PMID- 22293218 TI - Giant Seebeck coefficient thermoelectric device of MnO2 powder. AB - We report a giant Seebeck coefficient (S) thermoelectric (TE) material-MnO(2) powder-and the design of a practical MnO(2) TE generator to light up a regular light emitting diode (LED). The S of MnO(2) powder was measured to be higher than 20,000 MUV K(-1), which is about 100 times higher than the state-of-the-art of Bi(2)Te(3), one of the best TE materials. The giant S is very possibly closely related to the surface density of the electronic state (DOS), the Fermi energy level. The very high S and therefore high power factor is technologically important for transient TE cooling. PMID- 22293219 TI - Identification of three new variants of SDHx genes in a cohort of Portuguese patients with extra-adrenal paragangliomas. AB - BACKGROUND: Extra-adrenal paragangliomas (PGL) are rare neoplasms occurring in sporadic and familial forms, the latter mostly in association with germline mutations of SD- HB, SDHC or SDHD genes. AIM: Characterize frequency and spectrum of germline mutations among a cohort of Portuguese patients with extra-adrenal PGL. DESIGN: Molecular and clinical data were reviewed on 44 patients referred for genetic testing by a single laboratory. RESULTS: Genetic analysis identified 11 patients with head and neck PGL (30.6%) positive for SD- Hx gene mutations (6 SDHD, 4 SDHB, 1 SDHC) and 4 patients with abdominal or pelvic PGL (50%) positive for SDHx gene mutations (4 SDHB). Large deletions made up about 20% of the mutations detected. Mutation carriers were younger and more frequently had multiple or malignant PGL than patients without mutations. Only 11% of the head and neck PGL were secretory. In contrast, 100% of the abdominal or pelvic PGL were secretory. Five patients had a malignant PGL (4 SDHB, 1 apparently sporadic). Three novel mutations were identified: two in the SDHD gene (c.411delT [p.Leu139PhefsX29] and c.371_390del20insGG [p.Ala124_Ala130delinsGly]), one in the SDHB gene (c.49A>G [p.Thr17Ala]). The SDHD variant c.411delT [p.Leu139PhefsX29] was present in 3 apparently unrelated patients. Molecular genetic testing of 22 relatives disclosed 16 mutation carriers. CONCLUSIONS: Genetic analysis identified 15 patients (34.1%) and 16 at-risk individuals (72.7%) positive for SDHx gene mutations. The finding of three novel mutations broadens the mutational profile of the mitochondrial complex II succinate dehydrogenase genes reported in other large European series of patients with paragangliomas. Further studies are needed to clarify whether the high frequency of the SDHD variant c.411delT [p.Leu139PhefsX29] corresponds to a founder mutation. PMID- 22293220 TI - Mercury effects on Thalassiosira weissflogii: applications of two-photon excitation chlorophyll fluorescence lifetime imaging and flow cytometry. AB - The toxic effects of inorganic mercury [Hg(II)] and methylmercury (MeHg) on the photosynthesis and population growth in a marine diatom Thalassiosira weissflogii were investigated using two methods: two-photon excitation fluorescence lifetime imaging (FLIM) and flow cytometry (FCM). For photosynthesis, Hg(II) exposure increased the average chlorophyll fluorescence lifetime, whereas such increment was not found under MeHg stress. This may be caused by the inhibitory effect of Hg(II) instead of MeHg on the electron transport chain. For population growth, modeled specific growth rate data showed that the reduction in population growth by Hg(II) mainly resulted from an increased number of injured cells, while the live cells divided at the normal rates. However, MeHg inhibitory effects on population growth were contributed by the reduced division rates of all cells. Furthermore, the cell images and the FCM data reflected the morphological changes of diatom cells under Hg(II)/MeHg exposure vividly and quantitatively. Our results demonstrated that the toxigenicity mechanisms between Hg(II) and MeHg were different in the algal cells. PMID- 22293221 TI - Experimental reduction of food quality is not compensated with increased food intake in high-Arctic muskoxen (Ovibos moschatus). AB - A total of four barren adult female muskoxen (Ovibos moschatus) were used over a period of 2 years for the purpose of the present study. During the first year, the natural changes in appetite (ad libitum intake of standard pelleted reindeer feed) and body mass were determined in two of the animals. During the second year, the effect of reduced food quality on ad libitum food intake was tested in all four animals in July when the appetite had been found to be at a high. We found that the experimentally reduced food quality was not compensated with increased food intake in these large high-Arctic herbivores. PMID- 22293222 TI - The editor's roundtable: medical management of atrial fibrillation. PMID- 22293224 TI - Conquering atherosclerosis starts with improving medical education. PMID- 22293225 TI - Electrocardiogram in left ventricular hypertrabeculation/noncompaction. PMID- 22293226 TI - Long-term mortality and role of troponin elevation in hypertensive emergencies. PMID- 22293227 TI - Increased leukocyte Rho-associated coiled-coil containing protein kinase activity predicts the presence and severity of coronary vasospastic angina. AB - OBJECTIVE: Although inhibition of Rho-associated coiled-coil containing protein kinase (ROCK) has been shown to prevent coronary vasospastic angina (CVA), direct evidence linking ROCK activity and CVA is lacking. Accordingly, we investigated whether ROCK activity is an independent marker for CVA and is altered after treatment with antispastic medications. METHODS AND RESULTS: We prospectively studied 31 Taiwanese patients who were diagnosed with CVA and 33 control subjects. Subject demographics were recorded, and blood samples were obtained at baseline in all participants and in CVA patients after 3 months of antispastic treatment. Compared with control subjects, leukocyte ROCK activity was greater in CVA patients (136% versus 91%, P<0.001). A cutoff value for leukocyte ROCK activity of 104% predicted the presence of CVA with specificity and sensitivity rates of 88% and 84%, respectively. ROCK activity increased with the severity of CVA (P for trend<0.001). Following 3-month treatment of antispastic agents, leukocyte ROCK activity, high-sensitivity C-reactive protein, and interleukin-6 levels were reduced by 43%, 42% and 27%, respectively (P<0.05 for all). CONCLUSIONS: Increased levels of leukocyte ROCK activity independently predicted the presence of CVA and correlated with CVA severity. Treatment with antispastic agents substantially reduced the level of leukocyte ROCK activity. PMID- 22293228 TI - Sex-specific associations of serum prolactin concentrations with cardiac remodeling: longitudinal results from the Study of Health Pomerania (SHIP). AB - BACKGROUND: Previous experimental and patient-based studies suggest that prolactin (PRL) and its 16 kDa fragment influence cardiovascular phenotypes by modulating angiogenesis. The association between serum PRL and cardiac remodeling in the general population is unknown. METHODS: We evaluated 804 individuals (441 women) from the population-based Study of Health in Pomerania, aged >= 45 years, with available baseline serum PRL who underwent serial echocardiography at baseline and five-year follow-up. Left ventricular mass (LVM) was calculated and left ventricular hypertrophy (LVH) defined by sex-specific distributions of LVM. LV geometry was defined on the basis of relative wall thickness (RWT) and LVH. Sex-specific multivariable regression analyses were performed relating PRL (independent variable modelled as a continuous variable and as sex-specific quartiles) to change in LVM, RWT, and to incident LVH and abnormal geometry. RESULTS: Baseline PRL concentrations were inversely associated with LVM change in men, but not in women (beta per 10% decrease in PRL: 0.37; 95% CI, 0.13-0.60 in men and -0.02; 95% CI, -0.21 to 0.17 in women, respectively). In men, baseline PRL concentrations were also inversely associated with incident LVH [first vs. fourth PRL quartile: relative risk (RR) 2.26 (95% CI, 1.20-4.24)] and altered LV geometry on follow-up [RR for incident concentric hypertrophy per 10% decrease in PRL: 1.20 (95% CI, 1.06-1.37)]. None of the longitudinal associations were observed in women. CONCLUSION: We observed inverse associations of PRL with LVM change, incident LVH, and altered LV geometry in men, but not in women. Additional studies are warranted to confirm our findings and to elucidate the mechanisms underlying these sex-specific associations. PMID- 22293229 TI - Therapeutic potential of motor neurons differentiated from embryonic stem cells and induced pluripotent stem cells. AB - Degeneration of motor neurons (MN) caused by disease or injury leads to paralysis and is fatal in some conditions. To date, there are no effective treatments for MN disorders; therefore, cell therapy is a promising strategy to replace lost MN. Embryonic stem (ES) cells isolated from the inner cell mass of mammalian blastocysts self-renew and are pluripotent because they differentiate into cell types of the three germinal layers. Reprogramming of adult cells to a state similar to ES cells, termed induced pluripotent stem (iPS) cells, has been recently reported. It is well established that pluripotent cell types can give rise to specialized phenotypes, including neurons. Mouse, monkey and human MN can be differentiated from ES and iPS cells using procedures generally involving embryoid bodies formation and stimulation with retinoic acid and Sonic hedgehog. Differentiated MN express characteristic molecular markers such as Islet1, HB9 and Choline acetyltransferase, exhibit electrophysiological maturity and are able to form synaptic contacts similar to neuromuscular junctions in vitro. Furthermore, transplanted MN promote functional recovery in animal models of neurodegenerative diseases and MN injury. The potential clinical applications of stem cell-derived MN was enhanced after iPS cell derivation, which makes possible the generation of patient-specific pluripotent cells for autologous cell replacement therapies and may be used for drug development and disease modeling. This review summarizes MN differentiation protocols from ES and iPS cells in regard to neuronal differentiation efficiency, expression of MN markers and functional properties in vitro, as well as their therapeutic effects after grafting. PMID- 22293230 TI - Wish you were here! PMID- 22293231 TI - Development of sustained release floating drug delivery system for norfloxacin: in vitro and in vivo evaluation. AB - Norfloxacin is a drug with an absorption window. Its oral bioavailability is 30 40% and is a case for improvement by appropriate formulation design. In our previous study, gastroretentive floating tablets for norfloxacin were developed employing three different polymers such as HPMC K4M, HPMC K100M, and xanthan gum. The purpose of this investigation is to further improve and evaluate the in vitro and in vivo performance of the prepared floating tablets by inclusion of citric acid as an acidifier, which is also useful in a fed state. The prepared tablets were characterized and found to exhibit satisfactory physico-chemical characteristics. The effects of citric acid at different concentrations on drug release and floating properties were studied. All the prepared batches showed good in vitro buoyancy. It was observed that the tablets remained buoyant for 24 h. The best formulation (F4c), consisting of 1.5% citric acid and 18% HPMC K4M, was selected based on in vitro characteristics and used in vivo radiographic studies by incorporating barium sulphate. These studies revealed that the tablets remained in the stomach for 205 +/- 8.4 min in fasting human volunteers. In vivo studies were carried out for the best formulation in eight healthy male human volunteers, and the pharmacokinetic parameters of the developed formulation were compared with marketed conventional (Norbid) tablets. Based on the in vivo performance in a two-way, crossover study design in healthy subjects, the developed floating tablets showed superior bioavailability than the Norbid tablets. The increased bioavailability of developed formulation was found to be 16.27%. LAY ABSTRACT: Norfloxacin is a broad-spectrum antibiotic used to treat bacterial infections such as respiratory and urinary tract infections. Conventional norfloxacin tablets show incomplete drug absorption resulting in lower bioavailabilty. Norfloxacin is better absorbed in the stomach. The dosage forms that remain in the stomach are referred to as gastroretentive drug delivery systems. Gastroretentive floating tablets of norfloxcin were developed by employing three different polymers, which prolonged the drug release from the dosage forms. Tablet floatation was achieved by an effervescent mechanism. Citric acid at different concentrations was used in formulations to provide an acidic microenvironment. The prepared tablets were characterized for hardness, weight variation, thickness, friability, floating lag time, and dissolution. Around 12 tablet formulations were prepared as a continuation of the previous work. The best formulation (F4c) was selected based on in vitro characteristics and used in vivo radiographic studies by incorporating barium sulphate as a radio-opaque agent. The tablets remained in the stomach for about 205 +/- 8.4 min. Bioavailability studies were conducted in healthy male human volunteers, and the pharmacokinetic parameters of the best formulation were compared with that of the marketed conventional (Norbid) tablet. The increased bioavailability of the developed formulation was found to be 16.27%. PMID- 22293232 TI - Quality and integrity of data in research, development, and innovation: a risk analysis method applied to laboratory notebooks in a university pilot plant. AB - Risk analysis tools can be applied in the early stages of the research, development, and innovation of pharmaceutical drugs. We used a risk ranking and filtering method to optimize time resources in internal audits of project development documents in order to ensure traceability in a university pilot plant. Data gathered during audits undertaken over a 14 month period were classified according to risk factors at several levels. Consequently, time resources for this type of internal audit can be optimised by focusing on aspects that are objectively determined to be critical to traceability. In addition, quality can be ensured by paying more attention to the most critical aspects, rather than the most commonly observed findings in historical data. LAY ABSTRACT: One of the most important issue for a research, development, and innovation centre is the traceability of both experimental tasks and their documentation. This study describes an analysis of the findings revealed during internal audits carried out over a 14 month period, in order to establish its criticality and to highlight those important aspects to consider in future audits, while saving both personnel and time resources to carry out internal audits on development of projects. PMID- 22293233 TI - Risk analysis of sterile production plants: a new and simple, workable approach. AB - A sterile active ingredient plant and a sterile finished dosage filling plant both comprise very complex production processes and systems. The sterility of the final product cannot be assured solely by sterility testing, in-process controls, environmental monitoring of cleanrooms, and media fill validations. Based on more than 15 years experience, 4 years ago the authors created a new but very simple approach to the risk analysis of sterile plants. This approach is not a failure mode and effects analysis and therefore differs from the PDA Technical Report 44 Quality Risk Management for Aseptic Processes of 2008. The principle involves specific questions, which have been defined in the risk analysis questionnaire in advance, to be answered by an expert team. If the questionnaire item is dealt with appropriately, the answer is assigned a low-risk number (1) and if very weak or deficient it gets a high-risk number (5). In addition to the numbers, colors from green (not problematic) through orange to red (very problematic) are attributed to make the results more striking. Because the individual units of each production plant have a defined and different impact on the overall sterility of the final product, different risk emphasis factors have to be taken into account (impact factor 1, 3, or 5). In a well run cleanroom, the cleanroom operators have a lower impact than other units with regard to the contamination risk. The resulting number of the analyzed production plant and the diagram of the assessment subsequently offers very important and valuable information about a) the risk for microbiological contamination (sterility/endotoxins) of the product, and b) the compliance status of the production plant and the risk of failing lots, as well as probable observations of upcoming regulatory agency audits. Both items above are highly important for the safety of the patient. It is also an ideal tool to identify deficient or weak systems requiring improvement and upgrade, and delivers sound arguments for investments. Practical experience with this risk analysis, which has already been executed in several production sites in various countries, has demonstrated that it is simple, workable, and delivers valuable information. LAY ABSTRACT: Many important pharmaceutical products need to be sterile because they are to be injected into the patient's bloodstream or muscle. Sterile means that the product must be free of microorganisms (i.e., bacteria, yeast, and moulds). A non-sterile injection or infusion could lead to very serious or even lethal effects on the patient. Therefore one of the biggest challenges in the pharmaceutical industry nowadays is still the sterile production process itself. Microorganisms are everywhere in the environment, and humans are known to be a significant source of microbial contamination of a sterile product. It is necessary to set up a very effective quality assurance system as well as many quality control analysis tools to assure the sterility of the produced vials/syringes or of the bulk material intended for later filling into vials (bulk material, e.g., 10 kg in bags or cans). Above all, to get an accurate indication of the risk of non-compliance of product quality, regulatory agencies such as the U.S. Food and Drug Administration and the updated E.U. Good Manufacturing Practice (GMP) Guide have made it mandatory to perform a risk analysis of the production process. This provides in advance valuable information about the potential risk of a product's non-compliance with product specifications and GMP requirements, in our case regarding sterility. The authors set up a new approach for a risk analysis 4 years ago; this approach stems from fundamental experience gained over the past 15 years. Several specific questions are asked regarding various topics that correlate to the sterile production line and associated quality assurance/control systems. If the answer for an item is satisfactory and the best system is in place with regard to sterility, it is assessed with the prime rating of 1. If the topic is not satisfactory and very weak, the response is 5. Risk numbers from 2 to 4 are for intermediate situations. Because each unit of the production process could have a different type of impact of varying severity on the total product sterility, the average of the answers regarding the unit (e.g., 1, 2) is multiplied by the risk emphasis factor, which could be 1, 3, or 5. To make the rating even more distinct, colors are assigned from green (very good) through orange to red (very weak). There are currently three different risk analyses available for three different production processes. The results provide the users, that is, production personnel and quality assurance personnel, valuable feedback about the risk for possible non sterility in their process as well as sound arguments to present to management defending upgrades of their production line and control systems in the case of high numbers and red colors. Three years of implementation have demonstrated that this new risk analysis approach works and is very useful in identifying potentially risky components of a production process, thus preventing in advance the production of non-sterile product batches for the market, and finally protecting the patient from hazardous products. PMID- 22293234 TI - How risky are pinholes in gloves? A rational appeal for the integrity of gloves for isolators. AB - Isolators provide a high degree of protection for the product and/or the environment and operators in pharmaceutical production, as well as for analytical and sterility testing. Gloves allow for performing testing and for easy access to the process. Due to their nature-thin plastic, highly flexible-and their risk of puncture or rupture, they are regarded as one of the main potential sources of contamination. Glove integrity testing is therefore a main issue and has been addressed by many regulations such as those imposed by the USP, U.S. Food and Drug Administration, and Pharmaceutical Inspection Convention. This paper presents a short overview of different glove integrity test procedures and their ability to detect leaking gloves. Additionally, extensive microbiological tests have been performed to give more evidence and cross-correlation to physical testing. Most of the physical tests have limitations either in detecting pinholes and/or they are difficult to implement for routine testing. Microbiological tests are only applicable for evaluation and validation purposes, but not for routine testing, because they are time-consuming and do not allow immediate action. Routine visual verification of gloves by trained personnel turns out to be a very reliable technique. Additional microbiological tests supported by microbiological environmental monitoring helped to develop a new concept presented here on how to handle gloves with pinholes. It is proposed not to automatically consider a pinhole in a glove as a breach in isolator integrity, but to consider any action in view of controlling and monitoring the effective bioload on the outside of the gloves. With the combination of semi-automatic physical testing with independent protocol, visual inspection, and control of bioload through microbiological environmental monitoring potential contamination, risks can be minimized and maximum safety maintained. LAY ABSTRACT: Isolators are enclosure designs to protect critical handling and process steps in pharmaceutical environments. They provide a high degree of protection for product and/or environment and operators against particles, potentially hazardous active principles, and microbial load. Gloves mounted on windows and doors of the isolator allow for manipulation, performing testing, and access to the process. Due to their nature and their use with risk of puncture or rupture, they are regarded as a potential source for contamination. Glove integrity testing has therefor been addressed by regulations such as those imposed by the USP and the Food and Drug Administration. This paper presents a short overview of various glove integrity test procedures and their ability to detect leaking gloves. Most of the tests have limitations either in detecting pinholes and/or they are difficult to implement for routine testing. Routine visual verification of gloves by trained personnel turns out to be a very reliable technique. Additional microbiological tests led to a new concept presented here on how to handle gloves with pinholes and how to take action. With this approach, risks can be minimized and maximum safety maintained by controlling and monitoring the effective bioload on the outside of the gloves. PMID- 22293235 TI - Molecular applications to pharmaceutical processes and cleanroom environments. AB - This review article discusses several technologies using the power of genetic analysis that were used to rapidly detect microbial contamination, provide a more accurate identification of microorganisms, understand the microbial diversity in cleanroom environments, and optimize pharmaceutical processes. Nucleic acids were extracted and purified from enrichment cultures of product suspensions, growing cultures, microbial isolates, and directly from water and cleanroom surfaces. The extracted microbial DNA was either amplified using different polymerase chain reaction (PCR) assays or analyzed using DNA microarray technology. PCR assays were targeting genes coding for structural proteins, ribosomal subunits, or catabolic enzymes. Different PCR formats were tested ranging from single gene amplification to multiplexing. The detection of the amplified fragments was performed by qualitative or quantitative analysis. In some studies the amplified products were cloned/sequenced or sequenced to accurately determine the identity and diversity of the microbes present in the samples. DNA microarray analyses provided a higher multiplexing capability than PCR assays, as more than 3000 genes were analyzed in a single reaction, providing a higher resolution and specificity of the microorganisms present in cleanroom environments and pharmaceutical samples. LAY ABSTRACT: Molecular technologies using genetic sequences were used to rapidly detect microbial contamination, provide a more accurate identification of microorganisms, understand the types of microbes in pharmaceutical laboratories, and make pharmaceutical processes more efficient. The microbial genetic sequences were extracted from different types of samples. Then the extracted sequences were analyzed by looking for specific signatures to determine the identity and function of the different microbes in products, environments, and processes. Genetic analyses provided a better description of the different types of microbes present in pharmaceutical samples with a rapid quality evaluation of products and processes. PMID- 22293236 TI - Design-for-Six-Sigma for Development of a Bioprocess Quality-by-Design Framework. AB - An initial quality-by-design (QbD) framework was assembled for biopharmaceutical product, process, and analytical development using the design-for-six-sigma (DFSS) methodology. This technique was both streamlined and efficient, which permitted development of a QbD framework with minimized team leader and member resources. DFSS also highly emphasized voice-of-the-customer, information considered crucial to development and implementation of a bioprocess QbD framework appropriate for current development needs of the organization and its regulatory environment. The bioprocess QbD final design and implementation plan was comprised of seven teams, constructed from six QbD elements plus a communication/training team. Each element's detailed design was evaluated against internal and external established best practices, the QbD charter, and design inputs. Gaps were identified and risks mitigated to assure robustness of the proposed framework. Aggregated resources and timing were estimated to obtain vital implementation sponsorship. Where possible, existing governance and information technology efforts were leveraged to minimize additional bioprocess resources required. Finally, metrics were selected to track success of pilots and eventual implementation. LAY ABSTRACT: An initial quality-by-design (QbD) framework was assembled to guide biopharmaceutical product, process, and analytical development. QbD starts by defining the patient requirements which then are translated into required quality attributes for the product. The production process then is designed to consistently meet these quality requirements by identifying and understanding those parameters which influence them. A control strategy is developed that specifically relates each point of control to a desired quality measure. Overall, this approach results in a robust process, capable of reliably producing quality product. The bioprocess QbD framework was developed to guide implementation of the desired QbD strategy. It was comprised of seven teams, constructed from six QbD elements plus a communication/training team. Each element's detailed design was evaluated against internal and external established best practices, the charter, and design inputs. Gaps were identified and risks mitigated to assure robustness of the proposed framework. Aggregated resources and timing were estimated to obtain vital implementation sponsorship. Where possible, existing governance and information technology efforts were leveraged to minimize additional bioprocess resources required. Finally, metrics were selected to track success of pilots and eventual implementation. PMID- 22293237 TI - Excipients and their role in approved injectable products: current usage and future directions. AB - This review article is a current survey of excipients used in approved injectable products. Information provided includes concentration ranges, function, frequency of use, and role in dosage form. This article is an update of a paper published more than a decade ago (reference 11). Since then many new products have been approved. Safety concerning excipients has evolved as the scientific community continues to learn about their usage. New excipients are being used in early phases of clinical trials to support novel therapeutic entities like RNAi, aptamers, anti-sense, fusion proteins, monoclonal antibodies, and variant scaffolds. Because these excipients are not inert, various pharmacopoeias are responding with monographs or informational chapters addressing excipient functionality. The final sections of this article discuss new excipients, serving specific needs that traditional excipients are unable to provide and for which safety studies are necessary to support a novel excipient for marketing applications. LAY ABSTRACT: Excipients are added to parenteral dosage forms to serve a variety of functions including stabilization and as vehicles. This review article is a survey of excipients used in approved injectable products. Information provided includes excipient concentrations, functional roles, and frequency of use. This article is an update of an article originally published over a decade ago. Since then new products have been approved and safety concerns have evolved as the scientific community has learned about the usage of excipients. In addition, new excipients are being used in early phases of clinical trials to support novel therapeutic entities such as RNAi, aptamers, anti-sense, fusion proteins, monoclonal antibodies, and variant scaffolds. Because these excipients are not inert, various pharmacopoeias are responding with monographs or informational chapters addressing excipient functionality. The final sections of this article discuss new excipients, serving specific needs that traditional excipients are unable to provide and for which safety studies are necessary to support a novel excipient for marketing applications. PMID- 22293238 TI - Supercritical fluid technology: concepts and pharmaceutical applications. AB - In light of environmental apprehension, supercritical fluid technology (SFT) exhibits excellent opportunities to accomplish key objectives in the drug delivery sector. Supercritical fluid extraction using carbon dioxide (CO(2)) has been recognized as a green technology. It is a clean and versatile solvent with gas-like diffusivity and liquid-like density in the supercritical phase, which has provided an excellent alternative to the use of chemical solvents. The present commentary provides an overview of different techniques using supercritical fluids and their future opportunity for the drug delivery industry. Some of the emerging applications of SFT in pharmaceuticals, such as particle design, drug solubilization, inclusion complex, polymer impregnation, polymorphism, drug extraction process, and analysis, are also covered in this review. The data collection methods are based on the recent literature related to drug delivery systems using SFT platforms. SFT has become a much more versatile and environmentally attractive technology that can handle a variety of complicated problems in pharmaceuticals. This cutting-edge technology is growing predominantly to surrogate conventional unit operations in relevance to the pharmaceutical production process. LAY ABSTRACT: Supercritical fluid technology has recently drawn attention in the field of pharmaceuticals. It is a distinct conception that utilizes the solvent properties of supercritical fluids above their critical temperature and pressure, where they exhibit both liquid-like and gas-like properties, which can enable many pharmaceutical applications. For example, the liquid-like properties provide benefits in extraction processes of organic solvents or impurities, drug solubilization, and polymer plasticization, and the gas-like features facilitate mass transfer processes. It has become a much more versatile and environmentally attractive technology that can handle a variety of complicated problems in pharmaceuticals. This review is focused on different techniques that use supercritical fluids and their opportunities for the pharmaceutical sector. PMID- 22293239 TI - Intracellular protein delivery by hollow mesoporous silica capsules with a large surface hole. AB - We prepared cell membrane-permeable hollow mesoporous silica capsules (HMSCs) by a simple new method. CTAB micellar assembly in cholesterol emulsion gave rise to a novel capsular morphology of the HMSC particles. The HMSCs consisted of mesostructured silica walls with a large surface hole (25-50 nm) and the average particle dimension was 100-300 nm. They exhibited high surface areas of up to 719.3 m(2) g(-1) and a mesoporous range of pores of 2.4-2.7 nm. The surface functionalized HMSCs could also be prepared by a similar co-condensation method using tetraethoxysilane with various organoalkoxysilane precursors in the presence of cholesterol. These organically modified HMSCs could be further modified on demand. For example, a carboxy-functionalized HMSC could be surface functionalized by a green fluorescent 5-aminofluorescein (AFL) through an amidation reaction to afford a fluorescent AFL-HMSC. The hollow capsular morphology of the HMSCs with a large surface hole enabled us to develop very efficient intracellular delivery systems for membrane-impermeable ions, molecules, and various functional proteins. Non-covalent sequestration and delivery of proteins as well as covalent linkage of fluorescent molecules on the silica surface are effective for this system. The highly negatively charged green fluorescent probe mag-fluo-4 could be intracellularly delivered into HeLa cells by HMSC without any difficulty. The HMSCs could also effectively transport large functional proteins such as antibodies into HeLa cells. The efficiency of protein delivery by HMSC seems to be 3-22-fold higher than that of mesoporous silica nanospheres (MSNs) based on confocal laser scanning microscopy (CLSM) analysis. PMID- 22293240 TI - Is there any scientific evidence for the use of glucosamine in the management of human osteoarthritis? AB - Glucosamine in its acetylated form is a natural constituent of some glycosaminoglycans (for example, hyaluronic acid and keratan sulfate) in the proteoglycans found in articular cartilage, intervertebral disc and synovial fluid. Glucosamine can be extracted and stabilized by chemical modification and used as a drug or a nutraceutical. It has been approved for the treatment of osteoarthritis (OA) in Europe to promote cartilage and joint health and is sold over the counter as a dietary supplement in the United States. Various formulations of glucosamine have been tested, including glucosamine sulfate and glucosamine hydrochloride. In vitro and in vivo studies have uncovered glucosamine's mechanisms of action on articular tissues (cartilage, synovial membrane and subchondral bone) and justified its efficacy by demonstrating structure-modifying and anti-inflammatory effects at high concentrations. However, results from clinical trials have raised many concerns. Pharmacokinetic studies have shown that glucosamine is easily absorbed, but the current treatment doses (for example, 1,500 mg/day) barely reach the required therapeutic concentration in plasma and tissue. The symptomatic effect size of glucosamine varies greatly depending on the formulation used and the quality of clinical trials. Importantly, the effect size reduces when evidence is accumulated chronologically and evidence for the structure-modifying effects of glucosamine are sparse. Hence, glucosamine was at first recommended by EULAR and OARSI for the management of knee pain and structure improvement in OA patients, but not in the most recent NICE guidelines. Consequently, the published recommendations for the management of OA require revision. Glucosamine is generally safe and although there are concerns about potential allergic and salt-related side effects of some formulations, no major adverse events have been reported so far. This paper examines all the in vitro and in vivo evidence for the mechanism of action of glucosamine as well as reviews the results of clinical trials. The pharmacokinetics, side effects and differences observed with different formulations of glucosamine and combination therapies are also considered. Finally, the importance of study design and criteria of evaluation are highlighted as new compounds represent new interesting options for the management of OA. PMID- 22293241 TI - Can a standard dose of eicosapentaenoic acid (EPA) supplementation reduce the symptoms of delayed onset of muscle soreness? AB - BACKGROUND: Unaccustomed exercise can result in delayed onset of muscle soreness (DOMS) which can affect athletic performance. Although DOMS is a useful tool to identify muscle damage and remodelling, prolonged symptoms of DOMS may be associated with the over-training syndrome. In order to reduce the symptoms of DOMS numerous management strategies have been attempted with no significant effect on DOMS-associated cytokines surge. The present study aimed to investigate the acute and chronic effects of a 2 * 180 mg per day dose of eicosapentaenoic acid (EPA) on interleukin-6 (IL-6) mediated inflammatory response and symptoms associated with DOMS. METHODS: Seventeen healthy non-smoking females (age 20.4 +/ 2.1 years, height 161.2 +/- 8.3 cm and mass 61.48 +/- 7.4 kg) were randomly assigned to either placebo (N = 10) or EPA (N = 7). Serum IL-6, isometric and isokinetic (concentric and eccentric) strength, and rating of perceived exertion (RPE) were recorded on four occasions: i-prior to supplementation, ii-immediately after three weeks of supplementation (basal effects), iii-48 hours following a single bout of resistance exercise (acute training response effects), and iv-48 hours following the last of a series of three bouts of resistance exercise (chronic training response effects). RESULTS: There was only a group difference in the degree of change in circulating IL-6 levels. In fact, relative to the first baseline, by the third bout of eccentric workout, the EPA group had 103 +/- 60% increment in IL-6 levels whereas the placebo group only had 80 +/- 26% incremented IL-6 levels (P = 0.020). We also describe a stable multiple linear regression model which included measures of strength and not IL-6 as predictors of RPE scale. CONCLUSION: The present study suggests that in doubling the standard recommended dose of EPA, whilst this may still not be beneficial at ameliorating the symptoms of DOMS, it counter intuitively appears to enhance the cytokine response to exercise. In a context where previous in vitro work has shown EPA to decrease the effects of inflammatory cytokines, it may in fact be that the doses required in vivo is much larger than current recommended amounts. An attempt to dampen the exercise-induced cytokine flux in fact results in an over-compensatory response of this system. PMID- 22293242 TI - Does open-air exposure to volatile organic compounds near a plastic recycling factory cause health effects? AB - OBJECTIVES: After a plastic reprocessing factory began to operate in August 2004, the residents around the factory in Neyagawa, Osaka, Japan, began to complain of symptoms. Therefore, we conducted an exposure assessment and a population-based epidemiological study in 2006. METHODS: To assess exposure, volatile organic compounds (VOCs) and total VOCs were measured at two locations in the vicinity of the factory. In the population-based study, a total of 3,950 residents were targeted. A self-administered questionnaire was used to collect information about subjects' mucocutaneous or respiratory symptoms. Using logistic regression models, we compared the prevalence of symptoms in July 2006 by employing the farthest area from the factory as a reference, and prevalence odds ratios (PORs) and their 95% confidence intervals (CIs) were estimated. RESULTS: The concentration of total VOCs was higher in the vicinity of the factory. The prevalence of mucocutaneous and respiratory symptoms was the highest among the residents in the closest area to the factory. Some symptoms were significantly increased among the residents within 500 m of the factory compared with residents of an area 2800 m from the factory: e.g., sore throat (POR=3.2, 95% CI: 1.3-8.0), eye itch (POR=3.0, 95% CI: 1.5-6.0), eye discharge (POR=6.0, 95% CI: 2.3-15.9), eczema (POR=3.0, 95% CI: 1.1-7.9) and sputum (POR=2.4, 95% CI: 1.1-5.1). CONCLUSIONS: Despite of the limitations of this study, these results imply a possible association of open-air VOCs with mucocutaneous and respiratory symptoms. Because this kind of plasticre cycling factory only recently came into operation, more attention should be paid to the operation of plastic recycling factories in the environment. PMID- 22293243 TI - Evaluation of workers exposed to ethylene glycol monomethyl ether and ethylene glycol monomethyl ether acetate. AB - OBJECTIVES: Ethylene glycol monomethyl ether (EGME) and ethylene glycol monomethyl ether acetate (EGMEA) are widely used in industries as solvents for coatings, paint and ink, but exposure data are limited because they are minor components out of mixed solvents, as well as because of inconsistency in desorption solvent use. The objective of this study was to investigate the worker exposure profile of EGME and EGMEA. METHODS: Our study investigated 27 workplaces from June to September 2008 and detected EGME and EGMEA in 20 and 13, respectively. Both personal and area sampling were conducted using a charcoal tube to collect EGME and EGMEA. Gas chromatography with a flame ionization detector was used to analyze these compounds after desorption using a mixture of methylene chloride and methanol. RESULTS: The arithmetic mean concentrations of EGME and EGMEA during periods of full work shifts were 2.59 ppm and 0.33 ppm, respectively. The exposure levels were lower than the Korean Ministry of Labor (MOL) OEL (5 ppm) but higher than the ACGIH TLV (0.1 ppm). CONCLUSIONS: In general, the working environments were poor and required much improvement, including the use of personal protective equipment. Only 50% of the workplaces had local exhaust ventilation systems in operation. The average capture velocity of the operating local exhaust ventilation systems was 0.27 m/s, which did not meet the legal requirement of 0.5 m/s. Educating workers to clearly understand the handling and use of hazardous chemicals and improving working conditions are strongly suggested. PMID- 22293244 TI - Adverse psychosocial working conditions and poor quality of life among financial service employees in Brazil. AB - OBJECTIVES: Workers in the financial services sector are exposed to great stress at work. This study investigates whether exposure to adverse psychosocial work conditions is independently associated with poor health-related physical and mental quality of life among financial services workers. METHODS: We studied a nationwide representative sample of 2,054 workers of a large Brazilian state bank in 2008. Adverse psychosocial work conditions were investigated by the Effort reward imbalance (ERI) scale and the Job content questionnaire (JCQ). Health related quality of life (HRQL) was assessed using the Medical Outcomes Study Short-Form General Health Survey (SF-12). Poor mental and physical HRQL was defined by the lowest quartiles of the SF-12 final score distributions. Associations were investigated using multiple logistic regression analysis. RESULTS: In the multivariate analysis, exposures to low control and lack of social support at work (JCQ) were associated with poor HRQL in the physical domain. Increasing effort-reward imbalance and overcommitment (ERI), on the other hand, were associated with poor HRQL in the mental domain, with a significant statistical trend. Overcommitment was also associated with poor physical HRQL. CONCLUSION: The results suggest that exposure to adverse psychosocial work conditions has a negative impact on both domains of HRQL among financial service workers. They also indicate that ERI and DC models capture different aspects of job strain. PMID- 22293245 TI - A longitudinal study on Raynaud's phenomenon in workers using an impact wrench. AB - OBJECTIVES: The purpose of this study was to clarify the occurrence of Raynaud's phenomenon among workers using an impact wrench for a long time. METHODS: The subjects were 704 workers regularly using an impact wrench and taking special medical examinations for vibration syndrome from 1981 to 2008. Raynaud's phenomenon was observed in 39 subjects during the observation period. RESULTS: The mean operating years at the occurrence of Raynaud's phenomenon was 25.5 +/- 8.3 (standard deviation) yr. The mean total operating time (geometric average) at the occurrence of Raynaud's phenomenon was 11,689 h. By the person-year method, the incidence rate of Raynaud's phenomenon was 6.27 persons per 1,000 person years. The estimated risk of developing Raynaud's phenomenon did not increase until 12 years after starting to operate an impact wrench but increased exponentially after that. The vibration level of an impact wrench (from 4.9 m/s(2) to 22.6 m/s(2)) exceeded the occupational exposure limit value (4.9 m/s(2)). Various countermeasures, such as introducing automatically apparatus and keeping the working environment warm to protect from cold exposure, were taken at the factory. CONCLUSIONS: These findings showed that the rate of occurrence of Raynaud's phenomenon was not high, although the vibration level of the impact wrench was high. This may result from various countermeasures to prevent the occurrence of Raynaud's phenomenon. A long period of exposure to vibration had the potential to lead to the occurrence of Raynaud's phenomenon even under various countermeasures. PMID- 22293246 TI - Impact of chronic diseases on work ability in ageing firefighters. AB - OBJECTIVES: The aim of this study was to study the impact of chronic diseases on work ability in different age groups of Dutch firefighters. METHODS: Firefighters filled out a questionnaire about the presence of nine types of chronic diseases and rated their current work ability (0 unable to 10 best ever). The differences in work ability in firefighters in total and in four age groups with and without chronic diseases were calculated with a Fisher's exact test. RESULTS: Of 276 firefighters 23% reported having a chronic disease, with the rate varying among the age groups between 18 and 41%. Median work ability was 8, varying between 7 and 8 in the age groups. No significant difference was found in work ability for firefighters with and without chronic diseases, independent of the age groups. CONCLUSIONS: Having a chronic disease is not associated with a significantly lower self-reported work ability estimate in firefighters. PMID- 22293247 TI - Recurrent and persistent cytomegalovirus infection in a kidney recipient caused by the L595S mutation in UL97 phosphotransferase gene. AB - Ganciclovir (GCV) is the first therapeutic choice for prevention and treatment of active cytomegalovirus (CMV) infection in solid organ transplant recipients in Bahia state, Brazil. Prolonged and repeated GCV therapy may result in drug resistant virus, associated with progressive and disseminated disease. We present a case report of a young male kidney recipient, who was CMV-seronegative with a CMV-seropositive donor (D(+)/R(-)), and who developed clinical GCV resistance, confirmed by mutation in viral UL97 phosphotransferase responsible for GCV activation. Under prophylactic therapy with intravenous GCV for 6 weeks post transplantation, he developed severe anaemia and hepatic enzyme increases, probably due to drug side effects. At this moment, the drug was discontinued and he started to be monitored by pp65 antigen test. At week 10 post-transplantation, he presented fever, myalgia, thrombocytopenia and neutropaenia, with a positive CMV antigen test. During treatment with intravenous GCV, antigenaemia assay demonstrated a higher number of positive cells, requiring GCV at higher doses. Pre-emptive therapy lasted for 31 days and he started the maintenance therapy with oral GCV. However, antigenaemia assay demonstrated an extremely high number of positive cells, and he was rehospitalized and prescribed intravenous GCV. Severe leukopaenia led to GCV interruption, but immunosuppressive dose reduction helped to control the active CMV infection. GCV-resistant CMV infection resulted in increased morbidity, rehospitalization episodes and increased costs; therefore, implementation of resistance diagnostic tests in the transplantation routine is of great importance. We documented the first case of GCV-resistant CMV infection due to the L595S mutation in UL97 phosphotransferase gene in a kidney recipient from Bahia state, Brazil. PMID- 22293248 TI - Paradigm shift in surgery for breast cancer: the Indian reality. PMID- 22293249 TI - Estrogen, progesterone and HER2 receptor expression in breast tumors of patients, and their usage of HER2-targeted therapy, in a tertiary care centre in India. AB - BACKGROUND: This study was undertaken to document the pattern of expression of estrogen (ER), progesterone (PR) and human epidermal growth factor receptor-2 (HER2) and the usage of HER2-targeted therapy in a large tertiary care hospital in India in the year 2008. MATERIALS AND METHODS: The histopathology reports of all breast cancer patients registered in the hospital in 2008 were extracted from the electronic medical record system. All the cases were immunohistochemically evaluated for estrogen and progesterone receptor status (ER and PR), and c-erbB-2 protein (HER2) expression using standard immunoperoxidase method. The use of HER2 targeted therapies was evaluated by extracting relevant information from the database of the hospital pharmacy and case charts of patients enrolled in ongoing approved trials. RESULTS: A total of 2001 new patients of invasive breast cancers with available pathology reports were registered in the hospital in the year 2008. ER and/or PR expression was positive in tumors of 1025 (51.2%) patients. HER2 3+ expression by immunohistochemistry (IHC) was found in 335 (16.7%) and HER2 2+ in 163 (8.1%). The triple negative phenotype was found in 596 (29.8%) patients. An estimated 441 patients were eligible to receive HER2-targeted therapy based on their HER2 status. Of these 38 (8.6%) patients received some form of HER2-targeted therapy; 20 patients (4.5%) as part of ongoing clinical trials and 18 (4.1%) as part of routine care. CONCLUSIONS: The overwhelming majority of patients eligible for HER2-targeted therapy in our institution are unable to receive it because of financial constraints and limited access to health insurance. There is a higher fraction of patients with the triple negative phenotype compared to the Western population. PMID- 22293250 TI - Comprehensive decongestive therapy in postmastectomy lymphedema: an Indian perspective. AB - BACKGROUND: Lymphedema following breast cancer treatment is one of the most morbid conditions affecting breast cancer survivors. Currently, no therapy completely cures this condition. Comprehensive Decongestive Therapy (CDT), a novel physiotherapeutic method offers promising results in managing this condition. This therapy is being widely used in the West. Till date, there are no studies evaluating the effectiveness and feasibility of this therapy in the east. MATERIALS AND METHODS: The therapeutic responses of 25 patients with postmastectomy lymphedema were analyzed prospectively in this study. Each patient received an intensive phase of therapy for eight days from trained physiotherapists, which included manual lymphatic drainage, multi layered compression bandaging, exercises, and skin care. Instruction in self management techniques were given to the patients on completion of intensive therapy. The patients were followed up for three months. Changes in the volume of the edematous limb were assessed with a geometric approximation derived from serial circumference measurements of the limb and by water displacement volumetry. Changes in skin and sub cutis thickness were assessed using high frequency ultrasound. RESULTS: The reduction in limb volume observed after therapy was 32.3% and 42% of the excess, by measurement and volumetry, respectively. The maximum reduction was obtained after the intensive phase. The reduction in skin and subcutis thickness of the edematous limb followed the same pattern as volume reduction. Patients could maintain the reduction obtained by strictly following the protocols of the maintenance phase. CONCLUSIONS: CDT combined with long-term self management is effective in treating post mastectomy lymphedema. The tropical climate is a major factor limiting the regular use of bandages by the patients. PMID- 22293251 TI - Is locally advanced breast cancer a neglected disease? AB - BACKGROUND AND AIMS: Breast cancer is the second most common malignancy in India, and majority of patients present as a locally advanced breast carcinoma (LABC). Evaluating the prevalence of LABC and assessing the causes of local advancement and delayed presentation is the aim of the present study. SETTINGS AND DESIGN: This was a rural hospital-based prospective cross-sectional study. STATISTICAL ANALYSIS: Descriptive statistics. MATERIALS AND METHODS: Seventy-one cytologically/histopathologically confirmed cases of breast carcinoma were enrolled in the study. Breast sarcomas and lymphoma were excluded and, of them, prevalence of LABC and causes of delay and local advancement, i.e. patient factors, system factors and biological factors, were evaluated. RESULTS: LABC accounted for 50.7% of these patients. On assessing the cause of advancement of LABC, patient factor (69.8%) was the major cause for delayed presentation, followed by system delay (23.6%). Patient factors were lack of awareness of breast cancer (75%) and financial constraints (52.8%). The system factor was nonreferral by general practitioners to specialty centers or trying to treat these patients with other allied modalities of treatment. CONCLUSIONS: LABC in the Indian scenario is an outcome of neglect due to patient and system factors. These factors offer an excellent opportunity to plan a community-oriented preventive strategy for the general population and practitioners to decrease the incidence of LABC. PMID- 22293252 TI - Age pattern of the occurrence of breast cancer in the northwest of Iran. AB - Breast cancer represents 27% of the cancers and 19% of the cancer deaths in female population. The aim of this study was to document the age pattern of the incidence of breast cancer in Iranian female population in the northwest region of the country. The study subjects were 1764 patients with breast cancer diagnosed/registered in the six university clinics between 1988 and 2008 in the northwest of Iran. The highest occurrence rates were observed for the birth year cohorts 1940-1949 (for 59-69 years old), 1950-1959 (for 49-58 years old), and 1960-1969 (for 39-48 years old). Among these three cohorts, the highest rate was observed in 1950-1959 birth year cohort (284.38 per 100,000 female populations, 95% CI: 260-310). This rate was significantly higher compared with the similar rates of other birth cohorts. There was no statistically significant difference between various years in terms of the average age at the diagnosis of breast cancer in our study setting. Despite the previous research reports, we found no significant difference between the mean ages at diagnosis of breast cancer from 1988 to 2008 in Iranian female population. PMID- 22293253 TI - Clinical and pathological response rates of docetaxel-based neoadjuvant chemotherapy in locally advanced breast cancer and comparison with anthracycline based chemotherapies: eight-year experience from single centre. AB - INTRODUCTION: The administration of neoadjuvant chemotherapy (NACT) prior to local therapy is advantageous for women with locally advanced breast cancer (LABC), since it can render inoperable tumors resectable and can increase rates of breast conservative surgeries. MATERIALS AND METHODS: We retrospectively analyzed LABC patients who received NACT from January 2000 to December 2007. Out of 3000 case records screened, 570 (19%) were LABC and 110/570 (19%) treatment naive patients started on NACT were analyzed. Ninety-one (37 docetaxel [D], 54 anthracycline [A]) patients were eligible for response and survival analysis. Pathological complete remission (pCR) was defined as no evidence of malignancy in both breast and axilla. RESULTS: Median age of the whole cohort was 45 years (range 25-68 years). Premenopausal were 42% and estrogen receptor + 49.5%. Most (90%) were T4 tumors and 70% were Stage IIIB. Median numbers of preoperative cycles were six and three in the D and A group respectively. Overall clinical response rates for breast primary were 74.3% and 53.7% (CR 28.6% vs. 16.7%, P=0.58) while for axilla ORR were 75.7% vs. 54.8% (51.4% vs. 40.4% CR, P=0.77) respectively for D and A. Corresponding pCR rates were 19% vs. 13% respectively. There was no significant difference in disease-free (three-year 56.84% vs. 61.16%, P=0.80) and overall survival (three-year 70% vs. 78.5%, P=0.86) between the two groups. CONCLUSIONS: Although pCR rates were higher with docetaxel-based NACT, it did not translate into superior disease-free survival / overall survival compared to anthracycline-based chemotherapies. PMID- 22293254 TI - Breast conserving surgery for breast cancer: single institutional experience from Southern India. AB - CONTEXT: In India, breast conservation rates vary anywhere from 11 to 34%. This is in contrast to western world where breast conservation rates exceed 70% for early breast cancer. AIMS: The present study was conducted to analyze the results of breast conservation surgery (BCS) at our institute and compare with that of other facilities in world. SETTINGS AND DESIGN: The study was a prospective, outcome analysis study. All patients who underwent BCS were included. Data pertaining to clinical, pathological characteristics and treatment related outcomes were recorded. MATERIALS AND METHODS: The study comprised of retrospective collection of prospective data of 88 patients who underwent breast conservation treatment (BCT) till December 2009. STATISTICAL ANALYSIS USED: The statistical analysis included Kaplan-Meier survival analysis for disease-free (DFS) and overall survivals (OS), and univariate analyses to assess each prognostic factor separately using SPSS 16.0 for windows. RESULTS: Most common tumor location was upper outer quadrant and most common histology was infiltrating duct carcinoma. Median age was 45 years. Eighteen patients received preoperative chemotherapy to conserve the breast. Pathological complete response (pCR) in this subgroup was 39%. Majority had node negative disease and 42 tumors were hormone receptor positive. Median follow-up was 49 months. Two patients developed isolated local recurrences which were salvaged surgically. Seven patients had systemic disease of which 5 had simultaneously failed locally. Overall 5-year DFS was 89 %. CONCLUSIONS: When given an option, patients with breast cancer do desire to conserve their breast. PMID- 22293255 TI - Opinion of nurses regarding breast cancer screening programs. AB - AIM: Found to be effective in its treatment. The increased incidence of breast cancer supports the implementation of breast cancer screening programs. The present study evaluates the opinion among nurses regarding breast cancer screening programs in United Arab Emirates (UAE). MATERIALS AND METHODS: The study population included 154 nurses practicing at different hospitals in United Arab Emirates (UAE), all nurses who participated in the breast cancer awareness programme organized by Gulf Medical University, Ajman, UAE. A self-administered, pretested, structured, close-ended questionnaire was used for data collection. Statistical Analysis was performed using Predictive Analytic Software (PASW 17). RESULTS: The participants' age ranged between 20 and 59 years. Fifty percent of the participants strongly agreed with the early detection of breast cancer by performing breast self examination. Thirty-nine percent were of the opinion that women aged 40 years and older should have a mammogram every year and continue to do so and 25.3% strongly felt that women in their 20s and 30s should have clinical breast examination as part of their periodic health examination by health professionals. 33.8% of the respondents strongly agree on providing information on the benefits and limitations of BSE to the female population. Twenty-six percent of the participants strongly agree that women at high risk should get magnetic resonance imaging and mammogram done every year. CONCLUSION: The present study indicates the need for providing workplace training programs thus equipping them with better knowledge and enhancing their service among the general population. PMID- 22293256 TI - Expenditure audit of women with breast cancer in a tertiary care hospital of Delhi. AB - BACKGROUND: Breast cancer is associated with substantial medical and economic burden. This study assisted the expenditure incurred by the subjects on diagnosis and treatment till the period of follow-up. MATERIALS AND METHODS: This is a prospective study; a case series of patients studied at the time of diagnosis and followed after 6 months. The study was conducted at one of Hospitals in India, from January 2006 to December 2007. One hundred and seventy-two women with new primary breast cancer were included in the study. During the study period 69 subjects were lost to follow-up. The comparative analysis was done for 103 subjects. Cost implications of breast cancer include direct medical costs and indirect costs. Questionnaire for the data collection was used. Descriptive statistics and correlation analysis were used. RESULTS: The median total direct and indirect expenditure was Rs. 12,100 (US$ 1 = Rs 50) with the range of Rs. 0 54000. The largest component of total direct medical costs was in stage I (median Rs. 6530), total indirect costs (median Rs. 7500), and median total cost was Rs. 17,600. The total expenditures (median Rs. 13,100) were the highest in younger age group (<40). The median direct expenditure was higher in the subjects who visited private setup before coming to Hospital (Rs. 8250) than those who came directly (Rs. 4500). CONCLUSIONS: Cost of treatment for breast cancer depends on many factors, including the stages of the cancer, the woman's age, perhaps the costs of treatment, private hospital and insurance. PMID- 22293257 TI - Nilotinib as first-line therapy for chronic myeloid leukemia. AB - Tyrosine Kinase Inhibitors brought a revolution in the management of chronic myeloid leukemia. Long term disease free survival became a reality for the majority of patients. With the identification of imatinib resistance and its implications, roles of newer targeted therapy molecules came into focus. Nilotinib data has matured and shows the fulfillment of earlier promise - even in first line therapy. This review provides insight into the place of this molecule in the first line management of chronic myeloid leukemia. PMID- 22293258 TI - Malignant lymphoma in northern Iraq: a retrospective analysis of 270 cases according to the World Health Organization classification. AB - BACKGROUND: Based on the World Health Organization (WHO) classification, the distribution of various subtypes of malignant lymphoma (ML) appears to differ by geographical region. AIMS AND DESIGN: studying the patterns of ML retrospectively in a previously uncharted country (Iraq) and to compare it with patterns observed regionally and worldwide. MATERIALS AND METHODS: Two hundred and seventy lymphoma patients referred to two major histopathology referral centers in Northern Iraq, were categorized according to the WHO classification, using morphology and appropriate immunohistochemistry. RESULTS: There were 205 (76%) non-Hodgkin lymphomas (NHL) and 65 (24%) Hodgkin lymphomas (HL). Of the NHL, 91% were B-cell and 9% T-cell. The most common NHL was Diffuse large B-cell lymphoma (DLBCL) which comprised 52.2% of NHL, followed by Burkitt's lymphoma (BL) at 14.6%. The latter were mostly intestinal primaries. While follicular lymphomas (FL) were infrequent constituting 2.9 % of NHL. Extranodal primaries were found in 48.3% of NHL. Hodgkin's lymphoma (HL) included 48% nodular sclerosis (NS) and 37% mixed cellularity (MC). All HL were nodal primaries. CONCLUSIONS: Among NHL, the high frequencies of DLBCL, extra nodal primaries and intestinal BL, and the infrequency of FL in northern Iraq, is similar to reports from nearby countries but differs considerably from the West and Far East, indicating a shared regional Middle East influence on non-Hodgkin lymphoma patterns. In contrast to earlier Iraqi and regional studies on HL, NS has surpassed MC as the most frequent histological subtype in Northern Iraq. This trend probably reflects the increasing urbanization that has taken place in this region. PMID- 22293259 TI - Can Carboplatin replace Cisplatin in small cell lung cancer? PMID- 22293260 TI - Carboplatin plus etoposide for extensive stage small-cell lung cancer: an experience with AUC 6 doses of carboplatin. AB - AIMS: The aim of this study is to investigate the activity and toxicity of etoposide with AUC 6 doses of carboplatin in patients with previously untreated extensive disease - small-cell lung cancer (SCLC). MATERIALS AND METHODS: 88 eligible patients were treated with chemotherapy comprised of carboplatin AUC of 6, IV day 1 and etoposide 100 mg/m 2 , IV day 1-3. This schedule was repeated every 21 days for maximum of six cycles. RESULTS: Patients characteristics: Median age, 62 years; 84 male; ECOG PS 0-1 in 73 patients, PS 2-3 in 15 patients. A total of 431 cycles were administered (median, 6.0). The complete and partial response rates were 23.9% and 45.5%, respectively. Median overall survival (OS) was 9.0 months (95% confidence interval [CI], 8.09 - 9.90 m); 84 patients died. The 1- and 2-year survival probabilities were 33.6% and 5.3%, respectively. The median progression-free survival in patients of 65 was 7.2 months (95% CI, 5.81 - 8.58), 12-month PFS rate was 10%. The median OS was 11.6 months (95% CI, 8.52 - 14.67 m) and 7.5 months (95% CI, 5.61 - 9.38 m) in patients with non-liver and liver metastasis, respectively (P = 0.024). The median OS was 9.3 months (95% CI, 7.83 - 10.76 m) and 7.5 months (95% CI, 5.58 - 9.44 m) in patients with single and multiple distant metastasis, respectively (P = 0.02). Grade 3-4 neutropenia, thrombocytopenia, and anemia were detected in 57.9%, 15.9%, and 11.4% of patients, respectively. Febrile neutropenia was developed in 12 patients. CONCLUSION: Etoposide with AUC 6 doses of carboplatin is active and tolerable in patients with extensive disease - SCLC. PMID- 22293261 TI - FOLFOX (oxaliplatin and 5 fluorouracil/leucovorin) in patients with untreated metastatic gastric adenocarcinoma Phase II study. AB - BACKGROUND: Oxaliplatin has shown promising activity in metastatic gastric cancer (MGC) and has synergism with 5 fluorouracil. This phase II study was performed to evaluate the efficacy and safety of FOLFOX4 regimen in MGC. MATERIALS AND METHODS: Patients with MGC, aged 18-70 years, performance status <=2, no prior chemotherapy, received FOLFOX4 regimen every 2 weeks as oxaliplatin 85 mg/m 2 IV infusion on day 1 and leucovorin 200 mg/m 2 IV infusion followed by fluorouracil 400 mg/m 2 IV bolus and 600 mg/m 2 22-hour continuous infusion on days 1 and 2. Treatment was administered until progression, unacceptable toxicity, patient's refusal or for a maximum of 12 cycles. RESULTS: From August 2007 to June 2010, 34 patients were prospectively enrolled. The median age was 52 years (28-69). In total, 293 cycles were administered with a median of 8 cycles per patient (range 1-12 cycles) and 33 of 34 patients were assessable for treatment response. The overall response rate were 53% with one patient(3%) had complete response, 17 patients (50%) had partial responses and 6 patients (18%) had stable disease. The median survival of all patients was 12.1 months and the median time to progression was 9.4 months. The most common grade 3/4 toxic effects were neutropenia in four patients (12%), diarrhea in three patients (9%), vomiting in two patients (6%) and peripheral neuropathy occurred in three patients (9%). CONCLUSIONS: The FOLFOX4 combination chemotherapy showed a very promising antitumor activity and was generally well-tolerated as a first-line treatment of patients with MGC. PMID- 22293262 TI - Clinicopathologic spectrum of gastro intestinal stromal tumours - experience at a tertiary care center. AB - CONTEXT: Accurate diagnosis of Gastrointestinal stromal tumors (GISTs) and categorization of risk groups is crucial in the wake of targeted drug therapy. AIM: This study was undertaken to obtain insight into the clinicopathologic features of GISTs. MATERIALS AND METHODS: Retrospective study of 20 cases of c KIT (CD 117) positive GISTs .Various histologic parameters were studied. Immunohistochemical panel included CD-34, Smooth muscle actin, S-100, Desmin, and Vimentin. Risk categorization was done as per standard protocol. Clinical details and follow up were retrieved from cases files. RESULTS: Of the total 20 cases, 15 were males. The mean age of presentation was 52 years. 50 % of the cases presented with gastro intestinal bleeding. The cases were categorized as high risk (60%), intermediate risk (20%), low risk (15%) and very low risk (5%). Stomach and small intestine were commonly involved and in 6 of the cases there were metastatic nodules in the mesentery/omentum/ peritoneum. Spindle cell morphology was the commonest histological pattern (55%). Nuclear pleomorphism, perivascular whorling, mucosal and fat invasion were seen only in the high risk group. CD-34, SMA and S-100 were positive in 90%, 30%, and 10% of the cases, respectively, with consistent Desmin negativity. CONCLUSIONS: Cases of GISTs in our clinical setting presented a decade earlier and mostly belonged to the high risk group. Certain histological features such as necrosis, and perivascular whorling were more commonly associated with the high risk groups. PMID- 22293263 TI - Is hysterectomy needed in ovarian cancer? AB - CONTEXT: Hysterectomy is an integral part of ovarian cancer surgery. The authors have evaluated the uterine involvement in ovarian cancer in this study. AIMS: Conventionally, removal of the uterus is considered an essential part of ovarian cancer surgery, but rationale for same in absence of its gross involvement is questionable. Aim of this study was to evaluate the microscopic involvement of uterus in ovarian cancer and whether there are any predictors of uterine involvement. SETTINGS AND DESIGN: Retrospective study. MATERIALS AND METHODS: The authors analyzed 128 patients of epithelial ovarian cancer (EOC) operated from 2004 January to 2008 June, who had not undergone hysterectomy previously. Data regarding their demographic, clinical, and pathological findings was collected and analyzed. STATISTICAL ANALYSIS USED: Chi-square test. RESULTS: Most of our patients (n=111) presented with stage III or above. Serous carcinoma was the most common histology encountered (86.7%). Uterus was grossly involved in only 19 patients and microscopic involvement was noted in 20 patients. Only one patient with absence of gross involvement had microscopic disease in the uterus. Involvement of the uterus was found to be independent of stage, type of tumor, laterality, and preoperative chemotherapy. The grade of tumor and gross uterine involvement were only factors that showed statistically significant correlation with microscopic uterine involvement. Only one patient had synchronous endometrial cancer. CONCLUSIONS: Uterine involvement in EOC is not common. Absence of gross uterine involvement reliably predicts absence of microscopic disease. PMID- 22293264 TI - Perceptions and concerns of women undergoing Pap smear examination in a tertiary care hospital of India. AB - BACKGROUND: Cervical cancer is one of the major causes of deaths due to cancer among women in India. Pap smear is one of the best methods to detect early changes in cervix. However, there is lack of data on awareness level of women about Pap smear and various risk factors for cervical cancer. OBJECTIVES: To study the awareness about various risk factors for cervical cancer, health seeking behavior and hygienic practices among women and to assess the distress experienced by these women before the Pap smear examination. MATERIALS AND METHODS: This cross-sectional study was carried out on women coming for a Pap smear examination in a tertiary teaching hospital in New Delhi. A pretested interview schedule was used to get information after obtaining their informed consent. RESULTS: Fifty-seven percent stated that they did not consult a doctor when they noticed the symptoms the first time. Sixty-one percent did not know what a cervical cancer is and a same percentage of women did not know what a Pap smear examination was. Older age group, Muslim and literate women had higher number of abnormal Pap smear results. Women who reported being stressed in their lives had higher number of abnormal smears as compared to women who claimed to lead a stress free life. Poor hygienic practices among these women from urban areas were also associated with abnormal Pap smear results. CONCLUSION: The study concluded that factors such as poor awareness, shyness, poor hygiene, and old age could be responsible for abnormal Pap smears and this needs special attention in cancer prevention activities of the government. PMID- 22293265 TI - Correlation between the preoperative serum prostate specific antigen, Gleason score, and clinical staging with pathological outcome following robot-assisted radical prostatectomy: an Indian experience. AB - OBJECTIVES: To correlate the preoperative serum prostate specific antigen (PSA), Gleason score, and clinical staging with pathological outcome following robot assisted radical prostatectomy (RARP) in Indian men with clinically localized cancer prostate. MATERIALS AND METHODS: A prospective study analysis was done for 166 consecutive patients of prostate cancer who underwent RARP at our center from June 2006 to October 2009. Preoperative workup included serum PSA, biopsy Gleason score, and clinical staging. The preoperative parameters were correlated with final Gleason score, capsular penetration, seminal vesicle involvement, and lymph node status on final histopathology. RESULTS: The mean age was 64 years (range: 50-76 years) with mean and median PSA of 17.98 ng/ml (range: 0.3-68.3 ng/ml) and 12.1 ng/ml, respectively. With increase in preoperative Gleason score, chance of organ confinement decreases (P=0.002) and capsular penetration increases (P=0.004) linearly. With increasing serum PSA, there is linear decrease in trend of organ-confined disease (P=0.03) and increased chances of seminal vesicle involvement (P=0.02). Patients with higher clinical stage have less probability of localized disease (P=0.007) and more chances of capsular penetration (P=0.04) and seminal vesicle involvement (P=0.004). CONCLUSION: Our data suggest that patients with higher preoperative serum PSA, Gleason score, and clinical stage have more chances of advanced pathological stage following RARP. PMID- 22293266 TI - Interobserver reproducibility of Gleason grading of prostatic adenocarcinoma among general pathologists. AB - CONTEXT: Gleason grade is the most widely used grading system for prostatic carcinoma and is recommended by World Health Organization. It is essential that there should be good interobserver reproducibility of this grading system as it has important implications in patient management. AIM: To assess interobserver reproducibility of Gleason grading of prostatic adenocarcinoma. DESIGN: A total of 20 cases of prostatic adenocarcinoma were scored using Gleason grade by 21 general pathologists. The scores were then compared using kappa-coefficient and consensus score. RESULTS: For Gleason score groups (2-4, 5-6, 7 and 8-10) overall agreement with consensus score was 68%. Exact agreement for Gleason scores with consensus score was 43.3% and 92.3% within +/-1 of the consensus score. kappa coefficient for primary grade ranged from -0.32 to 0.92 with 60% of the readings in fair to moderate agreement range; and for secondary grade kappa ranged from 0.30 to 0.62 with 78% of the readings in slight to fair agreement range. Kappa for Gleason scores ranged from -0.13 to 0.55 with 80% of the readings in slight to fair agreement range; and for Gleason score groups kappa ranged from -0.11 to 0.82 with 68.5% of the readings in fair to moderate agreement range. CONCLUSIONS: In our study interobserver reproducibility of Gleason scores among general pathologists was at lower level and it highlights the need to improve the observer reproducibility by continuous educational sessions and taking second opinion in cases where grade could significantly influence management. PMID- 22293267 TI - Periampullary carcinoid: an uncommon tumor at an unusual site. AB - Gastrointestinal carcinoid tumors represent a group of well-differentiated tumors originating from various neuroendocrine cells located in the gastrointestinal mucosa and submucosa. Consequently, there is diversity in their clinical presentation, incidence at specific anatomic sites, biological behavior, hormone production, morphologic characteristics, and immunophenotype. Periampullary carcinoids are extremely rare and less then 100 patients have been reported in the world literature, that too mostly as case reports. We are reporting two cases of periampullary carcinoids, one of which presented with rare manifestation as gastrointestinal bleed and both are doing well after successful pancreatoduodenectomy. PMID- 22293268 TI - Validation of cancer institute quality of life questionnaire version II for cancer patients in India. AB - BACKGROUND: The Quality of Life (QOL) questionnaire version I consisted of 38 items that were validated using 392 patients. The experiences gained through the interaction with the patients during the administration of the questionnaire provided a lot of inputs for the improvization of the tool. AIM: The current study is aimed at certain modifications of the QOL questionnaire version I and standardization of the same. MATERIALS AND METHODS: The modifications of version I QOL scale included the change of verbatim, splitting, deleting, and adding of new items. Finally, version II included 42 items. It was administered to 183 cancer patients irrespective of their demographic details for further standardization. STATISTICS: The principal component method with varimax rotation was used. Spearman's product moment correlation and Cronbach's alpha coefficient were used for reliability analysis. RESULTS: The data were subjected to factor analysis to explore the factors. Eleven factors emerged with the eigenvalue ranging from 8.03 to 1.10 and accounted for 66.7% variance. The first factor contributed maximally, 19.5%, and the remaining 10 factors contributed a total of 46.2% variance on QOL. They are general well-being, physical well-being, psychological well-being, familial relationship, sexual and personal ability, cognitive well-being, optimism and belief, economical well-being, information support, patient-physician relationship, and body image. The Cronbach alpha of 0.90 and split-half reliability of 0.80 indicated a high reliability of the tool. CONCLUSION: The factor structure showed that QOL is a multidimensional concept having different aspects. The Cancer Institute QOL Questionnaire version II for cancer patients is found to be a valid and reliable tool and feasible to administer at the clinical settings. PMID- 22293269 TI - Epigenetic changes in tumor microenvironment. AB - The drama of cancer is not the solo performance of the malignant cells. Microenvironment of the tumor has significant contribution in carcinogenesis. Recent evidences show distinct gene promoter methylation in stromal cells of various malignant and pre-malignant tumors. These changes probably create unique tumor microenvironment, which is responsible for initiation, proliferation, invasion, and metastasis of tumor cells. In this mini review the role of epigenetic changes of tumor microenvironment in carcinogenesis has been discussed. PMID- 22293270 TI - Complimentary role of FDG-PET imaging and skeletal scintigraphy in the evaluation of patients of prostate carcinoma. PMID- 22293271 TI - Which non-small-cell lung cancer patients achieve long-term survival? PMID- 22293272 TI - Primary yolk sac tumor of cervix and vagina in an adult female: a rare case report. PMID- 22293273 TI - A case report: urinoma as initial presenting sign of bladder malignancy. PMID- 22293274 TI - Polymorphous low-grade adenocarcinoma of the palate: report of a case. PMID- 22293275 TI - Psychological disorders in women undergoing postoperative radiation and chemotherapy for breast cancer in India. PMID- 22293276 TI - Low serum sex hormone-binding globulin: marker of inflammation? AB - BACKGROUND: Low sex hormone-binding globulin (SHBG) is associated with metabolic syndrome (MetS), but its relationship with inflammation is unclear. METHODS: This cross-sectional study included 696 subjects (255 men, 235 pre-menopausal women, and 206 postmenopausal women). Body mass index, waist circumference, blood pressure, lipid profiles, plasma glucose, insulin, FSH, LH, total testosterone (TT), estradiol, SHBG, dehydroepiandrosterone sulfate (DHEA-S), and hs-CRP concentrations were measured. MetS was defined according to the updated National Cholesterol Education Program criteria with modification of waist circumference for Asians. RESULTS: Serum hs-CRP and SHBG were negatively correlated in men (r= 0.29, p<0.001), pre-menopausal women (r=-0.38, p<0.001), and postmenopausal women (r=-0.27, p<0.001). In men, TT and hs-CRP showed a negative association (r=-0.25, p<0.001), but the association was attenuated after adjusting for SHBG (r=-0.14, p=0.039). Multivariate regression models showed that SHBG was independently associated with hs-CRP in men (r=-0.18, p=0.009), pre-menopausal women (r=-0.15, p=0.025), and postmenopausal women (r=-0.21, p=0.005), adjusted for age, MetS components, insulin resistance, low-density lipoprotein-cholesterol, and serum sex hormone levels. CONCLUSIONS: Serum SHBG and hs-CRP concentrations were inversely correlated in men, pre-menoposal, and post-menopausal women independently. PMID- 22293277 TI - Inverse correlation between stroke and urinary 3-hydroxypropyl mercapturic acid, an acrolein-glutathione metabolite. AB - BACKGROUND: We found previously that increases in plasma levels of protein conjugated acrolein and polyamine oxidases, enzymes that produce acrolein, are good biomarkers for stroke. The aim of this study was to test whether 3 hydroxypropyl mercapturic acid (3-HPMA), an acrolein-glutathione metabolite, was increased in the urine of stroke patients. METHODS: The level of 3-HPMA in urine was measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Stroke (78 subjects) was divided into 52 cerebral infarction (CI) and 26 cerebral hemorrhage (CH) on the basis of clinical information including brain imaging. RESULTS: A major acrolein derivative in urine is 3-HPMA. Being different from the results of PC-Acro in plasma, 3-HPMA in urine decreased following stroke. The median value of MUmol 3-HPMA/g creatinine (Cre) for 90 control subjects was 2.83, while that for 78 stroke patients was 1.56. The degree of the decrease in 3-HPMA was similar in both CI and CH patients. Furthermore, the median value of MUmol 3 HPMA/g Cre in 56 patients with lesions >= 1cm in diameter (1.39) was significantly lower than that in 20 patients with lesion <1cm in diameter (2.16). CONCLUSION: Inverse correlation between stroke and urinary 3-HPMA was observed. The results suggest that stroke is aggravated when nervous system tissues have a reduced level of glutathione. PMID- 22293278 TI - Survivin gene polymorphism association with papillary thyroid carcinoma. AB - Survivin expression is correlated with suppression of apoptosis in human solid tumors. A polymorphism at position -31 (G/C) (rs 9904341) has been associated with cancer risk in several studies. We evaluated the correlation of this polymorphism with the risk of papillary thyroid carcinoma (PTC) in an Irananian population. The cases consisted of patients with PTC (n=123) and normal controls, composed of non-related healthy people (n=131). The frequency of GC or CC genotype in patients with PTC was significantly higher than in the controls [GC+CC vs GG, p=0.02 OR; 1.7, 95%CI (1.05-3.04)]. There was a significant difference between patients with more aggressive clinical manifestations, including lymphatic involvement compared to the controls [GC+CC vs GG, p=0.0006, OR; 3.7, 95%CI (1.6-9.2)]. The presence of C allele was significantly associated with the presence of more profound manifestations, including lymph node involvement, vascular involvement and multifocality. PMID- 22293279 TI - Association of leptin receptor gene polymorphisms and essential hypertension in a Chinese population. AB - BACKGROUND: The leptin receptor (LEPR) is an important regulator of leptin activity and resistance. Several single nucleotide polymorphisms (SNP) of LEPR have been linked to diseases accompanying obesity and/or obesity-related diseases in different populations. However, the results from published studies remain inconsistent rather than conclusive. AIM: To investigate whether LEPR SNP are associated with essential hypertension and related metabolic traits in Chinese subjects. MATERIALS AND METHODS: A total of 544 Chinese patients with hypertension and 357 non-hypertensive subjects were screened. The genotypes of LEPR polymorphisms were determined by PCR-restriction fragment length polymorphism methods. Demographic and biochemical characteristics including waist circumference, waist-to-hip ratio, body mass index (BMI), lipids profiles, glucose metabolism, and leptin levels were obtained for analysis. RESULTS: This case-control study showed associations between the frequencies of AA genotype and A allele of Gln223Arg and hypertension (p=0.029, p=0.002, respectively). Furthermore, the Gln223Arg polymorphism was significantly associated with plasma leptin levels (p<0.001), while no correlations between Lys109Arg SNP and hypertension were found. Multivariate logistic regression analysis evidenced that A allele carriers of Gln223Arg (AA+AG) showed higher risks of hypertension than GG carriers after adjustment of age and sex (adjusted odds ratio: 1.549, 95% confidence interval: 1.031- 2.036, p=0.035). BMI, fasting serum insulin, oral glucose tolernace test (OGTT)-2h glucose, serum leptin, as well as LDL cholesterol (LDL-C) levels were also independent risk factors of hypertension in this population. In addition, significant associations were observed between the Gln223Arg and Lys109Arg SNP and serum total cholesterol, LDL-C, and fasting plasma glucose levels in hypertensive patients. Besides, A allele of Gln223Arg had raised diastolic blood pressure, compared with GG carriers (p=0.001). While variance of Lys109Arg was associated with waist-to-hip ratio, OGTT-2h glucose, and homeostasis model assessment of insulin resistance (p<0.05). CONCLUSIONS: LEPR polymorphisms may be a marker for susceptibility to essential hypertension in Chinese subjects, and be involved in the development of several features including dyslipidemia and impaired glucose regulation in hypertension subjects. PMID- 22293280 TI - Vertically aligned multiwalled carbon nanotubes for pressure, tactile and vibration sensing. AB - We report a simple method for the micro-nano integration of flexible, vertically aligned multiwalled CNT arrays sandwiched between a top and bottom carbon layer via a porous alumina (Al(2)O(3)) template approach. The electromechanical properties of the flexible CNT arrays have been investigated under mechanical stress conditions. First experiments show highly sensitive piezoresistive sensors with a resistance decrease of up to ~35% and a spatial resolution of <1 mm. The results indicate that these CNT structures can be utilized for tactile sensing components. They also confirm the feasibility of accessing and utilizing nanoscopic CNT bundles via lithographic processing. The method involves room temperature processing steps and standard microfabrication techniques. PMID- 22293281 TI - Dietary strawberry powder reduces blood glucose concentrations in obese and lean C57BL/6 mice, and selectively lowers plasma C-reactive protein in lean mice. AB - The purpose of the present study was to test the anti-inflammatory and blood glucose (BG)-regulating capacity of strawberries in a mouse model of diet-induced obesity. A total of thirty-six male C57BL/6J mice were randomly divided into four groups (nine mice per group). Mice were fed a low-fat diet (LF, 13 % fat), the LF supplemented with 2.6 % freeze-dried strawberry powder (LFSB), a high-fat diet (HF, 44 % fat) or the HF supplemented with 2.6 % strawberry powder (HFSB). Blood samples were collected to measure BG, inflammation and systemic markers for endocrine function of pancreas and adipose tissue. Splenocytes were harvested at the end of the study and activated with either anti-cluster of differentiation (CD) 3/anti-CD28 antibodies or lipopolysaccharide to test immune responsiveness. The HF increased non-fasted BG, insulin, soluble intracellular adhesion molecule 1, E-selectin, leptin, resistin and plasminogen activator protein-1 (P < 0.05). High dietary fat decreased IL-4 production from activated splenocytes (P < 0.05). BG concentrations were lower in the mice supplemented with SB (10.64 mmol/l) compared to the non-supplemented mice (11.37 mmol/l; P = 0.0022). BG values were approximately 6.5 % lower in the supplemented mice. Additionally, SB lowered plasma C-reactive protein in the LFSB group compared to the other three groups (P < 0.05). The dietary intake of SB approximated one human serving of strawberries. These results, although modest, support a promising role for dietary strawberries in reducing the risks associated with obesity and diabetes, and regulating the levels of inflammatory markers in non-obese individuals. PMID- 22293282 TI - Kinetics and tissue distribution of neutron-activated zinc oxide nanoparticles and zinc nitrate in mice: effects of size and particulate nature. AB - Although zinc oxide nanoparticles (ZnONPs) have been applied in nanotechnology, their kinetics and tissue distribution in vivo are unknown. Here we compared the kinetics and tissue distribution of 10 nm (65)ZnONPs, 71 nm (65)ZnONPs and (65)Zn(NO(3))(2) in mice after intravenous injection. The areas under the curves and the half-lives in the second compartment of (65)Zn(NO(3))(2) were greater than those of (65)ZnONPs; the kinetic parameters were similar for both (65)ZnONPs. However, the tissue distributions for the three forms were different. ZnONPs preferentially accumulated in the liver and spleen at 24 h. At day 28, (65)Zn concentration was highest in bone and the proportion of recovered (65)Zn radioactivity was highest in the carcass; these had the same ranking, 10 nm (65)ZnONPs > 71 nm (65)ZnONPs> (65)Zn(NO(3))(2). Although more than 80% of the 10 nm (65)ZnONPs had been excreted by day 28, greater amounts of the 10 nm (65)ZnONPs than the 71 nm (65)ZnONPs or (65)Zn(NO(3))(2) had accumulated in other organs (brain, lung, heart and kidneys). Zn ions seem to have a longer half-life in the plasma, but ZnONPs show greater tissue accumulation. Although the size of the ZnONPs had no obvious effect on the kinetics, nevertheless the smaller ZnONPs tended to accumulate preferentially in some organs. PMID- 22293283 TI - Rapid identification of ophiopogonins and ophiopogonones in Ophiopogon japonicus extract with a practical technique of mass defect filtering based on high resolution mass spectrometry. AB - This study was to develop and evaluate a practical approach of mass defect filtering (MDF), a post-acquisition data processing technique, for the rapid classification of complicated peaks into well-known chemical families based on the exact mass acquired by high resolution mass spectrometry. The full-scan LC MS/MS data of the Ophiopogon japonicus extract was acquired using high performance liquid chromatography coupled with hybrid quadrupole-time of flight (LCMS-Q-TOF) system which features high resolution, mass accuracy, and sensitivity. To remove the interferences of the complex matrix, MDF approach was developed and employed to rapidly pick out the peaks of ophiopogonins and ophiopogonones from full-scan mass chromatograms. The accuracy of MDF was evaluated in reference to the result of structural identification. After the MDF based classification, both target and non-target components in Ophiopogon japonicus extract were characterized based on the detailed fragment ions analysis in the hybrid ion trap and time-of-flight mass spectrometry (LCMS-IT-TOF). By this approach, more than 50 ophiopogonins and 27 ophiopogonones were structurally characterized. The present results of rapid detection and identification of ophiopogonins and ophiopogonones suggest that the proposed MDF approach based on the high-resolution mass spectrometry data would be expected adaptable to the analysis of other herbal components. PMID- 22293284 TI - Fractionation of polyethylene glycol particles by simulated moving bed with size exclusion chromatography. AB - In this study, a three-section simulated moving bed (SMB) with an open-loop design is used to fractionate polyethylene glycol (PEG) with different molecular weights. The purchased PEGs are mixed and separated by the open-loop SMB. A size exclusion column with a pore size ranging from 10 to 100 nm, TOSOH GMPW 7.5 mm * 30 cm, is used to separate the mixtures. Based on the Triangle theory, the operating parameters of the SMB are determined and used to separate the three binary mixtures. The results show that the PEG mixtures with molecular weights of 400 and 8000, and those of 1500 and 20,000, are separable, yet those of 1500 and 3500 are difficult to separate by the selected column. The relative elution for molecular weights of 400 and 8000, and 1500 and 2000, is 1.49 and 1.54, respectively, resulting in easy separation. However, the difference in the elution volume for mixtures with molecular weights of 1500 and 3500 is so small that the operation condition is confined to a tiny area on the (m(2), m(3)) plane defined by the Triangle theory. This makes robust application of the SMB impossible. Fortunately, it is still possible to obtain pure raffinate with low recovery, but a pure extract is still not possible. It is concluded that the low selectivity of the binary mixture and the fluctuation of the operation result in the difficulty in separating the 1500 and 3000 molecular weight mixtures. This paper presents the operation procedures, including the selection of the column, the discovery of selectivity, the application of the Triangle theory and the experimental results, in order to illustrate how to apply an SMB to the fractionation of PEGs. PMID- 22293285 TI - Levels and congener profiles of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) in sheep milk from an industrialised area of Sardinia, Italy. AB - Concentrations of 7 polychlorinated dibenzo-p-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs) and 22 polychlorinated biphenyls (PCBs), including 12 dioxin like-PCBs (non- and mono-ortho PCBs) were measured in 80 sheep milk samples from farms located in an industrialized area of Sardinia, Italy. PCDDs and PCDFs mean concentrations were 2.45 and 3.69 pgg(-1) fat basis, respectively. The mean dl-PCB concentration was 2.01 ngg(-1) fat basis, while cumulative ndl PCB levels ranged from 1.02 to 20.42, with a mean of 4.92 ngg(-1) fat. The results expressed in pg WHO-TEQ/g fat showed that contamination level of milk was below the limit values for human consumption established by EC legislation. In the same way, all the investigated milk exhibited PCDD/Fs concentrations below EU action levels, while dl-PCBs concentrations exceeded the action level of 2.0 pg WHO-TEQ/g fat. These findings point to the need to continue to conduct general monitoring programmes, including also milk samples from areas not close to the contaminant-emitting industries, in order to better evaluate the impact of industrial activities on surrounding environment. PMID- 22293286 TI - A profile of immune response to herpesvirus is associated with radiographic joint damage in rheumatoid arthritis. AB - INTRODUCTION: Progression of joint damage despite appropriate therapy remains a significant problem for patients with rheumatoid arthritis (RA). This study was undertaken to identify profiles of immune response that correlate with radiographic joint damage as a first step toward the discovery of new pathogenic mechanisms of joint destruction in RA. METHODS: The study included 58 patients with RA and 15 healthy controls. The profiles of cytokine release from peripheral blood mononuclear cells (PBMC) in response to stimulation for 48 hours with one of six stimuli, or in media alone, were measured. Immune response profiles identified for each stimulus were correlated with radiographic joint damage as defined by the Sharp-van der Heijde score (SHS), before and after multivariable adjustment. For profiles correlated with the SHS, the distributions of individual cytokines were evaluated in patients according to the severity of joint damage and compared to healthy controls. RESULTS: The immune response profile for cytomegalovirus (CMV)/Epstein-Barr virus (EBV) stimulation was correlated with both the SHS total and erosion scores (r = 0.31, P = 0.018 and r = 0.33, P = 0.011, respectively). After adjusting for age, sex, disease duration, autoantibody status, CMV/EBV serological status, current disease activity, disability and treatments, the correlation of the CMV/EBV immune response and the SHS erosion score became stronger (r = 0.43, P < 0.003). The CMV/EBV immune response correlated with CMV IgG (r = 0.44, P < 0.001), but not with EBV IgG. The most important cytokines for the CMV/EBV immune response profile were IFN-gamma, IL-2, IL-4, IL-5, IL-13 and IL-17A, all of which are associated with T-cell immunity. Both the summary immune response score and the individual responses of IFN-gamma and IL-13 to CMV/EBV stimulation were associated with greater joint damage. CONCLUSIONS: A profile of immune response to purified CMV/EBV lysates is associated with radiographic joint damage. The correlation of this immune response to CMV serology implies possible involvement of latent CMV infection. Therefore, the findings suggest that the immune response to latent CMV infection could play a fundamental role in the progression of inflammation and structural joint damage in patients with RA. PMID- 22293287 TI - Involvement of Plasmodium falciparum protein kinase CK2 in the chromatin assembly pathway. AB - BACKGROUND: Protein kinase CK2 is a pleiotropic serine/threonine protein kinase with hundreds of reported substrates, and plays an important role in a number of cellular processes. The cellular functions of Plasmodium falciparum CK2 (PfCK2) are unknown. The parasite's genome encodes one catalytic subunit, PfCK2alpha, which we have previously shown to be essential for completion of the asexual erythrocytic cycle, and two putative regulatory subunits, PfCK2beta1 and PfCK2beta2. RESULTS: We now show that the genes encoding both regulatory PfCK2 subunits (PfCK2beta1 and PfCK2beta2) cannot be disrupted. Using immunofluorescence and electron microscopy, we examined the intra-erythrocytic stages of transgenic parasite lines expressing hemagglutinin (HA)-tagged catalytic and regulatory subunits (HA-CK2alpha, HA-PfCK2beta1 or HA-PfCK2beta2), and localized all three subunits to both cytoplasmic and nuclear compartments of the parasite. The same transgenic parasite lines were used to purify PfCK2beta1- and PfCK2beta2-containing complexes, which were analyzed by mass spectrometry. The recovered proteins were unevenly distributed between various pathways, with a large proportion of components of the chromatin assembly pathway being present in both PfCK2beta1 and PfCK2beta2 precipitates, implicating PfCK2 in chromatin dynamics. We also found that chromatin-related substrates such as nucleosome assembly proteins (Naps), histones, and two members of the Alba family are phosphorylated by PfCK2alpha in vitro. CONCLUSIONS: Our reverse-genetics data show that each of the two regulatory PfCK2 subunits is required for completion of the asexual erythrocytic cycle. Our interactome study points to an implication of PfCK2 in many cellular pathways, with chromatin dynamics being identified as a major process regulated by PfCK2. This study paves the way for a kinome-wide interactomics-based approach to elucidate protein kinase function in malaria parasites. PMID- 22293288 TI - Norkurarinol inhibits toll-like receptor 3 (TLR3)-mediated pro-inflammatory signaling pathway and rotavirus replication. AB - This study examined the effect of norkurarinol on the toll-like receptor 3 (TLR3) mediated signaling pathways and rotavirus replication. Norkurarinol, a lavandulylated flavanone, was isolated from the roots of Sophora flavescens, which has been shown to have anti-inflammatory activity. Norkurarinol suppressed the NF-kappaB and AP-1 inducible secreted embryonic alkaline phosphatase (SEAP) activity induced by poly(I:C), TLR3 ligand, in THP1-Blue-CD14 cells with IC(50) values of 20.9 uM. Norkurarinol also significantly suppressed the mRNA expression of pro-inflammatory and adhesive molecules induced by poly(I:C) and rotavirus infection. Pretreatment of norkurarinol blocked the NF-kappaB and AP-1 signaling pathway and the phosphorylation of MAPKs induced by poly(I:C). On the other hand, norkurarinol increased the level of IRF3 phosphorylation and IFNbeta expression in a dose-dependent manner. Moreover, norkurarinol inhibited the rotavirus induced cytopathic effects. These results suggest that norkurarinol can modulate the TLR3-mediated inflammatory responses and rotavirus replication. PMID- 22293289 TI - Insulin induces internalization of the plasma membrane 5-hydroxytryptamine2A (5 HT2A) receptor in the isolated human endothelium-denuded saphenous vein via the phosphatidylinositol 3-kinase pathway. AB - The aim of this study was to investigate the relaxant effect of insulin on the 5 hydroxytryptamine (5-HT)-induced constriction of the human endothelium-denuded saphenous vein (SV) and its signal transduction pathway. During the 5-HT-induced sustained constriction of vessels, insulin induced vasorelaxation in a concentration-dependent manner. This insulin-induced vasorelaxation was partially attenuated by L-NAME, a nitric oxide synthase (NOS) inhibitor, and was abolished by wortmannin, a phosphatidylinositol 3-kinase (PI3-K) inhibitor. Insulin increased the Ser(473) phosphorylation of Akt. Endothelial NOS and inducible NOS protein expressions were observed in SV smooth muscle when insulin induced relaxation of SV vessels preconstricted with 5-HT. Although insulin did not affect the total protein level of 5-HT(2A) receptors, it decreased the particulate protein level and reciprocally increased the soluble protein level of 5-HT(2A) receptors in a concentration-dependent manner. These results demonstrate that insulin can induce the internalization of 5-HT(2A) receptors from the plasma membrane to the cytoplasm. The insulin-induced internalization of 5-HT(2A) receptors was abolished by wortmannin but was not affected by L-NAME. These results suggest that the relaxant effect of insulin on 5-HT-induced vasoconstriction is mediated in part by the internalization of plasma membrane 5 HT(2A) receptors and the production of nitric oxide via the PI3-K/Akt pathway. PMID- 22293290 TI - The selective metabotropic glutamate 2/3 receptor agonist MGS0028 reverses isolation rearing-induced abnormal behaviors in mice. AB - Isolation-induced abnormal behaviors are useful animal models for assessing potential anti-psychotic drugs. This study examined the effect of MGS0028, a selective metabotropic glutamate 2/3 receptor agonist, on abnormal behaviors such as hyperactivity, aggression, and deficits of prepulse inhibition in isolation reared mice. MGS0028 attenuated hyperactivity and aggressive behaviors in isolation-reared mice. The agonist also reversed isolation rearing-induced deficits of prepulse inhibition. On the other hand, MGS0028 did not affect locomotor activity and prepulse inhibition in group-reared mice. These results suggest that the metabotropic glutamate 2/3 receptor agonist, MGS0028, is a potential compound for the treatment of psychiatric disorders. PMID- 22293291 TI - New therapeutic strategy for amino acid medicine: prophylactic and healing promoting effect of monosodium glutamate against NSAID-induced enteropathy. AB - We reviewed the effect of monosodium glutamate (MSG) on the development and healing of nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal lesions in rats. Loxoprofen (60 mg/kg, p.o.) induced lesions in the small intestine within 24 h, accompanied by a decrease of Muc2 expression and an increase in enterobacterial invasion and inducible nitric oxide synthase (iNOS) expression. These lesions were prevented when MSG was given as a mixture of powdered food for 5 days before the loxoprofen treatment. This effect of MSG was accompanied by an increase in Muc2 expression / mucus secretion as well as the suppression of bacterial invasion and iNOS expression. These intestinal lesions healed spontaneously within 6 days, but the process was impaired by the repeated administration of low-dose loxoprofen (30 mg/kg) for 5 days after the ulceration, with the decrease of vascular endothelial derived growth factor (VEGF) expression and angiogenesis. The healing-impairing effect of loxoprofen was prevented by feeding 5% MSG for 5 days after the ulceration. These results suggest that MSG not only prevents loxoprofen-induced small intestinal damage but also promotes a healing of these lesions; the former is functionally associated with the increase in Muc2 expression / mucus secretion and the suppression of bacterial invasion and iNOS expression, while the latter is associated with the stimulation of VEGF expression/angiogenesis. PMID- 22293292 TI - New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. AB - Glycine is a non-essential amino acid that has indispensable roles in both excitatory and inhibitory neurotransmission via N-methyl-D-aspartate type glutamate receptors and glycine receptors, respectively. We recently reported that glycine ingestion before bedtime significantly ameliorated subjective sleep quality in individuals with insomniac tendencies. Oral administration of glycine to rats was found to induce a significant increase in the plasma and cerebrospinal fluid glycine concentrations and a significant decrease in the core body temperature associated with an increase in cutaneous blood flow. The decline in the core body temperature might be a mechanism underlying glycine's effect on sleep, as the onset of sleep is known to involve a decrease in the core body temperature. Moreover, a low core body temperature is maintained during sleep in humans. Pharmacological studies investigating the mechanisms of glycine on sleep were also performed. In this review, we will describe both our recent findings regarding how and where orally administered glycine acts and findings from our rat study and human trials. PMID- 22293293 TI - New therapeutic strategy for amino acid medicine: notable functions of branched chain amino acids as biological regulators. AB - The branched chain amino acids (BCAAs) leucine, isoleucine, and valine are the most abundant of the essential amino acids. BCAAs have recently been recognized as having functions other than simple nutrition. The importance of BCAAs as nutrient regulators in protein synthesis was recognized over 20 years ago. Leucine is the most potent of the BCAAs in stimulating muscle protein synthesis, while isoleucine and valine are much less effective. The signaling action of leucine in protein synthesis has been well studied, and the mechanisms are currently under investigation. However, the pharmacological effects of isoleucine and valine have not been clarified. It has recently been reported that, among the BCAAs, leucine and isoleucine act as signals in glucose metabolism. We revealed that isoleucine stimulates both glucose uptake in the muscle and whole body glucose oxidation, in addition to depressing gluconeogenesis in the liver, thereby leading to a hypoglycemic effect in rats. Based on these results, we speculate that isoleucine signaling accelerates catabolism of incorporated glucose for energy production and consumption. PMID- 22293294 TI - New therapeutic strategy for amino acid medicine: effects of dietary glutamate on gut and brain function. AB - The gustatory and visceral stimulation from food regulates digestion and nutrient utilization, and free glutamate (Glu) release from food is responsible for the umami taste perception that increases food palatability. The results of recent studies reveal a variety of physiological roles for Glu. For example, luminal applications of Glu into the mouth, stomach, and intestine increase the afferent nerve activities of the glossopharyngeal nerve, the gastric branch of the vagus nerve, and the celiac branch of the vagus nerve, respectively. Additionally, luminal Glu evokes efferent nerve activation of each branch of the abdominal vagus nerve. The intragastric administration of Glu activates several brain areas (e.g., insular cortex, limbic system, and hypothalamus) and has been shown to induce flavor-preference learning in rats. Functional magnetic resonance imaging of rats has shown that the intragastric administration of Glu activates the nucleus tractus solitarius, amygdala, and lateral hypothalamus. In addition, Glu may increase flavor preference as a result of its postingestive effect. Considering these results, we propose that dietary Glu functions as a signal for the regulation of the gastrointestinal tract via the gut-brain axis and contributes to the maintenance of a healthy life. PMID- 22293295 TI - New therapeutic strategy for amino acid medicine: preface. PMID- 22293296 TI - Sense of taste in the gastrointestinal tract. AB - Recent advances in molecular biology have led to the investigation of the molecular mechanism by which chemicals such as odors and tastants are perceived by specific chemosensory organs. For example, G protein-coupled receptors expressed within the nasal epithelium and taste receptors in the oral cavity have been identified as odorant and taste receptors, respectively. However, there is much evidence to indicate that these chemosensory receptors are not restricted to primary chemosensory cells; they are also expressed and have function in other cells such as those in the airways and gastrointestinal (GI) tract. This short review describes the possible mechanisms by which taste signal transduction occurs in the oral cavity and tastants/nutrients are sensed in the GI tract by taste-like cells, mainly enteroendocrine and brush cells. Furthermore, it discusses the future perspectives of chemosensory studies. PMID- 22293297 TI - Hypoxic stress induces transient receptor potential melastatin 2 (TRPM2) channel expression in adult rat cardiac fibroblasts. AB - When cardiac tissue is exposed to hypoxia, myocytes are damaged, while fibroblasts are activated. However, it is unknown what changes are induced by hypoxia in cardiac fibroblasts. In this study, using the whole cell patch-clamp technique, we investigated the effect of hypoxia on membrane currents in fibroblasts primarily cultured from adult rat hearts. Cardiac fibroblasts were incubated for 24 h under normoxic or hypoxic conditions using Anaeropack. Hypoxia increased a current which reversed at around -20 mV in the cardiac fibroblasts. This current was inhibited by clotrimazole, which is an inhibitor of transient receptor potential melastatin 2 (TRPM2) channel and intermediate-conductance Ca(2+)-activated K(+) channel (KCa3.1). ADP ribose in the pipette solution enhanced this current. Quantitative RT-PCR revealed that mRNA of TRPM2, but not that of KCa3.1, was increased by hypoxia. RNA interference of TRPM2 prevented the development of the hypoxia-induced current. H(2)O(2), an activator of TRPM2 channel, induced a higher [Ca(2+)](i) elevation in hypoxia-exposed cardiac fibroblasts than that in normoxia-exposed cells. We conclude that hypoxia induces TRPM2 channel expression in adult rat cardiac fibroblasts. PMID- 22293298 TI - The cadin-2-en-1beta-ol-1beta-D-glucuronopyranoside suppresses TPA-mediated matrix metalloproteinase-9 expression through the ERK signaling pathway in MCF-7 human breast adenocarcinoma cells. AB - A sesquiterpene glycoside, cadin-2-en-1beta-ol-1beta-D-glucuronopyranoside (known as CR4-1), was isolated from Catharanthus roseus (Apocynaceae) hairy root cultures. C. roseus is widely used as an ornamental and medicinal plant and is cultivated mainly for its alkaloids. C. roseus has been reported to have pharmacologic properties such as anti-cancer, enzymatic anti-oxidant, and anti diabetic effects. In this study, we demonstrated that CR4-1 significantly inhibited the in vitro invasion of MCF-7 human breast adenocarcinoma cells induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA). Matrix metalloproteinases (MMPs) are known to be involved in cancer invasion and metastasis. Zymographic analysis showed that CR4-1 suppressed TPA-induced MMP-9 activity in a dose dependent manner. We further demonstrated that CR4-1 suppressed the phosphorylation of extracellular signal-regulated protein kinase, but not p38 kinase or c-Jun N-terminal kinase (JNK). Moreover, CR4-1 attenuated TPA-induced degradation of kappaBalpha inhibitor (IkappaB-alpha). These results suggest that CR4-1 reduces the invasiveness of human cancer cells by suppressing MMP-9 expression through inhibition of the NF-kappaB signaling pathways. PMID- 22293299 TI - Cannabinoid receptor activation disrupts the internal structure of hippocampal sharp wave-ripple complexes. AB - Cannabinoid agonists impair hippocampus-dependent learning and memory. Using mouse hippocampal slice preparations, we examined the effect of anandamide, an endogenous cannabinoid, on sharp wave-ripple (SW-R) complexes, which are believed to mediate memory consolidation during slow-wave sleep or behavioral immobility. Anandamide reduced the frequency of SW-Rs recorded from the CA3 region, and this effect was abolished by AM251, a cannabinoid CB1-receptor antagonist. We further addressed the action of anandamide using a functional multineuron calcium imaging technique. Anandamide reduced the firing rate of hippocampal neurons as well as disrupted the temporal coordination of their firings during SW-R. PMID- 22293300 TI - Effect of aripiprazole on anxiety associated with ethanol physical dependence and on ethanol-induced place preference. AB - In the present study, we investigated the effect of aripiprazole, a dopamine system stabilizer, on ethanol-induced psychological and physiological dependence and anxiety-like behavior. First we determined the effect of aripiprazole, a dopamine system stabilizer, on the development and expression of ethanol-induced place preference. Both the development and expression of ethanol-induced place preference was significantly suppressed by treatment of aripiprazole. Next, the withdrawal score gradually increased with increasing duration after the withdrawal from ethanol for 6 days in vehicle-treated mice and the maximal score was observed 10 h after the ethanol withdrawal. Aripiprazole caused no changes in the withdrawal score as compared to vehicle-treated mice. Under these conditions we investigated the effect of aripiprazole on the anxiety-like behavior of ethanol physical dependent mice, which were animals subjected to ethanol vapor for 6 days. The significant decrease of time spent in the open arms and number of open arm entries characterize the anxiety-like behavior in ethanol physical dependent mice, compared to control mice. These decreases were reversed by treatment of aripiprazole, which were inhibited by WAY100635, a serotonin 5 HT(1A) receptor antagonist. The present findings suggest that aripiprazole was efficient for reversing ethanol-induced place preference and anxiety-like behavior. PMID- 22293301 TI - Direct effects of esmolol and landiolol on cardiac function, coronary vasoactivity, and ventricular electrophysiology in guinea-pig hearts. AB - The ultra-short acting, selective beta(1)-adrenergic antagonists landiolol and esmolol are widely used perioperatively; however, little is known about their acute direct actions on the heart. The current study utilized the Langendorff perfused heart system to measure changes in cardiac function and hemodynamics in response to each drug. Furthermore, electrophysiological analysis was performed on isolated ventricular myocytes. Direct application of esmolol significantly decreased systolic left ventricular pressure and heart rate at concentrations > 10 uM, while it dose-dependently increased coronary perfusion pressure. Esmolol also shortened the action potential duration (APD) in a concentration-dependent manner, an action maintained even when the delayed rectifier K(+) current or ATP sensitive K(+) current was blocked. Moreover, esmolol inhibited both the inward rectifier K(+) current (I(K1)) and the L-type Ca(2+) current (I(CaL)) and increased the outward current dose-dependently. In contrast, landiolol had minimal cardiac effects. In the Kyoto Model computer simulation, inhibition of either I(K1) or I(CaL) alone failed to shorten the APD; however, an additional increase in the time-independent outward current caused shortening of the APD, equal to that induced by esmolol. In conclusion, esmolol directly inhibits cardiac performance significantly more so than landiolol, an effect revealed to be at least in part mediated by esmolol-induced APD shortening. PMID- 22293302 TI - New approaches to prophylactic human papillomavirus vaccines for cervical cancer prevention. AB - The currently licensed human papillomavirus (HPV) vaccines are safe and highly effective at preventing HPV infection for a select number of papillomavirus types, thus decreasing the incidence of precursors to cervical cancer. It is expected that vaccination will also ultimately reduce the incidence of this cancer. The licensed HPV vaccines are, however, type restricted and expensive, and also require refrigeration, multiple doses and intramuscular injection. Second-generation vaccines are currently being developed to address these shortcomings. New expression systems, viral and bacterial vectors for HPV L1 capsid protein delivery, and use of the HPV L2 capsid protein will hopefully aid in decreasing cost and increasing ease of use and breadth of protection. These second-generation vaccines could also allow affordable immunization of women in developing countries, where the incidence of cervical cancer is high. PMID- 22293303 TI - Phylogenetic, genomic organization and expression analysis of hydrophobin genes in the ectomycorrhizal basidiomycete Laccaria bicolor. AB - Hydrophobins are morphogenetic, small secreted hydrophobic fungal proteins produced in response to changing development and environmental conditions. These proteins are important in the interaction between certain fungi and their hosts. In mutualistic ectomycorrhizal fungi several hydrophobins form a subclass of mycorrhizal-induced small secreted proteins that are likely to be critical in the formation of the symbiotic interface with host root cells. In this study, two genomes of the ectomycorrhizal basidiomycete Laccaria bicolor strains S238N-H82 (from North America) and 81306 (from Europe) were surveyed to construct a comprehensive genome-wide inventory of hydrophobins and to explore their characteristics and roles during host colonization. The S238N-H82 L. bicolor hydrophobin gene family is composed of 12 genes while the 81306 strain encodes nine hydrophobins, all corresponding to class I hydrophobins. The three extra hydrophobin genes encoded by the S238N-H82 genome likely arose via gene duplication and are bordered by transposon rich regions. Expression profiles of the hydrophobin genes of L. bicolor varied greatly depending on life stage (e.g. free living mycelium vs. root colonization) and on the host root environment. We conclude from this study that the complex diversity and range of expression profiles of the Laccaria hydrophobin multi-gene family have likely been a selective advantage for this mutualist in colonizing a wide range of host plants. PMID- 22293304 TI - Emergency medicine in the Netherlands: a short history provides a solid basis for future challenges. PMID- 22293305 TI - Left atrial myxoma complicated with an acute upper extremity embolism. AB - Atrial myxoma is the most common benign tumor of the heart. Patients who have atrial myxoma usually present with cardiac obstruction, arrhythmia, or peripheral embolization. We encountered an unusual case of acute upper extremity ischemia due to a massive atrial myxoma in a young man. A 38-year-old man was admitted to our hospital with an acute onset of severe, right upper extremity pain and paralysis while working. Neurologic examination yielded normal results, but the patient showed no palpable right radial or ulnar artery. Routine sonographic evaluation revealed acute aortic embolism in his right brachial artery. Because of his young age and otherwise healthy condition, we decided to perform transthoracic echocardiography, which showed a huge left atrial tumor, which we suspected to be myxoma. We then performed urgent concurrent open heart surgery and embolectomy to avoid further embolism. The microscopic findings of the resected tumor and embolism specimens were myxoma. He was discharged without complications. PMID- 22293306 TI - Multiple cardiac perforations following radiofrequency catheter ablation: case report and literature reviews. AB - INTRODUCTION: Multiple cardiac ruptures after radiofrequency catheter ablation that requires surgical repair are uncommon. METHODS AND RESULTS: We describe a 64 year old male patient with paroxysmal atrial fibrillation who had a cardiac tamponade following radiofrequency ablation. Surgical exploration demonstrated two ruptures in the left atrium, one in the right atrium, and one hematoma in the right atrium. MEDLINE, the Cochrane Library, and related databases were searched up to June 2011 without language restrictions, and related literature was reviewed and discussed. The patient has survived from prompt cardiac repair of cardiac ruptures and recovered from surgery without complications. CONCLUSIONS: Urgent exploratory surgery with cardiopulmonary bypass is the key to salvage the patient. PMID- 22293307 TI - Miliary tuberculosis complicated by pulmonary cavitations and pneumothorax in a 14-month old boy. AB - Surgical management of tuberculosis is uncommon in children. We report a case of a 14-month-old boy with miliary tuberculosis and recurrent pneumothorax due to cavities in the left lung. This boy had no previous medical history and was referred to our hospital for a severe pneumonia. Initial chest radiograph showed bilateral miliary pattern. Direct microscopy of gastric lavage showed the presence of tubercle bacilli, providing definitive diagnosis. In spite of effective medication, his status rapidly worsened. A cardiac resuscitation was followed by intubation, and he required high-pressure ventilation for four weeks. He developed left pneumothorax, for which several drainages were performed. Computed tomography revealed a huge cavern system involving the entire lingula and surrounded by the left pneumothorax. Eventually, a massive enlargement of the initial cavity necessitated a thoracotomy and wedge resection. PMID- 22293308 TI - Dissecting aneurysm in a patient with autosomal dominant polycystic kidney disease. AB - Autosomal dominant polycystic kidney disease (ADPKD) is primarily associated with renal failure, but it also causes systemic diseases, including cysts of other systemic organs and cerebral or visceral aneurysm. To make matters worse, life threatening aortic diseases are associated with ADPKD in some cases. However, only a few reports of ADPKD-associated with thoracic aortic dissection have been published. Herein, we present a case of dissecting aneurysm in a patient with hypertension and ADPKD. He had been followed up for type B aortic dissection for six years. Preoperative creatinine level ranged from 2.1 to 2.4 mg/dl. We performed replacement of the thoracic aorta with prosthetic graft successfully, and postoperatively, dialysis was not required.It is very important for us to recognize the relationship between ADPKD and thoracic aortic dissection, which can cause high mortality and morbidity rates. PMID- 22293310 TI - Atypically located pericardial cyst in a patient who underwent off-pump myocardial revascularization. AB - Pericardial cysts are rare benign mediastinal lesions and most commonly located at the cardiophrenic angle. We present a case of an atypically located pericardial cyst in a patient who underwent myocardial revascularization. A 61 year-old man with acute myocardial infarction was scheduled for coronary artery bypass grafting (CABG). Preoperative chest computed tomography revealed a homogenous cystic lesion in the superior mediastinum. The mass was located between the ascending aorta, the superior vena cava, and the left innominate vein. It was growing to the anterior of the aorta and to the right anterior paratracheal area. The density of the mass was close to that of water; thus, the contrast medium failed to enhance its visualization. A concomitant resection of the mass and the CABG was scheduled. After a medial sternotomy and bypass graft harvest, a median pericardectomy was performed. The surgeon found the cystic mass along the roof of the pericardium and located between the ascending aorta and superior vena cava. There was no adhesion between the mass and cardiovascular components. The mass was resected en bloc; therefore, off-pump CABG was completed. Histopathological examination of the resected specimen confirmed diagnosis of a pericardial cyst. PMID- 22293311 TI - A congenital arteriovenous malformation originating from the aorta locating in the posterior mediastinum. AB - Vascular malformations located in the posterior mediastinum are extremely rare. Most of them are found coincidentally during routine examinations. Only a small percentage of these posterior mediastinal arteriovenous malformation cases may cause symptoms such as dyspnea due to compression of surrounding tissues. Radiologic imaging can be insufficient in some cases for differential diagnosis. Because of their vascular nature, diagnostic needle biopsy may have a high risk of bleeding. Open surgical resection is a safe treatment choice under many circumstances, and it helps the diagnosis as well. In this paper, a case of a 31 year-old male is presented with an incidentally diagnosed arteriovenous malformation, originating from the descending aorta and located in the posterior mediastinum. PMID- 22293312 TI - Thoratec HeartMate II((r)) left ventricular assist device implantation in patient with patent ventriculoperitoneal shunt. AB - We report a case of HeartMate II((r)) left ventricular assist device (LVAD) implantation as a destination therapy in a patient with a patent ventriculoperitoneal (VP) shunt after being suffered from subarachnoid hemorrhage. Because the patient's VP shunt was running through her right anterior chest and abdominal wall, a driveline exit site was selected in her left upper quadrant to avoid unnecessary perioperative complication in relation to the patent VP shunt tube. Tailored driveline placement was a key element of this LVAD implantation in this already sick patient with multiple comorbidities. PMID- 22293314 TI - Aortic annulus diameter measurement: what is the best modality? AB - PURPOSE: The purpose of this study was to clarify the most suitable method to measure the aortic annulus diameter. PATIENTS AND METHODS: Fifty-five patients, who had undergone aortic valve replacement at Miyazaki University Hospital between April 2008 and May 2011, were included in this study. The maximum diameter of the sizing tool that could be inserted into the left ventricle through the annulus had been predicted, based on the diameter measured by each modality. Agreement with surgery and each imaging modality, namely transthoracic echocardiography, multidetector computed tomography and contrast angiography, were compared using Bland-Altman analysis. RESULTS: The predicted aortic annulus diameter, based on the diameter measured by transthoracic echocardiography, multidetector computed tomography and contrast angiography, was 20.3 +/- 2.50, 23.9 +/- 3.19, and 23.5 +/- 3.55 mm, respectively, whereas, the diameter measured at surgery was 23.7 +/- 2.99 mm. Predicted aortic annulus diameter measured by multidetector computed tomography best agreed with that measured at surgery. CONCLUSION: We conclude that the aortic annulus diameter, measured by multidetector computed tomography, is the best modality to measure the aortic annulus diameter. PMID- 22293315 TI - Direct-write fabrication of freestanding nanocomposite strain sensors. AB - This paper deals with the design and microfabrication of two three-dimensional (3D) freestanding patterned strain sensors made of single-walled carbon nanotube (SWCNT) nanocomposites with the ultraviolet-assisted direct-write (UV-DW) technique. The first sensor consisted of three nanocomposite microfibers suspended between two rectangular epoxy pads. The flexibility of the UV-DW technique enables the sensor and its housing to be manufactured in one monolithic structure. The second sensor was composed of a nanocomposite network consisting of four parallel microsprings, which demonstrates the high capability of the technique when compared to conventional photolithographic technologies. The performances of the sensors were assessed under tension and compression, respectively. The sensors' sensitivities were evaluated by correlating their measured resistivities to the applied displacements/strains. Electrical conductivity measurements revealed that the manufactured sensors are highly sensitive to small mechanical disturbances, especially for lower nanotube loadings when compared to traditional metallic or nanocomposite films. The present manufacturing method offers a new perspective for manufacturing highly sensitive 3D freestanding microstructured sensors. PMID- 22293316 TI - Laboratory values in a Spanish population of older adults: a comparison with reference values from younger adults. AB - OBJECTIVE: To examine the laboratory indices in a population aged 65 years or more and compare them with the reference values used for young adults. STUDY DESIGN: Distribution patterns of frequently used biochemical and hematological indices were examined in a sample (N=600) of non-institutionalized adults aged over 65. OUTCOME MEASURES: The obtained values were compared with the reference intervals for young adults. RESULTS: On some of the indices analyzed, large proportions of the participants had values above the upper limit of the reference interval: glucose, 25.0%; urea, 26.6%; creatinine, 27.2% of males; total cholesterol, 54.6%; and low-density lipoprotein cholesterol, 35.8%. Of the participants who met the World Health Organization's diagnostic criteria for diabetes, 31.8% said they had not been previously diagnosed. Similarly, 74.9% of subjects with total cholesterol values above the reference value indicated in the European guidelines on cardiovascular disease said they had not been diagnosed with dyslipidemia, as did 75.5% of those with low-density lipoprotein cholesterol values above the European reference value. The proportion of participants who were not aware that they might be suffering from those disorders was significantly higher among those who reported not having visited their doctor within the last 6 months. CONCLUSION: Further studies should examine whether the use of adapted, more appropriate reference values for elderly populations will help physicians to make early and correct diagnoses and to decide when medical intervention is required. PMID- 22293317 TI - Screening of PAX8 mutations in Chinese patients with congenital hypothyroidism. AB - BACKGROUND: Congenital hypothyroidism (CH) is a neonatal endocrine disease with an incidence of 1:2000 to 1:4000 worldwide. In about 85% of patients CH is secondary to thyroid dysgenesis, but its pathogenesis remains unclear. Thyroid transcription factors, such as paired box transcription factor 8 (PAX8), play an important role in thyroid organogenesis and development. AIM: To screen PAX8 mutations in Chinese CH patients and characterize the features of PAX8 mutations in China. MATERIALS AND METHODS: Blood samples were collected from 300 CH patients in Shandong Province, China, and genomic DNA was extracted from peripheral blood leukocytes. Using PCR and direct sequencing, exon 3 and exon 4 of PAX8 were analyzed. RESULTS: Analysis of PAX8 in 300 CH patients revealed heterozygous missense mutations or variations in two unrelated patients; one was a known missense mutation G92A, resulting in an arginine to histidine substitution at codon 31, the other was a missense variation G122T, resulting in the substitution of a glycine at position 41 by a valine residue. The patient with the R31H mutation had CH with thyroid hypoplasia, while the patient with the G41V variation had CH with a eutopic and normal-sized thyroid gland. CONCLUSION: We report a heterozygous missense mutation and a variation in PAX8 in two out of 300 unrelated Chinese CH patients, showing that the PAX8 mutation rate is very low in CH patients in China. PMID- 22293318 TI - CA 19-9, PSA, oxidative stress and chronic pancreatitis. PMID- 22293319 TI - Intelligence and homosexuality. AB - The origin of preferences and values is an unresolved theoretical problem in behavioural sciences. The Savanna-IQ Interaction Hypothesis, derived from the Savanna Principle and a theory of the evolution of general intelligence, suggests that more intelligent individuals are more likely to acquire and espouse evolutionarily novel preferences and values than less intelligent individuals, but general intelligence has no effect on the acquisition and espousal of evolutionarily familiar preferences and values. Ethnographies of traditional societies suggest that exclusively homosexual behaviour was probably rare in the ancestral environment, so the Hypothesis would predict that more intelligent individuals are more likely to identify themselves as homosexual and engage in homosexual behaviour. Analyses of three large, nationally representative samples (two of which are prospectively longitudinal) from two different nations confirm the prediction. PMID- 22293320 TI - A simple robust method for synthesis of metallic copper nanoparticles of high antibacterial potency against E. coli. AB - A method for preparation of copper nanoparticles (Cu-NPs) was developed by simple reduction of CuCl2 in the presence of gelatin as a stabilizer and without applying stringent conditions like purging with nitrogen. The NPs were characterized by spectrophotometry, dynamic light scattering, x-ray diffraction, transmission electron microscopy, atomic force microscopy and x-ray photoelectron spectroscopy. The particles were about 50-60 nm in size and highly stable. The antibacterial activity of this Cu-NP on Gram-negative Escherichia coli was demonstrated by the methods of agar plating, flow cytometry and phase contrast microscopy. The minimum inhibitory concentration (3.0 ug ml(-1)), minimum bactericidal concentration (7.5 ug ml(-1)) and susceptibility constant (0.92) showed that this Cu-NP is highly effective against E. coli at a much lower concentration than that reported previously. Treatment with Cu-NPs made E. coli cells filamentous. The higher the concentration of Cu-NPs, the greater the population of filamentous cells; average filament size varied from 7 to 20 um compared to the normal cell size of ~2.5 um. Both filamentation and killing of cells by Cu-NPs (7.5 ug ml(-1)) also occurred in an E. coli strain resistant to multiple antibiotics. Moreover, an antibacterial effect of Cu-NPs was also observed in Gram-positive Bacillus subtilis and Staphylococcus aureus, for which the values of minimum inhibitory concentration and minimum bactericidal concentration were close to that for E. coli. PMID- 22293321 TI - The dynamic yin-yang interaction of CXCR4 and CXCR7 in breast cancer metastasis. AB - The contribution of CXCR7 to the tumor microenvironment has introduced a new level of complexity to CXCL12 signaling in breast cancer. In the previous issue of Breast Cancer Research, Hernandez and colleagues delineate the roles of CXCR4 and CXCR7 in tumor invasion and metastasis. The authors demonstrate that co expression of CXCR7 and CXCR4 results in inhibition of CXCL12-mediated invasion, reduced intravasation of tumor cells into the vasculature, and fewer lung metastases compared with parental tumors. The results of this study suggest the combination of small molecule inhibitors of CXCR4 and CXCR7 could dramatically reduce invasion, intravasation, and metastasis and could be highly beneficial for the treatment of invasive breast cancer. PMID- 22293322 TI - Glucose-6-phosphate dehydrogenase (G6PD) mutations database: review of the "old" and update of the new mutations. AB - In the present paper we have updated the G6PD mutations database, including all the last discovered G6PD genetic variants. We underline that the last database has been published by Vulliamy et al. [1] who analytically reported 140 G6PD mutations: along with Vulliamy's database, there are two main sites, such as http://202.120.189.88/mutdb/ and www.LOVD.nl/MR, where almost all G6PD mutations can be found. Compared to the previous mutation reports, in our paper we have included for each mutation some additional information, such as: the secondary structure and the enzyme 3D position involving by mutation, the creation or abolition of a restriction site (with the enzyme involved) and the conservation score associated with each amino acid position. The mutations reported in the present tab have been divided according to the gene's region involved (coding and non-coding) and mutations affecting the coding region in: single, multiple (at least with two bases involved) and deletion. We underline that for the listed mutations, reported in italic, literature doesn't provide all the biochemical or bio-molecular information or the research data. Finally, for the "old" mutations, we tried to verify features previously reported and, when subsequently modified, we updated the specific information using the latest literature data. PMID- 22293323 TI - Relationship between embryo collection results after superovulation treatment of Japanese Black cows and their plasma beta-carotene and vitamin concentrations. AB - The objective of this study was to investigate the relationship between the plasma concentrations of vitamin A (VA), vitamin E (VE) and beta-carotene (BC) during embryo collection in Japanese Black cows that had undergone superovulation treatment and the embryo collection results. Following superovulation treatment in 116 Japanese Black cows, we collected 1317 embryos by nonsurgical means seven days after artificial insemination. The collected embryos were classified into transferable embryos, unfertilized oocytes and degenerated embryos. After embryo collection, we collected blood samples from the cows and measured the plasma concentrations of VA, VE and BC. The cows were then divided into 2 groups depending on the plasma concentration of VA (L and H: < 80 IU/dl and >= 80 IU/dl), VE (L and H: < 150 ug/dl and >= 150 ug/dl) and BC (L and H: < 150 ug/dl and >= 150 ug/dl). As a result, the number of collected embryos in the H group of VE was significantly (P<0.01) higher than that in L groups. Furthermore, the number of transferable embryos was higher (P<0.05) in all VA, VE and BC H groups than in the L groups. The H group for BC showed a high ratio of transferable embryos compared with the L group (P<0.05). Consequently, the present study suggests that the plasma VE and BC concentrations are positively correlated with the embryo collection results. PMID- 22293324 TI - Production of giant mouse oocyte nucleoli and assessment of their protein content. AB - Compared with advanced developmental stage embryos and somatic cells, fully grown mammalian oocytes contain specific nucleolus-like structures (NPB - nucleolus precursor bodies). It is commonly accepted that they serve as a store of material(s) from which typical nucleoli are gradually formed. Whilst nucleoli from somatic cells can be collected relatively easily for further biochemical analyses, a sufficient number of oocyte nucleoli is very difficult to obtain. We have found that isolated oocytes nucleoli fuse very efficiently when contact is established between them. Thus, well visible giant nucleoli can be obtained, relatively easily handled and then used for further biochemical analyses. With the use of colloidal gold staining, we estimated that a single fully grown mouse oocyte nucleolus contains approximately 1.6 ng of protein. We do believe that this approach will accelerate further research aiming at analyzing the composition of oocyte nucleoli in more detail. PMID- 22293325 TI - Q and A: What is a pathogen? A question that begs the point. PMID- 22293326 TI - The role of adherence in virological suppression in patients receiving anti-HBV analogues. AB - BACKGROUND: Although adherence is of major importance in long-term treatments, few studies have been published regarding the use of anti-HBV analogues in clinical practice. The aim of this study was to evaluate adherence to anti-HBV analogues and associated virological suppression. METHODS: A cross-sectional study was performed between 1 January 2009 and 15 July 2009 in Cochin Hospital, Paris, France. It included all patients being treated with anti-HBV analogues for at least three months, who were without coinfection (HIV, HCV or HDV) and who had not received organ transplants. At the time of enrolment, HBV viral load, analogue regimen and self-reported adherence were collected prospectively. Patients were classified as non-adherent, or moderately or totally adherent using a score based on analysis of self-reports. Other data were obtained retrospectively. RESULTS: Among the 190 patients meeting the inclusion criteria, 33% were initially hepatitis B e antigen-positive and 50% had extensive fibrosis or cirrhosis. Pretreatment viral load was 6.0 log IU/ml (median). The median duration of treatment was 52 months. At enrolment, 61%, 32% and 7% of patients were classified as totally adherent, moderately adherent and non-adherent, respectively. Complete virological suppression (HBV DNA<12 IU/ml) was observed in 83% of patients at enrolment. In the multivariate analysis, lack of virological suppression was associated with an increased pretreatment viral load, with no change in analogue regimen and is classified as non-adherent. CONCLUSIONS: Adherence seems to be an independent factor associated with virological suppression during anti-HBV analogue treatment. Therapeutic education and a systematic evaluation of adherence using self-reports should be promoted to assure long-term anti-HBV analogue efficacy in clinical practice. PMID- 22293327 TI - Role of thioredoxin in lung disease. AB - Thioredoxin system is a ubiquitous thiol oxidoreductase system that regulates cellular reduction/oxidation (redox) status. It includes thioredoxin (Trx), thioredoxin reductase (TrxR), and NADPH. Trx plays an essential role in cell function by limiting oxidative stress directly via antioxidant effects and indirectly by proteins interaction with key signal transduction molecules. A variety of signaling molecules have been implicated in the cytoprotection conferred by Trx, such as autophagic proteins, p38 mitogen-activated protein kinase, nuclear factor-kappaB, phosphatidylinositol 3-kinase. Recent studies indicated that Trx may contribute to the pathogenesis of COPD, asthma and lung injury. Enhanced Trx expression or application of recombinant Trx afforded protection in preclinical models of pulmonary tissue injury, which suggested Trx may be used in future therapeutic applications. The focus of this review is on the significance of Trx in various pulmonary diseases, which as a potential therapeutic strategy to protect against oxidative stress and inflammation. PMID- 22293328 TI - Role of serological markers of activated eosinophils in inflammatory bowel diseases. AB - BACKGROUND: Activated eosinophils can infiltrate the intestinal mucosa in patients with inflammatory bowel disease (IBD), and eosinophils are also implicated in the histological damage seen in allergic diseases. AIM: To assess, in a group of patients with IBD in remission or with a mild disease activity, whether serological markers of eosinophil activation, eosinophil cationic protein (ECP) and eosinophil protein X (EPX), are related to evidence of IgE hypersensitivity and to the eosinophilia in gut mucosa. METHODS: Sixty-one patients with IBD (21 Crohn's disease and 40 ulcerative colitis) in remission or with a mild disease activity were screened for IgE hypersensitivity and serological levels of ECP and EPX. Colonic biopsies were taken to assess mucosal eosinophilic infiltration. RESULTS: Skin prick test were positive in 31.1% of the patients with IBD, showing skin reactions to food allergens in 17.7%. Skin prick test findings were unrelated to ECP or EPX levels, or to clinical activity or eosinophil counts in the gut mucosa. A significant correlation was found between ECP and EPX levels (r=0.77; P<0.0001). CONCLUSION: Serological ECP and EPX findings did not correlate with IgE hypersensitivity findings or eosinophilic colonic infiltration in patients with IBD in remission or with mild disease activity. The role of eosinophils in IBD needs to be better characterized in the colonic mucosa, instead of relying on serological tests. PMID- 22293329 TI - Diagnosis and treatment strategies of tuberculous intestinal perforations: a case series. AB - Gastrointestinal tuberculosis (TB) may result in intestinal obstruction and perforation, even after antituberculous therapy has been initiated. Despite surgical intervention tuberculous perforation has a high complication and mortality rate, and it is difficult to predict the subgroup of patients with abdominal TB who progress to perforation. In this study, we retrospectively investigated the clinical features that may predict disease progression in patients in our institution who presented abdominal TB over a 5-year period between January 2006 and August 2011, as well as describe an unreported method of managing tuberculous intestinal perforations when resection with end-to-end anastomosis is unfeasible. Six out of 91 patients (6.6%) with abdominal TB developed perforations. Factors linked with increased complications and mortality were age, comorbidities, multiple perforations and length of time between onset of abdominal symptoms and perforation. Four patients (66.7%) had long histories of abdominal symptoms before perforation. Three patients were receiving or had completed antituberculous therapy before developing perforation. Five patients were managed surgically, two underwent laparostomy as both primary closure and end-to-end anastomosis were deemed too risky. Mortality following perforation was 17%. Patients with prolonged abdominal symptoms, even after antituberculous therapy, should raise suspicion for subacute intestinal obstruction. This should be recognized early and surgical intervention considered in order to prevent mortality secondary to perforation. Laparostomy may be an alternative when resection and end-to-end anastomosis is not possible. PMID- 22293330 TI - Hepatic Methionine-enkephalin may interfere with response to antiviral therapy in chronic hepatitis C. AB - BACKGROUND: The immunoreactivity of methionine-enkephalin (Met-enkephalin), one of the endogenous opioid peptides, is expressed in the liver in different types of chronic diseases. This finding suggests that the liver may be a source of endogenous opioids in disease state. In-vitro studies have shown that morphine, which exerts its effect by binding to opioid receptors, enhances hepatitis C virus replication and that it interferes with the antiviral effects of interferon. Thus, it was hypothesized that liver-derived endogenous opioids, which also bind to opioid receptors, may interfere with the response to antiviral therapy with interferon. AIM: To correlate the expression of Met-enkephalin immunoreactivity (MEIR) in the liver of patients with chronic hepatitis C with their response to treatment with pegylated interferon and ribavirin. METHODS: We sought to investigate the expression of the immunoreactivities of Met-enkephalin and of the delta-opioid receptor 1 (DOR1), to which Met-enkephalin binds, preferentially, in liver samples from 23 patients with chronic hepatitis C who had undergone antiviral therapy. Twelve patients obtained a sustained virological response, and 11 patients were relapsers after or nonresponders to treatment. Among the 12 patients with sustained virological response, one patient (8.3%) expressed MEIR and another one expressed DOR1 immunoreactivity (8.3%), whereas none of the patients expressed both immunoreactivities. Among the group of nonresponders/relapsers, one patient expressed MEIR (9%), two patients expressed DOR1 immunoreactivity (18.2%), and seven patients expressed both (63.6%). The difference between responders and nonresponders in the expression of both immunoreactivities was significantly different (P<0.001). CONCLUSION: Our data are in favor of the hypothesis that enhanced expression of MEIR and DOR1 immunoreactivity correlates with poor response to antiviral therapy that includes interferon. Thus, this study provides a rationale to study the effect of opiate antagonists in combination with antiviral therapy with interferon and ribavirin in patients who express MEIR in the liver and who have not responded to or who have relapsed after treatment with those antiviral medications. PMID- 22293331 TI - Low-dose heparin in the prevention of post endoscopic retrograde cholangiopancreatography pancreatitis: a systematic review and meta-analysis. AB - One of the most frequent and serious complications of endoscopic retrograde cholangiopancreatography (ERCP) is acute pancreatitis. The aim of this study was to evaluate the preventive effect of low-dose heparin (unfractionated or low molecular-weight heparin) on post-ERCP pancreatitis (PEP) and its side-effects by a systematic review and meta-analysis of clinical trials. Searching PubMed and EMBASE, up to August 2011, two independent reviewers systematically identified prospective clinical trials detecting the effect of prophylactic low-dose heparin on the incidence of PEP, severe PEP, and post-ERCP hemorrhage complications. Four clinical trials fulfilled our selection criteria, with three prospective randomized and one nonrandomized. A meta-analysis of these clinical trials was then performed. A total of 1438 patients were included. Meta-analysis of these trials indicated that there was no significant association between the use of heparin and the reduction of PEP [relative risk (RR) 0.67, 95% confidence interval (CI): 0.44-1.03, P=0.07] and severe PEP (RR 0.62, 95% CI: 0.15-2.60, P=0.51). However, low-dose heparin did not increase the incidence of post-ERCP hemorrhage complications (RR 0.84, 95% CI: 0.34-2.03, P=0.69). This meta-analysis did not demonstrate a statistically significant benefit of prophylactic heparin use for the prevention of post-ERCP pancreatitis. More multicenter trials involving a larger number of patients are needed to show a possible prevention effect of PEP from heparin and its related compounds. PMID- 22293332 TI - Hepatectomy for hepatocellular carcinoma patients with macronodular cirrhosis. AB - OBJECTIVE: Patients with hepatocellular carcinoma (HCC) presenting with nonmicronodular or micronodular cirrhosis are usually treated by hepatectomy. The value of resection for patients with hepatitis B virus-related macronodular cirrhosis, however, remains unknown because of potentially fatal complications of this procedure. METHODS: Clinicopathological data were analyzed for 85 resected HCC patients with hepatitis B virus-related macronodular cirrhosis. An additional 255 patients with nonmicronodular and micronodular cirrhosis were randomly selected during the same period as the control group. RESULTS: Compared with nonmicronodular and micronodular cirrhosis patients, macronodular cirrhotic patients exhibited elevated alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase levels, higher Child-Pugh classification, higher indocyanine green retention rate at 15 min (ICG R15), and more number of total complications. No significant differences were observed between the two groups with regard to major complications, mortality, overall survival, and recurrence free survival. The morbidity rate was relatively low in patients exhibiting low ICG R15 (<10%). Cox analysis identified small tumors (<= 5 cm) and radical resection as independent prognostic factors that could predict long-term overall survival. Radical resection can result in high recurrence-free survival in macronodular cirrhotic patients. CONCLUSION: Resection is safe for macronodular cirrhotic HCC patients, and radical resection provides a positive outcome. Small sized patients are good candidates for hepatectomy. Macronodular cirrhosis should not rule out hepatectomy in patients with low ICG R15. PMID- 22293333 TI - Epidermal growth factor gene polymorphism 61A/G in patients with chronic liver disease for early detection of hepatocellular carcinoma: a pilot study. AB - BACKGROUND: Overexpression of epidermal growth factor (EGF) in the liver induces transformation into hepatocellular carcinoma (HCC) in animal models. Polymorphisms in the EGF gene modulate EGF levels. OBJECTIVES: To evaluate the effect of EGF gene single nucleotide polymorphism and to assess its correlation with the risk of HCC in patients with chronic liver diseases. PATIENTS AND METHODS: The present study included 80 participants divided into four groups: group 1 included 20 asymptomatic healthy control volunteers, group 2 included 20 patients with chronic hepatitis C viral (HCV) infection, group 3 included 20 patients with liver cirrhosis, and group 4 included 20 patients with HCC. For all participants, the following investigations were performed: routine laboratory investigations including complete blood count, liver function tests, sero markers of hepatitis viruses HBsAg, HCV-RNA by quantitative polymerase chain reaction, and alpha-fetoprotein. DNA was extracted from whole blood for detection of single nucleotide polymorphism of the EGF by polymerase chain reaction, followed by restriction fragment length polymorphism. RESULTS: We found a significant difference between both patients with HCC and HCV versus controls in terms of the G carrier (GG and GA; 80 vs. 40%, P<0.05). In addition, the cirrhotic and chronic hepatitis C patients with GG had three-fold and 2.3-fold odds ratio for developing HCC, respectively. CONCLUSION: The EGF 61GG genotype might be associated with a high risk for the development of HCC in Egyptian patients with chronic liver disease. PMID- 22293334 TI - Physical education combined with pedometer use is associated with better glucose tolerance among overweight/obese with impaired glucose tolerance; no benefit for education alone. PMID- 22293335 TI - Telaprevir triple combination therapy, and dual peginterferon alpha-2a/ribavirin therapy for 24 weeks for those with rapid-early response is not inferior to 48 weeks of therapy for treatment-naive patients with genotype 1 hepatitis C virus infection. PMID- 22293336 TI - Overweight and obese individuals following either commercial or primary care-led weight loss programmes achieve significant weight loss at the end of the 12-week programme, but only the commercial programmes studied had sustained effect to 1 year. PMID- 22293337 TI - Cardiovascular risks of stopping antiplatelet therapy before non-cardiac surgery for patients with coronary stents. PMID- 22293338 TI - Early introduction of allergenic food is not associated with increased report of wheeze or eczema. PMID- 22293339 TI - Patients on three times-weekly haemodialysis have increased mortality during the long, 2-day interdialytic interval. PMID- 22293340 TI - Non-fasting blood testing for lipid screening in children result in statistically significant, but not clinically significant, changes in lipid levels. PMID- 22293341 TI - beta-amyloid42 induces desensitization of CXC chemokine receptor-4 via formyl peptide receptor in neural stem/progenitor cells. AB - The deposition of beta-amyloid (Abeta) plaques and progressive loss of neurons are two main characteristics of Alzheimer's disease (AD). Supplement of neural stem/progenitor cells (NSPCs) is a promising strategy for repair of the neurodegenerative diseases. However, hostile microenvironment of neurodegenerative brain is harmful for the neuroregeneration. Abeta(42) promoted the proliferation of NSPCs. Moreover, Abeta(42) (10-1000 nM) promoted the migration of NSPCs in a dose-dependent manner. The attraction of NSPCs toward Abeta(42) was significantly offset by 10 MUM cyclosporin H, a potent and selective formyl peptide receptor antagonist. After incubation with Abeta(42) for 9 d, the migration ability of NSPCs was significantly decreased (p<0.05). The expression of formyl peptide receptor (FPR) and CXC chemokine receptor-4 (CXCR4) were significantly decreased in NSPCs. The expression of G protein-coupled receptor kinase 2 (GRK2) was up-regulated on the membrane of NSPCs correspondingly. Our results suggested that Abeta(42) decreases the migratory capacity of NSPCs by FPR heterologous desensitization after long time incubation, and GRK2 in NSPCs may be responsible for the damaged migratory capacity. PMID- 22293342 TI - A novel drug delivery system of oral curcumin markedly improves efficacy of treatment for heart failure after myocardial infarction in rats. AB - Curcumin is an inhibitor of p300 histone acetyltransferase activity, which is associated with the deterioration of heart failure. We reported that native curcumin, at a dosage of 50 mg/kg, prevented deterioration of the systolic function in rat models of heart failure. To achieve more efficient oral pharmacological therapy against heart failure by curcumin, we have developed a novel drug delivery system (DDS) which markedly increases plasma curcumin levels. At the dosage of 0.5 mg/kg, DDS curcumin but not native curcumin restored left ventricular fractional shortening in post-myocardial infarction rats. Thus, our DDS strategy will be applicable to the clinical setting in humans. PMID- 22293343 TI - Pre-treatment with curcumin enhances plasma concentrations of losartan and its metabolite EXP3174 in rats. AB - The study was carried out in the Wistar rats to investigate the effect of curcumin pre-treatment on the pharmacokinetics of the hypertension-treating drug losartan and its metabolite EXP3174 following single oral administration. In the treatment group, rats were gavaged with losartan 10 mg/kg after repeat oral doses of curcumin (100 mg/kg, for 7 d), while rats in the control group were administrated only with the same dose losartan. The results showed that curcumin significantly increased the plasma concentrations of losartan and its metabolite EXP3174. The present study implicated the existence of herb-drug interaction between curcumin and losartan, and further evaluation of the possible interaction during curcumin administration needs to be considered. PMID- 22293344 TI - Mutual inhibition between carvedilol enantiomers during racemate glucuronidation mediated by human liver and intestinal microsomes. AB - Carvedilol is administered orally as a racemic mixture of R(+)- and S(-) enantiomers for treatment of angina pectoris, hypertension and chronic heart failure. We have reported that enzyme kinetic parameters for carvedilol glucuronidation by human liver microsomes (HLM) differed greatly depending on the substrate form, namely, racemic carvedilol and each enantiomer. These phenomena were thought to be caused by mutual inhibition between carvedilol enantiomers during racemate glucuronidation. The aim of this study was to clarify the mechanism of these phenomena in HLM and human intestinal microsomes (HIM) and its relevance to uridine 5'-diphosphate (UDP)-glucuronosyl transferase (UGT) 1A1, UGT2B4 and UGT2B7, which mainly metabolize carvedilol directly in phase II enzymes. HLM apparently preferred metabolizing (S)-carvedilol to (R)-carvedilol in the racemate, but true activities of HLM for both glucuronidation were approximately equal. By determination of the inhibitory effects of (S)-carvedilol on (R)-carvedilol glucuronidation and vice versa, it was shown that (R) carvedilol glucuronidation was more easily inhibited than was (S)-carvedilol glucuronidation. UGT2B7 was responsible for (S)-carvedilol glucuronidation in HLM. Ratios of contribution to (R)-carvedilol glucuronidation were approximately equal among UGT1A1, UGT2B4 and UGT2B7. However, enzyme kinetic parameters were different between the two lots of HLM used in this study, depending on the contribution ratio of UGT2B4, in which (R)-glucuronidation was much more easily inhibited by (S)-carvedilol than was (S)-glucuronidation by (R)-carvedilol. Meanwhile, HIM preferred metabolizing (R)-carvedilol, and this tendency was not different between the kinds of substrate form. PMID- 22293345 TI - Neuroprotective capabilities of Tanshinone IIA against cerebral ischemia/reperfusion injury via anti-apoptotic pathway in rats. AB - Danshen, derived from the dried root or rhizome of Salviae miltiorrhizae BGE., has Tanshinone IIA (TSA) as one of its active ingredients. Recent reports have shown that TSA can inhibit the apoptosis induced by serum withdrawal or ethanol in cultured PC12 cells. However, whether TSA has any neuroprotective effect remains unknown. In this study, we investigated the effects of TSA on cerebral apoptosis induced by middle cerebral artery occlusion (MCAO) in which cerebral ischemia had been induced 2 h earlier. Twenty-four hours after reperfusion, the rats were assessed for infarct volume etc. Intraperitoneal administration of 25 and 40 mg/kg TSA 10 min after MCAO significantly diminished infarct volume and brain water content and improved neurological deficits in a dose-dependent manner. The 25 mg/kg dosage was more effective. Treatment with 25 mg/kg TSA significantly improved symptoms and reduce infarct volume at different points in time, of which 10 min after MCAO was the most significant. Nissl-staining and HE staining of the 25 mg/kg TSA group were more appreciable in terms of improvement relative to the vehicle group in the infarct core. TSA of dosage 25 mg/kg significantly decreased the expression of cleaved caspase-3 protein and increased the expression of B-cell lymphoma 2 (bcl-2) protein in the ischemic cortex. Fewer terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling (TUNEL)-positive cells were found in the penumbra of the treated group, but they were significantly more common in the vehicle group. We here conclude that the neuroprotective effects of TSA against focal cerebral ischemic/reperfusion injury are likely to be related to the attenuation of apoptosis. PMID- 22293346 TI - The molecular mechanisms of the hepatoprotective effect of gomisin A against oxidative stress and inflammatory response in rats with carbon tetrachloride induced acute liver injury. AB - Oxidative damage and inflammation are implicated in the pathogenesis of liver injury and fibrosis. In the present study, we investigated the molecular mechanism by which gomisin A conferred a hepatoprotective effect, focusing on its antioxidant and anti-inflammatory effects using rats with carbon tetrachloride (CCl(4))-induced acute liver injury. Pretreatment with gomisin A prior to the administration of CCl(4) markedly prevented an increase in alanine aminotransferase, aspartate aminotransferase, and histological hepatic lesions. Gomisin A was also associated with a decrease in hepatic lipid peroxidation, and increased superoxide dismutase activity, suggesting that gomisin A has an antioxidant effect. In addition gomisin A treatment ameliorated mRNA levels of CCl(4)-induced inflammatory mediators, including tumor necrosis factor-alpha, interleukin-1beta and inducible nitric oxide (NO) synthase, and the protein levels of transcriptional upregulator nuclear factor kappa B (NF-kappaB) and phospho-inhibitor of NF-kappaB (IkappaB). Furthermore, alpha-smooth muscle actin (alpha-SMA), a myofibroblast marker, was also inhibited by gomisin A treatment. These results suggest that gomisin A inhibits the oxidative stress and activation of NF-kappaB, leading to down-regulation of pro-inflammatory mediators and amelioration of fibrogenesis. PMID- 22293347 TI - Kefiran suppresses antigen-induced mast cell activation. AB - Kefir is a traditional fermented milk beverage produced by kefir grains in the Caucasian countries. Kefiran produced by Lactobacillus kefiranofaciens in kefir grains is an exopolysaccharide having a repeating structure with glucose and galactose residues in the chain sequence and has been suggested to exert many health-promoting effects such as immunomodulatory, hypotensive, hypocholesterolemic activities. Here we investigated the effects of kefiran on mast cell activation induced by antigen. Pretreatment with kefiran significantly inhibited antigen-induced Ca(2+) mobilization, degranulation, and tumor necrosis factor-alpha production in bone marrow-derived mast cells (BMMCs) in a dose dependent manner. The phosphorylation of Akt, glycogen synthase kinase 3beta, and extracellular signal-regulated kinases (ERKs) after antigen stimulation was also suppressed by pretreatment of BMMCs with kefiran. These findings indicate that kefiran suppresses mast cell degranulation and cytokine production by inhibiting the Akt and ERKs pathways, suggesting an anti-inflammatory effect for kefiran. PMID- 22293348 TI - Characterization of fatty acid profile in the liver of SHR/NDmcr-cp (cp/cp) rats, a model of the metabolic syndrome. AB - The fatty acid profile of hepatic lipid in spontaneously hypertensive rats (SHR)/NDmcr-cp (cp/cp) rats (SHR/NDcp), which offer an animal model of the metabolic syndrome, was characterized by comparing those in Wistar Kyoto rats (WKY), SHR, stroke-prone spontaneously hypertensive rats (SHRSP) and SHR/NDmcr-cp (+/+) rats (SHR/ND+) . Hierarchical clustering analysis revealed that SHR/NDcp and the other four strains and/or substrains of rats were clearly disparate in fatty acid profile of hepatic lipid and that the disparity observed was due to the drastic increases in the mass of monounsaturated fatty acids, especially palmitoleic acid and oleic acid, in the liver of SHR/NDcp. Activities of stearoyl CoA desaturase (SCD) and palmitoyl-CoA chain elongase in hepatic microsomes of SHR/NDcp were markedly higher than those of WKY, SHR, SHRSP and SHR/ND+. Activities of palmitoleoyl-CoA chain elongase in the liver of SHR/NDcp were also higher, but to a lesser extent. mRNA levels of SCD1 and elongation of very long chain fatty acids (Elovl6), but not Elovl5, in the liver of SHR/NDcp were remarkably higher than those of the other four groups of rats. These results suggest that the enhanced expressions of SCD1 and Elovl6 induced abnormalities in fatty acid profile in the liver of SHR/NDcp. PMID- 22293349 TI - Influence of skin thickness on the in vitro permeabilities of drugs through Sprague-Dawley rat or Yucatan micropig skin. AB - The purpose of this study was to clarify the influence of skin thickness on the in vitro permeabilities of 3 model drugs with different physicochemical properties (nicorandil (NR), isosorbide dinitrate (ISDN) and flurbiprofen (FP)) through Sprague-Dawley rat (rat) or Yucatan micropig (YMP) skin. Intact, dermis split, stratum corneum-stripped or stratum corneum-stripped and dermis-split rat or YMP skin (rat skin thickness: approximately 0.4, 0.9 or 1.2 mm; YMP skin thickness: approximately 0.4, 0.9, 1.8 or 2.8 mm) were set in Franz-type diffusion cells to determine the permeation rate, lag time and resistance ratio of the viable epidermis and dermis against whole skin (R(ved)/R(tot)) of the drugs. The YMP skin permeabilities of the drugs decreased with an increase in the skin thickness, and significant differences were observed in the permeation rates and lag times between intact and dermis-split (0.4 mm) YMP skins. The decreases in the permeabilities of the drugs through the YMP skin were larger than those through the rat skin. The influence of resistances of ISDN and FP through the dermis-split rat or YMP skin was greater at 0.9 mm skin thickness than 0.4 mm skin thickness. The R(ved)/R(tot) values for the YMP skins were relatively large for lipophilic drugs (ISDN and FP), and these ratios increased with an increase in the dermis thickness. These results suggest that in vitro skin permeation studies must be done using dermis-split (0.4 mm) skin with the thinnest dermis for predicting in vivo human percutaneous absorption rate. PMID- 22293350 TI - The use of an artificial skin model to study transdermal absorption of drugs in inflamed skin. AB - Studies on drug disposition in inflamed skin are important for safe and effective application of topical drugs. Here, the absorption of flurbiprofen (FP) through inflamed skin was examined in vivo and in a skin-mimicking artificial model system. The model skin system consisted of a silicone membrane acting as a model stratum corneum, laminated dialysis membranes acting as a model of viable skin, and 2 microdialysis probes-one used for determination of FP concentration and one acting as a model vessel. This model system could be used for quantitative evaluation of complicated permeation processes. In the in vivo experiments, FP absorption was suppressed in rats with inflamed skin induced by an intracutaneous injection of a mixed solution of lambda-carrageenan, zymosan, and casein. Bovine serum albumin solution was placed between the dialysis membranes in the model skin system to mimic protein leaching in skin; the results suggested that the delayed absorption of FP in inflamed skin was due to binding to serum proteins leaching in the tissue. Such a combination of in vivo experiments and a model skin system is useful for understanding complex phenomena in inflamed and damaged skin and reduces experimental animal use. PMID- 22293351 TI - Matrix metalloproteinase-1 inhibitory activities of Morinda citrifolia seed extract and its constituents in UVA-irradiated human dermal fibroblasts. AB - The objective of this study was to examine whether a 50% ethanolic extract (MCS ext) of the seeds of Morinda citrifolia (noni) and its constituents have matrix metalloproteinase-1 (MMP-1) inhibitory activity in UVA-irradiated normal human dermal fibroblasts (NHDFs). The MCS-ext (10 MUg/mL) inhibited MMP-1 secretion from UVA-irradiated NHDFs, without cytotoxic effects, at 48 h after UV exposure. The ethyl acetate-soluble fraction of MCS-ext was the most potent inhibitor of MMP-1 secretion. Among the constituents of the fraction, a lignan, 3,3' bisdemethylpinoresinol (1), inhibited the MMP-1 secretion at a concentration of 0.3 MUM without cytotoxic effects. Furthermore, 1 (0.3 MUM) reduced the level of intracellular MMP-1 expression. Other constituents, namely americanin A (2), quercetin (3) and ursolic acid (4), were inactive. To elucidate inhibition mechanisms of MMP-1 expression and secretion, the effect of 1 on mitogen activated protein kinases (MAPKs) phosphorylation was examined. Western blot analysis revealed that 1 (0.3 MUM) reduced the phosphorylations of p38 and c-Jun N-terminal kinase (JNK). These results suggested that 1 suppresses intracellular MMP-1 expression, and consequent secretion from UVA-irradiated NHDFs, by down regulation of MAPKs phosphorylation. PMID- 22293352 TI - Natural vanadium-containing Jeju groundwater inhibits immunoglobulin E-mediated anaphylactic reaction and suppresses eicosanoid generation and degranulation in bone marrow derived-mast cells. AB - The high-affinity receptor for immunoglobulin E (IgE) (FcepsilonRI)-mediated activation of mast cells plays an important role in various allergic diseases. To assess the anti-allergic activity of natural vanadium-containing Jeju groundwater (JW), an in vivo passive cutaneous anaphylaxis (PCA) animal model and in vitro mouse bone marrow-derived mast cells (BMMCs) was used. JW inhibited cyclooxygenase-2 (COX-2)-dependent prostaglandin D(2) (PGD(2)) generation in a dose-dependent manner, with a concomitant reduction of COX-2 protein expression in IgE-induced BMMCs. In addition, JW inhibited 5-lipoxygenase (5-LOX)-dependent generation of leukotriene C(4) (LTC(4)) as well as degranulation in a dose dependent manner. These results demonstrate that JW has dual COX-2/5-LOX inhibitory activity. In addition, vanadium pentoxide (V(2)O(5)), which is the major vanadium component of JW, also inhibited PGD(2) and LTC(4) generation as well as degranulation in IgE-induced BMMCs. Furthermore, oral administration of JW dose-dependently inhibited mast cell-dependent passive anaphylactic reaction in IgE-sensitized mice. Taken together, these results suggest that JW may be useful in regulating mast cell-mediated allergic response through the suppression of eicosanoid generation and degranulation in mast cells. PMID- 22293353 TI - Immature Citrus sunki peel extract exhibits antiobesity effects by beta-oxidation and lipolysis in high-fat diet-induced obese mice. AB - The peel of Citrus sunki HORT. ex TANAKA has been widely used in traditional Asian medicine for the treatment of many diseases, including indigestion and bronchial asthma. In this study, we investigated the antiobesity activity of immature C. sunki peel extract (designated CSE) using high-fat diet (HFD)-induced obese C57BL/6 mice and mature 3T3-L1 adipocytes. In the animal study, body weight gain, adipose tissue weight, serum total cholesterol, and triglyceride in the CSE administered group decreased significantly compared to the HFD group. Also, CSE supplementation reduced serum levels of glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, and lactate dehydrogenase. Moreover, it significantly decreased the accumulation of fatty droplets in liver tissue, suggesting a protective effect against HFD-induced hepatic steatosis. Dietary supplementation with CSE reversed the HFD-induced decrease in the phosphorylation levels of AMP activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), which are related to fatty acid beta-oxidation, in the epididymal adipose tissue. Also, CSE increased AMPK and ACC phosphorylation in mature 3T3-L1 adipocytes. CSE also enhanced lipolysis by phosphorylation of cAMP-dependent protein kinase (PKA) and hormone-sensitive lipase (HSL) in mature 3T3-L1 adipocytes. These results suggest that CSE had an antiobesity effect via elevated beta-oxidation and lipolysis in adipose tissue. PMID- 22293354 TI - Effect of Conclevan on endurance capacity in mice. AB - The purpose of this study was to clarify the anti-fatigue effect of Conclevan, which is mainly composed of liver hydrolysate, via a forced swimming test using mice. Conclevan was administered to mice for 6 weeks, and a forced swimming test was conducted to measure swimming time. After six weeks, the blood ammonia and glutamine concentrations were measured. In the Conclevan administration group, swimming time increased significantly compared to the swimming control group. In the swimming control group, an increase in blood ammonia and a decrease in blood glutamine were observed, relative to the non-swimming control group. In the Conclevan administration group, the increased blood ammonia and decreased blood glutamine induced by swimming were significantly reduced, compared to the swimming control group. The mRNA expression levels of the hepatic enzymes of the urea cycle (carbamoyl-phosphate synthetase, argininosuccinate synthetase, and arginase) and glutamine synthesis (glutamate dehydrogenase and glutamine synthetase) were significantly increased in the Conclevan administration group, compared to the swimming control group. The results of this study demonstrated the anti-fatigue effects of Conclevan. This product may inhibit an increase in the fatigue-inducing ammonia concentration in the blood by increasing the expression of hepatic enzymes, which convert ammonia to urea, leading to increased swimming time. In addition, Conclevan may prolong swimming time by increasing the hepatic synthesis of glutamine, which is an important amino acid for supplying energy in muscles. PMID- 22293355 TI - Pharmacokinetic and pharmacodynamic evaluation of the anti-cataract effect of eye drops containing disulfiram and low-substituted methylcellulose using ICR/f rats as a hereditary cataract model. AB - We attempted to develop anti-cataract eye drops using disulfiram (DSF) and low substituted methylcellulose (MC), and evaluated their anti-cataract effect in terms of the lens opacification vs. age-profile curves using a one-exponential equation. The eye drops were prepared using 0.5% DSF and 2% MC (DSF eye drops), and ICR/f rats, a recessive-type hereditary cataractous strain, were used as the experimental model. Gelation of DSF eye drops containing MC was first observed at about 35 degrees C, close to body temperature. In in vivo transcorneal penetration experiments using rabbit corneas, only diethyldithiocarbamate (DDC) was detected in the aqueous humor, while DSF was not detected. The DDC penetration level of DSF eye drops containing MC was approximately 1.3-fold higher than that of DSF eye drops. The opacification rate constant (k) of ICR/f rat instilled with DSF eye drops with or without MC was lower, and the initial time of opacification (tau) was longer than those of ICR/f rats instilled with saline. Furthermore, the k of ICR/f rats instilled with DSF eye drops with MC was lower than that of ICR/f rats instilled with DSF eye drops without MC. In conclusion, the analysis of kinetic parameters including k and tau using a one exponential equation provided useful information for clarifying the anti-cataract effect of eye drops. ICR/f rats instilled with DSF eye drops using a low substituted MC-based drug delivery system demonstrated a delay in cataract development, probably resulting from an increase in the retention of DSF eye drops on the cornea. PMID- 22293356 TI - Involvement of interleukin-1 in lead nitrate-induced hypercholesterolemia in mice. AB - Hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and cholesterol 7alpha hydroxylase (Cyp7a1) are rate-limiting enzymes for cholesterol biosynthesis and catabolism, respectively. Involvement of inflammatory cytokines, particularly interleukin-1 (IL-1), in alterations of HMGR and Cyp7a1 gene expression during development of lead nitrate (LN)-induced hypercholesterolemia was examined in IL 1alpha/beta-knockout (IL-1-KO) and wild-type (WT) mice. Lead nitrate treatment of WT mice led to not only a marked downregulation of the Cyp7a1 gene at 6-12 h, but also a significant upregulation of the HMGR gene at 12 h. However, such changes were not observed at significant levels in IL-1-KO mice, although a slight, transient downregulation of the Cyp7a1 gene and a minimal upregulation of the HMGR gene occurred at 6 h and 24 h, respectively. Consequently, LN treatment led to development of hypercholesterolemia at 24 h in WT mice, but not in IL-1-KO mice. Furthermore, in WT mice, significant LN-mediated increases were observed at 3-6 h in hepatic IL-1 levels, which can modulate gene expression of Cyp7a1 and HMGR. These findings indicate that, in mice, LN-mediated increases in hepatic IL 1 levels contribute, at least in part, to altered expressions of Cyp7a1 and HMGR genes, and eventually to hypercholesterolemia development. PMID- 22293357 TI - Intravenously administered 2'-deoxycytidine suppresses mouse myeloma tumor growth. AB - We examined the in vivo effects of intravenously administered 2'-deoxycytidine (dCyd) on tumor growth and survival time in mice bearing SP2/0-Ag14 (SP2/0) myeloma tumors. Administration of dCyd tended to decrease the tumor volume and significantly decreased the tumor weight. A single intravenous administration of dCyd significantly increased survival time of the tumor-bearing mice. The effect of dCyd on tumor growth was maintained for at least 1 week after the final administration. The net amount of dCyd in the kidney, liver, and spleen of the tumor-bearing mice increased 2.5 to 5.3 fold compared with the amount in non tumor-bearing mice. Our results suggest that the increase in dCyd in the mice inoculated SP2/0 myeloma cells plays an important role for the growth suppression of the tumor. PMID- 22293358 TI - Cytotoxicity of the polymerization agent, 2-methyl-4'-(methylthio)-2 morpholinopropiophenone on human monocytes. AB - This is the first study to detect 2-methyl-4'-(methylthio)-2 morpholinopropiophenone (MTMP) from an intravenous injection bag solution by GC MS. In previous studies, several other photoinitiators were reported to be very cytotoxic. Therefore, we theorized that photoinitiators such as MTMP might also have adverse cellular effects. The purpose of this study was to quantitate the amounts of contaminants from plastic containers such as those used for peripheral parenteral nutrition and to determine the cytotoxicity of such extracts on human monocytes. The sample extraction procedure for GC-MS analysis involved a liquid phase extraction. The solvent was evaporated under a stream of nitrogen at 50 degrees C. The residue was dissolved in n-hexane and injected into a GC-MS. Normal human peripheral blood mononuclear cells (PBMC), isolated from the buffy coat by centrifugation, were suspended in RPMI 1640 medium supplemented with 10% (v/v) heat-inactivated fetal calf serum. In the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay, cells (1*10(4)) were treated with MTMP for 24 h or 48 h at 37 degrees C. From the GC-MS analysis, 5.62 +/- 1.03 MUg/mL of MTMP was found in the BFLUID((r)) Injection 500 mL solution. In the MTT assay, MTMP decreased cell viability in a dose-dependent manner for both the 24 h and 48 h incubation periods. Our findings suggest that photoinitiators could promote adverse effects in patients. Future studies will clarify the possible health risks of photoinitiator accumulation in human cells. PMID- 22293359 TI - Anti-glycation effect of gold nanoparticles on collagen. AB - Gold nanoparticles (GNPs) have been reported to exhibit a variety of biological effects including anti-inflammatory and anti-oxidant activities. The extent of an in vitro glycation reaction mixture of collagen and glycolaldehyde was assayed to investigate the inhibition of glycolaldehye-derived advanced glycation end products (glycol-AGEs) formation with GNPs in collagen, which is a major protein component of the human dermis. GNP-treated collagen showed significantly less glycation (56.3 +/- 4.2%) than an untreated glycation control. Moreover, GNP treated glycation in a collagen lattice model significantly decreased the AGEs distribution in the model system. Taken together, these results suggest that GNPs have the potential for use in the prevention of glycation-induced skin aging. PMID- 22293360 TI - Genotype distributions and allele frequencies of possible major depressive disorder-associated single nucleotide polymorphisms, cyclic adenosine monophosphate response element binding protein 1 rs4675690 and Piccolo rs2522833, in a Japanese population. AB - It is known that the onset of major depressive disorder (MDD) would be associated with genetic factors. To investigate the susceptibility to psychiatric disorders, e.g. MDD, schizophrenia etc., it is necessary to compare the genetic differences of objective polymorphisms between in patients and in relative contol subjects. Recently, an increasing number of studies focused on the role of cyclic adenosine monophosphate response element binding protein 1 (CREB1) and Piccolo (PCLO) on MDD. However, there was no report about genetic characterization of polymorphisms in between MDD patients and healthy subjects in Japanese population. We analized genotype distributions and allele frequencies of CREB1 rs4675690 and PCLO rs2522833 polymorphisms in 267 Japanese subjects, respectively. In CREB1 rs4675690, C allele frequency (0.41) was lower than T allele (0.59). While in PCLO rs2522833, A allele frequency (0.45) was lower than C allele (0.55). Our findings may be useful for investigating the genetic factors concerning the susceptibility to MDD in Japanese population. PMID- 22293361 TI - Possible involvement of ubiquitin ligase HRD1 insolubilization in amyloid beta generation. AB - Endoplasmic reticulum (ER)-associated degradation (ERAD) selectively retro transports and degrades unfolded proteins accumulated in the ER. We have demonstrated that the ubiquitin ligase HRD1 involved in ERAD was significantly decreased in the cerebral cortex of Alzheimer's disease patients. Furthermore, the HRD1 level was negatively correlated with amyloid beta (Abeta) production levels. Here we found that the HRD1 protein level decrease was due to its insolubilization. Moreover, these protein levels extracted from detergent insoluble fraction were positively correlated with those of SEL1L and Abetas (Abeta40 and Abeta42). Thus, the insolubilization-induced decrease in the HRD1 and SEL1L levels might involve in Abeta generation. PMID- 22293362 TI - Implementing a stepped-care approach in primary care: results of a qualitative study. AB - BACKGROUND: Since 2004, 'stepped-care models' have been adopted in several international evidence-based clinical guidelines to guide clinicians in the organisation of depression care. To enhance the adoption of this new treatment approach, a Quality Improvement Collaborative (QIC) was initiated in the Netherlands. METHODS: Alongside the QIC, an intervention study using a controlled before-and-after design was performed. Part of the study was a process evaluation, utilizing semi-structured group interviews, to provide insight into the perceptions of the participating clinicians on the implementation of stepped care for depression into their daily routines. Participants were primary care clinicians, specialist clinicians, and other healthcare staff from eight regions in the Netherlands. Analysis was supported by the Normalisation Process Theory (NPT). RESULTS: The introduction of a stepped-care model for depression to primary care teams within the context of a depression QIC was generally well received by participating clinicians. All three elements of the proposed stepped care model (patient differentiation, stepped-care treatment, and outcome monitoring), were translated and introduced locally. Clinicians reported changes in terms of learning how to differentiate between patient groups and different levels of care, changing antidepressant prescribing routines as a consequence of having a broader treatment package to offer to their patients, and better working relationships with patients and colleagues. A complex range of factors influenced the implementation process. Facilitating factors were the stepped-care model itself, the structured team meetings (part of the QIC method), and the positive reaction from patients to stepped care. The differing views of depression and depression care within multidisciplinary health teams, lack of resources, and poor information systems hindered the rapid introduction of the stepped-care model. The NPT constructs 'coherence' and 'cognitive participation' appeared to be crucial drivers in the initial stage of the process. CONCLUSIONS: Stepped care for depression is received positively in primary care. While it is difficult for the implementation of a full stepped-care approach to occur within a short time frame, clinicians can make progress towards achieving a stepped-care approach, particularly within the context of a QIC. Creating a shared understanding within multidisciplinary teams of what constitutes depression, reaching a consensus about the content of depression care, and the division of tasks are important when addressing the implementation process. PMID- 22293363 TI - Vitamin D supplementation and endothelial function in vitamin D deficient HIV infected patients: a randomized placebo-controlled trial. AB - BACKGROUND: Studies suggest that vitamin D deficiency is a risk factor for cardiovascular disease and diabetes. Vitamin D deficiency is prevalent in HIV patients but the effect of vitamin D supplementation on cardiovascular risk in this population is unknown. METHODS: We conducted a randomized, double-blind, placebo-controlled trial among 45 HIV-infected adults in Cleveland (OH, USA) on stable antiretroviral therapy with durable virological suppression and a baseline serum 25-hydroxyvitamin D level of <=20 ng/ml. Participants were randomized 2:1 to vitamin D3 4,000 IU daily or placebo for 12 weeks. The primary outcome was a change in flow-mediated brachial artery dilation (FMD). RESULTS: Baseline demographics were similar except for age (vitamin D versus placebo, mean +/-sd 47 +/-8 versus 40 +/-10 years; P=0.009). Both groups had reduced FMD at baseline (median values 2.9% [IQR 1.6-4.8] for vitamin D versus 2.5% [IQR 1.7-6.4] for placebo; P=0.819). Despite an increase in the concentration of serum 25 hydroxyvitamin D from baseline to 12 weeks (5.0 ng/ml [IQR -0.9-7.4] versus -1.9 ng/ml [IQR -4.0-0.1] for vitamin D versus placebo, respectively; P=0.003), there was no difference in FMD change (0.55% [IQR -1.05-2.13] versus 0.29% [IQR -1.61 1.77]; P=0.748). Vitamin D supplementation was associated with a decrease in total and non-high-density lipoprotein cholesterol, and an increase in indices of insulin resistance. CONCLUSIONS: Among HIV-infected individuals with vitamin D deficiency, supplementation with 4,000 IU vitamin D3 daily for 12 weeks modestly improved vitamin D status and cholesterol but worsened insulin resistance without change in endothelial function. The mechanisms of resistance to standard doses of vitamin D and the complex role of vitamin D in glucose metabolism in this population require further investigation. PMID- 22293364 TI - Synthesis and characterization of ultra-small magnetic FeNi/G and NiCo/G nanoparticles. AB - Ultra-small magnetic nanoparticles consisting of NiCo and FeNi alloys enclosed within graphitic shells (NiCo/G and FeNi/G) have been synthesized. The particles, which retained the face centered cubic (fcc) symmetry of the original bulk metals, together with the graphitic coating were characterized by means of aberration corrected scanning transmission electron microscopy (STEM), obtaining mean particle sizes of 2.6 nm and 6.2 nm for NiCo/G and FeNi/G, respectively. Due to the enhancement of the thermal stability by the graphite shell, the graphite coated FeNi and NiCo were stable under oxygen atmosphere up to 170 degrees C. The effectiveness of the graphite shell was confirmed when unprotected bimetallic FeNi and NiCo were prepared and chemical characterization revealed that more than 60 at.% of the samples was oxygen due to the massive oxidation of the bimetallic nanoparticles. PMID- 22293365 TI - Do differences in blood pressure between arms matter? PMID- 22293366 TI - WHO's relationship with the Stop TB Partnership. PMID- 22293367 TI - Will increased funding for neglected tropical diseases really make poverty history? PMID- 22293368 TI - WHO's relationship with the Stop TB Partnership. PMID- 22293369 TI - Association of a difference in systolic blood pressure between arms with vascular disease and mortality: a systematic review and meta-analysis. AB - BACKGROUND: Differences in systolic blood pressure (SBP) of 10 mm Hg or more or 15 mm Hg or more between arms have been associated with peripheral vascular disease and attributed to subclavian stenosis. We investigated whether an association exists between this difference and central or peripheral vascular disease, and mortality. METHODS: We searched Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane, and Medline In Process databases for studies published before July, 2011, showing differences in SBP between arms, with data for subclavian stenosis, peripheral vascular disease, cerebrovascular disease, cardiovascular disease, or survival. We used random effects meta analysis to combine estimates of the association between differences in SBP between arms and each outcome. FINDINGS: We identified 28 eligible studies for review, 20 of which were included in our meta-analyses. In five invasive studies using angiography, mean difference in SBP between arms was 36.9 mm Hg (95% CI 35.4-38.4) for proven subclavian stenosis (>50% occlusion), and a difference of 10 mm Hg or more was strongly associated with subclavian stenosis (risk ratio [RR] 8.8, 95% CI 3.6-21.2). In non-invasive studies, pooled findings showed that a difference of 15 mm Hg or more was associated with peripheral vascular disease (nine cohorts; RR 2.5, 95% CI 1.6-3.8; sensitivity 15%, 9-23; specificity 96%, 94 98); pre-existing cerebrovascular disease (five cohorts; RR 1.6, 1.1-2.4; sensitivity 8%, 2-26; specificity 93%, 86-97); and increased cardiovascular mortality (four cohorts; hazard ratio [HR] 1.7, 95% CI 1.1-2.5) and all-cause mortality (HR 1.6, 1.1-2.3). A difference of 10 mm Hg or higher was associated with peripheral vascular disease (five studies; RR 2.4, 1.5-3.9; sensitivity 32%, 23-41; specificity 91%, 86-94). INTERPRETATION: A difference in SBP of 10 mm Hg or more, or of 15 mm Hg or more, between arms might help to identify patients who need further vascular assessment. A difference of 15 mm Hg or more could be a useful indicator of risk of vascular disease and death. FUNDING: Royal College of General Practitioners, South West GP Trust, and Peninsula Collaboration for Leadership in Applied Health Research and Care. PMID- 22293370 TI - Possible involvement of S-nitrosylation of brain cyclooxygenase-1 in bombesin induced central activation of adrenomedullary outflow in rats. AB - We previously reported that both nitric oxide (NO) generated from NO synthase by bombesin and NO generated from SIN-1 (NO donor) activate the brain cyclooxygenase (COX) (COX-1 for bombesin), thereby eliciting the secretion of both catecholamines (CA) from the adrenal medulla by brain thromboxane A(2)-mediated mechanisms in rats. NO exerts its effects via not only soluble guanylate cyclase, but also protein S-nitrosylation, covalent modification of a protein cysteine thiol. In this study, we clarified the central mechanisms involved in the bombesin-induced elevation of plasma CA with regard to the relationship between NO and COX-1 using anesthetized rats. Bombesin (1 nmol/animal, i.c.v.)-induced elevation of plasma CA was attenuated by carboxy-PTIO (NO scavenger) (0.5 and 2.5 MUmol/animal, i.c.v.), but was not influenced by ODQ (soluble guanylate cyclase inhibitor) (100 and 300 nmol/animal, i.c.v.). The bombesin-induced response was effectively reduced by dithiothreitol (thiol-reducing reagent) (0.4 and 1.9 MUmol/kg/animal, i.c.v.) and by N-ethylmaleimide (thiol-alkylating reagent) (0.5 and 2.4 MUmol/kg/animal, i.c.v.). The doses of dithiothreitol also reduced the SIN-1 (1.2 MUmol/animal, i.c.v.)-induced elevation of plasma CA, but had no effect on the U-46619 (thromboxane A(2) analog) (100 nmol/animal, i.c.v.)-induced elevation of plasma CA even at higher doses (1.9 and 9.7 MUmol/kg/animal, i.c.v.). Immunohistochemical studies demonstrated that the bombesin increased S nitroso-cysteine-positive cells co-localized with COX-1 in the spinally projecting neurons of the hypothalamic paraventricular nucleus (PVN). Taken together, endogenous NO seems to mediate centrally administered bombesin-induced activation of adrenomedullary outflow at least in part by S-nitrosylation of COX 1 in the spinally projecting PVN neurons in rats. PMID- 22293371 TI - Drug-induced activation of the nervous control of inflammation: a novel possibility for the treatment of hypoxic damage. AB - Together with undernutrition and, on the opposite, overeating and obesity, sudden tissue hypoperfusion is the most important cause of mortality and disability worldwide. Tissue hypoperfusion/hypoxia rapidly triggers an unrestrained inflammatory cascade that is the main responsible for the severity of the eventual outcome. The brain plays a key role in inflammation, either through activation of the hypothalamic-pituitary-adrenal humoral response or through activation of the vagal "cholinergic anti-inflammatory pathway". Both humoral and nervous brain responses to inflammation are under the regulatory control of melanocortins, which have moreover a direct anti-inflammatory effect on inflammatory cells. Abundant experimental and clinical evidence indicates that MC(3)/MC(4) melanocortin receptor agonists and cholinergic receptor agonists (mainly at the alpha7-nicotinic subtype) should by now be considered as completely innovative, effective drugs for the treatment of hypoxic conditions; melanocortin agonists being practically devoid of harmful side effects. PMID- 22293372 TI - Hard end points are needed for intensive glycaemic control in patients with type 2 diabetes. PMID- 22293374 TI - Lifestyle intervention in preschool children has little effect on obesity. PMID- 22293376 TI - Hypotension is more risky than hypertension in very old people. PMID- 22293377 TI - DNA methylation may be associated with health inequalities. PMID- 22293378 TI - Evidence supports the need to offer treatment as part of shared decision making. PMID- 22293379 TI - Does the BMJ have a particular ideology to pursue in assisted dying? PMID- 22293380 TI - Type 2 diabetes is a poor example of the overuse of surrogate markers. PMID- 22293381 TI - ABPI responds to article on concept of Pharmacare. PMID- 22293382 TI - Brave new post-iconoclastic world. PMID- 22293383 TI - Why not sell alcohol in alcohol units or metric units, not volume? PMID- 22293384 TI - Surrogate end points: studying their benefits, taxonomy, and semantics. PMID- 22293385 TI - NICE needs to move faster to keep up with NHS changes. PMID- 22293386 TI - Two tests may be better than one in bowel cancer screening, finds study. PMID- 22293387 TI - Minimally invasive osteotomy for symptomatic bunionette deformity is not advisable for severe deformities: a critical retrospective analysis of the results. AB - Bunionette, or tailor's bunion, is a painful protrusion on the plantar and/or lateral aspect of the fifth metatarsal head. Until recently, there have been very good results reported in literature when minimally invasive therapy is used to treat this deformity. In this study, the authors critically review the outcome of patients operated by the minimal invasive technique. A total of 31 feet were retrospectively reviewed with a mean follow-up of 52 months (range 14-106 months). The results were related to the preoperative severity of the bunionette deformity. The mean intermetatarsal angle IV/V was reduced from 12 degrees to 7.5 degrees postoperatively. The American Orthopaedic Foot and Ankle Society score showed good and excellent values (80-100 points) at follow-up in 16 (12 type I, 4 type III) feet. Fourteen (2 type I, 5 type II, 7 type III) feet were rated as satisfactory (60-80 points) and one (type III) foot with fair (56 points). Nine patients (5 type II and 4 type III) indicated that they would not undergo the operative procedure again. Our results show inclusive evidence that minimal invasive osteotomies have a good clinical outcome in the treatment of high-grade deformities. The best future option is to consider the classification of the deformity before a minimally invasive operation is to take place. PMID- 22293388 TI - Minimally invasive flexor hallucis longus transfer in management of acute achilles tendon rupture associated with tendinosis: a case report. AB - Chronic tendinopathy is characterized by pain in the tendon, generally at the start and completion of exercise. However, tendinosis may lead to decreased blood flow, increased stiffness of the tendon and reduced tensile strength, and predispose to rupture. Operative treatment is indicated to restore the function of the Achilles tendon and alleviate the prerupture heel cord pain. A case of acute Achilles tendon rupture with extensive tendinosis that was successfully treated with minimally invasive flexor hallucis longus transfer is reported. PMID- 22293389 TI - Revision of failed osteochondral autologous transplantation procedure for chronic talus osteochondral lesion with iliac crest graft and autologous matrix-induced chondrogenesis: a case report. AB - This article describes a novel technique for treatment of recurrent large osteochondral lesions of the talus using autologous matrix-induced chondrogenesis with a collagen I/III matrix. PMID- 22293390 TI - Lengthening z-osteotomy of the fibula to correct persistent talar shift following open reduction internal fixation of ankle fractures. AB - BACKGROUND: In cases where ankle fracture union has been compromised by persistent syndesmotic diastasis following open reduction internal fixation, both external rotation and shortening of the fibula have been identified as prominent features. OBJECTIVE: This study reports a technique that uses a z-osteotomy to achieve both lengthening and internal rotation of the fibula to correct persistent talar shift following ankle fracture fixation. METHODS: Four patients with persistent talar shift following open reduction internal fixation for an ankle fracture received z-osteotomy of the fibula to achieve both lengthening and internal rotation. RESULTS: At the latest clinic review, all 4 ankles exhibited satisfactory clinical and radiological union. All patients have returned to full mobility and are satisfied with the outcome. CONCLUSIONS: This study demonstrates the effectiveness of lengthening z-osteotomy of the fibula in correcting persistent talar shift following internal fixation of ankle fractures. LEVEL OF EVIDENCE: Therapeutic Level V. PMID- 22293391 TI - Dentirumai philippinensis n. gen., n. sp. (Nematoda: Philometridae), a new tissue infecting philometrid nematode from the loach goby Rhyacichthys aspro (Valenciennes) (Rhyacichthyidae) in the Philippines. AB - A new genus and species of the philometrid nematode Dentirumai philippinensis n. gen., n. sp. Philometrinae, Philometridae, are described on the basis of the female specimens found in the loach goby, Rhyacichthys aspro (Valenciennes), from the upper Bianuan River, Municipality of Casiguran, Aurora Province, in the Philippine Archipelago. Dentirumai philippinensis was collected from the body cavity, subcutaneous tissues near the bases of the pectoral and pelvic fins, and surrounding body tissues in the hypaxial musculature of R. aspro. Based on light microscopic and scanning electron microscopic examination, the new nematode species is morphologically close to the genus Rumai Travassos, 1960 except for one major difference, i.e. the presence of a sclerotized ring in the oral aperture armed with distinct numerous minute teeth on its inner surface. This important taxonomic feature makes it possible to erect a new genus, Dentirumai n. gen. to accommodate the newly discovered philometrid species. A key to genera of the Philometrinae is provided. PMID- 22293392 TI - Carbon nanotube/graphene nanocomposite as efficient counter electrodes in dye sensitized solar cells. AB - We demonstrated the replacement of the Pt catalyst normally used in the counter electrode of a dye-sensitized solar cell (DSSC) by a nanocomposite of dry spun carbon multi-walled nanotube (MWNT) sheets with graphene flakes (Gr-F). The effectiveness of this counter electrode on the reduction of the triiodide in the iodide/triiodide redox (I(-)/I(3)(-)) redox reaction was studied in parallel with the use of the dry spun carbon MWNT sheets alone and graphene flakes used independent of each other. This nanocomposite deposited onto fluorinated tin oxide-coated glass showed improved catalytic behavior and power conversion efficiency (7.55%) beyond the use of the MWNTs alone (6.62%) or graphene alone (4.65%) for the triiodide reduction reaction in DSSC. We also compare the use of the carbon MWNT/Gr-F composite counter electrode with a DSSC using the standard Pt counter electrode (8.8%). The details of increased performance of graphene/MWNT composite electrodes as studied are discussed in terms of increased catalytic activity permitted by sharp atomic edges that arise from the structure of graphene flakes or the defect sites in the carbon MWNT and increased electrical conductivity between the carbon MWNT bundles by the graphene flakes. PMID- 22293393 TI - Association between the catechol-O-methyltransferase (rs4680: Val158Met) polymorphism and serum alanine aminotransferase activity. AB - In our previous proteomic study in rat liver damaged by carbon tetrachloride, soluble catechol-O-methyltransferase (COMT) increased as a phosphorylated form and decreased as a dephosphorylated form. This finding raised the possibility that the COMT protein is associated with liver function. Thus, we hypothesized that (1) the COMT gene contributes to liver homeostasis and (2) a COMT polymorphism (rs4680: Val158Met) causing thermolability of enzymatic activity affects liver enzymes (e.g., aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (gamma-GT)) in serum. To investigate (2), we statistically analyzed the association between COMT genotypes and serum ALT activity in a cross-sectional study using data from the Japan Multi Institutional Collaborative Cohort (J-MICC) Study. We conducted a multiple logistic regression analysis for males (n=838) and females (n=970). Those participants having missing values or a past history of liver cirrhosis or liver cancer were excluded. ALT values were divided into two; elevated (30IU/L <=; males n=239, females n=90) and normal (<30IU/L; males n=599, females n=880). In females, non-adjusted and adjusted odds ratios for ALT values in the rs4680 A/A homozygote (n=126) compared with the wild-type G/G homozygote (n=397) were 0.37 (95% CI 0.14-0.96) and 0.34 (95% CI 0.13-0.93), respectively. In males, an analysis of the population aged 35-69 did not reveal any significant difference, but the population aged 45-54 had a significant difference in the non-adjusted and adjusted odds ratio in the G/A heterozygote (n=89) (0.50 (95% CI 0.27-0.92) and 0.35 (95% CI 0.18-0.71)) and in the A/A homozygote (n=22) (0.34 (95% CI 0.11 0.99) and 0.22 (95% CI 0.07-0.72)), compared with the G/G homozygote (n=88). These data suggest that the COMT polymorphism affects serum ALT activity to maintain liver function. PMID- 22293394 TI - Phospho-ibuprofen (MDC-917) suppresses breast cancer growth: an effect controlled by the thioredoxin system. AB - INTRODUCTION: We have recently synthesized phospho-ibuprofen (P-I; MDC-917), a safer derivative of ibuprofen, which has shown anti-cancer activity. We investigated its efficacy and mechanism of action in the treatment of breast cancer in preclinical models. METHODS: We evaluated the anti-breast-cancer efficacy of P-I alone or incorporated into liposomes (Lipo-P-I) in human estrogen receptor-positive (MCF-7) and triple-negative, i.e., estrogen receptor-negative, progesterone receptor-negative and HER2-negative (MDA-MB231) breast cancer cell lines - as they represent the most frequent (estrogen receptor-positive) and the most difficult-to-treat (triple-negative) subtypes of breast cancer - and their xenografts in nude mice. We assessed the effect of P-I on the levels of reactive oxygen nitrogen species in response to P-I using molecular probes, on the thioredoxin system (expression and redox status of thioredoxin-1 (Trx-1) and thioredoxin reductase activity), on cyclooxygenase 2, NF-kappaB and mitogen activated protein kinase cell signaling; and on the growth of xenografts with stably knocked-down Trx-1. RESULTS: Compared with controls, P-I 400 mg/kg/day inhibited the growth of MDA-MB231 xenografts by 266%, while the growth of MCF-7 xenografts was inhibited 51% byP-I 300 mg/kg/day and 181% by Lipo-P-I 300 mg/kg/day. In both cell lines, P-I induced oxidative stress and suppressed the thioredoxin system (oxidized Trx-1 and decreased its expression; inhibited thioredoxin reductase activity). These changes triggered downstream redox signaling: the activity of NF-kappaB was suppressed and the Trx-1-ASK1 complex was dissociated, activating the p38 and JNK mitogen-activated protein kinase cascades. Trx-1 knockdown abrogated the anti-cancer effect of P-I in vitro and in vivo. CONCLUSION: P-I is safe and effective against breast cancer. Liposomal formulation enhances its efficacy; the effect is heavily dependent on the induction of oxidative stress and the suppression of the thioredoxin system. P-I merits further evaluation as an agent for the treatment of breast cancer. PMID- 22293395 TI - HBV DNA level at 24 weeks is the best predictor of virological response to adefovir add-on therapy in patients with lamivudine resistance. AB - BACKGROUND: The aim of this study was to investigate the relationship between HBV DNA levels at baseline and on-treatment and the virological response at 96 weeks after adefovir add-on therapy in chronic hepatitis B (CHB) patients with lamivudine resistance. METHODS: Lamivudine and adefovir combination therapy was administered to 122 CHB patients for >24 months. RESULTS: Virological response (HBV DNA negativity) was achieved in 53 (43.3%) and 62 patients (50.8%) at 48 and 96 weeks, respectively. The receiver operating characteristic curve analysis showed that the HBV DNA level at week 24 had a greater power (area under the receiver operating characteristic curve 0.978; 95% CI 0.949, 1.000; P<0.001) to predict the virological response at week 96 of treatment than did the pre treatment HBV DNA level (area under the receiver operating characteristic curve 0.771; 95% CI 0.640, 0.902; P<0.001). The best cutoff value for the HBV DNA level, at week 24, for the prediction of the virological response at week 96 was 200 IU/ml (3 log(10) copies/ml), with a sensitivity and specificity of 90.3% and 95.0%, respectively. Using this time frame and cutoff value, 56 (90.3%) out of 62 patients that had a virological response at 96 weeks had <200 IU/ml HBV DNA at 24 weeks. CONCLUSIONS: Although the HBV DNA level at baseline is often used to predict the antiviral potency of lamivudine and adefovir combination treatment in CHB patients with lamivudine resistance, the results of this study suggest that the HBV DNA level at 24 weeks is a better marker for the virological response. PMID- 22293396 TI - Chemical shift prediction for protein structure calculation and quality assessment using an optimally parameterized force field. AB - The exquisite sensitivity of chemical shifts as reporters of structural information, and the ability to measure them routinely and accurately, gives great import to formulations that elucidate the structure-chemical-shift relationship. Here we present a new and highly accurate, precise, and robust formulation for the prediction of NMR chemical shifts from protein structures. Our approach, shAIC (shift prediction guided by Akaikes Information Criterion), capitalizes on mathematical ideas and an information-theoretic principle, to represent the functional form of the relationship between structure and chemical shift as a parsimonious sum of smooth analytical potentials which optimally takes into account short-, medium-, and long-range parameters in a nuclei-specific manner to capture potential chemical shift perturbations caused by distant nuclei. shAIC outperforms the state-of-the-art methods that use analytical formulations. Moreover, for structures derived by NMR or structures with novel folds, shAIC delivers better overall results; even when it is compared to sophisticated machine learning approaches. shAIC provides for a computationally lightweight implementation that is unimpeded by molecular size, making it an ideal for use as a force field. PMID- 22293398 TI - Disordered proteins studied by chemical shifts. PMID- 22293397 TI - In vivo magnetic resonance spectroscopy of GABA: a methodological review. PMID- 22293399 TI - Process and reaction monitoring by low-field NMR spectroscopy. PMID- 22293400 TI - Narrow safety range of intraoperative rectal irradiation exposure volume for avoiding bleeding after seed implant brachytherapy. AB - BACKGROUND & PURPOSE: Rectal toxicity is less common after 125I seed implant brachytherapy for prostate cancer, and intraoperative rectal dose-volume constraints (the constraint) is still undetermined in pioneering studies. As our constraint failed to prevent grade 2 or 3 rectal bleeding (bled-pts) in 5.1% of patients, we retrospectively explored another constraint for the prevention of rectal bleeding. MATERIALS AND METHODS: The study population consisted of 197 patients treated with the brachytherapy as monotherapy using real-time intraoperative transrectal ultrasound (US)-guided treatment at a prescribed dose of 145 Gy. Post-implant dosimetry was performed on Day 1 and Day 30 after implantation using computed tomography (CT) imaging. Rectal bleeding toxicity was classified by CTC-AE ver. 3.0 during a mean 29-month (range, 12-48 months) period after implantation. The differences in rV100s were compared among intraoperative, Day 1 and Day 30 dosimetry, and between that of patients with grade 2 or 3 rectal bleeding (the bled-pts) and of the others (the spared-pts). All patients were divided into groups based on provisional rV100s that were increased stepwise in 0.1-cc increments from 0 to 1.0 cc. The difference in the ratios of the bled-pts to the spared-pts was tested by chi-square tests, and their odds ratios were calculated (bled-OR). All statistical analyses were performed by t-tests. RESULTS: The mean values of rV100us, rV100CT_1, and rV100CT_30 were 0.31 +/- 0.43, 0.22 +/- 0.36, and 0.59 +/- 0.68 cc, respectively. These values temporarily decreased (p = 0.020) on Day 1 and increased (p = 0.000) on Day 30. There was no significant difference in rV100s between the bled-pts and spared-pts at any time of dosimetry. The maximum bled-OR was identified among patients with an rV100us value above 0.1 cc (p = 0.025; OR = 7.8; 95% CI, 1.4-145.8); an rV100CT_1 value above 0.3 cc (p = 0.014; OR = 16.2; 95% CI, 3.9-110.7), and an rV100CT_30 value above 0.5 cc (p = 0.019; OR = 6.3; 95% CI, 1.5-42.3). CONCLUSION: By retrospective analysis exploring rV100 as intraoperative rectal dose-volume thresholds in 125I seed implant brachytherapy for prostate cancer, it is proved that rV100 should be less than 0.1 cc for preventing rectal bleeding. PMID- 22293401 TI - A novel role for microglia in minimizing excitotoxicity. AB - Microglia are the abundant, resident myeloid cells of the central nervous system (CNS) that become rapidly activated in response to injury or inflammation. While most studies of microglia focus on this phenomenon, little is known about the function of 'resting' microglia, which possess fine, branching cellular processes. Biber and colleagues, in a recent paper in Journal of Neuroinflammation, report that ramified microglia can limit excitotoxicity, an important insight for understanding mechanisms that limit neuron death in CNS disease. PMID- 22293402 TI - Myb: getting involved in EMT. PMID- 22293403 TI - Letter from the publisher. PMID- 22293404 TI - Drosophila cyclin D/Cdk4 regulates mitochondrial biogenesis and aging and sensitizes animals to hypoxic stress. AB - Drosophila cyclinD (CycD) is the single fly ortholog of the mammalian cyclin D1 and promotes both cell cycle progression and cellular growth. However, little is known about how CycD promotes cell growth. We show here that CycD/Cdk4 hyperactivity leads to increased mitochondrial biogenesis (mitobiogenesis), mitochondrial mass, NRF-1 activity (Tfam transcript levels) and metabolic activity in Drosophila, whereas loss of CycD/Cdk4 activity has the opposite effects. Surprisingly, both CycD/Cdk4 addition and loss of function increase mitochondrial superoxide production and decrease lifespan, indicating that an imbalance in mitobiogenesis may lead to oxidative stress and aging. In addition, we provide multiple lines of evidence indicating that CycD/Cdk4 activity affects the hypoxic status of cells and sensitizes animals to hypoxia. Both mitochondrial and hypoxia-related effects can be detected at the global transcriptional level. We propose that mitobiogenesis and the hypoxic stress response have an antagonistic relationship, and that CycD/Cdk4 levels regulate mitobiogenesis contemporaneous to the cell cycle, such that only when cells are sufficiently oxygenated can they proliferate. PMID- 22293405 TI - Quality of life of myopic subjects with different methods of visual correction using the NEI RQL-42 questionnaire. AB - PURPOSE: To evaluate different aspects of the visual-related quality of life using the National Eye Institute Refractive Error Quality of Life (NEI RQL)-42 questionnaire in low and moderate myopic subjects corrected with different refractive treatments including laser-assisted in situ keratomileusis (LASIK), orthokeratology (OK), soft contact lenses (SCLs), and spectacles. METHODS: The NEI RQL-42 questionnaire was administered to 217 subjects at one single clinic. All the questions consisted of 13 different subscales that were analyzed separately. The results from subjects with -1.00 to -3.00 diopter myopia corrected with LASIK (n=41), OK (n=37), SCLs (n=44), or spectacles (n=45) were compared with each other and with emmetropic subjects (n=50). RESULTS: Statistically significant differences among all groups were found in all subscales, except for satisfaction with correction (P=0.135). The average decrease in quality of life compared with emmetropes were -7.1% (P=0.021) for LASIK, -13.0% (P<0.001) for OK, -15.8% (P<0.001) for spectacles, and -17.3% (P<0.001) for SCLs. CONCLUSIONS: Although all patients in each group were considered to be successfully visually corrected, quality of life related to vision was markedly different in certain NEI RQL-42 categories. LASIK showed the lowest average decrease in quality of vision compared with emmetropes. OK was comparable with LASIK in independence of visual correction, and SCL wear was superior to LASIK and OK lens wear in glare. Except for glare and diurnal fluctuations, contact lenses (SCL and OK) were comparable with or superior to spectacle correction. PMID- 22293406 TI - Interactions of ocular isolates of gram-negative bacteria with lactoferrin. AB - PURPOSE: The aim was to examine the interaction of lactoferrin with gram-negative bacteria isolated from ocular adverse responses. METHODS: Strains representing the species Pseudomonas aeruginosa (six strains), Aeromonas hydrophila, Escherichia coli, Stenotrophomonas maltophilia, and Haemophilus influenza were tested. A modified enzyme-linked immunosorbent assay was used to measure the binding of the strains to native and deglycosylated lactoferrin. The effect on the viability of strains was measured by incubating strains in media containing lactoferrin as the sole carbon and nitrogen source. Siderophore production by strains was measured using an established assay. RESULTS: All the strains except the single strain of E. coli (Ecol8) were capable of binding to lactoferrin. The ocular isolate of H. influenzae showed strong affinity for lactoferrin. The P. aeruginosa strains and the strain of S. maltophilia showed significantly reduced (80%-100% reduction; P<0.05) binding to lactoferrin that had been enzymatically deglycosylated, whereas deglycosylation had no effect on the binding of other strains/species tested. Most strains were able to grow and produce siderophores in the presence of lactoferrin as the sole carbon and nitrogen source. CONCLUSIONS: The ability to bind to and grow on lactoferrin can be important for gram-negative pathogens that colonize the ocular environment, because this could allow bacteria to survive and propagate in the presence of tear fluid. PMID- 22293407 TI - Thymoquinone ameliorates the immunological and histological changes induced by exposure to imidacloprid insecticide. AB - Previous studies have shown that thymoquinone (TQ) exerts protective effects in some models of pesticide-induced immunotoxicity. However, no data exist regarding its possible modulatory effect during imidacloprid (IC)-induced toxicity. Therefore, the aim of this study was to investigate the impact of TQ on IC induced immunotoxicity. Sixty adult male albino rats were divided into three groups of twenty animals each. The control group was given distilled water orally, while the IC-treated group was orally administered 0.01 LD(50 )(0.21 mg/kg body weight) of IC insecticide daily for 28 days. The animals in the third group (IC/TQ group) received the same IC dose as the IC-treated group for 28 days in addition to an intraperitoneal (I.P.) injection of TQ (1 mg/kg) once every 7 days. We found that IC induced significant increases (P < 0.05) in total leukocyte counts, total immunoglobulins (Igs) (especially IgGs), the hemagglutination of antibodies, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and malondialdehyde (MDA) compared to the control group. In contrast, significant decreases (P < 0.05) in phagocytic activity, chemokine expression and chemotaxis were observed in the IC treated group, as were severe histopathological lesions in the liver, spleen and thymus. Notably, TQ supplementation ameliorated the biochemical, histopathological, and immunological changes induced by IC by increasing phagocytic activity, chemokinesis, chemotaxis, immunoglobulin levels, and the hemagglutination of antibodies, as well as by decreasing hepatic enzymes and serum MDA levels. Taken together, our data reveal the benefits of TQ supplementation for ameliorating IC toxicity by decreasing oxidative stress and enhancing immune efficiency. PMID- 22293408 TI - 3,5-dibenzyloxy-4'-hydroxystilbene induces early caspase-9 activation during apoptosis in human K562 chronic myelogenous leukemia cells. AB - A series of 22 stilbene derivatives based on resveratrol were synthesized incorporating acetoxy-, benzyloxy-, carboxy-, chloro-, hydroxy- and methoxy functional groups. We examined the cytotoxicity of these 22 stilbenes in human K562 chronic myelogenous leukemia cells. Only four compounds were cytotoxic namely 4'-hydroxy-3-methoxystilbene (15), 3'-acetoxy-4-chlorostilbene (19), 4' hydroxy-3,5-dimethoxystilbene or pterostilbene (3) and 3,5-dibenzyloxy-4' hydroxystilbene (28) with IC(50)s of 78 uM, 38 uM, 67 uM and 19.5 uM respectively. Further apoptosis assessment on the most potent compound, 28, confirmed that the cells underwent apoptosis based on phosphatidylserine externalization and loss of mitochondrial membrane potential. Importantly, we observed a concentration-dependent activation of caspase-9 as early as 2 hr with resultant caspase-3 cleavage in 28-induced apoptosis. Additionally, a structure activity relationship (SAR) study proposed a possible mechanism of action for compound 28. Taken together, our data suggests that the pro-apoptotic effects of 28 involve the intrinsic mitochondrial pathway characterized by an early activation of caspase-9. PMID- 22293409 TI - Bcl-xL and Mcl-1 are involved in prevention of in vitro apoptosis in rat late stage erythroblasts derived from bone marrow. AB - Apoptosis controls erythroid homeostasis by balancing survival and death of erythroid cells. The mitochondrial pathway of apoptosis involves regulation of apoptotic events caused by the Bcl-2 family proteins, including the anti apoptotic and pro-apoptotic members. However, little has been reported on the role of the anti-apoptotic Bcl-2 family members in rat late-stage erythroblasts that are no longer erythropoietin (EPO)-dependent. In the present study, to investigate this we analyzed changes in apoptosis-related factors that occurred in vitro. EPO stimulation resulted in reduced apoptotic cell death of the late stage erythroblasts accompanied by decreased caspase-3 and caspase-9 activities, which is indicative of the induction of apoptosis through the mitochondrial pathway. Analysis of mRNA expression of the Bcl-2 family proteins demonstrated that EPO stimulation up-regulated the Bcl-xL mRNA, resulting in decreases in the mRNA ratios of Bak, Bax, and Bad to Bcl-xL. Also, the mRNA ratios of Bak and Noxa to Mcl-1 were decreased, mainly due to up-regulation of Mcl-1 mRNA. These results showed a close association between reduced apoptotic cell death and increased mRNA levels of Bcl-xL and Mcl-1 in the presence of EPO. Thus, the present study suggests that Bcl-xL may be an important anti-apoptotic factor of rat late-stage erythroblasts as has been reported in murine erythroblasts. Moreover, the results also indicate the possibility that Mcl-1 may act on the rat late-stage erythroblasts as an anti-apoptotic factor. PMID- 22293410 TI - Metabolism of di (2-ethylhexyl) phthalate (DEHP): comparative study in juvenile and fetal marmosets and rats. AB - We compared the metabolic profile of di (2-ethylhexyl) phthalate (DEHP) in juveniles and fetus between rats and marmosets. STUDY-I: (14)C-DEHP (100 and 2,500 mg/kg) was singly administered to juvenile and adult marmosets by gavage. C(max) of the radioactivity in juvenile marmosets was 6.45 and 31 ug eq./g, respectively. The radioactivity excreted mainly into feces; however, at least 10% of the radioactivity was absorbed even at 2,500 mg/kg. No abnormal accumulation was observed in the male reproductive organs. STUDY-II: (14)C-DEHP (100 mg/kg) was singly administered to juveniles of rat and marmoset. The plasma radioactivity in marmosets was about 5% to 9% of that in rats. Free forms of mono 2-ethylhexyl phthalate (MEHP) and its oxidized metabolites such as oxo-, OH-, and COOH-MEHP were detected as the main compositions in rat plasma. In marmosets, free form of MEHP was also detected as a major composition, but not for oxidized MEHP metabolites. In rats, oxidized MEHP metabolites were excreted into urine as unconjugated forms. MEHP and its oxidized metabolites were also detected in marmoset urine; however, they were mostly glucuronized. No specific accumulation of the radioactivity was noted in the testes of either species; however, the radioactivity concentration in the marmoset testes was much lower than that in rats. STUDY-III: (14)C-DEHP (100 mg/kg) was singly administered to dams on gestation day 130 for marmosets and day 20 for rats. In either species, no specific accumulation of radioactivity was noted in the testis of fetuses from the dams treated with (14)C-DEHP; however, the radioactivity in the rat testis was about 20-times higher than that in the marmoset. Major metabolite components in rat whole fetal tissue were free forms of MEHP, OH-MEHP, and oxo-MEHP. Free form of MEHP was also detected as only a peak in the marmoset fetal tissue. PMID- 22293411 TI - An unusual phenotypic and genotypic expression in F2 generation following one stage zidovudine exposure during pregnancy and lactation- an experiment in mice. AB - Zidovudine (3'-Azido-2', 3'-dideoxythymidine, AZT, ZDV) is routinely used as one of the component of antiretroviral therapy to prevent transmission of the HIV infection from mother to child. The drug, when given during pregnancy can give rise to myriad toxicities as reported in previous studies on human, animal and in vitro experiments. The present study was an attempt to explore the Zidovudine teratogenesis in F1 and F2 generation of mice following initial maternal exposure to Zidovudine during pregnancy, through delivery and lactation. The F1 generation actually would have got the exposure during embryonic development and infant stages. Pregnant Swiss mice were treated orally with ZDV 50 mg/kg/day or distilled water (control), from day eighth of gestation, through delivery and continued for first ten days of lactation. The F1 generation litters were raised and mated to produce F2 generation mice. An interesting phenotype of "healthy" and "sick" was noted in F2 generation but not in the F1 generation. In F2 generation 35% died on different postnatal day during 120 days of follow up period. Chromosomal study from bone marrow of F1 and F2 showed various chromosomal aberrations. Lipodystrophy and hepatotoxicity was observed in "sick" mice. The study generated a hypothesis of recessive mutation and concludes that Zidovudine is a transplacental genotoxic agent. The result of present study therefore suggests the need to study the effect of zidovudine in human subjects for a longer period of time to rule out similar genotoxic effect. PMID- 22293412 TI - Repeated dose and reproductive/developmental toxicity of perfluorooctadecanoic acid in rats. AB - Male and female rats were given perfluorooctadecanoic acid (PFOdA) by gavage at 40, 200 or 1,000 mg/kg/day, and each female was mated with a male in the same dose group after 14-day administration. Males were dosed for 42 days and females were dosed throughout the gestation period until day 5 of lactation. One female given 1,000 mg/kg/day was euthanized on day 18 of gestation due to a moribund condition; however, no other treatment-related clinical signs of toxicity were observed. Body weights fell at 1,000 mg/kg/day from day 28 through the administration period in males and throughout gestation and lactation in females. Red blood cell count, hemoglobin level and hematocrit were decreased at 200 and 1,000 mg/kg/day in males and activated partial thromboplastin time was prolonged at 1,000 mg/kg/ day in females. Histopathological examination revealed hepatic changes, such as centrilobular hypertrophy and necrosis, in males given 200 and 1,000 mg/kg/day and in females given 1,000 mg/kg/day. Pancreatic zymogen granule was decreased in both sexes at 1,000 mg/kg/day. As for reproductive and developmental toxicity, there were decreases in the number of corpora lutea, implantation, total number of pups born and the number of live pups on postnatal days 0 and 4 at 1,000 mg/kg/day. At this dose, birth weights of pups were decreased and postnatal body weight gain was inhibited. Based on these findings, the NOAEL of PFOdA was considered to be 40 mg/kg/day for repeated dose toxicity and 200 mg/kg/day for reproductive/developmental toxicity. PMID- 22293413 TI - Teratogenicity of multi-wall carbon nanotube (MWCNT) in ICR mice. AB - A possible teratogenicity of multi-wall carbon nanotube (MWCNT) was assessed using ICR mice. MWCNTs were suspended in 2% carboxymethyl cellulose and given intraperitoneally or intra-tracheally to pregnant ICR mice on day 9 of the gestation. All fetuses were removed from the uterus on day 18 of the gestation, and were examined for external and skeletal anomalies. In the intraperitoneal study, various types of malformation were observed in all MWCNT-treated groups (2, 3, 4 and 5 mg/kg body weight, intraperitoneal). In contrast, such malformations were observed in groups given 4 or 5 mg/kg body weight, but not in that treated with 3 mg/kg in the intratracheal study. In either study, the number of litters having fetuses with external malformation and that of litters having fetuses with skeletal malformations were both increased in proportion to the doses of MWCNT. The present results are the first to report that MWCNT possesses the teratogenicity at least under the present experimental conditions. Mechanism(s) to result such malformations is yet unclear and further experiment is necessary. PMID- 22293414 TI - A repeated dose 90-day oral toxicity study of cyflumetofen,a novel acaricide, in rats. AB - Cyflumetofen is a novel acaricide which is highly active against phytophagous mites. As a part of safety assessment, a repeated dose 90-day oral toxicity study of cyflumetofen was conducted in Fischer (F344/DuCrj) rats of both sexes. Technical grade cyflumetofen was administered in feed to groups of 10 males and 10 females at dose levels of 0, 100, 300, 1,000, and 3,000 ppm. Prothrombin time was prolonged in males at 3,000 ppm and plasma globulin levels were decreased in females at 1,000 and 3,000 ppm. At necropsy, enlarged and whitish adrenals were observed in females at 3,000 ppm. There were statistically significant increases in relative liver weight (ratio to body weight) in males and relative adrenal weight in females in the 1,000 ppm group; increased relative liver and kidney weights in both sexes at 3,000 ppm, and increased absolute and relative weights of adrenals in females at 3,000 ppm. Increased absolute liver weight was also noted in males at 3,000 ppm. Histopathologically, at 1,000 and 3,000 ppm males had diffuse vacuolation and females had diffuse hypertrophy of adrenal cortical cells. In addition, vacuolation of ovarian interstitial gland cells was noted in females at 1,000 and 3,000 ppm. There were no treatment-related changes in any parameters for either sex in other dose groups. Based on these results, the no observed-adverse-effect level (NOAEL) of cyflumetofen was judged to be 300 ppm for both sexes (16.5 mg/kg/day for males and 19.0 mg/kg/day for females). PMID- 22293415 TI - Cattle bile but not bear bile or pig bile induces lipid profile changes and fatty liver injury in mice: mediation by cholic acid. AB - Three types of animal bile preparation, bear bile (BB), cattle bile (CB) and pig bile (PB) differ in bile acid composition and are supposed to exert different pharmacotoxicological actions. Dietary supplementation with CB at 1% (w/w) for 4 weeks decreased triacylglycerol (TAG) level but increased total cholesterol (CHO) level in serum, which were associated with fatty liver injury in mice. The increased levels of cholesterol esters (CE) and monounsaturated fatty acids (MUFA) in the serum and liver were observed in the mice fed the CB-supplemented diet. Lipid abnormalities and fatty liver injury observed in the mice fed the CB diet were not induced by the supplementation with BB and PB. The supplementation with cholic acid (CA), the most abundant bile acid in CB, could induce lipid abnormalities and fatty liver injury, which were indistinguishable from those induced by CB supplementation. CB and CA supplementation induced similar changes in the expression levels of mRNAs in the liver. Thus, CB induced lipid abnormalities and fatty liver injury, which can be attributed to the actions of CA contained in CB. The inabilities of BB and PB to induce lipid abnormalities and fatty liver injury are supposed to be due to their limited contents of CA. PMID- 22293416 TI - Hair-to-blood ratio and biological half-life of mercury: experimental study of methylmercury exposure through fish consumption in humans. AB - The hair-to-blood ratio and biological half-life of methylmercury in a one compartment model seem to differ between past and recent studies. To reevaluate them, 27 healthy volunteers were exposed to methylmercury at the provisional tolerable weekly intake (3.4 ug/kg body weight/week) for adults through fish consumption for 14 weeks, followed by a 15-week washout period after the cessation of exposure. Blood was collected every 1 or 2 weeks, and hair was cut every 4 weeks. Total mercury (T-Hg) concentrations were analyzed in blood and hair. The T-Hg levels of blood and hair changed with time (p < 0.001). The mean concentrations increased from 6.7 ng/g at week 0 to 26.9 ng/g at week 14 in blood, and from 2.3 to 8.8 ug/g in hair. The mean hair-to-blood ratio after the adjustment for the time lag from blood to hair was 344 +/- 54 (S.D.) for the entire period. The half-lives of T-Hg were calculated from raw data to be 94 +/- 23 days for blood and 102 +/- 31 days for hair, but the half-lives recalculated after subtracting the background levels from the raw data were 57 +/- 18 and 64 +/- 22 days, respectively. In conclusion, the hair-to-blood ratio of methylmercury, based on past studies, appears to be underestimated in light of recent studies. The crude half-life may be preferred rather than the recalculated one because of the practicability and uncertainties of the background level, though the latter half-life may approximate the conventional one. PMID- 22293417 TI - Changes of ghrelin and leptin levels in plasma by cigarette smoke in rats. AB - Cigarettes smoke (CS) limits food intake and body weight increase. Ghrelin and leptin are hormones regulating appetite and energy balance. While ghrelin increases food intake and causes a positive energy balance, leptin decreases food intake and enhances a negative energy balance. To investigate the possible role of ghrelin and leptin regarding the negative energy balance caused by CS, 10-week old male Wistar rats (n = 10) were exposed to CS from 30 cigarettes twice a day for 5 days a week for four weeks. In the smoking group, food intake and body weight gain were less than those in the non-smoking group (n = 10) during the entire CS exposure. In the smoking group, the plasma levels of acyl ghrelin were significantly higher (75.9 +/- 5.1 fmol/ml versus 46.5 +/- 3.3 fmol/ml, p < 0.01), while those of leptin were significantly lower than those in the non smoking group (434.9 +/- 41.1 ng/ml versus 744.0 +/- 45.4 ng/ml, p < 0.01) after the final CS exposure. However, the plasma des-acyl ghrelin levels were not affected by CS exposure. These results suggested that acyl ghrelin and leptin levels in plasma may change to compensate for the negative energy balance by CS. PMID- 22293418 TI - Protective effect of sulphoraphane against oxidative stress mediated toxicity induced by CuO nanoparticles in mouse embryonic fibroblasts BALB 3T3. AB - Despite the great interest in nanoparticles (NPs) safety, no comprehensive test paradigm has been developed. Oxidative stress has been implicated as an explanation behind the toxicity of NPs. It is reported that sulphoraphane (SFN) present in cruciferous vegetables like cauliflower and broccoli has potential to protect cells from oxidative damage and inflammation. However, protective role of SFN in nanotoxicity is not explored. We investigated the protective effect of SFN against the toxic response of copper oxide (CuO) NPs in mouse embryonic fibroblasts (BALB 3T3). Results showed that CuO NPs induced dose-dependent (5-15 ug/ml) cytotoxicity in BALB 3T3 cells demonstrated by MTT and lactate dehydrogenase (LDH) assays. CuO NPs were also found to induce oxidative stress in dose-dependent manner indicated by induction of reactive oxygen species (ROS) and lipid peroxidation (LPO) and depletion of glutathione and glutathione reductase. Co-treatment of BALB 3T3 cells with SFN (6 uM) significantly attenuated the cytotoxicity, ROS generation and oxidative stress caused by CuO NPs. Moreover, we found that co-treatment of another antioxidant N-acetyl-cysteine (NAC) (2 mM) also significantly attenuated glutathione depletion caused by CuO NPs but protection from the loss of cell viability due to CuO NPs exposure was not significant. We believe this is the first report showing that SFN significantly protected the BALB 3T3 cells from CuO NPs toxicity, which is mediated through generation of oxidants and depletion of antioxidants. Consequently, protective mechanism of SFN against CuO NPs toxicity was different from NAC that should be further investigated. PMID- 22293419 TI - Health effects of low-level cadmium intake and the role of metallothionein on cadmium transport from mother rats to fetus. AB - Female Wistar rats were given Cd (as CdCl(2)) at a dose of 0, 1, 2, and 5 mgCd/kg/day by gastric tube daily for 6 consecutive days each week for 10 weeks. After the birth, newborn rats were sacrificed on day 1 and at 4 weeks. Mother rats were sacrificed after 4 weeks of lactation The concentrations of Cd in uterus and placenta, and metallothionein (MT) in the uterus of mother rats were determined. The concentrations of Cd in kidney and liver of newborn rats were also determined. Expression of iso-MT genes (I, II, and III) in the uterus of mother rats was measured using RT-PCR. The Cd concentration in the liver of newborn rats at the first day after birth was higher than in the kidney, while the concentration in the kidney of newborn rats at the fourth week after the birth was significantly higher than in the liver. The uterine MT concentration increased with accumulation of Cd; however, the MT concentration did not increase enough to prevent Cd transport to the fetus. On the other hand, it was considered that more Cd was transported as the chemical form of nonMT-Cd from mother rat, and accumulated in the liver rather than kidney of the fetus. Based on analyses of the Cd distribution in the liver and kidney of newborn rats, we speculate that MT in the uterus and placenta does not play a significant role in preventing Cd transport through the placenta from the uterus to the fetus. PMID- 22293420 TI - SNP-induced apoptosis may be mediated with caspase inhibitor by JNK signaling pathways in rabbit articular chondrocytes. AB - NO plays an important role in cartilage destruction by inducing apoptosis of chondrocytes. Here we investigated the role of c-Jun N-terminal kinase (JNK) signal transduction pathways in the apoptosis induced by NO donor sodium nitroprusside (SNP) in rabbit articular chondrocytes. We used Annexin V-FITC/PI flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) assay to detect apoptosis rate. The expressions of p38, NF-kappaB p65, caspase-3 and p53 genes at protein levels were measured by Western blotting assay. RT-PCR was performed to show the mRNA expression of caspase-3, and the activity of caspase-3 was also detected. To investigate the effect of JNK-specific inhibitor SP600125, chondrocytes were pretreated with SP600125 ahead of SNP treatment. Treatment with SNP accelerated apoptosis in a concentration dependent manner, while such acceleration was reduced by SP600125 pretreatment. Moreover, we found that SP600125 significantly decreased NO-induced NF-kappaB, p53, caspase-3 protein expressions and caspase-3 mRNA expression, as well as intracellular caspase-3 activity (P < 0.05). Collectively, these data suggest that JNK plays an important role through stimulating NF-kappaB, p53 and caspase-3 activation. PMID- 22293421 TI - Metallothionein (MT) 1/2 expression in MT 1/2 and MT 3 knock-out mice and Long Evans Cinnamon (LEC) rats. AB - Metallothionein (MT) is known to be involved in various physiological roles and diseases. However, a standard method for MT measurement has not been established until recently. Therefore, we have developed an easy and specific enzyme-linked immunosorbent assays (ELISA) to determine MT-1 and MT-2. In order to evaluate the method we developed, MT-1/2 in liver, kidney and brain was determined in wild type (WT), MT-1/2 knockout (KO) and MT-3 KO mice, with and without Cd treatment. MT 1/2 in urine was determined in genetically disordered LEC rats (an animal model of Wilson disease). MT-1/2 concentrations in the liver, kidney and brain in MT-1/2 KO mice were significantly lower compared to those of WT and MT-3 KO mice. MT-1/2 concentrations in the livers of WT mice significantly increased with Cd administration, but not in MT-1/2 KO mice. Similar results were observed by immunohistochemical staining. To confirm the molecular weight (MW) of MT detected in organs by the ELISA, analysis with a Sephadex G-75 was performed. Two peaks of MT-1/2 (MW small and large) were detected in WT and MT-3 KO mice. The small MT peak was mostly depleted in MT 1/2-KO mice, while a large MT peak remained. A significant increase in MT-1/2 concentration was detected in the urine of LEC rats with age and especially at the hepatitis stage. In conclusion, MT-1/2 ELISA and immunohistochemical staining was highly correlated with MT-1/2 determination in experimental animal specimens and could be a robust analytical tool for physiological and toxicological studies. PMID- 22293422 TI - Effects of sustained stimulation with multi-wall carbon nanotubes on immune and inflammatory responses in mice. AB - Possible effects of multi-wall carbon nanotubes (MWCNTs) on immune and inflammatory responses were examined in mice. Female ICR mice were given a single intraperitoneal administration (2 mg/kg body weight) of either MWCNTs, carbon black (CB), or crocidolite (blue asbestos) and controls received a vehicle of 2% sodium carboxymethyl cellulose (CMC Na). In the peritoneal cavity of MWCNT administered mice, the liver had changed to a rounded shape and fibrous adhesions were seen on internal organs. Peritoneal cells overexpressed mRNA for genes of T helper (Th)2 cytokines (interleukin [IL]-4, IL-5, and IL-13), Th17 cytokine (IL 17), pro-inflammatory cytokines/chemokines (IL-1beta, IL-33, tumor necrosis factor alpha, and monocyte chemotactic protein-1), and myeloid differentiation factor 88 for at least 2 weeks after the administration of MWCNTs, while those of Th1 cytokine genes (IL-2 and interferon gamma) were overexpressed several weeks later and expression levels remained high up to 20 weeks. In MWCNT-treated mice, the numbers of leukocytes, monocytes, and granulocytes in the peripheral blood and the expression of the leukocyte adhesion molecules, cluster of differentiation (CD)49d and CD54, on granulocytes were increased 1 week after administration and remained high up to week 20. Production of ovalbumin-specific IgM and IgG(1) was enhanced by MWCNTs. These changes were not observed after CB or crocidolite administration. Thus, this study showed that MWCNTs exhibited sustained stimulating effects on immune and inflammatory responses, unlike the other mineral fibers with structural similarities. PMID- 22293423 TI - Diurnal variation of cadmium-induced mortality in mice. AB - Circadian timing largely modifies efficacy of many medicinal drugs. This viewpoint has been applied in the clinical medicine, known as chronotherapy. We think this viewpoint should also be introduced into toxicology as "chronotoxicology", however, information about the diurnal variation in toxicant sensitivity is still very scarce. We present here a clear and reproducible diurnal variation of cadmium (Cd)-induced mortality in mice. Male ICR mice kept under standard condition (12 hr light/dark cycle, lights on at 08:00) were injected with CdCl(2) (7.2 mg/kg, one shot) intraperitoneally at different time points in the day (zeitgeber time (ZT) 0, 4, 8, 12, 16 or 20). Survival number was determined at 14 days after injection. Interestingly, mice were sensitive to Cd acute toxicity at ZT8, while tolerant at mid-dark to early-light phase (ZT16, ZT20 and ZT0). Hepatic GSH level showed small daily fluctuation, lowest at ZT8 and highest at ZT20, and this fluctuation was similar to the diurnal variation of Cd sensitivity. In contrast, hepatic metallothionein (MT) level was not significant in these time points, although their level also showed small daily fluctuation. Our results indicated that Cd-induced mortality had clear diurnal variation, and suggested that the hepatic GSH level was one of the important factors for determination of this Cd-induced diurnal mortality. PMID- 22293424 TI - Useful method for evaluation of local irritation using auricular subcutis of rabbits. AB - For the local irritation caused by Doxorubicin hydrochloride (DXR) which have leaked to the subcutis from the vein, the usefulness of the model using the auricular subcutis of rabbits was examined. DXR was administered to the subcutis in the ear auricle, abdominal region and dorsal region, and the local irritation reactions induced were evaluated according to the Draize criteria, by comparison of the damaged area and by the histopathological method. Macroscopic formations of erythema, edema and eschar were observed in the auricular subcutis, but there were no changes in the abdominal or dorsal subcutis. Histopathological examination showed changes such as edema, hemorrhage and necrosis at all administration sites and the changes were most severe in the auricular subcutis among the 3 regions. The reactions in the ear auricle observed were closest to the skin damage noted in humans by administration of DXR. In order to find out why the degree of local damage is different in these 3 regions, Evans blue was administered to these regions to compare its diffusibility in these regions. The diffusibility of Evans blue was lowest in the ear auricle. It is estimated that the difference in the local damage induced by DXR in these regions might be due to the difference in the retention time of DXR in the subcutis. Therefore, the evaluation for local irritation using the auricular subcutis model in rabbits is considered to be useful for estimation of skin damage caused by leakage of DXR to the subcutis. PMID- 22293425 TI - Effects of restricted feeding on fetal and placental development in pregnant rabbits. AB - In our previous study on the effects of restricted feeding on pregnant rabbits (Matsuoka et al., 2009), animals given 20 g/day of diet on and after gestation day 6 (GD 6) showed significant changes in blood coagulation-related parameters suggesting a tendency to bleed and a decrease in serum concentration of progesterone, an important factor to maintain pregnancy, on GD 22, and a half of them showed serum progesterone concentrations less than 4.0 ng/ml which resulted in abortions on and after GD 23. In the present study, the effects of restricted feeding of 20 g/day from GD 6 to GD 22 on embryo-fetal and placental development on GD 23 as well as on blood coagulation-related parameters and serum progesterone concentrations on GD 22 were examined in pregnant rabbits. As compared with the non-restricted feeding (Not-treated, NT) group, the restricted feeding (RF) group showed lower values of platelets, fibrinogen, activated partial thromboplastin time (APTT) and antithrombin III (ATIII) and a longer prothrombin time (PT), reflecting an inhibition of blood coagulation, and a decrease in serum progesterone concentration on GD 22. Cesarean section performed on GD 23 revealed that the RF group showed a tendency towards an increase in the embryo-fetal death index and lower body weights and placental volumes compared with the NT group. Histological examination of the placenta in the RF group revealed that the labyrinth zone was thin and many glycogen-containing cells still remained in the basal zone, suggesting a delay in placental growth. PMID- 22293426 TI - Protein array profiling of mouse serum, six months post whole body radiation with (56)Fe. AB - To determine the chronic effects of heavy ion irradiation, an antibody based proteomic microarray technology was applied to monitor alterations in the serum proteome, six months after whole body irradiation of adult male C57Bl/6 mice with 0.5 Gray of (56)Fe. Out of 507 proteins, irradiation reduced expression of 25 proteins and enhanced expression of 12 proteins in serum (> 5% change relative to sham-irradiated controls). Of the 25 proteins found to be down-regulated, Poly ADP Ribose Polymerase (PARP) was 13% lower in the 0.5Gy mice and among the up regulated proteins, beta-Tubulin was found to be 10% higher in the 0.5Gy group compared to the sham-irradiated 0Gy controls. Thus, irradiation with a relatively low dose of heavy ions caused persistent and selective changes in serum levels of proteins that are typically intracellular, suggesting chronic genotoxic damage. PMID- 22293427 TI - DNA microarray analysis of transcriptional responses of rats housed on solid and grid cage flooring. AB - We performed DNA microarray analysis on the white blood cells (WBCs) of rats housed on solid and grid cage flooring. The expression levels of 50 genes were found to increase more than 2-fold in the WBCs on grid cage flooring, including many genes encoding proteins involved in inflammatory or immune responses. It is therefore suggested that the health and welfare of laboratory rats is likely to be improved by housing rats on solid floors. PMID- 22293428 TI - Evidence that the north-south gradient of multiple sclerosis may not have disappeared. PMID- 22293429 TI - Sensitive detection assays for influenza RNA do not reveal viremia in US blood donors. AB - BACKGROUND: There have been anecdotal reports of influenza viremia since the 1960s. We present an assessment of the prevalence of seasonal and 2009 H1N1 influenza viremia (via RNA testing) in blood donor populations using multiple sensitive detection assays. METHODS: Several influenza RNA amplification assays, including transcription-mediated amplification (TMA) and 2 reverse-transcription polymerase chain reaction (RT-PCR) assays, were evaluated and used to test donor samples. Retrospective samples from 478 subjects drawn at sites with high influenza activity were tested. Prospective samples were collected from 1004 blood donors who called their donation center within 3 days of donation complaining of influenza-like illness (ILI). The plasma collected on the day of donation for these subjects was tested. RESULTS: Of the repository samples, 2 of 478 plasma samples were initially reactive but not repeat reactive by influenza TMA. Of blood donors reporting ILI symptoms postdonation, 1 of 1004 samples was TMA initially reactive but not repeat reactive; all samples were nonreactive by RT-PCR testing. CONCLUSIONS: Targeting blood donor populations most likely to have influenza infection, we failed to detect influenza RNA in 1482 donor samples, with most tested by 3 different RNA assays. Seasonal influenza does not appear to pose a significant contamination threat to the blood supply. PMID- 22293430 TI - How can the blood transfusion medicine community contribute to public health in tough economic times? PMID- 22293431 TI - Spontaneous clearance of chronic hepatitis C virus infection is associated with appearance of neutralizing antibodies and reversal of T-cell exhaustion. AB - BACKGROUND: Hepatitis C virus (HCV) readily establishes chronic infection with exhaustion of HCV-specific T cells and escape from neutralizing antibodies. Spontaneous recovery from chronic infection is rare and has never to our knowledge been studied immunologically. METHODS: We prospectively studied, from prior to infection through >2 years of follow-up, cytokines, HCV-specific T cells, and antibodies, as well as viral sequence evolution in a white male who spontaneously cleared HCV genotype 1a after 65 weeks. RESULTS: Significant alanine aminotransferase and plasma cytokine elevation and broad HCV-specific T cell responses did not result in HCV clearance in the acute phase. Frequency and effector function of HCV-specific T cells decreased thereafter, and HCV titers stabilized as is typical for the chronic phase. HCV clearance after 65 weeks followed the appearance of neutralizing antibodies at week 48 and was associated with reversal of HCV-specific T-cell exhaustion, as evidenced by reduced programmed death-1 (PD-1) expression and improved T-cell function. Clearance occurred without inflammation or superinfection with hepatitis B virus, human cytomegalovirus virus, influenza, and Epstein-Barr virus. CONCLUSIONS: T-cell exhaustion is reversible at least in the first 2 years of chronic HCV infection, and this reversion in conjunction with neutralizing antibodies may clear HCV. These findings are relevant for immunotherapy of chronic infections. PMID- 22293432 TI - Genetic diversity of recently acquired and prevalent HIV, hepatitis B virus, and hepatitis C virus infections in US blood donors. AB - BACKGROUND: Genetic variations of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) can affect diagnostic assays and therapeutic interventions. Recent changes in prevalence of subtypes/genotypes and drug/immune-escape variants were characterized by comparing recently infected vs more remotely infected blood donors. METHODS: Infected donors were identified among approximately 34 million US blood donations, 2006-2009; incident infections were defined as having no or low antiviral antibody titers. Viral genomes were partially sequenced. RESULTS: Of 321 HIV strains (50% incident), 2.5% were non-B HIV subtypes. Protease and reverse transcriptase (RT) inhibitor resistance mutations were found in 2% and 11% of infected donors, respectively. Subtypes in 278 HCV strains (31% incident) yielded 1a>1b>3a>2b>2a>4a>6d, 6e: higher frequencies of 3a in incident cases vs higher frequencies of 1b in prevalent cases were found (P = .04). Twenty subgenotypes among 193 HBV strains (26% incident) yielded higher frequencies of A2 in incident cases and higher frequencies of A1, B2, and B4 in prevalent cases (P = .007). No HBV drug resistance mutations were detected. Six percent of incident vs 26% of prevalent HBV contained antibody neutralization escape mutations (P = .01). CONCLUSIONS: Viral genetic variant distribution in blood donors was similar to that seen in high-risk US populations. Blood-borne viruses detected through large-scale routine screening of blood donors can complement molecular surveillance studies of highly exposed populations. PMID- 22293434 TI - A possible role of the dipole moment of the catalyst droplet in nanotube growth, alignment, chirality, and characteristics. AB - Why vapor species land on the surface of the nanoparticle seed for nanotube synthesis is a vital question. An investigation has been carried out to find an answer to it. For this, a model of the dipole moment has been developed. A bimetallic alloy (non-alloy, solid solution) exhibiting the shape of a cap has been assumed to function as the nanoparticle seed. Various features of the dipole moment have been examined. The influence of the dipole moment on nanotube synthesis, alignment, chirality, and characteristics has also been studied. Available experiments on the synthesis of carbon nanotubes employing bimetallic catalysts have been compared with the results from calculations. Close correspondence between the two demonstrates that the catalysts may exhibit a dipole moment and have a crucial role in nanotube synthesis and characteristics. The dipole moment has also been employed to determine why some nanotubes grow vertically, while others are bent. Calculated results appear to explain the basic causes for this. These results suggest that the electric field resulting from the dipole moment of catalysts may be important for the vertical alignment of nanotubes. They may attest to the validity of the model and to the existence of a dipole moment in seeds. Although considered for nanotube syntheses, the results may be applicable to other nanomaterials (nanotubes, nanowires, nanodots). PMID- 22293433 TI - Response of adipose tissue to early infection with Trypanosoma cruzi (Brazil strain). AB - Brown adipose tissue (BAT) and white adipose tissue (WAT) and adipocytes are targets of Trypanosoma cruzi infection. Adipose tissue obtained from CD-1 mice 15 days after infection, an early stage of infection revealed a high parasite load. There was a significant increase in macrophages in infected adipose tissue and a reduction in lipid accumulation, adipocyte size, and fat mass and increased expression of lipolytic enzymes. Infection increased levels of Toll-like receptor (TLR) 4 and TLR9 and in the expression of components of the mitogen-activated protein kinase pathway. Protein and messenger RNA (mRNA) levels of peroxisome proliferator-activated receptor gamma were increased in WAT, whereas protein and mRNA levels of adiponectin were significantly reduced in BAT and WAT. The mRNA levels of cytokines, chemokines, and their receptors were increased. Nuclear Factor Kappa B levels were increased in BAT, whereas Ikappakappa-gamma levels increased in WAT. Adipose tissue is an early target of T. cruzi infection. PMID- 22293435 TI - Multiplex PCR-based Alu insertion polymorphisms genotyping for identifying individuals of Japanese ethnicity. AB - Discrimination of Alu insertions is a useful tool for geographic ancestry analysis, and is usually performed by Alu element amplification and agarose gel electrophoresis. Here, we have developed a new fluorescence-based method for multiple Alu genotyping in forensic identification. Allele frequencies were determined in 70 Japanese individuals, and we selected 30 polymorphic Alu insertions. Three primers were designed for each Alu locus to discriminate alleles using the 3-6 bp differences in amplicon sizes. Furthermore, we classified the amplification primers for the 30 loci into three different sets, and PCR using each set of primers provided 10 loci fragments ranging from 50 to 137 bp. Based on population data, the probability of incorrectly assigning a match was 3.7*10(-13). Three independent amplifications and subsequent capillary electrophoresis enabled the sensitive genotyping of small amounts of DNA, indicating that this method is suitable for identifying individuals of Japanese ethnicity. PMID- 22293436 TI - Mortality of HIV-infected patients with or without cancer: comparison with the general population in Italy. AB - BACKGROUND: HAART has reduced mortality in HIV-infected patients; however, the risk of non-AIDS-related events has increased, including cancer. We compared mortality in HIV-infected patients with or without cancer with the general population in Italy. METHODS: Eligible patients were recorded in the San Raffaele Infectious Diseases Department database. The ratio of observed deaths to expected all-cause deaths (standardized mortality ratio [SMR]) was standardized for age and gender, and stratified by cancer occurrence or year of HIV infection (<=1998 or >1998). Expected all-cause deaths were obtained from the Istituto Superiore di Sanita (Rome, Italy; 2002 data). RESULTS: Among 6,495 HIV-infected patients, contributing 75,171 person-years, the SMR was 6.0 (95% CI 5.7, 6.4); SMRs decreased as age increased. Mortality rates were significantly higher than the general population for patients with or without cancer (SMR=15.1 [95% CI 13.6, 16.7] and 4.8 [95% CI 4.5, 5.1], respectively). For patients with or without cancer, SMRs were higher in those aged <45 years than older patients. SMRs for patients with cancer were almost stable in those infected with HIV <=1998 (15.3; 95% CI 13.7, 17.0) or >1998 (13.5; 95% CI 9.2, 19.1). Among patients with cancer diagnosed with HIV >1998, age-adjusted SMRs ranged from 216.0 (95% CI 43.4, 631.3) to 6.8 (95% CI 4.7, 9.7) in patients <30 years or >=70 years, respectively. CONCLUSIONS: Mortality in HIV-infected patients remains higher than the general population in Italy, with marked differences according to age, and cancer contributing to an increased excess of mortality. PMID- 22293437 TI - Impaired recruitment of neuroprotective microglia and T cells during acute neuronal injury coincides with increased neuronal vulnerability in an amyotrophic lateral sclerosis model. AB - Non-cell-autonomous motor neuronal death is suggested in a mutant Cu/Zn superoxide dismutase 1 (mSOD1)-mediated amyotrophic lateral sclerosis (ALS) model, in which microglia and T cells play significant roles in disease progression. However, it remains unknown whether these cells are toxic or protective. The present study aimed to clarify the developmental age-related alterations of neuronal, glial and T cell responses to acute neuron injury in non transgenic (N-Tg) mice, and the in vivo effects of mSOD1 on these changes by studying N-Tg and mSOD1-Tg mice subjected to unilateral hypoglossal nerve axotomy at young (8 weeks) and adult (17 weeks) ages. Adult N-Tg mice showed increased neuronal viability on day 21 after axotomy and trends toward increased numbers of recruited microglia on day 3 and T cells on day 7, in the hypoglossal nucleus, compared with young N-Tg mice. Quantitative comparisons between mSOD1-Tg and N-Tg mice at the same ages, on day 3 after axotomy, showed that microglial recruitment was significantly lower in mSOD1-Tg mice than in 17-week-old N-Tg mice (the disease progression stage), but the same difference was not seen in 8-week-old mice (the presymptomatic stage), despite good preservation of hypoglossal neurons. Infiltration of CD3-positive T cells, mostly CD4-positive, on day 7 and the viability rate of hypoglossal neurons on the operated side compared with the contralateral side on day 21 were significantly decreased in mSOD1-Tg mice compared with N-Tg mice aged 17 weeks, but the same difference was not seen in mice aged 8 weeks. On day 3 after axotomy, expression levels of IGF-1 mRNA in the operated hypoglossal nucleus were significantly lower in mSOD1-Tg mice than N-Tg mice at 17 weeks of age. The observation that depressed microglial and T cell responses and expression of neurotrophic factors coincided with reduced neuronal viability in adult mSOD1-Tg mice suggests that diminished neuroprotective functions of mSOD1 microglia and T cells may contribute to exaggerated neuronal death. PMID- 22293438 TI - Cochlear implant electrode array misplacement: a cautionary case report. AB - OBJECTIVE: To report a series of pitfalls and complications in a case of cochlear implantation. METHOD: Case report. RESULTS: An 11-year-old boy affected by auditory neuropathy underwent cochlear implantation. Intra-operative assessment was apparently consistent with correct insertion of the electrode array into the cochlea. However, subsequent high resolution computed tomography revealed that the entire electrode array was curled up within the vestibule. Revision surgery was complicated by cerebrospinal fluid leakage. A straight probe was repeatedly inserted into the internal auditory canal, before conversion to a canal wall down procedure and appropriate positioning of the electrode array. CONCLUSION: In this case, mild anteriorisation of the facial nerve created an awkward insertion angle for the electrode array via the retro-facial route, which may have triggered the described series of adverse events. PMID- 22293439 TI - Sequencing three crocodilian genomes to illuminate the evolution of archosaurs and amniotes. AB - The International Crocodilian Genomes Working Group (ICGWG) will sequence and assemble the American alligator (Alligator mississippiensis), saltwater crocodile (Crocodylus porosus) and Indian gharial (Gavialis gangeticus) genomes. The status of these projects and our planned analyses are described. PMID- 22293440 TI - Development and comparison of a real-time PCR assay for detection of Dichelobacter nodosus with culturing and conventional PCR: harmonisation between three laboratories. AB - BACKGROUND: Ovine footrot is a contagious disease with worldwide occurrence in sheep. The main causative agent is the fastidious bacterium Dichelobacter nodosus. In Scandinavia, footrot was first diagnosed in Sweden in 2004 and later also in Norway and Denmark. Clinical examination of sheep feet is fundamental to diagnosis of footrot, but D. nodosus should also be detected to confirm the diagnosis. PCR-based detection using conventional PCR has been used at our institutes, but the method was laborious and there was a need for a faster, easier-to-interpret method. The aim of this study was to develop a TaqMan-based real-time PCR assay for detection of D. nodosus and to compare its performance with culturing and conventional PCR. METHODS: A D. nodosus-specific TaqMan based real-time PCR assay targeting the 16S rRNA gene was designed. The inclusivity and exclusivity (specificity) of the assay was tested using 55 bacterial and two fungal strains. To evaluate the sensitivity and harmonisation of results between different laboratories, aliquots of a single DNA preparation were analysed at three Scandinavian laboratories. The developed real-time PCR assay was compared to culturing by analysing 126 samples, and to a conventional PCR method by analysing 224 samples. A selection of PCR-products was cloned and sequenced in order to verify that they had been identified correctly. RESULTS: The developed assay had a detection limit of 3.9 fg of D. nodosus genomic DNA. This result was obtained at all three laboratories and corresponds to approximately three copies of the D. nodosus genome per reaction. The assay showed 100% inclusivity and 100% exclusivity for the strains tested. The real-time PCR assay found 54.8% more positive samples than by culturing and 8% more than conventional PCR. CONCLUSIONS: The developed real-time PCR assay has good specificity and sensitivity for detection of D. nodosus, and the results are easy to interpret. The method is less time-consuming than either culturing or conventional PCR. PMID- 22293441 TI - The Strengths and Difficulties Questionnaire hyperactivity-inattention subscale is more sensitive for the ADHD-combined subtype than other subtypes in 7-9-year old school children. PMID- 22293442 TI - The Strongest Families intervention is more effective than usual care in children with mild or moderate oppositional, attention or anxiety disorders. PMID- 22293443 TI - Short-course Combivir after single-dose nevirapine reduces but does not eliminate the emergence of nevirapine resistance in women. AB - BACKGROUND: In the Treatment Options Preservation Study (TOPS) trial, 4 or 7 days of Combivir (CBV; zidovudine/lamivudine) with maternal single-dose nevirapine (sdNVP) significantly reduced the emergence of NVP resistance as determined by virus population genotyping. To detect NVP resistance with greater sensitivity, we analysed TOPS samples by allele-specific real-time PCR (ASP). METHODS: In a random subset of women from each arm of the trial, plasma samples from before and 6 weeks after sdNVP were analysed using ASP at codons 103, 181, 184 and 190. RESULTS: Samples were analysed from 27 women in the sdNVP arm and 24 each in the CBV 4-day (sdNVP/CBV4) and 7-day (sdNVP/CBV7) arms. ASP detected NVP-resistant variants in week 6 samples from 70% of women in the sdNVP arm, 29% in the sdNVP/CBV4 arm and 33% in sdNVP/CBV7 arm (P<0.01 for sdNVP/CBV4 or sdNVP/CBV7 versus sdNVP; P=1.0 for sdNVP/CBV4 versus sdNVP/CBV7). Lamivudine resistance was detected by ASP in only 1 of 51 women who received CBV. CONCLUSIONS: Short-course CBV significantly reduced but did not eliminate the emergence of NVP resistance after sdNVP. NVP-resistant variants were detected in about one-third of women despite CBV treatment, but the duration of persistence and clinical impact of these variants in response to antiretroviral therapy is uncertain. PMID- 22293444 TI - Corosolic acid ameliorates atherosclerosis in apolipoprotein E-deficient mice by regulating the nuclear factor-kappaB signaling pathway and inhibiting monocyte chemoattractant protein-1 expression. AB - BACKGROUND: Corosolic acid (CRA) is a pentacyclic triterpene acid that has been shown to exhibit an anti-atherosclerotic effect when added to diets of low density lipoprotein-deficient mice, but the mechanisms are unclear. The purpose of the present study was to investigate the molecular mechanisms by which CRA ameliorates atherosclerosis. METHODS AND RESULTS: The anti-atherosclerosis effect of CRA in apolipoprotein E-deficient mice fed a Western-type diet was evaluated using atherosclerosis lesion area, serum profiles, gene expression and histological lesions. In vitro, the mechanisms responsible for the anti inflammatory effect of CRA were investigated on a lipopolysaccharide-induced inflammation model. This model was also used to investigate in detail the effects of CRA on gene expression and nuclear factor (NF)-kappaB activation. Compared with the control group, the CRA-treated group exhibited a significant decrease in atherosclerotic lesion area, as well as expression of monocyte chemoattractant protein-1 (MCP-1) and CCR2. In vitro studies showed that CRA treatment downregulated the mRNA levels of MCP-1, and inhibited monocyte adhesion and migration, together with suppression of NF-kappaB signaling pathway. CONCLUSIONS: CRA is capable of ameliorating atherosclerosis in apolipoprotein E-deficient mice by, partly at least, inhibition of NF-kappaB activity along with decreased MCP-1 expression. PMID- 22293445 TI - Hypoxic preconditioning enhances angiogenic potential of bone marrow cells with aging-related functional impairment. AB - BACKGROUND: Hypoxic preconditioning of bone marrow cells (BMCs) from young healthy individuals can enhance the cells' therapeutic potential. Considering that the response to hypoxia may differ according to the quality of the cells, we assessed the effect of hypoxic preconditioning on BMCs from aged mice and compared the difference in response between BMCs from aged and young mice. METHODS AND RESULTS: BMCs from young (3 months) and aged (20-22 months) mice were subjected to hypoxic preconditioning by culture for 24 h in 2% O2. Compared with BMCs from young mice, those from aged mice showed significantly fewer CD34- or c kit-positive stem cells, higher expression of p53, and lower telomerase activity. Adhesion, survival and angiogenic potency were also lower in BMCs from aged mice, indicating an aging-related impairment. Hypoxia-preconditioned BMCs from aged mice showed enhanced adhesion, survival, and angiogenic potency with the in vitro assessments, as well as the in vivo implantation into ischemic hindlimbs. All the enhancements by hypoxic preconditioning were comparable between BMCs from aged and young mice, although the angiogenic potential of BMCs with and without hypoxic preconditioning was lower in old mice compared with young mice. CONCLUSIONS: Similar responses to hypoxia by BMCs from both aged and young mice suggest that hypoxic preconditioning could be a useful method of enhancing the angiogenic potential of BMCs. PMID- 22293446 TI - Coronary slow flow--prevalence and clinical correlations. AB - BACKGROUND: Coronary slow flow phenomenon (CSFP) is defined as delayed coronary opacification in the absence of obstructive coronary artery disease. In the present study, we sought to define its prevalence and clinical features. METHODS AND RESULTS: The 1,741 consecutive patients who underwent coronary angiography (CAG) were identified. Those with normal left ventricular ejection fraction and normal coronary arteries were included in the study (n=158). TIMI frame counts were calculated, and data on demographics, comorbidities, and medication use were collected. CSFP was defined as frame count > 27. Multivariate logistic regression analysis was used to identify independent predictors of CSFP. CSFP was identified in 96 (5.5%) subjects referred for CAG. Subjects with CSFP were more obese (body mass index [BMI] 33.9 vs. 29.8 kg/m2, P=0.003) and had lower high-density lipoprotein levels (39.7 vs. 45.7 mg/dl, P=0.04). In the CSFP group, total cholesterol, low-density lipoprotein and frame counts increased significantly with increasing vessel involvement (1-, vs. 2-, vs. 3-vessel involvement; P<0.05 for each variable). By multivariate analysis, male sex (odds ratio 3.36, 95% confidence interval 1.17-8.61, P=0.02) and higher BMI independently predicted the presence of CSFP (odds ratio 1.09, 95% confidence interval 1.03-1.15, P=0.003). CONCLUSIONS: CSFP is associated with male sex and obesity. Multivessel involvement may be a marker of more severe, diffuse disease. Further studies are needed to investigate this hypothesis. PMID- 22293447 TI - Prevalence and signal characteristics of late gadolinium enhancement on contrast enhanced magnetic resonance imaging in patients with takotsubo cardiomyopathy. AB - BACKGROUND: To determine the prevalence and signal intensity (SI) characteristics of late gadolinium enhancement (LGE) on magnetic resonance imaging (MRI) in takotsubo cardiomyopathy (TC). METHODS AND RESULTS: Cine, black-blood T2-weighted and LGE MR images were acquired in 23 patients with TC within 72 h of onset. Wall motion abnormality (WMA), edema and LGE were evaluated with a 16-segment model. The SI characteristics of LGE were analyzed using SI distribution in remote normal segments as reference. Follow-up MRI was performed 3 months later. Retrospective analysis of LGE MRI was also performed in 10 patients with acute myocardial infarction (AMI) to compare the SI characteristics between TC and AMI. In acute phase, WMA and edema were observed in 236 (64%) and 205 (56%) of 368 segments. LGE was observed in 10 (2.7%) of 368 segments and in 5 (22%) of 23 patients. All LGE lesions in TC exhibited transmural enhancement. The contrast-to noise ratio (CNR) in TC was significantly lower than that of AMI (3.1+/-0.3 standard deviations (SD) vs. 6.1+/-1.2 SD, P<0.01), and CNR value of 4 was useful for distinguishing TC from AMI. Both LGE and WMA disappeared within 12 months. CONCLUSIONS: Grey myocardial signal on LGE MRI may be observed in patients with TC. However, the extent of LGE is substantially less than that of WMA and edema, and disappears within 12 months. PMID- 22293448 TI - Epidemiology of prehypertension and associated risk factors in urban adults from 33 communities in China--the CHPSNE study. AB - BACKGROUND: The Seventh Report of The Joint National Committee has recently introduced the prehypertension category of blood pressure (BP) status that needs monitoring and intervention. Little is known about the epidemiology of prehypertension in urban China, so this study aimed at estimating the prevalence of prehypertension and identifying risk factors in urban Chinese adults. METHODS AND RESULTS: Using a multistage cluster and random sampling method, a representative sample of 25,196 urban adults aged 18-74 years in northeast of China was selected from 2009 to 2010. The survey of BP and associated risk factors was carried out in 33 communities. Multiple logistic regression methods were used to identify risk factors for prehypertension. Overall, 40.5% of urban Chinese adults had prehypertension, with a prevalence of 47.7% and 33.6% in men and women, respectively. Multivariate logistic regression analysis revealed the risk factors of being overweight (adjusted odds ratio [aOR]=1.38, 95% confidence interval [CI]: 1.26-1.52), obesity (aOR=3.94, 95%CI: 2.99-5.20), central obesity (aOR=2.13, 95%CI: 1.96-2.32). Being female, and having a higher education level, higher family income and diet control were protective factors. CONCLUSIONS: Prehypertension is common among urban residents in China, and is associated with many risk factors. Comprehensive lifestyle modifications need to be taken to decrease the incidence of prehypertension and to prevent prehypertension progressing to hypertension and cardiovascular disease. PMID- 22293449 TI - Effects of autologous bone marrow mononuclear cells implantation in canine model of pulmonary hypertension. AB - BACKGROUND: We investigated the safety and feasibility of intratracheal administration of autologous bone marrow-derived mononuclear cells (ABM-MNCs) and observed the effects in a canine model of pulmonary hypertension (PH). METHODS AND RESULTS: The PH model was induced by intravenous injection of 3mg/kg dehydromonocrotaline (DMCT) via the right atrium. Two weeks after DMCT administration, the animals received 4 different treatments (n=10 in each group): (I) negative control group; (II): ABM-MNCs group; (III) PH group; (IV) PH+ABM MNCs group. Six weeks after injection of cells (107), the hemodynamic data were significantly improved in group IV compared with group III (P<0.05). The ratio of right ventricular weight to left ventricular plus septal weight was significantly decreased in group IV compared with group III (P<0.05). The mRNA levels of vascular endothelial growth factor, preproendothelin-1, interleukin-6 and tumor necrosis factor-alpha were significantly improved in group IV compared with group III (P<0.05). The immunofluorescence result showed that 6 weeks after administration ABM-MNCs could differentiate into pulmonary vascular endothelial cells. CONCLUSIONS: Six weeks after intratracheal administration, ABM-MNCs significantly improved the impairment caused by DMCT in a canine model of PH (ie, decreased pulmonary arteriolar narrowing, alveolar septum thickening and right ventricular hypertrophy, enhanced angiogenesis) and this provides a firm foundation for a clinical trial. PMID- 22293450 TI - Right atrial anatomical remodeling affects early outcomes of nonvalvular atrial fibrillation after radiofrequency ablation. AB - BACKGROUND: The impact of the right atrial (RA) anatomical remodeling on outcomes of atrial fibrillation (AF) after radiofrequency ablation (RFA) is unclear. METHODS AND RESULTS: Sixty-three patients (50 men, 57+/-10 years, 23 persistent AF [PeAF]) who underwent RFA for AF were enrolled. Both RA and left atrial (LA) volumes, measured with multidetector computed tomography, as well as echocardiographic parameters were compared between subjects with early (<3 months, n=13) or 1-year (n=19) recurrence after RFA and without recurrence. The RA volume index (RAVI) was larger (98+/-21 vs. 77+/-22 ml/m2) and PeAF was more common (62% vs. 30%) in the early recurrence group (P<0.05 for all), whereas the LA volume index (LAVI) was similar between the 2 groups (78+/-15 vs. 72+/-19 ml/m2, P=0.23). Notably, RAVI was the only independent predictor of early recurrence (for each 10 ml/m2 increase, OR: 1.650, 95%CI: 1.017-2.677, P=0.04). PeAF was the only independent predictor of 1-year recurrence after RFA (OR: 4.496, 95%CI: 1.110-18.211, P=0.04), whereas RAVI and LAVI were not. CONCLUSIONS: RA anatomical remodeling might affect the early recurrence of AF after RFA. However, the chronicity of AF, rather than RA and LA anatomical remodeling, is a determinant of 1-year recurrence of AF after RFA. PMID- 22293451 TI - Dabigatran in clinical practice for atrial fibrillation with special reference to activated partial thromboplastin time. AB - BACKGROUND: The distribution of activated partial thromboplastin time (APTT) in nonvalvular atrial fibrillation (NVAF) patients under dabigatran therapy remains to be clarified. METHODS AND RESULTS: The study population was 196 NVAF patients who were treated with dabigatran in 2011 (126 with 220 mg/day). The APTT values showed a wide distribution among the patients, especially in those with a reduced dose, who seemed to show a high value even in patients without contraindications. CONCLUSIONS: We found a wide distribution of APTT in NVAF patients under dabigatran treatment. High APTT might help screen for bleeding risks among patients under dabigatran, but requires future investigation. PMID- 22293452 TI - Acute hyperglycemia in patients with acute myocardial infarction. AB - Acute hyperglycemia is a common feature during the early phase after acute myocardial infarction (AMI), regardless of diabetes status. Numerous studies have demonstrated that patients with AMI and hyperglycemia on admission have high rates of mortality. It has been reported that there is a linear positive relation between admission blood glucose levels and mortality after AMI. However, recent studies showed that the relationship is U-shaped in patients with a history of diabetes. Diabetic patients with moderate hyperglycemia (glucose 9-11 mmol/L) had the lowest mortality and not only severe hyperglycemia (glucose >= 11 mmol/L) but also euglycemia (glucose < 7 mmol/L) was associated with higher mortality. Although it has been debated whether acute hyperglycemia is causally related to adverse outcomes after AMI or is simply an epiphenomenon of severely damaged myocardium, multiple physiological studies have demonstrated that hyperglycemia has a direct detrimental effect on ischemic myocardium through several mechanisms, including oxidative stress, inflammation, apoptosis, endothelial dysfunction, hypercoagulation, platelet aggregation and impairment of ischemic preconditioning. Current guidelines recommend the use of an insulin-based regimen to achieve and maintain glucose levels < 10.0 mmol/dl, and emphasize the avoidance of hypoglycemia. However, the optimal management goal of glucose levels for patients with acute hyperglycemia remains uncertain. Further studies are warranted into the appropriate management in patients with AMI and acute hyperglycemia. PMID- 22293453 TI - Platelet count as a prognostic marker in patients with acute coronary syndromes. PMID- 22293454 TI - Uric acid and atrial fibrillation - cause or other association? - . PMID- 22293455 TI - Intensive glucose lowering in cardiovascular risk management - unsolved questions - . PMID- 22293456 TI - Guidelines for clinical use of cardiac nuclear medicine (JCS 2010) - digest version - . PMID- 22293457 TI - Neuroprotective function for ramified microglia in hippocampal excitotoxicity. AB - BACKGROUND: Most of the known functions of microglia, including neurotoxic and neuroprotective properties, are attributed to morphologically-activated microglia. Resting, ramified microglia are suggested to primarily monitor their environment including synapses. Here, we show an active protective role of ramified microglia in excitotoxicity-induced neurodegeneration. METHODS: Mouse organotypic hippocampal slice cultures were treated with N-methyl-D-aspartic acid (NMDA) to induce excitotoxic neuronal cell death. This procedure was performed in slices containing resting microglia or slices that were chemically or genetically depleted of their endogenous microglia. RESULTS: Treatment of mouse organotypic hippocampal slice cultures with 10-50 MUM N-methyl-D-aspartic acid (NMDA) induced region-specific excitotoxic neuronal cell death with CA1 neurons being most vulnerable, whereas CA3 and DG neurons were affected less. Ablation of ramified microglia severely enhanced NMDA-induced neuronal cell death in the CA3 and DG region rendering them almost as sensitive as CA1 neurons. Replenishment of microglia-free slices with microglia restored the original resistance of CA3 and DG neurons towards NMDA. CONCLUSIONS: Our data strongly suggest that ramified microglia not only screen their microenvironment but additionally protect hippocampal neurons under pathological conditions. Morphological activation of ramified microglia is thus not required to influence neuronal survival. PMID- 22293458 TI - Aluminum nanoparticles for plasmon-improved coupling of light into silicon. AB - This paper investigates the improved photo-current response obtained by depositing Al nanoparticles on top of a Si diode. Well defined Al nanodiscs with a diameter and height of 100 nm are produced on the surface of a Si diode using electron-beam lithography, and the change in photo-current generation is characterized. A blue shift of the photo-current response is demonstrated, substantially improving the relation between gains and losses compared to what is typically observed in similar schemes using Ag nanoparticles. Enhanced photo current response is observed in diodes with Al particles on the surface at all wavelengths larger than ~465 nm, thereby minimizing the losses in the blue range usually reported with Ag nanoparticles on the surface. PMID- 22293460 TI - Longer InN phonon lifetimes in nanowires. AB - We present a Raman scattering study of the anharmonic phonon decay of the [Formula: see text], [Formula: see text] and E1(LO) phonons in InN nanowires over the 80-400 K temperature range. While the temperature-dependent anharmonic decay in the nanowires is similar to that found for bulk InN, the background contribution to the phonon lifetime is strongly reduced as a result of the improved crystalline quality. High-resolution measurements reveal a remarkably long lifetime of the [Formula: see text] mode. From the comparison between the [Formula: see text] frequencies measured in the nanowires with those of the thin film we obtain the deformation potentials for the [Formula: see text] mode. PMID- 22293459 TI - Stress appraisals and cellular aging: a key role for anticipatory threat in the relationship between psychological stress and telomere length. AB - Chronic psychological stress is a risk factor for multiple diseases of aging. Accelerated cellular aging as indexed by short telomere length has emerged as a potential common biological mechanism linking various forms of psychological stress and diseases of aging. Stress appraisals determine the degree and type of biological stress responses and altered stress appraisals may be a common psychological mechanism linking psychological stress and diseases of aging. However, no previous studies have examined the relationship between stress appraisals and telomere length. We exposed chronically stressed female caregivers and non-caregiving controls (N=50; M age=62.14+/-6.10) to a standardized acute laboratory stressor and measured their anticipatory and retrospective threat and challenge appraisals of the stressor. We hypothesized that threat and challenge appraisals would be associated with shorter and longer telomere length respectively, and that chronic caregiving stress would influence telomere length through altered stress appraisals. Higher anticipatory threat appraisals were associated with shorter age-adjusted telomere length (beta=-.32, p=.03), but challenge appraisals and retrospective threat appraisals showed no independent association with telomere length. Caregivers reported significantly higher anticipatory (beta=-.36, p=.006) and retrospective (beta=-.29, p=.03) threat appraisals than controls, but similar challenge appraisals. Although there was no significant main effect of caregiver status on telomere length, caregiving had a significant indirect effect on telomere length through anticipatory threat appraisals. Exaggerated anticipatory threat appraisals may be a common and modifiable psychological mechanism of psychological stress effects on cellular aging. PMID- 22293462 TI - Horizontal gene transfer confers fermentative metabolism in the respiratory deficient plant trypanosomatid Phytomonas serpens. AB - Among trypanosomatids, the genus Phytomonas is the only one specifically adapted to infect plants. These hosts provide a particular habitat with a plentiful supply of carbohydrates. Phytomonas sp. lacks a cytochrome-mediated respiratory chain and Krebs cycle, and ATP production relies predominantly on glycolysis. We have characterised the complete gene encoding a putative pyruvate/indolepyruvate decarboxylase (PDC/IPDC) (548 amino acids) of P. serpens, that displays high amino acid sequence similarity with phytobacteria and Leishmania enzymes. No orthologous PDC/IPDC genes were found in Trypanosoma cruzi or T. brucei. Conservation of the PDC/IPDC gene sequence was verified in 14 Phytomonas isolates. A phylogenetic analysis shows that Phytomonas protein is robustly monophyletic with Leishmania spp. and C. fasciculata enzymes. In the trees this clade appears as a sister group of indolepyruvate decarboxylases of gamma proteobacteria. This supports the proposition that a horizontal gene transfer event from a donor phytobacteria to a recipient ancestral trypanosome has occurred prior to the separation between Phytomonas, Leishmania and Crithidia. We have measured the PDC activity in P. serpens cell extracts. The enzyme has a Km value for pyruvate of 1.4mM. The acquisition of a PDC, a key enzyme in alcoholic fermentation, explains earlier observations that ethanol is one of the major end products of glucose catabolism under aerobic and anaerobic conditions. This represents an alternative and necessary route to reoxidise part of the NADH produced in the highly demanding glycolytic pathway and highlights the importance of this type of event in metabolic adaptation. PMID- 22293461 TI - Low rates of nucleoside reverse transcriptase inhibitor resistance in a well monitored cohort in South Africa on antiretroviral therapy. AB - BACKGROUND: The emergence of complex HIV-1 drug resistance mutations has been linked to the duration of time patients are on a failing antiretroviral drug regimen. This study reports on resistance profiles in a closely monitored subtype C infected cohort. METHODS: A total of 812 participants were enrolled into the CIPRA-SA 'safeguard the household' study, viral loads were determined at 12 weekly intervals for 96 weeks. Virological failure was defined as either a <1.5 log decrease in viral load at week 12 or two consecutive viral load measurements of >1,000 RNA copies/ml after week 24. Regimens prescribed were in line with the South African roll-out programme (stavudine, lamivudine, efavirenz or nevirapine). Viral RNA was extracted from patients with virological failure, and pol reverse-transcriptase PCR and sequence analysis were performed to determine drug-resistant mutations. RESULTS: Virological failure was observed in 83 participants on the first-line regimen during the study period, of which 61 (73%) had HIV-1 drug-resistant mutations. The M184V mutation was the most frequent (n=46; 65%), followed by K103N (46%) and Y181C (21%). Thymidine analogue mutations were infrequent (1%) and Q151M was not observed. CONCLUSIONS: Drug resistance profiles were less complex than has been previously reported in South Africa using the same antiretroviral drug regimens. These data suggest that frequent viral load monitoring limits the level and complexity of resistance observed in HIV-1 subtype C, preserving susceptibility to second-line options. PMID- 22293463 TI - Selection and emergence of pertussis toxin promoter ptxP3 allele in the evolution of Bordetella pertussis. AB - Evolutionary studies using single nucleotide polymorphisms (SNPs) have separated Bordetella pertussis isolates into six major clusters, with recent isolates forming cluster I. The expansion of cluster I isolates was characterised by changes in genes encoding antigenic components in acellular vaccines, including pertactin (Prn). Here, we determined the initial emergence of the pertussis toxin promoter allele, ptxP3, from an evolutionary perspective. This allele was previously shown in a study from the Netherlands to be associated with increased pertussis toxin production as a result of a single base mutation in the ptxP. The ptxP region of 313 worldwide isolates was sequenced, including 208 isolates from Australia collected over a 40 year period. Eight alleles were identified, of which only two predominated: ptxP1 and ptxP3. One novel allele was also found. ptxP3 was only found in SNP cluster I of B. pertussis and its emergence is concurrent with the change to the non-vaccine prn2 allele. Our results suggest that the globally distributed cluster I of B. pertussis has the ability to evade vaccine induced selection pressure. PMID- 22293464 TI - Diversity and phylogenetic analysis of endosymbiotic bacteria from field caught Bemisia tabaci from different locations of North India based on 16S rDNA library screening. AB - Bemisia tabaci is the major vector pest of agricultural crops all over the world. In this study we report the different bacterial endosymbionts associated with B. tabaci sampled from 14 different locations in North India. Using 16S rDNA clone library sequences we were able to identify Portiera, the primary endosymbiont of B. tabaci, and other secondary endosymbionts like Cardinium, Wolbachia, Rickettsia and Arsenophonus. Along with these we also detected Bacillus, Enterobacter, Paracoccus and Acinetobacter. These secondary endosymbionts were not uniformly distributed in all the locations. Phylogenetic analysis of 16S rDNA sequences of Cardinium, Wolbachia, Rickettsia and Arsenophonus showed that each of these bacteria form a separate cluster when compared to their respective counterparts from other parts of the world. MtCO1 gene based phylogenetic analysis showed the presence of Asia I and Asia II genetic groups of B. tabaci in N. India. The multiple correspondence analyses showed no correlation between the host genetic group and the endosymbiont diversity. These results suggest that the bacterial endosymbiont diversity of B. tabaci is much larger and complex than previously perceived and probably N. Indian strains of the bacterial symbionts could have evolved from some other ancestor. PMID- 22293465 TI - Detection of natural inter- and intra-genotype recombination events revealed by cap gene analysis and decreasing prevalence of PCV2 in wild boars. AB - Porcine circovirus type 2 (PCV2), the causative agent of a number of PCVAD (porcine circovirus associated diseases), is ubiquitous in domestic pig and wild boar populations. In the present study, using recombination detection program, phylogenetic analysis and base-by-base comparison of 28 PCV2 ORF2s (capsid protein coding gene) from wild boars and 8 from domestic pigs of Transylvania, recent natural intra- (PCV2b-1B/PCV2b-1C) and inter-genotype (PCV2a-2D/PCV2b-1C) recombination events were detected. Notably, one potential recombinant (F1-21) was detected in domestic pig with possible parental strains of wild boar origin. The estimated recombinant breakpoints comprised epitopes A, B and C of ORF2, without major changes in amino acid sequences. The prevalence of PCV2 in the wild boar population during the 5-year period following the first outbreaks of postweaning multisystemic wasting syndrome (PMWS) in domestic pigs in Romania showed a decrease from 13.4% to 8.3%. To our knowledge, this is the first study to show the existence of ORF2-based intra- and inter-genotype recombination in wild boar populations and the possible recombination between PCV2 strains of wild boars and domestic pigs. Our results suggest a certain independence of PCV2 infection in wild boar populations and demonstrate the possibility of infection with multiple PCV2 genotypes under natural circumstances. On the other hand, PCV2 genotypes specific for wild boars could be detected in domestic pig at lower frequency suggesting the possible spread of wild boar PCV2 to domestic swine. The recombination events described here may contribute to the genetic diversity of PCV2 and may also be the source of emergence of new PCV2 strains. PMID- 22293466 TI - Common inherited mitochondrial DNA mutations and nucleoside reverse transcriptase inhibitor-induced severe hyperlactataemia in HIV-infected adults: an exploratory study. AB - BACKGROUND: Genetic predisposition to dideoxynucleoside-induced mitochondrial dysfunction might be related to mitochondrial DNA (mtDNA) polymorphisms. Severe hyperlactataemia is probably the best model to assess such a predisposition. METHODS: For this exploratory study in White European and Black African HIV infected adults, hypervariable region 1 of mtDNA samples from peripheral blood mononuclear cells or buccal smears of patients who have developed confirmed severe hyperlactataemia was sequenced. Additionally, 21 single nucleotide polymorphisms and a 9 bp deletion were genotyped to assign mtDNA haplogroups. Finally, entire mtDNA sequencing was performed in a subset of European samples. Samples were obtained from Black African cases and controls recruited from a single centre in Johannesburg, South Africa and from white European cases from Amsterdam, London and Zurich. RESULTS: A total of 40 cases and 38 controls from Johannesburg were included. All of the cases and 33 controls were receiving stavudine-based therapy at the time of the index date (P=0.024). The distribution of mtDNA haplotypes was not different between cases and controls (P=0.137), and neither were the predicted haplogroups (P=0.751). In total, 11 of the 12 European cases were on stavudine and/or didanosine at the time of the event. No hypervariable region 1 haplotype was consistently found in the European cases. Sequencing of the entire mtDNA from three of these cases supported the absence of any shared mutations other than major alleles frequently seen in the mtDNA database. CONCLUSIONS: We did not find an association between homoplasmic inherited mtDNA polymorphisms and severe hyperlactataemia. Our data do not support the existence of non-synonymous mtDNA mutations that explain an increased predisposition to dideoxynucleoside-induced mitochondrial dysfunction. PMID- 22293467 TI - Three-dimensional characterization of pigment dispersion in dried paint films using focused ion beam-scanning electron microscopy. AB - The combination of integrated focused ion beam-scanning electron microscope (FIB SEM) serial sectioning and imaging techniques with image analysis provided quantitative characterization of three-dimensional (3D) pigment dispersion in dried paint films. The focused ion beam in a FIB-SEM dual beam system enables great control in slicing paints, and the sectioning process can be synchronized with SEM imaging providing high quality serial cross-section images for 3D reconstruction. Application of Euclidean distance map and ultimate eroded points image analysis methods can provide quantitative characterization of 3D particle distribution. It is concluded that 3D measurement of binder distribution in paints is effective to characterize the order of pigment dispersion in dried paint films. PMID- 22293468 TI - Influence of an autologous serum-supplemented medium on the proliferation and differentiation into neurons of canine bone marrow stromal cells. AB - We investigated the influence of autologous serum (AS)-supplemented medium on the proliferation and differentiation into neurons of canine bone marrow stromal cells (BMSCs). Canine BMSCs were cultured using alpha-MEM only, alpha-MEM with 10% fetal bovine serum (FBS), and 5, 10 and 20% AS-supplemented alpha-MEM. Growth of canine BMSCs was observed in all AS groups. The proliferation capacity of canine BMSCs in the AS groups was similar to that in the FBS group. No significant differences between the FBS and AS groups were observed in the percentage of the cells that changed to the neuron-like morphology and neuron specific enolase-positive ratio after neuronal differentiation. Canine BMSCs cultured using AS-supplemented medium were able to proliferate and showed neuronal differentiation potency. PMID- 22293469 TI - Lymphocyte blastogenic responses to food antigens in cats showing clinical symptoms of food hypersensitivity. AB - Three cats were diagnosed as having food hypersensitivity by food elimination and oral food provocation tests. Twelve allergenic food ingredients were identified by oral food provocation test in the 3 cats. Of the 12 food ingredients, 9 offending food antigens were shown to be positive in a lymphocyte stimulation test; however, none of them were positive in antigen-specific IgE testing, and only four food antigens were positive in intradermal testing. The stimulation indices in the lymphocyte stimulation tests for the 9 food ingredients were found to be decreased after the cats were fed elimination diets. The present study demonstrates that the lymphocyte stimulation test reflects an immunologic reaction involved in food hypersensitivity and can help identify allergenic food ingredients in feline food hypersensitivity. PMID- 22293470 TI - Pathological and immunohistochemical studies of subclinical infection of chicken anemia virus in 4-week-old chickens. AB - Subclinical infection of chicken anemia virus (CAV) at 4 to 6 weeks of age, after maternal antibodies have waned, is implicated in several field problems in broiler flocks. In order to understand the pathogenesis of subclinical infection with CAV, an immunopathological study of CAV-inoculated 4-week-old SPF chickens was performed. Sixty 4-week-old SPF chickens were equally divided into CAV and control groups. The CAV group was inoculated intramuscularly with the MSB1-TK5803 strain of CAV. Neither mortality nor anemia was detected in the CAV and control groups. In the CAV group, no signs were observed, except that some chickens were grossly smaller compared with the control group. Sporadic thymus lobes appeared to be reddening and atrophied. Within the first two weeks p.i. of CAV, there was a mild to moderate depletion of lymphocytes in the thymus cortex and spleen in some chickens. Moreover, lymphoid depletion of the bursa of Fabricius, proventriculus and cecal tonsils was observed. Hyperplastic lymphoid foci were observed in the liver, lungs, kidneys and heart at the 4th week p.i. of CAV. Immunohistochemically, a moderate lymphoid depletion of CD4(+)and CD8(+) T cells in the thymus cortex and spleen was observed in some chickens within two weeks p.i. of CAV. CAV inclusions and antigens were detected infrequently in the thymus cortex and spleen. It could be concluded that the immunosuppression in subclinical infection with CAV occurs as a result of reduction of cellular immunity. PMID- 22293471 TI - Psychosocial interventions for patients with chronic disease. AB - Treatment of patients with chronic diseases will be one of the main challenges of medicine in the future. This paper presents an overview of different origins, mechanism, and symptoms necessary for understanding new and different interventions that include a psychosomatic view.In a psychosomatic therapeutic intervention there are very different targets, such as psychological symptoms, personality traits, attitudes toward disease and life, risk behaviour, and social isolation and as biological targets the change of autonomic imbalance and of the effects of the psycho-endocrinological or psycho-immunological stress responses. And there are also different psychosomatic measures that influence the individual biological, psychological and sociological targets. There is a need to give different answer to different questions in the field of psychosomatic and behavioral medicine. Comparative effectiveness research is an important strategy for solving some methodological issues. What is the target of treatment for different diseases: Symptom reduction, healing, or limiting progression to the worst case - the death of patients. We know that, the patient-physician relationship is important for every medical/therapeutic action for patients with chronic diseases.This volume of BioPsychoSocial Medicine will present four different psychosomatic treatment studies from the clinical field in the sense of phase 2 studies: Reports of patients with obesity, anorexia nervosa, chronic somatoform pain and coronary artery disease were presented. PMID- 22293472 TI - Emerging roles of pulmonary macrophages in driving the development of severe asthma. AB - Asthma is recognized as a heterogeneous disorder, although in most patients, the clinical manifestations are effectively managed with established combination therapies. However, 5-10% of asthmatics have severe asthma, which does not respond to treatment, and these patients account for >50% of asthma-related healthcare costs. New investigations into the pathogenesis of glucocorticoid resistance in severe asthma indicate that pulmonary macrophages may play central roles in promoting airway inflammation, particularly in asthma that is resistant to steroid therapy. Importantly, factors that are linked to the activation of pulmonary macrophages may contribute to glucocorticoid resistance and severe asthma. Here, we review recent advances in understanding the roles of pulmonary macrophages in the mechanisms of glucocorticoid resistance and the pathogenesis of severe asthma. We discuss the role of macrophage phenotype, infection, IFN gamma, LPS, associated signaling pathways, TNF-alpha, MIF, and other macrophage associated factors. Understanding the pathogenesis of steroid-resistant severe asthma will contribute to the identification of optimal therapeutic strategies for the effective management of the disease. PMID- 22293473 TI - Comparative immunology, microbiology and infectious diseases. Introduction. PMID- 22293474 TI - Three-dimensional solution structure of bottromycin A2: a potent antibiotic active against methicillin-resistant Staphylococcus aureus and vancomycin resistant Enterococci. AB - The three-dimensional (3D) structure of bottromycin A(2), a natural anti methicillin-resistant Staphylococcus aureus (MRSA) and anti-vancomycin-resistant Enterococci (VRE) agent consisting of seven amino acids, has been investigated through NMR spectroscopy. On the basis of 57 experimental constraints, a total of 34 converged structures were obtained. The average pairwise atomic root mean square difference is 0.74+/-0.59 A for all heavy atoms. The resulting structure indicates an interesting feature in that the three C-terminal residues of bottromycin A(2) fold back on the 12-membered cyclic skeleton made by the four N terminal residues. Thus, MePro(2) and Thia-beta-Ala-OMe(7), modification of which significantly affects the antibacterial activities of bottromycin A(2), are located on one side of its 3D structure. These distinct structural features might be important for the binding of bottromycin A(2) with the bacterial ribosome. PMID- 22293475 TI - Development and evaluation of a monolithic floating drug delivery system for acyclovir. AB - Acyclovir (ACV), a model drug for this study, is one of the most effective drugs against viruses of the herpes group. Absorption of orally administered ACV is variable and incomplete, with a bioavailability of ca. 15-30%. The drug is absorbed in the duodenum after oral administration and hence, preparation of a floating drug delivery system (FDDS) for ACV may increase oral absorption of the drug. ACV matrix tablets (200 mg) containing an effervescent base (sodium bicarbonate and citric acid) and a binary combination of hydroxypropyl methylcellulose (HPMC) K4M with carbopol or sodium carboxymethyl cellulose (Na CMC) or polyvinylpyrrolidone (PVP) and/or sodium alginate were prepared by the direct compression method. The tablets were evaluated for physicochemical properties and in vitro floating ability (floating lag-time and duration), bioadhesiveness and drug release. The drug release studies were carried out in 0.1 N HCl (pH 1.2) at 37+/-0.5 degrees C. At appropriate time intervals, samples were withdrawn and assayed spectrophotometrically at lambda(max)=259 nm. The floating test showed tablets containing 15% effervescent base had a floating lag time of 10-30 s and a duration of floating time of 24 h. The formulations containing HPMC-PVP, HPMC-Na CMC, HPMC-carbopol, and HPMC-sodium alginate released about 60-90% of their drug content during a 12-h period. Increasing carbopol caused slower drug release. We concluded that the proposed tablets with 15% effervescent base, 20-30% HPMC, 30% Na CMC (and/or 20% PVP or 20% sodium alginate) showed good floating and drug release properties in vitro, and should be considered as FDDS for ACV. PMID- 22293476 TI - Acaricidal activity of DHEMH, derived from patchouli oil, against house dust mite, Dermatophagoides farinae. AB - This study characterized the acaricidal activity of constituents of patchouli oil extracted from (Pogostemon cablin (Blanco) BENTH) against the house dust mite, Dermatophagoides farinae. A new compound, 2-(1,3-dihydroxy-but-2-enylidene)-6 methyl-3-oxo-heptanoic acid (DHEMH), was isolated from patchouli oil and characterized by (1)H-NMR, (13)C-NMR, LC-MS and elemental analysis (EA). This active component was identified as the hydrolysate of pogostone. Fifteen other constituents found in patchouli oil were also identified by GC-MS, including patchouli alcohol and pogostone. LD(50) studies carried out over 24 h using contact toxicity tests identified DHEMH as the most toxic compound to D. farinae (2.04 MUg/cm(2)), followed by patchouli oil (6.11 MUg/cm(2)), benzyl benzoate (BP) (9.31 MUg/cm(2)) and dibutyl phthalate (DBP) (58.52 MUg/cm(2)). In vapor phase toxicity tests, all of these compounds were more effective in closed than open containers, indicating that the most efficient mode of delivery for these compounds is the vapor phase. These results indicate that DHEMH and patchouli oil merit further study as potential agents for the control of D. farinae. PMID- 22293477 TI - Prediction of ligand binding affinity using a multiple-conformations-multiple protonation scheme: application to estrogen receptor alpha. AB - A fast method that can predict the binding affinities of chemicals to a target protein with a high degree of accuracy will be very useful in drug design and regulatory science. We have been developing a scoring function for affinity prediction, which can be applied to extensive protein systems, and also trying to generate a prediction scheme that specializes in each target protein, with as high a predictive power as possible. In this study, we have constructed a prediction scheme with target-specific scores for estimating ligand-binding affinities to human estrogen receptor alpha (ERalpha), considering the major conformational change between agonist- and antagonist-bound forms and the change in protonation states of histidine at the ligand-binding site. The generated scheme calibrated with fewer training compounds (23 for the agonist-bound form, 17 for the antagonist-bound form) demonstrated good predictive power (a predictive r(2) of 0.83 for 154 validation compounds); this was also true for compounds with frameworks that were quite different from those of the training compounds. Our prediction scheme will be useful in drug development targeting ERalpha and in primary screening of endocrine disruptors, and provides a successful method of affinity prediction considering the major conformational changes in a protein. PMID- 22293478 TI - Twelve novel and diverse 16-norphragmalin-type limonoids from Chukrasia tabularis var. velutina. AB - A series of novel and structurally related C-15-acyl 16-norphragmalin-type limonoids, chuktabrins C-J (1-8) and chuktabularins U-X (9-12), were isolated from the stem bark of Chukrasia tabularis var. velutina. Their structures were established on the basis of detailed spectroscopic analysis, and the absolute configuration of compound 1 was determined by a single-crystal X-ray study using a mirror CuKalpha radiation. Compounds 7 and 8 were unprecedent C-15-acyl 16 norphragmalins with ketonic alkyl appendage at C-15, and compounds 4 and 8 were first examples of limonoid with a characteristic carbonate moiety esterified at OH-9/OH-8 or OH-1/OH-8 respectively. A biosynthetic pathway of these limonoids was reasonably presumed based on the novel and diverse structures isolated, which provides a new insight into the plausible biosynthesis of C-15-acyl 16 norphragmalin-type limonoids. The anti-inflammatory activity of major isolates were evaluated for inhibitory activity against lipopolysaccharide (LPS) induced nitric oxide (NO) production in macrophage (RAW264.7) cell line, with IC(50) value ranging from 2.40 to 16.90 MUM. PMID- 22293479 TI - Constituents from the roots of Taraxacum platycarpum and their effect on proliferation of human skin fibroblasts. AB - A MeOH extract from the roots of Taraxacum platycarpum has shown significant effects on the proliferation of normal human skin fibroblasts. Chemical analysis of the extract resulted in the isolation of 26 compounds, including eight new triterpenes, one new sesquiterpene glycoside, and seventeen known compounds. The structure of each new compound was established using NMR spectroscopy. Some triterpenes had a significant effect on the proliferation of normal human skin fibroblasts. PMID- 22293480 TI - Rupestines F-M, new guaipyridine sesquiterpene alkaloids from Artemisia rupestris. AB - Eight new guaipyridine sesquiterpene alkaloids, rupestines F-M (1-8) were isolated from the leaves of Artemisia rupestris and their structures were elucidated on the basis of 2D-NMR data. The absolute configurations of 1-8 have been assigned by comparison of their experimental and calculated circular dichroism (CD) spectra. PMID- 22293481 TI - New tricyclic alkaloids, cassiarins G, H, J, and K from leaves of Cassia siamea. AB - Four new alkaloids, cassiarins G, H, J, and K (1-4) which showed moderate antiplasmodial activity against Plasmodium falciparum 3D7, were isolated from the leaves of Cassia siamea (Leguminosae) and the structures of 1-4 were elucidated by 1D- and 2D-NMR analysis and X-ray crystallographic analysis. PMID- 22293482 TI - Synthesis and pharmacological evaluation of 2-(1-alkylpiperidin-4-yl)-n-[(1r)-1 (4-fluorophenyl)-2-methylpropyl]acetamide Derivatives as Novel Antihypertensive Agents. AB - We synthesized and evaluated the inhibitory activity of a series of 2-(1 alkylpiperidin-4-yl)-N-[(1R)-1-(4-fluorophenyl)-2-methylpropyl]acetamide derivatives against T-type Ca(2+) channels. Structure-activity relationship studies revealed that the position of the amide structure was important for the potent inhibitory activity toward T-type Ca(2+) channels. In addition, the introduction of an appropriate substituent on the pendant benzene ring played a crucial role for the selectivity towards T-type Ca(2+) channels over L-type Ca(2+) channels and the potent bradycardic activity of these derivatives. Oral administration of N-[(1R)-1-(4-fluorophenyl)-2-methylpropyl]-2-(1-{2-[2-(2 methoxyethoxy)phenyl]ethyl}piperidin-4-yl)acetamide (4f), which had superior selectivity for T-type Ca(2+) channels over L-type Ca(2+) channels, lowered blood pressure in spontaneously hypertensive rats without inducing reflex tachycardia, which is often caused by traditional L-type Ca(2+) channel blockers. PMID- 22293483 TI - 5-O-(4-[125 I]Iodobenzyl)-L-ascorbic acid: electrophilic radioiodination and biodistribution in mice. AB - As a part of our efforts to develop potential imaging agents for ascorbate bioactivity, 5-O-(4-[(125)I]iodobenzyl)-L-ascorbic acid ([(125)I]1) was prepared through a two-step sequence which involved radioiodo-destannylation of a protected tributylstannyl precursor 6, followed by hydrolysis in acidic methanol of the protecting groups in 61% overall radiochemical yield, with a radiochemical purity of over 98% and a specific activity of more than 15.4 GBq/MUmol. Tissue distribution of [(125)I]1 in tumor-bearing mice showed signs of distribution profiles similar to the reported results for 6-deoxy-6-[(18)F]fluoro-L-ascorbic (6-(18)FAsA) acid and 6-deoxy-6-[(131)I]iodo-L-ascorbic acid (6-(131)IAsA) but with notable differences in the adrenal glands, in which considerably lower uptake of radioactivity and rapid clearance with time were observed. Pretreatment of mice with a known inhibitor of ascorbate transport, sulfinpyrazone, did not produce any significant change in the adrenal uptake of radioactivity after injection of [(125)I]1 compared to the control, suggesting that uptake in the adrenal glands is independent of the sodium-dependent vitamin C transporter 2 transport mechanism. Introduction of a bulky substituent at C-5 on AsA, such as an iodobenzyloxy group, may not be suitable for the design of analogs that may still be able to maintain characteristic distribution properties in vivo seen with AsA itself. PMID- 22293484 TI - Three new phenolic glucosides from the roots of Rheum palmatum. AB - A novel naphthalene glucoside, rheumone A (1), with an unprecedented skeleton containing a seven-membered lactone, and two new compounds, 1-O-phloroglucinyl-2 O-galloyl-6-O-cinnamoyl-beta-D-glucoside (2) and chrysophanol 1-O-beta-D-(6'-O malonyl)glucoside (3), together with three known compounds (4-6) were isolated from the roots of Rheum palmatum. Their structures were elucidated mainly by spectroscopic analysis. These compounds were evaluated in vitro for their cytotoxicities towards human hepatocellular cancer cell lines Bel-7402 and Bel 7402/5Fu, and human gastric carcinoma cell line BGC-823. None of them showed cytotoxicity with IC(50) far beyond 50 MUM. PMID- 22293485 TI - Labdane-type diterpenoids from the rhizomes of Hedychium coronarium inhibit lipopolysaccharide-stimulated production of pro-inflammatory cytokines in bone marrow-derived dendritic cells. AB - The rhizomes of Hedychium coronarium have been used for the treatment of inflammation, skin diseases, headache, and sharp pain due to rheumatism in traditional medicine. From this plant, two new labdanes, 15-methoxylabda 8(17),11E,13-trien-16,15-olide (1) and 16-methoxylabda-8(17),11E,13-trien-15,16 olide (3), named hedycoronens A and B, as well as four known, labda-8(17),11,13 trien-16,15-olide (2), 16-hydroxylabda-8(17),11,13-trien-15,16-olide (4), coronarin A (5), and corronarin E (6) were isolated. Their chemical structures were elucidated by mass, 1D- and 2D-nuclear magnetic resonance (NMR) spectroscopy. They were evaluated for inhibitory effects on the lipopolysaccharide (LPS)-stimulated production of pro-inflammatory cytokines in bone marrow-derived dendritic cells. Among of them, compounds 1-3 were potent inhibitors of LPS-stimulated interleukin-6 (IL-6) and IL-12 p40, with IC(50) ranging from 4.1+/-0.2 to 9.1+/-0.3 MUM. Compounds 1 and 3 showed moderate inhibitory activity on the tumor necrosis factor-alpha (TNF-alpha) production with IC(50) values of 46.0+/-1.3 and 12.7+/-0.3 MUM. The remains of compounds showed inactivity. These results warrant further studies concerning the potential anti-inflammatory benefits of labdane-diterpenes from H. coronarium. PMID- 22293486 TI - Six new secoiridoids from the dried fruits of Ligustrum lucidum. AB - Six new secoiridoid constituents, named isoligustrosidic acid (1), 6'-O-trans cinnamoyl 8-epikingisidic acid (2), 6'-O-cis-cinnamoyl 8-epikingisidic acid (3), oleopolynuzhenide A (4), nuzhenals A (5) and B (6) were isolated from the dried fruits of Ligustrum lucidum AIT. Their structures were established on the basis of spectral and chemical data. PMID- 22293487 TI - Annonamine, a new aporphine alkaloid from the leaves of Annona muricata. AB - Atypical Parkinsonism in the Caribbean Island Guadeloupe is thought to be associated with the consumption of plants of the Annonaceae family, especially Annona muricata (soursop). In this study, a new aporphine alkaloid named annonamine (1) was isolated from the leaves of A. muricata L. together with four known benzylisoquinoline alkaloids (2-5). The structures of the isolated compounds were elucidated by the spectroscopic method. PMID- 22293488 TI - Release profiles of dexamethasone dipropionate from admixtures of steroid and heparinoid ointments prepared by different mixing methods. AB - Characterization and release profiles of commercial dexamethasone dipropionate (DDP) from an innovator and 2 generic ointments (Methaderm (IM), Promethasone (GP), and Mainvate (GM)) and their admixtures with heparinoid ointment (Hirudoid Soft) were investigated. The admixtures were prepared using 2 mixing methods (slab or rotation/revolution mixer). Microscopic and FT-Raman spectrometric analyses revealed that the ointments, except for IM, contained DDP crystals. A silicone membrane was used for the evaluation of the DDP permeation. The permeated DDP amounts from GP and GM were lower than that from IM, indicating that DDP solubility in the ointment vehicle affected the release of DDP from the ointment. No significant differences were observed in DDP release between IM alone and its admixture prepared using a slab; however, DDP release from the admixture prepared using a rotation/revolution mixer was significantly lower than those from IM alone and its admixture by slab. In the GP system, DDP release from the admixtures by the 2 mixing methods was higher than that from GP alone, whereas no significant difference in DDP release between the 2 mixing methods was observed. No significant differences were observed between the GM and admixtures. The apparent solubility of DDP in the admixtures as determined by the ultracentrifugal separation method indicated that the DDP amount in the liquid phase of admixtures with GP was 6 times higher than that of admixtures with IM or GM. Therefore, the apparent solubility of DDP in the liquid phase in the GP system might influence the DDP release in admixtures. PMID- 22293489 TI - An improved method for synthesis of 4,4-dimethylpyrazolone and application to dihydropyridazinone ring formation. AB - An improved method for 4,4-dimethylpyrazolone synthesis with t-butylcarbazate was described. The applicability of this method to dihydropyridazinone formation was demonstrated. This method is useful for suppressing the side reaction caused by the high nucleophilicity of hydrazine. PMID- 22293490 TI - Synthesis of 2-phenylbenzofuran derivatives and selective binding activities on estrogen receptor. AB - An improved chemical reaction protocol with short time and easy work-up was described here for 2-phenylbenzofuran derivatives. The final purified products, 2 phenylbenzofuran derivatives 5a-g and the intermediate diols 4a-g, were evaluated for their estrogen receptor (ER) binding affinity and selective activity in vitro. Among these fourteen tested compounds, 4g and 5g showed higher binding affinity on ER subtypes, ERalpha and ERbeta. Compound 4g exhibited preferable ERalpha binding, while 5g was more estrogen selective for ERbeta. The molecular docking was also performed to explore the detailed interactive interface between ER and the compounds. PMID- 22293491 TI - New cholestane glycosides from the leaves of Cordyline terminalis. AB - Four new cholestane glycosides (1-4) were isolated from the leaves of Cordyline terminalis (Agavaceae). The structures of the new compounds were determined on the basis of spectroscopic analysis and a few chemical transformations followed by chromatographic and spectroscopic analyses. PMID- 22293492 TI - New flavan and benzil isolated from Fissistigma latifolium. AB - Further investigation of the methanolic extract of Fissistigma latifolium resulted in two new compounds whose structures were assigned as 2,5,6,7 tetramethoxyflavan (1) and 2'-hydroxy-4',5',6'-trimethoxybenzil (2). These two compounds were determined on the basis of chemical and spectroscopic evidences. Compound 2 is the first report of benzil from Fissistigma species. 2,5,6,7 Tetramethoxyflavan (1) showed a potent inhibitory effect on superoxide anion production in formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)/cytochalasin B (CB)-activated human neutrophils. PMID- 22293493 TI - Critical role of mTOR in calcineurin inhibitor-induced renal cancer progression. PMID- 22293494 TI - The induction of polyploidy or apoptosis by the Aurora A kinase inhibitor MK8745 is p53-dependent. AB - Aurora kinases are mitotic serine/threonine protein kinases and are attractive novel targets for anticancer therapy. Many small-molecule inhibitors of Aurora kinases are currently undergoing clinical trials. Aurora A kinase is essential for successful mitotic transition. MK8745 is a novel and selective small-molecule inhibitor of Aurora A kinase. MK8745 induced apoptotic cell death in a p53 dependent manner when tested in vitro in cell lines of multiple lineages. Cells expressing wild-type p53 showed a short delay in mitosis followed by cytokinesis, resulting in 2N cells along with apoptosis. However, cells lacking or with mutant p53 resulted in a prolonged arrest in mitosis followed by endoreduplication and polyploidy. Cytokinesis was completely inhibited in p53-deficient cells, as observed by the absence of 2N cell population. The induction of apoptosis in p53 proficient cells was associated with activation of caspase 3 and release of cytochrome c but was independent of p21. Exposure of p53 wild-type cells to MK8745 resulted in the induction of p53 phosphorylation (ser15) and an increase in p53 protein expression. p53-dependent apoptosis by MK8745 was further confirmed in HCT 116 p53(-/-) cells transfected with wild-type p53. Transient knockdown of Aurora A by specific siRNA recapitulated these p53- dependent effects, with greater percent induction of apoptosis in p53 wild-type cells. In conclusion, our studies show p53 as a determining factor for induction of apoptosis vs. polyploidy upon inhibition of Aurora A. PMID- 22293495 TI - A sandfly fever virus outbreak in the East Mediterranean region of Turkey. AB - OBJECTIVES: To report a sandfly fever virus (SFV) outbreak that occurred in Kahramanmaras Province, Turkey. METHODS: We investigated the cases of 40 patients with a history of sandfly bites and with clinical findings, who were referred to our emergency service between July and August 2010. Serum samples of 19 patients were selected and analyzed using a commercial mosaic immunofluorescence test (IFT) to detect IgM and IgG antibodies against SFV. RESULTS: Sandfly fever was diagnosed in nine patients. All cases had a history of fly bite, and the clinical findings included fever, headache, myalgia, conjunctival hyperemia, and gastrointestinal symptoms such as diarrhea, nausea, and vomiting. In two patients, the diagnosis was confirmed by real-time PCR as sandfly Sicilian virus (SFSV). Laboratory findings in the patients included leukopenia, thrombocytopenia, and elevated levels of aspartate aminotransferase, alanine aminotransferase, creatine kinase, and C-reactive protein. All patients made a complete recovery with symptomatic treatment. CONCLUSIONS: SFV is endemic in the Mediterranean Basin and data regarding SFV activity in Turkey are limited. This is the first report of an SFV outbreak from Kahramanmaras Province, Turkey, and provides information on epidemiological, clinical, and laboratory aspects of SFV infections. PMID- 22293496 TI - A new methodological approach for PET implementation in radiotherapy treatment planning. AB - In this paper, a new methodological approach to using PET information in radiotherapy treatment planning has been discussed. Computed tomography (CT) represents the primary modality to plan personalized radiation treatment, because it provides the basic electron density map for correct dose calculation. If PET scanning is also performed it is typically coregistered with the CT study. This operation can be executed automatically by a hybrid PET/CT scanner or, if the PET and CT imaging sets have been acquired through different equipment, by a dedicated module of the radiotherapy treatment planning system. Both approaches have some disadvantages: in the first case, the bore of a PET/CT system generally used in clinical practice often does not allow the use of certain bulky devices for patient immobilization in radiotherapy, whereas in the second case the result could be affected by limitations in window/level visualization of two different image modalities, and the displayed PET volumes can appear not to be related to the actual uptake into the patient. To overcome these problems, at our centre a specific procedure has been studied and tested in 30 patients, allowing good results of precision in the target contouring to be obtained. The process consists of segmentation of the biological target volume by a dedicated PET/CT console and its export to a dedicated radiotherapy system, where an image registration between the CT images acquired by the PET/CT scanner and a large bore CT is performed. The planning target volume is contoured only on the large bore CT and is used for virtual simulation, to individuate permanent skin markers on the patient. PMID- 22293497 TI - Parametric [11C]flumazenil images. AB - OBJECTIVE: This [11C]flumazenil (FMZ) study evaluates the performance of various parametric analysis methods and their ability to detect statistically significant group differences. METHODS: Dynamic 60-min FMZ scans were performed in eight healthy and nine individuals with major depressive disorder. Parametric volume of distribution (VT) images were generated using a basis function method (BFM) implementation of the single tissue compartment model (1T) and Logan plot analysis, both with a metabolite-corrected arterial plasma input function. Parametric binding potential (BP ND) images were generated using multilinear reference tissue methods (MRTM0-4), reference Logan and receptor parametric mapping (RPM1-2), with pons as a reference region. Standardized uptake value (SUV) and SUV ratio-to-pons (SUVr) images were calculated over the time interval 30-40 and 20-60 min postinjection. The resulting VT, BP ND, SUV and SUVr values were compared with nonlinear regression values, using both the 1T model and the simplified reference tissue model. Statistical parametric mapping (SPM5) was used to detect group differences, with an emphasis on the bilateral parahippocampal gyri. RESULTS: BFM was more accurate than Logan, but showed more variability. Both RPM methods and MRTM2 showed the best average correlation with the simplified reference tissue model. In using SPM, SUV and SUVr images provided the best contrast between groups in the parahippocampal gyri, but provided large underestimation and overestimation in quantitative comparisons. BFM and RPM methods allowed for the determination of perfusion effects. CONCLUSION: Parametric Logan VT, MRTM2 and RPM1-2 BP ND methods allow the best quantitative comparison of FMZ binding between groups and show good discriminating performance in SPM analysis. PMID- 22293498 TI - High incidence of peritoneal implants in recurrence of intra-abdominal cancer revealed by 18F-FDG PET/CT in patients with increased tumor markers and negative findings on conventional imaging. AB - OBJECTIVE: The aim of this prospective study was to investigate the role of 18F fluorodeoxyglucose (18F-FDG) PET/CT in the diagnosis of recurrent intra-abdominal cancer in patients with increased tumor markers and negative findings on conventional imaging studies. METHODS: Seventy-three patients (30 men; age 61.1 +/- 11.5 years) with intra-abdominal cancer (colorectal, n=32; ovarian, n=18; gastric, n=7; pancreatic, n=7; cervical, n=4; endometrial, n=3; duodenal, n=1; and small bowel, n=1) and increasing levels of tumor markers during follow-up and negative CT, MRI or both underwent 125 18F-FDG PET/CT examinations. The final diagnosis was confirmed by histopathological findings in 22 patients, clinical follow-up (median of 12 months) in 13 patients,and repeated imaging with 18F-FDG PET/CT examinations in 38 patients. RESULTS: Of 73 cancer patients, 18F-FDG PET/CT identified recurrent disease in 52 patients and ruled out in 21 patients. 18F-FDG PET/CT scan was true positive (TP) in 49 patients, false positive in three patients, false negative in four patients, and true negative in 17 patients. In our study, the 18F-FDG-PET/CT scan had a sensitivity of 92.4%, a specificity of 85%, and an accuracy of 91%. Fourteen of 49 TP studies (28.5%) showed peritoneal implants only. Moreover, peritoneal implants were detected in additional nine of 49 TP studies (18.3%) presented with multiple lesions. Thus, half of the true-positive examination revealed peritoneal implants that CT or MRI had not depicted. CONCLUSION: The results of this study indicate a high incidence of peritoneal implants revealed by 18F-FDG PET/CT in the diagnosis of recurrent intra-abdominal cancer in patients with increasing tumor markers and negative findings on conventional imaging studies. PMID- 22293499 TI - Study on the distribution features of bone metastases in prostate cancer. AB - OBJECTIVES: The aim of this study was to explore the distribution features of metastatic bony lesions in prostate cancer. MATERIALS AND METHODS: Bone scans with 99mTc-methylene diphosphonate were performed in 144 patients with pathologically proven prostate cancer, and distribution regularity of metastatic bony lesions was analyzed retrospectively. RESULTS: A total of 2000 lesions of bone metastasis were detected in 102 patients, 28.9% of which were distributed in the ribs, 14.8% in thoracic vertebrae, 13.8% in the ilium, and 8.0% in the lumbar vertebrae. The distribution of metastatic bony lesions was correlated with the total number of lesions. The proportion of metastatic lesions of vertebrae and pelvis was up to 84.5% (49/58) in fewer bone metastases. The proportion gradually decreased with an increase in the total number of lesions, but the proportion of the bony lesions, except for the vertebrae and pelvis, gradually increased with an increase in the total number of lesions. Ninety-nine percent (903/912) of metastatic bony lesions, except for the vertebrae and pelvis, coexisted with metastasis of vertebrae or pelvis, whereas only 1.0% (9/912) of those were detected in no metastasis of the vertebrae and pelvis; their difference was significant (chi2=876.4, P=0.000). About 98.8% (571/578) of metastatic costal lesions coexisted with vertebrae metastasis, but only 1.2% (7/578) of these were detected in no metastasis of vertebrae; their difference was significant (chi2=550.3, P=0.000). The difference between left body and right body was not significant (chi=1.3, P=0.249). CONCLUSION: Metastatic bony lesions of prostate cancer are located mainly in the vertebrae and pelvis in the early stage. The distribution of metastatic bony lesions is not only characterized by spreading to left body and right body randomly, but also presents the tendency of developing with orderliness to a certain extent in the whole body. PMID- 22293500 TI - MIG-13 controls anteroposterior cell migration by interacting with UNC-71/ADM-1 and SRC-1 in Caenorhabditis elegans. AB - The transmembrane protein MIG-13 is a key regulator required for anterior migration of neural cells in Caenorhabditis elegans, but the signaling mechanisms involved remain unknown. Here, we isolated a suppressor mutation in the unc 71/adm-1 gene, which rescued the AVM neuron migration defect in mig-13 mutants. Genetic analyses revealed that UNC-71 at least partly acts downstream of MIG-13 and has an inhibitory effect on the anterior cell migration. The unc-71 mutation also rescued the anterior migration defect of AVM neuron in src-1 mutants. These findings suggest that MIG-13 controls anteroposterior cell migration by interacting with UNC-71 and SRC-1 in C. elegans. PMID- 22293501 TI - Oligomeric interactions of TGF-beta and BMP receptors. AB - Transforming growth factor-beta (TGF-beta) and bone morphogenetic protein (BMP) cytokines participate in a multiplicity of ways in the regulation of numerous physiological and pathological processes. Their wide-ranging biological functions are controlled by several mechanisms, including regulation of transcription, complex formation among the signaling receptors (oligomerization) and with co receptors, binding of the receptors to scaffolding proteins or their targeting to specific membrane domains. Here, we address the generation of TGF-beta and BMP receptor homo- and hetero-oligomers and its roles as a mechanism capable of fast regulation of signaling by these crucial cytokines. We examine the available biochemical, biophysical and structural evidence for the ternary structure of these complexes, and the possible roles of homomeric and heteromeric receptor oligomers in signaling. PMID- 22293503 TI - HBXIP upregulates CD46, CD55 and CD59 through ERK1/2/NF-kappaB signaling to protect breast cancer cells from complement attack. AB - Hepatitis B X-interacting protein (HBXIP) is able to enhance migration of breast cancer cells. However, the role of HBXIP in regulation of complement-dependent cytotoxicity (CDC) in breast cancer is not understood. Here, we report that HBXIP contributes to protecting breast cancer cells from CDC by upregulating membrane bound complement regulatory protein (mCRPs), including CD46, CD55 and CD59. We found that HBXIP upregulated mCRPs through activating p-ERK1/2/NF-kappaB. Interestingly, the knockdown of CD59 was able to block the HBXIP-enhanced breast tumor growth in animal. Thus, we conclude that HBXIP upregulates CD46, CD55 and CD59 through p-ERK1/2/NF-kappaB signaling to protect breast cancer from CDC. PMID- 22293502 TI - Selenomodification of tRNA in archaea requires a bipartite rhodanese enzyme. AB - 5-Methylaminomethyl-2-selenouridine (mnm(5)Se(2)U) is found in the first position of the anticodon in certain tRNAs from bacteria, archaea and eukaryotes. This selenonucleoside is formed in Escherichia coli from the corresponding thionucleoside mnm(5)S(2)U by the monomeric enzyme YbbB. This nucleoside is present in the tRNA of Methanococcales, yet the corresponding 2-selenouridine synthase is unknown in archaea and eukaryotes. Here we report that a bipartite ybbB ortholog is present in all members of the Methanococcales. Gene deletions in Methanococcus maripaludis and in vitro activity assays confirm that the two proteins act in trans to form in tRNA a selenonucleoside, presumably mnm(5)Se(2)U. Phylogenetic data suggest a primal origin of seleno-modified tRNAs. PMID- 22293504 TI - Feeding difficulties in children with cerebral palsy. AB - Feeding difficulties are common in children with cerebral palsy and have an effect on growth, nutritional state, general health, social interaction and behaviour and developmental outcomes. Many factors have an effect on feeding ability. Identification of these factors and amelioration of their impact on feeding difficulties is essential to promote adequate growth and nutrition. Appropriate assessment and management is best achieved by a multiprofessional team skilled in the care of children with cerebral palsy and feeding impairments. Feeding difficulties must be considered within the wider context of family and social circumstance. PMID- 22293505 TI - A novel multiplex real-time PCR assay for the detection and quantification of HPV16/18 and HSV1/2 in cervical cancer screening. AB - Infection with human papillomavirus (HPV), particularly HPV16 and HPV18, is the main cause of invasive cervical cancer, although other factors such as herpes simplex virus (HSV) may act in conjunction with HPV in this context. To explore the possibility of developing a system for rapid diagnosis and clinical screening of cervical cancer, we developed a multiplex real-time PCR assay that can simultaneously detect and quantify HPV16/18 and HSV1/2. To evaluate its possibilities and practical uses, 177 samples collected from patients with suspected HPV and HSV infection in exfoliated cervical cells, genital herpes or labial herpes were tested by multiplex real-time PCR and compared with results obtained by DNA sequencing. Each virus was detected over a range from 1.0 * 10(1) to 1.0 * 10(7) copies/reaction. The clinical sensitivity was 100% for HPV16/18 and HSV1/2. The clinical specificity was 97.1% for HPV16, 98.1% for HPV18, 97.0% for HSV1 and 96.0% for HSV2. The kappa value was 0.96 for HPV16, 0.92 for HPV18, 0.94 for HSV1 and 0.93 for HSV2, when DNA sequencing was used as the reference standard. In summary, this novel multiplex real-time PCR allows the rapid and specific detection of HPV16/18 and HSV1/2, as well as coinfection with HPV and HSV, in clinical samples. In the future, this multiplex real-time PCR assay will assist in cervical cancer screening, viral treatment evaluation and epidemiological studies in which high throughput analysis is required. PMID- 22293506 TI - Effects of ritonavir-boosted darunavir, atazanavir and lopinavir on adipose functions and insulin sensitivity in murine and human adipocytes. AB - BACKGROUND: Ritonavir-boosted protease inhibitors (PIs) could adversely affect metabolism and adipose tissue to different extents, depending on the molecule. Using drugs with minimal adverse metabolic effects is an important consideration in at-risk HIV-infected patients. In vitro adipocyte models can be useful for comparing the effects of different PIs. METHODS: We compared the effects of darunavir, darunavir/ritonavir, atazanavir/ritonavir and lopinavir/ritonavir in murine and human adipocytes on differentiation, mitochondrial function, reactive oxygen species (ROS) production and insulin sensitivity. RESULTS: In human and murine adipocytes, differentiation evaluated by lipid content and protein expression of adipogenic markers, mitochondrial function evaluated by aggregation of the cationic dye JC-1 and by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide lysis, and mitochondrial mass evaluated by MitoTracker fluorescence and the expression of mitochondrial proteins were unaffected by darunavir, mildly affected by darunavir/ritonavir and further altered by atazanavir/ritonavir and lopinavir/ritonavir. ROS production was unaltered by darunavir and darunavir/ritonavir but was increased by lopinavir/ritonavir and atazanavir/ritonavir. Regarding insulin sensitivity, darunavir and darunavir/ritonavir had no significant effect on insulin activation of protein kinase B (Akt/PKB) and MAP kinase and of glucose transport, whereas lopinavir/ritonavir and atazanavir/ritonavir partly impaired the effect of insulin. The effect of atazanavir/ritonavir was generally milder than that of lopinavir/ritonavir. CONCLUSIONS: The various PIs differentially modified adipocyte functions. Darunavir alone did not affect adipocyte functions and only modestly altered differentiation and mitochondrial function when associated with ritonavir. Lopinavir/ritonavir adversely affected differentiation and lipid content, mitochondrial function, ROS production and insulin sensitivity, and the effect of atazanavir/ritonavir was intermediate. Thus, in vitro, darunavir/ritonavir presented a safer metabolic profile on adipocytes than atazanavir/ritonavir and lopinavir/ritonavir. PMID- 22293507 TI - Do hyperbaric oxygen-induced seizures cause brain damage? AB - It is commonly accepted that hyperbaric oxygen-induced seizures, the most severe manifestation of central nervous system oxygen toxicity, are harmless. However, this hypothesis has not been investigated in depth. We used apoptotic markers to determine whether cells in the cortex and hippocampus were damaged by hyperbaric oxygen-induced seizures in mice. Experimental animals were exposed to a pressure of 6 atmospheres absolute breathing oxygen, and were randomly assigned to two groups sacrificed 1h after the appearance of seizures or 7 days later. Control groups were not exposed to hyperbaric oxygen. Caspase 9, caspase 3, and cytochrome c were used as apoptotic markers. These were measured in the cortex and the hippocampus, and compared between the groups. Levels of caspase 3, cytochrome c, and caspase 9 in the hippocampus were significantly higher in the hyperbaric oxygenexposed groups compared with the control groups 1 week after seizures (p<0.01). The levels of two fragments of caspase 9 in the cortex were higher in the control group compared with the hyperbaric oxygen-exposed group 1h after seizures (p<0.01). Hyperbaric oxygen-induced seizures activate apoptosis in the mouse hippocampus. The reason for the changes in the cortex is not understood. Further investigation is necessary to elucidate the mechanism underlying these findings and their significance. PMID- 22293508 TI - Governments and drug companies pledge to eliminate 10 neglected tropical diseases by 2020. PMID- 22293509 TI - "No win, no fee" system is proving costly to NHS, report says. PMID- 22293510 TI - Doctor who helped locate bin Laden family worked for the CIA. PMID- 22293511 TI - Competition can help NHS but must be used with care, report says. PMID- 22293512 TI - Radiation exposure and image quality of normal computed tomography brain images acquired with automated and organ-based tube current modulation multiband filtering and iterative reconstruction. AB - OBJECTIVES: We sought to determine whether radiation dose can be reduced and image quality improved in computed tomography (CT) images of the brain that were acquired with automated exposure control (AEC), organ-based tube current modulation (TCM), multiband filtration (MBF), and iterative reconstruction in image space (IRIS). METHODS: An Alderson-Rando-phantom, equipped with thermoluminescent dosimeters, was used to determine the radiation exposure of organs within the head and neck by different CT brain scan modes. We measured the noise and signal-to-noise ratios and subjectively graded quality criteria in different territories of the brain in spiral CT images of 150 patients. We also derived the radiation exposure from the patient protocols. RESULTS: In the phantom, AEC and TCM reduced the radiation exposure of the lenses, cerebrum, cerebellum, and thyroid gland by 41.9%, 34.5%, 30.5%, and 34.9%, respectively. Brain CT scans from patients investigated with AEC, TCM, MBF, and IRIS were found to have significantly better image quality than with conventional filtered back projection. In addition, the CT dose index and dose-length product were significantly lower with AEC, TCM, MBF, and IRIS by 24.1% and 20.2%, respectively. CONCLUSION: The combination of AEC, TCM, MBF, and IRIS improves image quality while radiation exposure can be reduced, particularly in dose sensitive organs, such as the lenses and thyroid gland. PMID- 22293513 TI - Initial experience with identifying high-grade prostate cancer using diffusion weighted MR imaging (DWI) in patients with a Gleason score <= 3 + 3 = 6 upon schematic TRUS-guided biopsy: a radical prostatectomy correlated series. AB - INTRODUCTION: Diffusion-weighted magnetic resonance (MR) imaging (DWI) might be able to fulfill the need to accurately identify high-grade prostate carcinoma, in patients initially selected for active surveillance in the Prostate Specific Antigen (PSA) screening era based on transrectal ultrasound-guided biopsy Gleason score. We aimed to determine whether DWI is able to correctly identify those patients with a biopsy Gleason score of <= 3 + 3 = 6, but harboring Gleason 4 and/or 5 components in their radical prostatectomy (RP) specimen. MATERIALS AND METHODS: Whole-mount RP specimens were used to identify regions of interest corresponding with tumor on the DWI-derived apparent diffusion coefficient (ADC) maps in 23 patients with a Gleason <= 3 + 3 = 6 on biopsy. ADC values were correlated with RP Gleason grades. Statistical analysis was performed by calculating area under the receiver operating characteristic curve for identification of prostate cancer with Gleason 4 and/or 5 components using DWI, and Mann-Whitney U testing was performed to detect differences in median ADC values for tumors with presence of Gleason grade 4 and/or 5 versus a highest Gleason grade of <= 3 on RP. RESULTS: A diagnostic accuracy of median ADC values for identifying patients subject to transrectal ultrasound-guided biopsy undergrading with an area under the receiver operating characteristic curve of 0.88 was established using RP Gleason score as a reference. In patients harboring a Gleason 4 and/or 5 component, the median ADC was 0.86 * 10(-3) mm/s (standard deviation +/- 0.21), whereas patients harboring no Gleason 4 and/or 5 component displayed a median ADC of 1.16 * 10(-3) mm/s (standard deviation +/- 0.19) for the single tumor slice with the lowest median ADC (P < 0.002). CONCLUSIONS: DWI is able to predict the presence of high-grade tumor in patients with a Gleason <= 3 + 3 = 6 on biopsy, providing important information for treatment decisions. PMID- 22293514 TI - A case of a potential drug interaction between clobazam and etravirine-based antiretroviral therapy. AB - The cytochrome P450 isoforms primarily involved in clobazam metabolism are CYP3A4 and 2C19. Drugs that modulate these enzymes would then be expected to alter the exposure of clobazam and its major metabolites. Etravirine, a second-generation non-nucleoside reverse transcriptase inhibitor has been shown to induce CYP3A4, while inhibiting CYP2C9 and CYP2C19. We report a case in which a potential drug interaction between clobazam and etravirine may have led to increased concentrations of clobazam and its pharmacologically active metabolite, N desmethylclobazam, causing neurotoxic symptoms. PMID- 22293515 TI - Detection and molecular characterization of porcine circovirus type 2 (PCV2) from piglets with exudative epidermitis in Uruguay. AB - Porcine circovirus type 2 (PCV2) is an economically important emerging pathogen associated with distinct syndromes and diseases in swine, collectively known as porcine circovirus associated diseases (PCVAD). The main purpose of this study was to investigate the presence of PCV2 in piglets affected with exudative epidermitis (EE) in Uruguay. In addition we aimed to analyze the phylogenetic relationships of the isolated strains. In June 2011 an outbreak of EE detected in a small herd was reported. Piglets presented skin lesions compatible with EE and symptoms associated with postweaning multisystemic wasting syndrome (PMWS) were also observed. Sera from affected and healthy animals were tested for the presence of viral DNA. Exclusively, diseased piglets were infected with PCV2. Phylogenetic analysis showed that PCV2 isolates belonged to PCV2b genotype. We report the detection and molecular characterization of PCV2 strains for the first time in Uruguay. PMID- 22293516 TI - Methods for imaging DNA in liquid with lateral molecular-force microscopy. AB - Shear force microscopy is not normally associated with the imaging of biomolecules in a liquid environment. Here we show that the recently developed scattered evanescent wave (SEW) detection system, combined with custom-designed vertically oriented cantilevers (VOCs), can reliably produce true non-contact images in liquid of DNA molecules. The range of cantilever spring constants for successful shear force imaging was experimentally identified between 0.05 and 0.09 N m(-1). Images of lambda-DNA adsorbed on mica in distilled water were obtained at scan rates of 8000 pixels s(-1). A new constant-height force mapping mode for VOCs is also presented. This method is shown to control the vertical position of the tip in the sample plane with better than 1 nm accuracy. The force mode is demonstrated by mapping the shear force above lambda-DNA molecules adsorbed on mica in a liquid environment at different tip-sample separations. PMID- 22293517 TI - SpliceGrapher: detecting patterns of alternative splicing from RNA-Seq data in the context of gene models and EST data. AB - We propose a method for predicting splice graphs that enhances curated gene models using evidence from RNA-Seq and EST alignments. Results obtained using RNA Seq experiments in Arabidopsis thaliana show that predictions made by our SpliceGrapher method are more consistent with current gene models than predictions made by TAU and Cufflinks. Furthermore, analysis of plant and human data indicates that the machine learning approach used by SpliceGrapher is useful for discriminating between real and spurious splice sites, and can improve the reliability of detection of alternative splicing. SpliceGrapher is available for download at http://SpliceGrapher.sf.net. PMID- 22293518 TI - Electronic sensitivity of a single-walled carbon nanotube to internal electrolyte composition. AB - Carbon nanotubes (CNTs) are well known as materials for nanoelectronics and show great potential to be used as the sensing elements in chemical and biological sensors. Recently, CNTs have been shown to be effective nanofluidic channels and the transport of substances through small diameter CNTs is intrinsically fast, selective, and operates at the single molecule level. It has been shown that the transport characteristics of semiconducting single-walled CNT (SWCNT) field effect transistors (FETs) are sensitive to internal water wetting. We report here that the characteristics of semiconducting SWCNT FETs are also sensitive to the concentration, pH and ion type of the ionic solution when the electrolyte is inside the CNT. Such sensitivity is not observed at the outside surface of a semiconducting SWCNT. This opens a new avenue for building new types of CNT sensor devices in which the SWCNT concurrently functions as a nanochannel and an electronic detector. PMID- 22293519 TI - Technology Drivers for Quality by Design (QbD) Implementation for Biopharmaceutical Products. PMID- 22293520 TI - Letter to the editor. PMID- 22293521 TI - Author response. PMID- 22293522 TI - Modes of Degradation and Impurity Characterization in rhPTH (1-34) during Stability Studies. AB - During storage of recombinant human parathyroid hormone (rhPTH) (amino acid residues 1-34) at 25 +/- 2 degrees C, several impurities were obtained, which were detected by the tricine sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and reversed-phase high-performance liquid chromatography (RP-HPLC) methods. To characterize the impurities generated, forceful chemical oxidation and deamidation was done. The oxidized positions were characterized by cyanogen bromide (CNBr) cleavage followed by liquid chromatography/mass spectrometry (LCMS) and further confirmed through N-terminal sequencing. Three oxidized variants were observed: sulfoxide of Met8 and Met18 and a variant comprising sulfoxide forms of both the methionine residues. LCMS results confirmed the presence of deamidated (+1 Da) and succinimide (-17 Da) variants. The low molecular weight impurities observed by tricine SDS-PAGE was confirmed to be peptide fragments by N-terminal sequencing and LCMS, resulting from cleavage at the C-terminal of asparagine (Asn)16, Asn33, and Asp30. Studies showed that rhPTH (1-34) undergoes oxidation, deamidation, and peptide bond cleavage during storage at pH 4.0 in acetate buffer. LAY ABSTRACT: Unlike currently licensed therapies to manage osteoporosis, parathyroid hormone (PTH) and its analogs represent a new class of anabolic agents, which act primarily to inhibit bone resorption and remodeling. The hormone's recombinant form is a bioactive peptide, 1-34 residues, which is inherently very unstable. Prior understanding of the molecular degradation pathway will help in development of a process that will yield a better product with respect to its quality and stability. The current work focuses on detailed characterization of the product related impurities generated during storage of recombinant human PTH. The study depicted the various routes through which the molecule can degrade during its shelf life. Through a combination of forced degradation and accelerated study, it was established that the impurities were generated owing to oxidation, deamidation, and peptide bond cleavage of/at various amino acid residues. Until this study, it was presumed that oxidation is the primary route of degradation in PTH and most of the published reports were on native (1-84) forms of the hormone. The present research confirms that the recombinant hormone (1-34) degraded not only because of oxidation but that deamidation and peptide bond cleavage are also prominent modes of degradation. Therefore, owing to the unstable nature of the molecule it is suggested that stringent conditions should be maintained during manufacturing to obtain a stable molecule with fewer impurities. PMID- 22293523 TI - Investigating Liquid Leak from Pre-Filled Syringes upon Needle Shield Removal: Effect of Air Bubble Pressure. AB - This study is to investigate the effect of headspace air pressure in pre-filled syringes on liquid leak (dripping) from the syringe needle upon needle shield removal. Drip tests to measure drip quantity were performed on syringes manually filled with 0.5 or 1.0 mL of various aqueous solutions. Parameters assessed included temperature (filling and test), bulk storage conditions (tank pressure and the type of the pressurized gas), solution composition (pure water, 0.9% sodium chloride, and a monoclonal antibody formulation), and testing procedures. A headspace pressure analyzer was used to verify the drip test method. Results suggested that leakage is indeed caused by headspace pressure increase, and the temperature effect (ideal gas expansion) is a major, but not the only, factor. The dissolved gases in the liquid bulk prior to or during filling may contribute to leakage, as these gases could be released into the headspace due to solubility changes (in response to test temperature and pressure conditions) and cause pressure increase. Needle shield removal procedures were found to cause dripping, but liquid composition played little role. Overall, paying attention to the processing history (pressure and temperature) of the liquid bulk is the key to minimize leakage. The headspace pressure could be reduced by decreasing liquid bulk storage pressure, filling at a higher temperature, or employing lower solubility gas (e.g., helium) for bulk transfer and storage. Leakage could also be mitigated by simply holding the syringe needle pointing upward during needle shield removal. LAY ABSTRACT: Substantial advances in pre-filled syringe technology development, particularly in syringe filling accuracy, have been made. However, there are factors, as subtle as how the needle shield (or tip cap) is removed, that may affect dosing accuracy. We recently found that upon removal of the tip cap from a syringe held vertically with needle pointed downwards, a small amount of solution, up to 3-4% of the 1 mL filled volume or higher for filled volume of <1 mL, leaked out from the needle. This paper identified the root causes of this problem and offered solutions from the perspectives of the syringe fill process and the end user procedure. The readers will benefit from this paper by understanding how each process step prior to and during syringe filling may affect delivery performance of the pre-filled syringe device. PMID- 22293524 TI - Carrier tests to assess the effective sporicidal concentration of a liquid chemical disinfectant for a sanitization program. AB - The aim of the present investigation was to evaluate the microbial efficacy against highly resistant bacterial spores on different substrates using the lowest effective concentration of a market liquid sporicide based on peracetic acid. The validation was carried out following modified European regulatory agencies procedures or test methods and USP guidelines, employing carriers of materials usually treated with the sporicidal solution and present in grade A cleanrooms and spores of four different microorganisms: Bacillus subtilis and Clostridium sporogenes, both from the ATCC collection, and Bacillus cereus and Bacillus sphaericus as environmental isolates. A statistical evaluation of data was made to estimate the variance for different study conditions. The experiments highlighted that 70% suitable dilution of the ready-to-use peracetic acid solution was effective in both clean and dirty conditions, showing at least 2 log spore reduction after treatment. To obtain effective sporicidal action on the surfaces in cleanrooms it is sufficient to use a sporicidal solution with a ready to-use concentration of 70% while ensuring a contact time of 10 min. In any case, the reduction of sporicide concentration ensures a high degree of disinfection and provides a consumption savings. LAY ABSTRACT: Wide-spectrum disinfectants are used in the pharmaceutical industry for the decontamination of work surfaces and equipment, but these products have some degree of toxicity for operators. This work arises from the needs of pharmaceutical companies to find the lowest effective concentration of sanitizers in order to reduce toxicity to personnel. The sanitizer used in the study was a market liquid sporicide based on peracetic acid. When we started our work no similar studies were reported in the literature, so we took European regulatory agencies and USP guidelines as a starting point, employing carriers of hard, non-porous materials usually treated with the sporicidal solution and present in sterile rooms and spores of four different microorganisms. The experiments highlighted that it is sufficient to use a 70% sporicidal solution concentration with a contact time of 10 min to reduce the number of spores to acceptable values for medicinal production. The reduction of sporicide concentration both ensures a high degree of disinfection and provides a safer working environment and consumption savings. PMID- 22293525 TI - A method to quantitatively define and assess the risk of cosmetic glass defects on tubing glass vials. AB - The pharmaceutical and biotechnology industries have long been challenged with setting appropriate cosmetic defect size acceptance criteria on glass vials. Limits are rarely data-driven and scarce information is available on defect survivability through shipping and handling downstream of final product visual inspection. This study was undertaken to quantitatively understand cosmetic defect dynamics on glass vials and their impact on patient safety. Scratch and bruise defects were artificially manufactured on product or placebo-filled, inspected, and glass defect-free tubing vials. The vials were processed and filled using commercial filling operations (i.e., vial washing, heat tunnel, conveyors, lyophilization, etc.). The defects were quantitatively characterized, subjected to automated packaging simulations, manually packaged in the approved commercial configurations, and subjected to ASTM Level I (highest intensity) shipping simulations in both pallet and small package configurations. The defects showed no statistically significant or applicable level of propagation, post packaging and shipping simulation. Additionally, all test vials were subjected to dye leak testing, post-shipping simulation. All vials, except for one, met acceptance criteria for dye leak testing. Data-driven cosmetic defect dimensions for scratches and bruises were established based on this study. LAY ABSTRACT: When delivering life saving medicines from the manufacturing plant to the patient, it is of great importance that the medicines arrive without damage that might harm the patient. In the case of medicines filled into glass vials, it is paramount that manufacturers understand whether minor cosmetic defects in the glass (such as small scratches and bruises) may weaken the vial enough to cause damage that might allow contamination of the contents. This study was performed to determine if scratches and bruises on the glass vials might propagate during operations that occur downstream of the manufacturer's final vial inspection. The study vials were filled with product or placebo on the commercial filling lines to fully simulate environmental factors in a typical run. Scratches and bruises were then artificially created on the vials. Each defect was measured microscopically and labeled. The study population was then manually packaged into the approved configurations and subjected to the highest level intensity shipping simulations (ASTM Level 1). Upon completion of the simulations, the vials were unpackaged and defects re-measured microscopically. The defects showed no statistically significant or applicable level of propagation. Additionally, all test vials were subjected to dye leak testing, post-shipping simulation. All vials, except for one, met acceptance criteria. Data-driven cosmetic defect dimensions for scratches and bruises were established based on this study. PMID- 22293526 TI - A review of cleanroom microflora: types, trends, and patterns. AB - Cleanroom microflora are of importance for microbiologists and quality control personnel in order to assess changes in trends. Shifts in the types of microflora may indicate deviations from the "norm" such as resistant strains or problems with cleaning practices. Given the few published studies of the typical microflora, this paper uniquely reviews over 9000 microbial isolates from a range of different grades of cleanroom. The paper concludes that the typical flora are primarily those associated with human skin (Gram-positive cocci), although microorganisms from other sources such as the environment (Gram-positive rods) and water (Gram-negative rods) are also detected, although in lower numbers. LAY ABSTRACT: It is of importance that pharmaceutical manufacturers and healthcare pharmacies review the types and numbers of microorganisms found within their clean areas. Such examination should be carried out over a long period of time so that the complete picture can be revealed. This is important in order to understand if certain species are being recovered pose a product or environmental risk and to check if the cleaning and sanitization practices are effective. PMID- 22293527 TI - Comparison of deterministic and stochastic simulation for capacity extension of high-purity water delivery systems. AB - This work presents a deterministic and a stochastic model for the simulation of industrial-size deionized water and water for injection (DI/WFI) systems. The objective of the simulations is to determine if additional DI/WFI demand from future production processes can be supported by an existing DI/WFI system. The models utilize discrete event simulation to compute the demand profile from the distribution system; they also use a continuous simulation to calculate the variation of the water level in the storage tank. Whereas the deterministic model ignores uncertainties, the stochastic model allows for both volume and schedule uncertainties. The Monte Carlo method is applied to solve the stochastic method. This paper compares the deterministic and stochastic models and shows that the deterministic model may be suitable for most applications and that the stochastic model should only be used if found necessary by the deterministic simulation. The models are programmed within Excel 2003 and are available for download as open public domain software (1), allowing for public modifications and improvements of the model. The proposed models may also be utilized to determine size or analyze the performance of other utilities, such as heat transfer media, drinking water, etc. LAY ABSTRACT: Water for injection (WFI) and other pharmaceutical water distribution systems are notoriously difficult to analyze analytically due to the highly dynamic variable demand that is drawn from these systems. Discrete event simulation may provide an answer where the typical engineering approach of utilizing a diversity factor fails. This paper develops an Excel based deterministic and stochastic model for a WFI system with the latter allowing for the modeling of offtake volume and schedule uncertainty. The paper also compares the deterministic and stochastic models and shows that the deterministic model may be suitable for most applications while the stochastic model should only be used if found necessary. The models are available for download as open public domain software allowing for modifications and improvements of the model. PMID- 22293528 TI - An improved method for visualizing the morphology of lyophilized product cakes. AB - Due to low optical contrast, the morphology of lyophilized product cakes is difficult to observe and photograph. Furthermore, internal structures are normally not visible unless the cake is fractured. Because most lyophilized substances are hygroscopic and quite fragile, the product cake, once removed from the vial, will rapidly degrade. We propose herein a technique that allows a lyophilized product cake to be preserved, manipulated, and easily observed outside the vial. This technique yields high-quality, cross sectional images that reveal intricate fine structures without the use of expensive specialized equipment. PMID- 22293529 TI - RNA therapy for polyglutamine neurodegenerative diseases. AB - Polyglutamine neurodegenerative diseases result from the expansion of a trinucleotide CAG repeat, encoding a polyglutamine tract in the disease-causing protein. The process by which each polyglutamine protein exerts its toxicity is complex, involving a variety of mechanisms including transcriptional dysregulation, proteasome impairment and mitochondrial dysfunction. Thus, the most effective and widely applicable therapies are likely to be those designed to eliminate production of the mutant protein upstream of these deleterious effects. RNA-based approaches represent promising therapeutic strategies for polyglutamine diseases, offering the potential to suppress gene expression in a sequence specific manner at the transcriptional and post-transcriptional levels. In particular, gene silencing therapies capable of discrimination between mutant and wildtype alleles, based on disease-linked polymorphisms or CAG repeat length, might prove crucial in cases where a loss of wild type function is deleterious. Novel methods, such as gene knockdown and replacement, seek to eliminate the technical difficulties associated with allele-specific silencing by avoiding the need to target specific mutations. With a variety of RNA technologies currently being developed to target multiple facets of polyglutamine pathogenesis, the emergence of an effective therapy seems imminent. However, numerous technical obstacles associated with design, discrimination and delivery must be overcome before RNA therapy can be effectively applied in the clinical setting. PMID- 22293530 TI - Comparison of sterols and fatty acids in two species of Ganoderma. AB - BACKGROUND: Two species of Ganoderma, G. sinense and G. lucidum, are used as Lingzhi in China. Howerver, the content of triterpenoids and polysaccharides, main actives compounds, are significant different, though the extracts of both G. lucidum and G. sinense have antitumoral proliferation effect. It is suspected that other compounds contribute to their antitumoral activity. Sterols and fatty acids have obvious bioactivity. Therefore, determination and comparison of sterols and fatty acids is helpful to elucidate the active components of Lingzhi. RESULTS: Ergosterol, a specific component of fungal cell membrane, was rich in G. lucidum and G. sinense. But its content in G. lucidum (median content 705.0 MUg.g 1, range 189.1-1453.3 MUg.g-1, n = 19) was much higher than that in G. sinense (median content 80.1 MUg.g-1, range 16.0-409.8 MUg.g-1, n = 13). Hierarchical clustering analysis based on the content of ergosterol showed that 32 tested samples of Ganoderma were grouped into two main clusters, G. lucidum and G. sinense. Hierarchical clustering analysis based on the contents of ten fatty acids showed that two species of Ganoderma had no significant difference though two groups were also obtained. The similarity of two species of Ganoderma in fatty acids may be related to their antitumoral proliferation effect. CONCLUSIONS: The content of ergosterol is much higher in G. lucidum than in G. sinense. Palmitic acid, linoleic acid, oleic acid, stearic acid are main fatty acids in Ganoderma and their content had no significant difference between G. lucidum and G. sinense, which may contribute to their antitumoral proliferation effect. PMID- 22293531 TI - Current evidence on intradermal influenza vaccines administered by SoluviaTM licensed micro injection system. AB - Among the several strategies explored for (1) the enhancement of the immune response to influenza immunization, (2) the improvement of the vaccine acceptability and (3) the overcoming of the egg-dependency for vaccine production, intradermal administration of influenza vaccine emerges as a promising alternative to conventional intramuscular route, thanks to the recent availability of new delivery devices and the perception of advantages in terms of immunogenicity, safety, reduction of antigen content and acceptability. Data from clinical trials performed in children, adults < 60 y and elderly people and post marketing surveillance demonstrate that actually, licensed intradermal influenza vaccines, IntanzaTM 9 and 15 ug and FluzoneTM Intradermal, administered by the microinjection system SoluviaTM, show an excellent acceptability, tolerability and safety profile. Formulations containing 9 and 15 MUg per strain demonstrate, respectively, comparable and superior immunogenicity than conventional intramuscular vaccines. Licensed intradermal influenza vaccines can be considered a valid alternative to standard intramuscular vaccination offering significant advantages in low-responder populations and helping to increase influenza vaccination coverage rates especially in people with fear of needles or high apprehension associated with annual vaccination. PMID- 22293532 TI - Lessons learned about collaborative evaluation using the Capacity for Applying Project Evaluation (CAPE) framework with school and district leaders. AB - Schools, districts, and state-level educational organizations are experiencing a great shift in the way they do the business of education. This shift focuses on accountability, specifically through the expectation of the effective utilization of evaluative-focused efforts to guide and support decisions about educational program implementation. In as much, education leaders need specific guidance and training on how to plan, implement, and use evaluation to critically examine district and school-level initiatives. One specific effort intended to address this need is through the Capacity for Applying Project Evaluation (CAPE) framework. The CAPE framework is composed of three crucial components: a collection of evaluation resources; a professional development model; and a conceptual framework that guides the work to support evaluation planning and implementation in schools and districts. School and district teams serve as active participants in the professional development and ultimately as formative evaluators of their own school or district-level programs by working collaboratively with evaluation experts. The CAPE framework involves the school and district staff in planning and implementing their evaluation. They are the ones deciding what evaluation questions to ask, which instruments to use, what data to collect, and how and to whom results should be reported. Initially this work is done through careful scaffolding by evaluation experts, where supports are slowly pulled away as the educators gain experience and confidence in their knowledge and skills as evaluators. Since CAPE engages all stakeholders in all stages of the evaluation, the philosophical intentions of these efforts to build capacity for formative evaluation strictly aligns with the collaborative evaluation approach. PMID- 22293533 TI - Pharmacokinetics and antiviral activity of PHX1766, a novel HCV protease inhibitor, using an accelerated Phase I study design. AB - BACKGROUND: PHX1766 is a novel HCV NS3/4 protease inhibitor with robust potency and high selectivity in replicon studies (50% maximal effective concentration 8 nM). Two clinical trials investigated the safety, tolerability, pharmacokinetics and antiviral activity of PHX1766 in healthy volunteers (HV) and chronic hepatitis C patients, by use of a dose-adaptive overlapping clinical trial design. METHODS: Two randomized, double-blind, placebo-controlled clinical trials were conducted. Single doses of PHX1766 or placebo were administered to 25 HV and six HCV genotype 1-infected patients (50 mg once daily -1,000 mg once daily, 250 mg twice daily and 100 mg of a new formulation of PHX1766 once daily). Multiple doses of PHX1766 or placebo were administered to 32 HV and seven HCV genotype 1 infected patients (50 mg once daily -800 mg twice daily). RESULTS: Oral administration of PHX1766 was safe and well tolerated at all dose levels with rapid absorption (time at which concentration maximum is reached of 1-4 h) and with mean terminal half-lives of 4-23 h. Multiple doses of PHX1766 800 mg twice daily in HCV patients produced an area under the plasma concentration-time curve from time of drug administration to the last time point with a measurable concentration after dosing accumulation ratio of 2.3. The mean maximal observed HCV RNA decline was 0.6 log(10) IU/ml in the first 24 h in the single-dose protocol and 1.5 log(10) IU/ml after 6 days of PHX1766 dosing. CONCLUSIONS: An overlapping, dose-adaptive single-dose and multiple-dose escalating design in HV and HCV-infected patients proved to be highly efficient in identifying a therapeutic dose. Although in vitro replicon studies indicated a robust HCV RNA viral decline of PHX1766, the study in HCV patients demonstrated only modest viral load reduction. PMID- 22293534 TI - Phenotypic and functional maturation of murine dendritic cells (DCs) induced by purified Glycyrrhizin (GL). AB - The aim of this study is to investigate phenotypic and functional modulation of murine dendritic cells (DCs) with use of purified Glycyrrhizin (GL). These impacts of GL on DCs both from bone marrow derived DCs and established DC cell 2.4 were assessed with conventional scanning electron microscopy (SEM), flow cytometry (FCM), transmission electron microscopy (TEM), cytochemistry assay, FITC-dextran, bio-assay and enzyme linked immunosorbent assay (ELISA). We found that the purified GL induced phenotypic maturation as evidenced by increased expression of CD86, CD40, CD80, CD83 and major histocompatibility complex II (MHC II). The functional tests showed the activity of acidic phosphatase (ACP) inside the DCs2.4 cells were down- regulated after treatment with GL (which occurs when phagocytosis of DCs2.4 cells were decreased). Finally, we proved that GL increased the production of IL-12, IL-10 and decreased the production of tumor necrosis factor alpha (TNF-alpha). These data indicated that GL could promote maturation of DCs and this adjuvant-like activity may have potential therapeutic value. It is therefore concluded that GL could exert positive modulation on murine DCs. PMID- 22293535 TI - Discrepant roles of CpG ODN on acute alcohol-induced liver injury in mice. AB - Increasing evidence suggests that the alcoholic liver injury is associated with activation of Toll-like receptors (TLRs) and the consequent over-production of inflammatory cytokines such as TNF-alpha. However, few studies have evaluated the effect of CpG ODN, a TLR9 agonist, on alcoholic liver injury. In this study, an animal model of acute alcohol-induced liver injury was established by administering the mice with alcohol at 7 g/kg intragastrically once. Using the model, 2216, an A-type CpG ODN, was found able to dramatically elevate serum ALT levels and aggravate pathological changes of liver in mice. In contrast, 2006, a B-type CpG ODN, caused elevation of serum ALT levels with no visible aggravation of liver pathological changes; YW002, a C-type CpG ODN, caused no elevation of serum ALT levels and seemed able to lessen pathological changes in the liver of the mice. Real-time RT-PCR revealed that 2216 dramatically up-regulated the expression of TLR9 and TNF-alpha and YW002 was unable to up-regulate expression of TLR9 and TNF-alpha, instead up-regulate the expression of IFN-alpha in the livers of the model mice. The data suggest that 2216 could aggravate alcohol induced liver injury by inducing the up-regulation of hepatic TLR9 and TNF-alpha and that YW002 could alleviate the pathological changes induced by acute alcohol intake by up-regulating IFN-alpha, possibly. PMID- 22293536 TI - PharmGKB summary: caffeine pathway. PMID- 22293537 TI - A genome-wide association study identifies four genetic markers for hematological toxicities in cancer patients receiving gemcitabine therapy. AB - OBJECTIVE: Genetic factors are thought to be one of the causes of individual variability in the adverse reactions observed in cancer patients who received gemcitabine therapy. However, genetic factors determining the risk of adverse reactions of gemcitabine are not fully understood. PATIENTS AND METHODS: To identify a genetic factor(s) determining the risk of gemcitabine-induced leukopenia/neutropenia, we conducted a genome-wide association study, by genotyping over 610 000 single nucleotide polymorphisms (SNPs), and a replication study in a total of 174 patients, including 54 patients with at least grade 3 leukopenia/neutropenia and 120 patients without any toxicities. RESULTS: We identified four loci possibly associated with gemcitabine-induced leukopenia/neutropenia [rs11141915 in DAPK1 on chromosome 9q21, combined P=1.27*10, odds ratio (OR)=4.10; rs1901440 on chromosome 2q12, combined P=3.11*10, OR=34.00; rs12046844 in PDE4B on chromosome 1p31, combined P=4.56*10, OR=4.13; rs11719165 on chromosome 3q29, combined P=5.98*10, OR=2.60]. When we examined the combined effects of these four SNPs, by classifying patients into four groups on the basis of the total number of risk genotypes of these four SNPs, significantly higher risks of gemcitabine-induced leukopenia/neutropenia were observed in the patients having two and three risk genotypes (P=6.25*10, OR=11.97 and P=4.13*10, OR=50.00, respectively) relative to patients with zero or one risk genotype. CONCLUSION: We identified four novel SNPs associated with gemcitabine-induced severe leukopenia/neutropenia. These SNPs might be applicable in predicting the risk of hematological toxicity in patients receiving gemcitabine therapy. PMID- 22293539 TI - Traction and fixation of four neglected fracture-subluxations of the distal interphalangeal joint. PMID- 22293538 TI - The G671V variant of MRP1/ABCC1 links doxorubicin-induced acute cardiac toxicity to disposition of the glutathione conjugate of 4-hydroxy-2-trans-nonenal. AB - OBJECTIVE: Doxorubicin-induced acute cardiotoxicity is associated with the Gly671Val (G671V; rs45511401) variant of multidrug resistance-associated protein 1 (MRP1). Doxorubicin redox cycling causes lipid peroxidation and generation of the reactive electrophile, 4-hydroxy-2-trans-nonenal (HNE). Glutathione forms conjugates with HNE, yielding an MRP1 substrate, GS-HNE, whose intracellular accumulation can cause toxicity. METHODS: We established stable HEK293 cell lines overexpressing wild-type MRP1 (HEKMRP1), G671V (HEKG671V), and R433S (HEKR433S), a variant not associated with doxorubicin-induced cardiotoxicity and investigated the sensitivity of HEKG671V cells to doxorubicin and transport capacity of G671V toward GS-HNE. RESULTS: In ATP-dependent transport studies using plasma membrane derived vesicles, the Vmax (pmol/min/mg) for GS-HNE transport was the lowest for G671V (69+/-4) and the highest for R433S (972+/-213) compared with wild-type MRP1 (416+/-22), whereas the Km values were 2.8+/-0.4, 6.0 or more, and 1.7+/-0.2 umol/l, respectively. In cells, the doxorubicin IC50 (48 h) was not different in HEKMRP1 (463 nmol/l) versus HEKR433S (645 nmol/l), but this parameter was significantly lower in HEKG671V (181 nmol/l). HEKG671V retained significantly (approximately 20%) more, whereas HEKR433S retained significantly less intracellular doxorubicin than HEKMRP1. Similarly, HEKG671V cells treated with 1.5 umol/l of doxorubicin for 24 h retained significantly more GS-HNE. In cells treated with 0.5 umol/l of doxorubicin for 48 , glutathione and glutathione disulfide levels and the glutathione/glutathione disulfide ratio were significantly decreased in HEKG671V versus HEKMRP1; these values were similar in HEKR433S versus HEKMRP1. CONCLUSION: These data suggest that decreased MRP1 dependent GS-HNE efflux contributes to increased doxorubicin toxicity in HEKG671V and potentially in individuals carrying the G671V variant. PMID- 22293540 TI - Sesamoid arthrodesis of the thumb interphalangeal joint to prevent hyperextension. PMID- 22293541 TI - Pharmacokinetics of the H(2) blocker roxatidine acetate hydrochloride in pediatric patients, in comparison with healthy adult volunteers. AB - Clinical studies were conducted to investigate the pharmacokinetics of roxatidine acetate hydrochloride capsules (ALTAT((r)) CAPSULES) in children. In a single dose pharmacokinetic (PK) study in pediatric patients aged between 6 and 14 years with acid-related diseases, 37.5 mg or 75 mg roxatidine capsules were given orally, and blood samples were collected to determine the plasma roxatidine concentrations. Meanwhile, a single-dose PK study in healthy adult volunteers was newly conducted; subjects were given 37.5 mg, 75 mg or 150 mg roxatidine capsules. Differences were present between the PK parameters in pediatric patients and those in healthy adult volunteers. However, the CL/F and Vd/F adjusted by body surface area (BSA) or body weight (BW) were comparable. A close correlation of the C(max) and AUC(0-infinity) to the dose per unit BSA (mg/m(2)) or BW (mg/kg) was also shown. In the multiple-dose study in pediatric patients, no roxatidine accumulation in plasma was observed, as was the case with a previous study in adults. These data show that the PK profile of roxatidine in pediatric patients is similar to the profile in healthy adult volunteers when adjusted by BSA or BW. PMID- 22293542 TI - Post-exposure prophylaxis for HIV infection: a clinical trial comparing lopinavir/ritonavir versus atazanavir each with zidovudine/lamivudine. AB - BACKGROUND: A clinical trial comparing the rate of discontinuation and tolerability of two post-exposure prophylaxis (PEP) regimens was performed. METHODS: A total of 255 individuals attending the emergency rooms of six hospitals for exposure to HIV and criteria to receive PEP were randomized to receive zidovudine/lamivudine plus either lopinavir/ritonavir (n=131) or atazanavir (n=124; day 0). The primary end point was the rate of PEP discontinuation before day 28 of follow-up. Secondary end points were incidence of side effects, follow-up at days 90 and 180 and rate of seroconversions. RESULTS: A total of 55 patients (29 in lopinavir/ritonavir and 26 in atazanavir arms) did not attend the first scheduled appointment (day 1) and were excluded from the analysis. The rate of discontinuation before day 28 owing to any cause was similar between groups (37/102 [36%] in lopinavir/ritonavir and 35/98 [36%] in atazanavir arms, P=0.82). Adverse events were the reason for discontinuation or switching of PEP in 33 individuals (16/102 [16%] in the lopinavir/ritonavir arm and 17/98 [17%] in the atazanavir arm, P=0.84). Adverse events were reported in 92/200 (46%) of individuals on PEP who attend at least the day 1 appointment (50/102 [49%] in the lopinavir/ritonavir arm and 42/98 [43%] in the atazanavir arm, P=0.38). There were no seroconversions. CONCLUSIONS: The rate of discontinuation of PEP before day 28 was similar with zidovudine/lamivudine plus either lopinavir/ritonavir or atazanavir. The rate of discontinuation of PEP because of adverse events was low in both arms. Almost 50% of the patients of both arms suffered side effects. New strategies are needed to improve the tolerance. PMID- 22293543 TI - Heparin serves as a natural stimulant of the inflammasome and exacerbates the symptoms of tumor necrosis factor receptor-associated periodic syndrome (TRAPS). PMID- 22293544 TI - Analysis of patterns of three-phase bone scintigraphy for patients with complex regional pain syndrome diagnosed using the proposed research criteria (the 'Budapest Criteria'). AB - BACKGROUND: Three-phase bone scintigraphy (TPBS) is an established objective diagnostic method for complex regional pain syndrome (CRPS), but its validity remains controversial. The aims of this study were: (i) to re-evaluate the diagnostic performance of TPBS, and (ii) to suggest new TPBS criteria based on the proposed research criteria for CPRS in Budapest (the 2003 Budapest research criteria). METHODS: The medical records of 228 consecutive patients, evaluated using the Budapest research criteria, were retrospectively analysed. Of these, 116 patients were included in the present study, and 69 of 116 were diagnosed to have CRPS based on these criteria. The diagnostic performance of TPBS was assessed by determining its sensitivity, specificity, and positive and negative likelihood ratios, and new criteria for TPBS were identified by pattern analysis using the Budapest research criteria. RESULTS: The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of TPBS for the diagnosis of CRPS according to the Budapest research criteria were 40.0, 76.5, 1.73, and 0.78, respectively. Furthermore, D-D-D, D-D-S, and D-D-I patterns [i.e. according to decreased (D), symmetrical (S), or increased (I) tracer uptake during Phases I, II, and III] of TPBS were found to be positively predictive for CRPS. CONCLUSIONS: The diagnostic value of a positive TPBS for CRPS is low from the view point of the Budapest research criteria. Our findings suggest that a diagnosis of CRPS using the Budapest research criteria should be considered when decreased patterns of TPBS are observed during Phases I and II. PMID- 22293545 TI - The pervasive effects of childhood sexual abuse: challenges for improving HIV prevention and treatment interventions. PMID- 22293547 TI - Analysis of a previously identified "pain-protective" haplotype and individual polymorphisms in the GCH1 gene in Africans with HIV-associated sensory neuropathy: a genetic association study. AB - We analyzed GTP cyclohydrolase 1 in symptomatic HIV-associated sensory neuropathy in Southern Africans including a "pain-protective" 3-SNP haplotype and 6 SNPs, analyzed individually and in a 6-SNP haplotype. The "pain-protective" 3-SNP haplotype and a 6-SNP haplotype containing these alleles associated with a reduced risk of pain. Another 3-SNP haplotype associated with increased presence of pain. Associations were lost after correction for age, gender, and CD4 T-cell count. Linkage disequilibrium differed between our cohort and Caucasians suggesting that these SNPs may not be ideal markers in Africans. Subsequently, the role of GTP cyclohydrolase 1 in painful HIV-associated sensory neuropathy remains possible. PMID- 22293546 TI - Long-term efficacy and safety of raltegravir, etravirine, and darunavir/ritonavir in treatment-experienced patients: week 96 results from the ANRS 139 TRIO trial. AB - Among 103 patients with multidrug-resistant HIV who initiated raltegravir, etravirine, and darunavir/ritonavir-containing regimen in the ANRS 139 TRIO trial, 100 participated in extended follow-up and continued study treatment until week 96. Among them, 87 (87%) received an optimized background therapy including either nucleoside reverse transcriptase inhibitors or enfuvirtide, they were 78 (78%) at week 96. At week 96, 88% achieved durable virologic response (<50 copies/mL). CD4 response was maintained (median change of +150 cells/mm(3)). No major toxicity was reported. This triple drug combination showed sustained efficacy and thus should be strongly considered for patients with multiclass resistant virus. PMID- 22293549 TI - Risk factors associated with inpatient hospital utilization in HIV-positive individuals and relationship to HIV care engagement. AB - BACKGROUND: Prompt linkage to HIV primary care may reduce the need for inpatient hospitalization. METHODS: Retrospective cohort study of South Carolina HIV infected individuals diagnosed from January 1986 to December 2006 who utilized 62 inpatient facilities from (January 2007 to June 2010). Suboptimal primary care engagement was defined as <2 reports of a CD4T-cell count or viral load value to surveillance in each calendar year from January 2007 to June 2010. Multivariable logistic regression explored associations of HIV primary care engagement with inpatient hospitalization after accounting for sociodemographic characteristics and disease stage. Poisson and negative binominal regression examined primary care engagement, sociodemographic characteristics, and disease stage on frequency of inpatient hospitalization and total inpatient days. RESULTS: Individuals presenting to the hospital with an AIDS-defining illness had greater risk of suboptimal HIV primary care engagement [adjusted odds ratio (aOR) = 1.58; 95% confidence interval (CI): 1.23 to 2.04] more inpatient hospitalizations (incidence rate ratio [IRR] = 1.74; 95% CI: 1.65 to 1.83) and inpatient days (IRR = 2.17; 95%CI: 2.00 to 2.36). Blacks demonstrated greater suboptimal care risk (aOR = 1.61; 95% CI: 1.15 to 2.25), more inpatient visits (IRR = 1.09; 95% CI: 1.01 to 1.17), and inpatient days (IRR = 1.21; 95% CI: 1.09 to 1.34). Medicare protected against suboptimal primary care engagement (aOR = 0.66; 95% CI: 0.46 to 0.95) but was associated with more hospitalizations (IRR = 1.09; 95% CI: 1.01 to 1.18). AIDS disease stage was associated with decreased suboptimal care risk (AIDS <= 1 year, aOR = 0.05; 95% CI: 0.02 to 0.12; AIDS > 1 year, aOR = 0.11; 95% CI: 0.06 to 0.20) but more hospitalizations (AIDS <=1 year, IRR = 1.12; 95% CI: 1.04 to 1.21; AIDS > 1 year, IRR = 1.12; 95% CI: 1.04 to 1.21) and inpatient days (AIDS <= 1 year, IRR = 1.22; 95% CI: 1.08 to 1.37; AIDS >1 year, IRR = 1.35; 95% CI: 1.21 to 1.50). CONCLUSIONS: Disease stage, race, and insurance status strongly influence HIV primary care engagement and inpatient hospitalization. Admissions may be related to general medical conditions, substance abuse, or antiretroviral therapy. PMID- 22293548 TI - Predictors of 5-year mortality in HIV-infected adults starting highly active antiretroviral therapy in Thailand. AB - OBJECTIVE: To estimate the early and long-term mortalities and associated risk factors in adults receiving highly active antiretroviral therapy (HAART) in Thailand. DESIGN: A prospective observational cohort study. METHODS: Previously untreated adults starting HAART in 2002-2009 were followed-up in 43 public hospitals. Kaplan-Meier probability of survival was estimated up to 5 years of therapy. Factors associated with early (<=6 months) and long-term (>6 months) mortalities were assessed using Cox regression analyses. RESULTS: A total of 1578 adults received HAART (74% women; median age, 33 years; CD4 cell count, 124/mL), with a median follow-up of 50 months (interquartile range, 41-66). Eighty-nine patients (6%) died (37 occurred <=6 months and 52 occurred >6 months) and 183 (12%) were lost to follow-up. Probability of survival [95% confidence interval (CI)] was 97.5% (96.7% to 98.2%) at 6 months, 96.6% (95.6% to 97.4%) at 1 year, and 93.5% (91.9% to 94.8%) at 5 years. Probability of being alive and on follow up was 80.8% (78.5% to 82.8%) at 5 years. Early mortality was associated with anemia [adjusted hazard ratio (aHR) 3.6, 95% CI: 1.7 to 7.5] and low CD4 count (aHR 1.6, 95% CI: 1.1 to 2.2 per 50 cells decrease) at treatment initiation. Long term mortality was associated with persistent anemia (aHR 4.9, 95% CI: 2.1 to 11.6), CD4 increase from baseline <50 cells per cubic millimeter (aHR 3.1, 95% CI: 1.6 to 5.7), and viral load >1000 copies per milliliter (aHR 2.8, 95% CI: 1.3 to 6.1) at 6 months of HAART; male gender; and calendar year of enrollment. CONCLUSIONS: Early mortality was associated with anemia and severe immunosuppression at initiation of therapy. Long-term mortality was associated with persistent anemia, CD4 count increase, and virological response at 6 months of therapy over baseline characteristics, highlighting the importance of laboratory monitoring. PMID- 22293550 TI - Psychometric validation of the PROQOL-HIV questionnaire, a new health-related quality of life instrument-specific to HIV disease. AB - OBJECTIVES: This study reports the psychometric validation of a new HIV/AIDS specific health-related quality of life (HRQL) questionnaire, the Patient Reported Outcomes Quality of Life-HIV. The instrument was developed simultaneously across Europe, North and South America, Africa, Asia, and Australia to assess multidimensional quality of life impairments in the era of highly active antiretroviral therapy. METHOD: A cross-sectional study was performed in 8 countries. The pilot 70-item questionnaire was co-administered with the HIV symptoms index, the EQ-5D and Medical Outcomes Study-HIV questionnaires. Demographic and biomedical data were collected. After item analysis and reduction, convergent discriminant concurrent validity and known group validity were examined. Internal consistency and reliability scores were assessed using Cronbach alpha and intraclass correlation. RESULTS: The final sample of 791 patients was composed of 64% males (median age: 41 years, HIV diagnosis = 5 years), 13.8% were treatment naive. Item reduction yielded a 43 item form surveying 8 dimensions and 1 global health item that showed good convergent and discriminant validity and reliability (98% scaling success; Cronbach alphas 0.77-0.89). Correlations with EQ-5D and Medical Outcomes Study HIV complied with concurrent validity expectations; likewise, correlations against the number of self-reported symptoms and depression showed good support for criterion validity. A test-retest study on French patients (n = 34) showed temporal stability (intraclass correlation coefficient = 0.86). Significant and meaningful differences of HRQL scores between countries were found. CONCLUSIONS: The Patient Reported Outcomes Quality of Life-HIV questionnaire is a valid and reliable instrument for assessing HRQL specific to HIV disease in different cultures and healthcare systems. PMID- 22293551 TI - Determination of optimized multidisciplinary care team for maximal antiretroviral therapy adherence. AB - OBJECTIVE: We seek to determine the optimized multidisciplinary care team (MDCT) composition for antiretroviral therapy (ART) adherence. METHODS: We analyzed all new regimen starts (n = 10,801; 7071 ART naive, 3730 ART experienced) among HIV positive patients in Kaiser Permanente California from 1996 to 2006. We measured 12-month adherence to ART (pharmacy refill methodology) and medical center specific patient exposure to HIV/infectious disease specialist (reference group), non-HIV primary care provider, clinical pharmacist, nurse case manager, non-nurse care coordinator, dietician, social worker/benefits coordinator, health educator, and mental health worker. We used recursive partitioning to ascertain potential MDCT compositions associated with maximal mean ART adherence. We then employed mixed linear regression with clustering by provider and medical center (adjusting for ART experience, age, gender, race/ethnicity, HIV risk, hepatitis C virus coinfection, ART regimen class, and calendar year) to test which potential MDCT combination identified had statistically significant association with ART adherence. RESULTS: We found maximal increase in adherence with pharmacist plus coordinator plus primary care provider combination (8.1% ART adherence difference compared with reference; 95% confidence interval: 2.7% to 13.5%). Other MDCT teams with significantly (P < 0.05) improved adherence compared with specialist only were nurse plus social worker with primary care provider (7.5%; 5.4% to 9.7%), specialist plus mental health worker (6.5%; 2.6% to 10.4%), pharmacist plus social worker plus primary care provider (5.7%; 4.1% to 7.4%), and pharmacist plus primary care provider (3.3%; 0.8% to 5.8%). Among these MDCTs, there were no significant differences in mean adherence, odds of maximal viral control, or CD4+ changes at 12 months (except pharmacist plus primary care provider). CONCLUSIONS: Various MDCTs were associated with improved adherence, including ones that did not include the HIV specialist but included primary care plus other health professionals. These findings have application to the HIV care team design. PMID- 22293552 TI - Uberon, an integrative multi-species anatomy ontology. AB - We present Uberon, an integrated cross-species ontology consisting of over 6,500 classes representing a variety of anatomical entities, organized according to traditional anatomical classification criteria. The ontology represents structures in a species-neutral way and includes extensive associations to existing species-centric anatomical ontologies, allowing integration of model organism and human data. Uberon provides a necessary bridge between anatomical structures in different taxa for cross-species inference. It uses novel methods for representing taxonomic variation, and has proved to be essential for translational phenotype analyses. Uberon is available at http://uberon.org. PMID- 22293553 TI - The deposition of iron and silver nanoparticles in graphene-polyelectrolyte brushes. AB - The high surface area of graphene nanosheets (GNs) enables them to load metal nanoparticles (NPs) for various applications such as catalysis, sensors and biomedicine. To optimize the performance, it is desired to establish an effective approach that can tune the morphology of metal nanoparticles (NPs) on GNs. We here demonstrate that GN-poly(acrylic acid) (GN/PAA) brushes can control the size and spatial distributions of iron and silver NPs. Results of Raman, Fourier transform infrared and x-ray photoelectron spectroscopy confirm the covalent bonding between PAA chains and GNs. Thermogravimetric analysis reveals a PAA grafting density of ~0.055 chain nm(-2). Transmission electron microscopy is used to study the effect of PAA chain length and precursor concentration on the morphology of the metal NPs deposited on PAA brushes and graphene oxide (GO). Short PAA brushes are found to be effective for controlling the spatial and size distributions of the NPs, resulting in small particle sizes and homogeneous distributions compared to those deposited on GO. The concentration of precursors has a limited effect on the dimension of the NPs in the brushes due to the key role that polyelectrolyte brushes play in controlling the growth of NPs. PMID- 22293554 TI - (Mis)treating the pharmacogenetic incidentalome. AB - Genome-wide screening is anticipated to accelerate the development of personalized medicine by identifying and exploiting new associations between genomic variants and drug responses. However, this goal could be undermined if care is not taken to minimize the impact of pharmacogenomic associations that turn out to have narrower implications than suggested by initial studies. PMID- 22293555 TI - 2011 FDA drug approvals. PMID- 22293557 TI - Deal watch: Abbott boosts investment in NRF2 activators for reducing oxidative stress. PMID- 22293559 TI - RuiPing Dong. Interview by Asher Mullard. PMID- 22293560 TI - The neuropathic pain market. PMID- 22293561 TI - Ruxolitinib. PMID- 22293562 TI - Medicinal chemistry: Shades of chemical beauty. PMID- 22293566 TI - Anticancer drugs: Keeping one step ahead. PMID- 22293569 TI - The critical impact of time discounting on economic incentives to overcome the antibiotic market failure. PMID- 22293567 TI - Targeting IAP proteins for therapeutic intervention in cancer. AB - Evasion of apoptosis is one of the crucial acquired capabilities used by cancer cells to fend off anticancer therapies. Inhibitor of apoptosis (IAP) proteins exert a range of biological activities that promote cancer cell survival and proliferation. X chromosome-linked IAP is a direct inhibitor of caspases - pro apoptotic executioner proteases - whereas cellular IAP proteins block the assembly of pro-apoptotic protein signalling complexes and mediate the expression of anti-apoptotic molecules. Furthermore, mutations, amplifications and chromosomal translocations of IAP genes are associated with various malignancies. Among the therapeutic strategies that have been designed to target IAP proteins, the most widely used approach is based on mimicking the IAP-binding motif of second mitochondria-derived activator of caspase (SMAC), which functions as an endogenous IAP antagonist. Alternative strategies include transcriptional repression and the use of antisense oligonucleotides. This Review provides an update on IAP protein biology as well as current and future perspectives on targeting IAP proteins for therapeutic intervention in human malignancies. PMID- 22293570 TI - Effects of a novel propionate-rich sourdough bread on appetite and food intake. AB - BACKGROUND: There is evidence linking oral propionate to a reduction in food intake, which could confer functional food properties in the fight against obesity. However, propionate is typically volatile with a pungent smell and taste and so incorporating into foods naturally, at levels acceptable to the consumer is a novel approach. SUBJECTS/METHODS: Twenty healthy, young, normal weight unrestrained eaters underwent an acute feeding study using a palatable sourdough and an identical control bread of a similar palatability, in a randomized cross over balanced design for the assessment of appetite and energy intake. RESULTS: No difference in energy intake of an ad libitum test meal, 180 min after the bread-based breakfast or in energy and macronutrient intake over the entire 24 h period was found between breads. Visual analogue scale ratings for appetite were not influenced by bread type, except the desire to eat something sweet. Elevated plasma insulin concentrations were observed following the propionate-rich sourdough breakfast (P=0.033 no effects of treatment on postprandial glycaemia were found. CONCLUSIONS: These findings suggest propionate-rich sourdough bread does not influence appetite and food intake unlike larger doses of the food preservative N-propionate. PMID- 22293568 TI - Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. AB - Studies of psychiatric disorders have traditionally focused on emotional symptoms such as depression, anxiety and hallucinations. However, poorly controlled cognitive deficits are equally prominent and severely compromise quality of life, including social and professional integration. Consequently, intensive efforts are being made to characterize the cellular and cerebral circuits underpinning cognitive function, define the nature and causes of cognitive impairment in psychiatric disorders and identify more effective treatments. Successful development will depend on rigorous validation in animal models as well as in patients, including measures of real-world cognitive functioning. This article critically discusses these issues, highlighting the challenges and opportunities for improving cognition in individuals suffering from psychiatric disorders. PMID- 22293571 TI - Genetic variation in fatty acid elongases is not associated with intermediate cardiovascular phenotypes or myocardial infarction. AB - BACKGROUND/OBJECTIVES: Elongases 2, 4 and 5, encoded by genes ELOVL2, ELOVL4 and ELOVL5, have a key role in the biosynthesis of very long chain polyunsaturated fatty acids (PUFAs). To date, few studies have investigated the associations between elongase polymorphisms and cardiovascular health. We investigated whether ELOVL polymorphisms are associated with adipose tissue fatty acids, serum lipids, inflammation and ultimately with nonfatal myocardial infarction (MI) in a Costa Rican population. SUBJECTS/METHODS: MI cases (n=1650) were matched to population based controls (n=1650) on age, sex and area of residence. Generalized linear and multiple conditional logistic regression models were used to assess the associations between seven common ELOVL polymorphisms and cardiometabolic outcomes. Analyses were replicated in The Nurses' Health Study (n=1200) and The Health Professionals Follow-Up Study (n=1295). RESULTS: Variation in ELOVL2, ELOVL4 and ELOVL5 was not associated with adipose tissue fatty acids, intermediate cardiovascular risk factors or MI. In the Costa Rica study, the number of the minor allele copies at rs2294867, located in the ELOVL5 gene, was associated with an increase in total and LDL cholesterol (adjusted P-values=0.001 and <0.0001 respectively). Additionally, the number of the minor allele copies at rs761179, also located in the ELOVL5 gene, was significantly associated with an increase in total cholesterol (adjusted P-value=0.04). However, the observed associations were not replicated in independent populations. CONCLUSION: Common genetic variants in elongases are not associated with adipose tissue fatty acids, serum lipids, biomarkers of systemic inflammation, or the risk of MI. PMID- 22293572 TI - Cochleo-vestibular clinical findings among drug resistant Tuberculosis Patients on therapy-a pilot study. AB - BACKGROUND: To investigate the Cochleo-vestibular clinical and audiometric findings in Multi and Extreme Drug Resistance(MDR and XDR) tuberculosis(TB) patients on treatment and make recommendations. METHODS: A cross-sectional study of adult MDR and XDR-TB patients was conducted in a general hospital in Cape-Town South-Africa. Ethical approval was secured and all consenting patients administered with pretested and validated questionnaire under the guidance of International Classification of Functioning, Disability and Health(ICF) Checklist version-2.1a. Audiometric evaluation included: Otoscopy, Diagnostic Audiometry and Tympanometry. The data analyses were done with SPSS version 16, Chi-square and StatCalc-7. RESULTS: Fifty-three adults, ages 18-60 (mean-33 years) comprising 26 males and 27 females participated in the study. Hospital stay duration varied from 1-18 months (mean-6 months) and all were on anti-Koch's second line drugs (regimen 2). MDR TB group were 45(85%) and XDR 8(15%). Vertigo was the most common vestibular symptoms, 24(45%) whereas, tinnitus 23(42%) and hearing loss 13(25%) were most frequent auditory complaints. Bilateral sensorineural hearing losses of varying degrees were confirmed in 23(47%).There was no association between gender and age with hearing loss [chi2 (P = 0.16, alpha = 0.05) and (p = 0.13, alpha = 0.05)]. Furthermore, MDR and XTR TB groups [20/42 Vs 3/8; Z = 0.46 and P = 0.64], showed no difference in pattern of the hearing losses. CONCLUSIONS: A multi-disciplinary close surveillance of MDR and XDR TB patients on therapy is imperative. Finally, researches into therapeutic trials on antidotes and potent safer substitutes for aminoglycosides in the management are recommended. PMID- 22293573 TI - Can compression induce demixing in amorphous solid dispersions? A case study of naproxen-PVP K25. AB - The aim of this work is to investigate the effect of compression on miscibility of naproxen (NAP)-PVP K25 solid dispersions. Solid dispersions with diverse drug/polymer compositions were compressed at various forces for uniform dwell time. Miscibility assessments were performed using mDSC, and the effect of compression on the specific interactions of NAP and PVP K25 was investigated by FTIR. The 20% (w/w) naproxen containing solid dispersion showed a single T(g) before and after compression. FTIR analysis showed the unchanged profile of this system upon compression. On the other hand, the miscibility in the compositions with 30% and 40% (w/w) naproxen is markedly affected by compression. Compression pressures from beyond 565.05 MPa induced apparent amorphous-amorphous phase separation as indicated by two characteristic T(g)s in DSC and altered IR spectral profile. The highly ductile nature of PVP promotes plastic deformation upon compression induced by the rotation of the PVP backbone with the transition of dihedral angles from low to high energy state. Segmental rotation can also be an outcome of plastic deformation that often leads to increase in structural temperature. This can have influence on miscibility resulting from weakening and/or disruption of intermolecular hydrogen bonding between drug and polymer upon compression. PMID- 22293575 TI - Leptin and the hypothalamo-pituitary-adrenal stress axis. AB - Leptin is a 16-kDa protein mainly produced and secreted by white adipose tissue and informing various brain centers via leptin receptor long and short forms about the amount of fat stored in the body. In this way leptin exerts a plethora of regulatory functions especially related to energy intake and metabolism, one of which is controlling the activity of the hypothalamo-pituitary-adrenal (HPA) stress axis. First, this review deals with the basic properties of leptin's structure and signaling at the organ, cell and molecule level, from lower vertebrates to humans but with emphasis on rodents because these have been investigated in most detail. Then, attention is given to the various interactions of adipose leptin with the HPA-axis, at the levels of the hypothalamus (especially the paraventricular nucleus), the anterior lobe of the pituitary gland (action on corticotropes) and the adrenal gland, where it releases corticosteroids needed for adequate stress adaptation. Also, possible local production and autocrine and paracrine actions of leptin at the hypothalamic and pituitary levels of the HPA-axis are being considered. Finally, a schematic model is presented showing the ways peripherally and centrally produced leptin may modulate, via the HPA-axis, stress adaptation in conjunction with the control of energy homeostasis. PMID- 22293574 TI - Sex differences in urinary biomarkers of vascular and endothelial function in HIV infected persons receiving antiretroviral therapy. AB - BACKGROUND: Cardiovascular disease (CVD) risk can be underestimated in HIV infected patients receiving antiretroviral therapy (ART). Novel CVD risk markers in this population are needed. We hypothesized that eicosanoid metabolite production is increased with metabolic complications of ART. Our objective was to determine relationships between urine eicosanoids and traditional CVD risk factors in a cohort of HIV-infected persons receiving ART. METHODS: Cross sectional analysis of 107 individuals from a prospective cohort study with urine eicosanoids (isoprostane [15-F(2t)-IsoP], prostaglandin-E metabolite [PGE-M], thromboxane metabolite [11dTxB(2)], prostacyclin metabolite [PGI-M]) determined by gas or liquid chromatography-mass spectrometry. RESULTS: 15-F(2t)-IsoP was higher (P=0.003), 11dTxB(2) tended to be higher (P=0.07) and PGE-M was lower (P=0.003) in females than in males. The overall median Framingham score was 4 (IQR 1-7). In multivariable analyses adjusting for age, CD4(+) T-cells, smoking status, non-steroidal anti-inflammatory drug use, aspirin use and body mass index (BMI), associations included: higher 15-F(2t)-IsoP with female sex (P=0.004) and current smoking (P=0.04), lower PGE-M with female sex (P=0.005) and higher BMI (P=0.03), higher 11dTxB(2) with increasing age (P=0.02) and current smoking (P=0.04), lower 11dTxB(2) with higher BMI (P=0.02), and higher PGI-M with current smoking (P=0.04). CONCLUSIONS: In this pilot study of predominantly virologically suppressed HIV-infected individuals on ART, there were sex-specific differences in urinary eicosanoids, with females having more risk-associated parameters despite a low Framingham score. Eicosanoids might be useful CVD biomarkers in ART treated, HIV-infected patients. Future studies should examine eicosanoids while assessing effects of specific ART regimens and targeted interventions on CVD outcomes. PMID- 22293577 TI - Effective RNA interference in cultured silkworm cells mediated by overexpression of Caenorhabditis elegans SID-1. AB - RNA interference (RNAi) is a conserved mechanism that catalyzes sequence-specific gene silencing and has been used for loss-of-function genetic screens in many organisms. Here, we demonstrated that the expression of Caenorhabditis elegans SID-1 (CeSID-1) could trigger effective gene silencing in the cultured silkworm cell line, BmN4 (BmN4-SID1). Soaking the BmN4-SID1 in dsRNA corresponding to endogenous target genes induced a significant decrease of the amount of mRNA or protein. A small amount of dsRNA was enough to silence the target gene in a few days. Overexpression of CeSID-1 did not affect the cell viability. Our results suggest that BmN4-SID1 can be used in many applications in silkworm cells and will become a valuable resource for gene analysis. PMID- 22293578 TI - Floating electrode transistor based on purified semiconducting carbon nanotubes for high source-drain voltage operation. AB - We report floating-electrode-based thin-film transistors (F-TFTs) based on a purified semiconducting single-walled carbon nanotube (swCNT) network for a high source-drain voltage operation. At a high source-drain voltage, a conventional swCNT-TFT exhibited poor transistor performance with a small on-off ratio, which was attributed to the reduced Schottky barrier modulation at a large bias. In the F-TFT device, an swCNT network channel was separated into a number of channels connected by floating electrodes. The F-TFTs exhibited a much higher on-off ratio than a conventional swCNT-TFT with a single channel. This work should provide an important guideline in designing swCNT-TFTs for high voltage applications such as displays. PMID- 22293579 TI - Risk factors for mortality among HIV-positive patients with and without active tuberculosis in Dar es Salaam, Tanzania. AB - BACKGROUND: The aim of this study was to describe risk factors for mortality and clinical characteristics of HIV-infected patients with and without tuberculosis (TB) coinfection. METHODS: A cohort of HIV-infected patients with CD4(+) T-cell counts of <=200 cells/MUl was recruited, consisting of 255 HIV-infected patients without active TB and 231 patients with active TB. All received a well-supervised treatment with an efavirenz-based HAART, and those coinfected with TB received appropriate anti-TB treatment. They were followed up for 48 weeks after HAART initiation. RESULTS: Common presenting symptoms in HIV-only patients were fever (36.5%), headache (34.5%), skin rash (34.5%) and weight loss (32%), while in HIV TB patients the symptoms were weight loss (58%), cough (57.6%), night sweats (44.6%) and fever (34.2%). HIV-TB patients had significantly lower body mass index, Karnofsky scores and haemoglobin levels compared to those infected with HIV only, despite similar baseline CD4(+) T-cell counts. Overall, 12 (4.7%) HIV patients developed TB and 7 (3%) HIV-TB patients had worsening of their TB symptoms during the study period. Mortality was similar in the two groups, being 10.9% (16 deaths per 100 person years) and 11.3% (17 deaths per 100 person years) in HIV-only and HIV-TB patients, respectively. Overall, more males (13.1%) died compared to females (9.6%). Predictors of mortality were presence of oral candidiasis, Kaposi's sarcoma, low Karnofsky score, and low baseline white blood cell and CD4(+) T-cell counts. CONCLUSIONS: The outcomes following well supervised treatment of HIV-TB patients are similar to those in patients with HIV alone. Predictors of mortality were those of advanced disease. PMID- 22293580 TI - Effects of functional monomers and photo-initiators on the degree of conversion of a dental adhesive. AB - Besides functional and cross-linking monomers, dental adhesives contain a photo initiator system for polymerization, thereby providing physico-mechanical strength to the adhesive-tooth interface. Few studies have investigated the effect of the functional monomer and polymerization-initiation system on the polymerization efficiency of the adhesive. Here, we tested the effect of two different functional monomers (MAC-10 vs. SR) and two photo-initiator systems, camphorquinone-amine (CQ) vs. borate (BO), on the degree of conversion (DC) of different adhesive formulations. The DC of the CQ-cured adhesive formulations was significantly affected by the MAC-10 monomer. This should be ascribed to the known inactivation of the amine co-initiator through acid-base reaction. However, the SR monomer did not decrease the DC, which could be attributed to a "gel effect" or the so-called "Trommsdorff-Norrish" phenomenon of enhanced DC with more viscous resins, and to the more favorable availability of CC double bonds. In contrast, the DC of the BO-cured adhesive formulations was not affected by any acidic monomer. It is concluded that the degree of conversion of an adhesive can be affected by the functional monomer, but this depends on the kind of photo initiator system used. As bond durability depends, among other factors, on the strength and thus degree of conversion of the adhesive, potential interaction between adhesive ingredients and the photo-initiator system definitely needs to be studied further. PMID- 22293581 TI - Enhanced angiogenesis by multiple release of platelet-rich plasma contents and basic fibroblast growth factor from gelatin hydrogels. AB - The objective of this study is to evaluate the angiogenic effects induced by biodegradable gelatin hydrogel granules incorporating mixed platelet-rich plasma (PRP) growth factor mixture (PGFM) and bioactive basic fibroblast growth factor (bFGF). The PRP was prepared by a double-spinning technique for isolating animal bloods, followed by treatment with different concentrations of calcium chloride (CaCl(2)) solution. The CaCl(2) solution treatment activated the platelets of PRP, allowing the release of various growth factors, such as platelet-derived growth factor (PDGF)-BB, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-beta(1), and epithelial growth factor (EGF). In the PRP treated with different CaCl(2) solutions, high amounts of representative platelet growth factor, PDGF-BB, VEGF, EGF, and TGF-beta(1) were detected in the CaCl(2) concentrations of 1, 2, and 4 wt.% compared with higher or lower ones. The PRP treated was impregnated into gelatin hydrogel granules freeze-dried at 37 degrees C for 1h, and then the percentage of PGFM desorbed from the gelatin hydrogel granules was evaluated. The percentages of PDGF-BB, VEGF, EGF, and TGF-beta(1) desorbed tended to decrease with decreasing CaCl(2) concentration. Taken together, the CaCl(2) concentration to activate PRP for PGFM release was fixed at 2 wt.%. In vitro release tests demonstrated that the PGFM was released from the gelatin hydrogel granules with time. For the gelatin hydrogels incorporating PGFM and bFGF, the time profile of PDGF-BB or bFGF release was in good correspondence with that of gelatin hydrogel degradation. The gelatin hydrogel granules incorporating mixed PGFM and bFGF were prepared and intramuscularly injected to a mouse leg ischemia model to evaluate the angiogenic effects in terms of histological and laser Doppler perfusion imaging examinations. As controls, hydrogel granules incorporating bFGF, PGFM, and platelet-poor plasma were used for the angiogenic evaluation. The number of blood vessels newly formed and the percentage of anti-alpha-smooth muscle actin antibody-positive cells increased around ischemic sites injected with the gelatin hydrogel granules incorporating mixed PGFM and bFGF, in marked contrast to other control groups. The blood reperfusion level of ischemic tissues was enhanced by the hydrogel granules incorporating mixed PGFM and bFGF, whereas no enhancement was observed for other groups. It is concluded that the dual-release system of PGFM and bFGF from gelatin hydrogel granules shows promise as a method to enhance angiogenic effects. PMID- 22293582 TI - Novel gradient casting method provides high-throughput assessment of blended polyester poly(lactic-co-glycolic acid) thin films for parameter optimization. AB - Pure polymer films cannot meet the diverse range of controlled release and material properties demanded for the fabrication of medical implants or other devices. Additives are added to modulate and optimize thin films for the desired qualities. To characterize the property trends that depend on additive concentration, an assay was designed which involved casting a single polyester poly(lactic-co-glycolic acid) (PLGA) film that blends a linear gradient of any PLGA-soluble additive desired. Four gradient PLGA films were produced by blending polyethylene glycol or the more hydrophobic polypropylene glycol. The films were made using a custom glass gradient maker in conjunction with a 180 cm film applicator. These films were characterized in terms of thickness, percent additive, total polymer (PLGA+additive), and controlled drug release using drug like fluorescent molecules such as coumarin 6 (COU) or fluorescein diacetate (FDAc). Material properties of elongation and modulus were also accessed. Linear gradients of additives were readily generated, with phase separation being the limiting factor. Additive concentration had a Pearson's correlation factor (R) of >0.93 with respect to the per cent total release after 30 days for all gradients characterized. Release of COU had a near zero-order release over the same time period, suggesting that coumarin analogs may be suitable for use in PLGA/polyethylene glycol or PLGA/polypropylene glycol matrices, with each having unique material properties while allowing tuneable drug release. The gradient casting method described has considerable potential in offering higher throughput for optimizing film or coating material properties for medical implants or other devices. PMID- 22293584 TI - Administration of highly purified eicosapentaenoic acid to statin-treated diabetic patients further improves vascular function. AB - We prospectively examined the additional effects of highly purified eicosapentaenoic acid (EPA) particularly on the vascular function of diabetic patients with hypercholesterolemia receiving statin therapy. We enrolled 28 patients with type 2 diabetes complicated by dyslipidemia who had been treated with statins for at least one year. The patients were randomly assigned to 2 groups: administration of statin alone (group S: n = 13) and addition of EPA to the current statin therapy (group SE: n = 15). The highly purified EPA was administered at a dose of 1,800 mg/day for 6 months. To evaluate vascular function, the duration of reactive hyperemia (DRH), which is the time required for forearm blood flow to return to the basal level after inducing reactive hyperemia, was measured using strain gauge plethysmography. There were no significant differences in the clinical background factors between the 2 groups. Low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol levels significantly decreased after 6 months only in group SE. Compared with the baseline data, no significant change in DRH was observed after 6 months in group S. By contrast, DRH was significantly prolonged after 6 months in group SE, indicating that the addition of highly purified EPA improved vascular function. Our results showed that in patients with type 2 diabetes and receiving statin therapy whose LDL-C level was less than 100 mg/dL, the addition of highly purified EPA for 6 months significantly improved vascular function. PMID- 22293583 TI - Sequential delivery of BMP-2 and IGF-1 using a chitosan gel with gelatin microspheres enhances early osteoblastic differentiation. AB - The purpose of this study was to develop and characterize a chitosan gel/gelatin microsphere (MSs) dual delivery system for sequential release of bone morphogenetic protein-2 (BMP-2) and insulin-like growth factor-1 (IGF-1) to enhance osteoblast differentiation in vitro. We made and characterized the delivery system based on its degree of cross-linking, degradation, and release kinetics. We also evaluated the cytotoxicity of the delivery system and the effect of growth factors on cell response using pre-osteoblast W-20-17 mouse bone marrow stromal cells. IGF-1 was first loaded into MSs, and then the IGF-1 containing MSs were encapsulated into the chitosan gel which contained BMP-2. Cross-linking of gelatin with glyoxal via Schiff bases significantly increased thermal stability and decreased the solubility of the MSs, leading to a significant decrease in the initial release of IGF-1. Encapsulation of the MSs into the chitosan gel generated polyelectrolyte complexes by intermolecular interactions, which further affected the release kinetics of IGF-1. This combinational delivery system provided an initial release of BMP-2 followed by a slow and sustained release of IGF-1. Significantly greater alkaline phosphatase activity was found in W-20-17 cells treated with the sequential delivery system compared with other treatments (P<0.05) after a week of culture. PMID- 22293585 TI - Association between insulin-like growth factor binding protein-2 levels and cardiovascular risk factors in Korean children. AB - Emerging evidence has indicated that insulin-like growth factor binding protein-2 (IGFBP-2) may be involved in the development of obesity and insulin resistance like IGFBP-1. The aim of this study was to measure serum IGFBP-2 levels in overweight and obese children and to compare these levels with those of controls. We also analyzed the associations between IGFBP-2 and insulin sensitivity indices and cardiovascular risk factors. 134 Korean children including 55 overweight and 59 obese subjects were enrolled. We measured anthropometric values and determined fasting serum levels of IGFBP-2, glucose, insulin, lipid profiles, and insulin sensitivity indices including the homeostatic model assessment of insulin resistance (HOMA-IR) and the Quantitative Insulin Sensitivity Check Index (QUICKI). The subjects were subgrouped based on body mass index (BMI) and pubertal stage, and association analyses between IGFBP-2 levels and measured factors were performed in each group. Serum IGFBP-2 levels in overweight or obese children were significantly lower than those of controls regardless of pubertal development. Serum IGFBP-2 levels were negatively correlated with weight, BMI, waist circumference, fasting insulin levels, and HOMA-IR but were positively correlated with QUICKI. The associations were stronger in pubertal children than those in prepubertal children. However, no association was observed between serum IGFBP-2 levels and auxological or metabolic parameters in children with normal BMIs. These results suggested that IGFBP-2 might be a promising marker for early recognition of insulin resistance, particularly in overweight or obese children, regardless of pubertal stage. PMID- 22293586 TI - Role of orexin in the central regulation of glucose and energy homeostasis. AB - Hypothalamic orexin neurons are known to regulate sleep/wake stability, feeding behavior, emotions, autonomic nerve activity, and whole-body energy metabolism. In addition, emerging evidence indicates that orexin contributes to central regulation of glucose homeostasis. Intriguingly, central administration of orexin is reported to cause blood glucose-elevating effect or blood glucose lowering effect in rodents, depending on the experimental conditions. Here we reviewed the recent reports regarding the mode and mechanism of actions of orexin on these two opposing effects, and discuss the functional significance for the maintenance of glucose homeostasis. The fact that orexin exhibits biphasic effects on autonomic nerve activity and lipolysis suggests that orexin dually regulates the glucose appearance. In fact, orexin neurons are activated not only depending on the demand for glucose but also according to a circadian rhythm in the suprachiasmatic nucleus. The excited orexin neurons appear to alter the sympathetic or parasympathetic outflow to the periphery, and modulate the glucose production and utilization. Furthermore, deficiency of orexin action, particularly reduction of orexin 2 receptor-signaling, disrupts the mechanism for protection against insulin resistance associated with aging or induced by chronic high fat feeding in mice. Taken together, hypothalamic orexin system may manage multiple tasks to coordinate the interconnection among the arousal, feeding, circadian, and glucose homeostasis pathways. PMID- 22293587 TI - Epithelial cell rests of Malassez modulate cell proliferation, differentiation and apoptosis via gap junctional communication under mechanical stretching in vitro. AB - Epithelial cell rests of Malassez (ERM) are involved in the maintenance and homeostasis of the periodontal ligament. The objective of this study was to investigate the effect of mechanical stretching on cell growth, cell death and differentiation in the ERM. Cultured porcine ERM were stretched for 24 hr in cycles of 18% elongation for 1 sec followed by 1 sec relaxation. The numbers of cells and TUNEL-positive cells were then counted. The expression of mRNAs encoding gap junction protein alpha1 (Gja1), ameloblastin, bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 4 (BMP4) and noggin were evaluated using quantitative real-time PCR. The number of cells in the stretching group was approximately 1.3-fold higher than that in the non-stretching controls at 24 hr (p<0.01). Apoptotic cells ranged from 1.9-2.5% in the stretching group at 24 hr, but were only 0.6% in the control group (p<0.01). The expression of Gja1, ameloblastin and noggin mRNAs in the stretching group was decreased at 24 hr compared with in the non-stretching group (p<0.01), whereas the expression of BMP2 and BMP4 mRNAs in the stretching group was significantly higher than that in the control group (p<0.01). Incorporation of 18 alpha-glycyrrhetinic acid (18GA, a gap junction inhibitor) promoted proliferation and apoptosis and confirmed both the increase of BMP2 and BMP4 and the decline of Gja1, ameloblastin and noggin in ERM. Thus, the ERM modulate cell proliferation and apoptosis, and inhibit differentiation by reducing expression of Gja1 under mechanical stretching. PMID- 22293588 TI - Morphological observation of process of mouse temporomandibular joint formation. AB - The aim of this study was to clarify the developmental mechanism of the temporomandibular joint (TMJ) cavity, using the relationship between Meckel's cartilage and the mandible to morphologically observe the process of TMJ formation in mouse fetuses. We investigated the involvement of apoptosis in the development of the mouse TMJ cavity. We attempted to 3-dimensionally clarify the developmental process of the mandible and Meckel's cartilage by observing the developmental process optically and reconstructing 3-dimensional images to observe 3-dimensional locations of the mandible and Meckel's cartilage. Formation of the upper joint cavity began on embryonal day 16, and a complete joint cavity was formed on embryonal day 18. Formation of the lower joint cavity began on embryonal day 18, and formation was almost completed on embryonal day 19. Meckel's cartilage adjacent to the mandible decreased with development of the mandible but was vestigial on embryonal day 19. The posterior region of Meckel's cartilage developed toward the posterior direction, and it was 3-dimensionally confirmed that the mandible and Meckel's cartilage were separated. Histological observation by the TUNEL method revealed the presence of solitary and diffuse apoptotic cells not only in the joint cavity, but also around the condyle. PMID- 22293589 TI - Longitudinal observation of developmental change in maxillary deciduous and permanent canines. AB - During the period of the growth and development of the dental arch, anterior posterior and medial-lateral changes in the maxillary deciduous and permanent canines were longitudinally studied in children. A longitudinal series of dental casts were obtained from 50 children at 2-month intervals from the completion of deciduous dentition to the stable period of permanent dentition. Subjects were divided into two groups according to the arrangement of the permanent teeth: a normal dental arch group and a crowded dental arch group. The mesial and distal points of the deciduous and permanent canines and the most prominent points on the labial and lingual contours were observed longitudinally. The results indicated that the measurement points of the deciduous canines in the normal and crowded groups moved in the anterior and lateral direction. When the amount of movement in the normal group was compared to that in the crowded group, the normal group showed greater movement than the crowded group. The permanent canines in both groups moved in the anterior and medial directions. When the amount of movement in the normal group was compared to that in the crowded group, the normal group showed more anterior movement than the crowded group, and the crowded group showed more medial movement than the normal group. When the distal point of the permanent canine was compared with the point of the deciduous canine at the exfoliation period in the normal arch group, the permanent canine was in almost the same position or was in a more anterior position than the deciduous canine. In the crowded arch group, the permanent canine tended to drift posteriorly. PMID- 22293590 TI - Osteosarcoma of maxilla with unusual image findings in child. AB - Osteosarcoma of the head and neck is relatively rare and accounts for less than 10 percent of all osteosarcomas in general. We report a case of osteosarcoma in which imaging and histopathology of the hard palate of an 11-year-old boy yielded atypical findings. An approximately 8*15mm lesion found in the center of the palate was hard and healthy in color. Subsequent biopsy resulted in a diagnosis of nonepithelial malignant tumor. No abnormalities were observed in the maxillary bone or tooth on panoramic or occlusal radiographs. Computed tomography images revealed a mass lesion approximately 7*9*9mm in size on the hard palate extending into the maxilla. The cortex of the maxilla adjacent to the lesion was unclear in parts. The internal structures were slightly inhomogeneous and its density was lower than that of muscle. On magnetic resonance images, the lesion was represented by low signal intensity on T1-weighted (T1W) images and high signal intensity on T2-weighted images with fat-suppression. The margin of the lesion was a little unclear and the internal structures were slightly inhomogeneous. The lesion was enhanced homogeneously on post-contrast T1W images with fat suppression. The histopathological diagnosis was fibrogenesis-type osteosarcoma. No findings specific to osteosarcoma such as localized enlargement of the periodontal ligament space alongside the root, cortical destruction, periosteal ossification or osteogenesis were found in this case. PMID- 22293591 TI - Effectiveness of Calvital((r)), a calcium hydroxide formulation, on persistent apical periodontitis caused by over-enlargement of apical foramen. AB - This study aimed to evaluate the effectiveness of Calvital((r)), which is a calcium hydroxide formulation, on persistent apical periodontitis caused by over enlargement of the apical foramen. The study included patients referred to the Department of General Dentistry at Tokyo Dental College Suidobashi Hospital on a diagnosis of persistent apical periodontitis at an external dental clinic. Of them, 20 showing considerable enlargement of the apical foramina were included in the study. Complete disappearance of symptoms was observed in all patients after intracanal application of Calvital((r)). We believe that this was due to effective wound-healing brought about the strong alkaline nature of this formulation. We regard Calvital((r)) as a highly effective agent for root canal treatment of teeth with persistent apical periodontitis. PMID- 22293592 TI - Two-year follow-up of treatment of intrabony periodontal defect with enamel matrix derivative. AB - The aim of this retrospective clinical study was to evaluate 2-year follow-up results following regenerative periodontal surgery for intrabony defects using enamel matrix derivative (EMD). Thirteen patients (mean age: 53 years) with a clinical diagnosis of chronic periodontitis were subjected to data analysis. A total of 25 sites with intrabony defects received regenerative therapy with EMD. Follow-up continued for a minimum of 2 years. Treatment of intrabony defects with EMD yielded a statistically significant improvement in the mean values of probing depth and gains in clinical attachment level (CAL) at 2 years compared with those at baseline (p<0.001). Sites treated with EMD demonstrated a mean CAL gain of 3.4 mm and 3.2 mm at 6 months and 2 years, respectively. No statistically significant difference in gain in CAL was found between the 6-month and 2-year results. A gain in CAL of >=3 mm from at baseline was found in 17 sites at 2 years. This gain was achieved with minimal recession of gingival margin and was sustained over a given period of time. A trend toward a progressive increase in radiopacity, suggestive of bone-fill, was observed. In summary, treatment of intrabony defects with EMD resulted in clinically favorable outcomes. The clinical improvements obtained with regenerative therapy with EMD were maintained over a period of 2 years. PMID- 22293593 TI - Surgical periodontal therapy at Tokyo Dental College Suidobashi Hospital: a statistical profile in 2010-2011. AB - The aim of the present study was to investigate the profile of surgical periodontal therapy performed at the Suidobashi Hospital of Tokyo Dental College, during the period of April 2010 through March 2011. A total of 112 periodontal surgeries in 69 patients (mean age: 51.4 years; 28 men and 41 women) were registered for the data analysis. The surgical interventions performed by 17 dentists comprised 79 cases of open flap debridement, 27 cases of periodontal regenerative therapy with enamel matrix derivative and 6 cases of periodontal plastic surgery. Eighty percent of the surgical sites were in the molar region and 41 cases had furcation involvement. In these patients, an improvement in oral hygiene status was observed prior to surgery: the mean plaque score of 45% at initial visit was significantly reduced to 31% after initial periodontal therapy (p<0.01). At sites that subsequently received open flap debridement or periodontal regenerative therapy, the mean probing depth and clinical attachment level after initial therapy was 6.4 mm and 7.6 mm, respectively. These values were significantly lower than those at initial visit (p<0.01). Lower prevalence of sites with positive bleeding on probing was observed after initial therapy. The initial periodontal therapy performed was considered to be effective in improving the periodontal condition of the sites prior to surgery. More effort, however, is indicated in improvement of patient oral hygiene status. PMID- 22293594 TI - Patterned biocatalytic films via one-step self-assembly. AB - Patterned porous films containing enzymes have been facilely prepared via a one step breath figure process, which is based on the self-assembly of horseradish peroxidase nanoparticles that show good resistance to organic solvents. The patterned biohybrid films possess robust catalytic activity. PMID- 22293595 TI - Smoke inhalation injury in a pregnant patient: a literature review of the evidence and current best practices in the setting of a classic case. AB - For smoke inhalation injury of a pregnant woman, one must treat two patients and be aware of the potential effects of carbon monoxide (CO) and cyanide (CN) poisoning on both the mother and the fetus. In a pregnant woman, the size and age of the fetus and the degree of poisoning allow for tremendous variability in the toxicity of CO and CN and their respective treatment options. The authors will review a case of a 32-year-old woman who was at 37 weeks of gestation and admitted to the Evans-Haynes Burn Center after a house fire and received hydroxocobalamin (Cyanokit) for suspected CN poisoning. In addition, a review of the literature, current guidelines, and treatment options of inhalation injury during pregnancy will be discussed. The authors will focus only on the toxic components of smoke inhalation injury rather than the mechanical components from heat and particulate damage. Literature review clearly identifies that the treatment of pregnant women with inhalation injury remains a controversial subject. The use of hydroxocobalamin (Cyanokit) as a treatment modality for potential CN poisoning in a pregnant patient has not been reported in the literature. Animal studies have shown that combined CO and CN poisoning are more lethal than either one alone and at lower concentrations. Due to the synergistic effects of CO and CN, and because these two toxins concentrate at even higher levels in the fetus than the mother, the authors will clarify the urgent seriousness of prompt administration of hydroxocobalamin in a pregnant patient with suspected smoke inhalation injury. This case review details the treatment of a 32-year-old woman who was at 36 weeks of gestation on admission to the Evans Haynes Burn Center. The authors will report her injuries and the course of treatment. Although burned and presenting with concomitant smoke inhalation injury, both the woman and her child fared well with no significant complications due to the smoke inhalation at 6 months of follow-up. Smoke inhaled from modern structural fires potentially contains both CN and CO gases. This makes the prompt recognition of this injury and selection of appropriate therapy an emergent priority. In October 2010, the Food and Drug Administration approved hydroxocobalamin for use in pregnant patients in the acute setting when CN toxicity is suspected. Because CO and CN have additive effects when both are present in the body, the prompt administration of hydroxocobalamin not only eliminates the effects of CN but also potentially attenuates its synergistic effects on CO. It is only through a better understanding of the details of smoke inhalation injury, the current treatment options, and the considerations regarding their use that new research and strong guidelines can be developed to better serve our patients. PMID- 22293597 TI - Role of focal adhesion kinase in lung remodeling of endotoxemic rats. AB - Despite significant advances in the care of critically ill patients, acute lung injury continues to be a complex problem with high mortality. The present study was designed to characterize early lipopolysaccharide (LPS)-induced pulmonary injury and small interfering RNA targeting focal adhesion kinase (FAK) as a possible therapeutic tool in the septic lung remodeling process. Male Wistar rats were assigned into endotoxemic group and control group. Total collagen deposition was performed 8, 16, and 24 h after LPS injection. Focal adhesion kinase expression, interstitial and vascular collagen deposition, and pulmonary mechanics were analyzed at 24 h. Intravenous injection of small interfering RNA targeting FAK was used to silence expression of the kinase in pulmonary tissue. Focal adhesion kinase, total collagen deposition, and pulmonary mechanics showed increased in LPS group. Types I, III, and V collagen showed increase in pulmonary parenchyma, but only type V increased in vessels 24 h after LPS injection. Focal adhesion kinase silencing prevented lung remodeling in pulmonary parenchyma at 24 h. In conclusion, LPS induced a precocious and important lung remodeling. There was fibrotic response in the lung characterized by increased amount in total and specific-type collagen. These data may explain the frequent clinical presentation during sepsis of reduced lung compliance, oxygen diffusion, and pulmonary hypertension. The fact that FAK silencing was protective against lung collagen deposition underscores the therapeutic potential of FAK targeting by small interfering RNA. PMID- 22293596 TI - Innate immune response to pulmonary contusion: identification of cell type specific inflammatory responses. AB - Lung injury from pulmonary contusion is a common traumatic injury, predominantly seen after blunt chest trauma, such as in vehicular accidents. The local and systemic inflammatory response to injury includes activation of innate immune receptors, elaboration of a variety of inflammatory mediators, and recruitment of inflammatory cells to the injured lung. Using a mouse model of pulmonary contusion, we had previously shown that innate immune Toll-like receptors 2 and 4 (TLR2 and TLR4) mediate the inflammatory response to lung injury. In this study, we used chimeric mice generated by adoptive bone marrow transfer between TLR2 or TLR4 and wild-type mice. We found that, in the lung, both bone marrow-derived and nonmyeloid cells contribute to TLR-dependent inflammatory responses after injury in a cell type-specific manner. We also show a novel TLR2-dependent injury mechanism that is associated with enhanced airway epithelial cell apoptosis and increased pulmonary FasL and Fas expression in the lungs from injured mice. Thus, in addition to cardiopulmonary physiological dysfunction, cell type-specific TLR and their differential response to injury may provide novel specific targets for management of patients with pulmonary contusion. PMID- 22293598 TI - Persistence of elevated plasma CXCL8 concentrations following red blood cell transfusion in a trauma cohort. AB - Red blood cell (RBC) transfusion is associated with alterations in systemic concentrations of IL-8/CXCL8 functional homologs in a murine model. Whether RBC transfusion alters systemic neutrophil chemokine concentrations in individuals sustaining traumatic injury is not known. We conducted a retrospective, single center study of severely injured trauma patients presenting within 12 h of injury with a base deficit greater than 6 and hypotension in the field. Plasma concentrations of 25 chemokines, cytokines, and growth factors were obtained from both transfused (n = 22) and nontransfused (n = 33) groups in the first 48 h following admission. The transfused group (mean RBC units, 2.7 [SD, 1.7]) tended to be older (49.9 [SD, 21.1] vs. 40.4 [SD, 19.9] years, P = 0.10), with a higher percentage of females (40.9% vs. 18.2%, P = 0.06) and a higher Injury Severity Score (27.1 [SD, 12.7] vs. 21.4 [SD, 10.2], P = 0.07). In univariate and multivariate analyses, transfusion was associated with increased hospital and intensive care unit length of stay but not ventilator-free days. Plasma CXCL8 concentrations were higher in the transfused (84 [SD, 88] pg/mL) than the nontransfused group (31 [SD, 21] pg/mL, P = 0.003). Using a linear prediction model to calculate bioanalyte concentrations standardized for age, sex, Injury Severity Score, and admission SBP, we observed that CXCL8 concentrations diverged within 12 h following injury, with the transfused group showing persistently elevated CXCL8 concentrations by contrast to the decay observed in the nontransfused group. Other bioanalytes showed no differences across time. Red blood cell transfusion is associated with persistently elevated neutrophil chemokine CXCL8 concentrations following traumatic injury. PMID- 22293599 TI - The role of cyclosporine in the treatment of myocardial reperfusion injury. AB - Myocardial injury in adult, pediatric, and newborn patients is a leading cause of mortality and morbidity. Although the underlying etiologies are different among patient populations, the sequence of initial ischemic-hypoxic injury followed by secondary myocardial reperfusion injury is relatively consistent. Overall infarct size is important because it is believed to be a key determinant of mortality. The detrimental effects of myocardial reperfusion have been proposed to be at least partially related to the formation of mitochondrial permeability transition pore (MPTP). The MPTP is a nonspecific pore, which forms during myocardial reperfusion and allows the release of apoptotic signaling molecules and may also lead to cellular necrosis. Cyclosporine A has been shown to be a potent inhibitor of the MPTP, leading to its study as a potential treatment to limit myocardial reperfusion injury. Multiple adult animal models have demonstrated the protective effects of cyclosporine in ischemia-reperfusion. A recent human pilot clinical trial also reported reduced myocardial injury and infarct size in patients treated with cyclosporine intravenously before percutaneous coronary intervention for ST-elevation myocardial infarction. Despite the paucity of evidence of cyclosporine A demonstrating myocardial protection in pediatric and newborn patients, the existing animal experimental results are promising. PMID- 22293600 TI - Role of macrophages in mobilization of hematopoietic progenitor cells from bone marrow after hemorrhagic shock. AB - The release of hematopoietic progenitor cells (HPCs) from bone marrow (BM) is under tight homeostatic control. Under stress conditions, HPCs migrate from BM and egress into circulation to participate in immune response, wound repair, or tissue regeneration. Hemorrhagic shock with resuscitation (HS/R), resulting from severe trauma and major surgery, promotes HPC mobilization from BM, which, in turn, affects post-HS immune responses. In this study, we investigated the mechanism of HS/R regulation of HPC mobilization from BM. Using a mouse HS/R model, we demonstrate that the endogenous alarmin molecule high-mobility group box 1 mediates HS/R-induced granulocyte colony-stimulating factor secretion from macrophages (Mphi in a RAGE [receptor for advanced glycation end products] signaling-dependent manner. Secreted granulocyte colony-stimulating factor, in turn, induces HPC egress from BM. We also show that activation of beta-adrenergic receptors on Mphi by catecholamine mediates the HS/R-induced release of high mobility group box 1. These data indicate that HS/R, a global ischemia reperfusion stimulus, regulates HPC mobilization through a series of interacting pathways that include neuroendocrine and innate immune systems, in which Mphi play a central role. PMID- 22293601 TI - Diffusion of rhodamine B and bovine serum albumin in fibrin gels seeded with primary endothelial cells. AB - Scaffolds with adequate mass transport properties are needed in many tissue engineering applications. Fibrin is considered a good biological material to fabricate such scaffolds. However, very little is known about mass transport in fibrin. Therefore, a method based on the analysis of fluorescence intensity for measuring the apparent diffusion coefficient of rhodamine B and fluorescein labelled bovine serum albumin (FITC-BSA) is described. The experiments are performed in fibrin gels with and without human umbilical vein endothelial cells (HUVEC). The apparent diffusion coefficients of rhodamine B and FITC-BSA in fibrin (fibrinogen concentration of 4 mg/mL) with different cell densities are reported. A LIVE/DEAD((r)) assay is performed to confirm the viability of HUVEC seeded at high densities. Diffusion coefficients for rhodamine B remain more or less constant up to 5*10(5) cells/mL and correlate well with literature values measured by other methods in water systems. This indicates that the presence of HUVEC in the fibrin gels (up to 5*10(5) cells/mL) has almost no effect on the diffusion coefficients. Higher cell densities (>5*10(5) cells/mL) result in a decrease of the diffusion coefficients. Diffusion coefficients of rhodamine B and FITC-BSA obtained by this method agree with diffusion coefficients in water predicted by the Stokes-Einstein equation. The experimental design used in this study can be applied to measure diffusion coefficients in different types of gels seeded or not with living cells. PMID- 22293602 TI - Solid lipid nanoparticles (SLN)--based hydrogels as potential carriers for oral transmucosal delivery of risperidone: preparation and characterization studies. AB - Two different solid lipid nanoparticles (SLN)-based hydrogels (HGs) formulations were developed as potential mucoadhesive systems for risperidone (RISP) oral transmucosal delivery. The suitability of the prepared semi-solid formulations for application on oral mucosa was assessed by means of rheological and textural analysis, during 30 days. Plastic flows with thixotropy and high adhesiveness were obtained for all the tested systems, which predict their success for the oral transmucosal application proposed. The SLN remained within the colloidal range after HGs preparation. However, after 30 days of storage, a particle size increase was detected in one type of the HGs formulations. In vitro drug release studies revealed a more pronounced RISP release after SLN hydrogel entrapment, when compared to the dispersions alone. In addition, a pH-dependent release was observed as well. The predicted in vivo RISP release mechanism was Fickian diffusion alone or combined with erosion. PMID- 22293603 TI - NBC update: The addition of viral and fungal databases to the Naive Bayes classification tool. AB - BACKGROUND: Classifying the fungal and viral content of a sample is an important component of analyzing microbial communities in environmental media. Therefore, a method to classify any fragment from these organisms' DNA should be implemented. RESULTS: We update the naive Bayes classification (NBC) tool to classify reads originating from viral and fungal organisms. NBC classifies a fungal dataset similarly to Basic Local Alignment Search Tool (BLAST) and the Ribosomal Database Project (RDP) classifier. We also show NBC's similarities and differences to RDP on a fungal large subunit (LSU) ribosomal DNA dataset. For viruses in the training database, strain classification accuracy is 98%, while for those reads originating from sequences not in the database, the order-level accuracy is 78%, where order indicates the taxonomic level in the tree of life. CONCLUSIONS: In addition to being competitive to other classifiers available, NBC has the potential to handle reads originating from any location in the genome. We recommend using the Bacteria/Archaea, Fungal, and Virus databases separately due to algorithmic biases towards long genomes. The tool is publicly available at: http://nbc.ece.drexel.edu. PMID- 22293605 TI - Neuroprotection by urokinase plasminogen activator in the hippocampus. AB - Tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA), which are both used for thrombolytic treatment of acute ischemic stroke, are serine proteases that convert plasminogen to active plasmin. Although recent experimental evidences have raised controversy about the neurotoxic versus neuroprotective roles of tPA in acute brain injury, uPA remains unexplored in this context. In this study, we evaluated the effect of uPA on neuronal death in the hippocampus of mice after kainate-induced seizures. In the normal brain, uPA was localized to both nuclei and cytosol of neurons. Following severe kainate induced seizures, uPA completely disappeared in degenerating neurons, whereas uPA expressing astrocytes substantially increased, suggesting reactive astrogliosis. uPA-knockout mice were more vulnerable to kainate-induced neuronal death than wild-type mice. Consistent with this, inhibition of uPA by intracerebral injection of the uPA inhibitor UK122 increased the level of neuronal death. In contrast, prior administration of recombinant uPA significantly attenuated neuronal death. Collectively, these results indicate that uPA renders neurons resistant to kainate-induced excitotoxicity. Moreover, recombinant uPA suppressed cell death in primary cultures of hippocampal neurons exposed to H2O2, zinc, or various excitotoxins, suggesting that uPA protects against neuronal injuries mediated by the glutamate receptor, or by oxidation- or zinc-induced death signaling pathways. Considering that tPA may facilitate neurodegeneration in acute brain injury, we suggest that uPA, as a neuroprotectant, might be beneficial for the treatment of acute brain injuries such as ischemic stroke. PMID- 22293606 TI - DYRK1A: a master regulatory protein controlling brain growth. AB - Copy number variation in a small region of chromosome 21 containing DYRK1A produces morphological and cognitive alterations in human. In mouse models, haploinsufficiency results in microcephaly, and a human DYRK1A gain-of-function model (three alleles) exhibits increased brain volume. To investigate these developmental aspects, we used a murine BAC clone containing the entire gene to construct an overexpression model driven by endogenous regulatory sequences. We compared this new model to two other mouse models with three copies of Dyrk1a, YACtgDyrk1a and Ts65Dn, as well as the loss-of-function model with one copy (Dyrk1a(+/-)). Growth, viability, brain weight, and brain volume depended strongly upon gene copy number. Brain region-specific variations observed in gain of-function models mirror their counterparts in the loss-of-function model. Some variations, such as increased volume of the superior colliculus and ventricles, were observed in both the BAC transgenic and Ts65Dn mice. Using unbiased stereology we found that, in the cortex, neuron density is inversely related to Dyrk1a copy number but, in thalamic nuclei, neuron density is directly related to copy number. In addition, six genes involved either in cell division (Ccnd1 and pAkt) or in neuronal machinery (Gap43, Map2, Syp, Snap25) were regulated by Dyrk1a throughout development, from birth to adult. These results imply that Dyrk1a expression alters different cellular processes during brain development. Dyrk1a, then, has two roles in the development process: shaping the brain and controlling the structure of neuronal components. PMID- 22293608 TI - Upstream at the watershed moment. PMID- 22293607 TI - Predicted effect of direct acting antivirals in the current HIV-HCV-coinfected population in Spain. AB - BACKGROUND: Direct acting antivirals (DAAs) against HCV are eagerly awaited for HIV-HCV-coinfected individuals. However, the activity of first generation drugs is limited to HCV genotype 1 and is lower in cirrhotics, subtype 1a infections, prior interferon (IFN)-alpha exposure or unfavourable IL28B alleles. Herein, we report the current profile of HIV-HCV-coinfected patients at our institution in an attempt to predict the effect of DAAs. METHODS: All HIV-HCV-coinfected patients seen at our HIV outpatient clinic in 2011 were identified. Information on serum HCV RNA, HCV genotype/subtype, plasma HIV RNA, prior IFN-alpha experience, liver fibrosis staging and IL28B alleles was recorded. RESULTS: A total of 424 HIV-HCV-coinfected patients were identified, of whom 174 (41%) were IFN-alpha-experienced. Mean serum HCV RNA was 6 log IU/ml. HCV genotype/subtype distribution was 166 (39.1%) G1a, 93 (22%) G1b, 85 (20%) G4, 49 (11.5%) G3 and 1 (<1%) G2, and 30 (7%) were unclassified. Of note, 56% of G1a were prior IFN-alpha experienced patients. Overall, 37% had advanced liver fibrosis (Metavir score estimates F3-F4). Finally, 70% harboured unfavourable IL28B alleles. CONCLUSIONS: The current profile of HIV-HCV-coinfected patients in Spain is dominated by particularly difficult-to-treat individuals, such as those infected with G1a or G4 (59%), advanced liver fibrosis (37%) and unfavourable IL28B alleles (70%). A wide use of prior anti-HCV therapy in our region most likely has resulted in hepatitis C cure of more IFN-alpha susceptible individuals, with accumulation of a more refractory treatment population. Thus, the use of DAAs in HIV-HCV coinfected patients will require particular expertise and their benefit might be lower than expected. PMID- 22293609 TI - The association of ownership type with job insecurity and worry about job stability: the moderating effects of fair management, positive leadership, and employment type. AB - This study examined whether the ownership type is associated with job insecurity and worry about job stability and whether the type of employment contract, positive leadership, and fair management moderated these associations. Survey data from 1249 Finnish female elderly care staff aged 18 to 69 years were used. Job insecurity and worry about job stability were highest in not-for-profit sheltered homes. However, positive leadership and fair management were able to mitigate this insecurity and worry. Job insecurity was highest among fixed-term employees in public sheltered homes or not-for-profit nursing homes. Thus, promoting good leadership and fair management would be of importance. PMID- 22293610 TI - Rates and predictors of depression in adoptive mothers: moving toward theory. AB - There are approximately 1.8 million adopted children living in the United States. Adoptive parents may experience depressive symptoms and put their children at risk for negative outcomes. The results of this study describe the rates of depression in 300 adoptive mothers and associations with hypothesized explanatory variables, which predict approximately half of the variance in maternal depressive symptoms: expectations of themselves as mothers, the child, and family and friends; feeling of rest; past and present psychiatric difficulties (self esteem, history of depression); and interpersonal variables (bonding, marital satisfaction, perceived support). These findings are useful in planning effective interventions to mitigate depressive symptoms. PMID- 22293611 TI - The influence of the culture of care on informal caregivers' experiences. AB - The environment of care can have a profound impact on caregiving experiences of families caring for loved ones with a life-limiting illness. Care is often delivered through disease-specific specialty clinics that are shaped by the illness trajectory. In this study, the following 3 distinct cultures of care were identified: interdisciplinary, provider dominant, and cooperative network. Each of these cultures was found to express unique values and beliefs through 5 key characteristics: acknowledgment of the certainty of death, role of the formal caregiver, perception of the patient system, focus of the patient visit across the trajectory, and continuum of care across the trajectory. PMID- 22293612 TI - Understanding situation awareness in nursing work: a hybrid concept analysis. AB - Eighty percent of medical error are attributed to human factors. Human factors experts suggest the least explored factor in patient errors is attention, specifically, situation awareness. The purpose of this article was to analyze the concept of situation awareness using a hybrid concept analysis. The experience of situation awareness among nurses was elicited during the fieldwork phase through semistructured interviews. Content and relational analyses yielded 9 themes: perception, comprehension, projection, knowledge and expertise, cognitive overload, interruption management, task management, instantaneous learning, and cognitive stacking. A conceptual definition of situation awareness emerged along with recommendations for application in nursing. PMID- 22293613 TI - Exploration of parental smokers' experience, perceptions, and family's influences on their smoking in the presence of children. AB - The purpose of this study was to explore parents' experience and perceptions of smoking in the presence of children. Findings regarding patterns of parents' smoking in the presence of children were situation specific. When thinking of smoking with children around, parents engaged in a process of weighing the importance of the need to smoke and adverse effects from exposure to environmental tobacco smoke, a consideration based mostly on their experience. A pattern of correspondence was identified between family's level of concern and promoting change among smokers. Many strategies participants used to prevent children's environmental tobacco smoke exposure were relatively ineffective and needed to be addressed. PMID- 22293614 TI - Development: NUP210 takes cell fate decisions. PMID- 22293615 TI - Metabolism: Keeping fit with autophagy. PMID- 22293616 TI - RimJ-mediated context-dependent N-terminal acetylation of the recombinant Z domain protein in Escherichia coli. AB - N-terminal acetylation of the recombinant Z-domain protein depends on E. coli strains, expression vectors and amino acid residues near the N-terminus, and is enhanced by a high cellular level of RimJ. PMID- 22293617 TI - The impact of plant-pathogen studies on medicinal drug discovery. AB - The pharmaceutical industry is reliant on a constant supply of new chemical entities and molecular targets for disease intervention. In this tutorial review, we want to illustrate that basic research studies on the biological function of natural products involved in plant-pathogen interactions can serve as an inspiring source for the identification of new bioactive entities as well as of strategies on how to achieve small molecule manipulation of biological systems. An application of findings from plant-pathogen interaction studies might therefore display a significant impact on drug discovery. PMID- 22293618 TI - Mid-term results of the Lupiae technique in patients with De Bakey Type I acute aortic dissection. AB - OBJECTIVES: The late persistence of a patent and dilated false lumen into the thoracic aorta is associated to higher re-operation rates and to a worse prognosis after the surgical repair of De Bakey Type I acute aortic dissection (TIAAD). We present the mid-term results of a hybrid, two-stage technique for TIAAD aimed to reduce the risk of late expansion of the residual false lumen. METHODS: From May 2005 to January 2011, 49 patients with TIAAD were treated with the Lupiae technique. During the emergency operation, a Vascutek LupiaeTM, a multi-branched Dacron prosthesis, was implanted to replace the ascending aorta, the aortic arch and to reroute the origin of the epiaortic vessels. The debranching of the aortic arch creates a long and stable Dacron landing zone on the ascending aorta suitable for further endovascular interventions. Postoperatively, 34 patients with a patent or partially thrombosed false lumen > 22 mm or a diameter of the descending aorta > 46 mm underwent the implant endovascular stentgrafts into the descending aorta. RESULTS: Three patients died after the first procedure. One patient died after the endovascular stage. No patient experienced paraplegia or stroke. The 6-year follow-up survival was 90 +/ 4%. The obliteration of the false lumen was obtained in 94% of the patients. CONCLUSIONS: In patients with TIAAD, the debranching of the aortic arch with the Lupiae technique can be safely performed. This technique creates a long and stable landing zone that can be easily used for the deployment of endovascular stentgrafts in case of distal false lumen expansion. PMID- 22293619 TI - A successful case of a surgical resection for primary lung cancer with polypoid growth in the main pulmonary artery. PMID- 22293620 TI - PREVAIL TRANSAPICAL: multicentre trial of transcatheter aortic valve implantation using the newly designed bioprosthesis (SAPIEN-XT) and delivery system (ASCENDRA II). AB - OBJECTIVES: Transapical (TA) aortic valve implantation (AVI) has evolved as an alternative procedure for high-risk patients. We evaluated the second-generation SAPIEN XTTM prosthesis in a prospective multicentre clinical trial. METHODS: A total of 150 patients (age: 81.6 +/- 5.8 years; 40.7% female) were included. Prosthetic valves (diameter: 23 mm (n = 36), 26 mm (n = 57) and 29 mm (n = 57)) were implanted. The ASCENDRA-IITM modified delivery system was used in the smaller sizes. Mean logistic EuroSCORE was 24.3 +/- 7.0%, and mean STS score 7.5 +/- 4.4%. All patients gave written informed consent. RESULTS: Off-pump AVI was performed using femoral arterial and venous access wires as a safety net. All but two patients received TA-AVI, as planned. The 29-mm valve showed similar function as the values of two other diameters did. Three patients (2%) required temporary cardiopulmonary bypass support. Postoperative complications included renal failure requiring long-term dialysis in four, bleeding requiring rethoracotomy in four, respiratory complication requiring reintubation in eight and sepsis in four patients, respectively. Thirty-day mortality was 13 (8.7%) for the total cohort and 2/57 (3.5%) for patients receiving the 29-mm valve, respectively. Echocardiography at discharge showed none or trivial aortic incompetence (AI) in 71% and mild-AI in 22% of the patients. Post-implantation AI was predominantly paravalvular and >= 2+ in 7% of patients. One patient required reoperation for AI within 30 days. CONCLUSIONS: The PREVAIL TA multicentre trial demonstrates good functionality and good outcomes for TA-AVI, using the SAPIEN XTTM prosthesis and its second-generation ASCENDRA-IITM delivery system, as well successful introduction of the 29-mm SAPIEN XTTM valve for the benefit of high-risk elderly patients. PMID- 22293624 TI - Core-shell multi-quantum wells in ZnO/ZnMgO nanowires with high optical efficiency at room temperature. AB - Nanowire-based light-emitting devices require multi-quantum well heterostructures with high room temperature optical efficiencies. We demonstrate that such efficiencies can be attained through the use of ZnO/Zn((1-x))Mg(x)O core-shell quantum well heterostructures grown by metal organic vapor phase epitaxy. Varying the barrier Mg concentration from x = 0.15 to 0.3 leads to the formation of misfit induced dislocations in the multi-quantum wells. Correlatively, temperature dependent photoluminescence reveals that the radial well luminescence intensity decreases much less rapidly with increasing temperature for the lower Mg concentration. Indeed, about 54% of the 10 K intensity is retained at room temperature with x = 0.15, against 1% with x = 0.30. These results open the way to the realization of high optical efficiency nanowire-based light-emitting diodes. PMID- 22293625 TI - Induction of remission results in spontaneous enhancement of anti-tumor cytotoxic T-lymphocyte activity in dogs with B cell lymphoma. AB - Characterization of the tumor microenvironment, particularly the immune cells that infiltrate tumors, provides important predictive and prognostic information in humans with lymphoma and other types of cancer. Tumor associated T lymphocytes have not been previously described in dogs with lymphoma. Therefore, we investigated the phenotype and function of T cells in the lymph nodes of dogs with B cell Non-Hodgkin's lymphoma (NHL), as well as the function of T cells in circulation of these dogs. We found that CD4+ and CD8+ T lymphocytes were few in number and minimally responsive to mitogenic stimuli compared to T cells in lymph nodes of normal dogs. Additionally, regulatory T cells (Treg) were significantly increased in tumor tissues compared to lymph nodes of healthy dogs. To better understand cell mediated antitumor immune responses we developed a non radioactive assay to measure cytotoxic T lymphocyte (CTL) mediated killing of autologous tumor cells. Using this assay, we found that spontaneous CTL activity in the blood of dogs with lymphoma improved significantly following induction of tumor remission using doxorubicin. Coincident with the improvement in CTL activity, circulating Treg numbers were significantly decreased compared to pretreatment levels. We conclude from these studies that CTL activity in dogs with lymphoma can be significantly improved following induction of tumor remission using chemotherapy, as assessed using a new non-radioactive CTL assay. PMID- 22293626 TI - Evaluation of a manual DNA extraction protocol and an isothermal amplification assay for detecting HIV-1 DNA from dried blood spots for use in resource-limited settings. AB - BACKGROUND: In resource-limited settings (RLS) dried blood spots (DBS) are collected on infants and transported through provincial laboratories to a central facility where HIV-1 DNA PCR testing is performed using specialized equipment. Implementing a simpler approach not requiring such equipment or skilled personnel could allow the more numerous provincial laboratories to offer testing, improving turn-around-time to identify and treat infected infants sooner. OBJECTIVES: Assess performances of a manual DNA extraction method and helicase-dependent amplification (HDA) assay for detecting HIV-1 DNA from DBS. STUDY DESIGN: 60 HIV 1 infected adults were enrolled, blood samples taken and DBS made. DBS extracts were assessed for DNA concentration and beta globin amplification using PCR and melt-curve analysis. These same extracts were then tested for HIV-1 DNA using HDA and compared to results generated by PCR and pyrosequencing. Finally, HDA limit of detection (LOD) studies were performed using DBS extracts prepared with known numbers of 8E5 cells. RESULTS: The manual extraction protocol consistently yielded high concentrations of amplifiable DNA from DBS. LOD assessment demonstrated HDA detected ~470 copies/ml of HIV-1 DNA extracts in 4/4 replicates. No statistical difference was found using the McNemar's test when comparing HDA to PCR for detecting HIV-1 DNA from DBS. CONCLUSIONS: Using just a magnet, heat block and pipettes, the manual extraction protocol and HDA assay detected HIV-1 DNA from DBS at levels that would be useful for early infant diagnosis. Next steps will include assessing HDA for non-B HIV-1 subtypes recognition and comparison to Roche HIV-1 DNA v1.5 PCR assay. PMID- 22293627 TI - Prevalence of antibodies and RNA genome of hepatitis E virus in a cohort of French immunocompromised. AB - BACKGROUND: Recently, cases of chronic hepatitis E have been identified in immunocompromised patients. OBJECTIVES: To evaluate the prevalence of anti-HEV IgG antibodies and the persistence of HEV-RNA in sera of immunocompromised patients with regular follow-up at Saint-Louis Hospital in Paris, France. STUDY DESIGN: 307 samples collected from 261 HIV-infected patients and 46 kidney transplant (KT)-patients were retrospectively tested for the presence of the following hepatitis E virus (HEV) infection markers: anti-HEV IgM antibodies, anti-HEV IgG antibodies, anti-HEV IgG avidity index, and HEV-RNA. RESULTS: Anti HEV IgG positive serology was found in 4 HIV-infected patients (1.5%) and 3 KT patients (6.5%), leading to an overall seroprevalence of 2.3%. HEV-RNA detection was not observed among 55 HIV-patients at higher risk of chronic HEV (<200 CD4 cells/mm(3), elevated alanine aminotransferase (ALT) levels, and/or positive anti HEV antibodies) and among 44 KT-patients. None of the seven patients had anti-HEV IgM antibodies, thereby excluding any acute infection. The IgG avidity index confirmed past HEV infection among tested patients. CONCLUSIONS: The low seroprevalence observed in the Paris region does not warrant a systematic evaluation of HEV infection in immunocompromised patients. However, HEV infection must be examined as a possibility if unexplained increases in ALT should occur and after more common viral hepatitis infections are excluded. PMID- 22293628 TI - Levels of fibrinogen and thromboelastometry fibrin polymerisation following treatment with desmopressin (DDAVP). PMID- 22293629 TI - Measurement of antibodies to pneumococcal, meningococcal and haemophilus polysaccharides, and tetanus and diphtheria toxoids using a 19-plexed assay. AB - The measurement of antibody responses to vaccination is useful in the assessment of immune status in suspected immune deficiency. Previous reliance on enzyme linked immunoabsorbent assays (ELISA) has been cumbersome, time-consuming and expensive. The availability of flow cytometry systems has led to the development of multiplexed assays enabling simultaneous measurement of antibodies to several antigens. We optimized a flow cytometric bead-based assay to measure IgG and IgM concentrations in serum to 19 antigens contained in groups of bacterial subunit vaccines: pneumococcal vaccines, meningococcal vaccines, Haemophilus influenzae b (Hib), and tetanus and diphtheria toxoid vaccines. 89-SF was employed as the standard serum. The assay was used to determine specific antibody levels in serum from 193 healthy adult donors. IgG and pneumococcal IgM antibody concentrations were measurable across 3 log10 ranges encompassing the threshold protective IgG antibody levels for each antigen. There was little interference between antibody measurements by the 19-plexed assay compared with monoplexed assays, and a lack of cross-reactive IgG antibody, but evidence for cross-reacting IgM antibody for 3/19 pneumococcal antigens. 90th centile values for 15/19 IgG concentrations and 12/12 IgM concentrations of the 193 adult sera were within these ranges and percentages of sera containing protective IgG antibody levels varied from 4% to 95% depending on antigen. This multiplexed assay can simultaneously measure antibody levels to 19 bacterial vaccine antigens. It is suitable for use in standard clinical practice to assess the in vivo immune response to test vaccinations and measure absolute antibody levels to these antigens. PMID- 22293632 TI - Transitions. PMID- 22293630 TI - A hexane fraction of American ginseng suppresses mouse colitis and associated colon cancer: anti-inflammatory and proapoptotic mechanisms. AB - Ulcerative colitis is a chronic inflammatory condition associated with a high colon cancer risk. We have previously reported that American ginseng extract significantly reduced the inflammatory parameters of chemically induced colitis. The aim of this study was to further delineate the components of American ginseng that suppress colitis and prevent colon cancer. Among five different fractions of American ginseng (butanol, hexane, ethylacetate, dichloromethane, and water), a hexane fraction has particularly potent antioxidant and proapoptotic properties. The effects of this fraction were shown in a mouse macrophage cell line (ANA-1 cells), in a human lymphoblastoid cell line (TK6), and in an ex vivo model (CD4(+)/CD25(-) primary effector T cells). A key in vivo finding was that compared with the whole American ginseng extract, the hexane fraction of American ginseng was more potent in treating colitis in a dextran sodium sulfate (DSS) mouse model, as well as suppressing azoxymethane/DSS-induced colon cancer. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) labeling of inflammatory cells within the colonic mesenteric lymph nodes was elevated in mice consuming DSS + the hexane fraction of American ginseng. Results are consistent with our in vitro data and with the hypothesis that the hexane fraction of American ginseng has anti-inflammatory properties and drives inflammatory cell apoptosis in vivo, providing a mechanism by which this fraction protects from colitis in this DSS mouse model. This study moves us closer to understanding the molecular components of American ginseng that suppress colitis and prevent colon cancer associated with colitis. PMID- 22293631 TI - A phase 2 cancer chemoprevention biomarker trial of isoflavone G-2535 (genistein) in presurgical bladder cancer patients. AB - The soy compound genistein has been observed preclinically to inhibit bladder cancer growth with one potential mechanism being the inhibition of epidermal growth factor receptor phosphorylation (p-EGFR). A phase 2 randomized, placebo controlled trial investigated whether daily, oral genistein (300 or 600 mg/d as the purified soy extract G-2535) for 14 to 21 days before surgery alters molecular pathways in bladder epithelial tissue in 59 subjects diagnosed with urothelial bladder cancer (median age, 71 years). G-2535 treatment was well tolerated; observed toxicities were primarily mild to moderate gastrointestinal or metabolic and usually not attributed to study drug. Genistein was detected in plasma and urine of subjects receiving G-2535 at concentrations greater than placebo subjects' but were not dose-dependent. Reduction in bladder cancer tissue p-EGFR staining between the placebo arm and the combined genistein arms was significant at the protocol-specified significance level of 0.10 (P = 0.07). This difference was most prominent when comparing the 300-mg group with placebo (P = 0.015), but there was no significant reduction in p-EGFR staining between the 600 mg group and placebo. No difference in normal bladder epithelium p-EGFR staining was observed between treatment groups. No significant differences in tumor tissue staining between treatment groups were observed for COX-2, Ki-67, activated caspase-3, Akt, p-Akt, mitogen-activated protein kinase (MAPK), or p-MAPK. No significant differences in urinary survivin or BLCA-4 levels between treatment groups were observed. Genistein displayed a possible bimodal effect (more effective at the lower dose) on bladder cancer tissue EGFR phosphorylation that should be evaluated further, possibly in combination with other agents. PMID- 22293633 TI - Transitions that impact neonates and their families. PMID- 22293634 TI - Supporting transitions in clinical practice development. PMID- 22293635 TI - Strategies to support the transition to home. PMID- 22293636 TI - Nurse staffing legislation: an overview. PMID- 22293637 TI - Pharmacokinetic changes in the pregnant woman. PMID- 22293638 TI - Oxytocin administration: the transition to a safer model of care. AB - The use of oxytocin, a high-alert medication, has increased dramatically in recent years as induction rates have risen. Methods for administration of oxytocin and subsequent outcomes have long been a source of debate. Furthermore, one of the leading causes of obstetrical liability claims involves the administration of oxytocin leading to tachysystole. This article describes how a collaborative of Perinatal Clinical Nurse Specialists and Obstetric Nurse Educators for a 9-hospital healthcare system throughout Colorado undertook a system-wide process-improvement project to increase safety for pregnant women receiving oxytocin. The goal of this initiative was to decrease risk exposure by successfully implementing a standardized evidence-based protocol and processes across the healthcare system. There has been implementation of standardized oxytocin mixtures, low-dose administration guidelines, and safety checklists to assure fetal and maternal well-being before initiation of oxytocin and increases in oxytocin dosages. The associated outcomes after this initiative have been shorter lengths of labor, decreased incidence of tachysystole, and decreased incidence of primary cesarean birth. PMID- 22293639 TI - Oxytocin administration: the transition to a safer model of care. PMID- 22293640 TI - Relationship-based nursing practice: transitioning to a new care delivery model in maternity units. AB - In a fast-paced, high-volume maternity unit, the goal for nursing care delivery is to provide care that is perceived by patients as personal and caring, is rewarding to nurses, and is in an environment of maximum patient safety. A care delivery model is the organizing structure that can facilitate this goal. Relationship-Based Nursing Practice is a care delivery model designed to transition nursing care from task-focused to relationship-based. A shared vision of the registered nurse as a professional member of the healthcare team, working in an optimally safe and family-centered care environment, inspired the model design. Three relationships-the nurse with the patient, the nurse with colleagues, and the nurse with self-provided the foundation for the creation of guiding principles. Guiding principles were operationalized to support 1 or more of the 3 relationships, contribute to improved patient safety, and actualize the role of the professional registered nurse, in daily patient care. Outcomes include improvement in patient safety, increased patient satisfaction, and perception of improved teamwork among nurses. The process for sustainability and ongoing evaluation of the model is discussed. PMID- 22293641 TI - The Baby-Friendly journey in a US public hospital. AB - In May of 2007, San Francisco General Hospital & Trauma Center became the first Baby-Friendly certified hospital in San Francisco. This quality improvement program began in 1999 and took 8 years to complete. Challenges to completing this goal included a population that has myriad social issues including non-English speaking clients, drug abuse, poverty, and homelessness. Further complications included a constantly changing group of perinatal healthcare providers with little-to-no breast-feeding knowledge, hospital practices that did not support rooming-in and skin-to-skin contact, and lack of overall patient breast-feeding education. This article describes the process of implementing The Baby-Friendly Hospital Initiative quality improvement program, achieving certification and subsequent increase in breast-feeding rates. Breast-feeding initiation rates went from 81% in 2002 to 98% in 2010. Exclusivity rates did not change. PMID- 22293642 TI - Preventing infant abductions: an infant security program transitioned into an interdisciplinary model. AB - Ensuring the safety of infants born in a hospital is a top priority and, therefore, requires a solid infant security plan. Using an interdisciplinary approach and a systematic change process, nursing leadership in collaboration with clinical nurses and security personnel analyzed the infant security program at this community hospital to identify vulnerabilities. By establishing an interdisciplinary approach to infant security, participants were able to unravel a complicated concept, systematically analyze the gaps, and agree to a plan of action. This resulted in improved communication and clarification of roles between the nursing and security divisions. Supply costs decreased by 17.4% after the first year of implementation. Most importantly, this project enhanced and strengthened the existing infant abduction prevention measures, hard wired the importance of infant security, and minimized vulnerabilities. PMID- 22293643 TI - Transitions in the early-life of late preterm infants: vulnerabilities and implications for postpartum care. AB - The focus of this article is on the transition of late preterm infants from hospital to home. The current state of literature related to mortality, morbidities, emergency department visits, and rehospitalization underscores the vulnerability of late preterm infants following discharge from hospital. Universal provision of postpartum care to late preterm infants is viewed as an environmental support intended to facilitate transition of these vulnerable infants from hospital to home. Gaps in provision of postpartum care of late preterm infants are situated within the discussion of guidelines and models of postpartum care (home vs clinic) of late preterm infants. PMID- 22293644 TI - Support intervention needs and preferences of fathers affected by postpartum depression. AB - The effect of postpartum depression (PPD) on mothers has been extensively studied. But even though up to 50% of men whose partners suffer from PPD also have depressive symptoms, little is known about the impact of maternal PPD on fathers. Depressive symptoms are likely to decrease fathers' ability to provide maternal support. Children with 2 depressed parents are at significantly greater risk for poor developmental outcomes than those with 1 affected parent. The objective of this Canada-wide exploratory/descriptive study was to describe the support needs and preferences for support of fathers whose partners have had PPD. Qualitative methods and community-based research approaches were used, and one-to one telephone interviews were conducted between 2009 and 2011 with a total of 40 fathers. Fathers desired support from both formal (professional) and informal (friends and family) sources and noted that ideal support interventions should cover a number of key topics including information on PPD and practical tips on how to cope with their partner's PPD. Fathers reported that the ideal PPD intervention program does not favor any one setup and, to reach the full spectrum of parents, the program must be multitiered, accessible, and as flexible as funding allows. PMID- 22293645 TI - Transition from hospital to home for parents of preterm infants. AB - Research on the phenomenon of transition spans several decades. This article discusses the transition from hospital to home and the challenges parents of preterm infants experience during a neonatal intensive care unit stay and after discharge. The article explores the link between parental problems and rehospitalizations and the need for accurate measures of transitional concerns. An example of a theoretical model and instrument is described. PMID- 22293647 TI - Transition to neonatal follow-up programs: is attendance a problem? AB - Neonatal follow-up (NFU) programs provide health services for infants at high risk for developmental problems after they transition home from the neonatal intensive care unit (NICU). The purpose of the study was to assess current patterns of NFU attendance and explore time points when mothers and infants withdrew from NFU programs during the infant's first year of life. The study was conducted in 3 Canadian tertiary-level NICUs that referred to 2 affiliated, regional NFU programs. A total of 357 mothers and 400 infants were consecutively recruited during NICU hospitalization. Attendance at NFU programs was tracked at each of the 3 scheduled appointments from existing NFU databases. Attendance at NFU decreased over time from 84% at the first appointment to 74% by 12 months, with the highest withdrawal from NFU after NICU discharge, followed by withdrawal after the first NFU appointment. Nonattendance at NFU results in less access to required services and underreporting of the developmental outcomes of these infants. Given these findings, mothers should be screened earlier in the NICU to identify those at greatest risk of not attending NFU. Strategies should be implemented to address potential barriers and provide effective transition and access to the NFU program. PMID- 22293648 TI - A new year's resolution. PMID- 22293649 TI - Molecular beam epitaxial growth and characterization of catalyst-free InN/InxGa1 xN core/shell nanowire heterostructures on Si(111) substrates. AB - We report on the achievement of, for the first time, InN/InGaN core/shell nanowire heterostructures, which are grown directly on Si(111) substrates by plasma-assisted molecular beam epitaxy. The crystalline quality of the heterostructures is confirmed by transmission electron microscopy, and the elemental mapping through energy dispersive x-ray spectrometry further reveals the presence of an InGaN shell covering the sidewall and top regions of the InN core. The optical characterizations reveal two emission peaks centered at ~1685 nm and 1845 nm at 5 K, which are related to the emission from the InGaN shell and InN core, respectively. The InN/InGaN core/shell nanoscale heterostructures exhibit a very high internal quantum efficiency of ~62% at room temperature, which is attributed to the strong carrier confinement provided by the InGaN shell as well as the nearly intrinsic InN core. PMID- 22293651 TI - Risk factors associated with coronary artery calcification should be examined before kidney transplantation. AB - The best treatment for end stage renal disease (ESRD) patients is kidney transplantation, but the renal transplant recipients still have a higher incidence of cardiovascular events compared with general population. Cardiovascular risk factors were imposed long before ESRD, as the majority of patients starting dialysis or kidney transplantation already have signs of advanced atherosclerosis. Artery calcification is an organized, regulated process similar to bone formation. Coronary artery calcification (CAC) is found frequently in advanced atherosclerotic lesions and could be a useful marker of them. We evaluated the prevalence of CAC in 49 stable renal transplant recipients and in 48 age- and gender-matched patients with chronic kidney disease (CKD) in stages 2-5 not requiring dialysis to assess risk factors associated with CAC. Computed tomography was used for CAC detection and quantification (CAC score). The prevalence of CAC was 43.8% in transplant recipients and 16.7% in CKD patients (p < 0.001). Transplant recipients with CAC were significantly older and had longer duration of CKD and/or dialysis than recipients without CAC. In contrast, the serum levels of fetuin A (an inhibitor of vascular calcification) and albumin were significantly lower in CKD patients with CAC than those without CAC. During the observation period (30 months), 30 patients, including 23 CKD patients, began dialysis, and 4 transplant recipients and 2 CKD patients died. Independent predictors of mortality were age, serum amyloid A and the CAC score. In conclusion, the examination and prevention of risk factors associated with atherosclerosis should be started at the beginning of renal failure. PMID- 22293652 TI - Benefits from apical chest tube drainage in pneumothorax. AB - Pneumothorax is the accumulation of air in the pleural space. Pneumothorax may occur spontaneously (primary spontaneous pneumothorax, PSP). Chest tube drainage (CTD) is the most common choice for treatment of PSP. This study aimed to evaluate patients treated with CTD, regarding demographic and diagnostic characteristics, and to compare the effectiveness of apical and axillary approaches. We retrospectively analyzed a total of 217 patients with PSP regarding symptoms, duration of complaints, and treatment procedures. There were 196 (90.3%) male patients and mean age was 25.22 +/- 5.37 years. The approach of CTD was determined randomly; being performed with the apical approach on 93 (42.9%) and axillary on 124 patients (57.1%). There were no statistically significant differences between the two groups in terms of age, sex, BMI, collapse size, and complaint duration. However, a statistically significant relationship was determined between collapse size and leading symptoms where the significance was related to dyspnea (p < 0.001). This led to the thought that dyspnea increases with the increase of collapse size. The patients who were admitted to hospital in the later term when compared with others, had a larger collapse size (p < 0.001). This also led to the thought that collapse increases in relation to time due to late admission of patients. Hospitalization time was significantly shorter in patients who had apical CTD (p < 0.001). In conclusion, inserting the tube from the apex could shorten the treatment period. PMID- 22293653 TI - Lipothiophosphoramidates for gene delivery: critical role of the cationic polar headgroup. AB - When considering a family of cationic lipids designed for gene delivery, the nature of the cationic polar head probably has a great influence on both the transfection efficacy and toxicity. Starting from a cationic lipothiophosphoramidate bearing a trimethylammonium headgroup, we report herein the impact on gene transfection activity of the replacement of the trimethylammonium moiety by a trimethylphosphonium or a trimethylarsonium group. A series of three different human epithelial cell lines were used for the experimental transfection studies (HeLa, A549 and 16HBE14o(-)). The results basically showed that such structural modifications of the cationic headgroup can lead to a high transfection efficacy at low lipid/DNA charge ratios together with a low cytotoxicity. It thus appears that the use of a trimethylarsonium cationic headgroup for the design of efficient gene carriers, which was initially proposed in the lipophosphoramidate series, can be extended to other series of cationic lipids and might therefore have great potential for the development of novel non viral vectors in general. PMID- 22293654 TI - Breast cancer biomarkers predict weight loss after gastric bypass surgery. AB - BACKGROUND: Obesity has long been associated with postmenopausal breast cancer risk and more recently with premenopausal breast cancer risk. We previously observed that nipple aspirate fluid (n) levels of prostate specific antigen (PSA) were associated with obesity. Serum (s) levels of adiponectin are lower in women with higher body mass index (BMI) and with breast cancer. We conducted a prospective study of obese women who underwent gastric bypass surgery to determine: 1) change in n- and s-adiponectin and nPSA after surgery and 2) if biomarker change is related to change in BMI. Samples (30-s, 28-n) and BMI were obtained from women 0, 3, 6 and 12 months after surgery. FINDINGS: There was a significant increase after surgery in pre- but not postmenopausal women at all time points in s-adiponectin and at 3 and 6 months in n-adiponectin. Low n-PSA and high s-adiponectin values were highly correlated with decrease in BMI from baseline. CONCLUSIONS: Adiponectin increases locally in the breast and systemically in premenopausal women after gastric bypass. s-adiponectin in pre- and nPSA in postmenopausal women correlated with greater weight loss. This study provides preliminary evidence for biologic markers to predict weight loss after gastric bypass surgery. PMID- 22293655 TI - Cytoplasmic rods and rings autoantibodies developed during pegylated interferon and ribavirin therapy in patients with chronic hepatitis C. AB - BACKGROUND: Serum autoantibodies are frequently detected in patients with chronic HCV infection, reflecting the wide spectrum of immune reactions related to this virus. In the present study, a novel autoantibody to cytoplasmic rods and rings (RR) in chronic HCV patients was characterized. METHODS: Sera from 75 previously untreated HCV patients were investigated by indirect immunofluorescence using HEp 2 cell substrate before and during pegylated interferon (PEG-IFN)/ribavirin (RBV) therapy. HEp-2 cells were cultured and fixed either following standard protocols or with the addition of RBV in culture medium. RESULTS: In 15 out of 75 (20%) patients, analysis revealed the presence of antibodies to rod-like cytoplasmic structures ranging approximately 3-10 MUm in length and rings approximately 2-5 MUm in diameter. These RR structures became detectable in >95% of cells after addition of RBV in culture medium, whereas they were absent in untreated cells. Anti-RR antibodies were found in sera collected during PEG-IFN/RBV treatment only, but never detected before antiviral therapy nor in control groups. More importantly, these anti-RR antibodies were more often detected in non responder/relapsers than in responder patients (33% versus 11%; P-value =0.037). CONCLUSIONS: An RBV-induced autoantibody was identified to a new cytoplasmic autoantigenic structure developed in HCV patients after PEG-IFN/RBV and this same structure can be induced by RBV in in vitro culture. Owing to the onset of anti RR antibodies in PEG-IFN/RBV-treated patients and their association with a treatment failure, studies are deemed necessary to clarify whether anti-RR plays a role in the response to PEG-IFN/RBV therapy. PMID- 22293656 TI - Biological-like vesicular structures self-assembled from DNA-block copolymers. AB - The polymer modification of short nucleotide sequences has been achieved for future use as self-assembled biologically active structures with sizes in the nanometre range. Co-assembly of the resulting DNA-based amphiphilic block copolymers with native proteins demonstrates the self-assembly of biological-like vesicular structures. PMID- 22293657 TI - First reported case of the Swedish new variant of Chlamydia trachomatis (nvCT) in Eastern Europe (Russia), and evaluation of Russian nucleic acid amplification tests regarding their ability to detect nvCT. PMID- 22293658 TI - Autophagy-regulating small molecules and their therapeutic applications. AB - Autophagy or self-eating is a complicated cellular process that is involved in protein and organelle digestion occurring via a lysosome-dependent pathway. This process is of great importance in maintaining normal cellular homeostasis. However, disruption of autophagy is closely associated with various human diseases such as cancer, neurodegenerative disorders, heart disease and pathogen infection. Therefore, small molecules that modulate autophagy can be employed to dissect this complex process and ultimately could have high potential for the treatment of a variety of diseases. This critical review discusses general aspects of autophagy, autophagy-associated diseases and autophagy regulators for biological research and therapeutic applications (207 references). PMID- 22293659 TI - Treatment with the PARP-inhibitor PJ34 causes enhanced doxorubicin-mediated cell death in HeLa cells. AB - Adjuvant therapies can incorporate a number of different drugs to minimize the cardiotoxicity of cancer chemotherapy, decrease the development of drug resistance and increase the overall efficacy of the treatment regime. Topoisomerase IIalpha is a major target of many commonly used anticancer drugs, where cell death is brought about by an accumulation of double-strand DNA breaks. Poly (ADP-ribose) polymerase (PARP)-1 has been extensively studied for its role in the repair of double-strand DNA breaks, but its ability to add highly negative biopolymers (ribosylation) to target proteins provides a vast number of pathways where it can also be important in mediating cell death. In this study, we combine the classical topoisomerase IIalpha poison doxorubicin with the PARP inhibitor PJ34 to investigate the potentiation of chemotherapeutic efficiency in HeLa cells. We demonstrate that PJ34 treatment has the capacity to increase endogenous topoisomerase IIalpha protein by about 20%, and by combining doxorubicin treatment with PJ34, we observed a 50% improvement in doxorubicin-mediated cell death in HeLa cells. These results were correlated with the ribosylation of transcription factor specificity factor 1 after doxorubicin treatment, thereby altering its affinity for binding to known regulatory elements within the human topoisomerase IIalpha promoter. Taken together, these results highlight the synergistic potential of combining PARP inhibitors with classical topoisomerase IIalpha-targeting drugs. PMID- 22293660 TI - A prolonged complete response in a patient with BRAF-mutated melanoma stage IV treated with the MEK1/2 inhibitor selumetinib (AZD6244). AB - In melanoma, the RAS/RAF/MEK/ERK pathway is frequently activated by mutations in BRAF and NRAS. Selumetinib (AZD6244) is an oral, selective, non-ATP-competitive inhibitor of MEK1/2. Here, we describe a patient with metastatic melanoma (T1N2cM1a) with a BRAF V600E mutation. She is currently being treated with selumetinib 75 mg twice daily in a phase I trial and has shown complete response for the past 4 years. This case report raises questions regarding treatment schedule, treatment duration and management of adverse events. PMID- 22293661 TI - Henoch-Schonlein purpura associated with solid-organ malignancies: three case reports and a literature review. AB - Adult Henoch-Schonlein purpura (HSP) is rarely associated with solid-organ malignancies. We describe here three adult patients with HSP diagnosed within 3 months of the diagnosis of associated solid-organ malignancies, including pulmonary, prostate, and renal carcinomas. Two patients had complete remission with a combination of immunosuppressive therapies and treatment of the associated malignancy. The third patient had partial remission with immunosuppressive therapies, but never received treatment for the associated malignancy and did not achieve complete remission before his death 10 months after diagnosis of HSP. These cases suggest that HSP associated with solid-organ malignancies may be resistant to immunosuppressive therapies without treatment of the associated malignancy. Therefore, evaluation for solid-organ malignancies should be considered in adult patients without an identifiable cause of HSP, especially if the disease is not self-limited or does not respond appropriately to treatment. PMID- 22293662 TI - Dendrites: Ensuring appropriate coverage. PMID- 22293663 TI - Pain: A new trick for opioids? PMID- 22293664 TI - Comparing effectiveness of 3 learning strategies: simulation-based learning, problem-based learning, and standardized patients. AB - INTRODUCTION: Curricula must not only provide students with knowledge but also foster the development of critical thinking and reasoning skills. Several learning strategies, including problem-based learning (PBL), standardized patients, and high-fidelity human simulation, have been incorporated into courses; however, it is currently unknown which technique is the most effective. METHODS: This is a prospective, randomized, crossover study that was conducted during two 90-minute seizure disorder laboratory sessions for PharmD students in their third professional year. Students rotated between 3 different seizure disorder cases (A, B, and C), with each student experiencing 3 learning strategies including PBL, standardized patients, and high-fidelity human simulation. Evaluation of knowledge consisted of quizzes at the end of each case, and student perception and satisfaction were evaluated by an anonymous survey at the conclusion of the laboratory sessions. RESULTS: Student quiz scores from the simulation learning strategy were statistically better than those from the standardized interview and modified PBL (mPBL) strategies in cases A and B (P < 0.001). The student quiz scores for the standardized interview were also statistically better than the mPBL scores in case C (P = 0.001). When surveyed, 91% of students agreed or strongly agreed that simulation improved their knowledge, whereas only 69% and 67% of students agreed or strongly agreed that mPBL or standardized patients, respectively, improved their knowledge (P < 0.001). CONCLUSIONS: High-fidelity simulation is an effective learning strategy. When it is compared with standardized patients and mPBL strategies, students performed better on knowledge-based quizzes and had higher levels of satisfaction. PMID- 22293665 TI - Simulation-based training of extracorporeal membrane oxygenation during H1N1 influenza pandemic: the Italian experience. AB - On November 2009, the Italian health authorities set up a network of selected intensive care unit (ICU) centers (ECMOnet) to prepare for the treatment of the sickest patients of influenza A (H1N1) by means of extracorporeal membrane oxygenation (ECMO).To quickly and efficaciously train all the physicians working in the ICUs of the ECMOnet on ECMO use, we decided to take advantages of the opportunity provided by simulation technology.Simulation proved efficacious in providing adequate training and education to participants as confirmed by the survival results obtained by the group of ICUs of the ECMOnet.Our experience supports the use of simulation as a valuable alternative to animal laboratory sessions proposed by traditional ECMO training programs providing participants with cognitive, technical, and behavioral skills and allowing a proficient transfer of those skills to the real medical domain. PMID- 22293666 TI - Production of large-scale, freestanding vanadium pentoxide nanobelt porous structures. AB - Large-scale, freestanding, porous structures of vanadium pentoxide nanobelts (VPNs) were successfully prepared using the template-free freeze-drying method. The porous and multi-layered VPN macrostructures are composed of randomly oriented long nanobelts (over 100 MUm) and their side length can be controlled up to a few tens of centimetres. Also, the bulk density and surface area of these macrostructures are 3-5 mg cm(-3) and 40-80 m(2) g(-1), respectively, which are similar to those of the excellent adsorbents. In addition, the removal efficiency measurements of ammonia molecules revealed that the VPN porous structures can adsorb the ammonia molecules with the combinations of van der Waals forces and strong chemical bonding by functional groups on the VPN surface. PMID- 22293667 TI - Crisis management and recovery from the damage to the laboratory animal production facility due to the Great East Japan Earthquake. AB - Charles River Laboratories Japan produces laboratory animals, mainly mice and rats. In its history, we have experienced many crises such as mass food poisoning of staff and contamination of animals. However, we overcame these crises, accomplishing our corporate missions to secure steady supply of healthy animals. Under such circumstances, in 2008, we faced an unprecedented crisis involving a novel influenza possibly becoming pandemic. Therefore, we prepared a Crisis Management Plan (CMP) and Business Continuity Plan (BCP) to avoid the worst case scenario. Fortunately, the novel influenza did not develop into a pandemic and no major problems occurred in production of our laboratory animals. In March 2011, our Tsukuba Breeding Center was struck by the Great East Japan Earthquake. Many cages fell from racks, and consequently, 14,000 mice and rats were euthanized. Moreover, this animal production facility experienced not only blackouts and water outage but also various maintenance problems. After triage of the animals, almost half of the animals kept were eventually lost. However, we recovered and resumed shipment of animals two weeks after the disaster by utilizing the CMP and BCP we initially created as a countermeasure against novel influenza. After two months, our production volume returned to normal except for two strains. I sincerely hope this review, which highlights our experience and related issues, will be a useful resource in regard to crisis management for people who are engaged in laboratory animal care and use. PMID- 22293668 TI - Histological properties of the glomerular layer in the mouse accessory olfactory bulb. AB - In mammals, the vomeronasal system (VS) originating from the vomeronasal organ (VNO; also called "Jacobson's organ") is considered to be a chemosensory system that recognizes "pheromone" signals. In the accessory olfactory bulb (AOB), the primary center of the VS, the glomerular cell layer (GL) of the AOB is regarded as an important functional area in the transmission of pheromone signals from vomeronasal sensory neurons (VSNs) of the VNO. In mice, the most frequently used animal model for the study of the VS, the GL of the AOB has several unique histological properties when compared with the main olfactory bulb (MOB): (i) each glomerular size is far smaller than in the MOB; (ii) many juxtaglomerular cells (JGCs) are GABA immunopositive, but subpopulations of cells distributed in the AOB are tyrosine hydroxylase- or calcium-binding protein immunopositive; and (iii) the dendritic branching pattern of the JGC in the AOB is heteromeric. The biological significance of the mammalian VS is still debated. The unique histological properties of the mouse AOB summerized in the present review may give some useful information that may help in understanding the function of the mammalian VS. PMID- 22293669 TI - Japanese wild mice: a rich resource for new disease models. AB - Breeding of fancy mice has been a tradition in Japan. Recent progress in animal science has shed a new light on Japanese wild-derived mice as tools for discovery of new disease models because these mice, Mus musculus molossinus, are genetically far remote from the majority of available laboratory mice. After decades of effort, five inbred strains of mice have been established from pairs of wild mice trapped in Tohoku, northeastern Japan, namely KOR1/Stm, KOR5/Stm, KOR7/Stm, AIZ/Stm, and MAE/Stm. They carried numerous mutations, leading to a variety of diseases. During the inbreeding of KOR1, the first spontaneous mutation was found in the Apoe (apolipoprotein E) gene, and the mutant was later designated as spontaneous hyperlipidemic (SHL). Thereafter, a number of other mutations were discovered among wild-derived inbred strains, including atopic dermatitis, microphthalmia, dominant white spots, sebaceous gland abnormalities, and audible song-like vocalization. Furthermore, to examine the possible effects of the genetic background for these mutant genes, sets of congenic strains were generated, in which the mutant gene was introduced into at least 3 different strains of laboratory mice, including BALB/c and C57BL/6. These congenic strains have now been established as novel disease models. These wild-derived inbred strains serve as a treasure trove for novel disease models. Most of them have been deposited in the Riken BioResource Center (BRC), and some are also available from commercial breeders. PMID- 22293670 TI - Evaluation of four antiseptics using a novel murine norovirus. AB - We isolated a novel murine norovirus (MNV), MT30-2 strain, from feces of conventional mice in Japan to evaluate the virucidal activity of four antiseptics. The MNV MT30-2 strain was inactivated by as little as 0.2% (w/v) povidone-iodine (PVP-I) and 0.1% (w/v) sodium hypochlorite (NaOCl) treatment as determined by a novel plaque assay. Importantly, PVP-I reduced the MNV titer by 4 log(10) within 15 s of exposure. The other two antiseptics, benzethonium chloride (BEC) and chlorhexidine gluconate (CHG), did not reduce the MNV titer even when treatment lasted for 60 s. When the virus titer was reduced by PVP-I or NaOCl treatment, the amount of MNV RNA was not reduced, indicating that the presence of viral RNA was not related to the virucidal activity of the antiseptics. PVP-I and NaOCl will be useful in controlling the spread of MNV, which is a common problem in mice colonies. In this study, we isolated a novel MNV and newly revealed that two antiseptics (PVP-I and NaOCl) were able to inactivate MNV at low concentrations and in a short contact time. PMID- 22293671 TI - Establishment of a lens epithelial cell line from a canine mature cataract. AB - The aim of this study was to establish a lens epithelial cell (LEC) line originated from a cataract of a dog. An anterior capsulorhexis specimen from a dog naturally developing mature cataracts was obtained prior to routine phacoemulsification cataract extraction. The primary lens epithelial cells were transfected with expression plasmid DNA encoding the large T antigen of replication origin-defective simian virus 40 (SV40), and then a colony was cloned using a glass cylinder. The primary cells stopped proliferation in three passages, while the transfected cells remained proliferative. Functional analysis of Na-dependent vitamin C transporter (SVCT) indicated that the Km value toward ascorbic acid (vitamin C) was 19.9 +/- 2.8 uM, and RT-PCR analysis showed that SVCT2 was observed in this cell line while SVCT1 was not, which is one of the characteristics of LECs. Western blot analysis and cytoimmunochemistry indicated immortalized cells produced a protein with a molecular mass of 25 kDa, which reacted with an antibody to alphaB-crystallin within the whole cytosol. The cloned cell line, termed cdLEC, grew well and could be propagated over 250 times by basically splitting at 1:20. These results indicate that cdLEC may also provide a useful in vitro system for the study of the pathophysiology of cataract. PMID- 22293672 TI - A novel diabetes mellitus mouse model, MAFA-deficient and beta cell-specific MAFK overexpressing hybrid transgenic mice, developed severe diabetic nephropathy and improved with TCV-116 (candesartan cilexetil) treatment. AB - Many models of diabetic nephropathy have been reported. However, it is rare that the characteristic findings of severe human diabetic nephropathy, such as diffuse, nodular, and exudative lesions, are all detected in one model mouse. Previously, we reported that MAFA-deficient and beta cell-specific MAFK overexpressing hybrid transgenic (Mafa(-/-)Mafk (+)) mice develop diabetes mellitus and, after uninephrectomy, demonstrate these characteristic lesions. In this study, we administered TCV-116 (candesartan cilexetil) to Mafa(-/-)Mafk (+) mice after uninephrectomy and examined whether TCV-116 ameliorated the diabetic nephropathy. We also evaluated the utility of these mice as a model for developing treatments for diabetic nephropathy. We performed uninephrectomy of the Mafa(-/-)Mafk (+) mice at 8 weeks old. We then divided these mice into two groups as follows: 1) an untreated group and 2) a group treated with TCV-116 at 5 ug/g/day from 10 to 20 weeks. TCV-116 treatment did not affect serum glucose levels. However, in the treated group, urinary protein excretion, mesangial matrix expansion, enlargement of the kidney, and glomerular surface area were all improved relative to untreated mice. Oxidative stress is known to be increased in diabetic nephropathy and to be suppressed by TCV-116. The urinary level of 8 OHdG, an oxidative stress marker, at 20 weeks was lower in the TCV-116-treated group than in the untreated group. From these results, we concluded that the Mafa(-/-)Mafk (+) mouse is a useful model to analyze diabetic nephropathy and a useful tool for the development of new drugs to treat diabetic nephropathy. PMID- 22293673 TI - Differential age-related bone architecture changes between female and male STR/Ort mice. AB - The incidence of spontaneous osteoarthritis (OA) in female STR/Ort mice is much lower than that observed in male STR/Ort mice; however, the reason for the differential incidence of OA between sexes has not been elucidated. Here, we investigated and compared age- and sex-related bone mineral density and architectural changes in male and female STR/Ort mice. Bone architecture and bone mineral density (BMD) of femurs were examined in 5-, 10-, 15-, 20-, and 35-week old male and female STR/Ort mice by microscopic computed tomography (uCT). Angular degrees of internal tibial torsion (ADITT) were also measured in mice at 5, 15, and 35 weeks of age. Earlier decreases of cancellous volume and BMD were found in male STR/Ort mice. Using uCT, an age-related decline of bone marrow space in femoral diaphysis was observed in both males and females but was more dramatic in females. In addition, an earlier increase of ADITT was observed in male STR/Ort mice, suggesting that internal rotation of the tibia may contribute to OA. Age- and sex-related bone architectural changes clearly differ between male and female STR/Ort mice. These differences in bone structure, particularly ADITT, may explain the differential incidence of OA in STR/Ort mice. PMID- 22293674 TI - Identification of whey acidic protein (WAP) in dog milk. AB - Whey acidic protein (WAP) has been identified as a major whey protein in milk of a wide range of species and reportedly plays important roles in regulating the proliferation of mammary epithelial cells. However, in some species including humans, WAP is not synthesized in the mammary gland. The presence of WAP in carnivore species has not been reported. We searched the National Center for Biotechnology Information (NCBI) database for the dog WAP gene and tried biochemically to identify WAP in dog milk. The nucleotide sequence of the examined dog genomic DNA was completely identical to that in the NCBI database and showed that the dog WAP gene, like other known functional WAP genes, has four exons. Biochemical analysis of milk protein by reverse-phase HPLC and Western blotting demonstrated the presence of WAP in dog milk. PMID- 22293675 TI - Effect of orange oil on the oral absorption of enrofloxacin in rats. AB - This study was conducted to evaluate the oral absorption of enrofloxacin (ENFX) in rats when administered with orange oil or its main component, limonene. Compared with the group administered ENFX alone, the ENFX + limonene group did not show any significant difference in the absorption of ENFX, whereas the extent and rate of absorption of ENFX were significantly decreased in the ENFX + orange oil group (C(max), -43%; T(max), 129%). In addition, t(1/2lambdaz) and MRT of ENFX were prolonged by the concomitant administration of orange oil. The AUCs of ENFX were not affected in the ENFX + orange oil group. These results suggest that decreased oral absorption could reduce the efficacy of ENFX therapy in animals. PMID- 22293676 TI - Effect of carbon source and COD/NO3--N ratio on anaerobic simultaneous denitrification and methanogenesis for high-strength wastewater treatment. AB - The effect of carbon source and COD/NO(3)(-)-N ratio on denitrification and methanogenesis in mixed methanogenic matrix was investigated in this study. Industrial wastewater, anaerobic treated cassava stillage (CS) and glucose synthetic wastewater were used as carbon sources respectively for comparison. Experimental results showed that denitrification was the main nitrate reduction pathway for all COD/NO(3)(-)-N ratios tested in two substrates. Simultaneous denitrification and methanogenesis occurred at COD/NO(3)(-)-N higher than 7 regardless of carbon sources. Incomplete denitrification was observed at COD/NO(3)(-)-N ratio below 7 in both the anaerobic effluent of CS and glucose-fed cultures due to the insufficient available organic carbon. The nature of carbon sources was observed to play a key role in the nitrate and organic carbon utilization rates. COD/NO(3)(-)-N ratio had a strong effect on the organic matter utilization pathways. Methanization consumed more organic matter than denitrification with further increase of COD/NO(3)(-)-N ratio above 7 in two substrates. Results of VFA variation suggested that propionate and butyrate were preferably utilized by the denitrifiers than acetate. PMID- 22293677 TI - Tooth loss and edentulism in the Turkish elderly. AB - The aim of this study was to evaluate partial and complete tooth loss and some related demographic factors, and oral health behaviors among Turkish elderly. According to recent censuses, elderly population of Turkey is rapidly growing. There is no nationwide information related to edentulism and natural teeth retention among 65-74 year-old people in Turkey. In this nationwide representative cross-sectional study, 1545 subjects aged 65-74 years were evaluated using the proportional stratified cluster sampling method. The data were collected via a structured, pre-tested face to face administered questionnaire and an oral examination. Chi-square test and binary logistic regression analyses were used to determine the significance of explanatory variables. 48.0% of elderly were edentate. The mean DMF-T was 25.8+/-8.5. These values were higher in women (p=0.016), older age (p<0.001) and rural individuals (p<0.001). Only 12.4% of the subjects had functional dentition. Age, visiting dentist, and health security were associated with edentulism. Female sex (OR=1.37), 70-74 age group (OR=2.08) and illiteracy (OR=3.25) were the independent factors of not having functional dentition. A reduction in edentulism in elderly may be achieved by the implementation of community programs promoting oral health for the prevention and treatment. PMID- 22293678 TI - The effects of passive warm-up vs. whole-body vibration on high-intensity performance during sprint cycle exercise. AB - The purpose of this study was to compare the effects of passive warm-up (PW), whole-body vibration (WBV), and control (C) on high-intensity performance during sprint cycle exercise. Six recreationally trained men performed a 30-second sprint cycle test after the 3 aforementioned conditions; each test was carried out on a different day after balanced-order experimental tests. The WBV consisted of 5 minutes of squats associated with WBV (45 Hz, 2 mm). The PW consisted of 30 minutes of PW using a thermal blanket on the thighs and legs (35 W). The C consisted of 30 minutes of no warm-up with the subject lying down. Motor neuron excitability from the vastus lateralis muscle, evaluated by electromyography (EMG), was determined before exercise at rest and during sprint cycle exercise. Blood lactate levels (BLs), evaluated by spectroscopy, and muscle temperature (MT) of the thigh, estimated indirectly by measuring skin temperature, were determined at following time points: before exercise at rest (before and after experimental conditions), immediately, and 3 minutes after the 30-second sprint cycle test. Peak power, relative power, relative work, time of peak power, and pedaling cadence were significantly higher in the WBV compared with that for C (p < 0.05). Although MT was significantly greater in PW compared with that in WBV and C before exercise (p < 0.01), no significant differences were observed between the experimental conditions for BL immediately after sprint cycle exercise (p = 0.35) and in EMG during sprint cycle exercise (p = 0.16). Thus, it is plausible to suggest WBV as a method for an acute increase in high-intensity performance during sprint cycle exercise for athletes immediately before competition or training. PMID- 22293679 TI - Intensity control in swim training by means of the individual anaerobic threshold. AB - This study aimed at evaluating the homogeneity of physiological responses during swim training bouts with intensities prescribed by reference to the individual anaerobic threshold (IAT). Eighteen competitive front crawl swimmers (female 5, male 13, 10 long-distance, and 8 short-distance swimmers [LDSs, SDSs], age: 17 +/ 1.7 years, training history: 7.0 +/- 2.8 years, training volume per week: 35 +/- 5.7 km) performed an incremental swimming test to determine the IAT. Within a maximum of 3 weeks, 4 training programs were conducted: 20 * 100-m low-intensity endurance training (EN(low), 97% IAT), 5 * 400-m high-intensity endurance training (EN(high), 101% IAT), 5 * 200 m (IT1, 105% IAT), and 10 * 100 m (IT2, 108% IAT) intensive interval training. Blood lactate concentrations (bLa) were determined during each training session. The results are given as median (25th and 75th percentiles). During EN(low) and EN(high), the mean bLas were 1.8 mmol.L(-1) (1.3/3.0 mmol.L(-1)) and 4.4 mmol.L(-1) (3.9/6.4 mmol.L(-1)). The bLas were higher during both IT programs: IT1, 6.3 mmol.L(-1) (5.6/7.2 mmol.L(-1)); IT2, 5.8 mmol.L(-1) (5.0/6.5 mmol.L(-1)). The bLas of most individuals were close to the median values (+/-2.4 mmol.L(-1)). However, in each of the training programs, some subjects showed bLa values that were clearly above (3-7 mmol.L(-1) higher). In particular, SDSs reached higher bLas at the same intensity compared with LDSs. It is concluded that intensity prescriptions by means of IAT seem to elicit an expected metabolic response in approximately 85% of swim training sessions. The observed average bLa is in the range of those recommended in the scientific literature. PMID- 22293680 TI - Low-dose caffeine administered in chewing gum does not enhance cycling to exhaustion. AB - Low-dose caffeine administered in chewing gum does not enhance cycling to exhaustion. The purpose of the current investigation was to examine the effect of low-dose caffeine (CAF) administered in chewing gum at 3 different time points during submaximal cycling exercise to exhaustion. Eight college-aged (26 +/- 4 years), physically active (45.5 +/- 5.7 ml.kg(-1).min(-1)) volunteers participated in 4 experimental trials. Two pieces of caffeinated chewing gum (100 mg per piece, total quantity of 200 mg) were administered in a double-blind manner at 1 of 3 time points (-35, -5, and +15 minutes) with placebo at the other 2 points and at all 3 points in the control trial. The participants cycled at 85% of maximal oxygen consumption until volitional fatigue and time to exhaustion (TTE) were recorded in minutes. Venous blood samples were obtained at -40, -10, and immediately postexercise and analyzed for serum-free fatty acid and plasma catecholamine concentrations. Oxygen consumption, respiratory exchange ratio, heart rate, glucose, lactate, ratings of perceived exertion, and perceived leg pain measures were obtained at baseline and every 10 minutes during cycling. The results showed that there were no significant differences between the trials for any of the parameters measured including TTE. These findings suggest that low dose CAF administered in chewing gum has no effect on TTE during cycling in recreational athletes and is, therefore, not recommended. PMID- 22293681 TI - Evaluation of HOXB13 as a molecular marker of recurrent prostate cancer. AB - Many patients with prostate cancer have disease recurrence following surgical removal of tumors and fail to respond to androgen ablation therapy. Despite the existence of a number of clinical/pathological factors, it is not possible to predict which patients will fall into this category. The results of our previous studies demonstrated that the HOXB13 homeodomain protein plays a key role in the development of prostate cancer and the progression of this malignancy. In addition, HOXB13 has been reported to predict estrogen-resistant breast cancer tumors. The purpose of this study was to investigate whether HOXB13 could be used as a molecular marker to predict prostate cancer recurrence. To examine the role of HOXB13 as a molecular marker with clinical/pathological data, the expression of HOXB13 was compared using immunohistochemistry in 57 organ-confined prostate cancer tumors obtained by radical prostatectomy. There was no significant correlation between the expression of HOXB13 and most clinical/pathological parameters, including tumor margin, invasion, pathological stage and risk level. The HOXB13 expression levels correlated with the Gleason score and there was a positive correlation with the pre-operative prostate specific antigen (PSA) levels. Accordingly, the tumor specimens from 4 patients who ultimately had biochemical failure (PSA >0.2 ng/ml), all showed a high expression of HOXB13, while their risk levels were either intermediate or high. This is the first study to report that HOXB13, together with other clinical/pathological factors, can be used as a molecular marker to predict the progression of prostate cancer. PMID- 22293682 TI - miR-10b promotes cell invasion through RhoC-AKT signaling pathway by targeting HOXD10 in gastric cancer. AB - MicroRNAs play critical roles in tumorigenesis as either oncogenes or tumor suppressors. As a microRNA induced by Twist, miR-10b function as a metastasis driver in different types of cancer, in which the downstream target gene HOXD10 is the main mediator. In gastric tumor species, miR-10b levels were dramatically elevated in lymphoma node metastasis-positive tumor tissues compared with lymphoma node metastasis-free tumor tissues, and were correlated to dowregulation of HOXD10 expression. In gastric cell lines with distinct degrees of differentiation, miR-10b was highly expressed in the cell line with strong metastatic ability. In MNK45 cells, inhibition of miR-10b led to abrogation of cell invasion. While in GES-1 cells, miR-10 overexpression resulted in enhancement of invasiveness through translational inhibition of HOXD10, and constitutive expression of HOXD10 reversed the effects of miR-10b on cell invasion. Furthermore, either knockdown of RhoC or inhibition of AKT activation interfered miR-10-induced invasiveness in GES-1 cells. In summary, these observations suggest that miR-10b can stimulate the upregulation of RhoC and AKT phosphorylation through targeting HOXD10, thus promoting cell invasion in gastric tumors. PMID- 22293683 TI - The simple view of reading redux: vocabulary knowledge and the independent components hypothesis. AB - This study investigated the hypothesis that the contributions of oral language comprehension (C) and word recognition (D) to reading comprehension (R) in the simple view of reading (SVR) are not independent because a component of C (vocabulary knowledge) directly contributes to the variance in D. Three analysis procedures (hierarchical regression analysis, exploratory factor analysis, and structural equation modeling) were used to analyze data obtained from a sample (N = 122) of 7-year-old students who were administered tests of vocabulary knowledge, nonword reading, word recognition (two standardized tests), and parallel forms of listening and reading comprehension. Results from the regression analysis indicated that vocabulary made a contribution to R beyond that made by word recognition and listening comprehension; results from the exploratory factor analysis showed that two factors (Decoding and Linguistic Comprehension) were extracted, with vocabulary and listening comprehension loading highly on the Linguistic Comprehension factor; and results from structural equation modeling revealed that the latent construct, C, influenced R not only directly but also indirectly through the latent construct, D. PMID- 22293684 TI - Components and context: exploring sources of reading difficulties for language minority learners and native English speakers in urban schools. AB - Drawing on the cognitive and ecological domains within the componential model of reading, this longitudinal study explores heterogeneity in the sources of reading difficulties for language minority learners and native English speakers in urban schools. Students (N = 150) were followed from first through third grade and assessed annually on standardized English language and reading measures. Structural equation modeling was used to investigate the relative contributions of code-related and linguistic comprehension skills in first and second grade to third grade reading comprehension. Linguistic comprehension and the interaction between linguistic comprehension and code-related skills each explained substantial variation in reading comprehension. Among students with low reading comprehension, more than 80% demonstrated weaknesses in linguistic comprehension alone, whereas approximately 15% demonstrated weaknesses in both linguistic comprehension and code-related skills. Results were remarkably similar for the language minority learners and native English speakers, suggesting the importance of their shared socioeconomic backgrounds and schooling contexts. PMID- 22293685 TI - The reading efficiency model: an extension of the componential model of reading. AB - The purpose of the present study was twofold: First, the authors investigated if an extended version of the component model of reading (CMR; Model 2), including decoding rate and oral vocabulary comprehension, accounted for more of the variance in reading comprehension than the commonly used measures of the cognitive factors in the CMR. Second, the authors investigated the fitness of a new model, titled the reading efficiency model (REM), which deviates from earlier models regarding how reading is defined. In the study, 780 Norwegian students from Grades 6 and 10 were recruited. Here, hierarchical regression analyses showed that the extended model did not account for more of the variance in reading comprehension than the traditional CMR model (Model 1). In the second part of the study the authors used structural equation modeling (SEM) to explore the REM. The results showed that the REM explained an overall larger amount of variance in reading ability, compared to Model 1 and Model 2. This result is probably the result of the new definition of reading applied in the REM. The authors believe their model will more fully reflects students' differentiated reading skills by including reading fluency in the definition of reading. PMID- 22293686 TI - Cognitive component of componential model of reading applied to different orthographies. AB - Whether the simple view of reading (SVR) as incorporated in the componential model of reading (CMR) is applicable to other orthographies than English was explored in this study. Spanish, with transparent orthography and Chinese, with opaque orthography were selected because of their diverse characteristics. The first part reports a study of students from grades 2 and 3, whose home language and medium of instruction was Spanish, and were administered tests of decoding, listening, and reading comprehension. A comparison group of 49 children from Grade 2, 54 children from Grade 3, and 55 children from Grade 4, whose home language and instruction was English, were also administered tests of decoding, listening, and reading comprehension. Multiple regression analysis showed that approximately 60% of the variance in reading comprehension of Spanish participants and 50% of the variance in reading comprehension of English participants were explained by decoding and listening comprehension. Furthermore, the performance of third grade Spanish participants resembled that of fourth grade English-speaking participants. In the second study, 102 Chinese students from Grade 2 and 106 students from Grade 4 were administered tasks of Chinese character recognition, reading fluency, listening, and reading comprehension. Multiple regression analyses showed character recognition and listening comprehension accounted for 25% and 42% of the variance in Chinese reading comprehension at Grades 2 and 4 respectively. These results indicate that the simple view of reading is applicable to writing systems other than that of English. PMID- 22293687 TI - Improved access to life insurance after genetic diagnosis of familial hypercholesterolaemia: cross-sectional postal questionnaire study. AB - A decade ago, in the initial stage of genetic testing for familial hypercholesterolaemia (FH) in The Netherlands, it was reported that such screening decreased access to affordable life insurance for mutation carriers. In 2003, in order to improve access to insurance for FH mutation carriers, insurers agreed to underwrite according to a set of guidelines. In this cross-sectional study, we assessed whether access to insurance has improved since the advent of these guidelines. We approached 2825 subjects that had participated in the genetic testing for FH between 1998 and 2003. We compared unconditional acceptance rates before and after FH diagnosis and before and after the guidelines were issued by means of logistic regression analysis. Our study outcome pertains to 414 FH patients who applied for life insurance. Unconditional acceptance of a policy before DNA diagnosis and before the issue of guidelines occurred in 182 out of 255 (71%) cases, versus 27 out of 35 (77%) cases after DNA diagnosis, but before the issue of guidelines. De facto, 107 out of 124 (86%) patients received unconditional acceptance after DNA diagnosis and after the issue of guidelines (P for trend=0.002). Access to life insurance improved for FH patients after molecular diagnosis and it improved even further after the guidelines were issued. Therefore, we argue that limited access to life insurance on the basis of 'DNA discrimination' is no longer a valid argument against genetic cascade testing for FH, at least not in our country. PMID- 22293688 TI - 1000 Genomes-based imputation identifies novel and refined associations for the Wellcome Trust Case Control Consortium phase 1 Data. AB - We hypothesize that imputation based on data from the 1000 Genomes Project can identify novel association signals on a genome-wide scale due to the dense marker map and the large number of haplotypes. To test the hypothesis, the Wellcome Trust Case Control Consortium (WTCCC) Phase I genotype data were imputed using 1000 genomes as reference (20100804 EUR), and seven case/control association studies were performed using imputed dosages. We observed two 'missed' disease associated variants that were undetectable by the original WTCCC analysis, but were reported by later studies after the 2007 WTCCC publication. One is within the IL2RA gene for association with type 1 diabetes and the other in proximity with the CDKN2B gene for association with type 2 diabetes. We also identified two refined associations. One is SNP rs11209026 in exon 9 of IL23R for association with Crohn's disease, which is predicted to be probably damaging by PolyPhen2. The other refined variant is in the CUX2 gene region for association with type 1 diabetes, where the newly identified top SNP rs1265564 has an association P-value of 1.68 * 10(-16). The new lead SNP for the two refined loci provides a more plausible explanation for the disease association. We demonstrated that 1000 Genomes-based imputation could indeed identify both novel (in our case, 'missed' because they were detected and replicated by studies after 2007) and refined signals. We anticipate the findings derived from this study to provide timely information when individual groups and consortia are beginning to engage in 1000 genomes-based imputation. PMID- 22293689 TI - An evaluation of different meta-analysis approaches in the presence of allelic heterogeneity. AB - Meta-analysis has proven a useful tool in genetic association studies. Allelic heterogeneity can arise from ethnic background differences across populations being meta-analyzed (for example, in search of common frequency variants through genome-wide association studies), and through the presence of multiple low frequency and rare associated variants in the same functional unit of interest (for example, within a gene or a regulatory region). The latter challenge will be increasingly relevant in whole-genome and whole-exome sequencing studies investigating association with complex traits. Here, we evaluate the performance of different approaches to meta-analysis in the presence of allelic heterogeneity. We simulate allelic heterogeneity scenarios in three populations and examine the performance of current approaches to the analysis of these data. We show that current approaches can detect only a small fraction of common frequency causal variants. We also find that for low-frequency variants with large effects (odds ratios 2-3), single-point tests have high power, but also high false-positive rates. P-value based meta-analysis of summary results from allele-matching locus-wide tests outperforms collapsing approaches. We conclude that current strategies for the combination of genetic association data in the presence of allelic heterogeneity are insufficiently powered. PMID- 22293690 TI - Two families with sibling recurrence of the 17q21.31 microdeletion syndrome due to low-grade mosaicism. AB - The 17q21.31 microdeletion syndrome is characterised by intellectual disability, epilepsy, distinctive facial dysmorphism, and congenital anomalies. To date, all individuals reported with this syndrome have been simplex patients, resulting from de novo deletions. Here, we report sibling recurrence of the 17q21.31 microdeletion syndrome in two independent families. In both families, the mother was confirmed to be the parent-of-origin for the 17q21.31 deletion. Fluorescence in situ hybridisation analyses in buccal mucosa cells, of the mother of family 1, identified monosomy 17q21.31 in 4/50 nuclei (8%). In mother of family 2, the deletion was identified in 2/60 (3%) metaphase and in 3/100 (3%) interphase nuclei in peripheral lymphocytes, and in 7/100 (7%) interphase nuclei in buccal cells. A common 17q21.31 inversion polymorphism predisposes to non-allelic homologous recombination and hereby to the 17q21.31 microdeletion syndrome. On the basis of the 17q21.31 inversion status of the parents, we calculated that the probability of the second deletion occurring by chance alone was 1/14,438 and 1/4812, respectively. If the inversion status of the parents of a child with the 17q21.31 microdeletion syndrome is unknown, the overall risk of a second child with the 17q21.31 microdeletion is 1/9461. We conclude that the presence of low level maternal somatic-gonadal mosaicism is associated with the microdeletion recurrence in these families. This suggests that the recurrence risk for parents with a child with a 17q21.31 microdeletion for future pregnancies is higher than by chance alone and testing for mosaicism in the parents might be considered as a helpful tool in the genetic counselling. PMID- 22293691 TI - [Challenges of young pharmaceutical researchers aiming for the drug and pharmacological development for therapeutical strategy by using pathological models and evaluation of drug efficacy]. PMID- 22293692 TI - [Influence of nerve growth factor (NGF) on distribution of perivascular nerves in tumor neovasculatures of mouse corneal]. AB - Angiogenesis, or new blood vessel formation, is critical for the growth and spread of tumors. The vascular tone and tissue blood flow are maintained and regulated by perivascular nerves. However, many studies have reported that tumor neovascular vessels have no innervation of perivascular nerves. We have shown that nerve growth factor (NGF) facilitated perivascular innervation and suppressed the tumor growth. From these results, we hypothesized that the neuronal regulation of blood flow toward tumors via perivascular nerves may lead suppression of the tumor growth. Therefore, the aim of this study is to investigate effect of NGF on distribution of perivascular nerves and neovessel form in tumor tissues, which were generated by mouse corneal micropocket method. A gel, which contained DU145 prostate carcinoma cells, was implanted into the mouse corneal. NGF or saline was subcutaneously administered using an osmotic mini-pump. After 1 week, the distribution of perivascular nerves in mouse corneal were immunohistochemically studied. Also, the density of neovessels (immunocytochemically stained CD31) and smooth muscles (alpha-smooth muscle actin; SMA) in tumor tissues was quantified by the computer-assisted image processing. Four days after implantation of tumor cells in mouse corneal, many neovessels generated from corneal limbal vessels were observed in tumor tissues. Treatment of mouse with NGF resulted in innervation of perivascular nerves around tumor neovessels, but not observed in saline-treated group. NGF treatment increased SMA-, but not CD31-, immunopositive cells. These results suggest that NGF may facilitate innervations of perivascular nerve to regulate the blood flow in tumor neovessels. PMID- 22293693 TI - [Altered intestinal P-glycoprotein expression levels affect pharmacodynamics under diabetic condition]. AB - P-glycoprotein (P-gp), one of the important drug-efflux pumps, is known to affect pharmacokinetics and pharmacodynamics of P-gp substrate drugs. We have previously reported that intestinal P-gp expression levels are transiently decreased in streptozotocin (STZ)-induced type 1 diabetic mouse model. Herein, we examined the analgesic effects of orally administered morphine and its pharmacokinetic properties under diabetic conditions, specifically focusing on the involvement of intestinal P-gp in a type 1 diabetic mouse model. Type 1 diabetes was induced in male ddY mice by an i.p. injection of STZ (230 mg/kg). We assessed the oral morphine analgesia using the tail-flick test. Serum and brain morphine content were determined on a HPLC-ECD system. Intestinal P-gp expression levels were significantly decreased on day 9 after STZ administration. On the other hands, oral morphine analgesia, and serum and brain morphine content were significantly increased on day 9 after STZ administration. The decrease in the intestinal P-gp expression levels were suppressed by aminoguanidine, a specific iNOS inhibitor. Interestingly, the increase in the analgesic effect of morphine, as well as serum and brain morphine content, was suppressed by aminoguanidine. Conversely, there was no change in the analgesic effect obtained with subcutaneous morphine in STZ treated mice. In conclusions, our findings suggest that the oral morphine analgesia is dependent on intestinal P-gp expression, and that may be one of the problems against obtaining stable pharmacological effects of morphine in diabetic patients. PMID- 22293694 TI - [Cardioprotective effect of fluvoxamine, sigma-1 receptor high affinity agonist]. AB - Selective serotonin reuptake inhibitors (SSRIs) are known to reduce post myocardial infarction (MI)-induced morbidity and mortality. However, the molecular mechanism underlying SSRI-induced cardioprotection remains unclear. Here, we investigated the role of sigma-1 receptor (Sig-1R) stimulation with fluvoxamine on myocardial hypertrophy and cardioprotection. Male ICR mice were subjected to transverse aortic constriction (TAC) in the cardiac aortic arch. To confirm the cardioprotective role of Sig-1R stimulation by fluvoxamine, we treated mice with fluvoxamine (0.5 or 1 mg/kg) orally once a day for 4 weeks after onset of aortic banding. Interestingly, in untreated mice, Sig-1R expression in the left ventricle (LV) markedly decreased over 4 weeks with increased hypertrophy. By contrast, fluvoxamine administration significantly attenuated TAC-induced myocardial hypertrophy concomitant with recovery of Sig-1R expression in LV. Fluvoxamine also attenuated hypertrophy-induced impaired LV fractional shortening. The fluvoxamine cardioprotective effect was nullified by treatment with a Sig-1R antagonist, NE-100 (1 mg/kg). Importantly, another SSRI with very low affinity for Sig-1R, paroxetine, did not exhibit antihypertrophic effects in TAC mice and in cultured cardiomyocyte treated with angiotensin II. Fluvoxamine treatment significantly restored TAC-induced impaired Akt and eNOS phosphorylation in LV. Our findings suggest that fluvoxamine protects heart against TAC-induced cardiac dysfunction via upregulation of Sig-1R and stimulation of Sig-1R-mediated Akt-eNOS signaling in mice. This is the first report of a potential role of Sig-1R stimulation by fluvoxamine in preventing cardiac hypertrophy and myocardial injury in TAC mice. PMID- 22293695 TI - [Investigation on the mechanisms for the suppression of cell proliferation in the dentate gyrus of the hippocampus in ACTH treated rats]. AB - We previously reported that adrenocorticotropic hormone (ACTH)-treated rats serve as a valuable animal model for tricyclic antidepressant-resistant depressive conditions. The present study was undertaken to investigate the changes in neurogenesis in the hippocampus of ACTH-treated rats. Chronic treatment of ACTH decreased the number of bromodeoxyuridine-labeled cells in the dentate gyrus, and the coadministration of imipramine and lithium, and electroconvulsive stimuli recovered these reductions. Furthermore, chronic ACTH treatment also decreased the expression of brain-derived neurotrophic factor, and the coadministration of imipramine and lithium, and electroconvulsive stimuli recovered these reductions. These results suggest that antidepressant-resistant depression is caused by the suppression of neurogenesis, and the coadministration of imipramine and lithium, and electroconvulsive stimuli exert an antidepressant-like effect by recovering proliferative signals and neurogenesis. PMID- 22293696 TI - [Impaired memory following repeated pentylenetetrazol treatments in kindled mice]. AB - Epilepsy is characterized by recurrent seizures, which are caused by excessive discharges from cerebral neurons. Currently, antiepileptic drugs that possess sodium channel blocking activities and also mediate GABA-ergic systems are primarily used to prevent epileptic seizure. However, approximately 40% of patients with epilepsy suffer from interictal psychiatric comorbidities in clinical practice. Furthermore, it is unclear whether epilepsy is associated with psychic function. The aim of the present study was to clarify the effects of kindling-induced epileptic seizures on psychic functioning using behavioral pharmacological tests. Pentylenetetrazol (PTZ)-kindled mice demonstrated no significant differences in locomotor activity and muscle relaxation compared with naive mice. PTZ-kindled mice also demonstrated cognitive impairment in the objective location test, but no significant effects of PTZ-kindling were observed in the Y-maze test. These findings suggested that PTZ-kindling impairs reference memory, but not working memory. These results suggest that, with respect to their psychic functioning, PTZ-kindled mice have specific characteristics. PMID- 22293697 TI - [Challenges for futuristic nanomedical detection, diagnosis and treatment]. PMID- 22293698 TI - [Structural analysis of proteins in living eukaryotic cells using magnetic resonance spectroscopy]. AB - Three-dimensional structures of proteins are often critical in understanding proteins functions. However, structures or states of proteins in cells undergo dynamical changes in response to interactions with other proteins and/or biological molecules. In addition, post-translational modification such as phosphorylation, methylation and ubiquitination can drastically change the structure and hence the properties of proteins. Therefore, to precisely correlate structure data of proteins with cell biology data, the structure information should be collected in living cells preferably at atomic level. In addition, as numerous biomolecules are packed into limited space, the concentration of macromolecules is substantially high in cells. Such crowded environment of the cell interior can markedly change proteins behavior, affecting biochemistry and biophysics of the proteins, which is so-called "Macromolecular Crowding Effect". To figure out protein behavior inside cells, which may be missed in in vitro studies, we are developing NMR and ESR methodologies to analyze protein structure and dynamics inside eukaryotic cultured cells. In this paper, in-cell NMR/ESR studies performed on HeLa cells and Xenopus oocytes are presented. PMID- 22293699 TI - [Development of specific protein labeling method by using small molecular probes]. AB - Selective protein labeling with a small molecular probe is a versatile method for elucidating protein functions in living cells. In this review, we report a new protein labeling method that enables selective covalent modification of a tag fused protein with small functional molecules. This method utilizes the specific interaction and rapid reaction between a short peptide tag and a molecular probe, which comprises the cysteine-containing short CA6D4x2 tag (CAAAAAADDDDGDDDD) and a tetranuclear Zn(II)-DpaTyr probe containing a reactive alpha-chloroacetyl moiety. This labeling system, so-called reactive tag system, was successfully applied to the fluorescence imaging of tag-fused GPCRs such as bradykinin receptor (B2R) and acetylcholine receptor (m1AchR) expressing on HEK293 cells. The utility of this labeling method was demonstrated in the function analyses of GPCRs, such as fluorescence visualization of the stimuli-responsive internalization of GPCRs and pH change in endosomes containing the internalized GPCRs. PMID- 22293700 TI - [Development of photodegradable nanoparticle for phototherapy]. AB - Proteins have several remarkable advantages over conventional chemical catalysts. For these reasons, proteins are widely used in many fields. We have developed a hydrogel-based protein immobilization scheme that allows proteins to maintain their activity for a long period of time. Recently, we developed a photodegradable hydrogel and used it to control the biological activities of proteins. Protein activity is restricted when the protein is encapsulated within the gel, and the activity is restored when the protein is released from the gel by UV irradiation. It is expected that the drug delivery using the photodegradable hydrogel and phototherapy is a good combination for therapy of psoriasis vulgaris. PMID- 22293701 TI - [Development of bioanalytical techniques using micro- and nanostructures for medical applications]. AB - Micro- and nanobiodevices, which utilize micro- and nanospace corresponding in size to various biomolecules, are currently accelerating research on medical diagnosis and regenerative medicine. Moreover, novel analytical techniques beyond the past limitations are developed utilizing micro- and nanospace and are achieving an innovation from basic research to clinical diagnosis and therapy. We have developed nanopillar and nanowall array structures for a single molecule measurement and separation sciences, and then, demonstrated unique analytical techniques specific to a precisely defined nanospace. Physicochemical and biological approaches were adopted to understand nanofluidics in these nanospaces and interesting phenomena were found. We are also trying to transfer these micro- and nanodevices to clinical practices. Some examples such as a blood plasma separation device, a therapeutic drug monitoring device, an immuno-pillar device for high-speed and high-sensitivity cancer and disease markers are described in this paper. PMID- 22293702 TI - [New insights into the molecular mechanisms of lymphangiogenesis and pathophysiology]. AB - Lymphatic vessels play crucial roles in transporting tissue fluid and macromolecules, and in promoting tissue immune response. Recent studies have identified new lymphatic vessel growth in pathological conditions such as cancer progression. In fact, our experimental animal models revealed that tumors can induce lymphangiogenesis not only in primary sites, but in their draining lymph nodes (LNs), even before tumors get metastasized. In fact, lymphangiogenesis in draining lymph nodes leads to increased cancer spread to distant LNs and beyond. Importantly, we very recently identified that nodal lymphangiogenesis occurs in human skin cancers, and plays a significant role in promoting distant metastases resulting in reduced patient survival. Therefore, lymphangiogenesis could be a novel indicator and therapeutic target for the prevention of cancer metastasis. Recent advances in clarifying the functional role of lymphatic vessels began with the molecular identification of genes which are specifically expressed by the lymphatic endothelial cells. Lymphatic vessels arise from veins. Prox1, a homeobox transcription factor, specifies the lymphatic identity from venous endothelial cells. Thus, Prox1 is a master regulator of lymphatic vessel development. Vascular endothelial growth factor-C and its specific receptor VEGFR 3 compose an essential signal pathway for lymphatic vessel growth in physiological and pathological conditions. Furthermore, podoplanin, another transmembrane protein in lymphatic vessels is required for their separation from veins by activating CLEC2, the specific ligand in platelets, leading to thrombus formation between veins and lymphatic vessels. Moreover, recent progress in nano scale technologies enabled to visualize lymphatic vessels and quantitate their transport, leading to new approaches for nano-based medicine. PMID- 22293703 TI - [Survey on junior high school student's attitudes toward rational drug use and the educational effect by school pharmacists]. AB - The educational intervention could improve knowledge about rational drug use in the junior high school. Improving knowledge about rational drug use at an early age may be a good way to increase the population's awareness of health, medicines and self-medication. To educate the rational drug use, it is desirable that the school pharmacists participate in this educational program in the junior high school. So we conducted an educational lecture by school pharmacists to promote rational drug use and self-medication in junior high school students. The study compared participant responses before and after a lecture. After the first questionnaire, we lectured the mentioned above to them. Afterward, second questionnaire was conducted. In the second questionnaire, more than 95% of the students understood the contents of the lecture to some extent. After a lecture, students who answered that 'I don't have confidence that I can buy medicines rightly by myself' decreased from 42.7% to 11.7%. And students who answered that 'I don't have confidence that I can use medicines rightly by myself' decreased from 25.2% to 12.6%. It was possible to achieve a favorable modification of attitudes to rational use of medicines in junior high school students. Continuous interventions might allow better effects and could help to fill the gap in health education of the general population. PMID- 22293704 TI - [Change in the drug release behavior of theophylline sustained-release tablets after division into two halves]. AB - Dividing a tablet into two halves and providing them to patients is a routine approach in clinical practice. Obviously, the drug release behavior of tablets should be constant, regardless of the dividing process. Here, we investigated the change in drug release behavior after dividing tablets into two halves. Five commercial theophylline sustained-release tablets designed to be taken once a day were used as test tablets (two original products and three generic products). A 24 h dissolution test was performed for each tablet, and changes in drug release behavior were evaluated using similarity factors, f2, calculated from the drug release profiles. The drug release rates were substantially increased by dividing the tablets into two halves. Analysis of variance (ANOVA) revealed that the effect of the dividing process on drug release behavior was more significant than that of changing the products. We further observed the feature of cross sectioning of the surface of the tablets using a scanning electron microscope (SEM) and a laser-scanning microscope (LSM). The microscopic observations confirmed that the surface became rough and developed many cavities with the prolongation of the duration of the dissolution test. This study clarified that the division of tablets into two halves exerts significant effects on their drug release behavior, and may offer a profound insight into the proper use of pharmaceutical products. PMID- 22293705 TI - [Examination of factors affecting adverse reactions and dosage reduction in UGT1A1 genotyped patients: a retrospective survey of irinotecan]. AB - Our aim was to clarify the side effects of irinotecan which occurred in patients admitted to Showa University Hospital to investigate whether the UGT1A1 genetic polymorphism status was reflected in the discontinuation or dose reduction of irinotecan. We retrospectively investigated UGT1A1 genetic polymorphisms, irinotecan dosage, dose discontinuance or reduction, and laboratory results from May 1 2009 to April 30 2010. The analysis of UGT1A1 genetic polymorphisms in 23 patients showed that frequencies of the UGT1A1*6 and UGT1A1*28 polymorphisms were 35% (eight patients) and 22% (five patients), respectively, and 17% (three patients) were UGT1A1*6/UGT1A1*28 compound heterozygotes. Of all patients who received irinotecan, dose reduction occurred in six patients (38%) and discontinuance in two patients (13%) due to neutropenia and other factors. Of these eight patients, seven (88%) had the UGT1A1*6 and/or *28 polymorphism. The most common irinotecan dose reduction was about 25% of the initial dose. Grade 4 neutropenia was observed in two patients who had the UGT1A1*6 and/or *28 mutation (13%), and one patient was a compound heterozygote. Our investigation confirmed that the UGT1A1 genetic polymorphism status of the patients was reflected in the discontinuance or dose reduction of irinotecan. Our results suggest that Grade 4 neutropenia may occur in patients who are compound heterozygotes and that these patients may need careful selection of treatment regimens possibly involving discontinuance or reduction in irinotecan dosage. PMID- 22293706 TI - [Shortening of donepezil-induced QTc prolongation with a change in the interacting drug, after electrocardiograph monitoring by community pharmacists: a case report]. AB - We used a mobile electrocardiograph to manage the adverse effects and interactions of drugs, especially QT-prolonging drugs, in a community pharmacy setting. We report the case of a patient in whom the risk of drug-induced torsades de pointes (TdP) was lowered, after monitoring by community pharmacists. CASE: An 80-year-old woman was under donepezil (5 mg/d) therapy for Alzheimer's disease and also taking other drugs that interact with donepezil, namely, benidipine (8 mg/d) and atorvastatin (10 mg/d). The patient was visited almost every month, and an electrocardiogram was usually obtained. QTc prolongation (avg. 470+/-9 ms) was observed in the first to third tests. Her doctor was informed about these results and the risk factors (advanced age, gender, and drugs interactions (benidipine and atorvastatin)) associated with TdP and asked to respond promptly since several cases of donepezil-induced TdP have been reported. As a result, benidipine was replaced with amlodipine, while the remaining drugs were continued. After the change, a significant decrease in QTc values were observed in the fourth to seventh tests (avg. 441+/-9 ms, p=0.010), thereby indicating a decrease in TdP risk. The Drug Interaction Probability Scale (object drug, donepezil; precipitant drug, benidipine) score was +6 (probable). Thus, QTc shortening was a result of differences in donepezil-benidipine and donepezil-amlodipine interactions. PMID- 22293707 TI - [Enhancement of regulatory T cell induction by intravenous S-sulfonated Immunoglobulin during the treatment of experimental autoimmune encephalomyelitis]. AB - Intravenous immunoglobulin (IVIg) has been shown to be effective for a variety of autoimmune diseases. Despite its widespread use and therapeutic success, the precise mechanisms for the anti-inflammatory therapeutic effects of IVIg are not well understood. In particular, few reports have examined the mechanism of IVIg on regulatory T cells (Treg: CD4(+)CD25(+)FoxP3(+) T cells). In the present study, to clarify the effect of intravenous S-sulfonated immunoglobulin (S-IVIg) on Treg, we investigated experimental autoimmune encephalomyelitis (EAE), the representative animal model of autoimmune disease. First, when we evaluated the effect of S-IVIg in an acute EAE model, the prophylactic treatment of S-IVIg dose dependently controlled the symptoms of EAE. Next, we measured Treg in EAE mice spleen by flow cytometry. The percentage of Treg in S-IVIg-treated mice was significantly increased compared with Saline-treated mice. Finally, in reinduced EAE, S-IVIg not only prevented EAE progression, but also increased the percentage of Treg in the spleen. The increase in percentage of Treg in S-IVIg-treated EAE might be associated with protection against EAE. These observations provide important evidence that IVIg is effective in T-cell-mediated control of autoimmunity. PMID- 22293708 TI - Elastic properties of thin poly(vinyl alcohol)-cellulose nanocrystal membranes. AB - In spite of extensive studies on the preparation and characterization of nanocomposite materials, the correlation of their properties at the nanoscale with those in bulk is a relatively unexplored area. This is of great importance, especially for materials with potential biomedical applications, where surface properties are as important in determining their applicability as bulk characteristics. In this study, the nanomechanical characteristics of thin poly(vinyl alcohol) (PVOH)-poly(acrylic acid) (PAA)-cellulose nanocrystal (CNC) membranes were studied using the nanoindentation module in an atomic force microscope (AFM) and the properties were compared with the macro-scale properties obtained by tensile tests. In general, the elastic properties measured by nanoindentation followed the same trend as macro-scale tensile tests except for the PVOH 85-PAA 0-CNC 15 sample. In comparison to the macro-scale elastic properties, the measured elastic moduli with AFM were higher. Macro-scale tensile test results indicated that, in the presence of PAA, incorporation of CNCs up to 20 wt% improved the elastic modulus of PVOH, but when no PAA was added, increasing the CNC content above 10 wt% resulted in their agglomeration and degradation in mechanical properties of PVOH. The discrepancy between macro-scale tensile tests and nanoindentation in the PVOH 85-PAA 0-CNC 15 sample was correlated to the high degree of inhomogeneity of CNC dispersion in the matrix. It was found that the composites reinforced with cellulose nanocrystals had smaller indentation imprints and the pile-up effect increased with the increase of cellulose nanocrystal content. PMID- 22293709 TI - Relationship between inpatient satisfaction and nurse absenteeism: an exploratory study using WHO-PATH performance indicators in France. AB - BACKGROUND: Indicators describing results of care are widely explored in term of patient satisfaction (PS). Among factors explaining PS, human resources indicators have been studied in terms of burnout or job satisfaction among healthcare professionals. No research work has set out to explore the effect of absenteeism on PS scores. The objective of this study was to explore interaction between rate of absenteeism among nurses and PS results. METHODS: France has taken part in a project named PATH (Performance Assessment Tool for Hospitals) of the World Health Organization, aiming to develop a tool for the assessment of hospital performance. In the first semester 2008, 25 volunteering short-stay hospitals (teaching, general and private) provide complete data on nurse short absenteeism (periods of up to 7 consecutive days of sick leave) and on PS (a cross-sectional postal survey using a standardized validated French-language scale EQS-H exploring "quality of medical information" (MI) and "relationships with staff and daily routine" (RS)). A multi-level model was used to take into account of the hierarchical nature of the data. RESULTS: Two thousand and sixty five patients responded to the satisfaction questionnaire (participation rate: 40.9%). The mean age of respondents was 58 yrs (+/- 19), 41% were men. The mean duration of hospitalisation was 7.5 days (+/- 11.1). The mean absenteeism rate for nurses was 0.24% (+/- 0.14).All the PS scores were significantly and negatively correlated with rate of short-absenteeism among nurses (MI score: rho = -0.55, p < 0.01), RS score rho = -0.47, p = 0.02). The mixed model found a significant relationship between rate of absenteeism among nurses and PS scores (MI: p = 0.027; RS: p = 0.017). CONCLUSION: Results obtained in this study show that short-term absenteeism among nurses seems to be significantly and negatively correlated with PS. Our findings are an invitation to deepen our understanding of the impact of human resources on PS and to develop more specific projects. PMID- 22293711 TI - Lanthanide-binding peptides with two pendant aminodiacetate arms: impact of the sequence on chelation. AB - Lanthanide complexes with a series of hexapeptides-incorporating two unnatural chelating amino acids with aminodiacetate groups, Ada(1) and Ada(2)-have been examined in terms of their speciation, structure, stability and luminescence properties. Whereas Ada(2) acts as a tridentate donor in all cases, Ada(1) may act as a tetradentate donor thanks to the coordination of the amide carbonyl function assisted by the formation of a six-membered chelate ring. The position of the Ada(1) residue in the sequence is demonstrated to be critical for the lanthanide complex speciation and structure. Ada(1) promotes the coordination of the backbone amide function to afford a highly dehydrated Ln complex and an S shape structure of the peptide backbone, only when found in position 2. PMID- 22293712 TI - Studies on a novel class of triaryl pyridine N-glycosylamine amphiphiles as super gelators. AB - A novel class of six different triaryl pyridine N-glycosylamine amphiphiles was synthesised and characterized based on different spectral techniques, such as NMR and mass analysis. Gelation properties in different aromatic and aliphatic solvents were studied and gelation was observed predominantly in aliphatic solvents with CGC of 0.5% (w/v) and is attributed to the presence of long alkyl chain. All the gels thus obtained were studied using FE-SEM and powder XRD techniques which reveal fibrous entanglement of the molecules in the gel state with intermolecular spaces of 3.62 nm and 0.43 nm. PMID- 22293713 TI - Lapatinib, a dual inhibitor of EGFR and HER2, has synergistic effects with 5 fluorouracil on esophageal carcinoma. AB - Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) amplification occurs in over 30% of esophageal carcinomas. Combination therapies with EGFR and HER2-targeting agents and cytotoxic agents are considered a potential therapeutic option for esophageal cancer. We evaluated the antitumor effects of lapatinib, a dual tyrosine kinase inhibitor which simultaneously inhibits EGFR and HER2, 5-fluorouracil (5-Fu) alone and in combination on esophageal cancer cells. The antiproliferative activity of lapatinib, 5-Fu and lapatinib plus 5-Fu was measured by MTT assay and the combination index (CI) values were calculated. Additionally, cell cycle distribution of lapatinib alone and the combination with 5-Fu were detected by flow cytometry analysis. Annexin V-FITC and propidium iodide stain were used for analyzing the apoptotic cells after cells were treated with either agent alone or in combination. The EGFR and HER2 activated signaling pathways were monitored by western blotting. The combination of lapatinib and 5-Fu synergistically inhibited cell proliferation and exhibited an enhanced proapoptotic effect on esophageal cancer cells. The potentiation effect of combined treatment was associated with downregulation of EGFR and HER2 signaling pathways because data from western blot analysis showed that lapatinib in combination with 5-Fu markedly reduced the phosphorylation of EGFR and HER2, and inhibited the activation of downstream signaling molecules, such as AKT and ERK. A significant G1 arrest was also observed in cell cycle analysis after exposing cells to lapatinib, however, combination with 5-Fu did not enhance G1 arrest. These results indicate that the combination of the lapatinib and 5-Fu is a promising treatment option for esophageal carcinoma with HER2 amplification. PMID- 22293714 TI - Non-calcified coronary plaque volume inversely related to CD4(+) T-cell count in HIV infection. AB - BACKGROUND: Non-calcified coronary artery plaque (NCAP) might be an important predictor of cardiovascular events; however, few studies have directly measured NCAP in HIV-infected individuals. METHODS: We completed a prospective cross sectional evaluation of NCAP and coronary calcium scores using computed tomography angiography in HIV-infected patients (n=26) without known coronary artery disease (CAD), but who had one or more CAD risk factor(s), and compared them with controls matched on age, race, sex, body mass index and Framingham Risk Score (n=26). RESULTS: There was no difference in coronary calcium scores (114 +/ 218 versus 124 +/- 298; P=0.89) or NCAP volume (65 +/- 86 mm(3) versus 63 +/- 82 mm(3); P=0.38) between HIV-infected patients and controls, respectively. Among HIV-infected patients, lower CD4(+) T-cell count was associated with increased NCAP volume (r=-0.52, P=0.006). The CD4(+) T-cell count remained a significant predictor of NCAP in a multivariate analysis that adjusted for age and duration of antiretroviral therapy. CONCLUSIONS: Plaque burden is similar between HIV infected and uninfected individuals when matched on traditional CAD risk factors; however, immune function might mediate the development of atherosclerosis in HIV infection. PMID- 22293715 TI - Serum levels of CC chemokine receptor 4 and CXC chemokine receptor 3 ligands in CD8(+) Sezary syndrome. PMID- 22293716 TI - Case scenario: postoperative liver failure after liver resection in a cirrhotic patient. PMID- 22293718 TI - Choice of anesthetic combination determines Ca2+ leak after ischemia-reperfusion injury in the working rat heart: favorable versus adverse combinations. AB - BACKGROUND: There is a lack of studies investigating cardioprotection by common combinations of anesthetics. However, because a general anesthetic consists of a mixture of drugs with potentially interfering effects on signaling and cytoprotection, the most favorable combination should be used. METHODS: Working rat hearts were exposed to 20 min of ischemia and 30 min of reperfusion. Periischemic sevoflurane (2 vol-%), propofol (10 MUM), or remifentanil (3 nM) (single treatments) and the three combinations thereof (combination treatments) were assessed for their ability to improve postischemic left ventricular work and to prevent intracellular Ca leak and overload. Beat-to-beat oscillations in intracellular [Ca] were measured using indo-1 AM. Phosphorylation of calcium/calmodulin-dependent protein kinase IIdelta, ryanodine receptor-2, and phospholamban was determined. RESULTS: The single treatments with sevoflurane or remifentanil were highly protective with respect to functional recovery and Ca overload, but propofol, even at high concentrations, did not show similar protection. Sevoflurane combined with propofol completely lost its protection in the presence of low sedative propofol concentrations (>=1 MUM), whereas remifentanil combined with propofol (10 MUM) retained its protection. Propofol antagonism of sevoflurane protection was concentration-dependent and mimicked by the reactive oxygen species scavenger N-2-mercaptopropionyl-glycine. Addition of propofol to sevoflurane activated calcium/calmodulin-dependent protein kinase type IIdelta and hyperphosphorylated the ryanodine receptor-2, consistent with causing a postischemic Ca leak from the sarcoplasmic reticulum. Remifentanil did not enhance sevoflurane protection. CONCLUSIONS: The choice of anesthetic combination determines the postischemic Ca leak and intracellular overload. The results from these experiments will help to design studies for optimizing perioperative cardioprotection in high-risk surgical patients. PMID- 22293717 TI - Pulmonary hypertension in lambs transfused with stored blood is prevented by breathing nitric oxide. AB - BACKGROUND: During extended storage, erythrocytes undergo functional changes. These changes reduce the viability of erythrocytes leading to release of oxyhemoglobin, a potent scavenger of nitric oxide. We hypothesized that transfusion of ovine packed erythrocytes (PRBC) stored for prolonged periods would induce pulmonary vasoconstriction in lambs, and that reduced vascular nitric oxide concentrations would increase this vasoconstrictor effect. METHODS: We developed a model of autologous stored blood transfusion in lambs (n = 36). Leukoreduced blood was stored for either 2 days (fresh PRBC) or 40 days (stored PRBC). Fresh or stored PRBC were transfused into donors instrumented for awake hemodynamic measurements. Hemodynamic effects of PRBC transfusion were also studied after infusion of N-nitro-L-arginine methyl-ester (25 mg/kg) or during inhalation of nitric oxide (80 ppm). RESULTS: Cell-free hemoglobin levels were higher in the supernatant of stored PRBC than in supernatant of fresh PRBC (Mean +/- SD, 148 +/- 20 vs. 41 +/- 13 mg/dl, respectively, P < 0.001). Pulmonary artery pressure during transfusion of stored PRBC transiently increased from 13 +/- 1 to 18 +/- 1 mmHg (P < 0.001) and was associated with increased plasma hemoglobin concentrations. N-nitro-L-arginine methyl-ester potentiated the increase in pulmonary arterial pressure induced by transfusing stored PRBC, whereas inhalation of nitric oxide prevented the vasoconstrictor response. CONCLUSIONS: Our results suggest that patients with reduced vascular nitric oxide levels because of endothelial dysfunction may be more susceptible to adverse effects of transfusing blood stored for prolonged periods. These patients might benefit from transfusion of fresh PRBC, when available, or inhaled nitric oxide supplementation to prevent the pulmonary hypertension associated with transfusion of stored PRBC. PMID- 22293719 TI - Continuous femoral nerve blocks: decreasing local anesthetic concentration to minimize quadriceps femoris weakness. AB - BACKGROUND: Whether decreasing the local anesthetic concentration during a continuous femoral nerve block results in less quadriceps weakness remains unknown. METHODS: Preoperatively, bilateral femoral perineural catheters were inserted in subjects undergoing bilateral knee arthroplasty (n = 36) at a single clinical center. Postoperatively, right-sided catheters were randomly assigned to receive perineural ropivacaine of either 0.1% (basal 12 ml/h; bolus 4 ml) or 0.4% (basal 3 ml/h; bolus 1 ml), with the left catheter receiving the alternative concentration/rate in an observer- and subject-masked fashion. The primary endpoint was the maximum voluntary isometric contraction of the quadriceps femoris muscles the morning of postoperative day 2. Equivalence of treatments would be concluded if the 95% CI for the difference fell within the interval -20% 20%. Secondary endpoints included active knee extension, passive knee flexion, tolerance to cutaneous electrical current applied over the distal quadriceps tendon, dynamic pain scores, opioid requirements, and ropivacaine consumption. RESULTS: Quadriceps maximum voluntary isometric contraction for limbs receiving 0.1% ropivacaine was a mean (SD) of 13 (8) N . m, versus 12 (8) N . m for limbs receiving 0.4% [intrasubject difference of 3 (40) percentage points; 95% CI -10 17; P = 0.63]. Because the 95% CI fell within prespecified tolerances, we conclude that the effect of the two concentrations were equivalent. Similarly, there were no statistically significant differences in secondary endpoints. CONCLUSIONS: For continuous femoral nerve blocks, we found no evidence that local anesthetic concentration and volume influence block characteristics, suggesting that local anesthetic dose (mass) is the primary determinant of perineural infusion effects. PMID- 22293720 TI - Xenon attenuates hippocampal long-term potentiation by diminishing synaptic and extrasynaptic N-methyl-D-aspartate receptor currents. AB - BACKGROUND: The memory-blocking properties of general anesthetics are of high clinical relevance and scientific interest. The inhalational anesthetic xenon antagonizes N-methyl-D-aspartate (NMDA) receptors. It is unknown if xenon affects long-term potentiation (LTP), a cellular correlate for memory formation. In hippocampal brain slices, the authors investigated in area CA1 whether xenon affects LTP, NMDA receptor-mediated neurotransmission, and intracellular calcium concentrations. METHODS: In sagittal murine hippocampal brain slices, the authors investigated the effects of xenon on LTP by recording excitatory postsynaptic field potentials. Using fluorometric calcium imaging, the authors tested the influence of xenon on calcium influx during high-frequency stimulation. In addition, using the patch-clamp technique, the xenon effect on synaptic and extrasynaptic NMDA receptors and L-type calcium channels was examined. RESULTS: In the absence of xenon, high-frequency stimulation reliably induced LTP and potentiated field potential slopes to (mean +/- SEM) 127.2 +/- 5.8% (P < 0.001). In the presence of xenon, high-frequency stimulation induced only a short-term potentiation, and field potentials returned to baseline level after 15-20 min (105.9 +/- 2.9%; P = 0.090). NMDA receptor-mediated excitatory postsynaptic currents were reduced reversibly by xenon to 65.9 +/- 9.4% (P = 0.007) of control. When extrasynaptic receptors were activated, xenon decreased NMDA currents to 58.2 +/- 5.8% (P < 0.001). Xenon reduced the increase in intracellular calcium during high-frequency stimulation without affecting L-type calcium channels. CONCLUSIONS: N-methyl-D-aspartate receptor activation is crucial for the induction of CA1 LTP. Thus, the depression of NMDA receptor mediated neurotransmission presumably contributes to the blockade of LTP under xenon. Because LTP is assumed to be involved in learning and memory, its blockade might be a key mechanism for xenon's amnestic properties. PMID- 22293722 TI - Manganese oxide-catalyzed transformation of primary amines to primary amides through the sequence of oxidative dehydrogenation and successive hydration. AB - Manganese oxide octahedral molecular sieves (OMS-2) could act as an efficient, reusable heterogeneous catalyst for transformation of various primary amines to the corresponding primary amides through the sequence of oxidative dehydrogenation and successive hydration. PMID- 22293721 TI - Surgery and brain atrophy in cognitively normal elderly subjects and subjects diagnosed with mild cognitive impairment. AB - BACKGROUND: Structural magnetic resonance imaging is used to longitudinally monitor the progression of Alzheimer disease from its presymptomatic to symptomatic phases. Using magnetic resonance imaging data from the Alzheimer's Disease Neuroimaging Initiative, we tested the hypothesis that surgery would impact brain parameters associated with progression of dementia. METHODS: Brain images from the neuroimaging initiative database were used to study normal volunteer subjects and patients with mild cognitive impairment for the age group 55 to 90 inclusive. We compared changes in regional brain anatomy for three visits that defined two intervisit intervals for a surgical cohort (n = 41) and a propensity matched nonsurgical control cohort (n = 123). The first interval for the surgical cohort contained the surgical date. Regional brain volumes were determined with Freesurfer and quantitatively described with J-image software (University of California at San Francisco, San Francisco, California). Statistical analysis used Repeated Measures ANCOVA (SPSS, v.18.0; Chicago, IL). RESULTS: We found that surgical patients, during the first follow-up interval (5 9 months), but not subsequently, had increased rates of atrophy for cortical gray matter and hippocampus, and lateral ventricle enlargement, as compared with nonsurgical controls. A composite score of five cognitive tests during this interval showed reduced performance for surgical patients with mild cognitive impairment. CONCLUSIONS: Elderly subjects after surgery experienced an increased rate of brain atrophy during the initial evaluation interval, a time associated with enhanced risk for postoperative cognitive dysfunction. Although there was no difference in atrophy rate by diagnosis, subjects with mild cognitive impairment suffered greater subsequent cognitive effects. PMID- 22293723 TI - Effects of chronic chromate exposure on human serum prostate specific antigen: a cross sectional study. AB - The detrimental effect of chronic chromium (Cr) exposure on the prostate has never been studied. Here, we report the prostate specific antigen (PSA) changes in occupational chromate exposed workers. In this study, eighty six male occupational chromate exposed workers and forty five age-matched controls were recruited. The concentration of Cr in urine (U-Cr), serum total PSA (tPSA), free PSA (fPSA), high sensitive C reactive protein (Hs-CRP) and peripheral white blood cells count (WBC) were measured. The results show that the U-Cr, serum tPSA, Hs CRP and WBC were significantly higher in Cr exposed workers when compared to the controls. Contrastively, the serum fPSA level in Cr exposed workers was lower than controls. A significant positive correlation between U-Cr and serum tPSA was observed. Multiple linear regression analysis revealed that serum tPSA and fPSA level was statistically associated with the serum Hs-CRP and U-Cr concentration in Cr exposed workers. These observations suggested that chronic Cr exposure could produce potential prostate injury and the nonspecific inflammation at least might be one of the reasons to explain the elevated concentration of tPSA in chronic occupational chromate exposed workers. PMID- 22293724 TI - Flow and containment characteristics of an air-curtain fume hood operated at high temperatures. AB - The flow and leakage characteristics of the air-curtain fume hood under high temperature operation (between 100 degrees C and 250 degrees C) were studied. Laser-assisted flow visualization technique was used to reveal the hot plume movements in the cabinet and the critical conditions for the hood-top leakage. The sulfur hexafluoride tracer-gas concentration test method was employed to examine the containment spillages from the sash opening and the hood top. It was found that the primary parameters dominating the behavior of the flow field and hood performance are the sash height and the suction velocity as an air-curtain hood is operated at high temperatures. At large sash height and low suction velocity, the air curtain broke down and accompanied with three-dimensional flow in the cabinet. Since the suction velocity was low and the sash opening was large, the makeup air drawn down from the hood top became insufficient to counter act the rising hot plume. Under this situation, containment leakage from the sash opening and the hood top was observed. At small sash opening and high suction velocity, the air curtain presented robust characteristics and the makeup air flow from the hood top was sufficiently large. Therefore the containment leakages from the sash opening and the hood top were not observed. According to the results of experiments, quantitative operation sash height and suction velocity corresponding to the operation temperatures were suggested. PMID- 22293725 TI - Disparities of metabolic syndrome prevalence by age, gender and occupation among Korean adult workers. AB - Occupation can influence the prevalence of metabolic syndrome. Age and gender could interact with the association between occupation and metabolic syndrome. This study aimed to investigate the prevalence of metabolic syndrome among the Korean working population and determine whether the prevalence differed according to occupation, age and gender. We conducted a cross-sectional study in Korean adults using the Third Korean National Health and Nutrition Examination Survey (KNHANES III). The analysis included 3,288 workers over 19 yr old. The prevalence odds ratios (PORs) of metabolic syndrome among representative types of occupations were estimated after stratification for age and gender by logistic regression. Female manual workers had a higher prevalence of metabolic syndrome than female non-manual workers among those younger than age 50 (POR=1.95, 95%CI=1.12-3.40). However, female manual workers aged 50 and older had a lower prevalence of metabolic syndrome than female non-manual workers (POR=0.36, 95%CI=0.22-0.59). Manual occupations can be a risk factor for metabolic syndrome, but this correlation is limited to younger female workers. The effects of occupation on the prevalence of metabolic syndrome were different between older and younger workers, which could be due to longitudinal transition of socio cultural structure. PMID- 22293726 TI - Effects of sleep hygiene education and behavioral therapy on sleep quality of white-collar workers: a randomized controlled trial. AB - Because poor sleep quality can reduce quality of life and increase prevalence of illness in workers, interventions are becoming increasingly important for businesses. To evaluate how sleep quality is affected by one-on-one behavioral modification when combined with group education, we conducted a randomized, controlled trial among day-shift white-collar employees working for an information-technology service company in Japan. Participants were randomly allocated to groups receiving either sleep hygiene group education (control group), or education combined with individual sleep modification training (one-on one group). Occupational health professionals carried out both procedures, and sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). PSQI scores were obtained before and after the intervention period, and changes in scores were compared across groups after adjustments for age, gender, job title, smoking and drinking habits, body-mass index, and mental health as assessed using K6 scores. The average PSQI score for the control group decreased by 0.8, whereas that of the one-on-one group decreased by 1.8 (difference of 1), resulting in a significantly greater decrease in score for the one-on-one group (95% confidence interval: 0.02 to 2.0). These results show that, compared to sleep hygiene group education alone, the addition of individual behavioral training significantly improved the sleep quality of workers after only three months. PMID- 22293727 TI - Evaluation of exposure risk in the weaving process of MWCNT-coated yarn with real time particle concentration measurements and characterization of dust particles. AB - Various applications of multiwalled carbon nanotubes (MWCNT) have been developed. One of these applications is an efficient sheet heating element that is woven from MWCNT-coated yarn. In this research, we assessed the exposure to MWCNT and/or the probability of particle release from broken MWCNT-coated yarn during the weaving process. This was accomplished using particle concentrations, microscopic observation, and carbon analysis. In the weaving process, neither an increase in the number of particles nor a difference in particle-size distribution was observed. In the scanning electron micrographic observation, nanosize MWCNT particles were not detected, but there were micron-size particles containing MWCNT as fragments of the yarn. Carbon analysis showed the concentration of micron-size particles containing MWCNT did not exceed 0.0053 mg C/m(3) around the loom. This value was much lower than the respirable dust mass concentration. Most of micron-size particles seemed to originate from polyester yarn without MWCNT coating. It is recommended that workers use conventional (even not specialized for nanoparticles) personal protective equipment such as respirators and gloves to prevent exposure to respirable-size MWCNT-containing particles. The probability of MWCNT fall-off from the MWCNT-coated yarn was not detected by transmission electron microscopic observation of MWCNT-coated yarn before or after the weaving process. PMID- 22293728 TI - The characteristics of vibrotactile perception threshold among shipyard workers in a tropical environment. AB - The objectives of this study are to determine the prevalence of hand-arm vibration syndrome (HAVS) and the characteristics of the vibrotactile perception threshold (VPT) among users of hand-held vibrating tools working in a tropical environment. A cross sectional study was done among 47 shipyard workers using instruments and a questionnaire to determine HAVS related symptoms. The vibration acceleration magnitude was determined using a Human Vibration Meter (Maestro). A P8 Pallesthesiometer (EMSON-MAT, Poland) was used to determine the VPT of index and little finger at frequencies of 31.5 Hz and 125 Hz. The mean reference threshold shift was determined from the reference threshold shift derived from the VPT value. The results show a moderate prevalence of HAVS (49%) among the shipyard workers. They were exposed to the same high intensity level of HAVS (mean = 4.19 +/- 1.94 m/s(2)) from the use of vibrating hand-held tools. The VPT values were found to be higher for both fingers and both frequencies (index, 31.5 Hz = 110.91 +/- 7.36 dB, 125 Hz = 117.0 +/- 10.25 dB; little, 31.5 Hz = 110.70 +/ 6.75 dB, 125 Hz = 117.71 +/- 10.25 dB) compared to the normal healthy population with a mean threshold shift of between 9.20 to 10.61 decibels. The frequency of 31.5 Hz had a higher percentage of positive mean reference threshold shift (index finger=93.6%, little finger=100%) compared to 125 Hz (index finger=85.1%, little finger=78.7%). In conclusion, the prevalence of HAVS was lower than those working in a cold environment; however, all workers had a higher mean VPT value compared to the normal population with all those reported as having HAVS showing a positive mean reference threshold shift of VPT value. PMID- 22293729 TI - Isotopic response of graft versus host disease following herpes zoster infection: case report and review of the literature. PMID- 22293730 TI - Highly polarized single-c-domain single-crystal Pb(Mn,Nb)O(3)-PZT thin films. AB - In-plane unstrained single-c-domain/single-crystal thin films of PZT-based ternary ferroelectric perovskite, xiPb(Mn,Nb)O3-(1 - xi)PZT, were grown on SrRuO(3)/Pt/MgO substrates using magnetron sputtering followed by quenching. The sputtered unstrained thin films exhibit unique ferroelectric properties: high coercive field, Ec > 180 kV/cm, large remanent polarization, P(r) = 100 MUC/cm(2), small relative dielectric constants, epsilon* = 100 to 150, high Curie temperature, Tc = ~600 degrees C, and bulk-like large transverse piezoelectric constants, e31,f = -12.0 C/m(2) for PZT(48/52) at xi = 0.06. The unstrained thin films are an ideal structure to extract the bulk ferroelectric properties. Their micro-structures and ferroelectric properties are discussed in relation to the potential applications for piezoelectric MEMS. PMID- 22293731 TI - Multiferroic and fatigue behavior of BiFe(0.95)Mn(0.05)O3/Bi(0.90)La(0.10)Fe(0.85)Zn(0.15)O3 bilayered thin films. AB - Bilayered thin films consisting of BiFe(0.95)Mn(0.05)O(3) (BFMO) and Bi(0.90)La(0.10)Fe(0.85)Zn(0.15O3) (BLFZO) layers were prepared on Pt-coated silicon substrates without any buffer layers by RF sputtering. The (110) orientation was induced with a high phase purity for all bilayers as a result of the introduction of the bottom (110)-oriented BLFZO layer. The low leakage current density of BFMO/BLFZO bilayers could be attributed to a combined effect of the BFMO and BLFZO layers. The dielectric constant increases, the remanent polarization decreases, and the coercive field slightly increases with increasing thickness of the BLFZO layer in BFMO/BLFZO bilayers. Magnetic properties in BFMO/BLFZO bilayers are improved by increasing the BFMO layer thicknesses. A large polarization value of 2Pr ~ 189.5 MUC/cm2 is obtained for the BFMO/ BLFZO bilayer with a thickness ratio of 3:1, which is much larger than those reported for BFO-based single layers or multilayers, and a good fatigue behavior is demonstrated with an increase in measurement frequencies and driving electric fields. PMID- 22293732 TI - Quartz resonator instabilities under cryogenic conditions. AB - The phase noise of a quartz crystal resonator working at liquid helium temperatures is studied. Measurement methods and the device environment are explained. The phase noise is measured for different resonance modes, excitation levels, amount of operating time, device orientations in relation to the cryocooler vibration axis, and temperatures. Stability limits of a frequency source based on such devices are evaluated in the present measurement conditions. The sources of phase flicker and white noises are identified. Finally, the results are compared with previous works. PMID- 22293733 TI - An analysis of nonlinear vibrations of coupled thickness-shear and flexural modes of quartz crystal plates with the homotopy analysis method. AB - We investigated the nonlinear vibrations of the coupled thickness-shear and flexural modes of quartz crystal plates with the nonlinear Mindlin plate equations, taking into consideration the kinematic and material nonlinearities. The nonlinear Mindlin plate equations for strongly coupled thickness- shear and flexural modes have been established by following Mindlin with the nonlinear constitutive relations and approximation procedures. Based on the long thickness shear wave approximation and aided by corresponding linear solutions, the nonlinear equation of thickness-shear vibrations of quartz crystal plate has been solved by the combination of the Galerkin and homotopy analysis methods. The amplitude frequency relation we obtained showed that the nonlinear frequency of thickness-shear vibrations depends on the vibration amplitude, thickness, and length of plate, which is significantly different from the linear case. Numerical results from this study also indicated that neither kinematic nor material nonlinearities are the main factors in frequency shifts and performance fluctuation of the quartz crystal resonators we have observed. These efforts will result in applicable solution techniques for further studies of nonlinear effects of quartz plates under bias fields for the precise analysis and design of quartz crystal resonators. PMID- 22293734 TI - Ultrasound array transmitter architecture with high timing resolution using embedded phase-locked loops. AB - Coarse time quantization of delay profiles within ultrasound array systems can produce undesirable side lobes in the radiated beam profile. The severity of these side lobes is dependent upon the magnitude of phase quantization error--the deviation from ideal delay profiles to the achievable quantized case. This paper describes a method to improve interchannel delay accuracy without increasing system clock frequency by utilizing embedded phase-locked loop (PLL) components within commercial field-programmable gate arrays (FPGAs). Precise delays are achieved by shifting the relative phases of embedded PLL output clocks in 208-ps steps. The described architecture can achieve the necessary interelement timing resolution required for driving ultrasound arrays up to 50 MHz. The applicability of the proposed method at higher frequencies is demonstrated by extrapolating experimental results obtained using a 5-MHz array transducer. Results indicate an increase in transmit dynamic range (TDR) when using accurate delay profiles generated by the embedded-PLL method described, as opposed to using delay profiles quantized to the system clock. PMID- 22293735 TI - Harmonic reduction in capacitive micromachined ultrasonic transducers by gap feedback linearization. AB - The nonlinear relationship between the electrical input signal and electrostatic force acting on the capacitive micromachined ultrasonic transducer (CMUT) membrane limits its harmonic imaging performance. Several input shaping methods were proposed to compensate for the nonlinearity originating from the electrostatic force's dependence on the square of the applied voltage. Here, we analyze harmonic generation in CMUTs with a time-domain model. The model explains the basis of the input shaping methods and suggests that the nonlinearity resulting from gap dependence of the electrostatic force is also significant. It also suggests that the harmonic distortion in the output pressure can be eliminated by subharmonic ac-only excitation of the CMUT in addition to scaling the input voltage with the instantaneous gap. This gap feedback configuration can be approximated by the simple addition of a series impedance to the CMUT capacitance. We analyze several types of series impedance feedback topologies for gap feedback linearization. We show that for subharmonic ac excitation, although resistive and capacitive impedances result in a trade-off between input voltage and harmonic distortion for a desired pressure output, harmonic generation can be suppressed while increasing the Pa/V transmit sensitivity for proper series inductance and resistance feedback. We experimentally demonstrate the feedback method by reducing harmonic generation by 10 dB for the same output pressure at the fundamental frequency by using a simple series resistor feedback with a CMUT operating at a center frequency of 3 MHz. The proposed methods also allow for utilization of the full CMUT gap for transmit operation and, hence, should be useful in high-intensity ultrasonic applications in addition to harmonic imaging. PMID- 22293736 TI - Modeling ultrasound echoes in skin tissues using symmetric alpha-stable processes. AB - Starting from the widely accepted point-scattering model, this paper establishes, through analytical developments, that ultrasound signals backscattered from skin tissues converge to a complex Levy flight random process with non- Gaussian alpha stable statistics. The envelope signal follows a generalized (heavy-tailed) Rayleigh distribution. It is shown that these signal statistics imply that scatterers have heavy-tailed power-law cross sections. This model generalizes the Gaussian framework and provides a formal representation for a new case of non Gaussian statistics, in which both the number of scatterers and the variance of their cross sections tend to infinity. In addition, analytical expressions are derived to relate the alpha-stable parameters to scatterer properties. Simulations show that these expressions can be used as rigorous interpretation tools for tissue characterization. Several experimental results supported by excellent goodness-of-fit tests confirm the proposed analytical model. Finally, these fundamental results set the basis for new echography processing methods and quantitative ultrasound characterization tools. PMID- 22293737 TI - Power density of piezoelectric transformers improved using a contact heat transfer structure. AB - Based on contact heat transfer, a novel method to increase power density of piezoelectric transformers is proposed. A heat transfer structure is realized by directly attaching a dissipater to the piezoelectric transformer plate. By maintaining the vibration mode of the transformer and limiting additional energy losses from the contact interface, an appropriate design can improve power density of the transformer on a large scale, resulting from effective suppression of its working temperature rise. A prototype device was fabricated from a rectangular piezoelectric transformer, a copper heat transfer sheet, a thermal grease insulation pad, and an aluminum heat radiator. The experimental results show the transformer maintains a maximum power density of 135 W/cm(3) and an efficiency of 90.8% with a temperature rise of less than 10 degrees C after more than 36 h, without notable changes in performance. PMID- 22293738 TI - Laser generation of Lamb waves for defect detection: experimental methods and finite element modeling. AB - The propagation of Lamb waves generated by a pulsed laser beam in an aluminum sheet is modeled using finite element analysis, and the interaction with defects is studied and compared to experimental results. The ultrasonic Lamb waves are detected by an electromagnetic acoustic transducer (EMAT). The frequency content of the received wave is shown to be enhanced when the generation point is situated directly over the defect in both the modeled and experimental cases. Time-frequency analysis using a Wigner transform has enabled individual modes to be identified. PMID- 22293739 TI - A parallel-architecture parametric equalizer for air-coupled capacitive ultrasonic transducers. AB - Parametric equalization is rarely applied to ultrasonic transducer systems, for which it could be used on either the transmitter or the receiver to achieve a desired response. An optimized equalizer with both bump and cut capabilities would be advantageous for ultrasonic systems in applications in which variations in the transducer performance or the properties of the propagating medium produce a less-than-desirable signal. Compensation for non-ideal transducer response could be achieved using equalization on a device-by-device basis. Additionally, calibration of ultrasonic systems in the field could be obtained by offline optimization of equalization coefficients. In this work, a parametric equalizer for ultrasonic applications has been developed using multiple bi-quadratic filter elements arranged in a novel parallel arrangement to increase the flexibility of the equalization. The equalizer was implemented on a programmable system-on-chip (PSOC) using a small number of parallel 4th-order infinite impulse response switchedcapacitor band-pass filters. Because of the interdependency of the required coefficients for the switched capacitors, particle swarm optimization (PSO) was used to determine the optimum values. The response of a through transmission system using air-coupled capacitive ultrasonic transducers was then equalized to idealized Hamming function or brick-wall frequencydomain responses. In each case, there was excellent agreement between the equalized signals and the theoretical model, and the fidelity of the time-domain response was maintained. The bandwidth and center frequency response of the system were significantly improved. It was also shown that the equalizer could be used on either the transmitter or the receiver, and the system could compensate for the effects of transmitterreceiver misalignment. PMID- 22293740 TI - L-shaped piezoelectric motor--part I: design and experimental analysis. AB - This paper proposes an L-shaped piezoelectric motor consisting of two piezoelectric bimorphs of different lengths arranged perpendicularly to each other. The coupling of the bending vibration mode of the bimorphs results in an elliptical motion at the tip. A detailed finite element model was developed to optimize the dimensions of bimorph to achieve an effective coupling at the resonance frequency of 246 Hz. The motor was characterized by developing rotational and linear stages. The linear stage was tested with different friction contact surfaces and the maximum velocity was measured to be 12 mm/s. The rotational stage was used to obtain additional performance characteristics from the motor: maximum velocity of 120 rad/s, mechanical torque of 4.7 * 10-(5) N.m, and efficiency of 8.55%. PMID- 22293741 TI - L-shaped piezoelectric motor--part II: analytical modeling. AB - This paper develops an analytical model for an L-shaped piezoelectric motor. The motor structure has been described in detail in Part I of this study. The coupling of the bending vibration mode of the bimorphs results in an elliptical motion at the tip. The emphasis of this paper is on the development of a precise analytical model which can predict the dynamic behavior of the motor based on its geometry. The motor was first modeled mechanically to identify the natural frequencies and mode shapes of the structure. Next, an electromechanical model of the motor was developed to take into account the piezoelectric effect, and dynamics of L-shaped piezoelectric motor were obtained as a function of voltage and frequency. Finally, the analytical model was validated by comparing it to experiment results and the finite element method (FEM). PMID- 22293742 TI - A travelling wave rotary motor driven by three pairs of Langevin transducers. AB - In this work, numerical simulations and experimental measurements carried out on a high-power ultrasonic motor are presented. The proposed motor is composed of an annular shaped stator and two cone-shaped rotors. The rotors are pressed into contact with the edges of the inner surface of the stator by means of a pre stress system. A traveling rotating wave is generated in the stator by three pairs of Langevin transducers suitably shifted both in space and time. Each transducer is designed to excite radial nonaxisymmetric modes in the ring. The motor has been effectively clamped to the housing by using two flanges passing through the middle plane of 2 transducers. Finite element analysis was employed to evaluate two different configurations of the motor, both using 6 driving transducers, and to analyze the effect of the flange on the design and on the performance of the transducer. Experimental measurements carried out on a manufactured prototype show that the proposed motor exhibits greatly improved performance in terms of output torque and mechanical power compared with similar previous prototypes which use fewer driving transducers and a different clamping system. The motor weighed 0.67 kg, and had a working frequency of 23.6 kHz, maximum rotational speed of 116 rpm, and static torque of 0.94 Nm. PMID- 22293743 TI - Influence of crystal quality on the excitation and propagation of surface and bulk acoustic waves in polycrystalline AlN films. AB - We investigate the excitation and propagation of acoustic waves in polycrystalline aluminum nitride films along the directions parallel and normal to the c-axis. Longitudinal and transverse propagations are assessed through the frequency response of surface acoustic wave and bulk acoustic wave devices fabricated on films of different crystal qualities. The crystalline properties significantly affect the electromechanical coupling factors and acoustic properties of the piezoelectric layers. The presence of misoriented grains produces an overall decrease of the piezoelectric activity, degrading more severely the excitation and propagation of waves traveling transversally to the c axis. It is suggested that the presence of such crystalline defects in c-axis oriented films reduces the mechanical coherence between grains and hinders the transverse deformation of the film when the electric field is applied parallel to the surface. PMID- 22293744 TI - Radiation impedance and equivalent circuit for piezoelectric ultrasonic composite transducers of vibrational mode-conversion. AB - The piezoelectric ultrasonic composite transducer, which can be used in either gas or liquid media, is studied in this paper. The composite transducer is composed of a longitudinal sandwich piezoelectric transducer, a mechanical transformer, and a metal circular plate in flexural vibration. Acoustic radiation is produced by the flexural circular plate, which is excited by the longitudinal sandwich transducer and transformer. Based on the classic flexural theory of plates, the equivalent lumped parameters for a plate in axially symmetric flexural vibration with free boundary conditions are obtained. The radiation impedance of the plate is derived and the relationship between the radiation impedance and the frequency is analyzed. The equivalent circuits for the plate in flexural vibration and the composite transducer are given. The vibrational modes and the harmonic response of the composite piezoelectric transducer are simulated by the numerical method. Based on the theoretical and numerical analysis, two composite piezoelectric ultrasonic transducers are designed and manufactured, their admittance-frequency curves are measured, and the resonance frequency is obtained. The flexural vibrational displacement distribution of the transducer is measured with a laser scanning vibrometer. It is shown that the theoretical results are in good agreement with the measured resonance frequency and the displacement distribution. PMID- 22293745 TI - Design and characterization of dual-curvature 1.5-dimensional high-intensity focused ultrasound phased-array transducer. AB - A dual-curvature focused ultrasound phased-array transducer with a symmetric control has been developed for noninvasive ablative treatment of tumors. The 1.5 D array was constructed in-house and the electro-acoustic conversion efficiency was measured to be approximately 65%. In vitro experiments demonstrated that the array uses 256 independent elements to achieve 2-D wide-range high-intensity electronic focusing. PMID- 22293746 TI - Modeling of composite piezoelectric structures with the finite volume method. AB - Piezoelectric devices, such as piezoelectric traveling- wave rotary ultrasonic motors, have composite piezoelectric structures. A composite piezoelectric structure consists of a combination of two or more bonded materials, at least one of which is a piezoelectric transducer. Piezoelectric structures have mainly been numerically modeled using the finite element method. An alternative approach based on the finite volume method offers the following advantages: 1) the ordinary differential equations resulting from the discretization process can be interpreted directly as corresponding circuits; and 2) phenomena occurring at boundaries can be treated exactly. This paper presents a method for implementing the boundary conditions between the bonded materials in composite piezoelectric structures modeled with the finite volume method. The paper concludes with a modeling example of a unimorph structure. PMID- 22293747 TI - Preparation and characterization of P(VDF-TrFE)/Al2O3 nanocomposite. AB - Hybrid nanocomposites based on crystalline nanoparticles dispersed in polymer matrix have been widely studied in the past few years because of the ability of these materials to combine the properties of organic polymer and inorganic nanoparticles. The aim of this work is to tune the mechanical properties of a piezoelectric polymer by adding nanoparticles to the matrix. In this paper, alumina nanoparticles were dispersed in the copolymer P(VDF-TrFE), which exhibits high piezoelectric coefficient after polarization under high electric field without needing stretching during the polarization process. Transmission electron microscopy and scanning electron microscopy demonstrate the high rate of welldispersed nanoparticles with 10% of alumina nanoparticles added to the matrix. Piezoelectric measurements indicate that P(VDF-TrFE) may be filled by up to 10 wt% of alumina while retaining its high piezoelectric properties and increasing its elastic constant by more than 20%, measured by Brillouin spectroscopy. This work opens a wide range of applications using nanoparticles with nonlinear optical, pyroelectric, magnetic, or ferroelectric properties. PMID- 22293748 TI - Improving thermal ablation delineation with electrode vibration elastography using a bidirectional wave propagation assumption. AB - Thermal ablation procedures are commonly used to treat hepatic cancers and accurate ablation representation on shear wave velocity images is crucial to ensure complete treatment of the malignant target. Electrode vibration elastography is a shear wave imaging technique recently developed to monitor thermal ablation extent during treatment procedures. Previous work has shown good lateral boundary delineation of ablated volumes, but axial delineation was more ambiguous, which may have resulted from the assumption of lateral shear wave propagation. In this work, we assume both lateral and axial wave propagation and compare wave velocity images to those assuming only lateral shear wave propagation in finite element simulations, tissue-mimicking phantoms, and bovine liver tissue. Our results show that assuming bidirectional wave propagation minimizes artifacts above and below ablated volumes, yielding a more accurate representation of the ablated region on shear wave velocity images. Area overestimation was reduced from 13.4% to 3.6% in a stiff-inclusion tissue mimicking phantom and from 9.1% to 0.8% in a radio-frequency ablation in bovine liver tissue. More accurate ablation representation during ablation procedures increases the likelihood of complete treatment of the malignant target, decreasing tumor recurrence. PMID- 22293749 TI - Pulse wave imaging of the human carotid artery: an in vivo feasibility study. AB - Noninvasive quantification of regional arterial stiffness, such as measurement of the pulse wave velocity (PWV), has been shown to be of high clinical importance. Pulse wave imaging (PWI) has been previously developed by our group to visualize the propagation of the pulse wave along the aorta and to estimate the regional PWV. The objective of this paper is to determine the feasibility of PWI in the human carotid artery in vivo. The left common carotid arteries of eight (n = 8) healthy volunteers (male, age 27 + 4 years old) were scanned in a long-axis view, with a 10-MHz linear-array transducer. The beam density of the scan was reduced to 16 beams within an imaging width of 38 mm. The frame rate of ultrasound imaging was therefore increased to 1127 Hz at an image depth of 25 mm. The RF ultrasound signals were then acquired at a sampling rate of 40 MHz and used to estimate the velocity of the arterial wall using a 1-D cross-correlationbased speckle tracking method. The sequence of the wall velocity images at different times depicts the propagation of the pulse wave in the carotid artery from the proximal to distal sides. The regional PWV was estimated from the spatiotemporal variation of the wall velocities and ranged from 4.0 to 5.2 m/s in eight (n = 8) normal subjects, in agreement with findings reported in the literature. PWI was thus proven feasible in the human carotid artery, and may be proven useful for detecting vascular disease through mapping the pulse wave and estimating the regional PWV in the carotid artery. PMID- 22293750 TI - Design and implementation of a smartphone-based portable ultrasound pulsed-wave Doppler device for blood flow measurement. AB - Blood flow measurement using Doppler ultrasound has become a useful tool for diagnosing cardiovascular diseases and as a physiological monitor. Recently, pocket-sized ultrasound scanners have been introduced for portable diagnosis. The present paper reports the implementation of a portable ultrasound pulsed-wave (PW) Doppler flowmeter using a smartphone. A 10-MHz ultrasonic surface transducer was designed for the dynamic monitoring of blood flow velocity. The directional baseband Doppler shift signals were obtained using a portable analog circuit system. After hardware processing, the Doppler signals were fed directly to a smartphone for Doppler spectrogram analysis and display in real time. To the best of our knowledge, this is the first report of the use of this system for medical ultrasound Doppler signal processing. A Couette flow phantom, consisting of two parallel disks with a 2-mm gap, was used to evaluate and calibrate the device. Doppler spectrograms of porcine blood flow were measured using this stand-alone portable device under the pulsatile condition. Subsequently, in vivo portable system verification was performed by measuring the arterial blood flow of a rat and comparing the results with the measurement from a commercial ultrasound duplex scanner. All of the results demonstrated the potential for using a smartphone as a novel embedded system for portable medical ultrasound applications. PMID- 22293751 TI - APRIN is a cell cycle specific BRCA2-interacting protein required for genome integrity and a predictor of outcome after chemotherapy in breast cancer. AB - Mutations in BRCA2 confer an increased risk of cancer development, at least in part because the BRCA2 protein is required for the maintenance of genomic integrity. Here, we use proteomic profiling to identify APRIN (PDS5B), a cohesion associated protein, as a BRCA2-associated protein. After exposure of cells to hydroxyurea or aphidicolin, APRIN and other cohesin components associate with BRCA2 in early S-phase. We demonstrate that APRIN expression is required for the normal response to DNA-damaging agents, the nuclear localisation of RAD51 and BRCA2 and efficient homologous recombination. The clinical significance of these findings is indicated by the observation that the BRCA2/APRIN interaction is compromised by BRCA2 missense variants of previously unknown significance and that APRIN expression levels are associated with histological grade in breast cancer and the outcome of breast cancer patients treated with DNA-damaging chemotherapy. PMID- 22293752 TI - DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients. AB - In addition to genetic predisposition, environmental and lifestyle factors contribute to the pathogenesis of type 2 diabetes (T2D). Epigenetic changes may provide the link for translating environmental exposures into pathological mechanisms. In this study, we performed the first comprehensive DNA methylation profiling in pancreatic islets from T2D and non-diabetic donors. We uncovered 276 CpG loci affiliated to promoters of 254 genes displaying significant differential DNA methylation in diabetic islets. These methylation changes were not present in blood cells from T2D individuals nor were they experimentally induced in non diabetic islets by exposure to high glucose. For a subgroup of the differentially methylated genes, concordant transcriptional changes were present. Functional annotation of the aberrantly methylated genes and RNAi experiments highlighted pathways implicated in beta-cell survival and function; some are implicated in cellular dysfunction while others facilitate adaptation to stressors. Together, our findings offer new insights into the intricate mechanisms of T2D pathogenesis, underscore the important involvement of epigenetic dysregulation in diabetic islets and may advance our understanding of T2D aetiology. PMID- 22293754 TI - Modulation of glucose metabolism by CD44 contributes to antioxidant status and drug resistance in cancer cells. AB - An increased glycolytic flux accompanied by activation of the pentose phosphate pathway (PPP) is implicated in chemoresistance of cancer cells. In this study, we found that CD44, a cell surface marker for cancer stem cells, interacts with pyruvate kinase M2 (PKM2) and thereby enhances the glycolytic phenotype of cancer cells that are either deficient in p53 or exposed to hypoxia. CD44 ablation by RNA interference increased metabolic flux to mitochondrial respiration and concomitantly inhibited entry into glycolysis and the PPP. Such metabolic changes induced by CD44 ablation resulted in marked depletion of cellular reduced glutathione (GSH) and increased the intracellular level of reactive oxygen species in glycolytic cancer cells. Furthermore, CD44 ablation enhanced the effect of chemotherapeutic drugs in p53-deficient or hypoxic cancer cells. Taken together, our findings suggest that metabolic modulation by CD44 is a potential therapeutic target for glycolytic cancer cells that manifest drug resistance. PMID- 22293757 TI - Osteoarthritis: The hedgehog and the bony spur. PMID- 22293756 TI - HMGB1: a multifunctional alarmin driving autoimmune and inflammatory disease. AB - HMGB1 is a non-histone nuclear protein that can serve as an alarmin to drive the pathogenesis of inflammatory and autoimmune disease. Although primarily located in the cell nucleus, HMGB1 can translocate to the cytoplasm, as well as the extracellular space, during cell activation and cell death; during activation, HMGB1 can undergo post-translational modifications. The activity of HMGB1 varies with the redox states of the cysteine residues, which are required for binding to TLR4. In addition to stimulating cells directly, HMGB1 can form immunostimulatory complexes with cytokines and other endogenous and exogenous factors. In the synovia of patients with rheumatoid arthritis, as well as animal models of this disease, extranuclear expression of HMGB1 is increased and blockade of HMGB1 expression attenuates disease in animal models. In systemic lupus erythematosus, HMGB1 can be a component of immune complexes containing anti-DNA because of its interaction with DNA. In myositis, expression of HMGB1 is enhanced in inflamed muscle and can perturb muscle function. Together, these findings indicate that HMGB1 might be an important mediator and biomarker in rheumatic diseases as well as a target of new therapy. PMID- 22293759 TI - Fracture healing under healthy and inflammatory conditions. AB - Optimal fracture treatment requires knowledge of the complex physiological process of bone healing. The course of bone healing is mainly influenced by fracture fixation stability (biomechanics) and the blood supply to the healing site (revascularization after trauma). The repair process proceeds via a characteristic sequence of events, described as the inflammatory, repair and remodeling phases. An inflammatory reaction involving immune cells and molecular factors is activated immediately in response to tissue damage and is thought to initiate the repair cascade. Immune cells also have a major role in the repair phase, exhibiting important crosstalk with bone cells. After bony bridging of the fragments, a slow remodeling process eventually leads to the reconstitution of the original bone structure. Systemic inflammation, as observed in patients with rheumatoid arthritis, diabetes mellitus, multiple trauma or sepsis, can increase fracture healing time and the rate of complications, including non-unions. In addition, evidence suggests that insufficient biomechanical conditions within the fracture zone can influence early local inflammation and impair bone healing. In this Review, we discuss the main factors that influence fracture healing, with particular emphasis on the role of inflammation. PMID- 22293762 TI - Hypoxia--a key regulator of angiogenesis and inflammation in rheumatoid arthritis. AB - The importance of inflammation in rheumatoid arthritis (RA) is well understood. This knowledge has resulted in the development of anti-inflammatory therapies- either broadly acting (such as steroids) or more specific approaches (such as antibodies against TNF)--with biologic therapies (including TNF inhibitors) revolutionizing the treatment of RA. However, what is less well appreciated in RA are the links between inflammation, blood-vessel formation (angiogenesis) and cellular responses to changes in oxygen tension. Inadequate oxygenation, termed hypoxia, is thought to drive the increase in synovial angiogenesis that occurs in RA, through expression of hypoxia-inducible molecules, including vascular endothelial growth factor (VEGF). This process promotes further infiltration of inflammatory cells and production of inflammatory mediators, perpetuating synovitis. This Review highlights the molecular pathways activated by hypoxia, and how these pathways might interact with inflammatory signaling to promote and maintain synovitis in RA, with a particular focus on the response of macrophages to hypoxia in the context of RA. Successful treatment of RA, for example with anti-TNF antibodies, reduces levels of proangiogenic factors, including VEGF, and leads to normalization of the vasculature. These processes emphasise the close links between hypoxia, angiogenesis and inflammation in this disease and supports the concept that angiogenesis blockade could be of therapeutic benefit in RA. PMID- 22293764 TI - Triggers of acute cardiovascular events and potential preventive strategies: prophylactic role of regular exercise. AB - There is now considerable evidence to suggest that acute myocardial infarction, sudden cardiac death, and stroke can be triggered by physical, chemical, and psychological stressors, including heavy physical exertion and situations that create heightened emotional stress. The increased risk appears to be largely limited to a susceptible subset of the population, that is, individuals with known or occult cardiovascular (CV) disease. In this article, we summarize the evidence supporting the impact of selected triggers in the pathogenesis of acute CV events, as well as the potential role of various preventive strategies, especially regular exercise training and improvements in cardiorespiratory fitness to reduce the CV risk imposed by various triggers. PMID- 22293763 TI - The influence of ACPA status and characteristics on the course of RA. AB - Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, and affects 0.5-1% of the population. Although it poses a considerable health problem, relatively little remains known about the disease pathogenesis and etiology. In the past decade, anti-citrullinated protein antibodies (ACPA) have emerged as suspects in the development and/or progression of RA. Citrullinated proteins--containing the amino acid citrulline, generated post-translationally from arginine--are found in the joints of patients with RA, but are not specific for the disease. This situation contrasts with the presence of ACPA, which are mostly found in individuals with RA. Intriguingly, ACPA can also be found in individuals before symptom onset. In these instances the ACPA response seems to be in its infancy, recognizing only a few citrullinated antigens and not using the full isotype repertoire. These characteristics of the ACPA response mature before clinical disease precipitates. Evidence is emerging that ACPA status can further characterize the heterogeneous RA phenotype, not only with respect to outcome, but perhaps also with respect to intervention. This Review summarizes the evolution of the ACPA response and its putative role in disease pathogenesis, as well as its relationship with clinical phenotype and diagnostic potential. PMID- 22293765 TI - Overview of sudden cardiac death in young athletes. AB - Sudden cardiac death is the leading cause of nontraumatic mortality in young athletes. The estimated incidence varies; however, recent studies have provided more accurate data. Most cases are attributed to silent hereditary or congenital cardiac disorders, many of which may be detected through preparticipation screening programs. This article provides a comprehensive review of the incidence and etiology of sudden cardiac death in young athletes, with practical advice regarding evaluation and management in light of a large number of recent advances. A brief outline of current perspectives on preparticipation screening programs and prevention is included. PMID- 22293766 TI - Exercise as a nonpharmacologic intervention in patients with heart failure. AB - For patients with heart failure (HF), dyspnea and fatigue resulting in diminished exercise tolerance are among the main factors that contribute to decreased social and physical functioning and quality of life. There has long been evidence to suggest that measures of cardiac function, such as ejection fraction and cardiac output, only poorly correlate with a patient's exercise capacity, indicating the involvement of factors other than those impacting central circulation. The lack of a close correlation between central hemodynamics and exercise tolerance has led to investigations into alterations in the periphery, such as abnormalities in vascular endothelial function, hyperactivation of the sympathetic nervous system, and changes in structure and oxidative capacity of skeletal muscle, which are commonly seen in patients with HF. Over the past 2 decades, numerous clinical trials have demonstrated the beneficial impact of exercise training on skeletal muscle energy metabolism, vascular function, and ventilatory capacity, which correlate with improvements in exercise tolerance, hospitalization rates, and quality of life of patients with HF. In accordance with recent guidelines established by the leading cardiology societies in the United States and Europe, physicians are urged to emphasize exercise training for all clinically stable patients with HF using individualized protocols that feature early mobilization after acute exacerbations of the disease and gradual increases in intensity. PMID- 22293767 TI - Is quadriceps muscle weakness a risk factor for incident or progressive knee osteoarthritis? AB - The role of the quadriceps muscle in mediating risk for knee osteoarthritis (OA) is a common subject of investigation. The quadriceps muscle is a principal contributor to knee joint stability and provides shock absorption for the knee during ambulation. Clinically, weakness of the quadriceps muscle is consistently found in patients with knee OA. Research has shown that higher quadriceps muscle strength is associated with a reduced risk for incident symptomatic knee OA. However, there is limited evidence to suggest that quadriceps muscle plays a significant role in the incidence of radiographic knee OA. In addition, greater quadriceps muscle strength is associated with a lower risk for progression of tibiofemoral joint space narrowing and cartilage loss in women. This article summarizes knowledge of the relationship between quadriceps muscle strength and risk for knee OA. PMID- 22293768 TI - Participation in athletic activities may be associated with later development of hip and knee osteoarthritis. AB - Participation in physical activity and recreational sports is critical for maintaining overall health; athletic activities and reduction in the incidence of several "lifestyle" diseases seem to have a dose-dependent relationship. Also, quality of life is enhanced in people who are active and regularly participate in sports. However, sports-related joint loading and strenuous occupational loading have been shown to increase the risk of osteoarthritis (OA), which seems to have a multifactorial etiology. This article reviews the literature on known connections between participation in sports and athletic activities and development of secondary OA in the joints of the major upper and lower limbs (ie, knee, hip, elbow, and shoulder) in athletes without injury. Most studies examining the connection between participation in sports and later development of OA usually provide low-level evidence and have many methodological weaknesses. Based on the literature reviewed in this article, it may be concluded that the connection between participation in athletic activities and development of OA has not been proven; however, the condition is highly likely to occur in the hip and knee joints. Definite conclusions regarding the connection between development of glenohumeral and/or elbow OA and participation in athletic activities cannot be drawn. PMID- 22293769 TI - Evaluation and management of osteochondral lesions of the knee. AB - Osteochondral lesions of the knee is a common disorder in adolescents, although it may present in children and adults. Despite the fact that the disorder was discovered more than a century ago, no specific causes have been identified, although relationships with ischemia, irregular ossification of epiphyseal cartilage, genetic influences, trauma, and endocrine disorders have been postulated. Taking a thorough history and performing a thorough physical examination will facilitate diagnosis of this condition. Radiographic and magnetic resonance imaging are useful diagnostic tools that aid in the evaluation. A comprehensive knowledge of the relevant anatomy and clinical progression of osteochondral lesions allows for a better understanding of the classification systems and, ultimately management of this disorder. The size, location, and stability of the lesion, as well as the patient's age, are crucial in determining optimal treatment. The spectrum of injury ranges from small, stable lesions, which can be treated nonoperatively, to unstable or displaced lesions, which may require surgical management. Surgical options include drilling of subchondral bone, curettage and microfracture, refixation of detached lesions, autologous osteochondral autograft procedures (eg, mosaicplasty, osteochondral autograft transfer system), autologous chondrocyte implantation, and osteochondral allograft resurfacing. This article provides a basic approach to the evaluation and management of osteochondral lesions, as well as indications for surgery. PMID- 22293770 TI - A public health perspective on physical activity after total hip or knee arthroplasty for osteoarthritis. AB - Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are common treatments for osteoarthritis (OA) with good-to-excellent outcomes. As the US population ages, rates of OA and THA/TKA will continue to rise. People with OA and THA/TKA are less active than those without arthritis or arthrosplasty, respectively. With the numerous documented health benefits obtained from physical activity, it is imperative from a public health perspective that patients are sufficiently active to maintain health after surgery. Increasing moderate intensity physical activity is a safe, efficacious, and cost-effective mechanism for improving health and reducing health care costs in this population. The return to leisure/sporting activities after THA/TKA is not as well studied as other aspects of functional recovery. In particular, no evidence-based guidelines for physical activity after THA/TKA are available. Most recommendations have been derived from cross-sectional surveys of orthopedic surgeons. Based on the literature, the general consensus for recommendations appears to be to: 1) return to low- to moderate-intensity activities and no-, low-, or intermediate-impact activities within 3 to 6 months postoperatively, 2) discourage high-impact activities, 3) avoid high-contact athletic activities, and 4) educate rather than dissuade patients from resuming leisure/sporting activities. Sports medicine physicians are in an ideal position to counsel patients in regard to leading active lifestyles. The physician can evaluate and treat any remaining functional limitations postoperatively, as well as prescribe the appropriate dose (ie, type, intensity, frequency, and duration) of physical activity. The 2008 Physical Activity Guidelines for Americans can help guide physicians in prescribing the appropriate dose of activity. Finally, physicians can refer patients to evidence based, community-delivered group exercise and/or behavioral change interventions that are approved by the Centers for Disease Control and Prevention for people with arthritis. PMID- 22293771 TI - Back pain in adolescent athletes. AB - Back pain in the young athlete is a common complaint and often perceived as a challenging problem. A well-directed approach will usually provide the practitioner with a higher comfort zone. The etiology of back pain in the pediatric and adolescent population is different from that of the adult population due to the presence of open physes and increased linear growth velocity. In addition, the frequency and intensity of sports participation in children continues to increase, leading to more overuse injuries. This review article will discuss the anatomy and physiology of the spine and pelvis, as well as focus on the chronic and overuse causes of back pain in the young athlete. PMID- 22293772 TI - The Advanced Throwers Ten Exercise Program: a new exercise series for enhanced dynamic shoulder control in the overhead throwing athlete. AB - The overhead throwing motion is a high-velocity, extremely stressful athletic movement. Its repetitive nature places tremendous demands on the entire body, frequently resulting in injury to the throwing shoulder. Such injuries, whether managed nonoperatively or surgically, require a multiphased approach beginning with exercises to restore muscular strength and proprioception, and advancing to more demanding exercises to improve power, endurance, and dynamic control. This article presents a new and innovative approach to the rehabilitation of the overhead throwing athlete, The Advanced Throwers Ten Exercise Program. This expanded program incorporates throwing motion-specific exercises and movement patterns performed in a discrete series, utilizing principles of coactivation, high-level neuromuscular control, dynamic stabilization, muscular facilitation, strength, endurance, and coordination, which all serve to restore muscle balance and symmetry in the overhead throwing athlete. This program is a continuation of the Throwers Ten Exercise Program, which has been utilized with excellent results in clinical practice and in athletic performance training. This unique combination of advanced exercise techniques bridges the gap between rehabilitation and training, facilitating a kinetic linking of the upper and lower extremities and providing a higher level of humeral head control necessary for the overhead throwing athlete's symptom-free return to sports. PMID- 22293773 TI - 2011 recommendations for the diagnosis and management of gout and hyperuricemia. AB - Gout is a major health problem in the United States; it affects 8.3 million people, which is approximately 4% of the adult population. Gout is most often diagnosed and managed in primary care practices; thus, primary care physicians have a significant opportunity to improve patient outcomes. Following publication of the 2006 European League Against Rheumatism (EULAR) gout guidelines, significant new evidence has accumulated, and new treatments for patients with gout have become available. It is the objective of these 2011 recommendations to update the 2006 EULAR guidelines, paying special attention to the needs of primary care physicians. The revised 2011 recommendations are based on the Grading of Recommendations Assessment, Development, and Evaluation approach as an evidence-based strategy for rating quality of evidence and grading the strength of recommendation formulated for use in clinical practice. A total of 26 key recommendations, 10 for diagnosis and 16 for management, of patients with gout were evaluated, resulting in important updates for patient care. The presence of monosodium urate crystals and/or tophus and response to colchicine have the highest clinical diagnostic value. The key aspect of effective management of an acute gout attack is initiation of treatment within hours of symptom onset. Low dose colchicine is better tolerated and is as effective as a high dose. When urate-lowering therapy (ULT) is indicated, the xanthine oxidase inhibitors allopurinol and febuxostat are the options of choice. Febuxostat can be prescribed at unchanged doses for patients with mild-to-moderate renal or hepatic impairment. The target of ULT should be a serum uric acid level that is <= 6 mg/dL. For patients with refractory and tophaceous gout, intravenous pegloticase is a new treatment option. This article is a summary of the 2011 clinical guidelines published in Postgraduate Medicine. This article provides a streamlined, accessible overview intended for quick review by primary care physicians, with the full guidelines being a resource for those seeking additional background information and expanded discussion. PMID- 22293774 TI - Eminence-based medicine versus evidence-based medicine: level V evidence in sports medicine. AB - Through extensive survey analysis, we investigated expert opinion in sports medicine. The study had 3 purposes: to provide clinical guidance for cases in which the correct action is not necessarily apparent, to examine expert opinion itself, and to delineate areas of future study. A total of 500 members of the American Medical Society for Sports Medicine and the American Orthopaedic Society for Sports Medicine evaluated a set of 25 statements on unresolved issues in sports medicine. The following 10 statements were deemed false: "It's okay for 12 year-old pitchers to throw curve balls; it's the pitch count that matters"; "Resistance training ('weight lifting') should be avoided until physeal closure"; "Jogging during pregnancy is to be avoided"; "At an athletic event, if sideline coverage is offered by an emergency medical technician and athletic trainer, there is little additional benefit from having a physician present"; "Contact sport athletes who sustain a second concussion should be excluded from contact sports permanently"; "The utility of pre-season medical screening is derived from the history; as such, student-athletes should complete a questionnaire, with physical examination reserved for only those with a positive relevant history"; "Femoroacetabular impingement is a myth-the designation of anatomic variation as disease"; "An AC (acromioclavicular) separation in a contact athlete should not be treated surgically if the athlete won't give up the sport; it will fail"; "Ankle taping induces weakness and atrophy of the dynamic stabilizers of the ankle"; "Only autografts should be used in ACL (anterior cruciate ligament) surgery, as allografts have an unnecessary high failure rate in clinical practice." One statement was accepted as true: "Surgery to treat anterior (patello-femoral) knee pain in a patient with normal patellar mechanics and stability is contraindicated." In short, expert opinion may be a helpful adjunct to clinical practice. Expert opinion cannot replace individual judgment and certainly does not trump the primary medical literature. Yet when better evidence is lacking, expert opinion is valuable for even the staunchest practitioner of evidence-based medicine. PMID- 22293775 TI - gamma-Tocotrienol attenuates TNF-alpha-induced changes in secretion and gene expression of MCP-1, IL-6 and adiponectin in 3T3-L1 adipocytes. AB - Tocotrienols, members of the vitamin E family, have been shown to possess anti inflammatory properties and display activity against a variety of chronic diseases, such as cancer, cardiovascular and neurological diseases. However, whether tocotrienols contribute to the prevention of inflammatory responses in adipose tissue remains to be elucidated. In this study, we examined the effects of gamma-tocotrienol, the most common tocotrienol isomer, on tumor necrosis factor-alpha (TNF-alpha)-induced inflammatory responses by measuring the expression of the adipokines, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and adiponectin in 3T3-L1 adipocytes. Exposure to TNF-alpha (10 ng/ml) for 24 h increased MCP-1 and IL-6 secretion, and decreased adiponectin secretion and peroxisome proliferator-activated receptor-gamma (PPARgamma) mRNA expression. gamma-tocotrienol effectively improved the TNF-alpha-induced adverse changes in MCP-1, IL-6 and adiponectin secretion, and in MCP-1, IL-6, adiponectin and PPARgamma mRNA expression. Furthermore, TNF-alpha-mediated IkappaB-alpha phosphorylation and nuclear factor-kappaB (NF-kappaB) activation were significantly suppressed by the gamma-tocotrienol treatment. Our results suggest that gamma-tocotrienol may improve obesity-related functional abnormalities in adipocytes by attenuating NF-kappaB activation and the expression of inflammatory adipokines. PMID- 22293776 TI - Photoconductive and supramolecularly engineered organic field-effect transistors based on fibres from donor-acceptor dyads. AB - We report on the formation of photoconductive self-assembled fibres by solvent induced precipitation of a HBC-PMI donor-acceptor dyad. Kelvin Probe Force Microscopy revealed that upon illumination with white light the surface potential of the fibres shifted to negative values due to a build-up of negative charge. When integrated in a field-effect transistor (FET) configuration, the devices can be turned 'on' much more efficiently using light than conventional bias triggered field-effect, suggesting that these structures could be used for the fabrication of light sensing devices. Such a double gating represents an important step towards bi-functional organic FETs, in which the current through the junction can be modulated both optically (by photoexcitation) and electrically (by gate control). PMID- 22293777 TI - Selective decontamination in European intensive care patients. PMID- 22293778 TI - Preventive effect of caffeine and curcumin on hepato-carcinogenesis in diethylnitrosamine-induced rats. AB - Chemopreventive effects of caffeine and curcumin were evaluated in the diethylnitrosamine (DEN)-induced hepatocarcinogenic rat model. Animals injected with DEN for 10 weeks (G2-10w) and 14 weeks (G2-14w) were hepato-carcinogenic rats. Animals injected with DEN and treated with curcumin and caffeine for 10 weeks (G3-10w, G4-10w) and 14 weeks (G3-14w, G4-14w) were compared with those in G2. Macroscopic and microscopic features suggested that treatment with caffeine, but not curcumin, for 10 and 14 weeks was effective in inhibiting DEN-induced hepatocarcinogenesis. Immunohistochemical and western blot analysis with proliferating cell nuclear antigen and glutathione S-transferase-P antibodies also showed that expression levels of these hepato-carcinogenic markers were more efficiently reduced by treatment with caffeine than curcumin. Our data demonstrate that caffeine could be a more potent compound than curcumin for prevention of hepatocarcinogenesis in DEN-induced rats. PMID- 22293779 TI - Increase in cardiac M2-muscarinic receptor expression is regulated by GATA binding protein 4 (GATA-4) in streptozotocin-induced diabetic rats. AB - BACKGROUND: An increase in cardiac M2-muscarinic receptor (M2-mAChR) expression in diabetic rats has been observed, but the molecular mechanism of this increase remains unclear. The transcriptional activity of GATA binding protein 4 (GATA-4) has been documented to regulate the expression of M2-mAChR genes. In this study, we were interested in identifying the role of GATA-4 in the increase in M2-mAChR in diabetic rats and a primary culture of cardiomyocytes. METHODS: Streptozotocin induced diabetic rats (STZ-rats) and high-glucose (D-glucose 30 mM, 24h)-treated primary cultures of cardiomyocytes from neonatal rats were used to investigate the role of GATA-4 in the change in M2-mAChR. The protein expression was determined by Western blot analysis. Phlorizin (Na(+)-glucose co-transport inhibitor), insulin, tiron (radical scavenger), PD98059 (ERK inhibitor) and SB203580 (p38 inhibitor) were used. We also silenced GATA-4 by RNAi to investigate the changes in M2-mAChR expression. RESULTS: The cardiac output was reduced in STZ-rats with a higher expression of M2-mAChR or phosphorylated GATA-4 in the heart. These changes were reversed after correction of the blood sugar level. In cardiomyocytes, high glucose treatment also increased M2-mAChR expression and GATA-4 phosphorylation. These changes were reversed by tiron (ROS scavenger) or PD98059 (MEK/ERK inhibitor). However, an increase in M2-mAChR expression was not observed when GATA-4 was silenced by small interfering RNA (siRNA) in cardiomyocytes. CONCLUSIONS: We suggest that hyperglycemia can cause a higher expression of M2-mAChR in cardiomyocytes mainly through ROS to enhance MEK/ERK for phosphorylation of GATA-4. PMID- 22293780 TI - The incidence of C5 palsy after multilevel cervical decompression procedures: a review of 750 consecutive cases. AB - STUDY DESIGN: Retrospective review of 750 consecutive multilevel cervical spine decompression surgeries performed by a single spine surgeon. OBJECTIVE: To determine the incidence of C5 palsy in a large consecutive series of multilevel cervical spine decompression procedures. SUMMARY OF BACKGROUND DATA: Palsy of the C5 nerve is a well-known potential complication of cervical spine surgery with reported rates ranging from 0% to 30%. The etiology remains uncertain but has been attributed to iatrogenic injury during surgery, tethering from shifting of the spinal cord, spinal cord ischemia, and reperfusion injury of the spinal cord. METHODS: We included patients undergoing multilevel cervical corpectomy, corpectomy with posterior fusion, posterior laminectomy and fusion, and laminoplasty. Exclusion criteria included lack of follow-up data, spinal cord injury preventing preoperative or postoperative motor testing, or surgery not involving the C5 level. Incidence of C5 palsy was determined and compared to determine whether significant differences existed among the various procedures, patient age, sex, revision surgery, preoperative weakness, diabetes, smoking, number of levels decompressed, and history of previous upper extremity surgery. RESULTS: Of the 750 patients, 120 were eliminated on the basis of the exclusion criteria. The 630 patients included in the analysis consisted of 292 females and 338 males. The mean age was 58 years (range, 19-87). The incidence of C5 nerve palsy for the entire group was 42 of 630 (6.7%). The incidence was highest for the laminectomy and fusion group (9.5%), followed by the corpectomy with posterior fusion group (8.4%), the corpectomy group (5.1%), and finally the laminoplasty group (4.8%), although these differences did not reach statistical significance. There was a significantly higher incidence in males (8.6% vs. 4.5%, P = 0.05). CONCLUSION: Incidence of C5 nerve palsy after cervical spine decompression was 6.7%. This is consistent with previously published studies and represents the largest series of North American patients to date. There is no statistically significant difference in incidence of C5 palsy based on surgical procedure, although there was a trend toward higher rates with laminectomy and fusion. PMID- 22293781 TI - Adenovirus-mediated delivery of CALR and MAGE-A3 inhibits invasion and angiogenesis of glioblastoma cell line U87. AB - BACKGROUND: The management of patients with glioblastoma multiforme is difficult. Poor results have led to a search for novel therapeutic approaches. Gene therapy that could be both anti-invasive and antiangiogenic would be ideal. In this study, we constructed the recombinant adenoviral vector Ad-CALR/MAGE-A3 and evaluated its antitumor effects on glioblastoma in vitro and in vivo. METHODS: In this study, CALR and MAGE-A3 genes were delivered to the glioblastoma cell line U87, using adenovirus (Ad-CALR/MAGE-A3). U87 glioblastoma cells were transfected with Ad-green fluorescent protein to identify the multiplicity of infection. The expressions of CALR and MAGE-A3 were detected by PCR and Western blot. Cell proliferation was measured by MTT assay. Cell apoptosis was assessed by Annexin-V FITC/PI double staining flow cytometry. The invasive potential of U87 cells was determined by Matrigel invasion assay. Tube formation assay was used to detect the effects on angiogenesis of human umbilical vein endothelial cells. Protein expressions of PI3K/AKT, Erk1/2 and MMP-2/-9 in transfected cells were detected by Western blot. In vivo, the effects of Ad-CALR/MAGE-A3 on tumor growth and angiogenesis of U87 glioblastoma xenografts in nude mice were investigated. RESULTS: The expressions of CALR and MAGE-A3 in U87 cells resulted in the suppression of cell proliferation and invasion properties, and induced cell apoptosis. The Erk MAPK, PI3K/AKT pathways and expressions of MMP-2/-9 were inhibited in Ad-CALR/MAGE-A3-transfected cells. Outcomes of the tube formation assay confirmed the antiangiogenic effect of CALR. Moreover, in the in vivo model of glioblastoma, intratumoral injection of Ad-CALR/MAGE-A3 suppressed tumor growth and angiogenesis. CONCLUSION: Although Ad-CALR/MAGE-A3 and Ad-CALR demonstrated antiangiogenic effects on U87 cells, the repression of invasion was significant only in Ad-CALR/MAGE-A3-treated cells. To our knowledge, this is the first description of a role for combined CALR and MAGE-A3 in the anti-invasion and antiangiogenesis of U87. PMID- 22293782 TI - No association between infections, HLA type and other transplant-related factors and risk of cutaneous squamous cell carcinoma in solid organ transplant recipients. AB - Recipients of solid organ transplants are at a markedly increased risk of cutaneous squamous cell carcinoma (SCC). We investigated potential associations between post-transplant infections, HLA type, and other transplant-related factors and risk of SCC, taking immuno-suppressive treatment into account. A population-based case-control study was conducted. All patients who developed SCC during follow-up (1970-1997) were eligible as cases (n = 207). Controls (n = 189) were individually matched to the cases on age and calendar period of transplantation. Detailed exposure information was collected through an extensive, blinded review of medical records. Odds ratios were computed with conditional logistic regression. There were no significant associations with any infectious agents, or with number and timing of infections, specific HLA-type, donor characteristics, or other transplant characteristics and risk of post transplant SCC. These results suggest that risk of post-transplant SCC is neither closely related to specific post-transplant infectious disorders, nor to the infectious load or specific HLA types. PMID- 22293784 TI - [Gastrointestinal tumors]. PMID- 22293786 TI - [Tumors of Vater's ampulla]. AB - Tumors of Vater's ampulla are generally uncommon. In this location intestinal type adenomas are frequently found, followed by noninvasive papillary neoplasms of the pancreaticobiliary type and neuroendocrine tumors (carcinoids). Carcinomas of Vater's ampulla represent about 0.5% of all gastrointestinal malignancies. Intestinal type adenocarcinoma is the most common malignant epithelial tumor followed by the pancreaticobiliary type adenocarcinoma. Highly malignant neuroendocrine carcinomas of Vater's ampulla are very uncommon. Carcinomas of the ampullary region can be sporadic or a component of several disease syndromes. Designation of large carcinomas as tumors with an ampullary or extra-ampullary origin can be difficult but is of relevance for a TNM conform classification. Helpful in the decision are the relationship between the tumor centre and Vater's ampulla, the existence of premalignant lesions in the ampullary epithelium as well as histology and immunostaining of the tumor. PMID- 22293785 TI - [Barrett's esophagus. An update]. AB - Barrett's esophagus (BE), a well-known complication of gastroesophageal reflux disease (GERD), constitutes a precancerous condition for adenocarcinoma of the distal esophagus. The so-called Barrett's carcinoma shows increasing incidences in countries of the western hemisphere; new data, however, indicate that the rise in incidence is not quite as dramatic as previously assumed. The definition of BE is currently changing: despite good reasons for a purely endoscopic definition of BE, goblet cells are still mandatory for this diagnosis in Germany and the USA. Dysplastic changes in the epithelium are the most important risk factor for the development of Barrett's adenocarcinoma and recently dysplasia was subclassified into a more frequent adenomatous (intestinal) and a non-adenomatous (gastric foveolar) types. The gold standard for diagnosing dysplasia is still H&E staining. The histological diagnosis of dysplasia is still encumbered by a significant interobserver variability, especially regarding the differentiation between low grade dysplasia and inflammatory/reactive changes and the discrimination between high grade dysplasia and adenocarcinoma. Current data, however, show much higher interobserver agreement in endoscopic resection specimens than in biopsies. Nevertheless, the histological diagnosis of dysplasia should be corroborated by an external second opinion because of its clinical consequences. In endoscopic resections of early Barrett's adenocarcinoma, the pathological report has to include a risk stratification for the likelihood of lymphogenic metastases. PMID- 22293787 TI - [Gastrointestinal mixed adenoneuroendocrine carcinomas. An attempt at classification of mixed cancers]. AB - Mixed adenoneuroendocrine carcinomas (MANECs) are a challenge for the diagnostics and the concept of a histogenetic tumor typing. They are classified into three malignant subgroups: high grade malignant MANECs combine an adenoma or adenocarcinoma with a small cell or large cell neuroendocrine carcinoma, intermediate grade malignant MANECs consist of a neuroendocrine tumor (NET grade 1 or 2), often a globlet cell carcinoid and a poorly differentiated adenocarcinoma or diffuse carcinoma of signet ring cell type. The prototype of a low grade malignant MANEC is the globlet cell carcinoid. Molecular analysis indicates a common clonal origin of the different components in MANECs. The prognosis is determined by the most aggressive tumor component. The pathogenesis of MANECs is apparently a sequence of increasing malignant transformation which leads either from an adenoma/adenocarcinoma to a small or large cell neuroendocrine carcinoma or from a neuroendocrine tumor (NET), often a globlet cell carcinoid to a poorly differentiated adenocarcinoma or a diffuse carcinoma of signet ring cell type. PMID- 22293788 TI - [Prognostic marker profiles for risk of distant metastases in colorectal cancer]. AB - In colorectal cancer (CRC) prognostic markers correlating with distant metastasis are of high clinical value. In recent years it could be demonstrated that sporadic CRC with microsatellite instability (MSI) exhibits a very low risk for distant spread. Within this group the medullary subtype represents a morphological prototype. In the new WHO classification other morphological variants, such as mucinous, signet ring cell, serrated, cribriform comedo type and solid-undifferentiated forms are graded according to their microsatellite status. The clinical value of BRAF mutations is also dependent on the microsatellite status. Recent data have shown an ambivalent prognostic impact of BRAF mutations. A BRAF mutation in combination with MSI is associated with a good prognosis, whereas a BRAF mutation in the background of microsatellite stability (MSS) indicates a very poor outcome. Based on the concept of migrating stem cells, combined high scores of CD133 and nuclear beta-catenin expression can be additionally used as markers for a high risk of distant metastasis. Hence, an immunohistochemical algorithm can be defined by the combination of three markers (hMLH1, CD133 and beta-catenin) which allows CRC with either a very high or a very low risk of distant spread to be identified. PMID- 22293789 TI - [Secondary tumors of the gastrointestinal tract]. AB - Metastatic involvement of the gastrointestinal tract is rare and may cause considerable difficulties with respect to differential diagnosis. The gastrointestinal tract may either be affected by direct invasion, intraperitoneal dissemination or hematogenous cancer spread, the latter most often originating from malignant melanoma, breast and lung carcinomas. Metastatic deposits primarily develop within the submucosa. Secondary involvement of the mucosa typically leads to centrally depressed and/or ulcerated (volcano-like) nodular lesions. In histology, lack of a mucosal in situ component favors diagnosis of metastasis, whereas presence of an adenomatous precursor lesion is regarded to be characteristic of primary tumors. This concept, however, has recently been challenged by demonstrating metastatic cancer growth along intact basement membranes within the mucosal layer, i.e. mucosal colonization. The histopathological, immunohistochemical and clinical features of secondary gastrointestinal tumors are discussed in detail, focusing on criteria for differential diagnosis. The prognosis of affected patients is generally poor. PMID- 22293790 TI - [Regression grading in gastrointestinal tumors]. AB - Preoperative neoadjuvant chemoradiation therapy is a well-established and essential part of the interdisciplinary treatment of gastrointestinal tumors. Neoadjuvant treatment leads to regressive changes in tumors. To evaluate the histological tumor response different scoring systems describing regressive changes are used and known as tumor regression grading. Tumor regression grading is usually based on the presence of residual vital tumor cells in proportion to the total tumor size. Currently, no nationally or internationally accepted grading systems exist. In general, common guidelines should be used in the pathohistological diagnostics of tumors after neoadjuvant therapy. In particularly, the standard tumor grading will be replaced by tumor regression grading. Furthermore, tumors after neoadjuvant treatment are marked with the prefix "y" in the TNM classification. PMID- 22293791 TI - [Granular cell tumor of the stomach]. AB - Granular cell tumors are peripheral neuroectodermal tumors. Within the gastrointestinal tract, they have to be differentiated from gastrointestinal stromal tumors (GIST). We present the case of a 61-year-old patient who was diagnosed with a granular cell tumor of the stomach. The tumor cells showed transmural infiltration form the mucosa into the adipose tissue of the lesser curvature. The tumor cells were diffusely positive for S100-protein and negative for KIT, CD34 und SMA. The MIB1-proliferation index was below 2%. Granular cell tumors rarely occur within the gastrointestinal tract. Oesophagus and colon are most commonly affected. Diagnostic criteria and differential diagnosis of this peculiar lesion are thoroughly discussed. PMID- 22293792 TI - [Plexiform angiomyxoid myofibroblastic tumour of the stomach]. AB - Recently the so-called plexiform angiomyxoid myofibroblastic tumors (PAMT) have emerged as a new entity of gastric soft tissue tumors and the light microscopic and immunohistological characteristics have now been well described. Until now PAMTs have not yet been reported in the German speaking literature. Worthy of note is that PAMTs can be diagnosed safely in sufficient biopsy material which enables adequate therapeutic steps to be initiated without delay, because PMATs although considered to be benign, can cause serious complications. PMID- 22293794 TI - Second-harmonic generating properties of polar noncentrosymmetric aluminoborate solid solutions, Al(5-x)Ga(x)BO9 (0.0 <= x <= 0.5). AB - A series of solid solutions of polar aluminoborate materials, Al(5-x)Ga(x)BO(9) (0.0 <=x<= 0.5) have been synthesized by standard solid-state reactions using Al(2)O(3), Ga(2)O(5), and B(OH)(3) as reagents. The phase purities, crystal structures, and solid solution behavior of the reported materials have been investigated by powder X-ray diffraction. Solid solutions of Al(5-x)Ga(x)BO(9) crystallize in the polar noncentrosymmetric space group, Cmc2(1), with a three dimensional structure consisting of distorted MO(4), MO(5), MO(6), and BO(3) polyhedra (M = Al or Ga). Powder second-harmonic generating (SHG) measurements on the Al(5)BO(9) using 1064 nm radiation, indicate the material has a SHG efficiency of approximately 2 times that of alpha-SiO(2) and is not phase matchable (type 1). Further nonlinear optical (NLO) measurements on the Al(5 x)Ga(x)BO(9) solid solutions indicate a sharp increase in SHG efficiency up to 10 times that of alpha-SiO(2) for x>= 0.4. Close structural examination suggests that the alignment of the asymmetric pi-delocalization of BO(3) groups is responsible for the abrupt increase of SHG efficiency. PMID- 22293795 TI - Electrochemical current rectifier as a highly sensitive and selective cytosensor for cancer cell detection. AB - Signal amplification originating from electrochemical current rectifier (ECR) was firstly applied to construct a cytosensor for rapid and non-invasive detection of folate receptor-rich cancer cells with high sensitivity. It exhibits a broad linear range with a detection limit as low as 10 cells mL(-1) even in the presence of a large number of normal cells. PMID- 22293796 TI - Spinal tophaceous gout. PMID- 22293797 TI - Contribution of extracardiac factors to the inconsistency between plasma B-type natriuretic peptide levels and the severity of pulmonary congestion on chest X rays in the diagnosis of heart failure. AB - OBJECTIVE: Chest X-rays and plasma B-type natriuretic peptide (BNP) levels are useful for diagnosing congestive heart failure. However, the relationship between plasma BNP levels and pulmonary congestion on chest X-rays often seems inconsistent. Extracardiac factors can directly alter plasma BNP levels, independent of cardiac function. In the present study, we examined the clinical factors that impact the diagnosis of heart failure by using chest X-rays and plasma BNP levels. METHODS AND RESULTS: This study comprised 459 consecutive patients who were admitted to the cardiovascular division of our hospital for any reason and in whom chest X-rays and plasma BNP levels were measured within 12 hours after admission. The approximate BNP value associated with pulmonary congestion that was detectable by chest X-rays was 143 pg/mL, but this value was influenced by renal function, age, and body mass index (BMI). Furthermore, we examined the effect of these three extracardiac factors on plasma BNP levels in each stage of pulmonary congestion. We found that renal dysfunction and advanced age increased the plasma BNP levels, whereas a high BMI decreased the levels, and that the effect of BMI on plasma BNP levels was greater for severe heart failure. CONCLUSION: Extracardiac factors should be considered when the relationship between the plasma BNP levels and the severity of pulmonary congestion on chest X rays seems inconsistent. In particular, low levels of plasma BNP in patients with a high BMI should be carefully considered to avoid underestimating the degree of heart failure. PMID- 22293798 TI - Increased serum bilirubin level is related to good collateral development in patients with chronic total coronary occlusion. AB - OBJECTIVE: Bilirubin is a bile pigment with potent anti-oxidant properties; in previous studies it has been reported to be negatively associated with coronary artery disease (CAD). Although elevated serum bilirubin concentrations may protect against endothelial dysfunction, it is not clear whether higher serum bilirubin levels (SBLs) in physiological ranges may work in favor of good collateral development in patients with chronic total coronary occlusion (CTO). METHODS: The study population consisted of patients who underwent coronary angiography with a suspicion of CAD. Patients who had CTO in at least one major coronary artery were included. Coronary angiograms of 179 eligible patients from our database were reanalyzed and 110 of them had good collateral development and 69 had poor collateral development according to the Cohen-Rentrop method. RESULTS: Patients with good collateral development had a lower fasting plasma glucose level (FPG) (p=0.024) and higher SBLs in comparison to patients with poor collateral development (p<0.001). The number of CTO vessels (p=0.013) and left ventricular ejection fraction (EF%) were higher in good collateral group than poor collateral group (p=0.017). In multivariate analysis, FPG negatively (odds ratio [OR]: 0.981, p=0.003) and SBL (OR for per 0.1-mg/dL increase: 1.832, p<0.001) and the number of CTO vessels (OR: 5.642, p=0.007) were positively related to coronary collateral development. CONCLUSION: This study suggests that higher bilirubin levels within relatively normal ranges were related with favorable coronary collateral growth in patients with CTO. SBL may be responsible for the difference in coronary collateral vessel development among different patients with coronary artery disease. The anti-inflammatory and anti-oxidant properties of bilirubin may mediate this effect. PMID- 22293799 TI - Direct comparison of Takotsubo cardiomyopathy between Japan and USA: 3-year follow-up study. AB - OBJECTIVE: Takotsubo cardiomyopathy (TC) mimics myocardial infarction and is well defined and known to not only Japan but also western countries. However, whether or not there are differences in the characteristics of TC between Japan and USA remains unknown. PATIENTS: Data for patients who had undergone urgent left heart catheterization for suspected acute coronary syndrome were retrospectively retrieved from Keio University School of Medicine (KUSM) database in Japan and Lahey Clinic Medical Center (LCMC) database in USA between 2002 and 2007. RESULTS: During the study period, 626 coronary angiographies were performed in KUSM and 1,880 coronary angiographies were performed in LCMC. Twelve patients in Japan and 34 patients in USA met the inclusion criteria. Mean age of patients in Japan was 75 years where 92% were women, compared to 67 years and 94% women in USA. Although the prevalence of hypertension, dyslipidemia and diabetes mellitus were similar between Japan and USA, there was a trend towards fewer patients in Japan displaying a history of coronary revascularization. Surprisingly, a family history of premature coronary artery disease (CAD) was present in 21% of USA patients, whereas no patients were present in Japan. There were no differences in the incidence of readmission for heart failure, cardiac death and TC recurrence during the follow-up period. CONCLUSION: Patients with TC in Japan have fewer prior overt CAD and fewer family history of premature CAD, but no significant differences were found in the long-term prognosis and the recurrence rate between patients in Japan and USA. PMID- 22293800 TI - The relationship between the severity of depressive symptoms and diabetes-related emotional distress in patients with type 2 diabetes. AB - OBJECTIVE: To examine the relationship between the severity of depressive symptoms and the burden through diabetes care, or diagnosed diabetes in patients with type 2 diabetes, irrespective of the diabetic complications and glycemic control. PATIENTS AND METHODS: Subjects were 126 outpatients with type 2 diabetes who completed the Beck Depression Inventory-II (BDI-II), Problem Areas in Diabetes (PAID) scale, and Short Form-36 (SF-36). RESULTS: The factor with a significant impact on the BDI-II score in the multiple regression model was the PAID score (standardized coefficient =0.17, 95% confidence interval [CI], 0.12 0.21). The factors having a significant impact on the physical component summary of SF-36 (PCS) in the multiple regression model were BDI-II score (-0.95; 95% CI, -1.32 - -0.58), age (-0.43; 95% CI, -0.61 - -0.25), and the number of complicated macroangiopathies (-8.90; 95% CI, -12.71 - -5.08). The factors with a significant impact on the mental component summary of SF-36 (MCS) in the multiple regression model were BDI-II score (-0.90; 95% CI, -1.16 - -0.65) and age (0.13; 95% CI, 0.00-0.25). CONCLUSION: These findings show that diabetes-related emotional distress is significantly related to the severity of depressive symptoms in patients with type 2 diabetes, independent of the severity of complications and glycemic control. Moreover, the severity of depressive symptoms is negatively correlated with comprehensive health-related QOL in patients with type 2 diabetes. Clinicians need to consider factors other than indices of metabolic control and diabetic complications, in determining the adverse effects of depressive symptoms on the physical QOL of patients with type 2 diabetes. PMID- 22293801 TI - Differential association between HLA and diffuse panbronchiolitis in Northern and Southern Chinese. AB - BACKGROUND: Diffuse panbronchiolitis (DPB) is a progressive inflammatory pulmonary disease that predominately affects East Asians. Genetic susceptibility to DPB is correlated with the human leukocyte antigens HLA-B54 in Japanese and HLA-A11 in Koreans. However, no systematic genetic study of DPB pathogenesis has been conducted in the Chinese population. The aim of this study was to investigate the possible association between HLA and disease susceptibility in Chinese patients with DPB. METHODS: A literature review of both Chinese and English language studies on Chinese DPB patients, published between 1983 and 2010, was conducted. Seventy subjects met the inclusion criteria and were retrospectively analyzed for HLA gene frequency according to geographic region. RESULTS: HLA-B54 frequency was significantly greater in DPB patients than in controls in the Northern Chinese group (35.7% vs. 4.6%, p=7.5*10(-7)). Although the HLA-B54 frequency was slightly increased in the Southern Chinese patients, the difference was not significant compared with control subjects (14.3% vs. 5.7%, p=0.28). The HLA-A11 frequency was significantly greater in DPB patients than controls in the Southern Chinese group (54.8% vs. 26.4%, p=0.009). Despite an increase of HLA-A11 frequency in the Northern Chinese group, no significant variation in HLA-A11 frequency was found compared with control subjects (42.9% vs. 30.8%, p=0.535). The HLA-A2 frequency was significantly decreased in DPB patients than in controls in the Southern Chinese group (22.9% vs. 66.0%, p=0.001). However, no significant difference in HLA-A2 frequency was found in the Northern Chinese group (50.0% vs. 46.9%, p=0.872). CONCLUSION: HLA-B54 and HLA A11 were positively associated with DPB in Northern and Southern Chinese, respectively. Population substructure may impact the genetic predisposition of DPB in China. PMID- 22293802 TI - Rapid recovery from congestive heart failure following successful radiofrequency catheter ablation in a patient with late onset of Wolff-Parkinson-White syndrome. AB - A 56-year-old man was admitted because of palpitations and dyspnea. A 12-lead electrocardiogram showed irregular wide QRS complex tachycardia with a slur at the initial portion of the QRS complex. He had preexisting long-standing persistent atrial fibrillation, but early excitation syndrome had never been noted. Chest X-ray showed heart enlargement and pulmonary congestion. He was diagnosed with late onset of Wolff-Parkinson-White syndrome, and congestive heart failure was probably caused by rapid ventricular response of atrial fibrillation through the accessory pathway. Emergency catheter ablation for the accessory pathway was undertaken, and heart failure was dramatically improved. PMID- 22293803 TI - Histopathological verification for successful ablation of mitral isthmus ventricular tachycardia complicated with cardiac sarcoidosis. AB - A 68-year-old man died a few days after catheter ablation of drug-resistant, monomorphic ventricular tachycardia (VT) complicated with cardiac sarcoidosis. The diagnosis of mitral isthmus VT was made from electrophysiological observations, including electro-anatomical activation and voltage map, pace mapping, entrainment mapping and ablation outcome. On autopsy of the heart, sarcoidic lesion with scattered fibrous tissue in the mitral isthmus was non transmural, and the surviving myocardium serving as the reentry circuit in the endomyocardium was isolated from the adjacent viable epimyocardium, enabling the sustenance of macroreentry across the mitral isthmus. Non-transmural lesions produced by RF delivery created a barrier sufficient to interrupt the myocardial bundles located in the mitral isthmus, eliminating the mitral isthmus VT. PMID- 22293804 TI - Nafcillin-induced bullous skin eruption with granulocytopenia in a patient with end-stage renal disease. AB - Nafcillin is an antibiotic used for infections due to penicillin-resistant Staphylococcus aureus. In general, the adverse reactions to nafcillin have not been frequent and serious. We report here a new type of adverse reaction to nafcillin in a patient with end-stage renal disease in whom nafcillin caused the unexpected complication of bullous drug eruption and subseqent neutropenia. Three weeks after the start of intravenous nafcillin for the treatment of peritoneal dialysis peritonitis, the patient developed blisters on his right ankle. These became progressive and widespread, with bullae affecting most of the body surface. In addition, neutropenia developed three days after the appearance of bullous skin lesions. Spontaneous recovery of skin lesions and neutropenia was observed after the withdrawal of naficillin. When treating patients with chronic renal failure, physicians should be aware of these rare but potentially severe adverse reactions. PMID- 22293805 TI - Tako-tsubo cardiomyopathy complicated by QRS prolongation. AB - A 68-year-old woman was admitted to our hospital due to sudden onset of dyspnea. On admission, electrocardiogram (ECG) showed T-wave inversion and QRS prolongation (120 msec) that were not found in her previous ECG. Chest X-ray showed pulmonary edema and cardiac enlargement. Left ventriculogram showed akinesis of the left ventricle except in the basal region. No significant coronary stenosis was found on angiogram. She was diagnosed as having tako-tsubo cardiomyopathy complicated by QRS prolongation. Intraaortic balloon pumping (IABP) was subsequently initiated for the treatment of acute heart failure. QRS prolongation was resolved immediately after the initiation of IABP, and left ventricular dysfunction was resolved within 9 days. She was discharged 14 days later. PMID- 22293806 TI - Rapidly progressive pulmonary fibrosis following the onset of diffuse alveolar hemorrhage in Sjogren's syndrome: an autopsy case report. AB - We report an autopsy case of a patient with Sjogren's syndrome (SjS) who presented with rapid progressive pulmonary fibrosis following the onset of diffuse alveolar hemorrhage (DAH) without cryoglobulinemia. Despite early and aggressive immunosuppressive therapy, pulmonary fibrosis progressed and the patient succumbed to his illness. An autopsy was performed and revealed DAH and interstitial pneumonia with a fibrotic nonspecific interstitial pneumonia pattern. We could not find any previously-reported underlying causes of DAH. The findings from this case suggest that DAH can occur as a pulmonary manifestation of SjS as well as other connective tissue diseases or vasculitis. PMID- 22293807 TI - Psychiatric symptoms in a patient with Churg-Strauss syndrome. AB - We report a case of Churg-Strauss syndrome (CSS) in a patient with multiple cerebral infarctions and psychotic symptoms. A 67-year-old man presented a high grade fever and delirium. He was clinically diagnosed with Churg-Strauss syndrome on the basis of the presence of asthma, neuropathy, blood eosinophilia, and increased myeloperoxidase-specific anti-neutrophil cytoplasmic antibody (MPO ANCA) activities. Though multiple cerebral infarctions are irreversible, this patient's psychiatric symptoms improved with steroid treatment. Psychiatric symptoms associated with CSS are very rare. PMID- 22293808 TI - Acute cardiac tamponade caused by the extension of multiple hepatic actinomycotic abscesses. AB - A 60-year-old man was diagnosed as multiple hepatic abscesses. Failure in the first empiric therapy led to extension into the pericardium, causing acute cardiac tamponade. Actinomyces species were not cultured from the pericardial effusion. The definitive diagnosis was acquired by ultrasound guided needle biopsy. PMID- 22293809 TI - Hypereosinophilic syndrome associated with simultaneous intracardiac thrombi, cerebral thromboembolism and pulmonary embolism. AB - The hypereosinophilic syndrome (HES) is a subcategory of idiopathic eosinophilia which is characterized by marked unexplained eosinophilia and evidence of tissue eosinophilia which leads to eosinophil-mediated organ damage. Cardiac and thromboembolic complications of HES are the common causes of mortality and morbidity. Here, we report a 54-year-old woman with HES who presented with simultaneously occurring cardiac thrombi, pulmonary embolism, and cerebrovascular thromboembolism. PMID- 22293810 TI - Precursor B-lymphoblastic lymphoma involving an intracardiac mass and myocardial infiltration: a case report. AB - We report the case of a 17-year-old man with precursor B-lymphoblastic lymphoma involving an intracardiac mass and myocardial infiltration. Intensified chemotherapy followed by autologous peripheral blood stem cell transplantation resulted in long-term complete remission for over 5 years. As the most frequent sites of B-lymphoblastic lymphoma involvement are the skin, soft tissue, bone, and lymph nodes, reports of cases harboring cardiac involvement are relatively few. This is a rare case of B-lymphoblastic lymphoma displaying cardiac involvement, in which cardiac infiltration was one of the initial manifestations. PMID- 22293811 TI - Differential diagnosis between intracranial dissemination of spinal cord astrocytoma and paraneoplastic limbic encephalitis. AB - We describe the clinical features of limbic encephalitis that developed after palliative spinal cordotomy in 2 patients with malignant thoracic astrocytoma. Both patients showed short-term memory loss, hallucinations of smells and psychiatric symptoms. Brain MRI on T2-weighted and fluid-attenuated inversion recovery sequences revealed high intensity lesions in bilateral temporal lobe areas. We considered that both patients had paraneoplastic limbic encephalitis associated with astrocytoma because of various clinical and radiological features. But the possibility of intracranial dissemination of astrocytoma could not be fully excluded. The differential diagnosis between intracranial dissemination of spinal cord astrocytoma and paraneoplastic limbic encephalitis may be sometimes difficult. PMID- 22293812 TI - Tophaceous gout in the cervical spine. AB - A 58-year-old woman with a three-year progressive history of chronic arthritis, had become disabled due to general malaise and fever. Her laboratory data revealed hyperuricemia and elevated levels of C-reactive protein. Neither rheumatoid factor nor anti-citrullinated peptide antibodies were present. We diagnosed her with tophaceous gout with uric crystalline revealed by the arthrocentesis of the elbow. (99m)Tc scintigraphy also disclosed a significant uptake in the cervical spine. The CT of the patient's cervical spine revealed significant bone erosion and destruction. We diagnosed the cervical involvement of gout based on the exclusion of infections and sarcoidosis. Rheumatologists should be aware of this rare association. PMID- 22293813 TI - Coronary stenosis, Crohn's disease and epicardial adipose tissue. PMID- 22293814 TI - Gastropleural fistula. PMID- 22293815 TI - Giant thrombus filling the pulmonary trunk. PMID- 22293816 TI - Giant tophi in the calf. PMID- 22293817 TI - Ruptured littoral cell angiosarcoma causing hemoperitoneum. PMID- 22293818 TI - Unilateral thalamic edema associated with deep venous thrombosis. PMID- 22293819 TI - Epstein-Barr virus encephalitis with a reversible splenial lesion. PMID- 22293820 TI - Abdominal cerebrospinal fluid pseudocyst surrounding a ventriculoperitoneal shunt. PMID- 22293821 TI - Differentiation between vertebral artery hypoplasia and occlusion. PMID- 22293822 TI - An imported case of disseminated cysticercosis and taeniasis. PMID- 22293823 TI - N-activated beta-lactams as versatile reagents for acyl carrier protein labeling. AB - Acyl carrier proteins are critical components of fatty acid and polyketide biosynthesis. Their primary function is to shuttle intermediates between active sites via a covalently bound phosphopantetheine arm. Small molecules capable of acylating this prosthetic group will provide a simple and reversible means of introducing novel functionality onto carrier protein domains. A series of N activated beta-lactams are prepared to examine site-specific acylation of the phosphopantetheine-thiol. In general, beta-lactams are found to be significantly more reactive than our previously studied beta-lactones. Selectivity for the holo over apo-form of acyl carrier proteins is demonstrated indicating that only the phosphopantetheine-thiol is modified. Incorporation of an N-propargyloxycarbonyl group provides an alkyne handle for conjugation to fluorophores and affinity labels. The utility of these groups for mechanistic interrogation of a critical step in polyketide biosynthesis is examined through comparison to traditional probes. In all, we expect the probes described in this study to serve as valuable and versatile tools for mechanistic interrogation. PMID- 22293824 TI - Expression changes in arrestin beta 1 and genetic variation in catechol-O methyltransferase are biomarkers for the response to morphine treatment in cancer patients. AB - Genetic differences in individuals with regard to opioid-receptor signaling create clinical difficulties for opioid treatment; consequently, useful pharmacodynamic and predictive biomarkers are needed. In this prospective study, we studied gene expression changes in peripheral blood leukocytes using a microarray and real-time RT-PCR analysis to identify pharmacodynamic biomarkers for monitoring the effect of morphine in a cohort of opioid-treatment-naive cancer patients. We also examined genetic variations in opioid receptor mu 1 (OPRM1, 118A->G) and catechol-O-methyltransferase (COMT, 472G->A) to evaluate predictive biomarkers of the treatment outcome of morphine. The plasma concentration of morphine was measured using a liquid chromatography-tandem mass spectrometry method. Microarray analysis revealed that the mRNA expression levels of arrestin beta 1 (ARRB1) were significantly down-regulated by morphine treatment. Real-time RT-PCR analysis against independent samples confirmed the results (P=0.003) and changes during treatment were negatively correlated with the plasma morphine concentration (R=-0.42). No correlation was observed between the genotype of OPRM1 and morphine treatment; however, the plasma concentration of morphine and the required dose of morphine were significantly lower for the A/A genotype of COMT (vs. A/G+G/G, P=0.008 and 0.03). We found that changes in the expression of ARRB1 may be a novel pharmacodynamic biomarker and the COMT 472G->A genotype may be a predictive biomarker of the response to morphine treatment. PMID- 22293825 TI - Mid-dermal elastolysis: another dermatological clue to autoimmunity? PMID- 22293826 TI - A single injection of a novel kappa opioid receptor agonist salvinorin A attenuates the expression of cocaine-induced behavioral sensitization in rats. AB - Kappa opioid receptor (KOPr) activation antagonizes many cocaine-related behaviors but adverse side-effects such as sedation, dysphoria, and depression limit their therapeutic use. Recently, salvinorin A (Sal A), a naturally occurring KOPr agonist, has been shown to attenuate cocaine-induced drug seeking in a model of relapse in rats. The present study evaluated the effects of acute Sal A exposure on cocaine-induced hyperactivity and cocaine sensitization in rats. Acute treatment with a dose of Sal A that decreased drug seeking in a previous study (0.3 mg/kg) significantly attenuated the expression of cocaine sensitization. This dose of Sal A failed to affect spontaneous locomotion or to produce a conditioned taste aversion to a novel-tasting saccharin solution. However, Sal A decreased climbing and swimming time and increased time spent immobile in the forced swim test. These findings indicate that Sal A, just like traditional KOPr agonists, attenuates cocaine-induced behavioral sensitization but does not produce the adverse effect of conditioned aversion, suggesting improved potential compliance. However, prodepressive effects were also produced and these effects may limit the therapeutic potential. PMID- 22293827 TI - Baseline susceptibility of primary HIV-2 to entry inhibitors. AB - BACKGROUND: The baseline susceptibility of primary HIV-2 to maraviroc (MVC) and other entry inhibitors is currently unknown. METHODS: The susceptibility of 19 HIV-2 isolates obtained from asymptomatic and AIDS patients and seven HIV-1 clinical isolates to the fusion inhibitors enfuvirtide (ENF) and T-1249, and to the coreceptor antagonists AMD3100, TAK-779 and MVC, was measured using a TZM-bl cell-based assay. The 50% inhibitory concentration (IC(50)), 90% inhibitory concentration (IC(90)) and dose-response curve slopes were determined for each drug. RESULTS: ENF and T-1249 were significantly less active on HIV-2 than on HIV 1 (211- and 2-fold, respectively). AMD3100 and TAK-779 inhibited HIV-2 and HIV-1 CXCR4 tropic (X4) and CCR5 tropic (R5) variants with similar IC(50) and IC(90) values. MVC, however, inhibited the replication of R5 HIV-2 variants with significantly higher IC(90) values (42.7 versus 9.7 nM; P<0.0001) and lower slope values (0.7 versus 1.3; P<0.0001) than HIV-1. HIV-2 R5 variants derived from AIDS patients were significantly less sensitive to MVC than variants from asymptomatic patients, this being inversely correlated with the absolute number of CD4(+) T cells. CONCLUSIONS: T-1249 is a potent inhibitor of HIV-2 replication indicating that new fusion inhibitors might be useful to treat HIV-2 infection. Coreceptor antagonists TAK-779 and AMD3100 are also potent inhibitors of HIV-2 replication. The reduced sensitivity of R5 variants to MVC, especially in severely immunodeficient patients, indicates that the treatment of HIV-2-infected patients with MVC might require higher dosages than those used in HIV-1 patients, and should be adjusted to the disease stage. PMID- 22293828 TI - Preclinical evaluation of the antineoplastic efficacy of 7-(2 hydroxyethyl)theophylline on melanoma cancer cells. AB - Differentiation-based therapeutics are an underutilized but potentially a significant option for cancer treatment. The effect of methylxanthines on melanoma cell differentiation has been well documented. We report the in-vitro and in-vivo anticancer potential of a theophylline analogue, 7-(2 hydroxyethyl)theophylline (HET), on murine B16-F10 and human Sk-Mel 110 metastatic melanoma cell lines. The effects on cell proliferation were related to the induction of differentiation, demonstrated as increased intracellular transglutaminase activity. The involvement of this methylxanthine in the control of the in-vitro adhesion and in the in-vivo metastastic spread of melanoma cells was further investigated. HET oral administration of C57BL6/N mice intravenously injected with B16-F10 cells markedly reduced lung metastases frequency. The overall results demonstrated that HET possesses a remarkable in-vivo antimetastatic capability. PMID- 22293829 TI - RNA driving the epigenetic bus. PMID- 22293830 TI - Rac1 gets fattier. PMID- 22293831 TI - A structural road map to unveil basal body composition and assembly. PMID- 22293832 TI - Welcome to the iPDA! PMID- 22293833 TI - Iontophoretic delivery of acyclovir: intradermal drug monitoring using microdialysis and quantification by skin extraction. AB - The objective of this study was to investigate the effect of iontophoresis on the intradermal and transdermal delivery of acyclovir using hairless rat skin on a vertical Franz diffusion cell. In this study, cathodal iontophoretic delivery of acyclovir from a pH 11 formulation was explored. The effects of time of iontophoresis (10 min, 1 h, and 4 h) and current density (0.2, 0.3, and 0.5 mA/cm(2)) on skin permeation were examined. In vitro dermal microdialysis was performed to identify the drug depot formed in the dermis during iontophoresis. Acyclovir delivery into the receptor compartment was not influenced by current density or duration of current application. However, greater drug levels were delivered into the skin as a function of time of current application to form a drug depot. These results were further confirmed by in vitro dermal microdialysis in which higher drug levels were observed in dialysate in the 4 h iontophoresis group due to higher drug levels delivered into the skin layers as compared to 1 h iontophoresis group. Short duration iontophoresis enhanced acyclovir delivery into the skin layers rapidly and thus may be beneficial to improve treatment for cold sores (herpes labialis infection). Microdialysis could be used as a tool to simultaneously monitor drug levels in the tissue's interstitial fluid in real time in an in vitro setting. LAY ABSTRACT: The objective of this study was to investigate the effect of current on the delivery of acyclovir into and across the skin using hairless rat skin mounted on glass diffusion cells. Acyclovir was delivered under negative polarity from a formulation with a very basic pH. The effect of current intensity and duration of application on delivery of acyclovir was investigated. The amount in the skin was also determined by inserting a probe into the skin with a semipermeable membrane that allows sampling of the drug that has entered the skin. When the current intensity or duration was increased, greater drug levels were seen in the skin but not across the skin. It was found that even short duration of current application can deliver acyclovir into the skin and this has potential use for treatment of cold sores. PMID- 22293834 TI - Root Cause Investigation of Rubber Seal Cracking in Pre-filled Cartridges: Ozone and Packaging Effects. AB - Pre-filled syringes/cartridges as primary packaging for parenterally delivered biopharmaceutical liquids consist of multiple components, including containers made of glass or plastic, and stoppers/plungers and disk seals (septa) made of rubber materials. Cracking of rubber components may be cosmetically unacceptable and in extreme cases may compromise enclosure integrity. The purpose of this study was to investigate the root cause of septum cracking and evaluate parameters/solutions to delay or prevent cracking from occurring. Custom-made chambers capable of tightly controlling ozone levels were assembled to deliberately create septum cracks. Cracks were qualitatively assessed by optical microscopy and quantified using image analysis by ImageJ. The results confirmed that ozone attack is the root cause of septum cracking during storage, and the stress-the result of crimping on the glass cartridge by the aluminum lined seal made the septum particularly vulnerable to ozone attack. Ozone concentration as low as 10-40 ppb (levels routinely detected on a busy street) could crack the stressed septum in hours while days of ozone exposure at 50 ppm could not cause the unstressed septum to crack. Under ozone attack cracks initially grow in length and width uniformly across the stressed area and then stop progressing, perhaps due to residual stress release. Although the use of impermeable barriers could prevent cracking completely, this study suggested that any form of packaging barriers, including a highly permeable Tyvek(r) sheet, could postpone cracking by slowing down ozone diffusion and convection. We demonstrate that simple double packaging-placing the Tyvek(r)-lidded blister tray in a cardboard carton-could sufficiently protect the stressed septum for years in a surrounding environment with ozone at normal indoor levels (<=2 ppb). LAY ABSTRACT: Pre filled syringes/cartridges as primary packaging for parenterally delivered biopharmaceutical liquids contain multiple components, including a disk seal (septum) made of rubber materials. Cracking of rubber components may be cosmetically unacceptable and in extreme cases may compromise enclosure integrity. The septum, if not appropriately packaged, might crack under uncontrolled storage environment. The purpose of this study was to investigate the root cause of septum cracking and evaluate parameters/solutions to delay or prevent cracking from occurring. Custom-made chambers capable of tightly controlling ozone levels were assembled to deliberately create septum cracks. The results confirmed that ozone attack is the root cause of septum cracking during storage, and the stress-the result of crimping on the glass cartridge by the aluminum lined seal-made the septum particularly vulnerable to ozone attack. Ozone concentration as low as 10-40 ppb (levels routinely detected on a busy street) could crack the stressed septum in hours. Although the use of impermeable barriers could prevent cracking completely, this study suggested that any form of packaging barriers, including a highly permeable Tyvek(r) sheet, could postpone cracking by slowing down ozone diffusion and convection. This investigation will raise awareness of manufacturers of pre-filled cartridge/syringe parenteral products to storage and packaging requirements for the long-term physical stability of cartridge components as small as the rubber septum. PMID- 22293835 TI - Headspace Moisture Mapping and the Information That Can Be Gained about Freeze Dried Materials and Processes. AB - Regulatory authorities require proof that lyophilization (freeze drying) cycles have been developed logically and demonstrate uniformity. One measure of uniformity can be consistency of residual water content throughout a batch. In primary drying, heat transfer is effected by gaseous convection and conduction as well as the degree of shelf contact and evenness of heat applied; therefore residual water can be affected by container location, degree of container/tray/shelf contact, radiative heating, packing density, product formulation, and the cycle conditions themselves. In this study we have used frequency modulation spectroscopy (FMS) to create a map of headspace moisture (HSM) for 100% of vials within a number of freeze-dried batches. Karl Fischer (KF)/HSM correlations were investigated in parallel with the moisture mapping studies. A clear, linear relationship was observed between HSM and KF values for vials containing freeze-dried sucrose, implying a relatively straightforward interaction between water and the lyophilized cake for this material. Mannitol demonstrated a more complex correlation, with the interaction of different crystalline forms giving important information on the uniformity of the material produced. It was observed that annealing had a significant impact on the importance of heat transfer by conduction for vials in direct and non-direct contact with the shelf. Moisture mapping of all vials within the freeze dryer enabled further information to be obtained on the relationship of the formulation, process conditions, and equipment geometry on the intra-batch variability in HSM level. The ability of FMS to allow 100% inspection could mean that this method could play an important part in process validation and quality assurance. LAY ABSTRACT: Lyophilization, also known as freeze drying, is a relatively old technique that has been used in its most basic form for thousands of years (e.g., preservation of fish and meat products). In its more advanced form it is used to preserve many medical products; for example, many vaccines are not stable in solution and therefore need to be dried to allow long-term storage. In order to produce a freeze-dried vaccine, a complex understanding of the processes and critical temperatures is required. Once these have been understood, the material is dried to give relatively low moisture content (e.g., 2% w/w.) This low moisture content is critical for the long-term stability of the product, allowing doctors/chemists to store these goods on site for use when required. This research paper provides further information on a technique called frequency modulation spectroscopy (FMS) that has been used to map the moisture variation across samples within a freeze dryer, enabling us to increase our understanding of the role various processing conditions play on the relationship between the product and water. It has demonstrated its potential application for 100% batch monitoring and the validation of a system or assessment of changes made. This method could assist in improving quality assurance and ultimately the final product that reaches the consumer. PMID- 22293836 TI - Variability in syringe components and its impact on functionality of delivery systems. AB - Prefilled syringes and autoinjectors are becoming increasingly common for parenteral drug administration primarily due to the convenience they offer to the patients. Successful commercialization of such delivery systems requires thorough characterization of individual components. Complete understanding of various sources of variability and their ranking is essential for robust device design. In this work, we studied the impact of variability in various primary container and device components on the delivery forces associated with syringe injection. More specifically, the effects of barrel size, needle size, autoinjector spring force, and frictional forces have been evaluated. An analytical model based on underlying physics is developed that can be used to fully characterize the design space for a product delivery system. LAY ABSTRACT: Use of prefilled syringes (syringes prefilled with active drug) is becoming increasingly common for injectable drugs. Compared to vials, prefilled syringes offer higher dose accuracy and ease of use due to fewer steps required for dosage. Convenience to end users can be further enhanced through the use of prefilled syringes in combination with delivery devices such as autoinjectors. These devices allow patients to self-administer the drug by following simple steps such as pressing a button. These autoinjectors are often spring-loaded and are designed to keep the needle tip shielded prior to injection. Because the needle is not visible to the user, such autoinjectors are perceived to be less invasive than syringes and help the patient overcome the hesitation associated with self-administration. In order to successfully develop and market such delivery devices, we need to perform an in-depth analysis of the components that come into play during the activation of the device and dose delivery. Typically, an autoinjector is activated by the press of a button that releases a compressed spring; the spring relaxes and provides the driving force to push the drug out of the syringe and into the site of administration. Complete understanding of the spring force, syringe barrel dimensions, needle size, and drug product properties is essential for robust device design. It is equally important to estimate the extent of variability that exists in these components and the resulting impact it could have on the performance of the device. In this work, we studied the impact of variability in syringe and device components on the delivery forces associated with syringe injection. More specifically, the effect of barrel size, needle size, autoinjector spring force, and frictional forces has been evaluated. An analytical model based on underlying physics is developed that can be used to predict the functionality of the autoinjector. PMID- 22293837 TI - Detection of silicone oil leakages in freeze dryers. AB - As a small leakage from the silicone oil tubes in pharmaceutical freeze dryers may go undetected for several cycles, it provides a major threat to both product safety and the economic performance of such installations. A properly mounted mass spectrometer offers a non-invasive method of detecting the smallest amounts of silicone oil down to 1 ppm. Additionally the system will improve leak testing procedures and can also be used as a process analytical technology tool to improve process control. LAY ABSTRACT: Drugs, and in particular parenterals, need to have a very high level of purity. A production process such as freeze drying carries the inherent risk of contamination by process fluids. This should not happen during routine production, but in the event of a malfunction small amounts of these fluids may contaminate the drug product. The purpose of this paper is to introduce a method which is able to detect such malfunctions before they can develop into a risk for drug purity and ultimately patient safety. PMID- 22293838 TI - Vacuum decay container closure integrity leak test method development and validation for a lyophilized product-package system. AB - A leak test performed according to ASTM F2338-09 Standard Test Method for Nondestructive Detection of Leaks in Packages by Vacuum Decay Method was developed and validated for container-closure integrity verification of a lyophilized product in a parenteral vial package system. This nondestructive leak test method is intended for use in manufacturing as an in-process package integrity check, and for testing product stored on stability in lieu of sterility tests. Method development and optimization challenge studies incorporated artificially defective packages representing a range of glass vial wall and sealing surface defects, as well as various elastomeric stopper defects. Method validation required 3 days of random-order replicate testing of a test sample population of negative-control, no-defect packages and positive-control, with defect packages. Positive-control packages were prepared using vials each with a single hole laser-drilled through the glass vial wall. Hole creation and hole size certification was performed by Lenox Laser. Validation study results successfully demonstrated the vacuum decay leak test method's ability to accurately and reliably detect those packages with laser-drilled holes greater than or equal to approximately 5 MUm in nominal diameter. All development and validation studies were performed at Whitehouse Analytical Laboratories in Whitehouse, NJ, under the direction of consultant Dana Guazzo of RxPax, LLC, using a VeriPac 455 Micro Leak Test System by Packaging Technologies & Inspection (Tuckahoe, NY). Bristol Myers Squibb (New Brunswick, NJ) fully subsidized all work. LAY ABSTRACT: A leak test performed according to ASTM F2338-09 Standard Test Method for Nondestructive Detection of Leaks in Packages by Vacuum Decay Method was developed and validated to detect defects in stoppered vial packages containing lyophilized product for injection. This nondestructive leak test method is intended for use in manufacturing as an in-process package integrity check, and for testing product stored on stability in lieu of sterility tests. Test method validation study results proved the method capable of detecting holes laser-drilled through the glass vial wall greater than or equal to 5 MUm in nominal diameter. Total test time is less than 1 min per package. All method development and validation studies were performed at Whitehouse Analytical Laboratories in Whitehouse, NJ, under the direction of consultant Dana Guazzo of RxPax, LLC, using a VeriPac 455 Micro Leak Test System by Packaging Technologies & Inspection (Tuckahoe, NY). Bristol Myers Squibb (New Brunswick, NJ) fully subsidized all work. PMID- 22293839 TI - Proposal on How To Conduct a Biopharmaceutical Process Failure Mode and Effect Analysis (FMEA) as a Risk Assessment Tool. AB - With the publication of the quality guideline ICH Q9 "Quality Risk Management" by the International Conference on Harmonization, risk management has already become a standard requirement during the life cycle of a pharmaceutical product. Failure mode and effect analysis (FMEA) is a powerful risk analysis tool that has been used for decades in mechanical and electrical industries. However, the adaptation of the FMEA methodology to biopharmaceutical processes brings about some difficulties. The proposal presented here is intended to serve as a brief but nevertheless comprehensive and detailed guideline on how to conduct a biopharmaceutical process FMEA. It includes a detailed 1-to-10-scale FMEA rating table for occurrence, severity, and detectability of failures that has been especially designed for typical biopharmaceutical processes. The application for such a biopharmaceutical process FMEA is widespread. It can be useful whenever a biopharmaceutical manufacturing process is developed or scaled-up, or when it is transferred to a different manufacturing site. It may also be conducted during substantial optimization of an existing process or the development of a second generation process. According to their resulting risk ratings, process parameters can be ranked for importance and important variables for process development, characterization, or validation can be identified. LAY ABSTRACT: Health authorities around the world ask pharmaceutical companies to manage risk during development and manufacturing of pharmaceuticals. The so-called failure mode and effect analysis (FMEA) is an established risk analysis tool that has been used for decades in mechanical and electrical industries. However, the adaptation of the FMEA methodology to pharmaceutical processes that use modern biotechnology (biopharmaceutical processes) brings about some difficulties, because those biopharmaceutical processes differ from processes in mechanical and electrical industries. The proposal presented here explains how a biopharmaceutical process FMEA can be conducted. It includes a detailed 1-to-10-scale FMEA rating table for occurrence, severity, and detectability of failures that has been especially designed for typical biopharmaceutical processes. With the help of this guideline, different details of the manufacturing process can be ranked according to their potential risks, and this can help pharmaceutical companies to identify aspects with high potential risks and to react accordingly to improve the safety of medicines. PMID- 22293840 TI - Pulmonary drug delivery: novel pharmaceutical technologies breathe new life into the lungs. AB - Pulmonary drug delivery is a developing technology in which medication is inhaled through the lungs and enters the bloodstream through the alveolar epithelium. Pulmonary drug delivery provides a noninvasive, alternative method to subcutaneous injection, and also intravenous injection. The delivery device plays a major role in the efficiency of pulmonary delivery, and great strides have been made in the development of new devices in recent years. The devices most commonly used for respiratory delivery, including nebulizers, metered-dose inhalers, and dry powder inhalers, can all be adapted for use with protein/peptide drugs. The choice of device will depend on the drug, the formulation, the site of action, and the pathophysiology of the lungs. While a great deal of recent research has focused on the development of novel devices, attention must now be paid to the formulation of these macromolecular drugs. The emphasis in this review will be on targeting of drugs by inhalation using carriers (such as liposomes, microspheres, microparticles, and nanoparticles) and ligands. PMID- 22293841 TI - Burkholderia cepacia: This Decision Is Overdue. AB - This is the third in a series of seven articles discussing the Recall Root Cause Research project conducted by the Division of Manufacturing and Product Quality, Center for Drug Evaluation and Research. This paper reviews the regulatory and scientific impact of a common and recurring opportunistic pathogen, Burkholderia cepacia. B. cepacia is comprised of closely related species called Burkholderia cepacia complex, which has contaminated many finished pharmaceutical products and environments used to manufacture pharmaceuticals. This review includes a brief perspective as described in several U.S. Food and Drug Administration (FDA) documents, and assesses root cause using product recall reports and FDA Establishment Inspection Reports. We identify several possible points of origin for microbial contamination. This discussion also includes concern with anomalies in test methods that may influence B. cepacia measurement. The issue of objectionable microorganisms and whether B. cepacia can readily be included in a compendial chapter is briefly discussed. Finally, this paper underscores that drugs contaminated with B. cepacia pose a serious threat to susceptible patients, particularly those with cystic fibrosis or who are otherwise immunocompromised. It is therefore important to prevent B. cepacia from contaminating pharmaceutical manufacturing environments, raw materials, and finished products. LAY ABSTRACT: Burkholderia cepacia is a species of bacterium that is commonly found in natural environments such as soil, water, rhizosphere and agriculture products. The species name represents a group of closely related organisms. These bacteria have contaminated many drug products and can create public health concerns. Pharmaceutical products that are contaminated with B. cepacia may pose serious consequences to vulnerable patients (e.g., compromised immune system). Preventing B. cepacia contamination in drugs by addressing the potential sources of this bacteria in a drug manufacturing operation is an important public health goal. This review highlights potential sources of B. cepacia species as they relate to U.S. Food and Drug Administration findings recorded in data from Establishment Inspection Reports and Warning Letters. PMID- 22293842 TI - Women with and without metabolic disorder differ in their gut microbiota composition. AB - The aim of this study was to investigate whether overweight/obese women in metabolic disorder group (MDG, n = 27) differ in their gut microbiota composition from overweight/obese women in non-metabolic disorder group (NMDG, n = 47) and normal weight women group (NWG, n = 11). Gut microbiota was profiled from fecal samples by 16S rRNA fluorescence in situ hybridization and flow cytometry in 85 premenopausal women. Body composition was measured by bioimpedance, and dietary intakes were collected via food diaries. Standard procedures were used to assess plasma glucose, serum insulin, lipids, and inflammatory status. We found that the proportion of bacteria belonging to Eubacterium rectale-Clostridium coccoides group, indicating efficient energy harvest from nutrients in gut, was higher in MDG compared to NMDG and NWG, while no difference was found between NMDG and NWG. The proportion of Eubacterium rectale-Clostridium coccoides group correlated positively with weight, BMI, total fat, fat mass percentage (FM%), visceral fat area, and serum triglycerides, and negatively with high-density lipoprotein (HDL). Our results indicate that certain members of Eubacterium rectale Clostridium coccoides group are associated with obesity-related MDs not obesity per se. PMID- 22293843 TI - Modulation of the differentiation of dental pulp stem cells by different concentrations of beta-glycerophosphate. AB - Dentinogenesis is a necessary prerequisite for dental tissue engineering. One of the steps for dentinogenesis is to obtain large quantities of highly purified odontoblasts. Therefore, we have undertaken an experiment applying different concentrations of beta-glycerophosphate (beta-GP) to induce the differentiation of dental pulp stem cells (DPSCs) in a long-term 28-day culture. In the meanwhile, we have studied the time- and maturation-dependent expression of matrix extracellular phosphoglycoprotein (MEPE) and that of the odontoblast-like marker-dentin sialoprotein (DSP), in order to investigate an optimized mineralized condition. Western blot results revealed that the expression of DSP became lower when accompanied by the increase of the beta-GP concentration, and there was also an influence on MEPE expression when different concentrations of beta-GP were applied. Meanwhile, the mineralized groups had an inhibitory function on the expression of MEPE as compared with the control group. Above all, all experimental groups successfully generated mineralized nodules by Alizarin Red S and the 5 mM beta-GP group formed more mineralized nodules quantitated using the CPC extraction method. In conclusion, there is a significant modulation of the beta-GP during the differentiation of the DPSCs. The degree of odontoblast differentiation is beta-glycerophosphate concentration dependent. A low concentration of beta-GP (5 mM) has been shown to be the optimal concentration for stimulating the maturation of the DPSCs. Moreover, MEPE accompanied with DSP clearly demonstrates the degree of the differentiation. PMID- 22293844 TI - Synthesis of novel IP agonists via N-aminoethyl cyclic amines prepared by decarboxylative ring-opening reactions. AB - An efficient synthesis of a highly potent and selective IP (PGI(2) receptor) agonist that is not structurally analogous to PGI(2) is described. This synthesis is accomplished through the following key steps: Nucleophilic ring-opening of 3 (4-chlorophenyl)-oxazolidin-2-one prepared by a one-pot procedure with 4 piperidinol and selective O-alkylation of 1-(2-(4 chlorophenylamino)ethyl)piperidin-4-ol. The obtained compound is a potent and selective IP agonist displaying a long duration of action. PMID- 22293845 TI - Chiroptical switches: applications in sensing and catalysis. AB - Chiroptical switches have found application in the detection of a multitude of different analytes with a high level of sensitivity and in asymmetric catalysis to offer switchable stereoselectivity. A wide range of scaffolds have been employed that respond to metals, small molecules, anions and other analytes. Not only have chiroptical systems been used to detect the presence of analytes, but also other properties such as oxidation state and other physical phenomena that influence helicity and conformation of molecules and materials. Moreover, the tunable responses of many such chiroptical switches enable them to be used in the controlled production of either enantiomer or diastereomer at will in many important organic reactions from a single chiral catalyst through selective use of a low-cost inducer: Co-catalysts (guests), metal ions, counter ions or anions, redox agents or electrochemical potential, solvents, mechanical forces, temperature or electromagnetic radiation. PMID- 22293846 TI - Synthesis, characterization and cytotoxicity of new rotundic acid derivatives. AB - Rotundic acid (RA, 1), a natural compound, exhibits potent tumor cell growth inhibiting properties. To date there are no reports on derivatives of RA. Furthermore, the 28-COOH position of RA might make it unstable and induced serious gastrointestinal side effects when it was applied in vivo. Therefore, in order to explore and make use of this compound, eight new amino acid derivatives of RA at the 28-COOH position were synthesized and evaluated for their cytotoxicities in vitro on three tumor cell lines including A375, HepG2 and NCI H446. As a result, a few of these new amino acid derivatives showed stronger cytotoxicity. Compound 5a was found to have the best inhibition activity on the three tested human tumor cell lines with IC(50) values of less than 10 MUM compared with RA treatment. Meanwhile, the cytotoxicity of compound 6b was significantly higher than that of RA on the A375 cell line and almost the same as RA on the HepG2 and NCI-H446 cell lines. Hence, compounds 5a and 6b may serve as potential lead compounds for the development of new anti-tumor drugs. PMID- 22293847 TI - Microwave-assisted synthesis of new substituted anilides of quinaldic acid. AB - In this study a one step method for the preparation of substituted anilides of quinoline-2-carboxylic acid was developed. This efficient innovative approach is based on the direct reaction of an acid or ester with substituted anilines using microwave irradiation. The optimized method was used for the synthesis of a series of eighteen substituted quinoline-2-carboxanilides. The molecular structure of N-(4-bromophenyl)quinoline-2-carboxamide as a model compound was determined by single-crystal X-ray diffraction. It crystallizes in the monoclinic space group with four molecules within the unit cell and the total structure of the compound can be described as "a slightly screwed boat". PMID- 22293848 TI - New nano-architectures of mesoporous silica spheres analyzed by advanced electron microscopy. AB - Using template-containing silica microspheres as a precursor, novel ordered mesoporous silica nanoparticles with a narrow pore size distribution and high crystallinity have been synthesized by various hydrothermal merging processes. Several architectures like chains, dumbbells, triangles, squares and flowers have been discovered. The linking mechanisms of these interacting silica spheres leading to the formation of ordered nano-structures are studied by HRTEM, HAADF STEM and electron tomography and a plausible model is presented for several merging processes. PMID- 22293849 TI - Elastoderma: an uncommon cause of acquired hyperextensible skin. PMID- 22293850 TI - Reduced levels of p15INK4b, p16INK4a, p21cip1 and p27kip1 in pancreatic carcinoma. AB - Pancreatic carcinoma is one of the leading causes of cancer mortality worldwide, although the molecular mechanisms of this disease are poorly understood. The aim of this study was to examine the expression of cyclin-dependent kinase inhibitors (CDKIs) and the epigenetic modifications in the promoters of these genes. We also evaluated the correlation between the methylation status of CDKI genes and smoking habit in clinical pancreatic carcinoma specimens. Western blotting and real-time PCR were performed to assess CDKI expression. Methylation-specific PCR was carried out to examine the methylation status of the promoters of CDKI genes. In this study, we revealed that reduced levels of the CDKI proteins, p15INK4b, p16INK4a, p21cip1 and p27kip1, are a prominent feature of pancreatic carcinoma patients. The DNA hypermethylation of the promoter was observed in 40% (2 of 5) of the p15INK4b genes, 60% (3 of 5) of the p16INK4a genes and 60% of the p21cip1 genes, which markedly correlated with their decreased mRNA expression. No hypermethylation was detected in the p27kip1 gene promoter in 5 pancreatic carcinoma patients with markedly decreased expression of p27kip1 mRNA, suggesting an alternative mechanism of p27kip in these patients. In this study, patients with a smoking habit displayed methylation of 2 CDKI genes in their pancreatic carcinoma specimens. We concluded that epigenetic modification via hypermethylation represents a critical mechanism for the inactivation of CDKI genes in pancreatic carcinoma. PMID- 22293851 TI - A CD31-derived peptide prevents angiotensin II-induced atherosclerosis progression and aneurysm formation. AB - AIMS: The loss of the inhibitory receptor CD31 on peripheral T lymphocytes is associated with the incidence of atherosclerotic complications such as abdominal aortic aneurysms (AAA) in patients and plaque thrombosis in mice. However, we have recently discovered that a small fragment of extracellular CD31 remains expressed on the surface of the apparently 'CD31-negative' T-cells and that it is possible to restore the CD31-mediated T-cell inhibition in vivo by using a synthetic CD31-derived peptide. Here, we wanted to evaluate the therapeutic potential of the peptide in an experimental model of accelerated atherosclerosis and AAA formation. METHODS AND RESULTS: The effect of the murine CD31-derived peptide (aa 551-574, 1.5 mg/kg/day, sc) was evaluated on the extent of atherosclerotic plaques and the incidence of AAA in 28-week-old apolipoprotein E knockout mice (male, n >= 8/group) submitted to chronic angiotensin II infusion. The therapeutic mechanisms of the peptide were assessed by evaluating its effect on immune cell functions in vivo and in vitro. The prevalence of angiotensin II induced AAA correlated with the loss of extracellular CD31 on T-cells. CD31 peptide treatment reduced both aneurysm formation and plaque size (P < 0.05 vs. control). Protection was associated with reduced perivascular leucocyte infiltration and T-cell activation in vivo. Functional in vitro studies showed that the peptide is able to suppress both T-cell and macrophage activation. CONCLUSION: CD31 peptides could represent a new class of drugs intended to prevent the inflammatory cell processes, such as those underlying progression of atherosclerosis and development of AAA. PMID- 22293853 TI - Expression of mung bean pectin acetyl esterase in potato tubers: effect on acetylation of cell wall polymers and tuber mechanical properties. AB - A mung bean (Vigna radiata) pectin acetyl esterase (CAA67728) was heterologously expressed in tubers of potato (Solanum tuberosum) under the control of the granule-bound starch synthase promoter or the patatin promoter in order to probe the significance of O-acetylation on cell wall and tissue properties. The recombinant tubers showed no apparent macroscopic phenotype. The enzyme was recovered from transgenic tubers using a high ionic strength buffer and the extract was active against a range of pectic substrates. Partial in vivo de acetylation of cell wall polysaccharides occurred in the transformants, as shown by a 39% decrease in the degree of acetylation (DA) of tuber cell wall material (CWM). Treatment of CWM using a combination of endo-polygalacturonase and pectin methyl esterase extracted more pectin polymers from the transformed tissue compared to wild type. The largest effect of the pectin acetyl esterase (68% decrease in DA) was seen in the residue from this extraction, suggesting that the enzyme is preferentially active on acetylated pectin that is tightly bound to the cell wall. The effects of acetylation on tuber mechanical properties were investigated by tests of failure under compression and by determination of viscoelastic relaxation spectra. These tests suggested that de-acetylation resulted in a stiffer tuber tissue and a stronger cell wall matrix, as a result of changes to a rapidly relaxing viscoelastic component. These results are discussed in relation to the role of pectin acetylation in primary cell walls and its implications for industrial uses of potato fibres. PMID- 22293854 TI - Root phototropism: from dogma to the mechanism of blue light perception. AB - In roots, the "hidden half" of all land plants, gravity is an important signal that determines the direction of growth in the soil. Hence, positive gravitropism has been studied in detail. However, since the 19th century, the response of roots toward unilateral light has also been analyzed. Based on studies on white mustard (Sinapis alba) seedlings, botanists have concluded that all roots are negatively phototropic. This "Sinapis-dogma" was refuted in a seminal study on root phototropism published a century ago, where it was shown that less then half of the 166 plant species investigated behave like S. alba, whereas 53% displayed no phototropic response at all. Here we summarize the history of research on root phototropism, discuss this phenomenon with reference to unpublished data on garden cress (Lepidium sativum) seedlings, and describe the effects of blue light on the negative bending response in Thale cress (Arabidopsis thaliana). The ecological significance of root phototropism is discussed and the relationships between gravi- and phototropism are outlined, with respect to the starch statolith-theory of gravity perception. Finally, we present an integrative model of gravi- and blue light perception in the root tip of Arabidopsis seedlings. This hypothesis is based on our current view of the starch-statolith-concept and light sensing via the cytoplasmic red/blue light photoreceptor phytochrome A and the plasma membrane-associated blue light receptor phototropin-1. Open questions and possible research agendas for the future are summarized. PMID- 22293855 TI - Transcriptional activity of Hyacinthus orientalis L. female gametophyte cells before and after fertilization. AB - We characterized three phases of Hyacinthus orientalis L. embryo sac development, in which the transcriptional activity of the cells differed using immunolocalization of incorporated 5'-bromouracil, the total RNA polymerase II pool and the hypo- (initiation) and hyperphosphorylated (elongation) forms of RNA Pol II. The first stage, which lasts from the multinuclear stage to cellularization, is a period of high transcriptional activity, probably related to the maturation of female gametophyte cells. The second stage, encompassing the period of embryo sac maturity and the progamic phase, involves the transcriptional silencing of cells that will soon undergo fusion with male gametes. During this period in the hyacinth egg cell, there are almost no newly formed transcripts, and only a small pool of RNA Pol II is present in the nucleus. The transcriptional activity of the central cell is only slightly higher than that observed in the egg cell. The post-fertilization stage is related to the transcriptional activation of the zygote and the primary endosperm cell. The rapid increase in the pool of newly formed transcripts in these cells is accompanied by an increase in the pool of RNA Pol II, and the pattern of enzyme distribution in the zygote nucleus is similar to that observed in the somatic cells of the ovule. Our data, together with the earlier results of Piecinski et al. (2008), indicate post-fertilization synthesis and the maturation of numerous mRNA transcripts, suggesting that fertilization in H. orientalis induces the activation of the zygote and endosperm genomes. PMID- 22293856 TI - ProstaCaid inhibits tumor growth in a xenograft model of human prostate cancer. AB - We have recently demonstrated that the dietary supplement ProstaCaid (PC) inhibits growth and invasive behavior of PC-3 human prostate cancer cells in vitro. In the present study, we evaluated toxicity and whether PC suppresses growth of prostate cancer in a xenograft model of human prostate cancer cells implanted in mice. Here, we show that an oral administration of PC (100, 200 and 400 mg/kg) did not affect body weight or activity of liver enzymes (ALT, AST) and did not show any sign of toxicity in liver, spleen, kidney, lung and heart tissues in mice. In addition, PC treatment resulted in the inhibition of tumor volumes (1024.6 +/- 378.6 vs. 749.3 +/- 234.3, P<0.001) in a xenograft model of prostate cancer with human hormone refractory (independent) PC-3 prostate cancer cells. Moreover, qRT-PCR analysis demonstrated significant upregulation of expression of CDKN1A (p21) and inhibition of expression of IGF2, NR2F2 and PLAU (uPA) genes by an oral administration of PC in prostate cancer xenografts. Our study demonstrates that the concentrations of the dietary supplement ProstaCaid tested did not show signs of toxicity, and its oral application has significant anticancer activity in vivo and can be considered as an alternative treatment for prostate cancer patients. PMID- 22293857 TI - Mipomersen: a safe and effective antisense therapy adjunct to statins in patients with hypercholesterolemia. AB - Mipomersen is an antisense oligonucleotide inhibitor of apolipoprotein (apo) B 100 currently in phase 3 of development for the treatment of hyperlipidemia in patients with a high risk for cardiovascular disease. The drug acts by inhibiting the production of apoB-100, which is the structural core for all atherogenic lipids, including low-density lipoprotein cholesterol (LDL-C). The agent has been shown to produce significant reductions in LDL-C from baseline values compared with placebos. Clinical trials have demonstrated that mipomersen reduces LDL-C up to 44% in patients with familial hypercholesterolemia and patients with significantly elevated LDL despite taking maximum doses of statins. Unlike other medications that target apoB-100, such as microsomal triglyceride transfer proteins, mipomersen does not cause hepatic steatosis or intestinal steatosis and does not affect dietary fat absorption. Adverse side effects encountered with mipomersen include flu-like symptoms, injection site reactions, and elevated liver transaminases. If future studies continue to show such promising results, mipomersen would likely be a viable additional lipid-lowering therapy for patients who are at high cardiovascular risk, intolerant to statins, and/or not at target lipid levels despite maximum doses of statin therapy. Clinical outcome studies looking at cardiovascular disease end points still need to be done. PMID- 22293858 TI - Three-dimensional Echocardiography in Valvular Heart Disease. AB - Recent technologic advances in 3-dimensional (3D) echocardiography, using parallel processing to scan a pyramidal volume, have allowed for a superior ability to describe valvular anatomy using both transthoracic and transesophageal echocardiography. Although still in evolution and at an early phase of adaptation with respect to its clinical application, 3D echocardiography has emerged as an important clinical tool in the assessment of valvular heart disease. Three dimensional echocardiography provides unique perspectives of valvular structures by presenting "en face" views of valvular structures, allowing for a better understanding of the topographical aspects of pathology, and a refined definition of the spatial relationships of intracardiac structures. Three-dimensional echocardiography makes available indices not described by 2D echocardiography and has been demonstrated to be superior to 2D echocardiography in a variety of valvular disease scenarios. The information gained from 3D echocardiography has especially made an impact in guiding clinical decisions in the evaluation of mitral valve (MV) disease. The decision of early surgery in degenerative MV disease is based on the suitability of repair, and the suitability of repair is generally based on echocardiography. The superior understanding of MV anatomy afforded by 3D echocardiography has been shown to be quite valuable in this setting. This review will describe the contemporary use of 3D echocardiography in the assessment of valvular heart disease, including MV, aortic, tricuspid, and prosthetic valve abnormalities. This article illustrates how 3D echocardiography can complement current echocardiography techniques in the management of valvular heart disease. PMID- 22293859 TI - Cardiovascular antioxidant therapy: a review of supplements, pharmacotherapies, and mechanisms. AB - Oxidant stress plays an important role in the pathogenesis of atherosclerosis. In the late 1980s, biological studies demonstrated that oxygen-free radicals oxidize low-density lipoprotein-cholesterol, resulting in the creation of foam cells and inciting the cascade of biological events that ultimately result in the formation of atherosclerosis. In vitro studies showed the ability of antioxidant vitamins to scavenge free radicals and block the oxidation of low-density lipoprotein. This data was supported in vivo by early observational studies suggesting the benefit of antioxidants, particularly vitamin E, in the prevention of coronary artery disease. On the basis of these studies, the use of antioxidant supplements by the general population increased substantially and became a multibillion dollar industry. Despite strong biological evidence and promising observational data, more rigorous scientific evaluation did not support a causational relationship between vitamin supplements and lowering coronary artery disease risk. Several prospective, double-blind, placebo-controlled trials showed no benefit and possibly harmful effects. Therapies such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and statins, which are known to have benefit in preventing and treating atherosclerosis by reducing blood pressure and cholesterol, also have a "pleiotropic" effect in reducing the formation of reactive oxygen species (ROS). Advances in molecular biology and the study of ROS led to a better understanding of the mechanisms that govern their production and role in atherogenesis. This progress identified unforeseen pathways by which these drugs favorably alter the balance in ROS production, and have raised possibilities for future targeted therapies in the prevention of atherosclerosis. PMID- 22293861 TI - Clopidogrel and genetic testing: is it necessary for everyone? AB - Clopidogrel is a widely used antiplatelet agent to treat and prevent a variety of atherothrombotic diseases. More than a decade after its initial Food and Drug Administration approval, studies have emerged raising concerns regarding its possible reduced efficacy in patients who have impaired conversion of clopidogrel to its active metabolite (ie, poor metabolizers). Research has implicated genetic variations in the CYP2C19 isozyme as at least partly responsible for the variable antiplatelet response seen with clopidogrel. Studies have shown that patients possessing genetic variants of the CYP2C19 isozyme may be at increased risk of adverse cardiovascular events due to impaired clopidogrel efficacy, although this has not been definitively demonstrated. The Food and Drug Administration has issued a boxed warning regarding this concern. However, specific recommendations on genetic testing and alternative therapeutic strategies are not currently available. Genetic testing is commercially available to test patients for variability in the CYP2C19 isozyme, but altering antiplatelet therapy based on the results of this testing has not been adequately studied, and it is therefore not clear how to adjust therapy based on the results of this genetic testing. In addition, there are many other factors that may contribute to the variability in antiplatelet effect seen with clopidogrel besides CYP2C19 genetic polymorphisms. Ongoing trials dealing with adjusting antiplatelet therapy based on genetic testing will hopefully provide more useful information on how to appropriately integrate pharmacogenomics with the care of patients with atherothrombotic disease. PMID- 22293862 TI - Synthesis of quinolines via Friedlander reaction catalyzed by CuBTC metal-organic framework. AB - Friedlander condensation between 2-aminoaryl ketones and different carbonyl compounds, catalyzed by CuBTC was investigated by a combination of various experimental techniques and by density functional theory based modelling. CuBTC exhibiting hard Lewis acid character showed highly improved catalytic activity when compared with other molecular sieves showing high concentraion of Lewis acid sites, e.g. in BEA and (Al)SBA-15. Polysubstituted quinolines were synthesized via a Friedlander reaction catalyzed by CuBTC under the solvent-free conditions. High concentration of active sites in CuBTC together with the concerted effect of a pair of adjacent Cu(2+) coordinatively unsaturated active sites are behind a very high quinoline yield reached within a short reaction time. Results reported here make CuBTC a promising catalyst for other Lewis acid-promoted condensations, including those leading to biologically active compounds with a particular relevance for the pharmaceutical industry. The mechanism of a catalyzed Friedlander reaction investigated computationally is also reported. PMID- 22293863 TI - MAPK inhibitors and siRNAs differentially affect cell death and ROS levels in arsenic trioxide-treated human pulmonary fibroblast cells. AB - Arsenic trioxide (ATO; As2O3) induces cell death in various types of cancer cells including lung cancer via increasing reactive oxygen species (ROS) and regulating mitogen-activated protein kinase (MAPK) signaling cascades. However, little is known about the relationship between ATO and MAPK signaling in normal lung cells. Here, we investigated the effects of MAPK inhibitors and siRNAs on ATO-treated human pulmonary fibroblast (HPF) cells in relation to cell growth, cell death, ROS and glutathione (GSH) levels. ATO induced cell growth inhibition and death in HPF cells and it increased ROS levels including O2*- and GSH depleted cell number. None of the MAPK (MEK, JNK and p38) inhibitors affected cell growth inhibition and cell death by ATO. The MEK inhibitor decreased O2*- levels in ATO treated HPF cells whereas JNK and p38 inhibitors generally increased ROS levels including O2*- in these cells. None of these inhibitors altered the ATO-induced GSH depletion. Moreover, ERK siRNA did not change HPF cell growth and death by ATO whereas JNK and p38 siRNAs enhanced cell growth inhibition and death. In addition, JNK and p38 siRNAs increased ROS levels and GSH depletion in ATO treated HPF cells. In conclusion, MAPK inhibitors changed ROS levels in ATO treated HPF cells, but did not affect cell growth inhibition and death. siRNAs targeting JNK and p38 showing an increase in ROS levels and GSH depletion in ATO treated HPF cells augmented cell growth inhibition and death. PMID- 22293860 TI - Chagas heart disease: report on recent developments. AB - Chagas disease, caused by the parasite Trypanosoma cruzi, is an important cause of cardiac disease in endemic areas of Latin America. It is now being diagnosed in nonendemic areas because of immigration. Typical cardiac manifestations of Chagas disease include dilated cardiomyopathy, congestive heart failure, arrhythmias, cardioembolism, and stroke. Clinical and laboratory-based research to define the pathology resulting from T. cruzi infection has shed light on many of the cellular and molecular mechanisms leading to these manifestations. Antiparasitic treatment may not be appropriate for patients with advanced cardiac disease. Clinical management of Chagas heart disease is similar to that used for cardiomyopathies caused by other processes. Cardiac transplantation has been successfully performed in a small number of patients with Chagas heart disease. PMID- 22293864 TI - The microbial cell factory. AB - Microorganisms have been used for decades as sources of antibiotics, vitamins and enzymes and for the production of fermented foods and chemicals. In the 21st century microorganisms will play a vital role in addressing some of the problems faced by mankind. In this article three of the current applications in which microbes have a significant role to play are highlighted: the discovery of new antibiotics, manufacture of biofuels and bioplastics, and production of fine chemicals via biotransformation. PMID- 22293865 TI - All Chinese to me. PMID- 22293866 TI - Daily walking intensity as a predictor of quality of life in patients with chronic obstructive pulmonary disease. AB - PURPOSE: This study aimed to assess independent predictors of quality of life (QOL) in patients with chronic obstructive pulmonary disease, in particular, to evaluate the relationship between QOL and functional exercise capacity measured with an activity monitor. METHODS: Functional exercise capacity was measured with an accelerometer-based walking intensity. QOL was assessed by Short Form-36 and Saint Georges Respiratory Questionnaire. Stepwise multivariate regression analyses were used to identify significant independent predictors of health related QOL. RESULTS: Daily walking intensity (fast walk) was the only significant independent predictor of the Short Form-36 domains "physical function" (P = 0.002) and "role physical" (P = 0.034). Age and depression were significant independent predictors of the domain "social functioning" (P = 0.035 and P = 0.002, respectively). Age and fast walk were significant independent predictors of the domain "mental health" (P = 0.006 and P = 0.017, respectively). Percent predicted forced expiratory volume in 1 s and fast walk were both significant independent predictors of the domains "general health" (P = 0.04 and P = 0.02, respectively) and "physical component score" (P = 0.038 and P = 0.017, respectively). In terms of the Saint Georges Respiratory Questionnaire, fast walk was a significant independent predictor of "activity score" (P = 0.001), "impact score" (P = 0.022), and "total score" (P = 0.01). CONCLUSIONS: QOL is an important aspect to be integrated into long-term disease management and the assessment of daily walking intensity using accelerometry can provide additional information about the patient's functional status and well-being during a certain period. PMID- 22293867 TI - Incidental gastric signet-ring cell carcinoma metastasis to the skin in basal cell carcinoma. PMID- 22293868 TI - Virus infection of the heart--unmet therapeutic needs. AB - For over 50 years, viral infection has been recognized as an important trigger of acute myocarditis, inflammatory dilated cardiomyopathy (DCM) and congestive heart failure. Nevertheless, viral heart disease remains challenging to diagnose and treat. Improved diagnostic methods for myocarditis have led to a better understanding of its pathophysiology. The recognition of virus-mediated damage, inflammation and autoimmune dysregulation in these patients highlights the importance of differentiating between virus-positive and virus-negative inflammatory DCM. These insights have led to the development of novel treatment strategies, including intravenous immunoglobulin and interferon therapy for virus positive patients. This article will focus on the pathogenesis of viral myocarditis, especially parvovirus B19-induced, its progression to inflammatory DCM and future treatment strategies. PMID- 22293869 TI - Determination of PKC isoform-specific protein expression in pulmonary arteries of rats with chronic hypoxia-induced pulmonary hypertension. AB - BACKGROUND: Evidence indicates that protein kinase C (PKC) plays a pivotal role in hypoxia-induced pulmonary hypertension (PH), but PKC isoform-specific protein expression in pulmonary arteries and their involvement in hypoxia-induced PH are unclear. MATERIAL/METHODS: Male SD rats (200-250 g) were exposed to normobaric hypoxia (10% oxygen) for 1, 3, 7, 14 and 21 d (days) to induce PH. PKC isoform specific membrane translocation and protein expression in pulmonary arteries were determined by using Western blot and immunostaining. RESULTS: We found that only 6 isoforms of conventional PKC (cPKC) alpha, betaI and betaII, and novel PKC (nPKC) delta, epsilon and eta were detected in pulmonary arteries of rats by Western blot. Hypoxic exposure (1-21 d) could induce rat PH with right ventricle (RV) hypertrophy and vascular remodeling. The cPKCbetaII membrane translocation at 3-7 d and protein levels of cPKCalpha at 3-14 d, betaI and betaII at 1-21 d decreased, while the nPKCdelta membrane translocation at 3-21 d and protein levels at 3-14 d after hypoxic exposure in pulmonary arteries increased significantly when compared with that of the normoxia control group (p<0.05 vs. 0 d, n=6 per group). In addition, the down-regulation of cPKCalpha,betaI and betaII, and up-regulation of nPKCdelta protein expressions at 14 d after hypoxia were further confirmed by immunostaining. CONCLUSIONS: This study is the first systematic analysis of PKC isoform-specific membrane translocation and protein expression in pulmonary arteries, suggesting that the changes in membrane translocation and protein expression of cPKCalpha, betaI, betaII and nPKCdelta are involved in the development of hypoxia-induced rat PH. PMID- 22293870 TI - Changes in chemiluminescence of whole blood of COPD patients treated with Hypoxen and effects of C60 fullerenes on blood chemiluminescence. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease associated with reactive oxygen species (ROS) production. The aim of this study was to evaluate the effect of Hypoxen treatment and the effect of HyFnC60 on ROS production in patients' blood. MATERIAL/METHODS: ROS production in blood was estimated using chemiluminescence (CL) measurement with CL-amplifiers: luminol (LM), LM + zymosan (ZM) or lucigenin (LC) in the presence or absence of hydrated fullerenes (HyFnC60) added to blood in low concentrations. RESULTS: In all the patients with COPD in remission phase with Hypoxen prescription, the LM dependent CL (LM-CL) with ZM and LC-enhanced CL (LC-CL) decreased after the treatment. Parameters of CL and effects of HyFnC60 upon them depended on blood state. Addition of HyFnC60 to blood decreased data scattering and helped to improve discrimination between different groups of patients. Using the discriminator analysis, we found the most important time-points in the kinetic curves of CL for classification of patients into groups (eg, COPD patients before and after treatment with Hypoxen; patients' blood with different sensitivity to HyFnC60 concentration). CONCLUSIONS: Monitoring of CL of non-diluted whole blood in COPD patients can be used for the estimation of the Hypoxen efficiency in complex therapy. Addition of HyFnC60 to blood increases sensitivity of the method. PMID- 22293871 TI - Lack of association of conjunctival MALT lymphoma with Chlamydiae or Helicobacter pylori in a cohort of Chinese patients. AB - BACKGROUND: This study was conducted to detect microbial pathogens in conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma specimens in an attempt to determine possible associations between conjunctival MALT lymphoma and microbial infections. MATERIAL/METHODS: Using PCR technique, freshly obtained tumor specimens from 16 cases of conjunctival MALT lymphoma, as confirmed by postoperative pathology, were analyzed for DNA of Chlamydia psittaci (C. psittaci), Chlamydia trachomatis (C. trachomatis), Chlamydia pneumoniae (C. pneumoniae) and Helicobacter pylori (H. pylori). Synthetic C. psittaci, C. trachomatis, C. pneumoniae and H. pylori DNA were used as positive control, and blank plasmid DNA as negative control. RESULTS: Electrophoresis showed that no bands corresponding to the positive control were observed in the specimens, indicating that no DNA of the 4 microorganisms was detected in the specimens of the 16 cases of conjunctival MALT lymphoma. CONCLUSIONS: The PCR technique was able to detect the positive control quickly and accurately, but the results of PCR in analyzing the 16 specimens were negative, indicating that there is no association between conjunctival MALT lymphoma and the 4 microorganisms in Chinese patients. PMID- 22293872 TI - Postcardiac injury syndrome (part II). AB - A 58-year-old man had undergone 2-vessel off-pump coronary artery bypass surgery (OPCAB), 1 month before he was admitted into the hospital with cardiac tamponade due to pericarditis. Postcardiac injury syndrome (PCIS) was diagnosed. In spite of receiving anti-inflammatory treatment, the patient developed relapsing PCIS. PMID- 22293873 TI - The influence of heparin resistance on postoperative complications in patients undergoing coronary surgery. AB - BACKGROUND: Heparin resistance is relatively frequent in patients undergoing coronary surgery. We aimed to assess the impact of heparin resistance on the outcome of patients undergoing coronary surgery with cardiopulmonary bypass (CABG). Three definitions of heparin resistance were adopted. MATERIAL/METHODS: We performed a retrospective review of 756 consecutive patients undergoing isolated CABG. All anaesthesia records were reviewed manually. Heparin resistance was recognized if: ACT was less than 400 seconds after 300 U/kg heparin (local criteria), ACT was less than 480 seconds after 400 U/kg or more heparin (stringent criteria), or if heparin sensitivity index was lower than 1.3. Postoperative assessment included perioperative morbidity and mortality. A multiple logistic regression model was used to investigate the influence of all demographic, preoperative and surgical variables, as well as heparin resistance (variably defined) on hospital mortality and postoperative complications. RESULTS: Heparin sensitivity index, local criteria and stringent criteria identified 64.8%, 12.0% and 4.3% heparin resistant patients, respectively. Heparin-resistant patients more frequently had preoperative heparin administration, unstable course of coronary artery disease, and higher coronary symptoms scoring. Severe form of heparin resistance (expressed by the ACT less than 480 seconds after 400 U/kg heparin) was an independent predictor of death (OR 4.92; CI 1.11-21.89). CONCLUSIONS: Mild forms of heparin resistance are relatively frequent and are not associated with increased morbidity and mortality. The isolation of severe heparin resistance as an independent predictor of death in our large cohort of coronary patients suggests that this phenomenon should be given more attention in future studies. PMID- 22293874 TI - Head and neck cancer: value of perfusion CT in depicting primary tumor spread. AB - BACKGROUND: The aim of this study was to assess head and neck squamous cell cancer and surrounding tissue in computed tomography contrast enhanced and perfusion studies, and to examine the role of perfusion imaging in depiction of tissue infiltration. MATERIAL/METHODS: We prospectively evaluated 43 primary malignant head and neck tumors, using standard CT followed by perfusion. Blood flow, blood volume, mean transit time, and permeability values were obtained using regions of interest (ROIs) over lesions and surrounding tissue. Results were compared with histological analysis of resected tissue. Sensitivity, specificity, accuracy, positive and negative predictive values were calculated for both methods. RESULTS: We found significant differences between infiltrated and non-infiltrated tissue, especially with regard to muscles. In case of bone and salivary gland infiltration, change in perfusion parameters did not allow proper diagnosis. CONCLUSIONS: CTP shows promise in depicting malignant infiltration. The combined use of CECT plus CTP results in correct staging of the majority of head and neck tumors. PMID- 22293875 TI - Self-esteem and styles of coping with stress versus strategies of planning in people with psychopathic personality disorders. AB - BACKGROUND: Psychopathy is a notion that has been difficult to define. The operational definition of psychopathy by Hare is one of the most commonly used in psychology and it is usually identified with the scale used to measure this type of personality, which is the Psychopathy Checklist - Revision (PCL-R). PCL-R is composed of two factors: Factor 1 describes a constellation of psychopathic traits considered by many clinicians to be basic for this type of personality, and Factor 2 describes types of behaviour indicating impulsiveness, lack of stability and antisocial lifestyle. The aim of the research was to verify a hypothesis that people with psychopathic personality disorders are characterised by high self-esteem, unconstructive strategies of planning actions and non adaptive styles of coping with stress. MATERIAL/METHODS: The group of participants included 30 people at the age of 22-36 convicted with a legally binding sentence. Methods were: 1. The Psychopathy Checklist-Revision (PCL-R); 2. Antisocial Personality Questionnaire (APQ); 3. Coping Inventory for Stressful Situations (CISS); 4. Generalised Self-Efficacy Scale (GSES). RESULTS: The participants were diagnosed as psychopaths (PCL-R), and more specifically - as primary psychopaths (APQ). They revealed a grandiose sense of self-worth, increased self-control, impulsive style of functioning, perceived high self efficacy (which might be considered as a defence mechanism). Psychopaths prefer a coping style focused on emotions and avoidance. CONCLUSIONS: The hypothesis was confirmed, that people with psychopathic personality disorders are characterised by high self-esteem, unconstructive strategies of planning actions and non adaptive styles of coping with stress. PMID- 22293876 TI - Inhibitory effects of intravenous lansoprazole 30 mg and pantoprazole 40 mg twice daily on intragastric acidity in healthy Chinese volunteers: a randomized, open labeled, two-way crossover study. AB - BACKGROUND: Until now there has been no study that directly compares the effect of lansoprazole and pantoprazole administered intravenously on intragastric acidity. The aim of this study is to compare the effect of lansoprazole (30 mg) and pantoprazole (40 mg) administered intravenously on gastric acidity. MATERIAL/METHODS: Helicobacter pylori-negative healthy volunteers were recruited in this open-label, randomized, two-way crossover, single centre study. Lansoprazole at 30 mg or pantoprazole at 40 mg was intravenously administered twice daily for 5 consecutive days with at least a 14-day washout interval. Twenty-four-hour intragastric pH was continuously monitored on days 1 and 5 of each dosing period. RESULTS: Twenty-five volunteers completed the 2 dosing periods. The mean intragastric pH values were higher in subjects treated with lansoprazole than those with pantoprazole on both day 1 (6.41 +/- 0.14 vs. 5.49 +/- 0.13, P=0.0003) and day 5 (7.09 +/- 0.07 vs. 6.64 +/- 0.07, P=0.0002). Significantly higher percentages of time with intragastric pH >4 and pH >6 were found in the subjects treated with lansoprazole than those with pantoprazole on day 1 (pH >4, 87.12 +/- 4.55% vs. 62.28 +/- 4.15%, P=0.0012; pH >6, 62.12 +/- 4.12% vs. 47.25 +/- 3.76%, P=0.0216) and pH >6 on day 5 (76.79 +/- 3.77% vs. 58.20 +/- 3.77%, P=0.0025). CONCLUSIONS: Intravenous lansoprazole produces a longer and more potent inhibitory effect on intragastric acidity than does intravenous pantoprazole. PMID- 22293877 TI - Indocyanine green angiography in chronic central serous chorioretinopathy. AB - BACKGROUND: Central serous chorioretinopathy (CSC) is a condition that originates from alterations of the choroidal circulation. The aim of this paper was to evaluate the use of indocyanine green angiography (ICGA) in patients with chronic CSC. MATERIAL/METHODS: The analysis included 17 patients (34 eyes) with chronic CSC in at least 1 eye. The eye examination included: distance and near visual acuity, biomicroscopy, applanation tonometry, fundus examination, colored and red free fundus photography, evaluation of autofluorescence, optical coherence tomography, and fluorescein and indocyanine green angiography. RESULTS: In 34 eyes (100%) involved in the ICGA study the results revealed zones of transient increased choroidal vessels permeability. In 18 eyes (52.9%) choroidal changes were accompanied by a focal serous pigment epithelial detachment. In 4 eyes (11.8%) of 3 patients' the ICGA examination confirmed the presence of occult choroidal neovascularization (CNV). In the patient with bilateral diffuse retinal pigment epitheliopathy, CNV was present in 1 eye, in the patient with unilateral chronic CSC it was also present in 1 eye, and in the third patient with bilateral chronic CSC it was detected in both eyes. CONCLUSIONS: ICGA is a very useful examination that enables ophthalmologists to visualize choroidal changes due to chronic CSC, as well as to diagnose occult CNV in chronic CSC. PMID- 22293878 TI - Periodontal microcirculation in diabetics: an in vivo non-invasive analysis by means of videocapillaroscopy. AB - BACKGROUND: Diabetes mellitus is today considered a society-wide disease of a chronic/degenerative nature. Among the secondary effects of diabetes, the one that interests the dental surgeon most is diabetic parodontopathy. The aim of this study was to underline and objectify microcirculatory variations at a periodontal mucous level in type 2 diabetics. MATERIAL/METHODS: The study enrolled 80 subjects: 40 subjects with a diagnosis of diabetes mellitus type II (18 males and 22 females, between 44 and 85 years of age); and 40 healthy subjects (17 males and 23 females, between 44 and 78 years of age). All the subjects, both diabetic and healthy, were submitted to a videocapillaroscopic examination of the mucosa of the oral cavity. RESULTS: The measurements concerning the density (expressed in the number of loops/mm2) of the capillary loops presented differences between the healthy subjects and the diabetic subjects. The average periodontal capillary density (DC-P) was clearly superior in diabetic subjects (35.62 +/- 10.40 n degrees loop/mm2) compared to healthy subjects (17.55 +/- 3.88 n degrees loop/mm2). The statistical analysis was performed by means of the Mann Whitney test. The value of P (p=0.000000986), well below the level of significance, demonstrates the high significance of the results obtained. CONCLUSIONS: The increase in capillary density could suggest the presence of active inflammatory phenomena or, more probably, a tendency to a greater susceptibility to inflammatory phenomena. Ultimately, this study shows that there is some peripheral damage to microcirculation at the masticatory mucous level in diabetic subjects and that such alterations can be instrumentally objectified and quantified through the videocapillaroscopic method. PMID- 22293879 TI - Sex-specific association of anthropometric measures of body composition with arterial stiffness in a healthy population. AB - BACKGROUND: Anthropometric measures of body composition and arterial stiffness are commonly used as indicators of cardiovascular risk. Little is known, however, about the association of the anthropometric measures with arterial stiffness, especially in a healthy, generally non-obese population. MATERIAL/METHODS: In a sample of 352 healthy subjects (200 premenopausal women), 3 arterial stiffness indices were analyzed (pulse wave velocity, augmentation index and central systolic blood pressure) in relation to 5 anthropometric measures of body composition (body mass index - BMI, body fat percentage by skinfold measurements %BF, waist circumference - WC, waist-hip ratio - WHpR, and waist-height ratio - WHtR). Data were analyzed using correlation and regression analyses, with adjustment for the following confounders: age, blood pressures, height, heart rate, blood lipids and smoking. RESULTS: Most correlations between anthropometric measures and arterial stiffness indices were significant and positive in both sex groups (r=0.14-0.40, P<0.05). After adjustment for confounding effects, BMI, WC and WHtR remained significant (but inverse) predictors of arterial stiffness (beta from -0.06 to -0.16; P<0.05) in the females, while in the males BMI was the only measure inversely predicting arterial stiffness (beta from -0.09 to -0.13; P<0.05). CONCLUSIONS: Measures of body composition are weak and inverse predictors of arterial stiffness and their influence is sex-dependent. BMI, WC and WHtR were key predictors of arterial stiffness in the females, while BMI was the principal predictor in the males. The associations of anthropometric measures with arterial stiffness are strongly and differently confounded by various factors that have to be taken into account when explaining results of similar studies. PMID- 22293880 TI - Persistence of initial oral antidiabetic treatment in patients with type 2 diabetes mellitus. AB - BACKGROUND: Adequate persistence of oral antidiabetic treatment is highly important to achieve proper glycemic control in patients with type 2 diabetes. The aim of this study was to evaluate the persistence of initial treatment with metformin and/or sulphonylureas in patients with type 2 diabetes. MATERIAL/METHODS: The study was performed among diabetic patients (n=256,384) who were with newly prescribed oral antidiabetic drugs (metformin and/or sulphonylureas) between 2007 and 2009. For making comparison, patients with newly prescribed statin or clopidogrel therapy (with and without percutaneous coronary intervention) were investigated. The database of the Hungarian National Health Insurance Fund Administration was used. RESULTS: The 1-year persistence of initial treatment with metformin, sulphonylureas or metformin/sulphonylurea combination was 47.7%, 45.4% and 55.8%, respectively, which was significantly better than the persistence of statin therapy (26.3%) but worse than that of clopidogrel therapy in patients undergoing coronary intervention (73.2%). Within the sulphonylurea group there was a tendency of better persistence of treatment with the "modified-release" tablets at 12 months compared to the conventional sulphonylureas (47.8 vs. 42.2%). The persistence of therapy using metformin 1000 mg - 60 tablets was significantly better (60.4%) at 12 months than that of other forms of metformin therapy with lower doses and smaller boxes (with fewer tablets) analyzed together (47.7%). CONCLUSIONS: The persistence of initial treatment with metformin and/or sulphonylureas is far from optimal. Better diabetic care and continuous patient education should be encouraged to achieve higher persistence of oral antidiabetic treatment in patients with type 2 diabetes. PMID- 22293881 TI - Relation of hs-CRP and BNP levels with the atrial spontaneous echo contrast and thrombi in permanent atrial fibrillation patients with different etiologies. AB - BACKGROUND: Thromboembolic risk in permanent atrial fibrillation (AF) is strongly associated with the underlying etiology, and inflammatory parameters may contribute. The present study aimed to investigate the relationship of hs-CRP and BNP levels with left and right atrial appendage (LAA and RAA) function, presence of spontaneous echo contrast (SEC) and thrombus. MATERIAL/METHODS: Eighty-four permanent AF patients with different etiologies (20 mitral stenosis, 44 hypertension and 20 hyperthyroidism) and 23 patients with sinus rhythm were included. LAA and RAA flow velocities were measured by pulsed-wave Doppler and wall motion velocities with tissue Doppler imaging (TDI) in transesophageal echocardiography. RESULTS: Hs-CRP and BNP levels significantly differed among the 3 AF groups: levels were highest in mitral stenosis patients (8.6 +/- 5.3 mg/L and 98.0 +/- 125.7 pg/mL, respectively), the lowest hs-CRP was in hyperthyroidism patients (4.3 +/- 3.8 mg/L), and the lowest BNP was in hypertensive patients (64.8 +/- 44.3 pg/mL). There were also significant differences between the AF group and controls regarding hs-CRP and BNP levels. In the correlation analysis, BNP level was not significantly correlated with LAA and RAA functions, whereas hs CRP level was significantly correlated with some LAA and RAA functions. On the other hand, hs-CRP level was significantly related to the presence of mild moderate SEC and thrombi, mainly in mitral stenosis patients. Moreover, hs-CRP was the most important determinant of RAA thrombus formation, followed by RAA ejection fraction. In contrast, no positive or negative correlation was found between BNP levels and RAA and LAA thrombi. CONCLUSIONS: Higher hs-CRP levels in AF patients may be a predictor for the presence of SEC and thrombi in the atria. PMID- 22293882 TI - Thermal ablation of unresectable liver tumors: factors associated with partial ablation and the impact on long-term survival. AB - BACKGROUND: Thermal ablation procedures, including radiofrequency ablation (RFA) or laser-induced interstitial thermotherapy (LITT), are now well established in the treatment of malignant unresectable hepatic tumors. But the impact of partial ablation (PA) on long-term survival following computed tomography (CT)-guided radiofrequency ablation and laser- induced interstitial thermotherapy of unresectable malignant liver lesions and the associated risk factors of PA remain partially unknown. MATERIAL/METHODS: This study included 254 liver tumors in 91 consecutive patients (66 men and 25 women; age 60.9 +/- 10.4 years; mean tumor size 25 +/- 14 mm [range 5-70 mm]) who underwent thermal ablation (RFA or LITT) between January 2000 and December 2007. Mean follow-up period was 21.1 month (range 1-69 months). Survival rate and local progression-free survival (PFS) were calculated for patients with complete ablation (CA) vs. patients with partial ablation (PA) to assess the impact on long-term survival. RESULTS: Median survival after CA was 47 months compared to 25 months after PA (P=0.04). The corresponding 5-year survival rates were 44% vs. 20%. Median PFS for CA was 11 months compared to 7 months for PA (P=0.118). The sole statistically significant risk factor for PA was tumor size (>30 mm; P=0.0003). Sustained complete ablation was achieved in 71% of lesions <= 30 mm vs. 47% of lesions >30 mm. CONCLUSIONS: We conclude that achievement of complete ablation is a highly important predictor of long-term survival and that tumor size is by far the most important predictor of the likelihood of achieving complete ablation. PMID- 22293883 TI - Dentigenous infectious foci - a risk factor of infective endocarditis. AB - BACKGROUND: Dentigenous, infectious foci are frequently associated with the development of various diseases. The role of such foci in the evolution of endocarditis still remains unclear. This article presents the concluding results of an interdisciplinary study verifying the influence of dentigenous, infectious foci on the development of infective endocarditis. MATERIAL/METHODS: The study subjects were 60 adult patients with history of infective endocarditis and coexistent acquired heart disease, along with the presence at least 2 odontogenic infectious foci (ie, 2 or more teeth with gangrenous pulp and periodontitis). The group had earlier been qualified for the procedure of heart valve replacement. Swabs of removed heart valve tissue with inflammatory lesions and blood were then examined microbiologically. Swabs of root canals and their periapical areas, of periodontal pockets, and of heart valves were also collected. RESULTS: Microbial flora, cultured from intradental foci, blood and heart valves, fully corresponded in 14 patients. This was accompanied in almost all cases by more advanced periodontitis (2nd degree, Scandinavian classification), irrespective of the bacterial co-occurrence mentioned. In the remaining patients, such consistency was not found. CONCLUSIONS: Among various dentigenous, infectious foci, the intradental foci appear to constitute a risk factor for infective endocarditis. PMID- 22293884 TI - A case of bilateral persistent sciatic artery with unilateral aneurysm: an 18 year period of graft patency after excision of aneurysm. AB - BACKGROUND: A persistent sciatic artery (PSA) is a rare vascular anomaly with an estimated incidence of 0.02-0.04% and with a high rate of complications such as aneurysm formation, thromboembolism, and ischemia, that may lead to amputation. CASE REPORT: We present a case of a female patient with complete symptomatic ambilateral PSA and with unilateral aneurysm. The aneurysm was excised and the PTFE graft was interposed at the aneurismal sac (femoro-popliteal bypass could not be performed because of the high degree hypoplasia of the superficial femoral artery). The graft endured continuous compression and stretching during regular daily life of the patient. At check-up 18 years after the operation, the Doppler ultrasound showed a patent graft and no new aneurismal dilatation of the sciatic artery. CONCLUSIONS: To our knowledge the follow-up of the presented case is the longest reported so far in the literature. The uneventful course of the patient confirms that classical aneurysmectomy still constitutes one of the treatment options of PSA aneurysm. PMID- 22293885 TI - Mirror, mirror on the wall: hypercalcemia as a consequence of modern cosmetic treatment with liquid silicone. AB - BACKGROUND: Hypercalcemia is a common problem in clinical practice and can be related to endocrine disorders or malignant disease, especially in elderly patients. Although rare, other causes can also be responsible. CASE REPORT: Granulomatous inflammation of the skin and lymph nodes induced by intravenous or injectable silicone is a rare condition of hypercalcemia that is usually not within the scope of differential diagnosis. Here, we report a 72-year-old woman with symptomatic hypercalcemia related to cosmetic treatment of the neck. Topical applied liquid silicone by means of a focal ultrasound device induced extensive granulomatous inflammation of the skin and local lymph nodes, being the underlying cause for hypercalcemia in this case. CONCLUSIONS: In rare cases, symptomatic hypercalcemia can be caused by silicone due to a severe granulomatous tissue reaction. This is the first time that a transdermal silicone treatment has been reported to cause severe granulomatous tissue inflammation. PMID- 22293886 TI - Massive bleeeding from upper gastrointestinal tract as a symptom of rupture of splenic artery aneurysm to stomach. AB - BACKGROUND: Splenic artery aneurysm is the most common aneurysm of visceral vessels. Their rupture usually leads to massive bleeding, being a direct life threat. Splenic artery aneurysms usually rupture into the free peritoneal cavity, and much less frequently into the lumen of the gastrointestinal tract. CASE REPORT: We describe the case of a 38-year-old male patient, who, as a result of chronic pancreatitis, developed a false aneurysm of the splenic artery, which initially caused necrosis of the large intestine and bleeding into its lumen, and subsequently necrosis of the posterior stomach wall with the aneurysm rupture to the stomach lumen with a dramatic course. CONCLUSIONS: The case described confirms that splenic artery aneurysm can be a cause of bleeding to both upper and lower parts of the gastrointestinal tract, and the aneurysm rupture is usually of a dramatic and life-threatening course. PMID- 22293887 TI - Safety of embolic protection device-assisted and unprotected intravascular ultrasound in evaluating carotid artery atherosclerotic lesions. AB - BACKGROUND: Significant atherosclerotic stenosis of internal carotid artery (ICA) origin is common (5-10% at >= 60 years). Intravascular ultrasound (IVUS) enables high-resolution (120 um) plaque imaging, and IVUS-elucidated features of the coronary plaque were recently shown to be associated with its symptomatic rupture/thrombosis risk. Safety of the significant carotid plaque IVUS imaging in a large unselected population is unknown. MATERIAL/METHODS: We prospectively evaluated the safety of embolic protection device (EPD)-assisted vs. unprotected ICA-IVUS in a series of consecutive subjects with >= 50% ICA stenosis referred for carotid artery stenting (CAS), including 104 asymptomatic (aS) and 187 symptomatic (S) subjects (age 47-83 y, 187 men). EPD use was optional for IVUS, but mandatory for CAS. RESULTS: Evaluation was performed of 107 ICAs (36.8%) without EPD and 184 with EPD. Lesions imaged under EPD were overall more severe (peak-systolic velocity 2.97 +/- 0.08 vs. 2.20 +/- 0.08 m/s, end-diastolic velocity 1.0 +/- 0.04 vs. 0.7 +/- 0.03 m/s, stenosis severity of 85.7 +/- 0.5% vs. 77.7 +/- 0.6% by catheter angiography; mean +/- SEM; p<0.01 for all comparisons) and more frequently S (50.0% vs. 34.6%, p=0.01). No ICA perforation or dissection, and no major stroke or death occurred. There was no IVUS-triggered cerebral embolization. In the procedures of (i) unprotected IVUS and no CAS, (ii) unprotected IVUS followed by CAS (filters - 39, flow reversal/blockade - 3), (iii) EPD-protected (filters - 135, flow reversal/blockade - 48) IVUS + CAS, TIA occurred in 1.5% vs. 4.8% vs. 2.7%, respectively, and minor stroke in 0% vs. 2.4% vs. 2.1%, respectively. EPD intolerance (on-filter ICA spasm or flow reversal/blockade intolerance) occurred in 9/225 (4.0%). IVUS increased the procedure duration by 7.27 +/- 0.19 min. CONCLUSIONS: Carotid IVUS is safe and, for the less severe lesions in particular, it may not require mandatory EPD use. High-risk lesions can be safely evaluated with IVUS under flow reversal/blockade. PMID- 22293888 TI - Prevalence of metabolic syndrome in elderly Japanese-Brazilians. AB - BACKGROUND: Prevalence of individuals with a high cardiovascular risk is elevated in elderly populations. Although metabolic syndrome (MS) increases cardiovascular risk, information is scarce on the prevalence of MS in the elderly. In this study we assessed MS prevalence in a population of elderly Japanese-Brazilians using different MS definitions according to waist circumference cutoff values. MATERIAL/METHODS: We studied 339 elderly subjects, 44.8% males, aged between 60 to 88 years (70.1 +/- 6.8). MS was defined according to criteria proposed by the Joint Interim Statement in 2009. As waist circumference cutoff point values remain controversial for Asian and Japanese populations, we employed 3 different cutoffs that are commonly used in Japanese epidemiological studies: 1) >= 90 cm for men and >= 80 cm for women; 2) >= 85 cm for men and >= 90 cm for women; 3) >= 85 cm for men and >= 80 cm for women. RESULTS: MS prevalence ranged from 59.9% to 65.8% according to the different definitions. We observed 90% concordance and no statistical difference (p>0.05) in MS prevalence between the 3 definitions. MS diagnosis according to all 3 cutoff values was found in 55.8% of our population, while in only 34.2% was MS discarded by all cutoffs. The prevalence of altered MS components was as follows: arterial blood pressure 82%, fasting glycemia 65.8%, triglyceride 43.4%, and HDL-C levels 36.9%. CONCLUSIONS: Elderly Japanese Brazilians present high metabolic syndrome prevalence independent of waist circumference cutoff values. Concordance between the 3 definitions is high, suggesting that all 3 cutoff values yield similar metabolic syndrome prevalence values in this population. PMID- 22293889 TI - The temporal relationship between RotaTeq immunization and intussusception adverse events in the Vaccine Adverse Event Reporting System (VAERS). AB - BACKGROUND: In August of 2006, the Advisory Committee on Immunization Practices (ACIP) recommended RotaTeq for routine vaccination of US infants. The hypothesis tested in the present study is that rotavirus vaccines are associated with an increased risk of intussusception adverse events (AEs) characterized by an onset in a biologically plausible a priori identified temporal period post-vaccination (days 3 to 7). MATERIAL/METHODS: The Vaccine Adverse Event Reporting System (VAERS) updated as of December 28, 2010 was analyzed. RESULTS: Following RotaTeq vaccination, a significantly (p<0.001) higher percentage of AEs were classified as serious, permanently disabling, resulted in hospitalizations, or were life threatening among intussusception AEs in comparison to the total AE reports (removing intussusception AE reports) submitted to VAERS. A significantly greater portion of intussusception AEs in comparison to the portion of total AE reports (removing intussusception AE reports) were reported to VAERS in the onset interval from 3 to 7 days post-RotaTeq vaccination than within the onset interval from 1 to 2 days post-RotaTeq vaccination (78.7% vs. 29.1%, risk ratio=2.7, 95% CI=2.4-3.0, p<0.0001). It was assumed in our onset time-trend analyses of the distribution of AEs following Rota-Teq vaccination that the AE's should be equally likely to be reported with an onset time for each day, from 1 to 9 days post-vaccination or, alternatively, should follow similar daily proportions as observed for total AEs reports (removing intussusception AE reports). Results of this onset time-trend analyses of the distribution of intussusception AEs reported to VAERS following Rota-Teq vaccination revealed significant differences (p<0.001) from our expectations. Consistent and similarly remarkable trends were observed for intussusception AE reports associated with RotaShield vaccine. CONCLUSIONS: The present study significantly associates RotaTeq vaccination with intussusception AEs. PMID- 22293890 TI - How well do anthropometric indices correlate with cardiovascular risk factors? A cross-sectional study in Croati. AB - BACKGROUND: Usefulness of anthropometric indices (AI) as predictors of CV risk is unclear and remains controversial. MATERIAL/METHODS: To evaluate the correlation between AI and CV risk factors in the Croatian adult population and to observe possible differences between coastal and inland regions and urban and rural settlements. CRISIC-fm (ISRCTN31857696) is a prospective, randomized cohort study conducted in GP (general practitioner) practices in Croatia. Between May and July 2008, 59 GPs each recruited 55 participants aged >= 40 years, who visited a practice for any reason. Height, weight, waist and hip circumference and blood pressure were measured. Blood samples were analyzed in accredited laboratories. RESULTS: Out of 2467 participants (61.9% women, 38.1% men), 36.3% were obese, with fewer in coastal than inland areas. More obese people were in rural areas. Logistic regression showed BMI was the most important predictor of hypertension, diabetes and dyslipidemia in both regions (except for diabetes in the coastal area), and for urban and rural settlements (except for diabetes in rural areas). WtHR was a significant predictor for hypertension and dyslipidemia in the coastal (but only for hypertension in the inland area), and in urban settlements (in rural only for hypertension). None of the AI showed significant correlation with total CV risk, but WC and BMI did with stroke risk. Receiver operating curve (ROC) analyses showed that WtHR was a better predictor than all other AI for hypertension and dyslipidemia. CONCLUSIONS: Results encourage the use of BMI and WtHR as important tools in predicting CV risk in GP's practice. PMID- 22293891 TI - The application of Levulan-based photodynamic therapy with imiquimod in the treatment of recurrent basal cell carcinoma. AB - BACKGROUND: Common skin tumors like basal- and squamous-cell carcinoma present a serious problem in modern medicine. Exposure to ultraviolet solar radiation is the main cause of these lesions. Since application of Aldara and PDT separately is well documented, we decided to use both methods together. The aim of our study was to evaluate the effectiveness of local photodynamic therapy supplemented with topical application of Aldara in basal-cell carcinoma. MATERIAL/METHODS: Thirty four patients ages 50 to 68 years were enrolled to the trial and underwent PDT treatment. Each case of BCC was histopathologically confirmed. Ten patients were subjected to local Levulan-PDT and placebo (Eucerin as vehicle cream), and 24 patients were subjected to Levulan-PDT and imiquimod. Photodynamic diagnosis (PDD) was used to detect and visualize suspicious foci (including cancer lesions). RESULTS: In the group of patients who were treated using Levulan-PDT and placebo, 6 patients (60%) were totally cured and 4 lesions (40%) significantly decreased in size. In the group of patients treated with Levulan PDT and imiquimod, 18 lesions totally disappeared (75%), 6 lesions significantly diminished, and in 1 patient small foci of previously excised BCC developed again in scar tissue 10 month after the first control examination. CONCLUSIONS: Cure was achieved without any scarring and with very good cosmetic effects. Although this is the preliminary report, the presented modification of PDT seems to be reasonable and promising in treating basal-cell carcinoma. PMID- 22293892 TI - A69S and R38X ARMS2 and Y402H CFH gene polymorphisms as risk factors for neovascular age-related macular degeneration in Poland - a brief report. AB - BACKGROUND: The wet form of age-related macular degeneration (ARMD) is a leading cause of irreversible blindness in Caucasians. Our purpose was to assess influence of gene polymorphisms A69S (rs10490924) and R38X (rs2736911) ARMS2 and Y402 (rs1061170) CFH on wet ARMD risk in a Polish population. MATERIAL/METHODS: 130 unrelated patients (90 with wet ARMD and 40 controls) took part in the study. Dry blood was used for DNA isolation. PCR amplification and gene sequencing were performed. In subjects with R38X and A69S, SNP gene cloning was used to exclude the possible combined variant. RESULTS: Homozygous Y402H and A69S conferred a significance risk of wet ARMD in Poland: Y402H odds ratio (OR) was 5.57 (95% confidence interval: 1.58-19.6), p=0.002; and A69S OR was 7.72 (95% confidence interval: 1.73-34.36), p=0.001. R38X is probably more common in healthy subjects: OR was 0.45 (95% confidence interval: 0.19-1.05), p=0.053. CONCLUSIONS: The etiologic role in ARMD of A69S ARMS2 and Y402H CFH gene variants were confirmed in a Polish population for the first time. R38X variant of ARMS2 seems to be protective from wet ARMD. PMID- 22293893 TI - Effect of filler size and morphology on viscoelastic stability of resin composites under dynamic loading. AB - Effect of variation in filler particle size, morphology and wet conditioning on the viscoelastic stability of resin-composites under dynamic loading was investigated. Eight experimental light cured resin-composites were selected. For each of the eight resin-composites, ten cylindrical specimens (4 * 6 mm), divided into two subgroups (n = 5) were prepared. Group 1 and 2 were loaded dynamically after 1 day of dry storage and 1 week of wet storage, respectively. A cyclic load between 1 and 50 MPa was applied for both groups at a frequency of 0.25 Hz for 30 min to obtain the 'dynamic' creep strain (%). Data was analysed by univariate ANOVA. Unimodal spherical and irregular resin-composites showed a significant influence of particle size and shape on dynamic creep under dry condition, but not for wet conditions. Irregular filler particles in both unimodal and multimodal resin-composites were more resistant to dynamic creep under wet conditions and showed higher stiffness. PMID- 22293894 TI - Inhibition of cell viability by human IFN-beta is mediated by microRNA-431. AB - MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression by cleaving or hindering the translation of target mRNAs. We used microarray-based comparative transcriptome analysis to identify changes in miRNA expression and function between a human cell line, RSa, which is highly sensitive to HuIFN-beta mediated inhibition of cell viability, and its variant, the F-IFr cell line, which is relatively resistant to the cytokine. miR-431 expression was significantly higher in RSa cells compared with F-IFr cells. The addition of HuIFN-beta to RSa cultures reduced cell viability, down-regulated expression of IGF1R and IRS2 (putative miR-431 target genes), and inhibited the PI3K-Akt and MAPK pathways. The survival of F-IFr cells was not reduced by HuIFN-beta, but transient transfection with miR-431 precursors significantly decreased viability and concomitantly down-regulated IGF1R and IRS2 expression. In addition, the MAPK pathway, but not the PI3K-Akt pathway, was suppressed in F-IFr cells. Based on these results, we propose that, in RSa cells, HuIFN-beta-induced miR-431 expression may down-regulate IGF1R and IRS2 expression, and consequently inhibit cell proliferation by suppressing the MAPK pathway. PMID- 22293895 TI - Epstein-Barr virus-positive mucocutaneous ulcers as a manifestation of methotrexate-associated B-cell lymphoproliferative disorders. PMID- 22293896 TI - Theoretical study of photo-physical properties of indolylmaleimide derivatives. AB - Photo-physical properties of bromo-indolylmaleimide (IM-Br), indole-succinimide (IS), and their anions were theoretically investigated compared with the previous theoretical result for indolylmaleimide (IM) [Phys. Chem. Chem. Phys., 2010, 12, 9783]. The energies for the electronic excited states as well as the ground states were computed for these molecules using the multi-reference perturbation calculations based on the second order Rayleigh-Schrodinger perturbation theory (CASPT2) at the cc-pVDZ basis set level. The electron-accepting or electron donating effect caused by bromine-substitution was discussed in the intra molecular charge transfer (ICT) mechanism. The order of natural orbitals of the bromine-substituted monovalent anion with a deprotonated indole NH group (I((-))M Br) was found to be rearranged by the effect of electron-donation, which leads to pseudo-crossing of the potential energy cures of the S(1) and S(2) states. The large stokes shift observed for I((-))M-Br was due to pseudo-crossing. Meanwhile, IM and IM-Br show abnormal deprotonation, which is explained by the charge distribution on the indole and maleimide moieties. Finally, the monovalent anions I((-))M-Br and I((-))M by a deprotonation of the indole NH end and the neutral IS were proposed to be the most feasible candidates corresponding to the experimental spectra in solution. PMID- 22293897 TI - Haemophilic knee arthropathy: long-term outcome after total knee replacement. AB - PURPOSE: The objective of this study was to evaluate the long-term outcome and prosthetic survival of primary total knee arthroplasty in haemophilic patients. It was hypothesized that the infection and revision rate are higher and the outcome inferior when compared with patients without haemophilia. METHODS: Between 1985 and 2004, forty-three consecutive primary total knee replacements were performed in thirty haemophilic patients. These patients' charts were reviewed retrospectively. Twenty-five patients (34 knees) were available for clinical and radiological follow-up. The outcome was assessed using the Knee Society score, WOMAC and Kaplan-Meier survivorship analysis. RESULTS: An haematogenous infection occurred in two patients. In three patients, component revision was needed: two because of an infection and one because of a mechanical failure. After a mean follow-up of 9.6 years (2-20), 94% of the patients rated their result as either excellent or good. At time of follow-up, the Knee Society Score averaged 73.3 points (range, 29-100) and showed a significant gain (p < 0.001) compared to preoperative. Flexion contracture could be reduced significantly (p < 0.001) from 18.1 degrees preoperatively to 8.4 degrees at follow-up, whereas flexion remained unchanged. When infection or any component replacement was set as endpoints, the 10 years prosthetic survival was 90 and 86%, respectively. CONCLUSION: Total knee arthroplasty in haemophilic patients is a reliable treatment that results in pain relief and functional improvement with a low risk of postoperative infection. However, neither the postoperative infection rate nor the functional result does reach the same level as in a population not affected by haemophilia. LEVEL OF EVIDENCE: IV. PMID- 22293898 TI - Functional knee brace use effect on peak vertical ground reaction forces during drop jump landing. AB - PURPOSE: The aim of the study was to investigate the landing strategies used by non-injured athletes while wearing functional knee braces (FKB, BR condition) during a drop jump task compared with non-injured, non-braced (NBR condition) subjects and also to ascertain whether accommodation to a FKB was possible by non injured BR subjects. METHODS: Twenty-three healthy male provincial and national basketball and field hockey athletes (age, 19.4 +/- 3.0 years) were tested. Each subject was provided with a custom-fitted FKB. Five NBR testing sessions were performed over 3 days followed by five BR testing sessions also over 3 days, for a total of 17.5 h of testing per condition. Each subject performed eight trials of the drop jump task during each testing session per condition. Single-leg peak vertical ground reaction forces (PVGRF) and the time to PVGRF were recorded for each NBR and BR trail. RESULTS: The BR group mean PVGRF at landing was significantly lower (1,628 +/- 405 N, 2.1 +/- 0.5 BW versus 1,715 +/- 403 N, 2.2 +/- 0.5 BW, F (1,22) = 6.83, P = 0.01) compared with NBR subjects, respectively. The group mean time to PVGRF was not statistically longer during the BR condition (F (1,22) = 0.967, P = 0.3). Further, an accommodation trend was noted as percent performance difference decreased with continued FKB use. CONCLUSIONS: The significantly lower group mean PVGRF while using a FKB could keep traumatic forces from reaching the ACL until the active neuromuscular restraints are activated to provide protection to the knee joint ligaments. Also, accommodation to FKB is possible after approximately 14.0 h of brace use. The results of this paper will assist clinicians in providing information to their patients regarding a FKB ability to offer protection to an ACL-deficient knee or to address concerns about early muscle fatigue, energy expenditure, heart rate, and decrease in performance level. LEVEL OF EVIDENCE: Prospective study, Level I. PMID- 22293899 TI - Wedge volume and osteotomy surface depend on surgical technique for high tibial osteotomy. AB - PURPOSE: Biplanar open-wedge high tibial osteotomy (HTO) is thought to promote rapid bone healing due to the increased cancellous bone surface compared to other HTO techniques. However, precise data on the bone surface area and wedge volume resulting from both open- and closed-wedge HTO techniques remain unknown. We hypothesized that biplanar rather than uniplanar HTO better reflects the ideal geometrical requirements for bone healing, representing a large cancellous bone surface combined with a small wedge volume. METHODS: Tibial saw bones were assigned to 4 different groups of valgisation high tibial osteotomies: group 1: open-wedge uniplanar HTO; group 2: open-wedge biplanar HTO with ascending frontal cut; group 3: open-wedge biplanar HTO with descending frontal cut (retrotubercule osteotomy technique), and group 4: closed-wedge uniplanar HTO. Bone surface areas of all osteotomy planes were quantified. Wedge volumes were determined using a prism-based algorithm, applying standardized wedge heights of 5, 10, and 15 mm. RESULTS: The open-wedge biplanar osteotomy with a descending frontal cut (group 3) created significantly larger bone surfaces compared to the "classic" biplanar technique with an ascending frontal cut (group 2) and compared to all uniplanar techniques. Bone surfaces after the classic open-wedge technique (group 2) were slightly larger compared to all uniplanar techniques (group 1 and 4). No significant differences of wedge volumes were found between the retrotubercle (group 3) and classic open-wedge techniques (group 2). Wedge volumes were significantly higher in the uniplanar open-wedge technique (group 1) compared to the biplanar open-wedge techniques (group 2 and 3). CONCLUSION: Bone geometry following HTO suggests that the biplanar open-wedge techniques simultaneously create smaller wedge volumes and larger bone surface areas compared to the uniplanar open-wedge techniques. The relatively neglected closed-wedge technique still offers in theory the best healing potential, characterized by an almost absent wedge volume and a large bone-to-bone contact area. Although this idealized geometric view on bony geometry excludes all biologic factors that influence bone healing, the current data suggest a general rule for the applied standard osteotomy techniques and all of their surgical modifications: reducing the amount of slow gap healing and simultaneously increasing the area of faster contact healing may be beneficial for osteotomy healing. Thus, a biplanar rather than a uniplanar osteotomy may be performed for high tibial osteotomy in clinical practice. PMID- 22293900 TI - 3,3'-Diindolylmethane suppresses growth of human esophageal squamous cancer cells by G1 cell cycle arrest. AB - 3,3'-Diindolylmethane (DIM), an active metabolite of indole-3-carbinol, is thought to have antitumor effects in experimental animals and induce apoptosis in various cancer cells. However, the biological functions of DIM in human esophageal cancer cells are unknown. Thus, the purpose of this study was to investigate the cytotoxic effects of DIM in human esophageal squamous cell carcinoma (ESCC) cells to elucidate the molecular mechanism of cell death. Three human ESCC cell lines (TT, TE-8 and TE-12) were used to test the response to DIM. MTT, cell cycle and western blot analyses were conducted. DIM significantly inhibited the proliferation of ESCC cells in a dose- and time-dependent manner. The percentage of G1 phase cells increased 48 h after being treated with DIM. DIM also reduced cyclin D1, cyclin E2, cyclin-dependent kinase (CDK) 4 and CDK 6 activities, and increased p15 and p27 levels. Additionally, DIM diminished pro caspase-9 protein expression levels and induced increased cleaved poly (ADP ribose) polymerase levels. These results indicate that DIM leads to G1 phase cell cycle arrest and induces apoptosis by activating caspase-9 in ESCC cells. PMID- 22293901 TI - A family of 2D and 3D coordination polymers involving a trigonal tritopic linker. AB - Five new coordination polymers, namely, [Zn(2)(H(2)O)(2)(BBC)](NO(3))(DEF)(6) (DUT-40), [Zn(3)(H(2)O)(3)(BBC)(2)] (DUT-41), [(C(2)H(5))(2)NH(2)][Zn(2)(BBC)(TDC)](DEF)(6)(H(2)O)(7) (DUT-42), [Zn(10)(BBC)(5)(BPDC)(2)(H(2)O)(10)](NO(3))(DEF)(28)(H(2)O)(8) (DUT-43), and [Co(2)(BBC)(NO(3))(DEF)(2)(H(2)O)](DEF)(6)(H(2)O) (DUT-44), where BBC--4,4',4'' (benzene-1,3,5-triyl-tris(benzene-4,1-diyl))tribenzoate, TDC--2,5 thiophenedicarboxylate, BPDC--4,4'-biphenyldicarboxylate, DEF--,N diethylformamide, were obtained under solvothermal conditions and structurally characterized. It has been shown that compounds DUT-40, DUT-41 and DUT-44 exhibit 2D layered structures with large hexagonal channels. Utilization of additional angular dicarboxylic TDC linker led to the formation of the DUT-42 compound with the structure consisting of three interpenetrated 3D networks. Using the linear co-linker dicarboxylic BPDC, DUT-43 was obtained which forms a complicated 3D architecture arising from the polycatenation of triple-layered 2D building units and 2D single layer units. The pore accessibility of the synthesized compounds in the liquid phase was proved by the adsorption of dye molecules. PMID- 22293902 TI - Processing numerosity, length and duration in a three-dimensional Stroop-like task: towards a gradient of processing automaticity? AB - The existence of a possible continuum of automaticity for numerosity, length and duration processing was tested with a three-dimensional Stroop-like paradigm. Participants had to compare the numerosity, the length or the duration of two successive linear arrays of sequentially flashed dots in which the three dimensions were manipulated independently to create congruent, incongruent or neutral pairs. The results show that numerosity and length both affected duration processing separately and cumulatively, whereas temporal cues did not influence judgements of numerosity or length. Moreover, length and numerosity influenced each other, with numerical cues having a stronger influence on length processing than the reverse. These findings support the idea that, in sequentially presented stimuli, numerosity, length and duration are processed with different levels of automaticity, with numerosity being processed most, and duration least automatically. PMID- 22293903 TI - Expression of WNT-5a and ROR2 correlates with disease severity in osteosarcoma. AB - Osteosarcoma, a common malignancy primarily affecting children, generally has a poor prognosis. Novel diagnostic, prognostic and therapeutic markers are required to ameliorate the negative outcomes of this disease. We investigated two potential markers, WNT-5a and ROR2, which are hypothesized to dysregulate WNT signaling pathways to promote tumorigenesis in other types of cancer. We investigated WNT-5a and ROR2 expression using immunohistochemistry in 42 osteosarcoma and 12 osteochondroma specimens, and compared the expression of these proteins with one another as well as with clinicopathological parameters. WNT-5a was detected in 34/42 (81.0%) cases and ROR2 was detected in 31/42 (73.8%) cases, significantly higher than in osteochondroma (16.7 and 25.0%, respectively; both P<0.05). Expression of these proteins was positively correlated (r=0.552, P<0.05). Furthermore, expression of WNT-5a and ROR2 was both correlated with Enneking surgical stage and tumor metastasis (P<0.05), but not with patient gender, age or pathological type. Thus, WNT-5a and ROR2 were more highly expressed in more severe disease states, and therefore may play a coordinated role in the occurrence and progression of osteosarcoma. PMID- 22293904 TI - Removal of Pb(II) ions from aqueous solution and industrial effluent using natural biosorbents. AB - PURPOSE: The purpose of the research is to investigate the applicability of the low-cost natural biosorbents for the removal of Pb(II) ions from aqueous solution and effluent from battery industry. METHODS: Six different biosorbents namely rice straw, rice bran, rice husk, coconut shell, neem leaves, and hyacinth roots have been used for the removal of Pb(II) ions from aqueous solution in batch process. All the biosorbents were collected from local area near Kolkata, West Bengal, India. The removal efficiency was determined in batch experiments for each biosorbent. RESULTS: The biosorbents were characterized by SEM, FTIR, surface area, and point of zero charge. The sorption kinetic data was best described by pseudo-second-order model for all the biosorbents except rice husk which followed intraparticle diffusion model. Pb(II) ions adsorption process for rice straw, rice bran, and hyacinth roots were governed predominately by film diffusion, but in the case of rice husk, it was intraparticle diffusion. Film diffusion and intraparticle diffusion were equally responsible for the biosorption process onto coconut shell and neem leaves. The values of mass transfer coefficient indicated that the velocity of the adsorbate transport from the bulk to the solid phase was quite fast for all cases. Maximum monolayer sorption capacities onto the six natural sorbents studied were estimated from the Langmuir sorption model and compared with other natural sorbents used by other researchers. The Elovich model, the calculated values of effective diffusivity, and the sorption energy calculated by using the Dubinin-Radushkevich isotherm were indicated that the sorption process was chemical in nature. The thermodynamic studies indicated that the adsorption processes were endothermic. FTIR studies were carried out to understand the type of functional groups responsible for Pb(II) ions binding process. Regeneration of biosorbents were carried out by desorption studies using HNO3. Battery industry effluents were used for the application study to investigate applicability of the biosorbents. CONCLUSION: The biosorbents can be utilized as low-cost sorbents for the removal of Pb(II) ions from wastewater. PMID- 22293905 TI - Classification of dimension stone wastes. AB - PURPOSE: For countries in which the stone industry is well developed, opposition to quarry and plant waste is gradually increasing. The primary step for waste control and environmental management is to define the problem of concern. In this study, natural building stone wastes were classified for the first time in the literature. METHODS: Following on-site physical observations and research at more than 50 quarries and 20 plants, stone wastes were classified as (1) solid, (2) dust and (3) semi-slurry, slurry and cake. CONCLUSIONS: As a result of this study, the characteristics of wastes, their main environmental threats and the industries in which wastes could be used were defined for each group. PMID- 22293906 TI - Zinc compartmentation in Halimione portulacoides (L.) Aellen and some effects on leaf ultrastructure. AB - INTRODUCTION: The halophyte Halimione portulacoides collected in a polluted area of the river Sado estuary (Portugal) and obtained from hydroponic cultures was used to evaluate the compartmentation of Zn and its preferential binding sites. In parallel, we tried to assess if the minimum available Zn concentration found in marsh soil induces changes at the ultrastructural level. MATERIALS AND METHODS: A sequential extraction method was used to study the Zn compartmentation within the cell. Both dried plant samples and extracts/residues from compartmentation studies were digested by HNO3-HClO4 (4:1) until dryness and analyzed by atomic absorption spectrophotometry. Segments of young leaves, previously exposed to Zn were fixed in glutaraldehyde and osmium tetroxide. Ultrathin sections were stained and examined by transmission electron microscopy at 80 kV. RESULTS AND DISCUSSION: Proteins and carbohydrates of the cell walls constitute preferential binding sites of Zn, containing between 25% and 33% and between 30% and 40% of the total, respectively. Hydroponic plants accumulate Zn in their leaves up to (194 MUg g-1) without visible damage or changes in the protein and chlorophyll concentrations, compared with the controls. Chlorenchyma chloroplasts of Zn-treated plants exhibited an unusual number of starch grains, which can be seen as an alert mechanism. CONCLUSIONS AND PERSPECTIVES: Although so far the levels of Zn in the leaves within the studied area have not reached high values, monitoring them remains a priority. Also, issues related with starch synthesis and organic ligands must be evaluated. The understanding of the predictable behavior of this halophyte is our main goal, and the results here presented can contribute to this achievement. PMID- 22293907 TI - Composition analysis and application of degradation products of whole feathers through a large scale of fermentation. AB - PURPOSE: Feathers are one of the most abundant bioresources. They are discarded as waste in most cases and could cause environmental pollution. On the other hand, keratin constituted by amino acids is the main component of feathers. In this article, we reported on biorefined feathers and integrants and application of degraded products. MATERIALS AND METHODS: The fermentation of whole chicken feathers with Stenotrophomonas maltophilia DHHJ in a scale-up of a 5-L bioreactor was investigated in this article. The fermentation process was controlled at 0.08 MPa pressure, 2.5 L/min airflow, and 300 rpm as 100% oxygen saturation level, 40 degrees C, and pH 7.8. RESULTS: Feathers were almost completely degraded in the tested fermentation reaction with the following conditions: 80 g of whole feathers in 3 L fermentation broth for 72 h, seed age of 16 h, 100 mL inoculation amount, and 50% oxygen saturation level. The degraded products contain 397.1 mg/L soluble protein that has mass weight ranging from 10 to 160 kD, 336.9 mg/L amino acids, and many kinds of metal ions. The fermentation broth was evaluated as leaf fertilizer and found to increase plant growth to 82% or 66% for two- or fourfold dilutions, respectively. In addition, in a hair care assay, the broth showed a hair protective function by increasing weight, flexibility, and strength of the treated hair. CONCLUSIONS: The whole feathers were degraded completely by S. maltophilia DHHJ. The degraded product includes many factors to life, such as peptides, amino acids, and mineral elements. It could be applied as leaf fertilizer and hair care product. PMID- 22293908 TI - Abiotic degradation of chlorinated ethanes and ethenes in water. AB - INTRODUCTION: Chlorinated ethanes and ethenes are among the most frequently detected organic pollutants of water. Their physicochemical properties are such that they can contaminate aquifers for decades. In favourable conditions, they can undergo degradation. In anaerobic conditions, chlorinated solvents can undergo reductive dechlorination. DEGRADATION PATHWAYS: Abiotic dechlorination is usually slower than microbial but abiotic dechlorination is usually complete. In favourable conditions, abiotic reactions bring significant contribution to natural attenuation processes. Abiotic agents that may enhance the reductive dechlorination of chlorinated ethanes and ethenes are zero-valent metals, sulphide minerals or green rusts. OXIDATION: At some sites, permanganate and Fenton's reagent can be used as remediation tool for oxidation of chlorinated ethanes and ethenes. SUMMARY: Nanoscale iron or bimetallic particles, due to high efficiency in degradation of chlorinated ethanes and ethenes, have gained much interest. They allow for rapid degradation of chlorinated ethanes and ethenes in water phase, but they also give benefit of treating dense non-aqueous phase liquid. PMID- 22293909 TI - Reference gene selection for qPCR in mussel, Mytilus edulis, during gametogenesis and exogenous estrogen exposure. AB - PURPOSE: The aim of this study is to develop a normalization method for real-time PCR data by analyzing the most stably expressed control genes in mussel (Mytilus edulis) reproductive tissue. METHODS: To facilitate this, six candidate genes, including several commonly used in the literature, were investigated in mussels at different stages of gametogenesis and following experimental exposure to a model estrogen (17b-estradiol). GeNorm and NormFinder softwares were employed to assess the stability of the reference genes. RESULTS: Our results demonstrate that the most stable reference genes are not the same in mussels at different stages of gametogenesis and in experimentally E2-exposed mussels. Interestingly, HEL (helicase) and ACT (actin) mRNA expression levels were most affected by the stage of gametogenesis and yet, in molluscan studies, ACT is possibly the most frequently used reference gene. CONCLUSIONS: We demonstrate that the experimental results are highly dependent on the reference gene chosen and that statistically significant contrasting differences between sample groups are present or absent depending on the reference gene employed. PMID- 22293910 TI - Thirty-year amendment of horse manure and chemical fertilizer on the availability of micronutrients at the aggregate scale in black soil. AB - PURPOSE: This study evaluates manure and chemical fertilizer effects on micronutrient (Fe, Mn, Cu, and Zn) content and availability in crops. METHODS: Seven treatments were selected, including three conventional fertilization treatments (NP, horse manure (M), and NP plus M (NPM)), three corresponding double rate fertilization (N2P2, M2, and N2P2M2), and a CK. Soil samples were collected and separated into four aggregates by wet-sieving in September 2009. Corn samples were collected and analyzed simultaneously. RESULTS: Treatment N2P2 increased DTPA extractable Fe, Mn, and Cu in soil by 732%, 388%, and 42%, whereas M2 decreased the corresponding values by 26%, 22%, and 10%, respectively, compared to CK. DTPA extractable Zn in soil and Zn in corn grain were higher in the M and M2 treatments than in the other treatments, and DTPA Zn was significantly correlated with soil organic carbon (SOC) in large macroaggregate, microaggregate, and silt + clay fractions. The Mn concentrations in corn stalks and grain were significantly correlated with DTPA extractable Mn in bulk soil and microaggregates, and Zn in stalks were significantly correlated with DTPA Zn in bulk soil, microaggregates, and large macroaggregates. CONCLUSIONS: Long-term application of horse manure could increase soil Zn availability and uptake by corn, possibly due to its activation by SOC. In contrast, chemical fertilizer application increased DTPA extractable Fe, Mn, and Cu in soil by reducing soil pH. Our results also suggest that Mn uptake by corn originated mainly in microaggregates, whereas Zn in crops was primarily sourced from large macroaggregates and microaggregates. PMID- 22293911 TI - "I don't think we're in Kansas anymore, Toto". PMID- 22293912 TI - Pyrazine alkaloids via dimerization of amino acid-derived alpha-amino aldehydes: biomimetic synthesis of 2,5-diisopropylpyrazine, 2,5-bis(3-indolylmethyl)pyrazine and actinopolymorphol C. AB - The dimerization of amino acid-derived alpha-amino aldehydes provides a short, biomimetic synthesis of several 2,5-disubstituted pyrazine natural products. The alpha-amino aldehyde intermediates were generated in situ by the hydrogenolysis of their Cbz-derivatives. It was found that a judicious choice of reaction solvent facilitated hydrogenolysis, dimerization and oxidation to the natural product in a one-pot operation. This methodology demonstrates the viability of a recently proposed, alternative biosynthetic route to 2,5-disubstituted pyrazines in nature. Furthermore, this work describes a novel, concise approach to pyrazines from alpha-amino aldehydes derived from readily available, cheap amino acids. PMID- 22293913 TI - Oxide nanowires for spintronics: materials and devices. AB - Spintronics, or spin-based data storage and manipulation technology, is emerging as a very active research area because of both new science and potential technological applications. As the characteristic lengths of spin-related phenomena naturally fall into the nanometre regime, researchers start applying the techniques of bottom-up nanomaterial synthesis and assembly to spintronics. It is envisaged that novel physics regarding spin manipulation and domain dynamics can be realized in quantum confined nanowire-based devices. Here we review the recent breakthroughs related to the applications of oxide nanowires in spintronics from the perspectives of both material candidates and device fabrication. Oxide nanowires generally show excellent crystalline quality and tunable physical properties, but more efforts are imperative as we strive to develop novel spintronic nanowires and devices. PMID- 22293914 TI - N-acetyl-3,4-dihydroxy-L-phenylalanine, a second identified bioactive metabolite produced by Streptomyces sp. 8812. PMID- 22293915 TI - Phytotoxic alpha-pyrones produced by Pestalotiopsis guepinii, the causal agent of hazelnut twig blight. PMID- 22293916 TI - Creatinine inhibits bacterial replication. PMID- 22293917 TI - Topical tacrolimus and 50% zinc oxide paste for Hailey-Hailey disease: less is more. PMID- 22293918 TI - Bmi-1 regulates autoreactive CD4+ T cell survival in immune thrombocytopenia patients. AB - Autoreactive T cells in immune thrombocytopenia(ITP) patients undergo a rapid clonal expansion and are resistant to apoptosis to maintain continuous effect in thrombocytopenia. As Bmi-1 is involved in memory CD4+ T cell survival and Th2 proliferation, we hypothesized that Bmi-1 may have a role in autoreactive CD4+ T cell clonal expansion and Th1/Th2 development in ITP patients. We found that CD4+ T cells from active ITP patients had a higher Bmi-1 expression in comparison with remission and healthy controls, and autoreactive CD4+ T cells had more capability to proliferate and resistance to apoptosis than that of healthy controls. We evaluated the part that Bmi-1 played in proliferation and Th1 bias condition of autoreactive CD4+ T cells in ITP. We used lentiviral transfer vectors containing Bmi-1 and shBmi-1 to infect CD4+ T cells from ITP patients and healthy controls during autologous platelets stimulation. Flow cytometry and ELISA were applied to detect various parameters. The results showed that suppression of Bmi-1 using short hairpin RNA inhibited the platelet-mediated proliferation and increased apoptosis of autoreactive CD4+ T cells from ITP patients.Increased Bmi-1 expression in CD4+ T cells from healthy controls promoted the proliferation and inhibited apoptosis of CD4+ T cells. Bmi-1 significantly promoted interleukin-4 secretion by CD4+ T cells. These findings suggest that Bmi-1 plays a part in autoreactive CD4+ T cell proliferative capability and apoptotic resistance in ITP patients. PMID- 22293919 TI - Spontaneous intracerebral hematoma: can we move beyond clot's removal? PMID- 22293920 TI - Airway management and tracheal intubation: where can we improve? PMID- 22293921 TI - Scoring prognostic system: to predict or not to predict. PMID- 22293922 TI - Bridging to lung transplantation by extracorporeal support. AB - Ideally, bridging patients with end stage severe respiratory failure to lung transplantation should significantly extend the pretransplant life expectancy to increase the chances to receive a suitable organ, as well as efficiently preserve the post-transplant long-term life expectancy by maintaining physiological homeostasis and avoiding multi-organ dysfunction. Various advanced strategies of extracorporeal circulation can replace at least in part the respiratory function of the lung and can potentially provide the appropriate mode and level of cardiopulmonary support for each patient's physiologic requirements. Therefore, patients on the lung transplant waiting list developing severe hypoxemic and/or hypercapnic respiratory failure can be supported for a prolonged period of time before the transplant, preserving a satisfactory post-transplant life expectancy. However, a more systematic clinical study on this issue is warranted in order to define the actual efficacy of these treatments in reducing the mortality rate on the waiting transplant list, and eventually improve the outcome of patients with end stage respiratory failure. PMID- 22293923 TI - Comments on "Continuous spinal anesthesia versus continuous femoral nerve block for elective total knee replacement". PMID- 22293925 TI - The importance of choosing the tracheostomy tube: how do we do it? PMID- 22293927 TI - A year in review in Minerva Anestesiologica 2011. PMID- 22293928 TI - Serum fibroblast growth factor 21 was elevated in subjects with type 2 diabetes mellitus and was associated with the presence of carotid artery plaques. AB - AIMS: Fibroblast growth factor 21 (FGF21) is an important regulator of glucose/lipid metabolism. Although there are studies examining the relationship between serum FGF21 levels and glucose homeostasis, the role of FGF21 remains unclear. The objective of this study was to examine whether serum FGF21 levels are associated with metabolic parameters in subjects with varying degrees of obesity and glucose tolerance and with complications in subjects with type2 diabetes mellitus (T2DM). METHODS: The study consisted of 213 subjects who were lean and had normal glucose tolerance (lean NGT), were overweight with NGT, had impaired glucose tolerance (IGT) or had T2DM. Serum FGF21 levels and their associations with the parameters of adiposity, glucose tolerance and the presence of diabetic complications were examined. RESULTS: The serum FGF21 levels in T2DM were higher than in lean NGT. Serum FGF21 levels showed a positive correlation with the urine albumin-to-creatinine ratio (ACR) in all subjects except for the T2DM subjects, who showed a correlation after adjustment of age, gender and body mass index. Moreover, the subjects with carotid artery plaque showed higher serum FGF21 levels than those without complications. CONCLUSION: Serum FGF21 levels were associated with the urine ACR and diabetic complications including carotid artery plaque. PMID- 22293929 TI - Chronic inflammatory demyelinating polyneuropathy mimicking diabetic neuropathy in a young female with type 2 diabetes mellitus. AB - The presentations of chronic inflammatory demyelinating polyneuropathy (CIDP) overlap with those of diabetic peripheral neuropathy (DPN). We described a young girl with CIDP underlying type 2 diabetes mellitus, presenting with progressive numbness and limb weakness, who was initially misdiagnosed to have DPN. Finally immunosuppressive therapy got good response. PMID- 22293930 TI - Non-adherence to diabetes guidelines in primary care - the enemy of evidence based practice. PMID- 22293931 TI - Naphthoylene(trifluoromethylbenzimidazole)-dicarboxylic acid imides for high performance n-type organic field-effect transistors. AB - 1,8-Naphthoylene(trifluoromethylbenzimidazole)-4,5-dicarboxylic acid imide (NTFBII) derivatives were synthesized. The OFET devices based on these new materials showed typical n-type OFET behavior and achieved an electron mobility as high as 0.10 cm(2) V(-1) s(-1) with good bias stress stability. PMID- 22293932 TI - Hypoxia and TP53 deficiency for induced pluripotent stem cell-like properties in gastrointestinal cancer. AB - Induced pluripotent stem (iPS)-like cancer cells (iPC) by the introduction of defined transcription factors reduce the prevalence of the malignant phenotype of digestive system cancer cells, but the induction efficiency is low. The role of hypoxia and TP53 deficiency in iPC cell generation remain unclear. Cellular reprogramming was performed by retroviral infection with OCT3/4, SOX2, KLF4 and c MYC of wild-type HCT116 colorectal cancer cells and mutant TP53-deficient HCT116 cells. Cells were cultured in normoxia (21% O2) or hypoxia (5% O2) for 30 days after transduction, and the response to hypoxia and comparison of cellular proliferation, invasion and tumourigenesis before and after iPC cell generation were studied. iPC cell generation from wild-type HCT116 cells in hypoxia was approximately 4-times greater than in normoxia (p<0.05), and TP53 deficiency increased conversion efficiency significantly in normoxia (p<0.05). Significant involvement of hypoxia-inducible factors was observed in an immature carbohydrate epitope, Tra-1-60+, colony formation. Generated iPC cells exhibited multi differentiation potential. Although the iPC cells in hypoxia exhibited reduced proliferation, invasiveness and tumourigenicity, TP53 deficiency in iPC cells resulted in higher tumourigenicity than in wild-type cells. Both hypoxia and TP53 deficiency increase iPC cell generation. TP53 deficiency can also result in deleterious mutations, whereas hypoxia may impact molecular targets of epigenome normalisation. PMID- 22293933 TI - Diagnosis and treatment of lupus nephritis. Consensus document from the systemic auto-immune disease group (GEAS) of the Spanish Society of Internal Medicine (SEMI) and Spanish Society of Nephrology (S.E.N.). PMID- 22293934 TI - Radical cystectomy for clinically muscle invasive bladder cancer: does prior non invasive disease affect clinical outcomes? AB - PURPOSE: To compare clinical and pathologic outcomes of radical cystectomy for muscle invasive bladder cancer in relation to prior history of non-invasive urothelial carcinoma. MATERIALS AND METHODS: Retrospective data collected from 1,150 patients managed by radical cystectomy for urothelial carcinoma of the bladder from the Canadian Bladder Cancer Network were analysed. Patients with clinical stage T2 or more were included and divided into two groups: (Group 1) patients with prior history of non-invasive urothelial carcinoma (N = 365) and (Group 2) patients with clinical muscle invasive cancer de novo (N = 785). Variables analysed included patient age, gender, pathologic stage, adjuvant chemotherapy, recurrence and mortality. RESULTS: Both groups were nearly equal in mean age and gender distribution, with mean ages of 67.2 and 66.7 years, and 79.7 and 79.5%, respectively (P = 0.4 and 0.9, respectively). The presence of preoperative hydronephrosis was 20.8 and 32.6% (P = 0.0007) for groups 1 and 2, respectively. The rate of higher pathological stage (T3 or T4) was 36.3 and 58% (P < 0.0001), positive lymph nodes were 20.1 and 28.8% (P = 0.002), and lymphovascular invasion was 31.7 and 46.2% (P = 0.0001) for groups 1 and 2, respectively. The rate of adjuvant chemotherapy was 15.5 and 23.3% (P = 0.002) for groups 1 and 2, respectively. None of the sampled patients received neoadjuvant chemotherapy. The overall survival (OS) and disease-specific survival (DSS) rates at 5 years were 62 and 70% for group 1 and 51 and 60% for group 2, respectively, while at 10 years, OS and DSS were 46 and 66% for group 1 and 35 and 49% for group 2, respectively (P = 0.0001 and 0.0002, respectively). Using multivariate analysis examining factors affecting recurrence and survival, we found that previous non-invasive bladder tumour history was associated with a significantly reduced risk of mortality and recurrence (Hazard ratio of 0.7 for all risks, P = 0.0002). CONCLUSION: Our retrospective study suggests that patients with non-invasive urothelial carcinoma of the bladder that progress to muscle invasion and require radical cystectomy appear to have better pathologic and clinical outcome than patients presenting with clinical muscle invasive disease de novo. PMID- 22293935 TI - Two-photon absorption of metal-organic DNA-probes. AB - We report remarkable multiphoton absorption properties of DNA intercalating ruthenium complexes: (1) [Ru(phen)(2)dppz](2+); (2) [(11,11' bidppz)(phen)(4)Ru(2)](4+); (3) [11,11'-bipb(phen)(4)Ru(2)](4+). Two-photon spectra in the range from 460 to 1100 nm were measured using the Z-scan technique. In particular, complex 2 was found to exhibit very strong two- and three-photon absorption properties, which could be an effect of symmetric charge transfer from the ends towards the middle of the conjugated dimeric orbital system. We propose that these molecules could provide a new generation of DNA binding nonlinear chromophores for wide applications in biology and material science. The combination of a large two-photon cross section and strong luminescence quantum yields for the molecules when intercalated makes the compounds uniquely bright and photo-stable probes for two-photon luminescence imaging and also promising as enhanced photosensitizers in two-photon sensitizing applications. PMID- 22293936 TI - NaCl taste thresholds in 13 inbred mouse strains. AB - Molecular mechanisms of salty taste in mammals are not completely understood. We use genetic approaches to study these mechanisms. Previously, we developed a high throughput procedure to measure NaCl taste thresholds, which involves conditioning mice to avoid LiCl and then examining avoidance of NaCl solutions presented in 48-h 2-bottle preference tests. Using this procedure, we measured NaCl taste thresholds of mice from 13 genealogically divergent inbred stains: 129P3/J, A/J, BALB/cByJ, C3H/HeJ, C57BL/6ByJ, C57BL/6J, CBA/J, CE/J, DBA/2J, FVB/NJ, NZB/BlNJ, PWK/PhJ, and SJL/J. We found substantial strain variation in NaCl taste thresholds: mice from the A/J and 129P3/J strains had high thresholds (were less sensitive), whereas mice from the BALB/cByJ, C57BL/6J, C57BL/6ByJ, CE/J, DBA/2J, NZB/BINJ, and SJL/J had low thresholds (were more sensitive). NaCl taste thresholds measured in this study did not significantly correlate with NaCl preferences or amiloride sensitivity of chorda tympani nerve responses to NaCl determined in the same strains in other studies. To examine whether strain differences in NaCl taste thresholds could have been affected by variation in learning ability or sensitivity to toxic effects of LiCl, we used the same method to measure citric acid taste thresholds in 4 inbred strains with large differences in NaCl taste thresholds but similar acid sensitivity in preference tests (129P3/J, A/J, C57BL/6J, and DBA/2J). Citric acid taste thresholds were similar in these 4 strains. This suggests that our technique measures taste quality-specific thresholds that are likely to represent differences in peripheral taste responsiveness. The strain differences in NaCl taste sensitivity found in this study provide a basis for genetic analysis of this phenotype. PMID- 22293937 TI - Stimulus selection for intranasal sensory isolation: eugenol is an irritant. AB - Both the olfactory and the trigeminal systems are able to respond to intranasal presentations of chemical vapor. Accordingly, when the nose detects a volatile chemical, it is often unclear whether we smell it, feel it, or both. The distinction may often be unimportant in our everyday perception of fragrances or aromas, but it can matter in experiments that purport to isolate olfactory processes or study the interaction between olfaction and chemesthesis. Researchers turn to a small pool of compounds that are believed to be "pure olfactory" stimuli with little or no trigeminal impact. The current report reexamines one such commonly used compound, namely eugenol, a flavor and fragrance ingredient that has anesthetic properties under some conditions. Using a standard method involving many trials during an experimental session (Experiment 1), subjects were unable to reliably lateralize eugenol, consistent with claims that this compound is detected primarily through olfaction. However, with more limited exposure (Experiments 2 and 3), subjects were able to lateralize eugenol. We speculate that anesthetic properties of eugenol could blunt its trigeminal impact in some paradigms. Regardless, the current experiments suggest that eugenol can in fact stimulate the trigeminal nerve but in a complex concentration-dependent manner. Implications and strategies for selection of model odorants are discussed. PMID- 22293938 TI - Bilayer graphene on h-BN substrate: investigating the breakdown voltage and tuning the bandgap by electric field. AB - By performing density functional theory calculations we show that it is possible to make the electronic bandgap in bilayer graphene supported on hexagonal boron nitride (h-BN) substrates tunable. We also show that, under applied electric fields, it is possible to insert states from h-BN into the bandgap, which generate a conduction channel through the substrate making the system metallic. In addition, we verify that the breakdown voltage strongly depends on the number of h-BN layers. We also show that both the breakdown voltage and the bandgap tuning are independent of the h-BN stacking order. PMID- 22293939 TI - An ICT-based strategy to a colorimetric and ratiometric fluorescence probe for hydrogen sulfide in living cells. AB - We present a colorimetric and ratiometric fluorescent probe Cy-N(3) that exhibits a selective response to H(2)S. The probe employs a near-infrared cyanine as a fluorophore, and is equipped with an operating azide unit. It is readily employed for assessing intracellular H(2)S levels, and confocal ratiometric imaging is achieved successfully. PMID- 22293940 TI - Editorial: Tim-3 puts on the brakes. PMID- 22293941 TI - Editorial: T cell memory, bone marrow, and aging: the good news. PMID- 22293942 TI - Association of glutathione S-transferase Omega 1-1 polymorphisms (A140D and E208K) with the expression of interleukin-8 (IL-8), transforming growth factor beta (TGF-beta), and apoptotic protease-activating factor 1 (Apaf-1) in humans chronically exposed to arsenic in drinking water. AB - Human exposure to arsenicals is associated with inflammatory-related diseases including different kinds of cancer as well as non-cancerous diseases like neuro degenerative diseases, atherosclerosis, hypertension, and diabetes. Interindividual susceptibility has been mainly addressed by evaluating the role of genetic polymorphism in metabolic enzymes in inorganic arsenic (iAs) metabolism. Glutathione S-transferase omega 1-1 (GSTO1-1), which had been associated with iAs metabolism, is also known to participate in inflammatory and apoptotic cellular responses. The polymorphism A140D of GSTO1-1 has been not only associated with distinct urinary profile of arsenic metabolites in populations chronically exposed to iAs in drinking water, but also with higher risk of childhood leukemia and lung disease in non-exposed populations, suggesting that GSTO1-1 involvement in other physiologic processes different from toxics metabolism could be more relevant than is thought. We evaluated the association of the presence of A140D and E208K polymorphisms of GSTO1-1 gene with the expression of genes codifying for proteins involved in the inflammatory and apoptotic response in a human population chronically exposed to iAs through drinking water. A140D polymorphism was associated with higher expression of genes codifying for IL-8 and Apaf-1 mainly in heterozygous individuals, while E208K was associated with higher expression of IL-8 and TGF- gene, in both cases, the association was independently of iAs exposure level; however, the exposure to iAs increased slightly but significantly the influence of A140D and E208K polymorphisms on such genes expression. These results suggest an important role of GSTO1-1 in the inflammatory response and the apoptotic process and indicate that A140D and E208K polymorphisms could increase the risk of developing inflammatory and apoptosis-related diseases in As-exposed populations. PMID- 22293943 TI - Tailoring the charge carrier dynamics in ZnO nanowires: the role of surface hole/electron traps. AB - Post-fabrication thermal-annealed ZnO nanowires (NWs) in an oxidizing (or a reducing) ambient were investigated using transient photoluminescence and X-ray photoelectron spectroscopy. Our findings reveal an ultrafast hole-transfer process to the surface adsorbed oxygen species (e.g., O(2)(-)) occurring within a few hundred picoseconds (ps) in the air-annealed samples; and an ultrafast electron-transfer process to charged oxygen vacancies (i.e., V(O)(2+)) occurring within tens of ps in the H(2)-annealed samples. Contrary to the common perception that the band edge emission (BE) dynamics are strongly influenced by the carrier trapping to the green emission related defect states (i.e., V(Zn)), these above processes compete effectively with the ZnO BE. Hole trapping by ionized V(Zn), which occurs in an ultrashort sub-ps-to-ps timescale (and hence limits its effective hole capture radius), however, has less influence on the BE dynamics. Importantly, our findings shed new light on the photoinduced charge transfer processes that underpins the novel properties of enhanced photocatalytic activity, photovoltaic performance, and photoconductivity response of ZnO NWs, thereby suggesting a strategy for tailoring the ultrafast carrier dynamics in ZnO NW-based devices. PMID- 22293944 TI - Insights into a surprising reaction: the microwave-assisted direct esterification of phosphinic acids. AB - It is well-known that phosphinic acids do not undergo direct esterifications with alcohols under thermal conditions. However, the esterifications take place under microwave (MW) irradiation due to the beneficial effect of MW. As a comparison, maximum 12-15% conversions were observed on traditional heating. It was proved experimentally that the MW-assisted esterifications are not reversible under the conditions applied that may be the consequence of the hydrophobic medium established by the long chain alcohol/phosphinic ester. Neither the thermodynamic, nor the kinetic data obtained by high level quantum chemical calculations justify the direct esterification of phosphinic acids under thermal conditions. The thermodynamic data show that there is no driving force for the reactions under discussion. As a consequence of the relatively high values of activation enthalpy (102-161 kJ mol(-1)), these esterifications are controlled kinetically. Comparing the energetics of the esterification of phosphinic acids and the preparative results obtained under MW conditions, one can see the potential of the MW technique in the synthesis of phosphinates. During our study, a series of new cyclic phosphinates with lipophilic alkyl groups was synthesized. PMID- 22293945 TI - Phenotyping of pulmonary carcinoids and a Ki-67-based grading approach. AB - Pulmonary carcinoids (PC) are separated into typical (TC) and atypical carcinoids (ATC). However, the biological behavior cannot be reliably predicted, and in small biopsies differential diagnosis can be challenging. To provide a basis for a grading approach, we analyzed mitoses and the proliferative index (PI; Ki-67) of 200 PC specimens (TC: n = 114; ATC: n = 86). To define suitable diagnostic and to screen for putative therapeutic markers, CD56, CD57, CD99, CD117, TTF-1, synaptophysin, chromogranin A, CK 18, KL-1, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (Her-2/neu), somatostatin receptor subtype 2A (SSTR2A), thymidylate synthase (TS), and excision repair cross-complementation group 1 (ERCC-1) expression was analyzed. A combination of synaptophysin and cytokeratins is the most sensitive marker panel for PC with unclear histomorphology. Predictive phenotyping revealed that SSTR2A is expressed in >80% of all PC and may be used both, as a diagnostic marker for imaging approaches and as a predictive marker for octreotide-based therapies. We introduced a grading system distinguishing between PC with low and highly aggressive biological behavior similar to the grading system for gastrointestinal neuroendocrine tumors. The system is superior to the classical separation into TC and ATC. This study indicates that PI in addition to mitotic count may improve prediction of the biological behavior of PC and should be validated in prospective studies. PMID- 22293946 TI - Segmentation and quantification of intra-ventricular/cerebral hemorrhage in CT scans by modified distance regularized level set evolution technique. AB - PURPOSE: An automatic, accurate and fast segmentation of hemorrhage in brain Computed Tomography (CT) images is necessary for quantification and treatment planning when assessing a large number of data sets. Though manual segmentation is accurate, it is time consuming and tedious. Semi-automatic methods need user interactions and might introduce variability in results. Our study proposes a modified distance regularized level set evolution (MDRLSE) algorithm for hemorrhage segmentation. METHODS: Study data set (from the ongoing CLEAR-IVH phase III clinical trial) is comprised of 200 sequential CT scans of 40 patients collected at 10 different hospitals using different machines/vendors. Data set contained both constant and variable slice thickness scans. Our study included pre-processing (filtering and skull removal), segmentation (MDRLSE which is a two stage method with shrinking and expansion) with modified parameters for faster convergence and higher accuracy and post-processing (reduction in false positives and false negatives). RESULTS: Results are validated against the gold standard marked manually by a trained CT reader and neurologist. Data sets are grouped as small, medium and large based on the volume of blood. Statistical analysis is performed for both training and test data sets in each group. The median Dice statistical indices (DSI) for the 3 groups are 0.8971, 0.8580 and 0.9173 respectively. Pre- and post-processing enhanced the DSI by 8 and 4% respectively. CONCLUSIONS: The MDRLSE improved the accuracy and speed for segmentation and calculation of the hemorrhage volume compared to the original DRLSE method. The method generates quantitative information, which is useful for specific decision making and reduces the time needed for the clinicians to localize and segment the hemorrhagic regions. PMID- 22293947 TI - Joint effect of polymorphism in the N-acetyltransferase 2 gene and smoking on hepatocellular carcinoma. AB - The N-acetyltransferase 2 gene (NAT2) has been implicated in the development of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, the authors performed a meta-analysis to clarify the association between NAT2 polymorphism and HCC risk. Published literatures from PubMed, EMBASE, CNKI, and Wan Fang Data were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Eight studies including 1,084 HCC cases and 1,682 controls were identified for the data analysis. The overall result showed that there was no statistically significant association between NAT2 genotypes and HCC risk (slow acetylation vs. rapid/intermediate acetylation: OR01.03, 95% CI 0.86-1.24). In the stratified analyses, NAT2 genotypes were also not significantly associated with HCC risk among both Europeans (OR01.11, 95% CI 0.86-1.43) and East Asians (OR01.01, 95% CI 0.65-1.56). Further subgroup analyses based on the smoking status showed that the effect size was statistically significant among the smokers (OR02.09, 95% CI 1.07 4.09), but not among those who never smoked (OR01.26, 95% CI 0.88-1.82). The present meta-analysis indicated that NAT2 genotypes were not associated with increased risk of HCC among the overall population but increased the risk of HCC among the smokers. PMID- 22293948 TI - Effects on apoptosis and cell cycle arrest contribute to the antitumor responses of interleukin-27 mediated by retrovirus in human pancreatic carcinoma cells. AB - Interleukin (IL)-27, composed of p28 and Epstein-Barr virus-induced gene 3 (EBI3) subunits, has diverse functions in regulating immune systems. Human melanoma cells have been shown to express both IL-27 receptor subunits, and growth inhibition by IL-27 was detected. We investigated whether forced expression of the p28-linked EBI3 gene in human pancreatic carcinoma cells (AsPC1) by retroviral vector would produce IL-27-mediated antitumor effects and the related mechanisms. The data demonstrated that AsPC1 cells expressed both IL-27 receptor subunits, and tumor growth of AsPC1/IL-27 in mice was retarded compared with vector DNA-transduced tumors and survival of the mice was prolonged. Expression of cytokines such as interferon-gamma, tumor necrosis factor-alpha and IL-1beta in tumor specimens increased, while the secretion of IFN-gamma and TNF-alpha from spleen cells of mice bearing IL-27-transfected tumors increased. Moreover, cell cycle arrest was induced in AsPC1/IL-27 inoculated mice with upregulated p21 expression and downregulated survivin expression. The appearance of apoptotic cells increased in tumor specimens of mice bearing IL-27-transfected tumors compared with the mice bearing DNA-transfected tumors by confirming the expression of apoptosis-related proteins and activated apoptotic pathways through detection of cleaved PARP. These results suggest that transfection of the IL-27 gene into human pancreatic carcinoma cells could produce antitumor effects in vivo and induction of cell cycle arrest and apoptosis could be the mechanism of IL-27 action in tumor regression. PMID- 22293949 TI - Island nucleation, optical and ferromagnetic properties of vertically aligned secondary growth ZnO : Cu nanorod arrays. AB - The paper reports an island nucleation and secondary growth of aligned ZnO : Cu nanorod arrays via thermal vapor phase transport. Results analysis indicates that the secondary segment is epitaxially grown on the ZnO : Cu nanorods with the radius strongly dependent on temperature and the concentration of zinc vapor. The modified characteristic radius (R(c)) model is used to explain the nucleation and secondary growth process. Temperature-dependent photoluminescence spectra indicate that the band gap emission of the secondary growth nanorods is greatly restrained. A controversial 3.31 eV emission (A line) and two different donor acceptor pair (DAP) recombinations at 3.24 eV and 2.48 eV are observed at 13 K. The A line shows a different behavior from the two DAP emissions during the heat up process. Intrinsic room temperature ferromagnetism (RTFM) is observed in the secondary growth ZnO : Cu nanorods and it can be explained by oxygen vacancy and copper defects related to bound magnetic polar (BMP) or double exchange mechanism. PMID- 22293950 TI - Distinct peak at 3.8 ppm observed by 3T MR spectroscopy in meningiomas, while nearly absent in high-grade gliomas and cerebral metastases. AB - The purpose of the present study was to evaluate distinct metabolic features of meningiomas to distinguish them from other brain lesions using proton magnetic resonance spectroscopy. The study was performed on 17 meningiomas, 24 high-grade gliomas and 9 metastases. Elevated signal intensity at 3.8 ppm observed in low TE spectra adequately differentiated meningioma from other brain tumors while alanine was not indicative of meningioma occurrence; the presence of lipids and lactate did not provide a strong index for meningioma malignancy. PMID- 22293951 TI - Roles of microRNAs and other non-coding RNAs in breast cancer metastasis. AB - Despite the fact that metastases are responsible for the overwhelming majority of human cancer deaths, our comprehension of the molecular events that drive metastatic progression remains woefully incomplete. Excitingly, the recent appreciation that various species of non-coding RNAs-including microRNAs-play pivotal roles in dictating the malignant behaviors of breast carcinoma cells promises to afford new insights into the molecular circuitry that determines metastatic propensity. Here, I summarize our current knowledge regarding these still-emerging functions for non-coding RNAs in the pathogenesis of breast cancer metastasis, with an emphasis placed upon the roles played by microRNAs in these processes. Additionally, I discuss the potential translational opportunities afforded by these research findings for the diagnosis and treatment of human breast tumors. When assessed collectively, it is apparent that although this field of research is still in its infancy, comprehension of the biological actions of microRNAs and other non-coding RNAs will hold important consequences for our understanding of the etiology of metastatic disease, as well as its clinical management and treatment. PMID- 22293952 TI - Ventriculoperitoneal shunt catheter protrusion through the anus: case report of an uncommon complication and literature review. PMID- 22293953 TI - Grisel's syndrome: a comprehensive review with focus on pathogenesis, natural history, and current treatment options. PMID- 22293954 TI - Penetration patterns of monomeric and polymeric 1,6-hexamethylene diisocyanate monomer in human skin. AB - We investigated penetration patterns of monomeric and polymeric 1,6-hexamethylene diisocyanate (HDI), experimentally and as part of commercial products, in excised full-thickness human skin at 5, 10, 30, or 60 min after exposure. We observed that both monomeric and polymeric HDI were readily absorbed into the skin and that the clearcoat composition affects the penetration rate of the individual isocyanates. The short-term absorption rates for HDI monomer, biuret, and isocyanurate were determined and used to estimate the exposure time required to reach a body burden equal to the American Conference of Governmental Industrial Hygienists (ACGIH) inhalation threshold limit value (TLV) or Oregon State occupational exposure limit (OEL). Oregon is the only government entity in the United States to promulgate a short-term exposure limit (STEL) for HDI-based polyisocyanates biuret and isocyanurate. Based on these absorption rates for a slow-drying clearcoat after 10 min (1.33 MUg cm(-2) h(-1)) or 60 min (0.219 MUg cm(-2) h(-1)), we calculated that 6.5 and 40 min dermal exposure, respectively, is required to achieve a dose of HDI equivalent to the ACGIH TLV. For biuret, the time to achieve a dose equivalent to the Oregon OEL for slow-drying clearcoat was much shorter (<31 min) than that for fast-drying clearcoat (618 min). Isocyanurate had the shortest skin absorption times regardless of clearcoat formulation (14 s-1.7 min). These results indicate that the dose received through dermal exposure to HDI-containing clearcoats has a significant potential to exceed the dose equivalent to that received through inhalation exposure at established regulatory limits. A critical need exists to monitor dermal exposure quantitatively in exposed workers, to use proper protective equipment to reduce dermal exposure, and to re-evaluate regulatory exposure limits for isocyanates. PMID- 22293955 TI - Photophysical and biological investigation of novel luminescent Ru(II) polypyridyl-1,8-naphthalimide Troger's bases as cellular imaging agents. AB - The synthesis and photophysical properties of 1 and 2, two Ru(II)-polypyridyl based-1,8-naphthalimide Troger's bases, are described; these were found to stabilize double stranded DNA, undergo rapid cellular uptake, displaying good luminescence without affecting cell viability even after 24 hours of incubation. PMID- 22293956 TI - Multiple blisters along the lip vermilion are a clue to bullous lupus erythematosus. PMID- 22293957 TI - ERK and Akt signaling pathways are involved in advanced glycation end product induced autophagy in rat vascular smooth muscle cells. AB - Advanced glycation end products (AGEs) play an important role in the proliferation of vascular smooth muscle cells (VSMCs) and accelerate atherosclerosis in diabetic patients. Autophagy, a life-sustaining process, is stimulated in atherosclerotic plaques by oxidized lipids, inflammation and metabolic stress conditions. In our studies, we utilized MTT assays to show that autophagy is involved in AGE-induced proliferation of VSMCs. Furthermore, treatment with AGEs (100 ug/ml) could induce autophagy in a time- and dose dependent manner in rat aortic VSMCs. These results were further substantiated by electron microscopy and immunofluorescence imaging. Treatment with AGEs activated ERK, JNK and p38/MAPK, but inhibited Akt. Pretreatment with an ERK inhibitor and an Akt activator inhibited AGE-induced autophagy, demonstrating that AGEs induce autophagy in VSMCs through the ERK and Akt signaling pathways. In addition, RNA interference of RAGE decreased autophagy, indicating that RAGE is pivotal in the process of AGE-induced autophagy. Therefore, AGE-induced autophagy contributes to the process of AGE-induced proliferation of VSMCs, which is related to atherosclerosis in diabetes. PMID- 22293958 TI - delta-Aminolevulinate synthase is required for apical transcellular barrier formation in the skin of the Drosophila larva. AB - Animals construct a layered skin to prevent dehydration and pathogen entrance. The barrier function of the skin relies on the extensive cross-linking of specialised components. In insects, for instance, epidermal cells produce an apical extracellular cuticle that consists of a network of proteins, chitin and lipids. We have identified mutations in the Drosophila gene coding for the delta aminolevulinate synthase (Alas) that cause massive water loss. The cuticle of alas mutant larvae detaches from the epidermis and its basal region is frayed suggesting that an Alas dependent pathway is needed to organise the contact between the cuticle and the epidermis and anchor the cuticle to the apical surface of epidermal cells. Concomitantly, reduction of Alas function results in weakening of the extracellular dityrosines network in the cuticle, whereas glutamyl-lysine isopeptide bonds are not affected. The lateral septate junctions of epidermal cells that serve as a paracellular plug are intact, as well. Taken together, we hypothesise that Alas activity, which initiates heme biosynthesis in the mitochondrion, is needed for the formation of a dityrosine-based barrier that confers resistance to the internal hydrostatic pressure protecting both the cuticle from transcellular infiltration of body fluid and the animal from dehydration. We conclude that at least two modules--an apical protein-chitin lattice and the lateral septate junctions, act in parallel to ensure Drosophila skin impermeability. PMID- 22293959 TI - Protoporphyrin IX-dependent photodynamic production of endogenous ROS stimulates cell proliferation. AB - Photodynamic therapy using methyl 5-aminolevulinate (MAL) as a precursor of the photosensitizing agent protoporphyrin IX is widely used in clinical practice for the treatment of different pathologies, including cancer. In this therapeutic modality, MAL treatment promotes the forced accumulation of the endogenous photoactive compound protoporphyrin IX in target malignant cells. Subsequent irradiation of treated tissues with an appropriate visible light source induces the production of reactive oxygen species (ROS) that, once accumulated above a critical level, promote cell death. Here we demonstrate that a photodynamic treatment with low MAL concentrations can be used to promote a moderate production of endogenous ROS, which efficiently stimulates cell growth in human immortalized keratinocytes (HaCaT). We also show that this proliferative response requires Src kinase activity and is associated to a transient induction of cyclin D1 expression. Taken together, these results demonstrate for the first time that a combination of light and a photoactive compound can be used to modulate cell cycle progression through Src kinase activation and that a moderate intracellular increase of photogenerated ROS efficiently stimulates cell proliferation. PMID- 22293960 TI - In situ hybridization to cellular RNA. AB - In situ hybridization to cellular RNA is used to determine the cellular localization of specific messages within complex cell populations and tissues. Tissues may either be embedded in paraffin and sectioned on a microtome (see Hybridization Using Paraffin Sections and Cells), or frozen and sectioned in a cryostat (see Hybridization Using Cryosections). RNA contained in the specimens is hybridized to a specific radiolabeled probe (see Synthesis of (35)S-Labled Riboprobes and Synthesis of (35)S-Labled Double-Stranded DNA Probes), which is then detected using film autoradiography or emulsion autoradiography (Chapter 8). PMID- 22293961 TI - Characterization of the picrotoxin site of GABAA receptors. AB - This protocol describes an in vitro assay for characterization of the picrotoxin site of GABA(A) receptors in rat brain membranes using various radioligands. Methods and representative data for Scatchard analysis (Kd, Bmax determination), association kinetics, dissociation kinetics and competition assays (IC50, Ki determination) are included in the protocol. PMID- 22293962 TI - [3H](+)MK801 radioligand binding assay at the N-methyl-D-aspartate receptor. AB - The N-methyl-D-aspartate subtype of glutamate receptor is unusual in that it requires two endogenous agonists for activation. Thus, in addition to glutamate, the amino acid glycine (or possibly D-serine) is an essential co-agonist. This unit presents a radioligand binding protocol that detects ligand activity at the NMDA receptor-associated glycine site. This is a convenient approach that exploits the ability of NMDA receptor modulators to alter the kinetics of ligands that bind to the channel-blocking site of the NMDA receptor. This protocol takes advantage of one of the most potent and specific ligands that bind to this receptor, in this case [(3)H](+)MK801. Importantly, this assay can detect and differentiate agonists and antagonists that bind to the glycine site. A protocol for the measurement of glycine site activity with [(3)H](+)MK801 binding is provided, along with support protocols that provide information to aid in the design of assays of agonists and antagonists of the glycine site, and data analysis. PMID- 22293963 TI - Vigilance-controlled quantified EEG in safety pharmacology. AB - The vigilance-controlled quantified EEG can be used either as a safety, or as a discovery pharmacology procedure. Put strategically into the preclinical development process of a drug, it can be useful for making the decision about the future research direction to be taken. The experimental approach described in this unit is based on the rat EEG. Even though there are considerable differences in function and structure between human and rat brain, the EEG response to psychoactive drugs and convulsants is similar in the two species. Thus, the rat EEG is generally a reliable predictor for human CNS drug effects. PMID- 22293964 TI - Monoamine oxidase assays. AB - Monoamine oxidase catalyzes the oxidative deamination of primary aliphatic and aromatic amines and some secondary and tertiary amines, including the hormone and neurotransmitter amines epinephrine, dopamine, norepinephrine and serotonin. The two isoenzymes, MAO-A and MAO-B, differ according to substrate and inhibitor specificities. For example, selective inhibitors of MAO-A have been shown to be effective antidepressants whereas some MAO-B inhibitors have been reported to be beneficial in the treatment of Parkinson's and perhaps Alzheimer's diseases. Thus, it is important to have accurate procedures for determining the activities of each MAO isoenzyme in tissues that may contain both. In this unit, several MAO assay procedures are described, along with support protocols for equilibrating ion-exchange resin, preparing aldehyde dehydrogenase, preparing dose-response curves for determining the relative proportions of isoenzyme activities, determining concentrations of each isoenzyme, assessing new compounds as putative MAO inhibitors, and determining protein concentration of membrane-bound proteins. PMID- 22293965 TI - Cysteinyl leukotriene receptor assays. AB - The cysteinyl leukotrienes (CysLTs), LTC4, LTD4 and LTE4, lipid products derived from arachidonic acid metabolism, have been implicated in the pathophysiology of several inflammatory diseases, in particular, asthma. This unit describes techniques and applications for the measurement of contractile responses to the CysLTs in isolated smooth muscle preparations. The contractions are assessed by standard methods for the isometric measurement of responses (contractile or relaxant) of isolated tissues to exogenous agonists, and a detailed description of the methods employed to assess CysLT-induced contractions in guinea-pig trachea is outlined. However, the same general methodology (other than parameters such as dissection for non-airway tissues) are appropriate for measuring CysLT induced contractions in airway preparations from other animals, and in non airways tissues (e.g., the gastrointestinal tract) from different species, and also in exploring the relaxant responses to the CysLTs that have been demonstrated in some tissues (e.g., pulmonary vein or artery). PMID- 22293966 TI - Estimating intestinal mucosal permeation of compounds using Caco-2 cell monolayers. AB - Step-by-step protocols are provided in this unit for the measurement of apparent permeability coefficients of compounds using Caco-2 cell monolayers as an in vitro model of the intestinal mucosa. Procedures for culturing the cells and transmonolayer transport studies are also included. Critical issues for successfully estimating intestinal mucosal permeation of drugs are discussed. Step-by-step protocols are provided in this unit for the measurement of apparent permeability coefficients of compounds using. PMID- 22293967 TI - Cell-based assays using the fluorometric imaging plate reader (FLIPR). AB - A critical component of the drug discovery and development process is the identification of novel pharmacophores. Such discovery efforts are, in general, facilitated by rapid and high-throughput cell-based assays of receptor/ion channel-mediated signaling processes to screen diverse chemical libraries of compounds possessing activator or inhibitor activities at the desired target. The availability of the Fluorometric Image Plate Reader (FLIPR) has made rapid assays of cellular signaling processes feasible by simultaneous kinetics measurement of cell-based fluorescence changes in a 96- or 384-well format. This unit describes the application of the FLIPR in cell-based kinetic assays for measuring membrane potential changes and intracellular calcium dynamics. PMID- 22293968 TI - Overview of combinatorial chemistry. AB - This unit provides an overview of combinatorial chemistry, including the design and construction of combinatorial libraries for drug discovery. Strategies and resources for library synthesis are summarized, and examples of combinatorial libraries are given. This unit provides an overview of combinatorial chemistry, including the design and construction of combinatorial libraries fo. PMID- 22293969 TI - Particle size measurement of lipoprotein fractions using diffusion-ordered NMR spectroscopy. AB - The sizes of certain types of lipoprotein particles have been associated with an increased risk of cardiovascular disease. However, there is currently no gold standard technique for the determination of this parameter. Here, we propose an analytical procedure to measure lipoprotein particles sizes using diffusion ordered nuclear magnetic resonance spectroscopy (DOSY). The method was tested on six lipoprotein fractions, VLDL, IDL, LDL1, LDL2, HDL2, and HDL3, which were obtained by sequential ultracentrifugation from four patients. We performed a pulsed-field gradient experiment on each fraction to obtain a mean diffusion coefficient, and then determined the apparent hydrodynamic radius using the Stokes-Einstein equation. To validate the hydrodynamic radii obtained, the particle size distribution of these lipoprotein fractions was also measured using transmission electron microscopy (TEM). The standard errors of duplicate measurements of diffusion coefficient ranged from 0.5% to 1.3%, confirming the repeatability of the technique. The coefficient of determination between the hydrodynamic radii and the TEM-derived mean particle size was r2 = 0.96, and the agreement between the two techniques was 85%. Thus, DOSY experiments have proved to be accurate and reliable for estimating lipoprotein particle sizes. PMID- 22293970 TI - A fluorescence chemosensor based on peptidase for detecting nickel(II) with high selectivity and high sensitivity. AB - We report herein a new class of metal ion chemosensors and give the first example of a metal-dependent peptidase chemosensor for metal ions. The chemosensor contains the basic specific Ni(II)-dependent peptide bond hydrolysis sequence (Gly-Ala-Ser-Arg-His-Trp-Lys-Phe-Lys). The substrate was labeled with a fluorophore at the N-terminal and a quencher at the C-terminal Lys side chain. Initially, the MOCAc ((7-methoxycoumarin-4-yl)acetyl-) emission was quenched by the nearby quencher. In the presence of Ni(II), the substrate was irreversibly cleaved at the cleavage site, leading to a 20-fold increase in fluorescence intensity. The chemosensor combines the high selectivity of a peptidase (at least greater than tenfold for Ni(II) over other metal ions) with the high sensitivity of fluorescence detection limit of 50 nM and can be applied for the quantitative detection of Ni(II) over a concentration range of three orders of magnitude. Given this degree of selectivity and sensitivity, our molecular engineering design may prove useful in the future development of other peptidase-based probes for different metal ions in toxicological and environmental monitoring. PMID- 22293971 TI - Stable isotope dilution assay for the accurate determination of mycotoxins in maize by UHPLC-MS/MS. AB - A fast, easy-to-handle and cost-effective analytical method for 11 mycotoxins currently regulated in maize and other cereal-based food products in Europe was developed and validated for maize. The method is based on two extraction steps using different acidified acetonitrile-water mixtures. Separation is achieved using ultrahigh-performance liquid chromatography (UHPLC) by a linear water methanol gradient. After electrospray ionisation, tandem mass spectrometric detection is performed in dynamic multiple reaction monitoring mode. Since accurate mass spectrometric quantification is hampered by matrix effects, uniformly [(13)C]-labelled mycotoxins for each of the 11 compounds were added to the sample extracts prior to UHPLC-MS/MS analysis. Method performance parameters were obtained by spiking blank maize samples with mycotoxins before as well as after extraction on six levels in triplicates. The twofold extraction led to total recoveries of the extraction steps between 97% and 111% for all target analytes, including fumonisins. The [(13)C]-labelled internal standards efficiently compensated all matrix effects in electrospray ionisation, leading to apparent recoveries between 88% and 105% with reasonable additional costs. The relative standard deviations of the whole method were between 4% and 11% for all analytes. The trueness of the method was verified by the measurement of several maize test materials with well-characterized concentrations. In conclusion, the developed method is capable of determining all regulated mycotoxins in maize and presuming similar matrix effects and extraction recovery also in other cereal based foods. PMID- 22293972 TI - P21-activated protein kinase 1 is overexpressed in gastric cancer and induces cancer metastasis. AB - P21-activated protein kinase (Pak1), a main downstream effector of small Rho GTPases, plays an important role in the regulation of cell morphogenesis, motility, mitosis and angiogenesis. However, the role of Pak1 in gastric cancer metastasis remains unclear. Here, we showed that Pak1 is overexpressed in gastric cancer tissues from 74 patients by immunohistochemistry. Overexpression of Pak1 was associated with metastasis and prognosis of gastric cancer. In addition, overexpression of Pak1 increased gastric cancer cell motility and invasion, whereas downregulation of Pak1 expression reduced gastric cancer cell migration and invasion. In further study, data showed that activated Pak1 inhibited stress fiber and focal adhesion complex formation in gastric cancer cells and led to the formation of motile phenotypes. Importantly, activated Pak1 elicited phosphorylation of the ERK and JNK-dependent pathway in gastric cancer cell lines. In conclusion, our results suggest that Pak1 is overexpressed in gastric cancer and plays an important role in the metastasis of gastric cancer. The mechanism by which Pak1 induces cancer metastasis may involve activation of ERK and JNK. PMID- 22293973 TI - Stimulating axonal regeneration of mature retinal ganglion cells and overcoming inhibitory signaling. AB - Like other neurons of the central nervous system (CNS), retinal ganglion cells (RGCs) are normally unable to regenerate injured axons and instead undergo apoptotic cell death. This regenerative failure leads to lifelong visual deficits after optic nerve damage and is partially attributable to factors located in the inhibitory environment of the forming glial scar and myelin as well as to an insufficient intrinsic ability for axonal regrowth. In addition to its ophthalmological relevance, the optic nerve has long been used as a favorable paradigm for studying regenerative failure in the CNS as a whole. Findings over the last 15 years have shown that, under certain circumstances, mature RGCs can be transformed into an active regenerative state enabling these neurons to survive axotomy and to regenerate axons in the optic nerve. Moreover, combinatorial treatments overcoming the inhibitory environment of the glial scar and optic nerve myelin, together with approaches activating the intrinsic growth program, can further enhance the amount of regeneration in vivo. These findings are encouraging and open the possibility that clinically meaningful regenerationmay become achievable in the future. PMID- 22293974 TI - Validation of a high-throughput microtissue fabrication process for 3D assembly of tissue engineered cartilage constructs. AB - Described here is a simple, high-throughput process to fabricate pellets with regular size and shape and the assembly of pre-cultured pellets in a controlled manner into specifically designed 3D plotted porous scaffolds. Culture of cartilage pellets is a well-established process for inducing re-differentiation in expanded chondrocytes. Commonly adopted pellet culture methods using conical tubes are inconvenient, time-consuming and space-intensive. We compared the conventional 15-mL tube pellet culture method with 96-well plate-based methods, examining two different well geometries (round- and v-bottom plates). The high throughput production method was then used to demonstrate guided placement of pellets within a scaffold of defined pore size and geometry for the 3D assembly of tissue engineered cartilage constructs. While minor differences were observed in tissue quality and size, the chondrogenic re-differentiation capacity of human chondrocytes, as assessed by GAG/DNA, collagen type I and II immunohistochemistry and collagen type I, II and aggrecan mRNA expression, was maintained in the 96 well plate format and pellets of regular size and spheroidal shape were produced. This allowed for simple production of large numbers of reproducible tissue spheroids. Furthermore, the pellet-assembly method successfully allowed fluorescently labelled pellets to be individually visualised in 3D. During subsequent culture of 3D assembled tissue engineered constructs in vitro, pellets fused to form a coherent tissue, promoting chondrogenic differentiation and GAG accumulation. PMID- 22293975 TI - Histological and ultrastructural abnormalities in murine desmoglein 2-mutant hearts. AB - Mice carrying a deletion of the adhesive extracellular domain of the desmosomal cadherin desmoglein 2 develop an arrhythmogenic right ventricular cardiomyopathylike phenotype with ventricular dilation, fibrosis and arrhythmia. To unravel the sequence of myocardial alterations and to identify potential pathomechanisms, histological analyses were performed on mutant hearts from the juvenile to the adult state, i.e., between 2 and 13 weeks. At an age of 2 weeks 30% of mutants presented lesions,which were visible as white plaques on the heart surface or in the septum. From 4 weeks onwards, all mutants displayed a cardiac phenotype. Dying cardiomyocytes with calcification were found in lesions of all ages. But lesions of young mutant animals contained high amounts of CD45+ immune cells and little collagen fibers, whereas lesions of the older animals were collagen-rich and harbored only a small but still significantly increased number of CD45+ cells. Electron microscopy further showed that distinct desmosomes cannot be distinguished in intercalated discs of mutant hearts. Widening of the intercellular cleft and even complete dissociation of intercalated discs were often observed close to lesions. Disturbed sarcomer structure, altered Z-discs, multiple autophagic vacuoles and swollen mitochondria were other prominent pathological features. Taken together, the following scenario is suggested: mutant desmoglein 2 cannot fully support the increased mechanical requirements placed on intercalated disc adhesion during postnatal heart development, resulting in compromised adhesion and cell stress. This induces cardiomyocyte death, aseptic inflammation and fibrotic replacement. The acute stage of scar formation is followed by permanent impairment of the cardiac function. PMID- 22293976 TI - Nijmegen breakage syndrome with macrocephaly, schizencephaly and large CSF spaces extended spectrum of the condition. PMID- 22293977 TI - Fluorogenic sensing of CH3CO2- and H2PO4- by ditopic receptor through conformational change. AB - Cyclo-bis-(urea-3,6-dichlorocarbazole) (1) forms a 1 : 2 complex with CH(3)CO(2)( ) and H(2)PO(4)(-) through hydrogen bonding with the two urea moieties, resulting in fluorescence enhancement via a combined photoinduced electron transfer (PET) and energy transfer mechanism. The binding mechanism involves a conformational change of the two urea receptors to a trans orientation after binding of the first anion, which facilitates the second interaction. PMID- 22293978 TI - Closed-form inverse kinematics for interventional C-arm X-ray imaging with six degrees of freedom: modeling and application. AB - For trauma and orthopedic surgery, maneuvering a mobile C-arm fluoroscope into a desired position to acquire an X-ray is a routine surgical task. The precision and ease of use of the C-arm becomes even more important for advanced interventional imaging techniques such as parallax-free X-ray image stitching. Today's standard mobile C-arms have been modeled with only five degrees of freedom (DOF), which definitely restricts their motions in 3-D Cartesian space. In this paper, we present a method to model both the mobile C-arm and patient's table as an integrated kinematic chain having six DOF without constraining table position. The closed-form solutions for the inverse kinematics problem are derived in order to obtain the required values for all C-arm joint and table movements to position the fluoroscope at a desired pose. The modeling method and the closed-form solutions can be applied to general isocentric or nonisocentric mobile C-arms. By achieving this we develop an efficient and intuitive inverse kinematics-based method for parallax-free panoramic X-ray imaging. In addition, we implement a 6-DOF C-arm system from a low-cost mobile fluoroscope to optimally acquire X-ray images based solely on the computation of the required movement for each joint by solving the inverse kinematics on a continuous basis. Through simulation experimentation, we demonstrate that the 6-DOF C-arm model has a larger working space than the 5-DOF model. C-arm repositioning experiments show the practicality and accuracy of our 6-DOF C-arm system. We also evaluate the novel parallax-free X-ray stitching method on phantom and dry bones. Using five trials, results show that parallax-free panoramas generated by our method are of high visual quality and within clinical tolerances for accurate evaluation of long bone geometry (i.e., image and metric measurement errors are less than 1% compared to ground-truth). PMID- 22293979 TI - African American adolescents meeting sex partners online: closing the digital research divide in STI/HIV prevention. AB - Minority adolescents are affected disproportionately by HIV and STIs, and the Internet is a popular venue to meet sex partners. Little is known about the risks of this behavior for minority adolescents. The majority of studies that have examined sexual risk behavior online or STI/HIV prevention programs online have been among adult MSM. In this study, data from 1,045 African American youth found that 6% met sex partners online and in chat rooms. Odds ratios, adjusting for gender, found this behavior was associated with alcohol (AOR = 2.33, 95% CI [1.1, 4.7]) and drug use (AOR = 3.45, 95% CI [1.9, 6.1]), unprotected vaginal (AOR = 4.71, 95% CI [1.9, 8.4]) and anal sex (AOR = 4.77, 95% CI [1.3,17.1]) in the last 90 days, more lifetime vaginal (AOR = 3.65, 95% CI [2.0, 6.8]) and anal sex (AOR = 2.74, 95% CI [1.5, 4.8]), greater sexual sensation seeking (AOR = 2.92, 95% CI [1.5, 5.7]) and greater depression (AOR = 2.06, 95% CI [1.2, 3.6]. A final multiple logistic regression analyses found that male gender (AOR = 3.13, 95% CI [1.7, 5.8]), drug use at last sex (AOR = 2.41, 95% CI [1.3, 4.5]), lifetime history of vaginal (AOR = 2.90, 95% CI [1.5, 5.5]) and anal sex (AOR = 2.09, 95% CI [1.2, 3.6]), and cocaine use (AOR = 8.53, 95% CI [2.7, 27.3]) were independently associated with having sex with a partner met online. Meeting sex partners online is associated with a variety of risks among African American youth; however, the Internet may be an opportunity for intervention. PMID- 22293980 TI - A Theory of Planned Behavior research model for predicting the sleep intentions and behaviors of undergraduate college students. AB - The purpose of this study was to operationalize the constructs of the Theory of Planned Behavior (TPB) to predict the sleep intentions and behaviors of undergraduate college students attending a Midwestern University. Data collection spanned three phases. The first phase included a semi-structured qualitative interview (n = 11), readability by Flesch-Kincaid, face and content validity by a panel of six experts. The second phase included stability reliability by test retest (n = 37). The final phase included construct validation applying confirmatory factor analysis, internal consistency by Cronbach's alpha, and predictive validity (n = 197) employing multiple regression analysis. The majority of the participants reported receiving insufficient sleep (M = 407.3 min, SD = 100.75). Multiple regression modeled perceived behavioral control, subjective norm, and attitude toward adequate sleep behavior on behavioral intention. Collectively, the significant predictors produced an R(2)(adjusted) value of .362. Further specification of the model identified behavioral intention as a significant predictor of sleep behavior (R(2)(adjusted) = .185). As a population, undergraduate college students are not achieving adequate sleep. The TPB was found to be a useful framework for predicting the sleep intentions and behaviors of undergraduate students. Practical implications and recommendations for future research are discussed. PMID- 22293981 TI - Dominant free exciton emission in ZnO nanorods. AB - Nanostructured ZnO is considered to be a promising building block in the design of nanoscale optoelectronic devices. It usually shows dominant donor-bound exciton (DX) emission at low temperatures. In this study, ZnO nanorods with high crystallinity and optical quality were grown by metal-organic chemical vapor deposition on a-plane sapphire (1120) substrates. Dominant free exciton (FX) emission at a low temperature (14 K) was observed by photoluminescence spectroscopy. It was attributed to both the enhancement of the FX emission induced by the high crystalline quality of the nanorods and the suppression of the DX emission induced by hydrogen out-diffusion. The latter reason is believed to be more important from the analysis of the hydrogen distribution in the nanorods through photoluminescence spectroscopy and secondary ion mass spectrometry. A slow cooling process during the deposition is suggested to result in a better optical quality. These results can promote our understanding of the optical properties of ZnO nanostructures. PMID- 22293982 TI - A review of the relationships between extreme obesity, quality of life, and sexual function. AB - Extreme obesity is associated with significant health issues as well as substantial psychosocial burden for many individuals. Numerous studies have documented the impairments in quality of life associated with extreme obesity. Sexual behavior and functioning is an important aspect of quality of life but is frequently overlooked in research studies as well as clinical care. This paper focuses on the quality of life and sexual functioning of obese individuals with specific focus on the changes in these domains following the substantial weight losses seen after bariatric surgery. PMID- 22293984 TI - Control of brain capillary blood flow. AB - While it has been widely confirmed that cerebral blood flow is closely coupled with brain metabolism, it remains a matter of controversy whether capillary flow is directly controlled to meet the energy demands of the parenchyma. Since the capillary is known to lack smooth muscle cells, it has generally been considered that capillary flow is not regulated in situ. However, we now have increasing data supporting the physiological control of capillary flow. The observation of heterogeneity in the microcirculation in vivo has suggested that intravascular factors may be involved in the flow control, including non-Newtonian rheology, red blood cell flow, leukocyte adhesion, release of vasoactive mediators, and expression of glycoproteins on the endothelial cells. Astrocytes, a key mediator of the neurovascular unit, and intrinsic innervation may also regulate capillary flow. In addition, recent findings on pericyte contractility have attracted the attention of many researchers. Finally, based on these findings, we present a new model of flow control, the proximal integration model, in which localized neural activity is detected at nearby capillaries and the vasodilation signal is transmitted proximally along the vessel. Signals are then integrated at the precapillary arterioles and other arterioles further upstream and regulate the capillary flow. PMID- 22293985 TI - Pyramidal cells and cytochrome P450 epoxygenase products in the neurovascular coupling response to basal forebrain cholinergic input. AB - Activation of the basal forebrain (BF), the primary source of acetylcholine (ACh) in the cortex, broadly increases cortical cerebral blood flow (CBF), a response downstream to ACh release. Although endothelial nitric oxide and cholinoceptive GABA (gamma-aminobutyric acid) interneurons have been implicated, little is known about the role of pyramidal cells in this response and their possible interaction with astrocytes. Using c-Fos immunohistochemistry as a marker of neuronal activation and laser-Doppler flowmetry, we measured changes in CBF evoked by BF stimulation following pharmacological blockade of c-Fos-identified excitatory pathways, astroglial metabolism, or vasoactive mediators. Pyramidal cells including those that express cyclooxygenase-2 (COX-2) displayed c-Fos upregulation. Glutamate acting via NMDA, AMPA, and mGlu receptors was involved in the evoked CBF response, NMDA receptors having the highest contribution (~33%). In contrast, nonselective and selective COX-2 inhibition did not affect the evoked CBF response (+0.4% to 6.9%, ns). The metabolic gliotoxins fluorocitrate and fluoroacetate, the cytochrome P450 epoxygenase inhibitor MS-PPOH and the selective epoxyeicosatrienoic acids (EETs) antagonist 14,15-epoxyeicosa-5(Z) enoic acid (14,15-EEZE) all blocked the evoked CBF response by ~50%. Together, the data demonstrate that the hyperemic response to BF stimulation is largely mediated by glutamate released from activated pyramidal cells and by vasoactive EETs, likely originating from activated astrocytes. PMID- 22293983 TI - Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain. AB - The cerebral vascular system services the constant demand for energy during neuronal activity in the brain. Attempts to delineate the logic of neurovascular coupling have been greatly aided by the advent of two-photon laser scanning microscopy to image both blood flow and the activity of individual cells below the surface of the brain. Here we provide a technical guide to imaging cerebral blood flow in rodents. We describe in detail the surgical procedures required to generate cranial windows for optical access to the cortex of both rats and mice and the use of two-photon microscopy to accurately measure blood flow in individual cortical vessels concurrent with local cellular activity. We further provide examples on how these techniques can be applied to the study of local blood flow regulation and vascular pathologies such as small-scale stroke. PMID- 22293987 TI - Evolution of the dynamic changes in functional cerebral oxidative metabolism from tissue mitochondria to blood oxygen. AB - The dynamic properties of the cerebral metabolic rate of oxygen consumption (CMR(O2)) during changes in brain activity remain unclear. Therefore, the spatial and temporal evolution of functional increases in CMR(O2) was investigated in the rat somato-sensory cortex during forelimb stimulation under a suppressed blood flow response condition. Temporally, stimulation elicited a fast increase in tissue mitochondria CMR(O2) described by a time constant of ~1 second measured using flavoprotein autofluorescence imaging. CMR(O2)-driven changes in the tissue oxygen tension measured using an oxygen electrode and blood oxygenation measured using optical imaging of intrinsic signal followed; however, these changes were slow with time constants of ~5 and ~10 seconds, respectively. This slow change in CMR(O2)-driven blood oxygenation partly explains the commonly observed post stimulus blood oxygen level-dependent (BOLD) undershoot. Spatially, the changes in mitochondria CMR(O2) were similar to the changes in blood oxygenation. Finally, the increases in CMR(O2) were well correlated with the evoked multi-unit spiking activity. These findings show that dynamic CMR(O2) calculations made using only blood oxygenation data (e.g., BOLD functional magnetic resonance imaging (fMRI)) do not directly reflect the temporal changes in the tissue's mitochondria metabolic rate; however, the findings presented can bridge the gap between the changes in cellular oxidative rate and blood oxygenation. PMID- 22293986 TI - Importance of T lymphocytes in brain injury, immunodeficiency, and recovery after cerebral ischemia. AB - Following an ischemic stroke, T lymphocytes become activated, infiltrate the brain, and appear to release cytokines and reactive oxygen species to contribute to early inflammation and brain injury. However, some subsets of T lymphocytes may be beneficial even in the early stages after a stroke, and recent evidence suggests that T lymphocytes can also contribute to the repair and regeneration of the brain at later stages. In the hours to days after stroke, T-lymphocyte numbers are then reduced in the blood and in secondary lymphoid organs as part of a 'stroke-induced immunodeficiency syndrome,' which is mediated by hyperactivity of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, resulting in increased risk of infectious complications. Whether or not poststroke T-lymphocyte activation occurs via an antigen-independent process, as opposed to a classical antigen-dependent process, is still controversial. Although considerable recent progress has been made, a better understanding of the roles of the different T-lymphocyte subpopulations and their temporal profile of damage versus repair will help to clarify whether T-lymphocyte targeting may be a viable poststroke therapy for clinical use. PMID- 22293988 TI - Cellular prion protein participates in amyloid-beta transcytosis across the blood brain barrier. AB - The blood-brain barrier (BBB) facilitates amyloid-beta (Abeta) exchange between the blood and the brain. Here, we found that the cellular prion protein (PrP(c)), a putative receptor implicated in mediating Abeta neurotoxicity in Alzheimer's disease (AD), participates in Abeta transcytosis across the BBB. Using an in vitro BBB model, [(125)I]-Abeta(1-40) transcytosis was reduced by genetic knockout of PrP(c) or after addition of a competing PrP(c)-specific antibody. Furthermore, we provide evidence that PrP(c) is expressed in endothelial cells and, that monomeric Abeta(1-40) binds to PrP(c). These observations provide new mechanistic insights into the role of PrP(c) in AD. PMID- 22293990 TI - Evaluation of combination therapy in animal models of cerebral ischemia. AB - Combination therapy has been identified as a promising strategy to improve stroke management. We conducted a systematic review and meta-analysis of evidence from animal models of ischemic stroke to determine whether combining treatments improved efficacy. Multiple databases were searched and data were extracted from focal ischemia experiments comparing control groups, single treatments, and combination treatments. Of 11,430 papers identified, 142 met the inclusion criteria; these tested 126 treatments in 373 experiments using 8,037 animals (I(2)=85 to 96%). Taken together, single treatments reduced infarct size by 20% and improved neurological score by 12% compared with control; a second therapy improved efficacy by an additional 18% and 25%, respectively. Publication bias may affect combination efficacy for infarct size but not neurological score. Combining thrombolysis with other therapies may extend the time window from 4.4 to 8 hours in animal models, although testing beyond 6 hours is required to confirm this. Benefits of additional therapy decreased as the efficacy of the primary treatment increased, with combination efficacy reaching a ceiling at 60% to 80% protection. Combining treatments may bring benefits and extend the time window for treatment. More evidence is needed due to potential publication bias and heterogeneity. PMID- 22293989 TI - A critical appraisal of experimental intracerebral hemorrhage research. AB - The likelihood of translating therapeutic interventions for stroke rests on the quality of preclinical science. Given the limited success of putative treatments for ischemic stroke and the reasons put forth to explain it, we sought to determine whether such problems hamper progress for intracerebral hemorrhage (ICH). Approximately 10% to 20% of strokes result from an ICH, which results in considerable disability and high mortality. Several animal models reproduce ICH and its underlying pathophysiology, and these models have been widely used to evaluate treatments. As yet, however, none has successfully translated. In this review, we focus on rodent models of ICH, highlighting differences among them (e.g., pathophysiology), issues with experimental design and analysis, and choice of end points. A Pub Med search for experimental ICH (years: 2007 to 31 July 2011) found 121 papers. Of these, 84% tested neuroprotectants, 11% tested stem cell therapies, and 5% tested rehabilitation therapies. We reviewed these to examine study quality (e.g., use of blinding procedures) and choice of end points (e.g., behavioral testing). Not surprisingly, the problems that have plagued the ischemia field are also prevalent in ICH literature. Based on these data, several recommendations are put forth to facilitate progress in identifying effective treatments for ICH. PMID- 22293991 TI - Inhibition of neointimal hyperplasia with a novel zotarolimus coated balloon catheter. AB - BACKGROUND: Non stent based delivery of antiproliferative agents using drug coated balloon catheters may offer additional flexibility and efficacy in a broad range of applications. The lipophilic antiproliferative drug zotarolimus makes it a potential candidate for balloon delivery. The aim of the present study was to evaluate the safety and efficacy of a prototype zotarolimus coated balloon (ZCB) catheter in comparison to a zotarolimus eluting stent (ZES) in the porcine coronary overstretch model. METHODS: Eighty-four stents (diameters 3.0 and 3.5 mm; length 15 mm) were implanted in LAD and Cx of 42 domestic pigs: control (TriMaxx, Abbott, polymer coated stent without drug, implanted with uncoated PCI catheter, n = 56); ZES (ZoMaxx, Abbott, stent coated with zotarolimus in polymer, implanted with uncoated PCI catheter, n = 14); ZCB (TriMaxx, Abbott, polymer coated stent without drug, implanted with zotarolimus coated PCI catheter, n = 14). Drug content of the vessel wall (n = 9) was measured about 10-30 min post intervention with ZCB in additional pigs. RESULTS: Immediately after ZCB treatment 101 +/- 31 MUg of zotarolimus was detected in the coronary arteries. After 28 days ZES led to a reduction of neointimal area from 4.32 +/- 1.45 to 3.32 +/- 1.11 mm2 (P = 0.019 vs. control). The effect of neointimal inhibition was more pronounced with the novel ZCB (2.79 +/- 1.43 mm2, P = 0.001 vs. control). Inflammation score was significantly reduced in vessels treated with the ZCB (0.75 +/- 0.86 compared to control (1.45 +/- 0.94, P = 0.013) and ZES (1.65 +/- 0.90, P = 0.012). CONCLUSION: Zotarolimus coated balloons and stents were found to effectively reduce neointimal proliferation in the porcine coronary model. Inflammation scores were significantly reduced after treatment with the coated balloon. Zotarolimus balloon coating might be a novel option in preventing and treating restenosis. PMID- 22293992 TI - Acute streptococcal infection of the vulva. PMID- 22293993 TI - Carbon monoxide adsorption on neutral and cationic vanadium doped gold clusters. AB - The effect of a single vanadium dopant atom on the reactivity of small gold clusters is studied in the gas phase. In particular we investigated carbon monoxide adsorption on vanadium doped gold clusters using a low-pressure collision cell. Employing this technique the reactivity of both neutral and cationic clusters was studied under the same experimental conditions. Analysis of the kinetic data as a function of the pressure in the reaction cell shows that the reaction mechanism is composed of a fast adsorption and a delayed dissociation reaction. It is demonstrated that the reactivity of positively charged Au(n)V(m)(+) (n = 8-30, m = 0-3) is greatly enhanced as compared to the corresponding neutral species and that dissociation rates decrease with decreasing temperatures. While the overall magnitude of the reactivity does not change upon doping with vanadium clusters, the size dependence is significantly affected. The neutral singly vanadium doped gold clusters show a sudden drop after size Au(13)V, followed by a smooth increase, in contrast to the extended odd-even staggering for bare gold clusters. This difference can be explained by changes in the electronic structure of the clusters, related to the partly filled 3d shell of the vanadium dopant atom. PMID- 22293994 TI - Influence of a 50 Hz magnetic field and of all-trans-retinol on the proliferation of human cancer cell lines. AB - In vitro exposure to power frequency magnetic fields (MF) has been reported to influence cell proliferation and differentiation. However, the nature of the response of different human cancer cell types to these fields has not been sufficiently characterized. The present work investigates the response of two proliferating human cell lines of neuroblastoma (NB69) and hepatocarcinoma (HepG2) to a 42 h, intermittent treatment with a weak, 100 uT, 50 Hz MF, alone or in combination with 0.5 uM all-trans-retinol (ROL), a retinoid currently applied in oncostatic therapies. In each experimental replicate the cell samples were submitted to one of the following treatment combinations: MF+/ROL+, MF+/ROL-, MF /ROL+ or MF-/ROL-. The proliferative response was determined by cell counting (Trypan blue exclusion), BrdU incorporation and by spectrophotometric analysis of total protein and DNA content. The results show that when administered separately, the two treatments, MF and ROL, significantly enhanced cell proliferation in both cell lines. In NB69 simultaneous administration of MF and ROL induced an additive effect on cell proliferation, associated to increased DNA content. By contrast, in HepG2 the ROL-induced cell proliferation and increased protein content were partially blocked by simultaneous exposure to MF. Taken together, these data show that both agents, a weak MF and ROL at a low concentration, induce proliferative responses in the two assayed human cell lines. However, significant differences were observed between the responses of the two cellular species to the combined treatment with ROL and MF, indicating that the mechanisms underlying the cellular response to each of the two agents can mutually interact in a manner that is cell type-specific. PMID- 22293995 TI - A highly active and magnetically retrievable nanoferrite-DOPA-copper catalyst for the coupling of thiophenols with aryl halides. AB - Diaryl sulfides were synthesized using a magnetically recoverable heterogeneous Cu catalyst via one-pot multi component reaction using MW irradiation; the use of isopropanol as a benign reaction medium, easy recovery of the catalyst using an external magnet, efficient recycling, and the high stability of the catalyst render the protocol economic and sustainable. PMID- 22293996 TI - Effective monitoring of agriculture: a response. AB - The development of effective agricultural monitoring networks is essential to track, anticipate and manage changes in the social, economic and environmental aspects of agriculture. We welcome the perspective of Lindenmayer and Likens (J. Environ. Monit., 2011, 13, 1559) as published in the Journal of Environmental Monitoring on our earlier paper, "Monitoring the World's Agriculture" (Sachs et al., Nature, 2010, 466, 558-560). In this response, we address their three main critiques labeled as 'the passive approach', 'the problem with uniform metrics' and 'the problem with composite metrics'. We expand on specific research questions at the core of the network design, on the distinction between key universal and site-specific metrics to detect change over time and across scales, and on the need for composite metrics in decision-making. We believe that simultaneously measuring indicators of the three pillars of sustainability (environmentally sound, social responsible and economically viable) in an effectively integrated monitoring system will ultimately allow scientists and land managers alike to find solutions to the most pressing problems facing global food security. PMID- 22293997 TI - The global role of kidney transplantation. AB - World Kidney Day on March 8th 2012 provides a chance to reflect on the success of kidney transplantation as a therapy for end stage kidney disease that surpasses dialysis treatments both for the quality and quantity of life that it provides and for its cost effectiveness. Anything that is both cheaper and better, but is not actually the dominant therapy, must have other drawbacks that prevent replacement of all dialysis treatment by transplantation. The barriers to universal transplantation as the therapy for end stage kidney disease include the economic limitations which, in some countries place transplantation, appropriately, at a lower priority than public health fundamentals such as clean water, sanitation and vaccination. Even in high income countries the technical challenges of surgery and the consequences of immunosuppression restrict the number of suitable recipients, but the major finite restrictions on kidney transplantation rates are the shortage of donated organs and the limited medical, surgical and nursing workforces with the required expertise. These problems have solutions which involve the full range of societal, professional, governmental and political environments. World Kidney Day is a call to deliver transplantation therapy to the one million people a year who have a right to benefit. PMID- 22293998 TI - Carotid ultrasound for the early diagnosis of atherosclerosis in chronic kidney disease. PMID- 22293999 TI - Longitudinal observational studies and causality. PMID- 22294000 TI - The value of serum free light chain assay in patients with monoclonal gammopathies and renal failure. PMID- 22294001 TI - Renal supportive care and palliative care: revision and proposal in kidney replacement therapy. AB - Patients with chronic kidney disease may receive sustained renal supportive care and renal palliative care (RPC) starting with the diagnosis of the disease, throughout the various stages of renal replacement therapy (RRT), the cessation of the RRT, and in the decision of whether to provide conservative treatment or non-initiation of RRT. This article reviews the literature on the development of renal palliative care and proposed RPC models. We describe the progression of disease in organ failure, which is very different from other areas of palliative care (PC). We describe important components of resident nephrology training in PC. We discuss the management of pain and symptom control, as well as communication skills and other psychological and ethical aspects in the renal patient. We conclude that in chronic renal patients, a palliative care approach can provide a positive impact on the quality of life of patients and their families, as well as optimizing the complex treatment of the renal patient. PMID- 22294002 TI - Start-up of a clinical sample processing, storage and management platform: organisation and development of the REDinREN Biobank. AB - BACKGROUND: The creation of the Biobank, a resource pertaining to the Spanish Renal Research Network (REDinREN) promotes advances in clinical research on kidney disease in Spain. The Biobank's aims are to generate an archive of clinical samples and associated data, furnish those samples to research teams, and coordinate with European biobanks. METHOD: Applicable legislation had to be complied with in order to launch the Biobank project (Biomedical Research Law, Data Protection Law and Biological Sample Transport Regulations). A strict work protocol and a new database for the Network's clinical data were also implemented. RESULTS: Over time, the Biobank has acquired additional infrastructure and qualified personnel. In 2010, 2953 new patient samples were collected, giving a total of 37,043 stored vials containing different types of samples. Furthermore, the Biobank is currently participating in eleven research projects. DISCUSSION: Although the Biobank was originally designed for REDinREN use, we must take joint action to make this biological sample storage system and the many possibilities it offers available to the entire nephrological community with a view to promoting kidney disease research. PMID- 22294003 TI - Haemodialysis using high cut-off dialysers for treating acute renal failure in multiple myeloma. AB - INTRODUCTION: Acute renal failure (ARF) occurs in 12%-20% of all multiple myeloma (MM) cases, and the survival of these patients depends on renal function recovery. Renal function is not recovered in 75% of dialysis-dependent patients, and their mean survival with replacement therapy is less than one year. Renal tubular disease is the most frequent cause of renal failure. It is present in more than 55% of renal failure cases and in 75% of those requiring dialysis. Rapid reduction of free light chain levels in the blood is necessary in order to recover renal function. One coadjuvant measure in treating the disease is reducing light chain levels with plasmapheresis, but its efficacy has not yet been clearly proven. Our proposal was therefore to use extended haemodialysis sessions with high cut-off dialysers (HCO-HD), obtaining a recovery rate of more than 60%. We present the progress of 6 patients with myeloma and acute renal failure who were treated with HCO-HD and the complications associated with using this type of haemodialysis. Then, we review the pros and cons of this technique. METHOD: Six patients diagnosed with MM and ARF requiring dialysis and with serum free light chain levels above 500 mg/l were treated with 8-hour haemodialysis sessions with an HCO-HD filter. Before and after each session, serum free light chain levels were measured by nephelometry; other parameters were recorded as well. At the same time, patients underwent chemotherapy according to protocols. RESULTS: The symptom onset times of the 3 men and 3 women diagnosed with MM and ARF were highly variable, from 7 days to more than 1 year. We performed 90 extended sessions with HCO-HD filters, and each patient underwent between 6 and 40 sessions. Free light chain levels decreased by a mean of 65% between treatment onset and completion, except in one patient who experienced a 12.6% reduction. The mean percentage of reduction of light chain levels per session was 54.98% +/- 17.27%. A complication occurred during 28% of the sessions. Of these complications, 48% were due to system coagulation. There were no major changes in pre-dialysis albumin, calcium, phosphorous or magnesium levels, although lower values that were not clinically relevant were recorded in one case. Renal function was recovered in 3 patients, they are alive and dialysis-free. In biopsied cases that recovered renal function, the specimen showed tubular nephropathy only. Those patients who took longer to be diagnosed did not recover their renal function, and when biopsied, they were diagnosed with renal tubular disease and light chain deposition disease. CONCLUSION: We found extended haemodialysis with HCO-HD filters to be a reasonable alternative in ARF caused by renal tubular disease, and achieved a recovery rate of 50% in our cases. Function recovery was influenced by the elapsed time between symptom onset and myeloma diagnosis, histological findings, promptness of starting chemotherapy, response to chemotherapy, and effectiveness of light chain extraction. In any case, further studies are needed to examine new chemotherapy agents and new direct free light chain removal techniques. PMID- 22294004 TI - Early detection of chronic kidney disease: collaboration of Belgrade nephrologists and primary care physicians. AB - BACKGROUND: Belgrade screening study was undertaken in order to detect persons with CKD markers in at risk populations and to educate primary care physicians how to carry out CKD screening. METHODS: The study was performed by primary care physicians from thirteen Belgrade health centers in collaboration with nephrologists from clinical centers. Subjects without previously known kidney disease were enrolled: 1316 patients with hypertension without diabetes, 208 patients with type 2 diabetes and 93 subjects older than 60 years without hypertension or diabetes. The survey consisted of an interview, consisted of an interview, estimation of glomerular filtration rate (eGFR-MDRD), single urine dipstick detection of proteinuria, hematuria, glucosuria, microalbuminuria. RESULTS: Microalbuminuria with or without proteinuria in combination with eGFR>60 ml/min/1.73 m2 was detected in 17% , 41% and 24% of patients with hypertension, diabetes and those above 60 years, respectively. Reduced eGFR (<60 ml/min/1.73 m2 ) was found in 23%, 12% and 22% of the same patient groups. The prevalence of CKD markers increased with increasing number of risk factors. CONCLUSION: High prevalence of CKD markers in at risk population detected by primary care physicians in this collaborative study seems to be the best way to encourage primary care physicians to carry out regular CKD screening. PMID- 22294005 TI - Serum uric acid as a marker of all-cause mortality in an elderly patient cohort. AB - INTRODUCTION: There is growing evidence of the role of serum uric acid (SUA) as a risk factor for cardiovascular and renal disease. We analysed the association between baseline SUA and overall mortality in a cohort of elderly patients followed prospectively for 5 years. PATIENTS AND METHODS: Eighty clinically stable patients, median age 83 years (range 69-97), 31.3% men, 35% diabetics, 83% hypertensives were randomly recruited at Geriatrics and Nephrology visits between January and April 2006 and followed for 5 years. We measured baseline SUA and serum creatinine and estimated glomerular filtration rate (GFR) with MDRD abbreviated. In Nephrology Department patients, we measured proteinuria in 24 hour urine and in Geriatrics department patients we measured proteinuria (mg/dl)/creatinine (mg/dl) in urine (first morning urine). Predictive variables were: baseline SUA and plasma creatinine; estimated GFR (abbreviated MDRD formula); and we recorded age, gender, baseline comorbidity (Charlson index), individualised cardiovascular treatment and mortality. STATISTICAL ANALYSIS: SPSS15.0. RESULTS: baseline SUA was normally distributed and its median was 5.85 mg/dl. We found no significant differences in levels of SUA by gender, history of diabetes mellitus, hypertension, diuretic drug use, heart disease, peripheral arterial disease or stroke. Patients with a history of heart failure had significantly higher SUA (7.00 +/- 1.74 vs 5.90 +/- 1.71, P=.031). Some 41 deaths occurred during follow-up (15 men and 26 women): 15 due to general deterioration, 8 due to infections, 4 due to stroke, 4 due to tumours, 3 due to cardiovascular disease, 2 due to complications of fractures and 5 due to unknown causes. Patients with SUA higher than the median had significantly lower GFR and higher mortality at 5 years. In the Cox analysis for overall mortality [independent variables: age, gender, Charlson Index, history of heart failure, SUA, creatinine, proteinuria and GFR (MDRD)] only SUA levels (HR: 1.35; 1.17-1.56 P=.000) were independently associated with mortality. CONCLUSIONS: In our study, levels of SUA are an independent risk factor for mortality in elderly patients. PMID- 22294006 TI - The lack of income is associated with reduced survival in chronic haemodialysis. AB - INTRODUCTION: Poor socioeconomic status in the patient population is one of the causes of the lack of primary and secondary prevention of chronic kidney disease and negatively affects the survival of patients on chronic haemodialysis (HD). OBJECTIVE: To confirm whether the low or absent income of the incident population on HD is a factor of poor prognosis. METHODS: We used the incident HD population of the Argentine Registry of Chronic Dialysis. Follow-up lasted 12 months, performing an intention to treat analysis. We applied the Cox model to assess the association between income and survival of patients after adjusting for age, sex, diabetes, comorbidities, initial laboratory results, and first vascular access. RESULTS: We analysed 13466 adult patients (age at onset: 60.4 +/- 15.6 years; 57.2% were male, and 39.2% diabetic) who were assigned to 2 groups: 1) "no income" group, 5661 patients (age at onset: 60.3 +/- 15.4 years; 53.1% were male and 41.4% diabetic), 2) "with income" group, 7805 patients (age at onset, 60.5 +/ 15-8] years; 60.1% were male and 37.5% diabetic). The "no income" group had a hazard ratio of 1.19 (95% confidence interval [CI]: 1.11-1.28) in the univariate analysis, 1.23 (95% CI: 1.14-1.32 ) considering age and gender, 1.22 (95% CI: 1.13-1.31) by adding diabetes mellitus, 1.26 (95% CI: 1.18-1.36) by adding comorbidities, 1.25 (95% CI: 1.16- 1.35) by adding the initial laboratory results, and 1.24 (95% CI: 1.15- 1.33) if temporary vascular access is included. All models resulted in a significance of P=.000. CONCLUSIONS: Low or no income of patients at the time of entry into HD is an independent risk factor for immediate lower survival. PMID- 22294007 TI - Effect of intranasal DDAVP in prevention of hypotension during hemodialysis. AB - INTRODUCTION: The development of intradialytic hypotension during hemodialysis (HD) in which fluid removal is the primary goal, contributes to the excessive morbidity that is associated with the dialysis procedure. MATERIALS AND METHODS: In a double blinded clinical trial, we compared the possible effect of intranasal DDAVP with intranasal distilled water as a placebo in prevention of intradialytic hypotension (IDH) in patients with known symptomatic IDH. In the first month of the study, nasal spray of distill water were administrated 30 minutes before all HD session (Placebo Group, Group 1) and then after a 30-day washout period we were used intranasal DDAVP 30 minutes before HD session (Vasopressin Group, Group 2). Blood pressure was measured just before HD, two hours later and after termination of HD. A hypotensive episode was defined as a decline of systolic blood pressure of more than 10mm Hg. RESULTS: In overall Seventeen patients (nine men, eight women; mean age, 47.5 years) with known symptomatic IDH were enrolled in the study. The kind of dialysis membranes, mean of blood flow rate, dialyzate flow rate and ultrafiltration rate were the same in both groups. Each group has 204 HD session (17 * 12). Hypotensive episode occurred 18 times (8.82%) in vasopressin group compared with 125 times (61.27%) in placebo group and there was a significant association between them (p=0.0001). In addition mean arterial blood pressure in vasopressin group was 80.77 and in placebo group was 73.92 and also there was a significant association (p=0.0001). The mean Kt/v in group 1 and 2 were 1.29 and 1.28 without any differences between them (p=0.896). CONCLUSION: These results indicate that Compared with placebo, Vasopressin is significantly associated with a decreased incidence of intradialytic hypotension episodes during hemodialysis. PMID- 22294008 TI - Vascular accesses in haemodialysis: a challenge to be met. AB - BACKGROUND: Chronic kidney disease is a leading problem in public health due to its high incidence, prevalence and high morbidity and mortality, especially for those who require renal replacement therapy (RRT). As has already been described by other authors, the vascular access is one of the factors determining morbidity and mortality of patients in haemodialysis as well as their complications, which incur a high cost. OBJECTIVES: To know the real situation of our clinical practice, compare it with data from other studies, and to measure the degree of compliance by these patients with the recommendations of haemodialysis (HD) Clinical Practice Guidelines regarding vascular access . Also, to assess survival according to the type of vascular access used, adjusting for comorbidity factors. PATIENTS AND METHODS: We studied the vascular access of our prevalent patients on haemodialysis by October 2009 (n=299, 62% men). Of these, 64% underwent HD through an autologous arteriovenous fistula (AVF), 3% were carrying synthetic grafts, and 33% had a central venous catheter (CVC). These percentages do not comply with the recommendations of the S.E.N. and KDOQI clinical guidelines. In order to know the real situation of our clinical practice, we compared our data with other studies, and measured the degree of compliance with the recommendations of the guidelines. The incident patients on HD were studied from January 2004 to October 2009 (n=422). We analysed basal nephropathy, associated diseases, and the type of vascular access at the start of HD. RESULTS: A total of 30% had an AVF, 1% had synthetic grafts, and 69% had CVC. The calculated relative risk (RR) of death associated with the use of CVC at the start of HD was 3.68 (95% CI: 2.93-6.35) adjusted for other factors of comorbidity (age, diabetes mellitus, ischaemic heart disease, peripheral arterial disease). CONCLUSIONS: The high mortality associated at the beginning of HD with CVC (RR: 3.68), independently of other factors, make the decrease in the use of this vascular access an objective of first order. Presently, we have not been able to meet the objectives from the different Clinical Guidelines with respect to the prevalence and incidence of the vascular accesses for HD. PMID- 22294009 TI - Changes in body composition parameters in patients on haemodialysis and peritoneal dialysis. AB - INTRODUCTION: Proper hydration is one of the major aims in haemodialysis (HD) and peritoneal dialysis (PD). Bioimpedance spectroscopy appears to be a promising method for the evaluation and follow up of the hydration status in dialysis patients (P). OBJECTIVES: We compared body composition between stable patients on HD and PD after six months. PATIENTS AND METHOD: An observational study with 62 P on HD and 19 P on PD was performed. Clinical, biochemical and bioimpedance parameters were analysed. RESULTS: In the comparative study, PD P were younger (50 +/- 10 vs 57 +/- 14 years, P=.031). The Charlson Comorbidity Index (4.8 +/- 3 vs 7.5 +/- 3, P<.001), time on dialysis (16.9 +/- 18.01 vs 51.88 +/- 68.79 months, P=.020) and C-Reactive Protein [3 (3-9.3) vs 5.25 (1-76.4)] were lower. Total protein levels (7.46 +/- 0.44 vs 7.04 +/- 0.55 g/dl, P=.005) and transferrin levels (205 +/- 41 vs 185 +/- 29 mg/dl, P=.024) were higher. BIS: Intracellular water (19.67 +/- 3.61 vs 16.51 +/- 3.36 litres, P=.010), lean tissue mass (LTM) (37.20 +/- 8.65 vs 32.57 +/- 8.72 kg, P=.029), total cellular mass (TCM) (20.53 +/- 5.65 vs 17.56 +/- 5.91 kg, P=.033), and bioelectrical impedance phase angle (Phi 50) (5.81 +/- 0.86 vs 4.74 +/- 0.98, P=.000) were higher than in HD P. Overhydration: 22% in HD y 10% in PD, in conditions referred to in methods. Six months later, PD P increased in weight (73.75 +/- 12.27 vs 75.22 +/- 11.87 kg, P=.027), total fat (FAT) (26.88 +/- 10 vs 30.02 +/- 10 kg, P=.011) and relative fat (Rel FAT) (35.75 +/- 9.87 vs 39.34 +/- 9.12, P=.010); and decreased in ICW (18.56 +/- 3.45 vs 17.65 +/- 3.69 l, P=.009), LTM (36.95 +/- 8.88 vs 34 +/- 9.70 kg, P=.008) and relative LTM (Rel LTM) (50.85 +/- 12.33 vs 45.40 +/- 11.95%, P=.012). In the multivariate analysis, weight variation (?) was related to ? FAT (P < .001). We found a correlation between fat increase and lean tissue mass decrease. Six months later, in HD P, we observed a reduction in ECW (15.11 +/- 2.45 vs 14.00 +/- 2.45, P.001), without changes in other parameters. CONCLUSIONS: Bioelectrical impedance analysis facilitates the assessment of changes in body composition so as to correct dry weight and to introduce changes in treatment schedule.. PMID- 22294010 TI - The role of interleukin 6 in the pathogenesis of hyponatremia associated with Guillain-Barre syndrome. PMID- 22294011 TI - Estimating glomerular filtration rate in order to adjust drug doses: confusion abounds. PMID- 22294012 TI - Is peripheral and/or catheter blood necessary for performing haemoculture in haemodialysis patients whose central venous catheter presents bacteraemia? PMID- 22294013 TI - Economic impact of estimating renal function in patients with systemic lupus erythematosus. PMID- 22294014 TI - Adrenal myelolipoma associated with primary hyperaldosteronism. PMID- 22294015 TI - Chronic kidney disease in the elderly: the impact of patients' sex. PMID- 22294016 TI - Reactive haemophagocytic syndrome associated with parvovirus B19 in a kidney pancreas transplant patient. PMID- 22294017 TI - Rhabdomyolysis and acute renal failure following hard physical activity in a patient treated with rosuvastatin. PMID- 22294018 TI - Emphysematous cystitis resolved with medical treatment. A case report and literature review. PMID- 22294019 TI - Intestinal pseudo-obstruction secondary to persistent constipation due to lanthanum carbonate. PMID- 22294020 TI - Acute renal failure due to gabapentin. A case report and literature. PMID- 22294021 TI - Haemorrhagic fever with renal failure syndrome: a case report. PMID- 22294022 TI - Aciclovir and valaciclovir neurotoxicity in patients with renal failure. PMID- 22294023 TI - Serial ultrasound of the vascular access. PMID- 22294024 TI - Cilostazol induces cellular senescence and confers resistance to etoposide induced apoptosis in articular chondrocytes. AB - We recently reported that cilostazol protects chondrocytes against stress-induced apoptosis and prevents cartilage destruction in an osteoarthritis (OA) model. In the present study, we elucidate the mechanism underlying the protective effect induced by cilostazol against stress-induced apoptosis in chondrocytes. Cilostazol significantly reduced the expression of type II collagen and stimulated the accumulation of beta-catenin in primary rat articular chondrocytes. Moreover, cilostazol-induced chondrocytes showed induction of senescent phenotypes, such as changes in cell morphology, decrease in cell proliferation and increase in specific senescence-associated beta-galactosidase (SA-beta-gal) staining. Moreover, dedifferentiated chondrocytes obtained by serial subculture showed cellular senescence that increased with passage number. In addition, the percentage of terminal dUTP nick end-labeling (TUNEL)-positive cells was higher when chondrocytes were treated with cilostazol and the apoptosis inducer etoposide than when the cells were treated with etoposide alone. Our findings suggest that cilostazol induces dedifferentiation and senescence in rat articular chondrocytes and renders them resistant to etoposide-induced apoptosis. PMID- 22294025 TI - gamma-Lactones from delta-lactones: total synthesis of the biosynthetic derailment product mupirocin H. AB - Two different strategies for the synthesis of functionalised gamma-lactones from delta-lactones are described and used in a convergent synthesis of (+)-mupirocin H. The total synthesis is versatile and may be readily adapted for the preparation of further truncated metabolites from Pseudomonas fluorescens. PMID- 22294026 TI - Motor imagery of tool use: relationship to actual use and adherence to Fitts' law across tasks. AB - A Fitts' task was used to investigate how tools are incorporated into the internal representations that underlie pointing movements, and whether such knowledge can be generalized across tasks. We measured the speed-accuracy trade offs that occurred as target width was varied for both real and imagined movements. The dynamics of the pointing tool used in the task were manipulated- regular pen, top-heavy tool, and bottom-heavy tool--to test the fidelity of internal representations of movements involving the use of novel tools. To test if such representations can be generalized, the orientation of the pointing task was also manipulated (horizontal vs. vertical). In all conditions, both real and imagined performances conformed to the speed-accuracy relationship described by Fitts' law. We found significant differences in imagined MTs for the two weighted tools compared to the regular pen, but not between the weighted tools. By contrast, real movement durations differed between all tools. These results indicate that even relatively brief experience using novel tools is sufficient to influence the internal representation of the dynamics of the tool-limb system. However, in the absence of feedback, these representations do not make explicit differences in performances resulting from the unique dynamics of these weighted tools. PMID- 22294027 TI - Assembling an ant community: species functional traits reflect environmental filtering. AB - Species should only persist in local communities if they have functional traits that are compatible with habitat-specific environmental conditions. Consequently, pronounced regional environmental gradients should produce environmental filtering, or a trait-based spatial segregation of species. It is critical to quantify the links between species' functional traits and their environment in order to reveal the relative importance of this process to community assembly and promote understanding of the impacts of ongoing environmental changes. We investigated this relationship using epigaeic ants in an environmentally heterogeneous region of Florida. We found evidence for environmental filtering as environmental conditions such as groundcover, surface temperature, vapor pressure deficit, and plant diversity were strongly correlated with assemblage composition. Certain species traits appeared particularly important to persistence: (1) ants in environments with less groundcover have relatively longer legs but do not differ in size, (2) ants in hotter environments exhibit greater thermal tolerances, and (3) ants in hotter and drier environments do not exhibit greater desiccation resistance. These findings show surface complexity and temperature may interact with morphology and physiology to impact the spatial distribution of ants and underscore the importance of climate change. Climate warming is predicted to alter assemblage composition, competitive dynamics, and consequently impact ecosystem processes. We suggest environmental filters acting at regional scales, as shown here, act in tandem with more frequently studied local-scale competitive interactions to delimit ant community assemblages. PMID- 22294028 TI - Variation in foliar nitrogen and albedo in response to nitrogen fertilization and elevated CO2. AB - Foliar nitrogen has been shown to be positively correlated with midsummer canopy albedo and canopy near infrared (NIR) reflectance over a broad range of plant functional types (e.g., forests, grasslands, and agricultural lands). To date, the mechanism(s) driving the nitrogen-albedo relationship have not been established, and it is unknown whether factors affecting nitrogen availability will also influence albedo. To address these questions, we examined variation in foliar nitrogen in relation to leaf spectral properties, leaf mass per unit area, and leaf water content for three deciduous species subjected to either nitrogen (Harvard Forest, MA, and Oak Ridge, TN) or CO(2) fertilization (Oak Ridge, TN). At Oak Ridge, we also obtained canopy reflectance data from the airborne visible/infrared imaging spectrometer (AVIRIS) to examine whether canopy-level spectral responses were consistent with leaf-level results. At the leaf level, results showed no differences in reflectance or transmittance between CO(2) or nitrogen treatments, despite significant changes in foliar nitrogen. Contrary to our expectations, there was a significant, but negative, relationship between foliar nitrogen and leaf albedo, a relationship that held for both full spectrum leaf albedo as well as leaf albedo in the NIR region alone. In contrast, remote sensing data indicated an increase in canopy NIR reflectance with nitrogen fertilization. Collectively, these results suggest that altered nitrogen availability can affect canopy albedo, albeit by mechanisms that involve canopy level processes rather than changes in leaf-level reflectance. PMID- 22294029 TI - Sparse color interest points for image retrieval and object categorization. AB - Interest point detection is an important research area in the field of image processing and computer vision. In particular, image retrieval and object categorization heavily rely on interest point detection from which local image descriptors are computed for image matching. In general, interest points are based on luminance, and color has been largely ignored. However, the use of color increases the distinctiveness of interest points. The use of color may therefore provide selective search reducing the total number of interest points used for image matching. This paper proposes color interest points for sparse image representation. To reduce the sensitivity to varying imaging conditions, light invariant interest points are introduced. Color statistics based on occurrence probability lead to color boosted points, which are obtained through saliency based feature selection. Furthermore, a principal component analysis-based scale selection method is proposed, which gives a robust scale estimation per interest point. From large-scale experiments, it is shown that the proposed color interest point detector has higher repeatability than a luminance-based one. Furthermore, in the context of image retrieval, a reduced and predictable number of color features show an increase in performance compared to state-of-the-art interest points. Finally, in the context of object recognition, for the Pascal VOC 2007 challenge, our method gives comparable performance to state-of-the-art methods using only a small fraction of the features, reducing the computing time considerably. PMID- 22294030 TI - Nonlinear approach for enhancement of image focus volume in shape from focus. AB - Mostly, shape-from-focus algorithms use local averaging using a fixed rectangle window to enhance the initial focus volume. In this linear filtering, the window size affects the accuracy of the depth map. A small window is unable to suppress the noise properly, whereas a large window oversmoothes the object shape. Moreover, the use of any window size smoothes focus values uniformly. Consequently, an erroneous depth map is obtained. In this paper, we suggest the use of iterative 3-D anisotropic nonlinear diffusion filtering (ANDF) to enhance the image focus volume. In contrast to linear filtering, ANDF utilizes the local structure of the focus values to suppress the noise while preserving edges. The proposed scheme is tested using image sequences of synthetic and real objects, and results have demonstrated its effectiveness. PMID- 22294031 TI - Groupwise registration of multimodal images by an efficient joint entropy minimization scheme. AB - Groupwise registration is concerned with bringing a group of images into the best spatial alignment. If images in the group are from different modalities, then the intensity correspondences across the images can be modeled by the joint density function (JDF) of the cooccurring image intensities. We propose a so-called treecode registration method for groupwise alignment of multimodal images that uses a hierarchical intensity-space subdivision scheme through which an efficient yet sufficiently accurate estimation of the (high-dimensional) JDF based on the Parzen kernel method is computed. To simultaneously align a group of images, a gradient-based joint entropy minimization was employed that also uses the same hierarchical intensity-space subdivision scheme. If the Hilbert kernel is used for the JDF estimation, then the treecode method requires no data-dependent bandwidth selection and is thus fully automatic. The treecode method was compared with the ensemble clustering (EC) method on four different publicly available multimodal image data sets and on a synthetic monomodal image data set. The obtained results indicate that the treecode method has similar and, for two data sets, even superior performances compared to the EC method in terms of registration error and success rate. The obtained good registration performances can be mostly attributed to the sufficiently accurate estimation of the JDF, which is computed through the hierarchical intensity-space subdivision scheme, that captures all the important features needed to detect the correct intensity correspondences across a multimodal group of images undergoing registration. PMID- 22294032 TI - Hierarchical oriented predictions for resolution scalable lossless and near lossless compression of CT and MRI biomedical images. AB - We propose a new hierarchical approach to resolution scalable lossless and near lossless (NLS) compression. It combines the adaptability of DPCM schemes with new hierarchical oriented predictors to provide resolution scalability with better compression performances than the usual hierarchical interpolation predictor or the wavelet transform. Because the proposed hierarchical oriented prediction (HOP) is not really efficient on smooth images, we also introduce new predictors, which are dynamically optimized using a least-square criterion. Lossless compression results, which are obtained on a large-scale medical image database, are more than 4% better on CTs and 9% better on MRIs than resolution scalable JPEG-2000 (J2K) and close to nonscalable CALIC. The HOP algorithm is also well suited for NLS compression, providing an interesting rate-distortion tradeoff compared with JPEG-LS and equivalent or a better PSNR than J2K for a high bit rate on noisy (native) medical images. PMID- 22294033 TI - H.264/SVC mode decision based on optimal stopping theory. AB - Fast mode decision algorithms have been widely used in the video encoder implementation to reduce encoding complexity yet without much sacrifice in the coding performance. Optimal stopping theory, which addresses early termination for a generic class of decision problems, is adopted in this paper to achieve fast mode decision for the H.264/Scalable Video Coding standard. A constrained model is developed with optimal stopping, and the solutions to this model are employed to initialize the candidate mode list and predict the early termination. Comprehensive simulation results are conducted to demonstrate that the proposed method strikes a good balance between low encoding complexity and high coding efficiency. PMID- 22294034 TI - Antitumor effects of oncolytic adenovirus armed with Drosophila melanogaster deoxyribonucleoside kinase in colorectal cancer. AB - Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (Dm-dNK) was applied as a cancer gene therapeutic approach. To improve the antitumor effect of Dm-dNK, a novel suicide gene system based on an oncolytic adenovirus vector was developed to produce therapeutic effects towards colorectal cancer cells. We constructed an oncolytic adenoviral vector (ZD55), which was designed by deletion of the E1B-55 kDa gene for selective replication in tumor cells, containing suicide gene (Dm-dNK) driven by a cytomegalovirus promoter. We analysed the expression and activity of Dm-dNK in colorectal cancer cells (HCT-116 and SW620) via reverse transcription (RT)-PCR and enzyme assay. We assessed selective cytotoxic effects of Dm-dNK with the presence of the analogs (E)-5-(2-bromovinyl) 2'-deoxyuridine (BVDU), difluorodeoxycytidine (dFdC) or 1-beta-D arabinofuranosylthymine (ara-T) by MTT and FACS; the variation of oncolytic adenovirus was detected by titer assay and western blot analysis. Our data showed that ZD55-Dm-dNK mediated high expression of Dm-dNK in HCT-116 and SW620 cancer cell lines and low levels of expression in WI-38 and MRC-5 normal cells, strong cytotoxicity was observed only in tumor cells after ZD55-Dm-dNK infection combined with nucleoside analogs (NA). When ZD55-Dm-dNK was combined with BVDU or dFdC, it produced a synergistic inhibitive effect of adenovirus replication while maintaining specific cancer cell killing activity. The results suggest that the novel oncolytic virus ZD55-Dm-dNK, in combination with NA, has potential as an efficient selective antitumoral agent and may produce synergistic effects in safe control of adenovirus, which is a new promising therapeutic for colorectal cancer. PMID- 22294035 TI - Direct aerobic photo-oxidative syntheses of aromatic methyl esters from methyl aromatics using anthraquinone-2,3-dicarboxylic acid as organophotocatalyst. AB - This paper reports a useful method for facile direct syntheses of aromatic methyl esters from methyl aromatics by aerobic photo-oxidation using anthraquinone-2,3 dicarboxylic acid as an organophotocatalyst. PMID- 22294036 TI - Chemoembolization of unresectable hepatocellular carcinoma: Decreased toxicity with slow-release doxorubicin-eluting beads compared with lipiodol. AB - Chemoembolization with lipiodol (TACE) improves survival of selected patients with unresectable hepatocellular carcinoma (HCC), but results in substantial toxicity. To improve treatment tolerance, we conducted this phase II study using doxorubicin-loaded beads (DC Beads(r)) delivered by selective transcatheter arterial chemoembolization (DEB-TACE). We compared the results with those obtained with TACE in our historical controls. Thirty-five patients were recruited with diagnoses of HCC. Patients received DEB-TACE with doxorubicin loaded on DC Beads. Computed tomography of the upper abdomen was performed one month after DEB-TACE. Historical controls were a group of 70 patients with matched characteristics treated with TACE. After a median follow-up of 14.1 months (range, 6-36 months), 22 patients (63%) had an objective response. There was a statistically significant decrease in liver enzymes (p<0.001), lactate dehydrogenase, (p<0.001) in DEB-TACE-treated patients compared to TACE-treated patients. DEB-TACE with doxorubicin-loaded DC Beads, a safe and reliable treatment for HCC, leads to decreased toxicity compared to TACE. PMID- 22294038 TI - An all-purpose building block: B12N12 fullerene. AB - We have theoretically shown that the boron nitride fullerene cage B(12)N(12) is an all-purpose building block for fabricating multifarious BN nanotubes. Firstly, we investigated the stability and structural of the boron nitride fullerene cage B(12)N(12) and the polymerized derivatives obtained from it. Interestingly we found out that two B(12)N(12) cages can spontaneously form one BN nanotube with two closed ends through the structural transformation when one cage meets another. These results indicated that the fullerene B(12)N(12) can be polymerized to build various remarkable polymers through the spontaneous structural transformation when they are together, which all have planer or tridimensional shapes with a hollow tubular structure, even at the juncture of the coalesced B(12)N(12). Simultaneously, after the structure optimization, the quadrangles at the juncture of the coalesced B(12)N(12) disappear to form a perfect surface only composed of hexagons. Then, we calculated the energy of all the considered nanostructures. The polymerization of the fullerene B(12)N(12) is exothermic and thus can form very stable derivative polymers. These theoretical conclusions stimulate us to use the fullerene B(12)N(12) as an all-purpose building block to construct various BN nanostructures for purpose of fundamental research and potential applications. PMID- 22294037 TI - Nocodazole increases the ERK activity to enhance MKP-1expression which inhibits p38 activation induced by TNF-alpha. AB - The mitogen-activated protein kinase p38 plays key roles in cell progression, differentiation, inflammation, and apoptosis. p38 is activated by a variety of extracellular stimuli such as UV and proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha). It has been demonstrated that destruction of microtubules with different reagents led to impaired p38 activation in response to various extracellular stimuli. However, several other groups have reported that microtubule-interfering agents stimulate the activation of MAPK superfamily members including p38 in certain cell context. The discrepancy suggests that destruction of microtubules stimulates the activation of MAPK superfamily members and thereby induces certain feedback inhibitor(s) of p38 signaling. In this article, we report that nocodazole, a widely used microtubule-interfering agent, antagonized UV- or TNF-alpha-induced p38 activation, even though this drug by itself weakly activated p38. The RNA synthesis inhibitor actinomycin D, but not p38-specific inhibitor SB203580, reversed the inhibitory effect of nocodazole on TNF-alpha-induced p38 activation. Nocodazole also weakly activated JNK, but significantly activated ERK. The inhibition by nocodazole of TNF-alpha-induced p38 activation was abolished by ERK-specific inhibitor U0126. Further exploration revealed that nocodazole significantly enhanced MKP-1 expression via the ERK activity. Thus, nocodazole increases the ERK activity to enhance MKP-1 expression which inhibits p38 activation induced by TNF-alpha. PMID- 22294040 TI - Ultrafast spin-state photoswitching in a crystal and slower consecutive processes investigated by femtosecond optical spectroscopy and picosecond X-ray diffraction. AB - We report the spin state photo-switching dynamics in two polymorphs of a spin crossover molecular complex triggered by a femtosecond laser flash, as determined by combining femtosecond optical pump-probe spectroscopy and picosecond X-ray diffraction techniques. The light-driven transformations in the two polymorphs are compared. Combining both techniques and tracking how the X-ray data correlate with optical signals allow understanding of how electronic and structural degrees of freedom couple and play their role when the switchable molecules interact in the active crystalline medium. The study sheds light on crossing the border between femtochemistry at the molecular scale and femtoswitching at the material scale. PMID- 22294041 TI - Identification of genes potentially involved in bone metastasis by genome-wide gene expression profile analysis of non-small cell lung cancer in mice. AB - Lung cancer is commonly associated with multi-organ metastasis, and the bone is a frequent metastatic site for lung cancer. However, the molecular mechanism of organ-specific metastasis remains poorly understood. To elucidate this issue, we analyzed in this study genome-wide gene expression profiles of 15 metastatic lesions from three organs (bone, lung and liver) in a mouse model with multi organ metastasis properties of human non-small cell lung cancer cells (ACC LC319/bone2), using a combination of laser-microbeam microdissection and DNA microarrays. We identified 299 genes that could potentially be involved in the organ-selective nature of lung cancer metastasis. Among them, 77 were bone specifically expressed elements, including genes involved in cell adhesion, cytoskeleton/cell motility, extracellular matrix remodeling and cell-cell signaling as well as genes already known to be involved in the bone metastasis of breast cancers. Quantitative RT-PCR confirmed the specific upregulation of eight genes in bone metastasis tumors, suggesting that these genes may be involved in bone metastasis. Our findings should be helpful for a better understanding of the molecular aspects of the metastatic process in different organs, and could lead to molecular target-based anticancer drugs and prevention of metastasis, especially bone metastasis. PMID- 22294042 TI - Eccrine poromatosis associated with polychemotherapy. AB - Eccrine poroma frequently occurs as a solitary tumour, and only a few reports have described the occurrence of multiple lesions. Multiple eccrine poromas, or eccrine poromatosis, may occur in patients who have undergone radiotherapy and/or polychemotherapy. We report here four cases of multiple eccrine poromas in patients who were either undergoing, or had undergone, intensive chemotherapy (from 6 months to 16 years prior to onset). Three patients had non-Hodgkin's lymphoma and one had malignant fibrous histiocytosis. The number of lesions varied from 3 to > 20 in each patient, and all the lesions occurred on non irradiated skin. The histopathological features were consistent with those of eccrine poroma, Pinkus type. In addition to radiation therapy, intensive chemotherapy may play a role in the pathogenesis of multiple eccrine poromas even many years after treatment. PMID- 22294043 TI - Neuropathology of neurocutaneous melanosis: histological foci of melanotic neurones and glia may be undetectable on MRI. PMID- 22294044 TI - Implantation of a carotid cuff for triggering shear-stress induced atherosclerosis in mice. AB - It is widely accepted that alterations in vascular shear stress trigger the expression of inflammatory genes in endothelial cells and thereby induce atherosclerosis (reviewed in (1) and (2)). The role of shear stress has been extensively studied in vitro investigating the influence of flow dynamics on cultured endothelial cells and in vivo in larger animals and humans. However, highly reproducible small animal models allowing systematic investigation of the influence of shear stress on plaque development are rare. Recently, Nam et al. introduced a mouse model in which the ligation of branches of the carotid artery creates a region of low and oscillatory flow. Although this model causes endothelial dysfunction and rapid formation of atherosclerotic lesions in hyperlipidemic mice, it cannot be excluded that the observed inflammatory response is, at least in part, a consequence of endothelial and/or vessel damage due to ligation. In order to avoid such limitations, a shear stress modifying cuff has been developed based upon calculated fluid dynamics, whose cone shaped inner lumen was selected to create defined regions of low, high and oscillatory shear stress within the common carotid artery. By applying this model in Apolipoprotein E (ApoE) knockout mice fed a high cholesterol western type diet, vascular lesions develop upstream and downstream from the cuff. Their phenotype is correlated with the regional flow dynamics as confirmed by in vivo Magnetic Resonance Imaging (MRI): Low and laminar shear stress upstream of the cuff causes the formation of extensive plaques of a more vulnerable phenotype, whereas oscillatory shear stress downstream of the cuff induces stable atherosclerotic lesions. In those regions of high shear stress and high laminar flow within the cuff, typically no atherosclerotic plaques are observed. In conclusion, the shear stress-modifying cuff procedure is a reliable surgical approach to produce phenotypically different atherosclerotic lesions in ApoE-deficient mice. PMID- 22294045 TI - A vertically aligned carbon nanotube-based impedance sensing biosensor for rapid and high sensitive detection of cancer cells. AB - A novel vertically aligned carbon nanotube based electrical cell impedance sensing biosensor (CNT-ECIS) was demonstrated for the first time as a more rapid, sensitive and specific device for the detection of cancer cells. This biosensor is based on the fast entrapment of cancer cells on vertically aligned carbon nanotube arrays and leads to mechanical and electrical interactions between CNT tips and entrapped cell membranes, changing the impedance of the biosensor. CNT ECIS was fabricated through a photolithography process on Ni/SiO(2)/Si layers. Carbon nanotube arrays have been grown on 9 nm thick patterned Ni microelectrodes by DC-PECVD. SW48 colon cancer cells were passed over the surface of CNT covered electrodes to be specifically entrapped on elastic nanotube beams. CNT arrays act as both adhesive and conductive agents and impedance changes occurred as fast as 30 s (for whole entrapment and signaling processes). CNT-ECIS detected the cancer cells with the concentration as low as 4000 cells cm(-2) on its surface and a sensitivity of 1.7 * 10(-3)Omega cm(2). Time and cell efficiency factor (TEF and CEF) parameters were defined which describe the sensor's rapidness and resolution, respectively. TEF and CEF of CNT-ECIS were much higher than other cell based electrical biosensors which are compared in this paper. PMID- 22294046 TI - Rapidly-Exploring Roadmaps: Weighing Exploration vs. Refinement in Optimal Motion Planning. AB - Computing globally optimal motion plans requires exploring the configuration space to identify reachable free space regions as well as refining understanding of already explored regions to find better paths. We present the rapidly exploring roadmap (RRM), a new method for single-query optimal motion planning that allows the user to explicitly consider the trade-off between exploration and refinement. RRM initially explores the configuration space like a rapidly exploring random tree (RRT). Once a path is found, RRM uses a user-specified parameter to weigh whether to explore further or to refine the explored space by adding edges to the current roadmap to find higher quality paths in the explored space. Unlike prior methods, RRM does not focus solely on exploration or refine prematurely. We demonstrate the performance of RRM and the trade-off between exploration and refinement using two examples, a point robot moving in a plane and a concentric tube robot capable of following curved trajectories inside patient anatomy for minimally invasive medical procedures. PMID- 22294047 TI - Essential role of IL-6 in protection against H1N1 influenza virus by promoting neutrophil survival in the lung. AB - Influenza virus infection is considered a major worldwide public health problem. Seasonal infections with the most common influenza virus strains (e.g., H1N1) can usually be resolved, but they still cause a high rate of mortality. The factors that influence the outcome of the infection remain unclear. Here, we show that deficiency of interleukin (IL)-6 or IL-6 receptor is sufficient for normally sublethal doses of H1N1 influenza A virus to cause death in mice. IL-6 is necessary for resolution of influenza infection by protecting neutrophils from virus-induced death in the lung and by promoting neutrophil-mediated viral clearance. Loss of IL-6 results in persistence of the influenza virus in the lung leading to pronounced lung damage and, ultimately, death. Thus, we demonstrate that IL-6 is a vital innate immune cytokine in providing protection against influenza A infection. Genetic or environmental factors that impair IL-6 production or signaling could increase mortality to influenza virus infection. PMID- 22294048 TI - M cell-depletion blocks oral prion disease pathogenesis. AB - Many prion diseases are orally acquired. Our data show that after oral exposure, early prion replication upon follicular dendritic cells (FDC) in Peyer's patches is obligatory for the efficient spread of disease to the brain (termed neuroinvasion). For prions to replicate on FDC within Peyer's patches after ingestion of a contaminated meal, they must first cross the gut epithelium. However, the mechanism through which prions are conveyed into Peyer's patches is uncertain. Within the follicle-associated epithelium overlying Peyer's patches are microfold cells (M cells), unique epithelial cells specialized for the transcytosis of particles. We show that following M cell-depletion, early prion accumulation upon FDC in Peyer's patches is blocked. Furthermore, in the absence of M cells at the time of oral exposure, neuroinvasion and disease development are likewise blocked. These data suggest M cells are important sites of prion uptake from the gut lumen into Peyer's patches. PMID- 22294049 TI - c-Ets1 inhibits the interaction of NF-kappaB and CREB, and downregulates IL-1beta induced MUC5AC overproduction during airway inflammation. AB - Mucin hypersecretion is frequently observed in many inflammatory diseases of the human respiratory tract. As mucin hypersecretion refers to uncontrolled mucin expression and secretion during inflammation, studies examining the negative control mechanisms of mucin hypersecretion are vital in developing novel therapeutic medications. We hypothesized that the c-Ets1 induced by interleukin (IL)-1beta would decrease MUC5AC overproduction by inhibiting the interaction of NF-kappaB with cAMP response element-binding protein (CREB) in vivo. Stimulation with IL-1beta caused the direct binding of NF-kappaB and CREB to the MUC5AC promoter, thus increasing MUC5AC gene expression. However, IL-1beta-induced MUC5AC messenger RNA levels were surprizingly downregulated by c-Ets1 (located 938 to -930). Interestingly, c-Ets1 also suppressed IL-1beta-induced MUC5AC gene expression in vitro and in vivo by disrupting the interaction of NF-kappaB with CREB on the MUC5AC promoter. In addition, c-Ets1 also inhibited significant morphologic changes and inflammatory cell infiltration after IL-1beta exposure in mouse lungs infected with either wild-type or shRNA-c-Ets1. Moreover, reactive oxygen species produced by NOX4 increased c-Ets1 gene expression and MUC5AC gene expression in alveolar macrophages from bronchoalveolar lavage fluid. These results suggest a molecular paradigm for the establishment of a novel mechanism underlying the negative regulation of mucin overproduction, thus enhancing our understanding of airway inflammation. PMID- 22294050 TI - Everolimus exhibits efficacy as a radiosensitizer in a model of non-small cell lung cancer. AB - Signaling pathways that activate mTOR (mammalian target of rapamycin) are altered in many human cancers and these alterations are associated with prognosis and treatment response. mTOR inhibition can restore sensitivity to DNA damaging agents such as cisplatin. The rapamycin derivative everolimus exhibits antitumor activity and is approved for patients with renal cell cancer. Clinically, everolimus has also been evaluated in patients with advanced non-small cell lung cancer (NSCLC) that were refractory to chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitors. We tested the effects of combined treatment with everolimus (RAD001) and fractionated radiation using a xenograft model of human NSCLC (A549 cells). In growth studies, mean tumor volume was reduced in the everolimus plus 30 Gy cohort with significant tumor growth suppression compared to 30 Gy alone (p=0015), or everolimus alone (p<0.001, ANOVA). everolimus (20 nM) significantly reduced protein levels of the mTOR downstream effector p70-S6K compared with radiation and vehicle (p=0.05, ANOVA) and significantly suppressed phospho-p70-S6K levels compared with all other treatments (p<0.001, ANOVA). We also evaluated everolimus and radiation effects on gene expression in A549 cells. Everolimus +/- 5 Gy suppressed endothelin 1 and lactate dehydrogenase expression and increased VEGFA, p21, hypoxia-inducible factor-1alpha and SLC2A1 (facilitated glucose transporter 1). mTOR mRNA levels were unaffected while TNF-alpha levels were increased with everolimus + 5 Gy compared to either treatment alone. These findings suggest that everolimus increases the antitumor activity of radiation. Clinical trials combining everolimus with fractionated radiation in patients with NSCLC are warranted. PMID- 22294051 TI - miR-221/222 is the regulator of Cx43 expression in human glioblastoma cells. AB - The miR-221/222 cluster is significantly upregulated in malignant glioma cells and regulates the expression of multiple genes associated with glioma cell proliferation, invasion and apoptosis, which was shown in our previous studies. Cx43 has been identified as a tumor suppressor and major component for the establishment of gap junction intercellular communication (GJIC) in glial cells, which is frequently reduced or deleted in high-grade gliomas. According to bioinformatic analysis, connexin 43 (Cx43) may be one of the target genes of miR 221/222. The aim of the present study was to validate Cx43 as a target gene of miR-221/222 and to determine whether overexpression of miR-221/222 is one of the molecular mechanisms for the reduced expression of Cx43 in malignant gliomas. We transfected miR-221/222 antisense oligonucleotides (AS-miR-221/222) into U251 human glioblastoma cells using a lipofectamine method. Northern blot analysis was conducted to detect the expression of the miR-221/222 cluster. Luciferase reporter assays were exploited to confirm Cx43 as a target gene of miR-221/222. Cx43 expression was assessed by western blotting and immunofluorescence staining. Scrape loading and dye transfer (SLDT) assays were used for examination of GJIC. Proliferation and invasion of U251 cells were evaluated by MTT and transwell assays, respectively. Cell cycle kinetics and apoptosis were determined with flow cytometry. We found that expression of the miR-221/222 cluster was significantly reduced while Cx43 expression was upregulated in U251 cells transfected with AS miR-221/222, and the GJIC deficiency in parental U251 cells was re-established. Moreover, the luciferase activity determined by the luciferase reporter assay was enhanced in AS-miR-221/222-treated cells, and cell proliferation and invasion were suppressed while apoptosis was induced. We conclude that miR-221/222 function as oncogenic microRNAs in human gliomas, at least in part, by targeting Cx43. PMID- 22294052 TI - Central nervous system lymphoma occurring in a patient with neurofibromatosis type 1 (von Recklinghausen disease). AB - Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder, which confers an increased risk of a wide range of cancers, and malignant tumors are the most common cause of death in individuals with NF1. Although in children with NF1, the most common neoplasms are optic nerve gliomas and brain tumors, an elevated risk of myeloid leukemia and an increased relative risk of acute lymphoblastic leukemia and non-Hodgkin lymphoma were reported. In adults with NF1, the relative risk of brain tumor is 100 times higher than in the general population. Cases of malignant lymphoma occurring in NF1 adult patients have been reported. However, the association between NF1 and lymphoproliferative diseases is still debated. We report a case of CNS primitive lymphoma in an adult patient who resulted positive for NF1 at genetic testing. At present, only one case of CNS lymphoma in an adult patient displaying clinical criteria for NF1 diagnosis has been reported. PMID- 22294053 TI - Serum carnitine levels and levocarnitine supplementation in institutionalized Huntington's disease patients. AB - Along with antioxidant properties, carnitine is an important regulator of lipid metabolism in humans. While beneficial effects of carnitine have been demonstrated in animal models of Huntington's disease (HD), metabolism of carnitine has not been studied in humans with this illness. In this retrospective database review from 23 patients admitted to a HD-specialized nursing home unit, we found a relatively high prevalence of hypocarnitinemia (6 cases, 26%). Our review suggests that catabolism and chronic valproate use predisposed our patients to develop hypocarnitinemia. The patients with low serum carnitine levels who received levocarnitine supplementation, during a mean period of 7.3 months, showed improvement in motor, cognitive and behavioral measures. We hypothesize that observed improvement related to the resolution of reversible metabolic encephalopathy and myopathy associated with secondary carnitine deficiency. In conclusion, notwithstanding its limitations, this is the first study to report measurements of carnitine levels in HD patients, revealing relatively high prevalence of hypocarnitinemia in our population. Our findings suggest that HD patients with hypocarnitinemia may benefit from low-dose levocarnitine supplementation. Further studies of carnitine metabolism and supplementation in HD patients are warranted. PMID- 22294054 TI - Erythropoietin attenuates 6-hydroxydopamine-induced apoptosis via glycogen synthase kinase 3beta-mediated mitochondrial translocation of Bax in PC12 cells. AB - The aim of this study was to determine the mechanism by which erythropoietin (EPO) suppressed 6-hydroxydopamine (6-OHDA)-induced apoptosis. Our results showed that 6-OHDA remarkably decreased phosphorylation of glycogen synthase kinase 3beta (GSK3beta) as well as enhanced the level of Bax in the mitochondria. Besides, 6-OHDA decreased the mitochondrial expression of Bcl-2 without altering the cytoplasmic expression of Bcl-2. In line with these results, 6-OHDA treatment enhanced the apoptosis and caspase 3 activity in PC12 cells. These findings indicated that mitochondrial dysfunction was involved in the neurotoxicity of 6 OHDA and GSK3beta might act upstream of Bax/Bcl-2 and the caspase 3 pathways in 6 OHDA-treated PC12 cells. Furthermore, EPO reduced 6-OHDA-induced growth inhibition. Western blot exhibited that GSK3beta inhibitor 4-benzyl-2-methyl-1, 2,4-thiadiazolidine-3, 5-dione (TDZD8) and EPO not only increased the phosphorylation of GSK3beta but also inhibited the mitochondrial translocation of Bax. In agreement with these results, EPO and TDZD8 obviously increased the mitochondrial expression of Bcl-2. Finally, TDZD-8 and EPO significantly suppressed the enhanced apoptosis and activity of caspase 3 induced by 6-OHDA. Taken together, GSK3beta-mediated mitochondrial cell death pathway is involved in the neuroprotective effect of EPO against 6-OHDA-induced apoptosis. PMID- 22294056 TI - Dense and vertically-aligned centimetre-long ZnS nanowire arrays: ionic liquid assisted synthesis and their field emission properties. AB - Based on the self-ordering behavior of ionic liquids on solid surface, a gold ion containing ionic liquid was employed to obtain a uniform pattern of gold nanoparticles on Si substrate. Using this catalytic pattern, super-dense, centimetre long, well-crystallized and vertically-aligned ZnS nanowire arrays were then generated. It was found that the densely-packed gold nanoparticles played a key role in the nanowire alignment. Furthermore, the field-emission measurements show that the present ultralong ZnS nanowires arrays possess a low turn-on field of 3.69 V MUm(-1) and a high field-enhancement factor of 1215.4, indicating they are valuable field emitters. PMID- 22294055 TI - Involvement of AMP-activated protein kinase in TGF-beta-stimulated VEGF synthesis in osteoblasts. AB - It is generally recognized that AMP-activated protein kinase (AMPK) acts as a key regulator of energy homeostasis. We have previously shown that transforming growth factor-beta (TGF-beta) stimulates synthesis of vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase, stress activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether AMPK is involved in the TGF-beta-stimulated VEGF synthesis in osteoblast-like MC3T3-E1 cells. TGF-beta time-dependently induced the phosphorylation of the AMPK alpha-subunit (Thr172) and the AMPK beta-subunit (Ser108). Compound C, an AMPK inhibitor, significantly reduced the TGF-beta-stimulated VEGF release. The inhibitory effect of compound C was also observed in normal human osteoblasts (NHOst). Although compound C failed to affect the TGF-beta-induced phosphorylation of SAPK/JNK, p38 MAP kinase or Smad2, it markedly suppressed the TGF-beta-induced phosphorylation of both MEK1/2 and p44/p42 MAP kinase. In addition, compound C significantly suppressed the VEGF mRNA expression induced by TGF-beta. Taken together, our results strongly suggest that AMPK is involved in TGF-beta-stimulated VEGF synthesis, and that it functions at a point upstream of MEK1/2. PMID- 22294057 TI - Minimally invasive intrathoracic anastomosis after Ivor Lewis esophagectomy for cancer: a review of transoral or transthoracic use of staplers. AB - BACKGROUND: Minimally invasive Ivor Lewis esophagectomy is one of the approaches used worldwide for treating esophageal cancer. Optimization of this approach and especially identifying the ideal intrathoracic anastomosis technique is needed. To date, different types of anastomosis have been described. A literature search on the current techniques and approaches for intrathoracic anastomosis was held. The studies were evaluated on leakage and stenosis rate of the anastomosis. METHODS: The PubMed electronic database was used for comprehensive literature search by two independent reviewers. RESULTS: Twelve studies were included in this review. The most frequent applied technique was the stapled anastomosis. Stapled anastomoses can be divided into a transthoracic or a transoral introduction. This stapled approach can be performed with a circular or linear stapler. The reported anastomotic leakage rate ranges from 0 to 10%. The reported anastomotic stenosis rate ranges from 0 to 27.5%. CONCLUSIONS: This review has found no important differences between the two most frequently used stapled anastomoses: the transoral introduction of the anvil and the transthoracic. Clinical trials are needed to compare different methods to improve the quality of the intrathoracic anastomosis after esophagectomy. PMID- 22294058 TI - Search for the molecular basis of ultra-rapid CYP2C9-catalysed metabolism: relationship between SNP IVS8-109A>T and the losartan metabolism phenotype in Swedes. AB - AIM: To search for a relationship between ultra-rapid metabolism catalysed by cytochrome P450 2C9 (CYP2C9) and its genotypes. METHODS: DNA from a Swedish ultra rapid metaboliser patient [losartan metabolic ratio (MR) <0.13] and three healthy Swedes with normal CYP2C9 activity and a MR of about 1 were assessed for variation in the CYP2C9 gene. Direct DNA sequencing was performed for all exons and exon-intron junctions and also for -2100 bp of the 5'-flanking regions of the CYP2C9 gene. This analysis revealed four intronic mutations [single nucleotide polymorphisms (SNPs) 1-4] in the three samples with normal MR while no variation was observed in the ultra-rapid metaboliser. PCR/restriction fragment length polymorphism and allele-specific PCR methods were subsequently developed to screen 85 Swedes and 128 Koreans without CYP2C9*2 or *3. RESULTS: We found a significant relationship between SNP 4 (IVS8-109A>T) and CYP2C9 activity (chi2 test, p=0.011) in the Swedes. Twenty Swedes with the lowest MR were compared with 20 Swedes with the highest MR, revealing a strong association (p00.001) between SNP4 and higher MR. For homozygous SNP 1 (IVS1+83T>C), SNP 2 (IVS2+73T>C), and SNP 3 (IVS6+95A>G), no phenotype and genotype relationships were found, but theMRwas generally higher among the Swedes compared to the Koreans (Mann-Whitney test, p<0.05). CONCLUSIONS: We found that the SNP 4 IVS8-109T allele is associated with a higher CYP2C9 MR in healthy Swedish subjects, but further investigations need to be carried out to establish a molecular explanation for ultra-rapid CYP2C9- catalysed metabolism. Haplotype based on SNPs 1-4 did not seem to contribute to variation in the MR of the Korean subjects nor play a role in determining the MR of the Swedish ones. PMID- 22294059 TI - Differences in lercanidipine systemic exposure when administered according to labelling: in fasting state and 15 minutes before food intake. AB - PURPOSE: The aim of this study was to compare the systemic exposure of lercanidipine (Zanidip) after oral administration in the fasted state and 15 min before food intake (meals) to investigate if the recommendations in the Summary of Product Characteristics (SPC) with respect to the intake of meals are adequate. METHODS: The results of three pilot bioequivalence studies performed to develop a lercanidipine generic product, where Zanidip was administered consistently as reference product in the fasted state or 15 min before a standard breakfast, were compared to estimate the drug-food interaction and the similarity of the methods of administration defined in the SPC. RESULTS: The ingestion of a standard (non-high-fat, non-high-calorie) meal 15 min after drug intake increased the area under the concentration-time curve (AUC(0-t)) of S-lercanidipine by 1.78 fold [90% confidence interval (CI) 1.48-2.15, P<0.0001] and the maximum concentration (Cmax) of Slercanidipine by 1.82-fold (90% CI 1.46-2.28, P<0.0001). These values are close to the twofold increase that has been described when Zanidip was taken immediately after a carbohydrate-rich meal. Higher levels would be expected with a high-fat, high-calorie meal. CONCLUSIONS: As intake with a carbohydrate-rich meal is not recommended in the SPC of Zanidip because a twofold difference was considered to be clinically relevant, the intake of lercanidipine only 15 min before food intake does not seem to be consistent with this recommendation. The Marketing Authorisation Holder should clarify the dosing instructions in relation to meals and identify a sufficient time-lapse to ensure an exposure similar to that obtained in phase III clinical efficacy studies. PMID- 22294060 TI - Adverse drug reactions: analysis of spontaneous reporting system in Europe in 2007-2009. AB - PURPOSE: Spontaneous reporting systems in European countries are crucial for collecting adverse drug reaction (ADR) reports. The aim of this study was to evaluate reporting activity among countries and their strategy to increase the number of reports. We also established the best measure for assessment quantity of reports. METHODS: This was a retrospective observational study based on questionnaires and annual reports. The most reliable measure of reporting was determined by Spearman correlation coefficients. RESULTS: Data collected in spontaneous reporting systems in 26 European countries were analysed. In 2007, 2008 and 2009, the average value of reports per year per million inhabitants based on the safety databases of countries was 208, 236, 286, respectively; in comparison, that of Eudra- Vigilance was 311, 453 and 435, respectively. Twelve countries reached a significant level for signal detection of ADRs in 2009. The population-based reporting ratio (PBRR) was correlated to the total expenditure on health (rho=0.499, p=0.023, n=21), public expenditure on health (rho=0.477, p=0.035, n=20), density of physicians (rho=0.336, p=0.136, n=21) and expenditure on pharmaceuticals (rho=0.365, p=0.114, n=20). Strategies of regulatory authorities to increase reporting were determined. CONCLUSIONS: The results of this study make several noteworthy contributions regarding national spontaneous reporting systems. The relevance of the PBRR for the measurement reporting activity is clearly supported by the current findings. This study also shows that there is a general trend towards increased reporting activity. This is maintained by regional centres and encouragement of reporting. A further study would be helpful to assess the effectiveness of reporting systems at both the national and European level. PMID- 22294062 TI - Dengue research in Singapore marking the inaugural ASEAN Dengue Day. PMID- 22294063 TI - Subcutaneous infection with non-mouse adapted Dengue virus D2Y98P strain induces systemic vascular leakage in AG129 mice. AB - INTRODUCTION: Dengue (DEN) is a mosquito-borne viral disease which has become an increasing economic and health burden for the tropical and subtropical world. Plasma leakage is the most life threatening condition of DEN and may lead to hypovolaemic shock if not properly managed. MATERIALS AND METHODS: We recently reported a unique dengue virus strain (D2Y98P) which upon intraperitoneal (IP) administration to immunocompromised mice led to systemic viral dissemination, intestine damage, liver dysfunction, and increased vascular permeability, hallmarks of severe DEN in patients (Tan et al, PLoS Negl Trop Dis 2010;4:e672). RESULTS: Here we report the clinical manifestations and features observed in mice subcutaneously (SC) infected with D2Y98P, which is a route of administration closer to natural infection. Similar to the IP route, increased vascular permeability, intestine damage, liver dysfunction, transient lymphopenia (but no thrombocytopenia) were observed in the SC infected mice. Furthermore, the SC route of infection was found more potent than the IP route whereby higher viral titers and earlier time-of-death rates were measured. In addition, various staining approaches revealed structurally intact blood vessels in the moribund animals despite pronounced systemic vascular leakage, as reported in dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) patients. Interestingly, measurement of soluble mediators involved in vascular permeability indicated that vascular leakage may occur at an early stage of the disease, as proposed in DEN patients. CONCLUSION: We believe that this novel mouse model of DEN-associated vascular leakage will contribute to a better understanding of DEN pathogenesis and represents a relevant platform for testing novel therapeutic treatments and interventions. PMID- 22294064 TI - Dengue knowledge, attitudes, and practices among primary care physicians in Singapore. AB - INTRODUCTION: Dengue fever remains a significant public health concern in Singapore. Appropriate, timely diagnosis and risk stratification for severe disease are crucial in the optimal management of this illness. In the outpatient setting, the primary care physician plays a key role in dengue diagnosis, management, and triage. We present a descriptive analysis of the variations in dengue knowledge, attitudes, and practices among primary care physicians (PCPs) in Singapore. MATERIALS AND METHODS: A survey of 25 multiple-choice questions was mailed to 2000 PCPs in Singapore. Responses were analysed by physician age group (21-40, 41-60, and >61) and practice setting (government subsidised polyclinic or private practice). RESULTS: Of the 3 questions assessing dengue knowledge, 89.9% chose 2 or 3 of the preferred responses. Half of the respondents utilised dengue diagnostic tests at least 50% of the time, and 75% used serology when doing so. Older respondents and those from private practices used diagnostic tests more often than their counterparts, and both groups favoured non-serology tests. About 85% of surveyed PCPs monitored confirmed or suspected cases daily, and one-third referred patients to a hospital always or often. CONCLUSIONS: While no major gaps in knowledge about dengue were identified in PCPs in Singapore, there were significant variations in clinical practice by physician age group and practice setting. The results of this survey provide a useful opportunity to identify strengths and areas in need of improved awareness in primary care management of dengue. PMID- 22294065 TI - When less is more: can we abandon prophylactic platelet transfusion in Dengue fever? AB - Dengue fever (DF) has several hematological manifestations including thrombocytopenia and increased bleeding risk. Prophylactic platelet transfusion in the absence of major bleeding-is utilized in DF with thrombocytopenia with the intention of preventing hemorrhagic complications. However, prophylactic platelet transfusion in DF is neither standardized nor supported by clinical evidence. We conclude that risks, costs and poor resource utilization associated with prophylactic platelet transfusion in DF far outweigh any potential hematological benefit, and as such, should not constitute routine clinical practice. PMID- 22294066 TI - A calcified tumour in the pelvis. PMID- 22294067 TI - Coexisting metastatic choriocarcinoma and bladder adenocarcinoma of common germ cell origin. PMID- 22294068 TI - Peripheral ulcerative keratitis associated with multiple myeloma. PMID- 22294069 TI - A case of hemoglobin SE presenting with sickle cell crisis: case report and histological correlation. PMID- 22294070 TI - A patient with abdominal compartment syndrome and perforated transverse colon successfully managed with ECMO. PMID- 22294071 TI - Renal Sympathetic Denervation for Treatment of Hypertension. AB - OPINION STATEMENT: Sympathetic nervous system activation of the heart, kidney and peripheral vasculature increases cardiac output, fluid retention and vascular resistance and plays an important role in acute and chronic BP elevation. Renal sympathetic denervation via a percutaneous radiofrequency catheter based approach is a safe and effective procedure that lowers BP in patients with resistant hypertension. Exploratory studies in patients with resistant hypertension and a variety of comorbidities, including insulin resistance/metabolic syndrome, obstructive sleep apnea and the polycystic ovary syndrome, have shown benefit of renal denervation in attenuating the severity of the comorbid conditions, as well as reducing BP. However, more studies are needed to further address the long term effects of renal denervation and its safety and effectiveness in other disease states such as congestive heart failure. PMID- 22294072 TI - Disseminated cutaneous glomangiomas in an adolescent boy. PMID- 22294073 TI - Characterization of cannabinoid receptors. AB - This unit describes the use of cannabinoid radioligands in competitive binding assays for determining affinity parameters (IC(50), K(i)) of unlabeled compounds at cloned CB1 and CB2 receptors expressed in cells. PMID- 22294074 TI - Radioligand binding assays for the glycine site on N-methyl-D-aspartate receptors. AB - This unit describes a competitive binding assay for the glycine binding site on the NMDA subtype of glutamate receptors in rat brain homogenates. Agonists of the NMDA receptor associated glycine binding site have been proposed as potential therapeutics in cognitive disorders. Conversely, antagonists may be useful in a variety of disorders associated with excessive activation of EAA receptors, including Parkinson, Huntington and Alzheimer Diseases, and neuropathic pain, among others. This unit describes a competitive binding assay for the glycine binding site on the NMDA subtype of glutamate receptors in rat. PMID- 22294075 TI - Use of electrophysiological methods in the study of recombinant and native neuronal ligand-gated ion channels. AB - This unit is geared towards investigators wishing to study the effects of externally and internally applied agents on the behavior of ligand-gated ion channels (LGICs, specifically the GABAA receptor). The reader is taken through a number of electrophysiological techniques applied to whole cell and excised patch recordings of recombinant and native GABAA receptor subtypes used in the generation and analysis of a variety of pharmacological parameters. These data interpretations form the basis for the analysis of potentially novel pharmacological agents active at the GABAA receptor target, but could equally be applied to other LGICs. The analysis is extended to incorporate post-synaptic inhibitory events in hippocampal neurons. Complementary descriptions of how tissues for such studies are prepared from recombinant and native receptor preparations are included. Attention is given to the physiological phenomena most relevant to everyday scientific literature. PMID- 22294076 TI - Overview of animal models of asthma. AB - Asthma is an inflammatory disease characterized by airways obstruction, airways hyperresponsiveness, excessive mucous secretion and cough. Guinea pig airways display many anatomical, physiological and pharmacological attributes of human airways, making this species ideal for modeling the asthmatic condition. This unit provides an overview of animal models of asthma, including definitions, descriptions of available animal models, and discussion of numerous critical issues to consider before designing a model to study this complex disease. PMID- 22294077 TI - Guinea pig models of asthma. AB - This unit describes methods for establishing guinea pig models of asthma. Detailed descriptions are provided so that investigators can establish preparations in which bronchoconstriction, airways hyperresponsiveness, cough and airways inflammation can be studied. PMID- 22294078 TI - Models of cardiac ischemia-reperfusion injury in dogs and rats. AB - A marked reduction in coronary blood flow produces a reduction in myocardial function, electrocardiographic abnormalities and eventually a myocardial infarction if the ischemic episode were to persist for more than 20 to 30 min. There have been numerous studies in animal models in search of a magic bullet or drug that can ameliorate these symptoms and result in a reduction in infarct size, improvement in the recovery of contractile function, and abrogation of malignant ventricular arrhythmias in humans. This unit describes two animal models of myocardial ischemia/reperfusion injury which are used to evaluate pharmacological agents that may eventually demonstrate cardioprotective activity in a clinical setting. PMID- 22294079 TI - Intraperitoneal and subcutaneous tumor models for assessing anti-neoplastic agents in rodents. AB - Evaluation of compounds for in vivo antineoplastic activity can be achieved in a variety of animal models. Two models commonly employed for these studies are the intraperitoneal challenge survival model and the subcutaneous tumor implant model. The challenge survival model involves intraperitoneal tumor inoculation, test compound treatment and monitoring for survival. This assay can be modulated for stringency by altering the treatment dose, route and schedule. The second model, subcutaneous tumor implants, is more strenuous as the test compound must cross physiologic barriers to reach the target tumor. Additionally, the subcutaneous model is more labor intensive to setup, monitor and evaluate. PMID- 22294080 TI - Electrocardiographic toxicity in the guinea pig. AB - Abnormalities of cardiac rhythm are one of the most common clinical problems in cardiology and arise as the result of either disorders of cardiac impulse formation or conduction, or a combination of both. It has been established that some classes of drugs, such as tricyclic antidepressants (e.g., imipramine), cardiac glycosides (e.g., digoxin), and Class I or Class III antiarrhythmic drugs (e.g., quinidine or amiodarone) can produce electrocardiographic toxicity in humans. It is therefore highly advisable to assess the effect of any new compound in this respect, during the early phases of drug development. This unit presents a protocol to detect the electrocardiographic toxicity of compounds in the anesthetized guinea pig. PMID- 22294081 TI - Tissue expression profiling using real-time PCR. AB - The recent development of real-time PCR allows for the rapid and accurate quantitation of gene expression in cells and tissues. Real-time PCR instrumentation is designed for the simultaneous quantitation of gene expression from a few samples up to 384 samples. The normal tissue expression profile of a gene can provide useful insights into its potential role in normal physiological processes. When combined with the tissue expression profile of the gene in diseased tissues, information concerning the potential role in pathological processes can be determined. This unit describes a protocol to determine the relative abundance of mRNA in a panel of human tissues using real-time PCR. PMID- 22294082 TI - In vivo measurement of blood-brain barrier permeability. AB - This unit describes various protocols for the in vivo quantitation of drug permeability across the rodent blood-brain barrier. Methods for the measurement of drug influx and efflux are described, and support protocols are provided for determining intravascular capillary volume and cerebral perfusion flow. An in situ perfusion technique is also provided for assessing whether transport of a test compound occurs by carrier-mediated or saturable transport. PMID- 22294083 TI - Place preference test in rodents. AB - Conditioned place preference is a behavioral model currently used to measure the rewarding properties induced by the administration of a drug. In this paradigm, the rewarding properties of a compound are associated with the particular characteristics of a given environment. Advantages of this test are the absence of any instrumental learning and the possibility of evaluating reinforcing effects in the absence of the test substance. Due to the recent availability of multiple lines of genetically modified mice, this unit has been updated to include procedures for testing place preference in both rats and mice. Details are also provided for evaluating drug effects using this procedure. PMID- 22294084 TI - In vitro enzymatic assays for Ser/Thr-selective protein kinases. AB - Medium and high throughput methods for measuring the activities of Ser/Thr selective protein kinases are described. These methods utilize radiochemical detection, fluorescence polarization, and ultraviolet spectroscopy to monitor transfer of the gamma-phosphoryl group of ATP to protein or peptide substrates. These assays have utility in characterizing protein kinase inhibitors and in mechanistic studies. PMID- 22294085 TI - Determination of the stability of drugs in plasma. AB - In order for a drug to be effective, enough of the active form must reach the target to elicit the desired effect. The first-pass effect for drugs taken orally is well known but the metabolism of drugs in plasma must also be considered during the drug discovery and development process. For instance, hydrolysis of a compound by plasma enzymes can significantly alter the bioavailability of the active compound. This unit describes methods for the determination of the stability of compounds in plasma. PMID- 22294086 TI - Monitoring cleaved caspase-3 activity and apoptosis of immortalized oligodendroglial cells using live-cell imaging and cleaveable fluorogenic-dye substrates following potassium-induced membrane depolarization. AB - The central nervous system can experience a number of stresses and neurological insults, which can have numerous adverse effects that ultimately lead to a reduction in neuronal population and function. Damaged axons can release excitatory molecules including potassium or glutamate into the extracellular matrix, which in turn, can produce further insult and injury to the supporting glial cells including astrocytes and oligodendrocytes. If the insult persists, cells will undergo programmed cell death (apoptosis), which is regulated and activated by a number of well-established signal transduction cascades. Apoptosis and tissue necrosis can occur after traumatic brain injury, cerebral ischemia, and seizures. A classical example of apoptotic regulation is the family of cysteine-dependent aspartate-directed proteases, or caspases. Activated proteases including caspases have also been implicated in cell death in response to chronic neurodegenerative diseases including Alzheimer's, Huntington's, and Multiple Sclerosis. In this protocol we describe the use of the NucView 488 caspase-3 substrate to measure the rate of caspase-3 mediated apoptosis in immortalized N19 oligodendrocyte (OLG) cell cultures, following exposure to different extracellular stresses such as high concentrations of potassium or glutamate. The conditionally-immortalized N19-OLG cell line (representing the O2A progenitor) was obtained from Dr. Anthony Campagnoni (UCLA Semel Institute for Neuroscience), and has been previously used to study molecular mechanisms of myelin gene expression and signal transduction leading to OLG differentiation. We have found this cell line to be robust with respect to transfection with exogenous myelin basic protein (MBP) constructs fused to either RFP or GFP (red or green fluorescent protein). Here, the N19-OLG cell cultures were treated with either 80 mM potassium chloride or 100 mM sodium glutamate to mimic axonal leakage into the extracellular matrix to induce apoptosis. We used a bi-functional caspase-3 substrate containing a DEVD (Asp-Glu-Val-Asp) caspase-3 recognition subunit and a DNA-binding dye. The substrate quickly enters the cytoplasm where it is cleaved by intracellular caspase-3. The dye, NucView 488 is released and enters the cell nucleus where it binds DNA and fluoresces green at 488 nm, signaling apoptosis. Use of the NucView 488 caspase-3 substrate allows for live-cell imaging in real time. In this video, we also describe the culturing and transfection of immortalized N19-OLG cells, as well as live-cell imaging techniques. PMID- 22294087 TI - Crucial cross-talk of interleukin-1beta and progesterone in human choriocarcinoma. AB - Choriocarcinoma is a highly malignant epithelial tumour that is most often associated with hydatidiform mole and presents the most common emergency medical problem in the management of trophoblast disease. We hypothesise that the hormones/cytokines present within the tumour microenvironment play key roles in the development of choriocarcinoma. In this study we assessed the effects of interleukin-1beta (IL-1beta) on cell death in the presence or absence of the sex hormone progesterone using two choriocarcinoma cell lines (BeWo and JEG-3) as in vitro experimental models. Although IL-1beta induced cell death in both cell lines, the effect was more pronounced in JEG-3 cells, where cell death reached 40% compared to 15% in BeWo cells. Cell death of JEG-3 cells in response to IL 1beta was significantly decreased by co-treatment with 100 nM and 1000 nM progesterone and completely abolished at a progesterone concentration of 1000 nM. Progesterone was also able to induce phosphorylation of ERK1/2 in these cells. Pretreatment of JEG-3 cells with a specific MAPK inhibitor (UO126) inhibited progesterone's inhibitory effect on cell death. Collectively, these data provide evidence of cross-talk between progesterone and IL-1beta in this aggressive and poorly understood tumour that involves activation of a MAPK pathway and involvement of numerous progesterone receptors. PMID- 22294088 TI - MR spectroscopic studies of the brain in psychiatric disorders. AB - The measurement of brain metabolites with magnetic resonance spectroscopy (MRS) provides a unique perspective on the brain bases of neuropsychiatric disorders. As a context for interpreting MRS studies of neuropsychiatric disorders, we review the characteristic MRS signals, the metabolic dynamics,and the neurobiological significance of the major brain metabolites that can be measured using clinical MRS systems. These metabolites include N-acetylaspartate(NAA), creatine, choline-containing compounds, myo-inositol, glutamate and glutamine, lactate, and gamma-amino butyric acid (GABA). For the major adult neuropsychiatric disorders (schizophrenia, bipolar disorder, major depression, and the anxiety disorders), we highlight the most consistent MRS findings, with an emphasis on those with potential clinical or translational significance. Reduced NAA in specific brain regions in schizophrenia, bipolar disorder, post traumatic stress disorder, and obsessive-compulsive disorder corroborate findings of reduced brain volumes in the same regions. Future MRS studies may help determine the extent to which the neuronal dysfunction suggested by these findings is reversible in these disorders. Elevated glutamate and glutamine (Glx) in patients with bipolar disorder and reduced Glx in patients with unipolar major depression support models of increased and decreased glutamatergic function, respectively, in those conditions. Reduced phosphomonoesters and intracellular pH in bipolar disorder and elevated dynamic lactate responses in panic disorder are consistent with metabolic models of pathogenesis in those disorders. Preliminary findings of an increased glutamine/glutamate ratio and decreased GABA in patients with schizophrenia are consistent with a model of NMDA hypofunction in that disorder. As MRS methods continue to improve, future studies may further advance our understanding of the natural history of psychiatric illnesses, improve our ability to test translational models of pathogenesis, clarify therapeutic mechanisms of action,and allow clinical monitoring of the effects of interventions on brain metabolicmarkers PMID- 22294089 TI - Evaluation of femoral head coverage following Chiari pelvic osteotomy in adolescents by three-dimensional computed tomography and conventional radiography. AB - INTRODUCTION: Currently, the cover of the femoral head was mainly assessed using conventional plain films after Chiari pelvic osteotomy in most studies. The purpose of the current study was to observe whether the femoral head coverage measured by three-dimensional computed tomography (3D-CT) was consistent with the radiographic findings. PATIENTS AND METHODS: A total of 24 patients (24 hips) with an average age of 11.5 years, underwent Chiari osteotomy due to acetabular dysplasia, and 15 subjects (30 hips) of normal control with a mean age of 12 years were involved in the study. The pre- and postoperative coverage of femoral head was measured by using conventional plain film and 3D-CT on the anterior 1/4, middle 1/2, and posterior 1/4 coronal plane. The anterolateral, mediolateral and posterolateral coverage measured by 3D-CT were compared with the coverage measured by plain radiograph, and which were also compared with the normal control individuals. RESULTS: The postoperative anterolateral, mediolateral coverage measured by 3D-CT was significantly smaller than that measured by radiography (P < 0.01). No significant difference was found between the 3D-CT measurements on the posterolateral coverage and the radiographic results. The anterolateral femoral head coverage in the patients following Chiari pelvic osteotomy was also smaller than that in the normal control individuals (P = 0.026). In contrast, the postoperative posterolateral coverage in the patients was more excessive than that in the normal control individuals (P = 0.001). CONCLUSION: Conventional radiographs may show sufficient cover of the femoral head after Chiari osteotomy, whereas in fact, the cover may be not perfect, especially on the anterolateral part. Therefore, the postoperative 3D-CT is beneficial for evaluating the outcome of Chiari osteotomy, especially when the anterolateral coverage o PMID- 22294090 TI - Malunion of the distal radius. AB - Fractures of the distal radius are extremely common injuries, which are steadily becoming a public health issue. One of the most common complications following distal radius fractures is still malunion of the distal radius. This review of the literature surrounding distal radius malunion covers the biomechanics of distal radial malunion, treatment options, indications for surgery, surgical techniques, and results. PMID- 22294091 TI - The direct lateral approach: impact on gait patterns, foot progression angle and pain in comparison with a minimally invasive anterolateral approach. AB - INTRODUCTION: Minimally invasive total hip arthroplasty has been successfully introduced in the past decade. Nevertheless, standard approaches such as the direct lateral approach are still commonly used in orthopaedic surgery due to easy handling, good intra-operative overview and low complication rates. However, a frequent occurrence of fatty atrophy within the anterior third of the gluteus medius muscle has been demonstrated when using the modified direct-lateral approach (mDL), which may be associated with a reduction in function, limitation of internal leg rotation, gait disorders and pain. The question addressed in this study is whether mDL-approach leads to unfavourable changes in foot progression angle (FPA), gait and to more postoperative pain compared with a minimally invasive anterolateral approach (ALMI). METHODS: Thirty patients with primary osteoarthritis of the hip were recruited for this study. All subjects received an uncemented THA (Alloclassic-Zweymuller stem, Allofit Cup, FA Zimmer), 15 through an ALMI-approach and 15 via the mDL-approach. Gait analyses were performed both preoperatively and 3 months after surgery to measure FPA, step length, stance duration, cadence and walking speed. Additionally, the Harris-Hip Score, pain according to the visual analogue scale and the Trendelenburg sign were evaluated. RESULTS: No influence of the surgical approach could be observed on the gait patterns or FPA. Furthermore, neither increased external rotation of the limb nor restriction of internal rotation during walking could be established. Pain and Harris-Hip Score did not diVer significantly between the two groups. CONCLUSION: In comparison with an ALMI approach, the mDL approach did not lead to a change in FPA postoperatively. No detrimental effect could be found on the gait pattern or pain after surgery. Based on these measurements, the minimally invasive anterolateral approach did not appear to provide functional benefits in outcome over the mDL approach. Consequently, both surgical approaches seem to be equally applicable approaches with good to very good functional results. PMID- 22294092 TI - Wide-range protein photo-crosslinking achieved by a genetically encoded N(epsilon)-(benzyloxycarbonyl)lysine derivative with a diazirinyl moiety. AB - A derivative of N(epsilon)-benzyloxycarbonyl-L-lysine with a photo-reactive diazirinyl group, N(epsilon)-[((4-(3-(trifluoromethyl)-3H-diazirin-3 yl)benzyl)oxy)carbonyl]-L-lysine, was site-specifically incorporated into target proteins in mammalian cells. The incorporated photo-crosslinker is able to react not only with residues as distant as about 15 A but also with those in closer proximity, thus enabling "wide-range" photo-crosslinking of proteins. PMID- 22294093 TI - Competing pathways control host resistance to virus via tRNA modification and programmed ribosomal frameshifting. AB - Viral infection depends on a complex interplay between host and viral factors. Here, we link host susceptibility to viral infection to a network encompassing sulfur metabolism, tRNA modification, competitive binding, and programmed ribosomal frameshifting (PRF). We first demonstrate that the iron-sulfur cluster biosynthesis pathway in Escherichia coli exerts a protective effect during lambda phage infection, while a tRNA thiolation pathway enhances viral infection. We show that tRNA(Lys) uridine 34 modification inhibits PRF to influence the ratio of lambda phage proteins gpG and gpGT. Computational modeling and experiments suggest that the role of the iron-sulfur cluster biosynthesis pathway in infection is indirect, via competitive binding of the shared sulfur donor IscS. Based on the universality of many key components of this network, in both the host and the virus, we anticipate that these findings may have broad relevance to understanding other infections, including viral infection of humans. PMID- 22294095 TI - Hypothermia and Ischemic Stroke. AB - OPINION STATEMENT: The use of tissue plasminogen activator (tPA) is the major treatment method for acute ischemic stroke, but it reaches only a very limited number of stroke patients. Although neuroprotectants may be useful in stroke patients in principle, promising animal data have not yet been successfully transferred to stroke patients. However, many arguments favor the successful translation of therapeutic hypothermia (TH) to stroke patients: it is a multimodal method, there is a strong correlation between fever and outcome in stroke patients, and TH has been shown to be beneficial in other kinds of acute brain injury (resuscitation, perinatal asphyxia). In addition, it is useful in controlling intracranial pressure caused by brain edema. So far, available data from clinical studies are not sufficient to recommend TH for the routine treatment of acute ischemic stroke. The quality of trials and the number of stroke patients treated by TH are far too low to prove efficacy or futility, but multicenter randomized controlled clinical trials are on their way. Studies in awake stroke patients will use TH very early in the clinical setting, which implies certain problems. The use of TH in awake individuals requires methods to suppress cold-induced vegetative responses such as shivering and sympathic activation, clinically relevant side effects that need to be monitored and treated carefully. In mass-occupying ischemic stroke, randomized trials will evaluate the neuroprotective effects of controlling edema and intracranial pressure. Because the optimal depth, duration, and methods of cooling are not clear, only large randomized controlled trials will set the baseline from which TH as a neuroprotective therapy can be optimized and brought successfully to stroke patients. PMID- 22294094 TI - Combined experimental and computational analysis of DNA damage signaling reveals context-dependent roles for Erk in apoptosis and G1/S arrest after genotoxic stress. AB - Following DNA damage, cells display complex multi-pathway signaling dynamics that connect cell-cycle arrest and DNA repair in G1, S, or G2/M phase with phenotypic fate decisions made between survival, cell-cycle re-entry and proliferation, permanent cell-cycle arrest, or cell death. How these phenotypic fate decisions are determined remains poorly understood, but must derive from integrating genotoxic stress signals together with inputs from the local microenvironment. To investigate this in a systematic manner, we undertook a quantitative time resolved cell signaling and phenotypic response study in U2OS cells receiving doxorubicin-induced DNA damage in the presence or absence of TNFalpha co treatment; we measured key nodes in a broad set of DNA damage signal transduction pathways along with apoptotic death and cell-cycle regulatory responses. Two relational modeling approaches were then used to identify network-level relationships between signals and cell phenotypic events: a partial least squares regression approach and a complementary new technique which we term 'time interval stepwise regression.' Taken together, the results from these analysis methods revealed complex, cytokine-modulated inter-relationships among multiple signaling pathways following DNA damage, and identified an unexpected context dependent role for Erk in both G1/S arrest and apoptotic cell death following treatment with this commonly used clinical chemotherapeutic drug. PMID- 22294096 TI - Radioiodine remnant ablation in differentiated thyroid cancer after combined endogenous and exogenous TSH stimulation. AB - AIM: Radioiodine remnant ablation (RRA) after (near-)total thyroidectomy (TE) is a key element in patients with differentiated thyroid cancer (DTC). The use of exogenous TSH stimulation (rhTSH) prior to RRA has shown promising results as compared to conventional thyroid hormone withdrawal (THW). As yet, the efficacy of RRA after brief THW and single rhTSH administration has not been assessed. PATIENTS, METHODS: The study sample comprised 147 patients with DTC referred to our center between May 2008 and September 2010. All patients received TE with subsequent RRA. None of these 147 patients had evidence of distant metastasis. 93 patients had endogenous TSH stimulation 4-5 weeks after surgery (group I) and twenty-six received two rhTSH injections (group II). 28 patients were treated with a single rhTSH injection after a brief THW (group III). RRA-Efficacy was assessed three months after therapy by diagnostic whole-body scan and measurement of the tumour marker thyroglobulin (Tg) under TSH stimulation. RESULTS: Three categories of success were defined for remnant ablation. Based on the definition of successful remnant ablation no visible uptake and a Tg <= 2.0 ng/ml (category 1) was seen in 62/93 patients in group I, in 17/26 patients in group II (p = n.s.) and in 12/28 patients in group III (p < 0.05). Visible radioiodine uptake and a Tg <= 2.0 ng/ml (category 2) was seen in 16/28 patients of group III and thus significantly more frequent than in group I (28/93 patients) (p < 0.01). However, patients in group III (16/28 patients) and group II (8/26 patients) showed no significant difference in this category (p = n.s.). Visible radioiodine uptake and a Tg > 2.0 ng/ml (category 3) was found in 3/93 patients in group I and 1/26 patients in group II but in no patient in group III. CONCLUSION: The third strategy of remnant ablation using a single injection of rhTSH after a brief THW period resulted in a significant higher rate of patients with residual uptake in the thyroid bed and a Tg level below 2 ng/ml three months after remnant ablation in comparison to THW. However, the overall efficacy of the third protocol was not significantly different as compared to two rhTSH injections. Under the aspect of the supply shortage of rhTSH the combined endogenous and exogenous TSH stimulation may be an attractive alternative for remnant ablation in differentiated thyroid cancer. PMID- 22294097 TI - On the role of surface charges for homogeneous freezing of supercooled water microdroplets. AB - Charge induced changes in homogeneous freezing rates of water have been proposed to constitute a possible link between the global atmospheric electric circuit and cloud microphysics and thus climate. We report here on high precision measurements of the homogeneous nucleation rate of charged, electro-dynamically levitated single water droplets as a function of their surface charge. No evidence has been found that the homogeneous volume specific ice nucleation rate of supercooled microdroplets is influenced by surface charges in the range between +/-200 elementary charges per MUm(2). It has also been suggested that filamentation in highly electrified liquids can induce freezing at temperatures well above the homogeneous freezing limit. We report here the observation of Coulomb instabilities of highly charged droplets that are accompanied with the formation and ejection of fine filaments from the liquid supercooled droplets. Down to temperatures of 240 K, which is close to the homogeneous freezing limit of uncharged water, no filamentation induced freezing has been detected. At even lower temperatures, the droplets froze before the instability was reached. These findings rule out that filamentation exerts an important influence on ice formation in supercooled water. Combining these findings, we conclude that the surface charges (even at their maximum possible density) have no significant effect on the homogeneous ice nucleation rate of supercooled cloud droplets. PMID- 22294098 TI - Correlation between plasma amino acid profiles and the various stages of hepatitis B infection. AB - The amino acid metabolism in patients with hepatitis B virus (HBV) infection is significantly changed. In this study, we analyzed the relationship between the amino acid profiles and varying clinical stages of HBV infection, and investigated their significance. The plasma amino acid concentrations in 115 patients with HBV infection and 32 healthy donors were detected and analyzed, and the main indicators of liver function were measured. Correlation analysis was performed between the amino acid profiles (Fischer's ratio, branched-chain amino acid to tyrosine ratio [BTR]) and the key indicators of liver function in patients with HBV infection. Fisher's ratio and the BTR of patients with HBV infection was found to differ from that of the healthy controls, and was also found to significantly correlate with the stage of HBV infection. Changes in the BTR were closely related to the level of key indicators of liver function, and a significant relationship was detected between the Fischer's ratio and the BTR (r=0.928, p<0.001). These results suggest that Fischer's ratio and the BTR can indirectly reflect the degree of liver cell injury. Determining and tracking the plasma amino acid profiles could, therefore, be used for the diagnosis, treatment selection, and prognosis of patients with varying stages of HBV infection. PMID- 22294099 TI - Grafted squaramide monoamine nanoparticles as simple systems for sulfate recognition in pure water. AB - New simple systems formed by a chain containing a squaramide function and a quaternised amine group attached to boehmite or silica-coated boehmite nanoparticles are able to discriminate anions in pure water. PMID- 22294101 TI - Planning Curvature-Constrained Paths to Multiple Goals Using Circle Sampling. AB - We present a new sampling-based method for planning optimal, collision-free, curvature-constrained paths for nonholonomic robots to visit multiple goals in any order. Rather than sampling configurations as in standard sampling-based planners, we construct a roadmap by sampling circles of constant curvature and then generating feasible transitions between the sampled circles. We provide a closed-form formula for connecting the sampled circles in 2D and generalize the approach to 3D workspaces. We then formulate the multi-goal planning problem as finding a minimum directed Steiner tree over the roadmap. Since optimally solving the multi-goal planning problem requires exponential time, we propose greedy heuristics to efficiently compute a path that visits multiple goals. We apply the planner in the context of medical needle steering where the needle tip must reach multiple goals in soft tissue, a common requirement for clinical procedures such as biopsies, drug delivery, and brachytherapy cancer treatment. We demonstrate that our multi-goal planner significantly decreases tissue that must be cut when compared to sequential execution of single-goal plans. PMID- 22294100 TI - A role for sphingolipids in the pathophysiology of obesity-induced inflammation. AB - Following the initial discovery that adipose tissue actively synthesizes and secretes cytokines, obesity-induced inflammation has been implicated in the etiology of a host of disease states related to obesity, including cardiovascular disease and type II diabetes. Interestingly, a growing body of evidence similarly implicates sphingolipids as prime instigators in these same diseases. From the recent discovery that obesity-related inflammatory pathways modulate sphingolipid metabolism comes a novel perspective-sphingolipids may act as the dominant mediators of deleterious events stemming from obesity-induced inflammation. This paradigm may identify sphingolipids as an effective target for future therapeutics aimed at ameliorating diseases associated with chronic inflammation. PMID- 22294102 TI - Novel mutations of the HRAS gene and absence of hotspot mutations of the BRAF genes in oral squamous cell carcinoma in a Greek population. AB - Oral squamous cell carcinoma (OSCC) is the sixth most common cancer in the world. The phosphatidylinositol 3 kinase (PI3K) signalling pathway has been reported to play an important role in OSCC. Since we have previously detected absence of hotspot PIK3CA gene mutations in the Greek population, we hypothesized that BRAF or HRAS may be activated as upstream effectors of the pathway. Furthermore, the status of the HRAS and BRAF mutations in OSCC has never been assessed before in the Greek population. Eighty-six primary paraffin-embedded tumors were screened for BRAF and HRAS hotspot mutations. In HRAS, two hotspot mutations in codon 12 (2.3%) and eight new genetic alterations were detected (8.6% overall). One new missense mutation, Alanine53Valine (Ala53Val), one silent mutation, two mutations in the 5'UTR region and four mutations in intron 1 were detected. No hotspot mutations in Braf were found. A new silent mutation/polymorphism T1803C was detected at a percentage of 30%. This study is the first to report HRAS mutations in the Greek population. The results suggest that RAS is an important member of the PI3K signalling pathway and may play a role in the tumorigenesis of OSCC. PMID- 22294103 TI - One-step and rapid synthesis of "clean" and monodisperse dendritic Pt nanoparticles and their high performance toward methanol oxidation and p nitrophenol reduction. AB - Well-defined and monodisperse dendritic platinum nanoparticles (DPNs) are successfully prepared by a rapid, one-step, and efficient route with high yield in aqueous solution, wherein neither organic solvents nor surfactants are employed, ensuring the as-made DPNs definitely have "clean" surfaces, allowing them to exhibit high activity for both methanol oxidation and p-nitrophenol reduction. This proposed strategy for simple and facile preparation of "clean" metal nanocatalysts paves the way for accurately evaluating and further improving their intrinsic catalytic activity. PMID- 22294105 TI - Functional study of immature dendritic cells co-transfected with IL-10 and TGF beta 1 genes in vitro. AB - Dendritic cells (DC) have important functions in T cell immunity and T cell tolerance. Previous studies suggest that immature dendritic cells (imDCs) might be involved in the induction of peripheral T cell tolerance. While interleukin-10 (IL-10) functions at different levels of the immune response, transforming growth factor-beta 1 (TGF-beta 1) is considered to be a key factor in immune tolerance. In this study, we investigated the effects of immature DC (imDC) co-transfected with IL-10 and TGF-beta 1 genes (IL-10-TGF-beta 1-imDC) on inducing immune tolerance. Moreover, we compared the effects of IL-10-TGF-beta 1-imDC with IL-10 transfected imDC (IL-10-imDC) and TGF-beta 1-transfected imDC (TGF-beta 1-imDC), respectively. IL-10-TGF-beta 1-imDC resulted in the down-regulation of MHC class II, CD80 and CD86. IL-10-TGF-beta 1-imDC could induce T cell hyporesponsiveness, and was reluctant to proliferate. IL-10-TGF-beta 1-imDC was more effective than IL-10-imDC and TGF-beta 1-imDC, respectively. In summary, co-expression of IL-10 and TGF-beta 1 affected the immunity of imDCs and enhanced their tolerogenicity. It might be a promising therapy for donor-specific tolerance after organ transplantation. PMID- 22294106 TI - Cytochrome P450 1A1 (CYP1A1) gene polymorphisms and cervical cancer risk: a meta analysis. AB - This meta-analysis aims to examine whether the genotype status of MspI and Ile462Val polymorphisms in Cytochrome-P450 1A1 (CYP1A1) is associated with cervical cancer risk. Eligible case-control studies were identified through search in MEDLINE (end of search: October 2010). Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random effects models. Concerning MspI polymorphism, six studies were eligible (722 cases and 770 controls); four studies were eligible (350 cases and 519 controls) for Ile462Val. MspI polymorphism was associated with elevated cervical cancer risk (for heterozygous TC vs. TT carriers OR = 1.50, 95% CI: 0.93-2.42, random effects; for homozygous CC vs. TT carriers OR = 2.66, 95% CI: 1.14-6.19, random effects). Similarly, Ile462Val polymorphism was associated with elevated cervical cancer risk (for heterozygous Ile/Val vs. Ile/Ile carriers OR = 2.36, 95% CI: 1.10-5.08, random effects; for homozygous Val/Val vs. Ile/Ile carriers OR = 2.73, 95% CI: 1.21 6.15, fixed effects). The results were replicated upon Caucasian subjects, who represented the majority of existing data. The two examined CYP1A1 genotype polymorphisms seem to confer additional risk for cervical cancer. Accumulation of further data seems mandatory for future race-specific analyses and for the demonstration of CYP1A1-smoking interactions. PMID- 22294107 TI - Association between alpha1-antichymotrypsin signal peptide -15A/T polymorphism and the risk of Alzheimer's disease: a meta-analysis. AB - No consensus has been recently reached at the relationship between the alpha1 antichymotrypsin (ACT) signal peptide -15A/T polymorphism and Alzheimer's disease (AD) risk. Thus, our study aimed to better assess this association by performing a meta-analysis, including 4,212 cases and 4,039 controls from 29 studies. Odds ratios (ORs) with the 95% confidence interval (CI) were used to assess the strength of relationship between ACT -15A/T polymorphism and AD risk. Overall, a borderline statistically significant association was detected under recessive model comparison in all subjects (AA vs. AT+TT: OR 1.12, 95% CI 1.01-1.25, P = 0.04). But in subgroup analysis by ethnicity, no significant association was found in Caucasians, Asians, or Africans. Moreover, after exclusion of one study which affect the heterogeneity, the ACT A allele and AA genotype were statistically associated with late-onset AD (LOAD) risk (AA vs. TT: OR 1.25, 95% CI 1.06-1.48, P = 0.007, A vs. T: OR 1.12, 95% CI 1.03-1.21, P = 0.008), especially in Caucasians. In conclusion, our study suggests that the common alpha1-antichymotrypsin signal peptide -15A/T polymorphism may not be a major risk factor for AD. However, the polymorphism is capable of increasing LOAD risk. PMID- 22294104 TI - Analysis of 2,297 expressed sequence tags (ESTs) from a cDNA library of flax (Linum ustitatissimum L.) bark tissue. AB - Bast fibre crops are the second most important natural fibre crops following cotton. Of these, flax (Linum ustitatissimum L.) is the most widely planted in the world, with its fibre used for high quality linen textile. A cDNA library of flax bark tissues was constructed with the purpose of identifying genes involved in the Bast fibre development. A total of 2,297 unigene sequences were obtained from 3,200 randomly selected clones of the cDNA library. These sequences were grouped into 155 clusters and 2,142 singletons, which have been submitted to the GenBank databases. By putative functional annotation, 23.3% of these sequences were similar to known proteins in GenBank, 44.0% of these sequences were similar to unknown proteins, and 32.7% of these sequences showed no significant similarity to any other protein sequences in existing databases. Classified by the Gene Ontology, 24.8, 23.1 and 14.3% were assigned to molecular function, biological process, and cellular component GO terms, respectively. By further bioinformatics approaches, about 110 ESTs matched cell wall related genes in the MAIZEWALL database, representing 16 functional categories of all 19 categories, of which, the most abundant category was protein synthesis. Based on the PlantTFDB database, 39 of the 64 transcription factor families in the Arabidopsis thaliana genome were identified as being involved in flax cell wall formation. The sequences and bioinformatics analysis data generated in this paper will be useful for gene expression, cloning and genetic engineering studies to characterize bast fibre development and improve the properties of the bast fibres. PMID- 22294108 TI - Association of hOGG1 Ser326Cys polymorphism with gastric cancer risk: a meta analysis. AB - Studies investigating the association between human 8-oxoguanine glycosylase 1(hOGG1) Ser326Cys polymorphism and gastric cancer (GC) risk have reported conflicting results. We performed a meta-analysis of published case-control studies to better compare results between studies. 11 eligible studies with 2,180 GC cases and 3,985 controls were selected. There were 5 studies involving Caucasians and 5 studies involving Asians. The combined result based on all studies did not show significant difference in any genetics models. Ser/Cys + Cys/Cys versus Ser/Ser (OR = 0.91, 95% CI 0.81-1.03), Cys/Cys versus Ser/Cys + Ser/Ser (OR = 1.07, 95% CI 0.80-1.44), Ser/Cys versus Ser/Ser (OR = 0.91, 95% CI 0.80-1.03), Sys/Cys versus Ser/Cys (OR = 1.10, 95% CI 0.83-1.47), Cys/Cys versus Ser/Ser (OR = 0.99, 95% CI 0.74-1.34), Cys versus Ser (OR = 1.01, 95% CI 0.88 1.17).When stratifying for ethnicity, there was still no significant association found between hOGG1 Ser326Cys polymorphism and GC risk. Funnel plot and Egger's test showed some evidence of publication bias on the basis of all studies. Two studies were the main reason because their samples were too small. However, the result of sensitivity analysis suggested that the influence of these two studies and one mixed population study on the pooled OR was weak. Our result could explain the association between hOGG1 Ser326Cys polymorphism and GC risk. In conclusion, we did not found the evidence that the Cys allele at codon 326 of hOGG1 could increase GC risk in our analysis. PMID- 22294109 TI - [Assessment of patient care needs in general practice]. AB - OBJECTIVE: In the German health system general practice has changed drastically in the past few years and patients' opportunities to get medical informations have increased significantly. In light of this, patients' needs in general practice should be re-assessed. PATIENTS AND METHODS: 279 patients from 16 practices mainly in Hessen and Rhineland-Palatinate were interviewed. Using principal factor analysis, 51 questions about doctors were analyzed regarding possible dimensions of patient care needs. RESULTS: The dimensions of patient care needs could be described with four scales: (1) social situation and emotional support, (2) the practitioner's expertise, explanations and information, (3) empathy and esteem for patients and (4) availability of the practitioner and care to chronic patients. In older age groups the importance of psychosocial care was emphasized as well as the practitioner's availability and care for patients with chronic diseases. CONCLUSION: Patient care needs are concentrated in four scales, which include psychosocial and continuous care and availability for patients with chronic diseases. These tasks should be further emphasized in medical education and also represented in the remuneration of practitioners. PMID- 22294110 TI - [Histoplasmosis: uncommon opportunistic infection in a patient with HIV infection]. AB - HISTORY AND ADMISSION FINDINGS: A 19-year-old HIV-positive man was admitted with fever of unknown origin and poor general condition. Antiretroviral therapy had been stopped by the patient eight months prior to admission. INVESTIGATIONS: Laboratory tests revealed pancytopenia, high viral load and low count of T-helper cells (13/ul). Computer tomography of the thorax showed small patchy infiltrations. Extensive examinations (microbiology, laboratory tests, multiple investigations) revealed no pathogen. Liver biopsy proved disseminated histoplasmosis. TREATMENT AND COURSE: Liposomal amphotericin B was started and switched to oral itraconazole after 14 days with itraconazole. With this treatment the patient condition improved and fever stopped. T-helper cells increased and the patient was discharged. CONCLUSION: Disseminated histoplasmosis as an AIDS-defining opportunistic infection is uncommon (particularly as the patient had not been abroad in the last four years) and can be a life-threatening complication. Diagnosis must be confirmed by invasive methods especially in patients with compromised immune status and rapid clinical progression. PMID- 22294111 TI - [22-year-old patient in critical care after central venous catheter insertion. Suspected pneumothorax right after insertion of a central venous catheter]. PMID- 22294112 TI - [Is monotherapy with beta-lactam antibiotics still up to date? New aspects for treatment of severe infections]. AB - Mortality of sepsis is still high. Crucial for therapeutic response are the early start of treatment as well as the choice of antibiotics or antibiotic combinations. beta-lactam antibiotics with bactericidal mode of action are often recommended in guidelines. But this antibiotic class can trigger the immune system to a maximum by releasing cell wall components or exotoxins. This may lead to a worsening of the patient's clinical situation. In contrast, antibiotics with bacteriostatic action often inhibit bacterial protein synthesis with decrease of production of virulence factors and minimize release of cell wall components. The purpose of this review is to summarise the significance of some bacteriostatic antibiotics and to discuss whether a combination of bactericidal and bacteriostatic agents may improve the course of the illness. PMID- 22294113 TI - [Peripheral Doppler pressure measurement]. PMID- 22294114 TI - [Elevated augmentation index]. PMID- 22294115 TI - Characterization of neurotensin receptors. AB - This unit describes procedures for performing competition binding assays with neurotensin receptor subtypes 1 and 2 (NTS1 and NTS2). Binding assays using cloned receptors, brain membranes, and primary cultured mesencephalic neurons are presented. NTS1 binding assays employing either radiolabeled neurotensin or SR 48692 (a nonpeptide neurotensin antagonist) as radioligands are described. These procedures may be used to screen selective ligands at neurotensin receptor subtypes. PMID- 22294116 TI - Characterization of CGRP receptor binding. AB - CGRP receptor binding may be measured using homogenates of cell membranes or intact cells. Here a microcentrifugation-based assay is described that utilizes radioiodinated CGRP in displacement studies to determine the binding parameters for any ligand that interacts with CGRP receptors. A similar assay is described for binding to cultured cells. The protocols may be adapted for other radioligands or for filtration-based assays. The main problems with CGRP binding assays can usually be traced to degradation of the radioligand or displacing ligands. Also, some cell lines fail to express CGRP receptors after extensive passage. CGRP binding assays provide a rapid and easy approach for distinguishing between receptors for CGRP and related peptides such as adrenomedullin and amylin. PMID- 22294117 TI - Electrophysiological characterization of recombinant and native P2X receptors. AB - ATP acts as a fast neurotransmitter by activating a family of ligand-gated ion channels, the P2X receptors. Functional homomeric P2X(3) and heteromeric P2X(2/3) receptors are highly localized on primary sensory afferent neurons that transmit nociceptive sensory information. Activation of these P2X(3)-containing channels may provide a specific mechanism whereby ATP, released via synaptic transmission or by cellular injury, elicits pain. The experimental procedures described in this unit are useful for the electorphysiological characterization of P2X receptors. In addition, these protocols provide methods for the evaluation of ligands that interact with P2X receptors that are either natively expressed on excitable cells or cloned and expressed in heterologous cell systems. These methods are derived from standard electrophysiological principles and procedures that are applicable to a wide variety of ligand-gated ion channels. Specific attention is given here to the reliable electrophysiological measurement of both quickly (P2X(3)) and more slowly (P2X(2) and P2X(2/3)) desensitizing receptors. PMID- 22294118 TI - Methods of measuring internalization of G protein-coupled receptors. AB - This unit provides detailed protocols for measuring receptor internalization. The techniques are sufficiently generalized to be applicable to most receptors in a wide variety of cell types. Both radioactive and non-radioactive techniques are described that may be used to quantify receptor internalization, and the differences between the two are highlighted. This unit discusses how quantification of internalization may be achieved, and the advantages and drawbacks of each technique. Low- and higher-throughput methods are compared, and the technologies required to conduct the analyses are discussed. PMID- 22294119 TI - Measurement of VLA-4/CS-1 and VLA-4/VCAM adhesion inhibition. AB - Cell adhesion, a critical early step in the inflammatory process, has increasingly become the target of drug discovery efforts. Described in this unit are techniques for measuring inhibitors of VLA-4-mediated adhesion to either VCAM or the connecting segment (CS-1) of fibronectin. PMID- 22294120 TI - Measurement of cell death in mammalian cells. AB - This unit presents methods used to assess cell death in mammalian cells. The unit is divided into five sections: (1) a brief overview of cytotoxicity and pathways of cell death, (2) an improved method to measure cell death using lactate dehydrogenase (LDH) release as a marker of membrane integrity, (3) a flow cytometry method that simultaneously measures two types of cell death, oncosis and apoptosis, (4) use of nuclear morphology to assess apoptosis and oncosis, and (5) a brief discussion of the use of cytotoxicity assays to determine the mechanisms of cell death. PMID- 22294121 TI - A rat model of postoperative pain. AB - Research on pain resulting from an incision is crucial for developing therapies for postoperative pain, a condition for which effective and inexpensive treatments are not yet available. Because of the gap between preclinical models of persistent pain (e.g., inflammatory, neuropathic) and acute postsurgical pain, efforts have been undertaken to develop methods for studying pain caused by incisions. To this end, a rat model for postoperative pain has been developed. The model uses a plantar incision in the hindpaw and is characterized by persistent, reduced withdrawal thresholds to mechanical stimuli, as is the case in patients after surgery. The pain behaviors are greatest immediately after recovery from anesthesia. The enhanced responsiveness remains remarkable for several days and then gradually decreases. The model is useful for screening test compounds that may be effective in reducing postoperative pain and for understanding pain mechanisms associated with incisions. PMID- 22294122 TI - Models of muscle pain: carrageenan model and acidic saline model. AB - Carrageenan or acidic saline injected unilaterally into the gastrocnemius muscle or triceps muscle produces a robust and long-lasting hyperalgesia in rats and mice, which is reversible with systemic administration of opioid or anti inflammatory drugs. This unit describes detailed protocols for inducing and measuring hyperalgesia, and provides information on validation of these models. These models are useful for assessing new compounds for their analgesic activity in muscular pain. PMID- 22294123 TI - Models of visceral pain: colorectal distension (CRD). AB - The visceromotor response to balloon distension of the colon is a robust behavioral model of visceral nociception in rodents and is ideally suited for studying the visceral antinociceptive activity of drugs. This unit describes, in detail, quantification of this response with the use of electromyography in both rats and mice. PMID- 22294124 TI - Model of attention deficit hyperactivity disorder: five-trial, repeated acquisition inhibitory avoidance in spontaneously hypertensive rat pups. AB - There is no one definitive animal model or test for ADHD. However, behavioral symptoms of this disorder, such as inattentiveness, impulsivity, rate of learning, and hyperactivity, can be evaluated in animals. Unfortunately, many of the cognitive tests used to assess attention and impulsivity require considerable equipment, and financial and time resources. Additionally, many of the genetic animal models are difficult to obtain due to cost, intellectual property issues, or difficulties in breeding sufficient numbers. The spontaneously hypertensive rat (SHR) is relatively easily obtained and exhibits many behavioral abnormalities analogous to those observed in ADHD. This unit describes a cost effective and relatively simple approach to modeling ADHD preclinically, by training juvenile SHR pups in a five-trial repeated acquisition inhibitory avoidance model with components of attention and response inhibition. The model is suited to identifying compounds with stimulant and nonstimulant mechanisms of action, although the latter has yet to be verified conclusively in the clinic. PMID- 22294125 TI - Hepatic clearance and drug metabolism using isolated perfused rat liver. AB - The isolated perfused rat liver (IPRL) has been extensively used as an intact organ model for determination of hepatic clearance and metabolism of drugs. The IPRL model can also be applied to determine physiologically based pharmacokinetics. Since the IPRL model avoids neural and hormonal interferences and excludes influences from absorption processes and non-hepatic elimination routes such as renal excretion and respiration, it provides a relatively clean hepatic system to study metabolism and pharmacokinetics. It is especially useful to model the hepatic uptake associated with plasma protein binding and transport. The viability of the liver can be evaluated based on the gross appearance, bile flow, perfusion pressure, lactate dehydrogenase release, and oxygen uptake. The protocol describes the surgical procedures for isolation of the rat liver, a hemoglobin-free perfusion method, and application of this model for determination of hepatic uptake and clearance. PMID- 22294126 TI - Overview of approaches to the identification of inhibitors of cytokine action. AB - Cytokines are key regulatory molecules that serve as critical mediators of cell to-cell communication. They play a central role in immune function and are important molecular targets for drug discovery because of their dysregulation in immune disease. Initial attempts to develop agents that block the actions of cytokines focused on identifying small-molecule antagonists that would directly compete with these cytokines for their cognate receptors. These efforts were, for the most part, unsuccessful. Outlined in this unit are strategies for developing new approaches. The first section describes strategies for how one might build a conceptual framework to approach this problem. The second section focuses on the technical approaches that can be utilized to accomplish the strategies outlined in the first section. These concepts are illustrated using interleukin-2 (IL-2) as a prototype, since there is a substantial body of knowledge regarding this cytokine, including information on its functions, signaling pathways, and physiological effects in normal and diseased tissue. PMID- 22294127 TI - Primary observation (Irwin) test in rodents for assessing acute toxicity of a test agent and its effects on behavior and physiological function. AB - The Irwin observation test is commonly used to evaluate the effects of a new substance on behavior and physiological function. The results of the Irwin test are used to determine potential toxicity and to select doses for specific therapeutic activity. The Irwin test can also be used in a safety approach for detecting untoward effects of a new compound on general behavior and for evaluating its acute neurotoxicity. In particular, data obtained in the Irwin Test can help to determine the dose range to be tested in other safety tests. Furthermore, the Irwin Test can furnish a first but pertinent orientation towards a specific therapeutic indication, a specific mechanism of action or a specific physiological function. PMID- 22294128 TI - Animal tests of anxiety. AB - Animal tests of anxiety are used to screen novel compounds for anxiolytic or anxiogenic activity, to investigate the neurobiology of anxiety, and to assess the impact of other occurrences such as exposure to predator odors or early rearing experiences. This unit presents protocols for the most commonly used animal tests of anxiety. The Geller-Seifter conflict test, the social interaction test, light/dark exploration, the elevated plus-maze, defensive burying, and the thirsty rat conflict. The protocols are described in terms of drug screening tests, but can be modified easily for other purposes. PMID- 22294129 TI - Overview on the use of therapeutic antibodies in drug discovery. AB - The number of therapeutic antibodies approved by regulatory agencies as novel drugs and the number of antibodies in development has increased significantly. The modular nature of antibody structure has enabled researchers to more predictably design therapeutic antibodies by choosing appropriate functional features most appropriate for a given antibody target and clinical indication. Advances in recombinant antibody technologies have allowed the routine generation of antibodies that can satisfy stringent drug design criteria, such as low immunogenicity, high affinity, target specificity, and commercially viable manufacturing methods. Engineering design opportunities exist for both the variable and the constant regions that encompass, in addition to antigen specificity and affinity, effector functions that mediate immune complex clearance or pharmacokinetics. These are discussed in the context of relevant in vivo and in vitro technologies, such as human IgG transgenic mice, phage display, and biologics manufacturing. Finally, therapeutic antibodies are compared with traditional drugs with respect to target class, selectivity, route of administration, intellectual property issues, and lead discovery and optimization. PMID- 22294130 TI - Mechanochemical reactions of coordination polymers by grinding with KBr. AB - Grinding of a one-dimensional (1-D) ladder coordination polymer (CP), [Zn(MU CH(3)CO(2))(CF(3)CO(2))bpe] (1), and a hydrogen-bonded 1-D CP, [Cd(CH(3)CO(2))(2)bpe(H(2)O)] (2), with KBr resulted in the exchange of carboxylate by bromide ions and the formation of 1-D zigzag and 2-D CPs respectively. PMID- 22294131 TI - miR-200b is involved in intestinal fibrosis of Crohn's disease. AB - Intestinal fibrosis is one of the major serious complications of Crohn's disease (CD). However, there are no effective antifibrotic drugs to treat intestinal fibrosis in CD. Therefore, it is important to understand the pathogenesis of fibrosis in CD. It has been reported that members of the miR-200 family are essential in the regulation of renal fibrogenesis. In this study, we analyzed the function of miR-200a and miR-200b in intestinal fibrosis, which was induced by transforming growth factor beta1 (TGF-beta1) in vitro. Furthermore, we detected the expression of miR-200a and miR-200b in CD specimens, which were divided into groups of fibrosis and no-fibrosis. The results of this study showed that administration of miR-200b could partially protect intestinal epithelial cells from fibrogenesis in vitro. Furthermore, we found that miR-200b was overexpressed in the serum of the fibrosis group. The results suggest that miR-200b has potential value for diagnostic and therapeutic applications for CD patients with fibrosis complications. PMID- 22294134 TI - Acquired dermal melanocytosis induced by psoralen plus ultraviolet A therapy. PMID- 22294135 TI - [SFBC: 70 years of medical biology]. PMID- 22294136 TI - [Analytical quality of assays and comparison of procedures for the sweat test]. AB - Sweat test measuring the chloride ion (Cl(-)) concentration in sweat is a tool for the cystic fibrosis (CF) diagnosis. We evaluated analytical criteria of different available methods and compared them into five hospitals and throught a national quality control program. Sweat tests were performed by stimulation using pilocarpine iontophoresis, sweat collection and measurement of sweat Cl(-) (mmol/L) by titration (colorimetric or coulometric end-point) or by in situ direct potentiometry using a chloride-selective electrode. Indirect determination by sweat conductivity measurement was expressed in mmol/L sodium chloride (NaCl) equivalents (Eq). Linearity range was demonstrated for all measurement procedures in the range 10 to 120 mmol/L. Intra-laboratory coefficients of variation (CVs) were <5% for values between 10 and 100 mmol/L. Inter-laboratory CVs were <3% only for conductivity measurement whatever the range. The comparison of results obtained for a same sweat sample, simultaneously by coulometric and conductivity measurements, demonstrated a first degree linear distribution between 30 to 60 mmol/L Cl(-) allowing us to establish an analytical correspondence table for this range. Thus, calculated values for 30, 40 and 60 mmol/L Cl(-) were respectively 57, 66 and 84 mmol/L NaCl Eq. In conclusion, comparison of methods highlighted that the less the sweat test is automatically controlled, the more the operator influence on results quality is important. Our study supports that sweat test result <50 mmol/L NaCl Eq is unlikely with CF diagnosis in absence of clinical arguments. PMID- 22294137 TI - [Apolipoprotein(a) isoforms immunoblotting detection: comparative study of two methods]. AB - This study reports the comparison between two methods (chemiluminescence and enzymatic colorimetry) for revelation of apolipoprotein(a) [apo(a)] isoforms by immunoblotting in 102 Ivorian healthy subjects. Apo(a) isoform sizes were determined by sodium dodecyl sulfate-agarose-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting using enzymatic colorimetry or chemiluminescence. Within-run precision was comprised between 4.9% and 9.2% for colorimetry and between 2.9% and 4.6% for chemiluminescence. Both methods have detected apo(a) isoforms in all patients, even when lipoprotein(a) concentrations were under detection limit (0.02 g/L). The two methods were significantly correlated (r = 0.96 to 0.98, p<0.0001). Even though the chemiluminescence method exhibited better performances than the colorimetric method, both techniques could be used indifferently. PMID- 22294138 TI - [Sensitization to aeroallergens at Mohamed V Hospital (Rabat, Morroco)]. AB - This transversal case study aimed at drawing the biological profile of sensitized patients consulting for respiratory allergies at Mohamed V Military Hospital Rabat. One hundred four patients were included in the case study, who have benefitted from specialized medical consultation and those who came to the biochemistry laboratory holding a medical check-up prescription for allergy (NFS and biochemical check-up). The biochemical analysis were made up of TMA Phadiatop((r)), correct proportioning of specific IgE serum, and complete IgE. The different anamnestic and clinical parameters acting upon the sensitization to respiratory allergens have been collected through a multiple choice question survey. Statistical analysis has been performed by a SPSS software version 13.0. The Phadiatop((r)) was positive at 54.8% of our patients with a masculine predominance (H/F sex-ratio = 1.4). The recurring symptoms were the rhinitis (36.8%) and the asthma (10.5%). The allergen d1 Dermatophagoides pteronyssinus was the most incriminated pneumallergens (59.6%). For 19.3% of the patients sensitized, a polysensitization (superior to three) was noted, due to dust mite, cockroaches, pollen and animals. 93.6% of the Phadiatop((r)) positive patient had a hypereosinophilia (p < 0.001). The complete IgE had been prescribed to 29 patients and had been increased among 19 patients in 66% of the cases. Among the patients having a rate of elevated complete IgE, 8 (42.1%) had a negative Phadiatop((r)) (p = 0.019). Our survey showed the strong prevalence of the respiratory sensitization at our population. The allergen d1 is the most incriminated. It also put in evidence the weak diagnostic value of the dosage of the complete IgE in the respiratory allergy. PMID- 22294139 TI - [Pseudocholinesterase activity in type 1 bipolar patients]. AB - This study aims to investigate the variation of pseudocholinesterase activity (BuChE) in bipolar patients and to explore its relation to the clinical and therapeutic characteristics of this disease. Our study included 105 patients with bipolar disorder and 100 control subjects aged 38.7 +/- 12.2 and 36.4 +/- 15.7 y, respectively. BuChE was determined by kinetic methods on Cobas Integra 400 plusTM. Compared with controls, patients had a significantly higher pseudocholinesterase activity. Moreover, this increase was significantly associated (p = 0.001) with bipolar disorder with sensibility of 58% and specificity of 62% at threshold of 7392 IU/L. There was no significant change in pseudocholinesterase activity in relation to illness episodes and treatment, whereas the lowest values of this activity were seen in euthymic patients and those taking psychotics. Therefore, this activity is a real interest in the biological monitoring of patients as a risk factor for neurodegenerative diseases associated with bipolar disorder. But it would be most useful to evaluate their interest as a predictor of bipolar disorder in patients at risk. PMID- 22294140 TI - [Biological assay for galactose-1 phosphate measurement application in subjects with galactosemia]. AB - Congenital galactosemia is a hereditary, autosomal recessive and metabolic disease. It is linked to an enzyme deficiency, more commonly known by the deficiency of galactose-1- phosphate uridyltransferase (GALT), which is responsible for an accumulation of galactose-1- phosphate in the blood. Clinical symptoms appear early in infancy from the second week of life. They generally manifested by some disorders within liver, kidney, eye, gastrointestinal, neurological and also with cataracts. Currently, the clinical diagnosis remains difficult hence the importance of further investigations based on effective biological assessments to highlight the disease. The diagnosis of galactosemia is made by the laboratory test. The latter includes the determination of Gal-1-P which is done by a fluorometric method spot test. This study was conducted in order to assess the repeatability, reproducibility, accuracy, and effectiveness of the techniques used. We have found the CV for a repeatability (CV = 5 %), reproducibility (CV = 4 %) which confirms the accuracy of the method proceeded in this study. This method allows us to have a degree of inaccuracy less than 1%. According to the study of the effectiveness of "spot test", we found that our technique is specific (Sp = 93 %) and sensitive (Se = 83 %). PMID- 22294141 TI - [Triple fungal infection in a patient with liver cirrhosis]. AB - The prevalence of invasive mycoses is increasing, especially among patients who are immunocompromised or hospitalized with serious underlying diseases. Such infections are associated with a high morbidity and significant mortality, requiring early diagnosis and appropriate treatment but also an optimal prophylaxis in patients with high risk factors. We report a case of triple fungal infection including an invasive pulmonary aspergillosis by Aspergillus fumigatus, a candidemia by Candida albicans and a Pneumocystis pneumonia. The overall clinical picture of this patient was liver cirrhosis with medical history of immunosuppressive treatment for Crohn disease and a non-hodgkin lymphoma. There was no antifungal prophylaxis for this patient. Under treatment, the issue was unfavourable with multivisceral failure. PMID- 22294142 TI - [Primary granulocytic sarcoma of the peritoneum: a case report and literature review]. AB - Granulocytic sarcoma is a rare tumor composed of immature granulocytic cells. Prognosis is poor. The periosteum is preferentially involved. A peritoneum localization is unusual. We report the case of a 20 years old man without particular previous pathologies, which brutally presented an ascitic syndrome in a context of health impairment state. The laparoscopy showes many white nodules on all the peritoneum. The histologic examination of one of these nodules showed granulocytic sarcoma. The blood and bone marrow cell count are without any anomaly. The treatment consisted of a standard acute myeloid leukaemia's chemotherapy with very good evolution. The rarity of peritoneal chloroma causes a diagnostic problem, especially in the absence of hematologic abnormalities. It must be mentioned in the presence of peritoneal nodules even if the blood count and bone marrow are normal. PMID- 22294143 TI - [Post-varicella cerebral thrombophlebitis with anti-protein S: report of a pediatric case]. AB - Purpura fulminans and venous thrombosis are rare complications of chickenpox. We report the case of a 6 year old with no history individuals who experienced cerebral thrombophlebitis, 3 weeks after varicella. MRI, performed at admission, has objectified longitudinal sinus thrombosis and a frontal parenchymal hematoma law. Meanwhile, a recent varicella seroconversion was demonstrated. The assessment of thrombophilia, meanwhile, has objectified a significant decrease in free protein S and activity, without associated DIC. Origin acquired this deficit was confirmed by the detection of antibodies (IgG and IgM) against the total protein S by ELISA. After evaluation of the benefit/risk only anticoagulation was initiated. The clinical and biological evolution was favorable, with rapid normalization of the S protein and decrease of anti-protein S. Many studies report the presence of anti-protein S in young children at the waning of chickenpox, without their exact frequency is determined. The decrease in protein S they cause leads to a transient hypercoagulable state may result in different clinical pictures. Cases of purpura fulminans seem more frequent when venous thrombosis isolated post chickenpox, sometimes atypical, appear rare. PMID- 22294144 TI - [Association between the percentages of typical forms, acrosome abnormalities and the multiple anomalies indices: potential quality indicators?]. AB - In addition to NF EN ISO 15189, the second version of "GBEA AMP", published in the official journal of the French Republic, had set for "AMP" exams, the actions to be implemented in order to achieve an efficient quality management system. As part of continuous improvement of quality, and besides our external and internal quality systems, we have been developping indicators that will allow an early detection of potential drifts within operators performing sperm morphology testing. We have extracted nearly 1900 sperm morphology tests from our database. These tests were performed by three operators. The analysis of the data collected has shown a cross correlation between the percentages of typical forms, malformative acrosomes and "MAI". We have been using these correlations as quality indicators in our laboratory in order to highlight any potential drift in reading sperm morphology tests. PMID- 22294146 TI - DNA methylation in the human placenta and fetal growth (review). AB - Throughout in utero development, the placenta plays a key role in controlling growth and development. The placenta acts not only as a gatekeeper of nutrient and waste exchange between mother and developing fetus, but also as a regulator of the intrauterine environment. Its functions can be influenced by the environment encountered throughout pregnancy, thereby altering the appropriate genetic programming needed to allow for appropriate fetal growth. Epigenetic alterations related to environmental exposures have been linked to aberrant fetal growth. DNA methylation, which is the best known DNA epigenetic modification, may provide an attractive mechanism linking environmental cues to placental pathology, with consequences for fetal growth and adult life. Alteration of the methylation patterns of genes expressed in the placenta has recently been found to modify gene expression and subsequently impair function of the placenta. Although there is strong evidence to demonstrate that the environment can affect the pattern of DNA methylation of the placenta during fetal development, a direct association between environmental conditions, methylation alterations and gene expression is difficult to confirm. DNA methylation in the placenta has mainly been investigated in the context of imprinted and non-imprinted genes transcription. Several environmental factors have also been assessed in regard to their association with changes to the epigenetic motives of embryonic and extraembryonic tissues and their impact on pregnancy outcome. In this review, we briefly present the available evidence regarding the role of DNA methylation patterns of the placenta on aberrant fetal growth. PMID- 22294147 TI - Nonmyeloablative conditioning regimen to increase engraftment of gene-modified hematopoietic stem cells in young rhesus monkeys. AB - Immune responses to transgene products may lead to rejection of transduced cells, limiting successful gene therapy for genetic diseases. While moderate dosages of chemotherapeutic agents such as busulfan may increase hematopoietic stem cells (HSC) engraftment, they are not immune suppressive and do not abrogate immune responses to transgene products. Studies focused on nonmyeloablative conditioning with busulfan +/- fludarabine in a clinically relevant monkey model to induce immune suppression to allow cells expressing a foreign transgene product to persist. Bone marrow CD34(+) HSC were transduced in two equal fractions using simian immunodeficiency virus (SIV)-based lentiviral vectors carrying a nonexpressed DNA sequence tag (NoN) and the green fluorescent protein (GFP) reporter gene. Post-transplant there was no evidence of elimination of cells containing the potentially immunogenic GFP gene; several recipients had stable persistence of cells, and no differences were detected with fludarabine, which was rapidly cleared. Antibodies and cellular immune responses to GFP developed in recipients with the highest levels of GFP-marked cells, although these cells were not eliminated. These studies establish a clinically relevant pediatric primate model to assess the effects of conditioning regimens on the engraftment of transduced HSC and the immune responses to cells expressing a foreign gene product. PMID- 22294148 TI - Stanniocalcin-1 rescued photoreceptor degeneration in two rat models of inherited retinal degeneration. AB - Oxidative stress and photoreceptor apoptosis are prominent features of many forms of retinal degeneration (RD) for which there are currently no effective therapies. We previously observed that mesenchymal stem/stromal cells reduce apoptosis by being activated to secrete stanniocalcin-1 (STC-1), a multifunctional protein that reduces oxidative stress by upregulating mitochondrial uncoupling protein-2 (UCP-2). Therefore, we tested the hypothesis that intravitreal injection of STC-1 can rescue photoreceptors. We first tested STC-1 in the rhodopsin transgenic rat characterized by rapid photoreceptor loss. Intravitreal STC-1 decreased the loss of photoreceptor nuclei and transcripts and resulted in measurable retinal function when none is otherwise present in this rapid degeneration. We then tested STC-1 in the Royal College of Surgeons (RCS) rat characterized by a slower photoreceptor degeneration. Intravitreal STC-1 reduced the number of pyknotic nuclei in photoreceptors, delayed the loss of photoreceptor transcripts, and improved function of rod photoreceptors. Additionally, STC-1 upregulated UCP-2 and decreased levels of two protein adducts generated by reactive oxygen species (ROS). Microarrays from the two models demonstrated that STC-1 upregulated expression of a similar profile of genes for retinal development and function. The results suggested that intravitreal STC-1 is a promising therapy for various forms of RD including retinitis pigmentosa and atrophic age-related macular degeneration (AMD). PMID- 22294149 TI - Adenovirus-mediated E2-EPF UCP gene transfer prevents autoamputation in a mouse model of hindlimb ischemia. AB - E2-EPF ubiquitin carrier protein (UCP) stabilizes hypoxia-inducible factor-1alpha (HIF-1alpha) inducing ischemic vascular responses. Here, we investigated the effect of UCP gene transfer on therapeutic angiogenesis. Adenovirus-encoded UCP (Ad-F-UCP) increased the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) in cells and mice. Conditioned media from UCP-overexpressing cells promoted proliferation, tubule formation, and invasion of human umbilical-vascular-endothelial cells (HUVECs), and vascularization in chorioallantoic membrane (CAM) assay. Ad-F-UCP increased the vessel density in the Martigel plug assay, and generated copious vessel-like structures in the explanted muscle. The UCP effect on angiogenesis was dependent on VEGF and FGF-2. In mouse hindlimb ischemia model (N = 30/group), autoamputation (limb loss) occurred in 87% and 68% of the mice with saline and Ad encoding beta galactosidase (Ad-LacZ), respectively, whereas only 23% of the mice injected with Ad-F-UCP showed autoamputation after 21 days of treatment. Ad-F-UCP increased protein levels of HIF-1alpha, platelet-endothelial cell adhesion molecule-1 (PECAM-1), smooth muscle cell actin (SMA) in the ischemic muscle, and augmented blood vessels doubly positive for PECAM-1 and SMA. Consequently, UCP gene transfer prevented muscle degeneration and autoamputation of ischemic limb. The results suggest that E2-EPF UCP may be a target for therapeutic angiogenesis. PMID- 22294150 TI - Design of a single AAV vector for coexpression of TH and GCH1 to establish continuous DOPA synthesis in a rat model of Parkinson's disease. AB - Preclinical efficacy of continuous delivery of 3,4-dihydroxyphenylalanine (DOPA) with adeno-associated viral (AAV) vectors has recently been documented in animal models of Parkinson's disease (PD). So far, all studies have utilized a mix of two monocistronic vectors expressing either of the two genes, tyrosine hydroxylase (TH) and GTP cyclohydrolase-1 (GCH1), needed for DOPA production. Here, we present a novel vector design that enables efficient DOPA production from a single AAV vector in rats with complete unilateral dopamine (DA) lesions. Functional efficacy was assessed with drug-induced and spontaneous motor behavioral tests where vector-treated animals showed near complete and stable recovery within 1 month. Recovery of motor function was associated with restoration of extracellular DA levels as assessed by online microdialysis. Histological analysis showed robust transgene expression not only in the striatum but also in overlying cortical areas. In globus pallidus, we noted loss of NeuN staining, which might be due to different sensitivity in neuronal populations to transgene expression. Taken together, we present a single AAV vector design that result in efficient DOPA production and wide-spread transduction. This is a favorable starting point for continued translation toward a therapeutic application, although future studies need to carefully review target region, vector spread and dilution with this approach. PMID- 22294151 TI - HIV develops indirect cross-resistance to combinatorial RNAi targeting two distinct and spatially distant sites. AB - Resistance to existing HIV therapies is an increasing problem, and alternative treatments are urgently needed. RNA interference (RNAi), an innate mechanism for sequence-specific gene silencing, can be harnessed therapeutically to treat viral infections, yet viral resistance can still emerge. Here, we demonstrate that HIV can develop indirect resistance to individual and combinatorial RNAi-targeting protein-coding regions up to 5,500 nucleotides (nt) downstream of the viral promoter. We identify several variants harboring mutations in the HIV promoter, and not within the RNAi targets, that produce more fully elongated transcripts. Furthermore, these variants are resistant to the RNAi, potentially by stoichiometrically overwhelming this cellular mechanism. Alarmingly, virus resistant to one short hairpin RNA (shRNA) also exhibits cross-resistance to a different shRNA, which targets a distinct and spatially distant region to which the virus has not been previously exposed. To our knowledge, this is the first example of HIV "cross-resistance" to viral inhibitors targeting different loci. Finally, combining anti-HIV RNAi with a small molecule enhancer of RNAi can inhibit the replication of an indirectly resistant mutant. These results suggest that indirect resistance to RNAi is a general mechanism that should be considered when investigating viral resistance and designing combinatorial RNAi therapies. PMID- 22294152 TI - Facile synthesis of polypyrrole coated copper nanowires: a new concept to engineered core-shell structures. AB - Polypyrrole coated copper nanowires were synthesized in a one-pot manner in the presence of cupric precursor and pyrrole. They displayed ultra-high sensitivity as a potentiometric sensor with considerable environmental stability comparable to noble metals. PMID- 22294153 TI - Magnesium deficiency results in damage of nitrogen and carbon cross-talk of maize and improvement by cerium addition. AB - Magnesium (Mg) deficiency has been reported to affect plant photosynthesis and growth, and cerium (Ce) was considered to be able to improve plant growth. However, the mechanisms of Mg deficiency and Ce on plant growth remain poorly understood. The main aim of this work is to identify whether or not Mg deprivation affects the interdependent nitrogen and carbon assimilations in the maize leaves and whether or not Ce modulates the assimilations in the maize leaves under Mg deficiency. Maize plants were cultivated in Hoagland's solution. They were subjected to Mg deficiency and to cerium chloride administration in the Mg-present Hoagland's media and Mg-deficient Hoagland's media.After 2 weeks,we measured chlorophyll (Chl) a fluorescence and the activities of nitrate reductase (NR), sucrose-phosphate synthase(SPS), and phosphoenolpyruvate carboxylase (PEPCase)in metabolic checkpoints coordinating primary nitrogen and carbon assimilations in the maize leaves. The results showed that Mg deficiency significantly inhibited plant growth and decreased the activities of NR, SPS, and PEPCase and the synthesis of Chl and protein. Mg deprivation in maize also significantly decreased the oxygen evolution, electron transport,and efficiency of photochemical energy conversion by photosystem II (PSII). However, Ce addition may promote nitrogen and carbon assimilations, increase PSII activities,and improve maize growth under Mg deficiency. Moreover,our findings would help promote usage of Mg or Ce fertilizers in maize production. PMID- 22294154 TI - Increased basic fibroblast growth factor release and proliferation in xenotransplanted squamous cell carcinoma after combined irradiation/anti-vascular endothelial growth factor treatment. AB - Novel strategies of cancer therapy combine irradiation and anti-angiogenic active compounds. However, little is known concerning the undesired cellular and molecular effects caused by this novel treatment concept. We used a mouse squamous cell carcinoma (SCC) xenotransplantation model to evaluate the potential undesired effects which compromise the success of this therapeutic combination. SCCs were subcutanously implanted in nude mice. Animals were treated with a fractionated irradiation scheme (5x4 Gy) alone or in combination with daily injections of anti-vascular endothelial growth factor (VEGF) antibodies. Controls remained untreated. Before and after treatment, resonance imaging (MRI), ultrasound and near-infrared spectrometry were used to evaluate tumor vessel integrity. Finally, tumors were explanted and VEGF, basic fibroblast growth factor (bFGF), vessel density, proliferation and apoptotic activity were analyzed by immunohistochemistry. Irradiation caused VEGF release and we found evidence for VEGF-mediated vessel protection. In the tumors derived from the combined treatment, blood volume was decreased, and apoptotic indices were increased. Remarkably, bFGF levels and proliferative indices were also increased. Combined irradiation/anti-VEGF treatment resulted in the desired VEGF depletion and increased tumor cell apoptosis. Nonetheless, bFGF and proliferation also increased, possibly suggesting a compensatory response. The application of additional targeted drugs may help develop more effective SCC treatments. PMID- 22294155 TI - Dynamics of H2 dissociation on the 1/2 ML c(2 * 2)-Ti/Al(100) surface. AB - The dissociation of H(2) on Ti-covered Al surfaces is relevant to the rehydrogenation and dehydrogenation of the NaAlH(4) hydrogen storage material. The energetically most stable structure for a 1/2 monolayer of Ti deposited on the Al(100) surface has the Ti atoms in the second layer with a c(2 * 2) structure, as has been confirmed by both low-energy electron diffraction and low energy ion scattering experiments and density functional theory studies. In this work, we investigate the dynamics of H(2) dissociation on a slab model of this Ti/Al(100) surface. Two six-dimensional potential energy surfaces (PESs) have been built for this H(2) + Ti/Al(100) system, based on the density functional theory PW91 and RPBE exchange-correlation functionals. In the PW91 (RPBE) PES, the lowest H(2) dissociation barrier is found to be 0.65 (0.84) eV, with the minimum energy path occurring for H(2) dissociating above the bridge to top sites. Using both PESs, H(2) dissociation probabilities are calculated using the classical trajectory (CT), the quasi-classical trajectory (QCT), and the time dependent wave-packet methods. We find that the QCT H(2) dissociation probabilities are in good agreement with the quantum dynamics results in the collision energy range studied up to 1.0 eV. We have also performed molecular beam simulations and present predictions for molecular beam experiments. Our molecular beam simulations show that H(2) dissociation on the 1/2 ML Ti/Al(100) surface is an activated process, and the reaction probability is found to be 6.9% for the PW91 functional and 1.8% for the RPBE at a nozzle temperature of 1700 K. Finally, we have also calculated H(2) dissociation rate constants by applying transition state theory and the QCT method, which could be relevant to modeling Ti-catalyzed rehydrogenation and dehydrogenation of NaAlH(4). PMID- 22294156 TI - Human tau may modify glucocorticoids-mediated regulation of cAMP-dependent kinase and phosphorylated cAMP response element binding protein. AB - Phosphorylation of the cAMP response element binding protein (CREB) by cAMP dependent kinase (PKA) is critical to memory formation. However, activation of PKA can also increase tau phosphorylation, which may contribute to memory impairment. Therefore, the regulation of PKA may be part of the mechanism by which glucocorticoids (GCs) influence memory. Additionally, the cellular response to GCs may be affected by the presence of human tau. The goal of this paper was to study GCs-mediated regulation of PKA as well as CREB and tau phosphorylation in wild-type HEK293 cells and HEK293 cells stably expressing human tau441 (HEK293/tau441 cells). By using dexamethasone (DEX) as GCs, we found that DEX induced a tau-dependent selective decrease in the level of PKA RIIbeta subunit protein. The observed decrease in RIIbeta expression was not due to alterations of mRNA levels and was reversed by inhibiting the proteasome with lactacystin. Moreover, the decrease in RIIbeta did not diminish the co-localization of the catalytic subunit of PKA with tau and might contribute to the DEX-induced increase in tau phosphorylation at Ser-214. DEX also induced a tau-dependent decrease in CREB phosphorylation that could not be reversed by activating PKA with forskolin. Taken together, these results show that human tau protein may alter the GCs-mediated regulation of PKA activity and CREB phosphorylation. PMID- 22294157 TI - Single-prolonged stress induce changes of CaM/CaMKIIalpha in the rats of dorsal raphe nucleus. AB - Ca2+/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) is identified as a Ca2+-dependent kinase in brain involved in the activation of Tryptophan hydroxylase (TPH) acting through direct phosphorylation of TPH, and playing key roles in the signaling pathways initiated by various G protein-coupled 5-HT receptors. The goal of this study is to detect whether there are changes of CaM and CaMKIIalpha in dorsal raphe nucleus in the rats exposed to single-prolonged stress (SPS), which is a model employed in post-traumatic stress disorder (PTSD) study extensively. A total of 90 male Wistar rats were randomly divided into a normal control group and SPS groups of 7d, 14d. The changes of CaM/CaMKIIalpha were detected by immunohistochemistry, reverse transcription-polymerase chain reaction and western blot. Our results demonstrate that both expressions of CaM and CaMKIIalpha significantly increase (P < 0.001) in the SPS 7d group than that in the control group, and then decreased dramatically (P < 0.001) 14 days after SPS. Our results confirm that SPS induce changes of CaM/CaMKIIalpha in the dorsal raphe nucleus. Changes of CaM/CaMKIIalpha may be associated with the activation of 5-HT1A receptor, and may contribute to the progress of molecular mechanism of PTSD. PMID- 22294158 TI - How to manage HIV-infected patients with chronic kidney disease in the HAART era. AB - As human immunodeficiency virus (HIV)-infected patients now live longer while receiving highly active antiretroviral therapy (HAART), chronic kidney disease (CKD) has emerged as a significant cause of morbidity and mortality among urban HIV population. Risk factors associated with CKD in such HIV-infected population include aging, hypertension, diabetes mellitus, co-infection with hepatitis C virus, low CD4 cell count, and high HIV viral load. Clinical experience has shown that HIV-infected individuals often have one or more concurrent risk factors for CKD. The cumulative effect of multiple risk factors on the development of CKD should be noted in this population. Glomerular disease directly related to HIV infection, so-called HIV-associated nephropathy, remains an important cause of CKD among limited HIV population of African descent. The impact of exposure to nephrotoxic antiretroviral agents on the development of kidney disease is both an old and a new concern. In particular, the association of tenofovir with kidney disease has been an area of great interest. The findings regarding tenofovir's adverse effect on long-term kidney function vary among studies. Early identification and treatment of kidney disease is imperative for reducing the burden of patients requiring dialysis in HIV-infected populations. Periodic monitoring of urinary albumin excretion, tubular parameters such as low-molecular weight proteinuria, and the estimated glomerular filtration rate may be useful for early diagnosis of patients at risk for incident CKD. This review focuses on recent developments in epidemiology, risk factors, identification, estimation, and management of CKD in HIV-infected population in the HAART era. PMID- 22294159 TI - Effect of heterozygous deletion of WNK1 on the WNK-OSR1/ SPAK-NCC/NKCC1/NKCC2 signal cascade in the kidney and blood vessels. AB - BACKGROUND: We found that a mechanism of hypertension in pseudohypoaldosteronism type II (PHAII) caused by a WNK4 missense mutation (D561A) was activation of the WNK-OSR1/SPAK-NCC signal cascade. However, the pathogenic effect of intronic deletions in WNK1 genes also observed in PHAII patients remains unclear. To understand the pathophysiological roles of WNK1 in vivo, WNK1(+/-)mice have been analyzed, because homozygous WNK1 knockout is embryonic lethal. Although WNK1(+/ ) mice have been reported to have hypotension, detailed analyses of the WNK signal cascade in the kidney and other organs of WNK1(+/-) mice have not been performed. METHOD: We assess the effect of heterozygous deletion of WNK1 on the WNK-OSR1/SPAK-NCC/NKCC1/NKCC2 signal cascade in the kidney and blood vessels. RESULTS: Contrary to the previous report, the blood pressure of WNK1(+/-) mice was not decreased, even under a low-salt diet. Under a WNK4(D561A/+) background, the heterozygous deletion of the WNK1 gene did not reduce the high blood pressure either. We then evaluated the phosphorylation status of OSR1, SPAK, NCC, NKCC1, and NKCC2 in the kidney, but no significant decrease in the phosphorylation was observed in WNK1(+/-) mice or WNK1(+/-)WNK4(D561A/+) mice. In contrast, a significant decrease in NKCC1 phosphorylation in the aorta and a decreased pressure-induced myogenic response in the mesenteric arteries were observed in WNK1(+/-) mice. CONCLUSION: The contribution of WNK1 to total WNK kinase activity in the kidney may be small, but that WNK1 may play a substantial role in the regulation of blood pressure in the arteries. PMID- 22294160 TI - Enhanced Li storage performance of ordered mesoporous MoO2 via tungsten doping. AB - Ordered mesoporous tungsten-doped MoO(2) was synthesized by a nanocasting method. The Li storage performance of mesoporous MoO(2) is significantly improved by tungsten doping, which exhibits a reversible capacity of 700 mA h g(-1), better cycling and rate performance. This material combines the advantages of the high theoretical capacity of MoO(2) and the better electroactivity of WO(2). PMID- 22294161 TI - Circular permutation of the starch-binding domain: inversion of ligand selectivity with increased affinity. AB - Proteins containing starch-binding domains (SBDs) are used in a variety of scientific and technological applications. A circularly permutated SBD (CP90) with improved affinity and selectivity toward longer-chain carbohydrates was synthesized, suggesting that a new starch-binding protein may be developed for specific scientific and industrial applications. PMID- 22294162 TI - Oridonin induces apoptosis and senescence by increasing hydrogen peroxide and glutathione depletion in colorectal cancer cells. AB - We recently demonstrated that oridonin could induce apoptosis and senescence of colon cancer cells in vitro and in vivo. However, the underlying mechanism remains unknown. In this study, the involvement of reactive oxygen species in oridonin-induced cell death and senescence was investigated in colon adenocarcinoma-derived SW1116 cells. Oridonin increased intracellular hydrogen peroxide levels and reduced the glutathione content in a dose-dependent manner. N acetylcysteine, a reactive oxygen species scavenger, not only blocked the oridonin-induced increase in hydrogen peroxide and glutathione depletion, but also blocked apoptosis and senescence induced by oridonin, as evidenced by the decrease in Annexin V and senescence-associated beta-galactosidase- positive cells and the inhibition of oridonin-induced upregulation of p53 and p16 and downregulation of c-Myc. Moreover, exogenous catalase could inhibit the increase in hydrogen peroxide and apoptosis induced by oridonin, but not the glutathione depletion and senescence. Furthermore, thioredoxin reductase (TrxR) activity was reduced by oridonin in vitro and in cells, which may cause the increase in hydrogen peroxide. In conclusion, the increase in hydrogen peroxide and glutathione depletion account for oridonin-induced apoptosis and senescence in colorectal cancer cells, and TrxR inhibition is involved in this process. Given the importance of TrxR as a novel cancer target in colon cancer, oridonin would be a promising clinical candidate. The mechanism of oridonin-induced inhibition of TrxR warrants further investigation. PMID- 22294163 TI - Receptors as drug targets. AB - Receptors, located on both the cell surface and within the cell, are the molecular targets through which drugs produce their beneficial effects in various disease states. Receptors were initially conceptualized at the beginning of the 20th century by the parallel efforts of Ehrlich and Langley. The concepts of the receptor and receptor theory, based on the Law of Mass Action, have undergone continuous refinement as they have been characterized in terms of their molecular structure, association with ancillary proteins (e.g., G proteins, arrestins, RAMPs), and functional characteristics in normal and diseased tissues. The concepts describing ligand interactions with receptors have also been refined from the simple binary concept of competitive agonists and antagonists to partial agonists, allosteric modulators and inverse agonists. Concepts such as receptor constitutive activity, internalization and dimerization add additional complexity to the role of receptors in tissue function and in precisely characterizing their role in homeostasis and disease. PMID- 22294164 TI - Benzodiazepine binding to GABA(A) receptors. AB - This unit describes ligand binding assays for the characterization of the benzodiazepine (BZ) site of GABA(A) receptors in the central nervous system. The Basic Protocol provides a procedure for analyzing benzodiazepine binding to GABA(A) receptors from brain. The experimental design of the method is suitable for all commercially available radioligands that interact with the BZ site of central GABA(A) receptors. By using the appropriate radioligand in combination with particular displacer compounds, individual (or groups of) GABA(A) receptor subtypes can be identified. Preparation of membrane suspensions for this procedure is described in a Support Protocol, and five Alternate Protocols are provided for the identification of diazepam-sensitive GABA(A) receptors, the alpha1-subtype of diazepam-sensitive receptors, the alpha5 subtype of diazepam sensitive receptors, both diazepam-sensitive and diazepam-insensitive receptors, and diazepam-insensitive receptors exclusively. Each protocol contains a brief description of the requirements for radioligand binding to these five types of BZ sites. PMID- 22294165 TI - Practical aspects of radioligand binding. AB - Radioligand binding has been used for many years to identify new binding sites, characterize receptors, and identify novel ligands. Although various techniques have been developed to improve the efficiency of preparing the biological source of the receptors and for detecting bound radioligand, the principles of the assays remain the same. This unit reviews theory and provides examples of the parameters that can be calculated from radioligand binding data to characterize ligand-receptor interactions. The important aspects of assay development and validation that allow meaningful interpretation are discussed. The selection of a radioligand, buffer and other assay components is critical to developing a useful binding assay. The nature of the binding interaction can also be probed by varying assay conditions. PMID- 22294166 TI - Overview of safety pharmacology. AB - Safety pharmacology assesses the potential risks of novel pharmaceuticals for human use. ICH S7A guidelines recommend a core battery of studies on three vital systems: central nervous system (CNS), cardiovascular (CV) and respiratory. Primary CNS studies look for effects on general behavior, locomotion, neuromuscular coordination, the convulsive threshold, and vigilance. The primary CV test battery evaluates proarrhythmic risk using in vitro approaches (hERG channel and Purkinje fiber assays) and in vivo measurements in conscious animals via telemetry. Comprehensive cardiac risk assessment also includes full hemodynamic evaluation, most suitably conducted in the anesthetized large animal. Basic respiratory function can be approached via whole-body plethysmography in conscious animals where sensitivity to respiratory-depressant effects can be enhanced by exposure to increased CO(2). Other aspects of safety pharmacology studies discussed are the timing of studies, ethical and animal welfare issues, and statistical evaluation. PMID- 22294167 TI - Head-out plethysmography in safety pharmacology assessment. AB - The importance of the ability to accurately evaluate respiratory function in animals has been underscored by the classification of the respiratory system as a vital organ system by regulatory agencies in the United States, the European Union, and Japan. A comprehensive assessment of respiratory function should include an evaluation of ventilatory function, including rate and volume measurements, overall pulmonary ventilation (i.e., minute volume), and lung function, including resistance to lung airflow. A volume-displacement, head-out, plethysmograph chamber is widely considered the most accurate method for measuring respiratory flows and volumes in small animals because it allows direct assessment of both volume and rate as well as resistance to lung airflow, a predictor of airway constriction or obstruction. Direct assessment of airway resistance is important because mild to moderate increases are generally not detected as changes in ventilatory patterns. This unit describes a method for evaluating ventilatory and lung function in conscious rats. PMID- 22294168 TI - Toxicology in the drug discovery and development process. AB - The primary objective of toxicology studies in the drug development process is to evaluate the safety of potential drug candidates. This is accomplished using relevant animal models and validated procedures. The ultimate goal is to translate the animal model responses into an understanding of the risk for human subjects. To this end, the toxicologist must be aware of the international guidelines for safety evaluation, as well as traditional and nontraditional toxicology models. As described in this unit, the typical toxicology profile consists of safety pharmacology, genetic toxicology, acute and subchronic toxicology, chronic toxicology, absorption, distribution, metabolism, and excretion (ADME) studies, reproductive and developmental toxicology, and an evaluation of carcinogenic potential. PMID- 22294169 TI - An overview of QT interval assessment in safety pharmacology. AB - Medicinal products that prolong cardiac repolarization unintentionally, as assessed in terms of prolongation of the QT interval of the electrocardiogram, may trigger a potentially fatal arrhythmia called torsade de pointe (TDP). This lethal risk necessitates a detailed preclinical evaluation before initiating clinical trials. There are two different and complementary approaches to assess the potential of drugs to cause QT interval prolongation. The in vivo approach provides information on the potential of the compound to prolong the QT interval under near-physiological conditions. It is mostly descriptive and not explanatory in terms of mechanisms of action. The in vitro approach provides much more mechanistic information, but is far removed from the clinical situation. While both approaches appear to possess reasonable predictive value, the results may depend largely on the experimental conditions employed. This unit reviews these issues and discusses a strategy aimed at understanding the problems associated with this cardiovascular risk. PMID- 22294170 TI - The action potential of the Purkinje fiber: an in vitro model for evaluation of the proarrhythmic potential of cardiac and noncardiac drugs. AB - The proarrhythmic potential of new chemical entities can be investigated using in vitro electrophysiological techniques measuring the cardiac action potential in isolated Purkinje fibers. Different types of arrhythmias may occur as early afterdepolarizations (EADs), which are favored by action potential duration lengthening and bradycardia, or as delayed afterdepolarizations (DADs), which are facilitated by tachycardia. The effects of a test compound on the occurrence of these arrhythmias, thought to be responsible for the development of torsades de pointes in the clinic can be studied using the experimental protocols described in this unit. PMID- 22294171 TI - Detection of nitros(yl)ated metabolites of nitric oxide (NO) in vivo by gas-phase chemiluminescence assay. AB - There are several methods utilized for detection of nitric oxide (NO) and its various metabolites in biological systems. These include spectrophotometric analysis, high performance liquid chromatography, mass spectrophotometry, electro paramagnetic resonance (EPR), and gas-phase chemiluminscence. Of these, the gas phase chemiluminescence technique is perhaps the most sensitive, with a limit of detection in the femtomole range. Furthermore, as there are a number of commercially available NO analyzers, it is possible to directly compare results from different laboratories using this technique. Described in this unit is a group-specific derivatization approach with gas-phase chemiluminscence detection to profile NO metabolites in vivo. PMID- 22294172 TI - Preparation of nuclear and cytoplasmic extracts from mammalian cells. AB - Extracts prepared from the isolated nuclei of cultured cells have been instrumental in dissecting the mechanisms by which transcription and mRNA processing occur. These extracts are able to recapitulate accurate transcription initiation and splicing in vitro, which has been useful in direct functional studies. They also serve as the starting material for purification of proteins that can then be reassembled in functional studies or examined in more detail biochemically. This unit describes the preparation of nuclear extracts from cultured cells and optimized production of transcriptionally active extracts from HeLa cells. Additional protocols describe optimization of the method to increase the yield of specific proteins, adaptation of the method for downstream applications such as affinity purification, and preparation of the cytoplasmic (S 100) fraction. PMID- 22294173 TI - In vivo animal models: quantitative models used for identifying antibacterial agents. AB - Determining the in vivo bactericidal potential of novel agents is critical for selecting drug candidates. Described in this unit are two protocols that measure the amount of bacterial killing under very different conditions. The mouse pouch protocol is a rapid assay that provides efficacy data in an acute infection, whereas the rabbit tissue cage protocol assesses the ability of a compound to eradicate bacteria in a chronic abscess infection. Data from these tests, along with those from other qualitative and quantitative assays, are important for defining antibacterial efficacy in vivo. PMID- 22294174 TI - In vitro antibacterial resistance selection and quantitation. AB - The study of resistance is vital to the discovery and development of new antibacterial agents. Consider the case where the resistance frequency (the proportion of cells within a population that exhibit a resistance phenotype to the agent under study) of an agent is such that, in an average infection, a mutant resistant to the agent is likely to already exist. This compound will not be useful in the clinic as a single agent, since this mutant can survive its administration, leading to potential clinical failure. This unit provides protocols for determining the frequency and rate of resistance to antibacterial agents, as well as generating resistant mutants for mechanism of action determinations or for use in antibacterial discovery or development programs. PMID- 22294175 TI - Dog EEG for wake-promotion studies. AB - Described in this unit is a protocol for investigating the wake-promoting activity of new chemical entities (NCEs) in dog. The experimental approach is based on scoring of sleep/wake stages in animals implanted with a telemetry device for recording EMG and cortical EEG signals. A major advantage of this procedure is that it is conducted in nontethered animals, limiting possible bias and complications encountered with conventional recording systems. In this procedure, polygraphic recording is conducted using four implanted beagles. Results of studies with modafinil, a wake-promoting agent, are described to demonstrate the utility of this test procedure. PMID- 22294176 TI - Rat model for evaluation of therapeutics on peripheral vascular resistance. AB - Described in this protocol is a rat preparation that serves as a sensitive, reliable in vivo assay of peripheral vascular resistance. Experiments are conducted on conscious animals 5 days following the surgical implantation of an arterial pressure catheter in the carotid artery and a transit time flow probe on the abdominal aorta. The transit time flow probe measures volume blood flow per unit time, making it possible to calculate a true vascular resistance, a reliable indicator of microvascular tone. After allowing appropriate recovery time between experiments, it is possible to use the animal preparation multiple times. This increases study efficiency by reducing the number of animals required and makes it possible to use paired statistical analysis since multiple treatment interventions, including control conditions, can be evaluated in each animal. PMID- 22294177 TI - In vitro species comparisons and metabolite identification. AB - The metabolism and elimination of a drug has a direct bearing on its potential to cause toxicity in humans as well as to influence its clinical activity. The confidence with which data from preclinical safety studies, particularly toxicology studies, can be extrapolated to humans depends upon knowing whether humans are exposed to the same chemical entities (i.e., a parent drug and its metabolites) as the laboratory animals used to study toxicity and pharmacological responses. To address this issue, the FDA Guidance for Industry (1997) recommends the use of in vitro interspecies metabolic comparisons at an early stage in the drug development process. Knowledge about the metabolism of a compound is also important from a drug discovery perspective. In vitro studies provide a convenient and cost-effective way to obtain this information. This unit presents protocols for comparing metabolite profiles across several species, as well as methods for identifying metabolites. PMID- 22294178 TI - Determination of compound binding to plasma proteins. AB - The pharmacokinetic and pharmacodynamic properties of a compound are profoundly affected by the extent of its binding to plasma proteins. Consequently, the determination of the plasma protein binding properties of a compound is essential during drug development and is increasingly required during lead prioritization. The protocols described in this unit detail the techniques of ultrafiltration and equilibrium dialysis for determination of plasma protein binding. Equilibrium dialysis is the more robust of the two techniques, whereas ultrafiltration is the more rapid. Two versions of the equilibrium dialysis technique are provided: the traditional approach and a higher-throughput 96-well plate version. PMID- 22294179 TI - Testing for inverse agonism with constitutive receptor systems. AB - This unit discusses the use of constitutive 7-transmembrane/G protein coupled receptor (7TM/GPCR) activity for screening new drug entities. Following an introduction to constitutive 7TM/GPCR activity, the unit centers on the three basic components of a constitutive screening system: the receptor, the receptor coupling components (G protein), and the response reporting system. The design of specific assays to detect inverse agonism and the application of such systems to drug screening are also discussed. Finally, the relative advantages and disadvantages of inverse agonists as therapeutic agents are considered. PMID- 22294180 TI - Approaches to the molecular modeling of 7-transmembrane helical receptors. AB - 7-Transmembrane helical receptors (7TMs) represent the single most important class of target for drug therapy; therefore, a great deal of effort has gone into computational studies of their structures. Historically, these were based on low resolution electron diffraction data, together with the use of computational methods such as multiple sequence alignments, distance geometry, and molecular mechanics calculations. In the year 2000 the situation changed when the first crystal structure of a 7TM, was published. It was then possible to use the homology modeling techniques to generate more accurate models of these proteins. This unit reviews the modeling of 7TMs and describes in detail how homology modeling can be used to build a structure of the 5-HT2a receptor. Special attention is given to the initial sequence alignment, the most important step in the process. Use of automatic alignment programs often produces incorrect results, and manual intervention is necessary before proceeding further. PMID- 22294181 TI - Overview of drug discovery and development. AB - This overview unit describes the core activities involved in the drug discovery and development process, from target identification - including preclinical biology, medicinal and process chemistry - to pharmacokinetics and metabolism (ADME), and also activities related to the to the drug approval process. The latter include the activities related to the filing of an IND (Investigational New Drug) application and also Phases I - III of clinical trials that form the basis of an NDA (New Drug Application) submission, as well as post-marketing Phase IV activities as required by the U.S. Food and Drug Administration (FDA) and the European and Japanese counterparts. PMID- 22294182 TI - Pre-treatment plasma proteomic markers associated with survival in oesophageal cancer. AB - BACKGROUND: The incidence of oesophageal adenocarcinoma is increasing worldwide but survival remains poor. Neoadjuvant chemotherapy can improve survival, but prognostic and predictive biomarkers are required. This study built upon preclinical approaches to identify prognostic plasma proteomic markers in oesophageal cancer. METHODS: Plasma samples collected before and during the treatment of oesophageal cancer and non-cancer controls were analysed by surface enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) mass spectroscopy (MS). Protein peaks were identified by MS in tryptic digests of purified fractions. Associations between peak intensities obtained in the spectra and clinical endpoints (survival, disease-free survival) were tested by univariate (Fisher's exact test) and multivariate analysis (binary logistic regression). RESULTS: Plasma protein peaks were identified that differed significantly (P<0.05, ANOVA) between the oesophageal cancer and control groups at baseline. Three peaks, confirmed as apolipoprotein A-I, serum amyloid A and transthyretin, in baseline (pre-treatment) samples were associated by univariate and multivariate analysis with disease-free survival and overall survival. CONCLUSION: Plasma proteins can be detected prior to treatment for oesophageal cancer that are associated with outcome and merit testing as prognostic and predictive markers of response to guide chemotherapy in oesophageal cancer. PMID- 22294183 TI - Serum 20S proteasome is elevated in patients with renal cell carcinoma and associated with poor prognosis. AB - BACKGROUND: To date, no reliable serum marker for clear cell renal cell carcinoma (CCRCC) is available. The aim of this study was to evaluate the putative significance of circulating 20S proteasome levels. METHODS: Preoperative 20S proteasome serum levels were determined in 113 CCRCC patients and 15 healthy controls by a sandwich enzyme-linked immunosorbent assay. Associations with CCRCC, pathological variables, disease-specific survival (DSS), and response to sunitinib were evaluated. RESULTS: Median 20S proteasome levels were higher in CCRCC patients than in healthy controls (4.66 vs 1.52 MUg ml(-1), P<0.0001). The area under the receiver operating characteristics curve curve was 87.1%. The 20S proteasome levels were associated with symptoms (P=0.0008), distant metastases (P=0.0011), grade (P=0.0247), and necrosis (P=0.0462). The 20S proteasome levels were identified as a prognostic factor for DSS in both univariable (hazards ratio 1.21, P<0.001) and multivariable (hazards ratio 1.17, P=0.0015) survival analysis. In patients responding to sunitinib, 20S proteasome levels were lower than in patients with stable disease and progressive disease. CONCLUSION: This study demonstrates for the first time that increased 20S proteasome levels are associated with CCRCC, advanced disease, and poor prognosis. Routine use of this marker may allow better diagnosis, risk stratification, risk-adjusted follow-up, and identification of patients with a greater likelihood of response to targeted therapy. PMID- 22294184 TI - The association of statins and taxanes: an efficient combination trigger of cancer cell apoptosis. AB - BACKGROUND: Cancer cell killing might be achieved by the combined use of available drugs. Statins are major anti-hypercholesterolemia drugs, which also trigger apoptosis of many cancer cell types, while docetaxel is a potent microtubule-stabilising agent. METHODS: Here, we looked at the combined effects of lovastatin and docetaxel in cancer cells. RESULTS: Whole transcriptome microarrays in HGT-1 gastric cancer cells demonstrated that lovastatin strongly suppressed expression of genes involved in cell division, while docetaxel had very little transcriptional effects. Both drugs triggered apoptosis, and their combination was more than additive. A marked rise in the cell-cycle inhibitor p21, together with reduction of aurora kinases A and B, cyclins B1 and D1 proteins was induced by lovastatin alone or in combination with docetaxel. The drug treatments induced the proteolytic cleavage of procaspase-3, a drop of the anti-apoptotic Mcl-1 protein, Poly-ADP-Ribose Polymerase and Bax. Strikingly, docetaxel-resistant HGT-1 cell derivatives overexpressing the MDR-1 gene were much more sensitive to lovastatin than docetaxel-sensitive cells. CONCLUSION: These results suggest that the association of lovastatin and docetaxel, or lovastatin alone, shows promise as plausible anticancer strategies, either as a direct therapeutic approach or following acquired P-glycoprotein-dependent resistance. PMID- 22294185 TI - Severe toxicity caused by sorafenib in hepatocellular carcinoma match the data from renal cell carcinoma. PMID- 22294186 TI - Supernatants derived from chemotherapy-treated cancer cell lines can modify angiogenesis. AB - BACKGROUND: There is evidence that tumours produce substances such as cytokines and microvesicular bodies bearing bioactive molecules, which support the carcinogenic process. Furthermore, chemotherapy has also been shown to modify these exudates and in doing so, neutralise their tumourigenic influence. METHODS: In the current study, we have investigated the effect of chemotherapy agents on modifying the cytokine profile and microvesicular cargo of supernatants derived from cancer cell lines. In addition, we have explored the effect of these tumour derived supernatants on angiogenesis, and how chemotherapy can alter the supernatants rendering them less pro-angiogenic. RESULTS: Herein, we show that supernatants contain a rich cocktail of cytokines, a number of which are potent modulators of angiogenesis. They also contain microvesicular bodies containing RNA transcripts that code for proteins involved in transcription, immune modulation and angiogenesis. These supernatants altered intracellular signalling molecules in endothelial cells and significantly enhanced their tubulogenic character; however, this was severely compromised when supernatants from tumours treated with chemotherapy was used instead. CONCLUSION: This study suggests tumour exudates and bioactive material from tumours can influence cellular functions, and that treatment with some chemotherapy can serve to negate these pro-tumourigenic processes. PMID- 22294187 TI - Skin cancer screening participation and impact on melanoma incidence in Germany- an observational study on incidence trends in regions with and without population based screening. AB - BACKGROUND: The SCREEN (Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany) project involved population-wide skin cancer screening with whole-body examination by general physicians and dermatologists. It was conducted in the German state of Schleswig-Holstein (July 2003-June 2004), but not in the German state of Saarland. METHODS: The population based registries of Schleswig-Holstein and Saarland provided data on melanoma incidence before, during, and after SCREEN to assess the association of skin cancer screening with incidence. RESULTS: Approximately 19% of the Schleswig Holstein population participated in SCREEN (women: 27%, men: 10%). A total of 52% of all melanomas diagnosed during SCREEN in Schleswig-Holstein were detected as part of the project. Melanoma incidence increased during SCREEN (invasive melanoma in women: +8.9 per 100,000 (95% confidence intervals (CI): 6.1; 11.7); men: +4.0 per 100,000 (95% CI: 1.6; 6.4)) and decreased afterwards (women: -10.6 per 100,000 (95% CI: -13.3; -7.9); men: -4.1 per 100,000 (95% CI: -6.5; -1.7)). Similar changes were not observed in Saarland that had no such project. The differences between the two states were greatest among women, the group with the greater SCREEN participation. CONCLUSION: The SCREEN project had a substantial impact on melanoma incidence. This is consistent with the impact of effective screening for other cancers. PMID- 22294188 TI - Clinical significance of CD151 overexpression in subtypes of invasive breast cancer. AB - BACKGROUND: CD151 is a member of the tetraspanin family, which interacts with laminin-binding integrins and other tetraspanins. This protein is implicated in motility, invasion, and metastasis of cancer cells, but the prevalence of CD151 expression in subtypes of breast cancers and its influence on clinical outcome remains to be evaluated. METHODS AND RESULTS: The immunohistochemistry-based tissue microarray analysis showed that 127 (14.3%) cases overexpressed CD151 among 886 breast cancer patients. CD151 overexpression was found to be significantly associated with larger tumour size, higher nodal stage, advanced stage, absence of oestrogen receptor and progesterone receptor, and human epidermal growth factor receptor 2 overexpression. CD151 overexpression resulted in poorer overall survival (OS) (P<0.001) and disease-free survival (P=0.02), and stage II and III patients with CD151 overexpression demonstrated substantially poorer OS (P=0.0474 and 0.0169). In the five subtypes analyses, CD151 overexpression retained its adverse impact on OS in the Luminal A (P=0.0105) and quintuple-negative breast cancer (QNBC) subtypes, one subgroup of triple-negative breast cancer (P=0.0170). Multivariate analysis that included stage, subtype, and adjuvant chemotherapy showed that CD151 overexpression was independently associated with poor OS in invasive breast cancer. CONCLUSION: CD151 overexpression may be a potential molecular therapeutic target for breast cancer, especially in QNBC subtype and more advanced stages of breast cancer. PMID- 22294189 TI - Spontaneous nephrocolic fistula secondary to a staghorn calculus. PMID- 22294190 TI - Appropriate interval between endometrial polyp resection and the proceeding IVF start. AB - PURPOSE: Endometrial polyp is the commenest pathology among the structural uterine abnormalities. In this study we compared the IVF outcomes of patients who underwent hysteroscopic endometrial polyp excision with respect to the time interval between the polyp resection and the subsequent IVF cycle. MATERIALS AND METHODS: A total of 60 patients were divided into two groups according to the time interval between the hysteroscopic polyp resection and the start of the following IVF cycle. Of these, 29 patients had the IVF procedures <6 months after the polyp resection, whereas in 31 patients comprising the comparison group, IVF interventions were done >= 6 months after the resection. The IVF outcomes were compared. RESULTS: Differences in the mean number of retrieved oocytes, metaphase II (MII) oocytes and transferred embryos, ratios of MII oocytes, and G1, G2 and G3 embryo rates were insignificant between the groups (p > 0.05). The fertilization, implantation, and clinical pregnancy rates were also similar between the groups (p > 0.05). CONCLUSION: IVF outcomes seem to be unrelated to the time interval between the hysteroscopic polyp resection and the initiation of the IVF; the success rates may not be superior if the treatment is started in the first few months postoperatively. PMID- 22294191 TI - Effect of inhibition of the adrenomedullin gene on the growth and chemosensitivity of ovarian cancer cells. AB - Adrenomedullin (AM), a potent vasodilator peptide, is present in various types of tumors. Here, we constructed short hairpin RNA (shRNA) in order to target the AM gene in vitro using RNA interference (RNAi) technology. HO8910 ovarian cancer cells were transfected, and the effects of AM on proliferation and chemosensitivity of the cells were examined. RT-PCR, real-time PCR and western blot analysis were performed to detect the AM gene and protein expression. The MTT assay was used to observe the effect of AM on proliferation and chemosensitivity of the cells. Also, the protein levels of bcl-2 and the extracellular regulated protein kinase (ERK) were evaluated by western blot analysis. We found that silencing of the AM gene inhibited the proliferation and increased the chemosensitivity of HO8910 cells, reduced the expression of AM mRNA and protein as well as downregulated bcl-2 and p-ERK expression. We, therefore, conclude that silencing of the AM gene in HO8910 ovarian cancer cells inhibited the proliferation and increased the chemosensitivity of the cells through downregulation of ERK and bcl-2 expression. Thus, anti-AM treatment together with suppression of ERK and bcl-2 expression provides a novel research approach for ovarian cancer. PMID- 22294192 TI - Extended lymphadenectomy does not improve prognosis in pancreatic carcinoma: is that really so? PMID- 22294194 TI - A multicenter validation of an endoscopic classification with narrow band imaging for gastric precancerous and cancerous lesions. AB - BACKGROUND AND STUDY AIM: The reliability and external validity of narrow band imaging (NBI) in the stomach have not been described consistently. The aim of the current study was to describe and estimate the accuracy and reliability of a simplified classification system for NBI in the diagnosis of gastric lesions. METHODS: Consecutive patients undergoing NBI endoscopy at two reference centers (n=85, 33% with dysplasia) were included in two studies. In total, 224 different areas were biopsied and recorded onto video. In the derivation study, previously described NBI features were analyzed in order to develop a simplified classification. In the validation study the accuracy and reliability of this classification were estimated among three groups of endoscopists with different levels of expertise in NBI. RESULTS: The reliability/accuracy results from the derivation study allowed the creation of a simplified NBI classification. In the validation study, "regular vessels with circular mucosa" (pattern A) was associated with normal histology (accuracy 83%; 95% confidence interval [CI] 75 % 90%); "tubulo-villous mucosa" (pattern B) was associated with intestinal metaplasia (accuracy 84%; 95CI 77%-91%; positive likelihood ratio [LR+]=4.75); and "irregular vessels and mucosa" (pattern C) was associated with dysplasia (accuracy 95%; 95CI 90%-99%; LR+=44.33). The reproducibility of these patterns was high (k=0.62). "Light-blue crest" was moderately reliable (k=0.49) but specific (87%) for intestinal metaplasia. A variable vascular density (additional pattern+) was the best feature for Helicobacter pylori gastritis (accuracy 70%; 95CI 59%-80%) but showed only fair reliability (k=0.38). Non-experienced endoscopists presented lower agreement (k=0.6 vs. k=0.75) and accuracy (74% vs. 86%) than international experts/experienced endoscopists. CONCLUSION: A simplified NBI classification is accurate and reliable for the diagnosis of intestinal metaplasia and dysplasia. The classification should be further assessed and validated on a per-patient assessment of NBI, and by comparing NBI with other imaging technologies. PMID- 22294195 TI - Methotrexate reduces the occurrence of cerebrovascular events among Taiwanese psoriatic patients: a nationwide population-based study. AB - Psoriasis is a chronic inflammatory disease. The aim of this study was to evaluate the effects of methotrexate and retinoid on risks for developing cerebrovascular disease among psoriatic patients. A population-based nested case control study was conducted using the Taiwanese National Health Insurance database. Cox proportional hazards models were adopted. The hazard ratio (HR) of newly developed cerebrovascular disease was 1.28 (95% confidence interval (CI) = 1.162-1.413; p < 0.0001) for psoriatic vs. non-psoriatic subjects. In terms of the effects of methotrexate or retinoid on the occurrence of cerebrovascular disease, a significant protection effect (HR = 0.50; 95% CI = 0.27-0.92; p = 0.0264) was found for patients with methotrexate prescription. Retinoid prescription showed no protective effect. Further analyses revealed that a low cumulative methotrexate dose is associated with significant protective effect (HR = 0.53; 95% CI = 0.28-1.00; p = 0.0486) while a high cumulative dose was not (HR 0.80; 95% CI = 0.11-5.68; p = 0.8214). These results suggest that psoriatic patients receiving low-dose methotrexate treatment may have reduced risk for developing cerebrovascular disease. Further prospective study should be performed to validate the vasculoprotective effect of this treatment strategy. PMID- 22294196 TI - Mutation spectrum of the TYR and SLC45A2 genes in patients with oculocutaneous albinism. AB - Oculocutaneous albinism (OCA) is a group of inherited disorders characterized by defective melanin biosynthesis. OCA1, the most common and severe form, is caused by mutations in the tyrosinase (TYR) gene. OCA4, caused by mutations in the SLC45A2 gene, has frequently been reported in the Japanese population. To determine the mutational spectrum in Korean OCA patients, 12 patients were recruited. The samples were first screened for TYR mutations, and negative samples were screened for SLC45A2 mutations. OCA1 was confirmed in 8 of 12 (66.7%) patients, and OCA4 was diagnosed in 1 (8.3%) patient. In the OCA1 patients, a total of 6 distinct TYR mutations were found in 15 of 16 (93.8%) alleles, all of which had been previously reported. Out of the 6 alleles, c.929insC was the most frequently detected (31.3%), and was mainly associated with OCA1A phenotypes. Other TYR mutations identified included c.1037-7T>A/c.1037 10delTT, p.D383N, p.R77Q and p.R299H. These largely overlapped with mutations found in Japanese and Chinese patients. The SLC45A2 gene analysis identified 1 novel mutation, p.D93N, in 1 patient. This study has provided information on the mutation spectrum in Korean OCA patients, and allows us to estimate the relative frequencies of OCA1 and OCA4 in Korea. PMID- 22294197 TI - Efficient synthesis of isochromanones and isoquinolines via Yb(OTf)3-catalyzed tandem oxirane/aziridine ring opening/Friedel-Crafts cyclization. AB - The first example of Yb(OTf)(3)-catalyzed tandem ring opening/Friedel-Crafts cyclization of oxiranyl and aziridinyl ketones via selective C-C bond cleavage under mild conditions was developed. Isochromanones and isoquinolines are formed in reasonable yields, which often serve as building blocks for complex chemical synthesis. PMID- 22294198 TI - Adaptive radiotherapy for soft tissue changes during helical tomotherapy for head and neck cancer. AB - PURPOSE: The goal of the present study was to assess the frequency and impact of replanning triggered solely by soft tissue changes observed on the daily setup mega-voltage CT (MVCT) in head and neck cancer (H&N) helical tomotherapy (HT). MATERIAL AND METHODS: A total of 11 patients underwent adaptive radiotherapy (ART) using MVCT. Preconditions were a soft tissue change > 0.5 cm and a tight mask. The dose-volume histograms (DVHs) derived from the initial planning kVCT (inPlan), the recalculated DVHs of the fraction (fx) when replanning was decided (actSit) and the DVHs of the new plan (adaptPlan) were compared. Assessed were the following: maximum dose (Dmax), minimum dose (Dmin), and mean dose (Dmean) to the planning target volume (PTV) normalized to the prescribed dose; the Dmean/fx to the parotid glands (PG), oral cavity (OC), and larynx (Lx); and the Dmax/fx to the spinal cord (SC) in Gy/fx. RESULTS: No patient had palpable soft tissue changes. The median weight loss at the moment of replanning was 2.3 kg. The median PTV Dmean was 100% for inPlan, 103% for actSit, and 100% for adaptPlan. The PTV was always covered by the prescribed dose. A statistically significant increase was noted for all organs at risk (OAR) in the actSit. The Dmean to the Lx, the Dmean to the OC and the Dmax to the SC were statistically better in the adaptPlan. No statistically significant improvement was achieved by ART for the PGs. No significant correlations between weight and volume loss or between the volume changes of the organs to each other were observed, except a strong positive correlation of the shrinkage of the PGs (rho = + 0.77, p = 0.005). CONCLUSION: Soft tissue shrinkage without clinical palpable changes will not affect the coverage of the PTV, but translates into a higher delivered dose to the PTV itself and the normal tissue outside the PTV. The gain by ART in individual patients-especially in patients who receive doses close to the tolerance doses of the OAR-could be substantial. PMID- 22294200 TI - On the fluorescence of methyl salicylate: the significance of its IMHB. AB - The two forms of methyl salicylate bearing an intramolecular hydrogen bond (IMHB) are responsible for the three fluorescence emissions produced by this compound on electronic excitation in inert media. Whereas the form possessing an IMHB between its hydroxyl group and ether oxygen undergoes no excited state intramolecular proton transfer (ESIPT) in its first excited electronic state, that with an IMHB involving the carbonyl oxygen exhibits ESIPT with near-unity efficiency. Whereas the former species exhibits standard photophysical behaviour, the latter species exhibits two fluorescence emissions from the same electronic excited state; a photophysical scheme is proposed, which brings together all the available photophysical evidence for methyl salicylate in inert media. PMID- 22294201 TI - Psoriatic arthritis: a critical review. AB - Psoriatic arthritis is a chronic inflammatory arthritis that affects about 5-25% of patients with psoriasis. The prevalence varies from 20-420 per 100,000 population across the world except in Japan where it is 1 per 100,000. Psoriatic arthritis affects both genders equally and in more than half it follows long standing psoriasis. Psoriatic arthritis has been grouped into five subtypes: distal interphalangeal (DIP) predominant, symmetrical polyarthritis, asymmetrical oligoarthritis and monoarthritis, predominant spondylitis, and arthritis mutilans. Oligoarthritis occurs in nearly 60% during early disease but later polyarticular disease predominates mainly due to evolution of oligoarthritis to polyarthritis. In 50-60% polyarthritis is symmetrical. Dactylitis and enthesopathy are other major features seen in nearly one third of patients. The diagnosis of psoriatic arthritis is easy in the presence of typical skin lesions, however it can also be made in absence of skin lesions using Classification of Psoriatic Arthritis criteria. Though 30-40% of patients develop joint deformities at a follow-up of 5-10 years but most retain good functional status. Clinical damage has a strong relationship with number of swollen joints, erythrocyte sedimentation rate, and duration of arthritis. Radiological damage occurs early and erosions are present in nearly 50% at 10 years of disease. Spinal disease also has good outcome with maintained spinal mobility in majority of the patients. Screening of patients with psoriasis using questionnaire can help in early diagnosis. Nail dystrophy, scalp lesions, and intergluteal/perianal psoriasis are associated with higher chance of development of psoriatic arthritis. Early diagnosis will lead to early treatment and better outcome especially with advent of new drugs. PMID- 22294202 TI - Imaging in psoriatic arthritis. AB - Psoriatic arthritis (PsA), a chronic inflammatory arthritis associated with psoriasis, is often associated with significant inflammation and joint damage leading to a decrease in quality of life measures. Plain radiographs have traditionally been used to detect and estimate the extent of joint damage. Newer imaging modalities such as ultrasound and MRI however, have provided the ability to detect joint damage earlier and measure the extent of joint damage more accurately, than with radiographs. These imaging modalities also provide a sensitive means of assessing for the presence of and quantifying the amount of inflammation. Furthermore, these imaging modalities can help with the identification of enthesitis, tendonitis, and dactylitis, features that can help make a diagnosis of PsA. Additionally, MRI and scintigraphy can help in the early detection and assessment of sacroiliitis and axial disease. In addition to benefits with diagnosis and prognosis, recent advances in imaging techniques have led to their increased use in the assessment of efficacy of novel therapies for psoriatic arthritis. Imaging modalities therefore allow for early detection, assessment of joint inflammation and joint damage as well as in the estimation of disease activity of PsA and thereby enable the clinician to treat PsA early, adequately, and safely. PMID- 22294203 TI - Q&A: Reasons for proposed redaction of flu paper. PMID- 22294204 TI - Policy: Adaptations of avian flu virus are a cause for concern. PMID- 22294205 TI - Microglial stimulation of glioblastoma invasion involves epidermal growth factor receptor (EGFR) and colony stimulating factor 1 receptor (CSF-1R) signaling. AB - Glioblastoma multiforme is a deadly cancer for which current treatment options are limited. The ability of glioblastoma tumor cells to infiltrate the surrounding brain parenchyma critically limits the effectiveness of current treatments. We investigated how microglia, the resident macrophages of the brain, stimulate glioblastoma cell invasion. We first examined the ability of normal microglia from C57Bl/6J mice to stimulate GL261 glioblastoma cell invasion in vitro. We found that microglia stimulate the invasion of GL261 glioblastoma cells by approximately eightfold in an in vitro invasion assay. Pharmacological inhibition of epidermal growth factor receptor (EGFR) strongly inhibited microglia-stimulated invasion. Furthermore, blockade of colony stimulating factor 1 receptor (CSF-1R) signaling using ribonucleic acid (RNA) interference or pharmacological inhibitors completely inhibited microglial enhancement of glioblastoma invasion. GL261 cells were found to constitutively secrete CSF-1, the levels of which were unaffected by epidermal growth factor (EGF) stimulation, EGFR inhibition or coculture with microglia. CSF-1 only stimulated microglia invasion, whereas EGF only stimulated glioblastoma cell migration, demonstrating a synergistic interaction between these two cell types. Finally, using PLX3397 (a CSF-1R inhibitor that can cross the blood-brain barrier) in live animals, we discovered that blockade of CSF-1R signaling in vivo reduced the number of tumor associated microglia and glioblastoma invasion. These data indicate that glioblastoma and microglia interactions mediated by EGF and CSF-1 can enhance glioblastoma invasion and demonstrate the possibility of inhibiting glioblastoma invasion by targeting glioblastoma-associated microglia via inhibition of the CSF 1R. PMID- 22294206 TI - Highly efficient catalysts for Co(II/III) redox couples in dye-sensitized solar cells. AB - We developed several low-cost catalysts with high catalytic activity, which were used as counter electrodes in dye-sensitized solar cells (DSCs). They showed higher efficiencies than that of Pt. The efficiencies were improved by 18-42% for the DSCs composed of active carbon, niobium dioxide, ordered mesoporous carbon and commercial titanium carbide. PMID- 22294207 TI - Voltage-dependent-anion-channels (VDACs) in Arabidopsis have a dual localization in the cell but show a distinct role in mitochondria. AB - In mammals, the Voltage-dependent anion channels (VDACs) are predominant proteins of the outer mitochondrial membrane (OMM) where they contribute to the exchange of small metabolites essential for respiration. They were shown to be as well associated with the plasma membrane (PM) and act as redox enzyme or are involved in ATP release for example. In Arabidopsis, we show that four out of six genomic sequences encode AtVDAC proteins. All four AtVDACs are ubiquitously expressed in the plant but each of them displays a specific expression pattern in root cell types. Using two complementary approaches, we demonstrate conclusively that the four expressed AtVDACs are targeted to both mitochondria and plasma membrane but in differential abundance, AtVDAC3 being the most abundant in PM, and conversely, AtVDAC4 almost exclusively associated with mitochondria. These are the first plant proteins to be shown to reside in both these two membranes. To investigate a putative function of AtVDACs, we analyzed T-DNA insertion lines in each of the corresponding genes. Knock-out mutants for AtVDAC1, AtVDAC2 and AtVDAC4 present slow growth, reduced fertility and yellow spots in leaves when atvdac3 does not show any visible difference compared to wildtype plants. Analyses of atvdac1 and atvdac4 reveal that yellow areas correspond to necrosis and the mitochondria are swollen in these two mutants. All these results suggest that, in spite of a localization in plasma membrane for three of them, AtVDAC1, AtVDAC2 and AtVDAC4 have a main function in mitochondria. PMID- 22294208 TI - Computational assessment of bicuspid aortic valve wall-shear stress: implications for calcific aortic valve disease. AB - The bicuspid aortic valve (BAV) is associated with a high prevalence of calcific aortic valve disease (CAVD). Although abnormal hemodynamics has been proposed as a potential pathogenic contributor, the native BAV hemodynamic stresses remain largely unknown. Fluid-structure interaction models were designed to quantify the regional BAV leaflet wall-shear stress over the course of CAVD. Systolic flow and leaflet dynamics were computed in two-dimensional tricuspid aortic valve (TAV) and type-1 BAV geometries with different degree of asymmetry (10 and 16% eccentricity) using an arbitrary Lagrangian-Eulerian approach. Valvular performance and regional leaflet wallshear stress were quantified in terms of valve effective orifice area (EOA), oscillatory shear index (OSI) and temporal shear magnitude (TSM). The dependence of those characteristics on the degree of leaflet calcification was also investigated. The models predicted an average reduction of 49% in BAV peak-systolic EOA relative to the TAV. Regardless of the anatomy, the leaflet wall-shear stress was side-specific and characterized by high magnitude and pulsatility on the ventricularis and low magnitude and oscillations on the fibrosa. While the TAV and non-coronary BAV leaflets shared similar shear stress characteristics, the base of the fused BAV leaflet fibrosa exhibited strong abnormalities, which were modulated by the degree of calcification (6-fold, 10-fold and 16-fold TSM increase in the normal, mildly and severely calcified BAV, respectively, relative to the normal TAV). This study reveals the existence of major differences in wall-shear stress pulsatility and magnitude on TAV and BAV leaflets. Given the ability of abnormal fluid shear stress to trigger valvular inflammation, the results support the existence of a mechano-etiology of CAVD in the BAV. PMID- 22294209 TI - Synthesis and characterizations of quaternary Cu2FeSnS4 nanocrystals. AB - Quaternary tetragonal Cu(2)FeSnS(4) nanocrystals have been synthesized by a simple hot-injection method. Detailed characterizations have been made. A suitable optical band gap of 1.28 +/- 0.02 eV and a notable and stable photoelectrochemical response indicate their potential for application in solar cells. PMID- 22294210 TI - The surface termination effect on the quantum confinement and electron affinities of 3C-SiC quantum dots: a first-principles study. AB - In light of the established differences between the quantum confinement effect and the electron affinities between hydrogen-passivated C and Si quantum dots, we carried out theoretical investigations on SiC quantum dots, with surfaces uniformly terminated by C-H or Si-H bonds, to explore the role of surface terminations on these two aspects. Surprisingly, it was found that the quantum confinement effect is present (or absent) in the highest occupied (or lowest unoccupied) molecular orbital of the SiC quantum dots regardless of their surface terminations. Thus, the quantum confinement effect related to the energy gap observed experimentally (Phys. Rev. Lett., 2005, 94, 026102) is contributed to by the size-dependence of the highest occupied states; the absence of quantum confinement in the lowest unoccupied states is in contrary to the usual belief based on hydrogen-passivated C quantum dots. However, the cause of the absence of the quantum confinement in C nanodots is not transferable to SiC. We propose a model that provides a clear explanation for all findings on the basis of the nearest-neighbor and next-nearest-neighbor interactions between the valence atomic p-orbital in the frontier occupied/unoccupied states. We also found that the electron affinities of the SiC quantum dots, which closely depend on the surface environments, are negative for the C-H termination and positive for the Si-H termination. The prediction of negative electron affinities in SiC quantum dots by simple C-H termination indicates a promising application for these materials in electron-emitter devices. Our model predicts that GeC quantum dots with hydrogen passivation exhibit similar features to SiC quantum dots and our study confirms the crucial role that the surface environment plays in these nanoscale systems. PMID- 22294211 TI - Prevalence and spectrum diseases predisposing to sudden cardiac death: are they the same for both the athlete and the nonathlete? AB - Sudden cardiac death (SCD) is a rare but devastating event among young people. The precise scale of the event remains undefined. This uncommon but catastrophic event usually is proved to be the consequence of varied unsuspected congenital or acquired cardiovascular diseases. Hypertrophic cardiomyopathy and coronary artery anomalies are the two most frequent causes of SCD. Most commonly, SCD resulting from these diseases occurs during or immediately after exercise. This report highlights the prevalence and spectrum of SCD-predisposing diseases and how they are affected by athletic participation. In addition, disease-specific guidelines for sports participation are addressed. PMID- 22294212 TI - Pulmonary vein atresia with severe contralateral pulmonary vein stenosis in a child. AB - Unilateral pulmonary vein atresia is a very rare congenital anomaly associated with high morbidity and mortality. Most cases present in infancy or childhood with recurrent respiratory infections or hemoptysis. Further, the diagnosis can often be difficult to make. We present an infant who died due to unilateral right sided pulmonary vein atresia in conjunction with severe contralateral pulmonary vein stenosis who was diagnosed with the assistance of cardiac computed tomography scanning. PMID- 22294213 TI - Pattern of cancer/testis antigen expression in lung cancer patients. AB - Cancer/testis (CT) antigens represent promising targets for immunotherapy. We investigated the composite expression of 13 CT antigens by RT-PCR in 79 lung cancer tissues and by immunohistochemistry in 22 lung cancer tissues. In the 79 lung cancer tissues, MAGE-3 (42%) was expressed most frequently and followed by NY-SAR-35 (33%), NY-ESO-1 (30%), MAGE-1 (27%), CT-7 (20%), MAGE-4 (19%), LAGE-1 (16%), and MAGE-10 (14%). Twenty-one tissues did not express any of the CT antigens tested, 58 (73%) expressed at least one, 36 (46%) co-expressed two, 24 (30%) co-expressed three, 17 (22%) co-expressed four, 14 (18%) co-expressed five, 8 (10%) co-expressed six, 4 (6%) co-expressed seven and 2 tissues expressed 9 of the 13 examined CT antigens. Expression of CT antigens was significantly associated with age (P<0.001), smoking history (P=0.009), and gender (P=0.001) of patients, whereas no correlation was found between the expression of CT antigens and other clinical factors, such as pT status, pN status, tumor stage, and histology history. The present results show that CT antigens are potential candidates in lung cancer patients for polyvalent immunotherapy. PMID- 22294214 TI - Interactive Motion Planning for Steerable Needles in 3D Environments with Obstacles. AB - Bevel-tip steerable needles for minimally invasive medical procedures can be used to reach clinical targets that are behind sensitive or impenetrable areas and are inaccessible to straight, rigid needles. We present a fast algorithm that can compute motion plans for steerable needles to reach targets in complex, 3D environments with obstacles at interactive rates. The fast computation makes this method suitable for online control of the steerable needle based on 3D imaging feedback and allows physicians to interactively edit the planning environment in real-time by adding obstacle definitions as they are discovered or become relevant. We achieve this fast performance by using a Rapidly Exploring Random Tree (RRT) combined with a reachability-guided sampling heuristic to alleviate the sensitivity of the RRT planner to the choice of the distance metric. We also relax the constraint of constant-curvature needle trajectories by relying on duty cycling to realize bounded-curvature needle trajectories. These characteristics enable us to achieve orders of magnitude speed-up compared to previous approaches; we compute steerable needle motion plans in under 1 second for challenging environments containing complex, polyhedral obstacles and narrow passages. PMID- 22294215 TI - Assessment of dual tasking has no clinical value for fall prediction in Parkinson's disease. AB - The objective of this study is to investigate the value of dual-task performance for the prediction of falls inpatients with Parkinson's disease (PD). Two hundred sixty three patients with PD (H&Y 1-3, 65.2 +/- 7.9 years)walked two times along a 10-m trajectory, both under single-task and dual-task (DT) conditions (combined with an auditory Stroop task). To control for a cueing effect, Stroop stimuli were presented at variable or fixed 1- or 2-s intervals. The auditory Stroop task was also performed alone. Dual-task costs were calculated for gait speed, stride length, stride time, stride time variability, step and stride regularity, step symmetry and Stroop composite scores(accuracy/reaction time). Subsequently, falls were registered prospectively for 1 year (monthly assessments). Patients were categorized as non-recurrent fallers (no or 1 fall) or recurrent fallers ([1 falls). Recurrent fallers (35%) had a significantly higher disease severity, lower MMSE scores, and higher Timed ''Up & Go'' test scores than non recurrent fallers. Under DT conditions, gait speed and stride lengths were significantly decreased. Stride time, stride time variability, step and stride regularity, and step symmetry did not change under DT conditions. Stroop dual-task costs were only significant for the 2-s Stroop interval trials. Importantly, recurrent fallers did not show different dual-task costs compared to non-recurrent fallers on any of the gait or Stroop parameters. These results did not change after correction for baseline group differences. Deterioration of gait or Stroop performance under dual task conditions was not associated with prospective falls in this large sample of patients with PD. PMID- 22294216 TI - Receptor theory. AB - Receptor theory assigns mathematical rules to biological systems in order to quantify drug effects and define what biological systems can and cannot do, leading to the design of experiments that may further modify the model. Drug receptor theory also furnishes the tools for quantifying the activity of drugs in a system-independent manner, essential because drugs are almost always studied in test systems somewhat removed from the therapeutic system for which they are intended. Since biological systems operate at different set points in the body under different conditions, the ability to predict drug effects under a variety of circumstances is important. This unit provides a historical perspective of classical receptor theory and the currently used operational model of drug effects. The mechanism of drug receptor function is also described in terms of the various iterations of the ternary complex model, the two-state theory for ion channels, and a probabilistic model of multiple receptor conformations. PMID- 22294217 TI - Radioligand binding characterization of neuronal nicotinic acetylcholine receptors. AB - Described in this unit are radioligand binding protocols for three neuronal nicotinic acetylcholine receptor (nAChR) subtypes. Detailed descriptions of binding protocols are presented for the two predominant CNS subtypes of nAChRs, alpha4beta2 and alpha7, as well as the ganglionic alpha3beta4 nAChR. [(3)H]Cytisine is utilized for alpha4beta2 nAChRs, while [(3)H]methyllycaconitine is utilized for alpha7 nAChRs, both in rat brain. alpha3beta4 nAChRs in IMR-32 cells are labeled with [(3)H]epibatidine. Reference data are presented, as well as commentary on the current state of neuronal nicotinic receptor research. PMID- 22294218 TI - Drug testing in cellular chemotaxis assays. AB - Described in this unit are methods for measuring the cell migration process. While cell adhesion protocols allow study of migrating cell interactions with the endothelial matrix, cellular migration assays permit analysis of directed cell movement towards a chemotactic gradient, both in vivo and in vitro. An in vitro cell invasion protocol is provided for analysis of the sum of the cell adhesion, migration, and invasion activities involved in tumor cell motility. PMID- 22294219 TI - In vitro assay of angiogenesis: inhibition of capillary tube formation. AB - The growth of new blood vessels, or angiogenesis, is a naturally occurring process in both health and disease states. An area of active research, regulation of angiogenesis, is being studied as an approach for the treatment of cancer and a range of other disorders having vascular proliferation as a component. The process of angiogenesis is very complex and occurs in multiple steps, with a major involvement of endothelial cells. Various in vivo models have been developed to assess inhibitors of angiogenesis. As these are generally technically difficult and labor intensive, with observed effects difficult to quantify, they do not lend themselves to compound screening. Rather they are used for confirmatory studies. In contrast, in vitro assays developed to model various steps in the angiogenesis process are easy to perform and lend themselves to high throughput analysis. Described in this unit is an in vitro assay that can be employed to investigate endothelial differentiation inhibitors through assessment of their effects on capillary tube formation by endothelial cells on Matrigel. PMID- 22294220 TI - Murine retroviral bone marrow transplantation models for the study of human myeloproliferative disorders. AB - Human myeloproliferative diseases are common hematologic disorders characterized by clonal overproduction of maturing myeloid or erythroid cells, often caused by expression of a mutant, dysregulated tyrosine kinase (TK). These diseases can be accurately modeled in laboratory mice by the retroviral transfer of a mutant TK gene into murine hematopoietic stem and progenitor cells, followed by transplantation of these cells into irradiated recipient mice. This yields a model system for analyzing the molecular pathophysiology of these conditions and provides a platform for testing therapies, particularly molecularly targeted new chemical entities (NCEs). The Basic Protocol in this unit describes the preparation of mouse bone marrow cells to express the relevant human oncogene before transplanting them into irradiated recipient mice. An alternate protocol describes a similar technique that allows specific induction of lymphoproliferative disease by some TKs. Support protocols for generating and titering retroviral stocks are also included. PMID- 22294221 TI - Animal models of multiple myeloma and their utility in drug discovery. AB - To evaluate potential new therapies and targets for treating multiple myeloma (MM), reproducible, biologically relevant in vivo models are required. Preclinical in vivo models of human MM allow investigators to evaluate novel therapies alone and in combination and quickly translate these results to the clinic where patients directly benefit, whether in the form of a new clinical trial, new doses and schedules, or new drug combinations. Presented in this unit are protocols for generating and maintaining a human extramedullary MM tumor in mice. Additionally, the extramedullary tumor can be excised and digested into a single-cell suspension and the human MM cells injected into mice subcutaneously, intravenously, or intratibially. Once these tumors are generated, they can be used to evaluate novel anti-MM agents and other therapies. PMID- 22294222 TI - Overview of receptor interactions of agonists and antagonists. AB - Historically, the earliest methods used to quantitatively measure the fundamental properties of drugs (namely affinity and efficacy) employed isolated tissues, and it is in this realm that the null methods used to define "receptor pharmacology" were described. This unit describes these methods and their use to specifically classify agonists (through potency ratios and determination of relative affinities and efficacies) and antagonists (through analysis of surmountable and insurmountable antagonism) to yield estimates of potency. Different drugs can yield different behaviors in various tissues, so this unit is centered on a flow diagram to indicate the type of analysis appropriate for the behavior observed. For example, some agonists may be full agonists in some tissues and partial agonists in others, while some antagonists may demonstrate surmountable simple competitive antagonism in some tissues and insurmountable non-competitive antagonism in others. Methods exist for determination of affinity and efficacy for all of these behaviors, and these are delineated in this unit. PMID- 22294223 TI - Models of anxiety: ultrasonic vocalizations of isolated rat pups. AB - Described in this unit is the ultrasonic distress vocalization test in rat pups. This test is a reliable method for detecting anxiolytic properties of test compounds. In this test, ultrasonic vocalizations (30 to 50 kHz) are elicited by separating rat pups of 9 to 11 days of age from their mother and littermates for a brief period of time. The test can be performed under two different stress conditions. Pups are placed in isolation in either a warm (37 degrees C) or cold (18 degrees C) environment for 5 min. The total number and duration of ultrasonic calls emitted by the pups during this period is used as an index of anxiety. Established anxiolytic compounds, including benzodiazepines, serotonin(1A) receptor agonists, and selective serotonin reuptake inhibitors (SSRIs), consistently reduce the number and cumulative duration of these ultrasonic distress vocalizations. PMID- 22294224 TI - Gastrointestinal models: intestinal transit, gastric emptying, and ulcerogenic activity in the rat. AB - The protocols described in this unit are designed to assess the effects of substances on intestinal transit and gastric emptying and to evaluate their ulcerogenic potential on the stomach and duodenum of the rat. Examples of results obtained with atropine or morphine (intestinal transit), loperamide (gastric emptying), or indomethacin (ulcerogenic activity) used as reference substances are provided for illustrative purposes. Atropine and morphine clearly reduce intestinal transit. Atropine, morphine, and loperamide clearly reduce gastric emptying. Indomethacin shows a marked ulcerogenic potential. PMID- 22294225 TI - Orthostatic hypotension induced by postural change in the rat (tilt test). AB - Postural-change-induced (orthostatic) hypotension is defined as an excessive drop in arterial blood pressure occurring when moving toward an upright position. This side effect, which may limit the therapeutic use of some agents, can occur with drugs, such as adrenoceptor blockers and vasodilators, that dampen sympathetic reflex activity. Described in this unit is a procedure for evaluating the effects of test substances on the changes in blood pressure and heart rate that occur in an anesthetized, normotensive rat during a tilting challenge (head-up position). In addition to being a relatively simple technique, this assay yields reproducible orthostatic hypotensive responses and allows for the investigation, in the same preparation, of several ascending doses of a test substance. Examples of results obtained with prazosin, an alpha1-adrenoceptor antagonist that is notorious for causing orthostatic hypotension, are provided for illustrative purposes. PMID- 22294226 TI - Mouse models of bleomycin-induced pulmonary fibrosis. AB - Pulmonary fibrosis is a component of many interstitial lung diseases, including idiopathic pulmonary fibrosis, a chronic, progressive disease for which there is currently no effective therapy. Bleomycin has been widely used in rodents to model pulmonary fibrosis for the study of mechanisms involved in fibrogenesis and for evaluation of potential therapies. Bleomycin induces DNA strand breaks, resulting in pulmonary inflammation, injury, and subsequent interstitial fibrosis. This unit describes methods for delivering bleomycin, either directly into the lung or systemically, to create models of pulmonary fibrosis in rodents. Also described is a rapid and easy procedure for measuring lung collagen content to quantify the severity of fibrosis. PMID- 22294227 TI - Streptozotocin-induced diabetic models in mice and rats. AB - Streptozotocin (STZ) is an antibiotic that can cause pancreatic beta-cell destruction, so it is widely used experimentally as an agent capable of inducing insulin-dependent diabetes mellitus (IDDM), also known as type 1 diabetes mellitus (T1DM). This unit describes protocols for the production of insulin deficiency and hyperglycemia in mice and rats, using STZ. These models for diabetes can be employed for assessing the mechanisms of T1DM, screening potential therapies for the treatment of this condition, and evaluation of therapeutic options. PMID- 22294228 TI - Fear-potentiated startle and light-enhanced startle models in drug discovery. AB - Described in this unit are the fear-potentiated startle (FPS) and light-enhanced startle (LES) tests. These protocols have proven reliable in detecting the anxiolytic properties of test compounds. The principle of these tests is that the magnitude of the acoustic startle reflex is an index of anxiety. The FPS test includes two training sessions in which an intrinsically aversive foot shock is paired with a neutral cue light. In the test session presentation of this cue light is subsequently used to elicit startle potentiation. In the LES test startle reactivity is increased by presentation of bright light. Because LES is based on the innate aversion of rodents for bright light it does not require training sessions. Although LES has been used less frequently than FPS for screening compounds, it has an advantage in that drug effects on startle potentiation are independent of memory retrieval. Further, the contextual anxiety measured in the LES test could be more relevant for pathological anxiety than the conditioned fear associated with the FPS test. PMID- 22294229 TI - Rodent model of attention: the 5-choice serial reaction time task. AB - The 5-choice serial reaction time task (5-CSRTT) is the most widely used test to measure attentional performance in rodents. The basic test design involves training animals to respond to a brief visual stimulus presented unpredictably in one of five locations. Once trained to stable performance levels, the effects of experimental manipulations on response speed and choice accuracy are measured and each are related to attentional performance. Increasingly, the test is also used to examine aspects of response control. Having been adapted from a human task, the test has also been successfully extended to the mouse and primate, thus highlighting its translational value. Increasingly this test is being applied in drug discovery efforts, primarily to identify novel drug treatments for conditions associated with attention deficits. PMID- 22294230 TI - Cardiomyopathic Syrian hamster as a model of congestive heart failure. AB - Cardiomyopathic Syrian hamsters (Bio TO-2 dilated strain) constitute an animal model of congestive heart failure, which progressively develops an alteration of cardiac function leading to decreased arterial blood pressure and musculo cutaneous blood flow associated with a complex process of cardiac remodeling including left ventricle dilation, wall thinning, and greater collagen density. The protocols described in this unit are designed to assess the pharmacological effects of new therapeutic strategies on cardiac and systemic hemodynamics, morphometry (body and target organs weight), cardiac remodeling (left ventricle dilation and collagen density), and survival in this model of dilated cardiomyopathy. Examples of results obtained with enalapril, an angiotensin I converting enzyme inhibitor, are provided for illustrative purposes. PMID- 22294231 TI - Animal models of collagen-induced arthritis. AB - Collagen-induced arthritis in rats is associated with inflammatory polyarthritis, sharing clinical and pathological features with those of human rheumatoid arthritis (RA). Described in this unit is a protocol for consistently inducing arthritis in female Lewis rats by immunizing them with bovine type II collagen (CII) emulsified in complete Freund's adjuvant. This model is of value not only in defining the underlying pathogenesis of RA, but also as a tool for evaluating pharmacological strategies for treating this condition. PMID- 22294232 TI - A model of cystitis pain in the mouse. AB - Interstitial cystitis (IC) is a chronic pelvic-perineal pain syndrome of unknown etiology that mainly targets the lower urinary tract. It is characterized by urinary frequency and urgency, inflammation, stiffening of the bladder wall, and visceral pain. Pain is the most prominent feature of IC and current treatments provide limited relief. To facilitate the identification of novel therapeutic options for IC, efforts are being made to identify more predictive rodent models. A well-characterized rat model is based on administration of cyclophosphamide (CP). The protocol described in this unit replicates this model in mice, demonstrating that CP increases both spontaneous and evoked pain behaviors in this species. This mouse model can be used for understanding disease etiology as well as for the pharmacological evaluation of novel therapeutics for the treatment of IC pain. PMID- 22294233 TI - The Ussing chamber and measurement of drug actions on mucosal ion transport. AB - Ussing chamber technology can be used to investigate the pharmacodynamic and pharmacokinetic properties of drugs and natural substances on polarized epithelia. With this approach, epithelial sheets or confluent epithelial cell monolayers are mounted between two half-chambers, permitting compound delivery to either the apical or basolateral cell surface. Described in this unit are protocols for determining the effects of test compounds on transepithelial ion transport processes. PMID- 22294234 TI - The IND application. AB - Translational biomedical research is often directed to the introduction of a new drug or biologic intended to treat unmet medical need in humans. This unit describes the timing and content of the investigational new drug (IND) application, the primary document required by the U.S. FDA for the initiation of clinical trials in humans with any new chemical entity (NCE) or biologic. The IND application contains all the information necessary for the FDA to make an assessment of the risks and benefits of the proposed clinical trials for the NCE/biologic, containing a detailed but succinct description of the biology, safety, toxicology, chemistry and manufacturing process, and the proposed clinical plan. This unit is geared for those with little or no experience with the IND process and is intended as a global introduction to this, the initial stage of the drug development process for drugs used in humans. PMID- 22294235 TI - Chlorophyllin e4 is a novel photosensitizer against human bladder cancer cells. AB - The aim of the study was to investigate the photodynamic effect of the novel photosensitizer chlorophyllin e4 against human bladder cancer cells. T24 and 5637 bladder cancer cell lines were incubated with chlorophyllin e4 and irradiated with a 650-nm laser light. The controls included cells treated with chlorophyllin e4 but without light as well as cells exposed to laser light without chlorophyllin e4. Photocytotoxicity was monitored with MTT assay and apoptosis was measured by flow cytometry. In addition, confocal laser scanning microscopy was used to assess the subcellular localization of chlorophyllin e4. Chlorophyllin e4 exhibited significant photocytotoxicity in both T24 and 5637 cells, which resulted in a maximum of 82.43 and 85.06% cell death, respectively. Treatment with chlorophyllin e4 or laser light alone did not induce cytotoxicity. In addition, chlorophyllin e4-mediated PDT induced a significantly higher percentage of apoptosis in T24 and 5637 cells compared to the control groups (p<0.01). Moreover, confocal laser scanning microscopy revealed that chlorophyllin e4 co-localized with mitochondria in both cell lines. In conclusion, the remarkable photocytotoxicity, natural abundance and inexpensive composition of chlorophyllin e4 suggest that this compound may be a novel, effective photosensitizer for the treatment of human superficial bladder cancer. PMID- 22294236 TI - Beyond zoster: sensory and immune changes in zoster-affected dermatomes: a review*. AB - Neuroepidermal tropism of varicella-zoster virus accounts for cutaneous and nerve lesions following herpes zoster. Skin lesions heal in a few weeks and may or may not leave visible scars. Nerve lesions involve peripheral sensory fibres, sometimes causing permanent damage that results in partial denervation of the affected dermatome. The effects of the nerve injury involve the sensibility function, thus causing neuralgia, itch, allodynia, hypo- or anaesthesia, as well as the immune function that is related to neuropeptide release, thus altering immune control in the affected dermatome. The neuro-immune destabilization in the zoster-infected site paves the way for the onset of many and various immunity related disorders along the affected dermatome. PMID- 22294237 TI - Management of newly diagnosed patients with type 2 diabetes: what are the attitudes of physicians? A SUBITO!AMD survey on the early diabetes treatment in Italy. AB - Early intensive therapy in type 2 diabetes can prevent complications. Nevertheless, metabolic control is often sub-optimal in newly diagnosed patients. This web-based survey aimed to evaluate opinions of physicians about treatment, priorities, and barriers in the care of patients first referred to diabetes clinics. Data on physician attitudes toward therapeutic preferences for two clinical case models (same clinical profile, except HbA1c levels of 8.6 and 7.3% at the first access, respectively) were collected. Participants were asked to rank from 1 (most important) to 6 (least important) a list of priorities and barriers associated with the care of new patients. Overall, 593 physicians participated. In both case models, metformin and education were primary options, although their combination with other classes of drugs varied substantially. Main priorities were "to teach the patient how to cope with the disease" and "to achieve HbA1c target"; main barriers were "lack of time" and "long waiting list". At multivariate analyses, physicians from the South of Italy had a twofold higher likelihood to attribute a rank 1-2 to organizational barriers than those operating in the North (South vs. North: OR: 2.4; 95% CI 1.4-4.1; Center vs. North: OR: 2.4; 95% CI 0.9-3.2). In the absence of a widely accepted evidence based therapeutic algorithm driving the therapeutic choices according to the patient characteristics, prescriptions vary according to physician preferences. Education is perceived as a key-strategy, but organizational barriers and geographic disparities are an obstacle. These findings can drive new strategies to reduce clinical inertia, attitudes variability, and geographic disparities. PMID- 22294238 TI - Predictors of response to ziprasidone: results from a 6-week randomized double blind, placebo-controlled trial for acute depressive mixed state. AB - INTRODUCTION: The present study is aimed at investigating possible predictors of response to ziprasidone in a sample of patients with mixed depressive state. METHODS: 72 patients were randomized to either ziprasidone or placebo and treated prospectively for 6 weeks. The clinical response and remission were defined with various clinical variables including Montgomery Asberg Depression Rating Scale. Further outcome measures included predictors of remission and other clinical variables over time. RESULTS: None of the variables under investigation were significantly associated with response or remission at 6 weeks (all p values>0.003, respectively). CONCLUSIONS: Further investigations are warranted due to clear limitations, mostly small sample size and use of concomitant medications. PMID- 22294240 TI - [Medicinal therapy of metastasized neuroendocrine tumors of the gastroenteropancreatic system.] AB - Neuroendocrine neoplasms of the gastroenteropancreatic system are classified according to the WHO classification system 2010 into neuroendocrine tumors (NET) and neuroendocrine carcinomas (NEC). The proliferation index Ki-67 and the grading of NETs is essential for the prognosis and therapy plan. Also NET tumor biology and therapeutic options may differ depending on the primary NET tumor location. Palliative therapy of inoperable NETs involves local ablative methods in cases of primary liver metastasis, peptide receptor radionuclide therapy (PRRT) in NETs expressing somatostatin receptors and different options for medicinal therapy. This manuscript reviews the current role of biotherapy with somatostatin analogues and interferon-alpha for symptom and tumor control. In addition conventional chemotherapy regimens and novel molecular targeted therapeutic options, such as sunitinib or everolimus in NET of the pancreas are reviewed. Possible therapeutic algorithms are discussed. PMID- 22294241 TI - Double negative regulatory T cells in transplantation and autoimmunity: recent progress and future directions. AB - T lymphocytes bearing the alphabeta T cell receptor (TCR) but lacking CD4, CD8, and markers of natural killer (NK) cell differentiation are known as 'double negative' (DN) T cells and have been described in both humans and rodent models. We and others have shown that DN T cells can act as regulatory T cells (Tregs) that are able to prevent allograft rejection, graft-versus-host disease, and autoimmune diabetes. In the last few years, new data have revealed evidence of DN Treg function in vivo in rodents and humans. Moreover, significant advances have been made in the mechanisms by which DN Tregs target antigen-specific T cells. One major limitation of the field is the lack of a specific marker that can be used to distinguish truly regulatory DN T cells (DN Tregs) from non-regulatory ones, and this is the central challenge in the coming years. Here, we review recent progress on the role of DN Tregs in transplantation and autoimmunity, and their mechanisms of action. We also provide some perspectives on how DN Tregs compare with Foxp3(+) Tregs. PMID- 22294242 TI - Effect of radiation on the expression of osteoclast marker genes in RAW264.7 cells. AB - Cancer radiation therapy can cause skeletal complications, such as osteopenia and osteoporosis. To understand the mechanism responsible for the skeletal complications, the expression profiles of osteoclast marker genes in RAW264.7 cells were observed. Osteoclast formation was established by RAW264.7 cells that were treated with the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) and detected using immunochemistry and morphological observations. Quantitative real-time polymerase chain reaction was used to assess the expression of a panel of osteoclast markers, including the receptor activator of NF-kappaB (RANK), tartrate-resistant acid phosphatase (TRAP), integrin beta3 and the calcitonin receptor (CTR). RANKL-induced osteoclasts were TRAP-positive and multinucleated, and displayed a distinct morphology. RANKL-induced osteoclast precursor cells had increased TRAP and RANK expression and decreased CTR expression compared to the control cells not treated with RANKL. RAW264.7 cells irradiated with 2-Gy gamma-rays had upregulated integrin beta3 and RANK expression and downregulated CTR expression compared to the control RAW264.7 cells. The effect of radiation on RANKL-induced osteoclast differentiation enhanced the expression of CTR and inhibited the expression of RANK and TRAP. Therefore, radiation damage from 2-Gy gamma-rays can promote the activities of osteoclast precursor cells, but not those of osteoclasts. PMID- 22294243 TI - Orientational ordering of the second layer of C60 molecules on Au(111). AB - We have studied the orientational ordering of the second layer of C(60) molecules on Au(111) using scanning tunnelling microscopy (STM) at 77 K. The orientation of individual molecules within the second layer follows a regular pattern, giving rise to a 2 * 2 superlattice. The long-range order of the 2 * 2 lattice depends on the structure of the first molecular layer with the best ordering found inside the R14 degrees domain. The second layer formed on top of the contrast disordered R30 degrees domain consists of patches of bright and dim molecules. The contrast between bright and dim patches shows a clear dependence on the sample bias. This bias-dependent contrast is explained by considering the contributions to tunnel current from HOMO and LUMO mediated electron transfer processes. Scanning tunnelling spectroscopic measurement reveals the narrowing of the HOMO-LUMO gap for the layer of molecules in direct contact with the Au(111) substrate. PMID- 22294244 TI - Diarylethene doped biocompatible polymer dots for fluorescence switching. AB - The photochromic molecule diarylethene works as a "toggle switch" for biocompatible fluorescence polymer dots and enables fluorescence switching in biological samples. PMID- 22294245 TI - Post-treatment Lyme disease syndrome symptomatology and the impact on life functioning: is there something here? AB - PURPOSE: A subset of patients treated for Lyme disease report persistent or recurrent symptoms of unknown etiology named post-treatment Lyme disease syndrome (PTLDS). This study aims to describe a cohort of participants with early, untreated Lyme disease, and characterize post-treatment symptomatology and functional impact of PTLDS over time. METHODS: Sixty-three participants with erythema migrans and systemic symptoms were enrolled in a prospective cohort study. Participants underwent physical exams and clinical assessments, and completed the SF-36 (daily life functioning) and the Beck Depression Inventory, Second Edition (BDI-II) (depression), at each of five visits over a period of 6 months. RESULTS: Signs of Lyme disease disappeared post-treatment; however, new onset patient-reported symptoms increased or plateaued over time. At 6 months, 36% of patients reported new-onset fatigue, 20% widespread pain, and 45% neurocognitive difficulties. However, less than 10% reported greater than "minimal" depression across the entire period. Those with PTLDS (36%) did not differ significantly from those without with respect to demographics, pre treatment SF-36, and BDI-II scores. Statistically significant differences were found over time on the Role Physical, Vitality, Social Functioning, Role Emotional, and Mental Health subscales (with a trend toward significance for the remaining three subscales of Physical Functioning, Bodily Pain, and General Health) of the SF-36 between those with an eventual PTLDS diagnosis and those without when measured at 6 months. CONCLUSIONS: Unlike clinical signs of Lyme disease, new-onset symptoms are reported by a subset of participants without evidence of depressive symptomatology. Patients who developed PTLDS had significantly lower life functioning compared to those without PTLDS. We propose future avenues for researching infection-triggered symptoms resulting from multiple mechanisms. PMID- 22294246 TI - [Parental administration of unprescribed antimalarial drugs to treat febrile children in Gabon]. AB - Resistance by Plasmodium falciparum to antimalarial drugs has strongly hampered strategies for malaria control and elimination. Therefore, one of the goals of the World Health Organisation's new malaria control strategies is the rational and appropriate use of antimalarial drugs and in particular of artemisinin-based combination therapy (ACTs), currently used for the treatment of uncomplicated malaria; in order to delay the appearance of drug-resistant parasites. The unprescribed use of antimalarial drugs (self medication and parental administration to children) is a key component in the development of antimalarial drug resistance and must be controlled among patients living in malaria-endemic areas. The aim of our study was to estimate the frequency of this parental administration among febrile children and to identify the specific drugs used. Data were collected in two studies evaluating the proportion of malaria cases and the performance of rapid drug tests among febrile children seen in 2008-2009 at 3 hospitals, one in a rural area, one in an urban area, and the third in a semi urban area. This parental medication administration was found among 21.4% of the 2543 children included in the studies. It was most common at the rural hospital (29%), which is also where malaria prevalence was highest (39%). Of the 548 children "medicated", 421, that is, almost 80%, were not infected. The antimalarial drugs used most frequently were ACTs (43.8%) and quinine (12%). In Gabon, as in other sub-Saharan countries, use of antimalarial drugs before consultation is common and is an obstacle to malaria control. Therefore, improving the rational use of these drugs by the population requires active outreach to the community about the risks of unprescribed medication. PMID- 22294247 TI - Effects of the antimalarial drugs ferroquine and artesunate on Plasmodium yoelii yoelii gametocytegenesis and vectorial transmission. AB - Chemistry still has a role in the management of malaria, alongside the mosquito netting soaked in insecticide that is used increasingly, as we continue to await the long anticipated vaccine. During its cycle, the hematozoon parasite develops through three major periods. The first, malarial infection, corresponds to the intrahepatic development of infective forms from the mosquito vector; this period is not sensitive to treatment and is often asymptomatic. The period of erythrocytic schizogony is the most urgent, and treatment activity is primordial. Finally, the phase of sexual reproduction, when gametocytes develop within the erythrocytes ensures the perpetuation of the species when these reach the blood feeding female anopheles mosquitoes. The aim of our work was to study the effect on gametocytes of drugs known to be effective on the asexual blood forms of the protozoan and thus the potential repercussions on malaria transmission. This experimental study was conducted with an animal model whose parasite cycle and modes of transmission are close to those of human malaria: Plasmodium yoelii, maintained on Swiss mice, with the Anopheles stephensi vector (maintained in an animal facility at the National Museum of Natural History in Paris). Two drugs were tested: ferroquine (a chloroquine derivative with a ferrocene molecule at the lateral carbon chain that restores its efficacy against chloroquine-resistant strains) and artesunate (a derivative of artemisinin, from ginghao, a Chinese plant also known as artemisia annua, or sweet wormwood), a treatment of choice in the combined therapies recommended by WHO. The efficacy of these drugs, prescribed at doses subcurative for the asexual forms, were tested against gametocyte production, quantitatively by counting them in the blood and qualitatively by counting the quantity of oocysts developed on the mosquito's midgut, which are indicators of gametocyte activity. The mice that were parasite infected and then treated served as their own controls: lots of 30 mosquitoes fed on each mouse before treatment and then 90 minutes and 5 hours after treatment. Quantitatively, the comparison of the blood parasite level and the gametocyte index shows that treated mice had a higher level of circulating gametocytes than untreated parasite infested mice, regardless of drug or dose (5 or 10 mg/kg). For artesunate at 5 mg/kg, we noted that the blood gametocyte level was almost double that of the controls. On the other hand, qualitatively, the first results obtained with optical and electronic microscopy showed morphologic alterations of the circulating gametocytes (pigment clumping and lateralisation within red blood cells) and reduced infectivity of the gametocytes for the mosquitoes that fed at 1 and 5 hours after treatment. We were able to demonstrate statistically that the infectivity of gametocytes, measured by the quantity of oocysts counted in the mosquito midgut, was reduced by 70% for those treated with ferroquine and by 85% for those from mice treated by artesunate. Complementary studies will seek to specify the populations (age) of gametocytes damaged by treatment and the importance and nature of their morphologic alterations. PMID- 22294248 TI - [Hematologic and immunologic signs of lupus: the experience of the hospital of Dakar]. AB - INTRODUCTION: The systemic erythematosus lupus (SEL) or lupic disease is a systemic auto-immune pathology, characterized primarily by the presence of antibodies directed against native antibodies anti-DNA. The circumstances of discovery are variable and polymorphic. The hematologic signs and the immunological disorders constitute criteria of diagnosis of lupic disease. METHODOLOGY: It is a multicentric retrospective study from January 1, 1997 to September 30, 2006. Patients were followed up in Internal medicine of Dakar. We appreciate the hematologic and immunological aspects appreciate their prognosis prevalence and their implications with the course the lupic disease. RESULTS: 142 lupic patients were included with 125 women and 17 men; the sex ratio is 0.13. The average age was 34 years with extremes of 6 and 72 years. Our patients had hematologic manifestations average in 32,4 % of the cases and immunological in 76,8 % of the cases. The immunological tests showed the presence, of antinuclear antibodies in 97,9 % of the cases, of native antibody anti-DNA in 45,7 % of the cases, the anti-ECT in 86,95 % (with the anti-RNP in 78,3 % of the cases, anti-Sm in 56,5 % and of anti-SSA in 87 % of the cases). Antibodies anti-DNA and anti-ECT were associated with the hematologic demonstrations respectively in 92,0 % and 95 % of the cases (p = 0,08). Total survival in 96 % of the cases is estimated to 7 years. CONCLUSION: The circumstances of discovery of the lupic disease are variable. The hematologic signs constitute criteria diagnosis of lupic disease. The accessibility of the hematologic and immunological assessment is necessary for an early diagnosis and an early treatment. PMID- 22294249 TI - [Consumption of addictive substances by Gabonese teenagers: an epidemiological survey]. AB - OBJECTIVE: To study the characteristics of the consumption of addictive substances by adolescents in Gabon. POPULATION AND METHODS: For this cross sectional, descriptive study, we used an anonymous questionnaire to collect information from 1469 adolescents aged 10 to 19 years in six cities in Gabon during 2008. RESULTS: Alcohol was the addictive substance most often consumed (55.5%), followed by tobacco (21.5%) and illegal drugs (5%). In all, 47.6% of the teenagers reported having already been drunk. Combined consumption of these different substances was reported by 44.5%. CONCLUSION: Our results show the extent of the consumption of addictive substances among adolescents in Gabon and the existence of groups at risk of addiction and abuse. Prevention strategies must be set up. PMID- 22294250 TI - [Diffuse cervico-facial cellulitis: 32 cases in Libreville]. AB - OBJECTIVE: The aim of this study was to analyze the predisposing factors and the diagnostic and therapeutic aspects of diffuse cervico-facial cellulitis. MATERIAL AND METHODS: This retrospective study examined the records of all 32 patients admitted to the ENT and cervico-facial department of the Omar Bongo Ondimba Army Teaching Hospital in Libreville with diffuse cervico-facial cellulitis, from January 2006 through December 2010. RESULTS: The study included 18 women (56%) and 14 men (44%) with a mean age of 28 years. At admission, 28 patients (87.5%) had already received anti-inflammatory drugs and 25 (78%) one or more antibiotics. Two patients were HIV+. The main route was dental for 21 patients (66%), tonsillar for 4 (13%), submandibular for 2 (6%), parotid for 2 cases (6%), cutaneous for 1 (3%) and unspecified in 2 more (6%). The cellulitis was pseudo phlegmonous in 24 patients (75%) and gangrenous in 8 cases (25%). It extended to the mediastinum in six patients (19%). The bacteriological study, carried out in 24 cases (75%), found 14 cases of aerobic germs. Medical or medical and surgical treatment led to cure for 30 patients (94%). Two patients (6%) died. CONCLUSION: Treatment of cervico-facial cellulitis must be early and multidisciplinary. Self medication with anti-inflammatory drugs for bucco-pharyngeal infections without appropriate antibiotic treatment is the principal predisposing factor. PMID- 22294251 TI - [Prevalence and etiology of amblyopia of children in Yaounde (Cameroon), aged 5 15 years]. AB - PURPOSE: To determine the frequency of amblyopia and identify its causes in a population of children aged 5-15 years in Cameroon. SUBJECTS AND METHODS: This retrospective study examined the files of children aged 5-15 years seen in a private eye clinic in Yaounde from January 2008 through December 2010. The subjects underwent a complete ophthalmic examination including assessment of the best corrected visual acuity on a LogMAR chart, cycloplegic refraction measurements, and an orthoptic examination. The slit-lamp microscope and eye fundus examinations made it possible to rule out organic diseases. Statistical analysis was performed with Epi Info software, version 3.5.3, to analyze the the frequency and laterality of amblyopia according to age, sex, and refractive errors. RESULTS: Twenty-eight of the 314 patients studied had amblyopia, for a frequency of 8.9 % in the study population and 10.3 % in the subjects with ametropia (n = 271). The average age of children with amblyopia was 9.9 + / - 3 years. The frequency of amblyopia was higher among boys, but the difference was not statistically significant (p=0.3679). In order of frequency, the causes were refractive errors, for 93 % (26/28) of the children, and strabismus for 7 % (2/28). Astigmatism was the most frequent cause of ametropic amblyopia. Amblyopia had an anisometropic origin in 43 % (12/28) of cases. It was unilateral in 39.2 % (11/28) and bilateral in 61 % (17/28) of cases, severe in 18 %, moderate in 18 %, and mild in 64 %. CONCLUSION: Ten percent of the subjects in our series had amblyopia, mainly due to refractive errors. Amblyopia was most frequently bilateral and mild. A systematic ophthalmological examination in childhood could provide early detection and management of refractive errors that cause ocular morbidity. PMID- 22294252 TI - [Cervical lymph node tuberculosis in Libreville: epidemiology, diagnosis, and therapy]. AB - OBJECTIVES: To analyse the epidemiological, diagnostic and therapeutic aspects of cervical lymph node tuberculosis (TB) in Libreville. MATERIAL AND METHODS: This retrospective descriptive multicentre study included all 140 patients with complete files who were treated for cervical lymph node TB from 2001 through 2006, regardless of whether TB was found at any other site. RESULTS: A slight predominance of men was observed. The infected lymph nodes were most often located at the posterior triangle of the neck. Histological proof was obtained for 81 patients. We recorded 94 cures, 4 cases of therapeutic failure, 34 patients lost to follow-up and 8 deaths. CONCLUSION: Cervical lymph node tuberculosis is a common ailment. Excisional lymph node biopsy has a twofold interest -therapeutic and diagnostic. It is based on histological examination, which must henceforth be systematic. Tuberculosis is a major HIV-related opportunistic infection and must be screened for or monitored at every HIV check up. PMID- 22294253 TI - [Malaria and HIV infection in subSaharan Africa: another match made in hell?]. AB - Malaria and HIV are the most important infections in subSaharan Africa, in terms of the morbidity and mortality they cause. Current data suggest a possible interaction between the two diseases. Cellular immunodeficiency due to HIV infection might increase the frequency and severity of malaria, as local populations in endemic areas become less resistant. Likewise, the onset and repetition of malaria episodes might activate HIV replication and thus decrease the number of CD4 lymphocytes and accelerate the disease course. Despite their geographical coincidence, the epidemiological profiles of malaria and HIV differ considerably. The entanglement of these two diseases has epidemiological, clinical and therapeutic consequences in subSaharan Africa that raise concerns that HIV with malaria, as with tuberculosis, is a match made in Hell. PMID- 22294254 TI - [Leadership and vision in the improvement of universal health care coverage in low-income countries]. AB - In Burkina Faso, as in most developing countries, the operational level of the health system is made up of Health Districts (HDs), the activities of which are typically coordinated by the District Team (DT). Assessing the the core functions of DTs, as described by WHO, shows two important weaknesses. Firstly, instructions from "above" are often implemented rather passively: DTs tend not to display much leadership. Secondly, the current organisation, based on input financing and centralised planning, does not sufficiently promote either the vision or research functions of DTs. In this article, we report our experience in the Orodora HD in Burkina Faso, where the DT's leadership and vision proved to be essential ingredients for effective health action in the district. Our description of six interventions implemented between 2004 and 2008 shows how DT leadership and vision have improved outputs at the HD level. Until 2004, the district applied static health planning. The health system was insufficiently financed and performed poorly. Faced with this situation, the DT decided to set up several priority interventions based on health care access criteria and patient concerns, while respecting and contextualizing national norms and objectives. Six interventions were then implemented. The first was ensure that quality blood (meeting transfusion security norms) was available at the District Hospital (DH), by picking blood up from the regional blood transfusion center weekly. This speeded up care at the DH, reduced the number of cases referred to the regional hospital for transfusion, and reduced neonatal and maternal mortality. The second intervention sought to improve the skills of health workers in managing emergency cases and to improve relationships with the referral hospital through the reintroduction of counter-referral procedures. This led to a decrease in unnecessary referrals and also reduced the mortality rates of serious cases. The third intervention, by implementing a decentralized approach to tuberculosis detection, succeeded in improving access to care and enabled us to quantify the rate of tuberculosis-HIV co-infection in the HD. The fourth intervention improved financial access to emergency obstetric care by providing essential drugs and consumables for emergency obstetric surgery free of charge. The fifth intervention boosted the motivation of health workers by an annual 'competition of excellence', organised for workers and teams in the HD. Finally, our sixth intervention was the introduction of a "culture" of evaluation and transparency, by means of a local health journal, used to interact with stakeholders both at the local level and in the health sector more broadly. We also present our experiences regularly during national health science symposia. Although the DT operates with limited resources, it has over time managed to improve care and services in the HD, through its dynamic management and strategic planning. It has reduced inpatient mortality and improved access to care, particularly for vulnerable groups, in line with the Primary Health Care and Bamako Initiative principles. This case study would have benefited from a stronger methodology. However, it shows that in a context of limited resources it is still possible to strengthen the local health system by improving management practices. To progress towards universal health coverage, all core functions of a DT are worth implementing, including leadership and vision. National and international health strategies should thus include a plan to provide for and train local health system managers who can provide both leadership and strategic vision. PMID- 22294255 TI - A phase II study of capecitabine, oxaliplatin, and cetuximab with or without bevacizumab as frontline therapy for metastatic colorectal cancer. A Fox Chase extramural research study. AB - OBJECTIVES: Dual inhibition of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) demonstrated initial promise in clinical trials. This phase II study tested the efficacy and safety of capecitabine, oxaliplatin, and cetuximab with or without bevacizumab as first-line treatment for metastatic colorectal cancer patients. METHODS: Patients were randomized to receive capecitabine 850 mg/m2 PO twice daily for 14 days, oxaliplatin 130 mg/ m2 IV day 1, and cetuximab 400 mg/m2 IV loading dose followed by 250 mg/m2 IV days 1, 8, and 15 with (arm A) or without (Arm B) bevacizumab 7.5 mg/kg IV day 1 every 21 days. Tumor samples were collected and retrospectively analyzed for KRAS mutation status. The primary endpoint was response rate, with time to progression (TTP) and overall survival (OS) as secondary objectives. RESULTS: Twenty-three patients (12 in arm A, 11 in arm B) were enrolled onto the study. Median follow up was 25.9 months. Both treatments were well tolerated, with expected higher rates of grade 1/2 hypertension and bleeding in arm A. The overall response rate was 54% (36.4% in arm A and 72.7% in arm B). Median time to progression was 8.7 months in arm A and 14.4 months in arm B. The median survival was 18.0 months in arm A and 42.5 months in arm B. The study was prematurely terminated after other studies reported inferior outcomes with dual antibody therapy. CONCLUSIONS: Although terminated early, the study supports the detrimental effect of combining VEGF and EGFR inhibition in metastatic colorectal cancer. PMID- 22294256 TI - Properties of antibodies to a synthetic peptide representing an epitope shared by receptors of the type I cytokine family. AB - Previous works from our laboratory demonstrated that the monoclonal antibody (MAb) called R7B4 is directed to an epitope shared by various receptors corresponding to the type I cytokine receptor family, containing the common motif WSXWS or the homologous F(Y)GEFS. Later a consensus peptide significantly recognized by the MAb was identified and synthesized (sequence HGYWSEWSPE). In the present work, an homologous of the consensus sequence (HHGYWSEWSPE) was conjugated to PADRE adjuvant to produce Ab that could simulate theMAb activity, that is, acting as hormone and/or cytokine antagonists. The covalently conjugated peptide-PADRE was a better immunogen than the consensus peptide alone according to the reactivity of sera from C57BL/6 immunized mice and, besides, no Ab to PADRE were detected. Furthermore, Ab to consensus peptide elicited after peptide PADRE inoculation into mice behaved as immunomodulatory agents, since they improved the humoral response to a foreign antigen (in this case ovalbumin). In addition, the Ab inhibited the in vitro proliferation of various cell lines, mainly cells derived from human and mouse breast cancer. Thus, immunization with the conjugate peptide-PADRE prepared under the experimental conditions described herein originated immunomodulatory Ab that, in the future, could be tested in some pathological conditions. PMID- 22294257 TI - Neural correlates of stress-induced and cue-induced drug craving: influences of sex and cocaine dependence. AB - OBJECTIVE: Although stress and drug cue exposure each increase drug craving and contribute to relapse in cocaine dependence, no previous research has directly examined the neural correlates of stress-induced and drug cue-induced craving in cocaine-dependent women and men relative to comparison subjects. METHOD: Functional MRI was used to assess responses to individualized scripts for stress, drug/alcohol cue and neutral-relaxing-imagery conditions in 30 abstinent cocaine dependent individuals (16 women, 14 men) and 36 healthy recreational-drinking comparison subjects (18 women, 18 men). RESULTS: Significant three-way interactions between diagnostic group, sex, and script condition were observed in multiple brain regions including the striatum, insula, and anterior and posterior cingulate. Within women, group-by-condition interactions were observed involving these regions and were attributable to relatively increased regional activations in cocaine-dependent women during the stress and, to a lesser extent, neutral relaxing conditions. Within men, group main effects were observed involving these same regions, with cocaine-dependent men demonstrating relatively increased activation across conditions, with the main contributions from the drug and neutral-relaxing conditions. In men and women, subjective drug-induced craving measures correlated positively with corticostriatal-limbic activations. CONCLUSIONS: In cocaine dependence, corticostriatal-limbic hyperactivity appears to be linked to stress cues in women, drug cues in men, and neutral-relaxing conditions in both. These findings suggest that sex should be taken into account in the selection of therapies in the treatment of addiction, particularly those targeting stress reduction. PMID- 22294258 TI - Striatal dopamine transporter alterations in ADHD: pathophysiology or adaptation to psychostimulants? A meta-analysis. AB - BACKGROUND: Striatal dopamine transporter abnormalities are thought to underlie the pathophysiology and psychostimulant treatment of attention deficit hyperactivity disorder (ADHD). However, individual studies using single photon emission tomography (SPECT) or positron emission tomography (PET) have yielded inconsistent results, i.e., both high and low striatal dopamine transporter levels. METHOD: Nine SPECT and PET studies investigating striatal dopamine transporter density in ADHD patients (N=169) and age-, gender-, and IQ-matched healthy comparison subjects (N=173) were included in a quantitative meta analysis. Binding potentials in the striatum and demographic, clinical, and methodological variables were extracted from each publication or obtained directly from authors. Hedges' g was used as a measure of effect size in an analysis using Comprehensive Meta-Analysis software. Publication bias was assessed with funnel plots and Egger's intercept. Heterogeneity was addressed with the Q statistic and I2 index. RESULTS: Striatal dopamine transporter density was 14% higher on average in the ADHD group than in the healthy comparison group. However, heterogeneity across studies was large and statistically significant. Meta-regression analyses showed that the percentage of subjects without exposure to psychostimulants was negatively correlated with dopamine transporter density; density was higher in patients with previous medication exposure and lower in medication-naive patients. There was no moderating effect for age, comorbidity, gender, year of publication, or imaging technique. There was no publication bias, and sensitivity analysis confirmed robustness of the results. CONCLUSIONS: Striatal dopamine transporter density in ADHD appears to depend on previous psychostimulant exposure, with lower density in drug-naive subjects and higher density in previously medicated patients. PMID- 22294259 TI - Relationship between serum undercarboxylated osteocalcin and hyaluronan levels in patients with bilateral knee osteoarthritis. AB - Serum undercarboxylated osteocalcin (s-ucOC) is a marker for vitamin K metabolism (deficiency). The aim of this study was to investigate the serum levels of ucOC in patients with bilateral knee osteoarthritis (K-OA), and the correlation between ucOC and other biomarkers for K-OA. A total of 25 patients (22 women, 3 men, mean age 76.0+/-7.8, range 54-88 years, mean BMI 24.9+/-4.7) with a Kellgren Lawrence grade of 3 or 4 for bilateral knee were enrolled in this study. The levels of s-ucOC and other biomarkers were measured. The levels of s-ucOC (5.66+/ 4.70 ng/ml) as well as other cartilage metabolism markers, were elevated in the patients; however, bone metabolism markers were within the normal ranges. Of interest, there was a significant correlation between s-ucOC and serum hyaluronan (a marker for synovitis) (P<0.05). Our findings suggest that vitamin K metabolism may be associated with synovitis in patients with K-OA, and s-ucOC could be a biomarker for K-OA. PMID- 22294260 TI - Differential response of arterial and venous endothelial cells to extracellular matrix is modulated by oxygen. AB - Binding of endothelial cell (EC) integrins to extracellular-matrix (ECM) components is one of the key events to trigger intracellular signaling that will ultimately result in proper vascular development. Even within one tissue, the endothelial phenotype differs between arteries and veins. Here, we tested the hypothesis that anchorage dependent processes, such as proliferation, viability, survival and actin organization of venous (VEC) and arterial EC (AEC) differently depend on ECM proteins. Moreover,because of different oxygen tension in AEC and VEC, we tested oxygen as a co-modulator of ECM effects. Primary human placental VEC and AEC were grown in collagens I and IV, fibronectin, laminin, gelatin and uncoated plates and exposed to 12 and 21% oxygen. Our main findings revealed that VEC are more sensitive than AEC to changes in the ECM composition. Proliferation and survival of VEC, in contrast to AEC, were profoundly increased by the presence of collagen I and fibronectin when compared with gelatin or uncoated plates. These effects were reversed by inhibition of focal adhesion kinase (Fak) and modulated by oxygen. VEC were more susceptible to the oxygen dependent ECM effects than AEC. However, no differential ECM effect on actin organization was observed between the two cell types. These data provide first evidence that AEC and VEC from the same vascular loop respond differently to ECM and oxygen in a Fak-dependent manner. PMID- 22294261 TI - Untypical connectivity from olfactory sensory neurons expressing OR37 into higher brain centers visualized by genetic tracing. AB - The OR37 subfamily of odorant receptors(ORs) exists exclusively in mammals. In contrast to ORs in general, they are highly conserved within and across species.These unique features raise the question, whether olfactory information gathered by the OR37 sensory cells is processed in specially designated brain areas. To elucidate the wiring of projection neurons from OR37 glomeruli into higher brain areas, tracing experiments were performed.The application of DiI onto the ventral area of the olfactory bulb, which harbors the OR37 glomeruli, led to the labeling of fibers not only in the typical olfactory cortical regions,but also in the medial amygdala and the hypothalamus. To visualize the projections from a defined OR37 glomerulus more precisely, transgenic mice were studied in which olfactory sensory neurons co-express the receptor subtype OR37C and the transsynaptic tracer wheat germ agglutinin(WGA). WGA became visible not only in the OR37C sensory neurons and the corresponding OR37C glomerulus,but also in cell somata located in the mitral/tufted cell layer adjacent to the OR37C glomerulus, indicating a transfer of WGA onto projection neurons. In the brain, WGA immunoreactivity was not detectable in typical olfactory cortical areas, but instead in distinct areas of the medial amygdala.Detailed mapping revealed that the WGA immunoreactivity was restricted to the posterior-dorsal subnucleus of the medial amygdala. In addition, WGA immunoreactivity was visible in some well circumscribed areas of the hypothalamus.These results are indicative for a unique connectivity from OR37C sensory cells into higher brain centers. PMID- 22294262 TI - Impaired expression of Tim-3 on Th17 and Th1 cells in psoriasis. AB - Psoriasis is a chronic skin disease mediated by Th17 and/or Th1 cells. Tim-3 is a cell surface molecule preferentially expressed on Th17 and Th1 cells. The interaction of Tim-3 with Tim-3 ligand inhibits cytokine production. To assess whether T cells in psoriasis have functional abnormalities, expression of cell surface Tim-3 on blood T cells producing interleukin-17 (Th17/Tc17 cells) or interferon-gamma (Th1/Tc1 cells) was examined by flow cytometry. Psoriasis patients had higher numbers of Th17 and Tc17 cells, as well as Th1 and Tc1 cells, than healthy donors. However, Th17, Th1 and Tc1 cells in psoriasis did not efficiently express Tim-3 upon activation, compared with those from atopic dermatitis and healthy donors. Tim-3- cells showed more potent cytokine production than Tim-3+ cells. Impaired Tim-3 expression allows Th17, Th1 and Tc1 cells to escape from Tim-3-mediated negative regulatory systems and may contribute to the pathogenesis of psoriasis. PMID- 22294263 TI - Three new diterpenoids from the leaves of Thuja orientalis. AB - Three new diterpenoids, 18-formyloxy-8 beta-hydroxysandaracopimar-15-ene (1), 15(R)-N-butoxypinusolidic acid (2), and 15,16-dihydro-15,16-dimethoxylambertianic acid (3), along with twelve known compounds (4-15) were isolated from MeOH extracts of leaves of Thuja orientalis L. The structures of the three new compounds were elucidated on the basis of spectroscopic analyses, including extensive 2D-NMR data. The absolute stereochemistry of compound 2 was clarified by a CD spectroscopic study. The isolated compounds were evaluated for cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines in vitro using the sulforhodamin B (SRB) bioassay. PMID- 22294264 TI - HPLC-based activity profiling--discovery of sanggenons as GABAA receptor modulators in the traditional Chinese drug Sang bai pi (Morus alba root bark). AB - EtOAc extracts from two batches of Morus alba root bark (Sang bai pi) potentiated gamma-aminobutyric acid (GABA)-induced chloride influx in Xenopus oocytes, which transiently expressed GABA (A) receptors of the subunit composition alpha1beta2gamma(2S). With the aid of HPLC-based activity profiling of the extract from the first batch, activity was traced to a peak subsequently identified as sanggenon G (3). The second batch had a different phytochemical profile, and HPLC-based activity profiling led to the identification of sanggenon C (4) and a stereoisomer of sanggenon D (2) as positive GABA (A) receptor modulators. The structurally related compound kuwanon L (1) was inactive. The sanggenons represent a new scaffold of positive GABA (A) receptor modulators. PMID- 22294265 TI - Synthesis of amine-functionalized heparin oligosaccharides for the investigation of carbohydrate-protein interactions in microtiter plates. AB - The synthesis of well-defined oligosaccharides is crucial for the establishment of structure-activity relationships for specific sequences of heparin, contributing to the understanding of the biological role of this polysaccharide. It is highly convenient that the synthetic oligosaccharides contain an orthogonal functional group that allows selective conjugation of the probes and expands their use as chemical tools in glycobiology. We present here the synthesis of a series of amine-functionalized heparin oligosaccharides using an n+2 modular approach. The conditions of the glycosylation reactions were carefully optimized to produce efficiently the desired synthetic intermediates with an N benzyloxycarbonyl-protected aminoethyl spacer at the reducing end. The use of microwave heating greatly facilitates O- and N-sulfation steps, avoiding experimental problems associated with these reactions. The synthesized oligosaccharides were immobilized in 384-well microtiter plates and successfully probed with a heparin-binding protein, the basic fibroblast growth factor FGF-2. The use of hexadecyltrimethylammonium bromide minimized the amount of sugar required for attachment to the solid support. Using this approach we quantified heparin-protein interactions, and surface dissociation constants for the synthetic heparin derivatives were determined. PMID- 22294266 TI - Pre-neoplastic lesion, mucin-depleted foci, reveals de novo high-grade dysplasia in rat colon carcinogenesis. AB - Aberrant crypt foci (ACF) and mucin-depleted foci (MDF) have recently been recognized as pre-neoplastic lesions in the colon of carcinogen-treated rodents. In the present study, we analyzed the sequential development of ACF and MDF histopathologically in the colon of rats from 5 to 40 weeks after DMH treatment. The numbers of ACF per colon increased over time during the experiment, and were much higher than the number in tumors, while the number of MDF per colon remained unchanged from the early stage (the 5th week after carcinogen exposure), and approximate to those in tumors. The incidence of ACF, which was much higher than that of tumors, also increased gradually in a time-dependent manner. The incidence of MDF, however, was similar to that of tumors and did not change significantly during the whole experiment. No lesion as dysplasia with high-grade (DHG) or adenocarcinoma (AC) were found in any large ACF from the 5th to 40th week histopathologically, whereas all of the large MDF showed DHG or AC features. Even at 5 weeks, MDF showed features of DHG. We classified these into two forms of MDF: flat and protruded MDF. At 40 weeks, the number of flat MDF per colon decreased significantly compared with that at 20 weeks (p<0.05), however, the number of protruded MDF per colon increased (p<0.01), and the percentage of DHG in a protruded MDF lesion decreased but that of AC increased remarkably. In conclusion, MDF may develop into cancer through the so-called 'de novo cancer' pathway. PMID- 22294267 TI - Addition of an indoleamine 2,3,-dioxygenase inhibitor to B cell-depletion therapy blocks autoreactive B cell activation and recurrence of arthritis in K/BxN mice. AB - OBJECTIVE: To define the role of indoleamine 2,3-dioxygenase (IDO) in driving pathogenic B cell responses that lead to arthritis and to determine if inhibitors of the IDO pathway can be used in conjunction with therapeutic B cell depletion to prevent the reemergence of autoantibodies and arthritis following reconstitution of the B cell repertoire. METHODS: Immunoglobulin-transgenic mice were treated with the IDO inhibitor 1-methyltryptophan (1-MT) and monitored for the extent of autoreactive B cell activation. Arthritic K/BxN mice were treated with B cell depletion alone or in combination with 1-MT. Mice were monitored for the presence of autoantibody-secreting cells, inflammatory cytokines, and joint inflammation. RESULTS: Treatment with 1-MT did not affect the initial activation or survival of autoreactive B cells, but it did inhibit their ability to differentiate into autoantibody-secreting cells. Treatment with anti-CD20 depleted the B cell repertoire and attenuated arthritis symptoms; however, the arthritis symptoms rapidly returned as B cells repopulated the repertoire. Administration of 1-MT prior to B cell repopulation prevented the production of autoantibodies and inflammatory cytokines and flare of arthritis symptoms. CONCLUSION: IDO activity is essential for the differentiation of autoreactive B cells into antibody-secreting cells, but it is not necessary for their initial stages of activation. Addition of 1-MT to therapeutic B cell depletion prevents the differentiation of autoantibody-secreting cells and the recurrence of autoimmune arthritis following reconstitution of the B cell repertoire. These data suggest that IDO inhibitors could be used in conjunction with B cell depletion as an effective cotherapeutic strategy in the treatment of rheumatoid arthritis. PMID- 22294268 TI - Virtual temporal bone dissection system: OSU virtual temporal bone system: development and testing. AB - OBJECTIVES/HYPOTHESIS: The objective of this project was to develop a virtual temporal bone dissection system that would provide an enhanced educational experience for the training of otologic surgeons. STUDY DESIGN: A randomized, controlled, multi-institutional, single-blinded validation study. METHODS: The project encompassed four areas of emphasis: structural data acquisition, integration of the system, dissemination of the system, and validation. RESULTS: Structural acquisition was performed on multiple imaging platforms. Integration achieved a cost-effective system. Dissemination was achieved on different levels including casual interest, downloading of software, and full involvement in development and validation studies. A validation study was performed at eight different training institutions across the country using a two-arm randomized trial where study subjects were randomized to a 2-week practice session using either the virtual temporal bone or standard cadaveric temporal bones. Eighty subjects were enrolled and randomized to one of the two treatment arms; 65 completed the study. There was no difference between the two groups using a blinded rating tool to assess performance after training. CONCLUSIONS: A virtual temporal bone dissection system has been developed and compared to cadaveric temporal bones for practice using a multicenter trial. There was no statistical difference between practice on the current simulator compared to practice on human cadaveric temporal bones. Further refinements in structural acquisition and interface design have been identified, which can be implemented prior to full incorporation into training programs and used for objective skills assessment. PMID- 22294269 TI - Human metapneumovirus (hMPV) in acute respiratory infection: a clinic-based study in Egypt. AB - OBJECTIVE: To estimate the prevalence of Human metapneumovirus (hPMV), its epidemiological and clinical features in infants and children with respiratory infections, attending outpatients' clinic of Mansoura University Children Hospital (MUCH). METHODS: After taking history, clinical examination and appropriate investigations, nasopharyngeal aspirates were collected from 600 infants and children with symptoms and signs of respiratory infections. Samples were examined by RT-PCR for hMPV. RESULTS: The overall prevalence of hMPV infection among studied patients was 8% (95% = 6.1-10.4). The rate was significantly higher among children aged 2-24 mo compared to other age groups (11.9% vs. 3.7% and 4.0% for 2-24, 25-60, 61-108 mo respectively). Also it was significantly higher among females than males (12.6% vs. 6.6%). Cough, wheezing, rhinorrhea, fever and chest wall retraction were the most frequent presentations (81.2%, 68.8%, 66.7%, 64.6% and 56.3%; respectively). Antibiotics, bronchodilators and oxygen administration were the most common treatments offered (60.4%, 31.2% and 27.1%; respectively). CONCLUSIONS: hMPV is an emerging cause of acute respiratory infection in Mansoura University Children Hospital (MUCH), and may have a significant clinical impact on infants and children and thus, must be considered in etiological diagnosis. PMID- 22294270 TI - Transient aplastic crisis in hereditary elliptocytosis. AB - Hereditary Elliptocytosis is a heterogeneous group of disorder with regard to clinical presentation, protein defects and mode of inheritance. Parvoviral induced transient aplastic crisis in the form of sudden onset anemia is said to be a rare manifestation of this hereditary hemolytic anemia. The authors describe a case of parvoviral induced transient aplastic crisis in a patient with hereditary elliptocytosis and review the pathogenic mechanisms of parvoviral hemolytic disease. PMID- 22294271 TI - Eventration of diaphragm with gastric duplication cysts: a rare association. AB - Eventration of diaphragm is defined as an abnormal and permanent elevation of the hemidiaphragm without defects. It may be congenital (muscular hypoplasia) or acquired (injury of the phrenic nerve). Diaphragmatic eventration has been reported alone or in association with other malformations. Here the authors are presenting a case of eventration of diaphragm with gastric duplication cysts because they could not find such association in the available English literature. PMID- 22294272 TI - Brain tumors in children--current therapies and newer directions. AB - Brain tumors are the second most common malignancy and the major cause of cancer related mortality in children. Though significant advances in neuroimaging, neurosurgery, radiation therapy and chemotherapy have evolved over the years, overall survival rate remains less than 75%. Malignant gliomas, high risk medulloblastoma with recurrence and infant brain tumors continue to be a major cause of therapeutic frustration. Even today diffuse pontine gliomas are universally fatal. Though tumors like low grade glioma have an overall excellent survival, recurrences and progression in eloquent areas pose therapeutic challenges. As research continues to unravel the biology including key molecules and signaling pathways responsible for the oncogenesis of different childhood brain tumors, novel targeted therapies are profiled. Identification of major targets like the Epidermal Growth factor Receptor (EGFR), Platelet Derived Growth Factor Receptor (PDGFR), Vascular Endothelial Growth factor (VEGF) and key signaling pathways like the MAPK and PI3K/Akt/mTOR has enabled us over the recent years to better understand tumor behavior and design tailored therapy. These efforts have improved overall survival of children with brain tumors. This review article discusses the current status of common brain tumors in children and the newer therapeutic approaches. PMID- 22294273 TI - Unsynchronized Nasal Intermittent Positive Pressure Ventilation vs. head box oxygen for preventing extubation failure. PMID- 22294274 TI - Multifocal nephrogenic adenoma - a mimicker of malignancy. AB - The authors report a multifocal nephrogenic adenoma of urinary bladder in an 11-y old girl. Nephrogenic adenomas occur almost exclusively in the urinary bladder in children and are rarely multifocal. Less than 30 cases of nephrogenic adenomas have been reported in children and very few of these are multifocal. This report aims at drawing attention to this rare entity in children. PMID- 22294275 TI - Association study between TRIM26 polymorphisms and risk of aspirin-exacerbated respiratory disease. AB - Aspirin-exacerbated respiratory disease (AERD) is a clinical syndrome that is characterized by nasal polyposis, general symptoms of asthma and sensitive response to non-steroidal anti-inflammatory drugs (NSAIDs). Although the exact function of tripartite motif-containing 26 (TRIM26) still remains unknown, the gene functions in the immune response. Thus, we hypothesized that TRIM26 polymorphisms may affect aspirin-induced bronchospasm and explored whether the gene can be a marker for diagnosis of AERD. To investigate our hypothesis that TRIM26 may serve as a genetic marker for diagnosis of AERD, this study focused on demonstrating the associations between single nucleotide polymorphisms (SNPs) of the TRIM26 gene and AERD. We genotyped 18 polymorphisms of TRIM26 in a total of 189 asthmatics and examined their associations with the risk of AERD. We performed logistic analysis for obtaining P-values and regression analysis for demonstrating an association between the phenotype with FEV1 and the genotype. We observed no associations between polymorphisms in TRIM26 and the risk of AERD in both logistic and regression analyses. Although our results reveal a lack of association, the suggested functional role of TRIM26 makes it a putative candidate gene for AERD. Thus, replications in other populations using larger samples may provide valuable information for AERD etiology. PMID- 22294276 TI - On similarity of hydrogen-bonded networks in liquid formamide and water as revealed in the static dielectric studies. AB - The paper presents the experimental verification of the result obtained with the molecular dynamics simulation which revealed the differences in the topology of the hydrogen-bonded networks in liquid formamide and water, namely, the differences in their intermolecular cyclization process (I. Bako, et al. J. Chem. Phys. 2010, 132, 014506). It is shown in our paper that the difference in the (simulated) size distribution of the hydrogen-bonded molecular rings in water (a relatively sharp maximum at about 6 molecules) and formamide (a broad maximum at about 11 molecules) strongly manifests itself in the experimental values of the Kirkwood correlation factor of the compounds. A much larger number of molecules included in the cyclic species (of more or less compensated dipole moment) leads to significant decrease of the Kirkwood correlation factor of formamide in comparison to that of water. Besides, as a consequence of an enhancement in formation of the cyclic multimers of formamide, one observes an essential reduction of the orientational entropy increment of that liquid, in comparison to the entropy effect related to liquid amides where the chain multimers are formed. PMID- 22294277 TI - Time-dependent changes in non-COX-1-dependent platelet function with daily aspirin therapy. AB - To develop an integrated metric of non-COX-1-dependent platelet function (NCDPF) to measure the temporal response to aspirin in healthy volunteers and diabetics. NCDPF on aspirin demonstrates wide variability, despite suppression of COX-1. Although a variety of NCDPF assays are available, no standard exists and their reproducibility is not established. We administered 325 mg/day aspirin to two cohorts of volunteers (HV1, n = 52, and HV2, n = 96) and diabetics (DM, n = 74) and measured NCDPF using epinephrine, collagen, and ADP aggregometry and PFA100 (collagen/epi) before (Pre), after one dose (Post), and after several weeks (Final). COX-1 activity was assessed with arachidonic acid aggregometry (AAA). The primary outcome of the study, the platelet function score (PFS), was derived from a principal components analysis of NCDPF measures. The PFS strongly correlated with each measure of NCDPF in each cohort. After 2 or 4 weeks of daily aspirin the Final PFS strongly correlated (r > 0.7, P < 0.0001) and was higher (P < 0.01) than the Post PFS. The magnitude and direction of the change in PFS (Final-Post) in an individual subject was moderately inversely proportional to the Post PFS in HV1 (r = -0.45), HV2 (r = -0.54), DM (r = -0.68), P < 0.0001 for all. AAA remained suppressed during aspirin therapy. The PFS summarizes multiple measures of NCDPF. Despite suppression of COX-1 activity, NCDPF during aspirin therapy is predictably dynamic: those with heightened NCDPF continue to decline whereas those with low/normal NCDPF return to pre-aspirin levels over time. PMID- 22294278 TI - Augmentation of transgenic expression by ultrasound-mediated liposome microbubble destruction. AB - Non-invasive, efficient and tissue-specific transgenic technologies could be valuable in gene therapy. Although non-viral carriers may be safer and cheaper, they have a much lower transfection efficiency than viral gene carriers. The present study was designed to test the transgenic expression and safety of red fluorescent protein (RFP) in HeLa cells in vitro and in transplanted tumors of nude mice in vivo under ultrasound-mediated liposome microbubble destruction (UMLMD) conditions. Plasmids containing RFP were gently mixed with liposome microbubbles (LMs). The mixture was added to HeLa cells or injected into BALB/c mice by the tail vein under various ultrasound exposure and LM parameters, and then the transfection efficiencies were examined. The results in vivo and in vitro demonstrated that, following a comparison of the plasmid group, the ultrasound + plasmid group and the LM + plasmid group, UMLMD significantly increased the transgenic expression (P<0.01) without causing any apparent detrimental effect. From the study, we concluded that UMLMD could be a non invasive, effective and promising non-viral technique for gene therapy and transgenic research. PMID- 22294279 TI - Dose dependence and temporal evolution of the T1 relaxation time and MRI contrast in the rat brain after subcutaneous injection of manganese chloride. AB - Divalent manganese ion (Mn(2+)) is a widely used T(1) contrast agent in manganese enhanced MRI studies to visualize functional neural tracts and anatomy in the brain in vivo. In animal studies, Mn(2+) is administered at a dose that will maximize the contrast, while minimizing its toxic effects. In rodents, systemic administration of Mn(2+) via intravenous injection has been shown to create unique MRI contrast in the brain at a maximum dose of 175 mg kg(-1). However, intravenous administration of Mn(2+) results in faster bioelimination of excess Mn(2+) from the plasma due to a steep concentration gradient between plasma and bile. By contrast, following subcutaneous injection (LD(50) value = 320 mg kg( 1)), Mn(2+) is released slowly into the bloodstream, thus avoiding immediate hepatic elimination resulting in prolonged accumulation of Mn(2+) in the brain via the choroid plexus than that obtained via intravenous administration. The goal of this study was to investigate MRI dose response of Mn(2+) in rat brain following subcutaneous administration of Mn(2+). Dose dependence and temporal dynamics of Mn(2+) after subcutaneous injection can prove useful for longitudinal in vivo studies that require brain enhancement to persist for a long period of time to visualize neuroarchitecture like in neurodegenerative disease studies. PMID- 22294280 TI - Endocytic collagen degradation: a novel mechanism involved in protection against liver fibrosis. AB - Fibrosis of the liver and its end-stage, cirrhosis, represent major health problems worldwide. In these fibrotic conditions, activated fibroblasts and hepatic stellate cells display a net deposition of collagen. This collagen deposition is a major factor leading to liver dysfunction, thus making it crucially important to understand both the collagen synthesis and turnover mechanisms in this condition. Here we show that the endocytic collagen receptor, uPARAP/Endo180, is a major determinant in governing the balance between collagen deposition and degradation. Cirrhotic human livers displayed a marked up regulation of uPARAP/Endo180 in activated fibroblasts and hepatic stellate cells located close to the collagen deposits. In a hepatic stellate cell line, uPARAP/Endo180 was shown to be active in, and required for, the uptake and intracellular degradation of collagen. To evaluate the functional importance of this collagen receptor in vivo, liver fibrosis was induced in uPARAP/Endo180 deficient mice and littermate wild-type mice by chronic CCl(4) administration. A strong up-regulation of uPARAP/Endo180 was observed in wild-type mice, and a quantitative comparison of collagen deposits in the two groups of mice clearly revealed a fibrosis protective role of uPARAP/Endo180. This effect appeared to directly reflect the activity of the collagen receptor, since no compensatory events were noted when comparing the mRNA expression profiles of the two groups of mice in an array system focused on matrix-degrading components. This function of uPARAP/Endo180 defines a novel role of intracellular collagen turnover in fibrosis protection. PMID- 22294281 TI - Lung function decline and blood lead among residents nearby to industrial complex. AB - PURPOSE: This study was to ascertain the risk factors of pulmonary function decline (forced expiratory volume in 1 s [FEV(1)], forced vital capacity [FVC]) among those exposed to lead in the vicinity of industrial complex. METHODS: In total, 263 men and women, aged over 30, were recruited from two cities during a 2 year follow-up. Spirometry testing was conducted first at baseline and then after 2-years of follow-up. The change in FVC and FEV(1) during the study period was analyzed according to blood lead (BPb), urinary cotinine, and 1-hydroxypyrene, after controlling for sex, height, baseline FVC or FEV(1), and airway hyperresponsiveness. RESULTS: With increase in age, both FEV(1) and FVC declined. More marked decline in FVC was noted for men than for women (p < 0.05), while the decline in FEV(1) was not. Biological variables, especially height (p < 0.05) and pulmonary status (p < 0.0001), were associated with the decline in both FEV(1) and FVC. Even after controlling these other variables, blood lead level was also significantly associated with the decline of FVC. CONCLUSIONS: Even though the decline in FEV(1) and FVC with aging was within a normal range, people with smaller height were more vulnerable to the decline of both FEV(1) and FVC and especially higher level of BPb was accompanied with larger decline of FVC. Oxidative stress in relation to lead accumulation in adult may contribute to rapid aging of pulmonary function. PMID- 22294282 TI - Estimations of the increasing prevalence and plateau prevalence of chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy. AB - BACKGROUND: The annual incidence of chronic myeloid leukemia (CML) in the United States is approximately 4800 cases. With the success of tyrosine kinase inhibitor (TKI) therapy, the all-cause annual mortality rate was reduced to 2%. Therefore, the prevalence of CML is increasing over time. Estimating the CML prevalence and plateau prevalence is important in the implementation of health care strategies and future therapeutic trials. The objective of this report was to estimate the increasing prevalence and plateau prevalence of CML in future years. METHODS: The prevalence of CML was estimated based on several parameters: the annual mortality rate on TKI therapy compared with a age-matched, normal population; the incidence of CML; the anticipated population growth in the United States; and aging of the population. RESULTS: On the basis of these calculations, the mortality ratio of patients with CML compared with an age-matched normal population was approximately 1.53. The estimated prevalence of CML is approximately 70,000 in 2010, 112,000 in 2020, 144,000 in 2030, 167,000 in 2040, and 181,000 in 2050, when it will reach a near plateau prevalence. CONCLUSIONS: The current results indicated that the prevalence of CML will continue to increase to reach a near plateau prevalence 35 times the annual incidence. These estimates should be considered in health care policies and in the design of future studies in CML. PMID- 22294283 TI - Isoquinoline alkaloids from Tinospora cordifolia inhibit rat lens aldose reductase. AB - The inhibitory activity of Tinospora cordifolia stem-derived alkaloids was evaluated against lens aldose reductase (AR) isolated from male Wistar rats. Anticataract potential of the alkaloids of T. cordifolia was evaluated in vitro in rat lenses, considering the activity of normal rat lenses as 100%. The biologically active constituents of T. cordifolia extract were characterized as the isoquinoline alkaloids, jatrorrhizine, palmatine and magnoflorine, by spectral analysis. The inhibitory effects varied with all chemicals and concentrations used. The inhibitory concentration (IC50) values of jatrorrhizine, palmatine and magnoflorine are 3.23, 3.45 and 1.25 ug/mL respectively. The concentration of maximum activity was selected for its effect on galactose induced polyol accumulation in vitro. The percentage inhibition of galactose induced polyol accumulation was 62.6, 58.8 and 27.7% in the presence of jatrorrhizine, palmatine and magnoflorine, respectively. Magnoflorine may be useful as lead compounds and new agents for AR inhibition. PMID- 22294284 TI - [Tuberculosis infection control--recommendations of the DZK]. AB - The epidemiological situation of tuberculosis (TB) in Germany has improved considerably during the past few years. However, those in unprotected contact with infectious tuberculosis patients frequently and/or over longer periods of time and/or intensively continue to have a higher risk for TB infection. Rapid diagnosis, prompt initiation of effective treatment, and adequate infection control measures are of particular importance to prevent infection. The present recommendations depict the essentials of infection control as well as specific measures in the hospital (isolation, criteria for its duration and technical requirements, types of respiratory protection, disinfection measures, waste disposal). The specific requirements for outpatients (medical practice), at home, for ambulance services, and in congregate settings, including prisons, are also addressed. Compared with the previous recommendations the pattern of respiratory protection measures has been simplified. As a rule, hospital staff and those visiting infectious tuberculosis patients are advised to wear respiratory protection that satisfies the criteria of FFP2-masks (DIN EN 149), while patients should wear mouth-nose protectors (surgical masks) in the presence of others and outside the isolation room. A detailed depiction of criteria for isolation and its duration in smear positive and only culturally confirmed pulmonary tuberculosis has been added. PMID- 22294285 TI - Synthesis of (+)-L-733,060, (+)-CP-99,994 and (2S,3R)-3-hydroxypipecolic acid: application of an organocatalytic direct vinylogous aldol reaction. AB - The gamma-butenolide obtained from an organocatalyzed, direct vinylogous aldol reaction of gamma-crotonolactone and benzaldehyde serves as the key starting material in the expedient synthesis of a 3-hydroxy-2-phenyl piperidine intermediate which is converted to the target 2,3-disubstituted piperidines. PMID- 22294286 TI - Differential staining of gamma synuclein in poorly differentiated compared to highly differentiated colon cancer cells. AB - Synuclein alpha, beta and gamma are proteins usually found in neurodegenerative diseases. However, interestingly synucleins are expressed in cancer cells of several organs including ovary, mammary gland and colon. By immunocytochemistry using specific antibodies to gamma synuclein (SNCG), we examined the distribution of this protein in poorly differentiated, compared to highly differentiated colon cancer cells. In poorly differentiated cancer cells tumors were very frequently stained intensely with antibodies to SNGG, suggesting high expression of this protein. In contrast, in highly differentiated cells, there was no labeling. Labeled cells could be found only at the edges or in between the lobules of the differentiated tumor cells. However, in moderately differentiated tumors, a weak cytoplasmic staining of SNCG was evident. Interestingly in cancer patients (stage II-IV) both poorly and highly differentiated tumor cells were often present in the same patient. Labeled cancer cells with SNCG were evident also in lymph nodes, around the wall of blood vessels and in fat tissue, where only poorly differentiated cancer cells were exclusively present. Since cancer cells with poor differentiation are believed to be aggressive with metastases formation it is suggested that SNCG can serve as a marker for the potential of the tumor cell for the rapid spreading and metastazing of the non-differentiated tumors. PMID- 22294287 TI - Do you know what I mean? Laypeople and experts' concepts of cognition. AB - Patients' cognitive complaints and subsequent performance on neuropsychological tests often fail to relate. This could, in part, be caused by a Babylonic incongruence between laypeople's and experts' use of cognition words or "jargon." The present study examined the concurrency of experts and laypeople for 18 neuropsychological tests in the cognitive domains "language," "memory," "attention/concentration," "perception," and "thinking" (executive functioning). This was done by correlating the classifications of the laypeople and experts for individual tests and within each domain. A high domain concurrency was found, indicated by domain correlations of the classifications between laypeople and experts ranging from r(s)=.79 to .92, with exception of the domain "attention" (r(s)=.32). Importantly, with respect to the classification of each individual test in a cognitive domain, large variations in correlations were found, ranging from r(s)=.30 up to r(s)=1.0. These results indicate that there is agreement between the concepts laypeople use and the theory-based concepts of the experts. Our study also offers valuable insight for the clinical practice: tests with a high correlation should be used to aid the clarity of communication in the clinical practice, for instance when giving feedback on performance. PMID- 22294288 TI - Safety analysis of percutaneous dilational tracheostomies with bronchoscopy in the obese patient. AB - OBJECTIVES/HYPOTHESIS: Since originally described in 1985 by Ciaglia, percutaneous dilational tracheostomy (PDT) has grown in popularity, and today is widely used for critically ill patients requiring long-term mechanical ventilation. Since the inception of PDT, obesity has been considered a relative contraindication to its use. The purpose of this study is to evaluate the risks of PDT in obese patients. STUDY DESIGN: Retrospective review. METHODS: A retrospective review was performed of prospectively collected data from 426 patients who underwent PDT at a single teaching institution from July 2003 to October 2009. The groups were separated into those who had a body mass index (BMI) of <30 or >=30 kg/m(2) . The following variables were collected: blood loss at the time of procedure, difficulty in tracheotomy dilation and/or tracheostomy placement, presence of tracheal ring breaks, any bleeding episodes requiring treatment by surgery or blood transfusion, pre- and postprocedure pneumonia, and stoma infection requiring antibiotics. All tracheostomies were placed using the Ciaglia Blue Rhino Introducer Kit (Cook Medical Inc., Bloomington, IN). Statistical analysis was performed with nonparametric statistics using chi(2) testing with P < .05 as significant. RESULTS: No statistically significant difference was found between the obese and nonobese groups for any of the variables studied. Similar results were found when BMI of 40 was used for grouping. CONCLUSIONS: PDT can be performed safely in obese patients. There were no statistically significant differences in measured variables found between the two study groups. This study supports the use of intensive care unit bedside PDT in the obese population. PMID- 22294289 TI - Prevalence of regurgitation and reingestion in orangutans housed in North American zoos and an examination of factors influencing its occurrence in a single group of Bornean orangutans. AB - Very little research has explored regurgitation and reingestion (R/R) in orangutans. We first aimed to determine the prevalence of R/R in the North American zoo population through a survey of accredited institutions. We report the prevalence of R/R in orangutans >4 years of age as 35% with some sex and species differences. Additionally, survey respondents reported fruit and sweet foods as the most common triggers of R/R. We also explored rates of R/R in a single group of Bornean orangutans at Cleveland Metroparks Zoo. We examined the relationship between R/R and feeding schedule and opportunistically observed rates of R/R with and without the presence of browse and sweet foods. We found evidence that R/R is associated with feeding time and that the presence of browse significantly increased the amount of time that animals spent feeding. There was a trend toward decreased R/R when browse was available. We also observed higher rates of R/R when sweet foods were available and we propose that this may have mitigated some of the beneficial effects of browse. We suggest that future studies look further at nutritional influences on R/R behavior. PMID- 22294290 TI - New evidence for the role of proteasome inhibitors in systemic lupus erythematosus: comment on the article by Ichikawa et al. PMID- 22294292 TI - Mechanical efficiency and force-time curve variation during repetitive jumping in trained and untrained jumpers. AB - Mechanical efficiency (ME), the ratio between work performed and energy expenditure, is a useful criterion in determining the roles of stored elastic energy and chemically deduced energy contributing to concentric performance in stretch-shortening cycle movements. Increased force production during the eccentric phase has been shown to relate to optimal muscle-tendon unit (MTU) length change and thus optimization of usage of stored elastic energy. This phenomenon, as previously reported, is reflected by higher jump heights and ME. The purpose of this investigation was to determine if ME may be different between trained and untrained jumpers and thus be accounted for by variation in force production in the eccentric phase as a reflection of usage of stored elastic energy during various jump types. This investigation involved 9 trained (age 20.7 +/- 3.2 years, height 178.6 +/- 5.3 cm, body mass 79.0 +/- 5.5 kg) and 7 untrained (age 21.43 +/- 2.37 years, height 176.17 +/- 10.89 cm, body mass 78.8 +/- 12.5 kg) male jumpers. Trained subjects were Division I track and field athletes who compete in the horizontal or vertical jumping or running events. Force-time and displacement-time curves were obtained during jumping to determine jump height and to calculate work performed and to observe possible differences in force production in the eccentric phase. Respiratory gases with a metabolic cart were obtained during jumping to calculate energy expenditure. ME was calculated as the ratio between work performed and energy expenditure. The subjects completed four sessions involving 20 repetitions of countermovement jumps (CMJ) and drop jumps from 40 cm (DJ40), 60 cm (DJ60) and 80 cm (DJ80). The trained jumpers jumped significantly higher in the CMJ, DJ40, DJ60 and DJ80 conditions than their untrained counterparts (p <= 0.05). ME was significantly higher in the trained in comparison to the untrained jumpers during DJ40. The amount of negative work during all jump types was significantly greater in the trained jumpers. There was a significant correlation between negative work and ME in the trained jumpers (r = 0.82) but not in the untrained jumpers (r = 0.54). The present study indicates that trained jumpers jump higher and have greater ME, possibly as a result of increased for production in the eccentric phase as a reflection of optimal MTU length change and thus increased usage of storage of elastic energy. PMID- 22294293 TI - Validity and reliability of the Horiba C-122 compact sodium analyzer in sweat samples of athletes. AB - Accurate sodium replacement during prolonged exercise is possible when sweat rate and sweat sodium content are directly measured. Few athletes have access to sweat sodium content measurement, as the equipment needed to perform such analyzes is costly, laboratory-based or requires technical skills. Using 70 sweat samples collected in 24 athletes from 3 anatomical sites, this study determined the reliability [single-trial and inter-day (7 samples over 3 days)] and validity (instrument error) of a pocket-sized, easy-to-use and low cost sodium analyzer (Horiba C-122, Kyoto, Japan) against reference values of an ion chromatograph, the 883 Basic IC plus (Metrohm AG, Herisau, Switzerland). The Horiba C-122 showed high single-trial reliability with an intraclass correlation coefficient (ICC) of 0.997, a typical error of measurement (EM) of 1.77 mmol/L and a coefficient of variation (CV) of 3.73%. As expected, the reliability of the 883 Basic IC plus was superior to that of the Horiba C-122 (ICC: 0.999; typical EM: 0.70 mmol/L; CV: 1.52%). The Horiba's C-122 inter-day reliability was high (ICC: 1.00; typical EM: 0.35 mmol/L). An ICC of 0.975 indicates there was a strong relationship between results provided by both analyzers. Compared with reference values, the Horiba C-122 demonstrated a mean bias of 1.71 mmol/L, a pure EM of 7.52 mmol/L and 68% limits of agreement ranging from -5.81 to 9.23 mmol/L. We propose that the Horiba C-122 is sufficiently reliable to be used under field conditions where some degree of imprecision is acceptable, but not for research purposes where high accuracy is required. PMID- 22294294 TI - Cancer mortality-to-incidence ratios in Georgia: describing racial cancer disparities and potential geographic determinants. AB - BACKGROUND: The objective of this study was to evaluate racial cancer disparities in Georgia by calculating and comparing mortality-to-incidence ratios (MIRs) by health district and in relation to geographic factors. METHODS: Data sources included cancer incidence (Georgia Comprehensive Cancer Registry), cancer mortality (Georgia Vital Records), and health factor (County Health Rankings) data. Age-adjusted incidence and mortality rates were calculated by cancer site (all sites combined, lung, colorectal, prostate, breast, oral, and cervical) for 2003-2007. MIRs and 95% confidence intervals were calculated overall and by district for each cancer site, race, and sex. MIRs were mapped by district and compared with geographic health factors. RESULTS: In total, 186,419 incident cases and 71,533 deaths were identified. Blacks had higher MIRs than whites for every cancer site evaluated, and especially large differentials were observed for prostate, cervical, and oral cancer in men. Large geographic disparities were detected, with larger MIRs, chiefly among blacks, in Georgia compared with national data. The highest MIRs were detected in west and east central Georgia, and the lowest MIRs were detected in and around Atlanta. Districts with better health behavior, clinical care, and social/economic factors had lower MIRs, especially among whites. CONCLUSIONS: More fatal cancers, particularly prostate, cervical, and oral cancer in men were detected among blacks, especially in central Georgia, where health behavior and social/economic factors were worse. MIRs are an efficient indicator of survival and provide insight into racial cancer disparities. Additional examination of geographic determinants of cancer fatality in Georgia as indicated by MIRs is warranted. PMID- 22294295 TI - Vibration-synchronized magnetic resonance imaging for the detection of myocardial elasticity changes. AB - Vibration synchronized magnetic resonance imaging of harmonically oscillating tissue interfaces is proposed for cardiac magnetic resonance elastography. The new approach exploits cardiac triggered cine imaging synchronized with extrinsic harmonic stimulation (f = 22.83 Hz) to display oscillatory tissue deformations in magnitude images. Oscillations are analyzed by intensity threshold-based image processing to track wave amplitude variations over the cardiac cycle. In agreement to literature data, results in 10 volunteers showed that endocardial wave amplitudes during systole (0.13 +/- 0.07 mm) were significantly lower than during diastole (0.34 +/- 0.14 mm, P < 0.001). Wave amplitudes were found to decrease 117 +/- 40 ms before myocardial contraction and to increase 75 +/- 31 ms before myocardial relaxation. Vibration synchronized magnetic resonance imaging improves the temporal resolution of magnetic resonance elastography as it overcomes the use of extra motion encoding gradients, is less sensitive to susceptibility artifacts, and does not suffer from dynamic range constraints frequently encountered in phase-based magnetic resonance elastography. PMID- 22294296 TI - Effects of the pro-inflammatory milieu on the dedifferentiation of cultured fibroblast-like synoviocytes. AB - The aim of this study was to determine whether the inflammatory milieu and/or hypoxia induces the dedifferentiation of synovial cells into mesenchymal stem like cells, which may contribute to the tumor-like growth of synovial cells. Expression of mesenchymal stem cell markers (CD24, CD44, CD90, CD106, CD146 and Stro-1) was compared among cultured fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) or osteoarthritis (OA), bone marrow mesenchymal stem cells (BM MSCs) and normal dermal fibroblasts. After the cells were stimulated with pro-inflammatory cytokines for 3 days under hypoxia or normoxia, the stem cell markers were analyzed by FACS. CD44 and CD90 were expressed constitutively in all four cell types. Only the BM MSCs strongly expressed CD146. The expression of stem cell markers was similar between FLSs from RA and those from OA patients. In addition, the expression levels in FLSs were similar to those in normal dermal fibroblasts. The stimulation of FLSs and dermal fibroblasts with IL-1beta or a mixture of cytokines under hypoxia did not induce a marked change in the expression of stem cell markers. These results indirectly suggest that the pro-inflammatory milieu may be not sufficient to induce the dedifferentiation of FLSs in arthritic joints. PMID- 22294297 TI - Non-junctional human desmoglein 3 acts as an upstream regulator of Src in E cadherin adhesion, a pathway possibly involved in the pathogenesis of pemphigus vulgaris. AB - E-cadherin, a classical cadherin, is an adhesion receptor in adherens junctions and has important functions in cell-cell adhesion and cell signalling. Recently we reported that a desmosomal cadherin, desmoglein 3 (Dsg3), an autoantigen in pemphigus vulgaris (PV), associates with E-cadherin and activates Src, which results in tyrosine phosphorylation of adherens junction proteins. However, the nature of such an interaction and its role in cell-cell adhesion remain unclear. In this report, we provide direct evidence that it is the detergent-soluble, non desmosomal Dsg3 that regulates the activity of Src and its association with E cadherin in adherens junction formation. Modulation of Dsg3 levels, either by Dsg3 silencing or over-expression, alters Src activity and its association with E cadherin. Dsg3 silencing caused retardation of calcium-induced E-cadherin junction assembly and a reduction of desmosomal protein expression. Furthermore, we provide evidence that this signalling pathway is involved, at least in part, in the pathophysiology of pemphigus. Along with the reduced expression of Dsg3, loss and disruption of E-cadherin and a concomitant decreased pSrc signalling was identified in the basal keratinocytes surrounding the blisters in PV. These findings suggest a novel function for Dsg3 in the control of E-cadherin-Src signalling and cell-cell adhesion. PMID- 22294298 TI - Bioactivity of sour cherry cultivars grown in Denmark. AB - Thirty four varieties of sour cherries (Prunus cerasus) were investigated for their total antioxidant activity, Caco-2 cancer cell proliferation inhibitory activity and effect on prostaglandin E2 (PGE2) production. Total phenolic content, oxygen radical absorbance capacity (ORAC) and cancer cell proliferation inhibitory activity of sour cherries were closely correlated but not PGE2 production. The cultivars 'Birgitte * Bottermo', 'Fanal' and 'Tiki' were the three cultivars with the highest ORAC values (180, 147 and 133 umol TE/g, respectively) and inhibition against Caco-2 cancer cell proliferation (74%, 79% and 73%, respectively). 'Stevnsbaer Birgitte' (22%) and 'Stevnsbaer Viki' (22%) inhibited PGE2 production with a similar potency as the positive controls indomethacin and NS-398. Significant differences between cultivars in all bioactivity experiments indicated that selection of cultivars is important to obtain sour cherries with better potential health promoting effects. PMID- 22294299 TI - [Shift work]. PMID- 22294301 TI - [Supervised exercise training in patients with pulmonary arterial hypertension - analyses of the effectiveness and safety]. AB - Both in today's scientific research and in clinical practice, there exists a need to address the uncertainty concerning the effectiveness and safety of cardiopulmonary exercise training (CPET) in patients with pulmonary arterial hypertension (PAH). It is commonly believed that CPET may be dangerous for patients with PAH, because increasing pressure on the pulmonary arteries may worsen right-sided heart failure. Recently, the first clinical trials on exercise training in patients with pulmonary hypertension reported promising results. Extension of the walking distance at the 6-minute walk test improved quality of life, endurance capacity and a reduction in symptoms were observed after CPET. Furthermore, CPET was well tolerated by the patients in five clinical trials. In conclusion, it may be postulated that CPET is an effective therapy in patients with PAH and was tendentially well tolerated by the patients. PMID- 22294302 TI - [Identification of patients at risk for adverse outcomes in emergency department: which screening tools?]. AB - Taking care of elderly patients is difficult in emergency settings. Such patients are at risk of becoming non autonomous or to be rehospitalized. An individualized evaluation makes it possible to decrease this risk but is time consuming, which represents a problem when it is crucial to maintain the flux of patients. Several tools allowing the tracking down of patients at risk have been developed with the aim to identify those who are likely to benefit from a management and those who could, on the opposite, be discharged without performing investigations. The aim of this review is to depict the different tools available to track down patients at risk and to evaluate their efficacy and usefulness in an emergency setting. PMID- 22294303 TI - [Gait changes and fall risk]. AB - Walking is a complex motor task generally performed automatically by older adults. Falls with or without serious consequences such as fractures or fear of falling can be the result. Gait analysis shows that even minor stride-to-stride variations increase the risk for falls. These gait changes are often too small to be detected during normal walking alone, but rather appear in combination with an additional task, the so-called dual tasking. Irregular gait is not an inevitability of older age, but can be improved by targeted interventions. PMID- 22294304 TI - [Assisted suicide - medical, legal, and ethical aspects]. AB - Unlike in most European countries, assisted suicide is not illegal in Switzerland. The number of assisted suicides procured by right-to-die organisations such as Exit or Dignitas has sharply increased in the last twenty years. Central part of the doctor's involvement is the prescription of a lethal dose of sodium pentobarbital. In doing so, the doctor has to apply to the rules of medical due care. A proper examination of the patient is required, who must be informed about his diagnosis, about the expected prognosis, and about different treatment options. Verification of the patient's decisional capacity is crucial. In general, a staff member of the organisation but not the doctor is present during suicide. Following death, the assisted suicide has to be reported to the police as an extraordinary death case. PMID- 22294305 TI - [Diagnosis in suspected lower respiratory infection and therapy resistance]. PMID- 22294306 TI - [Herbal drugs mimicking primary biliary cirrhosis]. AB - A woman, who consumed the recommended daily doses of Relaxane(r) and Hova(r) over several months was found to have elevated liver enzymes. A liver biopsy showed histologic changes consistent with primary biliary cirrhosis. After stopping treatment with Relaxane(r) and Hova(r) we observed a decline of the increased liver enzymes to normal levels two months later. A second biopsy of the liver three months later showed a clear decline of the initial histologic changes. PMID- 22294307 TI - [Stratified management of patients with lumbar backache in primary care]. PMID- 22294308 TI - [Individual education is superior to group education in suboptimally managed type 2 diabetes]. PMID- 22294310 TI - [CME ultrasound diagnosis 44. Methadone substitution therapy and chronic hepatitis C]. PMID- 22294313 TI - Pretravel preparation and travel-related morbidity in patients with inflammatory bowel disease. AB - BACKGROUND: There are no published data on health preparation and travel-related morbidity in patients with inflammatory bowel disease (IBD). METHODS: A retrospective web-based questionnaire study on past travel experiences with more detailed questions concerning the most recent journey. Participants were recruited from the IBD outpatient clinic and via the website of the Dutch patient organization. RESULTS: In all, 277 patients who had traveled abroad during the past 5 years (172 Crohn's disease, 105 ulcerative colitis) filled out the questionnaire. The majority (62%) answered that IBD limited their choice of travel destinations. Forty-three percent traveled to resource-limited destinations and 76% thereof obtained pretravel advice. Only 48% were prescribed an antibiotic for self-treatment in case of infectious diarrhea, and 23% were not protected against hepatitis A. Fecal urgency and incontinence were the main IBD related inconveniences. Thirty-two percent reported a new episode of diarrhea and 28% thereof attributed it to an enteric infection. In total, 15/277 (5%) consulted a foreign physician, of whom five were admitted to hospital. Fifty-four (19%) had a self-reported exacerbation of IBD within 2 months following travel and 24% thereof attributed it to the recent travel. The Mantel-Haenszel odds ratio for an exacerbation within a 2-month period after travel was 1.1 (95% confidence interval [CI] 0.7-1.8) when the number of self-reported exacerbations in a 5-year period was used as reference and 1.5 (95% CI 0.9-2.6) when the year 2008 was used as reference. CONCLUSIONS: Pretravel advice for IBD patients was often deficient. There was a considerable amount of travel-related morbidity and inconvenience. PMID- 22294314 TI - Volumetric changes of the anterolateral thigh free flap following adjuvant radiotherapy in total parotidectomy reconstruction. AB - OBJECTIVES/HYPOTHESIS: The aim of this study was to prospectively evaluate volume change in anterolateral thigh free flaps pre- and postradiotherapy and to compare computed tomography (CT) volumetric analysis with intraoperative water displacement calculation. STUDY DESIGN: Matched pair cohort study. METHODS: Thirteen patients with advanced carcinoma of the parotid gland underwent anterolateral thigh free flap reconstruction following total parotidectomy resections and neck dissection. Before the initiation of external beam radiation, routine CT planning scans were done on all patients. A minimum of 6 months after surgery, a CT scan of the head and neck was carried out, and a detailed volumetric assessment was performed. RESULTS: The mean preradiotherapy flap volume was 94.3 mL, and the postradiotherapy volume was 84.8 mL. The mean volume reduction in all 13 patients was 8.12%. CONCLUSIONS: In this prospective study we observed an 8% volume loss in anterolateral thigh free flaps 6 months postradiotherapy. This loss of volume should be taken into account when reconstructing large defects of the face and lateral skull base. Intraoperative water displacement measurement is a useful adjunctive tool for shaping free tissue transfers that are to be used for volume replacement and soft-tissue fill in. PMID- 22294315 TI - Could the Cochin risk prediction score be applied in daily practice to predict pulmonary hypertension in systemic sclerosis? Comment on the article by Meune et al. PMID- 22294316 TI - Oxidant damage in Kashin-Beck disease and a rat Kashin-Beck disease model by employing T-2 toxin treatment under selenium deficient conditions. AB - Kashin-Beck disease (KBD) is an endemic degenerative osteoarthropathy, but the mechanisms underlying its pathogenesis remains unclear. This study compares antioxidant capacity and lipid peroxidation using a novel model, in which rats were administered a selenium-deficient diet for 4 weeks prior to their exposure to T-2 toxin for 4 weeks. Changes in cell morphology and empty chondrocyte lacunae indicative of cell death, as well as cartilage proteoglycan loss in the deep zone of articular cartilage of knee joints were observed in rats with selenium-deficient diet plus T-2 toxin treatment. These changes were similar to those observed previously in KBD. The levels of thiobarbituric acid reactive substances (TBARS), indicative of lipid peroxidation in serum and cartilage, were significantly increased in all experimental groups compared to the normal diet group, while the levels of antioxidants, measured as total antioxidant capacity (T-AOC), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidases (GPX), in serum and cartilage were significantly lower than that in the normal diet group. The mRNA expression of those antioxidants in cartilage tissue was significantly reduced by T-2 toxin alone or by selenium-deficient diet plus T-2 toxin treatment. These results indicate that increasing TBARS and decreasing antioxidants in serum and cartilage by T-2 toxin treatment with a selenium deficient nutritional status may alter oxidative stress in joint tissues and contribute to the pathological process of cartilage damage in KBD. PMID- 22294317 TI - The structural basis for substrate versatility of chloramphenicol acetyltransferase CATI. AB - Novel antibiotics are needed to overcome the challenge of continually evolving bacterial resistance. This has led to a renewed interest in mechanistic studies of once popular antibiotics like chloramphenicol (CAM). Chloramphenicol acetyltransferases (CATs) are enzymes that covalently modify CAM, rendering it inactive against its target, the ribosome, and thereby causing resistance to CAM. Of the three major types of CAT (CAT(I-III)), the CAM-specific CAT(III) has been studied extensively. Much less is known about another clinically important type, CAT(I). In addition to inactivating CAM and unlike CAT(III), CAT(I) confers resistance to a structurally distinct antibiotic, fusidic acid. The origin of the broader substrate specificity of CAT(I) has not been fully elucidated. To understand the substrate binding features of CAT(I), its crystal structures in the unbound (apo) and CAM-bound forms were determined. The analysis of these and previously determined CAT(I)-FA and CAT(III)-CAM structures revealed interactions responsible for CAT(I) binding to its substrates and clarified the broader substrate preference of CAT(I) compared to that of CAT(III). PMID- 22294318 TI - Equine cestodosis: a sero-epidemiological study of Anoplocephala perfoliata infection in Ethiopia. AB - A 12/13 kDa antigen, tapeworm ELISA test, developed for use in horses, was used to detect parasite-specific serum antibody, IgG(T), in the serum of donkeys. In a pilot study the 12/13 kDa antigen was tested and proved to detect the antibody, IgG(T), in donkey sera. Blood samples from 797 donkeys, naturally exposed to cestode infection, from four geographical localities were collected and sera were prepared and analysed. There was substantial serological evidence that donkeys were potentially infected with A. perfoliata. A range of ELISA OD values were obtained from the serological assay. Over 26% and 7.5% of the donkeys were moderately and highly infected, respectively, showing at least a 34% sero prevalence. The rest, 66.1%, were either with low infection intensity or negative for A. perfoliata infection. The risk of infections, both in sero-prevalence and intensity, as determined by ELISA optical density (OD), were highest in the highland areas of Ethiopia where pastures are low-lying and wet, and permanent pasture management is regularly practised. Sex, age and body condition of the donkeys had no significant effect either on prevalence of the infection or on the serum antibody level. These results indicate a risk of intestinal disorders, particularly, colic, associated with A. perfoliata infection in donkeys. PMID- 22294319 TI - Expectancies, socioeconomic status, and self-rated health: use of the simplified TOMCATS Questionnaire. AB - BACKGROUND: Coping has traditionally been measured with inventories containing many items meant to identify specific coping strategies. An alternative is to develop a shorter inventory that focusses on coping expectancies which may determine the extent to which an individual attempts to cope actively. PURPOSE: This paper explores the usefulness and validity of a simplified seven-item questionnaire (Theoretically Originated Measure of the Cognitive Activation Theory of Stress, TOMCATS) for response outcome expectancies defined either as positive ("coping"), negative ("hopelessness"), or none ("helplessness"). The definitions are based on the Cognitive Activation Theory of Stress (CATS; Ursin and Eriksen, Psychoneuroendocrinology, 29(5):567-92, 2004). The questionnaire was tested in two different samples. First, the questionnaire was compared with a traditional test of coping and then tested for validity in relation to socioeconomic differences in self-reported health. METHODS: The first study was a comparison of the brief TOMCATS with a short version of the Utrecht Coping List (UCL; Eriksen et al., Scand J Psychol, 38(3):175-82, 1997). Both questionnaires were tested in a population of 1,704 Norwegian municipality workers. The second study was a cross-sectional analysis of TOMCATS, subjective and objective socioeconomic status, and health in a representative sample of the Swedish working population in 2003-2005 (N = 11,441). RESULTS: In the first study, the coping item in the TOMCATS questionnaire showed an expected significant positive correlation with the UCL factors of instrumental mastery-oriented coping and negative correlations with passive and depressive scores. There were also the expected correlations for the helplessness and hopelessness scores, but there was no clear distinction between helplessness and hopelessness in the way they correlated with the UCL. In the second study, the coping item in TOMCATS and the three-item helplessness scores showed clear and monotonous gradients over a subjective socioeconomic status (SES) ladder. Positive response outcome expectancy ("coping") was related to high subjective SES and no expectancy ("helplessness") to low subjective SES. In a model including age and sex, TOMCATS scores explained more variance (r 2 = 0.16) in self-reported health than both subjective (r 2 = 0.08) and objective SES (r 2 = 0.02). CONCLUSION: The brief TOMCATS questionnaire showed acceptable and significant correlations with a traditional coping questionnaire and is sensitive enough to register systematic differences in response outcome expectancies across the socioeconomic ladder. The results furthermore confirm that psychological and learning factors contribute to the socioeconomic gradient in health. PMID- 22294320 TI - Providing audiological services to individuals with aphasia: considerations, preliminary recommendations, and a call for research. AB - PURPOSE: The populations most susceptible to hearing loss and to aphasia overlap substantially, creating a high likelihood that audiologists will be called on to assess and treat individuals with aphasia. There is, however, scarce research available to guide best practices for serving this population. METHOD: The available relevant literature is reviewed to summarize what is already known, providing basic information about aphasia and its potential impact on audiological diagnostic and intervention processes. CONCLUSION: Suggestions for managing aphasia in the clinical audiology setting are provided, and areas of needed research are identified so that services for individuals with aphasia can be optimized. PMID- 22294321 TI - A proteomic profile of washing fluid from the colorectal tract to search for potential biomarkers of colon cancer. AB - Washing fluid (WF) from the colon rectal tract after surgical resection might represent a first step in obtaining a mixture of proteins derived from the secretion of tumoral epithelial cells potentially involved in the pathological progression of tissue. In this study, we performed a proteomic analysis of colorectal WF to search for potential biomarkers of colon cancer. The outcome of this approach might open the possibility of using WF to screen for the precancerous and early stages of colorectal cancer (CRC). Samples of WFs were obtained during surgery from 35 patients submitted to colon resection for suspicious adenocarcinoma or carcinoma, while the respective controls were obtained by washing the healthy sections. WFs were immediately centrifuged, concentrated and trichloroacetic acid (TCA) was added to obtain protein pellets. After two-dimensional gel electrophoresis (2DE), the protein patterns of malignant samples were compared with respective normal samples. Forty-one protein spots were found to be differentially expressed exhibiting >=2 fold-change of mean value spot intensities. After mass spectrometry, these protein spots collapsed into 38 different proteins. Interestingly, 19 of the differentially expressed proteins identified in the study corresponded to those suggested as being potential biomarkers of CRC. In accordance with the literature, these proteins showed the same direction of change (up or down for all proteins). Our results suggest that WF has the potential of being a method for the exploration of clinical samples for biomarker and drug target discovery. PMID- 22294322 TI - The impact of insurance status on outcomes after surgery for spinal metastases. AB - BACKGROUND: Disparities based on insurance status in the American health care system are well established. However, to the authors' knowledge, this is the first study to evaluate variables that may explain differences based on payer type in the outcomes after surgery for spinal metastases. METHODS: Data from the Nationwide Inpatient Sample (2005-2008) were retrospectively extracted. Patients ages 18 to 64 years who underwent surgery for spinal metastases were included. Multivariate logistic regression was performed to calculate the adjusted odds of in-hospital death and the development of a complication for Medicaid recipients and for those without insurance compared with privately insured patients. All analyses were adjusted for differences in patient age, gender, primary tumor histology, socioeconomic status, hospital bed size, and hospital teaching status. RESULTS: A total of 2157 hospital admissions were evaluated. The adjusted odds of in-hospital death were significantly higher for Medicaid recipients (crude rate: 6.5%; odds ratio [OR], 1.79; 95% confidence interval [95% CI], 1.11-2.88 [P = .02]) and uninsured patients (crude rate: 7.7%; OR, 2.15; 95% CI, 1.04-4.46 [P = .04]) compared with privately insured patients (crude rate: 3.8%). Complication rates were also significantly higher for Medicaid recipients (OR, 1.34; 95% CI, 1.04-1.72 [P = .02]). However, after also adjusting for acuity of presentation, the odds of in-hospital death were not significantly different for Medicaid (OR, 1.38; 95% CI, 0.86-2.21 [P = .18]) or uninsured patients (OR, 1.86; 95% CI, 0.90 3.83 [P = .09]); in addition, complication rates did not appear to differ significantly. CONCLUSIONS: This nationwide study suggests that disparities based on insurance status for patients undergoing surgery for spinal metastases may be attributable to a higher acuity of presentation. PMID- 22294323 TI - The evaluation of surgical treatment for gastric cancer patients with noncurative resection. AB - PURPOSE: This study aims to analyze the results of treatment in a series of 233 gastric cancer patients who underwent a noncurative resection. METHODS: We performed a retrospective study of patients with noncurative treatment for advanced gastric cancer who were divided into three treatment groups: total gastrectomy (TG, n=150), distal gastrectomy (DG, n=44), and nonresection (NR, bypass procedure or chemotherapy only, n=39). RESULTS: In multivariate analysis, surgical treatment (TG) and an absence of chemotherapy were significant independent prognostic factors for a poor survival. In the late period, the overall survival rate was significantly lower in the TG group than in the DG group (p=0.005) and was marginally lower than in the NR group (p=0.054). The resection group had a poorer compliance for chemotherapy than the NR group, and the TG group had a poorer compliance than the DG group (p<0.01). The morbidity rate was higher in the TG group than in the DG group (p<0.05). CONCLUSIONS: TG is considered to be inappropriate for the treatment of noncurative gastric cancer because of the poor prognosis, high morbidity rates, and poor compliance for chemotherapy associated with the procedure. However, noncurative DG was acceptable and postoperative chemotherapy should be used in selected patients. PMID- 22294324 TI - Biological and prognostic associations of miR-205 and let-7b in breast cancer revealed by in situ hybridization analysis of micro-RNA expression in arrays of archival tumour tissue. AB - Micro-RNAs (miRNAs) are frequently dysregulated in a range of human malignancies, many have been shown to act either as tumour supressors or oncogenes and several have been implicated in breast cancer. However, breast cancer is a diverse disease and little is known about the relationships between miRNA expression, clinical outcome and tumour subtype. We used locked nucleic acid probe in situ hybridization (LNA-ISH) to visualize, in tissue micro-arrays (TMAs) of 2919 formalin-fixed paraffin-embedded (FFPE) archival breast tumours, the expression of two key miRNAs that are frequently lost in a range of solid malignancies, let 7b and miR-205. These miRNAs were also quantified by quantitative reverse transcription PCR in cores of FFPE tissue from 40 of these cases, demonstrating that LNA-ISH is semi-quantitative. The tumours in the TMAs were assigned to subtypes based on their immunohistochemical (IHC) staining with ER, PR, HER2, CK5/6 and EGFR. let-7b expression was shown to be associated with luminal tumours and to have an independent significant positive prognostic value in this group. miR-205 is associated with tumours of ductal morphology and is of significant positive prognostic value within these tumours. We propose that the expression of miR-205 may contribute to ductal tumour morphology. PMID- 22294325 TI - Capture and qualitative analysis of the activated Fc receptor complex from live cells. AB - This unit describes the isolation of activated Fc receptor complexes from RAW 264.7 macrophages using live-cell affinity receptor chromatography (LARC). The Fc receptor complex is activated and captured by IgG-coated microbeads on the surface of live macrophages. After the cells are disrupted, the receptor complexes are isolated by washing and sucrose gradient ultracentrifugation. Soluble proteins associated with the receptor complex are then eluted from the beads using a stepwise series of salt buffers and aqueous acetonitrile. The eluted proteins and the residual insoluble proteins on the beads can then be digested with trypsin and subjected to liquid chromatography, electrospray ionization, and tandem mass spectrometry (LC-ESI-MS/MS). Controls include IgG coated beads incubated with crude cell lysates or growth medium and beads coated with oxidized LDL or bovine serum albumin. Using this method, proteins present in IgG-FcR complexes can be distinguished from those in control scavenger receptor complexes (oxLDL or BSA). Thus, LARC is capable of detecting specific members of IgG receptor supramolecular complexes. PMID- 22294326 TI - Introduction to membrane proteins. AB - Membrane proteins (MPs) mediate important physiological processes for the cell via extracellular and intracellular interactions. To better understand the biochemical and structural bases of these interactions, well-characterized preparations of purified MPs are required. This introduction reviews common problems encountered in MP preparation. PMID- 22294327 TI - Overexpression of membrane proteins using Pichia pastoris. AB - Among the small number of expression systems validated for the mass production of eukaryotic membrane proteins (EMPs), the methylotrophic yeast Pichia pastoris stands as one of the most efficient hosts. This system has been used to produce crystallization-grade proteins for a variety of EMPs, from which high-resolution 3D structures have been determined. This unit describes a set of guidelines and instructions to overexpress membrane proteins using the P. pastoris system. Using a G protein-coupled receptor (GPCR) as a model EMP, these protocols illustrate the necessary steps, starting with the design of the DNA sequence to be expressed, through the preparation and analysis of samples containing the corresponding membrane protein of interest. In addition, recommendations are given on a series of experimental parameters that can be optimized to substantially improve the amount and/or the functionality of the expressed EMPs. PMID- 22294328 TI - Radioligand binding analysis as a tool for quality control of GPCR production for structural characterization: adenosine A(2a)R as a template for study. AB - Functional characterization of G protein-coupled receptors is essential to ascertain the suitability of a protein target for downstream studies and to help develop optimal expression and isolation procedures. Radioligand binding analysis is a well-established technique, which allows direct measurement of the amount of functional receptor in a sample. It can be readily applied to both membrane-bound and soluble receptor samples and is an ideal method for monitoring the amount of functional protein at each stage in the expression and isolation process. This unit presents protocols for the radioligand binding analysis of the human adenosine A(2a) receptor and provides examples of how these assays can be used at several stages to help optimize expression, solubilization, and isolation procedures. PMID- 22294329 TI - Purification of the human G protein-coupled receptor adenosine A(2a)R in a stable and functional form expressed in Pichia pastoris. AB - The isolation of membrane proteins with the aim of producing highly pure, homogeneous, stable, and functional material remains challenging, and it is often necessary to develop protein-specific purification protocols by trial and error. One key tool that is required in the development of a suitable protocol is a functional assay. This unit describes a range of different protocols for isolation of the human adenosine A2a receptor (A(2a)R). These protocols show the importance of developing a robust method for comparing the quality of protein obtained by a combination of biophysical analyses including SDS-PAGE, analytical size-exclusion chromatography, and functional analysis. One of the keys to isolating and maintaining a functional receptor, found not only in the optimal protocol described here but in other published examples, is that there should be no more than two chromatographic steps. PMID- 22294330 TI - Silencing of the polyamine catabolic key enzyme SSAT prevents CDK inhibitor induced apoptosis in Caco-2 colon cancer cells. AB - Roscovitine and purvalanol are purine derivative cyclin-dependent kinase (CDK) inhibitors that induce apoptosis in various types of cancer cells. However, their impact on the apoptotic cell death mechanism requires further elucidation. Natural polyamines putrescine, spermidine and spermine play essential roles in the regulation of cell growth and proliferation. Increased levels of polyamines in cells are considered to be involved in cancer progression. Intracellular polyamine levels are under the control of several catabolic enzymes, such as spermidine/spermine-N-acetyl transferase (SSAT), acetylpolyamine oxidase (APAO) and spermine oxidase (SMO), which could be altered by several therapeutic drugs. However, the possible role of polyamines in drug-induced apoptosis has yet to be clarified. In the present study, our aim was to determine the modulation of the polyamine catabolic pathway related to CDK inhibitor-induced apoptosis in Caco-2 cells. We found that roscovitine and purvalanol (each 20 uM) induced apoptosis by activating caspase-9 and -3, and inhibiting the mitochondrial membrane potential in Caco-2 cells. CDK inhibitors decreased the intracellular putrescine and spermine levels without affecting spermidine levels. Although both roscovitine and purvalanol induced SSAT expression, they did not exert a significant effect on the APAO expression profile. SSAT transient silencing prevented roscovitine induced apoptosis compared to parental cells. Thus, we concluded that roscovitine and purvalanol significantly induce apoptosis in Caco-2 cells by modulating the polyamine catabolism, and that SSAT could be an important target in evaluating the potential role of polyamines in apoptotic cell death. PMID- 22294332 TI - Asian motivators for health promotion. AB - Change in health behaviors requires motivation on the part of the individual. The aim of this article is to compare elements of the motivation process across cultures. A secondary aim is to determine whether a Western model of behavior change for health promotion, such as the PRECEDE-PROCEED model, can be applied to Asian populations. An integrative review and critical analysis of research literature was done by reviewing 20 studies with observational survey design and 6 integrative literature reviews. Findings show that the motivation process is similar for Eastern and Western cultures, but the motivators are different. The findings identify 10 motivators, congruent with Asian culture, that would allow the PRECEDE-PROCEED model to be used in Asian settings. PMID- 22294333 TI - Psychometric testing of the Chronic Disease Self-Efficacy Scale-Korean Version (CDSES-K). AB - PURPOSE: To examine the validity and reliability of the Chronic Disease Self Efficacy Scale-Korean Version (CDSES-K) in 380 Korean adults with three chronic diseases: arthritis, diabetes, and hypertension. METHODS: The Korean translated CDSES-K was back-translated to ensure translation equivalency. A methodological research DESIGN: The factor analysis identified eight CDSES-K factors explaining 72.5% of the total variance. The internal consistency reliability for the total instrument was high with Cronbach's alpha of .93. CONCLUSION: The results support the cross-cultural applicability of the concepts underlying the CDSES-K and the self-efficacy transcends across cultures. IMPLICATIONS: The CDSES-K can be used not only to assess self-efficacy in Koreans with chronic diseases but also to examine the potential function of self-efficacy in improvement of self-management behaviors and enhanced health status of people with chronic diseases in a variety of clinical settings. PMID- 22294334 TI - The relationship between acculturation and general health of Arab Americans. AB - PURPOSE: To determine the relationship between acculturation and health status among Arab Americans in southern California. DESIGN: A cross-sectional survey with 297 adult Arab Americans used (a) a demographic and health survey, SF-36 Version-1, to assess physical and mental health and (b) the Acculturation Rating Scale for Arab Americans-II to assess acculturation. FINDINGS: Participants reported significantly better physical health and worse mental health compared to the published norm for the 1998 U.S. population. Better physical health was associated with demographic factors and bicultural identification; better mental health was associated with attraction to American culture. Attraction to American culture predicted alcohol use, whereas attraction to Arabic culture predicted cigarette smoking. CONCLUSION: Different patterns of association existed between acculturation and physical and mental health among Arab Americans. IMPLICATIONS: Findings suggest that acculturation is an important factor to consider in the well-being of Arab Americans, especially in their mental health. PMID- 22294335 TI - Using a virtual community to enhance cultural awareness. AB - PURPOSE: Cultural competence is an expectation of professional practice, yet effectively teaching this concept to nursing students is challenging. The purpose of this study was to assess the use of a virtual community as a teaching application to foster cultural awareness among nursing students. METHOD: This correlational study involved the collection of two surveys from 342 first semester students from five baccalaureate nursing programs that used The Neighborhood virtual community during one semester. Descriptive and comparative analyses were performed. FINDINGS: Results suggest that use of the virtual community may have contributed to cultural awareness among student participants. There was a significant correlation between frequency of use and cultural awareness. Virtual communities may represent a useful teaching application for cultural competence in nursing education. Further research is needed to specifically test cultural competence education strategies using a virtual community platform. PMID- 22294336 TI - Hypertension prevention beliefs of Hispanics. AB - PURPOSE: This qualitative study used focus group methodology to explore attitudes and beliefs of Hispanics regarding hypertension prevention behaviors. METHOD: The sample was composed of 17 participants from varied Hispanic backgrounds. The theory of planned behavior guided interview questions. FINDINGS: Analysis indicated that participants were knowledgeable about and had a positive attitude toward preventing hypertension. However, they identified numerous barriers to preventive behaviors. Two key themes, limited resources (e.g., no time to prepare healthy meals or exercise) and cultural expectations and values (e.g., traditional food as a marker of ethnicity, hospitality, and affection; valuing social interaction over solitary exercise) summarized significant barriers to engaging in recommended preventive behaviors. DISCUSSION: Findings suggest that literature about lack of knowledge about hypertension prevention in Hispanics may be outdated or not applicable to many Hispanics. Select resource and cultural barriers to engaging in hypertension prevention behaviors are important areas to target. IMPLICATIONS: Exercise, stress reduction, and diet modification strategies for hypertension prevention among Hispanics should be consistent with the cultural norms regarding the importance of social interactions and leisure. PMID- 22294337 TI - The influence of marianismo beliefs on physical activity of immigrant Latinas. AB - PURPOSE: To verify and explicate the impact of marianismo beliefs on the physical activity behaviors of immigrant Latinas. DESIGN: Twenty-eight immigrant Latinas, aged 18 to 40 years, were recruited to participate in two focus group interviews. Data collection and analysis were driven by Spradley's Developmental Research Sequence. RESULTS: Two domain terms were identified: "Life is too fast here" and "The woman is the center of the family." Six included terms and five cultural themes were specified. DISCUSSION: A combination of marianismo beliefs, acculturation stress, loss of social support, and conflicts between collectivist and individualist values combine to adversely influence physical activity behaviors of immigrant Latinas. IMPLICATIONS: Physical activity interventions for Hispanic women should capitalize on the strengths of the marianista, address factors leading to acculturation stress among women and their families, and establish bridges of social support among new groups of immigrants. PMID- 22294338 TI - Culture and smoking among Vietnamese Americans in central Massachusetts. AB - The study was conducted (a) to assess use of any smoking cessation medications, (b) to identify factors associated with smoking, and (c) to assess knowledge of the health effects of smoking and attitudes toward smoking and seeking help for quitting among Vietnamese Americans. This is a descriptive study conducted with a nonrepresentative sample of 163 Vietnamese Americans. Current and former smokers constituted 24.4% and 25.6% of men and 1.2% and 3.5% of women, respectively. Of 20 current smokers, 17 (85%) reported use of cessation medications in their past quit attempts. Acculturation was the only significant correlate of ever smoking (vs. never smoking) in multivariate logistic regression analyses. Men who were less acculturated had more than 5 times the odds of being ever smokers (odds ratio = 5.33, 95% confidence interval = 1.37-20.78) compared with more acculturated men. Most participants had correct knowledge of the health effects of smoking regardless of age, education level, and smoking status. Attitudes toward smoking differed by age and education level but not by smoking status. Nurses working with Vietnamese Americans should be aware of the high rate of smoking among male immigrants and provide smoking cessation interventions. PMID- 22294339 TI - Postpartum depression and parental self-efficacy: a comparison of native Korean and Vietnamese immigrant mothers in Korea. AB - PURPOSE: This study compared postpartum depression and parental self-efficacy between married immigrant women from Vietnam and native Korean mothers. METHOD: The participants were 72 native Korean mothers and 69 immigrant Vietnamese mothers living in a suburban city in South Korea. The instruments used were the Edinburgh Postnatal Depression Scale and the Parent Expectation Survey. RESULTS: There were statistically significant differences in age, education, employment, income, husband's age, and family structure between the two groups. Immigrant Vietnamese mothers experienced higher levels of postpartum depression (t = 3.466, p = .001) and had lower parental self-efficacy (t = 5.607, p < .001) than native Korea mothers. Postpartum depression was negatively correlated with parental self-efficacy in native Korean mothers (r = -.349, p = .003), but there was no significant correlation in the immigrant Vietnamese mothers (r = .011, p = .936). The mothers' country of origin, whether immigrant or Korean, was a significant factor in postpartum depression (beta = .338, p = .040; R (2) = .091). The mothers' country of origin had no effect on parental self-efficacy (p = .957). Instead, significant differences were found for the age, education level, and family structure of the participant (R (2) = .036). CONCLUSIONS: The results of this study demonstrated that postpartum depression was more prevalent among married immigrant women from Vietnam than among native Korean mothers. Accordingly, a postpartum depression intervention program for married immigrant women should be developed and implemented. PMID- 22294340 TI - Clinically compatible MRI strategies for discriminating bound and pore water in cortical bone. AB - Advances in modern magnetic resonance imaging (MRI) pulse sequences have enabled clinically practical cortical bone imaging. Human cortical bone is known to contain a distribution of T(1) and T(2) components attributed to bound and pore water, although clinical imaging approaches have yet to discriminate bound from pore water based on their relaxation properties. Herein, two clinically compatible MRI strategies are proposed for selectively imaging either bound or pore water by utilizing differences in their T(1)s and T(2)s. The strategies are validated in a population of ex vivo human cortical bones, and estimates obtained for bound and pore water are compared to bone mechanical properties. Results show that the two MRI strategies provide good estimates of bound and pore water that correlate to bone mechanical properties. As such, the strategies for bound and pore water discrimination shown herein should provide diagnostically useful tools for assessing bone fracture risk, once applied to clinical MRI. PMID- 22294341 TI - Essential oil of Juniperus communis subsp. alpina (Suter) Celak needles: chemical composition, antifungal activity and cytotoxicity. AB - Essential oils are known to possess antimicrobial activity against a wide spectrum of bacteria and fungi. In the present work the composition and the antifungal activity of the oils of Juniperus communis subsp. alpina (Suter) Celak were evaluated. Moreover, the skin cytotoxicity, at concentrations showing significant antifungal activity, was also evaluated. The oils were isolated by hydrodistillation and analysed by gas chromatography and gas chromatography-mass spectrometry. Minimal inhibitory concentration (MIC) and minimal lethal concentration (MLC) were used to evaluate the antifungal activity of the oil against dermatophytes (Epidermophyton floccosum, Microsporum canis, M. gypseum, Trichophyton mentagrophytes, T. mentagrophytes var. interdigitale, T. rubrum, T. verrucosum), yeasts (Candida albicans, C. guillermondii, C. krusei, C. parapsilosis, C. tropicalis, Cryptococcus neoformans) and Aspergillus species (Aspergillus flavus, A. fumigatus, A. niger). Cytotoxicity was tested in HaCaT keratinocytes through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Essential oil of J. communis subsp. alpina needles was predominantly composed of monoterpene hydrocarbons (78.4%), with the main compounds being sabinene (26.2%), alpha-pinene (12-9%) and limonene (10.4%). Results concerning the antifungal activity demonstrated the potential of needle oil against dermatophytes, particularly for Microsporum canis and Trichophyton rubrum with MIC and MLC of 0.32 MUL/mL. Furthermore, evaluation of cell viability showed no significant cytotoxicity in HaCaT keratinocytes at concentrations between 0.32 and 0.64 MUL/mL. These results show that it is possible to find appropriate doses of J. communis subsp. alpina oil with both antifungal activity and a very low detrimental effect on keratinocytes. PMID- 22294342 TI - Development of metastatic Crohn's disease of the skin while on anti-TNF biologics. PMID- 22294343 TI - Coil-to-helix transitions in intrinsically disordered methyl CpG binding protein 2 and its isolated domains. AB - Methyl CpG binding protein 2 (MeCP2) is a canonical intrinsically disordered protein (IDP), that is, it lacks stable secondary structure throughout its entire polypeptide chain. Because IDPs often have the propensity to become locally ordered, we tested whether full-length MeCP2 and its constituent domains would gain secondary structure in 2,2,2-trifluoroethanol (TFE), a cosolvent that stabilizes intramolecular hydrogen bonding in proteins. The alpha-helix, beta strand/turn, and unstructured content were determined as a function of TFE concentration by deconvolution of circular dichroism data. Results indicate that approximately two-thirds of the unstructured residues present in full-length MeCP2 were converted to alpha-helix in 70% TFE without a change in beta strand/turn. Thus, much of the MeCP2 polypeptide chain undergoes coil-to-helix transitions under conditions that favor intrachain hydrogen bond formation. The unstructured residues of the N-terminal (NTD) and C-terminal (CTD) domains were partially converted to alpha-helix in 70% TFE. In contrast, the central transcription regulation domain (TRD) became almost completely alpha-helical in 70% TFE. Unlike the NTD, CTD, and TRD, the unstructured content of the methyl DNA binding domain and the intervening domain did not change with increasing TFE concentration. These results indicate that the coil-to-helix transitions that occur in full-length MeCP2 are localized to the NTD, CTD, and TRD, with the TRD showing the greatest tendency for helix formation. The potential relationships between intrinsic disorder, coil-to-helix transitions, and MeCP2 structure and function are discussed. PMID- 22294344 TI - Sustained response and prevention of damage progression in patients with neonatal onset multisystem inflammatory disease treated with anakinra: a cohort study to determine three- and five-year outcomes. AB - OBJECTIVE: Blocking interleukin-1 with anakinra in patients with the autoinflammatory syndrome neonatal-onset multisystem inflammatory disease (NOMID) reduces systemic and organ-specific inflammation. However, the impact of long term treatment has not been established. This study was undertaken to evaluate the long-term effect of anakinra on clinical and laboratory outcomes and safety in patients with NOMID. METHODS: We conducted a cohort study of 26 NOMID patients ages 0.80-42.17 years who were followed up at the NIH and treated with anakinra 1 5 mg/kg/day for at least 36 months. Disease activity was assessed using daily diaries, questionnaires, and C-reactive protein level. Central nervous system (CNS) inflammation, hearing, vision, and safety were evaluated. RESULTS: Sustained improvements in diary scores, parent's/patient's and physician's global scores of disease activity, parent's/patient's pain scores, and inflammatory markers were observed (all P<0.001 at 36 and 60 months). At 36 and 60 months, CNS inflammation was suppressed, with decreased cerebrospinal fluid white blood cell counts (P=0.0026 and P=0.0076, respectively), albumin levels, and opening pressures (P=0.0012 and P<0.001, respectively). Most patients showed stable or improved hearing. Cochlear enhancement on magnetic resonance imaging correlated with continued hearing loss. Visual acuity and peripheral vision were stable. Low optic nerve size correlated with poor visual field. Bony lesions progressed. Adverse events other than viral infections were rare, and all patients continued to receive the medication. CONCLUSION: These findings indicate that anakinra provides sustained efficacy in the treatment of NOMID for up to 5 years, with the requirement of dose escalation. Damage progression in the CNS, ear, and eye, but not bone, is preventable. Anakinra is well tolerated overall. PMID- 22294345 TI - Optimizing the osteogenicity of nanotopography using block co-polymer phase separation fabrication techniques. AB - Both temporary and permanent orthopedic implants have, by default or design, surface chemistry, and topography. There is increasing evidence that controlling nanodisorder can result in increased osteogenesis. Block co-polymer phase separation can be used to fabricate a nanotopography exhibiting a controlled level of disorder, both reproducibly and cost-effectively. Two different topographies, produced through the use of block co-polymer phase separation, were embossed onto the biodegradable thermoplastic, polycaprolactone (PCL). Analysis of the topography itself was undertaken with atomic force microscopy, and the topography's effect on human osteoblasts studied through the use of immunocytochemistry and fluorescence microscopy. Planar controls had a surface roughness 0.93 nm, and the substrates a high fidelity transfer of a disordered pattern of 14 and 18 nm. Cytoskeletal organization and adhesion, and increased expression of Runx2 were significantly greater on the smallest nanotopography. Expression of osteopontin and osteocalcin protein, and alizarin red staining of bone nodules were greatest on the smallest feature nanopatterns. Highly osteogenic, disordered nanotopographies can be manufactured into thermoplastics in a rapid and cost-effective way through the use of block co-polymer phase separation. Osteogenic topographies reproducibly and cost-effectively produced have a potentially useful application to the fields of implant technology and regenerative orthopedics. PMID- 22294346 TI - Severe obstructive sleep apnea increases mortality in patients with ischemic heart disease and myocardial injury. AB - OBJECTIVES: We hypothesized that obstructive sleep apnea(OSA) has a dose dependent impact on mortality in those with ischemic heart disease or previous myocardial injury. METHODS: We performed a retrospective cohort study of 281 consecutive OSA patients with a history of myocardial injury as determined by elevated troponin levels or with known existing ischemic heart disease. We compared survival between those with severe OSA [apnea-hypopneaindex (AHI) >=30] and those with mild to moderate OSA(AHI >5 and <30). RESULTS: Of the 281 patients (mean age 65 years, mean BMI34, 98% male, 58% with diabetes), 151 patients had mild moderate OSA and 130 had severe OSA. During a mean follow-up of 4.1 years, there were significantly greater deaths in the severe OSA group compared to the mild moderate OSA group [53 deaths (41%) vs. 44 deaths(29%), respectively, p00.04]. The adjusted hazard ratio for mortality with severe OSA was 1.72 (95% confidence interval1.01-2.91, p00.04). CONCLUSIONS: The severity of obstructive sleep apnea is associated with increased risk of death, and risk stratification based on OSA severity is relevant even in the diseased cardiac patient. PMID- 22294347 TI - Hypothalamic mTOR pathway mediates thyroid hormone-induced hyperphagia in hyperthyroidism. AB - Hyperthyroidism is characterized in rats by increased energy expenditure and marked hyperphagia. Alterations of thermogenesis linked to hyperthyroidism are associated with dysregulation of hypothalamic AMPK and fatty acid metabolism; however, the central mechanisms mediating hyperthyroidism-induced hyperphagia remain largely unclear. Here, we demonstrate that hyperthyroid rats exhibit marked up-regulation of the hypothalamic mammalian target of rapamycin (mTOR) signalling pathway associated with increased mRNA levels of agouti-related protein (AgRP) and neuropeptide Y (NPY), and decreased mRNA levels of pro opiomelanocortin (POMC) in the arcuate nucleus of the hypothalamus (ARC), an area where mTOR co-localizes with thyroid hormone receptor-alpha (TRalpha). Central administration of thyroid hormone (T3) or genetic activation of thyroid hormone signalling in the ARC recapitulated hyperthyroidism effects on feeding and the mTOR pathway. In turn, central inhibition of mTOR signalling with rapamycin in hyperthyroid rats reversed hyperphagia and normalized the expression of ARC derived neuropeptides, resulting in substantial body weight loss. The data indicate that in the hyperthyroid state, increased feeding is associated with thyroid hormone-induced up-regulation of mTOR signalling. Furthermore, our findings that different neuronal modulations influence food intake and energy expenditure in hyperthyroidism pave the way for a more rational design of specific and selective therapeutic compounds aimed at reversing the metabolic consequences of this disease. PMID- 22294348 TI - UPLC-MS metabolic profiling of second trimester amniotic fluid and maternal urine and comparison with NMR spectral profiling for the identification of pregnancy disorder biomarkers. AB - We report on the first untargeted UPLC-MS study of 2nd trimester maternal urine and amniotic fluid (AF), to investigate the possible metabolic effects of fetal malformations (FM), gestational diabetes mellitus (GDM) and preterm delivery (PTD). For fetal malformations, considerable metabolite variations were identified in AF and, to a lesser extent, in urine. Using validated PLS-DA models and statistical correlations between UPLC-MS data and previously acquired NMR data, a metabolic picture of fetal hypoxia, enhanced gluconeogenesis, TCA activity and hindered kidney development affecting FM pregnancies was reinforced. Moreover, changes in carnitine, pyroglutamate and polyols were newly noted, respectively, reflecting lipid oxidation, altered placental amino acid transfer and alterations in polyol pathways. Higher excretion of conjugated products in maternal urine was seen suggesting alterations in conjugation reactions. For the pre-diagnostic GDM group, no significant changes were observed, either considering amniotic fluid or maternal urine, whereas, for the pre-PTD group, some newly observed changes were noted, namely, the decrease of particular amino acids and the increase of an hexose (possibly glucose), suggesting alteration in placental amino acid fluxes and a possible tendency for hyperglycemia. This work shows the potential of UPLC-MS for the study of fetal and maternal biofluids, particularly when used in tandem with comparable NMR data. The important roles played by sampling characteristics (e.g. group dimensions) and the specific experimental conditions chosen for MS methods are discussed. PMID- 22294349 TI - Comparative assessment of 5 methods (methylation-specific polymerase chain reaction, MethyLight, pyrosequencing, methylation-sensitive high-resolution melting, and immunohistochemistry) to analyze O6-methylguanine-DNA methyltranferase in a series of 100 glioblastoma patients. AB - BACKGROUND: There is a strong need to determine the best technique for O(6) methylguanine-DNA-methyltranferase (MGMT) analysis, because MGMT status is currently used in clinical trials and occasionally in routine clinical practice for glioblastoma patients. METHODS: The authors compared analytical performances and predictive values of 5 techniques in a series of 100 glioblastoma patients who received standard of care treatment (Stupp protocol). RESULTS: MGMT promoter was considered methylated in 33%, 33%, 42%, and 60% of patients by methylation sensitive high-resolution melting, MethyLight, pyrosequencing (with an optimal risk cutoff at 8% for the average percentage of the 5 CpGs tested), and methylation-specific polymerase chain reaction (MS-PCR), respectively. Fifty-nine percent of the samples had <23% (the optimal risk cutoff) of MGMT-positive tumor cells. The best predictive values for overall survival (OS), after adjustment for age and performance status, were obtained by pyrosequencing (hazard ratio [HR], 0.32; P < .0001), MS-PCR (HR, 0.37; P < .0001), and immunohistochemistry (HR, 0.43; P = .0005) as compared with methylation-sensitive high-resolution melting (HR, 0.52 P = .02) and MethyLight (HR, 0.6; P = .05). For progression-free survival (PFS), the best predictive values were obtained with pyrosequencing (HR, 0.35; P < .0001), methylation-sensitive high-resolution melting (HR, 0.46; P = .002), and MS-PCR (HR, 0.49; P = .002). Combining pyrosequencing and immunohistochemistry slightly improved predictive power for OS, but not for PFS. Poor reproducibility and interobserver variability were, however, observed for immunohistochemistry. CONCLUSIONS: Good prediction of survival in addition to high reproducibility and sensitivity made pyrosequencing the best among the 5 techniques tested in this study. PMID- 22294351 TI - Cranberry juice extract, a mild prooxidant with cytotoxic properties independent of reactive oxygen species. AB - A cranberry juice extract (CJE), rich in proanthocyanidins, had weak prooxidant properties, generating low levels of hydrogen peroxide (H2O2) and superoxide. Generation of H2O2 was pH dependent, increasing at alkaline pH, and was lowered in the presence of catalase and, to a lesser extent, of superoxide dismutase (SOD). Growth inhibition and cytotoxicity were noted towards human oral carcinoma HSC-2 cells, with midpoint cytotoxicity at 200 ug/mL CJE, but not towards human gingival HF-1 fibroblasts. Being a mild prooxidant, CJE toxicity was unaffected by exogenous catalase and pyruvate, scavengers of H2O2, but triggered intracellular synthesis of reduced glutathione, as confirmed by cell staining with Cell TrackerTM Green. The presence of exogenous SOD potentiated the toxicity of CJE, possibly by stabilizing the CJE phenols and hindering their degradative autooxidation. Conversely, 'spent' CJE, i.e. CJE added to cell culture medium and incubated for 24 h at 37 degrees C prior to use, was much less toxic to HSC-2 cells than was freshly prepared CJE. These differences in toxicity between SOD stabilized CJE, freshly prepared CJE, and 'spent' CJE were confirmed in HSC-2 cells stained with aceto-orcein, which also indicated that the mode of cell death was by the induction of apoptosis. PMID- 22294350 TI - Detecting false-positive signals in exome sequencing. AB - Disease gene discovery has been transformed by affordable sequencing of exomes and genomes. Identification of disease-causing mutations requires sifting through a large number of sequence variants. A subset of the variants are unlikely to be good candidates for disease causation based on one or more of the following criteria: (1) being located in genomic regions known to be highly polymorphic, (2) having characteristics suggesting assembly misalignment, and/or (3) being labeled as variants based on misleading reference genome information. We analyzed exome sequence data from 118 individuals in 29 families seen in the NIH Undiagnosed Diseases Program (UDP) to create lists of variants and genes with these characteristics. Specifically, we identified several groups of genes that are candidates for provisional exclusion during exome analysis: 23,389 positions with excess heterozygosity suggestive of alignment errors and 1,009 positions in which the hg18 human genome reference sequence appeared to contain a minor allele. Exclusion of such variants, which we provide in supplemental lists, will likely enhance identification of disease-causing mutations using exome sequence data. PMID- 22294352 TI - Simulation of head-gradient-coil induced electric fields in a human model. AB - A finite difference method was used to simulate the electric fields induced in the model by a gradient wire pattern. The pattern simulated corresponded to a design used to perform peripheral nerves stimulation experiments. The size (187.8, 169.02, and 150.24 cm tall) and position (brain and neck mode) of the model, relative to the magnet, as well as the voxel dimensions (3, 6, and 9 mm) of the model were varied to assess the effect on the simulation. The locations of stimulation reported from an experiment were classified according to nerve branch and compared with the peak-simulated electric fields. Model size and location affected the magnitude of the electric field, but not the position. Model resolution affected the location of the peak field. For the smallest resolution investigated, the nerves affected by the locations of peak stimulations in the model correlated to the frequency of stimulation in experiments. Although adequate resolution is required in order to assess the electric fields induced by gradient coil operation, the simulation of electric fields may be useful in evaluating gradient coil design prior to construction. PMID- 22294355 TI - Induction of unexpected left-handed helicity by an N-terminal L-amino acid in an otherwise achiral peptide chain. PMID- 22294356 TI - Direct titanium-mediated conversion of ketones into enamides with ammonia and acetic anhydride. PMID- 22294357 TI - Gold(I)-catalyzed enantioselective intramolecular dehydrative amination of allylic alcohols with carbamates. PMID- 22294358 TI - Controlling the self-assembly of metal-seamed organic nanocapsules. PMID- 22294359 TI - Conversion of Sb2Te3 hexagonal nanoplates into three-dimensional porous single crystal-like network-structured Te plates using oxygen and tartaric acid. PMID- 22294360 TI - Supramolecular polymerization triggered by molecular recognition between bisporphyrin and trinitrofluorenone. PMID- 22294361 TI - Lewis base stabilized dicarbon: predictions from theory. PMID- 22294363 TI - In vitro muscarinic receptor radioligand-binding assays. AB - G-protein-coupled muscarinic receptors (mAChRs), of which there are five subtypes (M(1)-M(5)), are attractive drug targets for a number of disorders. Described in this unit are radioligand-binding assays for defining the selectivity and affinity of chemical agents at the five mAChR subtypes. Detailed methodologies and troubleshooting strategies are provided for saturation-binding studies, to estimate K(D) and B(max) values, and for competition-binding studies to estimate K(i) values. Emphasis is placed on experimental details that are critical for executing a robust and reliable assay. PMID- 22294364 TI - In vivo pharmacodynamic assays for M2 and M3 muscarinic receptors. AB - M(2) and M(3) muscarinic receptor subtypes are attractive drug targets for the treatment of pulmonary and urological disorders. Described in this unit is an in vivo pithed rat assay for estimating agonist and antagonist potency at M(2) and M(3) receptors. In the pithed rat, the muscarinic agonist methacholine induces reduction in heart rate (bradycardia) and blood pressure (depressor response) through interaction with M(2) and M(3) receptors, respectively. The dissociation of the peripheral and central nervous system in the pithed rat preparation permits the direct assessment of compound effects on the heart and vasculature in the absence of cardiovascular reflexes. Estimates of antagonist potency can be reliably established by quantifying the shift in the agonist dose-effect curve produced under appropriate equilibrium or non-equilibrium conditions. PMID- 22294365 TI - Static biofilm cultures of Gram-positive pathogens grown in a microtiter format used for anti-biofilm drug discovery. AB - An in vitro assay is presented for culturing staphylococcal biofilms and biofilms of nonmotile Gram-positive bacteria under static conditions in microtiter assay plates, and for the quantification of biofilm growth, using a simple staining procedure that measures amounts of bacterial cells and extracellular matrix. This basic assay can be adapted readily to study several aspects of biofilm formation, for high-throughput screening to identify small molecule inhibitors of biofilm formation or biofilm-defective mutants, and for quantifying the anti-biofilm activity of biofilm inhibitors. PMID- 22294366 TI - Evaluation of compound activity against hepatitis C virus in replicon systems. AB - Described in this unit are protocols for evaluation of new chemical entities for activity against hepatitis C virus (HCV) using HCV replicon systems. While agents designed to target NS3 protease, NS3 helicase, and NS5B RNA polymerase can be evaluated in biochemical assays, it is important to confirm their inhibitory effect on HCV RNA replication using HCV replicon systems, especially since replication involves many components besides these enzymes. Screening of compound libraries using replicon systems has led to the discovery of replication inhibitors, which act through different viral targets. PMID- 22294367 TI - Studies on hepatitis C virus resistance to inhibitors in replicon systems. AB - Viruses evolve under selection pressure from a particular antiviral agent, resulting in the emergence of organisms that are not susceptible to the drug. This process is referred to as "virus resistance induction." While conventional in vitro resistance studies are conducted using infectious viruses, the lack of a robust hepatitis C virus (HCV) infection system in cell culture makes such an approach impossible in this case. Instead, cell lines harboring a self replicating HCV RNA (or HCV replicon) are used for this purpose. The protocols detailed in this unit describe methods for studying HCV resistance to inhibitors, including the selection of replicon variants resistant to HCV inhibitors, characterization of these variants for their phenotypes and genotypes, and determination of the role of the mutation(s) identified in their genomes. The results from such studies are not only important for lead identification and confirmation of drug targets, but also aid in monitoring the appearance of resistant variants in clinical settings. PMID- 22294368 TI - Mouse models of human bladder cancer as a tool for drug discovery. AB - Muscle-invasive bladder cancer is a deadly condition in dire need of effective new treatments. This unit contains a description of mouse models suitable for the evaluation of potential new therapies. Included is a genetically engineered mouse model of bladder cancer generated by the delivery of an adenovirus expressing Cre recombinase into the bladder lumen. Also described is an orthotopic mouse model created by the instillation of human bladder tumor cells into the bladder lumen of immune deficient mice. Protocols are also provided on the use of these models for the preclinical evaluation of new chemical entities, with mTOR inhibitors shown as an example. PMID- 22294369 TI - Cyclic nucleotide phosphodiesterase assay technology. AB - Because of their critical role in modulating cellular cyclic nucleotide levels, phosphodiesterases (PDEs) are involved in many disease-related signaling pathways. The PDE family is large and diverse, with members having different tissue distribution, sub-cellular localizations, and substrate specificities. Because of these characteristics, the PDEs represent a broad group of potential drug targets. Described in the present unit are the assay development and validation procedures needed to establish a high-throughput screening system for these important enzymes. The assays provide a structured approach for determining the kinetic parameters of related enzyme families to facilitate the characterization of PDE inhibitors. PMID- 22294370 TI - Tachykinin receptor assays. AB - Described in this unit are methods for obtaining, preparing, and testing smooth muscle preparations bearing tachykinin receptors to study the agonist or antagonist properties of test compounds. Concentration-response curves to agonists are constructed to measure their ability to produce smooth muscle contractions and thus evaluate the potency and efficacy of the agonists. Antagonists are tested for their ability to shift the agonist concentration response curve and to calculate their potency. Two different protocols are described for each of the three tachykinin receptors (NK(1), NK(2), and NK(3)). The NK(1) receptor assays use guinea pig ileum longitudinal muscle myenteric plexus (GPI) and rat urinary bladder (RUB), the NK(2) receptor assays use isolated endothelium-deprived rabbit pulmonary artery (RPA) and hamster trachea (HT), and the NK(3) receptor assays use GPI and rat portal vein (RPV). PMID- 22294371 TI - In vitro isolated tissue functional muscarinic receptor assays. AB - Muscarinic receptor (mAChRs) subtypes are viable targets for the design of novel agents for use in a number of central and peripheral disorders. In vitro isolated tissue functional assays for muscarinic receptor subtypes have played an invaluable role in basic research and drug discovery. The availability of biological assays for generation of quantitative estimates of affinity and potency of ligands allows evaluation of the contribution of a given mAChR to the functional end organ response and also enables drug discovery by facilitating the iterative process of screening and optimization of chemical leads. This unit describes isolated tissue functional assays for the quantification of ligand affinity and efficacy at the M(1), M(2), M(3), M(4), and M(5) muscarinic receptor subtypes in tissues expressing the native receptor using organ bath techniques. PMID- 22294372 TI - Novel object recognition in the rat: a facile assay for cognitive function. AB - The rat novel object recognition (NOR) assay is a relatively high-throughput, robust, and sensitive procedure for evaluating compounds for cognition-enhancing activity. For the test, rats are given the opportunity to explore two identical objects for a predetermined period of time. After a delay, the animals are then presented with two objects to explore, one of which is the same as in the first exploration trial, the other a new object. Depending on the length of the delay between the two trials, the rats will either explore the novel object for a greater time period, indicating memory for the familiar object, or will explore the novel and familiar objects for the same amount of time, indicating a lack of recall or loss of memory for the familiar object presented during the initial trial. The protocol described in this unit can be used to evaluate the effects of a compound on the short-term/working memory of adult male rats following a 24-hr inter-trial interval. PMID- 22294373 TI - Rodent models of depression: forced swim and tail suspension behavioral despair tests in rats and mice. AB - The development of antidepressants requires simple rodent behavioral tests for initial screening before undertaking more complex preclinical tests and clinical evaluation. Presented in the unit are two widely used screening tests used for antidepressants, the forced swim (also termed behavioral despair) test in the rat and mouse, and the tail suspension test in the mouse. These tests have good predictive validity and allow rapid and economical detection of substances with potential antidepressant-like activity. The behavioral despair and the tail suspension tests are based on the same principle: measurement of the duration of immobility when rodents are exposed to an inescapable situation. The majority of clinically used antidepressants decrease the duration of immobility. Antidepressants also increase the latency to immobility, and this additional measure can increase the sensitivity of the behavioral despair test in the mouse for certain classes of antidepressant. Testing of new substances in the behavioral despair and tail suspension tests allows a simple assessment of their potential antidepressant activity by the measurement of their effect on immobility. PMID- 22294374 TI - Pharmacological applications of baculovirus-mediated protein expression in mammalian cells. AB - The development of cell-based assays for cellular receptors, ion channels, and transporters requires the delivery and expression of transgenes. Viral-mediated gene delivery is a particularly attractive approach for this purpose because of its efficiency and potential to deliver genes to a wide variety of cell types. Recombinant baculoviruses, long used to deliver genes to insect cells for overexpression, also effectively transfer genes to mammalian cells. The only required modification to the virus for this purpose is the addition of transgene expression cassettes controlled by mammalian cell-active promoters. These so called BacMam viruses are useful for developing mammalian cell-based assays for investigating the function of recombinant proteins and for assessing the action of pharmacological modulators of their function. The use of such viruses is gaining popularity because of the ease of optimizing assay conditions, the ability to deliver multiple gene products, and of their flexibility in terms of host cells and levels of transgene expression. BacMam-mediated assays may be used for studying a wide variety of target proteins and assay technologies. Described in this unit is an example of BacMam-mediated gene delivery to configure a cell based assay for pharmacological assessment of a G protein-coupled receptor. A protocol is also provided describing the use of a GFP-expressing BacMam to assess the susceptibility of new cell lines to transduction by the virus. PMID- 22294375 TI - Overview on the Rule of Five. AB - In the mid- to late 1990 s, because of the drug discovery paradigm shift from phenotypic screens to combinatorial chemistry and high-throughput screening, the physicochemical properties of exploratory drug molecules displayed a dramatic shift toward higher molecular weight and lipophilicity. In response, Lipinski and coworkers reported an analysis of compounds that successfully navigated Phase I and entered into Phase II clinical studies, and correlated the computed physicochemical properties of these molecules to their aqueous solubility, permeability, and oral bioavailability. In doing so, the authors created the "Rule of Five," a mnemonic tool for medicinal chemists to use to quickly assess compounds during the drug discovery and optimization process with respect to the compounds' likelihood to display good solubility and permeability profiles. This overview outlines the basis for the Rule of Five, the ways in which it has been applied, and its impact on drug discovery and development. PMID- 22294376 TI - Label-free imaging and temporal signature in phenotypic cellular assays: a new approach to high-content screening. AB - Some drug targets are not amenable to screening because of the lack of a practical or validated biological assay. Likewise, some screening assays may not be predictive of compound activity in a more disease-relevant scenario, or assay development may demand excessive allocation of resources (i.e., time, money or personnel) with limited knowledge of the actual tractability of the target. Label free methodologies, implemented in microtiter plate format, may help address these issues and complement, simplify, or facilitate assays. Label-free biosensors, based on grating resonance or electrical impedance, are versatile platforms for detecting phenotypic changes in both engineered and native cells. Their non-invasive nature allows for the kinetic monitoring of multiple real-time cellular responses to external stimuli, as well as for the use of successive pharmacological challenges. The temporal signature recorded for a particular stimulus is characteristic of the cell type and the signaling pathway activated upon binding of a ligand to its receptor. Cellular label-free technology is an important technical advance in the study of functional pharmacological selectivity. Described in this overview are some of the hurdles encountered in modern drug discovery and the ways in which label-free technologies can be used to overcome these obstacles. PMID- 22294377 TI - Measuring receptor target coverage: a radioligand competition binding protocol for assessing the association and dissociation rates of unlabeled compounds. AB - The kinetics of the ligand-receptor interaction is an important feature in lead optimization for new drug candidates. The protocol described in this unit is a kinetic radioligand competition binding assay that makes possible the determination of both the association and dissociation rates of unlabeled receptor ligands. PMID- 22294378 TI - An energy-saving glutathione production method from low-temperature cooked rice using amylase-expressing Saccharomyces cerevisiae. AB - Glutathione is a valuable tripeptide that is widely used in the pharmaceutical, food, and cosmetic industries. Glutathione is industrially produced by fermentation using Saccharomyces cerevisiae. Before the glutathione fermentation process with S. cerevisiae, a glucose extraction process from starchy materials is required. This glucose extraction is usually carried out by converting starchy materials to starch using high-temperature cooking and subsequent hydrolysis by amylases to convert starch to glucose. In this study, to develop an energy-saving glutathione production process by reducing energy consumption during the cooking step, we efficiently produced glutathione from low-temperature cooked rice using amylase-expressing S. cerevisiae. The combination of the amylase-expressing yeast with low-temperature cooking is potentially applicable to a variety of energy saving bio-production methods of chemicals from starchy bio-resources. PMID- 22294379 TI - Changes in lymphocyte HSP70 levels in women handball players throughout 1 year of training: the role of estrogen levels. AB - Heat shock protein 70 (HSP70) is a chaperone that maintains protein conformation during heat stress. It has recently been observed that HSP70 may be released from cells in response to increased energy demand (e.g., exercise) and/or oxidative stress. Since HSP70 levels should change in response to athletic training, we have investigated whether blood HSP70 levels in young women handball players change over a complete training season. Thirty women handball players (12-24 years old) were divided into low (>=30 pg mL(-1)) (LE) and normal (30-330 pg mL( 1)) (NE) estradiol groups. HSP70 levels in lymphocytes and plasma and blood redox parameters were evaluated over 1 year (2009), with sampling at the beginning, middle, and end of the season. We observed no changes in superoxide dismutase activity or protein carbonyl or extracellular HSP70 levels, while catalase activity increased at the middle of the season in the NE group, and the thiobarbituric acid species levels in both groups were higher at the beginning of the season than at the middle or end. The lymphocyte HSP70 content was higher at the middle and end than at the beginning of the season in the NE group and also higher in the LE group than in the NE group at the beginning of the season. These results suggest that plasma estradiol levels may play an important role in exercise training and that the intracellular HSP70 content, a biomarker for inflammation, is affected by both estradiol levels and exercise-induced oxidative stress. PMID- 22294380 TI - Efficacy of a porous-structured titanium subdermal barrier for preventing infection in percutaneous osseointegrated prostheses. AB - Infections of percutaneous osseointegrated prostheses (POP) cause prolonged morbidity and device failure because once established, they are refractory to antibiotic therapy. To date, only limited translational animal studies have investigated the efficacy of POP designs in preventing infections. We developed an animal model to evaluate the efficacy of a porous-coated titanium (Ti) subdermal barrier to achieve skin-implant integration and to prevent periprosthetic infection. In a single-stage "amputation and implantation" surgery, 14 sheep were fitted with percutaneous devices with an attached porous coated Ti subdermal barrier. Nine sheep were implanted with a smooth Ti subdermal barrier construct and served as controls, with one control sheep removed from the study due to a fractured bone. Clinical, microbiological, and histopathological data showed that the porous Ti barrier prevented superficial and deep tissue infections in all animals (14/14, 100%) at the 9-month endpoint. In contrast, animals with the smooth Ti implant construct had a 25% (2/8) infection rate. Survival analysis indicated a significant difference between the groups (log-rank test, p = 0.018). Data also indicated that although skin marsupialization was evident in both implant types, animals in the control group had a four times greater marsupialization rate. We concluded that osseointegrated implants incorporating porous-coated Ti subdermal barriers may have the ability to prevent infection by maintaining a healthy, biologically attached epithelial barrier at the skin-implant interface in load-bearing animals up to a 9-month terminus. PMID- 22294381 TI - Disease activity, severity, and damage in the UK Juvenile-Onset Systemic Lupus Erythematosus Cohort. AB - OBJECTIVE: The UK Juvenile-Onset Systemic Lupus Erythematosus (JSLE) Cohort Study is a multicenter collaborative network established with the aim of improving the understanding of juvenile SLE. The present study was undertaken to describe the clinical manifestations and disease course in patients with juvenile SLE from this large, national inception cohort. METHODS: Detailed data on clinical phenotype were collected at baseline and at regular clinic reviews and annual followup assessments in 232 patients from 14 centers across the UK over 4.5 years. Patients with SLE were identified according to the American College of Rheumatology (ACR) SLE classification criteria. The present cohort comprised children with juvenile SLE (n=198) whose diagnosis fulfilled >=4 of the ACR criteria for SLE. RESULTS: Among patients with juvenile SLE, the female:male sex distribution was 5.6:1 and the median age at diagnosis was 12.6 years (interquartile range 10.4-14.5 years). Male patients were younger than female patients (P<0.01). Standardized ethnicity data demonstrated a greater risk of juvenile SLE in non-Caucasian UK patients (P<0.05). Scores on the pediatric adaptation of the 2004 British Isles Lupus Assessment Group disease activity index demonstrated significantly increased frequencies of musculoskeletal (82%), renal (80%), hematologic (91%), immunologic (54%), and neurologic (26%) involvement among the patients over time. A large proportion of the patients (93%) were taking steroids and 24% of the patients required treatment with cyclophosphamide. Disease damage was common, with 28% of the patients having a Systemic Lupus International Collaborating Clinics/ACR damage score of >=1. CONCLUSION: The data on these patients from the UK JSLE Cohort Study, comprising one of the largest national inception cohorts of patients with juvenile SLE to date, indicate that severe organ involvement and significant disease activity are primary characteristics in children with juvenile SLE. In addition, accumulation of disease-associated damage could be seen. PMID- 22294382 TI - Characterization of the chromosomal translocation t(10;17)(q22;p13) in clear cell sarcoma of kidney. AB - Clear cell sarcoma of kidney (CCSK) is classified as a tumour of unfavourable histology by the National Wilms' Tumor Study Group. It has worse clinical outcomes than Wilms' tumour. Virtually nothing is known about CCSK biology, as there have been very few genetic aberrations identified to act as pointers in this cancer. Three cases of CCSK bearing a chromosomal translocation, t(10;17)(q22;p13), have been individually reported but not further investigated to date. The aim of this research was to characterize t(10;17)(q22;p13) in CCSK to identify the genes involved in the translocation breakpoints. Using fluorescently labelled bacterial artificial chromosomes (BACs) and a chromosome walking strategy on an index case of CCSK with t(10;17)(q22;p13) by karyotype, we identified the chromosomal breakpoints on 17p13.3 and 10q22.3. The translocation results in rearrangement of YWHAE on chromosome 17 and FAM22 on chromosome 10, producing an in-frame fusion transcript of ~3 kb, incorporating exons 1-5 of YWHAE and exons 2-7 of FAM22, as determined by RT-PCR using YWHAE- and FAM22 specific primers. The YWHAE-FAM22 transcript was detected in six of 50 further CCSKs tested, therefore showing an overall incidence of 12% in our cohort. No transcript-positive cases presented with stage I disease, despite this being the stage for 31% of our cohort. Tumour cellularity was significantly higher in the cases that were transcript-positive. Based on the chromosome 10 breakpoint identified by FISH and the sequences of the full-length transcripts obtained, the FAM22 members involved in the translocation in these CCSK cases include FAM22B and FAM22E. Elucidation of the role of YWHAE-FAM22 in CCSK will assist development of more efficient and targeted therapies for this childhood cancer, which currently has poor outcomes. PMID- 22294383 TI - Dense surface functionalization using peptides that recognize differences in organized structures of self-assembling nanomaterials. AB - We obtained novel peptides that selectively bind to self-assembling peptide nanomaterials from a random peptide library displayed on phages. Affinity dependent peptide screening gave phage clones displaying peptides with selective affinities against two kinds of highly networked nanofibers constructed of beta sheet peptides. Both peptide nanofibers have similar primary structures. Binding analyses of phage-displayed peptides by enzyme-linked immunosorbent assays demonstrated that the screened peptides specifically bind to the target nanofibers rather than to non-target nanofibers. Dot blot assays using chemically synthesized peptides revealed that one screened peptide with the sequence Thr-Tyr Leu-Pro-Trp-Pro-Ala has an affinity constant of 2.6 * 10(6) M(-1) against the target nanofibers. This affinity is 350 times greater than its affinity for non target nanofibers and 90 times greater than its affinity for mixed nanofibers that contain 50% target nanofibers. These results suggest that this screened peptide can recognize organized fine-structures. Surface modification of the peptide nanofibers with the screened peptide demonstrated that the peptide specifically binds to discrete binding sites on the target nanofibers. Cell adhesion assays on the nanofibers by means of RGDS-conjugated screened peptides showed that the number of adhered cells is largely dependent on the amount of bound RGDS-peptide. These results suggest that screened peptides can recognize the organization of self-assembled peptide nanomaterials, and that the conjugation of functional groups to the peptides can be used to functionalize the target nanomaterials. Furthermore, simultaneous use of individual specific peptides that have specificities for nanomaterials can generate highly dense functionalized self-assembling peptide nanomaterials. PMID- 22294384 TI - Comparison of computed tomography and magnetic resonance imaging for evaluation of cholesteatoma with labyrinthine fistulae. AB - OBJECTIVES/HYPOTHESIS: To compare preoperative computed tomography (CT) and magnetic resonance imaging (MRI) findings to the clinical features in patients with middle ear cholesteatoma with labyrinthine fistulae. STUDY DESIGN: Retrospective case series. METHODS: Twenty-eight patients who underwent surgery for middle ear cholesteatoma with one or more labyrinthine fistulae confirmed by CT were studied. Preoperative imaging analysis was performed using three dimensional fluid-attenuated inversion recovery (3D-FLAIR) MRI. Fistula size measured by CT and the signal intensity ratio (SIR) between the affected lesion in the inner ear and the cerebellum measured by 3D-FLAIR MRI were evaluated with respect to the clinical features and surgical findings. RESULTS: The SIR was not correlated with fistula size. The hearing threshold determined by preoperative bone conduction correlated with the SIR, especially in patients with acute sensorineural hearing loss, but it did not correlate with fistula size. Patients with fistula symptoms had a significantly higher SIR than those without symptoms, and similar findings were observed in patients with an active infection. Patients with a larger fistula or higher SIR tended to have a deeper fistula and a more adhesive fistula matrix at operation. CONCLUSIONS: SIR was more strongly correlated than CT findings to the clinical status of patients with labyrinthine fistulae caused by cholesteatoma. Adhesion of the cholesteatoma matrix to the membranous labyrinth correlated with the SIR; thus, SIR may accurately reflect the extent of inner ear dysfunction with a labyrinthine fistula. PMID- 22294385 TI - Therapeutic misconception, misestimation, and optimism in participants enrolled in phase 1 trials. AB - BACKGROUND: Ethical concerns about phase 1 trials persist. Important conceptual advances have been made in understanding concepts used to describe misunderstanding. However, a systematic, empirical evaluation of the frequency of misunderstanding incorporating recent developments is lacking. METHODS: The authors queried 95 participants in phase 1 trials to provide a more sophisticated estimate of the proportion who had therapeutic misconception (TM), defined as misunderstanding the research purpose or how research differs from individualized care, and therapeutic misestimation (TMis), defined as incorrectly estimating the chance of a research trial benefit as >20% or underestimating risk as 0%. RESULTS: Sixty-five of 95 respondents (68.4%) had TM, which was associated in a multivariate analysis with lower education and family income (P = .008 and P = .001, respectively), but TM was not associated with the vulnerability of having hardly any treatment options. Eighty-nine of 95 respondents (94%) had TMis, although only 18% reported this was a factual estimate. Although the risks of investigational agents and those exacerbated by research, such as uncertain outcomes, were mentioned (39% and 41% of respondents, respectively), risks novel to research, such as research biopsies, were rarely mentioned (3% of respondents). Although most of these respondents believed that their chance of benefit was greater and that their risk was lower than the population chance (optimists) (54.6%), a substantial minority of respondents (37.6%) were pessimists. CONCLUSIONS: TM continues to be prevalent. Estimates of personal benefit were not usually meant to report facts, it remains unknown whether respondents in the current study had TMis. Although they are not more vulnerable, phase 1 participants need improved understanding of key TM concepts, with attention to risks that are not present in standard of care. PMID- 22294386 TI - Hyperpolarized 129Xe gas lung MRI-SNR and T2* comparisons at 1.5 T and 3 T. AB - In this study, the signal-to-noise ratio of hyperpolarized (129)Xe human lung magnetic resonance imaging was compared at 1.5 T and 3 T. Experiments were performed at both B(0) fields with quadrature double Helmholtz transmit-receive chest coils of the same geometry with the same subject loads. Differences in sensitivity between the two field strengths were assessed from the signal-to noise ratio of multi-slice 2D (129)Xe ventilation lung images obtained at the two field strengths with a spatial resolution of 15 mm * 4 mm * 4 mm. There was a systematically higher signal-to-noise ratio observed at 3 T than at 1.5 T by a factor of 1.25. Mean image signal-to-noise ratio was in the range 27-44 at 1.5 T and 36-51 at 3 T. T 2* of (129)Xe gas in the partially inflated lungs was measured to be 25 ms and 18 ms at 1.5 T and 3 T, respectively. T 2* of (129)Xe gas in fully inflated lungs was measured to be 52 ms and 24 ms at 1.5 T and 3 T, respectively. PMID- 22294387 TI - Antioxidant activity of Moringa oleifera tissue extracts. AB - Moringa oleifera is an important source of antioxidants, tools in nutritional biochemistry that could be beneficial for human health; the leaves and flowers are used by the population with great nutritional importance. This work investigates the antioxidant activity of M. oleifera ethanolic (E1) and saline (E2) extracts from flowers (a), inflorescence rachis (b), seeds (c), leaf tissue (d), leaf rachis (e) and fundamental tissues of stem (f). The radical scavenging capacity (RSC) of extracts was determined using dot-blots on thin layer chromatography stained with a 0.4 mM 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) solution; spectrophotometric assays were recorded (515 nm). Antioxidant components were detected in all E1 and E2 from a, b and d. The best RSC was obtained with E1d; the antioxidants present in E2 reacted very slowly with DPPH. The chromatogram revealed by diphenylborinate-2-ethylamine methanolic solution showed that the ethanolic extract from the flowers, inflorescence rachis, fundamental tissue of stem and leaf tissue contained at least three flavonoids; the saline extract from the flowers and leaf tissue revealed at least two flavonoids. In conclusion, M. oleifera ethanolic and saline extracts contain antioxidants that support the use of the plant tissues as food sources. PMID- 22294388 TI - Role of hydrocarbon radicals CH(x) (x=1, 2, 3) in graphene growth: a theoretical perspective. AB - Many outstanding properties of graphene are blocked by the existence of structural defects. Herein, we propose an important healing mechanism for the growth of graphene, which is produced via plasma-enhanced chemical vapor decomposition (PECVD), that is, the healing of graphene with single vacancies by decomposed CH(4) (hydrocarbon radical CH(x), x=1, 2, 3). The healing processes undergo three evolutionary steps: 1) the chemisorption of the hydrocarbon radicals, 2) the incorporation of the C atom of the hydrocarbon radicals into the defective graphene, accompanied by the adsorption of the leaving H atom on the graphene surface, 3) the removal of the adsorbed H atom and H(2) molecule to generate the perfect graphene. The overall healing processes are barrierless, with a huge released heat of 530.79, 290.67, and 159.04 kcal mol(-1), respectively, indicative of the easy healing of graphene with single vacancies by hydrocarbon radicals. Therefore, the good performance of the PECVD method for the generation of graphene might be ascribed to the dual role of the CH(x) (x=1, 2, 3) species, acting both as carbon source and as defect healer. PMID- 22294389 TI - High-throughput screening for cellobiose dehydrogenases by Prussian Blue in situ formation. AB - Extracellular fungal flavocytochrome cellobiose dehydrogenase (CDH) is a promising enzyme for both bioelectronics and lignocellulose bioconversion. A selective high-throughput screening assay for CDH in the presence of various fungal oxidoreductases was developed. It is based on Prussian Blue (PB) in situ formation in the presence of cellobiose (<0.25 mM), ferric acetate, and ferricyanide. CDH induces PB formation via both reduction of ferricyanide to ferrocyanide reacting with an excess of Fe3+ (pathway 1) and reduction of ferric ions to Fe2+ reacting with the excess of ferricyanide (pathway 2). Basidiomycetous and ascomycetous CDH formed PB optimally at pH 3.5 and 4.5, respectively. In contrast to the holoenzyme CDH, its FAD-containing dehydrogenase domain lacking the cytochrome domain formed PB only via pathway 1 and was less active than the parent enzyme. The assay can be applied on active growing cultures on agar plates or on fungal culture supernatants in 96-well plates under aerobic conditions. Neither other carbohydrate oxidoreductases (pyranose dehydrogenase, FAD-dependent glucose dehydrogenase, glucose oxidase) nor laccase interfered with CDH activity in this assay. Applicability of the developed assay for the selection of new ascomycetous CDH producers as well as possibility of the controlled synthesis of new PB nanocomposites by CDH are discussed. PMID- 22294390 TI - Macromolecular synthesis and membrane perturbation assays for mechanisms of action studies of antimicrobial agents. AB - The definition and confirmation of the mechanism of action of an NCE is central to antimicrobial drug discovery. Most antibiotics currently in clinical use selectively target and block one or more bacterial macromolecular synthesis processes, e.g., DNA replication, RNA synthesis (transcription), protein synthesis (translation), cell wall (peptidoglycan) synthesis, and fatty acid (lipid) biosynthesis. This unit includes two protocols for determining the effect of test compounds on macromolecular synthesis, one in test tube format and the other in 96-well plate format. A membrane potential depolarization protocol is also provided. Disruption of cell membrane integrity may be a legitimate mechanism of action for antibacterials, but it also may be the result of nonspecific cell membrane activity, an effect that must be ruled out for mammalian cells. These assays provide useful means for verifying inhibition of an intended target pathway with investigational antimicrobial compounds. They can also be used as valuable secondary assays for lead optimization to eliminate inhibitors that display nonselective toxicity. PMID- 22294391 TI - Genetically engineered mouse models of ovarian cancer and their utility in drug discovery. AB - Ovarian cancer is the fourth most common cancer in women and the most lethal gynecological malignancy. The high mortality rate is attributable to the asymptomatic nature of the early stage of the disease, the lack of reliable screening tests, and the development of drug resistance. Approximately 90% of ovarian cancers are thought to originate from the ovarian surface epithelia (OSE). Development of in vivo experimental models that accurately recapitulate genetic events that occur during human epithelial ovarian cancer (EOC) initiation and progression is crucial for a better understanding of EOC pathogenesis, identification of early disease markers, and development of more effective therapy. Historically, one of the most challenging problems in developing genetically engineered mouse models (GEMMs) of EOC has been the lack of tissue specific promoters that regulate transgene expression exclusively in adult OSE cells. Recent improvements in gene delivery technology have greatly accelerated development of GEMMs of EOC. This unit describes two distinct methods of transforming OSE cells in GEMMs and the potential applications of these models in oncology drug discovery and development. PMID- 22294392 TI - Xenograft and transgenic mouse models of epithelial ovarian cancer and non invasive imaging modalities to monitor ovarian tumor growth in situ: applications in evaluating novel therapeutic agents. AB - Epithelial ovarian cancer (EOC) is the most commonly fatal gynecologic malignancy in developed countries. Most EOC patients are diagnosed at an advanced stage when disease has spread beyond the ovary. While many patients initially respond to surgery and chemotherapy, the long-term prognosis is generally unfavorable, with recurrence and development of drug-resistant disease. There is a critical need to identify new therapeutic agents that prolong disease-free intervals and effectively manage recurrent disease. Murine models of ovarian carcinoma are excellent models to study tumor biology in the search for new treatments for EOC. Described in this unit are methods for establishing xenograft or allograft models of EOC using ovarian carcinoma cell lines, in vivo imaging strategies for detection and quantification of EOC in transgenic and in xenograft/allograft models, and procedures for necropsy and pathological evaluation of experimental animals. PMID- 22294393 TI - Pre-clinical models of renal carcinoma and their utility in drug development. AB - Significant progress has been made in the treatment of patients with advanced renal cancer. In addition to immunotherapy, there are several potentially distinct therapeutic approaches for targeting molecular pathways. The murine models detailed in this unit are useful for testing rational combination strategies. Moreover, animal models contribute immensely to the understanding of the genetic, epigenetic, and biological aspects of human disease. Compared to humans, rodent models are relatively short-lived and allow for the facile study of clinically relevant pathologies. Animal models for the study of renal cell carcinoma (RCC) are particularly useful for the development of new drugs for kidney cancer. Included in this unit are several in vivo models that are currently used to evaluate therapeutic approaches to renal cancer therapy and to investigate the pathophysiology of this condition. Included are both murine (RENCA) and renal cell carcinomas in subcutaneous and orthotopic models using tumor cell lines and human tumor tissue. PMID- 22294394 TI - 5-Hydroxytryptamine receptor assays. AB - 5-Hydroxytryptamine (5-HT) receptors, by virtue of their broad expression pattern in peripheral and central tissues, regulate diverse physiological and behavioral responses through the activation of fourteen molecularly distinct receptor subtypes. The tissue-specific distribution of these receptors confers specificity for the actions of serotonin and highlights the therapeutic potential of serotonin receptor modulators. To better assess this therapeutic potential, it is useful to characterize serotonergic agonists and antagonists in physiologically relevant organ systems. Provided in this unit are twelve tissue bath assays using vascular and smooth muscle tissues isolated from guinea-pig, rat, and rabbit. These tests make possible the analyses of compounds at nine serotonin receptor subtypes. PMID- 22294395 TI - P1 (adenosine) purinoceptor assays. AB - P1 purinoceptors, or adenosine (ADO) receptors, mediate the biological effects of the endogenous nucleoside, ADO and its analogs. ADO works through four receptor subtypes: A(1), A(2A), A(2B), and A(3). Isolated tissue assays used for the pharmacological characterization of ADO receptors based on functional responses are described in this unit. The guinea pig atrium, pig coronary artery, guinea pig aorta ,and mouse aorta have been used for the characterization of ADO receptor subtypes. PMID- 22294396 TI - Models of cardiovascular disease: measurement of arrhythmogenic/antiarrhythmic activity in the guinea pig. AB - The protocols described in this unit are used to assess the effects of new chemical entities on arrhythmias in the guinea pig. In the anesthetized guinea pig, arrhythmias are induced by a slow intravenous infusion of digoxin, which provokes extrasystoles, ventricular tachyarrhythmias, and ultimately cardiac arrest. Imipramine precipitates the occurrence of arrhythmias, whereas propranolol shows protection against them. PMID- 22294397 TI - Models of anxiety: stress-induced hyperthermia (SIH) in singly housed mice. AB - Described in this unit is the stress-induced hyperthermia (SIH) test in mice in a single-housed format. This protocol has proven reliable in detecting the anxiolytic properties of test compounds. In this test, SIH is quantified in singly housed mice using a rectal temperature measurement as the stressor. Rectal temperature is measured twice at a 10-min interval. Due to the stress experienced during the first temperature measurement, the temperature of the second measurement (T(2)) is ~0.8 degrees to 1.5 degrees C higher than that of the first (T(1)). This difference in temperature (DeltaT = T(2) - T(1)) is defined as the SIH response. The SIH response is reduced by different classes of anxiolytics. The SIH test is simple and robust, it does not require training of animals, and test compound effects on motor behavior, feeding, and nociception do not affect test outcome. Furthermore, it is one of few anxiety tests that focuses on the physiological component of anxiety. PMID- 22294398 TI - Acute seizure tests in epilepsy research: electroshock- and chemical-induced convulsions in the mouse. AB - Epilepsy is a common (50 million patients worldwide) neurological disorder characterized by seizures that are caused by episodic abnormal electrical activity in the brain. Animal models play an essential role in epilepsy research including the discovery and development of new antiepileptic drugs. Described in this unit are protocols for traditional acute tests in which seizures are induced by either an electrical stimulation or a convulsant agent in non-epileptic mice. Specifically, protocols for the following acute seizure tests are provided: the maximal electroshock induced test (MES), the maximal electroshock seizure threshold (MEST) test, the 6-Hz seizure test, the subcutaneous pentylenetetrazol (s.c. PTZ) seizure test, and the intravenous pentylenetetrazol (i.v. PTZ) seizure test. These tests can be used to characterize anticonvulsant and/or proconvulsant properties of compounds in mice. The MES, s.c. PTZ, and 6-Hz seizure tests represent the three most widely used animal tests in drug-screening programs. Although the parameters of these tests are optimized for mice, the same tests (except for the 6-Hz seizure test), with some modifications, can be used with rats. PMID- 22294399 TI - Models of cardiovascular disease: measurement of antihypertensive activity in the conscious rat (SHR, DOCA-salt, and Goldblatt hypertension models). AB - The protocols described in this unit are used to assess the effects of new chemical entities on hypertension in conscious rats. In the spontaneously hypertensive rat (SHR) model, the results obtained with the reference compounds clonidine, prazosin, propranolol, and captopril are provided for illustration. All compounds demonstrate antihypertensive activity, with captopril and prazosin being the least and the most active, respectively. In the deoxycorticosterone acetate (DOCA)-salt model in the rat, the test substance shown as an example (a potential endothelin ET(A)-receptor antagonist) prevents the development of hypertension in the first phase. However, the effects of treatment disappear in the very last phase of the study, suggesting the development of a malignant hypertension resistant to treatment in this model. In the Goldblatt hypertension rat model (renal artery stenosis), losartan prevents the development of hypertension. It does not modify the weight of the right and left kidneys but slightly reduces the degree of cardiac hypertrophy. PMID- 22294400 TI - Models of aspects of schizophrenia: behavioral sensitization induced by subchronic phencyclidine administration. AB - Presented in this unit is a protocol using subchronically administered phencyclidine (PCP) for establishing a behavioral sensitization model of aspects of schizophrenia. This model is validated using haloperidol and risperidone. The end-point of the assay is locomotor hyperactivity, which is induced by PCP challenge following subchronic treatment with this NMDA receptor antagonist. The antipsychotics haloperidol, risperidone, and quetiapine all reduce hyperactivity in a dose-dependent and selective manner. While the effects of other antipsychotics such as clozapine, olanzapine, and ziprasidone are similar to haloperidol, the interpretation of responses to them is often confounded by nonspecific effects during habituation. PMID- 22294401 TI - Chemically induced mouse models of colitis. AB - Crohn's disease (CD) and ulcerative colitis (UC), both of which are referred to as inflammatory bowel disease (IBD), are chronic inflammatory disorders of the gastrointestinal tract that have characteristic clinical, pathological, endoscopic, and radiologic features. Knowledge about the pathogenesis of IBD has dramatically increased in recent years based in part on the use of experimental models of IBD. Although none of these models exactly mimics the human disorder, they have proven to be useful for studying many important aspects of these conditions. Detailed in this unit is a description of the most commonly used chemically induced mouse models of IBD. These include trinitrobenzene sulfonic acid (TNBS), oxazolone, and acute or chronic dextran sodium sulfate (DSS) colitis models. PMID- 22294402 TI - Monocrotaline-induced pulmonary hypertension in Wistar rats. AB - Pulmonary arterial hypertension (PAH) is a debilitating and often fatal disease characterized by a progressive increase in pulmonary vascular resistance that leads to right ventricular failure. Described in this unit is an in vivo model of monocrotaline-induced pulmonary hypertension in rats that can be used to assess the effects of antihypertensive agents on pulmonary artery pressure and right ventricular hypertrophy. PMID- 22294403 TI - Overview of mouse models of inflammatory bowel disease and their use in drug discovery. AB - Inflammatory bowel disease (IBD), a condition that affects millions of individuals, encompasses two distinct conditions: Crohn's disease (CD) and ulcerative colitis (UC). CD is an inflammatory condition affecting any part of the digestive tract between the mouth and anus, but, most commonly, the ileum and colon. It is distinguished by the presence of granulomas in the mucosal tissue and patchy areas of transmural inflammation. UC is restricted to the colon and is manifest as continuous inflammation starting from the rectum and extending back towards the cecum. Inflammation in UC is primarily restricted to mucosal layers. Research is ongoing to understand the causality of these two diseases, and advances in understanding of their pathology have resulted from the variety of mouse models of IBD that have emerged since the early 1990s. Described in this unit are contemporary mouse models of these conditions and examples of their use in drug discovery. PMID- 22294404 TI - Methods of inducing inflammatory bowel disease in mice. AB - Animal models of experimentally induced inflammatory bowel disease (IBD) are useful for understanding more about the mechanistic basis of disease, identifying new targets for therapeutic intervention, and testing novel therapeutic agents. This unit provides detailed protocols for four of the most commonly used mouse models of experimentally induced intestinal inflammation: chemical induction of colitis by dextran sodium sulfate (DSS), hapten-induced colitis via 2,4,6 trinitrobenzene sulfonic acid (TNBS), Helicobacter-induced colitis in mdr1a(-/-) mice, and the CD4(+) CD45RB(hi) SCID transfer colitis model. PMID- 22294405 TI - Natural products as a foundation for drug discovery. AB - Natural products have provided chemical leads for the development of many drugs for diverse indications. While most U.S. pharmaceutical firms have reduced or eliminated their in-house natural product groups, there is a renewed interest in this source of new chemical entities. Many of the reasons for the past decline in popularity of natural products are being addressed by the development of new techniques for screening and production. The aim of this unit is to review current strategies and techniques that increase the value of natural products as a source for novel drug candidates. PMID- 22294406 TI - Overview of high-throughput screening. AB - High-throughput screening (HTS) is a key process used in drug discovery to identify hits from compound libraries that may become leads for medicinal chemistry optimization. This updated overview discusses the utilization of compound libraries, compounds derived from combinatorial and parallel synthesis campaigns and natural product sources; creation of mother and daughter plates; and compound storage, handling, and bar coding in HTS. The unit also presents an overview of established and emerging assay technologies (i.e., time-resolved fluorescence, fluorescence polarization, fluorescence-correlation spectroscopy, functional whole cell assays, and high-content assays) and their integration in automation hardware and IT systems. This revised unit provides updated descriptions of state-of-the-art instrumentation and technologies in this rapidly changing environment. The section on assay methodologies now also covers enzyme complementation assays and methods for high-throughput screening of ion channel activities. Finally, a section on criteria for assay robustness is included discussing the Z'-factor, which is now a widely accepted criterion for evaluation and validation of high throughput screening assays. PMID- 22294407 TI - [Agricultural activities and epidemiology of malaria in Soudano-Sahelian zone in Cameroon]. AB - We have comparatively studied the dynamics of malaria transmission in the villages of Mokolo-Douvar located in the rural area with traditional agriculture and Gounougou irrigated rice area, in 2004 August and November and 2006 May and October, to assess vectors biting habits, and malaria inoculation rate and malaria parasite prevalence in cohort of children from 0 to 15 years. Mosquitoes were collected by landing catches on volunteers and by pyrethrum spray collections. A total of 5961 Anopheles were collected. Seven Anopheles species were identified: Anopheles gambiae s.s., Anopheles arabiensis, Anopheles funestus, Anopheles pharoensis, Anopheles rufipes, Anopheles ziemanni and Anopheles squamosus. A. arabiensis was the major species (56.2%) and the main malaria vector in both study sites, followed by A. funestus (32.6%). Malaria transmission was high in the irrigated area of Gounougou (1.42 infection bites per man per night) whereas in the non-irrigated zone of Mokolo-Douvar, it was below detection level during the rainy season (0,245 ib/h/n). In Gounougou, a total of 655 children were examined. The mean plasmodic index was 21.1%. Our findings confirm that changes in irrigated rice agriculture influence malaria transmission dynamics, and call for control measures that are readily adapted to local eco-epidemiological settings. PMID- 22294408 TI - Predicting story goodness performance from cognitive measures following traumatic brain injury. AB - PURPOSE: This study examined the prediction of performance on measures of the Story Goodness Index (SGI; Le, Coelho, Mozeiko, & Grafman, 2011) from executive function (EF) and memory measures following traumatic brain injury (TBI). It was hypothesized that EF and memory measures would significantly predict SGI outcomes. METHOD: One hundred sixty-seven individuals with TBI participated in the study. Story retellings were analyzed using the SGI protocol. Three cognitive measures--Delis-Kaplan Executive Function System (D-KEFS; Delis, Kaplan, & Kramer, 2001) Sorting Test, Wechsler Memory Scale--Third Edition (WMS-III; Wechsler, 1997) Working Memory Primary Index (WMI), and WMS-III Immediate Memory Primary Index (IMI)--were entered into a multiple linear regression model for each discourse measure. Two sets of regression analyses were performed, the first with the Sorting Test as the first predictor and the second with it as the last. RESULTS: The first set of regression analyses identified the Sorting Test and IMI as the only significant predictors of performance on measures of the SGI. The second set identified all measures as significant predictors when evaluating each step of the regression function. CONCLUSION: The cognitive variables predicted performance on the SGI measures, although there were differences in the amount of explained variance. The results (a) suggest that storytelling ability draws on a number of underlying skills and (b) underscore the importance of using discrete cognitive tasks rather than broad cognitive indices to investigate the cognitive substrates of discourse. PMID- 22294409 TI - Constrained versus unconstrained intensive language therapy in two individuals with chronic, moderate-to-severe aphasia and apraxia of speech: behavioral and fMRI outcomes. AB - PURPOSE: This Phase I study investigated behavioral and functional MRI (fMRI) outcomes of 2 intensive treatment programs to improve naming in 2 participants with chronic moderate-to-severe aphasia with comorbid apraxia of speech (AOS). Constraint-induced aphasia therapy (CIAT; Pulvermuller et al., 2001) has demonstrated positive outcomes in some individuals with chronic aphasia. Whether constraint to the speech modality or treatment intensity is responsible for such gains is still under investigation. Moreover, it remains to be seen whether CIAT is effective in individuals with persistent severe nonfluent speech and/or AOS. METHOD: A single-subject multiple-baseline approach was used. Both participants were treated simultaneously, first with Promoting Aphasics' Communicative Effectiveness (PACE; Davis & Wilcox, 1985) and then with CIAT. Pre-/posttreatment testing included an overt naming fMRI protocol. Treatment effect sizes were calculated for changes in probe accuracy from baseline to posttreatment phases and maintenance where available. RESULTS: Both participants made more and faster gains in naming following CIAT. Treatment-induced changes in BOLD activation suggested that better naming was correlated with the recruitment of perilesional tissue. CONCLUSION: Participants produced more target words accurately following CIAT than following PACE. Behavioral and fMRI results support the notion that the intense and repetitive nature of obligatory speech production in CIAT has a positive effect on word retrieval, even in participants with chronic moderate-to severe aphasia with comorbid AOS. PMID- 22294410 TI - A comparison of intention and pantomime gesture treatment for noun retrieval in people with aphasia. AB - PURPOSE: The effects of intention gesture treatment (IGT) and pantomime gesture treatment (PGT) on word retrieval were compared in people with aphasia. METHOD: Four individuals with aphasia and word retrieval impairments subsequent to left hemisphere stroke participated in a single-participant crossover treatment design. Each participant viewed target nouns on a computer screen in 2 counterbalanced training phases. Training included paired verbal + gesture treatment strategies to elicit verbal and/or gestural productions of target nouns. Treatment effects were measured using daily picture-naming probes for verbal naming and gesture productions for trained and untrained words as well as pre-/posttreatment standardized aphasia tests. Outcomes and Results IGT resulted in immediate effects on the verbal productions of 2 participants but lacked carryover to untrained words. PGT resulted in improved verbal production for 2 participants and immediate effects on the gesture productions of 3 participants, with carryover of gesture production to untrained words in 1 participant. Improvements on standardized aphasia tests were evident in 2 participants. CONCLUSION: IGT and PGT had positive treatment effects, but for contrasting communication modalities. Two individuals with mild-moderate aphasia improved verbal production with both IGT and PGT, and 2 individuals with severe aphasia improved gesture use with PGT. PMID- 22294411 TI - Effects of word frequency and modality on sentence comprehension impairments in people with aphasia. AB - PURPOSE: It is well known that people with aphasia have sentence comprehension impairments. The present study investigated whether lexical factors contribute to sentence comprehension impairments in both the auditory and written modalities using online measures of sentence processing. METHOD: People with aphasia and non brain-damaged controls participated in the experiment (n = 8 per group). Twenty one sentence pairs containing high- and low-frequency words were presented in self-paced listening and reading tasks. The sentences were syntactically simple and differed only in the critical words. The dependent variables were response times for critical segments of the sentence and accuracy on the comprehension questions. RESULTS: The results showed that word frequency influences performance on measures of sentence comprehension in people with aphasia. The accuracy data on the comprehension questions suggested that people with aphasia have more difficulty understanding sentences containing low-frequency words in the written compared to auditory modality. Both group and single-case analyses of the response time data also indicated that people with aphasia experience more difficulty with reading than listening. CONCLUSION: Sentence comprehension in people with aphasia is influenced by word frequency and presentation modality. PMID- 22294412 TI - Short-form Philadelphia naming test: rationale and empirical evaluation. AB - PURPOSE: To create two matched short forms of the Philadelphia Naming Test (PNT; Roach, Schwartz, Martin, Grewal, & Brecher, 1996) that yield similar results to the PNT for measuring anomia. METHOD: In Study 1, archived naming data from 94 individuals with aphasia were used to identify which PNT items should be included in the short forms. The 2 constructed sets of 30 items, PNT30-A and PNT30-B, were validated using archived data from a separate group of 56 individuals with aphasia. In Study 2, the reliability of the PNT, PNT30-A, and PNT30-B across independent test administrations was evaluated with a new group of 25 individuals with aphasia who were selected to represent the full range of naming impairment. RESULTS: In Study 1, PNT30-A and PNT30-B were found to be internally consistent, and accuracy scores on these subsets of items were highly correlated with the full PNT. In Study 2, PNT accuracy was extremely reliable over the span of 1 week, and independent administrations of PNT30-A and PNT30-B produced similar results to the PNT and to each other. CONCLUSION: The short forms of the PNT can be used to reliably estimate PNT performance, and the results can be compared to the provided norms. The 2 matched tests allow for the measurement of change in an individual's naming ability. PMID- 22294413 TI - Collagenous colitis-like condition in immunosuppressed infant baboons. AB - BACKGROUND: Collagenous colitis is a chronic inflammatory bowel disease of unknown etiology. It is fairly common in adult humans, but rare in infants, and has been associated with autoimmune disorders. METHODS: We report four infant baboons (age 7-12 months) that had received a transplant at 3 months of age and subsequent immunosuppressive therapy for periods of 4-10 months. All presented identical symptoms within a period of 4 weeks, including weight loss associated with chronic watery diarrhea that was unresponsive to standard antimicrobial treatment. RESULTS: Clinical chemistry evaluations were within normal ranges, viral causes were ruled out, and fecal and blood cultures were repeatedly negative. At necropsy, two infant baboons were found to have a form of collagenous colitis. In the remaining two baboons that had identical clinical features, immunosuppressive therapy was discontinued and treatment with budesonide was initiated. Both baboons recovered and remained well on no medication until the end of follow-up (24 months). CONCLUSIONS: Collagenous colitis has occasionally been reported in patients with organ transplants. It has been reported only once previously in baboons. The four cases reported here strongly suggest that 1) clinical features as well as histopathological findings of collagenous colitis in baboons are very similar to those in human patients; 2) it was associated with the immunocompromised state of the baboons, as two nonimmunosuppressed age-matched baboons in close proximity did not develop the condition; and 3) it may have had an infectious origin, as all four cases developed within a 4-week period of time. PMID- 22294414 TI - Venous oxygenation mapping using velocity-selective excitation and arterial nulling. AB - A new MRI technique to map the oxygenation of venous blood is presented. The method uses velocity-selective excitation and arterial nulling pulses, combined with phase sensitive signal detection to isolate the venous blood signal. T2 of this signal along with a T2-Y calibration curve yields estimates of venous oxygenation in situ. Results from phantoms and healthy human subjects under normoxic and hypoxic conditions are shown, and venous saturation levels estimated from both sagittal sinus and gray matter-based regions of interest are compared with the related techniques TRUST and QUIXOTIC. In addition, combined with an additional scan without arterial nulling pulses, the oxygen saturation level on arterial side can also be estimated. PMID- 22294415 TI - Dual regulation of metalloproteinase expression in chondrocytes by Wnt-1 inducible signaling pathway protein 3/CCN6. AB - OBJECTIVE: Wnt-1-inducible signaling pathway protein 3 (WISP-3)/CCN6 is mutated in progressive pseudorheumatoid dysplasia and may have effects on cartilage homeostasis. The aim of this study was to ascertain additional roles for WISP 3/CCN6 by determining its expression in osteoarthritic (OA) cartilage and by investigating its effects on cartilage-relevant metalloproteinase expression in immortalized (C-28/I2) and primary chondrocytes. METHODS: Cartilage steady-state levels of WISP-3/CCN6 messenger RNA and protein production were determined by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. WISP-3/CCN6 was overexpressed in C-28/I2 cells, and the resultant clones were analyzed by quantitative RT-PCR. The stable clones were analyzed by RT-PCR for metalloproteinase expression, and the signaling pathways involved were investigated using pharmacologic inhibition. The effects of WISP-3/CCN6 on metalloproteinase expression in primary chondrocytes were investigated using a small interfering RNA approach. RESULTS: WISP-3/CCN6 was highly expressed in OA cartilage compared with undamaged cartilage, at both the RNA and protein levels. WISP-3/CCN6 overexpression in C-28/I2 cells resulted in unexpected dual regulation of metalloproteinases; expression of the potent aggrecanase ADAMTS-5 was down-regulated 9-fold, while expression of MMP-10 was up regulated 14-fold, and these responses were accentuated in the WISP-3/CCN6 clones grown in suspension. MMP-10 up-regulation was dependent on several MAPKs, but WISP-3/CCN6-mediated ADAMTS-5 repression was independent of these pathways and was partially relieved by activation of beta-catenin signaling. WISP-3/CCN6 also suppressed ADAMTS-5 expression in C-28/I2 cells treated with cytokines. In cytokine-treated primary chondrocytes, gene silencing of WISP-3/CCN6 resulted in enhanced ADAMTS-5 expression, while MMP-10 expression was suppressed. CONCLUSION: WISP-3/CCN6 was highly expressed in end-stage OA cartilage, suggesting a role for this growth factor in cartilage homeostasis. WISP-3/CCN6-induced repression of ADAMTS-5 expression and regulation of MMP-10 expression suggest complex and context-dependent roles for WISP-3/CCN6 in cartilage biology. PMID- 22294417 TI - Brains and persons: an educational perspective. PMID- 22294416 TI - ROR2 is a novel prognostic biomarker and a potential therapeutic target in leiomyosarcoma and gastrointestinal stromal tumour. AB - Soft-tissue sarcomas are a group of malignant tumours whose clinical management is complicated by morphological heterogeneity, inadequate molecular markers and limited therapeutic options. Receptor tyrosine kinases (RTKs) have been shown to play important roles in cancer, both as therapeutic targets and as prognostic biomarkers. An initial screen of gene expression data for 48 RTKs in 148 sarcomas showed that ROR2 was expressed in a subset of leiomyosarcoma (LMS), gastrointestinal stromal tumour (GIST) and desmoid-type fibromatosis (DTF). This was further confirmed by immunohistochemistry (IHC) on 573 tissue samples from 59 sarcoma tumour types. Here we provide evidence that ROR2 expression plays a role in the invasive abilities of LMS and GIST cells in vitro. We also show that knockdown of ROR2 significantly reduces tumour mass in vivo using a xenotransplantation model of LMS. Lastly, we show that ROR2 expression, as measured by IHC, predicts poor clinical outcome in patients with LMS and GIST, although it was not independent of other clinico-pathological features in a multivariate analysis, and that ROR2 expression is maintained between primary tumours and their metastases. Together, these results show that ROR2 is a useful prognostic indicator in the clinical management of these soft-tissue sarcomas and may represent a novel therapeutic target. PMID- 22294418 TI - Salivary protein and solCD44 levels as a potential screening tool for early detection of head and neck squamous cell carcinoma. AB - BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a devastating disease usually diagnosed at a late stage when cure rates are 40%. We examined a simple and inexpensive molecular tool that may aid HNSCC detection. METHODS: Building on prior findings that total protein levels are elevated in 102 HNSCC cases versus 84 control subjects, we further analyzed these levels with respect to important risk and demographic variables and compared the results to soluble CD44 (solCD44). Using multivariate adaptive regression splines (MARSs)-logit modeling and logistic regression, we determined whether total protein, solCD44, or the combination best identifies HNSCC. RESULTS: Combined higher levels of solCD44 and protein were significantly associated with HNSCC (odds ratio [OR] = 24.90; 95% confidence interval [CI], 9.04-68.57; area under the curve [AUC] = 0.786). A model including protein plus solCD44 resulted in a better area (AUC 0.796) than either marker alone. CONCLUSION: Oral rinse levels of solCD44 and protein seem to hold promise for detection of HNSCC. PMID- 22294419 TI - Effects of cranberry extracts on growth and biofilm production of Escherichia coli and Staphylococcus species. AB - Biofilm producing bacteria such as Staphylococcus species and Escherichia coli are the most common cause of catheter related urinary tract infections (UTIs). The American cranberry (Vaccinium macrocarpon) is utilized widely as a prophylaxis for UTIs due to its prevention of microbial adhesion. Cranberry contains proanthocyanidins (PACs), which have been implicated as active constituents responsible for its bacterial antiadhesive properties. Despite overwhelming data supporting cranberry's beneficial effects against human pathogenic bacteria, there is limited information regarding its effects on biofilm formation. This study evaluated the effects of three proprietary PAC standardized cranberry extracts on the inhibition of bacterial growth and biofilm production against a panel of clinically relevant pathogens: Staphylococcus epidermidis, Staphylococcus aureus, clinical methicillin-resistant S. aureus (MRSA), Staphylococcus saprophyticus and Escherichia coli. The extracts inhibited the growth of the Gram-positive bacteria (Staphylococcus spp.) but not the Gram negative species (E. coli) with minimum inhibitory concentrations in the range 0.02-5 mg/mL. The extracts also inhibited biofilm production by the Gram-positive bacteria but did not eradicate their established biofilm. These results suggest that cranberry may have beneficial effects against the growth and biofilm producing capability of Gram-positive bacteria pathogens. PMID- 22294420 TI - Adenoid cystic carcinoma of the head and neck: Incidence and survival trends based on 1973-2007 Surveillance, Epidemiology, and End Results data. AB - BACKGROUND: Adenoid cystic carcinoma (ACC) of the head and neck (ACCHN) is a rare tumor of minor salivary, parotid, and submandibular glands. The biologic behavior of the disease is poorly understood, and nonsurgical treatment strategies have yet to be standardized. The long-term prognosis continues to be guarded, with an estimated 10-year survival of <60%. Population-based studies examining ACC are scarce. The authors aimed to analyze incidence rates and survival outcomes for patients diagnosed with ACCHN using national population-based data. METHODS: Data were obtained from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Newly diagnosed ACCHN cases reported to SEER from 1973 through 2007 were categorized according to their sex, race, age, year of diagnosis, marital status, treatment interventions, primary tumor site, and disease stage. Incidence of ACCHN and postdiagnosis survival were examined over time and compared across different demographic and disease-related categories. RESULTS: The authors identified 3026 patients with ACCHN. The mean age at diagnosis among those cases was 57.4 years (range, 11-99 years). Analyses of incidence data demonstrated a decline in ACCHN rates between 1973 and 2007, noted across all sexes and races with no detectable inflexion points. The overall 5 year, 10-year, and 15-year survival outcomes for ACCHN patients were 90.3%, 79.9%, and 69.2%, respectively. Females, patients with localized disease, and younger patients were found to have significantly better survival across all time periods (all comparison-specific log-rank P values <0.001). Multivariate analyses revealed better prognosis among women compared with men (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.65-0.82), among married compared with unmarried individuals (HR, 0.81; 95% CI, 0.71-0.91), with certain sites of origin and stage of disease (HR, 2.788; 95% CI, 2.36-3.29), and in those who had surgery of the primary tumor site (HR, 0.45; 95% CI, 0.37-0.54). CONCLUSIONS: The overall incidence of ACC is declining. The noted differences in survival based on sex, marital status, site of origin, and treatment intervention require further investigation. PMID- 22294421 TI - Fluorogenic peptide-based substrates for monitoring thrombin activity. AB - The synthesis of a series of peptides containing C-terminal 7-amino-4 methylcoumarin (AMC) for use in the thrombin generation test (TGT) is described. The lead structure in this project was H-Gly-Gly-Arg-AMC, of which the water solubility and kinetic parameters (K(M) and k(cat)) are greatly improved over those of the substrate in current use in the TGT: Cbz-Gly-Gly-Arg-AMC. A series of N-terminally substituted Gly-Gly-Arg-AMC derivatives were synthesized, as well as implementation of structural changes at either the P(2) or P(3) position of the peptide backbone. Furthermore, two substrates were synthesized that have structural similarities to the chromogenic thrombin substrate SQ68 or that contain a 1,2,3-triazole moiety in the peptide chain, mimicking an amide bond. To determine the applicability of newly synthesized fluorogenic substrates for monitoring continuous thrombin generation, the K(M) and k(cat) values of the conversion of these fluorogenic substrates by thrombin (FIIa) and factor Xa (FXa) were quantified. An initial selection was made on basis of these data, and suitable substrates were further evaluated as substrates in the thrombin generation assay. Assessment of the acquired data showed that several substrates, including the SQ68 derivative Et-malonate-Gly-Arg-AMC and N-functionalized Gly Gly-Arg-AMC derivatives, are suitable candidates for replacement of the substrate currently in use. PMID- 22294422 TI - [PHTLS team course: a pilot project. Structured student education in prehospital care of severely injured patients]. AB - BACKGROUND: The training of medical school students at the University of Heidelberg seems to be improvable regarding prehospital trauma treatment compared to an established anaesthesiology-based training for medical emergencies. This study addresses the current situation and possibilities for advancing this training. MATERIAL AND METHODS: A baseline was set by interviews of the medical school students. Based on this the hypothesis was postulated that there is a deficit in the education of the medical school students concerning the training in prehospital trauma treatment. This was proved by questionnaires given to the students in the 7th and 8th semesters at the University of Heidelberg Medical School. The results were evaluated and a possible approach for improvement was developed. RESULTS: A total of 111 questionnaires could be evaluated. It could be shown that the existing education was not effectual and that there is a need for a praxis-orientated 1-day course in prehospital trauma treatment. CONCLUSION: Especially the treatment of multiply injured patients is a challenge for young medical professionals. However, there is a high motivation to learn and train in emergency medicine. The students long for a practical trauma course compared to the advanced medical CPR course provided by the Department of Anaesthesiology of the University of Heidelberg. Those algorithm-based trauma courses do exist with PHTLS(r) and ATLS(r). Based on these courses we developed the PHTLS(r) TEAM course. PMID- 22294423 TI - The parachute design as a new extraperitoneal method of closing a recalcitrant high-output enterocutaneous fistula: report of a case. AB - We introduce a new method for closure of a recalcitrant high-output jejunal enterocutaneous fistula. First, a transposed rectus abdominis muscle is sutured into the fistula opening using a parachuting technique, then the muscle is covered with a skin graft and temporarily immobilized to the fistula wall and abdominal wall with a negative pressure device. This extraperitoneal method provides tension-free closure of the fistula with well-vascularized tissue, without compromising the intestinal lumen. No bowel is resected. This new technique allows for early mobilization and recommencement of enteral nutrition. PMID- 22294424 TI - Laparoscopic resection of a gastrointestinal stromal tumor of the rectum after treatment with imatinib mesylate: report of a case. AB - This report describes the laparoscopic resection of a rectal GIST after treatment with imatinib mesylate. A 56-year-old male presented with a submucosal tumor (longest diameter, 8 cm) arising in the lower rectum. A core needle biopsy revealed that the tumor contained bundles of spindle-like cells. Immunostaining revealed that the tumor was positive for c-kit and CD34. Analysis of the c-kit gene revealed a substitution of ACA (threonine) by GCA (alanine) at codon 574 of exon 11. Imatinib mesylate (400 mg/day) was given as preoperative adjuvant therapy for 3 months, and the tumor shrank to 5 cm in diameter. Proctectomy with transanal anastomosis could be performed laparoscopically, while preserving the anus. There was no evidence of recurrence 2 years 6 months after surgery. Preoperative adjuvant chemotherapy with imatinib mesylate may permit the use of less invasive treatment procedures, allowing anal preservation. PMID- 22294425 TI - Incremental value of magnetic resonance imaging for breast surgery planning. AB - PURPOSE: The aim of this study was to evaluate the effect of breast magnetic resonance imaging (MRI) on preoperative or intraoperative surgical planning. METHODS: One hundred and sixty females with breast cancer were enrolled in the study. The contribution of MRI compared to MMG and USG, their histopathological concordance, and their impact on surgical treatment were evaluated prospectively. RESULTS: In 48 (30.0%) of the patients, MRI identified suspicious lesions that were not detected by MMG and USG. The diagnosis by MRI was accurate in 17 (10.6%) of them, while in remaining 31 patients (19.4%) the additional lesions found by MRI and interpreted as malignant were found not to be malignant. The pathological accordance of MRI and MMG compared with USG were 69.3 and 70.0%, respectively, whereas individually, MMG and USG were in accordance with the pathological examination in 52.9 and 67.9% of the cases, respectively. CONCLUSIONS: Assessment of the tumor size, multifocality, multicentricity, and presence of ductal carcinoma in situ by MRI may lead to misinterpretations in the majority of patients. The surgical approach should not be changed based solely on MRI findings. An accurately interpreted MMG combined with USG may be sufficient in most cases. PMID- 22294426 TI - Burkitt's lymphoma of an ileal pouch following restorative proctocolectomy. PMID- 22294427 TI - Decreased intrinsic brain connectivity is associated with reduced clinical pain in fibromyalgia. AB - OBJECTIVE: A major impediment to the development of novel treatment strategies for fibromyalgia (FM) is the lack of an objective marker that reflects spontaneously reported clinical pain in patients with FM. Studies of resting state intrinsic brain connectivity in FM have demonstrated increased insular connectivity to the default mode network (DMN), a network whose activity is increased during nontask states. Moreover, increased insular connectivity to the DMN was associated with increased spontaneous pain levels. However, as these analyses were cross-sectional in nature, they provided no insight into dynamic changes in connectivity or their relationship to variations in self-reported clinical pain. The purpose of this study was to evaluate longitudinal changes in the intrinsic brain connectivity of FM patients treated with nonpharmacologic interventions known to modulate pain levels in this patient population, and to test the hypothesis that the reduction of DMN-insula connectivity following therapy would correlate with diminished pain. METHODS: Seventeen FM patients underwent resting-state functional magnetic resonance imaging at baseline and following 4 weeks of a nonpharmacologic intervention to diminish pain. Intrinsic DMN connectivity was evaluated using probabilistic independent components analysis. Longitudinal changes in intrinsic DMN connectivity were evaluated by paired analysis, and correlations between longitudinal changes in clinical pain and changes in intrinsic DMN connectivity were investigated by multiple linear regression analysis. Changes in clinical pain were assessed with the short form of the McGill Pain Questionnaire (SF-MPQ). RESULTS: Clinical pain as assessed using the sensory scale of the SF-MPQ was reduced following therapy (P=0.02). Intrinsic DMN connectivity to the insula was reduced, and this reduction correlated with reductions in pain (corrected P<0.05). CONCLUSION: Our findings suggest that intrinsic brain connectivity can be used as a candidate objective marker that reflects changes in spontaneous chronic pain within individual FM patients. We propose that intrinsic connectivity measures could potentially be used in either research or clinical settings as a complementary, more objective outcome measure for use in FM. PMID- 22294428 TI - Flip angle profile correction for T1 and T2 quantification with look-locker inversion recovery 2D steady-state free precession imaging. AB - Fast methods using balanced steady-state free precession have been developed to reduce the scan time of T1 and T2 mapping. However, flip angle (FA) profiles created by the short radiofrequency pulses used in steady-state free precession deviate substantially from the ideal rectangular profile, causing T1 and T2 mapping errors. The purpose of this study was to develop a FA profile correction for T1 and T2 mapping with Look-Locker 2D inversion recovery steady-state free precession and to validate this method using 2D spin echo as a reference standard. Phantom studies showed consistent improvement in T1 and T2 accuracy using profile correction at multiple FAs. Over six human calves, profile correction provided muscle T1 estimates with mean error ranging from excellent ( 0.6%) at repetition time/FA = 18 ms/60 degrees to acceptable (6.8%) at repetition time/FA = 4.9 ms/30 degrees , while muscle T2 estimates were less accurate with mean errors of 31.2% and 47.9%, respectively. PMID- 22294429 TI - Visualising the invisible: a network approach to reveal the informal social side of student learning. AB - World-wide, universities in health sciences have transformed their curriculum to include collaborative learning and facilitate the students' learning process. Interaction has been acknowledged to be the synergistic element in this learning context. However, students spend the majority of their time outside their classroom and interaction does not stop outside the classroom. Therefore we studied how informal social interaction influences student learning. Moreover, to explore what really matters in the students learning process, a model was tested how the generally known important constructs-prior performance, motivation and social integration-relate to informal social interaction and student learning. 301 undergraduate medical students participated in this cross-sectional quantitative study. Informal social interaction was assessed using self-reported surveys following the network approach. Students' individual motivation, social integration and prior performance were assessed by the Academic Motivation Scale, the College Adaption Questionnaire and students' GPA respectively. A factual knowledge test represented student' learning. All social networks were positively associated with student learning significantly: friendships (beta = 0.11), providing information to other students (beta = 0.16), receiving information from other students (beta = 0.25). Structural equation modelling revealed a model in which social networks increased student learning (r = 0.43), followed by prior performance (r = 0.31). In contrast to prior literature, students' academic motivation and social integration were not associated with students' learning. Students' informal social interaction is strongly associated with students' learning. These findings underline the need to change our focus from the formal context (classroom) to the informal context to optimize student learning and deliver modern medics. PMID- 22294430 TI - Helicobacter pylori infection and colorectal cancer risk: evidence from a large population-based case-control study in Germany. AB - Evidence concerning the role of Helicobacter pylori infection in the development of colorectal cancer remains controversial. The authors assessed the association of H. pylori seroprevalence with risk of colorectal cancer in a large population based case-control study from Germany in 2003-2007. Serum antibodies to H. pylori in general and the cytotoxin-associated gene A protein (CagA) were measured in 1,712 incident colorectal cancer cases and 1,669 controls. The association between H. pylori seroprevalence and colorectal cancer risk was estimated by logistic regression, with adjustment for potential confounders and stratification by age group, sex, anatomic subsites, and cancer stage. Overall, H. pylori seroprevalence was higher in cases (46.1%) than in controls (40.1%), resulting in an age- and sex-adjusted odds ratio of 1.30 (95% confidence interval (CI): 1.14, 1.50). Adjustment for established colorectal cancer risk factors decreased the odds ratio to 1.26 (95% CI: 1.09, 1.47), with a further reduction to 1.18 (95% CI: 1.01, 1.38) after additional adjustment for previous colorectal endoscopy. Stratified analyses showed risk elevation to be essentially confined to left sided colorectal cancer, with an odds ratio of 1.22 (95% CI: 1.02, 1.45), suggesting that H. pylori infection may be associated with a small yet relevant risk increase in the left colorectum. PMID- 22294431 TI - Pericardiocentesis: a clinical anatomy review. AB - The safe and successful performance of pericardiocentesis demands a working and specific knowledge of anatomy. Misunderstanding of anatomy may result in failure or serious complications. This review attempts to aid understanding of the anatomical framework, pitfalls, and complications of pericardiocentesis. Pericardiocentesis is carried out for aspiration of blood from the pericardial cavity in cases of cardiac tamponade and symptomatic pericardial effusion. In addition, this technique may be used for the diagnosis of neoplastic effusions, purulent pericarditis, and introduction of cytotoxic agents into the pericardial space. Most complications of the procedure are due to the needle penetrating the heart and surrounding structures such a coronary arteries, lungs, stomach, colon, and liver. These complications, if severe, may result in pneumothorax, hemothorax, arrhythmias, infections or arterial bleeding. Therefore, the more fluid or blood there is between the myocardium and pericardium--within the pericardial cavity--the less chance of complications. With a thorough knowledge of the complications, regional anatomy and rationale of the technique, and adequate experience, a pericardiocentesis can be carried out safely and successfully. PMID- 22294432 TI - Fermentation of xylose to succinate by enhancement of ATP supply in metabolically engineered Escherichia coli. AB - In Escherichia coli K12, succinate was not the dominant fermentation product from xylose. To reduce byproduct formation and increase succinate accumulation,pyruvate formate lyase and lactate dehydrogenase, encoded by pflB and ldhA genes, were inactivated. However, these mutations eliminated cell growth and xylose utilization. During anaerobic growth of bacteria, organic intermediates,such as pyruvate, serve as electron acceptors to maintain the overall redox balance. Under these conditions, the ATP needed for cell growth is derived from substrate level phosphorylation. In E. coli K12, conversion of xylose to pyruvate only yielded 0.67 net ATP per xylose during anaerobic fermentation. However, E. coli produces equimolar amounts of acetate and ethanol from two pyruvates, and these reactions generate one additional ATP. Conversion of xylose to acetate and ethanol increases the net ATP yield from 0.67 to 1.5 per xylose, which could meet the ATP needed for xylose metabolism. A pflB deletion strain cannot convert pyruvate to acetyl coenzyme A, the precursor for acetate and ethanol production, and could not produce the additional ATP. Thus,the double mutations eliminated cell growth and xylose utilization. To supply the sufficient ATPs, overexpression of ATP-forming phosphoenolpyruvate-carboxykinase from Bacillus subtilis 168 in an ldhA, pflB, and ppc deletion strain resulted in a significant increase in cell mass and succinate production. In addition, fermentation of corn stalk hydrolysate containing a high percentage of xylose and glucose produced a final succinate concentration of 11.13 g l-1 with a yield of1.02 g g-1 total sugars during anaerobic fermentation. PMID- 22294433 TI - The short form of the recombinant CAL-A-type lipase UM03410 from the smut fungus Ustilago maydis exhibits an inherent trans-fatty acid selectivity. AB - The Ustilago maydis lipase UM03410 belongs to the mostly unexplored Candida antarctica lipase (CAL-A) subfamily. The two lipases with [corrected] the highest identity are a lipase from Sporisorium reilianum and the prototypic CAL-A. In contrast to the other CAL-A-type lipases, this hypothetical U. maydis lipase is annotated to possess a prolonged N-terminus of unknown function. Here, we show for the first time the recombinant expression of two versions of lipase UM03410: the full-length form (lipUMf) and an Nterminally truncated form (lipUMs). For comparison to the prototype, the expression of recombinant CAL-A in E. coli was investigated. Although both forms of lipase UM03410 could be expressed functionally in E. coli, the N-terminally truncated form (lipUMs) demonstrated significantly higher activities towards p-nitrophenyl esters. The functional expression of the N-terminally truncated lipase was further optimized by the appropriate choice of the E. coli strain, lowering the cultivation temperature to 20 degrees C and enrichment of the cultivation medium with glucose. Primary characteristics of the recombinant lipase are its pH optimum in the range of 6.5 7.0 and its temperature optimum at 55 degrees C. As is typical for lipases, lipUM03410 shows preference for long chain fatty acid esters with myristic acid ester (C14:0 ester) being the most preferred one.More importantly, lipUMs exhibits an inherent preference for C18:1Delta9 trans and C18:1Delta11 trans fatty acid esters similar to CAL-A. Therefore, the short form of this U. maydis lipase is the only other currently known lipase with a distinct trans-fatty acid selectivity. PMID- 22294434 TI - Phylloid hypermelanosis in a child with psychomotor delay, cicatricial alopecia, hearing loss and polythelia. PMID- 22294435 TI - Allelic drop-out, allele imbalance, or loss of heterozygosity? PMID- 22294436 TI - Comparison of adverse events during 5-fluorouracil versus 5 fluorouracil/oxaliplatin adjuvant chemotherapy for stage III colon cancer: a population-based analysis. AB - BACKGROUND: In clinical trials, combined 5-fluorouracil (5FU) plus oxaliplatin improves the survival of patients who have resected, stage III colon cancer with manageable toxicity. However, the tolerability of this in the general population of patients with colon cancer is uncertain. METHODS: Adverse outcomes were compared in patients with stage III colon cancer who received either 5FU or 5FU/oxaliplatin within 120 days of undergoing resection versus a control group of patients with stage II colon cancer who did not receive chemotherapy in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and in data from the New York State Cancer Registry linked to Medicare and Medicaid. Hospitalizations, emergency room (ER) visits, and outpatient adverse events (AEs) were measured in claims from 30 days to 9 months after patients underwent resection. Multiple logistic regression was used to calculate adjusted odds ratios of events by treatment. Propensity score matching was used to minimize selection bias. RESULTS: Adverse outcomes were more frequent for chemotherapy recipients. AE rates were higher in patients who received 5FU/oxaliplatin (81%) compared with patients who received 5FU alone (72%), in the SEER-Medicare data. The effect of oxaliplatin on AEs was greater in older patients: The odds ratio was 2.10 (95% confidence interval, 1.53-2.87) for patients aged >= 75 years versus 1.75 (95% confidence interval, 1.39-2.21) for patients aged <75 years. ER use was high in Medicaid patients (83% of those who received chemotherapy), but neither ER use nor hospitalization was increased by oxaliplatin. The 60-day mortality rate was 1% to 3% for patients who received 5FU alone and 1% to 2% for patients who received combined 5FU/oxaliplatin. CONCLUSIONS: The incremental harms of adjuvant chemotherapy with 5FU/oxaliplatin versus 5FU alone were modest in patients with stage III colon cancer who were insured by Medicare and Medicaid. The additional harms in patients aged >= 75 years largely were restricted to outpatient events and did not extend to an increased rate of hospitalization or early death. PMID- 22294437 TI - Electrodeposition of pronectin for titanium to augment gingival epithelium adhesion. AB - This paper is one trial of surface modification of titanium with pronectin F+ (PN) of an artificial protein to enhance gingival adhesion. Titanium plates were electrodeposited in the PN solution to prepare PN-electrodeposited titanium plates. When PN detachment from the PN-electrodeposited titanium plates was investigated, no detachment was observed, in contrast to the case of titanium plates simply coated with PN. A cell culture experiment demonstrated that electrodeposited PN had an inherent ability to enhance the initial attachment of gingival epithelial cells. The PN-electrodeposited titanium plates were implanted between the gingival epithelium and the underlying bone tissue of rabbits to evaluate epithelial growth on the plates and their gingival adhesion. Non-treated and PN-coated titanium plates were used as controls. PN electrodeposition enhanced epithelial growth and adhesion of titanium plates to a significantly great extent compared with PN-coated plates. These findings demonstrate that PN electrodeposition is a promising method to enhance epithelium adhesion onto a titanium surface. PMID- 22294438 TI - Integrated genome and transcriptome sequencing identifies a novel form of hybrid and aggressive prostate cancer. AB - Next-generation sequencing is making sequence-based molecular pathology and personalized oncology viable. We selected an individual initially diagnosed with conventional but aggressive prostate adenocarcinoma and sequenced the genome and transcriptome from primary and metastatic tissues collected prior to hormone therapy. The histology-pathology and copy number profiles were remarkably homogeneous, yet it was possible to propose the quadrant of the prostate tumour that likely seeded the metastatic diaspora. Despite a homogeneous cell type, our transcriptome analysis revealed signatures of both luminal and neuroendocrine cell types. Remarkably, the repertoire of expressed but apparently private gene fusions, including C15orf21:MYC, recapitulated this biology. We hypothesize that the amplification and over-expression of the stem cell gene MSI2 may have contributed to the stable hybrid cellular identity. This hybrid luminal neuroendocrine tumour appears to represent a novel and highly aggressive case of prostate cancer with unique biological features and, conceivably, a propensity for rapid progression to castrate-resistance. Overall, this work highlights the importance of integrated analyses of genome, exome and transcriptome sequences for basic tumour biology, sequence-based molecular pathology and personalized oncology. PMID- 22294439 TI - 2012 ACCF/AATS/SCAI/STS expert consensus document on transcatheter aortic valve replacement: developed in collaboration with the American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Failure Society of America, Mended Hearts, Society of Cardiovascular Anesthesiologists, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance. PMID- 22294440 TI - Prevention of cytotoxicity of nickel by quercetin: the role of reactive oxygen species and histone acetylation. AB - Excessive exposure to nickel may cause health effects on the blood, lung, nose, kidney, reproductive system, skin and the unborn child. In the present study, we found that Ni2+ exposure led to a time- and dose-dependent proliferation arrest and death in human leukemia HL-60 cells. In the presence of 1 mM Ni2+, reactive oxygen species (ROS) generation (indicated by the level of malondialdehyde) increased to 323% and histone acetylation decreased to 32%. Interestingly, quercetin (QU) dose dependently prevented Ni2+-induced cell proliferation arrest and death from 0 to 80 MUM but showed similar activity of scavenging ROS at the concentrations of 20, 40 and 80 uM. When the effect of QU on histone acetylation was studied, QU significantly prevented Ni2+-induced histone hypoacetylation at 40 or 80 uM. Moreover, increase in histone acetylation by trichostatin A could also significantly enhance the protection effect of QU at 10 or 20 uM but not at higher concentrations. Thus, our results further confirmed the critical role of ROS and histone hypoacetylation in the cytotoxicity of Ni2+ exposure and proved that QU is a potentially useful native dietary compound to efficiently prevent Ni2+-caused cytotoxicity through both diminishing ROS generation and increasing histone acetylation. PMID- 22294441 TI - Aluminum phosphide-induced genetic and oxidative damages in rats: attenuation by Laurus nobilis leaf extract. AB - Aluminum phosphide (AlP) is a colorless, flammable, liquefied pesticide that is commonly used to control insects, nematodes, weeds, and pathogens in crops, forests, ornamental nurseries, and wood products. Early investigations of AlP poisoned mammalian cells led to the proposed involvement of oxidative damage in its toxicity mechanism. Therefore, this study was aimed to evaluate the effect of Laurus nobilis (L) leaf extract (LNE) against AlP-induced genetic and oxidative damages in rats. Selected animals were assigned to four groups (n = 6), namely, group A: control (only distilled water is injected); group B: AlP (4 mg kg(-1) injected intraperitoneally (i.p.)); group C: LNE (200 mg kg(-1) injected i.p.), and group D: AlP plus LNE, respectively. The experimental period lasted for 14 successive days. Chromosomal aberrations (CAs) and micronucleus (MN) assay were used for monitoring genotoxic damage. In addition, biochemical parameters such as total antioxidant capacity (TAC) and total oxidative status (TOS) were examined in serum samples to determine oxidative damage. Our results indicated that AlP caused increase in CA and MN assay rates and alterations in TAC and TOS levels when compared with control group. On the contrary, LNE did not change the rates of both the analyzed cytogenetic end points and led to increase in TAC level. Moreover, we observed that LNE suppressed the genetic damage by AlP to bone marrow cells in vivo. Interestingly AlP-induced oxidative stress was also strongly reduced by LNE. The results of the present study indicated that the protective effect of LNE might be ascribable to its antioxidant and free radical scavenging properties. PMID- 22294442 TI - Ginkgo biloba and Angelica archangelica bring back an impartial hepatic apoptotic to anti-apoptotic protein ratio after exposure to technetium 99mTc. AB - PURPOSE: The aim of this study was to study the effect of ionizing radiation on apoptosis-related protein concentrations as well as the radio-protective role of Ginkgo biloba and Angelica archangelica. The experiments were performed on 68 adult Wistar rats weighing 175 g (+/-10 g). Animals were subdivided into control group in which the animals received neither the protector nor the isotopes. The second group represents the animals that received 1 mCi of (99m)Tc only. The third group represents the animals that received A. archangelica for 7 days. The fourth group represents the animals that received G. biloba for 7 days. The fifth group represents the animals that received 1 mCi of (99m)Tc once after receiving A. archangelica for 7 days. The sixth group represents the animals that received mCi of (99m)Tc once after receiving G. biloba for 7 days. Radiation was administered as intravenous injection by 1 mCi of (99m)Tc with the legend methoxyisobutylisonitrile for 24 h. The concentration of p53, Bcl2 and malondialdehyde in liver as well as histopathological examination of liver cells were carried out. Results showed that apoptotic to anti-apoptotic protein ratio significantly (p < 0.05) returned to its normal ratio when radioisotopic injection was administered after the protection period for a week by both A. archangelica and G. biloba in a dose based on the animal body weight. Electron microscope photographing supported this finding. CONCLUSION: It was concluded that both antioxidants can be used as radio-protective agents in cases of ionizing radiation exposure. PMID- 22294443 TI - Detection of polycyclic aromatic hydrocarbons in different types of processed foods. AB - Polycyclic aromatic hydrocarbons (PCAHs), particularly those with a high molecular weight, have been classified as probable carcinogens to humans. The aim of the present study is to determine the levels of PCAHs in samples of meat, fish, chicken, fried potato, and toasted bread, which will be thermally processed using conventional and microwave ovens. Different samples will be collected and analyzed for five PCAHs including pyrene, benzo(a)anthracene, benzo(e)pyrene, benzoflouroanthene, and benzo(a)pyrene. The analytical method involves saponification with methanolic potassium hydroxide, extraction with cyclohexane, and determination by high-performance liquid chromatography. The obtained results showed that there is a variation in the detected PCAHs in different foodstuffs. Fried potato processed by conventional oven or microwave oven showed none of the selected studied PCAHs. It was found that, chicken showed higher content levels of total PCAHs than the meat and fish. Data are the highest mean concentrations of fluoranthene and benzo(a)pyrene but within low limit. The obtained results were compared with international permissible levels to avoid pollution, which may cause hazardous effects on individual and society. PMID- 22294444 TI - Characterization of multiple first exons in murine prolactin receptor gene and the effect of prolactin on their expression in the choroid plexus. AB - Prolactin (Prl) receptor (Prlr) gene is expressed in various brain regions, with the highest level present in the choroid plexus, a site for receptor-mediated PRL transport from the blood to cerebrospinal fluid. We investigated the regulatory mechanism of Prlr gene expression by PRL in the murine choroid plexus. We first examined the organization of the alternative first exons in murine Prlr gene. In addition to the three known first exons, mE1(1), mE1(2), and mE1(3), two first exons, mE1(4) and mE1(5), were newly identified by cDNA cloning. Each first exon variant of Prlr mRNA exhibited tissue-specific or generic expression. In the choroid plexus of mice, the expression levels of mE1(3)-, mE1(4)-, and mE1(5) Prlr mRNAs were increased in the lactating mice compared with those in the diestrus mice. Furthermore, the expression level of mE1(4)-Prlr mRNA was decreased in the PRL-deficient (Prl(-/-)) mice compared with the PRL-normal (Prl(+/+) and Prl(+/-)) mice. In the ovariectomized Prl(-/-) mice, the expression level of mE1(4)-Prlr mRNA was significantly increased by PRL administration but not by 17beta-estradiol administration. The expression levels of the two last exon variants of Prlr mRNAs, encoding the long and short cytoplasmic regions of PRLR, were also increased in the lactating mice and decreased in the Prl(-/-) mice. These findings suggest that PRL stimulates the Prlr gene expression through the transcriptional activation of mE1(4) first exon, leading to increases in the long- and short-form variants of Prlr mRNA in the murine choroid plexus. PMID- 22294445 TI - Sequence variation analysis of the E2 gene of human papilloma virus type 16 in cervical lesions from women in Greece. AB - The E2 gene of human papilloma virus is expressed at the early stage of the viral life cycle, encoding the E2 transcription factor, and regulates the expression of E6 and E7 oncogenes. Disruption of E2 gene due to viral integration inhibits the transcriptional suppression of the HPV oncogenes, inducing cell proliferation. In the present study, a total of 22 HPV16-positive cytological specimens derived from high- and low-grade cervical intraepithelial lesions were investigated in order to identify sequence variations in the HPV16 E2 ORF. The E2 gene was amplified by PCR using external and internal overlapping sets of primers. Amplicons were cloned and sequenced. Disruption sites were detected in cervical samples diagnosed as high-grade cervical intraepithelial lesions. Moreover, sequence variations were identified in the E2 ORF and specific variations were associated with non-European variants such as African type I, African type II and Asian American. A total of three new sequence variations were identified at positions 2791, 2823 (transactivation domain) and 3361 (hinge region). Distinct phylogenetic branches were formed according to E2 analysis that characterized the different HPV16 variants. It was ascertained that non-European variants are circulating in the Greek population. PMID- 22294446 TI - Superiority of the buffy coat over serum or plasma for the detection of Alkhumra virus RNA using real time RT-PCR. AB - RT-PCR to detect Alkhumra virus (ALKV) RNA in plasma or serum has been the standard practice to confirm this infection in the first seven days of illness. In this study, RT-PCR detection of viral RNA from the plasma, serum, and buffy coat (BC) was compared to virus isolation. Plasma, serum, and BC were obtained from seven patients with clinically suspected ALKV infection in Najran, Saudi Arabia. Baby hamster kidney (BHK-21) and rhesus monkey kidney (LLC-MK2) cell culture monolayers were used for virus isolation. Real-time RT-PCR was used to confirm ALKV infection and to detect viral RNA directly from plasma, serum, and BC. ALKV was isolated from five of the seven patients. The virus was isolated from all three specimen types (plasma, serum, and BC) of the five confirmed patients. ALKV RNA was detected directly by RT-PCR in BC in all five (100%) culture-positive patients and in plasma or serum in only four (80%) of the five patients. Three of the five patients for whom ALKV RNA was detected in BC also had detectable viral RNA in plasma and serum. In the remaining two patients with detectable ALKV RNA in the BC, the plasma was positive but the serum was negative in one patient, whereas the serum was positive and the plasma was negative in the other patient. The use of real-time RT-PCR to detect ALKV RNA in the BC was superior to using plasma and serum and equivalent to virus isolation. PMID- 22294447 TI - A DNA vaccine expressing PB1 protein of influenza A virus protects mice against virus infection. AB - Although influenza DNA vaccine research has focused mainly on viral hemagglutinin and has led to promising results, other virion proteins have also shown some protective potential. In this work, we explored the potential of a DNA vaccine based on the PB1 protein to protect BALB/c mice against lethal influenza A virus infection. The DNA vaccine consisted of pTriEx4 plasmid expressing PB1. As a positive control, a pTriEx4 plasmid expressing influenza A virus HA was used. Two weeks after three subcutaneous doses of DNA vaccine, the mice were challenged intranasally with 1 LD50 of A/Puerto Rico/8/34 (H1N1) virus, and PB1- and HA specific antibodies, survival rate, body weight change, viral mRNA load, infectious virus titer in the lungs, cytokines IL-2, IL-4 and IL-10, and granzyme B were measured. The results showed that (i) the PB1-expressing DNA vaccine provided a fair protective immunity in the mouse model and (ii) viral structural proteins such as PB1 represent promising antigens for DNA vaccination against influenza A. PMID- 22294448 TI - A unified impulse response model for DCE-MRI. AB - We describe the gamma capillary transit time model, a generalized impulse response model for DCE-MRI that mathematically unifies the Tofts-Kety, extended Tofts-Kety, adiabatic tissue homogeneity, and two-compartment exchange models. By including a parameter (alpha-1) representing the width of the distribution of capillary transit times within a tissue voxel, the GCTT model discriminates tissues having relatively monodisperse transit time distributions from those having a large degree of heterogeneity. All five models were compared using in vivo data acquired in three brain tumors (one glioblastoma multiforme, one pleomorphic xanthoastrocytoma, and one anaplastic meningioma) and Monte Carlo simulations. Our principal findings are : (1) The four most commonly used models for dynamic contrast-enhanced magnetic resonance imaging can be unified within a single formalism. (2) Application of the GCTT model to in vivo data incurs only modest penalties in parameter uncertainty and computational cost. (3) Measured nonparametric impulse response functions in human brain tumors are well described by the GCTT model. (4) Estimation of alpha-1 is feasible but achieving statistical significance requires higher SNR than is typically obtained in single voxel dynamic contrast-enhanced magnetic resonance imaging data. These results suggest that the GCTT model may be useful for extraction of information about tumor physiology beyond what is obtained using current modeling methodologies. PMID- 22294449 TI - Unusual endoscopic appearance of Crohn's disease: another face of a multifaceted disease. PMID- 22294450 TI - Characterization of active miniature inverted-repeat transposable elements in the peanut genome. AB - Miniature inverted-repeat transposable elements (MITEs), some of which are known as active nonautonomous DNA transposons, are found in the genomes of plants and animals. In peanut (Arachis hypogaea), Ah-MITE1 has been identified in a gene for fatty-acid desaturase, and possessed excision activity. However, the AhMITE1 distribution and frequency of excision have not been determined for the peanut genome. In order to characterize AhMITE1s, their genomic diversity and transposition ability was investigated. Southern blot analysis indicated high AhMITE1 copy number in the genomes of A. hypogaea, A. magna and A. monticola, but not in A. duranensis. A total of 504 AhMITE1s were identified from the MITE enriched genomic libraries of A. hypogaea. The representative AhMITE1s exhibited a mean length of 205.5 bp and a GC content of 30.1%, with AT-rich, 9 bp target site duplications and 25 bp terminal inverted repeats. PCR analyses were performed using primer pairs designed against both flanking sequences of each AhMITE1. These analyses detected polymorphisms at 169 out of 411 insertional loci in the four peanut lines. In subsequent analyses of 60 gamma-irradiated mutant lines, four Ah-MITE1 excisions showed footprint mutations at the 109 loci tested. This study characterizes AhMITE1s in peanut and discusses their use as DNA markers and mutagens for the genetics, genomics and breeding of peanut and its relatives. PMID- 22294451 TI - Clinical images: transverse acroosteolysis. PMID- 22294452 TI - Jacob B. Winslow (1669-1760). AB - Jacob Winslow was a Dutch born, French naturalized anatomist and physician whose contributions to medicine are abundant. His importance to medicine is undisputed. His personal life included a religious crisis that resulted in his estrangement from his family, but afforded him patrons in Paris to continue his work. Following this conversion, he changed his name to that of his catechist and was rechristened Jacques Benigne Wilson. His respect as an expert was well deserved, and he held several prominent positions during his career in Paris. His main work, Exposition anatomique de la structure du corps humain, was published in 1732 and is considered the first purely anatomical treatise. This review highlights his contributions to anatomy and medicine through the course of his career. PMID- 22294453 TI - Comparison of the spores of Paenibacillus polymyxa prepared at different temperatures. AB - Paenibacillus polymyxa SQR-21, which is antagonistic against Fusarium oxysporum, is used as a biocontrol agent and, when mixed with organic substances for solid fermentation, produces a bioorganic fertilizer. The spores of P. polymyxa prepared at different temperatures were characterized with respect to the dipicolinic acid content, heat resistance, fatty acid composition and germination. Spores prepared at 37 degrees C showed higher heat resistance than those prepared at 25 and 30 degrees C. However, the germination rate was negatively correlated with the sporulation temperature. The maximum germination rate of the spores prepared at 25 degrees C was 1.3-times higher than the spores prepared at 30 degrees C. The sporulation temperature thus affects the resistance and germination properties of P. polymyxa spores. These results are useful for the production of improved bio-organic fertilizer. PMID- 22294454 TI - Anxiolytic-like effect of alpha-asarone in mice. AB - The effects of alpha-asarone in four assays predictive of anxiolytic activity in male mice were studied, with diazepam as a positive anxiolytic control. The use of the elevated plus-maze test revealed that diazepam (2 mg/kg) or alpha-asarone (3.5 mg/kg) increased the percentage of entries into open arms and of the time spent on open arms. In the light/dark transition test, as with 2 mg/kg diazepam, 7 mg/kg alpha-asarone increased the time spent in the light area and the number of transitions between the two compartments. In the novel food consumption test, alpha-asarone (3.5, 7 and 14 mg/kg) caused significant increases in food intake during 5 min as well as diazepam (0.5 mg/kg). In the marble burying test, alpha asarone also produced a significant inhibition of marble burying at doses of 14 and 28 mg/kg, as did diazepam (5 mg/kg). Thus, these findings indicated that alpha-asarone exhibited an anxiolytic-like effect. Further studies will be required to assess the generality of the present findings to other species and behavioral paradigms. PMID- 22294455 TI - Monitoring peripheral blood CD4(+) intracellular adenosine triphosphate concentration in patients with psoriasis treated with fumaric acid esters. PMID- 22294456 TI - Harnessing human plasmacytoid dendritic cells as professional APCs. AB - The plasmacytoid dendritic cell (pDC) constitutes a unique DC subset that links the innate and adaptive arm of the immune system. Whereas the unique capability of pDCs to produce large amounts of type I IFNs in response to pathogen recognition is generally accepted,their antigen-presenting function is often neglected since most studies on antigen presentation are aimed at other DC subsets. Recently, pDCs were demonstrated capable to present antigen leading to protective tumor immunity. In this review, we discuss how pDCs could be exploited in the fight against cancer by analyzing their capacity to capture,process and (cross-) present antigen. PMID- 22294457 TI - Internal tumor burden in neurofibromatosis Type I patients with large NF1 deletions. AB - Neurofibromatosis Type 1 (NF1) is a frequent tumor suppressor gene disorder characterized by multiple benign tumors and high risk of malignancy. Internal tumor burden is a major disease-associated manifestation and can be most adequately assessed by magnetic resonance imaging of the whole body. Approximately 5% of NF1 patients have constitutional large NF1-deletions that are generally associated with more severe clinical manifestations. Here, we investigated whether these deletion patients also have more and/or larger internal tumors by assessing internal tumors and their total volume (exclusive of cutaneous and subcutaneous) in 38 NF1 deletion patients (including eight mosaic cases) and 114 age- and gender-matched NF1 patients without deletions. The incidence of internal tumors was significantly lower in mosaic deletion patients (1/8 = 13%) but did not differ between the 30 nonmosaic deletion patients and the 90 age- and gender-matched NF1 patients without large deletions used as controls. Neither the number nor the total volume of tumors per patient differed significantly between the latter two groups. However, extremely high tumor burden (>3,000 ml) was significantly more frequent among nonmosaic NF1 deletion patients than among NF1 patients without large deletions (13% vs. 1%, P = 0.014). Thus, as a group, patients with NF1 deletions do not exhibit a significantly higher internal tumor burden than NF1 patients without such deletions. However, deletion patients can frequently have extremely large internal tumors and thus demand special attention. PMID- 22294458 TI - Influence of lipid composition and drug load on the In Vitro performance of self nanoemulsifying drug delivery systems. AB - The influence of lipid composition and drug load on the in vitro performance of lipid-based drug delivery systems was investigated during dispersion and in vitro lipolysis of two self-nanoemulsifying drug delivery systems (SNEDDS). SNEDDS preconcentrates consisted of the same mass ratios of lipid, surfactant, and cosolvent but varied in the chain length of the lipid component. Utilization of the surfactant Cremophor EL resulted in pronounced changes in the droplet size of dispersed SNEDDS containing increasing drug loads of the poorly water-soluble compound simvastatin (SIM). In contrast, the droplet size of dispersed medium chain (MC)-SNEDDS based on the surfactant Cremophor RH40 was not affected by increasing drug loads of SIM, whereas the droplet size of the corresponding long chain (LC)-SNEDDS increased. During 60 min in vitro lipolysis, MC-SNEDDS maintained approximately 95% of SIM in solution, independent of the drug load. At the start of lipolysis of LC-SNEDDS, up to 34% of the drug precipitated. However, the initial precipitate dissolved in the lipolysis medium 30 min after start of in vitro lipolysis. The study suggests that drug load and lipid composition should be considered for the design of SNEDDS. (c) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:1721-1731, 2012. PMID- 22294459 TI - A phase 1 trial of E7974 administered on day 1 of a 21-day cycle in patients with advanced solid tumors. AB - BACKGROUND: E7974, a synthetic analog of hemiasterlin, interacts with the tubulin molecule and overcomes resistance to other antitubulin drugs (taxanes and vinca alkaloids). METHODS: In a phase 1 study, E7974 was given intravenously over a 2- to 5-minute infusion on day 1 of every 21-day cycle. Adult patients with advanced refractory solid tumors who had adequate organ function and Eastern Cooperative Oncology Group performance status 0 to 2 were eligible for this study. A modified Fibonacci schema was used. The maximal tolerated dose (MTD) was the dose where <2 of 6 patients developed a dose-limiting toxicity (DLT). RESULTS: Twenty-eight patients (19 men and 9 women; median age, 64 years) treated at different cohort dose levels (0.18 mg/m(2) , 0.27 mg/m(2) , 0.36 mg/m(2) , 0.45 mg/m(2) , and 0.56 mg/m(2) ) received a total of 66 courses of E7974. The MTD was established at 0.45 mg/m(2) , where 1 of 6 patients experienced DLT (grade 4 febrile neutropenia). Of the 17 refractory colon cancer patients with a median of 3 prior treatments, stable disease was seen in 7 patients (41%). There were no tumor responses. Median progression-free survival was 1.2 months, and median overall survival was 6.7 months. In pharmacokinetic analysis, E7974 was characterized by a fast and moderately large distribution (37.95-147.93 L), slow clearance (2.23 7.15 L/h), and moderate to slow elimination (time to half-life, 10.4-30.5 hours). CONCLUSIONS: This study shows that E7974 once every 21-day cycle shows antitumor activity in patients with refractory solid tumors. The recommended phase 2 dose is 0.45 mg/m(2). PMID- 22294460 TI - Childhood aggression, callous-unemotional traits and oxytocin genes. AB - Given the known behavior effects of oxytocin,and in particular its putative effect on trust, affiliation and anxiety, we hypothesized that oxytocin may be involved in the development and expression of callous-unemotional traits in children with aggressive antisocial behavior. We recruited 162 children between the ages of 6 and 16. The majority of subjects were Caucasian (84.0%) compared to African-Canadian (4.9%) and others (11.1%). The oxytocin and oxytocin receptor gene polymorphisms were genotyped and analyzed for possible association with child aggression in a case-control study design as well as with callous unemotional traits in a within cases analysis. We did not have significant findings with our tested OXTR markers in the case-control analysis. We found the OXTR_rs237885 AA genotype carriers to score higher than AC or CC genotype carriers on the callous-unemotional traits. This result remained significant following correction for multiple testing. No other markers were found to be significant. However, the haplotype consisting of the OXTR_rs237885 A allele and OXTR_rs2268493 A allele was associated with significantly higher callous unemotionals cores than other haplotypes. This is the first known study to show a significant association between callous unemotional traits in children and adolescents with extreme, persistent pervasive aggression and a polymorphism on the oxytocin receptor. Given the small sample size and the possibility of false positive effects, the need to replicate and verify these findings is required. PMID- 22294461 TI - Cellular response of healing tissue to DegraPol tube implantation in rabbit Achilles tendon rupture repair: an in vivo histomorphometric study. AB - In tendon rupture repair, improvements such as higher primary repair strength, anti-adhesion and accelerated healing are needed. We developed a potential carrier system of an electrospun DegraPol tube, which was tightly implanted around a transected and conventionally sutured rabbit Achilles tendon. Histomorphometric analysis of the tendon tissue 12 weeks postoperation showed that the tenocyte density, tenocyte morphology and number of inflammation zones were statistically equivalent, whether or not DegraPol tube was implanted; only the collagen fibres were slightly less parallelly orientated in the tube-treated case. Comparison of rabbits that were operated on both hind legs with ones that were operated on only one hind leg showed that there were significantly more inflammation zones in the two-leg cases compared to the one-leg cases, while the implantation of a DegraPol tube had no such adverse effects. These findings are a prerequisite for using DegraPol tube as a carrier system for growth factors, cytokines or stem cells in order to accelerate the healing process of tendon tissue. PMID- 22294462 TI - Pediatric T-cell acute lymphoblastic leukemia with transient pure red cell aplasia. PMID- 22294464 TI - Copper deficiency has minimal impact on ferroportin expression or function. AB - Interactions between copper and iron homeostasis have been known since the nineteenth century when anemia in humans was first described due to copper limitation. However, the mechanism remains unknown. Intestinal and liver iron concentrations are usually higher following copper deficiency (CuD). This may be due to impaired function of the multicopper oxidases hephaestin or ceruloplasmin (Cp), respectively. However, iron retention could be due to altered ferroportin (Fpn), the essential iron efflux transporter in enterocytes and macrophages. Fpn mRNA is controlled partially by intracellular iron and IRE dependence. CuD should augment Fpn based on iron level. Some argue that Fpn stability is controlled partially by membrane ferroxidase (GPI-Cp). CuD should result in lower Fpn since GPI-Cp expression and function is reduced. Fpn turnover is controlled by hepcidin. CuD results in variable Hamp (hepcidin) expression. Fpn mRNA and protein level were evaluated following dietary CuD in rats and mice. To correlate with Fpn expression, measurements of tissue iron were conducted in several rodent models. Following CuD there was little change in Fpn mRNA. Previous work indicated that under certain circumstances Fpn protein was augmented in liver and spleen following CuD. Fpn levels in CuD did not correlate with either total iron or non-heme iron (NHI), as iron levels in CuD liver were higher and in spleen lower than copper adequate controls. Fpn steady state levels appear to be regulated by a complex set of factors. Changes in Fpn do not explain the anemia of CuD. PMID- 22294463 TI - Known and potential roles of transferrin in iron biology. AB - Transferrin is an abundant serum metal-binding protein best known for its role in iron delivery. The human disease congenital atransferrinemia and animal models of this disease highlight the essential role of transferrin in erythropoiesis and iron metabolism. Patients and mice deficient in transferrin exhibit anemia and a paradoxical iron overload attributed to deficiency in hepcidin, a peptide hormone synthesized largely by the liver that inhibits dietary iron absorption and macrophage iron efflux. Studies of inherited human disease and model organisms indicate that transferrin is an essential regulator of hepcidin expression. In this paper, we review current literature on transferrin deficiency and present our recent findings, including potential overlaps between transferrin, iron and manganese in the regulation of hepcidin expression. PMID- 22294465 TI - Serum anti-glycan antibody biomarkers for inflammatory bowel disease diagnosis and progression: a systematic review and meta-analysis. AB - BACKGROUND: Anti-glycan antibody serologic markers may serve as a useful adjunct in the diagnosis/prognosis of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). This meta-analysis/systemic review aimed to evaluate the diagnostic value, as well as the association of anti-glycan biomarkers with IBD susceptible gene variants, disease complications, and the need for surgery in IBD. METHODS: The diagnostic odds ratio (DOR), 95% confidence interval (CI), and sensitivity/specificity were used to compare the diagnostic value of individual and combinations of anti-glycan markers and their association with disease course (complication and/or need for surgery). RESULTS: Fourteen studies were included in the systemic review and nine in the meta-analysis. Individually, anti-Saccharomyces cervisiae antibodies (ASCA) had the highest DOR for differentiating IBD from healthy (DOR 21.1; 1.8-247.3; two studies), and CD from UC (DOR 10.2; CI 7.7-13.7; seven studies). For combination of >=2 markers, the DOR was 2.8 (CI 2.2-3.6; two studies) for CD-related surgery, higher than any individual marker, while the DOR for differentiating CD from UC was 10.2 (CI 5.6 18.5; three studies) and for complication was 2.8 (CI 2.2-3.7; two studies), similar to individual markers. CONCLUSIONS: ASCA had the highest diagnostic value among individual anti-glycan markers. While anti-chitobioside carbohydrate antibody (ACCA) had the highest association with complications, ASCA and ACCA associated equally with the need for surgery. Although in most individual studies the combination of >=2 markers had a better diagnostic value as well as higher association with complications and need for surgery, we found the combination performing slightly better than any individual marker in our meta-analysis. PMID- 22294466 TI - Foot anomalies and proximal symphalangism. AB - We report the case of a 2-week-old girl born at term (by vaginal delivery and without antenatal or perinatal events) who was referred as having "bilateral talipes and bilateral proximal symphalangism of little and ring fingers." The "talipes" was atypical with marked equinus and varus, but no cavus or adductus of the midfoot. Her mother had both symphalangism (absence of proximal interphalangeal joints) of middle, ring, and little fingers bilaterally and fixed pes planus with a rigid fixed hindfoot-and these deformities had also been present from birth. The maternal grandmother was similarly affected. However, the neonatal subject has an unaffected older sibling; maternal siblings are also unaffected. The three affected people did not have other obvious musculoskeletal abnormalities. Because of the coalitions, the child's atypical talipes was managed by a modified Kite's procedure. Symphalangism-coalition syndromes may be associated with conductive deafness because of fusion of the auditory ossicles. PMID- 22294467 TI - Improved dynamic response assessment for intra-articular injected iron oxide nanoparticles. AB - The emerging importance of nanoparticle technology, including iron oxide nanoparticles for monitoring development, progression, and treatment of inflammatory diseases such as arthritis, drives development of imaging techniques. Studies require an imaging protocol that is sensitive and quantifiable for the detection of iron oxide over a wide range of concentrations. Conventional signal loss measurements of iron oxide nanoparticle containing tissues saturate at medium concentrations and show a nonlinear/nonproportional intensity to concentration profile due to the competing effects of T1 and T2 relaxation. A concentration calibration phantom and an in vivo study of intra articular injection in a rat knee of known concentrations of iron oxide were assessed using the difference-ultrashort echo time sequence giving a positive, quantifiable, unambiguous iron signal and monotonic, increasing concentration response over a wide concentration range in the phantom with limited susceptibility artifacts and high contrast in vivo to all other tissues. This improved dynamic response to concentration opens possibilities for quantification due to its linear nature at physiologically relevant concentrations. PMID- 22294468 TI - Inhibition of NF- kappaB activity by minor polar components of extra-virgin olive oil at gastric level. AB - The present work evaluates the effect of olive oil phenols on NF-kappaB activity in human gastric adenocarcinoma cells. The total phenol content was measured by the Folin Ciocalteu method, whereas the composition was assessed by LC-MS/MS analysis. Secoiridoids represented 71% and 83% of the Italian and Spanish extracts, respectively, phenol alcohols were in the range 9-13%. Ligustroside aglycone was the most abundant (37% and 46%, respectively, in the Italian and Spanish sample), and the concentration of flavonoids AP and LU was below 1%. Phenol extracts were assayed at 0.25-7.5 ug/mL, whereas single compounds were at 0.5-25 uM. Both the extracts inhibited the NF-kappaB driven transcription in a concentration-dependent manner: IC(50) for the Italian and the Spanish extract were 0.86 and 1.28 ug/mL, respectively. The IC(50) for individual compounds ranged from 4.5 to 13 uM. All the compounds under study inhibited nuclear translocation as well. The data suggest that consumption of extra-virgin olive oil may be beneficial for preventing the onset of gastric inflammation leading to more serious diseases. PMID- 22294469 TI - Inflammatory regulation of glucocorticoid metabolism in mesenchymal stromal cells. AB - OBJECTIVE: Tissue glucocorticoid (GC) levels are regulated by the GC-activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). This enzyme is expressed in cells and tissues arising from mesenchymal stromal cells. Proinflammatory cytokines dramatically increase expression of 11beta-HSD1 in stromal cells, an effect that has been implicated in inflammatory arthritis, osteoporosis, obesity, and myopathy. Additionally, GCs act synergistically with proinflammatory cytokines to further increase enzyme expression. The present study was undertaken to investigate the mechanisms underlying this regulation. METHODS: Gene reporter analysis, rapid amplification of complementary DNA ends (RACE), chemical inhibition experiments, and genetic disruption of intracellular signaling pathways in mouse embryonic fibroblasts (MEFs) were used to define the molecular mechanisms underlying the regulation of 11beta-HSD1 expression. RESULTS: Gene reporter, RACE, and chemical inhibitor studies demonstrated that the increase in 11beta-HSD1 expression with tumor necrosis factor alpha (TNFalpha)/interleukin-1beta (IL-1beta) occurred via the proximal HSD11B1 gene promoter and depended on NF-kappaB signaling. These findings were confirmed using MEFs with targeted disruption of NF-kappaB signaling, in which RelA (p65) deletion prevented TNFalpha/IL-1beta induction of 11beta-HSD1. GC treatment did not prevent TNFalpha-induced NF-kappaB nuclear translocation. The synergistic enhancement of TNFalpha-induced 11beta-HSD1 expression with GCs was reproduced by specific inhibitors of p38 MAPK. Inhibitor and gene deletion studies indicated that the effects of GCs on p38 MAPK activity occurred primarily through induction of dual-specificity phosphatase 1 expression. CONCLUSION: The mechanism by which stromal cell expression of 11beta-HSD1 is regulated is novel and distinct from that in other tissues. These findings open new opportunities for development of therapeutic interventions aimed at inhibiting or stimulating local GC levels in cells of mesenchymal stromal lineage during inflammation. PMID- 22294470 TI - Midostaurin does not prolong cardiac repolarization defined in a thorough electrocardiogram trial in healthy volunteers. AB - PURPOSE: Midostaurin (PKC412) is a multitargeted tyrosine kinase inhibitor of FMS like tyrosine kinase 3 receptor (FLT3), c-KIT, and other receptors. Midostaurin is active in patients with acute myeloid leukemia and systemic mastocytosis. Although no substantive risk for cardiac abnormalities has been observed with midostaurin in clinical studies thus far, some TKIs have been shown to affect cardiac repolarization. Here we evaluated midostaurin's effect on cardiac repolarization. METHODS: This phase I study evaluated the effect of midostaurin (75 mg twice daily for 2 days; 75 mg once on day 3) on the heart rate-corrected QT (QTc) interval in a parallel design with active (moxifloxacin) and placebo control arms in healthy volunteers. RESULTS: The maximum mean QTc change from baseline corrected using Fridericia's correction (QTcF) for midostaurin compared with placebo was 0.7 ms at 24 h post dose on day 3. The highest upper bound of the 1-sided 95% CI was 4.7 ms, which excluded 10 ms, demonstrating a lack of QTcF prolongation effect. Assay sensitivity was demonstrated by modeling the moxifloxacin plasma concentration versus QTcF change from baseline, which showed a clear positive increase in QTcF with increasing moxifloxacin plasma concentrations, as expected based on previous studies. In the 4-day evaluation period, a minority of participants (34.6%) experienced an adverse event; 97.0% were grade 1. No grade 3 or 4 adverse events were reported. CONCLUSION: Midostaurin demonstrated a good safety profile in healthy volunteers, with no prolonged cardiac repolarization or other changes on the electrocardiogram. PMID- 22294473 TI - C reactive protein: impact on peripheral tissue oxygenation and perfusion in neonates. AB - OBJECTIVE: C reactive protein (CRP) is a sensitive marker of acute inflammation of infectious and non-infectious origin. Aim was to use near-infrared spectroscopy (NIRS) to analyse peripheral oxygenation and perfusion in term and preterm neonates with elevated CRP levels, at a time when routine haemodynamic variables are still normal. DESIGN: Prospective observational study. SETTINGS: Peripheral-muscle NIRS was performed in the first week of life. Tissue oxygenation index (TOI), mixed venous oxygenation (SvO(2)), fractional oxygen extraction (FOE), haemoglobin flow (Hbflow), oxygen delivery (DO(2)) and oxygen consumption (VO(2)) were assessed. Blood samples were taken within 3 h of the NIRS measurements. PATIENTS: Cardiocirculatory stable term and preterm neonates with infection-related and infection-unrelated CRP elevations >10 mg/l were compared with neonates without CRP elevation. The two groups were matched for gestational and postnatal age. RESULTS: 33 neonates with CRP elevation (gestational age 37.7+/-2.9 weeks) were compared with 33 controls (gestational age 37.3+/-2.9 weeks). In neonates with CRP elevation, TOI (68.9+/-6.6%), SvO(2) (66.9+/-7.3%) DO(2) (39.2+/-16.1 umol/100ml/min) and VO(2) (10.9+/-3.4 umol/100ml/min) were significantly lower compared with controls (TOI 72.9+/-3.8%, SvO(2) 70.2+/-4.7%, DO(2) 48.8+/-18.4 umol/100ml/min, VO(2) 12.3+/-3.8 umol/100ml/min). There was no significant difference in any other NIRS or routine haemodynamic parameter between the two groups. CONCLUSION: Inflammatory processes with CRP elevation cause impaired peripheral oxygenation and perfusion in neonates even when routine haemodynamic variables are still normal. NIRS might offer a new non-invasive tool for the early recognition and diagnosis of infectious and non-infectious inflammatory processes. PMID- 22294475 TI - Risk factors for early sudden deaths and severe apparent life-threatening events. AB - OBJECTIVE: To identify potential risk factors for unexpected sudden infant deaths (SID) and severe apparent life-threatening events (S-ALTE) within 24 h of birth. DESIGN: Case-control study embedded in an epidemiological survey over a 2-year period. PATIENTS AND METHODS: Throughout 2009, every paediatric department in Germany was asked to report cases of unexplained SID or S-ALTE in term infants with a 10-min Apgar score >=8 to the Surveillance Unit for Rare Pediatric Conditions. Throughout 2010, the inclusion criteria were extended to infants >=35 week gestational age and those where an explanation for the deterioration had been found. For each unexplained case, hospitals were asked to fill in a questionnaire for 3 (near-)term controls with good postnatal adaptation at the age (in minutes) when the event had occurred in the case under study. RESULTS: Of the 85 cases reported, 34 fulfilled the entry criteria; of these, two were near term newborns and, in three cases, a cause had been identified for the event. For the 31 cases with unknown cause for the event (13 males; mean (SD) gestational age 38.9 (1.7) week), the authors gathered 93 controls (51 male infants; 38.9 (1.4) week). As significant risk factors for S-ALTE and SID, the authors could identify primipara (OR 6.22; 95% CI 2.11 to 18.32) and potentially asphyxiating position (OR 6.45; 95% CI 1.22 to 34.10). CONCLUSIONS: Close observation of newborns seems necessary, particularly in primipara; a potentially asphyxiating position should be avoided. PMID- 22294476 TI - Arbuscular mycorrhizal symbiosis increases relative apoplastic water flow in roots of the host plant under both well-watered and drought stress conditions. AB - BACKGROUND AND AIMS: The movement of water through mycorrhizal fungal tissues and between the fungus and roots is little understood. It has been demonstrated that arbuscular mycorrhizal (AM) symbiosis regulates root hydraulic properties, including root hydraulic conductivity. However, it is not clear whether this effect is due to a regulation of root aquaporins (cell-to-cell pathway) or to enhanced apoplastic water flow. Here we measured the relative contributions of the apoplastic versus the cell-to-cell pathway for water movement in roots of AM and non-AM plants. METHODS: We used a combination of two experiments using the apoplastic tracer dye light green SF yellowish and sodium azide as an inhibitor of aquaporin activity. Plant water and physiological status, root hydraulic conductivity and apoplastic water flow were measured. KEY RESULTS: Roots of AM plants enhanced significantly relative apoplastic water flow as compared with non AM plants and this increase was evident under both well-watered and drought stress conditions. The presence of the AM fungus in the roots of the host plants was able to modulate the switching between apoplastic and cell-to-cell water transport pathways. CONCLUSIONS: The ability of AM plants to switch between water transport pathways could allow a higher flexibility in the response of these plants to water shortage according to the demand from the shoot. PMID- 22294477 TI - Morphologies and elemental compositions of calcium crystals in phyllodes and branchlets of Acacia robeorum (Leguminosae: Mimosoideae). AB - BACKGROUND AND AIMS: Formation of calcium oxalate crystals is common in the plant kingdom, but biogenic formation of calcium sulfate crystals in plants is rare. We investigated the morphologies and elemental compositions of crystals found in phyllodes and branchlets of Acacia robeorum, a desert shrub of north-western Australia. METHODS: Morphologies of crystals in phyllodes and branchlets of A. robeorum were studied using scanning electron microscopy (SEM), and elemental compositions of the crystals were identified by energy-dispersive X-ray spectroscopy. Distributional patterns of the crystals were studied using optical microscopy together with SEM. KEY RESULTS: According to the elemental compositions, the crystals were classified into three groups: (1) calcium oxalate; (2) calcium sulfate, which is a possible mixture of calcium sulfate and calcium oxalate with calcium sulfate being the major component; and (3) calcium sulfate . magnesium oxalate, presumably mixtures of calcium sulfate, calcium oxalate, magnesium oxalate and silica. The crystals were of various morphologies, including prisms, raphides, styloids, druses, crystal sand, spheres and clusters. Both calcium oxalate and calcium sulfate crystals were observed in almost all tissues, including mesophyll, parenchyma, sclerenchyma (fibre cells), pith, pith ray and cortex; calcium sulfate . magnesium oxalate crystals were only found in mesophyll and parenchyma cells in phyllodes. CONCLUSIONS: The formation of most crystals was biologically induced, as confirmed by studying the crystals formed in the phyllodes from seedlings grown in a glasshouse. The crystals may have functions in removing excess calcium, magnesium and sulfur, protecting the plants against herbivory, and detoxifying aluminium and heavy metals. PMID- 22294478 TI - Tissue remodeling gene expression in a murine model of chronic rhinosinusitis. AB - OBJECTIVE/HYPOTHESIS: The matrix metalloproteinase (MMP), fibroblast growth factor (FGF), and bone morphogenetic protein (BMP) families regulate tissue remodeling in many normal and pathophysiologic processes. We hypothesize that induction of chronic sinonasal inflammation will be associated with changes in regulation of these tissue remodeling cytokines. METHODS: Balb/c mice aged 8 to 12 weeks were sensitized and treated with intranasal Aspergillus fumigatis (AF) three times per week for 1 week, 3 weeks, 2 months, and 3 months (n = 8 each time point). Sinonasal tissues were evaluated for changes in MMP, FGF, and BMP regulation using standard RT-PCR techniques. Additional snouts were processed for histology and immunohistochemistry. Untreated mouse snouts of identical age were used as controls. RESULTS: Significant upregulation of MMP8 was observed at 2 months, and MMP1a, MMP7, MMP8, and MMP12 were all significantly upregulated at 3 months. FGF3 was significantly upregulated at 3 weeks and 3 months, and FGF5, FGF6, and FGF8 were all significantly upregulated at 3 months. BMP8b and BMP9 were significantly upregulated at 3 months. Histologic analysis revealed mucosal, stromal, and mucin gland hypertrophy, increased mucin production, and metaplasia with loss of cilia. Antibody staining was strongly positive in the AF-treated group. CONCLUSIONS: Induction of CRS is associated with time-dependent changes in tissue remodeling cytokine expression occurring in conjuction with inflammatory tissue changes. Antibody staining for upregulated cytokines suggests local production within the sinonasal mucosa. Further study is required to better understand the association between BMP, FGF, and MMP regulation and tissue remodeling changes resulting from chronic inflammation. PMID- 22294480 TI - Gender representation of cancer patients in medical treatment and psychosocial survivorship research: changes over three decades. AB - BACKGROUND: Prior studies raise concern about gender bias in cancer research, including insufficient inclusion of women or men, or studying women and men differently. The 1993 National Institutes of Health Revitalization Act aimed to eliminate gender bias in medicine. To examine changes in medical and psychological literature, this study reviews gender representation in biomedical treatment studies and psychosocial survivorship studies published in a single year. METHODS: Research published in Cancer in 2007, and all empirical psychological studies about cancer published that year, provided a 15-year update to findings reported by Meyerowitz and Hart. The gender distribution and context of included articles were coded and compared with findings from 1983 and 1992. RESULTS: Across biomedical studies, 34.3% of subjects were women (vs 47% of new cancers and 48% of cancer deaths). Among men, 41.3% had sex-specific cancers (vs 12.5% [1983] and 12.3% [1992]). Among women, 46.1% had sex-specific cancers (vs 69.1% [1983] and 64.6% [1992]). Fewer women (36.8%) were represented in sex nonspecific cancer studies (vs 41.4% [1983] and 42.5% [1992]); however, fewer studies had a significant (>20%) gender disparity. Across psychosocial studies, representation of men increased to 47.9% (vs 30.4% [1983] and 29.9% [1992]). The proportion of men in studies of feelings/relationships increased to 47% (vs 22.9% [1992]); the proportion of women in studies assessing physical/functional ability increased to 58.3% (vs 45.4%). CONCLUSIONS: Women remain under-represented in sex nonspecific biomedical research, whereas men's representation in sex-specific research increased substantially. Psychosocial research trends suggest movement from research questions supporting traditional stereotypes that women feel and men act. PMID- 22294481 TI - Anaerobic utilization of pectinous substrates at extremely haloalkaline conditions by Natranaerovirga pectinivora gen. nov., sp. nov., and Natranaerovirga hydrolytica sp. nov., isolated from hypersaline soda lakes. AB - Anaerobic enrichments at pH 10, with pectin and polygalacturonates as substrates and inoculated with samples of sediments of hypersaline soda lakes from the Kulunda Steppe (Altai, Russia) demonstrated the potential for microbial pectin degradation up to soda-saturating conditions. The enrichments resulted in the isolation of six strains of obligately anaerobic fermentative bacteria, which represented a novel deep lineage within the order Clostridiales loosely associated with the family Lachnospiraceae. The isolates were rod-shaped and formed terminal round endospores. One of the striking features of the novel group is a very narrow substrate spectrum for growth, restricted to galacturonic acid and its polymers (e.g. pectin). Acetate and formate were the final fermentation products. Growth was possible in a pH range from 8 to 10.5, with an optimum at pH 9.5-10, and in a salinity range from 0.2 to 3.5 M Na(+). On the basis of unique phenotypic properties and distinct phylogeny, the pectinolytic isolates are proposed to be assigned to a new genus Natranaerovirga with two species N. hydrolytica (APP2(T)=DSM24176(T)=UNIQEM U806(T)) and N. pectinivora (AP3(T)=DSM24629(T)=UNIQEM U805(T)). PMID- 22294482 TI - Production of human tissue-engineered skin trilayer on a plasma-based hypodermis. AB - Full thickness wounds require a dermal component to achieve functional permanent skin restoration. Currently available tissue-engineered skin substitutes lack a subcutaneous fat layer that would functionally contribute some of the mechanical and thermoregulatory properties of normal skin. To generate a trilayer engineered skin equivalent, we included bone marrow mesenchymal (BM-MSC) or adipose tissue derived (ASC) stromal cells in a human plasma hydrogel exposed to adipogenic clues for three weeks. Approximately half of the cells differentiated under these conditions into mature adipocytes that survived for two years in culture with minimal medium change. In vitro generation of bona fide fully differentiated adipocytes was assessed by leptin secretion and ultrastructurally demonstrated through semithin to ultrathin sectioning and lipid staining with osmium tetroxide. Furthermore, presence of BM-MSCs or ASCs within the subcutaneous layer contributed to the epidermal differentiation program, with more proliferating basal cells depositing basal membrane proteins and differentiating into mature keratinocytes that were able to generate a pluristratified epithelium. In conclusion, we engineered a fully differentiated human skin trilayer that could present multiple applications such as use for in vitro drug absorption tests and regenerative therapies. PMID- 22294483 TI - Severe fetal and neonatal hemolytic anemia due to a 198 kb deletion removing the complete beta-globin gene cluster. AB - Fetal and neonatal hemolytic anemia can be caused by (gammadeltabeta)(0) thalassemia deletions of the beta-globin gene cluster. Many of these deletions have not been well characterized, and diagnostic tests are not readily available, thus hampering carrier detection, family counseling, and antenatal diagnosis. We report and define a 198 kb deletion removing the entire beta-globin gene cluster, which was found in members of a multigeneration family of Irish/Scottish descent. The proband had life-threatening fetal and neonatal hemolytic anemia which subsided by 1 year of age. PMID- 22294484 TI - Kinetic analysis of 18F-FLT PET in lung tumors. PMID- 22294486 TI - Risk factors of anxiety and depression in inflammatory bowel disease. AB - BACKGROUND: Little is known in inflammatory bowel disease (IBD) regarding risk factors for psychological distress. The aim of this work was to study the disease characteristics and socioeconomic factors associated with anxiety and depression in IBD. METHODS: From December 2008 to June 2009, 1663 patients with IBD (1450 were members of the Association Francois Aupetit, French association of IBD patients) answered a questionnaire about psychological and socioeconomic factors and adherence to treatment. In this study we focused the analysis on the characteristics of IBD (type, location, severity, treatment) and socioeconomic factors (professional, educational, and marital status and Evaluation of Precarity and Inequalities in Health Examination Centers [EPICES] score of socioeconomic deprivation; score established in medical centers in France; http://www.cetaf.asso.fr) associated with depression and anxiety. Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale. Comparison between groups according to the existence of depression or anxiety was carried out using univariate and multivariate analysis. RESULTS: In all, 181 patients (11%) were depressed; 689 patients (41%) were anxious. By multivariate analysis, factors associated with anxiety were: severe disease (P = 0.04), flares (P = 0.05), nonadherence to treatment (P = 0.03), disabled or unemployed status (P = 0.002), and socioeconomic deprivation (P < 0.0001). Factors associated with depression were: age (P = 0.004), flares (P = 0.03), disabled or unemployed status (P = 0.03), and socioeconomic deprivation (P < 0.0001). CONCLUSIONS: In this large cohort of IBD patients, risk factors for anxiety and depression were severe and active disease and socioeconomic deprivation. Psychological interventions would be useful when these factors are identified. PMID- 22294487 TI - Estimation of tamoxifen metabolite concentrations in the blood of breast cancer patients through CYP2D6 genotype activity score. AB - Tamoxifen, a prodrug used for adjuvant breast cancer therapy, requires conversion to the active metabolite endoxifen through CYP 2D6. We aimed to construct an algorithm to predict endoxifen concentrations based on a patient's CYP 2D6 genotype, demographic factors, and co-medication use. Eighty-eight women enrolled in the UCSF TamGen II study and 81 women enrolled in a prospective study at Dana Farber Cancer Institute were included in this analysis. All the women had been on tamoxifen for at least 3 months before blood collection. Demographic information included the patient's age, race/ethnicity, body mass index (where available), and self-reported and measured medications and herbals that affect 2D6 activity. DNA was extracted and genotyped for 2D6 (Amplichip, Roche Diagnostics). An activity score was calculated based on genotypes and adjusted for use of medications known to inhibit 2D6. Serum was tested for tamoxifen and metabolite concentrations and for the presence of drugs by liquid chromatography/mass spectrometry. Univariate and multivariate regression analysis were computed for age, body mass index, ethnicity, and adjusted activity score to predict tamoxifen metabolite concentrations in the training data-set of UCSF patients, and the resulting algorithm was validated in the Dana-Farber patients. For the training set, the correlation coefficient (r2) for log endoxifen and N desmethyltamoxifen:endoxifen ratio to activity score, age, and race, were 0.520 and 0.659, respectively; 0.324 and 0.567 for the validation; and 0.396 and 0.615 for both the datasets combined. An algorithm that incorporates genotype and demographic variables can be used to predict endoxifen concentrations for women on tamoxifen therapy. If endoxifen levels are confirmed to be predictive of tamoxifen benefit, then this algorithm may be helpful to determine which women warrant endoxifen testing. PMID- 22294488 TI - The miRNA-200 family and miRNA-9 exhibit differential expression in primary versus corresponding metastatic tissue in breast cancer. AB - Metastases are the major cause of cancer-related deaths, but the mechanisms of the metastatic process remain poorly understood. In recent years, the involvement of microRNAs (miRNAs) in cancer has become apparent, and the objective of this study was to identify miRNAs associated with breast cancer progression. Global miRNA expression profiling was performed on 47 tumor samples from 14 patients with paired samples from primary breast tumors and corresponding lymph node and distant metastases using LNA-enhanced miRNA microarrays. The identified miRNA expression alterations were validated by real-time PCR, and tissue distribution of the miRNAs was visualized by in situ hybridization. The patients, in which the miRNA profile of the primary tumor and corresponding distant metastasis clustered in the unsupervised cluster analysis, showed significantly shorter intervals between the diagnosis of the primary tumor and distant metastasis (median 1.6 years) compared to those that did not cluster (median 11.3 years) (p<0.003). Fifteen miRNAs were identified that were significantly differentially expressed between primary tumors and corresponding distant metastases, including miR-9, miR 219-5p and four of the five members of the miR-200 family involved in epithelial mesenchymal transition. Tumor expression of miR-9 and miR-200b were confirmed using in situ hybridization, which also verified higher expression of these miRNAs in the distant metastases versus corresponding primary tumors. Our results demonstrate alterations in miRNA expression at different stages of disease progression in breast cancer, and suggest a direct involvement of the miR-200 family and miR-9 in the metastatic process. PMID- 22294489 TI - Eliminating side excitations in PROPELLER-based 2D-selective RF excitations. AB - Recently, spatially two-dimensional selective radiofrequency excitations based on the PROPELLER trajectory have been presented and were applied to minimize partial volume effects in single-voxel MR spectroscopy. Thereby, residual side excitations appeared due to limitations of the Voronoi diagram that was used to consider the nonconstant sampling density, and trajectory distortions caused by eddy currents varying between the differently rotated blades. In this extension, one of the refocusing radiofrequency pulses of a PRESS-based pulse sequence is applied in the blip direction of each segment to eliminate the side excitations. This corresponds to an infinitely dense sampling of the blade and the required sampling density correction can easily be calculated. Thus, signal contributions from outside the desired region-of-interest are completely avoided. The feasibility of this approach to acquire single-voxel MR spectra of anatomically defined regions-of-interest is demonstrated in the human brain in vivo on a 3T whole-body MR system. PMID- 22294490 TI - Hepatoprotective effects of pycnogenol in a rat model of non-alcoholic steatohepatitis. AB - Oxidative stress is considered as a mechanism of hepatocellular injury in non alcoholic steatohepatitis (NASH). Pycnogenol (PYC) is the natural plant extract from the bark of Pinus pinaster Aiton. and has potent antioxidant activities. We studied the protective effect of PYC on excessive fat accumulation in the liver fed a methionine-choline deficient (MCD) high-fat diet for 6 weeks. Pycnogenol (10 mg/kg body weight) was orally administered for 5 weeks. At the end of the experiment, blood and liver samples were collected and assessed for effects of PYC by histopathological and biochemical analyses. Histopathological analyses of liver tissues stained with Azan-Mallory showed hepatic macrovesicular steatosis and fibrosis in MCD-fed rats. Supplementation of PYC prevented this effect. Pycnogenol treatment significantly decreased the liver triglyceride and serum alanine amino transferase levels. Our results indicated that orally administered PYC may serve to prevent NASH-induced liver damage. PMID- 22294491 TI - Mechanistic studies on a sulfoxide transfer reaction mediated by diphenyl sulfoxide/triflic anhydride. AB - Sulfoxides are frequently used in organic synthesis as chiral auxiliaries and reagents to mediate a wide variety of chemical transformations. For example, diphenyl sulfoxide and triflic anhydride can be used to activate a wide range of glycosyl donors including hemiacetals, glycals and thioglycosides. In this way, an alcohol, enol or sulfide is converted into a good leaving group for subsequent reaction with an acceptor alcohol. However, reaction of diphenyl sulfoxide and triflic anhydride with oxathiane-based thioglycosides, and other oxathianes, leads to a different process in which the thioglycoside is oxidised to a sulfoxide. This unexpected oxidation reaction is very stereoselective and proceeds under anhydrous conditions in which the diphenyl sulfoxide acts both as oxidant and as the source of the oxygen atom. Isotopic labelling experiments support a reaction mechanism that involves the formation of oxodisulfonium (S-O S) dication intermediates. These intermediates undergo oxygen-exchange reactions with other sulfoxides and also allow interconversion of axial and equatorial sulfoxides in oxathiane rings. The reversibility of the oxygen-exchange reaction suggests that the stereochemical outcome of the oxidation reaction may be under thermodynamic control, which potentially presents a novel strategy for the stereoselective synthesis of sulfoxides. PMID- 22294492 TI - Routine central neck dissection in differentiated thyroid carcinoma: a systematic review and meta-analysis. AB - OBJECTIVE/HYPOTHESIS: The role of central neck dissection (CND) remains controversial in differentiated thyroid cancer (DTC). STUDY DESIGN: Systematic review and meta-analysis. METHODS: A systematic review and meta-analysis focusing on surgical morbidities and locoregional recurrence after total thyroidectomy (TT) with CND versus TT alone was performed. RESULTS: Sixteen trials were analyzed. There was no increased risk of recurrent laryngeal nerve (RLN) injury (temporary or permanent), permanent hypocalcemia, or locoregional recurrence when CND was performed in addition to TT. Postoperative temporary hypocalcemia was more common after TT with CND than after TT alone. CONCLUSIONS: TT alone results in less surgical morbidity in the immediate postoperative period and an identical locoregional recurrence rate compared with TT plus CND. PMID- 22294493 TI - Plant growth promoting characterization of indigenous Azotobacteria isolated from soils in Iran. AB - It has been well known that the bacteria of the genus Azotobacter, in addition to the beneficial N(2)-fixing activity, are able to improve plant growth by a number of direct and indirect mechanisms. To identify this potential in indigenous azotobacteria, the efficiency of 17 isolates of Azotobacter from the rhizosphere of wheat and barley plants cultivated in salt- and/or drought-affected soils in Iran were evaluated for their ability to dissolve inorganic and organic phosphates, siderophore secretion, indole acetic acid (IAA) production; and protease, chitinase, and ACC deaminase (ACCD) activities. First, they were biochemically characterized and one isolate (strain) was identified by 16S rDNA sequencing. Eight isolates were designated as Azotobacter vinelandii and the remaining isolates were identified as A. chroococcum. All isolates hydrolyzed the organic and inorganic phosphate compounds and effectively produced IAA. Fifteen isolates produced siderophore, but only one isolate showed protease activity which is being reported for the first time in relation to Azotobacter. None of the 17 isolates was capable of producing ACCD or chitinase. However, polymerase chain reaction amplification of the ACCD coding genes, by the use of the gene specific primers, indicated that not all contain the ACCD gene. The standard screening methods with slight modifications, especially in the case of ACCD assay, were applied. The results showed that the use of specific screening methods, modified according to bacterial nutritional requirements, are the efficient methods for precise evaluation of the plant growth promoting rhizobacteria activity. PMID- 22294494 TI - Confirmation that Xq27 and Xq28 are susceptibility loci for migraine in independent pedigrees and a case-control cohort. AB - Investigations into migraine genetics have suggested that susceptibility loci exist on the X chromosome. These reports are supported by evidence that demonstrates male probands as having a higher proportion of affected first-degree relatives as well as the female preponderance of 3:1 that the disorder displays. We have previously implicated the Xq24-28 locus in migraine using two independent multigenerational Australian pedigrees that demonstrated excess allele sharing at the Xq24, Xq27 and Xq28 loci. Here, we expand this work to investigate a further six independent migraine pedigrees using 11 microsatellite markers spanning the Xq27-28 region. Furthermore, 11 candidate genes are investigated in an Australian case-control cohort consisting of 500 cases and 500 controls. Microsatellite analysis showed evidence of excess allele sharing to the Xq27 marker DXS8043 (LOD* 1.38 P00.005) in MF879 whilst a second independent pedigree showed excess allele sharing to DXS8061 at Xq28 (LOD* 1.5 P00.004). Furthermore, analysis of these key markers in a case control cohort showed significant association to migraine in females at the DXS8043 marker (T1 P00.009) and association with MO at DXS8061 (T1 P00.05). Further analysis of 11 key genes across these regions showed significant association of a three-marker risk haplotype in the NSDHL gene at Xq28 (P00.0082). The results of this study add further support to the presence of migraine susceptibility loci on chromosome Xq27 and Xq28 as well as point to potential candidate genes in the regions that warrant further investigation. PMID- 22294495 TI - Endocrine phenotype of children and adults with Fanconi anemia. AB - BACKGROUND: Features of Fanconi anemia (FA) are well known, including bone marrow failure, congenital anomalies such as radial anomalies, renal and ear anomalies, tracheo-esophageal fistula, imperforate anus, and elevated risk for cancer. We sought to further characterize the endocrine phenotype in children and adults with FA. PROCEDURE: Clinically indicated endocrine evaluation data from 120 persons with FA, including 78 children (43 female) and 42 young adults (who had achieved adult height, 19 female), were entered in an institutional review board approved database. Data were analyzed according to gender, birth weight, FA complementation group, and whether or not the patient had completed linear growth or had undergone hematopoietic cell transplant, using Wilcoxon Rank Sum or Chi square, as appropriate. RESULTS: Overall, 60% of children and 58% of adults with FA had short stature, 68% of children and 30% of adults had glucose intolerance, 61% of children and 37% of adults had mild hypothyroidism, and 40% of adults had evidence of hypogonadism (not possible to fully assess in children). In general, bone mineral density (BMD) was normal in adults, while BMD in children was normal when results were adjusted for bone size/thickness using height age. CONCLUSIONS: We have evaluated in detail children and adults with FA for their growth and endocrine function. Overall, 79% of children and adults with FA had one or more endocrine abnormality. PMID- 22294496 TI - Prevalence and determinants of allergic diseases in a Congolese population. AB - BACKGROUND: Allergic rhinitis (AR) is increasing worldwide, but little is known about AR in Africa. We aimed to establish the prevalence of AR and related allergic diseases, to classify AR according to the Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines, and to determine factors associated with allergy in Congo. METHODS: We conducted a cross-sectional clustered survey of the population of 8 randomly chosen health zones of Kinshasa. Information was collected on demographics, home environment, participant characteristics, atopic history, and allergic symptoms. Skin-prick testing (SPT) was done. RESULTS: Of 1508 screened individuals, 1412 (5-83 years of age) were interviewed and 1005 underwent SPT. Of the participants, 65.6% and 34.4% lived in urban and rural areas, respectively. Mean (+/- standard deviation [SD]) of age was 29 (+/-16) years and 52% were female. The 12-month prevalence of rhinitis, rhinoconjunctivitis, wheeze, and skin itch-rash was 30.8%, 24.4%, 15.4%, and 6.2%, respectively. Rhinoconjunctivitis and wheeze were more prevalent in urban than rural individuals. Of skin-tested respondents, 23.2% showed positive results, with mainly Dermatophagoides pteronyssinus and cockroach being involved. AR and non-AR prevalence was reported in 13.9% and 27.9%, respectively. Of AR individuals, 59.7% and 48.0% expressed moderate to severe and persistent symptoms, respectively. Independent determinants of having any allergic diseases in multivariate analysis were active smoking, presence of cockroach in home, history of atopy in siblings, personal history of atopy, using straw or herb mattress, and positive SPT responses. CONCLUSION: This study revealed a high prevalence of allergic diseases in Congolese individuals. It is important to increase awareness toward allergic disorders and to ensure adequate management. PMID- 22294497 TI - Horizontal transfer and death of a fungal secondary metabolic gene cluster. AB - A cluster composed of four structural and two regulatory genes found in several species of the fungal genus Fusarium (class Sordariomycetes) is responsible for the production of the red pigment bikaverin. We discovered that the unrelated fungus Botrytis cinerea (class Leotiomycetes) contains a cluster of five genes that is highly similar in sequence and gene order to the Fusarium bikaverin cluster. Synteny conservation, nucleotide composition, and phylogenetic analyses of the cluster genes indicate that the B. cinerea cluster was acquired via horizontal transfer from a Fusarium donor. Upon or subsequent to the transfer, the B. cinerea gene cluster became inactivated; one of the four structural genes is missing, two others are pseudogenes, and the fourth structural gene shows an accelerated rate of nonsynonymous substitutions along the B. cinerea lineage, consistent with relaxation of selective constraints. Interestingly, the bik4 regulatory gene is still intact and presumably functional, whereas bik5, which is a pathway-specific regulator, also shows a mild but significant acceleration of evolutionary rate along the B. cinerea lineage. This selective preservation of the bik4 regulator suggests that its conservation is due to its likely involvement in other non-bikaverin-related biological processes in B. cinerea. Thus, in addition to novel metabolism, horizontal transfer of wholesale metabolic gene clusters might also be contributing novel regulation. PMID- 22294498 TI - Adrenomedullin: a novel therapy for intractable ulcerative colitis. PMID- 22294499 TI - Physical activity, diabetes, and thyroid cancer risk: a pooled analysis of five prospective studies. AB - PURPOSE: Although many studies have linked obesity with increased risk of thyroid cancer, few have investigated the role of obesity-related lifestyle characteristics and medical conditions in the etiology of this disease. We examined the associations of self-reported physical activity and diabetes history with thyroid cancer risk in a large pooled analysis of prospective cohort studies. METHODS: Data from five prospective studies in the U.S. (n = 362,342 men, 312,149 women) were coded using standardized exposure, covariate, and outcome definitions. Hazard ratios (HR) and 95% confidence intervals (CI) for thyroid cancer were estimated using age as the time metric and adjusting for sex, education, race, marital status, cigarette smoking, body mass index, alcohol intake, and cohort. Effect modification by other risk factors (e.g., age, sex, and body mass index) and differences by cancer subtype (e.g., papillary, follicular) were also examined. RESULTS: Over follow-up (median = 10.5 years), 308 men and 510 women were diagnosed with a first primary thyroid cancer. Overall, subjects reporting the greatest amount of physical activity had an increased risk of the disease (HR = 1.18, 95% CI:1.00-1.39); however, this association was restricted to participants who were overweight/obese (>=25 kg/m(2); HR = 1.34, 95% CI:1.09-1.64) as opposed to normal-weight (<25 kg/m(2); HR = 0.92, 95% CI:0.69-1.22; P-interaction = 0.03). We found no overall association between self-reported history of diabetes and thyroid cancer risk (HR = 1.08, 95% CI:0.83-1.40). CONCLUSION: Neither physical inactivity nor diabetes history was associated with increased risk of thyroid cancer. While it may have been a chance finding, the possible increased risk associated with greater physical activity warrants further investigation. PMID- 22294500 TI - Measurements of T(1) -relaxation in ex vivo prostate tissue at 132 MUT. AB - The proton T(1) was measured at 132 MUT in ex vivo prostate tissue specimens from radical prostatectomies of 35 patients with prostate cancer. Each patient provided two specimens. The NMR and MRI measurements involved proton repolarization, a field of typically 150 mT and detection of the 5.6-kHz signal with a superconducting quantum interference device. Values of T(1) varied from 41 to 86 ms. Subsequently, the percentages of tissue types were determined histologically. The theoretical image contrast is quantified for each case by delta = [1 - T(1) (more cancer)/T(1) (less cancer)]. A linear fit of delta versus difference in percentage cancer yields T(1) (100% cancer)/T(1) (0% cancer) = 0.70 +/- 0.05 with correlation coefficient R(2) = 0.30. Two-dimensional T(1) maps for four specimens demonstrate variation within a single specimen. These results suggest that MR images with T(1) contrast established at ultra-low fields may discriminate prostate cancer from normal prostate tissue in vivo without a contrast agent. PMID- 22294501 TI - Photoreversible supramolecular polymerisation and hierarchical organization of hydrogen-bonded supramolecular co-polymers composed of diarylethenes and oligothiophenes. AB - Diarylethene 1 equipped with two monotopic melamine hydrogen-bonding sites and oligothiophene-functionalized ditopic cyanurate (OTCA) were mixed in a nonpolar solvent to form AA-BB-type supramolecular co-polymers (SCPs) bearing photoswitchable moieties in their main chains and extended pi systems as side chains. UV/Vis, fluorescence, dynamic light scattering (DLS), TEM, and AFM studies revealed that the two functional co-monomers formed flexible quasi-one dimensional SCPs in solution that hierarchically self-organized into helical nanofibers through H-aggregation of the oligothiophene side chains. Upon irradiating the SCPs with UV light, a transition occurred from the H-aggregated state to non-aggregated monomeric oligothiophene side chains, as shown by spectroscopic studies, which indicates the formation of small oligomeric species held together only by hydrogen-bonding interactions. TEM and AFM visualized unfolded fibrils corresponding to elongated single SCP chains formed upon removal of solvent. The helical nanofibers were regenerated upon irradiating the UV irradiated solution with visible light. These results demonstrated that the supramolecular polymerisation followed by hierarchical organization can be effectively controlled by proper supramolecular designs using diarylethenes and pi-conjugated oligomers. PMID- 22294502 TI - Health-related quality of life among children with acute lymphoblastic leukemia. AB - BACKGROUND: The objective was to quantify the health-related quality of life (HRQL) of children treated for acute lymphoblastic leukemia (ALL) and identify specific disabilities for remediation. PROCEDURE: Two types of subjects were included: ALL patients 5 plus years old in a multi-center clinical trial and general population control groups. Patients were assessed during all four major phases of active treatment and approximately 2 years after treatment. Health status and HRQL were measured using HEALTH UTILITIES INDEX(r) (HUI(r)) Mark 2 (HUI2) and Mark 3 (HUI3). HRQL scores were used to calculate quality-adjusted life years (QALYs). Excess disability rates identified attributes for remediation. RESULTS: HUI assessments (n = 749) were collected during the five phases. Mean HRQL increased from induction through the post-treatment phase (P < 0.001). There were no significant demographic or treatment effects on HRQL, except for type of asparaginase during continuation therapy (P = 0.005 for HUI2 and P = 0.007 for HUI3). Differences in mean HRQL scores between patients and controls were important (P < 0.001) during the active treatment phases but not during the post-treatment phase. Relative to controls, patients lost approximately 0.2 QALYs during active treatment. Disability was evident in mobility/ambulation, emotion, self-care and pain, and declined over time. CONCLUSIONS: Patients with ALL experienced important but declining deficits in HRQL during active treatment phases: Equivalent to losing approximately 2 months of life in perfect health. HRQL within the 2-years post-treatment phase was similar to controls. The policy challenge is to develop new treatment protocols producing fewer disabilities in mobility/ambulation, emotion, self-care, and pain without compromising survival. PMID- 22294503 TI - Persistent alternobaric vertigo at ground level. AB - We recently encountered a 15-year-old female with bilateral tympanostomy tubes who manifested persistent severe vertigo, at ground level, secondary to a unilateral middle-ear pressure of +200 mm H(2)O elicited by an obstructed tympanostomy tube in the presence of chronic nasal obstruction. We believe this is a previously unreported scenario in which closed-nose swallowing insufflated air into her middle ears, resulting in sustained positive middle-ear pressure in the ear with the obstructed tube. Swallowing, when the nose is obstructed, can result in abnormal negative or positive pressures in the middle ear, which has been termed the Toynbee phenomenon. In patients who have vertigo, the possibility that nasal obstruction and the Toynbee phenomenon are involved should be considered. PMID- 22294504 TI - Nanoparticle penetration through filter media and leakage through face seal interface of N95 filtering facepiece respirators. AB - National Institute for Occupational Safety and Health recommends the use of particulate respirators for protection against nanoparticles (<100 nm size). Protection afforded by a filtering facepiece particulate respirator is a function of the filter efficiency and the leakage through the face-to-facepiece seal. The combination of particle penetration through filter media and particle leakage through face seal and any component interfaces is considered as total inward leakage (TIL). Although the mechanisms and extent of nanoparticle penetration through filter media have been well documented, information concerning nanoparticle leakage through face seal is lacking. A previous study in our laboratory measured filter penetration and TIL for specific size particles. The results showed higher filter penetration and TIL for 50 nm size particles, i.e. the most penetrating particle size (MPPS) than for 8 and 400 nm size particles. To better understand the significance of particle penetration through filter media and through face seal leakage, this study was expanded to measure filter penetration at sealed condition and TIL with artificially introduced leaks for 20 800 nm particles at 8-40 l minute volumes for four N95 models of filtering facepiece respirators (FFRs) using a breathing manikin. Results showed that the MPPS was ~45 nm for all four respirator models. Filter penetration for 45 nm size particles was significantly (P < 0.05) higher than the values for 400 nm size particles. A consistent increase in filter penetrations for 45 and 400 nm size particles was obtained with increasing breathing minute volumes. Artificial leakage of test aerosols (mode size ~75 nm) through increasing size holes near the sealing area of FFRs showed higher TIL values for 45 nm size particles at different minute volumes, indicating that the induced leakage allows the test aerosols, regardless of particle size, inside the FFR, while filter penetration determines the TIL for different size particles. TIL values obtained for 45 nm size particles were significantly (P < 0.05) higher than the values obtained for 400 nm size particles for all four models. Models with relatively small filter penetration values showed lower TIL values than the models with higher filter penetrations at smaller leak sizes indicating the dependence of TIL values on filter penetration. When the electrostatic charge was removed, the FFRs showed a shift in the MPPS to ~150 nm with the same test aerosols (mode size ~75 nm) at different hole sizes and breathing minute volumes, confirming the interaction between filter penetration and face seal leakage processes. The shift in the MPPS from 45 to 150 nm for the charge removed filters indicates that mechanical filters may perform better against nanoparticles than electrostatic filters rated for the same filter efficiency. The results suggest that among the different size particles that enter inside the N95 respirators, relatively high concentration of the MPPS particles in the breathing zone of respirators can be expected in workplaces with high concentration of nanoparticles. Overall, the data obtained in the study suggest that good fitting respirators with lower filter penetration values would provide better protection against nanoparticles. PMID- 22294505 TI - Thermal burden of N95 filtering facepiece respirators. AB - Increased thermal perceptions that affect comfort are a leading reason for intolerance to wearing respiratory protective equipment. Despite their popularity and use for decades, relatively little is known about the thermal burden imposed by the use of N95 filtering facepiece respirators (FFR) at normal work rates. Twenty healthy subjects exercised at a low-moderate work rate for 1 and 2 h while wearing four models of N95 FFR (two with an exhalation valve) as core and skin temperatures were monitored wirelessly. N95 FFR use resulted in non-significant minimal increases in core temperature and uncovered facial skin (cheek) temperatures. Facial skin temperature under the FFR was significantly increased over baseline values (P < 0.001). Wearing N95 FFR for up to 2 h at a low-moderate work rate does not impose a significant thermal burden on core temperature and uncovered facial skin temperature but significantly increases the temperature of the facial skin that is covered by the FFR. Perceptions of increased body heat when wearing N95 FFR under the test conditions are likely not due to effects on core temperature but may relate more to warming of the facial skin covered by the respirator and warming of the inspired air. PMID- 22294506 TI - Microbial and histopathologic considerations in the use of mouse models of inflammatory bowel diseases. AB - Mouse models provide powerful tools to investigate disease mechanisms and are widely used in inflammatory bowel disease research. However, it is common for reports of mouse model studies to lack potentially important information about the microbial status of the mice and the method used to evaluate disease expression for statistical analysis. For example, it is common practice to state that the mice were housed under specific pathogen-free conditions but provide no further information regarding the presence or absence of organisms such as Helicobacter spp. that are known or likely to affect disease expression, thus omitting information potentially important to the expected phenotype of the mice and their responses to experimental manipulation. We therefore encourage authors to use such terms as "conventional" and "specific pathogen-free" precisely, to state the agents from which the mice are represented to be free, and to provide a brief description of the health monitoring protocol. Descriptions of histopathologic methods used to evaluate colitis in mouse models also often do not include sufficient detail to allow readers to understand and evaluate the methods; in addition, the lesions commonly are shown in photomicrographs that are too small and of too low resolution to be interpreted. Inasmuch as such methods are often the major or only source of data upon which conclusions regarding genotype or experimental treatment effects are based, the method employed should be fully described, and photomicrographs should be of adequate size and resolution to allow independent assessment. PMID- 22294507 TI - Comparison of outcomes of homeless female and male veterans in transitional housing. AB - Homelessness among female veterans is of national concern, but there have been few studies of how they differ from male veterans or whether they have different outcomes. This study compared 59 female and 1,181 male participants in a multi site study of three VA-funded transitional housing programs over a 1-year period following completion of an episode of treatment. At baseline, female participants were younger, reported more psychiatric symptoms, had shorter histories of homelessness,were less likely to have substance use disorders, and were less likely to be working than males. After controlling for these baseline differences, there were no overall gender differences in outcomes measures of housing, employment,substance use, physical and mental health, or quality of life. These results suggest homeless female veterans have different characteristics than male veterans, but benefit equally from transitional housing. PMID- 22294508 TI - Random sampling for a mental health survey in a deprived multi-ethnic area of Berlin. AB - The aim of the study was to assess the response to random sampling for a mental health survey in a deprived multi-ethnic area of Berlin, Germany, with a large Turkish-speaking population. A random list from the registration office with 1,000 persons stratified by age and gender was retrieved from the population registry and these persons were contacted using a three-stage design including written information, telephone calls and personal contact at home. A female bilingual interviewer contacted persons with Turkish names. Of the persons on the list, 202 were not living in the area, one was deceased, 502 did not respond. Of the 295 responders, 152 explicitly refused(51.5%) to participate. We retained a sample of 143 participants(48.5%) representing the rate of multi-ethnicity in the area (52.1% migrants in the sample vs. 53.5% in the population). Turkish migrants were over-represented(28.9% in the sample vs. 18.6% in the population). Polish migrants (2.1 vs. 5.3% in the population) and persons from the former Yugoslavia (1.4 vs. 4.8% in the population)were under-represented. Bilingual contact procedures can improve the response rates of the most common migrant populations to random sampling if migrants of the same origin gate the contact. High non contact and non-response rates for migrant and non-migrant populations in deprived urban areas remain a challenge for obtaining representative random samples. PMID- 22294509 TI - The acceptability and efficacy of a group cognitive behavioural therapy programme in a community mental health setting. AB - This paper presents data on a patient evaluation of a group cognitive behavioural therapy programme in an applied setting and its efficacy for reducing generalised anxiety and or depression, and distress. Patients (n=14) participated in one of two 8-week group cognitive behavioural therapy programmes for generalised anxiety or depression, within a mental health service. Patients' perceptions of the programme were collected via an evaluation questionnaire, and data on clinical outcomes were sourced from patients' case notes. Most patients who were invited to participate in the programme (n=14 of 17), and their evaluations were generally favourable. Almost all participants (93%) indicated that the programme either met or exceeded their expectations. The clinical outcomes of the intervention were similar to those found in efficacy studies reported in the published literature (approximately half to threequarters of one standard deviation improvement in anxiety, depression, and distress scores). PMID- 22294510 TI - The factors influencing decision making on children's psychiatric hospitalization: a retrospective chart review. AB - Indications and criteria for psychiatric hospitalization(PH) continue to be questioned and assessed. We investigated the major clinical criteria affecting child psychiatrists' decision to recommend hospitalization. Records of 80 children (aged 7-13 years) treated at the Geha Mental Health Center's (GMHC's) outpatient clinic were reviewed.The patients' files were divided into three groups: admitted to PH (n = 20), candidates for PH who, ultimately, were not hospitalized (n = 20) and 40 patients for whom PH was nota consideration. Three groups of criteria were chosen to evaluate the decision for PH (type and severity of the psychiatric disorders, family's level of distress and parental capacity to contain the child). These criteria were rated quantitatively by using CGI-S. Highly significant inverse association was found between the level of parental capacity to contain the child and the decision to hospitalize in a psychiatric pediatric institution. The correlations between severity of the psychiatric disorders and family's level of distress was also found significant, but to a lesser extent.Parental capacity to contain the child, with its various components, is a major factor in the decision making process,when referring children to PH. This is the first study,demonstrating a strong association between parental-capacity components and the rate of hospitalization. PMID- 22294511 TI - Metabolic MR imaging of regional triglyceride and creatine content in the human heart. AB - An optimized echo-planar spectroscopic imaging sequence is proposed to facilitate spatial mapping of triglyceride and total creatine content in the human heart. The sequence integrates local-look field of view reduction, cardiac and respiratory gating, and dedicated reconstruction steps to account for gradient channel delays, field inhomogeneity, and phase incoherence due to residual motion. The technique is demonstrated in 12 volunteers in comparison to single voxel point-resolved spectroscopy in the septal wall at 1.5 T. Triglyceride-to water and total creatine-to-water ratios derived from echo-planar spectroscopic imaging (0.48 +/- 0.18% and 0.06 +/- 0.03%) and point-resolved spectroscopy (0.52 +/- 0.17% and 0.07 +/- 0.02%) were found to agree well. In the septal region, intraclass correlation coefficients ranging from 0.67 to 0.72 were estimated. A relatively weak agreement (intraclass correlation coefficients: 0.34 and 0.52) was found for sectors in the lateral wall due to field gradients induced by the posterior vein and limited sensitivity of the receive coil array in this area. On the basis of the findings, it is concluded that fast spectroscopic imaging of both cardiac triglyceride and total creatine content is feasible. Shimming and sensitivity challenges in the lateral region remain, however, to be addressed. PMID- 22294513 TI - Light-harvesting hybrid assemblies. AB - Light-harvesting hybrids have gained much importance as they are considered as potential mimics for photosynthetic systems. In this Concept article we introduce the design concepts involved in the building up of light-harvesting hybrids; these resemble the well-studied organic-based assemblies for energy transfer. We have structured this article into three parts based on the strategies adopted in the synthesis of hybrid assemblies, as covalent, semicovalent, and noncovalent procedures. Furthermore, the properties and structural features of the hybrids and analogous organic assemblies are compared. We also emphasize the challenges involved in the processability of these hybrid materials for device applications and present our views and results to address this issue through the design of soft-hybrids by a solution-state, noncovalent, self-assembly process. PMID- 22294514 TI - Scientific attributes of a researcher and member of The Triological Society. AB - This presidential address discusses the comments from the first Mayo Clinic's Chair, Harold Lille, MD, regarding different contributions by members of The Triological Society in his 1939 presidential address. It then goes on to discuss scientific research attributes expected of members of the Society that were gleaned from a fusion of Dr. Berke's notions with what other famous researchers, inventors, and philosophers have said about aspects of research. The areas covered include research motivation, the process of research, the scientific method, imagination, intuition and luck, questioning in science, tenacity, ideas, and knowledge. In summary, the following are the expected attributes of a researcher and member of the Society. The individual should enjoy the creation of new knowledge and appreciate the mysteries of life and the joy of discoveries. He or she should be a staunch supporter of the scientific method, but should also understand that every researcher is a professional amateur, and that the process of research is often fraught with blind alleys and incorrect ideas and assumptions, and that ultimately hypotheses must be substantiated by experiments. A researcher must exhibit imagination and intuition augmented by tenacity and scientific questioning. Finally, he or she should recognize that chance favors the prepared mind, and always be on the lookout for novel ideas framed by a comprehension of existing knowledge, not just in one domain but across a broad horizon of disciplines. PMID- 22294512 TI - Effect of hydroxyurea treatment on renal function parameters: results from the multi-center placebo-controlled BABY HUG clinical trial for infants with sickle cell anemia. AB - BACKGROUND: Children with sickle cell anemia (SCA) often develop hyposthenuria and renal hyperfiltration at an early age, possibly contributing to the glomerular injury and renal insufficiency commonly seen later in life. The Phase III randomized double-blinded Clinical Trial of Hydroxyurea in Infants with SCA (BABY HUG) tested the hypothesis that hydroxyurea can prevent kidney dysfunction by reducing hyperfiltration. PROCEDURE: 193 infants with SCA (mean age 13.8 months) received hydroxyurea 20 mg/kg/day or placebo for 24 months. (99m) Tc diethylenetriaminepentaacetic acid (DTPA) clearance, serum creatinine, serum cystatin C, urinalysis, serum and urine osmolality after parent-supervised fluid deprivation, and renal ultrasonography were obtained at baseline and at exit to measure treatment effects on renal function. RESULTS: At exit children treated with hydroxyurea had significantly higher urine osmolality (mean 495 mOsm/kg H(2) O compared to 452 in the placebo group, P = 0.007) and a larger percentage of subjects taking hydroxyurea achieved urine osmolality >500 mOsm/kg H(2) O. Moreover, children treated with hydroxyurea had smaller renal volumes (P = 0.007). DTPA-derived glomerular filtration rate (GFR) was not significantly different between the two treatment groups, but was significantly higher than published norms. GFR estimated by the Chronic Kidney Disease in Children (CKiD) Schwartz formula was the best non-invasive method to estimate GFR in these children, as it was the closest to the DTPA-derived GFR. CONCLUSION: Treatment with hydroxyurea for 24 months did not influence GFR in young children with SCA. However, hydroxyurea was associated with better urine concentrating ability and less renal enlargement, suggesting some benefit to renal function. PMID- 22294515 TI - Clinical predictors at diagnosis of disabling pediatric Crohn's disease. AB - BACKGROUND: Identification of children with Crohn's disease (CD) at high risk of disabling disease would be invaluable in guiding initial therapy. Our study aimed to identify predictors at diagnosis of a subsequent disabling course in a population-based cohort of patients with pediatric-onset CD. METHODS: Among 537 patients with pediatric CD diagnosed at <17 years of age, 309 (57%) with 5-year follow-up were included. Clinical and demographic factors associated with subsequent disabling CD were studied. Three definitions of disabling CD were used: Saint-Antoine and Liege Hospitals' definitions and a new pediatric definition based on the presence at maximal follow-up of: 1) growth delay defined by body mass index (BMI), weight or height lower than -2 SD Z score; and 2) at least one intestinal resection or two anal interventions. Predictors were determined using multivariate analyses and their accuracy using the kappa method considering a relevant value >= 0.6. RESULTS: According to the Saint-Antoine definition, the rate of disabling CD was 77% and predictors were complicated behavior and L1 location. According to the Liege definition, the rate was 37% and predictors included behavior, upper gastrointestinal disease, and extraintestinal manifestations. According to the pediatric definition, the rate of disabling CD was 15%, and predictors included complicated behavior, age <14, and growth delay at diagnosis. Kappa values for each combination of predictors were, respectively, 0.2, 0.3, and 0.2 and were nonrelevant. CONCLUSIONS: Clinical parameters at diagnosis are insufficient to predict a disabling course of pediatric CD. More complex models including serological and genetic biomarkers should be tested. PMID- 22294516 TI - Surface antigenic profiling of stem cells from human omentum fat in comparison with subcutaneous fat and bone marrow. AB - Omentum fat derived stem cells have emerged as an alternative and accessible therapeutic tool in recent years in contrast to the existing persuasive sources of stem cells, bone marrow and subcutaneous adipose tissue. However, there has been a scanty citation on human omentum fat derived stem cells. Furthermore, identification of specific cell surface markers among aforesaid sources is still controversial. In lieu of this existing perplexity, the current research work aims at signifying omentum fat as a ground-breaking source of stem cells by surface antigenic profiling of stem cell population. In this study, we examined and compared the profiling of cell surface antigenic expressions of hematopoietic stem cells, mesenchymal stem cells, cell adhesion molecules and other unique markers such as ABCG2, ALDH and CD 117 in whole cell population of human omentum fat, subcutaneous fat and bone marrow. The phenotypic characterization through flowcytometry revealed the positive expressions of CD 34, CD 45, CD 133, HLADR, CD 90, CD 105, CD 73, CD 29, CD 13, CD 44, CD 54, CD 31, ALDH and CD 117 in all sources. The similarities between the phenotypic expressions of omentum fat derived stem cells to that of subcutaneous fat and bone marrow substantiates that identification of ultimate source for curative therapeutics is arduous to assess. Nevertheless, these results support the potential therapeutic application of omentum fat derived stem cells. PMID- 22294517 TI - Simple baseline correction for 1H MRSI data of the prostate. AB - Proton magnetic resonance spectroscopic imaging of the prostate can detect and localise tumour tissue in patients with prostate cancer. Pattern recognition methods have the potential to discriminate tumour from normal tissue using the spectral patterns of magnetic resonance spectroscopic imaging data thus providing a powerful tool for diagnosis and monitoring treatment of prostate cancer. Prostate magnetic resonance spectroscopic imaging data acquisition has been optimized for a flat baseline, including a long echo time and the use of water and fat suppression pulses. Despite this acquisition method, lipid resonances may still occur particularly at the margins of the prostate. Correcting the baseline by removing lipid artifacts is, therefore, a necessary processing step. We propose a simple baseline correction method for prostate magnetic resonance spectroscopic imaging through subtraction of a single simulated-lorentzian resonance. This method is shown to restore flat baselines to a test set of spectra and compares favorably with a state-space modeling approach. PMID- 22294518 TI - Microevolution of extensively drug-resistant tuberculosis in Russia. AB - Extensively drug-resistant (XDR) tuberculosis (TB), which is resistant to both first- and second-line antibiotics, is an escalating problem, particularly in the Russian Federation. Molecular fingerprinting of 2348 Mycobacterium tuberculosis isolates collected in Samara Oblast, Russia, revealed that 72% belonged to the Beijing lineage, a genotype associated with enhanced acquisition of drug resistance and increased virulence. Whole-genome sequencing of 34 Samaran isolates, plus 25 isolates representing global M. tuberculosis complex diversity, revealed that Beijing isolates originating in Eastern Europe formed a monophyletic group. Homoplasic polymorphisms within this clade were almost invariably associated with antibiotic resistance, indicating that the evolution of this population is primarily driven by drug therapy. Resistance genotypes showed a strong correlation with drug susceptibility phenotypes. A novel homoplasic mutation in rpoC, found only in isolates carrying a common rpoB rifampicin-resistance mutation, may play a role in fitness compensation. Most multidrug-resistant (MDR) isolates also had mutations in the promoter of a virulence gene, eis, which increase its expression and confer kanamycin resistance. Kanamycin therapy may thus select for mutants with increased virulence, helping preserve bacterial fitness and promoting transmission of drug resistant TB strains. The East European clade was dominated by two MDR clusters, each disseminated across Samara. Polymorphisms conferring fluoroquinolone resistance were independently acquired multiple times within each cluster, indicating that XDR TB is currently not widely transmitted. PMID- 22294519 TI - A photo-induced, and chemical-driven, smart-gating nanochannel. PMID- 22294521 TI - Myrislignan attenuates lipopolysaccharide-induced inflammation reaction in murine macrophage cells through inhibition of NF-kappaB signalling pathway activation. AB - Myrislignan is a new kind of lignan isolated from Myristica fragrans Houtt. Its antiinflammatory effects have not yet been reported. In the present study, the antiinflammatory effects and the underlying mechanisms of myrislignan in lipopolysaccharide (LPS)-induced inflammation in murine RAW 264.7 macrophage cells were investigated. Myrislignan significantly inhibited LPS-induced production of nitric oxide (NO) in a dose-dependent manner. It inhibited mRNA expression and release of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha). This compound significantly inhibited mRNA and protein expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) dose-dependently in LPS-stimulated macrophage cells. Further study showed that myrislignan decreased the cytoplasmic loss of inhibitor kappaB-alpha (IkappaB-alpha) protein and the translocation of NF-kappaB from cytoplasm to the nucleus. Our results suggest that myrislignan may exert its antiinflammatory effects in LPS-stimulated macrophages cells by inhibiting the NF-kappaB signalling pathway activation. PMID- 22294520 TI - Autophagy regulates lipolysis and cell survival through lipid droplet degradation in androgen-sensitive prostate cancer cells. AB - BACKGROUND: Androgen deprivation therapy, one of the standard treatments for prostate cancer (PCa) induces apoptosis, as well as autophagy in androgen responsive PCa cells. As autophagy can promote either cell survival or death, it is important to understand its role in PCa treatment. The objective of this study was to elucidate the function of autophagy in lipid droplet (LD) homeostasis and survival in androgen-sensitive PCa cells. METHODS: To produce androgen deprivation, charcoal filtered serum or the androgen inhibitor casodex were used in LNCaP and LAPC4 cells. Autophagy was monitored by immunofluorescence/confocal microscopy and immunoblot analysis. Levels of intracellular LDs and triacyglycerols after the inhibition of autophagy by 3-methyladenine, bafilomycin A(1) , or si-ATG5 were quantified by three independent methods, Oil Red O staining, triacyglycerols lipase assay, and nuclear magnetic resonance. RESULTS: Androgen deprivation induced autophagy and the depletion of LDs in both of the androgen-sensitive PCa cell lines examined, whereas the blockage of autophagy by pharmacological or genetic means inhibited LD degradation and therefore lipolysis and cell growth. In addition, under androgen deprivation, increased colocalization of LDs and autophagic vesicles was observed in LNCaP cells, which can be further enhanced by blocking the autophagic flux. CONCLUSION: Autophagy mediates LD degradation and lipolysis in androgen-sensitive PCa cells during androgen deprivation which aids the survival of PCa cells during hormone therapy. PMID- 22294522 TI - NKG2D/Ligand dysregulation and functional alteration of innate immunity cell populations in pediatric IBD. AB - BACKGROUND: Dysregulated innate immune responses play an important role in inflammatory bowel disease (IBD). NKG2D innate immunity receptor is a major sensor of tissue damage that, by recognizing multiple stress-induced, cell associated ligands (MIC-A/B and ULBP1-5), potentiates the effector functions of "innate-like" (gamma/delta TcR+, and natural killer receptor+ [NKR+]) T-cell populations. We analyzed the representivity, NKG2D/ligand expression pattern, and functional ability of the major innate immunity cell populations in pediatric IBD patients. METHODS: We analyzed 41 Crohn's disease (CD) patients, 33 ulcerative colitis (UC) patients, and 51 age-matched non-IBD controls. The expression of NKG2D and its ligands, interferon-gamma (IFN-gamma) production, and cytotoxic granule release were assessed by immunostaining and multiparameter cytofluorimetric analysis on circulating and mucosal mononuclear subsets; the inflammatory infiltrate was also characterized by immunohistochemistry. RESULTS: The expression pattern of NKG2D receptor and its ligands on mucosal and circulating innate immunity populations is severely disturbed in IBD; NKG2D and ligands are upregulated on immune infiltrate in both CD and UC active lesions; receptor/ligand upregulation also occurs on circulating leukocyte populations, where it depends on both disease activity and type (UC vs. CD). Finally, the frequency and effector capability of peripheral blood "innate-like" T-cell populations are also altered in IBD patients. CONCLUSIONS: The circulating and mucosal innate immunity compartment is phenotypically and functionally altered in pediatric IBD; some alterations may represent a distinctive feature of the pediatric disease condition. The disturbance of NKG2D/ligand pathway may play a role in sustaining immune activation which leads to chronic inflammatory tissue damage. PMID- 22294524 TI - Massively parallel bacterial and yeast suspension culture on a chip. PMID- 22294525 TI - Social Interaction Style of Children and Adolescents with High-Functioning Autism Spectrum Disorder. AB - Qualitative differences in social interaction style exist within the autism spectrum. In this study we examined whether these differences are associated with (1) the severity of autistic symptoms and comorbid disruptive behavior problems, (2) the child's psycho-social health, and (3) executive functioning and perspective taking skills. The social interaction style of 156 children and adolescents (6-19 years) with high-functioning autism spectrum disorder (HFASD) was determined with the Wing Subgroups Questionnaire. An active-but-odd social interaction style was positively associated with symptoms of autism, attention deficit and hyperactivity. Furthermore, an active-but-odd social interaction style was negatively associated with children's psycho-social health and positively with executive functioning problems. Social interaction style explains part of the heterogeneity among children with HFASD. PMID- 22294526 TI - Clinical activity of sorafenib in patients with advanced gastrointestinal stromal tumor bearing PDGFRA exon 18 mutation: a case series. PMID- 22294527 TI - To PET or not to PET? That is the question. Staging in anal cancer. AB - BACKGROUND: Anal cancer is a rare tumour accounting for ~2% of all colorectal cancers between 1997 and 2000 in the UK. Staging is still dominated by DRE (digital rectal examination), computed tomography (CT) and magnetic resonance imaging (MRI) imaging. The role of PET as a definitive modality is still emerging and there are relatively few adequate studies in the literature. METHODS: We looked at patients treated radically for anal cancer at Mount Vernon Cancer Centre (UK) between 2009 and 2010. Eighty-eight patients underwent treatment according to data-based coding records of which 46 had positron emission tomography (PET)/CT scans. Notes were unavailable for three patients. We compared staging following conventional modalities (DRE, MRI and CT) and PET/CT scans for these 43 patients. RESULTS: In 18 patients, the PET/CT stage differed from MRI. PET/CT altered the stage in 42% of patients but changes in subsequent management were not implemented. CONCLUSIONS: Our data show that PET/CT does alter staging in a significant number of cases although it did not lead to change in management under the current guidelines. Furthermore, there is agreement that PET/CT shows greater sensitivity for detection of lymph nodes and our study has demonstrated a distinct trend towards upstaging of anal cancer with PET/CT. PMID- 22294528 TI - Fast metabolite mapping in the pig heart after injection of hyperpolarized 13C pyruvate with low-flip angle balanced steady-state free precession imaging. AB - The conversion of hyperpolarized (13)C pyruvate to metabolic products in the Krebs cycle provides valuable information about the metabolic status and the viability of the myocardium. Therefore, imaging methods must be able to spectrally discriminate different (13)C metabolites. However, the requirement for spectral selectivity conflicts with the demands for rapid image acquisition and high spatial resolution in cardiac imaging. In this work, the feasibility of a balanced steady state free precession sequence with low flip angles was investigated in the pig heart after injection of hyperpolarized (13)C(1) pyruvate. Using cardiac gating, it was possible to acquire (13)C-bicarbonate images within a single heartbeat (acquisition time 150 ms) without destroying the substrate signal from the hyperpolarized pyruvate. Therefore, the technique may be useful in dynamic studies of cardiac metabolism. PMID- 22294529 TI - Buddy-balloon technique for final kissing-balloon dilatation after crush stenting of the left main coronary artery. AB - BACKGROUND: Crush stenting mandates a final kissing-balloon technique (KBT) for a better clinical outcome; however, recrossing the 2 overlapping stent struts with the balloon catheter is technically challenging. OBJECTIVES: The efficacy of the buddy-balloon technique for facilitating completion of the final KBT during crush stenting of the left main coronary artery (LMCA) was evaluated. METHODS: The records of 38 consecutive patients who underwent crush stenting for a lesion in the distal LMCA from January 2005 to December 2009 were retrospectively reviewed. RESULTS: In 23 of the 38 patients, recrossing the balloon catheter to the left circumflex artery (LCX) was difficult, even with appropriate backup support from the guiding catheter. To enhance recrossing of the balloon catheter, the buddy balloon technique was used, which resulted in the successful completion of the final KBT in 21 patients (91.3%). For the 2 patients in whom the technique was unsuccessful, the final KBT was subsequently achieved by performing the buddy balloon technique in the LCX using a 1.5 mm balloon catheter. The overall success rate of the final KBT was 100%. One year after the procedure, target lesion revascularization (TLR) rate of these 23 cases showed no significant difference when compared with the TLR rate of patients for whom this technique was not needed. CONCLUSION: The buddy-balloon technique is a suitable option when used in the context of crush stenting in patients with lesions of the distal LMCA. PMID- 22294530 TI - Effect of remote ischemic preconditioning on myocardial and renal injury: meta analysis of randomized controlled trials. AB - OBJECTIVES: The purpose of this study was to assess the effect of remote ischemic precondition (RIPC) on the incidence of myocardial and renal injury in patients undergoing cardiovascular interventions as measured by biomarkers. Clinical data were pooled to evaluate the usefulness of RIPC to benefit clinical outcomes. BACKGROUND: Debate exists regarding the merit of using RIPC for patients undergoing cardiovascular interventions. METHODS: Systematic review and meta analysis of prospective randomized clinical trials of patients undergoing cardiovascular interventions who received RIPC versus control were performed. Two independent reviewers selected articles from MEDLINE, EMBASE, SCOPUS, Cochrane, ISI Web of Science, and BIREME, and through hand search of relevant reviews and meeting abstracts upon agreement. Surrogate markers of myocardial (troponin T or I and CK-MB) and renal (serum creatinine) injury for primary outcomes were abstracted. RESULTS: Final pooled analysis from 17 clinical trials showed significant heterogeneity of results and no relevant publication bias. Patients receiving RIPC had lower levels of markers of myocardial injury in the first few days after surgery (standardized mean difference [SMD], 0.54; 95% confidence interval [CI], -1.01 to -0.08; P=.01) with highly heterogeneous results (I2 = 93%). A lower incidence of perioperative myocardial infarction (7.9% RIPC vs 13.9% placebo; RR, 0.56; 95% CI, 0.37-0.84; P=.005; I2 = 0%) was also noted. In patients undergoing abdominal aortic aneurysm repair, RIPC when compared to control also decreased renal injury (SMD, 0.28; 95% CI, -0.49 to -0.08; P=.007; I2 = 51%). CONCLUSIONS: RIPC appears to be associated with a favorable effect on serological markers of myocardial and renal injury during cardiovascular interventions. Larger trials should be conducted to substantiate this initial impression. PMID- 22294531 TI - Use of an objective tool to assess platelet inhibition prior to off-pump coronary surgery to reduce blood usage. AB - BACKGROUND: The current standard of care is to delay coronary surgery 5-7 days after clopidogrel exposure to prevent bleeding complications. We sought to determine the utility of an objective tool (ie, the VerifyNow assay) to measure platelet inhibition (PI) in patients receiving preoperative clopidogrel prior to off-pump coronary artery bypass grafting surgery (OPCABG). PATIENTS AND METHODS: Between June 2007 and July 2009, a total of 482 isolated OPCABG procedures were performed at our institution. In 160 patients, the VerifyNow assay results were used to determine timing of the OPCABG. These patients were compared to the remaining 322 patients. We divided the cohort into 4 subgroups: Group 1 patients (n = 205) were not taking clopidogrel; Group 2 patients (n = 117) were taking clopidogrel, but the test was not performed; Group 3 patients (n = 122) were taking clopidogrel and had a preoperative PI result of <=20%; and Group 4 patients (n = 38) had >=21% preoperative PI. RESULTS: Demographic and clinical factors were compared in all groups. The median waiting time for surgery from the last dose of clopidogrel was 6 days for the control groups and 3 days for the groups where the test was performed (P<.001). Reoperation for bleeding occurred most often in Group 4 (7.9%; P=.003). Blood utilization was lower in Group 1 (24.4%) than in Groups 2 (34.2%), 3 (40.2%), or 4 (55.3%) (P<.001). Major complications and postoperative length of stay were similar in all groups. CONCLUSIONS: Utilization of a PI tool in the preoperative assessment of OPCABG patients exposed to clopidogrel can provide valuable information to guide the timing of coronary surgery and may lead to a decrease in reoperation for bleeding and blood usage. PMID- 22294532 TI - Coronary artery bypass graft surgery in patients receiving antiplatelet therapy: can we "fine-tune" the balance of safety and efficacy? PMID- 22294533 TI - Mechanism of edge restenosis after sirolimus-eluting stent implantation. AB - OBJECTIVES: The present study evaluated the mechanism of edge restenosis after sirolimus-eluting stent (SES) implantation using serial (post-intervention and follow-up) intravascular ultrasound (IVUS) analysis. BACKGROUND: There is little information about the mechanism of edge restenosis after SES implantation. METHODS: Serial IVUS analysis was performed at 5 mm reference segments immediately proximal and distal to the SES in 25 lesions with edge restenosis. Proximal and distal reference segments were divided into 1 mm subsegments. RESULTS: Between post-intervention and follow-up IVUS studies, a decrease in external elastic membrane area was observed at the proximal edge. There was a significant increase in plaque & media area in the subsegment closest to the proximal edge. On the other hand, there was an increase in plaque & media area at the distal edge, with no change in external elastic membrane area. CONCLUSIONS: There may be different mechanisms between proximal and distal edge restenosis after SES implantation. Negative remodeling plays a major role in proximal edge restenosis. On the other hand, intimal hyperplasia may mainly contribute to distal edge restenosis. PMID- 22294534 TI - Short-term efficacy of palliative balloon aortic valvuloplasty in selected patients with high operative risk. AB - With the introduction of transcatheter aortic valve implantation (TAVI), the precise role of balloon aortic valvuloplasty (BAV) remains to be established. METHODS: Between August 2008 and November 2010, consecutive patients undergoing BAV for severe aortic stenosis (AS) in our center were enrolled. The primary endpoint was survival to hospital discharge. Secondary endpoints were 30-day survival and progression to aortic valve replacement (AVR). RESULTS: Enrolled were 64 patients (age, 82 +/- 8 years; 45% male). Treatment objectives were: symptom palliation (69%); potential AVR (23%); and facilitation of withdrawal of ventilation or non-cardiac surgery (8%). At baseline, patients had logistic EuroSCORE of 35.7 +/- 19.5, NT-proBNP of 11,195 +/- 11,694 ng/L, aortic valve area of 0.53 +/- 0.17 cm2, and peak transaortic gradient (PG) of 75.2 +/- 25.3 mm Hg. The primary endpoint of survival to hospital discharge was reached by 97% patients. The secondary endpoint of 30-day mortality occurred in 8 patients (13%). Overall, 12 patients showed clinical improvement within 1 month of BAV. Of these, 8 patients underwent AVR (TAVI in 3/8 [38%]). After multivariate adjustment, the strongest correlates for 30-day survival and progression to AVR pre-BAV were: New York Heart Association <=II, SBP >=90 mm Hg, estimated glomular filtration rate >=45 mL min-1, left ventricular ejection fraction >=45% and transaortic PG <80 mm Hg. CONCLUSION: In patients with severe AS and high operative risk, BAV has the potential to facilitate progression to TAVI in those who are technically suitable. PMID- 22294535 TI - Old dog, new tricks: redefining the role for balloon aortic valvuloplasty in the transcatheter aortic valve replacement era. PMID- 22294536 TI - Saphenous vein graft intervention: a review. AB - Saphenous vein grafts are prone to degeneration and occlusion. Vein graft disease continues to be a significant problem in maintaining long-term benefits after coronary artery bypass surgery. The neointimal hyperplasia and aggressive atherosclerosis that occur in saphenous vein grafts make interventions particularly challenging due to plaque embolization and the no-reflow phenomenon. This review discusses the pathophysiology of vein graft disease and the various percutaneous strategies that have been applied to manage vein grafts. We review the issues surrounding stent selection and various approaches to embolic protection devices. Finally, we discuss the technical steps that optimize success in treating this challenging patient subset. PMID- 22294537 TI - Transradial measurement of transvalvular pressure gradient in the setting of mechanical aortic and mitral valve prostheses using a coronary fractional flow reserve guidewire. AB - Accurate measurement of transvalvular pressure gradients is essential to comprehensively evaluate whether mechanical prosthetic valves are functioning normally. Direct measurements can be technically complicated, traditionally requiring direct, transapical puncture in the setting of both aortic and mitral mechanical valve prostheses. Very few case reports have proposed the use of guidewires indicated for coronary fractional flow reserve assessment to evaluate the transvalvular pressure gradients and hemodynamic status of patients with both aortic and mitral valve mechanical prostheses. We present one such case of a 59 year-old male with history of rheumatic heart disease and double mechanical valve replacements of the aortic and mitral valves presenting with contradictory clinical signs and noninvasive testing evidence of decompensated congestive heart failure and possible dysfunction of a mechanical, bi-leaflet aortic valve prosthesis. The use of a low-profile, intracoronary guidewire with a pressure transducer near the distal tip indicated for coronary fractional flow reserve determination proved very useful to answer this important question. Additionally, we report the first case of the use of this technology for this purpose via the radial artery access approach. PMID- 22294538 TI - Successful transradial retrieval of broken catheter fragment during transradial coronary angiography. AB - Intravascular fracture of angiographic catheters is very uncommon, but it happens. Removal of an intravascular foreign body may require surgical intervention or non-surgical retrieval necessitating additional vascular access (mostly via femoral artery). We describe a case in which the diagnostic catheter was broken. We were able to pass two guidewires (0.035-inch guidewire and 0.014 inch standard percutaneous transluminal coronary angioplasty guidewire) through the fragment. The 0.014-inch guidewire twirled, winding around the 0.035-inch wire, and the catheter fragment was retrieved successfully through the radial sheath. PMID- 22294539 TI - Successful use of glycoprotein IIb/IIIa inhibitor, heparin, and IABP during PCI in a post-neurosurgical patient with STEMI and cardiogenic shock due to very late bare-metal stent thrombosis. AB - Stent thrombosis is not unusual in a post-operative setting. Use of heparin, aspirin, clopidogrel, and glycoprotein (GP) IIb/IIIa inhibitors in this setting needs to be balanced because of the increased risk of perioperative bleeding. This is of special concern in neurosurgery, where postoperative mass effect from bleeding in a closed space is a serious risk. We describe a unique case of inferior and anterior ST-elevation myocardial infarction in cardiogenic shock during spinal surgery with acute, very late bare-metal stent (BMS) thrombosis in the left anterior descending coronary artery and simultaneous acute thrombotic occlusion of the right coronary artery, treated by primary percutaneous intervention, intra-aortic balloon pump (IABP) support and use of GP IIb/IIIa inhibitor in addition to clopidogrel, aspirin, and heparin with good surgical and cardiac outcome. This case report describes first time use of GP IIb/IIIa inhibitor and IABP with heparin, in a patient just after spinal surgery. PMID- 22294540 TI - Coronary imaging and intervention during cardiovascular collapse: use of the LUCAS mechanical CPR device in the cardiac catheterization laboratory. AB - The management of cardiac arrest during coronary angiography and intervention presents substantial challenges. Patients presenting with ST-segment elevation myocardial infarction or following resuscitation from cardiac arrest are at greatest risk and may represent a significant portion of patients in some centers. Timely and effective cardiopulmonary resuscitation (CPR), with manual chest compressions is the primary mode of support though novel circulatory assist devices may have some role. To this end, the use of mechanical compression devices provides multiple patient- and provider-level benefits. This series provides a description of the use of the LUCAS mechanical CPR device and examples of coronary imaging and intervention during mechanical CPR. PMID- 22294541 TI - An unusual complication after coronary catheterization. AB - Valvular complications after coronary catheterization are extremely rare and are seldom reported in the literature. We report a patient who experienced acute traumatic aortic regurgitation after repeated coronary transcatheter procedures. Despite clinical stabilization under medical treatment, his clinical course led to an aortic-valve replacement. PMID- 22294542 TI - Transcatheter closure of a large aortopulmonary window with severe pulmonary arterial hypertension beyond infancy. AB - A patient presented with a large aortopulmonary window and significant pulmonary hypertension, and underwent successful closure with muscular ventricular septal occluder (Shen-Zhen Lifetech Scientific Inc.) without complications in short-term follow-up. PMID- 22294543 TI - Deferring coronary stenting for myocardial bridging by fractional flow reserve and optical coherence tomography. AB - Deciding how to treat acute myocardial infarction (MI) with myocardial bridge is difficult because stent fracture and early restenosis are frequently reported. We present a 50-year-old female patient with acute MI and myocardial bridge. Optical coherence tomography (OCT) and fractional flow reserve were used to reach a decision on treatment. PMID- 22294544 TI - Novel use of a GuideLiner catheter to visualize distal LAD after LIMA anastomosis in selective coronary angiography. AB - We report a case of GuideLiner catheter use during transradial intervention for selective coronary angiography of the distal left anterior descending artery (LAD), beyond the left internal mammary artery (LIMA) anastomosis. The lesion within the LAD was located distal to the anastomosis of a very tortuous LIMA, otherwise unable to be visualized due to competitive flow from the LIMA. Stenting by way of the LIMA could not be performed due to this severe tortuosity as well. Alternatively, performance of the intervention without GuideLiner assistance would have required dual access, with injections both through the LIMA graft and the native LAD for angiography and intervention. Use of the GuideLiner served the purpose of selective LAD angiography to visualize the lesion, as well as delivery of the stent through a proximally calcified LAD. Using this single transradial route allowed the intervention to be completed, while reducing complications due to multiple access sites. PMID- 22294545 TI - Transcatheter repair of Fontan baffle stenosis and fenestration in two patients using Cook Zenith aortic endografts. AB - Patients with Fontan baffles for single ventricle may have cyanosis from right-to left shunt through leaks in the baffle or due to intentionally created fenestrations. Typically this right-to-left shunt may be addressed with catheter based occlusion devices. However, in narrowing of the Fontan baffle, placement of occluders within the Fontan baffle may additionally narrow the pathway and is therefore undesirable. We describe 2 patients with the combination of Fontan baffle stenosis and patent fenestration treated with a Zenith abdominal aortic aneurysm endograft (Cook Medical). The covered stent graft both occluded the right-to-left shunt and eliminated the baffle stenosis. Both patients have had symptomatic improvement. PMID- 22294546 TI - Usefulness of the Corsair microcatheter for treatment of complex chronic total occlusion. AB - Percutaneous coronary intervention (PCI) for the treatment of chronic total occlusion (CTO) is one of the most technically challenging areas of interventional cardiology. When CTO is combined with angulation and tortuosity of the coronary artery, the technical complexity of PCI for CTO is magnified. In this report, we describe a case of successful revascularization of a CTO lesion in the complex circumflex anatomy using a novel microcatheter (the Corsair catheter) along with an antegrade approach to facilitate guidewire passage through a proximal steep angulation and to cross the circumflex CTO lesion that was unresponsive with conventional microcatheters. PMID- 22294547 TI - Application of optical coherence tomography in the treatment of coronary bifurcation lesions. AB - Optical coherence tomography (OCT) is a novel intravascular imaging modality with excellent resolution. We report the application of OCT in 3 coronary bifurcation interventions, in which OCT allowed optimization of the final procedural result, by detecting a dissection, intracoronary thrombus and by confirming complete ostial coverage by a stent. PMID- 22294548 TI - Investigating the effectiveness of St John's wort herb as an antimicrobial agent against mycobacteria. AB - A persistent need exists for effective treatment agents for mycobacterial infections. This research investigated the effectiveness of the Hypericum perforatum herb (commonly known as St John's wort; SJW) in its growth inhibition of mycobacteria. A SJW extract was effective at inhibiting five nonpathogenic Mycobacterium isolates and Bacillus subtilis, but not Escherichia coli. Quantitative studies of concentration sensitivity to the SJW extract were performed with minimal bactericidal concentrations (MBC) ranging from 0.33 to 2.66 mg extract/mL. The SJW compounds hyperforin (Hfn), hypericin (Hpn), and pseudohypericin (Phn) were quantified in the extract using HPLC. The SJW extract solution of 133 mg extract/mL used in this study contained 2.3 mg Hfn/mL, 0.8 mg Hpn/mL, and 2.1 mg Phn/mL. Purified Hfn, Hpn, and Phn were tested for inhibitory activity against Mycobacterium JLS (M. JLS) at similar concentrations used in the crude extract. While Hfn was inhibitory at 46 ug/mL, none of the purified SJW constituents were bactericidal at concentrations corresponding to SJW treatments. Scanning electron microscopy (SEM) analysis of SJW-treated M. JLS cells showed changes in cell surface morphology. PMID- 22294550 TI - Performance of interferon-gamma release assays in patients with inflammatory bowel disease: a systematic review and meta-analysis. AB - BACKGROUND: Guidelines mandate screening for latent tuberculosis infection (LTBI) prior to anti-tumor necrosis factor (anti-TNF) therapy in patients with inflammatory bowel disease (IBD). However, many are already on immunosuppressive therapy (IST) that may affect the precision of the Tuberculin skin test (TST). Our aim was to assess the performance of the new interferon-gamma release assays (IGRAs) to detect LTBI in patients with IBD. METHODS: MEDLINE and EMBASE were searched (up to June 2011) to identify studies evaluating the performance of IGRAs (QuantiFERON-TB Gold [QFT-2G], QuantiFERON-TB Gold In-Tube [QFT-3G] and T SPOT.TB) in individuals with IBD. Forest plots and pooled estimates using random effects models were created where applicable. RESULTS: Nine unique studies encompassing 1309 patients with IBD were included for analysis. The pooled concordance between the TST and QFT-2G/QFT-3G was 85% (95% confidence interval [CI] 77%-90%). The concordance of the TST and TSPOT.TB was 72% (95% CI 64%-78%). Studies assessing agreement reported more IGRA-/TST+ results versus IGRA+/TST- results. The pooled percentage of indeterminate results was 5% (95% CI 2%-9%) for QFT-2G/QFT-3G. TSPOT.TB showed similar results. Both positive QFT-2G/QFT-3G results (pooled odds ratio [OR] 0.37, 95% CI 0.16-0.87) and positive TST results (pooled OR 0.28, 95% CI 0.10-0.80) were significantly influenced by IST (both P = 0.02). CONCLUSIONS: While it remains difficult to determine superiority between the IGRAs and the TST, both are negatively affected by IST. Therefore, screening prior to initiation of IST should be considered. Nevertheless, it is imperative that all patients receive screening prior to anti-TNF therapy. PMID- 22294551 TI - N-Acetylglucosaminyltransferase V regulates TGF-beta response in hepatic stellate cells and the progression of steatohepatitis. AB - N-Acetylglucosaminyltransferase V (GnT-V), catalyzing beta1-6 branching in asparagine-linked oligosaccharides, is one of the most important glycosyltransferases involved in tumor metastasis and carcinogenesis. Although the expression of GnT-V is induced in chronic liver diseases, the biological meaning of GnT-V in the diseases remains unknown. The aim of this study was to investigate the effects of GnT-V on the progression of chronic hepatitis, using GnT-V transgenic (Tg) mice fed a high fat and high cholesterol (HFHC) diet, an experimental model of murine steatohepatitis. Although enhanced hepatic lymphocytes infiltration and fibrosis were observed in wild-type (WT) mice fed the HFHC diet, they were dramatically prevented in Tg mice. In addition, the gene expression of inflammatory Th1 cytokines in the liver was significantly decreased in Tg mice than WT mice. Inhibition of liver fibrosis was due to the dysfunction of hepatic stellate cells (HSCs), which play pivotal roles in liver fibrosis through the production of transforming growth factor (TGF)-beta1. Although TGF beta1 signaling was enhanced in Tg mouse-derived HSCs (Tg-HSCs) compared with WT mouse-derived HSCs (WT-HSCs), collagen expression was significantly reduced in Tg HSCs. As a result from DNA microarray, cyclooxygenase-2 (COX2) expression, known as a negative feedback signal for TGF-beta1, was significantly elevated in Tg HSCs compared with WT-HSCs. Prostaglandin E2 (PGE2), the product of COX2, production was also significantly elevated in Tg-HSCs. COX2 inhibition by celecoxib decreased PGE2 and increased collagen expression in Tg-HSCs. In conclusion, GnT-V prevented steatohepatitis progression through modulating lymphocyte and HSC functions. PMID- 22294552 TI - Tumor suppressive microRNA-1285 regulates novel molecular targets: aberrant expression and functional significance in renal cell carcinoma. AB - MicroRNAs (miRNA) are non-coding RNAs, approximately 22 nucleotides in length, which function as post-transcriptional regulators. A large body of evidence indicates that miRNAs regulate the expression of cancer-related genes involved in proliferation, migration, invasion, and metastasis. The aim of this study was to identify novel cancer networks in renal cell carcinoma (RCC) based on miRNA expression signatures obtained from RCC clinical specimens. Expression signatures revealed that 103 miRNAs were significantly downregulated (more than 0.5-fold change) in RCC specimens. Functional screening (cell proliferation assays) was performed to identify tumor suppressive activities of 20 downregulated miRNAs. Restoration of mature miRNAs in cancer cells showed that 14 miRNAs (miR-1285, miR 206, miR-1, miR-135a, miR-429, miR-200c, miR-1291, miR-133b, miR-508-3p, miR-360 3p, miR-509-5p, miR-218, miR-335, miR-1255b and miR-1285) markedly inhibited cancer cell proliferation, suggesting that these miRNAs were candidate tumor suppressive miRNAs in RCC. We focused on miR-1285 because it significantly inhibited cancer cell proliferation, invasion, and migration following its transfection. We addressed miR-1285-regulated cancer networks by using genome wide gene expression analysis and bioinformatics. The data showed that transglutaminase 2 (TGM2) was directly regulated by miR-1285. Silencing of the target gene demonstrated significant inhibition of cell proliferation and invasion in the RCC cells. Furthermore, immunohistochemistry showed that TGM2 expression levels in RCC specimens were significantly higher than those in normal renal tissues. Downregulation of tumor suppressive miR-1285, which targets oncogenic genes including TGM2, might contribute to RCC development. Thus, miR 1285 modulates a novel molecular target and provides new insights into potential mechanisms of RCC oncogenesis. PMID- 22294553 TI - Hedgehog-EGFR cooperation response genes determine the oncogenic phenotype of basal cell carcinoma and tumour-initiating pancreatic cancer cells. AB - Inhibition of Hedgehog (HH)/GLI signalling in cancer is a promising therapeutic approach. Interactions between HH/GLI and other oncogenic pathways affect the strength and tumourigenicity of HH/GLI. Cooperation of HH/GLI with epidermal growth factor receptor (EGFR) signalling promotes transformation and cancer cell proliferation in vitro. However, the in vivo relevance of HH-EGFR signal integration and the critical downstream mediators are largely undefined. In this report we show that genetic and pharmacologic inhibition of EGFR signalling reduces tumour growth in mouse models of HH/GLI driven basal cell carcinoma (BCC). We describe HH-EGFR cooperation response genes including SOX2, SOX9, JUN, CXCR4 and FGF19 that are synergistically activated by HH-EGFR signal integration and required for in vivo growth of BCC cells and tumour-initiating pancreatic cancer cells. The data validate EGFR signalling as drug target in HH/GLI driven cancers and shed light on the molecular processes controlled by HH-EGFR signal cooperation, providing new therapeutic strategies based on combined targeting of HH-EGFR signalling and selected downstream target genes. PMID- 22294554 TI - Doubling the infliximab dose versus halving the infusion intervals in Crohn's disease patients with loss of response. AB - BACKGROUND: Intensifying infliximab therapy is often practiced in Crohn's disease (CD) patients losing response to the drug but there are no data if halving the interval is superior to doubling the dose. We aimed to assess the efficacy of infliximab dose intensification by interval-halving compared with dose-doubling. METHODS: A multicenter retrospective study of CD patients losing response to infliximab was undertaken. The clinical outcome of patients whose infusion intervals were halved (5 mg/kg/4 weeks) was compared with patients treated by dose-doubling (10 mg/kg/8 weeks). RESULTS: In all, 168 patients were included from 18 centers in Europe, USA, and Israel. Of these, 112 were intensified by dose-doubling and 56 received interval-halving strategy. Early response to dose escalation was experienced by 86/112 (77%) patients in the dose-doubling group compared with 37/56 patients (66%) in the interval-halving group (odds ratio [OR] 1.7, 95% confidence interval [CI] 0.8-3.4, P = 0.14). Sustained clinical response at 12 months postescalation was maintained in 50% of patients in the dose doubling group compared with 39% in the interval-halving group (OR 1.5, 95% CI 0.8-2.9, P = 0.2). On multivariate analysis, predictors of long-term response to escalation were a nonsmoking status, CD diagnosis between 16-40 years of age, and normal C-reactive protein (CRP). CONCLUSIONS: Dose intensification leads to a sustained regained response in 47% of CD patients who lost response to standard infliximab dose, but halving the infusion intervals is probably not superior to dose-doubling. Given the costs and patient inconvenience incurred by an additional infusion visit, the dose-doubling strategy may be preferable to the interval-halving strategy. PMID- 22294555 TI - Combined adverse effects of maternal smoking and high body mass index on heart development in offspring: evidence for interaction? AB - OBJECTIVE: To study the influence of a possible interaction between maternal smoking and high body mass index (BMI) on the occurrence of specific congenital heart anomalies (CHA) in offspring. DESIGN: Case-control study. SETTING: Data from a population-based birth defects registry in the Netherlands. PATIENTS: Cases were 797 children and fetuses born between 1997 and 2008 with isolated non syndromic CHA. They were classified into five cardiac subgroups: septal defects (n=349), right ventricular outflow tract obstructive anomalies (n=126), left ventricular outflow tract obstructive anomalies (n=139), conotruncal defects (n=115) and other CHA (n=68). Controls were 322 children and fetuses with chromosomal anomalies without cardiac anomalies. MAIN OUTCOME MEASURES: Investigation of whether an interaction between maternal smoking and high BMI influences the occurrence of CHA in offspring by calculation of the synergy factors and 95% CIs. RESULTS: As opposed to smoking or high BMI alone, the risk for CHA in the offspring of women with high BMI (>=25 kg/m(2)) who also smoked was significantly increased. The adjusted OR was 2.65 (95% CI 1.20 to 5.87) for all CHA, 2.60 (95% CI 1.05 to 6.47) for septal defects and 3.58 (95% CI 1.46 to 8.79) for outflow tract anomalies. The interaction between maternal high BMI and smoking contributed significantly to the occurrence of all offspring-CHA combined, and to the occurrence of all cardiac subgroup anomalies except right ventricular outflow tract obstructive anomalies. CONCLUSIONS: Maternal overweight and smoking may have a synergistic adverse effect on the development of the fetal heart. Overweight women who wish to become pregnant should be strongly encouraged to stop smoking and to lose weight. PMID- 22294556 TI - The safety of embryonic stem cell therapy relies on teratoma removal. PMID- 22294557 TI - Australian perspectives on surrogacy: the influence of cognitions, psychological and demographic characteristics. AB - BACKGROUND: The aim of the present study was to explore current Australian support levels for surrogacy treatments and also whether this support differed between traditional surrogacy and gestational surrogacy. The focus was also on understanding the underlying influences on surrogacy attitudes. It was hypothesized that cognitions, psychological and demographic characteristics would all predict attitudes to surrogacy and that cognitive concerns about surrogacy would be the strongest predictor. METHODS: Participants (N = 195: 79 male, 116 female; age range 18-76 years) were first-year psychology undergraduates (47%) and friends and associates of the authors (53%). They completed a survey pack which assessed attitudes and knowledge about surrogacy, as well as empathy and other personality characteristics. RESULTS: The results indicated that there has been a marked increase in support for surrogacy treatment in recent years, with nearly 80% of participants supporting surrogacy, and that support for gestational surrogacy was greater than that for traditional surrogacy (P< 0.001). As anticipated, cognitive concerns about surrogacy were the strongest predictors of surrogacy attitudes (R(2)= 0.393). CONCLUSIONS: A limitation of the present study was the use of a non-representative, self-selected sample that tended to be well educated and perhaps liberal minded. Despite this, given the high levels of support, it could be concluded that the recent, more permissive legislative changes, which were finalized in 2010, are reflective of the values of Australian society. PMID- 22294558 TI - Cost-of-illness studies and cost-effectiveness analyses in eating disorders: a systematic review. AB - OBJECTIVE: To review cost-of-illness studies (COIs) and cost-effectiveness analyses (CEAs) of eating disorders (EDs) and to describe their methodological quality. METHOD: A systematic literature search was done. Search results passed through a selection process, included studies were classified as COIs, CEAs, or "other cost studies" (OCS). Costs were inflated and converted to 2008 US$ purchasing power parities (PPP). Quality criteria were developed and applied to each study. RESULTS: Five COI, two CEA, and eleven "OCS" were reviewed. Most studies focused on anorexia nervosa and bulimia nervosa. Annual costs per patient ranged from 1,288 to 8,042 US$-PPP. All interventions, investigated in CEA, were more effective and less costly than the alternative treatments. DISCUSSION: The number of publications investigating costs in EDs has increased recently. However, no COI provided a comprehensive estimate of costs, and the comparability of CEA was limited. Nonetheless, the results indicate that the costs arising from EDs are substantial. PMID- 22294559 TI - Heart team discussion in managing patients with coronary artery disease: outcome and reproducibility. AB - Recent ESC/EACTS revascularization guidelines advocate a 'Heart Team' (HT) approach in the decision-making process when managing patients with coronary disease. We prospectively assessed HT decision-making in 150 patients analysing personnel attendance, data presented, the 'actioning' of the HT decision and, if not completed, then the reasons why. Additionally, 50 patients were specifically re-discussed after 1 year in order to assess consistency in decision-making. We have two HT meetings each week. At least one surgeon, interventional cardiologist and non-interventional cardiologist were present at all meetings. Data presented included patient demographics, symptoms, co-morbidities, coronary angiography, left ventricular function and other relevant investigations, e.g. echocardiograms. HT decisions included continued medical treatment (22%), percutaneous coronary intervention (PCI; 22%), coronary-artery bypass grafting (CABG; 34%) or further investigations such as pressure wire studies, dobutamine stress echo or cardiac magnetic resonance imaging (22%). These decisions were fully undertaken in 86% of patients. Reasons for aberration in the remaining 21 patients included patient refusal (CABG 29%, PCI 10%) and further co-morbidities (28%). On re-discussion of the same patient data (n = 50) a year later, 24% of decisions differed from the original HT recommendations reflecting the fact that, for certain coronary artery disease pattern, either CABG or PCI could be appropriate. PMID- 22294560 TI - Outcome after redo-mitral valve replacement in adult patients: a 10-year single centre experience. AB - The aim of this study was to investigate the overall outcome of adult patients undergoing redo-mitral valve replacement (redo-MVR) at our institution. Forty nine patients (24 males) underwent redo-MVR with either bioprosthetic (n = 24) or mechanical valves (n = 25) between January 2000 and 2010. Median age of patients was 63 years (range 21-80 years), and the mean additive EuroSCORE was 12 +/- 4. Median time to re-operation was 8.2 +/- 6.6 years for first time redo-MVR and 6.4 +/- 5.6 years for second-time redo-MVR. Indications included prosthetic endocarditis (n = 22), para-prosthetic leak (n = 12), structural valve degeneration (n = 8), prosthetic valve thrombosis (n = 6) and malignancy (n = 1). The mean follow-up was 47.5 +/- 37.0 months (range 0.1-112.3 months). In-hospital mortality was 12% (n = 6). Mean hospital stay was 17 +/- 11 days (range 8-50 days). Actuarial survival at 1 and 5 years was 81 +/- 5% and 72 +/- 6%, respectively. Three patients required re-intervention: two for prosthetic valve endocarditis and one for para-prosthetic leak. Multivariate analysis showed that overall survival was associated with the LVEF < 50% (P < 0.001), concomitant AVR (P < 0.001) and urgent surgery (P = 0.03). PMID- 22294561 TI - Abstracts from the American Society for Apheresis 33rd Annual Meeting, April 11 14, 2012, Atlanta, Georgia. PMID- 22294562 TI - A computational model of bleb formation. AB - Blebbing occurs when the cytoskeleton detaches from the cell membrane, resulting in the pressure-driven flow of cytosol towards the area of detachment and the local expansion of the cell membrane. Recent interest has focused on cells that use blebbing for migrating through 3D fibrous matrices. In particular, metastatic cancer cells have been shown to use blebs for motility. A dynamic computational model of the cell is presented that includes mechanics of and the interactions between the intracellular fluid, the actin cortex and the cell membrane. The computational model is used to explore the relative roles in bleb formation time of cytoplasmic viscosity and drag between the cortex and the cytosol. A regime of values for the drag coefficient and cytoplasmic viscosity values that match bleb formation timescales is presented. The model results are then used to predict the Darcy permeability and the volume fraction of the cortex. PMID- 22294563 TI - The 6-PACK programme to decrease falls and fall-related injuries in acute hospitals: protocol for an economic evaluation alongside a cluster randomised controlled trial. AB - BACKGROUND: Falls are a common hospital occurrence complicating the care of patients. From an economic perspective, the impact of in-hospital falls and related injuries is substantial. However, few studies have examined the economic implications of falls prevention interventions in an acute care setting. The 6 PACK programme is a targeted nurse delivered falls prevention programme designed specifically for acute hospital wards. It includes a risk assessment tool and six simple strategies that nurses apply to patients classified as high-risk by the tool. OBJECTIVE: To examine the incremental cost-effectiveness of the 6-PACK programme for the prevention of falls and fall-related injuries, compared with usual care practice, from an acute hospital perspective. METHODS AND DESIGN: The 6-PACK project is a multicentre cluster randomised controlled trial (RCT) that includes 24 acute medical and surgical wards from six hospitals in Australia to investigate the efficacy of the 6-PACK programme. This economic evaluation will be conducted alongside the 6-PACK cluster RCT. Outcome and hospitalisation cost data will be prospectively collected on approximately 16,000 patients admitted to the participating wards during the 12-month trial period. The results of the economic evaluation will be expressed as 'cost or saving per fall prevented' and 'cost or saving per fall-related injury prevented' calculated from differences in mean costs and effects in the intervention and control groups, to generate an incremental cost-effectiveness ratio (ICER). DISCUSSION: This economic evaluation will provide an opportunity to explore the cost-effectiveness of a targeted nurse delivered falls prevention programme for reducing in-hospital falls and fall related injuries. This protocol provides a detailed statement of a planned economic evaluation conducted alongside a cluster RCT to investigate the efficacy of the 6-PACK programme to prevent falls and fall-related injuries. TRIAL REGISTRATION NUMBER: The protocol for the cluster RCT is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12611000332921). PMID- 22294564 TI - A consideration of severity is sufficient to focus our prevention efforts. PMID- 22294566 TI - Photo quiz. Rash in a patient with ovarian cancer. PMID- 22294575 TI - Introduction to workshop: adventitious viruses in biologics--detection and mitigation strategies. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294576 TI - Evolution of approaches to viral safety issues for biological products. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) Approaches to viral safety issues for biological products have evolved during the past 50+ years. The first cell culture products (viral vaccines) relied largely on the use of in vitro and in vivo virus screening assays that were based upon infectivity of adventitious viral agents. The use of Cohn fractionation and pasteurization by manufacturers of plasma derivatives introduced the concepts that purification and treatment with physical and chemical agents could greatly reduce the risk of viral contamination of human albumin and immunoglobulin products. But the limitations of such approaches became clear for thermolabile products that were removed early in fractionation such as antihemophilic factors, which transmitted hepatitis viruses and HIV-1 to some product recipients. These successes and limitations were taken into account by the early developers of recombinant DNA (rDNA)-derived cell culture products and by regulatory agencies, leading to the utilization of cloning technology to reduce/eliminate contamination due to human viruses and purification technologies to physically remove and inactivate adventitious and endogenous viruses, along with cell banking and cell bank characterization for adventitious and endogenous viruses, viral screening of biological raw materials, and testing of cell culture harvests, to ensure virus safety. Later development and incorporation of nanofiltration technology in the manufacturing process provided additional assurance of viral clearance for safety of biotechnology products. These measures have proven very effective at preventing iatrogenic infection of recipients of biotechnology products; however, viral contamination of production cell cultures has occasionally occurred. Screening tests for viral contamination in raw materials have not proven practical by themselves to prevent contamination of cell cultures, but they can be made more effective by coupling with treatment using physical or chemical agents to further reduce the hypothetical viral loads present in cell culture raw materials. Recent advances in polymerase chain reaction (PCR) technology have allowed preharvest testing for specific viral agents to reduce the risk of cell culture contamination by specific viruses in the harvest material. Examples of each of these stages in the evolution of virus detection methods are described and assessed in this paper. PMID- 22294577 TI - Regulatory approaches for control of viral contamination of vaccines. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) Improved assurance that vaccines do not contain harmful adventitious agents is expected to enhance public confidence and promote vaccine benefit. The recent discovery of porcine circovirus 1 in some rotavirus vaccines using massively parallel sequencing suggests that newer technologies could be employed both to identify potential adventitious viral agents and to provide increased assurance that such agents are absent. This article includes a discussion of the new virus detection methods and approaches that could be used to facilitate their use in a regulatory setting. PMID- 22294578 TI - Risk mitigation strategies for viral contamination of biotechnology products: consideration of best practices. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) Viral contamination of biotech product facilities is a potentially devastating manufacturing risk and, unfortunately, is more common than is generally reported or previously appreciated. Although viral contaminants of biotech products are thought to originate principally from biological raw materials, all potential process risks merit evaluation. Limitations to existing methods for virus detection are becoming evident as emerging viruses have contaminated facilities and disrupted supplies of critical products. New technologies, such as broad-based polymerase chain reaction screens for multiple virus types, are increasingly becoming available to detect adventitious viral contamination and thus, mitigate risks to biotech products and processes. Further, the industry embrace of quality risk management that promotes improvements in testing stratagems, enhanced viral inactivation methods for raw materials, implementation and standardization of robust viral clearance procedures, and efforts to learn from both epidemiologic screening of raw material sources and from the experience of other manufacturers with regard to this problem will serve to enhance the safety of biotech products available to patients. Based on this evolving landscape, we propose a set of principles for manufacturers of biotech products: Pillars of Risk Mitigation for Viral Contamination of Biotech Products. PMID- 22294579 TI - Current European regulations for control of adventitious virus safety. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294580 TI - Mouse Minute Virus (MMV) Contamination--A Case Study: Detection, Root Cause Determination, and Corrective Actions. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) The production of biologic drugs using mammalian cell production systems offers the benefits of high yield, proper protein folding, and faithful post-translational modifications. However, mammalian cell culture is vulnerable to contamination with adventitious agents, including mouse minute virus (MMV). The case study presented here demonstrates that MMV is a ubiquitous threat to CHO (Chinese hamster ovary) cell-based production of biologic drugs and that animal-free media components can be a contamination source. Compounding the risk posed by MMV, the contamination may be "silent," with no impact on cell viability and product titers. Furthermore, contamination may not be detected using in vitro virus assays, and assays based on PCR (polymerase chain reaction) are required for reliable detection. The development of effective corrective and preventative action (CAPA) was greatly aided by the identification of the source of the contamination as an animal-free recombinant media additive. The execution of a CAPA that included disposal of contaminated materials, decontamination of the facility, and replacement of the contaminated raw material allowed the resumption of MMV-free production. PMID- 22294581 TI - Adventitious Agent Risk Assessment Case Study: Evaluation of RotaTeq(R) for the Presence of Porcine Circovirus. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) In June of 2010, results of metagenomic and panmicrobial microarray analysis of a number of commercially available vaccine products were published, identifying the unexpected presence of porcine circovirus (PCV) in of one of the vaccine products tested. This testing did not detect any sequences of contaminating viruses in RotaTeq(r) (rotavirus vaccine, live, oral, pentavalent, RV5, Merck & Co., Inc., Whitehouse Station, NJ). To confirm this finding, Merck developed and applied a number of polymerase chain reaction-based analytical methods and a test algorithm to systematically demonstrate the absence of infectious PCV in RotaTeq(r). This paper will describe the methodology and rationale developed to thoroughly assess key starting materials, product intermediates, and final product to demonstrate the absence of infectious PCV, and the continued quality of this product. This approach could be applied to assess the validity of other adventitious agent risks encountered in biological processes and products. PMID- 22294582 TI - A biotech production facility contamination case study--minute mouse virus. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294583 TI - Case study of apparent virus contamination in biopharmaceutical product at centocor. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294584 TI - Contamination by porcine circovirus type 1: findings, investigations, and learnings. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294585 TI - Identification and remediation of a cell culture virus contamination. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294586 TI - Summary of breakout session e. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294587 TI - Chlorine dioxide remediation of a virus-contaminated manufacturing facility. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) Chlorine dioxide fumigation was successfully used to decontaminate a virally contaminated biotech manufacturing facility. Addressing safety, product quality, and corrosion risks were important factors in planning the building fumigation. Studies were performed to define the conditions in which minute mouse virus (MMV) is inactivated by chlorine dioxide and to understand equipment and facility risks. Written plans and procedures documented activities necessary to safely fumigate the building and requalify it to manufacture commercial product. PMID- 22294588 TI - Summary of breakout session f: facility and equipment decontamination strategies. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294589 TI - Current testing methods and challenges for detection of adventitious viruses. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) Adventitious viruses are a major safety concern in biological products. This paper discusses various sources of virus contamination and approaches to develop a comprehensive detection and mitigation strategy for product safety. Additionally, general safety concerns related to adventitious agents in biologics and current testing recommendations by the Center for Biologics Evaluation and Research for demonstrating the absence of adventitious agents in viral vaccines will be presented. The limitations of the conventional assays and the need for and consideration of new technologies for broad detection of novel agents will also be discussed. PMID- 22294590 TI - Theory and practice of conventional adventitious virus testing. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) For decades conventional tests in cell cultures and in laboratory animals have served as standard methods for broad-spectrum screening for adventitious viruses. New virus detection methods based on molecular biology have broadened and improved our knowledge about potential contaminating viruses and about the suitability of the conventional test methods. This paper summarizes and discusses practical aspects of conventional test schemes, such as detectability of various viruses, questionable or false-positive results, animal numbers needed, time and cost of testing, and applicability for rapidly changing starting materials. Strategies to improve the virus safety of biological medicinal products are proposed. The strategies should be based upon a flexible application of existing and new methods along with a scientifically based risk assessment. However, testing alone does not guarantee the absence of adventitious agents and must be accompanied by virus removing or virus inactivating process steps for critical starting materials, raw materials, and for the drug product. PMID- 22294591 TI - Broadening our expectations for viral safety risk mitigation. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) The production of biotechnology products using mammalian cell lines offers an inherent risk of viral contamination because of the scale of the process and the complexity of the materials employed. The testing of production cell lines, raw materials, and test execution at appropriate stages of production all combined with viral inactivation or removal strategies ensures that an infectious agent is absent from the purified final product. Perhaps because of these efforts, biotechnology products have not been linked to a negative clinical consequence. However, manufacturing viral contaminations still do occur and may have a great potential negative impact to our patients by disrupting the drug product supply chain. In this paper, additional end-to-end complementary viral safety program considerations are suggested beyond the traditional viral testing and inactivation/removal strategies. These additional points of consideration should be thought of as augmenting the above approaches to further provide a reasonable measure of mitigating the risk of viral contaminations within the biopharmaceutical manufacturing facility. The scope of this paper is on biologics produced in mammalian cells with an emphasis on viral contaminations involving Chinese hamster ovary cell production, although for the examples given as lessons learned with previous industry contaminations, vaccine production issues have been included as a general reference. PMID- 22294592 TI - Overview of emerging technologies to detect adventitious agents. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294593 TI - Breakout session C summary: current virus detection methods. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294594 TI - Massively parallel sequencing for the detection of adventitious viruses. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) The rate at which unknown adventitious agents are being discovered is accelerating. The ability to mitigate this risk begins with detection. Several molecular technologies for the detection of adventitious agent genomic signatures are reviewed here. Massively parallel sequencing (MP-Seq) is distinguished by its breadth of coverage. Supported by trained virologists and as part of a quality system, MP-Seq can be an early detection method for safe production of biologics. PMID- 22294595 TI - Detection of adventitious viruses from biologicals using a broad-spectrum microbial detection array. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) We designed the Lawrence Livermore Microbial Detection Array (LLMDA), which contains 388,000 DNA probes. This array can detect any sequenced viruses or bacteria within 24 h. In addition, the oligonucleotide probes were selected to enable detection of novel, divergent species with homology to sequenced organisms. We recently used this array to identify an adventitious virus from a vaccine product. We have also used this array to detect viral and bacterial infections from various human clinical samples. Broad-spectrum microbial detection microarrays are efficient and cost effective tools to rapidly screen cell bank samples, raw materials, vaccine samples, and clinical samples to ensure drug, food, and health safety in the United States and worldwide. PMID- 22294596 TI - Evaluation of a single-platform, rapid, nucleic Acid-based technology for detection of adventitious contaminants of cell culture. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294597 TI - Use of DOP-PCR in Non-Specific Virus Detection. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294598 TI - Detection of Latent Retroviruses in Vaccine-related Cell Substrates: Investigation of RT Activity Produced by Chemical Induction of Vero Cells. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) The detection of known and novel viruses is important for cell substrate and vaccine safety. A major challenge is detection of latent viruses such as endogenous retroviruses and oncogenic DNA viruses. We have evaluated activation of endogenous retroviruses in a Vero cell line using chemical induction and various conventional and emerging methods for virus detection and characterization. In addition, infectivity studies were done to determine whether any induced virus particles were replication competent. This approach may be used for enhancing vaccine safety by assessing the presence of potential chemically-inducible, latent viruses in cell substrates to be used for vaccine manufacture. PMID- 22294599 TI - Advanced Techniques for Detection and Identification of Viral Contaminants Using the Ibis PLEX-ID Universal Biosensor. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294600 TI - A microarray platform for virus detection and identification. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294601 TI - Nanostring's nCounter--A True Digital Target Profiling Technology. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294602 TI - PDA Cell Substrate Task Force: Emerging Technologies for Virus Detection Technical Document--A Progress Report. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294603 TI - Adventitious Agents: Issues and Considerations during Pre-Approval Reviews and Inspections. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) There are potential risks for adventitious agent contamination at every stage in the lifecycle of a product. This can range from an impact on product quality that must be investigated and corrected to the temporary shutdown of manufacturing altogether. An assessment of the risk management plans and the associated testing and proper manufacturing controls will be part of the review and inspection at the pre approval stage in the product lifecycle, and the effectiveness of the mitigating activities will be monitored as part of the activities as well. Appropriate measures aiming at preventing or reducing adventitious agents should be considered as part of the overall plan to ensure both product quality and continued manufacturing. PMID- 22294604 TI - FDA post-approval expectations for adventitious virus contamination prevention. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294605 TI - Summary of Breakout Session B: Regulatory Expectations for CGMP. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294606 TI - Practicing safe cell culture: applied process designs for minimizing virus contamination risk. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) Genentech responded to a virus contamination in its biologics manufacturing facility by developing and implementing a series of barriers specifically designed to prevent recurrence of this significant and impactful event. The barriers included steps to inactivate or remove potential virus particles from the many raw materials used in cell culture processing. Additionally, analytical testing barriers provided protection of the downstream processing areas should a culture contamination occur, and robust virus clearance capability provided further assurance of virus safety should a low level contamination go undetected. This conference proceeding will review Genentech's approach, and lessons learned, in minimizing virus contamination risk in cell culture processes through multiple layers of targeted barriers designed to deliver biologics products with high success rates. PMID- 22294607 TI - Application of Risk Assessments in the Design of the Overall Viral Control Strategy Used during the Manufacture and Testing of Live Virus Vaccines. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) It is important to include a risk assessment process in the overall viral control strategy used during the manufacture and testing of live virus vaccines. Because the product is itself a virus, traditional viral clearance steps are generally not included in the manufacturing process, and there is normally no inactivation step in the manufacturing process either. The risk assessment is therefore necessary to identify potential sources for entry of adventitious agents into the vaccine, and to develop a strategy to minimize or eliminate the sources through which adventitious agents can enter the vaccine. The risk assessment can also be used to tailor the biosafety testing that is performed on raw materials, vaccine seeds, vaccine bulk materials, and final product. Biosafety testing is normally designed to ensure the detection of both known and unknown adventitious agents, but the results of the risk assessment can be used to put in place a biosafety testing strategy designed to maximize the detection of an adventitious agent that is potentially likely to be present in the vaccine. The risk assessment therefore enables the development of a comprehensive viral control strategy and provides a higher level of assurance that the vaccine will be free from contamination by adventitious agents. PMID- 22294608 TI - Viral Safety of Plasma-derived Products. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294609 TI - Application of quality by design in the control of adventitious viruses: gaps in current processes in the prevention of virus contaminants. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294610 TI - Breakout Session A: Elimination or Treatment of High-risk Raw Materials. AB - CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). PMID- 22294611 TI - A fresh start--but business as usual. PMID- 22294612 TI - MicroRNAs and their roles in aging. AB - MicroRNAs (miRNAs) are a class of short non-coding RNAs that bind mRNAs through partial base-pair complementarity with their target genes, resulting in post transcriptional repression of gene expression. The role of miRNAs in controlling aging processes has been uncovered recently with the discovery of miRNAs that regulate lifespan in the nematode Caenorhabditis elegans through insulin and insulin-like growth factor-1 signaling and DNA damage checkpoint factors. Furthermore, numerous miRNAs are differentially expressed during aging in C. elegans, but the specific functions of many of these miRNAs are still unknown. Recently, various miRNAs have been identified that are up- or down-regulated during mammalian aging by comparing their tissue-specific expression in younger and older mice. In addition, many miRNAs have been implicated in governing senescence in a variety of human cell lines, and the precise functions of some of these miRNAs in regulating cellular senescence have helped to elucidate mechanisms underlying aging. In this Commentary, we review the various regulatory roles of miRNAs during aging processes. We highlight how certain miRNAs can regulate aging on the level of organism lifespan, tissue aging or cellular senescence. Finally, we discuss future approaches that might be used to investigate the mechanisms by which miRNAs govern aging processes. PMID- 22294613 TI - The role of clathrin in mitotic spindle organisation. AB - Clathrin, a protein best known for its role in membrane trafficking, has been recognised for many years as localising to the spindle apparatus during mitosis, but its function at the spindle remained unclear. Recent work has better defined the role of clathrin in the function of the mitotic spindle and proposed that clathrin crosslinks the microtubules (MTs) comprising the kinetochore fibres (K fibres) in the mitotic spindle. This mitotic function is unrelated to the role of clathrin in membrane trafficking and occurs in partnership with two other spindle proteins: transforming acidic coiled-coil protein 3 (TACC3) and colonic hepatic tumour overexpressed gene (ch-TOG; also known as cytoskeleton-associated protein 5, CKAP5). This review summarises the role of clathrin in mitotic spindle organisation with an emphasis on the recent discovery of the TACC3-ch-TOG clathrin complex. PMID- 22294614 TI - Drug-refractory ventricular tachycardias after myocarditis: endocardial and epicardial radiofrequency catheter ablation. AB - BACKGROUND: Ventricular tachycardia (VT) is a significant therapeutic challenge in patients with myocarditis. This study aimed to assess the efficacy and safety of radiofrequency catheter ablation (RFCA) of VT in patients with myocarditis. METHODS AND RESULTS: We enrolled 20 patients (15 men; age, 42 [28-52] years) with a history of biopsy-proven viral myocarditis and drug-refractory VT; 5 patients presented with electrical storm. The median left ventricular ejection fraction was 55% (45-60%). All patients underwent endocardial RFCA with an irrigated catheter, using contact electroanatomic mapping. Recurrence of sustained VT after endocardial RFCA was treated with additional epicardial RFCA. Endocardial RFCA was acutely successful in 14 patients (70%) while in the remaining 6 (30%) clinical VT was successfully ablated by epicardial RFCA. In 1 patient, hemodynamic instability required an intra-aortic balloon pump to complete RFCA. No major complication occurred during or after RFCA. Over a median follow-up time of 28 (11-48) months, 18 patients (90%) remained free of sustained VT; 2 patients (10%, both with baseline left ventricular ejection fraction<=35%) died of acute heart failure unrelated to ventricular arrhythmias. CONCLUSIONS: In patients with myocarditis, RFCA of drug-refractory VT is feasible, safe, and effective. Epicardial RFCA should be considered as an important therapeutic option to increase success rate. PMID- 22294615 TI - Left atrial wall stress distribution and its relationship to electrophysiologic remodeling in persistent atrial fibrillation. AB - BACKGROUND: Atrial stretch causes remodeling that predisposes to atrial fibrillation. We tested the hypothesis that peaks in left atrial (LA) wall stress are associated with focal remodeling. METHODS AND RESULTS: Nineteen patients underwent LA mapping before catheter ablation for persistent atrial fibrillation. Finite Element Analysis was used to predict wall stress distribution based on LA geometry from CT. The relationship was assessed between wall stress and (1) electrogram voltage and (2) complex fractionated atrial electrograms (CFAE), using CFAE mean (the mean interval between deflections). Wall stress varied widely within atria and between subjects (median, 36 kPa; interquartile range, 26 51 kP). Peaks in wall stress (>=90th percentile) were common at the pulmonary vein (PV) ostia (93%), the appendage ridge (100%), the high posterior wall (84%), and the anterior wall and septal regions (42-84%). Electrogram voltage showed an inverse relationship across quartiles for wall stress (19% difference across quartiles, P=0.016). There was no effect on CFAE mean across quartiles of wall stress. Receiver operating characteristic analysis showed high wall stress was associated with low voltage (ie, <0.5 mV) and electrical scar (ie, <0.05 mV; both P<0.0001) and with absence of CFAE (ie, CFAE mean <120 ms; P<0.0001). However, peaks in wall stress and CFAE were found at 88% of PV ostia. CONCLUSIONS: Peaks in wall stress were associated with areas of low voltage, suggestive of focal remodeling. Although peaks in wall stress were not associated with LA CFAE, the PV ostia may respond differently. PMID- 22294616 TI - Genetic analysis of atherosclerosis and glucose homeostasis in an intercross between C57BL/6 and BALB/cJ apolipoprotein E-deficient mice. AB - BACKGROUND: Diabetic patients have an increased risk of developing atherosclerosis and related complications compared with nondiabetic individuals. The increased cardiovascular risk associated with diabetes is due in part to genetic variations that influence both glucose homeostasis and atherosclerotic lesion growth. Mouse strains C57BL/6J (B6) and BALB/cJ (BALB) exhibit distinct differences in fasting plasma glucose and atherosclerotic lesion size when deficient in apolipoprotein E (Apoe(-/-)). Quantitative trait locus (QTL) analysis was performed to determine genetic factors influencing the 2 phenotypes. METHODS AND RESULTS: Female F(2) mice (n=266) were generated from an intercross between B6.Apoe(-/-) and BALB.Apoe(-/-) mice and fed a Western diet for 12 weeks. Atherosclerotic lesions in the aortic root, fasting plasma glucose, and body weight were measured. 130 microsatellite markers across the entire genome were genotyped. Four significant QTLs, Ath1 on chromosome (Chr) 1, Ath41 on Chr2, Ath42 on Chr5, and Ath29 on Chr9, and 1 suggestive QTL on Chr4, were identified for atherosclerotic lesion size. Four significant QTLs, Bglu3 and Bglu12 on Chr1, Bglu13 on Chr5, Bglu15 on Chr12, and 2 suggestive QTLs on Chr9 and Chr15 were identified for fasting glucose levels on the chow diet. Two significant QTLs, Bglu3 and Bglu13, and 1 suggestive locus on Chr8 were identified for fasting glucose on the Western diet. One significant locus on Chr1 and 2 suggestive loci on Chr9 and Chr19 were identified for body weight. Ath1 and Ath42 coincided with Bglu3 and Bglu13, respectively, in the confidence interval. CONCLUSIONS: We have identified novel QTLs that have major influences on atherosclerotic lesion size and glucose homeostasis. The colocalization of QTLs for atherosclerosis and diabetes suggests possible genetic connections between the 2 diseases. PMID- 22294617 TI - Loss of abaxial leaf epicuticular wax in Medicago truncatula irg1/palm1 mutants results in reduced spore differentiation of anthracnose and nonhost rust pathogens. AB - To identify genes that confer nonhost resistance to biotrophic fungal pathogens, we did a forward-genetics screen using Medicago truncatula Tnt1 retrotransposon insertion lines. From this screen, we identified an inhibitor of rust germ tube differentation1 (irg1) mutant that failed to promote preinfection structure differentiation of two rust pathogens, Phakopsora pachyrhizi and Puccinia emaculata, and one anthracnose pathogen, Colletotrichum trifolii, on the abaxial leaf surface. Cytological and chemical analyses revealed that the inhibition of rust preinfection structures in irg1 mutants is due to complete loss of the abaxial epicuticular wax crystals and reduced surface hydrophobicity. The composition of waxes on abaxial leaf surface of irg1 mutants had >90% reduction of C30 primary alcohols and a preferential increase of C29 and C31 alkanes compared with the wild type. IRG1 encodes a Cys(2)His(2) zinc finger transcription factor, PALM1, which also controls dissected leaf morphology in M. truncatula. Transcriptome analysis of irg1/palm1 mutants revealed downregulation of eceriferum4, an enzyme implicated in primary alcohol biosynthesis, and MYB96, a major transcription factor that regulates wax biosynthesis. Our results demonstrate that PALM1 plays a role in regulating epicuticular wax metabolism and transport and that epicuticular wax influences spore differentiation of host and nonhost fungal pathogens. PMID- 22294618 TI - The influence of light on microtubule dynamics and alignment in the Arabidopsis hypocotyl. AB - Light and dark have antagonistic effects on shoot elongation, but little is known about how these effects are translated into changes of shape. Here we provide genetic evidence that the light/gibberellin-signaling pathway affects the properties of microtubules required to reorient growth. To follow microtubule dynamics for hours without triggering photomorphogenic inhibition of growth, we used Arabidopsis thaliana light mutants in the gibberellic acid/DELLA pathway. Particle velocimetry was used to map the mass movement of microtubule plus ends, providing new insight into the way that microtubules switch between orthogonal axes upon the onset of growth. Longitudinal microtubules are known to signal growth cessation, but we observed that cells also self-organize a strikingly bipolarized longitudinal array before bursts of growth. This gives way to a radial microtubule star that, far from being a random array, seems to be a key transitional step to the transverse array, forecasting the faster elongation that follows. Computational modeling provides mechanistic insight into these transitions. In the faster-growing mutants, the microtubules were found to have faster polymerization rates and to undergo faster reorientations. This suggests a mechanism in which the light-signaling pathway modifies the dynamics of microtubules and their ability to switch between orthogonal axes. PMID- 22294619 TI - POM-POM2/cellulose synthase interacting1 is essential for the functional association of cellulose synthase and microtubules in Arabidopsis. AB - In plants, regulation of cellulose synthesis is fundamental for morphogenesis and plant growth. Cellulose is synthesized at the plasma membrane, and the orientation of synthesis is guided by cortical microtubules; however, the guiding mechanism is currently unknown. We show that the conditional root elongation pom2 mutants are impaired in cell elongation, fertility, and microtubule-related functions. Map-based cloning of the POM-POM2 locus revealed that it is allelic to CELLULOSE SYNTHASE INTERACTING1 (CSI1). Fluorescently tagged POM2/CSI1s associated with both plasma membrane-located cellulose synthases (CESAs) and post Golgi CESA-containing compartments. Interestingly, while CESA insertions coincided with cortical microtubules in the pom2/csi1 mutants, the microtubule defined movement of the CESAs was significantly reduced in the mutant. We propose that POM2/CSI1 provides a scaffold between the CESAs and cortical microtubules that guide cellulose synthesis. PMID- 22294620 TI - Regulation of the photorespiratory GLDPA gene in C(4) flaveria: an intricate interplay of transcriptional and posttranscriptional processes. AB - The mitochondrial Gly decarboxylase complex (GDC) is a key component of the photorespiratory pathway that occurs in all photosynthetically active tissues of C(3) plants but is restricted to bundle sheath cells in C(4) species. GDC is also required for general cellular C(1) metabolism. In the Asteracean C(4) species Flaveria trinervia, a single functional GLDP gene, GLDPA, encodes the P-subunit of GDC, a decarboxylating Gly dehydrogenase. GLDPA promoter reporter gene fusion studies revealed that this promoter is active in bundle sheath cells and the vasculature of transgenic Flaveria bidentis (C(4)) and the Brassicacean C(3) species Arabidopsis thaliana, suggesting the existence of an evolutionarily conserved gene regulatory system in the bundle sheath. Here, we demonstrate that GLDPA gene regulation is achieved by an intricate interplay of transcriptional and posttranscriptional mechanisms. The GLDPA promoter is composed of two tandem promoters, P(R2) and P(R7), that together ensure a strong bundle sheath expression. While the proximal promoter (P(R7)) is active in the bundle sheath and vasculature, the distal promoter (P(R2)) drives uniform expression in all leaf chlorenchyma cells and the vasculature. An intron in the 5' untranslated leader of P(R2)-derived transcripts is inefficiently spliced and apparently suppresses the output of P(R2) by eliciting RNA decay. PMID- 22294622 TI - Cytokine levels in human synovial fluid during the different stages of acute gout: role of transforming growth factor beta1 in the resolution phase. AB - OBJECTIVES: To determine the most relevant parameters in synovial fluid (SF) during the various stages of acute gout. METHODS: SFs from 38 gouty patients were analysed for white blood cell (WBC) count, percentage of polymorphonuclear cells (PMNs) and levels of interleukin 1beta (IL-1beta), IL-6, IL-8, tumour necrosis factoralpha (TNFalpha) and transforming growth factor beta1 (TGFbeta1). Patients were divided into three groups according to the length of time since onset of the attack: phase I (0-48 h), phase II (days 3-4) and phase III (days 5-7). RESULTS: Levels of WBCs were similar in SFs from phases I and II, while phase III showed the lowest WBC count. Percentages of PMNs were raised in all SFs. None of the cytokines analysed differed between phases I and II except for TGFbeta1, which was higher in phase II. IL-1beta, IL-6 and TNFalpha were higher in group 1 than in group 3. Levels of all the cytokines assessed, with the exception of TGFbeta1, were significantly lower in phase III than in phase II IL-1beta, p<0.05; IL-6, p<0.01; IL-8, p<0.001; TNFalpha, p<0.05).TGFbeta1 levels were highest in SFs from phase III. CONCLUSION: Cytokine levels in SFs may change depending on the different stages of acute gout, highlighting the role of TGFbeta1 in the resolution of gout. PMID- 22294621 TI - Rheb is a critical regulator of autophagy during myocardial ischemia: pathophysiological implications in obesity and metabolic syndrome. AB - BACKGROUND: Rheb is a GTP-binding protein that promotes cell survival and mediates the cellular response to energy deprivation (ED). The role of Rheb in the regulation of cell survival during ED has not been investigated in the heart. METHODS AND RESULTS: Rheb is inactivated during cardiomyocyte (CM) glucose deprivation (GD) in vitro, and during acute myocardial ischemia in vivo. Rheb inhibition causes mTORC1 inhibition, because forced activation of Rheb, through Rheb overexpression in vitro and through inducible cardiac-specific Rheb overexpression in vivo, restored mTORC1 activity. Restoration of mTORC1 activity reduced CM survival during GD and increased infarct size after ischemia, both of which were accompanied by inhibition of autophagy, whereas Rheb knockdown increased autophagy and CM survival. Rheb inhibits autophagy mostly through Atg7 depletion. Restoration of autophagy, through Atg7 reexpression and inhibition of mTORC1, increased cellular ATP content and reduced endoplasmic reticulum stress, thereby reducing CM death induced by Rheb activation. Mice with high-fat diet induced obesity and metabolic syndrome (HFD mice) exhibited deregulated cardiac activation of Rheb and mTORC1, particularly during ischemia. HFD mice presented inhibition of cardiac autophagy and displayed increased ischemic injury. Pharmacological and genetic inhibition of mTORC1 restored autophagy and abrogated the increase in infarct size observed in HFD mice, but they failed to protect HFD mice in the presence of genetic disruption of autophagy. CONCLUSIONS: Inactivation of Rheb protects CMs during ED through activation of autophagy. Rheb and mTORC1 may represent therapeutic targets to reduce myocardial damage during ischemia, particularly in obese patients. PMID- 22294623 TI - Association of UBE2L3 polymorphisms with diffuse cutaneous systemic sclerosis in a Japanese population. PMID- 22294624 TI - ASAS recommendations for variables to be collected in clinical trials/epidemiological studies of spondyloarthritis. PMID- 22294625 TI - A comparative effectiveness study of adalimumab, etanercept and infliximab in biologically naive and switched rheumatoid arthritis patients: results from the US CORRONA registry. AB - PURPOSE: To compare the effectiveness of anti-tumour necrosis factor (TNF) agents in biologically naive and 'switched' rheumatoid arthritis (RA) patients. METHODS: RA patients enrolled in the CORRONA registry newly prescribed adalimumab (n=874), etanercept (n=640), or infliximab (n=728) were stratified based on previous anti TNF use. Clinical effectiveness at 6, 12 and 24 months was examined using the modified American College of Rheumatology response criteria (mACR20/50/70) and achievement of remission (28-joint disease activity score (DAS28) and clinical disease activity index (CDAI)) in unadjusted and adjusted analyses. The persistence of anti-TNF treatment was examined using Cox proportional hazard models. RESULTS: Among 2242 patients (1475 biologically naive, 767 switchers), mACR20, 50 and 70 responses were similar (p>0.05) for adalimumab, etanercept and infliximab at all time points, as were rates of CDAI and DAS28 remission (p>0.05). Response and remission outcomes were consistently inferior for switched versus biologically naive patients. The adjusted OR for achieving an mACR20 response was 0.54 (95% CI 0.38 to 0.76) in first-time switchers and 0.42 (95% CI 0.23 to 0.78) in second-time switchers versus biologically naive patients at 6 months. The adjusted OR for achieving DAS28 remission were 0.29 (95% CI 0.15 to 0.58) for first-time switchers and 0.26 (95% CI 0.08 to 0.84) for second-time switchers. Persistence was higher in biologically naive patients, for whom persistence was highest with infliximab. CONCLUSIONS: No differences in rates of drug response or remission were observed among the three anti-TNF. Infliximab was associated with greater persistence in biologically naive patients. Response, remission and persistence outcomes were diminished for patients who switched anti TNF. PMID- 22294626 TI - Anti-TIF1gamma antibodies (anti-p155) in adult patients with dermatomyositis: comparison of different diagnostic assays. AB - BACKGROUND: A new myositis-specific autoantibody (anti-p155) directed against transcriptional intermediary factor 1 gamma (TIF1gamma) has been described as a good marker of cancer-associated myositis (CAM). OBJECTIVE: To analyse the feasibility of detecting this autoantibody in patient serum samples using new assays with commercially available recombinant TIF1gamma. METHODS: The study included 90 Spanish patients with dermatomyositis (DM), classified as clinically amyopathic DM, CAM, or DM without cancer. Anti-TIF1gamma antibodies were detected by ELISA and immunoblot techniques and compared with anti-p155 antibody detection by protein immunoprecipitation assays with radiolabelled HeLa cells. The kappa coefficient was used to compare the agreement between the different tests. RESULTS: Serum samples from 23 (25.6%) and 20 (22.2%) patients with DM recognised TIF1gamma by ELISA and immunoblot, respectively. ELISA (kappa=0.91) and immunoblot (kappa=0.88) showed excellent agreement with immunoprecipitation analysis (anti-p155). Good concordance (kappa=0.91) was also seen between ELISA and immunoblot. CONCLUSIONS: Excellent agreement was found between anti-p155 detected by immunoprecipitation and anti-TIF1gamma detected by ELISA or immunoblot. These data indicate that identification of this autoantibody can be reliably performed in a standard laboratory setting, with potential application in clinical practice for cancer screening in adult patients with DM. PMID- 22294627 TI - Association between genetic variants in the tumour necrosis factor/lymphotoxin alpha/lymphotoxin beta locus and primary Sjogren's syndrome in Scandinavian samples. AB - OBJECTIVES: Lymphotoxin beta (LTB) has been found to be upregulated in salivary glands of patients with primary Sjogren's syndrome (pSS). An animal model of pSS also showed ablation of the lymphoid organisation and a marked improvement in salivary gland function on blocking the LTB receptor pathway. This study aimed to investigate whether single-nucleotide polymorphisms (SNP) in the lymphotoxin alpha (LTA)/LTB/tumour necrosis factor (TNF) gene clusters are associated with pSS. METHODS: 527 pSS patients and 532 controls participated in the study, all of Caucasian origin from Sweden and Norway. 14 SNP markers were genotyped and after quality control filtering, 12 SNP were analysed for their association with pSS using single marker and haplotype tests, and corrected by permutation testing. RESULTS: Nine markers showed significant association with pSS at the p=0.05 level. Markers rs1800629 and rs909253 showed the strongest genotype association (p=1.64E-11 and p=4.42E-08, respectively, after correcting for sex and country of origin). When the analysis was conditioned for the effect of rs1800629, only the association with rs909253 remained nominally significant (p=0.027). In haplotype analyses the strongest effect was observed for the haplotype rs909253G_rs1800629A (p=9.14E-17). The associations were mainly due to anti-Ro/SSA and anti-La/SSB antibody-positive pSS. CONCLUSIONS: A strong association was found between several SNP in the LTA/LTB/TNFalpha locus and pSS, some of which led to amino acid changes. These data suggest a role for this locus in the development of pSS. Further studies are needed to examine if the genetic effect described here is independent of the known genetic association between HLA and pSS. PMID- 22294628 TI - Differential drug retention between anti-TNF agents and alternative biological agents after inadequate response to an anti-TNF agent in rheumatoid arthritis patients. AB - BACKGROUND: After inadequate response to an antitumour necrosis factor (aTNF) agent for treatment of rheumatoid arthritis (RA), rheumatologists can choose an alternative aTNF or a biological agent with another mode of action (non-aTNF biological (non-aTNF-Bio)). OBJECTIVE: To compare drug retention rates of non aTNF-Bio with alternative aTNF. METHODS: All patients within the Swiss RA cohort (SCQM-RA) treated with an alternative biotherapy after a prior inadequate response to aTNF were analysed. The drug retention of alternative aTNF was compared with non-aTNF-Bio using Cox proportional hazards models, adjusted for potential confounders. RESULTS: 1485 treatment courses after aTNF failure were available for analysis, 853 with alternative aTNF and 632 with non-aTNF-Bio. The median drug retention was 32 months (IQR 14-54) on non-aTNF-Bio versus 21 months (IQR 8-53) on alternative aTNF, or a 50% reduction drug discontinuation risk in favour of non-aTNF-Bio (adjusted hazard ratio (HR) for non-aTNF-Bio: 0.50 (95% CI 0.41 to 0.62)). This effect appears to be modified by the type of prior aTNF failure, with a larger difference in favour of non-aTNF-Bio in patients having experienced a primary failure with a previous aTNF (HR: 0.33 (95% CI 0.24 to 0.47), p<0.001). CONCLUSION: After inadequate response to aTNF, and particularly after primary failure, patients on a non-aTNF-Bio agent have significantly higher drug retention rates. PMID- 22294629 TI - Prevalence and significance of previously undiagnosed rheumatic diseases in pregnancy. AB - OBJECTIVES: The objective of this study was to evaluate the rates of previously undiagnosed rheumatic diseases during the first trimester of pregnancy and their impact on the pregnancy outcome. METHODS: Pregnant women in their first trimester were screened using a two-step approach using a self-administered 10-item questionnaire and subsequent testing for rheumatic autoantibodies (antinuclear antibody, anti-double-stranded DNA, anti-extractable nuclear antigen, anticardiolipin antibodies, anti-beta2-glycoprotein I antibodies and lupus anticoagulant) and evaluation by a rheumatologist. Overall, the complications of pregnancy evaluated included fetal loss, pre-eclampsia, gestational diabetes, fetal growth restriction, delivery at less than 34 weeks, neonatal resuscitation and admission to the neonatal intensive care unit. RESULTS: Out of the 2458 women screened, the authors identified 62 (2.5%) women with previously undiagnosed undifferentiated connective tissue disease (UCTD) and 24 (0.98%) women with previously undiagnosed definite systemic rheumatic disease. The prevalences were seven (0.28%) for systemic lupus erythematosus and Sjogren's syndrome, six (0.24%) for rheumatoid arthritis, three (0.12%) for antiphospholipid syndrome and one (0.04%) for systemic sclerosis. In multiple exact logistic regression, after adjustment for potential confounders, the OR of overall complications of pregnancy were 2.81 (95% CI 1.29 to 6.18) in women with UCTD and 4.57 (95% CI 1.57 to 13.57) in those with definite diseases, respectively, compared with asymptomatic controls. CONCLUSIONS: In our population approximately 2.5% and 1% of first trimester pregnant women had a previously undiagnosed UCTD and definite systemic rheumatic disease, respectively. These conditions were associated with significant negative effects on the outcome of pregnancy. PMID- 22294630 TI - Comparative effectiveness and safety of biological treatment options after tumour necrosis factor alpha inhibitor failure in rheumatoid arthritis: systematic review and indirect pairwise meta-analysis. AB - BACKGROUND: Optimal treatment for rheumatoid arthritis (RA) after inadequate response (IR) to tumour necrosis factor alpha inhibitors (TNFi) remains uncertain. OBJECTIVE: To compare the efficacy and safety of biological agents after TNFi-IR. METHODS: A systematic literature search was carried out using Medline and Cochrane databases, as well as http://www.clinicaltrials.gov, and bibliographies of the retrieved literature were searched by hand. Randomised, placebo-controlled trials that enrolled patients with RA with TNFi-IR were included and American College of Rheumatology (ACR) response as primary efficacy outcome and adverse events (AEs), serious adverse events (SAEs) and serious infections (SIs) as safety measures were extracted. An indirect meta-analysis with pairwise comparisons of efficacy and safety data was then carried out using ORs or risk differences (RDs) in a random effects model. RESULTS: In four randomised controlled trials with 24 weeks' follow-up, direct comparisons of abatacept, golimumab, rituximab and tocilizumab versus placebo showed statistically significant mean ORs of 3.3-8.9 for ACR20, 5.5-10.2 for ACR50 and 4.1-13.5 for ACR70. Risks of AEs, SAEs and SIs versus placebo were non significant. Indirect pairwise comparisons of the four biological agents showed no significant differences in ACR50 and ACR70. Golimumab had a significantly lower OR (0.56-0.59) for ACR20 but significantly fewer AEs (RD 0.13-0.18). Efficacy after one versus multiple TNFi failures did not differ significantly between the different biological agents. CONCLUSION: In patients refractory to one or more TNFi, new biological agents provide significant improvement with good safety. Lacking head-to-head trials, indirect meta-analysis enables a comparison of effectiveness and safety of biological agents with each other and shows that all biological agents have similar effects. PMID- 22294631 TI - Stimulation of soluble guanylate cyclase reduces experimental dermal fibrosis. AB - BACKGROUND: Fibrosis and vascular disease are cardinal features of systemic sclerosis (SSc). Stimulators of soluble guanylate cyclase (sGC) are vasoactive drugs that are currently being evaluated in phase III clinical trials for pulmonary arterial hypertension. OBJECTIVE: To study the antifibrotic potency of sGC stimulators. METHODS: The effect of the sGC stimulator BAY 41-2272 on the release of collagen from dermal fibroblasts was examined. The antifibrotic effects of BAY 41-2272 on prevention and regression of fibrosis in bleomycin induced dermal fibrosis and in Tsk-1 mice were also studied. Telemetric blood pressure studies in conscious mice were used to study potential hypotensive effects of sGC stimulation. RESULTS: sGC stimulation with BAY 41-2272 dose dependently inhibited collagen release in dermal fibroblasts from patients with SSc and healthy individuals. Furthermore, BAY 41-2272 stopped the development of bleomycin-induced dermal fibrosis and skin fibrosis in Tsk-1 mice, preventing dermal and hypodermal thickening, reducing the numbers of myofibroblasts and reducing the hydroxyproline content. In addition, BAY 41-2272 was highly effective in the treatment of established fibrosis in the modified models of bleomycin-induced skin fibrosis and Tsk-1 mice. Treatment with sGC stimulators was well tolerated. Relevant antifibrotic doses of BAY 41-2272 did not affect systemic blood pressure and heart rate in mice. CONCLUSIONS: These findings demonstrate potent antifibrotic effects and good tolerability of sGC stimulators in various experimental models of SSc. Given their potential vasoactive properties, sGC stimulators may be promising candidates for the dual treatment of fibrosis and vascular disease in SSc. PMID- 22294632 TI - Cardiovascular and metabolic risks in psoriasis and psoriatic arthritis: pragmatic clinical management based on available evidence. AB - Several studies suggest that patients with psoriasis and, in particular, psoriatic arthritis (PsA) are at increased risk of cardiovascular disease. These patients are also more likely to be obese and to have diabetes and fatty liver disease. This article discusses the association between psoriasis and PsA and cardiometabolic disorders, emphasising the need for better consideration of simple lifestyle interventions. It also highlights areas for future research and proposes a simple and pragmatic test portfolio to screen for cardiovascular risk and metabolic disorders in patients at higher risk. PMID- 22294633 TI - PAR(2) expression in peripheral blood monocytes of patients with rheumatoid arthritis. AB - OBJECTIVES: Proteinase-activated receptor 2 (PAR(2)) is a G protein-coupled receptor activated by serine proteinases with proinflammatory activity. A study was undertaken to investigate the presence and functional significance of PAR(2) expression on rheumatoid arthritis (RA)-derived leucocyte subsets. METHODS: Venous blood was obtained from patients with RA and osteoarthritis (OA) as well as healthy control subjects. Surface expression of PAR(2) on peripheral blood mononuclear cells (PBMCs) was analysed by flow cytometry and interleukin 6 (IL-6) generation by ELISA. RESULTS: Patients with RA had elevated but variable surface expression of PAR(2) on CD14+ monocytes compared with control subjects (median (1st to 3rd quartiles) 1.76% (0.86-4.10%) vs 0.06% (0.03-0.81%), p<0.0001). CD3+ T cells showed a similar pattern with significantly higher PAR(2) expression in patients with RA compared with controls (3.05% (0.36-11.82%) vs 0.08% (0.02 0.28%), p<0.0001). For both subsets, PAR(2) expression was significantly higher (p<0.00001) in patients with high levels of disease activity: PAR(2) expression for both CD14+ and CD3+ cells correlated to C reactive protein and erythrocyte sedimentation rate. Furthermore, in a cohort of patients with newly diagnosed RA, elevated PAR(2) expression in both CD14+ and CD3+ cells was significantly reduced 3 months after methotrexate or sulfasalazine treatment and this reduction correlated significantly with the reduction in the 28-joint Disease Activity Scale score (p<0.05). PAR(2) expression on cells from patients with OA was low, similar to levels seen in control subjects. Generation of IL-6 by monocytes in response to a selective PAR(2) agonist was significantly greater in patients with RA than in patients with OA and control subjects (p<0.05). CONCLUSIONS: These findings are consistent with a pathogenic role for PAR(2) in RA. PMID- 22294634 TI - Patients with early arthritis who fulfil the 1987 ACR classification criteria for rheumatoid arthritis but not the 2010 ACR/EULAR criteria. PMID- 22294635 TI - Inflamed target tissue provides a specific niche for highly expanded T-cell clones in early human autoimmune disease. AB - OBJECTIVE: To profile quantitatively the T-cell repertoire in multiple joints and peripheral blood of patients with recent onset (early) or established rheumatoid arthritis (RA) using a novel next-generation sequencing protocol to identify potential autoreactive clones. METHODS: Synovium of patients with recent onset (early) RA (<6 months) (n=6) or established RA (>18 months) (n=6) was screened for T-cell clones by sequencing over 10 000 T-cell receptors (TCR) per sample. T cells from paired blood samples were analysed for comparison. From two patients synovial T cells were obtained from multiple inflamed joints. The degree of expansion of each individual clone was based on its unique CDR3 sequence frequency within a sample. Clones with a frequency of over 0.5% were considered to be highly expanded clones (HEC). RESULTS: In early RA synovium, the T-cell repertoire was dominated by 35 HEC (median, range 2-70) accounting for 56% of the TCR sequenced. The clonal dominance in the synovium was patient specific and significantly greater than in established RA (median of 11 HEC (range 5-24) in established RA synovium accounting for 9.8% of T cells; p<0.01). 34% (range 28 40%) of the most expanded T-cell clones were shared between different joints in the same patients, compared with only 4% (range 0-8%) between synovium and blood (p=0.01). CONCLUSIONS: In RA, a systemic autoimmune disease, the inflamed synovium forms a niche for specific expanded T-cell clones, especially in early disease. This suggests that, at least in RA, autoreactive T cells should be addressed specifically in the inflamed tissue, preferably in the early phase of the disease. PMID- 22294636 TI - Polymorphisms of the IgH enhancer HS1.2 and risk of systemic lupus erythematosus. AB - OBJECTIVE: To determine whether the allelic frequency variation of the HS1.2 enhancer of the immunoglobulin heavy chain (IgH) 3' regulatory region (3'RR-1) locus represents a risk factor for systemic lupus erythematosus (SLE) and to identify a possible functional difference in the two most frequent alleles (*1 and *2) in binding nuclear factor- kappaB (NF-kappaB) and Sp1. METHODS: The frequency of the enhancer HS1.2 alleles was determined in two cohorts of patients with SLE (n=293) and in 1185 controls. Electrophoretic mobility shift assays (EMSA) were carried out with B cell nuclear extracts with different probes of HS1.2 alleles *1 and *2 to map the consensus binding sites of the nuclear factors. A confirmatory cohort of 121 patients with SLE was also included. RESULTS: The frequency of allele *2 of the HS1.2 enhancer was significantly increased in patients with SLE compared with controls (OR 1.60, 95% CI 1.33 to 1.92, p<0.001). EMSA experiments showed the presence of the Sp1 binding site in both alleles whereas only allele *2 carried the consensus for the NF-kappaB factor. The presence versus absence of allele *2 in patients with SLE correlated with a higher concentration of IgM levels and with the expression of B cell activating factor receptor (BAFF-R). CONCLUSIONS: The increased frequency of allele *2 in patients with SLE identifies a new genetic risk factor for SLE. A possible biological effect of the polymorphism could be the difference observed in the localisation of an NF-kappaB binding site which is specific for allele *2 and absent in allele *1. These observations suggest a functional effect of the HS1.2 enhancer in this disease. PMID- 22294637 TI - MicroRNA-199a* regulates the expression of cyclooxygenase-2 in human chondrocytes. AB - OBJECTIVE: Cyclooxygenase-2 (COX-2) expression is associated with the pathogenesis of chronic inflammation and pain in osteoarthritis (OA). A study was undertaken to determine whether interleukin-1beta (IL-1beta)-mediated induction of COX-2 can be regulated by microRNAs (miRNAs) in OA. METHODS: Human chondrocytes were stimulated with IL-1beta in vitro. Total RNA was prepared using Trizol reagent. Gene expression was quantified using TaqMan Assays and miRNA targets were identified using bioinformatics. Transfection with reporter construct and premiRNA and antimiRNA was employed to verify suppression of target mRNA. Expression of COX-2 proteins was determined by immunoblotting. The role of activated p38-MAPKs was evaluated using specific inhibitor. RESULTS: The 3'UTR of COX-2 mRNA contained the 'seed-matched' sequences for miR-199a* and miR-101_3. Increased expression of COX-2 correlated with the downregulation of miR-199a* and miR-101_3 in IL-1beta-stimulated normal and OA chondrocytes. miR-199a* directly suppressed the luciferase activity of a COX-2 3'UTR reporter construct and inhibited the IL-1beta-induced expression of COX-2 protein in OA chondrocytes. Modulation of miR-199a* expression also caused significant inhibition of IL-1beta induced upregulation of mPGES1 and prostaglandin E(2) production in OA chondrocytes. Activation of p38-MAPK downregulated the expression of miR-199a* and induced COX-2 expression. Treatment with antimiR-101_3 increased COX-2 expression in IL-1beta-stimulated chondrocytes, but overexpression of miR-101_3 had no significant effect on COX-2 protein expression. CONCLUSIONS: miR-199a* is a direct regulator of COX-2 expression in OA chondrocytes. IL-1beta-induced activation of p38-MAPK correlates inversely with miR199a* expression levels. miR 199a* may be an important regulator of human cartilage homeostasis and a new target for OA therapy. PMID- 22294638 TI - Can flare be predicted in DMARD treated RA patients in remission, and is it important? A cohort study. AB - OBJECTIVES: The treatment target for patients with rheumatoid arthritis (RA) is remission. Imaging techniques and remission criteria may identify patients at risk of flare and associated consequences. This study aimed to determine the clinical, functional and imaging associations of disease flare in patients with RA in remission and any effect on long-term outcomes. METHODS: RA patients in clinical remission as determined by their treating rheumatologist were assessed using clinical, remission criteria, imaging, functional and quality of life measures over 12 months. Flare was defined as any increase in disease activity requiring a change in therapy. RESULTS: 26% of patients (24/93) in remission experienced a flare within 1 year. Fulfilment of remission criteria was not associated with a reduced likelihood of flare. Increased baseline ultrasound power Doppler (PD) activity (unadjusted OR (95% CI) 4.08 (1.26 to 13.19), p=0.014) and functional disability (Health Assessment Questionnaire Disability Index (HAQ-DI) per 0.1 unit1.27 (1.07 to 1.52), p=0.006) were independently associated with risk of flare. Patients who had a flare had significantly worse long-term clinical (Disease Activity Score 28; mean (95% CI) 2.90 (2.55 to 3.24) vs 2.26 (2.06 to 2.46), p=0.002) and functional outcomes (HAQ-DI; 0.412 (0.344 to 0.481) vs 0.322 (0.282 to 0.362), p=0.029) at 12 months compared with patients in sustained remission. CONCLUSION: The presence of PD activity was the most accurate determinant of flare in RA patients in remission. Flare was associated with worse clinical and functional outcomes. These results suggest ultrasound could form an important part of remission assessment in RA. PMID- 22294639 TI - A randomised, double-blind, controlled trial comparing two intra-articular hyaluronic acid preparations differing by their molecular weight in symptomatic knee osteoarthritis. AB - OBJECTIVES: To compare the effects of an intermediate molecular weight (MW) intra articular hyaluronic acid (HA) with a low MW product on knee osteoarthritis (OA) symptoms. METHODS: Patients with symptomatic knee OA were enrolled inarandomised, controlled, double-blind, parallel-group, non-inferiority trial with the possibility to shift to superiority. Patients were randomised to GO-ON(MW 800 1500 kD, 25 mg/2.5 ml) or Hyalgan(MW 500-730 kD, 20 mg/2 ml) injected at 3-weekly intervals. The primary outcome was 6-month change in the WOMAC pain subscale (0 100 mm). Sample size was calculated on a non-inferiority margin of 9 mm, lower than the minimum perceptible clinical improvement. Secondary endpoints included OARSI-OMERACT responder rates RESULTS: The intention-to-treat (ITT) and per protocol (PP) populations consisted of 217 and 209 patients and 171 and 172 patients in the GO-ON and Hyalgan groups, respectively. ITT WOMAC pain of 47.5+/ 1.0(SE) and 48.8+/-1.0 mm decreased by 22.9+/-1.4 mm with GO-ON and 18.4+/-1.5 mm with Hyalgan after 6 months. The primary analysis was conducted in the PP population followed by the ITT population.Mean (95% CI) differences in WOMAC pain change were 5.2 (0.9 to 9.6)mm and 4.5 (0.5 to 8.5)mm, respectively,favouring GO ON, satisfying the claim for non-inferiority (lower limit>-9 mm) and for statistical superiority (95% CI all>0, p=0.021). Ahigher proportion of OARSI/OMERACT responders was observed with GO-ONthan with Hyalgan (73.3% vs58.4%, p=0.001). Both preparations were well tolerated. CONCLUSIONS: Treatment with 3 weekly injections of intermediate MW HA may be superior to low MW HA on knee OA symptoms over 6 months, with similar safety. PMID- 22294640 TI - A high density SNP genotyping approach within the 19q13 chromosome region identifies an association of a CNOT3 polymorphism with ankylosing spondylitis. AB - OBJECTIVE: To identify genomic variants in the 19q13 chromosome region associated with ankylosing spondylitis (AS) in human leucocyte antigen (HLA)-B27-positive populations. METHODS: High-throughput genotyping of 1536 haplotype-tag single nucleotide polymorphisms (SNPs) was performed in 249 patients with AS and 302 healthy controls. Some of the identified associations were validated by genotyping four SNPs in two additional cohorts consisting of 412 cases/301 controls and 144 cases/203 controls. All individuals selected (both cases and controls) were HLA-B27-positive. RESULTS: Two markers in two different genes (CNOT3 and LAIR2) showed significant association (p<10(-3)) with AS. In addition, sliding windows analysis showed association of groups of adjacent SNPs in regions located around CNOT3 (Chr19: 59347459-59356564, p=2.43 * 10(-4) to 6.54 * 10( 4)). The associations were validated by genotyping four SNPs from regions located near LAIR2 and CNOT3 genes (rs1055234, rs8111398, rs2287828 and rs4591276) in two additional cohorts. The CNOT3 polymorphism (rs1055234) remained associated with AS (combined p=9.73 * 10(-6)). One SNP, located downstream of KIR3DL1, was detected which, tested in combination with HLA-Bw4I80, was associated with AS. CONCLUSION: A novel significant association was detected between SNP rs1055234 and AS susceptibility. PMID- 22294641 TI - Sodium oxybate therapy provides multidimensional improvement in fibromyalgia: results of an international phase 3 trial. AB - BACKGROUND: Fibromyalgia is characterised by chronic musculoskeletal pain and multiple symptoms including fatigue, multidimensional function impairment, sleep disturbance and tenderness. Along with pain and fatigue, non-restorative sleep is a core symptom of fibromyalgia. Sodium oxybate (SXB) is thought to reduce non restorative sleep abnormalities. This study evaluated effects of SXB on fibromyalgia-related pain and other symptoms. METHODS: 573 patients with fibromyalgia according to 1990 American College of Rheumatology criteria were enrolled at 108 centres in eight countries. Subjects were randomly assigned to placebo, SXB 4.5 g/night or SXB 6 g/night. The primary efficacy endpoint was the proportion of subjects with >=30% reduction in pain visual analogue scale from baseline to treatment end. Other efficacy assessments included function, sleep quality, effect of sleep on function, fatigue, tenderness, health-related quality of life and subject's impression of change in overall wellbeing. RESULTS: Significant improvements in pain, sleep and other symptoms associated with fibromyalgia were seen in SXB treated subjects compared with placebo. The proportion of subjects with >=30% pain reduction was 42.0% for SXB4.5 g/night (p=0.002) and 51.4% for SXB6 g/night (p<0.001) versus 26.8% for placebo. Quality of sleep (Jenkins sleep scale) improved by 20% for SXB4.5 g/night (p<=0.001) and 25% for SXB6 g/night (p<=0.001) versus 0.5% for placebo. Adverse events with an incidence >=5% and twice placebo were nausea, dizziness, vomiting, insomnia, anxiety, somnolence, fatigue, muscle spasms and peripheral oedema. CONCLUSION: These results, combined with findings from previous phase 2 and 3 studies, provide supportive evidence that SXB therapy affords important benefits across multiple symptoms in subjects with fibromyalgia. PMID- 22294642 TI - Investigation of rheumatoid arthritis susceptibility loci in juvenile idiopathic arthritis confirms high degree of overlap. AB - OBJECTIVES: Rheumatoid arthritis (RA) shares some similar clinical and pathological features with juvenile idiopathic arthritis (JIA); indeed, the strategy of investigating whether RA susceptibility loci also confer susceptibility to JIA has already proved highly successful in identifying novel JIA loci. A plethora of newly validated RA loci has been reported in the past year. Therefore, the aim of this study was to investigate these single nucleotide polymorphisms (SNP) to determine if they were also associated with JIA. METHODS: Thirty-four SNP that showed validated association with RA and had not been investigated previously in the UK JIA cohort were genotyped in JIA cases (n=1242), healthy controls (n=4281), and data were extracted for approximately 5380 UK Caucasian controls from the Wellcome Trust Case-Control Consortium 2. Genotype and allele frequencies were compared between cases with JIA and controls using PLINK. A replication cohort of 813 JIA cases and 3058 controls from the USA was available for validation of any significant findings. RESULTS: Thirteen SNP showed significant association (p<0.05) with JIA and for all but one the direction of association was the same as in RA. Of the eight loci that were tested, three showed significant association in the US cohort. CONCLUSIONS: A novel JIA susceptibility locus was identified, CD247, which represents another JIA susceptibility gene whose protein product is important in T-cell activation and signalling. The authors have also confirmed association of the PTPN2 and IL2RA genes with JIA, both reaching genome-wide significance in the combined analysis. PMID- 22294643 TI - In vitro activity of the siderophore monosulfactam BAL30072 against meropenem-non susceptible Acinetobacter baumannii. AB - OBJECTIVES: The activity of BAL30072 was compared with that of anti-Acinetobacter reference drugs against meropenem-non-susceptible Acinetobacter baumannii isolates associated with up-regulation of the intrinsic OXA-51-like enzyme or an acquired OXA. METHODS: Antimicrobial susceptibility testing was investigated by broth microdilution of 310 non-duplicate, meropenem-non-susceptible A. baumannii isolates to BAL30072, amikacin ampicillin/sulbactam, aztreonam, cefepime, colistin, imipenem, levofloxacin, meropenem, rifampicin, tigecycline and tobramycin. RESULTS: BAL30072 showed greater activity than the beta-lactam comparators, levofloxacin, amikacin, tobramycin and rifampicin. The activity of BAL30072 was comparable to that of tigecycline, with an MIC(50) of 2 mg/L. Elevated BAL30072 MICs were found, but there was no correlation with elevated MICs of the other antimicrobials. CONCLUSIONS: BAL30072 is a promising new agent with good activity against carbapenem-non-susceptible A. baumannii. PMID- 22294644 TI - Plasma IL-6 and IL-9 predict the failure of interferon-alpha plus ribavirin therapy in HIV/HCV-coinfected patients. AB - BACKGROUND: The cytokine profile plays an important role in treatment outcome of hepatitis C virus (HCV) infection, and probably modulates the immune response against HCV. The aim of this study was to evaluate which cytokines affect the response to interferon-alpha (IFN-alpha) and ribavirin therapy and how these cytokines change 72 weeks after starting anti-HCV therapy in HIV/HCV-coinfected patients. METHODS: We carried out a retrospective follow-up study of 65 patients on anti-HCV therapy. A sustained virological response (SVR) was defined as an undetectable HCV viral load up to 24 weeks after the end of treatment. Cytokines were measured using a multiplex immunoassay kit. RESULTS: On starting anti-HCV therapy, non-responder (NR) patients had higher levels of interleukin (IL)-6, IL 9, IL-10 and tumour necrosis factor (TNF)-alpha (P < 0.05), while IL-17A levels were increased in SVR patients (P = 0.058). However, only patients with high levels of IL-6 and IL-9 had decreased odds to achieve SVR (P < 0.05). Plasma levels of IL-6 and IL-9 had a high predictive value for SVR failure [area under the ROC curve (AUC) 0.839 (95% CI 0.733-0.945) and AUC 0.769 (95% CI 0.653 0.884)]. In addition, during anti-HCV therapy, IL-1beta showed an increase in NR patients (P = 0.015) and IL-10 decreased in SVR patients (P = 0.049). After clearing HCV infection, low levels of TNF-alpha, IL-6, IL-9, IL-10, IL-13 and IL 22 were found in SVR patients (P < 0.05), as well as IL-1beta, but only near statistical significance (P = 0.073). CONCLUSIONS: High plasma levels of IL-6 and IL-9 had a high predictive value for SVR failure. Furthermore, clearing of HCV infection was associated with low inflammatory and T helper (Th)2/Th9/Th22 cytokine levels. PMID- 22294646 TI - Impact of IL28B gene polymorphisms on interferon-lambda3 plasma levels during pegylated interferon-alpha/ribavirin therapy for chronic hepatitis C in patients coinfected with HIV. AB - OBJECTIVES: The mechanism explaining the strong association between IL28B rs12979860 polymorphisms and treatment outcome in chronic hepatitis C remains unclear. We explore whether IL28B protein [interferon (IFN)-lambda3] plasma levels may vary according to IL28B genotype and/or following pegylated IFN alpha/ribavirin therapy. PATIENTS AND METHODS: A total of 112 HIV/hepatitis C virus (HCV)-coinfected patients who completed a course of pegylated IFN alpha/ribavirin therapy were examined. Sustained virological response (SVR) was achieved by 56% of patients. IL28B rs12979860 alleles were genotyped using the 5' nuclease assay with specific TaqMan probes. A specific enzyme immunoassay was used to measure IFN-lambda3 plasma levels before initiating anti-HCV therapy and at week 4 of treatment. RESULTS: No significant differences between CC and non-CC IL28B carriers were found at baseline, either in the proportion of patients with detectable IFN-lambda3 plasma levels or in their median values. In contrast, median IFN-lambda3 plasma levels at week 4 of therapy significantly increased with respect to baseline in CC carriers [34.3 (16.7-56.3) versus 15.6 (15.6-30.3) pg/mL, respectively; P < 0.0001], but not in CT/TT carriers. Unexpectedly, increases in IFN-lambda3 at week 4 of therapy did not predict SVR. CONCLUSIONS: The exogenous administration of IFN-alpha may induce IFN-lambda3 release in IL28B CC carriers, but not in CT/TT carriers. However, this finding does not account for the link between IL28B polymorphisms and treatment outcome. PMID- 22294645 TI - Achieving a cure for HIV infection: do we have reasons to be optimistic? AB - The introduction of highly active antiretroviral therapy (HAART) in 1996 has transformed a lethal disease to a chronic pathology with a dramatic decrease in mortality and morbidity of AIDS-related symptoms in infected patients. However, HAART has not allowed the cure of HIV infection, the main obstacle to HIV eradication being the existence of quiescent reservoirs. Several other problems have been encountered with HAART (such as side effects, adherence to medication, emergence of resistance and cost of treatment), and these motivate the search for new ways to treat these patients. Recent advances hold promise for the ultimate cure of HIV infection, which is the topic of this review. Besides these new strategies aiming to eliminate the virus, efforts must be made to improve current HAART. We believe that the cure of HIV infection will not be attained in the short term and that a strategy based on purging the reservoirs has to be associated with an aggressive HAART strategy. PMID- 22294647 TI - Antibiotic pressure compensates the biological cost associated with Pseudomonas aeruginosa hypermutable phenotypes in vitro and in a murine model of chronic airways infection. AB - OBJECTIVES: Hypermutable strains of Pseudomonas aeruginosa frequently emerge during chronic airways infection in cystic fibrosis (CF) patients. While the increased accumulation of mutations by hypermutable strains determines a biological cost for the colonization of secondary environments, the mutator phenotypes might confer a selective advantage under antibiotic treatment in a CF airways environment. METHODS: To test this hypothesis, the reference strain PAO1 and clonal pairs of CF clinical hypermutable and wild-type P. aeruginosa strains belonging to different genotypes were subjected to competition experiments in vitro and in a mouse model of chronic infection. RESULTS: Both in vitro and in vivo, under antibiotic selection pressure, clinical hypermutable P. aeruginosa strains and the reference PAO1DeltamutS outcompeted their wild-type strains, promoting P. aeruginosa hypermutable strains in the airways colonization. This advantage for the hypermutable strain did not occur in the absence of antibiotic treatments. Severe histopathological lesions were detected during chronic murine airways infection after antibiotic pressure, indicating that the advantage of the hypermutable population in the lungs may contribute to disease progression. CONCLUSIONS: Overall, these results showed that P. aeruginosa hypermutability, previously associated with a biological cost, increases colonization potential under selection pressure in a context of CF chronic airways infection and can contribute to lung damage during long-term persistence. PMID- 22294648 TI - A national analysis of complications following hemiarthroplasty for hip fracture in older patients. AB - BACKGROUND: There is emerging evidence that patients with fractured neck of femur (FNOF) aged >85 years have different demands on a health-care system when compared to younger patients. AIM: We sought to better quantify this in terms of comorbidity and complication rates. DESIGN: Retrospective review of national database. METHODS: Data on all patients who underwent hip hemiarthroplasty for FNOF between January 2005 and December 2008 were extracted from the English hospital episode statistics database. RESULTS: There were 41 770 patients aged 65 84 years and 35 321 patients aged >=85 years. The older cohort was less likely to have diabetes, chronic obstructive pulmonary disease and rheumatoid arthritis. However, they exhibited a significantly higher risk of lower respiratory tract infection [odds ratio (OR) = 1.58, 95% confidence interval (CI) 1.50-1.67)], myocardial infarction (OR = 1.67, 1.52-1.83) and acute renal failure (OR = 1.54, 1.40-1.70) within 30 days of surgery with an inpatient mortality risk at 90 days, double that of the younger age group. Length of stay (LoS) was significantly longer in patients >85 years compared to younger patients (median 18 days vs. 15, P < 0.001). CONCLUSION: Patients aged >=85 years admitted for FNOF were found to have a lower incidence of major chronic disease but exhibited a greater incidence of acute events following hemiarthroplasty and their LoS was increased. Targeted medical interventions that focus upon this susceptible patient group may help reduce morbidity and improve survival. PMID- 22294649 TI - Current understanding in HIV immunopathology and treatment. PMID- 22294650 TI - An exceedingly rare type of renal cyst: amoebic cyst. PMID- 22294660 TI - The new UK focus on well-being: what will it mean for tackling social inequalities in health? PMID- 22294661 TI - Healthy convenience: nudging students toward healthier choices in the lunchroom. AB - BACKGROUND: In the context of food, convenience is generally associated with less healthy foods. Given the reality of present-biased preferences, if convenience was associated with healthier foods and less healthy foods were less convenient, people would likely consume healthier foods. This study examines the application of this principle in a school lunchroom where healthier foods were made more convenient relative to less healthy foods. METHODS: One of two lunch lines in a cafeteria was arranged so as to display only healthier foods and flavored milk. Trained field researchers collected purchase and consumption data before and after the conversion. Mean comparisons were used to identify differences in selection and consumption of healthier foods, less healthy foods and chocolate milk. RESULTS: Sales of healthier foods increased by 18% and grams of less healthy foods consumed decreased by nearly 28%. Also, healthier foods' share of total consumption increased from 33 to 36%. Lastly, we find that students increased their consumption of flavored milk, but flavored milk's share of total consumption did not increase. CONCLUSIONS: In a school lunchroom, a convenience line that offered only healthier food options nudged students to consume fewer unhealthy foods. This result has key implications for encouraging healthy behavior in public schools nation wide, cafeterias and other food establishments. PMID- 22294662 TI - Comprehensive evaluation of canonical versus Dicer-substrate siRNA in vitro and in vivo. AB - Since the discovery of RNA interference (RNAi), researchers have identified a variety of small interfering RNA (siRNA) structures that demonstrate the ability to silence gene expression through the classical RISC-mediated mechanism. One such structure, termed "Dicer-substrate siRNA" (dsiRNA), was proposed to have enhanced potency via RISC-mediated gene silencing, although a comprehensive comparison of canonical siRNAs and dsiRNAs remains to be described. The present study evaluates the in vitro and in vivo activities of siRNAs and dsiRNAs targeting Phosphatase and Tensin Homolog (PTEN) and Factor VII (FVII). More than 250 compounds representing both siRNA and dsiRNA structures were evaluated for silencing efficacy. Lead compounds were assessed for duration of silencing and other key parameters such as cytokine induction. We identified highly active compounds from both canonical siRNAs and 25/27 dsiRNAs. Lead compounds were comparable in potency both in vitro and in vivo as well as duration of silencing in vivo. Duplexes from both structural classes tolerated 2'-OMe chemical modifications well with respect to target silencing, although some modified dsiRNAs demonstrated reduced activity. On the other hand, dsiRNAs were more immunostimulatory as compared with the shorter siRNAs, both in vitro and in vivo. Because the dsiRNA structure does not confer any appreciable benefits in vitro or in vivo while demonstrating specific liabilities, further studies are required to support their applications in RNAi therapeutics. PMID- 22294663 TI - Cow's milk allergy and rolandic epilepsy: a close relationship? PMID- 22294664 TI - Interventions to reduce acute paediatric hospital admissions: a systematic review. AB - OBJECTIVE: To compare the effectiveness of interventions aimed at reducing the rate of acute paediatric hospital admissions. DESIGN: Systematic review. DATA SOURCES: Medline, Embase, PsychINFO, The Cochrane Library, Science Citation Index Expanded from inception to September 2010; hand searches of the reference lists of included papers and other review papers identified in the search. REVIEW METHODS: Controlled trials were included. Articles were screened for inclusion independently by two reviewers. Data extraction and quality appraisal were performed by one reviewer and checked by a second with discrepancies resolved by discussion with a third if necessary. RESULTS: Seven papers were included. There is some evidence to suggest that short stay units may reduce admission rates. However, there is a general lack of detail in the reporting of interventions and the methods used in their evaluation which precludes detailed interpretation and extrapolation of the results. The authors found no evidence that the use of algorithms and guidelines to manage the admission decision was effective in reducing acute admission rates. Furthermore, the authors were unable to locate any eligible papers reporting the effects on admission rates of admission decision by paediatric consultant, telephone triage by paediatric consultant or the establishment of next day emergency paediatric clinics. CONCLUSION: There is little published evidence upon which to base an optimal strategy for reducing paediatric admission rates. The evidence that does exist is subject to substantial bias. There is a pressing need for high quality, well conducted research to enable informed service change. PMID- 22294665 TI - 'Asthma' cured after cardiac surgery. PMID- 22294666 TI - Infant botulism and botulism immune globulin in the UK: a case series of four infants. PMID- 22294667 TI - Body composition in children with type 1 diabetes in the first year after diagnosis: relationship to glycaemic control and cardiovascular risk. AB - INTRODUCTION: Rapid weight gain is often observed following initiation of insulin therapy in children with type 1 diabetes mellitus (T1DM) and girls are particularly at risk of becoming overweight. The authors evaluated body composition changes in children during the first year after diagnosis and related this to markers of cardiovascular risk. METHODS: Body mass index (BMI) and body composition measured by whole body dual energy x-ray absorptiometry (DEXA) were assessed in 30 patients (18 boys) with T1DM 3-10 days after diagnosis, 6 weeks later and at 1 year, and on two occasions 1 year apart in 14 controls (8 boys). Cardiovascular risk markers were assessed in T1DM subjects at 1 year. RESULTS: T1DM subjects had lower BMI SD scores (SDS) at diagnosis than controls (mean (SD) BMI SDS -0.67 (1.34) vs 0.20 (1.14), p<0.05) and reduced percentage body fat (20.3% (4.6) vs 24.5% (7.7), p<0.05). T1DM subjects normalised their body composition at 6 weeks and this was maintained 1 year later. Girls with diabetes were thinner than boys at diagnosis (BMI SDS -1.64 (1.02) vs -0.02 (1.17), p<0.05) and at 1 year (BMI SDS -0.58(0.9) vs 0.65 (0.98), p<0.05). Girls had higher glycated haemoglobin (HbA1c) (8.8% (1.2) vs 7.8% (1.0), p<0.05), insulin dose (1.01 (0.30) vs 0.82 (0.18) U/kg/day, p=0.04), total cholesterol (4.30 (0.45) vs 3.79 (0.50) mmol/l, p<0.05) and high-density lipoprotein (2.62 (0.53) vs 2.02 (0.37) mmol/l). High sensitivity C reactive protein and fibrinogen were in the normal range and there were no differences between genders. DISCUSSION: Insulin deficiency at diagnosis of diabetes causes a catabolic state that is predominantly lipolytic. Body composition normalises within 6 weeks of treatment, though girls remain thinner than boys both at diagnosis and 1 year thereafter, in contrast to published findings. Despite girls being prescribed a larger insulin dose, their HbA1c and cholesterol levels are higher at 1 year suggesting increased insulin resistance and cardiovascular risk. PMID- 22294668 TI - A randomised controlled trial of Hartmann's solution versus half normal saline in postoperative paediatric spinal instrumentation and craniotomy patients. AB - OBJECTIVE: To compare the difference in plasma sodium at 16-18 h following major surgery in children who were prescribed either Hartmann's and 5% dextrose or 0.45% saline and 5% dextrose. DESIGN: A prospective, randomised, open label study. SETTING: The paediatric intensive care unit (650 admissions per annum) in a tertiary children's hospital in Brisbane, Australia. PATIENTS: The study group comprised 82 children undergoing spinal instrumentation, craniotomy for brain tumour resection, or cranial vault remodelling. INTERVENTIONS: Patients received either Hartmann's and 5% dextrose at full maintenance rate or 0.45% saline and 5% dextrose at two-thirds maintenance rate. MAIN OUTCOMES MEASURES: PRIMARY OUTCOME MEASURE: plasma sodium at 16-18 h postoperatively; secondary outcome measure: number of fluid boluses administered. RESULTS: Mean postoperative plasma sodium levels of children receiving 0.45% saline and 5% dextrose were 1.4 mmol/l (95% CI 0.4 to 2.5) lower than those receiving Hartmann's and 5% dextrose (p=0.008). In the 0.45% saline group, seven patients (18%) became hyponatraemic (Na <135 mmol/l) at 16-18 h postoperatively; in the Hartmann's group no patient became hyponatraemic (p=0.01). No child in either fluid group became hypernatraemic. CONCLUSIONS: The postoperative fall in plasma sodium was smaller in children who received Hartmann's and 5% dextrose compared to those who received 0.45% saline and 5% dextrose. It is suggested that Hartmann's and 5% dextrose should be administered at full maintenance rate postoperatively to children who have undergone major surgery in preference to hypotonic fluids. PMID- 22294669 TI - Specific antibody deficiency in children with chronic wet cough. AB - The prevalence and clinical significance of specific polysaccharide antibody deficiency (SAD) in children are poorly understood. The authors sought to determine the prevalence of SAD in children with chronic wet cough, through a retrospective study of all children with chronic wet cough attending our tertiary respiratory clinic over a 12-month period. Antibody levels to 13 pneumococcal serotypes were measured following vaccination with the unconjugated pneumococcal polysaccharide vaccine, Pneumovax II, and clinical data were reviewed. Twenty four children over 2 years of age with chronic wet cough were vaccinated. Fourteen (58%) failed to mount an adequate antibody response, consistent with SAD. Children with SAD were more likely than children with normal antibody responses to require intravenous antibiotics (p=0.035) and to have abnormal chest radiographs (p=0.029). The authors conclude that SAD is present in a significant number of children with chronic wet cough. The clinical significance and long term outcome of SAD warrant further investigation in prospective studies. PMID- 22294670 TI - Paediatric sepsis-like illness and human parechovirus. PMID- 22294671 TI - The role of cystovaginoscopy and hygienic advice in girls referred for symptoms of vulvovaginitis. AB - Vulvovaginitis is a common presenting symptom referred to a paediatric urology clinic. Some of these patients undergo diagnostic cystovaginoscopy to determine whether there is any underlying anatomical cause for the persistent infection. However, in the majority of the patients, no underlying abnormality is found and they are given hygienic advice and prescribed bio yoghurt postoperatively. This study examines the outcome in these patients after hygienic advice is given: determining whether cystovaginoscopy was really necessary and whether it changed the management of vulvovaginitis. PMID- 22294672 TI - On the covariate-adjusted estimation for an overall treatment difference with data from a randomized comparative clinical trial. AB - To estimate an overall treatment difference with data from a randomized comparative clinical study, baseline covariates are often utilized to increase the estimation precision. Using the standard analysis of covariance technique for making inferences about such an average treatment difference may not be appropriate, especially when the fitted model is nonlinear. On the other hand, the novel augmentation procedure recently studied, for example, by Zhang and others (2008. Improving efficiency of inferences in randomized clinical trials using auxiliary covariates. Biometrics 64, 707-715) is quite flexible. However, in general, it is not clear how to select covariates for augmentation effectively. An overly adjusted estimator may inflate the variance and in some cases be biased. Furthermore, the results from the standard inference procedure by ignoring the sampling variation from the variable selection process may not be valid. In this paper, we first propose an estimation procedure, which augments the simple treatment contrast estimator directly with covariates. The new proposal is asymptotically equivalent to the aforementioned augmentation method. To select covariates, we utilize the standard lasso procedure. Furthermore, to make valid inference from the resulting lasso-type estimator, a cross validation method is used. The validity of the new proposal is justified theoretically and empirically. We illustrate the procedure extensively with a well-known primary biliary cirrhosis clinical trial data set. PMID- 22294675 TI - Science should be in the public domain. AB - Variants of avian influenza H5N1 virus that are transmitted by the airborne route among ferrets have been identified. The National Science Advisory Board for Biosecurity has advised against publication of the details of the methods used to obtain these viruses and the amino acid changes that lead to transmission in ferrets. This decision is not based on sound scientific principles and risks setting a precedent that will make it easier to put in place highly restrictive regulations on scientific research and publication. PMID- 22294676 TI - Mammalian-transmissible H5N1 influenza: the dilemma of dual-use research. AB - The National Science Advisory Board for Biosecurity (NSABB)'s recommendation to restrict publication of the details of the generation of mammalian-transmissible H5N1 influenza virus is unprecedented. Dual-use considerations indicated that the potential biosecurity risks of a transmissible H5N1 virus with a possible mortality of 50% in humans outweigh the substantial benefits of open and complete scientific exchange in this case, although the benefits include potential early detection strategies for H5N1 viruses with specific genetic markers and control strategies, including development of antivirals and vaccines. It is argued that both the funding agency (the National Institute of Allergy and Infectious Diseases) and the scientists were responding to societal needs and acted entirely responsibly. These studies usher in a new era for life sciences, compelling the research community to confront important decisions: under what conditions should such research be done? How can the principle of full release of information be balanced with the moral imperative to protect the public health? PMID- 22294677 TI - The NSABB recommendations: rationale, impact, and implications. AB - The National Science Advisory Board for Biosecurity (NSABB) has recommended that two scientific papers concerning the laboratory adaptation of avian H5N1 influenza virus to mammal-to-mammal respiratory transmission restrict their content to prevent others from replicating their work. After hearing from experts in the field of influenza research and public health, the benefits of the research were deemed less important than the potential negative consequences. The evaluation followed established NSABB procedures and prior policy recommendations for identifying dual use research of concern (DURC). This recommendation was received by the United States Government, endorsed and forwarded to the research teams and scientific journals involved with the publications. PMID- 22294678 TI - The H5N1 manuscript redaction controversy. PMID- 22294679 TI - Natural competence is a major mechanism for horizontal DNA transfer in the oral pathogen Porphyromonas gingivalis. AB - Porphyromonas gingivalis is a Gram-negative anaerobe that resides exclusively in the human oral cavity. Long-term colonization by P. gingivalis requires the bacteria to evade host immune responses while adapting to the changing host physiology and alterations in the composition of the oral microflora. The genetic diversity of P. gingivalis appears to reflect the variability of its habitat; however, little is known about the molecular mechanisms generating this diversity. Previously, our research group established that chromosomal DNA transfer occurs between P. gingivalis strains. In this study, we examine the role of putative DNA transfer genes in conjugation and transformation and demonstrate that natural competence mediated by comF is the dominant form of chromosomal DNA transfer, with transfer by a conjugation-like mechanism playing a minor role. Our results reveal that natural competence mechanisms are present in multiple strains of P. gingivalis, and DNA uptake is not sensitive to DNA source or modification status. Furthermore, extracellular DNA was observed for the first time in P. gingivalis biofilms and is predicted to be the major DNA source for horizontal transfer and allelic exchange between strains. We propose that exchange of DNA in plaque biofilms by a transformation-like process is of major ecological importance in the survival and persistence of P. gingivalis in the challenging oral environment. IMPORTANCE: P. gingivalis colonizes the oral cavities of humans worldwide. The long-term persistence of these bacteria can lead to the development of chronic periodontitis and host morbidity associated with tooth loss. P. gingivalis is a genetically diverse species, and this variability is believed to contribute to its successful colonization and survival in diverse human hosts, as well as evasion of host immune defenses and immunization strategies. We establish here that natural competence is the major driving force behind P. gingivalis DNA exchange and that conjugative DNA transfer plays a minor role. Furthermore, we reveal for the first time the presence of extracellular DNA in P. gingivalis biofilms, which is most likely the source of DNA exchanged between strains within dental plaque. These studies expand our understanding of the mechanisms used by this important member of the human oral flora to transition its relationship with the host from a commensal to a pathogenic relationship. PMID- 22294680 TI - Novel transporter required for biogenesis of cbb3-type cytochrome c oxidase in Rhodobacter capsulatus. AB - The acquisition, delivery, and incorporation of metals into their respective metalloproteins are important cellular processes. These processes are tightly controlled in order to prevent exposure of cells to free-metal concentrations that could yield oxidative damage. Copper (Cu) is one such metal that is required as a cofactor in a variety of proteins. However, when present in excessive amounts, Cu is toxic due to its oxidative capability. Cytochrome c oxidases (Coxs) are among the metalloproteins whose assembly and activity require the presence of Cu in their catalytic subunits. In this study, we focused on the acquisition of Cu for incorporation into the heme-Cu binuclear center of the cbb(3)-type Cox (cbb(3)-Cox) in the facultative phototroph Rhodobacter capsulatus. Genetic screens identified a cbb(3)-Cox defective mutant that requires Cu(2+) supplementation to produce an active cbb(3)-Cox. Complementation of this mutant using wild-type genomic libraries unveiled a novel gene (ccoA) required for cbb(3)-Cox biogenesis. In the absence of CcoA, the cellular Cu content decreases and cbb(3)-Cox assembly and activity become defective. CcoA shows homology to major facilitator superfamily (MFS)-type transporter proteins. Members of this family are known to transport small solutes or drugs, but so far, no MFS protein has been implicated in cbb(3)-Cox biogenesis. These findings provide novel insights into the maturation and assembly of membrane-integral metalloproteins and on a hitherto-unknown function(s) of MFS-type transporters in bacterial Cu acquisition. IMPORTANCE: Biogenesis of energy-transducing membrane integral enzymes, like the heme copper-containing cytochrome c oxidases, and the acquisition of transition metals, like copper, as their catalytic cofactors are vital processes for all cells. These widespread and well-controlled processes are poorly understood in all organisms, including bacteria. Defects in these processes lead to severe mitochondrial diseases in humans and poor crop yields in plants. In this study, using the facultative phototroph Rhodobacter capsulatus as a model organism, we report on the discovery of a novel major facilitator superfamily (MFS)-type transporter (CcoA) that affects cellular copper content and cbb(3)-type cytochrome c oxidase production in bacteria. PMID- 22294681 TI - Manuka honey inhibits the development of Streptococcus pyogenes biofilms and causes reduced expression of two fibronectin binding proteins. AB - Streptococcus pyogenes (group A Streptococcus; GAS) is always of clinical significance in wounds where it can initiate infection, destroy skin grafts and persist as a biofilm. Manuka honey has broad spectrum antimicrobial activity and its use in the clinical setting is beginning to gain acceptance with the continuing emergence of antibiotic resistance and the inadequacy of established systemic therapies; novel inhibitors may affect clinical practice. In this study, the effect of manuka honey on S. pyogenes (M28) was investigated in vitro with planktonic and biofilm cultures using MIC, MBC, microscopy and aggregation efficiency. Bactericidal effects were found in both planktonic cultures and biofilms, although higher concentrations of manuka honey were needed to inhibit biofilms. Abrogation of adherence and intercellular aggregation was observed. Manuka honey permeated 24 h established biofilms of S. pyogenes, resulting in significant cell death and dissociation of cells from the biofilm. Sublethal concentrations of manuka honey effectively prevented the binding of S. pyogenes to the human tissue protein fibronectin, but did not inhibit binding to fibrinogen. The observed inhibition of fibronectin binding was confirmed by a reduction in the expression of genes encoding two major fibronectin-binding streptococcal surface proteins, Sof and SfbI. These findings indicate that manuka honey has potential in the topical treatment of wounds containing S. pyogenes. PMID- 22294682 TI - The impact of epicardial fat volume on coronary plaque vulnerability: insight from optical coherence tomography analysis. AB - AIMS: Epicardial fat volume (EFV) has been implicated in coronary artery disease. Relationship between EFV and coronary plaque vulnerability has not been elucidated. The aim of this study was to investigate the association of EFV with coronary plaque vulnerability by using optical coherence tomography (OCT). METHODS AND RESULTS: We enrolled 117 patients who underwent multislice computed tomography (MSCT) and OCT. EFV was quantified on MSCT. Patients were categorized according to tertiles of EFV: low tertile, EFV < 104.1 cm(3); mid-tertile, 104.1 cm(3)<= EFV <= 130.7 cm(3); high tertile, EFV > 130.7 cm(3). A total of 180 vessels and 221 plaques were assessed with OCT to detect a thin-capped fibroatheroma (TCFA). TCFA was defined as a plaque with necrotic lipid pools >= 2 quadrants and minimum fibrous cap thickness measuring <65 MUm. Patients with low computed tomographic attenuation and positive remodelling were frequently observed and patients with OCT-derived TCFA were more common in the high tertile EFV. EFV was associated with a maximal lipid arc (103.4 +/- 28.2 cm(3) in 0 quadrant, 120.2 +/- 35.2 cm(3) in 1-2 quadrants, and 131.5 +/- 41.1 cm(3) in >2 quadrants; P= 0.01) and inversely correlated with a minimum fibrous cap thickness of the patients (r = -0.400, P<0.01). In multivariate analysis, the high tertile of EFV remained an independent predictor for patients with OCT-derived TCFA [odds ratio (OR) 2.92; 95% confidence interval (CI) 1.13-7.55; P= 0.027] and acute coronary syndrome (ACS) patients (OR 2.89; 95% CI 1.14-7.29; P= 0.025). CONCLUSION: EFV was associated with coronary plaque vulnerability and high EFV was an independent predictor of ACS in patients with coronary artery disease. PMID- 22294683 TI - The association of clinical outcome with right atrial and ventricular remodelling in patients with pulmonary arterial hypertension: study with real-time three dimensional echocardiography. AB - AIMS: Right atrial (RA) dilatation may be important for patients' outcome in pulmonary arterial hypertension (PAH). The aim of this study was to examine the longitudinal RA and right ventricular (RV) remodelling in PAH patients using real time three-dimensional echocardiography (3DE) and their relation to clinical outcome. METHODS AND RESULTS: Sixty-two consecutive PAH patients were studied and compared with a control group of 30 healthy volunteers. RA and RV sphericity indices were measured with 3DE. RV ejection fraction (RVEF), RA volume (RAvol), and the quantification of jet area of tricuspid regurgitation (TR) were measured. Two observers were used for reproducibility assessment. The geometrical change of RA and RV was assessed in relation to clinical outcome, as defined by the increase of functional class or admission to the hospital due to right heart failure. Over 1 year of follow-up, there was significant increase of RA sphericity index (0.85+/-0.16 vs. 1.2+/-0.24, P<0.01), RV dilatation (RV sphericity index 0.71+/-0.07 vs. 0.98+/-0.04, P<0.01), as well as deterioration of RV systolic function (RVEF 33+/-8.2 vs. 28+/-7.6%, P<0.01). Twenty-three patients (37%) had a clinical deterioration within 1 year. An increase of RA sphericity index>0.24 predicted clinical deterioration with a sensitivity of 96% and a specificity of 90% [area under the curve (AUC) 0.97]. RV sphericity index was less sensitive (70%) and specific (62%) in predicting clinical deterioration (AUC 0.649). The deterioration in RVEF had a sensitivity of 91.1% and a specificity of 35.3% (AUC 0.479) in predicting clinical deterioration. The dilatation of RA>14 mL over 1 year had high sensitivity at 82.6% but low specificity at 30.8% in predicting clinical deterioration. CONCLUSION: PAH leads to RA and RV dilatation and functional deterioration which are linked to an adverse clinical outcome. 3DE measurement of RA sphericity index may be a suitable index in predicting clinical deterioration of PAH patients. PMID- 22294684 TI - Stone heart or apical retraction and calcification in Chagas' cardiomyopathy. PMID- 22294685 TI - Nurr1 protein is required for N-methyl-D-aspartic acid (NMDA) receptor-mediated neuronal survival. AB - NMDA receptor (NMDAR) stimulation promotes neuronal survival during brain development. Cerebellar granule cells (CGCs) need NMDAR stimulation to survive and develop. These neurons differentiate and mature during its migration from the external granular layer to the internal granular layer, and lack of excitatory inputs triggers their apoptotic death. It is possible to mimic this process in vitro by culturing CGCs in low KCl concentrations (5 mm) in the presence or absence of NMDA. Using this experimental approach, we have obtained whole genome expression profiles after 3 and 8 h of NMDA addition to identify genes involved in NMDA-mediated survival of CGCs. One of the identified genes was Nurr1, a member of the orphan nuclear receptor subfamily Nr4a. Our results report a direct regulation of Nurr1 by CREB after NMDAR stimulation. ChIP assay confirmed CREB binding to Nurr1 promoter, whereas CREB shRNA blocked NMDA-mediated increase in Nurr1 expression. Moreover, we show that Nurr1 is important for NMDAR survival effect. We show that Nurr1 binds to Bdnf promoter IV and that silencing Nurr1 by shRNA leads to a decrease in brain-derived neurotrophic factor (BDNF) protein levels and a reduction of NMDA neuroprotective effect. Also, we report that Nurr1 and BDNF show a similar expression pattern during postnatal cerebellar development. Thus, we conclude that Nurr1 is a downstream target of CREB and that it is responsible for the NMDA-mediated increase in BDNF, which is necessary for the NMDA-mediated prosurvival effect on neurons. PMID- 22294686 TI - Human alpha/beta hydrolase domain containing 10 (ABHD10) is responsible enzyme for deglucuronidation of mycophenolic acid acyl-glucuronide in liver. AB - Mycophenolic acid (MPA), the active metabolite of the immunosuppressant mycophenolate mofetil (MMF), is primarily metabolized by glucuronidation to a phenolic glucuronide (MPAG) and an acyl glucuronide (AcMPAG). It is known that AcMPAG, which may be an immunotoxic metabolite, is deglucuronidated in human liver. However, it has been reported that recombinant beta-glucuronidase does not catalyze this reaction. AcMPAG deglucuronidation activity was detected in both human liver cytosol (HLC) and microsomes (HLM). In this study, the enzyme responsible for AcMPAG deglucuronidation was identified by purification from HLC with column chromatographic purification steps. The purified enzyme was identified as alpha/beta hydrolase domain containing 10 (ABHD10) by amino acid sequence analysis. Recombinant ABHD10 expressed in Sf9 cells efficiently deglucuronidated AcMPAG with a K(m) value of 100.7 +/- 10.2 MUM, which was similar to those in HLM, HLC, and human liver homogenates (HLH). Immunoblot analysis revealed ABHD10 protein expression in both HLC and HLM. The AcMPAG deglucuronidation by recombinant ABHD10, HLC, and HLH were potently inhibited by AgNO(3), CdCl(2), CuCl(2), PMSF, bis-p-nitrophenylphosphate, and DTNB. The CL(int) value of AcMPAG formation from MPA, which was catalyzed by human UGT2B7, in HLH was increased by 1.8-fold in the presence of PMSF. Thus, human ABHD10 would affect the formation of AcMPAG, the immunotoxic metabolite. PMID- 22294687 TI - Crystal structures and small-angle x-ray scattering analysis of UDP galactopyranose mutase from the pathogenic fungus Aspergillus fumigatus. AB - UDP-galactopyranose mutase (UGM) is a flavoenzyme that catalyzes the conversion of UDP-galactopyranose to UDP-galactofuranose, which is a central reaction in galactofuranose biosynthesis. Galactofuranose has never been found in humans but is an essential building block of the cell wall and extracellular matrix of many bacteria, fungi, and protozoa. The importance of UGM for the viability of many pathogens and its absence in humans make UGM a potential drug target. Here we report the first crystal structures and small-angle x-ray scattering data for UGM from the fungus Aspergillus fumigatus, the causative agent of aspergillosis. The structures reveal that Aspergillus UGM has several extra secondary and tertiary structural elements that are not found in bacterial UGMs yet are important for substrate recognition and oligomerization. Small-angle x-ray scattering data show that Aspergillus UGM forms a tetramer in solution, which is unprecedented for UGMs. The binding of UDP or the substrate induces profound conformational changes in the enzyme. Two loops on opposite sides of the active site move toward each other by over 10 A to cover the substrate and create a closed active site. The degree of substrate-induced conformational change exceeds that of bacterial UGMs and is a direct consequence of the unique quaternary structure of Aspergillus UGM. Galactopyranose binds at the re face of the FAD isoalloxazine with the anomeric carbon atom poised for nucleophilic attack by the FAD N5 atom. The structural data provide new insight into substrate recognition and the catalytic mechanism and thus will aid inhibitor design. PMID- 22294688 TI - G-protein-coupled receptor kinase interactor-1 (GIT1) is a new endothelial nitric oxide synthase (eNOS) interactor with functional effects on vascular homeostasis. AB - Endothelial cell nitric-oxide (NO) synthase (eNOS), the enzyme responsible for synthesis of NO in the vasculature, undergoes extensive post-translational modifications that modulate its activity. Here we have identified a novel eNOS interactor, G-protein-coupled receptor (GPCR) kinase interactor-1 (GIT1), which plays an unexpected role in GPCR stimulated NO signaling. GIT1 interacted with eNOS in the endothelial cell cytoplasm, and this robust association was associated with stimulatory eNOS phosphorylation (Ser(1177)), enzyme activation, and NO synthesis. GIT1 knockdown had the opposite effect. Additionally, GIT1 expression was reduced in sinusoidal endothelial cells after liver injury, consistent with previously described endothelial dysfunction in this disease. Re expression of GIT1 after liver injury rescued the endothelial phenotype. These data emphasize the role of GPCR signaling partners in eNOS function and have fundamental implications for vascular disorders involving dysregulated eNOS. PMID- 22294689 TI - Genome-wide repression of NF-kappaB target genes by transcription factor MIBP1 and its modulation by O-linked beta-N-acetylglucosamine (O-GlcNAc) transferase. AB - The transcription factor c-MYC intron binding protein 1 (MIBP1) binds to various genomic regulatory regions, including intron 1 of c-MYC. This factor is highly expressed in postmitotic neurons in the fetal brain and may be involved in various biological steps, such as neurological and immunological processes. In this study, we globally characterized the transcriptional targets of MIBP1 and proteins that interact with MIBP1. Microarray hybridization followed by gene set enrichment analysis revealed that genes involved in the pathways downstream of MYC, NF-kappaB, and TGF-beta were down-regulated when HEK293 cells stably overexpressed MIBP1. In silico transcription factor binding site analysis of the promoter regions of these down-regulated genes showed that the NF-kappaB binding site was the most overrepresented. The up-regulation of genes known to be in the NF-kappaB pathway after the knockdown of endogenous MIBP1 in HT1080 cells supports the view that MIBP1 is a down-regulator of the NF-kappaB pathway. We also confirmed the binding of the MIBP1 to the NF-kappaB site. By immunoprecipitation and mass spectrometry, we detected O-linked beta-N acetylglucosamine (O-GlcNAc) transferase as a prominent binding partner of MIBP1. Analyses using deletion mutants revealed that a 154-amino acid region of MIBP1 was necessary for its O-GlcNAc transferase binding and O-GlcNAcylation. A luciferase reporter assay showed that NF-kappaB-responsive expression was repressed by MIBP1, and stronger repression by MIBP1 lacking the 154-amino acid region was observed. Our results indicate that the primary effect of MIBP1 expression is the down-regulation of the NF-kappaB pathway and that this effect is attenuated by O-GlcNAc signaling. PMID- 22294690 TI - Mutated major histocompatibility complex class II transactivator up-regulates interleukin-33-dependent differentiation of Th2 subset through Nod2 binding for NLR (NOD-like receptor) signaling initiation. AB - Dominant-negative mutants of class II transactivator (mCIITAs) with N-terminal depletion have been used to repress the transcription of class II genes in xenotransplantation. Here, we report that mCIITA overexpressing myeloid cell line Ana-1 (Ana-1-mCIITA) derived from a C57BL/6 mouse was able to down-regulate the MHC class II expression and reverse immune responses from Th1 (IL-2(+)IFN gamma(+)STAT4(+)) to Th2 (IL-4(+)IL-5(+)IL-10(+)IL-13(+)STAT6(+)) when cocultured with T cells. Mechanism analysis indicated that the mCIITA protein is able to initiate a NOD-like receptor-related signaling pathway via binding of the cytoplasmic Nod2 protein, which was followed by activating RIP2, caspase 1, and IKK-alpha/beta. This ensures the expression of the genes encoding the cytokines IL-33, IL-1beta, and TNF-alpha; however, only the highly expressed IL-33 is responsible for inducing the type 2 response, with a skewed Th2 cytokine secretion (IL-4(+)IL-5(+)IL-10(+)IL-13(+)IL-2(-)IFN-gamma(-)), which was completely prevented by the deactivation of the Nod2 gene with siRNA or by the blockage of the IL-33-related signaling using the mAb ST2L against the IL-33 receptor. mCIITA-mediated Th2 conversion was also successfully induced in vivo in a mCIITA-transgenic C57BL/6 mouse model. These results indicate that the Th1/Th2 balance could be regulated by an N terminus-depleted CIITA molecule via NOD-like receptor-related signaling, a property valuable for disease control, especially for inducing transplantation tolerance via the repression of class II expression and the attenuation of a Th1-dominant response. PMID- 22294691 TI - MicroRNA profile of circulating CD4-positive regulatory T cells in human adults and impact of differentially expressed microRNAs on expression of two genes essential to their function. AB - Regulatory T cells (Tregs) are characterized by a high expression of IL-2 receptor alpha chain (CD25) and of forkhead box P3 (FOXP3), the latter being essential for their development and function. Another major player in the regulatory function is the cytotoxic T-lymphocyte associated molecule-4 (CTLA-4) that inhibits cytotoxic responses. However, the regulation of CTLA-4 expression remains less well explored. We therefore studied the microRNA signature of circulating CD4(+) Tregs isolated from adult healthy donors and identified a signature composed of 15 differentially expressed microRNAs. Among those, miR-24, miR-145, and miR-210 were down-regulated in Tregs compared with controls and were found to have potential target sites in the 3'-UTR of FOXP3 and CTLA-4; miR-24 and miR-210 negatively regulated FOXP3 expression by directly binding to their two target sites in its 3'-UTR. On the other hand, miR-95, which is highly expressed in adult peripheral blood Tregs, positively regulated FOXP3 expression via an indirect mechanism yet to be identified. Finally, we showed that miR-145 negatively regulated CTLA-4 expression in human CD4(+) adult peripheral blood Tregs by binding to its target site in CTLA-4 transcript 3'-UTR. To our knowledge, this is the first identification of a human adult peripheral blood CD4(+) Treg microRNA signature. Moreover, unveiling one mechanism regulating CTLA 4 expression is novel and may lead to a better understanding of the regulation of this crucial gene. PMID- 22294692 TI - Increasing serum half-life and extending cholesterol lowering in vivo by engineering antibody with pH-sensitive binding to PCSK9. AB - Target-mediated clearance and high antigen load can hamper the efficacy and dosage of many antibodies. We show for the first time that the mouse, cynomolgus, and human cross-reactive, antagonistic anti-proprotein convertase substilisin kexin type 9 (PCSK9) antibodies J10 and the affinity-matured and humanized J16 exhibit target-mediated clearance, resulting in dose-dependent pharmacokinetic profiles. These antibodies prevent the degradation of low density lipoprotein receptor, thus lowering serum levels of LDL-cholesterol and potently reducing serum cholesterol in mice, and selectively reduce LDL-cholesterol in cynomolgus monkeys. In order to increase the pharmacokinetic and efficacy of this promising therapeutic for hypercholesterolemia, we engineered pH-sensitive binding to mouse, cynomolgus, and human PCSK9 into J16, resulting in J17. This antibody shows prolonged half-life and increased duration of cholesterol lowering in two species in vivo by binding to endogenous PCSK9 in mice and cynomolgus monkeys, respectively. The proposed mechanism of this pH-sensitive antibody is that it binds with high affinity to PCSK9 in the plasma at pH 7.4, whereas the antibody antigen complex dissociates at the endosomal pH of 5.5-6.0 in order to escape from target-mediated degradation. Additionally, this enables the antibody to bind to another PCSK9 and therefore increase the antigen-binding cycles. Furthermore, we show that this effect is dependent on the neonatal Fc receptor, which rescues the dissociated antibody in the endosome from degradation. Engineered pH sensitive antibodies may enable less frequent or lower dosing of antibodies hampered by target-mediated clearance and high antigen load. PMID- 22294693 TI - Structural and functional characterization of Bc28.1, major erythrocyte-binding protein from Babesia canis merozoite surface. AB - Babesiosis (formerly known as piroplasmosis) is a tick-borne disease caused by the intraerythrocytic development of protozoa parasites from the genus Babesia. Like Plasmodium falciparum, the agent of malaria, or Toxoplasma gondii, responsible for human toxoplasmosis, Babesia belongs to the Apicomplexa family. Babesia canis is the agent of the canine babesiosis in Europe. Clinical manifestations of this disease range from mild to severe and possibly lead to death by multiple organ failure. The identification and characterization of parasite surface proteins represent major goals, both for the understanding of the Apicomplexa invasion process and for the vaccine potential of such antigens. Indeed, we have already shown that Bd37, the major antigenic adhesion protein from Babesia divergens, the agent of bovine babesiosis, was able to induce complete protection against various parasite strains. The major merozoite surface antigens of Babesia canis have been described as a 28-kDa membrane protein family, anchored at the surface of the merozoite. Here, we demonstrate that Bc28.1, a major member of this multigenic family, is expressed at high levels at the surface of the merozoite. This protein is also found in the parasite in vitro culture supernatants, which are the basis of effective vaccines against canine babesiosis. We defined the erythrocyte binding function of Bc28.1 and determined its high resolution solution structure using NMR spectroscopy. Surprisingly, although these proteins are thought to play a similar role in the adhesion process, the structure of Bc28.1 from B. canis appears unrelated to the previously published structure of Bd37 from B. divergens. Site-directed mutagenesis experiments also suggest that the mechanism of the interaction with the erythrocyte membrane could be different for the two proteins. The resolution of the structure of Bc28 represents a milestone for the characterization of the parasite erythrocyte binding and its interaction with the host immune system. PMID- 22294694 TI - Crystal structure of novel metallocarboxypeptidase inhibitor from marine mollusk Nerita versicolor in complex with human carboxypeptidase A4. AB - NvCI is a novel exogenous proteinaceous inhibitor of metallocarboxypeptidases from the marine snail Nerita versicolor. The complex between human carboxypeptidase A4 and NvCI has been crystallized and determined at 1.7 A resolution. The NvCI structure defines a distinctive protein fold basically composed of a two-stranded antiparallel beta-sheet connected by three loops and the inhibitory C-terminal tail and stabilized by three disulfide bridges. NvCI is a tight-binding inhibitor that interacts with the active site of the enzyme in a substrate-like manner. NvCI displays an extended and novel interface with human carboxypeptidase A4, responsible for inhibitory constants in the picomolar range for some members of the M14A subfamily of carboxypeptidases. This makes NvCI the strongest inhibitor reported so far for this family. The structural homology displayed by the C-terminal tails of different carboxypeptidase inhibitors represents a relevant example of convergent evolution. PMID- 22294695 TI - Human primary keratinocytes show restricted ability to up-regulate suppressor of cytokine signaling (SOCS)3 protein compared with autologous macrophages. AB - Suppressor of cytokine signaling (SOCS)3 belongs to a family of proteins that are known to exert important functions as inducible feedback inhibitors and are crucial for the balance of immune responses. There is evidence for a deregulated immune response in chronic inflammatory skin diseases. Thus, it was the aim of this study to investigate the regulation of SOCS proteins involved in intracellular signaling pathways occurring during inflammatory skin diseases and analyze their impact on the course of inflammatory responses. Because we and others have previously described that the cytokine IL-27 has an important impact on the chronic manifestation of inflammatory skin diseases, we focused here on the signaling induced by IL-27 in human primary keratinocytes compared with autologous blood-derived macrophages. Here, we demonstrate that SOCS3 is critically involved in regulating the cell-specific response to IL-27. SOCS3 was found to be significantly up-regulated by IL-27 in macrophages but not in keratinocytes. Other STAT3-activating cytokines investigated, including IL-6, IL 22, and oncostatin M, also failed to up-regulate SOCS3 in keratinocytes. Lack of SOCS3 up-regulation in skin epithelial cells was accompanied by prolonged STAT1 and STAT3 phosphorylation and enhanced CXCL10 production upon IL-27 stimulation compared with macrophages. Overexpression of SOCS3 in keratinocytes significantly diminished this enhanced CXCL10 production in response to IL-27. We conclude from our data that keratinocytes have a cell type-specific impaired capacity to up regulate SOCS3 which may crucially determine the course of chronic inflammatory skin diseases. PMID- 22294696 TI - Interleukin-22 is produced by invariant natural killer T lymphocytes during influenza A virus infection: potential role in protection against lung epithelial damages. AB - Invariant natural killer T (iNKT) cells are non-conventional lipid-reactive alphabeta T lymphocytes that play a key role in host responses during viral infections, in particular through the swift production of cytokines. Their beneficial role during experimental influenza A virus (IAV) infection has recently been proposed, although the mechanisms involved remain elusive. Here we show that during in vivo IAV infection, mouse pulmonary iNKT cells produce IFN gamma and IL-22, a Th17-related cytokine critical in mucosal immunity. Although permissive to viral replication, IL-22 production by iNKT cells is not due to IAV infection per se of these cells but is indirectly mediated by IAV-infected dendritic cells (DCs). We show that activation of the viral RNA sensors TLR7 and RIG-I in DCs is important for triggering IL-22 secretion by iNKT cells, whereas the NOD-like receptors NOD2 and NLRP3 are dispensable. Invariant NKT cells respond to IL-1beta and IL-23 provided by infected DCs independently of the CD1d molecule to release IL-22. In vitro, IL-22 protects IAV-infected airway epithelial cells against mortality but has no role on viral replication. Finally, during early IAV infection, IL-22 plays a positive role in the control of lung epithelial damages. Overall, IAV infection of DCs activates iNKT cells, providing a rapid source of IL-22 that might be beneficial to preserve the lung epithelium integrity. PMID- 22294697 TI - ATP-dependent mitochondrial porphyrin importer ABCB6 protects against phenylhydrazine toxicity. AB - Abcb6 is a mammalian mitochondrial ATP-binding cassette (ABC) transporter that regulates de novo porphyrin synthesis. In previous studies, haploinsufficient (Abcb6(+/-)) embryonic stem cells showed impaired porphyrin synthesis. Unexpectedly, Abcb6(-/-) mice derived from these stem cells appeared phenotypically normal. We hypothesized that other ATP-dependent and/or independent mechanisms conserve porphyrins. Here, we demonstrate that Abcb6(-/-) mice lack mitochondrial ATP-driven import of coproporphyrin III. Gene expression analysis revealed that loss of Abcb6 results in up-regulation of compensatory porphyrin and iron pathways, associated with elevated protoporphyrin IX (PPIX). Phenylhydrazine-induced stress caused higher mortality in Abcb6(-/-) mice, possibly because of sustained elevation of PPIX and an inability to convert PPIX to heme despite elevated ferrochelatase levels. Therefore, Abcb6 is the sole ATP dependent porphyrin importer, and loss of Abcb6 produces up-regulation of heme and iron pathways necessary for normal development. However, under extreme demand for porphyrins (e.g. phenylhydrazine stress), these adaptations appear inadequate, which suggests that under these conditions Abcb6 is important for optimal survival. PMID- 22294698 TI - Lipid polarity is maintained in absence of tight junctions. AB - The role of tight junctions (TJs) in the establishment and maintenance of lipid polarity in epithelial cells has long been a subject of controversy. We have addressed this issue using lysenin, a toxin derived from earthworms, and an influenza virus labeled with a fluorescent lipid, octadecylrhodamine B (R18). When epithelial cells are stained with lysenin, lysenin selectively binds to their apical membranes. Using an artificial liposome, we demonstrated that lysenin recognizes the membrane domains where sphingomyelins are clustered. Interestingly, lysenin selectively stained the apical membranes of epithelial cells depleted of zonula occludens proteins (ZO-deficient cells), which completely lack TJs. Furthermore, the fluorescent lipid inserted into the apical membrane by fusion with the influenza virus did not diffuse to the lateral membrane in ZO-deficient epithelial cells. This study revealed that sphingomyelin cluster formation occurs only in the apical membrane and that lipid polarity is maintained even in the absence of TJs. PMID- 22294699 TI - Identification and characterization of nardilysin as a novel dimethyl H3K4 binding protein involved in transcriptional regulation. AB - Histone methylation on lysine residues is believed to function primarily as docking sites to recruit specific proteins termed as histone code "readers" or "effectors." Each lysine residue can be mono-, di, and tri-methylated and different methylation states can have different effect on chromatin function. While an increasing number of proteins have been identified and characterized as specific effectors for methylated histones, very few of the proteins are known to recognize a particular state of methylation. In this study, we identified nardilysin (NRDc), a member of M16 family metalloendopeptidases, as a novel dimethyl-H3K4 (H3K4me2)-binding protein. Among three methylated states, NRDc binds preferentially H3K4me2 both in vitro and in vivo. Biochemical purification demonstrated that NRDc interacts with the NCoR/SMRT corepressor complex. We identified target genes repressed by NRDc through microarray. We showed that NRDc is physically associated with and recruits the NCoR complex to some of the repressed genes and this association correlates with binding of H3K4me2. Thus, our study has identified a novel H3K4me2-binding protein and revealed a role of NRDc in transcriptional regulation. PMID- 22294700 TI - Internalization of proprotein convertase PC7 from plasma membrane is mediated by a novel motif. AB - Proprotein convertase 7 (PC7) is a member of the subtilisin-like proprotein convertase family, which is involved in the endoproteolysis of a variety of precursor proteins. Under steady state conditions, PC7 is mainly localized in the trans-Golgi network, but a small fraction is found at the cell surface. So far, no sorting signals for membrane trafficking have been identified in PC7. In this study, we have examined the internalization of PC7 from the plasma membrane. Our results show that internalization of PC7 is mediated by clathrin-coated vesicles. After inhibition of clathrin-mediated endocytosis using hypertonic conditions or the small molecule inhibitor, Pitstop 2, PC7 accumulated at the plasma membrane. Furthermore, PC7 was present in isolated clathrin-coated vesicles. To determine the internalization motif, constructs were generated in which parts of the N and C terminus of the cytoplasmic tail of PC7 were deleted, and chimeric proteins were constructed consisting of the luminal and transmembrane domains of Tac (CD25) and parts of the cytoplasmic domain of PC7. Antibody uptake experiments as well as surface biotinylation experiments demonstrated that the region between Ala(713) and Cys(726) in the cytoplasmic domain of PC7 is essential and sufficient for the internalization of PC7 but not for trans-Golgi network localization. Individual amino acids in this region were substituted with alanine, which identified Pro, Leu, and Cys as the essential amino acids. In conclusion, internalization of PC7 depends on a short transferable sequence in the cytoplasmic tail, which contains the three crucial amino acids PLC. PMID- 22294701 TI - Adjusted subpixel method enables optimisation of bronchial measurements in high resolution CT. AB - OBJECTIVES: The purpose of this paper is to present a new technique of high resolution computed tomography (HRCT) bronchial measurement, which was worked out in our centre and is based on a mathematically adjusted subpixel method (ASM). METHODS: This study used a bronchial tree model comprising two polyvinyl chloride/rubber pipes with various densities placed in a larger plastic object. External and internal diameters of both pipes corresponded to the sizes of structures that are usually evaluated in HRCT scans (i.e. the bronchus with accompanying blood vessel). The model was subjected to repeated HRCT measurements of the external and internal diameters of model pipes using a subpixel technique and ASM. RESULTS: Significant differences were observed between mean values of external and internal diameters of model pipes determined by means of subpixel method or ASM, with the latter being the ones that resembled real diameters of the model pipes more closely. Mean external diameters of the larger and smaller model pipes determined by ASM differed from the real diameters by 0.23% and 0.57%, respectively. The internal diameter of the larger pipe was on average 25.96% larger, whereas the internal diameter of the smaller pipe was 48.05% smaller than the real diameter. CONCLUSION: The technique of non-linear prediction of HRCT bronchial measurements described in this paper raises attractive prospects in its clinical application owing to potential improvements in the objectivity and reproducibility of bronchial wall measurements. PMID- 22294703 TI - Signal-to-noise ratio increase in carotid atheroma MRI: a comparison of 1.5 and 3 T. AB - OBJECTIVES: This study reports quantitative comparisons of signal-to-noise ratio (SNR) at 1.5 and 3 T from images of carotid atheroma obtained using a multicontrast, cardiac-gated, blood-suppressed fast spin echo protocol. METHODS: 18 subjects, with carotid atherosclerosis (>30% stenosis) confirmed on ultrasound, were imaged on both 1.5 and 3 T systems using phased-array coils with matched hardware specifications. T(1) weighted (T(1)W), T(2) weighted (T(2)W) and proton density-weighted (PDW) images were acquired with identical scan times. Multiple slices were prescribed to encompass both the carotid bifurcation and the plaque. Image quality was quantified using the SNR and contrast-to-noise ratio (CNR). A phantom experiment was also performed to validate the SNR method and confirm the size of the improvement in SNR. Comparisons of the SNR values from the vessel wall with muscle and plaque/lumen CNR measurements were performed at a patient level. To account for the multiple comparisons a Bonferroni correction was applied. RESULTS: One subject was excluded from the protocol owing to image quality and protocol failure. The mean improvement in SNR in plaque was 1.9, 2.1 and 2.1 in T(1)W, T(2)W and PDW images, respectively. All plaque SNR improvements were statistically significant at the p<0.05 level. The phantom experiment reported an improvement in SNR of 2.4 for PDW images. CONCLUSIONS: Significant gains in SNR can be obtained for carotid atheroma imaging at 3 T compared with 1.5 T. There was also a trend towards increased CNR. However, this was not significant after the application of the Bonferroni correction. PMID- 22294702 TI - Radiation damage and radioprotectants: new concepts in the era of molecular medicine. AB - Exposure to ionising radiation results in mutagenesis and cell death, and the clinical manifestations depend on the dose and the involved body area. Reducing carcinogenesis in patients treated with radiotherapy, exposed to diagnostic radiation or who are in certain professional groups is mandatory. The prevention or treatment of early and late radiotherapy effects would improve quality of life and increase cancer curability by intensifying therapies. Experimental and clinical data have given rise to new concepts and a large pool of chemical and molecular agents that could be effective in the protection and treatment of radiation damage. To date, amifostine is the only drug recommended as an effective radioprotectant. This review identifies five distinct types of radiation damage (I, cellular depletion; II, reactive gene activation; III, tissue disorganisation; IV, stochastic effects; V, bystander effects) and classifies the radioprotective agents into five relevant categories (A, protectants against all types of radiation effects; B, death pathway modulators; C, blockers of inflammation, chemotaxis and autocrine/paracrine pathways; D, antimutagenic keepers of genomic integrity; E, agents that block bystander effects). The necessity of establishing and funding central committees that guide systematic clinical research into evaluating the novel agents revealed in the era of molecular medicine is stressed. PMID- 22294704 TI - Quality assurance analysis of participating centres' protocol compliance to a UK multicentre hypofractionated breast (FAST) trial. AB - OBJECTIVES: The FAST (FASTer radiotherapy for breast radiotherapy) trial is a UK Phase 2 multicentre randomised clinical trial evaluating a five-fraction schedule of whole-breast radiotherapy following local excision of early breast cancer. The purpose of this quality assurance study was to analyse the radiotherapy planning data in order to confirm compliance with the trial protocol. METHODS: 915 patients were recruited between 2004 and 2007 from 18 centres. The protocol required that all centres should use three-dimensional dose compensations to optimise radiotherapy plans. Planning techniques, maximum dose (D(max)) and dose volume histograms from treatment plans were evaluated and compared between centres. The homogeneity of plans was tested by creating a cut-off value of 5% for the percentage of breast volume receiving >105% of the prescribed dose. RESULTS: 672 data sets from 15 centres were available. 93% (624/672) of plans were treated using forward-planned multileaf collimator (MLC) segments, 6% with breast compensators and 1% with inverse-planned MLC segments. 94% (635/672) of patients had a D(max)<=107% of the prescribed dose. 11% (74/672) of plans delivered >105% of the prescribed dose to >5% of the breast volume. CONCLUSION: Reviewing the data in this study, 95% of plans submitted by centres complied with the protocol. With the improved breast radiotherapy standards shown in FAST centres, the following recommendations were suggested for future UK breast radiotherapy trials: (i) the minimum, mean and maximum dose to the whole-breast planning target volume (PTV) should be recorded and assessed; (ii) apart from having a D(max)<=107% of the prescribed dose, <=5% of PTV should a receive dose >105% of the prescription dose. PMID- 22294705 TI - Detection of residual brain arteriovenous malformations after radiosurgery: diagnostic accuracy of contrast-enhanced four-dimensional MR angiography at 3.0 T. AB - OBJECTIVE: To evaluate the diagnostic accuracy of four-dimensional MR angiography (4D-MRA) at 3.0 T for detecting residual arteriovenous malformations (AVMs) after Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) radiosurgery (GKRS). METHODS: We assessed 36 angiographically confirmed AVMs in 36 patients who had been treated with GKRS. 4D-MRA was performed after GKRS and the time intervals were 39.4 +/- 26.0 months [mean +/- standard deviation (SD)]. 4D-MRA was obtained at 3.0 T after contrast injection, with a measured voxel size of 1 * 1 * 1 mm and a temporal resolution of 1.1 s (13 patients) or a voxel size of 1 * 1 * 2 mm and a temporal resolution of 0.98 s (23 patients). X-ray angiography was performed as the standard reference within 53 +/- 47 days (mean +/- SD) after MRA. To determine a residual AVM, the 4D-MRA results were independently reviewed by two readers blinded to the X-ray angiography results. We evaluated diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 4D-MRA for detection of a residual AVM. RESULTS: A residual AVM was identified in 13 patients (13/36, 36%) on X-ray angiography. According to Readers 1 and 2, 4D-MRA had a sensitivity of 79.6% and 64.3%, a specificity of 90.9% and 100%, a PPV of 84.6% and 100% and an NPV of 90% and 81.5%, respectively, and a diagnostic accuracy of 86.1% for Readers 1 and 2, for detecting residual AVMs after GKRS. CONCLUSION: The diagnostic accuracy of 4D-MRA at 3.0 T seems high, but there is still the possibility of further improving the spatiotemporal resolution of this technique. PMID- 22294706 TI - Quality measurement and improvement in the cardiac catheterization laboratory. PMID- 22294708 TI - Personalized cardiovascular medicine and drug development: time for a new paradigm. PMID- 22294709 TI - Electrical heart activity recorded during prolonged avalanche burial. PMID- 22294707 TI - Epidemiology and genetics of sudden cardiac death. PMID- 22294710 TI - Spontaneous Fontan physiology in burnt-out endomyocardial fibrosis. PMID- 22294712 TI - Letter by Lecoultre and Tam regarding article, "Increased adipose tissue oxygen tension in obese compared with lean men is accompanied by insulin resistance, impaired adipose tissue capillarization, and inflammation". PMID- 22294713 TI - Letter by Karam and Marijon regarding article, "Atrial fibrillation: outpatient presentation and management". PMID- 22294714 TI - Letter by Montone et al regarding article, "Atrial fibrillation: outpatient presentation and management". PMID- 22294715 TI - Letter by Madias regarding the article, "Repolarization alternans reveals vulnerability to human atrial fibrillation". PMID- 22294716 TI - The value of triple antibody (34betaE12 + p63 + AMACR) cocktail stain in radical prostatectomy specimens with crushed surgical margins. AB - BACKGROUND: Triple antibody cocktail immunohistochemical staining is routinely used as an ancillary method to establish a diagnosis of prostate cancer in biopsies with small foci of atypical glands. Crush artefact can distort surgical margins in radical prostatectomy specimens, occasionally making it difficult to diagnose a positive margin. AIM: To investigate the ability of a cocktail stain to distinguish carcinoma from benign prostatic glands at the edge of crushed margins in prostatectomy specimens. METHODS: 10 radical prostatectomy specimens with crushed benign glands at the surgical margins, and 20 with crushed margins positive for carcinoma were retrieved from the pathology archives. The latter included 16 (80%) with positive apical margins, 2 (10%) incised intraprostatic margins, and 1 (5%) soft tissue margin. Two-colour triple antibody stain using a cocktail of antibodies against alpha-methylacyl coenzyme A racemase (AMACR), high molecular weight keratin and p63 was performed on all the selected cases. RESULTS: In 10/10 specimens with crushed benign glands, basal cell staining continued to be detectable, while AMACR staining was negative in all cases (0/10). In the positive margin cases, none of the crushed glands expressed basal cell marker staining (0/20), whereas 14/20 (70%) of the cases showed variable levels of AMACR positivity at the inked margin. CONCLUSION: Two-colour triple antibody cocktail stain is useful in the assessment of most, but not all, surgical margins with crushed artefact in prostatectomy specimens by helping to establish whether glands are malignant or benign. PMID- 22294717 TI - Application of the UK NHS Improvement Anticoagulation Commissioning Support Document for 'safety indicators' in atrial fibrillation. Results of the European Action on Anticoagulation study. AB - INTRODUCTION: 'Safety indicators' in the anticoagulant management of atrial fibrillation (AF) are listed in the UK NHS Improvement Document, 'Anticoagulation for AF', aiming to promote quality services. Acceptable clinical event rates are not quantified in the document. OBJECTIVE: To provide clinical evaluation of the relevant safety indicators using data from a recent large European Action on Anticoagulation (EAA) study. RESULTS: 469 clinical events were recorded in 5839 outpatients in the EAA study. The safety indicators listed in the NHS Improvement Document were related to these patients with AF. The relevance of the 'safety indicators' is confirmed by the EAA study for patients starting oral anticoagulation and for those already receiving oral anticoagulation, and quantified. CONCLUSION: The EAA clinical study provides a quantitative basis for the safety indicators' in AF listed in the NHS Commissioning Support Document and emphasises the importance of the document. PMID- 22294718 TI - Preclinical pharmacology of AZD5363, an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of monotherapy activity with genetic background. AB - AKT is a key node in the most frequently deregulated signaling network in human cancer. AZD5363, a novel pyrrolopyrimidine-derived compound, inhibited all AKT isoforms with a potency of 10 nmol/L or less and inhibited phosphorylation of AKT substrates in cells with a potency of approximately 0.3 to 0.8 MUmol/L. AZD5363 monotherapy inhibited the proliferation of 41 of 182 solid and hematologic tumor cell lines with a potency of 3 MUmol/L or less. Cell lines derived from breast cancers showed the highest frequency of sensitivity. There was a significant relationship between the presence of PIK3CA and/or PTEN mutations and sensitivity to AZD5363 and between RAS mutations and resistance. Oral dosing of AZD5363 to nude mice caused dose- and time-dependent reduction of PRAS40, GSK3beta, and S6 phosphorylation in BT474c xenografts (PRAS40 phosphorylation EC(50) ~ 0.1 MUmol/L total plasma exposure), reversible increases in blood glucose concentrations, and dose-dependent decreases in 2[18F]fluoro-2-deoxy-D-glucose ((18)F-FDG) uptake in U87-MG xenografts. Chronic oral dosing of AZD5363 caused dose-dependent growth inhibition of xenografts derived from various tumor types, including HER2(+) breast cancer models that are resistant to trastuzumab. AZD5363 also significantly enhanced the antitumor activity of docetaxel, lapatinib, and trastuzumab in breast cancer xenografts. It is concluded that AZD5363 is a potent inhibitor of AKT with pharmacodynamic activity in vivo, has potential to treat a range of solid and hematologic tumors as monotherapy or a combinatorial agent, and has potential for personalized medicine based on the genetic status of PIK3CA, PTEN, and RAS. AZD5363 is currently in phase I clinical trials. PMID- 22294719 TI - Driving up the quality and relevance of research through the use of agreed core outcomes. PMID- 22294721 TI - Myth: C-sections are on the rise because more mothers are asking for them. PMID- 22294722 TI - Correlation between gene expression of IGF-1R pathway markers and cetuximab benefit in metastatic colorectal cancer. AB - PURPOSE: This study examined potential correlations between markers related to the insulin-like growth factor-1 receptor (IGF-1R) pathway and clinical benefit from the anti-epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in metastatic colorectal cancer (mCRC). EXPERIMENTAL DESIGN: Gene expression profiles for 70 pretreatment specimens from metastatic lesions of patients with chemorefractory mCRC receiving cetuximab monotherapy were analyzed using 74 predefined Gene-Chip probesets representing 33 unique IGF-1R pathway markers to determine correlations with progression-free survival (PFS) and disease control rate. RESULTS: Higher IGF-1R, higher GRB(7), and lower INSIG(2) expression were associated with longer PFS with cetuximab in univariate analyses, particularly in patients with wild-type K-Ras tumors: median, 122 versus 60 days (P = 0.01), 122 versus 57 days (P = 0.011), and 57 versus 156 days (P < 0.0001), favoring higher IGF-1R, higher GRB(7), and lower INSIG(2) expression, respectively. Lower IGF-1 expression was associated with a PFS benefit with cetuximab, whereas lower IGFBP(3) and INSR expression levels showed trends for a PFS benefit. Lower INSIG(2) expression (vs. higher expression) was associated with greater PFS in the high epiregulin-expressing group (P = 0.001), but not in the low-expressing cohort suggesting an effect independent from the previously reported effect of epiregulin expression. Lower INSIG(2) expression was also associated with higher disease control rate in the overall population (51.4% vs. 11.4%; P = 0.001) and wild-type K-Ras subset (76.2% vs. 18.2%; P < 0.0001). CONCLUSIONS: These results suggest that markers of the IGF-1R pathway may play a role in predicting benefit from cetuximab therapy in mCRC. Additional clinical studies are warranted to validate these findings. PMID- 22294723 TI - Mechanisms of CHD5 Inactivation in neuroblastomas. AB - PURPOSE: Neuroblastomas (NBs) have genomic, biological, and clinical heterogeneity. High-risk NBs are characterized by several genomic changes, including MYCN amplification and 1p36 deletion. We identified the chromatin remodeling gene CHD5 as a tumor suppressor gene that maps to 1p36.31. Low or absent CHD5 expression is associated with a 1p36 deletion and an unfavorable outcome, but the mechanisms of CHD5 inactivation in NBs are unknown. EXPERIMENTAL DESIGN: We examined (i) the CHD5 sequence in 188 high-risk NBs investigated through the TARGET initiative, (ii) the methylation status of the CHD5 promoter in 108 NBs with or without 1p36 deletion and/or MYCN amplification, and (iii) mRNA expression of CHD5 and MYCN in 814 representative NBs using TaqMan low density array microfluidic cards. RESULTS: We found no examples of somatically acquired CHD5 mutations, even in cases with 1p36 deletion, indicating that homozygous genomic inactivation is rare. Methylation of the CHD5 promoter was common in the high-risk tumors, and it was generally associated with both 1p deletion and MYCN amplification. High CHD5 expression was a powerful predictor of favorable outcome, and it showed prognostic value even in multivariable analysis after adjusting for MYCN amplification, 1p36 deletion, and/or 11q deletion. CONCLUSIONS: We conclude that (i) somatically acquired CHD5 mutations are rare in primary NBs, so inactivation probably occurs by deletion and epigenetic silencing; (ii) CHD5 expression and promoter methylation are associated with MYCN amplification, suggesting a possible interaction between these 2 genes; and (iii) high CHD5 expression is strongly correlated with favorable clinical/biological features and outcome. PMID- 22294724 TI - Preferences of group-housed female mice regarding structure of softwood bedding. AB - Bedding influences various parameters in the housing of laboratory mice, such as health, physiology and behaviour (often considered as being integral parts of welfare). Notwithstanding existent studies about bedding preferences of individually tested mice, data about group-housed mice are still lacking. The aim of this study was to find out the structure preference for softwood bedding of group-housed mice. One hundred and eight 8-week-old female mice (C57BL6/JOlaHsd and BALB/cOlaHsd) were housed in groups of three and were given one-week free access to two different bedding structures at a time. In three test combinations, softwood shaving bedding was tested versus softwood chip bedding products of three different particle sizes (fine/medium/coarse-grained). The preference test was performed in a DoubleCage system composed of two Makrolon type IIL cages, connected by a perspex tunnel. This validated system was able to detect the crossings of each individual animal with correct crossing time and direction. On the basis of these data, dwelling times on the particular bedding structures were statistically analysed as a parameter for bedding preferences. In all three test combinations, a highly significant shaving preference was detected. On average, mice spent 70% of their dwelling time on the shavings. This preference was more explicit during the light period and in C57BL/6J mice. The relative ranking of the bedding structures was: shavings >> coarse-grained chips > medium chips = fine chips. By means of these results, a shaving structure as bedding can be recommended for laboratory mice, whereas fine chip structures should be avoided. PMID- 22294725 TI - The influence of food restriction versus ad libitum feeding of chow and purified diets on variation in body weight, growth and physiology of female Wistar rats. AB - Ad libitum (AL) supply of standard chow is the feeding method most often used for rodents in animal experiments. However, AL feeding is known to result in a shorter lifespan and decreased health as compared with restricted feeding. Restricted feeding and thus limiting calorie intake prevents many health problems, increases lifespan and can also increase group uniformity. All this leads to a reduced number of animals needed. So-called standard chows are known to be prone to variation in composition. Synthetic foods have a more standard composition, contributing to group uniformity which, like diet reduction, may decrease the number of animals necessary to obtain statistical significance. In this study, we compared the effects of AL versus restricted feeding (25% reduction in food intake) on standard chow versus synthetic food of three different suppliers on body weight (BW), growth, several blood parameters and organ weights in growing female Wistar rats over a period of 61 days. Diet restriction led to a decreased growth and significantly reduced variation in BW and growth as compared with AL feeding. AL feeding on synthetic diets caused a significantly higher BW gain than on chow diets. Due to experimental design, this same effect occurred on food restriction. Blood parameters and organ weights were affected neither by diet type nor by amount. Incidentally, variations were significantly reduced on food restriction versus AL, and on synthetic diets versus chow diets. This study demonstrates that food restriction versus AL feeding leads to a significantly reduced variation in BW and growth, thereby indicating the potential for reduction when applying this feeding schedule. PMID- 22294726 TI - Calcium blockers decrease the bortezomib resistance in mantle cell lymphoma via manipulation of tissue transglutaminase activities. AB - Although bortezomib is clinically approved for the treatment of mantle cell lymphoma (MCL), only limited effects of this treatment have been demonstrated. To improve survival for bortezomib-resistant patients, it is necessary to develop new therapeutic strategies. In the present study, we used biochemical and molecular methodologies to demonstrate that tissue transglutaminase (TG) activates downstream NF-kappaB signaling pathways. The signaling axis from TG to NF-kappaB could be a new therapeutic target to overcome bortezomib resistance in MCL. TG2 is a calcium-dependent protein cross-linking enzyme reported to be overexpressed in various cancer cells. We found that MCL cells expressed elevated levels of TG2 and that the modification of TG2 activities altered NF-kappaB expression and downstream signaling in MCL cells. When TG2 signaling was inhibited by calcium blockers, the combination of a calcium blocker (perillyl alcohol) with bortezomib suppressed NF-kappaB expression and improved the cytotoxicity of bortezomib in MCL cells. Our study is the first to show the expression of TG2 and the contribution of TG2 to NF-kappaB signaling in MCL. TG2 inhibition may be used as an alternative target anti-MCL therapy, and calcium blockers may be combined with bortezomib to overcome the bortezomib resistance in MCL. PMID- 22294727 TI - In vivo effects of eltrombopag on platelet function in immune thrombocytopenia: no evidence of platelet activation. AB - The effects of eltrombopag, a thrombopoietin-receptor agonist, on platelet function in immune thrombocytopenia (ITP) are not fully characterized. This study used whole blood flow cytometry to examine platelet function in 20 patients receiving eltrombopag treatment at days 0, 7, and 28. Platelet surface expression of activated GPIIb/IIIa, P-selectin, and GPIb was measured with and without low and high adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP) concentrations. Before eltrombopag treatment with no ex vivo agonist, platelet activation was higher in ITP patients than controls. Platelet GPIb and activated GPIIb/IIIa expression without added agonist was unchanged following eltrombopag treatment, whereas a slight increase in P-selectin was observed. Expression of P-selectin and activated GPIIb/IIIa in response to high-dose ADP was lower during eltrombopag treatment than at baseline. Eltrombopag led to a slight increase in platelet reactivity to TRAP only in responders to eltrombopag but not to levels above those in controls; whole blood experiments demonstrated that this increase was probably because of higher platelet counts rather than higher platelet reactivity. In conclusion, although thrombocytopenic ITP patients have higher baseline platelet activation than controls, eltrombopag did not cause platelet activation or hyper-reactivity, irrespective of whether the platelet count increased. PMID- 22294728 TI - Identification of TRIB1 R107L gain-of-function mutation in human acute megakaryocytic leukemia. AB - Trib1 has been identified as a myeloid oncogene in a murine leukemia model. Here we identified a TRIB1 somatic mutation in a human case of Down syndrome-related acute megakaryocytic leukemia. The mutation was observed at well-conserved arginine 107 residue in the pseudokinase domain. This R107L mutation remained in leukocytes of the remission stage in which GATA1 mutation disappeared, suggesting the TRIB1 mutation is an earlier genetic event in leukemogenesis. The bone marrow transfer experiment showed that acute myeloid leukemia development was accelerated by transducing murine bone marrow cells with the R107L mutant in which enhancement of ERK phosphorylation and C/EBPalpha degradation by Trib1 expression was even greater than in those expressing wild-type. These results suggest that TRIB1 may be a novel important oncogene for Down syndrome-related acute megakaryocytic leukemia. PMID- 22294729 TI - Caspase-9 mediates the apoptotic death of megakaryocytes and platelets, but is dispensable for their generation and function. AB - Apoptotic caspases, including caspase-9, are thought to facilitate platelet shedding by megakaryocytes. They are known to be activated during platelet apoptosis, and have also been implicated in platelet hemostatic responses. However, the precise requirement for, and the regulation of, apoptotic caspases have never been defined in either megakaryocytes or platelets. To establish the role of caspases in platelet production and function, we generated mice lacking caspase-9 in their hematopoietic system. We demonstrate that both megakaryocytes and platelets possess a functional apoptotic caspase cascade downstream of Bcl-2 family-mediated mitochondrial damage. Caspase-9 is the initiator caspase, and its loss blocks effector caspase activation. Surprisingly, steady-state thrombopoiesis is unperturbed in the absence of caspase-9, indicating that the apoptotic caspase cascade is not required for platelet production. In platelets, loss of caspase-9 confers resistance to the BH3 mimetic ABT-737, blocking phosphatidylserine (PS) exposure and delaying ABT-737-induced thrombocytopenia in vivo. Despite this, steady-state platelet lifespan is normal. Casp9(-/-) platelets are fully capable of physiologic hemostatic responses and functional regulation of adhesive integrins in response to agonist. These studies demonstrate that the apoptotic caspase cascade is required for the efficient death of megakaryocytes and platelets, but is dispensable for their generation and function. PMID- 22294730 TI - Oligodeoxynucleotides stabilize Helios-expressing Foxp3+ human T regulatory cells during in vitro expansion. AB - Foxp3(+) regulatory T cells (Tregs) maintain self-tolerance and adoptive therapy, and using Foxp3(+) Tregs has been proposed as treatment for autoimmune diseases. The clinical use of Tregs will require large numbers of cells and methods for in vitro expansion of Tregs are being developed. Foxp3(+) Tregs can be divided into 2 subpopulations based on expression of the transcription factor, Helios. Foxp3(+)Helios(+) Tregs (70%) are thymic-derived, whereas Foxp3(+)Helios(-) Tregs (30%) are induced in the periphery. Foxp3(+)Helios(+) Tregs differ from Foxp3(+)Helios(-) Tregs in terms of epigenetic changes at the Foxp3 locus, their capacity to produce effector cytokines, and their stability of Foxp3 expression on days to weeks of expansion in vitro. Addition of a 25 mer DNA oligonucleotide of random composition for a short period during the expansion of Foxp3(+) Tregs in vitro results in prolonged stabilization of the Foxp3(+)Helios(+) subpopulation and yields an optimal population for use in cellular biotherapy. PMID- 22294731 TI - A prospective evaluation of degranulation assays in the rapid diagnosis of familial hemophagocytic syndromes. AB - Familial hemophagocytic lymphohistiocytosis (FHL) is a life-threatening disorder of immune regulation caused by defects in lymphocyte cytotoxicity. Rapid differentiation of primary, genetic forms from secondary forms of hemophagocytic lymphohistiocytosis (HLH) is crucial for treatment decisions. We prospectively evaluated the performance of degranulation assays based on surface up-regulation of CD107a on natural killer (NK) cells and cytotoxic T lymphocytes in a cohort of 494 patients referred for evaluation for suspected HLH. Seventy-five of 77 patients (97%) with FHL3-5 and 11 of 13 patients (85%) with Griscelli syndrome type 2 or Chediak-Higashi syndrome had abnormal resting NK-cell degranulation. In contrast, NK-cell degranulation was normal in 14 of 16 patients (88%) with X linked lymphoproliferative disease and in 8 of 14 patients (57%) with FHL2, who were identified by diminished intracellular SLAM-associated protein (SAP), X linked inhibitor of apoptosis protein (XIAP), and perforin expression, respectively. Among 66 patients with a clinical diagnosis of secondary HLH, 13 of 59 (22%) had abnormal resting NK-cell degranulation, whereas 0 of 43 had abnormal degranulation using IL-2-activated NK cells. Active disease or immunosuppressive therapy did not impair the assay performance. Overall, resting NK-cell degranulation below 5% provided a 96% sensitivity for a genetic degranulation disorder and a specificity of 88%. Therefore, degranulation assays allow a rapid and reliable classification of patients, benefiting treatment decisions. PMID- 22294733 TI - Microfluidic amplification as a tool for massive parallel sequencing of the familial hypercholesterolemia genes. AB - BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disorder that affects cholesterol metabolism and is an important risk factor for heart disease. Three different genes were causally linked to this disorder: LDLR (low density lipoprotein receptor), APOB [apolipoprotein B (including Ag(x) antigen)], and PCSK9 (proprotein convertase subtilisin/kexin type 9). We evaluated a new amplicon preparation tool for resequencing these genes on next generation sequencing (NGS) platforms. METHODS: For the 3 genes, 38 primer pairs were designed and loaded on the Fluidigm Access Array, a microfluidic array in which a PCR was performed. We amplified 144 DNA samples (73 positive controls and 71 patient samples) and performed 3 sequencing runs on a GS FLX Titanium system from Roche 454, using pyrosequencing. Data were analyzed with the SeqNext module of the Sequence Pilot software. RESULT: From the 38 amplicons, 37 were amplified successfully, without any further optimization. Sequencing resulted in a mean coverage of the individual amplicons of 71-fold, 74-fold, and 117-fold for the 3 runs, respectively. In the positive controls, all known mutations were identified. In 29% of the patient samples, a pathogenic point mutation or small deletion/insertion was found. Large rearrangements were not detectable with NGS, but were picked up by multiplex ligation-dependent probe amplification. CONCLUSIONS: Combining a microfluidic amplification system with massive parallel sequencing is an effective method for mutation scanning in FH patients, which can be implemented in diagnostics. For data analysis, we propose a minimum variant frequency threshold of 20% and a minimum coverage of 25-fold. PMID- 22294732 TI - The phenotype of human STK4 deficiency. AB - We describe a novel clinical phenotype associating T- and B-cell lymphopenia, intermittent neutropenia, and atrial septal defects in 3 members of a consanguineous kindred. Their clinical histories included recurrent bacterial infections, viral infections, mucocutaneous candidiasis, cutaneous warts, and skin abscesses. Homozygosity mapping and candidate gene sequencing revealed a homozygous premature termination mutation in the gene STK4 (serine threonine kinase 4, formerly having the symbol MST1). STK4 is the human ortholog of Drosophila Hippo, the central constituent of a highly conserved pathway controlling cell growth and apoptosis. STK4-deficient lymphocytes and neutrophils exhibit enhanced loss of mitochondrial membrane potential and increased susceptibility to apoptosis. STK4 deficiency is a novel human primary immunodeficiency syndrome. PMID- 22294734 TI - Butyrylcholinesterase activity predicts long-term survival in patients with coronary artery disease. AB - BACKGROUND: Low serum butyrylcholinesterase activity was associated with all cause and cardiovascular mortality in a community-based study; however, there are no data from investigations of the long-term effects of butyrylcholinesterase on mortality in patients with diagnosed coronary artery disease (CAD). We therefore assessed the effect of butyrylcholinesterase activity on the outcomes of patients with CAD. METHODS AND RESULTS: We prospectively included 720 patients in our study: 293 patients with stable CAD and 427 patients with acute coronary syndrome. During a median follow-up of 11.3 years corresponding to 6469 overall person-years, 278 deaths (38.6%) were recorded. We detected a significant and independent protective effect of butyrylcholinesterase on all-cause mortality [adjusted hazard ratio (HR) for a 1-SD increase, 0.62; 95% CI, 0.54-0.71; P < 0.001] and cardiovascular mortality (adjusted HR, 0.64; 95% CI, 0.54-0.76; P < 0.001) in a Cox proportional hazards regression analysis. The 10-year survival rates were 42%, 74%, and 87% in the first, second, and third tertiles of butyrylcholinesterase activity. The presentation of CAD affected the effect of butyrylcholinesterase on mortality (P for interaction = 0.012), with a stronger association found in patients with stable CAD (adjusted HR, 0.56; 95% CI, 0.45 0.70; P < 0.001). CONCLUSIONS: Our study demonstrates a strong inverse association between butyrylcholinesterase activity and long-term outcome in patients with known CAD. Because butyrylcholinesterase added predictive information after adjustment for established cardiovascular risk factors, additional underlying pathophysiological mechanisms and the potential applicability of butyrylcholinesterase activity for secondary risk prediction needs to be addressed in future studies. PMID- 22294735 TI - NR4A2: effects of an "orphan" receptor on sustained attention in a schizophrenic population. AB - NR4A2 (nuclear receptor subfamily 4 group A member 2) or Nurr1 is a transcription factor implied in the differentiation, maturation, and survival of dopaminergic neurons. It also has a role in the expression of several proteins that are necessary for the synthesis and regulation of dopamine (DA), such as tyrosine hidroxilase, dopamine transporter, vesicular monoamine transporter 2, and cRET. DA is an important neurotransmitter in attentional pathways. Our aim was to evaluate the influence of NR4A2 gene in the performance of schizophrenia (SZ) patients and healthy subjects on a sustained attention task. For this study, we collected 188 SZ subjects (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and 100 control individuals. We genotyped 5 tag SNPs in NR4A2 gene: rs1150143 (C/G), rs1150144 (A/G), rs834830 (A/G), rs1466408 (T/A), and rs707132 (A/G). We also analyzed the influence of its haplotypes (frequency>5%). To examine sustained attention, all the individuals completed the Degraded Stimulus Continuous Performance Test. We evaluated "hits," "reaction time," "sensibility a," and "false alarms." In the schizophrenic group, recessive genotypes of rs1150143, rs1150144, rs834830, and rs707132 were associated with a worse performance. SZ subjects who carried GGGTG haplotype showed less hits (P<.004), lower sensibility a scores (P<.009), and a higher reaction time (P=.013). We observed a sex effect of the gene: genotype and haplotype associations were only present in the male group. We conclude that NR4A2 gene is involved in attentional deficits of SZ patients, modifying hits, sensibility a, and reaction time. PMID- 22294736 TI - Public health and biosecurity. Adaptations of avian flu virus are a cause for concern. PMID- 22294737 TI - Effect of n-3 long chain polyunsaturated fatty acid supplementation in pregnancy on infants' allergies in first year of life: randomised controlled trial. AB - OBJECTIVE: To determine whether dietary n-3 long chain polyunsaturated fatty acid (LCPUFA) supplementation of pregnant women with a fetus at high risk of allergic disease reduces immunoglobulin E associated eczema or food allergy at 1 year of age. DESIGN: Follow-up of infants at high hereditary risk of allergic disease in the Docosahexaenoic Acid to Optimise Mother Infant Outcome (DOMInO) randomised controlled trial. SETTING: Adelaide, South Australia. PARTICIPANTS: 706 infants at high hereditary risk of developing allergic disease whose mothers were participating in the DOMInO trial. INTERVENTIONS: The intervention group (n=368) was randomly allocated to receive fish oil capsules (providing 900 mg of n-3 LCPUFA daily) from 21 weeks' gestation until birth; the control group (n=338) received matched vegetable oil capsules without n-3 LCPUFA. MAIN OUTCOME MEASURE: Immunoglobulin E associated allergic disease (eczema or food allergy with sensitisation) at 1 year of age. RESULTS: No differences were seen in the overall percentage of infants with immunoglobulin E associated allergic disease between the n-3 LCPUFA and control groups (32/368 (9%) v 43/338 (13%); unadjusted relative risk 0.68, 95% confidence interval 0.43 to 1.05, P=0.08; adjusted relative risk 0.70, 0.45 to 1.09, P=0.12), although the percentage of infants diagnosed as having atopic eczema (that is, eczema with associated sensitisation) was lower in the n-3 LCPUFA group (26/368 (7%) v 39/338 (12%); unadjusted relative risk 0.61, 0.38 to 0.98, P=0.04; adjusted relative risk 0.64, 0.40 to 1.02, P=0.06). Fewer infants were sensitised to egg in the n-3 LCPUFA group (34/368 (9%) v 52/338 (15%); unadjusted relative risk 0.61, 0.40 to 0.91, P=0.02; adjusted relative risk 0.62, 0.41 to 0.93, P=0.02), but no difference between groups in immunoglobulin E associated food allergy was seen. CONCLUSION: n-3 LCPUFA supplementation in pregnancy did not reduce the overall incidence of immunoglobulin E associated allergies in the first year of life, although atopic eczema and egg sensitisation were lower. Longer term follow-up is needed to determine if supplementation has an effect on respiratory allergic diseases and aeroallergen sensitisation in childhood. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12610000735055 (DOMInO trial: ACTRN12605000569606). PMID- 22294738 TI - The consequences of abandoning the Health and Social Care Bill. PMID- 22294739 TI - Evaluating metrics for quality: death on the same day of elective pediatric surgery. AB - Surgical mortality is considered a benchmark for measuring quality of care. This study quantifies the incidence of death on the day of elective pediatric surgery, which generally is considered preventable and might be considered a "never" event. The authors conducted a retrospective analysis of national state inpatient databases from 1988 to 2007 that included elective pediatric surgical patients. A descriptive analysis of same-day mortality by demographics, surgical specialties, and age was performed. Of 835 880 elective pediatric surgical cases identified, 174 patients died on the day of surgery-that is, 2.1 deaths/10 000 cases. Surgical specialty mortality rates ranged from 0.06 (otolaryngology) to 17.4 (cardiothoracic surgery) deaths per 10 000 cases. Death on the day of elective pediatric surgery is rare, limiting its utility to compare performance in pediatric surgery. However, this metric may be useful at individual institutions as a case-finding tool for root-cause analysis in quality improvement efforts. PMID- 22294740 TI - Lansley's NHS "reforms". PMID- 22294741 TI - A covalently dimerized recombinant human bone morphogenetic protein-15 variant identifies bone morphogenetic protein receptor type 1B as a key cell surface receptor on ovarian granulosa cells. AB - Genetic studies have identified bone morphogenetic protein-15 (BMP15) as an essential regulator of female fertility in humans and in sheep. Oocyte-derived BMP15 is a noncovalently linked dimeric growth factor mediating its effects to ovarian somatic cells in a paracrine manner. Although receptor ectodomains capable of binding BMP15 have previously been reported, no cell surface receptor complex involved in BMP15 signaling has previously been characterized. Here we have expressed and purified recombinant human BMP15 noncovalent and covalent dimer variants. The biological effects of these BMP15 variants were assessed in cultured human granulosa-luteal cells or COV434 granulosa cell tumor cells using BMP-responsive transcriptional reporter assays and an inhibin B ELISA. Biochemical characterization of ligand-receptor interactions was performed with affinity-labeling experiments using [(125)I]iodinated BMP15 variants. Both ligand variants were shown to form homodimers and to stimulate Smad1/5/8 signaling and inhibin B production in human granulosa cells in a similar manner. [(125)I]Iodination of both ligands was achieved, but only the covalent dimer variant retained receptor binding capacity. The [(125)I]BMP15(S356C) variant bound preferentially to endogenous BMP receptor 1B (BMPR1B) and BMPR2 receptors on COV434 cells. Binding experiments in COS cells with overexpression of these receptors confirmed that the [(125)I]BMP15(S356C) variant binds to BMPR1B and BMPR2 forming the BMP15 signaling complex. The results provide the first direct evidence in any species on the identification of specific cell surface receptors for a member of the GDF9/BMP15 subfamily of oocyte growth factors. The fact that BMP15 uses preferentially BMPR1B as its type I receptor suggests an important role for the BMPR1B receptor in human female fertility. The result is well in line with the demonstration of ovarian failure in a recently reported human subject with a homozygous BMPR1B loss-of-function mutant. PMID- 22294742 TI - Preclinical characterization of a novel diphenyl benzamide selective ERalpha agonist for hormone therapy in prostate cancer. AB - Androgen deprivation therapy (ADT) is the mainstay of treatment for advanced prostate cancer. ADT improves overall and disease-free survival rates, but long term therapy is associated with severe side effects of androgen and estrogen depletion including hot flashes, weight gain, depression, and osteoporosis. Effective hormone reduction can be achieved without estrogen deficiency-related side effects by using therapy with estrogenic compounds. However, cardiovascular complications induced by estrogens coupled with the availability of LHRH agonists led to discontinuation of estrogen use for primary androgen deprivation therapy in the 1980s. New treatments for prostate cancer that improve patient outcomes without the serious estrogen deficiency-related toxicities associated with ADT using LHRH analogs are needed. Herein we describe a novel nonsteroidal selective estrogen receptor-alpha agonist designed for first-line therapy of advanced prostate cancer that in animal models induces medical castration and minimizes many of the estrogen deficiency-related side effects of ADT. The present studies show that orally administered GTx-758 reversibly suppressed testosterone to castrate levels and subsequently reduced prostate volume and circulating prostate specific antigen in relevant preclinical models without inducing hot flashes, bone loss, thrombophilia, hypercoagulation, or increasing fat mass. PMID- 22294743 TI - Rapid and widespread effects of 17beta-estradiol on intracellular signaling in the male songbird brain: a seasonal comparison. AB - Across vertebrate species, 17beta-estradiol (E(2)) acts on the brain via both genomic and nongenomic mechanisms to influence neuronal physiology and behavior. Nongenomic E(2) signaling is typically initiated by membrane-associated estrogen receptors that modulate intracellular signaling cascades, including rapid phosphorylation of ERK. Phosphorylated ERK (pERK) can, in turn, rapidly phosphorylate tyrosine hydroxylase (TH) and cAMP response element-binding protein (CREB). Recent data suggest that the rapid effects of E(2) on mouse aggressive behavior are more prominent during short photoperiods (winter) and that acute aromatase inhibition reduces songbird aggression in winter only. To date, seasonal plasticity in the rapid effects of E(2) on intracellular signaling has not been investigated. Here, we compared the effects of acute (15 min) E(2) treatment on pERK, pTH, and pCREB immunoreactivity in male song sparrows (Melospiza melodia) pretreated with the aromatase inhibitor fadrozole during the breeding and nonbreeding seasons. We examined immunoreactivity in 14 brain regions including portions of the song control system, social behavior network, and the hippocampus (Hp). In both seasons, E(2) significantly decreased pERK in nucleus taeniae of the amygdala, pTH in ventromedial hypothalamus, and pCREB in mesencephalic central gray, robust nucleus of the arcopallium, and caudomedial nidopallium. However, several effects were critically dependent upon season. E(2) decreased pERK in caudomedial nidopallium in the breeding season only and decreased pCREB in the medial preoptic nucleus in the nonbreeding season only. Remarkably, E(2) decreased pERK in Hp in the breeding season but increased pERK in Hp in the nonbreeding season. Together, these data demonstrate that E(2) has rapid effects on intracellular signaling in multiple regions of the male brain and also demonstrate that rapid effects of E(2) can be profoundly different across the seasons. PMID- 22294744 TI - Glucocorticoids enhance intestinal glucose uptake via the dimerized glucocorticoid receptor in enterocytes. AB - Glucocorticoid (GC) treatment of inflammatory disorders, such as inflammatory bowel disease, causes deranged metabolism, in part by enhanced intestinal resorption of glucose. However, the underlying molecular mechanism is poorly understood. Hence, we investigated transcriptional control of genes reported to be involved in glucose uptake in the small intestine after GC treatment and determined effects of GC on electrogenic glucose transport from transepithelial currents. GR(villinCre) mice lacking the GC receptor (GR) in enterocytes served to identify the target cell of GC treatment and the requirement of the GR itself; GR(dim) mice impaired in dimerization and DNA binding of the GR were used to determine the underlying molecular mechanism. Our findings revealed that oral administration of dexamethasone to wild-type mice for 3 d increased mRNA expression of serum- and GC-inducible kinase 1, sodium-coupled glucose transporter 1, and Na(+)/H(+) exchanger 3, as well as electrogenic glucose transport in the small intestine. In contrast, GR(villinCre) mice did not respond to GC treatment, neither with regard to gene activation nor to glucose transport. GR(dim) mice were also refractory to GC, because dexamethasone treatment failed to increase both, gene expression and electrogenic glucose transport. In addition, the rise in blood glucose levels normally observed after GC administration was attenuated in both mutant mouse strains. We conclude that enhanced glucose transport in vivo primarily depends on gene regulation by the dimerized GR in enterocytes, and that this mechanism contributes to GC-induced hyperglycemia. PMID- 22294745 TI - Impact of Oatp1c1 deficiency on thyroid hormone metabolism and action in the mouse brain. AB - Organic anion-transporting polypeptide 1c1 (Oatp1c1) (also known as Slco1c1 and Oatp14) belongs to the family of Oatp and has been shown to facilitate the transport of T(4). In the rodent brain, Oatp1c1 is highly enriched in capillary endothelial cells and choroid plexus structures where it may mediate the entry of T(4) into the central nervous system. Here, we describe the generation and first analysis of Oatp1c1-deficient mice. Oatp1c1 knockout (KO) mice were born with the expected frequency, were not growth retarded, and developed without any overt neurological abnormalities. Serum T(3) and T(4) concentrations as well as renal and hepatic deiodinase type 1 expression levels were indistinguishable between Oatp1c1 KO mice and control animals. Hypothalamic TRH and pituitary TSH mRNA levels were not affected, but brain T(4) and T(3) content was decreased in Oatp1c1-deficient animals. Moreover, increased type 2 and decreased type 3 deiodinase activities indicate a mild hypothyroid situation in the brain of Oatp1c1 KO mice. Consequently, mRNA expression levels of gene products positively regulated by T(3) in the brain were down-regulated. This central nervous system specific hypothyroidism is presumably caused by an impaired passage of T(4) across the blood-brain barrier and indicates a unique function of Oatp1c1 in facilitating T(4) transport despite the presence of other thyroid hormone transporters such as Mct8. PMID- 22294746 TI - Excess DAX1 leads to XY ovotesticular disorder of sex development (DSD) in mice by inhibiting steroidogenic factor-1 (SF1) activation of the testis enhancer of SRY-box-9 (Sox9). AB - Human DAX1 duplications cause dosage-sensitive sex reversal (DSS) whereby chromosomally XY individuals can develop as females due to gonadal dysgenesis. However, the mechanism of DSS-adrenal hypoplasia congenita on X, gene 1 (DAX1) action in the fetal testis is unknown. We show that in fetal testes from XY Dax1 overexpressing transgenic mice, the expression of the key testis-promoting gene sex-determining region on Y (SRY)-box-9 (Sox9) is reduced. Moreover, in XY Sox9 heterozygotes, in which testis development is usually normal, Dax1 overexpression results in ovotestes, suggesting a DAX1-SOX9 antagonism. The ovarian portion of the XY ovotestes was characterized by expression of the granulosa cell marker, Forkhead box-L2, with complete loss of the Sertoli cell markers, SOX9 and anti Mullerian hormone, and the Leydig cell marker CYP17A1. However, the expression of SRY and steroidogenic factor-1 (SF1), two key transcriptional regulators of Sox9, was retained in the ovarian portion of the XY ovotestes. Using reporter mice, Dax1 overexpression reduced activation of TES, the testis enhancer of Sox9, indicating that DAX1 might repress Sox9 expression via TES. In cultured cells, increasing levels of DAX1 antagonized SF1-, SF1/SRY-, and SF1/SOX9-mediated activation of TES, due to reduced binding of SF1 to TES, providing a likely mechanism for DSS. PMID- 22294747 TI - Evidence for differential regulation of GnRH signaling via heterodimerization among GnRH receptor paralogs in the protochordate, Ciona intestinalis. AB - The endocrine and neuroendocrine systems for reproductive functions have diversified as a result of the generation of species-specific paralogs of peptide hormones and their receptors including GnRH and their receptors (GnRHR), which belong to the class A G protein-coupled receptor family. A protochordate, Ciona intestinalis, has been found to possess seven GnRH (tGnRH-3 to -8 and Ci-GnRH-X) and four GnRHR (Ci-GnRHR1 to -4). Moreover, Ci-GnRHR4 (R4) does not bind to any Ciona GnRH and activate any signaling pathways. Here we show novel functional diversification of GnRH signaling pathways via G protein-coupled receptor heterodimerization among Ciona GnRHR. R4 was shown to heterodimerize with R2 specifically in test cells of vitellogenic oocytes by coimmunoprecipitation. The R2-R4 heterodimerization in human embryonic kidney 293 cells cotransfected with R2 and R4 was also observed by coimmunoprecipitation and fluorescent energy transfer analyses. Of particular interest is that the R2-R4 heterodimer decreases the cAMP production in a nonligand-selective manner via shift of activation of Gs protein to Gi protein by R2, compared with R2 monomer/homodimer. Considering that the R1-R4 heterodimer elicits 10-fold more potent Ca2+ mobilization than R1 monomer/homodimer in a ligand-selective manner but does not affect cAMP production, these results indicate that R4 regulates differential GnRH signaling cascades via heterodimerization with R1 and R2 as an endogenous allosteric modulator. Collectively, the present study suggests that the heterodimerization among GnRHR paralogs, including the species-specific orphan receptor subtype, is involved in rigorous and diversified GnRHergic signaling of the protochordate, which lacks a hypothalamus-pituitary gonad axis. PMID- 22294748 TI - The ubiquitin ligase Siah2 regulates PPARgamma activity in adipocytes. AB - Moderate reductions in peroxisome proliferator-activated receptor (PPAR)gamma levels control insulin sensitivity as effectively as activation of PPARgamma in adipocytes by the thiazolidinediones. That observation suggests that PPARgamma activity can be regulated by modulating the amount of PPARgamma protein in adipocytes. Activation of PPARgamma in adipocytes is linked to changes in PPARgamma protein levels via increased degradation of PPARgamma proteins by the ubiquitin proteasome system. Identification of the ubiquitin ligase or ligases that recognize ligand bound PPARgamma is an essential step in determining the physiological significance of the relationship between activation and ubiquitin dependent degradation of PPARgamma. Using an RNA interference-based screen, we identified five RING (really interesting new gene)-type ubiquitin ligases that alter PPARgamma protein levels in adipocytes. Here, we demonstrate that Drosophila seven-in-absentia homolog 2 (Siah2), a mammalian homolog of Drosophila seven-in-absentia, regulates PPARgamma ubiquitylation and ligand-dependent activation of PPARgamma in adipocytes. We also demonstrate that Siah2 expression is up-regulated during adipogenesis and that PPARgamma interacts with Siah2 during adipogenesis. In addition, Siah2 is required for adipogenesis. These data suggest that modulation of PPARgamma protein levels by the ubiquitin ligase Siah2 is essential in determining the physiological effects of PPARgamma activation in adipocytes. PMID- 22294749 TI - FOXL2 is involved in the synergy between activin and progestins on the follicle stimulating hormone beta-subunit promoter. AB - Differential regulation of gonadotropin hormone production in the pituitary is critical for fertility. Activin and progesterone signaling in gonadotrope cells is important for Fshb gene expression. Previously, we reported that synergy between activin and progestins required the binding of SMAD proteins and the progesterone receptor (PR) to the murine Fshb promoter. In this study, we demonstrate that the FOXL2 transcription factor is also necessary for the full synergistic response between activin and progestins. We show that this synergy occurs in a species-specific manner and that multiple elements in the Fshb promoter that bind forkhead box L2 (FOXL2), SMA/mothers against decapentaplegic homologs (SMAD), and PR are required. Furthermore, we demonstrate that FOXL2 can physically interact with PR and SMAD3. Thus, it is likely that protein-protein interactions among FOXL2, SMAD, and PR recruited to the Fshb promoter play a key role in facilitating Fshb transcription before the secondary FSH surge in rodents. PMID- 22294750 TI - Long-term Fgf23 deficiency does not influence aging, glucose homeostasis, or fat metabolism in mice with a nonfunctioning vitamin D receptor. AB - It is still controversial whether the bone-derived hormone fibroblast growth factor-23 (FGF23) has additional physiological functions apart from its well known suppressive actions on renal phosphate reabsorption and vitamin D hormone synthesis. Here we analyzed premature aging, mineral homeostasis, carbohydrate metabolism, and fat metabolism in 9-month-old male wild-type (WT) mice, vitamin D receptor mutant mice (VDR(Delta/Delta)) with a nonfunctioning vitamin D receptor, and Fgf23-/-/VDR(Delta/Delta) compound mutant mice on both a standard rodent chow and a rescue diet enriched with calcium, phosphorus, and lactose. Organ atrophy, lung emphysema, and ectopic tissue or vascular calcifications were absent in compound mutants. In addition, body weight, glucose tolerance, insulin tolerance, insulin secretory capacity, pancreatic beta cell volume, and retroperitoneal and epididymal fat mass as well as serum cholesterol and triglycerides were indistinguishable between vitamin D receptor and compound mutants. In contrast to VDR(Delta/Delta) and Fgf23-/-/VDR(Delta/Delta) mice, which stayed lean, WT mice showed obesity-induced insulin resistance. To rule out alopecia and concomitantly elevated energy expenditure present in 9-month-old VDR(Delta/Delta) and Fgf23-/ /VDR(Delta/Delta) mice as a confounding factor for the lacking effect of Fgf23 deficiency on fat mass, we analyzed whole-body composition in WT, Fgf23-/-, VDR(Delta/Delta), and Fgf23-/-/VDR(Delta/Delta) mice at the age of 4 wk, when the coat in VDR(Delta/Delta) mice is still normal. Whole-body fat mass was reduced in Fgf23-/- mice but almost identical in WT, VDR(Delta/Delta), and Fgf23-/ /VDR(Delta/Delta) mice. In conclusion, our data indicate that Fgf23 has no molecular vitamin D-independent role in aging, insulin signaling, or fat metabolism in mice. PMID- 22294751 TI - Live imaging reveals the link between decreased glucose uptake in ovarian cumulus cells and impaired oocyte quality in female diabetic mice. AB - Maternal diabetes has been demonstrated to adversely affect preimplantation embryo development and pregnancy outcomes. Emerging data suggest that these effects are associated with compromised oocyte quality. However, direct evidence of a pathway by which maternal diabetes exerts its effects on the oocyte is still lacking. Cumulus cells are metabolically coupled to oocytes, and bidirectional communication between them is essential for the development and functions of both compartments. The primary focus of this work was to evaluate the connection between glucose uptake in cumulus cells and oocyte quality in diabetic mice. This experiment has been difficult, because cumulus cells need to be separated from oocytes and labeled with isotope in the process of measuring glucose uptake. Here, we report a method for live imaging glucose transport in single cumulus oocyte complexes using a fluorescent glucose analog (6-(N-(7-nitrobenz-2-oxa-1,3 diazol- 4-yl)amino)-6-deoxyglucose). By tracking the ATP content and spindle/chromosome status in individual oocytes surrounded by cumulus cells with differing glucose uptake activity, we reveal that compromised oocyte quality in diabetic mice is linked to decreased glucose uptake in cumulus cells. PMID- 22294752 TI - Dynamic regulation of Wnt7a expression in the primate endometrium: implications for postmenstrual regeneration and secretory transformation. AB - Despite the vital physiological role of endometrial regeneration during the menstrual cycle and the various pathological implications of abnormal growth of endometrial epithelial cells, the local factors and regulatory mechanisms involved in endometrial regeneration and growth have not been well characterized. Here, we examine the pattern, hormone dependence, and potential functions of Wnt7a (wingless-type MMTV integration site family member 7a), which is known to play a critical role in the formation of the mouse endometrial epithelium during embryonic development, in both human and artificially cycling rhesus macaque endometrium, and using a potent Wnt-antagonist in a mouse model of endometrial regeneration. Wnt7a transcript levels were examined using quantitative real-time PCR and in situ hybridization, and immunohistochemistry was performed to detect Ki-67 and 3,5-bromodeoxyuridine. Stringent, fully conditional Wnt inhibition was achieved by adenoviral expression of Dickkopf-1 during artificial endometrial regeneration in mice. In macaques, Wnt7a expression was confined to the newly formed luminal epithelium (LE) and upper glands during the postmenstrual repair phase. The signal increased in the LE during the proliferative phase but decreased in the upper glands and was undetectable in the glands by the late proliferative phase. Interestingly, Wnt7a was completely suppressed in the LE and remained undetectable in other cell types after 7 d of progesterone treatment. The pattern of Wnt7a expression in the human endometrium was similar to that in macaques. Blockade of Wnt signaling during endometrial regeneration in mice resulted in a dramatic delay in reepithelialization and degeneration of glands and LE. These results strongly suggest, for the first time, a role for Wnt7a in postmenstrual regeneration and proliferation of endometrial glands and LE in primates, and its dramatic suppression by progesterone is likely essential for secretory transformation of the epithelium. PMID- 22294753 TI - Minireview: Glucagon in stress and energy homeostasis. AB - Glucagon is traditionally thought of as an antihypoglycemic hormone, for example in response to starvation. However, it actually increases energy expenditure and has other actions not in line with protection from hypoglycemia. Furthermore, it is often found to be elevated when glucose is also raised, for example in circumstances of psychological and metabolic stress. These findings seem more in keeping with glucagon having some role as a hormone enhancing the response to stress. PMID- 22294754 TI - Pediatric dog bite victims: a need for a continuum of care. AB - The authors assessed the ongoing needs of 34 pediatric dog bite victims and their families 1 month after receiving care in a pediatric emergency department. More than 70% of the parents noted at least 1 new concerning behavior in their children, and more than 85% of the parents also endorsed concerns about their own reactions. Half of the parents believed that children, in general, might benefit from interventions to help with postbite fears and nearly three quarters felt that families would benefit from education regarding dog bite prevention. The majority (85%) of the parents believed that additional supportive services could be offered effectively at emergency department or pediatric office/clinic visits. A template for a dog bite information card is presented. PMID- 22294755 TI - Physical activity for cancer survivors. PMID- 22294756 TI - Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study. AB - OBJECTIVE: To examine the association between chronic use of proton pump inhibitors (PPIs) and risk of hip fracture. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study, which originally recruited from the 11 most populous states in the US. PARTICIPANTS: 79,899 postmenopausal women enrolled in the Nurses' Health Study who provided data on the use of PPIs and other risk factors biennially since 2000 and were followed up to 1 June 2008. MAIN OUTCOME MEASURE: Incident hip fracture RESULTS: During 565,786 person years of follow-up, we documented 893 incident hip fractures. The absolute risk of hip fracture among regular users of PPIs was 2.02 events per 1000 person years, compared with 1.51 events per 1000 person years among non-users. Compared with non-users, the risk of hip fracture among women who regularly used PPIs for at least two years was 35% higher (age adjusted hazard ratio 1.35 (95% confidence interval 1.13 to 1.62)), with longer use associated with increasing risk (P(trend)<0.01). Adjustment for risk factors, including body mass index, physical activity, and intake of calcium did not materially alter this association (hazard ratio 1.36 (1.13 to 1.63)). These associations were also not changed after accounting for reasons for PPI use. The relation between PPI use and fracture differed by smoking history (P(interaction)=0.03). Among current and former smokers, PPI use was associated with greater than 50% increase in risk of fracture, with a multivariate hazard ratio for fracture of 1.51 (1.20 to 1.91). In contrast, among women who never smoked there was no association (multivariate hazard ratio 1.06 (0.77 to 1.46)). In a meta-analysis of these results with 10 prior studies, the pooled odds ratio of hip fracture associated with PPI use was 1.30 (1.25 to 1.36). CONCLUSION: Chronic use of PPIs is associated with increased risk of hip fracture, particularly among women with a history of smoking. PMID- 22294758 TI - Functional and haemodynamic recovery after implantation of continuous-flow left ventricular assist devices in comparison with pulsatile left ventricular assist devices in patients with end-stage heart failure. AB - AIMS: Caused by ageing of the population, better survival from ischaemic heart disease, and improved treatment of chronic heart disease, the incidence of heart failure has increased enormously. Worldwide, left ventricular assist devices (LVADs) are increasingly being used as a bridge or alternative to heart transplantation. In this study, we investigated whether there is difference in functional and haemodynamic recovery after implantation of pulsatile and continuous-flow pumps. METHODS AND RESULTS: We compared laboratory and echocardiographic data and exercise performance in patients with end-stage heart failure, before and 3 months after implantation of pulsatile and continuous-flow LVADs. A significant improvement in all laboratory parameters after implantation of both types of LVADs was seen, as well as a significant decrease in heart rate and LV dimensions, indicating better haemodynamics and cardiac recompensation. This improvement was better for the pulsatile device, probably due to higher plasma levels and higher LV dimensions before implantation. Exercise capacity strongly improved: 3 months after implantation of pulsatile and continuous-flow LVADs, peak VO(2) was 20.2 +/- 4.8 vs. 18.3 +/- 4.8 mL/kg/min (P = 0.09) (53 +/- 12 vs. 49 +/- 11% of predicted for age and gender) (P = 0.28). CONCLUSION: Pulsatile and continuous-flow LVADs result in extensive haemodynamic recovery and exercise performance compatible with daily life activities. Exercise performance with continuous-flow LVADs is equal to that with pulsatile devices. This, in combination with improved survival of the newer devices, allows its use as an alternative to heart transplantation in selected patients. PMID- 22294757 TI - Physical activity for cancer survivors: meta-analysis of randomised controlled trials. AB - OBJECTIVE: To systematically evaluate the effects of physical activity in adult patients after completion of main treatment related to cancer. DESIGN: Meta analysis of randomised controlled trials with data extraction and quality assessment performed independently by two researchers. DATA SOURCES: Pubmed, CINAHL, and Google Scholar from the earliest possible year to September 2011. References from meta-analyses and reviews. STUDY SELECTION: Randomised controlled trials that assessed the effects of physical activity in adults who had completed their main cancer treatment, except hormonal treatment. RESULTS: There were 34 randomised controlled trials, of which 22 (65%) focused on patients with breast cancer, and 48 outcomes in our meta-analysis. Twenty two studies assessed aerobic exercise, and four also included resistance or strength training. The median duration of physical activity was 13 weeks (range 3-60 weeks). Most control groups were considered sedentary or were assigned no exercise. Based on studies on patients with breast cancer, physical activity was associated with improvements in insulin-like growth factor-I, bench press, leg press, fatigue, depression, and quality of life. When we combined studies on different types of cancer, we found significant improvements in body mass index (BMI), body weight, peak oxygen consumption, peak power output, distance walked in six minutes, right handgrip strength, and quality of life. Sources of study heterogeneity included age, study quality, study size, and type and duration of physical activity. Publication bias did not alter our conclusions. CONCLUSIONS: Physical activity has positive effects on physiology, body composition, physical functions, psychological outcomes, and quality of life in patients after treatment for breast cancer. When patients with cancer other than breast cancer were also included, physical activity was associated with reduced BMI and body weight, increased peak oxygen consumption and peak power output, and improved quality of life. PMID- 22294759 TI - Ejection fraction and outcomes in patients with atrial fibrillation and heart failure: the Loire Valley Atrial Fibrillation Project. AB - AIMS: Heart failure (HF) increases the risk of stroke and thrombo-embolism (TE) in non-valvular atrial fibrillation (NVAF), and is incorporated in stroke risk stratification scores. We aimed to establish the role of ejection fraction (EF) in risk prediction in patients with NVAF and HF. METHODS AND RESULTS: Patients with NVAF, history of HF, and measured EF were included in a retrospective analysis. Patients with HF and preserved ejection fraction (HFPEF) were defined as those with clinical HF and EF >=50% in this study. Among 7156 patients with NVAF, 1276 (17.8%) patients with HF and measured EF were included. Of these, 747/1276 (58.5%) patients were on vitamin K antagonists. The stroke/TE event rate per 100 person-years was 1.05 [95% confidence interval (CI) 0.87-1.25]. Patients with HFPEF were more likely to be female (P < 0.001), older (P < 0.001), and hypertensive (P < 0.001), and less likely to have prior vascular disease (P < 0.001). There were no differences in rates of stroke (P = 0.17) and stroke/TE (P = 0.11) between patients with HFPEF and those with HF and reduced EF. There were no significant differences in rates of all-cause mortality when patients were stratified by EF. In multivariate analyses, only previous stroke (hazard ratio 2.36, 95% CI 1.45-3.86) and vascular disease (1.57, 1.07-2.30) increased the risk of stroke/TE amongst NVAF patients with HF, but EF <35% did not (0.75, 0.44 1.30). CONCLUSION: In NVAF patients with HF, there were no differences in rates of stroke, TE, or death between EF categories. Only previous stroke and vascular disease (and not decreased EF) independently increased risk of stroke/TE in multivariate analyses. PMID- 22294760 TI - Colorectal cancer genetics: from candidate genes to GWAS and back again. PMID- 22294761 TI - COGENT (COlorectal cancer GENeTics) revisited. AB - Many colorectal cancers (CRCs) develop in genetically susceptible individuals most of whom are not carriers of germ line mismatch repair or APC gene mutations and much of the heritable risk of CRC appears to be attributable to the co inheritance of multiple low-risk variants. The accumulated experience to date in identifying this class of susceptibility allele has highlighted the need to conduct statistically and methodologically rigorous studies and the need for the multi-centre collaboration. This has been the motivation for establishing the COGENT (COlorectal cancer GENeTics) consortium which now includes over 20 research groups in Europe, Australia, the Americas, China and Japan actively working on CRC genetics. Here, we review the rationale for identifying low penetrance variants for CRC and the current and future challenges for COGENT. PMID- 22294763 TI - Gene expression variations: potentialities of master regulator polymorphisms in colorectal cancer risk. AB - Colorectal cancer (CRC) is one of the most common cancers worldwide with a peak of incidence in industrialised countries. It is a complex disease related to environmental and genetic risk factors. Low-penetrance genetic variations contribute significantly to sporadic and familial form of CRC. Genome-wide association studies (GWAS) have uncovered numerous robust associations between common variants and CRC risk; only a few of those were protein altering non synonymous polymorphisms. One of the hypotheses is that non-coding and intergenic variants may change the expression levels of one or several target genes and, thus, account for a fraction of phenotypic differences, including susceptibility to CRC. Such genetic variations have been detected as expression quantitative loci (eQTLs) that show linkage/association to a large number of genes and have been defined as "master regulators of transcription". In the present work, we overview the potentialities to use results from GWAS and eQTL studies in the identification as well as investigation of master regulators in CRC susceptibility. PMID- 22294762 TI - Seeking genetic susceptibility variants for colorectal cancer: the EPICOLON consortium experience. AB - The EPICOLON consortium was initiated in 1999 by the Gastrointestinal Oncology Group of the Spanish Gastroenterology Association. It recruited consecutive, unselected, population-based colorectal cancer (CRC) cases and control subjects matched by age and gender without personal or familial history of cancer all over Spain with the main goal of gaining knowledge in Lynch syndrome and familial CRC. This epidemiological, prospective and multicentre study collected extensive clinical data and biological samples from ~2000 CRC cases and 2000 controls in Phases 1 and 2 involving 25 and 14 participating hospitals, respectively. Genetic susceptibility projects in EPICOLON have included candidate-gene approaches evaluating single-nucleotide polymorphisms/genes from the historical category (linked to CRC risk by previous studies), from human syntenic CRC susceptibility regions identified in mouse, from the CRC carcinogenesis-related pathways Wnt and BMP, from regions 9q22 and 3q22 with positive linkage in CRC families, and from the mucin gene family. This consortium has also participated actively in the identification 5 of the 16 common, low-penetrance CRC genetic variants identified so far by genome-wide association studies. Finishing their own pangenomic study and performing whole-exome sequencing in selected CRC samples are among EPICOLON future research prospects. PMID- 22294764 TI - Genetic polymorphisms in fatty acid metabolism genes and colorectal cancer. AB - Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Epidemiological risk factors for CRC included dietary fat intake; consequently, the role of genes in the fatty acid biosynthesis and metabolism pathways is of particular interest. Moreover, hyperlipidaemia has been associated with different type of cancer and serum lipid levels could be affected by genetic factors, including polymorphisms in the lipid metabolism pathway. The aim of this study is to assess the association between single-nucleotide polymorphisms (SNPs) in fatty acid metabolism genes, serum lipid levels, body mass index (BMI) and dietary fat intake and CRC risk; 30 SNPs from 8 candidate genes included in fatty acid biosynthesis and metabolism pathways were genotyped in 1780 CRC cases and 1864 matched controls from the Molecular Epidemiology of Colorectal Cancer study. Information on clinicopathological characteristics, lifestyle and dietary habits were also obtained. Logistic regression and association analysis were conducted. Several LIPC (lipase, hepatic) polymorphisms were found to be associated with CRC risk, although no particular haplotype was related to CRC. The SNP rs12299484 showed an association with CRC risk after Bonferroni correction. We replicate the association between the T allele of the LIPC SNP rs1800588 and higher serum high density lipoprotein levels. Weak associations between selected polymorphism in the LIPC and PPARG genes and BMI were observed. A path analysis based on structural equation modelling showed a direct effect of LIPC gene polymorphisms on colorectal carcinogenesis as well as an indirect effect mediated through serum lipid levels. Genetic polymorphisms in the hepatic lipase gene have a potential role in colorectal carcinogenesis, perhaps though the regulation of serum lipid levels. PMID- 22294765 TI - The influence of selenium and selenoprotein gene variants on colorectal cancer risk. AB - Colorectal cancer (CRC) is a major cause of mortality throughout the world and risk of CRC is known to be modulated by nutritional factors. Low intake of the micronutrient selenium (Se) has been implicated as a risk factor in CRC, and in this article we describe the biochemical functions of selenium in selenoproteins, review the evidence for an association of selenium status with CRC and adenoma risk and describe the genetic epidemiological data on selenoprotein genes and CRC risk. Epidemiological evidence linking Se intake to CRC risk is limited but there is strong evidence for a link to adenoma risk. Two studies show an association between a genetic variant in the selenoprotein S gene and CRC risk. Selenium intake modulates selenoprotein expression in the colon, especially selenoproteins W, H, M, 15 kDa selenoprotein and glutathione peroxidase 1, and downstream targets such as endoplasmic reticulum stress response, oxidative stress and inflammatory pathways. We hypothesis that Se, through the selenoproteins, plays a key role in the ability of colonic epithelial cells to respond to microbial and oxidative challenges and that a combination of low Se intake and SNP in selenoprotein genes can impair that role and so lead to increased risk of pre neoplastic lesions. There is a need for both further studies of selenoprotein function in the colon and major genetic epidemiological and intervention studies. PMID- 22294766 TI - The role of ABC transporters in progression and clinical outcome of colorectal cancer. AB - Worldwide, colorectal cancer (CRC) is the third most common cancer, with the highest mortality rates occurring in Central Europe. The use of chemotherapy to treat CRC is limited by the inter-individual variability in drug response and the development of cancer cell resistance. ATP-binding cassette (ABC) transporters play a crucial role in the development of resistance by the efflux of anticancer agents outside of cancer cells. The aim of this study was to explore transcript levels of all human ABCs in tumours and non-neoplastic control tissues from CRC patients collected before the first line of treatment by 5-fluorouracil (5-FU) containing regimen. The prognostic potential of ABCs was evaluated by the correlation of transcript levels with clinical factors. Relations between transcript levels of ABCs in tumours and chemotherapy efficacy were also addressed. The transcript profile of all known human ABCs was assessed using real time polymerase chain reaction with a relative standard curve. The majority of the studied ABCs were down-regulated or unchanged between tumours and control tissues. ABCA12, ABCA13, ABCB6, ABCC1, ABCC2 and ABCE1 were up-regulated in tumours versus control tissues. Transcript levels of ABCA12, ABCC7 and ABCC8 increased in direction from colon to rectum. Additionally, transcript levels of ABCB9, ABCB11, ABCG5 and ABCG8 followed the reverse significant trend, i.e. a decrease in direction from colon to rectum. The transcript level of ABCC10 in tumours correlated with the grade (P = 0.01). Transcript levels of ABCC6, ABCC11, ABCF1 and ABCF2 were significantly lower in non-responders to palliative chemotherapy in comparison with responders. The disease-free interval of patients treated by adjuvant chemotherapy was significantly shorter in patients with low transcript levels of ABCA7, ABCA13, ABCB4, ABCC11 and ABCD4. In conclusion, ABCC11 may be a promising candidate marker for a validation study on 5-FU therapy outcome. PMID- 22294767 TI - Ancestral susceptibility to colorectal cancer. AB - Every year, approximately 1 million new colorectal cancer (CRC) cases are diagnosed and about half a million people worldwide die due to this cancer. Known differences in CRC incidence rates are mainly attributed to differences in diet and other environmental factors represented, among others, by nutrition-related complex diseases (e.g. obesity and diabetes mellitus type II). Within the last years, it has become evident that environmental risk factors can be complemented by a genetic component when considering the risk of CRC. For example, a number of polymorphisms are known to be associated with an increased risk of obesity and obesity is a risk factor for CRC. Several studies have shown that the 'ancestral susceptibility model' can be reasonably applied to nutrition-related complex diseases such as obesity. The work in hand shortly discusses whether the ancestral-susceptibility model can also be applied to CRC as a nutrition-related complex disease. PMID- 22294768 TI - Role of variations within microRNA-binding sites in cancer. AB - Over 2000 microRNA (miRNA) sequences from different species have been submitted to the miRBase, the central online repository for miRNAs, making a total of 5071 miRNA loci, expressing 5922 distinct mature miRNA sequences. In this review, we have addressed the importance of the genetic variations in humans affecting miRNAs, their target genes and the genes involved in miRNA processing for individual risk of cancer, with particular emphasis on colorectal cancer. In fact, the number of studies suggesting that individual predisposition to cancer is modulated by genetic polymorphisms affecting the biogenesis of miRNA and the interaction between miRNAs and targets has risen steeply in the last few years. We also report the first evidence that variant alleles of single-nucleotide polymorphisms (SNPs) within miRNA genes and miRNA targets, previously associated with the risk of cancer, behave differently when tested in functional studies. The SNPs belonging to the miRNA world are certainly contributing to new insights in the field of the genetic predisposition to disease. PMID- 22294769 TI - Mutations and polymorphisms in TP53 gene--an overview on the role in colorectal cancer. AB - A functionally normal TP53 is essential to protect organisms from developing cancer. Somatic mutations in the gene represent one of the highest recurring perturbations in human tumours, including colorectal cancer (CRC). However, the variegated phenotype of wide spectrum of somatic mutations in TP53 and the complexity of the disease prevent a straight interpretation of the mutational analysis in tumours. In addition to the presence of somatic mutations, polymorphic features of the gene may also contribute to alteration of the normal TP53 functioning and variants, mainly in the form of single nucleotide polymorphisms, can be expected to impact susceptibility to sporadic CRC. In the present study, we reviewed the potential role of alterations in the TP53 gene, both somatic mutations and inherited sequence variations, in predisposition to CRC and in the prognosis and response to therapy. The available data from association studies have mostly shown contradictory outcomes. The majority of the studies were based on limited sample sizes and focussed on a limited number of polymorphisms, with main being the rs1042522 (Arg72Pro). Thus far, there is no possible generalisation of the role of TP53 as also a predictor of therapeutic response and prognosis. The effects of TP53, and its abnormalities, on the response of tumours to cytotoxic drugs, radiation and chemoradiation are complex. However, from studies it is emerging that the inherited genetics of TP53 pathway components could be utilised to further define patient populations in their abilities to induce p53 activity in response to either DNA damaging or p53 targeted therapies. PMID- 22294770 TI - Investigation of the effects of DNA repair gene polymorphisms on the risk of colorectal cancer. AB - Despite their prime candidate status, polymorphisms near genes involved in DNA repair or in other functions related to genome stability have been conspicuously under-represented in the significant associations reported from genome-wide association studies (GWAS) of cancer susceptibility. In this study, we assessed a set of single-nucleotide polymorphisms (SNPs) near 157 DNA repair genes in three colorectal cancer (CRC) GWAS. Although no individual SNP showed evidence of association, the set of SNPs as a whole was associated with colorectal cancer risk. When candidate SNPs were examined, our data did not support most of the previously reported associations with CRC susceptibility, an exception being an effect of the MLH1 promoter SNP -93G>A (rs1800734). Rare variants in CHEK2 (I157T and possibly del1100C) also appear to be associated with CRC risk. Overall, the absence to date of disease-associated DNA repair SNPs in cancer GWAS may be explained by a combination of the following: (i) many loci with individually very small effects on risk; (ii) rare alleles of moderate effect and (iii) subgroups of CRC, such as those with microsatellite instability, associated with specific variants. It will be particularly intriguing to determine whether any GWAS across cancer types identify DNA variants that predispose to cancers of more than one site. PMID- 22294771 TI - Differences in nucleotide excision repair capacity between newly diagnosed colorectal cancer patients and healthy controls. AB - Alteration of DNA integrity is a potential cause of cancer and it is assumed that reduced DNA repair capacity and accumulation of DNA damage may represent intermediate markers in carcinogenesis. In this case-control study, DNA damage and nucleotide excision repair capacity (NER-DRC) were assessed in association with sporadic colorectal cancer (CRC). Both parameters were quantified by comet assay in blood cells of 70 untreated incident patients and 70 age-matched healthy controls. mRNA expression and polymorphisms in relevant NER genes were concurrently analyzed. The aim of this study was to characterize incident CRC patients for NER-DRC and to clarify possible relations between investigated variables. Comet assay and mRNA expression analysis showed that CRC patients differ in repair capacity as compared to controls. Patients had a lower NER-DRC and simultaneously they exhibited higher endogenous DNA damage (for both P < 0.001). Accumulation of DNA damage and decreasing NER-DRC behaved as independent modulating parameters strongly associated with CRC. Expression levels of 6 out of 9 studied genes differed between groups (P <= 0.001), but none of them was related to DRC or to any of the studied NER polymorphisms. However, in patients only, XPC Ala499Val modulated expression levels of XPC, XPB and XPD gene, whereas XPC Lys939Gln was associated with XPA expression level in controls (for all P < 0.05). This study provides evidence on altered DRC and DNA damage levels in sporadic CRC and proposes the relevance of the NER pathway in this malignancy. Further, alterations in a complex multigene process like DNA repair may be better characterized by functional quantification of repair capacity than by quantification of individual genes transcripts or gene variants alone. PMID- 22294772 TI - In vitro stability of APC gene sequences and the influence of DNA repair status. AB - APC is a key 'gatekeeper' gene in colorectal tumorigenesis. The high frequency of APC defects observed in colorectal cancer tissue is the result of selective growth advantage of cells with loss-of-function mutations at that locus. However, mutations may also arise due to inherent sequence instability. Defective DNA mismatch repair (MMR) and base excision repair (BER) also contribute to colorectal carcinogenesis and may compound such instability. To avoid the effect of clonal selective advantage imparted by APC mutation in cancer cells, we assessed in vitro APC mutation frequency in cell lines of lymphoid lineage to investigate the influence of defective MMR and BER. In DNA repair proficient cells, we observed substantially greater inherent sequence instability in APC gene coding sequences compared to reference sequences. Surprisingly, however, this difference was abrogated in MMR defective lines. We also found greater mutation frequency at exonic DNA sequences outwith the APC region in cells defective for either MMR or BER defects. The underlying propensity for mutation at the APC gene is intriguing, while the greater frequency of mutation in cells defective for DNA repair has relevance to understanding events leading to colorectal cancer and other malignancies. PMID- 22294773 TI - A review of the genetic background and tumour profiling in familial colorectal cancer. AB - Inherited predisposition plays a role in 10-30% of colorectal cancer (CRC) cases. Of the large families with a clearly positive family history of CRC, ~40% is not affected by known CRC syndromes. The existence of families with unexplained forms of inherited CRC--familial CRC--suggests the presence of still unknown high- or moderate-risk CRC predisposing factors. While the genomic profiles of sporadic CRCs have been studied extensively, few studies have analysed the tumour profiles of hereditary or familial CRC. Here, we review recent advances in genomic tumour profiling in familial CRC in comparison with sporadic CRC. In addition, we discuss the role of known CRC risk factors in familial CRC. PMID- 22294774 TI - Role of the microenvironment in the tumourigenesis of microsatellite unstable and MUTYH-associated polyposis colorectal cancers. AB - Two forms of genomic instability can be distinguished in colorectal cancer (CRC) tumourigenesis. One is characterised by pronounced chromosomal instability (CIN), while the other relates to alterations produced at the nucleotide level that preferentially target microsatellite sequences. Tumours developing under the latter form of genomic instability possess a microsatellite instability-high (MSI H) phenotype due to inactivation of the DNA mismatch repair system. The most recently described CRC syndrome, MUTYH-associated polyposis (MAP), shares characteristics with both MSI-H and CIN cancers. MAP carcinomas develop from the impairment of the base excision repair system, where MUTYH is involved, but also present a peculiar form of CIN. Several clinicopathological characteristics of MSI-H and MAP CRCs overlap such as tumour location, clinical prognosis and histological features. We propose that MSI-H and MAP CRCs are particularly prone to interact with their tumour microenvironment. A great deal of this interaction is probably stimulated by the immunogenic character of those tumours, known to possess a high mutagenic potential. The accumulation of mutations in coding regions of the genome of MSI-H and MAP carcinomas is likely to translate into a surplus of neo-antigens that trigger an anti-tumour immune response. The immune system constitutes thus an important vector of selective pressure that favours the outgrowth of tumour clones with immune-evasive phenotypes. In this review, we summarise the evidence for the influence of the tumour microenvironment in MSI-H and MAP tumourigenesis. Furthermore, we discuss how particular features of MSI-H and MAP CRCs can be exploited for the development of therapeutic strategies for affected patients. PMID- 22294775 TI - Health indicators in Europe: availability and data needs. AB - BACKGROUND: The European Union (EU) lacks adequate capacity for public health monitoring. The creation of a stable European Health Information System would help Member States to carry out evidence-based health policy. Such a system would also benefit EU health priorities by providing European wide comparable information. This study is the first comprehensive assessment of the availability of general health data in Europe. METHODS: The main aim was to assess the availability of the European Community Health Indicators (ECHI) in each EU Member State. This was done by means of a review of international health databases, an online survey and face-to-face discussions with experts in 31 European countries. RESULTS: The European average availability score for all ECHI indicators was 74% ranging from 56% to 84%. In most countries, about half of the ECHI indicators can be derived from routinely collected health information. This is true for demographic information, mortality and hospital discharge-based morbidity. However, many important ECHI indicators are lacking in most European countries. These include population representative data for health determinants, the provision and use of health care services, injuries, the quality of health care and health promotion. CONCLUSION: Valid health information is essential for improving people's health across Europe. There is an urgent need to develop harmonized methods for gathering and disseminating representative health data. These methods should be developed jointly by DG Health and Consumers, Eurostat and EU Member States. PMID- 22294776 TI - One dose of cyclosporine A is protective at initiation of folic acid-induced acute kidney injury in mice. AB - BACKGROUND: In most patients, acute kidney injury (AKI) represents the combined effects of ischemic, toxic and inflammatory insults. No effective pharmacologic interventions have been developed to prevent AKI or to improve outcomes to date. Cyclosporine A (CsA) is a calcineurin inhibitor that mediates T-cell receptor signaling, suppresses inflammatory cytokine expression and inhibits leukocyte migration. It is also a potent inhibitor of mitochondrial permeability, protecting cells from death. These properties make it a potentially valuable drug to prevent or treat AKI. It does, however, carry a significant risk of nephrotoxicity, especially with chronic use. By contrast, a single dose of CsA may be protective while limiting the risk of nephrotoxicity. METHODS: We conducted a controlled animal experiment in male CD-1 mice. Specifically, mice were subjected to folic acid (FA)-induced AKI and then randomly assigned to sham operation or one of three dosage of CsA treatment groups. Results Intraperitoneal injection of FA consistently induced AKI. Serum interleukin (IL)-6 and urinary neutrophil gelatinase-associated lipocalin (NGAL) rose 1 day after FA injection. Compared to sham treatment, one dose (1 and 5 mg/kg body weight) of CsA significantly reduced kidney tubular cell apoptosis, serum creatinine, blood urea, serum IL-6 and urinary NGAL 2 days after FA injection. It was also shown to block the inflammatory mediator tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) expression, nuclear factor kappa-B (NFkappaB) activation, inflammatory cell infiltration and interstitial fibrosis 14 days after treatment in a dose-dependent fashion. By contrast, a dose of 10 mg/kg body weight CsA resulted in nephrotoxicity in the setting of FA-induced AKI. CONCLUSIONS: A single dose of CsA, currently used for organ transplant, significantly protects mice from FA-induced AKI, presumably through inhibition of cell death, inflammatory reaction, interstitial cell infiltration and fibrosis. The protective effects have the potential to open a completely new line of investigation in the prevention and treatment of AKI. PMID- 22294777 TI - Proof-of-principle study to detect metabolic changes in peritoneal dialysis effluent in patients who develop encapsulating peritoneal sclerosis. AB - BACKGROUND: Prolonged peritoneal dialysis (PD) therapy can result in the development of encapsulating peritoneal sclerosis (EPS), characterized by extensive sclerosis of the peritoneum with bowel adhesions often causing obstruction. METHODS: As a proof-of-principle study, holistic profiling of endogenous metabolites has been applied in a prospective collection of PD effluent collected in multiple UK renal centres over 6 years in order to investigate metabolic differences in PD effluent between PD therapy patients who later developed clinically defined EPS (n = 11) and controls, who were matched for PD vintage, age and gender (n = 11). RESULTS: 'Fit-for-purpose' analytical methods employing gas chromatography-mass spectrometry (MS), direct injection MS and quality control samples were developed and validated. These methods were applied in a proof-of-principle study to define metabolic differences in PD effluent related to subsequent development of EPS. Changes in amino acids, amines and derivatives, short-chain fatty acids and derivatives and sugars were observed prior to EPS developing, and changes in the metabolomic profiles could be detected. CONCLUSION: There is potential for applying metabolic profiles to identify patients at risk of developing EPS although long-term prospective studies with larger patient cohorts are required. PMID- 22294778 TI - Comparative impact of smoke-free legislation on smoking cessation in three European countries. AB - BACKGROUND: Little is known about the differential impact of comprehensive and partial smoke-free legislation on smoking cessation. This study aimed to examine the impact of comprehensive smoke-free workplace legislation in Ireland and England, and partial hospitality industry legislation in the Netherlands on quit attempts and quit success. METHODS: Nationally representative samples of 2,219 adult smokers were interviewed in three countries as part of the International Tobacco Control (ITC) Europe Surveys. Quit attempts and quit success were compared between period 1 (in which smoke-free legislation was implemented in Ireland and the Netherlands) and period 2 (in which smoke-free legislation was implemented in England). RESULTS: In Ireland, significantly more smokers attempted to quit smoking in period 1 (50.5%) than in period 2 (36.4%) (p < 0.001). Percentages of quit attempts and quit success did not change significantly between periods in the Netherlands. English smokers were significantly more often successful in their quit attempt in period 2 (47.3%) than in period 1 (26.4%) (p = 0.011). In the first period there were more quit attempts in Ireland than in England and fewer in the Netherlands than in Ireland. Fewer smokers quitted successfully in the second period in both Ireland and the Netherlands than in England. CONCLUSION: The comprehensive smoke-free legislation in Ireland and England may have had positive effects on quit attempts and quit success respectively. The partial smoke-free legislation in the Netherlands probably had no effect on quit attempts or quit success. Therefore, it is recommended that countries implement comprehensive smoke-free legislation. PMID- 22294779 TI - Comprehensive smoke-free policies attract more support from smokers in Europe than partial policies. AB - BACKGROUND: Support for smoke-free policies increases over time and particularly after implementation of the policy. In this study we examined whether the comprehensiveness of such policies moderates the effect on support among smokers. METHODS: We analysed two waves (pre- and post-smoke-free legislation) of the International Tobacco Control (ITC) surveys in France, Germany, and the Netherlands, and two pre-legislation waves of the ITC surveys in UK as control. Of 6,903 baseline smokers, 4,945 (71.6%) could be followed up and were included in the analyses. Generalised Estimating Equations (GEE) were used to compare changes in support from pre- to post-legislation to the secular trend in the control country. Multiple logistic regression models were employed to identify predictors of individual change in support. FINDINGS: In France, the comprehensive smoking ban was associated with sharp increases in support for a total smoking ban in drinking establishments and restaurants that were above secular trends. In Germany and the Netherlands, where smoke-free policies and compliance are especially deficient in drinking establishments, only support for a total smoking ban in restaurants increased above the secular trend. Notable prospective predictors of becoming supportive of smoking bans in these countries were higher awareness of cigarette smoke being dangerous to others and weekly visiting of restaurants. CONCLUSIONS: Our findings suggest that smoke-free policies have the potential to improve support once the policy is in place. This effect seems to be most pronounced with comprehensive smoking bans, which thus might be the most valid option for policy-makers despite their potential for creating controversy and resistance in the beginning. PMID- 22294780 TI - Predictors of car smoking rules among smokers in France, Germany and the Netherlands. AB - BACKGROUND: As exposure to tobacco smoke pollution (TSP) has been identified as a cause of premature death and disease in non-smokers, and studies have demonstrated that smoking in cars produces high levels of TSP, this study will investigate smokers' rules for smoking in their cars, and predictors of car smoking rules, including potentially modifiable correlates. METHODS: Data were drawn from nationally representative samples of current smokers from the International Tobacco Control Policy Evaluation Project surveys in France (2007), Germany (2007), and the Netherlands (2008). Smokers in France and Germany were asked about smoking rules in their cars, and smokers in the Netherlands were asked about smoking rules in cars carrying children. RESULTS: In France and Germany, 59% and 52% of smokers respectively, allowed smoking in their cars. In the Netherlands, 36% of smokers allowed smoking in cars carrying children. Predictors of allowing smoking in cars included: being a daily vs. non-daily smoker, being younger vs. older age, having no (young) children in the home, being a heavier smoker, and allowing smoking in the home. In the Netherlands, smokers who agreed that TSP is dangerous to non-smokers were less likely to allow smoking in cars carrying children. CONCLUSION: Overall, a sizeable proportion of smokers allowed smoking in their cars across the three countries. Media campaigns with information about the dangers of TSP may increase the adoption of smoke-free cars. These media campaigns could target smokers who are most likely to allow smoking in cars. PMID- 22294781 TI - Smoking cessation interventions from health care providers before and after the national smoke-free law in France. AB - BACKGROUND: Smoking cessation advice from health care providers (HCP) is well known to be associated with increased quitting. This study sought to understand the extent to which smokers in France who visited a HCP around the time of the implementation of the national ban on smoking received encouragement to quit from a HCP and what kinds of intervention were provided. HCP may have a unique opportunity during the implementation phase of smoke-free laws to address their patients' smoking behaviours to increase the likelihood of success at a time when smokers' readiness and interest in quitting may be higher. METHODS: Telephone interviews were conducted among adult smokers (n = 1067) before and after the two phase (2007 and 2008) national ban on indoor smoking as part of the International Tobacco Control (ITC) France Survey. In the survey, smokers were asked whether they had visited a HCP in the past 6 months and, if so, whether they had received cessation encouragement, and/or other interventions to support quitting such as prescriptions for stop-smoking medication. RESULTS: Most smokers (61%) reported visiting a HCP in the 6 months prior to the first phase of the national smoke free ban, and 58% after the time of the hospitality ban. Of these, most reported they did not receive any assistance from a HCP before (54%) or after (64%) the smoke-free law. Among those who reported an intervention, the most common were only encouragement to quit (58% in Wave 1 and 49% in Wave 2), or receiving both encouragement and a pamphlet (31% in both Wave 1 and 2). The combination of prescriptions for stop-smoking medicine and encouragement to quit increased from 8% in 2007 to 22% in 2008. The smokers who received an intervention were more likely (OR 1.9, 95% CI: 1.2-2.9) to report that they were thinking about quitting. DISCUSSION: This study demonstrates that HCP in France are well positioned to provide smoking cessation encouragement and other interventions to a majority of smokers and thus the importance of taking measures to increase their involvement, particularly when population-level tobacco control policies, such as smoke-free laws, are being implemented. PMID- 22294782 TI - Outdoor smoking behaviour and support for outdoor smoking restrictions before and after France's national smoking ban. AB - BACKGROUND: On January 1, 2008, the French government implemented a national ban on indoor smoking in hospitality venues. Survey results indicate the indoor ban has been successful at dramatically reducing indoor smoking; however, there are reports of an increased number of outdoor hospitality spaces (patios) where smoking can take place. This study sought to understand if the indoor ban simply moved smoking to the outdoors, and to assess levels of support for smoking restrictions in outdoor hospitality settings after the smoke-free law. METHODS: Telephone interviews were conducted among 1067 adult smokers before and after the 2008 indoor ban as part of the International Tobacco Control (ITC) France Survey. Among other topics, this survey measures how the smoking ban has influenced smoking behaviour relevant to outdoor sections of hospitality venues. In addition, 414 non-smoking adults and 164 respondents who had quit smoking between waves were also asked about support for outdoor smoking restrictions. RESULTS: Reported smoking outdoors at cafes/pubs/bars increased from 33.6% of smokers at Wave 1 to 75.9% at Wave 2. At restaurants, smoking outdoors increased from 28.9% to 59.0%. There was also an increase in reported non-smoking for both visits to cafes/pubs/bars, and restaurants from 13.4% to 24.7%, and 30.4% to 40.8% respectively. The majority of smokers (74.5%), non-smokers (89.4%) and quitters (74.0%) support a partial or complete ban on smoking in outdoor areas of restaurants. CONCLUSION: The indoor smoking ban moved smoking to outdoor spaces; however, the ban is also associated with increased non-smoking behaviour. The majority of respondents support outdoor smoking restrictions in patio environments. PMID- 22294783 TI - Do smokers in Europe think all cigarettes are equally harmful? AB - BACKGROUND: Despite the ban on misleading descriptors such as light or mild cigarettes in Europe, there are still widespread misperceptions of the relative harmfulness of different brands of cigarettes among smokers. This study examined the extent to which smokers in three European countries believed that some cigarette brands are less harmful and why, using data from the International Tobacco Control (ITC) Europe surveys. METHODS: Cross-sectional analyses were completed among nationally representative samples of 4,956 current smokers (aged >= 18) from Germany (n = 1,515), France (n = 1,735) and the United Kingdom (n = 1,706) conducted between September 2006 and November 2007. Logistic regression models examined whether outcomes, including beliefs that some cigarettes could be less harmful than others, varied by socio-demographic and country of residence. FINDINGS: Around a quarter of smokers in the UK and France, and a third in Germany believed some cigarettes are less harmful than others. Overall, of smokers who falsely believed that some cigarettes are less harmful, 86.3% thought that tar/nicotine yields, 48.7% taste, and 40.4% terms on packs such as 'smooth' or 'ultra' indicated less harmful brands. About a fifth of smokers across all countries chose their brand based on health reasons, and a similar proportion gave tar yields as a reason for choosing brands. CONCLUSIONS: Our research suggests that the current European Tobacco Products Directive is inadequate in eliminating misperceptions about the relative risk of brand descriptors on cigarettes. There is therefore an urgent need to protect smokers in Europe from these misperceptions via stronger measures such as plain packaging regulations. PMID- 22294784 TI - Struggling to make ends meet: exploring pathways to understand why smokers in financial difficulties are less likely to quit successfully. AB - BACKGROUND: In high-income countries, those with low-to-middle incomes have been observing stagnating median wages and marginal improvements in their living standards. Smokers in financial difficulties appear to be less likely to quit smoking. Understanding the reasons for this is essential to intervening to improve cessation outcomes in this population, and reduce smoking-related health inequalities. METHODS: We used longitudinal data from Waves 4 to 7 of the ITC Four Country Survey (ITC-4), and included those with data from at least two consecutive waves. Associations between financial difficulties and making a quit attempt, and quit success were analysed using generalised estimating equations, with adjustment for confounders. Mediation analysis was conducted to identify potential mediators of the observed effects of financial difficulties on cessation outcomes. RESULTS: Having financial difficulties had little impact on making quit attempts (adjusted OR 0.84, 95% CI 0.70-1.01). Smokers with financial difficulties were substantially less likely to succeed at quitting (adjusted OR 0.55, 95% CI 0.39-0.76); an effect which was consistent over the survey years. Among the potential mediators examined, those relating to cognition of health related and quality of life-related consequences of smoking were the most important mediators, though the proportion of the effect mediated by the largest mediator was small (6.8%). CONCLUSION: Having financial difficulties remains an important barrier to smokers achieving quit success. This effect does not appear to be due to anticipated factors such as reduced use of cessation services or treatment. Further research is required to determine strong mediators of the financial difficulties effect on quit success and to tailor more effective cessation programmes. PMID- 22294785 TI - Assessment of a 'fast-track' referral service for intrauterine contraception following early medical abortion. AB - BACKGROUND: A 'fast-track' referral system for intrauterine contraception was established in 2007 between the medical abortion service at the Royal Infirmary of Edinburgh and the principal family planning clinic (FPC) in Edinburgh. METHODS: Case note review of women fast-tracked for intrauterine contraception after medical abortion between January 2007 and June 2009. Main outcome measures were numbers of women referred, attendance rates, interval to insertion, devices chosen and known complication rates. RESULTS: Of the 237 women referred, 126 (53%) attended for intrauterine contraception insertion. Attenders were slightly but significantly older than non-attenders (mean ages of 30 and 27 years, respectively; p=0.003), less likely to live in an area of deprivation (p=0.045) and were significantly more likely to have attended the FPC in the past (p<0.0001). Most attenders (90%; n=113) proceeded to have an intrauterine method inserted; 57% (n=64) chose the levonorgestrel intrauterine system and 43% (n=49) chose a copper intrauterine device. The median interval to insertion was 21 (range 0-54) days. Of those women (n=55) who attended for routine follow-up 6 weeks later (49%), there were four (7.2%) cases of expulsion, two (3.6%) requests for removal and four (7.2%) cases of suspected infection. CONCLUSIONS: Only half the women fast-tracked for intrauterine contraception actually attended and these tended to be women who were pre-existing clients of the FPC. Consideration should therefore be given to provision of immediate insertion where possible. PMID- 22294786 TI - CCL11 elicits secretion of RNases from mouse eosinophils and their cell-free granules. AB - Rapid secretion of eosinophil-associated RNases (EARs), such as the human eosinophilic cationic protein (ECP), from intracellular granules is central to the role of eosinophils in allergic diseases and host immunity. Our knowledge regarding allergic inflammation has advanced based on mouse experimental models. However, unlike human eosinophils, capacities of mouse eosinophils to secrete granule proteins have been controversial. To study mechanisms of mouse eosinophil secretion and EAR release, we combined an RNase assay of mouse EARs with ultrastructural studies. In vitro, mouse eosinophils stimulated with the chemokine eotaxin-1 (CCL11) secreted enzymatically active EARs (EC(50) 5 nM) by piecemeal degranulation. In vivo, in a mouse model of allergic airway inflammation, increased airway eosinophil infiltration (24-fold) correlated with secretion of active RNases (3-fold). Moreover, we found that eosinophilic inflammation in mice can involve eosinophil cytolysis and release of cell-free granules. Cell-free mouse eosinophil granules expressed functional CCR3 receptors and secreted their granule proteins, including EAR and eosinophil peroxidase in response to CCL11. Collectively, these data demonstrate chemokine-dependent secretion of EARs from both intact mouse eosinophils and their cell-free granules, findings pertinent to understanding the pathogenesis of eosinophil associated diseases, in which EARs are key factors. PMID- 22294788 TI - The growing problem of antimicrobial resistance. PMID- 22294787 TI - Role of RanBP9 on amyloidogenic processing of APP and synaptic protein levels in the mouse brain. AB - We previously reported that RanBP9 binds low-density lipoprotein receptor-related protein (LRP), amyloid precursor protein (APP), and BACE1 and robustly increased Abeta generation in a variety of cell lines and primary neuronal cultures. To confirm the physiological/ pathological significance of this phenotype in vivo, we successfully generated transgenic mice overexpressing RanBP9 as well as RanBP9 null mice. Here we show that RanBP9 overexpression resulted in >2-fold increase in Abeta40 levels as early as 4 mo of age. A sustained increase in Abeta40 levels was seen at 12 mo of age in both CHAPS-soluble and formic acid (FA)-soluble brain fractions. In addition, Abeta42 levels were also significantly increased in FA soluble fractions at 12 mo of age. More important, increased Abeta levels were translated to increased deposition of amyloid plaques. In addition, RanBP9 overexpression significantly decreased the levels of synaptophysin and PSD-95 proteins. Conversely, RanBP9-null mice showed increased levels of synaptophysin, PSD-95, and drebrin A protein levels. Given that loss of synapses is the best pathological correlate of cognitive deficits in Alzheimer's disease (AD), increased Abeta levels by RanBP9 observed in the present study provides compelling evidence that RanBP9 may indeed play a key role in the etiology of AD. If so, RanBP9 provides a great opportunity to develop novel therapy for AD. PMID- 22294789 TI - An ethicist's commentary on duplicity in pet food marketing. PMID- 22294790 TI - Feline leukemia virus and feline immunodeficiency virus in Canada: recommendations for testing and management. AB - Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are common and important infectious disease agents of cats in Canada. Seroprevalence data for FeLV and FIV in various populations of Canadian cats are reviewed and recommendations for testing and management of infections by these viruses in cats in Canada are presented. Retrovirus testing in Canada is infrequent in comparison with the United States, and efforts should be focused on reducing physical and other barriers to testing, and on education of veterinarians, veterinary team members, and cat owners regarding the importance of testing. New test methodologies for FeLV and FIV are emerging, and should be independently evaluated in order to provide practitioners with information on test reliability. Finally, more information is needed on FIV subtypes in Canada to improve diagnostics and vaccines, and to provide information on disease outcomes. PMID- 22294791 TI - Evaluation of a constant rate infusion of lidocaine for balanced anesthesia in dogs undergoing surgery. AB - This study assessed the intraoperative analgesic effects of intravenous lidocaine administered by a constant rate infusion (CRI) in surgical canine patients. A prospective, blinded, randomized study was designed with 2 treatment groups: A (lidocaine) and B (placebo), involving 41 dogs. All patients were premedicated with acepromazine and buprenorphine, induced with propofol and midazolam; anesthesia was maintained with isoflurane in oxygen. Group A received 2 mg/kg IV lidocaine immediately after induction, followed within 5 min by a CRI at 50 MUg/kg/min. Group B received an equivalent volume of saline instead of lidocaine. Changes in heart rate and blood pressure during maintenance were treated by increasing CRI. Fentanyl was used as a supplemental analgesic when intraoperative nociceptive response was not controlled with the maximum dose of lidocaine infusion. There was a significantly lower use of supplemental intraoperative analgesia in the lidocaine than in the placebo group. Group B dogs had almost twice as high a risk of intraoperative nociceptive response as group A dogs. PMID- 22294792 TI - Seroepidemiology of respiratory (group 2) canine coronavirus, canine parainfluenza virus, and Bordetella bronchiseptica infections in urban dogs in a humane shelter and in rural dogs in small communities. AB - This prospective study evaluated seroepidemiologic features of canine respiratory coronavirus (CRCoV), canine parainfluenza virus (CPIV), and Bordetella bronchiseptica infections in dogs in an urban humane shelter and in rural/small community dog populations in western Canada. Seroprevalence of CRCoV and CPIV was low compared with other countries; seroprevalence of B. bronchiseptica was moderate to high in most populations examined. Rural dogs were 0.421 times (P <= 0.0001) less likely to be positive for CRCoV than dogs admitted to the shelter. There were no statistical differences in prevalence of antibodies to B. bronchiseptica and CPIV between urban and rural populations. Dogs from Fort Resolution, NWT were significantly (P < 0.05) less likely to have moderate or high antibody titers to the 3 agents than dogs in the shelter. Seroconversion to CRCoV was common in dogs in the shelter, but was not associated (P = 0.18) with respiratory disease. Antibodies to CRCoV, CPIV, or B. bronchiseptica on arrival were not significantly (P > 0.05) associated with disease-sparing after entry into the shelter. PMID- 22294793 TI - Cardiac function in dogs with chronic Chagas cardiomyopathy undergoing autologous stem cell transplantation into the coronary arteries. AB - This study assessed the effects of a single intracoronary injection of autologous stem cells on the cardiac function of dogs with Chagas cardiomyopathy. Bone marrow-derived stem cells were delivered into the right and left coronary arteries of 5 mature dogs with mildly compromised cardiac function due to chronic Chagas cardiomyopathy. Blood pressure and electrocardiographic and echocardiographic parameters were recorded at monthly intervals for 6 mo in the 3 dogs that survived. Although no changes were observed in the electrocardiogram and blood pressure, there was a significant increase in peak velocity of aortic flow 3 mo after stem cell transplantation. Pre-ejection period, isovolumic relaxation time, and the Tei index of myocardial performance were reduced significantly 4 mo after the procedure. All significant changes persisted to the end of the study. The results suggest that the transplantation of autologous bone marrow-derived stem cells into the coronary arteries of dogs with Chagas cardiomyopathy may have a beneficial effect but the small number of dogs studied was a limitation. PMID- 22294794 TI - Effects of short-term oral administration of propranolol on tear secretion in clinically normal dogs. AB - This study evaluated the effects of short-term oral administration of propranolol on tear secretion in 15 clinically normal crossbreed dogs. The treatment group (n = 8) received propranolol (2 mg/kg q8h) orally for 7 days. The control group (n = 7) received placebo during the study. Schirmer I tear tests were performed on both eyes 1 d prior to drug administration (T(0)), at 1 (T(1)), 3 (T(3)), and 7 (T(7)) days of treatment. Tear production in dogs, measured by STT, was not significantly reduced in both groups. PMID- 22294795 TI - Retrosternal (Morgagni) diaphragmatic hernia. AB - This study presents the case of a shih tzu puppy, in which a rare congenital Morgagni diaphragmatic hernia was diagnosed. The diagnosis was based on abdominal and thoracic radiographs, including a contrast study of the gastrointestinal tract, which revealed a co-existing umbilical hernia. Both hernias were repaired by surgery. PMID- 22294796 TI - Small intestinal strangulation caused by a mesodiverticular band and diverticulum on the mesenteric border of the small intestine in a horse. AB - A 4-year-old Quarter horse stallion was presented for acute abdominal pain. Exploratory celiotomy revealed a mesenteric diverticulum of the jejunum and mesodiverticular band that were associated with small intestinal strangulation. Resection and anastomosis were performed. A second celiotomy was performed due to adhesions. The horse recovered completely and returned to training. PMID- 22294797 TI - Septic peritonitis and uroperitoneum secondary to subclinical omphalitis and concurrent necrotizing cystitis in a colt. AB - A 15-day-old American Quarter horse colt was presented for depression and pyrexia. Peritonitis was diagnosed following peritoneal fluid analysis. Exploratory laparotomy revealed an area of focal necrosis over the dorsal wall of the urinary bladder leading to peritonitis and uroperitoneum. The affected area of the urinary bladder was resected and the peritonitis resolved with medical treatment. PMID- 22294798 TI - Atypical hypoadrenocorticism in a Birman cat. AB - A 1-year-old female spayed Birman cat was presented with a history of inappropriate urination and defecation, lethargy, anorexia, and weight loss. After intermittent responses to non-specific therapy she was diagnosed with atypical hypoadrenocorticism from the results of an adrenocorticotropic hormone stimulation test. PMID- 22294799 TI - The art of private veterinary practice: intellectual communication. PMID- 22294800 TI - A clinical oncology case report. PMID- 22294801 TI - An overview of dentigerous cysts in dogs and cats. PMID- 22294802 TI - Developing Early Literacy Skills: Things We Know We Know and Things We Know We Don't Know. PMID- 22294803 TI - Misunderstood statistical assumptions undermine criticism of the National Early Literacy Panel's Report. PMID- 22294804 TI - The emerging role of hypocretin (orexin-A) in the developing central nervous system. PMID- 22294805 TI - Seeking useful biomarkers for the quality and effectiveness of sleep. PMID- 22294806 TI - Insomnia research is coming of age. PMID- 22294807 TI - Maturation of heart rate and blood pressure variability during sleep in term-born infants. AB - STUDY OBJECTIVES: Abnormal blood pressure control is implicated in the sudden infant death syndrome (SIDS). However, no data exist on normal development of blood pressure control during infancy. This study assessed maturation of autonomic control of blood pressure and heart rate during sleep within the first 6 months of life. PARTICIPANTS: Term infants (n = 31) were studied longitudinally at 2-4 weeks, 2-3 months, and 5-6 months postnatal age. INTERVENTIONS: Infants underwent daytime polysomnography at each age studied. Blood pressure and heart rate were recorded during quiet (QS) and active (AS) sleep in undisturbed baseline and head-up tilt conditions. MEASUREMENTS AND RESULTS: Autonomic control was assessed using spectral indices of blood pressure and heart rate variability (BPV and HRV) in ranges of low frequency (LF, reflecting sympathetic + parasympathetic activity) and high frequency (HF, parasympathetic activity), total power (LF+HF), and LF/HF ratio (sympathovagal balance). With increasing postnatal age and predominantly during QS, HRV-LF, HRV-HF, and HRV total power increased, while HRV-LF/HF decreased. BPV-LF/HF also decreased with postnatal age. All changes were evident in both baseline and head-up tilt conditions. BPV LF and BPV total power during tilts were markedly reduced in QS versus AS at each age. CONCLUSIONS: In sleeping infants, sympathetic vascular modulation of the circulation decreases with age, while parasympathetic control of heart rate is strengthened. These normative data will aid in the early identification of conditions where autonomic function is impaired, such as in SIDS. PMID- 22294808 TI - CSF levels of hypocretin-1 (orexin-A) peak during early infancy in humans. AB - STUDY OBJECTIVES: Hypocretin (orexin) is a unique neuropeptide involved in the consolidation of wakefulness and sleep. Although hypocretin-1 levels in the cerebrospinal fluid (CSF) are stable after infancy, how levels change in preterm and term human infants is unknown. DESIGN, PATIENTS, AND SETTING: Hypocretin-1 levels were measured in CSF samples, obtained from 284 preterm (25-37 gestational weeks) and full-term infants in the first 4 months of life and 35 older children (ages 0.5-13 years), in a tertiary hospital. MEASUREMENTS AND RESULTS: Detailed clinical and laboratory data were collected for each of the 319 participants. Based on that data, 108 neurologically intact children were selected (95 infants [43 preterm and 52 term] and 13 older children). CSF hypocretin-1 was measured by direct radioimmunoassay. Hypocretin-1 levels at the first weeks of the 3rd embryonic trimester (gestational age [GA] 28-34 weeks) were 314 +/- 65 pg/mL (n = 17). The levels linearly increased during the third trimester and early infancy (r = 0.6), peaking in infants of 2-4 months ages (476 +/- 72 pg/mL; n = 16) and decreasing thereafter; hypocretin levels in 2- to 4-month-old infants were significantly higher than those in children 0.5-13 years old (353 +/- 78 pg/mL, n = 13; P = 0.0001). CONCLUSIONS: The present findings indicate that in human infants, CSF hypocretin-1 increases during the third embryonic trimester and is highest at 4 months of life. Thereafter, and consistent with previously published results, hypocretin levels are lower and stable until the geriatric age. This pattern may reflect the role of hypocretin in the dramatic process of sleep and wakefulness consolidation that occurs during early infancy. PMID- 22294809 TI - An adaptive-duration version of the PVT accurately tracks changes in psychomotor vigilance induced by sleep restriction. AB - STUDY OBJECTIVES: The Psychomotor Vigilance Test (PVT) is a widely used assay of behavioral alertness sensitive to the effects of sleep loss and circadian misalignment. The standard 10-minute duration of the PVT is often considered impractical for operational or clinical environments. Therefore, we developed and validated an adaptive-duration version of the PVT (PVT-A) that stops sampling once it has gathered enough information to correctly classify PVT performance. DESIGN: Repeated-measures experiments involving 10-minute PVT assessments every 2 hours across both acute total sleep deprivation (TSD) and 5 days of chronic partial sleep deprivation (PSD). SETTING: Controlled laboratory environment. PARTICIPANTS: Seventy-four healthy subjects (34 women), aged 22 to 45 years. INTERVENTIONS: A TSD experiment involving 33 hours awake (n = 31 subjects), and a PSD experiment involving 5 nights of 4 hours time in bed (n = 43 subjects). MEASUREMENTS AND RESULTS: The PVT-A algorithm was trained with 527 TSD test bouts and validated with 880 PSD test bouts. Based on our primary outcome measure "number of lapses (response times >= 500 ms) plus false starts (premature responses or response times < 100 ms)," 10-minute PVT performance was classified into high (<= 5 lapses and false starts), medium (> 5 and <= 16 lapses and false starts), or low (> 16 lapses and false starts). The decision threshold for PVT-A termination was set so that at least 95% of training data-set tests were classified correctly and no test was classified incorrectly across 2 performance categories (i.e., high as low or low as high), resulting in an average test duration of 6.0 minutes (SD 2.4 min). In the validation data set, 95.7% of test bouts were correctly classified, and there were no incorrect classifications across 2 categories. Agreement corrected for chance was excellent (kappa = 0.92). Across the 3 performance categories, sensitivity averaged 93.7% (range 87.2% 100%), and specificity averaged 96.8% (range 91.6%-99.9%). Test duration averaged 6.4 minutes (SD 1.7 min), with a minimum of 27 seconds. CONCLUSIONS: We developed and validated a highly accurate, sensitive, and specific adaptive-duration version of the 10-minute PVT. Test duration of the adaptive PVT averaged less than 6.5 minutes, with 60 tests (4.3%) terminating after less than 2 minutes, increasing the practicability of the test in operational and clinical settings. The adaptive-duration strategy may be superior to a simple reduction of PVT duration in which the fixed test duration may be too short to identify subjects with moderate impairment (showing deficits only later during the test) but unnecessarily long for those who are either fully alert or severely impaired. PMID- 22294810 TI - Respiratory cycle-related EEG changes: response to CPAP. AB - STUDY OBJECTIVES: Respiratory cycle-related EEG changes (RCREC) quantify statistically significant synchrony between respiratory cycles and EEG spectral power, vary to some extent with work of breathing, and may help to predict sleepiness in patients with obstructive sleep apnea. This study was designed to assess the acute response of RCREC to relief of upper airway obstruction by positive airway pressure (PAP). DESIGN: Comparison of RCREC between baseline diagnostic polysomnograms and PAP titration studies. SETTING: Accredited academic sleep disorders center. PATIENTS: Fifty adults referred for suspected sleep disordered breathing. INTERVENTIONS: For each recording, the RCREC in specific physiologic EEG frequency ranges were computed as previously described for the last 3 h of sleep not occupied by apneic events. RESULTS: The sample included 27 women; mean age was 47 +/- 11 (SD) years; and median respiratory disturbance index at baseline was 24 (inter-quartile range 15-43). Decrements in RCREC, from baseline to PAP titration, reached 43%, 24%, 14%, 22%, and 31% for delta (P = 0.0004), theta (P = 0.01), alpha (P = 0.10), sigma (P = 0.08), and beta (P = 0.01) EEG frequency ranges, respectively. Within each specific sleep stage, these reductions from baseline to PAP studies in synchrony between EEG power and respiratory cycles still reached significance (P < 0.05) for one or more EEG frequency ranges and for all frequency ranges during REM sleep. CONCLUSIONS: RCREC tends to diminish acutely with alleviation of upper airway obstruction by PAP. These data in combination with previous observations support the hypothesis that RCREC reflect numerous, subtle, brief, but consequential inspiratory microarousals. PMID- 22294811 TI - Switch-task performance in rats is disturbed by 12 h of sleep deprivation but not by 12 h of sleep fragmentation. AB - STUDY OBJECTIVES: Task-switching is an executive function involving the prefrontal cortex. Switching temporarily attenuates the speed and/or accuracy of performance, phenomena referred to as switch costs. In accordance with the idea that prefrontal function is particularly sensitive to sleep loss, switch-costs increase during prolonged waking in humans. It has been difficult to investigate the underlying neurobiological mechanisms because of the lack of a suitable animal model. Here, we introduce the first switch-task for rats and report the effects of sleep deprivation and inactivation of the medial prefrontal cortex. DESIGN: Rats were trained to repeatedly switch between 2 stimulus-response associations, indicated by the presentation of a visual or an auditory stimulus. These stimulus-response associations were offered in blocks, and performance was compared for the first and fifth trials of each block. Performance was tested after exposure to 12 h of total sleep deprivation, sleep fragmentation, and their respective movement control conditions. Finally, it was tested after pharmacological inactivation of the medial prefrontal cortex. SETTINGS: Controlled laboratory settings. PARTICIPANTS: 15 male Wistar rats. MEASUREMENTS & RESULTS: Both accuracy and latency showed switch-costs at baseline. Twelve hours of total sleep deprivation, but not sleep fragmentation, impaired accuracy selectively on the switch-trials. Inactivation of the medial prefrontal cortex by local neuronal inactivation resulted in an overall decrease in accuracy. CONCLUSIONS: We developed and validated a switch-task that is sensitive to sleep deprivation. This introduces the possibility for in-depth investigations on the neurobiological mechanisms underlying executive impairments after sleep disturbance in a rat model. PMID- 22294812 TI - Free recall of word lists under total sleep deprivation and after recovery sleep. AB - STUDY OBJECTIVES: One task that has been used to assess memory effects of prior total sleep deprivation (TSD) is the immediate free recall of word lists; however, results have been mixed. A possible explanation for this is task impurity, since recall of words from different serial positions reflects use of distinct types of memory (last words: short-term memory; first and intermediate words: episodic memory). Here we studied the effects of 2 nights of TSD on immediate free recall of semantically unrelated word lists considering the serial position curve. DESIGN: Random allocation to a 2-night TSD protocol followed by one night of recovery sleep or to a control group. SETTING: Study conducted under continuous behavioral monitoring. PARTICIPANTS: 24 young, healthy male volunteers. INTERVENTION: 2 nights of total sleep deprivation (TSD) and one night of recovery sleep. MEASUREMENTS AND RESULTS: Participants were shown five 15 unrelated word-lists at baseline, after one and 2 nights of TSD, and after one night of recovery sleep. We also investigated the development of recall strategies (learning) and susceptibility to interference from previous lists. No free recall impairment occurred during TSD, irrespective of serial position. Interference was unchanged. Both groups developed recall strategies, but task learning occurred earlier in controls and was evident in the TSD group only after sleep recovery. CONCLUSION: Prior TSD spared episodic memory, short-term phonological memory, and interference, allowed the development of recall strategies, but may have decreased the advantage of using these strategies, which returned to normal after recovery sleep. PMID- 22294813 TI - Glucose tolerance in patients with narcolepsy. AB - STUDY OBJECTIVES: Obesity is a common feature of narcolepsy. In addition, an increased occurrence of non-insulin dependent diabetes has been reported. So far, it is not known whether glucose metabolism in narcolepsy is disturbed due to, or independently of obesity. DESIGN: Case-control study. SETTING: Sleep medicine clinic at a research institute. PATIENTS: We studied 17 patients with narcolepsy/cataplexy compared to 17 healthy controls matched for age, sex, and body mass index (BMI). INTERVENTIONS: A 75-g oral glucose tolerance test was performed. MEASUREMENTS: Glucose tolerance was determined by computing plasma glucose curve following oral glucose challenge for 240 minutes; insulin sensitivity and insulin secretion by homeostasis model assessment and minimal model analysis. RESULTS: Standard outcome measures and indices of the oral glucose tolerance test did not differ between the patient group and the group of control subjects. CONCLUSIONS: In this study, no clinically relevant pathologic findings in the glucose metabolism of narcoleptic patients compared to weight matched controls were found. Thus, narcolepsy is unlikely to be a risk factor per se for impaired glucose tolerance or diabetes. PMID- 22294814 TI - The longitudinal relationship between fatigue and sleep in breast cancer patients undergoing chemotherapy. AB - STUDY OBJECTIVE: Fatigue and sleep disturbances are two of the most common and distressing symptoms of cancer patients. A relationship between the two symptoms was reported in symptom cluster studies; however, only subjective measurements of sleep were examined and most studies were cross-sectional. In this study of women with breast cancer undergoing chemotherapy, we explored the longitudinal relationship between fatigue and sleep measured both subjectively and objectively. DESIGN: Prospective study. Data were collected at 7 time points: before (baseline) and during the 3 weeks of cycle 1 and cycle 4 chemotherapy. PARTICIPANTS: Ninety-seven women with newly diagnosed stage I-III breast cancer who were scheduled to receive at least four 3-week cycles of chemotherapy. MEASUREMENT AND RESULTS: Objective sleep parameters were measured with an Actillume actigraph (Ambulatory Monitoring Inc.). Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). Fatigue was assessed with the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). Fatigue became worse during both cycles of chemotherapy (P-values < 0.01). Subjective sleep quality was poor at baseline and remained unchanged throughout treatment. Objective nighttime and daytime total sleep time increased compared to baseline during the treatment administration week of both cycles; daytime total wake time decreased during the treatment week of both cycles and during the last 2 week of cycle 4. Mixed model results revealed that fatigue was positively associated with total PSQI scores and with objective measures of total nap time, and negatively associated with total wake time during the day (all P-values < 0.01). CONCLUSION: Fatigue was significantly associated with subjective reports of poor sleep and objective measures of daytime sleepiness, but not with nocturnal sleep as measured with actigraphy. This relationship between fatigue and sleep warrants further studies to explore their possible common underlying etiology. PMID- 22294815 TI - Sleep in spousal Alzheimer caregivers: a longitudinal study with a focus on the effects of major patient transitions on sleep. AB - STUDY OBJECTIVES: Findings on sleep disturbances in family dementia caregivers are conflicting. We studied the longitudinal effects of dementia caregiving and major transitions in the caregiving situation on caregivers' sleep and the effect of moderating variables. DESIGN AND SETTING: Community-based longitudinal study with assessments about once a year for up to three years. PARTICIPANTS: A sample of 109 elderly spousal Alzheimer caregivers and 48 non-caregiving age- and gender matched controls. MEASUREMENTS AND RESULTS: Random regression models with fixed and time-variant effects for covariates known to affect sleep were used to evaluate changes in the Pittsburgh Sleep Quality Index (PSQI) and in four actigraphy measures over time in relation to caregiving status and transitions (i.e., nursing home placement or death of the Alzheimer disease spouse). Multivariate-adjusted sleep characteristics did not significantly differ between caregivers and non-caregivers over time. Spousal death increased caregivers' nighttime wake after sleep onset (WASO) by 23 min (P = 0.002) and daytime total sleep time (TST) by 29 min (P = 0.003), while nighttime sleep percent decreased by 3.2% (P = 0.009) and nighttime TST did not change. Placement of the spouse had no significant effect on caregivers' sleep. Older age, male gender, role overload, depressive symptoms, and proinflammatory cytokines variously emerged as significant moderators of the relationships between caregiving and transitions with poor subjective and objective sleep. CONCLUSIONS: Alzheimer caregivers and non-caregiving controls had similar trajectories of sleep. However, there may be subgroups of caregivers who are vulnerable to develop sleep disturbances, including those whose spouses have died. PMID- 22294816 TI - Daily sleep and fatigue characteristics in nulliparous women during the third trimester of pregnancy. AB - OBJECTIVES: To examine the association among nighttime sleep and daytime napping behaviors, depressive symptoms, and perception of fatigue in pregnant women. DESIGN: A prospective descriptive study with within-subject design. SETTING: A university-affiliated hospital and participants' home environments. PARTICIPANTS: Thirty-eight third trimester nulliparous women completed sleep and depressive symptom questionnaires, wore a wrist actigraphy monitor for 7 consecutive days, and kept a concurrent diary reporting naps and rating their level of fatigue using a 0-10 visual analogue scale each morning, midday, afternoon, and evening. A generalized estimating equation regression model was applied to evaluate the time-dependent association. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Mean duration of total nighttime sleep by actigraphy was 386.3 +/- 60.7 min, with 11 (28.9%) women having an average total nighttime sleep < 6 h. Nineteen women (50%) napped > 3 days, and only 2 women did not nap over the entire week. Antecedent night sleep duration had a significant inverse association with morning (P = 0.022) and afternoon fatigue (P = 0.009) of the subsequent day. Self-reported naps were significantly associated with midday fatigue (P = 0.003). More depressive symptoms predicted more severe fatigue throughout the day. CONCLUSIONS: Results suggest that interventions designed to increase sleep duration and decrease depressive symptoms have the potential to prevent, ameliorate, or reduce fatigue in pregnant women. Depressive symptoms during pregnancy likely share some psychological and behavioral tendencies with fatigue and/or sleep disturbance which may complicate the evaluation of intervention effect. PMID- 22294817 TI - The supraglottic effect of a reduction in expiratory mask pressure during continuous positive airway pressure. AB - STUDY OBJECTIVES: Patients with obstructive sleep apnea may have difficulty exhaling against positive pressure, hence limiting their acceptance of continuous positive airway pressure (CPAP). C-Flex is designed to improve comfort by reducing pressure in the mask during expiration proportionally to expiratory airflow (3 settings correspond to increasing pressure changes). When patients use CPAP, nasal resistance determines how much higher supraglottic pressure is than mask pressure. We hypothesized that increased nasal resistance results in increased expiratory supraglottic pressure swings that could be mitigated by the effects of C-Flex on mask pressure. DESIGN: Cohort study. SETTING: Sleep center. PARTICIPANTS: Seventeen patients with obstructive sleep apnea/hypopnea syndrome and a mechanical model of the upper airway. INTERVENTIONS: In patients on fixed CPAP, CPAP with different C-Flex levels was applied multiple times during the night. In the model, 2 different respiratory patterns and resistances were tested. MEASUREMENTS AND RESULTS: Airflow, expiratory mask, and supraglottic pressures were measured on CPAP and on C-Flex. Swings in pressure during expiration were determined. On CPAP, higher nasal resistance produced greater expiratory pressure swings in the supraglottis in the patients and in the model, as expected. C-Flex 3 produced expiratory drops in mask pressure (range -0.03 to 2.49 cm H(2)O) but mitigated the expiratory pressure rise in the supraglottis only during a sinusoidal respiratory pattern in the model. CONCLUSIONS: Expiratory changes in mask pressure induced by C-Flex did not uniformly transmit to the supraglottis in either patients with obstructive sleep apnea on CPAP or in a mechanical model of the upper airway with fixed resistance. Data suggest that the observed lack of expiratory drop in supraglottic pressure swings is related to dynamics of the C-Flex algorithm. PMID- 22294818 TI - Effects of a 3-hour sleep delay on sleep homeostasis in alcohol dependent adults. AB - OBJECTIVES: This study evaluated slow wave activity homeostatic response to a mild sleep challenge in alcohol-dependent adults compared to healthy controls. DESIGN: Participants maintained a 23:00-06:00 schedule for 5 days verified by actigraphy and diary, followed by 3 nights in the lab: adaptation, baseline, and a sleep delay night with an 02:00-09:00 schedule. SETTING: Sleep ' Chronophysiology laboratory. PARTICIPANTS: 48 alcohol-dependent adults (39 men, 9 women) who were abstinent for at least 3 weeks and 16 healthy control adults (13 men, 3 women), 21-55 years of age participated in study. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Slow wave EEG activity (SWA) in consecutive NREM periods was compared between baseline and sleep delay nights and between AD and HC groups, using age and sex as statistical covariates. The AD group showed a blunted SWA response to sleep delay with significantly lower SWA power than the HC group. Exponential regression analyses confirmed lower asymptotic SWA with a slower decay rate over NREM sleep time in the AD group. Results were similar for raw SWA and %SWA on the delay night expressed relative to baseline SWA. CONCLUSIONS: Alcohol dependence is associated with impaired SWA regulation and a blunted response to a mild homeostatic sleep challenge. PMID- 22294819 TI - A closed literature-based discovery technique finds a mechanistic link between hypogonadism and diminished sleep quality in aging men. AB - STUDY OBJECTIVES: Sleep quality commonly diminishes with age, and, further, aging men often exhibit a wider range of sleep pathologies than women. We used a freely available, web-based discovery technique (Semantic MEDLINE) supported by semantic relationships to automatically extract information from MEDLINE titles and abstracts. DESIGN: We assumed that testosterone is associated with sleep (the A-C relationship in the paradigm) and looked for a mechanism to explain this association (B explanatory link) as a potential or partial mechanism underpinning the etiology of eroded sleep quality in aging men. MEASUREMENTS AND RESULTS: Review of full-text papers in critical nodes discovered in this manner resulted in the proposal that testosterone enhances sleep by inhibiting cortisol. Using this discovery method, we posit, and could confirm as a novel hypothesis, cortisol as part of a mechanistic link elucidating the observed correlation between decreased testosterone in aging men and diminished sleep quality. CONCLUSIONS: This approach is publically available and useful not only in this manner but also to generate from the literature alternative explanatory models for observed experimental results. PMID- 22294820 TI - The consensus sleep diary: standardizing prospective sleep self-monitoring. AB - STUDY OBJECTIVES: To present an expert consensus, standardized, patient-informed sleep diary. METHODS AND RESULTS: Sleep diaries from the original expert panel of 25 attendees of the Pittsburgh Assessment Conference(1) were collected and reviewed. A smaller subset of experts formed a committee and reviewed the compiled diaries. Items deemed essential were included in a Core sleep diary, and those deemed optional were retained for an expanded diary. Secondly, optional items would be available in other versions. A draft of the Core and optional versions along with a feedback questionnaire were sent to members of the Pittsburgh Assessment Conference. The feedback from the group was integrated and the diary drafts were subjected to 6 focus groups composed of good sleepers, people with insomnia, and people with sleep apnea. The data were summarized into themes and changes to the drafts were made in response to the focus groups. The resultant draft was evaluated by another focus group and subjected to lexile analyses. The lexile analyses suggested that the Core diary instructions are at a sixth-grade reading level and the Core diary was written at a third-grade reading level. CONCLUSIONS: The Consensus Sleep Diary was the result of collaborations with insomnia experts and potential users. The adoption of a standard sleep diary for insomnia will facilitate comparisons across studies and advance the field. The proposed diary is intended as a living document which still needs to be tested, refined, and validated. PMID- 22294822 TI - Risk of post-operative complications associated with anti-TNF therapy in inflammatory bowel disease. AB - There have been increasing concerns regarding the safety of perioperative anti tumour necrosis factor (anti-TNF) alpha agents. We performed a literature review to evaluate the post-operative complications associated with perioperative anti TNF use in patients with inflammatory bowel disease. A comprehensive review was performed with a literature search utilizing Pub Med, Cochrane, OVID and EMBASE databases according to published guidelines. To date, there are only data for infliximab. There are three published studies which have assessed post-operative complications with perioperative infliximab use in patients with Crohn's disease (CD), four studies in ulcerative colitis (UC) patients, and one study on both CD and UC patients. Two out of the three studies in CD patients showed no increased post-operative complications associated with perioperative infliximab. Two out of four studies in UC patients also did not show an increase in post-operative complications, and the combined study with CD and UC patients did not show an increased risk as well. Study results could not be combined secondary to significant differences in study designs, patient population and definition of their endpoints. There appears to be a risk of post-operative complications associated with TNF therapy in some patients. Based on these data, careful patient selection and prospective data collection should be performed. PMID- 22294823 TI - Enhanced recovery for non-colorectal surgery. AB - In recent years the advent of programs for enhanced recovery after major surgery (ERAS) has led to modifications of long-standing and well-established perioperative treatments. These programs are used to target factors that have been shown to delay postoperative recovery (pain, gut dysfunction, immobility) and combine a series of interventions to reduce perioperative stress and organ dysfunction. With due differences, the programs of enhanced recovery are generally based on the preoperative amelioration of the patient's clinical conditions with whom they present for the operation, on the intraoperative and postoperative avoidance of medications that could slow the resumption of physiological activities, and on the promotion of positive habits in the early postoperative period. Most of the studies were conducted on elective patients undergoing colorectal procedures (either laparotomic or laparoscopic surgery). Results showed that ERAS protocols significantly improved the lung function and reduced the time to resumption of oral diet, mobilization and passage of stool, hospital stay and return to normal activities. ERAS' acceptance is spreading quickly among major centers, as well as district hospitals. With this in mind, is there also a role for ERAS in non-colorectal operations? PMID- 22294824 TI - Hepatitis C virus induced insulin resistance impairs response to anti viral therapy. AB - Hepatitis C virus (HCV) infection is an important risk factor for insulin resistance (IR). The latter is the pathogenic foundation underlying metabolic syndrome, steatosis and cirrhosis, and possibly hepatocellular carcinoma (HCC). The interplay between genetic and environmental risk factors ultimately leads to the development of IR. Obesity is considered a major risk factor, with dysregulation of levels of secreted adipokines from distended adipose tissue playing a major role in IR. HCV-induced IR may be due to the HCV core protein inducing proteasomal degradation of insulin receptor substrates 1 and 2, blocking intracellular insulin signaling. The latter is mediated by increased levels of both tumour necrosis factor-alpha (TNF-alpha) and suppressor of cytokine signaling 3 (SOC-3). IR, through different mechanisms, plays a role in the development of steatosis and its progression to steatohepatitis, cirrhosis and even HCC. In addition, IR has a role in impairing TNF signaling cascade, which in turn blocks STAT-1 translocation and interferon stimulated genes production avoiding the antiviral effect of interferon. PMID- 22294825 TI - Stress-induced visceral analgesia assessed non-invasively in rats is enhanced by prebiotic diet. AB - AIM: To investigate the influence of repeated water avoidance stress (rWAS) on the visceromotor response (VMR) to colorectal distension (CRD) and the modulation of the response by a prebiotic diet in rats using a novel surgery-free method of solid-state manometry. METHODS: Male Wistar rats fed a standard diet with or without 4% enzyme-treated rice fiber (ERF) for 5 wk were subjected to rWAS (1 h daily x 10 d) or no stress. The VMR to graded phasic CRD was assessed by intraluminal colonic pressure recording on days 0 (baseline), 1 and 10 (45 min) and 11 (24 h) after rWAS and expressed as percentage change from baseline. Cecal content of short chain fatty acids and distal colonic histology were assessed on day 11. RESULTS: WAS on day 1 reduced the VMR to CRD at 40 and 60 mmHg similarly by 28.9% +/- 6.6% in both diet groups. On day 10, rWAS-induced reduction of VMR occurred only at 40 mmHg in the standard diet group (36.2% +/- 17.8%) while in the ERF group VMR was lowered at 20, 40 and 60 mmHg by 64.9% +/- 20.9%, 49.3% +/- 11.6% and 38.9% +/- 7.3% respectively. The visceral analgesia was still observed on day 11 in ERF- but not in standard diet-fed rats. By contrast the non-stressed groups (standard or ERF diet) exhibited no changes in VMR to CRD. In standard diet-fed rats, rWAS induced mild colonic histological changes that were absent in ERF-fed rats exposed to stress compared to non-stressed rats. The reduction of cecal content of isobutyrate and total butyrate, but not butyrate alone, was correlated with lower visceral pain response. Additionally, ERF diet increased rWAS-induced defecation by 26% and 75% during the first 0-15 min and last 15-60 min, respectively, compared to standard diet, and reduced rats' body weight gain by 1.3 fold independently of their stress status. CONCLUSION: These data provide the first evidence of psychological stress-related visceral analgesia in rats that was enhanced by chronic intake of ERF prebiotic. PMID- 22294826 TI - Aging is a risk factor of nonalcoholic fatty liver disease in premenopausal women. AB - AIM: To clarify the relationship between age, menopause, and nonalcoholic fatty liver disease (NAFLD) in women. METHODS: We conducted a follow-up study on nonalcoholic fatty liver disease by using abdominal ultrasonography, and investigated the relationship of age and menopause with the development of NAFLD in women. We followed 1829 women and 2572 men (response rate, 86%) selected in 2001 to represent the non-institutionalized adult population of Gifu, Japan. Data collected included self-reported medical history, lifestyle factors, and menopausal status. The postmenopausal state was defined as beginning 1 year after the cessation of menses. We diagnosed NAFLD with the aid of abdominal ultrasonography by using diagnostic criteria described previously. RESULTS: The prevalence of NAFLD in women increases with age, but does not alter with age in men. Furthermore, the prevalence of NAFLD in premenopausal women (6%) was lower than that in men (24%) and in postmenopausal women (15%). The associations of the postmenopausal state and hormone replacement therapy with NAFLD were statistically significant in a univariate logistic regression model. At the follow-up examination, 67 women (5%) were newly diagnosed with NAFLD. The incidence of NAFLD was 3.5% (28/802) in premenopausal women, 7.5% (4/53) in menopausal women, 6.1% (24/392) in postmenopausal women, and 5.3% (11/206) in women receiving hormone replacement therapy. The weight gain in premenopausal women was equal to that in postmenopausal women. Metabolic syndrome and weight gain were independent risk factors for NAFLD in pre- and postmenopausal women, but age was an independent risk factor in premenopausal women only. CONCLUSION: Aging is a risk factor for NAFLD in premenopausal women, independent of weight gain or influence of metabolic syndrome. PMID- 22294827 TI - High level of urokinase plasminogen activator contributes to cholangiocarcinoma invasion and metastasis. AB - AIM: To investigate the role of urokinase plasminogen activator (uPA) in cholangiocarcinoma (CCA) invasion and its correlation with clinicopathological parameters. METHODS: uPA expression in CCA tissue was determined by immunohistochemistry. The level of uPA from two CCA cell lines (HuCCA-1 and KKU M213) and a non-cancer immortalized cholangiocyte cell line (H69) was monitored by plasminogen-gelatin zymography and western blotting, whereas that of plasminogen activator inhibitor type 1 (PAI-1) protein and uPA receptor (uPAR) mRNA was monitored by western blotting and quantitative real-time reverse transcriptase polymerase chain reaction, respectively. Two independent methods were employed to suppress uPA function: a synthetic uPA inhibitor (B428) and silencing of uPA gene expression using siRNA. In vitro invasion of the uPA disrupted cells was assessed by Matrigel-coated Transwell assay. RESULTS: The immunohistochemical study showed that 75.3% (131/174) of CCA tissues expressed uPA. High uPA expression was correlated with lymphatic invasion and metastasis of CCA patients. Plasminogen-gelatin zymography of the conditioned media and cell surface eluates showed that both CCA cell lines, but not H69, expressed both secreted and membrane-bound forms of uPA. Although the two CCA cell lines, HuCCA 1 and KKU-M213, expressed a relatively high level of uPA and uPAR, the latter exhibited a much lower degree of in vitro invasiveness, correlating with a high expression of PAI-1 in the latter, but not in the former. Suppressing uPA function with a specific uPA inhibitor, B428, or with siRNA against uPA reduced in vitro invasiveness of KKU-M213 cells, demonstrating the requirement for uPA in the invasiveness of CCA cells. Therefore, our in vivo and in vitro studies suggest that uPA is an important requirement for the invasion process of CCA. CONCLUSION: uPA expression correlates with lymphatic invasion and metastasis in vivo and is required for CCA cell invasion in vitro, suggesting its potential as a therapeutic target. PMID- 22294828 TI - Roux-en-Y reconstruction does not require gastric decompression after radical distal gastrectomy. AB - AIM: To determine whether routine nasogastric (NG) decompression benefitted patients undergoing radical gastric surgery. METHODS: Between January 1998 and December 2008, 519 patients who underwent distal gastrectomy for gastric cancer were retrospectively divided into 2 time-period cohorts; those treated with Billroth II (BII) reconstruction in the first 6 years and those with Roux-en-Y (RY) reconstruction in the last 5 years. In the latter group, the patients were further divided into 2 subgroups; with and without nasogastric decompression. RESULTS: Postoperatively, there were no significant differences in the number of anastomotic leaks between the 3 groups. In the tubeless RY group, time to semi liquid diet was significantly shorter than in the other 2 groups (4.4 d +/- 1.4 d vs 7.2 d +/- 1.3 d and 5.9 d +/- 1.2 d, P = 0.005). The length of postoperative stay was significantly increased in patients with BII reconstruction compared with patients with RY reconstruction with/without NG decompression (15.4 d +/- 4.3 d in BIIgroup vs 12.6 d +/- 3.1 d in decompressed RY and 11.4 d +/- 3.4 d in the tubeless RY group, P = 0.035). The postoperative pneumonia rate was lowest in the tubeless group and highest in the BII group (1.4% vs 4.6%, P = 0.01). Severe sore throat was noted in 59 (20.7%) members of the BII group, 18 (17.4%) members of the decompressed RY group and 6 (4.2%) members of the tubeless RY group. Fewer patients in the tubeless group complained of severe sore throat (P = 0.001). CONCLUSION: This study provides support for abandoning routine NG decompression in patients undergoing subtotal gastrectomy with Roux-en-Y gastrojejunostomy. PMID- 22294829 TI - Microencapsulated tumor assay: evaluation of the nude mouse model of pancreatic cancer. AB - AIM: To establish a more stable and accurate nude mouse model of pancreatic cancer using cancer cell microencapsulation. METHODS: The assay is based on microencapsulation technology, wherein human tumor cells are encapsulated in small microcapsules (approximately 420 MUm in diameter) constructed of semipermeable membranes. We implemented two kinds of subcutaneous implantation models in nude mice using the injection of single tumor cells and encapsulated pancreatic tumor cells. The size of subcutaneously implanted tumors was observed on a weekly basis using two methods, and growth curves were generated from these data. The growth and metastasis of orthotopically injected single tumor cells and encapsulated pancreatic tumor cells were evaluated at four and eight weeks postimplantation by positron emission tomography-computed tomography scan and necropsy. The pancreatic tumor samples obtained from each method were then sent for pathological examination. We evaluated differences in the rates of tumor incidence and the presence of metastasis and variations in tumor volume and tumor weight in the cancer microcapsules vs single-cell suspensions. RESULTS: Sequential in vitro observations of the microcapsules showed that the cancer cells in microcapsules proliferated well and formed spheroids at days 4 to 6. Further in vitro culture resulted in bursting of the membrane of the microcapsules and cells deviated outward and continued to grow in flasks. The optimum injection time was found to be 5 d after tumor encapsulation. In the subcutaneous implantation model, there were no significant differences in terms of tumor volume between the encapsulated pancreatic tumor cells and cells alone and rate of tumor incidence. There was a significant difference in the rate of successful implantation between the cancer cell microencapsulation group and the single tumor-cell suspension group (100% vs 71.43%, respectively, P = 0.0489) in the orthotropic implantation model. The former method displayed an obvious advantage in tumor mass (4th wk: 0.0461 +/- 0.0399 vs 0.0313 +/- 0.021, t = 0.81, P = 0.4379; 8th wk: 0.1284 +/- 0.0284 vs 0.0943 +/- 0.0571, t = -2.28, respectively, P = 0.0457) compared with the latter in the orthotopic implantation model. CONCLUSION: Encapsulation of pancreatic tumor cells is a reliable method for establishing a pancreatic tumor animal model. PMID- 22294830 TI - Comparative quantification of human intestinal bacteria based on cPCR and LDR/LCR. AB - AIM: To establish a multiple detection method based on comparative polymerase chain reaction (cPCR) and ligase detection reaction (LDR)/ligase chain reaction (LCR) to quantify the intestinal bacterial components. METHODS: Comparative quantification of 16S rDNAs from different intestinal bacterial components was used to quantify multiple intestinal bacteria. The 16S rDNAs of different bacteria were amplified simultaneously by cPCR. The LDR/LCR was examined to actualize the genotyping and quantification. Two beneficial (Bifidobacterium, Lactobacillus) and three conditionally pathogenic bacteria (Enterococcus, Enterobacterium and Eubacterium) were used in this detection. With cloned standard bacterial 16S rDNAs, standard curves were prepared to validate the quantitative relations between the ratio of original concentrations of two templates and the ratio of the fluorescence signals of their final ligation products. The internal controls were added to monitor the whole detection flow. The quantity ratio between two bacteria was tested. RESULTS: cPCR and LDR revealed obvious linear correlations with standard DNAs, but cPCR and LCR did not. In the sample test, the distributions of the quantity ratio between each two bacterial species were obtained. There were significant differences among these distributions in the total samples. But these distributions of quantity ratio of each two bacteria remained stable among groups divided by age or sex. CONCLUSION: The detection method in this study can be used to conduct multiple intestinal bacteria genotyping and quantification, and to monitor the human intestinal health status as well. PMID- 22294831 TI - Efficacy of intraductal ultrasonography in the diagnosis of non-opaque choledocholith. AB - AIM: To evaluate the efficacy of intraductal ultrasonography (IDUS) in the diagnosis of non-opaque, common bile duct stones. METHODS: A total of 183 patients (102 males, mean age 73 years; 81 females, mean age 70 years) with suspected common bile duct stones diagnosed through abdominal computed tomography (CT), magnetic resonance imaging (MRI), and abdominal Type-B ultrasound were included in the study. The diagnosis was confirmed through endoscopic retrograde cholangiopancreatography (ERCP) followed by IDUS. RESULTS: A total of 183 patients with suspected common bile duct (CBD) stones were included in the study as follows: 36 patients with high-density CBD stones, 68 patients with sand-like stones, 44 patients with low-density stones, 21 patients with ampullary cancer, and 14 patients with pancreatic cancer. Conventional imaging revealed 124 cases of choledochectasia, and only 36 cases of suspected CBD stones; ERCP revealed 145 cases of CBD stones with three missed diagnoses. IDUS revealed 148 cases of CBD stones, 21 cases of ampullary tumors, and 14 cases of pancreatic cancer. CONCLUSION: IDUS was more effective in the diagnosis of bile duct stones than ERCP, upper abdominal CT or upper abdominal MRI. PMID- 22294832 TI - Present and future of prophylactic antibiotics for severe acute pancreatitis. AB - AIM: To investigate the role of prophylactic antibiotics in the reduction of mortality of severe acute pancreatitis (SAP) patients, which is highly questioned by more and more randomized controlled trials (RCTs) and meta-analyses. METHODS: An updated meta-analysis was performed. RCTs comparing prophylactic antibiotics for SAP with control or placebo were included for meta-analysis. The mortality outcomes were pooled for estimation, and re-pooled estimation was performed by the sensitivity analysis of an ideal large-scale RCT. RESULTS: Currently available 11 RCTs were included. Subgroup analysis showed that there was significant reduction of mortality rate in the period before 2000, while no significant reduction in the period from 2000 [Risk Ratio, (RR) = 1.01, P = 0.98]. Funnel plot indicated that there might be apparent publication bias in the period before 2000. Sensitivity analysis showed that the RR of mortality rate ranged from 0.77 to 1.00 with a relatively narrow confidence interval (P < 0.05). However, the number needed to treat having a minor lower limit of the range (7 5096 patients) implied that certain SAP patients could still potentially prevent death by antibiotic prophylaxis. CONCLUSION: Current evidences do not support prophylactic antibiotics as a routine treatment for SAP, but the potentially benefited sub-population requires further investigations. PMID- 22294833 TI - 1H NMR-based serum metabolic profiling in compensated and decompensated cirrhosis. AB - AIM: To study the metabolic profiling of serum samples from compensated and decompensated cirrhosis patients. METHODS: A pilot metabolic profiling study was conducted using three groups: compensated cirrhosis patients (n = 30), decompensated cirrhosis patients (n = 30) and healthy controls (n = 30). A 1H nuclear magnetic resonance (NMR)-based metabonomics approach was used to obtain the serum metabolic profiles of the samples. The acquired data were processed by multivariate principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA). RESULTS: The OPLS-DA model was capable of distinguishing between decompensated and compensated cirrhosis patients, with an R2Y of 0.784 and a Q2Y of 0.598. Twelve metabolites, such as pyruvate, phenylalanine and succinate, were identified as the most influential factors for the difference between the two groups. The validation of the diagnosis prediction showed that the accuracy of the OPLS-DA model was 85% (17/20). CONCLUSION: 1H NMR spectra combined with pattern recognition analysis techniques offer a new way to diagnose compensated and decompensated cirrhosis in the future. PMID- 22294834 TI - Endoscopic submucosal dissection for large laterally spreading tumors involving the ileocecal valve and terminal ileum. AB - Endoscopic submucosal dissection is a challenging technique that enables en-bloc resection for large colorectal tumors, as laterally spreading tumors, particularly difficult, if the ileocecal valve and terminal ileum is involved. Herein, we report on one of 4 cases. The procedures, using a bipolar needle knife (B-Knife) to reduce the perforation risk and carbon dioxide instead of conventional air insufflation for patient comfort, achieved curative resections without any complications. PMID- 22294835 TI - Physiological and pathological role of local and immigrating colonic stem cells. AB - The latest avenue of research is revealing the existence of and role for the colonic stem cells in the physiological renewal of the mucosa and in pathological circumstances where they have both positive and negative effects. In the case of human colon, different levels of stem cell compartments exist. First, the crypt epithelial stem cells, which have a role in the normal crypt epithelial cell dynamics and in colorectal carcinogenesis. Close to the crypts, the second layer of stem cells can be found; the local subepithelial stem cell niche, including the pericryptic subepithelial myofibroblasts that regulate the epithelial cell differentiation and have a crucial role in cancer progression and chronic inflammation-related fibrosis. The third level of stem cell compartment is the immigrating bone-marrow-derived stem cells, which have an important role in wound healing after severe mucosal inflammation, but are also involved in cancer invasion. This paper focuses on stem cell biology in the context of physiological and pathological processes in the human colon. PMID- 22294836 TI - 8-Hydroxydeoxyguanosine: not mere biomarker for oxidative stress, but remedy for oxidative stress-implicated gastrointestinal diseases. AB - Reactive oxygen species (ROS) attack guanine bases in DNA easily and form 8 hydroxydeoxyguanosine (8-OHdG), which can bind to thymidine rather than cytosine, based on which, the level of 8-OHdG is generally regarded as a biomarker of mutagenesis consequent to oxidative stress. For example, higher levels of 8-OHdG are noted in Helicobacter pylori-associated chronic atrophic gastritis as well as gastric cancer. However, we have found that exogenous 8-OHdG can paradoxically reduce ROS production, attenuate the nuclear factor-kappaB signaling pathway, and ameliorate the expression of proinflammatory mediators such as interleukin (IL) 1, IL-6, cyclo-oxygenase-2, and inducible nitric oxide synthase in addition to expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX)-1, NOX organizer-1 and NOX activator-1 in various conditions of inflammation-based gastrointestinal (GI) diseases including gastritis, inflammatory bowel disease, pancreatitis, and even colitis-associated carcinogenesis. Our recent finding that exogenous 8-OHdG was very effective in either inflammation-based or oxidative stress-associated diseases of stress-related mucosal damage has inspired the hope that synthetic 8-OHdG can be a potential candidate for the treatment of inflammation-based GI diseases, as well as the prevention of inflammation associated GI cancer. In this editorial review, the novel fact that exogenous 8 OHdG can be a functional molecule regulating oxidative-stress-induced gastritis through either antagonizing Rac-guanosine triphosphate binding or blocking the signals responsible for gastric inflammatory cascade is introduced. PMID- 22294837 TI - Embryonic hepatocyte transplantation for hepatic cirrhosis: efficacy and mechanism of action. AB - AIM: To investigate the efficacy and mechanism of action of allogeneic embryonic hepatocyte transplantation for the treatment of hepatic cirrhosis. METHODS: Rat embryonic hepatocytes were characterized by examining cell markers. Wistar rats with CCl(4)-induced cirrhosis were randomly divided into two groups: a model group receiving continuous CCl(4), and a cell transplantation group receiving continuous CCl(4) and transplanted with embryonic fluorescent-labeled hepatocytes. In addition, a normal control group was composed of healthy rats. All rats were sacrificed after 2 wk following the initiation of the cell transplant. Ultrasound, pathological analyses and serum biochemical tests were used to evaluate the efficacy of embryonic hepatocyte transplantation. To analyze the recovery status of cirrhotic hepatocytes and the signaling pathways influenced by embryonic hepatocyte transplantation, real-time polymerase chain reaction was performed to examine the mRNA expression of stellate activation associated protein (STAP), c-myb, alpha smooth muscle actin (alpha-SMA) and endothelin-1 (ET-1). Western blotting and immunohistochemistry were employed to detect alpha-SMA and ET-1 protein expression in hepatic tissues. RESULTS: Gross morphological, ultrasound and histopathological examinations, serum biochemical tests and radioimmunoassays demonstrated that hepatic cirrhosis was successfully established in the Wistar rats. Stem cell factor receptor (c-kit), hepatocyte growth factor receptor (c-Met), Nestin, alpha fetal protein, albumin and cytokeratin19 markers were observed in the rat embryonic hepatocytes. Following embryonic hepatocyte transplantation, there was a significant reversal in the gross appearance, ultrasound findings, histopathological properties, and serum biochemical parameters of the rat liver. In addition, after the activation of hepatic stellate cells and STAP signaling, alpha-SMA, c-myb and ET-1 mRNA levels became significantly lower than in the untreated cirrhotic group (P < 0.05). These levels, however, were not statistically different from those of the normal healthy group. Immunohistochemical staining and Western blot analyses revealed that alpha-SMA and ET-1 protein expression levels in the transplantation group were significantly lower than in the untreated cirrhotic group, but being not statistically different from the normal group. CONCLUSION: Transplantation of embryonic hepatocytes in rats has therapeutic effects on cirrhosis. The described treatment may significantly reduce the expression of STAP and ET-1. PMID- 22294838 TI - Liver cold preservation induce lung surfactant changes and acute lung injury in rat liver transplantation. AB - AIM: To investigate the relationship between donor liver cold preservation, lung surfactant (LS) changes and acute lung injury (ALI) after liver transplantation. METHODS: Liver transplantation models were established using male Wistar rats. Donor livers were preserved in University of Wisconsin solution at 4 degrees C for different lengths of time. The effect of ammonium pyrrolidinedithiocarbamate (PDTC) on ALI was also detected. All samples were harvested after 3 h reperfusion. The severity of ALI was evaluated by lung weight/body weight ratio, lung histopathological score, serum nitric oxide (NO) and endothelin (ET)-1 levels, lung tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta levels. Lung surfactants (LSs) were determined by micellar electrokinetic capillary chromatography. RESULTS: With extended donor liver cold preservation time (CPT), lung histopathological scores, serum ET-1 levels, lung weight/body weight ratio and the level of TNF-alpha and IL-1beta in lung were increased significantly in the 180-min group compared with the sham group (3.16 +/- 0.28 vs 1.12 +/- 0.21, P < 0.001; 343.59 +/- 53.97 vs 141.53 +/- 48.48, P < 0.001; 0.00687 +/- 0.00037 vs 0.00557 +/- 0.00056, P < 0.001; 17.5 +/- 3.0 vs 1.3 +/- 0.3, P < 0.001; 10.8 +/- 2.3 vs 1.8 +/- 0.4, P < 0.001), but serum NO levels decreased remarkably (74.67 +/- 10.01 vs 24.97 +/- 3.18, P < 0.001). The expression of lung phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylserine (PS) increased when CPT was < 120 min, and decreased when CPT was > 180 min (PC: 1318.89 +/- 54.79 vs 1011.18 +/- 59.99, P < 0.001; PE: 1504.45 +/- 119.96 vs 1340.80 +/- 76.39, P = 0.0019; PI: 201.23 +/- 34.82 vs 185.88 +/- 17.04, P = 0.2265; PS: 300.43 +/- 32.95 vs 286.55 +/- 55.55, P = 0.5054). All these ALI-associated indexes could be partially reversed by PDTC treatment. CONCLUSION: Prolonged CPT could induce or inhibit the expression of LSs at the compensation or decompensation stage, and some antioxidants (e.g., PDTC) may reverse the pathological process partially. PMID- 22294839 TI - Nitroglycerine effects on portal vein mechanics and oxidative stress in portal hypertension. AB - AIM: To examine the effects of nitroglycerine on portal vein haemodynamics and oxidative stress in patients with portal hypertension. METHODS: Thirty healthy controls and 39 patients with clinically verified portal hypertension and increased vascular resistance participated in the study. Liver diameters, portal diameters and portal flow velocities were recorded using color flow imaging/pulsed Doppler detection. Cross-section area, portal flow and index of vascular resistance were calculated. In collected blood samples, superoxide anion radical (O(2) (-)), hydrogen peroxide (H(2)O(2)), index of lipid peroxidation (measured as TBARS) and nitric oxide (NO) as a marker of endothelial response (measured as nitrite-NO(2) (-)) were determined. Time-dependent analysis was performed at basal state and in 10th and 15th min after nitroglycerine (sublingual 0.5 mg) administration. RESULTS: Oxidative stress parameters changed significantly during the study. H(2)O(2) decreased at the end of study, probably via O(2) (-) mediated disassembling in Haber Weiss and Fenton reaction; O(2) (-) increased significantly probably due to increased diameter and tension and decreased shear rate level. Consequently O(2) (-) and H(2)O(2) degradation products, like hydroxyl radical, initiated lipid peroxidation. Increased blood flow was to some extent lower in patients than in controls due to double paradoxes, flow velocity decreased, shear rate decreased significantly indicating non Newtonian characteristics of portal blood flow. CONCLUSION: This pilot study could be a starting point for further investigation and possible implementation of some antioxidants in the treatment of portal hypertension. PMID- 22294840 TI - alpha-fetoprotein, vascular endothelial growth factor receptor-1 and early recurrence of hepatoma. AB - AIM: To investigate whether alpha-fetoprotein (AFP) and vascular endothelial growth factor receptor (VEGFR)-1 correlate with early recurrence of hepatoma/hepatocellular carcinoma (HCC). METHODS: From 2000 to 2005, 114 consecutive patients with HCC underwent primary curative hepatectomy. The mean age was 60.7 (8.7) years and 94 patients were male. The median follow-up period was 71.2 mo (range: 43-100 mo). Immediately prior to commencing laparotomy, 5 mL bone marrow was aspirated from the sternum and collected in citrate-coated test tubes. The initial 2 mL of bone marrow aspirate was discarded in each case. AFP mRNA and VEGFR-1 mRNA in the bone marrow and peripheral blood (BM- and PH-AFP mRNA and BM- and PH-VEGFR-1 mRNA, respectively) were measured by real-time quantitative reverse transcription polymerase chain reaction. As normal controls, VEGFR-1 mRNA in the bone marrow and peripheral blood was also measured in 11 living liver donors. These data were evaluated for any correlation with early recurrence, comparing clinical and pathological outcomes. RESULTS: The cut-off value of the BM-AFP mRNA and PH-AFP mRNA level in patients with HCC was set at 1.92 * 10(-7) and zero, respectively, based on data from the controls. A total of 34 (29.8%) and six (5.4%) patients were positive for BM-AFP mRNA and PH-AFP mRNA, respectively. The BM-VEGFR-1 mRNA levels in all HCC patients were higher than those in the normal controls, and this was the case also for PH-VEGFR-1mRNA. The 25-percentile values for the BM- and PH-VEGFR-1 mRNA in HCC patients were used as the cut-off values for assigning the patients into two groups based on these transcript levels. The High group for BM- VEGFR-1 mRNA contained 81 (71.1%) HCC cases and the Low group was assigned 33 (28.9%) patients. These numbers for PH VEGFR-1mRNA were 78 (75.0%) and 26 (25.0%), respectively. HCC recurred in 80 patients; in the remnant liver in 48 cases, in the remnant liver and remote tissue in 20, and in the remote tissue alone in 12. BM-AFP mRNA-positive cases showed a significantly higher rate of early recurrence (within 1 year of surgical treatment) compared with BM-AFP mRNA-negative patients (P = 0.0091). Patients were classified into four groups according to the level/status of their BM-VEGFR 1 and BM-AFP mRNA as follows: group A (n = 23), BM-VEGFR-1/BM-AFP mRNA = low/negative; group B (n = 57) high/negative; group C (n = 10) low/positive; group D (n = 24), high/positive. This classification was found to correlate with a recurrence of this disease within 1 year (P = 0.0228). The disease-free survival curve of group A was significantly better than that of groups B, C or D (P = 0.0437, P = 0.0325, P = 0.0225). No other classification (i.e., PH-VEGF R1/BM-AFP, BM-VEGF-R1/PH-AFP, and PH-VEGF-R1/PH-AFP mRNA) showed such a correlation. CONCLUSION: The evaluation of BM-AFP and BM-VEGFR-1 mRNA in patients with HCC may be a valuable predictor of disease recurrence following curative resection. PMID- 22294841 TI - Adenovirus-expressed preS2 antibody inhibits hepatitis B virus infection and hepatic carcinogenesis. AB - AIM: To investigate the inhibitory effect of hepatitis B virus (HBV) preS2 antibody (preS2Ab) against HBV infection and HBV-associated hepatic carcinogenesis. METHODS: An adenoviral vector carrying the full-length light and heavy chains of the HBV preS2Ab gene, Ad315-preS2Ab, was constructed. Enzyme linked immunosorbent assay (ELISA) and Western blotting analyses were used to determine the preS2Ab expression levels in vitro. Immunofluorescent techniques were used to examine the binding affinity between the expressed HBV preS2Ab and HBV-positive liver cells. ELISAs were also used to determine hepatitis B surface antigen (HBsAg) levels to assess the inhibitory effect of the preS2Ab against HBV infection in L02 cells. The inhibitory effect of preS2Ab against hepatic carcinogenesis was studied with diethylnitrosamine (DEN)-induced hepatocellular carcinomas (HCCs) in HBV transgenic mice. RESULTS: The expression of HBV preS2Ab increased with increases in the multiplicity of infection (MOI) of Ad315-preS2Ab in L02 cells, with 350.87 +/- 17.37 MUg/L of preS2Ab when the MOI was 100 plaque forming units (pfu)/cell. The expressed preS2Abs could recognize liver cells from HBV transgenic mice. ELISA results showed that L02 cells expressing preS2Ab produced less HBsAg after treatment with the serum of HBV patients than parental L02 cells expressing no preS2Ab. HBV transgenic mice treated with Ad315-preS2Ab had fewer and smaller cancerous nodes after induction with DEN than mice treated with a blank Ad315 vector or untreated mice. Additionally, the administration of Ad315-preS2Ab could alleviate hepatic cirrhosis and decrease the serum levels of alanine transaminase and aspartate transaminase. CONCLUSION: Adenovirus-mediated HBV preS2Ab expression could inhibit HBV infection in L02 cells, and then inhibit DEN-induced hepatocellular carcinogenesis and protect hepatic function in HBV transgenic mice. PMID- 22294842 TI - Effects and mechanisms of store-operated calcium channel blockade on hepatic ischemia-reperfusion injury in rats. AB - AIM: To further investigate the important role of store-operated calcium channels (SOCs) in rat hepatocytes and to explore the effects of SOC blockers on hepatic ischemia-reperfusion injury (HIRI). METHODS: Using freshly isolated hepatocytes from a rat model of HIRI (and controls), we measured cytosolic free Ca(2+) concentration (by calcium imaging), net Ca(2+) fluxes (by a non-invasive micro test technique), the SOC current (I(SOC); by whole-cell patch-clamp recording), and taurocholate secretion [by high-performance liquid chromatography and 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays]. RESULTS: Ca(2+) oscillations and net Ca(2+) fluxes mediated by Ca(2+) entry via SOCs were observed in rat hepatocytes. I(SOC) was significantly higher in HIRI groups than in controls (57.0 +/- 7.5 pA vs 31.6 +/- 2.7 pA, P < 0.05) and was inhibited by La(3+). Taurocholate secretion by hepatocytes into culture supernatant was distinctly lower in HIRI hepatocytes than in controls, an effect reversed by SOC blockers. CONCLUSION: SOCs are pivotal in HIRI. SOC blockers protected against HIRI and assisted the recovery of secretory function in hepatocytes. Thus, they are likely to become a novel class of effective drugs for prevention or therapy of HIRI patients in the future. PMID- 22294843 TI - Polymorphisms of ICAM-1 are associated with gastric cancer risk and prognosis. AB - AIM: To investigate the association between single nucleotide polymorphisms (SNPs) in intercellular adhesion molecule-1 (ICAM-1) and the risk, biological behavior and prognosis of gastric cancer (GC) in Chinese population. METHODS: The study group consisted of 332 GC patients and 380 healthy controls. Genotyping was performed using polymerase chain reaction and the results were confirmed by sequencing. The association of ICAM-1 K469E polymorphisms and the risk of GC were studied, and the correlation of ICAM-1 K469E polymorphisms with the clinicopathological parameters and prognosis of the patients with complete clinical and follow-up data was analyzed. RESULTS: Carriers of AA genotype had a significantly increased risk of GC compared with carriers of AG and GG genotypes [odds ratios: 1.36; 95% confidence interval (CI): 1.01-1.84; P = 0.041]. GC patients with AA genotype were more prone to distant metastasis than those carrying AG and GG genotypes (18.9% vs 7.0%, respectively; P = 0.002). In addition, patients at stage IV had significantly more carriers of AA genotype than those of AG and GG genotype (27.4% vs 16.9%, respectively; P = 0.046). Follow-up study showed that the overall cumulative survival rate was 23.7% in AA genotype group and 42.9% in AG and GG genotypes group. In univariate analysis, AA genotype was correlated with the overall cumulative survival (P = 0.034). But in multivariate analysis, ICAM-1 polymorphism was not an independent prognostic factor for the overall survival (relative risk, 1.145; 95% CI: 0.851-1.540; P = 0.370). CONCLUSION: Polymorphisms of ICAM-1 K469E can be a useful biomarker for identifying individuals with higher risk of GC, predicting disease progression, and guiding individualized treatment. PMID- 22294844 TI - Population-based study of DNA image cytometry as screening method for esophageal cancer. AB - AIM: To explore the DNA image cytometry (DNA-ICM) technique as a primary screening method for esophageal squamous precancerous lesions. METHODS: This study was designed as a population-based screening study. A total of 582 local residents aged 40 years-69 years were recruited from Linzhou in Henan and Feicheng in Shandong. However, only 452 subjects had results of liquid-based cytology, DNA-ICM and pathology. The sensitivity and specificity of DNA-ICM were calculated and compared with liquid-based cytology in moderate dysplasia or worse. RESULTS: Sensitivities of DNA-ICM ranging from at least 1 to 4 aneuploid cells were 90.91%, 86.36%, 79.55% and 77.27%, respectively, which were better than that of liquid-based cytology (75%). Specificities of DNA-ICM were 70.83%, 84.07%, 92.65% and 96.81%, but the specificity of liquid-based cytology was 91.91%. The sensitivity and specificity of a combination of liquid-based cytology and DNA-ICM were 84.09% and 85.78%, respectively. CONCLUSION: It is possible to use DNA-ICM technique as a primary screening method for esophageal squamous precancerous lesions. PMID- 22294845 TI - A polymorphism within ErbB4 is associated with risk for hepatocellular carcinoma in Chinese population. AB - AIM: To investigate the association between hepatocellular carcinoma (HCC) susceptibility and a 12-bp insertion/deletion polymorphism (rs6147150) in the 3'UTR of ErbB4. METHODS: Using a case-control design, the rs6147150 genotypes in 270 patients with HCC and 270 healthy controls were determined by direct polymerase chain reaction and polyacrylamide gel electrophoresis. Logistic regression was used to analyze the association between the polymorphism and cancer risk. RESULTS: Computational modeling suggested that rs6147150 was located in the seed region of hsa-let-7c, a potential target sequence in ErbB4 3'UTR. Logistic regression analysis showed that, compared with individuals homozygous for wild-type, heterozygotes [adjusted odds ratio (OR) = 1.48, 95% confidence interval (CI) = 1.03-2.17, P = 0.034] and individuals homozygous for 12-bp del/del (OR = 2.50, 95% CI = 1.37-4.56, P = 0.001) were at significantly higher risk of HCC. Carriers of the "del" allele of rs6147150 had a 1.59-fold increased risk for HCC (95% CI = 1.22-2.07, P = 0.003). CONCLUSION: rs6147150 may be associated with HCC risk, in part through let-7c-mediated regulation, and may be involved in the pathogenesis of HCC in Chinese populations. PMID- 22294846 TI - No association between IRF3 polymorphism and susceptibility to hepatitis B virus infection in Chinese patients. AB - AIM: To investigate the association between three tag single nucleotide polymorphisms (tagSNPs) in interferon regulatory factors (IRF3) and the genetic susceptibility to chronic hepatitis B virus (HBV) infection. METHODS: We performed a case-control study of 985 Chinese cases of chronic HBV infection and 294 self-limiting HBV-infected individuals as controls. Three tagSNPs in IRF3 (rs10415576, rs2304204, rs2304206) were genotyped with the Multiplex SNaPshot technique. The genotype and allele frequencies were calculated and analyzed. RESULTS: The three SNPs showed no significant genotype/allele associations with chronic HBV infection. Overall allele P values were: rs10415576, P = 0.0908, odds ratio (OR) [95% confidence interval (CI)] = 1.1798 (0.9740-1.4291); rs2304204, P = 0.5959, OR (95% CI) = 1.0597 (0.8552-1.3133); rs2304206, P = 0.8372, OR (95% CI) = 1.0250 (0.8097-1.2976). Overall genotype P values were: rs10415576, P = 0.2106; rs2304204, P = 0.8458; rs2304206, P = 0.8315. There were no statistically significant differences between patients with chronic HBV infection and controls. Haplotypes generated by these three SNPs were also not significantly different between the two groups. CONCLUSION: The three tagSNPs of IRF3 are not associated with HBV infection in the Han Chinese population. PMID- 22294847 TI - Immediate effects from manual therapy: much ado about nothing? PMID- 22294848 TI - The relationship between hamstring length and gluteal muscle strength in individuals with sacroiliac joint dysfunction. AB - It has been suggested that tight hamstring muscle, due to its anatomical connections, could be a compensatory mechanism for providing sacroiliac (SI) joint stability in patients with gluteal muscle weakness and SIJ dysfunction. The purpose of this study was to determine the relationship between hamstring muscle length and gluteal muscle strength in subjects with sacroiliac joint dysfunction. A total of 159 subjects with and without low back pain (LBP) between the ages of 20 and 65 years participate in the study. Subjects were categorized into three groups: LBP without SIJ involvement (n = 53); back pain with SIJ dysfunction (n = 53); and no low back pain (n = 53). Hamstring muscle length and gluteal muscle strength were measured in all subjects. The number of individuals with gluteal weakness was significantly (P = 0.02) higher in subjects with SI joint dysfunction (66%) compared to those with LBP without SI joint dysfunctions (34%). In pooled data, there was no significant difference (P = 0.31) in hamstring muscle length between subjects with SI joint dysfunction and those with back pain without SI involvement. In subjects with SI joint dysfunction, however, those with gluteal muscle weakness had significantly (P = 0.02) shorter hamstring muscle length (mean = 158+/-11 degrees ) compared to individuals without gluteal weakness (mean = 165+/-10 degrees ). There was no statistically significant difference (P>0.05) in hamstring muscle length between individuals with and without gluteal muscle weakness in other groups. In conclusion, hamstring tightness in subjects with SI joint dysfunction could be related to gluteal muscle weakness. The slight difference in hamstring muscle length found in this study, although statistically significant, was not sufficient for making any definite conclusions. Further studies are needed to establish the role of hamstring muscle in SI joint stability. PMID- 22294849 TI - Placebo response to manual therapy: something out of nothing? AB - The mechanisms through which manual therapy inhibits musculoskeletal pain are likely multifaceted and related to the interaction between the intervention, the patient, the practitioner, and the environment. Placebo is traditionally considered an inert intervention; however, the pain research literature suggests that placebo is an active hypoalgesic agent. Placebo response likely plays a role in all interventions for pain and we suggest that the same is true for the treatment effects associated with manual therapy. The magnitude of a placebo response may be influenced by negative mood, expectation, and conditioning. We suggest that manual therapists conceptualize placebo not only as a comparative intervention, but also as a potential active mechanism to partially account for treatment effects associated with manual therapy. We are not suggesting manual therapists include known sham or ineffective interventions in their clinical practice, but take steps to maximize placebo responses to reduce pain. PMID- 22294850 TI - Patient expectations of benefit from common interventions for low back pain and effects on outcome: secondary analysis of a clinical trial of manual therapy interventions. AB - OBJECTIVES: The purpose of this secondary analysis was 1) to examine patient expectations related to a variety of common interventions for low back pain (LBP) and 2) to determine the influence that specific expectations about spinal manipulation might have had on self-report of disability. METHODS: We collected patients' expectations about the benefit of specific interventions for low back pain. We also collected patients' general expectations about treatment and tested the relationships among the expectation of benefit from an intervention, receiving that intervention and disability-related outcomes. RESULTS: Patients expected exercise and manual therapy interventions to provide more benefit than surgery and medication. There was a statistical association between expecting relief from thrust techniques and receiving thrust techniques, related to meeting the general expectation for treatment (chi-square: 15.5, P = 0.008). This was not the case for patients who expected relief from thrust techniques but did not receive it (chi-square: 6.9, P = 0.4). Logistic regression modeling was used to predict change in disability at treatment visit 5. When controlling for whether the general expectations for treatment were met, intervention assignment and the interaction between intervention assignment and expectations regarding thrust techniques, the parsimonious model only included intervention as the significant contributor to the model (P < 0.001). The adjusted odds ratio of success comparing thrust techniques to non-thrust in this study was 41.2 (11.0, 201.7). DISCUSSION: The findings of this secondary analysis indicate that patients seeking intervention for LBP expect active interventions and manual therapy to significantly help improve their pain more than interventions like traction, rest, surgery, or medication. Additionally, in patients who meet the clinical prediction rule for good prognosis when managed with thrust techniques, treating with thrust techniques is more important than matching treatment to patient expectation. PMID- 22294851 TI - The effects of neurodynamic mobilization on fluid dispersion within the tibial nerve at the ankle: an unembalmed cadaveric study. AB - OBJECTIVE: To evaluate the effects of neurodynamic mobilization on the fluid dynamics of the tibial nerve in cadavers. BACKGROUND: Evidence showing patients benefit from neural mobilization is limited. Mechanisms responsible for changes in patient symptoms are unclear. METHODS: Bilateral lower limbs of six unembalmed cadavers (n = 12) were randomized into matched pairs and dissected to expose the tibial nerve proximal to the ankle. Dye composed of Toulidine blue and plasma was injected into the nerve. The longitudinal dye spread was measured pre- and post mobilization. The experimental group received the intervention consisting of 30 repetitions of passive ankle range of motion over the course of 1 minute. The matched control limb received no mobilization. Data were analysed using a 2*2 repeated measures ANOVA with subsequent t-tests for pairwise comparisons. RESULTS: Mean dye spread was 23.8+/-10.2 mm, a change of 5.4+/-4.7% in the experimental limb as compared to 20.7+/-6.0 mm, a change of -1.5+/-3.9% in the control limb. The ANOVA was significant (P?0.02) for interaction between group (experimental/control) and time (pre-mobilization/post-mobilization). t-test results were significant between pre- and post-mobilization of the experimental leg (P = 0.01), and between control and experimental limbs post-mobilization (P?0.02). CONCLUSION: Passive neural mobilization induces dispersion of intraneural fluid. This may be clinically significant in the presence of intraneural edema found in pathological nerves such as those found in compression syndromes. PMID- 22294852 TI - Three-step treadmill test and McKenzie mechanical diagnosis and therapy to establish directional preference in a patient with lumbar spinal stenosis: a case report. AB - BACKGROUND: Lumbar spinal stenosis (LSS) is defined as narrowing of the spinal canal. LSS is commonly treated conservatively, primarily with flexion-based exercises. We present a patient diagnosed with LSS, refractory to a flexion-based protocol who ultimately responded to an extension-based protocol following establishment of directional preference with three-step treadmill testing. DESCRIPTION: A 64-year-old male was diagnosed with LSS with a 2-year history of bilateral neurogenic claudication unresponsive to flexion-based exercises. Initially, distinct directional preference or centralization was not demonstrated on repetitive movement testing. Ultimately, preference towards extension was established through a three-step treadmill test. An extension-based treatment plan was recommended, which provided significant relief despite focusing on exercises that are commonly avoided during traditional treatment for LSS. OUTCOMES: He began to centralize pain to his lower back after 2 weeks and denied neurogenic claudication on repeat three-step treadmill test at 3 weeks. His drastic improvements in pain levels and functional status continued throughout four sessions. DISCUSSION: Although the patient's initial diagnostic label may bias towards a spinal flexion protocol, further mechanical testing revealed an extension directional preference. The three-step treadmill test was crucial in establishing his directional preference and guiding his treatment. Treadmill testing may be useful in a subset of patients who do not demonstrate distinct directional preferences on mechanical testing. PMID- 22294853 TI - Classification-based approach for management of an adolescent with LBP, lower extremity pain, and a relevant postural deformity. AB - A 15-year-old female presented to physical therapy 2 months after a traumatic injury with severe low back pain, referred unilateral leg pain below the knee, and a lumbar lateral shift. A classification-based approach, mechanical diagnosis and therapy, was utilized to identify the patient with respect to a particular subgroup, and interventions were applied according to symptomatic response to loading strategies, sustained and repeated movements. Outcome measures included the Modified Oswestry Disability Questionnaire (MODQ) and a visual analog scale (VAS) for pain rating. After nine visits (4 weeks), there was a 60% improvement in MODQ score, 0/10 pain on the VAS, and the patient resumed participation in recreational activities. At the 1-year follow-up, there was a 78% overall improvement in MODQ score with continued 0/10 rated pain. Improvements after nine visits and at the 1-year follow-up both exceeded the minimal clinically important difference for the MODQ. PMID- 22294854 TI - High frequency of McKenzie's postural syndrome in young population of non-care seeking individuals. AB - OBJECTIVES: The role of postural loads as a risk factor for back pain and musculoskeletal symptoms is unclear. McKenzie proposed in his classification of mechanical syndromes a postural syndrome, in which people only develop symptoms from sustained loading, which is relieved by a change in position and has no effect on movement or function. Because of the low level disability with postural syndrome, it was suggested that few seek healthcare for this problem. METHODS: This study used a two-stage process first to give a questionnaire to 100 students and staff from a university to determine who appeared to have postural syndrome, and then applied a physical examination to those who consented. RESULTS: One hundred and thirty-eight were approached, of who 100 completed questionnaires and 66% appeared to have postural syndrome. Of the 66 who appeared to have postural syndrome, 37 consented to have a physical examination. Of the 37, 31 met the criteria for postural syndrome, with postural syndrome being significantly associated with pain on sustained loading and pain abolition on posture correction. Most postural syndrome was in the lumbar spine and associated with sitting, but other sites and causes were also noted. DISCUSSION: This study lends credibility to McKenzie's postural syndrome, but also suggests this as a possible precursor for future more disabling or painful problems. Postural syndrome may not feature in those seeking professional healthcare, but is clearly highly prevalent in a young population. PMID- 22294855 TI - Clinical equipoise and personal equipoise: two necessary ingredients for reducing bias in manual therapy trials. AB - Clinical and personal equipoise exists when a clinician has no good basis for a choice between two or more care options or when one is truly uncertain about the overall benefit or harm offered by the treatment to his/her patient. For most manual therapy trials, equipoise does not likely exist. Because of the nature of the intervention a lack of equipoise can lead to bias and may account for a portion of the 'effect' that has traditionally been assigned to the intervention. Although there are methodological mechanisms to reduce the risk of bias associated with a lack of equipoise, most of the manual therapy trials to date are likely guilty of this form of bias. PMID- 22294856 TI - Synthesis, Crystal Structure, and Rotational Energy Profile of 3-Cyclopropyl 1,2,4-benzotriazine 1,4-Di-N-oxide. AB - 1,2,4-Benzotriazine 1,4-di-N-oxides are potent antitumor drug candidates that undergo in vivo bioreduction leading to selective DNA damage in the low oxygen (hypoxic) cells found in tumors. Tirapazamine (TPZ) is the lead compound in this family. Here we report on the synthesis, crystal structure, and conformational analysis of a new analog, 3-cyclopropyl-1,2,4-benzotriazine 1,4-di-N-oxide (3). Compound 3 (C(10)H(10)N(3)O(2)) crystallized in the monoclinic space group C2/c. Unit cell parameters for 3: a = 16.6306 (12), b = 7.799 (5), c = 16.0113 (11) A, alpha = 90, beta = 119.0440 (10), gamma = 90, and z = 8. PMID- 22294857 TI - Recent developments in the epidemiology and management of tuberculosis - new solutions to old problems? AB - Tuberculosis is an ancient human disease that is still a major cause of death and one of the most challenging public health problems worldwide. After decades of stagnancy, new public-private partnerships to fight the disease and the increasing awareness of a vicious circle between the tuberculosis epidemic and the obstruction of economic development have fuelled recent progress in our understanding of the disease. As a result, new strategies to improve management and treatment of tuberculosis have been initiated. At the same time, however, the devastating effect of human immunodeficiency virus on tuberculosis susceptibility and the rapid expansion of multidrug-resistant (MDR) tuberculosis threaten to undermine the advances made by tuberculosis management programs. With an estimated 9 million new cases annually, tuberculosis affects a higher number of individuals worldwide than ever before. Here, recent developments in the epidemiology and management of tuberculosis are summarized and an overview is provided of emerging strategies to combat this ancient scourge. PMID- 22294858 TI - Safety and efficacy of liposomal amphotericin B for the empirical therapy of invasive fungal infections in immunocompromised patients. AB - Liposomal amphotericin B is a "true" liposomal formulation of amphotericin B with greatly reduced nephrotoxicity and minimal infusion-related toxicity. This broad spectrum polyene is well tolerated and effective against most invasive fungal infections. In view of the current limitations on diagnostic capability of invasive fungal infections, most clinicians are often compelled to use antifungal drugs in an empiric manner; liposomal amphotericin B continues to play an important role in the empiric management of invasive fungal infections, despite the recent availability of several other drugs in the azole and echinocandin classes. PMID- 22294859 TI - Evaluation of the use of piperacillin/tazobactam (Tazocin) at Hamad General Hospital, Qatar: are there unjustified prescriptions? AB - OBJECTIVES: The aim of this study was to evaluate the appropriateness of piperacillin/tazobactam (Tazocin((r)); Pfizer, New York, NY) usage in our hospital. SUBJECTS AND METHODS: This retrospective study was designed to involve all patients admitted to Hamad General Hospital and prescribed piperacillin/tazobactam as an empiric therapy from January 1 to March 31, 2008. The medical records of such patients were retrospectively reviewed and studied. RESULTS: During this period, 610 prescriptions were ordered for 596 patients. The main indication for initiation of Tazocin was sepsis (207/610; 34%). The overall rate of appropriateness of empirical therapy was 348/610 (57%). Most of the inappropriate prescriptions were in cases of aspiration pneumonia and abdominal infections, with inappropriate prescriptions found mostly in surgical wards (86%) and the surgical intensive care unit (66.7%). Septic work-up results showed positive cultures in 57% (345/610) of cases. There were 198/254 prescriptions (78%) where antibiotics were changed according to the sensitivity data to narrow spectrum antimicrobials. In 56/254 (22%) cases, pathogens were susceptible to narrow-spectrum antibiotics even though piperacillin/tazobactam was continued. CONCLUSION: Our study showed that there was an injudicious use of piperacillin/tazobactam at our hospital, evidenced by the significant number of inappropriate empiric prescriptions and inappropriate drug modifications, based on the results of microbial cultures and antibiograms. PMID- 22294860 TI - Ceftaroline in complicated skin and skin-structure infections. AB - Ceftaroline is an advanced-generation cephalosporin antibiotic recently approved by the US Food and Drug Administration for the treatment of complicated skin and skin-structure infections (cSSSIs). This intravenous broad-spectrum antibiotic exerts potent bactericidal activity by inhibiting bacterial cell wall synthesis. A high affinity for the penicillin-binding protein 2a (PBP2a) of methicillin resistant Staphylococcus aureus (MRSA) makes the drug especially beneficial to patients with MRSA cSSSIs. Ceftaroline has proved in multiple well-conducted clinical trials to have an excellent safety and efficacy profile. In adjusted doses it is also recommended for patients with renal or hepatic impairment. Furthermore, the clinical effectiveness and high cure rate demonstrated by ceftaroline in cSSSIs, including those caused by MRSA and other multidrug resistant strains, warrants its consideration as a first-line treatment option for cSSSIs. This article reviews ceftaroline and its pharmacology, efficacy, and safety data to further elucidate its role in the treatment of cSSSIs. PMID- 22294862 TI - Pearls. PMID- 22294861 TI - Conjunctival sac bacterial flora isolated prior to cataract surgery. AB - OBJECTIVE: To determine the trends of conjunctival sac bacterial flora isolated from patients prior to cataract surgery. SUBJECTS AND METHODS: The study comprised 579 patients (579 eyes) who underwent cataract surgery. Specimens were collected by lightly rubbing the inferior palpebral conjunctival sac with a sterile cotton swab 2 weeks before surgery, and then cultured for isolation of bacteria and antimicrobial sensitivity testing. The bacterial isolates and percentage of drug-resistant isolates were compared among age groups and according to whether or not patients had diabetes mellitus, hyperlipidemia, dialysis therapy, oral steroid use, dry eye syndrome, or allergic conjunctivitis. RESULTS: The bacterial isolation rate was 39.2%. There were 191 strains of Gram positive cocci, accounting for the majority of all isolates (67.0%), among which methicillin-sensitive coagulase-negative staphylococci was the most frequent (127 strains, 44.5%), followed by methicillin-resistant coagulase-negative staphylococci (37 strains, 12.7%). All 76 Gram-positive bacillary isolates (26.7%) were from the genus Corynebacterium. Among the 16 Gram-negative bacillary isolates (5.9%), the most frequent was Escherichia coli (1.0%). The bacterial isolation rate was higher in patients >60 years old, and was lower in patients with dry eye syndrome, patients under topical treatment for other ocular disorders, and patients with hyperlipidemia. There was no significant difference in bacterial isolation rate with respect to the presence/absence of diabetes mellitus, steroid therapy, dialysis, or a history of allergic conjunctivitis. Methicillin-resistant coagulase-negative staphylococci showed a significantly higher detection rate in diabetic patients than nondiabetic patients (20.3% versus 7.0%, P < 0.05). The percentage of all isolates resistant to levofloxacin, cefmenoxime, and tobramycin was 14.0%, 15.2%, and 17.9%, respectively, with no significant differences among these drugs. CONCLUSION: The high bacterial isolation rate in patients >60 years old and the high methicillin-resistant coagulase-negative staphylococci isolation rate in patients with diabetes are important to consider for prevention of perioperative infections. PMID- 22294863 TI - Case 1: Fever and a genital ulcer in a recent immigrant. PMID- 22294864 TI - Case 2: The perspiring infant. PMID- 22294865 TI - The art of listening: Bony lesion in a toddler. PMID- 22294866 TI - Long-distance air transport of an infant weighing less than 500 g: Is it in the patient's best interest? AB - When a preterm infant is delivered in a region where resources are limited, long distance air transport may be required. However, such transport is a significant stressor on an extremely fragile patient, and the neonate's best interest must be evaluated. The current article presents the case of the smallest infant ever reported to have been transported by air, over more than 2300 km, and reflects on clinical and ethical challenges. Is a fragile 450 g baby born in a developing country better off spending the first week of his/her life where he/she was born, or risking a difficult transport to where he/she could have optimal care? What if this baby had already suffered a significant intraventricular hemorrhage? What if we were transporting the baby to provide palliative care 'at home'? These questions are discussed to illustrate the complexity of the decision-making process, and to facilitate a debate on transport of such fragile patients. PMID- 22294867 TI - Vitamin D concentrations among healthy children in Calgary, Alberta. AB - OBJECTIVE: To examine the relationship between serum vitamin D concentrations, dietary intake and body mass index among healthy children living in Calgary, Alberta. METHODS: The present cross-sectional study included healthy children two to 13 years of age who presented to the Alberta Children's Hospital for elective surgery during a 12-month period. Data including the child's weight, height, age, sex, ethnicity, dietary intake, use of vitamin supplements, physical activity and time spent outdoors were collected. Serum concentrations of 25-hydroxyvitamin D (25[OH]D) were measured using commercial immunoradiometric assay kits. RESULTS: Serum 25(OH)D concentrations were available for 1442 of 1862 participants, of whom 862 (59.8%) were boys. The mean (+/- SD) serum 25(OH)D concentration was 86.1+/-35.1 nmol/L (range 10 nmol/L to 323 nmol/L). Five hundred thirty-nine (37.4%) participants had insufficient vitamin D status (25[OH]D between 25 nmol/L and lower than 75 nmol/L), and vitamin D deficiency (25[OH]D 25 nmol/L or lower) was present in 29 subjects (2.0%). Children in the older age group (nine to 13 years) were more likely to have suboptimal vitamin D (P<0.001). Other risk factors significantly associated with suboptimal vitamin D status included overweight or obesity, nonwhite ethnicity, winter months, dietary vitamin D intake of less than 200 IU/day and less time spent outdoors. CONCLUSION: A high rate of suboptimal vitamin D concentrations was observed among the participants. Beyond promoting a vitamin D-enriched diet, physicians should also consider the body mass index and other risk factors to determine the optimal vitamin D intake for children living in the area studied. PMID- 22294868 TI - Chest compressions and epinephrine during resuscitation of infants born at the border of viability: Yes, no or maybe? AB - Neonatology, in large part due to its population of babies born at the edge of viability, is rife with bioethical issues. This unique population is at high risk of mortality and considerable neurodevelopmental morbidity. One contentious, ongoing debate concerns whether these extremely low birth weight infants born at the border of viability should, if required by the Neonatal Resuscitation Program guidelines, receive chest compressions and epinephrine as part of their delivery room resuscitation. The present article, through a case presentation and discussion based on the ethical framework of principlism, provides readers with a thoughtful approach to the controversial issue of the provision of chest compressions and epinephrine as part of resuscitation for extremely low birth weight infants born at the border of viability. PMID- 22294869 TI - Emergency management of the paediatric patient with generalized convulsive status epilepticus. AB - The present guideline paper addresses the emergency management of generalized convulsive status epilepticus (CSE) in children and infants older than one month of age. It replaces the previous statement from 1996, and includes a new treatment algorithm and table of recommended medications, reflecting new evidence and the evolution of clinical practice over the past 15 years. The document focuses on the acute pharmacological management of CSE, but some issues regarding supportive care, diagnostic approach and treatment of refractory CSE are discussed. PMID- 22294870 TI - Home intravenous therapy: Accessibility for Canadian children and youth. AB - The administration of intravenous (IV) therapy at home is an alternative to hospitalization for treatment of infection and a number of other conditions, and has been demonstrated to be effective and safe, to reduce cost and to improve quality of life. While home IV therapy has many advantages for children, it is not uniformly available and access may be limited by age, geographical location and ability to pay. Physicians caring for children need to be aware of the indications for home IV therapy, its requirements and limitations, as well as whether this option is available for children in their care. Where access is limited, physicians should advocate for home IV therapy for children when it is medically indicated. PMID- 22294871 TI - Management of community-associated methicillin-resistant Staphylococcus aureus skin abscesses in children. AB - Uncomplicated skin abscesses in previously well children are typically managed with drainage alone. An increasing percentage of such abscesses are due to methicillin-resistant Staphylococcus aureus infections. Although definitive data are lacking, drainage alone appears to be a reasonable strategy for methicillin resistant S aureus skin abscesses, with antibiotics reserved for infants younger than three months of age, or for children who are systemically unwell, have underlying medical problems or have significant surrounding cellulitis. PMID- 22294872 TI - Prevalence and predictors of low vitamin D concentrations in urban Canadian toddlers. AB - OBJECTIVES: To determine the prevalence of low vitamin D concentrations in a cohort of healthy two-year-old children living in a large Canadian city, and to explore whether body mass index (BMI) and cow's milk intake are associated with low vitamin D concentrations. METHODS: A cross-sectional study was performed on healthy two-year-old children attending a well-child visit in Toronto, Ontario (latitude 43.4 degrees N). Dietary exposures were measured by questionnaire. The primary outcome was the prevalence of low vitamin D concentrations (25 hydroxyvitamin D concentration of lower than 50 nmol/L or lower than 75 nmol/L). RESULTS: A total of 91 healthy children 24 to 30 months of age were recruited between November 2007 and May 2008. The prevalence of low vitamin D concentrations (lower than 50 nmol/L) was 32% (29 of 92, 95% CI 22% to 42%) and the prevalence of vitamin D concentrations of lower than 75 nmol/L was 82% (75 of 91, 95% CI 73% to 89%). Using multivariable logistic regression, the odds of vitamin D concentrations being lower than 50 nmol/L decreased by 0.44 (95% CI 0.2 to 0.96) for each additional cup of cow's milk intake per day and increased by 1.2 to 2.6 per unit BMI depending on BMI level (P=0.07). CONCLUSIONS: A total of 30% to 80% of toddlers in the present study's urban Canadian setting demonstrated low vitamin D concentrations - the highest prevalence of low vitamin D in toddlers outside of Alaska. Modifiable factors associated with low vitamin D were lower cow's milk intake and higher BMI. The vitamin D status of toddlers in urban Canada may require specific attention. PMID- 22294873 TI - Abusive head trauma in infants and why we CAN afford to prevent it. PMID- 22294874 TI - Cell death pathways as therapeutic targets in rhabdomyosarcoma. AB - Resistance of rhabdomyosarcoma to current therapies remains one of the key issues in pediatric oncology. Since the success of most cytotoxic therapies in the treatment of cancer, for example, chemotherapy, depends on intact signaling pathways that mediate programmed cell death (apoptosis), defects in apoptosis programs in cancer cells may result in resistance. Evasion of apoptosis in rhabdomyosarcoma may be caused by defects in the expression or function of critical mediators of apoptosis or in aberrant expression of antiapoptotic proteins. Therefore, the identification of the molecular mechanisms that confer primary or acquired resistance to apoptosis in rhabdomyosarcoma presents a critical step for the rational development of molecular targeted drugs. This approach will likely open novel perspectives for the treatment of rhabdomyosarcoma. PMID- 22294875 TI - Genetics and mitochondrial abnormalities in autism spectrum disorders: a review. AB - We review the current status of the role and function of the mitochondrial DNA (mtDNA) in the etiology of autism spectrum disorders (ASD) and the interaction of nuclear and mitochondrial genes. High lactate levels reported in about one in five children with ASD may indicate involvement of the mitochondria in energy metabolism and brain development. Mitochondrial disturbances include depletion, decreased quantity or mutations of mtDNA producing defects in biochemical reactions within the mitochondria. A subset of individuals with ASD manifests copy number variation or small DNA deletions/duplications, but fewer than 20 percent are diagnosed with a single gene condition such as fragile X syndrome. The remaining individuals with ASD have chromosomal abnormalities (e.g., 15q11 q13 duplications), other genetic or multigenic causes or epigenetic defects. Next generation DNA sequencing techniques will enable better characterization of genetic and molecular anomalies in ASD, including defects in the mitochondrial genome particularly in younger children. PMID- 22294876 TI - The illusion of distribution-free small-sample classification in genomics. AB - Classification has emerged as a major area of investigation in bioinformatics owing to the desire to discriminate phenotypes, in particular, disease conditions, using high-throughput genomic data. While many classification rules have been posed, there is a paucity of error estimation rules and an even greater paucity of theory concerning error estimation accuracy. This is problematic because the worth of a classifier depends mainly on its error rate. It is common place in bio-informatics papers to have a classification rule applied to a small labeled data set and the error of the resulting classifier be estimated on the same data set, most often via cross-validation, without any assumptions being made on the underlying feature-label distribution. Concomitant with a lack of distributional assumptions is the absence of any statement regarding the accuracy of the error estimate. Without such a measure of accuracy, the most common one being the root-mean-square (RMS), the error estimate is essentially meaningless and the worth of the entire paper is questionable. The concomitance of an absence of distributional assumptions and of a measure of error estimation accuracy is assured in small-sample settings because even when distribution-free bounds exist (and that is rare), the sample sizes required under the bounds are so large as to make them useless for small samples. Thus, distributional bounds are necessary and the distributional assumptions need to be stated. Owing to the epistemological dependence of classifiers on the accuracy of their estimated errors, scientifically meaningful distribution-free classification in high throughput, small-sample biology is an illusion. PMID- 22294877 TI - The MADS and the Beauty: Genes Involved in the Development of Orchid Flowers. AB - Since the time of Darwin, biologists have studied the origin and evolution of the Orchidaceae, one of the largest families of flowering plants. In the last two decades, the extreme diversity and specialization of floral morphology and the uncoupled rate of morphological and molecular evolution that have been observed in some orchid species have spurred interest in the study of the genes involved in flower development in this plant family. As part of the complex network of regulatory genes driving the formation of flower organs, the MADS-box represents the most studied gene family, both from functional and evolutionary perspectives. Despite the absence of a published genome for orchids, comparative genetic analyses are clarifying the functional role and the evolutionary pattern of the MADS-box genes in orchids. Various evolutionary forces act on the MADS-box genes in orchids, such as diffuse purifying selection and the relaxation of selective constraints, which sometimes reveals a heterogeneous selective pattern of the coding and non-coding regions. The emerging theory regarding the evolution of floral diversity in orchids proposes that the diversification of the orchid perianth was a consequence of duplication events and changes in the regulatory regions of the MADS-box genes, followed by sub- and neo-functionalization. This specific developmental-genetic code is termed the "orchid code." PMID- 22294878 TI - Stemming epigenetics in marine stramenopiles. AB - Epigenetics include DNA methylation, the modification of histone tails that affect chromatin states, and small RNAs that are involved in the setting and maintenance of chromatin modifications. Marine stramenopiles (MAS), which are a diverse assemblage of algae that acquired photosynthesis from secondary endosymbiosis, include single-celled organisms such as diatoms as well as multicellular forms such as brown algae. The recent publication of two diatom genomes that diverged ~90 million years ago (mya), as well as the one of a brown algae that diverged from diatoms ~250 Mya, provide a great system of related, yet diverged set of organisms to compare epigenetic marks and their relationships. For example, putative DNA methyltransferase homologues were found in diatoms while none could be identified in the brown algal genome. On the other hand, no canonical DICER-like protein was found in diatoms in contrast to what is observed in brown algae. A key interest relies in understanding the adaptive nature of epigenetics and its inheritability. In contrast to yeast that lack DNA methylation, homogeneous cultures of diatoms constitute an attractive system to study epigenetic changes in response to environmental conditions such as nutrient rich to nutrient-poor transitions which is especially relevant because of their ecological importance. P. tricornutum is also of outstanding interest because it is observed as three different morphotypes and thus constitutes a simple and promising model for the study of the epigenetic phenomena that accompany cellular differentiation. In this review we focus on the insights obtained from MAS comparative genomics and epigenomic analyses. PMID- 22294879 TI - The genetics of vitamin C loss in vertebrates. AB - Vitamin C (ascorbic acid) plays important roles as an anti-oxidant and in collagen synthesis. These important roles, and the relatively large amounts of vitamin C required daily, likely explain why most vertebrate species are able to synthesize this compound. Surprisingly, many species, such as teleost fishes, anthropoid primates, guinea pigs, as well as some bat and Passeriformes bird species, have lost the capacity to synthesize it. Here, we review the genetic bases behind the repeated losses in the ability to synthesize vitamin C as well as their implications. In all cases so far studied, the inability to synthesize vitamin C is due to mutations in the L-gulono-gamma-lactone oxidase (GLO) gene which codes for the enzyme responsible for catalyzing the last step of vitamin C biosynthesis. The bias for mutations in this particular gene is likely due to the fact that losing it only affects vitamin C production. Whereas the GLO gene mutations in fish, anthropoid primates and guinea pigs are irreversible, some of the GLO pseudogenes found in bat species have been shown to be reactivated during evolution. The same phenomenon is thought to have occurred in some Passeriformes bird species. Interestingly, these GLO gene losses and reactivations are unrelated to the diet of the species involved. This suggests that losing the ability to make vitamin C is a neutral trait. PMID- 22294880 TI - Automatically augmenting lifelog events using pervasively generated content from millions of people. AB - In sensor research we take advantage of additional contextual sensor information to disambiguate potentially erroneous sensor readings or to make better informed decisions on a single sensor's output. This use of additional information reinforces, validates, semantically enriches, and augments sensed data. Lifelog data is challenging to augment, as it tracks one's life with many images including the places they go, making it non-trivial to find associated sources of information. We investigate realising the goal of pervasive user-generated content based on sensors, by augmenting passive visual lifelogs with "Web 2.0" content collected by millions of other individuals. PMID- 22294881 TI - Achieving network level privacy in Wireless Sensor Networks. AB - Full network level privacy has often been categorized into four sub-categories: Identity, Route, Location and Data privacy. Achieving full network level privacy is a critical and challenging problem due to the constraints imposed by the sensor nodes (e.g., energy, memory and computation power), sensor networks (e.g., mobility and topology) and QoS issues (e.g., packet reach-ability and timeliness). In this paper, we proposed two new identity, route and location privacy algorithms and data privacy mechanism that addresses this problem. The proposed solutions provide additional trustworthiness and reliability at modest cost of memory and energy. Also, we proved that our proposed solutions provide protection against various privacy disclosure attacks, such as eavesdropping and hop-by-hop trace back attacks. PMID- 22294882 TI - Paper actuators made with cellulose and hybrid materials. AB - Recently, cellulose has been re-discovered as a smart material that can be used as sensor and actuator materials, which is termed electro-active paper (EAPap). This paper reports recent advances in paper actuators made with cellulose and hybrid materials such as multi-walled carbon nanotubes, conducting polymers and ionic liquids. Two distinct actuator principles in EAPap actuators are demonstrated: piezoelectric effect and ion migration effect in cellulose. Piezoelectricity of cellulose EAPap is quite comparable with other piezoelectric polymers. But, it is biodegradable, biocompatible, mechanically strong and thermally stable. To enhance ion migration effect in the cellulose, polypyrrole conducting polymer and ionic liquids were nanocoated on the cellulose film. This hybrid cellulose EAPap nanocomposite exhibits durable bending actuation in an ambient humidity and temperature condition. Fabrication, characteristics and performance of the cellulose EAPap and its hybrid EAPap materials are illustrated. Also, its possibility for remotely microwave-driven paper actuator is demonstrated. PMID- 22294883 TI - Reliable asynchronous image transfer protocol in wireless multimedia sensor networks. AB - In the paper, we propose a reliable asynchronous image transfer protocol, RAIT. RAIT applies a double sliding window method to node-to-node transfer, with one sliding window for the receiving queue, which is used to prevent packet loss caused by communication failure between nodes, and another sliding window for the sending queue, which prevents packet loss caused by network congestion. The routing node prevents packet loss between nodes by preemptive scheduling of multiple packets for a given image. RAIT implements a double sliding window method by means of a cross-layer design between the RAIT layer, routing layer, and queue layer. We demonstrate that RAIT guarantees a higher reliability of image transmission compared to the existing protocols. PMID- 22294884 TI - Concurrent initialization for Bearing-Only SLAM. AB - Simultaneous Localization and Mapping (SLAM) is perhaps the most fundamental problem to solve in robotics in order to build truly autonomous mobile robots. The sensors have a large impact on the algorithm used for SLAM. Early SLAM approaches focused on the use of range sensors as sonar rings or lasers. However, cameras have become more and more used, because they yield a lot of information and are well adapted for embedded systems: they are light, cheap and power saving. Unlike range sensors which provide range and angular information, a camera is a projective sensor which measures the bearing of images features. Therefore depth information (range) cannot be obtained in a single step. This fact has propitiated the emergence of a new family of SLAM algorithms: the Bearing-Only SLAM methods, which mainly rely in especial techniques for features system-initialization in order to enable the use of bearing sensors (as cameras) in SLAM systems. In this work a novel and robust method, called Concurrent Initialization, is presented which is inspired by having the complementary advantages of the Undelayed and Delayed methods that represent the most common approaches for addressing the problem. The key is to use concurrently two kinds of feature representations for both undelayed and delayed stages of the estimation. The simulations results show that the proposed method surpasses the performance of previous schemes. PMID- 22294885 TI - A new electronic monitoring device to measure medication adherence: usability of the Helping HandTM. AB - The aim of this study was to test the user performance, satisfaction and acceptability of the Helping HandTM (B&O Medicom) electronic medication adherence monitor. Using a mixed-method design, we studied 11 kidney transplant patients and 10 healthy volunteers during three weeks. Although testing showed positive usability aspects, several areas requiring technical improvement were identified: the most important obstacles to usability and acceptability were the weak sound signal, problems loading the medication, and the fact that only one medication could be used at a time. PMID- 22294886 TI - Geometric stability and lens decentering in compact digital cameras. AB - A study on the geometric stability and decentering present in sensor-lens systems of six identical compact digital cameras has been conducted. With regard to geometrical stability, the variation of internal geometry parameters (principal distance, principal point position and distortion parameters) was considered. With regard to lens decentering, the amount of radial and tangential displacement resulting from decentering distortion was related with the precision of the camera and with the offset of the principal point from the geometric center of the sensor. The study was conducted with data obtained after 372 calibration processes (62 per camera). The tests were performed for each camera in three situations: during continuous use of the cameras, after camera power off/on and after the full extension and retraction of the zoom-lens. Additionally, 360 new calibrations were performed in order to study the variation of the internal geometry when the camera is rotated. The aim of this study was to relate the level of stability and decentering in a camera with the precision and quality that can be obtained. An additional goal was to provide practical recommendations about photogrammetric use of such cameras. PMID- 22294887 TI - A z-axis quartz cross-fork micromachined gyroscope based on shear stress detection. AB - Here we propose a novel quartz micromachined gyroscope. The sensor has a simple cross-fork structure in the x-y plane of quartz crystal. Shear stress rather than normal stress is utilized to sense Coriolis' force generated by the input angular rate signal. Compared to traditional quartz gyroscopes, which have two separate sense electrodes on each sidewall, there is only one electrode on each sidewall of the sense beam. As a result, the fabrication of the electrodes is simplified and the structure can be easily miniaturized. In order to increase sensitivity, a pair of proof masses is attached to the ends of the drive beam, and the sense beam has a tapered design. The structure is etched from a z-cut quartz wafer and the electrodes are realized by direct evaporation using the aperture mask method. The drive mode frequency of the prototype is 13.38 kHz, and the quality factor is approximately 1,000 in air. Therefore, the gyroscope can work properly without a vacuum package. The measurement ability of the shear stress detection design scheme is validated by the Coriolis' force test. The performance of the sensor is characterized on a precision rate table using a specially designed readout circuit. The experimentally obtained scale factor is 1.45 mV/ degrees /s and the nonlinearity is 3.6% in range of +/- 200 degrees /s. PMID- 22294888 TI - Conductometric soot sensor for automotive exhausts: initial studies. AB - In order to reduce the tailpipe particulate matter emissions of Diesel engines, Diesel particulate filters (DPFs) are commonly used. Initial studies using a conductometric soot sensor to monitor their filtering efficiency, i.e., to detect a malfunction of the DPF, are presented. The sensors consist of a planar substrate equipped with electrodes on one side and with a heater on the other. It is shown that at constant speed-load points, the time until soot percolation occurs or the resistance itself are reproducible means that can be well correlated with the filtering efficiency of a DPF. It is suggested to use such a sensor setup for the detection of a DPF malfunction. PMID- 22294889 TI - Mobile sensor networks for inspection tasks in harsh industrial environments. AB - Recent advances in sensor technology have enabled the fast development of mobile sensor networks operating in various unknown and sometimes hazardous environments. In this paper, we introduce one integrative approach to design, analyze and test distributed control algorithms to coordinate a network of autonomous mobile sensors by utilizing both simulation tools and a robotic testbed. The research has been carried out in the context of the mobile sensing project, PicoSmart, in the northern provinces of the Netherlands for the inspection of natural gas pipelines. PMID- 22294890 TI - An enhanced backbone-assisted reliable framework for wireless sensor networks. AB - An extremely reliable source to sink communication is required for most of the contemporary WSN applications especially pertaining to military, healthcare and disaster-recovery. However, due to their intrinsic energy, bandwidth and computational constraints, Wireless Sensor Networks (WSNs) encounter several challenges in reliable source to sink communication. In this paper, we present a novel reliable topology that uses reliable hotlines between sensor gateways to boost the reliability of end-to-end transmissions. This reliable and efficient routing alternative reduces the number of average hops from source to the sink. We prove, with the help of analytical evaluation, that communication using hotlines is considerably more reliable than traditional WSN routing. We use reliability theory to analyze the cost and benefit of adding gateway nodes to a backbone-assisted WSN. However, in hotline assisted routing some scenarios where source and the sink are just a couple of hops away might bring more latency, therefore, we present a Signature Based Routing (SBR) scheme. SBR enables the gateways to make intelligent routing decisions, based upon the derived signature, hence providing lesser end-to-end delay between source to the sink communication. Finally, we evaluate our proposed hotline based topology with the help of a simulation tool and show that the proposed topology provides manifold increase in end-to-end reliability. PMID- 22294891 TI - How accurate are electronic monitoring devices? A laboratory study testing two devices to measure medication adherence. AB - In a prospective descriptive laboratory study, 25 Helping Hand(TM) (HH) (10 without and 15 with reminder system) and 50 Medication Event Monitoring Systems (MEMS) (25 with 18-month and 25 with 2-year battery life) were manipulated twice daily following a predefined protocol during 3 consecutive weeks. Accuracy was determined using the fixed manipulation scheme as the reference. Perfect functioning (i.e., total absence of missing registrations and/or overregistrations) was observed in 70% of the HH without, 87% of the HH with reminder, 20% MEMS with 18 months, and 100% with 2-year battery life respectively. PMID- 22294892 TI - Reduced fluoresceinamine as a fluorescent sensor for nitric oxide. AB - A new fluorescent sensor for nitric oxide (NO) is presented that is based on its reaction with a non fluorescent substance, reduced fluoresceinamine, producing the highly fluorescent fluoresceinamine. Using a portable homemade stabilized light source consisting of 450 nm LED and fiber optics to guide the light, the sensor responds linearly within seconds in the NO concentration range between about 10-750 MUM with a limit of detection (LOD) of about 1 MUM. The system generated precise intensity readings, with a relative standard deviation of less than 1%. The suitability of the sensor was assessed by monitoring the NO generated by either the nitrous acid decomposition reaction or from a NO releasing compound. Using relatively high incubation times, the sensor also responds quantitatively to hydrogen peroxide and potassium superoxide, however, using transient signal measurements results in no interfering species. PMID- 22294893 TI - A thick-film sensor as a novel device for determination of polyphenols and their antioxidant capacity in white wine. AB - A thick-film electrochemical sensor with an iridium-carbon working electrode was used for determining polyphenols and their antioxidant capacity in white wine. Caffeic acid was used as a model species because it has the ability to produce the highest oxidation current. The correlation coefficient of 0.9975 was obtained between sensor response and caffeic acid content. The total phenolic content (TPC) and scavenging activity on 1,1-diphenyl-2-pycrylhydrazyl (DPPH.) radical were also found to be strongly correlated with the concentration of caffeic acid, with a correlation coefficient of 0.9823 and 0.9958, respectively. The sensor prototype was proven to be a simple, efficient and cost effective device to evaluate the antioxidant capacity of substances. PMID- 22294894 TI - Microfabricated reference electrodes and their biosensing applications. AB - Over the past two decades, there has been an increasing trend towards miniaturization of both biological and chemical sensors and their integration with miniaturized sample pre-processing and analysis systems. These miniaturized lab-on-chip devices have several functional advantages including low cost, their ability to analyze smaller samples, faster analysis time, suitability for automation, and increased reliability and repeatability. Electrical based sensing methods that transduce biological or chemical signals into the electrical domain are a dominant part of the lab-on-chip devices. A vital part of any electrochemical sensing system is the reference electrode, which is a probe that is capable of measuring the potential on the solution side of an electrochemical interface. Research on miniaturization of this crucial component and analysis of the parameters that affect its performance, stability and lifetime, is sparse. In this paper, we present the basic electrochemistry and thermodynamics of these reference electrodes and illustrate the uses of reference electrodes in electrochemical and biological measurements. Different electrochemical systems that are used as reference electrodes will be presented, and an overview of some contemporary advances in electrode miniaturization and their performance will be provided. PMID- 22294895 TI - Chemical sensing using fiber cavity ring-down spectroscopy. AB - Waveguide-based cavity ring-down spectroscopy (CRD) can be used for quantitative measurements of chemical concentrations in small amounts of liquid, in gases or in films. The change in ring-down time can be correlated to analyte concentration when using fiber optic sensing elements that change their attenuation in dependence of either sample absorption or refractive index. Two types of fiber cavities, i.e., fiber loops and fiber strands containing reflective elements, are distinguished. Both types of cavities were coupled to a variety of chemical sensor elements, which are discussed and compared. PMID- 22294896 TI - Improving the ability of image sensors to detect faint stars and moving objects using image deconvolution techniques. AB - In this paper we show how the techniques of image deconvolution can increase the ability of image sensors as, for example, CCD imagers, to detect faint stars or faint orbital objects (small satellites and space debris). In the case of faint stars, we show that this benefit is equivalent to double the quantum efficiency of the used image sensor or to increase the effective telescope aperture by more than 30% without decreasing the astrometric precision or introducing artificial bias. In the case of orbital objects, the deconvolution technique can double the signal-to-noise ratio of the image, which helps to discover and control dangerous objects as space debris or lost satellites. The benefits obtained using CCD detectors can be extrapolated to any kind of image sensors. PMID- 22294897 TI - Cobalt oxide nanosheet and CNT micro carbon monoxide sensor integrated with readout circuit on chip. AB - The study presents a micro carbon monoxide (CO) sensor integrated with a readout circuit-on-a-chip manufactured by the commercial 0.35 MUm complementary metal oxide semiconductor (CMOS) process and a post-process. The sensing film of the sensor is a composite cobalt oxide nanosheet and carbon nanotube (CoOOH/CNT) film that is prepared by a precipitation-oxidation method. The structure of the CO sensor is composed of a polysilicon resistor and a sensing film. The sensor, which is of a resistive type, changes its resistance when the sensing film adsorbs or desorbs CO gas. The readout circuit is used to convert the sensor resistance into the voltage output. The post-processing of the sensor includes etching the sacrificial layers and coating the sensing film. The advantages of the sensor include room temperature operation, short response/recovery times and easy post-processing. Experimental results show that the sensitivity of the CO sensor is about 0.19 mV/ppm, and the response and recovery times are 23 s and 34 s for 200 ppm CO, respectively. PMID- 22294898 TI - Whispering gallery modes in standard optical fibres for fibre profiling measurements and sensing of unlabelled chemical species. AB - Whispering gallery mode resonances in liquid droplets and microspheres have attracted considerable attention due to their potential uses in a range of sensing and technological applications. We describe a whispering gallery mode sensor in which standard optical fibre is used as the whispering gallery mode resonator. The sensor is characterised in terms of the response of the whispering gallery mode spectrum to changes in resonator size, refractive index of the surrounding medium, and temperature, and its measurement capabilities are demonstrated through application to high-precision fibre geometry profiling and the detection of unlabelled biochemical species. The prototype sensor is capable of detecting unlabelled biomolecular species in attomole quantities. PMID- 22294899 TI - Wide dynamic range CMOS potentiostat for amperometric chemical sensor. AB - Presented is a single-ended potentiostat topology with a new interface connection between sensor electrodes and potentiostat circuit to avoid deviation of cell voltage and linearly convert the cell current into voltage signal. Additionally, due to the increased harmonic distortion quantity when detecting low-level sensor current, the performance of potentiostat linearity which causes the detectable current and dynamic range to be limited is relatively decreased. Thus, to alleviate these irregularities, a fully-differential potentiostat is designed with a wide output voltage swing compared to single-ended potentiostat. Two proposed potentiostats were implemented using TSMC 0.18-MUm CMOS process for biomedical application. Measurement results show that the fully differential potentiostat performs relatively better in terms of linearity when measuring current from 500 pA to 10 uA. Besides, the dynamic range value can reach a value of 86 dB. PMID- 22294900 TI - Study of sodium ion selective electrodes and differential structures with anodized indium tin oxide. AB - The objective of this work is the study and characterization of anodized indium tin oxide (anodized-ITO) as a sodium ion selective electrode and differential structures including a sodium-selective-membrane/anodized-ITO as sensor 1, an anodized-ITO membrane as the contrast sensor 2, and an ITO as the reference electrode. Anodized-ITO was fabricated by anodic oxidation at room temperature, a low cost and simple manufacture process that makes it easy to control the variation in film resistance. The anodized-ITO based on EGFET structure has good linear pH sensitivity, approximately 54.44 mV/pH from pH 2 to pH 12. The proposed sodium electrodes prepared by PVC-COOH, DOS embedding colloid, and complex Na TFBD and ionophore B12C4, show good sensitivity at 52.48 mV/decade for 10(-4) M to 1 M, and 29.96 mV/decade for 10(-7) M to 10(-4) M. The sodium sensitivity of the differential sodium-sensing device is 58.65 mV/decade between 10(-4) M and 1 M, with a corresponding linearity of 0.998; and 19.17 mV/decade between 10(-5) M and 10(-4) M. PMID- 22294901 TI - Design of self-oscillating gels and application to biomimetic actuators. AB - As a novel biomimetic polymer, we have developed polymer gels with an autonomous self-oscillating function. This was achieved by utilizing oscillating chemical reactions, called the Belousov-Zhabotinsky (BZ) reaction, which is recognized as a chemical model for understanding several autonomous phenomena in biological systems. Under the coexistence of the reactants, the polymer gel undergoes spontaneous swelling-deswelling changes without any on-off switching by external stimuli. In this review, our recent studies on the self-oscillating polymer gels and application to biomimetic actuators are summarized. PMID- 22294902 TI - Optical fiber sensing based on reflection laser spectroscopy. AB - An overview on high-resolution and fast interrogation of optical-fiber sensors relying on laser reflection spectroscopy is given. Fiber Bragg-gratings (FBGs) and FBG resonators built in fibers of different types are used for strain, temperature and acceleration measurements using heterodyne-detection and optical frequency-locking techniques. Silica fiber-ring cavities are used for chemical sensing based on evanescent-wave spectroscopy. Various arrangements for signal recovery and noise reduction, as an extension of most typical spectroscopic techniques, are illustrated and results on detection performances are presented. PMID- 22294903 TI - Detection of non-amplified Mycobacterium tuberculosis genomic DNA using piezoelectric DNA-based biosensors. AB - Piezoelectric DNA-based biosensor technology was developed as a new method for detection of M. tuberculosis. This method consists of immobilizing a thiol modified oligonucleotide probe on the gold electrode surface of a quartz crystal, using a self-assembled monolayer method. The advantage of this study is that a non-amplified genomic bacterial DNA target was used. Instead, the genomic DNA was digested by restriction enzyme to obtain DNA fragments containing the target sequence. The fabricated biosensor was evaluated through an examination of 200 samples. No cross hybridization were observed against M. avium complex and other microorganisms. This target DNA preparation, without PCR amplification, will reduce time, costs, and the tedious step of amplification. PMID- 22294904 TI - Small fluxgate magnetometers: development and future trends in Spain. AB - In this paper, we give an overview of the research on fluxgate magnetometers carried out in Spain. In particular we focus in the development of the planar type instruments. We summarize the fabrication processes and signal processing developments as well as their use in complex systems and space. PMID- 22294905 TI - Electrical capacitance volume tomography: design and applications. AB - This article reports recent advances and progress in the field of electrical capacitance volume tomography (ECVT). ECVT, developed from the two-dimensional electrical capacitance tomography (ECT), is a promising non-intrusive imaging technology that can provide real-time three-dimensional images of the sensing domain. Images are reconstructed from capacitance measurements acquired by electrodes placed on the outside boundary of the testing vessel. In this article, a review of progress on capacitance sensor design and applications to multi-phase flows is presented. The sensor shape, electrode configuration, and the number of electrodes that comprise three key elements of three-dimensional capacitance sensors are illustrated. The article also highlights applications of ECVT sensors on vessels of various sizes from 1 to 60 inches with complex geometries. Case studies are used to show the capability and validity of ECVT. The studies provide qualitative and quantitative real-time three-dimensional information of the measuring domain under study. Advantages of ECVT render it a favorable tool to be utilized for industrial applications and fundamental multi-phase flow research. PMID- 22294906 TI - Position error compensation via a variable reluctance sensor applied to a Hybrid Vehicle Electric machine. AB - In the automotive industry, electromagnetic variable reluctance (VR) sensors have been extensively used to measure engine position and speed through a toothed wheel mounted on the crankshaft. In this work, an application that already uses the VR sensing unit for engine and/or transmission has been chosen to infer, this time, the indirect position of the electric machine in a parallel Hybrid Electric Vehicle (HEV) system. A VR sensor has been chosen to correct the position of the electric machine, mainly because it may still become critical in the operation of HEVs to avoid possible vehicle failures during the start-up and on-the-road, especially when the machine is used with an internal combustion engine. The proposed method uses Chi-square test and is adaptive in a sense that it derives the compensation factors during the shaft operation and updates them in a timely fashion. PMID- 22294907 TI - Advances in lead-free piezoelectric materials for sensors and actuators. AB - Piezoelectrics have widespread use in today's sensor and actuator technologies. However, most commercially available piezoelectric materials, e.g., Pb [Zr(x)Ti(1 x)] O(3) (PZT), are comprised of more than 60 weight percent lead (Pb). Due to its harmful effects, there is a strong impetus to identify new lead-free replacement materials with comparable properties to those of PZT. This review highlights recent developments in several lead-free piezoelectric materials including BaTiO(3), Na(0.5)Bi(0.5)TiO(3), K(0.5)Bi(0.5)TiO(3), Na(0.5)K(0.5)NbO(3), and their solid solutions. The factors that contribute to strong piezoelectric behavior are described and a summary of the properties for the various systems is provided. PMID- 22294908 TI - A star recognition method based on the Adaptive Ant Colony algorithm for star sensors. AB - A new star recognition method based on the Adaptive Ant Colony (AAC) algorithm has been developed to increase the star recognition speed and success rate for star sensors. This method draws circles, with the center of each one being a bright star point and the radius being a special angular distance, and uses the parallel processing ability of the AAC algorithm to calculate the angular distance of any pair of star points in the circle. The angular distance of two star points in the circle is solved as the path of the AAC algorithm, and the path optimization feature of the AAC is employed to search for the optimal (shortest) path in the circle. This optimal path is used to recognize the stellar map and enhance the recognition success rate and speed. The experimental results show that when the position error is about 50", the identification success rate of this method is 98% while the Delaunay identification method is only 94%. The identification time of this method is up to 50 ms. PMID- 22294909 TI - A comparison of Spectral Angle Mapper and Artificial Neural Network classifiers combined with Landsat TM imagery analysis for obtaining burnt area mapping. AB - Satellite remote sensing, with its unique synoptic coverage capabilities, can provide accurate and immediately valuable information on fire analysis and post fire assessment, including estimation of burnt areas. In this study the potential for burnt area mapping of the combined use of Artificial Neural Network (ANN) and Spectral Angle Mapper (SAM) classifiers with Landsat TM satellite imagery was evaluated in a Mediterranean setting. As a case study one of the most catastrophic forest fires, which occurred near the capital of Greece during the summer of 2007, was used. The accuracy of the two algorithms in delineating the burnt area from the Landsat TM imagery, acquired shortly after the fire suppression, was determined by the classification accuracy results of the produced thematic maps. In addition, the derived burnt area estimates from the two classifiers were compared with independent estimates available for the study region, obtained from the analysis of higher spatial resolution satellite data. In terms of the overall classification accuracy, ANN outperformed (overall accuracy 90.29%, Kappa coefficient 0.878) the SAM classifier (overall accuracy 83.82%, Kappa coefficient 0.795). Total burnt area estimates from the two classifiers were found also to be in close agreement with the other available estimates for the study region, with a mean absolute percentage difference of ~ 1% for ANN and ~ 6.5% for SAM. The study demonstrates the potential of the examined here algorithms in detecting burnt areas in a typical Mediterranean setting. PMID- 22294910 TI - Quantum cascade laser-based photoacoustic spectroscopy for trace vapor detection and molecular discrimination. AB - We report on the development of a microelectromechanical systems (MEMS)-scale photoacoustic sensor for the detection of trace gases. A mid-infrared quantum cascade laser (QCL) was used to determine detection limits for acetic acid, acetone, 1,4-dioxane, and vinyl acetate. The source was continuously tunable from 1015 cm(-1) to 1240 cm(-1), allowing for the collection of photoacoustic vibrational spectra for these gases. Exceptional agreement between the measured photoacoustic spectra and the infrared spectra for acetic acid, acetone, 1,4 dioxane, and vinyl acetate was observed. Partial least-squares (PLS) regression was used to develop an algorithm for classification of these compounds based solely on photoacoustic spectra. PMID- 22294911 TI - Distributed power allocation for sink-centric clusters in multiple sink wireless sensor networks. AB - Due to the battery resource constraints, saving energy is a critical issue in wireless sensor networks, particularly in large sensor networks. One possible solution is to deploy multiple sink nodes simultaneously. Another possible solution is to employ an adaptive clustering hierarchy routing scheme. In this paper, we propose a multiple sink cluster wireless sensor networks scheme which combines the two solutions, and propose an efficient transmission power control scheme for a sink-centric cluster routing protocol in multiple sink wireless sensor networks, denoted as MSCWSNs-PC. It is a distributed, scalable, self organizing, adaptive system, and the sensor nodes do not require knowledge of the global network and their location. All sinks effectively work out a representative view of a monitored region, after which power control is employed to optimize network topology. The simulations demonstrate the advantages of our new protocol. PMID- 22294912 TI - Automatic chessboard detection for intrinsic and extrinsic camera parameter calibration. AB - There are increasing applications that require precise calibration of cameras to perform accurate measurements on objects located within images, and an automatic algorithm would reduce this time consuming calibration procedure. The method proposed in this article uses a pattern similar to that of a chess board, which is found automatically in each image, when no information regarding the number of rows or columns is supplied to aid its detection. This is carried out by means of a combined analysis of two Hough transforms, image corners and invariant properties of the perspective transformation. Comparative analysis with more commonly used algorithms demonstrate the viability of the algorithm proposed, as a valuable tool for camera calibration. PMID- 22294913 TI - Signal amplification by enzymatic reaction in an immunosensor based on localized surface plasmon resonance (LSPR). AB - An enzymatic reaction was employed as a means to enhance the sensitivity of an immunosensor based on localized surface plasmon resonance (LSPR). The reaction occurs after intermolecular binding between an antigen and an antibody on gold nano-island (NI) surfaces. For LSPR sensing, the gold NI surface was fabricated on glass substrates using vacuum evaporation and heat treatment. The interferon gamma (IFN-gamma) capture antibody was immobilized on the gold NIs, followed by binding of IFN-gamma to the antibody. Subsequently, a biotinylated antibody and a horseradish peroxidase (HRP) conjugated with avidin were simultaneously introduced. A solution of 4-chloro-1-naphthol (4-CN) was then used for precipitation; precipitation was the result of the enzymatic reaction catalyzed the HRP on gold NIs. The LSPR spectra were obtained after each binding process. Using this method, the enzyme-catalyzed precipitation reaction on the gold NI surface was found to effectively amplify the change in the signal of the LSPR immunosensor after intermolecular binding. PMID- 22294914 TI - Response Ant Colony Optimization of end milling surface roughness. AB - Metal cutting processes are important due to increased consumer demands for quality metal cutting related products (more precise tolerances and better product surface roughness) that has driven the metal cutting industry to continuously improve quality control of metal cutting processes. This paper presents optimum surface roughness by using milling mould aluminium alloys (AA6061-T6) with Response Ant Colony Optimization (RACO). The approach is based on Response Surface Method (RSM) and Ant Colony Optimization (ACO). The main objectives to find the optimized parameters and the most dominant variables (cutting speed, feedrate, axial depth and radial depth). The first order model indicates that the feedrate is the most significant factor affecting surface roughness. PMID- 22294915 TI - Coverage-guaranteed sensor node deployment strategies for wireless sensor networks. AB - Deployment quality and cost are two conflicting aspects in wireless sensor networks. Random deployment, where the monitored field is covered by randomly and uniformly deployed sensor nodes, is an appropriate approach for large-scale network applications. However, their successful applications depend considerably on the deployment quality that uses the minimum number of sensors to achieve a desired coverage. Currently, the number of sensors required to meet the desired coverage is based on asymptotic analysis, which cannot meet deployment quality due to coverage overestimation in real applications. In this paper, we first investigate the coverage overestimation and address the challenge of designing coverage-guaranteed deployment strategies. To overcome this problem, we propose two deployment strategies, namely, the Expected-area Coverage Deployment (ECD) and BOundary Assistant Deployment (BOAD). The deployment quality of the two strategies is analyzed mathematically. Under the analysis, a lower bound on the number of deployed sensor nodes is given to satisfy the desired deployment quality. We justify the correctness of our analysis through rigorous proof, and validate the effectiveness of the two strategies through extensive simulation experiments. The simulation results show that both strategies alleviate the coverage overestimation significantly. In addition, we also evaluate two proposed strategies in the context of target detection application. The comparison results demonstrate that if the target appears at the boundary of monitored region in a given random deployment, the average intrusion distance of BOAD is considerably shorter than that of ECD with the same desired deployment quality. In contrast, ECD has better performance in terms of the average intrusion distance when the invasion of intruder is from the inside of monitored region. PMID- 22294916 TI - Metal oxide gas sensors: sensitivity and influencing factors. AB - Conductometric semiconducting metal oxide gas sensors have been widely used and investigated in the detection of gases. Investigations have indicated that the gas sensing process is strongly related to surface reactions, so one of the important parameters of gas sensors, the sensitivity of the metal oxide based materials, will change with the factors influencing the surface reactions, such as chemical components, surface-modification and microstructures of sensing layers, temperature and humidity. In this brief review, attention will be focused on changes of sensitivity of conductometric semiconducting metal oxide gas sensors due to the five factors mentioned above. PMID- 22294917 TI - Quantitative determination of fibrinogen of patients with coronary heart diseases through piezoelectric agglutination sensor. AB - Fibrinogen can transform fibrin through an agglutination reaction, finally forming fibrin polymer with grid structure. The density and viscosity of the reaction system changes drastically during the course of agglutination. In this research, we apply an independently-developed piezoelectric agglutination sensor to detect the fibrinogen agglutination reaction in patients with coronary heart diseases. The terminal judgment method of determining plasma agglutination reaction through piezoelectric agglutination sensor was established. In addition, the standard curve between plasma agglutination time and fibrinogen concentration was established to determinate fibrinogen content quantitatively. The results indicate the close correlation between the STAGO paramagnetic particle method and the method of piezoelectric agglutination sensor for the detection of Fibrinogen. The correlation coefficient was 0.91 (gamma = 0.91). The determination can be completed within 10 minutes. The fibrinogen concentration in the coronary heart disease group was significantly higher than that of the healthy control group (P < 0.05). The results reveal that high fibrinogen concentration is closely correlated to the incurrence, development and prognosis of coronary heart diseases. Compared with other traditional methods, the method of piezoelectric agglutination sensor has some merits such as operation convenience, small size, low cost, quick detecting, good precision and the common reacting agents with paramagnetic particle method. PMID- 22294918 TI - Immobilization of acetylcholinesterase on screen-printed electrodes. Application to the determination of arsenic(III). AB - Enzymatic amperometric procedures for measuring arsenic, based on the inhibitive action of this metal on acetylcholinesterase enzyme activity, have been developed. Screen-printed carbon electrodes (SPCEs) were used with acetylcholinesterase covalently bonded directly to its surface. The amperometric response of acetylcholinesterase was affected by the presence of arsenic ions, which caused a decrease in the current intensity. The experimental optimum working conditions of pH, substrate concentration and potential applied, were established. Under these conditions, repeatability and reproducibility of biosensors were determined, reaching values below 4% in terms of relative standard deviation. The detection limit obtained for arsenic was 1.1 * 10(-8) M for Ach/SPCE biosensor. Analysis of the possible effect of the presence of foreign ions in the solution was performed. The method was applied to determine levels of arsenic in spiked tap water samples. PMID- 22294919 TI - Real-time estimation of pathological tremor parameters from gyroscope data. AB - This paper presents a two stage algorithm for real-time estimation of instantaneous tremor parameters from gyroscope recordings. Gyroscopes possess the advantage of providing directly joint rotational speed, overcoming the limitations of traditional tremor recording based on accelerometers. The proposed algorithm first extracts tremor patterns from raw angular data, and afterwards estimates its instantaneous amplitude and frequency. Real-time separation of voluntary and tremorous motion relies on their different frequency contents, whereas tremor modelling is based on an adaptive LMS algorithm and a Kalman filter. Tremor parameters will be employed to drive a neuroprosthesis for tremor suppression based on biomechanical loading. PMID- 22294920 TI - Data driven performance evaluation of Wireless Sensor Networks. AB - Wireless Sensor Networks are presented as devices for signal sampling and reconstruction. Within this framework, the qualitative and quantitative influence of (i) signal granularity, (ii) spatial distribution of sensors, (iii) sensors clustering, and (iv) signal reconstruction procedure are assessed. This is done by defining an error metric and performing a Monte Carlo experiment. It is shown that all these factors have significant impact on the quality of the reconstructed signal. The extent of such impact is quantitatively assessed. PMID- 22294921 TI - Trapped ion oscillation frequencies as sensors for spectroscopy. AB - The oscillation frequencies of charged particles in a Penning trap can serve as sensors for spectroscopy when additional field components are introduced to the magnetic and electric fields used for confinement. The presence of so-called "magnetic bottles" and specific electric anharmonicities creates calculable energy-dependences of the oscillation frequencies in the radiofrequency domain which may be used to detect the absorption or emission of photons both in the microwave and optical frequency domains. The precise electronic measurement of these oscillation frequencies therefore represents an optical sensor for spectroscopy. We discuss possible applications for precision laser and microwave spectroscopy and their role in the determination of magnetic moments and excited state life-times. Also, the trap-assisted measurement of radiative nuclear de excitations in the X-ray domain is discussed. This way, the different applications range over more than 12 orders of magnitude in the detectable photon energies, from below MUeV in the microwave domain to beyond MeV in the X-ray domain. PMID- 22294922 TI - Virtual sensor for failure detection, identification and recovery in the transition phase of a morphing aircraft. AB - The Helicopter Adaptive Aircraft (HADA) is a morphing aircraft which is able to take-off as a helicopter and, when in forward flight, unfold the wings that are hidden under the fuselage, and transfer the power from the main rotor to a propeller, thus morphing from a helicopter to an airplane. In this process, the reliable folding and unfolding of the wings is critical, since a failure may determine the ability to perform a mission, and may even be catastrophic. This paper proposes a virtual sensor based Fault Detection, Identification and Recovery (FDIR) system to increase the reliability of the HADA aircraft. The virtual sensor is able to capture the nonlinear interaction between the folding/unfolding wings aerodynamics and the HADA airframe using the navigation sensor measurements. The proposed FDIR system has been validated using a simulation model of the HADA aircraft, which includes real phenomena as sensor noise and sampling characteristics and turbulence and wind perturbations. PMID- 22294923 TI - Effect of silver annealing conditions on the performance of electrolytic silver/silver chloride electrodes used in Harned cell measurements of pH. AB - We have studied the long and short term stability of electrolytic Ag/AgCl electrodes fabricated from Ag wire that has been subjected to a range of different annealing conditions. At elevated temperatures, the presence of oxygen during the annealing process has been shown to be detrimental to the performance of electrodes produced. This phenomenon has been attributed to the dissolution of oxygen in the Ag lattice leading to structural changes in the Ag/AgCl electrode material. Electrodes prepared from Ag wire annealed in the absence of oxygen have shown no appreciable change in performance throughout the temperature range employed. This work has resulted in an improved understanding of the optimum annealing conditions required for Ag used in the preparation of electrolytic Ag/AgCl reference electrodes. This work has positive implications for the accuracy of Harned cell measurements of pH. PMID- 22294924 TI - A deployment of fine-grained sensor network and empirical analysis of urban temperature. AB - Temperature in an urban area exhibits a complicated pattern due to complexity of infrastructure. Despite geographical proximity, structures of a group of buildings and streets affect changes in temperature. To investigate the pattern of fine-grained distribution of temperature, we installed a densely distributed sensor network called UScan. In this paper, we describe the system architecture of UScan as well as experience learned from installing 200 sensors in downtown Tokyo. The field experiment of UScan system operated for two months to collect long-term urban temperature data. To analyze the collected data in an efficient manner, we propose a lightweight clustering methodology to study the correlation between the pattern of temperature and various environmental factors including the amount of sunshine, the width of streets, and the existence of trees. The analysis reveals meaningful results and asserts the necessity of fine-grained deployment of sensors in an urban area. PMID- 22294925 TI - Efficiency of event-based sampling according to error energy criterion. AB - The paper belongs to the studies that deal with the effectiveness of the particular event-based sampling scheme compared to the conventional periodic sampling as a reference. In the present study, the event-based sampling according to a constant energy of sampling error is analyzed. This criterion is suitable for applications where the energy of sampling error should be bounded (i.e., in building automation, or in greenhouse climate monitoring and control). Compared to the integral sampling criteria, the error energy criterion gives more weight to extreme sampling error values. The proposed sampling principle extends a range of event-based sampling schemes and makes the choice of particular sampling criterion more flexible to application requirements. In the paper, it is proved analytically that the proposed event-based sampling criterion is more effective than the periodic sampling by a factor defined by the ratio of the maximum to the mean of the cubic root of the signal time-derivative square in the analyzed time interval. Furthermore, it is shown that the sampling according to energy criterion is less effective than the send-on-delta scheme but more effective than the sampling according to integral criterion. On the other hand, it is indicated that higher effectiveness in sampling according to the selected event-based criterion is obtained at the cost of increasing the total sampling error defined as the sum of errors for all the samples taken. PMID- 22294926 TI - Organic ISFET based on poly (3-hexylthiophene). AB - We have fabricated organic field-effect transistors (OFETs) with regioregular poly(3-hexylthiophene) (P3HT) operable at low-voltages in liquid solutions, suitable for in vitro biosensing applications. Measurements in electrolytes have shown that the performance of the transistors did not deteriorate and they can be directly used as ion-sensitive transducers. Furthermore, more complex media have been tested, with the perspective of cell analysis. Degradation effects acting on the device operating in liquid could be partly compensated by adopting an alternate current measuring mode. PMID- 22294927 TI - Decentralized sensor fusion for Ubiquitous Networking Robotics in Urban Areas. AB - In this article we explain the architecture for the environment and sensors that has been built for the European project URUS (Ubiquitous Networking Robotics in Urban Sites), a project whose objective is to develop an adaptable network robot architecture for cooperation between network robots and human beings and/or the environment in urban areas. The project goal is to deploy a team of robots in an urban area to give a set of services to a user community. This paper addresses the sensor architecture devised for URUS and the type of robots and sensors used, including environment sensors and sensors onboard the robots. Furthermore, we also explain how sensor fusion takes place to achieve urban outdoor execution of robotic services. Finally some results of the project related to the sensor network are highlighted. PMID- 22294928 TI - Fluorescent silicate materials for the detection of paraoxon. AB - Porphyrins are a family of highly conjugated molecules that strongly absorb visible light and fluoresce intensely. These molecules are sensitive to changes in their immediate environment and have been widely described for optical detection applications. Surfactant-templated organosilicate materials have been described for the semi-selective adsorption of small molecule contaminants. These structures offer high surface areas and large pore volumes within an organized framework. The organic bridging groups in the materials can be altered to provide varied binding characteristics. This effort seeks to utilize the tunable binding selectivity, high surface area, and low materials density of these highly ordered pore networks and to combine them with the unique spectrophotometric properties of porphyrins. In the porphyrin-embedded materials (PEMs), the organosilicate scaffold stabilizes the porphyrin and facilitates optimal orientation of porphyrin and target. The materials can be stored under ambient conditions and offer exceptional shelf-life. Here, we report on the design of PEMs with specificity for organophosphates and compounds of similar structure. PMID- 22294929 TI - An adaptive fault-tolerant event detection scheme for wireless sensor networks. AB - In this paper, we present an adaptive fault-tolerant event detection scheme for wireless sensor networks. Each sensor node detects an event locally in a distributed manner by using the sensor readings of its neighboring nodes. Confidence levels of sensor nodes are used to dynamically adjust the threshold for decision making, resulting in consistent performance even with increasing number of faulty nodes. In addition, the scheme employs a moving average filter to tolerate most transient faults in sensor readings, reducing the effective fault probability. Only three bits of data are exchanged to reduce the communication overhead in detecting events. Simulation results show that event detection accuracy and false alarm rate are kept very high and low, respectively, even in the case where 50% of the sensor nodes are faulty. PMID- 22294930 TI - Refractive index sensor based on a 1D photonic crystal in a microfluidic channel. AB - A refractive index sensor has been fabricated in silicon oxynitride by standard UV lithography and dry etching processes. The refractive index sensor consists of a 1D photonic crystal (PhC) embedded in a microfluidic channel addressed by fiber terminated planar waveguides. Experimental demonstrations performed with several ethanol solutions ranging from a purity of 96.00% (n = 1.36356) to 95.04% (n = 1.36377) yielded a sensitivity (Deltalambda/Deltan) of 836 nm/RIU and a limit of detection (LOD) of 6 * 10(-5) RIU, which is, however, still one order of magnitude higher than the theoretical lower limit of the limit of detection 1.3 * 10(-) (6) RIU. PMID- 22294931 TI - Ambient intelligence systems for personalized sport training. AB - Several research programs are tackling the use of Wireless Sensor Networks (WSN) at specific fields, such as e-Health, e-Inclusion or e-Sport. This is the case of the project "Ambient Intelligence Systems Support for Athletes with Specific Profiles", which intends to assist athletes in their training. In this paper, the main developments and outcomes from this project are described. The architecture of the system comprises a WSN deployed in the training area which provides communication with athletes' mobile equipments, performs location tasks, and harvests environmental data (wind speed, temperature, etc.). Athletes are equipped with a monitoring unit which obtains data from their training (pulse, speed, etc.). Besides, a decision engine combines these real-time data together with static information about the training field, and from the athlete, to direct athletes' training to fulfill some specific goal. A prototype is presented in this work for a cross country running scenario, where the objective is to maintain the heart rate (HR) of the runner in a target range. For each track, the environmental conditions (temperature of the next track), the current athlete condition (HR), and the intrinsic difficulty of the track (slopes) influence the performance of the athlete. The decision engine, implemented by means of (m, s) splines interpolation, estimates the future HR and selects the best track in each fork of the circuit. This method achieves a success ratio in the order of 80%. Indeed, results demonstrate that if environmental information is not take into account to derive training orders, the success ratio is reduced notably. PMID- 22294932 TI - Stress sensors and signal transducers in cyanobacteria. AB - In living cells, the perception of environmental stress and the subsequent transduction of stress signals are primary events in the acclimation to changes in the environment. Some molecular sensors and transducers of environmental stress cannot be identified by traditional and conventional methods. Based on genomic information, a systematic approach has been applied to the solution of this problem in cyanobacteria, involving mutagenesis of potential sensors and signal transducers in combination with DNA microarray analyses for the genome wide expression of genes. Forty-five genes for the histidine kinases (Hiks), 12 genes for serine-threonine protein kinases (Spks), 42 genes for response regulators (Rres), seven genes for RNA polymerase sigma factors, and nearly 70 genes for transcription factors have been successfully inactivated by targeted mutagenesis in the unicellular cyanobacterium Synechocystis sp. PCC 6803. Screening of mutant libraries by genome-wide DNA microarray analysis under various stress and non-stress conditions has allowed identification of proteins that perceive and transduce signals of environmental stress. Here we summarize recent progress in the identification of sensory and regulatory systems, including Hiks, Rres, Spks, sigma factors, transcription factors, and the role of genomic DNA supercoiling in the regulation of the responses of cyanobacterial cells to various types of stress. PMID- 22294933 TI - Dynamical jumping real-time fault-tolerant routing protocol for wireless sensor networks. AB - In time-critical wireless sensor network (WSN) applications, a high degree of reliability is commonly required. A dynamical jumping real-time fault-tolerant routing protocol (DMRF) is proposed in this paper. Each node utilizes the remaining transmission time of the data packets and the state of the forwarding candidate node set to dynamically choose the next hop. Once node failure, network congestion or void region occurs, the transmission mode will switch to jumping transmission mode, which can reduce the transmission time delay, guaranteeing the data packets to be sent to the destination node within the specified time limit. By using feedback mechanism, each node dynamically adjusts the jumping probabilities to increase the ratio of successful transmission. Simulation results show that DMRF can not only efficiently reduce the effects of failure nodes, congestion and void region, but also yield higher ratio of successful transmission, smaller transmission delay and reduced number of control packets. PMID- 22294934 TI - Near-infrared fluorescence detection of acetylcholine in aqueous solution using a complex of rhodamine 800 and p-sulfonatocalix[8]arene. AB - The complexing properties of p-sulfonatocalix[n]arenes (n = 4: S[4], n = 6: S[6], and n = 8: S[8]) for rhodamine 800 (Rh800) and indocyanine green (ICG) were examined to develop a near-infrared (NIR) fluorescence detection method for acetylcholine (ACh). We found that Rh800 (as a cation) forms an inclusion complex with S[n], while ICG (as a twitter ion) have no binding ability for S[n]. The binding ability of Rh800 to S[n] decreased in the order of S[8] > S[6] >> S[4]. By the formation of the complex between Rh800 and S[8], fluorescence intensity of the Rh800 was significantly decreased. From the fluorescence titration of Rh800 by S[8], stoichiometry of the Rh800-S[8] complex was determined to be 1:1 with a dissociation constant of 2.2 MUM in PBS. The addition of ACh to the aqueous solution of the Rh800-S[8] complex caused a fluorescence increase of Rh800, resulting from a competitive replacement of Rh800 by ACh in the complex. From the fluorescence change by the competitive fluorophore replacement, stoichiometry of the Rh800-ACh complex was found to be 1:1 with a dissociation constant of 1.7 mM. The effects of other neurotransmitters on the fluorescence spectra of the Rh800 S[8] complex were examined for dopamine, GABA, glycine, and l-asparatic acid. Among the neurotransmitters examined, fluorescence response of the Rh800-S[8] complex was highly specific to ACh. Rh800-S[8] complexes can be used as a NIR fluorescent probe for the detection of ACh (5 * 10(-4)-10(-3) M) in PBS buffer (pH = 7.2). PMID- 22294935 TI - Cryptanalysis and security improvements of 'two-factor user authentication in wireless sensor networks'. AB - User authentication in wireless sensor networks (WSN) is a critical security issue due to their unattended and hostile deployment in the field. Since sensor nodes are equipped with limited computing power, storage, and communication modules; authenticating remote users in such resource-constrained environments is a paramount security concern. Recently, M.L. Das proposed a two-factor user authentication scheme in WSNs and claimed that his scheme is secure against different kinds of attack. However, in this paper, we show that the M.L. Das scheme has some critical security pitfalls and cannot be recommended for real applications. We point out that in his scheme: users cannot change/update their passwords, it does not provide mutual authentication between gateway node and sensor node, and is vulnerable to gateway node bypassing attack and privileged insider attack. To overcome the inherent security weaknesses of the M.L. Das scheme, we propose improvements and security patches that attempt to fix the susceptibilities of his scheme. The proposed security improvements can be incorporated in the M.L. Das-scheme for achieving a more secure and robust two factor user authentication in WSNs. PMID- 22294936 TI - Karen k. Evans, m.d., samir mardini, m.d., and phillip g. Arnold, m.d. PMID- 22294937 TI - Chest wall reconstruction. PMID- 22294938 TI - Introduction to chest wall reconstruction: anatomy and physiology of the chest and indications for chest wall reconstruction. AB - The chest wall functions as a protective cage around the vital organs of the body, and significant disruption of its structure can have dire respiratory and circulatory consequences. The past several decades have seen a marked improvement in the management and reconstruction of complex chest wall defects. Widespread acceptance of muscle and musculocutaneous flaps such as the latissimus dorsi, pectoralis major, serratus anterior, and rectus abdominis has led to a sharp decrease in infections and mortality. Successful reconstructions are dependent upon a detailed knowledge of the functional anatomy and blood supply of the chest and the underlying pathophysiology of a particular disease process. This article will provide an overview of key principles and evidence-based approaches to chest wall reconstruction. PMID- 22294939 TI - Review of chest wall tumors: a diagnostic, therapeutic, and reconstructive challenge. AB - Chest wall tumors are a heterogeneous group of lesions that provide an interesting diagnostic and therapeutic challenge for surgeons. They make up less than 5% of thoracic malignancies and vary widely in pathology as they arise from all anatomic structures of the chest wall. In general, treatment is wide local excision, the margins for malignant disease are necessarily wider, and adjuvant radiation is typically given for those with positive margins. Chemotherapy is rarely effective. Local control is the most important prognostic factor. Disease free survival for malignant disease is limited by positive margins; therefore full oncologic resection with 4-cm margins should be attempted. For small lesions, the resection and reconstruction is usually straightforward. For more advanced disease or those lesions that require significant functional loss, preoperative planning using a multidisciplinary approach, incorporating thoracic surgery, plastic surgery, neurosurgery, radiation medicine, oncology, and physical medicine and rehabilitation, may be essential. PMID- 22294940 TI - Overview and management of sternal wound infection. AB - Sternal wound infection is a life-threatening complication after cardiac surgery associated with high morbidity and mortality. Past treatment options have included closed suction and continuous irrigation. Current paradigms in the management of sternal wound infection include surgical debridement, vacuum assisted closure therapy, flap coverage, and sternal plating. We provide a general overview of sternal wound infection and treatment options for the plastic surgeon. PMID- 22294941 TI - Stabilization of the chest wall: autologous and alloplastic reconstructions. AB - The goals of chest wall stabilization include maintenance of a rigid airtight cavity, protection of the thoracic and abdominal contents, optimization of respiration, and, whenever possible, an aesthetic reconstruction. Evidence suggests that bony fixation results in reduced ventilator dependence, a shorter overall hospital stay, and improved upper extremity function. We prefer to accomplish this with autologous tissue alone (such as the pectoralis major, latissimus dorsi, or rectus abdominus muscle flaps) for small to moderate defects. En bloc resection of defects larger than 5 cm or containing four or more ribs will likely benefit from chest wall stabilization. For patients previously treated with radiation, even larger defects may be tolerated owing to fibrosis. For these larger defects, methyl methacrylate composite meshes are used and covered with vascularized tissue. Contaminated wounds are generally reconstructed with bioprosthetic mesh rather than synthetic mesh. Using these principles, the reconstructive plastic surgeon can devise a comprehensive and safe plan to repair tremendous defects of the chest wall. PMID- 22294942 TI - Workhorse flaps in chest wall reconstruction: the pectoralis major, latissimus dorsi, and rectus abdominis flaps. AB - Large and life-threatening thoracic cage defects can result from the treatment of traumatic injuries, tumors, infection, congenital anomalies, and radiation injury and require prompt reconstruction to restore respiratory function and soft tissue closure. Important factors for consideration are coverage with healthy tissue to heal a wound, the potential alteration in respiratory mechanics created by large extirpations or nonhealing thoracic wounds, and the need for immediate coverage for vital structures. The choice of technique depends on the size and extent of the defect, its location, and donor site availability with consideration to previous thoracic or abdominal operations. The focus of this article is specifically to describe the use of the pectoralis major, latissimus dorsi, and rectus abdominis muscle flaps for reconstruction of thoracic defects, as these are the workhorse flaps commonly used for chest wall reconstruction. PMID- 22294943 TI - Uncommon flaps for chest wall reconstruction. AB - The omentum, external oblique musculocutaneous, and thoracoepigastric flaps are uncommonly used for chest wall reconstruction. Nevertheless, awareness and knowledge of these flaps is essential for reconstructive surgeons because they fill specific niche indications or serve as lifeboats when workhorse flaps are unavailable. The current report describes the anatomic basis, technical aspects of flap elevation, and indications for these unusual flaps. PMID- 22294944 TI - Microsurgical chest wall reconstruction after oncologic resections. AB - Defect reconstruction after radical oncologic resection of malignant chest wall tumors requires adequate soft tissue reconstruction with function, stability, integrity, and an aesthetically acceptable result of the chest wall. The purpose of this article is to describe possible reconstructive microsurgical pathways after full-thickness oncologic resections of the chest wall. Several reliable free flaps are described, and morbidity and mortality rates of patients are discussed. PMID- 22294945 TI - Management of intrathoracic defects. AB - Intrathoracic defects continue to provide one of the most challenging problems faced by the reconstructive surgeon, particularly in the presence of bronchopleural fistula. We review the principles of management of bronchopleural fistulae and empyema, with an emphasis on the Clagett principle, pedicled and free muscle flaps, and the concept of a "designed air fistula" in bronchopleural fistula management. Although the importance of muscle flap closure in intrathoracic defects is undisputed, the timing and relative superiority of muscle flap closure versus conventional thoracic-surgical techniques remains an unanswered question. PMID- 22294946 TI - Reconstruction of posterior trunk defects. AB - The posterior trunk roughly encompasses the upper back from the shoulders to the lumbar area above the iliac crests. Long-term outcomes in the treatment of defects of the spine and bony thorax have been proved superior if flaps were used. Many local muscle and fasciocutaneous flaps are available alternatives. A guideline, patterned according to arbitrary anatomic territories of the back, is suggested as a starting point for the selection of appropriate primary and secondary flap options. Depending on flap availability, the latissimus dorsi and trapezius muscles are the workhorse flaps for the upper back, whereas perforator flaps have become a useful alternative for the lumbar region in lieu of free flaps. PMID- 22294947 TI - Complications, pitfalls, and outcomes after chest wall reconstruction. AB - Chest wall and mediastinal wounds may be life-threatening. Although modern reconstruction methods with various muscle flaps have reduced morbidity and mortality, chest wall reconstruction presents unique challenges. Major categories of adverse outcomes include (1) persistent infection; (2) interference with respiratory mechanics; (3) functional deficits of the shoulder; and (4) hernias. Persistent infection may be resolved by providing coverage via muscle or omental flap, performing thorough debridement, filling the "dead space" with adequate volume, buttressing repair of visceral fistulae, and covering exposed prosthetic material with vascularized flaps. Potential deficits in respiratory mechanics and shoulder function may be avoided by stabilizing the chest wall skeleton and decreasing donor muscle functional loss. Hernias may be minimized by maintaining visceral "right of domain" to the chest and abdominal cavities. Complex reconstructive cases represent an intricate interplay of physiology, structural protection, and aesthetic considerations and require integration of several management principles. PMID- 22294948 TI - Late complications of chest wall reconstruction: management of painful sternal nonunion. AB - Although rare, sternal nonunion after median sternotomy or traumatic injury is associated with a high rate of morbidity. Pain and sternal clicking are two of the most common complaints and reasons these patients seek evaluation and treatment. Diagnosis of sternal nonunion is based on a thorough history and physical examination and can be confirmed with subsequent radiographic imaging. The treatment for symptomatic sternal nonunion requires stable fixation of the bony fragments and chest wall after the debridement of all nonviable bony and soft tissue by the cardiothoracic or reconstructive surgery team. Multiple fixation techniques have been described and incorporate a wide variety of materials including combinations of wires, cables, pins, bands, staples, and plates. Most recently, several new commercially available plating systems have demonstrated low recurrence and complication rates and resolution of the patient's symptoms on follow-up evaluation. Included in this review are three cases demonstrating the management of symptomatic sternal nonunion using these new techniques and review the history, diagnosis, risk factor, and classification, as well as several of the previously described fixation methods. PMID- 22294949 TI - Management of congenital chest wall deformities. AB - Congenital chest wall deformities are considered to be anomalies in chest wall growth. These can be categorized as either rib cage overgrowth or deformities related to inadequate growth (aplasia or dysplasia). Rib cage overgrowth leads to depression of the sternum (pectus excavatum) or protuberance of the sternum (pectus carinatum) and accounts for greater than 90% of congenital chest wall deformities. The remaining deformities are a result of inadequate growth. Evolution in the management of congenital chest wall deformities has made significant progress over the past 25 years. This article will review chest wall deformities and the current management strategies of these interesting anomalies. PMID- 22294950 TI - Letter from the editor. PMID- 22294951 TI - Postoperative hypoxemia in orthopedic patients with obstructive sleep apnea. AB - Criteria to determine which patients with obstructive sleep apnea (OSA) require intensive postoperative monitoring are lacking. Our postoperative OSA patients are all intensively monitored in the PACU and can provide such data. Thus, we reviewed patient records to determine incidence and risk factors for postoperative hypoxemia in OSA patients and subsequent association with postoperative complications. Five hundred twenty-seven charts of patients with OSA based on preoperative ICD-9 codes were reviewed for outcomes including episodes of hypoxemia and hypercarbia. Univariate analysis, logistic regression, and propensity analysis were performed to determine independent risk factors for hypoxemia and association with adverse outcomes. Thirty-three and 11 percent of these patients developed hypoxemia or hypercarbia. Risk factors for hypoxemia were hypercarbia, home bronchodilator use, BMI >=35, and estimated blood loss >=250 ml. Patients with hypoxemia had significantly more respiratory interventions and increased intensity of care. Patients with hypoxemia had significantly increased length of stay and risk of wound infections. Severe hypoxemia was associated with significantly more interventions than mild hypoxemia. Propensity analysis confirmed significant association of hypoxemia with adverse outcomes after adjustment for pre-existing risk factors. We conclude that postoperative hypoxemia in OSA patients is associated with adverse outcomes. Risk factors for hypoxemia were identified to guide allocation of monitoring resources to high-risk patients. PMID- 22294952 TI - A multimodal clinical pathway can reduce length of stay after total knee arthroplasty. AB - Clinical pathways reduce length of stay which is critical for hospitals to remain financially sound. We sought to determine if a multimodal pathway focusing on pre op discharge planning and pre-emptive pain and nausea management lead to reduced length of stay, better pain management, and more rapid functional gains without an increase in post-op complications. A multimodal pathway incorporating pre-op discharge planning and pre-emptive pain and nausea management was initiated in August of 2007. Physical therapy began the day of surgery. Two hundred eleven patients treated over a 3-month period with the new pathway were compared to 192 patients treated in the last 3 months of an older pathway. Length of stay, VAS scores for pain, and the incidence of nausea were compared. Length of time to achieve functional milestones while in hospital and the incidence of complications out to 6 months were compared. Average length of stay was reduced by 0.26 days. VAS scores for pain were lower. Several functional milestones were achieved earlier and complications were not increased. Efforts to control nausea were not successful and severe nausea was experienced in 40% of patients in both groups. This enhanced pathway can lead to an important reduction in length of stay. Although this reduction seems small, it can significantly increase patient throughput and increase hospital capacity. Post-op nausea continues to be an impediment in patient care after TKR. PMID- 22294953 TI - Initiating physical therapy on the day of surgery decreases length of stay without compromising functional outcomes following total hip arthroplasty. AB - In response to rising health care costs, hospitals are implementing clinical pathways in order to standardize care, improve cost efficiency and outcomes. The purpose of this study was to evaluate the effect of initiating physical therapy (PT) on post operative day 1 (POD1) compared to initiating PT on day of surgery (DOS), on length of stay and in-hospital rehabilitation functional outcomes in total hip arthroplasty patients. This change in PT guidelines was part of the implementation of a new multidisciplinary clinical pathway, adopted by the institution in 2007. A retrospective descriptive study of 408 subjects undergoing unilateral THA compared two groups (204 in each group): those who initiated PT on POD1 and those who initiated PT on DOS. Compared to the POD1 group, patients in the DOS group stayed on average 0.21 days less in the hospital. There was no difference in the achievement of functional milestones in spite of the shortened hospitalization. The initiation of a new clinical pathway was successful in reducing mean length of stay while still allowing patients to achieve all necessary functional outcomes, required for discharge home. PMID- 22294954 TI - A spectral analysis of rotator cuff musculature electromyographic activity: surface and indwelling. AB - Electromyography (EMG) of the shoulder girdle is commonly performed; however, EMG spectral properties of shoulder muscles have not been clearly defined. The purpose of this study was to determine the maximum power frequency, Nyquist rate, and minimum sampling rate for indwelling and surface EMG of the normal shoulder girdle musculature. EMG signals were recorded using indwelling electrodes for the rotator cuff muscles and surface electrodes for ten additional shoulder muscles in ten healthy volunteers. A fast Fourier transform was performed on the raw EMG signal collected during maximal isometric contractions to derive the power spectral density. The 95% power frequency was calculated during the ramp and plateau subphase of each contraction. Data were analyzed with analysis of variance (ANOVA) and paired t tests. Indwelling EMG signals had more than twice the frequency content of surface EMG signals (p < .001). Mean 95% power frequencies ranged from 495 to 560 Hz for indwelling electrodes and from 152 to 260 Hz for surface electrodes. Significant differences in the mean 95% power frequencies existed among muscles monitored with surface electrodes (p = .002), but not among muscles monitored with indwelling electrodes (p = .961). No significant differences in the 95% power frequencies existed among contraction subphases for any of the muscle-electrode combinations. Maximum Nyquist rate was 893 Hz for surface electrodes and 1,764 Hz for indwelling electrodes. Our results suggest that when recording EMG of shoulder muscles, the minimum sampling frequency is 1,340 Hz for surface electrodes and 2,650 Hz for indwelling electrodes. The minimum sampling recommendations are higher than the 1,000 Hz reported in many studies involving EMG of the shoulder. PMID- 22294955 TI - Thromboembolic Complications Following Spine Surgery Assessed with Spiral CT Scans: DVT/PE Following Spine Surgery. AB - Spine surgery is associated with a significant risk of postoperative pulmonary embolism (PE) and/or deep vein thrombosis (DVT). The goal of this study was to determine which symptoms and risk factors were associated with spiral CT scans positive for PE and/or DVT in the postoperative spine surgery patient. We conducted a retrospective review of all spine patients who underwent a postoperative CT to rule out PE during the period of March 2004-February 2006. The type of surgical procedure, risk factors, symptoms prompting scan ordering, anticoagulation, and treatment were recorded. Logistic regression models were used to determine significant predictors of a positive CT in this patient population. Of the 3,331 patients that had spine surgery during the study period, 130 (3.9%) had a spiral CT scan to rule out PE and/or proximal DVT. Thirty-three of the 130 (25.4%) CT scans were positive for PE only, five (3.8%) for PE and DVT, and three (2.3%) for DVT only. Only 24.5% (32) patients had risk factors for thromboembolic disease, and of these, a history of PE and/or DVT was the only significant risk factor for a positive scan (p = 0.03). No presenting symptoms or demographic variables were noted to have a significant association with PE and/or DVT. The type of surgical procedure (i.e., anterior, posterior, and percutaneous) was not associated with an increased risk for PE and/or DVT. Patients who are undergoing spine surgery with a history of thromboembolic disease should be carefully monitored postoperatively and may benefit from more aggressive prophylaxis. PMID- 22294956 TI - Heterotopic bone formation following resurfacing total hip arthroplasty. AB - Heterotopic bone (HO), a rare association with total hip arthroplasty (THA), has recently been shown to be more of a problem with resurfacing hip arthroplasty (RHA). It has been speculated to be the result of greater soft tissue dissection required for this procedure. HO most commonly develops in males and patients with bilateral disease. To better understand if this problem does occur in RHA, groups of patients with RHA on one side and conventional THA on the other were evaluated. We retrospectively identified 45 patients that had RHA on one side and conventional cemented THA on the other. Follow-up has been up to 25 years. HO was graded at every clinical visit using the Brooker Classification. In the RHA group, there were 32 hips without evidence of HO, ten with grade 1, and three with grades 2 or 3. In the THA group, there were 36 hips without any HO, eight with grade 1, and one with grade 2. There was no statistical difference between either types of hip arthroplasty in HO formation overall or in the development of more severe grades. Motion was not significantly affected with the more severe grades. Our data obtained from a bilateral patient model suggests that RHA does not predispose to a greater development of HO. In doing a RHA, one should be aware that there might be an increased likelihood of HO in males with bilateral disease. PMID- 22294957 TI - Anterior cruciate ligament reconstruction using achilles tendon allograft: an assessment of outcome for patients age 30 years and older. AB - Achilles allografts have become popular for anterior cruciate ligament (ACL) reconstructions in older patients. Primary ACL reconstructions using Achilles tendon allografts in patients age 30 years and older are successful in restoring the knee to "normal" or "near normal." During a three-year period, the two senior authors performed 65 primary ACL reconstructions using Achilles tendon allografts in patients aged 30 years and older. Our exclusion criteria were periarticular fracture, ipsilateral/contralateral knee ligament injury, and previous or concomitant osteotomy or cartilage restoration procedure. Each patient was evaluated via physical examination, functional and arthrometric testing, and radiographic and subjective outcome. Knees were considered normal, near normal, or abnormal based on the International Knee Documentation Committee (IKDC) system. Forty-three patients were examined at an average of 33 months (minimum, 24 months) postoperatively. At the time of ACL reconstruction, 35% had normal articular cartilage in all three compartments and 70% had meniscal tears. No re ruptures occurred. While 24% had mean maximal translation differences less than or equal to 3 mm, none had side-to-side differences greater than 5 mm. Postoperative IKDC, Activities of Daily Living, and Activity Rating Scale scores averaged 88, 94, and 7.7, respectively. Despite the overall favorable outcomes, 29% had worsened radiographic grades at follow-up. Using an Achilles allograft for ACL reconstruction in patients older than 30 years, we restored over 90% of knees to normal or near normal while limiting postoperative complications. Poor subjective results may be related less to instability and more to pain, which may result from progressive arthritis. PMID- 22294958 TI - Accessory plantaris muscle: anatomy and prevalence. AB - Accessory and anomalous muscles have been described in humans, but only a few at the level of the knee. The aim of this retrospective cohort analysis was to determine the prevalence of a new accessory muscle located at the level of the knee detected with magnetic resonance imaging (MRI). The accessory muscle is designated an accessory plantaris muscle in this study due to its intimate origin with the normal plantaris muscle. Retrospective review of 1,000 consecutive MRI exams of the knee performed on patients presenting with acute or chronic knee symptoms revealed an accessory plantaris muscle in 63 of the 1,000 patients (6.3%)-38 males (7.5%) and 25 females (5.1%). Origin of 62 of 63 of the accessory plantaris muscles merged with the origin of the normal plantaris muscle, and one of 63 merged with the origin of the lateral head of the gastrocnemius muscle. These accessory plantaris muscles inserted into the iliotibial band, the lateral patellar retinaculum, or the iliotibial tract. PMID- 22294959 TI - The accuracy of an automasking algorithm in plantar pressure measurements. AB - Masking algorithms provide a way to analyze plantar pressure parameters based on distinct anatomical regions of the foot. No study has addressed their accuracy. The purpose of this study was to determine the accuracy of the Novel(r) ten region standard masking algorithm in both dynamic and static measurements in normal feet. Static and dynamic plantar pressure measurements were collected from ten normal subjects (20 ft) with and without 10-mm radiopaque markers placed under the first through fifth metatarsal heads, fifth metatarsal base, and first proximal phalanx. The automask was then applied to subdivide the foot into distinct anatomical areas. Weight-bearing AP radiographs were obtained with and without markers. Plantar pressures and radiographs were overlaid. The percent accuracy of each marker within its appropriate mask region was calculated. The average accuracies of the automasking algorithm regions for dynamic and static measurements, respectively, were 98.8% and 90.4% (1MH), 89.9% and 80.6% (2MH), 98.6% and 81.4% (3MH), 96.8% and 82.3% (4MH), 93.1% and 80.8% (5MH), 97.3% and 92.5% (5MB), and 91.2% and 64.2% (1PPH). Marker presence did not alter foot structure or function as determined by intermetatarsal angles (range, p = 0.361 to p = 0.649) and the center of pressure excursion index (p = 0.727), respectively. The automasking algorithm accurately identifies most foot regions in normal feet, particularly in gait. Such accuracy may be reduced in the setting of foot deformity. Understanding the accuracy of masking algorithms may help guide the interpretation of plantar pressure measurements and ultimately both conservative and operative treatment decisions. PMID- 22294960 TI - Musculoskeletal sonopathology and ultrasound-guided regional anesthesia. AB - The use of real-time ultrasound guidance has revolutionized the practice of regional anesthesia. Ultrasound is rapidly becoming the technique of choice for nerve blockade due to increased success rates, faster onset, and potentially improved safety. In the course of ultrasound-guided regional anesthesia, unexpected pathology may be encountered. Such anomalous or pathological findings may alter the choice of nerve block and occasionally affect surgical management. This case series presents a variety of musculoskeletal conditions that may be encountered during ultrasound-guided regional anesthesia practice. PMID- 22294961 TI - Perioperative management of patients with connective tissue disease. AB - Diseases of the connective tissue are a varied group of disorders with major musculoskeletal manifestations such as joint pain and loss of function. As a consequence of the accompanying inflammatory joint disease, such patients often require surgery. Due to the protean organ-related consequences of these conditions, patients who suffer from chronic connective tissue disease are a highly challenging population in the perioperative context. This paper reviews the management of such patients in this clinical setting. PMID- 22294962 TI - Use of ultrasound in detection and treatment of nerve compromise in a case of humeral lengthening. AB - The development of iatrogenic nerve lesions during and following limb lengthening procedures present a challenge to orthopedic surgeons. Early treatment of nerve damage is critical in salvaging full function of the nerve. Precise location of damage, however, must be determined in order to appropriately administer treatment. We report a patient with a short humerus caused by a growth arrest undergoing a 7-cm lengthening who developed a neurapraxic injury of the radial nerve. Nerve compromise was noted 1 month into the lengthening program. Nerve conduction studies and electromyography could not be used to determine the precise site of injury. Likewise, magnetic resonance imaging and computed tomography were contraindicated and inconclusive, respectively, due to the presence of a metallic external fixation device. High-resolution ultrasonography (US) findings, however, correlated with our clinical examination of the patient's radial nerve function and permitted identification of the precise site of nerve involvement. Treatment was administered by removing a causative half-pin. Several days following treatment, nerve function returned to normal. There are a limited number of articles in the literature regarding nerve injuries associated with limb lengthening and their corrective treatments. The outcome of this case underscores the usefulness of US over various other diagnostic techniques under certain circumstances. PMID- 22294963 TI - Gradual reduction of chronic fracture dislocation of the ankle using ilizarov/taylor spatial frame. AB - With the advances in trauma care, chronic fracture dislocation of the ankle is not a condition commonly seen in modern clinical practice. When encountered, it can be difficult to preserve the ankle joint. We present a case of a 65-year-old female, with a chronic fracture dislocation of the ankle. The ankle joint was subluxated with posterior translation of the talus, displacement of the posterior malleolus fragment, and a distal fibula fracture. A minimally traumatic approach was devised to treat this complex fracture dislocation which included gradual reduction of the ankle with a Taylor spatial frame, followed by stabilization with internal fixation and removal of the frame. Bony union and restoration of the ankle joint congruency was achieved. PMID- 22294964 TI - Percutaneous intradiscal aspiration of a lumbar vacuum disc herniation: a case report. AB - We report a case of an 83-year-old gentleman presenting with acute low back pain and radicular left lower extremity pain after golfing. A magnetic resonance imaging (MRI) of the lumbar spine revealed a low-signal-density lesion compressing the L5 nerve. A computed tomography scan was then ordered, confirming an extra-foraminal disc protrusion at the L5-S1 level, containing a focus of gas that was compressing the left L5 nerve root and communicating with the vacuum disc at L5-S1. After a failed left L5 transforaminal epidural steroid injection, the patient was brought back for a percutaneous intradiscal aspiration of the vacuum disc gas. This resulted in immediate relief for the patient. A follow-up MRI performed 2 months after the procedure found an approximate 25% reduction in the size of the vacuum disc herniation. Six months after the procedure, the patient remains free of radicular pain. This case report suggests that a percutaneous aspiration of gas from a vacuum disc herniation may assist in the treatment of radicular pain. PMID- 22294965 TI - Leiomyoma of the foot: sonographic features with pathologic correlation. AB - Leiomyomas arising outside of the uterus and gastrointestinal tract are uncommon, though these benign soft tissue neoplasms have been reported in the lower extremity and foot. To our knowledge, the sonographic appearance of a lower extremity leiomyoma has not been described in the literature. This report involves a case of leiomyoma of the foot and its sonographic imaging features. MR correlative imaging and histopathology are also provided. PMID- 22294966 TI - Cyclophosphamide responsive interstitial lung disease in "overlap syndrome": a clinical pathology conference held by the division of rheumatology at the hospital for special surgery. PMID- 22294967 TI - Editorial. PMID- 22294968 TI - Risk scores for patients with chest pain: evaluation in the emergency department. AB - Chest pain is a common reason for presentation to the emergency department (ED). Absolute criteria for Acute Coronary Syndrome without ST elevation (NSTE-ACS) are lacking. An acute coronary syndrome (ACS) needs to be distinguished from a variety of other cardiac and non-cardiac diseases that may cause chest pain.For patients with confirmed ACS, several scoring methods can be applied in order to distinguish patients in the coronary care unit who may benefit most from therapies. The PURSUIT, TIMI, GRACE and FRISC risk scores are well validated with this respect. However, none of these risk scores has been used in the identification of an ACS in the emergency setting. The vast majority of patients with chest pain due to causes other than ACS were not evaluated in these trials. An evidence-based systematic stratification and policy for these patients does not currently exist.The more recently developed HEART score is specifically designed to stratify all chest pain patients in the ED. The HEART score was validated in a retrospective multicenter study and proved to be a strong predictor of event free survival on one hand and potentially life threatening cardiac events on the other hand. The HEART score facilitates risk stratification of chest pain patients in the ED. PMID- 22294969 TI - Biobanking in atherosclerotic disease, opportunities and pitfalls. AB - Cardiovascular disease is the leading cause of death in Western countries and current research is still focusing on optimizing therapeutic approaches in the battle against this multifactorial disease. Concepts regarding the pathogenesis of many cardiovascular diseases originate from observations of human atherosclerotic tissue obtained from autopsies or during vascular surgery. These observations have helped us to disentangle the pathophysiology of atherosclerosis. However, identifying vulnerable patients, those prone to developing cardiovascular complications, remains difficult. The search for predictive cardiovascular biomarkers continues and large, well organized biobanks are needed to discover or validate novel biomarkers. Biobanks are an extremely valuable resource that enables us to study the influence of both genetic and environmental factors on the development of multifactorial diseases such as atherosclerosis. This review will focus on the advantages and pitfalls in atherosclerotic biobanking. PMID- 22294970 TI - Is age of 80 years a threshold for carotid revascularization? AB - BACKGROUND AND PURPOSE: Carotid Angioplasty and Stenting (CAS) has emerged as an alternative to Carotid Endarterectomy (CEA) in treatment of carotid stenotic disease. With increasing life expectancy clinicians are more often confronted with patients of higher age. Octogenarians were often excluded from randomized trials comparing CAS to CEA because they were considered high-risk for revascularization. Conflicting results on the peri-procedural outcome of carotid revascularization in these patients have been reported. In order to objectively evaluate whether age above 80 years should be an upper limit for indicating carotid revascularization we systematically reviewed the currently available literature. METHODS: Literature was systematically reviewed between January 2000 and June 2010 using Pubmed and Embase, to identify all relevant studies concerning CAS and CEA in octogenarians. Inclusion criteria were 1) reporting outcome on either CEA or CAS; and 2) data subanalysis on treatment outcome by age. The 30-day Major Adverse Event (MAE) rate (disabling stroke, myocardial infarction or death) was extracted as well as demographic features of included patients. RESULTS: After exclusion of 23 articles, 46 studies were included in this review, 18 involving CAS and 28 involving CEA. A total of 2.963 CAS patients and 14.365 CEA patients with an age >80 years were reviewed. The MAE rate was 6.9% (range 1.6 - 24.0%) following CAS and 4.2% (range 0 - 8.8%) following CEA. A separate analysis in this review included the results of one major registry 140.376 patients) analyzing CEA in octogenarians only reporting on 30-day mortality and not on neurological or cardiac adverse events. When these data were included the MAE following CEA is 2.4% (range 0 - 8.8%) CONCLUSIONS: MAE rates after CEA in octogenarians are comparable with the results of large randomized trials in younger patients. Higher complication rates are described for CAS in octogenarians. In general, age > 80 years is not an absolute cut off point to exclude patients from carotid surgery. In our opinion, CEA should remain the golden standard in the treatment of significant carotid artery stenoses, even in the very elderly. PMID- 22294971 TI - Atherosclerotic plaque biomarkers: beyond the horizon of the vulnerable plaque. AB - Cardiovascular disease (CVD) is the number one cause of death globally, and the majority of CVD is caused by atherosclerosis. Atherosclerosis is a systemic inflammatory disease that leads to myocardial infarction, stroke and lower limb ischemia. Pathological studies have given insight to development of atherosclerosis and the importance of local plaque vulnerability, leading to thrombus formation and cardiovascular events. Due to the burden of cardiovascular disease, identification of patients at risk for cardiovascular events and treatment stratification is needed. The predictive power of classical risk factors is limited, especially in patients with manifest atherosclerosis. Imaging modalities have focused on the characteristics of the vulnerable plaque. However, it has become evident that not all so-called vulnerable plaques lead to rupture and subsequent thrombosis. The latter obviously limits the positive predictive value for imaging assessment of plaques and patients at risk. Serum biomarkers have also been studied extensively, but have very limited application in a clinical setting for risk stratification. In line with the important relation between vulnerable plaques and cardiovascular events, plaque biomarker studies have been initiated. These longitudinal studies are based on the concept, that a vulnerable plaque contains predictive information for future cardiovascular events, also in other territories of the vascular tree. Results look promising and plaque markers can be used to develop imaging modalities to identify patients at risk, or to monitor treatment effect. Plaque biomarker studies do not challenge the definition of the vulnerable plaque, but use its concept in favor of prediction improvement for vascular patients. PMID- 22294972 TI - PLACD-7T Study: Atherosclerotic Carotid Plaque Components Correlated with Cerebral Damage at 7 Tesla Magnetic Resonance Imaging. AB - INTRODUCTION: In patients with carotid artery stenosis histological plaque composition is associated with plaque stability and with presenting symptomatology. Preferentially, plaque vulnerability should be taken into account in pre-operative work-up of patients with severe carotid artery stenosis. However, currently no appropriate and conclusive (non-) invasive technique to differentiate between the high and low risk carotid artery plaque in vivo is available. We propose that 7 Tesla human high resolution MRI scanning will visualize carotid plaque characteristics more precisely and will enable correlation of these specific components with cerebral damage. STUDY OBJECTIVE: The aim of the PlaCD-7T study is 1: to correlate 7T imaging with carotid plaque histology (gold standard); and 2: to correlate plaque characteristics with cerebral damage ((clinically silent) cerebral (micro) infarcts or bleeds) on 7 Tesla high resolution (HR) MRI. DESIGN: We propose a single center prospective study for either symptomatic or asymptomatic patients with haemodynamic significant (70%) stenosis of at least one of the carotid arteries. The Athero Express (AE) biobank histological analysis will be derived according to standard protocol. Patients included in the AE and our prospective study will undergo a pre-operative 7 Tesla HR-MRI scan of both the head and neck area. DISCUSSION: We hypothesize that the 7 Tesla MRI scanner will allow early identification of high risk carotid plaques being associated with micro infarcted cerebral areas, and will thus be able to identify patients with a high risk of periprocedural stroke, by identification of surrogate measures of increased cardiovascular risk. PMID- 22294973 TI - Cardiac autonomic nervous system in heart failure: imaging technique and clinical implications. AB - The autonomic nervous system interacts in the pathophysiology of heart failure. Dysfunction of the sympathetic nervous system has been identified as an important prognostic marker in patients with chronic heart failure. At present, cardiac sympathetic nerve imaging with 123-iodine metaiodobenzylguanidine [123-I MIBG] has been employed most frequently for the assessment of cardiac sympathetic innervation and activation pattern. The majority of studies have shown that cardiac sympathetic dysfunction as assessed with 123-I MIBG imaging is a powerful predictor for heart failure mortality and morbidity. Additionally, 123-I MIBG imaging can be used for prediction of potentially lethal ventricular tachyarrhythmias in heart failure patients. At present however, the lack of standardization of 123-I MIBG imaging procedures represents an evident issue. Standardized criteria on the use of 123-I MIBG imaging will further strengthen the clinical use of 123-I MIBG imaging in heart failure patients. PMID- 22294974 TI - Homeostasis and compensatory homeostasis: bridging Western medicine and traditional chinese medicine. AB - Compensation is a self-protective mechanism in diseases, which may lead to a unique form of homeostasis deviates from that in physiological conditions. The kind of compensatory homeostasis can be embodied as various degrees accompanying disease progression (denoted as compensatory degree). Compensatory homeostasis provides a window for the transition from disease to healthy state. The causes of compensatory homeostasis themselves may be identified as targets for effective measures to eliminate compensation. Compensatory homeostasis embodies significantly mostly in the developing process of chronic diseases, which may help to explain in theory why intensive therapeutic strategies led to unexpected outcome in clinical practice. In addition, a large body of clinical evidence has valued traditional Chinese medicine (TCM), which is based on shifting compensatory homeostasis to the overall human body homeostasis, complementary to Western medicine in the management of chronic disease. In this review, we will briefly summarize the concept of compensation and attempt to bridge Western and traditional Chinese medicine through homeostasis and compensatory homeostasis based on an ample of evidence obtained from both disciplines. PMID- 22294975 TI - Treatment of Heyde's Syndrome by Aortic Valve Replacement. AB - Heyde's syndrome is the association between calcific aortic stenosis and gastrointestinal bleeding due to angiodysplasia. Alterations in von Willebrand factor due to turbulence across the diseased aortic valve have been incriminated in the pathophysiology of this syndrome. Replacement of the aortic valve has been reported to stop the bleeding, but this is debatable. Along with a review of the relevant medical literature, we hereby report a 68 year old patient with aortic stenosis and severe recurrent gastrointestinal bleeding that completely subsided following aortic valve replacement. PMID- 22294976 TI - Anticoagulative strategies in reconstructive surgery--clinical significance and applicability. AB - Advanced strategies in reconstructive microsurgery and especially free tissue transfer with advanced microvascular techniques have been routinely applied and continuously refined for more than three decades in day-to-day clinical work. Bearing in mind the success rates of more than 95%, the value of these techniques in patient care and comfort (one-step reconstruction of even the most complex tissue defects) cannot be underestimated. However, anticoagulative protocols and practices are far from general acceptance and - most importantly - lack the benchmark of evidence basis while the reconstructive and microsurgical methods are mostly standardized. Therefore, the aim of our work was to review the actual literature and synoptically lay out the mechanisms of action of the plethora of anticoagulative substances. The pharmacologic prevention and the surgical intervention of thrombembolic events represent an established and essential part of microsurgery. The high success rates of microvascular free tissue transfer as of today are due to treatment of patients in reconstructive centers where proper patient selection, excellent microsurgical technique, tissue transfer to adequate recipient vessels, and early anastomotic revision in case of thrombosis is provided. Whether the choice of antithrombotic agents is a factor of success remains still unclear. Undoubtedly however the lack of microsurgical experience and bad technique can never be compensated by any regimen of antithrombotic therapy. All the more, the development of consistent standards and algorithms in reconstructive microsurgery is absolutely essential to optimize clinical outcomes and increase multicentric and international comparability of postoperative results and complications. PMID- 22294978 TI - Ubiquitous log odds: a common representation of probability and frequency distortion in perception, action, and cognition. AB - In decision from experience, the source of probability information affects how probability is distorted in the decision task. Understanding how and why probability is distorted is a key issue in understanding the peculiar character of experience-based decision. We consider how probability information is used not just in decision-making but also in a wide variety of cognitive, perceptual, and motor tasks. Very similar patterns of distortion of probability/frequency information have been found in visual frequency estimation, frequency estimation based on memory, signal detection theory, and in the use of probability information in decision-making under risk and uncertainty. We show that distortion of probability in all cases is well captured as linear transformations of the log odds of frequency and/or probability, a model with a slope parameter, and an intercept parameter. We then consider how task and experience influence these two parameters and the resulting distortion of probability. We review how the probability distortions change in systematic ways with task and report three experiments on frequency distortion where the distortions change systematically in the same task. We found that the slope of frequency distortions decreases with the sample size, which is echoed by findings in decision from experience. We review previous models of the representation of uncertainty and find that none can account for the empirical findings. PMID- 22294977 TI - Effects and Mechanisms of 3alpha,5alpha,-THP on Emotion, Motivation, and Reward Functions Involving Pregnane Xenobiotic Receptor. AB - Progestogens [progesterone (P(4)) and its products] play fundamental roles in the development and/or function of the central nervous system during pregnancy. We, and others, have investigated the role of pregnane neurosteroids for a plethora of functional effects beyond their pro-gestational processes. Emerging findings regarding the effects, mechanisms, and sources of neurosteroids have challenged traditional dogma about steroid action. How the P(4) metabolite and neurosteroid, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP), influences cellular functions and behavioral processes involved in emotion/affect, motivation, and reward, is the focus of the present review. To further understand these processes, we have utilized an animal model assessing the effects, mechanisms, and sources of 3alpha,5alpha-THP. In the ventral tegmental area (VTA), 3alpha,5alpha-THP has actions to facilitate affective, and motivated, social behaviors through non-traditional targets, such as GABA, glutamate, and dopamine receptors. 3alpha,5alpha-THP levels in the midbrain VTA both facilitate, and/or are enhanced by, affective and social behavior. The pregnane xenobiotic receptor (PXR) mediates the production of, and/or metabolism to, various neurobiological factors. PXR is localized to the midbrain VTA of rats. The role of PXR to influence 3alpha,5alpha-THP production from central biosynthesis, and/or metabolism of peripheral P(4), in the VTA, as well as its role to facilitate, or be increased by, affective/social behaviors is under investigation. Investigating novel behavioral functions of 3alpha,5alpha-THP extends our knowledge of the neurobiology of progestogens, relevant for affective/social behaviors, and their connections to systems that regulate affect and motivated processes, such as those important for stress regulation and neuropsychiatric disorders (anxiety, depression, schizophrenia, drug dependence). Thus, further understanding of 3alpha,5alpha-THP's role and mechanisms to enhance affective and motivated processes is essential. PMID- 22294980 TI - Trends in qualifying biomarkers in drug safety. Consensus of the 2011 meeting of the spanish society of clinical pharmacology. AB - In this paper we discuss the consensus view on the use of qualifying biomarkers in drug safety, raised within the frame of the XXIV meeting of the Spanish Society of Clinical Pharmacology held in Malaga (Spain) in October, 2011. The widespread use of biomarkers as surrogate endpoints is a goal that scientists have long been pursuing. Thirty years ago, when molecular pharmacogenomics evolved, we anticipated that these genetic biomarkers would soon obviate the routine use of drug therapies in a way that patients should adapt to the therapy rather than the opposite. This expected revolution in routine clinical practice never took place as quickly nor with the intensity as initially expected. The concerted action of operating multicenter networks holds great promise for future studies to identify biomarkers related to drug toxicity and to provide better insight into the underlying pathogenesis. Today some pharmacogenomic advances are already widely accepted, but pharmacogenomics still needs further development to elaborate more precise algorithms and many barriers to implementing individualized medicine exist. We briefly discuss our view about these barriers and we provide suggestions and areas of focus to advance in the field. PMID- 22294979 TI - Tuning the orchestra: transcriptional pathways controlling axon regeneration. AB - Trauma in the adult mammalian central nervous system leads to irreversible structural and functional impairment due to failed regeneration attempts. In contrast, neurons in the peripheral nervous system exhibit a greater regenerative ability. It has been proposed that an orchestrated sequence of transcriptional events controlling the expression of specific sets of genes may be the underlying basis of an early cell-autonomous regenerative response. Understanding whether transcriptional fine tuning, in parallel with strategies aimed at counteracting extrinsic impediments promotes axon re-growth following central nervous system injuries represents an exciting challenge for future studies. Transcriptional pathways controlling axon regeneration are presented and discussed in this review. PMID- 22294981 TI - Prognostic indicators of cardiovascular risk in renal disease. AB - Although the annual mortality rate for end-stage renal disease (ESRD) is decreasing, likely due to an increase in kidney transplantation rate, the survival probability for ESRD patients from day one of dialysis has not changed, and is still poor with a 5-year survival rate of approximately 34%. This is contributed to by a high prevalence of cardiovascular disease, which is the leading cause of death in ESRD patients. In order to improve survival outcomes, patients at high risk of cardiovascular related mortality need to be identified. Heart rate variability (HRV), baroreceptor sensitivity, and baroreceptor reflex effectiveness index can be used to assess heart rate control and may predict cardiovascular mortality. This paper will discuss how HRV, baroreceptor sensitivity, and baroreceptor reflex effectiveness index are altered in renal disease and the utility of these indices as markers of cardiac risk in this patient population. PMID- 22294982 TI - Similar diversity of alphaproteobacteria and nitrogenase gene amplicons on two related sphagnum mosses. AB - Sphagnum mosses represent a main vegetation component in ombrotrophic wetlands. They harbor a specific and diverse microbial community with essential functions for the host. To understand the extend of host specificity and impact of environment, Sphagnum fallax and Sphagnum angustifolium, two phylogenetically closely related species, which show distinct habitat preference with respect to the nutrient level, were analyzed by a multifaceted approach. Microbial fingerprints obtained by PCR-single-strand conformation polymorphism of 16S rRNA and nitrogenase-encoding (nifH) genes were highly similar for both Sphagnum species. Similarity was confirmed for colonization patterns obtained by fluorescence in situ hybridization (FISH) coupled with confocal laser scanning microscopy (CLSM): Alphaproteobacteria were the main colonizers inside the hyaline cells of Sphagnum leaves. A deeper survey of Alphaproteobacteria by 16S rRNA gene amplicon sequencing reveals a high diversity with Acidocella, Acidisphaera, Rhodopila, and Phenylobacterium as major genera for both mosses. Nitrogen fixation is an important function of Sphagnum-associated bacteria, which is fulfilled by microbial communities of Sphagna in a similar way. NifH libraries of Sphagnum-associated microbial communities were characterized by high diversity and abundance of Alphaproteobacteria but contained also diverse amplicons of other taxa, e.g., Cyanobacteria and Deltaproteobacteria. Statistically significant differences between the microbial communities of both Sphagnum species could not be discovered in any of the experimental approach. Our results show that the same close relationship, which exists between the physical, morphological, and chemical characteristics of Sphagnum mosses and the ecology and function of bog ecosystems, also connects moss plantlets with their associated bacterial communities. PMID- 22294983 TI - Extraintestinal Pathogenic Escherichia coli: A Combination of Virulence with Antibiotic Resistance. AB - Escherichia coli represents an incredible versatile and diverse enterobacterial species and can be subdivided into the following; (i) intestinal non-pathogenic, commensal isolates. (ii) Intestinal pathogenic isolates and (iii) extraintestinal pathogenic E. coli or ExPEC isolates. The presence to several putative virulence genes has been positively linked with the pathogenicity of ExPEC. E. coli remains one of the most frequent causes of nosocomial and community-acquired bacterial infections including urinary tract infections, enteric infections, and systemic infections in humans. ExPEC has emerged in 2000s as an important player in the resistance to antibiotics including the cephalosporins and fluoroquinolones. Most importantly among ExPEC is the increasing recognition of isolates producing "newer beta-lactamases" that consists of plasmid-mediated AmpC beta-lactamases (e.g., CMY), extended-spectrum beta-lactamases (e.g., CTX-M), and carbapenemases (e.g., NDM). This review will highlight aspects of virulence associated with ExPEC, provide a brief overview of plasmid-mediated resistance to beta-lactams including the characteristics of the successful international sequence types such as ST38, ST131, ST405, and ST648 among ExPEC. PMID- 22294984 TI - Childhood-Adolescent Obesity in the Cardiorenal Syndrome: Lessons from Animal Models. AB - BACKGROUND/AIMS: Childhood-adolescent overweight and obesity have grown to pandemic proportions during the past decade. The onset of obesity in younger adults will likely be manifested as earlier onset of myocardial and renal end organ disease in younger adults. For the first time, it is estimated that the current generation may not live to be as old as their parents. Thus, it is important to develop animal models of childhood obesity to understand fundamental pathological organ changes. METHODS: In this regard, we utilize transmission electron microscopy evaluation to evaluate early remodeling changes of two adolescent rodent obesity models: the Zucker obese (fa/fa) rat and the db/db mouse models of obesity. We have concentrated on the initial ultrastructural remodeling (obese adipose tissue, skeletal muscle, and islet remodeling) and the associated changes in target end organs (including the myocardium and kidney) in young rodent models of obesity and insulin resistance, collectively manifesting as the cardiorenal metabolic syndrome (CRS). RESULTS: Briefly, tissues revealed the following ultrastructural remodeling abnormalities: inflammation, hypertrophy, and early fibrosis in adipose tissue; loss of mitochondria in skeletal muscles, hyperplasia, fibrosis, and depletion of insulin-secretory granules in pancreatic islets; increased intramyocardial lipid accumulation, fibrosis, and mitochondrial deposition in the myocardium, and obesity-related glomerulopathy and tubulopathy in the kidney. CONCLUSION: Based on the current knowledge and ultrastructural observations of organ pathology, we propose mechanisms whereby obesity appears to be the driving force behind the development of the CRS. PMID- 22294986 TI - How to set the world on fire. PMID- 22294987 TI - Engine or Boat Anchor? The Health Professional Training Establishment in HHR Innovation. AB - Educational institutions have largely failed to provide innovative responses to emerging health human resources (HHR) needs. Reasons include the prevailing ratio policy, which simply increases the supply of professionals; university funding protocols; a guild structure that isolates health professions rather than integrating them; and current credentialing for entry to practice, which both controls and further balkanizes the professions. Providing integrated health services will require (a) embedding interprofessional education and collaborative practice in accreditation requirements, (b) coordinating educational programs via intergovernmental committees and (c) embedding interprofessional collaborative learning in clinical training. PMID- 22294985 TI - Use of Metformin in Patients with Kidney and Cardiovascular Diseases. AB - Metformin is an insulin-sensitizing agent with anti-hyperglycemic properties that is widely used for the treatment of type-2 diabetes. The efficacy of metformin in reducing hyperglycemia is well established, and there is emerging evidence that its chronic use is associated with cancer and cardiovascular disease (CVD) risk reduction. While the hypoglycemic properties of metformin are largely attributed to suppression of hepatic glucose production and increases in peripheral tissue insulin sensitivity, the precise mechanism of the hypoglycemic action of metformin remains unclear. There is evidence that metformin use interrupts mitochondrial oxidative stress in the liver and corrects abnormalities of intracellular calcium metabolism in insulin-sensitive tissues (liver, skeletal muscle, and adipocytes) and cardiovascular tissue. However, the use of metformin in patients with kidney disease, a high-risk CVD state, is confounded by confusion regarding appropriate concerns about the development of lactic acidosis in this population. Thus, we will review current evidence on metformin use for improving CVD outcomes and its therapeutic use in kidney disease. PMID- 22294988 TI - Getting the Foundations Right: Alberta's Approach to Healthcare Reform. AB - Alberta's abolition of its health regions and the creation of Alberta Health Services in 2008 has integrated previously disparate providers of healthcare services. The long-term benefits of this "second-wave" approach to health systems structuring include lower administrative costs, greater equity of access, improved intraprovincial learning and economies of scale. Some benefits have begun to be realized but, as with any merger, performance should be judged over a multi-year time frame. PMID- 22294989 TI - Access to cancer drugs in Canada: looking beyond coverage decisions. AB - OBJECTIVE: To examine variation in patients' access to a set of cancer drugs through publicly funded provincial drug programs. DATA SOURCES/STUDY DESIGN: We surveyed provincial drug program managers about their highest-expenditure intravenous and oral cancer drugs. We then investigated whether the same cancer drugs account for the highest expenditures across the provincial programs. We also compared the rates at which these drugs are accessed through these programs. PRINCIPAL FINDINGS: While there is moderate consistency in the selection of cancer drugs that account for the highest provincial expenditures, considerable differences were found in the rates at which some drugs are accessed across provincial programs. CONCLUSIONS: The study demonstrates the existence of interprovincial variation in publicly funded access to cancer drugs even after these drugs have been approved for public coverage. PMID- 22294990 TI - Geographic accessibility of community pharmacies in ontario. AB - BACKGROUND: Proximity is an important component of access to healthcare services. Recent changes in generic pricing in Ontario have caused speculation about pharmacy closures. However, there is little information on the current geographic accessibility of pharmacies. Therefore, we studied geographic access to pharmacies and modelled the impact of possible closures. METHODS: We used location data on the 3,352 accredited community pharmacies from the Ontario College of Pharmacists and population estimates at the census dissemination block level. Using network analysis, we determined the share of Ontario's population who reside in a census dissemination block within three road travel distances of a community pharmacy: 800 m (walking), 2 km and 5 km (driving). We then simulated the effects on these measures of 10% to 50% reductions in the number of community pharmacies in Ontario. RESULTS: Approximately 63.6% of the Ontario population reside in a dissemination block located within walking distance of one or more pharmacies; 84.6% and 90.7% reside within 2-km and 5-km driving distances, respectively. Randomly removing 30% of Ontario's community pharmacies reduces these estimates to 56.0%, 81.4% and 89.0% for each distance, respectively; a 50% reduction results in 48.3%, 77.1% and 87.2%, respectively. CONCLUSIONS: Pharmacies are geographically accessible for a majority of the Ontario population. Moreover, it appears that modest closures would have only a small impact on geographic access to pharmacies. However, closures may have other impacts on access, such as cost, waiting time and reduced patient choice. PMID- 22294991 TI - Availability of healthcare resources, positive ratings of the care experience and extent of service use: an unexpected relationship. AB - Two main avenues are advocated to improve the capability of healthcare systems to satisfy the public's needs and expectations: more resources and better organization. This paper sheds some light on this debate. It assesses the extent to which patients' positive rating of their healthcare experience and the extent to which they use services are related to the availability of healthcare resources. Findings indicate that patients' evaluations of their care experience and use of services were higher when the availability of resources was either limited or average. In no case were positive ratings of services and greater use of them associated with greater resource availability. Thus, simply adding resources runs the risk of diminishing, rather than improving, users' healthcare experience. PMID- 22294992 TI - Prioritizing information for quality improvement using resident assessment instrument data: experiences in one canadian province. AB - PURPOSE: To elicit priority rankings of indicators of quality of care among providers and decision-makers in continuing care in Alberta, Canada. METHODS: We used modified nominal group technique to elicit priorities and criteria for prioritization among the quality indicators and resident/client assessment protocols developed by the interRAI consortium for use in long-term care and home care. RESULTS: The top-ranked items from the long-term care assessment data were pressure ulcers, pain and incontinence. The top-ranked items from the home care data were pain, falls and proportion of clients at high risk for residential placement. Participants considered a variety of issues in deciding how to rank the indicators. IMPLICATIONS: This work reflects the beginning of a process to better understand how providers and policy makers can work together to assess priorities for quality improvement within continuing care. PMID- 22294993 TI - Predictors of home care expenditures and death at home for cancer patients in an integrated comprehensive palliative home care pilot program. AB - PURPOSE: Empirical understanding of predictors for home care service use and death at home is important for healthcare planning. Few studies have examined these predictors in the context of the publicly funded Canadian home care system. This study examined predictors for home care use and home death in the context of a "gold standard" comprehensive palliative home care program pilot in Ontario where patients had equal access to home care services. METHODS: Secondary clinical and administrative data sources were linked using a unique identifier to examine multivariate factors (predisposing, enabling, need) on total home care expenditures and home death for a cohort of cancer patients enrolled in the HPCNet pilot. RESULTS: SUBJECTS WITH GASTROINTESTINAL SYMPTOMS (OR: 1.64; p=0.03) and those with higher income had increased odds of dying at home (OR: 1.14; p<0.001), whereas age, number of GP visits, gastrointestinal symptoms (i.e., nausea, vomiting, bowel obstruction) and eating problems (i.e., anorexia/cachexia) predicted home care expenditures. CONCLUSIONS: Predictors of home death found in earlier studies appeared less important in this comprehensive palliative home care pilot. An income effect for home death observed in this study requires examination in future controlled studies. RELEVANCE: Access to palliative home care that is adequately resourced and organized to address the multiple domains of issues that patients/families experience at the end of life has the potential to enable home death and shift care appropriately from limited acute care resources. PMID- 22294994 TI - Changes in Physiotherapy Utilization in One Workforce: Implications for Accessibility among Canadian Working-Age Adults. AB - In debates over access to essential medical care, comparatively little attention has been paid to the provision of outpatient physiotherapy services. We examined physiotherapy utilization for musculoskeletal disorders (MSDs) among approximately 2,000 employees of a large, unionized, Ontario workplace. We obtained MSD-related physiotherapy claims and service data from the public Workplace Safety and Insurance Board, two private medical insurance carriers, a workplace special fund starting in 1995 and a workplace-contracted, on-site physiotherapy clinic starting in 1999. We observed substantial increases in overall physiotherapy utilization for MSDs: a median of 234 services per quarter for 1992-1994 to 1,281 for 1999-2002. With inclusive workplace provision policies, most physiotherapy utilization occurred on-site by 1999-2002 (70%). With a user-pay orientation to outpatient physiotherapy services increasing among working-age adults in Ontario, there is substantial potential for unequal access among those not privately insured or in workplaces with direct service provision. PMID- 22294995 TI - Bereavement-related depression in the DSM-5 and ICD-11. PMID- 22294996 TI - Validity of the bereavement exclusion to major depression: does the empirical evidence support the proposal to eliminate the exclusion in DSM-5? AB - The DSM-IV major depression "bereavement exclusion" (BE), which recognizes that depressive symptoms are sometimes normal in recently bereaved individuals, is proposed for elimination in DSM-5. Evidence cited for the BE's invalidity comes from two 2007 reviews purporting to show that bereavement-related depression is similar to other depression across various validators, and a 2010 review of subsequent research. We examined whether the 2007 and 2010 reviews and subsequent relevant literature support the BE's invalidity. Findings were: a) studies included in the 2007 reviews sampled bereavement-related depression groups most of whom were not BE-excluded, making them irrelevant for evaluating BE validity; b) three subsequent studies cited by the 2010 review as supporting BE elimination did examine BE-excluded cases but were in fact inconclusive; and c) two more recent articles comparing recurrence of BE-excluded and other major depressive disorder cases both support the BE's validity. We conclude that the claimed evidence for the BE's invalidity does not exist. The evidence in fact supports the BE's validity and its retention in DSM-5 to prevent false positive diagnoses. We suggest some improvements to increase validity and mitigate risk of false negatives. PMID- 22294997 TI - An attachment perspective on psychopathology. AB - In recent years, attachment theory, which was originally formulated to describe and explain infant-parent emotional bonding, has been applied to the study of adolescent and adult romantic relationships and then to the study of psychological processes, such as interpersonal functioning, emotion regulation, coping with stress, and mental health. In this paper, we offer a brief overview of the attachment perspective on psychopathology. Following a brief account of attachment theory, we go on to explain how the study of individual differences in adult attachment intersects with the study of psychopathology. Specifically, we review research findings showing that attachment insecurity is a major contributor to mental disorders, and that the enhancement of attachment security can facilitate amelioration of psychopathology. PMID- 22294998 TI - Prototype diagnosis of psychiatric syndromes. AB - The method of diagnosing patients used since the early 1980s in psychiatry, which involves evaluating each of several hundred symptoms for their presence or absence and then applying idiosyncratic rules for combining them for each of several hundred disorders, has led to great advances in research over the last 30 years. However, its problems have become increasingly apparent, particularly for clinical practice. An alternative approach, designed to maximize clinical utility, is prototype matching. Instead of counting symptoms of a disorder and determining whether they cross an arbitrary cutoff, the task of the diagnostician is to gauge the extent to which a patient's clinical presentation matches a paragraph-length description of the disorder using a simple 5-point scale, from 1 ("little or no match") to 5 ("very good match"). The result is both a dimensional diagnosis that captures the extent to which the patient "has" the disorder and a categorical diagnosis, with ratings of 4 and 5 corresponding to presence of the disorder and a rating of 3 indicating "subthreshold" or "clinically significant features". The disorders and criteria woven into the prototypes can be identified empirically, so that the prototypes are both scientifically grounded and clinically useful. Prototype diagnosis has a number of advantages: it better captures the way humans naturally classify novel and complex stimuli; is clinically helpful, reliable, and easy to use in everyday practice; facilitates both dimensional and categorical diagnosis and dramatically reduces the number of categories required for classification; allows for clinically richer, empirically derived, and culturally relevant classification; reduces the gap between research criteria and clinical knowledge, by allowing clinicians in training to learn a small set of standardized prototypes and to develop richer mental representations of the disorders over time through clinical experience; and can help resolve the thorny issue of the relation between psychiatric diagnosis and functional impairment. PMID- 22294999 TI - Prototypes, syndromes and dimensions of psychopathology: an open agenda for research. PMID- 22295000 TI - Toward a clinically useful and empirically based dimensional model of psychopathology. PMID- 22295002 TI - Prototypal diagnosis: will this relic from the past become the wave of the future? PMID- 22295001 TI - A practical prototypic system for psychiatric diagnosis: the ICD-11 Clinical Descriptions and Diagnostic Guidelines. PMID- 22295003 TI - Are you as smart as a 4th grader? Why the prototype-similarity approach to diagnosis is a step backward for a scientific psychiatry. PMID- 22295004 TI - Nosological changes in psychiatry: hubris and humility. PMID- 22295005 TI - Prototype diagnosis of psychiatric syndromes and the ICD-11. PMID- 22295006 TI - Prototype matching together with operational criteria would make a better approach to psychiatric classification. PMID- 22295007 TI - Generalizability of the Individual Placement and Support (IPS) model of supported employment outside the US. AB - While reviews of controlled studies of the Individual Placement and Support (IPS) model of supported employment for clients with severe mental illness have documented its effectiveness in the US, its generalizability to other countries has not been systematically evaluated. This is the first review to compare US to non-US studies. We identified 15 randomized controlled trials of IPS programs, 9 in the US and 6 outside the US. We examined competitive employment outcomes, including employment rate, days to first job, weeks worked during follow-up, and hours worked. We also considered noncompetitive employment, program retention, and nonvocational outcomes. IPS programs had significantly better outcomes across a range of competitive employment indicators and higher retention in services than control groups. The overall competitive employment rate for IPS clients in US studies was significantly higher than in non-US studies (62% vs. 47%). The consistently positive competitive employment outcomes strongly favoring IPS over a range of comparison programs in a group of international studies suggest that IPS is an evidence-based practice that may transport well into new settings as long as programs achieve high fidelity to the IPS model, but further research is needed on international adaptations. PMID- 22295008 TI - Age at onset versus family history and clinical outcomes in 1,665 international bipolar-I disorder patients. AB - Early onset in bipolar disorder (BPD) has been associated with greater familial risk and unfavorable clinical outcomes. We pooled data from seven international centers to analyze the relationships of family history and symptomatic as well as functional measures of adult morbidity to onset age, or onset in childhood (age <12), adolescence (12-18), or adulthood (19-55 years). In 1,665 adult, DSM-IV BPD I patients, onset was 5% in childhood, 28% in adolescence, and 53% at peak ages 15-25. Adolescent and adult onset did not differ by symptomatic morbidity (episodes/year, percentage of months ill, co-morbidity, hospitalization, suicide attempts) or family history. Indications of favorable adult functional outcomes (employment, living independently, marriage and children, and a composite measure including education) ranked, by onset: adult > adolescent > child. Onset in childhood versus adolescence had more episodes/year and more psychiatric co morbidity. Family history was most prevalent with childhood onset, similar over onset ages 12-40 years, and fell sharply thereafter. Multivariate modeling sustained the impression that family history and poor functional, but not symptomatic, outcomes were associated with younger, especially childhood onset. Early onset was more related to poor functional outcomes than greater symptomatic morbidity, with least favorable outcomes and greater family history with childhood onset. PMID- 22295009 TI - Lessons learned in developing community mental health care in North America. AB - This paper summarizes the findings for North America of the WPA Task Force on Steps, Obstacles and Mistakes to Avoid in the Implementation of Community Mental Health Care. Community mental health has evolved over five decades in the United States and Canada. The United States has led the world in innovation and spending, but provide variable quality of care; Canada has steadily developed a more uniform public health system for less cost. Lessons learned from North America include: team-based approaches and other evidence-based practices, when implemented with high fidelity, can improve outcomes in routine mental health care settings; recovery ideology and peer support enhance care, though they have not been studied rigorously; effective community-based care for people with serious mental disorders is expensive. PMID- 22295010 TI - Mental health services in the Arab world. AB - This paper summarizes the current situation of mental health services in the Arab world. Out of 20 countries for which information is available, six do not have a mental health legislation and two do not have a mental health policy. Three countries (Lebanon, Kuwait and Bahrain) had in 2007 more than 30 psychiatric beds per 100,000 population, while two (Sudan and Somalia) had less than 5 per 100,000. The highest number of psychiatrists is found in Qatar, Bahrain and Kuwait, while seven countries (Iraq, Libya, Morocco, Somalia, Sudan, Syria and Yemen) have less than 0.5 psychiatrists for 100,000 population. The budget allowed for mental health as a percentage from the total health budget, in the few countries where information is available, is far below the range to promote mental health services. Some improvement has occurred in the last decade, but the mental health human resources and the attention devoted to mental health issues are still insufficient. PMID- 22295011 TI - The crisis of psychiatry - insights and prospects from evolutionary theory. PMID- 22295012 TI - Neurophysiology of a possible fundamental deficit in schizophrenia. PMID- 22295013 TI - Guidance on how to combat stigmatization of psychiatry and psychiatrists. PMID- 22295014 TI - Stigma blocks recovery from mental illness. PMID- 22295016 TI - Papers and documents available on the WPA website. PMID- 22295017 TI - The new WPA leadership. PMID- 22295018 TI - Pharmaceutical market and health system in the Middle Eastern and Central Asian countries: Time for innovations and changes in policies and actions. PMID- 22295020 TI - Neonatal ventilatory techniques - which are best for infants born at term? AB - Few studies have examined ventilatory modes exclusively in infants born at term. Synchronous intermittent mandatory ventilation (SIMV) compared to intermittent mandatory ventilation (IMV) is associated with a shorter duration of ventilation. The limited data on pressure support, volume targeted ventilation and neurally adjusted ventilatory assist demonstrate only short term benefits in term born infants. Favourable results of high-frequency oscillatory ventilation (HFOV) in infants with severe respiratory failure were not confirmed in the two randomised trials. Nitric oxide (NO) in term born infants, except in those with congenital diaphragmatic hernia (CDH), reduces the combined outcome of death and requirement for extracorporeal membrane oxygenation (ECMO). In infants with severe refractory hypoxaemic respiratory failure, ECMO, except in infants with CDH, reduced mortality and the combined outcome of death and severe disability at long-term follow-up. Randomised studies with long term outcomes are required to determine the optimum modes of ventilation in term born infants. PMID- 22295021 TI - A preliminary study on progesterone antioxidation in promoting learning and memory of young ovariectomized mice. AB - INTRODUCTION: The aim of this preliminary study was to evaluate the effect of long-term progesterone (P4) treatment on structural and functional deficits associated with the hippocampus. MATERIAL AND METHODS: Mice served as sham controls or were bilaterally ovariectomized (Ovx), and a 90-day regimen of placebo or P4 was applied to the animal. After the administration, the acquisition and retrieval of mice in contextual fear conditioning (CFC) and a water maze were examined. Hippocampal tissues from some mice in each group were stained with cresyl violet, and the remainder were taken for determining the antioxidant power. RESULTS: Compared with placebo controls, the time spent on freezing was higher and the latencies were longer for mice given high-dose P4 (HP) (p < 0.05) in CFC, and the HP group also had longer searching time spent in the target quadrant (p < 0.05) in the water maze. Compared with placebo controls, the cell number of hippocampus CA1, CA3 and DG was significantly higher in the HP group (p < 0.05), and the thickness of the cell layer in CA1 and DG was also higher in the HP group (p < 0.05). All the oxidative stress biomarkers show that the antioxidative activity in hippocampus tissue from the HP and LP groups is higher than that in placebo controls (p < 0.05). CONCLUSIONS: Ovx impairs learning and memory of mice, which can be rescued by a long-term regimen of HP via its antioxidant effects. PMID- 22295019 TI - Environmental pathways to autoimmune diseases: the cases of primary biliary cirrhosis and multiple sclerosis. AB - The pathways leading to autoimmunity remain enigmatic despite numerous lines of experimental inquiry and epidemiological evidence. The mechanisms leading to the initiation and perpetuation of specific diseases such as primary biliary cirrhosis (PBC) or multiple sclerosis (MS) remain largely enigmatic, although it is established that a combination of genetic predisposition and environmental stimulation is required. The growing number of genome-wide association studies and the largely incomplete concordance for autoimmune diseases in monozygotic twins concur to support the role of the environment (including infectious agents and chemicals) in the breakdown of tolerance leading to autoimmunity through different mechanisms. In the present article we illustrate the current hypotheses related to an environmental impact on the onset of PBC and MS as two representative conditions investigated with complementary approaches. Indeed, while a role of post-translational antigen modifications has been proposed for MS, this field remain unexplored in PBC where, conversely, most evidence is gathered from geoepidemiology and experimental data on xenobiotics or infectious agents. PMID- 22295022 TI - Co-blockade of mecR1/blaR1 signal pathway to restore antibiotic susceptibility in clinical isolates of methicillin-resistant Staphylococcus aureus. AB - INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is caused by the production of low-affinity penicillin-binding protein 2a and beta-lactamases, which are encoded by mecA and blaZ, respectively. Expressions of the two key genes are mutually regulated by MecI and BlaI. The aim of this study was to design specific anti-mecR1 and anti-blaR1 deoxyribozymes and identify the restoration of susceptibility in MRSA isolates with mecI or blaI or no deletions by interfering with the mutual regulation of mecA and blaZ. MATERIAL AND METHODS: Specific deoxyribozymes were designed by using the program RNA structure 4.6. RNA substrates were obtained by transcription in vitro and used to assess the target cleavage of DNAzymes. Transcription of mecR1-mecA and blaR1-blaZ was analysed by real time RT-PCR. The susceptibility of MRSA was tested. RESULTS: Specific deoxyribozymes showed efficient catalytic activity to each own substrate mecR1 or blaR1 in vitro and caused the reduction of mecR1 and blaR1 transcription in vivo. Furthermore, simultaneous administration of two DNAzymes to knockdown mecR1 and blaR1 resulted in increased susceptibility of all MRSA strains tested in this study. CONCLUSIONS: These results demonstrated that combined use of the two specific phosphorothioate deoxyribozymes could be a viable and promising strategy to restore the susceptibility of almost all MRSA clinical isolates. PMID- 22295023 TI - 385 C/A polymorphism of the fatty acid amide hydrolase gene is associated with metabolic syndrome in the Chinese Han population. AB - INTRODUCTION: The endocannabinoid system participates in food intake, energy balance and lipid and glucose metabolism. The biological effects of cannabinoids are limited by the activation of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH). This study aims to analyse whether 385 C/A polymorphism of FAAH is associated with metabolic syndrome (MetS) in the Chinese Han population. MATERIAL AND METHODS: A total of 112 subjects at risk for MetS and 80 healthy controls from Fuzhou, China were genotyped for 385 C/A polymorphism of FAAH using TaqMan assay. Anthropometric measurements and biochemical assessments such as BMI, waist circumference, blood pressure, serum triglycerides (TG), serum total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and plasma insulin levels were performed. RESULTS: CA and AA genotypes of FAAH had higher incidence in MetS subjects than in control subjects. CA and AA genotypes of FAAH in subjects with MetS had relatively elevated levels of waist circumference, body mass index, homeostasis model assessment of insulin resistance (HOMA-IR) and serum triglycerides, and lowered level of high-density lipoprotein cholesterol (HDL-c) compared with CC genotype in MetS subjects. CONCLUSIONS: Results suggest that 385 C/A polymorphism of the FAAH gene may confer an increased risk of MetS in the Chinese Han population. PMID- 22295024 TI - Relevance of I-BMIPP delayed scintigraphic imaging for patients with angina pectoris - a pilot study. AB - INTRODUCTION: The study was designed to clarify the role of (123)I-beta-methyl iodophenylpentadecanoic acid ((123)I-BMIPP) in the evaluation of myocardial fatty acid metabolism in patients with stable angina pectoris (AP) before and after percutaneous coronary intervention (PCI). MATERIAL AND METHODS: TEN CONTROLS (MEAN AGE: 70.4 +/-10.5 years) and 12 patients with AP (mean age: 67.4 +/-11.6 years) and single vessel coronary artery disease participated in the radionuclide cardiac study. Scintigraphic images were acquired at 30 min and at 4 h after (123)I-BMIPP injection to determine early and delayed BMIPP uptake, respectively. The heart-to-mediastinum (H/M) ratio and the washout rate (WR) were calculated from the planar images. All patients underwent scintigraphy one day before PCI and again 1 month after successful PCI. RESULTS: NO SIGNIFICANT DIFFERENCES IN THE EARLY OR DELAYED H/M RATIOS WERE OBSERVED BETWEEN THE PATIENTS AND THE CONTROLS BEFORE PCI (EARLY: 2.70 +/-0.36 vs. 2.73 +/-0.57; delayed: 2.26 +/-0.33 vs. 2.40 +/-0.43; p > 0.2 for both). The early and delayed H/M ratios remained unchanged with the comparison with before PCI (early: 2.72 +/-0.27, delayed: 2.23 +/-0.22; p > 0.2 for both). The global WR before PCI was significantly higher in the patients than in the control group (36.7 +/-9.3%, vs. 28.1 +/-8.2%, p = 0.02). However, the WR after PCI did not significantly differ between the patients and the controls (34.3 +/-7.8% vs. 28.1 +/-8.2%, p = 0.1). CONCLUSIONS: These data may suggest that the WR of (123)I-BMIPP determined from the planar images enhances the presence of myocardial ischaemia. PMID- 22295025 TI - Effect of atorvastatin therapy on borderline vulnerable lesions in patients with acute coronary syndrome. AB - INTRODUCTION: It is still controversial whether borderline lesions with a vulnerable plaque should be stented early or simply treated pharmacologically. No data exist concerning the potential effects of statin therapy on borderline vulnerable lesions in patients with acute coronary syndrome (ACS). MATERIAL AND METHODS: Fifty patients with ACS whose culprit lesions were classified as "borderline lesions" were enrolled. All patients were treated with atorvastatin (20 mg) for 12 months. Intravascular ultrasound (IVUS) was performed and matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and high-sensitive C-reactive protein (hsCRP) levels were measured at baseline and 12-month follow-up. RESULTS: At 12-month follow-up, we found: 1) IVUS revealed that minimal lumen cross-sectional area (CSA) increased but plaque/media (P&M) area and plaque burden decreased. A total of 25 soft plaques (50%) were transformed into fibrous plaques. 2) ApoB, MMP-9 and hsCRP levels decreased, but TIMP-1 level increased. 3) Stepwise multivariate linear regression analysis showed that the independent predictors for changes in P&M area/year were the decrease in MMP-9 and hsCRP levels. CONCLUSIONS: Atorvastatin therapy stabilized borderline vulnerable plaques and reversed atherosclerosis progression in patients with ACS. Reversal of this progression was accompanied by a decrease in the levels of plasma MMP-9 and hsCRP. Changes in MMP-9 and hsCRP could predict vulnerable plaque stabilization. PMID- 22295026 TI - VAMP-8 gene variant is associated with increased risk of early myocardial infarction. AB - INTRODUCTION: Single nucleotide polymorphism in the 3' untranslated region of the vesicle-associated membrane protein gene (VAMP-8) has been associated with increased risk of early-onset myocardial infarction (MI). In this study the risk of early onset MI conferred by VAMP-8 gene polymorphism was investigated in a group of 171 male subjects. MATERIAL AND METHODS: Male patients with a history of MI who underwent coronary angiography were enrolled and divided into early (incident < 55 years of age) and late (incident >= 55 years of age) MI onset groups. Apart from the RFLP-PCR based analysis of the VAMP-8 variant, history of hypertension, lipid abnormalities, smoking and body mass index were recorded. In statistical analyses odds ratios and relative risk were used as a measure of genotype-MI association while logistic regression was implemented for evaluation of MI risk factor strength. RESULTS: VAMP-8 A allele frequency proved to be significantly higher in the early-onset MI group and conferred higher relative risk of early MI in the investigated cohort, when calculated for the individual A allele (p = 0.029). In logistic regression analyses no association between risk genotypes and traditional risk factors was observed. CONCLUSIONS: In this study VAMP-8 A variant was identified as a risk allele for early MI in male subjects. PMID- 22295027 TI - Plasma asymmetric dimethylarginine predicts restenosis after coronary angioplasty. AB - INTRODUCTION: Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of endothelial nitric oxide synthase. Asymmetric dimethylarginine may influence the process of restenosis after coronary angioplasty. The aim of the study was to determine if initial plasma ADMA level could predict restenosis after coronary angioplasty and stenting. MATERIAL AND METHODS: The study group consisted of 60 consecutive patients (10 women and 50 men, average age 58.9 +/ 10.4 years old), who underwent percutaneous coronary angioplasty with bare metal stenting for stable coronary artery disease. All patients underwent follow-up coronary angiography after a 6-month period. Patients were divided into two groups, one with restenosis (n = 22), and the other one without restenosis (n = 38). In addition to measuring acknowledged restenosis risk factors, plasma ADMA level was measured before initial angiography. RESULTS: Asymmetric dimethylarginine plasma level was significantly higher in the group with restenosis than in the group without restenosis (1.94 +/-0.94 umol/l vs. 0.96 +/ 0.67 umol/l; p < 0.05). L-arginine/ADMA ratio was also decreased in the group with restenosis, when compared with the group without restenosis (p < 0.05). Multivariate logistic regression revealed that independent restenosis risk factors were characterised by an initially high ADMA level (p < 0.01), advanced age (p < 0.05) and low level of HDL cholesterol (p < 0.05). CONCLUSIONS: Pre procedural elevated plasma ADMA level increases the risk of restenosis in patients who underwent coronary angioplasty and stenting with bare metal stents. PMID- 22295028 TI - Relationship between B-type natriuretic peptide serum level, echocardiographic TEI index and the degree of diastolic dysfunction in patients with heart failure with preserved systolic function. AB - INTRODUCTION: The growing number of heart failure (HF) patients is becoming an important issue in cardiology. B-type natriuretic peptide (BNP) is a recognized marker of HF, including in patients with preserved systolic function. The TEI index is an indicator of left ventricular function. The aim of the study was to evaluate the relationship between BNP serum level, TEI index and the degree of diastolic dysfunction in patients with HF symptoms and preserved systolic function. MATERIAL AND METHODS: Hundred patients with arterial hypertension and preserved systolic function were enrolled in the study. The study group consisted of 51 individuals with impaired diastolic function and HF symptoms. Fourty-nine hypertensive individuals without HF symptoms were assigned to the control group. B-type natriuretic peptide and echocardiographic examination were performed. Patients were divided into 4 subgroups - with normal diastolic function, impaired relaxation, pseudonormalization and restriction. RESULTS: Median value of BNP in patients with normal diastolic function was 28.36 pg/ml, 87.10 pg/ml in patients with impaired relaxation, 212.75 pg/ml and 461.56 pg/ml in the pseudonormalization and restriction group respectively (p < 0.0001). The median value of the TEI index was: 0.386 in patients with normal diastolic function, 0.507 in individuals with impaired relaxation, 0.639 and 0.725 in the pseudonormalization and restriction group respectively. All the differences were statistically significant (p < 0.0001). A significant positive correlation (r = 0.80, p < 0.001) between BNP and the TEI index was found. CONCLUSIONS: In hypertensive patients with HF symptoms and preserved left ventricular systolic function a highly significant increase in BNP serum level and in the TEI index values related to the deterioration of diastolic dysfunction was found. PMID- 22295029 TI - Predicting lymph node status in patients with early gastric carcinoma using double contrast-enhanced ultrasonography. AB - INTRODUCTION: Double contrast-enhanced ultrasonography (DCUS) is a new method we used in predicting lymph node metastasis (LNM) in patients with early gastric cancer. MATERIAL AND METHODS: Seventy-six patients with early gastric cancer diagnosed by gastroscope and confirmed by pathology after operation were examined using DCUS preoperatively. Group N1 included 15 patients with LNM and group N0 61 patients without LNM. RESULTS: In group N1, 13 patients (87%) had marked hyperenhancement during early arterial phase using DCUS, and 2 patients (13%) were unmarked as hyperenhancement. In group N0, 24 patients (39%) had marked hyperenhancement during early arterial phase using DCUS, and 37 patients (61%) had unmarked hyperenhancement. The sensitivity and specificity of marked hyperenhancement in predicting LNM in patients with early gastric cancer was 86.7% and 60.7% respectively, and the Youden's index was 0.474. The kappa value of this method was 0.89. CONCLUSIONS: Double contrast-enhanced ultrasonography is a new valuable method to evaluate LNM at an early stage of gastric cancer and prognosis of early gastric cancer preoperatively. PMID- 22295030 TI - Evaluation of the neuroprotective effect of dextromethorphan in the acute phase of ischaemic stroke. AB - INTRODUCTION: Stroke is the second leading cause of death in the world. However, there is still no approved neuroprotective drug for acute ischaemic stroke. To clarify the neuroprotective efficacy and safety of dextromethorphan in stroke, the following study was carried out. MATERIAL AND METHODS: Forty patients with acute stroke causing moderate deficit were randomized to be treated with either dextromethorphan 300 mg per day or placebo for 5 days. Plasma level of dextromethorphan and its active metabolite was not evaluated in this study. The NIHSS score was calculated on day 5 and the Barthel activities of daily living index and Rankin score were checked after 3 months by a blinded investigator. Collected data were analysed using the t-test and chi(2) test. RESULTS: In the dextromethorphan-treated group, the mean NIHSS score was 16.8 +/-3.9 at baseline, and was 14.2 +/-4.8 for the placebo-treated group (p = 0.069). At day 5, there was also no significant difference regarding NIHSS score (p = 0.167). At the 3 month follow-up, there was no significant difference regarding Barthel scale and Rankin score between the dextromethorphan and placebo groups. CONCLUSIONS: The results of our study suggest that although low-dose and short-term oral administration of dextromethorphan seems to be not neuroprotective, it does not worsen either patients' condition or NIHSS score. Moreover, patients treated with dextromethorphan showed a significant reduction in seizures (complication after stroke), but had increased chance of MI and renal failure by almost 5% when compared to the placebo-treated groups. More prolonged studies with a higher number of cases are recommended. PMID- 22295031 TI - The effect of GnRH analogues for pituitary suppression on ovarian response in repeated ovarian stimulation cycles. AB - INTRODUCTION: Ovarian stimulation is employed in assisted reproduction techniques in order to obtain as many oocytes as possible. The early rise in oestradiol levels may lead to the premature end of the respective cycle. In order to avoid such an effect, pituitary suppression has been employed. The aim of this study was to evaluate whether maintenance or replacement of the type of GnRH analogue (i.e., agonist or antagonist) employed for pituitary suppression in the consecutive intracytoplasmic sperm injection (ICSI) cycle would negatively influence oocyte quality and ICSI outcome. MATERIAL AND METHODS: A retrospective observational study was conducted including 181 women with primary infertility. Patients were divided into four different groups according to the GnRH analogue used for pituitary suppression in the first and consecutive cycle. RESULTS: When a GnRH agonist was employed for pituitary suppression in the first cycle, the consecutive cycle showed comparable outcomes when performed with either a GnRH agonist or a GnRH antagonist. When the first cycle was performed with a GnRH antagonist, the use of the GnRH agonist in the successive cycle led to an increased number of oocytes retrieved (7.5% vs. 10.3%, p = 0.032) and the production of a higher number of embryos (4.5% vs. 6.3%, p = 0.036). CONCLUSIONS: When the first cycle is carried out with a GnRH antagonist, the use of a GnRH agonist in the successive cycle would lead to increased numbers of oocytes collected and embryos produced. PMID- 22295032 TI - Quality of life in postmenopausal women with reduced bone mineral density: psychometric evaluation of the Polish version of QUALEFFO-41. AB - INTRODUCTION: Evaluation of the quality of life of patients with osteoporosis concerns the physical, emotional, social and pain quality of life domains. The aim of the research was to describe the psychometric properties of the Polish version of QUALEFFO-41 in 253 Polish postmenopausal women with osteopenia or osteoporosis and in 132 postmenopausal women with normal BMD. MATERIAL AND METHODS: The internal reliability of QUALEFFO-41 was studied using Cronbach's alpha coefficient. The reproducibility of the QUALEFFO-41 scales was assessed using Pearson's correlation. The capacity of questions to discriminate between women with reduced bone mineral density (BMD) and normal subjects was assessed by conditional logistic regression to derive an odds ratio with 95% confidence intervals. The discriminative power, which measures the ability of the questionnaire to discriminate between patients, was assessed by clinical validity. Additionally, receiver operating characteristic (ROC) curves were constructed to assess the ability of QUALEFFO-41. RESULTS: Cronbach's alpha coefficient reflecting the reliability and repeatability of the instrument for all domains was satisfactory. Results of scores for domains of QUALEFFO-41 and the score for total QUALEFFO-41 demonstrate a significant difference (p < 0.001) among all groups; only in the case of the pain domain was there a significant difference at the level of p < 0.01 between normal subjects and osteoporotic patients. Receiver operating characteristic curve analysis demonstrated a good discriminating capacity of individual domains and total QUALEFFO-41 score. CONCLUSIONS: The Polish version of QUALEFFO-41 can be used among patients with reduced BMD compared to normal subjects, independently of vertebral fractures, as it is coherent and discriminates well between women with reduced BMD and normal subjects. PMID- 22295033 TI - The effect of breast-feeding duration on bone mineral density in postmenopausal Turkish women: a population-based study. AB - INTRODUCTION: In the present study, we investigated the effects of breast-feeding time on bone mineral density (BMD) later in life. MATERIAL AND METHODS: The current study was based on a retrospective analysis of 586 postmenopausal women with a mean age of 60.8 years, who were screened for osteoporosis by dual energy X-ray absorptiometry (DXA).They were classified into 4 groups with respect to the duration of their breast-feeding as never (group 1), 1-24 months (group 2), 25-60 months (group 3), or > 60 months (group 4). Bone mineral density results for the femur neck and lumbar spine were classified into 3 groups according to WHO criteria as normal (T score > -1.0 SD), osteopenia (T score -1.0 to -2.5 SD), and osteoporosis (T score < -2.5 SD). Patients with osteopenia or osteoporosis (T score < -1.0 SD) were considered as having low bone mass (LBM). RESULTS: We found a correlation between duration of lactation and femur BMD or spine BMD in the study population (r = 0.116, p < 0.005; r = -0.151, p = 0.001, respectively). Significant differences were found between femur BMD and spine BMD of groups in one-way ANOVA analysis (p = 0.025, p = 0.005, respectively). Additionally, when compared with the other three groups, group 4 was older and had longer duration of menopause (p < 0.01). In logistic regression analysis, age and body mass index were found as independent risk factors of LBM [odds ratio: 1.084 (95% CI 1.031 1.141); odds ratio: 0.896 (95% CI 0.859-0.935)], while duration of lactation was not found as an independent predictor of LBM. CONCLUSIONS: In this study, we have found that changes of bone metabolism during lactation had no effect on postmenopausal BMD measured by DXA. Consequently, it can be suggested that long breast-feeding duration is not a risk factor for low bone mass later in life. PMID- 22295034 TI - A long-term study of bone mineral density in patients with phenylketonuria under diet therapy. AB - INTRODUCTION: Dietary control of classic phenylketonuria (PKU) needs restriction of natural proteins; adequate protein intake is achieved by adding low phenylalanine (phe) formulae. The adequacy of this diet for normal bone mineralization had not been sufficiently evaluated. Our aim was to evaluate and follow up bone mineral density (BMD) in children and adolescents with PKU within a 2-year time interval to assess the adequacy of a phenylalanine restricted diet for bone mineralization and to search for a possible relationship between BMD, dietary control and blood phenylalanine (phe) concentrations. MATERIAL AND METHODS: Thirty-two patients with classic PKU (3-19 years) were evaluated for their bone mineral status using dual energy X-ray absorptiometry (DEXA) both at the beginning (baseline) and the end (follow-up) of the study. RESULTS: Low BMD was detected in 31.25% at the start and in 6.25% of patients after 2 years follows-up. No relationship was found between BMD and the duration of diet compliance and phe level as well. CONCLUSIONS: In this study the low BMD detected in our patients was both at baseline and follow-up independent of diet restriction. A yearly DEXA would be highly beneficial for early detection and treatment, thus preventing osteoporosis and decreasing the risk of fractures. We also suggest the importance of searching for new emerging therapies such as enzyme substitution or gene therapy as low protein diet compliance was not enough to maintain normal bone mineral density. PMID- 22295035 TI - Frequency of Firmicutes and Bacteroidetes in gut microbiota in obese and normal weight Egyptian children and adults. AB - INTRODUCTION: Obesity and associated metabolic disorders are a worldwide epidemic. Recent evidence suggests that the microbial community in the human intestine may play an important role in the pathogenesis of obesity. The aim of this study was to assess the differences in the composition of the intestinal microbiota between obese and normal weight Egyptian children and adults. MATERIAL AND METHODS: The study included 79 subjects among whom 51 were obese (23 children and 28 adults), and 28 were subjects of normal weight (17 children and 11 adults). Faecal samples were collected from all subjects. Total DNA was extracted from collected stool samples and submitted to conventional PCR for detection of Firmicutes and Bacteroidetes. All the studied group was subjected to clinical and anthropometric evaluation. Laboratory assessment of fasting glucose, high sensitivity C-reactive protein (hsCRP) and lipid profile was performed. RESULTS: The proportions of the phyla Firmicutes and Bacteroidetes were statistically significantly increased in the obese group compared to the normal weight group (p < 0.001, p = 0.003 respectively). The study also found a statistically significant positive trend for higher hsCRP in subjects with positive Firmicutes (p = 0.004). However, no associations were found between positive Bacteroidetes and hsCRP. CONCLUSIONS: The results of this study indicate that obesity in Egyptian children and adults is associated with compositional changes in faecal microbiota with increase in the phyla Firmicutes and Bacteroidetes. This could be considered when developing strategies to control obesity and its associated diseases by modifying the gut microbiota. PMID- 22295036 TI - Accuracy of sonographic criteria in the decision for surgical treatment in infantile hypertrophic pyloric stenosis. AB - INTRODUCTION: Abdominal ultrasonography has replaced barium studies in establishing the diagnosis in difficult cases of infantile hypertrophic pyloric stenosis (IHPS). The aim of this retrospective study was to establish sonographic criteria of qualification for surgical treatment in children with IHPS. MATERIAL AND METHODS: Hundred and fifteen infants (98 boys and 17 girls) with suspected IHPS were treated between 2000 and 2009. Pyloric muscle thickness, pyloric diameter and pyloric length were measured in US scans in all patients. Results were compared with US results of 19 infants with negative diagnosis and 29 children of the reference group. RESULTS: Diagnosis of IHPS was confirmed by US examination in 96 children (83.5%). There were 86 boys in the group with male prevalence 8.6 : 1. The remaining 19 infants (16.5%) had a negative ultrasound. The mean PL (20.89 vs. 12.73), PMT (5.41 vs. 2.24), and PD (14.1 vs. 7.42) differed significantly between patients with and without pyloric stenosis (p < 0.0001). The mean PL (12.34), PMT (2.2), and PD (7.48) in the reference group did not differ statistically from values obtained in patients with negative IHPS diagnosis and were significantly lower than in children from the IHPS group (p < 0.0001). US imaging had a sensitivity of 98%, specificity of 100%, with a positive and negative predictive value of 100% and 90% respectively. CONCLUSIONS: This study confirmed that ultrasonography is the first choice of diagnostic method in an infant with suspected hypertrophic pyloric stenosis. In cases with an uncertain clinical diagnosis of IHPS the examination can be easily repeated. PMID- 22295037 TI - Hypermethylation of p16 and DAPK promoter gene regions in patients with non invasive urinary bladder cancer. AB - INTRODUCTION: The aim of the study was to examine the frequency of methylation status in promoter regions of p16 and DAPK genes in patients with non-invasive bladder cancer. MATERIAL AND METHODS: Forty-two patients (92.9% men, 73.8% smokers, 71.4% T1G1, 19.1% T1G2, 9.5% T1G3) and 36 healthy controls were studied. Isolation of genomic DNA from blood serum and methylation-specific PCR (MSP) were applied. Methylation status - methylated and unmethylated promoter regions of p16 and DAPK genes were analysed. RESULTS: Seventeen out of 42 patients (40.5%) had the methylated p16 gene, while methylation of the DAPK gene was seen in 27 of 42 cases (64.3%). In 12 patients (28.6%) both analysed genes were methylated. A statistically significant (p = 0.046) higher frequency of DAPK gene methylation (71.4%) was observed in patients with lower grade (G1) bladder cancer. CONCLUSIONS: Detection of the aberrant hypermethylation of DAPK and p16 genes in blood DNA from non-invasive bladder cancer patients might offer an effective means for earlier auxiliary diagnosis of the malignancy. PMID- 22295038 TI - The content of cadmium, cobalt and nickel in laryngeal carcinoma. AB - INTRODUCTION: The aim of the study was to determine the content of cadmium (Cd), cobalt (Co) and nickel (Ni) in the samples from laryngeal carcinoma in comparison with the level of these elements in the samples of healthy mucous membrane from the same larynx. MATERIAL AND METHODS: The study was conducted on 43 patients with laryngeal carcinoma. The levels of Cd, Co, and Ni in carcinoma and healthy control tissues was determined by inductively coupled plasma optical emission spectrometry (ICP - OES) using sequential spectrometer. RESULTS: No significant differences were found between the levels of the Cd, Co, and Ni in laryngeal carcinoma vs tissues without carcinoma. However, it was noted that the concentration of Cd in tumors of patients with metastases to cervical lymph nodes was significantly higher than in tumors without metastases. The content of Co was significantly higher in more advanced laryngeal tumors: in stage-T4 than in stage T3. It is of interest that the levels of Cd, Co and Ni were significantly higher in tumors in patients from rural than urban areas. CONCLUSIONS: The imbalance in the level of nickel, cadmium and cobalt in laryngeal cancer may be due to a changed cellular metabolism in the cancer process. However, the results of our study reveal the significant differences in the concentration of these metals between patients from urban and rural areas which suggests that this fact may be related to environmental or occupational factors and therefore it requires further study. PMID- 22295039 TI - Investigation of tRNA and ATPase 6/8 gene mutations in Iranian ataxia telangiectasia patients. AB - INTRODUCTION: Ataxia telangiectasia (AT) is a rare human neurodegenerative autosomal recessive multisystem disease. AT is the result of mutations in the AT mutated (ATM) gene. ATM protein is required for radiation-induced apoptosis and acts before mitochondrial collapse. The tRNA genes are considered one of the hot spots for mutations causing mitochondrial disorders. Due to the important role of ATM in apoptosis and its effect on the cell cycle it might be possible that it has a central role in mtDNA mutations. On the other hand, the tRNA(Lys/Leu) gene and also ATPase6 and ATPase8 genes are important for many mitochondrial diseases and many causative mutations have been reported from these genes. MATERIAL AND METHODS: In the present research, we performed mutation screening for these genes in 20 patients who were diagnosed with ataxia telangiectasia by a PCR sequencing method. RESULTS: The results showed a significant level of mtDNA variations in AT patients. Among 20 patients in this study, 12 patients (60%) were detected with point mutations, among which 8 mutations (40%) belonged to the MT-ATP6 gene. There was probably a second effect of mtDNA mutations in AT disease and mtDNA plays a main role in establishment of AT. CONCLUSIONS: MtDNA mutations might be responsible for the decline of mitochondrial function in AT patients. Mitochondrial investigation can help to understand the mechanism of damage in AT disease. PMID- 22295040 TI - Transapical aortic valve implantation - a rescue procedure for patients with aortic stenosis and "porcelain aorta". AB - Surgical aortic valve replacement (AVR) still remains the treatment of choice in symptomatic significant aortic stenosis (AS). Due to technical problems, extensive calcification of the ascending aorta ("porcelain aorta") is an additional risk factor for surgery and transapical aortic valve implantation (TAAVI) is likely to be the only rescue procedure for this group of patients. We describe the case of an 81-year-old woman with severe AS and "porcelain aorta", in whom the only available life-saving intervention was TAAVI. PMID- 22295041 TI - Emerging novel therapies for advanced prostate cancer. AB - This review examines the development and efficacy of novel treatment options for advanced prostate cancer and discusses novel therapies that are on the horizon. Since the introduction of docetaxel as the standard treatment for patients with metastatic castration-resistant prostate cancer (CRPC), a number of different agents have been tested but failed to demonstrate improvement in overall survival (OS). Recently, three novel compounds have demonstrated OS benefit and one other showed reduction in skeletal-related events (SREs). Sipuleucel-T, a novel vaccine, was approved by the US regulatory authorities in April 2010 for patients with early advanced prostate cancer. A new taxane, cabazitaxel, and abiraterone acetate, an androgen biosynthesis inhibitor, have shown an OS benefit in advanced CRPC after docetaxel, leading to drug approval. A new bone-targeting agent, denosumab, a receptor activator of nuclear factor kappaB ligand (RANKL) antagonist, showed a modest reduction in SREs in comparison to zoledronic acid in patients with bone metastases. Other promising novel agents are currently being tested in the clinical setting of advanced CRPC. These include, androgen receptor inhibitors (MDV3100), androgen biosynthesis inhibitors, angiogenesis inhibitors (thalidomide, lenalidomine, aflibercept, tasquinimod), a novel form of radiotherapy (radium-223), and immune-modulating compounds (PROSTVAC-VF). Improvements in progression-free survival and OS rates, observed with novel agents, in metastatic prostate cancer have led to a shift in treatment paradigm. The challenge will be to position the current established and expected novel treatments in the new landscape of metastatic prostate cancer and to determine at what point and time in the disease course they can best be administered. PMID- 22295043 TI - Natural orifice translumenal endoscopic radical prostatectomy. AB - The purpose of this publication is to document the evolution of a new surgical procedure for the treatment of carefully selected patients with organ confined localized prostate cancer. Natural orifice surgery represents a paradigm shift in the surgical approach to disease, although its adoption into clinical practice has been limited to date. This manuscript describes the development of natural orifice translumenal endoscopic surgical radical prostatectomy (NOTES RP). The laboratory, animal, preclinical and early clinical experiences are described and detailed. While the early experiences with this approach are promising and encouraging, more information is required. Despite the early successes with the procedure, long-term oncological and functional outcomes are essential and more work needs to be done to facilitate the teaching and ease of the NOTES RP. PMID- 22295042 TI - Best practice in the treatment of nonmuscle invasive bladder cancer. AB - Bladder carcinoma is the most common malignancy of the urinary tract. Approximately 75-85% of patients with bladder cancer present with a disease that is confined to the mucosa (stage Ta, carcinoma in situ) or submucosa (stage T1). These categories are grouped as nonmuscle invasive bladder cancer (NMIBC). Although the management of NMIBC tumours has significantly improved during the past few years, it remains difficult to predict the heterogeneous outcome of such tumours, especially if high-grade NMIBC is present. Transurethral resection is the initial treatment of choice for NMIBC. However, the high rates of recurrence and significant risk of progression in higher-grade tumours mandate additional therapy with intravesical agents. We discuss the role of various intravesical agents currently in use, including the immunomodulating agent bacillus Calmette Guerin (BCG) and chemotherapeutic agents. We also discuss the current guidelines and the role of these therapeutic agents in the context of higher-grade Ta and T1 tumours. Beyond the epidemiology, this article focuses on the risk factors, classification and diagnosis, the prediction of recurrence and progression in NMIBC, and the treatments advocated for this invasive disease. PMID- 22295044 TI - Congenital clavicular pseudarthrosis: comparison of two treatment methods. AB - BACKGROUND: Congenital pseudarthrosis of the clavicle is rare and popular surgical options include excision of the non-union, iliac crest bone grafting and stabilisation with either a fully threaded pin or stabilisation with a reconstruction plate. METHODS: Between 1995 and 2009, ten patients with congenital pseudarthrosis of the clavicle were retrospectively reviewed for outcome of two different forms of surgical management. Five patients had excision of the non-union, iliac crest bone grafting and stabilisation with a fully threaded pin (group A) and the other five patients had excision of the non-union, iliac crest bone grafting and stabilisation with a reconstruction plate (group B). One patient in the second group had bilateral pseudarthrosis. RESULTS: In group A, three patients achieved radiological union at a median of 6 months. Two patients failed to unite at the pseudarthrosis and one of them had further surgery with a reconstruction plate in order to achieve union. In group B, all five patients (six clavicles) achieved radiological union at a median of 3 months. All patients had painless full range of shoulder movement and were engaging in unrestricted activities. CONCLUSION: Excision of the pseudarthrosis, autogenous iliac bone grafting and stabilisation with plate achieves union quicker and with lower incidence of complications compared to excision of the pseudarthrosis, autogenous iliac bone grafting and stabilisation with fully threaded pins. PMID- 22295045 TI - Upper extremity surgery in younger children under ultrasound-guided supraclavicular brachial plexus block: a case series. AB - PURPOSE: Supraclavicular brachial plexus block is considered to be one of the most effective anesthetic procedures for upper extremity surgeries. Its major drawback is placement of the needle, with inaccurate placement, especially in children, being a risk factor for pneumothorax and vascular puncture and failure of the procedure. Ultrasound-guided needle placement may reduce the risk of complications and increase the accuracy of the block, particularly in pediatric patients. Little has been published on the efficacy and safety of ultrasound guided supraclavicular block in children based on practical experience, and there has been no published report on its usage in younger children (<6 years old). METHODS: Seventeen patients between the ages of 6 months and 6 years were randomly selected to test the efficacy of ultrasound-guided supraclavicular block in younger children. The ultrasound probe was used for proper placement of the needle. After confirmation of the needle location using a nerve locator, the anesthetic agent was injected. The procedure time, establishment time, duration of analgesia, any complications related to the procedure, and surgeon's satisfaction were recorded and assessed. RESULTS: The length of the procedure was 10.35 +/- 1.22 min, establishment time was 89.59 + 18 s, and the duration of the analgesia was between 6 and 16 h (mean 9.76 +/- 2.57 h). The recovery time was 24.4 + 6.5 min (range 15-37 min), and the duration of surgeries was 61.3 +/- 25.9 min (range 15-110 min). Not one procedure failed, and there was not one complication related to the procedure. The surgeon's satisfaction during surgery was good or excellent. CONCLUSIONS: The results of this study demonstrate the efficacy and safety of the ultrasound-guided supraclavicular brachial plexus block for orthopedic upper extremity surgeries in patients less than 6 years of age. PMID- 22295046 TI - Tibial fractures after tibial tubercle osteotomies for patellar instability: a comparison of three osteotomy configurations. AB - PURPOSE: Tibial tubercle osteotomies (TTOs) are a seemingly straightforward technique; however problems with bony union, implant failure, wound infections, and fractures have been reported in the literature. METHODS: A database search identified all patients who had a TTO performed for patellofemoral instability between 1 March 2000 and 30 July 2008 by a single surgeon. The TTO technique was modified twice during the study period (December 2003 and June 2007, respectively), thereby creating three similar patient cohorts. RESULTS: TTOs were performed in 101 knees (90 patients), in which 34 knees (29 patients) received the blunt technique (TTO-B), 32 knees (30 patients) the sloped technique (TTO-S), and 35 knees (31 patients) the greenstick technique (TTO-G). Mean age of the patients (75 females, 15 males) was 16.0 years (range 12.2-20.2 years). Overall, six patients had complications, namely, six tibia fractures and no nonunions, for an overall complication rate of 5.9%. In the TTO-B group, four patients had four tibia fractures for an overall bony complication rate of 11.8%. In the TTO-S group, two patients had two delayed unions which developed into tibia fractures for an overall bony complication rate of 6.2%. There were no complications (0%) in the TTO-G group. No correlation was identified between TTO screw size and complications. The caudal aspect of the osteotomy was the location of the tibia fracture in five knees and the caudal screw in 1 knee, at a mean of 11 weeks postoperatively. All fractures were treated only with splint or cast immobilization and protected weight-bearing. CONCLUSION: The overall bony complication rate was 5.9% for the TTOs in this study. Utilizing the TTO-G technique with rigid two-screw, bicortical fixation the complication rate could be lowered to 0%. Avoidance of periosteal stripping, and secondary cortical devascularization at the caudal aspect of the TTO appears to optimize bony consolidation, thereby minimizing fractures. CLINICAL RELEVANCE: Bony complications are an infrequent problem after TTO. Greensticking the distal end of the TTO can minimize postoperative tibia fractures. Running and sports should not be permitted until complete cortical healing is documented on the lateral radiograph. PMID- 22295047 TI - Surgical management of post-SCIWORA spinal deformities in children. AB - BACKGROUND: Patients with spinal cord injury without radiographic abnormality (SCIWORA) are prone to develop spinal deformities. The purpose of this study is to report on the clinical and radiological features of post-SCIWORA spinal deformities. METHODS: Four patients with SCIWORA and spinal deformities requiring surgery were analyzed clinically and radiographically. RESULTS: All four SCIWORA patients developed progressive neuromuscular scoliosis. There were 2 males and 2 females. The mean age at spinal cord injury was 3.9 years (range 6 months to 7 years). Spinal deformity was first noticed at a mean of 17 months after their initial injury (range 9 months to 2 years), and surgical intervention was performed at a mean of 6.5 years following their injury (range 4-11 years). The mean preoperative curve was 54 degrees (range 50-62 degrees ). The mean postoperative curve was 9.5 degrees (range 5-16 degrees ). The level of injury was T5 in two patients, and T10 and L2 in one patient each. All but the lumbar level injury patient had complete paraplegia. One patient with complete injury (T10) and another with incomplete injury (L2) improved neurologically and were able to walk with the aid of orthoses and crutches. Pelvic obliquity improved in all patients following spinal reconstruction surgery, and none of the patients required additional surgery for spinal deformity. The mean postoperative follow up was 51.75 months (range 24-93 months). CONCLUSIONS: Long scoliotic curves extending to the pelvis should be expected in SCIWORA. Early intervention may prevent severe deformities. Modern instrumentation techniques employing pedicle screws provided satisfactory correction, improved hip subluxation, and did not adversely affect the ambulatory ability or functional level of the patients in this series. PMID- 22295048 TI - A new pelvic rod system for the surgical correction and fixation of pelvic obliquity in pediatric neuromuscular scoliosis. AB - PURPOSE: To describe surgical outcomes using the new device in pediatric neuromuscular scoliosis. METHODS: All patients with neuromuscular disorders requiring surgery with pelvic fixation for the correction of scoliosis in the period 2002-2009 were operated by the new pelvic rod fixation device. Coronal and sagittal alignment before and after surgery until the latest follow-up were evaluated by standard X-rays. Intraoperative and postoperative complications were recorded. RESULTS: All 18 study patients (mean age at surgery 15 years, range 10 27) achieved solid fusion at a mean follow-up of 41 months. The coronal Cobb angle improved from 82 degrees +/- 31 degrees (range 36-168) to 33 degrees +/- 25 degrees at the last follow-up (range 9-95 months) (P < 0.0001). Pelvic obliquity improved from 19 degrees +/- 6 degrees (range 10-30) to 5 degrees +/ 5 degrees (range 0-14) (P < 0.0001). Early complications included pneumonia, urinary tract infection, disseminated intravascular coagulation (DIC), and hypovolemic shock. Three patients required debriding and received prolonged antimicrobial therapy for deep wound infection (none required implant removal). At the latest follow-up, no patient complained of lumbar pain or worsening of ambulatory status or level of activity. CONCLUSION: Surgery employing the new pelvic rod fixation device allowed solid fusion and fixation with significant correction of multiplanar deformity, but the complication rate was high. PMID- 22295049 TI - Adolescent disc dysplasia and back pain. AB - PURPOSE: Adolescent disc dysplasia can be a cause of significant back pain and functional impairment in patients. We present a case series of patients inflicted with adolescent disc dysplasia (ADD). METHODS: A retrospective search was performed identifying patients presenting with ADD. Radiographic studies and advanced imaging were described. We documented presenting symptoms and clinical course. RESULTS: Six patients were identified. All patients presented with mechanical back pain, which worsened with flexion and extension. Magnetic resonance imaging was most accurate imaging modality. CONCLUSION: Among our patient cohort, treatment for adolescent disc dysplasia consisted of a combination of physical therapy and bracing. Neither approach proved to be very effective, with only one patient asymptomatic at follow-up. PMID- 22295050 TI - Lumbopelvic fusion with a new fixation technique in lumbosacral agenesis: three cases. AB - PURPOSE: Patients with lumbosacral agenesis characteristically sit on their iliac wings with their torsos bent forward, which yields an increase in intra-abdominal pressure and, subsequently, negative effects on their diaphragm. The sacrum is not available as an anchor point for instrumentation. Dunn-McCarthy rods or Galveston fixations cannot be performed due to these limited anatomic properties. On the other hand, the absence of necessary bone mass for fusion anteriorly limits the fusion interventions to the posterior. Therefore, a secure and rigid fixation is essential to preclude the need for an external support. There are limited publications discussing different techniques due to the relatively rare incidence of the disease. We report the clinical and radiological results of a new technique applied to three patients in which previously recommended methods are modified. METHODS: Two 6-year-old female patients and one 5-year-old male patient with lumbosacral agenesis underwent posterior lumbopelvic instrumentation and fusion. Together with standard pedicle screw spinal instrumentation, pelvic fixation is obtained with a combination of supero-inferior directed rod and/or screw to overcome deforming forces created at the flexion-extension pivot points of the lumbopelvic junction. Autogenic anterior tibial cortical structural graft is used for laminopelvic bridging, and demineralized bone matrix is used for the augmentation of osteoinduction. A single leg hip spica is applied for 4 months to protect the fixation. RESULTS: Total correction yielded an aligned spine with a posture that allows for sitting on the ischial spines for all three patients. Solid fusion was observed to maintain this correction at the final follow-up. CONCLUSION: The use of new-generation pediatric spinal instrumentation systems with a new technique without knee disarticulation provides a safe and effective fixation and fusion in lumbosacral agenesis. PMID- 22295051 TI - Use of a "kickstand" modification for external fixation of lower extremity fractures in children. AB - PURPOSE: To evaluate and describe the kickstand modification and its use in children with lower extremity fractures. METHODS: Retrospective review identified eight children in whom the kickstand technique was used during treatment of their lower extremity fractures. The seven boys and one girl had a mean age of 11.8 years. All fractures were caused by high-energy trauma. Five of the eight tibial fractures were open fractures (one type 1, one type 2, and three type 3B), and five of the eight patients had multiple extremity fractures. RESULTS: Additional procedures were required in six of the eight children, four of whom had multiple lower extremity fractures. No additional pressure-relieving modalities were used in any patient. The kickstand did not affect the fracture reduction, prevent patient mobilization, or require operative adjustment in any patient, and none had any skin pressure-related complications on the heel of the affected extremity. CONCLUSION: In pediatric patients with lower extremity trauma, the addition of a kickstand to the external fixator provides a simple, inexpensive, lightweight, adjustable, and adaptable method for encouraging elevation of the injured extremity, which facilitates edema control; it also allows easy neurovascular monitoring and wound care. PMID- 22295052 TI - Can orthopaedic clinicians learn to read skeletal bone age? An inter- and intra observer study between specialties. AB - OBJECTIVE: Determination of skeletal age is essential for predicting eventual leg length discrepancies and predicting the accurate timing for surgical intervention in order to correct any discrepancy. To our knowledge, there has not been an interdisciplinary comparison of the degree of agreement in determining skeletal bone age. MATERIALS AND METHODS: We evaluated 30 left hand/wrist radiographs (children aged 16 months to 10 years 6 months) on two separate occasions between musculoskeletal paediatric radiologists, paediatric orthopaedic surgeons and a senior radiographer after appropriate training. RESULTS: All clinicians were able to reliably age patients with good intra- and interobserver agreement. CONCLUSION: We suggest that following tuition, orthopaedic surgeons are able to reliably age patients from X-rays. PMID- 22295053 TI - Activator-induced dynamic disorder and molecular memory in human two-pore domain hTREK1 K channel. AB - Ion channels are fundamental molecules in the nervous system that catalyze the flux of ions across the cell membrane. Ion channel flux activity is comparable to the catalytic activity of enzyme molecules. Saturating concentrations of substrate induce "dynamic disorder" in the kinetic rate processes of single enzyme molecules and consequently, develop correlative "memory" of the previous history of activities. Similarly, binding of ions as substrate alone or in presence of agonists affects the catalytic turnover of single-ion channels. Here, we investigated the possible existence of dynamic disorder and molecular memory in the single human-TREK1-channel due to binding of substrate/agonist using the excised inside-out patch-clamp technique. Our results suggest that the single hTREK1-channel behaves as a typical Michaelis-Menten enzyme molecule with a high affinity binding site for K(+) ion as substrate. But, in contrast to enzyme, dynamic disorder in single-hTREK1-channel was not induced by substrate K(+) binding, but required allosteric modification of the channel molecule by the agonist, trichloroethanol. In addition, interaction of trichloroethanol with hTREK1 induced strong correlation in the waiting time and flux intensity, exemplified by distinct mode-switching between high and low flux activities. This suggested the induction of molecular memory in the channel molecule by the agonist, which persisted for several decades in time. Our mathematical modeling studies identified the kinetic rate processes associated with dynamic disorder. It further revealed the presence of multiple populations of distinct conformations that contributed to the "heterogeneity" and consequently, to the molecular memory phenomenon that we observed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12154-010-0053-3) contains supplementary material, which is available to authorized users. PMID- 22295056 TI - Genome wide association identifies PPFIA1 as a candidate gene for acute lung injury risk following major trauma. AB - Acute Lung Injury (ALI) is a syndrome with high associated mortality characterized by severe hypoxemia and pulmonary infiltrates in patients with critical illness. We conducted the first investigation to use the genome wide association (GWA) approach to identify putative risk variants for ALI. Genome wide genotyping was performed using the Illumina Human Quad 610 BeadChip. We performed a two-stage GWA study followed by a third stage of functional characterization. In the discovery phase (Phase 1), we compared 600 European American trauma-associated ALI cases with 2266 European American population-based controls. We carried forward the top 1% of single nucleotide polymorphisms (SNPs) at p<0.01 to a replication phase (Phase 2) comprised of a nested case-control design sample of 212 trauma-associated ALI cases and 283 at-risk trauma non-ALI controls from ongoing cohort studies. SNPs that replicated at the 0.05 level in Phase 2 were subject to functional validation (Phase 3) using expression quantitative trait loci (eQTL) analyses in stimulated B-lymphoblastoid cell lines (B-LCL) in family trios. 159 SNPs from the discovery phase replicated in Phase 2, including loci with prior evidence for a role in ALI pathogenesis. Functional evaluation of these replicated SNPs revealed rs471931 on 11q13.3 to exert a cis regulatory effect on mRNA expression in the PPFIA1 gene (p = 0.0021). PPFIA1 encodes liprin alpha, a protein involved in cell adhesion, integrin expression, and cell-matrix interactions. This study supports the feasibility of future multi center GWA investigations of ALI risk, and identifies PPFIA1 as a potential functional candidate ALI risk gene for future research. PMID- 22295057 TI - Functional promoter -31G>C variant in survivin gene is associated with risk and progression of renal cell cancer in a Chinese population. AB - BACKGROUND: Survivin is an inhibitor of apoptosis protein and is involved in the occurrence and progression of human malignancies. Recently, a functional polymorphism (-31G>C, rs9904341) in the promoter of survivin has been shown to influence its expression and confer susceptibility to different types of cancer. The present study was aimed to investigate whether the polymorphism also influences susceptibility and progression of renal cell cancer (RCC) in a Chinese population. METHODS: We genotyped this polymorphism using the TaqMan assay in a case-control study comprised of 710 RCC patients and 760 controls. The logistic regression was used to assess the genetic association with occurrence and progression of RCC. RESULTS: Compared with the genotypes containing G allele (GG and GC), we found a statistically significant increased occurrence of RCC associated with the CC genotype [P = 0.006, adjusted odds ratio (OR) = 1.38, 95% confidence interval (CI) = 1.08-1.76]. The polymorphism was associated with risk of developing advanced stage (OR = 2.02, 95%CI = 1.34-3.07) and moderately differentiated (OR = 1.75; 95%CI = 1.20-2.54) RCC. Furthermore, the patients carrying the CC genotype had a significantly greater prevalence of high clinical stage disease (P(trend) = 0.003). Similar results were also observed when we restricted the analysis to clear cell RCC, a major histological type of RCC. CONCLUSIONS: Our results suggest that the functional -31G>C polymorphism in the promoter of survivin may influence the susceptibility and progression of RCC in the Chinese population. Large population-based prospective studies are required to validate our findings. PMID- 22295058 TI - Genetic profiling using genome-wide significant coronary artery disease risk variants does not improve the prediction of subclinical atherosclerosis: the Cardiovascular Risk in Young Finns Study, the Bogalusa Heart Study and the Health 2000 Survey--a meta-analysis of three independent studies. AB - BACKGROUND: Genome-wide association studies (GWASs) have identified a large number of variants (SNPs) associating with an increased risk of coronary artery disease (CAD). Recently, the CARDIoGRAM consortium published a GWAS based on the largest study population so far. They successfully replicated twelve already known associations and discovered thirteen new SNPs associating with CAD. We examined whether the genetic profiling of these variants improves prediction of subclinical atherosclerosis--i.e., carotid intima-media thickness (CIMT) and carotid artery elasticity (CAE)--beyond classical risk factors. SUBJECTS AND METHODS: We genotyped 24 variants found in a population of European ancestry and measured CIMT and CAE in 2001 and 2007 from 2,081, and 2,015 subjects (aged 30-45 years in 2007) respectively, participating in the Cardiovascular Risk in Young Finns Study (YFS). The Bogalusa Heart Study (BHS; n = 1179) was used as a replication cohort (mean age of 37.5). For additional replication, a sub-sample of 5 SNPs was genotyped for 1,291 individuals aged 46-76 years participating in the Health 2000 population survey. We tested the impact of genetic risk score (GRS(24SNP/CAD)) calculated as a weighted (by allelic odds ratios for CAD) sum of CAD risk alleles from the studied 24 variants on CIMT, CAE, the incidence of carotid atherosclerosis and the progression of CIMT and CAE during a 6-year follow-up. RESULTS: CIMT or CAE did not significantly associate with GRS(24SNP/CAD) before or after adjusting for classical CAD risk factors (p>0.05 for all) in YFS or in the BHS. CIMT and CAE associated with only one SNP each in the YFS. The findings were not replicated in the replication cohorts. In the meta analysis CIMT or CAE did not associate with any of the SNPs. CONCLUSION: Genetic profiling, by using known CAD risk variants, should not improve risk stratification for subclinical atherosclerosis beyond conventional risk factors among healthy young adults. PMID- 22295059 TI - Life events, coping, and posttraumatic stress symptoms among Chinese adolescents exposed to 2008 Wenchuan Earthquake, China. AB - PURPOSE: To examine the relationship between negative life events, coping styles, and symptoms of post-traumatic stress disorder (PTSD) among adolescent survivors exposed to 2008 Wenchuan Earthquake, China. METHODS: A survey was conducted in a sample of 2250 adolescent students from two schools in Dujiangyan District, a seriously damaged area, 20 kilometers away from the epicenter, 6 months after the earthquake. Participants completed a self-administered questionnaire including demographics, negative life events, coping styles, and PTSD symptoms. RESULTS: Academic pressure was the strongest predictor of adolescents' PTSD symptoms among all negative life events. Main effects of negative life events, positive coping and negative coping on PTSD symptoms were significant in both younger adolescents and older adolescents, while the moderator effects of two coping styles were found significant only within older adolescents. CONCLUSIONS: Coping may play a role to moderate the relationship between post-earthquake negative life events and PTSD symptom, but the function seems to depend on the age of participants. Psychosocial coping skills training may be important in the prevention and intervention of mental health problems in adolescent survivors of traumatic earthquake. PMID- 22295060 TI - Shifting from population-wide to personalized cancer prognosis with microarrays. AB - The era of personalized medicine for cancer therapeutics has taken an important step forward in making accurate prognoses for individual patients with the adoption of high-throughput microarray technology. However, microarray technology in cancer diagnosis or prognosis has been primarily used for the statistical evaluation of patient populations, and thus excludes inter-individual variability and patient-specific predictions. Here we propose a metric called clinical confidence that serves as a measure of prognostic reliability to facilitate the shift from population-wide to personalized cancer prognosis using microarray based predictive models. The performance of sample-based models predicted with different clinical confidences was evaluated and compared systematically using three large clinical datasets studying the following cancers: breast cancer, multiple myeloma, and neuroblastoma. Survival curves for patients, with different confidences, were also delineated. The results show that the clinical confidence metric separates patients with different prediction accuracies and survival times. Samples with high clinical confidence were likely to have accurate prognoses from predictive models. Moreover, patients with high clinical confidence would be expected to live for a notably longer or shorter time if their prognosis was good or grim based on the models, respectively. We conclude that clinical confidence could serve as a beneficial metric for personalized cancer prognosis prediction utilizing microarrays. Ascribing a confidence level to prognosis with the clinical confidence metric provides the clinician an objective, personalized basis for decisions, such as choosing the severity of the treatment. PMID- 22295061 TI - Fishing the molecular bases of Treacher Collins syndrome. AB - Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, and mutations in the TCOF1 gene are responsible for over 90% of TCS cases. The knowledge about the molecular mechanisms responsible for this syndrome is relatively scant, probably due to the difficulty of reproducing the pathology in experimental animals. Zebrafish is an emerging model for human disease studies, and we therefore assessed it as a model for studying TCS. We identified in silico the putative zebrafish TCOF1 ortholog and cloned the corresponding cDNA. The derived polypeptide shares the main structural domains found in mammals and amphibians. Tcof1 expression is restricted to the anterior-most regions of zebrafish developing embryos, similar to what happens in mouse embryos. Tcof1 loss-of-function resulted in fish showing phenotypes similar to those observed in TCS patients, and enabled a further characterization of the mechanisms underlying craniofacial malformation. Besides, we initiated the identification of potential molecular targets of treacle in zebrafish. We found that Tcof1 loss-of-function led to a decrease in the expression of cellular proliferation and craniofacial development. Together, results presented here strongly suggest that it is possible to achieve fish with TCS-like phenotype by knocking down the expression of the TCOF1 ortholog in zebrafish. This experimental condition may facilitate the study of the disease etiology during embryonic development. PMID- 22295062 TI - The time course of the influence of valence and arousal on the implicit processing of affective pictures. AB - In the current study, we investigated the time course of the implicit processing of affective pictures with an orthogonal design of valence (negative vs. positive) by arousal (low vs. high). Previous studies with explicit tasks suggested that valence mainly modulates early event-related potential (ERP) components, whereas arousal mainly modulates late components. However, in this study with an implicit task, we observed significant interactions between valence and arousal at both early and late stages over both parietal and frontal sites, which were reflected by three different ERP components: P2a (100-200 ms), N2 (200 300 ms), and P3 (300-400 ms). Furthermore, there was also a significant main effect of arousal on P2b (200-300 ms) over parieto-occipital sites. Our results suggest that valence and arousal effects on implicit affective processing are more complicated than previous ERP studies with explicit tasks have revealed. PMID- 22295063 TI - MicroRNA signatures in tumor tissue related to angiogenesis in non-small cell lung cancer. AB - BACKGROUND: Angiogenesis is regarded as a hallmark in cancer development, and anti-angiogenic treatment is presently used in non-small cell lung cancer (NSCLC) patients. MicroRNAs (miRs) are small non-coding, endogenous, single stranded RNAs that regulate gene expression. In this study we aimed to identify significantly altered miRs related to angiogenesis in NSCLC. METHODS: From a large cohort of 335 NSCLC patients, paraffin-embedded samples from 10 patients with a short disease specific survival (DSS), 10 with a long DSS and 10 normal controls were analyzed. The miRs were quantified by microarray hybridization and selected miRs were validated by real-time qPCR. The impacts of different pathways, including angiogenesis, were evaluated by Gene Set Enrichment Analysis (GSEA) derived from Protein ANalysis THrough Evolutionary Relationship (PANTHER). One of the most interesting candidate markers, miR-155, was validated by in situ hybridization (ISH) in the total cohort (n = 335) and correlation analyses with several well known angiogenic markers were done. RESULTS: 128 miRs were significantly up- or down-regulated; normal versus long DSS (n = 68) and/or normal versus short DSS (n = 63) and/or long versus short DSS (n = 37). The pathway analysis indicates angiogenesis-related miRs to be involved in NSCLC. There were strong significant correlations between the array hybridization and qPCR validation data. The significantly altered angiogenesis-related miRs of high interest were miR-21, miR 106a, miR-126, miR-155, miR-182, miR-210 and miR-424. miR-155 correlated significantly with fibroblast growth factor 2 (FGF2) in the total cohort (r = 0.17, P = 0.002), though most prominent in the subgroup with nodal metastasis (r = 0.34, P<0.001). CONCLUSIONS: Several angiogenesis-related miRs are significantly altered in NSCLC. Further studies to understand their biological functions and explore their clinical relevance are warranted. PMID- 22295064 TI - Y chromosome lineages in men of west African descent. AB - The early African experience in the Americas is marked by the transatlantic slave trade from ~1619 to 1850 and the rise of the plantation system. The origins of enslaved Africans were largely dependent on European preferences as well as the availability of potential laborers within Africa. Rice production was a key industry of many colonial South Carolina low country plantations. Accordingly, rice plantations owners within South Carolina often requested enslaved Africans from the so-called "Grain Coast" of western Africa (Senegal to Sierra Leone). Studies on the African origins of the enslaved within other regions of the Americas have been limited. To address the issue of origins of people of African descent within the Americas and understand more about the genetic heterogeneity present within Africa and the African Diaspora, we typed Y chromosome specific markers in 1,319 men consisting of 508 west and central Africans (from 12 populations), 188 Caribbeans (from 2 islands), 532 African Americans (AAs from Washington, DC and Columbia, SC), and 91 European Americans. Principal component and admixture analyses provide support for significant Grain Coast ancestry among African American men in South Carolina. AA men from DC and the Caribbean showed a closer affinity to populations from the Bight of Biafra. Furthermore, 30-40% of the paternal lineages in African descent populations in the Americas are of European ancestry. Diverse west African ancestries and sex-biased gene flow from EAs has contributed greatly to the genetic heterogeneity of African populations throughout the Americas and has significant implications for gene mapping efforts in these populations. PMID- 22295065 TI - TLR2/MyD88/NF-kappaB pathway, reactive oxygen species, potassium efflux activates NLRP3/ASC inflammasome during respiratory syncytial virus infection. AB - Human respiratory syncytial virus (RSV) constitute highly pathogenic virus that cause severe respiratory diseases in newborn, children, elderly and immuno compromised individuals. Airway inflammation is a critical regulator of disease outcome in RSV infected hosts. Although "controlled" inflammation is required for virus clearance, aberrant and exaggerated inflammation during RSV infection results in development of inflammatory diseases like pneumonia and bronchiolitis. Interleukin-1beta (IL-1beta) plays an important role in inflammation by orchestrating the pro-inflammatory response. IL-1beta is synthesized as an immature pro-IL-1beta form. It is cleaved by activated caspase-1 to yield mature IL-1beta that is secreted extracellularly. Activation of caspase-1 is mediated by a multi-protein complex known as the inflammasome. Although RSV infection results in IL-1beta release, the mechanism is unknown. Here in, we have characterized the mechanism of IL-1beta secretion following RSV infection. Our study revealed that NLRP3/ASC inflammasome activation is crucial for IL-1beta production during RSV infection. Further studies illustrated that prior to inflammasome formation; the "first signal" constitutes activation of toll-like receptor-2 (TLR2)/MyD88/NF kappaB pathway. TLR2/MyD88/NF-kappaB signaling is required for pro-IL-1beta and NLRP3 gene expression during RSV infection. Following expression of these genes, two "second signals" are essential for triggering inflammasome activation. Intracellular reactive oxygen species (ROS) and potassium (K(+)) efflux due to stimulation of ATP-sensitive ion channel promote inflammasome activation following RSV infection. Thus, our studies have underscored the requirement of TLR2/MyD88/NF-kappaB pathway (first signal) and ROS/potassium efflux (second signal) for NLRP3/ASC inflammasome formation, leading to caspase-1 activation and subsequent IL-1beta release during RSV infection. PMID- 22295066 TI - Facemasks, hand hygiene, and influenza among young adults: a randomized intervention trial. AB - Limited vaccine availability and the potential for resistance to antiviral medications have led to calls for establishing the efficacy of non-pharmaceutical measures for mitigating pandemic influenza. Our objective was to examine if the use of face masks and hand hygiene reduced rates of influenza-like illness (ILI) and laboratory-confirmed influenza in the natural setting. A cluster-randomized intervention trial was designed involving 1,178 young adults living in 37 residence houses in 5 university residence halls during the 2007-2008 influenza season. Participants were assigned to face mask and hand hygiene, face mask only, or control group during the study. Discrete-time survival models using generalized estimating equations to estimate intervention effects on ILI and confirmed influenza A/B infection over a 6-week study period were examined. A significant reduction in the rate of ILI was observed in weeks 3 through 6 of the study, with a maximum reduction of 75% during the final study week (rate ratio [RR] = 0.25, [95% CI, 0.07 to 0.87]). Both intervention groups compared to the control showed cumulative reductions in rates of influenza over the study period, although results did not reach statistical significance. Generalizability limited to similar settings and age groups. Face masks and hand hygiene combined may reduce the rate of ILI and confirmed influenza in community settings. These non pharmaceutical measures should be recommended in crowded settings at the start of an influenza pandemic. TRIAL REGISTRATION: [corrected] Clinicaltrials.gov NCT00490633. PMID- 22295067 TI - Selective non-steroidal glucocorticoid receptor agonists attenuate inflammation but do not impair intestinal epithelial cell restitution in vitro. AB - INTRODUCTION: Despite the excellent anti-inflammatory and immunosuppressive action of glucocorticoids (GCs), their use for the treatment of inflammatory bowel disease (IBD) still carries significant risks in terms of frequently occurring severe side effects, such as the impairment of intestinal tissue repair. The recently-introduced selective glucocorticoid receptor (GR) agonists (SEGRAs) offer anti-inflammatory action comparable to that of common GCs, but with a reduced side effect profile. METHODS: The in vitro effects of the non steroidal SEGRAs Compound A (CpdA) and ZK216348, were investigated in intestinal epithelial cells and compared to those of Dexamethasone (Dex). GR translocation was shown by immunfluorescence and Western blot analysis. Trans-repressive effects were studied by means of NF-kappaB/p65 activity and IL-8 levels, trans activation potency by reporter gene assay. Flow cytometry was used to assess apoptosis of cells exposed to SEGRAs. The effects on IEC-6 and HaCaT cell restitution were determined using an in vitro wound healing model, cell proliferation by BrdU assay. In addition, influences on the TGF-beta- or EGF/ERK1/2/MAPK-pathway were evaluated by reporter gene assay, Western blot and qPCR analysis. RESULTS: Dex, CpdA and ZK216348 were found to be functional GR agonists. In terms of trans-repression, CpdA and ZK216348 effectively inhibited NF-kappaB activity and IL-8 secretion, but showed less trans-activation potency. Furthermore, unlike SEGRAs, Dex caused a dose-dependent inhibition of cell restitution with no effect on cell proliferation. These differences in epithelial restitution were TGF-beta-independent but Dex inhibited the EGF/ERK1/2/MAPK pathway important for intestinal epithelial wound healing by induction of MKP-1 and Annexin-1 which was not affected by CpdA or ZK216348. CONCLUSION: Collectively, our results indicate that, while their anti-inflammatory activity is comparable to Dex, SEGRAs show fewer side effects with respect to wound healing. The fact that SEGRAs did not have a similar effect on cell restitution might be due to a different modulation of EGF/ERK1/2 MAPK signalling. PMID- 22295068 TI - Effects of STN and GPi deep brain stimulation on impulse control disorders and dopamine dysregulation syndrome. AB - OBJECTIVE: Impulse control disorders (ICDs) and dopamine dysregulation syndrome (DDS) are important behavioral problems that affect a subpopulation of patients with Parkinson's disease (PD) and typically result in markedly diminished quality of life for patients and their caregivers. We aimed to investigate the effects of subthalamic nucleus (STN) and internal globus pallidus (GPi) deep brain stimulation (DBS) on ICD/DDS frequency and dopaminergic medication usage. METHODS: A retrospective chart review was performed on 159 individuals who underwent unilateral or bilateral PD DBS surgery in either STN or GPi. According to published criteria, pre- and post-operative records were reviewed to categorize patients both pre- and post-operatively as having ICD, DDS, both ICD and DDS, or neither ICD nor DDS. Group differences in patient demographics, clinical presentations, levodopa equivalent dose (LED), and change in diagnosis following unilateral/bilateral by brain target (STN or GPi DBS placement) were examined. RESULTS: 28 patients met diagnostic criteria for ICD or DDS pre- or post-operatively. ICD or DDS classification did not differ by GPi or STN target stimulation. There was no change in DDS diagnosis after unilateral or bilateral stimulation. For ICD, diagnosis resolved in 2 of 7 individuals after unilateral or bilateral DBS. Post-operative development of these syndromes was significant; 17 patients developed ICD diagnoses post-operatively with 2 patients with pre operative ICD developing DDS post-operatively. CONCLUSIONS: Unilateral or bilateral DBS did not significantly treat DDS or ICD in our sample, even though a few cases of ICD resolved post-operatively. Rather, our study provides preliminary evidence that DDS and ICD diagnoses may emerge following DBS surgery. PMID- 22295069 TI - Transient ureteral obstruction prevents against kidney ischemia/reperfusion injury via hypoxia-inducible factor (HIF)-2alpha activation. AB - Although the protective effect of transient ureteral obstruction (UO) prior to ischemia on subsequent renal ischemia/reperfusion (I/R) injury has been documented, the underlying molecular mechanism remains to be understood. We showed in the current study that 24 h of UO led to renal tubular hypoxia in the ipsilateral kidney in mice, with the accumulation of hypoxia-inducible factor (HIF)-2alpha, which lasted for a week after the release of UO. To address the functions of HIF-2alpha in UO-mediated protection of renal IRI, we utilized the Mx-Cre/loxP recombination system to knock out target genes. Inactivation of HIF 2alpha, but not HIF-1alpha blunted the renal protective effects of UO, as demonstrated by much higher serum creatinine level and severer histological damage. UO failed to prevent postischemic neutrophil infiltration and apoptosis induction in HIF-2alpha knockout mice, which also diminished the postobstructive up-regulation of the protective molecule, heat shock protein (HSP)-27. The renal protective effects of UO were associated with the improvement of the postischemic recovery of intra-renal microvascular blood flow, which was also dependent on the activation of HIF-2alpha. Our results demonstrated that UO protected the kidney via activation of HIF-2alpha, which reduced tubular damages via preservation of adequate renal microvascular perfusion after ischemia. Thus, preconditional HIF 2alpha activation might serve as a novel therapeutic strategy for the treatment of ischemic acute renal failure. PMID- 22295070 TI - Clinical, epidemiologic, histopathologic and molecular features of an unexplained dermopathy. AB - BACKGROUND: Morgellons is a poorly characterized constellation of symptoms, with the primary manifestations involving the skin. We conducted an investigation of this unexplained dermopathy to characterize the clinical and epidemiologic features and explore potential etiologies. METHODS: A descriptive study was conducted among persons at least 13 years of age and enrolled in Kaiser Permanente Northern California (KPNC) during 2006-2008. A case was defined as the self-reported emergence of fibers or materials from the skin accompanied by skin lesions and/or disturbing skin sensations. We collected detailed epidemiologic data, performed clinical evaluations and geospatial analyses and analyzed materials collected from participants' skin. RESULTS: We identified 115 case patients. The prevalence was 3.65 (95% CI = 2.98, 4.40) cases per 100,000 enrollees. There was no clustering of cases within the 13-county KPNC catchment area (p = .113). Case-patients had a median age of 52 years (range: 17-93) and were primarily female (77%) and Caucasian (77%). Multi-system complaints were common; 70% reported chronic fatigue and 54% rated their overall health as fair or poor with mean Physical Component Scores and Mental Component Scores of 36.63 (SD = 12.9) and 35.45 (SD = 12.89), respectively. Cognitive deficits were detected in 59% of case-patients and 63% had evidence of clinically significant somatic complaints; 50% had drugs detected in hair samples and 78% reported exposure to solvents. Solar elastosis was the most common histopathologic abnormality (51% of biopsies); skin lesions were most consistent with arthropod bites or chronic excoriations. No parasites or mycobacteria were detected. Most materials collected from participants' skin were composed of cellulose, likely of cotton origin. CONCLUSIONS: This unexplained dermopathy was rare among this population of Northern California residents, but associated with significantly reduced health-related quality of life. No common underlying medical condition or infectious source was identified, similar to more commonly recognized conditions such as delusional infestation. PMID- 22295071 TI - The ankyrin repeat domain of the TRPA protein painless is important for thermal nociception but not mechanical nociception. AB - The Drosophila TRPA channel Painless is required for the function of polymodal nociceptors which detect noxious heat and noxious mechanical stimuli. These functions of Painless are reminiscent of mammalian TRPA channels that have also been implicated in thermal and mechanical nociception. A popular hypothesis to explain the mechanosensory functions of certain TRP channels proposes that a string of ankyrin repeats at the amino termini of these channels acts as an intracellular spring that senses force. Here, we describe the identification of two previously unknown Painless protein isoforms which have fewer ankyrin repeats than the canonical Painless protein. We show that one of these Painless isoforms, that essentially lacks ankyrin repeats, is sufficient to rescue mechanical nociception phenotypes of painless mutant animals but does not rescue thermal nociception phenotypes. In contrast, canonical Painless, which contains Ankyrin repeats, is sufficient to largely rescue thermal nociception but is not capable of rescuing mechanical nociception. Thus, we propose that in the case of Painless, ankryin repeats are important for thermal nociception but not for mechanical nociception. PMID- 22295072 TI - Associations between organochlorine pesticides and vitamin D deficiency in the U.S. population. AB - BACKGROUND: Recently low dose organochlorine (OC) pesticides have been strongly linked to various chronic diseases including diabetes and cardiovascular diseases. Both field and animal studies have suggested a possibility that persistent lipophilic chemicals like OC pesticides can cause vitamin D deficiency, but there have been no human studies of exposure to any chemical as a possible cause of vitamin D deficiency. This study was performed to examine if serum concentrations of OC pesticides were associated with serum concentrations of 25-hydroxyvitamin D (25(OH)D) in the U.S. general population. METHODOLOGY/PRINCIPAL FINDINGS: Cross-sectional associations of serum OC pesticides with serum 25(OH)D were investigated in 1,275 subjects aged >=20 in the National Health and Nutrition Examination Survey (NHANES), 2003-2004. We selected 7 OC pesticides detectable in >=80% of participants. Among the 7 OC pesticides, p,p'-DDT (beta = -0.022, P<0.01), p,p'-DDE (beta = -0.018, P = 0.04), and beta-hexachlorocyclohexane (beta = -0.022, P = 0.02) showed significant inverse associations with serum 25(OH)D levels. When study subjects were stratified by age, race, and the presence of various chronic diseases, p,p'-DDT showed consistent inverse associations in all subgroups, although stronger associations tended to be observed among subjects with old age, white race, or chronic diseases. CONCLUSION/SIGNIFICANCE: The current study suggests that the background exposure to some OC pesticides leads to vitamin D deficiency in human. Considering the importance of vitamin D deficiency in the development of chronic diseases, chemical exposure as a possible cause of vitamin D deficiency should be evaluated in prospective and experimental studies. PMID- 22295073 TI - Childhood adversity and epigenetic modulation of the leukocyte glucocorticoid receptor: preliminary findings in healthy adults. AB - BACKGROUND: A history of early adverse experiences is an important risk factor for adult psychopathology. Changes in stress sensitivity and functioning of the hypothalamic-pituitary-adrenal (HPA) axis may underlie the association between stress and risk for psychiatric disorders. Preclinical work in rodents has linked low levels of maternal care to increased methylation of the promoter region of the glucocorticoid receptor (GR) gene, as well as to exaggerated hormonal and behavioral responses to stress. Recent studies have begun to examine whether early-life stress leads to epigenetic modifications of the GR gene in humans. METHODS: We examined the degree of methylation of a region of the promoter of the human GR gene (NR3C1) in leukocyte DNA from 99 healthy adults. Participants reported on their childhood experiences of parental behavior, parental death or desertion, and childhood maltreatment. On a separate day, participants completed the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test, a standardized neuroendocrine challenge test. RESULTS: Disruption or lack of adequate nurturing, as measured by parental loss, childhood maltreatment, and parental care, was associated with increased NR3C1 promoter methylation (p<.05). In addition, NR3C1 promoter methylation was linked to attenuated cortisol responses to the Dex/CRH test (p<.05). CONCLUSIONS: These findings suggest that childhood maltreatment or adversity may lead to epigenetic modifications of the human GR gene. Alterations in methylation of this gene could underlie the associations between childhood adversity, alterations in stress reactivity, and risk for psychopathology. PMID- 22295074 TI - S100A6 protein negatively regulates CacyBP/SIP-mediated inhibition of gastric cancer cell proliferation and tumorigenesis. AB - Calcyclin-binding protein (CacyBP/SIP), identified on the basis of its ability to interact with S100 proteins in a calcium-dependent manner, was previously found to inhibit the proliferation and tumorigenesis of gastric cancer cells in our laboratory. Importantly, the effects of S100 proteins on the biological behavior of CacyBP/SIP in gastric cancer remain unclear. Herein, we report the construction of eukaryotic expression vectors for wild-type CacyBP/SIP and a truncated mutant lacking the S100 protein binding domain (CacyBP/SIPDeltaS100). The expressions of the wild-type and truncated recombinant proteins were demonstrated by transfection of MKN45 gastric cancer cells. Co immunoprecipitation assays demonstrated interaction between S100A6 and wild-type CacyBP/SIP in MKN45 cells. Removal of the S100 protein binding domain dramatically reduced the affinity of CacyBP/SIP for S100 proteins as indicated by reduced co-immunoprecipitation of S100A6 by CacyBP/SIPDeltaS100. The MTT assay, FACS assay, clonogenic assay and tumor xenograft experiment were performed to assess the effect of CacyBP/SIP on cell growth and tumorigenesis in vitro and in vivo. Overexpression of CacyBP/SIP inhibited the proliferation and tumorigenesis of MKN45 gastric cancer cells; the proliferation and tumorigenesis rates were even further reduced by the expression of CacyBP/SIPDeltaS100. We also showed that S100 proteins negatively regulate CacyBP/SIP-mediated inhibition of gastric cancer cell proliferation, through an effect on beta-catenin protein expression and transcriptional activation of Tcf/LEF. Although the underlying mechanism of action requires further investigation, this study provides new insight into the interaction between S100 proteins and CacyBP/SIP, which might enrich our knowledge of S100 proteins and be helpful for our understanding of the development of gastric cancer. PMID- 22295075 TI - High-resolution melting analysis as a powerful tool to discriminate and genotype Pseudomonas savastanoi pathovars and strains. AB - Pseudomonas savastanoi is a serious pathogen of Olive, Oleander, Ash, and several other Oleaceae. Its epiphytic or endophytic presence in asymptomatic plants is crucial for the spread of Olive and Oleander knot disease, as already ascertained for P. savastanoi pv. savastanoi (Psv) on Olive and for pv. nerii (Psn) on Oleander, while no information is available for pv. fraxini (Psf) on Ash. Nothing is known yet about the distribution on the different host plants and the real host range of these pathovars in nature, although cross-infections were observed following artificial inoculations. A multiplex Real-Time PCR assay was recently developed to simultaneously and quantitatively discriminate in vitro and in planta these P. savastanoi pathovars, for routine culture confirmation and for epidemiological and diagnostical studies. Here an innovative High-Resolution Melting Analysis (HRMA)-based assay was set up to unequivocally discriminate Psv, Psn and Psf, according to several single nucleotide polymorphisms found in their Type Three Secretion System clusters. The genetic distances among 56 P. savastanoi strains belonging to these pathovars were also evaluated, confirming and refining data previously obtained by fAFLP. To our knowledge, this is the first time that HRMA is applied to a bacterial plant pathogen, and one of the few multiplex HRMA-based assays developed so far. This protocol provides a rapid, sensitive, specific tool to differentiate and detect Psv, Psn and Psf strains, also in vivo and against other related bacteria, with lower costs than conventional multiplex Real-Time PCR. Its application is particularly suitable for sanitary certification programs for P. savastanoi, aimed at avoiding the spreading of this phytopathogen through asymptomatic plants. PMID- 22295076 TI - Resolving structure and mechanical properties at the nanoscale of viruses with frequency modulation atomic force microscopy. AB - Structural Biology (SB) techniques are particularly successful in solving virus structures. Taking advantage of the symmetries, a heavy averaging on the data of a large number of specimens, results in an accurate determination of the structure of the sample. However, these techniques do not provide true single molecule information of viruses in physiological conditions. To answer many fundamental questions about the quickly expanding physical virology it is important to develop techniques with the capability to reach nanometer scale resolution on both structure and physical properties of individual molecules in physiological conditions. Atomic force microscopy (AFM) fulfills these requirements providing images of individual virus particles under physiological conditions, along with the characterization of a variety of properties including local adhesion and elasticity. Using conventional AFM modes is easy to obtain molecular resolved images on flat samples, such as the purple membrane, or large viruses as the Giant Mimivirus. On the contrary, small virus particles (25-50 nm) cannot be easily imaged. In this work we present Frequency Modulation atomic force microscopy (FM-AFM) working in physiological conditions as an accurate and powerful technique to study virus particles. Our interpretation of the so called "dissipation channel" in terms of mechanical properties allows us to provide maps where the local stiffness of the virus particles are resolved with nanometer resolution. FM-AFM can be considered as a non invasive technique since, as we demonstrate in our experiments, we are able to sense forces down to 20 pN. The methodology reported here is of general interest since it can be applied to a large number of biological samples. In particular, the importance of mechanical interactions is a hot topic in different aspects of biotechnology ranging from protein folding to stem cells differentiation where conventional AFM modes are already being used. PMID- 22295077 TI - One-step detection of the 2009 pandemic influenza A(H1N1) virus by the RT SmartAmp assay and its clinical validation. AB - BACKGROUND: In 2009, a pandemic (pdm) influenza A(H1N1) virus infection quickly circulated globally resulting in about 18,000 deaths around the world. In Japan, infected patients accounted for 16% of the total population. The possibility of human-to-human transmission of highly pathogenic novel influenza viruses is becoming a fear for human health and society. METHODOLOGY: To address the clinical need for rapid diagnosis, we have developed a new method, the "RT SmartAmp assay", to rapidly detect the 2009 pandemic influenza A(H1N1) virus from patient swab samples. The RT-SmartAmp assay comprises both reverse transcriptase (RT) and isothermal DNA amplification reactions in one step, where RNA extraction and PCR reaction are not required. We used an exciton-controlled hybridization sensitive fluorescent primer to specifically detect the HA segment of the 2009 pdm influenza A(H1N1) virus within 40 minutes without cross-reacting with the seasonal A(H1N1), A(H3N2), or B-type (Victoria) viruses. RESULTS AND CONCLUSIONS: We evaluated the RT-SmartAmp method in clinical research carried out in Japan during a pandemic period of October 2009 to January 2010. A total of 255 swab samples were collected from outpatients with influenza-like illness at three hospitals and eleven clinics located in the Tokyo and Chiba areas in Japan. The 2009 pdm influenza A(H1N1) virus was detected by the RT-SmartAmp assay, and the detection results were subsequently compared with data of current influenza diagnostic tests (lateral flow immuno-chromatographic tests) and viral genome sequence analysis. In conclusion, by the RT-SmartAmp assay we could detect the 2009 pdm influenza A(H1N1) virus in patients' swab samples even in early stages after the initial onset of influenza symptoms. Thus, the RT-SmartAmp assay is considered to provide a simple and practical tool to rapidly detect the 2009 pdm influenza A(H1N1) virus. PMID- 22295078 TI - The zeta toxin induces a set of protective responses and dormancy. AB - The zetaepsilon module consists of a labile antitoxin protein, epsilon, which in dimer form (epsilon(2)) interferes with the action of the long-living monomeric zeta phosphotransferase toxin through protein complex formation. Toxin zeta, which inhibits cell wall biosynthesis and may be bactericide in nature, at or near physiological concentrations induces reversible cessation of Bacillus subtilis proliferation (protective dormancy) by targeting essential metabolic functions followed by propidium iodide (PI) staining in a fraction (20-30%) of the population and selects a subpopulation of cells that exhibit non-inheritable tolerance (1-5*10(-5)). Early after induction zeta toxin alters the expression of ~78 genes, with the up-regulation of relA among them. RelA contributes to enforce toxin-induced dormancy. At later times, free active zeta decreases synthesis of macromolecules and releases intracellular K(+). We propose that zeta toxin induces reversible protective dormancy and permeation to PI, and expression of epsilon(2) antitoxin reverses these effects. At later times, toxin expression is followed by death of a small fraction (~10%) of PI stained cells that exited earlier or did not enter into the dormant state. Recovery from stress leads to de novo synthesis of epsilon(2) antitoxin, which blocks ATP binding by zeta toxin, thereby inhibiting its phosphotransferase activity. PMID- 22295079 TI - Colloids as mobile substrates for the implantation and integration of differentiated neurons into the mammalian brain. AB - Neuronal degeneration and the deterioration of neuronal communication lie at the origin of many neuronal disorders, and there have been major efforts to develop cell replacement therapies for treating such diseases. One challenge, however, is that differentiated cells are challenging to transplant due to their sensitivity both to being uprooted from their cell culture growth support and to shear forces inherent in the implantation process. Here, we describe an approach to address these problems. We demonstrate that rat hippocampal neurons can be grown on colloidal particles or beads, matured and even transfected in vitro, and subsequently transplanted while adhered to the beads into the young adult rat hippocampus. The transplanted cells have a 76% cell survival rate one week post surgery. At this time, most transplanted neurons have left their beads and elaborated long processes, similar to the host neurons. Additionally, the transplanted cells distribute uniformly across the host hippocampus. Expression of a fluorescent protein and the light-gated glutamate receptor in the transplanted neurons enabled them to be driven to fire by remote optical control. At 1-2 weeks after transplantation, calcium imaging of host brain slice shows that optical excitation of the transplanted neurons elicits activity in nearby host neurons, indicating the formation of functional transplant-host synaptic connections. After 6 months, the transplanted cell survival and overall cell distribution remained unchanged, suggesting that cells are functionally integrated. This approach, which could be extended to other cell classes such as neural stem cells and other regions of the brain, offers promising prospects for neuronal circuit repair via transplantation of in vitro differentiated, genetically engineered neurons. PMID- 22295080 TI - Predation and the maintenance of color polymorphism in a habitat specialist squamate. AB - Multiple studies have addressed the mechanisms maintaining polymorphism within a population. However, several examples exist where species inhabiting diverse habitats exhibit local population-specific polymorphism. Numerous explanations have been proposed for the maintenance of geographic variation in color patterns. For example, spatial variation in patterns of selection or limited gene flow can cause entire populations to become fixed for a single morph, resulting in separate populations of the same species exhibiting separate and distinct color morphs. The mottled rock rattlesnake (Crotalus lepidus lepidus) is a montane species that exhibits among-population color polymorphism that correlates with substrate color. Habitat substrate in the eastern part of its range is composed primarily of light colored limestone and snakes have light dorsal coloration, whereas in the western region the substrate is primarily dark and snakes exhibit dark dorsal coloration. We hypothesized that predation on high contrast color and blotched patterns maintain these distinct color morphs. To test this we performed a predation experiment in the wild by deploying model snakes at 12 sites evenly distributed within each of the two regions where the different morphs are found. We employed a 2*2 factorial design that included two color and two blotched treatments. Our results showed that models contrasting with substrate coloration suffered significantly more avian attacks relative to models mimicking substrates. Predation attempts on blotched models were similar in each substrate type. These results support the hypothesis that color pattern is maintained by selective predation. PMID- 22295081 TI - Highly accurate diagnosis of pleural tuberculosis by immunological analysis of the pleural effusion. AB - Pleural TB is notoriously difficult to diagnose due to its paucibacillary nature yet it is the most common cause of pleural effusions in TB endemic countries such as The Gambia. We identified both cellular and soluble biomarkers in the pleural fluid that allowed highly accurate diagnosis of pleural TB compared to peripheral blood markers. Multi-plex cytokine analysis on unstimulated pleural fluid showed that IP-10 resulted in a positive likelihood ratio (LR) of 9.6 versus 2.8 for IFN gamma; a combination of IP-10, IL-6 and IL-10 resulted in an AUC of 0.96 and positive LR of 10. A striking finding was the significantly higher proportion of PPD-specific IFN-gamma+TNF-alpha+ cell population (PPD-IGTA) in the pleural fluid compared to peripheral blood of TB subjects. Presence of this pleural PPD-IGTA population resulted in 95% correct classification of pleural TB disease with a sensitivity of 95% and specificity of 100%. These data suggest that analysis of the site of infection provides superior diagnostic accuracy compared to peripheral blood for pleural TB, likely due to the sequestration of effector cells at this acute stage of disease. PMID- 22295083 TI - Crustose coralline algae and a cnidarian neuropeptide trigger larval settlement in two coral reef sponges. AB - In sessile marine invertebrates, larval settlement is fundamental to population maintenance and persistence. Cues contributing to the settlement choices and metamorphosis of larvae have important implications for the success of individuals and populations, but cues mediating larval settlement for many marine invertebrates are largely unknown. This study assessed larval settlement in two common Great Barrier Reef sponges, Coscinoderma matthewsi and Rhopaloeides odorabile, to cues that enhance settlement and metamorphosis in various species of scleractinian coral larvae. Methanol extracts of the crustose coralline algae (CCA), Porolithon onkodes, corresponding to a range of concentrations, were used to determine the settlement responses of sponge larvae. Cnidarian neuropeptides (GLW-amide neuropeptides) were also tested as a settlement cue. Settlement in both sponge species was approximately two-fold higher in response to live chips of CCA and optimum concentrations of CCA extract compared to 0.2 um filtered sea water controls. Metamorphosis also increased when larvae were exposed to GLW amide neuropeptides; R. odorabile mean metamorphosis reached 42.0+/-5.8% compared to 16.0+/-2.4% in seawater controls and in C. matthewsi mean metamorphosis reached 68.3+/-5.4% compared to 36.7+/-3.3% in seawater controls. These results demonstrate the contributing role chemosensory communication plays in the ability of sponge larvae to identify suitable habitat for successful recruitment. It also raises the possibility that larvae from distinct phyla may share signal transduction pathways involved in metamorphosis. PMID- 22295082 TI - Nlrp2, a maternal effect gene required for early embryonic development in the mouse. AB - Maternal effect genes encode proteins that are produced during oogenesis and play an essential role during early embryogenesis. Genetic ablation of such genes in oocytes can result in female subfertility or infertility. Here we report a newly identified maternal effect gene, Nlrp2, which plays a role in early embryogenesis in the mouse. Nlrp2 mRNAs and their proteins (~118 KDa) are expressed in oocytes and granulosa cells during folliculogenesis. The transcripts show a striking decline in early preimplantation embryos before zygotic genome activation, but the proteins remain present through to the blastocyst stage. Immunogold electron microscopy revealed that the NLRP2 protein is located in the cytoplasm, nucleus and close to nuclear pores in the oocytes, as well as in the surrounding granulosa cells. Using RNA interference, we knocked down Nlrp2 transcription specifically in mouse germinal vesicle oocytes. The knockdown oocytes could progress through the metaphase of meiosis I and emit the first polar body. However, the development of parthenogenetic embryos derived from Nlrp2 knockdown oocytes mainly blocked at the 2-cell stage. The maternal depletion of Nlrp2 in zygotes led to early embryonic arrest. In addition, overexpression of Nlrp2 in zygotes appears to lead to normal development, but increases blastomere apoptosis in blastocysts. These results provide the first evidence that Nlrp2 is a member of the mammalian maternal effect genes and required for early embryonic development in the mouse. PMID- 22295084 TI - Impacts on the deep-sea ecosystem by a severe coastal storm. AB - Major coastal storms, associated with strong winds, high waves and intensified currents, and occasionally with heavy rains and flash floods, are mostly known because of the serious damage they can cause along the shoreline and the threats they pose to navigation. However, there is a profound lack of knowledge on the deep-sea impacts of severe coastal storms. Concurrent measurements of key parameters along the coast and in the deep-sea are extremely rare. Here we present a unique data set showing how one of the most extreme coastal storms of the last decades lashing the Western Mediterranean Sea rapidly impacted the deep sea ecosystem. The storm peaked the 26(th) of December 2008 leading to the remobilization of a shallow-water reservoir of marine organic carbon associated with fine particles and resulting in its redistribution across the deep basin. The storm also initiated the movement of large amounts of coarse shelf sediment, which abraded and buried benthic communities. Our findings demonstrate, first, that severe coastal storms are highly efficient in transporting organic carbon from shallow water to deep water, thus contributing to its sequestration and, second, that natural, intermittent atmospheric drivers sensitive to global climate change have the potential to tremendously impact the largest and least known ecosystem on Earth, the deep-sea ecosystem. PMID- 22295085 TI - Genetic and epigenetic alterations of the NF2 gene in sporadic vestibular schwannomas. AB - BACKGROUND: Mutations in the neurofibromatosis type 2 (NF2) tumor-suppressor gene have been identified in not only NF2-related tumors but also sporadic vestibular schwannomas (VS). This study investigated the genetic and epigenetic alterations in tumors and blood from 30 Korean patients with sporadic VS and correlated these alterations with tumor behavior. METHODOLOGY/PRINCIPAL FINDINGS: NF2 gene mutations were detected using PCR and direct DNA sequencing and three highly polymorphic microsatellite DNA markers were used to assess the loss of heterozygosity (LOH) from chromosome 22. Aberrant hypermethylation of the CpG island of the NF2 gene was also analyzed. The tumor size, the clinical growth index, and the proliferative activity assessed using the Ki-67 labeling index were evaluated. We found 18 mutations in 16 cases of 30 schwannomas (53%). The mutations included eight frameshift mutations, seven nonsense mutations, one in frame deletion, one splicing donor site, and one missense mutation. Nine patients (30%) showed allelic loss. No patient had aberrant hypermethylation of the NF2 gene and correlation between NF2 genetic alterations and tumor behavior was not observed in this study. CONCLUSIONS/SIGNIFICANCE: The molecular genetic changes in sporadic VS identified here included mutations and allelic loss, but no aberrant hypermethylation of the NF2 gene was detected. In addition, no clear genotype/phenotype correlation was identified. Therefore, it is likely that other factors contribute to tumor formation and growth. PMID- 22295086 TI - Bar-coded pyrosequencing reveals the responses of PBDE-degrading microbial communities to electron donor amendments. AB - Polybrominated diphenyl ethers (PBDEs) can be reductively degraded by microorganisms under anaerobic conditions. However, little is known about the effect of electron donors on microbial communities involved in PBDEs degradation. Here we employed 454 Titanium pyrosequencing to examine the phylogenetic diversity, composition, structure and dynamics of microbial communities from microcosms under the conditions of different electron donor amendments. The community structures in each of the five alternate electron donor enrichments were significantly shifted in comparison with those of the control microcosm. Commonly existing OTUs between the treatment and control consortia increased from 5 to 17 and more than 50% of OTUs increased around 13.7 to 186 times at least in one of the microcosms after 90-days enrichment. Although the microbial communities at different taxonomic levels were significantly changed by different environmental variable groups in redundancy analysis, significant correlations were observed between the microbial communities and PBDE congener profiles. The lesser-brominated PBDE congeners, tri-BDE congener (BDE-32) and hexa-BDE, were identified as the key factors shaping the microbial community structures at OTU level. Some rare populations, including the known dechlorinating bacterium, Dehalobacter, showed significant positive-correlation with the amounts of PBDE congeners in the consortia. The same results were also observed on some unclassified bacteria. These results suggest that PBDEs-degrading microbial communities can be successfully enriched, and their structures and compositions can be manipulated through adjusting the environmental parameters. PMID- 22295087 TI - Fast multispectral optoacoustic tomography (MSOT) for dynamic imaging of pharmacokinetics and biodistribution in multiple organs. AB - The characterization of pharmacokinetic and biodistribution profiles is an essential step in the development process of new candidate drugs or imaging agents. Simultaneously, the assessment of organ function related to the uptake and clearance of drugs is of great importance. To this end, we demonstrate an imaging platform capable of high-rate characterization of the dynamics of fluorescent agents in multiple organs using multispectral optoacoustic tomography (MSOT). A spatial resolution of approximately 150 um through mouse cross-sections allowed us to image blood vessels, the kidneys, the liver and the gall bladder. In particular, MSOT was employed to characterize the removal of indocyanine green from the systemic circulation and its time-resolved uptake in the liver and gallbladder. Furthermore, it was possible to track the uptake of a carboxylate dye in separate regions of the kidneys. The results demonstrate the acquisition of agent concentration metrics at rates of 10 samples per second at a single wavelength and 17 s per multispectral sample with 10 signal averages at each of 5 wavelengths. Overall, such imaging performance introduces previously undocumented capabilities of fast, high resolution in vivo imaging of the fate of optical agents for drug discovery and basic biological research. PMID- 22295088 TI - The kinetics of early T and B cell immune recovery after bone marrow transplantation in RAG-2-deficient SCID patients. AB - The kinetics of T and B cell immune recovery after bone marrow transplantation (BMT) is affected by many pre- and post-transplant factors. Because of the profoundly depleted baseline T and B cell immunity in recombination activating gene 2 (RAG-2)-deficient severe combined immunodeficiency (SCID) patients, some of these factors are eliminated, and the immune recovery after BMT can then be clearly assessed. This process was followed in ten SCID patients in parallel to their associated transplant-related complications. Early peripheral presence of T and B cells was observed in 8 and 4 patients, respectively. The latter correlated with pre-transplant conditioning therapy. Cells from these patients carried mainly signal joint DNA episomes, indicative of newly derived B and T cells. They were present before the normalization of the T cell receptor (TCR) and the B cell receptor (BCR) repertoire. Early presentation of the ordered TCR gene rearrangements after BMT occurred simultaneously, but this pattern was heterogeneous over time, suggesting different and individual thymic recovery processes. Our findings early after transplant could suggest the long-term patients' clinical outcome. Early peripheral presence of newly produced B and T lymphocytes from their production and maturation sites after BMT suggests donor stem cell origin rather than peripheral expansion, and is indicative of successful outcome. Peripheral detection of TCR excision circles and kappa deleting recombination excision circles in RAG-2-deficient SCID post-BMT are early markers of T and B cell reconstitution, and can be used to monitor outcome and tailor specific therapy for patients undergoing BMT. PMID- 22295089 TI - Cutaneous larva migrans among devotees of the Nallur temple in Jaffna, Sri Lanka. AB - BACKGROUND: Many cases of Cutaneous Larva Migrans (CLM) have been observed among devotees, during and immediately after the annual festival at the Nallur Hindu temple in Jaffna. OBJECTIVE: To ascertain the risk factors associated with infestation and devotees' knowledge and practices regarding the condition. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study using an interviewer administered questionnaire and observation was conducted in August 2010. Out of 200 selected devotees 194(97%) responded. Soil and dog faecal samples were collected from the temple premises and examined for the presence of nematode larva and egg respectively. Among 194 male respondents, 58.2%(95% CI: 51.2% 65.0%) had lesions of CLM. One hundred and thirty (67%) respondents performed the ritual everyday; whereas 33% did so on special days. One hundred and twelve (57.7%) participants performed the ritual before 5.00am and remaining 42.3% performed after 5.00am. Among the participants, 77(36.7%) had the similar condition in previous years. One hundred and fifty seven (80.9%) were aware about this disease and 52(27%) devotees adopted some kind of precautionary measures. Bivariate analysis showed significant association between occurrence of CLM lesions and frequency of performing the ritual (p<0.001, OR-15.1; 95% CI:7.2 32.0), the timing of ritual performance (p = 0.022, OR-1.96; 95% CI:1.10-3.52), similar condition in previous year (p<0.001, OR-6.83; 95% CI: 3.39-13.76) and previous awareness of the condition (p = 0.005; OR-0.59;95% CI:0.43-0.82). Multivariate analysis showed that the frequency of ritual performance (OR-11.75; 95% CI 5.37-25.74) and similar conditions in previous years (OR-4.71; 95% CI: 2.14-10.39) were the independent risk factors. Two of the 20 soil samples were positive for the nematode larvae and three out of five dog faeces were positive for hookworm eggs. CONCLUSIONS/SIGNIFICANCE: Deworming the stray dogs around the temple premises combined with the awareness programs among the public may be the effective and feasible precautionary measures to control similar epidemics in future. PMID- 22295090 TI - A WKYMVm-containing combination elicits potent anti-tumor activity in heterotopic cancer animal model. AB - The development of efficient anti-cancer therapy has been a topic of intense interest for several decades. Combined administration of certain molecules and immune cells has been shown to be an effective form of anti-cancer therapy. Here, we examined the effects of administering an immune stimulating peptide (WKYMVm), 5-fluoro-uracil (5-FU), and mature dendritic cells (mDCs) against heterotopic cancer animal model. Administration of the triple combination strongly reduced tumor volume in CT-26-inoculated heterotopic cancer animal model. The induced anti-tumor activity was well correlated with FAS expression, caspase-3 activation, and cancer cell apoptosis. The triple combination treatment caused recruitment of CD8 T lymphocytes and natural killer (NK) cells into the tumor. The production of two cytokines, IFN-gamma and IL-12, were strongly stimulated by administration of the triple combination. Depletion of CD8 T lymphocytes or NK cells by administration of anti-CD8 or anti-asialoGM1 antibody inhibited the anti tumor activity and cytokine production of the triple combination. The triple combination strongly inhibited metastasis of colon cancer cells in a heterotopic cancer animal model as well as in a metastatic cancer animal model, and enhanced the survival rate of the mice model. Adoptive transfer of CD8 T lymphocytes and NK cells further increased the survival rate. Taken together, we suggest that the use of triple combination therapy of WKYMVm, 5-FU, and mDCs may have implications in solid tumor and metastasis treatment. PMID- 22295091 TI - Predicting the impact of alternative splicing on plant MADS domain protein function. AB - Several genome-wide studies demonstrated that alternative splicing (AS) significantly increases the transcriptome complexity in plants. However, the impact of AS on the functional diversity of proteins is difficult to assess using genome-wide approaches. The availability of detailed sequence annotations for specific genes and gene families allows for a more detailed assessment of the potential effect of AS on their function. One example is the plant MADS-domain transcription factor family, members of which interact to form protein complexes that function in transcription regulation. Here, we perform an in silico analysis of the potential impact of AS on the protein-protein interaction capabilities of MIKC-type MADS-domain proteins. We first confirmed the expression of transcript isoforms resulting from predicted AS events. Expressed transcript isoforms were considered functional if they were likely to be translated and if their corresponding AS events either had an effect on predicted dimerisation motifs or occurred in regions known to be involved in multimeric complex formation, or otherwise, if their effect was conserved in different species. Nine out of twelve MIKC MADS-box genes predicted to produce multiple protein isoforms harbored putative functional AS events according to those criteria. AS events with conserved effects were only found at the borders of or within the K-box domain. We illustrate how AS can contribute to the evolution of interaction networks through an example of selective inclusion of a recently evolved interaction motif in the MADS AFFECTING FLOWERING1-3 (MAF1-3) subclade. Furthermore, we demonstrate the potential effect of an AS event in SHORT VEGETATIVE PHASE (SVP), resulting in the deletion of a short sequence stretch including a predicted interaction motif, by overexpression of the fully spliced and the alternatively spliced SVP transcripts. For most of the AS events we were able to formulate hypotheses about the potential impact on the interaction capabilities of the encoded MIKC proteins. PMID- 22295092 TI - Specific nuclear localizing sequence directs two myosin isoforms to the cell nucleus in calmodulin-sensitive manner. AB - BACKGROUND: Nuclear myosin I (NM1) was the first molecular motor identified in the cell nucleus. Together with nuclear actin, they participate in crucial nuclear events such as transcription, chromatin movements, and chromatin remodeling. NM1 is an isoform of myosin 1c (Myo1c) that was identified earlier and is known to act in the cytoplasm. NM1 differs from the "cytoplasmic" myosin 1c only by additional 16 amino acids at the N-terminus of the molecule. This amino acid stretch was therefore suggested to direct NM1 into the nucleus. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the mechanism of nuclear import of NM1 in detail. Using over-expressed GFP chimeras encoding for truncated NM1 mutants, we identified a specific sequence that is necessary for its import to the nucleus. This novel nuclear localization sequence is placed within calmodulin binding motif of NM1, thus it is present also in the Myo1c. We confirmed the presence of both isoforms in the nucleus by transfection of tagged NM1 and Myo1c constructs into cultured cells, and also by showing the presence of the endogenous Myo1c in purified nuclei of cells derived from knock-out mice lacking NM1. Using pull-down and co-immunoprecipitation assays we identified importin beta, importin 5 and importin 7 as nuclear transport receptors that bind NM1. Since the NLS sequence of NM1 lies within the region that also binds calmodulin we tested the influence of calmodulin on the localization of NM1. The presence of elevated levels of calmodulin interfered with nuclear localization of tagged NM1. CONCLUSIONS/SIGNIFICANCE: We have shown that the novel specific NLS brings to the cell nucleus not only the "nuclear" isoform of myosin I (NM1 protein) but also its "cytoplasmic" isoform (Myo1c protein). This opens a new field for exploring functions of this molecular motor in nuclear processes, and for exploring the signals between cytoplasm and the nucleus. PMID- 22295093 TI - Biochemical discrimination between selenium and sulfur 1: a single residue provides selenium specificity to human selenocysteine lyase. AB - Selenium and sulfur are two closely related basic elements utilized in nature for a vast array of biochemical reactions. While toxic at higher concentrations, selenium is an essential trace element incorporated into selenoproteins as selenocysteine (Sec), the selenium analogue of cysteine (Cys). Sec lyases (SCLs) and Cys desulfurases (CDs) catalyze the removal of selenium or sulfur from Sec or Cys and generally act on both substrates. In contrast, human SCL (hSCL) is specific for Sec although the only difference between Sec and Cys is the identity of a single atom. The chemical basis of this selenium-over-sulfur discrimination is not understood. Here we describe the X-ray crystal structure of hSCL and identify Asp146 as the key residue that provides the Sec specificity. A D146K variant resulted in loss of Sec specificity and appearance of CD activity. A dynamic active site segment also provides the structural prerequisites for direct product delivery of selenide produced by Sec cleavage, thus avoiding release of reactive selenide species into the cell. We thus here define a molecular determinant for enzymatic specificity discrimination between a single selenium versus sulfur atom, elements with very similar chemical properties. Our findings thus provide molecular insights into a key level of control in human selenium and selenoprotein turnover and metabolism. PMID- 22295094 TI - Mutational robustness of gene regulatory networks. AB - Mutational robustness of gene regulatory networks refers to their ability to generate constant biological output upon mutations that change network structure. Such networks contain regulatory interactions (transcription factor-target gene interactions) but often also protein-protein interactions between transcription factors. Using computational modeling, we study factors that influence robustness and we infer several network properties governing it. These include the type of mutation, i.e. whether a regulatory interaction or a protein-protein interaction is mutated, and in the case of mutation of a regulatory interaction, the sign of the interaction (activating vs. repressive). In addition, we analyze the effect of combinations of mutations and we compare networks containing monomeric with those containing dimeric transcription factors. Our results are consistent with available data on biological networks, for example based on evolutionary conservation of network features. As a novel and remarkable property, we predict that networks are more robust against mutations in monomer than in dimer transcription factors, a prediction for which analysis of conservation of DNA binding residues in monomeric vs. dimeric transcription factors provides indirect evidence. PMID- 22295095 TI - Opposite influence of perceptual memory on initial and prolonged perception of sensory ambiguity. AB - Observers continually make unconscious inferences about the state of the world based on ambiguous sensory information. This process of perceptual decision making may be optimized by learning from experience. We investigated the influence of previous perceptual experience on the interpretation of ambiguous visual information. Observers were pre-exposed to a perceptually stabilized sequence of an ambiguous structure-from-motion stimulus by means of intermittent presentation. At the subsequent re-appearance of the same ambiguous stimulus perception was initially biased toward the previously stabilized perceptual interpretation. However, prolonged viewing revealed a bias toward the alternative perceptual interpretation. The prevalence of the alternative percept during ongoing viewing was largely due to increased durations of this percept, as there was no reliable decrease in the durations of the pre-exposed percept. Moreover, the duration of the alternative percept was modulated by the specific characteristics of the pre-exposure, whereas the durations of the pre-exposed percept were not. The increase in duration of the alternative percept was larger when the pre-exposure had lasted longer and was larger after ambiguous pre exposure than after unambiguous pre-exposure. Using a binocular rivalry stimulus we found analogous perceptual biases, while pre-exposure did not affect eye-bias. We conclude that previously perceived interpretations dominate at the onset of ambiguous sensory information, whereas alternative interpretations dominate prolonged viewing. Thus, at first instance ambiguous information seems to be judged using familiar percepts, while re-evaluation later on allows for alternative interpretations. PMID- 22295096 TI - Genetic variations in IL28B and allergic disease in children. AB - Environmental changes affecting the relationship between the developing immune system and microbial exposure have been implicated in the epidemic rise of allergic disease in developed countries. While early developmental differences in T cell function are well-recognised, there is now emerging evidence that this is related to developmental differences in innate immune function. In this study we sought to examine if differences associated with innate immunity contribute to the altered immune programming recognised in allergic children. Here, we describe for the first time, the association of carriage of the T allele of the tagging single nucleotide polymorphism rs12979860 3 kb upstream of IL28B, encoding the potent innate immune modulator type III interferon lambda (IFN-lambda3), and allergy in children (p = 0.004; OR 4.56). Strikingly, the association between rs12979860 genotype and allergic disease is enhanced in girls. Furthermore, carriage of the T allele at rs12979860 correlates with differences in the pro inflammatory profile during the first five years of life suggesting this contributes to the key differences in subsequent innate immune development in children who develop allergic disease. In the context of rising rates of disease, these immunologic differences already present at birth imply very early interaction between genetic predisposition and prenatal environmental influences. PMID- 22295097 TI - The 18 kDa translocator protein (peripheral benzodiazepine receptor) expression in the bone of normal, osteoprotegerin or low calcium diet treated mice. AB - The presence of the translocator protein (TSPO), previously named as the mitochondrial or peripheral benzodiazepine receptor, in bone cells was studied in vitro and in situ using RT-qPCR, and receptor autoradiography using the selective TSPO ligand PK11195.In vitro, the TSPO is highly expressed in osteoblastic and osteoclastic cells.In situ, constitutive expression of TSPO is found in bone marrow and trabecular bone, e.g., spongiosa. Mice with a reduction of bone turnover induced by a 4-day treatment of osteoprotegerin reduces [(3)H]PK11195 binding in the spongiosa (320+/-128 Bq x mg(-1), 499+/-106 Bq x mg(-1) in saline treated controls). In contrast, mice with an increase in bone turnover caused by a 4-day low calcium diet increases [(3)H]PK11195 binding in the spongiosa (615+/ 90 Bq x mg(-1)). Further, our study includes technical feasibility data on [(18)F]fluoride microPET imaging of rodent bone with altered turnover. Despite [(18)F]fluoride having high uptake, the in vivo signal differences were small. Using a phantom model, we describe the spillover effect and partial volume loss that affect the quantitative microPET imaging of the small bone structures in experimental mouse models. In summary, we demonstrate the expression of TSPO in small rodent bone tissues, including osteoblasts and osteoclasts. A trend increase in TSPO expression was observed in the spongiosa from low to high bone turnover conditions. However, despite the potential utility of TSPO expression as an in vivo biomarker of bone turnover in experimental rodent models, our small animal PET imaging data using [(18)F]fluoride show that even under the condition of a good biological signal-to-noise ratio and high tracer uptake, the currently achievable instrument sensitivity and spatial resolution is unlikely to be sufficient to detect subtle differences in small structures, such as mouse bone. PMID- 22295098 TI - MicroRNA-152 mediates DNMT1-regulated DNA methylation in the estrogen receptor alpha gene. AB - BACKGROUND: Estrogen receptor alpha (ERalpha) has been shown to protect against atherosclerosis. Methylation of the ERalpha gene can reduce ERalpha expression leading to a higher risk for cardiovascular disease. Recently, microRNAs have been found to regulate DNA methyltransferases (DNMTs) and thus control methylation status in several genes. We first searched for microRNAs involved in DNMT-associated DNA methylation in the ERalpha gene. We also tested whether statin and a traditional Chinese medicine (San-Huang-Xie-Xin-Tang, SHXXT) could exert a therapeutic effect on microRNA, DNMT and ERalpha methylation. METHODOLOGY/PRINCIPAL FINDINGS: The ERalpha expression was decreased and ERalpha methylation was increased in LPS-treated human aortic smooth muscle cells (HASMCs) and the aorta from rats under a high-fat diet. MicroRNA-152 was found to be down regulated in the LPS-treated HASMCs. We validated that microRNA-152 can knock down DNMT1 in HASMCs leading to hypermethylation of the ERalpha gene. Statin had no effect on microRNA-152, DNMT1 or ERalpha expression. On the contrary, SHXXT could restore microRNA-152, decrease DNMT1 and increase ERalpha expression in both cellular and animal studies. CONCLUSIONS/SIGNIFICANCE: The present study showed that microRNA-152 decreases under the pro-atherosclerotic conditions. The reduced microRNA-152 can lose an inhibitory effect on DNA methyltransferase, which leads to hypermethylation of the ERalpha gene and a decrease of ERalpha level. Although statin can not reverse these cascade proatherosclerotic changes, the SHXXT shows a promising effect to inhibit this unwanted signaling pathway. PMID- 22295099 TI - Ablation of NG2 proteoglycan leads to deficits in brown fat function and to adult onset obesity. AB - Obesity is a major health problem worldwide. We are studying the causes and effects of obesity in C57Bl/6 mice following genetic ablation of NG2, a chondroitin sulfate proteoglycan widely expressed in progenitor cells and also in adipocytes. Although global NG2 ablation delays early postnatal adipogenesis in mouse skin, adult NG2 null mice are paradoxically heavier than wild-type mice, exhibiting larger white fat deposits. This adult onset obesity is not due to NG2 dependent effects on CNS function, since specific ablation of NG2 in oligodendrocyte progenitors yields the opposite phenotype; i.e. abnormally lean mice. Metabolic analysis reveals that, while activity and food intake are unchanged in global NG2 null mice, O(2) consumption and CO(2) production are decreased, suggesting a decrease in energy expenditure. Since brown fat plays important roles in regulating energy expenditure, we have investigated brown fat function via cold challenge and high fat diet feeding, both of which induce the adaptive thermogenesis that normally occurs in brown fat. In both tests, body temperatures in NG2 null mice are reduced compared to wild-type mice, indicating a deficit in brown fat function in the absence of NG2. In addition, adipogenesis in NG2 null brown pre-adipocytes is dramatically impaired compared to wild-type counterparts. Moreover, mRNA levels for PR domain containing 16 (PRDM16) and peroxisome proliferator-activated receptor gamma coactivator (PGC)1-alpha, proteins important for brown adipocyte differentiation, are decreased in NG2 null brown fat deposits in vivo and NG2 null brown pre-adipocytes in vitro. Altogether, these results indicate that brown fat dysfunction in NG2 null mice results from deficits in the recruitment and/or development of brown pre adipocytes. As a consequence, obesity in NG2 null mice may occur due to disruptions in brown fat-dependent energy homeostasis, with resulting effects on lipid storage in white adipocytes. PMID- 22295100 TI - Translocations as experiments in the ecological resilience of an asocial mega herbivore. AB - Species translocations are remarkable experiments in evolutionary ecology, and increasingly critical to biodiversity conservation. Elaborate socio-ecological hypotheses for translocation success, based on theoretical fitness relationships, are untested and lead to complex uncertainty rather than parsimonious solutions. We used an extraordinary 89 reintroduction and 102 restocking events releasing 682 black rhinoceros (Diceros bicornis) to 81 reserves in southern Africa (1981 2005) to test the influence of interacting socio-ecological and individual characters on post-release survival. We predicted that the socio-ecological context should feature more prominently after restocking than reintroduction because released rhinoceros interact with resident conspecifics. Instead, an interaction between release cohort size and habitat quality explained reintroduction success but only individuals' ages explained restocking outcomes. Achieving translocation success for many species may not be as complicated as theory suggests. Black rhino, and similarly asocial generalist herbivores without substantial predators, are likely to be resilient to ecological challenges and robust candidates for crisis management in a changing world. PMID- 22295101 TI - LDL receptor knock-out mice are a physiological model particularly vulnerable to study the onset of inflammation in non-alcoholic fatty liver disease. AB - BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) involves steatosis combined with inflammation, which can progress into fibrosis and cirrhosis. Exploring the molecular mechanisms of NASH is highly dependent on the availability of animal models. Currently, the most commonly used animal models for NASH imitate particularly late stages of human disease. Thus, there is a need for an animal model that can be used for investigating the factors that potentiate the inflammatory response within NASH. We have previously shown that 7 day high-fat-high-cholesterol (HFC) feeding induces steatosis and inflammation in both APOE2ki and Ldlr(-/-) mice. However, it is not known whether the early inflammatory response observed in these mice will sustain over time and lead to liver damage. We hypothesized that the inflammatory response in both models is sufficient to induce liver damage over time. METHODS: APOE2ki and Ldlr(-/-) mice were fed a chow or HFC diet for 3 months. C57Bl6/J mice were used as control. RESULTS: Surprisingly, hepatic inflammation was abolished in APOE2ki mice, while it was sustained in Ldlr(-/-) mice. In addition, increased apoptosis and hepatic fibrosis was only demonstrated in Ldlr(-/-) mice. Finally, bone-marrow-derived macrophages of Ldlr(-/-) mice showed an increased inflammatory response after oxidized LDL (oxLDL) loading compared to APOE2ki mice. CONCLUSION: Ldlr(-/-) mice, but not APOE2ki mice, developed sustained hepatic inflammation and liver damage upon long term HFC feeding due to increased sensitivity for oxLDL uptake. Therefore, the Ldlr(-/-) mice are a promising physiological model particularly vulnerable for investigating the onset of hepatic inflammation in non-alcoholic steatohepatitis. PMID- 22295102 TI - Hypothalamic deep brain stimulation reduces weight gain in an obesity-animal model. AB - Prior studies of appetite regulatory networks, primarily in rodents, have established that targeted electrical stimulation of ventromedial hypothalamus (VMH) can alter food intake patterns and metabolic homeostasis. Consideration of this method for weight modulation in humans with severe overeating disorders and morbid obesity can be further advanced by modeling procedures and assessing endpoints that can provide preclinical data on efficacy and safety. In this study we adapted human deep brain stimulation (DBS) stereotactic methods and instrumentation to demonstrate in a large animal model the modulation of weight gain with VMH-DBS. Female Gottingen minipigs were used because of their dietary habits, physiologic characteristics, and brain structures that resemble those of primates. Further, these animals become obese on extra-feeding regimens. DBS electrodes were first bilaterally implanted into the VMH of the animals (n = 8) which were then maintained on a restricted food regimen for 1 mo following the surgery. The daily amount of food was then doubled for the next 2 mo in all animals to produce obesity associated with extra calorie intake, with half of the animals (n = 4) concurrently receiving continuous low frequency (50 Hz) VMH-DBS. Adverse motoric or behavioral effects were not observed subsequent to the surgical procedure or during the DBS period. Throughout this 2 mo DBS period, all animals consumed the doubled amount of daily food. However, the animals that had received VMH-DBS showed a cumulative weight gain (6.1+/-0.4 kg; mean +/- SEM) that was lower than the nonstimulated VMH-DBS animals (9.4+/-1.3 kg; p<0.05), suggestive of a DBS-associated increase in metabolic rate. These results in a porcine obesity model demonstrate the efficacy and behavioral safety of a low frequency VMH-DBS application as a potential clinical strategy for modulation of body weight. PMID- 22295103 TI - Calcimimetic R-568 and its enantiomer S-568 increase nitric oxide release in human endothelial cells. AB - BACKGROUND: Calcimimetics, such as R-568, are thought to activate G protein linked Ca(2+)-sensing receptor (CaSR) by allosterically increasing the affinity of the receptor for Ca(2+) allowing for efficient control of uremic hyperparathyroidism. Several recent studies suggest they possess additional vascular actions. Although it has been postulated that calcimimetics may have a direct effect on CaSR in the blood vessels, further studies are needed to elucidate their vascular CaSR-dependent versus CaSR-independent effects. METHODOLOGY/PRINCIPAL FINDINGS: Focusing on human umbilical vein endothelial cells (HUVECs), we studied the CaSR expression and distribution by Immunofluorescence and Western Blot analysis. CaSR function was evaluated by measuring the potential effect of calcimimetic R-568 and its enantiomer S-568 upon the modulation of intracellular Ca(2+) levels (using a single cell approach and FURA-2AM), in the presence or absence of Calhex-231, a negative modulator of CaSR. To address their potential vascular functions, we also evaluated R- and S 568-stimulated enzymatic release of Nitric Oxide (NO) by DAF-2DA, by Nitric Oxide Synthase (NOS) radiometric assay (both in HUVECs and in Human Aortic Endothelial Cells) and by measuring eNOS-ser1177 phosphorylation levels (Immunoblotting). We show that, although the CaSR protein was expressed in HUVECs, it was mainly distributed in cytoplasm while the functional CaSR dimers, usually localized on the plasma membrane, were absent. In addition, regardless of the presence or absence of Calhex-231, both R- and S-568 significantly increased intracellular Ca(2+) levels by mobilization of Ca(2+) from intracellular stores, which in turn augmented NO release by a time- and Ca(2+)-dependent increase in eNOS-ser1177 phosphorylation levels. CONCLUSIONS/SIGNIFICANCE: Taken together, these data indicate that in human endothelium there is no stereoselectivity in the responses to calcimimetics and that CaSR is probably not involved in the action of R- and S 568. This suggests an additional mechanism in support of the CaSR-independent role of calcimimetics as vasculotrope agents. PMID- 22295104 TI - Link between intestinal CD36 ligand binding and satiety induced by a high protein diet in mice. AB - CD36 is a ubiquitous membrane glycoprotein that binds long-chain fatty acids. The presence of a functional CD36 is required for the induction of satiety by a lipid load and its role as a lipid receptor driving cellular signal has recently been demonstrated. Our project aimed to further explore the role of intestinal CD36 in the regulation of food intake. Duodenal infusions of vehicle or sulfo-N succinimidyl-oleate (SSO) was performed prior to acute infusions of saline or Intralipid (IL) in mice. Infusion of minute quantities of IL induced a decrease in food intake (FI) compared to saline. Infusion of SSO had the same effect but no additive inhibitory effect was observed in presence of IL. No IL- or SSO mediated satiety occurred in CD36-null mice. To determine whether the CD36 mediated hypophagic effect of lipids was maintained in animals fed a satietogen diet, mice were subjected to a High-Protein diet (HPD). Concomitantly with the satiety effect, a rise in intestinal CD36 gene expression was observed. No satiety effect occurred in CD36-null mice. HPD-fed WT mice showed a diminished FI compared to control mice, after saline duodenal infusion. But there was no further decrease after lipid infusion. The lipid-induced decrease in FI observed on control mice was accompanied by a rise in jejunal oleylethanolamide (OEA). Its level was higher in HPD-fed mice than in controls after saline infusion and was not changed by lipids. Overall, we demonstrate that lipid binding to intestinal CD36 is sufficient to produce a satiety effect. Moreover, it could participate in the satiety effect induced by HPD. Intestine can modulate FI by several mechanisms including an increase in OEA production and CD36 gene expression. Furthermore, intestine of mice adapted to HPD have a diminished capacity to modulate their food intake in response to dietary lipids. PMID- 22295105 TI - The increased expression of integrin alpha6 (ITGA6) enhances drug resistance in EVI1(high) leukemia. AB - Ecotropic viral integration site-1 (EVI1) is one of the candidate oncogenes for human acute myeloid leukemia (AML) with chromosomal alterations at 3q26. High EVI1 expression (EVI1(high)) is a risk factor for AML with poor outcome. Using DNA microarray analysis, we previously identified that integrin alpha6 (ITGA6) was upregulated over 10-fold in EVI1(high) leukemia cells. In this study, we determined whether the increased expression of ITGA6 is associated with drug resistance and increased cell adhesion, resulting in poor prognosis. To this end, we first confirmed the expression pattern of a series of integrin genes using semi-quantitative PCR and fluorescence-activated cell sorter (FACS) analysis and determined the cell adhesion ability in EVI1(high) leukemia cells. We found that the adhesion ability of EVI1(high) leukemia cells to laminin increased with the increased expression of ITGA6 and integrin beta4 (ITGB4). The introduction of small-hairpin RNA against EVI1 (shEVI1) into EVI1(high) leukemia cells reduced the cell adhesion ability and downregulated the expression of ITGA6 and ITGB4. In addition, the overexpression of EVI1 in EVI1(low) leukemia cells enhanced their cell adhesion ability and increased the expression of ITGA6 and ITGB4. In a subsequent experiment, the introduction of shRNA against ITGA6 or ITGB4 into EVI1(high) AML cells downregulated their cell adhesion ability; however, the EVI1(high) AML cells transfected with shRNA against ITGA6 could not be maintained in culture. Moreover, treating EVI1(high) leukemia cells with neutralizing antibodies against ITGA6 or ITGB4 resulted in an enhanced responsiveness to anti cancer drugs and a reduction of their cell adhesion ability. The expression of ITGA6 is significantly elevated in cells from relapsed and EVI1(high) AML cases; therefore, ITGA6 might represent an important therapeutic target for both refractory and EVI1(high) AML. PMID- 22295106 TI - Overtime work as a predictor of major depressive episode: a 5-year follow-up of the Whitehall II study. AB - BACKGROUND: The association between overtime work and depression is still unclear. This study examined the association between overtime work and the onset of a major depressive episode (MDE). METHODOLOGY/PRINCIPAL FINDINGS: Prospective cohort study with a baseline examination of working hours, psychological morbidity (an indicator of baseline depression) and depression risk factors in 1991-1993 and a follow-up of major depressive episode in 1997-1999 (mean follow up 5.8 years) among British civil servants (the Whitehall II study; 1626 men, 497 women, mean age 47 years at baseline). Onset of 12-month MDE was assessed by the Composite International Diagnostic Interview (CIDI) at follow-up. In prospective analysis of participants with no psychological morbidity at baseline, the odds ratio for a subsequent major depressive episode was 2.43 (95% confidence interval 1.11 to 5.30) times higher for those working 11+ hours a day compared to employees working 7-8 hours a day, when adjusted for socio-demographic factors at baseline. Further adjustment for chronic physical disease, smoking, alcohol use, job strain and work-related social support had little effect on this association (odds ratio 2.52; 95% confidence interval 1.12 to 5.65). CONCLUSIONS/SIGNIFICANCE: Data from middle-aged civil servants suggest that working long hours of overtime may predispose to major depressive episodes. PMID- 22295107 TI - Alternate estrogen receptors promote invasion of inflammatory breast cancer cells via non-genomic signaling. AB - Although Inflammatory Breast Cancer (IBC) is a rare and an aggressive type of locally advanced breast cancer with a generally worst prognosis, little work has been done in identifying the status of non-genomic signaling in the invasiveness of IBC. The present study was performed to explore the status of non-genomic signaling as affected by various estrogenic and anti-estrogenic agents in IBC cell lines SUM149 and SUM190. We have identified the presence of estrogen receptor alpha (ERalpha) variant, ERalpha36 in SUM149 and SUM190 cells. This variant as well as ERbeta was present in a substantial concentration in IBC cells. The treatment with estradiol (E2), anti-estrogenic agents 4 hydroxytamoxifen and ICI 182780, ERbeta specific ligand DPN and GPR30 agonist G1 led to a rapid activation of p-ERK1/2, suggesting the involvement of ERalpha36, ERbeta and GPR30 in the non-genomic signaling pathway in these cells. We also found a substantial increase in the cell migration and invasiveness of SUM149 cells upon the treatment with these ligands. Both basal and ligand-induced migration and invasiveness of SUM149 cells were drastically reduced in the presence of MEK inhibitor U0126, implicating that the phosphorylation of ERK1/2 by MEK is involved in the observed motility and invasiveness of IBC cells. We also provide evidence for the upregulation of p-ERK1/2 through immunostaining in IBC patient samples. These findings suggest a role of non-genomic signaling through the activation of p-ERK1/2 in the hormonal dependence of IBC by a combination of estrogen receptors. These findings only explain the failure of traditional anti-estrogen therapies in ER-positive IBC which induces the non genomic signaling, but also opens newer avenues for design of modified therapies targeting these estrogen receptors. PMID- 22295108 TI - A comparative study of gene-expression data of basal cell carcinoma and melanoma reveals new insights about the two cancers. AB - A comparative analysis of genome-scale transcriptomic data of two types of skin cancers, melanoma and basal cell carcinoma in comparison with other cancer types, was conducted with the aim of identifying key regulatory factors that either cause or contribute to the aggressiveness of melanoma, while basal cell carcinoma generally remains a mild disease. Multiple cancer-related pathways such as cell proliferation, apoptosis, angiogenesis, cell invasion and metastasis, are considered, but our focus is on energy metabolism, cell invasion and metastasis pathways. Our findings include the following. (a) Both types of skin cancers use both glycolysis and increased oxidative phosphorylation (electron transfer chain) for their energy supply. (b) Advanced melanoma shows substantial up-regulation of key genes involved in fatty acid metabolism (beta-oxidation) and oxidative phosphorylation, with aerobic metabolism being far more efficient than anaerobic glycolysis, providing a source of the energetics necessary to support the rapid growth of this cancer. (c) While advanced melanoma is similar to pancreatic cancer in terms of the activity level of genes involved in promoting cell invasion and metastasis, the main metastatic form of basal cell carcinoma is substantially reduced in this activity, partially explaining why this cancer type has been considered as far less aggressive. Our method of using comparative analyses of transcriptomic data of multiple cancer types focused on specific pathways provides a novel and highly effective approach to cancer studies in general. PMID- 22295109 TI - The problem of shot selection in basketball. AB - In basketball, every time the offense produces a shot opportunity the player with the ball must decide whether the shot is worth taking. In this article, I explore the question of when a team should shoot and when they should pass up the shot by considering a simple theoretical model of the shot selection process, in which the quality of shot opportunities generated by the offense is assumed to fall randomly within a uniform distribution. Within this model I derive an answer to the question "how likely must the shot be to go in before the player should take it?" and I show that this lower cutoff for shot quality f depends crucially on the number n of shot opportunities remaining (say, before the shot clock expires), with larger n demanding that only higher-quality shots should be taken. The function f(n) is also derived in the presence of a finite turnover rate and used to predict the shooting rate of an optimal-shooting team as a function of time. The theoretical prediction for the optimal shooting rate is compared to data from the National Basketball Association (NBA). The comparison highlights some limitations of the theoretical model, while also suggesting that NBA teams may be overly reluctant to shoot the ball early in the shot clock. PMID- 22295110 TI - Early natural stimulation through environmental enrichment accelerates neuronal development in the mouse dentate gyrus. AB - The dentate gyrus is the primary afferent into the hippocampal formation, with important functions in learning and memory. Granule cells, the principle neuronal type in the dentate gyrus, are mostly formed postnatally, in a process that continues into adulthood. External stimuli, including environmental enrichment, voluntary exercise and learning, have been shown to significantly accelerate the generation and maturation of dentate granule cells in adult rodents. Whether, and to what extent, such environmental stimuli regulate the development and maturation of dentate granule cells during early postnatal development is largely unknown. Furthermore, whether natural stimuli affect the synaptic properties of granule cells had been investigated neither in newborn neurons of the adult nor during early development. To examine the effect of natural sensory stimulation on the dentate gyrus, we reared newborn mice in an enriched environment (EE). Using immunohistochemistry, we showed that dentate granule cells from EE-reared mice exhibited earlier morphological maturation, manifested as faster peaking of doublecortin expression and elevated expression of mature neuronal markers (including NeuN, calbindin and MAP2) at the end of the second postnatal week. Also at the end of the second postnatal week, we found increased density of dendritic spines across the entire dentate gyrus, together with elevated levels of postsynaptic scaffold (post-synaptic density 95) and receptor proteins (GluR2 and GABA(A)Rgamma2) of excitatory and inhibitory synapses. Furthermore, dentate granule cells of P14 EE-reared mice had lower input resistances and increased glutamatergic and GABAergic synaptic inputs. Together, our results demonstrate that EE-rearing promotes morphological and electrophysiological maturation of dentate granule cells, underscoring the importance of natural environmental stimulation on development of the dentate gyrus. PMID- 22295111 TI - Increased intratumoral neutrophil in colorectal carcinomas correlates closely with malignant phenotype and predicts patients' adverse prognosis. AB - BACKGROUND: Substantial evidence suggests that the presence of inflammatory cells plays a critical role in the development and/or progression of human tumors. Neutrophils are the common inflammatory cells in tumors; however, the infiltration of intratumoral neutrophils in colorectal carcinoma (CRC) and its effect on CRC patients' prognosis are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the methods of tissue microarray and immunohistochemistry (IHC) were used to investigate the prognostic significance of intratumoral CD66b+ neutrophil in CRC. According to receiver operating characteristic curve analysis, the cutoff score for high intratumoral CD66b+ neutrophil in CRC was defined when the mean counts were more than 60 per TMA spot. In our study, high intratumoral CD66b+ neutrophil was observed in 104/229 (45.4%) of CRCs and in 29/229 (12.7%) of adjacent mucosal tissues. Further correlation analysis showed that high intratumoral neutrophil was positively correlated with pT status, pM status and clinical stage (P<0.05). In univariate survival analysis, a significant association between high intratumoral neutrophil and shortened patients' survival was found (P<0.0001). In different subsets of CRC patients, intratumoral neutrophil was also a prognostic indicator in patients with stage II, stage III, grade 2, grade 3, pT1, pT2, pN0 and pN1 (P<0.05). Importantly, high intratumoral neutrophil was evaluated as an independent prognostic factor in multivariate analysis (P<0.05). CONCLUSIONS/SIGNIFICANCE: Our results provide evidence that increased intratumoral neutrophil in CRC may be important in the acquisition of a malignant phenotype, indicating that the presence of intratumoral neutrophil is an independent factor for poor prognosis of patients with CRC. PMID- 22295112 TI - Effects of lycopene on the initial state of atherosclerosis in New Zealand White (NZW) rabbits. AB - BACKGROUND: Lycopene is the main carotenoid in tomatoes, where it is found in high concentrations. Strong epidemiological evidence suggests that lycopene may provide protection against cardiovascular diseases. We therefore studied the effects of lycopene on diet-induced increase in serum lipid levels and the initiation of atherosclerosis in New Zealand White (NZW) rabbits. METHODOLOGY/PRINCIPAL FINDINGS: The animals, divided into four groups of 9 animals each, were fed either a standard diet, a high-cholesterol diet containing 0.5% cholesterol, a high-cholesterol diet containing placebo beadlets, or a high cholesterol diet plus 5 mg/kg body weight/day of lycopene (in the form of lycopene beadlets), for a period of 4 weeks. We found significantly elevated lycopene plasma levels in the animal group treated with lycopene beadlets. Compared to the high-cholesterol and the placebo group, this was associated with a significant reduction of 50% in total cholesterol and LDL cholesterol serum levels in the lycopene group. The amount of cholesteryl ester in the aorta was significantly decreased by lycopene. However, we did not observe a significant decrease in the extent of aortic surface lipid accumulation in the lycopene group. In addition, no differences in the intima-media thickness among groups were observed. Endothelial-dependent and endothelial-independent vasodilation in isolated rabbit aortic and carotid rings did not differ among any of the animal groups. CONCLUSIONS: Lycopene supplementation for 4 weeks increased lycopene plasma levels in the animals. Although we found strongly reduced total and LDL cholesterol serum levels as well as significantly lower amounts of cholesteryl ester in the aortae in the lycopene-treated group, no significant differences in initial lesions in the aortae were detected. PMID- 22295113 TI - Moving your sons to safety: galls containing male fig wasps expand into the centre of figs, away from enemies. AB - Figs are the inflorescences of fig trees (Ficus spp., Moraceae). They are shaped like a hollow ball, lined on their inner surface by numerous tiny female flowers. Pollination is carried out by host-specific fig wasps (Agaonidae). Female pollinators enter the figs through a narrow entrance gate and once inside can walk around on a platform generated by the stigmas of the flowers. They lay their eggs into the ovules, via the stigmas and styles, and also gall the flowers, causing the ovules to expand and their pedicels to elongate. A single pollinator larva develops in each galled ovule. Numerous species of non-pollinating fig wasps (NPFW, belonging to other families of Chalcidoidea) also make use of galled ovules in the figs. Some initiate galls, others make use of pollinator-generated galls, killing pollinator larvae. Most NPFW oviposit from the outside of figs, making peripherally-located pollinator larvae more prone to attack. Style length variation is high among monoecious Ficus spp. and pollinators mainly oviposit into more centrally-located ovules, with shorter styles. Style length variation is lower in male (wasp-producing) figs of dioecious Ficus spp., making ovules equally vulnerable to attack by NPFW at the time that pollinators oviposit. We recorded the spatial distributions of galled ovules in mature male figs of the dioecious Ficus hirta in Southern China. The galls contained pollinators and three NPFW that kill them. Pollinators were concentrated in galls located towards the centre of the figs, NPFW towards the periphery. Due to greater pedicel elongation by male galls, male pollinators became located in more central galls than their females, and so were less likely to be attacked. This helps ensure that sufficient males survive, despite strongly female-biased sex ratios, and may be a consequence of the pollinator females laying mostly male eggs at the start of oviposition sequences. PMID- 22295114 TI - Progesterone inhibits epithelial-to-mesenchymal transition in endometrial cancer. AB - BACKGROUND: Every year approximately 74,000 women die of endometrial cancer, mainly due to recurrent or metastatic disease. The presence of tumor infiltrating lymphocytes (TILs) as well as progesterone receptor (PR) positivity has been correlated with improved prognosis. This study describes two mechanisms by which progesterone inhibits metastatic spread of endometrial cancer: by stimulating T cell infiltration and by inhibiting epithelial-to-mesenchymal cell transition (EMT). METHODOLOGY AND PRINCIPAL FINDINGS: Paraffin sections from patients with (n = 9) or without (n = 9) progressive endometrial cancer (recurrent or metastatic disease) were assessed for the presence of CD4+ (helper), CD8+ (cytotoxic) and Foxp3+ (regulatory) T-lymphocytes and PR expression. Progressive disease was observed to be associated with significant loss of TILs and loss of PR expression. Frozen tumor samples, used for genome-wide expression analysis, showed significant regulation of pathways involved in immunesurveillance, EMT and metastasis. For a number of genes, such as CXCL14, DKK1, DKK4, PEG10 and WIF1, quantitive RT-PCR was performed to verify up- or downregulation in progressive disease. To corroborate the role of progesterone in regulating invasion, Ishikawa (IK) endometrial cancer cell lines stably transfected with PRA (IKPRA), PRB (IKPRB) and PRA+PRB (IKPRAB) were cultured in presence/absence of progesterone (MPA) and used for genome-wide expression analysis, Boyden- and wound healing migration assays, and IHC for known EMT markers. IKPRB and IKPRAB cell lines showed MPA induced inhibition of migration and loss of the mesenchymal marker vimentin at the invasive front of the wound healing assay. Furthermore, pathway analysis of significantly MPA regulated genes showed significant down regulation of important pathways involved in EMT, immunesuppression and metastasis: such as IL6-, TGF-beta and Wnt/beta-catenin signaling. CONCLUSION: Intact progesterone signaling in non-progressive endometrial cancer seems to be an important factor stimulating immunosurveilance and inhibiting transition from an epithelial to a more mesenchymal, more invasive phenotype. PMID- 22295115 TI - Maternal use of antibiotics, hospitalisation for infection during pregnancy, and risk of childhood epilepsy: a population-based cohort study. AB - BACKGROUND: Maternal infection during pregnancy may be a risk factor for epilepsy in offspring. Use of antibiotics is a valid marker of infection. METHODOLOGY/PRINCIPAL FINDINGS: To examine the relationship between maternal infection during pregnancy and risk of childhood epilepsy we conducted a historical cohort study of singletons born in northern Denmark from 1998 through 2008 who survived >=29 days. We used population-based medical databases to ascertain maternal use of antibiotics or hospital contacts with infection during pregnancy, as well as first-time hospital contacts with a diagnosis of epilepsy among offspring. We compared incidence rates (IR) of epilepsy among children of mothers with and without infection during pregnancy. We examined the outcome according to trimester of exposure, type of antibiotic, and total number of prescriptions, using Poisson regression to estimate incidence rate ratios (IRRs) while adjusting for covariates. Among 191,383 children in the cohort, 948 (0.5%) were hospitalised or had an outpatient visit for epilepsy during follow-up, yielding an IR of 91 per 100 000 person-years (PY). The five-year cumulative incidence of epilepsy was 4.5 per 1000 children. Among children exposed prenatally to maternal infection, the IR was 117 per 100,000 PY, with an adjusted IRR of 1.40 (95% confidence interval (CI): 1.22-1.61), compared with unexposed children. The association was unaffected by trimester of exposure, antibiotic type, or prescription count. CONCLUSIONS/SIGNIFICANCE: Prenatal exposure to maternal infection is associated with an increased risk of epilepsy in childhood. The similarity of estimates across types of antibiotics suggests that processes common to all infections underlie this outcome, rather than specific pathogens or drugs. PMID- 22295116 TI - Genome-wide association study of copy number variants suggests LTBP1 and FGD4 are important for alcohol drinking. AB - Alcohol dependence (AD) is a complex disorder characterized by psychiatric and physiological dependence on alcohol. AD is reflected by regular alcohol drinking, which is highly inheritable. In this study, to identify susceptibility genes associated with alcohol drinking, we performed a genome-wide association study of copy number variants (CNVs) in 2,286 Caucasian subjects with Affymetrix SNP6.0 genotyping array. We replicated our findings in 1,627 Chinese subjects with the same genotyping array. We identified two CNVs, CNV207 (combined p-value 1.91E-03) and CNV1836 (combined p-value 3.05E-03) that were associated with alcohol drinking. CNV207 and CNV1836 are located at the downstream of genes LTBP1 (870 kb) and FGD4 (400 kb), respectively. LTBP1, by interacting TGFB1, may down regulate enzymes directly participating in alcohol metabolism. FGD4 plays a role in clustering and trafficking GABA(A) receptor and subsequently influence alcohol drinking through activating CDC42. Our results provide suggestive evidence that the newly identified CNV regions and relevant genes may contribute to the genetic mechanism of alcohol dependence. PMID- 22295117 TI - Activation of CD40 with platelet derived CD154 promotes reactive oxygen species dependent death of human hepatocytes during hypoxia and reoxygenation. AB - BACKGROUND: Hypoxia and hypoxia-reoxygenation (H-R) are pathogenic factors in many liver diseases that lead to hepatocyte death as a result of reactive oxygen species (ROS) accumulation. The tumor necrosis factor super-family member CD154 can also induce hepatocyte apoptosis via activation of its receptor CD40 and induction of autocrine/paracrine Fas Ligand/CD178 but the relationship between CD40 activation, ROS generation and apoptosis is poorly understood. We hypothesised that CD40 activation and ROS accumulation act synergistically to drive human hepatocyte apoptosis. METHODS: Human hepatocytes were isolated from liver tissue and exposed to an in vitro model of hypoxia and H-R in the presence or absence of CD154 and/or various inhibitors. Hepatocyte ROS production, apoptosis and necrosis were determined by labelling cells with 2',7' dichlorofluorescin, Annexin-V and 7-AAD respectively in a three-colour reporter flow cytometry assay. RESULTS: Exposure of human hepatocytes to recombinant CD154 or platelet-derived soluble CD154 augments ROS accumulation during H-R resulting in NADPH oxidase-dependent apoptosis and necrosis. The inhibition of c-Jun N terminal Kinase and p38 attenuated CD154-mediated apoptosis but not necrosis. CONCLUSIONS: CD154-mediated apoptosis of hepatocytes involves ROS generation that is amplified during hypoxia-reoxygenation. This finding provides a molecular mechanism to explain the role of platelets in hepatocyte death during ischemia reperfusion injury. PMID- 22295118 TI - Co-infection with the friend retrovirus and mouse scrapie does not alter prion disease pathogenesis in susceptible mice. AB - Prion diseases are fatal, transmissible neurodegenerative diseases of the central nervous system. An abnormally protease-resistant and insoluble form (PrP(Sc)) of the normally soluble protease-sensitive host prion protein (PrP(C)) is the major component of the infectious prion. During the course of prion disease, PrP(Sc) accumulates primarily in the lymphoreticular and central nervous systems. Recent studies have shown that co-infection of prion-infected fibroblast cells with the Moloney murine leukemia virus (Mo-MuLV) strongly enhanced the release and spread of scrapie infectivity in cell culture, suggesting that retroviral coinfection might significantly influence prion spread and disease incubation times in vivo. We now show that another retrovirus, the murine leukemia virus Friend (F-MuLV), also enhanced the release and spread of scrapie infectivity in cell culture. However, peripheral co-infection of mice with both Friend virus and the mouse scrapie strain 22L did not alter scrapie disease incubation times, the levels of PrP(Sc) in the brain or spleen, or the distribution of pathological lesions in the brain. Thus, retroviral co-infection does not necessarily alter prion disease pathogenesis in vivo, most likely because of different cell-specific sites of replication for scrapie and F-MuLV. PMID- 22295119 TI - Elevated pontine and putamenal GABA levels in mild-moderate Parkinson disease detected by 7 tesla proton MRS. AB - BACKGROUND: Parkinson disease (PD) is characterized by the degeneration of nigrostriatal dopaminergic neurons. However, postmortem evidence indicates that the pathology of lower brainstem regions, such as the pons and medulla, precedes nigral involvement. Consistently, pontomedullary damage was implicated by structural and PET imaging in early PD. Neurochemical correlates of this early pathological involvement in PD are unknown. METHODOLOGY/PRINCIPAL FINDING: To map biochemical alterations in the brains of individuals with mild-moderate PD we quantified neurochemical profiles of the pons, putamen and substantia nigra by 7 tesla (T) proton magnetic resonance spectroscopy. Thirteen individuals with idiopathic PD (Hoehn & Yahr stage 2) and 12 age- and gender-matched healthy volunteers participated in the study. gamma-Aminobutyric acid (GABA) concentrations in the pons and putamen were significantly higher in patients (N = 11, off medications) than controls (N = 11, p<0.001 for pons and p<0.05 for putamen). The GABA elevation was more pronounced in the pons (64%) than in the putamen (32%). No other neurochemical differences were observed between patients and controls. CONCLUSION/SIGNIFICANCE: The GABA elevation in the putamen is consistent with prior postmortem findings in patients with PD, as well as with in vivo observations in a rodent model of PD, while the GABA finding in the pons is novel. The more significant GABA elevation in the pons relative to the putamen is consistent with earlier pathological involvement of the lower brainstem. This study provides in vivo evidence for an alteration in the GABAergic tone in the lower brainstem and striatum in early-moderate PD, which may underlie disease pathogenesis and may provide a biomarker for disease staging. PMID- 22295120 TI - High resolution in vivo bioluminescent imaging for the study of bacterial tumour targeting. AB - The ability to track microbes in real time in vivo is of enormous value for preclinical investigations in infectious disease or gene therapy research. Bacteria present an attractive class of vector for cancer therapy, possessing a natural ability to grow preferentially within tumours following systemic administration. Bioluminescent Imaging (BLI) represents a powerful tool for use with bacteria engineered to express reporter genes such as lux. BLI is traditionally used as a 2D modality resulting in images that are limited in their ability to anatomically locate cell populations. Use of 3D diffuse optical tomography can localize the signals but still need to be combined with an anatomical imaging modality like micro-Computed Tomography (MUCT) for interpretation.In this study, the non-pathogenic commensal bacteria E. coli K-12 MG1655 and Bifidobacterium breve UCC2003, or Salmonella Typhimurium SL7207 each expressing the luxABCDE operon were intravenously (i.v.) administered to mice bearing subcutaneous (s.c) FLuc-expressing xenograft tumours. Bacterial lux signal was detected specifically in tumours of mice post i.v.-administration and bioluminescence correlated with the numbers of bacteria recovered from tissue. Through whole body imaging for both lux and FLuc, bacteria and tumour cells were co-localised. 3D BLI and MUCT image analysis revealed a pattern of multiple clusters of bacteria within tumours. Investigation of spatial resolution of 3D optical imaging was supported by ex vivo histological analyses. In vivo imaging of orally-administered commensal bacteria in the gastrointestinal tract (GIT) was also achieved using 3D BLI. This study demonstrates for the first time the potential to simultaneously image multiple BLI reporter genes three dimensionally in vivo using approaches that provide unique information on spatial locations. PMID- 22295121 TI - Role of AMP-activated protein kinase on steroid hormone biosynthesis in adrenal NCI-H295R cells. AB - Regulation of human androgen biosynthesis is poorly understood. However, detailed knowledge is needed to eventually solve disorders with androgen dysbalance. We showed that starvation growth conditions shift steroidogenesis of human adrenal NCI-H295R cells towards androgen production attributable to decreased HSD3B2 expression and activity and increased CYP17A1 phosphorylation and 17,20-lyase activity. Generally, starvation induces stress and energy deprivation that need to be counteracted to maintain proper cell functions. AMP-activated protein kinase (AMPK) is a master energy sensor that regulates cellular energy balance. AMPK regulates steroidogenesis in the gonad. Therefore, we investigated whether AMPK is also a regulator of adrenal steroidogenesis. We hypothesized that starvation uses AMPK signaling to enhance androgen production in NCI-H295R cells. We found that AMPK subunits are expressed in NCI-H295 cells, normal adrenal tissue and human as well as pig ovary cells. Starvation growth conditions decreased phosphorylation, but not activity of AMPK in NCI-H295 cells. In contrast, the AMPK activator 5-aminoimidazole-4-carboxamide (AICAR) increased AMPKalpha phosphorylation and increased CYP17A1-17,20 lyase activity. Compound C (an AMPK inhibitor), directly inhibited CYP17A1 activities and can therefore not be used for AMPK signaling studies in steroidogenesis. HSD3B2 activity was neither altered by AICAR nor compound C. Starvation did not affect mitochondrial respiratory chain function in NCI-H295R cells suggesting that there is no indirect energy effect on AMPK through this avenue. In summary, starvation mediated increase of androgen production in NCI-H295 cells does not seem to be mediated by AMPK signaling. But AMPK activation can enhance androgen production through a specific increase in CYP17A1-17,20 lyase activity. PMID- 22295122 TI - Association of sleep duration with chronic diseases in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study. AB - BACKGROUND: In view of the reduced number of hours devoted to sleep in modern western societies the question arises what effects might result from sleep duration on occurrence of chronic diseases. METHODS: Data from 23 620 middle-aged participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, that were recruited between 1994-1998, were analyzed by using Cox proportional hazard regression to examine the association between self reported sleep duration at baseline and incidence of chronic diseases, such as diabetes, myocardial infarction, stroke, and cancer. RESULTS: During a mean follow-up period of 7.8 years 841 incident cases of type 2 diabetes, 197 cases of myocardial infarction, 169 incident strokes, and 846 tumor cases were observed. Compared to persons sleeping 7-<8 h/day, participants with sleep duration of <6 h had a significantly increased risk of stroke (Hazard Ratio (HR) = 2.06, 95% confidence interval (CI): 1.18-3.59), cancer (HR = 1.43, 95% CI: 1.09-1.87), and overall chronic diseases (HR = 1.31, 95% CI: 1.10-1.55) in multivariable adjusted models. Self-reported daytime sleep at baseline was not associated with incident chronic diseases in the overall study sample. However, there had been an effect modification of daytime sleep by hypertension showing that daytime sleep was inversely related to chronic disease risk among non-hypertensive participants but directly related to chronic diseases among hypertensives. CONCLUSION: Sleep duration of less than 6 h is a risky behavior for the development of chronic diseases, particularly stroke and cancer, and should be therefore addressed in public health campaigns. PMID- 22295123 TI - A plasma survey using 38 PfEMP1 domains reveals frequent recognition of the Plasmodium falciparum antigen VAR2CSA among young Tanzanian children. AB - PfEMP1 proteins comprise a family of variant antigens that appear on the surface of P. falciparum-infected erythrocytes and bind to multiple host receptors. Using a mammalian expression system and BioPlex technology, we developed an array of 24 protein constructs representing 38 PfEMP1 domains for high throughput analyses of receptor binding as well as total and functional antibody responses. We analyzed the reactivity of 561 plasma samples from 378 young Tanzanian children followed up to maximum 192 weeks of life in a longitudinal birth cohort. Surprisingly, reactivity to the DBL5 domain of VAR2CSA, a pregnancy malaria vaccine candidate, was most common, and the prevalence of reactivity was stable throughout early childhood. Reactivity to all other PfEMP1 constructs increased with age. Antibodies to the DBL2betaC2(PF11_0521) domain, measured as plasma reactivity or plasma inhibition of ICAM1 binding, predicted reduced risk of hospitalization for severe or moderately severe malaria. These data suggest a role for VAR2CSA in childhood malaria and implicate DBL2betaC2(PF11_0521) in protective immunity. PMID- 22295124 TI - ELR510444 inhibits tumor growth and angiogenesis by abrogating HIF activity and disrupting microtubules in renal cell carcinoma. AB - BACKGROUND: Hypoxia-inducible factor (HIF) is an attractive therapeutic target for renal cell carcinoma (RCC) as its high expression due to the loss of von Hippel-Lindau (VHL) promotes RCC progression. Considering this, we hypothesized that ELR510444, a novel orally available small molecule inhibitor of HIF activity, would reduce angiogenesis and possess significant activity in RCC. The mechanism of action and therapeutic efficacy of ELR510444 were investigated in in vitro and in vivo models of RCC. PRINCIPAL FINDINGS: ELR510444 decreased HIF 1alpha and HIF-2alpha levels, reduced RCC cell viability and clonogenic survival, and induced apoptosis. VHL-deficient RCC cells were more sensitive to ELR510444 mediated apoptosis and restoration of VHL promoted drug resistance. Higher concentrations of ELR51044 promoted apoptosis independently of VHL status, possibly due to the microtubule destabilizing properties of this agent. ELR510444 significantly reduced tumor burden in the 786-O and A498 RCC xenograft models. These effects were associated with increased necrosis and apoptosis and inhibition of angiogenesis. CONCLUSIONS: ELR510444 is a promising new HIF inhibitor that reduced RCC cell viability, induced apoptosis, and diminished tumor burden in RCC xenograft models. ELR510444 also destabilized microtubules suggesting that it possesses vascular disrupting and anti-angiogenic properties. Further investigation of ELR510444 for the therapy of RCC is warranted. PMID- 22295125 TI - Eighth Annual ISGIO Meeting Sets a New Benchmark. PMID- 22295126 TI - Chemotherapy outcomes for the treatment of unresectable intrahepatic and hilar cholangiocarcinoma: a retrospective analysis. AB - BACKGROUND: Recent clinical trials for "biliary cancers" include a heterogenous group of patients with cholangiocarcinoma, gallbladder, and ampullary cancers. Limited data exist regarding the relative effectiveness of known chemotherapeutic regimens specifically in intrahepatic or hilar cholangiocarcinoma. METHODS: Records of M D Anderson Cancer Center patients with unresectable intrahepatic and hilar cholangiocarcinoma who received first-line chemotherapy from January 1, 2005, to October 31, 2009, were retrospectively reviewed. The primary objective of this research was to determine overall tumor control rates with chemotherapeutic regimens used for first-line treatment of unresectable intrahepatic and hilar cholangiocarcinoma. Secondary objectives included duration of response, overall survival, and prognostic factors. RESULTS: Eighty-five patients met inclusion criteria and were eligible for analysis. The most commonly used regimen was gemcitabine/cisplatin (62%), followed by oxaliplatin and capecitabine (16%). There was no significant difference between tumor control rates with gemcitabine/cisplatin (72% PR + SD) and other regimens (69% PR + SD). There was no significant difference between overall survival with the use of gemcitabine/cisplatin (15.2 months) or alternative regimens (13.9 months). A decrease in overall survival was seen with elevated baseline CA 19-9 (p < .0001), an initial diagnosis of unknown primary tumor (p = .0001), and prior treatment with chemoradiation (p = .0018). CONCLUSION: In this retrospective review, both gemcitabine/cisplatin and alternative doublets (including capecitabine/oxaliplatin, gemcitabine/capecitabine, and gemcitabine/oxaliplatin) were effective regimens in maintaining disease control in intrahepatic and hilar cholangiocarcinoma. PMID- 22295127 TI - Association between dietary fiber and incident cases of colon polyps: the adventist health study. AB - BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer death in the United States. Most cases of CRC arise in adenomatous polyps. It has been estimated that 25%-35% of colon adenoma risk could be avoidable by modification of dietary and life-style habits. METHODS: We estimated the association between total dietary fiber and fiber intake from fruits, vegetables, and grains, and the risk of physician-diagnosed colon polyps among 2818 men and women who had undergone colonoscopy. Data were drawn from 2 cohort studies-the Adventist Health Study-1 (AHS-1) of 1976 and the Adventist Health Study-2 (AHS-2) conducted from 2002 to 2005. Dietary information was obtained from the self-administered questionnaire from AHS-1, while outcome was assessed from AHS-2 data. Multivariate logistic regression analysis was used to estimate the period risk of incident cases of polyps. RESULTS: A total of 441 incident cases of colon polyps were identified. After adjusting for age, sex, body mass index, physical activity, education, and alcohol and meat consumption, total fiber intake was inversely associated with the risk of colon polyps (odds ratio [OR] for highest vs lowest quartile = 0.71, 95% confidence interval [CI] 0.51-0.99). This association showed a dose-response effect (p = .04). Analyses of various sources of fiber showed the most clear effect of fiber from vegetables including legumes (OR for highest vs lowest quartile = 0.65; 95% CI 0.47-0.90; p = .02). CONCLUSIONS: In this population comprising a high proportion of vegetarians, persons who consumed low amounts of fiber, especially fiber contained in vegetables, had a higher risk of developing colon polyps. PMID- 22295128 TI - Prognostic factors for metastatic colorectal cancer patients undergoing irinotecan-based second-line chemotherapy. AB - BACKGROUND: No reports about factors that predict prognosis after second-line chemotherapy for metastatic colorectal cancer have been published. METHODS: We retrospectively analyzed 124 patients with metastatic colorectal cancer who received irinotecan-based second-line chemotherapy after first-line folinic acid/5-fluorouracil (5-FU)/oxaliplatin (FOLFOX) with or without bevacizumab. RESULTS: A multivariate Cox model revealed 5 prognostic factors for worse survival: ECOG performance status 2, pathologically poorly differentiated adenocarcinoma, peritoneal metastasis, progression-free survival of first-line FOLFOX < 6 months, and lactate dehydrogenase >= 400 IU/L. When patients were categorized into 3 risk groups-patients without any prognostic factors (low-risk, n = 55), patients with one prognostic factor (intermediate-risk, n = 32), and patients with 2 or more prognostic factors (high-risk, n = 37)-overall survival from initiation of second-line chemotherapy was 23.5, 14.6, and 5.5 months, respectively. The proportion of patients who were eligible to receive further chemotherapy after disease progression was significantly lower in the high-risk group (41%) than in the intermediate- (67%) and low-risk (95%) groups. CONCLUSION: Several prognostic factors for survival after second-line therapy and probability of receiving third-line chemotherapy were identified. This risk classification system might be useful for determining which patients should receive cetuximab in the second-line setting rather than the third-line setting. PMID- 22295129 TI - Factors influencing progression-free survival in gastrointestinal stromal tumors with special reference to pathologic features, cytogenetics, and radiologic response. AB - BACKGROUND: Treatment of gastrointestinal stromal tumors (GISTs) changed significantly with the advent of targeted therapy with imatinib. Clear markers predictive of response to imatinib therapy and disease-free survival in patients with GIST have not been identified. Even RECIST criteria are inadequate for predicting response to therapy, especially in patients with stable disease. Data collected at a tertiary care cancer center from 2003 to 2005 in south India were analyzed retrospectively to assess clinical, pathologic, and cytogenetic profiles of patients with GIST. In addition, radiologic responses to therapy were evaluated for correlation with the disease-free survival. METHODS: GIST was defined as a mesenchymal spindle/epitheloid cell lesion arising in the GI tract with CD117 positivity. Only data from patients with locally advanced or metastatic disease were analyzed. Clinical and pathologic details of the patients were noted from case records. NCCN guidelines were followed for the treatment. Radiologic response to therapy was reassessed according to RECIST, and progression-free survival calculated for all analyzed patients using intent-to treat analysis. RESULTS: The mean age of presentation was 42.8 +/- 5.3 years (24 60), with a male-to-female ratio of 1.5:1. Small intestine was the most common disease site (60%), followed by stomach (20%), mesentery (7.2%), colorectal regions (7.2%), and other sites (5.6%). The most frequent pathologic finding in patients having recurrence was high mitotic rate. Initial tumor size (either in the metastatic setting or in local recurrence) had no bearing on progression-free or overall survival, nor did initial anatomic location or site of metastasis. Histologically, however, patients with a mixed-cell morphology had shorter survival compared to the other morphologies. Those patients having any cytogenetic abnormality had worse outcome compared to those with normal karyotype. Similarly, among patients who achieved remission, those who did so within 12 weeks had better overall survival than did those with a delayed time to remission. Overall survival of patients having stable disease and late partial responses (after 3 months) was similar and superior to survival for patients whose disease progressed while on therapy. CONCLUSION: GISTs characterized by a high mitotic rate and mixed-cell morphology and any cytogenetic abnormalities are associated with poorer outcome. Similarly, shorter time to response was more important than the actual response to therapy. Initial disease site, the site of metastasis, and tumor size had no bearing on outcomes to therapy. PMID- 22295130 TI - Improving outcomes in cholangiocarcinomas. PMID- 22295131 TI - Hepatocellular carcinoma following renal transplantation. PMID- 22295132 TI - Crohn's disease diagnosis following discovery of in situ follicular lymphoma. PMID- 22295133 TI - Lynch Syndrome Associated With PMS2 Mutation: Understanding Current Concepts. PMID- 22295134 TI - Selective internal radiotherapy in metastatic esophageal adenocarcinoma. PMID- 22295135 TI - Metastasis from pancreatic cancer located at the incision line of a mastectomy: a case report and review of literature. PMID- 22295137 TI - Rationing care: stifling progress while increasing cost of cancer care. PMID- 22295136 TI - Translational research in gastrointestinal oncology: a focus on signaling pathways in pancreas cancer. PMID- 22295138 TI - We Can't Fight the Battle Without Ammunition. PMID- 22295140 TI - Gastrointestinal cancer research official journal of the international society of gastrointestinal oncology contents of volume 4, issues 1-6 january-december 2011. PMID- 22295139 TI - Upcoming articles. PMID- 22295141 TI - Transgenic overexpression of keratinocyte-specific VEGF and Ang1 in combination promotes wound healing under nondiabetic but not diabetic conditions. AB - VEGF and Angiopoietin (Ang)1 are growth factors that independently improve wound healing outcomes. Using a tet-repressible mouse model coupled with streptozotocin induced diabetes, we examined wound healing in diabetic and nondiabetic mice engineered to overexpress keratinocyte-specific (K5) VEGF, Ang1 or Ang1-VEGF combined. All nondiabetic mice healed more rapidly than their diabetic counterparts; however overexpression of VEGF, Ang1 or the combination failed to improve wound closure under diabetic conditions. Conversely, under nondiabetic conditions, combining Ang1 and VEGF resulted in rapid wound closure. Molecular analyses of diabetic and nondiabetic K5-Ang1-VEGF skin revealed no differences in VEGF expression but an 80% decrease in Ang1 under diabetic conditions, suggesting an integral role for Ang1. Nondiabetic K5-Ang1 mice healed more quickly and had significant increases in granulation tissue and a 60% decrease in re epithelialization 7 days after wounding. Furthermore, Ang1 stimulated primary mouse keratinocytes showed significantly less migration into a wound bed in an in vitro wound healing bioassay and had decreased pMAPK, pNFkappaB, pAkt, and pStat3 signaling. These data suggest that combined Ang1-VEGF overexpression cannot overcome diabetes-induced delays in wound healing but is efficacious under nondiabetic conditions possibly via Ang1-mediated delays in re-epithelialization and enhancement of granulation tissue formation, thereby allowing more rapid secondary intention healing. PMID- 22295142 TI - Impact of serosal involvement/extramural growth on the risk of synchronous and metachronous peritoneal spread in gastrointestinal stromal tumors: proposal for a macroscopic classification of GIST. AB - BACKGROUND: Peritoneal and hepatic metastases are the main routes of spread of gastrointestinal stromal tumors (GIST). However, criteria to predict the site and pattern of recurrence in individual cases are still lacking. PATIENTS: We retrospectively analyzed 67 consecutive GISTs with complete gross descriptions to correlate macroscopic patterns with clinical course. Primary endpoint was the appearance of synchronous or metachronous peritoneal disease. Tumors were classified into type I (luminal/intramural) and type II (extramural) based on the macroscopic/histologic presence or absence of normal tissue between deeper tumor border and serosa, respectively. RESULTS: Patients were 35 men and 32 women (mean age, 64 yrs) with gastric (n=32), small bowel (n=30) and large bowel (n=5) GISTs. Based on the above proposal, 22 tumors were classified as type I and 45 as type II. Type I tumors were predominantly gastric (18/22; P<0.001) and frequently had very low/low risk (14/22; P<0.001) whereas type II tumors were predominantly intestinal (31/45; P<0.001) and often of intermediate/high risk (36/45; P<0.001). Ten patients had synchronous peritoneal spread and 6/30 patients with a mean follow-up of 29 months developed metachronous peritoneal spread at a mean of 27 months. Tumor rupture was seen in 2 patients (3%). Thus, 16/40 patients (40%) had synchronous or metachronous peritoneal progression. Taken by gross type, peritoneal progression was seen in 15/30 type II compared to 1/10 type I tumors (p=0.032). CONCLUSION: this study points to extramural growth as a predictor of peritoneal recurrence in GIST, probably as a consequence of tumor rupture or due to microscopic serosal penetration. This study aimed at alerting surgical pathologists to the importance of careful gross and microscopic assessment of resection specimen harboring GIST to allow for reliable prospective evaluation of serosal involvement as an adverse prognostic factor in GIST. PMID- 22295143 TI - c-Ret-mediated hearing losses. AB - About 120 million people worldwide suffer from congenital (early-onset) hearing loss. Thirty percent of them have syndromic hearing loss and the remaining 70% have non-syndromic hearing loss. In addition, a large number of elderly people worldwide suffer from age-related (late-onset) hearing loss. c-Ret and c-RET have been shown to be essential for the development and maintenance of neurons including the enteric nervous system (ENS) in mice and humans. Impairments of endothelin receptor B (EDNRB) and SOX10 have been shown to cause a significantly increased risk of dominant sensorineural deafness in Hirschsprung disease (HSCR) patients. We have recently shown that impairments of tyrosine 1062 (Y1062) phosphorylation in c-Ret causes syndromic congenital deafness in mice and humans and non-syndromic age-related hearing loss with neurodegeneration of spiral ganglion neurons (SGNs) in mice. This review focuses on the pathogenesis of hearing loss caused by impairments of c-Ret. PMID- 22295144 TI - Protective effect of xanthohumol on toxin-induced liver inflammation and fibrosis. AB - Xanthohumol, the major prenylated chalcone found in hops, is known for its anti inflammatory properties. We have recently shown that xanthohumol inhibits hepatic inflammation and fibrosis in a murine model of nonalcoholic steatohepatitis. The aim of this study was to investigate the effect of xanthohumol in an acute model of liver injury. Carbon tetrachloride (CCl(4)), an industrial solvent, is a hepatotoxic agent and its administration is widely used as an animal model of toxin-induced liver injury. Xanthohumol was applied orally at a dose of 1 mg/g body weight 2 days prior as well as during and after exposure to CCl(4). 72 h after a single CCl(4) application histomorphology and serum levels of transaminases revealed considerable hepatocellular necrosis, which was accompanied by significantly enhanced hepatic expression of pro-inflammatory cytokines. Furthermore, elevated hepatic alpha-smooth muscle actin expression indicated activation of hepatic stellate cells, and in accordance, we detected enhanced hepatic expression levels of TGF-beta and collagen type I reflecting a marked fibrogenic response to CCl(4) exposure. While the degree of hepatocellular damage in response to CCl(4) was similar in mice which received xanthohumol and the control group, pro-inflammatory and profibrogenic hepatic gene expression were almost completely blunted in xanthohumol fed mice. Furthermore, xanthohumol fed mice revealed decreased hepatic NFkappaB activity. These results suggest that the protective effects of xanthohumol in this toxic liver injury model involves direct mechanisms related to its ability to block both hepatic inflammation and the activation of hepatic stellate cells, presumable at least in part via decreasing NFkappaB activity. Thus, this study further indicates the potential of xanthohumol application to prevent or ameliorate the development and progression of liver fibrosis in response to hepatic injury. PMID- 22295145 TI - An orthotopic model of platinum-sensitive high grade serous fallopian tube carcinoma. AB - Fallopian tube carcinoma (FTCA) is a very rare cancer type, but may be a useful platform for investigating high grade serous tumors of the pelvis that originate from a serous tubal intraepithelial carcinoma (STIC) precursor. Metastatic tumors from a patient diagnosed with Stage IIIC high grade serous FTCA (P0) were transplanted via intraperitoneal (IP) injection into a small cohort of mice (passage, P1). Patient information was obtained from the medical record. Tumors were grown, harvested and re-implanted or archived through P3. The P3 cohort was treated with saline (n=8) or cisplatin, 5 mg/kg (n=8), weekly for 4 weeks. After sacrifice, tumors from each passage and treatment group were passaged further, frozen or paraffin embedded. The patient underwent optimal cytoreductive surgery for Stage IIIC high grade serous FTCA in the presence of a STIC. The FTCA, areas of STIC and normal appearing FT stained positive for p53, PAX8, pH2AX and mib-1. The patient remained in remission 9 months after platinum-based chemotherapy. IP tumor propagation was readily achieved up to P3 in the mice. Similar to the patient, orthotopic tumors were identified along peritoneal and mesenteric surfaces. Tumor histopathological and molecular features were confirmed and maintained through P3. The P3 cisplatin-treated mice had fewer tumor implants, higher levels of pH2AX and lower levels of mib-1 expression compared to controls. This orthotopic model of platinum sensitive high grade serous FTCA is a viable platform to study the biology and treatment of FTCA and other STIC-related pelvic serous carcinomas. PMID- 22295146 TI - Pathologic observations of the duodenum in 615 consecutive duodenal specimens: I. benign lesions. AB - The author investigated histopathology of 615 consecutive duodenal specimens in our pathology laboratory. Computer search of the duodenal lesions was performed. Review of histological slides was done, when appropriate. The duodenal specimens were composed of 567 benign lesions and 48 malignant lesions. The 567 benign lesions were composed of chronic non-specific duodenitis in 334 cases (60.0%), duodenal ulcer in 101 cases (17,8%), heterotopic gastric mucosa in 81 cases (14.3%), hyperplastic polyp in 16 cases (2.8%), Brunner's gland hyperplasia in 14 cases (2.5%), Brunner's gland adenoma in 8 cases (1.4%), lymphoid polyp in 5 cases (0.8%), tubular adenoma in 4 cases (0.7%), lymphangioma in 2 cases (0.4%), endocrine nests in 1 case (0.2%), and amyloidosis in 1 case (0.2%). The chronic non-specific duodenitis was characterized by edema and lymphocytic infiltration. The duodenal ulcer was characterized by exudate, necrosis, granulation tissue and regenerative epithelium. The heterotopic gastric mucosa consisted of two types: one was composed of only foveolar epithelium (n=21) and another foveolar epithelium and fundic glands (n=60). Hyperplastic polyp was characterized by proliferation of gastric foveolar-like epithelium. The Brunner's gland hyperplasia was characterized by hyperplastic proliferation of the gland. The Brunner gland adenoma was characterized by neoplastic proliferation of the gland. The lymphoid polyp was characterized by large lymph follicles with large germinal centers. The tubular adenoma was characterized by adenomatous proliferation of intestinal epithelium, similar to colon adenoma. The lymphangioma was characterized by submucosal cavernous proliferation of lymphatics. The endocrine cell nests were characterized by non-neoplasmic proliferation of neuroendocrine cells. The amyloidosis was characterized by deposition of amorphous materials positive with Congo-red stain. PMID- 22295147 TI - Pathologic observations of the duodenum in 615 consecutive duodenal specimens in a single Japanese hospital: II. malignant lesions. AB - The author investigated histopathology of 615 consecutive duodenal specimens in our pathology laboratory in Japan. A computer review of the duodenal specimens was done. In cases of malignancy, histological slides were reviewed. The duodenal specimens were composed of 567 benign lesions (92%) and 48 malignant lesions (8%). The 48 malignant lesions were composed of 20 cases (42%) of primary adenocarcinoma, 10 cases (21%) of primary adenocarcinoma of ampulla Vater, 4 cases (8%) of primary squamous cell carcinoma, 1 (2%) cases of primary spindle cell carcinoma, 4 (8%) cases of carcinoid tumors, 1 (2%) case of malignant lymphoma, and 8 cases (17%) of secondary carcinoma from the pancreatic carcinoma or bile duct carcinoma. The primary adenocarcinoma (n=20) was composed of well differentiated adenocarcinoma (n=9), papillary adenocarcinoma (n=1), moderately differentiated adenocarcinoma (n=6), and poorly differentiated adenocarcinoma (n=4). The primary adenocarcinoma of the ampulla of Vater (n=10) was composed of well differentiated adenocarcinoma (n=7) and moderately differentiated adenocarcinoma (n=3). The primary squamous cell carcinoma (n=4) showed proliferation of malignant squamous cells with keratinization and intercellular bridges. The spindle cell carcinoma (n=1) consisted of only malignant spindle cells immunohistochemistry positive for various cytokeratins and vimentin. The carcinoid tumor (n=4) was typical carcinoid and showed organoid, trabecular, and ribbon-like arrangements. The carcinoid tumor was immunohistochemically positive for neuroendocrine markers such as CD56, neuron-specific enolase and synaptophysin. The malignant lymphoma (n=1) was diffuse large B-cell lymphoma immunohistochemically positive for CD10, CD20, and CD79alpha. The secondary carcinoma (n=8) was adenocarcinoma invaded from the pancreatic adenocarcinoma (n=6) and extrahepatic bile duct adenocarcinoma (n=2). PMID- 22295148 TI - Idiopathic pulmonary fibrosis: immunohistochemical analysis provides fresh insights into lung tissue remodelling with implications for novel prognostic markers. AB - AIM: This study explored the cellular and biological interrelationships involved in Idiopathic Pulmonary Fibrosis (IPF) lung tissue remodelling using immunohistochemical analysis. METHODS AND RESULTS: IPF and control lung tissues were examined for localisation of Epithelial Mesenchymal Transition (EMT), proliferation and growth factor markers assessing their relationship to key histological aberrations. E-cadherin was expressed in IPF and control (Alveolar type II) ATII cells (>75%). In IPF, mean expression of N-cadherin was scanty (<10%): however 4 cases demonstrated augmented expression in ATII cells correlating to histological disease status (Pearson correlation score 0.557). Twist was expressed within fibroblastic foci but not in ATII cells. Transforming Growth Factor- beta (TGF-beta) protein expression was significantly increased in IPF ATII cells with variable expression within fibroblastic foci. Antigen Ki-67 was observed within hyperplastic ATII cells but not in cells overlying foci. Collagen I and alpha-smooth muscle actin (alpha-SMA) were strongly expressed within fibroblastic foci (>75%); cytoplasmic collagen I in ATII cells was present in 3 IPF cases. IPF ATII cells demonstrated variable Surfactant Protein-C (SP-C). CONCLUSIONS: The pathogenesis of IPF is complex and involves multiple factors, possibly including EMT. Histological analysis suggests TGF-beta-stimulated myofib rob lasts initiate a contractile response within established fibroblastic foci while proliferating ATII cells attempt to instigate alveolar epithelium repair. Marker expression (N-cadherin and Ki-67) correlation with histological disease activity (as reflected by fibroblastic foci extent) may emerge as future prognostic indicators for IPF. PMID- 22295149 TI - Primary central nervous system B cell lymphoma with features intermediate between diffuse large B cell lymphoma and Burkitt lymphoma. AB - B cell lymphoma with features intermediate between diffuse large B cell lymphoma and Burkitt lymphoma (DLBCL/BL) is a new lymphoma entity which is recognized in the current World Health Organization (WHO) classification (2008). We report a case of a primary central nervous system lymphoma (PCNSL) with findings consistent with DLBCL/BL. It is characterized by a very aggressive clinical course, and a widespread multifocal involvement of the CNS. Our case shows that a DLBCL/BL can manifest in the CNS alone without any systemic involvement. PMID- 22295150 TI - Clinicopathologic study of endometrial dedifferentiated endometrioid adenocarcinoma: a case report. AB - In 2006, dedifferentiated endometrioid adenocarcinoma (undifferentiated carcinoma associated with low-grade endometrioid carcinoma) of the uterus was first proposed. Dedifferentiated endometrioid carcinoma is part of the spectrum of undifferentiated carcinoma of the endometrium which is a highly aggressive tumor even when the undifferentiated component represents only 20% of the entire neoplasm. Therefore, accurate diagnosis and appropriate classification of this neoplasm are important in patient management. Lack of the recognition may lead to misclassification of dedifferentiated endometrioid adenocarcinoma as a pure endometrioid adenocarcinoma which is less aggressive. Only 4 papers have appeared in the literature so far on the topic of dedifferentiated endometrioid carcinoma. We report herein a first case of endometrial dedifferentiated endometrioid carcinoma in a 51-year old woman in Chinese population. We performed immunoperoxidase studies for 12 markers. Among them, cytokeratins, keratin 7, keratin 18, EMA, estrogen receptor (ER), progesterone receptor (PR), and vimentin show significantly differential expression between differentiated and undifferentiated area. PMID- 22295151 TI - Spindle cell carcinoma progressed from transitional cell carcinoma of the urinary bladder. AB - The author reports a very rare case of spindle cell carcinoma (SpCC) of the urinary bladder progressed from ordinary papillary transitional cell carcinoma (TCC). A 63-year-old man complained of hematuria. A transurethral endoscopic examination revealed a papillary tumor, and transuthetral resection of bladder tumor (TUR-BT) was performed and was diagnosed as ordinary papillary urothelial TCC. Since then, he was treated with TUR-BT eight times. Chemotherapy, radiation, radical cystectomy and lymph nodes dissection were performed 16 years after the first TUR-BT. However, he developed rectal mucosal metastasis. He is now alive 17 years after the first presentation. All the TUR-BT specimens were ordinary papillary TCCs without invasion (pTa). Immunohistochemically, the TUR-BT specimens were positive for pancytokeratin, high molecular weight cytokeratin (CK), CK 5/6, CK 7, CK 18, CK 19, CK 20, p53, p63, Ki-67 (10%), and negative for other antigens examined including vimentin. The cystectomy bladder specimens show broad ulcers and polypoid lesions, and malignant spindle cells (SpCC) invading into muscular layer were present. No TCC elements were recognized. The tumor cells were positive strongly for vimentin, and less strongly for pancytokeratin, high molecular weight cytokeratin, CK 5/6, CK 14, CK 18, p53, p63 and Ki-67 (95%), and negative for other antigens examined. The rectal metastatic lesion showed SpCC without TCC elements, and were strongly positive for vimentin, and weakly positive for pancytokeratin, S100 protein, p53, p63, Ki-67 (90%), neuron specific enolase, CD56, KIT and PDGFRA. It was negative for other antigen examined. It is strongly suggested that the present SpCC were progressed from ordinary TCC. PMID- 22295152 TI - Rare case of a primary non-dural central nervous system low grade B-cell lymphoma and literature review. AB - We present a case of a 70-year-old HIV negative man with a five-year history of progressive dysnomia and new onset right extremity numbness, dysarthria, and blurry vision. On magnetic resonance imaging (MRI), an infiltrative enhancing tumor was noted. Follow up brain biopsy results revealed a small lymphocytic infiltrate with scattered plasma cells in a predominantly perivascular growth pattern. Flow-cytometric findings revealed a lambda monotypic B-cell population. The morphology and the flow cytometric findings were consistent with involvement by a low grade B-cell lymphoma. Subsequent positron emission tomography (PET) studies along with bone marrow biopsy and serum protein electrophoresis showed no evidence of systemic disease. The above findings are consistent with involvement by a non-dural extranodal marginal zone B-cell lymphoma (MZBCL) primary to the central nervous system (CNS). This is the first reported case of a primary CNS MZBCL with flow cytometric analysis. A review of literature on this rare entity is also included. PMID- 22295153 TI - Malignant intraductal oncocytic papillary neoplasm of the common bile duct. AB - Recently, several cases of intraductal oncocytic papillary neoplasm (IOPN) of the liver and hepatic bile ducts have been reported. The author herein reports the first case of IOPN of the common bile duct (CBD). A 78-year-old man was admitted to our hospital because of jaundice. Imaging modalities including US, CT, MRI revealed an intraductal tumor of the middle CBD and biliary dilation distal to the tumor. A partial resection of the CBD was performed. Grossly, a papillary tumor measuring 20 * 15 mm was found within the CBD. Mucus is absent. Histologically, the papillary tumor was composed of atypical oncocytes. The atypia was enough to be diagnosed as adenocarcinoma. No invasive features were noted. Immunohistochemically, the tumor cells were positive for pancytokeratins (CK), CK 7, CK 18, CK19, EMA, CA19-9, CEA, mitochondria, p53 protein, C-erbB2, Ki 67 (labeling = 80%), MUC2, MUC5AC and MUC-6,. The tumor cells were negative for CK8, CK20, chromogranin, synaptophysin, neuron-specific enolase, S100 protein, CD56, MUC1, CD10 and CDX2. These immunohistochemical findings were compatible with IOPN. The patient died of other non-tumorous disease 7 year after the operation. In summary, the author presented the first case of IOPN of the CBD. PMID- 22295154 TI - Acquired hemophilia associated with bullous pemphigoid: a case report. AB - The development of factor VIII inhibitors in non-hemophilic patients is rare and may occur in healthy individuals, mostly elderly and women in postpartum period, and in patients with malignant neoplasia or autoimmune diseases, such as bullous pemphigoid. We described the case of a 60-year-old female patient who developed bullous pemphigoid for 3 month and presented with bleeding tendency and hematoma in the tongue. Therapy with methylprednisolone, cyclophosphamide, intravenous immunoglobulin and factor VIII reposition was instituted, resulting in a remission of the bleeding and negativity for antibodies against factor VIII titers. We concluded that, despite its rarity, the presence of acquired factor VIII inhibitors should be investigated when patients with autoimmune diseases develop bleeding manifestations. PMID- 22295155 TI - Lymphoepithelioma-like carcinoma of the colon. AB - An 85-year old female had a polypoid tumour in the sigmoid colon that histologically conformed to a lymphoepithelioma-like (LEL) carcinoma. The tumour was arranged in cords, chains, clusters and microalveoli of pleomorphic, irregular cells set within a dense intratumoral lymphocytic stroma. The tumour was EBV-negative and showed loss of MLH-1 and PMS-2 mismatch repair proteins. The patient did not fulfil the criteria for HNPCC. Only 5 other cases of primary colonic LEL carcinoma have been described previously and only one case appears to have an unequivocal association with EBV. In addition, one of the cases was encountered in a HNPCC patient. This is an unusual morphologic variant of a microsatellite unstable tumour with a LEL pattern, not associated with EBV. PMID- 22295156 TI - Aal izz well, old chaps! PMID- 22295157 TI - The Management of the 2009 pandemic Influenza A H1N1 virus infection. PMID- 22295158 TI - Some observations on the evolution and new improvement of Chinese guidelines for diagnosis and treatment of influenza. PMID- 22295159 TI - Treatment of influenza: Chinese medicine vs. western medicine. PMID- 22295160 TI - Rho kinases (ROCKs) in sepsis-induced acute lung injury. PMID- 22295161 TI - Involvement of the Rho kinases in mediating sepsis. PMID- 22295162 TI - Drug sensitivity testing for personalized lung cancer therapy. PMID- 22295163 TI - New studies address urgent need for early COPD diagnosis. PMID- 22295164 TI - Variables affecting survival after second primary lung cancer: A population-based study of 187 Hodgkin's lymphoma patients. AB - BACKGROUND: Patients successfully treated for Hodgkin's lymphoma (HL) are at known risk for subsequent malignancies, the most common of which is lung cancer. To date, no population-based study has analyzed prognostic variables for overall survival (OS) among HL survivors who developed non-small cell lung cancer (NSCLC). METHODS: For 187 HL patients who developed NSCLC (among 22,648 HL survivors), we examined the impact of the following variables on OS after NSCLC diagnosis: gender, race, sociodemographic status (based upon county of residence), calendar year and age at NSCLC diagnosis, NSCLC histology and grade, HL stage and subtype, radiation for HL and latency between HL and NSCLC. Patients were grouped by NSCLC stage as follows: localized, regional or distant. All patients were reported to the population-based Surveillance, Epidemiology, and End Results program. For those variables significant on univariate analyses, hazard ratios (HR) were derived from Cox proportional hazards model. RESULTS: Sociodemogaphic status, gender and latency between NSCLC and HL did not significantly affect OS of any NSCLC stage group. For patients with localized NSCLC, a history of mixed celluarlity HL was associated with a 3-fold improved OS (P=0.006). For patients with regional NSCLC, prior radiotherapy for HL was associated with a 2-fold worse OS (P=0.025). CONCLUSIONS: A history of mixed cellularity HL subtype and a history of no radiotherapy for HL are favorable prognostic factors among patients who develop NSCLC. Further research into clinicopathologic and treatment-associated variables potentially affecting OS after second primary NSCLC among HL survivors is warranted. PMID- 22295165 TI - Involvement of Rho kinase (ROCK) in sepsis-induced acute lung injury. AB - Indirect acute lung injury is associated with high morbidity and mortality. We investigated the link between Rho kinase (ROCK) activation and apoptotic cell death in sepsis induced acute lung injury. This hypothesis was tested by administering a specific, selective inhibitor of ROCK (Y-27632) to rats subjected to cecal ligation and puncture (CLP). Rats were randomly divided into 4 groups as; sham-operated, sham + Y-27632, CLP and CLP + Y-27632. Twenty-four hours later, each experiment was terminated and lungs analyzed. Histopathology was assessed by hematoxylin-eosin staining and the presence of apoptosis was evaluated through the TUNEL assay. Pulmonary activity of caspase 3 and ROCK 1 & 2 were measured by western blot. Interstitial edema, severely damaged pulmonary architecture with massive infiltration of the inflammatory cells and an increase in lung tissue TBARS levels as well as 3-NT to total tyrosine ratios were observed in untreated CLP animals. Pretreatment of animals with Y-27632, reduced lung injury in the CLP induced septic rats in each of these parameters of lung injury (p<0.05). Western immunoblot revealed active caspase cleavage and increased expression of active fragment of ROCK 1 & 2 in the CLP group. TUNEL assay showed an increase in percentage of apoptotic cells when comparing the CLP group with the CLP + Y-27632 group. These results suggest an important role of Rho kinase in sepsis induced lung injury by a mechanism that might be related to oxidative and/or nitrosative stress mediated caspase cleavage leading to apoptosis. PMID- 22295166 TI - Differences in chemosensitivity between primary and paired metastatic lung cancer tissues: In vitro analysis based on the collagen gel droplet embedded culture drug test (CD-DST). AB - BACKGROUND: To elucidate the differences in chemosensitivity to anticancer drugs between primary and metastatic lesions in non-small cell lung cancer (NSCLC) patients, we examined the in vitro chemosensitivities of surgically resected NSCLC tissues. METHODS: A total of 32 specimens were enrolled: 26 specimens of primary lesions paired with metastases in the lymph node, 3 specimens of primary lesions paired with metastases in the adrenal gland, and 3 specimens of primary lesions paired with metastases in the lung. The collagen gel droplet embedded culture drug test (CD-DST) was applied to examine the sensitivity of the tissues to anticancer drugs, including cisplatin, gemcitabine, vinorelbine, docetaxel and 5-fluorouracil. RESULTS: The degree of in vitro sensitivity to each anticancer drug varied between the primary and metastatic lesions. The sensitivity of the paired metastatic lesions was significantly lower than that of the primary lesions only for gemcitabine (P=0.029), vinorelbine (P=0.012), and docetaxel (P=0.009). The incidence of cases diagnosed as CD-DST-sensitive among the paired metastatic lesions was significantly lower than that for the primary lesions for vinorelbine (P=0.035) or docetaxel (P=0.022). The difference in the sensitivity to gemcitabine between the primary and paired non-lymphatic metastases was clearer than that between the primary lesion and paired lymph node metastases. CONCLUSIONS: The sensitivities of the paired metastatic lesions to some anticancer drugs were significantly lower than those of the primary lesions. When performing chemotherapy based on CD-DST data using primary tumors from patients with postoperative recurrence, an appropriate regimen can be selected by carefully considering these differences. PMID- 22295167 TI - An advanced stochastic model for mucociliary particle clearance in cystic fibrosis lungs. AB - BACKGROUND: A mathematical model describing mucociliary clearance in cystic fibrosis (CF) patients and its development with progressing course of the disease was developed. The approach should support the prediction of the disease state on the basis of measured bronchial clearance efficiencies. METHODS: The approach is based on the assumption of a steady-state steady-flow mucus transport through the tracheobronchial tree which enables the determination of airway generation specific mucus velocities by using a measured tracheal mucus velocity and a realistic morphometric dataset of the human lung. Architecture of the tracheobronchial tree was approximated by a stochastic model, reflecting the intra-subject variability of geometric parameters within a given lung generation. RESULTS: As predicted by the appropriately validated mathematical approach, mucociliary clearance efficiency in CF patients is partly significantly decreased with respect to healthy controls. 24-h retention of patients with mild CF (FEV(1) >70% of predicted) is reduced by 10% compared to healthy subjects, whilst 24-h retention of patients with moderate to severe CF (FEV(1) <70% of predicted) differs by 25% from that of the healthy controls. These discrepancies are further enhanced with continuation of the clearance process. CONCLUSIONS: The theoretical results lead to the conclusion that CF patients have a higher risk of inhaled particle accumulation and related particle overload in specific lung compartments than healthy subjects. PMID- 22295168 TI - A pilot study of nimotuzumab combined with cisplatin and 5-FU in patients with advanced esophageal squamous cell carcinoma. AB - OBJECTIVE: To observe the short-term effect and adverse reaction of Nimotuzumab in combination with chemotherapy on advanced esophageal squamous cell carcinoma (ESCC). METHOD: 19 patients were treated with the following protocol: Nimotuzumab 400mg/time/week in the 1(st) week, 200mg/time/week from the 2(nd) to 8(th) week, intravenous drip (IVD); Cisplatin 80 mg/m(2), IVD, 4 weeks a cycle and repeated again; 5-FU 750 mg/m(2), continuous 24-hours pump-in * 5 days, 4 weeks a cycle and repeated again. RESULT: 16 of all 19 patients can be evaluated. After treatment, RP is 42.1% (95% CI, 19.9-64.3%) and DCR is 68.4%; the main side effects include arrest of bone marrow, gastrointestinal reactions, asthenia, etc. CONCLUSION: Nimotuzumab in combination with cisplatin/5-FU regimens in patients with advanced ESCC is safe and effective, which deserves a further expanded sample research. PMID- 22295169 TI - Photodynamic therapy for the treatment of non-small cell lung cancer. AB - Photodynamic therapy is increasingly being utilized to treat thoracic malignancies. For patients with early-stage non-small cell lung cancer, photodynamic therapy is primarily employed as an endobronchial therapy to definitely treat endobronchial, roentgenographically occult, or synchronous primary carcinomas. As definitive monotherapy, photodynamic therapy is most effective in treating bronchoscopically visible lung cancers <=1 cm with no extracartilaginous invasion. For patients with advanced-stage non-small cell lung cancer, photodynamic therapy can be used to palliate obstructing endobronchial lesions, as a component of definitive multi-modality therapy, or to increase operability or reduce the extent of operation required. A review of the available medical literature detailing all published studies utilizing photodynamic therapy to treat at least 10 patients with non-small cell lung cancer is performed, and treatment recommendations and summaries for photodynamic therapy applications are described. PMID- 22295170 TI - Acute pulmonary embolism after pneumonectomy. AB - Pulmonary embolism (PE) by occlusion of the pulmonary arterial bed may lead to acute life-threatening but potentially reversible right ventricular failure, one of the most severe complications of thoracic surgery. Still, the incidence of acute pulmonary embolism after surgery is reduced by comprehensive anticoagulant prevention, improved surgical techniques, appropriate perioperative management and early ambulation. However, there is difficulty in diagnosing PE after thoracic surgery due to the lack of specific clinical manifestations. So that optimal diagnostic strategy and management according to the clinical presentation and estimated risk of an adverse outcome is fundamental. PMID- 22295171 TI - Psoas muscle metastases in non-small cell lung cancer. AB - Lung cancer is the leading cause of cancer-related death in the U.S. and often spreads via lymphatics or through hematogenous metastasis to the brain, bone and adrenal glands. Isolated metastases to skeletal muscle, including the psoas muscles, are very uncommon. The present report is a case series of three patients with psoas metastases from non-small cell lung cancer (NSCLC) and a review of the relevant literature. Three patients presented with psoas muscle metastases from NSCLC detected on diagnostic imaging. All patients were treated with radiotherapy to the psoas muscle, and two patients were treated with curative intent on an oligometastatic paradigm. Radiotherapy to the psoas muscle was effective and well tolerated. PMID- 22295172 TI - Chinese guidelines on the diagnosis and treatment of primary lung cancer (2011). PMID- 22295173 TI - Trichothecene mycotoxins inhibit mitochondrial translation--implication for the mechanism of toxicity. AB - Fusarium head blight (FHB) reduces crop yield and results in contamination of grains with trichothecene mycotoxins. We previously showed that mitochondria play a critical role in the toxicity of a type B trichothecene. Here, we investigated the direct effects of type A and type B trichothecenes on mitochondrial translation and membrane integrity in Saccharomyces cerevisiae. Sensitivity to trichothecenes increased when functional mitochondria were required for growth, and trichothecenes inhibited mitochondrial translation at concentrations, which did not inhibit total translation. In organello translation in isolated mitochondria was inhibited by type A and B trichothecenes, demonstrating that these toxins have a direct effect on mitochondrial translation. In intact yeast cells trichothecenes showed dose-dependent inhibition of mitochondrial membrane potential and reactive oxygen species, but only at doses higher than those affecting mitochondrial translation. These results demonstrate that inhibition of mitochondrial translation is a primary target of trichothecenes and is not secondary to the disruption of mitochondrial membranes. PMID- 22295174 TI - Pea Albumin 1 subunit b (PA1b), a promising bioinsecticide of plant origin. AB - PA1b (Pea Albumin 1, subunit b) is a peptide extract from pea seeds showing significant insecticidal activity against certain insects, such as cereal weevils (genus Sitophilus), the mosquitoes Culex pipiens and Aedes aegyptii, and certain species of aphids. PA1b has great potential for use on an industrial scale and for use in organic farming: it is extracted from a common plant; it is a peptide (and therefore suitable for transgenic applications); it can withstand many steps of extraction and purification without losing its activity; and it is present in a seed regularly consumed by humans and mammals without any known toxicity or allergenicity. The potential of this peptide to limit pest damage has stimulated research concerning its host range, its mechanism of action, its three dimensional structure, the natural diversity of PA1b and its structure-function relationships. PMID- 22295176 TI - Observation of T-2 toxin and HT-2 toxin glucosides from Fusarium sporotrichioides by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). AB - The trichothecenes produced by solid and liquid cultures of Fusarium sporotrichioides were evaluated with high performance liquid chromatography tandem mass spectrometry (LC-MS/MS). Along with the expected T-2 toxin HT-2 toxin and neosolaniol, two additional compounds were detected, which had ions 162 m/z higher than those in the mass spectra of T-2 toxin or HT-2 toxin. Fragmentation behavior of these two compounds was similar to that of T-2 toxin and HT-2 toxin. Based on LC-MS/MS behavior, it is proposed that the two compounds are T-2 toxin 3 O-glucoside and HT-2 toxin 3-O-glucoside. Production of the two glucosides was measured in kernels from wheat and oat inoculated with F. sporotrichiodes, as well as in cultures grown in liquid media and on cracked corn or rice. Production of glucosides in wheat and oats suggest that they may also be present in naturally contaminated cereals. PMID- 22295175 TI - Current and future experimental strategies for structural analysis of trichothecene mycotoxins--a prospectus. AB - Fungal toxins, such as those produced by members of the order Hypocreales, have widespread effects on cereal crops, resulting in yield losses and the potential for severe disease and mortality in humans and livestock. Among the most toxic are the trichothecenes. Trichothecenes have various detrimental effects on eukaryotic cells including an interference with protein production and the disruption of nucleic acid synthesis. However, these toxins can have a wide range of toxicity depending on the system. Major differences in the phytotoxicity and cytotoxicity of these mycotoxins are observed for individual members of the class, and variations in toxicity are observed among different species for each individual compound. Furthermore, while diverse toxicological effects are observed throughout the whole cellular system upon trichothecene exposure, the mechanism of toxicity is not well understood. In order to comprehend how these toxins interact with the cell, we must first have an advanced understanding of their structure and dynamics. The structural analysis of trichothecenes was a subject of major interest in the 1980s, and primarily focused on crystallographic and solution-state Nuclear Magnetic Resonance (NMR) spectroscopic studies. Recent advances in structural determination through solution- and solid-state NMR, as well as computation based molecular modeling is leading to a resurgent interest in the structure of these and other mycotoxins, with the focus shifting in the direction of structural dynamics. The purpose of this work is to first provide a brief overview of the structural data available on trichothecenes and a characterization of the methods commonly employed to obtain such information. A summary of the current understanding of the relationship between structure and known function of these compounds is also presented. Finally, a prospectus on the application of new emerging structural methods on these and other related systems is discussed. PMID- 22295177 TI - Phytotoxins produced by fungi associated with grapevine trunk diseases. AB - Up to 60 species of fungi in the Botryosphaeriaceae family, genera Cadophora, Cryptovalsa, Cylindrocarpon, Diatrype, Diatrypella, Eutypa, Eutypella, Fomitiporella, Fomitiporia, Inocutis, Phaeoacremonium and Phaeomoniella have been isolated from decline-affected grapevines all around the World. The main grapevine trunk diseases of mature vines are Eutypa dieback, the esca complex and cankers caused by the Botryospheriaceae, while in young vines the main diseases are Petri and black foot diseases. To understand the mechanism of these decline associated diseases and the symptoms associated with them, the toxins produced by the pathogens involved in these diseases were isolated and characterised chemically and biologically. So far the toxins of only a small number of these decline fungi have been studied. This paper presents an overview of the toxins produced by the most serious of these vine wood pathogens: Eutypa lata, Phaeomoniella chlamydospora, Phaeoacremonium aleophilum and some taxa in the Botryosphaeriaceae family, and examines how these toxins produce decline symptoms. The chemical structure of these metabolites and in some cases their vivotoxin nature are also discussed. PMID- 22295178 TI - Efficacy and Safety of Low-Dose Cyclosporine with Everolimus and Steroids in de novo Heart Transplant Patients: A Multicentre, Randomized Trial. AB - A six-month, multicenter, randomized, open-label study was undertaken to determine whether renal function is improved using reduced-exposure cyclosporine (CsA) versus standard-exposure CsA in 199 de novo heart transplant patients receiving everolimus and steroids +/- induction therapy. Mean C(2) levels were at the low end of the target range in standard-exposure patients (n = 100) and exceeded target range in reduced-exposure patients (n = 99) throughout the study. Mean serum creatinine at Month 6 (the primary endpoint) was 141.0 +/- 53.1 MUmol/L in standard-exposure patients versus 130.1 +/- 53.7 MUmol/L in reduced exposure patients (P = 0.093). The incidence of biopsy-proven acute rejection >=3A at Month 6 was 21.0% (21/100) in the standard-exposure group and 16.2% (16/99) in the reduced-exposure group (n.s.). Adverse events and infections were similar between treatment groups. Thus, everolimus with reduced-exposure CsA resulted in comparable efficacy compared to standard-exposure CsA. No renal function benefits were demonstrated; that is possibly related to poor adherence to reduced CsA exposure. PMID- 22295179 TI - Characterization of DTI Indices in the Cervical, Thoracic, and Lumbar Spinal Cord in Healthy Humans. AB - The aim of this study was to characterize in vivo measurements of diffusion along the length of the entire healthy spinal cord and to compare DTI indices, including fractional anisotropy (FA) and mean diffusivity (MD), between cord regions. The objective is to determine whether or not there are significant differences in DTI indices along the cord that must be considered for future applications of characterizing the effects of injury or disease. A cardiac gated, single-shot EPI sequence was used to acquire diffusion-weighted images of the cervical, thoracic, and lumbar regions of the spinal cord in nine neurologically intact subjects (19 to 22 years). For each cord section, FA versus MD values were plotted, and a k-means clustering method was applied to partition the data according to tissue properties. FA and MD values from both white matter (average FA = 0.69, average MD = 0.93 * 10(-3) mm(2)/s) and grey matter (average FA = 0.44, average MD = 1.8 * 10(-3) mm(2)/s) were relatively consistent along the length of the cord. PMID- 22295180 TI - Parental Concerns about the Health of Adolescents with Intellectual Disability: A Brief Report. AB - Background. Parents of adolescents with intellectual disability are concerned about the future health and well-being needs of their children. Method. Qualitative data was collected as part of a cross-sectional descriptive study and semi-structured interviews were conducted with 32 parents. The results were themed. Results. Most parents discussed areas of their children's health which made them anxious about the future. These concerns were collated into five themes. Conclusion. The health and well-being themes were dependency, general health, challenging behaviours, and increasing support needs. PMID- 22295181 TI - Effects of secondhand smoke exposure on the health and development of african american premature infants. AB - Objective. To explore the effects of secondhand smoke exposure on growth, health related illness, and child development in rural African American premature infants through 24 months corrected age. Method. 171 premature infants (72 boys, 99 girls) of African American mothers with a mean birthweight of 1114 grams. Mothers reported on household smoking and infant health at 2, 6, 12, 18, and 24 months corrected age. Infant growth was measured at 6, 12, 18, and 24 months, and developmental assessments were conducted at 12 and 24 months. Results. Thirty percent of infants were exposed to secondhand smoke within their first 2 years of life. Secondhand smoke exposure was associated with poorer growth of head circumference and the development of otitis media at 2 months corrected age. Height, weight, wheezing, and child development were not related to secondhand smoke exposure. Conclusion. Exposure to secondhand smoke may negatively impact health of rural African American premature infants. Interventions targeted at reducing exposure could potentially improve infant outcomes. PMID- 22295182 TI - Folic Acid Supplementation for Women of Childbearing Age versus Supplementation for the General Population: A Review of the Known Advantages and Risks. AB - This paper focuses on the current best-evidence-based clinical practices and controversies surrounding folic acid supplementation/fortification for the prevention of neural tube defects (NTDs) during early pregnancy. The paper also discusses the controversies surrounding the effect of folic acid on the prevention as well as the promotion of cancer. Sufficient data is available to safely conclude that folic acid reduces the risk of NTDs during pregnancy; however, a safe dosage has not yet been calculated for the rest of the population. More research is necessary to study the complete role of folic acid in human growth and development. PMID- 22295183 TI - Health and functional status of adults with intellectual disability referred to the specialist health care setting: a five-year experience. AB - Aims and Method. The Developmental Disability Database in the Department of Rehabilitation Medicine at a metropolitan hospital was audited for observations on adults with Intellectual Disability living in the local region (total population 180,000) who were seen in an identified multidisciplinary specialist clinic, during 2006-2010. Results. There were 162 people (representing half the known number of adults with Intellectual Disability living in the region): 77 females, 85 males, age range 16-86 years. The most common complex disabilities referred to the specialists in this clinic were epilepsy (52%), challenging or changing behavior (42%) and movement disorders (34%). Early onset dementia was a feature of the group (7%). The prevalence of prescription of medications for gastro-oesophageal reflux was high (36%) and similar to the numbers of people taking psychotropic medications. The rates of chronic cardiovascular disease (2%), chronic respiratory disease (10%) and generalised arthritis (11%) were low overall, but did rise with increasing age. Conclusions. Complex neurological disabilities are common, and chronic medical illnesses are uncommon in adults with Intellectual Disability referred to specialist clinicians in this region. A combined, coordinated, multidisciplinary clinic model addresses some of the barriers experienced by adults with Intellectual Disability in the secondary health system. PMID- 22295184 TI - Prevalence of Depression and Dementia among Adults with Developmental Disabilities in Manitoba, Canada. AB - Study Objective. To estimate and compare the prevalence of dementia and depression among adults with and without developmental disabilities (DDs). Methods. We linked data from several provincial administrative databases to identify persons with DDs. We matched cases with DD with persons without DD as to sex, age, and place of residence. We estimated the prevalence of dementia and depression and compared the two groups using the Generalized Estimating Equations (GEEs) technique. Results. The estimated prevalence of depression and dementia among younger adults (20-54) and older adults (50+) with DD was significantly higher than the estimated rates for the matched non-DD group (Depression: younger adults: RR = 2.96 (95% CI 2.59-3.39); older adults: RR = 2.65 (95% CI 1.84 3.81)), (Dementia: younger adults: RR = 4.01 (95% CI 2.72-5.92); older adults: RR = 4.80 (95% CI 2.48-9.31)). Conclusion. Significant disparities exist in mental health between persons with and without DDs. PMID- 22295185 TI - Developing a self-administered questionnaire as a guide to consultations with women treated for breast cancer. AB - Background. Health professionals, including general practitioners involved in followup of breast cancer patients, need to systematically assess opportunities to offer patients support with ongoing or new problems. Methods. A self administered needs assessment questionnaire was developed with reference to a multidisciplinary team. Short, evidence-based, readable questions were emphasized, and questions were tested for face validity. The questions flowed across three domains: physical, social, and psychological. Content validity and user friendliness were assessed. Results. A final set of 30 questions was rated as easy to read and comprehend (Flesch Reading Ease score 65.8 and Flesch-Kincaid Grade Level 6.9). When piloted with twenty-one patients the self-administered questionnaire detected 121 items of unmet need encompassing all three domains. Conclusions. This self-administered questionnaire has the potential to assist in the holistic assessment of breast cancer patient after treatment. The clinical value of the self-administered questionnaire will need to be further tested before it can be widely adopted. PMID- 22295186 TI - The Prevalence of Depression among Family Caregivers of Children with Intellectual Disability in a Rural Setting in Kenya. AB - Caregivers of children with intellectual disability have a great responsibility that may be stressful. The psychological well-being of the care giver may affect the quality of care given to children with intellectual disability. Objective. The objective of the study was to determine the risk of depression in caregivers of children with intellectual disability. Setting. The study was conducted at Gachie Catholic Parish, Archdiocese of Nairobi (Kenya). Design. Cross sectional, descriptive study. Method. The study was conducted among 114 caregivers registered at the Gachie Parish program (in Kenya) for the intellectual disabled children. A researcher-designed social demographic questionnaire and the Beck depression inventory were administered to those that met the inclusion criteria. Results. Seventy-nine percent (79%) of the caregivers were at risk of clinical depression. Conclusion. Majority of the caregivers of children with intellectual disability were at risk of developing clinical depression. PMID- 22295187 TI - A new era in mental health care in vanuatu. AB - Inequity in health-care delivery for those with mental illness is widespread throughout low- and middle-income countries. In the Pacific Island countries there are many barriers to addressing the growing mental health burden. In an effort to address this problem, the WHO is coordinating the Pacific Islands Mental Health Network involving 18 countries in the Pacific region with the financial support of New Zealand Aid (NZAid). JB and DP have developed and presented mental health training to health professionals, community leaders, and social service personnel in an environment in Vanuatu that is very different from that of their usual Australian-based general practices. They discuss evidence for their work, an outline of the programme, some difficulties working across different cultures, and the enthusiasm with which the training has been greeted. Vanuatu is now well on its way to addressing the inequity of access to mental health care with a culturally appropriate and self-sustaining mental health workforce. PMID- 22295188 TI - Emerging longitudinal trends in health indicators for rural residents participating in a diabetes and cardiovascular screening program in northern Alberta, Canada. AB - Background. Geographic isolation, poverty, and loss of culture/tradition contribute to "epidemic" rates of diabetes amongst indigenous Canadians. The Mobile Diabetes Screening Initiative travels to rural indigenous and other remote communities in Alberta to screen for diabetes and cardiovascular risk. We sought to examine risk factors longitudinally. Methods. Clinical and anthropometric measurements were undertaken for 809 adults (aged 20-91) between November 2003 and December 2009. For those who had more than one MDSi visit, trend estimates (actual changes) were calculated for body mass index (BMI), weight, waist circumference, hemoglobin A1c (A1c), total cholesterol, and blood pressure. Results. Among those without diabetes (N = 629), BMI and weight increased (P < .01) and blood pressure decreased (P < .05). For those with diabetes (N = 180), significant improvements (P < .05) were observed for all indicators except waist circumference. Conclusion. Improvements observed suggest that MDSi's model may effectively mediate some barriers and support subjects in managing their health. PMID- 22295189 TI - Parental perceptions of a manchester service for autistic spectrum disorders. AB - Background. User feedback is now an integral part of both clinical governance and service development, and it also provides a key route to engaging parents and children. Autistic spectrum disorders (ASDs) can impact on all members of a family, and close working between parents and professionals is essential. Aim. To explore parental satisfaction rates and identify areas in need of improvement. Method. A postal survey was completed by parents whose children had been diagnosed with an ASD in the past 18 months in a Manchester Child and Adolescent Mental Health Service. The National Autism Plan for Children was used as a gold standard. Results. Parents were particularly satisfied with the way team members dealt with them and their children during appointments. However, the standard of written information provided about the condition, diagnosis, and support available could be improved. The findings show the benefits of receiving a diagnosis in the recommended timeframe. Discussion. We discuss ways of effectively using scarce resources. PMID- 22295190 TI - Community-based mental health intervention for underprivileged women in rural India: an experiential report. AB - Objective. To share experiences from a project that integrates a mental health intervention within a developmental framework of microcredit activity for economically underprivileged women in rural India. Method. The mental health intervention had two components: group counseling and stress management. The former comprised of ventilation and reassurance and the latter strengthening of coping skills and a relaxation technique. Focus group discussions were used to understand women's perception of how microcredit economic activity and the mental health intervention had affected their lives. Results. Women in the mental health intervention group reported reduction in psychological distress and bodily aches and pains. Majority (86%) reported that the quality of their sleep had improved with regular practice of relaxation and that sharing their problems in the group had helped them to unburden. The social support extended by the members to each other, made them feel that they were not alone and could face any life situation. Conclusion. The study provided qualitative evidence that adding the mental health intervention to the ongoing economic activity had made a positive difference in the lives of the women. Addressing mental health concerns along with livelihood initiatives can help to enhance both economic and social capital in rural poor women. PMID- 22295191 TI - Barriers to health care for chinese in the Netherlands. AB - This study examines utilisation of the Dutch health care system by Chinese people in the Netherlands as well as their attitudes to the system, paying special attention to mental health. Information was gathered by semistructured interviews (n = 102). The main issues investigated are access, help-seeking behaviour, and quality of care. Results showed that most respondents used Dutch health care as their primary method of managing health problems. Inadequate knowledge about the system and lack of Dutch language proficiency impede access to care, in particular registration with a General Practitioner (GP). Users complained that the care given differed from what they expected. Results also showed that the major problems are to be found in the group coming from the Chinese-speaking region. Western concepts of mental health appear to be widely accepted by Chinese in the Netherlands. However, almost half of our respondents believed that traditional Chinese medicine or other methods can also help with mental health problems. The provision of relevant information in Chinese appears to be important for improving access. Better interpretation and translation services, especially for first-generation migrants from the Chinese-speaking region, are also required. PMID- 22295192 TI - Teleophthalmology: a model for eye care delivery in rural and underserved areas of India. AB - Objectives. To describe the application of teleophthalmology in rural and underserved areas of India. Study Design. This paper describes the major teleophthalmology projects in India and its benefits. Results. Teleophthalmology is the use of telecommunication for electronic transfer of health-related data from rural and underserved areas of India to specialities in urban cities. The MDRF/WDF Rural Diabetes Project has proved to be very beneficial for improvement of quality health care in Tamilnadu and can be replicated at the national level. This community outreach programme using telemedicine facilities has increased awareness of eye diseases, improved access to specialized health care, helped in local community empowerment, and provided employment opportunities. Early detection of sight threatening disorders by teleophthalmology and prompt treatment can help decrease visual impairment. Conclusion. Teleophthalmology can be a very effective model for improving eye care delivery system in rural and underserved areas of India. PMID- 22295193 TI - Cancer and anorexia nervosa in the adolescence: a family-based systemic intervention. AB - Objective. Anorexia nervosa is difficult to diagnose in cancer patients since weight loss, aversion for food, and eating disturbances are frequent in patients undergoing chemotherapy and radiotherapy. Nevertheless, efforts are mandatory to recognize and manage this condition which may occur also in cancer patients with a special regard to adolescents. Methods. Through the clinical history of Anna, a 15-year-old adolescent with advanced cancer, we describe the effectiveness of a family-based systemic intervention to manage anorexia nervosa occurring in concomitance to osteosarcoma. Results. Through a two-year psychotherapy period involving different techniques applied to the whole family such as family genogram, family collage, and sculpture of family time, Anna was relieved from her condition. Conclusions. Upon early diagnosis and appropriate treatment, anorexia nervosa can be effectively approached in adolescent cancer patients. The presence of a life-threatening medical condition such as cancer may provide motivation for a patient to control disordered eating behavior in the context of an appropriate family-based systemic intervention. The general frame of anorexia occurring in cancer-bearing adolescents is reviewed and discussed. PMID- 22295194 TI - The burden of caring for children with emotional or conduct disorders. AB - Introduction. There is a paucity of evidence from epidemiological studies on the burden of children's emotional and conduct disorders on their parents. The main purpose of this study is to describe the problems experienced by parents of children with conduct and emotional disorders using data from a large national study on the mental health of children and young people in Great Britain. Materials and Methods. The Development and Well-Being Assessment and sections of the Child and Adolescent Burden Assessment were included in a nationally representative survey of the mental health of 10,438 children, aged 5-15, in Great Britain. Results and Discussion. Approximately half the parents of children with conduct disorder reported that they felt restricted in doing things socially with or without their children, embarrassed about their child's problems, and that these also made the relationship with their partner more strained. Conclusions. There is a growing need for research on the consequences of children mental disorders on families to increase the awareness of frontline workers on the burden to parents. Because parents feel embarrassed and stigmatized, they may hide their own feelings which may further exacerbate the situation. PMID- 22295195 TI - Individual Physician versus Team-Based Medical Encounters: Maximizing the Efficiency of a Medical Relief Service in Rural Honduras. AB - Background. For several years, the Virginia Commonwealth University (VCU) Department of Internal Medicine has traveled to the towns of La Hicaca and Coyoles in rural Honduras. In 2010, a new encounter method was employed during the brigade in Coyoles. Objectives. To examine the differences in clinical encounters and adherence with chronic diseases and public health screening between the traditional and team-based encounter methods. Methods. Chi-square analysis was used to determine statistical significance between encounter methods over several variables used in the standard interview form. Results. 314 patients were interviewed using the team-based approach, and 153 patients were interviewed with the traditional model. Statistically significant increases in compliance using the team-based method were observed with diabetes screening and selecting candidacy for antihelminthic therapy. Other variables with significantly increased compliance using the team-based method were compliance with checking a blood glucose value, diagnosing GERD, and prescribing medication such as analgesics and multivitamins. Conclusion. Our results show a statistically significant increase in compliance with data collection and clinical screening using the new team-based encounter method. This design provides a more goal oriented approach to the patient interview. These data will help guide more effective delivery of health care on future medical relief trips to Honduras. PMID- 22295196 TI - Factors associated with physician assistant practice in rural and primary care in utah. AB - Physician Assistants (PAs) have become an integral part of the United States (U.S.) health care system since the profession began in the late 1960s. PAs have been suggested as solutions to predicted physician shortages especially in primary care. This study examined the predictors of primary care and rural practice patterns of PAs in Utah. A cross sectional survey design was utilized. The outcome variables were practice specialty and practice location. The predictor variables were age, gender, number of years in practice, location of upbringing, and professional school of graduation. There was a response rate of 67.7%. The Utah Division of Occupational and Professional Licensing (DOPL) provided the list of licensed PAs in the state. Physician assistants who reported being raised in rural communities were 2.29 times more likely to be practicing in rural communities (95% CI 0.89-5.85). Female PAs had lower odds of practicing in a rural area (OR: 0.26; 95% CI: 0.10-0.66). Female PAs had lower odds of practicing in primary care versus their male counterparts (OR: 0.56; 95% CI: 0.33 0.96). Graduation from the Utah PA Program was more likely to result in primary care practice (OR: 2.16; 95% CI: 1.34-3.49). PMID- 22295197 TI - Health promoting schools provide community-based learning opportunities conducive to careers in rural practice. AB - The World Health Organization conceived "health-promoting schools" as a means of providing the information and support systems necessary for the worldwide changes in behavior that are needed to improve health globally and decrease health care costs. We developed and evaluated a model of progressively implementing health promoting schools with support from university medical school trainees in Canada and Uganda. The model uses oral health as a medium for establishing rapport and success around a topic with little stigma. The evaluation involved questionnaires of the Canadian trainees about practice intentions before and after involvement in the health-promoting schools to determine whether community-based learning in health-promoting schools resulted in more trainees planning to work in rural areas or underserved countries. We found that Canadian medical trainees cited their personal involvement and perceived ability to effect significant and identifiable positive change in both the school children and the community as reasons why they were more willing to practice in rural or under-served areas. PMID- 22295198 TI - Spatial variation in general medical services income in dublin general practitioners. AB - The general medical services (GMS) scheme provides care free at the point of use for the 30% most economically deprived section of the population and the elderly. Almost all people of over-70-year olds are eligible for the GMS scheme potentially directing resources away from those most in need. The aim of this study is to analyse the relationship between practice GMS income and deprivation amongst Dublin-based general practitioners (GPs). The practice GMS income in Dublin was analysed in relation to practice characteristics including the number of GPs, catchment area population, proportion of over-70-year olds in the catchment area, catchment deprivation, number of GMS GPs within 2 km, and average GMS practice income within 2 km. Practice GMS income was highest in deprived areas but is also a valuable source of income in the least deprived areas. The capitation rate for over-70-year olds provides an incentive for GPs to locate in affluent areas and potentially directs resources away from those in greater need. PMID- 22295199 TI - Gendered perceptions of sexual behaviour in rural South Africa. AB - This paper discusses sexual behaviour findings collected through eleven homogenous focus group discussions conducted among women and men in a predominantly Zulu population in rural KwaZulu-Natal, South Africa. The objective of this paper is to shed light on sexual behaviour in a rural community. The findings suggest that sex is a taboo subject and the discussion around it is concealed in the use of polite language, euphemisms, and gestures. There are gender and generational dimensions to the discussion of sex. The contribution of this paper lies in the identification of what rural people discuss about sex and the influence of cultural practices and urban or global forces on sexual behaviour in rural areas. The paper adds to the growing body of literature on the use of focus groups in understanding sexual behaviour in rural contexts. PMID- 22295200 TI - To Drive or Not to Drive: Assessment Dilemmas for GPs. AB - Introduction. Most Australians are dependent on their cars for mobility, thus relinquishing driving licences for medical reasons poses challenges. Aims. To investigate how general practitioners (GPs) recognise and manage patients' fitness to drive, GPs' attitudes and beliefs about their role as assessors, and GPs' experiences in assessing and reporting to driving authorities and identify GPs' educational needs. Methods. Mixed methods: questionnaire mailed to GPs from three rural and two metropolitan Divisons of General Practice in Victoria, Australia. Results. 217/1028 completed questionnaires were returned: 85% recognised a patients' fitness to drive, 54% felt confident in their assessment ability, 21% felt the GP should have primary responsibility for declaring patients' fitness to drive, 79% felt that reporting a patient would negatively impact on the doctor-patient relationship, 74% expressed concern about legal liability, and 74% favoured further education. Discussion. This study provides considerable information including recommendations about GP education, the assessment forms, and legal clarification. PMID- 22295201 TI - Lipoplatin treatment in lung and breast cancer. AB - The introduction of cisplatin in cancer treatment represents an important achievement in the oncologic field. Many types of cancers are now treated with this drug, and in testicular cancer patients major results are reached. Since 1965, other compounds were disovered and among them carboplatin and oxaliplatin are the main Cisplatin analogues showing similar clinical efficacy with a safer toxicity profile. Lipoplatin is a new liposomal cisplatin formulation which seems to have these characteristics. Lipoplatin was shown to be effective in NSCLC both in phase 2 and phase 3 trials, with the same response rate of Cisplatin, a comparable overall survival but less toxicity. A new protocol aiming to elucidate the double capacity of Lipoplatin to act as a chemotherapeutic and angiogenetic agent in triple-negative breast cancer patients is upcoming. PMID- 22295202 TI - A regimen of taxol, Ifosfamide, and platinum for recurrent advanced squamous cell cancer of the anal canal. AB - The typically recommended chemotherapy options in metastatic anal cancer generally yield partial remissions with limited benefit for the majority of patients. TIP is a regimen containing paclitaxel (Taxol), ifosfamide, and cisplatin that is known to have significant activity in patients with squamous cell cancers of the head and neck as well as in cervical cancer, both of which are malignancies strongly associated with oncogenic strains of human papilloma virus (HPV). Interestingly, squamous cell cancer of the anal canal shares an almost identical pathophysiology including causal association with HPV. Due to this, we chose to use the TIP regimen to treat patients with advanced anal cancer at our institution and report our findings on three such consecutive patients. All the patients tolerated the regimen well with manageable side effects and had excellent responses with complete resolution of PET activity after treatment. Our observations suggest that TIP is highly active for squamous cell cancer of the anal canal and warrants further study in the treatment of this disease. PMID- 22295203 TI - Cisplatin tumor biodistribution and efficacy after intratumoral injection of a biodegradable extended release implant. AB - Local delivery of chemotherapeutic drugs has long been recognized as a potential method for reaching high drug doses at the target site while minimizing systemic exposure. Cisplatin is one of the most effective chemotherapeutic agents for the treatment of various tumors; however, its systemic toxicity remains the primary dose-limiting factor. Here we report that incorporation of cisplatin into a fatty acid-based polymer carrier followed by a local injection into the solid tumor resulted in a successful tumor growth inhibition in heterotopic mouse bladder tumor model in mice. Platinum concentration in the tumor tissue surrounding the injected implant remained above the therapeutic level up to 14 days after the injection, while the plasma levels were several orders of magnitude lower comparing to systemic delivery. The reported delivery system increased the maximum tolerated dose of cisplatin 5 times compared to systemic delivery, thus potentially improving antitumor efficacy of cisplatin in solid tumor model. PMID- 22295204 TI - Escherichia coli Isolated from Urinary Tract Infections of Lebanese Patients between 2000 and 2009: Epidemiology and Profiles of Resistance. AB - The purpose of this study was to investigate the bacterial etiology of urinary tract infections in one of the busiest hospitals of Lebanon and to examine the epidemiologic and microbiologic properties of Escherichia coli isolated from urinary tract infections of Lebanese patients over a 10-year period. Methods. This retrospective study analyzed the data generated between 2000 and 2009 (10,013 Gram-positive and Gram-negative bacteria). Bacterial identification was based on standard culture and biochemical characteristics of isolates. Antimicrobial susceptibility was tested by the disk diffusion method, and ESBL production was detected by synergy with third-generation cephalosporins and amoxiclav. Results. E. coli was the most frequent isolate throughout the ten years (60.64% of the total isolates). It was followed by Klebsiella pneumoniae and Proteus sp., Pseudomonas aeruginosa, Enterococcus sp., and Streptococcus agalactiae. E. coli occurred more frequently in women (69.8%) than in men (61.4%). The lowest percentage of susceptibility of E. coli was manifested against piperacillin and ampicillin. An increase in the production of ESBL was observed (2.3% in 2000 to 16.8% in 2009). Conclusions. The etiology of urinary tract infections and their susceptibility profiles are important to be evaluated in countries like Lebanon where a severe misuse of antibiotics at all levels is observed. PMID- 22295205 TI - Role of HER2-Targeted Agents in Adjuvant Treatment for Breast Cancer. AB - Approximately 20% of breast cancers overexpress human epidermal growth factor receptor 2 (HER2) protein, mainly as a result of gene amplification. The receptor tyrosine kinase is believed to play a critical role in the pathogenesis and further proliferation of these tumors. The application of trastuzumab, a humanized monoclonal antibody against the extracellular domain of HER2 protein, to HER2-positive metastatic breast cancer has significantly improved treatment outcomes. Following this success, several phase III trials have evaluated the role of trastuzumab in the adjuvant setting, with the result that trastuzumab use is now the standard of care for most HER2-positive early breast cancer patients. In this paper, we review these pivotal phase III trials. We also discuss unresolved issues in adjuvant treatment with trastuzumab, including target patient population, sequential or concurrent use with chemotherapy or radiation, treatment duration, cardiotoxicity, and the possibility of eliminating chemotherapy. Following confirmation of its ability to partially overcome trastuzumab resistance, we also discuss the role of lapatinib in adjuvant use. PMID- 22295206 TI - Neoadjuvant treatment in rectal cancer: actual status. AB - Neoadjuvant (preoperative) concomitant chemoradiotherapy (CRT) has become a standard treatment of locally advanced rectal adenocarcinomas. The clinical stages II (cT3-4, N0, M0) and III (cT1-4, N+, M0) according to International Union Against Cancer (IUCC) are concerned. It can reduce tumor volume and subsequently lead to an increase in complete resections (R0 resections), shows less toxicity, and improves local control rate. The aim of this review is to summarize actual approaches, main problems, and discrepancies in the treatment of locally advanced rectal adenocarcinomas. PMID- 22295207 TI - New agents targeting angiogenesis in glioblastoma. AB - Glioblastoma is the most common malignant glioma in adults, and despite recent advances in standard treatment, the prognosis still remains dismal, with a median survival of 15 months. The incorporation of bevacizumab in the standard treatment of relapsed glioblastoma has been a significant step towards combining targeted agents with chemotherapy, and there is an increasing number of new antiangiogenic agents in various stages of development, that are being tested both in relapsed and newly diagnosed disease, alone or in combination with standard treatment. The relatively favorable toxicity profile for most of them presents an advantage, but several concerns arise regarding their actual efficacy on the clinical level and the most efficient schedule of administration for each of them, as their molecular targets and patterns of action may vary significantly. This may lead to future modifications of the current rational of administering these agents concomitantly with initial chemotherapy or maintenance treatment. PMID- 22295208 TI - Development of an oral form of azacytidine: 2'3'5'triacetyl-5-azacytidine. AB - Myelodysplastic syndromes (MDSs) represent a group of incurable stem-cell malignancies which are predominantly treated by supportive care. Epigenetic silencing through promoter methylation of a number of genes is present in poor risk subtypes of MDS and often predicts transformation to acute myelogenous leukemia (AML). Azacitidine and decitabine, two FDA-approved DNA methyltransferase (DNMT) inhibitors, are able to improve overall response although their oral bioavailability complicates their clinical use. This study evaluated 2', 3', 5'-triacetyl-5-azacitidine (TAC) as a potential prodrug for azacitidine. The prodrug demonstrated significant pharmacokinetic improvements in bioavailability, solubility, and stability over the parent compound. In vivo analyses indicated a lack of general toxicity coupled with significantly improved survival. Pharmacodynamic analyses confirmed its ability to suppress global methylation in vivo. These data indicate that esterified nucleoside derivatives may be effective prodrugs for azacitidine and encourages further investigation of TAC into its metabolism, activity, and possible clinical evaluation. PMID- 22295209 TI - Breast conservation surgery: state of the art. AB - Breast conservation surgery is available to the vast majority of women with breast cancer. The combination of neoadjuvant therapies and oncoplastic surgical techniques allows even large tumours to be managed with a breast-conserving approach. The relationship between breast size and the volume of tissue to be excised determines the need for volume displacement or replacement. Such an approach can also be used in the management of carefully selected cases of multifocal or multicentric breast cancer. The role of novel techniques, such as endoscopic breast surgery and radiofrequency ablation, is yet to be precisely defined. PMID- 22295210 TI - Differential gene expression in primary breast tumors associated with lymph node metastasis. AB - Lymph node status remains one of the most useful prognostic indicators in breast cancer; however, current methods to assess nodal status disrupt the lymphatic system and may lead to secondary complications. Identification of molecular signatures discriminating lymph node-positive from lymph node-negative primary tumors would allow for stratification of patients requiring surgical assesment of lymph nodes. Primary breast tumors from women with negative (n = 41) and positive (n = 35) lymph node status matched for possible confounding factors were subjected to laser microdissection and gene expression data generated. Although ANOVA analysis (P < .001, fold-change >1.5) revealed 13 differentially expressed genes, hierarchical clustering classified 90% of node-negative but only 66% of node-positive tumors correctly. The inability to derive molecular profiles of metastasis in primary tumors may reflect tumor heterogeneity, paucity of cells within the primary tumor with metastatic potential, influence of the microenvironment, or inherited host susceptibility to metastasis. PMID- 22295211 TI - Which patients need an axillary clearance after sentinel node biopsy? AB - Sentinel lymph node biopsy (SLNB) is a safe and accurate minimally invasive method for detecting axillary lymph node (ALN) involvement in the clinically negative axilla thereby reducing morbidity in patients who avoid unnecessary axillary lymph node dissection (ALND). Although current guidelines recommend completion ALND when macro- and micrometastatic diseases are identified by SLNB, the benefit of this surgical intervention is under debate. Additionally, the management of the axilla in the presence of isolated tumour cells (ITCs) in SLNB is questioned. Particularly controversial is the prognostic significance of minimal SLNB metastasis in relation to local recurrence and overall survival. Preliminary results of the recently published Z0011 trial suggest similar outcomes after SNB or ALND when the SN is positive, but this finding has to be interpreted with caution. PMID- 22295212 TI - A Comparative Analysis of Biomarker Expression and Molecular Subtypes of Pure Ductal Carcinoma In Situ and Invasive Breast Carcinoma by Image Analysis: Relationship of the Subtypes with Histologic Grade, Ki67, p53 Overexpression, and DNA Ploidy. AB - There is a paucity of data regarding molecular subtypes of pure ductal carcinoma in situ (pDCIS). We evaluated the expression of ER, PR, HER2, Ki67, and p53 and DNA ploidy in 118 pDCIS and 100 invasive breast carcinomas (IBCAs) by routine IHC and classified them according to molecular subtypes. Quantification of biomarkers and DNA ploidy was performed by image analysis. Expression of ER, PR, and high ki67 was more frequent in pDCIS compared to IBCA. High-grade tumors had lower ER and PR expression, high Ki67, overexpression of HER2 and p53, and DNA aneuploidy. Luminal A and HER2 subtypes were more common in pDCIS, and triple negative was more prevalent in IBCA. In both groups, HER2 and triple negative subtypes were characterized by high ki67, overexpression of p53, and DNA aneuploidy compared to luminal subtypes. Molecular subtypes of IBCA are distinct from those of pDCIS. Invasion is characterized by change in phenotype in some tumors. PMID- 22295213 TI - A role for estrogen receptor phosphorylation in the resistance to tamoxifen. AB - About two thirds of all human breast cancer cases are estrogen receptor positive. The drug of first choice for these patients is tamoxifen. However, about half of the recurrences after removal of the primary tumor are or become resistant to this drug. While many mechanisms have been identified for tamoxifen resistance in the lab, at present only a few have been translated to the clinic. This paper highlights the role in tamoxifen resistance of phosphorylation by different kinases on different sites of the estrogen receptor. We will discuss the molecular pathways and kinases that are involved in phosphorylation of ERalpha and how these affect tamoxifen resistance. Finally, we will elaborate on the clinical translation of these observations and the possibility to predict tamoxifen responses in patient tumor samples before treatment onset. The findings made originally on the bench may translate into a better and personalized treatment of breast cancer patients using an old and safe anticancer drug: tamoxifen. PMID- 22295214 TI - Electric field analysis of breast tumor cells. AB - An attractive alternative treatment for malignant tumors that are refractive to conventional therapies, such as surgery, radiation, and chemotherapy, is electrical-pulse-mediated drug delivery. Electric field distribution of tissue/tumor is important for effective treatment of tissues. This paper deals with the electric field distribution study of a tissue model using MAXWELL 3D Simulator. Our results indicate that tumor tissue had lower electric field strength compared to normal cells, which makes them susceptible to electrical pulse-mediated drug delivery. This difference could be due to the altered properties of tumor cells compared to normal cells, and our results corroborate this. PMID- 22295215 TI - Image-Based Treatment Planning of the Post-Lumpectomy Breast Utilizing CT and 3TMRI. AB - Accurate lumpectomy cavity definition is critical in breast treatment planning. We compared contouring lumpectomy cavity volume and cavity visualization score (CVS) with CT versus 3T MRI. 29 patients were imaged with CT and 3T MRI. Seven additional boost planning sets were obtained for 36 image sets total. Three observers contoured the lumpectomy cavity on all images, assigning a cavity visualization score (CVS ) of 1 to 5. Measures of consistency and agreement for CT volumes were 98.84% and 98.62%, for T1 MRI were 95.65% and 95.55%, and for T2 MRI were 97.63% and 97.71%. The mean CT, T1 MRI, and T2 MRI CVS scores were 3.28, 3.38, and 4.32, respectively. There was a highly significant difference between CT and T2 scores (P < .00001) and between T1 and T2 scores (P < .00001). Interobserver consistency and agreement regarding volumes were high for all three modalities with T2 MRI CVS the highest. MRI may contribute to target definition in selected patients. PMID- 22295216 TI - Oncoplastic approaches to breast conservation. AB - When a woman is diagnosed with breast cancer many aspects of her physical, emotional, and sexual wholeness are threatened. The quickly expanding field of oncoplastic breast surgery aims to enhance the physician commitment to restore the patient's image and self-assurance. By combining a multidisciplinary approach to diagnosis and treatment with oncoplastic surgery, successful results in the eyes of the patient and physician are significantly more likely to occur. As a way to aid oncoplastic teams in determining which approach is most suitable for their patient's tumor size, tumor location, body habitus, and desired cosmetic outcome we present a review of several oncoplastic surgical approaches. For resections located anywhere in the breast, the radial ellipse segmentectomy incision and circumareolar approach for segmental resection are discussed. For resections in the upper or central breast, crescent mastopexy, the batwing incision, the hemibatwing incision, donut mastopexy, B-flap resection, and the central quadrantectomy are reviewed. For lesions of the lower breast, the triangle incision, inframammary incision, and reduction mastopexy are discussed. Surgeons who are interested in adding oncoplastic breast conserving therapies to their skill sets are encouraged to implement these surgical techniques where applicable and to seek out breast fellowships or enhanced training when appropriate. PMID- 22295217 TI - Optimization of Adjuvant Radiation in Breast Conservation Therapy: Can We Minimize without Compromise? AB - Adjuvant breast radiation therapy after breast conservation surgery is recommended as it yields significant reduction in the risk of local recurrence, and confers a potential overall survival benefit. Although the standard breast radiation regimen has historically been delivered over 5-7 weeks; more novel, shorter courses of breast radiation are currently being employed, offering the advantage of more convenience and less time-commitment. Herein, we review the recent literature substantiating these abbreviated radiation treatment approaches and the methods of delivery thereof. In addition, we discuss imaged guided techniques currently being utilized to further refine the delivery of adjuvant breast radiation therapy. PMID- 22295218 TI - Multiple Patterns of FHIT Gene Homozygous Deletion in Egyptian Breast Cancer Patients. AB - Fragile histidine triad (FHIT) gene encodes a putative tumour suppressor protein. Loss of Fhit protein in cancer is attributed to different genetic alterations that affect the FHIT gene structure. In this study, we investigated the pattern of homozygous deletion that target the FHIT gene exons 3 to 9 genomic structure in Egyptian breast cancer patients. We have found that 65% (40 out of 62) of the cases exhibited homozygous deletion in at least one FHIT exon. The incidence of homozygous deletion was not associated with patients' clinicopathological parameters including patients' age, tumour grade, tumour type, and lymph node involvement. Using correlation analysis, we have observed a strong correlation between homozygous deletions of exon 3 and exon 4 (P < 0.0001). Deletions in exon 5 were positively correlated with deletions in exon 7 (P < 0.0001), Exon 8 (P < 0.027), and exon 9 (P = 0.04). Additionally, a strong correlation was observed between exons 8 and exon 9 (P < 0.0001).We conclude that FHIT gene exons are homozygously deleted at high frequency in Egyptian women population diagnosed with breast cancer. Three different patterns of homozygous deletion were observed in this population indicating different mechanisms of targeting FHIT gene genomic structure. PMID- 22295219 TI - Molecular Mechanisms of Trastuzumab Resistance in HER2 Overexpressing Breast Cancer. AB - The epidermal growth factor receptor 2 (HER2) is a tyrosine kinase overexpressed in nearly 20% to 25% of invasive breast cancers. Trastuzumab is a humanized monoclonal antibody that targets HER2. The majority of patients with metastatic breast cancer initially respond to trastuzumab, however, within 1 year of treatment disease progresses. Several molecular mechanisms have been described as contributing to the development of trastuzumab resistance. They could be grouped as impaired access of trastuzumab to HER2, upregulation of HER2 downstream signaling pathways, signaling of alternative pathways, and impaired immune antitumor mechanisms. However, since many of them have overlapping effects, it would be of great clinical impact to identify the principal signaling pathways involved in drug resistance. Significant efforts are being applied to find other therapeutic modalities besides trastuzumab treatment to be used alone or in combination with current modalities. PMID- 22295220 TI - Intraoperative radiotherapy in the treatment of breast cancer: a review of the evidence. AB - The surgical treatment of early breast cancer has evolved from the removal of the entire breast and surrounding tissues (mastectomy) to the removal of the tumour together with a margin of healthy tissue (lumpectomy). Adjuvant radiotherapy, however, is still mainly given to the whole breast. Furthermore, external beam radiotherapy is often given several months after initial surgery and requires the patient to attend the radiotherapy centre daily for several weeks. A single fraction of radiotherapy given during surgery directly to the tumour bed (intraoperative radiotherapy) avoids these problems. The rationale and level-1 evidence for the safety and efficacy of the technique are reviewed. PMID- 22295221 TI - Metastatic deposits of breast lobular carcinoma to small bowel and rectum. AB - Breast cancer is the most frequent malignancy in women accounting for approximately 32% of all cancers, with a lifetime risk of 1 in 10. It causes considerable morbidity and mortality. Recently, the survival rate has dramatically increased due to early detection of the disease and improvement in the treatment measures. However, more than 30% of the patients develop metastatic diseases following surgical treatment, radiotherapy, hormonal therapy, or chemotherapy. Distant spread is usually found in bones, lungs, liver, brain and skin. Rarely, it spreads to bowel, spleen, gallbladder, pancreas, urinary bladder, and eyes. Breast cancer is the second commonest primary tumour responsible for gastrointestinal metastases after malignant melanoma. We report a case of a Caucasian female who developed an intestinal obstruction secondary to metastatic deposits to the small bowel and later to the rectum from breast lobular carcinoma 2 years after mastectomy, axillary clearance, radiotherapy, hormonal therapy, and transverse rectus abdominis myocutaneous (TRAM) flap for reconstruction. PMID- 22295222 TI - CXCR4 and axillary lymph nodes: review of a potential biomarker for breast cancer metastasis. AB - CXCR4 is a 7-transmembrane G-protein chemokine receptor that allows for migration of hematopoietic cells from the bone marrow to the peripheral lymph nodes. Research has shown CXCR4 to be implicated in the invasion and metastasis of several cancers, including carcinoma of the breast. CXCL12 is the ligand for CXCR4 and is highly expressed in areas common for breast cancer metastasis, including the axillary lymph nodes. Axillary lymph nodes positive for breast carcinoma have been an important component of breast cancer diagnosis, treatment, and subsequent research. The goal of this paper is to analyze the literature that has explained the pathways from CXCR4 expression to breast cancer metastasis of the lymph nodes and the prognostic and/or predictive implications of lymph node metastases in the presence of elevated CXCR4. PMID- 22295223 TI - Stromal Expression of CD10 in Invasive Breast Carcinoma and Its Correlation with ER, PR, HER2-neu, and Ki67. AB - CD10 is a cell surface zinc-dependent endopeptidase, which degrades many bioactive peptides. CD10 expression in tumour stroma is associated with biological aggressiveness of many epithelial malignancies. To date, only one study has correlated with expression of CD10 with well-known prognostic markers of breast, that is, ER, PR, HER2-neu, and tumour grade; however, its correlation with ki67 is still not studied. The aim of this study is to evaluate stromal CD10 expression in breast carcinoma and to examine its correlation with ER, PR, HER2 neu, and Ki67. Methods and Results. CD10 expression in fifty patients was assessed by immunohistochemistry and scored as negative, weak and strong. CD10 was found to be positive in stroma of 40/50 (80%) cases. Stromal CD10 showed positive correlation with tumour grade, HER2-neu (P = .000), and ki67 (P = .027), negative correlation with ER and PR. Conclusions. Hence CD10 expression correlated strongly with well-established negative prognostic markers, that is, HER2-neu and ki67 positivity, ER/PR negativity, and higher tumour grade, thus indicating that CD10 can be used as independent marker indicating poor prognosis and can be used as target for the development of novel therapies. PMID- 22295224 TI - The optimization of breast conservation. PMID- 22295225 TI - Breast cancer treatment practices in elderly women in a community hospital. AB - Background. Elderly women with breast cancer are considered underdiagnosed and undertreated, and this adversely affects their overall survival. Methods. A total of 393 female breast cancer patients aged 70 years and older, diagnosed within the years 1989-1999, were identified from the tumor registry of The Brooklyn Hospital Center. Comparisons between the 3 different subgroups 70-74, 75-79, and 80 years and older were made using the Pearson Chi Square test. Results. Lumpectomy was performed in 42% of all patients, while mastectomy was done in 46% of patients. Adjuvant therapy such as chemotherapy, radiation therapy, and hormonal therapy were done in 12%, 25%, and 38%, respectively. Forty-seven percent of patients with positive lymph nodes received chemotherapy. Eighty-six percent of patients who were estrogen receptor-positive received adjuvant hormonal therapy. Overall five-year survival was only 14% for the >=80 age group, compared to that of 32% and 35% for the 70-74 and the 75-79 age groups, respectively. Conclusions. Surgery was performed in majority of these patients, about half received lumpectomy, the other half mastectomy. Adjuvant therapies were frequently excluded, with only hormonal therapy being the most commonly used. Overall five-year survival is significantly worse in patients >=80 years with breast cancer. PMID- 22295226 TI - Prophylactic and Therapeutic Breast Conservation in BRCA1/2 Mutation Carriers. AB - Breast-conserving therapy (BCT) for sporadic breast cancer has been widely accepted by surgeons and patients alike. While BCT is associated with a higher risk of ipsilateral breast tumor recurrence (IBTR), it has not been shown to decrease overall survival (OS) in comparison with mastectomy. Many women with a BRCA1/2 mutation opt for mastectomy instead of breast-conserving measures at the time of a breast cancer diagnosis. In some cases, this is due to fear of aggressive disease, but to date, there have been no studies offering strong evidence that breast conservation should not be offered to these women. BRCA1/2 associated breast cancer has not been found to be more aggressive or resistant to treatment than comparable sporadic tumors, and no study has shown an actual survival advantage for mastectomy in appropriately treated affected mutation carriers. This paper reviews the available literature for breast conservation and surgical decision making in BRCA1/2 mutation carriers. PMID- 22295227 TI - Duct Excision is Still Necessary to Rule out Breast Cancer in Patients Presenting with Spontaneous Bloodstained Nipple Discharge. AB - Introduction. Spontaneous nipple discharge is the third most common reason for presentation to a symptomatic breast clinic. Benign and malignant causes of spontaneous nipple discharge continue to be difficult to distinguish. We analyse our experience of duct excisions for spontaneous nipple discharge to try to identify features that raise suspicion of breast cancer and to identify features indicative of benign disease that would be suitable for nonoperative management. Methods. Details of one hundred and ninety-four patients who underwent duct excision for spontaneous nipple discharge between 1995 and 2005 were analysed. Results. Malignant disease was identified in 11 (5.7%) patients, 4 invasive and 7 insitu, which was 10.2% of those presenting with bloodstained discharge. All patients with malignant disease had bloodstained discharge. Discharge due to malignant disease was more likely to be bloodstained than that due to benign causes (Fisher's exact test, 2-tailed P value = 0.00134). Conclusion. Our findings do not support a policy of conservative management of spontaneous bloodstained nipple discharge. Cases of demonstrable spontaneous bloodstained nipple discharge should undergo duct excision to prevent malignant lesions being missed. PMID- 22295228 TI - Obesity is an independent predictor of poor survival in metastatic breast cancer: retrospective analysis of a patient cohort whose treatment included high-dose chemotherapy and autologous stem cell support. AB - The purpose of the study was to identify predictors of long-term survival in metastatic breast cancer (MBC). A cohort of 96 patients, who received high-dose chemotherapy with autologous stem cell support (HD-ASCT) as part of their treatment, was analyzed. Percent long-term survival at 10 years was 24.5% (CI 17.2-34.9%) when metastasis was diagnosed and 14.4% (CI 8.7-23.9%) when MBC was diagnosed. Survival was impacted significantly by body mass index (BMI). Median overall survival from initial diagnosis or from time of metastasis for patients with BMIs <=30 and >30 (obese) was 7.1 (CI 4.4-8.7) and 3.2 years (2.41-6.75), respectively, or 3.2 or 2.3 years (all P = 0.02). Also, obesity was the only independent patient-related predictor of time to metastasis and of survival. While obesity is linked with poor outcomes in earlier stages of breast cancer, this has not been previously reported for MBC. PMID- 22295229 TI - Autophagy: friend or foe in breast cancer development, progression, and treatment. AB - Autophagy is a catabolic process responsible for the degradation and recycling of long-lived proteins and organelles by lysosomes. This degradative pathway sustains cell survival during nutrient deprivation, but in some circumstances, autophagy leads to cell death. Thereby, autophagy can serve as tumor suppressor, as the reduction in autophagic capacity causes malignant transformation and spontaneous tumors. On the other hand, this process also functions as a protective cell-survival mechanism against environmental stress causing resistance to antineoplastic therapies. Although autophagy inhibition, combined with anticancer agents, could be therapeutically beneficial in some cases, autophagy induction by itself could lead to cell death in some apoptosis resistant cancers, indicating that autophagy induction may also be used as a therapy. This paper summarizes the most important findings described in the literature about autophagy and also discusses the importance of this process in clinical settings. PMID- 22295230 TI - Subgross morphology, the sick lobe hypothesis, and the success of breast conservation. AB - Breast carcinoma has a complex subgross morphology in the majority of cases. The malignant transformation usually involves a single breast lobe and may demonstrate peripheral, segmental, or lobar growth patterns in the in situ phase. During the invasive phase, the tumor may grow beyond the borders of the affected lobe. The dimensions of the involved lobe and the pattern of its involvement determine the extent of the disease in the early phase, with the size, type, and position of the invasive foci being additional determinants in more advanced cases. Breast carcinomas of limited extent (occupying a tissue area <40 mm) are proper candidates for breast-conserving surgery. In other cases, careful individual preoperative assessment of disease extent is necessary in making decisions about the most appropriate surgical approach, taking into account the position of the lesion(s) within the breast, the dimensions of the breast, and patient preference. PMID- 22295231 TI - Metronomic Cyclophosphamide and Methotrexate Chemotherapy Combined with 1E10 Anti Idiotype Vaccine in Metastatic Breast Cancer. AB - The use of low doses of cytotoxic agents continuously for prolonged periods is an alternative for the treatment of patients with metastatic breast cancer who have developed resistance to conventional chemotherapy. The combination of metronomic chemotherapy with therapeutic vaccines might increase the efficacy of the treatment. Twenty one patients with metastatic breast cancer in progression and a Karnosky index >=60%, were treated with metronomic chemotherapy (50 mg of cyclophospamide orally daily and 2.5 mg of methotrexate orally bi-daily), in combination with five bi-weekly subcutaneous injections of 1 mg of aluminum hydroxide-precipitated 1E10 anti-idiotype MAb (1E10-Alum), followed by reimmunizations every 28 days. Five patients achieved objective response, eight showed stable disease and eight had disease progression. Median time to progression was 9,8 months, while median overall survival time was 12,93 months. The median duration of the response (CR+PR+SD) was 18,43 months (12,20-24,10 months), being higher than 12 months in 76,9% of the patients. Overall toxicity was generally mild. Metronomic chemotherapy combined with 1E10-Alum vaccine immunotherapy might be a useful therapeutic option for the treatment of metastatic breast cancer due to its potential impact on survival and patient quality of live, low toxicity and advantages of the administration. PMID- 22295232 TI - Redefining lumpectomy using a modification of the "sick lobe" hypothesis and ductal anatomy. AB - Objectives. The "Sick Lobe" hypothesis states that breast cancers evolve from entire lobes or portions of lobes of the breast where initiation events have occurred early in development. The implication is that some cancers are isolated events and others are truly multi-focal but limited to single lobar-ductal units. Methods. This is a single surgeon retrospective review of early stage breast cancer lumpectomy patients treated from 1/2000 to 2/2005. Ductal endoscopy was used direct lumpectomy surgical margins by defining ductal anatomy and mapping proliferative changes within the sick lobe for complete excision. Results. Breast conservation surgery for stage 0-2 breast cancer with an attempt to perform endoscopy in association with therapeutic lumpectomy was performed in 554 patients (successful endoscopy in 465 cases). With an average followup of >5 years for the entire group, annual hazard rate for local failure in traditional lumpectomy without ductal mapping was 0.97%/yr. and for lumpectomy with ductal mapping and excision of entire sick lobe was 0.18%/yr. With endoscopy, 42% of patients were found to have extensive disease within their "sick lobe." Conclusions. Targeting breast cancer lumpectomy using endoscopy and excision of regional associated proliferation seems associated with lower recurrence in this non-randomized series. PMID- 22295233 TI - Breast cancer preoperative staging: does contrast-enhanced magnetic resonance mammography modify surgery? AB - Women with newly diagnosed breast cancer may have lesions undetected by conventional imaging. Recently contrast-enhanced magnetic resonance mammography (CE-MRM) showed higher sensitivity in breast lesions detection. The present analysis was aimed at evaluating the benefit of preoperative CE-MRM in the surgical planning. From 2005 to 2009, 525 consecutive women (25-75 years) with breast cancer, newly diagnosed by mammography, ultrasound, and needle-biopsy, underwent CE-MRM. The median invasive tumour size was 19 mm. In 144 patients, CE MRM identified additional lesions. After secondlook, 119 patients underwent additional biopsy. CE-MRM altered surgery in 118 patients: 57 received double lumpectomy or wider excision (41 beneficial), 41 required mastectomy (40 beneficial), and 20 underwent contra lateral surgery (18 beneficial). The overall false-positive rate was 27.1% (39/144). CE-MRM contributed significantly to the management of breast cancer, suggesting more extensive disease in 144/525 (27.4%) patients and changing the surgical plan in 118/525 (22.5%) patients (99/525, 18.8% beneficial). PMID- 22295234 TI - Cancer multidisciplinary team meetings: evidence, challenges, and the role of clinical decision support technology. AB - Multidisciplinary team (MDT) model in cancer care was introduced and endorsed to ensure that care delivery is consistent with the best available evidence. Over the last few years, regular MDT meetings have become a standard practice in oncology and gained the status of the key decision-making forum for patient management. Despite the fact that cancer MDT meetings are well accepted by clinicians, concerns are raised over the paucity of good-quality evidence on their overall impact. There are also concerns over lack of the appropriate support for this important but overburdened decision-making platform. The growing acceptance by clinical community of the health information technology in recent years has created new opportunities and possibilities of using advanced clinical decision support (CDS) systems to realise full potential of cancer MDT meetings. In this paper, we present targeted summary of the available evidence on the impact of cancer MDT meetings, discuss the reported challenges, and explore the role that a CDS technology could play in addressing some of these challenges. PMID- 22295235 TI - Lymphangiogenesis and Axillary Lymph Node Metastases Correlated with VEGF-C Expression in Two Immunocompetent Mouse Mammary Carcinoma Models. AB - Lymphangiogenesis and the expression of vascular endothelial cell growth factor C (VEGF-C) in tumors have been considered to be causally promoting lymphatic metastasis. There are only a few studies on lymphatic metastasis in immunocompetent allograft mouse models. To study the relationship between VEGF-C mediated lymphangiogenesis and axillary lymph node metastasis, we used two mouse mammary carcinoma cell lines; the BJMC338 has a low metastatic propensity, whereas the BJMC3879 has a high metastatic propensity although it originated from the former cell line. Each cell line was injected separately into two groups of female BALB/c mice creating in vivo mammary cancer models. The expression level of VEGF-C in BJMC3879 was higher than BJMC338. As the parent cell line, BJMC3879 derived tumors showed higher expression of VEGF-C compared to BJMC338-derived tumors. This higher expression of VEGF-C in BJMC3879-derived tumors was associated with marked increase in infiltrating macrophages and enhanced expression of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) reflecting increased tumoral lymphatic density and subsequent induction of axillary lymph node metastasis. Our mouse mammary carcinoma models are allotransplanted tumors showing the same axillary lymph node metastatic spectrum as human breast cancers. Therefore, our mouse models are ideal for exploring the various molecular mechanisms of cancer metastasis. PMID- 22295236 TI - Evaluation of sentinel node biopsy in locally advanced breast cancer patients who become clinically node-negative after neoadjuvant chemotherapy: a preliminary study. AB - Introduction. Controversy continues over the appropriate timing of sentinel lymph node (SLN) biopsy in locally advanced breast cancer (LABC) patients receiving neoadjuvant chemotherapy. We evaluated the feasibility and accuracy of SLN biopsy in LABC patients with cytology-proven axillary nodal metastasis who become clinically node-negative after neoadjuvant chemotherapy. Materials. 30 consecutive patients with LABC, who had become clinically node-negative after 3 cycles of neoadjuvant chemotherapy, were included in the study. They were then subjected to SLN biopsy, axillary lymph node dissection, and breast surgery. Results. Sentinel nodes were successfully identified in 26 of the 30 patients, resulting in an identification rate of 86.67%, sensitivity of 83.33%, false negative rate of 20%, negative predictive value of 72.73%, and an overall accuracy of 88.46%. No complications were observed as a result of dye injection. Conclusions. SLN biopsy is feasible and safe in LABC patients with cytology positive nodes who become clinically node-negative after neoadjuvant chemotherapy. Our accuracy rate, identification rate, and false negative rate are comparable to those in node-negative LABC patients. SLN biopsy as a therapeutic option in LABC after neoadjuvant chemotherapy is a promising option which should be further investigated. PMID- 22295237 TI - Patterns of cellular distribution with the sentinel node positive for breast cancer. AB - Background. Sentinel node biopsy (SNB) represents the standard of care in breast cancer axillary evaluation. Our study aims to characterize the patterns of malignant cell distribution within the sentinel nodes (SN). Methods. In a retrospective IRB-approved study, we examined the anatomic location of the nodal area with the highest radioactive signal or most intense blue staining (hot spot) and its distance from the metastatic foci. Results. 58 patients underwent SNB between January 2006 and February 2007. 12 patients with 19 positive SN were suitable for analysis. 4 (21%) metastases were located in the nodal hilum and 15 (79%) in the cortex. 6 (31%) metastases were found adjacent to the hotspot, and 9 (47%) within 4 mm of the hotspot. Conclusions. In our pilot series, SN metastases were within 4 mm of the hotspot in 78% of the cases. Pathologic analysis focused in that area may contribute to the more accurate identification of nodal metastases. PMID- 22295238 TI - The Role of Interferon Regulatory Factor-1 (IRF1) in Overcoming Antiestrogen Resistance in the Treatment of Breast Cancer. AB - Resistance to endocrine therapy is common among breast cancer patients with estrogen receptor alpha-positive (ER+) tumors and limits the success of this therapeutic strategy. While the mechanisms that regulate endocrine responsiveness and cell fate are not fully understood, interferon regulatory factor-1 (IRF1) is strongly implicated as a key regulatory node in the underlying signaling network. IRF1 is a tumor suppressor that mediates cell fate by facilitating apoptosis and can do so with or without functional p53. Expression of IRF1 is downregulated in endocrine-resistant breast cancer cells, protecting these cells from IRF1-induced inhibition of proliferation and/or induction of cell death. Nonetheless, when IRF1 expression is induced following IFNgamma treatment, antiestrogen sensitivity is restored by a process that includes the inhibition of prosurvival BCL2 family members and caspase activation. These data suggest that a combination of endocrine therapy and compounds that effectively induce IRF1 expression may be useful for the treatment of many ER+ breast cancers. By understanding IRF1 signaling in the context of endocrine responsiveness, we may be able to develop novel therapeutic strategies and better predict how patients will respond to endocrine therapy. PMID- 22295239 TI - The role of aryl hydrocarbon receptor and crosstalk with estrogen receptor in response of breast cancer cells to the novel antitumor agents benzothiazoles and aminoflavone. AB - Many estrogen-receptor- (ER-) expressing breast cancers become refractory to ER based therapies. New antitumor drugs like aminoflavone (AF) and benzothiazoles (Bzs) have been developed and have exquisite antitumor activity in ER+MCF-7 and T47D cells and in a MCF-7 nude mouse model. ER(-) breast cancer cells like MDA-MB 231 are less susceptible. We previously found in MCF-7 cells that these drugs activate the aryl hydrocarbon receptor (AhR) via translocation to the nucleus, induction of AhR-specific DNA binding activity, and expression of CYP1A1, whose transcription is controlled by the AhR-ARNT transcription factor. CYP1A1 metabolizes AF and Bz to a species which directly or after further metabolism damages DNA. In contrast an AhR-deficient variant of MCF-7 or cells with predominantly nuclear AhR expression, such as MDA-MB 231, are resistant. Thus, these drugs, unlike other neoplastic agents, require AhR-mediated signaling to cause DNA damage. This is a new treatment strategy for breast cancers with intact AhR signaling. PMID- 22295240 TI - Should a sentinel node biopsy be performed in patients with high-risk breast cancer? AB - A negative sentinel lymph node (SLN) biopsy spares many breast cancer patients the complications associated with lymph node irradiation or additional surgery. However, patients at high risk for nodal involvement based on clinical characteristics may remain at unacceptably high risk of axillary disease even after a negative SLN biopsy result. A Bayesian nomogram was designed to combine the probability of axillary disease prior to nodal biopsy with customized test characteristics for an SLN biopsy and provides the probability of axillary disease despite a negative SLN biopsy. Users may individualize the sensitivity of an SLN biopsy based on factors known to modify the sensitivity of the procedure. This tool may be useful in identifying patients who should have expanded upfront exploration of the axilla or comprehensive axillary irradiation. PMID- 22295241 TI - The Role of Cancer Stem Cells in the Organ Tropism of Breast Cancer Metastasis: A Mechanistic Balance between the "Seed" and the "Soil"? AB - Breast cancer is a prevalent disease worldwide, and the majority of deaths occur due to metastatic disease. Clinical studies have identified a specific pattern for the metastatic spread of breast cancer, termed organ tropism; where preferential secondary sites include lymph node, bone, brain, lung, and liver. A rare subpopulation of tumor cells, the cancer stem cells (CSCs), has been hypothesized to be responsible for metastatic disease and therapy resistance. Current treatments are highly ineffective against metastatic breast cancer, likely due to the innate therapy resistance of CSCs and the complex interactions that occur between cancer cells and their metastatic microenvironments. A better understanding of these interactions is essential for the development of novel therapeutic targets for metastatic disease. This paper summarizes the characteristics of breast CSCs and their potential metastatic microenvironments. Furthermore, it raises the question of the existence of a CSC niche and highlights areas for future investigation. PMID- 22295242 TI - Molecular basis of triple negative breast cancer and implications for therapy. AB - Triple negative breast cancer is an aggressive form of breast cancer with limited treatment options and is without proven targeted therapy. Understanding the molecular basis of triple negative breast cancer is crucial for effective new drug development. Recent genomewide gene expression and DNA sequencing studies indicate that this cancer type is composed of a molecularly heterogeneous group of diseases that carry multiple somatic mutations and genomic structural changes. These findings have implications for therapeutic target identification and the design of future clinical trials for this aggressive group of breast cancer. PMID- 22295243 TI - Global breast cancer: the lessons to bring home. AB - Breast cancer is the most common cancer affecting women globally. This paper discusses the current progress in breast cancer in Western countries and focuses on important differences of this disease in low- and middle-income countries (LMCs). It introduces several arguments for applying caution before globalizing some of the US-adopted practices in the screening and management of the disease. Finally, it suggests that studies of breast cancer in LMCs might offer important insights for a more effective management of the problem both in developing as well as developed countries. PMID- 22295245 TI - Improving outcomes from breast cancer in a low-income country: lessons from bangladesh. AB - Women in low- and middle-income countries (LMICs) have yet to benefit from recent advances in breast cancer diagnosis and treatment now experienced in high-income countries. Their unique sociocultural and health system circumstances warrant a different approach to breast cancer management than that applied to women in high income countries. Here, we present experience from the last five years working in rural Bangladesh. Case and consecutive series data, focus group and individual interviews, and clinical care experience provide the basis for this paper. These data illustrate a complex web of sociocultural, economic, and health system conditions which affect womens' choices to seek and accept care and successful treatment. We conclude that health system, human rights, and governance issues underlie high mortality from this relatively rare disease in Bangladesh. PMID- 22295244 TI - The hedgehog pathway conditions the bone microenvironment for osteolytic metastasis of breast cancer. AB - The microenvironment at the site of tumor metastasis plays a key role in determining the fate of the metastasizing tumor cells. This ultimately has a direct impact on the progression of cancer. Bone is the preferred site of metastasis of breast cancer. Painful, debilitating osteolytic lesions are formed as a result of crosstalk between breast cancer cells and cells in the bone, predominantly the osteoblasts and osteoclasts. In this paper, we have discussed the temporal and spatial role of hedgehog (Hh) signaling in influencing the fate of metastatic breast cancer cells in bone. By virtue of its secreted ligands, the Hh pathway is capable of homotypic and heterotypic signaling and consequently altering the microenvironment in the bone. We also have put into perspective the therapeutic implications of using Hh inhibitors to prevent and/or treat bone metastases of breast cancer. PMID- 22295246 TI - Current operative management of breast cancer: an age of smaller resections and bigger cures. AB - Surgical resection was the first effective treatment for breast cancer and remains the most important treatment modality for curative intent. Refinements in operative techniques along with the use of adjuvant radiotherapy and advanced chemotherapeutic agents have facilitated increasingly focused breast cancer operations. Surgical management of breast cancer has shifted from extensive and highly morbid procedures, to the modern concept obtaining the best possible cosmetic result in tandem with the appropriate oncological resection. An ever growing comprehension of breast cancer biology has led to substantial advances in molecular diagnosis and targeted therapies. An emerging frontier involves the breast cancer microenvironment, as a thorough understanding, while currently lacking, represents a critical opportunity for diagnosis and treatment. Collectively, these improvements will continue to push all therapeutic interventions, including operative, toward the goal of becoming more focused, targeted, and less morbid. PMID- 22295247 TI - Role of estrogen receptor signaling in breast cancer metastasis. AB - Metastatic breast cancer is a life-threatening stage of cancer and is the leading cause of death in advanced breast cancer patients. Estrogen signaling and the estrogen receptor (ER) are implicated in breast cancer progression, and the majority of the human breast cancers start out as estrogen dependent. Accumulating evidence suggests that ER signaling is complex, involving coregulatory proteins and extranuclear actions. ER-coregualtory proteins are tightly regulated under normal conditions with miss expression primarily reported in cancer. Deregulation of ER coregualtors or ER extranuclear signaling has potential to promote metastasis in ER-positive breast cancer cells. This review summarizes the emerging role of ER signaling in promoting metastasis of breast cancer cells, discusses the molecular mechanisms by which ER signaling contributes to metastasis, and explores possible therapeutic targets to block ER driven metastasis. PMID- 22295248 TI - Bromodomain-Containing Protein 4: A Dynamic Regulator of Breast Cancer Metastasis through Modulation of the Extracellular Matrix. AB - Metastasis is an extremely complex process that accounts for most cancer-related deaths. Malignant primary tumors can be removed surgically, but the cells that migrate, invade, and proliferate at distant organs are often the cells that prove most difficult to target therapeutically. There is growing evidence that host factors outside of the primary tumors are of major importance in the development of metastasis. Recently, we have shown that the bromodomain-containing protein 4 or bromodomain 4 (Brd4) functions as an inherited susceptibility gene for breast cancer progression and metastasis. In this paper, we will discuss that host genetic background on which a tumor arises can significantly alter the biology of the subsequent metastatic disease, and we will focus on the role of Brd4 in regulating metastasis susceptibility. PMID- 22295249 TI - Why breast cancer patients seek traditional healers. AB - Traditional healing is a common practice in low and middle income countries such as Malaysia. Eighty percent of Malaysians consult traditional healers or "bomoh" at some time in their life for health-related issues. The purpose of our study was to explore why breast cancer patients visit traditional healers. This is a qualitative study utilizing in-depth interviews with 11 cancer survivors who sought both traditional and Western medicine. The findings revealed the following reasons for which patients seek traditional healers: (1) recommendation from family and friends, (2) sanction from family, (3) perceived benefit and compatibility, (4) healer credibility, and (5) reservation with Western medicine and system delay. These factors work together and are strongly influenced by the Malaysian cultural context. The issue with the Western health system is common in a developing country with limited health facilities. PMID- 22295250 TI - Expression of toll-like receptors on breast tumors: taking a toll on tumor microenvironment. AB - Breast cancer remains a major cause of death in women in the developed world. As Toll-like receptors (TLRs) are widely expressed on tumor cells and play important roles in the initiation and progression of cancer, they may thus serve as important targets and have an effective perspective on breast cancer treatment. Expression of TLRs on breast cancer cells and mononuclear inflammatory cells can promote inflammation and cell survival in the tumor microenvironment. Inflammation and cancer are related. It is well known that persistent inflammatory conditions can induce cancer formation, due to production of cytokines and chemokines, which play a crucial role in promoting angiogenesis, metastasis, and subversion of adaptive immunity. TLR signaling in tumor cells can mediate tumor cell immune escape and tumor progression, and it is regarded as one of the mechanisms for chronic inflammation in tumorigenesis and progression. This paper delineates the expression of various TLRs in promotion of inflammation and development of mammary tumors. Understanding the mechanisms through which TLRs on breast cancer cells and inflammatory cells regulate growth, survival, and metastatic progression can make them potential targets for breast cancer therapy. PMID- 22295251 TI - Metabolic syndrome and triple-negative breast cancer: a new paradigm. AB - Triple-negative breast cancers (TNBCs) are aggressive tumors with poor prognosis compared to other breast cancer subtypes. The evidence linking TNBC with the metabolic syndrome, which consists of central obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, and hypertension, has emerged from clinical studies and experiments using cell lines and mouse models. Epidemiological studies have associated abdominal obesity with increased incidence of TNBC. Additionally, insulin resistance, dyslipidemia, and hypertension are associated with increased incidence of breast cancer across all subtypes. The insulin-leptin-adiponectin axis has been implicated mechanistically in breast cancer tumorigenesis. Specifically, increased leptin and decreased adiponectin levels disrupt homeostatic signaling pathways involved in cell proliferation, survival, cell-cycle regulation, and angiogenesis. Insulin, insulin-like growth factor I (IGF-I), and epidermal growth factor receptor (EGFR) may mediate interactions between these two hormones. Further research will facilitate the development of targeted therapeutics and programs to modify lifestyle factors to modulate the insulin-leptin-adiponectin axis for TNBC. PMID- 22295252 TI - Current Status of Poly(ADP-ribose) Polymerase Inhibitors as Novel Therapeutic Agents for Triple-Negative Breast Cancer. AB - Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer that is clinically defined as lacking estrogen and progesterone receptors, as well as being ERBB2 (HER-2) negative. Without specific therapeutic targets, TNBC carries a worse prognosis than other types of breast cancer in the absence of therapy. Research has now further differentiated breast cancer into subtypes based on genetic expression patterns. One of these subtypes, basal-like, frequently overlaps with the clinical picture of TNBC. Additionally, both TNBC and basal like breast cancer link to BRCA mutations. Recent pharmaceutical advances have created a class of drugs, poly(ADP-ribose) polymerase (PARP) inhibitors, which are showing potential to effectively treat these patients. The aim of this paper is to summarize the basis behind PARP inhibitors and update the current status of their development in clinical trials for the treatment of TNBC. PMID- 22295253 TI - Posture and locomotion coupling: a target for rehabilitation interventions in persons with Parkinson's disease. AB - Disorders of posture, balance, and gait are debilitating motor manifestations of advancing Parkinson's disease requiring rehabilitation intervention. These problems often reflect difficulties with coupling or sequencing posture and locomotion during complex whole body movements linked with falls. Considerable progress has been made with demonstrating the effectiveness of exercise interventions for individuals with Parkinson's disease. However, gaps remain in the evidence base for specific interventions and the optimal content of exercise interventions. Using a conceptual theoretical framework and experimental findings, this perspective and review advances the viewpoint that rehabilitation interventions focused on separate or isolated components of posture, balance, or gait may limit the effectiveness of current clinical practices. It is argued that treatment effectiveness may be improved by directly targeting posture and locomotion coupling problems as causal factors contributing to balance and gait dysfunction. This approach may help advance current clinical practice and improve outcomes in rehabilitation for persons with Parkinson's disease.". . .postural activity should be regarded as a function in its own right and not merely as a component of movement. . ."James Purdon Martin. PMID- 22295254 TI - Evaluation of the mineral status of two ecosystems for sustainable goat rearing in the iberian peninsula. AB - The mineral status in two ecosystems typical of the Iberian Peninsula was evaluated. Ecosystem I was formed by forests and ecosystem II by hilly areas. The levels of calcium, phosphorus, magnesium, iron, copper, zinc and selenium in soils, rations and serum were measured. The concentratons of iron, copper, zinc and selenium were also checked in liver. Ecosystem I showed higher values of every mineral, except for phosphorus. Seasonal differences were recorded for rations and serum, with higher values in spring. The rations produced by both ecosystems met the mineral requirements of goats in lactation. Thus, both ecosystems are suitable for the development of an ecological goat farming system. However, extra supply of minerals, particularly calcium, may be needed in the maximum productions periods. PMID- 22295255 TI - Can classification tree analyses help improve decision making about treatments for depression and anxiety disorders? A preliminary investigation. AB - OBJECTIVE: To identify how decisions about treatment are being made in secondary services for anxiety disorders and depression and, specifically, whether it was possible to predict the decisions to refer for evidence-based treatments. METHOD: Post hoc classification tree analysis was performed using a sample from an audit on implementation of the National Institute for Health and Clinical Excellence Guidelines for Depression and Anxiety Disorders. The audit was of 5 teams offering secondary care services; they included psychiatrists, psychologists, community psychiatric nurses, social workers, dual-diagnosis workers, and vocational workers. The patient sample included all of those with a primary problem of depression (n = 56) or an anxiety disorder (n = 16) who were offered treatment from February 16 to April 3, 2009. The outcome variable was whether or not evidence-based treatments were offered, and the predictor variables were presenting problem, risk, comorbid problem, social problems, and previous psychiatric history. RESULTS: Treatment decisions could be more accurately predicted for anxiety disorders (93% correct) than for depression (55%). For anxiety disorders, the presence or absence of social problems was a good predictor for whether evidence-based or non-evidence-based treatments were offered; 44% (4/9) of those with social problems vs 100% (6/6) of those without social problems were offered evidence-based treatments. For depression, patients' risk rating had the largest impact on treatment decisions, although no one variable could be identified as individually predictive of all treatment decisions. CONCLUSIONS: Treatment decisions were generally consistent for anxiety disorders but more idiosyncratic for depression, making the development of a decision-making model very difficult for depression. The lack of clarity of some terms in the clinical guidelines and the more complex nature of depression could be factors contributing to this difficulty. Further research is needed to understand the complex nature of decision making with depressed patients. PMID- 22295256 TI - When laughing is no joking matter. PMID- 22295257 TI - Diagnosing and managing violence. AB - Available categorization systems for violence encountered in medical practice do not constitute optimal tools to guide management. In this article, 4 common patterns of violence across psychiatric diagnoses are described (defensive, dominance-defining, impulsive, and calculated) and management implications are considered. The phenomenologic and neurobiological rationale for a clinical classification system of violence is also presented. PMID- 22295258 TI - Denial of cardiac illness: consequences and management. PMID- 22295259 TI - Updates to diagnostic guidelines for Alzheimer's disease. PMID- 22295260 TI - Living with a chronic illness. PMID- 22295261 TI - A case of interdose discontinuation symptoms with venlafaxine extended release. PMID- 22295262 TI - Psychiatry has to take care of its image on-screen. PMID- 22295263 TI - A case of successful treatment of comorbid obesity and polycystic ovarian disease with add-on metformin in bipolar disorder. PMID- 22295264 TI - A case of adult asperger's syndrome previously diagnosed as frontotemporal dementia. PMID- 22295265 TI - Sertraline-associated hyponatremia and subsequent tolerability of bupropion in an elderly woman. PMID- 22295266 TI - "Sleep attacks" in a patient with Parkinson's disease and subsequent psychiatric decompensation: a case report. PMID- 22295267 TI - A case of paraneoplastic limbic encephalitis associated with ovarian teratoma and N-Methyl-d-Aspartate receptor antibodies. PMID- 22295268 TI - "I am in pain!"-a case report of illicit use of transdermal fentanyl patches. PMID- 22295269 TI - Diagnosis and management of depression in 3 countries: results from a clinical vignette factorial experiment. AB - OBJECTIVE: International differences in disease prevalence rates are often reported and thought to reflect different lifestyles, genetics, or cultural differences in care-seeking behavior. However, they may also be produced by differences among health care systems. We sought to investigate variation in the diagnosis and management of a "patient" with exactly the same symptoms indicative of depression in 3 different health care systems (Germany, the United Kingdom, and the United States). METHOD: A factorial experiment was conducted between 2001 and 2006 in which 384 randomly selected primary care physicians viewed a video vignette of a patient presenting with symptoms suggestive of depression. Under the supervision of experienced clinicians, professional actors were trained to realistically portray patients who presented with 7 symptoms of depression: sleep disturbance, decreased interest, guilt, diminished energy, impaired concentration, poor appetite, and psychomotor agitation or retardation. RESULTS: Most physicians listed depression as one of their diagnoses (89.6%), but German physicians were more likely to diagnose depression in women, while British and American physicians were more likely to diagnose depression in men (P = .0251). American physicians were almost twice as likely to prescribe an antidepressant as British physicians (P = .0241). German physicians were significantly more likely to refer the patient to a mental health professional than British or American physicians (P < .0001). German physicians wanted to see the patient in follow-up sooner than British or American physicians (P < .0001). CONCLUSIONS: Primary care physicians in different countries diagnose the exact same symptoms of depression differently depending on the patient's gender. There are also significant differences between countries in the management of a patient with symptoms suggestive of depression. International differences in prevalence rates for depression, and perhaps other diseases, may in part result from differences among health care systems in different countries. PMID- 22295270 TI - Continuity of depressive disorders from childhood and adolescence to adulthood: a naturalistic study in community mental health centers. AB - OBJECTIVE: To determine and compare rates of homotypic continuity of childhood- and adolescent-onset depression into adulthood. METHOD: This was a naturalistic, prospective cohort study of children and adolescents receiving psychiatric care at all community mental health centers in Madrid, Spain, from January 1986 to December 2007. Data were obtained from a regional registry wherein all psychiatric visits to public mental health centers are recorded. Patients received their first diagnosis of an ICD-10 F32 or F33 depressive disorder between 6 and 17 years of age and were at least 20 years old at the time of their last visit. Subjects whose first diagnosis was in childhood (aged 6-12 years: depressed-child group) and subjects whose first diagnosis was in adolescence (aged 13-17 years: depressed-adolescent group) were compared in terms of demographic characteristics, psychiatric comorbidity, and rates of homotypic continuity in adulthood. RESULTS: Five hundred twenty-eight patients with depressive disorders met inclusion criteria. The depressed-adolescent group had a higher proportion of girls (60.3%) compared to the depressed-child group, but did not differ on other demographic or clinical variables. Most subjects who later received treatment in adult mental health facilities (n = 243; 57.2%; 95% CI, 50.9-57.2) continued to be diagnosed with a depressive disorder. High rates of anxiety disorders, bipolar disorder, personality disorders, and psychotic disorders in adulthood were observed among subjects from both groups. The absence of psychiatric comorbidity prior to age 18 years was associated with homotypic continuity of depressive disorder into adulthood. CONCLUSIONS: Subjects with adolescent-onset depression and subjects without comorbid psychiatric disorders in youth appear to have a higher level of homotypic continuity into adulthood. Both children and adolescents with depressive disorders are at risk for other psychiatric disorders in adulthood. PMID- 22295271 TI - Posttraumatic stress disorder screening practices: a 2010 internet assessment of customary care. AB - OBJECTIVE: Posttraumatic stress disorder (PTSD) is a signature injury of war among returning soldiers and US National Guard and Reserve members, with symptoms even more likely on rescreening. Studies that examine health care provider screening and referral practices outside the military for these patients are needed. The objective of this study was to assess health care provider PTSD practices and barriers to care. METHOD: A 25-item, anonymous Internet questionnaire was developed as an educational needs assessment survey based on the US Department of Veterans Affairs and Department of Defense PTSD guideline and the companion, primary care-directed PTSD Screening and Referral for Health Care Providers of the National Center for PTSD. The assessment design included patient vignettes followed by multiple-choice questions and was distributed on the Internet to health care providers free of charge and without compensation. Of 1,338 participant health care providers, mainly from primary care and mental health specialties, 507 responded to the questions. Participant privacy was maintained for the self-assessment survey, and all responses were deidentified and analyzed in aggregate. Overall participant responses and subgroups of primary care and mental health questionnaire responses were scored against guidelines. Participant data responses to survey questions were collected from August 20, 2010, to October 3, 2010. RESULTS: Gaps in screening skills compared with guidelines were shown, as PTSD diagnosis questions were correctly answered by 51% of primary care and 56% of mental health providers. Real-world screening and referral differed from guidelines, as only 24% of primary care and 48% of mental health providers have a system in place to routinely screen for mental health in their patients who are returning service members. Only 25% of primary care providers had access to referral to mental health services, showing large gaps in care. Stigma associated with mental disorders was the practice barrier most frequently cited by health care providers. CONCLUSIONS: The study identified gaps in PTSD screening and linkage to care among health care providers. Further training efforts and resources are needed to screen patients and to reduce barriers to care. PMID- 22295272 TI - Role of the general practitioner in the care of patients recently discharged from the hospital after a first psychotic episode: influence of length of stay. AB - OBJECTIVE: It is unclear to what extent general practitioners are involved in the postdischarge care of patients hospitalized for a first psychotic episode and whether this involvement is influenced by length of stay in the hospital. The objectives of this study were to describe the role of the general practitioner in providing postdischarge care to patients with first-episode psychosis in terms of frequency and type of consultation and the extent of collaboration with hospital based specialist services and to determine whether decreasing length of stay was accompanied by a modification in this role. METHOD: Six months after hospital discharge, a postal questionnaire was sent to the general practitioners of patients recruited to the French STEP cohort (Schizophrenie et son Traitement: une Evaluation de la Prize en charge), a prospective study of the clinical and social determinants of care pathways and prognosis for patients hospitalized for a first psychotic episode (DSM-IV criteria) in 5 services of the La Colombiere Psychiatric Hospital, Montpellier, France. Length of stay in the hospital was dichotomized according to the median value of 35 days. Data collection took place from February 2008 to March 2009. RESULTS: Of the 121 STEP patients, 65% (n=79) had a regular general practitioner. The general practitioners had been informed by the hospital of the admission of their patient in only 17.9% (7/39) of cases. Of the general practitioners, 78.3% (47/60) had seen the patient at least once since discharge, with a median number of visits standardized over 6 months of 0.86 (range, 0-8.6). General practitioners were better informed with regard to diagnosis, date of discharge, name of psychiatrist, treatment, and community follow-up at discharge for patients with a short length of stay in the hospital, who were also more likely than those with a long length of stay to be consulting for mental health problems. CONCLUSIONS: Our findings suggest a low level of implication of general practitioners in providing postdischarge care to first episode psychotic patients, irrespective of their length of hospital stay. Yet, the general practitioner has a role to play in coordinating and providing care for somatic health problems as well as psychiatric symptoms, specifically in the case of early discharge. PMID- 22295273 TI - Patient preferences for treatment of major depressive disorder and the impact on health outcomes: a systematic review. AB - OBJECTIVE: To summarize the peer-reviewed literature on patient preferences for depression treatments and the impact of these preferences on the outcomes of treatment. DATA SOURCES: Studies were identified via a systematic search conducted simultaneously in PsycINFO and MEDLINE using EBSCOhost and EMBASE. Publications were retrieved in March 2010. STUDY SELECTION: Search terms included depression OR MDD OR major depressive disorder, patient preference, treatment preference, intervention preference, and pharmacotherapy preference. There were no restrictions on years of publication. The search was restricted to research articles written in English. DATA EXTRACTION: Fifteen articles contained unique information on patient preferences for depression treatments and their impact on depression-related outcomes. RESULTS: The patient preference literature includes a limited number of studies examining the impact of patient preferences on outcomes such as depression severity, treatment initiation, persistence and adherence, treatment engagement, the development of the therapeutic alliance, and health-related quality of life. The majority of the preference research has focused on comparisons of psychotherapy versus pharmacotherapy, with some limited information regarding comparisons of psychotherapies. Results from the research to date suggest that the impact of patient treatment preferences is mixed. The results also indicate that patient preferences have minimal impact on depression severity outcomes within the context of controlled clinical trials but may be more strongly associated with other outcomes such as entry into treatment and development of the therapeutic alliance. However, it is important to note that the literature is limited in that the impact of patient preference has been examined only through secondary analyses, and there have been few studies designed explicitly to examine the impact of patient preferences, particularly outside the context of controlled clinical trials. CONCLUSIONS: Consideration of patient preferences for depression treatments may lead to increased treatment initiation and improved therapeutic alliance. However, despite treatment guidelines and suggestions in the literature, the value of and appropriate procedures for considering patient preferences in real-world treatment decisions deserves more careful study. Further research is needed, and future studies should be conducted in more naturalistic treatment settings that examine patient preferences for other specific approaches to depression treatments including preferences related to comparisons of individual pharmacotherapies and second step treatments. PMID- 22295274 TI - A case of psychosis after use of a detoxification kit and a review of techniques, risks, and regulations associated with the subversion of urine drug tests. AB - CONTEXT: The practice of drug testing in the workplace has been adopted for US federal government employees, and many state and local governments as well as private businesses have followed suit. However, a parallel industry dedicated to subverting the results of urine drug testing has emerged with little or no regulation. EVIDENCE ACQUISITION: First, the case of a 19-year-old man who developed psychosis after the use of a detoxification kit is presented. Second, a review of the existing literature on the techniques, risks, and regulations associated with the use of drug tampering kits is provided. PubMed, Cochrane Database, and Google Scholar were searched using the keywords UDS, urine toxicology, pass the drug test, and clean UA, with no restrictions on publication date. Case reports, letters to the editor, and original research and review articles in multiple languages were reviewed, as were federal regulations and acts on the topic. The search yielded 4,082 results, of which 49 articles were selected for relevance. Some articles were later omitted as they had cited the original article and had nothing new to offer. RESULTS: Three commonly used tampering techniques are in vivo adulteration, urine substitution, and in vitro adulteration. Review of the literature regarding the risks involved with use of tampering kits yielded no results. In 1986, an executive order was issued requiring all federal employees to refrain from illicit drug use, and the 1988 Drug-Free Workplace Act precipitated the Substance Abuse and Mental Health Services Administration guidelines and their subsequent revisions. Recently, many states have made regulatory efforts to bring drug test defrauding under the ambit of law. CONCLUSIONS: Clinicians need to be aware of the tampering techniques and the possibility of false-negative urine drug tests. Cognizance of inherent risks involved with using these techniques including psychiatric and/or medical complications is also warranted. The manufacture, sale, and use of these products have little or no regulation by state or federal authorities, making them potentially dangerous and imposing new challenges in testing for abused drugs. The extent of use of these products and techniques is not known at this time and is an area that warrants further research. PMID- 22295275 TI - Dementia with lewy bodies: diagnosis and management for primary care providers. AB - OBJECTIVE: The purpose of this review is to aid primary care providers in distinguishing dementia with Lewy bodies (DLB) from Alzheimer's disease and from Parkinson's disease with dementia. Differentiating these entities has important treatment implications. DATA SOURCES: A PubMed search was undertaken using the keywords Lewy body dementia, dementia with Lewy bodies, and Lewy body disease. There were no date restrictions. Only articles in the English language were reviewed. References of selected articles were reviewed for additional sources. DATA SELECTION AND EXTRACTION: Initially, 2,967 articles were retrieved. All 3 authors participated in data selection and extraction. Articles were further selected for content specific to epidemiology, clinical presentation, diagnostic studies, treatment, and prognosis. For articles with repetitive information, the most current article was used. This resulted in a total of 62 articles included in the review. DATA SYNTHESIS: Dementia with Lewy bodies is the second leading cause of dementia after Alzheimer's disease. The core symptoms of DLB, including cognitive fluctuations, visual hallucinations, and parkinsonism, may not always be present as a triad, and clinicians may be unaware of associated symptoms. Thus, this diagnosis is frequently missed by primary care providers. Often, DLB is misdiagnosed as Alzheimer's disease, Parkinson's disease, or a primary psychiatric illness. Treatments for DLB include cholinesterase inhibitors and N methyl-D-aspartate antagonists. Antipsychotics should be avoided or used with caution. CONCLUSIONS: Dementia with Lewy bodies is an often missed diagnosis. Symptoms are often attributed to other disorders. A high clinical suspicion is helpful in accurate diagnosis, and presence of any of the core symptoms should initiate clinical suspicion of DLB. Distinguishing DLB from other disorders has important treatment implications. PMID- 22295276 TI - The role of hospital heterogeneity in measuring marginal returns to medical care: a reply to Barreca, Guldi, Lindo, and Waddell. AB - In Almond et al. (2010), we describe how marginal returns to medical care can be estimated by comparing patients on either side of diagnostic thresholds. Our application examines at-risk newborns near the very low birth weight threshold at 1500 g. We estimate large discontinuities in medical care and mortality at this threshold, with effects concentrated at "low-quality" hospitals. Although our preferred estimates retain newborns near the threshold, when they are excluded the estimated marginal returns decline, although they remain large. In low quality hospitals, our estimates are similar in magnitude regardless of whether these newborns are included or excluded. PMID- 22295277 TI - Cell signaling. Crystallizing WNT signalling. PMID- 22295278 TI - Abstracts of the AAGBI (Association of Anaesthetists of Great Britain and Ireland) Winter Scientific Meeting. January 18-20, 2012. London, United Kingdom. PMID- 22295279 TI - Spotlight issue: Microcirculation-from a clinical perspective. AB - This spotlight issue of Microcirculation contains five articles written from a clinical perspective on the role of microcirculatory abnormalities in the pathogenesis of cardiovascular disease. The reviews address issues such as the impact of modifiable (life style and environmental risk factors) and non modifiable (age) on microvascular form and function; inter- and intra-cell signaling pathways underlying microvascular dysfunction; microvascular assessment as a prognostic tool in clinical practice; and the potential impact of targeted therapeutic intervention on microvascular health. The articles also describe and evaluate methodological approaches to the assessment of microvascular function in organs such as the skin, retina, muscle and adipose tissue, and provide a perspective on how such approaches might be employed in future in disease risk stratification in large epidemiological studies. This timely edition of the journal Microcirculation highlights that while there is currently no identified unifying mechanism to explain the association between microvascular phenotype and susceptibility to disease, there is accumulating evidence that deficits in microvascular structure and function may be an early and important prodromal indicator and risk determinant in a wide range of chronic non-communicable disorders, including cardiovascular and metabolic disease. PMID- 22295280 TI - Neurodevelopmental disorders: a fragile synaptic balance. PMID- 22295281 TI - Molecular mechanisms of muscle force regulation: a role for titin? PMID- 22295282 TI - Abstracts of the 112th National Congress of the Italian Society of Internal Medicine. Rome, Italy. October 22-25, 2011. PMID- 22295283 TI - Funding troubles for evolution and ecology. AB - The human population passed the 7 billion mark last month. As the population grows, the environment, which in turn is necessary for our survival, suffers as a result of increased demand for natural resources and global warming. Key to addressing these challenges will be new knowledge provided by the evolutionary and ecological sciences. But, alarmingly, these areas are underfunded, as Cyrus Martin reports. PMID- 22295284 TI - Improving the behavioural skills of robotic agents. PMID- 22295285 TI - Joint Commission ISO announcement inspires hospital interest. PMID- 22295286 TI - What are the things you should always do? PMID- 22295287 TI - When bad things happen to good hospitals. PMID- 22295288 TI - For Baldrige winners, learning is in the journey. PMID- 22295289 TI - Quality leader focuses on compliance. PMID- 22295290 TI - Bengali masculinity and the national-masculine: some conjectures for interpretation. AB - This article examines how Bengali masculinity has been negotiated between national and ethnic/local notions of identity and suggests a new way of understanding this issue. Within the specific historiography of Bengali masculinity, concerns regarding physical strength, courage and virility of the Bengali male have been central tropes, challenged by the colonially constructed stereotype of the effeminate Bengali. The present article maps mainly nineteenth century discourses regarding Bengali masculinity and focuses on one particular strategy of three, namely, construction of a mode of mythic-historical discourse to reclaim a supposedly more masculine past for Bengali men. This suggests the notion of national-masculine as a gendered materialisation of the compensatory agency of Bengali masculinity. Shown to occur through the articulation of buddhibal in contrast with bahubal that negotiates with the hegemonic national masculine, this throws new light on the emerging prominence of the bhadralok concept of a sophisticated Bengali gentleman. PMID- 22295291 TI - Suttee Sainthood through selflessness: pain of repression or power of devotion? AB - The immolation of Hindu widows has generated much horror while remaining tenaciously mixed with clandestine admiration. Reported in many eyewitness accounts and literary works, the topic has given rise to highly contested sociocultural, legal and ideological debates, strongly linked to women's rights. But the root question has not gone away: is suttee/sati just painful female victimisation or can it also reflect powerful female agency and the power of devotion? This article examines two literary works, Maud Diver's Lilamani, in which an Englishwoman unreservedly idolises a suttee, and Krupabai Satthianadhan's Kamala, where an Indian woman expresses deep pride in sutteehood. Engaging in a search for deeper meanings, this article asks what makes these two women writers revere a suttee so totally. Can one really be a suttee-saint through selflessness, or are there some deeper meanings yet to be uncovered? A wider political interpretation is suggested to re/present the root meaning of suttee. PMID- 22295292 TI - "Lena not the only one": representations of Lena Horne and Etta Moten in the Kansas City Call, 1941-1945. PMID- 22295293 TI - In/visible men: Hurston, "sweat" and laundry icons. PMID- 22295294 TI - Polymyalgia rheumatica. Treatment produces dramatic pain relief. PMID- 22295295 TI - Health tips. When heart failure worsens. PMID- 22295296 TI - Biological leukemia treatment shows breakthrough potential. PMID- 22295297 TI - Diet high in potassium may deter stroke. PMID- 22295298 TI - Non-Hodgkin's lymphoma. Keeping it in check. PMID- 22295299 TI - Costochondritis. Chest wall pain. PMID- 22295300 TI - Chronic cough. First, find the cause. PMID- 22295301 TI - I've read that too much vitamin A can weaken bones. How much is too much? PMID- 22295302 TI - I throw out leftovers that have been in the refrigerator for a week or so, even if they don't smell bad. My husband says I'm wasting. When should leftovers be tossed? PMID- 22295303 TI - [The development of agriculture by migrants in northeastern China during the 1920's]. PMID- 22295304 TI - Where to now for paediatric cardiac surgery? PMID- 22295305 TI - Public perception of the field of plastic surgery. AB - BACKGROUND: This study aims to assess the public's understanding of the scope of the practice of plastic surgeons, to determine if there is a need to increase awareness of the nature of a plastic surgeon's work. METHODOLOGY: A cross sectional study was performed. Participants were systematically selected from the White Pages for a telephone survey. The participants' demographics were recorded. Participants were excluded if they or anyone they knew had prior interactions with a plastic surgeon. Participants selected the most common area of specialization of plastic surgeons. The final set of questions determined their choice of surgeon in three different scenarios: breast reduction, excision of skin cancer from the facial region and hand trauma. RESULTS: Two hundred and thirteen of the 257 participants were eligible to complete the survey. Sixty-five per cent were female, with 38% between the ages of 46 and 65 years. The dominant field of practice was reconstructive surgery (36%). Just 19% of participants would consult plastic surgeons across the three clinical scenarios. Dermatologists (47%) were chosen over plastic surgeons (24%) to excise skin cancers from the face. Breast surgeons (53%) were chosen over plastic surgeons (23%) to perform breast reduction surgery. In hand trauma, 58% of participants would consult a hand surgeon and merely 10% would consult with plastic surgeons. DISCUSSION: The general public's understanding of plastic surgery is poor. This may be linked to the misunderstanding of specialist titles and lack of education regarding this field. PMID- 22295306 TI - Laparoscopic versus open gastrectomy for early distal gastric cancer: a meta analysis. AB - BACKGROUND: We performed a meta-analysis in an attempt to answer whether short term outcomes and lymph nodes harvested after laparoscopy-assisted gastrectomy (LAG) are comparable to those reported after conventional open gastrectomy (COG). METHODS: Prospective randomized clinical trials were eligible if they included patients with distal gastric cancer treated by LAG versus COG. End points were operating time, intra-operative blood loss, size of wound, overall post-operative complications, time to first flatus, time to start oral intake, hospital stay and lymph nodes harvested. RESULTS: Six trials including 668 patients were included. For four of the 13 end points, the summary point estimates favoured LAG over COG; there was a significant reduction in intra-operative blood loss (weighted mean difference (WMD) -115.60, 95% confidence interval (CI) -159.16 to -72.04, P < 0.00001), size of wound (WMD -5.27, 95% CI -8.94 to -1.60, P= 0.005), overall post-operative complications (odds ratio 0.55, 95% CI 0.35 to 0.85, P = 0.008) and hospital stay (WMD -2.65, 95% CI -4.97 to -0.32, P= 0.03) for LAG. However, the combined results of the individual trials show significant longer operating time (WMD 112.98, 95% CI 60.32 to 165.64, P < 0.0001) and significant reduction in lymph nodes harvested (WMD -4.79, 95% CI -6.79 to -2.79, P < 0.00001) in the LAG group. There was no significant difference between the two groups in time to first flatus, time to start oral intake, wound infection, intra-abdominal fluid collection and abscess, anastomotic stenosis and leakage and pulmonary complications. CONCLUSION: The results of this meta-analysis suggest that LAG for early distal cancer is a feasible and safe alternative to COG, with better short term outcomes. PMID- 22295307 TI - Preoperative psychological distress and functional outcome after knee replacement. AB - BACKGROUND: Fifteen to thirty percent of patients report no or little functional improvement 12 months after total knee replacement (TKR). Self-reported psychological distress prior to knee replacement is common and there is some evidence that it may be an important determinant of poor functional outcome in the short to medium term. The aim of this study was to review systematically the literature on the relationship between preoperative psychological distress and post-operative functional outcome after TKR. METHODS: A literature search through the University of Melbourne Library Catalogue, Web of Science, SCOPUS-V.4, Medline, CINAHL PLUS, PsycINFO, Pubmed and the Cochrane Library was performed with the following key words and terms: joint replacement, arthroplasty, mental health, pre-operative distress, preoperative distress, psychological distress and knee. Additional screening of the reference lists was performed. All eligible publications were quality assessed by two independent reviewers according to the Newcastle-Ottawa Scale. RESULTS: The search found 10 cohort studies. The results of the studies were conflicting as six studies found a correlation between preoperative distress and functional outcome, whereas four did not. CONCLUSION: The results from this review are conflicting. The use of different questionnaires to assess psychological distress and functional outcome makes it difficult to draw any conclusions. Future research should focus on using appropriate scales to measure exposure and outcome. We suggest using disease-specific questionnaires to assess preoperative psychological distress and a sensitive knee-specific outcome score to assess post-operative function. PMID- 22295308 TI - Practicalities of developing a breast magnetic resonance imaging screening service for women at high risk for breast cancer. AB - BACKGROUND: Demand for screening breast magnetic resonance imaging (MRI) for women with a hereditary predisposition to breast cancer has increased since the introduction of a medicare item number. To aid future service planning, we examined the practicalities of establishing and running a breast MRI screening programme for high risk women and to describe the early outcomes of our screening programme. METHODS: We undertook a retrospective audit of prospectively collected data. Women <50 years of age with an inherited BRCA1 or BRCA2 gene mutation were invited to undergo annual breast screening with MRI in addition to mammography and clinical breast examination. We assessed process times for booking, performing and reporting MRIs; MRI findings and ease of interpretation; patient recall rate; MRI cancer detection rate; and patient satisfaction via questionnaire. RESULTS: From 2006 to 2009, 82 women completed a round one screening MRI and 45, 21 and one women completed second, third and fourth round annual MRI studies, respectively. Median MRI process times were: booking 20 min; attendance in radiology department 90 min; imaging duration 45 min; reporting by one radiologist 30 min. Of the 82 round one studies, 23 (28%) were reported as >=Breast Imaging Reporting and Data System three requiring further investigation. Of the round two and three studies completed, 13/45 (28%) and 2/21 (9%) have been recalled, respectively. Seven malignancies were detected. Questionnaires revealed women were satisfied with the service. CONCLUSIONS: Significant time, staff and equipment is required to run an effective breast MRI screening programme and this must be considered by future service providers. PMID- 22295309 TI - Serum vascular endothelial growth factor-C and lymphoangiogenesis are associated with the lymph node metastasis and prognosis of patients with colorectal cancer. AB - BACKGROUND: The study aims to investigate the relationship among serum vascular endothelial growth factor (SVEGF-C), VEGF-C expression and lymph vessel density (LVD) in tumour tissue, and their influence to colorectal carcinoma (CRC). METHODS: The SVEGF-C concentration of 110 patients with CRC and 40 healthy donors was examined by ELISA. The 110 tumour tissues and 40 normal colorectal specimens were examined by immunohistochemical staining (SP method) with VEGF-C and podoplanin (lymphatic vessel specific antibody). Kaplan-Meier survival analysis determined the influence on CRC prognosis. RESULTS: CRC SVEGF-C level (889.0 +/- 264.0 pg/mL) significantly exceeded (P = 0.000) the control level (373.2 +/- 97.3 ng/L), and was significantly higher in T3, lymph node metastasis (LNM), distant metastasis, and pTNM groups III and IV. LNM prediction sensitivity, specificity, and accuracy of SVEGF-C were 85.7, 80.0 and 83.6%, respectively (875 pg/mL cut off). VEGF-C expression was elevated in CRC versus control patients (P = 0.000), and was significantly related to LNM and pTNM stages III and IV. Mean LVD in CRC (6.3 +/- 0.7/200 HP) significantly exceeded control mean (3.0 +/- 0.7/200 HP) (P = 0.000). LVD was significantly higher in LNM and pTNM stages III and IV. SVEGF-C level was significantly higher in VEGF-C positive versus negative patients (P = 0.000), and was related to LVD (P = 0.009). Kaplan-Meier ranking of prognostic factors was SVEGF-C level (P = 0.000), VEGF-C expression (P = 0.001) and LVD (P = 0.012). CONCLUSION: SVEGF-C level, VEGF-C and LVD are related to LNM and poor prognosis in patients with CRC. SVEGF-C may be a biomarker for LNM in CRC. PMID- 22295310 TI - Perioperative risk analysis for acute respiratory distress syndrome after elective oesophagectomy. AB - BACKGROUND: Acute respiratory distress syndrome (ARDS) is a major contributor to respiratory morbidity and mortality after oesophagectomy. Several pre-, intra- and post-operative factors are thought to predispose to its development in the post-oesophagectomy period. The aim of this study was to determine factors predisposing to ARDS in the post-oesophagectomy period. METHODS: A total of 112 patients who underwent elective oesophagectomy for oesophageal cancer (gastro oesophageal adenocarcinoma and high-grade dysplasia, 93; oesophageal squamous cell carcinoma, 16; oesophageal oat cell tumour, 1; oesophageal anaplastic carcinoma, 1; oesophageal colloid carcinoma, 1) between 1 January 2003 and 31 December 2006 formed the study group in this retrospective study. The pre-, intra and post-operative data for these patients (male : female = 89:23, mean age 60.8 years) were collected from an oesophagectomy database and hospital medical records. RESULTS: The incidence of ARDS was 13%. The in-hospital mortality among ARDS cases was 20% and 1-year mortality was 40%. Various factors such as preoperative chronic respiratory disease (P-value = 0.000, odds ratio = 17.76), smoking pack-years (P-value = 0.045, odds ratio = 1.02), abnormal preoperative forced expiratory volume in 1 s (P-value = 0.009, odds ratio = 7.97), high percentage of oxygen in inspired air (P-value = 0.041, odds ratio = 1.24) and use of perioperative inotropes (P-value = 0.021, odds ratio = 4.26) were associated with ARDS. CONCLUSIONS: Preoperative physiological status as indicated by a preoperative history of chronic respiratory disease and preoperative pulmonary function influenced the post-operative outcome in our patients. The use of perioperative inotropes suggests perioperative cardiorespiratory instability, and could also predispose to the development of ARDS in the post-operative period. PMID- 22295311 TI - Common peroneal nerve decompression. AB - BACKGROUND: Common peroneal neuropathy occurs as a result of compression of the common peroneal nerve (CPN) in the fibro-osseous tunnel between the fibular neck and the tendinous arch of peroneus longus. High rates of spontaneous recovery have been reported. However, there is a subset of patients who require decompression of the CPN at the fibular neck. METHODS: We performed a retrospective analysis of patients that underwent decompressive surgery of the CPN. A total of 22 operations performed on 20 patients were analysed. Pre operative workup included clinical examination, electrophysiological testing and magnetic resonance imaging (MRI) where indicated. Post-operatively, all patients were examined clinically for neurological recovery and where indicated, electrophysiology was repeated. RESULTS: 74% of patients (14 out of 19) with motor weakness improved, as did 68% with sensory dysfunction. 69% with foot drop improved to have no foot drop, most of these were those that underwent surgery within 12 months of symptom onset (OR 14.7, 95% CI 1.4-133.5). CONCLUSION: Patients with foot drop fared significantly better if their duration of symptoms prior to surgery was less than 12 months. PMID- 22295312 TI - Outcomes of infective aneurysm repairs in the New Zealand thoracic stent database. AB - BACKGROUND: Infective thoracic aneurysms are rare and have a poor prognosis. In the past, these have been managed surgically with adjunctive antibiotic therapy. Endoluminal repair is a relatively new treatment option which may be associated with lower morbidity and mortality. METHODS: The New Zealand Thoracic Aorta Stent graft registry was interrogated between December 2001 and September 2009, selecting all patients with endoluminal repair of infective thoracic aortic aneurysms. RESULTS: Out of 184 patients on the database, four (2.2%) patients (male = 3, median age = 72) underwent endoluminal repair of an infective thoracic aortic aneurysm. The aneurysm was successfully excluded at the time of the procedure in all patients. There was a low incidence of post-procedural complications including atrial fibrillation (n = 1), pneumonia with haemoptysis (n = 1), urinary retention (n = 1) and access site seroma (n = 1). Time to discharge was mean of 26.5 days, median 22.5 days (8-53 days). One of the four patients is still alive and well at the time of reporting. Of the remaining three patients, mean survival is 486 days, median 374 days (336-748 days). CONCLUSIONS: Endoluminal repair is a treatment option for infective thoracic aneurysms, but the durability is unknown. Due to the rareness of the condition, a randomized clinical trial is unlikely to succeed. National registries such as the New Zealand Thoracic Aortic Stent provide useful information regarding this. PMID- 22295313 TI - Factors predicting the need for splenectomy in children with blunt splenic trauma. AB - BACKGROUND/PURPOSE: Non-operative management of blunt splenic trauma (BST) in children is the standard of care with a success rate of greater than 90%. This paper aims to determine the factors which could predict the need for operative intervention in children with BST. METHODS: Prospectively entered data of 69 children with BST, between 1997 and 2008, from a single tertiary level trauma centre, were retrospectively analysed. A radiologist blinded to the outcome reviewed all computed tomography scans retrospectively. RESULTS: Forty-two children had isolated BST (61%) and 27 children had associated injuries (39%). All except one survived the injury and non-operative treatment was successful in 91%. Six of the 69 children (9%) with BST underwent splenectomy. There was no independent correlation to age, gender, mechanism of injury (MOI), injury grade and the need for splenectomy, whereas haemodynamic instability within 6 h of injury defined as failed resuscitation had a 100% correlation. CONCLUSION: Haemodynamic instability, which failed to respond to resuscitation within 6 h, predicted the need for splenectomy in children with BST. Splenic injury grade assessed by computed tomography scan does not predict the need for splenectomy. PMID- 22295314 TI - Complex anal fistulas: plug or flap? AB - BACKGROUND: Rectal mucosal advancement flaps (RMAF) and fistula plugs (FP) are techniques used to manage complex anal fistulas. The purpose of this study was to review and compare the results of these methods of repair. METHODS: A retrospective review of all complex anal fistulas treated by either a RMAF or a FP at Auckland City Hospital from 2004 to 2008. Comparisons were made in terms of successful healing rates, time to failure and the use of magnetic resonance imaging. RESULTS: Overall, 70 operations were performed on 55 patients (55.7% male). The mean age was 44.9 years. Twenty-one patients (30%) had had at least one previous unsuccessful repair. Indications for repair included 57 high cryptoglandular anal (81%), 4 Crohn's anal (6%), 7 rectovaginal (10%), 1 rectourethral (1%) and 1 pouch-vaginal fistula (1%). All patients were followed up with a mean of 4.5 months. Forty-eight RMAFs (69% of total) were performed with 16 successful repairs (33%). Twenty-two FPs (31% of total) were performed with 7 successful repairs (32%, P = 0.9). In failed repairs, there was no difference in terms of mean time to failure (RMAF 4.8 months versus FP 4.1 months, P = 0.62). Magnetic resonance imaging was performed in 21 patients (37%) before the repair. The success rate in these patients was 20%. CONCLUSIONS: The results of treatment of complex anal fistulas are disappointing. The choice of operation of either a RMAF or a FP did not alter the poor healing rates of about one third of patients in each group. PMID- 22295315 TI - Profile, transport and outcomes of severe burns patients within an inclusive, regionalized trauma system. AB - BACKGROUND: Severe burns represent a challenging and complex clinical presentation, requiring highly specialized burns centres that are staffed and equipped appropriately. The integration of burns care into trauma systems has been recommended. This study describes the profile, transfer and outcomes of severe burns within an inclusive, regionalized trauma system. METHODS: A retrospective analysis of prospectively collected data from the Victorian State Trauma Registry for the period July 2001-June 2009 was performed. Major trauma cases with any burn injury were analysed. A severe burns case was defined as a total body surface area (TBSA) burned >=20%. Descriptive statistics were used to define the profile of severe burns cases, their management and in-hospital outcomes. RESULTS: For the 315 cases, the mean (standard deviation) age was 39 (22) years, and 73% were male. Fire/flames was the predominant cause (72%), and 39% sustained an inhalation injury. All paediatric (n = 37) and 98% of adult cases with a %TBSA >=20 were managed at the state's burn services. Half of the cases experienced an inter-hospital transfer. Sixty-seven percent of cases were admitted to the intensive care unit, 22% died in-hospital and the median length of stay was 31 days. CONCLUSIONS: An inclusive trauma system with burns services co-located at the major trauma services resulted in almost complete referral of severe burns cases to burns services for management. Half of the cases arrived at the burns services directly from the scene of injury, highlighting the importance of ongoing clinical education about the initial management of severe burns at non burns service hospitals. PMID- 22295316 TI - Multifocal skeletal tuberculosis masquerading as metastatic disease. PMID- 22295317 TI - Aggressive fibromatosis (desmoid tumour) of the pharynx. PMID- 22295318 TI - Takayasu's arteritis: dual-source computed tomography findings and surgical treatment. PMID- 22295319 TI - Multimedia patient education to assist the informed consent process for knee arthroscopy (Re: ANZ J. Surg. 2011; 81: 176-80). PMID- 22295320 TI - Usefulness of the Clavien-Dindo classification after pancreaticoduodenectomy. PMID- 22295321 TI - Epistaxis as a challenge faced by otolaryngologist (Re: ANZ J. Surg. 2011; 81: 336-9). PMID- 22295322 TI - Regarding carotid endarterectomy in asymptomatic patients (Re: ANZ J. Surg. 2011; 81: 211-3). PMID- 22295323 TI - Will the future be more Kinected? PMID- 22295324 TI - Papillary ependymoma of the lateral ventricle: a rare low-grade variant of an uncommon neoplasm in the adult. PMID- 22295325 TI - Sphenoid ridge meningioma presenting as ischemia stroke. PMID- 22295326 TI - Axillary arch: a unique entity. PMID- 22295327 TI - Unusual presentation of lumbar swelling. PMID- 22295328 TI - Perforated gastric volvulus post-lap fundoplication and hiatal mesh herniorrhaphy. PMID- 22295329 TI - 'La Fenetre': the Australian origins of the fenestrated skin graft. PMID- 22295330 TI - Spontaneous retropharyngeal haematoma: report of a case. PMID- 22295331 TI - Pleural ectopic hepatic tissues mimicking intrapleural dissemination of tumour. PMID- 22295332 TI - Caring and sharing: strategies for recognizing and surviving burnout in surgeons. PMID- 22295333 TI - An integrated approach to surgical audit (Re: ANZ J.Surg. 2011; 81: 313-4). PMID- 22295334 TI - Google's body browser: a useful addition to electronic anatomy resources? PMID- 22295335 TI - Intradural thoracic myolipoma. PMID- 22295336 TI - Catastrophic pulmonary and paradoxical embolism. PMID- 22295337 TI - Unusual metastasis from a rectal adenocarcinoma: penile metastasis (Re: ANZ J. Surg. 2011; 81: 102). PMID- 22295338 TI - If you are called to lead, you are called to serve. PMID- 22295339 TI - AL amyloidosis in a patient with macroglossia. PMID- 22295340 TI - Sustaining the surgical educator workforce in Australia and New Zealand. AB - BACKGROUND: The education and training of tomorrow's surgeons are predicated upon the involvement of a broad spectrum of surgical educators. Identification of the factors that influence their ongoing participation is crucial for its continuity. METHODS: A study was performed on 695 surgeons identified as having major involvement in surgical education and training using a questionnaire based on a number of educational themes. RESULTS: Four hundred and thirty-eight surgeons (63%) completed the questionnaire. The majority found teaching rewarding and would recommend it to colleagues, although fewer would advocate being a supervisor or course instructor. The highest motivating factors were sharing knowledge, enjoyment of teaching, necessity to remain up to date and the interaction that teaching provides with colleagues. Barriers included insufficient time because of other work commitments, lack of support from hospital management and intrusion on work-life balance. Surgeons saw themselves as successful in answering trainees' questions, appropriately delegating patient care, providing feedback and creating a positive learning environment. They were least confident in helping trainees to identify their learning needs and develop their learning goals. New courses were considered desirable in assessment, providing feedback and the management of underperforming trainees. CONCLUSIONS: Enjoyment of teaching, sharing knowledge and the requirement to keep up to date, motivate surgeons to teach. Lack of time for teaching, and lack of recognition and support act as barriers. Designated time for teaching, being equipped for the educational roles involved, and the provision of appropriate recognition and support are necessary to sustain this essential resource. PMID- 22295341 TI - Giant fibrovascular polyp causing complete oesophageal obstruction. PMID- 22295342 TI - How can we build mentorship in surgeons of the future? AB - BACKGROUND: In the past, surgical training has been based on traditional apprenticeship model of mentoring. To cope with the rapidly changing environment of modern surgery, the mentoring process may require significant modernization. METHODS: Literature for this review was identified by searching for the MeSH heading 'mentors' in Ovid MEDLINE, EMBASE, PsycINFO and Cochrane Library databases (1950 to September 2010). The literature was reviewed to specifically identify challenges of mentoring future surgeons and to delineate a framework to establish a mentor-mentee relationship by means of a formal mentoring scheme. RESULTS: Multidimensional approaches, models and methods of delivering mentoring are essential to meet the challenges of modern surgery. We advocate a 10-stage approach to implement a formal mentoring scheme at local, national and international levels. CONCLUSION: Formalizing the mentoring process, with local, national and international schemes, will initiate mentoring relationships and cultivate a mentoring culture. Ultimately, this will maintain and improve patient care. PMID- 22295343 TI - Solitary left axillary metastasis after curative surgery for right colon cancer. PMID- 22295344 TI - Effect of heat shock protein 47 on collagen synthesis of keloid in vivo. AB - Keloid is regarded as a fibroproliferative disorder with excessive accumulation of extracellular matrix. However, the molecular mechanism of keloid formation is not well understood and no treatment modality is consistently effective. Heat shock protein 47 (HSP47) is known as a collagen-specific molecular chaperone which plays a critical role in collagen biosynthesis. Results of our previous in vitro experiments demonstrated that HSP47 might be an important reason for excessive collagen accumulation in regard to keloid formation. Our objective is to investigate whether HSP47 has an influence on collagen metabolism in animal keloid models. The constructed plasmids, carrying HSP47-small hairpin RNA (shRNA), were transfected into animal keloid models, in comparison with the control groups. After transfection, the mRNA and protein expression of HSP47 and collage type I were detected by quantitative real-time PCR and Western blot. Both the mRNA and protein levels of HSP47 in animal keloid models were decreased dramatically after transfection of the HSP47- shRNA plasmid, in comparison with the control group. Following the down-regulation of HSP47, we found that the volume of animal keloid models and the major collagen expression were reduced correspondingly. Combining the results of our previous in vitro experiment results, we suggest that overexpression of HSP47 in keloid fibroblast cells could induce excessive collagen accumulation by enhancing collagen synthesis, which not only presents a possible mechanism of keloid formation, but also offers a therapeutic potential of RNA interference to HSP47 for the treatment of keloids and other fibroproliferative disorders. PMID- 22295345 TI - Alternative lymphatic drainage routes from the lateral heel to the inguinal lymph nodes: anatomic study and clinical implications. AB - BACKGROUND: The route of lymphatic drainage from the heel to the inguinal lymph nodes is required to be accurately evaluated for clinical needs. METHODS: Seven lower limbs from four unembalmed human cadavers were studied. Under a surgical microscope, 6% hydrogen peroxide was used to detect the lymphatic vessel on the lateral side of the heel. The vessel was then injected with a radio-opaque lead oxide mixture. The vessel was traced, photographed and radiographed to demonstrate the lymphatic pathways from the lateral heel to the inguinal lymph nodes. The final results were transferred to the computer for image analysis. RESULTS: The lymph collecting vessel arising from the skin of the fossa between the lateral malleolus and the Achilles tendon ran along the posterolateral side of the leg, deep to the superficial fascia. From the popliteal fossa to the inguinal lymph nodes, three lymphatic routes were found: (i) via the superficial tissue of the medial side of the thigh; (ii) running with the superficial femoral blood vessels; (iii) running between the sciatic nerve and the profunda femoral vessels. The number and type of lymph nodes found in the popliteal fossa and femoral triangle were different from person to person. CONCLUSION: Actual and accurate lymphatic routes from the skin above the posterolateral heel to the inguinal lymph nodes have been described. This information upgrades our anatomical knowledge and the results will be of benefit for the clinical management of trauma and malignancies in the lower limb. PMID- 22295346 TI - Co and Cr accumulation in hair after metal-on-metal hip resurfacing arthroplasty. AB - BACKGROUND: Currently, it is unclear whether Co and Cr levels are persistently elevated in the body after hip resurfacing arthroplasty (HRA). This study aimed to evaluate Co and Cr levels in the body after HRA using hair as samples. METHODS: Among 22 patients who had metal-on-metal HRA(m-o-m group) using the DePuy ASR system, scalp hair of 1.5 cm in length and 2 g in weight was collected before and at 6 and 12 months after surgery. Inductively coupled plasma-mass spectrometry (ICP-MS) was used to detect Co and Cr levels in the scalp hair. Another 22 patients with total hip replacements were randomly selected from a similar age range as controls (m-o-p group). Metal levels in hair were detected with multiple measurements and analysed by repeated measures analysis of variance. RESULTS: Both Co and Cr levels were significantly increased in the m-o m group after surgery compared with those in the m-o-p group (P < 0.01). Co levels at 6 months post-operatively were 12-fold those before surgery, and Co levels 12 months postoperatively were lower than those at 6 months, but this difference was not significant (P = 0.0805) between the two time points in the m o-m group. Cr levels were persistently elevated after surgery and were increased by 10-fold compared with those at baseline in the m-o-m group. CONCLUSIONS: Co and Cr levels in scalp hair are ideal indicators for metal levels in the body after HRA. Co and Cr levels in the body were greatly increased after metal-on metal HRA. Long-term accumulation of these metals needs to be further investigated PMID- 22295347 TI - The Hedgehog signalling pathway and its prognostic impact in human gliomas. AB - OBJECTIVE: Aberrant activation of Hedgehog signalling pathway is involved in the progression of various human tumours, such as gastric cancer, paediatric brain tumour and hepatocellular carcinoma. However, the correlation of this signalling with tumourigenesis and patients' survival of gliomas has not been well documented. The present study was undertaken to examine the expression of Hedgehog signalling pathway in gliomas to elucidate its prognostic value in this tumour. METHODS: Surgical specimens were obtained from 118 patients with primary gliomas. The expression of sonic hedgehog (Shh), its receptor patched (Ptch), and downstream transcription factor Gli1 was evaluated using immunohistochemical staining. Kaplan- Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients. RESULTS: Immunostaining revealed that the activation of Hedgehog signalling pathway was significantly associated with the Karnofsky performance scale (KPS) score and World Health Organization (WHO) grade of patients with gliomas. Especially, the positive expression rates of Shh, Ptch and Gli1 were significantly higher in patients with higher grade (P = 0.008, 0.008 and 0.01) and lower KPS score (P = 0.009, 0.009 and 0.02). Statistical analysis showed that patients expressing Shh, Ptch and Gli1 have poorer overall survival rates than those not expressing these proteins. Cox multi-factor analysis showed that KPS (P = 0.02), WHO grade (P = 0.008), Shh (P = 0.01), Ptch (P = 0.01) and Gli1 (P = 0.03) were independent prognosis factors for human gliomas. CONCLUSION: These results provide convincing evidence that the Shh-Ptch1 Gli1 signalling pathway is activated in human gliomas and correlates with clinicopathologic features as well as with prognostic parameters of the tumours. Hedgehog signalling pathway may therefore play an important role in the malignant potential and survival of gliomas. PMID- 22295348 TI - Surgical dislocation of the hip and the management of femoroacetabular impingement: results of the Christchurch experience. AB - BACKGROUND: Surgical dislocation of the hip has been developed to deal with the problems causing femoroacetabular impingement (FAI). This is a relatively recent procedure that was historically reserved for larger areas specializing in hip surgery. METHODS: We hypothesized that surgical dislocation can be used for symptomatic FAI in a typical Australasian tertiary orthopaedic centre with acceptable results. This prospective study reviews the results of 53 surgical dislocations in this setting, looking particularly at functional outcomes and early complications. RESULTS: There were significant improvements in the Western Ontario and McMaster University Osteoarthritis Index score at 1, 2, 3 and 4 years post-operatively. Western Ontario and McMaster University Osteoarthritis Index scores increased by 23, 28, 34 and 35 points, respectively (P 0.0039). There was no significant improvement in hip range of motion. There were two (4%) early failures with conversion to total hip arthroplasty, and no cases of post operative avascular necrosis of the femoral head. CONCLUSIONS: We believe that as the diagnosis of FAI and conservative nonarthroplasty surgery of the hip gains wider acceptance, it will become a procedure that should be offered to all appropriate patients in an attempt to delay or limit total hip arthroplasty in this young age group. PMID- 22295349 TI - Protocol management for patients presenting with lower GI haemorrhage saves costs and maintains outcomes. AB - BACKGROUND: Lower gastrointestinal (LGI) bleeding is a common medical problem associated with significant morbidity and mortality. Although most patients stop bleeding spontaneously without intervention and most do not re-bleed, a small number have massive haemorrhage that requires intervention to prevent shock and coagulopathy. Many choices are available in managing such patients. The clinician faces decisions regarding the timing and nature of investigations and treatment options. The aim of this study is to analyse the impact of a protocol to improve clinical practice in this area. METHODS: The protocol was based on a review of investigative patterns, and transfusion at the outset of the project. Length of stay, number of inpatient and outpatient colonoscopies, radiolabelled red blood cell (RBC) scans, blood transfusions, re-admissions, operations and deaths were compared for patients admitted prior to and following implementation of the protocol. RESULTS: The number of transfusions and RBC scans both significantly lessened after implementation of the protocol. There were no demonstrable adverse outcomes by way of mortality, length of stay and number of patients requiring operation, colonoscopies and re-admissions. CONCLUSIONS: The implementation of a protocol to manage patients with LGI bleeding is matched by a significant reduction in use of hospital resources for these patients over the same time frame. Low morbidity and mortality outcome was maintained following introduction of the protocol. PMID- 22295350 TI - Treatment of subglottic hemangiomas with propranolol: initial experience in 10 infants. AB - BACKGROUND: Subglottic hemangiomas (SGH) are a rare tumour, often associated with significant airway obstruction in infants. Current treatment options, while effective, often expose the infant to potential complications. Emerging evidence suggests a role for the beta blocker propranolol in the initial management of SGH. METHODS: We report our experience with propranolol 2 mg/kg/day in 10 consecutive cases of SGH with significant airway obstruction (age range 2-4 months). RESULTS: After a mean of 7.7 months of treatment, symptom resolution was observed in all cases and eight infants had regression and were stable. Two patients experienced regrowth after 9 months of therapy. To date, no infant has had a tracheostomy or surgical removal of the lesion. CONCLUSIONS: Early results with propranolol are promising; it is effective in controlling SGH, has a rapid onset of action, appears to obviate the need for tracheostomy and can allow tapering of the corticosteroid dose. Repeat laryngoscopy will be required to map the clinical course of these children and elucidate the long-term benefits of propranolol. PMID- 22295351 TI - Axillary lymph node dissection for malignant melanoma. AB - BACKGROUND: Malignant melanoma is a common and life-threatening malignancy that often metastasizes to lymph nodes, necessitating lymph node dissections. Dissections aim for regional disease control. Dissections often result in significant morbidity and are associated with local recurrences (LRs) in the surgical field. This study aims to ascertain the LR rate and complication rate in axillary lymph node dissections (ALND) for malignant melanoma. It also aims to identify risk factors for both LR and complications. METHODS: This retrospective clinical study involved the analysis of 74 patients who were identified by the Victorian Melanoma Service database as having ALND between 1999 and 2008. Three patients underwent bilateral ALND and three patients underwent reoperative procedures following initial incomplete dissections. Patient demographics and information on the primary tumour was collected using a prospectively kept database and histopathological reports. Operative and post-operative information was obtained through a retrospective review of clinical notes and histopathological reports. RESULTS: Twelve (16%) patients developed LR at a median follow-up time of 9.5 months, and 32 (46%) patients had a post-operative complication. Kaplan-Meier estimates revealed an overall risk of LR to be 24.96% (95% CI: 13.8%-45.1%). Cox regression analysis revealed that having a primary melanoma upon the abdomen statistically significantly increased the risk of LR in the dissected field. (Hazard ratio 3.84; 95% CI: 1.0-15.0; P = 0.048). Twenty eight (38%) patients died from disseminated disease. CONCLUSIONS: ALND is associated with a significant risk of post-operative complications. It can achieve regional disease control, but a significant risk of LR exists. If LR occurs the prognosis is very poor. PMID- 22295352 TI - Necrotizing pancreatitis presenting with pneumatosis coli and hepatic portal venous gas. PMID- 22295353 TI - Giant tumoural pseudoangiomatous stromal hyperplasia of the breast in the adolescence. PMID- 22295354 TI - Brachial artery anastomotic stenoses after supracondylar humeral fracture in children. PMID- 22295355 TI - A spontaneous cholecystocutaneous fistula. PMID- 22295356 TI - Chilaiditi syndrome and associated caecal volvulus. PMID- 22295357 TI - Ranitidine may modify the biochemical disturbance in hypertrophic pyloric stenosis. PMID- 22295358 TI - Chemosis: traumatic carotid cavernous fistula. PMID- 22295359 TI - Bilateral common carotid artery dissection following aortic dissection type A repair. PMID- 22295360 TI - Effects of fatigue on surgeon performance and surgical outcomes: a systematic review. AB - BACKGROUND: Sleep deprivation and disturbances in circadian rhythms generally lead to poor performance, but is there a link in surgery? This review aimed to determine whether fatigue has an impact on surgeon performance or surgical outcomes. METHODS: Studies were identified by searching EMBASE, CINAHL, PubMed, The Cochrane Library, Current Contents and clinical trials databases. Inclusion of relevant studies was by application of a predetermined protocol and independent assessment by two reviewers. Each included study was critically appraised for its study quality according to the methods used for Cochrane Reviews. Data from included studies were extracted by one researcher using standardized data extraction tables developed a priori and checked by a second researcher. RESULTS: From 823 potentially relevant studies, a total of 16 studies were included in this review: two randomized controlled trials, five non randomized comparative studies and nine case series. Of five studies that directly measure clinical performance, three studies reported no significant difference as a result of sleep deprivation, while two studies found increases in complications or errors. Eleven studies assessed psychomotor skill performance using a variety of simulation-based methods when a participant was rested and/or fatigued. Two randomized controlled trials reported no significant differences, while the nine remaining studies reported mixed results. Surgical residents with less surgical training/experience appeared to be more affected than more senior residents. CONCLUSION: There is little evidence, as yet, to inform the issue of the effect of fatigue on surgical performance. PMID- 22295361 TI - Outcomes in patients who underwent both laparoscopic and open inguinal hernia repairs (Re: ANZ J. Surg. 2010; 80: 381-2). PMID- 22295362 TI - Giant inguinal hernia. PMID- 22295363 TI - Successful antibiotic stewardship: are we a victim of our own success? PMID- 22295364 TI - Blunt cardiac and pericardial rupture without cardiac herniation: a diagnostic challenge. PMID- 22295365 TI - GIST metastasis to adductor longus muscle. PMID- 22295366 TI - Ciliated foregut cyst of the liver mimicking a hydatid. PMID- 22295367 TI - Acute appendicitis following colonoscopy: causality or coincidence. PMID- 22295368 TI - Management of talonavicular fracture dislocation with external fixator. PMID- 22295369 TI - Sutureless total thyroidectomy: a safe and cost-effective alternative. AB - BACKGROUND: Advanced vessel sealing devices provide an alternative to conventional ligation techniques for thyroidectomy. To date, most studies have been inadequately powered to explore differences in the infrequent post-operative complications following thyroidectomy. This study is designed to compare the outcomes of sutureless thyroidectomy and conventional thyroidectomy for recurrent laryngeal nerve (RLN) injury, permanent hypoparathyroidism, and haematoma formation. METHODS: A cohort study of consecutive patients undergoing total thyroidectomy using conventional versus sutureless techniques was performed. Sutureless thyroidectomy was performed using either Ligasure Precise (Covidien) or Harmonic Focus (Johnson and Johnson) devices. The primary outcome measures were post-operative haemorrhage, permanent RLN injury and hypoparathyroidism. Secondary outcome measures were operative time, temporary hypoparathyroidism and vocal cord dysfunction. A cost minimization analysis comparing the two techniques was performed. RESULT: From January 2006 to July 2009, 1935 consecutive patients underwent total thyroidectomy. Of these, 772 underwent conventional thyroidectomy and 1163 were performed using a sutureless technique. The mean operative time was significantly lower in the sutureless group (71 versus 86 min, P = 0.02). There was no difference in the post-operative complications of haematoma (0.78% conventional versus 1.12% sutureless, P = 0.46), permanent hypoparathyroidism (1.30% conventional versus 0.52% sutureless, P = 0.06) or permanent RLN injury (0.26% conventional versus 0.52% sutureless, P = 0.39). There was an overall cost saving of AUD$14,300 per 100 total thyroidectomy cases performed using the sutureless technique. CONCLUSIONS: Sutureless thyroidectomy is a safe and efficient way of performing total thyroidectomy and has the potential to reduce operating room costs. PMID- 22295370 TI - Developing tools to predict outcomes following cardiovascular surgery. AB - BACKGROUND: Surgical decision-making tools may help surgeons achieve better outcomes by providing more personally relevant information to patients. This paper describes approaches to developing statistical tools capable of estimating the probability of morbidity and mortality after cardiovascular surgery. Our aim is to inform surgeons about the important stages that contribute to the development of decision tools. METHODS: The key elements described include study design (data quality, cohort size, etc.) and statistical methodology for developing and testing decision tools. Mention is made of the delivery of decision tools, simplicity of use, ease of interpretation of results and accessibility. Information specific to cardiac and vascular surgery is included. RESULTS: Development of useful and effective decision tools is dependent on robust and reliable data, unambiguous outcome requirements and considerable statistical expertise. Decision tools must also be extensively tested for validity and reliability, both internally and with external data. CONCLUSION: Understanding the development and assumptions that underlie surgical decision tool development will help cardiovascular surgeons appreciate the value of applying such techniques at a clinical level. PMID- 22295371 TI - Sutureless thyroidectomy: surgical technique. AB - The technique of thyroid surgery has continued to evolve over the last 200 years. Sutureless thyroidectomy is one of the recent developments in surgical technique and is made possible by the use of vessel sealing devices. The most frequently used devices include a bipolar coagulation device (Ligasure Precise) and ultrasonic dissecting shears (Harmonic Scalpel FOCUS). The use of this technology is safe with minimal morbidity and has been shown in numerous studies to significantly decrease operative time. Over 3000 thyroid and parathyroid procedures, both open and minimally invasive, have been performed with vessel sealing devices within the University of Sydney Endocrine Surgery Unit since the technology was introduced in 2005. This manuscript discusses the technique of sutureless thyroidectomy focusing on points of difference in comparison with conventional thyroidectomy using ligatures or clips. PMID- 22295372 TI - Surgery in the setting of Hashimoto's thyroiditis. AB - BACKGROUND: Hashimoto's thyroiditis (HT) is a chronic autoimmune thyroiditis typically resulting in hypothyroidism. In itself, HT is not an indication for surgery but the co-existence of thyroid nodular disease creates diagnostic and management difficulties. Indications for thyroidectomy include risk of malignancy and pressure symptoms. While fine needle aspirate cytology is effective in the diagnosis of thyroid lesions, in HT there is increased diagnostic uncertainty. This study aimed to document the results of cytology and the rate of malignancy in HT. METHODS: Data were analysed for the period 1996-2009. All patients who underwent thyroidectomy and had a formal histological diagnosis of HT were included and compared with a control population who underwent thyroidectomy but did not have HT. In both groups, patient demographics, clinical parameters, cytology findings, operative procedure and final histology were reviewed. RESULTS: One hundred and twelve patients had histologically proven HT, with a significant female preponderance compared with controls (P = 0.002). There were no significant differences between cases and controls for type of procedure or preoperative examination findings. Incidence of hypothyroidism was increased: 17 patients (15.2% versus 1.6%; P < 0.0001), whereas thyrotoxicosis was decreased: four patients (3.6% versus 14.4%; P = 0.002). There was an increased incidence of follicular/indeterminate cytology (35.7% versus 22.1%; P = 0.001). While there was an increased false negative rate in HT, this failed to achieve statistical significance (8.8% versus 2.5%; P = 0.09). Malignancy rates were more prevalent in the setting of HT (23.2% versus 11.4%; P < 0.001). CONCLUSIONS: Given the increased rate of associated malignancy and increased diagnostic uncertainty in patients with HT, we recommend routine preoperative thyroid antibody measurement. PMID- 22295373 TI - Chest pain before and after laparoscopic cardiomyotomy for achalasia. AB - BACKGROUND: Laparoscopic cardiomyotomy usually achieves a good outcome for patients with achalasia. However, some patients continue to experience chest pain after surgery, even when symptoms such as dysphagia have resolved. In this study, we quantified chest pain and the impact of myotomy on this symptom. METHODS: In 108 patients who underwent laparoscopic cardiomyotomy, chest pain was assessed before and after surgery. A standardized questionnaire evaluated chest pain, other symptoms including odynophagia, dysphagia and regurgitation, and overall satisfaction with the outcome of surgery. RESULTS: The proportion of patients reporting chest pain was similar across all age groups and genders before and after surgery. Sixty-five (60.2%) patients reported some chest pain after surgery. Of these, 47 (72.3%) also reported dysphagia, 9 (13.8%) odynophagia and 23 (35.4%) acid regurgitation (62.3%, 11.6% and 21.7% before surgery). Following surgery, there was a significant reduction in the frequency of chest pain (daily chest pain declined from 26.9% to 5.6%). CONCLUSIONS: Chest pain is common before and after cardiomyotomy for achalasia, and it is frequently associated with dysphagia. Whilst it is less problematic after surgery, it persists in many patients. This information should be provided to individuals considering surgery for achalasia. PMID- 22295374 TI - Post-operative partial hypoparathyroidism: an under-recognized disorder. AB - BACKGROUND: Permanent hypoparathyroidism is a well-recognized complication of total thyroidectomy, and a commonly reported clinical indicator of that procedure. However, a small number of patients still require ongoing calcium supplementation post-operatively in order to avoid the symptoms of hypocalcaemia, despite a normal serum parathyroid hormone level. The aim of this study was to characterize this disorder of post-operative partial hypoparathyroidism and to identify any risk factors. METHODS: A retrospective study of patients undergoing a total thyroidectomy was performed. Patients with permanent hypoparathyroidism were excluded. Patients completed a telephone interview and had serum calcium and parathyroid hormone (PTH) measured. Patient demographics, operative indications and intervention, the number of parathyroid glands autotransplanted, the presence of ongoing symptoms and calcium requirements were documented. RESULTS: One hundred ninety-six patients participated. The overall rate of permanent hypoparathyroidism over the duration of the study was 0.77%. An additional 10 (5%) patients were identified with a normal PTH level but who were still requiring calcium supplementation to prevent the symptoms associated with hypocalcaemia and to maintain a normal serum calcium level. Nine patients were female with a mean age of 48.5 years. A mean of 1.4 parathyroid glands were autotransplanted and the mean PTH level was 3.95 pmol/L. CONCLUSION: This study demonstrates that in a small group of patients following total thyroidectomy, re vascularization of parathyroid cells may be partial, with inadequate parathyroid reserve to avoid symptoms despite measurable PTH levels. This disorder of partial hypoparathyroidism has not been previously described and represents a small but important complication of total thyroidectomy. PMID- 22295375 TI - Penetrating thoraco-abdominal injuries: the Auckland City Hospital experience. AB - BACKGROUND: Penetrating injuries to the thoraco-abdominal region are rare in New Zealand. Most are low velocity wounds and are managed by general surgeons. However, injuries to major vascular structures and the heart are best managed by a multidisciplinary approach. METHODS: In Auckland, the cardiothoracic service was located at a different site to Auckland City Hospital (ACH) prior to December 2003. In December 2003, the cardiothoracic unit relocated to ACH. To determine what changes in practice eventuated from having an on-site cardiothoracic service, we reviewed all patients who had thoraco-abdominal injuries between 1998 and 2003 and subsequently. RESULTS: There were 60 patients with thoraco-abdominal penetrating injury between December 1998 and December 2003 (Group A), and 42 patients between December 2003 and September 2008 (Group B). Twelve patients in Group A and 13 patients in Group B underwent thoracotomy. Twenty-two patients in Group A and 27 patients in Group B required operations other than thoracotomy for their injuries. There was a trend of increasing involvement of cardiothoracic surgeons post-2003, in those patients undergoing thoracotomy, but not in the non thoracotomy patients. There were six re-explorations in thoracotomy patients in the pre-2003 era: done for bleeding (3), air leak following lung resection (1) and missed cardiac injuries (2), but none in post-2003 period. There was one death in Group A but none in Group B. CONCLUSIONS: Our study demonstrates that a properly trained general surgeon can make appropriate decisions and perform life saving surgery in thoraco-abdominal stab wounds. However, the on-site availability of cardiothoracic surgeons leads to surgery with fewer complications. PMID- 22295376 TI - Clopidogrel dilemma for orthopaedic surgeons. AB - BACKGROUND: Patients medicated with clopidogrel who require orthopaedic surgery present a particular challenge. Whether in an emergency or elective situation the orthopaedic surgeon must balance the risks of ceasing clopidogrel versus the risk of increased bleeding that dual antiplatelet therapy generates. METHOD: This paper reviews the current published evidence regarding the risks of continuing clopidogrel, the risks of discontinuing clopidogrel and associated considerations such as venous thromboprophylaxis. RESULTS: Little good quality evidence exists in regard to perioperative clopidogrel for orthopaedic surgery. Available evidence across non-cardiac and cardiac surgery were assessed and presented in regards to current practices, blood loss for orthopaedic operations, risks when continuing clopidogrel, risks of stopping clopidogrel and also the consideration of venous thromboembolism. CONCLUSIONS: The patients at greatest risk, when discontinuing clopidogrel therapy, are those with drug eluting stents who may be at risk of stent thrombosis. Where possible, efforts should be made to continue clopidogrel therapy through the perioperative period, taking precautions to minimize bleeding. If the risk of bleeding is too high, antiplatelet therapy must be reinstated as soon as considered reasonable after surgery. In addition, patients on clopidogrel who sustain a fall or other general trauma need to be carefully assessed because of the possibility of occult bleeding, such as into the retroperitoneal space. Until more definitive evidence becomes available, this review aims to provide a guide for the orthopaedic surgeon in dealing with the difficult dilemma of the patient on clopidogrel therapy, recommending that orthopaedic surgeons take a team approach to assess the individual risks for all patients and consider continuation of clopidogrel therapy perioperatively where possible. PMID- 22295377 TI - Parathyroid carcinoma: increasing incidence and changing presentation. AB - BACKGROUND: Parathyroid carcinoma has been regarded as an exceedingly rare disease worldwide, responsible for less than 1% of cases of primary hyperparathyroidism. However, there have been anecdotal reports recently of an increasing number of patients presenting with parathyroid carcinoma. The aim of this study was to examine the changing incidence and presentation of parathyroid cancer within a single centre. PATIENTS AND METHODS: This is a retrospective case series. Data were obtained from the University of Sydney Endocrine Surgical Unit database, as well as a review of hospital records. All pathology was independently reviewed. RESULTS: Over the 52-year period of the study from 1958 to 2010, there were 21 cases of confirmed parathyroid cancer. Only three cases were reported in the first 30 years of the study with the majority of cases (n = 11) presenting in the last 5 years. Despite the exponential increase in presentations, no significant differences in demographics or mode of presentation were found. CONCLUSION: Possible reasons for the dramatic increase in parathyroid cancer include increased screening, an increase in referrals for parathyroid surgery overall associated with the availability of minimally invasive techniques, changes in diagnostic techniques with immunohistochemistry for parafibromin and protein gene product 9.5 (PGP9.5) or possibly a true increase in the incidence of the disease. PMID- 22295378 TI - Operative experience of general surgeons in a rural hospital. AB - BACKGROUND: There is a lack of published data on the range of procedures currently carried out by rural general surgeons. The aim of this study is to demonstrate the diversity of conditions encountered and managed by rural general surgeons, in order to determine the scope of training necessary to adequately equip trainees for rural practice. METHODS: An audit of surgical procedures completed by two surgeons over 5 years from June 2004 to June 2009 in a rural Victorian hospital was carried out. Operations were further categorized into specialty groups. RESULTS: A total of 8336 operations were completed over 5 years, by two surgeons servicing a catchment population of 54 000 people. Traditional general surgical procedures accounted for 44.3% with endoscopies accounting for a further 27.4% of cases. The remainder was accounted for by 11.8% orthopaedics, 4.5% urology, 4.4% vascular (including pacemaker insertion), 3.4% ear, nose and throat, 2.7% neurosurgery, 0.88% obstetrics and 0.42% thoracics. There was a need to be able to perform procedures well outside the field of traditional general surgery, including multisystem trauma, vascular emergencies, caesarean sections and post-partum hysterectomy. CONCLUSION: General surgeons servicing small rural communities are required to carry out a variety of procedures outside the realms of traditional general surgery. Trainees need to acquire a broad skill base, and should be competent managing surgical emergencies across all specialties. A supportive team of medical, nursing and paramedical staff are required for achieving the best outcome for patients. PMID- 22295379 TI - Nasal septum malignancy. AB - INTRODUCTION: Malignancies of the nasal septum are rare diseases and fewer than 400 cases were reported. The understanding of the disease is limited due to its rarity. METHODS: We present a series of patients with nasal septum malignancies, who were referred to the Princess Alexandra Hospital, Ear, Nose and Throat Department from 2007 to 2010. RESULTS: Seventeen patients were found to have nasal septum malignancies. The average age was 59.5 years old (range: 36 to 83 years old). The commonest initial symptom on presentation was nasal obstruction (nine out of 17, 53%), seconded by epistaxis (eight out of 17, 47%). The average time from the initial onset of symptoms to presentation averaged 18.8 months (range: 1 to 48 months). The commonest physical finding on presentation was nasal masses (11 out of 17, 65%), followed by nasal septum ulcers (four out of 17, 24%). The histology of the lesions was predominantly squamous cell carcinoma. The mean duration of follow-up was 24.7 months. The overall 3-year survival was 81.9% with the relapse free survival 66.7%. DISCUSSION: Nasal septum malignancies are highly treatable with good prognoses when in early stages. They required high degree of suspicion to be detected early. Treatment options include surgical resection and radiotherapy and they offered similar 3-year survival rate. Combined therapy is adopted in larger tumours; however, it is not verified with randomized trials. Vigilant follow-up is vital to detect early recurrence, which is common in advanced stage lesions. PMID- 22295380 TI - Familial colorectal cancer type X: polyp burden and cancer risk stratification via a family history score. AB - BACKGROUND: Patients fulfilling Amsterdam-1 criteria without mismatch repair deficiency (termed familial colorectal cancer type X (FCC type X)) were reported to have lower cancer risks than classic Lynch syndrome. This study investigates the polyp and cancer burden of this population and demonstrates relationships with a family history score (FHS). METHODS: The Jagelman Registry was queried for patients meeting Amsterdam criteria with microsatellite stable/low colorectal cancers. The risk of colorectal neoplasia was ascertained using a published FHS. Polyp distribution, histology and cumulative counts as well as extra-colonic tumours in the pedigree were reviewed. RESULTS: Twenty-one patients (9 males, 12 females) met study criteria. The median lifetime polyp count was 3 (range 1-36). FHS 8 (80%) was significantly associated with an increased risk of colorectal cancer compared with those with scores <8 who are more likely to develop polyps (P < 0.01). Twelve patients (57%) had predominantly left-sided polyps. Ten colorectal cancers (7 left-sided, 3 right-sided) were diagnosed at a median age of 48 (range 30-74) years. Only three tumours were mucinous or demonstrated tumour-infiltrating lymphocytes, typical of high microsatellite instability tumours. All patients had family history of colorectal cancers (CRCs) and at least 10 patients had a family history of uterine or breast cancer. One patient was found to have hyperplastic polyposis syndrome. CONCLUSIONS: FCC type X likely represents a heterogenous group of as yet undefined CRC predispositions. The polyp burden and cancer risk are variable and can be somewhat delineated according to an FHS. PMID- 22295381 TI - Risk factors for non-union in the non-operative management of type II dens fractures. AB - BACKGROUND: Despite the publication of numerous studies, there remains controversy regarding the non-operative treatment of type II dens fractures. The halo-thoracic vest (HTV) and rigid cervical collar are the most commonly used. We sought to compare the outcomes of patients managed with these devices in terms of risk factors for non-union and complication rates. METHODS: This study was a retrospective review of adult patients with type II dens fractures treated non operatively at a Level 1 Trauma Centre between 2001 and 2007. Patient medical records and imaging studies were reviewed. Union was defined as stable fibrous union or bony union at 3 months. RESULTS: Sixty-seven patients were included - 35 treated using a HTV and 32 with a collar. Non-union was associated with increased time in HTV or collar (P = 0.011), a mechanism of injury involving a low fall (P = 0.008), or low velocity injuries (P = 0.04). The proportion of patients with stable union at 3 months was 60% for the HTV group versus 35% for the cervical collar group (P = 0.10). There were trends to support increased risk of non-union with age >=65 years (P = 0.13) or with fracture displacement >=2 mm (P = 0.17) at the time of presentation. Clinically significant complications of the HTV were more common than those experienced with collar. Of HTV patients, 60% suffered one or more complications compared with 6% for collar. CONCLUSIONS: We were unable to demonstrate any statistically significant advantage or disadvantage of either device. Further investigation of mortality and morbidity would be beneficial. PMID- 22295382 TI - Correlation of MAPT scores with clinical and radiographic assessment of patients awaiting THR/TKR. AB - BACKGROUND: The Multi-attribute Arthritis Prioritisation Tool (MAPT) score is used as a tool to prioritize referrals to specialist clinics and care given to patients with hip and knee problems. Our pilot study aimed to determine the extent of any relationship between the MAPT scores and the clinician's assessment of severity of disease in terms of surgical waiting list (SWL) categories and radiological assessment. METHODS: This is a retrospective study of patients with symptomatic hip or knee osteoarthritis (OA) that were referred via the orthopaedic waiting list project between January and July 2009 to the Bendigo Health's orthopaedic outpatients clinic and were waitlisted for a total hip replacement (THR)/total knee replacement (TKR). The MAPT score was calculated and the Surgical waitlist Category was obtained from the surgical booking office. The radiographs of all these patients were reviewed and graded independently according to the Kellgren and Lawrence radiographic grading for severity of arthritis. The relationships between MAPT score, SWL category and the Kellgren and Lawrence radiographic grades were examined using graphical methods and Kendall's tau correlation coefficients. RESULTS: There were 62 patients in the study. The Kendall-tau sample correlation coefficient between MAPT score and the radiographic grade is tau(b) = -0.091 (P = 0.330) and between MAPT score and SWL category is tau(b) = 0.007 (P = 0.951). CONCLUSIONS: The sample data suggests that there is no significant relationship between the MAPT score and radiographic severity of OA, or between MAPT score and surgical waitlist category of patients with OA waitlisted for a THR/TKR. PMID- 22295383 TI - Clinicopathological analysis and prognostic significance of peritoneal cytology in Chinese patients with advanced gastric cancer. AB - BACKGROUND: The influence of peritoneal cytology on survival of patients with gastric cancer has not been consistent. This study was to identify risk factors for positive peritoneal cytology and to evaluate the predictive value of positive cytology among Chinese patients with advanced gastric cancer. METHODS: The study included 139 patients with gastric cancer macroscopically invading the serosa, who underwent gastrectomy and intra-operative peritoneal cytological examination. In these patients, the relationship between cytological positivity and various clinicopathological features was analysed, and survival analysis was performed to identify independent prognostic factors of significance. RESULTS: Thirty-eight (27.3%) of 139 patients had positive peritoneal cytology. Although tumour size, lymphovascular invasion, depth of tumour invasion, lymph node metastasis and peritoneal metastasis were correlated with positive cytology, multivariate analysis revealed the depth of tumour invasion and peritoneal metastasis as the independent features affecting the cytology. Patients with a positive cytology result were confirmed to have a greater risk for recurrence in the pattern of peritoneal carcinomatosis and a significant inferior prognosis. Multivariate analysis indicated that positive peritoneal cytology was an independent prognostic factor among the curatively resected patients with advanced gastric cancer and was the prognostic factor most predictive of death for these patients (risk ratio = 2.74). CONCLUSIONS: Positive peritoneal cytology correlated with advanced features of gastric cancer. It is an independent poor prognostic factor, and it may serve as a guide for adjuvant therapeutic options to improve the survival of gastric cancer. PMID- 22295384 TI - Anterior cruciate ligament reconstruction: a systematic review of polyethylene terephthalate grafts. AB - BACKGROUND: The ligament advanced reinforcement system (LARS) ligament is an artificial polyester ligament made from polyethylene terephthalate (PET) that is used for primary anterior cruciate ligament (ACL) reconstructive surgery. Recent media attention has resulted in a high awareness of this reconstructive option among patients; however, the outcomes compared with autograft are controversial. OBJECTIVES: A systematic review of the literature was undertaken to examine the outcomes following LARS and long-term PET artificial grafts in ACL reconstructive surgery. The ultimate objective was to determine whether the LARS ligament should be incorporated into routine practice. METHODS: A systematic search strategy from 1970 to June 2010 was used to retrieve relevant studies. Inclusion of articles was established through application of a predetermined protocol, independent assessment by two reviewers and a final consensus decision. RESULTS: Twelve articles met the inclusion criteria for the LARS ligament. The methodology of the identified articles was poor. Only short-term outcomes were available. These results were good with low complication rates. Eleven articles reported on other PET grafts and recorded long-term follow-up of more than 4 years. These grafts had poor outcomes and a high rate of complications. No meta-analysis was possible. CONCLUSIONS: There are surprisingly few studies reporting on LARS ligament outcomes. The literature has poor methodological quality. Short-term results for the LARS ligament appear good, with faster recovery times compared with autografts. Final short-term results are not significantly different from autograft. There is real concern that late failure and iatrogenic osteoarthritis may occur based on the results of other PET grafts. PMID- 22295385 TI - Dilemma in multifocal breast cancer - largest versus aggregate diameter. AB - BACKGROUND: Several studies have shown that multifocal breast cancer has higher risks of lymph node metastases compared to unifocal cancer. This has a significant impact on prognosis and treatment options. We investigated whether this was true in our institution. METHODS: This was a retrospective study involving 75 patients with multifocal breast cancer from the year 2000 to 2007. The data recorded were largest, aggregate and extent diameter, and outcomes measured were lymph node metastases, disease recurrence and mortality rate.We randomly selected 77 age-matched subjects with unifocal cancer from the same time period for comparison. RESULTS: The average age was 57 and 58 years for the unifocal and multifocal groups, respectively. In the multifocal group, there were 54.6% ductal, 26.7% lobular and 17.3% mixed/other cancers. The unifocal group consisted of 84.4% ductal, 6.5% lobular and 9.1% mixed/other cancers. In the multifocal group, largest diameter was available for 74 patients averaging 22.1 mm. The average diameter in unifocal cancer was 18.4 mm. Fifty-two per cent of the multifocal subjects had positive lymph nodes compared with 36% in the unifocal group. CONCLUSION: Our data showed that multifocality was associated with a higher rate of lymph node metastases. This might indicate that multifocal breast cancer reflected a heavier disease burden than unifocal cancer and should be treated more aggressively. PMID- 22295386 TI - Catheter drainage versus needle aspiration in management of large (>10 cm diameter) amoebic liver abscesses. AB - OBJECTIVES: To compare the effectiveness of percutaneous catheter drainage (PCD) and percutaneous needle aspiration (PNA) in the management of large (>10 cm diameter) amoebic liver abscesses. METHODS: Eighty-two patients with amoebic liver abscess were randomly allocated to PCD (n = 42) or PNA (n = 40). Intervention was done under ultrasonography (US) [mainly] or computed tomography guidance within 24 h of admission. PNA was repeated every 3rd day if the cavity size had not reduced to 50% of the original size, for up to three times. Persistence of cavity or of clinical symptoms was considered failure of treatment. Duration to attain clinical relief, duration of hospital stay, complications, treatment failure and deaths were recorded. RESULTS: PNA was successful in 32 (80%) patients (one aspiration in 4, two in 18 and three in 10 patients), while PCD was successful in 38 (90.5%) patients. Durations to attain clinical relief and parentral antibiotics required were significantly lesser in the PCD group. Hospital stay, although did not differ significantly, was lesser for PCD group. The only procedure-related complication due to PCD was rupture of abscess in two cases, leading to sepsis and death of one patient. Complications of PNA included pleural injury in one patient, and haemorrhage leading to subcapsular hematoma in another. CONCLUSION: PCD is a better treatment option than PNA for the management of large (>10 cm diameter) amoebic liver abscess, in terms of duration to attain clinical relief and duration for which parentral antibiotics were needed. PMID- 22295387 TI - Prognostic factors of severe foetal megacystis. AB - BACKGROUND: At antenatal ultrasound, severe megacystis implies high foetal mortality rate. Traditionally, many of these foetuses undergo termination of pregnancy. We undertook a study to investigate the prognostic factor(s) for megacystis foetuses. METHODS: 61 consecutive cases of antenatally diagnosed severe megacystis between 1988 to 2008 were reviewed from a statewide tertiary referral centre for major foetal abnormalities. The data included the ultrasonic measurements and post-mortem pathologies. RESULTS: Mean gestational age (GA) at diagnosis was 17.0 weeks (range 11 to 39). The average bladder diameters for GA 10 to 14 weeks, 15 to 26 weeks, and 27 to 39 weeks were 32.5 mm, 45.7 mm, and 57.2 mm respectively. In males the most common cause of megacystis was posterior urethral valves in 32.6% (n = 17). The most common cause in females was urethral stenosis in 33% (n = 3). We compared the relative bladder size (as a percentage of normal for that gestational age) between the survivor group (n = 14) and the foetal/neonatal death group (n = 17). All terminations (n = 20) were excluded. The bladder sizes of the two groups were almost identical (310.2 +/- 108% vs. 309.8 +/- 120%). We analysed various prognostic factors. Megacystis foetuses with oligohydramnios had an increased risk of death compared to those who had megacystis without oligohydramnios (OR = 6.0; 95% CI 1.26 - 28.5, Chi-square: P = 0.019). CONCLUSION: Relative bladder size alone does not predict survival. The combination of severe megacystis and oligohydramnios implies complete obstruction of bladder outlet and is associated with high mortality rate. This provides clinicians with measurable evidence to predict survival. It also gives parents the option of avoiding unnecessary termination of pregnancy. PMID- 22295388 TI - Open repair of the acutely torn Achilles tendon under local anaesthetic. AB - BACKGROUND: Where surgery has been preferred, the torn Achilles tendon (AT) has most commonly been repaired under general or spinal anaesthetic (GA). Repair using local anaesthetic (LA) has been reported, but does not appear to be widely used. METHODS: We retrospectively reviewed 87 patients, following open repair using either GA or LA at Nelson Hospital, 2001-2005. Calf strength and ankle range of motion (ROM) were assessed. Subjective pain and function were assessed using the American Academy of Orthopaedic Surgeons Foot and Ankle Questionnaire. Complications, time off work and sport, time in theatre, and hospital were recorded. RESULTS: Fifty-nine tendons were repaired under GA (68%) and 28 under LA (32%). Outcomes were similar for each group. There was no significant difference in strength and ROM. Foot and Ankle Questionnaire scores were similar. Total theatre time averaged 57 min for GA and 37 min for LA (P = 0.01). LA repairs (82%) were performed as a day case compared with 10% of the GA repairs (P = 0.01). LA patients had a quicker return to work. GA complications included two deep vein thromboses and two pulmonary emboli. One patient from each group had a re-rupture. CONCLUSION: A repair of the acutely ruptured AT under LA is at least as effective as repair under GA with regard to function, long-term pain and patient satisfaction. LA repair results in significant cost savings due to less theatre time, fewer anaesthetic costs, and a shorter hospital stay. PMID- 22295389 TI - Surgical oncology issues in locally advanced rectal cancer. AB - The management of locally advanced (T3/4) rectal cancer is evolving. Randomized trials have shaped the current adjuvant treatment options, but yet there remain many unanswered questions. These include how best to define which patients to treat and choosing between short-course radiotherapy and long-course chemoradiotherapy. With respect to surgery, the optimal timing, the surgical approach in abdominoperineal resections and the role of laparoscopic surgery remain active areas of research. The possibility of avoiding surgery in selected patients is also a topic of great interest. A multidisciplinary team approach in managing rectal cancer patients is popular where possible and recommended in some guidelines. PMID- 22295390 TI - Preoperative factors prolonging the length of stay in elective colorectal surgery. AB - BACKGROUND: In elective colorectal resections, the patient's preoperative social situation may play a significant role in delaying their discharge from hospital. The aim of this study was to identify which preoperative factors are associated with non-medical reasons for a delay in discharge and prolonged length of stay (LOS) in hospital after elective colorectal resections. METHODS: A retrospective review of prospectively collected data was performed on all the elective colorectal resections done at Westmead Hospital for over 2 years between 2007 and 2008. LOS, whether there was a delay in discharge because of non-medical reasons, preoperative factors such as sex, age, marital status, country of birth, use of an interpreter, any children, type of residence, use of community services, American Society of Anaesthesiology (ASA) score, and whether the patient lives on their own, is a sole carer or requires help with activities of daily living were recorded. RESULTS: Overall median age was 66 years (58-75 years). Median post operative LOS for patients not delayed in discharge was 8 days and 15 days for patients with an identifiable non-medical reason for delay (P < 0.0001). Preoperative factors significantly associated with a delay included advanced age (odds ratio (OR): 10.5; 95% confidence interval (CI): 3.0-37.7; P < 0.0001), being widowed (OR: 3.5; 95% CI: 1.2-10.2; P = 0.02) and living in a retirement village (OR 15.4; 95% CI: 1.6-150.3; P = 0.019). Higher ASA scores strongly correlated with longer LOS. CONCLUSION: This study confirms that preoperative factors are important in contributing to non-medical delays in discharge and longer post-operative LOS after elective colorectal resections. PMID- 22295391 TI - Extralobar pulmonary sequestration in association with congenital cystic adenomatoid malformation: an unusual abdominal mass. PMID- 22295392 TI - Abdominal tuberculosis: an easily forgotten diagnosis. PMID- 22295393 TI - Comparing sterile bag rubbing and paint on technique in skin preparation of the hands. AB - BACKGROUND: The aim of this study was to compare two techniques for surgical site skin preparation in hand surgery. METHODS: We compared the standard sponge paint technique versus a plastic bag immersion technique using a 10% povidone-iodine with alcohol solution (Betadine, ORION Laboratories Pty Ltd, Balcatta,WA,Australia) to prepare surgical site skin for hand surgery. This sterile bag rubbing technique involves using a sterile plastic bag filled with 60 mL of Betadine solution to immerse the subjects' hand. Samples were taken from 10 subjects for bacteria colony-forming unit (CFU) counts before and 3 min after surgical site preparation in each group. Outcome measures were preparation time and CFU reduction with a plate impression test using commercially available agar slides. RESULTS: The sterile bag rubbing technique significantly reduced (P < 0.0001) the time required for surgical site skin preparation (28 s) compared with the standard technique (86 s). Both techniques were found to have similar efficacy in the reduction of CFU. CONCLUSIONS: The sterile bag rubbing technique is a quicker alternative method for surgical site preparation in hand surgery and has comparable efficacy to the widely practised standard paint-on technique. PMID- 22295394 TI - Incidental small renal mass: current management. AB - BACKGROUND: To review options for minimally invasive urological surgery in the management of incidental small renal masses (<4 cm in size). METHODS: The National Library of Medicine (PubMed) and MEDLINE databases were accessed to specifically search the available literature on minimally invasive urological surgery. Identified articles were then selected based on their contribution to the current evidence base. RESULTS: There has been an influx of articles pertaining to the management of small renal masses. Treatment options continue to evolve and thus, the scope of articles was reduced to the last ten years. All data are observational statistics, and as such, are subject to selection bias and other problems inherent in non-randomized retrospective designs. CONCLUSION: Selected cases of small renal masses can be observed with low risk of metastases, but this does not equate to zero risk. Nephron sparing surgery such as laparoscopic partial nephrectomy or open partial nephrectomy offers optimal oncological outcomes, nephron preservation and improved general prognosis. While there are no 'gold standards' in the management of the small renal mass, laparoscopic partial nephrectomy has demonstrated improving outcomes and minimal complications in the hands of an experienced surgeon. The challenge will be to encourage adoption of this technique, to ensure proficiency, but also be cognisant of the potential risks for lower volume surgeons. The role of ablative procedures is limited to the poor surgical candidate, and as an alternative to the technically difficult laparoscopic procedure. Until long-term data is available, this position is unlikely to change. PMID- 22295395 TI - Changing incidence of non-melanoma skin cancer in New Zealand. AB - BACKGROUND: Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the commonest types of non-melanoma skin cancer (NMSC). The incidence of NMSC has been increasing globally with Australia recording a 1.5-fold increase over the last 17 years. The incidence of NMSC in New Zealand is currently unknown. Given that Australia and New Zealand share similar latitude, sun exposure levels, and other risk factors, it is conceivable this increase has also occurred in New Zealand. This study aimed to provide an analysis of the incidence of NMSC within the Central Region of New Zealand based on longitudinal data derived from pathology reports. METHODS: This retrospective study examined the pathology records of 26 411 patients who underwent surgical excision for 54 004 NMSC lesions which were histologically confirmed, over a 10-year period from 1 January, 1997 to 1 January, 2007, within the Central Region of New Zealand. RESULTS: Over the study period, 50 411 primary NMSC lesions were excised. The age standardized incidence for NMSC, BCC and SCC was 406, 299 and 118 per 100 000, respectively. Since 1999, the annual incidence of BCC and SCC has increased by 4.0% and 1.1%, respectively, with the greatest increases seen in the population over the age of 50 years. CONCLUSION: New Zealand has one of the highest incidence of NMSC in the world. The high and increasing incidence of NMSC underscores the importance for the development and implementation of a national health-care delivery model, and a commitment to continued monitoring of the NMSC problem. PMID- 22295396 TI - Post laryngectomy speech and voice rehabilitation: past, present and future (Re: ANZ J. Surg. 2010; 80: 770-1). PMID- 22295397 TI - Optional inferior vena cava filter use in surgical patients: a Western Australian experience. AB - BACKGROUND: The optional filter is gaining ground, supplementing anticoagulation in the management of venous thromboembolism (VTE) in high-risk surgical patients, this despite knowledge gaps relating to its efficacy. We studied the literature and audited our experience with inferior vena cava filters to educate ourselves on this mode of VTE prophylaxis, particularly its practical implications, if any, for the surgeon. METHODS: A retrospective clinical study on inferior vena cava filter (IVCF)-related events in a Western Australian tertiary centre in 2008 was performed. Literature on IVCFs was reviewed. RESULTS: The 118 IVCF-related events at our centre in 2008, involved either Recovery-G2 75(88%) or Cook-Celect nine (11%). Of these, 78 were insertions and 36 were retrievals with four failed retrievals (10% of the attempts). Major indications for insertion included multi trauma 32 (38%), prothrombotic state 29 (34%), head injury/intracranial bleeding 16 (19%) and others eight (9%). The mean dwelling time was 100 days (12-349 days). The mean age was 43 and the retrieval rate was 58%. CONCLUSION: Optional filters have presented both versatility and challenge to the management of VTE in high-risk patients. An underlying concern about the quintessential efficacy of IVCFs lingers on, while the impact of lost follow-ups in young patients is still at large. Class 1 studies on optional filters would add certainty to the use of this generation of filters, be a step forward in relevance from the seminal work of Decousus and garner the willingness needed to engage teamwork and institutional proactiveness against loopholes such as lost follow-ups that can undermine the portrayed benefits of a potentially lifesaving device. PMID- 22295398 TI - Calculus in megalourethra presented as an ejaculatory dysfunction in an adult. PMID- 22295400 TI - Liver tumours in patients with Abernethy malformation. PMID- 22295401 TI - Stress and strain behaviour modelling of the carotid bifurcation. AB - BACKGROUND: The aim of this study is to investigate the biomechanical stress and strain behaviour within the wall of the artery and its influence on plaque formation and rupture using computational fluid dynamics (CFD). METHODS: A three dimensional finite-element model of the carotid bifurcation was generated to analyse the wall stress and strain behaviour. Both single-layer and multilayer models were created and structural analysis was compared between these two types of models. Systolic pressure of 180 mm Hg (~24 kPa) was applied in the inner boundary of the carotid bifurcation, and CFD analysis was performed to show the wall shear stress and pressure. RESULTS: The highest wall stress was found at the carotid bifurcation. When a high blood pressure (280 mm Hg) was applied to the carotid CFD model, the results showed that the stress at the carotid bifurcation may reach the rupture value. The multilayer carotid bifurcation model behaved differently from the equivalent single-layer model, with peak stress (Von-Mises) being higher in the multilayer model. CONCLUSION: The peak stress and strain was located at the origins of the internal and external carotid arteries. Significant shearing occurred between the layers in the wall of the artery at the bifurcation. Intramural shear stress in the CFD multilayer model has potential for intramural vascular injury. This may be responsible for plaque formation, plaque rupture and an injury/healing cycle. PMID- 22295402 TI - Results of LBDEx via choledochotomy (Re: ANZ J. Surg. 2011; 81: 300). PMID- 22295403 TI - Chronic refractory osteomyelitis as a part of synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome: a diagnostic challenge. PMID- 22295404 TI - Damage control surgery for liver rupture following selective internal radiation therapy for unresectable colorectal liver metastases. PMID- 22295405 TI - Tuberculous tenosynovitis with rice body formation. PMID- 22295406 TI - A novel use for the round ligament of the liver in a complicated bile duct operation. PMID- 22295407 TI - Post-operative risk factor control following internal carotid artery intervention. AB - BACKGROUND: Patients who undergo carotid surgical interventions remain at significant risk of further vascular events post-operatively. This study evaluates the level of risk factor monitoring and control being achieved post operatively for patients who undergo carotid surgical interventions within Southern Health and investigates the significance of patient education and patient insight in this context. METHODS: The study included all patients who underwent successful carotid endarterectomy (CEA) or carotid angioplasty within Southern Health during the 5-year study period. To ascertain the objective risk factor status of participants, the most current reported measurements for the variables of blood pressure, blood lipids and glycosylated hemoglobin were obtained from the participant's usual medical attendants. To ascertain the participant's subjective perceptions of their risk factor status, participants completed a self-administered mail-out questionnaire. RESULTS: A high level of post-operative risk factor monitoring was demonstrated. Post-operative risk factor control was not as commendable. There was a significant discrepancy identified between patient perceptions of current post-operative risk factor status and the objective reality of current post-operative risk factor status. There was a moderate positive linear correlation between level of accurate patient insight into their disease (including their post-operative risk factor control) and the level of postoperative risk factor control being achieved (r = 0.51, P <0.001). CONCLUSION: Future strategy targeted at achieving optimal post CEA and carotid angioplasty with adjuvant stenting risk factor control should consider incorporating themes that increase the level of accurate patient insight into their disease (particularly their post-operative risk factor control), for instance, patient education and effective doctor-patient communication. PMID- 22295408 TI - A combined approach to the excision of sciatic notch dumb-bell tumours. PMID- 22295409 TI - Traumatic avulsion of left common carotid and vertebral artery. PMID- 22295410 TI - The omega - Omega - variant designs (types A and B) of the keystone perforator island flap. PMID- 22295411 TI - Yin-Yang flaps: the mathematics of two keystone island flaps for reconstructing increasingly large defects. PMID- 22295412 TI - Lymphoepithelioma-like cholangiocarcinoma not associated with Epstein-Barr virus. PMID- 22295413 TI - Twin-stoma gastrostomy. PMID- 22295414 TI - Tailgut cyst. PMID- 22295415 TI - Chronic amputation stump sinus secondary to bone wax. PMID- 22295416 TI - Giant ureteric calculus. PMID- 22295417 TI - Endoscopic removal of a giant oesophageal polyp. PMID- 22295418 TI - Using bilateral iliac branch devices for endovascular iliac aneurysm repair. AB - INTRODUCTION: The endovascular repair of bilateral iliac aneurysms using bilateral Iliac Branch Devices (IBDs) has been infrequently performed and reported.We aim to describe this technique and report on the results of our case series. METHODS: Three different device designs are available. The procedural options include a totally transfemoral approach, or a combined transfemoral and brachial approach. Clinical records for patients who have had this procedure were reviewed. RESULTS: The indications for the technique include bilateral common iliac artery aneurysm repair, with or without concomitant abdominal aortic aneurysm repair. Considerations include the timing of main body endovascular aortic aneurysm repair (EVAR) device introduction, the use of a proximal access site and the type of IIA stent-graft that is used. Between 2007 and 2010, six patients had bilateral IBD implantation. All patients required an EVAR main body device in addition to bilateral IBDs. Eighty-three per cent were males, mean age was 73 years. Mean follow up was 15 months. Technical success was obtained in 100% of cases. There was one branch occlusion (8.3%). There were no type I endoleaks. One patient had a type II endoleak. CONCLUSIONS: Bilateral IBDs can be used safely and with excellent rates of technical success and branch patency in appropriately selected patients. PMID- 22295419 TI - Spontaneous superficial femoral artery giant false aneurysm. PMID- 22295420 TI - Catlin marks in an adult: an accidental discovery. PMID- 22295421 TI - Use of porcine small intestine submucosa prostheses in contaminated hernia repair. PMID- 22295422 TI - Colonic explosion by electronic cautery during living donor liver transplantation. PMID- 22295424 TI - A novel approach for conservative management of hernia mesh infection. PMID- 22295425 TI - [Peasant migration and urban social problems in modern China]. PMID- 22295426 TI - Predictors of creatinine rise post-endovascular abdominal aortic aneurysm repair. AB - BACKGROUND: Endovascular abdominal aortic aneurysm repair involves manipulation of the aorta around the renal arteries. Fenestrated grafts involve the direct cannulation, stenting and injecting of contrast into the renal arteries. These procedures may be associated with an acute post-operative creatinine rise. METHODS: We retrospectively examined data from all endovascular aortic repairs at our institution from 2005 to 2009, where contrast dosage had been recorded. Renal impairment was defined as a 25% increase in creatinine during the 5-day postoperative period. Univariable analysis was undertaken for a number of likely predictors, including: age, contrast dosage, preoperative creatinine, graft type (fenestrated or standard), diabetes mellitus, hypertension, hypercholesterolaemia, ischaemic heart disease, aspirin therapy, statins therapy, non-steroidal anti-inflammatory drug use, preoperative N-acetyl-cysteine and intravenous pre-hydration. Multivariable analysis was then applied to variables with a univariable P-value of < 0.05. RESULTS: We identified 106 consecutive cases, with complete data for 102. Twenty per cent of patients developed renal impairment (22/102). Contrast dose (P = 0.043) and fenestrated grafts (P = 0.006) were identified as significant risk factors for post-operative creatinine increase (P = 0.043). Multivariable analysis demonstrated that fenestrated grafts were a risk factor independent of contrast dosage (P < 0.05). CONCLUSIONS: Patients who received a fenestration graft (P < 0.01) and increased contrast dose (P < 0.05) were at a significant increased risk of a 25% post-operative creatinine rise. The risk of fenestration grafts persisted when multivariable regression was performed to control for contrast dosage (P < 0.05). Other variables investigated were not found to be significant in this study. PMID- 22295427 TI - [Exploring research on the history of contraband drugs and anti-drug interdiction in China: a review of some recent literature]. PMID- 22295428 TI - [The evolution of the village system of social education during the late Qing era]. PMID- 22295429 TI - Soft tissue metastases in oesophago-gastric cancer: importance of a detailed history. PMID- 22295430 TI - Eric Williams' Inward Hunger: the Caribbean as a microcosm of world history. PMID- 22295431 TI - Sudden death associated with spontaneous cerebrospinal fluid leak: a case report. PMID- 22295432 TI - [Mucosal immune systems--frontline of the biological defence mechanism]. PMID- 22295433 TI - [Surgical procedure in auditory brain stem implant]. PMID- 22295434 TI - [Prevention of secondary tuberculosis in the contact tracing]. PMID- 22295435 TI - Standing out. PMID- 22295436 TI - On the road: Florida nursing facilities rise above challenging times. PMID- 22295437 TI - State makes universal transfer form mandatory. PMID- 22295438 TI - Case management insider. A further look into case management roles, functions, models, and case loads. PMID- 22295439 TI - Case management insider. The state-of-the-art in CM models. PMID- 22295441 TI - [The fight against non transmittable diseases: a historical commitment of the World Health Organization]. PMID- 22295440 TI - [Nicole Ricard: vision, rigor and action]. PMID- 22295442 TI - [Mental health: family relations]. PMID- 22295443 TI - [Against the everyday acceptance of suicide]. PMID- 22295444 TI - [Myths and realities: continuing education standards]. PMID- 22295445 TI - [Another testimony amidst schools]. PMID- 22295447 TI - [Trembling and alimentation]. PMID- 22295448 TI - [Attention deficit with or without hyperactivity disorder: evaluation and drug therapy]. PMID- 22295449 TI - [Chimney fires: the impact of burning wood on health]. PMID- 22295450 TI - [Shedding some light on seasonal depression]. PMID- 22295451 TI - [Following the growth curve: using the new growth curves of the World Health Organization. An essential tool for pediatrics]. PMID- 22295452 TI - [Preparing for the future: teaching to help the future generations of nurses to become better]. PMID- 22295453 TI - [Management of immobilization in the elderly. A program of mobility and walking adapted for the elderly in the Cite-de-la-Sante of Laval]. PMID- 22295454 TI - [Montreal/Laval: an online program to support caregivers]. PMID- 22295455 TI - [The OIIQ implements a professional standard: to facilitate the continuing education of nurses]. PMID- 22295456 TI - [Sexuality, sports and travel: some ideas to help stoma patients to challenge themselves with the activities that confront them]. PMID- 22295457 TI - [Nursing documentation: do you know the abbreviations and symbols?]. PMID- 22295458 TI - [Death with dignity: how to react to a patient request]. PMID- 22295459 TI - [Commotio cordis: when a sport turns into a nightmare]. PMID- 22295460 TI - [Victrelis and Incivek against hepatitis C: some promising options]. PMID- 22295461 TI - [Seasonal H1N1: a worry on the competence, attitude and practices of nurses during the vaccination campaign]. PMID- 22295462 TI - [Wrong site surgery: oops! Sorry!]. PMID- 22295463 TI - [Partner notification: the cornerstone in the prevention of sexually transmitted diseases]. PMID- 22295464 TI - [Couples and money: attention! What are the traps to avoid? ]. PMID- 22295465 TI - Pigg-o-what? PMID- 22295466 TI - Importance of certified and qualified personnel for managing PACS. PMID- 22295467 TI - Developing technologies to specific clinical aims requires rigorous clinical investigation. PMID- 22295468 TI - The quest for a "winning" breast center. AB - This article focuses on the initiatives and first hand experiences in the establishment of a women's breast center at a not-for-profit, 305 bed, community hospital located in the highly affluent area of southern Connecticut. According to the National Consortium of Breast Centers (NCBC), a breast center organizes the screening, diagnosis, and treatment of breast services in a multidisciplinary approach. The services can be under one roof or at different locations, but the key is they must be under one unified leadership. Making a commitment to establish and maintain a viable breast center can be financially advantageous, as well as an outstanding service dedicated to women's breast health. PMID- 22295469 TI - Employee engagement and retention through education. PMID- 22295470 TI - Rethinking traditional staffing models. AB - The department of radiology at North Shore University Hospital in Manhasset, NY redesigned its CT technical staffing model utilizing a data driven shift optimization approach to more effectively align workload with existing technical personnel resources. Using RIS data in a pivot table format, workload patterns were evaluated by day of the week and by hour of the day, which allowed realignment of staff to meet workload demands. Sharing data with staff became a powerful driver for staff buy-in and the willingness to implement changes with staff assignments. Morale also improved when staff recognized the benefit of improved staffing levels during peak volume periods. The redesign significantly reduced wait times for inpatient CT studies, contributed favorably in reducing length of stay,and improved patient safety. PMID- 22295471 TI - I see new codes a-comin'... AB - These coding changes are the tip of the iceberg. We are still awaiting the final guidance on proper assignment of these codes as well as the new HCPCS changes for 2011. Next year certainly has a lot in store for coding and reimbursement changes. The January/February issue of Radiology Management will discuss the HCPCS Level II code changes as well as the reimbursement changes for 2011. It is definitely going to be another exciting year in the world of coding and reimbursement! PMID- 22295472 TI - Competitive edge: the art and science of branding. AB - Branding is the equivalent of building a reputation and managing the brand and brand perceptions with actions. Create and craft a desirable brand by associating brand with a personality. This is important because it relies on the collective experiences a customer has with the brand and is one of the most straightforward ways to craft a brand. Building and maintaining brand strategy is an ongoing process that must be managed. Effort must be continually made to increase the brand's perceived value to referrers and patients, to differentiate the brand from competition, to make and keep brand promises, and to create customer loyalty. PMID- 22295473 TI - Managing patient safety through NPSGs and employee performance. AB - Patient safety can only exist in a culture of patient safety, which implies it is a value perceived by all. Culture predicts safety outcomes and leadership predicts the culture. Leaders are obligated to continually mitigate hazard and take action consciously. Healthcare workers should focus on preventing and reporting mistakes with the National Patient Safety Goals (NPSGs) in mind. These include: accuracy of patient identification, effectiveness of communication among caregivers, improving safety of medications, reducing infections, reducing risk of falls, and encouraging patients to be involved in care. Poor performers and reckless behavior need to be mitigated. If employees recognize their roles in the process, feel empowered,and have appropriate tools, resources,and data to implement solutions, errors can be avoided and patient safety becomes paramount. PMID- 22295474 TI - Critical success factors: innovation. PMID- 22295475 TI - Building a culture of excellence does not equal perfection. PMID- 22295476 TI - Health savings accounts and health reimbursement arrangements: assets, account balances, and rollovers, 2006-2011. AB - ASSET LEVELS GROWING: In 2011, there was $12.4 billion in health savings accounts (HSAs) and health reimbursement arrangements (HRAs), spread across 8.4 million accounts, according to data from the 2011 EBRI/MGA Consumer Engagement in Health Care Survey, sponsored by EBRI and Matthew Greenwald & Associates. This is up from 2006, when there were 1.3 million accounts with $873.4 million in assets, and 2010, when 5.4 million accounts held $7.3 billion in assets. AFTER LEVELING OFF, AVERAGE ACCOUNT BALANCES INCREASED: After average account balances leveled off in 2008 and 2009, and fell slightly in 2010, they increased in 2011. In 2006, account balances averaged $696. They increased to $1,320 in 2007, a 90 percent increase. Account balances averaged $1,356 in 2008 and $1,419 in 2009, 3 percent and 5 percent increases, respectively. In 2010, average account balances fell to $1,355, down 4.5 percent from the previous year. In 2011, average account balances increased to $1,470, a 9 percent increase from 2010. TOTAL AND AVERAGE ROLLOVERS INCREASE: After declining to $1,029 in 2010, average rollover amounts increased to $1,208 in 2011. Total assets being rolled over increased as well: $6.7 billion was rolled over in 2011, up from $3.7 billion in 2010. The percentage of individuals without a rollover remained at 13 percent in 2011. HEALTHY BEHAVIOR DOES NOT MEAN HIGHER ACCOUNT BALANCES AND HIGHER ROLLOVERS: Individuals who smoke have more money in their accounts than those who do not smoke. In contrast, obese individuals have less money in their account than the nonobese. There is very little difference in account balances by level of exercise. Very small differences were found in account balances and rollover amounts between individuals who used cost or quality information, compared with those who did not use such information. However, next to no relationship was found between either account balance or rollover amounts and various cost conscious behaviors. When a difference was found, those exhibiting the cost conscious behavior were found to have lower account balances and rollover amounts. DIFFERENCES IN ACCOUNT BALANCES: Men have higher account balances than women, older individuals have higher account balances than younger ones, account balances increase with household income, and education has a significant impact on account balances independent of income and other variables. DIFFERENCES IN ROLLOVER AMOUNTS: Men rolled over more money than women, and older individuals had higher rollover amounts than younger individuals. Rollover amounts increase with household income and education, and individuals with single coverage rolled over a slightly higher amount than those with family coverage. PMID- 22295477 TI - [Therapy of the distal fractures of radius: choices and thoughts]. PMID- 22295478 TI - [A case control study on the treatment of distal radioulnar joint instability combined with distal radius fractures between fixation and non-fixation distal radioulnar joint]. AB - OBJECTIVE: To explore the options on treatment of distal radioulnar joint instability combined with distal radius fracture. METHODS: From June 2007 to December 2009, 264 patients with unstable distal radius fractures were treated with open reduction and internal fixation, in which 42 patients combined with distal radioulnar instability. Distal radioulnar joints of 20 patients were fixed with Kirschner wire or plaster cast at supinator position, and other distal radioulnar joints of 22 patients were not fixed. Range of motion of wrist joints and grip strength were observed; function of wrist were evaluated by modified Gartland-Werley scoring system (GW score); stability of distal radioulnar joints were tested at final follow-up. RESULTS: Forty-one patients were followed up more than 1 year. All fractures obtained healing within 3 months after operation, and apposition of joints was good, no significant subluxation or dislocation were found. There were not statistical differences in grip strength, motion of joints and GW score between two groups (fixation and non-fixation). Only one patient occurred chronic distal radioulnar instability. CONCLUSION: There was no significant difference between fixation and non fixation for the treatment of distal radius fractures with distal radioulnar joint instability. For this reason, if fractures can be satisfactory reduced, there is no need for the one stage distal radioulnar joint fixation. PMID- 22295479 TI - [A case control study on the treatment of unstable distal radius fractures with internal and external fixation]. AB - OBJECTIVE: To explore the clinical effects of diaplastic external fixator on the treatment of unstable fractures of distal radius. METHODS: A clinical data of 60 patients with unstable fractures of distal radius admitted to Wangjing Hospital from August 2005 to September 2009 were retrospectively analyzed with the paired design. According to the paired design, 60 patients were equally divided into two groups (internal fixation group and external fixation group), which were respectively treated with open reduction and steel plate internal fixation (internal fixation group) or closed reduction and external fixation (external fixation group), including 8 males and 52 females, with an average age of 60.27 years ranging from 34 to 85 years. Left side was in 33 cases and right side was in 27 cases. All fractures were closed and caused by hand supporting when falling down. According to AO classification, type A3 was in 22 cases, type B2 was in 4 cases, type B3 was in 2 cases, type C1 was in 20 cases, type C2 was in 8 cases, type C3 was in 4 cases. Palmar flexion, dorsiflexion, radial deviation, ulnar deviation, pronation, supination, grip strength, radial angle, radial length, volar tilt were observed before and after operation. RESULTS: All the patients were followed up from 12 to 18 months with an average of 15.4 months. The radial length was (4.85 +/- 2.75) mm,volar tilt (14.66 +/- 10.77) degrees, radial angle (7.90 +/- 4.70) degrees in the external fixation group,while those were (4.29 +/- 1.53) mm, (14.39 +/- 5.01) degrees, (6.19 +/- 3.15) degrees in the internal fixation group, but with no statistical significance (P>0.05). Function comparison of internal and external fixation group, P-value of every function is more than 0.05 or equal to 0.05, with no statistical significance except for supination and radial deviation. The functions of wrist joints were evaluated according to Batra scoring system at 1 year after operation. The average radiological scores of external fixation group was 86.27,in which 15 cases were excellent, 11 good, 1 fair,3 poor,while the average functional scores was 94.93, and all the cases were excellent. The average radiological scores of internal fixation group was 91.27, 16 cases were excellent, 12 good, 2 fair, while the average functional scores was 94.23, in which all the cases were excellent. CONCLUSION: Compared with the open reduction and steel plate fixation, the unstable fractures of distal radius treating by diaplastic external fixator can be achieved a similar result, with no statistical significance. PMID- 22295480 TI - [Case-control study on the clinical characteristics of senile-osteoporotic Colles fracture]. AB - OBJECTIVE: To analysis and compare the clinical characteristics of Colles fractures between patients with osteoporotic and without osteoporotic. METHODS: From June 2007 to June 2009, 260 patients with Colles fracture were reviewed, including 60 males and 200 females, with a mean age of 66.5 years old. According to Cooney classification: 44 patients were type I, 83 patients were type II, 92 patients were type III and 41 patients were type IV. Among the patients, 96 patients were osteoporotic Colles fractures, and 164 patients without osteoporotic. The general information, invalidiation rate and short-term clinical results were compared between two groups. RESULTS: There were no statistically difference of age, gender and fracture position between the two groups. There were more patients with type III and type IV, and higher invalidiation rate in osteoporotic Colles fracture group compared to those of no osteoporotic Colles fracture group (P<0.01). At the 6 months after treatment, the clinical effects of no osteoporotic Colles fracture group was better than that of osteoporotic Colles fracture group (P<0.01). CONCLUSION: The senile-osteoporotic Colles fracture has different clinical characteristics, which should be given special treatment, frequent review and communication between doctors and patients during the period of treatment. PMID- 22295481 TI - [Analysis of therapeutic effects of external fixator for the treatment of comminuted fracture of distal radius]. AB - OBJECTIVE: To evaluate the clinical effects of external fixator in treating comminuted fracture of distal radius. METHODS: From Mar.2008 to Dec.2009, 37 patients with comminuted fracture of distal radius were treated with external fixator or assisted with Kirschner wire and T-shape locking compression plate (T LCP) fixation. There were 14 males and 23 females, ranging in age from 30 to 79 years, with an average of 59.1 years. According to AO typing, type C1 was in 3 cases, type C2 was in 11 cases and type C3 was in 23 cases. Function of wrist joint and X-ray films were observed according to Gratland-Werley system at different months. RESULTS: All patients were followed up from 8 to 24 months with an average of 12 months. All fractures had healing with an average time of 8 weeks. According to Gratland-Werley system, 16 cases obtained excellent result, 17 good, 4 fair, the rate of excellent and good was 89.0%. CONCLUSION: External fixator can obtained satisfactory clinical effect in treating comminuted fracture of distal radius. PMID- 22295482 TI - [The combined fixation with splints and plaster after closed reduction for the treatment of distal fractures of radius in elderly patients]. AB - OBJECTIVE: To evaluate the effects of combined fixation with splints and plaster after closed reduction for the treatment of distal fractures of radius in elderly patients METHODS: From January 2009 to January 2011, 122 patients with distal fractures of radius were treated by the united fixation with splints and plaster after closed reduction. There were 43 males and 79 females, ranging in age from 60 to 86 years with an average of 74 years. Among the patients, traffic accident injury was in 12 cases and fall injury was in 109 cases; all fractures were closed, the time form injury to visit was for 30 min to 7 days. The X-rays, wrist pain, functional status, range of motion and grasp force of patients were observed at follow-up. Cooney modified Green-O'Brien standard was used to evaluate the clinical effects. RESULTS: All the patients were followed up from 3 months to 2 years with an average of 15.4 months. Re-displacement occurred in 8 cases (including 4 cases radial displacement, 3 cases dorsal displacement, 1 case palmaris displacement) and re-reduction occurred in 4 cases, surgical treatment was in 2 cases, refused to reset or surgical treatment in 2 cases. Radial shorten in 13 cases middle-later period. All fractures obtained healed. According to the Green-O'Brien standard, 46 cases got excellent results, 65 good, 6 fair, and 5 poor. CONCLUSION: The combined fixation with splints and plaster after closed reduction is a effective method in treatment of distal fractures of radius in elderly patients, which can more overcome redisplacement of distal fractures of radius, recover function of wrist joint. PMID- 22295483 TI - [Manipulative reduction and external fixation with cardboard for the treatment of distal radial fracture]. PMID- 22295484 TI - [Bone setting manipulation and splint fixation for the treatment of Colles fracture in 78 patients]. PMID- 22295485 TI - [Case-control study on the relationship between body mass index and lower limb alignment of patients with knee osteoarthritis]. AB - OBJECTIVE: To investigate the relationship between body mass index and lower limb alignment of patients with knee osteoarthritis. METHODS: From July 2008 to June 2010, 78 patients who suffered from severe knee osteoarthritis were treated with total knee replacement, including 17 males and 61 females, ranging from 41 to 85 years old, with an average age of 68.1 years. The Chinese average adult body mass index (BMI) classification standard was used to classify the patients into three groups: normal group, BMI<24.0, including 3 males and 11 females, totalized 14 patients (28 knees), with the mean age of (69.5 +/- 4.7); overweight group, 24.0 < or = BMI<28.0, including 4 males and 25 females, totalized 29 patients (58 knees), with the mean age of (66.4 +/- 7.9) years; and obese group, BMI > or = 28.0, including 10 males and 25 females, totalized 35 patients(70 knees), with the mean age of (69.1 +/- 8.3) years. The limb X-ray film measuring system was used to measure the lower limb alignment at the supine and weight-bearing position. RESULTS: There were no statistical significances between the normal group and the overweight group in the knee varus angle at the supine and weight bearing position (P>0.05). However, keen varus angle of the overweight group increased compared with the other two groups at the supine position,and the angle of the weight-bearing position increased nearly 2 degrees, but no statistical significance. There was no statistical significance between supine and weight bearing position in the three groups of BMI, but the knee varus angle at the supine position was more than the weight -bearing position in the three groups. CONCLUSION: The knee varus angle of obese patients with osteoarthritis in the weight-bearing position increases obviously. It indicates that obesity is an important factor increasing the angle of lower limb alignment. PMID- 22295486 TI - [Case-control study on Hennipen external rotation procedure for reduction of 28 patients with acute anterior shoulder dislocation]. AB - OBJECTIVE: To introduce the characteristics and its clinical effects of Hennipen external rotation procedure for reduction of acute anterior shoulder dislocation. METHODS: From March 2007 to March 2010, 72 patients with acute anterior shoulder dislocation were treated with manipulative reduction in our department. All the patients were divided into two groups: the Hippocratic group with 44 patients receiving regular Hippocratic procedure, and the Hennipen group with 28 patients receiving Hennipen external rotation procedure. Clinical manifestation and radiology were used to diagnose. After reduction procedures, external fixation was applied for another 3 to 4 weeks. The reduction course, complication and function recovery at follow-up were recorded and compared. The student test was used to analyze the difference between groups. RESULTS: Thirty-two patients in the Hippocratic group and 3 in Hennipen received intravenous anesthesia. Manipulation time of the Hippocratic group ranged from 2 to 5 minutes with a mean of (3.9 +/- 1.2) minutes, obviously different from that of Hennipen,which ranged from 0.5 to 2 minutes with a mean of (1.3 +/- 0.7) minutes. Complications occurred in 2 cases of the Hippocratic group and none of the Hennipen group. The UCLA scores of shoulder joint at follow-up were 34.2 +/- 2.1 and 33.8 +/- 1.0 respectively in two groups, with no significant difference. CONCLUSION: Compared with Hippocratic procedure, Hennipen external rotation procedure is easier to manipulate, bring less complications and the same effect. It is worth further clinical applications. PMID- 22295487 TI - [Analysis on morbidity factor of bilateral intertrochanteric fractures]. AB - OBJECTIVE: To study the morbidity factors of bilateral intertrochanteric fractures by analyzing medical records, so as to provide evidences for preventing the multiple intertrochanteric fractures. METHODS: From Janurary 2000 to June 2009, 68 patients with bilateral intertrochanteric fractures were studied, including 31 males and 37 females, ranging in age from 42 to 95 years with an average age of 75 years. There were type A1 in 24 hips, type A2 in 96 hips, and type B3 in 16 hips. One hundred and twenty-eight hips had received surgical treatment, 8 hips were treated with conservative method. On the first injury, 67 patients discharged after treatment, 1 patients discharged after treatment in other department. On the second injury, 58 patients discharged after treatment, 2 patients died of complications, 8 patients dischagred after treatment in other department. The risk factors including age, cause of injury, fractures type, complications, osteoporosis and treatment were analyzed. RESULTS: The average age of two fractures were (73.6 +/- 9.25) and (76.7 +/- 6.74) years; the major injury cause was fall; the A2-type fractures went up to 80.88% on the secondary injury;and the proportion of complications was high, mainly geriatric cognitive disorders, hemiplegic paralysis, and dysopia. Bone mineral density measurement of 16 cases showed marked osteoporosis. CONCLUSION: Osteoporosis and fall injury contribute mostly to the multiple intertrochanteric fractures. Complication was the dominating risk factor. Treatment of osteoporosis, intensive care, postoperative rehabilitation and effective initial surgery are the key to prevent the secondary intertrochanteric fractures in old people. PMID- 22295488 TI - [Effective analysis of open reduction and internal fixation for the treatment of acute Lisfranc joint injury]. AB - OBJECTIVES: A retrospective study was used to evaluate the short to intermediate outcomes of open reduction and internal fixation of acute Lisfranc joint injuries. METHODS: From January 2003 to December 2009, 47 patients with Lisfranc injuries were treated in the study,41 patients were analyzed in current study with an average age of thirty-one years old. All of patients were treated with open reduction and internal fixation. According to the Myerson classification system, there were 9 type-A fractures, 7 type-B1, 11 type-B2, 10 type-C1, 5 type C2. The AOFAS scale and VAS scale were used for the outcome measurement at the final follow-up. RESULTS: There were 41 patients with 42 operations were followed up and with a mean time of 36 months (ranged, 12 to 71 months). The mean AOFAS score was (84.2 +/- 2.8) points (ranged, 65 to 100 points), with an excellent and good rate of 81 percent. The mean VAS score was (2.6 +/- 0.5) points (ranged, 0 to 6 points). Three patients developed superficial infection, and two developed skin necrosis. Nineteen patients had weight-bearing or walking pain. All of the patients had radiographic evidence of degenerative change, four with malunion of the second tarsometatarsal joint, and two of the patients with hallux valgus deformity change. CONCLUSION: According to the results of the study, anatomic reduction and internal fixation can get the satisfactory results for the treatment of acute Lisfranc injuries during a short to intermediate follow-up time. All of the patients would have different degree of tarsometatarsal joint degenerative changes, but these changes are non-progressive and associated with minimal loss of function. PMID- 22295489 TI - [Case-control study on manipulation combined with Chinese herbs for the treatment of lumbar disc herniation within chronic stage]. AB - OBJECTIVE: To observe and compare the therapeutic effects of two methods to lumbar disc herniation treated by manipulation combined with Chinese herbs and traction with Western medicine. METHODS: A multi-center with a central district unit was used to study the patients with lumbar disc herniation from November 28th, 2008 to May 7th, 2010. All the patients were divided into treatment group and control group. The treatment group had 100 cases, including 45 males and 55 females, averaged (43.43 +/- 9.18) years. The treatment group was treated by manipulation combined with Chinese herbs; Control group had 100 cases (5 cases were fall off), including 38 males and 57 females, averaged (42.29 +/- 9.78) years. The control group was treated by traction with Western medicine. The course of treatment was 3 weeks. VAS, M-JOA, LMS (lower limb muscle strength) and classification efficacy was used to evaluate outcome and therapeutic effects before and after treatment. RESULTS: VAS and M-JOA were improved after the treatment both in treatment group and control group; there was no significant difference in LMS before and after treatment in both groups. VAS and M-JOA in treatment group was superior to those of control group after treatment. There was no significant difference in LMS. According to classification efficacy, 41 cases got excellent result, 34 good, 13 fair and 12 poor in treatment group; in control group, 35 cases obtained excellent results, 16 good, 19 fair and 25 poor. The effect of treatment group was better than that of control group. CONCLUSION: Both of two methods can improve the score of VAS, M-JOA, and treatment group is better than that of control group. While for the improvement of LMS, both of two methods have no obvious effects. PMID- 22295490 TI - [The cup safe-zone and optimum combination of the acetabular and femoral anteversions that fulfills the desired range of motion of the hip]. AB - OBJECTIVE: To investigate safe range of acetabular prosthesis angle and the optimum combination of cup and neck in the range of activities of daily living (ADL). METHODS: A three-dimensional generic parametric and kinematic simulation module of THA was developed. Range of motion (ROM) of flexion > or = 110 degrees, internal-rotation > or = 30 degrees at 90 degrees flexion, extension > or = 30 degrees and external rotation > or = 40 degrees were defined as the normal criteria for desired ROM for activities of daily living (ADL), and ROM of flexion > or = 120 degrees, internal-rotation > or = 45 degrees at 90 degrees flexion, extension > or = 30 degrees and external rotation > or = 40 degrees as the severe criteria. The range of the changes in the general head-neck ratios (GR), the femoral neck anteversion (FA), the operative anteversion (OA) and operative inclination (OI) of the cup component were 2-2.92, 0 degrees-30 degrees, 0 degrees-70 degrees, 10 degrees-60 degrees respectively. For the collodiaphyseal angle (CCD) of 135 degrees, the corresponding OA related to the OI which every 5 degrees was calculated, and described using dots and lines in a coordinate system in which OI of acetabular cup was the horizontal ordinate and OA of acetabular cup was the vertical ordinate. All data was analyzed by SAS 6.12 software. RESULTS: Large GR greatly increased the size of safe range and it was recommended that GR be more than 2.37 when the CCD-angle was 135 degrees as it further increases the size of safezone. The size of cup safety range of the severe criteria was smaller than normal criteria. When the CCD-angle was 135 degrees, the optimum relationship between OA of acetabular and FA of the normal criteria and the severe criteria can be estimated by the formula: Y1=-0.816X1 + 39.76 (R2=0.993), Y2=-0.873X2 + 47.04 (R2=0.999) respectively. CONCLUSION: Large GR greatly increases the size of safe-zone and it is recommended that GR be more than 2.37, so it extends the acceptable range of error that clinicians cannot avoid it completely. The larger range of the hip motion, the smaller size of the cup safe-zone,but can retrieve by increase the GR. The OA is negative with FA. PMID- 22295491 TI - [Effects of nicotine on bone marrow stromal cells proliferation and differentiation of chondrocyte in vitro]. AB - OBJECTIVE: To examine the effects of various concentration of nicotine on bone marrow stromal cells (BMSCs) proliferation and differentiation of cartilaginous in vitro. METHODS: BMSCs was obtained from femoral bone and tibia of New-Zealand albino rabbit. The cells of the 3rd generation were used in study. Different concentration of nicotine (0, 1 x 10(-7), 1 x 10(-6), 1 x 10(-5) M) were added into BMSCs. BMSCs proliferation was analyzed by MTT assay at the 1, 4, 7, 14 days. The expression of collagen type II and aggrecan as the marker genes of cartilaginous differentiation from BMSCs were detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Microscope showed that BMSCs transformed from round to fusiform shape. The concentration of nicotine in 1 x 10(-7), 1 x 10(-6) M had a significant positive effect on cell proliferation and the expression of type II collagen in a time-dependent manner when supplemented in commonly used induction media (P<0.05). Concentrations of nicotine in 1 x 10( 7) can promote the expression of aggrecan at the 7th day after induction,and in 1 x 10(-5) M may inhibit the expression of type II collagen and aggrecan. CONCLUSION: It was implied that local application of nicotine at an appropriate concentration may be a promising approach for enhancing cartilaginous differentiation capacity of BMSCs in cartilage tissue engineering. PMID- 22295492 TI - [Treatment of femoral neck fractures after the fixation of ipsilateral femoral shaft by antegrade intramedullary nail]. AB - OBJECTIVE: To investigate the treatment of femoral neck fractures after the fixation of ipsilateral femoral shaft fracture by antegrade intramedullary nail. METHODS: A retrospective study on 12 patients with femoral neck fractures after the fixation of ipsilateral femoral shaft fracture by antegrade intramedullary nail, which were identified intraoperatively or postoperatively from January 2000 to January 2010. All the patients were treated with 2 supplemental screws placed anteriorly and posteriorly to intramedullary nail seperately. All the patients were periodic followed-up, fractures union and functional recovery were evaluated. RESULTS: All the patients were followed up, and the duration ranged from 10 to 36 months (averaged 16.5 months). The mean healing time was 3.6 months in femoral neck fractures and 5.4 months in femoral shaft fractures. No osteonecrosis of femoral head was found. According to Harris scoring system for hip function, 7 patients got an excellent result, 3 good, 2 fair. CONCLUSION: Treatment of femoral neck after the fixation of ipsilateral femoral shaft by antegrade intramedullary nail with 2 screws placed anteriorly and posteriorly to intramedullary nail separately is feasible, and has the advantages of reliable fixation, less trauma and high rate of fracture healing. PMID- 22295493 TI - [Single factor analysis of motor dysfunction and imaging and clinical features in metastatic epidural spinal cord compression]. AB - OBJECTIVE: To explore the relationship of motor dysfunction of the lower extremities with the imaging appearances and clinical features of metastatic epidural spinal cord compression (MESCCs). METHODS: From July 2006 to December 2007, 26 successive patients with metastases of the thoracic, lumbar and the cervical spine were treated in our department. Forty-three main involved vertebra in all 26 patients were evaluated by magnetic resonance imaging and computed tomography, and were scored according motor dysfunction in this study. Fourteen patients (25 vertebrae) had motor dysfunction. RESULTS: Among 26 patients, 12 cases with visceral metastasis,in which had motor dysfunction in 10 cases; 14 cases without visceral metastasis, in which had motor dysfunction in 4 cases; comparison between two groups, P=0.0079. Among vertebral presence of continuity of 43 main involved vertebrae, 16 vertebrae had motor dysfunction;among vertebral absence of continuity, motor dysfunction occurred in 9 vertebrae, comparison between two groups, P=0.1034. Among vertebral presence of lamina involvement of 43 main involved vertebrae, 11 vertebrae had motor dysfunction; among vertebral absence of lamina involvement, motor dysfunction occurred in 14 vertebrae, comparison between two groups, P=0.020 5. Among vertebral presence of protruding of vertebral posterior wall of 43 main involved vertebrae, 12 vertebrae had motor dysfunction; among vertebral absence of protruding of vertebral posterior wall, 13 vertebrae had motor dysfunction, comparison between two groups, P=0.0334. Among vertebral presence of involvement epidural space of 43 main involved vertebrae, 11 vertebrae had motor dysfunction; among vertebral absence of involvement epidural space, 14 vertebrae had motor dysfunction, comparison between two groups, P=0.003 6. Such factors as age, gender, whether or not received regular chem before admission, back pain degree of metastasis, received regular chem before admission, therapeutic efficacy of primary tumor, number of bony metastases outside spine, number of the main involved vertebrae, level of vertebral metastases location, level of continuous involved vertebrae, vertebral body involvement, fracture of anterior column, fracture of posterior wall, and pedicle involvement had no effects on incidence of motor dysfunction due to MESCC (P>0.05). CONCLUSION: MESCC with visceral metastases, lamina involvement, presence of outstanding buttocks sign of posterior wall,involvement epidural space tended to cause symptomatic MESCC. Incidence of continuity of main involved vertebrae occurred more frequently in the CUTS compared with other levels of spine. PMID- 22295494 TI - [Vacuum sealing drainage (VSD) for the treatment of large cutaneous deficiency of inferior belly and left thigh: a case report]. PMID- 22295495 TI - [A study of proximal humerus fractures using close reduction and percutaneous minimally invasive fixation]. AB - OBJECTIVE: To investigate the clinical effects of close reduction and percutaneous minimally invasive fixation in the treatment of proximal humerus fractures. METHODS: From April 2008 to March 2010, 28 patients with proximal humerus fracture were treated with close reduction and percutaneous minimally invasive fixation. There were 21 males and 7 females, ranging in age from 22 to 78 years,with an average of 42.6 years. The mean time from suffering injuries to the operation was 1.7 d. Nineteen cases caused by falling down, 9 cases by traffic accident. The main clinical manifestation was swelling, pain and limited mobility of shoulders. According to Neer classification, two part fractures were in 17 cases and three part fractures in 11 cases. The locking proximal humerus plate was used to minimally fixation through deltoid muscle under acromion. The operating time,volume of blood loss, the length of incision and Constant-Murley assessment were applied to evaluate the therapeutic effects. RESULTS: The mean operating time was 40 min, the mean blood loss was 110 ml, and the mean length of incision was about 5.6 cm. The postoperative X-ray showed excellent reduction and the plate and screws were successfully place. Twenty-eight patients were followed up for 6 to 24 months (averaged 14.2 months). The healing time ranged from 6 to 8 weeks and all incision was primarily healed. There were no cases with necrosis head humerus, 24 cases without omalgia, and 4 cases with o-malgia occasionally. All the patients can complete the daily life. The mean score of Constant-Murley assessment was 91.0 +/- 5.8, 24 cases got an excellent result, 3 good and 1 fair. CONCLUSION: Close reduction and percutaneous minimally invasive fixation, not only can reduce surgical invasive, but also guarantee the early function activities. It has the advantages of less invasive, fixed well and less damage of blood circulation. PMID- 22295496 TI - [Treatment of chronic osteomyelitis of tibia with debridement and vacuum sealing drainage (VSD) of cavitas medullaris]. AB - OBJECTIVE: To explore the therapeutic effect of debridement and vacuum sealing drainage (VSD) of cavitas medullaris for the treatment of chronic osteomyelitis of tibia. METHODS: From March 2006 to May 2009, 19 patients with chronic osteomyelitis of tibia were treated by debridment and VSD, then the second operation were performed to close the wound. Among them, 12 patients were male and 7 patients were female, the average age was 39 years (ranged from 25 to 68 years). The course of disease were from 10 months to 5 years. The main clinical symptoms were red swelling, tenderness and fluid of local soft tissue. There were prolonged unhealed sinus and pus; the X-ray showed osteosclerosis, increased bone mineral, and sequestrum and dead space was formed. The result of bacterial culture showed 3 cases were aeruginosus bacillus, 13 cases staphylococcus aureus, 1 case bacillus aerogenes and 2 cases beta streptococcus. Among them, 3 cases were methicillin resistant staphylococcus (MRS). RESULTS: After debridement and VSD of cavitas medullaris 18-22 days later, the granulation tissue grow well and the wounds of the 19 patients all healed primarily with direct suturing of 17 cases, loco-regional flap of 2 cases. The standard of wound healing was the dryness, cleanness and no drainage. The X-ray revealed the bone tissue grew well and no relapse and fracture occurred during followed-up 6-12 months. CONCLUSION: The debridement and VSD of cavitas medullaris is a very effective and safe treatment for chronic osteomyelitis of tibia. PMID- 22295497 TI - [Treatment of thoracolumbar burst fracture with lateral anterior decompression, internal fixation with Ventrofix and bone graft with titanic mesh]. AB - OBJECTIVE: To discuss the efficacy of lateral anterior decompression, internal fixation with Ventrofix and bone graft with titanic mesh in the treatment of severe thoracolumbar burst fracture. METHODS: From January 2008 to January 2010, 21 patients with severe thoracolumbar burst fracture were treated with lateral anterior decompression, internal fixation with Ventrofix, bone graft with titanic mesh. There were 15 males and 6 females, ranging in age from 21 to 46 years with an average of 32.2 years. Segment of fracture: 3 cases were in T11, 6 cases in T12, 7 cases in L1, 5 cases in L2. The mean kyphosis angle was 20.1 degrees and loading of fracture was 7.8 scores. Twenty-one cases accompany with incomplete paralysis. Nerves functions were observed according to Frankel grade; correction and maintain of kyphosis angle were observed by X-rays and CT. RESULTS: All the patients were followed up from 12 to 34 months with an average of 18.5 years. Postoperative complication including injury of pleura in 1 case, dynamic ileus in 2 cases, ilioinguinal nerve injury in 1 case, faulty union of wound in 1 case. All the above complications got recovery after symptomatic treatment. The mean kyphosis angle in fusional segment were 4.2 degrees and the rate of correction was 79%. Nerves functions of all patients got improvement and no internal fixation fail, kyphosis angle obviously lost, titanium mesh shifting, loosening and breakage of screw were found at final follow-up. CONCLUSION: Lateral anterior decompression, bone graft with titanic mesh, internal fixation with Ventrofix is an idea technique for severe thoracolumber burst fracture, but the method can not be used for patient with severity osteoporosis. PMID- 22295498 TI - [The manipulation of turn and sway for the treatment of special kind of Galeazzi fracture in youngsters]. PMID- 22295499 TI - [Application of the self-designed cervical lateral mass anchor in single-door laminoplasty]. PMID- 22295500 TI - [Knee pushing reduction of the distal fractures of radius]. PMID- 22295501 TI - [Treatment of phalangeal fractures with external fixation by using single-use syringe]. PMID- 22295502 TI - [Manipulative reduction for the treatment of epiphyseal fracture of distal radius in children: a report of 15 cases]. PMID- 22295503 TI - [Progress of research between Helicobacter pylori infection and osteoporosis]. AB - Helicobacter pylori (HP) is an infectious pathogen which can easily infringe gastric mucosa. If the body is infected by HP, it can release cytokines, such as TNF-alpha, IL-1 and IL-6. These cytokines can regulate the absorption and transformation of bone, promote the formation of osteoclast, and then cause localized or systemic osteoporosis. HP infection may decrease the level of estrogen and vitamin B12, which is considered as a risk factor for osteoporosis. Helicobacter pylori infection is related with the occurrence of gastritis, peptic ulcer and gastric malignancies, and these diseases and treatments are associated with osteoporosis. Meanwhile the application of proton pump inhibitor (PPI) can influence absorption of calcium, decrease the level of serum calcium and increase the risk of fracture. Gastrostomy may cause bone metabolism disorders. PMID- 22295504 TI - [Research advancement of the tennis elbow]. AB - Tennis elbow is a common disease. The current research showed that the basic pathology of tennis elbow is not inflammation, but lateral elbow tendinopathy. Ultrasound image has been frequently used for diagnosis of tennis elbow, it can evaluate the condition of disease and show prognosis. Tennis elbow needs a comprehensive treatment. Most patients can obtain satisfactory effects by non operation, especially the application of the Sodium hyaluronate, autologous blood and botulinum toxin. The principle of operation is to clear the common extensor tendon and repair or rebuild the tendon dead centre if necessarily. The arthroscopic surgery has the advantages of less invasion, rapid recovery,and become the new chioce for the treatment of tennis elbow. Both open operation and arthroscopic surgery can obtain good effects. PMID- 22295505 TI - [Study on differentiation of rat adipose tissue-derived stromal cells into Schwann-like cells]. AB - OBJECTIVE: To investigate the phenotypic, molecular and biological characteristics of adipose tissue-derived stromal cells (ADSCs) differentiated alonely a Schwann cells (SCs) lineage and to provide a new cells' seed source for nerve tissue engineering or cell therapy. METHODS: Cultured ADSCs were isolated from SD rats and the undifferentiated ADSCs were confirmed by detection of MSC specific cell-surface markers. The ADSCs were differentiated along a glial cell lineage using an established cocktail of growth factors. Following differention, we used immunofluorescene staining and RT-PCR to evaluate the characteristics of differentiated WJMSCs. RESULTS: ADSCs were successfully isolated from the rats' fat tissue. The isolated ADSCs expressed CD29, CD90 but not CD34, CD44 nor CD45. Osteogenic differentiation was detected by Alizarin red staining and adipogenic differentiation was comfirmed by Oil-red O staining. ADSCs treated with a mixture of glial growth factors adopted a spindle-like morphology similar to Schwann cells. Immunocytochemical staining and RT-PCR analysis revealed that the treated cells expressed the glial markers S100, P75 and glial fibrillary acidic protein indicative of differentiation. CONCLUSION: ADSCs can be differentiated into cells that are Schwann-like in terms of morphologic features and phenotype and could be suitable Schwann-cell substitutes for nerve repair in clinical applications. PMID- 22295506 TI - [Effect of neuropepide Y on food intake using an improved intracerebroventricular administration in domestic chicken]. PMID- 22295507 TI - [miRNA expression change of differentiation of mice marrow mesenchymal stem cells into adipocytes]. AB - OBJECTIVE: To explore miRNA expression change of differentiation of mice marrow mesenchymal stem cells (MSCs) into adipocytes, which lay the foundation for further studies on molecular mechanism of miRNA regulating the differentiation of MSCs into adipocytes. METHODS: C57BL/6 mice MSCs were isolated, cultured through the whole bone marrow method, amplified by the differential adherent method. Cell growth was observed by morphology and the expression of superficial antigen CD29, CD44, CD34 were detected through immunohistochemistry. MSCs was induced to differentiation into adipocytes with adipocyte differentiation medium, and adipogenic differentiation of MSCs was analyzed by oil Red O staining. MicroRNA microarray was used to investigate the differentially expressed miRNAs in MSCs and adipocytes. RESULTS: (1) The fifth passage of MSCs had high purity under an inverted m icroscope. Immunohistochemistry staining showed that CD29, CD44 were positive and CD34 was negative in more than 90% MSCs. There were a large number of lipid droplets in cytoplasm after MSCs were induced with adipocyte differentiation medium, Oil O staining was positive. (2) The microarray experiment showed that 75 differentially expressed miRNAs were obtained in adipocytes compared with MSCs, 20 up-regulated and 55 down-regulated miRNAs were observed among them. CONCLUSION: There was a expression change of miRNA of differentiation of MSCs into adipocytes, some miRNAs might play important roles in MSCs adipogenic differentiation. PMID- 22295508 TI - [Effects of Tongxinluo on neuron ultrastructure and endothelial cell self repairing ability in hypoxia preconditioning mice]. AB - OBJECTIVE: To observe the ultrastructure changes of cerebral cortex neuron and endothelial cell in hypoxia preconditioning mice and the effects of Tongxinluo (TXL, Chinese traditional medilihe) on them. METHODS: Mice were randomly divided into 4 groups: control group, hypoxia group, hypoxia preconditioning (HP) group and Tongxinluo (TXL) group. The hypoxia preconditioning mice were exposed by repetitive hypoxia for 5 runs. The animal's tolerance time of each hypoxia run was recorded. The ultrastructure change of cerebral neuron and endothelial cell were studied by electron microscope. RESULTS: The hypoxic tolerance time in HP and TXL groups were significantly increased run by run. Compared with HP group, the tolerance time of TXL group were increased in every run. The ultrastructure of cerebral neuron and endothelial cell in hypoxia group changed obviously, mitochondrion and endoplasmic reticulum destroyed. However they were slighter in HP group than those in hypoxia group. The change in TXL group had no obvious differentce with control group and were slighter than those in HP group. CONCLUSION: Hypoxia preconditioning shows that organism has a strong self repairing ability. Tongxinluo self-repairing; could increase self-repairing ability and adaptive ability of mice to hypoxia obviously. PMID- 22295509 TI - [Immunohistochemical study on the expression of caspase, bax, bcl-2 and c-kit after SCI in Bufo bufogargarizan]. PMID- 22295510 TI - [The role of extracellular signal-regulated kinase in induction of apoptosis with salvia miltiorrhiza monomer IH764-3 in hepatic stellate cells]. AB - OBJECTIVE: To explore the effect of Salvia miltiorrhiza monomer IH764-3 on apoptosis in hydrogen peroxide (H2O2)-stimulated hepatic stellate cells (HSCs). METHODS: HSCs were cultured in medium with different IH764-3 doses (10 mg/L, 20 mg/L, 30 mg/L, 40 mg/L) and without IH764-3. Direct cell count, 3H-thymidine incorporation, Annexin-V/Propidium Iodide double-labeled flow cytometry, TUNEL and transmission electron microscopy were employed to estimate the influence of IH764-3 on proliferation and apoptosis of HSCs. The expression of extracellular signal-regulated kinase 1 (ERK1) mRNA and protein in HSCs were detected using RT PCR and Western blot respectively. RESULTS: It was showed that H2O2 could promote HSC proliferation. In contrast, IH764-3 at concentrations of 10 mg/L, 20 mg/L, 30 mg/L and 40 mg/L inhibited its proliferation. The inhibition rates were 7.13%, 28.36%, 53.80% and 73.10% (P < 0.01). And the inhibition rates of IH764-3 at concentrations of 30 mg/L at 12 h, 24 h and 48 h were 22.24%, 40.51% and 61.65%. Furthermore, IH764-3 could also induce the HSC apoptosis in dose-dependent an dtime-dependent manners (P < 0.01). In addition, after exposed of HSCs to IH764-3 for 24 h, ERK production decreased and ERK1 mRNA was down-regulated earlier about 2 h after exposure to IH764-3. CONCLUSION: IH764-3 may inhibit the proliferation and induce apoptosis of HSCs in both dose-dependent and time-dependent manners, which may be related to down-regulation of ERK expression. PMID- 22295511 TI - [C6 oral glucose metabolism and differentially expressed genes in livers of 1 type diabetic mice]. PMID- 22295512 TI - [Luteolin reduces cardiac dysfunctions in streptozotocin-induced diabetic rats]. AB - OBJECTIVE: To investigate the effects of luteolin (Chinese Traditional Medicine) on cardiac functions and mitochondrial oxidative stress in streptozotocin (STZ) induced diabetic rats. METHODS: Male SD rats were randomly divided into a normal control group, a luteolin control group, a diabetic group, and diabetic groups orally administered with a low dose (10 mg/(kg x d)) or a high dose of luteolin (100 mg/ (kg x d)) for eight weeks. The body weight, blood glucose, cardiac functions, left ventricular weight, myocardial collagen and reactive oxygen species (ROS) levels were assayed. The cardiac mitochondrial ROS level, superoxide dismutase (SOD) activity and the mitochondrial swelling were measured. RESULTS: Treatment with luteolin had no effect on the blood glucose but reduced the losing of body weight in diabetic rats. High dose of luteolin markedly reduced the ratio of ventricular weight and body weight, increased the left ventricular develop pressure, and decreased the left ventricular end diastolic pressure in diabetic rats. The myocardial levels of ROS and collagen, the cardiac mitochondrial ROS level, and the mitochondrial swelling in diabetic rats were all markedly reduced by high dose of luteolin. Furthermore, high dose of luteolin significantly increased the mitochondrial SOD activity in diabetic rat hearts. CONCLUSION: Treatment with luteolin for 8 weeks markedly improves the cardiac function, which may be related to reducing mitochondrial oxidative stress and mitochondrial swelling in diabetic rats. PMID- 22295513 TI - [The impact study of blood glucose and lipid metabolism on diabetic rats by drinking beer and exercise]. PMID- 22295514 TI - [Effect of Pulsatilla Decoction on the expression of proinflammatory cytokines in inflammatory bowel disease]. AB - OBJECTIVE: To investigate the molecular mechanisms underlying in the treatment of inflammatory bowel disease by Pulsatilla Decoction. METHODS: Forty Wistar male rats were randomly divided into 5 groups( n = 8)control group, model group, model + positive control group (mesalazine), Pulsatilla Decoction treatment group, in addition, the Pulsatilla Decoction treatment group was divided into middle and high dose group. Intragastric administration was used in the positive control group and Pulsatilla Decoction treatment group. The expression of interleukin 1beta (IL-1beta), interleukin-6(IL-6) and tumor necrosis factor-alpha (TNF-alpha) were detected by real time PCR after extraction of RNA from colons. RESULTS: Compared with the model group, positive medicine and Pulsatilla Decoction group, especially high-dose group, could effectively inhibit the expression of IL-1beta, IL-6 and TNF-alpha. CONCLUSION: Pulsatilla Decoction could exert its effect in the treatment of inflammatory bowel disease by inhibiting the expression of proinflammatory cytokines. PMID- 22295515 TI - [Eeffects of Coptis Chinensis on vasoconstrictive activity of isolated thoracic aorta of normoxic and chronic intermittent hypobaric hypoxic rats]. AB - OBJECTIVE: To observe the effects of Coptis Chinensis on vasoconstrictive activity of isolated thoracic aorta rings of normoxic and chronic intermittent hypobaric hypoxic (CIHH) rats, and to investigate the underlying mechanisms. METHODS: Young male Sprague-Dawley rats were randomly divided into normoxic group and CIHH group: the fonnrmer were not given any special treatment; the latter were exposed to hypoxia in a hypobaric chamber simulating 5000 m altitude (PB = 404 mmHg, PO2 = 84 mmHg, 11.1% O2), 6 hours daily for 28 days. The isolated thoracic aorta rings of rats were prepared and perfused in thermostat, and the effects of Coptis on vasoconstrictive activity of aorta rings were recorded, the mechanisms were investigated simultaneouly. RESULTS: Coptis Chinensis significantly decreased NE and KC-induced vasoconstriction of normoxic and CIHH rats' isolated aortic rings, but the inhibitive effects had no obvious discrepancy between the two groups. The contractive amplitude had no marked change after the removal of endothelium. When calculated by Logit Loglinear analysis, IC50 of NE and KCl-induced contractive amplitude in normoxic group were respectively 2.99 g/L and 6.14 g/L, while they were 3.45 g/L and 5.81 g/L in CIHH group. The inhibitive effect of Coptis on vasoconstrictive activity of both groups could be partly decreased by Glibenclamide and nitro-L-arginine methyl ester; Indomethacin suppressed the effect on normoxic group as well. Also Coptis significantly inhibited NE-induced both intracellular and extracellular calciumion-depended vasoconstriction. CONCLUSION: Coptis Chinensis obviously relaxes isolated thoracic aorta rings of normoxic and CIHH rats, but the effects are endothelium-independent and have no marked discrepancy between the two groups. The mechanisms of the effects may be related to the opening of ATP sensitive K+ channel, raise of nitric oxide concentration in both groups, and the increasing of PGI2 in normoxic group. Besides, Coptis may inhibit sarcoplasmic reticulum releasing Ca2+ and decrease the inflow of extracellular Ca2+ via cell membrane. PMID- 22295516 TI - [Prevention of immersed hypothermic dogs with nimodipine]. PMID- 22295517 TI - [Changes of subthalamic nucleus and cortex activity in rat during exhausting exercise]. AB - OBJECTIVE: To observe the modulatory effect of subthalamic nucleus (STN) on activity of motor cortex during exhausting exercise. METHODS: Electrocorticogram (ECoG) and local field potentials (LFPs) recording techniques were applied simultaneously to observe the dynamic changes of oscillations in sensorimotor area and STN of rat during exhausting exercise. RESULTS: Rats ran well initiatively with treadmill at the beginning of the exercise, about 45 min (45 +/ 11.5) later, movement capacity reduced. Corresponding electrical property showed that STN activity increased significantly while activity of cortex decreased significantly. Subsequently rats continued exercise with minor external stimulation utill exhaustion. Activity of ECoG reached the minimum under exhausting stations (P < 0.01), while the activity of LFPs changed insignificantly (P > 0.05). CONCLUSION: During the exhausting exercise, the cortex activity was extensively depressed with the development of fatigue, while the activity of STN increased significantly at the early stage of fatigue, STN took part in the modulation of central fatigue through negative induction. And the increase of STN activity may be one of the key measures accounting for protective inhibition. PMID- 22295518 TI - [Dynamic changes of 5-HT, DA and their metabolin in rat striatum during exhaustive exercise and recovery]. AB - OBJECTIVE: To study the dynamic characteristics of serotonin (5-HT), dopamine (DA) and their metabolin changes in brain during the development of exercise induced central fatigue. METHODS: Coupling of microdialysis and capillary electrophoresis-laser induced fluorescence detection method were used to continuously monitored the changes of DA, tryptophan (Trp), tyrosine (Tyr), 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in striatum extracellular fluid during the exhaustive exercise and recovery time. RESULTS: The concentrations of Trp, 5 HT, 5-HIAA in striatum extracellular fluid had no remarkable changes in the early time of exercise (P < 0.05), while they significantly increased during the later time of exercise and whole recovery time (P < 0.05, P < 0.01). The concentrations of DA and Tyr significantly increased over basal level in the later exercise time, exhaust and recovery time (P < 0.05, P < 0.01). DA/5-HT significantly increased in the initial time of exercise (P < 0.05, P < 0.01), while decreased during the later exercise time, the nadir occurred at 15 minutes before rats exhausted. DA/5-HT slightly recovered back to basal level during the recovery time, and there was no significant difference during later exercise, exhausted and recovery time compared with basal level (P < 0.05). CONCLUSION: The changes of DA and 5-HT in striatum have phase characteristics. Both of them significantly increase during the development of exercise-induced fatigue. However, the 5-HT plays the dominant role in the dynamic changes of them. PMID- 22295519 TI - [Effects of puerarin on blood pressure, blood lipid and renal structure of cold induced hypertensive mice]. PMID- 22295520 TI - [Effects of Chinese herbal compound on monoamine and neuronal amino acids in rat's telencephalon in the course of exhaustion and recovery process]. AB - OBJECTIVE: To observe the effect of Chinese herbal compound on variance of neurotransmitters in rat telencephalon and to further discuss the mechanism underlying Chinese herbal compound in improving exercise capacity and promoting recovery from exercise-induced fatigue. METHODS: 64 rats (8 week old) were randomly divided into medicine group (MG) and control group (CG). Chinese herbal compound was administered to rats of MG for 8 weeks. 8 weeks later, every group was divided into 4 subgroups and all were killed at different time point separately, and then neurotransmitter in rat brain was tested. RESULTS: The exhaustion time of MG was significantly longer than that in CG (P < 0.01). In rest conditions, glutamic acid (GLU) of MG was significantly higher than that in CG (P < 0.01), while, there were no significant differences between MG and CG in other indexes. After fixed quantitative load exercise, the content of 5 hydroxytryptamineZZ(5-HT), 5-hydroindole acetic (5-HIAA), gamma-aminobutyric acid (GABA), Dopamine (DA) and 5-HT/5-HIAA were significantly lower than those in CG, while, GLU, GLU/GABA and DA/5-HT were significantly higher than those in CG. Compared with CG, exhaustion significantly (P < 0.05) decreased 5-HT, GABA and 5 HT/5-HIAA, and significantly (P<0.05) increased GLU, DA/5-HT and GLU/GABA level in MG. 12 h after exhaustion, in contrast to CG, level of 5-HT and 5-HT/5-HIAA in MG were significantly (P < 0.01) lower while GLU, DA, GABA and DA/5-HT were significantly (P < 0.01) higher. CONCLUSION: During exhaustion exercise, Chinese herbal compound demonstrated strong inhibiting effect on synthesis of 5-HT, 5 HIAA, DA, GABA and promoting effect on GLU synthesis, this had been confirmed by the combined effect, including increase of excitatory transmitter and excitability of central nervous system and the prolongation of exhaustion time and promoting recovery from fatigue. PMID- 22295521 TI - [Experimental study of interference of antipyretic-detoxicate TCM in acute myocardial ischemic injury in rats]. PMID- 22295522 TI - [Study on the effect of cardioplegia induced by kalium-verapamil-propranolol in different temperatures on the function of immature rat heart]. AB - OBJECTIVE: To explore the appropriate temperature of the kalium-verapamil propranolol (KVP) cardioplegia by observation of the effect on the function of the immature rat heart. METHODS: Isolated hearts from immature rats were perfused by Langendorff method, and assigned to 1 of the following 5 groups (n = 6-8): control, continuously perfused for 170 min at 36 degrees C, normal temperature, normal perfused for 20 min, changed to perfuse with KVP for 3 min then no perfusion 87 min (ischemia 90 min), followed by 60 min reperfusion. 3 groups of low temperature, perfused for 15 min, cool down to 32 degrees C, 28 degrees C and 24 degrees C especially in 5 min, and at 20th min. heart rate (b/min), tension (g), contraction force (g), peak systolic velocity (dT/dt(max)), peak diastole velocity (dT/dt(max)), coronary flow (Drop/min) were monitored during the whole perfusion. RESULTS: Compared to control group, the heart tension increased after 50 min KVP ischemia. The protection of KVP in normal temperature (36 degrees C) was better than lower temperature (32 degrees C, 28 degrees C, 24 degrees C) such as reducing bad contraction, keeping normal myocardium tension,recovering heart rate, recovering the fuction of contraction force and protecting the coronary flow. CONCLUSION: The KVP cardioplegia in normal temperature has the better effect than that in hypothermia to protect the immature heart. PMID- 22295523 TI - [Effects of electroacupuncture stimulation on the activation of endogenous neural stem cells in stroke rats]. PMID- 22295524 TI - [Experimental study of MMP-2 inhibitor treatment of experimental autoimmune myocarditis in Lewis rats]. AB - OBJECTIVE: To investigate the inhibitor of matrix metalloproteinase-2 (MMP-2) (2R)-2-[5-[4-[ ethyl-methylamino] phenyl [thiophene-2-sulfonylamino]-3 methylbutyric acid (TISAM) therapeutic effect on experimental autoimmune myocarditis (EAM) in Lewis rats. METHODS: Treatment protocol of oral administration of 5 mg/kg TISAM once a day for 14 days was performed on EAM Lewis rats. EAM Lewis rats were divided into 3 groups: treatment in early, middle and later stage respectively (n = 20). After experiment at the designate time point, the rats were euthanatized and hearts were harvested. Cardiac inflammatory score, fibrosis score and content, and infiltration of macrophages and T lyminflammatory score, fibrosis score and content, and infiltration of macrophages and T lymphocytes, message RNA (mRNA) expression of matrix metalloproteinase (MMP)-2 and MMP-9 and protein activity of gelatinase were determined. RESULTS: TISAM treatment in early phase was invalid (treatment started from the creation of the model), treatment in middle and later phase was effective (treatment started from 7 and 14 day after the creation of the model). CONCLUSION: Inhibitor of MMP-2 can block ventricular remodeling in middle stage in EAM Lewis rats. The mechanism maybe alleviate the inflammatory cell cardiac infiltration, decrease the mRNA expression of MMP-2 at transcript level and downregulate gelatinase activity at protein level. PMID- 22295525 TI - [Effect of oxidative stress in development of acute high altitude response during the process of strong physical work at high altitude]. AB - OBJECTIVE: To assess the effect of oxidative stress in development of acute high altitude response (AHAR) during the process of strong physical work at high altitude and its change after return to lower altitude. METHODS: Ninety-six officers and soldiers of rapid entering into high altitude (3 700 m) with strong physical work were analyzed, all subjects were male, aged 18-35 years. According to the symptomatic scores of AHAR were divided into 3 groups: severe AHAR (group A, n = 24), mild AHAR (group B, n = 47) and without AHAR (group C, n = 25). Levels in serum 8-iso prostaglandinF2alpha(8-iso-PGF2alpha), superoxide dismutase (SOD) and malonaldehyde (MDA) were measured at higher altitude stayed 50 d and after return to lower altitude (1 500 m) 12 h and 15 d, and 50 healthy volunteers (group D) at 1 500 m altitude served as controll. RESULTS: Levels of serum 8-iso PGF2alpha and MDA [(9.53 +/- 0.47) microg/L, (8.91 +/- 0.39) micromol/L] were significantly higher in group A than those in group B [(8.34 +/- 0.42) microg/L, (7.31 +/- 0.32) micromol/L] , group C [(7.02 +/- 0.48) microg/L, (6.41 +/- 0.23) micromol/L] and group D [(5.13 +/- 0.56) microg/L, (5.48 +/- 0.33) micromol/L], (all P < 0.01), and serum SOD [(52.08 +/- 3.44) micro/ml] was significantly lower in group A than that in group B [62.27 +/- 2.54) micro/ml], group C [(71.99 +/- 3.35) micro/ml] and group D [(80.78 +/- 3.44) micro/ ml] (all P < 0.01), there were significant differences between group B and C, C and D (all P < 0.01). At altitude 3 700 m 50 d, AHAR scores was positively correlated with serum 8-iso PGF2alpha and MDA (all P < 0.01), negatively correlated with SOD (P < 0.01). Serum 8-iso-PGF2alpha and MDA were negatively correlated with SOD (all P < 0.01). Levels of serum 8-iso-PGF2alpha and MDA were significantly higher at altitude of 3 700 m 50 d than those at altitude of 1 500 m 12 h,15 d in group D (all P < 0.01), and serum SOD was significantly lower than that at 1 500 m 12 h,15 d in group D (all P < 0.01), there were significantly difference between at 1 500 m 12 h and 15 d (all P < 0.01), there were no difference between at 15 d in group D (all P > 0.05). CONCLUSION: The more serious of oxidative stress and oxidative/antioxidative imbalance, the more serious of AHAR, oxidative stress and oxidative/antioxidative imbalance may be involved in the development of AHAR. The changes were obviously improved after return to lower altitude 12 h, and recovered to normal after 15 d. PMID- 22295526 TI - [Lipid peroxidation and biomechanical properties of artery in hyperlipemia rats after treating with tetrahydrobiopterin]. AB - OBJECTIVE: To explore the effect of the level of lipid peroxidation and biomechanical properties after chronic treating with tetrahydrobiopterin (BH4) in thoracic aorta of hyperlipemia (HL) rats. METHODS: HL rats were given BH4 chronically. The opening angle in the zero-stress state and the relationship between pressure and diameter (P-D) of mesenteric artery were measured by computer image 8, 16, and 24 week-old respectively. RESULTS: Treating with BH4 chronically from 8 week-old in HL rats, there was a significant increase in the zero-stress state of opening angle of thoracic aorta. The P-D curve of mesenteric artery moved upward. CONCLUSION: Treating with BH4 prevented the structure and function of artery from abnormal changing, and attenuated lipid peroxidation in HL rats. PMID- 22295527 TI - [Identification of differentially expressed genes in rats and preliminary analysis in regression of vascular calcification]. AB - OBJECTIVE: To investigate the differentially expressed genes in rat in the process of regression of vascular calcification by using the suppression subtractive hybridization (SSH). METHODS: 24 SD male rats which aged 6 weeks and specific pathogen free grade were selected and randomly divided into 3 groups (n = 8): control group, calcification group and regression group respectively. Vascular calcification model (vitamin D3 plus nicotine, VDN) were made from rats in calcification group and regression group, and rats in control group were intragastric administered with normal saline and lavaged with peanut oil. Rats were bred for 8 weeks in calcification group and control group, while rats in regression group were fed for 16 weeks. All rats were killed to measure concentration of calcium in the arterial tissue and examine the pathological lesion changes. Subtractive hybridization among vascular cDNA sequences from calcification group and regression group were established. The cDNA fragments which expressed higher or lower in regression group than those in calcification group were isolated. Differentially expressed genes with cDNA fragment were inserted into PMD18-T plasmid vector and transformed competent DH-5alpha, cDNA libraries of differentially expressed gene between calcification group and regression group were then constructed. Recombinant vectors were analyzed by colony PCR, positive genes were randomly selected for sequencing and analyzed by BLAST. 4 genes were randomly selected for RT-PCR certification combined with semi quantitative analysis of DNA bands. RESULTS: VDN model of rats were successfully constructed. Concentration of tissue calcium in calcification group (15.34 mg/g +/- 2.51 mg/g) was significantly increased compared to that in control group (5.20 mg/g +/- 0.75 mg/g, P < 0.001), while in comparison with calcification group (15.34 mg/g +/- 2.51 mg/g), calcium in regression group was relatively lower (12.73 mg/g +/- 1.89 mg/g, P < 0.05). 28 up-regulated genes and 22 down regulated genes were gained through sequencing and BLAST analysis among positive clones. RT-PCR validation indicated that 4 genes such as prdx3 and Ank2 had increasedly expressed in regression group than those in calcification group, the average fold change was 1.7. CONCLUSION: Rat vascular calcification tissue had characteristic of active regression. Genes in relation to pyrophosphoric acid synthesis, glutamate signal peptides, anti-oxidant and ant-apoptosis were up regulated, at the same time many genes related to ossification and oxidation activity were down-regulated in the process of calcification regression. Increased expression of calcification suppressor genes accompanying decreased expression of calcification promoting genes might be the intrinsic mechanisms which initiated the active regression of calcified tissues. PMID- 22295528 TI - [The time order of autophagy and apoptosis process in the oxidative injury in glioma U251 cells]. AB - OBJECTIVE: To investigate the time order of autophagy and apoptosis in human U251 cells injury after H2O2 treatment. METHODS: 4 groups in this study were set up, normal control group, 1 mmol/L H2O2 (6 h,12 h, 24 h) group. The viability of U251 cells treated with H2O2 was measured by MTT assay. Cell apoptotic ratio was determined by flow cytometry analysis. Autophagic vacuoles were stained with monodansylcadaverine. The protein level of Beclin 1 and cytosolic cyt c were assayed by using Western blot. RESULTS: Compared with the control group, cell viability decreased significantly under 1 mmol/L H2O2 treatment in time-dependent way. Autophagic vacuoles and the expression of autophagic protein Beclin 1 increased at 6 h, but cell apoptotic ratio and cytosolic cyt c protein did not change obviously, cell apoptotic ratio and cytosolic cyt c protein level increased at 12 h and 24 h (P < 0.05). CONCLUSION: Oxidative stress induced autophagy and apoptosis in U251 glioma cells, and autophagy eventuated ahead of apoptosis. PMID- 22295529 TI - [Orbitofrontal cortex action of 5-hydroxytryptamine, glutamate and nitric oxide in an acute forced swimming stress-induced depression model]. PMID- 22295530 TI - [The correlation analysis of carotid stenosis and pulse pressure in the elderly men with essential hypertension]. AB - OBJECTIVE: To investigate the relationship between the carotid stenosis (CS) and the pulse pressure (PP) in elderly men with essential hypertension. METHODS: According to the Color Doppler Flow Imaging (CDFI), 157 elderly men with essential hypertension and carotid atherosclerosis were divided into five classifications and two groups: CS < 50% group (n = 66) and CS > or = 50% group (n = 91). The blood pressures were measured within one year before the CDFI was taken and clinical data were recorded. RESULTS: (1) The systolic blood pressure (SBP) and the PP in CS > or = 50% group were significantly increased than those in CS < 50% group, while the diastolic blood pressure (DBP) was converse. The independent risk factors of CS > or = 50% were peripheral arterial disease (OR: 4.543, 95%CI: 1.415-14.590) and PP (OR: 1.096, 95% CI: 1.038-1.157). (2) CS classifications positively correlated with PP (r = 0.402, P < 0.01) and fibrinogen (FIB) (r = 0.200, P < 0.05). After adjusting for age, body mass index (BMI), SBP, DBP, total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), fasting serum glucose (FBG), blood uric acid (UA), D-dimer, amino-terminal pro brain natriuretic peptide (NT-proBNP), total bilirubin (TBIL) and direct bilirubin (DBIL), multiple regression analysis showed that PP and FIB remained as predisposing risk factors for CS classifications. CONCLUSION: The pulse pressure was correlated with carotid stenosis in elderly men with essential hypertension and it was justified for concurrent inhibition of PP in the treatment of high blood pressure. PMID- 22295531 TI - [Protective function of melatonin to acute lung injury and its mechanisms in rats caused by oleic acid]. AB - OBJECTIVE: To observe the expression of P-selectin (Ps), intercellular adhesion molecule-1 (ICAM-1) and nuclear factor-kappa B (NF-kappaB) in lung tissues of acute lung injury (ALI) rat model induced by oleic acid (OA) and to explore the protective effects of melatonin (MT) in lung tissues in rats. METHODS: All rats were randomly divided into four groups: control group, OA group, MT + OA group and SB203580 + OA group. Rat model of ALI was established by intravenous injection of oleic acid (OA). Lung coefficient was measured, lung tissues were imbedded by paraffin to observe morphological changes and the expression of Ps, ICAM-1 and NF-kappaB in lung tissues by means of immunohistochemistry staining. RESULTS: Compared with control group, the lung coefficient increased significantly in OA group (P < 0.05). Alveolar septum thickened significantly in OA group, there had many infiltrated inflammatory cells and collapsed alveoli of lung; positive expression of Ps, ICAM-1 and NF-kappaB were very obvious (P < 0.05); the administration of MT and SB203580 mitigated above changes significantly (P < 0.05). CONCLUSION: MT possesses obviously protective effect on lung tissues during ALI, its protective mechanism might be related to the inhibition of the expression of Ps, ICAM-1 and NF-kappaB. PMID- 22295532 TI - [Effects of Trillim tschonskii maxim on microvessels response and anti-oxidation enzyme in burned rats]. PMID- 22295533 TI - [Effects of hydrogen sulfide on pulmonary surfactant in rats with acute lung injury induced by lipopolysccharide]. AB - OBJECTIVE: To observe the changes of pulmonary surfactant (PS) in rats with acute lung injury(ALI) induced by lipopolysaccharide (LPS) and to explore the effects of hydrogen sulfide (H2S) on PS. METHODS: Fourty- eight male rats were randomly divided into six groups (n = 8). They were control group, LPS group, LPS+ NaHS low, middle, high dose groups and LPS+ PPG group. Saline was administrated in Control group. LPS was administrated in LPS group. In LPS + NaHS low, middle, high dose groups or LPS + PPG group, sodium hydrosulfide (NaHS) of different doses or DL-propargylglycine (PPG) were respectively administrated when the rats were administrated of LPS after 3 hours. All the rats were killed at 6 hours after administration of Saline or LPS. The morphological changes of alveolar epithelial type II cells (AEC-II) were respectively observed by transmission electron microscopes. The content of H2S in plasma and activity of cystathionine gamma-lyase (CSE) in lung tissues were respectively detected. The contents of total protein (TP) and total phospholipids (TPL) in bronchoalveolar lavage fluid (BLAF) were respectively measured. The pulmonary surfactant protein A (SP-A), surfactant protein B (SP-B) and surfactant protein-C (SP-C) mRNA expressions in lung tissues were analysed. RESULTS: (1) Compared with control group, the content of H2S in plasma, activity of CSE, content of TPL, and SP-A, SP-B and SP-C mRNA expressions were respectively decreased in LPS group (P < 0.05 or P < 0.01). But the content of TP was increased in LPS group (P < 0.01); (2) Compared with LPS group, the content of H2S, activity of CSE and SP-A mRNA expression were significantly increased in LPS + NaHS low, middle and high dose groups (P < 0.05). The SP-B mRNA expression and content of TPL were significantly increased in LPS + NaHS Middle and High dose groups (P < 0.05). The content of TP was decreased in LPS + NaHS High dose group (P < 0.05). The SP-C mRNA expression was not altered in LPS+ NaHS low, middle and high dose groups (P > 0.05); (3) Compared with LPS group, the content of H2S, activity of CSE, content of TPL, and SP-A, SP-B and SP-C mRNA expressions were respectively decreased, but content of TP was increased in LPS + PPG group (P < 0.05). CONCUSION: The decrease of PS is the important physiopathologic process of ALI induced by LPS. Exogenously applied H2S could attenuate the process of ALI that possibly because H2S could adjust the compose and secretion of PS. PMID- 22295534 TI - [Preliminary study about the role of c-src in the initiation of primordial follicle in rat ovary]. AB - OBJECTIVE: To explore the role of c-src on the initiation of primordial follicles. METHODS: 2-days-old female SD rats' ovaries were cultured in Waymouth culture system and were used HE staining and immunohistochemy to observe the number of follicles after 0, 4, 8 days cultured. Use chemically synthesized small interference RNA (siRNA) transfected into ovarian tissue in cultured for RNA interference, and use HE staining and RT-PCR to detect the best siRNA and packaging it by lentiviruses to test the interference effect. RESULTS: With the increase of culturing days, the nummber of the primordial follicles in ovarian gradually reduced. We packed the best siRNA by lentiviruses to doing RNA interference and found comparing with the blank control group and blank vector group, c-src mRNA of the best interference group were significantly decreased. The total number of primordial follicles was relatively greater and the development of primordial folliculars was inhibited. CONCLUSION: c-src plays an important role in primordial follicle development and folliculogenesis initiation. PMID- 22295535 TI - [Clinical observation of injection of dexmedetomidine in anaesthesia for esophageal cancer operation]. AB - OBJECTIVE: To investigate the effects of administration of dexmedetomidine in anaesthesia for esophageal cancer operation. METHODS: 100 patients (ASAI-II) who were undergoing to esophageal cancer operation were randomly divided into control group (group A) and dexmedetomidine group (group B) (n = 50). The scheme of induction and maintenance of aesthesia of the two groups were identical. Patients in group B administered dexmedetomidine at a dose of 1 microg/kg over 10 min and patients in group A were given a placebo infusion of normal saline. Patients in group B administered dexmedetomidine at a dose of 0.4 microg/(kg x h) was injected and stoped at 30 min by the end of operation. Mean artery pressure (MAP) and heart rate (HR) were detected before induction (T0), induction (T1), 1 min after extubation (T2), 5 min after extubation (T3) and 10 min after extubation (T4) Propofol comsumption, fentanlyl comsumption, and side effects were recorded as well. RESULTS: The results showed that MAP and HR (T0, T1, T2, T3, T4) in group B were significantly different from those in group A which fluctuated more markedly (P < 0.05). Propofol comsumption in group A was much more than that in group B (P < 0.05). Incidence of pharynx and larynx ache and restlessness were higher in group A than those in group B (P < 0.05). CONCLUSION: Dexmedetomidine could effectively reduce the cardiovascular response to incubation and extubation in esophageal cancer operation patients. Propofol comsumption, fentanlyl comsumption and side effects were reduceed as well. PMID- 22295536 TI - [Optimization of electroporation parameters in HL-60 cells for STIM1 siRNA interference during its differentiation]. PMID- 22295537 TI - [The influence of contraction modes on the phosphorylation of p38/Akt]. AB - OBJECTIVE: Muscle contraction may prompt glucose uptake through non-insulin dependent ways, and it may be due to the enhanced activation of key proteins known to regulate glucose metabolism, like p38 and Akt. Our experiment focused on the impact of different contraction modes on the phosphorylation of the molecules, thus to explore effective ways to lower blood glucose. METHODS: Isolated muscle strips perfusion technique and Western blot analysis were employed to investigate the influence of different modes of contraction on the activation of the molecules. RESULTS: Muscle contraction led to an increase in p38 phosphorylation, with the greatest effect observed after 5 minutes of 10% DC (duty cycle) contraction and 5 minutes of 1% DC contraction. However, phosphorylation of Akt were not altered by the two contraction modes. CONCLUSION: The level of phosphorylation of p38 was higher at the optimal contraction modes, but these modes could not increase the level of phosphorlation of Akt. PMID- 22295538 TI - [Heart-rate threshold study on fitness and bodybuilding load training]. PMID- 22295539 TI - [Apparatus for the measurement of the oxygen uptake of rats subjected to hypobaric hypoxia]. AB - OBJECTIVE: To construct an apparatus for the oxygen uptake measurement of rats exposed to hypobaric hypoxia at different simulated altitude. METHODS: The capacity of this apparatus was about 0.01 m3. It included animal experimental cabin, reference cabin, altimeter, altitude vertical velocity indicator, pressure difference inductor and oxygen compensator, low scale manometer, soda lime and calcium chloride, small fan, thermometer, circulating water system and vacuum pump. The oxygen uptake of the rats at 6 000 m, 4 000 m and 1 000 m simulated altitude was measured using this apparatus. RESULTS: The oxygen uptake of the rats at 50 m, 4 000 m and 6 000 m simulated altitude was (24.4 +/- 2.1), (10.8 +/ 2.0) and (8.8 +/- 1.6) ml O2/(kg x min) respectively (average +/- s, n = 10). The oxygen uptake decreased as altitude increased. CONCLUSION: This apparatus can be used to measure the oxygen uptake of the rats at different simulated altitude. PMID- 22295540 TI - [A method of acutely isolating rat dorsal root ganglion neurons for patch-clamp study of single-channel]. AB - OBJECTIVE: To establish a method of acutely isolating dorsal root ganglion (DRG) neurons for patch clamp study of single-channel. METHODS: DRG neurons of rats were acutely isolated by enzymatic digestion and mechanical blowing. RESULTS: The acutely isolated DRG cells were easy to form the higher sealing resistance (> 5G Omega), which lowered noise level, so that pA-level single channel currents could be recorded. CONCLUSION: The acutely isolated DRG neurons in this study are an ideal for patch-clamp study of single-channel. PMID- 22295541 TI - [A portal vein branch embolization as a method of preparation for liver resection]. AB - The results of preoperative transcutaneous transhepatic embolization of portal vein (PTTEPV) were analyzed in 86 patients, suffering malignant hepatic tumors. Depending on a planned hepatic resection (HR) volume there was conducted embolization of a right lobar portal vein (in 45 patients), right vein with a vein of C(IV) segment (in 32), lobar portal vein with anterior right vein (in 9). In 3-4 weeks after PTTEPV there was noted the enhancement of ratio of a planned residual hepatic volume/total hepatic volume from 16.3 to 27.5%, permitting to perform HR successfully in these patients. In 4 (4.7%) patients HR was not performed because of progressing of the tumor development or a total thrombosis of portal vein. The data obtained witness, that PTTEPV constitute an effective method of the patients preparation for HR while presence of a planned small residual hepatic volume. PMID- 22295542 TI - [Methabolism of connective tissue in patients with complicated chronic pancreatitis]. AB - A content in the blood serum of a free and connected oxyproline, collagenolytic activity of the blood, the level of glycosaminoglycans and elastase activity was detected in chronic pancreatitis (CHP). There were examined 73 patients (64 men and 9 women). CHP in a stage B (according to M. Buchler et al., 2009) was established in 26 (35.6%) patients, C1 - in 18 (24.6%), C2 - in 17 (23.4%), C3 - in 12 (16.4%). A progress of pancreatic fibrosis in CHP have occurred on a background of a high activity of elastase in neutrophils, a glycosaminoglycans level raising, as well as a free and connected oxyproline. A detection of a neutrophils elastase activity and oxyproline content in the blood serum may be used in a clinical practice as additional diagnostic criteria of estimation of the pancreatic pathology severity. The changes revealed were the same as in CHP of alcoholic and of the other nature. PMID- 22295543 TI - [Tactics of preoperative infusion therapy in obturation jaundice]. AB - The influence of the infusion therapy content on a hepatic function of bile outflow (HFBO), a bilirubin content and the enzymes activity in obturation jaundice in 139 patients was studied up. In 54 patients (the first group) a Ringer solution and 10% solution of glucose in 1:1 ratio were applied; in 37 patients (the second group) - a sterofundin-G-5 solution; in 48 patients (the third group) - remaxol in a dose of 800 ml/day. Application of sterofundin-G-5 and remaxol as a component of infusion therapy have promoted a bile outflow intensity enhancement in early postoperative period in comparison with such while Ringer solution and 10% solution of glucose application. Remaxol more effectively have eliminated a hyperbilirubinemia, enzymemia and a HFBO disorder, than sterofundin-G-5. PMID- 22295544 TI - [Renal arteries stenting using distal antiembolic devices]. AB - Endovascular treatment of vasorenal hypertension (VRH) constitutes the operation of choice in selected groups of patients. In the Centre there was conducted a renal arteries (RA) stenting, using antiembolic devices in 6 patients (4 men and 2 women). There were applied distal filters Accunet (Abbot Vascular, USA) 12 mm in length with diameter of a cell 150 mcm. The devices application, having a net structure, is possible in optimal anatomy of artery (rectangular branching), significant stenosis of RA, primarily bad renal function, a presence of anatomically loose plaque in RA, atherosclerotic ulceration of the abdominal aorta wall. There are limitations of their application: an ischemia while performing of the procedure, complexity of the stenotic region visualization, as well as a control of a precise delivering and implantation of a stent-system and a possibility of the embolism occurrence after extraction of occluding balloon. PMID- 22295545 TI - [Gastric secretory function in patients with chronic renal insufficiency and gastroduodenal hemorrhage]. AB - Gastric hypersecretion occurrence in patients, suffering chronic renal insufficiency (CHRI), creates conditions for acido-peptic gastroduodenal zone affection with possible formation of erosive-ulcerative defects, complicated by hemorrhage. In 116 patients, suffering CHRI, the state of gastric mucosa secretory function was studied up. In patients with an acute gastrointestinal hemorrhage and CHRI in conservative and terminal stages the analysis of acidity was conducted. PMID- 22295546 TI - [Dynamics of content of inflammatory acute phase proteins in extended peritonitis]. AB - There were analyzed the results of surgical treatment of 60 patients, suffering extended peritonitis (EP), in whom the content changes in the blood serum, concerning the acute phase of inflammation proteins (C-reactive protein, lactoferrin and ferritin) were studied. To all the patients a conventional basic intensi therapy was conducted postoperatively. The EP course severity was estimated using Manheim's peritoneal index (MPI): in 17 patients a I degree MPI was established, in 23 - MPI of II degree, in 20 - MPI of III degree. According to the investigation results obtained, there was established, that severity of changes of the studied indices depends on the disease course severity. The adduced indices detection makes it possible to estimate a severity of inflammatory process and efficacy of treatment conducted. PMID- 22295547 TI - [Antiatherogenic effect of abdominoplasty in patients with anterior abdominal wall deformity and obesity]. AB - The impact on a lipids metabolism of a certain volume of fat tissue extraction from organism was investigated. With that objective there was determined the lipids content in a blood serum before and on a 14th day after abdominoplasty. In 73 patients (the main group) surgical interventions were performed on the organs of abdominal cavity, small pelvis and anterior abdominal wall with a simultant abdominoplasty, in 59 patients (a comparison group) abdominoplasty was not performed. The lipids metabolism desorders was observed in both groups of patients. The results of operations, conducted with a simultant extraction of a fat tissue were characteristic for positive dynamics of the lipids spectre in the blood. A normalizing impact on the blood serum lipids was caused by a triglyceride depot volume reduction, which promotes a catabolism processes strengthening in atherogenic lipoproteins and stabilizes a nonesterified fat acids concentration on optimal level. The data obtained witness, that abdominoplasty conduction secures antiatherogenic affect in patients, suffering obesity. PMID- 22295548 TI - [Crossectomy conduction under local anesthesia in conjunction with mini-invasive methods of a varicose disease treatment]. AB - Experience of treatment of 135 patients for varicose disease (VD) of lower extremities (VLE) was analyzed. The investigation objective was the elimination of adverse reactions of general anesthesia and minimization of surgical trauma without loss of the operation radicalism. In 112 (83%) patients a crossectomy (upper and/or lower) was conducted under local infiltrating anesthesia. The criterion for the patients choice for the operation in conditions of local anesthesia was the presence of a VD, independent of its stage. In the investigation were not included the patients, suffering a VD recurrence and its decompensated forms. Our experience witness, that in a certain level of a surgeon qualification present, in a majority of patients, suffering VDLE, including its complicated forms, crossectomy may be performed in conditions of a local anesthesia. PMID- 22295549 TI - [Peculiarities of course of an acute varicose thrombophlebitis in elderly and senile patients and effect of age on tactics of surgical treatment and operative treatment volume]. AB - Examination was conducted in 244 elderly and senile patients (60-89 yrs old), suffering an acute varicosothrombophlebitis (AVTH), of them 240 were operated on. The AVTH course peculiarities were studied up, which influenced the tactics choice and have had determined the indications for surgical intervention performance. PMID- 22295550 TI - [Video-assisted thoracoscopic surgeries for thoracic diseases and trauma]. AB - The experience of videothoracoscopic operations, performed for various diseases of the thoracic organs, was summarized. The reduction of the operation traumaticity, the complications rate, lethality, the patients rehabilitation duration permits to consider videothoracoscopic operations as the method of choice in many thoracic diseases and trauma. PMID- 22295551 TI - [Ligation of the retrobulbar vascular-nervous bunch during performance of evisceration and enucleation using titanic clips in ophthalmic surgery]. AB - The efficacy of hemostasis achievement during conduction of a retrobulbar vascular-nervous bunch ligation (RVNBL), using titanic clips while evisceroenucleation performance, was studied up. A comparative analysis of clinical and functional results of surgical treatment of 36 patients, suffering terminal dolorous glaucoma and disaster of a sympathetic ophthalmia complication after an eye penetrating wounding occurrence. In 16 patients (the first group) a standard method of a hemostasis achievement was used while doing evisceroenucleation - a deep orbital tamponade for 5 minutes. In 20 patients (the second group) a procedure of RVNBL was conducted, using titanic clips before the bunch transsection doing. There was established, that while doing a RVNPL using titanic clips, a hemorrhage never occurs, a retrobulbar hematoma do not formated, the soft tissues reaction in the early postoperative period is less pronounced, and the patients postoperative rehabilitation period shortens. PMID- 22295552 TI - [Estimation of postoperative morphological changes in the area of a potential formation of colorectal anastomosis in experiment]. AB - In experiment on 50 white mongrel male rats there were investigated postoperative morphological changes in the area of a potential formation of colorectal anastomosis, occurring after total rectal mobilization performance. There was established, that rectal mobilization, even while securing a blood flow along the main vessels, causes nonreversible ischemic disorders in its wall. The investigation results witness the enhanced risk of the sutures insufficiency occurrence in low colorectal anastomoses and substantiate the expediency of application of prophylactic methods for this complication in a clinical practice. PMID- 22295553 TI - [Investigation of anti-inflammatory action of electromagnetic irradiation of extremely high frequencies in experiment]. AB - There were studied some mechanisms of the effect realization of the extremely high frequency electromagnet irradiation, including modification of the organism immune status as an answer on the irradiation action, manifested by mobilization of ripe CD4+ and CD8+ T-lymphocytes, the interleukins (IL) concentration enhancement, including, IL-1, IL-10, as well as the levels lowering of IL-6 and C reactive protein in the blood serum. There was established, that using a switching on the intermediate signal systems it is possible to induce the directed (antiinflammatory) answer of organism towards the effective parameters of electromagnet irradiation. PMID- 22295554 TI - [Dupuytren's contracture as a separate clinico-nosologic entity and a component of a systemic pathology]. PMID- 22295555 TI - [Cytokines as biomarkers of trauma severity in patients with burns and prognosis of their course severity: new therapeutic possibilities and rethinking of conventional treatment approaches. Part I]. PMID- 22295556 TI - [Restoration of the large bowel continuity leaving the "short" stump]. PMID- 22295557 TI - [Observation of the appendiceal neoplasm and acute cholecystitis]. PMID- 22295558 TI - [Pancreatic head cyst complicated by aortic pseudoaneurism]. PMID- 22295559 TI - [Observation of a foreign body in the appendix]. PMID- 22295560 TI - [The adrenal function insufficiency in combined closed abdominal trauma]. PMID- 22295561 TI - [The method of intestinal diameter adaptation in restoration of its continuity during resection for acute intestinal obstruction]. PMID- 22295562 TI - [Abstracts of the XI Annual Scientific and Practical Conference with International Participation "Wounds, Wound Infections, Plastic Surgeries and Electric Welding of Living Tissues." December 1-2, 2011, Kiev, Ukraine]. PMID- 22295563 TI - [Approaches towards directed DNA integration by the use of retroviral integrases and transposases]. AB - The ability of retroviruses and transposases to insert own genome into a host cell allow us to consider them as a preferable object for constructing gene therapy vectors. However, enzymes that perform the insertion of the genetic material do not display a selectivity towards target nucleotide sequences that results in an almost random DNA introduction into the recipient cell genome. Random insertion leads to mutations which might cause a number of undesirable consequences including neoplastic transformation in the cell. Thereby, in order to achieve a successful functioning of retroviral and trasposonal genetic therapy systems, it is essential to modify them in such a way that directed integration of the vector in a target sequence in the human genome could be achieved. In the review approaches that have been developed for a high specific modification of genome, including the construction of hybrid proteins on the basis of retroviral integrases, transposases, as well as cellular factors interacting with these enzymes, are presented. PMID- 22295564 TI - Expression of anti-neuroexcitation peptide III of scorpion Buthus martensii Karsch BmK ANEP III in plants. AB - Anti-neuroexcitation peptide III of Buthus martensii Karsch (BmK ANEP III) has better anti-epileptic and anticonvulsive effects in the test animal models. The present study is aimed at developing transgenic tomato and tobacco lines overproducing the ANEP III protein. Using the molecular cloning technique, the plant expression vector pBI-ANEP III was constructed successfully. The ANEP III expression cassette included a double CaMV 35S promoter with omega enhancers, the ANEP III gene with the Kozak sequence, the ER retention signal and the NOS terminator. Recombinant plasmids were transferred into Agrobacterium tumefaciens EHA105 by freeze-thaw transformation methods. By the Agrobacterium-mediated leaf disc transformation method, tobacco (Nicotiana tabacum) and tomato (Lycopersicum esculentum) lines were transformed. Transformants were screened and confirmed by PCR, RT-PCR and western blotting analysis. It was demonstrated that the ANEP III gene was successfully expressed in the genomic DNA of transgenic plants. The ANEP III protein was detected by immunofluorescence analysis, and the results confirmed the high amount of ANEP III protein, being 0.81 and 1.08% of total soluble proteins in transgenic tobacco and tomato. The study of plants with high expression levels of ANEP III has an important theoretical and practical significance and provides valuable information for establishing a new, economical and effective system for industrial protein production. PMID- 22295565 TI - Purification, characterization and cDNA cloning of an analgesic peptide from the Chinese scorpion Buthus martensii Karsch (BmK AGP-SYPU2). AB - In this study an analgesic peptide was purified through five continuous chromatographic steps. The mouse twisting model test was used to identify the target peptides in every separation step. The purified BmK AGP-SYPU2 was further qualified by Reverse Phase-High Performance Liquid Chromatography and High Performance Capillary Electrophoresis. The molecular weight, isoelectric point, and N-terminal sequence of the purified peptide were determined. Based on the N terminal sequence, the cDNA was cloned by rapid amplification of the cDNA ends from the cDNA pool of scorpion glands. Sequence determination showed that the mature BmK AGP-SYPU2 peptide is composed of 66 amino acid residues, and BmK AGP SYPU2 is identical to BmK alpha2 (GenBank Acc. No. AF288608) and BmK alphaTX11 (GenBank Acc. No. AF155364). We report herein a purification procedure that yields substantial amounts of natural BmK AGP-SYPU2 with high analgesic activity. PMID- 22295566 TI - [Pharmacogenomics of multiple sclerosis: association of immune response genes polymorphism with copaxone treatment efficacy]. AB - Complex association analysis of copaxone (glatiramer acetate) immunotherapy efficacy with allelic polymorphism in the number of immune response genes, which encode interferone beta (IFNB1), transforming growth factor beta1 (TGFB1), interferone gamma (IFNG), tumor necrosis factor (TNF), interferon alpha/beta receptor 1 (IFNAR1), CC chemokine receptor 5 (CCR5), interleukin 7 receptor alpha subunit (IL7RA), cytotoxic T-lymphocyte antigen 4 (CTLA4) and HLA class II histocompatibility antigen beta chain (DRB1) was performed with APSampler algorithm for 285 multiple sclerosis patients of Russian ethnicity. The results show evidence for the contribution of polymorphic variants in CCRS, DRB1, IFNG, TGFB1, IFNAR1, IL7RA and, probably, TNF and CTLA4 genes to copaxone treatment response. Single alleles of CCR5 and DRB1 genes are reliably associated with treatment efficacy. Carriage of allelic variants of other above mentioned genes contribute with reliable effect to copaxone treatment response as part of bi- and three-allelic combinations only. Present investigation may support basis toward the future possibility of prognostic test realization, which can provide a personal choice of immunomodulatory treatment for a patient with multiple sclerosis. PMID- 22295567 TI - [Identification of genetically modified vegetable sources in food and feed using hydrogel oligonucleotide microchip]. AB - A method of multiplex polymerase chain reaction (PCR) followed by the hybridization on a hydrogel oligonucleotide biochip was developed for simultaneous identification of ten different transgenic elements of plant DNA in feed and food products. The biochip contained 22 immobilized probes intended for (i) detection of plant DNA; (ii) plant species determination (soybean, maize, potato, rice); (iii) identification of transgenic elements, including 35S CaMV, 35S FMV, rice actine gene promoters, nos, 35S CaMV, ocs, pea rbcS1 gene terminators, and bar, gus, nptII marker genes. The limit of detection was 0.5% of genetically modified (GM) soybean and maize in analyzed samples. Identification of transgenic DNA in food and feed products using either the developed approach or real-time PCR led to virtually identical results. The assay can be used for selection of GM samples by screening food and feed products for subsequent quantitative determination of the GM component based on the identified transgene. PMID- 22295568 TI - [Obtaining of fluorescent-labeled nodule bacteria strains of wild legumes for their detection in vive and in vitro]. AB - A series of expression vectors containing genes of fluorescent proteins TurboGFP and TurboRFP under the phage T5 constitutive promoter regulation, intended for lifetime marking of nodule bacteria is created: a series of vectors based on a broad-host-range replicon BBRI, for marking strains with an expression of reporter gene from a transformed plasmid and a series of vectors based on a plasmid pRL765gfp for marking strains by introduction genes of fluorescent proteins in a bacterial chromosome. It was shown that transformation is the most preferable method of constructions transfer in nodule bacteria cells, as in the presence of mob locus in the vectors necessary for conjugation, exists the possibility of occasional plasmid mobilization and its transition from marked strain cells in other soil bacteria. With application of the created vector constructions we obtained fluorescent tagged strains of Rhizobium sp., Mesorhizobium sp., Ensifer (Sinorhizobium) sp., Bradyrhizobium sp., Phyllobacterium sp., Agrobacterium sp. Also their suitability for experiments in vivo and in vitro is shown. PMID- 22295569 TI - [Genome-wide association study of bronchial asthma in the Volga-Ural region of Russia]. AB - Bronchial asthma is a chronic inflammatory respiratory disease that is caused by the complex interaction of environmental influences and genetic susceptibility. The first genome-wide association study of bronchial asthma discovered a significant association between SNPs within 17q12-21 genomic region and childhood bronchial asthma in individuals of European descent. Association with this genomic region was then replicated in a number of independent samples of European and Asian descent. Here we report results of the first genome-wide association study of bronchial asthma in the Volga-Ural region of Russia. The present study includes 358 unrelated patients with physician-diagnosed bronchial asthma and 369 disease-free control subjects of different ethnic origin (Russians, Tatars and Bashkirs). Genotyping of DNA samples was carried out using the Illumina Human610 quad array as a part of GABRIEL project (contract from the EC No LSHB-CT-2006 018996). After QC filtering procedures, a final set of 550915 SNPs genotyped in 330 cases and 348 controls was tested for association with bronchial asthma. Five markers on chromosome 17q12-21 showed statistically significant association with bronchial asthma (p < or = 4.79 x 10(-7)). SNP rs7216389 with the strongest evidence for association (p = 1.01 x 10(-7)) is located within the first intron of the GSDMB gene. Evidence for association was stronger with childhood-onset asthma (p = 1.97 x 10(-6) for SNP rs7216389) compared to late-onset asthma (p = 1.8 x 10(-4) for SNP rs7216389). Our replication study using three SNPs within GSDMB gene confirmed association with only childhood-onset asthma. In summary, these results suggest an important role for genetic variants within 17q12-q21 region in the development of bronchial asthma in the Volga-Ural region of Russia. PMID- 22295570 TI - RKIp inhibits the migration and invasion of human prostate cancer PC-3M cells through regulation of extracellular matrix. AB - Raf kinase inhibitor protein (RKIP) plays a pivotal role in several intracellular signaling cascades and has been implicated as a metastasis suppressor in multiple cancer cells including prostate cancer cells, but the mechanism is not very clear. In this study, we investigated the effect of RKIP on cell proliferation, migration and invasion using human prostate cancer PC-3M cells as a model system. Our results indicate that RKIP does not effect cell proliferation in PC-3M cells, but inhibits both cell migration and cell invasion. In association with this inhibitory effect, RKIP down-regulates matrix metalloproteinases (MMP-2 and MMP 9), cathepsin B and urinary plasminogen activator (uPA). Also RKIP has the ability to regulate the expression of E-cadherin. But ectopic expression of RKIP does not affect the level of the Snail protein. As it has been indicated here, RKIP inhibits the migration and invasion ability of human prostate cancer cells through regulation of the extracellular matrix. These findings provide new mechanistic insight how RKIP suppresses metastasis in vitro. PMID- 22295571 TI - [Some molecular-genetic markers, defining the pathogenesis of superficial and invasive bladder cancer]. AB - We have investigated deletions of 3p14, 9p21, 9q34, 17p13 (TP53) loci, activating FGFR3 mutations in exon 9 and aberrant methylation of RASSF1, RARbeta, P16, P14, CDH1 genes with the aim of the molecular pathogenesis pathways analysis of bladder cancer. FGFR3 activating mutations and 9p21 deletions were observed significantly more frequent in the group of non-invasive bladder cancer pTa than in minimally-invasive cancers pT1 (p = 0.004 and 0.006 respectively). It was shown that groups of superficial and invasive bladder cancer are significantly differing in the frequency of 17p13 (p = 0.006) and 9q34 (p = 0.04) deletions and in aberrant methylation of the gene P16 (p = 0.02). We have revealed some differing molecular-genetic alterations in groups of superficial and invasive bladder cancers. Therefore we suppose that these two types of bladder cancer might have different pathways of development. PMID- 22295572 TI - [Two peroxiredoxins 6 of Xenopus laevis]. AB - Two different genes of peroxiredoxin 6 are encoded in the genome of Xenopus laevis: xen1 (Acc.no. EMBL Data Bank - BCO54278) and xen2 (Acc.no. EMBL Data Bank - BC540309). Both genes were cloned and expressed in Escherichi coil. Proteins were purified and analyzed. The amino acid sequences of the enzymes Xen1 and Xen2 are 95% identical with the same peroxidase activity, pH and temperature optimums, as well as thermostability, being approximately equal. The expression of peroxiredoxin 6 genes significantly differ during ontogenesis of X. laevis. The expression of xen1 starts on a later stage of development 47-48, while the gene xen2 is expressed on all stages of development with the same increase starting from stage 0-5. The level of xen2 expression in embryos increased after incubation in presence of hydrogen peroxide. The comparison of amino acid sequences of proteins Xen1 and Xen2 shows that only the enzyme Xen2 may have phospholipase activity, since it has residues of phospholipase A2 active center: Ser31, His25, Asp139. PMID- 22295573 TI - [The effect of semax and its C-end peptide PGP on expression of the neurotrophins and their receptors in the rat brain during incomplete global ischemia]. AB - Neurotrophins regulate key function of nervous tissue cells. Analysis of neurotrophins mRNA expression is an appropriate tool to assess therapeutic efficiency of the anti-stroke drugs. We have analyzed the effect of synthetic peptide semax and its C-terminal Pro-Gly-Pro tripeptide upon mRNAs expression of neurotrophins Ngf, Bdrf, Nt-3 and their receptors TrkA, TrkB, TrkC, p75 in rat frontal lobes, hippocampus and cerebellum after bilateral common carotid artery occlusion. The animals were decapitated 30 min, 1, 2, 4, 8, 12, 24 h after the operation. The mRNA expression of neurotrophins and their receptors was assessed by relative quantification using real-time RT-PCR. Our showed that ischemia causes a significant decrease in gene expression in the hippocampus. Semax and PGP affected the expression of neurotrophins and their receptors predominantly in the frontal cortex and hippocampus of the ischemized animals. In the frontal cortex, Semax treatment resulted in a decrease of mRNA level of receptors, while PGP treatment increased the level of these mRNA. Maximal neuroprotective effect of both peptides has been observed in the hippocampus 12 h after occlusion. A decrease of gene expression of neurotrophins and their receptors caused by the occlusion was overcome by Semax and PGP. These results clarify the semax mechanism of and present certain features of mRNA's expression of neurotrophins and their receptors in experimental conditions. PMID- 22295574 TI - [Modulation of activated oncogene c-kit expression with RNA-interference]. AB - Hyperexpression of oncogene c-kit is found in 80% patients with acute myeloid leukemia (AML). The transgenic model cell line expressing the oncogene c-kit was obtained by transduction with recombinant retrovirus. We have designed small interfering RNAs (siRNA) efficiently suppressing the expression of activated oncogene c-kit. Further small hairpin RNAs (shRNA) targeting c-kit mRNA were designed and expressed in lentiviral vectors. We report a stable reduction in c kit expression following the introduction of shRNAs into model cells as well as Kasumi-1 cells from the patient with AML. PMID- 22295575 TI - [Binding of human ribosomal protein S13 to the central domain of 18S rRNA]. AB - Human ribosomal protein S13 is a structural element of the small subunit of ribosome. It is a homologue of eubacterial ribosomal protein S15, and, besides, it possesses an extended N-terminal region, characteristic of the S15p family in eukaryotes and archaea. In the present study, we investigated binding of recombinant ribosomal protein S13 and its mutants containing deletions or substitutions of amino acid residues in different regions with an RNA transcript corresponding to a fragment of the central domain of 18S rRNA. We found that replacement of ultra-conservative residues H101 and D108 as well as deletions of either 29 C-terminal or 27 N-terminal residues substantially reduced affinity of the protein to the RNA transcript. Deletion of 54 C-terminal or 80 N-terminal residues completely deprived the protein of binding capacity. Using a footprinting assay, we identified sites in the RNA transcript changing their accessibilities to action of hydroxyl radicals under binding of either full length protein S13 or its mutant lacking 27 N-terminal residues. It is shown that these sites are located mainly in helix H22 of the 18S rRNA and in the region of its junction with helix H20 and are consistent predominantly with contacts of the rRNA with the conserved part of the protein. We concluded that binding of ribosomal protein S13 to 18S rRNA is provided mainly by conserved motifs of the protein corresponding to those motifs in its eubacterial homologue that are involved in the interaction with 16S rRNA in the 30S subunit. Role of the N terminal region of the protein in its binding to the central domain of 18S rRNA is discussed. PMID- 22295576 TI - [The influence of interdomain interaction on the amyloidogenic properties Bence Jones proteins]. AB - Isolated constant domains from two Bence-Jones proteins VAD and BIR able to form amyloid fibrils, whereas only the first of them to keep specific ability of the intact protein. Studies of conformation and stability of these proteins by scanning microcalorimetry, circular dichroism, fluorescence and analytical centrifugation at physiological conditions (10 mM phosphate buffer, pH 7.0, 100 mM NaCl) showed that the stability of isolated pair of constant domains (C(L) C(L)) VAD and BIR is reduced by compared with standard (nonamyloidogenic) Bence Jones protein. However, in the intact protein BIR stability of his constant domains increases sharply, which correlated with the loss of the protein ability to form amyloid fibrils. PMID- 22295577 TI - [The unusual thermodynamic properties of compact forms pFh fragments (hinge region) IgG3 Kuc and Sur]. AB - pFh fragments from the hinge region of human IgG3 Kuc and Sur can fold into compact form, resulting the formation of proteins with secondary (super secondary) structure, which is represented almost exclusively double poly-L proline helix. It was demonstrated by several methods that the thermal denaturation of compact form pFh fragment (hinge region) IgG3 Kuc and Sur occurs in two stages. The "two-state" model described the disintegration of the compact structure with preservation of the secondary structure (double poly-L-proline helix). In the second stage melts itself helix consisting of four cooperative units, which are formed by the sections with a high content of proline residues. Poliproline conformation of secondary structure and large number of disulfide bonds is responsible for high specific enthalpy of denaturation and high thermal stability. PMID- 22295579 TI - Physicians. Survey: residents hold the cards in job search. PMID- 22295578 TI - [GHL1-GHL15: new families of hypothetical glycoside hydrolases]. AB - Domains of fifteen recently found families of hypothetical glycoside hydrolases (GHL1-GHL15) have been used for iterative screening of the protein database. Evolutionary connections between representatives of these families were revealed. Also, their relationship with members of the following known families of protein domains were found: GH5, GH13, GH13_33, GH17, GH18, GH20, GH27, GH29, GH31, GH35, GH36A, GH36B, GH36C, GH36D, GH36E, GH36F, GH36G, GH36H, GH36J, GH36K, GH39, GH42, GH53, GH66, GH97, GH101, GH107, GH112, GH114, COG1082, COG1306, COG1649, COG2342, DUF3111, and PF00962. The unclassified homologues were grouped into 35 new families of hypothetical glycoside hydrolases: GHL16-GHL50. Position of GHL1 GHL15 families in the hierarchical classification of glycoside hydrolases and their homologues is discussed. Several new superfamilies of protein domains are suggested. PMID- 22295580 TI - HIPAA. Privacy, security enforcement actions on the increase. PMID- 22295581 TI - Patient care. Florida collaborative leads charge in reducing readmissions. PMID- 22295582 TI - Patient care. Experts: rethink mutritional needs of obese ICU patients. PMID- 22295583 TI - Technology. Mobile system aims to improve cardiac care. PMID- 22295584 TI - Air show calamity tests Reno hospital's preparedness. PMID- 22295585 TI - Infection prevention. Room design can play a critical role in improving patient safety. PMID- 22295586 TI - Because we know you're busy. PMID- 22295587 TI - Doubling down on the patient experience. AB - Medicare reimbursements will be based partly on HCAHPS scores beginning in 2013. Many hospitals are focusing on changing their organizational cultures to create what one executive calls "a standardized, excellent patient experience." PMID- 22295588 TI - Where are the specialists? AB - It's not just primary care physicians who are in short supply. Hospitals are using a variety of creative strategies to recruit certain hard-to-find specialists. PMID- 22295589 TI - The silver stampede. AB - Very soon a huge proportion of your patient population will be older than 65. That demands a vigorous focus on geriatric care both before and after discharge. PMID- 22295590 TI - Telemedicine: now it's a must. PMID- 22295591 TI - Strategic supply chain management. AB - A strategic focus on the supply chain can reap significant savings for hospitals. It also can improve employee satisfaction, patient safety and outcomes. PMID- 22295592 TI - Calling all rural hospitals to Phoenix. PMID- 22295593 TI - Awash in prescription meds. PMID- 22295594 TI - Gloves in arc flash: a big change in NFPA 70E. PMID- 22295595 TI - Overcoming gravity. PMID- 22295596 TI - Refuting the myths about resuscitation. PMID- 22295597 TI - Wireless detectors aiding emergency responders. PMID- 22295598 TI - Zero injuries is not your goal. PMID- 22295599 TI - The key to reducing EHS risks. PMID- 22295600 TI - Chemical plant security assessment; prioritizing facilities that need to be protected. PMID- 22295601 TI - Getting to zero. PMID- 22295602 TI - Using permanent electrical safety devices. PMID- 22295603 TI - The light of leadership. PMID- 22295604 TI - [Evaluation of environmental information disclosure by environmental agencies in China]. AB - Environmental information disclosure is seen as a creative approach in environmental governance worldwide. Environmental Information Disclosure Decree 2008 (EIDD) was regarded as a milestone of right-to-know and public participation in environmental protection in China. Environmental information disclosure can improve the intercommunication between the government and public, and also speed up the transition from conventional government-dominated environmental regulation to a more transparent and modern environmental governance system in China. Aiming to explore the effectiveness of EIDD implementation by environmental agencies, this study conducted the website interviews, the practical information disclosure requests, and telephone interviews with officers from environmental agencies in 31 provinces, 5 cities with independent budgetary status, and 27 provincial capital cities in 2010. It is concluded that the implementation of the Environmental Information Disclosure system has been improving over past two years but still far from being widespread, full and effective. The lack of enforcement and the ambiguity of some clauses in EIDD give environmental agencies great discretion to avoid disclosure and discourage enforcement of environmental information disclosure. PMID- 22295605 TI - [Spatial pattern evolution of carbon emission intensity from energy consumption in China]. AB - Using Theil index and spatial autocorrelation analysis methods, the characteristics, regional disparity and spatial pattern evolution of carbon emission intensity from energy consumption were analyzed on national, regional and provincial level from 1999 to 2007 in China. The results indicate that: (1) total energy carbon emission in China has increased from 0.91Gt in 1999 to 1.83Gt in 2007, while carbon emission intensity has decreased from 0.83 t x (10(4) yuan) (-1) to 0.79 t x (10(4) yuan) (-1); (2) carbon emission intensity of eight major economic blocks showed the trend of three-level differentiation, with that of northeast regions, the middle reaches of Yellow River regions and northwest regions above 1.0 t x (10(4) yuan)(-1); northern coastal regions, the middle reaches of Yangtze River regions and southwest regions 0.7-1.0 t x (10(4) yuan) ( 1); eastern and northern regions 0.32-0.51 t x (10(4) yuan) (-1); (3) Theil index analysis indicates that the within-region carbon emission intensities were similar, and the expanding total disparity of carbon emission intensity was primarily due to between-region inequalities. (4) spatial autocorrelation analysis shows that Global Moran's I has increased from 0.19 to 0.25, indicating that there were positive spatial correlations among provincial regions in China, and regions of similar carbon emission intensity agglomerated in space. The "cold spot" areas of carbon emission intensity were relatively stable, while the "hot spot" areas has gradually shifted from northwest regions to the middle reaches of Yellow River regions and northeast regions. (5) spatial disparity of carbon emission intensity is closely related to factors such as regional resources endowment, economic development, industrial structure and energy utilization efficiency. The study of regional disparity and spatial autocorrelation provides insight into spatial heterogeneity and spatial pattern evolution of carbon emission intensity in China, and also provides references for the development of differential regional objectives of carbon emission reduction and related regulation policies. PMID- 22295606 TI - [Effect of weather condition on the aerosol scattering property at Shangdianzi]. AB - A study on the effect of weather condition on the aerosol scattering property has been carried out using one year measurement data sets of aerosol scattering coefficient (ASC) and meteorological parameters at Shangdianzi (SDZ). The results showed that the ASC was highest in haze-fog day with 608.4 Mm(-1) and higher in fog day with 500.6 Mm(-1) and haze day with 423.7 Mm (-1) those were 6.4-9.2 times higher than the ASC in normal day. The ASC was highest in summer in all kinds of weather conditions. The lower ASC in fog day and haze-fog day was observed in autumn and winter, respectively. There was no evident difference of the ASC between other three seasons in haze day and normal day. Pronounced seasonal variation of the mass scattering efficiency (MSE) of PM2.5 was observed in fog day with the highest value in summer. Significant diurnal variations in ASC were observed in haze-fog day and normal day with a unimodal pattern and a bimodal pattern, respectively. The wind was the most important factor for the ASC at SDZ. The transport of aerosol particles by the strong southwest wind should be responsible for the higher level of ASC in SDZ area and regional scale in low visibility weather conditions. The northeast wind was favourable to the reduction of ASC, especially in normal day. PMID- 22295607 TI - [Pollution characteristics and source of the atmospheric fine particles and secondary inorganic compounds at Mount Dinghu in autumn season]. AB - Real-time measurements of PM2.5, secondary inorganic compounds in PM2.5 (SO4(2-), NH4(+), and NO3(-)) and related gaseous pollutants were conducted at Mount Dinghu, a regional background station of the Pearl River Delta (PRD), in October and November 2008 by using a conventional R&P TEOM and a system of rapid collection of fine particles and ion chromatography (RCFP-IC). Sources and transportation of atmospheric particles during the experiment were discussed with principal component analysis and backward trajectories calculated using HYSPLIT model. The average daily mass concentrations of PM2.5 were 76.9 microg x m(-3) during sampling period, and average daily mass concentrations of SO4(2-), NH4(+), and NO3(-) were 20.0 microg x m(-3), 6.8 microg x m(-3) and 2.6 microg x m(-3), respectively. The sum of these three secondary inorganic compounds accounted for more than one third of the PM2.5 mass concentration, which had become the major source of atmospheric fine particles at Mount Dinghu. The diurnal variation of PM2.5, SO4(2-), and NH4(+) all showed a "bimodal" distribution with two peaks appeared at 10:00 am and at 16:00 pm, respectively, whereas NO3(-s) howed "single peak" distribution peaked at 10:00 am. The mass concentrations of SO4(2-) in PM2.5 had the similar diurnal variation with that of SO2, SO4(2-) in PM2.5 was mainly transformed from SO2, whereas NO3(-) showed difference diurnal variation with that of NO2, and the second conversion rate of NO2 was far lower than that of SO2. NH4(+) in PM2.5 existed mainly in the form of sulfate, nitrate and chloride. Both of principal component analysis and back trajectory analysis showed that the variations of PM2.5 and secondary inorganic compounds at Mount Dinghu were mainly affected by the long-range transport air mass passed over Guangzhou, Huizhou and other highly industrialized areas which carried air pollutants to the observation site, at the same time local sulfate originated from secondary formation also contributed an important part of atmospheric fine particles and the contribution from local direct emission was little. PMID- 22295608 TI - [Soil respiration variations in winter wheat field in different previous crops and its influencing factors]. AB - This study was to define the Variations of soil respiration, the response of influence factors to soil respiration and carbon sink in the total growing season, in winter wheat field of different previous crops. The results showed that: (1) as soil depth increases, the response of temperature to soil respiration rate also increased with a lag; (2) the soil respiration rate was quadric to soil moisture, phosphorus, potassium, soil urease activity, soil temperature, soil moisture as the main factors had an effect on soil respiration rate; soil temperature had the stronger effect on soil respiration rate when potassium had the weaker effect on soil respiration rate; (3) the average carbon emission rate in wheat filed of different previous crops showed as follow: Pepper of previous crops > celery of previous crops > corn of previous crops > eggplant of previous crops. The intensity of carbon "sink" displayed as follow: eggplant of previous crops > celery of previous crops > corn of previous crops > pepper of previous crops. As for the trials of this study, although the soil respiration rate is highest in the winter wheat filed of previous pepper, the amount of carbon fixed is the most. Its ratio of net primary productivity (NPP) and soil carbon release quantity was highest, so carbon sink was the strongest. If rotation planting was arranged according to the purpose of increasing carbon sink and reducing carbon emissions, pepper was relatively appropriate stubbles crop, followed by corn crop, celery and eggplant. PMID- 22295609 TI - [Effects of nitrogen fertilization, soil moisture and soil temperature on soil respiration during summer fallow season]. AB - On the loess plateau, summer fallow season is a hot rainy time with intensive soil microbe activities. To evaluate the response of soil respiration to soil moisture, temperature, and N fertilization during this period is helpful for a deep understanding about the temporal and spatial variability of soil respiration and its impact factors, then a field experiment was conducted in the Changwu State Key Agro-Ecological Experimental Station, Shaanxi, China. The experiment included five N application rates: unfertilized 0 (N0), 45 (N45), 90 (N90), 135(N135), and 180 (N180) kg x hm(-2). The results showed that at the fallow stage, soil respiration rate significantly enhanced from 1.24 to 1.91 micromol x (m2 x s)(-1) and the average of soil respiration during this period [6.20 g x (m2 x d)(-1)] was close to the growing season [6.95 g x (m2 x d)(-1)]. The bivariate model of soil respiration with soil water and soil temperature was better than the single-variable model, but not so well as the three-factor model when explaining the actual changes of soil respiration. Nitrogen fertilization alone accounted for 8% of the variation soil respiration. Unlike the single-variable model, the results could provide crucial information for further research of multiple factors on soil respiration and its simulation. PMID- 22295610 TI - [Investigation of heterotrophic and autotrophic components of soil respiration in a secondary forest in subtropical China]. AB - Trenched plots were set up in 2010 in a secondary forest in subtropical China, in order to investigate the seasonal variations of soil respiration (R(s)) and heterotrophic respiration (R(h)). Autotrophic respiration (R(a)) was estimated to be the difference between R(s) and R(h). Soil temperature and moisture were simultaneously measured during respiration measurements. Results indicated that R(s) and R(h) showed the similar seasonal variations. Seasonal mean rates for R(s), R(h) and R(a) were 3.42, 2.36 and 1.06 micromol x (m2 x s)(-1), respectively. Regression analysis indicated that R(h) increased with the increase of R(s); an natural logistic equation could be employed to explained the relationship between R(h) (y) and R(s) (x). Approximately 90.5% (R2 = 0.905) variations in R(h) could be explained by the equation. Apparent exponential relationships of R(h) and R(a) with soil temperature existed, but differed from each other and from the relationship for R(s). The exponential equations explained about 78.4%, 76.4% and 65.6% variations in R(s), R(h) and R(a), respectively, with the P values less than 0.01. The Q10 values for R(s), R(h) and R(a) were 1.97, 1.76 and 3.31, respectively. It was indicated that, seasonally, R(h) and R(a) represented 69% and 31% of R(s). R(a) showed significantly higher temperature sensitivity than R(h). PMID- 22295611 TI - [Mitigation of nitrous oxide emissions in vegetable system by treating soil with dicyandiamide, a nitrification inhibitor]. AB - Undisturbed soil monolith lysimeter was used to investigate the effectiveness of DCD (dicyandiamide) in reducing N2O emissions in vegetable (Chinese cabbage and pepper) field. Results showed that DCD significantly reduced total N2O emission in vegetable field. Total N2O emissions from the urea treatment without DCD reached 0.215 kg x hm(-2) for Chinese cabbage, and it reduced to 0.109 kg x hm( 2), equivalent to a 49.3% reduction. The total N2O emissions for pepper were much higher compared with those for Chinese cabbage. The total N2O emitted from the urea treatment was 2.32 kg x hm(-2) (without DCD) and it was reduced to 1.14 kg x hm(-2) with DCD application, representing a 50.9% reduction. In the control treatments where no urea was applied, the daily N2O flux was very low and it never exceeded 9 microg x (m2 x h) (-1) for Chinese cabbage and 22 microg x (m2 x h) (-1) for pepper, respectively, but DCD also reduced N2O emissions (33.5% for Chinese cabbage and 33.4% for pepper). In addition, the urea-N emission factor (EF) was 0.15%, 0.99% for Chinese cabbage and pepper without DCD, respectively, and it was reduced to 0.07%, 0.52% when DCD was applied. These results demonstrated the potential of using nitrification inhibitors (DCD) to mitigate N2O emissions in vegetable system. PMID- 22295612 TI - [Multiple pattern inverse water quality modeling approach for predicting the water quality consequence of Lake Chenghai water elevation control]. AB - A water quality model was developed through incorporating the water surface elevation and water quality data of Lake Chenghai into the CE-QUAL-W2 computational platform. The model integrates the water surface elevation and water quality into a holistic dynamic system based on the data of Lake Chenghai, and was calibrated against observed data using a multiple pattern inverse water quality modeling technology, which was driven by a robust genetic algorithm (GA). After the model was calibrated, it was used to produce robust predictions of the lake water quality in response to various water elevation controlled scenarios. The model established a basis for quantifying the water quality responses under uncertainty, and is valuable for supporting effective and reliable management decision making. The results of this research suggest that various water elevation control scenarios only result in insignificant water quality improvement in terms of TN, TP, and COD concentrations, therefore, it does not recommend to consider water elevation control to be the major water quality management option for Lake Chenghai. PMID- 22295613 TI - [An integrated eutrophication assessment for lakes and reservoirs]. AB - An integrated eutrophication assessment framework is developed for lakes and reservoirs based on an ecogeographical classification method and an artificial neural network model. Using the USEPA Nutrient Criteria Database as the basic reference and considering the ecogeographical characteristics of Chinese lakes and reservoirs, a simple eutrophication assessment criterion considering the ecogeographical characteristics is proposed for the first time. This criterion places the emphasis on the determination of critical values of key parameters for various regions. Moreover, an artificial neural network (ANN) assessment model is developed, considering the complexity and nonlinearity of eutrophication process. It is found that this ANN assessment model offers the advantage to assess with more accuracy the trophic status in nitrogen-limited water bodies. Integrating such two assessment methods can establish a simple but general eutrophication assessment framework; verification with 30 lakes and reservoirs shows that it can be served as a reliable and cost-effective tool for aquatic environmental management. PMID- 22295614 TI - [Retrieving for chlorophyll-a concentration and suspended substance concentration based on HJ-1A HIS image]. AB - Based on geometry correction using ERDAS software and radiation correction using 6S model for HJ-1A hyper-spectrum image (HSI) on May 2 in 2010 and the analysis of spectrum for water data and spectral data of hyper-spectrum image, this paper processes original spectrum data of 28 sample points using method of normalization and method of first-order derivation. Single-band and band combination are selected to establish inversion models of the concentration of chlorophyll-a and solid suspensions. Choosing the model with biggest correlation coefficient, the spatial distribution map of the concentration of chlorophyll-a and solid suspensions content in Taihu Lake is acquired. The research results show: Band-73 of hyper-spectrum image which has been normalized shows the biggest correlation coefficient of the concentration of chlorophyll-a, remote sensing sediment parameter shows the biggest correlation coefficient of the concentration of solid suspensions, the result is consistent with analysis of spectral data of hyper-spectrum image. Average relative errors of predicted and measured values are within 30 percent. Spatial distribution map of water quality is consistent with the result of field surveys. Therefore, based on reference of the analysis of sensitive band of spectrum for water data, HJ-1A hyper-spectrum image can give quantitative estimation of water quality parameters in Taihu Lake. PMID- 22295615 TI - [Early growth of phytoplankton community in Dianshan Lake]. AB - Seasonal variation of phytoplankton community biomass (Chla) in Dianshan Lake was simulated based on data of 2004-2009. The result showed that early growths of the phytoplankton community in spring and summer seasons could be well described by the Logistic growth model. General speaking, phytoplankton community dominated by diatom and green algae may enter its exponential phase in the late February, doubling its density within 18 days, and reaching its maximum growth rate of 29.4 microg x (L x month) (-1) in the middle of March, blooming in June. Phytoplankton community dominated by blue green algae may enter its exponential phase in the middle June, doubling its density within 26 days, and reaching its maximum growth rate of 22.8 microg x (L x month) (-1) in the middle of July, blooming during August-September. The general pattern of early growth of phytoplankton community may offer sound information for early warning and prevention of algal bloom. PMID- 22295616 TI - [Prelimary study of TFA in surface water of some cities over China]. AB - Trifluoroacetic acid (TFA) is a stable organic pollutant with potential toxicity. The accumulation of TFA in water environment results in elevated concentration and also leads to ecological health risk. In this study, a total of 43 water samples, including tap water and surface water, were collected in 16 cities all over China. TFA in these water samples was pretreated through derivatization and analyzed by Gas Chromatography equipped with Mass Spectroscopy Detector. The results showed TFA was detectable in all water samples ranged from 13.7 ng x L( 1) to 7 850 ng x L(-1), and the values notably varied from city to city. Shanghai had the highest TFA concentration, with 3 054 ng x L(-1) in tap water and 7 850 ng x L(-1) in river water respectively. Spatial distribution analysis displayed that several areas in eastern China, like Shanghai, Anhui province, and Yantai in Shandong province, had relatively higher TFA concentrations as compared to other cities. The fluorochemical industrial area centralizes in eastern China, from which the direct or indirect emission of fluorochemicals as a source of TFA likely resulted in higher TFA concentrations in water environment in relevant areas. PMID- 22295617 TI - [Preliminary results concerning summer-time denitrification in the Jiulong River Estuary]. AB - Denitrification is an important process mitigating nitrogen (N) pollution in aquatic systems. Water samples in 13 sites throughout the Jiulong River Estuary were collected in July, 2010 in a preliminary investigation of the denitrification rate in this area. As end-products of denitrification, dissolved N2 was measured by determining N2 : Ar ratios using MIMS (HPR-40), while the concentration of nitrous oxide (N2O) dissolved in water was determined by Purge and Trap-Gas Chromatography. The results showed significant spatial variance of net increase of dissolved N2 (ranging between - 9.9 and 66.8 micromol x L(-1)) and N2O (ranging between 4.3 and 31.5 nmol x L(-1)) in the Jiulong River Estuary. The net increase of dissolved N2 and N2O declined gradually from river sites to sea sites. Dissolved N2O was supersaturated by 170%-562%. The air-water fluxes of N2 ranged between -2.9 and 53.2 mmol x (m2 x d) (-1), and N2O between 5.2 and 23.9 micromol x (m2 x d)(-1). The N2O yield shared only 0.03% - 1.2% (average 0.25%) of total N air-water flux. The results suggested that water temperature and nutrient (N and P) were the key factors influencing denitrification. The denitrification rate is controlled by nitrate level at fresh-water sites with salinity < 0.5%. However, in salty waters, net increase in N2 and N2O mainly originated from denitrification occurring upstream of the estuary, and was dominated by the salinity gradient due to tidal mixing. PMID- 22295618 TI - [Research on the reasons of red water in a southern city in China]. AB - The red water in the drinking distribution systems of a southern city was investigated by analysing the water quality, such as DO, residual chlorine, iron, manganese, iron bacteria and ammonia-oxidizing bacteria. The objectives of this study were to identify the reasons of red water with the aim to supply the answer to this problem. The results showed that the main compositions of the deposits were iron and manganese. There were manganese overstep (the maximum of Mn could reach to 0.33 mg x L(-1)) in the plant effluent with Larson ratios > 1 and the significant difference in water quantity, sulfate and electrical conductivity among the four plants. The density of the iron bacteria and ammonia-oxidizing bacteria (10(0)-10(3) MPN x mL(-1)) was high. The potential reason for the red water was the water corrosion of plant effluent. Secondly, the red water easily occurred in the distribution systems with lower DO and residual chlorine. In addition, serious nitrification caused microbiological corrosion was another vital reason. According to the research, the primary methods for controlling red water were proposed. PMID- 22295619 TI - [Method of ecological risk assessment for risk pollutants under short-term and high dose exposure in water pollution accident]. AB - In recent years, water pollution accidents resulting in acute aquatic ecological risk and security issues become a research focus. However, in our country, the surface water quality standards and drinking water health standards were used to determine the safety of waters or not in pollution incidents due to lacking safety effect threshold or risk value for protection of aquatic life. In foreign countries, although predicted no effect concentration (PNEC) or risk value (R) of pollutants were provided for protection of aquatic organisms, the PNECs or risk values were derived based on long-term exposure toxicity data NOECs (no observed effect concentrations) and lack of short-term exposure risk or threshold values. For the short-term and high dose exposure in pollution incident, ecological risk assessment methods were discussed according to the procedures of the conventional ecological risk assessment and the water quality criteria establishment of the U.S. EPA for the protection of aquatic organisms in short-term exposure, and had a case study. At the same time, we provide some suggestions for the establishment of ecological risk assessment system in water pollution incidents. PMID- 22295620 TI - [Spatial and temporal variability of nitrate contaminant in groundwater in Jinfo Mt. area, Chongqing, China]. AB - The geochemical background of nitrate in groundwater in Jinfo Mt. area was determined, and spatial and temporal variability of nitrate contaminant was analyzed using geochemical, statistical and GIS methods. Twenty-three samples were collected from groundwater discharge points in the study area during 1976 1977, 2004-2006 and 2009, and mass concentration of nitrate in groundwater was tested. The results showed that the geochemical background of nitrate in groundwater in study area was in the range of 0.72-2. 00 mg x L(-1), and the threshold of anomaly was 3.20 mg x L(-1). During 2004-2006 and 2009, the average values of nitrate concentration in groundwater in Jinfo Mt. natural reserve were 2.08, 2.67, 2.59 and 3.92 mg x L(-1); and were 39.08, 25.46, 17.99 and 13.73 mg x L(-1) in the groundwater out of the reserve; the average over-limit rates (standard limit NO3(-) -N < or = 10mg x L(-1)) were 451.64%, 478.61%, 331.85% and 145.67%; the maximum over-limit rates were 1 475.81%, 1 080.39%, 538.20% and 361.78%. Results of interpolation showed that the high value centers of nitrate concentration in groundwater in study area were changing over time, but districts with low nitrate concentration in groundwater in study area were distributed along Jinfo Mt. natural reserve. The application of environmental policy measures and industrial restructuring implemented were reasonable and successful, which had a positive effect to environmental protection. PMID- 22295621 TI - [Spatial and temporal variations of phosphorus forms in surface sediments of Chaohu Lake]. AB - Total phosphorus (TP), inorganic-phosphorus(IP), organic-phosphorus (OP), Fe/Al bound phosphorus (NaOH-P) and Ca-bound phosphorus (HCl-P) in surface sediments of Chaohu Lake were measured, using the standard measurement and test (SMT) procedure of phosphorus forms in freshwater sediments. ArcGIS 9.2 and goestatistics software GS + 5. 3 were applied to process the spatial data and interpolation. Results showed that no significant seasonal variation of TN, TP and organic matter contents in sediments were presented, and the western lake had higher contents of TN, TP and organic matter than those in eastern lake; the C/N ratios varied from 21.35 to 28.19, with average value of 24.94, which demonstrated the dominance of non-point source pollution. The TP contents in surface sediments ranged from 528.90 to 1 385.71 mg x kg(-1), and the main form of TP in sediments was IP(accounted for 55.78% -79.86% of TP). The OP in sediments ranged from 169.05 mg x kg(-1) to 841.24 mg x kg(-1), with eastern lake and western lake were 376.02 mg x kg(-1) and 406.53 mg x kg(-1), respectively (accounted for 47.49% and 36.28% of TP); the NaOH-P contents in sediments ranged from 33.77 mg x kg(-1) to 411.37 mg x kg(-1), with eastern lake and western lake of 376.02 mg x kg(-1) and 406.53 mg x kg(-1), respectively (accounted for 21.73% and 33.12% of the IP); the HCl-P contents ranged from 194.95 mg x kg(-1) to 477.45 mg x kg(-1), with eastern lake and western lake 321.71 mg x kg(-1). and 338.08 mg x kg(-1), respectively (accounted for 64.50% and 40.53% of the IP), which was the main species of IP. The OP contents was high in spring and winter compared with summer and autumn, while the contents of HCl-P and NaOH-P in summer and autumn were higher than those in spring and winter. PMID- 22295622 TI - [Mineral and elemental characteristics of microparticles with different size fraction in snowpits from Zadang Glacier]. AB - In order to study the mineral and elemental composition of insoluble microparticles (IP) in snow/ice, two snowpits were collected from the Zadang Glacier in Mt. Nyainqentanglha (30.47 degrees N, 90. 65 degrees E, 5 800 m a. s. l) in May and July, 2009, and IP samples were investigated. The measurements of mineral composition with different size fractions (d > 10 microm and 0.22 microm < d < 10 microm) were carried out using Particle-induced X-ray emission (PIXE) and X-ray diffraction analysis (XRD). The main mineral components of both coarse and fine IP are quartz, mica and calcite, accounting for 71.5% and 76.5%, respectively. The crustal elements concentrations (e.g. Si, Al, Fe, K, Mg and Ca) are 97% and 85.1% of total coarse/fine IP, while S, Cl and P take fairly proportion in fine microparticles (d < 10 microm). Seasonal variability of mineral composition in coarse microparticles (d >10 microm) is not obviously; However it's significantly in fine IP. Enrichment factors (EF) analysis reveals that several elements (e.g. Sc, P, Cr, S and Cl) in fine IP during monsoon season have high values which indicate these elements may be influenced by anthropogenic activities. Backward air mass trajectory analysis suggests that air masses in this region mainly originate from the South Asia areas during monsoon season, and air masses mainly come from arid/semi-arid region in the South and West Asia during non-monsoon season. Therefore, anthropogenic pollutants from the South Asia may be transported by the summer Indian monsoon to the Zadang glacier area. The coarse IP may derive from the local or remote mineral dust, and chemical compositions of fine IP interfere with anthropogenic pollutants. PMID- 22295623 TI - [Correlations between PBDEs and thyroid hormone concentrations in adults from production source area]. AB - Polybrominated diphenyl ethers (PBDEs) concentrations in 36 resident serum samples from PBDEs production source area were analyzed by gas chromatography/negative chemical ionization/mass spectrometry(GC-NCI-MS) method, and the concentrations of thyroid hormones were determined as well. The sigma5PBDEs (BDE-28, -47, -153, -183, -209) concentrations(lipid weight) in serum ranged from 130.3 to 4 478.4 ng x g(-1), with an average value of 529.9 ng x g( 1). BDE-209 was a dominant PBDE congener, on average accounting for 69.8% of the total PBDEs concentrations. Spearman rank correlation coefficient was calculated between PBDEs and thyroid hormone, it showed that there were high significant negative correlation between BDE-28, -47, -153, -183 and thyroid-stimulating hormone (TSH), and significant negative correlation was also found between BDE 183 and free thyroxine (fT4). Additionally, there were significant positive correlation between BDE-28, -47 and triiodothyronine (T3), as well as between BDE 28, -153, -183 and free triiodothyronine(fT3). In summary, the concentrations of PBDEs in serum in this study were at a high level, and BDE-209 was the predominant congener. The exposure to the PBDEs may affect thyroid hormone levels, and the further research should focus on the relationship between PBDEs and thyroid hormone concentrations. PMID- 22295624 TI - [Characteristics of PCBs in a capacitor storage site and an industrial brownfield]. AB - The levels and congener patterns of 28 PCBs compounds were investigated in soil and dust fallout collected in a capacitor storage site and an industrial brownfield, respectively in Sichuan Ziyang Locomotive Factory. The highest concentration of the total PCBs(sigma PCBs =227 502 ng x g(-1)) was found in soil collected from the front gate (unsealed) of the capacitor storage tunnel. Very high levels of sigma PCBs, exceed 10 microg x g(-1), were also found in the dust collected from the window sill of an iron foundry. There were significant positive correlations (P < 0.01) among PCB congener concentration in the storage site and the iron foundry samples. The major contribution to the total content of PCBs in the high contaminated samples was tetrachlorinated biphenyls, followed by tri- and penta-chlorinated biphenyls. Hexa- and higher chlorinated biphenyls contributed more to sigma PCBs in the iron foundry than those in the storage site. The total toxicity equivalents (TEQ) of 12 dioxin-like congeners varied in the range of 75.43-24 027 pg x g(-1) and were much higher than those in soils of e-waste recycling sites. However, PCB126 contribute the most to the TEQ in most cases. PMID- 22295625 TI - [Distribution and sources of oxygen and sulfur heterocyclic aromatic compounds in surface soil of Beijing, China]. AB - 62 surface soil samples were collected from different environmental function zones in Beijing. Sulfur and oxygen heterocyclic aromatic compounds were detected by GC/MS. The objectives of this study were to identify the composition and distribution of these compounds, and discuss their sources. The results showed that the oxygen and sulfur heterocyclic aromatic compounds in the surface soils mainly contained dibenzofuran, methyl- and C2-dibenzofuran series, dibenzothiophene, methyl-, C2- and C3-dibenzothiophene series and benzonaphthothiophene series. The composition and distribution of the oxygen and sulfur heterocyclic aromatic compounds in the surface soil samples varied in the different environmental function zones, of which some factories and the urban area received oxygen and sulfur heterocyclic aromatic compounds most seriously. In Beijing, the degree of contamination by oxygen and sulfur heterocyclic aromatic compounds in the north surface soil was higher than that in the south. There were preferable linear correlations between the concentration of dibenzofuran series and fluorene series, as well as the concentration of dibenzothiophene series and dibenzofuran series. The oxygen and sulfur heterocyclic aromatic compounds in the surface soil were mainly derived from combustion products of oil and coal and direct input of mineral oil, etc. There were some variations in pollution sources of different environmental function zones. PMID- 22295626 TI - [Distribution, sources and ecological risk assessment of organochlorine pesticides and polychlorinated biphenyl residues in surface sediment from Dahuofang Reservoir, Liaoning]. AB - Twenty-four surface sediment samples collected in Dahuofang Reservoir were analyzed for organochlorine pesticides (OCPs) and polychlorinated biphenyl(PCBs) residues. The results showed that the recent occurrence levels in sediments were 0.70-3.48 ng x g(-1)(with a mean of 1.58 ng x g(-1) +/- 0.71 ng x g(-1) for HCHs, 0.85-4.94 ng x g(-1) (1.94 ng x g(-1) +/- 0.82 ng x g(-1)) for DDTs, 1.46-3.52 ng x g(-1) (2.42 ng x g(-1) +/- 0.64 ng x g(-1)) for PCBs. The inputs of OCPs and PCBs could be attributed to the recent use of relevant products and the heavy historical application which preserved in agricultural soil in adjacent area. Contamination level of OCPs and PCBs in surface sediments decreased from upstream to downstream, and samples of higher contamination level were located in Hunhe river mouth, both of which indicated distribution of OCPs and PCBs in reservoir was influenced by riverine discharge. The ecological risk assessment suggested that the OCPs in the sediments of the study area might pose a bit high harm to the environment, while PCBs might pose little harm to the environment. PMID- 22295627 TI - [Normal alkanes characteristic parameters of Jinzhou Bay surface sediments]. AB - The concentration, composition and characteristic parameters of 18 surface sediment samples collected from Jinzhou Bay were studied. The samples were soxhlet-extracted with a mixture of 1: 1 (V/V) dichloromethane-hexane and analyzed by GC-MS after purification and concentration. Concentrations of n alkanes vary from 1.9 to 4.2 microg x g(-1) with an average value of 2.6 microg x g(-1) dry weight. n-Alkanes distribution patterns of all positions were characterized by double peak-cluster, which means double sources from terrestrial and marine origin. The sum of nC25 to nC31 accounts for 20%-32% of the total n alkanes, while the average value of L/H, C31/C19, TAR ratio are 0.67, 3.06, 2.02, respectively. All of these three indices suggest that the terrestrial contributions are higher than marine sources, especially for No. 2, 3 and 7 stations, which were influenced by riverinput nearby. Carbon Preference Index (CPI) ranges from 1.19 to 2.63 with an average value of 1.73, which is close to 1; the ratio of Pristane/Phytane (Pr/Ph) and unresolved/resolved compounds (U/R) range from 0.91 to 1.28, 2.2 to 4.3, respectively. All of these three parameters indicate that No. 13 and 15 stations are influenced by petroleum pollution. Comprehensive analysis of various parameters shows that Jinzhou Bay is threatened by both terrestrial inputs and petroleum hydrocarbons contaminations, which may relate to river discharging and port shipping in Jinzhou Bay. PMID- 22295628 TI - [Distribution characteristic and bioaccessibility of lead in kindergarten dust of Wuhan City]. AB - The characteristics of lead pollution and the associated health risk of children for the dust samples from 69 representative kindergartens in different type districts of Wuhan were investigated. Total lead concentration and bioaccessibility according to physiologically based extraction test (PBET) were determined. Results showed that the levels of lead concentration in dust ranged from 36.3 to 1 523 mg x kg(-1) with an average value of 169 mg x kg(-1), lower than published data from other areas. The great spatial variation of Pb in dust indicated that specific sites have been seriously contaminated by Pb. The bioaccessibilities of Pb in dusts were 35% +/- 15% at gastric phases and 7.6% +/- 5.8% at intestinal phases. According to the predicted model with the Integration Exposure Uptake Biokinetic Model (IEUBK), the geometric mean blood lead of children (0-6 years) was 2.73 microg x dL(-1), of which over 10 microg x dL(-1) was less than 0.001% and exceeded 5 microg x dL(-1) was 3.32%. PMID- 22295629 TI - [Pollution of agricultural soils by a wastewater outflow from a metal smelter in Guangxi Zhuang autonomous region]. AB - Pollution characteristics of heavy metals in the farmland soil nearby a metal smelter were studied. Soil samples were collected and the contents of elements V, Cr, Mn, Co, Ni, Cu, Zn, Rb, Sr, Mo, Cd, Sn, Sb, Pb, U and As in the bulk samples of soil profiles were measured, with the objectives to identify the pollution status and pollution characteristics of the farmland soil that were suffered from smelter effluents flooding, an acute pollution accident. The results indicate that the concentrations of heavy metals Zn, Mn, As, Pb, Cd,Sb in the soil were 113.28-212.22, 251.67-2 429.29, 34.44-130.28, 50.63-544.74, 63.44-317.33, 39.41 551.17 mg/kg, respectively, higher than the background level. These polluted soils not only have high concentrations of As, but also of the Zn, Mn, Pb, Cd and Sb. According to correlation analysis, pollution level is closely with local nonferrous metal exploitation, and principal pollutants have the same source. Some trace metals, such as Zn, Cr, Cd, show increasing concentration first and then decreasing trend in the soil profile. Soil acidification appears in the topsoil. This study has characterized the metal pollution in soils flooded by sudden smelting effluents spilling, and provided a theory base for pollution treatment. PMID- 22295630 TI - [Laboratory simulation study on the influence of resuspension on the release of mercury from Yangtze estuarine tidal flat]. AB - Using a Particle Environment Simulator, laboratory simulation experiment on the influence of resuspension on the release of mercury from sediments collected from medium tidal flat and low tidal flat in Chongming Dongtan was conducted. Results indicated that the conditions of overlying water changed significantly during resuspension. The concentrations of HgD and HgP were mainly in the rang of 0.152 2.657 microg x L(-1), 0.080-2.722 microg x L(-1) separately. In the resuspension processes, mercury was released from the medium intertidal sediments under the salinity condition of 4.1 per thousand, 8.0 per thousand, 10.0 per thousand, 13.0 per thousand, and from the low intertidal sediments under the salinity condition of 13.0 per thousand. However, the release of mercury from the medium intertidal sediments is not significant under the salinity condition of 4.1 per thousand, 8.0 per thousand, 10.0 per thousand. The salinity of overlying water had an important effect on resuspension. In different salinity condition, the release of mercury was different. And the release of mercury from medium tidal flat and low tidal flat was different during the resuspension periods, the release of mercury from the medium intertidal sediment was significantly higher than the release from the low intertidal sediment. When the rotate speed was (210 +/- 5) r x min( 1), the desorption of mercury significantly increased, thereby the rotate speed had an effect on the release of mercury. PMID- 22295631 TI - [Effect of surfactant on sorption behaviors of DDT on Jiaozhou Bay sediment]. AB - A batch sorption study was carried out to investigate the sorption behaviors of DDT onto JiaoZhou Bay sediment in the presence of an anionic surfactant sodium dodecylbenzene sulfonate (SDBS), and a cationic surfactant, cetyltrimethylammonium bromide (CTAB) with low concentrations. The results indicated that the sorption process followed the pseudo-second-order model and the sorption systems could be well described by the Freundlich type. Within the investigated concentrations of CTAB and SDBS, both SDBS and CTAB increased the sorption of DDT to sediment. The sorption rate and capacity increased with increasing SDBS and CTAB concentrations, and CTAB showed a significant impact. Take p ,p'-DDT as an example, the sorption rate constant increased from 1.232 x 10(-2) g x (microg x min)(-1) to 4.193 x 10(-2) g x (microg x min)(-1) and the Freundlich coefficient increased from 2.866 (microg x g(-1)) (L x microg( 1))(1/n) to 7.932 (microg x g(-1)) (L x microg(-1))(1/n) when the SDBS concentration was 10 mg x L(-1). The influence of temperature on sorption of DDT in the presence of SDBS was also studied. Within the temperature range of 283-308 K, lower temperature had a positive effect on the sorption. The thermodynamic parameters showed that the sorption was spontaneous and exothermic, and the randomness was increased during the process. Furthermore, the presence of SDBS caused lower deltaG0, deltaH0 and deltaS0 values. This study provided theoretical foundation for migration, transformation and fate of DDT in Jiaozhou Bay sediment. PMID- 22295632 TI - [Absorption characteristics of molybdenum by reed and cattail]. AB - The adsorption characteristics of reed and cattail to molybdenum were studied. The toxicity, removal rate, adsorption process and accumulation of Mo were investigated in the short-term indoor-culture experiment. The effects of Mo adsorbed by two plants in nutrition solution with different concentrations were also studied. Due to the Mo toxicity, the color of stems and leaves of two plants had become scorch and the transpiration was declined. The cattail illustrated higher tolerance to Mo than reed when Mo concentration was in the range of 2-20 mg x L(-1). The removal rate of Mo by cattail was 87%, which was higher than reed (62%) with Mo concentration of 2 mg x L(-1). The absorption process of Mo by two plants was homeostasis, and the passivity absorption was the main absorption mechanism. Mo enrichment amount in cattail was higher than that in reed, and Mo concentration in shoot were higher than that in roots. The results displayed that cattail was Mo hyper accumulator. The absorption of Mo was not enhanced with the increase of nutrition solution concentration, due to the competition of other ions. The study suggested that the absorption capacity of Mo was significant by the two plants, and cattail was better for Mo removal than reed. PMID- 22295633 TI - [Cation exchanges during the process of Cd(2+) absorption by Alfalfa in aqueous solutions]. AB - A hydroponic experiment was conducted to investigate the cation exchanges during the process of Cd2+ absorption by Alfalfa in aqueous solution. The absorption efficiency of Alfalfa plants with 0-10 mg x L(-1) Cd2+ treatments, changes of Na+, K+, Mg2+, Ca2+ and NH4(+) concentration, and the variation of pH values at different absorption time (0, 1, 2, 4, 8, 12, 24 and 72 h) were studied separately. The multiple linear regressions between Cd2+ absorption and cation variation were analyzed. The results indicated that when Cd2+ concentrations were 0.1, 1, 5, 10 mg x L(-1), the absorption efficiencies of Cd2+ by Alfalfa after 72 h were 85.86%, 52.14%, 15.97% and 7.81%. Cation exchange was involved in the removal of Cd2+ by Alfalfa in aqueous solution. Except for NH4(+), the concentrations of cationic metals Na+, K+, Mg2+ and Ca2+ in aqueous solution increased over time, which increased 11.30% - 61.72%, 21.44% - 98.73%, 24.09% - 8.90% and 37.04% - 191.96%, respectively. Kinetic studies illuminated that the release of Na+, K+, Mg2+ and Ca2+ by Alfalfa in Cd2+ solution with initial concentrations of 0, 0. 1, 1, 5, 10 mg x L(-1) best fitted pseudo-second-order equation,while the NH4(+) release fitted this model when Cd2+ concentrations were 1, 5, 10 mg x L(-1). The gradual decrease of pH during adsorption of Cd2+ by Alfalfa was observed. As the competition ion of Cd2+, H+ might affect the capacity of Alfalfa root system to absorb Cd2+. The ternary linear equation results demonstrated that the content of Cd2+ absorption by Alfalfa strongly related with the release of Ca2+, Mg2+, Na+. And this exchange mainly occurred among Cd2+ and divalent cations. PMID- 22295634 TI - [Study of the removal of Pb2+ from aqueous solution by poly-gamma-glutamic acid coated magnetic nanoparticles]. AB - In this study, a novel low cost magnetic adsorbent material prepared by poly gamma-glutamic acid (gamma-PGA) coating Fe3o4 magnetic particles, which was called coated magnetic namoparticles (PG-M) was developed for the removal of Pb2+ from water by Dr. Yasuzawa. The particle size of PG-M was about 120-320 nm, and there was no significant difference in Fe3O4 and PG-M particle size, Fe3O4 was only as the support of PG-M core and did not directly involve in the reaction. The shape of PG-M was irregular cubic structure. The experiments were applied to quantify adsorptive time, pH, competitive ion and organics on the removal effect of Pb2+. The results showed that PG-M was effective in removal of Pb2+; the equilibrium amount of adsorptive was as high as 93.3 mg/g and the optimized condition of pH value for metal ions removal was 7.0, while contact time was about 45 min. The removal efficiency of Pb2+ was not significantly influenced by Na+ while was reduced with the increasing concentration of Ca2+. The removal of Pb2+ was enhanced with the presence of organic matter (humic acid, HA) when the concentration of HA was below 5 mg/L, and decreased when the concentration of HA exceeded 5 mg/L. Langmuir isotherms fitted the experimental data better compared to Freundlich isotherms. Pseudo second order model well described the sorption kinetics of Pb2+. The used PG-M can be desorbed by 0.1 mol/L HCl and became reusable. PG-M is nontoxic and eco-friendly, which have a good prospect in water treatment. PMID- 22295635 TI - [Effect of humic acids on migration and transformation of NH4(+) -N in saturated aquifer]. AB - Isothermal adsorption experiment was used to study the adsorbing process of NH4(+) -N in quartz sands under the conditions with and without humic acid; the Langmuir and Freundlich equations were used to fit the absorption result and the maximum adsorption capacity of NH4(+) -N by quarts sands was calculated. Through the soil column experiments, the concentration of NH4(+) -N, NO3(-) -N and NO2(-) -N in effluent water in the tested soil column was investigated, and the effect of humic acid on migration and transformation of NH4(+) -N in saturated aquifer was analyzed, and Pseudo-second-order Kinetics Equation and Two-step Adsorption Kinetics Rate Equation were applied to fit the kinetic processes. The results showed that both Langmuir and Freundlich models can well describe the isothermal adsorption process of NH4(+) -N on the surface of quartz sands, which means that NH4(+) -N adsorbed by the quartz sand was mainly in the form of monolayer adsorption. The humic acid could increase the adsorption capacity of NH4(+) -N on quartz sand, and the saturated adsorption capacity was 0.354 mg x g(-1) under the condition with humic acid and 0.205 mg x g(-1) with the absence of humic acid. The experiment indicated that humic acid increased the adsorption capacity of NH4(+) -N on the surface of quartz sand by increasing adsorption space in the initial stage. After saturation, humic acid influenced the migration and transformation of NH4(+) -N to NO3(-) -N and NO2(-) -N probably through providing carbon source and energy for microorganisms such as nitrifying bacteria and then resulting in lower NH4(+) -N concentration in effluent water. Both Pseudo-second order Kinetics Equation and Two-step Adsorption Kinetics Rate Equations can well describe the process of NH4(+) -N adsorption kinetics on quartz sand (R2 = 0.997 7 and R2 = 0.998 1 with humic acid; R2 = 0.992 3 and R2 = 0.994 4 without humic acid), indicating that this process was chemical adsorption. By comparing the adsorption rate coefficient of Two-step Adsorption Kinetics Rate Equation k3 (0.247 and 0.143, respectively) and k4 (0.006 27 and 0.001 7) between the treatments with and without humic acid, it can be referred that NH4(+) -N was non orientated adsorption on active points of the quartz sand at the initial stage, and the humic acid could increase the equilibrium adsorption quantity(q(e)) of NH4(+) -N on quartz sands. PMID- 22295636 TI - [Kinetic study on the photo-catalytic degradation of reactive brilliant X-3B by UVC and UVA]. AB - Different wavelengths of UV light source were studied for the degradation of reactive brilliant red X-3B to reveal the function of wavelengths in photo catalytic oxidation. The results showed that there were simultaneous photo oxidation and photo-catalytic oxidation reactions for reactive brilliant red X-3B under ultraviolet light irradiation (254 nm), while under ultraviolet light irradiation (365 nm), there were only photo-catalytic reactions. The degradation of X-3B followed apparent first-order kinetics under 365 nm ultraviolet light irradiation, it also could be depicted by formulation of L-H model more precisely, while under 254 nm ultraviolet light irradiation, it followed apparent second-order kinetics. Compared with the degradation half-life of 365 nm light, the degradation half-life of brilliant red X-3B in 254 nm light decreased from 37.263 min to 0.855 min, indicating that the light quantum efficiency of short wave UV was higher than that of the long-wave UV. PMID- 22295637 TI - [Research of the photoelectrocatalysis degradation of methylene blue of TiO2 nanotube array films annealed in oxygen atmospheres]. AB - Well-aligned and uniform titanium dioxide nanotube arrays were fabricated in situ on titanium substrate by electrochemical anodic oxidation. SEM images indicate that the TiO2 nanotubes are well organized into high-density uniform arrays,with diameter ranging in size from 70 to 100 nm. The XRD patterns show that the sample fabricated by anodic oxidation is amorphous without being annealed. As the 500 degrees C annealed sample crystallized in the anatase phase, which is in good photocatalytic activity. In quartz glass reactor, the photoelectrocatalytic degradation of MB in aqueous solutions as well as the effect factors and then to 0.1 mol/L NaCl as the electrolyte, under with in oxygen atmospheres annealed the applied bias is 0.5 V and has a pH = 3.25, light intensity is 1 000 microW/cm2 and the surface area of nano-tube array film conditions, will help to improve the TiO2 nanotubes array film photoelectrocatalysis degradation of MB degradation efficiency is 99.56%. The results of EIS analyses revealed that the surface reaction step was the only rate limiting step either for the photoelectrocatalytic process. The extra bias potential could decrease the values of the electron-transfer resistance and increase the separation efficiency of photogenerated electron-hole pairs. PMID- 22295638 TI - [Comparison study on phosphorus removal between single-stage oxic process and anaerobic/aerobic process]. AB - To compare the efficiency of phosphorus removal between anaerobic/aerobic process (SBR1) and single-stage oxic process (SBR2), two SBRs were conducted using acetate as the sole carbon source which is the most extensive substrate in municipal wastewater. The results obtained from three months experiment showed that the phosphorus removal efficiency and the TP removed on a unit MLSS were 91.72%, 3.23 mg x g(-1) (SBR1)and 71.70%, 2.91 mg x g(-1) (SBR2) respectively during steady operation. The further study found that a significant increase of PHA associated with an decrease of glycogen in SBR1 while a significant synthesis of PHA increased with the accumulation of glycogen in SBR2, indicating glycogen was not essential for the synthesis of PHA in single-stage oxic process. Furthermore, obvious phosphorus release was observed in both SBRs during idle period, but the content of phosphorus released in SBR2 (13.28 mg x L(-1)) was significantly higher than that in SBR1 (2.6 mg x L(-1)). The possible reason for SBR1 and SBR2 exhibited different phosphorus removal efficiencies was that microorganisms in both SBRs had different cyclic storage and consumption process of energy storages during metabolic process. PMID- 22295639 TI - [Effect of injected leachate C/N ratio on the denitrification of a bioreactor filled with landfilled refuse]. AB - The denitrification capacity of a landfill bioreactor was investigated under different ratios of injected leachate C/N; the denitrifying bacteria community compositions over four injection times were also studied using molecular approaches and functional gene nirS served as marker. Results showed that COD/NO3(-) -N ratio of the injected landfill leachate had a significant impact on the denitrification capacity of the bioreactor. Nitrate reduction rate increased from 1.14 mg x (kg x h)(-1) to 11.40 mg mg x (kg x h)(-1) when the injected leachate COD/NO3(-) -N ratio raised from 3.11 to 13.08. It suggested that a stable and rapid denitrification could be obtained when bioavailable COD/NO3(-) N ratio in the injected leachate was 6.37. In the bioreactor, the main denitrifying bacteria was similar to beta-proteobacteria, and others belonged to uncultured bacteria. Thiobacillus denitrificans and Azoarcus tolulyticus known as beta-proteobacteria were the dominant species and played an important role in NO3(-) -N consumption during the leachate injection. PMID- 22295640 TI - [Relationship of evaluation indexes of sludge dewatering performance under different conditioning programs]. AB - Performances of different sludge conditioners are difficult to evaluate due to the use of various evaluation indexes. Taking several traditional sludge conditioners, e.g. PAM, FeCl3 and inorganic composite conditioners as examples and five evaluation indexes include specific resistance to filtration (SRF), capillary suction time (CST), sludge settling performance, water content of sludge cake and dewatering efficiency, were investigated respectively in order to study the correlation among those indexes. The results indicate a significant positive linear correlation between SRF and CST (R2 values are 0.96 and 0.93, respectively) after adding different types of conditioners or different amount of conditioners. While they can precisely reflect plate and frame filter press efficiency, but they fail to predict the effects of centrifugal dewatering. Sludge settling performance presents the similar tendencies with SRF and CST. Since there is only limited correlation rather than strict correspondence between water content of sludge cake and dewatering efficiency. Thus, both factors should be considered synthetically in optimizing dosage performances. PMID- 22295641 TI - [Influence of bioleaching on dewaterability of cattle biogas slurry]. AB - The dewaterability of cattle biogas slurry facilitated by bioleaching was investigated through batch experiments with co-inoculation of different Acidophilic thiobacilli (Acidithiobacillus thiooxidans TS6 or Acidithiobacillus ferrooxidans LX5). The experiment was set the following 5 treatments: (1) original biogas slurry (CK), (2) 4 g x L(-1) Fe(2+) (uninoculation), (3)2 g x L( 1) S(0) + 25 mL A. t, (4) 4 g x L(-1) Fe(2+) + 25 mL A. f and (5) 2 g x L(-1) S(0) + 4 g x L(-1) Fe(2+) + 12.5 mL A. t + 12.5 mL A. f. During bioleaching, dynamic changes of pH, ORP, Fe(2+), F(3+), total Fe, the settleability, the turbidity of the supernatant after settling for 12 h, and the dewaterability (expressed as specific resistance to filtration gamma or capillary suction time, CST) of biogas slurry were monitored. Results show that specific resistance gamma and CST of bioleached biogas slurry are reduced drastically for the treatments of original biogas slurry spiked with only Fe(2+), the treatment of original biogas slurry co-spiked with Fe(2+) and Acidithiobacillus ferrooxidans LX5, and the treatment of original biogas slurry co-spiked with Fe(2+), S(0) and two Acidophilic thiobacilli. Taking the dewaterability, settleability, the turbidity of the supernatant fluid after settle 12 h and economical cost into account, the treatment of original biogas slurry co-spiked with Fe(2+) and Acidithiobacillus ferrooxidans LX5 is the most suitable pattern for cattle biogas slurry bioleaching. After bioleaching, 1.14% of organic matter, 0.09% of N, 0.05% of P, and 0.1% of K are lost in the bioleaching process, but it don't affect its fertilizer efficiency. Meanwhile, the 63.2% of Cu and 91.3% of Zn are removed from the biogas slurry, and elimination efficiencies of total coliforms in bioleached slurry exceed 99%. This study might provide a new approach for treatment and disposal of biogas slurry. PMID- 22295642 TI - [Aerobic granular sludge for simultaneous COD and nitrogen removal at high carbon and nitrogen loading rates]. AB - In a 4 L reactor, aerobic granular sludge was cultured with piggery wastewater with glucose and ammonium sulfate as the additional carbon and nitrogen sources, respectively. No exotic activated sludge was inoculated, and activated carbon powder was used to immobilize the indigenous microorganisms of wastewater in the set-up period. The reaction was conducted under controlled conditions of progressively increasing COD and NH4(+)-N loading rates, decreasing settlement time, and enhancing aeration. The resulted aerobic granular sludge was capable of simultaneous COD and nitrogen removal. The performance (COD and NH4(+)-N removal efficiencies) and characteristics of aerobic granules at high loading rates were investigated. The mature aerobic granular sludge was brown-yellow, and took an irregular spherical shape with a diameter of 0.5-3.5 mm. Under the COD loading rates of 4.80-12.6 kg x (m3 x d)(-1) and NH4(+)-N loading rates of 0.217-0.503 kg x (m3 x d)(-1), the removal efficiencies of COD and NH:4(+)-N were greater than 94% and 98%, respectively. When the COD and NH4(+)-N loading rates reached 15.7 kg x (m3 x d)(-1) and 0.723 kg x (m3 x d) (-1), respectively, the floc sludge grew quickly, and the granules disaggregated. The removal efficiency of NH4(+)-N decreased to 81.6% in four days. Yet the removal efficiency of NH4(+)-N returned to higher than 98% when the sludge was partially removed and the loading rates were reduced. The aerobic granules cultured in this study exhibited excellent abilities of simultaneous COD and nitrogen removal, and resistance to simultaneous shock of high COD and NH4(+)-N loading rates. PMID- 22295643 TI - [Methodological study on calibrating and validating model parameters of MUCT processes at low C/N ratio]. AB - Basing on ASM2d, established a mathematical model to describe the transformation of COD, TN, NH4(+)-N and TP. In terms of comparison between simulation and observed values, the kinetics and stoichiometric parameters were established in MUCT process treating a wastewater with low C/N ratio. The results showed that, the q(PHA), K(A), K(pp), Y(PO4(3-), micro(AUT) and eta(NO3(-) were 2.90 g x (g x d)(-1), 3.85 g x m(-3), 1.35 g x (g x d)(-1), 0.35, 1.6 and 0.8, respectively. The typical parameters given by the ASM2d were used as others kinetic and stoichiometric parameters. PMID- 22295644 TI - [Antibiotic resistance of bacteria to 6 antibiotics in secondary effluents of municipal wastewater treatment plants]. AB - Prevalence of antibiotic-resistant bacteria in wastewater effluents is concerned as an emerging contaminant. To estimate antibiotic resistance in secondary effluents of municipal wastewater treatment plants, antibiotic tolerance of heterotrophic bacteria, proportion of antibiotic-resistant bacteria and hemi inhibitory concentrations of six antibiotics (penicillin, ampicillin, cefalexin, chloramphenicol, tetracycline and rifampicin) were determined at two wastewater treatment plants (WWTPs) in Beijing. The results showed that proportions of ampicillin-resistant bacteria in WWTP-G and chloramphenicol-resistant bacteria in WWTP-Q were highest to 59% and 44%, respectively. The concentrations of ampicillin-resistant bacteria in the effluents of WWTP-G and WWTP-Q were as high as 4.0 x 10(3) CFU x mL(-1) and 3.5 x 10(4) CFU x mL(-1), respectively; the concentrations of chloramphenicol-resistant bacteria were 4.9 x 10(2) CFU x mL( 1) and 4.6 x 10(4) CFU x mL(-1), respectively. The data also indicated that the hemi-inhibitory concentrations of heterotrophic bacteria to 6 antibiotics were much higher than common concentrations of antibiotics in sewages, which suggested that antibiotic-resistant bacteria could exist over a long period in the effluents with low concentrations of antibiotics. Antibiotic-resistant bacteria could be a potential microbial risk during sewage effluent reuse or emission into environmental waters. PMID- 22295645 TI - [Effect of TS loading rates of biogas residue of Spartina alterniflora for secondary anaerobic digestion]. AB - Biogas residue of Spartina alterniflora treated by NaOH solution for 48h at room temperature was used for secondary anaerobic digestion with TS loading rates were 8%, 10%, 12% at (35 +/- 1) degrees C. The biogas yield, pH, and volatile fatty acid (VFA) were analyzed during the anaerobic digestion. The peak of daily gas production were 10, 14, 13 mL x g(-1) and the rates of cumulate gas production were 217, 227, 228 mL x g(-1) respectively. The methane content exceeded 65% and the lowest pH value was 7.04 during the process. The concentrations of acetic acid concentrations were 3 364, 3 286, 5 728 mg x L(-1) respectively while propionic acid and butyric acid concentrations were below 1 100 mg x L(-1). Biogas residue as a non-degradation organic compound with high potential biogas yield was decomposed slowly and no acid accumulation was not observed. PMID- 22295646 TI - [Mn content in soil of Sanjiang Plain under different land use]. AB - Mn content and its profile distribution characteristics were investigated in soils from the typical Deyeuxia angustifolia wetland, corn filed, paddy field, poplar forest and island forest in Sanjiang Plain. Results indicated that Mn content was relatively low and was in the range of 107.73-2 798.99 mg/kg with the average value of 403.24 mg/kg. Mn content significantly differed by land use (F = 9.272, P < 0.001) and was in the order of island forest > poplar forest > corn field > Deyeuxia angustifolia wetland > paddy field. On the whole, Mn content in each soil layer was in the order of corn filed > Deyeuxia angustifolia wetland > rice paddy in field and was in the order of island forest > poplar forest in the vertical direction. It suggested that Mn was enriched after wetlands were reclaimed in to the upland filed and Mn concentration was decreased when wetlands were changed into rice paddy. Correlation analysis showed that Mn content in soil significantly negatively related to pH (r = -0.279, P < 0.05), significantly positively related to sulfur (r = 0.383, P < 0.01) and dissolved organic carbon (r = 0.244, P < 0.05), and weakly related to soil organic matter and available sulfur, respectively. Changes of environmental factors had impacts on Mn species and then resulted in soil Mn content. PMID- 22295647 TI - [Effect of different soil types on the remediation of copper-pyrene compound contaminated soils by EK-oxidation process]. AB - The effect of different soil types (red soil,yellow-brown soil and black soil) on the electrokinetic (EK)-oxidation remediation of heavy metals-organic pollutant contaminated soil was studied in laboratory-scale experiments. Copper and pyrene were chosen as model pollutant, and 12% H2O2, 10% hydroxypropyl-beta-cyclodextrin and 0.01 mol x L(-1) NaNO3 solution were added into the anode and cathode cell. The applied voltage was 1 V x cm(-1). After 15 days of EK remediation, the removal rate of pyrene and copper in red soil, yellow-brown soil and black soil were 38.5%, 46.8%, 51.3% for pyrene and 85.0%, 22.6%, 24.1% for Cu, respectively. The high pH of black soil produced high electroosmotic flow and increased the exposure of oxidants and pollutants, meanwhile the low clay content was also conducive to the desorption of pyrene. The low pH and organic matter of red soil affected the chemical species distribution of Cu and increased its removal rate. It is concluded that soil pH, clay content and heavy metal speciation in soil are the dominant factors affecting the migration and removal efficiency of pollutants. PMID- 22295648 TI - [Effects of mixed chelators on the leaching of cadmium in contaminated soils under intercropping system]. AB - In order to elucidate the influence of chelators on Cd leaching in contaminated soil, outdoor soil column (100 cm) leaching experiments were conducted using two paddy soils irrigated with Pb-Zn mining wastewater. Soil samples which under intercropping systems were collected from Qingyuan City (acid soil with pH 4.63) and Lechang city (neutral soil with pH 6.51), Guangdong Province of China. The mixture of chelators (MC) comprised of citric acid, monosodium glutamate waste liquid, EDTA and KCl with molar ratio of 10 : 1 : 2 : 3 at the concentration of 5 mmol x kg(-1) soil. The intercropping system used in this study was a Zn- and Cd hyperaccumulator (Sedum alfredii) and a low-accumulating crop (Zea mays). Results showed that at day 2 after the application of MC, the Cd concentrations in leachates from every layer of neutral and acid soils increased significantly in the treatment with intercropping and MC. At day 8 the concentrations of Cd in leachate from layers below 20 cm in the neutral soil and below 60 cm in the acid soil were still significantly higher than those of control. However, the mobility of Cd was decreased greatly compared with that at day 2. At day 2 and day 8 the Cd concentrations in leachates from every layer of neutral and acid soils in the Co-crop + MC treatments exceed the value of the Groundwater Quality Standards (GB/T 14848-93). Cd in all soil columns showed the trend to migrate downwards, especially in the acid soil. The total Cd in the soil layers of 20 cm and 40 cm was decreased by 40% -58% and 39%-49% respectively at the end of the experiments compared to the initial value. After leaching of 100 days,the total Cd in 0-40 cm soil layer of acid soil reached the limit of National Soil Environmental Quality Standards (GB 15618-1995). The results also implied that in Cd-contaminated soil MC addition might enhance the potential risks of Cd contamination in groundwater. PMID- 22295649 TI - [Isolation of heterotrophic nitrifiers which can tolerate high concentration of ammonia-nitrogen and the optimization of their nitrogen removal efficiency in wastewater]. AB - The removal capabilities and tolerance of high concentration of ammonia-nitrogen of heterotrophic nitrifiers were studied. Methods included multi-point sampling, domestication, gradient dilution of domestication liquid, color indicator as rapid nitrification detection and isolation from streaking plate were conducted to screen heterotrophic nitrifiers. The strains were identified according to the sequence analysis of 16S rDNA. After inoculating the strains into ammonia nitrogen wastewater, changes of nitrogen compounds were measured in order to understand their denitrification characteristics. The denitrification efficiency was optimized by improving the C/N ratio, changing the compatibility of the strains and mixing the compatible strains with the domesticated bacterial suspension. Finally 8 high-efficiency heterotrohic nitrifiers were obtained, and named as N1-N8 respectively. Phylogenetic analysis showed that 8 strains belonged to Comamonas genus, Rhodococcus genus, Pseudomonos genus, Arthrobacter genus and Paracoccus genus, respectively. When the initial concentration of ammonia nitrogen was 256.9 mg x L(-1) and the C/N was 5.5 of the artificial wastewater, the removal rates of ammonia nitrogen by the strains were about 65%-80%, and the stain N4 was the best. When the C/N ratio of the wastewater increased to 8.0, the ammonia nitrogen removal rates of the strains correspondingly increased to about 80% -90%. As the strains compatibility, the denitrification rate of N4 + N5 + N6 was 88.2% in the artificial wastewater with initial ammonia nitrogen concentration was 261.1 mg x L(-1) and initial C/N ratio was 5.5, which was higher than that of any single strain. The ammonia nitrogen removal rate could reach to 99.8% when N4 + N5 + N6 were combined with the domesticated bacterial suspension. In the artificial wastewater, when the initial ammonia nitrogen increased to 446.9 mg x L(-1) and the C/N ratio decreased to 3.2, the ammonia nitrogen removal rate of the mixed strains which composed of N4 + N5 + N6 and domesticated bacterial suspension was 99.9%. There was almost no nitrite and nitrate nitrogen accumulated in eventually, and the total nitrogen removal rate was 66.5%. The nitrogen which was assimilated by the strains was only 33% of the lost ammonia nitrogen. It shows that the strains which could not be isolated in the domesticated bacterial suspension had significant synergies effects on ammonia nitrogen removal of the isolating strains. PMID- 22295650 TI - [Impact of land-use type changes on soil nitrification and ammonia-oxidizing bacterial community composition]. AB - A comparative study was conducted to determine nitrification potentials and ammonia-oxidizing bacterial (AOB) community composition in 0-20 cm soil depth in adjacent native forest,natural grassland, and cropland soils on the Tibetan Plateau, by incubation experiment and by denaturing gradient gel electrophoresis (DGGE) of 16S rDNA, respectively. Cropland has the highest nitrification potential and nitrate concentration among the three land-use types (LUT), approximately 9 folds and more than 11 folds than that of the forests and grasslands, respectively. NO3(-) -N accounted for 70%-90% of inorganic N in cropland soil, while NH4(+) -N was the main form of inorganic N in forest and grassland soils. Nitrification potentials and nitrate concentrations showed no significant difference between native forest and grassland soils. The native forest showed the lowest nitrification potentials and the lowest AOB diversity and community composition among the three LUT. Conversions from natural grasslands to croplands remarkably decreased the AOB diversity and composition, but croplands remain high similarity in AOB community composition compared with grasslands. The minimal and the lowest diversity of AOB in native forests directly resulted to the lowest nitrification potentials compared to natural grasslands and croplands. From the fact of the highest nitrification potentials and nitrate concentrations in croplands indicated that there were the most substantial AOB with higher activity and priority. The results provide evidence that changes of land-use type can affect both soil nitrogen internal cycling process, the diversity, community and activity of AOB, which further affect soil environment quality and the long-term sustainability of ecosystems. PMID- 22295651 TI - [Navigating through uncertainty]. PMID- 22295652 TI - [Study of polymorphisms associated to Hirschsprung's disease]. AB - Hirschsprung's disease (HSCR) is a developmental disorder characterised by the absence of the enteric ganglia along the intestine. Is regarded as the consequence of the premature arrest of the migration of neural crest cells in the hindgut during the embryonic development to form the enteric nervous system (ENS). Is considered, therefore, a neurocristopathy. The development of surgical approaches has importantly decreased mortality and morbility of Hirschsprung's patients, which has allowed the emergence of genetic studies of patients and their families. Although the genetic cause of the disease is still unknown, the RET oncogene is the main involved. Alterations in this gene have been found in HSCR patients, so many authors suggest that certain polymorphisms (SNPs) in this gene could be responsible of genetic predisposition to have the disease. Our work has consisted in the genetic analysis of the RET gene in HSCR patients using direct sequencing and genotyping with TaqMan probes. Our results show that some alleles of the polymorphisms p.Leu769Leu (c.2307T>G, Exon 13) p.Gly691Ser (c.2071G>A, Exon 11) and p.Ser904Ser (c.2712C>G, Exon 15) are associated to the disease since there are significant differences from the healthy population. PMID- 22295653 TI - [Relation between packed red blood cell transfusion and severity of necrotizing enterocolitis in premature infants]. AB - OBJECTIVE: It has been proposed recently that red blood cell transfusions (RBCT) might increase severity in infants with necrotizing enterocolitis (NEC). We intend to study if patients who have received red blood transfusions before the onset of NEC develop more severe forms of this entity. METHODS: A retrospective study was carried out including prematures with NEC. Two groups were considered: with previous RBCT (TR) and without previous RBCT (No-TR). The main outcomes of the study were severity of NEC, according to the Bell stage (BS), surgical treatment and mortality. Patients who were treated with RBCT 48 hours prior to the onset of NEC symptoms were analysed separately afterwards. Comparison of groups was made with the Fisher test or the Chi square test for the BS, surgery, mortality and nominal variables; the U Mann-Whitney test was used for numeric variables. RESULTS: Forty-six patients were included for the investigation (28 in TR and 18 in No-TR). In the TR Group 20/28 neonates reached a BS II; 8/28 BS III; 10 were operated on and there were 7 deaths. In the No-TR group 14/18 patients were classified as EB II; 4/18 as BS III, 3 patients needed surgery and Idied. No relation was found between RBCT and BS (p = 0.39), RBCT and surgery (RR = 2.7; CI 95%: 0.64-11.97; p = 0.19), or RBCT and mortality (RR = 4.5; CI 95%: 0.6-36.6; p = 0.09). In those patients who received a RBCT 48 hours before the initial symptoms there were 3 EB II and 3 EB III; 4 infants required surgical treatment and there were 2 exitus. Comparing this subgroup and the rest of the sample there were only significant differences in the need of surgical treatment: patients who received a RBCT 48 hours before the onset of NEC were at an increased risk for surgery of 2.6 (CI 95%: 1.2-5.1; p = 0.045) but there were not different when surgical treatment and mortality were considered. CONCLUSIONS: These results do not support clearly the hypothesis that there is a relation between previous treatment with RBCT and the severity of NEC. PMID- 22295654 TI - [Necrotizing entercolitis and intestinal perforation in very low weight premature infants: which is the best surgical option?]. AB - Necrotizing enterocolitis (NEC) and isolated intestinal perforation (IP) are common diseases in very low birth weight infants (VLBW) and require surgery in 20 40% of cases. We have performed a retrospective review of VLBW infants with NEC or IP who underwent a surgical procedure between 2000 and 2010, either initial laparotomy (group 1), peritoneal drain placement and subsequent laparotomy (group 2) or peritoneal drainage (group 3). Of 487 VLBW infants admitted to our hospital in the last ten years, 80 patients had NEC or IP, out of these, 31% (n=25) were treated surgically. The study population consisted of 14 girls and 11 boys with a mean gestational age of 26+3 weeks and mean birth weight of 801.4 g (range 460 to 1490 g). Pneumoperitoneum was seen in 48% of cases (n=12). Twelve patients underwent initial laparotomy, 10 patients were treated with peritoneal drainage and subsequent laparotomy and in 3 patients a peritoneal drainage was placed. Mean time between drainage and laparotomy was 69.6 hours. Sixty-eight percent of patients had NEC and thirty-two percent were IP. Survival rate was higher in the group who underwent initial laparotomy (p = 0.001) with an overall mortality of 32% (8 deaths). Optimal surgical procedure must be decided upon clinical condition of individual patients. We consider that initial laparotomy should be the treatment option in VLBW infants with intestinal perforation due to NEC or IP. PMID- 22295655 TI - [Role of peritoneal drainage in necrotizing enterocolitis in critical infants with extremely low birth weight]. AB - INTRODUCTION: Peritoneal drainage is one of the options for treatment in necrotizing enterocolitis (NEC). Currently its role is controversial as an alternative to laparotomy in low birthweight and mortality associated with both procedures is high (35-55%). MATERIAL AND METHODS: We reviewed 30 low-weight premature (< 1000 g) with NEC treated surgically. We evaluate the hemodynamic, respiratory and metabolic status of the patients, as well as multi-organ involvement and the need for inotropic drugs. These data were analyzed previos to surgery and at 6 and 12 hours. We divided the sample into two groups: those who underwent peritoneal drainage (PD) input or laparotomy (LAP). RESULTS: In the series the average birth weight was 754 +/- 156 g and gestational age was 26.1 +/ 2.1 weeks. We carry on 10 peritoneal drainage and 20 laparotomies. The DP group before the intervention showed increased heart rate, FiO2 and acidosis (p < 0.05). The needs of dopamine were similar in both groups. Following the peritoneal drainage, we found breathing improvement (adequate ventilation and oxygenation, decreased FiO2) and hemodynamic improvement (blood pressure maintained, reduced heart rate, reduced requirements for dopamine) at 6 and 12 h. DP was not the definitive treatment in any of the patiens, and all survivors (80%) of this group required further laparotomy. 62% of them died. Overall mortality was 47% (70% DP and 35% LAP, p = 0.07). CONCLUSIONS: Peritoneal drainage allowed the stabilization of low-weight premature in critical condition. The hemodynamic and respiratory stabilization was transient and did not prevent the definitive surgical treatment, although it improved the conditions for doing so. In our series, the peritoneal drainage did not improve long-term survival, questioning its role as an alternative to surgery for NEC. PMID- 22295656 TI - [Role of laparoscopy in premature infants with suspicion of necrotizing enterocolitis]. AB - INTRODUCTION: The indication of surgery in necrotizing enterocolitis (NEC) can be difficult in the absence of pneumoperitoneum or peritonitis. We propose laparoscopy for early diagnosis of intestinal perforation or necrosis in order to avoid unneccessary laparotomies. MATERIAL AND METHODS: A new protocol was proposed which included diagnostic and therapeutic laparoscopy in cases of uncertain surgical ECN indication. Subsequently, a prospective study of the 7 patients who underwent laparoscopy was performed, analyzing pathophysiological effects in the premature, technical difficulties of the procedure, and postoperative diagnostic consistency. RESULTS: The mean gestational age at birth was 27 weeks (range 25 to 31) with an average weight of 1.147 kg (range 0.900 to 1.600) two trocars were placed as the focal oriented scanning or radiography, using a pneumoperitoneum 6-10 mmHg for an average of 17 min. Laparoscopy avoided laparotomy in a patient who did well after washing and drainage and magnified lesions in one patient who did not require laparotomy after intestinal bypass. In other cases, laparoscopy was followed by minilaparotomy oriented to the lesions and stoma formation. There were no surgical complications attributable to the procedure, which was well tolerated in all cases. CONCLUSIONS: Laparoscopy can be a useful tool for evaluation of lesions of NEC in cases of uncertain surgical indications. In our experience, it is well tolerated in neonates of low weight, allowing oriented minilaparotomies or even to avoid laparotomy. PMID- 22295657 TI - [Small left colon syndrome: a review of our experience]. AB - OBJECTIVE: The object is to present our experience with the small left colon syndrome (SLCS) and to investigate the usefulness of the anorrectal manometry in the study of these patients. MATERIAL AND METHODS: This was a retrospective review of the clinical histories of 10 patients treated in our Hospital for SLCS. The following variables are valued: sex, mother precedents, type of childbirth, gestational age, birth weight, clinical presentation (low colonic obstruction), delayed meconium passage, contrast enema with gastrografin, anorrectal manometry and treatment (Nursing, days of digestive rest, time of parenteral nutrition). RESULTS: During the study period, 10 patient were identified (5 are men). SLCS is reported in 2 sets of twins; in one set both twins are affected and in the other set 1 twin is affected. Maternal diabetes was identified in 6 patients. The mean gestational age was 36.6 + 2.11 weeks, and the weight 3001 +/- 689.72 g. 2 patient presented anomalies associated: fetopatia diabetic, hemivertebras D11-L2. All 10 infants presented abdominal distention and vomiting at 48.73 +/- 45.39 hours of life. Only 2 presented meconium passage in the first 24 hours. The contrast enema with gastrografin performed show typical findings of this syndrome in all cases. The anorrectal manometry carries out in 8 patients and demonstrates presence of the recto-anal inhibitory reflex (RAIR) in 5 and absence in 3. In these 3 patients with no RAIR, the study was repeated weekly until the presence being observed (normally between 2a and 3a week of life). In 1 newborn was necessary colostomy; the suction rectal biopsy showed immaturity of ganglionars cells and the manometric control previously at the close of the colostomy (9 months) showed presence of the RAIR. Conservative treatment (nursing and digestive rest) was successful in all cases with a mean of duration the 6.40 +/- 5.10 days. 6 patient needed parenteral nutrition during 7.30 +/- 8.49 days. The mean of discharge was 17.78 +/- 13.28 days. The clinical development was favourable in all the cases. CONCLUSIONS: The contrast enema with gastrografin is diagnostic and therapeutic and together with the nursing, has allowed solve the distal intestinal obstruction in 9 cases (90%). In the newborns with absence of RIAR, the anomanometric controls have allowed to know the moment of the maturation of the anorectal function. PMID- 22295658 TI - [Are we correctly treating pilonidal disease in children? therapeutic goals beyond preventing recurrence]. AB - INTRODUCTION: We present a retrospective study of our paediatric patients affected by pilonidal disease over the last 5 years. PATIENTS AND METHOD: In all cases a broad excision of the pilonidal tissue was made, without colour signing the different incision sites and primary closure of the defect with no drainage. RESULTS: Using this technique we treated 20 adolescents (15 girls and 5 boys) of ages between 12 and 15 years (average age 13.3 years) and body mass index between 17 and 33 (mean BMI 26.4 kg/m2). Mean hospitalisation time was 1.45 days. Preoperative antibiotherapy with Amoxicillin-clavulanic was administered to 55% of patients and continued over the first postoperative week. We had four cases with recurrence of the disease (25%) (two of these with two recurrences), which we treated with three primary closures on the midline and three by flattening the cleft. In 2 cases with dehiscence of the wound we allowed treatment by secondary intention. No flaps or marsupialisation were attempted in any case. In all cases the result was aesthetically satisfactory, with maintenance of the intergluteal fold. CONCLUSIONS: In our series we have succeeded in undertaking primary closure of the defect after pilonidal resection without any excessive tension. This treatment enables a rapid return to a normal routine. We considered it important to undertake surgery that maintained the intergluteal fold, especially in patients with a short-term evolution of the disease, reserving flattening the cleft, closure by secondary intention, or primary closure by inserting flaps only for cases of recurrent disease; those with long-term evolution; or patients with complex lesions prior to surgery. Nutritional support to reduce overweight is very important in many patients. PMID- 22295659 TI - [Evaluation of the risk of the clinical-surgical and pathology study findings in newborns with necrotizing enterocolitis who have received surgical treatment]. AB - INTRODUCTION: Despite advances in neonatal care between 20% and 63% of children with necrotizing enterocolitis (NEC) require surgery. The aim was correlation the risk factors of infants with NEC "IIB / IIIA / IIIB" Bell and the clinical, surgical and pathological findings. METHOD: In the children with diagnosis of NEC surgically treated, were analyzed of variables: clinical, surgical and pathological findings. We studied two groups: control (n=5) and NEC group (n=12). Comparisons were made between groups using the Mann-Whitney U- and the Spearman coefficient (r). To assess the risk of morbidity / mortality associated with the extent of intestinal resection we applied the Cox regression. RESULT: We found differences (p < 0.05) between control group and the NEC group regarding Bell, the mean height of villi, Chiu and the number of goblet cells. In the NEC group we find correlations (p < 0.05) from Bell, regarding Chiu (r = 0.761), resection of the colon (r = 0.687), pneumatosis / perforation (r = 1) and the mean height of villi (r = -0.878). The gut reseccion was at 26 cm (3-107). We observed a risk of 1.04 in the neonatal period (p > 0.05) of mortality or consequence post enterocolitis associated with the extent of bowel resection. CONCLUSION: The decrease in the average height of villi, the highest level of microscopic intestinal injury and reduced goblet cell population contributes to a greater extent of intestinal resection, which favors the risk of death or developing consequence post-enterocolitis. PMID- 22295660 TI - [Nonpalpable testes: laparoscopy for inguinotomy]. AB - INTRODUCTION: The nonpalpable testis refers to the inability to make objective the teste through exploratory maneuvers. These patients have benefited from the laparoscopic approach that previously they could require even a laparotomy. Definitive treatment of nonpalpable testis depends on the laparoscopic findings, being in dispute their resolution in one or two stages. The aim of this study is to assess the incidence and the results after the application of laparoscopy for the treatment of nonpalpable testis in our department. PATIENTS AND METHODS: All the cases of nonpalpable testis between 2000-2009 are selected. The age of intervention, laterality, operative findings, treatment performed and the size of the testes in cases operated in two stages are analized. RESULTS: Fifty-eight children are reviewed with a total of 60 testis. Thirty-one cases are left (53.4%), 25 are rights (43.1%) and 2 are bilateral (3.5%). In 32 children the testis is absent or atrophic, in 10 the Fowler-Stephens technique is developed, 8 gonads are next to the internal inguinal ring, 5 are in the inguinal canal and 2 is so high and so hipoplasic that orchiectomy is decided. Of those operated in 2 stages, 9 testes survive after the first time and 7 of them have a normal size 6 months after the second surgery. CONCLUSIONS: Laparoscopy is an effective method for diagnosis and treatment of non palpable testis, however, there is still no consensus, for certain locations, to descend the testicle in 1 or 2 stages and if the way is by laparoscopy or inguinotomy. PMID- 22295661 TI - [Value of the direct cystoscintigraphy in the diagnosis of vesicoureteral reflux in patients with prenatal hydronephrosis]. AB - OBJECTIVE: As the radiation received in conventional cystography is about 20 times higher than radionuclide cystography and the sensitivity of the last is higher in order to diagnose vesicoureteral reflux, we consider the use of radionuclide cystography in early detection of reflux in patients with prenatally detected hydronephrosis. MATERIALS AND METHODS: Between 2003 and 2009, a study of neonates with prenatal history of hydronephrosis was performed in order to rule out reflux. Our protocol was as follows: The diagnosis was confirmed by postnatal ultrasound at 1 week (in this case patient initiate antibiotic prophylaxis). A new ultrasound was repeated at 6 weeks, if the dilatation was larger than 8 mm at this time, direct radionuclide scintigraphy was performed. The patients were placed on prophylactic antibiotics until the screenining results were known. Conventional cystography was performed if a male infant showed severe dilatation, or in general in cases with parenchymatous atrophy or if a duplex system was suspected. RESULTS: In 13 (20%) of the 65 cases (18 kidneys) reflux was detected (3 minor, 8 moderate and 7 severe). In most cases, follow up was performed with radionuclide cystography. None of the patients with reflux placed on prophylactic antibiotics developed a febrile urinary tract infection during the first year of life. CONCLUSIONS: Direct radionuclide cystography is a useful diagnostic method in early detection of vesicoureteral reflux in patients with prenatal hydronephrosis with higher sensitivity than conventional cystography, and with an important advantage concerning radiation of the patient. Patients screened and placed on prophylactic antibiotics are probably going to present less episodes of pielonephrytis. PMID- 22295662 TI - [Stephens-Fowler in two times: results 14 years later]. AB - The management of intra-abdominal testis can be challenging, as evidenced by the multiple methods suggested for its assessment and treatment. In this paper, we report our long-term results for our 14-year surgical experience with laparoscopic management. Methods. Retrospective study of laparoscopic interventions performed at our department for nonpalpable testes between 1996 and 2009. In 174 procedures, we found 72 intra-abdominal testes (5 bilateral) and 25 direct orchiopexies (3 bilateral) were performed. One-stage Fowler-Stephens orchiopexies (FSO) were performed in 5 children. 40 boys underwent the two-stage FSO technique (2 bilateral) in those that reached the contralateral inguinal ring. The second stage was performed in 4 cases with a laparoscopic approach, the rest of them underwent an inguinal procedure exclusively. Mean age for the first intervention was 3.7 yrs, and the second stage was performed on average after 10.9 months. Of 42 undescended testes, 22 were on the right side and 20 on the left side. Median followup was 24 months. Results. Of 42 two-stage FSOs performed, 27 surgeries were very successful, with a testis size equivalent to the contralateral mate; 7 had good results, with a smaller testis (volume up to 50% of contralateral); and 7 resulted in atrophic testis. No complications were encountered during surgery. Conclusions. There is no doubt about the usefulness of laparoscopy for intra-abdominal testes with short spermatic vessels, and the two-stage Fowler-Stephens technique should be the procedure of choice given its high success rate. PMID- 22295663 TI - [Perinatal neonatal lesions: retrovaginal tears]. AB - Neonatal injuries produced during the childbirth or in the maneuvers of resuscitation they have a high morbidity and suppose the 8th reason of mortality in newborns. The aim of this article is to check our casuistry in the last 10 years and to present a case report of rectovaginal tear with the possible therapeutic options published in the literature. There were gathered a total of 8 perinatal neonatal injuries, being the majority of them clause-contused (5) in hairy leather, pinna and thorax. Other cases were affecting the perine: an anal tear and two rectovaginal tears; one of these patients needed colostomy and surgical repair of the perine. Only a small percentage of the perinatal neonatal injuries are valued by the paediatric surgeon. Some of them are serious and can have important consequences. The colostomy and primary or secondary closing is a therapeutic sure option in rectovaginal tears. PMID- 22295664 TI - [Congenital solitary infantile myofibroma: report of two cases]. AB - The infantile myofibromatosis is a rare pathology usually affecting children under 2 years. More than half are congenital, located in head and neck in a 30% of the cases. Myofibroma is a benign mesenchymal tumor that appear an isolated lesion or multiple, with or without visceral involvement. Case 1: A newborn girl that presents lump in scalp suspected of encefalocele. Ultrasound and RM: solid and heterogeneous mass 4 x 2 cm with increased peripheral vascularisation. Case 2: A 7-month-old baby boy with lump in right occipital zone detected at 4 months. Ultrasound and RM: injury 1 x 1.5 cm in head esplenio muscle suggestive of hemangioma. RESULTS: After surgical total resection, the histological study and immunohistochemical identified the lesion as myofibroma. The evaluation of disease dissemination was normal and the recovery of the patients was favorable. The differential diagnosis of myofibroma must be carried out with other mesenchymal tumors and with non neoplastic injuries characteristics of the region affects. The visceral location and multiple forms worsen the prognosis, so is important do an exhaustive study. Treatment is conservative surgery, but if there is no risk to the child, the possibility of spontaneous regression makes the abstention therapeutic a correct alternative. PMID- 22295665 TI - Unschooled in hard knocks. PMID- 22295666 TI - Science and prejudice. PMID- 22295667 TI - Tensions over taikonauts. PMID- 22295668 TI - A man-made contagion. PMID- 22295669 TI - Just a click away. PMID- 22295670 TI - Peeling away microbes. PMID- 22295671 TI - Gumming up appetite. PMID- 22295672 TI - Making liquids go bipolar. PMID- 22295673 TI - A diabetes cliffhanger. PMID- 22295674 TI - The future is for fools. PMID- 22295675 TI - Is space digital? PMID- 22295676 TI - The great prostate cancer debate. PMID- 22295677 TI - Swept from Africa to the Amazon. PMID- 22295678 TI - Sleeping with the enemy. PMID- 22295679 TI - All hands on deck. PMID- 22295680 TI - The future of chocolate. PMID- 22295681 TI - The collision syndrome. PMID- 22295682 TI - Fetal armor. PMID- 22295683 TI - The brittle star's apprentice. Interview by Gareth Cook. PMID- 22295684 TI - Lies we tell ourselves. PMID- 22295685 TI - How science degrees stack up. PMID- 22295686 TI - [Study of sharing platform of web-based enhanced extracorporeal counterpulsation hemodynamic waveform data]. AB - Enhanced extracorporeal counterpulsation (EECP) information consists of both text and hemodynamic waveform data. At present EECP text information has been successfully managed through Web browser, while the management and sharing of hemodynamic waveform data through Internet has not been solved yet. In order to manage EECP information completely, based on the in-depth analysis of EECP hemodynamic waveform file of digital imaging and communications in medicine (DICOM) format and its disadvantages in Internet sharing, we proposed the use of the extensible markup language (XML), which is currently the Internet popular data exchange standard, as the storage specification for the sharing of EECP waveform data. Then we designed a web-based sharing system of EECP hemodynamic waveform data via ASP. NET 2.0 platform. Meanwhile, we specifically introduced the four main system function modules and their implement methods, including DICOM to XML conversion module, EECP waveform data management module, retrieval and display of EECP waveform module and the security mechanism of the system. PMID- 22295687 TI - [Research on magnetoencephalography-brain computer interface based on the PCA and LDA data reduction]. AB - The magnetoencephalography (MEG) can be used as a control signal for brain computer interface (BCI). The BCI also includes the pattern information of the direction of hand movement. In the MEG signal classification, the feature extraction based on signal processing and linear classification is usually used. But the recognition rate has been difficult to improve. In the present paper, a principal component analysis (PCA) and linear discriminant analysis (LDA) method has been proposed for the feature extraction, and the non-linear nearest neighbor classification is introduced for the classifier. The confusion matrix is analyzed based on the results. The experimental results show that the PCA + LDA method is effective in the analysis of multi-channel MEG signals, improves the recognition rate to the extent of the average recognition rate 55.7%, which is better than the recognition rate 46.9% in the BCI competition IV. PMID- 22295688 TI - [Design and implementation of pupil auto-tracking system in the perimeter]. AB - The pupil auto-tracking system is a key component of the full-automatic perimeter. Taking the advantage of integral image in counting characteristic value rapidly, we studied the relationship between training stages and total error detection rate based on the training of Adaboost strong classifier. Besides, a testing strategy of amplification detection window was introduced, and a multi-stage cascaded eye classifier for eye detection was proposed finally. It kept the same detection rate as the commonly trained strong classifier with a much lower error detection rate. In the meantime, the present article explaines the main arithmetic implement functions, as well as designs the motion control program for the jaw bracket system. PMID- 22295689 TI - [Development of a lung cancer image database and visualization toolkit]. AB - Lung cancer is the most common tumor and one of the malignant tumors with the lowest livability after diagnosis, as is known so far. Large-scale image database is the foundation of developing computer-aided diagnosis methods, education and training in lung cancer diagnosis to improve medical diagnostic efficiency and to reduce the doctors' burden. In this study, aiming at improving the low data storage efficiency and solving the lacking of tool for data visualization and data retrieval existing in the use of traditional Lung Image Database Consortium (LIDC) from the lung cancer database, we developed a new lung cancer image database platform including an improved data model, a data integration tool, an image and annotation visualization tool and a data retrieving component. Firstly, the data format in LIDC was analyzed and an improved information model was provided to manage and manipulate large amount data stored in it. Next, some tools such as data integration component, DICOM, image and annotation visualization tool, and data query were designed and implemented. The study demonstrated that the lung cancer image database platform had the capacity of data collection, visualization, and query, and could promote diagnose lung cancer research. PMID- 22295690 TI - [Time effect of sinusoidal electromagnetic field on enhancing the maturation and mineralization of osteoblasts in vitro]. AB - The present research was to investigate the time effect of sinusoidal electromagnetic fields (SEMFs) at different exposure time on the proliferation and differentiation of osteoblasts (OB) in vitro. The newborn rat calvarial OB were isolated by enzyme digestion and divided randomly into 7 groups after one passage. The exposure times of the SEMFs were 0.5 h, 1.0 h, 1.5 h, 2.0 h, 2.5 h and 3.0 h, respectively, and the frequency was 50 Hz. The cells were exposed in the SEMFs of 1.8 mT. Those without SEMFs exposure were used as the control group. They were observed under the contrast phase microscope each day. After 48 h, cell proliferation was assayed by MTT method. The alkaline phosphatase (Alkaline Phosphatase, ALP) activities were measured after the exposure of SEMFs for 3 d, 6 d, 9 d and 12 d, respectively. The calcified nodules were stained by Alizarin Bordeaux after 10 d. The cells exposed in the SEMFs were arranged in Spiral appearance after 8 d. The SEMFs exposure time at 2.0 h, 2.5 h and 3.0 h significantly inhibited cell proliferation (P < 0.01) and 0.5 h, 1.0 h, 1.5 h groups more significantly than control groups (P < 0.05). When the 3 d, 6 d and 12 d the ALP activities of the 0.5 h, 1.0 h, 1.5 h and 2.0 h, times group were significantly higher than those in the control group (P < 0.05), and after 9 d the 1.0 h, 1.5 h and 2.0 h activity of ALP higher significantly than control and other groups (P < 0.01). Other groups had no effect on the ALP activity. Alizarin Bordeaux staining result showed the amounts of calcified nodules 1.0 h, 1.5 h and 2.0 h higher than control groups. The SEMFs at 50 Hz, 1.8 mT different time exposure groups inhibits the proliferation of OB, but they enhances the maturation and mineralization of the OB and SEMFs at 1.8 mT of the 1.5 h has the strongest activity. PMID- 22295691 TI - [Effectively extraction of flash visual evoked potential based upon wavelet transform and detection of non-invasive intracranial pressure]. AB - The signal of flash visual evoked potential (FVEP) is very weak, and often submerges into strong noise environment, like spontaneous electroencephalogram (EEG) signal, so effective de-noising methods should be taken to extract FVEP waveform exactly. In this paper, based upon the frequency feature of FVEP, we use average technology and multi-resolution wavelet transform to filter spontaneous EEG signals, and FVEP can be extracted effectively as a result. While the potential latency corresponding to the N2 wave in the FVEP waveform picked-up is related to intracranial pressure (ICP), the Non-invasive detection of ICP can be realized. PMID- 22295692 TI - [An adaptive ultrasound sound speed optimization based on image contrast analysis]. AB - In order to get real time ultrasound images with clear structure and improved contrast, an adaptive ultrasound sound speed optimization method based on image contrast analysis was investigated. It firstly introduced the dynamic beamforming of ultrasound system, as well as the definition of assumed system's sound speed and the true sound speed propagated in tissues the degrade image quality due to their mismatch was also discussed. After given the pixel gray level value based ultrasound image contrast ratio, the basic idea to precisely estimate the true sound speed for real time system sound speed was proposed. Algorithms have been verified both in tissue-mimicking phantoms with known sound speeds and in vivo ultrasound images, compared with other existing method. The testing results showed that this new method not only produced accurate sound speed for ultrasound image optimization, but also finely met the critical computation requirement for real time applications. PMID- 22295693 TI - [Empirical mode of combination of the wavelet threshold filtering and empirical mode decomposition (EMD) based on energy estimate]. AB - According to the frequency overlapping of intrinsic mode function (IMF) based on the temporal and spatial filtering of empirical mode decomposition (EMD), which will lead to the question of useful signals and noises filtered together, we proposed a method that numbers of IMF is determined by energy estimate, temporal and spatial filtering combing wavelet threshold and EMD integrating wavelet local signal characteristics of time and scale domain. This method not only used multi resolution wavelet transform features, but also combined the EMD and Hilbert decomposition of the adaptive spectral analysis of instantaneous frequency and significance of the relationship between energy, so as to solve the problem of useful signal being weakened. With MIT/BIH ECG database standard data subjects, experimental results showed it was an effective method of data processing for handling this type of physiological signals under strong noise. PMID- 22295694 TI - Usefulness of quantitative proton MR spectroscopy in the differentiation of benign and malignant meningioma. AB - This study was aimed to explore the value of quantitative proton MR spectroscopy (1H-MRS) in the differentiation of benign and malignant meningioma. 23 cases, including 19 benign (grade I) and 4 malignant (grade II-III) meningiomas, underwent single voxel 1H-MRS (TR/TE = 2000 ms/68, 136, 272 ms). T2 relaxation time of tissue water and choline were estimated by an exponential decay model. Choline concentration was calculated using tissue water as the internal reference, and corrected according to intra-voxel cystic/necrotic parts. Tissue water T2 of benign and malignant meningiomas were (105 +/- 41) ms and (151 +/- 42) ms, respectively. The difference was statistically significant (P = 0.033). While Choline T2 of benign and malignant meningiomas were (242 +/- 73) ms and (316 +/- 102) ms respectively, the difference was not significant (P = 0.105). Choline concentration was (2.86 +/- 0.86) mmol/ kg wet weight in benign meningiomas and (3.53 +/- 0.60) mmol/kg wet weight in malignant ones; after correction they increased to (2.98 +/- 0.93)mmol/kg wet weight and (4.58 +/- 1.22) mmol/kg wet weight, respectively, and the difference was significant (P = 0.019). In conclusion, quantitative 1H-MRS is useful for the differentiation of benign and malignant meningioma by T2 relaxation time and absolute choline concentration. PMID- 22295695 TI - [ANSYS simulation of subcutaneous pustule electrical characteristics]. AB - With the growing number of clinical surgery, post-operative surgical wound infection has become a very difficult clinical problem. In the treatments of it, non-invasive test of wound infection and healing status has a significance in clinical medicine practice. In this paper, beginning with the electrical properties of skin tissue structure and on the basis of the electromagnetism and the human anatomy, using the finite element analysis software, we applied safe voltage on the 3D skin model, performed the subcutaneous pustule simulation study and gained the relational curve between depth and radius of the pustule model. The simulation results suggested that the method we put forward could be feasible, and it could provide basis for non-invasive detection of wound healing and wound infection status. PMID- 22295696 TI - [Study on computer-aided diagnosis system based on multidetection]. AB - This paper, analyzes the defects and its limitations of computer-aided diagnosis system (CADS) in clinical practice in the past, proposes a new pattern CADS of designing method. We used the theory of multidetection, stored the accumulated experience in computer, established the knowledge base, and made the medical diagnosis through maximizing a posteriori (MAP) judgement rule. Statistical data revealed that the CADS had a high accuracy rate. The medical diagnosis can meet the demand for clinical treatments, and realize the clinical diagnostic application of information technology. PMID- 22295697 TI - [The estimation of higher order aberrations in children with anisometropic amblyopic]. AB - Higher order aberrations (HOAs) were measured in 54 anisometropic amblyopic children using the ZY-WAVE II aberrometer. The results were compared in normal fellow and amblyoic eyes which were determined by the corrected visual acuity. Between the normal eyes and anisometropic amblyopic eyes, no statistically significant difference were found in mean root square of total HOAs, total coma (TC), total spherical aberration (TSA), and the 5th root mean square (RMS5). There was no correlation among best corrected visual acuity (BCVA), HOAs, TC, TSA, and RMS5. There was some positively correlation between the degree of anisometropia and TC. HOAs increase with the increasing of the degree of anisometropic amblyopia. Lower order aberrations are the main refractive factors leading to amblyopia, and HOAs is related to anisometropia amblyopia. The study helps us understand the mechanism of amblyopia and make the further study. PMID- 22295698 TI - [Development of an implantable animal activity rhythm detector and the low-power design]. AB - This paper mainly introduces how to use C8051F330 MCU to design an implantable (implanted) animal activity detector with low-power technology. Through the animal activity data detected by the device, animal activity rhythm can be reflected indirectly, which provides good basis for the research of animal rhythm. Research results showed that the device, which could also provide a reliable experimental platform for further study of chronobiology (biological rhythm) in animals by detecting the signal of animal activity, has the advantages (characteristics) of good performance, lower power consumption, simple operation and highly reliability. PMID- 22295699 TI - [The study of active noise control method for noisy surgery tools]. AB - Noise problem is encountered in many types of surgery, especially in orthopaedic surgery, where the cutting tool and its actuation part such as motor always generates big noise. This work is dedicated to developing a novel and promising solution based on the active noise control (ANC) technology to solve the noise problem in an orthopaedic theatre. The development process began with building an engineering evaluation model (EEM) to analyze the specifics of sound interactions and sound field involved in the noise problem. This model can describe the acoustic problem in a straightforward way, help to design a good control system and furthermore to assess the result and to optimize the control structure. Then the "auto position tracking near head space ANC" strategy was proposed from the model study. Furthermore, the real sound field measurement experiment proved the possibility of proposed design. PMID- 22295700 TI - [The numerical simulation of the internal flow field inside the pressure generator of a continuous positive airway pressure ventilator]. AB - The problem of noise in ventilator has always been an important topic to study in the development of the ventilator. A great number of data are showing that there are still large gaps of research and application levels in noise control of the ventilator between China and some more advanced foreign countries. In this study, with cooperation of the Shanghai Medical Equipment Limited Liability Company, we used the computational fluid dynamics (CFD), software FLUENT, adopted the standard k-epsilon turbulence model and the SIMPLE algorithm to simulate the inner flow field of the continuous positive airway pressure (CPAP) ventilator's pressure generator. After a detailed analysis, we figured out that there are several deficiencies in this ventilator, like local reflow in volute, uneven velocity distribution and local negative pressure in inlet of the impeller, which easily lead to noise and affect the ventilator's performances. So, it needs to be improved to a certain extent. PMID- 22295701 TI - [The design, preparation and compressive strength testing of interbody fusion cages made from a composite of multi-amino acid copolymer/tri-calcium phosphate]. AB - This research was to design and prepare interbody fusion cages using composite materials of multi-amino acid copolymer/tri-calcium phosphate (MAACP/TCP) and to test compressive strength of the cages. 16 specimens of C3-4 segments from female adult goats were scanned by X-ray to exclude disease of cervical spine, and then anatomical data were measured, i. e. disc space height of C3-4 segment (DSH), sagittal diameter of C3 lower endplate (SDLE3), sagittal diameter of C4 upper endplate (SDUE4), coronary diameter of C3 lower endplate (CDLE3), and coronary diameter of C4 upper endplate (CDUE4). According to the anatomical data, we designed and prepared the interbody fusion cage using the composite of MAACP/TCP and titanium with the same sizes. The MAACP/TCP Cages were made with the method of injection molding and finish machining, and titanium Cages were made with machining. In the testing of compressive strength of Cages, the specimens were divided into three groups, tricortical iliac crest bone group (isolated from goats), MAACP/TCP Cage group and titanium Cage group. There were 8 specimens in every group with the same sizes, the length of 12 mm, the width of 10 mm, and the height of 6 mm. The compressive strength of all specimens was tested on a universal testing machine. The values of DSH, SDLE3, SDUE4, CDLE3 and CDUE4 were (4.78 +/- 0.17) mm, (15.06 +/- 0.53) mm, (12.46 +/- 0.44) mm, (14.47 +/- 0.51) mm and (12.15 +/- 0.65) mm, respectively. MAACP/TCP Cage was successfully designed and made with a compressive strength of 76.34 MPa, which was much higher than that of tricortical iliac crest bone (18.41 MPa). The maximal loading of universal testing machine was 50 000 N, so the compressive strength of titanium Cages, whose value should be more than 541.35 MPa, could not be tested precisely. It is feasible to make cages with MAACP/TCP composite, and the compressive strength of MAACP/TCP Cages was much higher than that of tricortical iliac crest bone isolated from goats. PMID- 22295702 TI - [Study on the haemostatic efficiency of composite bio-particles]. AB - A porous composite particle (CP) was fabricated by the methods of emulsification and cross-link based on chitosan, alginate and collagen protein, and the tranexamic acid-loaded composite particles (TACP) was prepared by immersing the composite particle into the solution of tranexamic acid and by freeze drying. In the hepatic and splenic hemorrhage model of rabbits, CP and TACP were randomly used as haemostatic agents, and the Suxiaozhixuefen (Flashclot) was used as control. The corresponding hemostatic time and bleeding amount were observed respectively. The hemostatic time of CP and Flashclot were (2.48 +/- 0.88) min and (3.07 +/- 0.84) min, respectively, no significant difference was observed. However, the hemostatic time of TACP was (1.90 +/- 0.75) min, which was significantly shorter than that of CP and Flashclot (P < 0.05). In the splenic bleeding model of rabbits, similar results were obtained with these three kinds of hemostatics. These results indicated that the CP based on chitosan, alginate and collagen protein displayed similar hemostatic efficiency to Flashclot. However, the TACP might be one of promising haemostatic powders due to its more excellent hemostatic efficiency. PMID- 22295703 TI - [Study on relationship of dose-effect and time-effect of APA microencapsulated bovine chromaffin cells on pain treatment]. AB - This study was to investigate the relationship of dose-effect and time-effect of Alginate-Polylysine-Alginate (APA) microencapsulated bovine chromaffin cells on the treatment of pain model rats. Using a rat model of painful peripheral neuropathy, the antinociceptive effects of APA microencapsulated bovine cells transplanted into the subarachnoid space was evaluated by cold allodynia test and hot hyperalgesia test. Compared with control group, the withdrawal difference with cell number 50 thousands groups, 100 thousands groups and 200 thousands groups was reduced (P < 0.05), and the difference decreased with the cells increases, indicating a significant analgesic effect. There was no significant difference between 400 thousands groups and 200 thousands groups. This analgesic effect maintained longer than 12 weeks. There was a positive correlation between the analgesic effect and the quantity of APA microencapsulated bovine chromaffin cells which were transplanted to treat pain model rats, and the effective antinociception remained longer than 12 weeks. PMID- 22295704 TI - [Adipose differentiation and adipose tissue engineering of bone marrow-derived mesenchymal stem cells using pluronic F-127 hydrogel in vitro]. AB - The aim of this study is to investigate the growth and proliferation of bone marrow mesenchymal stem cells (BMSCs) three-dimensionally cultured in Pluronic F 127 gel, in order to explore the cellular compatibility of gel and to investigate the feasibility of BMSCs differentiating into adipocytes in gel. Rat BMSCs were isolated from adult bone marrow, and then cultured and amplified in vitro. The BMSCs derived from the 4th passage were seeded on the scaffolds and incubated in adipogenic stimuli culture to differentiate into adipocytes. BMSCs were dispersed into gel and cultured in vitro for two weeks then the status of adhesion, growth and proliferation of the cells were observed. The edipogenic differentiation of the BMSCs was assessed by cellular morphology and further confirmed by Oil Red O staining. BMSCs were able to attach, grow and proliferate well in Pluronic F-127 gel. The BMSCs differentiated into adipocytes in gel in the presence of adipogenic stimuli over a period of 2 weeks. After only 4 days of adipogenic induction, small lipid droplets were observed within BMSCs in gel wells treated with differentiation media. At the end of 14 days, in the presence of differentiation media in gel, the size of the lipid droplets increased to occupy most of the cytoplasm, consistent with differentiation of BMSCs into adipocytes. Lipid droplets in differentiating BMSCs were positively stained with Oil Red O in the presence of differentiation media in the Pluronic F-127 treatment. We demostrated BMSCs incubated in the 3D Pluronic F-127 gel scaffolds could be induced and differentiated into adipocytes. The system for inducing differentiation of BMSCs into adipocytes is promising to apply in the construction of tissue engineering adipose tissue and the repair of fat injury, and Pluronic F-127 gel may be a suitable scaffold for cellular therapy of BMSCs. PMID- 22295705 TI - [Study on preparation of acellular matrix material fixed by oxidized sodium alginate and its cytocompatibility]. AB - This study was intended to investigate the crosslinking characteristics of a new crosslinking agent-oxidized sodium alginate (ADA), which might provide an ideal biological crosslinking reagent for the construction of soft tissue bioprostheses. Glutaraldehyde and genipin, which have been typically used in developing bioprostheses, were used as controls. The porcine aortas were treated by these three crosslinking agents for 15 min to 72 h and the fixation index was determined. Subsequently, the mechanical property and cytocompatibility of fixed tissues were also tested. The results indicated that fixed tissues by ADA were comparable as glutaraldehyde and superior to genipin controls in fixative efficiency. It was also found that tissues fixed by ADA were comparable as genipin and superior to glutaraldehyde controls in cytocompatibility and were similar to natural tissues in mechanical property. The results of in vitro study demonstrated that ADA could be a promising crosslinking reagent for biological tissue fixation. PMID- 22295706 TI - [Research on the extracorporeal cytocompatibility of a composite of HA, carbon fiber and polyetheretherket-one]. AB - The present research was to study the biocompatibility of a composite of hydroxyapatite (HA), carbon fiber (CF) and polyetheretherket-one (PEEK) by co culturing with the osteoblasts in vitro. Cell relative growth (RGR) was used as a quantitative assessment for cytotoxicity of the biomaterials by CCK-8. The proliferation index of the co-cultured cells and ALP activity was measured to study the effect of PEEK-HA-CF composites. Morphological properties of the osteoblast cells in vitro were observed by scanning electro-microscopy (SEM). The PEEK-HA-CF materials have no cytotoxicity to osteoblasts. The proliferation index of PEEK-HA-CF was higher than that of Ti alloy group, but these was no significant difference compared to that of control group. The ALP activity was the highest on PEEK-HA-CF composites surface after 7 days. The osteoblast cells co-cultured with the PEEK-HA-CF composite were adhered well to the biomaterial as observed under the SEM. The results suggested that the PEEK-HA-CF composites had good biocompatibility in vitro and might be a novel orthopedic implanted material. PMID- 22295707 TI - [Identification of oligopeptides binding to Mycoplasma hyorhinis P37 using a phage display library]. AB - Phage display random heptapeptide library was screened with recombinant P37 in this study. The positive phage clones were identified by ELISA and were sequenced, and the amino acid sequences of the polypeptides displayed on phage were deduced. After GST-polypeptides fusion protein was constructed and expressed, its binding to P37 was determined by GST-pull down and Western blot. After 4 rounds of bio-panning, the enriched positive phage clones were identified by ELISA. Eighteen positive phage clones were sequenced and the peptide sequences were as follows. ACAPKPPWLC (12/18), RPLSIDPWSPHL (3/18), RPLSNDPWSPHL (1/18), QNMMSPIEGVRI (1/ 18) and WAPEKDYMQLMK (1/18). The results from GST-pull down and Western blot showed that peptide RPLSIDPWSPHL could interact with P37. The study will be helpful for identifying the protein reacting with P37. PMID- 22295708 TI - [In vitro experimental study of rat cardiomyocyte injury with targeting of perfluorocarbon lipid particles]. AB - The present study was to investigate in vitro the rat cardiomyocyte injury with targeting of home-made perfluorocarbon lipid particles with avidin-biotin interaction. Neonatal rat cardiomyocytes were cultured in vitro and divided into two groups: TNF-alpha activated group and non-activated group. Those in the TNF alpha activated group were exposed to 200 ng/ml TNF-alpha solution for 6 hours and then cardiomyocytes in both groups were pretargeted with biotinylated ICAM-1 monoclonal antibodies, and were exposed to streptavidin, and then to homemade green fluorescently-labeled biotinylated perfluorocarbon lipid particles. Cardiomyocytes nucleus stained with Hoechst. The results were detected with fluorescence microscope. As a result, in TNF-alpha activated group, around blue fluorescent cardiomyocytes nucleus, a great amount of green fluorescent particles were found, while there were few green fluorescent particles in non-TNF activated group. It has been shown that ICAM-1 is expressed in the surface of cardiomyocytes when they are stimulated by TNF-alpha. Perfluorocarbon lipid particles associated with ICAM-1 monoclonal antibodies can be targeted to injured cardiomyocytes by avidin-biotin interaction. PMID- 22295709 TI - [Induced differentiation of human umbilical cord mesenchymal stem modified by cells Pdx1gene into islet beta-like cells in vitro]. AB - This study was to explore the induced differentiation of human mesenchymal stem cells (MSCs) modified by pancreatic and duodenal homeobox factor 1 (Pdx1) gene into insulin-producing cells in vitro. After recombined adenovirus vector with Pdx1 gene infected MSCs for 7 d, cells were induced by induction factors. The genes' expressions related to islet beta cells such as Pdx1, insulin, glucose transporter-2 (Glut2), were detected with RT-PCR, immunocytochemistry and Western blot. The levels of insulin and C peptide secretion were examined with chemiluminescence immunoassay. Insulin(+) cell rate was detected by flow cytometry. After infected by recombined adenovirus with Pdx1 and combined with induction factors, MSCs were aggregated and islet-like cell clusters formed. Dithizone staining of these cells was positive. The genes' expression related to islet beta cells, such as Pdx1, insulin, Glut2, could be detected. After induction, the islet-like cell clusters secreted insulin and C peptide. The levels of insulin and C peptide secretion increased with glucose stimulation. Insulin(+) cell rate was (11.61 +/- 4.83)%. It could be concluded that Pdx1 gene modified MSCs from human umbilical cord could be induced to differentiate into islet beta-like cells. PMID- 22295710 TI - [Preparation and identification of monoclonal antibody against alpha momorcharins]. AB - Three BALB/c mice were immunized four times with alpha-momorcharins (alpha-MMC). Using polyethylene glycol (PEG) method, the immunized splenocytes were fused with SP2/0 cells. One strain of hybridoma cells was obtained which secrete antibodies against alpha-MMC. To get ascites, the hybridoma cells were injected into the abdominal cavity of mice. The antibodies were purified from ascites. Indirect enzyme linked immunosorbent assay (ELISA) and Western blot assay were applied to determine the specifity of the monoclonal antibody (McAb). The results showed that the McAb was specific to alpha-MMC without detectable cross-activity with MAP30. The McAb provided detecting method for further research of the structure and function of alpha-MMC. PMID- 22295711 TI - [Effects of 131I therapy on peripheral blood in children and adolescents with differentiated thyroid carcinoma]. AB - The objective of this work was to observe the side effects on the peripheral blood treated with 131I in children and adolescents with differentiated thyroid carcinoma (DTC). The levels of white blood cells (WBC), neutrophil, HGB (hemoglobin), RBC (red blood cells) and the PLT (platelet) were measured by automatic hemocyte analyzer in 31 young enrolled patients (< or = 20 years old) before 131I therapy, 1 month and 6 months after 131I therapy, and at the end of follow up. The results of 131I treatment at the before and after the treatment were compared. The level of PLT decreased obviously (P < 0.01), WBC, RBC and HGB decreased (P < 0.05), neutrophil increased slightly (P > 0.05) 1 month after 131I therapy. The level of WBC, neutrophil, RBC, HGB and PLT were near to the level of before treatment after 6 months (P > 0.05) of 131I therapy. At the end of follow up, the components of the peripheral blood in the high dose group (7.4GBq 11.1GBq) were not significantly different from those at the beginning. The results showed that, there was only a transient impact on the peripheral blood by the 131I therapy in the children and adolescents with differentiated thyroid carcinoma. PMID- 22295712 TI - [A method for generating dental panoramic radiographs from 3D CT sectional data]. AB - In this paper, a new method was presented which can generate dental panoramic radiographs from the 3D CT sectional data. The dental panoramic radiograph was generated by casting ray into the 3D sectional data from a curved surface close to the dental arch. With this method, the relationship between the 3D CT sectional data and the dental panoramic radiographs was built, which helped to overcome the defects in the real X-ray panoramic radiographs, such as structure overlap and unselectable content for displaying. The technology is of certain significance in computer aided technique and surgical planning related to dentistry. PMID- 22295713 TI - [A new algorithm for affine motion compensation in PROPELLER MRI based on image domain]. AB - Affine motion is common during PROPELLER magnetic resonance imaging (MRI) in abdomen or other soft tissues. The current algorithm, up till now, for affine motion compensation is based on frequency domain, which compensates the motion in k space and then reconstruct the final image based on gridding method. But aliasing and some tiny artifacts may exist. This paper proposed a new algorithm for affine motion compensation based on image domain. Firstly, exact affine motion information was obtained through the image registration, secondly k space coordinate was corrected for compensating the k space strips sampling density, then the images obtained from inverse FFT was compensated using motion information, finally the final results were composited after rotation. The experimental results showed that the proposed method could more effectively suppress the motion artifacts compared to the current algorithm. PMID- 22295714 TI - [Modeling of electrophysiology and simulation of ECG under ischemic condition in human ventricular tissue]. AB - In this paper, to analyze the functional influence of ischemia on cardiac cell electrical activity and subsequently on ventricular electrical wave conduction, a human ventricular ischemic model was developed, which took into account three major pathophysiological components of ischemias hyperkalaemia, acidosis, and anoxia. This model simulated the action potential (AP) propagations of endocardial, midmycardial and epicardial cells with different levels of ischemia, and the influence of each factor on cell AP was analyzed. Finally the ECG waveform under ischemia was quantified by using a 2D model of human left ventricular tissue based on the anatomical structure of human heart. The experimental results showed that under ischemia action potential durations (APD) were reduced. In most cases, the larger the size of ischemic region or the more severe the ischemic level, the more dramatic the changes in the amplitude of ST-T wave were observed. For the three components of ischemia, hyperkalaemia was the dominant contributor to ST-T wave changes, which was in agreement with the results obtained on animal models. PMID- 22295715 TI - [Spectral analysis and LDB based classification of heart sounds with mechanical prosthetic heart valves]. AB - Auscultation, the act of listening for heart sounds to aid in the diagnosis of various heart diseases, is a widely used efficient technique by cardiologists. Since the mechanical prosthetic heart valves are widely used today, it is important to develop a simple and efficient method to detect abnormal mechanical valves. The study on five different mechanical valves showed that only the case of perivalvular leakage could be detected by spectral estimation. Though it is possible to classify different mechanical valves by using time-frequency components of the signal directly, the recognition rate is merely 84%. However, with the improved local discriminant bases (LDB) algorithm to extract features from heart sounds, the recognition rate is 97.3%. Experimental results demonstrated that the improved LDB algorithm could improve classification rate and reduce computational complexity in comparison with original LDB algorithm. PMID- 22295716 TI - [A classification method of gene expression profile based on a locally linear embedding algorism with improved distance]. AB - With its high dimensionalities, small samples and great noise, feature reduction of gene expression profile becomes quite necessary. The most common form of gene expression profile is nonlinear, and traditional dimensionality reduction methods can not project high dimensional data, whose initial dimensionalities are low, into low dimensional space. In this work, an improved distance locally linear embedding (LLE ) algorism was proposed to reduce the dimensionalities. LLE method is very sensitive to the closely-neighboring parameters. In order to enhance the robustness to the number of neighbors, in the paper we presented a novel distance to measure the distance between the samples for the purpose of reducing-the influence of distribution of samples. Experimental results demonstrated that the improved distance LLE can effectively extract information of classification features and greatly reduce the dimensionalities of data while maintaining a higher classification accuracy. PMID- 22295717 TI - [Activin A and BMP-4 induce cardiomyocyte-like cells differentiation of human amniotic epithelial cells]. AB - Amniotic epithelial cells (AECs) have been expected to be a good cell source for stem cell-based cardiac repair. Activin A signaling is required for cardiac differentiation in human embryonic stem cells (ESCs), and bone morphogenetic protein-4 (BMP-4) is an important regulator that controls stem cell fates. Previous study has established an efficient protocol to generate cardiomyocytes from human ESCs via induction with Activin A and BMP-4. The aim of present study was to test the hypothesis that Activin A and BMP-4 could also induce AECs to differentiate into cardiomyocytes in vitro. Human AECs (hAECs) were isolated from human term placenta by trypsin digestion according to the previous reports. Freshly isolated hAECs were examined to detect the expression of cytokeratin 19 by immunocytochemistry. High-density undifferentiated hAECs at passage 1 were sequential treated with 100 ng/ ml human recombinant Actvin A and 10 ng/ml BMP-4. The expression of cardiac-specific genes was examined before and after in vitro induction of cellular differentiation. Freshly isolated hAEC could express cytokeratin 19, the specific marker of epithelial cells. The data showed that hAECs treated with Activin A and BMP-4 were able to express cardiac-specific genes, including Nkx2.5 and alpha-actinin. Our results demonstrated that Activin A and BMP-4 could induce cardiomyocyte differentiation of hAECs, which might be a novel approach to induce differentiation of AECs into cardiomyocytes-like cells. PMID- 22295718 TI - [Research on algorithm of independent component analysis with two channel electrocardiograms]. AB - According to the independent component analysis (ICA) theory, in order to seperate the fetal electrocardiograms (FECG) from the observed data, we must use the larger number of observed signals than that of independent components. This requires that the number of the sentors on the electrocardiograph must be larger than a particular value, which is in practice hard to be satisfied. So we proposed another algorithm using fewer channels of abdominal electrocardiograms, which combines ICA and adaptive noise cancellation to extract the FECG from two leads of abdominal electrocardiograms. The experiment results showed that we could obtain clear FECG by the method we proposed. PMID- 22295719 TI - [Research progress of quantitative analysis for respiratory sinus arrhythmia]. AB - Respiratory sinus arrhythmia (RSA) is known as fluctuations of heart rate associated with breathing. It has been increasingly used as a noninvasive index of cardiac vagal tone in psychophysiological research recently. Its analysis is often influenced or distorted by respiratory parameters, posture and action, etc. This paper reviews five methods of quantification, including the root mean square of successive differences (RMSSD), peak valley RSA (pvRSA), cosinor fitting, spectral analysis, and joint timing-frequency analysis (JTFA). Paced breathing, analysis of covariance, residua method and msRSA per liter tidal volume are adjustment strategies of measurement and analysis of RSA in this article as well. At last, some prospects of solutions of the problems of RSA research are given. PMID- 22295720 TI - [The application progresses of the two dimensional electrophoresis in biomedical research]. AB - Research about proteomics is of great significance. Two-dimensional electrophoresis (2-DE) is a core technology of proteomics research, which is used for analysis of the protein extracted from cell, tissue and other sam-nology of proteomics research, which is used for analysis of the protein extracted from cell, tissue and other samples. In recent years, 2-DE combined with mass spectrum (MS) technology is widely used to identify differentialples. In recent years, 2 DE combined with mass spectrum (MS) technology is widely used to identify differential protein, to screen tumor markers, to detect drug targets and so on. Proteomics research has become key technology,protein, to screen tumor markers, to detect drug targets and so on. Proteomics research has become key technology, with its high throughput, high resolution and repeatability, and is widely used in various fields, particularly in bio-with its high throughput, high resolution and repeatability, and is widely used in various fields, particularly in biomedical research. We provided here a short review about the application development of 2-DE, especially its contribution on biological medicine. PMID- 22295721 TI - [Advances of research of hydrophilic/hydrophobic surface effect on cell biologic behaviors in vitro]. AB - Hydrophilicity/hydrophobicity, the same as chemical signals and mechanical stimuli, is an important characteristic of material surface, induces a cascade events of intercelluar proteins and genes, and determines cells biologic behaviors in vitro eventually. In this review, we summarize the available reports to review the methods of hydrophilic/hydrophobic surface modification, and its effects on protein adsorption and cells biologic behaviors. PMID- 22295722 TI - [Application of field-effect transistor based on carbon nanotube in biosensors]. AB - With the emergence of avian flu, influence A virus and other diseases, the development of rapid, real-time, label-free biological sensors has become increasingly significant at the early detection and clinical diagnoses of various diseases. Single-walled carbon nanotubes (SWNTs) have unique one-dimensional structure, special electrical properties, good biocompatibility and size compatibility, so that the SWNTs have great potential uses in the biosensor fields due to these advantages. This article reviews recent examples of carbon nanotubes field-effect transistor (CNTFET) as a label-free biosensors for detecting a variety of biological macromolecules, such as protein, enzyme, DNA, cancer, virus, carbohydrate and so on. PMID- 22295723 TI - [Corrosive degradation of magnesium and its alloy as endovascular stent]. AB - Magnesium and its alloy are used for the most potential endovascular stent material due to their excellent mechanical capabilities, adjustable corrosive properties, the little side effects of the materials and their degradation products. The in vito degradation rate of the current magnesium and its alloy as endovascular stent is very quickly so that the artery is not supported long enough to prevent negative remodeling. This review detailed the approach to enhance the corrosion resistance, in vitro corrosion rate measurement of magnesium and its alloy, as well as the in vito corrosion research when as the endovascular stents. PMID- 22295724 TI - [Research progress of tumor cell migration strategy and the migration transition mechanism]. AB - Tumor cells exhibit two main different migration strategies when invading in 3D environment, i. e. mesenchymal migration and amoeboid migration. This review summarizes the internal reasons and characteristics on various modes of migration adaptation to the microenvironment, and the molecular mechanisms in particular environment where they are mutually interchangeable. A study of the mechanisms that may possibly trigger mesenchymal-amoeboid transition/amoeboid-mesenchymal transition help us to understand the change and the plasticity in the migration strategies of tumor cells. These are important for the development of a cancer treatment, which would efficiently suppress tumor cell invasiveness. PMID- 22295725 TI - [Research progress in the relationship between heart development and cell apoptosis]. AB - The development of heart is an accurate, coordinated process including primordial cardiac cell differentiation, migration, and multi-cell combination. This process is accompanied by cell apoptosis, and by a series of gene regulation. If gene gets out of regulation, abnormal cell apoptosis will occur, which will lead to abnormal development of embryonic heart, or even malformation. By studying gene expression on apoptosis, we investigated the relationship between apoptosis and embryonic heart development, clarified the relevant mechanism for the clinical diagnosis and treatment of heart diseases. PMID- 22295726 TI - Adjunctive corticosteroid therapy in 149 grade II (non-shock) adult DHF patients: an analysis during January 2008-February 2010. AB - BACKGROUND: It is well known that immunopathogenesis play an important role in the development of severe complications in DHF. Since 2006, the authors have experience in giving immunomodulators to save life of many severe complicated adult DHF patients. This experience stimulates our interest on the benefit of adjunctive corticosteroid therapy in adult grade II DHF patients. OBJECTIVE: To find out whether there are some benefits of giving adjunctive corticosteroid therapy in adult grade II DHF patients. DESIGN OF THE STUDY: Retrospective analysis during January 2008-February 2010. MATERIAL AND METHOD: One hundred and forty nine adult grade II DHF patients were admitted at Vichaiyut Hospital. They were divided into 3 groups according to the different therapy designed by the responsible clinicians. Group 1 consisted of 59 cases who received full dose short course of intravenous dexamethasone (4 milligram every 6 hours for 2-3 days). Group 2 consisted of 61 cases who received intermittent 4 milligrams intravenous dexamethasone only at febrile episode and group 3-29 cases did not received corticosteroid. All the patients were investigated similarly. Age, sex, symptoms and signs including daily hematologic studies (Hct, Wbc, differential count, platelet count) were recorded. Serum SGOT SGPT bilirubin, alkaline phosphatase and albumin BUN, creatinine were performed on admission and repeated as indicated. The parameter to measure the benefit of adjunctive corticosteroid included 1) severity of thrombocytopenia, 2) liver impairment, 3) the days of illness as determined by fever and 4) the length of the hospital days. RESULTS: The clinical severity of all the three groups were quite similar. There was no benefit of using adjunctive corticosteroid therapy in term of changing the severity of thrombocytopenia and liver impairment. However, the days of illness and the length of hospital days were shorter at 4.6 days and 3.7 days respectively in the group who received full dose, continuous-short course of dexamethasone intravenously. This is statistically significant when compared to the other two groups who had the longer total days of fever at 5.8 days and 6.03 days and the longer length of hospital days at 5.19 days and 4.5 days respectively (p < 0.05). CONCLUSION: Adjunctive corticosteroid by given full dose, continuous short course in grade II adult DHF reduced the course of illness (days of fever) and the length of hospital days. These findings indicated the benefit of using adjunctive corticosteroid therapy in grade II adult DHF patients. PMID- 22295727 TI - Lipid-lowering treatment in hypercholesterolemic patients: the CEPHEUS Thailand survey. AB - BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) has become the leading cause of death and disability in Thailand. Low-density lipoprotein cholesterol is the major risk factor of this condition that can be intervened by means of lifestyle modification and pharmacologic treatment. Adequacy of hypercholesterolemia treatment with lipid lowering drugs in Thailand needed to be more clarified. The present study was conducted to determine low-density cholesterol goal attainment in Thai population at risk for developing ASCVD. MATERIAL AND METHOD: Twenty-seven physicians with their 909 hypercholesterolemic patients whose age of > or = 18 years, actively under pharmacologic treatment for at least three months with no dose adjustment for a minimum of six weeks from seven centers across Thailand were enrolled. Plasma glucose, total cholesterol, LDL cholesterol, HDL-cholesterol, and triglyceride levels were measured after overnight fast. Demographic and other relevant data including information on lipid lowering drug used were retrieved. Patients' awareness, knowledge on their management, compliance, and satisfaction were evaluated by questionnaire survey as well as physicians' use of guidelines, choice of management and goal setting, and their attitudes towards lipid management. Cardiovascular risk level and LDL goal were assessed by the updated 2004 NCEP-ATP III guidelines. RESULTS: All patients had LDL goal of < 130 mg/dl with 86.1% needed LDL goal of < 100 mg/dL. Overall, 52.7% of the patients reached their LDL goal. The most prescribed treatment was statin monotherapy (82.7%). LDL goal attainment was inversely associated with LDL goal set by NCEP-ATP III according to the patients' risk profile, with only 16.7% of those who were in the very high risk group with LDL goal of < 70 mg/dL achieved their goal whereas 60.6% and 84.7% of those with high (LDL goal < 100 mg/dl) and moderately high-risk (LDL goal < 130 mg/dl) achieved their goal, respectively (p < 0.001). Other factors associated with less favorable LDL goal attainment were coronary heart disease, carotid artery disease, diabetes, 10-year risk of > 20%, and metabolic syndrome (p < 0.05 for all). Type of lipid lowering drug was not significantly associated with LDL goal attainment. CONCLUSION: LDL goal attainment was not achieved in a high proportion of Thai patients especially in those who had high to very high risk for developing cardiovascular disease. Despite availability of well-established treatment guideline and efficacious lipid lowering drugs, many patients still miss the opportunity to effectively control their lipid profile. PMID- 22295728 TI - Severe hypoglycemia in type II diabetes at Nakornping General Hospital: a study on clinical risk factors. AB - OBJECTIVE: To study clinical risk factors of severe hypoglycemia in type II diabetes. MATERIAL AND METHOD: Fifty-one type II diabetes with severe hypoglycemia admitted between October 2006 and September 2008 and 359 nonhypoglycemic type II diabetes were evaluated in this case-control study. Medical records were retrospective reviewed for age, sex, duration of diabetes, previous diabetes registration, concomitant diseases, HbA1c level and current diabetes therapy in both groups. Acute illness, blood glucose, hypoglycemic episodes, symptoms and length of stay (LOS) were assessed in hypoglycemic group. Univariate and multivariate logistic regression were used to determine risk factors of severe hypoglycemia. RESULTS: Fifty-one hypoglycemic and 359 nonhypoglycemic patients were analyzed. The authors found that 40% of severe hypoglycemic cases were recurrent. The average LOS was six days. Intercurrent illness was the major leading cause of hypoglycemia (54.9%). Mean blood glucose level was 37.2 mg/dl (SD = 13.5). Twenty-three of fifty-one (45%) patients presented with unconsciousness. Predisposing risk factors associated with severe hypoglycemia were old age (p = 0.026), insulin therapy (p = 0.001), cirrhosis (p = 0.020), cerebrovascular disease (p = 0.040), and no diabetes registry (p = 0.015). Sex, HbA1c level, hypertension and chronic kidney disease were not risk factors associated with severe hypoglycemia. CONCLUSION: Risk factors associated with severe hypoglycemia in type II diabetes were elderly, insulin therapy, cirrhosis, previous cerebrovascular disease, lack of standard diabetic care and team approach. Self-monitoring of blood glucose and individual case management should be considered in those with previous hypoglycemic events. PMID- 22295729 TI - Infant toilet training in Thailand: starting and completion age and factors determining them. AB - OBJECTIVE: To study the age at which Thai infants start and achieve toilet training and its associated factors. MATERIAL AND METHOD: The parents of fifty infants in a research entitled "Bowel movements of normal Thai infants" were interviewed about age at which toilet training started, the process of toilet training and age at which infant successfully completed toilet training. RESULTS: Forty-seven infants from the 50 infants registered had data of the date of beginning toilet training. Five of them (10.6%) started toilet training at 4 months and 38 (80.9%) by 12 months. Most of the infants (73.7%) were initially trained when they showed urging signs. Only 45 infants had complete data of successful toilet training. Twenty-two cases (48.9%) were trained successfully by 12 months and most of them (16/22) succeeded within one month. The infants, who were not the first child and were taken care of by a well-educated mother, were found to start toilet training late. CONCLUSION: The youngest age at which normal Thai infants start to be toilet trained was 4 months. About 50% of the infants aged 12 months had successful toilet training. Being raised by a well-educated mother and a having a later birth order in a family were factors associated with late toilet training. PMID- 22295730 TI - The rising incidence of type 1 diabetes in the northeastern part of Thailand. AB - OBJECTIVE: To determine the incidence of T1DM in children under 15 years in 19 provinces in northeast Thailand. MATERIAL AND METHOD: Data of new cases of T1DM during 10 years between 1996 and 2005 were collected retrospectively by a mail survey from 275 hospitals in northeast Thailand. RESULTS: Three hundred forty cases, 134 (39.4%) boys and 206 (60.6%) girls were identified. The incidence rate of T1DM was 0.6/100,000/year (95% confidence interval 0.57; 0.71), a two-fold increased from the previous study between 1991 and 1995. More than half of the cases were diagnosed between the ages of 10 and 14 and the incidence rate in girls was 1.5 fold that of boys. CONCLUSION: Though the increased in incidence rate, the study indicated that the incidence of T1DM in northeast Thailand is still one of the very low incidence rates in the world. PMID- 22295731 TI - Accuracy of needle-tip localization by ultrasound guidance lumbar selective nerve root block: a prospective clinical study of 78 lumbar nerve roots block. AB - OBJECTIVE: Selective nerve root block (SNRB) is the accepted procedure for diagnostic and therapy in lumbar radicular back pain management. The present study was to determine the accuracy of needle-tip under ultrasound guidance subsequently confirmed with fluoroscopy in patients who underwent SNRB. To date, no study comparing these two techniques has been performed. MATERIAL AND METHOD: After the IRB approval, a prospective trial was conducted to determine the accuracy of ultrasound guidance SNRB in 40 consecutive patients with lumbar radicular pain undergoing fluoroscopic guidance SNRB between January 2010 and January 2011. Firstly, needle-tip was located at the desired optimal landmark under ultrasound guidance and then subsequently fluoroscopic confirmation of needle-tip position was done. Finally, the injection was performed as usual. The primary outcome was the accuracy of needle-tip placement comparing between under ultrasound and subsequently fluoroscopic confirmation. The secondary outcome was the associated factors of the accuracy of needle-tip under ultrasound guidance. RESULTS: Seventy-eight lumbar nerve roots were injected in the patients that underwent SNRB under fluoroscopic guidance. The accuracy of needle-tip on each lumbar nerve root under ultrasound guidance with fluoroscopic confirmation ranged from 7.14% to 80.95%. Mean of the accuracy of needle-tip under ultrasound guidance comparing with subsequently fluoroscopic confirmation was 62.82% while 95% CI ranged from 51.13 to 73.50%. The age older than 65 years old was significantly associated with the poor accuracy under ultrasound guidance (p value = 0.0095). CONCLUSIONS: To position the needle-tip under ultrasound guidance is feasible and has good safety profile. The accuracy could be achieved individually. However, because the accuracy of ultrasound guidance technique depends on the operator a steep learning curve and larger prospective clinical study is needed. PMID- 22295732 TI - Chronic arterial embolism of the lower extremities: an unusual etiology of critical limb ischemia. AB - BACKGROUND: Chronic arterial embolism of the lower extremities, the unusual cause of critical limb ischemia (CLI), is not well recognized in the medical practice. OBJECTIVE: To study the clinical problem of chronic arterial embolism in the aspects of the clinical characteristics and treatment outcomes. MATERIAL AND METHOD: Between January 2000 and December 2004, 411 consecutive patients with chronic limb ischemia, including 16 (3.8%) patients with chronic arterial embolism were included in the present study. The diagnosis of chronic arterial embolism was confirmed by angiography, operative finding, and histopathology of amputated specimen. The clinical characteristics and management outcomes were recorded and analyzed. RESULTS: Of the 16 patients with chronic arterial embolism, the mean duration of clinical manifestation was 2.4 months (range, 1 6). Femoral artery was the most common site of arterial occlusion (63.1%). Atrial fibrillation was the most common clinical risk factor (25.0%). Of the 14 patients (87.5%) suffering from CLI, nine patients (56.25%) underwent the various types of revascularization. In five patients (31.25%), the authors could not perform revascularization due to the fibrotic arteries. Successful limb salvage and disappearance of rest pain with complete healing of ulcer in patients with CLI were only 50%. One patient (6.25%) expired after major amputation. CONCLUSION: Chronic arterial embolism of the lower extremities is the unusual cause of CLI with a high rate of major amputation. Early detection and appropriate management of arterial embolism at the initial stage may reduce this serious vascular problem. PMID- 22295733 TI - Full endoscopic lumbar discectomy via interlaminar approach: 2-year results in Ramathibodi Hospital. AB - OBJECTIVE: To present the surgical outcome of the full-endoscopic lumbar discectomy via interlaminar approach. MATERIAL AND METHOD: Analysis of the prospectively collected data. The indication for full endoscopic discectomy is the same as for microscopic discectomy. Sixty consecutive patients with lumbar disc herniation were included. Full-endoscopic discectomy via interlaminar approach were done in all cases. The Visual analog scale (VAS), Thai version of modified Oswestry Disability Index (ODI), Macnab score, neurological symptoms, and complications were collected and followed for two years. RESULTS: Mean follow up period was 26 months. Excellent outcomes as defined by Macnab criteria were found in fifty-five of sixty patients (91.6%). The authors found two cases of recurrent disc herniation, which were re-operated by the same method and the symptoms were completely resolved later in the follow up period. There were two cases of persistent radicular pain after the operation, which were completely resolved after selective epidural nerve root injection. There was no serious neurological deficit, dura tear, or cauda equina syndrome in the present study series. CONCLUSION: Full-endoscopic lumbar discectomy is a safe and effective procedure for lumbar disc herniation. Patients can expect less postoperative pain, early recovery, and a short period of work absence. However, the learning curve is steep. Proper surgical training and careful patient selection in the early cases are the keys to success. PMID- 22295734 TI - Outcome predictor of spontaneous intracerebral hemorrhage management: ten-year neurosurgical experience at Ramathibodi Hospital. AB - OBJECTIVE: To determine the one-year outcome predictor for spontaneous intracerebral hemorrhage (sICH) patient population admitted to the Division of Neurosurgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University Bangkok, Thailand. This was also to provide a better understanding to assist physicians and caregivers in evaluating sICH survivors during this first year after treatment. MATERIAL AND METHOD: The authors reviewed brain computed tomographic films and medical records of all sICH cases admitted at Ramathibodi Hospital, Mahidol University between 1999 and 2009. One-year outcome predictors were determined using multiple logistic regression statistical analyses. RESULTS: There were 537 cases with sICH diagnosis between 1999 and 2009. However 239 cases were collected after online medical record review and 138 completed medical record files were retrieved. Modified Rankin Scale (mRS) was used to determine the authors' outcome treatment and categorized into two groups. The crucial group (mRS 5 and 6) and the favored group (mRS < 5) were compared. Volume of sICH and Initial hospitalization Glasgow Coma Scale were the significant predictors of one year treatment outcome for all locations of sICH. Using two classifications of intracerebral hemorrhage volume (less than 30 cc, and more than 30 cc) and three categories of the Glasgow Coma Scale (13-15, 9-12, and 8 or less), one year treatment outcome was predicted correctly with odd ratio and 95% confidence interval. CONCLUSION: Volume of sICH and initial hospitalization Glasgow Coma Scale is significantly influential to be one-year predictor in patients with sICH. The expectation of the treatment has to be discussed and planned for long term management. PMID- 22295735 TI - A new alternative to quantify finger rotation: angles between the axis of flexed fingers and the axis of third metacarpal bone. AB - OBJECTIVE: To determine whether the proposed angle, formed between the axis of middle and distal phalanges of each of flexed fingers and the axis of the third metacarpal bone was symmetrical between both hands in adult population. MATERIAL AND METHOD: Thirty-one volunteers (12 males and 19 females) having normal and uninjured hands with an average age of 38 years underwent a fluoroscopic examination of their hands. All volunteers put their hands in a special positioning device that passively held the metacarpophalangeal and proximal interphalangeal joints in full flexion with distal interphalangeal joint in full extension. Fluoroscopic images were then taken and angles were digitally measured. RESULTS: Mean angles of the flexed index, middle, ring and small fingers compared to the third metacarpal bone were -4.07 (SEM = 1.041), 5.22 (SEM = 0.889), 12.91 (SEM = 1.009) and 23.11 (SEM = 1.370) degrees, respectively. The angles were statistically symmetrical between both hands (p = 0.838, 0.546, 0.620 and 0.641, respectively). The genders had no effect on the symmetry (p > 0.3). The differences between angle of each finger and the angle of the middle finger were also found to be statistically symmetrical. CONCLUSION: Side-to-side comparison of the angle formed between the axis of flexed fingers and the third metacarpal bone measured from radiographic images can be used as an additional alternative to determine the finger rotation. The angular relationship between each finger with respect to the middle finger can also be used to purposefully reduce x-ray beam projection variation. PMID- 22295736 TI - Efficacy of gentle traction, abduction and external rotation maneuver under sedative-free for reduction of acute anterior shoulder dislocation: retrospective comparative study. AB - BACKGROUND: Reduction technique of acute anterior shoulder dislocation is always performed under sedation or general anesthesia in order to permit successful reduction such as traction counter-traction (TCT). However, the patients take risks of sedation or anesthesia. There are several techniques of reduction that reduce the dislocation without using sedation or anesthesia such as Milch technique, gentle traction, abduction and external rotation (TAE) technique and scapular manipulation. In the present study, the authors compared efficacy of reduction of acute anterior shoulder dislocation by using TAE without sedation and TCT techniques under conscious sedation. OBJECTIVE: To compare efficacy of TAE without sedation and TCT techniques under conscious sedation for reduction of acute anterior shoulder dislocation. MATERIAL AND METHOD: Between 2001 and 2010, the authors reviewed medical records and radiographs of 76 patients who sustained one or more episodes of acute anterior shoulder dislocation and divided into two groups. Group 1 used the technique of TAE without sedation. Group 2 used the technique of TCT under conscious sedation. Group 1 and 2 consisted of 32 and 44 patients, 24 and 33 males, eight and 11 females, average age 39.13 (17-71) and 34.77 (18-76) years old, 24 and 34 right sides, eight and 10 left sides, 21 and 24 from sport injuries and 10 and 18 non-sport injuries respectively. Successful reduction, post-reduction complication and patients 'satisfaction score of 0 to 10 of both groups were evaluated and p < or = 0.05 were considered for statistical significant differences. RESULTS: The successful reduction of group 1, 2 were 90.63% (29/32) and 100% (44/44) with 95% Confidence interval 74.98 to 98.02% and 93.42 to 100% respectively. The statistical analysis showed no significant difference of both groups (p = 0.071). There was no post-reduction complication of both groups. The patients' satisfaction score of group 1, 2 were 9.38 (8-10) and 7.94 (3-10). The statistical analysis showed patients' satisfaction score of group 1 were significantly higher than group 2 (p = 0.007). CONCLUSION: TAE technique under sedative-free for reduction of acute anterior shoulder dislocation is effective, simple, and safe. PMID- 22295737 TI - Functional outcome after decompression and instrumented arthrodesis in degenerative lumbar spinal stenosis: factors influencing unsuccessful outcome change. AB - OBJECTIVE: To determine functional outcome after decompressive laminectomy and instrumented arthrodesis in patients with degenerative lumbar spinal stenosis and identify predictors of failed clinical outcome in these patients. MATERIAL AND METHOD: A retrospective cohort data were collected from January 1999 to February 2004. Degenerative lumbar spinal stenosis patients who had decompressive laminectomy and instrumented fusion with pedicular screw system and completed at least 2 years follow-up were enrolled in the present study. Outcomes included Oswestry Disability Index (ODI), Roland Morris score and patient satisfaction. Factors evaluated as outcome variables were age, gender onset, patient income, associated diseases, smoking, diagnosis of spondylolisthesis or scoliosis, number of levels of instrumentation and presence of S1 fusion. Univariate analysis for factors influencing failed clinical outcome used Chi-square and Fisher exact test and multivariate analysis used the logistic regression. RESULTS: One-hundred and fifty-eight patients were included in the present study. Mean follow-up was 2.64 years (range, 2-5 years). The mean age of the patients at the time of surgery was 60.3 years (range, 34-87 years) and 129 cases (81.7%) were female. According to the US FDA, the criteria of significant successful clinical outcome change is reduction of ODI at least 15%, the proportion of patients reporting significant successful clinical outcome change was 63.9%. Multivariate analysis identified age > 65 years, onset > 24 months and number of levels of instrumentation > 4 as the factors of failed clinical outcome change (p < 0.05). CONCLUSION: Decompression and instrumented arthrodesis in degenerative lumbar spinal stenosis gained satisfactory functional outcome. Older age, prolonged onset and long level of instrumentation were the factors of failed clinical outcome change. PMID- 22295738 TI - Therapy of idiopathic sudden sensorineural hearing loss with intratympanic steroid injection. AB - OBJECTIVE: To evaluate the efficacy of intratympanic steroid injection in patients with idiopathic sudden sensorineural hearing loss (SSNHL) who are not responding to systemic steroids. MATERIAL AND METHOD: A prospective cohort study of 31 patients, with idiopathic SSNHL refractory to oral steroid therapy, who were treated with intratympanic steroid injection. The injections were performed once a week for three consecutive weeks. Pure tone audiometry (PTA) and speech discrimination score (SDS) was performed before and two months after intratympanic steroid injection had been completed. Successful treatment was defined as a decrease in PTA by 10 dB or more, or an increase in SDS by 20% or more. RESULTS: Thirty-one patients were treated with intratympanic steroid injection, 22 women and 9 men. The average age was 53 years. Overall success was 14 patients (45.2%). Eleven of the patients (35.5%) showed either improvement in PTA or SDS, among these there were two patients who had improvement in only PTA and nine patients had improvement only in SDS. Besides, three of the patients (9.7%) had improvement in both PTA and SDS. CONCLUSION: Intratympanic steroid injection effectively improves hearing in patients with SSNHL after treatment failure with oral systemic steroid and is not associated with side effects. Therefore, it can be used as salvage therapy after failed conventional treatment. Further studies are required to consider whether intratympanic steroid injection might be used as the first line treatment in SSNHL. PMID- 22295739 TI - Incidence of the accessory internal thoracic artery and its safety area in the thoracic wall. AB - OBJECTIVE: To provide the incidence, origin, size and the safety area of the accessory internal thoracic artery (AITA) in the fourth intercostal space. MATERIAL AND METHOD: One hundred and thirty two thoracic cages were dissected and examined for the presence of AITA. The origin, course, diameter and location in the fourth intercostal space of detected AITA were investigated. RESULTS: AITA with diameter ranging from 0.6 to 3.05 (mean = 1.76 +/- 0.69) millimeters existed in 10 of 132 (7.58%) cadavers. They originated from the upper part of the internal thoracic artery, close and inferior to the subclavian artery (0-3 cm, mean = 2.4 +/- 0.78) and ran inferolaterally on the deep surface of the thoracic wall and ended in the second to the sixth intercostal spaces. Most of them ended in the fifth intercostal spaces (28.57%). The artery was present bilaterally in 4 cases (3.03%) and unilaterally in 6 cases (4.55%). Most of these arteries were located close to the midaxillary line (0-3 cm, mean = 1.73 +/- 1.18) in the fourth intercostal space which is endangered in several surgical procedures such as thoracoscopy. CONCLUSION: Even the incidence of AITA is low (7.57%) but when present, it is endangered in thoracic surgical procedures. The safety area of AITA for surgical procedures in the fourth intercostal space is at least 3 centimeters anterior to the midaxillary line. PMID- 22295740 TI - Molecular characterization of extended spectrum beta-lactamase among clinical isolates Escherichia coli and Klebsiella pneumoniae. AB - BACKGROUND: Resistance to beta-lactams has been increasing in the treatment of infections caused by Escherichia coli and Klebsiella pneumoniae. The production of extended-spectrum beta-lactamases (ESBLs), that hydrolyze extended-spectrum cephalosporins, is the major cause of beta-lactam resistance. OBJECTIVE: To determine the prevalence and characterize of ESBLs produced by E. coli and K. pneumoniae from clinical specimens. MATERIAL AND METHOD: ESBLs were determined by disk diffusion test, double disk synergy test, and E-test ESBLs. All ESBLs producing isolates were investigated for the presence of bla(TEM) bla(SHV), bla(CTX-M) and bla(VEB) genes by polymerase chain reaction (PCR). Nucleotide sequencing of bla(TEM) and bla(SHV) were performed E. coli and K. pneumoniae were isolated from clinical specimens of patients in King Chulalongkorn Memorial Hospital between February and May 2002. Of the 270 isolates, 212 were E. coli and 58 were K. pneumoniae. RESULTS: ESBL roduction was detected in 17% (36/212) of E. coli and 34.5% (20/58) of K. pneumoniae isolates. Of the 20 K. pneumoniae isolates, the beta-lactamase genes were bla(SHV) (18/20, 90%), bla(TEM) (10/20, 50%), bla(VEB-like) (6/20, 30%) and bla(CTX-M-like) (3/20, 15%). Thirty-six E. coli isolates carried bla(TEM) bla(CTX-M-like) and bla(VEB-like) genes in 72.2% (26/36), 52.8% (19/36) and 16.7% (6/36), respectively Bla(SHV) was not detected in ESBL-producing E. coli, whereas it predominated in K. pneumoniae. Of the 56 ESBL producing isolates, 30 (53.6%) coharboured at least two different bla genes. All TEM identified were TEM-1B, which is not an ESBL. CTX-M ESBLs were the most common in E. coli. CONCLUSION: The double disk diffusion test should be added routinely in the antibiotic susceptibility test for the Enterobacteriaceae. It is simple to perform, easy to interpret, and economical. The presence of bla(CTX-M) and bla(VEB) in ESBL-producing E. coli and K. pneumoniae indicates the high prevalence of these genes in Thailand. PMID- 22295741 TI - Factors associated with the effectiveness of diabetes care at primary care settings. AB - OBJECTIVE: To assess the effectiveness of diabetes care and the factors associated with the effectiveness at primary care settings. MATERIAL AND METHOD: Data were obtained from reviewing of 1,795 medical patient files of patients with type 2-DM treated at forty-eight primary care settings. Information recorded included characteristics, body mass index, co-morbidity, fasting blood glucose (FBG) and HbA1c levels and health personnel mix types (physicians, pharmacists, nurses, health technical officers and community health workers). HbA1c level of diabetes in 542 of 1,795 medical patient files were analyzed. Glycemic controllability of diabetes patients was defined using FBG and HbA1c levels as the effectiveness indicators of diabetes care. RESULTS: Of 1,795 patients, 40.8% were able to control their FBG levels and 22.7% of the 542 patients who have HbA1c data could control their HbA1c levels. Multivariate analysis confirmed that age and health personnel mix types are significant factors for glycemic controllability as measured by FBG level (p < 0.01). By measuring HbA1c level, age was also significant factor in diabetes care effectiveness (p = 0.012). CONCLUSION: Age was a significant factor in controlling both FBG and HbA1c levels in type 2 diabetes whereas health personnel, physicians and pharmacists, are significant factors in increasing effectiveness of diabetes care. The policy makers should consider distributing these health personnel to primary care settings and this would be a challenge for the policy makers to develop such a strategy and to implement this policy. PMID- 22295742 TI - Biomonitoring of heavy metals among nielloware workers in Nakhon Sri Thammarat Province. AB - OBJECTIVE: To determine lead and mercury concentrations in biological samples from nielloware workers, to describe the association between occupational lifestyle, workposition, work environment, behavioral factors, acute and chronic neurological symptoms, and levels of metals in biological samples. MATERIAL AND METHOD: A cross-sectional study was conducted by interviewing 45 nielloware workers and 45 matched nonexposed persons living in the municipality of Nakhon Si Thammarat Province, Thailand. Blood and urine samples were collected to determine lead and mercury concentrations by atomic absorption spectrophotometer. RESULTS: The blood lead levels (7.30 microg/dl) and urinary mercury levels (3.30 microg/g creatinine) of the nielloware workers were significantly higher than the control group (p < 0.001). Income, working environmental conditions, workposition, duration of work, personal protective equipment (PPE) and personal hygiene, had significant associations with blood lead and urinary mercury levels (p < 0.05). A significant positive correlation was found between income and blood-lead level (r = 0.968, p < 0.001) and urinary-mercury level (r = 0.661, p = 0.004). The nielloware workers developed acute and chronic symptoms, such as headaches, rash, fatigue, tightness in the chest, loss of consciousness, abnormal tiredness and headache at least once a week and those who developed symptoms had significantly higher heavy metal levels than those who did not at p < 0.05. CONCLUSION: The blood lead and urinary mercury levels in nielloware workers were significantly higher than those in the control subjects. The significant associations were found between income, work position, PPE and personal hygiene and blood lead and urinary mercury levels. PMID- 22295743 TI - Alterations in malondialdehyde levels and laboratory parameters among methamphetamine abusers. AB - OBJECTIVE: To determine the concentrations of malondialdehyde, biochemical, and hematological parameters among methamphetamine abusers compared with a healthy control group and to evaluate the association between malondialdehyde and biochemical-hematological parameters. MATERIAL AND METHOD: The concentrations of malondialdehyde, lipids, liver enzymes, albumin, blood urea nitrogen, creatinine, and hematological measurements were determined in 60 methamphetamine abusers and 60 controls. RESULTS: Significantly higher levels of malondialdehyde were found in the methamphetamine abusers than the controls [2.45 (2.12-2.81) vs. 1.41 (1.15 2.08)]. The levels ofalanine aminotransferase and alkaline phosphatase and white blood cell and platelet counts of the methamphetamine abusers were significantly elevated (p-value < 0.05) compared with the controls. Meanwhile, the levels of hemoglobin, hematocrit, albumin and body mass index were significantly lower among the methamphetamine-abusing group than the control group (p-value < 0.05). It was found that higher numbers of methamphetamine tablets per day were associated with higher malondialdehyde concentrations in methamphetamine abusers, and that malondialdehyde concentration inversely correlated with albumin level (r = -0.458, p-value < 0.05). Stepwise multiple regression analysis revealed that number of methamphetamine tablets per day, white blood cell count and albumin level were independent predictors of malondialdehyde level (p-value < 0.05). CONCLUSION: Methamphetamine abuse is related to increased lipid peroxidation, changes in inflammatory marker level, increase in liver enzymes, and decrease in hemoglobin and hematocrit concentrations. These effects may be early signs of the development of diseases associated with methamphetamine abuse. PMID- 22295744 TI - Comparative analysis of pathological and toxicological features of opiate overdose and non-overdose fatalities. AB - OBJECTIVE: To compare pathological and toxicological features between opiate overdose and non-opiate overdose fatalities examined in the Department of Forensic Medicine, Chiang Mai University, Thailand. MATERIAL AND METHOD: A retrospective study of 142 cases, diagnosed as opiate-related deaths between 1996 and 2008 was conducted. Demographic data, pathological findings and toxicological results were retrieved from autopsy records. RESULTS: Within these 142 opiate related deaths, 102 cases were classified as opiate overdose fatalities by Forensic Medicine doctors. More than 95% ofcases were male. About 80% were aged 20 to 39 years. Forty-eight percent were Thai, 13% were British and 11% were American. The most commonplaces of death were residential areas and hotels. Pulmonary edema and needle marks were more common in opiate overdose cases than in non-opiate overdose cases. Toxicological findings showed that 61% of opiate overdose cases and 34% of non-opiate overdose cases were positive for blood morphine. Morphine was detected in about 95% of urine samples in both groups. About 62% of opiate overdose cases and 31% of non-opiate overdose cases had positive blood alcohol. CONCLUSION: The average incidence of opiate-related death was about 1% of autopsy cases. More than two thirds of the deaths were opiate overdose cases. After the year 2003, more foreigners suffered from opiate overdose fatalities than Thais. The fatalities were confined to an area frequented by tourists. Pulmonary edema and needle puncture marks were more frequently observed in opiate overdose cases. The number of cases of morphine detection in serum from the opiate overdose group was significantly higher than in the non-opiate overdose group. There was no significant difference in urine morphine detection between both groups. Other substances detected in these victims were alcohol, benzodiazepines, methamphetamine, methylenedioxymethamphetamine and methadone. Alcohol was found significantly higher in opiate overdose fatality than in non-opiate overdose deaths. PMID- 22295745 TI - Cutaneous lymphoepithelioma-like carcinoma: report of three cases. AB - BACKGROUND: Cutaneous lymphoepithelioma-like carcinoma (cutaneous LELC) is an extremely rare malignant neoplasm with unclear histogenesis. Its histopathologic features are like those of lymphoepithelioma-like carcinoma occurring in the nasopharynx and in visceral organs especially salivary glands. MATERIAL AND METHOD: The authors reported on one male and two female patients of cutaneous LELC with immunohistochemical and electron microscopic study. All patients were of old age. All cutaneous LELCs in this report occurred on the patient's face, one of each on the eyelid, conjunctiva, and cheek. RESULTS: All resection specimens showed the typical histopathologic features of those of LELC, i.e. well defined tumor lobules mainly located in the dermis and extending into the panniculus. These tumor lobules typically displayed ill-defined clusters/nests of large epitheloid cells with pale eosinophilic cytoplasm, atypical vesicular nuclei possessing prominent nucleoli and were surrounded by dense lymphoplasmacytic infiltration. Immunocytohistochemically, these epitheloid cells showed epithelial differentiation by the expression of epithelial membrane antigen (EMA), P63, CK5/6 and CAM5.2 but were negative to CK20, CEA and Ebstein Barr virus (EBV). Squamous cell differentiation by the presence of desmosomes by electron microscopic study was also noted in two patients (case 1 and 3). CONCLUSION: The findings described above indicated that cutaneous LELC was a malignant neoplasm exhibiting squamous cell differentiation. PMID- 22295746 TI - Identification of conserved protein complexes by module alignment. AB - Recently, accumulating evidence suggests that biological systems are composed of interacting, separable, functional modules (e.g., protein complexes)--groups of vertices within which connections are dense while between which they are sparse. These functional modules always correspond to well-known protein complexes, which may be evolutionarily conserved across multiple species. Therefore, in this paper, we propose a method based on module alignment, which integrates protein interaction, and sequence information for finding conserved protein complexes. First, our method decomposes Protein-Protein Interaction (PPI) networks into modules by module detection methods, and then identifies conserved complexes by module alignment based on sequence similarity between pairs of proteins from each of the species. We test our method between Saccharomyces cerevisiae and Drosophila melanogaster. The results show that our method gets a higher accuracy for identification of conserved complexes. PMID- 22295747 TI - Analysis of the relationships among Longest Common Subsequences, Shortest Common Supersequences and patterns and its application on pattern discovery in biological sequences. AB - For a set of multiple sequences, their patterns, Longest Common Subsequences (LCS) and Shortest Common Supersequences (SCS) represent different aspects of these sequences' profile. Revealing the relationship between the patterns and LCS/SCS might provide us with a deeper view of the patterns. In this paper, we have showed that patterns LCS and SCS were closely related to each other. Based on their relations, the PALS algorithms are proposed to discover patterns in a set of biological sequences based on LCS and SCS results. Experiments show that the PALS algorithms are superior in efficiency and accuracy on a variety of sequences. PMID- 22295748 TI - Use experience evaluation of Google search for obtaining medical knowledge: a case study. AB - More and more people use internet search engines, especially Google, to learn about diseases and possible treatments. We conducted a hallway testing to evaluate the effectiveness of Google in obtaining medical information. We searched 'Breast Cancer' using Google. Six volunteers scored their experience for each of the top 500 websites. Our study shows that 50 hits of Google often help lay users in getting medical information, but some highly useful websites may be buried beyond top 200. Hence, the specificity of using Google in searching for medical information is satisfactory while the sensitivity of the search has significant room for improvement. PMID- 22295749 TI - A machine learning-based system to normalise gene mentions to unique database identifiers. AB - In this paper, we propose an integrated Gene normaliser (GNer) to assign a unique database identifier for each recognised gene mention in biological literature. The GNer combines Support Vector Machines (SVMs) and some rule-base components. First, we construct a dictionary from EntrezGene and BioThesaurus. Then we reduce variations and ambiguities of synonyms based on a designed pre-processor. Finally, a SVM-based disambiguation filter is developed to eliminate the ambiguity of exact matching. From the experimental results, the proposed GNer can achieve a fairly good performance, which can achieve the precision 80.5%, the recall 86.4% and the F(beta=1) measure 83.4. PMID- 22295750 TI - Detection and 2-dimensional display of short tandem repeats based on signal decomposition. AB - This paper presents a wavelet-based Empirical Mode Decomposition (EMD) to detect short tandem repeats in DNA sequences. A wavelet subspace algorithm combined with EMD is introduced as a pre-processor and a Cross-Correlation Analysis (CCA) is applied as a post-processor to create subspaced Intrinsic Mode Functions (IMFs). The new proposed method is called the Empirical Mode and Wavelet Decomposition (EMWD). The algorithms can display the power spectral density in the two dimensional frequency-time (f-t) plane efficiently for both very long signals and short signals. Simulations are applied on the real human DNA sequences from public data source Genbank (http://www.ncbi.nlm.nih.gov/Genbank/). Application of the EMWD algorithms to the short tandem repeat detection has achieved an averaged accuracy of 98.5%. PMID- 22295751 TI - Predicting functional residues of protein sequence alignments as a feature selection task. AB - Determining which residues within a multiple alignment of protein sequences are most responsible for protein function is a difficult and important task in bioinformatics. Here, we show that this task is an application of the standard Feature Selection (FS) problem. We show the comparison of standard FS techniques with more specialised algorithms on a range of data sets backed by experimental evidence, and find that some standard algorithms perform as well as specialised ones. We also discuss how considering the discriminating power of combinations of residue positions, rather than the power of each position individually, has the potential to improve the performance of such algorithms. PMID- 22295752 TI - A novel statistical algorithm for enhancing the utility of HapMap data to design genomic association studies in non-HapMap populations. AB - The HapMap database should be effectively used in designing disease association studies in non-HapMap populations. The efficiency of portability of tagSNPs from HapMap to non-HapMap populations is widely variable. A new algorithm is proposed for selecting SNPs from HapMap for use in non-HapMap populations by simultaneously considering and combining data on allele frequencies and linkage disequilibrium values in the four HapMap populations. Empirical comparison and validation of the algorithm are provided by using Tagger, available HapMap data and data from an Indian population. The proposed method is shown to be efficient and effective. A software implementing this algorithm is freely available. PMID- 22295753 TI - [Preparation of core-shell magnetic nanoparticles and its application in separation and spectral detection]. AB - Magnetic nanoparticles as well as core-shell magnetic nanocomposites are of great interest for researchers due to their potential applications in lots of areas. In the present review, the authors summarized several universal synthetic methods of nanocomposites and their specific properties. In the following, the authors focused on the applications of functionalized magnetic nanoparticles in separation and spectral detection, along with the introduction of some work in the authors' lab. At last, the questions remaining in magnetic nanoparticles and the application perspectives of magnetic nanocomposites were discussed. PMID- 22295754 TI - The improvement of bulk-heterojunction order in polymer photovoltaic device. AB - The blend morphology and vertical arrangement are critical to the performance of organic bulk-heterojunction photovoltaic devices. In the present paper, the authors proposed a new annealing method that controls the blend morphology and vertical arrangement of two materials by means of simultaneously applying external electrical field and violet irradiation on the active layer of poly(3 hexylthiophene) (P3HT) and [6,6]-phenyl C61-butyric acid methyl ester (PCBM) during annealing process. By using this annealing method, the power conversion efficiency increased by 36%, which was caused by vertical phased-separated blend of crystalline P3HT and PCBM and better charge extraction of electrodes. X-ray photoelectron spectroscopy (XPS) was measured to prove more fullerene derivatives at the organic/cathode interfaces by using this annealing method. The X-ray diffraction (XRD) analysis and UV-Vis absorption spectrum analysis also revealed more ordered polymer crystallization. PMID- 22295755 TI - [Study of CH4 spectroscopy at low temperature near 1.65 microm]. AB - In the CH4 absorption spectroscopy measurement, especially the measurements at low temperature, the accurate values of the absorption spectral parameters are very important. The absorption spectral parameters are especially important when the authors use parameters to sense and model the atmospheres of the earth and the outer planets. Sometimes the CH4 parameters listed in the HITRAN 2008 database are uncertain to some extent. In order to measure the low temperature absorption spectroscopy of methane, the authors used a cryogenic cell newly developed by ourselves in combination with a distributed feedback (DFB) diode laser as the light source and measured the low stated energy and the rotational angular momentum. And while the authors compared our data with HITRAN 2008, the authors modeled the line intensity changing with the temperature. The authors' measured parameters will be helpful for sensing and modelling the atmospheres of the earth and the outer planets. PMID- 22295756 TI - [The influence of laser plasma effects on the characteristics of silicon surface damage]. AB - Silicon is the basic material for electro-photonic detectors, so the studies of the laser induced damage of silicon are of great significance in laser detecting and military applications. The damage characters of silicon under high intensity nanosecond laser pulses were investigated in the present paper. The results show that laser plasma has thermal effect, shock effect and spectral radiation effect, etc. These comprehensive effects combined together determinate the damage characters. By thermal effects and shock effects of laser plasma, the material is being melt, vaporized, ionized and pushed out at the laser irradiated area. In this way, the pit can be formed and the cooled ejected effluents are radially distributed. The silicon was melt at the bottom of the pit and the temperature was modulated by the intensity of the incident laser, which interfered with scattering laser simultaneously. The periodic heat distribution generates the period stripes. N, O and Si characteristic spectrum in the laser plasma prove that the colored film is the mixture of SiOx:SiNy which were sprayed out from laser plasma under repetitive laser pulses. PMID- 22295757 TI - [Preparation and luminescent performance of Tb3+ doped SiO2 core-shell nanoparticles]. AB - The authors synthesized the core-shell nanoparticles of SiO2-coated SiO2:Tb3+ by using sol-gel method (SiO2:Tb3+ @SiO2), and studied the influence of core-shell ratio and preparation craftwork on its luminescence properties. The photograph of TEM and EDS showed that SiO2:Tb3+ were coated successfully by SiO2. The authors found that the samples of SiO2:Tb3+ @SiO2 prepared by mixing of core and shell after shell aging with the ratio of core/shell being 1.2 g/25 mL had the stronger fluorescence intensity. Time-resolved spectra showed that the SiO2:Tb3+ @SiO2 had longer fluorescence life time than SiO2:Tb3+. PMID- 22295758 TI - [Progress in study of biomacromolecular damages by infrared spectroscopy]. AB - Infrared spectroscopy (IR) is employed as an important tool in the investigation of biological macromolecules because of its high sensitivity and nondestructivity to samples. When proteins, lipids or nucleic acids are damaged, the position, shape and intensity of their IR characteristic absorption peaks will be significantly changed. This provides evidences for the determination of the damages of biomolecules, which further shed light on the clarification of the occurrence, development and early prevention of some diseases. In the present paper, the applications of IR to the detection of biomolecular damages are reviewed. Various IR techniques are introduced, including Fourier transform infrared spectroscopy (FTIR), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), Fourier transform infrared spectroscopy microscope and so on. A general review was performed for the application of IR technique to the qualitative and quantitative analysis of secondary structure of protein, fluidity of membrane lipid, interaction of drugs with DNA and so on. The existing problems of IR were pointed out and the prospect of IR technique in the field of biomedicine was discussed. It is expected that, in the future the researches involving IR techniques will be focused on the application in early diagnosis of diseases, instrumental combinations and quantitative techniques. PMID- 22295759 TI - [Review of crop residue fractional cover monitoring with remote sensing]. AB - Crop residue, as an important element of agro-ecosystem, can influence the flow of nutrients, carbon, water, and energy in agro-ecosystem. As a crucial indicator of distribution of crop residue, crop residue fractional cover is a key parameter of agro-ecosystem carbon cycle process model. Since remote sensing can easily obtain quantities of data, many researches were carried out on monitoring crop residue fractional cover with remote sensing. The present paper summarizes crop residue fractional cover estimation methods and latest progress in remote sensing, and these methods are classified into five categories according to the differences in methodologies and data sources. The principle of every method is described and compared. The advantages and shortages are also discussed and analyzed. Eventually, this paper points out some methods that should be improved, and presents the prospects of crop residue fractional cover estimation in the future. PMID- 22295760 TI - [Terahertz time-domain spectroscopy of Clenbuterol hydrochloride]. AB - The terahertz spectra of Clenbuterol hydrochloride in the range of 0.2 to 2.6 THz were obtained by THz time-domain spectroscopy, the absorption and refraction spectra of Clenbuterol hydrochloride was got meanwhile. The structure and vibrational frequencies of Clenbuterol molecule, Clenbuterol hydrochloride molecule and Clenbuterol hydrochloride crystal in the THz range were simulated. Based on the difference between experimental and theoretical results, the origin of the vibrational frequencies was analyzed. This study demonstrated the feasibility of time-domain terahertz spectroscopy for the identification of Clenbuterol hydrochloride and provides a new way for the detection of Clenbuterol hydrochloride. PMID- 22295761 TI - [Study on spatial distribution of electron energy in hollowneedle-plate dielectric barrier discharge]. AB - In the present work, the spatial distributions of spectrum intensity of molecule and atom in the plasma generated in hollowneedle-plate discharge in atmosphere were measured, and the spatial distribution of electron energy in plasma was analyzed. A plasma about 3 cm long is generated by using a hollowneedle-plate discharge device. By collecting optical emission spectrum from 300 to 800 nm, it was found that the spectrum consists of strong Ar I lines, strong second positive band system of N2, and weak OI line. The spatial distributions of spectrum intensity of Ar I (696.54, 763.51, 772.42, and 794.82 nm), band N2 (337.1, 357.6, and 380.4 nm), and OI 777.2 nm were measured. The Ar I lines decreased gradually from the arc root. The N2 lines increased gradually from the arc root and declined when they reached a maximum at 12 mm away from the arc root. The intensity of OI increased from the arc root and declined when it reached a maximum at 6 mm away from the arc root. The spatial distribution of electron energy in plasma was analyzed qualitatively from the spatial distribution of spectrum intensity given above. It was found that the electrons located at 6 mm away from the are root have high energy, while they have low energy at arc tip. PMID- 22295762 TI - [Spectroscopic properties of Pr3+ doped transparent oxyfluoride vitroceramics]. AB - In the present paper, the room-temperature absorption spectrum of Pr+ -doped transparent oxyfluoride vitroceramics (Pr(0.2):FOV) was studied systematically. The optical characterisation of Pr(0.2):FOV was performed. The standard and modified Judd-Ofelt theories were used to determine the J-O intensity parameters. The problems with standard Judd-Ofelt theorie for Pr3+ were discussed. Based on the intensity parameters, some predicted optical parameters, such as the spontaneous radiative transition probabilities, radiative lifetimes, branching ratios and integrated emission cross section were calculated. And the application of Pr:FOV was analyzed. Especially there are large oscillator strength and large integrated emission cross section in the transitions of (3)P0-->(3)H4, (3)P1- >(3)H5 and (3)P0-->(3)H6, (3)P0-->(3)F2. So, they are more worthy of attention. The obtained spectroscopic results show the potential application of the Pr3+ doped oxyfluoride vitroceramics for solid-state lasers. PMID- 22295763 TI - [Synthesis and luminescence properties of Y10W2O21:Eu nanophosphor]. AB - In the present paper, a novel nanophosphor, Y10W2O21:Eu was synthesized through a simple and low-cost method: co-precipitation. The results of XRD show that resultant samples are Orthorhombic phase and primitive lattice. The average crystallographic sizes could be confirmed to be approximately 80 nm by means of the Scherrer formula, which are in good agreement with the particles sizes exhibited by SEM. In the excitation spectra of Y10W2O21:Eu nanophosphor, by monitoring 610 nm, the charge transfer bands (CTB) of O--Eu and O--W, centering at around 270 and 307 nm, can be observed, respectively. The spectral lines shape and locations of excitation peak corresponding to 4f-->4f transitions are similar in all samples. But the relative intensity ratios between O--Eu and O--W CTB excitation peak increase with the Eu3+ doping concentration increasing. The characteristic red emission at around 610 nm of Eu3+ was also observed, ascribed to the (5)D0--(7)>F2 transition of Eu3+, and the optimal doping concentration is 20 mol%. Finally, the transition intensity parameters omega(lamda = 2,4) and the quantum efficiencies of (5)D0 level of Eu3+ were calculated according to Judd Ofelt theory. The results indicate that Eu(3+5)D0-->(7)F2 610 nm red luminescence can be effectively excited by 394 nm near-UV light and 464 nm blue light in Y10W2O21 host, which is similar to the familiar Eu3+ doped tungstate (e.g., Gd2(WO4)3, CaWO4). Therefore, the Y10W2O21:Eu red nanophosphors may have a potential application for white LED. PMID- 22295764 TI - [Thermoluminescence study on Sr2SiO4 long afterglow material doped with Eu2+]. AB - Sr2SiO4:Eu0.03(2+) phosphors were synthesized through the solid-state reaction technique. The X-ray diffraction shows that the phase of the phosphors is orthorhombic alpha'-Sr2SiO4. The produced phosphors show one intense emission band located at 490 nm. The phosphor shows a long afterglow properties excited by the sunlight. The decay characteristics show that the phosphors consist of a quick decay process and a slow decay process. The experimental results demonstrate that the thermoluminescence (TL) curves of the samples containing four peaks, located at 346, 420, 457 and 552 K, respectively. Meanwhile, the different peaks show the different decay characteristics, and the electron transfer between the trap levels was measured. PMID- 22295765 TI - [Study on building MLR model using orthogonal signal correction]. AB - MLR and PLS models with or without OSC were studied through establishing quantitative calibration models for the peanut oil content in blending edible oils, and for the dimethylsulfoxide concentration in water solution. The cross validation results and the predication results of MLR models, were compared to evaluate the effectiveness of OSC for improving the performance of MLR model. The results show that the SEC or SEP of MLR models using OSC gets smaller. Selecting appropriate wavelengths combination by CARS method, prediction capacity of MLR model using OSC is better than PLS1 model using raw spectrum. PMID- 22295766 TI - [Research on VOC concentration detection by photoelastic modulation infrared spectrum absorption method]. AB - In order to ensure high stability and strong anti-interference ability in static interference system for qualitative and quantitative analysis of gas, a static scans interference detection system was designed based on photoelastic modulation infrared spectrum absorption system. The system consists of infrared laser, polarizer, photoelastic modulator, polarization analyzer and CCD components. By photoelastic modulator the principal refractive index of optical crystal will change cyclically by the modulation signal, producing cyclical changes in the optical path difference. With the calculation of modulation phase variation, the authors can get the function of the crystal length, the modulation cycle, and the range of optical path difference. Based on phase delay value and the energy distribution of interference pattern, the authors got the formula for the corresponding interference light intensity. The experiment used ZnSe crystal as the photoelastic modulation crystal, the polarizer uses the DOP3212 polarizer, and the detector uses the TCD5390AP array CCD. The five groups have different concentrations with three common VOC gases (formaldehyde, benzene and xylene) for detecting the concentrations of gases. The experimental results with the traditional infrared absorption were compared with the test results of photoelastic modulation infrared spectrum absorption method. The method of photoelastic modulation infrared spectrum absorption had high stability and real time features, while the detection accuracy is better than the traditional infrared absorption method. PMID- 22295767 TI - [Research on high-precision temperature measurement system based on near infrared spectroscopy]. AB - At present, the interference from outside radiation under the complex environment is difficult to eliminate by using the infrared thermometry method. It leads to the low measurement accuracy. In the present paper, a high-precision infrared temperature measurement system was designed. The light filter method is presented in this system. The broadband filters and three-level interference filter were combined in this method. According to the method, the near-infrared spectra sent out by high temperature object is filtered. The high temperature background light and the environment obtrusive light are filtered out. In this way, two monochromatic spectra are obtained. The radiation power ratio is received after receiving by the infrared detector. Then the temperature is obtained by calculating. In this system, the bandwidth of monochromatic spectrum permeated is only 1 nm. The inhibition of radiation from background light and ambient light except transmittance spectrum is up to 8 orders of magnitude. The measurement error caused by the ambient temperature heating of the measured object is reduced. The accuracy of the temperature measurement system is improved. Finally, the temperature measurement system is feasible according to the experiment result. The precision reached to 0.2%. PMID- 22295768 TI - [Study on rapid determination of nutrient composition in corn distillers dried grains with solubles by near-infrared reflectance spectroscopy]. AB - The possibility of using near-infrared reflectance spectroscopy (NIRS) for quantitative determination of 8 important nutrient compositions, including moisture, crude protein, ether extract, ash, total phosphorus, neutral detergent fiber, acid detergent fiber and crude fiber in corn DDGS was investigated in the present study. Ninety-three samples were collected from 18 plants in China over a three years period. Calibrations were performed by modified partial least squared algorithm and 15 different derivatives plus scatter correction spectral pretreatments. The results showed that the second derivative mathematical treatment gave the best prediction performance for most constituents. The prediction performance of models developed using 93 calibration samples was better than that developed using 70 samples. The coefficients of determination for calibration (RSQcal), coefficients of determination for cross-validation (1 VR), and RPD(CV) of cross-validation in models developed using 93 samples were 0.94-0.99, 0.89-0.99, and 2.98-14.85, respectively. These results indicate that NIRS can be used as a quantitative method for rapid determination of nutrient composition in corn DDGS. PMID- 22295769 TI - [Study of soil organic carbon structural change of fallowing grasslands by synchrotron radiation spectrum technology]. AB - Synchrotron radiation soft X-ray and SR-FTIR spectroscopy technique were used to study the change of soil organic carbon (SOC) structure in < 0.25 mm aggregate soil from fallowing grasslands of Yun-wu mountains. Results obtained by SR-FTIR technique were qualitatively analyzed, which indicated that compared with slope farmland, the peak intensity of aliphatic-C from fallowing grasslands significantly increased, while peaks intensity of aromatic-C, alcohols-C, carboxyl-C, polysaccharide-C didn't significantly change with increasing years of fallowing. Results obtained by SR-FTIR technique were semiquantitatively analyzed, which showed that compared with slope farmland, the relative content of functional groups from fallowing grasslands SOC was increased, the growing rate of aliphatic-C, alcohols-C in 0-5 cm and 10-20 cm soil horizon was greater than growing rate of aromatic-C. Results obtained by soft X-ray technique are consistent with SR-FTIR, and the relative content of the same functional groups (aliphatic-C, aromatic-C) gained by two determination methods were T-tested, which was not significant (P > 0.05), indicating that using synchrotron radiation soft X-ray for the determination of SOC structural change of fallowing grass lands is feasible. PMID- 22295770 TI - [Application of NIR spectroscopy to estimate of MFA and fiber length of Neosinocalamus a f finis]. AB - Near infrared spectroscopy was applied to rapidly predict microfibril angle (MFA) and fiber length of Neosinocalamus a f finis Keng by using a fiber-optic probe in diffuse reflectance mode. The MFA and fiber length were measured by X-ray diffractometry and optical microscope, respectively. Partial least squares (PLS) was used to build models based on raw and pretreated spectra, including noise spectra and noise combined with orthogonal signal correction (OSC) spectra. The results showed that the PLS models of MFA and fiber length, based on noise combined with OSC spectra, gave the strongest correlations, with correlation coefficient (R) of 0.8936 and 0.9883 and root mean standard error of prediction (RMSEP) of 0.2920 and 0.1460 in prediction set. The correlations between NIR predicted and MFA/fiber length actual values are very good. Therefore, it is concluded that MFA and fiber length of N. a f finis can be estimated by NIR spectroscopy with sufficient accuracy. PMID- 22295771 TI - [Monitoring and analysis of urban ozone using open path Fourier transform infrared spectrometry]. AB - An ozone monitoring system was developed by the method of open path Fourier transform infrared (OP-FTIR) spectrometry based on our FTIR spectrometer. In order to improve measurement precision and detection limit, the quantitative analysis was completed to get ozone concentration by combining synthetic background spectrum method which uses information from HITRAN database and instrumental line shape, and nonlinear least squares (NLLSQ) method. The measurement methods for system detection limit were discussed and the result is 1.42 nmol x mol(-1) with sixteen times averages. The authors developed continuous monitoring experiments in the suburban area of Hefei. For the day and month measurement results, the authors analyzed their variations with the generation sources. The result has shown that this system is reliable and precise and can be used as a new device and method for national ozone monitoring. PMID- 22295772 TI - [Detection of benzoyl peroxide in wheat flour by NIR diffuse reflectance spectroscopy technique]. AB - Adding benzoyl peroxide (BPO) into wheat flour was prohibited by the relevant government departments since May 1, 2011. And it is of great importance to detect BPO additive amount in wheat flour quickly and accurately. Part of BPO which was added into wheat flour will be deoxidized into benzoic acid, and this make it complex to detect the original BPO additive amount. The objective of the present research is to investigate the potential of NIR diffuse reflectance spectroscopy as a way for measurement of BPO original adding amount in wheat flour. A total of 133 wheat flour samples were prepared by adding different content of BPO into pure wheat flour. Spectra data were obtained by NIR spectrometer and then denoised by wavelet transform. Ninety seven samples were taken as calibration set and other 36 samples as prediction set. Partial least squares regression (PLSR) was applied to establish the calibration model between BPO original adding contents and the spectra data. The determination coefficient of model for the calibration set is 0.8901, and root mean squared error of calibration (RMSEC) is 40.85 mg x kg(-1). The determination coefficient for the prediction set is 0.8865, and root mean squared error of prediction (RMSEP) is 44.69 mg x kg(-1). The result indicates that it is feasible to detect the BPO adding contents in wheat flour by NIR diffuse reflectance spectroscopy technique and this technique has the potential to measure some other additives in food. PMID- 22295773 TI - [Rapid diagnostics of early phosphorus deficiency in mini-cucumber plants under protected cultivation by near infrared spectroscopy]. AB - The morphological symptom of phosphorus deficiency at early stage is similar to the appearance of leaf aging process in preliminary phase, so that visual diagnostics of phosphorus deficiency in mini-cucumber plants at early stage is practically impossible. Near infrared reflectance spectra contain information about differences in compositions of leaf tissues between phosphorus-deficient plants and healthy plants. In the present paper, near infrared reflectance spectroscopy was used to provide diagnostic information on phosphorus deficiency of mini-cucumber plants grown under non-soil conditions. Near infrared spectra was collected from 90 leaves of mini-cucumber plants. Raw cucumber spectra was preprocessed by SNV and divided into 27 intervals. The top 10 principal components (PCs) were extracted as the input of BP-ANN classifiers by principal component analysis (PCA) while the values of nutrient deficient were used as the output variables of BP-ANN and three layers BP-ANN discrimination model was built. The best experiment results were based on the top 3 principal components of No. 7 interval when the spectra was divided into 27 intervals and identification rates of the ANN model are 100% in both training set and the prediction set. The overall results show that NIR spectroscopy combined with BP ANN can be efficiently utilized for rapid and early diagnostics of phosphorus deficiency in mini-cucumber plants. PMID- 22295774 TI - [Study on recognition of the true or false red wine based on visible-near infrared spectroscopy]. AB - This study selected 90 samples from different brands of red wine. In order to eliminate the impact of spectral curve's baseline, the first derivatives of all of spectral curves were calculated and the principal component analysis was carried out on the first derivative spectra. The result showed that the contribution rate of the first two principal components was over 80 percent. By the first two principal components, all the red wine samples were obviously divided into two classes. Furthermore a 3-layer artificial neural network predictive model was built with the first four principal components as input variables and 100 percent correct prediction rate was gained. The research showed that the visible-near infrared spectroscopy combined with principal component analysis provides an accurate and reliable new method to rapidly and nondestructively recognize the true or false red wines. PMID- 22295775 TI - [Thymine on silver island films: surface-enhanced Raman scattering and surface enhanced infrared absorption studies]. AB - Thymine, being one of the four nucleobases in the nucleic acid of DNA, has received an increasing interest due to its potential importance in genetics and possible applications in medical science. In the present study, adsorption of thymine on laser-ablated silver island films was comparatively analyzed by means of surface-enhanced Raman scattering (SERS) and surface-enhanced infrared absorption (SEIRA). Two new bands at 1305 and 1573 cm(-1) appeared in the SERS spectrum of thymine on silver island films and represented that the molecule configuration of thymine hydrolyzed ion compound changed its structure from a keto form to an enol one. The greater enhancements of in-plane ring breath vibration bands and of 1649 cm(-1) band associated with C(4)==O stretching vibration clearly suggested that the thymine molecules were adsorbed on the silver surface via O(8). The interaction of N(3) with silver surface could be inferred by the emergence of a stronger peak at 773 cm(-1), which was assigned to the ring breath caused by the stretching vibration of the C(6)--N(3)--C(2). The blue shift of ring breath vibration from 749 to 773 cm(-1) indicated that thymine ring should have some weak interaction with silver surface, i.e., there was a certain angle between the thymine ring and the silver surface. To sum up, the SERS spectrum indicated that thymine adsorbed on the silver surface as enolate through the O(8) and N(3) atoms. The molecular plane assumed a tilted orientation with respect to the silver surface. Laser-ablated silver island films also exhibited a good surface enhancement to infrared absorption for thymine. Enhancement factor was estimated to be about 200 under our experimental condition. There was no shift of C(2)==O stretching vibration in SEIRA spectrum, revealing that O(7) was not involved in the adsorption process. Consistent with our SERS spectrum, the greater enhancement of the thymine ring deformation vibration (1730 cm(-1)) in SEIRA agreed a tilted orientation of thymine on silver surface. PMID- 22295776 TI - [The study of several aldehyde molecules by Raman spectroscopy]. AB - The Raman spectra of formaldehyde, acetaldehyde, propionaldehyde and n butyraladehyde (CnH2nO,n = 1, 2, 3, 4) were obtained by portable Raman spectrometer. The molecules of the four aldehydes were calculated by density functional theory (DFT). By comparing the calculated result and the experimental result, the bands of these Raman spectra were assigned. And the Raman spectra of these aldehydes molecules were analyzed and compared. These aldehydes could be real-time rapidly identified by Raman spectroscopy technology. PMID- 22295777 TI - [Spectrum diagnosis of enhanced arcjet thruster using hydrazine propellant]. AB - A set of spectrum diagnostic system was established. With this system, spectrum analysis was carried out for the plume signal of enhanced arcjet thrust using catalytic decomposition products of hydrazine as propellant. Excitation plume temperatures for various wavelengths were obtained through measuring spectral radiation intensity. The averaged excitation temperatures were analyzed based on Boltzman diagram. The results show that there is the highest temperature in the axial center of plume and the temperature drops quickly in the radial direction. The intensity of thermodynamic non-equilibrium weakens with a decrease in current and an increase in radial distance. The temperature of the plume rises with an increase in the proportion of ammonia in the catalytic decomposition mixture of hydrazine. PMID- 22295778 TI - [Study on the automatic extraction method of spectral data features in laser induced breakdown spectroscopy]. AB - According to that the spectral line broadening of laser induced breakdown spectroscopy (LIBS) was lorentz nonlinear function model, using Levenberg Marquardt (L-M) agorithm to optimally estimate the undetermined parameter in the function, the continuum background radiation and peak position and peak intensity were corrected, and the method of data points automatic extraction for fitting was analysed. Automatic fitting and feature parameter extraction for spectral data of LIBS based on L-M algorithm that was hybrid programming with matrixVB and VB were accomplished,and the result was compared with the origin 7.5 data analysis software which was manual and commonly used and verified its stability and reliability. PMID- 22295779 TI - [Quantitative analysis of slag by calibration-free laser-induced breakdown spectroscopy]. AB - Calibration-free laser induced breakdown spectroscopy (CF-LIBS) was employed for the quantitative analysis of slag. Nd:YAG laser ablation was performed in air. The laser-induced plasma emission was measured by an Echelle spectrometer equipped with an ICCD. The plasma temperature and electron number density were determined from Boltzmann plots and a Ca I line width, respectively. The assumption of local thermal equilibrium was validated by the Ne criterion. The concentration of oxides was obtained from the concentration of elements by using stoichiometric relation. The calculated oxide concentrations were compared with those obtained by XRF. The relative errors of major elements were less than 15%. The results indicate that this method can be employed for the analysis of major elements in multi-component complex materials without certified reference. PMID- 22295780 TI - [Observation and diagnostic of ultraviolet spectra in the solar transition region]. AB - The solar transition region is the thin atmosphere layer between the chromosphere and corona. Although the thickness of the solar transition region is only several hundred kilometers, the parameters of the plasma change dramatically. The temperature increases from 10(4) to 10(6) K and the density drops from 10(10) to 10(8) cm(-3). The emission of the solar transition region is generally of optical thin far-ultraviolet (FUV) spectral lines, extreme-ultraviolet (EUV) spectral lines and background continuous spectral lines. However, the traditional ground based observations can not be made for FUV/EUV lines, owing to their strong absorption by ozone and other molecules in the earth's atmosphere. Thus, FUV/EUV lines only can be obtained with space-based observations. In recent decades, the successful launch of space-borne instruments opened a new era of the research for the solar transition region. The present paper reviews the observation history of ultraviolet spectra in the solar transition region and some kinds of space-borne instruments, especially several important spectrometers in recent ten years. At the same time, the diagnostics of the emissivity, electron density and electronic temperature of ultraviolet spectra in the solar transition region are expounded in detail. The shape of ultraviolet line is discussed and several important parameters with physical significance are showed using SOHO/SUMER spectrometer. PMID- 22295781 TI - [Hydrothermal synthesis, crystal structure and luminescence property of 3D supermolecular compound [Zn(H2O)6].(C16H8O8)]. AB - A supermolecular compound [Zn(H2O)6].(C16H8O8) was synthesized with 3,3', 4,4' bipthenyltetracarboxylic acid (H4BPTC) and Zn(CH3COO)2.2H2O. Its structure was determined by single crystal X-ray diffraction, IR and element analysis. The crystal belongs to triclinic system with space group and the cell parameters are: a = 0.65484 (13) nm, b = 0.79388 (16) nm, c = 0.96812 (19) nm, alpha = 76.29 (3) degrees, beta = 87.75 (3) degrees, gamma = 86.43 (3) degrees, Z=1, R1 = 0.0665, wR2 = 0.1833, and GOF = 1.021. We have studied the luminescence property of compound 1, The compound 1 has blue-purple luminescence in solutions of DMSO and green luminescence in the solid state at room temperature. In the solid state, the emission frequencies for complex 1 are red-shifted compared with their emission maximum peaks in solutions of DMSO. This red-shift of emission energy from solution to solid is likely to be caused by the intermolecular interaction in the solid state that effectively decreases the energy gap. PMID- 22295782 TI - [Fluorescence fingerprint transformation of municipal wastewater caused by aerobic treatment]. AB - The conventional parameters such as COD and BOD only could represent information about total organic content. Fluorescence spectrum can display organic composition and it is unique for each sample, so it is referred as "fluorescence fingerprint". In the present study transformation of excitation-emission matrix of municipal wastewater with sewage as major components after aerobic treatment was investigated and then the zones of biodegradable and non-biodegradable organic matters were figured out: the fluorescence at excitation wavelength/emission wavelength of about 280/340 nm and 225/240 nm derived from biodegradable organics and those of the zone of excitation wavelength above 300 nm and the zone of excitation wavelength below 300 nm and emission wavelength above 400 nm were mainly related with non-biodegradable organics. The above mentioned results indicated that fluorescence fingerprint could be used to evaluate the performance and instruct design and operation of aerobic systems. PMID- 22295783 TI - [Fluorescence spectra analysis of whey protein isolate-dextran conjugate]. AB - The mixed whey protein isolate (WPI)-dextran was treated by dry-heating to prepare Maillard reaction products (MRPs), which was characterized by the browning. The free amino groups content significantly decreased by 35.77% and 30.53% in glycated protein samples, as the molecular weight of dextran increased from 67 to 150 kD, respectively. This suggested that it was more difficult to be linked with WPI molecule when the chain length of dextran was increased. The characteristic of WPI-dextran conjugate was studied by fluorescence spectra in the paper. The maximum fluorescence intensity at 405 nm was obviously enhanced and G67 showed high fluorescence intensity than G150 over the wavelength range form 350 to 500 nm. This result revealed that the flourescent substance, a feature in Maillard reaction model system, was generated. As showed in the fluorescence spectra, the maximum fluorescence intensity at 470 nm was significantly decreased and the fluorescence intensity in each solution was in the order as follows: WPI>G150>G67. Moreover, the measurement of surface hydrophobicity index further showed that the hydrophobicity of WPI could be suppressed due to these two kinds of different molecular weight dextran. PMID- 22295784 TI - [Study of photoluminesence property of CdS/PAMAM nanocomposites]. AB - The photoluminescence property of CdS/PAMAM nanocomposites in water at different ratio of Cd2+ to PAMAM(r) was studied by fluorescence emission spectrum, and the according mechanism was explored. The results indicate that in the irradiation of UV light at the wavelength of 330 nm, two peaks were shown in the fluorescence emission spectrum of CdS/PAMAM nanocomposites. One peak was attributed to PAMAM dendrimers, and the another came from CdS QDs. The strength of the frontier fluorescence emission peak became weaker and weaker, and at last disappeared with the enhancement of the ratio of Cd2+ to PAMAM; the strength of the latter fluorescence emission peak became stronger, which indicates that the electron at valence band of N atom in amines of dendrimers was transferred to CdS QDs. Oil latent finger marks deposited on transparent adhesive tapes surface treated with pure PAMAM solution with blue photoluminescence was not clear enough because of the blue light emitted from the impurity in adhesive tapes; Latent finger marks emitted strong yellow light and were successfully detected with good resolving rate with CdS/dendrimer solution with r of 10, which shows good reference value for detecting finger marks on surfaces with impurities emitting different photoluminescence colors. PMID- 22295785 TI - [Synthesis and spectra characterization of nano-sized Ce(1-x)(Fe(0.5)La(0.5))xO(2 delta) solid solutions]. AB - Ce(1-x)(Fe(0.5)La(0.5))xO(2-delta) solid solutions were obtained via hydrothermal method. The structure of the solid solutions and the cell parameters were characterized by XRD analysis technique, the electron transition properties and doping effectswere measured by UV-Vis diffraction spectrum and Raman spectrum technique. XRD results showed that Ce(1-x)(Fe(0.5)La(0.5))xO(2-delta) id solutions exhibited cubic fluorite structure till the doping content increased to 0.30. Tiny Fe2O3 phase was observed when x = 0.30. The particle size was kept nanoscaled, and location of different kind of doping ions in CeO2 lattice was discussed. By increasing the doping content, the cell parameter was kept increasing gradually till x = 0.18, then it remained almost constant. The UV-Vis diffraction spectrum analysis showed that the absorption threshold edge redshifted, the band gap energy decreased with increasing the doping content. The valence of Fe ions in the lattice of CeO2 was +3. The F2g Raman mode also showed a downshift, and the peak gradually became broader, which further proved the influence of the dopant. PMID- 22295786 TI - [Effect of S-configuration transformation on the microstructure of ovalbumin]. AB - The effect of S-configuration transformation on the microstructure of ovalbumin was studied by CD spectra, XRD spectra, ANS fluorescence probe emission spectra and UV absorption spectra. CD spectra was used to examine the changes in the secondary structure of the ovalbumin during S-ovalbumin information process. When the induction time was prolonged, the mutual transformation between alpha-helix, beta-sheet, beta-turn and the random coil was observed, and the orderliness of the secondary structure was increased with alpha-helix decreasing slightly and beta-sheet increasing correspondingly. XRD spectra analysis showed that the crystal structure content of the ovalbumin increased with prolonging the induction time and the largest data was observed at 72 h, indicating that the orderliness of the secondary structure was increased. The results were similar to CD spectra analysis. The ANS fluorescence probe emission spectra analysis demonstrated that S-configuration transformation induced an increase in surface hydrophobicity with prolonging the induction time, and the largest data was also observed at 72 h. In addition, UV absorption spectra analysis indicated that S configuration transformation resulted in a decrease in the UV-absorption maximum value with prolonging the induction time, indicating that the aromatic amino acid was buried in the molecular interior. The results indicated that the changes in the microstructure of ovalbumin were relevant to S-configuration transformation. PMID- 22295787 TI - [Spectroscopic study of photocatalytic mechanism of methanol and CO2]. AB - Ni-Ti-O/SiO2 catalyst was prepared by impregnation method, and its photocatalytic performance for carbonylation of methanol with CO2 was investigated under UV light. The in-situ IR, XPS and MS were carried out to analyze the possible photocatalytic reaction mechanism. Results indicated that the Ni-Ti-O/SiO2 exhibited good photocatalytic performance for carbonylation of methanol with CO2, the methanol conversion reached up to 24.9%, and the selectivity for the carbonylated products was more than 60% within 180 min reaction time. The catalyst characterization results showed that the O==C .--O- and CH3OC(O)* might be important intermediate in the carbonylation of methanol with CO2. PMID- 22295788 TI - [Identification of invoice based on laser-induced photoluminescence spectrum]. AB - The rapid identification of invoice authenticity was studied based on laser induced photoluminescence spectrum. First, the spectral curves of eighty invoice samples were obtained by laser-induced photoluminescence detection system, and genetic algorithm (GA) was applied to fit and separate overlapped spectral region between 566 and 669 nm by three Gaussian peaks. Spectral feature parameters extracted by GA were employed as the inputs of BP neural networks, and then an identification model was built. One hundred and four data were converted to 13 Gaussian parameters, and for authentic and false invoices the coefficients of determination (R2) were 0.99789 and 0.99683 and the relative standard deviations (RSD) were 0.017052 and 0.022362, respectively. It was showed that Gaussian fitting algorithm could not only simplify the parameters of models, but also improve the explanation of analysis models. Through comparison analysis of the results, it was found that the model, whose thirteen feature parameters and two evaluated parameters were all applied as BP inputs, was the best, and the corrected identification rates of sixty calibration samples and twenty validation samples were both 100%. So the identification method studied in the present research played a good role in the classification and identification, and offered a new approach to the rapid identification of invoice authenticity. PMID- 22295789 TI - [Research on detecting trace formaldehyde gas by the multi-wavelengths characteristics method]. AB - In order to overcome the slow speed of detecting trace formaldehyde in the sample gas, material consumption by chemical reaction, and the limitations of the sampling area in the detection of trace formaldehyde, a multi-wavelength characteristics method for getting the exact concentration of formaldehyde quickly was designed. According to the spectrum characteristics of formaldehyde and the main interfering gases the system chose multiple wavelengths with the minimum degree of coherence (the number of characteristic wavelengths were selected to be 3, 4 and 5), in conjunction with the corresponding groups of narrow-band filters. With the infrared light of the light source through the chamber windows and narrow-band filters, the infrared light was collected by the PCI-2TE-13 infrared detectors, and the concentration of formaldehyde in the sample gas was calculated by the characteristics spectrum absorption algorithm. In the experiments, the system analyzed and calculated the concentration of formaldehyde in four gas samples collected in the newly renovated house, building materials market, supermarkets and outdoor parks. Experimental results of the system and test results of ARCSpectro-AMIR infrared spectrometer were compared, the results show that test data above 10 mg x m(-3) were close to true value by the multi-wavelengths characteristics method, and the average error is less than 5%. So the system meets the requirements of practical applications, and it has the advantages of real-time detection, not poisoning so on. PMID- 22295790 TI - [Response characteristics of the field-measured spectrum for the four general types of halophyte and species recognition in the northern slope area of Tianshan Mountain in Xinjiang]. AB - Based on the field-measured Vis-NIR reflectance of four common types of halophyte (Achnatherum splendens(Trin.) Nevski, Sophora alopecuroides L., Camphorosma monspeliaca L. subsp. lessingii(L.)Aellen, Alhagi sparsifolia shap) within given spots in the Northern Slope Area of Tianshan Mountain in Xinjiang, the spectral response characteristics and species recognition of these types of halophyte were analyzed. The results showed that (Alhagi sparsifolia shap) had higher chlorophyll and carotenoid by CARI and SIPI index. (Sophora alopecuroides L. was at a vigorously growing state and had a higher NDVI compared with the other three types of halophyte because of its greater canopy density. But its CARI and SIPI values were lower due to the influence of its flowers. (Sophora alopecuroides L.) and (Camphorosma monspeliaca L. subsp. lessingii(L.)) had stable REPs and BEPs, but REPs and BEPs of (Achnatherum splendens(Trin.)Nevski, Aellen, Alhagi sparsifolia shap) whose spectra red shift and spectra blue shift occurred concurrently obviously changed. There was little difference in spectral curves among the four types of halophyte, so the spectrum mixing phenomenon was severe. (Camphorosma monspeliaca L. subsp. lessingii (L.)Aellen) and (Alhagi sparsifolia shap) could not be separated exactly in a usual R/NIR feature space in remote sensing. Using the stepwise discriminant analysis, five indices were selected to establish the discriminant model, and the model accuracy was discussed using the validated sample group. The total accuracy of the discriminant model was above 92% and (Achnatherum splendens(Trin.)Nevski) and (Camphorosma monspeliaca L. subsp. lessingii(L.)Aellen) could be respectively recognized 100% correctly. PMID- 22295791 TI - [Effect of different snow depth and area on the snow cover retrieval using remote sensing data]. AB - For the needs of snow cover monitoring using multi-source remote sensing data, in the present article, based on the spectrum analysis of different depth and area of snow, the effect of snow depth on the results of snow cover retrieval using normalized difference snow index (NDSI) is discussed. Meanwhile, taking the HJ-1B and MODIS remote sensing data as an example, the snow area effect on the snow cover monitoring is also studied. The results show that: the difference of snow depth does not contribute to the retrieval results, while the snow area affects the results of retrieval to some extents because of the constraints of spatial resolution. PMID- 22295792 TI - [Hyperspectral acquisition system for tongue inspection based on X-Y scanning galvanometer]. AB - Hyperspectral was used for tongue inspection in the present work to resolve the problem that information of current research for tongue inspection was inadequate. A hyperspectral acquisition system based on X-Y scanning galvanometer was also proposed due to the high cost of the current hyperspectral apparatus. An experiment was made to test the ability of this system. By collecting the hyperspectral information of color pictures with size similar to the tongue, the results of experiment showed that this system can acquire more information of tongue than other methods, and this method can provide a new way for tongue inspection. PMID- 22295793 TI - [Validation of feasibility of virtual hyperspectral technology]. AB - To verify the virtual hyperspectral technology for acquiring the internal composition and structure information, the virtual hyperspectral system, which took apples as the test materials, was built. First, we detected the virtual hyperspectral system of the normal apples and ill apples. Then, the virtual hyperspectral of apple slices and apple slices with a piece of red optical filter embedded was detected. Finally, the reflection spectrum of normal apple, ill apple, apple slice and slice with a piece of red filter embedded was detected. The results showed that virtual hyperspectral, which can gain more information than reflection spectrum, could be used for detecting the variation of internal composition and structure. It is a strong evidence that this technology can be used in human body in the future. Virtual hpyerspectral is a new path applied to detecting the biological information, and it can be used for the multi information and cross-information detection simultaneously and systematically. More foundation for quick disease check-up in vivo was expected to be provided by this technology. PMID- 22295794 TI - [Microanalysis study on lignin distribution of wood with different growth stress level by SEM-EDXA]. AB - By virtue of FE-SEM and EDXA marked by Br element, the relationship between the lignin distribution and growth stress was micro-analyzed by normal wood of plantation Eucalyptus urophylla X E. grandis with different growth stress levels. The results indicated that the lignin contents of different cell wall layers were not related to the growth stress level, and the lignin content (from high level to low level) in sequence was cell corner, compound middle lamellae, S1, S2 and S3; The lignin contents in micro-morphological regions of wood fiber cell wall were decreased with the increase in growth stress and lignification process was delayed. PMID- 22295795 TI - [Preparation and characterization of quantum dots with polyacrylic acid modified method in water-soluble core-shell structure]. AB - Cd-Zn quantum dots (QDs) modified with thiourea was firstly prepared asthe cores, then the cores were coated with polyacrylic acid with PVP K-30 as the stabilizer in water-soluble reaction system. The water-soluble fluorescence QDs were the same size and stable. The water-soluble QDs were characterized by fluorescence emission spectra, infrared spectra (IR), and transmission electron microscopy (TEM). The effects of the nuclear QDs with different concentration under polyacrylic acid solution on the optical properties of QDs were also studied. The results showed that the nanoparticles of QDs modified with polyacrylic acid have more uniform particle distribution, and the main peak was blueshifted from 548 to 448 nm. C==O and C--O stretching vibration absorption peaks were 2092.8 and 1384.3 cm(-1) in infrared spectra, amide bond of C==O stretching vibration absorption peaks were 1644.5 cm(-1). The best concentration of nuclear QDs under polyacrylic acid solution was 2.67 mg x mL(-1). QDs prepared by this simple method have good stability and strong fluorescence intensity. The approach introduced in this paper will lay a solid foundation for biological markers and applications of QDs in the future. PMID- 22295796 TI - [Determination of metal by liquid electrode discharge atomic emission spectrometry with a new design]. AB - A liquid electrode discharge atomic emission spectrometry has been developed with a new design. Plasma fluctuation from the variations in the gap between the W anode and liquid cathode was eliminated by providing a sawtooth-shaped drainage structure. The sawtooth was placed at a distance of 2 mm from the glass capillary top. When a solution is pumped through a glass capillary, the liquid drop forms and rises and on reaching the maximum size collapses while the next drop forms. This results in a continuous change in the interelectrode distance which will cause the discharge current to change, plasma flickers and is extinguished. With the new design, the surface tension of the drop was destroyed before its growing up, and the solution was flowing along the drainage groove. The discharge can last for 3 hours at least with such arrangement. The analytical response curves for lead, chromium, cadmium, zinc, vanadium, nickel, copper, silver and cobalt demonstrated good linearity. The limit of detections of lead, chromium, cadmium, zinc, vanadium nickel, copper, silver and cobalt were determined to be 0.08, 0.61, 0.48, 1.60, 10.88, 0.48, 0.084, 0.048 and 0.27 mg x L(-1) respectively. PMID- 22295797 TI - [Distribution characteristics of heavy metals along an elevation gradient of montane forest]. AB - In the present paper, the concentrations of fourteen heavy metals (Fe, Al, Ti, Cu, Cr, Mn, V, Zn, Ni, Co, Pb, Se, Cd and As) were determined by ICP-AES and atomic absorption spectroscopy along an elevation gradient of montane forest. The results show that the elevation gradient had significant effects on the concentrations of Fe, Al, Ti, V, Pb and As. And the concentrations of Cu, Cr, Mn, Zn, Ni, Co, Se and Cd were not significantly affected by the elevation gradient. Because the studying area is red soil, the elevation gradient had significant effects on the concentrations of Fe, Al and Ti which are characteristic heavy metals of red soil, suggesting that the red soil at different elevations has different intensities of weathering desilication and bioaccumulation. Other heavy metals have different relationships with the elevation gradient, such as the concentrations of Cr, Zn and Cd were high at relatively high elevation and Pb and As were high at relatively low elevation. These results suggest that the different elevations of montane forest soils were polluted by differently types of heavy metals. PMID- 22295798 TI - [Determination of trace nickel in bi-based superconductor powder by inductively coupled plasma atomic emission spectroscopy after separation with anion exchange resin and extraction with methylbenzene]. AB - A new method for the determination of trace nickel in superconductor powder by ICP-AES was proposed. The instrument parameters were optimized, and the matrix effects as well as the method of eliminating interferences were also studied systemically. The results showed that matrix interference in the superconductor powder was serious when the amount of matrix increased, and the repeatability as well as the accuracy was poor, so it was necessary to used separation and preconcentration to improve the accuracy and precision. In this experiment, Ni diacetyl dioxime complexes were enriched by toluene extraction in alkaline condition after eliminating the interference of major element Bi and partial Pb, Sr, Ca and Cu by eluting with anion exchange resin, then the Ni-complexes were back extracted by diluted hydrochloric acid. The enrichment conditions were investigated in detail and the recovery rate of Ni was higher than 95%. Under the optimal condition, an artificial sample was analysed, the result showed that the found values were identical with reference values, and the RSD and detection limit were 1.9% and 0.19 microg x g(-1), respectively. The method has been applied to the determination of trace nickel in Bi-based superconductor powder samples with satisfactory results. PMID- 22295799 TI - [Quantitative determination of elements in plant samples by laser ablation inductively coupled plasma mass spectrometry]. AB - The 193 nm excimer laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used for the quantification of 13 elements (Li, B, Na, Mg, Al, K, Ca, Cr, Mn, Fe, Ni, Cu and Ba) in the plant samples (GBW070602, GBW070605 and GBW08514). Indium standard solution with known concentration was mixed into samples and used as an internal standard. Afterwards the samples were ground again and pressed to disks. NIST SRM 610 glass material reference standard was used as the external standard in the LA-ICP-MS measurements. In contrast to longer wavelength ablation techniques, in this experiment a round crater with low deposits could be achieved during ablation. And another study was done on the effect of homogenization over the powder disk It was clearly shown that the analytical results under the condition of 193 nm LA-ICP-MS, using NIST SRM 610 as the external standard for analysis of pressed disk of plant sample, are in good agreement with certified values. PMID- 22295800 TI - [Two steps elution method FI on-line adsorption and preconcentration coupled with FAAS for the determination of trace zinc]. AB - A flow injection two steps elution method on-line sorption and preconcentration system coupled to flame atomic absorption spectrometry (FAAS) was developed for the determination of trace Zn in water samples. The conventional elution procedure was divided into two steps: elution procedure and detection procedure. During the elution procedure, the eluent was pumped into KR by the suction of the peristaltic pump and through PTFE tube instead of peristaltic pump tube. By the new method, the dispersion of the analyte was decreased notably, and high absorbance peak value was achieved. Because the eluent was not through the peristaltic pump tube, the peristaltic pump tube was protected from being eroded. Emptying procedure was added in order to insure the veracity and repeatability of the experiment of every time. With 60 s (sample throughput of 37 x h(-1)) of sampling at a flow rate of 6.0 mL x min(-1), an enhancement factor (EF) of 28 (higher than 9 achieved by conventional elution method) and a detection limit (3sigma) of 0.35 x L(-1) were obtained. The precision (RSD, n=11) was 2.1% at the 20 microg x L(-1) level. When 0.1% phi triethannolamine was used as masking reagent, the recovery rate was from 98.7% to 99.6%. PMID- 22295801 TI - [Determination of aluminum in wheat flour food by microwave digestion-high resolution continuum source graphite furnace atomic absorption spectrometry]. AB - The contents of aluminum (Al) in four kinds of wheat flour food (noodle, dumpling wrapper, twisted cruller and soda biscuit) were determined by high resolution continuum source graphite furnace atomic absorption spectrometry (HR-CS GFAAS) combined with microwave digestion. The samples were completely digested by the mixture of HNO3 and H2O2 in closed polytetrafluoroethylene (PTFE) vessels. The conditions for microwave digestion, pyrolysis temperature and atomization temperature were optimized. The optimum experimental conditions were determined as follows. The microwave digestion was performed with HNO3/H2O2 7:1 (volume ratio), microwave power 1000 W and 190 degrees C for 40 minutes. The optimum pyrolysis temperature was 1350 degrees C and the optimum atomization temperature was 2400 degrees C. Magnesium nitrate solution with the concentration of 1 g x L( 1) was used as the matrix modifier. The correlation coefficient for the standard curve was 0.9999, the relative standard deviation (RSD) was from 1.7% to 2.4%, and the recovery for the samples was from 98.16% to 102.67%. The assay method for the determination of Al in wheat flour food established in this study has referential importance for the constituent of the correlated food standards. PMID- 22295802 TI - [Investigation on urinary arsenic concentration of city children in China]. AB - Children's urine sample was digested with nitric acid and drop-wise added hydrogen peroxide. After pre-reduction with ascorbic acid-thiourea, the total arsenic in sample solution was formed arsine in a flow injection hydride generation system and then was detected by atomic fluorescence spectrometry. Calibration curve was established every day and blank correction should be made for each analysis. Detection limit was 0.03 microg x L(-1). Analytical results of urine arsenic for 40 children sampling from Minhang District, Shanghai, were in the range of 0.5-1.5 microg x L(-1), possibly due to the foodstuffs of seafood and is not harmful to the human health PMID- 22295803 TI - [Nondestructive analysis of a Liuli ring of Warring State Period by EDXRF probe]. AB - A Liuli ring was nondestructively analyzed by EDXRF probe, to discuss the characteristic of chemical composition and the producing place of this Liuli ring. The result reveals that the chemical composition of this Liuli ring belongs to PbO-BaO-SiO2 system, which is similar to Chinese special ancient PbO-BaO-SiO2 glass dating from Chunqiu to East Han state. So, it was concluded that this Liuli ring was used Chinese special technology and formula, and was made in China. But on the appearance, this Liuli ring is not like a mature glass, but a faience or frit which is the compound of glass and crystal substance. PMID- 22295804 TI - [A fractal denoising method for astronomical spectral signal]. AB - To restore the continuum and the spectral lines from a noisy astronomical spectrum, then to measure the equivalent widths of the spectral lines, the fractal denoising method was firstly used in astronomical spectra in the present paper. The method is based on the distinguishing features, that is the local self similarities exist in an astronomical spectrum, while not in a random white noise signal. The experimental results show that the fractal denoising method is efficient in parameter measurements, such as equivalent widths for spectral lines, redshift of galaxies, and so on. In addition, the method can achieve data compression. The fractal method can be used in the mass spectra of LAMOST. PMID- 22295805 TI - [Study of instrumental line shape function of high-resolution Fourier transform infrared spectrometer with unequal field of view]. AB - Field of view (FOV) is an important contributor for instrumental line shape (ILS) function of high-resolution Fourier transform infrared spectrometer (FTS) only next to maximum optical difference. For the reason of optical design and layout, commonly, the measured FOV located in detector is not regularly rounded as original one. There exits more or less difference between the measured vertical FOV and measured horizontal one. In view of this case, the present paper replaces the generally circular area light source with an elliptical one, which is probably more suitable for actual FTS. At the same time, the factor maximum optical difference was considered. After these, the mathematic and graphic description about ILS function with unequal field of view (UFOV) was given Finally, comparison between measured spectrum with standard monoxide gas and calculated one with equal field of view (EFOV) and UFOV respectively was taken Experimental results show that the spectral residual from UFOV is less fluctuant than those from EFOV and its root mean square value is the smallest. All these indicate that the ILS function from UFOV is more accurate and suited to reflecting the response of high-resolution FTS than the one from EFOV. PMID- 22295806 TI - [Analysis of influence of satellite platform vibration on spectral imaging quality of dispersive imaging spectrometer]. AB - Satellite platform vibrations make dispersive imaging spectrometer and objects generate relative movement in exposure time, which seriously affects the quality of spectral data. PHI was made as the model of dispersive spectrometer, the impact of pitch, roll, yaw and three-axis vibrations on spectral data were studied chiefly, and distorted spectral data cubes under various vibrations were simulated, then the general law of distortion spectral cube caused by satellite platform vibration was gained. The results show that the dispersive imaging spectrometer has high requirements for reduction of vibration amplitude. A small amplitude also can generate great influence on spectrum. The spectral data must be corrected and the vibration of satellite platform must be reduced to ensure the authenticity of spectrum. PMID- 22295807 TI - [The optimizing design and experiment for a MOEMS micro-mirror spectrometer]. AB - A MOEMS micro-mirror spectrometer, which uses micro-mirror as a light switch so that spectrum can be detected by a single detector, has the advantages of transforming DC into AC, applying Hadamard transform optics without additional template, high pixel resolution and low cost. In this spectrometer, the vital problem is the conflict between the scales of slit and the light intensity. Hence, in order to improve the resolution of this spectrometer, the present paper gives the analysis of the new effects caused by micro structure, and optimal values of the key factors. Firstly, the effects of diffraction limitation, spatial sample rate and curved slit image on the resolution of the spectrum were proposed. Then, the results were simulated; the key values were tested on the micro mirror spectrometer. Finally, taking all these three effects into account, this micro system was optimized. With a scale of 70 mm x 130 mm, decreasing the height of the image at the plane of micro mirror can not diminish the influence of curved slit image in the spectrum; under the demand of spatial sample rate, the resolution must be twice over the pixel resolution; only if the width of the slit is 1.818 microm and the pixel resolution is 2.2786 microm can the spectrometer have the best performance. PMID- 22295808 TI - [Design and study of a high resolution vacuum ultraviolet imaging spectrometer carried by satellite]. AB - A high resolution vacuum ultraviolet imaging spectrometer prototype carried by satellite applied to the atmosphere detection of particles distribution in 115 300 nm was developed for remote sensing. First, based on the analysis of advanced loads, the optical system including an off-axis parabolic mirror as the telescope and Czerny-Turner structure as the imaging spectrometer was chosen Secondly, the 2-D photon counting detector with MCP was adopted for the characteristic that the radiation is weak in vacuum ultraviolet waveband. Then the geometric method and 1st order differential calculation were introduced to improve the disadvantages that aberrations in the traditional structure can not be corrected homogeneously to achieve perfect broadband imaging based on the aberration theory. At last, an advanced example was designed. The simulation and calculation of results demonstrate that the modulation transfer function (MTF) of total field of view is more than 0.6 in the broadband, and the spectral resolution is 1.23 nm. The structure is convenient and predominant. It proves that the design is feasible. PMID- 22295809 TI - [Influence of surface roughness on degree of polarization of biotite plagioclase gneiss varying with viewing angle]. AB - Polarized reflectance is influenced by such factors as its physical and chemical properties, the viewing geometry composed of light incident zenith, viewing zenith and viewing azimuth relative to light incidence, surface roughness and texture, surface density, detection wavelengths, polarization phase angle and so on. In the present paper, the influence of surface roughness on the degree of polarization (DOP) of biotite plagioclase gneiss varying with viewing angle was inquired and analyzed quantitatively. The polarized spectra were measured by ASD FS3 spectrometer on the goniometer located in Northeast Normal University. When the incident zenith angle was fixed at 50 degrees, it was showed that on the rock surfaces with different roughness, in the specular reflection direction, the DOP spectrum within 350-2500 nm increased to the highest value first, and then began to decline varying with viewing zenith angle from 0 degree to 80 degrees. The characterized band (520 +/- 10) nm was picked out for further analysis. The correlation analysis between the peak DOP value of zenith and surface roughness showed that they are in a power function relationship, with the regression equation: y = 0.604x(-0.297), R2 = 0.985 4. The correlation model of the angle where the peak is in and the surface roughness is y = 3.4194x + 51.584, y < 90 degrees , R2 = 0.8177. With the detecting azimuth farther away from 180 degrees azimuth where the maximum DOP exists, the DOP lowers gradually and tends to 0. In the detection azimuth 180 dgrees , the correlation analysis between the peak values of DOP on the (520 =/- 10) nm band for five rocks and their surface roughness indicates a power function, with the regression equation being y = 0.5822x(-0.333), R2 = 0.9843. F tests of the above regression models indicate that the peak value and its corresponding viewing angle correlate much with surface roughness. The study provides a theoretical base for polarization remote sensing, and impels the rock and city architecture discrimination and minerals mapping. PMID- 22295810 TI - [Spectral line shift property of prism dispersive imaging spectrometer]. AB - In order to study the spectral line shift property of prism-dispersive imaging spectrometer, the influencing factors and mechanisms of spectral line shift were presented, and the mathematical model based on linear optics model was established to describe the spectral line shift property. Code V API functions was used, in Matlab environment, to verify the validity of mathematical model, and the sensitivity coefficient of spectral line shift was analyzed. Results indicate that rigid body motion of optical mirror surface generated by environmental variation is the key causation of spectral line shift. When the decenter of mirror surface is no more than 0.2 mm and the tilt is less than 0.02 degrees, the value of spectral line shift of different wavelengths at different fields is equivalent, and the error is less than 0.1 pixel. Spectral line shift due to mirror rigid body motion is linear and independent, and the total shift of the spectral line is the algebraic sum of values produced by the single freedom of motion (DOF) of single mirror surface. The mathematical model based on linear optics model can be used to study the spectral line shift property of the prism dispersive imaging spectrometer. It will provide some guidance for spectral calibration and spectral property analysis under complex work condition. PMID- 22295811 TI - [Observation on therapeutic effect of acupuncture combined with medicine on mild cognition disorders in patients with post-stroke]. AB - OBJECTIVE: To explore the curative effect and safety of acupuncture for mild cognitive disorders after stroke. METHODS: Randomized controlled trial was adopted and one hundred cases conforming to criteria were divided into a combined acupuncture and medication group (group A) and a medication group (group B), 50 cases in each group. The basic treatment of cerebrovascular disease was applied in two groups. The group A treated was with acupuncture at Baihui (GV 20), Shenting (GV 24) and Qucha (BL 4) etc. and oral administration of Nimodipine. In group B, Nimodipine was taken orally. The treatment lasted for 3 months, the scores of Mini-Mental State Examination (MMSE), modified Hasegawa Dementia Scale (HDS-R) and Barthel Index (BI) were observed before and after treatment in two groups. RESULTS: The total effective rate in group A was 66.7% (32/48), which was superior to 30.4% (14/46) in group B (P < 0.05). The scores of MMSE, HDS-R and BI after treatment were apparently improved as compared with those before treatment in two groups (all P < 0.01). The improvements in group A were superior to those in group B (all P < 0.05). There was no adverse event reported during the treatment in two groups. CONCLUSION: Acupuncture can improve activity of daily living and has significant effect in treating mild cognition disorders after stroke without adverse reactions. PMID- 22295812 TI - [Observation on curative effect of glomerular pathological proteinuria treated with heat-producing needling]. AB - OBJECTIVE: To observe the differences of curative effect of glomerular pathological proteinuria treated with combined therapy of acupuncture and medicine or simple medicine. METHODS: Two hundred and forty cases of glomerular pathological proteinuria were divided into a combined therapy of acupuncture and medicine group (combined therapy group), a medicine group I and a medicine group II, 80 cases in each group. In combined therapy group, Pishu (BL 20) and Zhishi (BL 52) were punctured by heat-producing needling; Terazosin Hydrochloride, Bisoprolol Fumarate tablets or compound Reserpinum Triamterene tablet were applied with oral administration when accompanied by high blood pressure, to control the blood pressure within 130/80 mmHg. In medicine group I , Renin Angiotensin-Aldosterone system (RAAS) interruption method was applied to control blood pressure; Benazepril Hydrochloride and Telmisartan were applied with oral administration to keep blood pressure in satisfying level, below 125-130/75-80 mmHg. In medicine group II, placebo was orally taken, and the medicine therapy which was same as that in combined therapy group was applied when accompanied by high blood pressure. Quality low protein and low salt and fat diet were applied in all groups. The Chinese medicine syndrome score, laboratory indices and curative effect were observed in all groups before and after treatment. RESULTS: The total effective rate was 86.3% (69/80), 61.3% (49/80) and 17.5% (14/80) respectively in combined therapy group, medicine group I and medicine group II, indicating that the curative effect in combined therapy group was superior to that in other groups (P < 0.01, P < 0.05), and it in medicine group I was superior to that in medicine group II (P < 0.01). The Chinese medicine syndrome score was markedly reduced in combined therapy group (P < 0.01), and there was no obvious change in other groups (both P > 0.05). Urinary albumin (UMA) and urinary protein in 24 hours were notably reduced in combined therapy group and medicine group I (all P < 0.01), and it was more obviously in combined therapy group than that in other groups (P < 0.01, P < 0.05). The blood pressure was markedly reduced in all groups (all P < 0.05) after treatment, and there was no significant change in indices of liver and kidney functions (all P > 0.05). CONCLUSION: The curative effect of heat-producing needling method is good for treating glomerular pathological proteinuria, better than that of RAAS interruption method. PMID- 22295813 TI - [Observation on influence of bone metabolism biochemical indices of senile osteoporosis treated with distant acupuncture and nearby tuina]. AB - OBJECTIVE: To observe the influence of bone metabolism biochemical indices of senile osteoporosis treated with distant acupuncture and nearby tuina, and to probe the better therapy for senile osteoporosis. METHODS: Sixty-four cases were randomly divided into an observation group and a control group. In control group (30 cases), Calcium Carbonate D, Tablet was orally taken for 12 weeks continuously. In observation group (34 cases), "distant acupuncture and nearby tuina" therapy were applied, that was puncture at Weizhong (BL 40) and Taixi (KI 3), and tuina therapy on lumber region, 30 times treatment was applied totally. The changes of blood calcium (Ca), phosphorus (P), ALP, BGP and urine DPD in bone metabolism biochemical indices were observed and compared before and after treatment in two groups. RESULTS: There were significant differences in P, BGP, DPD in bone metabolism biochemical indices in both groups before and after treatment (P < 0.05, P < 0.01), the contents of blood P decreased, blood BGP increased and urine DPD decreased. But, there were no significant differences in above indices between two groups. CONCLUSION: The calcium with oral administration and "distant acupuncture and nearby tuina" therapy can effectively improve the bone metabolism biochemical indices of senile osteoporosis, and they have positive significance in prevention of osteoporosis, however, it hasn't proved that which method is better for calcium protecting. PMID- 22295814 TI - [Clinical observation on the long-term effect of warming-promotion acupuncture on lumbar spinal stenosis]. AB - OBJECTIVE: To observe the difference effects between warming-promotion acupuncture and normal acupuncture on lumbar spinal stenosis (LSS). METHODS: Sixty cases of LSS were randomly divided into a normal acupuncture group (30 cases) and a warming-promotion acupuncture group (30 cases). The two groups both chose Dazhui (GV 14), Mingmen (GV 4), Jiaji (EX-B 2),etc. Normal method without special manipulation was used in normal acupuncture group, while the warming promotion manipulation was used in warming-promotion acupuncture group, all once daily, 10 treatments made one session. Compare the symptoms and spinal cord function of LSS, quality of life (QOL)and clinical effect in the two groups. RESULTS: The comprehensive score of symptoms of LSS in warming-promotion group 3 months after treatment was 6.30 +/- 1.92, while that in normal acupuncture group was 4.67 +/- 13.70. The score of spinal cord function in warming-promotion group after treatment was 7.03 +/- 1.03, while that in normal acupuncture group was 6.33 +/- 1.12. The score of QOL in warming-promotion group after treatment was 53.67 +/- 8.91, while that in normal acupuncture group was 64.50 +/- 16.69. All the differences between these scores in two groups were statistically significant (all P < 0.05). The total effective rate was 90.0% (27/30)in warming-promotion group, and 80.0% (24/30) in normal acupuncture group. The effect of warming promotion group was better than that in normal acupuncture group (P < 0.05). CONCLUSION: In the field of treating LSS, the effect of warming-promotion acupuncture is better than normal acupuncture. PMID- 22295815 TI - [Treatment of peripheral facial paralysis with acupuncture at Renying (ST 9) mainly cooperated with stellate ganglion block: a randomized controlled trial]. AB - OBJECTIVE: To explore the better therapy for peripheral facial paralysis. METHODS: One hundred and twenty patients were randomized into three groups: a common acupuncture group: acupuncture at Yangbai (GB 14), Sibai (ST 2) and Yingxiang (LI 20) as main acupoints, a ST 9 group: acupuncture at Renying (ST 9) as main and a ST 9 plus SGB group: acupuncture at Renying (ST 9) as main cooperated with stellate ganglion block (SGB). Once daily, 7 treatments made one session. After three sessions of treatment, the latency period and amplitude of evoked potential in ENoG, R1 value and R2 value of blink reflex were compared before and after the treatment in different groups separately. The total therapeutic effect was evaluated after treatment. RESULTS: All the treatments shortened the latency period of ENoG, and elevated the amplitude evoked potential significantly. After treatment, the latency period in ST 9 plus SGB group was reduced significantly as compared with common acupuncture group (P < 0.05). The amplitude of evoked potential in ST 9 group was increased significantly as compared with the other two groups (both P < 0.05). After treatment, in each group, R1 and R2 values were shortened significantly. The difference values of R1 and R2 in ST 9 group and ST 9 plus SGB group were all significantly higher as compared with common acupuncture group (both P < 0.05). Additionally, the difference value of R1 in ST 9 plus SGB group was higher significantly than that in ST 9 group (P < 0.05). The clinical cured and remarkably effective rate was 87.5% (35/40) in ST9 plus SGB group, which was higher than 77.5% (31/40) in ST 9 group, and 65.0% (26/40) in common acupuncture group (P < 0.05). CONCLUSION: As compared with common acupuncture group, ST 9 group and ST 9 plus SGB group achieve the much superior efficacy on peripheral facial paralysis. The treatment with ST 9 acupuncture and SGB can better repair the early reflex induced by the injury of facial nerve. PMID- 22295816 TI - [Acupuncture at Tianying-point with two needles for back muscles fasciitis]. PMID- 22295817 TI - [Clinical observation on shoulder periarthritis treated with Bo's abdominal acupuncture in stages]. AB - OBJECTIVE: To probe an effective therapeutic method for the treatment of shoulder periarthritis. METHODS: Ninety-six patients were randomly divided into an acupuncture group and an abdominal acupuncture group, 48 cases in each. According to clinical pathological staging, the disease was divided into pain stage and adhesion stage. In abdominal acupuncture group, 24 cases were in pain stage and treated with acupuncture at Zhongwan (CV 12), Shangqu (KI 17) on the healthy side, Huaroumen (ST 24) on the affected side and others; 24 cases were in adhesion stage and treated with acupuncture at Zhongwan (CV 12), Xiawan (CV 10), Qihai (CV 6), Guanyuan (CV 4) and others. In acupuncture group, there were 24 cases in either pain stage or adhesion stage, treated with acupuncture at Jianyu (LI 15), Jianliao (TE 14), Jianzhen (SI 9) and others on the affected side. In either group, the treatment was given three times a week, three weeks treatment made one session, 9 treatments totally. Before and after treatment, the Visual Analogue Scale (VAS) was adopted for pain assessment and functional activity score (Melle score) was for shoulder joint function assessment for all the patients. RESULTS: After one session treatment, the efficacy was compared between two groups. In abdominal acupuncture group, the total effective rates were 95.8% (23/24) and 91.7% (22/24) in pain stage and adhesion stage respectively. In acupuncture group, the total effective rates were 91.7% (22/24) and 79.2% (19/24) in pain stage and adhesion stage respectively. The efficacy in adhesion stage of abdominal acupuncture group was better than that in acupuncture group (P < 0.05). After treatment, VAS score and Melle score were all reduced as compared with those before treatment in either group (all P < 0.01), in which, the reducing ranges in abdominal acupuncture group were larger than those in acupuncture group (all P < 0.05). CONCLUSION: Abdominal acupuncture achieves a significant efficacy on shoulder periarthritis in stages. It is an effective therapy for shoulder periarthritis. PMID- 22295818 TI - [Objection on specific points]. PMID- 22295819 TI - [Clinical comparative study on the influence of acupoint sticking therapy in dog days and in non-dog days to the quality of life of allergic rhinitis patients]. AB - OBJECTIVE: To observe and compare the influence of acupoint sticking therapy in dog days and in non-dog days to the quality of life of allergic rhinitis patients. METHODS: Fifty-five cases were divided into group A (the acupoint sticking therapy in dog days group, 28 cases) and group B (the acupoint sticking therapy in non-dog day group, 27 cases) randomly. The acupoint sticking therapy description (Dazhui (GV 14), Fengmen (BL 12), Feishu (BL 13) etc. was used in both groups. Five times of acupoint sticking therapy were given to patients in group A during dog days in 2010, while another 5 times of acupoint sticking therapy were given to patients in group B before the dog days. The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was used to evaluate the effects before, after and half a year after treatment. RESULTS: The scores of behavior problems, nasal symptoms and quality of life in RQLQ of both groups all decreased after treatment (all P < 0.01). The score of emotion reaction of group A in the follow-up period decreased compared with that before treatment (P < 0.05). The scores of non-nasal-or-ocular symptoms, ocular symptoms and emotion reaction after treatment and in the follow-up period all decreased than those before treatment (P < 0.01, P < 0.05). The decreasing degrees of scores of non nasal-or-ocular symptoms, ocular symptoms, emotion reaction and quality of life after treatment and in the follow-up period in group A were all greater than those in group B (P < 0.01, P < 0.05). CONCLUSION: In the same season, both acupoint sticking therapy in dog days and in non-dog dags can improve the symptoms of allergic rhinitis, but the improving degree to quality of life in the method of acupoint sticking in dog days is greater. PMID- 22295820 TI - [Discussion on the innovative needling methods of "warm reinforcing technique" and "cold reducing technique" invented by professor ZHENG Kui-shan]. AB - The innovated needling methods of "warm reinforcing technique" and "cold reducing technique" by professor ZHENG Kui-shan was analyzed. The discussion on these methods was done in comparison with the techniques of "setting the mountain on fire" and "penetrating the heaven coolness". The innovations and the clinical application advantages were explored. ZHENG's "warm reinforcing technique" and "cold reducing technique" were based on the techniques of setting the mountain on fire" and "penetrating the heaven coolness". These techniques were the complex of the simple techniques of reinforcing and reducing, such as rotating, lifting and thrusting, assistant reinforcing and reducing, as well as reinforcing and reducing by keeping the acupoint open or not. Of those different techniques, reinforcing and reducing by rotating needling and the assistant method are recommended by prof. ZHENG and they are the characteristics of ZHENG's needling technique. Compared with the techniques of "setting the mountain on fire" and "penetrating the heaven coolness", "warm reinforcing technique" and "cold reducing technique" are simple in operation and widely applied in clinical practice. Moreover, these techniques have the same efficacy as the techniques of "setting the mountain on fire" and "penetrating the heaven coolness". PMID- 22295821 TI - [Acupuncture for 30 cases of epiphora]. PMID- 22295822 TI - [Evidence of "who knows acupuncture believes the importance of the pressing hand" in ancient literatures and its clinical significance]. AB - According to the records in ancient Chinese literatures such as Lingshu (Miraculous Pivot), Nanjing (The Yellow Emperor's Canon of 81 Difficult Issues), Jinzhen fu (Odes to Golden Needles) and Zhenjiu Dacheng (Compendium of Acupuncture and Moxibustion), the importance of pressing hand has been always stressed. The role of the pressing hand can irreplaceable by the puncturing hand. The touching and pressing with the pressing hand assist on the accurate location of acupoint. The plucking technique may invigorate meridian qi and promote the arrival of qi. Inserting the needle against the finger nail of the pressing hand avoids or alleviates pain to the largest extent. Detecting along meridian and pressing technique main induce qi getting to the affected area. This paper introduces the importance of pressing hand, aiming to suggest the clinical physicians pay more attentions to the effect of the pressing hand in acupuncture practice. PMID- 22295823 TI - [Thirty cases of PCOS treated by the according to stage moxibustion on medicinal cake and acupuncture]. PMID- 22295824 TI - [The academician SHI Xue-min 's research on "syncope" of Miraculous Pivot: Meridians]. AB - Based on decades of research from Chinese ancient medical classics, with new understandings of the meridian differentiations, the academician SHI Xue-min made a further research on the original intention of the "syncope" of Miraculous) Pivot: Meridians. Furthermore, due to his clinical practice, the specific applications were summarized to guide the clinical treatment, such as the locations of acupoints and the techniques of acupuncture, which could be evidenced by favorable therapeutic improvements. PMID- 22295825 TI - [Twenty-four cases of chronic ulcerative colitis treated by acupuncture combined with Chinese herb]. PMID- 22295826 TI - [Evaluation of the post-effect of acupuncture at Sanyinjiao (SP 6) under sleep deprivation by resting-state amplitude of low-frequency fluctuation: a fMRI study]. AB - OBJECTIVE: To discuss the central modulating mechanism of Sanyinjiao (SP 6) and the amplitude of low-frequency fluctuation (ALFF) differences of the functional brain regions between SP 6 and sham acupoint. METHODS: Sixteen volunteers accepted right Sanyinjiao (SP 6) (SP 6 group) or right sham (sham group) acupuncture for two times after 24 h sleep deprivation (SD), there was two weeks between two acupunctures. The needle was retained for 4 minutes and the brain fMRI scanning was performed by 3.0 TMR every time. The ALFF consequent data was processed by REST. One-sample t-test and two-pair t-test were performed by SPM5. RESULTS: SP 6 group mainly caused ALFF change in inferior parietal lobule, posterior cingulated while sham group in precuneus, posterior cingulated. SP 6 group increased ALFF in left fusiform temporal gyrus, medial frontal gyrus with no decreased regions compared with sham group. CONCLUSIONS: Retaining needle dose influence the activity of the brain region during resting-state in both group, especially the mood-related regions. And its mechanism is probably that the relevant effect is carried out by regulating function to target organs of complex brain network comprised of relevant functional center and related brain region. There are differences between SP 6 and Sham acupoint. PMID- 22295827 TI - [Effect of artemisia burning products on antioxidant enzymes in serum of SAMP8 mouse]. AB - OBJECTIVE: To explore the anti-aging effect of artemisia burning products (ie. smoke of moxibustion) and its proper intervention parameters. METHODS: According to factorial experiment design, 70 SAMP8 mice were randomly divided into one model group (group M) and 6 intervention groups: low concentration with 15 min group (group A1), low concentration with 30 min group (group A2), middle concentration with 15 min group (group B1), middle concentration with 30 min group (group B2), high concentration with 15 min group (group C1), high concentration with 30 min group (group C1). There were 10 cases in each group. Ten age-matched SAMR1 mice were used as normal group (group Z). All the mice in the 6 intervention groups were fumed with artemisia burning products of different concentration and time. The content of serum malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and glutathione reductase (GSH-Px) were tested. RESULTS: MDA content in group M was significantly higher than that in group Z (both P < 0.05), while SOD and GSH-Px activity were significantly lower in group M than that in group Z (both P < 0.05). Results of MDA, SOD and GSH-Px in 6 intervention groups were either of no statistically significant differences, or better than that in group M. Among 6 intervention groups, results of MDA and GSH Px were better in group B1, while the result of SOD was better in group B2. Time factor didn't make any difference, while concentration of artemisia burning products is meaningful. As to SOD and GSH-Px, there's a strong interaction between the two factors. CONCLUSION: With certain concentration and time period, the intervention of artemisia burning products can exert anti-aging effect by increasing antioxydative capability and reducing metabolites of free radicals. Middle concentration and 30 minutes are recommended when intervened with artemisia burning products. PMID- 22295828 TI - [Case of limb dysfunction caused by hand-foot-mouth disease]. PMID- 22295829 TI - [Chronic pharyngitis treated by garlic moxibustion]. PMID- 22295830 TI - [Comparison of effects of acupuncture-assisted anesthesia with different acupoint combination in gynecologic laparoscopy operation]. AB - OBJECTIVE: To explore the best acupoint combination of acupuncture-assisted anesthesia in gynecologic laparoscopy operation. METHODS: Ninety patients, with American Society of Anesthesiologists (ASA) physical status I - II, and scheduled for elective gynecologic laparoscopy operation, were randomly divided into 3 groups, 30 cases in each group. Group I received only general anesthesia, group II and group III received general anesthesia after Han's acupoint nerve stimulator (HANS) administered for 30 min, bilateral Zusanli (ST 36) and Sanyinjiao (SP 6) were selected for group II, and bilateral Hegu (LI 4) and Taichong (LR 3) were selected for group III. During operation, the concentration of Seveflurine was adjusted to maintain NTS at D1-D2. The change of ETsev value was recorded, the heart rate (HR) and blood pressure (BP) were observed, and the time from the end of operation to extubation, awake time were recorded adverse events such as restlessness, shivering, postoperative pain, nausea and vomiting, cases of respiratory depression, the analepsia quality, the time of first anus exhaust, the awaking of patient in operation and satisfactory of patients after surgery were recorded so as to evaluate the effect of acupuncture anesthesia. RESULTS: Compared with group I, the ETsev in group II was decreased 35% (P < 0.05), group ifi was decreased 25% (P < 0.05), with a significant difference between group II and group III (P < 0.05). BP and HR had more stability in group II and group III, the best in group II. As for the time from the end of operation to extubation and the time from the end of operation to open the eye on command, group I was the longest (all P < 0.05), group III was longer, group II was the shortest. The score of restlessness, postoperative pain, vomiting and in analepsia were the highest in group I (all P < 0.05), higher in group III and the lowest in group II. Consciousness score was lowest in group I (P < 0.05). As for the satisfactory of patient after operation, it was higher in group II and group IIII (both P < 0.05 ) than group I. The time of first anus exhaust in group II and group III were significantly shorter than that in group I (both P < 0.05). CONCLUSION: Han's acupoint nerve stimulator has a certain adjuvant action for general anesthesia and analgesia and acupuncture point combination with both Zusanli (ST 36)and Sanyinjiao (SP 6) have the best effect in gynecologic laparoscopy operation. It can decrease the dosage of anaesthetic, has a stable effect on HR and BP during the surgery and has a better quality of analepsia. PMID- 22295831 TI - [Discussion on point selection and compatibility of acupuncture formula]. AB - Acupuncture prescription is the key and effectiveness guarantee to acupuncture treatment. Proper selection of acupoint is directly related to the therapeutic effect of acupuncture. Several issues were discussesed, which were acupoint indications, clinical syndrome differentiation and acupoints selection. Acupuncturists should grasp the acupoints characteristic and pay attention to syndrome differentiation. Also they should have flexible selection of acupoints and keep pace with research updates when facing clinical problems in order to maximize the curative effect of acupuncture. PMID- 22295832 TI - [Study on inter-individual variability of cerebral response to acupuncture with fMRI]. AB - OBJECTIVE: Effects of inter-individual variability on fMRI of acupuncture were observed and the possible influencing factors were further analyzed. METHODS: Twenty-six healthy volunteers were selected. And acupuncture was applied at Zusanli (ST 36) on the left side with even manipulation. The same experimental designation and data collecting reference were adopted to collect functional data. Then, the same data processing method was applied for analyzing individual data. Data which did not confirm with data analyzing qualification were rejected. The 26 individual data which met the requirement were taken randomly for 5 times according to the principle of random group division. Five groups named with A, B, C, D and E were thus generated with 11 samples in each. Images were processed with the AFNI software for every group, and the activated brain areas were revealed. RESULTS: Activated areas in the brain were observed in all the 5 groups, and the results vary a lot among different groups. Decreased signals of activated brain areas were observed in group C, while increased signals were seen in group D. Partial increasing and partial decreasing signals appeared in the other 3 groups. Compared with other groups, group D demonstrated totally different activated areas. The rate of difference among different groups is 46.7% 100.0%, and most of the differences were over half of the activated areas. CONCLUSION: Under the pre-requisites of strict control of experimental designation, acupuncture method, data collecting and processing, great differences have been found in the activated areas of the brain. It indicates that obvious individual differences existes in the activated areas of the brain with acupuncture. And the difference may greatly influence the researching result of fMRI as well as conclusions of those results. PMID- 22295833 TI - [Thinking on teaching reform of acupuncture and moxibustion science]. AB - The current problem of acupuncture and moxibustion education is that incomplete and unsystematic content, simple and boring teaching method, and poor-level training in clinical practice. Therefore, students lack study initiative, dedication and passion for their professional study. The complete and systematic educational contents and innovative teaching methods of Acupuncture and Moxibustion Science are proposed. It also proposes innovative educational reform which is student-centered to foster students' professional skills in clinical practices. PMID- 22295834 TI - [Case of spinal and bulbar muscular atrophy]. PMID- 22295835 TI - [Comparative study on therapeutic effect between SXDZ-100 and SDZ-II on chronic functional constipation]. AB - OBJECTIVE: To compare the therapeutic effects between the Hwato neuro and muscle stimulator (SXDZ-100) and the regular electronic stimulator (SDZ-II) on chronic functional constipation. METHODS: Sixty-four cases of chronic functional constipation were randomly divided into a (SXDZ-100) observation group (n = 33) and SDZ-II control group (n = 31). For the SXDZ-100 group, under the considerations of patients' endurance, Zhigou(TE 6) and Tianshu (ST 25), Zusanli (ST 36) and Shangjuxu (ST 37) were punctured and then the courle of acupoints on the same side were connected with SXDZ-100 apparatus in reinforcing and reducing by twirling and rotating manipulation wave for 30 min, while in the control group SDZ-II apparatus was applied in the same way mentioned above with disperse-dense wave at frequency of 1Hz/20Hz for 30 min. By means of clinical therapeutic effect evaluation and clinical symptom score, the contrast between two groups can be made. RESULTS: Although the total effective rates were both 100.0%, the rate of short term effects in SXDZ-100 group (54.6%, 18/33) is significantly higher than that in SDZ-II group (29.0%, 9/31) (P < 0.05). After the treatment, the clinical symptom scores in both groups decreased significantly (both P < 0.05). And the therapeutic effective indices of the SXDZ-100 group were significantly higher than those of the SDZ- II group (P < 0.05). CONCLUSION: The therapeutic effect of Hwato neuro and muscle stimulator (SXDZ-100) on chronic functional constipation is superior to that of a regular electronic stimulator (SDZ-II). PMID- 22295836 TI - [CHENG Dan-an's experience of study in Japan]. AB - The first hand documents, the process and achievements of Mr. CHENG' s study in Japan in the 1930s were investigated in order to provide basic information to explore the original academic thoughts of Mr. CHENG and the Chengjiang Acupuncture School. It was concluded that the experiences of Mr. CHENG's study in Japan had significant influence on enriching and developing his academic thoughts. It has not only enhanced his confidence in therapeutic effect of moxibustion and revival of Chinese acupuncture, but also established the foundation for the reform of needles and expansion of the domain of Chinese acupuncture and its development after returning home. PMID- 22295837 TI - [Electroacupuncture for 12 cases of cervical spondylotic amyotrophy]. PMID- 22295838 TI - [Review on hospital infection administration of acupuncture manipulation with filiform needles]. AB - To analyze the relevant documents of hospital infection administration of acupuncture manipulation with filiform needles and acupuncture aseptic technique with filiform needles. The current situation is that acupuncturists have understanding insufficiency in hospital infection management, lack the sterile concepts and consciousness of disinfection and isolation. Aseptic technic principles aren't strictly followed; disinfection and isolation systems are unsound; sanitary condition of hand of medical staff is unsatisfied; and there is shortness in traditional long filiform needle manipulation. In future, we should explore the new model of hospital infection administration of acupuncture manipulation with filiform needles from implementations of relevant rules of hospital infection administration, establishment and supervision of sound corresponding system, further research of manipulation of filiform needles and formulation of septic technic criterion of filiform needles. PMID- 22295839 TI - [Thirty-five cases of intractable back pain treated with acupuncture according to symptom differentiation]. PMID- 22295840 TI - [Met-analysis on randomized controlled clinical trials of acupuncture and moxibustion on constipation]. AB - OBJECTIVE: To assess the efficacy of acupuncture and moxibustion on constipation. METHODS: A retrieval on literatures concerning treatment of constipation with acupuncture was carried out in databases of VIP, CNKI, WANFANG and PubMed. And meta-analyses were conducted on randomized controlled trial (RCT) and controlled clinical trial (CCT) which met the enrolling requirements. RESULTS: A total number of 15 papers involving 1 052 patients were concluded. The result indicated that the curative rate of acupuncture and moxibustion on constipation is better than ordinary medication (RR = 1.92, 95% CI 1.61-2.30, Z = 7.18, P < 0.000 01). And statistical significance can be found between acupuncture-moxibustion treatment and the routine medicine treatment (RR = 1.26, 95% CI 1.18-1.34, Z = 7.26, P < 0.000 01). In the comparison of abdominal pain, defecation duration and general symptom scores, statistical significance can be found between the differences of acupuncture and moxibustion group and control group (abdominal pain: WMD = -0.22, 95% CI-0.32-0.12, Z = 4.28, P < 0.000 1; defecation duration: WMD = -0.47, 95% CI-0.79-0.15, Z = 2.85, P < 0.004; general symptom scores: WMD = -0.41, 95% CI-0.79-0.03, Z = 2.13, P = 0.03). CONCLUSION: Acupuncture and moxibustion is effective to treat constipation. It has certain advantage when compare with the routine medication treatment. However, since singleness still exists in the index of assessment on therapeutic effect of constipation, and the number of RCT and CCT literatures, especially high-quality, large samples and multi-center reports were still not enough, further studies are still necessary for approving the above conclusions. PMID- 22295841 TI - [Diagnosis and treatment of idiopathic semen quality abnormalities]. AB - Idiopathic semen quality abnormalities include idiopathic oligozoospermia, asthenospermia, teratospermia, azoospermia and idiopathic abnormal semen liquefaction. The possible causes of idiopathic semen quality abnormality include age, non-inflammatory function changes of subsidiary gonadal organs, infection, genetic abnormalities, sperm mitochondrial changes, effects of environmental pollutants, and subtle hormonal changes. The diagnosis of idiopathic oligozoospermia, asthenospermia, teratospermia and azoospermia require detailed inquiry of the case history, physical examination, semen analysis, determination of reproductive hormones, genetic and immunological examinations, and so on, to exclude possible known causes. The treatment of idiopathic oligozoospermia, asthenospermia, and teratospermia may involve the use of Western medicines, such as clomiphene citrate, tamoxifen, recombinant FSH, Andriol, compound zinc and selenium, L-carnitine, recombinant growth hormone and pentoxifylline, the application of traditional Chinese drugs, or the combination of traditional Chinese and Western medicine. Idiopathic azoospermia can be treated by assisted reproductive technology based on the medication of spermatogenesis-promoting drugs, and idiopathic abnormal semen liquefaction can be managed with traditional Chinese drugs, integrated traditional Chinese and Western medicine, or in vitro semen processing technology. With the development of diagnostic technology, it is expected that more specific therapeutic methods will be established for idiopathic semen quality abnormalities and their incidence will be reduced. PMID- 22295842 TI - [Fasudil improves erectile function of hypertensive rats]. AB - OBJECTIVE: To investigate the effect of fasudil, an inhibitor of Rho kinase, on the erectile function of hypertensive rats and its action mechanism. METHODS: Twenty 12-week-old healthy male Sprague-Dawley rats were randomly divided into groups A (control), B (hypertension) and C (fasudil treatment). After establishment of the hypertension model, group C received intraperitoneal injection of fasudil at 30 mg/(kg x d), while A and B normal saline only. At 10 weeks after surgery, we measured the corpus cavernosum pressure/mean carotid arterial pressure (ICPmax / MAP), and the expression levels of ROCK1 and ROCK2 proteins in the corpus cavernosum of the rats by Western-blot. RESULTS: The systolic blood pressure (mmHg) and the expressions of ROCK1 and ROCK2 proteins were significantly increased in group B (190.39 +/- 5.07, 0.048 +/- 0.002 and 0.143 +/- 0.011) as compared with A (124.81 +/- 4.01, 0.036 +/- 0.001 and 0.101 +/- 0.011) (P<0.05), but markedly decreased in group C (182.03 +/- 4.32, 0.044 +/ 0.001 and 0.126 +/- 0.007) in comparison with B (P<0.05). ICPmax /MAP was significantly lower in group B (36.82 +/- 5.47) than in A (59.99 +/- 5.69) (P<0.05), but remarkably higher in group C (51.1 +/- 5.63) than in B (P<0.05). CONCLUSION: Fasudil can improve erectile function in hypertensive rats by inhibiting the expression of RhoA / Rho kinase signaling and its possible attenuating effect on hypertension. PMID- 22295843 TI - [GLI-1 is involved in EGF-regulated enhancement of the invasiveness of prostate cancer ARCaP(E) cells in vitro]. AB - OBJECTIVE: To investigate the role of the hedgehog (HH) signaling pathway transcription factor glioma-associated oncogene hoinolog 1 (GLI-1) in EGF regulated enhancement of the invasiveness of the prostate cancer ARCaP(E) cell line in vitro. METHODS: The expressions of EGFR and GLI-1 in prostate cancer ARCaP(E) cells were analyzed by immunofluorescence staining. ARCaP(E) cells were treated with EGF at 100 ng/ml, followed by detection of the changes in cell morphology and invasiveness, as well as in the expressions of p-ERK, ERK and GLI 1. Migration transwell assay was used to determine the effects of 100 ng/ml EGF and GLI-1 antagonist GANT61 on the invasiveness of the ARCaP(E) cells. RESULTS: Both EGFR and GLI-1 were expressed in the ARCaP(E) cells. EGF induced morphological transition of epithelial-like ARCaP(E) cells to mesenchymal-like cells, increased their in vitro invasiveness, and significantly upregulated the expressions of p-ERK and GLI-1 in the ARCaP(E) cells (P<0.05). GANT61 significantly inhibited the in vitro invasiveness of the ARCaP(E) cells and reduced the enhancing effect of EGF on their invasiveness (P<0.05). CONCLUSION: The results from ARCaP(E) cells shed light on the cross-talk of the HH pathway with the EGF/ERK signaling pathway. GLI-1 might be responsible for EGF-regulated enhancement of the invasiveness of ARCaP(E) cells in vitro. PMID- 22295844 TI - [Over-expression of hypoxia-inducible factor-1alpha induces epithelial mesenchymal transition in LNCaP cells in vitro and in vivo]. AB - OBJECTIVE: To investigate the effects of the over-expression of hypoxia-inducible factor-1alpha (HIF-1alpha) on the epithelial-mesenchymal transition (EMT) and invasive potency of LNCaP cells in vitro and in vivo. METHODS: We cultured LNCaP cells stably expressing HIF-1alpha (LNCaP/HIF-1alpha) and LNCaP cells, identified the over-expression of HIF-1alpha, determined the proliferation of the two cell lines by MTT assay and the level of PSA in the supernatant of culture medium, and detected the anchorage independent growth by soft-agar colony formation assay. A subcutaneous tumor model was established in nude mice by injecting LNCaP/HIF 1alpha and LNCaP cells followed by observation of the tumor growth. Tumor specimens were obtained for immunohistochemistry. RESULTS: The over-expression of HIF-1alpha was confirmed in the LNCaP/HIF-1alpha cells by immunofluorescence staining and Western blotting. The level of PSA was obviously decreased in LNCaP/HIF-1alpha as compared with that in LNCaP cells. MTT assay identified the increased proliferation of LNCaP/HIF-1alpha cells. The cell colony forming ability of the LNCaP cells was significantly lower than that of the LNCaP/HIF 1alpha cells. The rate of tumorigenesis was increased and its time shortened in the LNCaP/HIF-1alpha group. Immunohistochemistry revealed an up-regulated expression of vimentin and a down-regulated expression of E-cadherin in the tumor specimens. CONCLUSION: The overexpression of HIF-1alpha can up-regulate the expression of vimentin and down-regulate the expression of E-cadherin, which may enhance the invasive potency of LNCaP cells by inducing EMT. PMID- 22295845 TI - [Differentially expressed proteins in the process of annexin 5 stimulating testosterone secretion from rat Leydig cells]. AB - OBJECTIVE: To study the differentially expressed proteins in the process of annexin 5 stimulating testosterone secretion in cultured rat Leydig cells. METHODS: Primary rat Leydig cells were cultured in vitro and treated with annexin 5 at the concentration of 1 nmol/L for 24 hours, and the cell proteins were extracted to be compared by two-dimensional gel electrophoresis (2-DE). The differentially expressed protein spots were selected to be analyzed by mass spectrometry. RESULTS: We obtained electrophoresis profiles with high resolution and reproducibility, found 50 differentially expressed protein spots, and identified 36 by mass spectrometry, of which 23 were overexpressed and 13 underexpressed in the Leydig cells treated with annexin 5. CONCLUSION: Differentially expressed protein profiles were established in the process of annexin 5 stimulating testosterone secretion in cultured rat Leydig cells, and identified the key role of these proteins in testosterone secretion. Our findings might be helpful to illuminate the mechanism of annexin 5 regulating testosterone secretion in rat Leydig cells. PMID- 22295846 TI - [Quantitative analysis by real-time elastosonography for the differential diagnosis of azoospermia: preliminary application]. AB - OBJECTIVE: To evaluate the quantitative analysis by real-time elastosonography in the differential diagnosis of obstructive azoospermia (OA) and non-obstructive azoospermia (NOA). METHODS: We evaluated the elastosonographic images of 200 cases of OA, 300 cases of NOA and 100 normal healthy controls, calculated the strain ratio of the testis to the scrotal skin and the median strain ratio among the three groups, and analyzed the best cut-off point for differentiating OA and NOA by the receiver operation characteristic (ROC) curve. RESULTS: The median strain ratio of NOA was 0.49 +/- 0.43, while that of OA was 0.35 +/- 0.31, with significant difference between the two groups (Z = - 19.173, P = 0.000 < 0.017). According to the results of ROC curve analysis, the area under the curve was 0.857 +/- 0.012 and the best cut-off point for differentiating OA and NOA was 0.395 (sensitivity = 84.5%, specificity = 74.5%, accuracy = 80.5%). CONCLUSION: Quantitative analysis by real-time elastosonography is a new valuable technique for the differential diagnosis of azoospermia. PMID- 22295847 TI - [Gene detection of Neisseria spp. isolated from male patients with genitourinary tract infections]. AB - OBJECTIVE: To detect the genes of Neisseria spp. isolated from patients with male genitourinary tract infections, and to study the pathogenicity of non-gonococcal strains of Neisseria and the laboratory diagnosis for the infections caused by Neisseria spp. METHODS: Using polymerase chain reaction and nucleotide sequencing, we amplified and sequenced 4 genes of Neisseria spp. isolated from patients with male genitourinary tract infections, including 16S rRNA, orfl, cppB and nspA. RESULTS: Fourteen Neisseria strains were identified through analysis of the 16S rRNA gene, including 3 N. mucosa strains, 3 N. cinerea strains, 2 N. gonorrhoea strains, 2 N. sicca strains, 2 N. subflava strains, 1 N. lactamica strain, and 1 N. polysaccharea strain. Among them, 9 showed positive results in gonococcal fluorescence-labeled multiplex-PCR detection, 1 in cppB gene reaction, 5 in orfl gene reaction, and 3 in nspA gene reaction. The consistency rate was 85.7% between the above results from our gene detection and those from the routine bacteriological methods. CONCLUSION: The cppB gene is absent in the non gonococcal strains of Neisseria spp. that can cause male genitourinary tract infection. Most of the strains not only lack virulence-associated orfl and nspA genes, but also show positive results in gonococcal fluorescence-labeled multiplex-PCR detection, which is one of the important reasons for the misdiagnosis and missed diagnosis of gonorrhea infection. The combination of routine bacteriological methods and gene detection in laboratory examinations may help improve the accuracy rates of Neisseria species identification and clinical diagnosis of the infections caused by Neisseria spp. PMID- 22295848 TI - [Erectile dysfunction in men with high-normal blood pressure]. AB - OBJECTIVE: To investigate the prevalence of erectile dysfunction (ED) in men with high-normal blood pressure (HNBP). METHODS: This study included 120 men with HNBP and another 120 with normal blood pressure (NBP) as controls. We analyzed the scores of the two groups on the International Index of Erectile Dysfunction 5 (IIEF-5). RESULTS: The ED prevalence in the men with HNBP was 25.8%. After controlling for age, nationality, occupation, education, income, smoking, alcohol consumption, exercise, obesity, fatty liver, blood lipids, blood glucose, and blood uric acid, the incidence of ED was 25.8% in the HNBP group, significantly higher than 14.2% in the NBP group (P<0.05). CONCLUSION: The prevalence of ED is higher in men with HNBP than in those with NBP. PMID- 22295849 TI - [Correlation of testicular volume and reproductive hormone level with the results of testicular sperm aspiration in non-obstructive azoospermia patients]. AB - OBJECTIVE: To investigate the correlation of the testis volume and reproductive hormone level with the results of testicular sperm aspiration (TESA) in non obstructive azoospermia (NOA) patients, and to explore the cut-off value of the testis volume and reproductive hormone level in predicting the results of TESA so as to provide reliable information for the diagnosis and treatment of NOA. METHODS: We enlisted 121 NOA patients in this study, divided them into a sperm group and a non-sperm group based on the results of TESA, and measured their testis volumes and reproductive hormone levels. RESULTS: The left testis volume, the right testis volume, and the levels of prolactin (PRL), follicle-stimulating hormone (FSH), luteinising hormone (LH), estradiol (E2) and total testosterone (T) in the non-sperm and sperm groups were (7.07 +/- 1.06) ml vs (11.75 +/- 1.38) ml, (7.37 +/- 1.37) ml vs (11.70 +/- 1.98) ml, (12.43 +/- 11.69) ng/ml vs (9.60 +/- 4.55) ng/ml, (15.77 +/- 10.84) mIU/ml vs (8.01 +/- 7.43) mIU/ml, (6.12 +/- 2.92) mIU/ml vs (8.11 +/- 20.11) mIU/ml, (119.36 +/- 43.52) pmol/L vs (141.12 +/- 48.33) pmol/L, and (11.43 +/- 4.05) nmol/L vs (12.46 +/- 4.60) nmol/L, respectively. The mean levels of serum FSH and PRL were significantly higher in the non-sperm than in the sperm group. Although the mean testis volume of the former was less than that of the latter, there were no significant differences between the two groups, and nor were any significant differences in age and the levels of E2 and T. The cut-off value of the testis volume was 9 ml, with sensitivity of 93.8%/89.6% (left/right) and specificity of 100%/94.3% (left/right). The area under curve (AUC) of the left testis volume was 0.984 and that of the right was 0.961, indicating a high diagnostic accuracy. The cut-off value of the serum FSH level was 8.18 mIU/ml, with a sensitivity of 71.2% and a specificity of 75.0%. The AUC of the FSH level was 0.743, suggestive of a moderate diagnostic accuracy. CONCLUSION: The testis volume and FSH level are important for predicting the TESA results of NOA patients, and the former has even a higher diagnostic accuracy than the latter. PMID- 22295850 TI - [Male genitourinary system lymphoma: a clinicopathological analysis]. AB - OBJECTIVE: To investigate the clinicopathological features and immunophenotypes of male genitourinary system lymphoma. METHODS: We retrospectively studied the histopathological characteristics and immunohistochemical markers of 35 cases of male genitourinary system lymphoma, and reviewed the relevant literature. RESULTS: The 35 patients of male genitourinary system lymphoma were aged from 4 to 83 (mean 56.5) years, 28 (80%) of them > or = 50 years. Twenty-eight cases (80%) involved the testis, 3 (8.6%) the prostate, 1 (2.9%) the spermatic cord, 1 the seminal vesicles, 1 the penis and 1 the epididymis. Histologically, 22 cases (62.9%) were diffused large B cell lymphoma (DLBCL), 6 (17.1%) mucosa associated lymphoid tissue (MALT) lymphoma, 4 (11.4%) Burkitt lymphoma, 2 (5.7%) peripheral T cell lymphoma, and 1 (2.9%) plasmacytoma. CONCLUSION: Male genitourinary system lymphomas are rare tumors clinically, which occur more often in the elderly. The majority of them are B cell lymphomas, of which the most common is DLBCL, followed by MALT lymphoma and Burkitt lymphoma. T cell lymphoma and plasmacytoma are rare. The diagnosis of male genitourinary system lymphoma relies on the histopathology, and immunohistochemical markers are of high value for its definite diagnosis, classification and differential diagnosis. PMID- 22295851 TI - [Effects of opioid analgesics on sperm motility in vitro]. AB - OBJECTIVE: To observe the effects of short-term exposure to opioid analgesics on human sperm motility. METHODS: Twenty normal semen samples were collected, each divided into 19 groups, one as the control and the others treated in vitro with six opioid analgesics at three different concentrations, respectively, and sperm motility was assessed by computer-assisted sperm analysis at 15 min, 2 h and 4 h. RESULTS: Compared with the control group, fentanyl, alfentanil and sufentanil at 1 x 10(-5), 2 x 10(-3) and 0.05 mg/ml significantly decreased the percentage of grade a + b sperm at 15 min, 2 h and 4 h (P<0.05), and so did butorphanol at 2 x 10(-3) and 0.05 mg/ml (P<0.05) and dezocine at 0.05 and 0.5 mg/ml (P<0.05), but neither showed any remarkable effect at 1 x 10(-5) mg/ml at the three time points (P>0.05). Pentazocine effected no significant difference at 3 x 10(-5) and 0. 05 mg/ml (P>0.05) but a gradual increase in the percentage of grade a + b sperm at 0.5 mg/ml at the three time points (P<0.05). Butorphanol totally inhibited sperm motility at 0.05 mg/ml at 15 min and at 2 x 10(-3) mg/ml at 2 h, and so did dezocine at 0.05 and 0.5 mg/ml, but such inhibitory effect was not observed with fentanil, alfentanil and sulfentanil at 0.05 mg/ml. As for the sperm motility decreasing effect at 0.05 mg/ml at 15 min, sufentanil, butorphanol and dezocine exhibited significant differences (P<0.05) while fentanyl displayed none from alfentanil (P>0.05). CONCLUSION: Given the same length of time of treatment, butorphanol and dezocine totally inhibit sperm motility at a high concentration, but make no significant change at a low concentration. While fentanyl, alfentanil and sufentanil can significantly decrease sperm motility at the same low concentration, and partially inhibit it at all concentrations. On the contrary, a high concentration of pentazocine can promote human sperm motility. PMID- 22295852 TI - [Expression of macrophage inflammatory protein-1alpha in EPS and its significance]. AB - OBJECTIVE: To detect the mRNA and protein expressions of MIP-1alpha in EPS and determine their significance in the sub-typing of chronic prostatitis. METHODS: We collected samples of expressed prostatic secretion (EPS) from 50 cases of chronic prostatitis, including 16 cases of chronic bacterial prostatitis (CBP), 23 cases of chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CPPS) (11 CPPS IIIA, 12 CPPS IIIB), and 11 cases of type-IV asymptomatic inflammatory prostatitis (AIP). Another 15 healthy volunteers were included as normal controls. The mRNA and protein levels of MIP-1alpha in EPS were determined by RT PCR and ELISA, respectively, followed by statistical analysis with SPSS 15.0. RESULTS: The mRNA expression of MIP-1alpha was markedly higher in the CPPS IIIA and CPPS IIIB groups than in the others (P<0.05). The protein level of MIP-1alpha was (1174.3 +/- 89.2) pg/ml in CPPS IIIA and (842.3 +/- 76.2) pg/ml in CPPS IIIB, significantly higher than (198.0 +/- 37.8) pg/ml in the control, (347.0 +/- 61.6) pg/ml in CBP and (292.0 +/- 56.4) pg/ml in type-IV AIP (P<0.05). CONCLUSION: Determination of mRNA and protein levels of MIP-1alpha in EPS may help the sub typing and diagnosis of chronic prostatitis. PMID- 22295853 TI - [Testosterone level not significantly correlates to endothelial progenitor cells in Klinefelter's syndrome patients]. AB - OBJECTIVE: To explore the correlation of the testosterone level with circulated endothelial progenitor cells in patients with Klinefelter's syndrome (KS) and its clinical significance. METHODS: This study included 36 patients affected by non mosaic 47, XXY KS, each with one or more cardiovascular risk factors. Serum hormone levels and the content of circulated endothelial progenitor cells were determined by radioimmunology and cell culture methods, respectively, and the measurement was repeated after 6 months of testosterone replacement therapy. RESULTS: After testosterone replacement therapy, the testosterone level was increased from (8 +/- 3) to (24 +/- 10) nmol/L, while the content of endothelial progenitor cells ([41 +/- 48] cells/ml) showed no significant rise. CONCLUSION: There is no obvious correlation between the testosterone level and the content of endothelial progenitor cells in KS patients. PMID- 22295854 TI - [Magnetic activated cell sorting and its application in the studies of male infertility]. AB - Magnetic activated cell sorting (MACS) is considered as a flexible, fast, specific and simple cell sorting system that can separate target cells effectively according to specific markers on the cell surface, for which it has won a wide clinical application. MACS offers a new platform for male infertility research, as well as a novel idea for applying this technology in the optimization of semen quality and the isolation of germ cells. This article briefly introduces the basic principles of MACS, and summaries its present and potential clinical application in male infertility research, as in spermatozoa selection and cryopreservation, and the isolation of spermatogonial stem cells and germ cells. PMID- 22295855 TI - [Spermicidal effect of alcohol extracts from different ratios of Sophora flavescens Ait/Chinese Bulbul in vitro]. AB - OBJECTIVE: To observe the spermicidal effect of alcohol extracts from different ratios of Sophora flavescens Ait/Chinese Bulbul in vitro. METHODS: Semen samples aseptically obtained by masturbation and prepared by density gradient centrifugation from 15 healthy men were incubated in the alcohol extracts from 9 different ratios of Sophora flavescens Ait/Chinese Bulbul for 20 seconds, 2 minutes and 4 minutes. Then the motility and movement parameters of the sperm were detected by computer-assisted semen analysis, and the minimal effective concentrations of the instant spermicidal effect of the extracts were determined. RESULTS: At the ratio of 3:1, the extract at 0.5 mg/ml significantly inhibited the sperm motility and other sperm movement parameters VCL, VSL, VAP, ALH, WOB and MAD, as compared with the control group. The minimal effective concentration of the instant spermicidal effect of the extracts was 3.5 mg/ml at 3:1. CONCLUSION: The alcohol extracts from Sophora flavescens Ait and Chinese Bulbul at the ratio of 3:1 have the best spermicidal effect in vitro. PMID- 22295856 TI - [Protective effect of lycium barbarum polysaccharides against heat stress-induced germ cell apoptosis in rats and its mechanism]. AB - OBJECTIVE: To investigate the protective effect of lycium barbarum polysaccharides (LBP) against heat stress-induced apoptosis of germ cells in rats and its action mechanism. METHODS: Ninety male Sprague-Dawley rats were randomly divided into five groups of 18 each: control, heat stress (HS), high-dose LBP, median-dose LBP and low-dose LBP. The rats of the three LBP groups were given LBP by intragastric administration at 100 mg/(kg x d), 50 mg/(kg x d) and 10 mg/(kg x d) respectively for 14 days, and on the 15th day they, together with those of the HS group, were exposed to a heat of 43 degrees C for 30 minutes. At 24 h, 48 h and 7 d after heat stress, the animals were killed by cervical dislocation, followed by observation of the apoptotic germ cells by TUNEL, determination of the expression of Caspase-3 by immunohistochemistry and detection of cytochrome C in the cytosol by ELISA. RESULTS: Compared with the HS group, the three LBP groups showed statistically significant decreases in the apoptosis index (P<0.05), the expression level of Caspase-3 in germ cells (P<0.05) and the concentration of cytochrome C in the cytosol (P<0.05). CONCLUSION: LBP can inhibit cytochrome C release from mitochondria, decrease the expression of Caspase-3 and hence reduce the apoptosis of germ cells. It thus can be deduced that LBP can protect germ cells against apoptosis via the mitochondrial pathway. PMID- 22295857 TI - [Alternate-day oral tadalafil for erectile dysfunction with no successful intercourse at the baseline]. AB - OBJECTIVE: To summarize the experience in the treatment of erectile dysfunction (ED) with no successful intercourse at the baseline with tadalafil. METHODS: We retrospectively analyzed 21 cases of ED with no successful intercourse at the baseline treated with tadalafil on alternate days combined with sex guidance. RESULTS: After 4 weeks of tadalafil treatment, 19 of the patients achieved successful sexual intercourse, and the IIEF-5 score was remarkably improved as compared with pre-medication (3.24 +/- 1.55 vs 18.95 +/- 3.02, P<0.0001). Mild adverse reactions were observed in 6 cases, including 2 cases of mild headache and 4 cases of facial blush. CONCLUSION: Tadalafil on alternate days combined with sex guidance can significantly improve ED with no successful intercourse at the baseline. PMID- 22295858 TI - Deletion of chromosome 20 in bone marrow of patients with Shwachman-Diamond syndrome, loss of the EIF6 gene and benign prognosis. PMID- 22295859 TI - The complete mitochondrial genome of the loggerhead turtle Caretta caretta (Testudines: Cheloniidae): genome description and phylogenetic considerations. AB - The marine turtle Caretta caretta is a widely distributed species that is facing critical population decline, especially in the Mediterranean rookeries. Molecular markers, such as mitochondrial DNA (mtDNA) sequences, are of great importance for the description and monitoring of turtle migratory populations. The complete sequence of the C. caretta mitochondrial genome is presented here. The genome comprises 16,440 base pairs, containing 37 genes (13 protein-coding genes, 22 tRNA genes, and 2 rRNA genes), and a control region, all organized similar to the majority of vertebrate mitogenomes. MtDNA length polymorphism and heteroplasmy were observed among, and within, individuals due to the variable size of a microsatellite repeat residing at the 3' end of the control region. The use of the above repeat as a marker for individual fingerprinting is discussed. Furthermore, phylogenetic analyses among Testudines based on complete mitogenomes, as well as among marine turtles based on partial mtDNA sequences, are considered. PMID- 22295860 TI - Mitochondrial origin of the matrilocal Mosuo people in China. AB - The Mosuo people are currently the only matrilocal population in China. The origins of the population and their matrilocal tradition remain unknown. To address these questions, we studied the mitochondrial DNA (mtDNA) diversity of the Mosuo. Lower mtDNA diversity is expected in matrilocal populations because the women remain with their families after marriage, and there is generally less movement of mtDNA genomes in matrilocal populations. However, the haplotype diversity of this population is not lower than the neighboring patrilocal populations, indicating that the Mosuo started practicing matrilocality at least after the Paleolithic Age. A previous haplogroup frequency clustering study indicated that the Mosuo are closest to the Naxi people, but the network analysis of individual sequence haplotypes presented herein shows that most Mosuo lineages cluster with Pumi lineages. Therefore, we concluded that the Mosuo people have the closest genetic relationship with the Pumi, and that they started to practice matrilocality several thousand years ago. PMID- 22295861 TI - Molecular identification of three Ompok species using mitochondrial COI gene. AB - A DNA-based barcode identification system that is applicable to all animal species will provide a simple, universal tool for the identification of fish species. The barcode system is based on sequence diversity in subunit 1 cytochrome c oxidase (COI) gene. Identification and characterization of fish species based on morphological characters are sometimes found to be erroneous and environmentally affected. There are no studies on the genus Ompok in India at molecular level and species identification of the Ompok is usually carried out through morphological features. A total of 106 samples from three species Ompok pabda, O. pabo and O. bimaculatus were collected from eight sampling sites of seven Indian rivers. One hundred and six sequences were generated from COI region of three Ompok species and 21 haplotypes were observed. The sequence analysis of COI gene revealed three genetically distinct Ompok species and exhibited identical phylogenetic resolution among them. The partial COI gene sequence can be used as a diagnostic molecular marker for identification and resolution of taxonomic ambiguity of Ompok species. PMID- 22295862 TI - Complete mitochondrial genome of the Antarctic amphipod Gondogeneia antarctica (Crustacea, amphipod). AB - The complete sequence of the mitochondrial genome of the Antarctic amphipod Gondogeneia antarctica was determined to be 18,424 bp in length, and to contain 13 protein-coding genes (PCGs), 22 tRNA genes, and large (rrnL) and small (rrnS) rRNA genes. Its total A+T content is 70.1%. The G. antarctica mitogenome is the largest known among those of crustaceans, due to the existence of two relatively large intergenic non-coding sequences. The PCG arrangement of G. antarctica is identical to that of the ancestral pancrustacean ground pattern, although the tRNA arrangement differs somewhat. The complete mitogenome sequences of 68 species of pancrustacea have been added to the NCBI database, only 4 of which represent complete mitogenome sequences from amphipods. This is the first report of a mitogenome sequence of an Antarctic amphipod, and provides insights into the evolution of crustacean mitochondrial genomes, particularly in amphipods. PMID- 22295863 TI - Complete mitochondrial genome of the northern mauxia shrimp Acetes chinensis (Decapoda, Dendrobranchiata, Sergestoidae). AB - Here, we report the first complete mitochondrial genome sequence of northern mauxia shrimp Acetes chinensis (Decapoda, Dendrobranchiata, Sergestoidae). The genome sequence was 15,740 bp in size, and the gene content, gene order and transcriptional polarity were almost identical to the pancrustacean ground pattern, with the one exception that an extra trnS(1)(AGC) was adjacent to the original trnS(1)(AGA). The two tandemly duplicated trnS(1) showed a high sequence similarity (82.3%), with almost identical secondary structure lacking a DHU arm. Comparison of codon usage suggests that both of the trnS(1) genes were functional. PMID- 22295864 TI - Complete mitochondrial genome of the mudskipper Boleophthalmus pectinirostris (Perciformes, Gobiidae): repetitive sequences in the control region. AB - The mudskipper, Boleophthalmus pectinirostris (Perciformes, Gobiidae), is an amphibious gobioid fish. In this paper, the complete mitochondrial genome of B. pectinirostris was firstly determined. The mitogenome (17,111 bp) comprises 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 1 putative control region. 130-bp tandem repeat was identified in the control region, which was almost identical among the 10 individuals examined, and three different frequencies of the repeat unit (five, six or seven) were found among these individuals. PMID- 22295865 TI - The complete mitochondrial genome of the spotted steed, Hemibarbus maculatus (Teleostei, Cypriniformes). AB - The complete mitogenome sequence of the spotted steed (Hemibarbus maculatus) was determined using long PCR reactions. The genome is 16,611 bp long and consists of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and a control region. The gene order and composition of H. maculatus was similar to that of most other vertebrates. The base composition of H-strand in descending order is A (29.16%), C (27.41%), T (25.93%), and G (17.50%), with an AT content of 55.09%. The Kimura two-parameter distances between mitogenome sequences of H. maculatus and Hemibarbus labeo, Hemibarbus barbus, Hemibarbus longirostris, Hemibarbus mylodon were 2.09%, 2.35%, 12.77%, and 13.92%, respectively. The phylogenetic relationships among the five Hemibarbus species based on the whole mitogenome sequence data were (((H. barbus, H. labeo), H. maculatus), (H. longirostris, H. mylodon)). PMID- 22295866 TI - Complete mitochondrial genome of the Manis pentadactyla (Pholidota, Manidae): comparison of M. pentadactyla and M. tetradactyla. AB - In this paper, we sequenced the complete mitochondrial genome of the Manis pentadactyla (Pholidota: Manidae), which is considered as an endemic species in China. It is listed as a vulnerable species by the International Union for Conservation of Nature and Natural Resources Red List and also an endangered species in China. The genome is 16,578 bp in size. Its gene arrangement pattern was identical with those of Manis tetradactyla. We compared the mitochondrial genome of M. pentadactyla with that of the M. tetradactyla. Nucleotide sequence similarity between the two whole mitochondrial genomes was 79.30%, and the relatively low similarity seems to indicate that the two species are distinctly separated on the species level. The information on the mitochondrial genome comparison of the two species was discussed in detail in this paper. PMID- 22295867 TI - Mitochondrial genome of the cockscomb pearl mussel Cristaria plicata (Bivalvia, Unionoida, Unionidae). AB - The complete mitochondrial genome sequence of the cockscomb pearl mussel Cristaria plicata, which is an endangered species in South Korea, was sequenced. The circle genome (15,708 bp in size) consists of 13 protein-coding genes, 2 rRNA genes, and 22 tRNA genes. There were 26 noncoding regions (NCs) found throughout the mitogenome of C. plicata, ranging in size from 2 to 327 bp, and the two largest NC regions, NC286 and NC326, were found between ND5 and tRNA(Gln) (286 bp) and between tRNA(Glu) and ND2 (326 bp), respectively. The 13 mitochondrial protein-coding genes of a female individual of C. plicata collected from Korea (15,708 bp) were compared to those of the Chinese individual (15,712 bp) published before. The result showed that ND3 is the most conserved with 100% nucleotide similarity, and each of the other protein-coding genes has ca. 99%, respectively. The two largest NCs among 26 NCs have totally 98% nucleotide similarity between Korean and Chinese ones. PMID- 22295868 TI - Lipase immobilization on differently functionalized vinyl-based amphiphilic polymers: influence of phase segregation on the enzyme hydrolytic activity. AB - Microbial lipase from Candida rugosa was immobilized by physical adsorption onto an ethylene-vinyl alcohol polymer (EVAL) functionalized with acyl chlorides. To evaluate the influence of the reagent chain-length on the amount and activity of immobilized lipase, three differently long aliphatic fatty acids were employed (C8, C12, C18), obtaining EVAL functionalization degrees ranging from 5% to 65%. The enzyme-polymer affinity increased with both the length of the alkyl chain and the matrix hydrophobicity. In particular, the esterified polymers showed a tendency to give segregated hydrophilic and hydrophobic domains. It was observed the formation of an enzyme multilayer at both low and high protein concentrations. Desorption experiments showed that Candida rugosa lipase may be adsorbed in a closed form on the polymer hydrophilic domains and in an open, active structure on the hydrophobic ones. The best results were found for the EVAL-C18 13% matrix that showed hyperactivation with both the soluble and unsoluble substrate after enzyme desorption. In addition, this supported biocatalyst retained its activity for repetitive cycles. PMID- 22295869 TI - Evaluation of levetiracetam as adjunctive treatment for refractory canine epilepsy: a randomized, placebo-controlled, crossover trial. AB - BACKGROUND: There is little evidence-based information available to guide treatment of refractory epilepsy in dogs. The antiepileptic drug levetiracetam (LEV) is administered to dogs, although its safety and efficacy are unknown. OBJECTIVE: To evaluate the safety and efficacy of LEV as adjunctive therapy for refractory epilepsy in dogs. ANIMALS: Thirty-four client-owned dogs with idiopathic epilepsy. METHODS: Randomized, blinded trial involving dogs resistant to phenobarbital and bromide. Dogs received LEV (20 mg/kg PO q8h) or placebo for 16 weeks, and after a 4-week washout were crossed over to the alternate treatment for 16 weeks. Owners kept records on seizure frequency and adverse events. Hemogram, chemistry profile, urinalysis, and serum antiepileptic drug concentrations were evaluated at established intervals. RESULTS: Twenty-two (65%) dogs completed the study. Weekly seizure frequency during the 1st treatment period decreased significantly during LEV administration relative to baseline (1.9 +/- 1.9 to 1.1 +/- 1.3, P = .015). The reduction in seizures with LEV was not significant when compared to placebo (1.1 +/- 1.3 versus 1.5 +/- 1.7, P = .310). The most common adverse event was ataxia, with no difference in incidence between LEV and placebo (45 versus 18%, P = .090). No changes in laboratory parameters were identified and owners reported an improved quality of life (QOL) with LEV compared to placebo (QOL score 32.7 +/- 4.3 versus 29.4 +/- 4.5, P = .028). CONCLUSIONS AND CLINICAL IMPORTANCE: Adjunctive treatment with LEV appears safe in epileptic dogs. Efficacy of LEV over placebo was not demonstrated, although the power of the study was limited. Further evaluation of LEV as treatment for epilepsy in dogs is warranted. PMID- 22295870 TI - The Size 1 ProSealTM laryngeal mask airway in infants: a randomized, noncrossover study with the ClassicTM laryngeal mask airway. AB - BACKGROUND: In recent years, numerous scientific publications have endorsed the superiority of the ProSealTM laryngeal mask airway (PLMA) over the ClassicTM laryngeal mask airway (cLMA) in adults, children, and infants. The PLMA forms a better seal for both the respiratory and gastrointestinal tracts, provides easier access to the gastrointestinal tract, and exerts lower mucosal pressures for a given seal pressure. This study aims to determine whether this superiority can also be observed for the size 1 PLMA used in anesthetized neonates and infants with positive pressure ventilation. METHODS: Sixty consecutive neonates and infants undergoing elective surgical procedures were randomized to airway management with the size 1 PLMA or cLMA. For all patients, we recorded ease of insertion, effective airway time, number of placement attempts, oropharyngeal leak pressure, fiberoptic position, audible leaks, mask displacement, number of reinsertions during maintenance, gastric insufflation, and frequency of blood stain. RESULTS: Ease of insertion, successful insertion in <3 attempts, fiberoptic position of the airway tube, and frequency of blood stain were similar in both groups. Effective airway time was lower for the PLMA group (30.5 vs 35.6 s). Oropharyngeal leak pressure was higher with the PLMA (32.9 vs 22.2 cm H(2)O, P < 0.001) and gastric insufflation less common (0% vs 6%, P = 0.492). There were fewer mask displacements during maintenance of anesthesia with the PLMA (0% vs 26.7%, P < 0.001). Mask reinsertion was not necessary during maintenance of anesthesia with the PLMA, although it was necessary in 14 cases in the cLMA group (0% vs 46%, P < 0.001). Audible leaks were less common with the PLMA (0% vs 46%, P < 0.001). CONCLUSIONS: We conclude that the size 1 PLMA is a stable, safe, and efficacious airway control device during neonatal and infant anesthesia, allowing higher peak airway pressure during positive pressure ventilation, with fewer mask displacements and gastric insufflations than the cLMA. PMID- 22295871 TI - Caspase-1 inhibitors from an extremophilic fungus that target specific leukemia cell lines. AB - Berkeley Pit Lake, Butte, Montana, is a 540 m deep abandoned open-pit copper mine filled with over 140 billion liters of acidic, metal-sulfate-contaminated water. This harsh environment has yielded several microorganisms that produce interesting biologically active compounds. Several polyketide metabolites including the new berkazaphilones A (1) and B (2) and octadienoic acid derivatives berkedienoic acid (13) and berkedienolactone (15), as well as previously reported azaphilone 4, vermistatin (6), dihydrovermistatin (7), penisimplicissin (8), aldehyde 9, and methylparaconic acid (11), were isolated from a culture broth of Penicillium rubrum taken from a depth of 270 m. The structures of these compounds were deduced by interpretation of spectroscopic data. The compounds were isolated either for their inhibition of the signal transduction enzyme caspase-1 or because of their structural similarity to these inhibitors. Selected compounds were further evaluated for their ability to inhibit interleukin-1beta production by inflammasomes in induced THP-1 cells. Berkazaphilones B (2) and C (4) and vermistatin analogue penisimplicissin (8) exhibited selective activity against leukemia cancer cell lines in the National Cancer Institute 60 human cell line assay. PMID- 22295872 TI - Computed tomography scans before surgery for thyroid cancer. PMID- 22295876 TI - Model-based treatment optimization of a novel VEGFR inhibitor. AB - AIM: To evaluate dosing and intervention strategies for the phase II programme of a VEGF receptor inhibitor using PK-PD modelling and simulation, with the aim of maximizing (i) the number of patients on treatment and (ii) the average dose level during treatment. METHODS: A previously developed PK-PD model for lenvatinib (E7080) was updated and parameters were re-estimated (141 patients, once daily and twice daily regimens). Treatment of lenvatinib was simulated for 16 weeks, initiated at 25 mg once daily. Outcome measures included the number of patients on treatment and overall drug exposure. A hypertension intervention design proposed for phase II studies was evaluated, including antihypertensive treatment and dose de-escalation. Additionally, a within-patient dose escalation was investigated, titrating up to 50 mg once daily unless unacceptable toxicity occurred. RESULTS: Using the proposed antihypertension intervention design, 82% of patients could remain on treatment, and the mean dose administered was 21.5 mg day-1. The adverse event (AE) guided dose titration increased the average dose by 4.6 mg day-1, while only marginally increasing the percentage of patients dropping out due to toxicity (from 18% to 20.8%). CONCLUSIONS: The proposed hypertension intervention design is expected to be effective in maintaining patients on treatment with lenvatinib. The AE-guided dose titration with blood pressure as a biomarker yielded a higher overall dose level, without relevant increases in toxicity. Since increased exposure to lenvatinib seems correlated with increased treatment efficacy, the adaptive treatment design may thus be a valid approach to improve treatment outcome. PMID- 22295877 TI - Outcome of hepatectomy in super-elderly patients with hepatocellular carcinoma. AB - AIM: The aim of this study was to investigate the characteristics of super elderly hepatocellular carcinoma (HCC) patients aged 80 years or more who underwent hepatectomy and to clarify whether elderly patients with HCC benefit from hepatectomy. METHODS: Between March 1992 and December 2008, 278 patients who underwent curative hepatectomy for HCC were investigated. Super-elderly patients were defined as those aged 80 years or more. Clinicopathological data and outcomes after hepatectomy were compared between super-elderly and non-super elderly groups. RESULTS: Preoperative parameters, such as biochemical examinations, and liver function tests in the non-super-elderly group were comparable with those of the super-elderly group (n = 11). Exceptionally, albumin level in the super-elderly group was lower than that in the non-super-elderly group (P = 0.03). Surgical data and the prevalence of postoperative complications did not differ significantly between the two groups. No mortality was observed in the super-elderly and non-super-elderly group. CONCLUSIONS: Hepatectomy for HCC was a feasible option even in super elderly patients aged 80 years or older with accurate selection. PMID- 22295879 TI - Proteomics of post-traumatic proliferative vitreoretinopathy in rabbit retina reveals alterations to a variety of functional proteins. AB - PURPOSE: The purpose of this study was to investigate the protein profiles and pathogenesis in rabbit retinas from normal and post-traumatic proliferative vitreoretinopathy (PVR). MATERIALS AND METHODS: A modified rabbit model of post traumatic PVR was modified used in the study. Two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry (MS) were utilized to identify the changes to the protein profiles of rabbit retina. The myosin light chains-2 (MLC2) was subsequently chosen as a target for its biggest difference in 2-DE gels using Western blot, immunohistochemistry and MTT assay. RESULTS: Comparative gel analysis revealed that 20 spots were up-regulated or novel emerged and 12 were down-regulated or even disappeared in PVR retinas. The majority of changes could consist of the following functional groups of proteins including the cell skeleton proteins; the wound healing/cell adhesion proteins; the proteins involved in metabolism and in blood-retina barrier destruction; oxidative stress related proteins and the ion channel proteins. Western blot analysis confirmed that MLC2 protein expression was upregulated in PVR retinas. MTT assay showed that the anti-MLC2 monoclonal antibody significantly decreased the proliferation in ARPE-19 cells stimulated with different concentrations and times in vitro experiment. CONCLUSIONS: Our results suggested that PVR is a complicated pathology process with alterations in expression of a variety of functional proteins rather than a single key protein. The data reported may be useful for further studies on pathogenesis of human PVR and for the screening of biomarkers to develop new potential therapeutic approaches. PMID- 22295878 TI - Ligand and antagonist driven regulation of the Vibrio cholerae quorum-sensing receptor CqsS. AB - Quorum sensing, a bacterial cell-cell communication process, controls biofilm formation and virulence factor production in Vibrio cholerae, a human pathogen that causes the disease cholera. The major V. cholerae autoinducer is (S)-3 hydroxytridecan-4-one (CAI-1). A membrane bound two-component sensor histidine kinase called CqsS detects CAI-1, and the CqsS -> LuxU -> LuxO phosphorelay cascade transduces the information encoded in CAI-1 into the cell. Because the CAI-1 ligand is known and because the signalling circuit is simple, consisting of only three proteins, this system is ideal for analysing ligand regulation of a sensor histidine kinase. Here we reconstitute the CqsS -> LuxU -> LuxO phosphorylation cascade in vitro. We find that CAI-1 inhibits the initial auto phosphorylation of CqsS whereas subsequent phosphotransfer steps and CqsS phosphatase activity are not CAI-1-controlled. CAI-1 binding to CqsS causes a conformational change that renders His194 in CqsS inaccessible to the CqsS catalytic domain. CqsS mutants with altered ligand detection specificities are faithfully controlled by their corresponding modified ligands in vitro. Likewise, pairing of agonists and antagonists allows in vitro assessment of their opposing activities. Our data are consistent with a two-state model for ligand control of histidine kinases. PMID- 22295880 TI - Arsenic speciation and volatilization from flooded paddy soils amended with different organic matters. AB - Arsenic (As) methylation and volatilization in soil can be increased after organic matter (OM) amendment, though the factors influencing this are poorly understood. Herein we investigate how amended OM influences As speciation as well as how it alters microbial processes in soil and soil solution during As volatilization. Microcosm experiments were conducted on predried and fresh As contaminated paddy soils to investigate microbial mediated As speciation and volatilization under different OM amendment conditions. These experiments indicated that the microbes attached to OM did not significantly influence As volatilization. The arsine flux from the treatment amended with 10% clover (clover-amended treatment, CT) and dried distillers grain (DDG) (DDG-amended treatment, DT2) were significantly higher than the control. Trimethylarsine (TMAs) was the dominant species in arsine derived from CT, whereas the primary arsine species from DT2 was TMAs and arsine (AsH(3)), followed by monomethylarsine (MeAsH(2)). The predominant As species in the soil solutions of CT and DT2 were dimethylarsinic acid (DMAA) and As(V), respectively. OM addition increased the activities of arsenite-oxidizing bacteria (harboring aroA-like genes), though they did not increase or even decrease the abundance of arsenite oxidizers. In contrast, the abundance of arsenate reducers (carrying the arsC gene) was increased by OM amendment; however, significant enhancement of activity of arsenate reducers was observed only in CT. Our results demonstrate that OM addition significantly increased As methylation and volatilization from the investigated paddy soil. The physiologically active bacteria capable of oxidization, reduction, and methylation of As coexisted and mediated the As speciation in soil and soil solution. PMID- 22295882 TI - Trapping of an intermediate in the reaction catalyzed by flavin-dependent thymidylate synthase. AB - Thymidylate is a DNA nucleotide that is essential to all organisms and is synthesized by the enzyme thymidylate synthase (TSase). Several human pathogens rely on an alternative flavin-dependent thymidylate synthase (FDTS), which differs from the human TSase both in structure and molecular mechanism. It has recently been shown that FDTS catalysis does not rely on an enzymatic nucleophile and that the proposed reaction intermediates are not covalently bound to the enzyme during catalysis, an important distinction from the human TSase. Here we report the chemical trapping, isolation, and identification of a derivative of such an intermediate in the FDTS-catalyzed reaction. The chemically modified reaction intermediate is consistent with currently proposed FDTS mechanisms that do not involve an enzymatic nucleophile, and it has never been observed during any other TSase reaction. These findings establish the timing of the methylene transfer during FDTS catalysis. The presented methodology provides an important experimental tool for further studies of FDTS, which may assist efforts directed toward the rational design of inhibitors as leads for future antibiotics. PMID- 22295883 TI - Very early initiation of statin therapy and mortality in patients with acute coronary syndrome. AB - BACKGROUND: Current guidelines for the treatment of patients with acute coronary syndrome (ACS) recommend the use of statins before hospital discharge. However, the prognostic impact of an early initiation of treatment is uncertain. METHODS: We reviewed data from randomized controlled trials (RCTs) to test the hypothesis that differences in the time of initiation of statin therapy may be associated with differences in mortality after hospitalization for ACS. We extracted data from 10 RCTs which evaluated one-month mortality of patients early treated with statins (mean time of administration<=72 h from hospitalization) compared to patients receiving placebo or standard care. RESULTS: Overall, 4030 patients were randomized to statin therapy and 4022 patients to the control group. The effect of statins on mortality was not significant (OR 0.81, 95% CI: 0.58-1.12; P=0.198). The 10 trials were divided up by the mean time of initiation of statin therapy (day 1, day 2 and day 3). Statins reduced mortality when treatment was initiated in day 1 (OR 0.63, 95% CI: 0.41-0.99; P=0.045), not in day 2 or day 3. There was no statistically significant interaction across the subgroups in the risk of mortality (P=0.303). CONCLUSIONS: In patients admitted to hospital for ACS, statins may reduce hospital mortality when treatment is initiated on the first day of hospitalization. PMID- 22295884 TI - Intramuscular drotaverine and diclofenac in acute renal colic: a comparative study of analgesic efficacy and safety. AB - OBJECTIVE: To evaluate the analgesic efficacy and safety of intramuscular drotaverine hydrochloride vs diclofenac sodium in treatment of acute renal colic. METHODS: We conducted a randomized, single-blind study comparing single intramuscular doses of drotaverine hydrochloride (80 mg) vs diclofenac sodium (75 mg) on 100 patients (50 in each arm) presenting to the emergency department (ED) with renal colic. Subjects with inadequate pain relief at 30 minutes received rescue intramuscular tramadol (100 mg). Pain intensity was recorded using a visual analog scale (VAS), which is the primary outcome measure of this study, before drug administration and 30 and 60 minutes afterwards. The drug effectiveness was defined as >=50% decrease in pain intensity 60 minutes after intramuscular administration, without exacerbation during the following 2 hours. The need for rescue medication and the presence of adverse effects were considered as secondary outcome of the study. RESULT: VAS decreased significantly (P < 0.001) with both drotaverine (52.4%) and diclofenac (49%) at 30 minutes. Reduction of VAS at 60 minutes was 61.3% with drotaverine in comparison to 60.4% with diclofenac. Forty-five patients (90%) in the drotaverine group and 44 (88%) in the diclofenac group found the therapy effective. The need for rescue medication was in five patients of the drotaverine group and six patients in the diclofenac group. There was no significant difference in safety profile in the study groups. CONCLUSION: The efficacy and safety of drotaverine as analgesic in renal colic is noninferior to diclofenac and may be used as an alternative or add on therapy to currently available options. PMID- 22295885 TI - Relational and sexual fluidity in females partnered with male-to-female transsexual persons. AB - This paper reports on a study examining sexuality in females who remain partnered with male-to-female transsexual persons. Participants' self-view and sexual fluidity following their partners' transition from man to woman is examined. Sixteen females participated in in-depth, semi-structured interviews. An inductive process of data analysis was conducted, using the constant comparative method, an iterative process by which data are compared within and across subjects. Data were collected until thematic saturation was achieved. Four themes related to sexuality emerged: (1) questioning of sexual orientation; (2) sexual orientation categorization; (3) relational fluidity without sexual relations; and (4) relational fluidity with sexual relations. Participants maintained a heterosexual identity, yet modified their self-view to include an identity that reflected their reformed relationship. The majority of the respondents reported sexual lives that were active or evolving. Others remained in relationships that no longer included sexual activity. The study findings highlight the potential fluidity within the sexual and relational lives of females, and can enhance healthcare providers' preparedness and efficacy with diverse populations. Providers are in a unique position to offer resources to patients who identify as sexually or gender-diverse, or who are in relationships with sexually or gender diverse persons. PMID- 22295886 TI - Ion binding and internal hydration in the multidrug resistance secondary active transporter NorM investigated by molecular dynamics simulations. AB - Recently, a 3.65 A resolution structure of the transporter NorM from the multidrug and toxic compound extrusion family has been determined in the outward facing conformation. This antiporter uses electrochemical gradients to drive substrate export of a large class of antibiotic and toxic compounds in exchange for small monovalent cations (H(+) and Na(+)), but the molecular details of this mechanism are still largely unknown. Here we report all-atom molecular dynamics simulations of NorM, with and without the bound Na(+) cation and at different ion concentrations. Spontaneous binding of Na(+) is observed in several independent simulations with transient ion binding to D36 being necessary to reach the final binding site for which two competitive binding modes occur. Finally, the simulations indicate that the extracellular vestibule of the transporter invariably loses its characteristic V shape indicated by the crystallographic data, and it is reduced to a narrow permeation pathway lined by polar residues that can act as a specific pore for the transport of small cations. This event, together with the available structures of evolutionarily related transporters of the major facilitator superfamily (MFS), suggests that differences in the hydrophobic content of the extracellular vestibule may be characteristic of multidrug resistance transporters in contrast to substrate-selective members of the MFS. PMID- 22295888 TI - Pediatric hepatotoxicity associated with polygermander (teucrium polium). PMID- 22295890 TI - Quercetin and catechin synergistically inhibit angiotensin II-induced redox dependent signalling pathways in vascular smooth muscle cells from hypertensive rats. AB - Dietary flavonoids, present in different amount in foods, are associated with the prevention of hypertension, but little is known about the interactions between them. The aim of this study was to explore the effect of quercetin (Q), catechin (C) and the mixture, on Angiotensin II (AngII)-induced redox-dependent signalling pathways and cell behaviour. Mesenteric smooth muscle cells (MesSMC) from spontaneously hypertensive rats (SHR) were incubated with AngII (0.1 MUmol/L) alone, or with the mixture of low concentrations of Q and C. AngII-increased ROS production was reduced by the mixture of separately ineffective low concentration of Q (15 MUmol/L) plus C (20 MUmol/L). This mixture reduced AngII-stimulated NAD(P)H oxidase activation and p47phox translocation to the cell membrane, without affecting Nox2 expression. Co-incubation of Q + C significantly inhibited AngII-induced migration and proliferation, and these effects were independent of p-ERK1/2 and related with reduced p38MAPK phosphorylation. These findings demonstrated that low concentrations of singly non-effective flavonoids when are combined exert a synergistic effect in inhibiting AngII-induced redox-sensitive signalling pathways. PMID- 22295891 TI - Fish oil supplement alters markers of inflammatory and nutritional status in colorectal cancer patients. AB - Inflammation is a common feature in cancer. The presence and magnitude of the chronic systemic inflammatory responses may produce progressive nutritional decline. This study aims at investigating whether there are changes in inflammation markers and/or in nutritional status of patients with colorectal cancer undergoing chemotherapy who were supplemented with fish oil. The clinical trial was conducted with 23 patients randomly distributed in 2 groups. The supplemented group (SG) consumed 2 g of fish oil containing 600 milligrams of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for 9 wk. Nutritional and inflammatory markers status was available, both at a baseline (M0), and after 9 wk of chemotherapy (M9) in the SG and in the nonsupplemented group (NSG). Statistical analysis was conducted with STATA 11.0 software. SG and NSG presented the same baseline characteristics (P > 0.05). Nutritional status indicators such as body mass index and body weight were modified only in the NSG when comparing baseline and M9, P = 0.03 and P = 0.01 respectively, whereas in SG these indicators did not vary. Patients supplemented with fish oil (SG) showed a clinically relevant decrease in the C-reactive protein/albumin relation (P = 0.005). Low doses of fish oil supplement can positively modulate the nutritional status and the C-reative protein/albumin ratio. PMID- 22295892 TI - Development of photostable gastro retentive formulation for nifedipine using low density polypropylene microporous particles. AB - The aim of this study was to develop photostable gastro retentive formulation for nifedipine loading into low-density polypropylene microporous particles (Accurel MP 1000(r)) by a solvent evaporation technique using the 32 factorial design. Yield, drug loading, surface topography, thermal properties, crystal characteristics, photostability and in vitro drug release were studied. Optimized microparticles formulated into a capsule were evaluated for the dissolution study and compared with marketed formulation. Higher values of T(50%), time required for 50% degradation of drug with threefold and 1.5-fold decrease in degradation rate constant (K) under UV and fluorescent lamp were observed for the microparticles, respectively, as compared to pure nifedipine indicated remarkable improved photostability. Microparticles showed good floating ability in 0.1N HCl with initial burst release (16-29%) followed by the zero-order drug release up to 8 h. The capsule formulation followed the ideal modified release pattern. PMID- 22295893 TI - Prevalence and outcome of Middle-eastern Arab and South Asian patients hospitalized with heart failure: insight from a 20-year registry in a Middle eastern country (1991-2010). AB - INTRODUCTION: The clinical characteristics and outcome of patients hospitalized with heart failure vary according to ethnicities. BACKGROUND: Limited epidemiologic data are available about the clinical characteristics and outcome of heart failure (HF) patients among non-Caucasian populations. METHODS: Between 1 January 1991 and 31 December 2010; 41 453 consecutive patients were hospitalized at Hamad General Hospital, Doha, Qatar for cardiac reasons. Patients were into two groups; hospitalized with HF (n = 7069) and hospitalized for non-HF (no-HF). Among HF patients Sub-analysis was made according to ethnicity; Middle eastern Arabs (MEA) (n = 5227) versus South Asian (SA) (n = 1289) patients. RESULTS: HF patients were older and more likely to be female when compared to non HF patients. HF patients were also more likely to have diabetes mellitus (DM), hypertension (HTN), atrial fibrillation (AF) and renal impairment when compared to non-HF patients. SA HF patients younger and less likely to have DM, HTN and AF when compared to MEA patients. Over the 20-years period there was decrease in in hospital mortality and stroke rates regardless of ethnicity (death; 8.3% to 4.8%, stroke; 0.8% to 0.1%; all P = 0.001). CONCLUSION: HF patients in the Middle East present at relatively younger age regardless of ethnicity. In-hospital mortality and stroke rates decreased significantly over the 20-years. PMID- 22295894 TI - Glomerular and tubulointerstitial miR-638, miR-198 and miR-146a expression in lupus nephritis. AB - AIM: MicroRNAs (miRNAs) play important roles in the pathogenesis of autoimmune diseases. We studied the intra-renal expression of miRNA targets that were reported to be differentially expressed in peripheral blood or urine between lupus nephritis (LN) patients and normal controls. METHODS: We quantified the expression of in glomerulus and tubulointerstitium of miR-146a, miR-155, miR-198 miR-638 and miR-663 in 42 patients with LN and 10 healthy controls. RESULTS: As compared with controls, LN patients had lower glomerular expression of miR-638 (P < 0.001) but higher tubulointerstitial expression of this target (P = 0.001). Both glomerular and tubulointerstitial expression of miR-198 were higher in LN patients than controls (P < 0.001). For miR-146a, LN patients only had higher expression in glomerulus (P = 0.005) but not in tubulointerstitium. Tubulointerstitial miR-638 expression was significantly correlated with proteinuria (r = 0.404; P = 0.022) and disease activity score (r = 0.454; P = 0.008), while glomerular miR-146a expressions were correlated with estimated GFR (r = 0.453; P = 0.028) and histological activity index (r = 0.494; P = 0.027). CONCLUSION: We found that intra-renal expression of miR-638, miR-198 and miR-146a are differentially expressed between LN patients and normal controls. Furthermore, the degree of change in glomerular miR-146a and tubulointerstitial miR-638 expression correlated with clinical disease severity. The results suggested that these miRNA targets may play a role in the pathogenesis of lupus nephritis. PMID- 22295895 TI - Simultaneous population pharmacokinetic modelling of ketamine and three major metabolites in patients with treatment-resistant bipolar depression. AB - AIM: To construct a population pharmacokinetic (popPK) model for ketamine (Ket), norketamine (norKet), dehydronorketamine (DHNK), hydroxynorketamine (2S,6S;2R,6R) HNK) and hydroxyketamine (HK) in patients with treatment-resistant bipolar depression. METHOD: Plasma samples were collected at 40, 80, 110, 230 min on day 1, 2 and 3 in nine patients following a 40 min infusion of (R,S)-Ket (0.5 mg kg 1) and analyzed for Ket, norKet and DHNK enantiomers and (2S,6S;2R,6R)-HNK, (2S,6S;2R,6R)-HK and (2S,6R;2R,6S)-HK. A compartmental popPK model was constructed that included all quantified analytes, and unknown parameters were estimated with an iterative two-stage algorithm in ADAPT5. RESULTS: Ket, norKet, DHNK and (2S,6S;2R,6R)-HNK were present during the first 230 min post infusion and significant concentrations (>5 ng ml-1) were observed on day 1. Plasma concentrations of (2S,6S;2R,6R)-HK and (2S,6R;2R,6S)-HK were below the limit of quantification. The average (S) : (R) plasma concentrations for Ket and DHNK were <1.0 while no significant enantioselectivity was observed for norKet. There were large inter-patient variations in terminal half-lives and relative metabolite concentrations; at 230 min (R,S)-DHNK was the major metabolite in four out of nine patients, (R,S)-norKet in three out of nine patients and (2S,6S;2R,6R)-HNK in two out of nine patients. The final PK model included three compartments for (R,S)-Ket, two compartments for (R,S)-norKet and single compartments for DHNK and HNK. All PK profiles were well described, and parameters for (R,S)-Ket and (R,S) norKet were in agreement with prior estimates. CONCLUSION: This represents the first PK analysis of (2S,6S;2R,6R)-HNK and (R,S)-DHNK. The results demonstrate that while norKet is the initial metabolite, it is not the main metabolite suggesting that future Ket studies should include the analysis of the major metabolites. PMID- 22295896 TI - Into and out of Africa--taking over from Denis Burkitt. AB - Denis Burkitt's description of the eponymous lymphoma in 1958 in Uganda, opened up a vast and important field of enquiry in haematology and oncology. His pioneering experiments with chemotherapy demonstrated the possibility of cure, often with a single dose. His geographical explorations showed the tumour to be delimited by climate, suggesting an infectious cause vectored by mosquitoes. His clinical observations furthered the field of cancer immunotherapy. And his collegial, inquisitive nature facilitated the development of an enduring cancer research centre in Kampala. Burkitt's legacy in Uganda has wide-reaching effects that endure not only in Uganda but also throughout the haematology-oncology community to this day. PMID- 22295897 TI - Raising children in America: Korean parents' experiences. AB - This qualitative description study was designed to describe Korean American parents' perceptions of challenges and difficulties they encounter while raising their children in the USA. A convenience sampling of 21 parents of adolescents aged 11-14 years recruited from the Midwest Korean American community participated in the study. Data were collected using in-depth, face-to-face interviews, which took place in agreed-upon, convenient locations. All interviews were audiotaped and transcribed in Korean and the transcripts were translated into English. Qualitative content analysis revealed that the main stresses that parents encountered while raising their children in the USA were inability to advocate for children, feeling uneasy and insecure about incompatible American culture, ambivalence towards children's ethnic identities, and feeling alienated. In relation to these stresses, parents often felt inadequate, ashamed, guilty, regretful and powerless. The findings demonstrated the importance of understanding parents' feelings that are deeply embedded in the conflicted parent child relationships and their perceptions of being parents in the USA. The present study highlights the need for and importance of providing intervention programmes for parents, particularly programmes that would empower parents, strengthen parent-child relationships and address ways to integrate two very different cultures while upholding ethnic identity and pride. PMID- 22295898 TI - Double-masked, placebo-controlled study of intravenous levetiracetam for the treatment of status epilepticus and acute repetitive seizures in dogs. AB - BACKGROUND: Status epilepticus (SE) and acute repetitive seizures (ARS) are common canine neurologic emergencies. No evidence-based studies are available to guide treatment in veterinary patients. Parenteral levetiracetam (LEV) has many favorable properties for the emergency treatment of seizures, but its safety and efficacy in dogs for SE and ARS are unknown. HYPOTHESIS: Intravenous LEV is superior to placebo in controlling seizures in dogs with SE or ARS after treatment with IV diazepam. ANIMALS: Nineteen client-owned dogs admitted for SE or ARS. METHODS: Randomized, placebo-controlled, double-masked study. Dogs with SE or ARS were randomized to receive IV LEV (30 or 60 mg/kg using an adaptive dose-escalation approach) or placebo, in addition to standard of care treatment. They were monitored for at least 24 hours after admission for additional seizures. RESULTS: The responder rate (defined as dogs with no additional seizures after administration of the study medication) after LEV was 56% compared with 10% for placebo (P = .06). Dogs in the placebo group required significantly more boluses of diazepam compared with the LEV group (P < .03). Seizure etiologies identified were idiopathic epilepsy (n = 10), inflammatory central nervous system disease (n = 4), intracranial neoplasia (n = 2), hepatic encephalopathy (n = 1), and 2 dogs had no cause determined. No serious adverse effects were attributable to LEV administration. CONCLUSIONS AND CLINICAL IMPORTANCE: LEV was safe and potentially effective for the treatment of SE and ARS in these client-owned dogs. Larger, controlled clinical trials are needed to confirm this preliminary observation. PMID- 22295899 TI - Polybrominated diphenyl ethers in U.S. sewage sludges and biosolids: temporal and geographical trends and uptake by corn following land application. AB - Polybrominated diphenyl ethers (PBDEs) have been used extensively to flame-retard polymers and textiles. These persistent chemicals enter wastewater streams following manufacture, use, and disposal, concentrating in the settled solids during treatment. Land application of stabilized sewage sludge (known as biosolids) can contribute PBDEs to terrestrial systems. Monitoring sludge/biosolids contaminant burdens may be valuable in revealing trends in societal chemical usage and environmental release. In archived Chicago area sludges/biosolids from 1975 to 2008, penta-BDE concentrations increased and then plateaued after about 2000. Penta-BDE manufacture in the United States ended in December 2004. Deca-BDE concentrations in biosolids rose from 1995 to 2008, doubling on a 5-year interval. Evaluation of U.S. Environmental Protection Agency Targeted National Sewage Sludge Survey data from 2006 to 2007 revealed highest penta-BDE biosolids levels from western and lowest from northeastern wastewater treatment plants (2120 and 1530 MUg/kg, respectively), consistent with patterns reported in some recent indoor dust and human blood studies. No significant regional trends were observed for deca-BDE concentrations. Congener patterns in contemporary Chicago biosolids support the contention that BDE-209 can be dehalogenated to less brominated congeners. Biosolids application on agricultural fields increased PBDE soil concentrations. However, corn grown thereon did not exhibit measurable PBDE uptake; perhaps due to low bioavailability of the biosolids-associated flame retardants. PMID- 22295900 TI - Morphine and memantine treatment of long-standing complex regional pain syndrome. PMID- 22295901 TI - Oxygen adsorption on beta-quartz model surfaces: some insights from density functional theory calculations and semiclassical time-dependent dynamics. AB - The O/beta-quartz interaction is described by combining our time-dependent semiclassical approach to atom-molecule/surface scattering with first-principles electronic structure calculations at the DFT (PBE0) level of accuracy. In particular, the O, O(2) interaction potentials with an on-top Si atom and its nearest O atom both localized over three different silica clusters have been calculated as a function of the oxygen-silica approaching distance. The calculated DFT potential energy surface has been used in semiclassical trajectory calculations to investigate the sticking and inelastic reflection of oxygen atoms from a model beta-quartz surface. The collisional mechanism, including the role played by the phonon dynamics, is brought to light and accurate sticking probabilities are calculated at five impact energies in the range [0.05-0.8] eV and T(S) = 1000 K. The different catalytic response of beta-quartz and beta cristobobalite to the atomic oxygen flux is also discussed and highlighted. PMID- 22295902 TI - Reorientation of cellulose nanowhiskers in agarose hydrogels under tensile loading. AB - Agarose hydrogels filled with cellulose nanowhiskers were strained in uniaxial stretching under different humidity conditions. The orientation of the cellulose whiskers was examined before and after testing with an X-ray laboratory source and monitored in situ during loading by synchrotron X-ray diffraction. The aim of this approach was to determine the process parameters for reorienting the cellulose nanowhiskers toward a preferential direction. Results show that a controlled drying of the hydrogel is essential to establish interactions between the matrix and the cellulose nanowhiskers which allow for a stress transfer during stretching and thereby promote their alignment. Rewetting of the sample after reorientation of the cellulose nanowhiskers circumvents a critical increase of stress. This improves the extensibility of the hydrogel and is accompanied by a further moderate alignment of the cellulose nanowhiskers. Following this protocol, cellulose nanowhiskers with an initial random distribution can be reoriented toward a preferential direction, creating anisotropic nanocomposites. PMID- 22295903 TI - Aflaquinolones A-G: secondary metabolites from marine and fungicolous isolates of Aspergillus spp. AB - Seven new compounds (aflaquinolones A-G; 1-7) containing dihydroquinolin-2-one and terpenoid units have been isolated from two different fungal sources. Two of these metabolites (1 and 2) were obtained from a Hawaiian fungicolous isolate of Aspergillus sp. (section Flavipedes; MYC-2048 = NRRL 58570), while the others were obtained from a marine Aspergillus isolate (SF-5044) collected in Korea. The structures of these compounds were determined mainly by analysis of NMR and MS data. Relative and absolute configurations were assigned on the basis of NOESY data and (1)H NMR J-values, comparison of calculated and experimental ECD spectra, and analysis of a Mosher's ester derivative of 2. Several known compounds, including alantrypinone, aspochalasins I and J, methyl 3,4,5 trimethoxy-2((2-((3-pyridinylcarbonyl)amino)benzoyl)amino)benzoate, and trans dehydrocurvularin were also encountered in the extract of the Hawaiian isolate. PMID- 22295904 TI - Hydrophobic core flexibility modulates enzyme activity in HIV-1 protease. AB - Human immunodeficiency virus Type-1 (HIV-1) protease is crucial for viral maturation and infectivity. Studies of protease dynamics suggest that the rearrangement of the hydrophobic core is essential for enzyme activity. Many mutations in the hydrophobic core are also associated with drug resistance and may modulate the core flexibility. To test the role of flexibility in protease activity, pairs of cysteines were introduced at the interfaces of flexible regions remote from the active site. Disulfide bond formation was confirmed by crystal structures and by alkylation of free cysteines and mass spectrometry. Oxidized and reduced crystal structures of these variants show the overall structure of the protease is retained. However, cross-linking the cysteines led to drastic loss in enzyme activity, which was regained upon reducing the disulfide cross-links. Molecular dynamics simulations showed that altered dynamics propagated throughout the enzyme from the engineered disulfide. Thus, altered flexibility within the hydrophobic core can modulate HIV-1 protease activity, supporting the hypothesis that drug resistant mutations distal from the active site can alter the balance between substrate turnover and inhibitor binding by modulating enzyme activity. PMID- 22295905 TI - Dextran and protamine-based solid lipid nanoparticles as potential vectors for the treatment of X-linked juvenile retinoschisis. AB - The goal of the present study was to analyze the potential application of nonviral vectors based on solid lipid nanoparticles (SLN) for the treatment of ocular diseases by gene therapy, specifically X-linked juvenile retinoschisis (XLRS). Vectors were prepared with SLN, dextran, protamine, and a plasmid (pCMS EGFP or pCEP4-RS1). Formulations were characterized and the in vitro transfection capacity as well as the cellular uptake and the intracellular trafficking were studied in ARPE-19 cells. Formulations were also tested in vivo in Wistar rat eyes, and the efficacy was studied by monitoring the expression of enhanced green fluorescent protein (EGFP) after intravitreal, subretinal, and topical administration. The presence of dextran and protamine in the SLN improved greatly the expression of retinoschisin and EGFP in ARPE-19 cells. The nuclear localization signals of protamine, its ability to protect the DNA, and a shift in the entry mechanism from caveola-mediated to clathrin-mediated endocytosis promoted by the dextran, justify the increase in transfection. After ocular administration of the dextran-protamine-DNA-SLN complex to rat eyes, we detected the expression of EGFP in various types of cells depending on the administration route. Our vectors were also able to transfect corneal cells after topical application. We have demonstrated the potential usefulness of our nonviral vectors loaded with XLRS1 plasmid and provided evidence for their potential application for the management or treatment of degenerative retinal disorders as well as ocular surface diseases. PMID- 22295907 TI - RcsB-BglJ activates the Escherichia coli leuO gene, encoding an H-NS antagonist and pleiotropic regulator of virulence determinants. AB - The LysR-type transcription factor LeuO is involved in regulation of pathogenicity determinants and stress responses in Enterobacteriaceae, and acts as antagonist of the global repressor H-NS. Expression of the leuO gene is repressed by H-NS, and it is upregulated in stationary phase and under amino acid starvation conditions. Here, we show that the heterodimer of the FixJ/NarL-type transcription regulators RcsB and BglJ strongly activates expression of leuO and that RcsB-BglJ regulates additional loci. Activation of leuO by RcsB-BglJ is independent of the Rcs phosphorelay system. RcsB-BglJ binds to the leuO promoter region and activates one of two leuO promoters mapped in vivo. Moreover, LeuO antagonizes activation of leuO by RcsB-BglJ and acts as negative autoregulator in vivo and in vitro. Further, the H-NS paralogue StpA causes repression of leuO in addition to H-NS. Together, our data suggest a complex arrangement of regulatory elements and they indicate a feedback control mechanism of leuO expression. PMID- 22295908 TI - Identification and characterization of ANAC042, a transcription factor family gene involved in the regulation of camalexin biosynthesis in Arabidopsis. AB - Camalexin is the major phytoalexin in Arabidopsis. An almost complete set of camalexin biosynthetic enzymes have been elucidated but only limited information is available regarding molecular mechanisms regulating camalexin biosynthesis. Here, we demonstrate that ANAC042, a member of the NAM, ATAF1/2, and CUC2 (NAC) transcription factor family genes, is involved in camalexin biosynthesis induction. T-DNA insertion mutants of ANAC042 failed to accumulate camalexin at the levels achieved in the wild type, and were highly susceptible to Alternaria brassicicola infection. The camalexin biosynthetic genes CYP71A12, CYP71A13, and CYP71B15/PAD3 were not fully induced in the mutants, indicating that the camalexin defects were at least partly a result of reduced expression levels of these P450 genes. beta-Glucuronidase (GUS)-reporter assays demonstrated tissue specific induction of ANAC042 in response to differential pathogen infections. Bacterial flagellin (Flg22) induced ANAC042 expression in the root-elongation zone, the camalexin biosynthetic site, and the induction was abolished in the presence of either a general kinase inhibitor (K252a), a Ca(2+)-chelator (BAPTA), or methyl jasmonate. The GUS-reporter assay revealed repression of the Flg22 dependent ANAC042 expression in the ethylene-insensitive ein2-1 background but not in sid2-2 plants defective for salicylic acid biosynthesis. We discuss ANAC042 as a key transcription factor involved in previously unknown regulatory mechanisms to induce phytoalexin biosynthesis in Arabidopsis. PMID- 22295909 TI - Solid-state selective (13)C excitation and spin diffusion NMR to resolve spatial dimensions in plant cell walls. AB - The average spatial dimensions between major biopolymers within the plant cell wall can be resolved using a solid-state NMR technique referred to as a (13)C cross-polarization (CP) SELDOM (selectively by destruction of magnetization) with a mixing time delay for spin diffusion. Selective excitation of specific aromatic lignin carbons indicates that lignin is in close proximity to hemicellulose followed by amorphous and finally crystalline cellulose. (13)C spin diffusion time constants (T(SD)) were extracted using a two-site spin diffusion theory developed for (13)C nuclei under magic angle spinning (MAS) conditions. These time constants were then used to calculate an average lower-limit spin diffusion length between chemical groups within the plant cell wall. The results on untreated (13)C enriched corn stover stem reveal that the lignin carbons are, on average, located at distances ~0.7-2.0 nm from the carbons in hemicellulose and cellulose, whereas the pretreated material had larger separations. PMID- 22295910 TI - Postmortem findings in a patient with cerebral amyloid angiopathy actively treated with corticosteroid. AB - We examined histopathological changes in cerebrovascular amyloid deposition in a patient with cerebral amyloid angiopathy receiving corticosteroid therapy. A 69 year-old female developed subacute onset cognitive decline, and magnetic resonance image (MRI) showed subarachnoid hemorrhage with leptomeningeal enhancement. She entered in an apathetic state due to communicating hydrocephalus and a ventricle-peritoneal (V-P) shunt operation was performed. Brain biopsy disclosed multiple cortical microhemorrhages and severe Congophilic angiopathy with positive Abeta-immunoreactivity in most vessels. Inflammatory mononuclear cells surrounded a few severe amyloid-laden leptomeningeal vessels. She received high-dose corticosteroid, which was slowly tapered. She gradually recovered but finally died 1.5 years later with no recurrence of CAA-related hemorrhages. Postmortem examination of the brain showed multiple old microhemorrhages in the cortex and extensive degeneration of cerebral white matter. The cortical and leptomeningeal vascular walls showed a few Congophilic amyloid deposits, but small deposits with Abeta-immunoreactivity were frequently seen. There was no infiltration of inflammatory cells in either leptomeninges or vascular walls. Electron microscopy revealed sparse aggregation of amyloid fibrils in significant numbers of vascular walls. Biochemical analysis disclosed that Abeta1-40 immunoreactive amyloid protein fractions obtained from the patient's leptomeninges were very small in amount. Comparing the previous biopsy findings with those at autopsy, the total disappearance of the inflammatory cell infiltration and diminishing of the cerebrovascular amyloid deposits were noted. PMID- 22295911 TI - Cytosolic Ca2+ regulates the energization of isolated brain mitochondria by formation of pyruvate through the malate-aspartate shuttle. AB - The glutamate-dependent respiration of isolated BM (brain mitochondria) is regulated by Ca2+(cyt) (cytosolic Ca2+) (S0.5=225+/-22 nM) through its effects on aralar. We now also demonstrate that the alpha-glycerophosphate-dependent respiration is controlled by Ca2+(cyt) (S0.5=60+/-10 nM). At higher Ca2+(cyt) (>600 nM), BM accumulate Ca2+ which enhances the rate of intramitochondrial dehydrogenases. The Ca2+-induced increments of state 3 respiration decrease with substrate in the order glutamate>alpha-oxoglutarate>isocitrate>alpha glycerophosphate>pyruvate. Whereas the oxidation of pyruvate is only slightly influenced by Ca2+(cyt), we show that the formation of pyruvate is tightly controlled by Ca2+(cyt). Through its common substrate couple NADH/NAD+, the formation of pyruvate by LDH (lactate dehydrogenase) is linked to the MAS (malate aspartate shuttle) with aralar as a central component. A rise in Ca2+(cyt) in a reconstituted system consisting of BM, cytosolic enzymes of MAS and LDH causes an up to 5-fold enhancement of OXPHOS (oxidative phosphorylation) rates that is due to an increased substrate supply, acting in a manner similar to a 'gas pedal'. In contrast, Ca2+(mit) (intramitochondrial Ca2+) regulates the oxidation rates of substrates which are present within the mitochondrial matrix. We postulate that Ca2+(cyt) is a key factor in adjusting the mitochondrial energization to the requirements of intact neurons. PMID- 22295912 TI - Resolution of syndromic craniosynostosis-associated Chiari malformation Type I without suboccipital decompression after posterior cranial vault release. AB - Chiari malformation Type I (CM-I) is associated with syndromic and nonsyndromic craniosynostosis in pediatric patients, and the surgical management of CM-I in such cases is controversial. Previous guidelines have recommended simultaneous cranial vault expansion and suboccipital decompression. However, spontaneous resolution of CM-I has been observed, and the combined procedure carries additional surgical risks. The authors report the case of a 6-month-old boy with Crouzon syndrome, CM-I, and a cervical syrinx who underwent posterior cranial vault release without suboccipital decompression. Imaging at the 3-month follow up visit demonstrated complete resolution of the CM-I, improvement in CSF flow, and reduction in the size of the syrinx. This case suggests that up-front suboccipital decompression may not be necessary in patients with craniosynostosis and CM-I. A strategy of initial cranial vault release, followed by watchful waiting and radiographic surveillance, is proposed. PMID- 22295913 TI - Development of secondary unilateral coronal suture synostosis with a sagittal suture synostosis in a nonsyndromic patient. AB - Multiple-suture synostosis is typically associated with syndromic craniosynostosis but has been occasionally reported in large series of nonsyndromic children. The diagnosis of multiple fused sutures usually occurs at the same time, but rarely has the chronological development of a secondary suture synostosis been noted. The development of secondary bicoronal suture synostosis requiring surgical intervention has only been reported, to date, after surgical intervention and is hypothesized to arise from a disruption of inhibitory factors from the dura. The disinhibition of these factors permits the sutures to then fuse at an early stage. The authors report on a patient who developed secondary unilateral coronal synostosis after the diagnosis of an isolated sagittal synostosis. The secondary synostosis was identified at the time of the initial surgical intervention and ultimately required a second procedure of a frontoorbital advancement. The clinical appearance of this phenomenon may be subtle, and surgeons should monitor for the presence of secondary synostosis during surgery as it may require intervention. Failure to identify the secondary synostosis may necessitate another surgery or result in a poor cosmetic outcome. The authors recommend close clinical follow-up for the short term in patients with isolated sagittal synostosis. PMID- 22295914 TI - Application of neuromuscular blockade and intraoperative 3D imaging in the reduction of basilar invagination. AB - OBJECT: The treatment of basilar invagination in the pediatric age group is dependent on the possibility of preoperative reduction. Reducible lesions obviate a ventral decompression and require a dorsal-only approach for stabilization with or without a suboccipital decompression. METHODS: The authors describe a technique of intraoperative reduction of basilar invagination with the use of general anesthesia and neuromuscular blockade in the presence of crown halo traction. Using the O-arm device, a 3D CT scan is generated in the sagittal plane to demonstrate the reduction intraoperatively. This technique was successful in 6 pediatric patients with basilar invagination. RESULTS: The average age of the patients was 10.8 years, and they were followed for a mean period of 8.5 months. The patients had mild basilar invagination or partial reduction in extension on preoperative MR imaging. Intraoperative reduction was demonstrated in all patients by using the reported technique with intraoperative CT. All patients underwent occipitocervical fusion, and all but one underwent a suboccipital decompression. There were no complications related to the operation, and all but one reported improvement of symptoms on the last postoperative visit. CONCLUSIONS: Intraoperative reduction performed using neuromuscular blockade and intraoperative traction is an effective method for further reduction of basilar invagination in the pediatric age group. This is the first reported application of intraoperative CT imaging performed using the O-arm device in craniocervical surgery in which successful reduction is demonstrated in detail. PMID- 22295915 TI - Comparison of outcomes following decompressive craniectomy in children with accidental and nonaccidental blunt cranial trauma. AB - OBJECT: The goal of this study was to compare clinical outcomes following decompressive craniectomy performed for intracranial hypertension in children with nonaccidental, blunt cranial trauma with outcomes of decompressive craniectomy in children injured by other mechanisms. METHODS: All children in a prospectively acquired database of trauma admissions who underwent decompressive craniectomy over a 9-year span, beginning January 1, 2000, are the basis for this study. Clinical records and neuroimaging studies were systematically reviewed. RESULTS: Thirty-seven children met the inclusion criteria. Nonaccidental head trauma was the most common mechanism of injury (38%). The mortality rate in patients with abusive brain injury (35.7%) was significantly higher (p < 0.05) than in patients with other causes of traumatic brain injury (4.3%). Children with inflicted head injuries had a 12-fold increase in the odds of death and 3 fold increase in the odds of a poor outcome (King's Outcome Scale for Closed Head Injury score of 1, 2, or 3). CONCLUSIONS: Children with nonaccidental blunt cranial trauma have significantly higher mortality following decompressive craniectomy than do children with other mechanisms of injury. This understanding can be interpreted to mean either that the threshold for decompression should be lower in children with nonaccidental closed head injury or that decompression is unlikely to alter the path to a fatal outcome. If decompressive craniectomy is to be effective in reducing mortality in the setting of nonaccidental blunt cranial trauma, it should be done quite early. PMID- 22295916 TI - Performance analysis of winter activity protection headgear for young children. AB - OBJECT: The purpose of this study was to evaluate how currently used helmets would perform for winter play activities, such as tobogganing. In Canada and northern parts of the US, the advent of winter is followed by an increase in visits to hospital emergency departments by young children presenting with head injuries resulting from winter activities. Sliding, skating, skiing, and snowboarding all involve risks of head injury from situations such as falling on ice or sliding into stationary objects. This study compared the protective characteristics of helmets used by young children (< 7 years of age) participating in winter recreational activities. METHODS: Ice hockey, alpine ski, and bicycling helmets were impacted at 2.0, 4.0, 6.0, and 8.0 m/second at the front and side impact location by using a monorail drop rig. RESULTS: The results for the front impact showed that the ice hockey helmet protected the child significantly better at 2 and 4 m/second when considering both linear and angular peak acceleration. The bicycle helmet performed significantly better than the other 2 helmets at 8 m/second for the front location and only angularly for the side impacts. CONCLUSIONS: Depending on the impact velocity of the hazard, the type of helmet significantly affected the risk of brain injury. PMID- 22295917 TI - Posterior fossa epidural hematomas in children: clinical experience with 40 cases. AB - OBJECT: Traumatic posterior fossa epidural hematoma (PFEDH) is rare, but among children it may have a slightly higher incidence. With the widespread use of CT scanning, the diagnosis of PFEDH can be established more accurately, leading to an increased incidence of the lesion and possibly to a better patient prognosis. This study presents 40 pediatric cases with PFEDH. METHODS: The authors assessed the type of trauma, clinical findings on admission, Glasgow Coma Scale scores, CT findings (thickness of the hematoma, bone fracture, compression of the fourth ventricle, and ventricle enlargement), type of treatment, clinical course, and prognosis. Early postoperative CT scans (within the first 6 hours) were obtained and reviewed in all surgical cases. RESULTS: Twenty-nine patients underwent surgery and 11 patients received conservative therapy and close follow-up. All patients fared well, and there was no surgical mortality or morbidity. CONCLUSIONS: Based on the data in this large series, the authors conclude that PFEDH in children can be treated in experienced centers with excellent outcome, and there is no need to avoid surgery when it is indicated. PMID- 22295918 TI - Rotatory subluxation: experience from the Hospital for Sick Children. AB - OBJECT: Diagnosis and management of atlantoaxial rotatory subluxation (AARS) is challenging because of its variability in clinical presentation. Although several treatment modalities have been employed, there remains no consensus on the most appropriate therapy. The authors explore this issue in their 9-year series on AARS. METHODS: Records of patients diagnosed radiologically and clinically with AARS between May 2001 and March 2010 were retrospectively reviewed. Of 40 patients identified, 24 were male and were on average 8.5 years of age (range 15 months-16 years). Causes of AARS included trauma, congenital abnormalities, juvenile rheumatoid arthritis, infection, postsurgical event, and cryptogenic disease. Four patients had dual etiologies. Symptom duration varied: 29 patients had symptoms for less than 4 weeks, 5 patients had symptoms between 1 and 3 months, and 6 patients had symptoms for 3 months or more. RESULTS: Treatment with a cervical collar was sufficient in 21 patients. In 1 patient collar management failed and halter traction was used to reduce the subluxation. Seven patients underwent initial halter traction, but in 4 the subluxation progressed and the patients required halo traction. A halo vest was placed in 2 patients on presentation because the rotatory subluxation was severe; both patients required subsequent operative fusion. One patient required decompression and fusion due to severe canal compromise and myelopathy. All patients requiring fusion presented with subacute symptoms. CONCLUSIONS: Management of AARS varies due to the spectrum of clinical presentations. Patients presenting acutely without neurological deficits can likely undergo collar therapy; those in whom the subluxation cannot be reduced or who present with a neurological deficit may require traction and/or surgical fixation. Patients presenting subacutely may be more prone to requiring operative intervention. PMID- 22295919 TI - Risk factors of sudden death in young adult patients with myelomeningocele. AB - OBJECT: Although survival for patients with myelomeningocele has dramatically improved in recent decades, the occasional occurrence of sudden, unexplained death in young adult patients with myelomeningocele has been noted by the authors. This study was undertaken to determine risk factors for sudden death in this population. METHODS: The authors performed a retrospective chart review of patients born between 1978 and 1990 who received care at Children's Hospital Boston. The relationship between sudden death and patient demographics, presence of CSF shunt and history of shunt revisions, midbrain length as a marker for severity of hindbrain malformation, seizures, pulmonary and ventilatory dysfunction, body mass index, scoliosis, renal dysfunction, and cardiac disease was evaluated using the t-test, Fisher exact test, and logistic regression analysis. RESULTS: The age range for 106 patients in the study cohort was 19-30 years, with 58 (54.7%) women and 48 (45.3%) men. Six patients, all of whom were young women, experienced sudden death. In multivariate analysis, female sex, sleep apnea, and midbrain elongation >= 15 mm on MR imaging remained significantly associated with a higher risk of sudden death. These risk factors were cumulative, and female patients with sleep apnea and midbrain length >= 15 mm had the greatest risk (adjusted risk ratio 24.0, 95% CI 7.3-79.0; p < 0.05). No other comorbidities were found to significantly increase the risk of sudden death. CONCLUSIONS: Young adult women with myelomeningocele are at significantly increased risk of sudden death in the setting of midbrain elongation and sleep apnea. Further investigation is needed to determine the benefit of routine screening to identify at-risk patients for closer cardiopulmonary monitoring and treatment. PMID- 22295920 TI - Closure of meningomyelocele defects using acellular dermal matrix. AB - Spina bifida is the most common birth defect of the CNS, with meningomyelocele observed in 1 in 800 to 1000 infants. A single reliable method of providing adequate soft-tissue coverage (skin, but also including subcutaneous fat, fascia, and muscle) of the meningomyelocele defect while preventing dehiscence and infection has yet to be defined. This study reviews a case series of 3 patients with large meningomyeloceles treated by a single neurosurgeon /plastic surgeon team at a single institution. Following repair of the neural elements (both dura and neural placode), soft-tissue coverage (skin, but also subcutaneous tissue and fascia) was achieved using acellular dermal matrix over the neural elements, repaired with sutures, and covered with skin flaps. In this series of 3 patients, stable coverage was achieved in all patients. One patient experienced minor wound dehiscence treated with debridement and primary closure with simple relaxing incisions. This series demonstrates that the usage of acellular dermal matrix provides a stable soft-tissue coverage for large meningomyelocele defects in an easily reproducible operation preserving local soft tissue (muscle, fascia) for potential salvage operations or revisions (such as for scoliosis) as well as providing a less demanding operation on the fragile physiology of the neonate. PMID- 22295921 TI - Metastasis of soft-tissue myoepithelial carcinoma to clivus. AB - The differential diagnosis for masses involving the clivus is broad. The authors present a case of myoepithelial carcinoma metastatic to the clivus, a lesion that has not been reported to their knowledge. This 14-year-old girl with a history of myoepithelial carcinoma originating in the soft tissues of the left hip and metastatic to the lung presented with left lateral gaze palsy. Imaging demonstrated a 3 * 3-cm osteolytic mass in the clivus. Microscopic transsphenoidal resection with endoscopic assistance was performed. Pathological findings were consistent with the previously diagnosed myoepithelial carcinoma. Within 4 weeks postoperatively and 2 weeks into a chemotherapeutic regimen, the tumor exhibited progression. Radiation therapy was started and growth of the tumor was halted. Myoepithelial carcinoma should be included in the differential diagnosis for clival masses, especially in patients with previously diagnosed myoepithelial carcinoma. The primary management of this tumor should be with chemotherapy and radiation, with surgery serving only for decompression. PMID- 22295922 TI - Pediatric orbital schwannoma originating from the oculomotor nerve. AB - Intraorbital schwannoma is a rare tumor that constitutes approximately 1%-8% of all orbital tumors. The authors report a case of orbital schwannoma in a 5-year old boy who was admitted to their institute with exophthalmos and ptosis of the right eye. Computed tomography scanning and MR imaging revealed a retroocular mass in the right orbit. The tumor was successfully removed via a transcranial approach. The pathological diagnosis was schwannoma that appeared to originate from the superior branch of the oculomotor nerve. Despite the rarity of these intraorbital extraocular tumors in children, schwannomas should be differentiated from other intraorbital tumors. PMID- 22295923 TI - Endoscopic coagulation of choroid plexus hyperplasia. AB - Hydrocephalus is a clinical disorder resulting from an imbalance between the production of CSF and its resorption, of which the latter is mostly a disadvantage. In rare cases of choroid plexus papilloma or carcinoma, hydrocephalus is due to an overproduction of CSF. Choroid plexus hyperplasia (CPH) is a distinct clinicopathological entity in which the enlarged choroid plexus produces large amounts of CSF. Historically, patients with CPH were treated by shunt procedures or by microsurgical removal of the choroid plexus, which is associated with a high complication rate. In this paper the authors show that endoscopic plexus coagulation can result in restoring the equilibrium of the intracranial fluid volumes, resulting in shunt independency. In this way, both the shunt-related complications and the bleeding risks of microsurgical plexectomy are avoided. In instances of hydrocephalus, thorough efforts should be made to demonstrate the underlying pathophysiology to choose the optimal treatment, of which shunt procedures should receive the least priority. PMID- 22295924 TI - Histological analysis of the third ventricle floor in hydrocephalic and nonhydrocephalic brains: application to neuroendocrine complications following third ventriculostomy procedures. AB - OBJECT: Endocrine dysfunction following endoscopic third ventriculostomy (ETV) is rare, but it has been reported. In the present study the authors sought to determine the histological nature of the floor of the third ventricle in hydrocephalic brains to better elucidate this potential association. METHODS: Five adult cadaveric brains with hydrocephalus were examined. Specifically, the floors of the third ventricle of these specimens were studied histologically. Age matched controls without hydrocephalus were used for comparison. RESULTS: Although it was thinned in the hydrocephalic brains, the floor of the third ventricle had no significant difference between the numbers of neuronal cell bodies versus nonhydrocephalic brains. CONCLUSIONS: Although uncommon following ETV, endocrine dysfunction has been reported. Based on the present study, this is most likely to be due to the injury of normal neuronal cell bodies found in this location, even in very thinned-out tissue. PMID- 22295925 TI - Preoperative third ventricular bowing as a predictor of endoscopic third ventriculostomy success. AB - OBJECT: Patients with hydrocephalus often present with both intraventricular obstructive and communicating components, and determination of the predominant component is difficult. Other investigators have observed that third ventricular floor deformation, or "bowing" of the third ventricular floor, is a good indicator of intraventricular obstructive hydrocephalus, resulting in higher success rates with endoscopic third ventriculostomy (ETV). However, additional third ventricular bowing assessment and statistical evidence demonstrating a difference in ETV outcome with third ventricular bowing is needed. The authors hypothesized that patients with preoperative bowing of the third ventricle would exhibit greater long-term success rates after ETV and that lack of bowing would result in increased failure rates after ETV. METHODS: The authors determined success and failure for 59 ETVs performed in 56 patients, and recorded patient age, time to failure, and preoperative third ventricular anatomy, as well as history of infection, intraventricular hemorrhage, and previous shunt. Third ventricular anatomy was assessed on MR imaging for bowing, which was classified as any of the following: depression of the third ventricular floor, enlargement of the supraoptic recess, anterior curvature of the lamina terminalis, dilation of the proximal aqueduct to a greater extent than the distal aqueduct, and blunting or posterior bowing of the suprapineal recess. Univariate and multivariate analyses of ETV failure and the time to failure were performed using logistic regression and the Cox proportional hazards model, respectively. RESULTS: After adjusting for patient age and history of infection, there was a significant association between lack of anterior third ventricular preoperative bowing (either lamina terminalis, supraoptic recess, or third ventricular floor) and ETV failure (adjusted HR 2.79, 95% CI 1.08-7.20). Of the patients with bowing, 70.5% experienced success with ETV, as did 33.3% of the patients without bowing. Among the individual structures, absence of bowing in the anterior aspect of the third ventricular floor was significantly associated with censored time to ETV failure (multivariate HR 2.59, 95% CI 1.01-6.66; final model including age and history of infection). CONCLUSIONS: The presence of preoperative third ventricular bowing is predictive of ETV success, with nearly a 3-fold likelihood of success compared with patients treated with ETV in the absence of such bowing. Although bowing is predictive, 33% of patients without bowing were also treated successfully with ETV. PMID- 22295926 TI - Flow characteristics of cerebrospinal fluid shunt tubing. AB - OBJECT: Cerebrospinal fluid shunt systems malfunction for a multitude of reasons, including malpostitioning, obstruction of the ventricular or distal catheter, obstruction of the shunt valve, and catheter disruptions or disconnections. The goal of this study was to examine the hydrodynamic resistance and flow in new and explanted catheters and also in catheters with 1 or 2 straight connectors. METHODS: Explanted catheters of multiple lengths, 2-piece catheters, 3-piece catheters, and new catheters were attached to a proximal and distal manometer. A flask with artificial CSF attached to the proximal end provided flow. The flow was allowed to stabilize over 1 hour; then the change in pressure between the proximal and distal end of the catheter was measured. RESULTS: The resistance to flow was calculated for new, never-implanted catheters and compared with the resistance of explanted distal shunt catheters. The resistance of the new catheters was examined after the addition of 1 and 2 straight connectors. Explanted catheters exhibited a slight increase in the resistance to flow of artificial CSF compared with new catheters. Two-piece and 3-piece catheters had a significant increase in resistance to flow compared with new catheters. For all catheters, resistance to flow increased as length increased (new, p = 0.01; explanted, p = 0.009; 1 connector, p = 0.01; 2 connectors, p = 0.03). In this paper, effective diameter is defined as the available cross-sectional area of catheter contacted by the artificial CSF. For new and explanted catheters, a decrease in the effective diameter of the catheter was associated with an increase in the resistance to flow of artificial CSF (new, p = 0.1083; explanted, p = 0.0091). However, after the addition of 1 or 2 connectors, an inverse trend was observed: resistance to flow increased with effective diameter. CONCLUSIONS: There appears to be some increase in resistance of CSF shunt catheters as they age, altering flow dynamics. In addition, the use of straight connectors within a CSF shunt system increases the resistance to flow of artificial CSF within the shunt system. The increase in resistance appears to be related to the duration of implantation and the length of the catheter and inversely related to the diameter of the catheter. This increase in resistance may be related to sterile shunt malfunction. The addition of straight connectors is associated with a significant increase in resistance in comparison with catheters without connectors (p = 0.005). PMID- 22295927 TI - Natural history and imaging prevalence of cavernous malformations in children and young adults. AB - OBJECT: This study was undertaken to define the age-related prevalence of cavernous malformations (CMs) in children and young adults undergoing intracranial imaging. In addition, the authors aim to clarify the natural history of CMs in young people, especially in those with incidentally discovered lesions. METHODS: To identify those patients with CMs, the authors retrospectively reviewed the electronic medical records of 14,936 consecutive patients 25 years of age or younger who had undergone brain MR imaging. In patients with a CM, clinical and imaging data were collected. Patients with untreated cavernomas who had more than 6 months of clinical and MR imaging follow-up were included in a natural history analysis. The natural history analysis included 110 CMs in 56 patients with a 3.5-year mean clinical follow-up interval (199 patient-years and 361 cavernoma-years). RESULTS: In 92 patients (0.6%), 164 CMs were identified. The imaging prevalence of cavernomas increased with advancing age (p = 0.002). Multiple CMs occurred in 28 patients (30%), and 8 patients (9%) had a family history of multiple CMs. Fifty patients (54%) presented with symptoms related to the cavernoma, of whom 30 presented with hemorrhage (33%). Of the 164 cavernomas identified, 103 (63%) were considered incidental, asymptomatic lesions. Larger size was associated with acute symptomatic presentation (p = 0.0001). During the follow-up interval, 6 patients with 8 cavernomas developed 11 symptomatic hemorrhages after initial identification. Five of the patients who had a hemorrhage during the follow-up interval had initially presented with hemorrhage, while only 1 had presented incidentally. The hemorrhage rate for all patients in the natural history group was 1.6% per patient-year and 0.9% per cavernoma-year. The hemorrhage rate was 8.0% per patient-year in the symptomatic group versus 0.2% in the incidental group. Symptomatic hemorrhage after long-term follow-up was associated with initial acute presentation (p = 0.02). CONCLUSIONS: The imaging prevalence of CM increases with advancing age during childhood. Patients presenting without hemorrhage have a significantly lower risk of bleeding compared with those who present with acute neurological symptoms. Comparing this series of children to prior analyses of CM natural history in adults, the authors' data do not suggest a higher bleeding risk in younger patients. PMID- 22295928 TI - Colloid cyst of velum interpositum: a rare finding. AB - The authors present the case of a child with a colloid cyst of the velum interpositum. To the best of the authors' knowledge, this is the first reported case in the pediatric literature and only the second reported case to date. The patient was of an 11-year-old boy in whom this lesion was found after a minor head injury. He had a 6-month history of memory deficits. A lesion consistent with a colloid cyst was seen in the region of the velum interpositum, in the roof of the third ventricle. This lesion was excised successfully via a transcallosal interfornical approach. There were no new postoperative deficits and the child made a full recovery of time. PMID- 22295929 TI - Effects of intrathecal baclofen therapy on motor and cognitive functions in a rat model of cerebral palsy. AB - OBJECT: Cerebral palsy (CP) arises in the early stages of brain development and manifests as spastic paresis that is often associated with cognitive dysfunction. Available CP treatments are aimed at the management of spasticity and include botulinum toxin administration, selective dorsal rhizotomy, and intrathecal baclofen (ITB). In this study, the authors investigated whether the management of spasticity with ITB therapy affected motor function and whether the release of spasticity was associated with an improvement in intellectual function. METHODS: Newborn Sprague-Dawley rats were divided into the following groups: control, CP model, and CP model with ITB therapy. For the CP model, postnatal Day 7 (P7) rats were exposed to hypoxic conditions (8% O(2)) for 150 minutes after ligation of the right common carotid artery. In the groups receiving ITB therapy, a spinal catheter was connected to an osmotic pump filled with baclofen and placed in the spinal subarachnoid space on P21 in the early group and on P35 in the late group. A daily dose of 12 MUg of baclofen was continuously administered until P49, resulting in 28 days of therapy in the early group and 14 days in the late group. Changes in spasticity in the CP and CP with ITB treatment groups were confirmed by assessing the motor evoked potential in the plantar muscle. RESULTS: In the CP group, the time required to complete a beam-walking test on P49 was significantly longer than that in the control and ITB treatment groups (4.15 +/- 0.60 vs 2.10 +/- 0.18 and 2.22 +/- 0.22 seconds, respectively). Results of the beam-walking test are expressed as the mean +/- SD. Radial arm maze performance on P49 indicated that spatial reference memory had significantly deteriorated in the CP group compared with controls (2.33 +/- 0.87 vs 0.86 +/- 0.90 points); moreover, working memory was also negatively affected by CP (0.78 +/- 1.09 vs 0.14 +/- 0.38 points). Results of the memory tests are expressed as the mean +/- SE. These memory functions did not recover after ITB treatment. CONCLUSIONS: Management of spasticity with ITB therapy improved the walking ability in the rat CP model. Intrathecal baclofen therapy-which reduces harmful sensory and motor stimulations caused by spasticity to more optimal levels-contributed to motor function recovery; however, it had no effect on intellectual recovery as assessed by memory performance in the rat CP model. PMID- 22295930 TI - Cerebrospinal fluid leaks. PMID- 22295931 TI - Ventriculogastric shunt. PMID- 22295933 TI - Comparison of serum and lithium-heparinate plasma for the accurate measurements of endogenous and exogenous morphine concentrations. PMID- 22295934 TI - Pilot 24 month study to compare mycophenolate mofetil and tacrolimus in the treatment of membranous lupus nephritis with nephrotic syndrome. AB - AIM: This pilot study compared mycophenolate mofetil (MMF) and tacrolimus (Tac) in the treatment of severe membranous lupus nephritis (MLN). METHOD: This was a 24 month prospective, randomized, open-label multi-centre exploratory study on Chinese patients with biopsy-proven pure Class V MLN with nephrotic syndrome. Patients were randomized to treatment with either MMF or Tac, both in combination with prednisolone and the efficacy and tolerability outcomes were examined. RESULTS: Sixteen patients were included, seven in the MMF and nine in the Tac treatment arm. At 24 months the complete response, partial response and overall response rates were 57.1% vs. 11.1% (P = 0.049), 14.3% vs. 44.4% (P = 0.197) and 71.4% vs. 55.6% (P = 0.515) in the MMF and Tac groups, respectively. The two groups had similar reduction of proteinuria and longitudinal profiles of serum albumin and creatinine levels. Serum creatinine remained stable in both groups, except in two patients who had a transient increase associated with high Tac blood levels. Adverse events in the MMF group included herpes zoster in one patient and reversible leucopenia in another, while in the Tac group four patients had severe infections and one developed new onset diabetes. No relapse occurred during the study period. CONCLUSION: Both MMF and Tac when combined with corticosteroids are effective treatment options for severe MLN. PMID- 22295936 TI - Physical disintegration of toilet papers in wastewater systems: experimental analysis and mathematical modeling. AB - Physical disintegration of representative toilet papers was investigated in this study to assess their disintegration potential in sewer systems. Characterization of toilet papers from different parts of the world indicated two main categories as premium and average quality. Physical disintegration experiments were conducted with representative products from each category according to standard protocols with improvements. The experimental results were simulated by mathematical model to estimate best-fit values of disintegration rate coefficients and fractional distribution ratios. Our results from mathematical modeling and experimental work show that premium products release more amounts of small fibers and disintegrate more slowly than average ones. Comparison of the toilet papers with the tampon applicators studied previously indicates that premium quality toilet papers present significant potential to persist in sewer pipes. Comparison of turbulence level in our experimental setup with those of partial flow conditions in sewer pipes indicates that drains and small sewer pipes are critical sections where disintegration of toilet papers will be limited. For improvement, requirements for minimum pipe slopes may be increased to sustain transport and disintegration of flushable products in small pipes. In parallel, toilet papers can be improved to disintegrate rapidly in sewer systems, while they meet consumer expectations. PMID- 22295937 TI - Psychosocial and cultural correlates of depression among Hispanic men with HIV infection: a pilot study. AB - Depression is a common mental health condition among persons with human immunodeficiency virus (HIV) infection. Depression influences quality of life, social relationships and adherence to medication therapy. Little is known about depression among Hispanic men with HIV infection. The purpose of this pilot study was to describe the relationships of depression to other psychosocial factors (self-esteem, Hispanic stress, substance abuse and violence) and cultural factors (familism and Hispanic stress) among a sample of Hispanic men with HIV infection. Using a cross-sectional, descriptive research design a convenience sample of 46 Hispanic men with HIV infection was recruited and surveyed from the South Florida area of the USA. The majority of the participants (65%; n = 30) were depressed. In addition, the majority of participants reported high familism and self-esteem and low Hispanic stress. A history of substance abuse and childhood and adult violence were common. Significant relationships were noted between depression, and self-esteem, Hispanic stress, substance abuse, and adult physical violence. Healthcare providers need to be aware of the high rates of depression, substance abuse and violence that may occur among Hispanic men with HIV infection. More research is needed to further explore the relationship of these factors, as well as to determine the impact that these variables have on adherence to medication therapy among Hispanic men with HIV infection. PMID- 22295938 TI - Ketamine analgesia: a call for better science. PMID- 22295939 TI - The impact of intra-aortic balloon pump weaning protocols on in-hospital clinical outcomes. AB - BACKGROUND: Current literature recommends weaning intra-aortic balloon pump (IABP) support prior to discontinuation. To date, no studies have compared various weaning strategies for safety or efficacy. This study was designed to evaluate the impact of weaning on in-hospital clinical outcomes. METHODS: From 5/1/07 through 5/1/09 429 patients receiving IABP therapy were retrospectively identified using CPT1 billing codes. The study population and clinical outcomes analysis were stratified by use of weaning protocols versus immediate discontinuation of the IABP. In a subset analysis the patients receiving weaning protocols prior to IABP discontinuation were stratified for further analysis of clinical outcomes by whether they had received 1:3 ratio counterpulsation during their wean or whether they only received 1:2 counterpulsation prior to IABP discontinuation. These groups were analyzed for differences in primary and secondary end-points. RESULTS: Of the 429 patients identified, 344 (80.2%) were weaned prior to IABP discontinuation and 85 (19.8%) of the patients had their IABP abruptly discontinued. Patients not weaned had a lower heart rate after IABP discontinuation than those weaned, but no difference in systolic and mean blood pressure or urine output. There was no significant difference in mortality. Weaning was associated with a nonsignificant trend toward increased length of stay. CONCLUSIONS: This study suggests that weaning protocols offer no hemodynamic benefits or improvement in in-hospital mortality rates. Weaning is associated with trend toward increased length of stay. We conclude that weaning offers no advantage over direct device removal and would advocate that balloon pumps be directly withdrawn when counterpulsation is terminated. PMID- 22295940 TI - Kinetic isotope effects for Cl + CH4 ? HCl + CH3 calculated using ab initio semiclassical transition state theory. AB - Calculations were carried out for 25 isotopologues of the title reaction for various combinations of (35)Cl, (37)Cl, (12)C, (13)C, (14)C, H, and D. The computed rate constants are based on harmonic vibrational frequencies calculated at the CCSD(T)/aug-cc-pVTZ level of theory and X(ij) vibrational anharmonicity coefficients calculated at the CCSD(T) /aug-cc-pVDZ level of theory. For some reactions, anharmonicity coefficients were also computed at the CCSD(T)/aug-cc pVTZ level of theory. The classical reaction barrier was taken from Eskola et al. [J. Phys. Chem. A 2008, 112, 7391-7401], who extrapolated CCSD(T) calculations to the complete basis set limit. Rate constants were calculated for temperatures from ~100 to ~2000 K. The computed ab initio rate constant for the normal isotopologue is in good agreement with experiments over the entire temperature range (~10% lower than the recommended experimental value at 298 K). The ab initio H/D kinetic isotope effects (KIEs) for CH(3)D, CH(2)D(2), CHD(3), and CD(4) are in very good agreement with literature experimental data. The ab initio (12)C/(13)C KIE is in error by ~2% at 298 K for calculations using X(ij) coefficients computed with the aug-cc-pVDZ basis set, but the error is reduced to ~1% when X(ij) coefficients computed with the larger aug-cc-pVTZ basis set are used. Systematic improvements appear to be possible. The present SCTST results are found to be more accurate than those from other theoretical calculations. Overall, this is a very promising method for computing ab initio kinetic isotope effects. PMID- 22295942 TI - Gordon M. Cragg, D.Phil., D.Sc. (h.c.): a man for all natural products. PMID- 22295943 TI - Neck compartmentalization as the molecular basis for the different endocytic behaviour of Chs3 during budding or hyperpolarized growth in yeast cells. AB - Yeast cells normally grow by budding, but under certain specific conditions they are also able to grow in hyperpolarized forms reminiscent of hyphal growth. During vegetative growth, the synthesis of the septum that physically separates yeast cells during cytokinesis depends on the correct assembly of the septin ring. Septins and actin patches are assembled at the neck, forming two concentric rings where the actin patch ring occupies the external-most part. This specific positioning defines a plasma membrane region at the neck from which other lateral membrane compartments are excluded. In this scenario, correct assembly of the chitin ring is dependent on the anchoring of Chs3 to the septin ring through Chs4. The anchoring of Chs3 to septins through Chs4 prevents the arrival of this protein at endocytic sites, thus reducing the endocytosis of Chs3. This allows an equilibrium to be set up between the antero- and retrograde transport of Chs3, facilitating the synthesis of the chitin ring at the neck. In contrast, hyperpolarized growth is characterized by a reduced endocytic turnover of Chs3, which in turn lead to the accumulation of Chs3 at the plasma membrane and a concomitant increase in chitin synthesis. PMID- 22295944 TI - Apolipoprotein A-I amyloidogenic variant L174S, expressed and isolated from stably transfected mammalian cells, is associated with fatty acids. AB - Sixteen variants of apolipoprotein A-I (ApoA-I) are associated with hereditary systemic amyloidoses, characterized by amyloid deposition in peripheral organs of patients. As these are heterozygous for the amyloidogenic variants, their isolation from plasma is impracticable and recombinant expression systems are needed. Here we report the expression of recombinant ApoA-I amyloidogenic variant Leu174 with Ser (L174S) in stably transfected Chinese hamster ovary-K1 cells. ApoA-I variant L174S was found to be efficiently secreted in the culture medium, from which it was isolated following a one-step purification procedure. Mass spectrometry analyses allowed the qualitative and quantitative definition of the amyloidogenic variant lipid content, which was found to consist of two saturated and two monounsaturated fatty acids. Interestingly, the same lipid species were found to be associated with the wild-type ApoA-I, expressed and isolated using the same cell system, with lower values of the lipid to protein molar ratios with respect to the amyloidogenic variant. A possible role of fatty acids in trafficking and secretion of apolipoproteins may be hypothesized. PMID- 22295946 TI - The effects of four different stroke patterns on manual wheelchair propulsion and upper limb muscle strain. AB - PURPOSE: To evaluate the effects of stroke pattern on handrim biomechanics and upper limb electromyography (EMG) in experienced wheelchair users. METHOD: Subjects propelled their own wheelchair on a level, motor-driven treadmill using each of four identified stroke patterns: arcing, double loop (DL), semi-circular (SC) and single loop (SL). Upper limb EMG and measurements taken from an instrumented wheelchair wheel were compared for each pattern. A one-way ANOVA with Bonferroni correction (p < 0.05) was used to check for significant differences. RESULTS: The DL and SC patterns produced the best overall results. The DL pattern led to a significantly longer contact angle and significantly less braking moment than the SL and arcing patterns, and a significantly lower cadence than the SL pattern. The SC pattern led to a significantly longer contact angle than the SL pattern and the lowest peak force and impact of any pattern. There were no significant differences in integrated EMG (IEMG); however, the DL and arcing patterns produced lower combined IEMG values. CONCLUSIONS: When traversing level terrain, wheelchair users should push with either the DL or SC patterns. Between the two, the DL pattern required less muscle activity and may be a better choice for experienced wheelchair users. PMID- 22295945 TI - Nuclear inelastic scattering and Mossbauer spectroscopy as local probes for ligand binding modes and electronic properties in proteins: vibrational behavior of a ferriheme center inside a beta-barrel protein. AB - In this work, we present a study of the influence of the protein matrix on its ability to tune the binding of small ligands such as NO, cyanide (CN(-)), and histamine to the ferric heme iron center in the NO-storage and -transport protein Nitrophorin 2 (NP2) from the salivary glands of the blood-sucking insect Rhodnius prolixus. Conventional Mossbauer spectroscopy shows a diamagnetic ground state of the NP2-NO complex and Type I and II electronic ground states of the NP2-CN(-) and NP2-histamine complex, respectively. The change in the vibrational signature of the protein upon ligand binding has been monitored by Nuclear Inelastic Scattering (NIS), also called Nuclear Resonant Vibrational Spectroscopy (NRVS). The NIS data thus obtained have also been calculated by quantum mechanical (QM) density functional theory (DFT) coupled with molecular mechanics (MM) methods. The calculations presented here show that the heme ruffling in NP2 is a consequence of the interaction with the protein matrix. Structure optimizations of the heme and its ligands with DFT retain the characteristic saddling and ruffling only if the protein matrix is taken into account. Furthermore, simulations of the NIS data by QM/MM calculations suggest that the pH dependence of the binding of NO, but not of CN(-) and histamine, might be a consequence of the protonation state of the heme carboxyls. PMID- 22295948 TI - pH-programmable DNA logic arrays powered by modular DNAzyme libraries. AB - Nature performs complex information processing circuits, such the programmed transformations of versatile stem cells into targeted functional cells. Man-made molecular circuits are, however, unable to mimic such sophisticated biomachineries. To reach these goals, it is essential to construct programmable modular components that can be triggered by environmental stimuli to perform different logic circuits. We report on the unprecedented design of artificial pH programmable DNA logic arrays, constructed by modular libraries of Mg(2+)- and UO(2)(2+)-dependent DNAzyme subunits and their substrates. By the appropriate modular design of the DNA computation units, pH-programmable logic arrays of various complexities are realized, and the arrays can be erased, reused, and/or reprogrammed. Such systems may be implemented in the near future for nanomedical applications by pH-controlled regulation of cellular functions or may be used to control biotransformations stimulated by bacteria. PMID- 22295949 TI - Effects of genetic variation in the P2RX7 gene on pharmacodynamics of a P2X(7) receptor antagonist: a prospective genotyping approach. AB - AIMS: To investigate the effects of two single nucleotide polymorphisms (SNPs) in the human P2X7 receptor gene (P2RX7)--1068G>A (A348T) and 1513A>C (E496A)--on P2X7 receptor function, using a specific receptor antagonist (GSK1370319A) and prospective genetic stratification. METHODS: Lipopolysaccharide- and ATP stimulated interleukin-1beta production was determined in the presence or absence of GSK1370319A in blood culture from 32 prospectively genotyped subjects. RESULTS: There was approximately 6.7-fold difference (P < 0.0001) in IC50 for inhibition of ATP-stimulated interleukin-1beta release by GSK1370319A between individuals with the homozygous gain--(1068A) and loss-of-function (1513C) genotypes (expressing the 348T, 496E and 348A, 496A alleles, respectively). CONCLUSIONS: Leukocyte P2X7 receptors had significantly altered pharmacodynamic responses to a specific antagonist (GSK1370319A), directly related to SNP genotype. PMID- 22295950 TI - Factor analysis of the French version of the shorter 12-item Perception of Aggression Scale (POAS) and of a new modified version of the Overt Aggression Scale (MOAS). AB - Psychiatric staff perceptions of aggression by psychiatric patients may affect the therapeutic relationship between care providers and patients in institutions. Attitudes to and the subjective experience of violence may also differ substantially between members of a single care team. This study seeks to validate the French versions of scales of staff attitudes to and subjective experience of institutional violence: a new, modified version of the Overt Aggression Scale (MOAS) to measure the subjective perception of the frequency of aggression in the ward; and the Perception of Aggression Scale (POAS) to assess attitudes to the expression of violence by psychiatric patients. Frontline staff (n = 362) from eight French-language psychiatric institutions in the province of Quebec were surveyed. Factor analyses were performed to determine the validity of the French language MOAS and POAS. As expected, a four-factor structure emerged for the MOAS. For the 12-item POAS, a three-factor structure was found: (1) 'Aggression as a dysfunctional/undesirable phenomenon'; (2) 'Aggression as a positive expression'; and (3) 'Aggression as a protective measure'. This study supports use of the French MOAS and POAS in assessing staff attitudes to and subjective experience of aggression in future projects to explore the perception and management of inpatient violence. PMID- 22295951 TI - Evaluating the performance of different procedures for constructing confidence intervals for coefficient alpha: a simulation study. AB - Reliability is one of the most important aspects of testing in educational and psychological measurement. The construction of confidence intervals for reliability coefficients has important implications for evaluating the accuracy of the sample estimate of reliability and for comparing different tests, scoring rubrics, or training procedures for raters or observers. The present simulation study evaluated and compared various parametric and non-parametric methods for constructing confidence intervals of coefficient alpha. Six factors were manipulated: number of items, number of subjects, population coefficient alpha, deviation from essentially parallel condition, item response distribution and type. The coverage and width of different confidence intervals were compared across simulation conditions. PMID- 22295952 TI - The beneficial effect of topical glycopyrrolate in a patient with neuropathic lower extremity pain. PMID- 22295941 TI - Gold nanoparticles in chemical and biological sensing. PMID- 22295953 TI - Biomarkers of endothelial dysfunction in patients with primary focal segmental glomerulosclerosis. AB - AIM: Endothelial dysfunction occurs in nephrotic syndrome (NS) and may constitute a link between NS and vascular complications. Focal segmental glomerulosclerosis (FSGS) is a common cause of NS. This study aimed to assess endothelial markers at different stages of FSGS and define whether they were associated with thromboembolic complications and disease activity. METHODS: Forty-four patients with nephrotic-range proteinuria and biopsy-proven primary FSGS were included in this study. Nine of them had concurrent thromboembolisms. Thirty-two sex- and age matched healthy volunteers served as controls. Endothelial markers including circulating endothelial cells (CECs), soluble thrombomodulin (sTM), von Willebrand factor (vWf), soluble vascular cell adhesion molecule-1 (sVCAM-1) and sE-selectin were assessed at the commencement of the study in all participants and were repeated at 2, 6 and 12 months of follow-up in patients without thromboembolisms. RESULTS: Patients with FSGS during active stage showed significantly higher levels of CECs, sTM, vWf, sVCAM-1 and sE-selectin when compared with controls. Moreover, patients with thromboembolisms had higher CECs and vWf than those without thromboembolisms. In patients without thromboembolisms, endothelial markers except sE-selectin had inverse correlations with serum albumin and were positively related to cholesterol. Multiple analyses showed that cholesterol and serum albumin were independent predictors of CECs and sTM, and vWf and sVCAM-1, respectively. At follow-up, these markers systematically decreased as the disease went into remission, but the increase in vWf and sVCAM-1 persisted even in patients obtaining complete remission for nearly a year. In patients with no response, levels of endothelial markers exhibited no obvious change. CONCLUSION: Patients with FSGS had elevated markers of endothelial dysfunction, which were largely related to the activity of the disease. Meanwhile, levels of CECs and vWf were higher in patients concurrent with thromboembolisms. PMID- 22295955 TI - Respirable aerosols from fluidized bed coal combustion. 3. Elemental composition of fly ash. PMID- 22295954 TI - beta-methasone-containing biodegradable poly(lactide-co-glycolide) acid microspheres for intraarticular injection: effect of formulation parameters on characteristics and in vitro release. AB - A sustained drug release system based on the injectable poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with beta-methasone was prepared for localized treatment of rheumatic arthritis. The microscopy and structure of microspheres were characterized by scanning electron microscope (SEM) and Fourier transform infrared (FTIR). The effects of various formulation parameters on the properties of microspheres and in vitro release pattern of beta-methasone were also investigated. The results demonstrated that increase in drug/polymer ratio led to increased particle size as well as drug release rate. Increase in PLGA concentration led to increased particle size, but decreased burst release. The drug encapsulation efficiency increased sharply by increasing polyvinyl alcohol (PVA) concentration in the aqueous phase from 1.5 to 2.0%. beta-methasone release rate decreased considerately with decreasing OP (organic phase)/AP (aqueous phase) volume ratio. Stirring rate had significantly influence on the particle size and encapsulation efficiency. Independent of formulation parameters, beta methasone was slowly released from the PLGA microspheres over 11 days. The drug release profile of high drug loaded microspheres agree with Higuchi equation with a release mechanism of diffusion and erosion, that of middle drug loaded microspheres best agreed with Hixcon-Crowell equation and controlled by diffusion and erosion as well. The low drug loaded microspheres well fitted to logarithm normal distribution equation with mechanism of purely Fickian diffusion. PMID- 22295956 TI - Cross-linkage between anilines and phenolic humus constituents. PMID- 22295957 TI - Dihaloacetonitriles in drinking water: algae and fulvic acid as precursors. PMID- 22295958 TI - Kinetics of the reaction between hydrofluoric acid and calcium oxide for fluoride emission control. PMID- 22295959 TI - Thermal and metabolic factors affecting PCB uptake by adult brown trout. PMID- 22295960 TI - Correlation of the ozone formation rates with hydroxyl radical concentrations in the propylene-nitrogen oxide dry air system: effective ozone formation rate constant. PMID- 22295961 TI - Laboratory evaluation of an airborne ozone instrument that compensates for altitude/sensitivity effects. PMID- 22295962 TI - Effect of nutrients on the rates of mineralization of trace concentrations of phenol and p-nitrophenol. PMID- 22295963 TI - Environmental fate and effects of ethylene oxide. PMID- 22295964 TI - Smog chamber studies of nitrogen oxide (NOx) transformation rate and nitrate precursor relationships. PMID- 22295966 TI - Notes. Biofouling control with ferrate(VI). PMID- 22295965 TI - Notes. Effect of decreased use of lead in gasoline on the soil of a highway. PMID- 22295967 TI - Notes. Cross-contamination of water samples taken for analysis of purgeable organic compounds. PMID- 22295968 TI - Notes. A simple and inexpensive method for measuring integrated light energy. PMID- 22295970 TI - Temperature dependence and interferences of NO and N2O microelectrodes used in wastewater treatment. AB - Electrodes for nitric and nitrous oxide have been on the market for some time, but have not yet been tested for an application in wastewater treatment processes. Both sensors were therefore assessed with respect to their (non)linear response, temperature dependence and potential cross sensitivity to dissolved compounds, which are present and highly dynamic in nitrogen conversion processes (nitric oxide, nitrous oxide, nitrogen dioxide, ammonia, hydrazine, hydroxylamine, nitrous acid, oxygen, and carbon dioxide). Off-gas measurements were employed to differentiate between cross sensitivity to interfering components and chemical nitric oxide or nitrous oxide production. Significant cross sensitivities were detected for both sensors: by the nitrous oxide sensor to nitric oxide and by the nitric oxide sensor to ammonia, hydrazine, hydroxylamine and nitrous acid. These interferences could, however, be removed by correction functions. Temperature fluctuations in the range of +/-1 degrees C lead to artifacts of +/-3.5% for the nitric oxide and +/-3.9% for the nitrous oxide sensor and can be corrected with exponential equations. The results from this study help to significantly shorten and optimize the determination of the correction functions and are therefore relevant for all users of nitric and nitrous oxide electrodes. PMID- 22295971 TI - An ab initio study of the E 3Pig state of the iodine molecule. AB - The E (3)Pi(g) state of the iodine molecule is studied by ab initio multireference methods coupled with effective core potentials and large basis sets. Two potential minima are found, a global featuring an ion-pair character, and a local presenting a purely Rydberg nature. Four avoided crossings along the dissociation coordinate attribute an interesting topology to its potential energy curve, and their effect on the vibrational levels of I(2) is discussed. PMID- 22295972 TI - Interleukin-6 receptor alpha is co-localised with melanin-concentrating hormone in human and mouse hypothalamus. AB - Interleukin (IL)-6 deficient mice develop mature-onset obesity. Furthermore, i.c.v. administration of IL-6 increases energy expenditure, suggesting that IL-6 centrally regulates energy homeostasis. To investigate whether it would be possible for IL-6 to directly influence the energy homeostasis via hypothalamic regulation in humans and rodents, we mapped the distribution of the ligand binding IL-6 receptor alpha (IL-6Ralpha) in this brain region. In the human hypothalamus, IL-6Ralpha-immunoreactivity was detected in perikarya and first order dendrites of neurones. The IL-6Ralpha-immunoreactive (-IR) neurones were observed posterior to the level of the interventricular foramen. There, IL 6Ralpha-IR neurones were located in the lateral hypothalamic, perifornical, dorsal and posterior hypothalamic areas, the hypothalamic dorsomedial nucleus and in the zona incerta. In the caudal part of the hypothalamus, the density of the IL-6Ralpha-IR neurones gradually increased. Double-labelling immunofluorescent studies demonstrated that IL-6Ralpha immunoreactivity was localised in the same neurones as the orexigenic neuropeptide, melanin-concentrating hormone (MCH). By contrast, IL-6Ralpha-immunoreactivity was not observed in the orexin B-IR neurones. To determine whether the observed expression of IL-6Ralpha is evolutionary conserved, we studied the co-localisation of IL-6Ralpha with MCH and orexin in the mouse hypothalamus, where IL-6Ralpha-immunoreactivity was present in numerous MCH-IR and orexin-IR neurones. Our data demonstrate that the MCH neurones of the human hypothalamus, as well as the MCH and orexin neurones of the mouse hypothalamus, contain IL-6Ralpha. This opens up the possibility that IL-6 influences the energy balance through the MCH neurones in humans, and both MCH and orexin neurones in mice. PMID- 22295973 TI - Is HbA1c a risk factor for type 2 diabetic subjects without macro and micro vascular complications? AB - OBJECTIVE: Our study attempted to evaluate the diagnostic value of HbA1c in predicting diabetic dyslipidemia and cardiovascular diseases (CVD). METHODS: Study comprised 229 subjects (156 males and 73 females) with diabetic dyslipidemia without any micro and macro vascular disorders. Fasting blood samples were taken to analyse biochemical parameters like HbA1c, sugar and lipid profile. RESULTS: The HbA1c levels did not differ much between males (6.96 +/- 1.11) and females (7.01 +/- 1.19). HbA1c demonstrated a positive significant correlation with cholesterol, LDL and a negative significant correlation with HDL. Patients with HbA1c >7.0% had significantly higher value of cholesterol, LDL when compared with <7.0%. CONCLUSIONS: The findings of this study clearly suggest that HbA1c endures the ability of predicting CVD risk in the diabetic patients without any micro and macro vascular disorder. Therefore study recommends using HbA1c as a marker for predicting the risk of developing CVD. PMID- 22295974 TI - Electrocatalytic hydrogen redox chemistry on gold nanoparticles. AB - Electrocatalytic proton reduction leading to the formation of adsorbed molecular hydrogen on gold nanoparticles of 1-3 and 14-16 nm diameter stabilized by 1 mercapto-undecane-11-tetra(ethyleneglycol) has been demonstrated by cyclic voltammetry using a hanging mercury drop electrode. The nanoparticles were adsorbed to the electrode from aqueous dispersion and formed robust surface layers transferrable to fresh base electrolyte solutions. Unique electrocatalytic proton redox chemistry was observed that has no comparable counterpart in the electrochemistry of bulk gold electrodes. Depending on size, the nanoparticles have a discrete number of electrocatalytically active sites for the two electron/two-proton reduction process. The adsorbed hydrogen formed is oxidized with the reverse potential sweep. These findings represent a new example of qualitative different behavior of nanoparticles in comparison with the corresponding bulk material. PMID- 22295975 TI - Lipid body biogenesis and the role of microtubules in lipid synthesis in Ornithogalum umbellatum lipotubuloids. AB - Lipid bodies present in lipotubuloids of Ornithogalum umbellatum ovary epidermis take the form of a lens between leaflets of ER (endoplasmic reticulum) membrane filled with a highly osmiophilic substance. The two enzymes, DGAT1 [DAG (diacylglycerol) acyltransferase 1] and DGAT2 (DAG acyltransferase 2), involved in this process are synthesized on rough ER and localized in the ER near a monolayer surrounding entities like lipid bodies. After reaching the appropriate size, newly formed lipid bodies transform into mature spherical lipid bodies filled with less osmiophilic content. They appear to be surrounded by a half-unit membrane, with numerous microtubules running adjacently in different directions. The ER, no longer continuous with lipid bodies, makes contact with them through microtubules. At this stage, lipid synthesis takes place at the periphery of lipid bodies. This presumption, and a hypothesis that microtubules are involved in lipid synthesis delivering necessary components to lipid bodies, is based on strong arguments: (i) silver grains first appear over microtubules after a short [3H]palmitic acid incubation and before they are observed over lipid bodies; (ii) blockade of [3H]palmitic acid incorporation into lipotubuloids by propyzamide, an inhibitor of microtubule function; and (iii) the presence of gold grains above the microtubules after DGAT1 and DGAT2 reactions, as also near microtubules after an immunogold method that identifies phospholipase D1. PMID- 22295976 TI - Evaluation of a self-assessed screening test for masticatory ability of Taiwanese older adults. AB - OBJECTIVES: The aim of this study was to evaluate a screening test based on a food intake questionnaire to discriminate the masticatory ability of Taiwanese older adults with 20 and more natural teeth and at least 8 functional tooth units (FTUs) from the masticatory ability of those with fewer than 20 natural teeth and 8 FTUs. MATERIALS AND METHODS: The subjects were 2244 patients (mean age, 60.4+/ 10.0 years) recruited from 23 counties and cities in Taiwan. Information about their demographic data, dentition, and masticatory ability was collected. Masticatory ability was measured for 23 food groups comprising 35 common Taiwanese foods, and receiver operation characteristic curve analysis was performed. RESULTS: The results showed that the final questionnaire included 14 food groups and a subject choosing 'difficult to eat' responses for 4 and more of these food groups had the same masticatory ability as individuals with fewer than 20 natural teeth and 8 FTUs. CONCLUSION: In conclusion, foods that are the most difficult to eat are not necessarily good discriminatory indicators. Hence, the 14-food group questionnaire can be considered the best screening test for masticatory ability of Taiwanese older adults in terms of the presence of 20 and more natural teeth and at least 8 FTUs. PMID- 22295977 TI - In vitro NADH-oxidase, NADPH-oxidase and myeloperoxidase activity of macrophages after Tinospora cordifolia (guduchi) treatment. AB - It is believed that the enhanced microbicidal and tumoricidal capability of activated macrophages is related to the remarkable increase in the production of oxygen metabolites. Both the production of H2O2 and the oxidation of NAD(P)H are directly dependent upon NAD(P)H-oxidase. It has been established that the respiratory burst is due to activation of NAD(P)H-oxidase localised in the plasmalemma. Myeloperoxidase is believed to be involved in augmenting the cytotoxic activity of H2O2. It was observed that the macrophage cell line J774A.1 when treated with Tinospora cordifolia (guduchi) and LPS showed enhanced NADH oxidase, NADPH-oxidase and myeloperoxidase production as compared to macrophages treated with medium alone. The direct drug treatment to J774A cells showed activation as assessed by biochemical assays. These results suggest that high NADH-oxidase, NADPH-oxidase and myeloperoxidase activities may account for tumoricidal and microbicidal properties via macrophage activation. PMID- 22295978 TI - The computational power of interactive recurrent neural networks. AB - In classical computation, rational- and real-weighted recurrent neural networks were shown to be respectively equivalent to and strictly more powerful than the standard Turing machine model. Here, we study the computational power of recurrent neural networks in a more biologically oriented computational framework, capturing the aspects of sequential interactivity and persistence of memory. In this context, we prove that so-called interactive rational- and real weighted neural networks show the same computational powers as interactive Turing machines and interactive Turing machines with advice, respectively. A mathematical characterization of each of these computational powers is also provided. It follows from these results that interactive real-weighted neural networks can perform uncountably many more translations of information than interactive Turing machines, making them capable of super-Turing capabilities. PMID- 22295979 TI - Learning coefficient of generalization error in Bayesian estimation and vandermonde matrix-type singularity. AB - The term algebraic statistics arises from the study of probabilistic models and techniques for statistical inference using methods from algebra and geometry (Sturmfels, 2009 ). The purpose of our study is to consider the generalization error and stochastic complexity in learning theory by using the log-canonical threshold in algebraic geometry. Such thresholds correspond to the main term of the generalization error in Bayesian estimation, which is called a learning coefficient (Watanabe, 2001a , 2001b ). The learning coefficient serves to measure the learning efficiencies in hierarchical learning models. In this letter, we consider learning coefficients for Vandermonde matrix-type singularities, by using a new approach: focusing on the generators of the ideal, which defines singularities. We give tight new bound values of learning coefficients for the Vandermonde matrix-type singularities and the explicit values with certain conditions. By applying our results, we can show the learning coefficients of three-layered neural networks and normal mixture models. PMID- 22295980 TI - Generalization and multirate models of motor adaptation. AB - When subjects adapt their reaching movements in the setting of a systematic force or visual perturbation, generalization of adaptation can be assessed psychophysically in two ways: by testing untrained locations in the work space at the end of adaptation (slow postadaptation generalization) or by determining the influence of an error on the next trial during adaptation (fast trial-by-trial generalization). These two measures of generalization have been widely used in psychophysical studies, but the reason that they might differ has not been addressed explicitly. Our goal was to develop a computational framework for determining when a two-state model is justified by the data and to explore the implications of these two types of generalization for neural representations of movements. We first investigated, for single-target learning, how well standard statistical model selection procedures can discriminate two-process models from single-process models when learning and retention coefficients were systematically varied. We then built a two-state model for multitarget learning and showed that if an adaptation process is indeed two-rate, then the postadaptation generalization approach primarily probes the slow process, whereas the trial-by-trial generalization approach is most informative about the fast process. The fast process, due to its strong sensitivity to trial error, contributes predominantly to trial-by-trial generalization, whereas the strong retention of the slow system contributes predominantly to postadaptation generalization. Thus, when adaptation can be shown to be two-rate, the two measures of generalization may probe different brain representations of movement direction. PMID- 22295981 TI - Reduction from cost-sensitive ordinal ranking to weighted binary classification. AB - We present a reduction framework from ordinal ranking to binary classification. The framework consists of three steps: extracting extended examples from the original examples, learning a binary classifier on the extended examples with any binary classification algorithm, and constructing a ranker from the binary classifier. Based on the framework, we show that a weighted 0/1 loss of the binary classifier upper-bounds the mislabeling cost of the ranker, both error wise and regret-wise. Our framework allows not only the design of good ordinal ranking algorithms based on well-tuned binary classification approaches, but also the derivation of new generalization bounds for ordinal ranking from known bounds for binary classification. In addition, our framework unifies many existing ordinal ranking algorithms, such as perceptron ranking and support vector ordinal regression. When compared empirically on benchmark data sets, some of our newly designed algorithms enjoy advantages in terms of both training speed and generalization performance over existing algorithms. In addition, the newly designed algorithms lead to better cost-sensitive ordinal ranking performance, as well as improved listwise ranking performance. PMID- 22295982 TI - Statistical mechanics of reward-modulated learning in decision-making networks. AB - The neural substrates of decision making have been intensively studied using experimental and computational approaches. Alternative-choice tasks accompanying reinforcement have often been employed in investigations into decision making. Choice behavior has been empirically found in many experiments to follow Herrnstein's matching law. A number of theoretical studies have been done on explaining the mechanisms responsible for matching behavior. Various learning rules have been proved in these studies to achieve matching behavior as a steady state of learning processes. The models in the studies have consisted of a few parameters. However, a large number of neurons and synapses are expected to participate in decision making in the brain. We investigated learning behavior in simple but large-scale decision-making networks. We considered the covariance learning rule, which has been demonstrated to achieve matching behavior as a steady state (Loewenstein & Seung, 2006 ). We analyzed model behavior in a thermodynamic limit where the number of plastic synapses went to infinity. By means of techniques of the statistical mechanics, we can derive deterministic differential equations in this limit for the order parameters, which allow an exact calculation of the evolution of choice behavior. As a result, we found that matching behavior cannot be a steady state of learning when the fluctuations in input from individual sensory neurons are so large that they affect the net input to value-encoding neurons. This situation naturally arises when the synaptic strength is sufficiently strong and the excitatory input and the inhibitory input to the value-encoding neurons are balanced. The deviation from matching behavior is caused by increasing variance in the input potential due to the diffusion of synaptic efficacies. This effect causes an undermatching phenomenon, which has been often observed in behavioral experiments. PMID- 22295983 TI - Reinforcement-based decision making in corticostriatal circuits: mutual constraints by neurocomputational and diffusion models. AB - In this letter, we examine the computational mechanisms of reinforce-ment-based decision making. We bridge the gap across multiple levels of analysis, from neural models of corticostriatal circuits-the basal ganglia (BG) model (Frank, 2005 , 2006 ) to simpler but mathematically tractable diffusion models of two choice decision making. Specifically, we generated simulated data from the BG model and fit the diffusion model (Ratcliff, 1978 ) to it. The standard diffusion model fits underestimated response times under conditions of high response and reinforcement conflict. Follow-up fits showed good fits to the data both by increasing nondecision time and by raising decision thresholds as a function of conflict and by allowing this threshold to collapse with time. This profile captures the role and dynamics of the subthalamic nucleus in BG circuitry, and as such, parametric modulations of projection strengths from this nucleus were associated with parametric increases in decision boundary and its modulation by conflict. We then present data from a human reinforcement learning experiment involving decisions with low- and high-reinforcement conflict. Again, the standard model failed to fit the data, but we found that two variants similar to those that fit the BG model data fit the experimental data, thereby providing a convergence of theoretical accounts of complex interactive decision-making mechanisms consistent with available data. This work also demonstrates how to make modest modifications to diffusion models to summarize core computations of the BG model. The result is a better fit and understanding of reinforcement-based choice data than that which would have occurred with either model alone. PMID- 22295984 TI - Stochastic perturbation methods for spike-timing-dependent plasticity. AB - Online machine learning rules and many biological spike-timing-dependent plasticity (STDP) learning rules generate jump process Markov chains for the synaptic weights. We give a perturbation expansion for the dynamics that, unlike the usual approximation by a Fokker-Planck equation (FPE), is well justified. Our approach extends the related system size expansion by giving an expansion for the probability density as well as its moments. We apply the approach to two observed STDP learning rules and show that in regimes where the FPE breaks down, the new perturbation expansion agrees well with Monte Carlo simulations. The methods are also applicable to the dynamics of stochastic neural activity. Like previous ensemble analyses of STDP, we focus on equilibrium solutions, although the methods can in principle be applied to transients as well. PMID- 22295985 TI - Entropy estimation in Turing's perspective. AB - A new nonparametric estimator of Shannon's entropy on a countable alphabet is proposed and analyzed against the well-known plug-in estimator. The proposed estimator is developed based on Turing's formula, which recovers distributional characteristics on the subset of the alphabet not covered by a size-n sample. The fundamental switch in perspective brings about substantial gain in estimation accuracy for every distribution with finite entropy. In general, a uniform variance upper bound is established for the entire class of distributions with finite entropy that decays at a rate of O(ln(n)/n) compared to O([ln(n)]2/n) for the plug-in. In a wide range of subclasses, the variance of the proposed estimator converges at a rate of O(1/n), and this rate of convergence carries over to the convergence rates in mean squared errors in many subclasses. Specifically, for any finite alphabet, the proposed estimator has a bias decaying exponentially in n. Several new bias-adjusted estimators are also discussed. PMID- 22295986 TI - Dynamical synapses enhance neural information processing: gracefulness, accuracy, and mobility. AB - Experimental data have revealed that neuronal connection efficacy exhibits two forms of short-term plasticity: short-term depression (STD) and short-term facilitation (STF). They have time constants residing between fast neural signaling and rapid learning and may serve as substrates for neural systems manipulating temporal information on relevant timescales. This study investigates the impact of STD and STF on the dynamics of continuous attractor neural networks and their potential roles in neural information processing. We find that STD endows the network with slow-decaying plateau behaviors: the network that is initially being stimulated to an active state decays to a silent state very slowly on the timescale of STD rather than on that of neuralsignaling. This provides a mechanism for neural systems to hold sensory memory easily and shut off persistent activities gracefully. With STF, we find that the network can hold a memory trace of external inputs in the facilitated neuronal interactions, which provides a way to stabilize the network response to noisy inputs, leading to improved accuracy in population decoding. Furthermore, we find that STD increases the mobility of the network states. The increased mobility enhances the tracking performance of the network in response to time-varying stimuli, leading to anticipative neural responses. In general, we find that STD and STP tend to have opposite effects on network dynamics and complementary computational advantages, suggesting that the brain may employ a strategy of weighting them differentially depending on the computational purpose. PMID- 22295987 TI - Learning invariance from natural images inspired by observations in the primary visual cortex. AB - The human visual system has the remarkable ability to largely recognize objects invariant of their position, rotation, and scale. A good interpretation of neurobiological findings involves a computational model that simulates signal processing of the visual cortex. In part, this is likely achieved step by step from early to late areas of visual perception. While several algorithms have been proposed for learning feature detectors, only few studies at hand cover the issue of biologically plausible learning of such invariance. In this study, a set of Hebbian learning rules based on calcium dynamics and homeostatic regulations of single neurons is proposed. Their performance is verified within a simple model of the primary visual cortex to learn so-called complex cells, based on a sequence of static images. As a result, the learned complex-cell responses are largely invariant to phase and position. PMID- 22295988 TI - Intracerebroventricular opioids for intractable pain. AB - When pain is refractory to systemic opioid and non-opioid analgesic therapy and palliative chemoradiation or ablative or stimulant neurosurgical procedures are not possible, palliative treatment becomes limited, particularly if the patient wishes to be at home at the end of life. Intracerebroventricular (ICV) infusion of morphine in the home setting might be presented as an option. The present article reviews the basic and clinical evidence of the efficacy and safety of ICV administration of opioids. Information was gathered from various bibliographic sources, including PubMed and others, and summarized and evaluated to assess the efficacy and safety of ICV opioids for pain relief. Results from ICV infusion of morphine into terminally ill patients refractory to other pain treatments have been reported since the early 1980s. Good efficacy has been achieved for the vast majority of patients, without serious development of analgesic tolerance. There have also been a low incidence of adverse effects, such as constipation and respiratory depression, and a significant retention of alertness associated with this route of administration. Intracerebroventricular infusion of opioid analgesics thus appears to be a safe and effective therapy for the palliative treatment of refractory pain. PMID- 22295989 TI - Increased 25-hydroxycholesterol concentrations in the lungs of patients with chronic obstructive pulmonary disease. AB - BACKGROUND AND OBJECTIVE: 25-Hydroxycholesterol (25-HC) is produced from cholesterol by the enzyme cholesterol 25-hydroxylase and is associated with atherosclerosis of vessels. Recently, 25-HC was reported to cause inflammation in various types of tissues. The aim of this study was to assess the production of 25-HC in the airways and to elucidate the role of 25-HC in neutrophil infiltration in the airways of patients with chronic obstructive pulmonary disease (COPD). METHODS: Eleven control never-smokers, six control ex-smokers without COPD and 13 COPD patients participated in the lung tissue study. The expression of cholesterol 25-hydroxylase in the lung was investigated. Twelve control subjects and 17 patients with COPD also participated in the sputum study. The concentrations of 25-HC in sputum were quantified by liquid chromatography/mass spectrometry/mass spectrometry analysis. To elucidate the role of 25-HC in neutrophilic inflammation of the airways, the correlation between 25-HC levels and neutrophil counts in sputum was investigated. RESULTS: The expression of cholesterol 25-hydroxylase was significantly enhanced in lung tissue from COPD patients compared with that from control subjects. Cholesterol 25-hydroxylase was localized in alveolar macrophages and pneumocytes of COPD patients. The concentration of 25-HC in sputum was significantly increased in COPD patients and was inversely correlated with percent of predicted forced vital capacity, forced expiratory volume in 1 s and diffusing capacity of carbon monoxide. The concentrations of 25-HC in sputum were significantly correlated with sputum interleukin-8 levels and neutrophil counts. CONCLUSIONS: 25-HC production was enhanced in the airways of COPD patients and may play a role in neutrophilic inflammation. PMID- 22295990 TI - Enhanced thermoelectric properties of solution grown Bi2Te(3-x)Se(x) nanoplatelet composites. AB - We report on the enhanced thermoelectric properties of selenium (Se) doped bismuth telluride (Bi(2)Te(3-x)Se(x)) nanoplatelet (NP) composites synthesized by the polyol method. Variation of the Se composition within NPs is demonstrated by X-ray diffraction and Raman spectroscopy. While the calculated lattice parameters closely follow the Vegard's law, a discontinuity in the shifting of the high frequency (E(g)(2) and A(1g)(2)) phonon modes illustrates a two mode behavior for Bi(2)Te(3-x)Se(x) NPs. The electrical resistivity (rho) of spark plasma sintered pellet composites shows metallic conduction for pure Bi(2)Te(3) NP composites and semiconducting behavior for intermediate Se compositions. The thermal conductivity (kappa) for all NP composites is much smaller than the bulk values and is dominated by microstructural grain boundary scattering. With temperature dependent electrical and thermal transport measurements, we show that both the thermoelectric power S (-259 MUV/K) and the figure of merit ZT (0.54) are enhanced by nearly a factor of 4 for SPS pellets of Bi(2)Te(2.7)Se(0.3) in comparison to Bi(2)Te(3) NP composites. Tentatively, such an enhancement of the thermoelectric performance in nanoplatelet composites is attributed to the energy filtering of low energy electrons by abundant grain boundaries in aligned nanocomposites. PMID- 22295991 TI - Enhanced activity and selectivity of carbon nanofiber supported Pd catalysts for nitrite reduction. AB - Pd-based catalyst treatment represents an emerging technology that shows promise to remove nitrate and nitrite from drinking water. In this work we use vapor grown carbon nanofiber (CNF) supports in order to explore the effects of Pd nanoparticle size and interior versus exterior loading on nitrite reduction activity and selectivity (i.e., dinitrogen over ammonia production). Results show that nitrite reduction activity increases by 3.1-fold and selectivity decreases by 8.0-fold, with decreasing Pd nanoparticle size from 1.4 to 9.6 nm. Both activity and selectivity are not significantly influenced by Pd interior versus exterior CNF loading. Consequently, turnover frequencies (TOFs) among all CNF catalysts are similar, suggesting nitrite reduction is not sensitive to Pd location on CNFs nor Pd structure. CNF-based catalysts compare favorably to conventional Pd catalysts (i.e., Pd on activated carbon or alumina) with respect to nitrite reduction activity and selectivity, and they maintain activity over multiple reduction cycles. Hence, our results suggest new insights that an optimum Pd nanoparticle size on CNFs balances faster kinetics with lower ammonia production, that catalysts can be tailored at the nanoscale to improve catalytic performance for nitrite, and that CNFs hold promise as highly effective catalyst supports in drinking water treatment. PMID- 22295993 TI - Importance of interfaces in governing thermal transport in composite materials: modeling and experimental perspectives. AB - Thermal management in polymeric composite materials has become increasingly critical in the air-vehicle industry because of the increasing thermal load in small-scale composite devices extensively used in electronics and aerospace systems. The thermal transport phenomenon in these small-scale heterogeneous systems is essentially controlled by the interface thermal resistance because of the large surface-to-volume ratio. In this review article, several modeling strategies are discussed for different length scales, complemented by our experimental efforts to tailor the thermal transport properties of polymeric composite materials. Progress in the molecular modeling of thermal transport in thermosets is reviewed along with a discussion on the interface thermal resistance between functionalized carbon nanotube and epoxy resin systems. For the thermal transport in fiber-reinforced composites, various micromechanics based analytical and numerical modeling schemes are reviewed in predicting the transverse thermal conductivity. Numerical schemes used to realize and scale the interface thermal resistance and the finite mean free path of the energy carrier in the mesoscale are discussed in the frame of the lattice Boltzmann-Peierls Callaway equation. Finally, guided by modeling, complementary experimental efforts are discussed for exfoliated graphite and vertically aligned nanotubes based composites toward improving their effective thermal conductivity by tailoring interface thermal resistance. PMID- 22295994 TI - Ewing sarcoma: clinical state-of-the-art. AB - Ewing sarcoma, a rare malignancy of childhood and adolescence, has become a model of advances in diagnosis, treatment, and outcome through long-standing research efforts in multinational clinical trials. With modern multimodal regimens consisting of local surgery and/or radiotherapy plus intensive systemic chemotherapy, survival can be achieved for ~ 70% of patients with localized disease. However, in the last decade, improvement in survival curves has slowed down. Also, a relapse rate of ~ 30% remains unacceptable, since salvage strategies for Ewing sarcoma recurrence are discouraging and prognosis is unfavorable in most cases. Metastatic disease at diagnosis poses a similar challenge, since even if remission is achieved, relapse frequently occurs despite the most intensive treatment. Urgently needed, novel biology-driven treatment options are now beginning to emerge on the horizon, but have not yet reached the standard of care. An overview of the current clinical state-of-the-art is provided in this article. PMID- 22295995 TI - Mental health nurse independent prescribing: what are nurse prescribers' views of the barriers to implementation? AB - This paper reports a pilot study exploring mental health nurse prescribers' perceptions of barriers to prescribing independently but also includes perceptions of barriers to supplementary prescribing. Current prescribing practice as experienced by mental health nurses suggests a need to identify and highlight these barriers. A mixed methodology explanatory sequential study was carried out over 3 months in Scotland in 2008 as part of a Master's degree. A questionnaire was completed by 33 mental health nurse prescribers. A focus group was conducted with 12 mental health nurse prescribers. Participants' views exposed a number of barriers to prescribing previously unidentified in a review of the relevant literature, and concurred with some previously documented barriers. Sixty per cent of mental health nurse prescribers in the study were not prescribing. Barriers identified in the study included concern about how prescribing impacts on the therapeutic relationship, role conflict, lack of support, inappropriateness of prescriber training, remuneration, qualifying to prescribing time, supervision, prescribing policies, clinical governance and nurse management. Nurse prescribing involves increased accountability and responsibility which is not currently recognized in job status or pay banding. Mental health nurse prescribing has the potential to enhance service provision, but until barriers to prescribing have been identified and addressed as part of the process of organizational change, nurse prescribing cannot achieve its maximum potential. PMID- 22295996 TI - Cytochrome P450 11A1 bioactivation of a kinase inhibitor in rats: use of radioprofiling, modulation of metabolism, and adrenocortical cell lines to evaluate adrenal toxicity. AB - A drug candidate, BMS-A ((N-(4-((1H-pyrrolo[2,3-b]pyridin-4-yl)oxy)-3 fluorophenyl)-1-(4-fluorophenyl) 2-oxo-1,2-dihydropyridine- 3-carboxamide)), was associated with dose- and time-dependent vacuolar degeneration and necrosis of the adrenal cortex following oral administration to rats. Pretreatment with 1 aminobenzotriazole (ABT), a nonspecific P450 inhibitor, ameliorated the toxicity. In vivo and in vitro systems, including adrenal cortex-derived cell lines, were used to study the mechanism responsible for the observed toxicity. Following an oral dose of the C-14 labeled compound, two hydroxylated metabolites of the parent (M2 and M3) were identified as prominent species found only in adrenal glands and testes, two steroidogenic organs. In addition, a high level of radioactivity was covalently bound to adrenal tissue proteins, 40% of which was localized in the mitochondrial fraction. ABT pretreatment reduced localization of radioactivity in the adrenal gland. Low levels of radioactivity bound to proteins were also observed in testes. Both M3 and covalent binding to proteins were found in incubations with mitochondrial fraction isolated from adrenal tissue in the presence of NADPH. In vitro formation of M3 and covalent binding to proteins were not affected by addition of GSH or a CYP11B1/2 inhibitor, metyrapone (MTY), but were inhibited by ketoconazole (KTZ) and a CYP11A1 inhibitor, R-(+) aminoglutethimide (R-AGT). BMS-A induced apoptosis in a mouse adrenocortical cell line (Y-1) but not in a human cell line (H295R). Metabolite M3 and covalent binding to proteins were also produced in Y-1 and to a lesser extent in H295R cells. The cell toxicity, formation of M3, and covalent binding to proteins were all diminished by R-AGT but not by MTY. These results are consistent with a CYP11A1-mediated bioactivation to generate a reactive species, covalent binding to proteins, and subsequently rat adrenal toxicity. The thorough understanding of the metabolism-dependent adrenal toxicity was useful to evaluate cross-species adrenal toxicity potential of this compound and related analogues. PMID- 22295997 TI - Implementing evidence-based practice in the reality of clinical practice. PMID- 22295998 TI - Infrared matrix isolation study of the thermal and photochemical reactions of ozone with dimethylcadmium. AB - The matrix isolation technique has been combined with infrared spectroscopy and theoretical calculations to explore the reaction of (CH(3))(2)Cd with O(3) over a range of time scales and upon irradiation. During twin jet deposition, multiple novel product species were observed along with several stable "late" products. Following annealing of these matrices to 35 K, absorptions due to two novel product species increased in intensity. In addition, new bands appeared, indicating the formation of an additional product. Subsequent UV irradiation destroyed several of the initial products and produced a new photoproduct. On the basis of (18)O and (16,18)O spectroscopic data and theoretical calculations, the novel intermediates H(3)COCdCH(3), H(3)CCdCH(2)OH, H(3)COCdOOCH(3), and H(3)CCdCHO were identified. Merged jet deposition led to a number of stable "late" products, including H(2)CO, CH(3)OH, and C(2)H(6), identifications that were confirmed by (18)O substitution. Mechanistic inferences for this reaction are discussed. PMID- 22296000 TI - Guest Editorial: A farewell-not a goodbye. PMID- 22296001 TI - Letters. Laboratory testing. PMID- 22296002 TI - Letters. January editorial. PMID- 22296003 TI - Letters. Environmental achievement prize. PMID- 22296004 TI - Currents. PMID- 22296005 TI - Water reuse: Where are we headed? PMID- 22296006 TI - Deactivation of hazardous chemical wastes. PMID- 22296008 TI - Predicting future pollution exceedances under emission controls. PMID- 22296007 TI - Legislative outlook on environmental issues. PMID- 22296009 TI - Detailed model for the mobility of arsenic in lacustrine sediments based on measurements in Lake Ohakuri. PMID- 22296010 TI - Field measurements of particle dry deposition rates to foliage and inert surfaces in a forest canopy. PMID- 22296011 TI - Kinetics of the gas-phase reactions of the hydroxyl radical with naphthalene, phenanthrene, and anthracene. PMID- 22296012 TI - Mutagenic activity of irradiated toluene nitrogen oxide (NOx)/water/air mixtures. PMID- 22296013 TI - Thermodynamics of the hydrogen peroxide-water system. PMID- 22296014 TI - Size distributions of ammonium nitrate and sodium nitrate in atmospheric aerosols. PMID- 22296015 TI - Reaction kinetics of nitrogen dioxide with methanol in the gas phase. PMID- 22296016 TI - Atmospheric chemistry of cis- and trans-3-hexene-2,5-dione. PMID- 22296017 TI - Ames assay chromatograms of extracts of diesel exhaust particles from heavy-duty trucks on the road and from passenger cars on a dynamometer. PMID- 22296018 TI - Scanning electron microscopy and energy-dispersive x-ray spectroscopy analysis of submicrometer coal fly ash particles. PMID- 22296019 TI - Anaerobic degradation of trichloroethylene in soil. PMID- 22296020 TI - Gas-phase hydrogenolysis of polychlorobiphenyls. PMID- 22296021 TI - .alpha.-Tocopheryl acetate as an indicator of municipal waste contamination in the environment. PMID- 22296023 TI - Kinetics of monobromamine disporportionation dibromamine formation in aqueous ammonia solutions. PMID- 22296022 TI - Comment on "Kinetics of monobromamine disproportionation-dibromamine formation in aqueous ammonia solutions". PMID- 22296024 TI - Proteomic analysis of cerebrospinal fluid from obese women with idiopathic intracranial hypertension: a new approach for identifying new candidates in the pathogenesis of obesity. AB - Body weight control is tightly regulated in the hypothalamus. The inaccessibility of human brain tissue can be partially solved by using cerebrospinal fluid (CSF) as a tool for assessing the central nervous system's production of orexigen and anorexigen factors. Using proteomic analysis, the present study investigated the differentially displayed proteins in human CSF from obese and non-obese subjects. We designed a case-control study conducted in a reference hospital where eight obese (cases) and eight non-obese (controls) women with idiopathic intracranial hypertension were included. Intracranial hypertension was normalised through the placement of a ventriculo- or lumboperitoneal shunt in the 12 months before their inclusion in the study. Isotope-coded protein label (for proteins > 10 kDa) and label-free liquid chromatography (for proteins < 10 kDa) associated with mass spectrometry analysis were used. Eighteen differentially expressed proteins were identified. Many of them fall into three main groups: inflammation (osteopontin, fibrinogen gamma and beta chain, alpha1 acid glycoprotein 2 and haptoglobin), neuroendocrine mediators (neurosecretory protein VGF, neuroendocrine protein 7B2, chromogranin-A and chromogranin B), and brain plasticity (testican-1, isoform 10 of fibronectin, galectin-3 binding protein and metalloproteinase inhibitor type 2). The differential production of osteopontin, neurosecretory protein VGF, chromogranin-A and fibrinogen gamma chain was further confirmed by either enzyme linked immunosorbent assay or western blotting. In conclusion, we have identified potential candidates that could be involved in the pathogenesis of obesity. Further studies aiming to investigating the precise role of these proteins in the pathogenesis of obesity and their potential therapeutic implications are needed. PMID- 22296025 TI - Maintenance of low sodium and high potassium levels in cells and in tendon/collagen. AB - Mammalian cells have a higher concentration of potassium and a lower concentration of sodium than their extracellular environment. The mechanisms responsible for the unequal distribution of these ions are commonly ascribed to the presence of an energy requiring plasma membrane ATPase pump, and the presence of membrane channels that pass one ion selectively, while excluding others. This report deals with other mechanisms that might explain this heterogeneous distribution of ions. To study other mechanisms, we turned to a non-living system, specifically tendon/collagen to eliminate the contribution of the membrane pump and channels. A simple gravimetric method was designed to measure solute accumulation or exclusion during rehydration of a well-washed, carefully dried and well-characterized protein specimen (tendon/collagen). Exposure to physiological salt concentrations resulted in selective exclusion of Na+ over K+, whereas exposure to low-salt concentration resulted in accumulation of these solutes. It is postulated that this solute redistribution occurs in all hydrated proteins and is partially responsible for the heterogeneous solute distribution in cells presently assigned to pump and channel mechanisms. Physical and thermodynamic mechanisms are offered to explain the observed heterogeneous solute distributions. PMID- 22296026 TI - On quantitative determination of volatile organic compound concentrations using proton transfer reaction time-of-flight mass spectrometry. AB - Proton transfer reaction - mass spectrometry (PTR-MS) has become a reference technique in environmental science allowing for VOC monitoring with low detection limits. The recent introduction of time-of-flight mass analyzer (PTR-ToF-MS) opens new horizons in terms of mass resolution, acquisition time, and mass range. A standard procedure to perform quantitative VOC measurements with PTR-ToF-MS is to calibrate the instrument using a standard gas. However, given the number of compounds that can be simultaneously monitored by PTR-ToF-MS, such a procedure could become impractical, especially when standards are not readily available. In the present work we show that, under particular conditions, VOC concentration determinations based only on theoretical predictions yield good accuracy. We investigate a range of humidity and operating conditions and show that theoretical VOC concentration estimations are accurate when the effect of water cluster ions is negligible. We also show that PTR-ToF-MS can successfully be used to estimate reaction rate coefficients between H(3)O(+) and VOC at PTR-MS working conditions and find good agreement with the corresponding nonthermal theoretical predictions. We provide a tabulation of theoretical rate coefficients for a number of relevant volatile organic compounds at various energetic conditions and test the approach in a laboratory study investigating the oxidation of alpha pinene. PMID- 22296027 TI - Position-specific chemical modification and quantitative proteomics disclose protein orientation adsorbed on silica nanoparticles. AB - We describe a method for determining the orientation of cytochrome c, RNase A, and lysozyme on silica nanoparticles (SNPs) using chemical modification combined with proteolysis-mass spectrometry. The proteins interacted with SNPs through preferential adsorption sites, which are dependent on SNP diameter; 4 nm SNPs induce greater structural stabilization than 15 nm particles, presumably due to greater surface curvature of the former. These results suggest that nanoparticle size and protein structure influence protein orientation on SNPs. PMID- 22296028 TI - News from the Biological Stain Commission no. 12. AB - In this 12(th) issue of News from the Biological Stain Commission (BSC) under the heading of Regulatory affairs, the Biological Stain Commission's International Affairs Committee presents information from the meetings of ISO/TC 212/WG 1 Quality and competence in the medical laboratory and ISO/TC 212/WG 3 In vitro diagnostic products both held on 2 - 3 June 2010, plus information on the second plenary meeting of ISO/TC 212 Clinical laboratory testing and in vitro diagnostic test systems held on 4 June 2010. All meetings took place in Seoul, Republic of Korea. Finally, information is provided concerning the 25(th) meeting of CEN/TC 140 In vitro diagnostic medical devices held on 23 June 2010 in Berlin, Germany. PMID- 22296029 TI - Penny wise, pound foolish? Coverage limits on immunosuppression after kidney transplantation. PMID- 22296030 TI - Colloidal synthesis of wurtzite Cu2ZnSnS4 nanorods and their perpendicular assembly. AB - The quaternary copper chalcogenide Cu(2)ZnSnS(4) is an important emerging material for the development of low-cost and sustainable solar cells. Here we report a facile solution synthesis of stoichiometric Cu(2)ZnSnS(4) in size controlled nanorod form (11 nm * 35 nm). The monodisperse nanorods have a band gap of 1.43 eV and can be assembled into perpendicularly aligned arrays by controlled evaporation from solution. PMID- 22296031 TI - Safety of anti-TNFalpha agents in the treatment of psoriasis and psoriatic arthritis. AB - CONTEXT: The efficacy and favorable safety profile of anti-tumor necrosis factor (TNF) agents in the treatment of psoriasis and psoriatic arthritis (PsA) are supported by several randomized controlled studies and meta-analyses. However, some concerns on the long-term safety of these drugs still exist, as these studies generally included small patient numbers and were performed in selected patient populations. OBJECTIVE: This review presents and discusses current evidence on the safety of anti-TNFalpha agents in patients with psoriasis and PsA, with a focus on European registry studies and case reports of particular importance. METHODS: Key studies on the safety of anti-TNFalpha agents in the treatment of adult patients with psoriasis or PsA were identified by a MEDLINE search (last updated 10 November 2011) based on several interrelated queries, with a focus on European registries. Other studies and case reports were included if deemed relevant. Studies concerning other conditions, such as rheumatoid arthritis (RA), were included as appropriate when data in psoriatic disease were unavailable or insufficient. RESULTS: Available data on the safety of anti TNFalpha agents such as etanercept in psoriasis and PsA appear reassuring, even if some concerns still exist. Most notably, data suggest a higher incidence of infection and lymphoma amongst patients treated with the anti-TNFalpha monoclonal antibodies infliximab and adalimumab compared with etanercept. CONCLUSION: The overall safety profile of monoclonal antibodies in patients with psoriasis, PsA and RA seems less favorable than that of etanercept, particularly in terms of risk of infection and hepatotoxicity. PMID- 22296033 TI - The prevalence and predictors of airway hyperresponsiveness in sarcoidosis. AB - BACKGROUND AND OBJECTIVE: Obstructive airflow limitation is the most common physiological impairment in sarcoidosis. This study determined the prevalence of airway hyperresponsiveness (AHR) in sarcoidosis, the correlation between responses to direct (using histamine) and indirect (using hypertonic saline) bronchial challenge, and the clinical, physiological and radiological predictors of AHR. METHODS: Subjects with sarcoidosis and a baseline forced expiratory volume in 1 s (FEV(1)) >35% predicted underwent hypertonic and histamine challenge, lung function testing and high resolution computed tomography (HRCT) of the chest. AHR was defined as a 15% fall in FEV(1) to hypertonic saline and a 20% fall in FEV(1) to histamine. RESULTS: The 52 subjects had well-preserved lung function (FEV(1) = 2.8 +/- 0.7 L, 87% predicted). AHR was detected in 5/47 (11%) to hypertonic saline and 19/43 (44%) to histamine challenge. On univariate analysis, response to histamine challenge was predicted by conglomerate fibrosis (P = 0.02) and reticular pattern (P = 0.03) on HRCT. The baseline % predicted forced expiratory volume in 1 s was significantly inversely associated with AHR on univariate (P = 0.004) and multivariate analysis (P = 0.01) when adjusted by HRCT patterns. CONCLUSIONS: The higher prevalence of AHR using histamine challenge than hypertonic saline challenge and the association with baseline % predicted FEV(1) suggest that the AHR in sarcoidosis may reflect the consequences of airway remodelling following inflammation. PMID- 22296034 TI - NeuroD1 A45T and PAX4 R121W polymorphisms are associated with plasma glucose level of repaglinide monotherapy in Chinese patients with type 2 diabetes. AB - AIMS: We aimed to determine whether NeuroD1/BETA2 and PAX4 polymorphisms were associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetes mellitus (T2DM) patients. METHODS: Three hundred and sixty-eight T2DM patients and 132 healthy control subjects were genotyped by restriction fragment length polymorphism. Forty-three patients with various genotypes were randomly selected to undergo 8 weeks of repaglinide treatment (3 mg day(-1)). Fasting plasma glucose, postprandial plasma glucose, glycated haemoglobin, fasting and postprandial serum insulin (FINS, PINS), homeostasis model assessment for insulin resistance, serum triglyceride, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein-cholesterol were determined before and after repaglinide treatment. RESULTS: The allelic frequency of NeuroD1/BETA2 T45 was higher in T2DM patients than in the control subjects [13.45 vs. 6.82%, P < 0.01, odds ratios = 2.342 (1.365, 4.019), P= 0.002]. Type 2 diabetes mellitus patients with the mutated allele of NeuroD1/BETA2 A45T polymorphism showed higher FINS (13.46 +/- 12.57 vs. 10.04 +/- 7.09 mU l(-1) , P < 0.05) (11.67, 14.83 vs. 8.38, 11.37) and PINS (52.11 +/- 40.93 vs. 68.66 +/- 43.87 mU l(-1), P < 0.05) (44.89, 58.35 vs. 55.35, 88.87) than individuals with the T allele. The PAX4 R121W R allele carriers had higher PINS (52.11 +/- 40.93 vs. 68.66 +/- 43.87 mU l(-1), P < 0.05) (44.89, 58.35 vs. 55.35, 88.87) than subjects with the W allele. After repaglinide treatment, patients with the T allele of NeuroD1/BETA2 A45T polymorphisms had attenuated efficacy on fasting plasma glucose (-2.79 +/- 2.14 vs.-0.99 +/- 1.80 mmol l(-1), P < 0.01) (-3.53, -1.84 vs.-1.99, -0.13) and postprandial plasma glucose (-6.71 +/- 5.90 vs.-2.54 +/- 3.39 mmol l(-1), P < 0.01) (-9.28, -4.62 vs.-4.34, -0.84). Patients with the RR genotype of PAX4 R121W showed better efficacy with respect to the level of postprandial plasma glucose than R/W genotypes (-6.53 +/- 6.52 vs.-2.95 +/- 1.17 mmol l(-1), P < 0.05) ( 8.20, -4.89 vs.-3.92, -1.20). CONCLUSIONS: The NeuroD1/BETA2 and PAX4 polymorphisms were substantially associated with plasma glucose level after repaglinide monotherapy. PMID- 22296035 TI - Postoperative headache following acoustic neuroma resection: occipital nerve injuries are associated with a treatable occipital neuralgia. AB - OBJECTIVE: To demonstrate that occipital nerve injury is associated with chronic postoperative headache in patients who have undergone acoustic neuroma excision and to determine whether occipital nerve excision is an effective treatment for these headaches. BACKGROUND: Few previous reports have discussed the role of occipital nerve injury in the pathogenesis of the postoperative headache noted to commonly occur following the retrosigmoid approach to acoustic neuroma resection. No studies have supported a direct etiologic link between the two. The authors report on a series of acoustic neuroma patients with postoperative headache presenting as occipital neuralgia who were found to have occipital nerve injuries and were treated for chronic headache by excision of the injured nerves. METHODS: Records were reviewed to identify patients who had undergone surgical excision of the greater and lesser occipital nerves for refractory chronic postoperative headache following acoustic neuroma resection. Primary outcomes examined were change in migraine headache index, change in number of pain medications used, continued use of narcotics, patient satisfaction, and change in quality of life. Follow-up was in clinic and via telephone interview. RESULTS: Seven patients underwent excision of the greater and lesser occipital nerves. All met diagnostic criteria for occipital neuralgia and failed conservative management. Six of 7 patients experienced pain reduction of greater than 80% on the migraine index. Average pain medication use decreased from 6 to 2 per patient; 3 of 5 patients achieved independence from narcotics. Six patients experienced 80% or greater improvement in quality of life at an average follow-up of 32 months. There was one treatment failure. Occipital nerve neuroma or nerve entrapment was identified during surgery in all cases where treatment was successful but not in the treatment failure. CONCLUSION: In contradistinction to previous reports, we have identified a subset of patients in whom the syndrome of postoperative headache appears directly related to the presence of occipital nerve injuries. In patients with postoperative headache meeting diagnostic criteria for occipital neuralgia, occipital nerve excision appears to provide relief of the headache syndrome and meaningful improvement in quality of life. Further studies are needed to confirm these results and to determine whether occipital nerve injury may present as headache types other than occipital neuralgia. These findings suggest that patients presenting with chronic postoperative headache should be screened for the presence of surgically treatable occipital nerve injuries. PMID- 22296036 TI - Effects of adding low levels of a disulfide reducing agent on the disulfide interactions of beta-lactoglobulin and kappa-casein in skim milk. AB - Low concentrations of a disulfide reducing agent were added to unheated and heated (80 degrees C for 30 min) skim milk, with and without added whey protein. The reduction of the beta-lactoglobulin and kappa-casein disulfide bonds was monitored over time using electrophoresis. The distribution of the proteins between the colloidal and serum phases was also investigated. kappa-Casein disulfide bonds were reduced in preference to those of beta-lactoglobulin in both unheated and heated skim milk (with or without added whey protein). In addition, in heated skim milk, while the serum kappa-casein was reduced more readily than the colloidal kappa-casein, the distribution of kappa-casein between the two phases was not affected. PMID- 22296037 TI - Quantum mechanical study of sulfuric acid hydration: atmospheric implications. AB - The role of the binary nucleation of sulfuric acid in aerosol formation and its implications for global warming is one of the fundamental unsettled questions in atmospheric chemistry. We have investigated the thermodynamics of sulfuric acid hydration using ab initio quantum mechanical methods. For H(2)SO(4)(H(2)O)(n) where n = 1-6, we used a scheme combining molecular dynamics configurational sampling with high-level ab initio calculations to locate the global and many low lying local minima for each cluster size. For each isomer, we extrapolated the Moller-Plesset perturbation theory (MP2) energies to their complete basis set (CBS) limit and added finite temperature corrections within the rigid-rotor harmonic-oscillator (RRHO) model using scaled harmonic vibrational frequencies. We found that ionic pair (HSO(4)(-).H(3)O(+))(H(2)O)(n-1) clusters are competitive with the neutral (H(2)SO(4))(H(2)O)(n) clusters for n >= 3 and are more stable than neutral clusters for n >= 4 depending on the temperature. The Boltzmann averaged Gibbs free energies for the formation of H(2)SO(4)(H(2)O)(n) clusters are favorable in colder regions of the troposphere (T = 216.65-273.15 K) for n = 1-6, but the formation of clusters with n >= 5 is not favorable at higher (T > 273.15 K) temperatures. Our results suggest the critical cluster of a binary H(2)SO(4)-H(2)O system must contain more than one H(2)SO(4) and are in concert with recent findings (1) that the role of binary nucleation is small at ambient conditions, but significant at colder regions of the troposphere. Overall, the results support the idea that binary nucleation of sulfuric acid and water cannot account for nucleation of sulfuric acid in the lower troposphere. PMID- 22296038 TI - Biological maturation, morphology, fitness, and motor coordination as part of a selection strategy in the search for international youth soccer players (age 15 16 years). AB - We report the morphology (height, weight, body fat, body mass index), fitness (strength, speed, agility, flexibility), and soccer-specific (dribbling) and non specific motor coordination skills (Korper KoordinationsTest fur Kinder; KTK) of 78 Belgian international youth soccer players aged 15-16 years with varying biological maturity status. The more mature players (U16 and U17) possessed higher morphological measures and outperformed their later maturing peers (U16 Futures and U17 Futures) on almost all fitness tests. However, soccer-specific and non-specific motor coordination tests did not distinguish the more mature players from the later maturing players in both age groups. When adjusted for the confounder (age at peak height velocity), multivariate analysis of covariance revealed that several morphology- and fitness-related parameters did not differ between selection groups, again in both age groups. These findings indicate that biological maturation affects morphology and fitness more so than motor coordination skills. In conclusion, to prevent the dropout of promising late maturing players, we suggest avoiding one-dimensional approaches and to include measures of biological maturity status as well as maturity independent performance tests during the talent identification and selection process. PMID- 22296039 TI - Massive cystic granulocytic sarcoma in a newly diagnosed patient with acute myeloid leukaemia. PMID- 22296040 TI - Correlation of Pfg377 ortholog gene expression of Plasmodium vivax and mosquito infection. AB - OBJECTIVE: To determine the expression of Pfg377 ortholog gene in Plasmodium vivax, and examine its correlation with mosquito infection. METHODS: Seventy clinical blood samples positive for P. vivax by microscopy, were used for the mosquito infectivity assay. Infectivity to female Anopheles dirus was determined from oocyst counts. The transcripts of Pfg377 ortholog gene of P. vivax from blood samples infective and non-infective to mosquitoes were examined using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Of 70 P. vivax positive blood samples, 50 (71.4%) samples were mosquito infective and 20 (28.6%) were not. In infective samples, the expression level of Pfg377 ortholog gene was significantly higher than in the non-infective group (P<0.05). In infective samples, the expression level of Pfg377 ortholog gene at >=100 copies/ml of blood cut-off point correlated with >=10 oocysts/mosquito cut off point of average oocyst numbers and with >=50% cut-off point of per cent infected mosquitoes (Pearson's chi-square correlation, P=0.014 and P=0.026, respectively). CONCLUSION: The cut-off point of the expression level of Pfg377 ortholog gene could be used to predict the infectiousness of P. vivax gametocytes leading to mosquito infection and parasite transmission in the field. PMID- 22296041 TI - It takes more than an imine: the role of the central atom on the electron accepting ability of benzotriazole and benzothiadiazole oligomers. AB - We report on the comparison of the electronic and photophysical properties of a series of related donor-acceptor-donor oligomers incorporating the previously known 2H-benzo[d][1,2,3]triazole (BTz) moiety as the acceptor and the recently reported BTzTD acceptor, a hybrid of BTz and 2,1,3-benzothiadiazole (BTD). Although often implied in the polymer literature that BTz has good acceptor character, we show that this moiety is best described as a weak acceptor. We present electrochemical, computational, and photophysical evidence supporting our assertion that BTzTD is a strong electron acceptor while maintaining the alkylation ability of the BTz moiety. Our results show that the identity of the central atom (N or S) in the benzo-fused heterocyclic ring plays an important role in both the electron-accepting and the electron-donating ability of acceptor moieties with sulfur imparting a greater electron-accepting ability and nitrogen affording greater electron-donating character. We report on the X-ray crystal structure of a BTzTD trimer, which exhibits greater local aromatic character in the region of the triazole ring and contains an electron-deficient sulfur that imparts strong electron-accepting ability. Additionally, we examine the transient absorption spectra of BTzTD and BTz oligomers and report that the BTz core promotes efficient intersystem crossing to the triplet state, while the presence of the thiadiazole moiety in BTzTD leads to a negligible triplet yield. Additionally, while BTz does not function as a good acceptor, oligomers containing this moiety do function as excellent sensitizers for the generation of singlet oxygen. PMID- 22296042 TI - Expression of inhibin/activin proteins and receptors in the human hypothalamus and basal forebrain. AB - The inhibin/activin family of proteins is known to have a broad distribution of synthesis and expression in many species, as well as a variety of functions in reproductive and other physiological systems. Yet, our knowledge regarding the production and function of inhibin and activin in the central nervous system is relatively limited, especially in humans. The present study aimed to explore the distribution of inhibin/activin protein subunits and receptors in the adult human brain. The human hypothalamus and surrounding basal forebrain was examined using post-mortem tissues from 29 adults. Immunocytochemical studies were conducted with antibodies directed against the inhibin/activin alpha, betaA, and betaB subunits, betaglycan and the activin type IIA and IIB receptors. An immunoassay was also utilised to measure dimeric inhibin A and B levels in tissue homogenates of the infundibulum of the hypothalamus. Robust betaA subunit immunoreactivity was present in the paraventricular, supraoptic, lateral hypothalamic, infundibular, dorsomedial and suprachiasmatic nuclei of the hypothalamus, in the basal ganglia, and in the nucleus basalis of Meynert. A similar staining distribution was noted for the betaB subunit, betaglycan and the type II receptor antibodies, whereas alpha subunit staining was not detected in any of the major anatomical regions of the human brain. Inhibin B immunoreactivity was present in all tissues, whereas inhibin A levels were below detectable limits. These studies show for the first time that the inhibin/activin protein subunits and receptors can be co-localised in the human brain, implicating potential, diverse neural functions. PMID- 22296043 TI - Monitoring bacterial twitter: does quorum sensing determine the behavior of water and wastewater treatment biofilms? AB - Bacteria have their own form of "twitter" communication, described as quorum sensing (QS), where bacteria emit and sense chemical signal molecules as a means to gauge population density and control gene expression. Many QS-controlled genes relate to biofilm formation and function and may be important for some water and wastewater treatment biofilms. There is a need to better understand bacterial QS, the bacteria biofilm aspects influenced by QS in engineered reactors, and to assess how designs and operations might be improved by taking this signaling into account. This paper provides a critical review of QS and how it relates to biofilms in engineered water and wastewater treatment systems and identifies needs for future research. PMID- 22296044 TI - A convenient conversion of terminal alkenes into homologous unsaturated and doubly unsaturated esters. AB - Unsaturated and doubly unsaturated esters have been synthesized in two steps by the application of a radical xanthate transfer process of a simple methylsulfoxide starting material to a range of terminal alkenes. syn-Elimination of the sulfoxide gives alpha,beta-unsaturated esters, which coupled with a xanthate elimination yields alpha,beta,gamma,delta-unsaturated esters. PMID- 22296047 TI - Letters. Pesticide residues in humans. PMID- 22296045 TI - Synthesis of pyrroles through a 4pi-electrocyclic ring-closure reaction of 1 azapentadienyl cations. AB - 1-Azapenta-1,4-diene-3-ols 4a-m are easily accessible from 1-azapenta-1,4-dien-3 ones 3a-i and organolithium compounds. Treatment of the compounds 4a-m with strong acid (triflic acid) generates 1-azapentadienyl cations in situ upon protonation at the hydroxyl oxygen atom and subsequent water elimination. The intermediate cations undergo facile 4pi-electrocyclization under ambient condition to give diversely substituted pyrroles 6a-m in moderate to good yield. The product pyrrole 6k could be characterized by X-ray diffraction. Quantum chemical calculations were performed to elucidate the mechanism of this reaction with respect to starting compounds, transition states, and products. They support the proposed mechanism of a 4pi-conrotatory Mobius-type electrocyclic ring closure reaction. PMID- 22296048 TI - Letters. Environmental fellowship program. PMID- 22296049 TI - Letters. Biodegradation of organic chemicals. PMID- 22296050 TI - Editorial: Conservation and industry: A more common agenda. PMID- 22296051 TI - Currents. PMID- 22296052 TI - Transport of organic contaminants in groundwater. PMID- 22296053 TI - CEQ's report on long-term environmental research. PMID- 22296054 TI - Analysis of polycyclic aromatic hydrocarbons in air particulate matter from a lightly industrialized urban area. PMID- 22296056 TI - Multimedia modeling of environmental transport: trichloroethylene test case. PMID- 22296055 TI - Use of solute tracers released by weathering to estimate groundwater inflow to seepage lakes. PMID- 22296057 TI - Phosphorus-zinc interactive effects on growth by Selenastrum capricornutum (Chlorophyta). PMID- 22296058 TI - High-performance size exclusion chromatography of chlorinated natural humic water and mutagenicity studies using the microscale fluctuation assay. PMID- 22296059 TI - Studies on the chlorination of chlorolignins and humic acid. PMID- 22296061 TI - Determination of total sulfur in lichens and plants by combustion-infrared analysis. PMID- 22296060 TI - Effect of ethylene and related hydrocarbons on carbon assimilation and transpiration in herbaceous and woody species. PMID- 22296062 TI - Effects of activated carbon on the reactions of free chlorine with phenols. PMID- 22296063 TI - Chemiluminescent analysis of chlorine dioxide with a membrane flow cell. PMID- 22296064 TI - Laboratory evaluation of chemical dispersants for use on oil spills at sea. PMID- 22296065 TI - Comparison of an optical particle size monitor and a cascade impactor for in stack source testing. PMID- 22296066 TI - Rate constants for the gas-phase reaction of hydroxyl radicals with biphenyl and the monochlorobiphenyls at 295 .+-. 1 K. PMID- 22296068 TI - Conscious sedation is the way forward. PMID- 22296070 TI - Role of temporary clipping in perforator damage during middle cerebral aneurysm surgery. PMID- 22296072 TI - Improving childhood vaccination rates. PMID- 22296073 TI - Keeping score under a global payment system. PMID- 22296074 TI - Opportunity in austerity--a common agenda for medicine and public health. PMID- 22296075 TI - Ulipristal acetate versus placebo for fibroid treatment before surgery. AB - BACKGROUND: The efficacy and safety of oral ulipristal acetate for the treatment of symptomatic uterine fibroids before surgery are uncertain. METHODS: We randomly assigned women with symptomatic fibroids, excessive uterine bleeding (a score of >100 on the pictorial blood-loss assessment chart [PBAC, an objective assessment of blood loss, in which monthly scores range from 0 to >500, with higher numbers indicating more bleeding]) and anemia (hemoglobin level of <=10.2 g per deciliter) to receive treatment for up to 13 weeks with oral ulipristal acetate at a dose of 5 mg per day (96 women) or 10 mg per day (98 women) or to receive placebo (48 women). All patients received iron supplementation. The coprimary efficacy end points were control of uterine bleeding (PBAC score of <75) and reduction of fibroid volume at week 13, after which patients could undergo surgery. RESULTS: At 13 weeks, uterine bleeding was controlled in 91% of the women receiving 5 mg of ulipristal acetate, 92% of those receiving 10 mg of ulipristal acetate, and 19% of those receiving placebo (P<0.001 for the comparison of each dose of ulipristal acetate with placebo). The rates of amenorrhea were 73%, 82%, and 6%, respectively, with amenorrhea occurring within 10 days in the majority of patients receiving ulipristal acetate. The median changes in total fibroid volume were -21%, -12%, and +3% (P=0.002 for the comparison of 5 mg of ulipristal acetate with placebo, and P=0.006 for the comparison of 10 mg of ulipristal acetate with placebo). Ulipristal acetate induced benign histologic endometrial changes that had resolved by 6 months after the end of therapy. Serious adverse events occurred in one patient during treatment with 10 mg of ulipristal acetate (uterine hemorrhage) and in one patient during receipt of placebo (fibroid protruding through the cervix). Headache and breast tenderness were the most common adverse events associated with ulipristal acetate but did not occur significantly more frequently than with placebo. CONCLUSIONS: Treatment with ulipristal acetate for 13 weeks effectively controlled excessive bleeding due to uterine fibroids and reduced the size of the fibroids. (Funded by PregLem; ClinicalTrials.gov number, NCT00755755.). PMID- 22296076 TI - Ulipristal acetate versus leuprolide acetate for uterine fibroids. AB - BACKGROUND: The efficacy and side-effect profile of ulipristal acetate as compared with those of leuprolide acetate for the treatment of symptomatic uterine fibroids before surgery are unclear. METHODS: In this double-blind noninferiority trial, we randomly assigned 307 patients with symptomatic fibroids and excessive uterine bleeding to receive 3 months of daily therapy with oral ulipristal acetate (at a dose of either 5 mg or 10 mg) or once-monthly intramuscular injections of leuprolide acetate (at a dose of 3.75 mg). The primary outcome was the proportion of patients with controlled bleeding at week 13, with a prespecified noninferiority margin of -20%. RESULTS: Uterine bleeding was controlled in 90% of patients receiving 5 mg of ulipristal acetate, in 98% of those receiving 10 mg of ulipristal acetate, and in 89% of those receiving leuprolide acetate, for differences (as compared with leuprolide acetate) of 1.2 percentage points (95% confidence interval [CI], -9.3 to 11.8) for 5 mg of ulipristal acetate and 8.8 percentage points (95% CI, 0.4 to 18.3) for 10 mg of ulipristal acetate. Median times to amenorrhea were 7 days for patients receiving 5 mg of ulipristal acetate, 5 days for those receiving 10 mg of ulipristal acetate, and 21 days for those receiving leuprolide acetate. Moderate-to-severe hot flashes were reported for 11% of patients receiving 5 mg of ulipristal acetate, for 10% of those receiving 10 mg of ulipristal acetate, and for 40% of those receiving leuprolide acetate (P<0.001 for each dose of ulipristal acetate vs. leuprolide acetate). CONCLUSIONS: Both the 5-mg and 10-mg daily doses of ulipristal acetate were noninferior to once-monthly leuprolide acetate in controlling uterine bleeding and were significantly less likely to cause hot flashes. (Funded by PregLem; ClinicalTrials.gov number, NCT00740831.). PMID- 22296077 TI - GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus. AB - BACKGROUND: The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes. METHODS: We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels. RESULTS: The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences. CONCLUSIONS: Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period. (Funded by Diamyd Medical and the Swedish Child Diabetes Foundation; ClinicalTrials.gov number, NCT00723411.). PMID- 22296078 TI - Clinical practice. Delayed puberty. PMID- 22296079 TI - The perpetual challenge of infectious diseases. PMID- 22296080 TI - Images in clinical medicine. Post-traumatic herniated cervical disk. PMID- 22296081 TI - Clinical problem-solving. Worth a second look. PMID- 22296082 TI - Uterine fibroids and evidence-based medicine--not an oxymoron. PMID- 22296084 TI - Timing of antiretroviral therapy for HIV-1-associated tuberculosis. PMID- 22296085 TI - Timing of antiretroviral therapy for HIV-1-associated tuberculosis. PMID- 22296087 TI - Glucocorticoids plus N-acetylcysteine in alcoholic hepatitis. PMID- 22296089 TI - Early liver transplantation for severe alcoholic hepatitis. PMID- 22296090 TI - Early liver transplantation for severe alcoholic hepatitis. PMID- 22296091 TI - Early liver transplantation for severe alcoholic hepatitis. PMID- 22296092 TI - Ultraviolet A and photosensitivity during vemurafenib therapy. PMID- 22296093 TI - Staphylococcus aureus reactivation osteomyelitis after 75 years. PMID- 22296094 TI - Images in clinical medicine. Insulin-induced lipohypertrophy. PMID- 22296096 TI - Genetic variations in loci relevant to natural killer cell function are affected by ethnicity but are generally not correlated with susceptibility to HIV-1. AB - Polymorphisms in cell surface receptors of natural killer cells and their ligands on target cells can affect susceptibility to viral infections including human immunodeficiency virus (HIV)-1. We found that the carriage of the human leukocyte antigen (HLA)-G minus 14-bp polymorphism, LILRB1 single nucleotide polymorphism rs1061680, and activating and inhibitory killer immunoglobulin-like receptors (KIRs) were different when data were compared between Caucasian, African Americans and Asian populations. However, carriage was similar when HIV-1 patients were compared with control donors, with the exception of the African American cohort. PMID- 22296097 TI - Improved clonality detection in Hodgkin lymphoma using the BIOMED-2-based heavy and kappa chain assay: a paraffin-embedded tissue study. AB - AIMS: Although BIOMED-2 polymerase chain reaction (PCR) standardization protocols allow clonality detection in nearly 100% of non-Hodgkin B cell lymphomas, they have not been widely validated for Hodgkin lymphoma (HL). Our aim was to assess BIOMED-2 protocol sensitivity when using non-microdissected, formalin-fixed, paraffin-embedded (FFPE) tissue from HL cases. METHODS AND RESULTS: We studied 69 consecutive HL cases, of which 61 corresponded to classic HL (cHL) and eight to nodular lymphocyte-predominant HL (NLPHL). CD30-positive cell numbers (<10, 10-25 or >25 per *200 field), background CD20-positive cell density (low or high) and tumour cell immunophenotype were evaluated. IGH and IGK clonality was assessed on FFPE tissue following BIOMED-2 protocols. Of the 58 assessable cHL cases, 15 (25.9%) exhibited IGH and/or IGK clonality; IGH clonality was shown by nine (15.5%) and IGK clonality by 12 (20.7%). Clonality detection rates in cHL improved as CD30-positive Reed-Sternberg (RS) cell density increased and CD20 positive B cell density decreased, although these correlations did not reach statistical significance. Of the eight NLPHL cases studied, none showed clonal rearrangement. CONCLUSIONS: Combined study of IGH and IGK rearrangement according to BIOMED-2 protocols improves clonality detection rate (up to 25% of cases) in HL, even when working on non-microdissected FFPE tissue. PMID- 22296098 TI - Is the inhaler technique associated with asthma control? PMID- 22296099 TI - Metal-free, visible-light-mediated direct C-H arylation of heteroarenes with aryl diazonium salts. AB - Visible light along with 1 mol % eosin Y catalyzes the direct C-H bond arylation of heteroarenes with aryl diazonium salts by a photoredox process. We have investigated the scope of the reaction for several aryl diazonium salts and heteroarenes. The general and easy procedure provides a transition-metal-free alternative for the formation of aryl-heteroaryl bonds. PMID- 22296100 TI - Pseudogene recoding revealed from proteomic analysis of salmonella serovars. AB - Recoding refers to the reprogramming of mRNA translation by nonstandard read-out rules. In this study, we used stable isotope labeling with amino acids in cell culture (SILAC) technology to investigate the proteome of host-adapted Salmonella serovars, which are characteristic of accumulation of pseudogenes. Interestingly, a few annotated pseudogenes were indeed able to express peptides downstream of the inactivation site, suggesting the occurrence of recoding. Two mechanisms of recoding, namely, programmed frameshifting and codon redefinition, were both found. We believe that the phenomena of recoding are not rare in bacteria. More studies are required for a better understanding of bacterial translation and the implication of pseudogene recoding in Salmonella serovars. PMID- 22296101 TI - Air hunger, unwelcome guests, clogged pipes and idiopathic inflammatory myositis: can we do better? PMID- 22296102 TI - Three-dimensional and molecular analysis of the arterial pole of the developing human heart. AB - Labeling experiments in chicken and mouse embryos have revealed important roles for different cell lineages in the development of the cardiac arterial pole. These data can only fully be exploited when integrated into the continuously changing morphological context and compared with the patterns of gene expression. As yet, studies on the formation of separate ventricular outlets and arterial trunks in the human heart are exclusively based on histologically stained sections. So as to expand these studies, we performed immunohistochemical analyses of serially sectioned human embryos, along with three-dimensional reconstructions. The development of the cardiac arterial pole involves several parallel and independent processes of formation and fusion of outflow tract cushions, remodeling of the aortic sac and closure of an initial aortopulmonary foramen through formation of a transient aortopulmonary septum. Expression patterns of the transcription factors ISL1, SOX9 and AP2alpha show that, in addition to fusion of the SOX9-positive endocardial cushions, intrapericardial protrusion of pharyngeal mesenchyme derived from the neural crest contributes to the separation of the developing ascending aorta from the pulmonary trunk. The non-adjacent walls of the intrapericardial arterial trunks are formed through addition of ISL1-positive cells to the distal outflow tract, while the facing parts of the walls form from the protruding mesenchyme. The morphogenetic steps, along with the gene expression patterns reported in this study, are comparable to those observed in the mouse. They confirm the involvement of mesenchymal tissues derived from endocardium, mesoderm and migrating neural crest cells in the process of initial septation of the distal part of the outflow tract, and its subsequent separation into discrete intrapericardial arterial trunks. PMID- 22296103 TI - PEG nanocages as non-sheddable stabilizers for drug nanocrystals. AB - Many potent drugs are difficult to administer intravenously due to poor aqueous solubility. One validated approach for addressing this issue is to process them into colloidal dispersions known as "nanocrystals" (NCs). However, NCs possess high-energy surfaces that must be stabilized with surfactants to prevent aggregation. In addition, the stabilizer provides a means of anchoring targeting moieties to the NCs for achieving deposition or uptake at specified locations. Nevertheless, a critical challenge is that the surfactant (and consequently the targeting agents) can be shed upon high dilution. This work demonstrates successful cross-linking by click chemistry of stabilizers around paclitaxel NCs to form polymeric "nanocages". Cross-linking does not cause aggregation, as evidenced by transmission electron microscopy, and the nanocages retained the particulate drug through a combination of physical entrapment and physisorption. Size measurements by dynamic light scattering showed that nanocages act as sterically stabilizing barriers to particle-particle interactions and aggregation. The nanocages were shown to be less shed from the NCs than comparable non-cross-linked stabilizers. This contribution provides crucial general tools for preparing poorly sheddable stabilizing coatings to NCs and potentially other classes of nanoparticles for which covalent attachment of the stabilizer to the particle is undesirable (e.g., a drug) or impossible (chemically inert). The presented approach also offers the possibility of more stably attaching targeting moieties to the latter by use of heterotelechelic PEG derivatives, which may favor active targeting and internalization by cells. PMID- 22296104 TI - Enhancing effect of alcoholic solvent on hydrosulfite-hydrogen peroxide chemiluminescence system. AB - In this work, a chemiluminescence (CL) reaction between hydrogen peroxide (H(2)O(2)) and sodium hydrosulfite (NaHSO(3)) was developed. Hydroxyl radical ((*)OH) and sulfite radical ((*)SO(3)(-)) were the main intermediates generated in the NaHSO(3)-H(2)O(2) CL system. Inhibition effects of radical scavengers such as thiourea, chloride ion, nitro blue tetrazolium chloride (NBT), and 5,5 dimethyl-1-pyrroline N-oxide (DMPO) indicated the existence of these two radicals. Singlet oxygen ((1)O(2)) and excited sulfur dioxide (SO(2)*) were emitting species involved in NaHSO(3)-H(2)O(2) CL system. (1)O(2) were confirmed by 1,4-diazobicyclo[2,2,2]octane (DABCO) and sodium azide (NaN(3)), which were specific (1)O(2) scavengers. In addition, electron spin resonance (ESR) spectra clearly show the existence of (1)O(2) and (*)OH. Alcoholic solvent, especially n butanol, enhanced the ultraweak CL emission more than 40 times. The enhancing effect of alcoholic solvent on NaHSO(3)-H(2)O(2) CL system was ascribed to the formation of solvent cage, which can accelerate the reaction rate and protect the emitting species from quenching by water. The CL emission of the NaHSO(3)-n butanol-H(2)O(2) system was measured by cutoff filters. The maximum wavelength was located around 490 nm, which belongs to (1)O(2). The wide peak from 400 to 600 nm is the characteristic peak of SO(2)*. PMID- 22296105 TI - Preparation of oligoalginate plant growth promoter by gamma irradiation of alginate solution containing hydrogen peroxide. AB - Degraded alginate compounds with molecular weights of 7-26, 40-77, or 11-26 kDa were obtained by gamma irradiation, hydrogen peroxide (5% H(2)O(2)) treatment, or a combination treatment involving ionizing radiation and H(2)O(2), respectively. The 14 kDa oligoalginate, prepared by the combined method, promoted the growth of mustard greens and lettuce at an optimal concentration of 75 mg/L. The growth promotion effects of the oligoalginate prepared by gamma irradiation in the presence of H(2)O(2) were statistically equivalent to those of the oligoalginate prepared by gamma irradiation only. The combination of gamma irradiation and H(2)O(2) reduced the required irradiation dosage by a factor of 9 relative to the oligoalginate produced by gamma irradiation only. The combination treatment (gamma irradiation/H(2)O(2)) may be carried out on a large scale at low cost to produce oligoalginate for use as a plant growth promoter in agricultural industries. PMID- 22296106 TI - Effect of gender and stroke rate on joint power characteristics of the upper extremity during simulated rowing. AB - Males typically have greater upper body strength than do females, which is likely to impact on the rowing techniques adopted by each sex. The aim of this study was to quantify energy contributions and compare the joint power production of upper extremity joints between the sexes. Seven males and eight females performed 60 s trials at five different stroke rates. External forces were measured at the handle and stretcher, while kinematics were recorded by motion analysis. Joint moments were derived by inverse dynamic calculations, followed by the calculation of joint powers and gross mechanical energy expenditure. Male rowers expended more total external energy per stroke and made a larger percentage contribution of angular shoulder energy to their total external energy expenditure. As stroke rate increased, the contribution from elbow and angular shoulder energy contributions decreased for both males and females. Female rowers decreased their angular shoulder contribution at a slower rate than did males as stroke rate increased. The overall percentage of work done on the stretcher was higher for male rowers, and this difference further increased at higher stroke rates. The results of this study suggest that specific upper body conditioning may be particularly important for female rowers. PMID- 22296107 TI - Anaerobic benzene degradation under denitrifying conditions: Peptococcaceae as dominant benzene degraders and evidence for a syntrophic process. AB - An anaerobic microbial community was enriched in a chemostat that was operated for more than 8 years with benzene and nitrate as electron acceptor. The coexistence of multiple species in the chemostat and the presence of a biofilm, led to the hypothesis that benzene-degrading species coexist in a syntrophic interaction, and that benzene can be degraded in syntrophy by consortia with various electron acceptors in the same culture. The benzene-degrading microorganisms were identified by DNA-stable isotope probing with [U-(13) C] labelled benzene, and the effect of different electron donors and acceptors on benzene degradation was investigated. The degradation rate constant of benzene with nitrate (0.7 day(-1) ) was higher than reported previously. In the absence of nitrate, the microbial community was able to use sulfate, chlorate or ferric iron as electron acceptor. Bacteria belonging to the Peptococcaceae were identified as dominant benzene consumers, but also those related to Rhodocyclaceae and Burkholderiaceae were found to be associated with the anaerobic benzene degradation process. The benzene degradation activity in the chemostat was associated with microbial growth in biofilms. This, together with the inhibiting effect of hydrogen and the ability to degrade benzene with different electron acceptors, suggests that benzene was degraded via a syntrophic process. PMID- 22296108 TI - Public health services, an essential determinant of health during crisis. Lessons from Cuba, 1989-2000. AB - During the 1990s, Cuba was able to overcome a severe crisis, almost without negative health impacts. This national retrospective study covering the years 1989-2000 analyses the country's strategy through essential social, demographic, health process and health outcome indicators. Gross domestic product (GDP) diminished by 34.76% between 1989 and 1993. In 1994 slow recuperation started. During the crisis, public health expenses increased. The number of family doctors rose from 9.22 to 27.03 per 104 inhabitants between 1989 and 2000. Infant mortality rate and life expectancy exemplify a series of health indicators that continued to improve during the crisis years, whereas low birth weight and tuberculosis incidence are among the few indicators that suffered deterioration. GDP is inversely related to tuberculosis incidence, whereas the average salary is inversely related to low birth weight. Infant mortality rate has a strong negative correlation with the health expenses per inhabitant, the number of maternal homes, the number of family doctors and the proportion of pregnant women receiving care in maternal homes. Life expectancy has a strong positive correlation with health expenses, the number of nursing personnel and the number of medical contacts per inhabitant. The Cuban strategy effectively resolved health risks during the crisis. In times of serious socio-economic constraints, a well conceptualized public health policy can play an important role in maintaining the overall well-being of a population. PMID- 22296109 TI - Optimisation of mesenchymal stromal cells karyotyping analysis: implications for clinical use. AB - PURPOSE: The aim of this study was to optimise the yield of metaphases in mesenchymal stromal cells (MSC) in vitro cultures and to study the karyotype of MSC expanded in good manufacturing practice (GMP) conditions for clinical use. BACKGROUND: MSC are being increasingly used in clinical trials for a number of diseases. Biosafety demonstration in all cases is mandatory. Unfortunately, current standard karyotyping methods fail to obtain enough number of evaluable metaphases. METHODS AND MATERIALS: In the present work, to optimise the yield of metaphases in MSC expanded in vitro, we have tested several conditions by modifying colcemid concentration (we have tested 0.01, 0.05 and 0.1 ug mL(-1) ) and exposure time (during 5, 15 and 24 h). We further applied these optimised conditions to 61 MSC expansions in GMP conditions for clinical use. RESULTS: Our results show that the highest number of metaphases was obtained when MSC were incubated with 0.05 ug mL(-1) of colcemid overnight (15 h), compared to the remaining experimental conditions. In most cases (59/61 cases) enough number of metaphases was obtained. And what is more relevant, only in one case a karyotypic abnormality was found (trisomy of chromosome 10), and cells were subsequently discarded for clinical use. CONCLUSION: We describe here an optimal method to obtain enough number of metaphases for karyotype analysis of in vitro expanded MSCs, what is essential for their clinical use in cell therapy programmes. PMID- 22296110 TI - Combustion performance evaluation of air staging of palm oil blends. AB - The problems of global warming and the unstable price of petroleum oils have led to a race to develop environmentally friendly biofuels, such as palm oil or ethanol derived from corn and sugar cane. Biofuels are a potential replacement for fossil fuel, since they are renewable and environmentally friendly. This paper evaluates the combustion performance and emission characteristics of Refined, Bleached, and Deodorized Palm Oil (RBDPO)/diesel blends B5, B10, B15, B20, and B25 by volume, using an industrial oil burner with and without secondary air. Wall temperature profiles along the combustion chamber axis were measured using a series of thermocouples fitted axially on the combustion chamber wall, and emissions released were measured using a gas analyzer. The results show that RBDPO blend B25 produced the maximum emission reduction of 56.9% of CO, 74.7% of NOx, 68.5% of SO(2), and 77.5% of UHC compared to petroleum diesel, while air staging (secondary air) in most cases reduces the emissions further. However, increasing concentrations of RBDPO in the blends also reduced the energy released from the combustion. The maximum wall temperature reduction was 62.7% for B25 at the exit of the combustion chamber. PMID- 22296111 TI - Comparison of fresh to fixed weights of the vervet monkey (Chlorocebus sabaeus) placenta and its relation to gestational age. AB - BACKGROUND: Focus on the placenta as an agent of fetal development and offspring health outcomes is growing. Primate research facilities or zoos may collect and fix placental tissue for long-term storage, but little is known about the effects of formalin fixation on the non-human primate placenta. METHODS: We obtained 48 vervet monkey placentas from the St. Kitts Biomedical Research Foundation. We investigated via correlation coefficients and ANOVAs the effects of gestational age and original fresh weight on weight change due to fixation. We also used linear regression models to determine whether fixed tissue weight was predictive of fresh weight and gestational age. RESULTS: Although the vervet monkey placenta is described as bidiscoid, 14.6% of the placentas in this sample were fused into a single mass. A decrease in weight was the most common response to formalin fixation, with the greatest degree of loss experienced by the heaviest placentas (ANOVA, F=5.99, P=0.005). Gestational age was unrelated to weight change. Those placentas that increased in weight had the lowest fresh weights. Fixed weights significantly predicted both fresh weight and gestational age (r(2) =0.78, P<0.00001; r(2) =0.76, P<0.00001, respectively). CONCLUSIONS: This paper adds to a sparse literature on the vervet monkey placenta. That fixed placentas are excellent predictors of both fresh weight and gestational age suggests that banked tissue may be a valuable resource for reconstructing aspects of individual life history, although caution must be exercised given the variability of weight change as a function of original placental size. PMID- 22296112 TI - Airway inflammation in asthma, a single measurement is not enough. PMID- 22296113 TI - Mechanistic insights into the 1,3-xylanases: useful enzymes for manipulation of algal biomass. AB - Xylanases capable of degrading the crystalline microfibrils of 1,3-xylan that reinforce the cell walls of some red and siphonous green algae have not been well studied, yet they could prove to be of great utility in algaculture for the production of food and renewable chemical feedstocks. To gain a better mechanistic understanding of these enzymes, a suite of reagents was synthesized and evaluated as substrates and inhibitors of an endo-1,3-xylanase. With these reagents, a retaining mechanism was confirmed for the xylanase, its catalytic nucleophile identified, and the existence of -3 to +2 substrate-binding subsites demonstrated. Protein crystal X-ray diffraction methods provided a high resolution structure of a trapped covalent glycosyl-enzyme intermediate, indicating that the 1,3-xylanases likely utilize the (1)S(3) -> (4)H(3) -> (4)C(1) conformational itinerary to effect catalysis. PMID- 22296114 TI - An approach to aminonaphthoquinone ansamycins using a modified Danishefsky diene. AB - A robust and scalable synthesis of a novel, cyano-substituted Danishefsky-type diene and its use in the Diels-Alder reaction with various dienophiles is reported. The diene allows for the rapid construction of highly substituted aminonaphthoquinones that occur in numerous ansamycin antibiotics. PMID- 22296116 TI - Sequestosome 1/p62: across diseases. AB - Sequestosome 1/p62 is a signal modulator or adaptor protein involved in receptor mediated signal transduction. Sequestosome 1/p62 is gaining attention as it is involved in several diseases including Parkinson disease, Alzheimer disease, liver and breast cancer, Paget's disease of bone, obesity and insulin resistance. In this review, we will focus on the most recent advances on the physiological function of p62 relevant to human diseases. PMID- 22296115 TI - Platelet lysate from whole blood-derived pooled platelet concentrates and apheresis-derived platelet concentrates for the isolation and expansion of human bone marrow mesenchymal stromal cells: production process, content and identification of active components. AB - BACKGROUND AIMS: The clinical use of human mesenchymal stromal cells (MSC) requires ex vivo expansion in media containing supplements such as fetal bovine serum or, alternatively, human platelet lysate (PL). METHODS: Platelet concentrates were frozen, quarantine stored, thawed and sterile filtered to obtain PL. PL content and its effect on fibroblast-colony-forming unit (CFU-F) formation, MSC proliferation and large-scale expansion were studied. RESULTS: PL contained high levels of basic fibroblast growth factor (bFGF), soluble CD40L (sCD40L), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), platelet-derived growth factor AA (PDGF-AA), platelet derived growth factor AB/BB (PDGF-AB/BB), chemokine (C-C) ligand 5 (CCL5; RANTES) transforming growth factor-beta1 (TGF-beta1) and chemokine (C-X-C) ligand 1/2/3 (GRO), with low batch-to-batch variability, and most were stable for up to 14 days. Inhibition of PDGF-BB and bFGF decreased MSC proliferation by about 20% and 50%, respectively. The strongest inhibition (about 75%) was observed with a combination of anti-bFGF + anti-PDGF-BB and anti-bFGF + anti-TGF-beta1 + anti PDGF-BB. Interestingly, various combinations of recombinant PDGF-BB, bFGF and TGF beta1 were not sufficient to promote cell proliferation. PL from whole blood derived pooled platelet concentrates and apheresis platelet concentrates did not differ significantly in their growth-promoting activity on MSC. CONCLUSIONS: PL enhances MSC proliferation and can be regarded as a safe tool for MSC expansion for clinical purposes. ?in particular, PDGF-BB and bFGF are essential components for the growth-promoting effect of PL, but are not sufficient for MSC proliferation. PMID- 22296117 TI - Differential expression of forkhead box M1 and its downstream cyclin-dependent kinase inhibitors p27(kip1) and p21(waf1/cip1) in the diagnosis of pulmonary neuroendocrine tumours. AB - AIMS: Pulmonary neuroendocrine (NE) tumours represent a spectrum of phenotypically distinct entities with different biological behaviours. Difficulties in classifying these tumours are frequently encountered in clinical practice. Forkhead box M1 (FoxM1) is essential for the development of various cancers and is a proliferation-specific transcription factor that regulates transcription of cell cycle genes, including cyclin-dependent kinase inhibitors p27(kip1) and p21(waf1/cip1) . This study was performed to determine the utility of FoxM1, p27(kip1) and p21(waf1/cip1) as immunomarkers for subtyping pulmonary NE tumours. METHODS AND RESULTS: FoxM1, p27(kip1) and p21(waf1/cip1) expression was evaluated by immunohistochemistry in 60 pulmonary NE tumours [19 typical carcinoids (TCs), six atypical carcinoids (ACs), 17 large cell neuroendocrine carcinomas (LCNECs) and 18 small cell lung cancers (SCLCs)]. The frequencies of FoxM1 and p21(waf1/cip1) expression were significantly different between TCs and ACs (each P = 0.009), and those of FoxM1 and p27(kip1) expression were significantly different between LCNECs and SCLCs (P = 0.012 and P = 0.002, respectively). The combined FoxM1((-)) /p21(waf1/cip1(-)) and FoxM1((+)) /p27(kip1(high)) phenotypes had the best diagnostic accuracy for distinguishing TCs from ACs, and SCLCs from LCNECs, respectively. CONCLUSIONS: FoxM1, p27(kip1) and p21(waf1/cip1) showed distinct immunoreactivity according to histological subtype, which may be of value as an ancillary test in the differential diagnosis of pulmonary NE tumours. PMID- 22296118 TI - A toothbrush impalement injury of the floor of mouth in autism child. AB - Penetrating injuries in the oral cavity are common in children. However, penetrating injuries with retained foreign bodies are rare. We report a case of a toothbrush impalement injury of the floor of the mouth in a child with autism. A 5-year-old boy with autism presented with an accidentally impaled toothbrush in the oral cavity. He was taken to the operation room and examined under general anesthesia. The handle of the toothbrush was cut off using rib scissors for mask ventilation, and intra-oral intubation was performed. The toothbrush was located approximately 2.5 cm into the floor of the mouth. The toothbrush was removed uneventfully. Intravenous antibiotic therapy was instituted during hospitalization, and discharge from the hospital occurred 4 days after the operation. PMID- 22296119 TI - Simultaneous presence of human herpesvirus 6 and adenovirus infections in intestinal intussusception of young children. AB - AIM: This prospective study investigated the role of viral infections in the pathogenesis of intussusception, including human herpesvirus 6 (HHV-6), a known lymphotropic virus. METHODS: Fifty-three children with intussusception treated in hospital were enroled, and children of comparable age and gender served as controls. Blood, stool and throat swab specimens, as well as mesenteric lymph nodes and pieces of intestine from patients requiring surgery were tested for various viruses by PCR methods. RESULTS: Altogether, 85% of intussusception cases showed evidence of a recent or ongoing viral infection. Among the 53 intussusception cases, adenovirus was detected in 25 (47%), HHV-6 in 24 (45%), rhinovirus in 12 (23%), cytomegalovirus in 7 (13%), enterovirus in 4 (8%) and rotavirus in 3 (6%) patients. Of the 50 whole blood samples, 44% were positive for HHV-6 and of the 16 resected mesenteric lymph nodes, 50% were positive for HHV-6. Simultaneous presence of HHV-6 and adenovirus infection correlated significantly with intussusception (OR 12.1, 95% CI 2.2 to 66.5). CONCLUSIONS: A statistically significant association was observed between adenovirus and childhood intussusception. HHV-6 was a common finding and occurred concomitantly with other viruses. A simultaneous infection with HHV-6 and adenovirus carried the highest risk for intussusception. PMID- 22296122 TI - Editorial: Regulate the risks. PMID- 22296123 TI - Currents. PMID- 22296125 TI - Looking Back At Love Canal-Part II. PMID- 22296124 TI - Cancer risk management A review of 132 federal regulatory decisions. PMID- 22296126 TI - Regulatory focus: new clean water provisions. PMID- 22296128 TI - ES Books. PMID- 22296127 TI - ES Views: Remote Sensing and Forest Damage. PMID- 22296129 TI - Indirect aluminum toxicity to the green alga Scenedesmus through increased cupric ion activity. PMID- 22296130 TI - Oxidation of H2S in seawater as a function of temperature, pH, and ionic strength. PMID- 22296131 TI - Nitrate-induced photooxidation of trace organic chemicals in water. PMID- 22296132 TI - Fixation, transformation, and mobilization of arsenic in sediments. PMID- 22296133 TI - Experiments on pollutant transport from soil into residential basements by pressure-driven airflow. PMID- 22296134 TI - Volatile organic compound emissions from 46 in-use passenger cars. PMID- 22296135 TI - Determination of polyacrylamides in coal washery effluents by ultrafiltration/size-exclusion chromatography-ultraviolet detection techniques. PMID- 22296136 TI - Wind dispersal of metals from smelter waste tips and their contribution to environmental contamination. PMID- 22296137 TI - Photoproduction of hydrated electrons from natural organic solutes in aquatic environments. PMID- 22296138 TI - Trace element partitioning during the retorting of Julia Creek oil shale. PMID- 22296139 TI - A diffusion monitor to measure exposure to passive smoking. PMID- 22296140 TI - 1-Methylperimidine as a solid monitoring reagent for nitrogen dioxide. PMID- 22296141 TI - Palladium(II)-acetamide complex as a solid monitoring reagent for carbon monoxide. PMID- 22296142 TI - Phenoxazine as a solid monitoring reagent for ozone. PMID- 22296143 TI - Dependence of j[O3-O(1D)] on the choice of extraterrestrial solar irradiance data. PMID- 22296144 TI - Reduction of trihalomethanes in a water-photolysis system. PMID- 22296145 TI - Correction. Reaction products and rates of disappearance of simple bromoalkanes, 1,2-dibromopropane, and 1,2-dibromoethane in water. PMID- 22296146 TI - Correction. Persistence of pesticides in surface soil and relation to sublimation. PMID- 22296147 TI - Chemical constituents of the whole plant of Elsholtzia rugulosa. AB - A new lignan glycoside, 7alpha, 7'beta-bis-(4-hydroxy-3-methoxyphenyl)-7,9':7',9 diepoxylignan-8alphaH,8'alpha-O-beta-d-(2",7'alpha-epoxy)-glucopyranoside, named elshrugulosain (1), has been isolated from the EtOH extract of Elsholtzia rugulosa, together with six known compounds, ( - )-bornyl (E)-3,4,5 trimethoxycinnamate, apigenin, luteolin, apigenin-7-O-beta-d-glucopyranoside, luteolin-7-O-beta-d-glucopyranoside, and luteolin-3'-glucuronate methyl ester. Their structures were characterized by spectroscopic methods and comparison with the data in the literature. On the basis of detailed 1D and 2D NMR spectral analysis, as well as X-ray crystallographic diffraction, the NMR spectroscopic data of ( - )-bornyl (E)-3,4,5-trimethoxycinnamate were revised and assigned completely. PMID- 22296148 TI - New ursane-type triterpene with NO production suppressing activity from Nauclea officinalis. AB - Two new ursane-type triterpenes, named as 3beta, 19alpha, 23, 24-tetrahydroxyurs 12-en-28-oic acid (1) and 2beta, 3beta, 19alpha, 24-tetrahydroxyurs-12-en-28-oic acid (2), together with two known triterpenoids, 3-oxo-urs-12-ene-27, 28-dioic acid (3) and quinovic acid-3-beta-rhamnopyranoside (4), were isolated from the stems (with barks) of Nauclea officinalis. The structures of 1 and 2 were determined by the combined use of single-crystal X-ray diffraction and spectroscopic data analysis. The inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells were examined, and compound 1 was found to inhibit NO production, with the IC(50) value of 4.8 MUM. PMID- 22296149 TI - Two new compounds from Dictamnus dasycarpus. AB - Two new compounds, one new pyrrolidine alkaloid and one new eudesmane-type sesquiterpene derivative, named, respectively, as dictamnaindiol and dictamnadiol, were isolated from the EtOAc soluble fraction of the ethanolic extract from the root barks of Dictamnus dasycarpus. Their structures were elucidated as (3alpha,4beta)-3-(6-ethoxy-6-(4-hydroxyphenyl)methyl)-4-(4 hydroxyphenyl)-1-methyl-pyrrolidin-2-one (1) and (1R, 4S, 7S, 10R)-1,11 dihydroxyl-4,14-epoxy-5(6)-eudesmene (2) on the basis of their spectral and chemical analysis. PMID- 22296150 TI - New guaianolides from Artemisia anomala. AB - Two new guaianolides artemanomalides A and B were isolated from the aerial parts of Artemisia anomala S. Moore. Their structures were characterized as 2-oxo 5alpha, 10alpha-dihydroxy-guaia-3-en-1alpha, 6beta, 7alpha, 11beta H-12, 6-olide (1) and 8alpha-acetoxy-2-oxo-5alpha, 10alpha-dihydroxy-guaia-3, 11(13)-dien 1alpha, 6beta, 7alphaH-12, 6-olide (2) on the basis of extensive spectroscopic analyses. Compounds 1 and 2 showed inhibitory activities against COX-2 enzyme with IC(50) values of 8.8 and 3.6 MUM. PMID- 22296151 TI - Vibralactones G-J from cultures of the basidiomycete Boreostereum vibrans. AB - Four new vibralactone derivatives, named vibralactones G-J (1-4), together with vibralactone (5) have been isolated from cultures of the basidiomycete Boreostereum vibrans. The new structures were elucidated by means of spectroscopic methods. PMID- 22296152 TI - Two new flavonoid glycosides from Semen Ziziphi Spinosae. AB - Two novel flavonoid glycosides, 6"'-dihydrophaseoylspinosin (1) and 6",6"' diferuloylspinosin (2), were isolated from the MeOH extract of Semen Ziziphi Spinosae, together with six known flavonoids, isovitexin-2"-O-beta-(6-O-E feruloyl)glucopyranoside (3), spinosin (4), isospinosin (5), 6"'-feruloylspinosin (6), swertisin (7), and isovitexin-2"-O-beta-d-glucopyranoside (8). The structures of 1 and 2 were elucidated by spectroscopic methods including UV, IR, ESI-TOF-MS, 1D NMR, and 2D NMR experiments. PMID- 22296153 TI - Lignans from Kadsura angustifolia and Kadsura coccinea. AB - Further phytochemical investigation of Kadsura angustifolia and Kadsura coccinea led to the isolation of six lignans and one flavonoid, including two new lignans named kadangustin L(1) and kadcoccilignan (2). The structures and stereochemistry of 1 and 2 were elucidated by analysis of spectroscopic data. PMID- 22296154 TI - Two methyl-migrated 16,17-seco-dammarane triterpenoid saponins from the seeds of Hovenia acerba. AB - Two new methyl-migrated 16,17-seco-dammarane triterpenoid saponins, named acerboside A (1) and acerboside B (2), were isolated from the seeds of Hovenia acerba. Their structures were elucidated on the basis of spectroscopic analysis and hydrolysis. PMID- 22296155 TI - Two new xanthones from Swertia angustifolia. AB - Two new xanthones, angustins A and B (1 and 2), were isolated from the aerial parts of Swertia angustifolia together with six known compounds (3-8). The structures of these two xanthones were elucidated by extensive analysis of the spectroscopic data. In addition, compounds 3 and 6-8 were isolated from this plant for the first time. PMID- 22296156 TI - Two new lignans from Celastrus flagellaris Rupr. AB - Two new lignans (R-biar)-12-angeloyloxy-6,7,8,9-tetrahydro-1,2,3,13,14 pentamethoxy-7,8-dimethyl-7-dibenzo[a,c]cyclooctenol (1) and (R-biar)-12 benzoyloxy-6,7,8,9-tetrahydro-1,2,3,13,14-pentamethoxy-7,8-dimethyl-7 dibenzo[a,c]cyclooctenol (2) were isolated from the stems of Celastrus flagellaris Rupr. Their structures were elucidated on the basis of spectroscopic methods including HR-EI-MS, 1D and 2D NMR, HMQC, NOESY, and CD. PMID- 22296157 TI - Smilasides M and N, two new phenylpropanoid glycosides from Smilax riparia. AB - Two new phenylpropanoid glycosides, smilasides M and N, together with the known compound 2',6'-diacetyl-3,6-diferuloylsucrose, were isolated and characterized from the roots and rhizomes of Smilax riparia A. DC. The structures of the new compounds were elucidated as 2',6'-diacetyl-3-Z-feruloyl-6-feruloylsucrose (1) and 2',6'-diacetyl-3-feruloyl-6-Z-feruloylsucrose (2) on the basis of extensive analysis of HR-ESI-MS, UV, IR, and 1D and 2D NMR spectroscopic data. PMID- 22296158 TI - Two new rhamnopyranosides of neolignans from Sanguisorba officinalis. AB - Two new rhamnopyranosides of neolignans, (7S,8R)-4,9,5',9'-tetrahydroxy-3,3' dimethoxy-8-O-4'-neolignan-7-O-alpha-l-rhamnopyranoside (1) and (7S,8R)-4,9,9' trihydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan-7-O-alpha-l-rhamnopyranoside (2), together with a known compound (7S,8R)-4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8-O 4'-neolignan (3), were isolated from the 80% EtOH extract of the roots of Sanguisorba officinalis. Their structures were characterized by spectroscopic analysis including 1D NMR, 2D NMR, and HR-ESI-MS, and chemical method. PMID- 22296159 TI - Determination of novel nitrogen-containing metabolite after oral administration of swertiamarin to rats. AB - In a series of studies on the metabolism of iridoid compounds, we investigated the metabolic fate of swertiamarin (1) in Wistar rats. Liquid chromatography/ion trap mass spectrometry detected new nitrogen-containing metabolite gentiandiol (3) in rat plasma. The structure of the metabolite was unequivocally identified by comparing the retention time as well as the mass spectrum with those of authentic compound, which was synthesized from swertiamarin (1). The transformation of swertiamarin to nitrogen-containing metabolite gentiandiol (3) in vivo was verified for the first time. Understanding of this unique metabolic pathway may shed light on clinical efficacy of swertiamarin (1) and will also assist in studies for the metabolism of other natural iridoids in vivo. PMID- 22296160 TI - A new inositol derivative from Prenanthes macrophylla. AB - A new chiro-inositol ester, 4-hydroxyphenylacetyl-3-d-chiro-inositol ester (1), was isolated from the whole plants of Prenanthes macrophylla Franch., along with 10 known compounds, 4-hydroxyphenylacetic acid (2), trans-ethyl caffeate (3), cis ethyl caffeate (4), protocatechualdehyde (5), luteolin (6), luteolin-7-O-beta-d glucoside (7), 15-hydroxy-2-oxo-guai-3-en 1alpha,5alpha,6beta,7alpha,10alpha,11betaH-12,6-olide (8), 15-glucopyranosyloxy-2 oxo-guaia-3,11(13)-dien-1alpha,5alpha,6beta,7alpha,10alphaH-12,6-olide (9), ursolic acid (10), and oleanolic acid (11). Their structures were elucidated on the basis of spectroscopic analyses including HR-ESI-MS, ESI-MS, (1)H and (13)C NMR, HSQC, HMBC, and ROESY, and chemical evidences. PMID- 22296161 TI - Ethnic uses, pharmacological and phytochemical profile of genus Grewia. AB - A number of species of genus Grewia have been used as medicinal agents to treat several diseases. This review based on 45 literary sources discusses the current knowledge of traditional uses, chemistry, biological effects, and toxicity of different species of this genus. Triterpenoids, steroids, glycosides, flavones, lignans, phenolics, alkaloids, lactones, anthocyanins, flavones, and organic acids have been isolated from various species of this genus. The extracts and preparations from the various plants, which are expectantly safe, exhibited various biological effects, e.g. anti-oxidant, anti-bacterial, hepatoprotective, anti-inflammatory, anti-emetic, anti-malarial, analgesic, and anti-pyretic activities. PMID- 22296162 TI - Analysis of tubulin alpha-1A/1B C-terminal tail post-translational poly glutamylation reveals novel modification sites. AB - Tubulin-alpha(1A/1B) C-terminal tail (CTT) has seven glutamic acid residues among the last 11 amino acids of its sequence that are potential sites for glutamylation. Cleavage of C-terminal tyrosine resulting in the detyrosinated form of tubulin-alpha(1A/1B) is another major modification. These modifications among others bring about highly heterogeneous tubulin samples in brain cells and microtubules, play a major role in directing intracellular trafficking, microtubule dynamics, and mitotic events, and can vary depending on the cell and disease state, such as cancer and neurodegenerative disorders. Identified previously using primary mass spectrometry (MS) ions and partial Edman sequencing, tubulin-alpha(1A/1B) glutamylation was found exclusively on the E(445) residue. We here describe the analysis of tubulin-alpha(1A/1B) glutamylation and detyrosination after 2-DE separation, trypsin and proteinase K in-gel digestion, and nanoUPLC-ESI-QqTOF-MS/MS of mouse brain and bovine microtubules. Tyrosinated, detyrosinated, and Delta2-tubulin-alpha(1A/1B) CTTs were identified on the basis of a comparison of fragmentation patterns and retention times between endogenous and synthetic peptides. Stringent acceptance criteria were adapted for the identification of novel glutamylation sites. In addition to the previously identified site at E(445), glutamylation on mouse and bovine tubulin-alpha(1A/1B) CTTs was identified on E(441) and E(443) with MASCOT Expect values below 0.01. O-Methylation of glutamates was also observed. PMID- 22296164 TI - Human handedness in interactive situations: Negative perceptual frequency effects can be reversed! AB - Left-handed performers seem to enjoy an advantage in interactive sports. Researchers suggest this is predominantly due to the relative scarcity of left handers compared with right-handers. Such negative frequency-dependent advantages are likely to appear in inefficient game-play behaviour against left-handed opponents such as reduced ability to correctly anticipate left-handers' action intentions. We used a pre-post retention design to test whether such negative frequency-dependent perceptual effects can be reversed via effective training. In a video-based test, 30 handball novices anticipated the shot outcome of temporally occluded handball penalties thrown by right- and left-handed players. Between the pre- and post-tests, participants underwent a perceptual training programme to improve prediction accuracy, followed by an unfilled retention test one week later. Participants were divided into two hand-specific training groups (i.e. only right- or left-handed shots were presented during training) and a mixed group (i.e. both right- and left-handed shots were presented). Our results support the negative frequency-dependent advantage hypothesis, as hand-specific perceptual training led to side-specific improvement of anticipation skills. Similarly, findings provide experimental evidence to support the contention that negatively frequency-dependent selection mechanisms contributed to the maintenance of the handedness polymorphism. PMID- 22296163 TI - The use of design-based stereology to evaluate volumes and numbers in the liver: a review with practical guidelines. AB - Stereology offers a number of tools for the analysis of sections in microscopy (which usually provide only two-dimensional information) for the purpose of estimating geometric quantities, such as volume, surface area, length or number of particles (cells or other structures). The use of these tools enables recovery of the three-dimensional information that is inherent in biological tissues. This review uses the liver as a paradigm for summarizing the most commonly used state of-the-art methods for quantitation in design-based stereology. Because it is often relevant to distinguish hyperplasia and hypertrophy in liver responses, we also focus on potential pitfalls in the sampling and processing of liver specimens for stereological purposes, and assess the existing methods for volume and number estimation. With respect to volume, we considered whole liver volume (V), volume density (V(V)) and so-called local volumes, including the number weighted volume (V(N)) and the volume-weighted volume (V(V)). For number, we considered the total number (N) and the numerical density (N(V)). If correctly applied, current stereological methods guarantee that no bias is introduced in the estimates, which will be therefore accurate; additionally, methods can be tuned for obtaining precise quantitative estimates that can reveal subtle changes in the volume or number of selected hepatic cells. These methods have already detailed the effects of some substances and specific diets on the liver, and should be routinely included in the toolbox of liver research. PMID- 22296165 TI - Intersystem crossing involving strongly spin exchange-coupled radical ion pairs in donor-bridge-acceptor molecules. AB - Intersystem crossing involving photogenerated strongly spin exchange-coupled radical ion pairs in a series of donor-bridge-acceptor molecules was examined. These molecules have a 3,5-dimethyl-4-(9-anthracenyl)-julolidine (DMJ-An) donor either connected directly or connected by a phenyl bridge (Ph), to pyromellitimide (PI), 1 and 2, respectively, or naphthalene-1,8:4,5 bis(dicarboximide) (NI) acceptors, 3 and 4, respectively. Femtosecond transient optical absorption spectroscopy shows that photodriven charge separation produces DMJ(+*)-PI(-*) or DMJ(+*)-NI(-*) quantitatively in 1-4 (tau(CS) <= 10 ps), and that charge recombination occurs with tau(CR) = 268 and 158 ps for 1 and 3, respectively, and with tau(CR) = 2.6 and 10 ns for 2 and 4, respectively. Magnetic field effects (MFEs) on the neutral triplet state yield produced by charge recombination were used to measure the exchange coupling (2J) between DMJ(+*) and PI(-*) or NI(-*), giving 2J > 600 mT for 1-3 and 2J = 170 mT for 4. Time-resolved electron paramagnetic resonance (TREPR) spectroscopy revealed that the formation of (3)*An upon charge recombination occurs by spin-orbit charge transfer intersystem crossing (SOCT-ISC) and/or radical-pair intersystem crossing (RP-ISC) mechanisms with the magnitude of 2J determining which triplet formation mechanism dominates. SOCT-ISC is the exclusive triplet formation mechanism in 1 3, whereas both RP-ISC and SOCT-ISC are active for 4. The triplet sublevels populated by SOCT-ISC in 1-4 depend on the donor-acceptor geometry in the charge separated state. This is consistent with the fact that the SOCT-ISC mechanism requires the relevant donor and acceptor orbitals to be nearly perpendicular, so that electron transfer results in a large orbital angular momentum change that must be compensated by a fast spin flip to conserve overall system angular momentum. PMID- 22296166 TI - Room for manoeuvre when prescribing statins to dyslipidaemic patients on antiretroviral therapy. PMID- 22296167 TI - Evaluation of the diagnostic accuracy of the Haemoglobin Colour Scale to detect anaemia in young children attending primary healthcare clinics in Zanzibar. AB - OBJECTIVES: This study evaluates the diagnostic accuracy of Haemoglobin Colour Scale (HCS), compared with clinical diagnosis, to detect anaemia and severe anaemia in preschool-age children attending primary healthcare clinics in rural Zanzibar. METHODS: In all participants, haemoglobin (Hb) concentration was independently estimated by clinical examination for palmar pallor, HCS and HemoCueTM. HemoCue was considered the reference method. Data collection was integrated into the usual health services and performed by local healthcare workers (HCWs). Sensitivity, specificity, positive and negative predictive values were calculated for HCS and clinical examination for palmar pallor. The limits of agreement between HCS and HemoCue, and inter-observer variability for HCS, were also defined. RESULTS: A total of 799 children age 2-59 months were recruited to the study. The prevalence of anaemia (Hb<11 g/dl) and severe anaemia (<5 g/dl) were 71% and 0.8% respectively. The sensitivity of HCS to detect anaemia was 33% [95% confidence interval (CI) 29-36] and specificity was 87% (83-91). The sensitivity of HCS to detect severe anaemia was 14% (95% CI 0-58) and specificity was 100% (99-100). The sensitivity of palmar pallor to detect anaemia was low, but superior to HCS (58% vs. 33%, P<0.001); specificity was inferior to HCS (55% vs. 87%, P<0.001). There was no evidence of a difference in either sensitivity (P>0.1) or specificity (P>0.1) between HCS and palmar pallor to detect severe anaemia. CONCLUSIONS: Haemoglobin Colour Scale does not improve the capacity of HCWs to diagnose anaemia in this population. Accuracy is limited by considerable variability in the performances of test operators. However, optimizing the training protocol for those using the test may improve performance. PMID- 22296168 TI - Beer a no-go: learning to stop responding to alcohol cues reduces alcohol intake via reduced affective associations rather than increased response inhibition. AB - AIMS: Previous research has shown that consistently not responding to alcohol related stimuli in a go/no-go training procedure reduces drinking behaviour. This study aimed to examine further the mechanisms underlying this go/no-go training effect. DESIGN, SETTING AND PARTICIPANTS: Fifty-seven heavy drinkers were assigned randomly to two training conditions: in the beer/no-go condition, alcohol-related stimuli were always paired with a stopping response, while in the beer/go condition participants always responded to alcohol-related stimuli. Participants were tested individually in a laboratory at Maastricht University. MEASUREMENTS: Weekly alcohol intake, implicit attitudes towards beer, approach avoidance action tendencies towards beer and response inhibition were measured before and after the training. FINDINGS: Results showed a significant reduction in both implicit attitudes (P = 0.03) and alcohol intake (P = 0.02) in the beer/no-go condition, but not in the beer/go condition. There were no significant training effects on action tendencies or response inhibition. CONCLUSIONS: Repeatedly stopping pre-potent responses towards alcohol-related stimuli reduces excessive alcohol use via a devaluation of alcohol-related stimuli rather than via increased inhibitory control over alcohol-related responses. PMID- 22296169 TI - Health benefits of almonds beyond cholesterol reduction. AB - Almonds are rich in monounsaturated fat, fiber, alpha-tocopherol, minerals such as magnesium and copper, and phytonutrients, albeit being energy-dense. The favorable fat composition and fiber contribute to the hypocholesterolemic benefit of almond consumption. By virtue of their unique nutrient composition, almonds are likely to benefit other modifiable cardiovascular and diabetes risks, such as body weight, glucose homeostasis, inflammation, and oxidative stress. This paper briefly reviews the nutrient composition and hypocholesterolemic benefits; the effects of almond consumption on body weight, glucose regulation, oxidative stress, and inflammation, based on the data of clinical trials, will then be discussed. Although more studies are definitely warranted, the emerging evidence supports that almond consumption beneficially influences chronic degenerative disease risk beyond cholesterol reduction, particularly in populations with metabolic syndrome and type 2 diabetes mellitus. PMID- 22296170 TI - Human therapeutic plasma levels of the selective serotonin reuptake inhibitor (SSRI) sertraline decrease serotonin reuptake transporter binding and shelter seeking behavior in adult male fathead minnows. AB - Selective serotonin reuptake inhibitors (SSRIs) represent a class of pharmaceuticals previously reported in aquatic ecosystems. SSRIs are designed to treat depression and other disorders in humans, but are recognized to elicit a variety of effects on aquatic organisms, ranging from neuroendocrine disruption to behavioral perturbations. However, an understanding of the relationships among mechanistic responses associated with SSRI targets and ecologically important behavioral responses of fish remains elusive. Herein, linking Adverse Outcomes Pathways (AOP) models with internal dosimetry represent potential approaches for developing an understanding of pharmaceutical risks to aquatic life. We selected sertraline as a model SSRI for a 28-d study with adult male fathead minnows. Binding activity of the serotonin reuptake transporter (SERT), previously demonstrated in mammals and fish models to respond to sertraline exposure, was selected as an endpoint associated with therapeutic activity. Shelter-seeking behavior was monitored using digital tracking software to diagnose behavioral abnormalities. Fish plasma levels of sertraline exceeding human therapeutic doses were accurately modeled from external exposure concentrations when pH influences on ionization and log D were considered. We observed statistically significant decreases in binding at the therapeutic target (SERT) and shelter-seeking behavior when fish plasma levels exceeded human therapeutic thresholds. Such observations highlights the strengths of coupling physiologically based pharmacokinetic modeling and AOP approaches and suggest that internal dosimetry should be monitored to advance an understanding of the ecological consequences of SSRI exposure to aquatic vertebrates. PMID- 22296171 TI - Multi-locus HLA class I and II allele and haplotype associations with follicular lymphoma. AB - Follicular lymphoma (FL) is an indolent, sometimes, fatal disease characterized by recurrence at progressively shorter intervals and is frequently refractive to therapy. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region on chromosome 6p21.32-33 that are statistically significantly associated with FL risk. Low to medium resolution typing of single or multiple HLA genes has provided an incomplete picture of the total genetic risk imparted by this highly variable region. To gain further insight into the role of HLA alleles in lymphomagenesis and to investigate the independence of validated SNPs and HLA alleles with FL risk, high-resolution HLA typing was conducted using next-generation sequencing in 222 non-Hispanic White FL cases and 220 matched controls from a larger San Francisco Bay Area population-based case-control study of lymphoma. A novel protective association was found between the DPB1*03:01 allele and FL risk [odds ratio (OR) = 0.39, 95% confidence interval (CI) = 0.21-0.68]. Extended haplotypes DRB1*01:01-DQA1*01:01-DQB1*05:01 (OR = 2.01, 95% CI = 1.22-3.38) and DRB1*15 DQA1*01-DQB1*06 (OR = 0.55, 95% CI = 0.36-0.82) also influenced FL risk. Moreover, DRB1*15-DQA1*01-DQB1*06 was highly correlated with an established FL risk locus, rs2647012. These results provide further insight into the critical roles of HLA alleles and SNPs in FL pathogenesis that involve multi-locus effects across the HLA region. PMID- 22296172 TI - Mukaiyama-Michael reactions with acrolein and methacrolein: a catalytic enantioselective synthesis of the C17-C28 fragment of pectenotoxins. AB - Enantioselective iminium-catalyzed reactions with acrolein and methacrolein are rare. A catalytic enantioselective Mukaiyama-Michael reaction that readily accepts acrolein or methacrolein as substrates, affording the products in good yields and 91-97% ee, is presented. As an application of the methodology, an enantioselective route to the key C17-C28 segment of the pectenotoxin using the Mukaiyama-Michael reaction as the key step is described. PMID- 22296173 TI - Recycling of carbon and silicon wastes: room temperature formylation of N-H bonds using carbon dioxide and polymethylhydrosiloxane. AB - A highly active organocatalytic system based on N-heterocyclic carbenes has been designed for the formylation of N-H bonds in a large variety of nitrogen molecules and heterocycles, using two chemical wastes: CO(2) and polymethylhydrosiloxane (PMHS). PMID- 22296174 TI - Photostabilization of ascorbic acid with citric acid, tartaric acid and boric acid in cream formulations. AB - This study involves the evaluation of the effect of certain stabilizers, that is, citric acid (CT), tartaric acid (TA) and boric acid (BA) on the degradation of ascorbic acid (AH(2) ) in oil-in-water cream formulations exposed to the UV light and stored in the dark. The apparent first-order rate constants (0.34-0.95 * 10( 3) min(-1) in light, 0.38-1.24 * 10(-2) day(-1) in dark) for the degradation reactions in the presence of the stabilizers have been determined. These rate constants have been used to derive the second-order rate constants (0.26-1.45 * 10(-2) M(-1) min(-1) in light, 3.75-8.50 * 10(-3) M(-1) day(-1) in dark) for the interaction of AH(2) and the individual stabilizers. These stabilizers are effective in causing the inhibition of the rate of degradation of AH(2) both in the light and in the dark. The inhibitory effect of the stabilizers is in the order of CT > TA > BA. The rate of degradation of AH(2) in the presence of these stabilizers in the light is about 120 times higher than that in the dark. This could be explained on the basis of the deactivation of AH(2) -excited triplet state by CT and TA and by the inhibition of AH(2) degradation through complex formation with BA. AH(2) leads to the formation of dehydroascorbic acid (A) by chemical and photooxidation in cream formulations. PMID- 22296175 TI - Tissue engineering for pulmonary diseases: insights from the laboratory. AB - Recent advances in stem cell research and tissue engineering have opened new paradigms for future therapies towards many intractable diseases. Many tissue engineering approaches are also applied in the pulmonary research field. Several materials have been utilized as scaffolds to support lung tissue engineering to recapitulate the three-dimensional (3D) structure of the lung. Natural products and synthetic polymers are the two major components of the scaffold materials. Decellularization of allogeneic or xenogenic donor lungs is also utilized to obtain biological 3D matrix scaffolds. Decellularized lungs are recellularized with stem or progenitor cells. Cell sources are the key components for tissue engineering. The best cell source for tissue engineering is autologous cells obtained from patients because it does not induce an immunological response after transplantation. However, the stem/progenitor population in adult organs is generally small, and their capacity for proliferation or differentiation is limited. Knowledge about the endogenous stem/progenitor population in lung tissue has been expanded recently. Although the lung is the most challenging organ for tissue engineering because of its complex 3D structure and more than 40 different cell types, several breakthroughs in respiratory research have been made. These results give us a greater understanding of the possibilities and the limitations of tissue engineering for pulmonary diseases. PMID- 22296176 TI - Expression of vascular Notch ligands Delta-like 4 and Jagged-1 in glioblastoma. AB - AIMS: The coordinated expression of the Notch ligands Delta-like 4 (Dll4) and Jagged (Jag)1 is believed to define appropriate endothelial sensitivity to vascular endothelial growth factor (VEGF). Preclinical data suggest that Dll4 Notch signalling may confer resistance to anti-VEGF therapy with bevacizumab, and Jag1 may antagonize Dll4-Notch. The aims of this study were to characterize the expression of Dll4 and Jag1 in primary glioblastomas. METHODS AND RESULTS: Immunohistochemistry was performed on 40 glioblastomas and normal brain using validated antibodies against Dll4 and Jag1. In-situ hybridization for Dll4 was performed on serial sections and compared with protein expression. Dll4 expression was localized to the cytoplasm and membrane of endothelial cells in all glioblastomas; it was weak or absent in normal brain. Jag1 expression was observed in the cytoplasm and membrane of glomeruloid and non-glomeruloid endothelial cells from 76% and 67% of glioblastomas, respectively. However, endothelial Jag1 expression was less intense and less prevalent than Dll4. There was no association between Dll4 and Jag1 expression. CONCLUSIONS: In summary, Dll4 and Jag1 are expressed in glioblastoma vasculature. These data may define subsets of glioblastoma that might be sensitive (Dll4(+) /Jag1(+) ) or resistant (Dll4(+) /Jag1(-) ) to bevacizumab. Our data also suggest that anti-Dll4 therapy should be evaluated experimentally in glioblastoma. PMID- 22296178 TI - Application of an in vitro DDASS to evaluate oral absorption of two chemicals simultaneously: establishment of a level A in vitro-in vivo correlation. AB - The aim of this study was to evaluate the oral absorption of two chemicals simultaneously using a drug dissolution/absorption simulating system (DDASS), and to establish a correlation between DDASS and in vivo absorption to clarify the prediction of this in vitro model. Ferulic acid (FA) and tetrahydropalmatine (THP), the components of Angelicae Sinensis Radix and Corydalis Yanhusuo Rhizoma, respectively, were chosen as model compounds. Three groups including FA, THP, and FA and THP together (FA + THP) were studied in DDASS. The corresponding in vivo pharmacokinetics study was performed in rats. Then the correlation was analysed between DDASS permeation in vitro and rat absorption data in vivo. A strong level A correlation (r > 0.84) was obtained after a correlation coefficient test (p < 0.05 or 0.01). Moreover, when FA and THP were used together in DDASS, the cumulative permeation of FA increased by 38.5%, while THP permeation decreased by 25.8%. In rats, the area under the concentration-time curve from time to infinity for FA increased 2.6-fold, while THP decreased 19.6%. The changes in rat intestinal permeation modeled by the DDASS were consistent with the absorption changes in rats. We conclude that DDASS is a valid in vitro model to evaluate oral absorption of two drug components simultaneously and reflect the in vivo characteristics of drug absorption accurately. PMID- 22296180 TI - The effect of various concentrations of iodine potassium iodide on the antimicrobial properties of mineral trioxide aggregate--a pilot study. AB - BACKGROUND: Mineral trioxide aggregate (MTA) is a multi-purpose dental material with various uses in dentistry. Iodine potassium iodide (IKI) is the most commonly used iodine compound in endodontics. We aimed to assess the antimicrobial activity of tooth-colored ProRoot MTA combined with IKI. MATERIALS AND METHODS: The antimicrobial activity of IKI was assessed at three concentrations (1%, 2%, and 4%) as the mixing agents combined with MTA against Enterococcus faecalis, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. For each microorganism, three plates were inoculated with 100 MUl of a microbial suspension (McFarland 0.5). Four wells were prepared in each plate. MTA (70 mg) was mixed with any of the three concentrations of IKI (25 MUl) or sterile distilled water (25 MUl) and placed in each well. The plates were incubated for 24 h at 37 degrees C. Zones of inhibition (ZOI) were measured in millimeters by a blinded observer. Data were analyzed using analysis of variance and the Dunnett t-test. RESULTS: All MTA mixtures with water or IKI solutions showed inhibitory zones. The mean ZOI of each MTA/IKI mixture was not significantly different from MTA/water mixture (P > 0.05). MTA/1% IKI had smaller ZOI than MTA/water against E. coli, E. faecalis, and C. albicans. MTA/2% IKI showed larger ZOI only against P. aeruginosa. MTA/4% IKI showed larger ZOI against P. aeruginosa and E. coli (P < 0.05). CONCLUSIONS: Substitution of IKI solutions (1%, 2%, and 4%) for water did not significantly increase the antimicrobial activity of MTA. PMID- 22296179 TI - Islet preconditioning via multimodal microfluidic modulation of intermittent hypoxia. AB - Simultaneous stimulation of ex vivo pancreatic islets with dynamic oxygen and glucose is a critical technique for studying how hypoxia alters glucose stimulated response, especially in transplant environments. Standard techniques using a hypoxic chamber cannot provide both oxygen and glucose modulations, while monitoring stimulus-secretion coupling factors in real-time. Using novel microfluidic device with integrated glucose and oxygen modulations, we quantified hypoxic impairment of islet response by calcium influx, mitochondrial potentials, and insulin secretion. Glucose-induced calcium response magnitude and phase were suppressed by hypoxia, while mitochondrial hyperpolarization and insulin secretion decreased in coordination. More importantly, hypoxic response was improved by preconditioning islets to intermittent hypoxia (IH, 1 min/1 min 5-21% cycling for 1 h), translating to improved insulin secretion. Moreover, blocking mitochondrial K(ATP) channels removed preconditioning benefits of IH, similar to mechanisms in preconditioned cardiomyocytes. Additionally, the multimodal device can be applied to a variety of dynamic oxygen-metabolic studies in other ex vivo tissues. PMID- 22296181 TI - General self-efficacy influences affective task reactions during a work simulation: the temporal effects of changes in workload at different levels of control. AB - This study investigated the effects of workload, control, and general self efficacy on affective task reactions (i.e., demands-ability fit, active coping, and anxiety) during a work simulation. The main goals were (1) to determine the extent general self-efficacy moderates the effects of demand and control on affective task reactions and (2) to determine if this varies as a function of changes in workload. Participants (N=141) completed an inbox activity under conditions of low or high control and within low and high workload conditions. The order of trials varied so that workload increased or decreased. Results revealed individuals with high general self-efficacy reported better demands abilities fit and active coping as well as less anxiety. Three interactive effects were found. First, it was found that high control increased demands abilities fit from trial 1 to trial 2, but only when workload decreased. Second, it was found that low efficacious individuals active coping increased in trial 2, but only under high control. Third, it was found that high control helped high efficacious individuals manage anxiety when workload decreased. However, for individuals with low general self-efficacy, neither high nor low control alleviated anxiety (i.e., whether workload increased or decreased over time). PMID- 22296182 TI - Are T-cell dysfunctions the other side of the moon in the pathogenesis of myelodysplastic syndromes? AB - Even though the pathogenesis of myelodysplastic syndromes (MDS) is dominated by an inefficient maturation of haematopoietic precursors, also immune mechanisms seem to play a crucial functional role. In this review, we will first describe the clinical and laboratory autoimmune manifestations often detectable in MDS patients. We will then focus on studies addressing the mechanisms of T-cell activation and their implications in the disease history. The potential impact of specific cell subsets, such as regulatory T-cells, Th17 cells and natural killer cells, will be also described. We will finally focus on potential therapeutic approaches based on immunomodulation, ranging from more classical immunosuppressive drugs to vaccination and transplantation strategies. PMID- 22296183 TI - Gender-based differences in the shape of the human corpus callosum are associated with allometric variations. AB - The corpus callosum displays considerable morphological variability between individuals. Although some characteristics are thought to differ between male and female brains, there is no agreement regarding the source of this variation. Biomedical imaging and geometric morphometrics have provided tools to investigate shape and size variation in terms of integration and correlation. Here we analyze variations at the midsagittal outline of the corpus callosum in a sample of 102 young adults in order to describe and quantify the pattern of covariation associated with its morphology. Our results suggest that the shape of the corpus callosum is characterized by low levels of morphological integration, which explains the large variability. In larger brains, a minor allometric component involves a relative reduction of the splenium. Small differences between males and?females are associated with this allometric pattern, induced primarily by size variation rather than gender-specific characteristics. PMID- 22296184 TI - Water oxidation electrocatalyzed by an efficient Mn3O4/CoSe2 nanocomposite. AB - The design of efficient, cheap, and abundant oxygen evolution reaction (OER) catalysts is crucial to the development of sustainable energy sources for powering fuel cells. We describe here a novel Mn(3)O(4)/CoSe(2) hybrid which could be a promising candidate for such electrocatalysts. Possibly due to the synergetic chemical coupling effects between Mn(3)O(4) and CoSe(2), the constructed hybrid displayed superior OER catalytic performance relative to its parent CoSe(2)/DETA nanobelts. Notably, such earth-abundant cobalt (Co)-based catalyst afforded a current density of 10 mA cm(-2) at a small overpotential of ~0.45 V and a small Tafel slope down to 49 mV/decade, comparable to the best performance of the well-investigated cobalt oxides. Moreover, this Mn(3)O(4)/CoSe(2) hybrid shows good stability in 0.1 M KOH electrolyte, which is highly required to a promising OER electrocatalyst. PMID- 22296185 TI - Sequence and in vitro function of chicken, ring-necked pheasant, and Japanese quail AHR1 predict in vivo sensitivity to dioxins. AB - There are large differences in sensitivity to the toxic and biochemical effects of dioxins and dioxin-like compounds (DLCs) among vertebrates. Previously, we demonstrated that the difference in sensitivity between domestic chicken (Gallus gallus domesticus) and common tern (Sterna hirundo) to aryl hydrocarbon receptor 1 (AHR1)-dependent changes in gene expression following exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is based upon the identities of the amino acids at two sites within the ligand binding domain of AHR1 (chicken--highly sensitive; Ile324_Ser380 vs common tern--250-fold less sensitive than chicken; Val325_Ala381). Here, we tested the hypotheses that (i) the sensitivity of other avian species to TCDD, 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), and 2,3,7,8 tetrachlorodibenzofuran (TCDF) is also determined by the amino acids at sites that are equivalent to sites 324 and 380 in chicken, and (ii) Ile324_Ala380 and Val324_Ser380 genotypes confer intermediate sensitivity to DLCs in birds. We compared ligand-induced transactivation function of full-length AHR1s from chicken, common tern, ring-necked pheasant (Phasianus colchicus; Ile324_Ala380) and Japanese quail (Coturnix japonica; Val324_Ala380), and three Japanese quail AHR1 mutants. The results support our hypothesis that avian species can be grouped into three general classes of sensitivity to DLCs. Both AHR1 genotype and in vitro transactivation assays predict in vivo sensitivity. Contrary to the assumption that TCDD is the most potent DLC, PeCDF was more potent than TCDD at activating Japanese quail (13- to 26-fold) and common tern (23- to 30-fold) AHR1. Our results support and expand previous in vitro and in vivo work that demonstrated ligand-dependent species differences in AHR1 affinity. The findings and methods will be of use for DLC risk assessments. PMID- 22296186 TI - Control of solid tumor growth in mice using EGF receptor-targeted RNA replicase based plasmid DNA. AB - AIM: Previously, it was shown that treatment of tumor-bearing mice with an RNA replicase-based plasmid that produces dsRNA when transfected into tumor cells significantly inhibited the tumor growth. In the present study, the feasibility of further improving the anti-tumor activity of the RNA replicase-based plasmid by targeting it into tumors cells was evaluated. MATERIAL & METHODS: An EGF conjugated, polyethylene glycosylated cationic liposome was developed to deliver the RNA replicase-based plasmid, pSIN-beta, into EGF receptor-overexpressing human breast cancer cells (MDA-MB-468) in vitro and in vivo. RESULTS: Delivery of pSIN-beta using the EGF receptor-targeted liposome more effectively controlled the growth of MDA-MB-468 tumors (and human epidermoid carcinoma A431 tumors) in mice than using untargeted liposome. The pSIN-beta carried by the EGF receptor targeted liposome caused the complete regression of MDA-MB-468 tumors in mice, probably due to the enhancement of its proapoptotic, antiproliferative and antiangiogenic activities. DISCUSSION: Tumor-targeted RNA replicase-based plasmids hold a strong potential in tumor therapy. PMID- 22296188 TI - Transition-metal-promoted or -catalyzed exocyclic alkyne insertion via zirconacyclopentene with carborane auxiliary: formation of symmetric or unsymmetric benzocarboranes. AB - Reactions of Cp(2)Zr(MU-Cl)(MU-C(2)B(10)H(10))Li(OEt(2))(2) with alkynes R(1)C=CR(2) gave as insertion products zirconacyclopentenes incorporating a carboranyl unit, 1,2-[Cp(2)ZrC(R(1))?C(R(2))]-1,2-C(2)B(10)H(10) (1). Treatment of 1 with another type of alkyne R(3)C=CR(4) in the presence of stoichiometric amounts of NiCl(2) and FeCl(3) or a catalytic amount of NiCl(2) afforded symmetric or unsymmetric benzocarboranes. The regioselectivity was dominated by the polarity of the corresponding alkynes. These reactions could also be carried out in one pot, leading to the equivalent of a three-component [2 + 2 + 2] cycloaddition of carboryne and two different alkynes promoted by transition metals. A reaction mechanism was proposed after the isolation and structural characterization of the key intermediate nickelacycle. These results show that nickel complexes are more reactive than the iron ones toward the insertion of alkynes but that the latter do not initiate the trimerization of alkynes, making the insertion of activated alkynes possible. This work also demonstrates that a catalytic amount of nickel works as well as a stoichiometric amount of nickel in the presence of excess FeCl(3) for the reactions. Such a catalytic reaction may shed some light on the development of zirconocene-based catalytic reactions. PMID- 22296187 TI - Suboptimal patterns of provider initiated HIV testing and counselling, antiretroviral therapy eligibility assessment and referral in primary health clinic attendees in Blantyre, Malawi. AB - OBJECTIVE: To understand reasons for suboptimal and delayed uptake of antiretroviral therapy (ART) by describing the patterns of HIV testing and counselling (HTC) and outcomes of ART eligibility assessments in primary clinic attendees. METHODS: All clinic attendances and episodes of HTC were recorded at two clinics in Blantyre. A cohort of newly diagnosed HIV-positive adults (>15 years) was recruited and exit interviews undertaken. Logistic regression models were constructed to investigate factors associated with referral to start ART. Qualitative interviews were conducted with providers and patients. RESULTS: There were 2398 episodes of HTC during 18,021 clinic attendances (13.3%) between January and April 2011. The proportion of clinic attendees undergoing HTC was lowest in non-pregnant women (6.3%) and men (8.5%), compared with pregnant women (47.2%). Men had more advanced HIV infection than women (79.7% WHO stage 3 or 4 vs. 56.4%). Problems with WHO staging and access to CD4 counts affected ART eligibility assessments; only 48% completed ART eligibility assessment, and 54% of those reporting WHO stage 3/4 illnesses were not referred to start ART promptly. On multivariate analysis, HIV-positive pregnant women were significantly less likely to be referred directly for ART initiation (adjusted OR: 0.29, 95% CI: 0.13-0.63). CONCLUSIONS: These data show that provider initiated testing and counselling (PITC) has not yet been fully implemented at primary care clinics. Suboptimal ART eligibility assessments and referral (reflecting the difficulties of WHO staging in primary care) mean that simplified eligibility assessment tools are required to reduce unnecessary delay and attrition in the pre-ART period. Simplified initiation criteria for pregnant women, as being introduced in Malawi, should improve linkage to ART. PMID- 22296190 TI - Inflammation and related biomarkers in cardiovascular disease. PMID- 22296191 TI - Skeletal muscle biomarkers in heart disease. PMID- 22296192 TI - Cathepsin S as a biomarker: where are we now and what are the future challenges? PMID- 22296193 TI - Practical use of natriuretic peptide measurement: questionnaire results from general practitioners and cardiologists. AB - AIMS: To elucidate the knowledge regarding B-type natriuretic peptide (BNP)/N terminal proBNP (NT-proBNP) measurement among doctors using this biomarker. MATERIALS & METHODS: We performed a questionnaire-based study on the use of BNP/NT-proBNP measurement among doctors; 21 general practitioners and 23 randomly chosen doctors at cardiology departments were interviewed. RESULTS: 12 general practitioners (57%) answered 'yes', eight (38%) answered 'no' and one (5%) was 'undecided' for use of BNP/NT-proBNP measurement to exclude a diagnosis of heart failure. Among cardiologists, 11 (48%) answered 'yes', ten (43%) answered 'no' and two (9%) were 'undecided' (no difference between groups, p = 0.56). The majority of doctors were familiar with BNP/NT-proBNP being affected by age but were unaware of the impact of gender and obesity. CONCLUSION: We propose that BNP/NT-proBNP measurement results should be supplied with age- and gender-related cut-off values, along with a notion of the negative predictive value and other parameters affecting the concentration in plasma. PMID- 22296194 TI - High-sensitive C-reactive protein: universal prognostic and causative biomarker in heart disease? AB - C-reactive protein (CRP), a pentraxin protein, is an established marker of acute phase reactions. There is some experimental evidence that the CRP molecule could be causative in all stages of atherosclerotic disease starting from endothelial dysfunction, continuing to plaque formation and destabilization, and to atherothrombotic complications. However, each claim of causality has elicited a counterpoint argument, and Mendelian randomization studies have confidently shown that the concentration of CRP is unlikely to be causative. Meta-analyses have attributed a 1.5-1.7-fold risk to one standard deviation increase of high sensitive CRP (a high-sensitivity CRP assay) for major cardiovascular events after adjustments for classical risk factors. Additional adjustments for metabolic factors reduced the risk to approximately 1.2-1.4-fold, which is still significant. Of interest, high-sensitive CRP also predicted all-cause and cancer mortality. Driven by the JUPITER trial that showed a benefit on outcome for treatment with rosuvastatin in primary prevention, treatment has been recommended in patients with a moderate Framingham Risk Score with a high-sensitive CRP of >2 mg/l. However, adding CRP to risk charts and biomarker panels mostly yielded small and inconsistent improvements. PMID- 22296195 TI - Cardiovascular metabolic syndrome: mediators involved in the pathophysiology from obesity to coronary heart disease. AB - Patients with obesity and diabetes mellitus are at increased risk for cardiovascular events and have a higher cardiovascular morbidity and mortality. This worse prognosis is partly explained by the late recognition of coronary heart disease in these patients, due to the absence of symptoms. Early identification of coronary heart disease is vital, to initiate preventive medical therapy and improve prognosis. At present, with the use of cardiovascular risk models, the identification of coronary heart disease in these patients remains inadequate. To this end, biomarkers should improve the early identification of patients at increased cardiovascular risk. The first part of this review describes the pathophysiologic pathway from obesity to coronary heart disease. The second part evaluates several mediators from this pathophysiologic pathway for their applicability as biomarkers for the identification of coronary heart disease. PMID- 22296196 TI - Future potential biomarkers for postinterventional restenosis and accelerated atherosclerosis. AB - New circulating and local arterial biomarkers may help the clinician with risk stratification or diagnostic assessment of patients and selecting the proper therapy for a patient. In addition, they may be used for follow-up and testing efficacy of therapy, which is not possible with current biomarkers. Processes leading to postinterventional restenosis and accelerated atherosclerosis are complex due to the many biological variables mediating the specific inflammatory and immunogenic responses involved. Adequate assessment of these processes requires different and more specific biomarkers. Postinterventional remodeling is associated with cell stress and tissue damage causing apoptosis, release of damage-associated molecular patterns and upregulation of specific cytokines/chemokines that could serve as suitable clinical biomarkers. Furthermore, plasma titers of pathophysiological process-related (auto)antibodies could aid in the identification of restenosis risk or lesion severity. This review provides an overview of a number of potential biomarkers selected on the basis of their role in the remodeling process. PMID- 22296197 TI - Cardiac myosin binding protein-C: a potential early-stage, cardiac-specific biomarker of ischemia-reperfusion injury. PMID- 22296200 TI - Correlation of peripheral arterial blood flow with plasma chemerin and VEGF in diabetic peripheral vascular disease. AB - AIMS: Progressive vasodegeneration in microvascular beds is the major underlying factor in initiation and progression of diabetic complications. Chemerin shows a strong correlation with various facets of the metabolic syndrome, which is associated with dysregulated angiogenesis. VEGF is shown to have an angiogenic role in certain cardiovascular risk factors, including diabetes. Ankle/brachial index is a known approach for assessing lower-limb peripheral vascular disease. This study aimed to elucidate the correlation of ankle/brachial index as a marker of peripheral blood flow with biomarkers of angiogenesis, plasma chemerin and VEGF, in diabetic peripheral vascular disease. MATERIALS & METHODS: Ninety age- and sex-matched females were enrolled in the study: 30 were controls, while 60 had Type 2 diabetes, of whom 30 had controlled diabetes (group II) and 30 had diabetes with peripheral vascular disease (group III) diagnosed by an abnormal ankle/brachial index. Plasma levels of chemerin and VEGF were measured. RESULTS: There was a significant decrease of the ankle/brachial index and significant increase in plasma chemerin and VEGF in diabetic patients with peripheral vascular disease (p < 0.05). A positive correlation was observed between ankle/brachial index, plasma chemerin and VEGF in diabetic patients with peripheral vascular disease. Linear regression analysis revealed that neither chemerin nor VEGF were predictors for ankle/brachial index in diabetic peripheral vascular disease. CONCLUSION: This study elucidates, for the first time, the rise of plasma levels of chemerin and VEGF, and their positive correlation with ankle/brachial index in diabetic peripheral vascular disease. These findings denote their angiogenic effect of improving the peripheral blood flow in diabetic peripheral vascular disease. Further studies are warranted to examine the exact role of these two biomarkers in diabetic vasculopathy. PMID- 22296201 TI - Genetic variation of IL-12B (+1188 region) is associated with its decreased circulating levels and susceptibility to Type 2 diabetes. AB - BACKGROUND: Type 2 diabetes mellitus is one of the most common types of endocrine disease and the immune system plays a predominant role in its pathogenesis. AIMS: The present study aimed to examine known gene polymorphisms within IL-12B (+1188) region and its circulating serum levels in Type 2 diabetic patients from the southeastern region of Iran and compare them with unrelated controls. MATERIALS & METHODS: In this clinical study, peripheral blood was collected from 114 Type 2 diabetic patients and 100 healthy controls. Serum levels of IL-12B were measured by ELISA. Genomic DNA was extracted from peripheral blood samples and polymorphisms at the +1188 position of the IL-12B gene were assessed using PCR restriction fragment-length polymorphism. RESULTS: Our findings demonstrated that the AA genotype and the A allele of IL-12B were increased significantly in Type 2 diabetic patients when compared with controls. Our results also showed that the circulating levels of IL-12B were significantly decreased in Type 2 diabetic patients when compared with controls. CONCLUSION: According to the findings of the current study, we concluded that IL-12B and its +1188 polymorphism may play a prominent role in the pathogenesis of Type 2 diabetes. Further replicative investigations using a larger sample size are essential to identify additional IL 12B genetic variants associated with a risk of Type 2 diabetes. PMID- 22296202 TI - Circulating levels of resistin, IL-6 and lipid profile in elderly patients with ischemic heart disease with and without diabetes. AB - BACKGROUND: The cytokines that act as inflammatory hormones show a role in coronary atherosclerotic disease. AIMS: This study aimed to measure serum resistin, IL-6 levels and lipid profile in nondiabetic controls, diabetics, and ischemic heart disease subjects with and without diabetes. Association between resistin and IL-6 was also determined. MATERIALS & METHODS: In this comparative cross-sectional study, 147 subjects were selected, aged between 40 and 70 years. Subjects were divided into four groups as mentioned above. Plasma glucose was measured using the gluco-oxidase method. Lipid profile levels were measured using standard enzymatic methods. Levels of resistin and IL-6 were determined by ELISA. RESULTS: Out of 147 patients, 36 were controls and 111 were cases. Serum resistin and IL-6 levels increased significantly in diabetics (23.4 +/- 0.74 ng/ml and 73.1 +/- 2.57 ng/ml, respectively) and nondiabetics with ischemic heart disease (14.1 +/- 0.51 ng/ml and 66.2 +/- 2.08 ng/ml, respectively) compared with diabetics and nondiabetic controls. Positive correlations were found between IL-6 and resistin, and a significant positive correlation was shown in ischemic heart disease groups (r = 0.659; p = 0.001). CONCLUSION: This study shows that the plasma resistin and IL-6 concentrations increased significantly in patients with ischemic heart disease with and without diabetes. This shows that there is a possible role of resistin and IL-6 in inflammatory processes, especially in atherosclerosis. PMID- 22296203 TI - Association of Thr420Lys polymorphism in DBP gene with fat-soluble vitamins and low radial bone mineral density in postmenopausal Thai women. AB - AIMS: To investigate the genetic markers for osteoporosis bone mineral density by the genotyping of rs7041, rs4588 and rs1352845 in the DBP gene with either bone mineral density or serum 25-hydroxycholecalciferol, retinol and alpha-tocopherol, among 365 postmenopausal Thai women. MATERIALS & METHODS: The DBP genotypes were analyzed by a PCR restriction fragment-length polymorphism method. Serum 25 hydroxycholecalciferol was assessed using a commercial chemiluminescent immunoassay. Serum retinol and alpha-tocopherol were measured by reverse-phase high-performance liquid chromatography. RESULTS: After adjustment for age >50 years, elder Thai subjects with low BMI (<=25 kg/m(2)) and carrying the rs4588 CC genotype had a higher risk of radial bone mineral density osteoporosis (odds ratio: 6.29; p = 0.048). The rs1352845 genotype also had a statistical association with total hip bone mineral density; however, it disappeared after adjustment for age and BMI. No association was found in fat-soluble vitamins with bone mineral density. CONCLUSION: DBP genotypes may influence the osteoporosis bone mineral density in postmenopausal Thai women. PMID- 22296204 TI - Clinical implications of the detection of circulating tumor cells in breast cancer patients. AB - The detection of disseminated tumor cells in bone marrow is a common phenomenon seen in 30-40% of primary breast cancer patients. The presence of disseminated tumor cells at diagnosis as well as the persistence of disseminated tumor cells is strongly associated with poor clinical outcome. Since bone marrow biopsies are not well tolerated by many patients, the evaluation of circulating tumor cells in the blood might become a desired alternative. Circulating tumor cells are routinely detected, depending on stage of the disease and methodology, in 10-80% of breast cancer patients. Recent studies have shown a prognostic potential of circulating tumor cells in both primary and metastatic settings. The evaluation of circulating tumor cells may become one of the crucial markers for prediction of survival and therapy monitoring, and its characterization might enable specific targeting of minimal residual, and metastatic disease. PMID- 22296205 TI - Use of cerebrospinal fluid biomarkers in clinical trials for schizophrenia and depression. AB - The pharmaceutical industry is increasingly using biomarkers in clinical trials in order to determine if new drug candidates are displaying the expected pharmacological properties and to give early indications if they are showing efficacy or unexpected toxicity. This is especially true for the development of new drug candidates for psychiatric disorders such as schizophrenia and depression, where it is imperative to understand whether the drug is reaching the brain and acting on the target. A particular challenge for biochemical biomarkers used to determine centrally mediated activity is the relative inaccessibility of the brain to direct sampling of cells or tissues. As a result, the use of biomarkers located in the cerebrospinal fluid and in close contact with the interstitial fluid of the brain has risen in prominence. Cerebrospinal fluid biomarkers allow for the analysis of biochemical changes that reflect pharmacological activity or that may be related to the disease. In the area of psychiatric disorders, many studies have utilized biochemical biomarkers in the cerebrospinal fluid for gaining pharmacodynamic or disease modification information. This review summarizes many of these efforts, and identifies challenges and opportunities for utilizing biomarkers for new drug candidates targeting psychiatric disorders. PMID- 22296207 TI - Investigation of aqueous-phase photooxidation of glyoxal and methylglyoxal by aerosol chemical ionization mass spectrometry: observation of hydroxyhydroperoxide formation. AB - Aqueous-phase processing of glyoxal (GLY) and methylglyoxal (MG) produces highly oxygenated, less volatile organic acids that can contribute to SOA formation and aging. In this study, aerosol chemical ionization mass spectrometry (aerosol CIMS) is employed to monitor aqueous-phase photooxidation of GLY and MG. Using iodide (I(-)) as the reagent ion, aerosol CIMS can simultaneously detect important species involved in the reactions: organic acids, peroxides, and aldehydes, so that the reconstructed total organic carbon (TOC) concentrations from aerosol CIMS data agree well with offline TOC analysis. This study also reports the first direct detection of hydroxyhydroperoxide (HHP) formation from the reaction of H(2)O(2) with GLY or MG. The formation of HHPs is observed to be reversible and an estimate of their equilibrium constants is made to be between 40 and 200 M(-1). Results of this study suggest that HHPs can form additional formic acid and acetic acid via photooxidation and regenerate GLY or MG during photooxidation, compensating their loss. HHP formation needs to be further studied for inclusion in aqueous-phase chemical models given that it may affect the aqueous partitioning of carbonyls in the atmosphere. PMID- 22296208 TI - Assessment of exposure to drugs of abuse during pregnancy by hair analysis in a Mediterranean island. AB - AIMS: This study aims to estimate the prevalence of drug use by pregnant women living in Ibiza, using structured interviews and biomarkers in maternal hair. In addition, the potentially detrimental effects of maternal drug abuse on their newborns were investigated. Ibiza has a large international night-life resort associated with clubs, music and use of recreational drugs. DESIGN, SETTING AND PARTICIPANTS: Hair samples were collected prospectively from January to March 2010 from a cohort of consecutive mothers after giving birth in the Hospital Can Misses in Ibiza. MEASUREMENTS: Opiates, cocaine, cannabis, methadone, amphetamines, 3,4-methylenedioxymethamphetamine (MDMA) and their metabolites were detected in a 3-cm-long proximal segment of maternal hair corresponding to the last trimester of pregnancy by gas chromatography coupled to mass spectrometry (n = 107). Data on socio-demographic characteristics and on tobacco, alcohol, drugs of prescription and drugs of abuse consumption during pregnancy were collected using a structured questionnaire. FINDINGS: Hair analysis showed an overall 16% positivity for drugs of abuse in the third trimester of pregnancy, with a specific prevalence of cannabis, cocaine, MDMA and opiates use of 10.3, 6.4, 0.9 and 0%, respectively. In the questionnaires, only 1.9% of mothers declared using drugs of abuse during pregnancy. Gestational drug of abuse consumption was associated with active tobacco smoking, a higher number of smoked cigarettes and the mother being Spanish. CONCLUSIONS: Illicit drug use is substantially under reported among pregnant women living in Ibiza, particularly among Spanish nationals. Voluntary, routine objective biological toxicology screening should be considered as part of routine examinations in antenatal clinics on this Mediterranean island. PMID- 22296209 TI - An unusual case of Gitelman's syndrome with hypercalcemia. AB - We reported a case of a 41-year-old woman who had been diagnosed with Gitelman's syndrome since the age of 31 years. The diagnosis was established by the typical biochemical pictures including renal wasting hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis, and hyperreninemic hyperaldosteronism. She had normal blood pressure and had never used diuretics. She had a sibling with similar syndrome. The patient was treated with oral potassium and magnesium supplementation. She began to have hypercalcemia at the age of 39 years. The diagnostic approach to hypercalcemia became more complicated because of normal parathyroid hormone levels and underlying hypocalciuria due to Gitelman's syndrome. Thorough evaluation eventually identified primary hyperparathyroidism as the cause of hypercalcemia. To our best knowledge, this is the first report of combined occurrence of Gitelman's syndrome and primary hyperparathyroidism in the literature. PMID- 22296210 TI - New NIRS calibrations for fiber fractions reveal broad genetic variation in Brassica napus seed quality. AB - Near-infrared reflectance spectroscopy (NIRS) calibrations were developed for the estimation of neutral detergent fiber (NDF), acid detergent fiber (ADF), and acid detergent lignin (ADL) in intact seeds of oilseed rape ( Brassica napus ). A set of 338 diverse winter oilseed rape genotypes showing broad variation for seed color was used as a basis for the new calibrations. Different calibrations were generated for 10 or 1 mL seed volumes, respectively. In both seed volumes good coefficients of determination for external validation (R(2)) of the calibrations were obtained for ADL, the major antinutritional fiber fraction in oilseed rape meal, and adequate calibrations for NDF and ADF. Evaluation of diverse B. napus germplasm with the new calibrations revealed a surprisingly broad variation in contents of ADL in dark-seeded oilseed rape. The ability to use NIRS for efficient selection of low-fiber genotypes, irrespective of seed color, represents an important breakthrough in breeding for improved nutritional quality of seed extraction meals from oilseed rape. PMID- 22296211 TI - Earlier initiation of antiretroviral therapy, increased tuberculosis case finding and reduced mortality in a setting of improved HIV care: a retrospective cohort study. AB - OBJECTIVES: High early mortality after antiretroviral therapy (ART) initiation in resource-limited settings is associated with low baseline CD4 cell counts and a high burden of opportunistic infections. Our large urban HIV clinic in Uganda has made concerted efforts to initiate ART at higher CD4 cell counts and to improve diagnosis and care of patients coinfected with tuberculosis (TB). We sought to determine associated treatment outcomes. METHODS: Routinely collected data for all patients who initiated ART from 2005 to 2009 were analysed. Median baseline CD4 cell counts by year of ART initiation were compared using the Cuzick test for trend. Mortality and TB incidence rates in the first year of ART were computed. Hazard ratios (HRs) were calculated using multivariable Cox proportional hazards models. RESULTS: First-line ART was initiated in 7659 patients; 64% were women, and the mean age was 37 years (standard deviation 9 years). Median baseline CD4 counts increased from 2005 to 2009 [82 cells/MUL (interquartile range (IQR) 24, 153) to 148 cells/MUL (IQR 61, 197), respectively; P<0.001]. The mortality rate fell from 6.5/100 person-years at risk (PYAR) [95% confidence interval (CI) 5.5 7.6 PYAR] to 3.6/100 PYAR (95% CI 2.2-5.8 PYAR). TB incidence rates increased from 8.2/100 PYAR (95% CI 7.1-9.5 PYAR) to 15.6/100 PYAR (95% CI 12.4-19.7 PYAR). A later year of ART initiation was independently associated with decreased mortality (HR 0.91; 95% CI 0.83-1.00; P=0.04). CONCLUSIONS: Baseline CD4 cell counts have increased over time and are associated with decreased mortality. Additional reductions in mortality might be a result of a better standard of care and increased TB case finding. Further efforts to initiate ART earlier should be prioritized even in a setting of capped or reduced funding for ART programmes. PMID- 22296212 TI - An alternative approach to para-C-H arylation of phenol: palladium-catalyzed tandem gamma-arylation/aromatization of 2-cyclohexen-1-one derivatives. AB - An efficient approach to prepare para-aryl phenols has been developed by using a Pd-catalyzed tandem gamma-arylation/aromatization of 2-cyclohexen-1-one derivatives with aryl bromides. This approach provides various p-aryl phenols from the phenol surrogates, 2-cyclohexen-1-one derivatives, in a single reaction step on the basis of C-H arylation. PMID- 22296213 TI - Quick, controlled synthesis of ultrathin Bi2Se3 nanodiscs and nanosheets. AB - Ultrathin (4-6 nm) single-crystal Bi(2)Se(3) nanodiscs and nanosheets were synthesized through a simple and quick solution process. The growth mechanism was investigated in detail. Crystal seeds grew via 2D self-attachment of small nanoparticles followed by epitaxial recrystallization into single crystals. The lateral dimension of the nanodiscs increased and their shape changed from circles to hexagons as the reaction temperature increased. Positively charged polymer surfactants greatly enlarged the lateral dimension to produce nanosheets with uniform thickness. PMID- 22296214 TI - Spectrofluorescence of skin and hair. AB - There are numerous chromophores present throughout the strata of human skin, which present many challenges and opportunities to probe molecular events. Fluorescence spectroscopy is principally employed to identify important biochemical components of the skin including endogenous tryptophan, tyrosine, pepsin-digestible collagen cross-links, collagenase-digestible collagen cross links, NADH, etc. Over the last 15 years, many advances in instrument technology have been introduced allowing for much faster data acquisition with spectrofluorometers. As a result, a series of spectrofluorescence emission scans can be generated for a range of excitation wavelengths, or vice versa (excitation scans for a range of emission wavelengths), quickly to generate excitation emission matrices. In this work, we constructed an endogenous fingerprint of fluorescent compounds present in skin, hair and nail tissues by employing a range of excitation wavelengths from 270 to 450 nm with a resolution of 2 nm. As a result, we generated surface plots of fluorescence emission as a function of excitation and emission wavelengths. From these data, we identified the predominant fluorescent chromophores in each tissue. We examined several sources of skin including in vivo human and ex vivo pig, sheep, goat and cow skin. We also analysed various types of mature hair characterized by the degree of melanin content. These analyses provided us with a fundamental understanding of the effects of melanin distribution in hair fibres and aided with the identification of fluorophores present in hair. PMID- 22296215 TI - ImmunoMembrane: a publicly available web application for digital image analysis of HER2 immunohistochemistry. AB - AIMS: Assessment of the human epidermal growth factor receptor 2 (HER2) with immunohistochemistry (IHC) is routine practice in clinical pathology laboratories. Visual classification of the staining reaction (usually into 0/1+, 2+ or 3+) is subjective and prone to significant inter- and intra-observer variation. In this study, we describe ImmunoMembrane, an easy-to-use HER2 IHC analysis software, which is freely available as a web application, requiring no download or installation. METHODS AND RESULTS: ImmunoMembrane uses colour deconvolution for stain separation and a customized algorithm for cell membrane segmentation. A quantitative score (IM-score, 0-20 points) is generated according to the membrane staining intensity and completeness. Specimens are classified into 0/1+, 2+ or 3+ based on IM-score cut-offs defined using a training set. The classification and membrane segmentation are presented as a pseudo-coloured overlay image. With a validation set (144 HercepTest((r)) -stained whole tissue sections), ImmunoMembrane matched well with the pathologist's visual classification (weighted kappa kappa(w) =0.80), as well as fluorescence in-situ hybridization (FISH) (IHC disagreement 3.5%, n=144) and chromogenic in-situ hybridization (CISH) (IHC disagreement 2.8%, n=144). CONCLUSIONS: We anticipate that publicly available web applications, such as ImmunoMembrane, will accelerate the adoption of automated image analysis in clinical diagnostics of HER2 IHC. ImmunoMembrane is freely accessible at: http://jvsmicroscope.uta.fi/immunomembrane/. PMID- 22296216 TI - Simultaneous quantification of polymeric and surface active stabilizers of nanosuspensions by using near-infrared spectroscopy. AB - Nanosuspension technology is an attractive approach for the formulation and solubility enhancement of poorly water-soluble drug compounds. The technology requires adequate excipients for stabilizing the suspensions during nanogrinding and storage. This study aimed at establishing a near-infrared (NIR) method for assaying simultaneously the two nanoparticle stabilizers, sodium dodecyl sulphate (SDS) and hydroxypropylcellulose (HPC), in miconazole nanosuspensions. Second derivative of NIR signals was used to establish calibration curves in concentration ranges of interest of SDS (0.03-0.3%) and HPC (0.75-7.5%). The suitability and applicability of the NIR method was verified by evaluating the linearity, accuracy, precision, and specificity of the obtained data. The method was then used to quantify indirectly the amount of SDS and HPC adsorbed onto miconazole nanoparticles. Within the concentration range of interest, SDS adsorption increased up to 122 ug/m(2) (4.2 * 10(-7) mol/m(2)) with increasing SDS concentration, and HPC adsorption was in the range of 800-1000 ug/m(2) (21-27 * 10(-7) mol/m(2)) for nanosuspensions containing nominally 5% HPC and 12.5% or 20% miconazole. Interestingly, some of the adsorbed HPC was displaced upon increase of SDS concentration and adsorption. The data were also confirmed by surface tension measurements of aqueous solutions of SDS and HPC and nanosuspension supernatants. The availability of a fast and nondestructive method for quantifying simultaneously the adsorption of two stabilizers onto nanoground particles may not only speed up nanosuspension development, but also provide insight into the mechanisms of nanoparticle stabilization regarding competitive adsorption and electrostatic versus steric stabilization. PMID- 22296217 TI - Synthesis and calorimetric, spectroscopic, and structural characterization of isocyanide complexes of trialkylaluminum and tri-tert-butylgallium. AB - Addition of tert-butylisocyanide or 2,6-dimethylphenylisocyanide to a solution of trialkylaluminum or trialkylgallium results in formation of complexes R(3)M.C=N(t)Bu (M = Al, R = Me (1), Et (2), (i)Bu (3), (t)Bu (4); M = Ga, R = (t)Bu (9)) or R(3)M.C=N(2,6-Me(2)C(6)H(3)) (M = Al, R = Me (5), Et (6), (i)Bu (7), (t)Bu (8); M = Ga, R = (t)Bu (10)), respectively. Complexes 1, 4, 5, and 8 10 are isolated as solids, whereas the triethylaluminum and triisobutylaluminum adducts 2, 3, 6, and 7 are viscous oils. Complexes 1-10 were characterized by NMR ((1)H, (13)C) and IR spectroscopies, and the molecular structures of 4, 5, and 8 10 were also determined by X-ray crystallography. The frequency of the C=N stretch of the isocyanide increased by 58-91 cm(-1) upon complexation, consistent with coordination of the isocyanide as a sigma donor. Enthalpies of complex formation for 1-10 were determined by isothermal titration calorimetry. Enthalpy data suggest the following order of decreasing Lewis acidity: (t)Bu(3)Al ? (i)Bu(3)Al >= Me(3)Al ~ Et(3)Al ? (t)Bu(3)Ga. In the absence of oxygen and protic reagents, the reported complexes do not undergo insertion or elimination reactions upon heating their benzene-d(6) solutions to 80 degrees C. PMID- 22296219 TI - Giant magnetoelastic effect at the opening of a spin-gap in Ba3BiIr2O9. AB - As compared to 3d (first-row) transition metals, the 4d and 5d transition metals have much more diffuse valence orbitals. Quantum cooperative phenomena that arise due to changes in the way these orbitals overlap and interact, such as magnetoelasticity, are correspondingly rare in 4d and 5d compounds. Here, we show that the 6H-perovskite Ba(3)BiIr(2)O(9), which contains 5d Ir(4+) (S = 1/2) dimerized into isolated face-sharing Ir(2)O(9) bioctahedra, exhibits a giant magnetoelastic effect, the largest of any known 5d compound, associated with the opening of a spin-gap at T* = 74 K. The resulting first-order transition is characterized by a remarkable 4% increase in Ir-Ir distance and 1% negative thermal volume expansion. The transition is driven by a dramatic change in the interactions among Ir 5d orbitals, and represents a crossover between two very different, competing, ground states: one that optimizes direct Ir-Ir bonding (at high temperature), and one that optimizes Ir-O-Ir magnetic superexchange (at low temperature). PMID- 22296218 TI - Effect of vitamin C deficiency during postnatal development on adult behavior: functional phenotype of Gulo-/- knockout mice. AB - Organisms using oxygen for aerobic respiration require antioxidants to balance the production of reactive oxygen species during metabolic processes. Various species--including humans and other primates--suffer mutations in the GULO gene encoding L-gulono-gamma-lactone oxidase; GULO is the rate-limiting enzyme in the biosynthesis of ascorbate, an important cellular antioxidant. Animals lacking the ability to synthesize vitamin C develop scurvy without dietary supplementation. The Gulo-/- knockout (KO) mouse requires oral supplemental vitamin C; without this supplementation the animal dies with a scorbutic condition within several weeks. Vitamin C is known to be most abundant in the brain, where it is believed to play important roles in neuroprotection, neurotransmission and neuromodulation. We therefore hypothesized that ascorbate deficiency in Gulo-/- KO mice might lead to an abnormal behavioral phenotype. We established the amount of ascorbate in the drinking water (220 ppm) necessary for generating a chronic low-ascorbate status in the brain, yet clinically the mice appeared healthy throughout 100 days postpartum at which time all behavioral-phenotyping tests were completed. Compared with Gulo+/+ wild-type littermates, ascorbate-deficient Gulo-/- mice were found to be less active in moving in their environment; when in water, these mice swam more slowly in some tests, consistent with a mild motor deficit. We found no evidence of cognitive, anxiety or sensorimotor-gating problems. Despite being less active, Gulo-/- mice exhibited exaggerated hyperactivity to the dopaminergic agonist methamphetamine. The subnormal movement, combined with hypersensitivity to a dopamine agonist, point to developmental ascorbate deficiency causing long-term striatal dysfunction. PMID- 22296220 TI - A comparative study of byssogenesis on zebra and quagga mussels: the effects of water temperature, salinity and light-dark cycle. AB - The quagga mussel (Dreissena rostriformis bugensis) and zebra mussel (Dreissena polymorpha) are invasive freshwater bivalves in Europe and North America. The distribution range of both Dreissena species is still expanding and both species cause major biofouling and ecological effects, in particular when they invade new areas. In order to assess the effect of temperature, salinity and light on the initial byssogenesis of both species, 24 h re-attachment experiments in standing water were conducted. At a water temperature of 25 degrees C and a salinity of 0.2 psu, the rate of byssogenesis of D. polymorpha was significantly higher than that of D. rostriformis bugensis. In addition, byssal thread production by the latter levelled out between 15 degrees C and 25 degrees C. The rate of byssogenesis at temperatures<25 degrees C was similar for both species. Neither species produced any byssal threads at salinities of 4 psu or higher. At a salinity of 1 psu and a water temperature of 15 degrees C, D. polymorpha produced significantly more byssal threads than D. rostriformis bugensis. There was no significant effect of the length of illumination on the byssogenesis of either species. Overall, D. polymorpha produced slightly more byssal threads than D. rostriformis bugensis at almost all experimental conditions in 24 h re-attachment experiments, but both species had essentially similar initial re-attachment abilities. The data imply that D. rostriformis bugensis causes biofouling problems identical to those of D. polymorpha. PMID- 22296221 TI - Intermittent granulocyte colony-stimulating factor maintains dose intensity after ABVD therapy complicated by neutropenia. AB - INTRODUCTION: Granulocyte Colony-Stimulating Factor (G-CSF) is commonly used to maintain dose intensity in patients receiving ABVD chemotherapy (doxorubicin, bleomycin, vinblastine and dacarbazine) for Hodgkin lymphoma. However, the need for growth factor support is unclear, with studies suggesting that dose intensity can be maintained without G-CSF. Moreover, G-CSF is expensive (pegfilgrastim: EUR 1540/cycle; 300 MUg filgrastim for 7 days: EUR 700/cycle) and is associated with side effects including bone pain and increased risk of bleomycin lung toxicity. Intermittent G-CSF may be an effective compromise, given that the effect of G-CSF on granulocyte precursors in vitro persists for 4-5 days after administration. After promising results of a pilot study, this schedule has been used subsequently in the majority of our patients receiving G-CSF as secondary prophylaxis for ABVD complicated by neutropenia. METHODS: Retrospective analysis of the incidence of febrile neutropenia and treatment delay in a variety of different G-CSF schedules used as secondary prophylaxis in patients receiving ABVD. RESULTS: 848 cycles in 85 consecutive patients were evaluated. Most patients (86%) received G-CSF, generally commenced prophylactically for neutropenia when cycle 1B was due. Intermittent G-CSF (typically given on days 4, 8 and 12) was used in 413 cycles compared with daily or pegylated G-CSF in 99 cycles. In patients receiving intermittent G-CSF, the median neutrophil count, across all cycles, was 7.3 * 10(9) /L (range: 1.4-47.1) when the next scheduled chemotherapy was due. There were two cases of febrile neutropenia (0.45%) and no treatment delays. One patient developed possible bleomycin toxicity. CONCLUSIONS: Intermittent G-CSF is effective in maintaining dose intensity in patients receiving ABVD. PMID- 22296222 TI - Seasonal cycles of species diversity and similarity in a tropical butterfly community. AB - 1. Studies of seasonality in ecological diversity rarely extend over more than a few years, and few studies of seasonal diversity have explicitly investigated the influence of environmental factors on seasonal community composition, especially in tropical communities. 2. Our 10 years of monthly sampling in Amazonian Ecuador yielded 20 996 individuals of 137 fruit-feeding butterfly species. Seasonal cycles of rainfall drive annual cycles in species diversity and community similarity. Undetermined processes operating most strongly during the dry season maintain species diversity and high community similarity across years. 3. Seasonal cycles in community diversity and similarity are superimposed on a gradual decline in similarity between community samples on a decadal time-scale because of long-term changes in species abundances. 4. Monitoring and analysis of changes in community composition over a range of time-scales can be used to refine models of community dynamics by incorporating environmental factors necessary to predict the ecological impact of future climate change. PMID- 22296223 TI - Methyl dynamics flattens barrier to proton transfer in crystalline tetraacetylethane. AB - We analyze the interplay between proton transfer in the hydrogen-bond bridge, O...H...O, and lattice dynamics in the model system tetraacetylethane (TAE) (CH(3)CO)(2)CH?CH(COCH(3))(2) using density functional theory. Lattice dynamics calculations and molecular dynamics simulations are validated against neutron scattering data. Hindrance to the cooperative reorientation of neighboring methyl groups at low temperatures gives a preferred O atom for the bridging proton. The amplitude of methyl torsions becomes larger with increasing temperature, so that the free-energy minimum for the proton becomes flat over 0.2 A. For the isolated molecule, however, we show an almost temperature-independent symmetric double well potential persists. This difference arises from the much higher barriers to methyl torsion in the crystal that make the region of torsional phase space that is most crucial for symmetrization poorly accessible. Consequently, the proton transfer potential remains asymmetric though flat at the base, even at room temperature in the solid. PMID- 22296224 TI - Overcoming low Ge ionization and erosion rate variation for quantitative ultralow energy secondary ion mass spectrometry depth profiles of Si(1-x)Ge(x)/Ge quantum well structures. AB - We specify the O(2)(+) probe conditions and subsequent data analysis required to obtain high depth resolution secondary ion mass spectrometry profiles from multiple Ge/Si(1-x)Ge(x) quantum well structures (0.6 <= x <= 1). Using an O(2)(+) beam at normal incidence and with energies >500 eV, we show that the measured Ge signal is not monotonic with concentration, the net result being an unrepresentative and unquantifiable depth profile. This behavior is attributed to a reduced Ge ionization rate as x approaches 1. At lower beam energies the signal behaves monotonically with Ge fraction, indicating that the Ge atoms are now ionizing more readily for the whole range of x, enabling quantitative profiles to be obtained. To establish the depth scale a point-by-point approach based on previously determined erosion rates as a function of x is shown to produce quantum well thicknesses in excellent agreement with those obtained using transmission electron microscopy. The findings presented here demonstrate that to obtain reliable quantitative depth profiles from Ge containing samples requires O(2)(+) ions below 500 eV and correct account to be taken of the erosion rate variation that exists between layers of different matrix composition. PMID- 22296225 TI - Guidance on vaccination of HIV-infected children in Europe. PMID- 22296226 TI - Accuracy of dermoscopic criteria for the diagnosis of psoriasis, dermatitis, lichen planus and pityriasis rosea. AB - BACKGROUND: Dermoscopy is useful in evaluating skin tumours, but its applicability extends also to the field of inflammatory skin disorders. Plaque psoriasis (PP), dermatitis, lichen planus (LP) and pityriasis rosea (PR) are common inflammatory skin diseases, but little is currently known about their dermoscopic features. OBJECTIVES: To determine and compare the dermoscopic patterns associated with PP, dermatitis, LP and PR and to assess the validity of certain dermoscopic criteria in the diagnosis of PP. METHODS: Patients with PP, dermatitis, LP and PR were prospectively enrolled. The single most recently developed lesion was examined dermoscopically and histopathologically. Variables included vascular morphology, vascular arrangement, background colour, scale colour, scale distribution and presence of Wickham striae. Univariate and adjusted odds ratios were calculated. Discriminant functions were used to plot receiver-operator characteristic curves. RESULTS: Eighty-three patients with PP and 86 patients with either dermatitis, LP or PR were included in the study. Dotted vessels in a regular arrangement over a light red background and white scales were highly predictive for the diagnosis of PP, whereas dermatitis more commonly showed yellow scales and dotted vessels in a patchy arrangement. PR was characterized by yellowish background, dotted vessels and peripheral scales; whitish lines (Wickham striae) were seen exclusively in LP. CONCLUSIONS: PP, LP, PR and dermatitis show specific dermoscopic patterns that may aid their clinical diagnosis. Certain combinations of dermoscopic features can reliably predict the diagnosis of PP. PMID- 22296227 TI - Behavioral and emotional problems among children aged 6-14 years on highly active antiretroviral therapy in Addis Ababa: a cross-sectional study. AB - Children infected with human immunodeficiency virus (HIV) are at particular risk for psychological disturbance. Little is known about the mental health status of children on highly active antiretroviral therapy (HAART). A hospital-based cross sectional study of 318 children aged 6-14 on HAART in Addis Ababa was conducted. Behavioral and emotional problem was assessed using the child behavior check list (CBCL/6-18). Logistic regression analysis was done to select the best subset of predictor variables and determine their association with behavioral and emotional problems. Of the 318 caregivers of children aged 6-14 on HAART, 39.3% of the children had behavioral and emotional problems. Low family monthly income (AOR, 3.44, 95% CI, 1.89-6.25), older age (AOR, 2.27, 95% CI, 1.34-3.83), and parental loss (AOR, 1.89, 95% CI, 1.10-3.25) were found to be determinants of behavioral and emotional problems in the multivariate logistic regression. There is high prevalence of behavioral and emotional problems in children on HAART in Addis Ababa. More support is needed to children from families of low income and those who lost their parents. Further research should be carried out to enhance better understanding and appropriate response to behavioral and emotional problems. PMID- 22296228 TI - Prevalence and correlates of alcohol use disorders in the Singapore Mental Health Survey. AB - AIMS: To establish the prevalence, correlates, comorbidity and treatment gap of alcohol use disorders in the Singapore resident population. DESIGN: The Singapore Mental Health Study is a cross-sectional epidemiological survey. SETTING: A nationally representative survey of the resident (citizens and permanent residents) population in Singapore. PARTICIPANTS: A total of 6616 Singaporean adults aged 18 years and older. MEASUREMENTS: The diagnoses were established using the World Mental Health Composite International Diagnostic Interview (WMH-CIDI) diagnostic modules for life-time and 12-month prevalence of selected mental illnesses including alcohol use disorders. FINDINGS: The life time prevalence of alcohol abuse and alcohol dependence was 3.1% and 0.5%, while the 12-month prevalence of alcohol abuse and alcohol dependence was 0.5% and 0.3%, respectively. The life-time and 12-month prevalence of alcohol use disorders was 3.6% and 0.8%, respectively. Those with alcohol use disorder had significantly higher odds of having major depressive disorder [odds ratio (OR) 3.1] and nicotine dependence (OR 4.5). Compared to the rest of the population, those with an alcohol use disorder had significantly higher odds of having gastric ulcers (OR 3.0), respiratory conditions (OR 2.1) and chronic pain (OR 2.1). Only one in five of those with alcohol use disorder had ever sought treatment. CONCLUSIONS: The prevalence of alcohol use disorders is relatively low in the Singapore adult population. Comorbidity with mental and physical disorders is significant, emphasizing the need to screen people with alcohol use disorders for these comorbidities. PMID- 22296229 TI - LIN28 is selectively expressed by primordial and pre-meiotic germ cells in the human fetal ovary. AB - Germ cell development requires timely transition from primordial germ cell (PGC) self-renewal to meiotic differentiation. This is associated with widespread changes in gene expression, including downregulation of stem cell-associated genes, such as OCT4 and KIT, and upregulation of markers of germ cell differentiation and meiosis, such as VASA, STRA8, and SYCP3. The stem cell expressed RNA-binding protein Lin28 has recently been demonstrated to be essential for PGC specification in mice, and LIN28 is expressed in human germ cell tumors with phenotypic similarities to human fetal germ cells. We have therefore examined the expression of LIN28 during normal germ cell development in the human fetal ovary, from the PGC stage, through meiosis to the initiation of follicle formation. LIN28 transcript levels were highest when the gonad contained only PGCs, and decreased significantly with increasing gestation, coincident with the onset of germ cell differentiation. Immunohistochemistry revealed LIN28 protein expression to be germ cell-specific at all stages examined. All PGCs expressed LIN28, but at later gestations expression was restricted to a subpopulation of germ cells, which we demonstrate to be primordial and premeiotic germ cells based on immunofluorescent colocalization of LIN28 and OCT4, and absence of overlap with the meiosis marker SYCP3. We also demonstrate the expression of the LIN28 target precursor pri-microRNA transcripts pri-LET7a/f/d and pri-LET-7g in the human fetal ovary, and that expression of these is highest at the PGC stage, mirroring that of LIN28. The spatial and temporal restriction of LIN28 expression and coincident peaks of expression of LIN28 and target pri microRNAs suggest important roles for this protein in the maintenance of the germline stem cell state and the regulation of microRNA activity in the developing human ovary. PMID- 22296230 TI - Acute dacryocystitis in a 2-year old child caused by pantoea. AB - A previously healthy 23-month-old girl was admitted for the management of an acute unilateral dacryocystitis following accidental contact with dog faeces. No periocular trauma was reported. Microbiological investigation showed a multiresistant strain of Pantoea species to be the responsible pathogen. The infection responded to a course of oral Clindamycin and Ciprofloxacin, in combination with Chloramphenicol eye drops. This is the first report of an acute dacryocystitis sustained by this microorganism. PMID- 22296231 TI - Postoperative infection rate after dacryocystorhinostomy without the use of systemic antibiotic prophylaxis. AB - PURPOSE: To evaluate the postoperative infection rate after external dacryocystorhinostomy (DCR) without routine systemic antibiotic prophylaxis. METHODS: Retrospective review of case notes, including eye casualty attendances, of 77 patients undergoing 82 consecutive external DCR procedures between 22 December 2006 and 31st December 2009 performed by one of the authors (O. M. Durrani) at a single centre (The Birmingham and Midland Eye Centre, United Kingdom). Patients were given topical Maxitrol eye drops (dexamethasone 0.1%, neomycin 3.5 mg and polymixin B sulphate 10,000 units) three times a day for 1 week postoperatively but no systemic antibiotics. RESULTS: Postoperative infection occurred in one of 82 cases (1.2%, 95% confidence interval 0.03-6.6%). The one case of infection consisted of superficial wound infection only and was managed with oral antibiotics and resolved with a successful outcome. Thirteen out of 87 cases were performed in patients with recurrent dacryocystitis or mucocoeles; none of these cases were complicated by postoperative infection. CONCLUSIONS: Postoperative infection after external DCR without the use of systemic antibiotics is uncommon. Assuming that oral antibiotics are 80% effective at treating postoperative infection, for routine prophylaxis, the number needed to treat to prevent one infection would be 104. Taking the upper confidence limit of 6.6%, the lower limit of the number needed to treat would be 19. The one case of infection was treated successfully with oral antibiotics and resolved with a successful outcome. These results suggest that the routine use of systemic antibiotic prophylaxis in external DCR may not be justified. PMID- 22296232 TI - Reengineering an azaphilone biosynthesis pathway in Aspergillus nidulans to create lipoxygenase inhibitors. AB - Sclerotiorin, an azaphilone polyketide, is a bioactive natural product known to inhibit 15-lipoxygenase and many other biological targets. To readily access sclerotiorin and analogs, we developed a 2-3 step semisynthetic route to produce a variety of azaphilones starting from an advanced, putative azaphilone intermediate (5) overproduced by an engineered strain of Aspergillus nidulans. The inhibitory activities of the semisynthetic azaphilones against 15 lipoxygenase were evaluated with several compounds displaying low micromolar potency. PMID- 22296233 TI - Stable isotopes of Cu and Zn in higher plants: evidence for Cu reduction at the root surface and two conceptual models for isotopic fractionation processes. AB - Recent reports suggest that significant fractionation of stable metal isotopes occurs during biogeochemical cycling and that the uptake into higher plants is an important process. To test isotopic fractionation of copper (Cu) and zinc (Zn) during plant uptake and constrain its controls, we grew lettuce, tomato, rice and durum wheat under controlled conditions in nutrient solutions with variable metal speciation and iron (Fe) supply. The results show that the fractionation patterns of these two micronutrients are decoupled during the transport from nutrient solution to root. In roots, we found an enrichment of the heavier isotopes for Zn, in agreement with previous studies, but an enrichment of isotopically light Cu, suggesting a reduction of Cu(II) possibly at the surfaces of the root cell plasma membranes. This observation holds for both graminaceous and nongraminaceaous species and confirms that reduction is a predominant and ubiquitous mechanism for the acquisition of Cu into plants similar to the mechanism for the acquisition of iron (Fe) by the strategy I plant species. We propose two preliminary models of isotope fractionation processes of Cu and Zn in plants with different uptake strategies. PMID- 22296234 TI - Application of dietary phenolic biomarkers in epidemiology: past, present, and future. AB - Phenolics are a large group of plant compounds that have been associated with protective health effects against several chronic diseases due to their potential antioxidant, anti-inflammatory, and anticarcinogenic properties. Consequently, in nutritional epidemiology it is essential to make an accurate assessment of phenolic exposure to evaluate their protective activities against human diseases. Self-reported questionnaires and biomarkers are the two main methods used for estimating dietary phenolics. Despite the limitations of self-reported methods, they are still an acceptable and useful measure. Meanwhile, nutritional biomarkers provide an alternative, more accurate measure, but they are expensive, and to date there are few validated biomarkers of phenolic intake. Nowadays, new analytical techniques, using both targeted and untargeted metabolomic approaches, play an important part in the rapid increase in the understanding of phenolic bioavailability and, consequently, have provided new potential biomarkers in small trials. In the near future, these dietary biomarkers should be tested in large epidemiological studies. Furthermore, the use of two independent measures questionnaires and biomarkers-together provides a more thorough analysis of true phenolic exposure. Indeed, the challenge in the long term is to combine the information from biomarkers and self-reported questionnaires to clarify the relationship between dietary phenolics and disease. PMID- 22296235 TI - Training community care workers to provide comprehensive TB/HIV/PMTCT integrated care in KwaZulu-Natal: lessons learnt. AB - OBJECTIVE: To describe a participatory approach to implement and evaluate ways to integrate and train community care workers (CCWs) to enhance collaborative TB/HIV/PMTCT activities, and home-based HIV counseling and testing (HCT) at community level. METHODS: The intervention study was conducted in Sisonke, a rural district of KwaZulu Natal, South Africa. A baseline household (HH) survey was conducted in 11 villages. Six villages were randomly selected into intervention and control clusters. Training was provided first to CCWs from the intervention cluster (IC) followed by the control cluster (CC). Routine monthly data from CCWs were collected from March-December 2010. The data was subjected to bivariate tests. RESULTS: The baseline HH survey revealed that of 3012 HH members visited by CCWs in 2008, 21% were screened for TB symptoms, 7% were visited for TB adherence support and 2% for ART adherence, and 1.5% were counselled on infant feeding options. A total of 89 CCWs were trained. Data show that during the study period in IC, 684 adults were offered HCT by CCWs, 92% accepted HCT and tested and 7% tested HIV-positive and were referred to the clinic for further care. Of 3556 adults served in IC, 44% were screened for TB symptoms and 32% for symptoms of sexually transmitted infections (STIs) and 37% of children were traced as TB contact. Out of 6226 adults served in CC, 10% were screened for TB symptoms and 7% for STI symptoms. The differences in uptake of services between IC and CC were statistically significant (p<0.05). CONCLUSION: The findings of this study suggest higher uptake of TB and STI symptoms screening, TB contact tracing and home based HCT in the intervention clusters. This study suggests that up-skilling CCWs could be one avenue to enhance TB/HIV case finding, TB contact tracing and linkages to care. PMID- 22296236 TI - Small non-mucinous bronchioloalveolar carcinoma with anaplastic lymphoma kinase immunoreactivity: a novel ALK fusion gene? AB - Echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (EML4-ALK) and kinesin family member 5B (KIF5B)-ALK are newly identified transforming fusion oncogenes causing non-small-cell lung cancers. These molecular abnormalities have become detectable using not only molecular biological methods, but also highly sensitive immunohistochemistry. During the immunohistochemical study of ALK expression in adenocarcinoma of the lung, we unexpectedly discovered that a small bronchioloalveolar carcinoma (BAC) showed strong ALK immunoreactivity. However, FISH studies failed to reveal EML4-ALK and KIF5B-ALK fusion genes in this BAC. These findings suggest the possibility that a novel or unknown ALK fusion gene plays a crucial role in BAC development. PMID- 22296239 TI - A comparative study of vitamin E TPGS/HPMC supersaturated system and other solubilizer/polymer combinations to enhance the permeability of a poorly soluble drug through the skin. AB - In transdermal drug delivery systems (TDDS), it is a challenge to achieve stable and prolonged high permeation rates across skin, because the concentration of the drug dissolved in the matrix has to be high in order to maintain zero order release kinetics of the drug. In case of poorly soluble drugs, due to thermodynamic challenges, there is a high tendency for the drug to nucleate immediately after formulating or even during storage. The present study focuses on the efficiency of vitamin E TPGS/HPMC supersaturated solution and other solubilizer/polymer systems to improve the solubility of the drug and inhibit crystal growth in the transdermal formulation. Effect of several solubilizers, for example, Pluronic F-127, vitamin E TPGS and co-solvent, for example, propylene glycol (PG) were studied on the supersaturated systems of ibuprofen as model drug. Various stabilizers such as hydroxylpropyl methylcellulose (HPMC 3 cps) and polyvinylpyrrolidone (PVP K-30) were examined to evaluate their crystal inhibitory effects. Different analytical tools were used in this study to detect the growth of crystals in the systems. Vitamin E TPGS and HPMC 3 cps formulation produced the highest permeation rate of the drug as compared to other systems. In addition, the onset of crystallization time was shown to be longer with this formulation as compared to other solubilizer/polymer combinations. PMID- 22296240 TI - New perspectives on nanomaterial aquatic ecotoxicity: production impacts exceed direct exposure impacts for carbon nanotoubes. AB - Environmental impacts due to engineered nanomaterials arise both from releases of the nanomaterials themselves as well as from their synthesis. In this work, we employ the USEtox model to quantify and compare aquatic ecotoxicity impacts over the life cycle of carbon nanotubes (CNTs). USEtox is an integrated multimedia fate, transport, and toxicity model covering large classes of organic and inorganic substances. This work evaluates the impacts of non-CNT emissions from three methods of synthesis (arc ablation, CVD, and HiPco), and compares these to the modeled ecotoxicity of CNTs released to the environment. Parameters for evaluating CNT ecotoxicity are bounded by a highly conservative "worst case" scenario and a "realistic" scenario that draws from existing literature on CNT fate, transport, and ecotoxicity. The results indicate that the ecotoxicity impacts of nanomaterial production processes are roughly equivalent to the ecotoxicity of CNT releases under the unrealistic worst case scenario, while exceeding the results of the realistic scenario by 3 orders of magnitude. Ecotoxicity from production processes is dominated by emissions of metals from electricity generation. Uncertainty exists for both production and release stages, and is modeled using a combination of Monte Carlo simulation and scenario analysis. The results of this analysis underscore the contributions of existing work on CNT fate and transport, as well as the importance of life cycle considerations in allocating time and resources toward research on mitigating the impacts of novel materials. PMID- 22296241 TI - Early patient experience with an electro-anatomic navigation system dedicated to device lead implantation: feasibility and safety. AB - INTRODUCTION: Fluoroscopy-guided pacing lead placement has well-recognized limitations and risks. We studied the safety and feasibility of using a novel electromagnetic navigation system specifically designed to guide pacemaker and implantable cardioverter defibrillator lead placement. METHODS: Twenty-four patients (mean age of 54+/-34 years) underwent the study protocol; 16 before electrophysiology study and eight before device implantation. The navigational deflectable sheath assembly was introduced via the subclavian vein and advanced to seven prespecified targets within the right heart chambers. The time taken to reach each target site was measured. RESULTS: All seven prespecified targets were successfully reached by 21 of 24 patients (88%). The total time required to complete the study protocol ranged from 3.21 to 15.25 minutes (average 8.9 minutes), with an associated mean fluoroscopy time of 50+/-36 seconds. In three of the 24 patients, this navigation system was successfully used to guide right ventricular pacing lead placement. The average total procedure time for these devices was 97.8 minutes (excluding the study protocol), with an average associated fluoroscopy time of 6.93 minutes. These procedures were well tolerated and no periprocedural complications were noted. CONCLUSIONS: This study suggests that this novel electro-anatomic navigation system is a viable and safe alternative to traditional fluoroscopy-guided lead implantation. Further studies are required to determine the absolute reduction in radiation exposure and increased efficiency relative to current standard fluoroscopic techniques. PMID- 22296242 TI - Synthesis of reported and revised structures of amathamide D and synthesis of convolutamine F, H and lutamide A, C. AB - Total synthesis of the published structure of amathamide D is described. Methyl 2,3,4-tribromo-5-hydroxybenzoate was selected as starting compound because it is readily accessible via acid-mediated Grob fragmentation-aromatization reaction of 1,4,5,6-tetrabromo-7,7-dimethoxybicyclo[2.2.1]hept-5-en-2-one. The aforementioned ester was transformed into the reported structure of amathamide D through methylation of a hydroxyl group and conversion of the ester moiety to a beta aminoethyl side chain. The NMR data of the synthetic compound did not conform to the reported natural product structure possessing contiguously positioned beta aminoethyl side chain, a set of three adjacent bromines, and a methyl ether linkage on the phenyl ring. This prompted us to redefine the natural product structure by synthesizing a product whose spectral data exactly matched with the reported data of amathamide D. The convolutamine H, with completely substituted phenyl ring adorned with an extra methyl ether functional group, has also been synthesized by application of Grob fragmentation-aromatization strategy to 3 (benzyloxy)-1,4,5,6-tetrabromo-7,7-dimethoxybicyclo[2.2.1]hept-5-en-2-one. This approach furnished directly methyl 2,3,4-tribromo-5,6-dimethoxybenzoate, which was converted straightforwardly into convolutamine H. Further, synthesis of convolutamine F and lutamide A and C is also described. PMID- 22296243 TI - Unfairly forgotten member of the iodocarborane family: synthesis and structural characterization of 8-iodo-1,2-dicarba-closo-dodecaborane, its precursors, and derivatives. AB - 8-Iodo-1,2-dicarba-closo-dodecaborane (7) was prepared in three steps starting from decaborane-14 with 20% overall yield. In the presence of nucleophiles, compound 7 undergoes selective removal of the boron vertex in the position para to the iodine substituent to form the anionic nido-carborane 1-iodo-7,8-dicarba nido-undecaborate. Capping of the corresponding dicarbollide dianion with BI(3) led to formation of the new carborane, 3,10-diiodo-1,2-dicarba-closo dodecaborane (15). The same dicarbollide dianion reacts with cobalt and nickel acetylacetonates in anhydrous tetrahydrofuran to form the corresponding bis(dicarbollide) complexes with excellent yields. All compounds were characterized by multinuclear NMR and high-resolution mass spectroscopy. Structures of 2-iododecaborane (2), 8-iodo-1,2-dicarba-closo-dodecaborane (7), 1 ethoxycarbonyl-8-iodo-1,2-dicarba-closo-dodecaborane (10), cesium 1-iodo-7,8 dicarba-nido-undecaborate (13), 3,10-diiodo-1,2-dicarba-closo-dodecaborane (15), and cesium 3,3'-commo-(10-iodo-1,2-dicarba-3-cobalta-closo-dodecaborane)-(10' iodo-1',2'-dicarba-3'-cobalta-closo-dodecaborane) (16) were established by X-ray analysis of single crystals. PMID- 22296245 TI - Synthesis and properties of [9]cyclo-1,4-naphthylene: a pi-extended carbon nanoring. AB - The first synthesis of a pi-extended carbon nanoring, [9]cyclo-1,4-naphthylene ([9]CN), has been achieved. Careful structure-property analyses uncovered a number of unique features of [9]CN that are quite different from those of [9]CPP, a simple carbon nanoring. PMID- 22296244 TI - The C134W (402 C>G) FOXL2 mutation is absent in ovarian gynandroblastoma: insights into the genesis of an unusual tumour. AB - AIMS: Ovarian gynandroblastomas are rare tumours that, by definition, comprise a combination of components resembling both female, typically granulosa cell tumour (GCT), and male, typically Sertoli or Sertoli/Leydig cell tumour (ST/SLT), sex cord/stromal differentiation. The histogenesis of these tumours is unknown and, in view of the very strong association between the C134W (402 C>G) FOXL2 mutation and adult-type GCT, we analysed a series of gynandroblastomas for this mutation. METHODS AND RESULTS: Both components of each lesion were isolated by laser capture microdissection and the C134W (402 C>G) FOXL2 mutation was analysed by polymerase chain reaction sequencing. No mutation was identified in either the GCT or ST/SLT component of six cases, three of which contained adult-type GCT. CONCLUSIONS: This suggests that, despite their similar morphological appearances, the GCT-like component of gynandroblastoma has a different molecular basis from conventional adult-type GCT. This finding underscores a more general principle that morphological similarity does not necessarily indicate molecular identity. PMID- 22296246 TI - Harmonising approaches to realigning dietary recommendations. PMID- 22296247 TI - Relevance of European alignment for micronutrients' recommendation regarding pregnant and lactating women, infants, children and adolescents: an insight into preliminary steps of EURRECA. PMID- 22296248 TI - Critical issues in setting micronutrient recommendations for pregnant women: an insight. AB - The European Micronutrient Recommendations Aligned (EURRECA) Network aims to provide standardized approaches to reveal and beneficially influence variability within the European Union in micronutrient recommendations for vulnerable population groups. Characterization of the 'vulnerability' together with the 'variability' of micronutrient needs represents the first step to creating guidelines for setting micronutrient recommendations within target populations. This paper describes some of the key factors and characteristics relevant to assess micronutrient requirements and formulate recommendations of micronutrients in pregnancy. Nutritional requirements during pregnancy increase to support fetal growth and development as well as maternal metabolism and tissue accretion. Micronutrients are involved in both embryonal and fetal organ development and overall pregnancy outcomes. Several factors may affect directly or indirectly fetal nourishment and the overall pregnancy outcomes, such as the quality of diet including intakes and bioavailability of micronutrients, maternal age, and the overall environment. The bioavailability of micronutrients during pregnancy varies depending on specific metabolic mechanisms because pregnancy is an anabolic and dynamic state orchestrated via hormones acting for both redirection of nutrients to highly specialized maternal tissues and transfer of nutrients to the developing fetus. The timing of prenatal intakes or supplementations of specific micronutrients is also crucial as pregnancy is characterized by different stages that represent a continuum, up to lactation and beyond. Consequently, nutrition during pregnancy might have long-lasting effects on the well-being of the mother and the fetus, and may further influence the health of the baby at a later age. PMID- 22296249 TI - Perinatal folate supply: relevance in health outcome parameters. AB - The importance of physiological supply of folate is well recognized in human health; the crucial roles of folate in one-carbon metabolism for physiological DNA synthesis and cell division, as well as in the conversion of homocysteine (Hcy) to methionine, and subsequently, to S-adenosylmethionine, have been convincingly demonstrated. Improved folate status may reduce the risk of macrocytic anaemia, cardiovascular diseases, neuropsychiatric disorders and adverse pregnancy outcomes. Inadequate folate status results in a decrease in the methylation cycle and in increased blood levels of the neurotoxic Hcy. The aim of this review is to provide insight into the influence of folate status on pregnancy health outcomes, and to consider increasing evidence of a link between the extent of genome/epigenome damage and elevated risk for adverse obstetrical endpoints. Pregnant women are at risk for folate insufficiency because of the increased need for folate for rapid fetal growth, placental development and enlargement of the uterus. Inadequate folate status may cause fetal malformations, impaired fetal growth, pre-term delivery and maternal anaemia. Even some diseases of the placenta may arise from folate deficiencies. Fetal growth seems to be vulnerable to maternal folate status during the periconception period, because it has the potential to affect both the closure of the neural tube and several epigenetic mechanisms within the placenta and the fetus. Mainly on the basis of the well recognized link between maternal folate status and fetal neural tube defects, women are advised to receive folic acid supplement during the periconceptional period. Because an adequate folate supply seems to play an important role in the implantation and development of the placenta and in improving endothelial function, folic acid supplementation in the late first trimester or early second trimester might also be beneficial. PMID- 22296250 TI - Nutritional requirements during lactation. Towards European alignment of reference values: the EURRECA network. AB - There is considerable variation in reference values for micronutrient intake during lactation across Europe. The European Micronutrients Recommendations Aligned project aims to harmonize dietary recommendations throughout Europe. Recommended nutrient intakes during lactation are based on limited data and are often extrapolated from known secretion of the nutrient in milk with adjustments for bioavailability, so that differences between values can be partly ascribed to differences in methodological approaches and how these approaches were applied. Few studies have considered the impact of lactation on the mother's nutritional status. Rather, focus has been placed on the influence of maternal nutritional status on the composition of her breast milk. Most common nutritional deficits in breast milk are the result of maternal deficiencies of the water-soluble vitamins, thiamine, riboflavin and vitamins B6 and B12. Other than maternal vitamin A status, which to some extent is reflected in breast milk, concentrations of fat-soluble vitamins and most minerals in breast milk are less affected by maternal status. Factors relating to suboptimal maternal nutritional status during lactation include maternal age, diet and lifestyle factors and spacing of consecutive births. Recent research is providing new knowledge on the micronutrient requirements of lactating women. Identifying needs for research and improving understanding of the differences in values that have been derived by various committees and groups across Europe will enhance transparency and facilitate the application of dietary recommendations in policy-making decision and their translation into recommendations for lactating women. Given the wide variation in breastfeeding practices across Europe, making nutritional recommendations for lactating women is complex and challenging. Thus, it is crucial to first examine the cultural practices within and across European populations and to assess its relevance before making recommendations. PMID- 22296251 TI - The nutritional requirements of infants. Towards EU alignment of reference values: the EURRECA network. AB - This paper presents a review of the current knowledge regarding the macro- and micronutrient requirements of infants and discusses issues related to these requirements during the first year of life. The paper also reviews the current reference values used in European countries and the methodological approaches used to derive them by a sample of seven European and international authoritative committees from which background scientific reports are available. Throughout the paper, the main issues contributing to disparities in micronutrient reference values for infants are highlighted. The identification of these issues in relation to the specific physiological aspects of infants is important for informing future initiatives aimed at providing standardized approaches to overcome variability of micronutrient reference values across Europe for this age group. PMID- 22296252 TI - Physiological and public health basis for assessing micronutrient requirements in children and adolescents. The EURRECA network. AB - This paper provides an overview of the current knowledge relating to the nutritional requirements and corresponding recommended nutrient intake values of children and adolescents for micronutrients and specificities related to these requirements in the course of childhood and adolescence in Europe. Aspects that can influence micronutrient requirements, such as physiological requirements and bioavailability of the nutrients in the organism, are discussed. The methodology used to obtain the data and also the main knowledge gaps regarding these concepts are emphasized. Methodological critical points in achieving the data and physiological aspects of children and adolescents are important in order to standardize the reference values for micronutrients among Europe for these stages of life. PMID- 22296253 TI - Methodological aspects of the study of dietary patterns during pregnancy and maternal and infant health outcomes. A systematic review. AB - The objective of the present study was to systematically review the literature exploring the associations between different dietary patterns obtained from Food Frequency Questionnaires during pregnancy and the development of health-related maternal and infant outcomes in the Framework of the EURRECA Network of Excellence. A systematic search was conducted on Pubmed for literature published up to September 2009. The search strategy resulted in an initial amount of 2048 articles. After applying the selection criteria, seven studies were finally identified. Five articles were based on prospective cohort studies and the other two were case-control studies. The methods used to elaborate the dietary pattern could be classified as hypothesis-oriented (three studies) or empirically-derived (four studies). The different food frequency questionnaires used for diet assessment were self-administered, semi-quantitative and had been previously validated, but just four studies employed questionnaires validated specifically for their use in a pregnant population. The divergent methods used to assess the dietary patterns make it difficult to compare results. However, some resulting recommendations can be applied when dietary patterns during pregnancy are analyzed: to employ a validated food frequency questionnaire designed for use in pregnancy, to consider the special role exerted by mineral and vitamin supplements in this particular population group, to adequately select the time in which dietary data is collected, to adjust the results for life-style and educational characteristics, and in the case of hypothesis-oriented dietary patterns, to correctly choose the components comprising the score. PMID- 22296254 TI - Is the food frequency questionnaire suitable to assess micronutrient intake adequacy for infants, children and adolescents? AB - The objective of this study was to review how accurately micronutrient intakes in infants, children, and adolescents were assessed with validated food frequency questionnaires (FFQs) to which study quality criteria had been applied. The methodology and the analysis presented were based on several research activities carried out within the European Micronutrient Recommendation Aligned Network of Excellence. The analysis was limited to vitamin D, vitamin C, vitamin B12, folate, selenium, iron, zinc, iodine, calcium, and copper. A search strategy was defined in MEDLINE and EMBASE literature for studies validating FFQs that estimated intakes of micronutrients being evaluated. Identification of at least three validation studies per micronutrient was required to be included in the analysis. A total score for each nutrient was calculated from the mean of the correlation coefficients weighted by the quality of the study, which included a quality score that was based on sample size, statistics used, data collection procedure, consideration of seasonality and supplement use, an adjustment/weighting of the correlation coefficient according to the quality score, and a rating of the adjusted/weighted correlation. When the mean weighted correlation coefficient was equal to or higher than 0.5, micronutrient intake was considered as adequately estimated. Sufficient validation studies were identified for vitamin C, vitamin D, vitamin B12, iron, zinc, and calcium for infants and pre-school children, and vitamin C, calcium, and iron for older children and adolescents. Results showed that the FFQ was a good instrument for estimating intake of vitamin C, vitamin D, calcium, zinc and iron in infants and pre-school children, and for estimating calcium and vitamin C in children and adolescents. PMID- 22296255 TI - Diastereoselective construction of syn-1,3-dioxanes via a bismuth-mediated two component hemiacetal/oxa-conjugate addition reaction. AB - The bismuth-mediated two-component hemiacetal/oxa-conjugate addition of delta trialkylsilyloxy and delta-hydroxy alpha,beta-unsaturated aldehydes and ketones with alkyl aldehydes provides the syn-1,3-dioxanes in a highly efficient and stereoselective manner. The key advantages of this protocol are its operational simplicity and its ability to directly access electron-withdrawing groups without recourse to oxidation state adjustments. PMID- 22296256 TI - Copper-catalyzed aerobic [3+2]-annulation of N-alkenyl amidines. AB - A method for the synthesis of bi- and tricyclic amidines has been developed through copper-catalyzed aerobic [3+2]-annulation reaction of N-alkenyl amidines. These cyclic amidines could be converted into mono-benzyl-protected vicinal diamines by the reduction with aluminum hydride. PMID- 22296258 TI - Chemical composition of ambient nanoparticles on a particle-by-particle basis. AB - The nano aerosol mass spectrometer provides a quantitative measure of the elemental composition of individual, ambient nanoparticles in the 10-30 nm size range. In this work, carbon mole fraction plots are introduced as an efficient means of visualizing the full range of particle compositions in an ambient data set. These plots are constructed by plotting the composition of each particle in the data set, beginning with the particle having the highest carbon mole fraction and ending with the particle having the lowest carbon mole fraction. The method relies on the observation that the carbon content of an ambient particle is generally anticorrelated with oxygen, nitrogen, and sulfur. Carbon mole fraction plots allow internal vs external mixing of particle compositions to be assessed, and they provide a means of exploring the relationship between the oxidation of carbonaceous matter and the presence of inorganic species in a particle. It is shown that unoxidized carbonaceous matter exists primarily as externally mixed particles, whereas oxidized carbonaceous matter is found only in particles that also contain a significant amount of inorganic species. Particles containing oxidized carbonaceous matter are generally neutralized, whereas particles containing unoxidized carbonaceous matter or no carbon at all are acidic. Carbon mole fraction plots show how factor analysis methods such as the Adaptive Resonance Theory-2a algorithm (ART-2a) and positive matrix factorization partition a continuum of particle compositions into a few fixed composition profiles, and they provide a simple way to characterize how ambient particle compositions change with season and/or location. PMID- 22296259 TI - Inhibition of barnacle cyprid settlement using low frequency and intensity ultrasound. AB - Low frequency, low intensity ultrasound was demonstrated as an effective inhibitor of barnacle cyprid settlement. When the same substratum vibration amplitude (10.05 nm) and acoustic pressure (5 kPa) were applied, ultrasound at a frequency of 23 kHz significantly reduced cyprid settlement. The mechanism appeared to differ from the ultrasonic cavitation induced inhibition previously reported as no increased mortality was observed, and no change in the exploratory behaviour of cyprids was observed when they were exposed to this continuous ultrasonic irradiation regime. The application of ultrasound treatment in an intermittent mode of '5 min on and 20 min off' at 20-25 kHz and at the low intensity of 5 kPa produced the same effect as the continuous application of 23 kHz. This energy efficient approach to the use of low frequency, low intensity ultrasound may present a promising and efficient strategy regarding irradiation treatment for antifouling applications. PMID- 22296260 TI - Blaschkoid distribution of cylindromas in a germline CYLD mutation carrier. PMID- 22296261 TI - Patient satisfaction with integrated HIV and antenatal care services in rural Kenya. AB - A cluster randomized controlled trial was initiated in Kenya to determine if full integration (FI) of HIV care, including HAART, into antenatal care (ANC) clinics improves health outcomes among HIV-infected women and exposed infants, compared to a non-integrated (NI) model. This article examines ANC clients' satisfaction with and preferences regarding HIV-integrated services. In this cross-sectional study, pregnant women attending five FI clinics (n=185) and four NI clinics (n=141) completed an interviewer-administered questionnaire following an ANC visit. By self-report, 55 women (17%) were HIV(+), 230 (71%) were HIV(-), and 40 (12%) did not know their HIV status. Among HIV-infected women, 79% attending FI clinics were very satisfied with their clinic visit compared to 54% of women attending NI clinics (P=0.044); no such difference was found among HIV-uninfected women. In multivariate analysis, overall satisfaction was also independently associated with satisfaction with administrative staff, satisfaction with health care providers, positive evaluation of wait time, and having encountered a receptionist. Full integration of HIV care into antenatal clinics can significantly increase overall satisfaction with care for HIV-infected women, with no significant decrease in satisfaction for HIV-uninfected women served in the same clinics. PMID- 22296262 TI - Health-care service utilization in substance abusers receiving contingency management and standard care treatments. AB - AIM: To determine the impact of standard care and contingency management treatments on the utilization of general health-care services by substance abusers. PARTICIPANTS, DESIGN AND MEASUREMENTS: This secondary analysis pooled 1028 treatment-seeking substance abusers from five randomized clinical trials that compared the effects of standard care (SC, n = 362) to standard care plus contingency management (CM, n = 666). In each trial, subjects in the CM condition showed significantly greater reductions in substance use than their SC counterparts. For each subject, utilization of 15 general health-care services was measured 1 year prior to treatment intake and up to 9 months following treatment intake. Post-intake utilization data were pro-rated to be comparable to the 1-year pre-intake data. Paired t-tests evaluated changes in service utilization pre- and post-intake, and difference-in-differences regression models were used to estimate the impact of CM, compared to SC, on changes in the utilization of each of the 15 health services. SETTING: Out-patient community substance abuse clinics in Connecticut and Massachusetts, USA. FINDINGS: Utilization of several types of out-patient services increased significantly between the pre- and post-intake periods [e.g. dental visits (0.47, P < 0.001), community health center visits (0.50, P < 0.001), visits to a mental health professional office (1.03, P = 0.001)], while in-patient hospital care for mental health problems decreased significantly (-3.50 nights, P < 0.001). A substantial portion of these changes occurred during the treatment period. No significant differences were found between the two treatment conditions. CONCLUSIONS: Initiating out-patient substance abuse treatment is associated with changes in general health-care service utilization, independent of the type of treatment offered. PMID- 22296263 TI - Sources contributing to the average extracellular concentration of dopamine in the nucleus accumbens. AB - Mesolimbic dopamine neurons fire in both tonic and phasic modes resulting in detectable extracellular levels of dopamine in the nucleus accumbens (NAc). In the past, different techniques have targeted dopamine levels in the NAc to establish a basal concentration. In this study, we used in vivo fast scan cyclic voltammetry (FSCV) in the NAc of awake, freely moving rats. The experiments were primarily designed to capture changes in dopamine caused by phasic firing - that is, the measurement of dopamine 'transients'. These FSCV measurements revealed for the first time that spontaneous dopamine transients constitute a major component of extracellular dopamine levels in the NAc. A series of experiments were designed to probe regulation of extracellular dopamine. Lidocaine was infused into the ventral tegmental area, the site of dopamine cell bodies, to arrest neuronal firing. While there was virtually no instantaneous change in dopamine concentration, longer sampling revealed a decrease in dopamine transients and a time-averaged decrease in the extracellular level. Dopamine transporter inhibition using intravenous GBR12909 injections increased extracellular dopamine levels changing both frequency and size of dopamine transients in the NAc. To further unmask the mechanics governing extracellular dopamine levels we used intravenous injection of the vesicular monoamine transporter (VMAT2) inhibitor, tetrabenazine, to deplete dopamine storage and increase cytoplasmic dopamine in the nerve terminals. Tetrabenazine almost abolished phasic dopamine release but increased extracellular dopamine to ~500 nM, presumably by inducing reverse transport by dopamine transporter (DAT). Taken together, data presented here show that average extracellular dopamine in the NAc is low (20-30 nM) and largely arises from phasic dopamine transients. PMID- 22296264 TI - Improved serological response to H1N1 monovalent vaccine associated with viral suppression among HIV-1-infected patients during the 2009 influenza (H1N1) pandemic in the Southern Hemisphere. AB - OBJECTIVES: Patients infected with HIV-1 were targeted for vaccination against H1N1 influenza because of their anticipated increased risk of mortality associated with H1N1 infection. Reports regarding the efficacy of vaccination in HIV-1-infected patients have suggested a reduced immunogenic response compared with the general population. Hence, the study aimed to determine the serological response to pandemic H1N1 influenza vaccine in HIV-1-infected patients in a clinical setting. METHODS: A retrospective review of all HIV-1-infected patients who attended mass H1N1 vaccination between October 2009 and March 2010 at an Australian HIV clinic was carried out. Pre- and post-vaccination H1N1 antibody titres were measured. The main outcome measure was response to the vaccination, which was defined as an H1N1 antibody titre of >= 1:40 using a haemagglutination inhibition (HI) assay. RESULTS: Baseline blood samples were collected from 199 patients, of whom 154 agreed to receive vaccination; of these, 126 had pre- and post-vaccination HI titres measured. Seventy-seven of 199 patients (38.7%) showed a baseline antibody titre of >= 1:40. Eighty-five (67.4%) showed a fourfold or greater increase in titre and 109 of 126 (86.5%) achieved an antibody titre of >= 1:40 after vaccination. The serum HI H1N1 antibody geometric mean titre (GMT) for the 126 paired samples was 39.32 +/- 3.46 pre-vaccination and increased to 237.36 +/- 3.94 [standard deviation (SD)] post-vaccination (P<0.001). In a binary logistic regression analysis, HIV viral load and baseline HI antibody titre were significantly associated with post-vaccination increase in HI H1N1 antibody titre. CONCLUSIONS: A high prevalence of HI H1N1 antibodies was found before vaccination in the cohort, consistent with previous exposure to H1N1 influenza virus. The response to vaccination was considered adequate, as more than two thirds of patients achieved a fourfold or more increase in antibody titre after vaccination. The response to vaccination was significantly greater in those patients who were aviraemic for HIV, suggesting that antiretroviral therapy improves the humoral response, which is important in optimizing vaccine effectiveness. PMID- 22296265 TI - Low mortality risk but high loss to follow-up among patients in the Tanzanian national HIV care and treatment programme. AB - OBJECTIVE To analyse survival and retention rates of the Tanzanian care and treatment programme. METHODS: Routine patient-level data were available from 101 of 909 clinics. Kaplan-Meier probabilities of mortality and attrition after ART initiation were calculated. Mortality risks were corrected for biases from loss to follow-up using Egger's nomogram. Smoothed hazard rates showed mortality and attrition peaks. Cox regression identified factors associated with death and attrition. Median CD4 counts were calculated at 6 month intervals. RESULTS: In 88,875 adults, 18% were lost to follow up 12 months after treatment initiation, and 36% after 36 months. Cumulative mortality reached 10% by 12 months (15% after correcting for loss to follow-up) and 14% by 36 months. Mortality and attrition rates both peaked within the first six months, and were higher among males, those under 45 kg and those with CD4 counts below 50 cells/MUl at ART initiation. In the first year on ART, median CD4 count increased by 126 cells/MUl, with similar changes in both sexes. CONCLUSION: Earlier diagnoses through expanded HIV testing may reduce high mortality and attrition rates if combined with better patient tracing systems. Further research is needed to explore reasons for attrition. PMID- 22296266 TI - Thromboxane A2 receptor signaling facilitates tumor colonization through P selectin-mediated interaction of tumor cells with platelets and endothelial cells. AB - Thromboxane A(2) (TXA(2) ) is a prostanoid formed by thromboxane synthase using the cyclooxygenase product, prostaglandin H(2), as the substrate. TXA(2) was shown to enhance tumor metastasis, but the underlying mechanism remains unclear. B16F1 melanoma cells were intravenously injected into TXA(2) receptor (TP) knockout mice (TP(-/-) ) and wild-type littermates (WT). TP(-/-) showed a reduction in B16F1 lung colonization and mortality rate, which were associated with a decreased number of platelets. Platelet activation as assessed by P selectin expression was suppressed in TP(-/-) . A selective P-selectin neutralizing antibody decreased the lung colonization in WT mice, but not in TP( /-) . The expression of P-selectin glycoprotein ligand-1 in B16F1 and HUVEC were enhanced by treatment with U46619, a thromboxane analog. The plasma levels of vascular endothelial growth factor (VEGF) and stromal-derived factor (SDF)-1 were lower in TP(-/-) . In TP(-/-) , the mobilization of progenitor cells expressing CXCR4(+) VEGFR1(+) from bone marrow and the recruitment of those cells to lung tissues were suppressed. These results suggest that TP signaling plays a critical role in tumor colonization through P-selectin-mediated interactions between platelets-tumor cells and tumor cells-endothelial cells through the TP signaling dependent production of VEGF and SDF-1, which might be involved in the mobilization of VEGFR1(+) CXCR4(+) cells. Blockade of TP signaling might be useful in the treatment of tumor metastasis. PMID- 22296267 TI - In vitro and in vivo studies on a novel solid dispersion of repaglinide using polyvinylpyrrolidone as the carrier. AB - In order to improve the dissolution and absorption of the water insoluble drug repaglinide, a solid dispersion was developed by solvent method using polyvinylpyrrolidone K30 (PVP K30) as the hydrophilic carrier for the first time. Studies indicated that both solubility and the dissolution rate of repaglinide were significantly increased in the solid dispersion system compared with that of repaglinide raw material or physical mixtures. The repaglinide solid dispersions with PVP K30 solid state was characterized by polarizing microscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). DSC and XRD studies indicated that repaglinide existed in an amorphous form in the solid dispersion. FT-IR analysis demonstrated the presence of intermolecular hydrogen bonding between repaglinide and PVP K30 in the solid dispersion. In the in situ gastrointestinal perfusion experiment, solid dispersion was shown to remarkably enhance the absorption of repaglinide in stomach and all segments of intestine. In vivo pharmacokinetic study in rats showed that immediate and complete release of repaglinide from the solid dispersion resulted in rapid absorption that significantly increased the bioavailability and the maximum plasma concentration over repaglinide raw material. These results demonstrated PVP K30 was an appropriate carrier for solid dispersion of repaglinide, with increased dissolution and oral absorption. PMID- 22296269 TI - Uranyl peroxide oxalate cage and core-shell clusters containing 50 and 120 uranyl ions. AB - Cage clusters built from uranyl hexagonal bipyramids and oxalate ligands crystallize from slightly acidic aqueous solution under ambient conditions, facilitating structure analysis. Each cluster contains uranyl ions coordinated by peroxo ligands in a bidentate configuration. Uranyl ions are bridged by shared peroxo ligands, oxalate ligands, or through hydroxyl groups. U(50)Ox(20) contains 50 uranyl ions and 20 oxalate groups and is a topological derivative of the U(50) cage cluster that has a fullerene topology. U(120)Ox(90) contains 120 uranyl ions and 90 oxalate groups and is the largest and highest mass cluster containing uranyl ions that has been reported. It has a core-shell structure, in which the inner shell (core) consists of a cluster of 60 uranyl ions and 30 oxalate groups, identical to U(60)Ox(30), with a fullerene topology. The outer shell contains 12 identical units that each consist of five uranyl hexagonal bipyramids that are linked to form a ring (topological pentagon), with each uranyl ion also coordinated by a side-on nonbridging oxalate group. The five-membered rings of the inner and outer shells (the topological pentagons) are in correspondence and are linked through K cations. The inner shell topology has therefore templated the location of the outer shell rings, and the K counterions assume a structure directing role. Small-angle X-ray scattering data demonstrated U(50)Ox(20) remains intact in aqueous solution upon dissolution. In the case of clusters of U(120)Ox(90), the scattering data for dissolved crystals indicates the U(60)Ox(30) core persists in solution, although the outer rings of uranyl bipyramids contained in the U(120)Ox(90) core-shell cluster appear to detach from the cluster when crystals are dissolved in water. PMID- 22296268 TI - Decarbonylative approach to the synthesis of enamides from amino acids: stereoselective synthesis of the (Z)-aminovinyl-D-cysteine unit of mersacidin. AB - The Pd- and Ni-promoted decarbonylation of amino acid thioesters proceeds smoothly to yield enamides. The synthesis of the (S)-(Z)-AviMeCys subunit of mersacidin, an MRSA-active lantibiotic, via this approach, is described. PMID- 22296270 TI - Np(V) and Pu(v) ion exchange and surface-mediated reduction mechanisms on montmorillonite. AB - Due to their ubiquity and chemical reactivity, aluminosilicate clays play an important role in actinide retardation and colloid-facilitated transport in the environment. In this work, Pu(V) and Np(V) sorption to Na-montmorillonite was examined as a function of ionic strength, pH, and time. Np(V) sorption equilibrium was reached within 2 h. Sorption was relatively weak and showed a pH and ionic strength dependence. An approximate NpO(2)(+) -> Na(+) Vanselow ion exchange coefficient (Kv) was determined on the basis of Np(V) sorption in 0.01 and 1.0 M NaCl solutions at pH < 5 (Kv ~ 0.3). In contrast to Np(V), Pu(V) sorption equilibrium was not achieved on the time-scale of weeks. Pu(V) sorption was much stronger than Np(V), and sorption rates exhibited both a pH and ionic strength dependence. Differences in Np(V) and Pu(V) sorption behavior are indicative of surface-mediated transformation of Pu(V) to Pu(IV) which has been reported for a number of redox-active and redox-inactive minerals. A model of the pH and ionic strength dependence of Pu(V) sorption rates suggests that H(+) exchangeable cations facilitate Pu(V) reduction. While surface complexation may play a dominant role in Pu sorption and colloid-facilitated transport under alkaline conditions, results from this study suggest that Pu(V) ion exchange and surface-mediated reduction to Pu(IV) can immobilize Pu or enhance its colloid facilitated transport in the environment at neutral to mildly acidic pHs. PMID- 22296271 TI - Short-term exposure to tumor necrosis factor-alpha enables human osteoblasts to direct adipose tissue-derived mesenchymal stem cells into osteogenic differentiation. AB - Tumor necrosis factor-alpha (TNF-alpha) is one major inflammatory factor peaking at 24 h after bone fracture in response to injury; its role in bone healing is controversial. The aims of this study were to investigate whether the duration of exposure to TNF-alpha is crucial for the initiation of bone regeneration and to determine its underlying mechanism(s). We demonstrated that 24 h of TNF-alpha treatment significantly abrogated osteocalcin gene expression by human primary osteoblasts (HOBs). However, when TNF-alpha was withdrawn after 24 h, bone sialoprotein and osteocalcin gene expression levels in HOBs at day 7 were significantly up-regulated compared with the HOBs without TNF-alpha treatment. In contrast, continuous TNF-alpha treatment down-regulated bone sialoprotein and osteocalcin gene expression. In addition, in an indirect co-culture system, HOBs pretreated with TNF-alpha for 24 h induced significantly greater osteogenic differentiation of adipose tissue-derived mesenchymal stem cells (ASCs) than the HOBs without TNF-alpha treatment. TNF-alpha treatment also promoted endogenous bone morphogenetic protein 2 (BMP-2) production in HOBs, while blocking the BMP-2 signaling pathway with Noggin inhibited osteogenic differentiation of ASCs in the co-culture system. Furthermore, activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway after TNF-alpha treatment occurred earlier than BMP-2 protein expression. BMP-2 production by HOBs and osteogenic differentiation of ASCs in the co-culture system with HOBs was significantly decreased when HOBs were pretreated with TNF-alpha in combination with the p38 MAPK-specific inhibitor (SB203580). Taken together, we provide evidence that exposure duration is a critical element in determining TNF-alpha's effects on bone regeneration. We also demonstrate that the p38 MAPK signaling pathway regulates the expression of BMP-2 in osteoblasts, which then acts through a paracrine loop, to direct the osteoblast lineage commitment of mesenchymal stem cells. PMID- 22296272 TI - Antiallergic activity of novel isoflavone methyl-glycosides from Cordyceps militaris grown on germinated soybeans in antigen-stimulated mast cells. AB - Isoflavones are known to possess immunomodulating and antiallergic activities. Previously we identified novel isoflavone methyl-glycosides (daidzein 7-O-beta-d glucoside 4"-O-methylate (CDGM), glycitein 7-O-beta-D-glucoside 4"-O-methylate (CGLM), genistein 7-O-beta-D-glucoside 4"-O-methylate (CGNMI) and genistein 4'-O beta-D-glucoside 4"-O-methylate (CGNMII)) from Cordyceps militaris grown on germinated soybeans (GSC). The biological activity of novel isoflavone methyl glycosides, however, remains unknown. In this study, CGNMII showed the strongest inhibition of degranulation. Additionally, the release of interleukin (IL)-4 and tumor necrosis factor (TNF)-alpha was decreased by CGNMII in antigen-stimulated RBL-2H3 cells. To elucidate the antiallergic mechanism of CGNMII, we examined whether it affected levels of signaling molecules responsible for degranulation. The levels of activated Lyn, Syk, PLCgamma1 and LAT proteins were reduced in CGNMII treated RBL-2H3 cells. CGNMII also inhibited the activation of AKT and ERK1/2 proteins. These results suggest that CGNMII might be used as a therapeutic agent for allergic diseases. PMID- 22296274 TI - Two tyrosyl radicals stabilize high oxidation states in cytochrome C oxidase for efficient energy conservation and proton translocation. AB - The reaction of oxidized bovine cytochrome c oxidase (bCcO) with hydrogen peroxide (H(2)O(2)) was studied by electron paramagnetic resonance (EPR) to determine the properties of radical intermediates. Two distinct radicals with widths of 12 and 46 G are directly observed by X-band EPR in the reaction of bCcO with H(2)O(2) at pH 6 and pH 8. High-frequency EPR (D-band) provides assignments to tyrosine for both radicals based on well-resolved g-tensors. The wide radical (46 G) exhibits g-values similar to a radical generated on L-Tyr by UV irradiation and to tyrosyl radicals identified in many other enzyme systems. In contrast, the g-values of the narrow radical (12 G) deviate from L-Tyr in a trend akin to the radicals on tyrosines with substitutions at the ortho position. X band EPR demonstrates that the two tyrosyl radicals differ in the orientation of their beta-methylene protons. The 12 G wide radical has minimal hyperfine structure and can be fit using parameters unique to the post-translationally modified Y244 in bCcO. The 46 G wide radical has extensive hyperfine structure and can be fit with parameters consistent with Y129. The results are supported by mixed quantum mechanics and molecular mechanics calculations. In addition to providing spectroscopic evidence of a radical formed on the post-translationally modified tyrosine in CcO, this study resolves the much debated controversy of whether the wide radical seen at low pH in the bovine enzyme is a tyrosine or tryptophan. The possible role of radical formation and migration in proton translocation is discussed. PMID- 22296275 TI - Cancer-associated fibroblasts and CD163-positive macrophages in oral squamous cell carcinoma: their clinicopathological and prognostic significance. AB - BACKGROUND: Stromal cells are believed to affect cancer invasion and metastasis. The purpose of this study was to evaluate the distribution of cancer-associated fibroblasts (CAFs) and the incidence of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC), focusing on clinicopathological factors and patient prognosis, as well as cancer invasion. METHODS: The study included 108 patients with OSCC. Anti-alpha-smooth muscle actin, CD68, and CD163 antibodies were used to identify CAFs and TAMs. CAFs were divided into 4 grades on the basis of staining intensity: negative (0), scanty (1), focal (2), and abundant (3). The most intensive areas of macrophage concentration in each tumor invasive stroma were also evaluated. RESULTS: The cancer specimens were divided into Grade 0/1, Grade 2, and Grade 3 on the basis of CAF grade. In addition, they were divided into low- and high-grade groups on the basis of the number of CD68-positive and CD163-positive macrophages. The latter were significantly increased in the Grade 2 CAF group compared to the Grade 0/1 group (P = 0.009). Kaplan-Meier and multivariate survival analyses revealed that Grade 2 CAFs (P = 0.003) and high CD163-positive macrophage levels (P = 0.007) significantly correlated with a poor outcome in patients with OSCC, and that a high CD163-positive macrophage level was a significant and an independent prognostic factor (P = 0.045). CONCLUSIONS: Cancer-associated fibroblasts and CD163-positive macrophages may be potential prognostic predictors of OSCC. PMID- 22296276 TI - An analysis of five clear cell papillary cystadenomas of mesosalpinx and broad ligament: four associated with von Hippel-Lindau disease and one aggressive sporadic type. AB - AIMS: Clear cell papillary cystadenoma (CCPC) is associated with von Hippel Lindau disease (VHLD), but rarely involves mesosalpinx and broad ligament (M/BL). This study provides new data about its behaviour and immunophenotype. METHODS AND RESULTS: We performed an analysis of four benign cases of CCPC of M/BL with either characteristic clinical features or genetic markers [loss of heterozygosity (LOH)] of VHLD in patients ranging from 24 to 36 years and a sporadic case in a 52-year-old presenting with peritoneal metastases. All CCPCs were papillary but had solid and tubular areas. Haemorrhage, thrombosis and scarring were constant features and related to an unusual pattern of sub epithelial vascularity. All clear or oxyphilic cells co-expressed cytokeratin 7 (CK7), CAM5.2 and vimentin, with strong apical CD10 and nuclear paired box gene 2 (PAX2) immunoreactivity. Three cases also showed positivity for VHL40, epithelial membrane antigen (EMA), Wilms' tumour suppressor gene (WT-1) and cancer antigen 125 (CA125) but only one expressed renal cell carcinoma (RCC) antigen. Vascular plexus overexpressed nuclear and cytoplasmic WT-1. CONCLUSION: The VHLD associated cases appeared to be benign, but the sporadic case exhibited a low malignant potential. CCPCs show histological and immunophenotypical similarities with the recently reported clear cell papillary RCC, although the previously unreported apical CD10 and nuclear PAX2 expression may be related to their mesonephric origin. CCPC has a distinctive sub-epithelial vascular pattern that is consistent with its pathogenesis. PMID- 22296277 TI - Comparison of interleukin-6 levels in maternal and umbilical cord blood in early- and late-onset preeclampsia. AB - PURPOSE: Increased inflammatory response and cytokines are claimed to play a significant role in the etiology of preeclampsia. Interleukin-6 (IL-6) is a proinflammatory cytokine. Limited number of studies evaluating IL-6 levels in preeclamptic patients have produced conflicting results. Therefore, the present study sought to compare maternal and umbilical cord serum levels of IL-6 in early and late-onset preeclamptic pregnancies as well as in normal pregnancies. MATERIALS AND METHODS: A total of 69 participants were enrolled in the study. The control group consisted of 24 participants with normal pregnancies. Preeclampsia group consisted of 45 participants. The preeclampsia group was further classified into the subgroups of early- and late-onset preeclampsia. Late-onset preeclampsia group consisted of 24 women whereas early-onset preeclampsia group consisted of 21 women. Serum and umbilical cord samples of IL-6 were compared. RESULTS: There was no significant difference between maternal and umbilical cord serum IL-6 concentrations between the preeclampsia and control group. No significant difference was observed in maternal and umbilical cord serum IL-6 levels between early- and late-onset preeclampsia groups. CONCLUSION: Our results do not support an increase in IL-6 levels in patients with early- and late-onset preeclampsia. The clinical relevance of our findings needs to be further investigated. PMID- 22296278 TI - Emotional time distortions: the fundamental role of arousal. AB - An emotion-based lengthening effect on the perception of durations of emotional pictures has been assumed to result from an arousal-based mechanism, involving the activation of an internal clock system. The aim of this study was to systematically examine the arousal effect on time perception when different discrete emotions were considered. The participants were asked to verbally estimate the duration of emotional pictures from the International Affective Picture System (IAPS). The pictures varied either in arousal level, i.e., high/low-arousal, for the same discrete emotion (disgust or sadness) or in the depicted emotion, e.g., disgust/fear for pictures matched for arousal (high arousal). The results systematically revealed a lengthening effect on the perception of the duration of the emotional compared to the neutral pictures and indicated that the magnitude of this effect increased with arousal level. Nevertheless, variations in time perception were observed for one and the same arousal level, with the duration of disgust-inducing pictures (e.g., body mutilation) being judged longer than that of fear-inducing pictures (e.g., snake). These results suggest that arousal is a fundamental mechanism mediating the effect of emotion on time perception. However, the effect cannot be reduced to arousal, since the impact of the content of pictures also plays a critical role. PMID- 22296279 TI - Synthesis, basicity, structural characterization, and biochemical properties of two [(3-hydroxy-4-pyron-2-yl)methyl]amine derivatives showing antineoplastic features. AB - The N,N'-bis[(3-hydroxy-4-pyron-2-yl)methyl]-N,N'-dimethylethylendiamine (malten) and 4,10-bis[(3-hydroxy-4-pyron-2-yl)methyl]-1,7-dimethyl-1,4,7,10 tetraazacyclododecane (maltonis) were synthesized and characterized. The acid base behavior, structural characterizations, and biochemical studies in aqueous solution were reported. Each compound contains two 3-hydroxy-2-methyl-4-pyrone units (maltol) symmetrically spaced by a polyamine fragment, the 1,4 dimethylethylendiamine (malten), or the 1,7-dimethyl-1,4,7,10 tetraazacyclododecane (maltonis). They are present at physiological pH 7.4 in the form of differently charged species: neutral but in a zwitterion form for malten and monopositive with an internal separation of charges for maltonis. Malten and maltonis are both able to alter the chromatin structure inducing the covalent binding of genomic DNA with proteins, a feature consistent with the known antiproliferative activity exerted by this class of molecules. Solid-state results and MD simulations in water show that malten, because of its molecular topology, should be more prone than maltonis to act as a donor of H-bonds in intermolecular contacts, thus it should give a better noncovalent approach with the negatively charged DNA. Crystal structures of [H(2)malten](2+) and [H(2)maltonis](2+) cations were also reported. PMID- 22296280 TI - Preferences for evidence-based practice dissemination in addiction agencies serving women: a discrete-choice conjoint experiment. AB - AIM: To model variables influencing the dissemination of evidence-based practices to addiction service providers and administrators. DESIGN: A discrete choice conjoint experiment. We systematically varied combinations of 16 dissemination variables that might influence the adoption of evidence-based practices. Participants chose between sets of variables. SETTING: Canadian agencies (n = 333) providing addiction services to women. PARTICIPANTS: Service providers and administrators (n = 1379). MEASUREMENTS: We estimated the relative importance and optimal level of each dissemination variable. We used latent class analysis to identify subsets of participants with different preferences and simulated the conditions under which participants would use more demanding professional development options. FINDINGS: Three subsets of participants were identified: outcome-sensitive (52%), process-sensitive (29.6%) and demand-sensitive (18.2%). Across all participants, the number of clients who were expected to benefit from an evidence-based practice exerted the most influence on dissemination choices. If a practice was seen as feasible, co-worker and administrative support influenced decisions. Client benefits were most important to outcome-sensitive participants; type of dissemination process (e.g. active versus passive learning) was more important to process-sensitive participants. Brief options with little follow-up were preferred by demand sensitive participants. Simulations predicted that initiatives selected and endorsed by government funders would reduce participation. CONCLUSIONS: Clinicians and administrators are more likely to adopt evidence-based addiction practices if the practice is seen as helpful to clients, and if it is supported by co-workers and program administration. PMID- 22296281 TI - Abscisic acid mediates the formation of a suberized stem scar tissue in tomato fruits. AB - During harvest, fleshy berry tomato fruits (Solanum lycopersicum) were wounded at their stem scar. Within 3 d, this wound was rapidly sealed by a process covering the wound site with a membranous layer which effectively protects the tomato fruit from excessive water loss, nutrient elution and the entry of pathogens. Chemical analysis of the de novo synthesized stem scar tissue revealed the presence of aromatic and aliphatic components characteristic of the biopolyester suberin. Gene expression patterns associated with suberization were identified at the stem scar region. Changes in the relative abundance of different transcripts suggested a potential involvement of the plant hormone abscisic acid (ABA) in the wound-healing processes. The amount of ABA present in the stem scar tissue showed a significantly increased level during wound healing, whereas ABA-deficient mutants notabilis, flacca and sitiens were largely devoid of this rise in ABA levels. The mutant fruits showed a retarded and less efficient suberization response at the stem scar wound, whereas the rate and strength of this response were positively correlated with ABA content. These results clearly indicate in vivo the involvement of ABA in the suberization-based wound-healing processes at the stem scar tissue of tomato fruits. PMID- 22296282 TI - Bovine serum albumin adsorption to iron-oxide coated sands can change microsphere deposition mechanisms. AB - Particulate colloids often occur together with proteins in sewage-impacted water. Using Bovine Serum Albumin (BSA) as a surrogate for protein in sewage, column experiments investigating the capacity of iron-oxide coated sands to remove latex microspheres from water revealed that microsphere attenuation mechanisms depended on antecedent BSA coverage. Dual pulse experiment (DPE) results suggested that where all BSA was adsorbed, subsequent multiple pore volume microsphere breakthrough curves reflected progressively reduced colloid deposition rates with increasing adsorbed BSA content. Modeling colloid responses suggested adsorption of 1 MUg BSA generated the same response as blockage by between 7.1 * 10(8) and 2.3 * 10(9) deposited microspheres. By contrast, microsphere responses in DPEs where BSA coverage of the deposition sites approached/reached saturation revealed the coated sand maintained a finite capacity to attenuate microspheres, even when incapable of further BSA adsorption. Subsequent microsphere breakthrough curves demonstrated the matrix's colloid attenuation capacity progressively increased with continued microsphere deposition. Experimental findings suggested BSA adsorption on the sand surface approaching/reaching saturation generated attractive deposition sites for colloids, which became progressively more attractive with further colloid deposition (filter ripening). Results demonstrate that adsorption of a single type of protein may either enhance or inhibit colloid mobility in saturated porous media. PMID- 22296283 TI - Atrial fibrillation ablation using a closed irrigation radiofrequency ablation catheter. AB - BACKGROUND: Catheter ablation is an effective therapy for symptomatic, medically refractory atrial fibrillation (AF). Open-irrigated radiofrequency (RF) ablation catheters produce transmural lesions at the cost of increased fluid delivery. In vivo models suggest closed-irrigated RF catheters create equivalent lesions, but clinical outcomes are limited. METHODS: A cohort of 195 sequential patients with symptomatic AF underwent stepwise AF ablation (AFA) using a closed-irrigation ablation catheter. Recurrence of AF was monitored and outcomes were evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models. RESULTS: Mean age was 59.0 years, 74.9% were male, 56.4% of patients were paroxysmal and mean duration of AF was 5.4 years. Patients had multiple comorbidities including hypertension (76.4%), tobacco abuse (42.1%), diabetes (17.4%), and obesity (mean body mass index 30.8). The median follow-up was 55.8 weeks. Overall event-free survival was 73.6% with one ablation and 77.4% after reablation (reablation rate was 8.7%). Median time to recurrence was 26.9 weeks. AF was more likely to recur in patients being treated with antiarrhythmic therapy at the time of last follow-up (recurrence rate 30.3% with antiarrhythmic drugs, 13.2% without antiarrhythmic drugs; hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.1-4.4, P = 0.024) and in those with a history of AF greater than 2 years duration (HR 2.7, 95% CI 1.1-6.9, P = 0.038). CONCLUSIONS: Our study represents the largest cohort of patients receiving AFA with closed-irrigation ablation catheters. We demonstrate comparable outcomes to those previously reported in studies of open-irrigation ablation catheters. Given the theoretical benefits of a closed-irrigation system, a large head-to-head comparison using this catheter is warranted. PMID- 22296284 TI - Fractional laser resurfacing for acne scars: a review. AB - This review investigates the effectiveness of ablative and nonablative fractional photothermolysis (FP) lasers for treating facial acne scars. Twenty-six studies (13 ablative FP, 13 nonablative FP) published between 2003 and January 2011 were reviewed. Quantitative and qualitative data from each article were examined and analysed. Four studies were split-face randomized controlled studies. While the data analysed were all clinically relevant and significant, there were some methodological differences between the studies. Outcomes included subjective and objective assessment of scar appearance, pre- and postoperative treatment, side effects and pain scores. A small number of studies used three-dimensional optical imaging profiling and histology for objective assessment. Even allowing for methodological variability, ablative FP had an improvement range of 26-83% whereas nonablative FP had an improvement range of 26-50%. Patients who underwent treatment with an ablative FP laser experienced erythema for 3-14 days which resolved by 12 weeks, whereas patients who opted for the nonablative FP laser experienced erythema for between 1 and 3 days and this resolved within a week. A higher proportion of patients (up to 92.3%) who underwent ablative FP experienced postinflammatory hyperpigmentation (PIH) than those who had nonablative FP (up to 13%). The maximum duration of PIH in ablative FP was up to 6 months whereas in nonablative FP it lasted for up to 1 week. The procedure with ablative FP was relatively uncomfortable compared with nonablative FP. The pain score with ablative FP ranged from 5.90 to 8.10 (scale 1-10) and with nonablative FP from 3.90 to 5.66 (scale 1-10). PMID- 22296285 TI - Kinetics and thermodynamics of chlorpromazine interaction with lipid bilayers: effect of charge and cholesterol. AB - Passive transport across cell membranes is the major route for the permeation of xenobiotics through tight endothelia such as the blood-brain barrier. The rate of passive permeation through lipid bilayers for a given drug is therefore a critical step in the prediction of its pharmacodynamics. We describe a detailed study on the kinetics and thermodynamics for the interaction of chlorpromazine (CPZ), an antipsychotic drug used in the treatment of schizophrenia, with neutral and negatively charged lipid bilayers. Isothermal titration calorimetry was used to study the partition and translocation of CPZ in lipid membranes composed of pure POPC, POPC:POPS (9:1), and POPC:Chol:POPS (6:3:1). The membrane charge due to the presence of POPS as well as the additional charge resulting from the introduction of CPZ in the membrane were taken into account, allowing the calculation of the intrinsic partition coefficients (K(P)) and the enthalpy change (DeltaH) associated with the process. The enthalpy change upon partition to all lipid bilayers studied is negative, but a significant entropy contribution was also observed for partition to the neutral membrane. Because of the positive charge of CPZ, the presence of negatively charged lipids in the bilayer increases both the observed amount of CPZ that partitions to the membrane (KP(obs)) and the magnitude of DeltaH. However, when the electrostatic effects are discounted, the intrinsic partition coefficient was smaller, indicating that the hydrophobic contribution was less significant for the negatively charged membrane. The presence of cholesterol strongly decreases the affinity of CPZ for the bilayer in terms of both the amount of CPZ that associates with the membrane and the interaction enthalpy. A quantitative characterization of the rate of CPZ translocation through membranes composed of pure POPC and POPC:POPS (9:1) was also performed using an innovative methodology developed in this work based on the kinetics of the heat evolved due to the interaction of CPZ with the membranes. PMID- 22296288 TI - Volunteering predicts happiness among older Maori and non-Maori in the New Zealand health, work, and retirement longitudinal study. AB - OBJECTIVES: This study sought to understand the relationship between volunteer activity and happiness among a sample of older adult New Zealanders. It specifically sought to determine if ethnicity (Maori vs. non-Maori) and economic living standards (ELS) functioned as moderators of the relationship between volunteering and happiness. METHOD: Data were garnered from the 2008 administration of the New Zealand Health, Work, and Retirement Longitudinal Study. Correlational and multiple regression procedures were employed to examine study hypotheses. RESULTS: Results from multiple regression analyses showed that the amount of volunteering per week was a unique predictor of the overall level of happiness. Moderation analyses indicated that ethnicity did not function as a moderator of the relationship between volunteering and happiness, but ELS did. Those with low ELS evidenced a stronger relationship between volunteering and happiness than those with high ELS. Results also indicated that Maori and those with low ELS volunteered more frequently than non-Maori and those with high ELS. CONCLUSION: This study provides evidence that volunteering is related to increased happiness, irrespective of ethnicity. It also provides further evidence that the relationship between volunteering and happiness is moderated by economic resources. Older individuals at the low end of the economic spectrum are likely to benefit more from volunteering than those at the high end. PMID- 22296289 TI - 'I can't see any reason for stopping doing anything, but I might have to do it differently'--restoring hope to patients with persistent non-specific low back pain--a qualitative study. AB - PURPOSE: To explore the differences in narrative between patients with persistent non-specific low back pain (PLBP) who benefited from a pain management programme, and those who did not benefit. METHOD: We conducted interviews with 20 patients attending a pain management programme; prior to attending the programme, immediately following the programme and at one year. Our analysis focused on a theoretical sample of patients who either described dramatic life improvements at one year, and who described themselves as much worse. We used the methods of grounded theory. RESULTS: We found that finding hope was central to good outcome. Patients restored hope by making certain changes; (a) deconstructing specific fears, (b) constructing an acceptable explanatory model (c) reconstructing self identity by making acceptable changes. Those who had not restored hope retained fears of loss of self, remained committed to the biomedical model and were unable to make acceptable changes. CONCLUSIONS: Our findings may help to operationalise the restoration of hope in patients with PLBP. Firstly, health care professionals need to identify and resolve any specific fears of movement. Secondly, patients need an acceptable explanatory model that fits their experience and personal narrative. Finally our study confirms the centrality of self concept to recovery. PMID- 22296290 TI - Effect of water during the quantitation of formate in photocatalytic studies on CO2 reduction in dimethylformamide. AB - The effect of the water concentration on the quantitation of formate from dimethylformamide in the presence of electron-donating bases using ion chromatography is reported. This observation has important implications in the area of the photocatalytic reduction of CO(2), where formate levels are often used to calculate catalyst turnover numbers. PMID- 22296291 TI - Iron(III) modification of Bacillus subtilis membranes provides record sorption capacity for arsenic and endows unusual selectivity for As(V). AB - Bacillus subtilis is a spore forming bacterium that takes up both inorganic As(III) and As(V). Incubating the bacteria with Fe(III) causes iron uptake (up to ~0.5% w/w), and some of the iron attaches to the cell membrane as hydrous ferric oxide (HFO) with additional HFO as a separate phase. Remarkably, 30% of the Bacillus subtilis cells remain viable after treatment by 8 mM Fe(III). At pH 3, upon metalation, As(III) binding capacity becomes ~0, while that for As(V) increases more than three times, offering an unusual high selectivity for As(V) against As(III). At pH 10 both arsenic forms are sorbed, the As(V) sorption capacity of the ferrated Bacillus subtilis is at least of 11 times higher than that of the native bacteria. At pH 8 (close to pH of most natural water), the arsenic binding capacity per mole iron for the ferrated bacteria is greater than those reported for any iron containing sorbent. A sensitive arsenic speciation approach is thus developed based on the binding of inorganic arsenic species by the ferrated bacteria and its unusual high selectivity toward As(V) at low pH. PMID- 22296292 TI - Communicating health decisions: an analysis of messages posted to online prostate cancer forums. AB - BACKGROUND: Experiential websites such as message forums and blogs allow Prostate Cancer (PCa) patients to communicate their health decisions to peers. The issues surrounding this form of indirect involvement in public health are little understood. OBJECTIVE: This paper explores the types of decision-making processes that people are exposed to on PCa online message boards. The kinds of treatment choices patients are making and the reports of their decision-making processes to peers through an online environment are examined in the context of the Heuristic Systematic Model. METHOD: Messages about treatment decision making were collected from four PCa websites. In total, 137 messages were selected from blogs and online forums and their decision-making processes coded. RESULTS: Men looking online for information about treatment options for PCa are exposed to a range of decision-making processes. Just under half (49.6%) of the messages reported non systematic decision processes, with deferral to the doctor and proof of cancer removal being the most common. For systematic processing (36.5%), messages most commonly considered treatment outcomes and side-effects. Processes did not vary between the blogs and online forums. DISCUSSION AND CONCLUSION: Compared to previous studies far fewer messages reported non-systematic decision processes and only a small number of messages reflected lay beliefs or misbeliefs about PCa treatment. Implications for men and their clinicians of seeking health information online are discussed. PMID- 22296293 TI - Cytotoxicity of benzyl isothiocyanate in normal renal proximal tubular cells and its modulation by glutathione. AB - In the present study, we examined the toxicity of benzyl ITC (BITC) and its urinary mercapturic acid metabolite (BITC-NAC), using a normal renal proximal tubular cell line, pig LLC-PK1. BITC increased cell death with an IC(50) value of about 7 MUM, whereas the cytotoxic effect of BITC-NAC was five times weaker than that of BITC. We observed a significant necrosis of the compounds on LLC-PK1 cells with oxidative stress. In the presence of 5 mM glutathione (GSH), comparable to physiological levels, the cytotoxicity of BITC-NAC as well as BITC was significantly reduced. Furthermore, the increase in intracellular GSH levels by pretreatment with NAC before the BITC treatment resulted in inhibition of the BITC-induced necrotic events as well as intracellular oxidative stress. These results suggest that GSH is a determinant of cellular resistance against the BITC mediated and oxidative stress-dependent cytotoxicity in renal proximal tubular cells. PMID- 22296294 TI - Role of Lactobacillus acidophilus loaded floating beads in chronic fatigue syndrome: behavioral and biochemical evidences. AB - BACKGROUND: In recent years the interface between neuropsychiatry and gastroenterology has converged in to a new discipline referred to as enteric neuroscience. Implications of brain-gut communication in the pathogenesis of psychiatric disorders indicate a possible role of suitably packaged/delivered probiotics as newer therapeutic options. In the present study probable role of per-oral administration of free Lactobacillus acidophilus (LAB) and LAB loaded alginate beads in attenuation of the symptoms associated with chronic fatigue syndrome (CFS) were evaluated. METHODS: Chronic fatigue syndrome following physical fatigue was induced in rats by forcing them to swim (forced swim test; FST) in water till exhaustion, after weighing them down with 10% their body weight, daily for 28 days. Immobility (I) and postswim fatigue time (PSF) were taken as suitable markers. Free LAB and LAB loaded floating beads (FBs) were administered, from 21 to 28 days. KEY RESULTS: Immobility and PSF were found to increase considerably in FST rats (665 +/- 22 s and 196 +/- 6 s) as compared with the naive (32 +/- 7 s and 22 +/- 2 s) at 20 days, establishing severe fatigue like behavior. FST control group exhibited significant (P < 0.05) hypertrophy of spleen, hypotrophy of thymus, and increased oxido-nitrosative stress in brain and tumor necrosis factor-alpha (TNF-alpha) levels in serum. Treatment with LAB and LAB FBs significantly decreased I and PSF and attenuated (P < 0.05) oxido nitrosative stress and TNF-alpha levels. Spleen and thymus were also restored to their original size in this group. CONCLUSIONS & INFERENCES: The findings suggest a valuable therapeutic role of LAB especially when incorporated into alginate beads for the treatment of CFS. PMID- 22296295 TI - Synthesis of the AviMeCys-containing D-ring of mersacidin. AB - A chemical synthesis of the D-ring of mersacidin is reported. The synthetic route relied upon development of a method for late-stage introduction of an unusual S [(Z)-2-aminovinyl]-(3S)-3-methyl-D-cysteine (AviMeCys) functional group via an oxidative decarbonylation/decarboxylation reaction. PMID- 22296296 TI - Domain swapping proceeds via complete unfolding: a 19F- and 1H-NMR study of the Cyanovirin-N protein. AB - Domain swapping creates protein oligomers by exchange of structural units between identical monomers. At present, no unifying molecular mechanism of domain swapping has emerged. Here we used the protein Cyanovirin-N (CV-N) and (19)F-NMR to investigate the process of domain swapping. CV-N is an HIV inactivating protein that can exist as a monomer or a domain-swapped dimer. We measured thermodynamic and kinetic parameters of the conversion process and determined the size of the energy barrier between the two species. The barrier is very large and of similar magnitude to that for equilibrium unfolding of the protein. Therefore, for CV-N, overall unfolding of the polypeptide is required for domain swapping. PMID- 22296297 TI - Low free testosterone in HIV-infected men is not associated with subclinical cardiovascular disease. AB - OBJECTIVES: Low testosterone (T) is associated with cardiovascular disease (CVD) and increased mortality in the general population; however, the impact of T on subclinical CVD in HIV disease is unknown. This study examined the relationships among free testosterone (FT), subclinical CVD, and HIV disease. METHODS: This was a cross-sectional analysis in 322 HIV-uninfected and 534 HIV-infected men in the Multicenter AIDS Cohort Study. Main outcomes were coronary artery calcification presence, defined as a coronary artery calcium (CAC) score >10 (CAC score was the geometric mean of the Agatston scores of two computed tomography replicates), and far wall common carotid intima-media thickness (IMT)/carotid lesion presence by B-mode ultrasound. RESULTS: Compared with the HIV-uninfected men in our sample, HIV-infected men were younger, with lower body mass index (BMI) and more often Black. HIV-infected men had lower FT (age-adjusted FT 88.7 ng/dL vs. 101.7 ng/dL in HIV-uninfected men; P=0.0004); however, FT was not associated with CAC, log carotid IMT, or the presence of carotid lesions. HIV status was not associated with CAC presence or log carotid IMT, but was associated with carotid lesion presence (adjusted odds ratio 1.69; 95% confidence interval 1.06, 2.71) in HIV-infected men compared with HIV-uninfected men. CONCLUSIONS: Compared with HIV uninfected men, HIV-infected men had lower FT, as well as more prevalent carotid lesions. In both groups, FT was not associated with CAC presence, log carotid IMT, or carotid lesion presence, suggesting that FT does not influence subclinical CVD in this population of men with and at risk for HIV infection. PMID- 22296299 TI - Mimicking conjugated polymer thin-film photophysics with a well-defined triblock copolymer in solution. AB - Conjugated polymers (CPs) are promising materials for use in electronic applications, such as low-cost, easily processed organic photovoltaic (OPV) devices. Improving OPV efficiencies is hindered by a lack of a fundamental understanding of the photophysics in CP-based thin films that is complicated by their heterogeneous nanoscale morphologies. Here, we report on a poly(3 hexylthiophene)-block-poly(tert-butyl acrylate)-block-poly(3-hexylthiophene) rod coil-rod triblock copolymer. In good solvents, this polymer resembles solutions of P3HT; however, upon the addition of a poor solvent, the two P3HT chains within the triblock copolymer collapse, affording a material with electronic spectra identical to those of a thin film of P3HT. Using this new system as a model for thin films of P3HT, we can attribute the low fluorescence quantum yield of films to the presence of a charge-transfer state, providing fundamental insights into the condensed phase photophysics that will help to guide the development of the next generation of materials for OPVs. PMID- 22296301 TI - Increased levels of deleted in malignant brain tumours 1 (DMBT1) in active bacteria-related appendicitis. AB - AIMS: Deleted in malignant brain tumours 1 (DMBT1; gp340) is a secreted glycoprotein which is found in the surface lining epithelia of human small and large intestine. DMBT1 is suggested to play a role in enterocyte differentiation and surface protection from intestinal bacteria. The aim of this study was to elucidate DMBT1 expression in bacteria-related active intestinal inflammation such as appendicitis. METHODS AND RESULTS: mRNA and protein levels of DMBT1 were analysed in surgical resections of 50 appendices (active inflammation: n = 25). In non-actively inflamed appendices, inter-individual differences in basal DMBT1 levels of enterocytes and some non-epithelial cells were found. In active appendicitis, enterocytic DMBT1 mRNA expression was increased approximately fivefold, which was paralleled by a corresponding increase of cytoplasmic and secreted DMBT1 protein levels. Increased DMBT1 expression was predominant in enterocytes adjacent to erosive lesions or ulcers. CONCLUSIONS: Our data demonstrate that bacteria-related active inflammation results in a sharp increase of DMBT1 levels in enterocytes. These findings substantiate the view that DMBT1 is of functional relevance for host defence and modulation of the course of intestinal bacteria-related inflammatory responses. PMID- 22296302 TI - Intraparticle reduction of arsenite (As(III)) by nanoscale zerovalent iron (nZVI) investigated with In Situ X-ray absorption spectroscopy. AB - While a high efficiency of contaminant removal by nanoscale zerovalent iron (nZVI) has often been reported for several contaminants of great concern, including aqueous arsenic species, the transformations and translocation of contaminants at and within the nanoparticles are not clearly understood. By analysis using in situ time-dependent X-ray absorption spectroscopy (XAS) of the arsenic core level for nZVI in anoxic As(III) solutions, we have observed that As(III) species underwent two stages of transformation upon adsorption at the nZVI surface. The first stage corresponds to breaking of As-O bonds at the particle surface, and the second stage involves further reduction and diffusion of arsenic across the thin oxide layer enclosing the nanoparticles, which results in arsenic forming an intermetallic phase with the Fe(0) core. Extended X-ray absorption fine-structure (EXAFS) data from experiments conducted at different iron/arsenic ratios indicate that the reduced arsenic species tend to be enriched at the surface of the Fe(0) core region and had limited mobility into the interior of the metal core within the experimental time frame (up to 22 h). Therefore, there was an accumulation of partially reduced arsenic at the Fe(0)/oxide interface when a relatively large arsenic content was present in the solid phase. These results illuminate the role of intraparticle diffusion and reduction in affecting the chemical state and spatial distribution of arsenic in nZVI materials. PMID- 22296303 TI - Expression of a bacterial feedback-insensitive 3-deoxy-D-arabino-heptulosonate 7 phosphate synthase of the shikimate pathway in Arabidopsis elucidates potential metabolic bottlenecks between primary and secondary metabolism. AB - The shikimate pathway of plants mediates the conversion of primary carbon metabolites via chorismate into the three aromatic amino acids and to numerous secondary metabolites derived from them. However, the regulation of the shikimate pathway is still far from being understood. We hypothesized that 3-deoxy-d arabino-heptulosonate 7-phosphate synthase (DAHPS) is a key enzyme regulating flux through the shikimate pathway. To test this hypothesis, we expressed a mutant bacterial AroG gene encoding a feedback-insensitive DAHPS in transgenic Arabidopsis plants. The plants were subjected to detailed analysis of primary metabolism, using GC-MS, as well as secondary metabolism, using LC-MS. Our results exposed a major effect of bacterial AroG expression on the levels of shikimate intermediate metabolites, phenylalanine, tryptophan and broad classes of secondary metabolite, such as phenylpropanoids, glucosinolates, auxin and other hormone conjugates. We propose that DAHPS is a key regulatory enzyme of the shikimate pathway. Moreover, our results shed light on additional potential metabolic bottlenecks bridging plant primary and secondary metabolism. PMID- 22296304 TI - Risk factors affecting Tests of Infant Motor Performance (TIMP) in pre-term infants at post-conceptional age of 40 weeks. AB - OBJECTIVE: The purpose of this study is to correlate clinical factors with the Test of Infant Motor Performance (TIMP) in pre-term infants at a post conceptional age of 40 weeks. METHODS: The study enrolled 80 pre-term infants admitted to the Neonatal Intensive Care Unit (NICU). Data on birth weight, multiple birth, sex, delivery type, Apgar scores at 1 minute and 5 minutes, neonatal seizures and Intraventricular Haemorrhage (IVH) as assessed by echoencephalography were retrospectively analysed through a review of relevant medical records. RESULTS: IVH was the clinical factor most strongly correlated with the TIMP scores. Other clinical factors which significantly affected the TIMP scores were caesarean section, neonatal seizures, low birth weight and multiple births. CONCLUSIONS: When pre-term infants exhibit risk factors of developmental delay, it is suggestd that TIMP is performed early in life among pre-term infants and the results can be used to select infants for early interventions. PMID- 22296305 TI - Activated ribonucleotides undergo a sugar pucker switch upon binding to a single stranded RNA template. AB - Template-directed polymerization of chemically activated ribonucleotide monomers, such as nucleotide 5'-phosphorimidazolides, has been studied as a model for nonenzymatic RNA replication during the origin of life. Kinetic studies of the polymerization of various nucleotide monomers on oligonucleotide templates have suggested that the A-form (C3'-endo sugar pucker) conformation is optimal for both monomers and templates for efficient copying. However, RNA monomers are predominantly in the C2'-endo conformation when free in solution, except for cytidine, which is approximately equally distributed between the C2'-endo and C3' endo conformations. We hypothesized that ribonucleotides undergo a switch in sugar pucker upon binding to an A-type template and that this conformational switch allows or enhances subsequent polymerization. We used transferred nuclear Overhauser effect spectroscopy (TrNOESY), which can be used for specific detection of the bound conformation of small-molecule ligands with relatively weak affinity to receptors, to study the interactions between nucleotide 5' phosphorimidazolides and single-stranded oligonucleotide templates. We found that the sugar pucker of activated ribonucleotides switches from C2'-endo in the free state to C3'-endo upon binding to an RNA template. This switch occurs only on RNA and not on DNA templates. Furthermore, activated 2'-deoxyribonucleotides maintain a C2'-endo sugar pucker in both the free and template-bound states. Our results provide a structural explanation for the observations that activated ribonucleotides are superior to activated deoxyribonucleotides and that RNA templates are superior to DNA templates in template-directed nonenzymatic primer extension reactions. PMID- 22296306 TI - Effects of myo-inositol in women with PCOS: a systematic review of randomized controlled trials. AB - Polycystic ovary syndrome (PCOS) affects 5%-10% of women in reproductive age, and it is the most common cause of infertility due to ovarian dysfunction and menstrual irregularity. Several studies have reported that insulin resistance is common in PCOS women, regardless of the body mass index. The importance of insulin resistance in PCOS is also suggested by the fact that insulin-sensitizing compounds have been proposed as putative treatments to solve the hyperinsulinemia induced dysfunction of ovarian response to endogenous gonadotropins. Rescuing the ovarian response to endogenous gonadotropins reduces hyperandrogenemia and re establishes menstrual cyclicity and ovulation, increasing the chance of a spontaneous pregnancy. Among the insulin-sensitizing compounds, there is myo inosiol (MYO). Previous studies have demonstrated that MYO is capable of restoring spontaneous ovarian activity, and consequently fertility, in most patients with PCOS. With the present review, we aim to provide an overview on the clinical outcomes of the MYO use as a treatment to improve ovarian function and metabolic and hormonal parameters in women with PCOS. PMID- 22296308 TI - Oral delivery of particulate prostate cancer vaccine: in vitro and in vivo evaluation. AB - BACKGROUND: Various approaches have been evaluated for generation of efficient immune response against tumor antigens. Our approach exploits usage of particulate delivery to generate immune response against prostate cancer antigens. PURPOSE: The aim of this study was to evaluate the efficacy of prostate cancer vaccine derived from a murine prostate cancer cell line, TRAMP C2 in murine model via oral route using aleuria aurantia lectin as a targeting ligand for M-cells in the intestinal Peyer's patches. METHODS: The whole cell lysate (WCL) was obtained from TRAMP C2 murine prostate cancer cell line and was formulated into particles using one step spray drying process. For in vivo studies, 4-6 week old C57BL/6 male mice were vaccinated orally biweekly for 10 weeks. Serum samples were analyzed at regular intervals to determine serum IgG levels. The mice were then challenged with live TRAMP C2 cells to determine efficacy of the vaccine. RESULTS: The serum IgG levels of vaccinated animals were higher compared to that of the controls. Moreover, the tumor growth was retarded significantly in the vaccinated mice compared to that of controls (p < 0.001). CONCLUSIONS: The above findings suggest that oral particulate WCL vaccine can trigger an immune response against prostate cancer antigens. PMID- 22296309 TI - Binding of beta-lactam antibiotics to a bioinspired dizinc complex reminiscent of the active site of metallo-beta-lactamases. AB - Metallo-beta-lactamases (mbetals) cause bacterial resistance toward a broad spectrum of beta-lactam antibiotics by catalyzing the hydrolytic cleavage of the four-membered beta-lactam ring, thus inactivating the drug. Minutiae of the mechanism of these enzymes are still not well understood, and reports about binding studies of the substrates to the enzymes as well as to synthetic model systems are rare. Here we report a new pyrazolate-based bioinspired dizinc complex (1) reminiscent of the active site of binuclear mbetals. Since 1 does not mediate hydrolytic degradation of beta-lactams, the binding of a series of common beta-lactam antibiotics (benzylpenicillin, cephalotin, 6-aminopenicillanic acid, ampicillin) as well as the inhibitor sulbactam and the simplest beta-lactam, 2 azetidinone, to the dizinc core of 1 could now be studied in detail by NMR and IR spectroscopy as well as mass spectrometry. X-ray crystallographic information was obtained for 1 and its complexes with 2-azetidinone (2) and sulbactam (3); the latter represents the first structurally characterized dizinc complex with a bound beta-lactam drug. While 2-azetidinone was found deprotonated and bridging in the clamp of the two zinc ions in 2, in 3 and all other cases the substrates preferentially bind via their carboxylate group within the bimetallic pocket. The relevance of this binding mode for mbetals and consequences for the design of functional model systems are discussed. PMID- 22296310 TI - Evidence of enhanced conjugation in ortho-arylene ethynylenes with transition metal coordination. AB - The effective conjugation of ortho and ortho-alt-para-arylene ethynylenes, with appropriately positioned pyridine and pyrazine heterocycles, increases upon binding to Ag(I) and Pd(II) cations. Significant bathochromic shifts in the electronic spectra, witnessed upon introduction of these metal bridges, are consistent with enhanced electron delocalization in the unsaturated backbone. Control studies suggest that this electronic behavior is attributable exclusively (in the case of Ag(I)) or partially (in the case of Pd(II)) to conformational restrictions of the conjugated backbones. PMID- 22296311 TI - Contrasted resistance of stone-dwelling Geodermatophilaceae species to stresses known to give rise to reactive oxygen species. AB - Stones in arid environments are inhabited by actinobacteria of the family Geodermatophilaceae like the genera Blastococcus and Modestobacter frequently isolated from altered calcarenites. Their habitat requires adaptation to light induced and other stresses that generate reactive oxygen species. Here, we show that representative members of the species Blastococcus saxobsidens, Geodermatophilus obscurus, and Modestobacter multiseptatus are differentially adapted to stresses associated with arid environments. Whereas B. saxobsidens was found to be sensitive to gamma radiation (D(10) = 900 Gy; 10% survival at 900 Gy), M. multiseptatus was moderately (D(10) = 6000 Gy) and G. obscurus was highly tolerant (D(10) = 9000 Gy). A difference in resistance to high-frequency (lambda value = 254 nm) UV was shown by B. saxobsidens, M. multiseptatus, and G. obscurus, being sensitive, tolerant, and highly tolerant (D(10) of 6, 900, and > 3500 kJ m(-2) , respectively). Tolerance to desiccation, mitomycin C and hydrogen peroxide correlated with the ionizing radiation and UV resistance profiles of the three species and were correlated with the pigments synthesized. Resistance to heavy metals/metalloids did not follow the same pattern, with resistance to Ag(2+) and Pb(2+) being similar for B. saxobsidens, M. multiseptatus, and G. obscurus, whereas resistance to AsO4 3-, Cr(2+) , or Cu(2+) was greater for B. saxobsidens than for the other two species. The stress resistance profiles of M. multiseptatus and B. saxobsidens were reflected in different calcarenite colonization patterns. While M. multiseptatus was predominantly isolated from the first two millimeters of stone surface, B. saxobsidens was predominantly isolated from the deeper part of the stone where it is better protected from sun irradiation, suggesting that the response to light- and desiccation-induced oxidative stress is an important driver for niche colonization in the stone biotope. PMID- 22296312 TI - A rare heterozygous TRAF6 variant is associated with hypohidrotic ectodermal dysplasia. AB - BACKGROUND: Mutations in the genes encoding components of the tumour necrosis factor (TNF)-alpha-like pathway cause hypohidrotic ectodermal dysplasia (HED). It has been postulated that the TNF receptor-associated factor 6 (TRAF6) is also involved in this pathway. OBJECTIVES: To investigate mutations in the TRAF6 gene in an individual with HED. METHODS: Genetic analysis was performed on TRAF6 in a patient with HED, her parents, her sister and 150 ethnically matched, healthy individuals. RESULTS: In the patient, sequencing analysis of one DNA strand revealed a deletion of eight nucleotides (c.1074-1081delCAATTTG) in the 5' fragment of the last exon of TRAF6, while no deletion was detected in the other DNA strand indicating a heterozygous mutation. No such sequence abnormality was detected in the patient's parents and her sister. CONCLUSION: This is the first report of a heterozygous TRAF6 sequence variant associated with symptoms typical of HED. PMID- 22296313 TI - The negative impact of global perceptions of and daily care-related family conflict on Hispanic caregivers: familism as a potential moderator. AB - OBJECTIVES: Using selected concepts from Pearlin's care giving stress model and incorporating a daily stress-reactivity perspective, the current study surveyed Hispanic family caregivers (HCGs) to: (a) document the occurrence of family disagreements regarding care; (b) examine the impact of family disagreements regarding care on HCGs' emotional/physical well being; and (c) determine the moderating role of familism - whether strong familism beliefs buffer or exacerbate the negative impact of family disagreements on HCGs. METHODS: Participants (n = 67) reported their daily experiences of family disagreements regarding care, depressive symptoms, feelings of burden, and physical health symptoms on eight consecutive survey days; and, in a separate survey, reported their global perceptions of family disagreements regarding care and their familism beliefs. RESULTS: Multilevel-modeling indicated (a) a significant link between global perceptions of family disagreement regarding care and greater depressive symptoms, feelings of burden, and physical health symptoms and (b) significant moderating (i.e., exacerbating) effects of familism at the daily level suggesting that HCGs with stronger familism beliefs are more reactive to daily care-related family disagreement occurrences. CONCLUSIONS: The findings from the current study suggest that family disagreement regarding care is a salient aspect of the context of care giving for HCGs, and is linked to depressive symptoms, feelings of burden, and physical health symptoms. Familism may play an exacerbating role in this link. Interpretations of the results and implications for research and intervention are offered. PMID- 22296314 TI - Studies of long-term use of antidepressants: how should the data from them be interpreted? AB - Depression is a recurrent illness in which afflicted individuals have an increased risk for recurrence as a function of a greater number of previous episodes. Consequently, prevention of future episodes is central to improving the prognosis. The current recommendation is to use antidepressants over prolonged periods of time to prevent further episodes of depression. However, the database for this practice is limited and can be interpreted in multiple ways. Review of the relevant literature was performed. MEDLINE and PubMed databases were searched from inception to 5 September 2011 for randomized, placebo-controlled trials of at least 18 months duration. After treatment of an acute depressive episode, antidepressants clearly prevent relapse back into the same depressive episode. This is demonstrated by an adequate number of randomized, blinded, placebo controlled, 1-year continuation trials. The ability of antidepressants to prevent recurrence of future episodes is less clear. Randomized, blinded, placebo controlled trials of 18 months or longer are infrequent - 18 studies were identified. While nearly all show that antidepressant continuation is superior to placebo in preventing resurgence of depressive symptoms, nearly all of the difference occurs in the first 6 months after randomization. This pattern strongly suggests that the apparent superiority of antidepressants may be due to (i) their ability to prevent recurrence, (ii) antidepressant withdrawal (characterized by depressive symptoms) in patients switched to placebo or (iii) a combination of these phenomena. PMID- 22296315 TI - Depression following traumatic brain injury: epidemiology, risk factors and management. AB - It is important for clinicians to recognize major depression following traumatic brain injury (TBI) because of its association with poor global and psychosocial outcome, postconcussive symptoms and cognitive deficits. The purpose of this review is to provide an up-to-date selective review of the current understanding of epidemiology, risk factors and management of major depression following TBI. Many studies of prevalence of depression following TBI have not used accepted structured criteria for the diagnoses, but those that did found wide ranges of rates, from 17% to 61%. The risk factors for development of depression following TBI are poorly understood, but past psychiatric history, frontal lesions and atrophy, and family dysfunction have been shown in more than one study to play important roles. There are few controlled trials of the treatment of major depression in patients with TBI using accepted diagnostic criteria for major depression, as well as defined criteria for response and remission. As such, it is important for clinicians to use best practice guidelines for the treatment of major depression in the absence of TBI. PMID- 22296316 TI - The role of antipsychotics in the management of fibromyalgia. AB - Fibromyalgia is a syndrome characterized by chronic generalized pain associated with different somatic symptoms, such as sleep disturbances, fatigue, stiffness, balance problems, hypersensitivity to physical and psychological environmental stimuli, depression and anxiety. It has been estimated to affect roughly the 2-4% of the general population in most countries studied, and it has been shown to be much more prevalent in women than in men. Although its pathophysiology is not yet fully understood, it is known that both genetic and environmental factors are involved in its development. Fibromyalgia shares a high degree of co-morbidity with other conditions, including chronic headache, temporomandibular disorder, irritable bowel syndrome, major depression, anxiety disorders and chronic fatigue syndrome. Therefore, this is a syndrome difficult to treat for which multimodal treatments including physical exercise, psychological therapies and pharmacological treatment are recommended. Although different kinds of drugs have been studied for the treatment of fibromyalgia, the most widely used drugs that have the higher degree of evidence for efficacy include the alpha(2)delta ligands pregabalin and gabapentin, and the tricyclic antidepressants (TCAs) and serotonin noradrenaline (norepinephrine) reuptake inhibitors (SNRIs). However, there is a need to look for newer additional therapeutic pharmacological options for the treatment of this complex and disabling disease. First- and second-generation antipsychotics have shown analgesic properties both in an experimental setting and in humans, although most of the available evidence for the treatment of human pain concerns older antipsychotics and involves clinical trials performed several decades ago. In addition, several second-generation antipsychotics, risperidone, olanzapine and quetiapine, have shown efficacy in the treatment of some anxiety disorders. Some second-generation antipsychotics, mainly quetiapine, aripiprazole and amisulpride, have demonstrated antidepressant activity, with quetiapine approved for the treatment of bipolar depression and refractory major depression, and aripiprazole approved as an adjunctive treatment for major depressive disorder. Finally, several old and new antipsychotics, including promethazine, levopromazine, olanzapine, quetiapine and ziprasidone, have been shown to improve sleep parameters in healthy subjects. Each of these properties suggests that antipsychotics could represent a new potential alternative for the treatment of fibromyalgia syndrome. To date, most of the published studies on the use of antipsychotics in the treatment of fibromyalgia syndrome have been uncontrolled, either case reports or case series, dealing with olanzapine, quetiapine, ziprasidone, levopromazine and amisulpride. The studies on olanzapine and quetiapine have suggested therapeutic efficacy although, in the case of olanzapine, hampered by tolerability problems. A double-blind controlled trial, published in 1980, showed that chlorpromazine increased slow-wave sleep and improved pain and mood disturbances. More recently, four double-blind controlled studies have explored the efficacy of quetiapine, either alone or as an add-on treatment, in fibromyalgia management. None of these trials has yet been published, although two of them have been presented as congress communications, both of them suggesting that quetiapine could be a potential alternative treatment for fibromyalgia. In summary, the current available evidence suggests that at least some antipsychotics, specifically quetiapine, could be useful for the treatment of fibromyalgia and that further studies on the efficacy of these compounds are worth pursuing. PMID- 22296317 TI - Aripiprazole: a review of its use in the management of schizophrenia in adults. AB - Oral aripiprazole (Abilify(r)) is an atypical antipsychotic agent that is approved worldwide for use in adult patients with schizophrenia. It is a quinolinone derivative that has a unique receptor binding profile as it exhibits both partial agonist activity at dopamine D(2) receptors and serotonin 5-HT(1A) receptors and antagonist activity at 5-HT(2A) receptors. In several well designed, randomized, clinical trials of 4-6 weeks duration, aripiprazole provided symptomatic control for patients with acute, relapsing schizophrenia or schizoaffective disorder. Furthermore, following 26 weeks' treatment, the time to relapse was significantly longer for patients with chronic, stabilized schizophrenia receiving aripiprazole compared with those receiving placebo. Using a variety of efficacy outcomes, aripiprazole showed a mixed response when evaluated against other antipsychotic agents in randomized clinical trials. Longer-term data showed that improvements in remission rates and response rates favoured aripiprazole over haloperidol, although, the time to failure to maintain a response was not significantly different between the treatment arms. On the other hand, improvements in positive and negative symptom scores mostly favoured olanzapine over aripiprazole, although, the time to all-cause treatment discontinuation was not significantly different between the two treatments. Several open-label, switching trials showed that aripiprazole provided continued control of symptoms in patients with schizophrenia or schizoaffective disorder. Using a variety of efficacy outcomes or quality-of-life scores, longer-term treatment generally favoured patients switched to receive aripiprazole compared with standard-of-care oral antipsychotics. Aripiprazole was generally well tolerated in patients with schizophrenia. In particular, its use seems to be associated with a lower incidence of extrapyramidal symptoms than haloperidol and fewer weight-gain issues than olanzapine. Aripiprazole also showed a favourable cardiovascular tolerability profile and its use was associated with a reduced risk of metabolic syndrome than placebo or olanzapine. As a consequence, aripiprazole may provide a more cost-effective treatment option compared with other atypical antipsychotics. In conclusion, oral aripiprazole provides an effective and well tolerated treatment alternative for the acute and long-term management of patients with schizophrenia. PMID- 22296318 TI - The need to develop more sensitive tools to accurately detect clinical response to treatment in ADHD. PMID- 22296320 TI - Sequence-regulated copolymers via tandem catalysis of living radical polymerization and in situ transesterification. AB - Sequence regulation of monomers is undoubtedly a challenging issue as an ultimate goal in polymer science. To efficiently produce sequence-controlled copolymers, we herein developed the versatile tandem catalysis, which concurrently and/or sequentially involved ruthenium-catalyzed living radical polymerization and in situ transesterification of methacrylates (monomers: RMA) with metal alkoxides (catalysts) and alcohols (ROH). Typically, gradient copolymers were directly obtained from the synchronization of the two reactions: the instantaneous monomer composition in feed gradually changed via the transesterification of R(1)MA into R(2)MA in the presence of R(2)OH during living polymerization to give R(1)MA/R(2)MA gradient copolymers. The gradient sequence of monomers along a chain was catalytically controlled by the reaction conditions such as temperature, concentration and/or species of catalysts, alcohols, and monomers. The sequence regulation of multimonomer units was also successfully achieved in one-pot by monomer-selective transesterification in concurrent tandem catalysis and iterative tandem catalysis, providing random-gradient copolymers and gradient block counterparts, respectively. In contrast, sequential tandem catalysis via the variable initiation of either polymerization or in situ transesterification led to random or block copolymers. Due to the versatile adaptability of common and commercially available reagents (monomers, alcohols, catalysts), this tandem catalysis is one of the most efficient, convenient, and powerful tools to design tailor-made sequence-regulated copolymers. PMID- 22296322 TI - Strategies for the management of intermittent allergic rhinitis: an Australian study. AB - OBJECTIVE: Allergic rhinitis is increasing globally despite treatment focussed on pharmacotherapy. This study aimed to (i) examine the range and proportion of symptoms and triggers experienced by patients with intermittent allergic rhinitis (IAR); (ii) conduct a qualitative analysis of strategies devised to control symptoms and triggers; and (iii) measure medication adherence. METHODS: A qualitative and observational study of data drawn from a randomized controlled trial on patients with IAR. Strategies collaboratively devised by participants and pharmacist staff to minimize symptoms and triggers were analysed thematically. In the 10-day observational study, the participants recorded all symptoms and triggers of IAR along with use of medications and these were analysed descriptively. RESULTS: Number of 124 participants recorded 620 symptoms and identified 357 triggers of IAR. To minimize these, 579 strategies were devised in consultation with pharmacy staff. The frequency and type of strategy varied according to whether the goals were aimed at controlling symptoms or triggers. Adherence to a course of antihistamines over the 10-day trial was self reported by participants with 36% indicating full adherence. CONCLUSION: A large number and range of symptoms and triggers were identified, and individualized strategies were devised to minimize symptoms and triggers. Medication adherence was poor. PRACTICE IMPLICATIONS: Patients with IAR can be assisted to identify their symptoms and triggers and develop relevant strategies to manage these. This approach has the potential to facilitate patient self-management of a chronic and incapacitating condition. PMID- 22296323 TI - Event sequencing of forced intramuscular medication in England. AB - In most inpatient psychiatric care systems it is permissible in certain situations for staff to forcibly inject patients with psychotropic medication. The aim of this study is to describe what precedes and follows a coerced intramuscular injection within a nursing shift. Data were collected on the sequence of conflict (aggression, absconding, etc.) and containment (seclusion, restraint, etc.) for the first 2 weeks of 522 acute admissions on 84 wards in 31 UK hospitals. Injections were given to 9% of patients. Aggression, regular medication refusal and pro re nata (PRN) medication refusal preceded injections. The giving of coerced medication concluded most crises. Coerced medication effectively resolves crises in the short term. Staff should offer oral PRN as an alternative, unless this is unsafe. Where only verbal violence has occurred staff should try to resolve the crisis without enforcing medication. More research on the best way to respond to inpatients' medication refusal is required. PMID- 22296324 TI - The importance of ERalpha and ERbeta gene polymorphisms in PCOS. AB - Estrogens act through binding to estrogen receptor alpha (ERalpha) and beta (ERbeta). Studies in knockout mice have shown that the absence of ERalpha leads to the polycystic ovary syndrome (PCOS) phenotype. Furthermore, the expression of ERbeta gene is lower in follicles derived from women with PCOS compared with healthy women. The aim of this study was to investigate the importance of ERalpha and ERbeta gene polymorphisms in PCOS. A cohort of 180 women with PCOS and 140 healthy controls were recruited, and the PvuII and XbaI polymorphisms of ERalpha, as well as, the AluI and RsaI polymorphisms of ERbeta were genotyped. No difference was found in the distribution of these polymorphisms between patients and healthy controls. However, in PCOS women, carriers of TC and TT genotypes of PvuII polymorphism had lower fasting glucose to insulin ratio compared with carriers of CC genotype (p = 0.029). In addition, the presence of AA genotype of XbaI polymorphism was associated with lower levels of follicle-stimulating hormone (FSH) compared with the presence of AG and GG genotypes (p = 0.03). The association of ERalpha polymorphisms with insulin resistance indices and FSH levels emphasizes the importance of ERalpha as a genetic modifier of the PCOS phenotype. PMID- 22296326 TI - Membrane protein-lipid selectivity: enhancing sensitivity for modeling FRET data. AB - Forster resonance energy transfer (FRET) is a powerful method for the characterization of membrane proteins lipid selectivity. FRET can be used to quantify distances between a single donor and a single acceptor molecule; however, for FRET donors and acceptors scattered in the bilayer plane, multiple donor-acceptor pairs and distances are present. In addition, when studying protein/lipid selectivity, for a single tryptophan used as a donor; several lipid acceptors may be located at the boundary region (annular lipids) of the protein. Therefore, in these experiments, a theoretical analysis based on binomial distribution of multiple acceptors around the membrane proteins is required. In this work, we performed FRET measurements between single tryptophan lactose permease (W151/C154G LacY) of Escherichia coli and pyrene-labeled phospholipids (Pyr-PE, Pyr-PG, and Pyr-PC) reconstituted in palmitoyl-2-oleoyl-sn-glycero-3 phosphoethanolamine, 1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (sodium salt), 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-choline, and 1,2 dioleoyl-sn-glycero-3-phospho-choline at 25 and 37 degrees C. To increase the sensitivity of the method and to ascertain the lipid selectivity for LacY, we reconstituted the protein in the pure phospholipids doped with 1.5% of labeled phospholipids. From fitting the theoretical model to the experimental FRET efficiencies, two parameters were calculated: the probability of a site in the annular ring being occupied by a labeled pyrene phospholipid and the relative association constant between the labeled and unlabeled phospholipids. The experimental FRET efficiencies have been interpreted taking into account the particular folding of the protein in each phospholipid matrix. Additional information on the annular lipid composition for each system has been obtained by exciting W151/C154G LacY and monitoring the emission intensities for monomer and excimer of the pyrene spectra. The results obtained indicate a higher selectivity of LacY for PE over PG and PC and pointed to a definite role of the acyl chains in the overall phospholipid-protein interaction. PMID- 22296327 TI - A technology-aided program to support leisure engagement and communication by a man with amyotrophic lateral sclerosis. AB - OBJECTIVE: To assess a technology-aided programme for promoting leisure engagement and communication in a man with amyotrophic lateral sclerosis (ALS). METHOD: The programme involved a laptop computer equipped with a Clicker 5 software package, an optic microswitch and an interface device. The participant could choose between two leisure options (i.e. songs and videos), could write requests and general messages through a virtual keyboard and a microswitch and could have the written text read out to caregivers and staff. RESULTS: The use of the programme increased the mean frequency of words written to about 15 per 20 minute session during the second intervention phase. Those words were used by the participant for formulating a mean of over two requests/messages per session. The participant also listened to songs and watched videos. CONCLUSION: A simple technology-aided programme may allow ALS patients to manage leisure engagement and communication. PMID- 22296328 TI - Do thick leaves avoid thermal damage in critically low wind speeds? AB - Transient lulls in air movement are rarely measured, but can cause leaf temperature to rise rapidly to critical levels. The high heat capacity of thick leaves can damp this rapid change in temperature. However, little is known about the extent to which increased leaf thickness can reduce thermal damage, or how thick leaves would need to be to have biological significance. We evaluated quantitatively the contribution of small increases in leaf thickness to the reduction in thermal damage during critically low wind speeds under desert conditions. We employed a numerical model to investigate the effect of thickness relative to transpiration, absorptance and leaf size on damage avoidance. We used measured traits and thermotolerance thresholds of real leaves to calculate the leaf temperature response to naturally occurring variable low wind speed. Our results demonstrated that an increase in thickness of only fractions of a millimetre can prevent excursions to damaging high temperatures. This damping effect of increased thickness was greatest when other means of reducing leaf temperature (transpiration, reflectance or reduced size) were lacking. For perennial desert flora, we propose that increased leaf thickness is important in decreasing the incidence of extreme heat stress and, in some species, in enhancing long-term survival. PMID- 22296329 TI - Hsp33 confers bleach resistance by protecting elongation factor Tu against oxidative degradation in Vibrio cholerae. AB - The redox-regulated chaperone Hsp33 protects bacteria specifically against stress conditions that cause oxidative protein unfolding, such as treatment with bleach or exposure to peroxide at elevated temperatures. To gain insight into the mechanism by which expression of Hsp33 confers resistance to oxidative protein unfolding conditions, we made use of Vibrio cholerae strain O395 lacking the Hsp33 gene hslO. We found that this strain, which is exquisitely bleach sensitive, displays a temperature-sensitive (ts) phenotype during aerobic growth, implying that V. cholerae suffers from oxidative heat stress when cultivated at 43 degrees C. We utilized this phenotype to select for Escherichia coli genes that rescue the ts phenotype of V. cholerae DeltahslO when overexpressed. We discovered that expression of a single protein, the elongation factor EF-Tu, was sufficient to rescue both the ts and bleach-sensitive phenotypes of V. cholerae DeltahslO. In vivo studies revealed that V. cholerae EF-Tu is highly sensitive to oxidative protein degradation in the absence of Hsp33, indicating that EF-Tu is a vital chaperone substrate of Hsp33 in V. cholerae. These results suggest an 'essential client protein' model for Hsp33's chaperone action in Vibrio in which stabilization of a single oxidative stress-sensitive protein is sufficient to enhance the oxidative stress resistance of the whole organism. PMID- 22296330 TI - Transition state analysis of Vibrio cholerae sialidase-catalyzed hydrolyses of natural substrate analogues. AB - A series of isotopically labeled natural substrate analogues (phenyl 5-N-acetyl alpha-d-neuraminyl-(2->3)-beta-d-galactopyranosyl-(1->4)-1-thio-beta-d glucopyranoside; Neu5Acalpha2,3LacbetaSPh, and the corresponding 2->6 isomer) were prepared chemoenzymatically in order to characterize, by use of multiple kinetic isotope effect (KIE) measurements, the glycosylation transition states for Vibrio cholerae sialidase-catalyzed hydrolysis reactions. The derived KIEs for Neu5Acalpha2,3LacbetaSPh for the ring oxygen ((18)V/K), leaving group oxygen ((18)V/K), C3-S deuterium ((D)V/K(S)) and C3-R deuterium ((D)V/K(R)) are 1.029 +/ 0.002, 0.983 +/- 0.001, 1.034 +/- 0.002, and 1.043 +/- 0.002, respectively. In addition, the KIEs for Neu5Acalpha2,6betaSPh for C3-S deuterium ((D)V/K(S)) and C3-R deuterium ((D)V/K(R)) are 1.021 +/- 0.001 and 1.049 +/- 0.001, respectively. The glycosylation transition state structures for both Neu5Acalpha2,3LacbetaSPh and Neu5Acalpha2,6LacbetaSPh were modeled computationally using the experimental KIE values as goodness of fit criteria. Both transition states are late with largely cleaved glycosidic bonds coupled to pyranosyl ring flattening ((4)H(5) half-chair conformation) with little or no nucleophilic involvement of the enzymatic tyrosine residue. Notably, the transition state for the catalyzed hydrolysis of Neu5Acalpha2,6betaSPh appears to incorporate a lesser degree of general-acid catalysis, relative to the 2,3-isomer. PMID- 22296331 TI - Sulfidation of silver nanoparticles decreases Escherichia coli growth inhibition. AB - Sulfidation of metallic nanoparticles such as silver nanoparticles (AgNPs) released to the environment may be an important detoxification mechanism. Two types of AgNPs-an engineered polydisperse and aggregated AgNP powder, and a laboratory-synthesized, relatively monodisperse AgNP aqueous dispersion-were studied. The particles were sulfidized to varying degrees and characterized to determine the effect of initial AgNP polydispersity and aggregation state on AgNP sulfidation, and then exposed to Escherichia coli to determine if the degree of sulfidation of pristine AgNPs affects growth inhibition of bacteria. The extent of sulfidation was found to depend on the HS(-)/Ag ratio. However, for the same reaction times, the more monodisperse particles were fully transformed to Ag(2)S, and the polydisperse, aggregated particles were not fully sulfidized, thus preserving the toxic potential of Ag(0) in the aggregates. A higher Ag(2)S:Ag(0) ratio in the sulfidized nanoparticles resulted in less growth inhibition of E. coli over 6 h of exposure. These results suggest that the initial properties of AgNPs can affect sulfidation products, which in turn affect microbial growth inhibition, and that these properties should be considered in assessing the environmental impact of AgNPs. PMID- 22296332 TI - Rapid evolution of body fluid regulation following independent invasions into freshwater habitats. AB - Colonizations from marine to freshwater environments constitute among the most dramatic evolutionary transitions in the history of life. Colonizing dilute environments poses great challenges for acquiring essential ions against steep concentration gradients. This study explored the evolution of body fluid regulation following freshwater invasions by the copepod Eurytemora affinis. The goals of this study were to determine (1) whether invasions from saline to freshwater habitats were accompanied by evolutionary shifts in body fluid regulation (hemolymph osmolality) and (2) whether parallel shifts occurred during independent invasions. We measured hemolymph osmolality for ancestral saline and freshwater invading populations reared across a range of common-garden salinities (0.2-25 PSU). Our results revealed the evolution of increased hemolymph osmolality (by 16-31%) at lower salinities in freshwater populations of E. affinis relative to their saline ancestors. Moreover, we observed the same evolutionary shifts across two independent freshwater invasions. Such increases in hemolymph osmolality are consistent with evidence of increased ion uptake in freshwater populations at low salinity, found in a previous study, and are likely to entail increased energetic costs upon invading freshwater habitats. Our findings are consistent with the evolution of increased physiological regulation accompanying transitions into stressful environments. PMID- 22296333 TI - Coal-tar-based pavement sealcoat and PAHs: implications for the environment, human health, and stormwater management. AB - Coal-tar-based sealcoat products, widely used in the central and eastern U.S. on parking lots, driveways, and even playgrounds, are typically 20-35% coal-tar pitch, a known human carcinogen that contains about 200 polycyclic aromatic hydrocarbon (PAH) compounds. Research continues to identify environmental compartments-including stormwater runoff, lake sediment, soil, house dust, and most recently, air-contaminated by PAHs from coal-tar-based sealcoat and to demonstrate potential risks to biological communities and human health. In many cases, the levels of contamination associated with sealed pavement are striking relative to levels near unsealed pavement: PAH concentrations in air over pavement with freshly applied coal-tar-based sealcoat, for example, were hundreds to thousands of times higher than those in air over unsealed pavement. Even a small amount of sealcoated pavement can be the dominant source of PAHs to sediment in stormwater-retention ponds; proper disposal of such PAH-contaminated sediment can be extremely costly. Several local governments, the District of Columbia, and the State of Washington have banned use of these products, and several national and regional hardware and home-improvement retailers have voluntarily ceased selling them. PMID- 22296334 TI - Prostate-specific antigen velocity (PSAV) risk count improves the specificity of screening for clinically significant prostate cancer. AB - OBJECTIVE: * To determine whether the prostate-specific antigen velocity (PSAV) risk count (i.e. the number of times PSAV exceeds a specific threshold) could increase the specificity of screening for prostate cancer and potentially life threatening tumours. PATIENTS AND METHODS: * From 1989 to 2001, we calculated two serial PSAV measurements in 18 214 prostate cancer screening-study participants, of whom 1125 (6.2%) were diagnosed with prostate cancer. * The PSAV risk count was determined as the number of PSAV measurements of >0.4 ng/mL/year (0, 1, or 2). * We used receiver operating characteristic (ROC) and reclassification analyses to examine the ability of PSAV risk count to predict screen-detected and high-grade prostate cancer. RESULTS: * The PSAV was >0.4 ng/mL/year twice (risk count 2) in 40% of prostate cancer cases compared with only 4% of those with no cancer (P < 0.001). * After adjusting for age and PSA level, a PSAV risk count of 2 was associated with an 8.2-fold increased risk of prostate cancer (95% confidence interval 7.0-9.6, P < 0.001) and 5.4-fold increased risk of Gleason score 8-10 prostate cancer on biopsy. * Compared with a model with age and PSA level, the addition of the PSAV risk count significantly improved discrimination (area under the ROC curve 0.625 vs 0.725, P= 0.031) and reclassified individuals for the risk of high-grade prostate cancer (net reclassification, P < 0.001). CONCLUSIONS: * Sustained rises in PSA indicate a significantly greater risk of prostate cancer, particularly high-grade disease. * Compared with men with a risk count of <=1, those with two PSAV measurements of >0.4 ng/mL/year (risk count 2) had an 8-fold increased risk of prostate cancer and 5.4-fold increased risk of Gleason 8-10 disease on biopsy, adjusting for age and PSA level. * Compared to PSA alone, PSAV risk count may be useful in reducing unnecessary biopsies and the diagnosis of low-risk prostate cancer. PMID- 22296335 TI - Abnormally long-range diamagnetic anisotropy induced by cyclic d(delta)-p(pi) pi conjugation within a six-membered dimolybdenum/chalcogen ring. AB - Incorporating two quadruply bonded dimolybdenum units [Mo(2)(DAniF)((3))](+) (ancillary ligand DAniF = N,N'-di-p-anisylformamidinate) with two hydroselenides (SeH(-)) gave rise to [Mo(2)(DAniF)(3)](2)(MU-SeH)(2) (1). With the molecular scaffold remaining unchanged, aerobic oxidation of 1, followed by autodeprotonation, generated [Mo(2)(DAniF)(3)](2)(MU-Se)(2) (2). The two complexes share a common cyclic six-membered Mo(2)/Se core, but compound 2 is distinct from 1 by having structural, electronic, and magnetic properties that correspond with aromaticity. Importantly, the aromatic behaviors for this non carbon system are ascribable to the bonding analogy between the delta component in a Mo-Mo quadruple bond and the pi component in a C-C double bond. Cyclic pi delocalization via d(delta)-p(pi) conjugation within the central unit, which involves six pi electrons with one electron from each of the Mo(2) units and two electrons from each of the bridging atoms, has been confirmed in a previous work on the oxygen- and sulfur-bridged analogues (Fang, W.; et al. Chem.-Eur. J.2011, 17, 10288). Of the three members in this family, compound 2 exhibits an enhanced aromaticity because of the selenium bridges. The remote in-plane and out-of-plane methine (ArNCHNAr) protons resonate at chemical shifts (delta) 9.42 and 7.84 ppm, respectively. This NMR displacement, Deltadelta = 1.58 ppm, is larger than that for the oxygen-bridged (1.30 ppm) and sulfur-bridged (1.49 ppm) derivatives. The abnormally long-range shielding effects and the large diamagnetic anisotropy for this complex system can be rationalized by the induced ring currents circulating the Mo(2)/chalcogen core. By employment of the McConnell equation {Deltasigma = Deltachi[(l - 3 cos 2theta)/3R(3)N]}, the magnetic anisotropy (Deltachi = chi(?) chi(||)) is estimated to be -414 ppm cgs, which is dramatically larger than 62.9 ppm cgs for benzene, the paradigm of aromaticity. In addition, it is found that the magnitude of Deltachi is linearly related to the radius of the bridging atoms, with the selenium analogue having the largest value. This aromaticity sequence is in agreement with that for the chalcogen-containing aromatic family, e.g., furan < thiophene < selenophene. PMID- 22296336 TI - Chitosan nanoparticles: a survey of preparation methods. AB - The application of macromolecules in therapy is frequently hindered by stability and/or permeation issues. These limitations have been addressed by the pharmaceutical industry through the development of suitable noninjectable drug carriers. In this context, nanoparticles have emerged as one of the most exciting tools due to the increased surface-to-volume ratio, which provides an intimate interaction with epithelial surfaces. Nanoparticles further enable the encapsulated molecules to retain their biological activity, from the production steps to the final release. Chitosan has reached a prominent position as carrier forming material, as diverse methods can be applied to produce nanoparticles using that excipient. These involve either hydrophilic or lipophilic environments that generally result in mild conditions or aggressive and time-consuming processes, respectively. In this review, a detailed description of methods used to produce chitosan nanocarriers is provided, accompanied by illustrative schemes of the procedures. The emphasis is on the variables reported to affect the final properties of the vehicles. PMID- 22296337 TI - Self- and other-oriented potential lifetime traumatic events as predictors of loneliness in the second half of life. AB - OBJECTIVES: This study examined the relationship between self- and other-oriented potential lifetime traumatic events (PLTE) and loneliness at the second half of life. METHOD: The sample was comprised of 7446 respondents who completed the Health and Retirement Study (HRS) 2006 psychosocial questionnaire. PLTE were classified into self-oriented PLTE, defined as traumatic events that primarily inflict the self (e.g., being abused by parents) and other-oriented PLTE, defined as events that affect the self by primarily targeting others (e.g., death of one's child). We evaluated the role of self- and other-oriented PLTE as predictors of loneliness, as evaluated by the short R-UCLA. Analyses were stratified by age at which trauma happened categorized into four life periods (0 17, 18-30, 31-49, 50+). RESULTS: The results showed that PLTE is positively related to loneliness. Moreover, the number of other-oriented PLTE, and even more pronouncedly self-oriented PLTE, that happened up until adulthood were the strongest predictors of loneliness at the second half of life. CONCLUSION: The study suggests that self- and other-oriented PLTE reported to have occurred early in life are associated with perceived loneliness in the second half of life. PMID- 22296338 TI - Burkitt lymphoma: staging and response evaluation. AB - The refinements in both the staging and response evaluation of children with Burkitt lymphoma (BL) have contributed to the improvements in treatment outcome observed over the past 40 years. Ziegler and Magrath designed a staging system in the 1970s for children with BL in equatorial Africa. Currently, the most widely used staging system around the world is that described by Murphy in 1980, which was developed for children with non-Hodgkin lymphoma (NHL) of any histology. There are opportunities for refinement in this system, particularly with respect to certain extra-nodal sites, such as skin and bone. The findings obtained at diagnosis with novel technologies (functional imaging [e.g., positron emission tomography [PET]] and minimal residual disease [MRD] technology), which are more sensitive with respect to disease detection than historic modalities, also need to be considered. Technological advances have also had impact on the assessment of response evaluation. Standard x-rays were routinely used in the 1960s; nuclear imaging became widely used in the 1970s; computerized axial tomography was incorporated in the 1980s; PET imaging was incorporated and, in many cases, has replaced gallium/bone scans since 2000; and MRD technology has been explored in some of the most recent clinical trials. There is clearly a need for more clinical data on the use of PET and MRD technology in the determination of response evaluation of children with BL as well as other histological subtypes of NHL. An international working group is currently addressing the refinement of both disease staging and response evaluation in children with NHL. PMID- 22296339 TI - Seasonal variation in the function and diversity of methanotrophs in the littoral wetland of a boreal eutrophic lake. AB - Littoral wetlands are responsible for most of the total methane (CH(4) ) emissions from lake ecosystems. We show that seasonally variable hydrological and temperature conditions in the littoral wetland of a eutrophic boreal lake affect the community composition and gene transcription of methanotrophs measured by a particulate methane monooxygenase (pmoA) gene-targeted microarray. Type Ib freshwater-cluster methanotrophs were favoured by the high water level, and CH(4) oxidation was positively correlated with their pmoA gene transcripts. In the dry subsite of the wetland, the more stagnant hydrological conditions in summer and autumn induced the dominance of type II methanotrophs over type I methanotrophs (community composition and pmoA gene transcripts). The relative abundance of type II methanotrophs increased in winter. The results provide new insight into the variation of methanotroph communities across seasons in littoral wetlands. PMID- 22296341 TI - Input-dependent induction of oligonucleotide structural motifs for performing molecular logic. AB - The K(+)-H(+)-triggered structural conversion of multiple nucleic acid helices involving duplexes, triplexes, G-quadruplexes, and i-motifs is studied by gel electrophoresis, circular dichroism, and thermal denaturation. We employ the structural interconversions for perfoming molecular logic operations, as verified by fluorimetry and colorimetry. Short G-rich and C-rich cDNA and RNA single strands are hybridized to produce four A-form and B-form duplexes. Addition of K(+) triggers the unwinding of the duplexes by inducing the folding of G-rich strands into DNA- or RNA G-quadruplex mono- and multimers, respectively. We found a decrease in pH to have different consequences on the resulting structural output, depending on whether the C-rich strand is DNA or RNA: while the protonated C-rich DNA strand folds into at least two isomers of a stable i-motif structure, the protonated C-rich RNA strand binds a DNA/RNA hybrid duplex to form a Y.RY parallel triplex. When using K(+) and H(+) as external stimuli, or inputs, and the induced G-quadruplexes as reporters, these structural interconversions of nucleic acid helices can be employed for performing logic-gate operations. The signaling mode for detecting these conversions relies on complex formation between DNA or RNA G-quadruplexes (G4) and the cofactor hemin. The G4/hemin complexes catalyze the H(2)O(2)-mediated oxidation of peroxidase substrates, resulting in a fluorescence or color change. Depending on the nature of the respective peroxidase substrate, distinct output signals can be generated, allowing one to operate multiple logic gates such as NOR, INH, or AND. PMID- 22296342 TI - Managing distressed and disturbed patients: the thoughts and feelings experienced by Italian nurses. AB - This paper reports on a qualitative study to identify Italian nurses' feelings and emotions towards the management of distressed and disturbed psychiatric patients in acute inpatient settings. Four focus groups were carried out involving 33 nurses from seven acute psychiatric services in a region of Italy. Data were analysed using content analysis. Findings highlight that fear is the prevailing feeling experienced by nurses in the management of distressed patients. This includes both fear of being physically harmed and concerns about doing harm or damage to patients. The unpredictability of aggressive behaviour from unknown patients was described as especially frightening. Known patients, namely those previously admitted to the unit, induced less fear, as their behaviour was considered more predictable. Patients with dual diagnosis were also a worry for many nurses, who considered themselves lacking in the personal relational skills needed to manage an individual in crisis. Nurses reported that they try to understand the reasons for a patient's aggressive behaviour and are empathetic to his or her suffering. When such empathy is lacking, nurses experience conflicting feelings of counter-aggressiveness. The paper concludes by emphasizing the need to increase availability of education related to patient management, in particular team working and its internal relationships. PMID- 22296343 TI - Markers of low-grade inflammation, breastfeeding and uric acid concentration. PMID- 22296344 TI - Short- and long-term effects of synchronized metronome training in children with hemiplegic cerebral palsy: a two case study. AB - BACKGROUND: Children with cerebral palsy (CP) require individualized long-term management to maintain and improve motor functions. The objective of this study was to explore potential effects of synchronized metronome training (SMT) on movement kinematics in two children diagnosed with spastic hemiplegic CP (HCP). METHOD: Both children underwent 4-weeks/12 sessions of SMT by means of the Interactive Metronome (IM). Optoelectronic registrations of goal-directed uni- and bimanual upper-limb movements were made at three occasions; pre-training, post completed training and at 6-months post completed training. RESULTS: Significant changes in kinematic outcomes following IM training were found for both cases. Findings included smoother and shorter movement trajectories in the bimanual condition, especially for the affected side. In the unimanual condition, Case I also showed increased smoothness of the non-affected side. CONCLUSIONS: The observed short- and long-term effects on the spatio-temporal organization of upper-limb movements need to be corroborated and extended by further case-control studies. PMID- 22296345 TI - Aerial development in Streptomyces coelicolor requires sortase activity. AB - Streptomyces coelicolor is a multicellular bacterium whose life cycle encompasses three differentiated states: vegetative hyphae, aerial hyphae and spores. Among the factors required for aerial development are the 'chaplins', a family of eight secreted proteins that coat the surface of aerial hyphae. Three chaplins (the 'long' chaplins, ChpA, B and C) possess an LAXTG-containing C-terminal sorting signal and are predicted sortase substrates. The five remaining 'short' chaplins are presumed to be associated with the cell surface through interactions with the long chaplins. We show here that two sortase enzymes, SrtE1 and SrtE2, cleave LAXTG-containing peptides at two distinct positions in vitro, and are required for cell wall anchoring of ChpC in vivo. srtE1/E2 double mutants are delayed in aerial hyphae formation, do not sporulate and fail to display all short chaplins on their aerial surfaces. Surprisingly, these mutant characteristics were not shared by a long chaplin mutant, which exhibited only modest delays in aerial development, leading us to revise the current model of chaplin-mediated aerial development. The sortase mutant phenotype, instead, appears to stem from an inability to transcribe aerial hyphae-specific genes, whose products have diverse functions. This suggests that sortase activity triggers an important, and previously unknown, developmental checkpoint. PMID- 22296346 TI - Role of dense shelf water cascading in the transfer of organochlorine compounds to open marine waters. AB - Settling particles were collected by an array of sediment trap moorings deployed along the Cap de Creus (CCC) and Lacaze-Duthiers (LDC) submarine canyons and on the adjacent southern open slope (SOS) between October 2005 and October 2006. This array collected particles during common settling processes and particles transferred to deep waters by dense shelf water cascading (DSWC). Polychlorobiphenyls (PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), chlorobenzenes (CBzs)--pentachlorobenzene and hexachlorobenzene--and hexachlorocyclohexanes were analyzed in all samples. The results show much higher settling fluxes of these compounds during DSWC than during common sedimentation processes. The area of highest deposition was located between 1000 and 1500 m depth and extended along the canyons and outside them showing their channelling effects but also overflows of dense shelf water from these canyons. Higher fluxes were observed near the bottom (30 m above bottom; mab) than at intermediate waters (500 mab) which is consistent with the formation and sinking of dense water close to the continental shelf and main displacement through the slope by the bottom. DSWC involved the highest settling fluxes of these compounds ever described in marine continental slopes and pelagic areas, e.g., peak values of PCBs (960 ng . m(-2) . d(-1)), DDTs (2900 ng . m(-2) . d(-1)), CBzs (340 ng . m( 2) . d(-1)) and lindane (180 ng . m(-2) . d(-1)). PMID- 22296347 TI - A prospective pilot study of ultrasound therapy effectiveness in refractory venous leg ulcers. AB - Venous insufficiency is the most common cause of leg ulcers in the United States. Venous leg ulcers cost the health care system billions of dollars annually, and healing rates are less than 70% with standard of care; therefore, new therapies are needed to increase healing times and minimize associated costs. Non contact ultrasound therapy has been used to treat a variety of chronic wounds including venous leg ulcers, and it is thought that ultrasound has an effect on decreasing the bacterial count in wounds, although the exact mechanism of action of ultrasound is yet to be determined. We conducted an open labelled pilot study of 10 refractory venous ulcers of large size to determine the effect of non contact ultrasound on wound closure, bacterial counts, expression of inflammatory cytokines and pain reduction. We lacked a sham control group but we compared the baseline and end of treatment assessments and noted the differences. We found a significant reduction in wound area (P = 0.0039) over the 4-week treatment period. We also found a decline in individual and total bacterial counts; however, these differences were not significant. For all patients, there was also a trend toward reduced inflammatory cytokine expression compared with baseline levels; however, this reduction did not reach statistical significance. Interestingly, there was a correlation between healing and change in cytokine expression, which showed statistically significance for tumour necrosis factor (TNF)-alphaP = 0.0395, IL-1a P = 0.0351, IL-6 P = 0.0508, IL-8 P = 0.0990. Pain as measured by the visual analogue scale (VAS) was reduced from 4 at the baseline to 2.7 by the end of the study. In conclusion, we found that patients treated with ultrasound therapy and compression therapy show clinical improvement over the course of 4 weeks and had a decrease in inflammatory cytokines, bacterial counts and pain. PMID- 22296348 TI - Piper betel Linn (betel vine), the maligned Southeast Asian medicinal plant possesses cancer preventive effects: time to reconsider the wronged opinion. AB - Since antiquity, Piper betel Linn (betel vine; family Piperaceae) has been an important medicinal agent in the various traditional and folk systems of medicine in Southeast Asia countries. The leaves are the most valued plant part and in the past were routinely used as a chewing agent to prevent halitosis. The leaves are also supposed to harden the gum, conserve the teeth and to prevent indigestion, bronchitis, constipation, congestion, coughs and asthma. Innumerable scientific studies have validated the ethnomedicinal claims. Betel leaves are an integral component of the betel quid that consists of areca nut (Areca catechu Linn.), tobacco (Nicotiana tabacum L) and slaked lime; a highly abused agent with carcinogenic properties. Regular chewing of betel quid is associated mainly with oral cancer and detail studies with individual constituents of the quid have shown that both tobacco and areca nut are carcinogenic, while slaked lime is shown to promote the process of carcinogenesis. However unlike other constituents of the betel quid, the betel leaves devoid carcinogenic effects and on the contrary possesses cancer preventive effects including against the carcinogens present in tobacco. This review for the first time provides information on cancer preventive effects and also addresses the various mechanisms which might be involved. PMID- 22296349 TI - Radiation oncology facilities in Turkey: current status and future perspectives. AB - BACKGROUND AND PURPOSE: An analysis of the current radiotherapy status in Turkey was conducted to establish a comprehensive baseline. Turkey's future demand analysis in view of international benchmarks was conducted. Moreover, the ministerial plans are shared to present an example for making a comprehensive planning in developing countries. METHODS: The data from all radiotherapy centers in Turkey was collected through a survey and cross-checked with primary research and government data. Survey covered the status of radiotherapy centers in terms of major equipment and personnel. Data regarding manpower currently working is obtained from relevant academic centers and occupational associations. RESULTS: The latest ministerial registry data demonstrated 150,000 new cancer cases each year with 400,000 patients living with cancer in Turkey. Around 100,000 patients are estimated to need radiotherapy each year--a figure expected to reach around 170,000 by 2023. The current numbers for radiotherapy centers, megavoltage equipment, radiation oncologists, medical physicists and radiotherapy technicians are 90, 186, 446, 130 and 600 respectively. By 2023, Turkey will need around 680 radiation oncologists, 624 medical physicists, 2,650 radiotherapy technicians and 379 megavoltage machines. CONCLUSION: Turkey faces a slight oversupply of radiation oncologists in contrast to undersupply in megavoltage machines and other personnel. Careful planning is required to allocate limited resources. The purchase of the equipment and employment policies should be structured as part of national cancer control program. PMID- 22296350 TI - Relationship between CYP1A1 genetic polymorphisms and renal cancer in China. AB - AIM: To study the potential role of cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) polymorphisms in the risk of renal cell cancer in Chinese. METHODS: A total of 181 pathologically-proven renal cancers and 350 controls from the second Xiangya Hospital in Changsha were collected during the period from May 2007 to December 2010. CYP1A1 genetic polymorphisms were genotyped using PCRRFLP. Unconditional logistic regression analysis was performed to analyze their relationship with risk of RCC. RESULTS: Individuals with Val/Val genotypes had a significantly increased risk of RCC compared those with CYP1A1 IIe/IIe (OR=1.69, 95%CI=1.03-2.85). We also found CYP1A1 Wt/Vt and Vt/Vt to confer a significantly greater risk than CYP1A1 Wt/Wt (Wt/Vt: OR=2.14, 95%CI=1.24-3.45; Vt/Vt: OR=1.78, 95%CI=1.31-3.96). In smokers, a high increase risk of RCC was observed in those with CYP1A1 Val allele and Vt allele (Val allele: OR=2.13, 95%CI=1.40-2.57; Vt allele: OR=3.75, 95%CI=2.43-6.79), but no other significant interactions were found. CONCLUSION: Our study found suggestive evidence that CYP1A1 polymorphisms may play an important role in the etiology of RCC. Cigarette smoking may increase the susceptibility to RCC carcinogenesis in individuals with a high-risk genotype. PMID- 22296351 TI - Fat intake and its relationship with pre- and post-menopausal breast cancer risk: a case-control study in Malaysia. AB - BACKGROUND: Fat intake has been shown to play a role in the etiology of breast cancer, but the findings have been inconsistent. OBJECTIVE: To assess the association of premenopausal and postmenopausal breast cancer risk with fat and fat subtypes intake. METHODOLOGY: This is a population based case-control study conducted in Kuala Lumpur, Malaysia from January 2006 to December 2007. Food intake pattern was collected from 382 breast cancer patients and 382 control group via an interviewer-administered food frequency questionnaire. Logistic regression was used to compute odds ratios (OR) with 95% confidence intervals (CI) and a broad range of potential confounders was included in analysis. RESULTS: This study showed that both premenopausal and postmenopausal breast cancer risk did not increase significantly with greater intake of total fat [quartile (Q) 4 versus Q1 OR=0.76, 95% CI, 0.23-2.45 and OR=1.36, 95% CI, 0.30 3.12], saturated fat (ORQ4 to Q1=1.43, 95% CI, 0.51-3.98 and ORQ4 to Q1=1.75, 95% CI, 0.62-3.40), monounsaturated fat (ORQ4 to Q1=0.96, 95% CI, 0.34-1.72 and ORQ4 to Q1=1.74, 95% CI, 0.22-2.79), polyunsaturated fat (ORQ4 to Q1=0.64, 95% CI, 0.23-1.73 and ORQ4 to Q1=0.74, 95% CI, 0.39-1.81), n-3 polyunsaturated fat (ORQ4 to Q1=1.10, 95% CI, 0.49-2.48 and ORQ4 to Q1=0.78, 95% CI, 0.28-2.18), n-6 polyunsaturated fat (ORQ4 to Q1=0.67, 95% CI, 0.24-1.84 and ORQ4 to Q1=0.71, 95% CI, 0.29-1.04) or energy intake (ORQ4 to Q1=1.52, 95% CI, 0.68-3.38 and ORQ4 to Q1=2.21, 95% CI, 0.93-3.36). CONCLUSION: Total fat and fat subtypes were not associated with pre- and postmenopausal breast cancer risk after controlling for age, other breast cancer risk factors and energy intake. Despite the lack of association, the effects of total fat and fat subtypes intake during premenopausal years towards postmenopausal breast cancer risk still warrant investigation. PMID- 22296352 TI - Green tea drinking habits and gastric cancer in southwest China. AB - AIM: The purpose of this study was to investigate relationships between green tea consumption and gastric cancer development. METHODS: A population-based case control study including 200 cases and 200 controls was conducted in the southwest area of China from May 2010 to February 2011. A self-designed questionnaire was used to collect data on factors influencing gastric cancer development, including tea drinking, conditional logistic regression being used to calculate odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs). RESULTS: Cases with higher economic status had a reduced risk of gastric cancer, while those with cancer family history, drinking and smoking showed increased risk. Hot and very hot tea temperature was significantly related to high risk of gastric cancer with ORs (95%Cl) of 1.82 (1.03-3.52) and 3.07 (1.78-7.36), respectively. Further analysis indicated elevated risk of gastric cancer in former drinkers, former smokers and current drinkers when the measured tea temperature was hot. CONCLUSION: Drinking tea at high temperature increases the gastric cancer risk, especially in drinkers and smokers. PMID- 22296353 TI - Clinical features and molecular phenotypes of breast cancer in patients with type 2 diabetes mellitus. AB - OBJECTIVE: To investigate the clinical features, molecular phenotypes and clinical prognosis of breast cancer patients with type-2 diabetes mellitus, thereby providing a basis for individualized therapy of breast cancer. METHODS: 105 breast cancer patients with type-2 diabetes mellitus (DM) presenting from January 2005 to December 2010 were enrolled in this study. 200 breast cancer non diabetic patients in the same period were randomly selected as the control group. The clinical data of DM group and control group were retrospectively analyzed. The SPSS12.0 software was used for statistics and survival analysis. RESULTS: The mean age of the patients in DM group were of 57.2?11.8 years, which was older compared with the control group. The percentage of postmenopausal patients was 71.4% and the ratio of grade II+III was 98.8%, which was higher than the control group. The neoadjuvant chemotherapy response rate of DM group was 67.5%, which was lower than control group. The patients in DM group had later clinical stage and more lymph metastasis. The proportion of advanced breast cancer was 68.57% and the ratio of lymph node metastasis was 66.01%. All the difference was significant (P<0.05). But there was no significant difference in tumor size and molecular phenotype between the diabetic group with breast cancer and the control group. Disease-free survival and overall survival rates of DM group were 80.2% and 84.2%, which were worse than those in the control group. All the differences were significant (P<0.05). After excluding the patients with other causes of death, results of overall survival still showed worse in DM group, but the difference was not statistically significant (P>0.05). Serum insulin at fasting and two hours postprandial were higher than normal value in DM group, but serum insulin levels in the control group changed in the normal range. CONCLUSION: There were older patients, higher proportion of high pathological grade, more lymph node metastasis, later clinical stages in the diabetic group with breast cancer. Breast cancer patients with type-2 diabetes mellitus were at risk of a poor prognosis. Hyperinsulinemia may be the real cause of poor prognosis in breast cancer patients with type-2 diabetes. PMID- 22296354 TI - Hot beverage and food intake and esophageal cancer in southern China. AB - AIM: Hot beverage and food intake may be associated with increased risks of esophageal cancer. In this study, we analyzed data from two hospital based case control studies to examine this question. METHODS: A structured questionnaire was used to collect data on potential risk factors of esophageal cancer from 213 cases and 213 controls in southern of China from Jan. 2007 to Dec. 2010. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional multivariable adjusted logistic regression, adjusting for confounders. RESULTS: Those who consumed hot and very hot beverages demonstrated significantly increased risk of esophageal cancer (OR=4.13, 95% CI: 2.13-8.05; OR=8.55, 95% CI: 3.67-20.9, respectively), related to increasing temperature. A high frequency of barbecued and fried food was also revealed to elevate risk of esophageal cancer (OR=3.44, 95% CI: 1.12-8.34, p for trend 0.034; OR=2.39, 95% CI: 1.25-6.32, p for trend 0.035). Furthermore, we found evidence for an association with a fast eating habit in our Chinese (OR=4.76, 95% CI: 2.12-7.74). CONCLUSION: This study found hot beverage and high-temperature cooking methods might greatly increase the risk of esophageal cancer. Further studies in Chinese populations with larger sample size are warranted. PMID- 22296355 TI - Smokers can quit regardless of motivation stage in a worksite smoking cessation programme in Malaysia. AB - BACKGROUND: There is an unclear relationship between smoker's early motivation and success rates. Here we aimed to explore the correlates of motivation and smoking abstinence and relapse in worksite smoking cessation programmes. METHODS: This prospective cohort study involved employees from two major public universities in Malaysia. Participants were actively recruited into a smoking cessation programme. At the start of treatment, participants were administered a questionnaire on sociodemographic variables, smoking habits and 'stage of change'. Behaviour therapy with free nicotine replacement therapy (NRT) was given as treatment for two months. A similar stage of change questionnaire was given at six months, and their smoking status was determined. RESULTS: There were 185 smokers from both Universities, who joined the programme. At six months, 24 smokers reported sustained abstinence while the others had relapsed. Prior to the programme, the majority of smokers were seriously planning on quitting (59.5%- preparation stage), but over a third had no plans to quit (35.5%--contemplation stage). There was no significant difference noted in changes of motivation stage among the relapsers and the non quitters. In addition, logistic regression showed that sustained abstinence was not predicted by pre-session motivation stage, but this did predict higher relapse for the participants, compared to those in the preparation stage. CONCLUSION: It is possible to help smokers in the lower motivation groups to quit, provided extra caution is taken to prevent relapse. Healthcare providers' recruitment strategies for cessation programmes should thus encompass smokers in all motivation stages. PMID- 22296356 TI - Cyclin D1 amplification in tongue and cheek squamous cell carcinoma. AB - INTRODUCTION: Several molecular markers have been studied for their usefulness as prognostic markers in oral squamous cell carcinoma (OSCC). One such molecular marker is cyclin D1 which is a proto-oncogene located on 11q13 in humans. OBJECTIVE: To explore the feasibility of using cyclin D1 as a prognostic marker in tongue and cheek SCC by the fluorescent-in-situ hybridization (FISH) method. METHODS: Fifty paraffin-embedded samples (25 each of cheek and tongue SCCs) were obtained from the archives of the Oral Pathology Diagnostic Laboratory. Sociodemographic data, histopathologic diagnoses, lymph node status and survival data were obtained from the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS)coordinated by the Oral Cancer Research and Coordinating Centre (OCRCC), University of Malaya. The FISH technique was used to detect the amplification of cyclin D1 using the Vysis protocol. Statistical correlations of cyclin D1 with site and lymph node status were analyzed using the Fisher exact test. Kaplan Meier and Log Rank (Mantel-Cox) test were used to analyze cyclin D1 amplification and median survival time. RESULTS: Positive amplification of cyclin D1 was detected in 72% (36) of OSCCs. Detection of positive amplification for cyclin D1 was observed in 88% (22) and 56% (14) of the tongue and cheek tumors, respectively, where the difference was statistically significant (P=0.012). Lymph node metastasis of cheek SCCs showed a trend towards a significant association (P= 0.098) with cyclin D1 amplification whereas the lymph node metastasis of tongue SCC was clearly not significant (P=0.593).There was a statistically significant correlation between cyclin D1 positivity and survival rate (P=0.009) for overall SCC cases and (P<0.001) for cheek SCC cases. CONCLUSION: The present study found that cyclin D1 amplification may differ in different subsites of OSCC (tongue vs cheek) and its positive amplification implies an overall poor survival in OSCCs, particularly those arising in cheeks. PMID- 22296357 TI - Hepatitis B vaccination and liver cancer mortality reduction in Korean children and adolescents. AB - Liver cancer is one of the three most common causes of cancer mortality in the world and it is closely related to chronic hepatitis B viral (HBV) infection in Korea. The decline of HBV prevalence for the last two decades in Korea might be partly due to the HBV vaccination, which was implemented as a national program starting in 1995. The aim of this study was to assess the period effect of the national HBV vaccination on liver cancer mortality in a young population. We compared age-specific mortality rates of liver cancer before and after the national vaccination program in the Korean population under the age of 20. To reduce year-to-year fluctuations in mortality, calendar years and age groups were divided into 4-year strata and the mortality rates were calculated for each stratum. Period effects of the national vaccination program were analyzed using age-period-cohort modeling. A total of 370 liver cancer mortality cases were identified during the period from 1991 to 2006. The period effect of the national vaccination program for the period 2002-2006 had a significantly reduced liver cancer mortality rate when compared to the period 1991-1994 when the national vaccination program was not implemented (RR 0.30, 95% CI 0.21~0.44). After implementation of the national vaccination program, HBV prevalence in Korean declined from 6~8% to 2~3%. This study demonstrates that the national vaccination program has contributed to the reduction of liver cancer mortality beyond just a natural decrease in Korean children and adolescents. PMID- 22296358 TI - Trends in liver cancer incidence between 1985 and 2009, Khon Kaen, Thailand: cholangiocarcinoma. AB - BACKGROUND: The Khon Kaen Cancer Registry (KKCR), having both hospital and population-based registration, was established in 1984 at the Faculty of Medicine, Khon Kaen University. Liver cancer is the most frequent malignancy among Thais from northeastern Thailand, but there has hitherto been no assessment of trends over time. OBJECTIVE: To perform a statistical assessment of the incidence trends between 1985 and 2009 of liver cancer, specifically focusing on cholangiocarcinoma (CHCA). METHODS: Cases of CHCA, registered between 1985 and 2009, were retrieved from the KKCR and all those with a specific ICD-O-3rd diagnosis with a coding of C22.1, C24.0, C24.8 and C24.9 were selected. Incidence trends were calculated using the generalized linear model method (GLM), which generates incidence rate based logarithms. Jointpoint analysis was used to identify the best fitting model. RESULTS: Of the 18,589 cases of liver cancer 42% (7,859) were hepatocellular carcinoma and 58% (10,731) were CHCA. Among persons with CHCA, males were affected two times more frequently than females. Three quarters of the cases were between 55 and 69 years of age. Morphology verified through a cytological or histological examination of tissue from the primary site (%MV) was only 10.8 % (1,141). The respective overall Age Standardized Rate (ASR) for CHCA from 1985 to 2009 was 16.8 to 62.0 per 100,000 among males and 4.8 to 25.6 per 100,000 among females. The respective, overall, ASR of CHCA among males vs. females was 44.3 per 100,000 (95% CI: 38.9 to 49.7) vs. 17.6 (95% CI: 14.5 to 20.7). Among males vs. females, the respective incidence from 1990 to 2009 has been significantly decreasing by -0.7% per year (Annual Percent Change, APC: 0.7%, 95%CI: -2.1% to +0.8%) vs. -0.4% per year (APC: -0.4%, 95% CI: -2.1% to +1.4%). CONCLUSIONS: The rate increase in the first 5 to 6 years may be due to improved completeness of the registry, since in the subsequent 10 to 12 years there is a rather stable rate. It may be, however, that the recent decline in incidence represents a real fall in risk. PMID- 22296359 TI - Childhood cancer incidence and survival 2003-2005, Thailand: study from the Thai Pediatric Oncology Group. AB - BACKGROUND: Previous population-based incidences of childhood cancer in Thailand were achieved by extrapolating from data limited to a small number of cancer registries, not from the whole country. In addition, survival of childhood cancer patients is often described in specialized hospitals and/or institutions, but not in the general population. METHODS: All children aged 0-15 years who were newly diagnosed as having cancer were registered from 18 treatment centers during 2003 5 and classified into 12 diagnostic groups according to the International Classification of Childhood Cancer. Incidences were calculated by a standard method and survival was investigated using the ThaiPOG (Thai Pediatric Oncology Group) population-based registration data. Overall survival was calculated by the Kaplan Meier method. RESULTS: In the study period (2003-5) 2,792 newly diagnosed cases of childhood cancer were registered, with mean and median ages of 6.5 (SD=0.13) and 5.0 (0-14) years, respectively. The age-peak was between 1 and 4 years and the age-standardized rate (ASR) was 74.9 per million. Leukemia was the most common cancer (N=1421, ASR 38.1) followed by lymphoma (N=266, ASR 6.4) and neoplasms of the central nervous system (CNS, N=246, ASR 6.3). The follow-up duration totaled 101,250 months. The death rate was 1.11 per 100 person-months (95%CI: 1.02 -1.20). The 5-year overall survival was 54.9% (95%CI: 53.0%-56.9%) for all cancers. The respective, 5-year overall survival for (1) acute lymphoblastic leukemia (ALL), (2) acute non-lymphoblastic leukemia (ANLL), (3) lymphoma, (4) retinoblastoma, (5) renal tumors, (6) liver tumors, (7) germ cell tumors, (8) CNS tumors, (9) neuroblastoma, (10) soft tissue tumors and (11) bone tumors were (1) 64.5%, (2) 35.1%, (3) 59.5%, (4) 73.1%, (5) 70.4%, (6) 44.5%, (7) 70.6%, (8) 41.7%, (9) 33.6%, (10) 50.1%, and (11) 33.7%. CONCLUSIONS: The incidence of childhood cancer is lower than in western countries. Respective overall survival for ALL, lymphoma, renal tumors, liver tumors, retinoblastoma, soft tissue tumors is lower than those reported in developed countries while for CNS tumors, neuroblastoma and germ cell tumors the figures are comparable. PMID- 22296360 TI - Glutathione S-transferase M1 and T1 status and the risk of laryngeal cancer: a meta-analysis. AB - BACKGROUND: Polymorphic variations in GSTM1 and GSTT1 have been implicated as risk factors for various cancers. A number of studies conducted to assess their association with susceptibility to laryngeal carcinomas have yielded inconsistent and inconclusive results. In the present study, the possible association of laryngeal cancer risk with GSTM1 and GSTT1 null genotypes was explored by a meta analysis. METHOD: A meta-analysis was carried out on case-control studies collected from the literature. The pooled odds ratio (OR) and presence of publication bias in those studies were evaluated. RESULTS: A total of 20 studies concerning laryngeal cancer were identified. The results showed that the pooled OR was 1.22 (95% CI 1.03 1.43) for the GSTM1 polymorphism while for GSTT1 polymorphism, the pooled OR was 1.23 (95% CI 0.96-1.58). No evidence of publication bias was detected among the included studies. CONCLUSION: The results suggest that the GSTM1 deficiency significantly increases susceptibility to laryngeal cancer whereas GSTT1 null genotype might not be a risk factor. PMID- 22296361 TI - MTHFR gene polymorphisms and bladder cancer susceptibility: a meta-analysis including race, smoking status and tumour stage. AB - Epidemiological studies have investigated that functional polymorphisms in the methylene-tetrahydrofolate reductase (MTHFR) gene may play an essential role in bladder carcinogenesis, but the numerous published studies have reported inconclusive results. The objective of the current study was to conduct an updated analysis in order to investigate the association between polymorphisms in the MTHFR gene and risk of bladder cancer. We searched the Pubmed database for all articles published up to March 31, 2011 that addressed bladder cancer and polymorphisms and variants or mutations of MTHFR for analysis using statistical software. Results for two polymorphisms (C677T and A1298C) in 27 case-control were studies from 15 articles indicated individuals carrying the 677T allele (TC or TT+TC) to have a reduction to a 29% or 21% compared to the wild genotype (CC) in mixed populations (OR: 0.71, 95%CI: 0.55-0.93 or OR: 0.79, 95%CI: 0.64-0.97, respectively) and it is shown that there is significant positive associations between A1298C polymorphism and bladder cancer in Africans (OR: 1.24, 95%CI: 1.02 1.52 for C vs.A; OR: 1.35, 95%CI: 1.10-1.66 for CA vs. AA; OR: 1.29, 95%CI: 1.08 1.55 for CC+CA vs. AA). However, no significant relationship was found in two polymorphisms in the stratified analysis by smoking status. Interestingly, individuals carrying the 677T allele (TT+TC) demonstrated a higher percentage of invasive than superficial cases (OR: 1.38, 95%CI: 1.13-1.69). The results from the current update analysis suggest that C677T and A1298C polymorphisms in the MTHFR gene are associated with bladder cancer risk and prognosis. Further evaluation based on more studies with larger groups of patients are now required. PMID- 22296362 TI - A clinical study on safety and efficacy of Aidi injection combined with chemotherapy. AB - OBJECTIVE: To observe the efficacy, side effects and impact on the quality of life of Aidi Injection combined with leucovorin calcium/5 fluorouracil/oxaliplatin (FOLFOX4 regimen) in the treatment of advanced colorectal cancer patients. METHODS: A consecutive cohort of 100 patients were divided into two groups: the experimental group was treated with Aidi injection and FOLFOX4 while the control group was only administered FOLFOX4. After more than two courses of treatment, efficacy, quality of life and side effects were evaluated. RESULTS: The response rate of experimental group was not significantly different with that of control group (P>0.05), but differences were significant in clinical benefit response and KPS score. Iin addition, gastrointestinal reaction and the incidence of leukopenia were lower than that of control group (P<0.05). CONCLUSIONS: Aidi injection combined with FOLFOX4 is associated with reduced toxicity of chemotherapy, enhanced clinical benefit response and improved quality of life of patients with advanced colorectal cancer. Aidi injection deserves to be further investigated by randomized control clinical trails. PMID- 22296363 TI - XRCC1 Arg399Gln gene polymorphism and breast cancer risk: a meta-analysis based on case-control studies. AB - BACKGROUND: The Arg399Gln polymorphism in the XRCC1 DNA repair gene is likely to be involved with the development of breast cancer (BC). However, there have been inconsistent reports of association. The objective of this study was to systematically evaluate the published papers. METHODS: We performed a meta analysis of 44 published case-control studies fitting our eligibility criteria. These studies involved XRCC1 Arg399Gln polymorphisms in 20,841 BC cases and 22,688 controls in dominant (GlnGln+ArgGln vs. ArgArg), recessive (GlnGln vs. ArgGln+ArgArg), and co-dominant (GlnGln vs. ArgArg) inheritance models. Analyses of Asian, African and Caucasian ethnic subgroups was also conducted. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. RESULTS: Our overall analyses indicated Arg399Gln to be associated with a trend of increased BC risk when using recessive (OR=1.15, 95%CI: 1.05 1.27), and co-dominant models (OR=1.15, 95%CI: 1.04-1.27) to analyze the data. In ethnic subgroups, Arg399Gln significantly increased BC risk in Asians (OR=1.54, 95%CI: 1.18-2.01) when using recessive model analysis, in Africans (OR=1.30, 95%CI: 1.07-1.60) when using dominant model analysis, and in Asians (OR=1.50, 95%CI: 1.15-1.97) and Africans (OR=1.80, 95%CI: 1.08-3.02) when using the co dominant model analysis. CONCLUSIONS: From our meta-analysis of data from 44 publications, we conclude that XRCC1 Arg399Gln allele is a risk factor for the development breast cancer, especially among Asian and African populations. PMID- 22296364 TI - A retrospective analysis of thyroid cancer in China. AB - BACKGROUND: Thyroid nodules are a common clinical problem that require close attention to determine the risk of malignancy. This study was designed to investigate the diagnostic values of pathological characteristics, ultrasonographically-detected calcification, and serum TSH levels in thyroid cancer in Han Chinese. METHODS: A retrospective analysis was carried out using 1,685 patients with thyroid cancer or benign nodules, who had undergone thyroidectomy between 2008 and 2009 in our hospital. RESULTS: Among the 1,685 cases, 222 had thyroid carcinomas and, of those, 113 (50.9%) developed different benign thyroid diseases. The frequency of thyroid cancer showed a progressive decrease from the younger to the older patients. The frequency of malignancy was closely related to the level of calcification, with the lowest frequency occurring in patients with no calcification and the highest in those with micro calcification. The frequency of malignancy was also closely related to serum TSH levels, with the lowest occurring in patients with TSH levels <0.40 uIU/mL, and the highest with >1.34 uIU/mL; in addition, <4.00 uIU/mL TSH showed a progressive increase from the lower to the upper of normal range. CONCLUSIONS: Thyroid malignancies often coexist with benign thyroid disease. Age, TSH levels, and calcification of the nodules are predictors of malignancy. PMID- 22296365 TI - Anticancer effects of Huaier are associated with down-regulation of P53. AB - This study was designed to explore the mechanism of Huaier anticancer effects on experimental hepatocellular cancer (HCC) development. Seventy five rats were divided into 5 groups, administered N-nitrosodiethylamine (groups B, C, D and E) or natural saline (group A). Rats in group C and E were also given Huaier. At the 15 week sacrifice point, the HCC incidence of group C was lower than group correlating with serum AFP. The serum ALT concentration (98.9% greater) and P53 mRNA levels (23.2%) were higher in Group B than group C. Longer term survival rates between group D and E were not significantly different. Huaier can protect liver from chemical injury and furthermore HCC development, possibly with involvement of down-regulation of P53. PMID- 22296366 TI - A qualitative study of Japanese patients' perspectives on post-treatment care for gynecological cancer. AB - The perspectives of cancer patients are important for designing a medically and economically effective follow-up program to help in the rapid recovery of patients. However, research focusing on the perspectives of Japanese gynecological cancer patients on follow-up programs is extremely scarce. In this study, we explored the perspectives and expectations of Japanese gynecological cancer patients with regard to post-treatment follow-up. Twenty-eight patients recruited through a gynecological cancer support group were included in focus groups 1-10 years post-treatment. Participants' accounts related to their perspectives on follow-up were coded and grouped into themes according to commonalities and differences. Seven themes emerged as follows: (1) living with uncertainty, (2) monitoring recurrence, (3) test content and frequency, (4) coping with "another illness", (5) provider communication and attitude, (6) holistic care, and (7) compromising with the reality of changed body. While these Japanese gynecological patients regarded follow-up as an opportunity for reassurance, they also wanted treatment for adverse effects and the opportunity to discuss their concerns. On the basis of the study findings, we conclude that during follow-up after cancer treatment, Japanese gynecological cancer patients not only prioritize recurrence management of cancer but also place a significant amount of importance on the management of symptoms and doctor-patient communication. However, these expectations for communication and care are often unmet. Thus, there is a need to fulfill the gap between the current follow-up programs and patients' expectations by reviewing and changing the hospital's policy that mainly focuses on the detection of recurrent diseases. PMID- 22296367 TI - Inhibition of proliferation and induction of apoptosis by trimethoxyl stilbene (TMS) in a lung cancer cell line. AB - Trimethoxyl stilbene (TMS) is a derivative of resveratrol, a compound shown to inhibit development of a variety of tumor types. We aimed to evaluate the effect of TMS on cell proliferation and apoptosis in the A549 non-small cell lung cancer cell line. Growth inhibition rate and colony formation was measured and apoptosis was determined with Hoechst 33258 staining. Protein expression levels of caspase 3, STAT3, STAT5b, JAK2, NF-kappaB, and IkappaB were examined by Western blotting. Furthermore, localization of NF-kappaB protein was also explored. TMS inhibited proliferation (IC50 8.6 MUmol/L) and induced apoptosis of the cells in a concentration-dependent manner., also inducing apoptosis accompanied by up regulated expression and cleavage activation of caspase-3, up-regulation of IkappaB and down-regulation of NFkappaB, STAT3, STAT5b, and JAK2 signal transduction. TMS has potential as a new drug for treatment of non-small cell lung cancer patients with anti-proliferation and apoptosis inducing effect of TMS to A549 cells apparently related to its inhibitory effect on STATs and NF-kappaB signal transduction. Up-regulation of caspase-3 further supports the potential clinical use of TMS for the treatment of non-small cell lung adenocarcinoma. PMID- 22296368 TI - Pancreatic cancer mortality and misclassification--bayesian analysis. AB - BACKGROUND: Pancreatic cancer is a fatal cancer with a 5-year survival of only about 4% for all tumors. Mortality is a familiar projection to address the burden of cancers, but according to the Iranian death registry, about 20% of death statistics are still recorded in misclassified categories. The aim of this study was to estimate pancreatic cancer mortality for Iranian population, using a bayesian approach in order to revise this misclassification. METHODS: National Death Statistics reported by the Ministry of Health from 1999 to 2004, stratified by age group, sex and cause of death, were the basis for this analysis. Pancreas cancer [ICD-10; 25] were expressed as the annual mortality rates/100,000, overall, by sex and by age group (<50 and >=50 years of age) and age standardized rate (ASR). The bayesian approach to correct and account for misclassification effects in Poisson count regression was employed with a beta prior to estimate the mortality rate by age and sex group. RESULTS: According to the bayesian analysis, there were between 20 to 30 percent underreported mortality records in deaths due to pancreatic cancer and the rate decreased slightly during the years of the study. CONCLUSION: Our findings suggest a substantial undercount of pancreatic cancer mortality in the Iranian population. Therefore policy makers who determine research and treatment priorities should note these underreported data for death rates. PMID- 22296369 TI - Effects of the MTHFR C677T polymorphism on prostate specific antigen and prostate cancer. AB - Prostate cancer is the most common malignancy and the second leading cause of cancer related deaths among men in many countries. Serum levels of prostate spesific antigen (PSA) have attracted attention for prediction purposes. The methylenetetrahydrofolate reductase (MTHFR) gene play a critical role in cancer development, but its potential impact on prostate cancer has not been well studied. The C677T variant lies in exon 4 at the folate binding site of the MTHFR gene and results in substitution of an alanine by a valine residue. The present study was carried out 55 cases with prostate cancer and 50 healthy men. Polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and agarose gel electrophoresis techniques were employed to determine MTHFR C677T mutation. The frequencies of the CT genotype (p= 0.025) and T allele (p= 0.023) was found to be higher in control subjects when compared with patients group. No statistical difference was found between the alleles of MTHFR and PSA levels after (PSA-BT)/ before (PSA-AT) antiandrogen treatment or tumor stages. We suggest that the heterozygote CT genotype and the 677T allele of the MTHFR polymorphism might be associated with an decreased prostate cancer risk. PMID- 22296370 TI - Null genotype of GSTT1 contributes to colorectal cancer risk in Asian populations: evidence from a meta-analysis. AB - BACKGROUND/AIMS: Studies of associations between genetic polymorphism of glutathione S-transferase T1(GSTT1) and risk of colorectal cancer (CRC) in Asian populations have reported controversial results. Thus, a meta-analysis was performed to clarify the effects of GSTT1 polymorphism on the risk of developing colorectal cancer. METHODS: A literature search of PubMed and EMBASE up to June 7, 2011 was conducted and 13 eligible papers were finally selected, involving totals of 4,832 CRC cases and 7,045 controls. Subgroup analyses were performed according to the sample size and the research design with the software programs Review Manager (version 5.0.10) and STATA (version 9.2). RESULTS: Analyses of all relevant studies showed an increased CRC risk was significantly associated with the null genotypes of GSTT1 (OR=1.09, 95%CI=1.01-1.17, POR=0.027; I2=40.2%). Besides, a more obvious association was observed after heterogeneity was eliminated (OR=1.13, 95%CI 1.04-1.23, POR=0.002; I2=0.0%). Subgroup analyses and sensitivity analysis further identified an association in Asians. CONCLUSIONS: This meta-analysis demonstrated the GSTT1 null genotype to be associated with an increased risk of CRC in Asian populations. PMID- 22296371 TI - Loss of runt-related transcription factor 3 expression associated with human hepatocellular carcinoma progression and prognosis. AB - BACKGROUND: This study aimed to evaluate the expression level of runt-related transcription factor 3 (RUNX3) in human primary hepatocellular carcinomas (HCCs) and its relationship with the clinic pathological features. METHODS: RUNX3 expression was analyzed by real-time fluorescent quantitative PCR, immunohistochemistry and Western blotting in HCC cells and tissues. RESULTS: RUNX3 RNA and protein expression was decreased in HCC tissues compared with the adjacent normal tissues (P< 0.001), mRNA frequently being down-regulated in HCC cell lines (66.67%, 4/6). Low expression of RUNX3 showed a significant correlation with cirrhosis (P = 0.028), histologic type (P = 0.000) and lymph node metastasis (P= 0.004). CONCLUSION: RUNX3 expression is deleted or decreased in HCCs and cell lines, in association with progression and prognosis. PMID- 22296372 TI - Influence of MDR1 gene codon 3435 polymorphisms on outcome of platinum-based chemotherapy for advanced non small cell lung cancer. AB - OBJECTIVE: To evaluate the influence of multi-drug resistance 1 (MDR1) gene codon 3435 polymorphisms on response to platinum-based chemotherapeutic regimens for advanced non small cell lung cancer (NSCLC). METHODS: Responses and overall survival were evaluated in a series of patients presenting between March 1, 2005 and December 31, 2010. MDR1 gene C3435T polymorphisms were genotyped using peripheral blood with real time polymerase chain reaction (RT-PCR) and relationships between the MDR1 C3435T genetic polymorphism and response rate of chemotherapy were analyzed by SPSS 13.0. RESULTS: Overall response to chemotherapy in the eligible 103 patients was 21.4%. Patients with C/C genotype in MDR1 codon 3435 had a significantly higher response rate (24.5%) than those for C/T(19.0%) and T/T(12.5%) (P<0.05). The overall median survival time (MST) of patients was 19 months, values with C/C, C/T and T/T genotype were 21, 15.5 and 17 months, respectively (P=0.487). CONCLUSION: Our research suggested that patents with the C/C genotype in MDR1 codon 3435 could be more sensitive to platinum-based chemotherapy than patients with C/T and T/T; however, no significant difference was found between overall survival and MDR1 codon 3435 genetic polymorphisms. PMID- 22296373 TI - Age characteristics of incidences of prevalent cancers in the Aral Sea area of Kazakhstan. AB - The aim of the research was to examine age-specific features of incidence of cancer of the esophagus, lung, stomach, breast, cervix and thyroid gland in the Aral Sea area in Kazakhstan. A retrospective study of 11 years (1999-2009) was conducted using descriptive and analytical methods with calculated age incidence rates. The average age of patients with esophageal cancer and lung cancer had a tendency for increase with "aging", while in other cases "juvenation" was noted. The peak incidence of malignant tumors in general, and in the studied forms of cancer was found at 70 years of age or older, except for breast cancer and cervical cancer, where the peak incidence was found at 60-69 years. Trends in age varied incidence rates had different tendencies in particular organ sites. PMID- 22296374 TI - Trends of prevalent cancer incidences in the Aral-Syr Darya ecological area of Kazakhstan. AB - The aim of this research was to examine the incidence of major forms of cancer in the Aral-Syr Darya ecological area of Kazakhstan. The present retrospective study of 11 years (1999-2009) was therefore conducted using descriptive and analytical methods. Incidence rates (crude and standardized) of 11 leading cancer sites were calculated and trends determined. The result of analysis demonstrated the most common neoplams in the study region to be esophageal cancer, carcinoma of lung, stomach cancer, and breast cancer. Trends in incidence of cancers under study were different, the most marked reduction in cancer of esophagus is established (T=-6.1%) and revealed the high increase in breast cancer (T=+6.7%). In the dynamics the trend of malignant disease in general tended to decrease (T=-0.5%). PMID- 22296375 TI - Lung cancer in central Tunisia: epidemiology and clinicopathological features. AB - Lung cancer is the most common cancer worldwide but data from Tunisia are limited. The aim of this research was to describe the epidemiology, pathology and clinical features of lung cancer in Central Tunisia. All lung cancer cases diagnosed during a 15-year period were analyzed based on the data of the Cancer Registry of the Center of Tunisia. Five-year age-specific rates, world age standardized rates (ASR), and annual percent change were calculated using annual data on population size and the estimated age structure. A total of 1,882 incident cases of lung cancer were registered (1,782 males, 100 females). The median age at diagnosis was 64 years for males and 61 years for females, with ASRs of 35.2 per 100,000 among males and 1.5 among females. Over time, there were significant decreasing trends by -6.5% (95% CI: -12.9%; -0.2%) for females and a stable incidence for males at an annual rate of +0.2% (95% CI: -1.6%; +1.8%). The predominant histological type was squamous cell carcinoma in males (36.9%) and adenocarcinoma in females (52%). During 2003-2007, adenocarcinoma became the most frequent (33.7%) followed by squamous cell carcinoma (30.3%) in males. The majority of tumor cases were diagnosed at advanced stages (79.9%). In conclusion, lung cancer has remained the most common cancer diagnosed at advanced stages among Tunisian men. Our findings justify the need to plan and develop effective programs aiming at the control and prevention of the spread of lung cancer in Tunisia. PMID- 22296376 TI - Reasons for clinical breast examination in women applying at a cancer screening center in Erzurum. AB - This study was conducted to investigate the reasons for application of women for Clinical Breast Examination (CBE). METHODS: This descriptive study involved 155 women who applied to Cancer Screening and Education Center of Numune Hospital, Erzurum, Turkey between December 1, 2008 and January 30, 2009. The data collection was performed by evaluation of demographic characteristics of the participants using a descriptive information form to identify the application reasons. RESULTS: The age range of the participants was 37-68 years (mean: 48.7 years). Of the participants, 43.9% applied for breast screening; 31.0%, for pathological changes in the breast; 17.4%, for breast check-up, and 7.7%, for concerns over familial risk. CONCLUSIONS: Most of the women (69.0%) applied to the center without any pathological changes in their breasts. PMID- 22296377 TI - Breast cancer risk factors in Turkey: a hospital-based case-control study. AB - BACKGROUND: Regional disparities in breast cancer (BC) outcomes have been reported in Turkey. METHODS: In a hospital-based case-control study in Sivas, Turkey, 172 patients with histologically confirmed BC were compared with 383 controls, recruited from visitors in various departments of the same hospital, who had not been previously diagnosed with BC. Information was collected from both groups using a questionnaire and logistic regression analysis was applied to assess associations between each risk factor and BC risk with adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In multivariable models, family history of BC (OR=4.67, 95% CI: 2.23-9.76), history of smoking (OR=1.75, 95% CI: 1.08-2.84), and higher education level (OR=2.88, 95% CI: 1.64 5.07) were the strongest predictors of BC in the study population. A separate analysis studying only postmenopausal women using hormone replacement therapy (HRT) (comparing duration of use, >36 months versus <=36 months, P<0.05) found that use of HRT was also a risk factor for BC. Duration of HRT use (P<0.05) was significantly associated with the elevated risk. On the other hand, certain factors such as first full-term pregnancy before age 30 (chi2=5.755 P<0.05) and higher parity (chi2=20.731, P<0.05) were found to be protective factors for BC. CONCLUSION: The findings of the present study indicate that family history of BC, history of smoking, education, and HRT are factors significantly associated with increased BC risk among Turkish women within the area of Central Anatolia, Turkey. PMID- 22296378 TI - Characteristics of hospital controls according to willingness to participate in a cancer genetic epidemiologic research in China. AB - OBJECTIVE: Studies on participants' willingness to be interviewed in-person and donate blood specimens for genetic cancer research are few and most have been conducted in Western countries. Little information exists about the willingness to participate in genetic cancer research in China. METHODS: In 2009-2010, 560 hospital controls, matched to incidence cases by age, gender and residency, were randomly selected from outpatients attending the Health Examination Centre at the China Medical University's teaching hospital in Northeast China. Demographic and lifestyle characteristics were measured using a validated questionnaire by face to-face interview and 5 ml blood samples were collected from consenting participants. A 7-point 'willingness to participate' scale was developed for use by the interviewer to record the levels of ease or difficulty experienced in recruiting each participant. The willingness to participate was compared between different subgroups of participants. RESULTS: The participation rate was 96.1% among the hospital controls. Characteristics associated with willingness to participate were age (<=60 years) and tertiary education. Weaker associations with gender and malignancies in first degree relatives were not statistically significant. The factors not strongly or significantly associated with willingness to participate were income, marital status, body mass index, smoking, passive smoking, alcohol consumption, tea drinking, or physical activity. CONCLUSION: This study suggests that while there is general acceptance of participation in genetic cancer epidemiologic research in China across subgroups of outpatient hospital controls, younger age and education are associated with increased willingness to participate, while lifestyle factors generally had little impact. PMID- 22296379 TI - XRCC1 polymorphisms and risk of nasopharyngeal carcinoma: a meta-analysis. AB - OBJECTIVE: Previous studies on the association between X-ray repair cross complementing protein 1 (XRCC1) polymorphisms and nasopharyngeal carcinoma (NPC) risk showed inconsistent results. The aim of this study was to evaluate the effects of XRCC1 variants on NPC risk. METHODS: A meta-analysis was performed with all eligible studies covering a total of 1,341 cases and 1,425 controls for the Arg194Trp polymorphism, 1,260 cases and 1,207 controls for the Arg280His polymorphism, and 1,644 cases and 1,678 controls for the Arg399Gln polymorphism. RESULTS: No associations was found between Arg194Trp and Arg280His polymorphisms with NPC risk under all contrast models (co-dominant, dominant, and recessive models). However a deleterious effect of the 399Gln genotype was observed under the co-dominant model (Gln/Gln versus Arg/Arg, OR = 1.30, 95% CI : 1.01-1.69, P = 0.04). Under the recessive model (Gln/Gln versus Arg/Arg+Arg/Gln), the P value was marginally significant (OR = 1.28, 95% CI : 1.00-1.65, P = 0.05). However, the effect of the 399Gln genotype on NPC became non-significant after excluding one study from the meta-analysis because of departure from Hardy-Weinberg equilibrium. CONCLUSIONS: No associations were found between Arg194Trp and Arg280His polymorphisms with NPC risk, whereas the Arg399Gln genotype was associated with increased risk. PMID- 22296380 TI - Quality of life among breast cancer patients in Yemen. AB - OBJECTIVE: The objective of this study is to determine the quality of life among breast cancer patients in Yemen based on socio-demographic and clinical characteristics. METHODOLOGY: This study was designed as a cross-sectional study. The data collected from 106 female breast cancer patients who were chosen for recruitment from the outpatient in National Oncology Centre (NOC), Sana'a, Yemen from November 2008 to June 2011. Questionnaires were distributed to the patients during their visit to the outpatient clinics in the center. The instrument of this study consists of two parts: Socio-demographic and the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire. Regarding data analysis, means and SD of subscales were evaluated for descriptive purpose. Analysis of variance (ANOVA) was performed to compare the three groups regarding QOL subscales. Whereas, independent t-test was performed for comparing two groups regarding QOL subscales. Multiple linear regression using backward analysis was performed to obtain the final model for each domain. The final model was chosen depending on R2 and the p value of the model. A p value less than 0.05 is considered statistically significant. RESULTS: A total number of 106 breast cancer patients were participated in this study. The majority of them were uneducated, unemployed with normal weight and had middle income (60.4%; 95.3%; 59.4%, 46.2%; respectively). As for clinical characteristics of the study participants; the majority of them had had no family history of breast cancer, have been diagnosed at least 2 years, were diagnosed at grade 3 and size of tumor greater than 2 cm (88.7%, 66.0%, 35.8%, 73.6%; respectively). The majority of them underwent mastectomy, radiotherapy, chemotherapy and tamoxifen therapy (85.8%, 63.2%, 94.3% and 62.3%; respectively). For univariate analysis, the present study has identified several factors includes family monthly income, BMI, educational status, years after diagnosis, histological grade radiotherapy and surgery that influence the QOL of breast cancer patients in Yemen. For multivariate analysis, years after diagnosis, family monthly income and radiotherapy were significantly associated with total QOL of the breast cancer patients (p=0.01, p=0.023, p=0.039; respectively). CONCLUSION: Family monthly income, BMI, educational status, years after diagnosis, histological grade radiotherapy and surgery were significantly influence the QOL of breast cancer patients in Yemen, in univariate analysis. For multivariate analysis, years after diagnosis, family monthly income and radiotherapy were significantly associated with total QOL of the breast cancer patients. PMID- 22296381 TI - No association between the CYP1B1 C4326G polymorphism and endometrial cancer risk: a meta-analysis. AB - PURPOSE: Any association between the CYP1B1 C4326G polymorphism and endometrial cancer risk remains inconclusive. In order to provide a more precise estimate, we performed the present meta-analysis. METHODS: We used fixed effect or random effect models to estimate pooled odds ratios (ORs) with 95% confidence intervals (CIs) for endometrial cancer risk, with the Chi-square-based Q-test used to test for heterogeneity. Begg's and Egger's tests were adopted to check publication bias. RESULTS: Six published case-control studies of association between the CYP1B1 C4326G polymorphism and endometrial cancer risk covering 6,577 subjects were included in the meta-analysis, but the results indicated no significant correlation with allele contrast and genotype comparisons (G vs C: OR 1.01, 95% CI 0.93-1.09; GG vs CC: OR 1.04, 95% CI 0.88-1.23; CG + GG vs CC: OR 1.08, 95% CI 0.97-1.21; GG vs CC + CG: OR 1.01, 95% CI 0.87-1.17). Heterogeneity hypothesis test did not reveal any heterogeneity and Begg's and Egger's tests did not detect obvious publication bias. CONCLUSIONS: There is no association between the CYP1B1 C4326G polymorphism and endometrial cancer risk. PMID- 22296382 TI - Transcriptome-wide network analysis of squamous lung cancer reveals potential methylation genes. AB - Lung cancer is a prevalent cancer with a high death rate. Underlying mechanisms have been found to be highly correlated with epigenetics, especially with DNA methylation. With methylation array and other regulation data, we constructed a TF-gene regulation network and a TF-pathway network. Through those networks, we identified lung cancer related genes that were found by previous studies, and supposed a number of new examples. Our work demonstrated the new potential methylation for lung cancer. PMID- 22296383 TI - Multivariate disease mapping of seven prevalent cancers in Iran using a shared component model. AB - BACKGROUND: The aim of this study was to model the geographical variation in incidence and risk factors of seven prevalent cancers in Iran. METHODS: The data for cancers of esophagus, stomach, bladder, colorectal, lung, prostate, and female breast along with their risk factors in all 30 provinces of Iran for the year 2007 were included into study. Smoking, overweight, inadequate consumption of fruits and vegetables, socioeconomic status and low physical activity were studied as risk factors. Standardized incidence ratios were estimated using full bayesian model. In addition, the shared component model was used to explore the spatial pattern of the cancers and to estimate the relative importance of their corresponding risk factors. RESULTS: Fars and the Northwestern provinces were observed as high risk areas and Hormozgan (a Persian Gulf coastal province), Sistan and Baluchestan, South Khorasan, and Kerman provinces located in Southeast were areas of low risk for most cancers. For all five risk factors, larger effects on incidence of the relevant cancers were found in the Northern provinces compared to other areas. Smoking, overweight, inadequate consumption of fruit and vegetable, socioeconomic status, and low physical activity were found to have more effects on incidence of stomach, breast, esophagus, and breast cancers, respectively. CONCLUSIONS: Most of the high risk areas for seven cancers were in accordance with the results for spatial patterns of related risk factors and their relative weights on relevant cancers. The multivariate shared component model of the seven cancers achieves a considerable improvement in terms of Deviance Information Criterion over the individual modeling of diseases. PMID- 22296384 TI - Survival analysis of patients with esophageal cancer using parametric cure model. AB - BACKGROUND AND OBJECTIVES: Esophageal cancer is a major cause of mortality and morbidity in the Caspian littoral north-eastern part of Iran. The aim of this study was to calculate cure function as well as to identify the factors that are related to this function among patients with esophageal cancer in this geographical area. METHODS: Three hundred fifty nine cases of esophageal cancer registered in the Babol cancer registry during the period of 1990 to 1991 (inclusive) were followed up for 15 years up to 2006. Parametric cure model was used to calculate cure fraction and investigate the factors responsible for probability of cure among patients. RESULTS: Sample of subjects encompassed 62.7% men and 37.3% women, with mean ages of diagnosis was 60.0 and 55.3 years, respectively. The median survival time reached about 9 months and estimated survival rates in 1, 3, and 5 years following diagnosis were 23%, 15% and 13%, respectively. Results show the family history affects the cured fraction independently of its effect on early outcome and has a significant effect on the probability of uncured. The average cure fraction was estimated to be 0.10. CONCLUSION: As the proportionality assumption of Cox model does not meet in certain circumstances, a parametric cure model can provide a better fit and a better description of survival related outcome. PMID- 22296385 TI - Setting research priorities to reduce burden of cancer in Iran: an institutional experience. AB - OBJECTIVE: The aim of this study was to draw a set of priority areas of cancer research in order to utilize these priorities as broader policy for decision making on a comprehensive cancer control program at the national level in Iran. MATERIALS AND METHODS: A steering committee consisting of scientists from the three major areas of clinical, basic research and public health sciences recommended a qualitative study of ranking an exhaustive outlines of cancer science topics by cancer scientists throughout country. Scientists were identified through Medline search and contacting cancer research centers all over the country. An exhausting outline of cancer science topics was modified and posed to Iranian cancer scientists. Doing research on each outlined topic was judged based on its state of being necessary, appropriate, practical or yielding in the Iranian societal context. An electronic system of communication was developed and all scientists were asked to rank each topic based in order of 1 to 5. As the areas of expertise of scientists were diverse, the participants had the option to rank the outlined topics that they think suitable to their areas. RESULTS: Out of 135 identified scientists, 108 participated of whom 56 were clinicians (M.D's with university appointment), 35 basic scientists and 17 epidemiologists and public health scientists. As the top first five areas of research priorities, the overall assessment indicated as research topics: 1) cancer surveillance and registration as the first priority; followed by 2) exogenous factors in the origin and cause of cancer; 3) surveillance--patient care and survivorship issues; 4) issues of end-of-life care; and 5) cost analyses and health care delivery of cancer services. CONCLUSION: The study concluded that research on infrastructure of cancer control programs, cancer registration, service delivery and patient quality of life bears higher priority in Iran. PMID- 22296386 TI - The risk of colorectal cancer is associated with the frequency of meat consumption in a population-based cohort in Korea. AB - OBJECTIVE: To date, there have been few prospective cohort studies that have investigated the association between meat consumption and the risk of colorectal cancer (CRC) in Asian countries. A large, population-based cohort study was conducted to assess the effect of the frequency of meat consumption on the risk of CRC in Korean adults. METHODS: The participants were Korean government employees, school faculty members, and their unemployed dependents, aged 30-80 years, who underwent health examinations between 1996 and 1997. In 2003, information on CRC incidence was obtained during the 6-7 year follow-up period. The final data analysis included 2,248,129 study subjects. The hazard ratio (HR) and 95% confidence interval (CI) of the HR were estimated using the Cox proportional hazards regression model. RESULTS: During the follow-up period, CRC occurred in 4,501 men and 1,943 women (64.19 and 36.34 for age-standardized incidence rates per 100,000 person-years, respectively). In the total population, the estimated HRs and 95% CI for meat consumption of 2-3 times per week and more than 4 times per week compared with consumption of less than once per week were 1.06 (1.01-1.12) and 1.23 (1.13-1.35), respectively. In men only and women only groups, the HRs (95% CI) for consumption of more than 4 times per week compared with consumption of less than once per week were 1.13 (1.02-1.26) and 1.42 (1.21 1.66), respectively. CONCLUSION: The present findings suggest that frequency of meat consumption is positively associated with the risk of CRC. PMID- 22296387 TI - Nutritional epidemiology of cancer in Korea: recent accomplishments and future directions. AB - Because diet is closely related to cancer incidence and mortality, recent studies in cancer epidemiology have focused on dietary factors. The results of studies on nutritional cancer epidemiology in Korea are discussed in this research paper. Most studies have used a case-control design focused on breast or gastric cancer patients. Antioxidants were associated with a reduced risk of gastric cancer in most studies, but this association was not observed for breast cancer. Most diets consumed by Koreans that included fruits and vegetables were associated with reduced cancer risk, but high concentrations of salt in food were positively associated with gastric cancer risk. Genetic susceptibility was considered in several studies, and food contaminants were assessed to estimate life-time cancer risk. Recent studies have made advances in understanding the relationship between diet and cancer among Korean populations. However, because the history of nutritional cancer epidemiology in Korea is relatively short, the subjects covered and methodology of the research have been limited. A cohort design with a large sample size and appropriate methods to assess subjects' usual intake may be needed to determine the true association between diet and cancer in the future. PMID- 22296388 TI - Cancer chemopreventive potential of the Egyptian flaxseed oil in a rat colon carcinogenesis bioassay--implications for its mechanism of action. AB - The possible chemopreventive effects of natural Egyptian flaxseed oil on preneoplasia and cancer formation were investigated in a rat medium-term colon carcinogenesis bioassay. Male Wistar rats were divided into 6 groups. Groups 1, 3 and 5 were initiated by 1,2-dimethylhydrazine (DMH) 20 mg/kg body weight s.c. 8 times, twice a week to initiate colon carcinogenesis. Groups 1 and 3 received 20% or 5% flaxseed oil respectively in diet in post initiation stage until the end. Groups 2 and 4 served as a flaxseed dose corresponding controls without carcinogen initiation, while rats in group 6 served as negative controls. Distribution and total numbers of aberrant crypt foci (ACF), putative preneoplastic lesions, particularly those with >=4 aberrant crypts (ACs), and the numbers and sizes of colon tumors (adenoma and carcinoma) were significantly decreased by both treatment doses of flaxseeds as compared to group 5. Histochemical investigation revealed that the numbers of mucus-secreting cells in the colonic mucosa were reduced gradually during progression of colon carcinogenesis. Intriguingly, flaxseed oil caused the numbers and integrity of the mucus-secreting cells to retain close to normal levels and in a dose dependent manner. Moreover, the hematological parameters were almost constant between the groups particularly at the dose of 5% as compared to groups 5 and 6. PCNA-labeled indexes (PCNA-LI) in the DMH-initiated colonic mucosa were found to be decreased by both doses of flaxseeds administration. In conclusion, the present study showed that the post initiation dietary administration of flaxseeds oil suppressed DMH-induced colon carcinogenesis in rats without significant side effects. The mechanism is likely to be through its inhibitory effects on early cellular proliferation and modulation of mucin secretion properties in the initiated colonic mucosa. PMID- 22296389 TI - Personal use of hair dyes--increased risk of non-Hodgkin's lymphoma in Thailand. AB - The use of hair dyes has been inconsistently associated with an increased risk of lymphomas. To further evaluate this possibility, we examined hair dye use and lymphoma risk in a case-control study in the Thai population. A total of 390 histologically confirmed incident non-Hodgkin's lymphoma (NHL) cases and 422 controls were included. Information on hair dye use was obtained through a personal interview together with information on other known risk factors of lymphoma. Analysis was performed using logistic regression; odds ratios (ORs) estimates and 95% confidence intervals (CI) were calculated. Ever use of hair dyes was not associated with an increase risk of NHL both overall (OR=1.1, 95%CI 0.8-1.5) and in women (OR=1.4, 95%CI 0.9-2.3). However, NHL was significantly higher among persons who began using hair dyes before 1980 (OR=2.1, 95%CI 1.0 4.1). An increased risk was also observed among women who reported use of permanent hair dye product (OR=1.8, 95% CI 1.0-3.1). Analyses by NHL subtype showed an increased risk for diffuse large B-cell lymphoma among users of permanent hair dyes (OR=1.6, 95%CI 1.0-2.5) while follicular lymphoma was associated with the use of dark-colored dyes (OR=3.7, 95%CI 1.1-12.8). No association was observed with duration of use, nor total lifetime applications. These results indicate that personal hair dye use may play role in risks of NHL among person who used hair dyes before 1980. PMID- 22296390 TI - Estimating prevalence of genital warts in Turkey: survey among KETEM-affiliated gynecologists across Turkey. AB - BACKGROUND AND PURPOSE: In order to develop cost effective health strategies regarding HPV screening and prevention methods, determining the incidence and prevalence of HPV as well as the diseases it gives rise to such as cervical cancer and genital warts is essential. This study is a first step in determining nationwide annual prevalence of genital warts in Turkey. PATIENTS AND METHODS: Through the survey sent to gynecologists in each city in Turkey, a record number of data for 4,013,084 patients, out of which 5511 diagnosed with genital warts were collected from 81 cities. The survey was sent in May 2011 and recollected in July 2011. The data belonged to patients consulted in 2010. Patients ranged between women 30-65 years old. The prevalence per city was projected using population per city as presented in Turkish Statistical Institute (TUIK). The treatment types prescribed and conducted for each patient and number of referrals were also collected. RESULTS: The annual prevalence of 154 per 100,000 women aged 30-65 was found as the Turkey average. Given 15-37% recurrence rate estimates based on distribution of treatments provided in Turkey, an annual incidence of 97 131 per 100,000 women is estimated. Wide regional differences were observed across regions, with Aegean Region having the highest and the Southern Eastern regions having the lowest annual prevalence rates in Turkey. CONCLUSION: The annual prevalence rates and extrapolated incidence rates are comparable to incidences in European countries where intensive research into treatment of HPV and national health strategies are developed. Turkey should deepen its research in this area. This study contributes to these efforts as a first step in determining cost effective national health strategies. PMID- 22296391 TI - Prevalence of obesity among women in Turkey: analysis of KETEM data. AB - BACKGROUND AND PURPOSE: Determining the prevalence of obesity is a crucial step in combating with obesity and devising national health strategies. It is particularly important to better understand prevalence of obesity among women as women in Turkey also highly impacts the dietary habits of the whole household. This article determines the prevalence of obesity among adult women in the country. PATIENTS AND METHODS: Each Cancer Early Diagnosis and Screening Center were asked to submit data on BMI indices for women who visited the centers between January and June 2011. The data were collected on January 1 and July 1 first for each respective quarter. Patients ranged between 30-65 years old. World Health Organization guidelines on BMI cutoffs were used to determine the prevalence of obesity and overweight. RESULTS: The prevalence of obesity of adult women aged 35-60 was found to be 35%. The highest prevalence was observed in Western part of Turkey in the Aegean region with 42% of women with BMI over 30. The lowest rate was observed in the Eastern Turkey with 21% obese women, followed by 28% in Southeastern Turkey. CONCLUSION: The prevalence of obesity among adult women in Turkey is very comparable to some of the other countries with highest rates of obesity in the world. Women specific health strategies against obesity should be devised. PMID- 22296392 TI - MDR1 gene C3435T polymorphism is associated with clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy. AB - OBJECTIVE: To evaluate the impact of the multi-drug resistance 1(MDR1) C3435T polymorphism on clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy. METHODS: From January 2005 to December 2008, 102 patients with surgically resected gastric cancers were enrolled into this study in the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University. The polymorphism was tested using real time polymerase chain reaction (RT-PCR) cycling probes and the relationship with clinical outcomes after postoperative adjuvant chemotherapy was analyzed by SPSS 17.0. RESULTS: The CT/TT genotype of C3435T was significantly associated with a shorter progression-free survival (PFS) and overall survival (OS) compared with the CC genotype [PFS: adjusted hazard ratio (HR) = 2.01, 95% confidence intervals (CI): 1.17-3.45, P = 0.012; OS: adjusted HR = 2.37, 95% CI: 1.31-4.28, P = 0.004]. TNM stage was also associated with PFS (adjusted HR = 2.33, 95% CI: 1.34-4.05, P = 0.003) and OS (adjusted HR = 2.62, 95% CI: 1.44-4.76, P = 0.002) in gastric cancer patients treated with postoperative adjuvant chemotherapy. CONCLUSION: Our results suggest that the MDR1 gene C3435T polymorphism is associated with clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy. This now needs to be confirmed by a randomized prospectively controlled study. PMID- 22296393 TI - Predictive role of molecular subtypes in response to neoadjuvant chemotherapy in breast cancer patients in Northeast China. AB - INTRODUCTION: Breast cancer is increasingly regarded as a heterogeneous disease which can be classified into distinct molecular subtypes with prognostic significance. MATERIALS AND METHODS: ER, PR, HER2 and ki-67 were used to divided 102 breast cancers treated with neoadjuvant chemotherapy (NCT) into 4 subtypes: luminal A (ER+, PR+, HER2-, and ki-67<=14%), luminal B (ER+, PR+, HER2- and ki 67>14% ; ER+ and/or PR+, HER2+), HER2-overexpression (ER-, PR- and HER2+) and triple-negative (ER-, PR-, and HER2-). RESULTS: Among 102 patients, a pCR was seen in 16 (15.7%) patients. The pathologic complete remission (pC) rates according to different subtypes are as follows: luminal A, 0 of 20 (0.0%), luminal B, 2 of 23 (8.7%), HER2-overexpression 4 of 18 (22.2%), and triple negative, 10 of 41 (24.4%) (p=0.041). In triple-negative subtype patients, the rates of pCR differed significantly among the 3 chemotherapy regimens with 5.6% (1/18) for CEF (cyclophosphamide, epirubicin and flurouracil), 20.0% (1/5) for TE (docetaxel and epirubicin) and 44.4% (8/18) for TCb (docetaxel and carboplatin) (p=0.024). In locally advanced breast cancer patients, the rates of pCR seem to differ among the 3 chemotherapy regimens with 6.7% (2/30) for CEF, 0.0% (0/8) for TE and 23.1% (6/26) for TCb, but this did not attain statistical significance (p>0.05). CONCLUSIONS: Molecular subtypes are good predictors for response to NCT in breast cancer patients in Northeast China. Compared with luminal A tumors, HER2-overexpression and triple-negative subtypes are more sensitive to NCT. For triple-negative breast cancer, we concluded that the TCb combination is a promising NCT regimen. Our results also indicated that the TCb combination is promising for the treatment of locally advanced breast cancer. PMID- 22296394 TI - Knowledge, attitude and preventive practices of women for breast cancer in the educational institutions of Lahore, Pakistan. AB - Breast cancer incidence rates, pattern of presentation and survival rates vary worldwide. High incidence, advanced stage disease presentation and low survival rates have been reported from Pakistan. Lack of awareness and screening facilities along with poor socioeconomic status are the main causes. A survey based upon multiple choice questionnaires was conducted during an awareness campaign in women educational institutions of Lahore, to assess the baseline knowledge, attitude towards breast self examination (BSE), clinical breast examination (CBE) and source of information used by them. 1155 filled questionnaires were analyzed by SPSS version 12. The majority (83.7%) of the respondents were <30 years old, 60% had >10 and 31.5% had <14 years of education. Only 27% had "good" while 14% had "poor" and 59% had "fair" knowledge scores about breast cancer. Television was the most commonly cited source of information but was associated with lower knowledge score. The knowledge scores and practice of BSE had a positive association with education level. The respondents had better knowledge of life time risk and association of early diagnosis with better chances of cure, but worse knowledge of risk factors as compared to women in educational institutions of other countries. Generally the respondents of present study had low level of knowledge of breast cancer. Properly designed awareness campaign on television and in educational institutions can be effective to raise the knowledge level, the best long term strategy for this purpose. PMID- 22296395 TI - Role of xenoestrogens and endogenous sources of estrogens on the occurrence of premenopausal breast cancer in Iran. AB - Breast cancer affects Iranian women one decade younger than their counterparts in other countries and the underlying risk factors have remained controversial. The aryl hydrocarbon receptor (AhR) mediates endocrine disruptive activities of polyaromatic hydrocarbons (PAHs) and dioxins, which may compromise ovarian functions of women in polluted environments. This study focused on tissue expression levels of AhR and associations with exposure to chemicals with estrogen-like activities (xenoestrogens) and other reproductive factors in premenopausal breast cancer patients. Fifty cases who underwent surgery from June 2009 to June 2010 were matched with 100 controls by age and hospital records. AhR overexpression was detected in 87% of epithelial cells of young breast cancer patients. Living near factories generating PAHs and dioxins was considered as a major risk factor in premenopausal breast cancer (p=0.001, OR=4.8). History of idiopathic infertility was identified as a second significant risk factor (p=0.002, OR=3.50), which could be affected by endogenous estrogen levels. Long term (>5 yrs) consumption of oral contraceptive pills was identified as the third most important risk factor (p=0.006, OR=2.27). Adiposity and abnormal weight gain after 18 years were considered as two major background factors, which may contribute to the levels of endogenous estrogens. Direct and indirect exposure to cigarette smoke (p=0.005, OR=1.43) was considered as a weak risk factor without association with AhR levels. It seems that AhR overexpression is affected by exposure to xenoestrogens and by adiposity. Early occurrence of breast cancer in Iran may be a result of interactions between hormonal and environmental factors. PMID- 22296396 TI - Association between glycodelin and aryl hydrocarbon receptor in Iranian breast cancer patients: impact of environmental endocrine disrupting chemicals. AB - Breast cancer affects Iranian women one decade younger than their counterparts in other countries and the underlying risk factors have remained controversial. The aryl hydrocarbon receptor (AhR) mediates the effects of many environmental endocrine disruptors and contributes to the many other genes and Gd is an endocrine-regulated glycoprotein which may induce by AhR ligands in endometrium. This study has aimed to compare the interactions between Gd and AhR and other fundamental genes (p53, K-Ras, ER, PgR, AR) between pre and post menopausal Iranian breast cancer patients. To conduct immunohistochemical studies with appropriate monoclonal antibodies, 25 premenopausal invasive ductal carcinomas and 29 postmenopausal invasive ductal carcinomas were selected retrospectively in 2008-2010 from the pathology department of Imam Khomeini hospital complex of Tehran. Higher levels of AhR in epithelial cells of premenopausal patients and breast fibroadenoma emphasized the susceptibility of these cells to environmental induced tumors. Current study demonstrated a significant association between tumoral levels of Gd and AhR (p=0.002) in breast cancers which confirms the preliminary hypothesis about the role of TCDD exposure on Gd biosynthesis and secretion in TCDD-treated endometrial epithelial cells. In summary this study showed the dual prognostic role of Gd especially in premenopausal breast cancer which could be induced by AhR overexpression. Further studies are necessary to find the direct role of breast carcinogens as well as endocrine disrupting chemicals on the differential levels of Gd in breast tumors. PMID- 22296397 TI - Healthcare utilization in patients with esophageal cancer in a high risk area in northeast of Iran. AB - INTRODUCTION: Golestan, a province located north of Persian Gulf in northeastern part of Iran is a well known area for high risk of esophageal cancer (EC) in the world. There is no information about healthcare utilization in populations residing in the area. This study was conducted to assess utilization of healthcare and its associated factors among esophageal cancer patients in this region as well as to address ethical implication of this utilization. METHODS: All new cases of EC in Golestan province during year of 2007 were recruited. Seven diagnostic and five therapeutic services were used to assess diagnostic utilization index (DUI), and therapeutic utilization index (TUI), respectively. Multivariate regression analysis was used to assess the relationship between variables and DUI or TUI. P-value of less than 0.05 was considered as statistically significant. RESULTS: Tow hundred twenty three, patients were enrolled with mean (Standard Deviation) age of 64.3 (12.5) years with 57.8% male. We observed that occupation (P<0.01), ethnicity (P<0.01) and sex (P=0.03) were strongly associated with DUI. Insurance coverage (P<0.01), place of residency (P<0.01), and occupation (P=0.01) were associated with TUI. CONCLUSION: We concluded that several factors contribute to disparity in healthcare utilization in the studied population. PMID- 22296398 TI - Assessment of risk factors affecting recurrence of patients with gastric cancer in the presence of informative censoring in Iran. AB - BACKGROUND: In some survival studies, several events are taken into consideration. If the events are independent then the ordinary methods such as Kaplan-Meier, Cox or parametric models can be used. If one of the events dependently (informatively) censors the other, the results are biased. The present study was designed to assess the risk factors for recurrence of patients with gastric cancer in the presence of informative censoring using parametric models with a semi-competing risk approach. MATERIALS AND METHODS: In a retrospective study, 408 cases of gastric cancer were selected from the patients referred to the Tehran Cancer Institute from March 2003 to March 2007. Gender, age at diagnosis, distant metastasis, tumor size, histology type, tumor grade, pathologic stage, tumor site, and type of treatment were studied as prognostic factors and used in the models. Parametric models such as Weibull, exponential, log-logistic were used with informative right censoring using Akaike Information Criteria (AIC) as criteria to compare models. The data were analyzed using R statistical software. A p-value of less than 0.05 was considered as statistically significant. RESULTS: Based on Akaike information criteria (AIC), the Weibull model best fitted to data. The effect of tumor size and pathologic stage were significant on recurrence in both univariate and multivariate analyses. Tumor site and tumor grade were significant only in univariate analysis. CONCLUSIONS: The results showed that semi-competing risk methods perform well in determining risk factors for disease recurrence. PMID- 22296399 TI - Low frequency of human T-cell lymphotropic virus 1 antibodies in Iranian gastric cancer patients in comparison to controls. AB - There is some evidence that human T-cell lymphotropic virus (HTLV-1) infection has a reverse association with gastric cancer (GC). Data about this association in the Iranian population are scarce. In this study we therefore assessed the frequency of anti-HTLV-1 antibody in GC patients and compare it to antibody presence in healthy individuals in Iranian population. This case control study was performed between 2008-2011 on 201 GC patients and 219 control subjects. HTLV 1 antibodies were assessed by ELISA and the positive results were confirmed by western blotting. Totals of 201 gastric cancer patients and 219 controls were enrolled in this study. The tumors in the majority of patients (45.3%) were in the distal (non-cardia) area. Mean age of patients at the time of diagnosis was 59.2+/-12.5 and mean age of controls was 57.7+/-11.3. While only one GC patient (0.5%) was positive for HTLV-1 antibody, there were four individuals (1.89%) from the control group with antibodies. In addition, smoking had statistically significant relationship with cancer (P=0.001). Our study showed that the frequency of HTLV-1 antibody in patients was lower than in controls, similar to the results obtained in Japan. Further investigations with a larger sample size are needed in order to determine the association between GC and HTLV-1 infection in Iran. PMID- 22296400 TI - Accuracy of colposcopically directed biopsy in diagnosis of cervical pathology at Srinagarind Hospital. AB - OBJECTIVE: To determine the accuracy of colposcopically directed biopsy (CDB) in diagnosis of precancerous or cancerous lesion of the uterine cervix as a quality index of the institute. MATERIALS AND METHODS: We retrospectively reviewed the medical records of the women who had colposcopic examination at the Department of Obstetrics and Gynecology, Srinagarind Hospital from January, 2005 to December, 2010. The women with satisfactory colposcopic examination who had CDB and further interventions such as loop electrosurgical excision procedure (LEEP)/conization, and/or hysterectomy were included in study. The pathological reports of the specimens from CDB were analyzed comparing with LEEP/conization or hysterectomy according to the highest degree of abnormalities. Pathological reports of HSIL (high grade squamous intraepithelial lesion) or more severe were classified as positive, while LSIL (low grade squamous intraepithelial lesion) or less severe were classified as negative. RESULTS: There were 320 patients included, 259 having highest pathological reports of HSIL or more. The accuracy of CDB to detect HSIL or more of the uterine cervix was 87.8% with sensitivity, specificity, PPV and NPV of 84.9%, 100%, 100%, and 61%, respectively. CONCLUSIONS: The accuracy of CDB in diagnosis of cervical pathology in our institute was acceptable and comparable to those of others. CDB is a reliable method to obtain the pathological diagnosis in women with abnormal cervical cytologic screening. PMID- 22296401 TI - No association of the exonuclease 1 T439M polymorphism and risk of hepatocellular carcinoma development in the Turkish population: a case-control study. AB - Exonuclease 1 (Exo 1) is an important nuclease involved in the mismatch repair system that contributes to maintaining genomic stability, modulating DNA recombination and mediating cell cycle arrest. A cytosine (C)/thymine (T) common single nucleotide polymorphism (SNP) at second position of codon 439 in exon 10 of Exo 1 determines a threonine (Thr, T) to methionine (Met, M) (T439M) aminoacidic substitution which may alter cancer risk by influencing the activity of Exo 1 protein. The association of Exo 1 T439M polymorphism with hepatocellular carcinoma (HCC) susceptibility has yet to be investigated. To assess this possibility in a Turkish population, a hospital-based case-control study was designed consisting of 224 subjects with HCC and 224 cancer-free control subjects matched for age, gender, smoking and alcohol status. The genotype frequency of the Exo 1 T439M polymorphism was determined by using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. No statistically significant differences were found in the allele or genotype distributions of the Exo 1 T439M polymorphism among HCC and cancer-free control subjects (P>0.05). Our result demonstrates for the first time that the Exo 1 T439M polymorphism does not have a major role in genetic susceptibility to hepatocarcinogenesis, at least in the population studied here. Independent studies are need to validate our findings in a larger series, as well as in patients of different ethnic origins. PMID- 22296402 TI - Service quality perceptions in primary health care centres in Greece. AB - CONTEXT: The paper refers to the increased competition between health care providers and the need for patient-centred services in Greece. Using service quality methodology, this paper investigates service quality perceptions of patients in Greek public primary health centres. OBJECTIVE: To test the internal consistency and applicability of SERVQUAL in primary health care centres in Greece. STRATEGY: SERVQUAL was used to examine whether patients have different expectations from health care providers and whether different groups of patients may consider some dimensions of care more important than others. RESULTS: The analysis showed that there were gaps in all dimensions measured by SERVQUAL. The largest gap was detected in empathy. Further analysis showed that there were also differences depending on gender, age and education levels. A separate analysis of expectations and perceptions revealed that this gap was because of differences in patients' perceptions rather than expectations. DISCUSSION AND CONCLUSIONS: THIS paper raises a number of issues that concern the applicability of SERVQUAL in health care services and could enhance current discussions about SERVQUAL improvement. Quality of health care needs to be redefined by encompassing multiple dimensions. Beyond a simple expectations-perceptions gap, people may hold different understandings of health care that, in turn, influence their perception of the quality of services. PMID- 22296403 TI - Common variants of transcription factor 7-like 2 (TCF7L2) are associated with reduced insulin secretion in women with polycystic ovary syndrome. AB - Common variants of the transcription factor 7-like 2 (TCF7L2) gene were identified as one of the few genetic polymorphisms with powerful effects on the risk of type 2 diabetes (T2D). Given the genetic overlap between polycystic ovary syndrome (PCOS) and T2D, the present study was undertaken to investigate whether the TCF7L2 variants are also associated with PCOS. We analyzed single nucleotide polymorphisms (SNPs) rs11196218 and rs290487 of the TCF7L2 gene, which showed robust associations with T2D in Chinese population, in 430 PCOS patients and 360 control subjects by pyrosequencing, and also assessed the effect of genotype on clinical and biochemical traits in the PCOS group. We found no evidence for association between SNP rs11196218 and PCOS. The SNP rs290487 showed marginal differences in genotype frequencies between the PCOS and control group, with the minor C allele being the at-risk allele for PCOS. In PCOS women, the C allele carriers of rs290487 had higher levels of 2h blood glucose but lower insulinogenic index than noncarriers, suggesting impaired insulin secretion. Our data suggested that the TCF7L2 variants may confer an increased risk for early impairment of glucose homeostasis in PCOS. PMID- 22296404 TI - Evaluation of a wireless ambulatory capsule (SmartPill(r)) to measure gastrointestinal tract pH, luminal pressure and temperature, and transit time in ponies. AB - REASONS FOR PERFORMING STUDY: This study investigated the use of a wireless ambulatory capsule (WAC; SmartPill((r)) pH.p GI Monitoring System) to determine WAC-gastric emptying time (GET) in ponies. OBJECTIVES: To measure WAC-GET and compare it to those findings with GET assessed by nuclear scintigraphy (S-GET). HYPOTHESIS: WAC-GET will be slower than S-GET, but will be significantly correlated. METHODS: Seven healthy adult mixed-breed pony mares were used in this study. Feed was withheld for 12 h prior to the WAC administration. After administration, a complete-feed diet was fed to allow the WAC to pass into the stomach. Luminal pH, temperature and pressure were collected by a modified receiver secured to the pony. Once the pH reached a value of >= 8.0, it was determined that gastric emptying had occurred, and ponies were fed grass hay. After 5 days, data were downloaded and analysed using proprietary software. During the second period of the study, after at least 2 weeks, 4 of the ponies underwent a standard S-GET test. RESULTS: The WAC was successfully administered, and data were collected from all ponies. The mean percentage of data packets collected by the receiver was 84.9 +/- 3.51% (range 66.8-95.1%). Mean WAC-GET was 7.38 h (range 0.15-46.65 h). Mean gastric pH was 4.75 (range 2.07-6.99). Mean small intestinal transit time was 4.6 h. The mean pH for the small intestine was 8.0. The mean S-GET time (in hours) when 10% of the radioactive feed is present in the stomach (T-90%) was 2.3 h. The S-GET did not correlate significantly with the WAC-GET. CONCLUSIONS AND POTENTIAL RELEVANCE: The WAC was safely administered to ponies, and data were collected using a modified receiver. The WAC-GET varied considerably between ponies, but was <= 3 h in 5 of the 6 ponies. The WAC used in this study provided a noninvasive technique that produced novel information about the pony gastrointestinal tract, but owing to the substantial variability in GET values and long transit time it may not be a reliable clinical tool at this time. PMID- 22296405 TI - Programmable self-assembly of antibody-oligonucleotide conjugates as small molecule and protein carriers. AB - Dihydrofolate reductase single-chain variable fragment (scFv) fusion proteins can be used for the targeted cellular delivery of oligonucleotides, conjugated small molecules, and proteins via labeling of oligonucleotides by bis-methotrexate. PMID- 22296406 TI - Radiation-induced fragmentation of diamide extraction agents in ionic liquid diluents. AB - N,N,N',N'-Tetraalkyldiglycolamides are extracting agents that are used for liquid liquid extraction of trivalent metal ions in wet processing of spent nuclear fuel. This application places such agents in contact with the decaying radionuclides, causing radiolysis of the agent in the organic diluent. Recent research seeks to replace common molecular diluents (such as n-dodecane) with hydrophobic room-temperature ionic liquids (ILs), which have superior solvation properties. In alkane diluents, rapid radiolytic deterioration of diglycolamide agents can be inhibited by addition of an aromatic cosolvent that scavenges highly reactive alkane radical cations before these oxidize the extracting agent. Do aromatic ILs exhibit a similar radioprotective effect? To answer this question, we used electron paramagnetic resonance spectroscopy to study the fragmentation pathways in radiolysis of neat diglycolamides, their model compounds, and their solutions in the ILs. Our study indicates that aromatic ILs do not protect these types of solutes from extensive radiolytic damage. Previous research indicated a similar lack of protection for crown ethers, whereas the ILs readily protected di- and trialkyl phosphates (another large class of metal extracting agents). Our analysis of these unanticipated failures suggests that new types of organic anions are required in order to formulate ILs capable of radioprotection for these classes of solutes. This study is a cautionary tale of the fallacy of analogical thinking when applied to an entirely new and insufficiently understood class of chemical materials. PMID- 22296407 TI - Apocynin reduces reactive oxygen species concentrations in exhaled breath condensate in asthmatics. AB - Asthma is an inflammatory airway disease, and oxidative stress was proven to be involved in its pathogenesis. Apocynin effectively inhibits the main source of reactive oxygen species (ROS)-nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-by blocking its activation. The aim of this study was to investigate the effect of inhaled apocynin on ROS and RNS (reactive nitrogen species) concentration in 14 nonsmoking mild asthmatics. Effects of nebulized apocynin (0.5 mg/mL) were assessed in exhaled breath condensate (EBC) after 30, 60, and 120 minutes, and safety parameters have been analyzed. Apocynin significantly decreased H2O2 concentration in EBC in comparison with placebo after 60 and 120 minutes. Moreover, apocynin significantly reduced NO(-2) concentration 30 and 60 minutes after nebulization and caused a significant decrease of NO(-3) concentration in EBC 60 and 120 minutes after administration, comparing with placebo. No adverse events have been observed throughout the study. This research confirmed anti-inflammatory properties of nebulized apocynin, which might be an effective and safe drug in bronchial asthma. PMID- 22296408 TI - Streptococcus pneumoniae induces human beta-defensin-2 and -3 in human lung epithelium. AB - Streptococcus pneumoniae is an important causative agent of pneumonia in humans. Pulmonary epithelial surfaces constitutes not only a mechanical barrier against invading pathogens but also essentially contribute to innate immunity by producing antimicrobial peptides such as human beta-defensin-2 (hBD-2) and -3 (hBD-3). In this study the authors demonstrated that pneumococci induced hBD-2 and hBD-3 expression in human pulmonary epithelial cells. Further analysis indicated an essential role of Toll-like receptor 2 (TLR2) for the expression of both peptides in infected pulmonary epithelial cells. Whereas the hBD-2 release was controlled by the phosphoinositide 3-kinase (PI3K) and the transcription factor nuclear factor kappa B (NF-kappaB), hBD-3 was triggered via the c-Jun N terminal kinase (JNK)-activator protein 1 (AP-1) pathway. Additionally, the authors showed that exogenous hBD-2 as well as hBD-3 elicited a strong antimicrobial effect on S. pneumoniae. Thus, differential regulation of the expression of hBD-2 and hBD-3 might play an important role in pneumococci pneumonia. PMID- 22296409 TI - Silver as an example of the applications of photochemistry to the synthesis and uses of nanomaterials. AB - Photochemistry is a powerful tool for controlled synthesis of metal nanoparticles, their modification and in many of the applications that these materials have. Plasmon transitions offer a unique way of delivering energy with exquisite spatial and temporal control and can be used to advantage where visible wavelength control is required. This account of research at the University of Ottawa summarizes details of the synthesis, modification and applications of silver nanostructures. PMID- 22296410 TI - One- and three-dimensional growth of hydroxyapatite nanowires during sol-gel hydrothermal synthesis. AB - Nanoscale hydroxyapatite (HA) is an optimal candidate biomaterial for bone tissue engineering because of its bioactive and osteoconductive properties. In this study, micro- and nanoscale HA particles with rod- and wirelike morphology were synthesized by a novel sol-gel-hydrothermal process. Sol-gel chemistry was used to produce a dry gel containing amorphous calcium phosphate (ACP), which was used as a precursor material in a hydrothermal process. The sol-gel-hydrothermal products were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) to determine particle morphology, crystal structure, and the presence of chemical functional groups. A pure HA crystal was synthesized, which underwent both one- and three-dimensional growth, resulting in tunable microrod and nanorod, and wire morphologies. The effects of solution pH and reaction time on particle diameter and length were assessed. Particle diameter ranged from 25 to 800 nm and decreased with an increase in solution pH, whereas both particle length and diameter increased as the hydrothermal process was prolonged. Nanowire HA powders (10-50 wt %) were mixed with poly(epsilon-caprolactone) (PCL) to produce PCL/HA composites. Fracture surfaces of PCL/HA composites showed a well-dispersed and homogeneous distribution of HA nanowires within the PCL matrix. Mechanical testing revealed a significant (p < 0.05) increase in the Young's and compressive moduli of PCL/HA composites compared to PCL alone, with 50 wt % HA producing a 3 fold increase in Young's modulus from 193 to 665 MPa and 2-fold increase in compressive modulus from 230 to 487 MPa. These HA nanowires can be used to reinforce polymer composites and are excellent biomaterials for tissue engineering of bone. PMID- 22296411 TI - In vitro exposure of Acer negundo pollen to atmospheric levels of SO2 and NO2: effects on allergenicity and germination. AB - In the last years, a rising trend of pollen allergies in urban areas has been attributed to atmospheric pollution. In this work, we investigated the effects of SO(2) and NO(2) on the protein content, allergenicity, and germination rate of Acer negundo pollen. A novel environmental chamber was assembled to exposure pollen samples with SO(2) or NO(2) at two different levels: just below and two times the atmospheric hour-limit value acceptable for human health protection in Europe. Results showed that protein content was lower in SO(2)-exposed pollen samples and slightly higher in NO(2)-exposed pollen compared to the control sample. No different polypeptide profiles were revealed by SDS-PAGE between exposed and nonexposed pollen, but the immunodetection assays indicated higher IgE recognition by all sera of sensitized patients to Acer negundo pollen extracts in all exposed samples in comparison to the nonexposed samples. A decrease in the germination rate of exposed in contrast to nonexposed pollen was verified, which was more pronounced for NO(2)-exposed samples. Our results indicated that in urban areas, concentrations of SO(2) and NO(2) below the limits established for human protection can indirectly aggravate pollen allergy on predisposed individuals and affect plant reproduction. PMID- 22296412 TI - Physical activity, social network type, and depressive symptoms in late life: an analysis of data from the National Social Life, Health and Aging Project. AB - OBJECTIVES: To clarify whether physical activity among older Americans is associated with depressive symptoms, beyond the effects of social network type, physical health, and sociodemographic characteristics. METHOD: The analysis used data from a sub-sample, aged 65-85, from the National Social Life, Health and Aging Project (N=1349). Hierarchical regressions examined the respective effects of selected network types and extent of engagement in physical activity on depressive symptoms, controlling for physical health and sociodemographic background. RESULTS: The findings showed that physical activity was correlated inversely with late life depressive symptoms. However, when interaction terms for the selected social network types and the extent of physical activity were also considered, the main effect of social network on depressive symptoms increased, while that of physical activity was eliminated. CONCLUSIONS: The results show that older American adults embedded in family network types are at risk of limited physical activity. However, interventions aimed to increase their engagement in physical activity might help to reduce depressive symptoms within this group. PMID- 22296413 TI - Palivizumab: a debate about funding. AB - A clinician and the chair of the hospital drug committee debate the merits of the use of palivizumab as prophylaxis against respiratory syncytial virus infection for a preterm baby with oxygen-dependent, chronic lung disease and discuss the issue of public funding of palivizumab. An ethicist comments on ethical aspects of the debate about cost-effectiveness. PMID- 22296414 TI - Fabrication of microgel-in-liposome particles with improved water retention. AB - Corneocytes represents the main water reservoir of stratum corneum, and that ability intimately arises from their architecture and total composition. Here we describe a novel method for fabricating a microgel-in-liposome (M-i-L) structure consisting of a sodium hyaluronate microgel and a lipid membrane envelop in order to mimic corneocyte cell structures. The essence of our approach is to use a lecithin-based microemulsion with a very low interfacial tension between the water droplet and oil continuous phase. Using this emulsion enables us to stabilize a dispersion of microgel particles without phase separation or aggregation. The addition of excess water produced single-core or multicore microgel particles enveloped in a lipid layer. To demonstrate the applicability of this unique vesicle system, we encapsulated a high concentration of natural moisturizing factor (NMF) in the microgel core and investigated how the M-i-L structure affected the water retention in comparison with other control systems. We have observed that our M-i-L particles with the NMF in the core, which mimicked the corneocyte cell structure, showed an excellent ability to retain water in the system. This experimental result inspired us to investigate how corneocyte cells, which feature a lipid-enveloped hydrogel structure, provide such long-lasting hydration to the skin. PMID- 22296415 TI - Urogynaecological problems in pregnancy. AB - The majority of urogynaecological problems can manifest during pregnancy or as a direct result of pregnancy and delivery. Those most commonly occurring during pregnancy are urinary tract infection, filling and voiding disorders, urinary incontinence, pelvic organ prolapse and faecal incontinence. The development of these may be as a result of physiological changes that occur in pregnancy or as a result of previous pregnancies. There may also be urogynaecological sequelae that occur as a result of trauma sustained during delivery. These include perineal and anal sphincter trauma, bladder or ureteric injuries during caesarean section or operative deliveries, and the development of vesico-vaginal or recto-vaginal fistulae. PMID- 22296416 TI - Adenomyosis and female fertility: a critical review of the evidence. AB - Adenomyosis is frequent during the evaluation of infertile women. Present evidence suggests that adenomyosis has a negative impact on female fertility. Limited data from uncontrolled studies suggest that treatment of adenomyosis may improve fertility. This review critically appraises the existing evidence to determine the relationship between adenomyosis and female fertility. There is need for large epidemiological studies to substantiate the association between adenomyosis and infertility. Furthermore, if adenomyosis has a harmful impact on fertility there is a need to determine if its treatment improves fertility and the various treatment modalities reported need to be assessed for their effectiveness in randomised trials. PMID- 22296417 TI - Pregnancy outcome following mid-trimester amniocentesis. AB - To determine the institutional pregnancy complications rate associated with genetic amniocentesis and ascertain whether procedural variables or pre-existing factors may determine an increased risk of having a procedural-related fetal loss, we retrospectively evaluated all the consecutive amniocentesis, with known pregnancy outcome (n = 2990), performed between January 2001 and December 2009 by two very experienced clinicians. The patients who had counselling in the same period but declined to undergo amniocentesis represent the control group (n = 487). A total of 30 fetal losses occurred within 24 weeks' gestation (1%), while in the control group, we had four losses (0.8%). Procedural variables (transplacental sample, multiple needle insertions and gestational age) were not found to be predictive of increased fetal loss rate. Previous vaginal bleeding increased the risk of pregnancy loss after amniocentesis with an OR 4.1 (95% CI 2.0-8.7); on the contrary, a history of two or more miscarriages is not associated with a greater fetal loss rate, while the increased percentage (OR 3.4, 95% CI 1.2-9.0) in patients affected by uterine myoma appears connected, after the comparison with the control group, with the presence of fibroids rather than procedure. PMID- 22296418 TI - Cyclooxygenase immunohistochemical staining in the human ductus arteriosus after 24 weeks of gestational age. AB - Cyclooxygenase inhibitors (CI) which contained risks to fetal health were one of the most effective tocolytics. In order to indirectly investigate the effects of CI in human ductus arteriosus, immunohistochemical staining for cyclooxygenase-1 (COX1) and cyclooxygenase-2 (COX2) was evaluated in post-mortem fetuses with gestational ages between 24 and 34 weeks. Neither COX1 nor COX2 staining was related to gestational age. COX1 and COX2 staining in the vessel walls were not related to each other. COX1 staining in the endothelium, inner media and outer media were positively correlated with each other (COX1 endothelium vs IM staining Spearman's rho statistic [rs] = 0.721, p = 0.001; COX1 endothelium vs OM staining [rs] = 0.634, p = 0.004; COX1 IM vs OM staining [rs] = 0.931, p = 0.001). COX2 staining of endothelium was not correlated with either IM or OM staining. In conclusion, COX2 staining in the post-mortem specimens of human ductus arteriosus between 24 and 34 weeks is weak and limited to the endothelium. PMID- 22296419 TI - Oxidative stress in pathological pregnancies. AB - Oxidative stress (OS) plays a role in pregnancy at risk of pre-eclampsia, diabetes and premature labour. We measured three markers of OS: total antioxidant capacity (TAC), thiolyte capacity and pro-oxidant capacity in 45 women: 15 normal pregnancies, 17 pathological pregnancies (pre-eclampsia and pregestational diabetes) and 13 delivered pre-term. Plasma TAC (MUmol/ml) values in patients with pathological pregnancies (235.67 +/- 70.08) (p(1) = 0.0086) and pre-term labour (243.51 +/- 50.52) (p(2) = 0.0479) were significantly reduced as compared with the controls (306.78 +/- 70.08). Thiolyte capacity (MUmol/ml) in the pathological pregnancies (326.03 +/- 78.24) (p(3) = 0.0029) and in pre-term labour (335.94 +/- 76.63) (p(4) = 0.0084) groups were significantly reduced compared with the control group (417.48 +/- 39.76) (p < 0.05). Pro-oxidant capacity (mg/100 ml) in the pathological pregnancies (94.11 +/- 26.13) (p(5) = 0.00034) and in pre-term labour (87.18 +/- 20.28) (p(6) = 0.00044) groups were significantly higher compared with the controls (60.27 +/- 6.33). Elevated OS values were seen in pathological pregnancies. This supports the important role of OS in diseases in pregnancy, particularly pre-eclampsia, diabetes and pre-term birth. PMID- 22296420 TI - Antenatal screening for pre-eclampsia: evaluation of the NICE and pre-eclampsia community guidelines. AB - The NICE and PRECOG guidelines are based on systematic reviews of risk factors for pre-eclampsia to identify mothers at risk before 20 weeks' gestation. Cases (64) and controls (112) were classified retrospectively as screen positive or negative as recommended by the two guidelines The NICE guideline had a higher sensitivity rate of 77% (95% CI 65-87%) vs 59% (95% CI 46-71%) but a lower specificity of 54% (95% CI 44-64%) vs 81% (95% CI 73-88%) with the PRECOG guideline. Based on an incidence of pre-eclampsia of 4% the positive predictive values of PRECOG and NICE guidelines were estimated at only 11% and 7%, respectively. The most discriminatory risk factor was history of pre-eclampsia in a previous pregnancy. Neither guideline has a reasonable performance and cannot be recommended for use in clinical practice. Resources should rather be focussed on development of new strategies to identify women at risk of pre-eclampsia. PMID- 22296421 TI - The Actim Partus test to predict pre-term birth in asymptomatic high-risk women. AB - The Actim Partus test has been shown to be a useful predictor of pre-term birth in symptomatic women, but limited research has been carried out in high-risk asymptomatic women. This is a pilot study to evaluate the use of this test as a direct comparator with the fetal fibronectin test. All asymptomatic high-risk women attending a pre-term surveillance clinic over a 9-month period, took an Actim Partus and fetal fibronectin test, between 23(+0)-24(+6) weeks' gestation. A total of 45 women were eligible. The positive and negative predictive values of the Actim Partus test for delivery at <= 37 weeks' gestation were 0% and 70%, respectively, compared with the fetal fibronectin test, with values of 67% and 79%, respectively. It was concluded that the Actim Partus test did not perform well as a predictor of pre-term birth in high-risk asymptomatic women. PMID- 22296422 TI - Treatment with magnesium sulphate in pre-term birth: a systematic review and meta analysis of observational studies. AB - Premature birth increases a child's risk of cerebral palsy and death. The aim of this work is to investigate the association between treatment with magnesium sulphate during premature deliveries and infants' cerebral palsy and mortality through a meta-analysis of observational studies. A comprehensive search of the Cochrane Library, EMBASE and the PubMed database from their inceptions to 1 October, 2010 using the keywords 'magnesium sulphate, children/infant/pre term/premature and cerebral palsy/mortality/morbidity/adverse effects/outcome' identified 11 reports of observational studies. Two authors working independently extracted the data. A meta-analysis of the data found an association between magnesium sulphate treatment and a significantly reduced risk of mortality (RR 0.73; 95% CI 0.61-0.89) and cerebral palsy (OR 0.64; 95% CI 0.47-0.89). Antenatal treatment with magnesium sulphate during premature deliveries seems to be associated with health benefits for the infants. The effective dose and timing, however, is not defined and given the lack of mechanistic understanding of the effect of MgSO(4), a reasonable alternative is a large-scale pragmatic clinical trial. PMID- 22296423 TI - Is it worth inducing labour in women with a previous caesarean delivery? AB - The aim of this study was to determine the outcome of labour induction following a previous caesarean section. A total of 43 cases were identified; 23 out of those (53.5%) achieved vaginal delivery. The remaining 20 cases (46.5%) had a repeat caesarean. A total of 25 women had >= 1 previous vaginal deliveries and in the remaining 18, the previous caesarean was the only pregnancy carried before the current pregnancy. Out of the 23 women who successfully delivered vaginally, 16 cases (69.6%) had a history of >= 1 previous vaginal delivery, while no such history was reported in the remaining seven cases (30.4%). The indications for a repeat caesarean were failed induction of labour in five cases (25%); fetal distress in seven cases (35%); failure-to-progress in eight cases (40%). Only one case (2.3%) of uterine rupture was reported. In conclusion, labour induction following a previous caesarean section is an effective and safe intervention. Vaginal delivery can be anticipated in the majority of these women. This study emphasises the need for thorough counselling of these women regarding benefits and risks of induction of labour, and also highlights the necessity of shared patient-doctor decision-making. PMID- 22296424 TI - A new objective scoring system for the prediction of successful induction of labour. AB - A prospective study was done in 311 women undergoing induction of labour for the formulation of a new score, which will be more objective than the conventional Bishop's score. Pre-induction cervical assessment was done by the transvaginal sonographic parameters followed by the digital examination. Labour induction was successful in 79.09%. A new score was formulated using the parameters having independent association and weighting of individual components was given according to its regression coefficients. A new score with a maximum value of 13 was proposed. The best cut-off point for the new score in receiver operating characteristics curve was six with a sensitivity of 95.5% and specificity of 84.6%. The new score was found to have a better area under the curve than the conventional score. PMID- 22296425 TI - High incidence of obstetric complications in Kassala Hospital, Eastern Sudan. AB - Medical files of women delivered at Kassala Hospital, Eastern Sudan in the period of January-December 2009 were reviewed retrospectively. Out of 4,689 delivered women, 14.7% were teenagers, 67.1% had no antenatal care and 12.6% were grandmultiparous. Obstetric complications included: pre-term birth (2.6%); pre eclampsia/eclampsia (4.2%); haemorrhage (2.9%); malpresentation (5.5%); obstructed labour (1.9%) and ruptured uterus (0.6%). Caesarean delivery rate was 31.1%. While 89.4% of the newborn babies were taken home, 6% were admitted to the nursery, 4.4% were stillbirths, and 0.2% immediate neonatal deaths. There were 26 maternal deaths (550 per 100,000 live births), mainly due to septicaemia (38.4%), haemorrhage (19.2%), embolism (15.3%) and malaria (11.5%). Thus, there is a high frequency of maternal morbidities and mortality which needs improvement in obstetric care. It is important to make visits from a tertiary hospital to the region to collect statistics and discuss management of the problems they reveal, with the local staff. PMID- 22296426 TI - Characteristics of pica practice during pregnancy in a sample of Argentine women. AB - The purpose of this study was to describe the practice of pica during pregnancy in Argentine women. Maternal and fetal characteristics as well as the practice of pica were evaluated during the puerperium in a sample of 1,014 women from five different geographical areas. Pica prevalence for the total sample was 23.2% (95% CI 20.6-25.8). Pagophagia (ice consumption) was the main type of pica practice, followed by geophagia (earth intake) and the ingestion of soap, toothpaste and chalk. The onset of the practice was mainly in the first months of pregnancy. A total of 49.8% of women revealed a family history of pica; 30.6% had pica in childhood and 13.2% suffered from polypica. Women with pica during pregnancy had similar age, pre-pregnancy body mass index (BMI), parity, neonatal birth weight and gestational age compared with non-pica mothers, although maternal haemoglobin concentration was lower in women with pica than in non-pica mothers (p = 0.0001). PMID- 22296427 TI - Obstetric hysterectomy: three technical measures. PMID- 22296428 TI - A demographic study to profile non-attenders at a gynaecology outpatient clinic. AB - Missed outpatient appointments result in the inefficient utilisation of resources and have secondary effects on the health of the non-attenders, as well as on other patients who have to wait longer for their appointments. The first part of the study involved retrospective analysis of trends of non-attendance based on a computerised database of all gynaecology appointments over 12 months. The second comprised a prospective case-control study in which women who missed their gynaecology outpatient appointments (index cases) over 2 months were compared with patients who attended the same clinics matched for indication for referral (control cases). The overall non-attendance rate over 12 months was 16.1%, of whom 42% were recurrent non-attenders. Data from 105 defaulters were compared with 105 non-defaulters who attended the same clinics. Defaulters were significantly younger, single or separated and were more likely to be 'follow ups' rather than new cases (all p < 0.05). Longer intervals between the appointment letter and actual appointment date was significantly related to non attendance (p = 0.01) and there was a trend to a greater degree of smoking and alcohol ingestion in the defaulter group (p = 0.059). Comparison of other variables such as severity of symptoms, parity, source of referral and fluency of English did not reach statistical significance (p > 0.05). This prospective study has demonstrated certain profiles which are common to defaulters and which can be used to develop strategies to minimise non-attendance. Examples include reducing the time interval between sending the appointment letter and actual appointment date and selectively over-booking younger, single women who smoke. PMID- 22296429 TI - Menarcheal and pubertal development and determining factors among schoolgirls in Kumasi, Ghana. AB - To determine menarcheal and pubertal ages and possible factors responsible for current pubertal trends in Kumasi, Ghana, a cross-sectional study was conducted among 720 urban and rural Kumasi 7-17-year-old schoolgirls and their mothers in 2008. Heights and weights were measured and additional information obtained by survey. Mantel-Haenzsel, chi(2), ordered logistic regression and probit analyses were used to analyse the data collected. With 40.42% menarcheal prevalence, median menarcheal ages were significantly different: 12.37 +/- 1.48 years urban and 13.41 +/- 2.25 years rural; 12.89 +/- 1.93 years, overall. Obesity (OR = 2.57; p = 0.033) and high socioeconomic status (OR = 2.12; p = 0.008) were predictors of early menarche, while a younger mother was protective against early menarche (OR = 0.32; p = 0.039). Age at menarche among Kumasi schoolgirls has dropped 0.76 years since it was last determined among similarly aged girls in 1986, declining at a rate of about 0.32 years/decade. The predicting factors provide an important opportunity for intervention through school curricula and targeted education of adolescents. PMID- 22296430 TI - Does current contraceptive choice correspond with user satisfaction? AB - A contraceptive method that suits an individual's needs may be more consistently used leading to greater user satisfaction. We therefore wanted to investigate whether a woman's current contraceptive choice corresponded with qualities identified by women as important. An anonymous survey was completed by women in their reproductive years, living in the North East of England, before seeing a healthcare professional. A total of 177 English-speaking women, who were sexually active and of reproductive age, completed questionnaires giving a response rate of 54%. A correlation was found between the current contraceptive used and the previously stated qualities felt to be important when choosing a method (p = 0.034, chi(2)-test). Similarly, a relationship was found between the current contraceptive method and reasons stated against choosing a contraceptive (p = 0.002, chi(2)-test). Overall, British women are generally satisfied with their chosen contraceptive method. PMID- 22296431 TI - Pre-sampling ultrasound evaluation and assessment of the tissue yield during sampling improves the diagnostic reliability of office endometrial biopsy. AB - We evaluated the implementation of a strict procedure for endometrium biopsy, including pre-sampling ultrasound examination and assessment of the tissue yield during sampling, in 257 consecutive women with abnormal bleeding. The tissue yield was assessed during sampling and scored from 1 to 4. The median endometrial thickness as measured by ultrasound was 5.0 mm, 5.1 mm, 10.0 mm and 18.7 mm for a tissue yield score of 1, 2, 3 and 4, respectively. The median endometrial thickness at ultrasound and the median tissue yield score was 18.3 mm and score 4 in the endometrial cancer cases, compared with 3.9 mm and score 1, and 14.8 mm and score 3 in the case of endometrial atrophy and hyperplasia, respectively; and 11.5 mm and score 2 in endometrial polyp cases. Overall, 12 cancers were diagnosed. No endometrial cancer was diagnosed during follow-up (median 447 days). A strict office endometrial biopsy procedure contributes to the diagnostic reliability for intracavitary pathology. PMID- 22296432 TI - A review of smoking cessation services in women attending colposcopy clinics in Scotland. AB - The most common reason for women being referred to colposcopy clinics is an abnormal smear suggesting pre-cancerous change within the cervix. It has been demonstrated that in women with low-grade lesions, smoking cessation led to a reduction in size of the cervical lesion over a 6-month period. Smoking is also recognised as an independent risk factor for treatment failure of cervical intraepithelial neoplasia. As 'stop smoking' services have become an integral part of the colposcopy clinic at St John's Hospital, Livingston, a national survey was undertaken. The aim of the survey was to establish what smoking cessation information, advice and support is available in colposcopy clinics throughout Scotland, and if staff had attended standardised training on raising the issue of smoking. The study demonstrated that 52% of colposcopy clinics in Scotland always establish smoking status but only 37% of clinics discuss the benefits of smoking cessation in relation to abnormal cervical smears. There was inaccurate and inconsistent written and verbal advice given on the benefits of cessation and whether women should cut down or stop smoking completely. The majority of staff had not attended standardised training on how to raise the issue of smoking and very few clinics have established referral pathways for smoking cessation support. PMID- 22296433 TI - Assessment of sexuality after hysterectomy using the Female Sexual Function Index. AB - The present study aimed at assessing sexuality after hysterectomy using the Female Sexual Function Index (FSFI). A telephone survey was conducted among women 1 year after a hysterectomy for benign cause. The FSFI and a general questionnaire containing personal and partner sociodemographic data were applied. A total of 100 sexually active women participated. Bilateral oophorectomy was performed among 41%. Upon survey, 63% were on hormone therapy (HT) and 2% on psychotropic drugs. Regarding the partner (n = 100), 32% abused alcohol; 11% had erectile dysfunction; 67% premature ejaculation and 11% were unfaithful. Total FSFI score was 19.4 +/- 3.6 (median 19.8) and for the domains: 3.2 +/- 0.9 (desire); 3.2 +/- 0.9 (arousal); 3.1 +/- 0.6 (lubrication); 3.1 +/- 0.7 (orgasm); 3.5 +/- 1.1 (satisfaction) and 3.2 +/- 1.2 (pain/dyspareunia). All women displayed sexual dysfunction (total FSFI score <= 26.55). A total of 53% presented FSFI scores equal to or below the calculated median for the series. Logistic regression determined that among women who had had a hysterectomy, male premature ejaculation was related to an overall poorer female sexual function (lower total FSFI scorings), whereas sometime oral contraceptive use decreased this risk. Age (female or male) and male sexual dysfunction were factors related to lower individual FSFI domain scores. PMID- 22296434 TI - Hermansky-Pudlak syndrome: management of a rare bleeding disorder in a twin pregnancy. PMID- 22296435 TI - Laparoscopic adrenalectomy for phaeochromocytoma in a twin gestation. PMID- 22296436 TI - Splenic hamartoma in pregnancy. PMID- 22296437 TI - Crigler-Najjar syndrome II and pregnancy outcome. PMID- 22296438 TI - Intra-abdominal displacement of a Propess(r) (pessary) found at the time of caesarean section. PMID- 22296439 TI - Uterine preservation in necrotising fasciitis following caesarean section. PMID- 22296440 TI - Neo-adjuvant chemotherapy and radical surgery for stage 1B cervical cancer in pregnancy. PMID- 22296441 TI - Suction of the uterine tube into an intraperitoneal drain. PMID- 22296442 TI - A laparoscopic sacrohysteropexy to manage uterine prolapse after surgical failure via a vaginal approach. PMID- 22296443 TI - Idiopathic thrombocytopenic purpura managed by intravenous anti-D. PMID- 22296444 TI - A rare case of benign abdominal wall and pelvic metastasizing leiomyomas following hysterectomy. PMID- 22296445 TI - Pelvic tuberculosis mimicking ovarian carcinoma with adnexal mass and very high serum level of CA125. PMID- 22296446 TI - Fibrolamellar hepatocellular carcinoma metastatic to the ovary. PMID- 22296447 TI - Vaginal cancer following etoposide-containing chemotherapy for metastatic gestational trophoblastic tumour. PMID- 22296449 TI - SiteBinder: an improved approach for comparing multiple protein structural motifs. AB - There is a paramount need to develop new techniques and tools that will extract as much information as possible from the ever growing repository of protein 3D structures. We report here on the development of a software tool for the multiple superimposition of large sets of protein structural motifs. Our superimposition methodology performs a systematic search for the atom pairing that provides the best fit. During this search, the RMSD values for all chemically relevant pairings are calculated by quaternion algebra. The number of evaluated pairings is markedly decreased by using PDB annotations for atoms. This approach guarantees that the best fit will be found and can be applied even when sequence similarity is low or does not exist at all. We have implemented this methodology in the Web application SiteBinder, which is able to process up to thousands of protein structural motifs in a very short time, and which provides an intuitive and user-friendly interface. Our benchmarking analysis has shown the robustness, efficiency, and versatility of our methodology and its implementation by the successful superimposition of 1000 experimentally determined structures for each of 32 eukaryotic linear motifs. We also demonstrate the applicability of SiteBinder using three case studies. We first compared the structures of 61 PA IIL sugar binding sites containing nine different sugars, and we found that the sugar binding sites of PA-IIL and its mutants have a conserved structure despite their binding different sugars. We then superimposed over 300 zinc finger central motifs and revealed that the molecular structure in the vicinity of the Zn atom is highly conserved. Finally, we superimposed 12 BH3 domains from pro-apoptotic proteins. Our findings come to support the hypothesis that there is a structural basis for the functional segregation of BH3-only proteins into activators and enablers. PMID- 22296450 TI - A 15q24 microdeletion in transient myeloproliferative disease (TMD) and acute megakaryoblastic leukaemia (AMKL) implicates PML and SUMO3 in the leukaemogenesis of TMD/AMKL. AB - Transient myeloproliferative disorder (TMD) of the newborn and acute megakaryoblastic leukaemia (AMKL) in children with Down syndrome (DS) represent paradigmatic models of leukaemogenesis. Chromosome 21 gene dosage effects and truncating mutations of the X-chromosomal transcription factor GATA1 synergize to trigger TMD and AMKL in most patients. Here, we report the occurrence of TMD, which spontaneously remitted and later progressed to AMKL in a patient without DS but with a distinct dysmorphic syndrome. Genetic analysis of the leukaemic clone revealed somatic trisomy 21 and a truncating GATA1 mutation. The analysis of the patient's normal blood cell DNA on a genomic single nucleotide polymorphism (SNP) array revealed a de novo germ line 2.58 Mb 15q24 microdeletion including 41 known genes encompassing the tumour suppressor PML. Genomic context analysis of proteins encoded by genes that are included in the microdeletion, chromosome 21 encoded proteins and GATA1 suggests that the microdeletion may trigger leukaemogenesis by disturbing the balance of a hypothetical regulatory network of normal megakaryopoiesis involving PML, SUMO3 and GATA1. The 15q24 microdeletion may thus represent the first genetic hit to initiate leukaemogenesis and implicates PML and SUMO3 as novel components of the leukaemogenic network in TMD/AMKL. PMID- 22296451 TI - Importance of halogen...halogen contacts for the structural and magnetic properties of CuX2(pyrazine-N,N'-dioxide)(H2O)2 (X = Cl and Br). AB - The structural and magnetic properties of the newly crystallized CuX(2)(pyzO)(H(2)O)(2) (X = Cl, Br; pyzO = pyrazine-N,N'-dioxide) coordination polymers are reported. These isostructural compounds crystallize in the monoclinic space group C2/c with, at 150 K, a = 17.0515(7) A, b = 5.5560(2) A, c = 10.4254(5) A, beta = 115.400(2) degrees , and V = 892.21(7) A(3) for X = Cl and a = 17.3457(8) A, b = 5.6766(3) A, c = 10.6979(5) A, beta = 115.593(2) degrees , and V = 950.01(8) A(3) for X = Br. Their crystal structure is characterized by one-dimensional chains of Cu(2+) ions linked through bidentate pyzO ligands. These chains are joined together through OH...O hydrogen bonds between the water ligands and pyzO oxygen atoms and Cu-X...X-Cu contacts. Bulk magnetic susceptibility measurements at ambient pressure show a broad maximum at 7 (Cl) and 28 K (Br) that is indicative of short-range magnetic correlations. The dominant spin exchange is the Cu-X...X-Cu supersuperexchange because the magnetic orbital of the Cu(2+) ion is contained in the CuX(2)(H(2)O)(2) plane and the X...X contact distances are short. The magnetic data were fitted to a Heisenberg 1D uniform antiferromagnetic chain model with J(1D)/k(B) = -11.1(1) (Cl) and 45.9(1) K (Br). Magnetization saturates at fields of 16.1(3) (Cl) and 66.7(5) T (Br), from which J(1D) is determined to be -11.5(2) (Cl) and -46.4(5) K (Br). For the Br analog the pressure dependence of the magnetic susceptibility indicates a gradual increase in the magnitude of J(1D)/k(B) up to -51.2 K at 0.84 GPa, suggesting a shortening of the Br...Br contact distance under pressure. At higher pressure X-ray powder diffraction data indicates a structural phase transition at ~3.5 GPa. Muon-spin relaxation measurements indicate that CuCl(2)(pyzO)(H(2)O)(2) is magnetically ordered with T(N) = 1.06(1) K, while the signature for long-range magnetic order in CuBr(2)(pyzO)(H(2)O)(2) was much less definitive down to 0.26 K. The results for the CuX(2)(pyzO)(H(2)O)(2) complexes are compared to the related CuX(2)(pyrazine) materials. PMID- 22296455 TI - Development of an evidence-based protocol for care of pilonidal sinus wounds healing by secondary intent using a modified Reactive Delphi procedure. Part 2: methodology, analysis and results. AB - This is the second part of the article based on the thesis work for a Masters of Science in Wound Healing and Tissue Repair, Cardiff University, to develop an evidence-based protocol for the care of pilonidal sinus wounds (PSWs) healing by secondary intent, using a modified Reactive Delphi process. The sample included surgeons, clinic physicians, nurses and enterostomal therapy nurses experienced in the care of these wounds. Item generation involved an extensive review of the literature to identify key aspects of evidence-based wound care essential to wound healing, infected wounds and pilonidal wounds healing by secondary intent and drawing on clinical experience. The participants responded via an electronic Delphi website, using a 4-point Likert rating scale and a ranking system. Comments were invited. Feedback was provided to the participants at the end of each round, that included comments, consensus scores, content validity index and additional information that provided rationale and references, or minor revision if requested. This project successfully achieved the objectives, which were to identify the areas of care that negatively or positively influences healing of postoperative PSWs and to inform, educate and broaden the considerations regarding these factors for health care professionals. PMID- 22296457 TI - Characteristics and outcome of brachial plexus birth palsy in neonates. AB - AIM: To relate pregnancy characteristics to extent and reversibility of brachial plexus birth palsy (BPBP) in neonates. METHODS: Retrospective case-control study: newborns with a registered diagnosis of BPBP (n = 168) 1990-2005 were compared to data from a randomly selected control group (n = 1000). Characteristics were related to the level of injury, reversibility and outcome. RESULTS: Among 51,841 newborns, 168 cases with BPBP were found (incidence 3.2/1000 newborns/year). Extent and reversibility of lesion did not differ with respect to characteristics of mothers, foetuses or deliveries. Children with C5-C6 and C5-C6-C7 injuries had complete recovery in 86% and 38%, respectively. Global injuries (C5-Th1) always had permanent disability. Accelerators (foetal weight gain >35 g/day after 32 weeks of gestation) and foetuses with estimated weight deviation >= +22% at 32 weeks were at seven- and ninefold increased risk of BPBP. Parous women were at doubled risk as compared to nulliparous women. CONCLUSION: Maternal and foetal characteristics influence risk of BPBP, but not the extent of injury or reversibility of injury. Because of the high risk of permanent disability and modest risk of low Apgar or pH among newborns with BPBP, the recommendation of prompt delivery may need to be re-evaluated. PMID- 22296458 TI - Experimental and computational insights into the stabilization of low-valent main group elements using crown ethers and related ligands. AB - A series of tin(II) triflate and chloride salts in which the cations are complexed by either cyclic or acyclic polyether ligands and which have well characterized single-crystal X-ray structures are investigated using a variety of experimental and computational techniques. Mossbauer spectroscopy illustrates that the triflate salts tend to have valence electrons with higher s-character, and solid-state NMR spectroscopy reveals marked differences between superficially similar triflate and chloride salts. Cyclic voltammetry investigations of the triflate salts corroborate the results of the Mossbauer and NMR spectroscopy and reveal substantial steric and electronic effects for the different polyether ligands. MP2 and DFT calculations provide insight into the effects of ligands and substituents on the stability and reactivity of the low-valent metal atom. Overall, the investigations reveal the existence of more substantial binding between tin and chlorine in comparison to the triflate substituent and provide a rationale for the considerably increased reactivity of the chloride salts. PMID- 22296459 TI - Evoked otoacoustic emissions: an alternative test of auditory function in horses. AB - REASONS FOR PERFORMING STUDY: Deafness has been reported in horses due to a variety of causes and objective auditory assessment has been performed with brainstem auditory evoked potential testing. Evoked otoacoustic emission (OAE) tests are widely used in human patients for hearing screening, detecting partial hearing loss (including frequency-specific hearing loss) and monitoring cochlear outer hair cell function over time. OAE tests are noninvasive, quick and affordable. Two types of OAE are commonly used clinically: transient evoked OAEs (TEOAEs) and distortion product OAEs (DPOAEs). Detection of OAEs has not been reported and OAE testing has not been evaluated for auditory assessment in horses. OBJECTIVES: To investigate whether TEOAEs and DPOAEs can be recorded in horses, and to evaluate the use of human OAE screening protocols in horses with apparently normal hearing. METHODS: Sixteen systemically healthy horses with normal behavioural responses to sound were included. OAE testing was performed during general anaesthesia using commercially available equipment and the final outcome for each ear for the TEOAE test (after a maximum of 3 runs) and the DPOAE test (after one run) were compared. RESULTS: TEOAEs and DPOAEs can be recorded in horses. Using the chosen TEOAE protocol, 96% of ears achieved a pass. Seventy percent of ears passed DPOAE testing, despite all of these ears passing TEOAE testing. CONCLUSIONS: Using the chosen stimulus and analysis protocols, TEOAEs were recorded from most ears; however, a smaller proportion of ears passed the DPOAE protocol, suggesting that this may be overly stringent and require further optimisation in horses. POTENTIAL RELEVANCE: OAE testing is rapid and easily performed in anaesthetised horses. It provides frequency-specific information about outer hair cell function, and is a promising tool for audiological assessment in the horse; however, it has not been assessed in conscious or sedated animals. PMID- 22296460 TI - Aptamer-based optical biosensor for rapid and sensitive detection of 17beta estradiol in water samples. AB - Required routine monitoring of endocrine disrupting compounds (EDCs) in water samples, as posed by EPA Unregulated Contaminant Regulation (UCMR3), demands for cost-effective, reliable and sensitive EDC detection methods. This study reports a reusable evanescent wave aptamer-based biosensor for rapid, sensitive and highly selective detection of 17beta-estradiol, an EDC that is frequently detected in environmental water samples. In this system, the capture molecular, beta-estradiol 6-(O-carboxy-methyl)oxime-BSA, was covalently immobilized onto the optical fiber sensor surface. With an indirect competitive detection mode, samples containing different concentrations of 17beta-estradiol were premixed with a given concentration of fluorescence-labeled DNA aptamer, which highly specifically binds to 17beta-estradiol. Then, the sample mixture is pumped to the sensor surface, and a higher concentration of 17beta-estradiol leads to less fluorescence-labeled DNA aptamer bound to the sensor surface and thus to lower fluorescence signal. The dose-response curve of 17beta-estradiol was established and a detection limit was determined as 2.1 nM (0.6 ng mL(-1)). The high specificity and selectivity of the sensor were demonstrated by evaluating its response to a number of potentially interfering EDCs. Potential interference of real environmental sample matrix was assessed by spiked samples in several tertiary wastewater effluents. The sensor can be regenerated with a 0.5% SDS solution (pH 1.9) over tens of times without significant deterioration of the sensor performance. This portable sensor system can be potentially applied for on site real-time inexpensive and easy-to-use monitoring of 17beta-estradiol in environmental samples such as effluents or water bodies. PMID- 22296462 TI - Letters. Literature citations. PMID- 22296463 TI - Letters. Groundwater. PMID- 22296464 TI - Letters. atmospheric mixing. PMID- 22296466 TI - Letters. Alcohol fuel. PMID- 22296465 TI - Letters. atmospheric mixing. PMID- 22296468 TI - Currents. PMID- 22296467 TI - Letters. Marine pollution. PMID- 22296469 TI - Outlook. PMID- 22296470 TI - Regulatory alert: Acid rain. PMID- 22296471 TI - How clean gas is made from coal. PMID- 22296472 TI - Environmental assessment of Antarctic research. PMID- 22296473 TI - Organic-rich colloidal material in estuaries and its alteration by chlorination. PMID- 22296474 TI - Field comparison of polyurethane foam and Tenax-GC resin for high-volume air sampling of chlorinated hydrocarbons. PMID- 22296476 TI - The carbon-bond mechanism: a condensed kinetic mechanism for photochemical smog. PMID- 22296475 TI - Potential for changing phytoplankton growth in Lake Powell due to oil shale development. PMID- 22296477 TI - Determination of vehicle emission rates from roadways by mass balance techniques. PMID- 22296478 TI - Biodegradability of halogen-substituted diphenylmethanes. PMID- 22296479 TI - Gas-phase chemistry of clean air at 55.degree. N latitude. PMID- 22296480 TI - Low-molecular-weight aliphatic amines in exhaust from catalyst-equipped cars. PMID- 22296481 TI - Transformation of the mouse clonal cell line R846-DP8 by Mississippi River, raw, and finished water samples from Southeastern Louisiana. PMID- 22296482 TI - An experimental study of the effect of temperature upon aerosol charge state. PMID- 22296483 TI - Bromine accumulations in pine trees growing around bromine production plants. PMID- 22296484 TI - Removal of thiosulfate/sulfate from spent Stretford solution. PMID- 22296485 TI - Cadmium bioaccumulation assays. Their relationship to various ionic equilibria in Lake Superior water. PMID- 22296486 TI - Industry trends. PMID- 22296488 TI - New literature. PMID- 22296490 TI - The role of assisted manipulation in cognitive development. AB - OBJECTIVE: Motor experience plays a central role in cognitive development. Assistive technologies can thus provide augmentative manipulation for children with motor disabilities. This paper explores the use of robots to this end. METHOD: A revision of studies conducted with typically-developing children and children with disabilities regarding the use of robots is presented. This revision provides a description of the cognitive skills required and revealed by the child when using a robot. Opportunities for participation and exploration were identified and further research is discussed. RESULTS: Robots provide insight into the cognitive skills of children with motor disabilities. Robots also provide means for independent exploration and participation in learning and play activities. Integration of augmentative manipulation and communication increases interest and participation of children with disabilities. CONCLUSION: Children with disabilities can use augmentative manipulation systems to independently explore and interact with their environment. Children can use robots as tools providing them with opportunities to reveal and further develop their cognitive skills. Alternative access methods can increase access for children with severe motor disabilities. PMID- 22296491 TI - A turning point for natural product discovery--ESF-EMBO research conference: synthetic biology of antibiotic production. AB - Synthetic Biology is in a critical phase of its development: it has finally reached the point where it can move from proof-of-principle studies to real-world applications. Secondary metabolite biosynthesis, especially the discovery and production of antibiotics, is a particularly relevant target area for such applications of synthetic biology. The first international conference to explore this subject was held in Spain in October 2011. In four sessions on General Synthetic Biology, Filamentous Fungal Systems, Actinomyces Systems, and Tools and Host Structures, scientists presented the most recent technological and scientific advances, and a final-day Forward Look Plenary Discussion identified future trends in the field. PMID- 22296492 TI - Assessing the impact of deliberative processes on the views of participants: is it 'in one ear and out the other'? AB - BACKGROUND: Interest in citizens' juries for eliciting the views of the public to inform coverage decisions on new health technologies has grown. However, evaluative information, particularly regarding their short- and/or longer-term impact on participants' views is limited. As citizens' juries can be resource intensive, such information is required to make 'evidence-based' decisions about their use. OBJECTIVES: To assess the impact of citizens' juries on participants' preferences for the distribution of health care across populations over time. SETTING AND PARTICIPANTS: Two citizens' juries, involving a different representative sample of the public, were held. Participants completed identical questionnaires before (T1), directly after (T2) and 6 weeks following the jury (T3). Questionnaires comprised rating, ranking and choice-based questions related to four characteristics of competing patient populations (age, current health, life expectancy without treatment and health gain resulting from an intervention). Semi-structured telephone interviews were also conducted to explore the impact of the jury on participants' distributive preferences. Changes in responses to the self-administered survey over the three time points were assessed quantitatively, while interview questions were analysed using qualitative techniques. RESULTS: No significant differences in responses to rating questions were observed. Pre/post-jury changes in the rankings of two factors were statistically significant in one of the juries. However, in both juries, T1-T2 changes in responses to several of the choice-based questions reached statistical significance. The number was lower between T2 and T3, suggesting that jurors retained their views. According to findings from the interviews, jurors' views changed or were clarified through participation in the jury. CONCLUSIONS: There appears to be evidence suggesting that the views of individuals who participate in citizens' juries change as a result of the experience, and those 'informed' views are sustained. PMID- 22296493 TI - Cone beam computed tomography for percutaneous nephrolithotomy: initial evaluation of a new technology. AB - BACKGROUND AND PURPOSE: Cone beam CT (CBCT) is a novel imaging modality that combines the versatility of conventional C-arm imaging with the functionality of cross-sectional imaging. This is a pilot study to evaluate the capabilities of this new technology to obtain percutaneous access and for the immediate postoperative evaluation of residual fragments in percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: A retrospective analysis of all PCNL cases performed between April 2007 and November 2007 was performed. One urologist (NSS) and one radiologist (JFA) reviewed the studies postoperatively. Preoperative films were evaluated to see if CBCT influenced or improved percutaneous access. Postoperative films were evaluated that compared CBCT with conventional noncontrast CT to determine efficacy in finding postoperative stone fragments. Parameters of stone size, location, and quantity of fragments were compared. RESULTS: For preoperative access, CBCT was used in 52 cases of PCNL between April 2007 and November 2007. In eight of these cases, CBCT altered the percutaneous access. In postoperative evaluation, 26 cases had both CBCT and conventional CT for comparison. In 11 cases with residual stones, conventional CT identified a greater number of fragments, but these were less than 2 mm. The postoperative recommendation for a secondary procedure concurred in 22 of 26 studies. CONCLUSIONS: CBCT may provide advantages of improved preoperative imaging, which may result in better percutaneous access, and improved postoperative imaging, which allows surgeons to have "real-time" access to CT quality images. The intraoperative availability of these high quality tomographic images may obviate the need for other postoperative imaging and subsequent adjunctive procedures for residual fragments. PMID- 22296494 TI - Service user involvement in pre-registration mental health nurse education classroom settings: a review of the literature. AB - Service user involvement in pre-registration nurse education is now a requirement, yet little is known about how students engage with users in the classroom, how such initiatives are being evaluated, how service users are prepared themselves to teach students, or the potential influence on clinical practice. The aim of this literature review was to bring together published articles on service user involvement in classroom settings in pre-registration mental health nurse education programmes, including their evaluations. A comprehensive review of the literature was carried out via computer search engines and the Internet, as well as a hand search of pertinent journals and references. This produced eight papers that fitted the inclusion criteria, comprising four empirical studies and four review articles, which were then reviewed using a seven-item checklist. The articles revealed a range of teaching and learning strategies had been employed, ranging from exposure to users' personal stories, to students being required to demonstrate awareness of user perspectives in case study presentations, with others involving eLearning and assessment skills initiatives. This review concludes that further longitudinal research is needed to establish the influence of user involvement in the classroom over time. PMID- 22296495 TI - Genetic polymorphism of matrix metalloproteinases in breast cancer. AB - The family of human matrix metalloproteinases (MMPs) consists of 24 zinc- and calcium-dependent proteolytic enzymes. MMPs are divided into six subgroups, in terms of differences in the substrate specificity with structural domain architecture. These enzymes are involved in many physiological processes, such as skeletal development, wound healing, scar formation, as well as carcinogenesis. MMPs, fulfilling its function of degradation of extracellular matrix components, are involved in one of the stages of angiogenesis enabling the development, growth and spread of the primary tumor. Therefore, the search for the common polymorphic variants of MMPs, new genetic markers as prognostic factors in breast cancer progress seems to be understandable.The minireview presents the results of 19 case-control or prospective studies concerning the association of SNPs of genes encoding nine MMPs: MMP-1, -2, -3, -7, -8, -9, -12, -13, -21 with the breast cancer risk, progression and survival. PMID- 22296496 TI - Kinetics of bilirubin and liver enzymes is useful for predicting of liver graft versus-host disease. AB - Graft-versus-host disease (GVHD) is the most frequent complication after allogeneic hematopoietic cell transplantation. We analyzed the kinetics of bilirubin and liver enzymes in 47 cases with liver GVHD and in 47 cases without GVHD after allogeneic transplantation for various hematological malignancies. The duration of an liver GVHD episode (LGVHD) was defined as the interval from the point when the criteria of LGVHD were met to the decrease to < 2 upper normal limit (UNL) for aminotransferases or bilirubin < 34 MUmol/l for bilirubin. The imminent LGVHD episode was defined as the interval from the start of continuous increase (>= 3 consecutive rising values) of bilirubin and liver enzymes above UNL to the point of LGVHD diagnosis.The number of imminent LGVHD episodes, and median length in days were as follows: bilirubin (39;5), ALT(28;12), AST(9;12), GGTP(34;9), and ALP(13;14). Statisticallly significant associations between asymptomatic continuous increase of bilirubin, ALT, and GGTP and later liver GVHD manifestation were found (p=0.004, p=0.008, p=0.005, respectively). The asymptomatic continuous increase in bilirubin, ALT, and GGTP occurred at a median of 5, 12, and 9 days before liver GVHD episode, respectively. In the control group without GVHD, median levels of bilirubin and liver enzymes were within normal limits and no continuous increase was observed.Kinetics of bilirubin and liver enzymes is useful for predicting of liver GVHD. A continuous increase of bilirubin and/or ALT, GGTP before the standard liver GVHD criteria are met can be a sign of coming liver GVHD. PMID- 22296497 TI - Effect of ionizing radiation on acinar morphogenesis of human prostatic epithelial cells under three-dimensional culture conditions. AB - Homeostasis is maintained by the interplay of multiple factors that directly or indirectly regulate cell proliferation and cell death. Complex multiple interactions between cells and the extracellular matrix occur during acinar morphogenesis and changes in these might indicate carcinogenesis of cells from a normal to a malignant, invasive phenotype. In this study, the human prostatic epithelial cell line RWPE-1 was cultured under three-dimensional (3-D) culture conditions, and the effect of ionizing radiation on acinar morphogenesis and its association with autophagy were discussed. The results illustrated that formation of specific spheroid (acinar) structures was detectable under 3-D culture conditions. Radiation induced the disruption of acini in different cell models using either gene overexpression (Akt) or gene knock-down (Beclin 1 and ATG7). Introduction of Akt not only accelerated the growth of cells (i.e., caused the cells to manifest elongating and microspike-like structures that are obviously different from structures seen in wild-type RWPE-1 cells under two-dimensional conditions), but also changed their morphological characteristics under 3-D culture conditions. Knock-down of autophagy-related genes (Beclin 1 and ATG7) increased the radiosensitivity of cells under 3-D culture conditions, and cells died of non-apoptotic death after radiation. The results suggested that ionizing radiation may change the cell phenotype and the formation of acini. Additionally even the autophagy mechanism may play a role in these processes. PMID- 22296498 TI - Lack of association between Human Oxoguanine Glycosylase 1 (hOGG1) S326C polymorphism and the risk of gastric cancer: a meta-analysis. AB - Results from published studies on the association of Human Oxoguanine Glycosylase 1 (hOGG1) S326C genetic polymorphism with the risk of gastric cancer are inconsistent. We performed a meta-analysis to summarize the possible association. Eleven case-control studies including 2168 cases and 4058 controls were identified from electronic databases (Pubmed, Elsevier Science Direct, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and the Chinese database, Wanfang). No significant association between hOGG1 S326C genetic polymorphism and risk of gastric cancer was observed in the overall analysis. In the stratified analysis based on ethnicity, still no significant association was observed in Europeans, Asians, or Brazilians. This meta-analysis provided evidence that hOGG1 S326C genetic polymorphism was not associated with increased risk of gastric cancer. However, additional studies with large sample size and better study designs are warranted to verify our finding. PMID- 22296499 TI - RNA interference-mediated silencing of Stat5 induces apoptosis and growth suppression of hepatocellular carcinoma cells. AB - It has been reported that Stat5 is overexpressed in a variety of human cancer cell lines and primary tumors. Inhibition of Stat5 in tumor cell lines has been associated with growth suppression and induction of apoptosis. However, no one of published studies have investigated the expression and role of Stat5 in hepatocellular carcinoma. In this study, we used human hepatocellular carcinoma cell line SMMC7721 as a model to demonstrate that Stat5 was highly expressed in these cells. Next we showed that RNAi mediated Stat5 knockdown could inhibit the proliferation and induce the apoptosis of SMMC7721 cells in vitro. Furthermore, we demonstrated that Stat5 knockdown inhibited the growth and induced the apoptosis of SMMC7721 cells in xenografts in nude mice. Taken together, our in vitro and in vivo data suggest that Stat5 plays an important role in human hepatocellular carcinoma. Inhibition of Stat5 by RNAi holds promise to be a novel gene therapy vector for hepatocellular carcinoma. PMID- 22296500 TI - Expression of putative stem marker nestin and CD133 in advanced serous ovarian cancer. AB - It is hypothesized that "cancer stem cells" are responsible for the resistance to chemotherapy of cancer cells in ovarian cancers. The objective of the studies was to explore if the stem cell biomarkers could be used to predict the tumor chemotherapy-resistance in serous ovarian cancer patients. Expression of two putative stem cell markers CD133 and nestin, and vascular epithelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) were detected in 123 cases of advanced serous ovarian cancer specimens by immunohistochemistry. To estimate intra-tumoral microvessel density (MVD), CD34 immunostaining was also performed. CD133 and nestin were defined to be positive in 35.0% and 32.5% of the serous ovarian carcinoma tissues, respectively. It was observed that overexpression of nestin but not CD133 was associated with the cisplatin-based chemotherapy resistance and shorter overall survival of the patients, and nestin was found to be an independent prognostic factor. Moreover, positive nestin expression also correlated to increased expression of EGFR and VEGF, and elevated MVD in tumors. The results of this study suggest that serous ovarian cancers with high expression level of nestin represent an aggressive malignant phenotype associated with poor prognosis, and treatment targeted the nestin positive cancer cells might be a promising therapeutic strategy for this subgroups. PMID- 22296501 TI - Incidence of cutaneous malignant melanoma in the Czech Republic: the risks of sun exposure for adolescents. AB - The Czech Republic reported one of the highest incidence rate in cutaneous melanoma (CM) in Europe and because this incidence has been increasing, mainly among young people, the main goal of our study was to establish sun exposure behavior risk factors for CM formation and to evaluate whether the young generation of Czechs is exposed to a higher risk of CM than the older generation. A questionnaire-based case-control study was conducted. We obtained 978 completed questionnaires: 216 from patients with CM and 762 from healthy respondents. The healthy individuals were further divided to adolescents (n = 460) and older respondents (n = 302). Three logistic regression models were developed: 1. patients with CM vs. healthy older respondents, 2. adolescents vs. healthy older respondents, and 3. patients with CM vs. adolescents. The main risk factors for all three models were the number of sunburn episodes and the use of the sunscreen in the childhood. The most alarming results for adolescents included: all day sun exposure, including times of maximum risk (11 AM to 3 PM), inadequate use of sunscreen in adulthood, and frequent mountain holidays. Our results show that sun safety in the young generation is satisfactory, when the responsibility for sun exposure behavior is in the hands of their parents; however, when children become adolescents, they become immune to sun-safety and risk prevention campaigns and their behavior becomes much more risky. Our results further suggest the sun safety campaigns need to be modified in such a way as to have greater impact and influence on adolescent sun-risk behaviors. PMID- 22296502 TI - Epigenetic inactivation of the canonical Wnt antagonist secreted frizzled-related protein 1 in hepatocellular carcinoma cells. AB - Secreted Frizzled-related protein 1 (sFRP1), as one of most important Wnt antagonists, is frequently silenced by promoter hypermethylation in many types of tumor, including hepatocellular carcinoma (HCC). In this study, we aimed to investigate whether restoration of sFRP1 affected HCC metastatic behavior. sFRP1 mRNA expression and promoter methylation in HCC tissues and cell lines were examined using RT-PCR and methylation-specific PCR (MS-PCR), respectively. sFRP1 protein expression was assessed by Western Blot. We generated stable HCC cell line restoration of sFRP1 in HepG2 cells, which naturally do not express detectable sFRP1 mRNA. The effects of exogenous sFRP1 on HepG2 cell invasion were investigated using trans-well assay. Also the effects of sFRP1 re-expression on the beta-catenin/T-cell factor-dependent transcription activity was measured by luciferase assay.sFRP1 promoter methylation was frequently observed in HCC tissues (60%) and cell lines (75%). All samples with sFRP1 methylation showed down-regulation of sFRP1 expression in HCC cell lines. Demethylation treatment with 5-aza-20-deoxycytidine in HCC cells restored sFRP1 expression. Restoration of sFRP1 substantially impaired the invasive potentials of HepG2 cells. Moreover, exogenous sFRP1 caused significant decrease of beta-catenin/T-cell factor dependent transcription activity.These findings demonstrate that sFRP1 silencing due to promoter hypermethylation is a major event during tumorigenesis. sFRP1 is also a negative modulator of canonical Wnt signaling, which could contribute to metastasis in HCC progression, thus providing a possible therapeutic strategy against HCC. PMID- 22296503 TI - Evaluation of active breathing control-moderate deep inspiration breath-hold in definitive non-small cell lung cancer radiotherapy. AB - The purpose of this study is to evaluate the effect of Active Breathing Control moderate deep inspiration breath-hold (ABC-mDIBH) on tumor motion and critical organ doses in non-small cell lung cancer (NSCLC) radiotherapy. 23 patients with locally advanced NSCLC were included in the study. All patients were scanned at free breathing and ABC-mDIBH for radiation treatment planning. 3 separate treatment plans were generated for each patient including one plan with ABC-mDIBH and uniform margins, one plan with free breathing and uniform margins, and one plan with free breathing and 3-dimensional non-uniform margins determined by Cone Beam Computed Tomography (CBCT) and XVI Motion View (X-ray Volume Imaging, Elekta, UK). Critical organ dose-volumes and physical lung parameters were comparatively evaluated on 3 separate dose-volume histograms of each patient acquired from planning software. Individual tumor motion of each patient with and without ABC-mDIBH was documented and compared. Use of ABC-mDIBH resulted in statistically significant improvement in physical lung parameters of V20 (lung volume receiving >= 20 Gy) and mean lung dose (MLD) which are predictors of radiation pneumonitis (p<0.001). Reduction in spinal cord dose and tumor motion with ABC-mDIBH was also statistically significant (p<0.001). ABC-mDIBH increases normal lung tissue sparing in definitive NSCLC radiotherapy by improving physical lung parameters along with spinal cord dose reduction through exact tumor immobilization. The incorporation of ABC-mDIBH into NSCLC radiotherapy may have implications for potential margin reduction and dose escalation to improve treatment outcomes. PMID- 22296504 TI - Transcription of promoter from the human APRIL gene regulated by Sp1 and NF-kB. AB - A proliferation-inducing ligand (APRIL) which stimulates the cell proliferation is abundantly expressed in colorectal cancer (CRC) tumors. In this report, the promoter region of the APRIL gene was determined and the major transcription factor was investigated for the first time. Deletion analysis of 5'-flanking region of the human APRIL gene and transient transfection revealed that a 538 bp region (from -1539 to -1001) was essential for promoter activation of the APRIL gene. The data from electrophoretic mobility shift assays (EMSA) indicated that the 538 bp promoter region was responsive to the specificity protein 1 (Sp1) and nuclear factor kappa B (NF-kB). Overexpression of Sp1 or NF-kB increased the activity of the APRIL promoter. Mithramycin A (inhibitor of Sp1) and Bay11-7082 (inhibitor of NF-kB) exhibited an inhibitory activity to APRIL promoter. Our results will benefit to the APRIL gene regulation investigation and contribute to discover new drug target for the APRIL gene therapy of CRC. PMID- 22296505 TI - Photocatalytic disinfection of bacterial pollutants using suspended and immobilized TiO2 powders. AB - The photocatalytic disinfection of Enterobacter cloacae and Enterobacter coli using microwave (MW), convection hydrothermal (HT) and Degussa P25 titania was investigated in suspension and immobilized reactors. In suspension reactors, MW treated TiO(2) was the most efficient catalyst (per unit weight of catalyst) for the disinfection of E. cloacae. However, HT-treated TiO(2) was approximately 10 times more efficient than MW or P25 titania for the disinfection of E. coli suspensions in surface water using the immobilized reactor. In immobilized experiments, using surface water a significant amount of photolysis was observed using the MW- and HT-treated films; however, disinfection on P25 films was primarily attributed to photocatalysis. Competitive action of inorganic ions and humic substances for hydroxyl radicals during photocatalytic experiments, as well as humic substances physically screening the cells from UV and hydroxyl radical attack resulted in low rates of disinfection. A decrease in colony size (from 1.5 to 0.3 mm) was noted during photocatalytic experiments. The smaller than average colonies were thought to occur during sublethal (*)OH and O(2)(*-) attack. Catalyst fouling was observed following experiments in surface water and the ability to regenerate the surface was demonstrated using photocatalytic degradation of oxalic acid as a model test system. PMID- 22296506 TI - Timing is everything: anticipatory stress dynamics among cortisol and blood pressure reactivity and recovery in healthy adults. AB - Psychological states of anticipation modulate biological stress responsivity. While researchers generally investigate how subjective distress corresponds to the magnitude of stress reactivity, physiological recovery after acute stressors must also be considered when investigating disease vulnerabilities. This study assessed whether anticipatory stress would correspond to stress reactivity and recovery of salivary cortisol and blood pressure levels in response to a well validated psychosocial stressor. Thirty participants (63% female; mean +/- SEM age 45.4 +/- 2.12 years) were exposed to the Trier Social Stress Test (TSST) consisting of a public speech and mental arithmetic. Ten salivary cortisol samples and systolic and diastolic blood pressure recordings were collected at time points spanning 50 min before and up to 50 min after stress exposure. These data were transformed into parameters representing stress reactivity (area under the curve) and stress recovery (percent change). The Primary Appraisal Secondary Appraisal scale assessed anticipatory stress before exposure to the TSST. Our results revealed that increased anticipatory stress predicted increased stress reactivity for cortisol (p = 0.009) but not blood pressure. For stress recovery, increased anticipatory stress predicted greater decrements of cortisol concentration (p = 0.015) and blood pressure (p = 0.039), even when controlling for total systemic "output" by incorporating baseline activity. This efficient shutdown of stress responses would have otherwise been ignored by solely investigating reactive increases. These findings underscore the importance of measuring multiple dynamic parameters such as recovery when investigating physiological stress response patterns as a function of psychosocial factors. PMID- 22296507 TI - Seasonal variability in the fertilization rate of women undergoing assisted reproduction treatments. AB - The objective of this study was to evaluate whether seasonality affects human assisted reproduction treatment outcomes. For this, 1932 patients undergoing intracytoplasmic sperm injection (ICSI) were assigned to a season group according to the day of oocyte retrieval: winter (n = 435), spring (n = 444), summer (n = 469) or autumn (n = 584). Analysis of variance was used to compare the ICSI outcomes. The fertilization rate was increased during the spring (winter: 67.9%, spring: 73.5%, summer: 68.7% and autumn: 69.0%; p < 0.01). In fact, a nearly 50% increase in the fertilization rate during the spring was observed (odds ratio 1.45, confidence interval 1.20-1.75; p < 0.01). The oestradiol concentration per number of oocytes was significantly higher during the spring (winter: 235.8 pg/mL, spring: 282.1 pg/mL, summer: 226.1 pg/mL and autumn: 228.7 pg/mL; p = 0.030). This study demonstrates a seasonal variability in fertilization after ICSI, where fertilization is higher during the spring than at any other time. PMID- 22296508 TI - Prognostic factors, course, and outcome of depression among older primary care patients: the PROSPECT study. AB - OBJECTIVES: We sought to examine whether there are patterns of evolving depression symptoms among older primary care patients that are related to prognostic factors and long-term clinical outcomes. METHOD: Primary care practices were randomly assigned to Usual Care or to an intervention consisting of a depression care manager offering algorithm-based depression care. In all, 599 adults 60 years and older meeting criteria for major depression or clinically significant minor depression were randomly selected. Longitudinal analysis via growth curve mixture modeling was carried out to classify patients according to the patterns of depression symptoms across 12 months. Depression diagnosis determined after a structured interview at 24 months was the long-term clinical outcome. RESULTS: Three patterns of change in depression symptoms over 12 months were identified: high persistent course (19.1% of the sample), high declining course (14.4% of the sample), and low declining course (66.5% of the sample). Being in the intervention condition was more likely to be associated with a course of high and declining depression symptoms than high and persistent depression symptoms (OR = 2.53, 95% CI [1.01, 6.37]). Patients with a course of high and persistent depression symptoms were much more likely to have a diagnosis of major depression at 24 months compared with patients with a course of low and declining depression symptoms (adjusted OR = 16.46, 95% CI [7.75, 34.95]). CONCLUSION: Identification of patients at particularly high risk of persistent depression symptoms and poor long-term clinical outcomes is important for the development and delivery of interventions. PMID- 22296509 TI - Combined effects of pi-pi stacking and hydrogen bonding on the (N1) acidity of uracil and hydrolysis of 2'-deoxyuridine. AB - M06-2X/6-31+G(d,p) is used to study the simultaneous effects of pi-pi stacking interactions with phenylalanine (modeled as benzene) and hydrogen bonding with small molecules (HF, H(2)O, and NH(3)) on the N1 acidity of uracil and the hydrolytic deglycosylation of 2'-deoxyuridine (dU) (facilitated by fully (OH(-)) or partially (HCOO(-)...H(2)O) activated water). When phenylalanine is complexed with isolated uracil, the proton affinity of all acceptor sites significantly increases (by up to 28 kJ mol(-1)), while the N1 acidity slightly decreases (by ~6 kJ mol(-1)). When small molecules are hydrogen bound to uracil, addition of the phenylalanine ring can increase or decrease the acidity of uracil depending on the number and nature (acidity) of the molecules bound. Furthermore, a strong correlation between the effects of pi-pi stacking on the acidity of U and the dU deglycosylation reaction energetics is found, where the hydrolysis barrier can increase or decrease depending on the nature and number of small molecules bound, the nucleophile considered (which dictates the negative charge on U in the transition state), and the polarity of the (bulk) environment. These findings emphasize that the catalytic (or anticatalytic) role of the active-site aromatic amino acid residues is highly dependent on the situation under consideration. In the case of uracil-DNA glycosylase (UNG), which catalyzes the hydrolytic excision of uracil from DNA, the type of discrete hydrogen-bonding interactions with U, the nature of the nucleophile, and the anticipated weak, nonpolar environment in the active site suggest that phenylalanine will be slightly anticatalytic in the chemical step, and therefore experimentally observed contributions to catalysis may entirely result from associated structural changes that occur prior to deglycosylation. PMID- 22296510 TI - Self-assembly of doublets from flattened polymer colloids. AB - Bottom-up fabrication methods are used to assemble strong yet flexible colloidal doublets. Part of a spherical particle is flattened, increasing the effective interaction area with another particle having a flat region. In the presence of a moderate ionic strength, the flat region on one particle will preferentially "bond" to a flat region on another particle in a deep (>=10 kT) secondary energy minimum. No external field is applied during the assembly process. Under the right conditions, the flat-flat bonding strength is >=10* that of a sphere-sphere interaction. Not only can flat-flat bonds be quite strong, but they are expected to remain freely rotatable and flexible, with negligible energy barriers for rotation because particles reside in a deep secondary energy minimum with a ~20 30 nm layer of fluid between the ~1 MUm radius particles. We present a controlled technique to flatten the particles at room temperature, the modeling of the interparticle forces for flattened spheres, and the experimental data for the self-assembly of flat-flat doublets. PMID- 22296511 TI - Highly selective cysteine detection and bioimaging in zebrafish through emission color change of water-soluble conjugated polymer-based assay complex. AB - A new concept for rapid, label-free cysteine sensing method is proposed via possible naked eye-detection of red-to-blue emission color change. Intermolecular exciton migration in conjugated polyelectrolyte-based assay complex is adopted to enhance selectivity and sensitivity for cysteine sensing by formation and dissociation of polymer-Hg(2+)-thymine assay complex in the absence and presence of cysteine, respectively. The assay complex shows red emission due to cooperative aggregation of conjugated polyelectrolyte, thymine, and Hg(2+). Upon exposure to cysteine, the assay complex dissociates into individual molecules showing transparent, blue-emitting solution, because cysteine extracts Hg(2+) from the assay complex via more favorable binding between cysteine and Hg(2+). PMID- 22296512 TI - Aripiprazole in bipolar depression: a pooled, post-hoc analysis by severity of core depressive symptoms. AB - OBJECTIVE: This post-hoc analysis of pooled data from two similarly designed trials assessed the impact of aripiprazole monotherapy vs. placebo on treatment outcomes based on baseline severity of core depressive symptoms in patients with bipolar I disorder. METHODS: Patients were classified as severely depressed (Bech 6 Total score > 15) or less severely depressed (Bech-6 Total score < 15). Efficacy was assessed by mean changes in Montgomery-Asberg Depression Rating Scale (MADRS) Total and MADRS-6 subscale scores from baseline to endpoint using a mixed model repeated measures analysis. RESULTS: A total of 133 patients (n = 62 on active aripiprazole) were classified as severely depressed and 612 patients (n = 309 aripiprazole) as less severely depressed. At endpoint, the mean MADRS Total score reduction for severely depressed patients receiving aripiprazole compared with placebo was -19.4 vs. -15.4 (P = 0.14), whereas MADRS-6 subscale score reduction for patients receiving aripiprazole compared with placebo was -13.8 vs. -10.3 (P = 0.07). Adverse event profiles were similar between the two severity groups. CONCLUSIONS: Symptomatic improvements assessed here suggest that aripiprazole monotherapy at the doses studied may provide some improvements in core symptoms of depression in patients with bipolar I disorder who were more severely depressed. PMID- 22296513 TI - Childhood trauma and compulsive buying. AB - OBJECTIVE: Childhood trauma has been empirically associated with various types of self-regulatory difficulties in adulthood. However, according to the extant literature, no study has examined relationships between various types of childhood trauma and compulsive buying behavior in adulthood. METHODS: Using a self-report survey methodology in a cross-sectional consecutive sample of 370 obstetrics/gynecology patients, we examined five types of childhood trauma before the age of 12 years (i.e. witnessing violence, physical neglect, emotional abuse, physical abuse, sexual abuse) in relationship to compulsive buying as assessed by the Compulsive Buying Scale (CBS). RESULTS: All forms of trauma demonstrated statistically significant correlations with the CBS. Using a linear regression analysis, both witnessing violence and emotional abuse significantly contributed to CBS scores. Further analyses indicated that race did not moderate the relationship between childhood trauma and compulsive buying. CONCLUSIONS: Findings indicate that various forms of childhood trauma are correlated with compulsive buying behavior, particularly witnessing violence and emotional abuse. PMID- 22296514 TI - Bipolar disorder: "pure" versus mixed depression over a 1-year follow-up. AB - OBJECTIVES: To compare two samples of Bipolar (BD) patients presenting "pure" (D) and mixed (Mx) depression to assess any difference in terms of clinical outcome, social functioning and quality of life during a 1-year follow-up. METHODS: A total of 114 depressed outpatients (HDRS > 13) were included. "Pure" depressed (D, n = 76) were divided from "mixed" depressed (Mx, n = 38) by the number of concomitant manic symptoms. All patients were evaluated by the Hamilton Depression Rating Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS), the Young Mania Rating Scale (YMRS), the Global Assessment of Functioning (GAF), the Social Adjustment Self-reported Scale (SASS) and the Quality of Life Scale (QoL), at baseline and after 1, 3, 6 and 12 months of treatment. RESULTS: Mx patients were significantly younger at the onset of BD. Manic features persisted significantly higher in Mx than in D patients all over the follow-up period. Axis I comorbidities had a negative impact on the course of social functioning over the medium term period, while Mx patients showed a faster improvement in social adjustment than "pure" depressed patients. CONCLUSIONS: Mixed features may persist relatively stable throughout a depressive episode, having a negative impact over clinical and functional outcome, but not on social adjustment. PMID- 22296515 TI - A 3D polar nanotubular coordination polymer with dynamic structural transformation and ferroelectric and nonlinear-optical properties. AB - A chiral coordination nanotube, [Cd(3)(BPT)(2)(H(2)O)(9)].2H(2)O (Cd-1; BPT = biphenyl-3,4',5-tricarboxylate), has been synthesized from achiral components and structurally characterized. It consists of homochiral channels based on right handed helical chains and shows an interdigitated interaction to give a chiral 3D network. The chiral nanotubular framework exhibts dynamic structural transformation upon removal of the guest molecules, and the polarity of this compound induces it to display both ferroelectric and nonlinear-optical properties. PMID- 22296516 TI - Efficacy of bortezomib, lenalidomide and dexamethasone (VRD) in secondary plasma cell leukaemia. PMID- 22296517 TI - Detailed analysis of peripheral blood natural killer cells in women with repeated IVF failure. AB - PROBLEM: To analyse the peripheral blood NK cells in women with repeated IVF failure (RIF) and a fertile control group to determine which parameters best differentiate the two populations. METHODS: Peripheral blood from the luteal phase of 171 women with RIF and 33 fertile controls was analysed by four-colour flow cytometry for NK cell concentration, subset differentiation and the activation marker CD69. RESULTS: Women with RIF had significantly increased NK cell numbers as determined by concentration (P < 0.05) and percentage of lymphocytes (P < 0.001), increased concentration of the CD56(dim) subtype (P < 0.05), and increased concentration of activated CD56(dim) CD69(+) cells (P = 0.0001). There was no correlation between any NK cell parameters with the length of infertility or number of embryo transfer cycles. CONCLUSIONS: Peripheral blood NK cell activity is significantly higher in women with RIF than in fertile controls. Future trials of immune therapy in women undergoing IVF should target those with high NK activity. PMID- 22296518 TI - The d'--d--d' vertical triad is less discriminating than the a'--a--a' vertical triad in the antiparallel coiled-coil dimer motif. AB - Elucidating relationships between the amino-acid sequences of proteins and their three-dimensional structures, and uncovering non-covalent interactions that underlie polypeptide folding, are major goals in protein science. One approach toward these goals is to study interactions between selected residues, or among constellations of residues, in small folding motifs. The alpha-helical coiled coil has served as a platform for such studies because this folding unit is relatively simple in terms of both sequence and structure. Amino acid side chains at the helix-helix interface of a coiled coil participate in so-called "knobs into-holes" (KIH) packing whereby a side chain (the knob) on one helix inserts into a space (the hole) generated by four side chains on a partner helix. The vast majority of sequence-stability studies on coiled-coil dimers have focused on lateral interactions within these KIH arrangements, for example, between an a position on one helix and an a' position of the partner in a parallel coiled-coil dimer, or between a--d' pairs in an antiparallel dimer. More recently, it has been shown that vertical triads (specifically, a'--a--a' triads) in antiparallel dimers exert a significant impact on pairing preferences. This observation provides impetus for analysis of other complex networks of side-chain interactions at the helix-helix interface. Here, we describe a combination of experimental and bioinformatics studies that show that d'--d--d' triads have much less impact on pairing preference than do a'--a--a' triads in a small, designed antiparallel coiled-coil dimer. However, the influence of the d'--d--d' triad depends on the lateral a'--d interaction. Taken together, these results strengthen the emerging understanding that simple pairwise interactions are not sufficient to describe side-chain interactions and overall stability in antiparallel coiled-coil dimers; higher-order interactions must be considered as well. PMID- 22296519 TI - Statistical optimization of simple culture conditions to produce biomass of an ochratoxigenic mould biocontrol yeast strain. AB - AIM: To maximize biomass production of an ochratoxigenic mould-controlling strain of Lachancea thermotolerans employing response surface methodology (RSM). METHODS AND RESULTS: Using Plackett-Burman screening designs (PBSD) and central composite designs (CCD), an optimized culture medium containing (g l(-1) ): fermentable sugars (FS), 139.2, provided by sugar cane molasses (CMz), (NH(4) )(2) HPO(4) (DAP), 9.0, and yeast extract (YE), 2.5, was formulated. Maximal cell concentration obtained after 24 h at 28 degrees C was 24.2 g l(-1) cell dry weight (CDW). The mathematical model obtained was validated in experiments performed in shaken-flask cultures and also in aerated bioreactors. Maximum yield and productivity values achieved were, respectively, of 0.23 g CDW/g FS in a medium containing (g l(-1) ): FS, 87.0; DAP, 7.0; YE, 1.0; and of 0.96 g CDW l( 1) h(-1) in a medium containing (g l(-1) ): FS, 150.8 plus DAP, 6.9. CONCLUSIONS: Optimized culture conditions for maximizing yeast biomass production determined in flask cultures were applicable at a larger scale. The highest yield values were attained in media containing relatively low-CMz concentrations supplemented with DAP and YE. Yeast extract would not be necessary if higher productivity is the aim. SIGNIFICANCE AND IMPACT OF THE STUDY: Cells of L. thermotolerans produced aerobically could be sustainably produced in a medium just containing cheap carbon, nitrogen and phosphorus sources. Response surface methodology allowed the fine-tuning of cultural conditions. PMID- 22296520 TI - Re: Urinary tract infections in children and the risk of ESRF. PMID- 22296522 TI - Gut bacteria in health and disease: a survey on the interface between intestinal microbiology and colorectal cancer. AB - A healthy human body contains at least tenfold more bacterial cells than human cells and the most abundant and diverse microbial community resides in the intestinal tract. Intestinal health is not only maintained by the human intestine itself and by dietary factors, but is also largely supported by this resident microbial community. Conversely, however, a large body of evidence supports a relationship between bacteria, bacterial activities and human colorectal cancer. Symbiosis in this multifaceted organ is thus crucial to maintain a healthy balance within the host-diet-microbiota triangle and accordingly, changes in any of these three factors may drive a healthy situation into a state of disease. In this review, the factors that sustain health or drive this complex intestinal system into dysbiosis are discussed. Emphasis is on the role of the intestinal microbiota and related mechanisms that can drive the initiation and progression of sporadic colorectal cancer (CRC). These mechanisms comprise the induction of pro-inflammatory and pro-carcinogenic pathways in epithelial cells as well as the production of (geno)toxins and the conversion of pro-carcinogenic dietary factors into carcinogens. A thorough understanding of these processes will provide leads for future research and may ultimately aid in development of new strategies for CRC diagnosis and prevention. PMID- 22296523 TI - Urea metal-organic frameworks as effective and size-selective hydrogen-bond catalysts. AB - A new urea-containing metal-organic framework (MOF) was synthesized to act as a heterogeneous catalyst. Ureas are well-known for self-recognition and aggregation behavior, resulting in loss of catalytic competency. The catalyst spatial isolation achievable in a porous MOF environment suggests a potentially general solution. The combination of a symmetrical urea tetracarboxylate strut, 4,4' bipyridine, and Zn(NO(3))(2).6H(2)O under solvothermal conditions afforded a new microporous MOF (NU-601). This material is indeed an effective hydrogen-bond donor catalyst for Friedel-Crafts reactions between pyrroles and nitroalkenes, whereas a homogeneous urea is much less competent. The higher rates of reaction of small substrates relative to larger ones with NU-601 strongly suggest that catalysis primarily occurs within the pores of this new material rather than on its exterior. To the best of our knowledge, this approach is the first example of specific engineering of successful hydrogen-bonding catalysis into a MOF material. PMID- 22296524 TI - Wound-healing potential of an ethanol extract of Carica papaya (Caricaceae) seeds. AB - Carica papaya L. (Linn) (Caricaceae) is traditionally used to treat various skin disorders, including wounds. It is widely used in developing countries as an effective and readily available treatment for various wounds, particularly burns. This study evaluated the wound-healing and antimicrobial activity of C. papaya seed extract. Ethanol extract of C. papaya seed (50 mg/kg/day) was evaluated for its wound-healing activity in Sprague-Dawley rats using excision wound model. Animals were randomly divided into four groups of six each (group 1 served as control, group 2 treated with papaya seed extract, group 3 treated with a standard drug mupirocin and papaya seed extract (1:1 ratio) and group 4 treated with a mupirocin ointment. Rate of wound contraction and hydroxyproline content were determined to assess the wound-healing activity of the seed extract. The group 2 animals showed a significant decrease in wound area of 89% over 13 days when compared with groups 1 (82%), 3 (86%) and 4 (84%) respectively. The hydroxyproline content was significantly higher with the granulation tissue obtained from group 2 animals which were treated with C. papaya seed extract. Histological analysis of granulation tissue of the group 2 animals showed the deposition of well-organized collagen. The extract exhibited antimicrobial activity against Salmonella choleraesuis and Staphylococcus aureus. Our results suggest that C. papaya promotes significant wound healing in rats and further evaluation for this activity in humans is suggested. PMID- 22296525 TI - Sibling relationships in individuals with Angelman syndrome: a comparative study. AB - OBJECTIVE: Investigating the impact of Angelman syndrome on the sibling relationship. METHODS: This study explored differences in sibling relationships between children with a typically-developing sibling (n = 55) and children with a sibling with Angelman syndrome (n = 44). Sibling relationships were compared on four factors and 16 sub-scales of the Sibling Relationship Questionnaire-Revised. RESULTS: Results showed significant differences in mean scores on each of the four factors (i.e. Warmth/Closeness, Conflict, Rivalry and Dominance/Nurturance) and most of the sub-scales. ANCOVAs showed that demographic variables (number of siblings, living in a two-parent vs single parent household, gender, participant's age, place of residence) did not influence significant differences in sibling relationships between the two groups. CONCLUSION: Having a brother or sister with Angelman syndrome may influence the way in which the sibling perceives the sibling relationship. This may have important implications for family-centred intervention for this population. PMID- 22296526 TI - Ratcheting up cancer potency estimates. AB - The current paradigm for cancer risk assessment in the United States (U.S.) typically requires selection of representative rodent bioassay dose-response data for extrapolation to a single cancer potency estimate for humans. In the absence of extensive further information, the chosen bioassay result generally is taken to be that which gives the highest extrapolated result from the "most sensitive" species or strain. The estimated human cancer potency is thus derived from an upper-bound value on animal cancer potency that is technically similar to an extreme value statistic. Thus additional information from further bioassays can only lead to equal or larger cancer potency estimates. We here calculate the size of this effect using the collected results of a large number of bioassays. Since many standards are predicated on the value of the cancer potency, this effect is undesirable in producing a strong counter-incentive to performing further bioassays. PMID- 22296527 TI - Making choices about medical interventions: the experience of disabled young people with degenerative conditions. AB - BACKGROUND: Current western policy, including the UK, advocates choice for service users and their families, taking greater control and being more involved in decision making. However, children's role in health decision making, especially from their own perspective, has received less research attention compared to doctors and parents' perspectives. OBJECTIVE: To explore the perspective and experiences of disabled young people with degenerative conditions as they face significant medical interventions and engage in decision-making processes. DESIGN AND METHODS: Findings from a longitudinal qualitative study of 10 young people (13-22 years) with degenerative conditions are reported. Individual semi-structured interviews were conducted with participants over 3 years (2007-2010); the paper reports data from all three interview rounds. Interviews focused on medical intervention choices the young people identified as significant. RESULTS: Although the young people in this study felt involved in the medical intervention choices discussed, findings demonstrate a complex and diverse picture of decision making. Results highlighted different decisional roles adopted by the young people, the importance of information heuristics and working with other people whilst engaging in complex processes weighing up different decisional factors. DISCUSSION: Young people's experiences demonstrate the importance of moving beyond viewing health choices as technical or rational decisions. How each young person framed their decision was important. Recognizing this diversity and the importance of emerging themes, such as living a normal life, independence, fear of decisions viewed as 'irreversible' and the role of parents and peers in decision making highlights that, there are clear practice implications including, active practitioner listening, sensitivity and continued holistic family working. PMID- 22296529 TI - Editorial. editorial policy changes. PMID- 22296530 TI - Letters. International engineering ethics projects. PMID- 22296532 TI - Currents. PMID- 22296531 TI - Letters. smog in melbourne? PMID- 22296533 TI - Outlook. PMID- 22296534 TI - Regulatory alert: regulation of coal mining. PMID- 22296535 TI - Kepone in the james river. PMID- 22296536 TI - Developing solutions to hazardous-waste problems. PMID- 22296539 TI - New literature. PMID- 22296537 TI - Determining volatile organics in water. PMID- 22296541 TI - Acoustical particle sizing device. PMID- 22296542 TI - An experimental study for low-NOx fluidized-bed coal combustor development. 1. Combustion under substoichiometric conditions. PMID- 22296543 TI - An experimental study for low-NOx fluidized-bed coal combustor development. 2. Performance of two-stage fluidized-bed combustion. PMID- 22296544 TI - Some etching studies of the microstructure and composition of large aluminosilicate particles in fly ash from coal-burning power plants. PMID- 22296545 TI - Total organic halogen as a parameter for the characterization of reclaimed waters: measurement, occurrence, formation, and removal. PMID- 22296546 TI - Virtual impactors: a theoretical study. PMID- 22296547 TI - Water vapor effect on photochemical ozone formation in a propylene-NOx-air system. PMID- 22296549 TI - Factors influencing the release of boron from coal ash materials. PMID- 22296548 TI - Fourier transform infrared spectroscopy for inorganic compound speciation. PMID- 22296550 TI - Some observations of organic constituents in rain above and below a forest canopy. PMID- 22296551 TI - Enrichment of trace elements in remote aerosols. PMID- 22296552 TI - Comparison of measured ozone in southeastern Virginia with computer predictions from a photochemical model. PMID- 22296553 TI - A new technique for the scanning electron microscopy of particles collected on membrane filters. PMID- 22296554 TI - Budgeting of polychlorinated biphenyl (PCB) fluxes in and out of Lake Superior. Comments. PMID- 22296555 TI - Budgeting of polychlorinated biphenyl (PCB) fluxes in and out of Lake Superior. Reply to comments. PMID- 22296556 TI - Dual-responsive magnetic core-shell nanoparticles for nonviral gene delivery and cell separation. AB - We present the synthesis of dual-responsive (pH and temperature) magnetic core shell nanoparticles utilizing the grafting-from approach. First, oleic acid stabilized superparamagnetic maghemite (gamma-Fe(2)O(3)) nanoparticles (NPs), prepared by thermal decomposition of iron pentacarbonyl, were surface functionalized with ATRP initiating sites bearing a dopamine anchor group via ligand exchange. Subsequently, 2-(dimethylamino)ethyl methacrylate (DMAEMA) was polymerized from the surface by ATRP, yielding dual-responsive magnetic core shell NPs (gamma-Fe(2)O(3)@PDMAEMA). The attachment of the dopamine anchor group on the nanoparticle's surface is shown to be reversible to a certain extent, resulting in a grafting density of 0.15 chains per nm(2) after purification. Nevertheless, the grafted NPs show excellent long-term stability in water over a wide pH range and exhibit a pH- and temperature-dependent reversible agglomeration, as revealed by turbidimetry. The efficiency of gamma Fe(2)O(3)@PDMAEMA hybrid nanoparticles as a potential transfection agent was explored under standard conditions in CHO-K1 cells. Remarkably, gamma Fe(2)O(3)@PDMAEMA led to a 2-fold increase in the transfection efficiency without increasing the cytotoxicity, as compared to polyethyleneimine (PEI), and yielded on average more than 50% transfected cells. Moreover, after transfection with the hybrid nanoparticles, the cells acquired magnetic properties that could be used for selective isolation of transfected cells. PMID- 22296557 TI - Impact of endothelial cells on 3D cultured smooth muscle cells in a biomimetic hydrogel. AB - For the development of vascular tissue engineering, the impact of endothelial cells (ECs) on smooth muscle cell (SMC) spreading, proliferation, and differentiation is explored in the current study using a coculture model. In this coculture model, SMCs were encapsulated in a biomimetic hydrogel based on methacrylated dextran-graft-lysine (Dex-MA-LA) and methacrylamide-modified gelatin (Gel-MA), and exposed to a monolayer of ECs. With EC coculture, SMC proliferation in 3D hydrogel was promoted at initial period, and the formation of denser cellular networks was enhanced. ECs dynamically modulated SMC phenotype by promoting a more contractile SMC phenotype initially (on day 2), indicated by the upregulated expression of contractile genes alpha-actin, calponin, smooth muscle myosin heavy chain (SM-MHC), and smoothelin; however, the onset of maximum expressions was delayed by ECs. Full differentiation of SMCs was not obtained even with EC coculture. Higher level of platelet-derived growth factor (PDGF)-BB and latent transforming growth factor (TGF)-beta1 were detected in medium of coculture. These biochemical cues together with the physical cue of tensional force within cellular networks may be responsible for the dynamic modulation of SMC phenotype in coculture. Synthesis of elastin was promoted by ECs at transcriptional level. The formation of denser cellular networks and synthesis of elastin suggest that coculture with ECs is a potential method to construct functional vessel media layer in vitro. PMID- 22296558 TI - Expression of the RNA recognition motif protein RBP10 promotes a bloodstream-form transcript pattern in Trypanosoma brucei. AB - When Trypanosoma brucei differentiates from the bloodstream form to the procyclic form, there are decreases in the levels of many mRNAs encoding proteins required for the glycolytic pathway, and the mRNA encoding the RNA recognition motif protein RBP10 decreases in parallel. We show that RBP10 is a cytoplasmic protein that is specific to bloodstream-form trypanosomes, where it is essential. Depletion of RBP10 caused decreases in many bloodstream-form-specific mRNAs, with increases in mRNAs associated with the early stages of differentiation. The changes were similar to, but more extensive than, those caused by glucose deprivation. Conversely, forced RBP10 expression in procyclics induced a switch towards bloodstream-form mRNA expression patterns, with concomitant growth inhibition. Forced expression of RBP10 prevented differentiation of bloodstream forms in response to cis-aconitate, but did not prevent expression of key differentiation markers in response to glucose deprivation. RBP10 was not associated with heavy polysomes, showed no detectable in vivo binding to RNA, and was not stably associated with other proteins. Tethering of RBP10 to a reporter mRNA inhibited translation, and halved the abundance of the bound mRNA. We suggest that RBP10 may prevent the expression of regulatory proteins that are specific to the procyclic form. PMID- 22296559 TI - Two new noncentrosymmetric (NCS) polar oxides: syntheses, characterization, and structure-property relationships in BaMTe2O7 (M = Mg2+ or Zn2+). AB - Two new noncentrosymmetric (NCS) polar oxides, BaMgTe(2)O(7) and BaZnTe(2)O(7), have been synthesized and characterized, with their crystal structures determined by single crystal X-ray diffraction. The iso-structural materials exhibit structures consisting of layers of corner-shared MgO(5) or ZnO(5), Te(6+)O(6), and Te(4+)O(4) polyhedra that are separated by Ba(2+) cations. The Te(4+) cation is found in a highly asymmetric and polar coordination environment attributable to its stereoactive lone-pair. The alignment of the individual TeO(4) polar polyhedra results in macroscopic polarity for BaMgTe(2)O(7) and BaZnTe(2)O(7). Powder second-harmonic generation (SHG) measurements revealed a moderate SHG efficiency of approximately 5 * KDP (or 200 * alpha-SiO(2)) for both materials. Piezoelectric charge constants of 70 and 57 pm/V, and pyroelectric coefficients of -18 and -10 MUC.m(-2).K(-1) were obtained for BaMgTe(2)O(7) and BaZnTe(2)O(7), respectively. Although the materials are polar, frequency dependent polarization measurements indicated that the materials are not ferroelectric, that is, the observed macroscopic polarization cannot be reversed. Infrared, UV-vis diffuse spectroscopy, and thermal properties were also measured. Crystal data: BaMgTe(2)O(7), orthorhombic, space group Ama2 (No. 40), a = 5.558(2) A, b = 15.215(6) A, c = 7.307(3) A, V = 617.9(4) A(3), and Z = 4; BaZnTe(2)O(7), orthorhombic, space group Ama2 (No. 40), a = 5.5498(4) A, b = 15.3161(11) A, c = 7.3098(5) A, V = 621.34(8) A(3), and Z = 4. PMID- 22296560 TI - UV released factors induce antioxidant defense in A375 cells. AB - UV light leads to release of different secretory factors from irradiated cells of which some of them have been characterized. We have reported earlier that cells exposed to the supernatant medium from irradiated cells were resistant to killing by some genotoxic agents. In this study, we present our finding that demonstrates DNA damage induced by UV or H(2)O(2) is lowered on prior exposure to the UV released factors (UVRF). Production of ROS in cells and lipid peroxidation was also lowered. It was found that treatment of unexposed cells with UVRF present in the supernatant medium altered the antioxidant defense activity in cells. Significant was the increase in catalase (CAT) and Cu-Zn superoxide dismutase (SOD) activity, whereas glutathione peroxidase (GPx) and reduced glutathione (GSH) levels remained unaffected. Cells exposed to UVRF prior to UV or H(2)O(2) treatment also experienced such upregulation; however, the remarkable increase in the GPx activity exhibited by these cells was not observed in cells exposed to H(2)O(2) or UV alone. It appears that exposure to UVRF tinkered with antioxidant defense in cells to facilitate its proliferation upon assault by an agent that can produce oxidative damage. PMID- 22296561 TI - Impact of adrenal versus ovarian androgen ratio on signs and symptoms of polycystic ovarian syndrome. AB - The aim of this study was to examine the effect of adrenal versus ovarian androgen (dehydroepiandrosterone sulfate/total testosterone [DHEAS/TT]) on clinical presentation and related metabolic disturbances in Turkish women with polycystic ovarian syndrome (PCOS). Two hundred eighty PCOS cases were taken into the study. For all cases, the DHEAS/TT ratio was calculated. The median value of this ratio was 4.40. Patients with an androgen ratio lower than 4.40 were included in Group 1 and cases with a ratio higher than 4.40 were Group 2. The two groups were compared in terms of hormonal, biochemical and clinical parameters. Body mass index and waist circumference were lower, the Ferriman-Gallwey score was higher and the cycle length was shorter in Group 2. High DHEAS level was associated with better lipid profiles and lower levels of inflammatory markers, meaning good metabolic control in these women, in spite of increased hirsutism rates. In patients with PCOS, both androgens are usually high in proportion to each other. Therefore, it would be more meaningful to use the DHEAS/TT ratio for an assessment of the metabolic and phenotypic effects of PCOS. PMID- 22296562 TI - Embryonic fibroblasts enable the culture of primary ovarian follicles within alginate hydrogels. AB - Hydrogel-encapsulating culture systems support the consistent growth of ovarian follicles from various species, such as mouse, non-human primate, and human; however, further innovations are required for the efficient production of quality oocytes from early-stage follicles. In this report, we investigated the coculture of mouse ovarian follicles with mouse embryonic fibroblasts (MEFs), commonly used as feeder cells to promote the undifferentiated growth of embryonic stem (ES) cells, as a means to provide the critical paracrine factors necessary for follicle survival and growth. Follicles were encapsulated within alginate hydrogels and cocultured with MEFs for 14 days. Coculture enabled the survival and growth of early secondary (average diameter of 90-100 MUm) and primary (average diameter of 70-80 MUm) follicles, which developed antral cavities and increased in diameter to 251-347 MUm. After 14 days, follicle survival ranged from 70% for 100-MUm follicles to 23% for 70-MUm follicles. Without MEF coculture, all follicles degenerated within 6-10 days. Furthermore, 72%-80% of the oocytes from surviving follicles underwent germinal vesicle breakdown (GVBD), and the percentage of metaphase II (MII) eggs was 41%-69%. Medium conditioned by MEFs had similar effects on survival, growth, and meiotic competence, suggesting a unidirectional paracrine signaling mechanism. This advancement may facilitate the identification of critical factors responsible for promoting the growth of early-stage follicles and lead to novel strategies for fertility preservation. PMID- 22296563 TI - Coeliac disease and risk of venous thromboembolism: a nationwide population-based case-control study. PMID- 22296564 TI - Prinzmetal angina in the differential diagnosis of syncope. AB - Prinzmetal (variant) angina may be associated with cardiac arrhythmias that can deteriorate to fatal ventricular arrhythmias. We present 2 patients with syncope where vasospastic angina and severe ventricular arrhythmias were found to be responsible for the syncopal episodes. PMID- 22296565 TI - An exploration of the experience of mental health service users when they decide they would like to change or withdraw from prescribed medications. AB - This paper reports on a collaborative research project initiated by service user representatives and led by clinicians from the mental health service in Derbyshire. The study explored the experiences of mental health service users when they either changed or terminated their use of mental health-related medications. Three focus groups were conducted with mental health service users from across the county. An inductive thematic analysis identified six key themes, three of which are reported here: the 'two faces' of service provision, describing the positive and negative experiences of services; the general practice/mental health divide, relating to the lack of continuity between the two services; and becoming an informed service user, where participants discussed the importance of seeking information. It is important that mental health professionals always consider presenting their 'best face' to service users, and facilitate the prescribing process with general practitioners. The findings also highlight the potential for supporting service users in using different sources of information to become more informed about medication. PMID- 22296566 TI - Role of solvation dynamics and local ordering of water in inducing conformational transitions in poly(N-isopropylacrylamide) oligomers through the LCST. AB - Conformational transitions in thermo-sensitive polymers are critical in determining their functional properties. The atomistic origin of polymer collapse at the lower critical solution temperature (LCST) remains a fundamental and challenging problem in polymer science. Here, molecular dynamics simulations are used to establish the role of solvation dynamics and local ordering of water in inducing conformational transitions in isotactic-rich poly(N-isopropylacrylamide) (PNIPAM) oligomers when the temperature is changed through the LCST. Simulated atomic trajectories are used to identify stable conformations of the water molecule network in the vicinity of polymer segments, as a function of the polymer chain length. The dynamics of the conformational evolution of the polymer chain within its surrounding water molecules is evaluated using various structural and dynamical correlation functions. Around the polymer, water forms cage-like structures with hydrogen bonds. Such structures form at temperatures both below and above the LCST. The structures formed at temperatures above LCST, however, are significantly different from those formed below LCST. Short oligomers consisting of 3, 5, and 10 monomer units (3-, 5-, and 10-mer), are characterized by significantly higher hydration level (water per monomer ~ 16). Increasing the temperature from 278 to 310 K does not perturb the structure of water around the short oligomers. In the case of 3-, 5-, and 10-mer, a distinct coil-to-globule transition was not observed when the temperature was raised from 278 to 310 K. For a PNIPAM polymer chain consisting of 30 monomeric units (30 mer), however, there exist significantly different conformations corresponding to two distinct temperature regimes. Below LCST, the water molecules in the first hydration layer (~12) around hydrophilic groups arrange themselves in a specific ordered manner by forming a hydrogen-bonded network with the polymer, resulting in a solvated polymer acting as hydrophilic. Above LCST, this arrangement of water is no longer stable, and the hydrophobic interactions become dominant, which contributes to the collapse of the polymer. Thus, this study provides atomic-scale insights into the role of solvation dynamics in inducing coil-to globule phase transitions through the LCST for thermo-sensitive polymers like PNIPAM. PMID- 22296567 TI - In-hospital outcomes and cost assessment between bipolar versus monopolar transurethral resection of the prostate. AB - PURPOSE: We compared the in-hospital outcomes between bipolar and monopolar transurethral resection of the prostate (B-TURP and M-TURP, respectively) on a real-world practice using a large database. PATIENTS AND METHODS: Patients who underwent TURP were extracted from the Diagnosis Procedure Combination database, which is a case-mix administrative claims database in Japan. TURP procedures were classified into M-TURP and B-TURP groups according to intraoperative use or nonuse of D-sorbitol solution, respectively, which is the only nonelectrolyte bladder irrigation fluid for M-TURP available in Japan. To exclude causality among autologous and homologous transfusion events, we confined eligible hospitals to those in which no autologous blood preparation was undertaken for TURP and whose annual surgical caseloads were 15 cases or more. Multivariate analyses were conducted for homologous transfusion, postoperative complications, operative time, postoperative length of stay, and total costs. RESULTS: There were 5155 M-TURP and 1531 B-TURP patients identified. The results for M-TURP vs B TURP (effect sizes were evaluated with reference to M-TURP) were 2.3% vs 1.3% for transfusion (odds ratio [OR]=0.54; P=0.013), 3.3% vs 1.7% for postoperative complications (OR=0.46; P<0.01), 98 vs 116 minutes for operative time (20.5% increase; P<0.001), 8.65 vs 8.45 days for postoperative stay (3.6% reduction; P=0.003), and $6103 vs $6062 for cost (1.7% reduction; P=0.018). CONCLUSION: B TURP had significantly lower rates of transfusion and postoperative complications, but a longer operative time. The impacts of B-TURP on shortening the hospital stay and lowering the costs were of little clinical significance. PMID- 22296568 TI - UK consensus guidelines for the use of the protease inhibitors boceprevir and telaprevir in genotype 1 chronic hepatitis C infected patients. AB - BACKGROUND: The nonstructural 3 serine protease inhibitors (PIs), boceprevir and telaprevir, represent the first in a new generation of directly acting antivirals against genotype 1 hepatitis C (HCV) infection. When used in combination with pegylated interferon and ribavirin, these drugs greatly improve sustained virological response rates in both treatment-naive patients and patients who have had previous virological failure on treatment. However, the addition of these new agents will increase the complexity of therapeutic regimens, the rates of side effects and costs. AIMS: To review concisely the current evidence and to suggest current best practice, for the use of telaprevir and boceprevir in the management of chronic genotype 1 HCV infection. METHODS: These guidelines for the use of boceprevir and telaprevir have been formulated following extensive review of the current literature, are based on the consensus opinion of a panel of national experts, and have been openly discussed and debated at a national meeting of HCV care providers. RESULTS: We have made recommendations on a number of the key practical issues facing HCV care providers: (i) Which patients to treat?; (ii) Standards for the provision of care; (iii) Pre-treatment considerations; (iv) Which treatment regimens to use?; (v) Stopping rules; and (vi) Management of adverse effects. Finally, we have produced suggested algorithms for the assessment and treatment of these patients. CONCLUSIONS: These UK Consensus guidelines indicate the current best practice for the use of boceprevir and telaprevir in the management of genotype 1 chronic HCV infection. PMID- 22296569 TI - Preparation of calcium alginate nanoparticles using water-in-oil (W/O) nanoemulsions. AB - A procedure for the preparation of calcium alginate nanoparticles in the aqueous phase of water-in-oil (W/O) nanoemulsions was developed. The emulsions were produced from mixtures of the nonionic surfactant tetraethylene glycol monododecyl ether (C(12)E(4)), decane, and aqueous solutions of up to 2 wt % sodium alginate by means of the phase inversion temperature (PIT) emulsification method. This method allows the preparation of finely dispersed emulsions without a large input of mechanical energy. With alginate concentrations of 1-2 wt % in the aqueous phase, emulsions showed good stability against Ostwald ripening and narrow, monomodal distributions of droplets with radii <100 nm. Gelation of the alginate was induced by the addition of aqueous CaCl(2) to the emulsions under stirring, and particles formed were collected using a simple procedure based on extraction of the surfactant on addition of excess oil. The final particles were characterized using cryo-transmission electron microscopy (cryo-TEM) and dynamic light scattering (DLS). They were found to be essentially spherical with a homogeneous interior, and their size was similar to that of the initial emulsion droplets. The herein presented "low-energy" method for preparation of biocompatible nanoparticles has the potential to be used in various applications, e.g., for the encapsulation of sensitive biomacromolecules. PMID- 22296570 TI - Preterm cognitive outcome and socioeconomic status. PMID- 22296571 TI - Enantioselective cyclizations of silyloxyenynes catalyzed by cationic metal phosphine complexes. AB - The discovery of complementary methods for enantioselective transition metal catalyzed cyclization with silyloxyenynes has been accomplished using chiral phosphine ligands. Under palladium catalysis, 1,6-silyloxyenynes bearing a terminal alkyne led to the desired five-membered ring with high enantioselectivities (up to 91% ee). As for reactions under cationic gold catalysis, 1,6- and 1,5-silyloxyenynes bearing an internal alkyne furnished the chiral cyclopentane derivatives with excellent enantiomeric excess (up to 94% ee). Modification of the substrate by incorporating an alpha,beta-unsaturation led to the discovery of a tandem cyclization. Remarkably, using silyloxy-1,3-dien 7-ynes under gold catalysis conditions provided the bicyclic derivatives with excellent diastereo- and enantioselectivities (up to >20:1 dr and 99% ee). PMID- 22296572 TI - Biomimetic poly(ethylene glycol)-based hydrogels as scaffolds for inducing endothelial adhesion and capillary-like network formation. AB - The extracellular matrix (ECM) is an attractive model for designing synthetic scaffolds with a desirable environment for tissue engineering. Here, we report on the synthesis of ECM-mimetic poly(ethylene glycol) (PEG) hydrogels for inducing endothelial cell (EC) adhesion and capillary-like network formation. A collagen type I-derived peptide GPQGIAGQ (GIA)-containing PEGDA (GIA-PEGDA) was synthesized with the collagenase-sensitive GIA sequence attached in the middle of the PEGDA chain, which was then copolymerized with RGD capped-PEG monoacrylate (RGD-PEGMA) to form biomimetic hydrogels. The hydrogels degraded in vitro with the rate dependent on the concentration of collagenase and also supported the adhesion of human umbilical vein ECs (HUVECs). Biomimetic RGD/GIA-PEGDA hydrogels with incorporation of 1% RGD-PEGDA into GIA-PEGDA hydrogels induced capillary like organization when HUVECs were seeded on the hydrogel surface, while RGD/PEGDA and GIA-PEGDA hydrogels did not. These results indicate that both cell adhesion and biodegradability of scaffolds play important roles in the formation of capillary-like networks. PMID- 22296573 TI - Quantitative microbial risk assessment of human illness from exposure to marine beach sand. AB - Currently no U.S. federal guideline is available for assessing risk of illness from sand at recreational sites. The objectives of this study were to compute a reference level guideline for pathogens in beach sand and to compare these reference levels with measurements from a beach impacted by nonpoint sources of contamination. Reference levels were computed using quantitative microbial risk assessment (QMRA) coupled with Monte Carlo simulations. In order to reach an equivalent level of risk of illness as set by the U.S. EPA for marine water exposure (1.9 * 10(-2)), levels would need to be at least about 10 oocysts/g (about 1 oocyst/g for a pica child) for Cryptosporidium, about 5 MPN/g (about 1 MPN/g for pica) for enterovirus, and less than 10(6) CFU/g for S. aureus. Pathogen levels measured in sand at a nonpoint source recreational beach were lower than the reference levels. More research is needed in evaluating risk from yeast and helminth exposures as well as in identifying acceptable levels of risk for skin infections associated with sand exposures. PMID- 22296574 TI - Model system for cell adhesion mediated by weak carbohydrate-carbohydrate interactions. AB - The multivalent carbohydrate-carbohydrate interaction between membrane-anchored epitopes derived from the marine sponge Microciona prolifera has been explored by colloidal probe microscopy. An in situ coupling of sulfated and non-sulfated disaccharides to membrane-coated surfaces was employed to mimic native cell-cell contacts.The dynamic strength of the homomeric self-association was measured as a function of calcium ions and loading rate. A deterministic model was used to estimate the basic energy landscape and number of participating bonds in the contact zone. PMID- 22296575 TI - Risk factors for patient-reported medical errors in eleven countries. AB - OBJECTIVES: The aim of this study was to identify common risk factors for patient reported medical errors across countries. In country-level analyses, differences in risks associated with error between health care systems were investigated. The joint effects of risks on error-reporting probability were modelled for hypothetical patients with different health care utilization patterns. DESIGN: Data from the Commonwealth Fund's 2010 lnternational Survey of the General Public's Views of their Health Care System's Performance in 11 Countries. SETTING: Representative population samples of 11 countries were surveyed (total sample = 19,738 adults). Utilization of health care, coordination of care problems and reported errors were assessed. Regression analyses were conducted to identify risk factors for patients' reports of medical, medication and laboratory errors across countries and in country-specific models. RESULTS: Error was reported by 11.2% of patients but with marked differences between countries (range: 5.4-17.0%). Poor coordination of care was reported by 27.3%. The risk of patient-reported error was determined mainly by health care utilization: Emergency care (OR = 1.7, P < 0.001), hospitalization (OR = 1.6, P < 0.001) and the number of providers involved (OR three doctors = 2.0, P < 0.001) are important predictors. Poor care coordination is the single most important risk factor for reporting error (OR = 3.9, P < 0.001). Country-specific models yielded common and country-specific predictors for self-reported error. For high utilizers of care, the probability that errors are reported rises up to P = 0.68. CONCLUSIONS: Safety remains a global challenge affecting many patients throughout the world. Large variability exists in the frequency of patient-reported error across countries. To learn from others' errors is not only essential within countries but may also prove a promising strategy internationally. PMID- 22296576 TI - Wound outcomes in patients with advanced illness. AB - A prospective case series was studied to assess the potential for complete healing of wounds among patients with advanced illness referred to a regional palliative care program in Toronto, Canada. Two hundred and eighty-two patients, of which 148 were primarily diagnosed with cancer and 134 with non cancer advanced illness, were assessed and followed until their deaths. On the baseline initial referral date, 823 wounds were documented. The wound classes assessed included pressure ulcers, malignant wounds, skin tears, venous leg ulcers, diabetic foot ulcers and arterial leg/foot ulcers. Proportions of patients showing complete healing of at least one wound were calculated, stratified by patient's survival time post-baseline (1 week, 1 month, 3 months and 6 months). Proportions of patients showing complete healing of at least one wound increased the longer patients lived and ranged between 12.9% and 43.5% for stage I pressure ulcers, 0% and 60% for stage II pressure ulcers, 2.4% and 100% for skin tears, 10% and 100% for venous leg ulcers and 0% and 50% for diabetic foot ulcers. Only one person showed complete healing of a stage III pressure ulcer and no complete healing was observed with stage IV pressure ulcers, unstageable pressure ulcers, malignant wounds and arterial leg/foot ulcers. PMID- 22296577 TI - Right ventricular mass in an asymptomatic HIV positive patient. AB - Human immunodeficiency virus (HIV)- positive patients are known to have a higher risk of cardiovascular complications that are related to the underlying infection itself and also to the complications of their medical treatment. As longevity of these patients has increased owing to the advances in antiretroviral therapies, cardiovascular diseases including coagulative disorders may be more commonly encountered. A case of a right ventricular mass in an asymptomatic HIV positive patient detected by echocardiography is presented and the surgical management is described. PMID- 22296580 TI - Gut region-specific diabetic damage to the capillary endothelium adjacent to the myenteric plexus. AB - OBJECTIVE: Damage in the capillaries supplying the MP has been proposed as a critical factor in the development of diabetic enteric neuropathy. We therefore investigated connections between STZ-induced diabetes and the BM morphology, the size of caveolar compartments, the width of TJs, the transport of albumin, and the quantitative features of Cav-1 and eNOS expression in these microvessels. METHODS: Gut segments from diabetic rats were compared with those from insulin treated diabetics and those from controls. The effects of diabetes on the BM, the caveolar compartments, and the TJs were evaluated morphometrically. The quantitative features of the albumin transport were investigated by postembedding immunohistochemistry. The diabetes-related changes in Cav-1 and eNOS expression were assessed by postembedding immunohistochemistry and molecular method. RESULTS: Thickening of the BM, enlargement of the caveolar compartments, opening of the junctions, enhanced transport of albumin, and overexpression of Cav-1 and eNOS were documented in diabetic animals. Insulin replacement in certain gut segments prevented the development of these alterations. CONCLUSIONS: These data provide morphological, functional, and molecular evidence that the endothelial cells in capillaries adjacent to the MP is a target of diabetic damage in a regional manner. PMID- 22296581 TI - A network of enzymes involved in repair of oxidative DNA damage in Neisseria meningitidis. AB - Although oxidative stress is a key aspect of innate immunity, little is known about how host-restricted pathogens successfully repair DNA damage. Base excision repair is responsible for correcting nucleobases damaged by oxidative stress, and is essential for bloodstream infection caused by the human pathogen, Neisseria meningitidis. We have characterized meningococcal base excision repair enzymes involved in the recognition and removal of damaged nucleobases, and incision of the DNA backbone. We demonstrate that the bi-functional glycosylase/lyases Nth and MutM share several overlapping activities and functional redundancy. However, MutM and other members of the GO system, which deal with 8-oxoG, a common lesion of oxidative damage, are not required for survival of N. meningitidis under oxidative stress. Instead, the mismatch repair pathway provides back-up for the GO system, while the lyase activity of Nth can substitute for the meningococcal AP endonuclease, NApe. Our genetic and biochemical evidence shows that DNA repair is achieved through a robust network of enzymes that provides a flexible system of DNA repair. This network is likely to reflect successful adaptation to the human nasopharynx, and might provide a paradigm for DNA repair in other prokaryotes. PMID- 22296582 TI - Statistical analysis of agronomical factors and weather conditions influencing deoxynivalenol levels in oats in Scandinavia. AB - The relationship between weather data and agronomical factors and deoxynivalenol (DON) levels in oats was examined with the aim of developing a predictive model. Data were collected from a total of 674 fields during periods of up to 10 years in Finland, Norway and Sweden, and included DON levels in the harvested oats crop, agronomical factors and weather data. The results show that there was a large regional variation in DON levels, with higher levels in one region in Norway compared with other regions in Norway, Finland and Sweden. In this region the median DON level was 1000 ng g-1 and the regulatory limit for human consumption (1750 ng g-1) was exceeded in 28% of the samples. In other regions the median DON levels ranged from 75 to 270 ng g-1, and DON levels exceeded 1750 ng g-1 in 3-8% of the samples. Including more variables than region in a multiple regression model only increased the adjusted coefficient of determination from 0.17 to 0.24, indicating that very little of the variation in DON levels could be explained by weather data or agronomical factors. Thus, it was not possible to predict DON levels based on the variables included in this study. Further studies are needed to solve this problem. Apparently the infection and/or growth of DON producing Fusarium species are promoted in certain regions. One possibility may be to study the species distribution of fungal communities and their changes during the oats cultivation period in more detail. PMID- 22296583 TI - Editorial comment for Cost et al. PMID- 22296584 TI - Adjunctive GnRH-a treatment attenuates depletion of ovarian reserve associated with cyclophosphamide therapy in premenopausal SLE patients. AB - BACKGROUND: We measured antimullerian hormone (AMH), a marker of ovarian reserve, in women with lupus treated with cyclophosphamide (CYC) (group I), CYC plus gonadotropin-releasing hormone agonist (GnRH-a) (group II) or neither (group III). We hypothesized that AMH would be diminished in women exposed to CYC versus women receiving adjunctive GnRH-a treatment or no CYC exposure. METHODS: Forty eight premenopausal lupus patients were retrospectively divided into three treatment groups: CYC alone (group I, n = 11), CYC + GnRH-a (group II, n = 10) and neither (group III, n = 27). Serum AMH levels between groups were compared using a nonparametric test (Wilcoxon rank-sum). Multiple linear regression adjusting for age was performed. RESULTS: AMH (ng/mL) levels at the last collection were significantly lower in group I versus group III (mean +/- SD: 0.18 +/- 0.20 group I vs 1.33 +/- 1.59 group III; p = 0.015), and versus group II (mean +/- SD: 0.86 +/- 1.06; p = 0.018). When centered on age 30 years, average AMH levels for group I, group II and group III were 0.20, 0.44 and 1.00, respectively. When adjusted for age, AMH between all groups was significantly different (p<0.0001). CONCLUSION: Posttreatment AMH levels were significantly higher among patients receiving CYC + GnRH-a compared to CYC alone, suggesting that GnRH-a coadministration mitigates CYC-induced ovarian injury. PMID- 22296585 TI - The use of ADAMTS13 activity, platelet count, and serum creatinine to differentiate acquired thrombotic thrombocytopenic purpura from other thrombotic microangiopathies. PMID- 22296586 TI - Evaluation of diethyl-3-3'-(9,10-anthracenediyl)bis acrylate as a probe for singlet oxygen formation during photodynamic therapy. AB - The cell-permeable anthracene analog diethyl-3-3'-(9,10-anthracenediyl)bis acrylate (DADB) was recently identified as a highly selective probe for singlet oxygen ((1)O(2)). Now, we show that DADB can be used to monitor (1)O(2) formation in cell culture during photodynamic therapy. An atypical property of DADB is that fluorescence emission is decreased upon oxidation. Using photosensitizers that target specific organelles, we determined that DADB could detect (1)O(2) whether formed in ER, mitochondria or lysosomes. DADB fluorescence was not, however, significantly altered when the photosensitizing agent was the palladium bacteriopheophorbide termed WST11, an agent reported to produce mainly oxygen radicals upon irradiation in an aqueous environment, whereas singlet oxygen was formed in organic solvents. PMID- 22296587 TI - Reagents for astatination of biomolecules. 6. An intact antibody conjugated with a maleimido-closo-decaborate(2-) reagent via sulfhydryl groups had considerably higher kidney concentrations than the same antibody conjugated with an isothiocyanato-closo-decaborate(2-) reagent via lysine amines. AB - We are investigating the use of an (211)At-labeled anti-CD45 monoclonal antibody (mAb) as a replacement of total body irradiation in conditioning regimens designed to decrease the toxicity of hematopoietic cell transplantation (HCT). As part of that investigation, dose-escalation studies were conducted in dogs using (211)At-labeled anticanine CD45 mAb, CA12.10C12, conjugated with a maleimido closo-decaborate(2-) derivative, 4. Unacceptable renal toxicity was noted in the dogs receiving doses in the 0.27-0.62 mCi/kg range. This result was not anticipated, as no toxicity had been noted in prior biodistribution and toxicity studies conducted in mice. Studies were conducted to understand the cause of the renal toxicity and to find a way to circumvent it. A dog biodistribution study was conducted with (123)I-labeled CA12.10C12 that had been conjugated with 4. The biodistribution data showed that 10-fold higher kidney concentrations were obtained with the maleimido-conjugate than had been obtained in a previous biodistribution study with (123)I-labeled CA12.10C12 conjugated with an amine reactive phenylisothiocyanato-CHX-A" derivative. The difference in kidney concentrations observed in dogs for the two conjugation approaches led to an investigation of the reagents. SE-HPLC analyses showed that the purity of the CA12.10C12 conjugated via reduced disulfides was lower than that obtained with amine-reactive conjugation reagents, and nonreducing SDS-PAGE analyses indicated protein fragments were present in the disulfide reduced conjugate. Although we had previously prepared closo-decaborate(2-) derivatives with amine-reactive functional groups (e.g., 6 and 8), a new, easily synthesized, amine-reactive (phenylisothiocyanate) derivative, 10, was prepared for use in the current studies. A biodistribution was conducted with coadministered (125)I- and (211)At labeled CA12.10C10 conjugated with 10. In that study, lower kidney concentrations were obtained for both radionuclides than had been obtained in the earlier study of the same antibody conjugated with 4 after reduction of disulfide bonds. PMID- 22296588 TI - The utility of Gram stains and culture in the management of limb ulcers in persons with diabetes. AB - In Tanzania, limited laboratory services often preclude routine identification of microorganisms that cause infections in persons with diabetes. Thus, we carried out this study to determine the utility of a Gram stain alone versus culture in guiding appropriate antimicrobial therapy. During February 2006 to December 2007 (study period), deep tissue biopsies were obtained from persons with diabetes presenting to the Muhimbili National Hospital (MNH) with infected limb ulcers. Specimens were Gram-stained then cultured for bacteria and fungi. Biopsies were obtained from 128 patients. Of 128 cultures, 118 (92%) yielded bacterial or fungal growth; 59 (50%) of these 118 cultures yielded mixed growth (80% included Gram-negative organisms); 38 (32%) and 20 (17%) yielded Gram-negative and Gram positive organisms alone, respectively. The predictive value positive of a Gram stain for bacterial growth was 93% (110/118); a Gram-positive stain was 75% (15/20) predictive of growth of Gram-positive organisms whereas a Gram-negative stain was 82% (31/38) predictive of growth of Gram-negative organisms. In regions with limited resources, a Gram stain of an ulcer biopsy that is carefully procured is largely predictive of the type of microorganism causing infection. Gram staining of deep tissue biopsies might have a potential role to play in the management of infected diabetic limb ulcers. PMID- 22296589 TI - Reexamination of the ethics of placebo use in clinical practice. AB - A placebo is a substance or intervention believed to be inactive, but is administered by the healthcare professional as if it was an active medication. Unlike standard treatments, clinical use of placebo usually involves deception and is therefore ethically problematic. Our attitudes toward the clinical use of placebo, which inevitably includes deception or withholding information, have a tremendous effect on our practice regarding truth-telling and informed consent. A casual attitude towards it weakens the current practice based on shared decision making and mutual trust between patients and healthcare professionals. Issues concerning the clinical use of placebo are thus intimately related to patient provider relationships, the public's trust in medicine, and medical education. A review of recent survey studies suggests that the clinical use of placebo appears to be fairly well accepted among healthcare professionals and is common in clinical settings in various countries. However, we think that an ethical discussion is urgently needed because of its controversial nature. If judged to be ethically wrong, the practice should end. In the present paper, we discuss the ethicality of the clinical use of placebo with deception and argue against it, concluding that it is unethical and should be banned. We will show that most arguments in favor of the clinical use of placebo can be refuted and are therefore incorrect or weak. These arguments will be presented and examined individually. Finally, we will briefly consider issues relevant to the clinical use of placebo without deception. PMID- 22296590 TI - Religious practices, beliefs, and mental health: variations across ethnicity. AB - OBJECTIVES: We examined whether Black Americans and Hispanic Americans experienced greater mental health benefits from religious involvement than White Americans, and whether these benefits would be mediated through three psychosocial factors--social support, meaning, and forgiveness. METHODS: Utilizing data from a probability sample of Chicago-based adults (n=3103), ethnicity-stratified multivariate regression models estimated the association of religiosity with depressive symptoms, anxiety symptoms, and major depressive disorder (MDD). Models controlled for potential confounders and psychosocial mediators. RESULTS: Contrary to our hypotheses, religiously involved Black Americans and Hispanic Americans did not experience greater mental health benefits than their White counterparts. For White Americans alone, service attendance was inversely related to depressive symptoms, anxiety symptoms, and MDD. Religious saliency was consistently associated with worse mental health for Hispanic Americans only. However, both meaning and forgiveness conferred mental health benefits for all three groups. CONCLUSIONS: The benefits of specific aspects of religious involvement vary across ethnicity. Caution is necessary in any effort to bring religion into the health domain. Our findings, if replicated, suggest that initiatives that facilitate a sense of purpose or forgiveness are likely to prove promising in improving mental health, regardless of race or ethnicity. PMID- 22296591 TI - Self-esteem among German nurses: does academic education make a difference? AB - Self-esteem is not typically associated with the nursing profession. However, the concept is indispensible for job satisfaction and good-quality patient care. Many healthcare systems are confronted with declining numbers of qualified nurses, and desperately seek suitable strategies to recruit and retain sufficient trainees and junior staff. This investigation examined self-esteem in 212 German nurses using the Rosenberg Self-Esteem Scale. Nurses with an academic degree displayed a statistically significant higher level of self-esteem than nurses without academic education (P < 0.01). The type of professional training may therefore have a direct effect on the self-esteem, thus offering a myriad of potential benefits to both nurses and patients. Self-esteem is a quality relevant to this profession and, as such, the findings of research in this area should be reflected in the design of nurse training curricula. PMID- 22296592 TI - Commentary on "Are natural orifice transluminal endoscopic surgery and single incision surgery viable techniques for cholecystectomy?". PMID- 22296593 TI - Saddle coronary thrombus after aortic valve replacement. PMID- 22296594 TI - Delivery of dermatan sulfate from polyelectrolyte complex-containing alginate composite microspheres for tissue regeneration. AB - Dermatan sulfate (DS) is a glycosaminoglycan (GAG) with a great potential as a new therapeutic agent in tissue engineering. The aim of the present study was to investigate the formation of polyelectrolyte complexes (PECs) between chitosan and dermatan sulfate (CS/DS) and delivery of DS from PEC-containing alginate/chitosan/dermatan sulfate (Alg/CS/DS) microspheres for application in tissue regeneration. The CS/DS complexes were initially formed at different conditions including varying CS/DS ratio (positive/negative charge ratio), buffer, and pH. The obtained CS/DS complexes exhibited stronger electrostatic interaction, smaller complex size, and more stable colloidal structure when chitosan was in large excess (CS/DS 3:1) and prepared at pH 3.5 as compared to pH 5 using acetate buffer. The CS/DS complexes were subsequently incorporated into an alginate matrix by spray drying to form Alg/CS/DS composite microspheres with a DS encapsulation efficiency of 90-95%. The excessive CS induced a higher level of sustained DS release into Tris buffer (pH 7.4) from the microspheres formulated at pH 3.5; however, the amount of CS did not have a significant effect on the release from the microspheres formulated at pH 5. Significant cell proliferation was stimulated by the DS released from the microspheres in vitro. The present results provide a promising drug delivery strategy using PECs for sustained release of DS from microspheres intended for site-specific drug delivery and ultimately for use in tissue engineering. PMID- 22296595 TI - Occurrences and fates of hydroxylated polybrominated diphenyl ethers in marine sediments in relation to trophodynamics. AB - While occurrences and origins of hydroxylated (OH-) polybrominated diphenyl ethers (PBDEs) in organisms have been reported, the fates of these compounds in abiotic matrixes and related trophodynamics are unclear. The present study measured concentrations of nine OH-PBDEs, twelve methoxylated (MeO-) PBDEs, and eleven PBDEs in marine sediments and explored the trophodynamics of OH-PBDEs in five invertebrates, eight fish, and two species of birds from Liaodong Bay, north China. While concentrations of PBDEs were less than the limit of quantification in sediments, concentrations of SigmaOH-PBDEs and SigmaMeO-PBDEs were 3.2-116 pg/g dry weight (dw) and 3.8-56 pg/g dw, respectively. When the detected compounds were incubated in native marine sediments the interconversion between 6 OH-BDE47 and 6-MeO-BDE47 was observed. This result is consistent with the similar spatial distributions and significant correlation between the concentrations of these naturally occurring compounds. 6-OH-BDE47 and 2'-OH-BDE68 were detected as the two major congeners in organisms collected from Liaodong Bay, and concentrations were 0.24 +/- 0.005 ng/g lw (lipid weight) and 0.088 +/- 0.006 ng/g lw, respectively. Biota-sediment accumulation factors (BSAFs) for invertebrates of 6-OH-BDE47 and 2'-OH-BDE68 were 0.017-0.96 and 0.19-1.5 (except for short-necked clam: 6.3), respectively. Lipid-normalized concentrations of 6 OH-BDE47 and 2'-OH-BDE68 decreased significantly with trophic level with TMFs of 0.21 and 0.15, respectively. The fates of OH-PBDEs in sediment together with their trophodynamics in marine food webs suggested that OH-PBDEs are partitioned into sediment and undergo biodilution in the marine food web. PMID- 22296596 TI - Physico-chemical control over the single- or double-wall structure of aluminogermanate imogolite-like nanotubes. AB - It is known that silicon can be successfully replaced by germanium atoms in the synthesis of imogolite nanotubes, leading to shorter and larger AlGe nanotubes. Beside the change in morphology, two characteristics of the AlGe nanotube synthesis were recently discovered. AlGe imogolite nanotubes can be synthesized at much higher concentrations than AlSi imogolite. AlGe imogolite exists in the form of both single-walled (SW) and double-walled (DW) nanotubes, whereas DW AlSi imogolites have never been observed. In this article, we give details on the physicochemical control over the SW or DW AlGe imogolite structure. For some conditions, an almost 100% yield of SW or DW nanotubes is demonstrated. We propose a model for the formation of SW or DW AlGe imogolite, which also explains why DW AlSi imogolites or higher wall numbers for AlGe imogolite are not likely to be formed. PMID- 22296598 TI - Activation of c-Jun N-terminal kinase in non-cancerous liver tissue predicts a high risk of recurrence after hepatic resection for hepatocellular carcinoma. AB - AIM: Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer deaths worldwide. Hepatic resection is the mainstay of curative treatment for early stage HCC. Although c-Jun N-terminal kinase (JNK) activation contributes to hepatocyte proliferation and HCC development in mice, the extent of involvement of JNK in human HCC development is unknown. The aim of this study is to assess the predictive value of JNK for postoperative recurrence in HCC. METHODS: From April 2005 to March 2008, 159 patients underwent curative resection for HCC. From the 159 patients, 20 patients each matched for age, gender and etiology were registered as three groups: (i) without recurrence (no recurrence group), (ii) with recurrence within one year after surgery (early recurrence group), and (iii) with recurrence at one year or more after surgery (late recurrence group) (a cross-sectional control study). We investigated factors contributing to postoperative early and late phase recurrence. RESULTS: Multivariate analysis using a Logistic regression model showed that JNK activity in non-cancerous liver tissue was correlated with postoperative late recurrence. (P = 0.02, odds ratio; 5.79, 95% confidence interval [CI]; 1.33-25.36). CONCLUSIONS: JNK activity in non-cancerous liver tissue is considered as a reliable predictive biomarker for post-operative recurrence in HCC. PMID- 22296597 TI - RECQL4 localizes to mitochondria and preserves mitochondrial DNA integrity. AB - RECQL4 is associated with Rothmund-Thomson Syndrome (RTS), a rare autosomal recessive disorder characterized by premature aging, genomic instability, and cancer predisposition. RECQL4 is a member of the RecQ helicase family, and has many similarities to WRN protein, which is also implicated in premature aging. There is no information about whether any of the RecQ helicases play roles in mitochondrial biogenesis, which is strongly implicated in the aging process. Here, we used microscopy to visualize RECQL4 in mitochondria. Fractionation of human and mouse cells also showed that RECQL4 was present in mitochondria. Q-PCR amplification of mitochondrial DNA demonstrated that mtDNA damage accumulated in RECQL4-deficient cells. Microarray analysis suggested that mitochondrial bioenergetic pathways might be affected in RTS. Measurements of mitochondrial bioenergetics showed a reduction in the mitochondrial reserve capacity after lentiviral knockdown of RECQL4 in two different primary cell lines. Additionally, biochemical assays with RECQL4, mitochondrial transcription factor A, and mitochondrial DNA polymerase gamma showed that the polymerase inhibited RECQL4's helicase activity. RECQL4 is the first 3'-5' RecQ helicase to be found in both human and mouse mitochondria, and the loss of RECQL4 alters mitochondrial integrity. PMID- 22296599 TI - Cavernous hemangioma of the right atrium. PMID- 22296600 TI - Effect of substrate availability on nitrous oxide production by deammonification processes under anoxic conditions. AB - Due to its high global warming potential, nitrous oxide (N(2)O) emissions from wastewater treatment processes have recently received a high degree of attention. Nevertheless, there is still a lack of information regarding the microbiological processes leading to N(2)O production. In this study, two lab-scale sequencing batch reactors were operated with deammonification biomass to investigate the role of denitrification and the influence of substrate availability regarding N(2)O formation during the anoxic phase of deammonification. Three different operational phases were established: within the first phase conversion by anammox was favoured and after a transition phase, denitrification activity was promoted. Low nitrous oxide production was observed during stable operation aiming for anammox conversion. Pulsed inflow of the wastewater containing ammonium (NH(4)(+)) and nitrite (NO(2)(-)) led to increased N(2)O production rates. Within the period of denitrification as dominating nitrogen conversion process, the nitrous oxide concentration level was higher during continuous inflow conditions, but the reaction to pulsed inflow was less pronounced. The results indicated that denitrification was responsible for N(2)O formation from the deammonification biomass. Operational settings to achieve suppression of denitrification processes to a large extend were deducted from the results of the experiments. PMID- 22296601 TI - Structure-based design of potent and ligand-efficient inhibitors of CTX-M class A beta-lactamase. AB - The emergence of CTX-M class A extended-spectrum beta-lactamases poses a serious health threat to the public. We have applied structure-based design to improve the potency of a novel noncovalent tetrazole-containing CTX-M inhibitor (K(i) = 21 MUM) more than 200-fold via structural modifications targeting two binding hot spots, a hydrophobic shelf formed by Pro167 and a polar site anchored by Asp240. Functional groups contacting each binding hot spot independently in initial designs were later combined to produce analogues with submicromolar potencies, including 6-trifluoromethyl-3H-benzoimidazole-4-carboxylic acid [3-(1H-tetrazol-5 yl)-phenyl]-amide, which had a K(i) value of 89 nM and reduced the MIC of cefotaxime by 64-fold in CTX-M-9 expressing Escherichia coli . The in vitro potency gains were accompanied by improvements in ligand efficiency (from 0.30 to 0.39) and LipE (from 1.37 to 3.86). These new analogues represent the first nM affinity noncovalent inhibitors of a class A beta-lactamase. Their complex crystal structures provide valuable information about ligand binding for future inhibitor design. PMID- 22296602 TI - Linkage isomerism in coordination polymers. AB - The use of the recently prepared polynitrile ligand tcnopr3OH(-) ([(NC)(2)CC(OCH(2)CH(2)CH(2)OH)C(CN)(2)](-)) with different salts of Fe(II), Co(II), and Ni(II) has led to a very rare example of linkage isomerism in a coordination chain. These pairs of linkage isomers can be formulated as [M(tcnopr3OH-kappaN,kappaO)(2)(H(2)O)(2)]; M = Fe (1), Co (3), and Ni(5) and [M(tcnopr3OH-kappaN,kappaN')(2)(H(2)O)(2)]; M = Fe (2), Co (4), and Ni (6). Compounds 1-2, 3-4, and 5-6 are three pairs of linkage isomers since they present the same formula and chain structure and they only differ in the connectivity of the polynitrile ligand bridging the metal ions in the chain: through a N and an O atom (1kappaN:2kappaO-isomer) or through two N atoms (1kappaN:2kappaN'-isomer). The magnetic properties show, as expected, very similar behaviors for both isomers. PMID- 22296603 TI - Nickel-catalyzed enantioselective cross-couplings of racemic secondary electrophiles that bear an oxygen leaving group. AB - To date, effective nickel-catalyzed enantioselective cross-couplings of alkyl electrophiles that bear oxygen leaving groups have been limited to reactions of allylic alcohol derivatives with Grignard reagents. In this Communication, we establish that, in the presence of a nickel/pybox catalyst, a variety of racemic propargylic carbonates are suitable partners for asymmetric couplings with organozinc reagents. The method is compatible with an array of functional groups and utilizes commercially available catalyst components. The development of a versatile nickel-catalyzed enantioselective cross-coupling process for electrophiles that bear a leaving group other than a halide adds a significant new dimension to the scope of these reactions. PMID- 22296604 TI - Control system design for a Continuous Positive Airway Pressure ventilator. AB - Continuous Positive Airway Pressure (CPAP) ventilation remains a mainstay treatment for obstructive sleep apnea syndrome (OSAS). Good pressure stability and pressure reduction during exhalation are of major importance to ensure clinical efficacy and comfort of CPAP therapy. In this study an experimental CPAP ventilator was constructed using an application-specific CPAP blower/motor assembly and a microprocessor. To minimize pressure variations caused by spontaneous breathing as well as the uncomfortable feeling of exhaling against positive pressure, we developed a composite control approach including the feed forward compensator and feedback proportional-integral-derivative (PID) compensator to regulate the pressure delivered to OSAS patients. The Ziegler and Nichols method was used to tune PID controller parameters. And then we used a gas flow analyzer (VT PLUS HF) to test pressure curves, flow curves and pressure volume loops for the proposed CPAP ventilator. The results showed that it met technical criteria for sleep apnea breathing therapy equipment. Finally, the study made a quantitative comparison of pressure stability between the experimental CPAP ventilator and commercially available CPAP devices. PMID- 22296605 TI - The hour lecture that changed sexual medicine--the Giles Brindley injection story. PMID- 22296607 TI - Female sexual function during pregnancy and postpartum. PMID- 22296608 TI - The combined GnRH-agonist and intrauterine levonorgestrel-releasing system treatment of complicated atypical hyperplasia and endometrial cancer: a pilot study. AB - In this article, we present the results of organ-preserving treatment applied in 24 patients of reproductive age with atypical endometrial hyperplasia or early stage endometrial cancer. All of them would like to preserve their reproductive potential. Thirteen women with atypical endometrial hyperplasia were treated with the combination of six intramuscular injections of 3.75 mg gonadotropin-releasing hormone agonist (GnRHa)--leuproreline acetate depot every 4 weeks. After the third injection of 3.75 mg of leuproreline acetate, the levonorgestrel intrauterine hormonal system containing 52 mg levonorgestrel (Mirena(r), Bayer, Germany) was inserted for at least 6 months. In 11 women with stage IA well differentiated endometrial adenocarcinoma, hormonal therapy included nine intramuscular injections of 3.75 mg of GnRHa every 4 weeks. After the third injection of 3.75 mg of GnRHa, we also inserted a GnRH-IUS (Mirena(r)) for at least 12 months. This type of therapy was effective for all these patients and may be offered to be used as an alternative to surgery in women with atypical endometrial hyperplasia or early stage 1A well-differentiated endometrial cancer in women of reproductive age. Three women with endometrial cancer became pregnant and two of them delivered at term and one has an ongoing pregnancy. PMID- 22296609 TI - Alogliptin benzoate for the treatment of type 2 diabetes. AB - INTRODUCTION: Alogliptin is a highly selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4). It is one of several agents of this class now available for treatment of type 2 diabetes. AREAS COVERED: This review is based upon a PubMed search and personal experience with alogliptin. The pharmacokinetics and pharmacodynamics of alogliptin are reviewed. The glucose-lowering effect of this agent is discussed as monotherapy and in combination with metformin, sulfonylurea, piogilitazone and insulin. The potential adverse effects of alogliptin are summarized. Alogliptin is compared with the other available DPP-4 inhibitors. EXPERT OPINION: Alogliptin is an additional choice in the group of DPP-4 inhibitors. As a group, these agents have a relatively modest glucose lowering effect, inferior to that of metformin, sulfonylureas, and insulin. They do not have the benefit of weight loss offered by the glucagon-like polypeptide (GLP)-1 agonists. The primary use of DPP-4 inhibitors is in combination with other hypoglycemic agents, mainly metformin. Their principal advantage is a low incidence of hypoglycemia, making these agents desirable in patients such as the elderly and those with cardiac disease. A greater use of alogliptin and other DPP 4 inhibitors will occur if long-term studies show reduced cardiac events or long term retention of insulin secretory capacity. The Examine Trial, a large study of alogliptin in coronary disease patients, is now underway and could provide important supportive data. PMID- 22296610 TI - Cost-effectiveness analysis for clinicians. AB - In a climate of economic uncertainty, cost effectiveness analysis is a potentially important tool for making choices about health care interventions. Methods for such analyses are well established, but the results need to be interpreted carefully and are subject to bias. Making decisions based on results of cost-effectiveness analyses can involve setting thresholds, but for individual patients, there needs to be disaggregation of benefits and harms included in a quality adjusted life year to ensure appropriate consideration of benefits and harms as well as personal preferences and circumstances. PMID- 22296611 TI - Moral fiction or moral fact? The distinction between doing and allowing in medical ethics. AB - Opponents of physician-assisted suicide (PAS) maintain that physician withdrawal of-life-sustaining-treatment cannot be morally equated to voluntary active euthanasia. PAS opponents generally distinguish these two kinds of act by positing a possible moral distinction between killing and allowing-to-die, ceteris paribus. While that distinction continues to be widely accepted in the public discourse, it has been more controversial among philosophers. Some ethicist PAS advocates are so certain that the distinction is invalid that they describe PAS opponents who hold to the distinction as in the grip of 'moral fictions'. The author contends that such a diagnosis is too hasty. The possibility of a moral distinction between active euthanasia and allowing-to-die has not been closed off by the argumentative strategies employed by these PAS advocates, including the contrasting cases strategy and the assimilation of doing and allowing to a common sense notion of causation. The philosophical debate over the doing/allowing distinction remains inconclusive, but physicians and others who rely upon that distinction in thinking about the ethics of end-of-life care need not give up on it in response to these arguments. PMID- 22296612 TI - Inter-rater agreement in the assessment of abnormal chest X-ray findings for tuberculosis between two Asian countries. AB - BACKGROUND: Inter-rater agreement in the interpretation of chest X-ray (CXR) films is crucial for clinical and epidemiological studies of tuberculosis. We compared the readings of CXR films used for a survey of tuberculosis between raters from two Asian countries. METHODS: Of the 11,624 people enrolled in a prevalence survey in Hanoi, Viet Nam, in 2003, we studied 258 individuals whose CXR films did not exclude the possibility of active tuberculosis. Follow-up films obtained from accessible individuals in 2006 were also analyzed. Two Japanese and two Vietnamese raters read the CXR films based on a coding system proposed by Den Boon et al. and another system newly developed in this study. Inter-rater agreement was evaluated by kappa statistics. Marginal homogeneity was evaluated by the generalized estimating equation (GEE). RESULTS: CXR findings suspected of tuberculosis differed between the four raters. The frequencies of infiltrates and fibrosis/scarring detected on the films significantly differed between the raters from the two countries (P < 0.0001 and P = 0.0082, respectively, by GEE). The definition of findings such as primary cavity, used in the coding systems also affected the degree of agreement. CONCLUSIONS: CXR findings were inconsistent between the raters with different backgrounds. High inter-rater agreement is a component necessary for an optimal CXR coding system, particularly in international studies. An analysis of reading results and a thorough discussion to achieve a consensus would be necessary to achieve further consistency and high quality of reading. PMID- 22296613 TI - Eating disorders in medical students of Karachi, Pakistan-a cross-sectional study. AB - BACKGROUND: To assess the incidence of high-risk population of medical students with eating disorders in Karachi by using validated self-administered questionnaires. The earlier these disorders are diagnosed and assessed, the better the chances are for enhanced treatment and fuller recovery. Therefore, we intended to undertake a study to find out the frequency of such disorders among medical students of Karachi and design strategies to overcome them. FINDINGS: A descriptive cross sectional study was conducted in 435 medical students of Karachi. Data was collected using 2 self administered questionnaires, the SCOFF Eating Disorders Questionnaire and the Eating Attitudes Test (EAT-26). Subjects' body mass indexes (BMI) were also calculated. The data was sorted and analyzed in SPSS version 16. According to EAT-26, 22.75% individuals were found to be at high risk of eating disorders, with 87.9% females and 12.1% males. However, according to SCOFF questionnaire, 17% individuals were found to be at high-risk, with 78.4% females and 21.6% males. According to BMI calculation, 9% were severely underweight, 41.4% underweight, 41.1% normal, 7.6% overweight and 0.9% belonged to obese class 1. CONCLUSIONS: A significant fraction of medical students in Karachi are at high risk of development of eating disorders, females being more prone than males. Strategies should be designed to prevent occurrence of such disorders among medical students that would undoubtedly hamper the availability of dependable medical services in future. PMID- 22296614 TI - The conflict of safety versus access to new therapies: the FDA, clinical trial design, and neuromodulation. PMID- 22296615 TI - Neurotech report. PMID- 22296616 TI - The prospective evaluation of safety and success of a new method of introducing percutaneous paddle leads and complex arrays with an epidural access system. AB - OBJECTIVES: Spinal cord stimulation (SCS) has become a mainstay in the continuum of care for patients suffering from chronic neuropathic pain of the trunk and limbs. Options for placing these devices have included a percutaneous method of using an epidural needle to place a cylindrical (percutaneous) lead to stimulate the spinal cord, or an open laminotomy method for placing a paddle lead at the location of the surgical decompression of the laminae. Both of these methods have been successful in a high percentage of patients, but neither have been ideal. Limitations of the percutaneous leads have been inefficiency of power delivery, inability to achieve desired depth of stimulation in the spinal cord, occasional lead migration and difficulty covering complex pain patterns. Limitations of the paddle lead have been the need for surgical laminotomy, inability to steer the lead once placed, limits on placement in the vicinity of the surgical decompression, and a perceived risk of increased bleeding and trauma to the tissue. These factors have led many minimally invasive spine specialists to seek new options for SCS. This paper presents the initial US experience with a newly approved device to place both paddle leads, and multi-lead arrays into the epidural space via a percutaneous Seldinger-guided approach through a single needle placement. We will both describe the technique and review the outcomes of some of the early cases. MATERIALS AND METHODS: After Investigational Review Board clearance, patients consented to data collection in a prospective fashion regarding the use of a new percutaneous epidural introducer (Epiducer, St. Jude Neurological, Minneapolis, MN, USA) to place paddle leads and complex lead arrays. The patients underwent education regarding expectations and risks of the procedure consistent with our normal preoperative period. Patients underwent preoperative anesthesia screening and proper testing as outlined by the Joint Commission on Hospital Accreditation, and were given the opportunity to ask questions concerning the procedure. Once the patient wished to move forward, they were consented using the approved case reporting form and followed during the course of their care. The initial cases were performed in West Virginia with subsequent cases following at the other centers involved in this analysis. The outcomes of this analysis focused on three areas: 1. The technical success in placing the percutaneous sheath. This included the ability to successfully complete: * epidural access with a 14-gauge Tuohy needle * ability to place a styleted guidewire * ability to introduce the introduction system over the wire into the epidural space * ability to remove the guidewire and introduction tip leaving the 10-gauge sheath intact. 2. The ability to place the desired lead or leads into the epidural space via the percutaneous introduction sheath. 3. The presence of any major adverse event which were defined as: * nerve injury * paraplegia * worsening of baseline pain * epidural hematoma * epidural infection * dural tear * dural rent * retained device that could not be removed. This information was carefully recorded for each implant, and summarized in this communication. RESULTS: During the initial 30 days of the evaluation period, 43 epidural introduction systems were attempted in 38 patients. In patients in whom more than one paddle lead was placed, the system required the reinsertion of the guidewire through the Epiducer, removal of the Epiducer, and rewiring over the guidewire. This is necessary because the diameter of a paddle lead does not allow two or three leads to be placed without rewiring the system. The success of placement was 42/43, with inability to access the epidural space in one patient in whom ligamentum flavum hypertrophy was present on the preoperative imaging study. In all patients, the system was placed at the L1-L2 level, or lower, based on the Food and Drug Administration labeling. The total numbers of leads placed were 75, with both paddle and percutaneous arrays implanted successfully. There were no adverse events during this prospective surveillance evaluation. Ten patients complained of soreness at the entry site and post-procedure stiffness. These complaints were treated with ice, rest, and analgesics and resolved without incident. CONCLUSION: This paper describes the initial US cases of the placement of a paddle lead via a minimally invasive percutaneous method, as well as complex cylindrical arrays with a single needle entry to the epidural space. The device functioned successfully and presented a safe option for placing paddle leads and complex arrays. PMID- 22296619 TI - Development of hypoxia enhanced 111In-labeled Bombesin conjugates: design, synthesis, and in vitro evaluation in PC-3 human prostate cancer. AB - The gastrin-releasing peptide receptor (BB2r) has shown great promise for tumor targeting due to the increase of the receptor expression in a variety of human cancers including prostate, breast, small-cell lung, and pancreatic cancer. From clinical investigations, prostate cancer has been shown to be among the most hypoxic of the cancers investigated. Many solid tumors contain regions of hypoxia due to poor organization and efficiency of the vasculature. However, hypoxia is typically not present in normal tissue. Nitroimidazoles, a thoroughly investigated class of hypoxia selective drugs, have been shown to be highly retained in hypoxic tissues. The purpose of this study is to determine if the incorporation of hypoxia trapping moieties into the structural paradigm of BB2r targeted peptides will increase the retention time of the agents in prostate cancer tumors. The present work involves the design, syntheses, purification, and in vitro investigation of hypoxia enhanced (111)In-BB2r-targeted radioconjugates. A total of four BB2r-targeted conjugates (1-4) were synthesized and coupled with increasing numbers of 2-nitroimidazoles, a hypoxia trapping moiety. Conjugates were radiolabeled with (111)In and purified by HPLC prior to in vitro studies. Receptor saturation assays under both normoxic and hypoxic conditions showed that the BB2r receptor expression on the PC-3 human prostate cancer cell line was not significantly affected by oxygen levels. Competitive binding assays revealed that incorporation of 2-nitroimidazoles had a detrimental effect to BB2r binding when adequate spacer groups, between the hypoxia trapping agent and the pharmacophore, were not employed. All of the 2-nitroimidazole containing BB2r-targeted agents exhibited significantly higher longitudinal retention in PC-3 cells under hypoxic conditions compared to the analogous normoxic studies. Protein association analysis revealed a 3-fold increase in binding of a 2-nitroimidazole containing BB2r-targeted agent under hypoxic relative to normoxic conditions. The positive nature of these results indicate that further exploration into the potential of hypoxia selective trapping agents for BB2r-targeted agents, as well as other targeted compounds, is warranted. PMID- 22296620 TI - Illegal treatment of barrows with nandrolone ester: effect on growth, histology and residue levels in urine and hair. AB - The effect of 17beta-19-nortestosterone (17betaNT) treatment of barrows on residue levels and growth was evaluated. Five barrows were treated three times during the fattening period with 17betaNT phenylpropionate (Nandrosol, nandrolone phenylpropionate 50 mg/ml,1 mg/kg body weight). Another five barrows were untreated and five boars (untreated) were kept as positive control. Boars and treated barrows showed a 13 and 9% improvement in growth compared to untreated barrows, with mean final body weights of 121.6, 117.8 and 109.0 kg, respectively. The bulbourethral glands of the treated barrows were three times heavier than untreated barrows. The histology of the prostate and bulbourethral gland of the treated barrows was comparable to the boars, whereas the control barrows showed atrophic glands. Levels of 17betaNT ester in hair from treated barrows were high, whereas boars and untreated barrows did not show levels above LLQ. It is concluded that analysis of hair can detect illegal treatment with 17betaNT ester in barrows. The size of the bulbourethral gland can also be used for screening in the slaughterhouse. PMID- 22296621 TI - Mitral regurgitation during a myocardial infarction--new predictors and prognostic significance at two years of follow-up. AB - AIMS: Ischemic Mitral Regurgitation (MR) has early prognostic impact in Myocardial Infarction (MI). Its medium-term importance, especially of mild MR, has not been established. PURPOSE: to determine new clinical/analytical predictors of MR in MI-patients and establish its prognostic value during two year follow-up [endpoints: mortality, decompensated heart failure (dHF)]. METHODS AND RESULTS: 796 patients admitted for MI (age 68.8+/-13.4, 63.2% males, 44.6% STEMI). DATA: Admission analytical study, risk scores, coronariography, pre discharge echocardiogram. Patients followed for two years. Clinical/analytical predictors of pre-discharge MR assessed. Predictive model for presence of pre discharge MR included GRACE for intra-hospital mortality [IHM](OR=1.008, p<0.001), glomerular filtration rate (GFR)[OR=0.993, p=0.048], admission haemoglobin (OR=0.84, p=0.003). In univariate analysis, moderate-severe MR predicted 2-year mortality (OR=3.32, p<0.001), but not dHF. Two year mortality rate was proportional to severity of pre-discharge MR. Mild MR (vs. no MR) associated with higher risk for 2-year mortality (OR=2.04, p=0.014) and re admission for dHF (OR=2.55, p=0.001). Predictive model for 2-year mortality included MR severity (OR=1.42, p=0.033) and GRACE for IHM (OR=1.023, p<0.001). CONCLUSION: GRACE score for IHM, GFR and admission haemoglobin independently predicted risk for pre-discharge MR. MR, including its milder form, was an independent predictor of 2-year mortality, adding prognostic power to GRACE score. PMID- 22296622 TI - Ultrafine structure of the hydroxyapatite amorphous phase in noninfectious phosphate renal calculi. AB - OBJECTIVE: We aimed to establish detailed morphology of the structureless amorphous hydroxyapatite (HAP) phase to improve our understanding of the formation mechanism of these concretions. Noninfectious phosphate renal calculi composed mainly of HAP consist of inorganic material in the form of spherules, in a seemingly structureless and amorphous phase and organic matter. METHODS: Several cross-sections of a fraction of phosphate renal stone composed solely of the amorphous HAP phase were examined with atomic force microscope. Both 2- and 3 dimensional images of their structure and nanoscale elastic modulus maps were obtained. RESULTS: The amorphous hap phase consists of 2 distinctly different morphologic forms of hydroxyapatite: separate and/or intergrown columnar crystals, and spherical agglomerates with diameters in the range 150-300 nm consisting of spherulites approximately 10 nm in diameter. The columnar crystals are irregularly disseminated in the stone interior, which is porous because of cavities with depths in excess of 100 nm. Organic matter is almost evenly distributed throughout the stone interior. CONCLUSION: Based on the observed calculus structure, the following mechanism of formation of the noninfectious phosphate calculi is suggested: Spherulites formed via the perikinetic aggregation of Posner's clusters present in urine supersaturated with respect to hydroxyapatite aggregate into spherical agglomerates that, after reaching a certain size, are retained in cavities with poor urodynamics, gradually settle, and become incorporated into developing concretion. The columnar crystals are probably nucleated on the detritus of organic origin embedded in the hydroxyapatite structureless phase. PMID- 22296623 TI - Ritonavir interacts with bortezomib to enhance protein ubiquitination and histone acetylation synergistically in renal cancer cells. AB - OBJECTIVE: To investigate the combined effects of the HIV protease inhibitor ritonavir and proteasome inhibitor bortezomib on renal cancer cells. Ritonavir induces endoplasmic reticulum (ER) stress and we hypothesized that inhibiting proteasome activity under ER stress would further inhibit cancer cell growth by enhancing protein ubiquitination. METHODS: The effectiveness of the combination of ritonavir and bortezomib on renal cancer cells (Caki-1, ACHN, 786-O, 769-P) was assessed by MTS assay, colony formation assay, cell cycle analysis, and annexin-V assay. In vivo efficacy was evaluated using mice subcutaneous tumor models. Induction of ER stress, protein ubiquitination, histone acetylation, and changes in the expression of histone deacetylase (HDAC) were evaluated by Western blotting. RESULTS: Ritonavir in combination with bortezomib induced apoptosis and inhibited renal cancer growth synergistically at clinically feasible concentrations. In subcutaneous tumor models using Caki-1 cells, 10-day treatment with the combination was well tolerated and inhibited tumor growth significantly. Ritonavir induced ER stress and the combination enhanced protein ubiquitination synergistically. The combination was also found to induce histone acetylation by suppressing the HDAC expression. CONCLUSION: The combination of ritonavir and bortezomib inhibits renal cancer growth synergistically. The effectiveness of the combination is caused by protein ubiquitination and histone acetylation. Our results provide a rationale for investigating the combination in patients with renal cancer. PMID- 22296624 TI - Assessment of the effects of a marine urban outfall discharge on caged mussels using chemical and biomarker analysis. AB - To assess the presence of endocrine disruptors in treated marine outfall discharges and their possible effects, mussels (Mytilus galloprovincialis) were caged in the environmental mixing zone of the outfall of the Santander sanitation system and in one control area. After 30, 60 and 90 days, samples were collected to perform chemical analyses (metals, anionic surfactants, alkylphenols, bisphenol A, phthalates and estrogenic hormones), biomarkers of general stress (lysosomal membrane stability-LMS, histopathology) and biomarkers of endocrine disruption (vitellogenin-like proteins and gonad index). There were no significant differences between outfall and control sites on contaminant levels, except for 4-tert-octylphenol which was higher in the outfall site. Bacteriological counts were higher in the outfall area. No relevant differences in biomarkers were detected between treated and control mussels. A significant reduction in LMS occurred in both groups after 90 days caging, indicating a stress situation possibly related to caging or to post-spawning reproductive state. PMID- 22296625 TI - Measuring the ecological integrity of an industrial district in the Amazon estuary, Brazil. AB - The aim of the present study is to provide information on the ecological integrity of an industrial district located in the estuary of Para River (Amazon estuary), by applying a selection of fish based multimetric indices of ecosystem integrity: Abundance Biomass Comparation (ABC); Biological Health Index; Estuarine Fish Community, Transitional Fish Classification and Estuarine Biotic Integrity Indexes. To evaluate the impacts of the industrial area and cargo terminal, three areas were considered: Zone 1, (maximum impact), Zone 2 (median risk) and Zone 3 (reference area). All the biological indices used were considered to be excellent indicators of the ecological integrity of the different sectors of the study area and were especially effective for the demonstration of the critical alterations of the fish community of Zone 1 and Zone 2. The simultaneous use of different indices family, with different assumptions, did strengthen the results enhancing the confidence in the diagnostic. PMID- 22296626 TI - Relation between body composition, abdominal obesity, and lung function. AB - Reference values of spirometry and diffusion capacity are usually adjusted for age, sex, height and ethnic origin. However, also other factors, mainly weight and body composition, have an effect on pulmonary function. Therefore, we examined how body composition and abdominal obesity are related to lung function in normal population and whether they should be taken into account in the reference values. Two hundred and eighty-four healthy Finnish non-smoking adults were included in the study. Height, waist circumference, abdominal sagittal diameter and body composition were measured, and spirometry and diffusion capacity (DLCO) were performed. Muscle mass (r = 0.29, P = 0.000) and lean body mass (r = 0.29, P = 0.000) correlated positively with DLCO. However, no significant correlation between body composition and spirometry results was observed. Abdominal sagittal diameter (r = -0.21, P = 0.000) and waist circumference (r = -0.22, P = 0.000) correlated inversely with the forced expiratory volume in 1 s/forced vital capacity ratio (FEV1/FVC). In our study population, subjects with higher muscle and lean body mass had higher DLCO. This indicates a need for future re-evaluation of reference values. Besides, already minor abdominal obesity is associated with obstructive changes in spirometry results. PMID- 22296627 TI - Component characteristics of thigh muscle volume in young and older healthy men. AB - The purpose of this study was to compare the component characteristics of thigh muscle volume in Japanese young and older men. The subjects in both young (YM, n = 15) and older (OM, n = 13) men were physically active (performed aerobic-type exercise 1-3 times per week), but none of the subjects had regularly participated in resistance training for a minimum of 3 years prior to the study. Contiguous transverse magnetic resonance imaging (1.5-T scanner) images were obtained from the thigh, and total and individual (quadriceps, hamstrings and adductors) muscle volumes were calculated by multiplying the muscle cross-sectional area (CSA) by slice thickness and the total number of slices. Muscle length and average muscle CSA (muscle volume divided by muscle length) were determined for each muscle. Maximum voluntary isometric (MVC) knee extension and flexion strength were measured, and muscle quality was defined as MVC per unit average muscle CSA (MVC/CSA). Quadriceps muscle volume and average CSA were, respectively, 20% and 16% lower (P < 0.05) in the OM than in the YM, while hamstrings and adductors muscle volumes and average CSA were similar in both groups. Knee extension and flexion MVC were lower (P < 0.05) in the OM than in the YM. Knee extensor MVC/CSA was similar in the two groups, while knee flexor MVC/CSA was lower (P < 0.05) in the OM than in the YM. Our results suggest that age-related thigh muscle volume loss is muscle specific, in that greater quadriceps muscle loss was found in the older group. PMID- 22296628 TI - Evaluation of gender differences in endothelium-independent dilation using peripheral arterial tonometry. AB - BACKGROUND: A change in peripheral arterial tonometry (PAT) in response to reactive hyperaemia is often used to provide a non-invasive measure of endothelium-dependent dilation (EDD). Reactive hyperaemia does not allow one to quantify endothelium-independent dilation (EID), which is part of overall vascular function. Although most research examining vascular function and cardiovascular disease has focused on EDD, there is evidence that cardiovascular risk factors may impair EID. PURPOSE: To examine the microvascular vasodilation response to nitroglycerin (NTG) in healthy adults using PAT. METHODS: Microvascular responses to reactive hyperaemia and NTG were evaluated in 86 (41 female and 45 male) healthy subjects (age 37 +/- 5 years). Beat-to-beat plethysmographic measurements of finger arterial pulse waves were recorded for 5 min following reactive hyperaemia. After a 10-min rest period, sublingual NTG (0.4 mg) was administered and PAT signal changes were measured for 10 min. Peak reactive hyperaemic index (RHI) and peak NTG-mediated index (NMI) were determined in all subjects. RESULTS: There were no significant gender differences in peak RHI (females: 2.07 +/- 0.56 versus males: 1.91 +/- 0.58, P = 0.20). Mean peak NMI for all subjects was 2.78 (+/- 1.49). Peak NMI was significantly greater in females than in males (3.11 +/- 1.59 versus 2.50 +/- 1.34, P = 0.05). Time to peak NMI was not significantly different between genders (7 min, 28 s [+/- 1 min, 47 s], versus 7 min, 14 s [+/- 1 min, 49 s], P = 0.58). CONCLUSION: In this population of healthy adults, peak NMI was significantly greater in females than in males. These findings suggest that gender differences exist in the microvascular vasodilation responses to NTG using PAT. PMID- 22296629 TI - Surface microdialysis sampling: a new approach described in a liver ischaemia model. AB - We recently have shown that samples from microdialysis (MD) probes placed on the surface of the heart reflect metabolic events in the myocardium. This new interesting observation challenges us to consider whether surface application of MD applies to other parenchymatous organs and their surfaces. In 13 anesthetized pigs, transient liver ischaemia was achieved by occlusion of arterial and venous inflow to the liver. Two probes on liver surface and two in parenchyma were perfused with a flow rate of 1 MUl per min (n = 13). An identical set-up was used for probes with a flow rate of 2 MUl per min (n = 9). Samples were collected for every 15-min period during 60 min of baseline, 45 min of ischaemia and 60 min of reperfusion. Lactate, glucose, pyruvate and glycerol were analysed in MD samples. We focused on relative changes in the present study. There was a strong agreement in relative lactate and glucose levels between probes placed on liver surface and those on parenchyma. No significant differences in relative changes in lactate and glucose levels were seen between samples from surface probes and probes in liver parenchyma during equilibration, baseline, ischaemia or reperfusion with a flow rate of 1 MUl per min. MD sampling applied on the liver surface is a new application area for the MD technique and may be used to monitor liver metabolism during both physiological and pathophysiological conditions. PMID- 22296630 TI - Acute effects on the ventricular function in Swedish snuffers: an echocardiographic study. AB - AIMS: Cigarettes and Swedish snuff contain nicotine, which influence the cardiovascular system. Cigarette smoke has been shown to give an acute impairment in diastolic heart parameters. The systolic and diastolic heart function in snuff users is not thoroughly enough investigated. The aim of this study was to investigate if Swedish snuff will give an acute decrease in systolic and diastolic heart parameters in the left and right ventricles in healthy Swedish snuffers. METHODS AND RESULTS: Thirty healthy volunteers were examined with echocardiography. The study involved recordings from four different times: before snuff intake, 5 and 30 min after intake and finally 30 min after snuff withdrawal. The systolic and diastolic heart parameters were collected with conventional echocardiographic methods. In addition, the heart frequency and blood pressure response were measured. The pulse and blood pressure response were significantly altered (P < 0.01) during the test. Left ventricular ejection fraction and the amplitudes of mitral and tricuspid annulus motion did not alter significantly. The main finding in the study was the significant decrease (P < 0.05) in several diastolic heart parameters for both the left and right ventricles. CONCLUSIONS: This study shows that snuff intake causes a significant decrease in E/A ratio and a delay in ventricular relaxation and therefore a decrease in diastolic heart function in the left and right ventricles. The mechanism behind these alterations is probably very complex, but a combination of nicotine effects and loading conditions is probably the main factor. PMID- 22296631 TI - A new automated method for analysis of rCBF-SPECT images based on the active shape algorithm: normal values. AB - Most nuclear medicine clinicians use only visual assessment when interpreting regional cerebral blood flow (rCBF) from single-photon emission computed tomography (SPECT) images in clinical practice. The aims of this study were to develop a new, easy to use, automated method for quantification of rCBF-SPECT and to create normal values by using the method on a normal population. We developed a 3-dimensional method based on a brain-shaped model and the active-shape algorithm. The method defines the surface shape of the brain and then projects the maximum counts 0-1.5 cm deep for designated surface points. These surface projection values are divided into cortical regions representing the different lobes and presented relative to the whole cortex, cerebellum or cerebellar maximum. (99m) Tc-hexa methyl propylene amine oxime (HMPAO) SPECT was performed on 30 healthy volunteers with a mean age of 74 years (range 64-98). The ability of the active-shape algorithm to define the shape of the brain was satisfactory when visually scrutinized. The results of the quantification show rCBF values in the frontal, temporal and parietal lobes of 87-88% using cerebellum as the reference. There were no significant differences in normal rCBF values between male and female subjects and only a weak relation between rCBF and age. In conclusion, our new automated method was able to quantify rCBF-SPECT images and create normal values in ranges as expected. Further studies are needed to assess the clinical value of this method and the normal values. PMID- 22296632 TI - Atherosclerotic plaques in the internal carotid artery and associations with lung function assessed by different methods. AB - BACKGROUND: Previous studies on associations between reduced lung function and cardiovascular disease (CVD) have mainly been based on forced expiratory volume in 1-s (FEV(1) ) and vital capacity (VC). This study examined potential associations between five different lung function variables and plaques in the internal carotid artery (ICA). METHODS: Subjects (n = 450) from a previous population-based respiratory questionnaire survey [current smokers without lower respiratory symptoms, subjects with a self-reported diagnosis of chronic obstructive pulmonary disease (COPD) and never-smokers without lower respiratory symptoms] were examined using spirometry, body plethysmography and measurements of diffusing capacity for CO (D(L,CO) ). Plaques in the ICA were assessed by ultrasonography. RESULTS: Two hundred and twenty subjects were current smokers, 139 ex-smokers and 89 never-smokers. COPD was diagnosed in 130 subjects (GOLD criteria). Plaques in the ICA were present in 231 subjects (52%). General linear analysis with adjustment for established risk factors for atherosclerosis, including C-reactive protein, showed that D(L,CO) was lower [77.4% versus 83.7% of predicted normal (PN), P = 0.014] and residual volume (RV) was higher (110.3% versus 104.8% of PN, P = 0.020) in subjects with than without plaques in the ICA. This analysis did not show any statistically significant association between plaques and FEV(1) or VC. CONCLUSION: The occurrence of plaques in the ICA was associated with low D(L,CO) and high RV, but not significantly with FEV(1) or COPD status. The results suggest that the relationships between reduced lung function, COPD and CVD are complex and not only linked to bronchial obstruction and low-grade systemic inflammation. PMID- 22296633 TI - The washout rate of a subcutaneous 99mTc-HSA depot in lower extremity lymphoedema. AB - PURPOSE: Lymphoscintigraphy is currently the leading diagnostic modality of lower extremity lymphoedema but has been criticized for being unreliable. Washout rate constants have been investigated and proven to be of diagnostic value in several studies of breast-cancer-related lymphoedema; however, the applicability in lower extremity lymphoedema needs further evaluation. The aim of the study was to verify if washout of (99m) Tc-human serum albumin ((99m) Tc-HSA) is a reliable diagnostic tool in lower extremity lymphoedema. METHODS: Twenty healthy volunteers and eight patients (11 legs) with lymphoscintigraphy verified lower extremity lymphoedema participated in the study. A depot consisting of 0.1 ml 10 MBq/ml (99m) Tc-HSA was injected subcutaneously into the dorsum of each foot. The depot washout rate was measured using a portable scintillation detector system and time-activity curves were generated. After 30 min of supine rest and 10 min of standardized ergometric exercise, measurements were recorded for 20 min. Following correction for physical decay of (99m) Tc, the depot washout rate constant was calculated using linear regression analysis. Finally depot half-life was calculated from the washout rate constant. RESULTS: Median half-life for healthy volunteers was 9.4 h (range 2.5-28.3 h). Median half-life for lymphoedema patients was 10.7 h (range 1.5-35.1 h). No statistical significant difference could be detected between healthy volunteers and lymphoedema patients (P = 0.78). CONCLUSIONS: The washout rate of a subcutaneous (99m) Tc-HSA depot is not a reliable diagnostic tool in examination of lower extremity lymphoedema. Additional examinations revealed in vivo instability of the utilized (99m) Tc-HSA as the likely reason. PMID- 22296634 TI - Ischaemic preconditioning reduces myocardial calcium overload in coronary occluded pig hearts shown by continuous in vivo assessment using microdialysis. AB - During ischaemia, ATP depletion leads to insufficient fuelling for Na(+) /K(+) ATPase, decreased electrochemical potential and increased influx of calcium ions. This study demonstrated a means to assess the effects of ischaemic preconditioning (IP) on the free intracellular Ca(2+) pool during prolonged ischaemia. In a porcine myocardial ischaemia model, microdialysis (MD) was used for sampling of metabolic and injury markers in IP and non-IP (control) groups. (45) Ca(2+) was delivered in microperfusate locally to ischaemic myocardium, with distribution and uptake assessed by (45) Ca(2+) recovery in microdialysate. Cardiomyocytes in vitro were exposed to a Ca(2+) ionophore and tested for (45) Ca(2+) uptake. An accentuated myocardial calcium ion influx (observed as an increased microdialysate (45) Ca(2+) recovery in the extracellular milieu) was noted in control pigs compared with IP pigs during ischaemia. Suspended cardiomyocytes preincubated with a Ca(2+) ionophore to increase the intracellular calcium ion pool and subsequently incubated with (45) Ca(2+) , displayed lower (45) Ca(2+) uptake in cells compared with control cells not exposed to the ionophore, corroborating the idea of a strong relationship between degree of intracellular calcium overload and microdialysate (45) Ca(2+) recovery. The ischaemic insult was differentially verified by metabolic and injury markers. We introduce an in vivo method for serial assessment of myocardial calcium overload during ischaemia, using a MD technique and (45) Ca(2+) inclusion. IP leads to relatively less calcium overload as assessed by this new method, and we interpret this to mean that reduction in calcium overload is an important part of the IP protective effect. PMID- 22296635 TI - Temporal 3D Lagrangian strain from 2D slice-followed cine DENSE MRI. AB - A quantitative analysis of myocardial mechanics is fundamental to the understanding of cardiac function, diagnosis of heart disease and assessment of therapeutic intervention. In clinical practice, most cardiac imaging analyses are performed in 2D because of the limited scan time available. However, the obtained information from a 2D measurement is limited. This study presents a method to obtain temporal evolutions of transmural 3D Lagrangian strains from two intersecting 2D planes of slice-followed cine displacement encoding with stimulated echoes (DENSE) data using a bilinear-cubic polynomial element to resolve strain from the displaced myocardial positions. The method was validated against an analytical standard and has been applied to in vivo data acquired on a 3 T magnetic resonance system from a healthy volunteer to quantify systolic strains at the anterior-basal region of left ventricular myocardium. The method demonstrates accurate results when validated in the analytical model, and the in vivo results agree within experimental accuracy with values reported in the literature. Even with a short scan time, this method provides the full 3D Lagrangian strain tensor from two 2D DENSE measurements. PMID- 22296636 TI - Effects of a brief Valsalva manoeuvre on hemodynamic response to strength exercises. AB - Strength training is a recommended measure against loss of strength and muscle mass because of age- or illness-induced inactivity. Strength exercises may impose heavy cardiovascular load by increasing heart rate and blood pressure. To increase strength efficiently, a heavy load has to be applied; this, however, leads to a spontaneous Valsalva manoeuvre, which additionally raises blood pressure. Avoidance of this manoeuvre is recommended. If the additional rise in arterial blood pressure caused by Valsalva manoeuvre is smaller than intrathoracic or intracranial pressures during this manoeuvre, Valsalva manoeuvre may actually protect arteries located in the thorax and in the brain by diminishing transmural pressure acting across these vessels. Effect of controlled breathing or brief Valsalva manoeuvre on arterial pressure at rest and during knee extension against 15-repetition maximum resistance was evaluated. In 12 healthy young men blood pressure was measured continuously and non-invasively, knee angle, speed of respiratory air or mouth pressure (MP) were continuously registered. Each combination of respiratory and exercise manoeuvres was repeated six times, for every of last three repetitions peak and trough systolic and diastolic pressure were determined. Strength exercises elevated peak pressures more than trough pressures, systolic more than diastolic. Valsalva manoeuvre increased only peak systolic and peak diastolic pressure. This increase was in average lesser than MP, thus rendering an argument in favour of protective role of brief Valsalva manoeuvre because of decline in transmural pressure acting on thoracic and possibly cerebral arteries. However, there was strong individual variability, and in few instances, arterial pressure increased because of brief Valsalva manoeuvre more than MP; thus in some subjects, the manoeuvre might enhance transmural pressure acting on thorax arteries. PMID- 22296637 TI - Impact of exercise on retinal microvascular regulation measured by dynamic vessel analysis in healthy individuals. AB - We assessed the acute impact of physical exercise on the retinal vessel diameter and the regulation of vasoconstriction and vasodilatation owing to flicker that has never been examined before. Forty young (mean age 24 years) healthy subjects (26 women and 14 men) had retinal examinations with dynamic vessel analysis prior and after (0.5, 1.5 and 2.5 h) intense exercise of 20 min. The measurements were always taken on continuous same eye, each with a 350-s permanent dynamic vascular analysis including three cycles of 20 s with 12.5-Hz flicker provocation of the retinal vessel analyser system (RVA) device. Blood pressure values were measured before and after the dynamic vessel analysis with a portable, automatic blood pressure monitor. Dynamic vessel analysis revealed that exercise had a substantial quickly and long-lasting effect on arterial and venous diameter (F = 30.38 and 35.85, P < 0.001) and arterial dilatation owing to flicker (F = 10.67, P < 0.005). The effect of flicker on arterial constriction was not significant for all time periods (F = 0.26). Friedman test revealed that arterial constriction to flicker was significantly increased at 30 and 90 min (chi(2) = 43.3 and 49.2, P < 0.001). Exercise had a significant effect on venous constriction and dilatation owing to flicker (F = 11.14, P < 0.001, F = 3.77, P < 0.05). Our results demonstrate that the expected impact of exercise can be accurately assessed with the RVA. We therefore suggest that the RVA is a valid instrument to assess early structural and functional alterations in the retinal vascular system. PMID- 22296638 TI - Heart rate variability in free diving athletes. AB - The aim of the study was to evaluate the cardiac autonomic activity in free diving (FD) athletes. Thirteen Greek male free divers (group I, aged 33.4 +/- 6.3 years, 6.6 +/- 4.5 years of training experience) volunteered to participate while 13 age-matched sedentary subjects served as control group (group II). All subjects were submitted to ambulatory 24-h ECG recording for heart rate variability (HRV) analysis on a day of regular activities with no exercise or training. The results showed that group I had significantly lower minimum and mean heart rate by 23.9% (P < 0.001) and 20.6% (P < 0.001), respectively. All the measured time and frequency domain indices of HRV which reflect cardiac parasympathetic activity were higher in group I than in group II by 37.6% to 146% (P < 0.001). Conclusively, the resting cardiac autonomic activity and especially the parasympathetic branch was significantly increased in free divers compared to untrained subjects. This finding should be rather attributed to the accumulated effect of both exercise training and frequent exposure to FD stimulus. PMID- 22296639 TI - Visible-light-mediated utilization of alpha-aminoalkyl radicals: addition to electron-deficient alkenes using photoredox catalysts. AB - Synthetic use of alpha-aminoalkyl radicals formed by single electron oxidation of amines is quite limited. Here we demonstrate addition of alpha-aminoalkyl radicals to electron-deficient alkenes by visible-light-mediated electron transfer using transition metal polypyridyl complexes as photocatalysts, via a sequential redox pathway. PMID- 22296640 TI - Large right coronary artery to left ventricular fistula. AB - Right coronary to left ventricular fistulas are rare. We report a patient who presented with unstable angina and was found to have a large right coronary to left ventricular fistula. PMID- 22296641 TI - A bile-inducible membrane protein mediates bifidobacterial bile resistance. AB - Bbr_0838 from Bifidobacterium breve UCC2003 is predicted to encode a 683 residue membrane protein, containing both a permease domain that displays similarity to transporters belonging to the major facilitator superfamily, as well as a CBS (cystathionine beta synthase) domain. The high level of similarity to bile efflux pumps from other bifidobacteria suggests a significant and general role for Bbr_0838 in bile tolerance. Bbr_0838 transcription was shown to be monocistronic and strongly induced upon exposure to bile. Further analysis delineated the transcriptional start site and the minimal region required for promoter activity and bile regulation. Insertional inactivation of Bbr_0838 in B. breve UCC2003 resulted in a strain, UCC2003:838(800) , which exhibited reduced survival upon cholate exposure as compared with the parent strain, a phenotype that was reversed when a functional, plasmid-encoded Bbr_0838 gene was introduced into UCC2003:838(800) . Transcriptome analysis of UCC2003:838(800) grown in the presence or absence of bile demonstrated that transcription of Bbr_0832, which is predicted to encode a macrolide efflux transporter gene, was significantly increased in the presence of bile, representing a likely compensatory mechanism for bile removal in the absence of Bbr_0838. This study represents the first in depth analysis of a bile-inducible locus in bifidobacteria, identifying a key gene relevant for bifidobacterial bile tolerance. PMID- 22296642 TI - Identification and characterization of reactive metabolites in natural products driven drug discovery. AB - Toxicity of natural products arising from their metabolic biotransformation into reactive chemical intermediates is an important reason for high attrition rates in early drug discovery efforts. Screening promising natural products for their likelihood to form such metabolites is therefore an important step in identifying potential liabilities in the drug development process. However, such screening is complicated by the need to have test methods that are sensitive, reliable, accurate, efficient, and cost-effective enough to allow for routine identification and characterization of the reactive metabolites. These metabolites are typically formed in minute quantities, usually through minor metabolic pathways, and, due to their highly reactive and therefore transient chemical nature, pose considerable analytical challenges in attempts to determine their properties. Understanding the formation of reactive metabolites may be used as the basis for synthetic chemical modification of parent natural products aimed at bypassing such harmful bioactivation. This paper highlights the general principles and protocols commonly used to predict and study the formation of reactive metabolites in vitro and how the data obtained from such studies can be used in the development of safer drugs from natural products. PMID- 22296643 TI - Photocatalyzed sulfide oxygenation with water as the unique oxygen atom source. AB - In our research program aiming to develop new ruthenium-based polypyridine catalysts for oxidation we were interested in combining a photosensitizer and a catalytic fragment within the same complex to achieve catalytic light-driven oxidation. To respond to the lack of such conjugates, we report here a new catalytic system capable of using light to activate water molecules in order to perform selective sulfide oxygenation into sulfoxide via an oxygen atom transfer from H(2)O to the substrate with a TON of up to 197 +/- 6. On the basis of electrochemical and photophysical studies, a proton-coupled electron-transfer process yielding to an oxidant Ru(IV)-oxo species was proposed. In particular, the synergistic effect between both partners in the dyad yielding a more efficient catalyst compared to the bimolecular system is highlighted. PMID- 22296644 TI - ATP13A2 mutations impair mitochondrial function in fibroblasts from patients with Kufor-Rakeb syndrome. AB - Mutations in ATP13A2 cause autosomal-recessive parkinsonism (Kufor-Rakeb syndrome; KRS). Because several other parkinsonism-associated proteins have been connected to mitochondrial function and mitophagy, we studied the impact of endogenous mutations in ATPase type 13A2 (ATP13A2) on mitochondria in fibroblasts from KRS patients compared with controls. In patients, we detected decreased adenosine triphosphate (ATP) synthesis rates, increased mitochondrial DNA levels, a higher frequency of mitochondrial DNA lesions, increased oxygen consumption rates, and increased fragmentation of the mitochondrial network. Importantly, overexpression of wild-type ATP13A2 rescued the respiration phenotype. These findings collectively suggest that ATP13A2 contributes to the maintenance of a healthy mitochondrial pool, supporting the hypothesis that impaired mitochondrial clearance represents an important pathogenic mechanism underlying KRS. PMID- 22296645 TI - Tumour necrosis factor receptor superfamily member 11B polymorphisms and association with knee osteoarthritis in women. AB - We examined single-nucleotide polymorphisms (SNPs) across the tumour necrosis factor receptor superfamily member 11B (TNFRSF11B) gene and knee OA. We identified alleles in a VNTR region in intron 3 that was observed exclusively in women OA cases (P = 0.007, Pc = 0.042). Our results reveal that a previously unreported association between a VNTR genotype in TNFRSF11B and knee OA in women. PMID- 22296646 TI - Disputing the ethics of research: the challenge from bioethics and patient activism to the interpretation of the Declaration of Helsinki in clinical trials. AB - In this paper we argue that the consensus around normative standards for the ethics of research in clinical trials, strongly influenced by the Declaration of Helsinki, is perceived from various quarters as too conservative and potentially restrictive of research that is seen as urgent and necessary. We examine this problem from the perspective of various challengers who argue for alternative approaches to what ought or ought not to be permitted. Key themes within this analysis will examine these claims and argue they have implications for the interests of the research subject, research governance and regulation. Using our work with TREAT-NMD, the neuromuscular clinical trials network, we posit that there is a place for advancing the discourse of moral rights and moral duties in the context of research, especially from the perspective of patients and their families, and for including the politics of patient activism and empowerment. At the same time we remain vigilant to the danger that the therapeutic misconception and other serious vulnerabilities for the patient population in clinical trials, are at risk of being overlooked. PMID- 22296647 TI - Insulinoma diagnosed in the postpartum: clinical and immunohistochemical features. AB - Insulinomas are rare pancreatic beta-cell tumors with an estimated incidence of 1:250.000 persons/year. We present a novel case of insulinoma manifesting immediately after childbirth. Eight days after delivery, a 21-year-old, previously healthy woman presented paresthesia in hands, upper and lower limbs muscle weakness with difficult walking, which worsened during breastfeeding sessions. Laboratory tests showed blood glucose levels between 37 and 55 mg/dL with inappropriately normal insulin levels (7.78 MUUI/mL; normal range: 5-29). An abdominal computed tomography showed a nodular lesion measuring 2 cm at the head of the pancreas. Tumor enucleation resulted in complete resolution of hypoglycemia. Histopathological and immunohistochemical analysis were consistent with an insulinoma. About 27 cases of insulinoma associated with pregnancy have been reported to date, mostly diagnosed before the 16th week. The beginning of symptoms soon after delivery is less common. Understanding the interactions between pancreatic beta-cell function and all the physiological metabolic and hormonal adaptations associated with gestation is essential for the adequate management of hypoglycemic disorders in pregnant women. PMID- 22296648 TI - An expert opinion on the current treatment of anemia in patients with kidney disease. AB - INTRODUCTION: Anemia, a frequent and early complication of chronic kidney disease (CKD), not only impairs quality of life but is also an independent risk factor for adverse cardiovascular outcomes. Erythropoiesis-stimulating agents (ESAs), together with iron, are the main therapeutic tool to correct anemia in CKD patients nowadays. AREAS COVERED: Following a literature search on PubMed using 'anemia', 'hemoglobin', 'erythropoietin' and 'target' as keywords, we critically analyzed ESAs, looking in depth at their distinct characteristics and possible advantages in the clinical setting. The introduction of biosimilars into the European market is also discussed. Finally, we reviewed current evidence about the optimal hemoglobin (Hb) target to aim at in CKD patients receiving ESA and possible treatment indications by international guidelines or health institutions. EXPERT OPINION: All ESAs are effective agents to correct anemia. Newer molecules have been developed with an improved pharmacokinetic and pharmacodynamic profile. This translates into longer administration intervals than can be a true advantage, mainly for CKD patients not receiving dialysis. Short-acting epoetins, including biosimilars, should be administered more often, but can be cheaper than last-generation molecules. Following publication of the TREAT study, there is considerable confusion about the optimal Hb target to aim for in CKD patients using ESA. While waiting for Kidney Disease Global Outcome (KDIGO) guidelines recommendations, we believe that the general approach to anemia management in CKD patients should still aim at Hb levels of 11 - 12 g/dl; however, it is wise to use caution in those patients who are hyporesponsive to ESA or have a previous history of stroke or malignancies. PMID- 22296649 TI - Physical modalities in the treatment of neurological dysfunction. AB - OBJECTIVE: This chapter presents modalities of physical therapy used in optimizing sensorimotor recovery from nervous system injury. METHODS: A brief historical perspective, rationale, indications for application, and evidence of effectiveness of various physical treatment modalities is provided. RESULTS: Many of the facilitatory and inhibitory techniques used in the past are no longer used, as they were based on an understanding of recovery after nervous system injury that is now outdated. There has been a paradigm shift in the management of people with neurological dysfunction. In particular there has been a reduction in focus on the positive features or the upper motor neuron syndrome, such as spasticity, and an increasing emphasis on active, task-related practice of functional tasks. CONCLUSION: Physical therapy for people with neurological disorders has undergone a paradigm shift as a result of new knowledge about motor control, skill acquisition, and recovery of function after injury. Future research should address new applications of electrical stimulation and whole body vibration as well as the optimal dosage and timing of interventions. PMID- 22296650 TI - Peripheral neuropathy response to erythropoietin in type 2 diabetic patients with mild to moderate renal failure. AB - This study assessed the added effect of 6 months of erythropoietin (EPO) administration in patients suffering from diabetic neuropathy with mild to moderate chronic kidney disease (CKD) managed with gabapentin. Twenty diabetic patients with mild to moderate CKD were included; 12 in gabapentin and 8 in EPO+gabapentin group. The subjects underwent nerve conduction studies (NCS) at the initiation of the investigation and after 6-month treatment. NCS were made in deep and superficial peroneal, tibial, and sural nerves. After 6 months, in both the groups, proximal motor latency (PML) nonsignificantly improved in deep peroneal and tibial nerves; conversely, dorsal motor latency (DML) got slightly impaired in these two nerves. A nonsignificant disruption and improvement was observed in deep peroneal and tibial motor nerve conduction velocity (MNCV), respectively, in gabapentin group. Although the F-wave of tibial and deep peroneal nerves remained stable in gabapentin group, a nonsignificant improvement was observed in EPO+gabapentin group. H-reflex of tibial nerve and all the evaluated parameters of sural and superficial peroneal nerves remained constant in all patients. Thus, it can be concluded that 6-month administration of EPO+gabapentin, or gabapentin alone in mild to moderate CKD patients with diabetic neuropathy could not improve nerve performance. PMID- 22296651 TI - Unusual CNS presentation of thyroid cancer. AB - As advanced therapies allow cancer patients to live longer, disease failure in the central nervous system increases from limited therapeutic penetration. Primary thyroid malignancies rarely metastasize to the brain and have a small number of investigations in literature on the subject. The majority of brain metastases involve the brain parenchyma, reflecting the mass and blood distribution within the brain and central nervous system. Here, we report two cases of the most common differentiated thyroid cancers; follicular thyroid cancer having brain involvement from extra-axial growth and papillary thyroid cancer having brain involvement from a single intraventricular metastasis, presumed as metastasis from the vascular choroid plexus. Both of our cases had widespread systemic involvement. For our follicular thyroid cancer, brain involvement was a result of extra-axial growth from cavarial bone, and our papillary thyroid cancer had brain involvement from a single intraventricular metastasis that was initially resected and nearly a year later developed extensive brain involvement. Unlike the usual gray-white junction metastases seen in the majority of metastatic brain tumors, including thyroid, our cases are uncommon. They reflect differences in tumor biology that allows for spread and growth in the brain. Although there is growing genetic knowledge on tumors that favor brain metastases, little is known about tumors that rarely involve the brain. PMID- 22296652 TI - ROS-mediated killing efficiency with visible light of bacteria carrying different red fluorochrome proteins. AB - Red fluorescent proteins can generate reactive oxygen species (ROS) if their fluorochrome is stimulated e.g. by visible light illumination. ROS compounds have very reactive, highly toxic properties leading to cell damage which results in cell killing. In this context, the toxicity of the various red fluorochromes KillerRed, DsRed2, mCherry, and mRFP expressed in Escherichia coli bacteria was tested after illumination with white light. The toxic effect was determined by measurement of the colony forming ability 24h after transfection and illumination. KillerRed was found to be the most harmful, followed by mRFP and DsRed2 while bacteria expressing mCherry and controls without fluorescent proteins survived after application of identical illumination doses. Their application and a possible bactericide role is discussed. PMID- 22296653 TI - Simultaneous determination of stilbenes, phenolic acids, flavonoids and anthraquinones in Radix polygoni multiflori by LC-MS/MS. AB - A simple and sensitive method was developed for the simultaneous determination of stilbenes, phenolic acid, flavonoids and anthraquinones in Radix polygoni multiflori by liquid chromatography tandem mass spectrometry (LC-MS/MS). The separation was completed on an Eclipse Plus C(18) (50 mm * 3.0 mm, 1.8 MUm) column using 0.05% (v/v) formic acid and acetonitrile as mobile phases. The correlation coefficients of all the calibration curves were higher than 0.9990. The recoveries ranged from 95.9% to 106%. Relative standard deviations of intra and inter-day precisions were lower than 6.51%. The validated method was successfully applied to quantify stilbenes, phenolic acid, flavonoids and anthraquinones, which provided a new basis for overall assessment on quality of Radix polygoni multiflori. PMID- 22296654 TI - HPLC-PDA method for quinovic acid glycosides assay in Cat's claw (Uncaria tomentosa) associated with UPLC/Q-TOF-MS analysis. AB - Uncaria tomentosa (Willd.) is a medicinal plant largely used in folk medicine due to its wide range of biological activities, many of which are usually ascribed to the two main classes of secondary metabolites, namely, alkaloids and quinovic acid glycosides. In this work, a reversed phase HPLC-PDA method was developed and validated for the assay of quinovic acid glycosides in crude and dried extracts of Uncaria tomentosa (Cat's claw) bark. The validation comprised tests of specificity, accuracy, linearity, intermediate precision, repeatability and limits of detection and of quantification. Alpha-hederin was used as the external standard. High coefficients of determination with lower R.S.D. were achieved for both external standard and crude extract. The structural characterization of the main quinovic acid glycosides presented in the crude extract was carried out through UPLC/Q-TOF-MS. The identities of the compounds were obtained through the comparison of their fragmentation patterns with those reported in the literature. The analytical method was successfully applied for quantifying quinovic acid glycosides in two different dried extracts from U. tomentosa and in one quinovic acid glycosides purified fraction. PMID- 22296655 TI - Abdominal ultrasonographic findings at diagnosis of osteosarcoma in dogs and association with treatment outcome. AB - The purpose of this study was to describe abdominal ultrasonographic findings present at diagnosis of osteosarcoma (OSA) in dogs and to investigate for associations with treatment outcome. Medical records from 118 dogs diagnosed with OSA that had abdominal ultrasonography performed as part of their initial evaluation were reviewed. Fifty-seven percent had ultrasonographic abnormalities identified. The organ with the highest frequency of ultrasonographic changes was the spleen. While most sonographic changes were considered to be either benign or of unknown clinical consequences, metastases were identified in three dogs (2.5%), two of which (1.7%) did not have other evidence of metastasis. Dogs with any ultrasonographic abnormality were less likely to receive definitive therapy (P = 0.005) and exhibited shorter survival, although the latter observation was not statistically significant (P = 0.071). However, the identification of lesions in either the liver (P = 0.021) or the kidney (P = 0.003) was statistically associated with shorter survival. PMID- 22296656 TI - Aryl methyl sulfides as substrates for rhodium-catalyzed alkyne carbothiolation: arene functionalization with activating group recycling. AB - A Rh(I)-catalyzed method for the efficient functionalization of arenes is reported. Aryl methyl sulfides are combined with terminal alkynes to deliver products of carbothiolation. The overall process results in reincorporation of the original arene functional group, a methyl sulfide, into the products as an alkenyl sulfide. The carbothiolation process can be combined with an initial Rh(I)-catalyzed alkene or alkyne hydroacylation reaction in three-component cascade sequences. The utility of the alkenyl sulfide products is also demonstrated in simple carbo- and heterocycle-forming processes. We also provide mechanistic evidence for the course of this new process. PMID- 22296658 TI - Permanent genetic resources added to Molecular Ecology Resources Database 1 October 2011-30 November 2011. AB - This article documents the addition of 139 microsatellite marker loci and 90 pairs of single-nucleotide polymorphism sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Aglaoctenus lagotis, Costus pulverulentus, Costus scaber, Culex pipiens, Dascyllus marginatus, Lupinus nanus Benth, Phloeomyzus passerini, Podarcis muralis, Rhododendron rubropilosum Hayata var. taiwanalpinum and Zoarces viviparus. These loci were cross-tested on the following species: Culex quinquefasciatus, Rhododendron pseudochrysanthum Hay. ssp. morii (Hay.) Yamazaki and R. pseudochrysanthum Hayata. This article also documents the addition of 48 sequencing primer pairs and 90 allele-specific primers for Engraulis encrasicolus. PMID- 22296659 TI - The quest for equity in Latin America: a comparative analysis of the health care reforms in Brazil and Colombia. AB - INTRODUCTION: Brazil and Colombia have pursued extensive reforms of their health care systems in the last couple of decades. The purported goals of such reforms were to improve access, increase efficiency and reduce health inequities. Notwithstanding their common goals, each country sought a very different pathway to achieve them. While Brazil attempted to reestablish a greater level of State control through a public national health system, Colombia embraced market competition under an employer-based social insurance scheme. This work thus aims to shed some light onto why they pursued divergent strategies and what that has meant in terms of health outcomes. METHODS: A critical review of the literature concerning equity frameworks, as well as the health care reforms in Brazil and Colombia was conducted. Then, the shortfall inequality values of crude mortality rate, infant mortality rate, under-five mortality rate, and life expectancy for the period 1960-2005 were calculated for both countries. Subsequently, bivariate and multivariate linear regression analyses were performed and controlled for possibly confounding factors. RESULTS: When controlling for the underlying historical time trend, both countries appear to have experienced a deceleration of the pace of improvements in the years following the reforms, for all the variables analyzed. In the case of Colombia, some of the previous gains in under five mortality rate and crude mortality rate were, in fact, reversed. CONCLUSIONS: Neither reform seems to have had a decisive positive impact on the health outcomes analyzed for the defined time period of this research. This, in turn, may be a consequence of both internal characteristics of the respective reforms and external factors beyond the direct control of health reformers. Among the internal characteristics: underfunding, unbridled decentralization and inequitable access to care seem to have been the main constraints. Conversely, international economic adversities, high levels of rural and urban violence, along with entrenched income inequalities seem to have accounted for the highest burden among external factors. PMID- 22296660 TI - Social network analysis and agent-based modeling in social epidemiology. AB - The past five years have seen a growth in the interest in systems approaches in epidemiologic research. These approaches may be particularly appropriate for social epidemiology. Social network analysis and agent-based models (ABMs) are two approaches that have been used in the epidemiologic literature. Social network analysis involves the characterization of social networks to yield inference about how network structures may influence risk exposures among those in the network. ABMs can promote population-level inference from explicitly programmed, micro-level rules in simulated populations over time and space. In this paper, we discuss the implementation of these models in social epidemiologic research, highlighting the strengths and weaknesses of each approach. Network analysis may be ideal for understanding social contagion, as well as the influences of social interaction on population health. However, network analysis requires network data, which may sacrifice generalizability, and causal inference from current network analytic methods is limited. ABMs are uniquely suited for the assessment of health determinants at multiple levels of influence that may couple with social interaction to produce population health. ABMs allow for the exploration of feedback and reciprocity between exposures and outcomes in the etiology of complex diseases. They may also provide the opportunity for counterfactual simulation. However, appropriate implementation of ABMs requires a balance between mechanistic rigor and model parsimony, and the precision of output from complex models is limited. Social network and agent-based approaches are promising in social epidemiology, but continued development of each approach is needed. PMID- 22296661 TI - From red to white urine: a patient's nightmare with a rather benign outcome. AB - BACKGROUND: Chyluria is a medical condition with presence of chyle in the urine. The disease is most prevalent in endemic regions of Africa and the Indian subcontinent where it is mostly caused by parasitic infections, particularly lymphatic filariasis due to wucheria bancrofti. Non-parasitic chyluria, however, is a very rare finding. CASE PRESENTATION: We report the case of a 48 year old woman who developed a lymphorenal fistula with chyluria following ureterrenoscopy with biopsies taken for urological work-up of persistent macrohematuria. Renal biopsy confirmed the diagnosis of benign familial hematuria due to thin basement nephropathy, a condition frequently associated with episodes of macrohematuria. CONCLUSIONS: This case highlights a rare case of non-parasitic chyluria as a complication of urological work-up for macrohematuria of benign nature. PMID- 22296662 TI - Genotyping for cytokine polymorphisms in a Northern Ivory Coast population reveals a high frequency of the heterozygote genotypes for the TNF-alpha-308G/A SNP. AB - Cytokine polymorphisms influence the outcomes of parasitic diseases and vary among populations because of their different evolutionary histories and selective pressures imposed by host-pathogen interactions. In this frame, we investigated the frequencies of TNF-alpha (-308G/A), TGF-beta(1) (codon 10C/T, codon 25C/G) and IL-10 (-1082A/G) SNPs in 133 individuals from Ouangolodougou, a rural village in Northern Ivory Coast, where malaria and other parasitic diseases are endemic. The SNPs alleles were determined by ARMS-PCR methodology. Allele frequencies of the SNPs investigated were as follows: IL 10 -1082G = 0.741 and -1082A = 0.259; TGF-beta(1) Codon 10 C = 0.835 and T = 0.165; TGF-beta(1) Codon 25 G = 0.782 and C = 0.218. For the TNF-alpha gene, we found high frequencies of the -308A allele (0.305) and heterozygote genotypes (0.594), with a consequent deviation from the Hardy-Weinberg equilibrium. The high heterozygosity at the TNF-alpha locus suggests a possible selective advantage of the heterozygote genomes, associated with intermediate levels of TNF-alpha expression, against the infectious agents endemic in Western Africa. PMID- 22296664 TI - Mathematical modeling and comparison of protein size distribution in different plant, animal, fungal and microbial species reveals a negative correlation between protein size and protein number, thus providing insight into the evolution of proteomes. AB - BACKGROUND: The sizes of proteins are relevant to their biochemical structure and for their biological function. The statistical distribution of protein lengths across a diverse set of taxa can provide hints about the evolution of proteomes. RESULTS: Using the full genomic sequences of over 1,302 prokaryotic and 140 eukaryotic species two datasets containing 1.2 and 6.1 million proteins were generated and analyzed statistically. The lengthwise distribution of proteins can be roughly described with a gamma type or log-normal model, depending on the species. However the shape parameter of the gamma model has not a fixed value of 2, as previously suggested, but varies between 1.5 and 3 in different species. A gamma model with unrestricted shape parameter described best the distributions in ~48% of the species, whereas the log-normal distribution described better the observed protein sizes in 42% of the species. The gamma restricted function and the sum of exponentials distribution had a better fitting in only ~5% of the species. Eukaryotic proteins have an average size of 472 aa, whereas bacterial (320 aa) and archaeal (283 aa) proteins are significantly smaller (33-40% on average). Average protein sizes in different phylogenetic groups were: Alveolata (628 aa), Amoebozoa (533 aa), Fornicata (543 aa), Placozoa (453 aa), Eumetazoa (486 aa), Fungi (487 aa), Stramenopila (486 aa), Viridiplantae (392 aa). Amino acid composition is biased according to protein size. Protein length correlated negatively with %C, %M, %K, %F, %R, %W, %Y and positively with %D, %E, %Q, %S and %T. Prokaryotic proteins had a different protein size bias for %E, %G, %K and %M as compared to eukaryotes. CONCLUSIONS: Mathematical modeling of protein length empirical distributions can be used to asses the quality of small ORFs annotation in genomic releases (detection of too many false positive small ORFs). There is a negative correlation between average protein size and total number of proteins among eukaryotes but not in prokaryotes. The %GC content is positively correlated to total protein number and protein size in prokaryotes but not in eukaryotes. Small proteins have a different amino acid bias than larger proteins. Compared to prokaryotic species, the evolution of eukaryotic proteomes was characterized by increased protein number (massive gene duplication) and substantial changes of protein size (domain addition/subtraction). PMID- 22296665 TI - Growth mechanisms of endometriotic cells in implanted places: a review. AB - Endometriosis is a common gynecological disease defined by extrauterine growth of endometrial glands and stroma. A variety of theories have been proposed to account for the pathogenesis of this disease, including retrograde transplantation theory, metaplasia of coelomic epithelium, hematogenic and lymphogenic spread, and remnants of the Mullerian duct. However, the etiopathology of endometriosis is still obscure. In this article, we aim to summarize recent researches concerning the growth mechanisms of endometriotic cells in implanted sites systematically, including the adhesion, invasion, angiogenesis, proliferation, apoptosis of endometriotic cells, variations of the immune molecules and endometriotic cells themselves, which may provide clues for future researches in the pathogenesis of endometriosis. PMID- 22296666 TI - 'Ethics is for bad guys!' Putting the 'moral' into moral enhancement. PMID- 22296667 TI - Clinical, histopathological and immunohistochemical characterization of canine indolent lymphoma. AB - Indolent lymphoma comprises up to 29% of all canine lymphoma; however, limited information exists regarding the subtypes and biological behaviour. This retrospective study describes the clinical characteristics, histopathological and immunohistochemical features, treatment, outcome and prognostic factors for 75 dogs with indolent lymphoma. WHO histopathological classification and immunohistochemistry (IHC) for CD79a, CD3, Ki67 and P-glycoprotein (P-gp) was performed. The most common histopathological subtype was T-zone, 61.7%, (MST 33.5 months), followed by marginal zone, 25%, (MST 21.2 months), P = 0.542. The addition of IHC to preliminary histopathological classification resulted in a revised diagnosis in 20.4% of cases. The use of systemic treatment did not influence survival, P = 0.065. Dogs treated with chlorambucil and prednisone did not reach a MST, compared with a MST of 21.6 months with CHOP-based chemotherapy, P = 0.057. The overall MST of 4.4 years confirms that this is indeed an indolent disease. However, the effect of systemic treatment must be determined through prospective trials. PMID- 22296668 TI - Targeting and maturation of Erv1/ALR in the mitochondrial intermembrane space. AB - The interaction of Mia40 with Erv1/ALR is central to the oxidative protein folding in the intermembrane space of mitochondria (IMS) as Erv1/ALR oxidizes reduced Mia40 to restore its functional state. Here we address the role of Mia40 in the import and maturation of Erv1/ALR. The C-terminal FAD-binding domain of Erv1/ALR has an essential role in the import process by creating a transient intermolecular disulfide bond with Mia40. The action of Mia40 is selective for the formation of both intra and intersubunit structural disulfide bonds of Erv1/ALR, but the complete maturation process requires additional binding of FAD. Both of these events must follow a specific sequential order to allow Erv1/ALR to reach the fully functional state, illustrating a new paradigm for protein maturation in the IMS. PMID- 22296669 TI - Dynamic photoswitching of helical inversion in liquid crystals containing photoresponsive axially chiral dopants. AB - Chirality switching is intriguing for the dynamic control of the electronic and optical properties in nanoscale materials. The ability to photochemically switch the chirality in liquid crystals (LCs) is especially attractive given their potential applications in electro-optic displays, optical data storage, and the asymmetric synthesis of organic molecules and polymers. Here, we present a dynamic photoswitching of the helical inversion in chiral nematic LCs (N*-LCs) that contain photoresponsive axially chiral dopants. Novel photoresponsive chiral dithienylethene derivatives bearing two axially chiral binaphthyl moieties are synthesized. The dihedral angle of the binaphthyl rings changes via the photoisomerization between the open and closed forms of the dithienylethene moiety. The N*-LCs induced by the dithienylethene derivatives that are used as chiral dopants exhibit reversible photoswitching behaviors, including a helical inversion in the N*-LC and a phase transition between the N*-LC and the nematic LC. The present compounds are the first chiral dopants that induce a helical inversion in N*-LC via the photoisomerization between open and closed forms of the dithienylethene moiety. PMID- 22296670 TI - Resistance to classical scrapie in experimentally challenged goats carrying mutation K222 of the prion protein gene. AB - Susceptibility of sheep to scrapie, a transmissible spongiform encephalopathy of small ruminants, is strongly influenced by polymorphisms of the prion protein gene (PRNP). Breeding programs have been implemented to increase scrapie resistance in sheep populations; though desirable, a similar approach has not yet been applied in goats. European studies have now suggested that several polymorphisms can modulate scrapie susceptibility in goats: in particular, PRNP variant K222 has been associated with resistance in case-control studies in Italy, France and Greece. In this study we investigated the resistance conferred by this variant using a natural Italian goat scrapie isolate to intracerebrally challenge five goats carrying genotype Q/Q 222 (wild type) and five goats carrying genotype Q/K 222. By the end of the study, all five Q/Q 222 goats had died of scrapie after a mean incubation period of 19 months; one of the five Q/K 222 goats died after 24 months, while the other four were alive and apparently healthy up to the end of the study at 4.5 years post-challenge. All five of these animals were found to be scrapie negative. Statistical analysis showed that the probability of survival of the Q/K 222 goats versus the Q/Q 222 goats was significantly higher (p = 0.002). Our study shows that PRNP gene mutation K222 is strongly associated with resistance to classical scrapie also in experimental conditions, making it a potentially positive target for selection in the frame of breeding programs for resistance to classical scrapie in goats. PMID- 22296671 TI - Superantigen profiles of emm and emm-like typeable and nontypeable pharyngeal streptococcal isolates of South India. AB - BACKGROUND: The major virulence factors determining the pathogenicity of streptococcal strains include M protein encoded by emm and emm-like (emmL) genes and superantigens. In this study, the distribution of emm, emmL and superantigen genes was analyzed among the streptococcal strains isolated from the patients of acute pharyngitis. METHODS: The streptococcal strains were isolated from the throat swabs of 1040 patients of acute pharyngitis. The emm and emmL genes were PCR amplified from each strain and sequenced to determine the emm types. The dot blot hybridization was performed to confirm the pathogens as true emm nontypeable strains. The presence of eleven currently known superantigens was determined in all the strains by multiplex PCR. RESULTS: Totally, 124 beta-hemolytic streptococcal strains were isolated and they were classified as group A streptococcus (GAS) [15.3% (19/124)], group C streptococcus (GCS) [59.7% (74/124)] and group G streptococcus (GGS) [25.0% (31/124)]. Among 124 strains, only 35 strains were emm typeable and the remaining 89 strains were emm nontypeable. All GAS isolates were typeable, whereas most of the GCS and GGS strains were nontypeable. These nontypeable strains belong to S. anginosus [75.3% (67/89)] and S. dysgalactiae subsp. equisimilis [24.7% (22/89)]. The emm and emmL types identified in this study include emm12.0 (28.6%), stG643.0 (28.6%), stC46.0 (17.0%), emm30.11 (8.5%), emm3.0 (2.9%), emm48.0 (5.7%), st3343.0 (2.9%), emm107.0 (2.9%) and stS104.2 (2.9%). Various superantigen profiles were observed in typeable as well as nontypeable strains. CONCLUSIONS: Multiplex PCR analysis revealed the presence of superantigens in all the typeable strains irrespective of their emm types. However, the presence of superantigen genes in emm and emmL nontypeable strains has not been previously reported. In this study, presence of at least one or a combination of superantigen coding genes was identified in all the emm and emmL nontypeable strains. Thus, the superantigens may inevitably play an important role in the pathogenesis of these nontypeable strains in the absence of the primary virulence factor, M protein. PMID- 22296672 TI - Combination antiretroviral therapy and chronic HIV infection affect serum retinoid concentrations: longitudinal and cross-sectional assessments. AB - BACKGROUND: Several lines of evidence suggest that retinoids (retinol-ROL or vitamin A, and its active metabolites, retinoic acids-RAs) play important pathogenic roles in HIV infection and combination antiretroviral therapy (cART) related events. We previously reported that antiretrovirals alter RAs synthesis in vitro. We hypothesised that in vivo serum retinoid concentrations are affected by both cART and HIV infection. This might explain several clinical and laboratory abnormalities reported in HIV-infected patients receiving cART. METHODS: The effects of optimal cART and chronic HIV on serum retinoids were firstly assessed longitudinally in 10 HIV-infected adults (group1 = G1): twice while on optimal cART (first, during long-term and second, during short term cART) and twice during 2 cART interruptions when HIV viral load (VL) was detectable. Retinoid concentrations during optimal long term cART in G1 were compared with cross-sectional results from 12 patients (G2) with suboptimal cART (detectable VL) and from 28 healthy adults (G3). Serum retinoids were measured by HPLC with ultraviolet detection. Retinoid concentrations were correlated with VL, CD4+ T- cell count and percentages, CD8+38+ fluorescence, triglycerides, cholesterol and C-peptide serum levels. RESULTS: During optimal cART, G1 participants had drastically reduced RAs (0.5 +/- 0.3 MUg/dL; P < 0.01) but the highest ROL (82 +/- 3.0 MUg/dL) concentrations. During cART interruptions in these patients, RAs slightly increased whereas ROL levels diminished significantly (P < 0.05). G3 had the highest RAs levels (7.2 +/- 1.1 MUg/dL) and serum ROL comparable to values in North Americans. Serum ROL was decreased in G2 (37.7 +/- 3.2 MUg/dL; P < 0.01). No correlations were noted between RA and ROL levels or between retinoid concentrations and CD4+ T- cell count, CD8+38+ fluorescence, VL. ROL correlated with triglycerides and cholesterol in G1 (rs = 0.8; P = 0.01). CONCLUSIONS: Serum RAs levels are significantly diminished by cART, whereas ROL concentrations significantly decreased during uncontrolled HIV infection but augmented with optimal cART. These alterations in retinoid concentrations may affect the expression of retinoid-responsive genes involved in metabolic, hormonal and immune processes and be responsible for some adverse events observed in HIV-infected persons treated with antiretrovirals. Further studies should assess concomitant serum and intracellular retinoid levels in different clinical situations in larger, homogenous populations. PMID- 22296673 TI - Concentrations of plasma metabolites, hormones, and mRNA abundance of adipose leptin and hormone-sensitive lipase in ketotic and nonketotic dairy cows. AB - BACKGROUND: Ketosis is an important metabolic disorder of dairy cows during the transition period. There have been many reports on the etiology of ketosis in periparturient cows, but little is known about its molecular etiology. OBJECTIVES: The objective of this study was to clarify the status of fat mobilization and mRNA abundance of leptin and hormone-sensitive lipase in cows with spontaneous clinical ketosis. ANIMALS: Ten ketotic Holstein cows and 10 nonketotic Holstein cows were used as the experimental animals. METHODS: Six blood biochemical parameters were evaluated by means of individual analysis method for 2 groups of cows. The mRNA abundance of leptin and hormone-sensitive lipase in tail fat tissue from 2 groups of cows was measured by real-time (RT) PCR, with a fluorescent Taqman probe and a standard curve. RESULTS: The plasma concentrations of glucose (P = 0.01), and leptin (P = 0.03), insulin (P = 0.05), and the ratio of insulin to glucagon (P = 0.04) were lower in ketotic compared with nonketotic cows, whereas there were marked increases in the plasma concentrations of nonesterified fatty acid and beta-hydroxybutyric acid (P = 0.005). The mRNA abundance of leptin (P = 0.04) and hormone-sensitive lipase (P = 0.02) in the fat tissue of ketotic cows was lower relative to that of nonketotic cows. CONCLUSIONS AND CLINICAL IMPORTANCE: The ketotic cows showed characteristics of type I ketosis and some adaptive changes to negative energy balance in the plasma leptin concentration and mRNA abundance of fat leptin and hormone-sensitive lipase. PMID- 22296674 TI - Patterns of aberrant DNA hypermethylation in nasopharyngeal carcinoma in Tunisian patients. AB - BACKGROUND: Aberrant methylation in the promoter of tumor-related genes is associated closely with epigenetically mediated gene silencing. The aim of the present study was to evaluate the methylation profile of Tunisian nasopharyngeal carcinoma (NPC) and to determine the clinicopathological features of tumors showing this epigenetic alteration. METHODS: Thirty-six archival NPC biopsies were investigated in comparison with 19 non-tumor nasopharyngeal tissue specimens. DNA methylation status of ten tumor-suppressor and related genes was analyzed by using methylation-specific PCR. The Epstein-Barr virus (EBV) presence was verified by PCR and in situ hybridization and the LMP1 oncoprotein expression was analyzed by immunohistochemistry. Findings were then correlated with clinicopathological variables (Patients' gender and age, tumor histological subtype and stage). RESULTS: Hypermethylation frequencies of the investigated genes in NPC biopsies were 75% for RASSFIA, 58.3% for SHP1, 47.2% for DAPK, 33.3% for P16, 31% for RARbeta2, 19.4% for GSTP1 and TIMP3, 11% for APC and CDH1, and 5.5% for MGMT. In non-tumor nasopharyngeal samples, hypermethylation was detected in lower frequencies in 6 genes (SHP 26.3%, P16 21%, RARbeta2 21%, DAPK 15.8%, TIMP3 10.5%, and GSTP 5.3%). Hypermethylation of RARbeta2 promoter was more frequent in tumors with lymph node metastasis than those without metastasis (43.5% vs 0%, p=0.03). Methylation of RASSF1A was more frequently detected in non keratinizing NPC than in undifferentiated subtype (100% vs 66.7%; p=0.05). A trend toward positive association was found between an increased number of methylated genes and LMP1 expression (p=0.07). However, no significant association was found for the remaining variables. CONCLUSIONS: This study indicates that hypermethylation of multiple genes is a common alteration in nasopharyngeal carcinomas in Tunisian patients and that this epigenetic change may play a role in the nasopharyngeal carcinogenesis. PMID- 22296675 TI - The role of resistin in colorectal cancer. AB - BACKGROUND: To date the role of resistin in colorectal cancer (CRC) is far from being elucidated. The aim of this study was to investigate the association between serum resistin levels and CRC in relation to known risk/protective factors including anthropometric, metabolic, inflammatory parameters as well as lifestyle individual characteristics. METHODS: 40 CRC patients and 40 controls were enrolled. Body weight, height, waist circumference and blood pressure were recorded. Fasting plasma glucose, lipids, C-reactive protein (CRP) and resistin levels were measured. Metabolic Syndrome (MS) was defined according to the harmonized definition. RESULTS: Resistin levels were significantly higher in CRC patients than in controls (p=0.028) and gradually increased with tumor stage progression (p=0.042). A high resistin level was statistically significant determinant of CRC after adjusting for age, sex, body mass index and lifestyle parameters (p=0.029). Resistin showed a strong association with CRP levels (p <= 0.0001). In stepwise regression analysis CRP remained the only independent predictor of both resistin levels (p=0.001) and CRC risk (p=0.021). CONCLUSIONS: These results clarify the nature of the association between resistin and CRC risk suggesting that the proinflammatory state of cancer, rather than the clinical diagnosis of CRC itself or its link with obesity and MS, may govern this association. PMID- 22296676 TI - Optimized nLC-MS workflow for laser capture microdissected breast cancer tissue. AB - Reliable sample preparation is of utmost importance for comparative proteome analysis, particularly when investigating minute amounts of clinical specimens, such as laser capture microdissected tumor tissue. In this study, we present an optimized nanoLC-MS workflow specifically for the analysis of laser capture microdissected breast cancer tissue. Analytical performance of different laser capture microdissection (LCM) functions available on the PALM system, time dependent trypsin digestion efficiency, effect of sample preparation and digestion time on peptide modification, semi-tryptic peptides and missed cleavages were evaluated. Our results show that microdissection from uncoated glass slides results in protein degradation; that protease and phosphatase inhibitors do not result in detectable improvement in number of peptides or semi tryptic peptides; and that digestion time longer than four hours drastically reduces the number of missed cleavages, but also increases the number of unexpectedly modified peptides. Overalkylation was the most dominant side reaction, which significantly increased overnight (P=0.05). The latter effect could almost completely be reverted by the use of a quenching agent (P=0.001). Taken together, our results show that it is of importance to carefully control sample handling steps so that reliable protein identification and quantitation can be performed within comparative proteomics studies using LCM. This article is part of a Special Issue entitled: Proteomics: The clinical link. PMID- 22296677 TI - Genetic susceptibility to invasive meningococcal disease: MBL2 structural polymorphisms revisited in a large case-control study and a systematic review. AB - Invasive infection caused by Neisseria meningitidis is a worldwide public health problem. Previous reports have indicated that carriage of common 'defective' structural polymorphisms of the host mannose-binding lectin gene (MBL2) greatly increases an individual's risk of developing the disease. We report the largest case-control study so far to investigate the effect of these polymorphisms in meningococcal disease (296 PCR-positive cases and 5196 population controls, all of European ancestry) and demonstrate that no change in risk is associated with the polymorphisms overall or in any age-defined subgroup. This finding contrasts with two smaller studies that reported an increase in risk. A systematic review of all studies of MBL2 polymorphisms in people of European ancestry published since 1999, including 24,693 individuals, revealed a population frequency of the combined 'defective'MBL2 allele of 0.230 (95% confidence limits: 0.226-0.234). The past reported associations of increased risk of meningococcal disease were because of low 'defective' allele frequencies in their study control populations (0.13 and 0.04) that indicate systematic problems with the studies. The data from our study and all other available evidence indicate that MBL2 structural polymorphisms do not predispose children or adults to invasive meningococcal disease. PMID- 22296678 TI - Endovascular intervention for acute stroke due to infective endocarditis: case report. AB - The overall incidence of neurological complications due to infective endocarditis is as high as 40%, with embolic infarcts more common than hemorrhagic strokes. The standard of care for typical strokes does not apply to infective endocarditis because there is a substantial risk of hemorrhage with thrombolysis. In the last decade there have been multiple case reports of intravenous and intraarterial thrombolysis with successful outcomes for acute strokes with related infective endocarditis, but successful endovascular interventions for acute strokes associated with infective endocarditis are rarely reported. To the authors' knowledge, this report is the first case in the literature to use a mechanical retrieval device in successful vegetation retrieval in an infective endocarditis acute stroke. Although an interventional approach for treatment of acute stroke related to infective endocarditis is a promising option, it is controversial and a cautious clinical decision should be made on a case-by-case basis. The authors conclude that this approach can be tested in a case series with matched controls, because this condition is rare and a randomized clinical trial is not a realistic option. PMID- 22296679 TI - Validation of frontal near-infrared spectroscopy as noninvasive bedside monitoring for regional cerebral blood flow in brain-injured patients. AB - OBJECT: Near-infrared spectroscopy (NIRS) offers noninvasive bedside measurement of direct regional cerebral arteriovenous (mixed) brain oxygenation. To validate the accuracy of this monitoring technique, the authors analyzed the statistical correlation of NIRS and CT perfusion with respect to regional cerebral blood flow (CBF) measurements. METHODS: The authors retrospectively reviewed all cases in which NIRS measurements were obtained at a single, academic neurointensive care unit from February 2008 to June 2011 in which CT perfusion was performed at the same time as NIRS data was collected. Regions of interest were obtained 2.5 cm below the NIRS bifrontal scalp probe on CT perfusion with an average volume between 2 and 4 ml, with mean CBF values used for purposes of analysis. Linear regression analysis was performed for NIRS and CBF values. RESULTS: The study included 8 patients (2 men, 6 women), 6 of whom suffered subarachnoid hemorrhage, 1 ischemic stroke, and 1 intracerebral hemorrhage and brain edema. Mean CBF measured by CT perfusion was 61 ml/100 g/min for the left side and 60 ml/100 g/min for the right side, while mean NIRS values were 75 on the right and 74 on the left. Linear regression analysis demonstrated a statistically significant probability value (p<0.0001) comparing NIRS frontal oximetry and CT perfusion obtained CBF values. CONCLUSIONS: The authors demonstrated a linear correlation for frontal NIRS cerebral oxygenation measurements compared with regional CBF on CT perfusion imaging. Thus, frontal NIRS cerebral oxygenation measurement may serve as a useful, noninvasive, bedside intensive care unit monitoring tool to assess brain oxygenation in a direct manner. PMID- 22296680 TI - Cerebral blood flow. PMID- 22296681 TI - Is the poly A (T>C) mutation a causative factor for misdiagnosis in second trimester prenatal diagnosis of beta-thalassemia by fetal blood analysis on high performance liquid chromatography? AB - We report the problems in diagnosis faced by two families referred for prenatal diagnosis of thalassemia where cordocentesis and fetal blood analysis by high performance liquid chromatography (HPLC) had to be done. The Hb A levels of the fetal blood measured by HPLC on the VARIANTTM Hemoglobin Testing System were 1.2 and 6.7%, respectively, suggestive of a heterozygous beta-thalassemia (beta-thal) fetus in the first case and a normal fetus in the second case. In one family, one of the parents had a borderline Hb A(2) level and in the other, one parent had normal RBC indices. However, DNA sequencing, done later, showed that in the first case the fetus was a compound heterozygote for the IVS-I-5 (G>C) and the polyadenylation signal site [poly A (T>C)] mutation, while in the second case, the fetus was homozygous for the poly A mutation. This emphasizes that characterization of beta-thal mutations must be done whenever one of the parents has a borderline Hb A(2) level or normal RBC indices, and one should not rely on fetal blood analysis by HPLC for prenatal diagnosis of beta-thal so as to avoid misdiagnosis. PMID- 22296682 TI - Proteins and carbohydrates in nipple aspirate fluid predict the presence of atypia and cancer in women requiring diagnostic breast biopsy. AB - BACKGROUND: Herein we present the results of two related investigations. The first study determined if concentrations in breast nipple discharge (ND) of two proteins (urinary plasminogen activator, uPA and its inhibitor, PAI-1) predicted the presence of breast atypia and cancer in pre- and/or postmenopausal women requiring surgery because of a suspicious breast lesion. The second study assessed if these proteins increased the predictive ability of a carbohydrate (Thomsen Friedenreich, TF) which we previously demonstrated predicted the presence of disease in postmenopausal women requiring surgery. METHODS: In the first study we prospectively enrolled 79 participants from whom we collected ND, measured uPA and PAI-1 and correlated expression with pathologic findings. In the second study we analyzed 35 (uPA and PAI-1 in 24, uPA in an additional 11) ND samples collected from different participants requiring breast surgery, all of whom also had TF results. RESULTS: uPA expression was higher in pre- and PAI-1 in postmenopausal women with 1) cancer (DCIS or invasive) vs. either no cancer (atypia or benign pathology, p = .018 and .025, respectively), or benign pathology (p = .017 and .033, respectively); and 2) abnormal (atypia or cancer) versus benign pathology (p = .018 and .052, respectively). High uPA and PAI-1 concentrations and age were independent predictors of disease in premenopausal women, with an area under the curve (AUC) of 83-87% when comparing diseased vs. benign pathology. uPA, TF, and age correctly classified 35 pre- and postmenopausal women as having disease or not 84-91% of the time, whereas combining uPA+PAI-1+TF correctly classified 24 women 97-100% of the time. CONCLUSIONS: uPA and PAI-1 concentrations in ND were higher in women with atypia and cancer compared to women with benign disease. Combining uPA, PAI-1 and TF in the assessment of women requiring diagnostic breast surgery maximized disease prediction. The assessment of these markers may prove useful in early breast cancer detection. PMID- 22296683 TI - D-Lactate altered mitochondrial energy production in rat brain and heart but not liver. AB - BACKGROUND: Substantially elevated blood D-lactate (DLA) concentrations are associated with neurocardiac toxicity in humans and animals. The neurological symptoms are similar to inherited or acquired abnormalities of pyruvate metabolism. We hypothesized that DLA interferes with mitochondrial utilization of L-lactate and pyruvate in brain and heart. METHODS: Respiration rates in rat brain, heart and liver mitochondria were measured using DLA, LLA and pyruvate independently and in combination. RESULTS: In brain mitochondria, state 3 respiration was 53% and 75% lower with DLA as substrate when compared with LLA and pyruvate, respectively (p < 0.05). Similarly in heart mitochondria, state 3 respiration was 39% and 86% lower with DLA as substrate when compared with LLA or pyruvate, respectively (p < 0.05). However, state 3 respiration rates were similar between DLA, LLA and pyruvate in liver mitochondria. Combined incubation of DLA with LLA or pyruvate markedly impaired state 3 respiration rates in brain and heart mitochondria (p < 0.05) but not in liver mitochondria. DLA dehydrogenase activities were 61% and 51% lower in brain and heart mitochondria compared to liver, respectively, whereas LLA dehydrogenase activities were similar across all three tissues. An LDH inhibitor blocked state 3 respiration with LLA as substrate in all three tissues. A monocarboxylate transporter inhibitor blocked respiration with all three substrates. CONCLUSIONS: DLA was a poor respiratory substrate in brain and heart mitochondria and inhibited LLA and pyruvate usage in these tissues. Further studies are warranted to evaluate whether these findings support, in part, the possible neurological and cardiac toxicity caused by high DLA levels. PMID- 22296684 TI - The substance view: a critique. AB - According to the theory of intrinsic value and moral standing called the 'substance view,' what makes it prima facie seriously wrong to kill adult human beings, human infants, and even human fetuses is the possession of the essential property of the basic capacity for rational moral agency - a capacity for rational moral agency in root form and thereby not remotely exercisable. In this critique, I cover three distinct reductio charges directed at the substance view's conclusion that human fetuses have the same intrinsic value and moral standing as adult human beings. After giving consideration to defenders of the substance view's replies to these charges, I then critique each of them, ultimately concluding that none is successful. Of course, in order to understand all of these things - the reductio charges, defenders of the substance view's replies to them, and my criticisms of their replies - one must have a better understanding of the substance view (in particular, its understanding of rational moral agency) as well as its defense. Accordingly, I address the substance view's understanding of rational moral agency as well as present its defense. PMID- 22296685 TI - Halophilanema prolata n. gen., n. sp. (Nematoda: Allantonematidae), a parasite of the intertidal bug, Saldula laticollis (Reuter)(Hemiptera: Saldidae) on the Oregon coast. AB - BACKGROUND: It is rare to find terrestrial nematode lineages parasitizing arthropods inhabiting the intertidal or littoral zone of the oceans. During an ecological study along the Oregon dunes, an allantonematid nematode (Tylenchomorpha: Allantonematidae) was discovered parasitizing the intertidal shore bug, Saldula laticollis (Reuter)(Hemiptera: Saldidae). This shore bug is adapted to an intertidal environment and can survive short periods of submergence during high tides. The present study describes the nematode parasite and discusses aspects of its development, ecology and evolution. METHODS: Adults and last instar nymphs of S. laticollis (Hemiptera: Saldidae) were collected from the high intertidal zone among clumps of Juncus L. (Juncaceae) plants at Waldport, Oregon on October 3, 2011. The bugs were dissected in 1% saline solution and the nematodes killed in 1% Ringers solution and immediately fixed in 5% formalin (at 20 degrees C). Third stage juveniles removed from infected hosts were maintained in 1% saline solution until they matured to the adult stage, molted and mated. RESULTS: Halophilanema prolata n. gen., n. sp. (Nematoda: Allantonematidae) is described from last instar nymphs and adults of the intertidal bug, Saldula laticollis on the Oregon coast. The new genus can be distinguished from other genera in the Allantonematidae by a stylet lacking basal knobs in both sexes, an excretory pore located behind the nerve ring, ribbed spicules, a gubernaculum, the absence of a bursa and the elongate-tubular shape of the ovoviviparous parasitic females. Studies of the organogenesis of Halophilanema showed development to third stage juveniles in the uterus of parasitic females. Maturation to the free-living adults and mating occurred in the environment. The incidence of infection of S. laticollis ranged from 0% to 85% depending on the microhabitat in the intertidal zone. CONCLUSIONS: Based on the habitat and morphological characters, it is proposed that Halophilanema adapted a parasitic existence fairly recently, evolutionarily speaking. It was probably a free-living intertidal or shore nematode that fed on microorganisms, especially fungi, in the intertidal habitat and became parasitic after saldids entered the environment. Halophilanema represents the first described nematode parasite of an intertidal insect. PMID- 22296686 TI - Synchrotron X-ray, photoluminescence, and quantum chemistry studies of bismuth embedded dehydrated zeolite Y. AB - For the first time, direct experimental evidence of the formation of monovalent Bi (i.e., Bi(+)) in zeolite Y is provided based on the analysis of high resolution synchrotron powder X-ray diffraction data. Photoluminescence results as well as quantum chemistry calculations suggest that the substructures of Bi(+) in the sodalite cages contribute to the ultrabroad near-infrared emission. These results not only enrich the well-established spectrum of optically active zeolites and deepen the understanding of bismuth related photophysical behaviors, but also may raise new possibilities for the design and synthesis of novel hybrid nanoporous photonic materials activated by other heavier p-block elements. PMID- 22296687 TI - The use of darbepoetin to stimulate erythropoiesis in anemia of chronic kidney disease in cats: 25 cases. AB - BACKGROUND: Anemia is present in 30-65% in cats with chronic kidney disease (CKD) and few long-term treatment options exist. Darbepoetin is effective in treating anemia of kidney disease in humans and may be used in cats. HYPOTHESIS/OBJECTIVE: To evaluate the use of darbepoetin, a recombinant analog of human erythropoietin, to stimulate erythropoiesis, and to effectively treat anemia of kidney disease in cats. ANIMALS: Twenty-five of 66 cats that received >= 2 doses of darbepoetin at the Animal Medical Center between January 2005 and December 2009 were included in this study. METHODS: Cats were included in the study if they received darbepoetin and follow-up data were available for at least 56 days and had CKD as a primary clinical diagnosis. Cats were excluded if they were treated with darbepoetin but did not have kidney disease. Response to treatment was defined as reaching or exceeding a target packed red blood cell volume or hematocrit of 25%. RESULTS: Fourteen of 25 cats responded. Thirteen of those 14 cats received a dosage of 1 MUg/kg/wk or higher. Presumptive adverse effects included vomiting, hypertension, seizures, and fever. CONCLUSIONS AND CLINICAL RELEVANCE: Darbepoetin is effective for treatment of anemia of kidney disease in cats. Pure red cell aplasia appears to be less common with darbepoetin than with epoetin usage. PMID- 22296688 TI - "John Grippo: a modern day pioneer". PMID- 22296689 TI - Computer-aided design/computer-aided manufacturing technology in customized orthodontic appliances. PMID- 22296690 TI - Abfraction, abrasion, biocorrosion, and the enigma of noncarious cervical lesions: a 20-year perspective. AB - Hitherto, noncarious cervical lesions (NCCLs) of teeth have been generally ascribed to either toothbrush-dentifrice abrasion or acid "erosion." The last two decades have provided a plethora of new studies concerning such lesions. The most significant studies are reviewed and integrated into a practical approach to the understanding and designation of these lesions. A paradigm shift is suggested regarding use of the term "biocorrosion" to supplant "erosion" as it continues to be misused in the United States and many other countries of the world. Biocorrosion embraces the chemical, biochemical, and electrochemical degradation of tooth substance caused by endogenous and exogenous acids, proteolytic agents, as well as the piezoelectric effects only on dentin. Abfraction, representing the microstructural loss of tooth substance in areas of stress concentration, should not be used to designate all NCCLs because these lesions are commonly multifactorial in origin. Appropriate designation of a particular NCCL depends upon the interplay of the specific combination of three major mechanisms: stress, friction, and biocorrosion, unique to that individual case. Modifying factors, such as saliva, tongue action, and tooth form, composition, microstructure, mobility, and positional prominence are elucidated. CLINICAL SIGNIFICANCE: By performing a comprehensive medical and dental history, using precise terms and concepts, and utilizing the Revised Schema of Pathodynamic Mechanisms, the dentist may successfully identify and treat the etiology of root surface lesions. Preventive measures may be instituted if the causative factors are detected and their modifying factors are considered. PMID- 22296691 TI - Commentary. Abfraction, abrasion, biocorrosion, and the enigma of noncarious cervical lesions: a 20-year perspective. PMID- 22296692 TI - Management of provisional restorations' deficiencies: a literature review. AB - Provisional restorations are designed in order to protect oral structures and promote function and esthetics for a limited period of time, after which they are to be replaced by a definite prosthesis. They play a particular role in diagnostic procedures and continued evaluation of the treatment plan, as they should resemble the form and function of the definite rehabilitation that they precede. Therefore, interim treatment should satisfy the criteria of marginal adaptation, strength, and longevity. In complicated treatment plans that intend to last for extended periods of time, the function of provisional prostheses involves the possibility of relining, modification, or repair. These adjustments raise considerations regarding the strength of the resultant bond. Chemical composition of the base and repair material, surface characteristics of fracture parts, and time elapsed since the initial set of the rehabilitation should be considered in the decision of the appropriate repair material and technique. Proper pretreatment of the provisional components' surfaces is essential to ensure bonding as well. The purpose of this article is to illustrate the management of provisional restorations' deficiencies. This article highlights possible failures of custom-fabricated provisional restorations, describes methods to prevent their occurrence, and discusses clinical techniques for their management. Finally, the proper combination of materials and surface preparation to achieve the optimum treatment outcomes are presented. CLINICAL SIGNIFICANCE: Provisional restorations' failures and other deficiencies are encountered by clinicians on a daily basis. Adequate laboratory techniques and material combinations presented herein may contribute to their efficient and predictable modifications and repairs. PMID- 22296693 TI - Commentary. Management of provisional restorations' deficiencies: a literature review. PMID- 22296694 TI - Practitioner and patient perceptions of orthodontic treatment: is the patient always right? AB - PURPOSE: As dentists embrace evidence-based clinical practice, we place increased emphasis on patient values. Standards like Angle Classification are not related to patient perceptions of the tangible benefits of treatment. This study quantifies the differences dentists and patients perceive in orthodontic treatment outcome. MATERIALS AND METHODS: A survey is used to quantify a patient's perception of orthodontic treatment. It was completed by 30 patients who completed treatment at the University of Pittsburgh School of Dental Medicine. Their responses were compared with the perceptions of five orthodontists, three general dentists, and two prosthodontists. RESULTS: Multivariate analysis of variance found the differences between and within the subjects to be significant at p < 0.004. Univariate analysis of variance of the initial scores showed the data to be significant at p < 0.002 and pairwise comparisons showed significant mean differences. Final score analysis of variance was significant at p < 0.001 and pairwise comparison showed significant mean differences. CONCLUSIONS: Patients and general dentists have a significantly less favorable initial perception of their dental esthetics and function when compared with orthodontists. Final scores of esthetic and functional perceptions between the patients and all three dentist groups showed significant differences, with patients perceiving the results of their treatment more favorably than practitioners. CLINICAL SIGNIFICANCE: The data herein elucidates differences in the value systems of professionals and patients. It is meant to encourage dentists to consider whether these differences justify the persistence of traditional orthodontic treatment goals or if treatment planning should incorporate consideration of each individual patient's preferences to maximize utility. PMID- 22296695 TI - Commentary. Practitioner and patient perceptions of orthodontic treatment: is the patient always right? PMID- 22296696 TI - Translucency of value resin composites used to replace enamel in stratified composite restoration techniques. AB - BACKGROUND: The translucency of enamel shade is a crucial property that affects the color of a layered restoration. OBJECTIVE: This study evaluated the translucency of high-, medium-, and low-value resin composites (4 Seasons, Ivoclar Vivadent, Schaan, Liechtenstein) used to replace enamel in stratified composite restoration techniques. MATERIALS AND METHODS: The color specimens with 12 mm in diameter and various thicknesses (0.5, 1.0, 1.5, 2.0, 3.0, 4.0 mm) were measured after polymerization on a reflection spectrophotometer over white and black backgrounds to calculate the translucency parameter (TP). The statistical analysis of TP was accomplished using two-way analysis of variance (p < 0.05). Significant differences were revealed by the Tukey's Honestly Significant Difference post hoc test. RESULTS: Translucency of the value composite resins was influenced by the value and thickness. Color of value resin composites was dependent on the background contrast at the evaluated thicknesses. CONCLUSIONS: High-value composite resins were more translucent than medium-value composites, which were more translucent than low-value composites. The translucency decreased as the thickness of the specimens increased. CLINICAL SIGNIFICANCE: The results suggest that special attention should be paid to the thickness of the increment of value composite resins when reproducing translucency of natural tooth enamel. PMID- 22296697 TI - Commentary. Translucency of value resin composites used to replace enamel in stratified composite restoration techniques. PMID- 22296698 TI - A case series: herpes simplex virus as an occupational hazard. AB - STATEMENT OF THE PROBLEM: Herpes labialis infections are common and present a serious risk to the dental team. PURPOSE OF THE STUDY: The purpose is to make dentists aware of the risks involved with treatment of patients with active herpes labialis. In addition, evidence-based risk-management strategies are presented. METHODS AND MATERIALS: The incidence and natural history of herpes simplex virus type 1 (HSV-1) are reviewed. Four previously unreported case histories are presented to illustrate the impact common sequelae of HSV-1 can have on the dental team. The differences between HSV-1 and the blood-borne diseases which are the focus of universal precautions are discussed. In particular, the highly contagious, highly transmissible nature of HSV-1 and its transmission through aerosols are highlighted. Finally, the need to include protection against aerosols in the profession's understanding of universal precautions is noted. RESULTS: The authors suggest limiting the treatment of patients with active lesions to urgent care only, and treating active HSV-1 lesions to reduce time of healing. For four common clinical situations involving HSV-1 infections, evidence-based methods for protecting the dental team and the patient from cross-contamination are also presented. CONCLUSION: While it is clear that the treatment of patients with active herpes labialis lesions increases risk of cross-infection, there are good protocols for controlling this risk. CLINICAL SIGNIFICANCE: By bringing common vectors of cross-infection to light and providing evidence-based protocols for preventing them, this article provides practitioners with positive steps that can be taken for controlling the risk of spreading herpes infections to the dental team. PMID- 22296699 TI - Commentary. A Case Series: herpes simplex virus as an occupational hazard. PMID- 22296701 TI - Mislocalization of the exitatory amino-acid transporters (EAATs) in human astrocytoma and non-astrocytoma cancer cells: effect of the cell confluence. AB - BACKGROUND: Astrocytomas are cancers of the brain in which high levels of extracellular glutamate plays a critical role in tumor growth and resistance to conventional treatments. This is due for part to a decrease in the activity of the glutamate transporters, i.e. the Excitatory Amino Acid Transporters or EAATs, in relation to their nuclear mislocalization in astrocytoma cells. Although non astrocytoma cancers express EAATs, the localization of EAATs and the handling of L-glutamate in that case have not been investigated. METHODS: We looked at the cellular localization and activity of EAATs in human astrocytoma and non astrocytoma cancer cells by immunofluorescence, cell fractionation and L glutamate transport studies. RESULTS: We demonstrated that the nuclear mislocalization of EAATs was not restricted to astrocytoma and happened in all sub-confluent non-astrocytoma cancer cells we tested. In addition, we found that cell-cell contact caused the relocalization of EAATs from the nuclei to the plasma membrane in all human cancer cells tested, except astrocytoma. CONCLUSIONS: Taken together, our results demonstrated that the mislocalization of the EAATs and its associated altered handling of glutamate are not restricted to astrocytomas but were also found in human non-astrocytoma cancers. Importantly, we found that a cell contact-dependent signal caused the relocalization of EAATs at the plasma membrane at least in human non-astrocytoma cancer cells, resulting in the correction of the altered transport of glutamate in such cancer cells but not in astrocytoma. PMID- 22296702 TI - Novel echocardiographic techniques to assess left atrial size, anatomy and function. AB - Three-dimensional echocardiography (3DE) and speckle tracking echocardiography (STE) have recently applied as imaging techniques to accurately evaluate left atrial (LA) size, anatomy and function. 3DE and off-line quantification softwares, have allowed, in comparison to magnetic resonance imaging, the most time-efficient and accurate method of LA volume quantification. STE provides a non-Doppler, angle-independent and objective quantification of LA myocardial deformation. Data regarding feasibility, accuracy and clinical applications of LA analysis by 3DE and STE are rapidly gathering. This review describes the fundamental concepts of LA 3DE and STE, illustrates how to obtain respective measurements and discuss their recognized and emerging clinical applications. PMID- 22296704 TI - Serum levels of 25-hydroxyvitamin D, oral health and chronic obstructive pulmonary disease. AB - AIM: To evaluate the associations of serum 25-Hydroxyvitamin D [25(OH)D] levels with periodontal health and chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS: We conducted a case-control study of 193 COPD patients and 181 controls. Their periodontal status and lung function were examined, and serum 25(OH)D levels were measured. RESULTS: Mean serum 25(OH)D concentrations were significantly lower in the COPD group than in the controls (32.1 versus 35.8 nmol/l; p = 0.002). Serum 25(OH)D concentrations were positively correlated with lung function among non-smokers and negatively correlated with plaque index (PLI) among former smokers. After adjustment for age, gender, body mass index, season and smoking status, periodontal indexes were significantly associated with serum 25(OH)D concentrations (number of remaining teeth among all groups; probing depth, clinical attachment level, bleeding index, PLI and alveolar bone loss among COPD group). Lower serum 25(OH)D concentrations were significantly associated with an increased risk of COPD among former smokers (Odd ratio 4.11; 95% confidence interval 1.47-11.5; p = 0.007) after adjustment for periodontal indexes and other variables. CONCLUSIONS: Lower serum 25(OH)D concentrations were significantly associated with poor periodontal health and an increased risk of COPD. PMID- 22296705 TI - Developmental outcome of very low birth weight infants in a developing country. AB - BACKGROUND: Advances in neonatal care allow survival of extremely premature infants, who are at risk of handicap. Neurodevelopmental follow up of these infants is an essential part of ongoing evaluation of neonatal care. The neonatal care in resource limited developing countries is very different to that in first world settings. Follow up data from developing countries is essential; it is not appropriate to extrapolate data from units in developed countries. This study provides follow up data on a population of very low birth weight (VLBW) infants in Johannesburg, South Africa. METHODS: The study sample included all VLBW infants born between 01/06/2006 and 28/02/2007 and discharged from the neonatal unit at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Bayley Scales of Infant and Toddler Development Version 111 (BSID) 111 were done to assess development. Regression analysis was done to determine factors associated with poor outcome. RESULTS: 178 infants were discharged, 26 were not available for follow up, 9 of the remaining 152 (5.9%) died before an assessment was done; 106 of the remaining 143 (74.1%) had a BSID 111 assessment. These 106 patients form the study sample; mean birth weight and mean gestational age was 1182 grams (SD: 197.78) and 30.81 weeks (SD: 2.67) respectively. The BSID (111) was done at a median age of 16.48 months. The mean cognitive subscale was 88.6 (95% CI: 85.69 91.59), 9 (8.5%) were < 70, mean language subscale was 87.71 (95% CI: 84.85 90.56), 10 (9.4%) < 70, and mean motor subscale was 90.05 (95% CI: 87.0-93.11), 8 (7.6%) < 70. Approximately one third of infants were identified as being at risk (score between 70 and 85) on each subscale. Cerebral palsy was diagnosed in 4 (3.7%) of babies. Factors associated with poor outcome included cystic periventricular leukomalacia (PVL), resuscitation at birth, maternal parity, prolonged hospitalisation and duration of supplemental oxygen. PVL was associated with poor outcome on all three subscales. Birth weight and gestational age were not predictive of neurodevelopmental outcome. CONCLUSION: Although the neurodevelopmental outcome of this group of VLBW infants was within the normal range, with a low incidence of cerebral palsy, these results may reflect the low survival of babies with a birth weight below 900 grams. In addition, mean subscale scores were low and one third of the babies were identified as "at risk", indicating that this group of babies warrants long-term follow up into school going age. PMID- 22296706 TI - Amorphous silica nanoparticles size-dependently aggravate atopic dermatitis-like skin lesions following an intradermal injection. AB - BACKGROUND: Due to the rising use of nanomaterials (NMs), there is concern that NMs induce undesirable biological effects because of their unique physicochemical properties. Recently, we reported that amorphous silica nanoparticles (nSPs), which are one of the most widely used NMs, can penetrate the skin barrier and induce various biological effects, including an immune-modulating effect. Thus, it should be clarified whether nSPs can be a risk factor for the aggravation of skin immune diseases. Thus, in this study, we investigated the relationship between the size of SPs and adjuvant activity using a model for atopic dermatitis. RESULTS: We investigated the effects of nSPs on the AD induced by intradermaly injected-mite antigen Dermatophagoides pteronyssinus (Dp) in NC/Nga mice. Ear thickness measurements and histopathological analysis revealed that a combined injection of amorphous silica particles (SPs) and Dp induced aggravation of AD in an SP size-dependent manner compared to that of Dp alone. In particular, aggravation was observed remarkably in nSP-injected groups. Furthermore, these effects were correlated with the excessive induction of total IgE and a stronger systemic Th2 response. We demonstrated that these results are associated with the induction of IL-18 and thymic stromal lymphopoietin (TSLP) in the skin lesions. CONCLUSIONS: A particle size reduction in silica particles enhanced IL-18 and TSLP production, which leads to systemic Th2 response and aggravation of AD-like skin lesions as induced by Dp antigen treatment. We believe that appropriate regulation of nanoparticle physicochemical properties, including sizes, is a critical determinant for the design of safer forms of NMs. PMID- 22296707 TI - Enhancing ethylbenzene vapors degradation in a hybrid system based on photocatalytic oxidation UV/TiO2-In and a biofiltration process. AB - The use of hybrid processes for the continuous degradation of ethylbenzene (EB) vapors has been evaluated. The hybrid system consists of an UV/TiO(2)-In photooxidation coupled with a biofiltration process. Both the photocatalytic system using P25-Degussa or indium-doped TiO(2) catalysts and the photolytic process were performed at UV-wavelengths of 254 nm and 365 nm. The experiments were carried out in an annular plug flow photoreactor packed with granular perlite previously impregnated with the catalysts, and in a glass biofilter packed with perlite and inoculated with a microbial consortium. Both reactors were operated at an inlet loading rate of 127 g m(-3)h(-1). The greatest degradation rate of EB (0.414 ng m(-2)min(-1)) was obtained with the TiO(2)-In 1%/365 nm photocatalytic system. The elimination capacity (EC) obtained in the control biofilter had values ~ 60 g m(-3)h(-1). Consequently, the coupled system was operated for 15 days, and a maximal EC of 275 g m(-3)h(-1). Thus, the results indicate that the use of hybrid processes enhanced the EB vapor degradation and that this could be a promising technology for the abatement of recalcitrant volatile organic compounds. PMID- 22296708 TI - Application of photochemical technologies for treatment of landfill leachate. AB - Because of widely varying practices in solid waste management, an all-inclusive solution to long-term management of landfill leachate is currently not available. There is a major technological need for sustainable, economical options for safe discharge of leachate to the environment. Two potential on-site pretreatment technologies, photochemical iron-mediated aeration (PIMA) and TiO(2) photocatalysis were compared for treatment of landfill leachate at laboratory scale. Results of bench scale testing of real landfill leachate with PIMA and TiO(2) photocatalysis showed up to 86% conversion of refractory COD to complete mineralization, up to 91% removal of lead, up to 71% removal of ammonia without pH adjustment, and up to 90% effective color removal with detention times between 4 and 6h, in field samples. The estimated contact times for 90% removal of COD, ammonia, lead, and color were found to be on the order of 10-200 h for PIMA and 3 37 h for TiO(2) photocatalysis. Testing with actual leachate samples showed 85% TiO(2) photocatalyst recovery efficiency with no loss in performance after multiple (n>4 uses). Pre-filtration was not found to be necessary for effective treatment using either process. PMID- 22296709 TI - The influence of titanate nanotube on the improved thermal properties and the smoke suppression in poly(methyl methacrylate). AB - The well-dispersed poly(methyl methacrylate)/titanate nanotube (PMMA/TNT) composites were synthesized by in situ polymerization of methyl methacrylate (MMA) in ethanol solution. Thermal stability and the glass transition temperature of the composites are significantly enhanced with a proper amount of TNTs. The comparison between PMMA/TNTs and PMMA/TiO(2) composites suggests the formation of network in PMMA/TNTs composite. The coaction of dehydration and the network is believed to be the crucial factor which improves the thermal properties. TG-FTIR analysis shows that the amount of organic volatiles of PMMA is significantly reduced and the non-flammable CO(2) is generated after incorporating TNTs. It implies the reduced toxicity of the volatiles. The possible mechanism of the smoke suppression is proposed as the dehydration and adsorption effect of TNTs. PMID- 22296710 TI - An optimized procedure for preconcentration, determination and on-line recovery of palladium using highly selective diphenyldiketone-monothiosemicarbazone modified silica gel. AB - A novel, highly selective, efficient and reusable chelating resin, diphenyldiketone-monothiosemicarbazone modified silica gel, was prepared and applied for the on-line separation and preconcentration of Pd(II) ions in catalytic converter and spiked tap water samples. Several parameters like effect of pH, sample volume, flow rate, type of eluent, and influence of various ionic interferences, etc. were evaluated for effective adsorption of palladium at trace levels. The resin was found to be highly selective for Pd(II) ions in the pH range 4-5 with a very high sorption capacity of 0.73 mmol/g and preconcentration factor of 335. The present environment friendly procedure has also been applied for large-scale extraction by employing the use of newly designed reactor in which on-line separation and preconcentration of Pd can be carried out easily and efficiently in short duration of time. PMID- 22296711 TI - Successful primary angioplasty in patient with ST-segment elevation myocardial infarction caused by large septal branch occlusion. PMID- 22296712 TI - The impact of sexual or physical abuse history on pain-related outcomes among blacks and whites with chronic pain: gender influence. AB - OBJECTIVES: Physical and sexual abuses commonly co-occur with chronic pain. We hypothesized that: 1) abuse history questions would form distinct factors that relate differently to pain perceptions and pain outcomes; 2) abuse history consequences on physical and mental health differ by gender; and 3) different abuse types and age of occurrence (childhood vs adolescent/adulthood) predict different negative outcomes. METHODS: Chronic pain patients at a tertiary care pain center provided data (64% women, 50% black) through a confidential survey. Factors were formed for abuse type and age. Linear regression, controlling for socio-demographic information, was used to examine the relationship between abuse and abuse by sex interactions with pain-related outcomes. RESULTS: Six 3-item abuse factors (alpha = 0.77-0.91)-sexual molestation, sexual penetration, and physical abuse-were identified in both childhood and adulthood. Lifetime prevalence of abuse was 70% for men and 65% for women. Women experienced lower physical abuse (P = 0.01) in childhood, and higher penetration (P = 0.02) in adulthood. Decreased general health was associated with all abuse types (P < 0.05) in childhood. Affective pain was associated with all childhood abuse scales and adulthood molestation, though childhood molestation only for men (P = 0.04). Disability was associated with childhood (P = 0.02) and adulthood rape (P = 0.04). Men with childhood or adulthood molestation (P = 0.02; P = 0.02) reported higher post-traumatic stress disorder. CONCLUSIONS: Our study confirms physical and mental health, and pain-related outcomes are affected by abuse history for men and women. These results support screening all patients for abuse to improve the survivor's overall health and well-being. PMID- 22296713 TI - Hippocampal function is not required for the precision of remote place memory. AB - BACKGROUND: During permanent memory formation, recall of acquired place memories initially depends on the hippocampus and eventually become hippocampus independent with time. It has been suggested that the quality of original place memories also transforms from a precise form to a less precise form with similar time course. The question arises of whether the quality of original place memories is determined by brain regions on which the memory depends. RESULTS: To directly test this idea, we introduced a new procedure: a non-associative place recognition memory test in mice. Combined with genetic and pharmacological approaches, our analyses revealed that place memory is precisely maintained for 28 days, although the recall of place memory shifts from hippocampus-dependent to hippocampus-independent with time. Moreover, the inactivation of the hippocampal function does not inhibit the precision of remote place memory. CONCLUSION: These results indicate that the quality of place memories is not determined by brain regions on which the memory depends. PMID- 22296714 TI - [The human papillomavirus vaccine: is it of value in dermatology?]. PMID- 22296715 TI - Immunoproteasomes at the interface of innate and adaptive immune responses: two faces of one enzyme. AB - The immunoproteasome is a specific proteasome isoform induced by interferons. Its proteolytic function has been almost exclusively connected with the adaptive immune response and improved MHC class I antigen presentation. However, IFN signaling also exposes cells to oxidative stress with concomitant production of nascent-oxidant damaged poly-ubiquitylated proteins. Here we discuss how immunoproteasomes protect cells against accumulation of toxic protein-aggregates and how i-proteasomes dysfunction associates with different diseases. We propose that the immunoproteasome has a central function at the interface between the innate and adaptive immune response and that its predominant protective innate function determines its favorable role in the adaptive immune response. PMID- 22296716 TI - Differential processing of self-antigens by subsets of thymic stromal cells. AB - The stromal network of the thymus provides a unique environment that supports the development of mature CD4(+) and CD8(+) T cells expressing a very diverse repertoire of T cell receptors (TCR) with limited reactivity to self-antigens. Thymic cortical epithelial cells (cTECs) are specialized antigen-presenting cells (APCs) that promote the positive selection of developing thymocytes while medullary thymic epithelial cells (mTECs) and thymic dendritic cells (tDCs) induce central tolerance to self-antigens. Recent studies showed that cTECs express a unique set of proteases involved in the generation of self-peptides presented by major-histocompatibility encoded molecules (pMHC) and consequently may express a unique set of pMHC complexes. Conversely, the stromal cells of the medulla developed several mechanisms to mirror as closely as possible the constellation of self-peptides derived from peripheral tissues. Here, we discuss how these different features allow for the development of a highly diverse but poorly self-reactive repertoire of functional T cells. PMID- 22296717 TI - Temperature-dependent solid-state electron transport through bacteriorhodopsin: experimental evidence for multiple transport paths through proteins. AB - Electron transport (ETp) across bacteriorhodopsin (bR), a natural proton pump protein, in the solid state (dry) monolayer configuration, was studied as a function of temperature. Transport changes from thermally activated at T > 200 K to temperature independent at <130 K, similar to what we have observed earlier for BSA and apo-azurin. The relatively large activation energy and high temperature stability leads to conditions where bR transports remarkably high current densities above room temperature. Severing the chemical bond between the protein and the retinal polyene only slightly affected the main electron transport via bR. Another thermally activated transport path opens upon retinal oxime production, instead of or in addition to the natural retinal. Transport through either or both of these paths occurs on a background of a general temperature-independent transport. These results lead us to propose a generalized mechanism for ETp across proteins, in which tunneling and hopping coexist and dominate in different temperature regimes. PMID- 22296719 TI - Who adopts improved fuels and cookstoves? A systematic review. AB - BACKGROUND: The global focus on improved cookstoves (ICSs) and clean fuels has increased because of their potential for delivering triple dividends: household health, local environmental quality, and regional climate benefits. However, ICS and clean fuel dissemination programs have met with low rates of adoption. OBJECTIVES: We reviewed empirical studies on ICSs and fuel choice to describe the literature, examine determinants of fuel and stove choice, and identify knowledge gaps. METHODS: We conducted a systematic review of the literature on the adoption of ICSs or cleaner fuels by households in developing countries. Results are synthesized through a simple vote-counting meta-analysis. RESULTS: We identified 32 research studies that reported 146 separate regression analyses of ICS adoption (11 analyses) or fuel choice (135 analyses) from Asia (60%), Africa (27%), and Latin America (19%). Most studies apply multivariate regression methods to consider 7-13 determinants of choice. Income, education, and urban location were positively associated with adoption in most but not all studies. However, the influence of fuel availability and prices, household size and composition, and sex is unclear. Potentially important drivers such as credit, supply-chain strengthening, and social marketing have been ignored. CONCLUSIONS: Adoption studies of ICSs or clean energy are scarce, scattered, and of differential quality, even though global distribution programs are quickly expanding. Future research should examine an expanded set of contextual variables to improve implementation of stove programs that can realize the "win-win-win" of health, local environmental quality, and climate associated with these technologies. PMID- 22296718 TI - Tooth dentin defects reflect genetic disorders affecting bone mineralization. AB - Several genetic disorders affecting bone mineralization may manifest during dentin mineralization. Dentin and bone are similar in several aspects, especially pertaining to the composition of the extracellular matrix (ECM) which is secreted by well-differentiated odontoblasts and osteoblasts, respectively. However, unlike bone, dentin is not remodelled and is not involved in the regulation of calcium and phosphate metabolism. In contrast to bone, teeth are accessible tissues with the shedding of deciduous teeth and the extractions of premolars and third molars for orthodontic treatment. The feasibility of obtaining dentin makes this a good model to study biomineralization in physiological and pathological conditions. In this review, we focus on two genetic diseases that disrupt both bone and dentin mineralization. Hypophosphatemic rickets is related to abnormal secretory proteins involved in the ECM organization of both bone and dentin, as well as in the calcium and phosphate metabolism. Osteogenesis imperfecta affects proteins involved in the local organization of the ECM. In addition, dentin examination permits evaluation of the effects of the systemic treatment prescribed to hypophosphatemic patients during growth. In conclusion, dentin constitutes a valuable tool for better understanding of the pathological processes affecting biomineralization. PMID- 22296720 TI - Medicare part D information seeking: the role of recognition of need and patient activation. AB - BACKGROUND: In 2006, Medicare beneficiaries had the opportunity to choose from multiple newly available Medicare prescription drug plans (PDPs). Many beneficiaries reported difficulty in finding helpful information, whereas others reported they never looked for information. OBJECTIVES: This study examines antecedents of beneficiary information-seeking behaviors when learning about Medicare part D and choosing a PDP by using the Wilson Model of Information Behavior as a conceptual framework. METHODS: A cross-sectional analysis of 7008 Medicare beneficiaries from the 2004 to 2005 Medicare Current Beneficiary Surveys was used to predict whether a beneficiary sought Medicare part D information and the number of information sources used among those who sought information. A negative binomial hurdle model was used to estimate the determinants of these outcomes. Particular attention was given to the roles of information need and patient activation in predicting the outcomes. RESULTS: The results show that beneficiaries stating a need for information were more likely to seek information (odds ratio [OR]=2.02) and use multiple information sources (incidence rate ratio [IRR]=1.13). Beneficiaries with low patient activation were less likely to seek information (OR=0.97) and use multiple information sources (IRR=0.98). CONCLUSIONS: Information need and patient activation are antecedents of both the decision to seek Medicare part D information and how beneficiaries seek information. Interventions aimed at improving Medicare part D-related information seeking and decision making should focus on helping beneficiaries identify their need for information accurately and increasing their level of activation. PMID- 22296721 TI - Relationship between body composition, inflammation and lung function in overweight and obese asthma. AB - BACKGROUND: The obese-asthma phenotype is not well defined. The aim of this study was to examine both mechanical and inflammatory influences, by comparing lung function with body composition and airway inflammation in overweight and obese asthma. METHODS: Overweight and obese (BMI 28-40 kg/m(2)) adults with asthma (n = 44) completed lung function assessment and underwent full-body dual energy x-ray absorptiometry. Venous blood samples and induced sputum were analysed for inflammatory markers. RESULTS: In females, android and thoracic fat tissue and total body lean tissue were inversely correlated with expiratory reserve volume (ERV). Conversely in males, fat tissue was not correlated with lung function, however there was a positive association between android and thoracic lean tissue and ERV. Lower body (gynoid and leg) lean tissue was positively associated with sputum %neutrophils in females, while leptin was positively associated with android and thoracic fat tissue in males. CONCLUSIONS: This study suggests that both body composition and inflammation independently affect lung function, with distinct differences between males and females. Lean tissue exacerbates the obese asthma phenotype in females and the mechanism responsible for this finding warrants further investigation. PMID- 22296723 TI - [Klebsiella pneumoniae induced sternoclavicular osteomyelitis in a cirrhotic patient]. PMID- 22296724 TI - [Uveitis: diagnostic approach]. AB - A 32 year-old woman was referred from the Ophthalmology Department to rule out a possible systemic disease. Her only past medical history of relevance was a tuberculosis contact during childhood. She complained of floaters and progressive blurring of vision in both eyes for some months, as well as arthralgia and cough. Her visual acuity was 0.3 in the right eye and 0.4 in the left eye. Biomicroscopy showed bilateral anterior granulomatous uveitis (1+ cells). Funduscopy showed bilateral vitritis 3+, snow banking and peripheral phlebitis. Fluorescein angiography did not show central vasculitis, and optical coherence tomography showed bilateral cystoid macular oedema. Fundus autofluorescence was normal. How would you initially assess this patient in order to decide which systemic examination should be performed, bearing in mind the ophthalmological manifestations? PMID- 22296725 TI - Probing the effects of residues located outside the agonist binding site on drug receptor selectivity in the nicotinic receptor. AB - The nicotinic acetylcholine receptors (nAChRs) are a family of closely related but pharmacologically distinct neurotransmitter-gated ion channels. They are therapeutic targets for a wide range of neurological disorders, and a key issue in drug development is selective targeting among the more than 20 subtypes of nAChRs that are known. The present work evaluates a proposed hydrogen bonding interaction involving a residue known as the "loop B glycine" that distinguishes receptors that are highly responsive to ACh and nicotine from those that are much less so. We have performed structure-function studies on the loop B site, including unnatural amino acid mutagenesis, in three different nAChR subtypes and found that the correlation between agonist potency and this residue is strong. Low potency receptor subtypes have a glycine at this key site, and mutation to a residue with a side chain converts a low potency receptor to a high potency receptor. Innately high potency receptors have a lysine at the loop B site and show a decrease in potency for the reverse mutation (i.e., introducing a glycine). This residue lies outside of the agonist binding site, and studies of other residues at the agonist binding site show that the details of how changes at the loop B glycine site impact agonist potency vary for differing receptor subtypes. This suggests a model in which the loop B residue influences the global shape of the agonist binding site rather than modulating any specific interaction. PMID- 22296726 TI - Evaluation of antigen specific recognition and cell mediated cytotoxicity by a modified lysispot assay in a rat colon carcinoma model. AB - BACKGROUND: Antigen-specific CD8+ cytotoxic T lymphocytes represent potent effector cells of the adaptive immune response against viruses as well as tumours. Therefore assays capable at exploring the generation and function of cytotoxic T lymphocytes represent an important objective for both clinical and experimental settings. METHODS: Here we show a simple and reproducible assay for the evaluation of antigen-specific CD8+ cytotoxic T lymphocytes based on a LysiSpot technique for the simultaneous determination of antigen-specific IFN gamma production and assessment of tumor cytolysis. The assay was developed within an experimental model of colorectal carcinoma, induced by the colorectal tumor cell line DHD-K12 that induces tumors in BDIX rats and, in turn, elicits a tumor- specific immune response. RESULTS: Using DHD-K12 cells transfected to express Escherichia coli beta-galactosidase as target cells, and by the fine setting of spot colours detection, we have developed an in vitro assay that allows the recognition of cytotoxic T lymphocytes induced in BDIX rats as well as the assessment of anti-tumour cytotoxicity. The method highlighted that in the present experimental model the tumour antigen-specific immune response was bound to killing target cells in the proportion of 55%, while 45% of activated cells were not cytotoxic but released IFN-gamma. Moreover in this model by an ELISPOT assay we demonstrated the specific recognition of a nonapeptide epitope called CSH-275 constitutionally express in DHD-K12 cells. CONCLUSIONS: The assay proved to be highly sensitive and specific, detecting even low frequencies of cytotoxic/activated cells and providing the evaluation of cytokine-expressing T cells as well as the extent of cytotoxicity against the target cells as independent functions. This assay may represent an important tool to be adopted in experimental settings including the development of vaccines or immune therapeutic strategies. PMID- 22296727 TI - Up-regulation of platelet-activating factor synthases and its receptor in spinal cord contribute to development of neuropathic pain following peripheral nerve injury. AB - BACKGROUND: Platelet-activating factor (PAF; 1-alkyl-2-acetyl-sn-glycero-3 phosphocholine) is a lipid mediator derived from cell membrane. It has been reported that PAF is involved in various pathological conditions, such as spinal cord injury, multiple sclerosis, neuropathic pain and intrathecal administration of PAF leads to tactile allodynia. However, the expression of PAF synthases and its receptor in the spinal cord following peripheral nerve injury is unknown. METHODS: Using the rat spared nerve injury (SNI) model, we investigated the expression of PAF synthases (LPCAT1 and 2) and PAF receptor (PAFr) mRNAs in the spinal cord. Reverse transcription polymerase chain reaction (RT-PCR) and double labeling analysis of in situ hybridization histochemistry (ISHH) with immunohistochemistry (IHC) were employed for the analyses. Pain behaviors were also examined with PAFr antagonist (WEB2086). RESULTS: RT-PCR showed that LPCAT2 mRNA was increased in the ipsilateral spinal cord after injury, but not LPCAT1 mRNA. Double-labeling of ISHH with IHC revealed that LPCAT1 and 2 mRNAs were constitutively expressed by a subset of neurons, and LPCAT2 mRNA was increased in spinal microglia after nerve injury. RT-PCR showed that PAFr mRNA was dramatically increased in the ipsilateral spinal cord after nerve injury. Double labeling analysis of ISHH with IHC revealed that after injury PAFr mRNA was predominantly colocalized with microglia in the spinal cord. Continuous intrathecal administration of the PAFr antagonist suppressed mechanical allodynia following peripheral nerve injury. Delayed administration of a PAFr antagonist did not reverse the mechanical allodynia. CONCLUSIONS: Our data show the histological localization of PAF synthases and its receptor in the spinal cord following peripheral nerve injury, and suggest that PAF/PAFr signaling in the spinal cord acts in an autocrine or paracrine manner among the activated microglia and neurons, thus contributing to development of neuropathic pain. PMID- 22296728 TI - Evaluation of the analytical performances of the novel Beckman Coulter AU5800. AB - OBJECTIVES: To assess the analytical performance of Beckman Coulter AU5800. DESIGN AND METHODS: Imprecision, linearity and comparison studies were performed on 12 routine clinical chemistry tests. RESULTS: Imprecision was comprised between 0.4 and 3.0%. The linearity was excellent, with regression coefficients always >1.000. The correlation with analogous tests on Unicell DxC ranged from 0.894 and 1.000. The productivity was 4884 tests/h. CONCLUSIONS: We found optimal balance between performance and productivity for the AU5800. PMID- 22296729 TI - Age- and sex-specific reference intervals for blood copper, zinc, calcium, magnesium, iron, lead, and cadmium in infants and children. AB - OBJECTIVES: Reference intervals for clinically important elements in infants and children are rarely reported, despite their importance for accurate clinical decision-making. The exploration of such reference intervals is essential. DESIGN AND METHODS: Seven elements, including copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), iron (Fe), lead (Pb), and cadmium (Cd), were analyzed on BOHUI 5100 and 2100 analyzers using blood samples from 4044 healthy infants and children. RESULTS: Age- and sex-specific reference intervals were established for Cu, Zn, Ca, Mg, Fe, Pb, and Cd. CONCLUSIONS: Established reference intervals for Cu, Zn, Ca, Mg and Fe can provide important guidance for the reasonable supplementation of trace elements and other essential elements in infants and children. Reference intervals for Pb and Cd can play a role in the surveillance and diagnosis of environmental overexposure. PMID- 22296730 TI - Long-term effect of pulsed radiofrequency on chronic cervical radicular pain refractory to repeated transforaminal epidural steroid injections. AB - OBJECTIVE: The article aims to evaluate the long-term effectiveness and safety of pulsed radiofrequency (PRF) on the dorsal root ganglion (DRG) in patients with chronic cervical radicular pain refractory to repeated transforaminal epidural steroid injections (TFESIs). DESIGN: This is a prospective observational study. METHODS: We retrospectively reviewed data on 112 subjects who had received repeated TFESIs for cervical radicular pain. Twenty-nine of those 112 patients continued to complain of persistent cervical radicular pain, despite an average of three repeated TFESIs. Among 29 patients with sustained arm pain of over 4 on the numerical rating scale (NRS), a total of 21 patients were included prospectively. Those 21 patients underwent PRF on the symptomatic cervical DRG and were evaluated carefully for neurologic deficits and side effects. The clinical outcomes were measured via NRS for arm pain before treatment, and 1, 3, 6, and 12 months after treatment. Successful pain relief was defined as a 50% or more reduction in the NRS score as compared with the pretreatment score. After 12 months, patients' satisfaction levels with treatment were determined. RESULTS: Fourteen of the 21 patients (66.7%) after cervical PRF stimulation reported pain relief of 50% or more at the 3-month and 12-month follow-up periods, respectively. Fifteen of the 21 patients (71.4%) were satisfied with their outcome at 12 months' posttreatment. No serious adverse effects were observed. CONCLUSION: Application of PRF to the DRG appears to be an effective and relatively safe intervention technique for chronic cervical radicular pain refractory to repeated TFESIs. PMID- 22296731 TI - Optimizing early detection of avian influenza H5N1 in backyard and free-range poultry production systems in Thailand. AB - For infectious diseases such as highly pathogenic avian influenza caused by the H5N1 virus (A/H5N1 HP), early warning system is essential. Evaluating the sensitivity of surveillance is a necessary step in ensuring an efficient and sustainable system. Stochastic scenario tree modeling was used here to assess the sensitivity of the A/H5N1 HP surveillance system in backyard and free-grazing duck farms in Thailand. The whole surveillance system for disease detection was modeled with all components and the sensitivity of each component and of the overall system was estimated. Scenarios were tested according to selection of high-risk areas, inclusion of components and sampling procedure, were tested. Nationwide passive surveillance (SSC1) and risk-based clinical X-ray (SSC2) showed a similar sensitivity level, with a median sensitivity ratio of 0.96 (95% CI 0.40-15.00). They both provide higher sensitivity than the X-ray laboratory component (SSC3). With the current surveillance design, the sensitivity of detection of the overall surveillance system when the three components are implemented, was equal to 100% for a farm level prevalence of 0.05% and 82% (95% CI 71-89%) for a level of infection of 3 farms. Findings from this study illustrate the usefulness of scenario-tree modeling to document freedom from diseases in developing countries. PMID- 22296732 TI - Where are the food animal veterinarian shortage areas anyway? AB - In 2010 the United States implemented the Veterinary Medicine Loan Repayment Program (VMLRP) to address perceived regional shortages in certain veterinary occupations, including food animal practice. With county as the unit of analysis, this paper describes a pair of models to evaluate factors associated with being designated a private practice shortage area in 2010. One model is used to explain food animal veterinarian location choices so as to provide an objective evaluation of comparative shortage. The other model seeks to explain the counties chosen as shortage areas. Model results are then used to evaluate the program. On the whole the program appears to perform quite well. For several states, however, VMLRP shortage designations are inconsistent with the food animal veterinarian location model. Comparative shortage is generally more severe in states that have no VMLRP designated private practice shortage counties than in states that do. PMID- 22296733 TI - A qualitative approach to measure the effectiveness of active avian influenza virus surveillance with respect to its cost: a case study from Switzerland. AB - The aim of the project was to apply cost-effectiveness analysis to the economic appraisal of avian influenza virus (AIV) surveillance, using the implemented surveillance programme in Switzerland as a case study. First a qualitative risk assessment approach was used to assess the expected impact of surveillance on the transmission and spread of AIV. The effectiveness of surveillance was expressed as the difference in defined probabilities between a scenario with surveillance and a scenario without surveillance. The following probabilities were modelled (i) transmission of highly pathogenic AIV (HPAIV) from wild birds to poultry, (ii) mutation from low pathogenic AIV (LPAIV) into HPAIV in poultry, and (iii) transmission of HPAIV to other poultry holdings given a primary outbreak. The cost-effectiveness ratio was defined conventionally as the difference in surveillance costs (DeltaC) divided by the change in probability (DeltaP), the technical objective, on the presumption that surveillance diminishes the respective probabilities. However, results indicated that surveillance in both wild birds and poultry was not expected to change the probabilities of primary and secondary AIV outbreaks in Switzerland. The overall surveillance costs incurred were estimated at 31,000 ?/year, which, to be a rational investment of resources, must still reflect the value policy makers attribute to other benefits from having surveillance (e.g. peace of mind). The advantage of the approach adopted is that it is practical, transparent, and thus able to clarify for policy makers the key variables to be taken into account when evaluating the economic efficiency of resources invested in surveillance, prevention and intervention to exclude AIV. PMID- 22296734 TI - Examining host-microbial interactions through the lens of NOD: From plants to mammals. AB - Nod-like receptors (NLRs) for detecting microbial invaders are features of many plant and animal families. Although broadly similar in form and function, intimate co-evolutionary events with environmental microbes have shaped specific classes of NLRs in different types of hosts. Details of the roles of different NLRs in signaling cellular immune responses to invading microbes are only beginning to emerge. This review will discuss the current understanding of NLRs in plants, invertebrates, and mammals, with emphasis on their role in regulating NF-kappaB and inflammasome activity in mammals. PMID- 22296735 TI - Calcium/calmodulin dependent kinase II contributes to persistent central neuropathic pain following spinal cord injury. AB - Chronic central neuropathic pain after central nervous system injuries remains refractory to therapeutic interventions. A novel approach would be to target key intracellular signaling proteins that are known to contribute to continued activation by phosphorylation of kinases, transcription factors, and/or receptors that contribute to changes in membrane excitability. We demonstrate that one signaling kinase, calcium/calmodulin-dependent kinase II (CaMKII), is critical in maintaining aberrant dorsal horn neuron hyperexcitability in the neuropathic pain condition after spinal cord injury (SCI). After contusion SCI at spinal level T10, activated CaMKII (phosphorylated, pCaMKII) expression is significantly upregulated in the T7/8 spinal dorsal horn in neurons, but not glial cells, and in oligodendrocytes in the dorsal column in the same rats that displayed at-level mechanical allodynia. Furthermore, identified spinothalamic neurons demonstrated significant increases of pCaMKII after SCI compared to sham-treated control animals. However, neither astrocytes nor microglia showed pCaMKII expression in either sham-treated or SCI rats. To demonstrate causality, treatment of SCI rats with KN-93, which prevents CaMKII activation, significantly attenuated at-level mechanical allodynia and aberrant wide dynamic range neuronal activity evoked by brush, pressure, and pinch stimuli and a graded series of von Frey stimuli, respectively. Persistent CaMKII activation contributes to chronic central neuropathic pain by mechanisms that involve maintained hyperexcitability of wide dynamic range dorsal horn neurons. Furthermore, targeting key signaling proteins is a novel, useful therapeutic strategy for treating chronic central neuropathic pain. PMID- 22296736 TI - Anti-inflammation effects of hydrogen saline in LPS activated macrophages and carrageenan induced paw oedema. AB - BACKGROUND: Oxidative stress is thought to play an important role in the pathogenesis of inflammation. Recent studies have found that hydrogen gas has the effect of eliminating free radicals. Whether hydrogen saline (more convenient to be used than hydrogen gas) has the anti-inflammation effect or not is still unknown. METHODS: Carrageenan-induced paw oedema and LPS-activated macrophages are studied in this article. Injection of carrageenan into the foot of a mouse elicited an acute inflammatory response characterized by increase of foot volume and infiltration of neutrophils. While tumor necrosis factoralpha(TNF-alpha) secreted by activated macrophages was determined by ELISA and real-time PCR. RESULTS: All parameters of inflammation (foot volume, infiltration of neutrophils, amount of TNF-alpha and the level of TNF-alpha's mRNA) were attenuated by the hydrogen saline treatment. CONCLUSION: As a more convenient way than inhaling H2, hydrogen saline exhibits a protective effect against inflammation and it might provide a novel therapeutic approach for inflammatory diseases. PMID- 22296737 TI - Actual and undiagnosed HIV prevalence in a community sample of men who have sex with men in Auckland, New Zealand. AB - BACKGROUND: The prevalence of HIV infection and how this varies between subgroups is a fundamental indicator of epidemic control. While there has been a rise in the number of HIV diagnoses among men who have sex with men (MSM) in New Zealand over the last decade, the actual prevalence of HIV and the proportion undiagnosed is not known. We measured these outcomes in a community sample of MSM in Auckland, New Zealand. METHODS: The study was embedded in an established behavioural surveillance programme. MSM attending a gay community fair day, gay bars and sex-on-site venues during 1 week in February 2011 who agreed to complete a questionnaire were invited to provide an anonymous oral fluid specimen for analysis of HIV antibodies. From the 1304 eligible respondents (acceptance rate 48.5%), 1049 provided a matched specimen (provision rate 80.4%). RESULTS: HIV prevalence was 6.5% (95% CI: 5.1-8.1). After adjusting for age, ethnicity and recruitment site, HIV positivity was significantly elevated among respondents who were aged 30-44 or 45 and over, were resident outside New Zealand, had 6-20 or more than 20 recent sexual partners, had engaged in unprotected anal intercourse with a casual partner, had had sex with a man met online, or had injected drugs in the 6 months prior to survey. One fifth (20.9%) of HIV infected men were undiagnosed; 1.3% of the total sample. Although HIV prevalence did not differ by ethnicity, HIV infected non-European respondents were more likely to be undiagnosed. Most of the small number of undiagnosed respondents had tested for HIV previously, and the majority believed themselves to be either "definitely" or "probably" uninfected. There was evidence of continuing risk practices among some of those with known HIV infection. CONCLUSIONS: This is the first estimate of actual and undiagnosed HIV infection among a community sample of gay men in New Zealand. While relatively low compared to other countries with mature epidemics, HIV prevalence was elevated in subgroups of MSM based on behaviour, and diagnosis rates varied by ethnicity. Prevention should focus on raising condom use and earlier diagnosis among those most at risk, and encouraging safe behaviour after diagnosis. PMID- 22296738 TI - [Severe thrombocytopenia on admission to the intensive care unit in patients with multiple organ failure]. AB - OBJECTIVE: To evaluate the frequency of severe thrombocytopenia (STCP) (<= 50,000/MUl) in the first 24 hours in patients with multiple organ dysfunction syndrome, and the factors that influence its occurrence. DESIGN: A retrospective, observational study. AREA: Medical-surgical intensive care unit (ICU). Tertiary hospital. PATIENTS: Those with failure of at least two organs, according to SOFA criteria, with the exclusion of neurological and traumatologic critical cases. VARIABLES: Medical history, regular medication, baseline functional status, demographic variables, severity scores in ICU, multiple-organ failure data, course in ICU and main hospital data. RESULTS: A total of 587 patients were included; 6.3% (37 patients) presented with STCP during the first day of admission; 64.6% were men; SOFA 8 (5-10); APACHE II 18 (13-24); APACHE IV 59 (46 73); 32.5% were surgical patients. A total of 79.9% subsequently needed mechanical ventilation, and 71.4% required vasoactive drugs. Overall stay in ICU: 4 (2-10) days, main hospital stay 18 (9-35) days. A total of 29.2% died in the ICU; 11.7% developed STCP during admission to the ICU. Multivariate analysis found the main determining factors in the occurrence of thrombocytopenia on admission to be: history of hospitalization in the last year, albumin and bilirubin levels, and sepsis. CONCLUSION: The prevalence of STCP among critical patients was 6.3%. Its occurrence was associated with albumin and bilirubin levels, sepsis, and with patient admittance in the last year. PMID- 22296739 TI - Long-term outcomes with use of intravascular ultrasound for the treatment of coronary bifurcation lesions. AB - Percutaneous coronary intervention (PCI) of bifurcation lesions remains challenging with a higher risk of adverse outcomes. Whether adjunctive intravascular ultrasound (IVUS) imaging improves outcomes of PCI of bifurcation lesions remains unclear. This study sought to determine the long-term clinical outcomes associated with using IVUS for percutaneous treatment of coronary bifurcation lesions. From April 2003 through August 2010, 449 patients with 471 bifurcation lesions underwent PCI with (n = 247) and without (n = 202) the use of IVUS. Clinical outcomes (death, myocardial infarction [MI], periprocedural MI, stent thrombosis, target vessel revascularization [TVR], and target lesion revascularization [TLR]) were compared between patients undergoing PCI with and without IVUS using univariate and propensity score-adjusted analyses. Most patients (61%) presented with acute coronary syndrome and 89% of bifurcations lesions were Medina class 1,1,1. After propensity score adjustment, use of IVUS was associated with significantly lower rates of death or MI (odds ratio 0.38, 95% confidence interval 0.20 to 0.74, p = 0.005), death (odds ratio 0.40, 95% confidence interval 0.18 to 0.88, p = 0.02), MI (odds ratio 0.37, 95% confidence interval 0.14 to 0.98, p = 0.04), periprocedural MI (odds ratio 0.45, 95% confidence interval 0.20 to 0.97, p = 0.04), TVR (odds ratio 0.28, 95% confidence interval 0.14 to 0.53, p <0.0001), and TLR (odds ratio 0.27, 95% confidence interval 0.14 to 0.53, p = 0.0003) compared to no IVUS. In conclusion, IVUS guided treatment of complex bifurcation lesions was associated with significantly lower rates of adverse cardiac events at late follow-up. Further study is warranted to evaluate the role of IVUS guidance in improving long-term outcomes after PCI of bifurcation lesions. PMID- 22296740 TI - Ethnic and racial differences in the presence of idiopathic pulmonary fibrosis at death. AB - BACKGROUND: In studies of idiopathic pulmonary fibrosis (IPF), whites makeup the vast majority of subjects. Whether ethnic/racial differences in idiopathic pulmonary fibrosis occur in the general population is unknown. METHODS: To compare the presence of IPF between ethnic/racial groups of U.S. decedents from 1989 to 2007 by using the National Center for Health Statistics database. RESULTS: There were 251,058 U.S. decedents with IPF; 87.2% were non-Hispanic whites (White), 5.1% were non-Hispanic African American (black), 5.4% were Hispanic, and 2.2% were from other ethnic/racial groups (other). Whites coded with IPF died older than those in the other groups (77.9 years vs. 72.1 years for blacks, 75.3 years for Hispanics, and 75.6 years for others; p < 0.0001 for all pairwise comparisons). When controlling for age and for sex, compared with whites, both Hispanics and Others were more likely to be coded with IPF (OR = 1.47, 95% CI 1.44-1.49, p < 0.0001 and OR = 1.29, 95% CI 1.26-1.36, p < 0.0001 respectively), while blacks were significantly less likely to be coded with IPF (OR = 0.48, 95% CI 0.47-0.49, p < 0.0001). Among decedents with IPF, Hispanics were more likely, and blacks were less likely, than whites to die from IPF (OR = 1.24, 95% CI 1.20-1.29, p < 0.0001 and OR = 0.91, 95% CI 0.87-0.94, p < 0.0001). CONCLUSION: From 1989 to 2007, black decedents were less-and Hispanics were more likely than whites to die of/with IPF. Research is needed to determine if genetic differences between ethnic/racial groups explain these findings. PMID- 22296741 TI - ACCF/SCAI/STS/AATS/AHA/ASNC/HFSA/SCCT 2012 Appropriate use criteria for coronary revascularization focused update: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, Society for Cardiovascular Angiography and Interventions, Society of Thoracic Surgeons, American Association for Thoracic Surgery, American Heart Association, American Society of Nuclear Cardiology, and the Society of Cardiovascular Computed Tomography. AB - The American College of Cardiology Foundation (ACCF), Society for Cardiovascular Angiography and Interventions, Society of Thoracic Surgeons, and the American Association for Thoracic Surgery, along with key specialty and subspecialty societies, conducted an update of the appropriate use criteria (AUC) for coronary revascularization frequently considered. In the initial document, 180 clinical scenarios were developed to mimic patient presentations encountered in everyday practice and included information on symptom status, extent of medical therapy, risk level as assessed by noninvasive testing, and coronary anatomy. This update provides a reassessment of clinical scenarios the writing group felt to be affected by significant changes in the medical literature or gaps from prior criteria. The methodology used in this update is similar to the initial document, and the definition of appropriateness was unchanged. The technical panel scored the clinical scenarios on a scale of 1 to 9. Scores of 7 to 9 indicate that revascularization is considered appropriate and likely to improve patients' health outcomes or survival. Scores of 1 to 3 indicate revascularization is considered inappropriate and unlikely to improve health outcomes or survival. Scores in the mid-range (4 to 6) indicate a clinical scenario for which the likelihood that coronary revascularization will improve health outcomes or survival is uncertain. In general, as seen with the prior AUC, the use of coronary revascularization for patients with acute coronary syndromes and combinations of significant symptoms and/or ischemia is appropriate. In contrast, revascularization of asymptomatic patients or patients with low-risk findings on noninvasive testing and minimal medical therapy are viewed less favorably. The technical panel felt that based on recent studies, coronary artery bypass grafting remains an appropriate method of revascularization for patients with high burden of coronary artery disease (CAD). Additionally,percutaneous coronary intervention may have a role in revascularization of patients with high burden of CAD. The primary objective of the appropriate use criteria is to improve physician decision making and patient education regarding expected benefits from revascularization and to guide future research. PMID- 22296742 TI - Noradrenergic modulation of wakefulness/arousal. AB - The locus coeruleus-noradrenergic system supplies norepinephrine throughout the central nervous system. State-dependent neuronal discharge activity of locus coeruleus noradrenergic neurons has long-suggested a role of this system in the induction of an alert waking state. Work over the past two decades provides unambiguous evidence that the locus coeruleus, and likely other noradrenergic nuclei, exert potent wake-promoting actions via an activation of noradrenergic beta- and alpha1-receptors located within multiple subcortical structures, including the general regions of the medial septal area, the medial preoptic area and, most recently, the lateral hypothalamus. Conversely, global blockade of beta and alpha1-receptors or suppression of norepinephrine release results in profound sedation. The wake-promoting action of central noradrenergic neurotransmission has clinical implications for treatment of sleep/arousal disorders, such as insomnia and narcolepsy, and clinical conditions associated with excessive arousal, such as post-traumatic stress disorder. PMID- 22296743 TI - The prediction of intrusions following an analogue traumatic event: peritraumatic cognitive processes and anxiety-focused rumination versus rumination in response to intrusions. AB - Intrusions are often considered the hallmark of posttraumatic stress disorder (PTSD). Despite this, relatively little is known about factors that give rise to intrusions. Cognitive models of PTSD highlight the importance of pre-existing cognitive vulnerabilities, cognitive processing and anxiety during a traumatic event, as well as negative responses to trauma sequelae. However, few studies have examined multiple forms of peritraumatic processes, and rumination in response to trauma intrusions using analogue trauma tasks, and none have examined whether broader anxious ruminative processes contribute to intrusion development. In addition, little work has investigated the role of post-state anxiety in intrusions, and anxiety may be related to both peritraumatic processing and rumination. The current study employed a distressing film paradigm to examine key tenets of cognitive models of PTSD. Ninety-one female university students completed measures of anxiety, rumination in response to anxious symptoms, peritraumatic dissociation, data driven processing, lack of self referent processing, intrusions, and rumination in response to intrusions of the distressing film. Results revealed that peritraumatic dissociation, data driven processing, and self referent processing were associated with intrusion development, with lack of self referent processing being a strong predictor of intrusion development. Post-state anxiety and rumination in response to intrusions also predicted intrusion development. Discussion focuses on implications of cognitive processes and anxiety in theories of intrusion development. PMID- 22296745 TI - Obesogens: an environmental link to obesity. PMID- 22296744 TI - Role of environmental chemicals in diabetes and obesity: a National Toxicology Program workshop review. AB - BACKGROUND: There has been increasing interest in the concept that exposures to environmental chemicals may be contributing factors to the epidemics of diabetes and obesity. On 11-13 January 2011, the National Institute of Environmental Health Sciences (NIEHS) Division of the National Toxicology Program (NTP) organized a workshop to evaluate the current state of the science on these topics of increasing public health concern. OBJECTIVE: The main objective of the workshop was to develop recommendations for a research agenda after completing a critical analysis of the literature for humans and experimental animals exposed to certain environmental chemicals. The environmental exposures considered at the workshop were arsenic, persistent organic pollutants, maternal smoking/nicotine, organotins, phthalates, bisphenol A, and pesticides. High-throughput screening data from Toxicology in the 21st Century (Tox21) were also considered as a way to evaluate potential cellular pathways and generate -hypotheses for testing which and how certain chemicals might perturb biological processes related to diabetes and obesity. CONCLUSIONS: Overall, the review of the existing literature identified linkages between several of the environmental exposures and type 2 diabetes. There was also support for the "developmental obesogen" hypothesis, which suggests that chemical exposures may increase the risk of obesity by altering the differentiation of adipocytes or the development of neural circuits that regulate feeding behavior. The effects may be most apparent when the developmental exposure is combined with consumption of a high-calorie, high carbohydrate, or high-fat diet later in life. Research on environmental chemical exposures and type 1 diabetes was very limited. This lack of research was considered a critical data gap. In this workshop review, we outline the major themes that emerged from the workshop and discuss activities that NIEHS/NTP is undertaking to address research recommendations. This review also serves as an introduction to an upcoming series of articles that review the literature regarding specific exposures and outcomes in more detail. PMID- 22296746 TI - Intensity-modulated radiotherapy in head and neck cancer: results of the prospective study GORTEC 2004-03. AB - BACKGROUND AND PURPOSE: In 2003, the French Authority for Health (HAS) recommended the use of intensity modulated radiotherapy (IMRT) in prospective trial before its routine use. The Oncology and Radiotherapy Group for Head and Neck Cancer (GORTEC) proposed to evaluate prospectively acute and late toxicities, locoregional control and overall survival for patients treated for head and neck cancer (HNC) with IMRT and bilateral neck irradiation. MATERIALS AND METHODS: Between 2002 and 2008, 208 patients with HNC were treated with IMRT in 8 centres. There were 38 nasopharynx, 117 oropharynx, 25 pharyngo-larynx, 24 oral cavity and 4 unknown primary (28.5% stage I-II and 71% Stage III-IV). Ninety three patients (46%) had postoperative IMRT and 78 patients (37.5%) received concurrent chemotherapy. The doses were 70 Gy to the gross tumour, 66 Gy to the high-risk postoperative sites and 50 Gy to the subclinical disease. Toxicities were graded according to the RTOG-EORTC scales. RESULTS: The median follow-up was 25.3 months (range: 0.4-72 months). There were 29 local-regional failures: 24 were in-field, three were marginal and one was out-field. The two-year loco regional control and overall survival were 86% and 86.7%, respectively. At 18 months, grade >= 2 xerostomia was 16.1%. A mean dose to the spared parotid below 28 Gy led to significantly less grade >= 2 xerostomia (8.5% vs 24%) with a relative risk of 1.2 [95% CI: 1.02-1.41, p = 0.03]. Grade >= 2 xerostomia increased by approximately 3% per Gy of mean parotid dose up to 28, Gy then 7% per Gy above 33 Gy. CONCLUSIONS: IMRT for HN cancer seems to reduce late toxicities without jeopardising local control and overall survival. PMID- 22296747 TI - Managing a national radiation oncologist workforce: a workforce planning model. AB - PURPOSE: The specialty of radiation oncology has experienced significant workforce planning challenges in many countries. Our purpose was to develop and validate a workforce-planning model that would forecast the balance between supply of, and demand for, radiation oncologists in Canada over a minimum 10-year time frame, to identify the model parameters that most influenced this balance, and to suggest how this model may be applicable to other countries. METHODS: A forward calculation model was created and populated with data obtained from national sources. Validation was confirmed using a historical prospective approach. RESULTS: Under baseline assumptions, the model predicts a short-term surplus of RO trainees followed by a projected deficit in 2020. Sensitivity analyses showed that access to radiotherapy (proportion of incident cases referred), individual RO workload, average age of retirement and resident training intake most influenced balance of supply and demand. Within plausible ranges of these parameters, substantial shortages or excess of graduates is possible, underscoring the need for ongoing monitoring. CONCLUSIONS: Workforce planning in radiation oncology is possible using a projection calculation model based on current system characteristics and modifiable parameters that influence projections. The workload projections should inform policy decision making regarding growth of the specialty and training program resident intake required to meet oncology health services needs. The methods used are applicable to workforce planning for radiation oncology in other countries and for other comparable medical specialties. PMID- 22296748 TI - Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (IV): Basic principles and parameters for MR imaging within the frame of image based adaptive cervix cancer brachytherapy. AB - The GYN GEC-ESTRO working group issued three parts of recommendations and highlighted the pivotal role of MRI for the successful implementation of 3D image based cervical cancer brachytherapy (BT). The main advantage of MRI as an imaging modality is its superior soft tissue depiction quality. To exploit the full potential of MRI for the better ability of the radiation oncologist to make the appropriate choice for the BT application technique and to accurately define the target volumes and the organs at risk, certain MR imaging criteria have to be fulfilled. Technical requirements, patient preparation, as well as image acquisition protocols have to be tailored to the needs of 3D image-based BT. The present recommendation is focused on the general principles of MR imaging for 3D image-based BT. Methods and parameters have been developed and progressively validated from clinical experience from different institutions (IGR, Universities of Vienna, Leuven, Aarhus and Ljubljana) and successfully applied during expert meetings, contouring workshops, as well as within clinical and interobserver studies. It is useful to perform pelvic MRI scanning prior to radiotherapy ("Pre RT-MRI examination") and at the time of BT ("BT MRI examination") with one MR imager. Both low and high-field imagers, as well as both open and close magnet configurations conform to the requirements of 3D image-based cervical cancer BT. Multiplanar (transversal, sagittal, coronal and oblique image orientation) T2 weighted images obtained with pelvic surface coils are considered as the golden standard for visualisation of the tumour and the critical organs. The use of complementary MRI sequences (e.g. contrast-enhanced T1-weighted or 3D isotropic MRI sequences) is optional. Patient preparation has to be adapted to the needs of BT intervention and MR imaging. It is recommended to visualise and interpret the MR images on dedicated DICOM-viewer workstations, which should also assist the contouring procedure. Choice of imaging parameters and BT equipment is made after taking into account aspects of interaction between imaging and applicator reconstruction, as well as those between imaging, geometry and dose calculation. In a prospective clinical context, to implement 3D image-based cervical cancer brachytherapy and to take advantage of its full potential, it is essential to successfully meet the MR imaging criteria described in the present recommendations of the GYN GEC-ESTRO working group. PMID- 22296749 TI - Clinical outcome after hydrothermal ablation treatment of menorrhagia in patients with and without submucous myomas. AB - STUDY OBJECTIVE: To analyze the long-term efficacy of hydrothermal ablation (HTA) in women with a normal uterine cavity and submucous uterine myomas. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: Roskilde University Hospital surgical daycare unit. PATIENTS: One hundred sixty-six consecutive patients with abnormal uterine bleeding who underwent HTA from 2004 to 2008. All patients were asked to fill out a specific questionnaire that included questions related to postoperative bleeding patterns, complications, and satisfaction with the procedure. One hundred thirty-six patients (81.9%) completed the questionnaire, including 33 women (24.3%) with submucous myomas. INTERVENTION: The HTA procedure was performed in accordance with previous descriptions. MEASUREMENTS AND MAIN RESULTS: Mean (SD; 95% CI) follow-up was 33 (10.5; 25.5-31.8) months. Amenorrhea was achieved in 57 women with myomas (55.3%) and 17 women (51.5%) without myomas (p = .47). Postoperative light bleeding was reported in 26 women with myomas (25.2%) and 6 women (18.2%) without myomas. During follow-up, 13 women with myomas (12.6%) underwent hysterectomy, compared with 6 women without myomas (18.2%). Postoperatively, the mean (SD; 95% CI) number of days per month with bleeding was reduced in both groups, from 13.62 (7.90; 11.87-15.37) to 1.34 (2.32; 0.84-1.84) days in the group with myomas, and from 14.78 (8.81; 10.97-18.59), to 1.88 (4.38; 0.12-3.65) without myomas. Similarly, both groups reported improved quality of life: 74.8% and 72.7%, respectively (p = .59). Compared with patients with myomas 3 cm or smaller, patients with myomas larger than 3 cm demonstrated a significantly higher rate of severe bleeding postoperatively (p = .02). CONCLUSION: Our results demonstrate that HTA is associated with a high rate of amenorrhea in patients with or without submucous myomas. However, a significantly lower effect may be observed in patients with myomas larger than 3 cm. PMID- 22296750 TI - High prevalence of asthma in HIV-infected adults: new insights. PMID- 22296751 TI - Which disease is cured by Lactobacillus? PMID- 22296754 TI - Food protein-induced enterocolitis syndrome in an exclusively breast-fed infant an uncommon entity. PMID- 22296755 TI - Surfactant Protein D modulates allergen particle uptake and inflammatory response in a human epithelial airway model. AB - BACKGROUND: Allergen-containing subpollen particles (SPP) are released from whole plant pollen upon contact with water or even high humidity. Because of their size SPP can preferentially reach the lower airways where they come into contact with surfactant protein (SP)-D. The aim of the present study was to investigate the influence of SP-D in a complex three-dimensional human epithelial airway model, which simulates the most important barrier functions of the epithelial airway. The uptake of SPP as well as the secretion of pro-inflammatory cytokines was investigated. METHODS: SPP were isolated from timothy grass and subsequently fluorescently labeled. A human epithelial airway model was built by using human Type II-pneumocyte like cells (A549 cells), human monocyte derived macrophages as well as human monocyte derived dendritic cells. The epithelial cell model was incubated with SPP in the presence and absence of surfactant protein D. Particle uptake was evaluated by confocal microscopy and advanced computer-controlled analysis. Finally, human primary CD4+ T-Cells were added to the epithelial airway model and soluble mediators were measured by enzyme linked immunosorbent assay or bead array. RESULTS: SPP were taken up by epithelial cells, macrophages, and dendritic cells. This uptake coincided with secretion of pro-inflammatory cytokines and chemokines. SP-D modulated the uptake of SPP in a cell type specific way (e.g. increased number of macrophages and epithelial cells, which participated in allergen particle uptake) and led to a decreased secretion of pro inflammatory cytokines. CONCLUSION: These results display a possible mechanism of how SP-D can modulate the inflammatory response to inhaled allergen. PMID- 22296756 TI - Lateral transfer of tetrahymanol-synthesizing genes has allowed multiple diverse eukaryote lineages to independently adapt to environments without oxygen. AB - Sterols are key components of eukaryotic cellular membranes that are synthesized by multi-enzyme pathways that require molecular oxygen. Because prokaryotes fundamentally lack sterols, it is unclear how the vast diversity of bacterivorous eukaryotes that inhabit hypoxic environments obtain, or synthesize, sterols. Here we show that tetrahymanol, a triterpenoid that does not require molecular oxygen for its biosynthesis, likely functions as a surrogate of sterol in eukaryotes inhabiting oxygen-poor environments. Genes encoding the tetrahymanol synthesizing enzyme squalene-tetrahymanol cyclase were found from several phylogenetically diverged eukaryotes that live in oxygen-poor environments and appear to have been laterally transferred among such eukaryotes. PMID- 22296757 TI - Production of IL1-beta by ovarian cancer cells induces mesothelial cell beta1 integrin expression facilitating peritoneal dissemination. AB - BACKGROUND: A crucial step in the metastatic spread of ovarian cancer (OC) is the adhesion and implantation of tumor cells to the peritoneal mesothelium. In order to study this step in the cascade, we derived a pro-metastatic human ovarian carcinoma cell line (MFOC3) from the non-metastatic FOC3 line. METHODS: Molecular profiling of the isogeneic lines identified differentially expressed genes, and investigation for a role in dissemination for specific factors was achieved by development of a co-culture adhesion assay utilizing monolayers of human mesothelial cells. RESULTS: After murine intraperitoneal inoculation, the FOC3 cell line formed no metastases, but the MFOC3 subline formed metastases in > 80% of SCID mice. MFOC3 cells also adhered 2-3 times more avidly to mesothelial monolayers. This adhesion was inhibited by neutralizing antibodies to IL-1beta and enhanced by recombinant IL-1beta (p < 0.01). IL-1beta induced mesothelial cell beta1-integrin, and an antibody to this subunit also inhibited the adhesion of MFOC3 to mesothelial cells in vitro and significantly reduced metastases in vivo. Immunohistochemical analysis of a cohort of 96 ovarian cancer cases showed that negative IL-1beta expression was significantly associated with an improved overall survival rate. CONCLUSIONS: These results suggest that a IL-1beta/beta1 integrin axis plays a role in ovarian tumor cell adhesion to mesothelia, a crucial step in ovarian cancer dissemination. PMID- 22296758 TI - Barriers to women's participation in inter-conceptional care: a cross-sectional analysis. AB - BACKGROUND: We describe participation rates in a special interconceptional care program that addressed all commonly known barriers to care, and identify predictors of the observed levels of participation in this preventive care service. METHODS: A secondary analysis of data from women in the intervention arm of an interconceptional care clinical trial in Philadelphia (n = 442). Gelberg Andersen Behavioral Model for Vulnerable Populations to Health Services (herein called Andersen model) was used as a theoretical base. We used a multinomial logit model to analyze the factors influencing women's level of participation in this enhanced interconceptional care program. RESULTS: Although common barriers were addressed, there was variable participation in the interconceptional interventions. The Andersen model did not explain the variation in interconceptional care participation (Wald ch sq = 49, p = 0.45). Enabling factors (p = 0.058), older maternal age (p = 0.03) and smoking (p = < 0.0001) were independently associated with participation. CONCLUSIONS: Actively removing common barriers to care does not guarantee the long-term and consistent participation of vulnerable women in preventive care. There are unknown factors beyond known barriers that affect participation in interconceptional care. New paradigms are needed to identify the additional factors that serve as barriers to participation in preventive care for vulnerable women. PMID- 22296759 TI - Asiatic acid protects primary neurons against C2-ceramide-induced apoptosis. AB - Ceramides derived from sphingosine contribute to the apoptotic processes of neuronal cells in neurodegenerative disorders including Alzheimer's disease. This study investigates the potential neuroprotective effects of Asiatic acid, a triterpenoid derived from Centella asiatica, against C(2)-ceramides-induced cell death in primary cultured rat cortical neuronal cells. In primary neurons, Asiatic acid (0.01 to 1.0 MUmol/l) reduced C(2)-ceramide-induced cell death and mitochondria membrane potential loss in a concentration-dependent manner. Furthermore, Asiatic acid decreased cellular production of reactive oxygen species following C(2)-ceramide treatment. At a maximal concentration of 1.0 MUmol/l, Asiatic acid partly counteracted the pro-apoptotic effects of the C(2) ceramide by reducing the cytosolic release of HtrA2/Omi, the upregulation of Bax and caspase 3, as well as the dephosphorlyation of ERK1/2. Taken together, these data suggest that Asiatic acid protects neurons from C(2)-ceramide-induced cell death by antagonizing mitochondria-dependent apoptosis. PMID- 22296760 TI - Constitutive androstane receptor activation by 2,4,6-triphenyldioxane-1,3 suppresses the expression of the gluconeogenic genes. AB - The constitutive androstane receptor (CAR, NR1I3) has a central role in detoxification processes, regulating the expression of a set of genes involved in metabolism. The dual role of NR1I3 as both a xenosensor and as a regulator of endogenous energy metabolism has recently been accepted. Here, we investigated the mechanism of transcriptional regulation of the glucose metabolising genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) by the cis isomer of 2,4,6-triphenyldioxane-1,3 (cisTPD), a highly effective NR1I3 activator in rat liver. It was shown that expression of the gluconeogenic genes PEPCK and G6Pase was repressed by cisTPD treatment under fasting conditions. Western-blot analysis demonstrated a clear reduction in the intensity of PEPCK and G6Pase immunobands from the livers of cisTPD-treated animals relative to bands from the livers of control animals. Chromatin immunoprecipitation assays demonstrated that cisTPD prevents the binding of FOXO1 to the insulin response sequences in the PEPCK and G6Pase gene promoters in rat liver. Moreover, cisTPD activated NR1I3 inhibited NR2A1 (HNF-4) transactivation by competing with NR2A1 for binding to the NR2A1-binding element (DR1-site) in the gluconeogenic gene promoters. Thus, our results are consistent with the hypothesis that the cisTPD activated NR1I3 participates in the regulation of the gluconeogenic genes PEPCK and G6Pase. PMID- 22296761 TI - Prescribers' interactions with medication alerts at the point of prescribing: A multi-method, in situ investigation of the human-computer interaction. AB - PURPOSE: Few studies have examined prescribers' interactions with medication alerts at the point of prescribing. We conducted an in situ, human factors investigation of outpatient prescribing to uncover factors that influence the prescriber-alert interaction and identify strategies to improve alert design. METHODS: Field observations and interviews were conducted with outpatient prescribers at a major Veterans Affairs Medical Center. Physicians, clinical pharmacists, and nurse practitioners were recruited across five primary care clinics and eight specialty clinics. Prescribers were observed in situ as they ordered medications for patients and resolved alerts. Researchers collected 351 pages of typed notes across 102 hours of observations and interviews. An interdisciplinary team identified emergent themes via inductive qualitative analysis. RESULTS: Altogether, 320 alerts were observed among 30 prescribers and their interactions with 146 patients. Qualitative analysis uncovered 44 emergent themes and 9 overarching factors, which were organized into a framework that describes the prescriber-alert interaction. Prescribers' ability to act on alerts was impeded by the alert interface, which did not adequately support all prescriber types. CONCLUSIONS: This empiric study produced a novel framework for understanding the prescriber-alert interaction. Results revealed key components of the alert interface that influence prescribers and indicate a need for more universal design. Actionable design recommendations are presented and may be used to enhance alert design and patient safety. PMID- 22296762 TI - Results of a randomized controlled trial to assess the effects of a mobile SMS based intervention on treatment adherence in HIV/AIDS-infected Brazilian women and impressions and satisfaction with respect to incoming messages. AB - OBJECTIVE: To assess whether a warning system based on mobile SMS messages increases the adherence of HIV-infected Brazilian women to antiretroviral drug based treatment regimens and their impressions and satisfaction with respect to incoming messages. DESIGN: A randomized controlled trial was conducted from May 2009 to April 2010 with HIV-infected Brazilian women. All participants (n=21) had a monthly multidisciplinary attendance; each participant was followed over a 4 month period, when adherence measures were obtained. Participants in the intervention group (n=8) received SMS messages 30 min before their last scheduled time for a dose of medicine during the day. The messages were sent every Saturday and Sunday and on alternate days during the working week. Participants in the control group (n=13) did not receive messages. MEASUREMENTS: Self-reported adherence, pill counting, microelectronic monitors (MEMS) and an interview about the impressions and satisfaction with respect to incoming messages. RESULTS: The HIV Alert System (HIVAS) was developed over 7 months during 2008 and 2009. After the study period, self-reported adherence indicated that 11 participants (84.62%) remained compliant in the control group (adherence exceeding 95%), whereas all 8 participants in the intervention group (100.00%) remained compliant. In contrast, the counting pills method indicated that the number of compliant participants was 5 (38.46%) for the control group and 4 (50.00%) for the intervention group. Microelectronic monitoring indicated that 6 participants in the control group (46.15%) were adherent during the entire 4-month period compared to 6 participants in the intervention group (75.00%). According to the feedback of the 8 participants who completed the research in the intervention group, along with the feedback of 3 patients who received SMS for less than 4 months, that is, did not complete the study, 9 (81.81%) believed that the SMS messages aided them in treatment adherence, and 10 (90.90%) responded that they would like to continue receiving SMS messages. CONCLUSION: SMS messaging can help Brazilian women living with HIV/AIDS to adhere to antiretroviral therapy for a period of at least 4 months. In general, the results are encouraging because the SMS messages stimulated more participants in the intervention group to be adherent to their treatment, and the patients were satisfied with the messages received, which were seen as reminders, incentives and signs of affection by the health clinic for a marginalized population. PMID- 22296763 TI - Evaluation of cellular uptake and intracellular trafficking as determining factors of gene expression for amino acid-substituted gemini surfactant-based DNA nanoparticles. AB - BACKGROUND: Gene transfer using non-viral vectors offers a non-immunogenic and safe method of gene delivery. Cellular uptake and intracellular trafficking of the nanoparticles can impact on the transfection efficiency of these vectors. Therefore, understanding the physicochemical properties that may influence the cellular uptake and the intracellular trafficking can aid the design of more efficient non-viral gene delivery systems. Recently, we developed novel amino acid-substituted gemini surfactants that showed higher transfection efficiency than their parent compound. In this study, we evaluated the mechanism of cellular uptake of the plasmid/gemini surfactant/helper lipid nanoparticles and their effect on the transfection efficiency. RESULTS: Nanoparticles were incubated with Sf 1 Ep cells in the presence of different endocytic inhibitors and gene expression (interferon-gamma) was measured using ELISA. Clathrin-mediated and caveolae-mediated uptake were found to be equally contributing to cellular internalization of both P/12-7NH-12/L (parent gemini surfactant) and P/12-7NGK 12/L (amino acid-substituted gemini surfactant) nanoparticles. The plasmid and the helper lipid were fluorescently tagged to track the nanoparticles inside the cells, using confocal laser scanning microscopy. Transmission electron microscopy images showed that the P/12-7NGK-12/L particles were cylindrical while the P/12 7NH-12/L particles were spherical which may influence the cellular uptake behaviour of these particles. Dye exclusion assay and pH-titration of the nanoparticles suggested that high buffering capacity, pH-dependent increase in particle size and balanced DNA binding properties may be contributing to a more efficient endosomal escape of P/12-7NGK-12/L compared to the P/12-7NH-12/L nanoparticles, leading to higher gene expression. CONCLUSION: Amino-acid substitution in the spacer of gemini surfactant did not alter the cellular uptake pathway, showing similar pattern to the unsubstituted parent gemini surfactant. Glycyl-lysine substitution in the gemini spacer improved buffering capacity and imparted a pH-dependent increase of particle size. This property conferred to the P/12-7NGK-12/L nanoparticles the ability to escape efficiently from clathrin mediated endosomes. Balanced binding properties (protection and release) of the 12-7NGK-12 in the presence of polyanions could contribute to the facile release of the nanoparticles internalized via caveolae-mediated uptake. A more efficient endosomal escape of the P/12-7NGK-12/L nanoparticles lead to higher gene expression compared to the parent gemini surfactant. PMID- 22296765 TI - Oocyst output and transmission rates during successive infections with Eimeria acervulina in experimental broiler flocks. AB - The infection dynamics of Eimeria species determine the clinical manifestation of the disease coccidiosis in poultry flocks, and a better understanding of the dynamics may contribute to improvement of control measures. Our aim was to study the course of infection and the transmission of Eimeria acervulina in groups of broilers by quantifying the transmission rate parameter and oocyst output. Three transmission experiments were carried out with groups of 20 male SPF broilers. At 2 days of age, one bird in each trial was orally inoculated with five sporulated E. acervulina oocysts (D0 post-inoculation, pi). One day after inoculation (D1 pi), the inoculated bird was housed with 19 non-inoculated contact birds. Individual faecal droppings were examined daily from D3-D32 pi to quantify the number of oocysts per gram faeces. The inoculated bird started shedding oocysts at D5 pi and contact birds between D10 and D17 pi. Contact birds that became infected due to oocyst excretion by the inoculated bird were characterized as first generation contact birds (C1). Contact birds excreting from D15 pi onwards (C2) became infected after the first C1 birds had started shedding and were considered to belong to a successive generation of the flock infection. Oocyst output was significantly lower for C1 compared to C2 birds, but the transmission rate parameter remained constant for both infection generations. These results suggest that although oocyst load increases, the transmission rate of E. acervulina remains constant between successive generations of infection in a flock. PMID- 22296764 TI - Signaling in innate immunity and inflammation. AB - Inflammation is triggered when innate immune cells detect infection or tissue injury. Surveillance mechanisms involve pattern recognition receptors (PRRs) on the cell surface and in the cytoplasm. Most PRRs respond to pathogen-associated molecular patterns (PAMPs) or host-derived damage-associated molecular patterns (DAMPs) by triggering activation of NF-kappaB, AP1, CREB, c/EBP, and IRF transcription factors. Induction of genes encoding enzymes, chemokines, cytokines, adhesion molecules, and regulators of the extracellular matrix promotes the recruitment and activation of leukocytes, which are critical for eliminating foreign particles and host debris. A subset of PRRs activates the protease caspase-1, which causes maturation of the cytokines IL1beta and IL18. Cell adhesion molecules and chemokines facilitate leukocyte extravasation from the circulation to the affected site, the chemokines stimulating G-protein coupled receptors (GPCRs). Binding initiates signals that regulate leukocyte motility and effector functions. Other triggers of inflammation include allergens, which form antibody complexes that stimulate Fc receptors on mast cells. Although the role of inflammation is to resolve infection and injury, increasing evidence indicates that chronic inflammation is a risk factor for cancer. PMID- 22296766 TI - Observations on the free-living stages of cattle gastrointestinal nematodes. AB - A 4-year study on the free-living stages of cattle gastrointestinal nematodes was conducted to determine (a) the development time from egg to infective larvae (L3) inside the faecal pats, (b) the pasture infectivity levels over time, and (c) the survival of L3 on pasture. Naturally infected calves were allowed to contaminate 16 plots on monthly basis. Weekly monitoring of eggs per gram of faeces (epg) values and faecal cultures from these animals provided data for the contamination patterns and the relative nematode population composition. At the same time, faecal pats were shaped and deposited monthly onto herbage and sampled weekly to determine the development time from egg to L3. Herbage samples were collected fortnightly over a 16-month period after deposition to evaluate the pasture larval infectivity and survival of L3 over time. The development time from egg to L3 was 1-2 weeks in summer, 3-5 weeks in autumn, 4-6 weeks in winter, and 1-4 weeks in spring. The levels of contamination and pasture infectivity showed a clear seasonality during autumn-winter and spring, whilst a high mortality of larvae on pasture occurred in summer. Ostertagia spp., Cooperia spp. and Trichostrongylus spp. were predominant and a survival of L3 on pasture over a 1 year period was recorded in this study. PMID- 22296767 TI - Prognostic studies of canine and feline mammary tumours: the need for standardized procedures. AB - For several years, veterinary oncologists have been struggling with the prognosis of mammary tumours in dogs and cats. Translation of tumour characteristics into prognostic information is an invaluable tool for the use of the most appropriate therapies, as well as for planning innovative therapeutic trials. Moreover, canine and feline spontaneous mammary gland tumours are good models for the study of human breast cancer. Collecting and interpreting information regarding the prognosis of canine and feline mammary tumours is difficult due to the fact that different methods have been applied to study various components and characteristics. This review identifies some of the challenges of prognostic studies of spontaneous canine and feline mammary tumours and suggests standardized procedures to overcome these challenges and facilitate reproducibility and assessment of results. PMID- 22296768 TI - [Intestinal alterations in patients with a medullary lesion]. AB - Loss of bowel control is distressing for persons with a medullary lesion and affects their quality of life. The present study aims to provide an updated review of the topic. Impaired neural control of continence and defecation after a medullary lesion provokes bowel dysfunction, with a high prevalence of two main symptoms: fecal incontinence and constipation. The physiopathology of these disorders is correlated with the neurological characteristics of the lesion, and various physiopathologic patterns have been established that correlate with the clinical manifestations. Evaluation of bowel dysfunction in these patients is normally exclusively clinical and complementary examinations are rarely used, although they seem promising. Treatment is based on establishing a program of evacuation. However, despite correct application, the results can be unsatisfactory and consequently other therapeutic alternatives should be developed. PMID- 22296769 TI - MMP-14 is expressed in preeclamptic placentas and mediates release of soluble endoglin. AB - Soluble endoglin is an anti-angiogenic protein that is released from the placenta and contributes to both maternal endothelial dysfunction and the clinical features of severe preeclampsia. The mechanism through which soluble endoglin is released from the placenta is currently unknown; however, recent work in colorectal cancer identified matrix metalloproteinase 14 (MMP-14) as the cleavage protease of endoglin. To determine whether this is also the mechanism responsible for soluble endoglin release in preeclampsia, we investigated the expression of MMP-14 within the placenta and the effects of its inhibition on soluble endoglin release. Placentas were obtained from severe, early onset preeclamptic pregnancies (n = 8) and gestationally matched preterm controls (n = 8). MMP-14 was predominately localized to the syncytiotrophoblast. Results from a proximity ligation assay showed protein interactions between endogenous MMP-14 and endoglin within the preeclamptic placenta. To demonstrate that this interaction produces soluble endoglin, we treated trophoblastic BeWo cells with either a broad spectrum MMP inhibitor (GM6001) or MMP-14 siRNA. Both treatments produced a decrease in soluble endoglin (P <= 0.05). Treatment of mice bearing BeWo xenografts with GM6001 decreased circulating soluble endoglin levels in mouse serum (P <= 0.05). These findings indicate that MMP-14 is the likely cleavage protease of endoglin in the setting of preeclampsia. This approach provides a novel method for the development of potential therapeutics to reduce circulating soluble endoglin and ameliorate the clinical features of severe preeclampsia. PMID- 22296770 TI - Local signaling within stem cell niches: insights from Drosophila. AB - Tissue stem cells are found in specialized microenvironments (niches) where they are exposed to diverse systemic and local signals that are integrated with cell intrinsic factors to regulate stem cell behavior. In general, systemic signals are utilized to coordinate the response of tissues to acute or long-term changes that affect the whole organism, such as variations in nutrient availability or aging. In contrast, local signaling regulates tissue maintenance by balancing stem cell self-renewal with differentiation under homeostatic conditions and in response to local damage. In this review, we highlight the role of the JAK-STAT pathway in two Drosophila stem cell systems, the testis and intestine, and compare and contrast how activation of this pathway leads to tissue maintenance under both homeostatic conditions and in response to stress or injury. PMID- 22296771 TI - From stem cells to cancer stem cells: HIF takes the stage. AB - Hypoxia, a condition of insufficient oxygen availability, occurs during normal development as well as tumorigenesis. Cellular responses to hypoxia are primarily mediated by hypoxia-inducible factors (HIFs). Recent studies have revealed that dormant hematopoietic stem cells (HSCs) reside within hypoxic regions of the bone marrow and that HIF is a critical player in HSC homeostasis. The functional significance of HIF in maintaining stemness also applies to cancer stem cells in hematological malignancies. These findings indicate that better understanding of the mechanisms underlying HIF functions in stem cells should permit the development of new therapies for tissue regeneration and cancer. PMID- 22296772 TI - How well are we meeting haematological cancer survivors' preferences for involvement in treatment decision making? AB - OBJECTIVE: This study aimed to examine preferred and perceived roles of haematological cancer survivors in treatment decision making. METHODS: Participants were within three years of diagnosis and registered with a cancer registry in one Australian state. 732 eligible survivors were invited to complete a paper and pencil survey. RESULTS: 268 survivors completed the survey (37% response rate). The majority of participants (46%) preferred a passive role in decision making. Thirty percent of participants preferred to make the decision in collaboration with the doctor, whereas 26% preferred an active role in decision making. Just over half of respondents (56%) reported an exact match between their preferred and perceived roles. Where discordance between preferred and perceived roles were identified, survivors were more likely to report having been more passively than actively involved compared to their preferred roles. CONCLUSION: There is considerable variation in haematological cancer survivors' preferred and perceived roles in treatment decision making. PRACTICE IMPLICATIONS: This study highlights the need to improve clinical communication to ensure that patient experiences align with their preferences for involvement in treatment decision making. PMID- 22296773 TI - Buddha in room eight. PMID- 22296774 TI - Gastrin-releasing peptide receptor expression in non-cancerous bronchial epithelia is associated with lung cancer: a case-control study. AB - BACKGROUND: Normal bronchial tissue expression of GRPR, which encodes the gastrin releasing peptide receptor, has been previously reported by us to be associated with lung cancer risk in 78 subjects, especially in females. We sought to define the contribution of GRPR expression in bronchial epithelia to lung cancer risk in a larger case-control study where adjustments could be made for tobacco exposure and sex. METHODS: We evaluated GRPR mRNA levels in histologically normal bronchial epithelial cells from 224 lung cancer patients and 107 surgical cancer free controls. Associations with lung cancer were tested using logistic regression models. RESULTS: Bronchial GRPR expression was significantly associated with lung cancer (OR = 4.76; 95% CI = 2.32-9.77) in a multivariable logistic regression (MLR) model adjusted for age, sex, smoking status and pulmonary function. MLR analysis stratified by smoking status indicated that ORs were higher in never and former smokers (OR = 7.74; 95% CI = 2.96-20.25) compared to active smokers (OR = 1.69; 95% CI = 0.46-6.33). GRPR expression did not differ by subject sex, and lung cancer risk associated with GRPR expression was not modified by sex. CONCLUSIONS: GRPR expression in non-cancerous bronchial epithelium was significantly associated with the presence of lung cancer in never and former smokers. The association in never and former smokers was found in males and females. Association with lung cancer did not differ by sex in any smoking group. PMID- 22296775 TI - Muscle fatigue increases the amplitude of fluctuations of tangential forces during isometric contractions. AB - The orientation of the resultant force during a given contraction depends on the architecture of the muscles involved, and cooperation among muscles may induce force fluctuations in multiple directions. A novel setup for recording three dimensional forces was developed to assess the effects of muscle fatigue on submaximal contractions. Fifteen subjects performed isometric dorsiflexions, elbow flexions, knee extensions, plantarflexions, and trunk extensions (12 s, 2.5 80% of maximal voluntary force) before and after a fatigue protocol. Electromyography (EMG) was recorded from relevant muscles. The standard deviation of force in the three directions and the agonist EMG amplitude increased with target force (p<.045), while the coefficient of variation of force and total excursions of the center of pressure showed maximal values at low target forces, reaching a plateau at moderate forces. Fatigue induced higher force fluctuations in task-related and tangential directions and increased agonist EMG amplitude for all muscle groups (p<.04). Fluctuations of tangential forces were greater during knee extensions compared with other muscle groups (p<.007). The present data demonstrate that fatigue increases the amplitude of force fluctuations in task related and tangential forces. Moreover, alternation of activity between multiple synergist muscles is associated with increased fluctuations of tangential forces, especially during fatigue. PMID- 22296776 TI - Decoding neurodevelopment: findings on environmental exposures and synaptic plasticity. PMID- 22296777 TI - Temporal differences in gamma-hydroxybutyrate overdoses involving injecting drug users versus recreational drug users in Helsinki: a retrospective study. AB - BACKGROUND: Gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL) have been profiled as 'party drugs' used mainly at dance parties and in nightclubs on weekend nights. The purpose of this study was to examine the frequency of injecting drug use among GHB/GBL overdose patients and whether there are temporal differences in the occurrence of GHB/GBL overdoses of injecting drug and recreational drug users. METHODS: In this retrospective study, the ambulance and hospital records of suspected GHB- and GBL overdose patients treated by the Helsinki Emergency Medical Service from January 1st 2006 to December 31st 2007 were reviewed. According to the temporal occurrence of the overdose, patients were divided in two groups. In group A, the overdose occurred on a Friday Saturday or Saturday-Sunday night between 11 pm-6 am. Group B consisted of overdoses occurring on outside this time frame. RESULTS: Group A consisted of 39 patient contacts and the remaining 61 patient contacts were in group B. There were statistically significant differences between the two groups in (group A vs. B, respectively): history of injecting drug abuse (33% vs. 59%, p = 0.012), reported polydrug and ethanol use (80% vs. 62%, p = 0.028), the location where the patients were encountered (private or public indoors or outdoors, 10%, 41%, 41% vs. 25%, 18%, 53%, p = 0.019) and how the knowledge of GHB/GBL use was obtained (reported by patient/bystanders or clinical suspicion, 72%, 28% vs. 85%, 10%, p = 0.023). Practically all (99%) patients were transported to emergency department after prehospital care. CONCLUSION: There appears to be at least two distinct groups of GHB/GBL users. Injecting drug users represent the majority of GHB/GBL overdose patients outside weekend nights. PMID- 22296778 TI - An appeal to medical journal editors: the need for a full description of laboratory methods and specimen handling in clinical study reports. Statement by the Consortium of Laboratory Medicine Journal Editors. PMID- 22296779 TI - Transient beneficial effects of excitatory theta burst stimulation in a patient with phonological agraphia after left supramarginal gyrus infarction. AB - We report a patient showing isolated phonological agraphia after an ischemic stroke involving the left supramarginal gyrus (SMG). In this patient, we investigated the effects of focal repetitive transcranial magnetic stimulation (rTMS) given as theta burst stimulation (TBS) over the left SMG, corresponding to the Brodmann area (BA) 40. The patient and ten control subjects performed a dictational words and nonwords writing task before, and 5 and 30 min after they received excitatory intermittent TBS (iTBS) over the left BA 40, the right hemisphere homologous to BA 40, the Wernicke's area, or the primary visual cortex. ITBS over the left SMG lead to a brief facilitation of phonological non words writing to dictation. This case study report illustrates that rTMS is able to influence, among other language functions, the phonological loading processes during the written language production in stroke patients. PMID- 22296780 TI - Stenting of the unprotected left main coronary artery in patients with severe aortic stenosis prior to percutaneous valve interventions. AB - AIMS: High-risk patients with severe aortic stenosis (AS) who are candidates for transcatheter valve implantation (TAVI) or balloon aortic valvuloplasty (BAV) may additionally require revascularization of the unprotected left main coronary artery (UPLM). We aimed to assess the feasibility and procedural safety of UPLM stenting in such patients. METHODS AND RESULTS: Ten cases of UPLM stenting prior to BAV or TAVI at three medical centers over a 2-year period were identified. Mean age was 84+/-4 years, aortic valve area was 0.70+/-0.12 cm(2), left ventricular ejection fraction was 58%+/-3%, and logistic EuroScore was 32+/-17. Intraaortic balloon counterpulsation was used in three patients. A single stent was used in seven patients, and two stents were used in three patients. One patient received a bare-metal stent, and the others received drug-eluting stents. No procedural complications occurred, and the patients were hemodynamically stable. Three patients subsequently underwent BAV, and seven underwent TAVI. During 6 months of follow-up, two patients died: one due to AS restenosis 6 months after BAV and one due to vascular complications 18 days after TAVI (34 days after UPLM stenting). CONCLUSIONS: Stenting of the UPLM in patients with severe AS prior to percutaneous valve intervention seems feasible and safe. This approach may enable more patients to achieve comprehensive percutaneous therapy for severe coronary and valvular disease. PMID- 22296781 TI - Randomized trial of insulin versus usual care in reducing restenosis after coronary intervention in patients with diabetes. the STent Restenosis And Metabolism (STREAM) study. AB - BACKGROUND: Diabetes status is an independent marker of restenosis after percutaneous coronary intervention (PCI). Previous studies suggest that metabolic abnormalities associated with diabetes increase stent restenosis by promoting intimal hyperplasia. Preclinical studies have indicated that insulin therapy reduces intimal hyperplasia. The objective of this study was to determine whether insulin-mediated glucose lowering reduces in-stent restenosis in patients with diabetes undergoing PCIs. METHODS: We conducted a prospective, randomized, multicenter, open-labeled study with blinded outcomes. Patients were randomized 1:1 to daily bedtime subcutaneous NPH insulin (Novo Nordisk) versus usual therapy with oral hypoglycemic agents. The main outcomes were change in volume of intimal hyperplasia within the stent measured by intravascular ultrasound and late lumen loss by quantitative coronary angiography at 6 months post-PCI. RESULTS: Seventy eight patients (36 insulin, 42 usual care) were randomized. Eight patients in each group received drug-eluting stents. The insulin group achieved greater reductions in both glycosylated hemoglobin A1c (mean+/-S.D.) (insulin: 8.0%+/ 1.2% to 6.7%+/-0.7% vs. control: 7.5%+/-1.2% to 7.1%+/-1.0 %, P=.0038) and fasting glucose (insulin: 9.3+/-3.8 to 5.8+/-1.7 vs. usual care: 8.4+/-2.4 to 7.7+/-2.0 mmol/l, P<.0001). There were no hypoglycemic events. At 6 months, there were no significant differences in either intravascular-ultrasound-determined neointimal volume (insulin: 41.2+/-38.9 vs. usual care: 48.4+/-40.2 mm(3), P=.33) or late lumen loss by angiography (insulin: 1.29+/-0.74 mm vs. usual care: 1.02+/ 0.71 mm, P=.17). CONCLUSIONS: Addition of a single bedtime dose of insulin in patients with diabetes does not influence in-stent restenosis. PMID- 22296782 TI - Movement of the external ear in human embryo. AB - INTRODUCTION: External ears, one of the major face components, show an interesting movement during craniofacial morphogenesis in human embryo. The present study was performed to see if movement of the external ears in a human embryo could be explained by differential growth. METHODS: In all, 171 samples between Carnegie stage (CS) 17 and CS 23 were selected from MR image datasets of human embryos obtained from the Kyoto Collection of Human Embryos. The three dimensional absolute position of 13 representative anatomical landmarks, including external and internal ears, from MRI data was traced to evaluate the movement between the different stages with identical magnification. Two different sets of reference axes were selected for evaluation and comparison of the movements. RESULTS: When the pituitary gland and the first cervical vertebra were selected as a reference axis, the 13 anatomical landmarks of the face spread out within the same region as the embryo enlarged and changed shape. The external ear did move mainly laterally, but not cranially. The distance between the external and internal ear stayed approximately constant. Three-dimensionally, the external ear located in the caudal ventral parts of the internal ear in CS 17, moved mainly laterally until CS 23. When surface landmarks eyes and mouth were selected as a reference axis, external ears moved from the caudal lateral ventral region to the position between eyes and mouth during development. CONCLUSION: The results indicate that movement of all anatomical landmarks, including external and internal ears, can be explained by differential growth. Also, when the external ear is recognized as one of the facial landmarks and having a relative position to other landmarks such as the eyes and mouth, the external ears seem to move cranially. PMID- 22296783 TI - Psychometric properties of the Greek Diabetes Treatment Satisfaction Questionnaire. AB - OBJECTIVES: Measurement of treatment satisfaction in diabetes is important as it has been shown to be associated with positive outcomes, reduced disease cost and better health. The aim of this study was to assess the construct validity and internal consistency reliability of the Greek version of the Diabetes Treatment Satisfaction Questionnaire (DTSQ). METHODS: A sample of type II diabetes patients (N = 172) completed the DTSQ status version, the SF-36 health survey and also provided data regarding treatment method, clinical and socio-demographic status. Instrument structure, reliability (Cronbach's a) and construct validity (convergent, discriminative, concurrent and known-groups) were assessed. RESULTS: The DTSQ measurement properties were confirmed in the Greek version with confirmatory factor analysis (CFA). Scale reliability was high (Cronbach's a = 0.92). Item-scale internal consistency and discriminant validity were also good, exceeding the designated success criteria. Significant correlations were observed between DTSQ items/overall score and SF-36 scales/component scores, which were hypothesized to measure similar dimensions. Known groups' comparisons yielded consistent support of the construct validity of the instrument. CONCLUSIONS: The instrument was well-accepted by the patients and its psychometric properties were similar to those reported in validation studies of other language versions. Further research, incorporating a longitudinal study design, is required for examining test-retest reliability and responsiveness of the instrument, which were not addressed in this study. Overall, the present results confirm that the DTSQ status version is a reasonable choice for measuring diabetes treatment satisfaction in Greece. PMID- 22296784 TI - Interaction between alcohol drinking and obesity in relation to colorectal cancer risk: a case-control study in Newfoundland and Labrador, Canada. AB - BACKGROUND: While substantive epidemiological literature suggests that alcohol drinking and obesity are potential risk factors of colorectal cancer (CRC), the possible interaction between the two has not been adequately explored. We used a case-control study to examine if alcohol drinking is associated with an increased risk of CRC and if such risk differs in people with and without obesity. METHODS: Newly diagnosed CRC cases were identified between 1999 and 2003 in Newfoundland and Labrador (NL). Cases were frequency-matched by age and sex with controls selected using random digit dialing. Cases (702) and controls (717) completed self-administered questionnaires assessing health and lifestyle variables. Estimates of alcohol intake included types of beverage, years of drinking, and average number of alcohol drinks per day. Odds ratios were estimated to investigate the associations of alcohol independently and when stratified by obesity status on the risk of CRC. RESULTS: Among obese participants (BMI >= 30), alcohol was associated with higher risk of CRC (OR: 2.2; 95% CI: 1.2-4.0) relative to the non-alcohol category. Among obese individuals, 3 or more different types of drinks were associated with a 3.4-fold higher risk of CRC relative to non-drinkers. The risk of CRC also increased with drinking years and drinks daily among obese participants. However, no increased risk was observed in people without obesity. CONCLUSION: The effect of alcohol of drinking on CRC seems to be modified by obesity. PMID- 22296785 TI - Development and calibration of a standard for the protein content of granulocyte colony-stimulating factor products. AB - This collaborative study characterizes a homogeneous standard for the protein content determination of granulocyte colony-stimulating factor (G-CSF) products with traceability of the measurement. The Kjeldahl method was used to determine the average protein content of G-CSF bulk as 2.505 mg/ml (95% C.I: 2.467-2.543 mg/ml, GCV 4.0%). Using G-CSF bulk as a traceability benchmark, the protein content of the final freeze-dried standard using reverse phase HPLC (RP-HPLC) was 215.4 MUg protein per ampoule (95% C.I: 212.407-218.486 MUg/ampoule, GCV 3.4%). A comparative study showed that there was no difference between using Filgrastim CRS (European Pharmacopeia G-CSF reference standard) and freeze-dried homogeneous standard when quantifying G-CSF protein content by RP-HPLC (P > 0.05). However, there were significant differences in the G-CSF protein content obtained using a serum albumin standard by Lowry assay and a G-CSF standard with RP-HPLC. Therefore, use of RP-HPLC with a freeze-dried homogeneous standard would eliminate the systematic errors introduced when using a serum albumin standard because of the differences in protein composition between the standard and the sample. It would also be helpful to use this method to compare the quality of G CSF biosimilar products in situations where the protein content has been calibrated using various standards. PMID- 22296786 TI - Efficacy evaluation of live Escherichia coli expression Brucella P39 protein combined with CpG oligodeoxynucleotides vaccine against Brucella melitensis 16M, in BALB/c mice. AB - Brucella is gram-negative bacteria responsible for brucellosis in a wide variety of animals and humans. BALB/c mice were immunized with live Escherichia coli expression the p39 gene of Brucella melitensis, a gene coding for the periplasmic binding protein. Mice were injected with either E. coli BL21 (DE3) pEt15b or E. coli BL21 (DE3) pEt15b-p39 alone or adjuvanted with either CpG oligodeoxynucleotides (CpG ODN) or non-CpG ODN. E. coli BL21 (DE3) pEt15b-p39 with CpG ODN or with non-CpG ODN mice groups showed a significant IFN-gamma production and T-cell proliferation as a reaction to P39 antigen. In addition, antibody responses (IgG, IgG1 and IgG2a), were only found in these two mice groups. A higher level of protection against B. melitensis 16M were observed in mice immunized with E. coli BL21 (DE3) pEt15b-p39 and CpG ODN comparing with those immunized with E. coli BL21 (DE3) pEt15b-p39 alone or with non-CpG ODN. No protection against B. melitensis 16M was observed in mice immunized with E. coli BL21 (DE3) pEt15b alone or with the adjuvant. Rev.1 protection at 4 and 8 weeks post-challenge was more effective than that observed with E. coli BL21 (DE3) pEt15b-p39 and CpG ODN. PMID- 22296787 TI - Predicting relapse prior to transplantation in chronic myeloid leukemia by integrating expert knowledge and expression data. AB - MOTIVATION: Selecting a small number of signature genes for accurate classification of samples is essential for the development of diagnostic tests. However, many genes are highly correlated in gene expression data, and hence, many possible sets of genes are potential classifiers. Because treatment outcomes are poor in advanced chronic myeloid leukemia (CML), we hypothesized that expression of classifiers of advanced phase CML when detected in early CML [chronic phase (CP) CML], correlates with subsequent poorer therapeutic outcome. RESULTS: We developed a method that integrates gene expression data with expert knowledge and predicted functional relationships using iterative Bayesian model averaging. Applying our integrated method to CML, we identified small sets of signature genes that are highly predictive of disease phases and that are more robust and stable than using expression data alone. The accuracy of our algorithm was evaluated using cross-validation on the gene expression data. We then tested the hypothesis that gene sets associated with advanced phase CML would predict relapse after allogeneic transplantation in 176 independent CP CML cases. Our gene signatures of advanced phase CML are predictive of relapse even after adjustment for known risk factors associated with transplant outcomes. PMID- 22296788 TI - WegoLoc: accurate prediction of protein subcellular localization using weighted Gene Ontology terms. AB - SUMMARY: We present an accurate and fast web server, WegoLoc for predicting subcellular localization of proteins based on sequence similarity and weighted Gene Ontology (GO) information. A term weighting method in the text categorization process is applied to GO terms for a support vector machine classifier. As a result, WegoLoc surpasses the state-of-the-art methods for previously used test datasets. WegoLoc supports three eukaryotic kingdoms (animals, fungi and plants) and provides human-specific analysis, and covers several sets of cellular locations. In addition, WegoLoc provides (i) multiple possible localizations of input protein(s) as well as their corresponding probability scores, (ii) weights of GO terms representing the contribution of each GO term in the prediction, and (iii) a BLAST E-value for the best hit with GO terms. If the similarity score does not meet a given threshold, an amino acid composition-based prediction is applied as a backup method. AVAILABILITY: WegoLoc and User's guide are freely available at the website http://www.btool.org/WegoLoc CONTACT: smchiks@ks.ac.kr; dougnam@unist.ac.kr SUPPLEMENTARY INFORMATION: Supplementary data is available at http://www.btool.org/WegoLoc. PMID- 22296789 TI - A gene-based test of association using canonical correlation analysis. AB - MOTIVATION: Canonical correlation analysis (CCA) measures the association between two sets of multidimensional variables. We reasoned that CCA could provide an efficient and powerful approach for both univariate and multivariate gene-based tests of association without the need for permutation testing. RESULTS: Compared with a commonly used permutation-based approach, CCA (i) is faster; (ii) has appropriate type-I error rate for normally distributed quantitative traits; (iii) provides comparable power for small to medium-sized genes (<100 kb); (iv) provides greater power when the causal variants are uncommon; (v) provides considerably less power for larger genes (>=100 kb) when the causal variants have a broad minor allele frequency (MAF) spectrum. Application to a GWAS of leukocyte levels identified SAFB and a histone gene cluster as novel putative loci harboring multiple independent variants regulating lymphocyte and neutrophil counts. PMID- 22296790 TI - Variable capacity of 13 hepatitis B virus surface antigen assays for the detection of HBsAg mutants in blood samples. AB - BACKGROUND: Natural variation and mutations in the envelope protein (S) of hepatitis B virus can translate into HBsAg variants no longer detectable by conventional HBsAg assays. OBJECTIVES: The aim of the study was to assess the performance of 13 commercial assays currently used for screening and clinical analysis of HBsAg variants. STUDY DESIGN: The limit of detection (LOD) for each assay was established using two reference standards (WHO HBsAg 00/588 and the SFTS French reference). Sensitivity was evaluated using different panels. Panel 1 included 25 recombinant HBs variants at three concentrations, panels 2 and 4 included 8 recombinant HBsAg variants and 9 wild-type proteins (genotypes A-F), respectively, panel 3 included 16 natural HBsAg variants. RESULTS: LODs ranged from 0.011 to 0.095 IU/ml with the WHO standard, and from 0.021 to 0.326 ng/ml with the French reference. The overall percentage of positive signals using HBsAg variants ranged from 62.9% to 97.9%. Three substitutions: T123, D144A and G145, were negative at all concentrations with at least one assay. DISCUSSION: Our findings show that, although they fulfil CE requirements for analytical sensitivity (LODs below 0.13 IU/ml), HBsAg assays may vary in their capacity to detect HBsAg variants. This limit in diagnosis performance should encourage the health regulatory agencies to include HBsAg variant panels in the evaluation process. PMID- 22296791 TI - Comparison of two broadly multiplexed PCR systems for viral detection in clinical respiratory tract specimens from immunocompromised children. AB - BACKGROUND: The detection of viral respiratory tract infections has evolved greatly with the development of PCR based commercial systems capable of simultaneously detecting a wide variety of pathogens. OBJECTIVES: Evaluate the relative performance of two commercial broad range systems for the detection of viral agents in clinical respiratory tract specimens from immunocompromised children. STUDY DESIGN: A total of 176 patient samples were included in the analysis, representing only the first sample collected for each patient, and excluding failed reactions. Samples were de-identified and assayed in parallel using two different, broadly multiplexed PCR systems: ResPlexTM II Panel v2.0 (ResPlex), Qiagen, Hilden, Germany and FilmArray((r)) Respiratory Panel (FilmArray), Idaho Technology Inc., Salt Lake City, UT. Method comparison was based upon pair-wise concordance of results according to patient age, viral target and number of targets detected. RESULTS: The two systems showed an overall concordance, by patient, of 83.8% (p=0.0001). FilmArray detected at least one target in 68.8% of samples, while ResPlex detected at least one target in 56.8%. ResPlex failed to detect 20.7% of FilmArray positives, and FilmArray failed to detect 4% of ResPlex positives. The relative performance of each system (including which system detected a higher number of positive samples) varied when stratified by target viral pathogen. CONCLUSIONS: Broadly multiplexed PCR is an effective means of detecting large numbers of clinically relevant respiratory viral pathogens. PMID- 22296792 TI - A new highly automated extraction system for quantitative real-time PCRs from whole blood samples: routine monitoring of opportunistic infections in immunosuppressed patients. AB - BACKGROUND: Rapid, high throughput extraction systems are needed to monitor viral infections in immunosuppressed patients. OBJECTIVES: Evaluate the performance of the MagNA Pure 96TM extraction system, and compare it to the COBAS AmpliprepTM for quantitative real-time PCR from whole blood samples. STUDY DESIGN: Compare the MagNA Pure LCTM, COBAS AmpliprepTM and MagNA Pure 96TM using ten-fold dilutions of blood samples containing cytomegalovirus. Evaluate analytical performances of the MagNA Pure 96TM from test samples containing cytomegalovirus. Evaluate clinical performances from 209 blood samples collected prospectively, extracted with the COBAS AmpliprepTM and the MagNA Pure 96TM systems and tested for cytomegalovirus, Epstein-Barr, BK and JC viruses. RESULTS: All three extraction systems gave similar results with dilutions of a cytomegalovirus positive sample. Analytical tests showed that the limit of detection was 500 copies/ml, specificity was 100%, with no cross-contamination. Quantification was linear from 3.0 to 6.0 log(10)copies/ml. Intra-assay variation was 8.3-0.9% and inter-assay variation 8.8-5.2%. Clinical specimens extracted with the MagNA Pure 96TM and COBAS AmpliprepTM instruments agreed well for cytomegalovirus (r=0.54; p=0.07), Epstein-Barr virus (0.69; p=0.0005) and BK virus (0.85; p=0.01). All 55 samples were negative for JC virus. Mean loads were similar for cytomegalovirus (0.17 log(10)copies/ml) and BK virus (-0.24 log(10)copies/ml) while that of Epstein-Barr virus was slightly lower (1.02 log(10)copies/ml). CONCLUSIONS: The MagNA Pure 96TM instrument is an easy-to-use, reliable high throughput platform for extracting nucleic acid from clinical whole blood specimens. PMID- 22296793 TI - Pacific region influenza surveillance for oseltamivir resistance. AB - BACKGROUND: Hawaii and the United States-affiliated Pacific islands (USAPI) host over 8 million travelers annually, most of whom originate in Asia, Australia, and the Americas where prevalence of oseltamivir resistance in 2009 pandemic influenza A (H1N1) has been reported to be 2.5-3.5%. OBJECTIVE: To survey a collection of samples from Hawaii and the USAPI that had tested positive for the 2009 pandemic influenza A (H1N1) virus by RTI-PCR to assess whether antiviral resistance emerged in these island communities during the 2009 H1N1 pandemic. STUDY DESIGN: We examined RNA extracted from Hawaiian and USAPI cases for the neuraminidase H275Y mutation associated with oseltamivir resistance by pyrosequencing. RESULTS: Two hundred and sixty-three (263) 2009 pandemic influenza A (H1N1) positive specimens were tested and 263/263 (100%) were shown to lack the mutation most commonly associated with oseltamivir resistance. CONCLUSIONS: There was no evidence of oseltamivir resistant A(H1N1)pdm09 virus during the 2009 pandemic in the Pacific islands despite considerable travel exposure. Geographic isolation, the lack of a "second wave" of pandemic influenza, judicious antiviral use, aggressive vaccination, and below average tourism due to the global economic crisis may have been contributing factors. Continued surveillance and vigilance is necessary to monitor unpredictable influenza activity. PMID- 22296794 TI - [Bibliometric analysis of International Scientific production on primary care]. AB - OBJECTIVE: To present an international view of the scientific production in the field of primary care in the period 1985-2004. DESIGN: Retrospective, observational study. Bibliometric analysis. LOCATION: Medline database. WebSPIRS access through version 4.3. We analysed two periods: 2000-2004 (cross-sectional) and 1985-2004 (developmental). Search based on "MeSH Major" with descriptors: Primary Care or Primary Health Care, Family Practice, Family Physicians, Nurse Practitioners, and Entry Terms associated with these. KEY MEASURES: We analysed the bibliometric indicators of production, circulation, dispersion, and visibility. RESULTS: In 2000-2004, published 20911 articles were published, 0.73% of total production. There was a growth rate (1985-2004) of 221%, which was 2.4 times more than average. Transience rate was 83.17%. The English language is predominant (88.81%) over 34 languages, with Spanish being the next (2.6%). Sixteen countries produce 95.67% of the articles. Spain occupies the 7th place. Universities (52%) are the most productive institutions. There are 1074 different journals with the 10 most productive being: Br J Gen Pract, Adv Nurse Pract, Aust Fam Physician, Fam Pract, Fam Med, BMJ, Aten Primary Health Serv J, Can Fam Physician, J Fam Pract. The proportion of trials (5.43%) in PC is similar to other disciplines and has increased by 453% (1985-2004). CONCLUSIONS: The production of Primary care is about 1% of the total scientific output, with a noticeable and higher than average growth over 20 years. The proportion of clinical trials is similar to other disciplines. Although Anglo-Saxon countries and journals are the highest producers, Spain and the journal Aten Primaria is among those highlighted. PMID- 22296795 TI - [Nutritional assessment in elderly patients in a Family Medicine Unit]. PMID- 22296796 TI - [Variability in prescribing penicillins in the Segovia (Spain) Health Area]. PMID- 22296798 TI - [Analysis of the rational use of anti-hypertensives in the Murcia (Spain) region]. AB - OBJECTIVE: The objective of this study was to determine the pattern of use of antihypertensive drugs in the Murcia Region, comparing the results with the national data, and detecting problems in order to make improvements, or establish hypotheses and to plan new studies. DESIGN: Pharmacoepidemiological study (from 2004 to 2008) in accordance with the recommendations from World Heath Organization. SETTING: : Murcia Region. PARTICIPANTS: Annual census of each year. MAIN MEASUREMENTS: The use of antihypertensive drugs was measured by the daily doses per 1000 inhabitans-day (DHD). RESULTS: The use of antihypertensive drugs has significantly increased from 196.6 DHD to 235.8 DHD. The antihypertensives more used at the end of 2008 were: angiotensin II receptor blockers-ARB- (38.6%) and angiotensin converting enzyme inhibitors-ACEI- (21.8%). There has been a tendency to change the use of rennin-angiotensin system blockers-RASB-, with an increase in ARB of 77.5% and and a decrease in ACEI 9.5%. The comparison with the national data shows qualitative and quantitative differences in the pattern of antihypertensive drugs used during the studied period. CONCLUSIONS: The use of antihypertensive drugs in Murcia is less than in the rest of Spain. Therefore, this may be due to a problem of under treatment of this illness or other cardiovascular illnesses in the region. A greater use of ARB in Murcia and a lower use of ACEI was observed in Murcia. The differences found suggest that further studies are required to clarify their origins and causes, with the objective of achieving a more rational and efficient use of these drugs. PMID- 22296799 TI - [Negative outcomes associated with medication]. PMID- 22296800 TI - [Exercise and type 2 diabetes mellitus]. PMID- 22296801 TI - Organ specific mapping of in vivo redox state in control and cigarette smoke exposed mice using EPR/NMR co-imaging. AB - In vivo mapping of alterations in redox status is important for understanding organ specific pathology and disease. While electron paramagnetic resonance imaging (EPRI) enables spatial mapping of free radicals, it does not provide anatomic visualization of the body. Proton MRI is well suited to provide anatomical visualization. We applied EPR/NMR co-imaging instrumentation to map and monitor the redox state of living mice under normal or oxidative stress conditions induced by secondhand cigarette smoke (SHS) exposure. A hybrid co imaging instrument, EPRI (1.2 GHz)/proton MRI (16.18 MHz), suitable for whole body co-imaging of mice was utilized with common magnet and gradients along with dual EPR/NMR resonators that enable co-imaging without sample movement. The metabolism of the nitroxide probe, 3-carbamoyl-proxyl (3-CP), was used to map the redox state of control and SHS-exposed mice. Co-imaging allowed precise 3D mapping of radical distribution and reduction in major organs such as the heart, lungs, liver, bladder and kidneys. Reductive metabolism was markedly decreased in SHS-exposed mice and EPR/NMR co-imaging allowed quantitative assessment of this throughout the body. Thus, in vivo EPR/NMR co-imaging enables in vivo organ specific mapping of free radical metabolism and redox stress and the alterations that occur in the pathogenesis of disease. PMID- 22296802 TI - Enzyme-nanoparticle conjugates at oil-water interface for amplification of electrochemical immunosensing. AB - In the current research, the preparation of biocatalytic capsule (Ab(2)-catalytic capsule) was based on utilizing "oil" (organic compound) to entrap the nano Au/HRP/HAFP bioconjugates, which were produced by horseradish peroxidase (HRP) and HRP labeled anti-AFP (HAFP) co-conjugated on gold nanoparticles (nano-Au). For the first time, a signal amplification strategy was introduced by the prepared biocatalytic capsule as labels for electrochemical immunodetection of alpha-1-fetoprotein (AFP). The transmission electron microscopy (TEM) images indicated that the biocatalytic capsules were successfully synthesized. The cyclic voltammetry (CV) experiments provided the evidence that the prepared capsule exhibited high catalytic activity for the reduction of H(2)O(2). Besides, a biocompatible monolayer (collagen-TiO(2)) was introduced to immobilize a nano Au layer to fabricate the primary antibody on the electrode surface. After the prepared biocatalytic capsule was captured to the electrode surface to form the sandwich type immunoassay, the enhanced sensitivity was obtained with a detection limit of 29 pg/mL. The proposed immunoassay also presented good stability, selectivity and storage stability. PMID- 22296803 TI - Analysis of energy-based algorithms for RNA secondary structure prediction. AB - BACKGROUND: RNA molecules play critical roles in the cells of organisms, including roles in gene regulation, catalysis, and synthesis of proteins. Since RNA function depends in large part on its folded structures, much effort has been invested in developing accurate methods for prediction of RNA secondary structure from the base sequence. Minimum free energy (MFE) predictions are widely used, based on nearest neighbor thermodynamic parameters of Mathews, Turner et al. or those of Andronescu et al. Some recently proposed alternatives that leverage partition function calculations find the structure with maximum expected accuracy (MEA) or pseudo-expected accuracy (pseudo-MEA) methods. Advances in prediction methods are typically benchmarked using sensitivity, positive predictive value and their harmonic mean, namely F-measure, on datasets of known reference structures. Since such benchmarks document progress in improving accuracy of computational prediction methods, it is important to understand how measures of accuracy vary as a function of the reference datasets and whether advances in algorithms or thermodynamic parameters yield statistically significant improvements. Our work advances such understanding for the MFE and (pseudo-)MEA based methods, with respect to the latest datasets and energy parameters. RESULTS: We present three main findings. First, using the bootstrap percentile method, we show that the average F-measure accuracy of the MFE and (pseudo-)MEA based algorithms, as measured on our largest datasets with over 2000 RNAs from diverse families, is a reliable estimate (within a 2% range with high confidence) of the accuracy of a population of RNA molecules represented by this set. However, average accuracy on smaller classes of RNAs such as a class of 89 Group I introns used previously in benchmarking algorithm accuracy is not reliable enough to draw meaningful conclusions about the relative merits of the MFE and MEA-based algorithms. Second, on our large datasets, the algorithm with best overall accuracy is a pseudo MEA-based algorithm of Hamada et al. that uses a generalized centroid estimator of base pairs. However, between MFE and other MEA based methods, there is no clear winner in the sense that the relative accuracy of the MFE versus MEA-based algorithms changes depending on the underlying energy parameters. Third, of the four parameter sets we considered, the best accuracy for the MFE-, MEA-based, and pseudo-MEA-based methods is 0.686, 0.680, and 0.711, respectively (on a scale from 0 to 1 with 1 meaning perfect structure predictions) and is obtained with a thermodynamic parameter set obtained by Andronescu et al. called BL* (named after the Boltzmann likelihood method by which the parameters were derived). CONCLUSIONS: Large datasets should be used to obtain reliable measures of the accuracy of RNA structure prediction algorithms, and average accuracies on specific classes (such as Group I introns and Transfer RNAs) should be interpreted with caution, considering the relatively small size of currently available datasets for such classes. The accuracy of the MEA-based methods is significantly higher when using the BL* parameter set of Andronescu et al. than when using the parameters of Mathews and Turner, and there is no significant difference between the accuracy of MEA-based methods and MFE when using the BL* parameters. The pseudo-MEA-based method of Hamada et al. with the BL* parameter set significantly outperforms all other MFE and MEA-based algorithms on our large data sets. PMID- 22296804 TI - Sex-related difference in left ventricular mass in nonhypertensive young adults: role of arterial pressure. AB - BACKGROUND: Blood pressure (BP) is higher in men than in women at similar ages through adult life. Interestingly, a similar pattern is detected in left ventricular mass (LVM), classically attributed to differences in body size. However, the existing difference in BP between sexes might be relevant in determining LVM and it has been not fully investigated. Therefore, we set out to determine the impact of nonhypertensive levels of BP on the sex-associated LVM difference. METHODS: We conducted population-based study including 283 young students (52% male; age 20.62 +/- 1.31 years). BP was determined twice using standard mercury sphygmomanometers in 2 occasions. LVM was determined with M-mode echocardiography. To dissect the relative contribution of BP, volume load, and body size to the sex-related difference in LVM, an analysis of covariance was performed. RESULTS: Mean systolic and diastolic BP were 10.00 +/- 0.96 and 4.59 +/- 0.78 mm Hg higher and LVM was 34.87 +/- 3.12 g larger in men than in women, respectively (P < 0.01, t test). When LVM was adjusted to mean BP, the sex difference was reduced by 16%. When LVM was adjusted to body size and hemodynamic load, this difference was reduced by 68.5%. CONCLUSIONS: We report in a sample of young nonhypertensive students a difference in LVM between women and men that is partially explained (16%) by sex differences in BP, supporting an early effect of BP on cardiac mass even in the absence of hypertension. A more relevant effect could be expected as the population ages. PMID- 22296805 TI - Order out of chaos: elucidating the opposing effects of air pollutants and heat on blood pressure. PMID- 22296806 TI - Assessment of cardiometabolic risk among shift workers in Hungary. AB - AIM: Shift workers may be at risk of different diseases. In order to assess cardiometabolic risk in shift workers, a cross-sectional study was performed among active workers. METHODS: A total of 481 workers (121 men, 360 women) were investigated; most of them were employees in light industry (58.2%) or in public services (23.9%). Past medical history was recorded and physical examination was performed. Questionnaires were used to characterize daily activity. Fasting venous blood sample was collected for measuring laboratory parameters. Data from shift workers (n = 234, age: 43.9 +/- 8.1 years) were compared to those of daytime workers (n = 247, age: 42.8 +/- 8.5 years), men and women were analyzed separately. RESULTS: In men, systolic blood pressure was higher in shift workers compared to daytime workers (133 +/- 8 vs 126 +/- 17 mmHg; p < 0.05). In women, weight (73.6 +/- 15.5 vs 67.7 +/- 13.2 kg; p < 0.001), body mass index (27.5 +/- 5.7 vs 25.0 +/- 4.3 kg/m2; p<0.001) and the prevalence rate of hypertension in the past medical history (24.4 vs 13.4%; p < 0.01) were higher in shift workers compared to daytime workers. In addition, the proportion of current smokers was higher (37.7 vs 21.7%; p < 0.001) and HDL-cholesterol level was lower (1.56 +/- 0.32 vs 1.68 +/- 0.36 mmol/l; p < 0.01) in female shift workers than in female daytime workers. Both in men and in women, rotating shift workers spent less time sleeping both on working days and on non-working days, spent less time with sport activity, drank more coffee and they spent less time working per day, especially in light physical work, compared to daytime workers. In addition, low and middle educational levels were most frequently found among rotating shift workers as opposed to the daytime workers where high educational level was more common. CONCLUSION: Middle-aged active shift workers, especially women, have a less healthy lifestyle and are at higher cardiometabolic risk as compared to daytime workers. Our study highlights the importance of measures for identifying and preventing cardiometabolic risk factors in shift workers. PMID- 22296807 TI - Ectopic ossification presenting as osteoid metaplasia in a salivary mucocele in a Shih Tzu dog. AB - BACKGROUND: Salivary mucocele is an accumulation of saliva in a single or multiloculated cavity lined by connective tissue that is contiguous to a salivary gland-duct complex and is the most common condition affecting the salivary glands in dogs. Occasionally, different types of metaplastic lesions, such as squamous and osseous metaplasia - which are rare lesions in animals - can be observed in association with salivary mucocele. CASE PRESENTATION: A right facial enlargement was suddenly observed in a 4-year-old non-spayed female Shih-Tzu dog. The lesion presented itself as a soft and fluctuant mass located in the right side of the face near to the neck. Histologically, the mass consisted of a cavitary formation without an epithelial lining. Additionally, microscopic examination revealed the presence of osteoid-producing cells which gave rise to areas of bone formation, probably induced by irritation due to the presence sialoliths. Such cells and bone formations were also present in the cavity wall, consequently leading us to classify the condition as a salivary mucocele with osseous metaplasia. CONCLUSIONS: In the present case, the pathogenesis was probably associated with the presence of sialoliths, which can behave as etiological agents for the metaplastic lesion. The occurrence of osteoid metaplasia is a rare peculiar condition in the canine salivar y gland, and due to the rarity and lack of information about this specific disease, no clinical data can yet be associated with the development of salivary mucocele with osseous metaplasia in dogs. PMID- 22296808 TI - RPE cell senescence: a key contributor to age-related macular degeneration. AB - Age-related macular degeneration (AMD) is the leading cause of blindness in industrialized countries. Although much progress has been made recently in the management of later stages of the disease, no agents have yet been developed for the early stages or for prophylactic use. Furthermore, even the treatments for the later stages have limited effectiveness. The process of developing improved treatments for AMD is complicated by the existence of several theories concerning the cause of the disorder, each suggesting a different strategy for finding effective therapeutics. One of the potential contributors to AMD pathology is retinal pigment epithelial (RPE) cell senescence. The present paper hypothesizes that RPE senescence plays a central role in the etiology of AMD. This hypothesis is supported by the ability of RPE cell senescence to account for the signs, risk factors, and successful treatment modalities of the disorder. This hypothesis also points to several new prophylactic and treatment strategies for AMD. PMID- 22296809 TI - Can transcranial brain-targeted bright light treatment via ear canals be effective in relieving symptoms in seasonal affective disorder? A pilot study. AB - Bright light therapy (BLT) is widely accepted as first-line treatment of seasonal affective disorder (SAD). However, the mechanism of action of BLT is still widely unknown. On the other hand, in mammals, light penetrates the skull bone and reaches the brain, and extra ocular transcranial phototransduction has physiological influences such as changed reproductive cycles and increased brain serotonin levels. Therefore, we challenged the existing conceptual framework that light therapy would only be mediated through the eyes. Consequently, we run a pilot study on the putative effect of transcranial bright light in the treatment of SAD. The light was produced using light-emitting diodes (LEDs), which were attached to earplugs. The amount of photic energy was 6.0-8.5 lumens in both ear canals, and the length of treatment was 8 or 12 min five times a week during a four-week study period. Subjects were recruited through advertisements in the city of Oulu, Finland (latitude 65 degrees 01'N) during 14 January 2009-03 February 2009. The final patient series consisted of 13 (aged 37.1 +/- 7.2 years) physically healthy indoor workers suffering from SAD according to DSM-IV-TR criteria. Severity of depressive symptoms was assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17) and Beck Depression Inventory (BDI)-21. Furthermore, severity of anxiety symptoms was measured by the 14-item Hamilton Anxiety Rating Scale (HAMA). The HAMD-17 mean sum score at screening was 23.1 +/- 1.6. Ten out of 13 SAD patients (76.9%) achieved full remission (i.e., HAMD-17 sum score <= 7), and 92.3% (12/13) at least 50% reduction in HAMD-17 sum scores at "Week 4". By using a mixed regression model of repeated measures (AR-1) controlling for age, gender, and HAMD-17 mean sum score at screening, significant differences were found comparing the HAMD-17 mean sum scores of "Week 0" with the corresponding scores at the "Week 3" (t=-2.05, p=0.045) and "Week 4" visit (t= 2.77, p=0.008). Correspondingly, significant differences were found comparing the BDI-21 mean sum scores (15.2 +/- 6.7) of "Week 0" with the corresponding scores at the "Week 3" (t=-2.37, p=0.021) and "Week 4" visit (t=-3.65, p<0.001). The HAMA mean sum score at screening was 20.5 +/- 5.4. During the study period, 12 out of 13 (92.3%) patients achieved at least 50% reduction in their HAMA sum scores, and in 10 out of 13 patients (76.9%), the HAMA sum score was <7. In conclusion, it is hard to believe that our findings could be explained solely by placebo effect. Consequently, the basic assumptions underlying extraocular photoreception in humans deserve to be reconsidered. Given that a proper placebo treatment can be implemented via ear canals, further investigations with randomized placebo-controlled and/or dose-finding study designs regarding the extraocular transcranial bright light in the treatment of SAD are called for. PMID- 22296810 TI - Burn size and survival probability in paediatric patients in modern burn care: a prospective observational cohort study. AB - BACKGROUND: Patient survival after severe burn injury is largely determined by burn size. Modern developments in burn care have greatly improved survival and outcomes. However, no large analysis of outcomes in paediatric burn patients with present treatment regimens exists. This study was designed to identify the burn size associated with significant increases in morbidity and mortality in paediatric patients. METHODS: We undertook a single-centre prospective observational cohort study using clinical data for paediatric patients with burns of at least 30% of their total body surface area (TBSA). Patients were stratified by burn size in 10% increments, ranging from 30% to 100% TBSA, with a secondary assignment made according to the outcome of a receiver operating characteristic (ROC) analysis. Statistical analysis was done with Student's t test, chi(2) test, logistic regression, and ROC analysis, as appropriate, with significance set at p<0.05. FINDINGS: 952 severely burned paediatric patients were admitted to the centre between 1998 and 2008. All groups were comparable in age (mean 7.3 [SD 5.3] years, ranging from 6.1 [5.1] years in the 30-39% TBSA group to 9.6 [5.4] years in the 90-100% TBSA group) and sex distribution (628 [66%] boys, ranging from 59% [73/123] in the 60-69% TBSA group to 82% [42/51] in the 90-100% TBSA group). 123 (13%) patients died (increasing from 3% [five of 180] in the 30-39% TBSA group to 55% [28/51] in the 90-100% TBSA group; p<0.0001), 154 (16%) developed multiorgan failure (increasing from 6% [ten] in the 30-39% TBSA group to 45% [23] in the 90-100% TBSA group; p<0.0001), and 89 (9%) had sepsis (increasing from 2% [three] in the 30-39% TBSA group to 26% [13] in the 90-100% TBSA group; p<0.0001). Burn size of 62% TBSA was a crucial threshold for mortality (odds ratio 10.07, 95% CI 5.56-18.22, p<0.0001). INTERPRETATION: We established that, in a modern paediatric burn care setting, a burn size of roughly 60% TBSA is a crucial threshold for postburn morbidity and mortality. On the basis of these findings, we recommend that paediatric patients with greater than 60% TBSA burns be immediately transferred to a specialised burn centre. Furthermore, at the burn centre, patients should be treated with increased vigilance and improved therapies, in view of the increased risk of poor outcome associated with this burn size. FUNDING: Shriners Hospitals for Children, US National Institutes of Health, US National Institute on Disability and Rehabilitation Research, Institute for Translational Sciences, CFI Leaders Opportunity Fund, Physicians' Services Incorporated Foundation. PMID- 22296811 TI - Survival of children with burn injuries. PMID- 22296812 TI - [Colonization management of methicillin resistant Staphylococcus aureus in patients and health professional in the haemodialysis unit in a situation of high risk of endemic disease: looking for zero nasal carriers?]. AB - AIMS: To describe the dynamics of colonization by methicillin resistant Staphylococcus aureus (MRSA) detected in the Haemodialysis Unit (UHD) of the Hospital San Pedro de Alcantara of Caceres due to the detection of catheter associated infections. Additionally, we attempt to evaluate the effectiveness of preventive strategies introduced. METHODS: Nasal swab tests were performed in order to detect MRSA colonization in patients and health professionals from August 2008 to January 2009, according to the Consensus GEIH-SEIMC Y SEMPSPH Consensus. An active surveillance was performed with treatment and control of the carriers until negative results were achieved. A consensus document was drawn up in the UHD with registered preventive measures and work systems were reviewed. Prevalence, cumulative incidence, colonization pressure (carrier ratio per day/total patients or experts per day) were calculated. A chi-square test was performed, as well as a Z test for the comparison ratio. RESULTS: The nasal swabs of 54 acute and chronic patients on haemodialysis showed an initial carrier prevalence of 29.6%; cumulative incidence in patients of 42.6%. Nasal swabs of 48 professionals had a cumulative incidence of 39.5%. There was a parallel decrease in colonization pressure in patients and specialists. After five months A smear was performed 5 months later on 40 patients and 26 specialists, which showed no carriers among the patients, and one among the health professionals. CONCLUSION: We detected a high number of MRSA carriers among patients and Health professionals from the Haemodialysis Unit. Screening and treatment measures were effective for the decolonization of this population. It is important to adopt long-term strategies for active surveillance for the rapid detection of alert situations. PMID- 22296813 TI - [Impact and health care burden in the emergency department and a tertiary care hospital during the influenza A (H1N1) pandemic]. PMID- 22296814 TI - Endophthalmitis caused by Phialophora verrucosa: a case report and literature review of Phialophora ocular infections. PMID- 22296815 TI - mGluR5 receptors in the basolateral amygdala and nucleus accumbens regulate cue induced reinstatement of ethanol-seeking behavior. AB - Pharmacological blockade of the type 5 metabotropic glutamate receptor (mGluR5) attenuates cue-induced reinstatement of ethanol-seeking behavior, yet the brain regions involved in these effects are not yet known. The purpose of the present study was to determine if local blockade of mGluR5 receptors in the basolateral amygdala (BLA) and/or the nucleus accumbens (NAc), two brain regions known to be involved in stimulus-reward associations, attenuate the reinstatement of ethanol seeking behavior induced by ethanol-paired cues. As a control for possible non specific effects, the effects of mGluR5 blockade in these regions on cue-induced reinstatement of sucrose-seeking were also assessed. Male Wistar rats were implanted with bilateral microinjection cannulae aimed at the BLA or NAc. Following recovery, animals were trained to self-administer ethanol (10% w/v) or 45 mg sucrose pellets on an FR1 schedule of reinforcement in 30 min daily sessions using a sucrose fading procedure. Following stabilization of responding, animals underwent extinction training. Next, animals received infusions of vehicle or the selective mGluR5 antagonist MTEP (3 MUg/MUl) into the BLA or NAc prior to cue-induced reinstatement testing sessions. mGluR5 blockade eliminated cue-induced reinstatement of alcohol - but not sucrose-seeking behavior. Results from this study indicate that mGluR5 receptors in the BLA and NAc mediate cue induced reinstatement of ethanol-seeking behavior, and provide two potential neuroanatomical sites of action where systemically administered mGluR5 antagonists attenuate cue-induced reinstatement. These data are consistent with previous findings that cue-induced reinstatement of ethanol-seeking increases neuronal activity and glutamatergic transmission in these two regions. PMID- 22296816 TI - An artificial neural network to safely reduce the number of ambulance ECGs transmitted for physician assessment in a system with prehospital detection of ST elevation myocardial infarction. AB - BACKGROUND: Pre-hospital electrocardiogram (ECG) transmission to an expert for interpretation and triage reduces time to acute percutaneous coronary intervention (PCI) in patients with ST elevation Myocardial Infarction (STEMI). In order to detect all STEMI patients, the ECG should be transmitted in all cases of suspected acute cardiac ischemia. The aim of this study was to examine the ability of an artificial neural network (ANN) to safely reduce the number of ECGs transmitted by identifying patients without STEMI and patients not needing acute PCI. METHODS: Five hundred and sixty ambulance ECGs transmitted to the coronary care unit (CCU) in routine care were prospectively collected. The ECG interpretation by the ANN was compared with the diagnosis (STEMI or not) and the need for an acute PCI (or not) as determined from the Swedish coronary angiography and angioplasty register. The CCU physician's real time ECG interpretation (STEMI or not) and triage decision (acute PCI or not) were registered for comparison. RESULTS: The ANN sensitivity, specificity, positive and negative predictive values for STEMI was 95%, 68%, 18% and 99%, respectively, and for a need of acute PCI it was 97%, 68%, 17% and 100%. The area under the ANN's receiver operating characteristics curve for STEMI detection was 0.93 (95% CI 0.89-0.96) and for predicting the need of acute PCI 0.94 (95% CI 0.90-0.97). If ECGs where the ANN did not identify a STEMI or a need of acute PCI were theoretically to be withheld from transmission, the number of ECGs sent to the CCU could have been reduced by 64% without missing any case with STEMI or a need of immediate PCI. CONCLUSIONS: Our ANN had an excellent ability to predict STEMI and the need of acute PCI in ambulance ECGs, and has a potential to safely reduce the number of ECG transmitted to the CCU by almost two thirds. PMID- 22296817 TI - Isolated lateral rectus muscle involvement as a presenting sign of euthyroid Graves disease. PMID- 22296818 TI - High prevalence of amblyopia risk factors in preverbal children with nasolacrimal duct obstruction. PMID- 22296819 TI - Ocular myeloid sarcoma in a 10-year-old child. PMID- 22296820 TI - Socio-demographic factors and psychological distress in Indigenous and non Indigenous Australian adults aged 18-64 years: analysis of national survey data. AB - BACKGROUND: Indigenous Australians are known to be at greater risk of morbidity and mortality from mental health related conditions, but most available data relate to the use of mental health services, and little is known about other aspects of social and emotional wellbeing. Using the first available nationally representative data, we examined the prevalence and patterning of psychological distress among Indigenous Australian adults and compared these with corresponding data from the non-Indigenous population. METHODS: The analysis used weighted data on psychological distress, as measured by a modified Kessler Psychological Distress score (K5), and a range of socio-demographic measures for 5,417 Indigenous and 15,432 non-Indigenous adults aged 18-64 years from two nationally representative surveys. Very high psychological distress (VHPD) was defined as a K5 score >= 15 (possible range = 5-25). RESULTS: Indigenous adults were about three times more likely than non-Indigenous adults to be classified with VHPD: 14.5% (95% confidence interval (CI) 12.9-16.0%) versus 5.5% (95% CI 5.0-5.9%). After adjusting for age, most socio-demographic variables were significantly associated with VHPD in both populations, although the relative odds were generally larger among non-Indigenous people. Indigenous people in remote areas had a lower prevalence of VHPD than their non-remote counterparts, and only marital status, main language, and food insecurity were significantly associated with VHPD in remote areas. CONCLUSIONS: Higher absolute levels of VHPD combined with smaller socio-demographic gradients in the Indigenous population suggest the importance of risk factors such as interpersonal racism, marginalization and dispossession, chronic stress and exposure to violence that are experienced by Indigenous Australians with common and/or cross-cutting effects across the socioeconomic spectrum. The lower prevalence of VHPD and lack of association with many socio-demographic variables in remote areas suggests either that the instrument may be less valid for Indigenous people living in remote areas or that living in an Indigenous majority environment (such as exists in most remote communities) may mitigate the risk of psychological distress to some degree. PMID- 22296821 TI - DNA/nickel oxide nanoparticles/osmium(III)-complex modified electrode toward selective oxidation of l-cysteine and simultaneous detection of l-cysteine and homocysteine. AB - The modification of glassy carbon (GC) electrode with electrodeposited nickel oxide nanoparticles (NiOxNPs) and deoxyribonucleic acid (DNA) is utilized as a new efficient platform for entrapment of osmium (III) complex. Surface morphology and electrochemical properties of the prepared nanocomposite modified electrode (GC/DNA/NiOxNPs/Os(III)-complex) were investigated by FESEM, cyclic voltammetry and electrochemical impedance spectroscopy techniques. Cyclic voltammetric results indicated the excellent electrocatalytic activity of the resulting electrode toward oxidation of l-cysteine (CySH) at reduced overpotential (0.1 V vs. Ag/AgCl). Using chronoamperometry to CySH detection, the sensitivity and detection limit of the biosensor are obtained as 44 MUA mM(-1) and 0.07 MUM with a concentration range up to 1000 MUM. The electrocatalytic activity of the modified electrode not only for oxidation of low molecular-mass biothiols derivatives such as, glutathione, l-cystine, l-methionine and electroactive biological species ( dopamine, uric acid, glucose) is negligible but also for very similar biothiol compound (homocysteine) no recognizable response is observed at the applied potential window. Furthermore, the simultaneous voltammetric determination of l-cysteine and homocysteine compounds without any separation or pretreatment process was reported for the first time in this work. Finally, the applicability of sensor for the analysis of CySH concentration in complex serum samples was successfully demonstrated. Highly selectivity, excellent electrocatalytic activity and stability, remarkable antifouling property toward thiols and their oxidation products, as well as the ability for simultaneous detection of l-cysteine and homocysteine are remarkably advantageous of the proposed DNA based biosensor. PMID- 22296822 TI - Simple protein structure-sensitive chronopotentiometric analysis with dithiothreitol-modified Hg electrodes. AB - We have shown that proteins produce at bare mercury electrodes a well-developed chronopotentiometric peak H. At sufficiently high current densities and low ionic strengths, this peak is sensitive to changes in protein structures. At higher ionic strengths this sensitivity can be lost but it can be restored, when instead of bare, thiol-modified Hg electrodes are used. Here we studied properties of the dithiothreitol (DTT) layer at the hanging mercury drop electrode and showed that at low concentrations (5 MUM-200 MUM) the DTT is adsorbed as a dithiol with both SH groups attached to the surface. At higher DTT concentrations than 1mM, a densely packed pinhole-free layer is formed with the DTT molecules bound to the electrode surface by a single -SH group, oriented perpendicularly to the surface. We found that, if a sufficiently high DTT concentration is used, preparation of the DTT-modified Hg electrodes can be omitted and proteins can be co-adsorbed with DTT on liquid Hg or solid amalgam electrodes without the loss of sensitivity for changes in protein structures. The newly observed properties of the DTT self assembled monolayers (SAMs) at Hg electrodes appear important for designing new types of solid amalgam electrode arrays for electrochemical analysis of proteins. PMID- 22296823 TI - Glutathione peroxidase activity in seminal plasma and its relationship to classical sperm parameters and in vitro fertilization-intracytoplasmic sperm injection outcome. AB - OBJECTIVE: To relate the glutathione peroxidase (GPX) activity level in human seminal plasma with standard semen parameters and spermatozoa fertilization potential in terms of fertilization and pregnancy rates in an IVF program. DESIGN: Prospective study. SETTING: Human Reproduction Unit at Cruces Hospital (Vizcaya, Spain). PATIENT(S): Three hundred consecutive males from infertile couples participating in the IVF program. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Analysis of GPX activity in seminal plasma by spectrophotometry. RESULT(S): GPX activity in seminal plasma was significantly lower in patients with abnormal sperm as assessed by 1999 and 2010 World Health Organization (WHO) criteria, compared with normozoospermic individuals. There was a more significant decrease in those samples with severe sperm pathologies. GPX values were significantly lower in samples with severe asthenozoospermia, oligozoospermia, and teratozoospermia compared with normal samples. However, there was no correlation between GPX activity in seminal plasma in IVF patients and fertilization rates or pregnancy outcome. CONCLUSION(S): Although seminal plasma GPX activity was related to semen quality according to WHO parameters, such an association was not found with IVF-intracytoplasmic sperm injection (ICSI) outcome, presumably because of the well-known ability of IVF-ICSI procedures to overcome sperm deficiencies in the fertilization process. PMID- 22296824 TI - Cadmium may affect newborn girls more than boys: maternal exposure linked to smaller birth size. PMID- 22296825 TI - The yeast mitogen-activated protein kinase Slt2 is involved in the cellular response to genotoxic stress. AB - BACKGROUND: The maintenance of genomic integrity is essential for cell viability. Complex signalling pathways (DNA integrity checkpoints) mediate the response to genotoxic stresses. Identifying new functions involved in the cellular response to DNA-damage is crucial. The Saccharomyces cerevisiae SLT2 gene encodes a member of the mitogen-activated protein kinase (MAPK) cascade whose main function is the maintenance of the cell wall integrity. However, different observations suggest that SLT2 may also have a role related to DNA metabolism. RESULTS: This work consisted in a comprehensive study to connect the Slt2 protein to genome integrity maintenance in response to genotoxic stresses. The slt2 mutant strain was hypersensitive to a variety of genotoxic treatments, including incubation with hydroxyurea (HU), methylmetanosulfonate (MMS), phleomycin or UV irradiation. Furthermore, Slt2 was activated by all these treatments, which suggests that Slt2 plays a central role in the cellular response to genotoxic stresses. Activation of Slt2 was not dependent on the DNA integrity checkpoint. For MMS and UV, Slt2 activation required progression through the cell cycle. In contrast, HU also activated Slt2 in nocodazol-arrested cells, which suggests that Slt2 may respond to dNTP pools alterations. However, neither the protein level of the distinct ribonucleotide reductase subunits nor the dNTP pools were affected in a slt2 mutant strain. An analysis of the checkpoint function revealed that Slt2 was not required for either cell cycle arrest or the activation of the Rad53 checkpoint kinase in response to DNA damage. However, slt2 mutant cells showed an elongated bud and partially impaired Swe1 degradation after replicative stress, indicating that Slt2 could contribute, in parallel with Rad53, to bud morphogenesis control after genotoxic stresses. CONCLUSIONS: Slt2 is activated by several genotoxic treatments and is required to properly cope with DNA damage. Slt2 function is important for bud morphogenesis and optimal Swe1 degradation under replicative stress. The MAPK Slt2 appears as a new player in the cellular response to genotoxic stresses. PMID- 22296826 TI - New active HIV-1 protease inhibitors derived from 3-hexanol: conformation study of the free inhibitors in crystalline state and in complex with the enzyme. AB - Four novel linear non-peptidic HIV-1 protease inhibitors derived from 2,5-diamino 1,6-diphenyl-3-hexanol were synthesized and characterized. All of them exhibit tight binding to HIV-1 protease, with inhibition constants K(i) in the range 20 pm-5 nm. The investigated inhibitors were crystallized, and their crystal structures were determined by X-ray diffraction. In all cases, the conformations found in the crystalline state differ significantly from the conformations obtained by computational docking of the inhibitor in the binding cleft of native HIV-1 protease. Owing to the prevalence of hydrophobic substituents in all these inhibitors, the conformational mobility in water solution is restricted to their compact forms. The spectrum of low-energy conformations in solution dramatically changes during the formation of inhibitor crystals (phenyl ring stacking as a leading motif) or during the formation of a complex with HIV-1 protease (elongated conformation suitable to fit the enzyme pockets as a factor responsible for tight binding). High conformational flexibility and low conformational stress in the molecules of these inhibitors most likely increase their biological activity in comparison with more rigid compounds. PMID- 22296827 TI - Tunicate cytostatic factor TC14-3 induces a polycomb group gene and histone modification through Ca(2+) binding and protein dimerization. AB - BACKGROUND: As many invertebrate species have multipotent cells that undergo cell growth and differentiation during regeneration and budding, many unique and interesting homeostatic factors are expected to exist in those animals. However, our understanding of such factors and global mechanisms remains very poor. Single zooids of the tunicate, Polyandrocarpa misakiensis, can give off as many as 40 buds during the life span. Bud development proceeds by means of transdifferentiation of very limited number of cells and tissues. TC14-3 is one of several different but closely related polypeptides isolated from P. misakiensis. It acts as a cytostatic factor that regulates proliferation, adhesion, and differentiation of multipotent cells, although the molecular mechanism remains uncertain. The Polycomb group (PcG) genes are involved in epigenetic control of genomic activity in mammals. In invertebrates except Drosophila, PcG and histone methylation have not been studied so extensively, and genome-wide gene regulation is poorly understood. RESULTS: When Phe(65) of TC14-3 was mutated to an acidic amino acid, the resultant mutant protein failed to dimerize. The replacement of Thr(69) with Arg(69) made dimers unstable. When Glu(106) was changed to Gly(106), the resultant mutant protein completely lost Ca(2+) binding. All these mutant proteins lacked cytostatic activity, indicating the requirement of protein dimerization and calcium for the activity. Polyandrocarpa Eed, a component of PcG, is highly expressed during budding, like TC14-3. When wild-type and mutant TC14-3s were applied in vivo and in vitro to Polyandrocarpa cells, only wild-type TC14-3 could induce Eed without affecting histone methyltransferase gene expression. Eed-expressing cells underwent trimethylation of histone H3 lysine27. PmEed knockdown by RNA interference rescued cultured cells from the growth-inhibitory effects of TC14-3. CONCLUSION: These results show that in P. misakiensis, the cytostatic activity of TC14-3 is mediated by PmEed and resultant histone modification, and that the gene expression requires both the protein dimerization and Ca(2+)-binding of TC14-3. This system consisting of a humoral factor, PcG, and histone methylation would contribute to the homeostatic regulation of cell growth and terminal differentiation of invertebrate multipotent cells. PMID- 22296828 TI - Improving yield by exploiting mechanisms underlying natural variation of photosynthesis. AB - Increasing photosynthesis in C3 species has been identified as an approach to increase the yield of crop plants. Most of our knowledge of photosynthetic performance has come from studies in which plants were grown in controlled growth conditions but plants in natural environments have to cope with unpredictable and rapidly changing conditions. Plants adapt to the light environment in which they grow and this is demonstrated by the differences in anatomy and morphology of leaves in sun and shade leaves. Superimposed on this are the dynamic responses of plants to rapid changes in the light environment that occur throughout the day. Application of next generation sequencing (NGS), QTL analysis and innovative phenomic screening can provide information to underpin approaches for breeding of higher yielding crop plants. PMID- 22296829 TI - Antitumor immunologically modified carbon nanotubes for photothermal therapy. AB - An immunologically modified nanotube system was developed using an immunoadjuvant, glycated chitosan (GC), as surfactant of single-walled carbon nanotube (SWNTs). This SWNT-GC system not only retained both optical properties of SWNTs and immunological functions of GC, but also could enter cells due to the carrier properties of SWNTs. Cellular SWNTs induced thermal destruction of tumor cells when irradiated by a near-infrared laser and, at the same time, cellular GC could serve both as damage associated molecular pattern molecules (DAMPs) and pathogen associated molecular pattern molecules (PAMPs) to enhance the tumor immunogenicity and enhance the uptake and presentation of tumor antigens, leading to special antitumor response. Using this system and a 980 nm laser, we treated tumors, both in vitro and in vivo, and investigated the induced thermal and immunological effects. Laser + SWNT-GC afford a remarkable efficacy in suppressing tumor growth in animal cancer models, in many cases resulting in complete tumor regression and long-term survival. Mice successfully treated by Laser + SWNT-GC could establish resistance to tumor rechallenge. This system forms a multifunctional temporal-spatial continuum, which can synergize photothermal and immunological effects. The Laser + SWNT-GC could represent a promising treatment modality to induce systemic antitumor response through a local intervention, while minimizing the adverse side effects. PMID- 22296830 TI - Methodologies used in cost-effectiveness models for evaluating treatments in major depressive disorder: a systematic review. AB - BACKGROUND: Decision makers in many jurisdictions use cost-effectiveness estimates as an aid for selecting interventions with an appropriate balance between health benefits and costs. This systematic literature review aims to provide an overview of published cost-effectiveness models in major depressive disorder (MDD) with a focus on the methods employed. Key components of the identified models are discussed and any challenges in developing models are highlighted. METHODS: A systematic literature search was performed to identify all primary model-based economic evaluations of MDD interventions indexed in MEDLINE, the Cochrane Library, EMBASE, EconLit, and PsycINFO between January 2000 and May 2010. RESULTS: A total of 37 studies were included in the review. These studies predominantly evaluated antidepressant medications. The analyses were performed across a broad set of countries. The majority of models were decision trees; eight were Markov models. Most models had a time horizon of less than 1 year. The majority of analyses took a payer perspective. Clinical input data were obtained from pooled placebo-controlled comparative trials, single head-to-head trials, or meta-analyses. The majority of studies (24 of 37) used treatment success or symptom-free days as main outcomes, 14 studies incorporated health state utilities, and 2 used disability-adjusted life-years. A few models (14 of 37) incorporated probabilities and costs associated with suicide and/or suicide attempts. Two models examined the cost-effectiveness of second-line treatment in patients who had failed to respond to initial therapy. Resource use data used in the models were obtained mostly from expert opinion. All studies, with the exception of one, explored parameter uncertainty. CONCLUSIONS: The review identified several model input data gaps, including utility values in partial responders, efficacy of second-line treatments, and resource utilisation estimates obtained from relevant, high-quality studies. It highlighted the differences in outcome measures among the trials of MDD interventions, which can lead to difficulty in performing indirect comparisons, and the inconsistencies in definitions of health states used in the clinical trials and those used in utility studies. Clinical outcomes contributed to the uncertainty in cost effectiveness estimates to a greater degree than costs or utility weights. PMID- 22296831 TI - [Management of limb lymphedema]. AB - Lymphedema results from impaired lymphatic transport with increased limb volume. Cellulitis is the main complication, but psychological or functional discomfort may occur throughout the course of lymphedema. Lymphedema management is based on complete decongestive physiotherapy (multilayer low stretch bandage, manual lymph drainage, skin care, exercises). First phase of treatment leads to a reduction of lymphedema volume. The second phase stabilizes the volume and is based on elastic compression. Resection surgery is a useful tool in external genitalia lymphedema. PMID- 22296832 TI - In vivo analysis of conjunctiva in canaloplasty for glaucoma. AB - AIM: To assess the epithelial features of the bulbar conjunctiva using in vivo confocal microscopy in patients with glaucoma undergoing canaloplasty. METHODS: Thirty consecutive patients with glaucoma were enrolled. Canaloplasty was considered successful if the preoperative intraocular pressure (IOP) was reduced by one-third. The conjunctiva was examined using confocal laser-scanning microscopy 1 week before (baseline) and 12 weeks after surgery. The mean density (MMD, cysts/mm(2)) and mean area (MMA, MUm(2)) of conjunctival microcysts and IOP were measured. Anterior segment optical coherence tomography was performed to evaluate post-operative trabecular distension and scleral modifications at the surgery site. RESULTS: Twelve weeks after surgery, canaloplasty was successful in 23 patients (group 1) but unsuccessful in 7 (group 2). At baseline, IOP was 28.1+/-2.98 and 28.3+/-2.81 mm Hg, MMD was 10.61+/-4.31 and 11.35+/-5.6 and MMA was 2845.02+/-411.85 and 2700.56+/-518.85 in groups 1 and 2, respectively (p>0.05). Twelve weeks after canaloplasty, mean IOP was 13.2+/-4.48 (p<0.05) and 24.6+/-3.48 mm Hg in groups 1 and 2, respectively. In group 1, MMD and MMA were 37.86+/-21.4 and 11997.84+/-8630.35, respectively, a fourfold increase compared to baseline (p<0.001); no significant differences were found in group 2. Conjunctival bleb was not documented in any case. CONCLUSIONS: Conjunctival microcysts were evident in all glaucomatous eyes prior to surgery, and tended to increase in density and surface area after successful canaloplasty. These findings indicated enhanced aqueous humour filtration across the sclera and conjunctiva after canaloplasty. PMID- 22296833 TI - Visual improvement after corneal endothelial transplantation: are we seeing better? PMID- 22296834 TI - Myosin I links PIP3 signaling to remodeling of the actin cytoskeleton in chemotaxis. AB - Class I myosins participate in various interactions between the cell membrane and the cytoskeleton. Several class I myosins preferentially bind to acidic phospholipids, such as phosphatidylserine and phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2], through a tail homology 1 (TH1) domain. Here, we show that the second messenger lipid phosphatidylinositol 3,4,5-trisphosphate (PIP3) binds to the TH1 domain of a subset of Dictyostelium class I myosins (ID, IE, and IF) and recruits them to the plasma membrane. The PIP3-regulated membrane recruitment of myosin I promoted chemotaxis and induced chemoattractant stimulated actin polymerization. Similarly, PIP3 recruited human myosin IF to the plasma membrane upon chemotactic stimulation in a neutrophil cell line. These data suggest a mechanism through which the PIP3 signal is transmitted through myosin I to the actin cytoskeleton. PMID- 22296835 TI - PAS kinase promotes cell survival and growth through activation of Rho1. AB - In Saccharomyces cerevisiae, phosphorylation of Ugp1 by either of the yeast PASK family protein kinases (yPASK), Psk1 or Psk2, directs this metabolic enzyme to deliver glucose to the periphery for synthesis of the cell wall. However, we isolated PSK1 and PSK2 in a high-copy suppressor screen of a temperature sensitive mutant of target of rapamycin 2 (TOR2). Posttranslational activation of yPASK, either by cell integrity stress or by growth on nonfermentative carbon sources, also suppressed the growth defect resulting from tor2 mutation. Although suppression of the tor2 mutant growth phenotype by activation of the kinase activity of yPASK required phosphorylation of the metabolic enzyme Ugp1 on serine 11, this resulted in the formation of a complex that induced Rho1 activation, rather than required the glucose partitioning function of Ugp1. In addition to phosphorylated Ugp1, this complex contained Rom2, a Rho1 guanine nucleotide exchange factor, and Ssd1, an mRNA-binding protein. Activation of yPASK-dependent Ugp1 phosphorylation, therefore, enables two processes that are required for cell growth and stress resistance: synthesis of the cell wall through partitioning glucose to the periphery and the formation of the signaling complex with Rom2 and Ssd1 to promote Rho1-dependent polarized cell growth. This complex may integrate metabolic and signaling responses required for cell growth and survival in suboptimal conditions. PMID- 22296836 TI - Inequalities in cervical cancer screening for women with or without a regular consulting in primary care for gynaecological health, in Paris, France. AB - OBJECTIVES: To describe the individual characteristics associated with the absence of cervical smear (CCST); to investigate the role of residential neighbourhood, particularly practitioner density; and to explore changes in individual and contextual determinants after taking regular consulting in primary care for gynaecological health (RCGH) into account. METHODS: DATA: 1843 adult women from the SIRS survey conducted in 2005 in the Paris metropolitan area. Multilevel logistic regressions analysed factors associated with never-screening. RESULTS: 10% of the women had never undergone CCST. Being single, less educated, of foreign origin, with no children, and without health insurance, having never worked, having never undergone a serious health problem and/or having nobody in their circle with cancer were associated with no CCST. Once adjusted on individual characteristics, living in a middle- (OR=1.95; IC=1.05-3.62) or in a lower-class neighbourhood (OR=2.31; IC=1.26-4.25) was associated with increased risks of never-screening, but neighbourhood physician density was not. Interactions were found between socioeconomic status and RCGH. Individual- and neighbourhood-level associations with CCST were different for women with or without an RCGH. CONCLUSION: This study analysed individual and contextual inequalities in CCST practice in the Paris metropolitan area. To benefit from an RCGH did not seem to reduce all the social inequalities in CCST practice. PMID- 22296837 TI - The development of simple survival prediction models for blunt trauma victims treated at Asian emergency centers. AB - BACKGROUND: For real-time assessment of the probability of survival (Ps) of blunt trauma victims at emergency centers, this study aimed to establish regression models for estimating Ps using simplified coefficients. METHODS: The data of 10,210 blunt trauma patients not missing both the binary outcome data about survival and the data necessary for Ps calculation by The Trauma and Injury Severity Score (TRISS) method were extracted from the Japan Trauma Data Bank (2004-2007) and analyzed. Half (5,113) of the data was allocated to a derivation data set, with the other half (5,097) allocated to a validation data set. The data of 6,407 blunt trauma victims from the trauma registry of Khon Kaen Regional Hospital in Thailand were analyzed for validation. The logistic regression models included age, the Injury Severity Score (ISS), the Glasgow Coma Scale score (GCS), systolic blood pressure (SBP), respiratory rate (RR), and their coded values (cAGE, 0-1; cISS, 0-4; cSBP, 0-4; cGCS, 0-4; cRR, 0-4) as predictor variables. The coefficients were simplified by rounding off after the decimal point or choosing 0.5 if the coefficients varied across 0.5. The area under the receiver-operating characteristic curve (AUROCC) was calculated for each model to measure discriminant ability. RESULTS: A group of formulas (log (Ps/1-Ps) = logit (Ps) = -9 + cISS - cAGE + cSBP + cGCS + cRR/2, where -9 becomes -7 if the predictor variable of cRR or cISS is missing) was developed. Using these formulas, the AUROCCs were between 0.950 and 0.964. When these models were applied to the Khon Kean data, their AUROCCs were greater than 0.91. CONCLUSION: These equations allow physicians to perform real-time assessments of survival by easy mental calculations at Asian emergency centers, which are overcrowded with blunt injury victims of traffic accidents. PMID- 22296838 TI - AM fungi root colonization increases the production of essential isoprenoids vs. nonessential isoprenoids especially under drought stress conditions or after jasmonic acid application. AB - Previous studies have shown that root colonization by arbuscular mycorrhiza (AM) fungi enhances plant resistance to abiotic and biotic stressors and finally plant growth. However, little is known about the effect of AM on isoprenoid foliar and root content. In this study we tested whether the AM symbiosis affects carbon resource allocation to different classes of isoprenoids such as the volatile nonessential isoprenoids (monoterpenes and sesquiterpenes) and the non-volatile essential isoprenoids (abscisic acid, chlorophylls and carotenoids). By subjecting the plants to stressors such as drought and to exogenous application of JA, we wanted to test their interaction with AM symbiosis in conditions where isoprenoids usually play a role in resistance to stress and in plant defence. Root colonization by AM fungi favoured the leaf production of essential isoprenoids rather than nonessential ones, especially under drought stress conditions or after JA application. The increased carbon demand brought on by AM fungi might thus influence not only the amount of carbon allocated to isoprenoids, but also the carbon partitioning between the different classes of isoprenoids, thus explaining the not previously shown decrease of root volatile isoprenoids in AM plants. We propose that since AM fungi are a nutrient source for the plant, other carbon sinks normally necessary to increase nutrient uptake can be avoided and therefore the plant can devote more resources to synthesize essential isoprenoids for plant growth. PMID- 22296839 TI - sLORETA-qm for interictal MEG epileptic spike analysis: comparison of location and quantity with equivalent dipole estimation. AB - OBJECTIVE: To determine whether quantitative modification of a standardised low resolution brain electromagnetic tomography (sLORETA-qm) could be used as a reliable tool for quantitative analysis of magnetoencephalography (MEG) for analysis of the interictal epileptic spike. To verify the performance of sLORETA qm, magnetic source location and quantity were compared with the equivalent current dipole (ECD) method. METHODS: A total of 50 sources from 10 patients with epilepsy were obtained. Analyses were performed after the MEG data were 3-70 Hz band-pass filtered. Time points for analysis were selected referring to waveform patterns and the isofield contour map. With the same spherical model, source estimation was conducted with two methods of analysis: ECD and sLORETA-qm. Distance from the centre of the spherical model and intensities were compared between the methods. RESULTS: There were no significant differences between the methods in the distance from the spherical model (paired t-test, p=0.8761). Source intensities between the methods were strongly correlated (Spearman's Rho=0.9803, p<0.001). CONCLUSIONS: sLORETA-qm was closely correlated with ECD concerning point source location and quantity in analysis of the interictal epileptic spike. SIGNIFICANCE: sLORETA-qm is a reliable quantifiable method without arbitrariness for analysis of the interictal epileptic spike. PMID- 22296840 TI - Bioaccessibility of Se, Cu, Zn, Mn and Fe, and heme iron content in unaged and aged meat of Hereford and Braford steers fed pasture. AB - The content and the bioaccessibility of Se, Cu, Zn, Mn, and Fe were determined in unaged and aged meat (14days) from the Psoas major (PM), Gluteus medius (GM) and Longissimus dorsi (LD) muscles of Hereford (H) and Braford breed (B) steers fed pasture. Furthermore, the content of heme-Fe was determined in the same muscles. The H had a lower content of Cu and a higher content of Fe. Also, H had more heme Fe than B. The bioaccessibility in unaged meat for Se, Cu, Zn, Mn and Fe ranged between 75 and 91%, 30 and 45%, 40 and 68%, 55 and 95%, and 60 and 70%, respectively. After aging, the bioaccessibility for the same minerals ranged between 58 and 80%, 30 and 48%, 40 and 58%, 75 and 95%, and 59 and 70%, respectively. Aging affected negatively the Se content and its bioaccessibility, in the two breeds. Also, the heme-Fe content was negatively affected by aging in all muscles and breeds. PMID- 22296841 TI - Irritable bowel syndrome. AB - INTRODUCTION: The prevalence of irritable bowel syndrome (IBS) varies depending on the criteria used to diagnose it, but it ranges from about 5% to 20%. IBS is associated with abnormal gastrointestinal motor function and enhanced visceral perception, as well as psychosocial and genetic factors. People with IBS often have other bodily and psychiatric symptoms, and have an increased likelihood of having unnecessary surgery compared with people without IBS. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in people with IBS? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 27 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: 5HT(3) receptor antagonists (alosetron and ramosetron), 5HT(4) receptor agonists (tegaserod), antidepressants (tricyclic antidepressants and selective serotonin reuptake inhibitors [SSRIs]), antispasmodics (including peppermint oil), cognitive behavioural therapy (CBT), hypnotherapy, loperamide, and soluble and insoluble fibre supplementation. PMID- 22296842 TI - Matched comparison of rotational stability of 1-piece acrylic and plate-haptic silicone toric intraocular lenses in Asian eyes. AB - PURPOSE: To evaluate and compare the postoperative rotational stability of a 1 piece acrylic toric intraocular lens (IOL) (Acrysof) and a plate-haptic silicone toric IOL (Staar) in Asian eyes. SETTING: Singapore National Eye Centre, Singapore. DESIGN: Prospective randomized control trial. METHODS: Eyes of Chinese patients having cataract surgery were randomized to receive the acrylic toric IOL or the silicone toric IOL. Postoperatively, patients returned at 1 day, 1 week, and 1 and 3 months. The eyes were dilated and slitlamp retroillumination photography of the toric IOL was performed to assess rotational stability. RESULTS: The acrylic IOL was implanted in 24 eyes and the silicone IOL in 26 eyes. The mean age of the patients was 68.2 years (range 42 to 82 years). The mean IOL rotation from baseline to 3 months postoperatively was 4.23 +/- 4.28 degrees in the acrylic IOL group and 9.42 +/- 7.80 degrees in the silicone IOL group; the difference was statistically significant (P=.01). Of the acrylic IOLs, 73% were rotated less than 5 degrees at 3 months; none was rotated more than 15 degrees at 3 months. The silicone toric IOLs showed greater rotational movement, with 37% being rotated less than 5 degrees and 21% being rotated more than 15 degrees. CONCLUSION: The acrylic toric IOL had better rotational stability than the silicone toric IOL. PMID- 22296843 TI - Combined Descemet-stripping automated endothelial keratoplasty and phacoemulsification with toric intraocular lens implantation for treatment of failed penetrating keratoplasty with high regular astigmatism. AB - We present the case of a 57-year-old woman who had combined Descemet-stripping automated endothelial keratoplasty (DSAEK) and phacoemulsification with implantation of a toric intraocular lens (IOL). Surgery was intended to treat a cataract developing in a post-penetrating keratoplasty (PKP) eye with high astigmatism and endothelial decompensation. Six months after uneventful surgery, the cornea was clear and the corrected distance visual acuity was 20/20 with a refraction of +0.25 -1.00 * 10 (from -3.00 -8.50 * 12 preoperatively). The internal topography map (OPD-Scan) showed an IOL rotation of 4 degrees. The endothelial cell loss was 15% of the eye-bank value. Descemet-stripping automated endothelial keratoplasty combined with phacoemulsification and toric IOL implantation is a relatively simple and very effective procedure for eyes with endothelial failure and high post-PKP astigmatism. The speed of visual rehabilitation and final visual acuity achieved with this approach was superior to that obtained with other surgical procedures. PMID- 22296844 TI - Bilateral delayed nonpupillary block angle closure after insertion of phakic intraocular lens. PMID- 22296845 TI - Canadian guidelines for rhinosinusitis: practical tools for the busy clinician. AB - Acute bacterial rhinosinusitis (ABRS) and chronic rhinosinusitis (CRS) frequently present in clinical practice. Guidelines for management of these conditions have been published extensively in the past. However, a set of guidelines that addressed issues specific to the Canadian environment while offering clear guidance for first-line clinicians was needed, and resulted in the recent publication of Canadian clinical practice guidelines for ABRS and CRS. In addition to addressing issues specific to Canadian physicians, the presented guidelines are applicable internationally, and offer single algorithms for the diagnosis and management of ABRS and CRS, as well as expert opinion in areas that do not have an extensive evidence base. This commentary presents major points from the guidelines, as well as the intended impact of the guidelines on clinical practice.See guidelines at: http://www.aacijournal.com/content/7/1/2. PMID- 22296846 TI - Molecular mechanism underlying the regulatory specificity of a Drosophila homeodomain protein that specifies myoblast identity. AB - A subfamily of Drosophila homeodomain (HD) transcription factors (TFs) controls the identities of individual muscle founder cells (FCs). However, the molecular mechanisms by which these TFs generate unique FC genetic programs remain unknown. To investigate this problem, we first applied genome-wide mRNA expression profiling to identify genes that are activated or repressed by the muscle HD TFs Slouch (Slou) and Muscle segment homeobox (Msh). Next, we used protein-binding microarrays to define the sequences that are bound by Slou, Msh and other HD TFs that have mesodermal expression. These studies revealed that a large class of HDs, including Slou and Msh, predominantly recognize TAAT core sequences but that each HD also binds to unique sites that deviate from this canonical motif. To understand better the regulatory specificity of an individual FC identity HD, we evaluated the functions of atypical binding sites that are preferentially bound by Slou relative to other HDs within muscle enhancers that are either activated or repressed by this TF. These studies showed that Slou regulates the activities of particular myoblast enhancers through Slou-preferred sequences, whereas swapping these sequences for sites that are capable of binding to multiple HD family members does not support the normal regulatory functions of Slou. Moreover, atypical Slou-binding sites are overrepresented in putative enhancers associated with additional Slou-responsive FC genes. Collectively, these studies provide new insights into the roles of individual HD TFs in determining cellular identity, and suggest that the diversity of HD binding preferences can confer regulatory specificity. PMID- 22296847 TI - The metalloproteinase inhibitor Reck is essential for zebrafish DRG development. AB - The neural crest is a migratory, multipotent cell lineage that contributes to myriad tissues, including sensory neurons and glia of the dorsal root ganglia (DRG). To identify genes affecting cell fate specification in neural crest, we performed a forward genetic screen for mutations causing DRG deficiencies in zebrafish. This screen yielded a mutant lacking all DRG, which we named sensory deprived (sdp). We identified a total of four alleles of sdp, all of which possess lesions in the gene coding for reversion-inducing cysteine-rich protein containing Kazal motifs (Reck). Reck is an inhibitor of metalloproteinases previously shown to regulate cell motility. We found reck function to be both necessary for DRG formation and sufficient to rescue the sdp phenotype. reck is expressed in neural crest cells and is required in a cell-autonomous fashion for appropriate sensory neuron formation. In the absence of reck function, sensory neuron precursors fail to migrate to the position of the DRG, suggesting that this molecule is crucial for proper migration and differentiation. PMID- 22296848 TI - ETTIN (ARF3) physically interacts with KANADI proteins to form a functional complex essential for integument development and polarity determination in Arabidopsis. AB - KANADI (KAN) transcription factors promote abaxial cell fate throughout plant development and are required for organ formation during embryo, leaf, carpel and ovule development. ABERRANT TESTA SHAPE (ATS, or KAN4) is necessary during ovule development to maintain the boundary between the two ovule integuments and to promote inner integument growth. Yeast two-hybrid assays identified ETTIN (ETT, or AUXIN RESPONSE FACTOR 3) as a transcription factor that could physically interact with ATS. ATS and ETT were shown to physically interact in vivo in transiently transformed tobacco epidermal cells using bimolecular fluorescence complementation. ATS and ETT were found to share an overlapping expression pattern during Arabidopsis ovule development and loss of either gene resulted in congenital fusion of the integuments and altered seed morphology. We hypothesize that in wild-type ovules a physical interaction between ATS and ETT allows these proteins to act in concert to define the boundary between integument primordia. We further show protein-protein interaction in yeast between ETT and KAN1, a paralog of ATS. Thus, a direct physical association between ETT and KAN proteins underpins their previously described common role in polarity establishment and organogenesis. We propose that ETT-KAN protein complex(es) constitute part of an auxin-dependent regulatory module that plays a conserved role in a variety of developmental contexts. PMID- 22296849 TI - Stereotactic body radiation therapy for liver tumours using flattening filter free beam: dosimetric and technical considerations. AB - PURPOSE: To report the initial institute experience in terms of dosimetric and technical aspects in stereotactic body radiation therapy (SBRT) delivered using flattening filter free (FFF) beam in patients with liver lesions. METHODS AND MATERIALS: From October 2010 to September 2011, 55 consecutive patients with 73 primary or metastatic hepatic lesions were treated with SBRT on TrueBeam using FFF beam and RapidArc technique. Clinical target volume (CTV) was defined on multi-phase CT scans, PET/CT, MRI, and 4D-CT. Dose prescription was 75 Gy in 3 fractions to planning target volume (PTV). Constraints for organs at risk were: 700 cc of liver free from the 15 Gy isodose, Dmax < 21 Gy for stomach and duodenum, Dmax < 30 Gy for heart, D0.1 cc < 18 Gy for spinal cord, V15 Gy < 35% for kidneys. The dose was downscaled in cases of not full achievement of dose constraints. Daily cone beam CT (CBCT) was performed. RESULTS: Forty-three patients with a single lesion, nine with two lesions and three with three lesions were treated with this protocol. Target and organs at risk objectives were met for all patients. Mean delivery time was 2.8 +/- 1.0 min. Pre-treatment plan verification resulted in a Gamma Agreement Index of 98.6 +/- 0.8%. Mean on-line co-registration shift of the daily CBCT to the simulation CT were: -0.08, 0.05 and -0.02 cm with standard deviations of 0.33, 0.39 and 0.55 cm in, vertical, longitudinal and lateral directions respectively. CONCLUSIONS: SBRT for liver targets delivered by means of FFF resulted to be feasible with short beam on time. PMID- 22296850 TI - Genome-wide analysis of hepatic LRH-1 reveals a promoter binding preference and suggests a role in regulating genes of lipid metabolism in concert with FXR. AB - BACKGROUND: In a previous genome-wide analysis of FXR binding to hepatic chromatin, we noticed that an extra nuclear receptor (NR) half-site was co enriched close to the FXR binding IR-1 elements and we provided limited support that the monomeric LRH-1 receptor that binds to NR half-sites might function together with FXR to activate gene expression. RESULTS: To analyze the global pattern for LRH-1 binding and to determine whether it might associate with FXR on a whole genome-wide scale, we analyzed LRH-1 binding to the entire hepatic genome using a non-biased genome-wide ChIP-seq approach. We identified over 10,600 LRH-1 binding sites in hepatic chromatin and over 20% were located within 2 kb of the 5' end of a known mouse gene. Additionally, the results demonstrate that a significant fraction of the genome sites occupied by LRH-1 are located close to FXR binding sites revealed in our earlier study. A Gene ontology analysis revealed that genes preferentially enriched in the LRH-1/FXR overlapping gene set are related to lipid metabolism. These results demonstrate that LRH-1 recruits FXR to lipid metabolic genes. A significant fraction of FXR binding peaks also contain a nuclear receptor half-site that does not bind LRH-1 suggesting that additional monomeric nuclear receptors such as RORs and NR4As family members may also target FXR to other pathway selective genes related to other areas of metabolism such as glucose metabolism where FXR has also been shown to play an important role. CONCLUSION: These results document an important role for LRH-1 in hepatic metabolism through acting predominantly at proximal promoter sites and working in concert with additional nuclear receptors that bind to neighboring sites. PMID- 22296851 TI - De-hospitalization of the pediatric day surgery by means of a freestanding surgery center: pilot study in the Lazio Region. AB - BACKGROUND: Day surgery should take place in appropriate organizational settings. In the presence of high volumes, the organizational models of the Lazio Region are represented by either Day Surgery Units within continuous-cycle hospitals or day-cycle Day Surgery Centers. This pilot study presents the regional volumes provided in 2010 and the additional volumes that could be provided based on the best performance criterion with a view to suggesting the setting up of a regional Freestanding Center of Pediatric Day Surgery. METHODS: This is an observational retrospective study. The activity volumes have been assessed by means of a DRG (Diagnosis Related Group)-specific indicator that measures the ratio of outpatients to the total number of treated patients (freestanding indicator, FI). The included DRGs had an FI exceeding the 3rd quartile present in at least a health-care facility and a volume exceeding 0.5% of the total patients of the pediatric surgery and urology facilities of the Lazio Region. The relevant data have been provided by the Public Health Agency and relate to 2010. The best performance FI has been used to calculate the theoretical volume of transferability of the remaining facilities into freestanding surgery centers. Patients under six months of age and DRGs common to other disciplines have been excluded. The Chi Square test has been used to compare the FI of the health-care facilities and the FI of the places of origin of the patients. RESULTS: The DRG provided in 2010 amounted to a total of 5768 belonging to 121 types of procedures. The application of the criteria of inclusion have led to the selection of seven final DRG categories of minor surgery amounting to 3522 cases. Out of this total number, there were 2828 outpatients and 694 inpatients. The recourse of the best performance determines a potential transfer of 497 cases. The total outpatient volume is 57%. The Chi Square test has pointed to a statistically significant difference of the facilities and to a non-significant difference of inferiority of the regional places of origin with respect to the city of Rome. CONCLUSIONS: The activity volumes would seem to support the setting up of a Freestanding Regional Center of Pediatric Day Surgery. This Center represents the healthcare facility that is most likely to allow a de hospitalization process. Subsequent studies will be required to confirm the validity of this pilot study. PMID- 22296852 TI - Charcot foot: skin temperature as a good clinical parameter for predicting disease outcome. AB - Twenty-eight diabetics presenting with acute Charcot foot were immobilized and the temperature difference between limbs measured at each month. All patients had monthly follow-up visits for a year and the relapse rate was zero. We found that skin temperature is a good parameter to ensure safe immobilization withdrawal. PMID- 22296853 TI - Self-reported hypoglycemia and impact on quality of life and depression among adults with type 2 diabetes mellitus. AB - AIMS: This study evaluated the rate of self-reported hypoglycemia and examined the association of hypoglycemia with quality of life and depression among adults with type 2 diabetes mellitus (T2DM). METHODS: Respondents to the 2008 US Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD) survey were asked the number of times they experienced hypoglycemia in the past 4 weeks and past 12 months. Respondents also completed the short form-12 (SF-12) questionnaire and the patient health questionnaire (PHQ 9). T2DM respondents reporting at least 1 hypoglycemic episode were compared with T2DM respondents who did not report hypoglycemia in the previous 12 months. RESULTS: Of 2718 T2DM respondents, 23% reported experiencing hypoglycemia in the past 12 months. Respondents reporting hypoglycemia (n=627) had significantly lower (p<0.001) SF-12 scores for both physical health (mean+/-SD: 37.4+/-12.7 versus 40.9+/-12.7) and mental health (50.1+/-11.7 versus 52.4+/-10.1) compared with those without hypoglycemia (n=2091). Mean PHQ-9 scores were significantly higher (p<0.001) among respondents reporting hypoglycemia (5.2+/-5.8), compared with respondents who did not report hypoglycemia (3.9+/-5.0), indicating greater depression burden. CONCLUSION: Self-reported hypoglycemia was prevalent among individuals with T2DM and associated with lower health-related quality of life, and greater burden of depression. PMID- 22296854 TI - Effect of percutaneous electrical muscle stimulation on postprandial hyperglycemia in type 2 diabetes. AB - AIMS: The aim of this study was to examine whether percutaneous electrical muscle stimulation (EMS) attenuates postprandial hyperglycemia in type 2 diabetes. METHODS: Eleven patients with type 2 diabetes participated in two experimental sessions; one was a 30-min EMS 30 min after a breakfast (EMS trial) and the other was a complete rest after a breakfast (Control trial). In each trial, blood was sampled before and at 30, 60, 90, and 120 min after the meal. RESULTS: Postprandial glucose level was significantly attenuated in EMS trial at 60, 90, and 120 min after a meal (p<0.05). The C-peptide concentration was also significantly lowered in EMS trial (p<0.01). On the other hand, there was no significant increase in creatine phosphokinase (CPK) concentration in each trial. CONCLUSIONS: The present results provide first evidence indicating that EMS is a new exercise method for treating postprandial hyperglycemia in individuals with type 2 diabetes, especially who cannot perform adequate voluntary exercise because of excessive obesity, orthopedic diseases, or severe diabetic complications. PMID- 22296855 TI - Diabetes and life expectancy among Japanese - NIPPON DATA80. AB - Life expectancy (LE) among the Japanese population with or without diabetes mellitus was estimated. LE in 40-year old men and women was 41.1 and 47.5 years in those without diabetes and 32.3 and 40.9 years in those with diabetes. The LE of 40-year old men and women with diabetes was 8.8 and 6.6 years shorter than in those without diabetes. Diabetes mellitus leads to a decrease in LE. The presence of impaired glucose tolerance also affected LE inversely. PMID- 22296856 TI - Differential susceptibility of isolated human trophoblasts to infection by Trypanosoma cruzi. AB - The aim of the work was to analyze the susceptibility of the placental syncytiotrophoblast (STB) and cytotrophoblast (CTB) cells to infection by the causal agent of congenital Chagas' disease, Trypanosoma cruzi, and the possible parasite route for placental invasion. Monolayers of CTB and STB and VERO as control cells were used. The infection of STB was significantly lower that of the CTB and Vero cells (p < 0.05) which coincided with a significantly increased mortality of parasite cells in the culture medium and trypanocidal levels of nitric oxide. We conclude that the syncytiotrophoblast, the first placental barrier, is the main barrier of the chorionic villous that limits the infection by T. cruzi. This work opens the possibility of a new mechanism for placental infection when there are discontinuities in the first placental barrier. PMID- 22296857 TI - In the same boat? Health risks of water recreation are not limited to full contact activities. PMID- 22296858 TI - Comparative analysis of different DNA-binding drugs for leishmaniasis cure: a pharmacoinformatics approach. AB - Several experiments have been performed to test DNA-binding drugs to cure Leishmania infection. However, there are no details of pharmacoinformatics study. Herein, we have selected a good number of compounds from experimentally verified studies and performed a comparative analysis based on pharmacoinformatics techniques. In silico docking study was performed to observe the molecular level interactions of these known ligands with the DNA receptor by automated computational docking using Glide. A comparison between the calculated interaction energies and in silico ADME/T study was made. In agreement with drug likeness rules, our study suggests that seco-hydroxy-aza-CBI-TMI (compound 4b; GScore, -12.058) is a potential molecule for targeting the DNA to cure leishmaniasis. PMID- 22296859 TI - Characterization of a long-acting recombinant human serum albumin-atrial natriuretic factor (ANF) expressed in Pichia pastoris. AB - The cardiac hormone atrial natriuretic factor (ANF) combines pharmacological properties of drugs used to treat essential hypertension (EH), congestive heart failure (CHF) and acute myocardial infarction (AMI). Treatment of CHF or AMI patients with an intravenous (iv) infusion of the circulating form of ANF (ANF(99 126)) produces significant clinical improvement. The short half-life (5 min) and peptide nature of ANF impose logistic restrictions for chronic administration. To increase its half-life, we fused ANF and human serum albumin (HSA) mini-genes by recombination in Pichia pastoris. The activity of three configurations of the fusion protein was tested in vitro and in vivo. The fusion protein that comprised of C-terminus HSA connected to N-terminus ANF via a hexaglycine linker showed the best outcome; it increased cGMP production in vitro. In vivo an iv bolus of HSA ANF into mice increased significantly plasma cGMP levels and lowered blood pressure (BP) for up to 6 h hence successfully extended ANF half-life in plasma while retaining its biological activity. HSA-ANF represents the basis for development in the chronic therapeutic use of ANF. PMID- 22296860 TI - Late gadolinium enhancement cardiovascular magnetic resonance predicts clinical worsening in patients with pulmonary hypertension. AB - BACKGROUND: Late gadolinium enhancement (LGE) occurs at the right ventricular (RV) insertion point (RVIP) in patients with pulmonary hypertension (PH) and has been shown to correlate with cardiovascular magnetic resonance (CMR) derived RV indices. However, the prognostic role of RVIP-LGE and other CMR-derived parameters of RV function are not well established. Our aim was to evaluate the predictive value of contrast-enhanced CMR in patients with PH. METHODS: RV size, ejection fraction (RVEF), and the presence of RVIP-LGE were determined in 58 patients with PH referred for CMR. All patients underwent right heart catheterization, exercise testing, and N-terminal pro-brain natriuretic peptide (NT-proBNP) evaluation; results of which were included in the final analysis if performed within 4 months of the CMR study. Patients were followed for the primary endpoint of time to clinical worsening (death, decompensated right ventricular heart failure, initiation of prostacyclin, or lung transplantation). RESULTS: Overall, 40/58 (69%) of patients had RVIP-LGE. Patients with RVIP- LGE had larger right ventricular volume index, lower RVEF, and higher mean pulmonary artery pressure (mPAP), all p < 0.05. During the follow-up period of 10.2 +/- 6.3 months, 19 patients reached the primary endpoint. In a univariate analysis, RVIP LGE was a predictor for adverse outcomes (p = 0.026). In a multivariate analysis, CMR-derived RVEF was an independent predictor of clinical worsening (p = 0.036) along with well-established prognostic parameters such as exercise capacity (p = 0.010) and mPAP (p = 0.001). CONCLUSIONS: The presence of RVIP-LGE in patients with PH is a marker for more advanced disease and poor prognosis. In addition, this study reveals for the first time that CMR-derived RVEF is an independent non invasive imaging predictor of adverse outcomes in this patient population. PMID- 22296861 TI - Microvascular architecture of human epicolic and paracolic lymph nodes located in the vicinity of colon cancer: a SEM study of corrosion casts. AB - The vascular systems of epicolic and paracolic lymph nodes located in the vicinity of colon tumors resected from three patients were investigated by corrosion casting and scanning electron microscopy. Large vessels entered the nodes either at one site, not always corresponding with the anatomical hilus, or at 2-4 sites located along their perimeters. In the cortical zone of most examined nodes, the location of lymphoid nodules was marked by rosette-like capillary arrays drained by peripheral arcuate venules. The paracortex and medulla showed a dense capillary network with areas of tortuous capillaries, sometimes forming glomerular arrays suggesting nonsprouting angiogenesis by capillary elongation. Venules were abundant, especially in the paracortex and medulla, but high endothelial venules showing characteristic imprints of bulging endothelial cells in the casts were very rarely observed. Focal angiogenesis, abundance of venules and scarcity of high endothelial venules could result from remodeling of blood vessels induced by the tumor. PMID- 22296862 TI - Sclerosing mediastinitis and mast cell activation syndrome. AB - BACKGROUND: Sclerosing mediastinitis (ScM) is a rare, potentially life threatening disorder, idiopathic in roughly half the cases. Systemic symptoms not attributable to sclerosis often appear in idiopathic ScM. Mast cell activation disease (MCAD) is a potential cause of these symptoms and also can cause sclerosis. ScM has not previously been associated with MCAD. Presented here are the first two cases of ScM associated with MCAD, specifically mast cell activation syndrome (MCAS). CASE 1: A 58-year-old chronically polymorbid woman developed ScM following matched sibling allogeneic stem cell transplantation. Eight years later MCAS, likely underlying most of her chronic issues, was identified. CASE 2: A 30-year-old chronically polymorbid woman presented with superior vena cava syndrome and was diagnosed with ScM. On further evaluation, MCAS was identified. Treatment promptly effected symptomatic improvement; sclerosis has been stable. Non-compliance yielded symptomatic relapse; restored compliance re-achieved symptomatic remission. CONCLUSIONS: Different MCAS presentations reflect elaboration of different mediators, some of which can induce inflammation and fibrosis. Thus, MCAS may have directly and/or indirectly driven ScM in these patients. MCAS should be considered in ScM presenting with comorbidities better explained by mast cell mediator release. PMID- 22296863 TI - Betel quid use in relation to infectious disease outcomes in Cambodia. AB - OBJECTIVES: The habitual chewing of betel quid (areca nut, betel leaf, tobacco) is estimated to occur among 600 million persons in Asia and the Asia-Pacific Region. Emerging data from rural Asia indicate that the betel quid is part of traditional medicine practices that promote its use for a wide range of ailments, including infectious disease. In the present study, we examined the association between betel quid, traditional medicine, and infectious disease outcomes. METHODS: For the purpose of a nationwide, interviewer-administered, cross sectional survey of tobacco use (including betel quid), we conducted a stratified three-stage cluster sampling of 13 988 adults aged 18 years and older from all provinces of Cambodia. RESULTS: We found an association between the intensity of betel quid use and HIV/AIDS (odds ratio (OR) 2.06, 95% CI 1.09-3.89), dengue fever (OR 2.40, 95% CI 1.55-2.72), tuberculosis (OR 1.50, 95% CI 0.96-2.36), and typhoid (OR 1.48, 95% CI 0.95-2.30). These associations were even stronger in women - the primary users of betel quid in Cambodia. Multivariable analyses that controlled for age, gender, income, education, urban versus rural dwelling, receiving care from traditional medicine practitioners, and cigarette smoking did not alter the betel quid-infectious disease association. CONCLUSIONS: Our findings raise the possibility of a role of betel quid use in the transmission of infectious disease through pathways such as immunosuppression, oral route of entry for a pathogen (i.e., through injury to the oral mucosa), and contamination (i.e., fecal-oral) of the betel quid ingredients. PMID- 22296864 TI - Comparison of doxycycline-streptomycin, doxycycline-rifampin, and ofloxacin rifampin in the treatment of brucellosis: a randomized clinical trial. AB - BACKGROUND: Traditional regimens for the treatment of brucellosis are associated with significant relapse rates. The aim of this study was to compare the efficacy of ofloxacin plus rifampin (OFX-RIF) versus doxycycline plus streptomycin (DOX STR) and doxycycline plus rifampin (DOX-RIF) regimens in the treatment of brucellosis. METHODS: Two hundred and nineteen patients with brucellosis were enrolled in a randomized clinical trial; 28 cases were withdrawn because they did not attend the follow-up. Out of 191 patients with brucellosis, 64 received OFX RIF, 62 received DOX-RIF, and 65 patients received DOX-STR regimens. All patients were assessed during the period of therapy in the second, fourth, and sixth weeks by clinical course and were also followed up clinically and serologically for 6 months after the cessation of therapy. RESULTS: The highest clinical response (95.4%) was observed in the DOX-STR group (p=0.009). The results of multivariate analysis indicate that treatment with DOX-STR had the least therapeutic failures among the three groups (p=0.033). Adverse reactions were seen in 16.8% of patients, but there was no significant difference among the three groups (p=0.613). The lowest relapse rate (4.6%) was observed in the DOX-STR group (p=0.109). CONCLUSIONS: We conclude that the DOX-STR combination should remain the first-line regimen for the treatment of brucellosis in our region; we recommend DOX-RIF and OFX-RIF combinations as the second-line regimens. PMID- 22296865 TI - DHEA and cognition in HIV-positive patients with non-major depression. AB - BACKGROUND: Dihydroepiandrosterone (DHEA) has been investigated for its potential role in improving cognition in a number of patient populations. Treatment options are limited for HIV-associated neurocognitive disorders. OBJECTIVE: The authors tested the effect of DHEA administration on the cognitive functioning of HIV positive subjects with non-major depression. METHOD: The neuropsychological testing data for 60 HIV-positive patients enrolled in a clinical trial for non major depression were analyzed to determine if DHEA-treated patients demonstrated improved cognitive functioning versus placebo. RESULTS: At baseline, 80% of the sample met criteria for asymptomatic cognitive impairment. No benefit in cognitive performance was found on 16 of 17 neuropsychological measures evaluated. One measure showed a modest benefit for placebo-treated patients over DHEA. CONCLUSION: DHEA treatment was not associated with improved cognitive performance in HIV-positive patients with non-major depression. PMID- 22296866 TI - The comorbidity of self-reported chronic fatigue syndrome, post-traumatic stress disorder, and traumatic symptoms. AB - BACKGROUND: Data from primary care and community samples suggest higher rates of post-traumatic stress disorder (PTSD) among individuals with chronic fatigue syndrome (CFS). OBJECTIVE: This study investigated the co-occurrence of CFS, PTSD, and trauma symptoms and assessed the contribution of familial factors to the association of CFS with lifetime PTSD and current traumatic symptoms. METHOD: Data on lifetime CFS and PTSD, as measured by self-report of a doctor's diagnosis of the disorder, and standardized questionnaire data on traumatic symptoms, using the Impact of Events Scale (IES), were obtained from 8544 female and male twins from the community-based University of Washington Twin Registry. RESULTS: Lifetime prevalence of CFS was 2% and lifetime prevalence of PTSD was 4%. Participants who reported a history of PTSD were over eight times more likely to report a history of CFS. Participants with scores >= 26 on the IES were over four times more likely to report CFS than those who had scores <= 25. These associations were attenuated but remained significant after adjusting for familial factors through within-twin pair analyses. CONCLUSION: These results support similar findings that a lifetime diagnosis of CFS is strongly associated with both lifetime PTSD and current traumatic symptoms, although familial factors, such as shared genetic and environmental contributions, played a limited role in the relationship between CFS, PTSD, and traumatic symptoms. These findings suggest that future research should investigate both the familial and the unique environmental factors that may give rise to both CFS and PTSD. PMID- 22296867 TI - Changes in pain sensitivity following spinal manipulation: a systematic review and meta-analysis. AB - Spinal manipulation (SMT) is commonly used for treating individuals experiencing musculoskeletal pain. The mechanisms of SMT remain unclear; however, pain sensitivity testing may provide insight into these mechanisms. The purpose of this systematic review is to examine the literature on the hypoalgesic effects of SMT on pain sensitivity measures and to quantify these effects using meta analysis. We performed a systematic search of articles using CINAHL, MEDLINE, PsycINFO, and SPORTDiscus from each databases' inception until May 2011. We examined methodological quality of each study and generated pooled effect size estimates using meta-analysis software. Of 997 articles identified, 20 met inclusion criteria for this review. Pain sensitivity testing used in these studies included chemical, electrical, mechanical, and thermal stimuli applied to various anatomical locations. Meta-analysis was appropriate for studies examining the immediate effect of SMT on mechanical pressure pain threshold (PPT). SMT demonstrated a favorable effect over other interventions on increasing PPT. Subgroup analysis showed a significant effect of SMT on increasing PPT at the remote sites of stimulus application supporting a potential central nervous system mechanism. Future studies of SMT related hypoalgesia should include multiple experimental stimuli and test at multiple anatomical sites. PMID- 22296868 TI - Longitudinal evaluation of sEMG of masticatory muscles and kinematics of mandible changes in children treated for unilateral cross-bite. AB - The aim of this study was to evaluate masticatory muscle activity and kinematics of mandible changes in children with unilateral posterior cross-bite (UPXB) after orthodontic treatment, and one year after retention. Twenty-five children with UPXB and functional mandibular shift were evaluated before treatment (mean age 12.5years), after treatment (mean age 14.9years), and one year after retention (mean age 16.8years). The same data were collected in a control group of thirty age-matched normocclusive children. Simultaneous bilateral surface electromyographic (sEMG) activity from anterior temporalis (AT), posterior temporalis (PT), masseter (MA), and supra-hyoid (SH) muscle areas were evaluated at rest, during swallowing, mastication and clenching. Kinematic records of rest position, mandibular lateral shift, swallowing and mastication were analyzed. Results showed a lateral shift of the mandible present at rest. During swallowing, sEMG activity of SH predominated before and post-treatment and retention. High frequency of immature swallowing was maintained post-treatment and retention. During mastication, MA activity increased significantly and its asymmetry was corrected post-treatment. During clenching, cross-bite side AT and MA activity increased significantly posttreatment and remained stable after retention, and MA/AT ratio reversed. These findings reinforce the advantages of treating children with UPXB and functional shift as early as possible. PMID- 22296869 TI - Removing ECG contamination from EMG recordings: a comparison of ICA-based and other filtering procedures. AB - Trunk muscle electromyography (EMG) is often contaminated by the electrocardiogram (ECG), which hampers data analysis and potentially yields misinterpretations. We propose the use of independent component analysis (ICA) for removing ECG contamination and compared it with other procedures previously developed to decontaminate EMG. To mimic realistic contamination while having uncontaminated reference signals, we employed EMG recordings from peripheral muscles with different activation patterns and superimposed distinct ECG signals that were recorded during rest at conventional locations for trunk muscle EMG. ICA decomposition was performed with and without a separately collected ECG signal as part of the data set and contaminated ICA modes representing ECG were identified automatically. Root mean squared relative errors and correlations between the linear envelopes of uncontaminated and contaminated EMG were calculated to assess filtering effects on EMG amplitude. Changes in spectral content were quantified via mean power frequencies. ICA-based filtering largely preserved the EMG's spectral content. Performance on amplitude measures was especially successful when a separate ECG recording was included. That is, the ICA-based filtering can produce excellent results when EMG and ECG are indeed statistically independent and when mode selection is flexibly adjusted to the data set under study. PMID- 22296870 TI - Ammonium removal by Agrobacterium sp. LAD9 capable of heterotrophic nitrification aerobic denitrification. AB - Characteristics of ammonium removal by a newly isolated heterotrophic nitrification-aerobic denitrification bacterium Agrobacterium sp. LAD9 were systematically investigated. Succinate and acetate were found to be the most favorable carbon sources for LAD9. Response surface methodology (RSM) analysis demonstrated that maximum removal of ammonium occurred under the conditions with an initial pH of 8.46, C/N ratio of 8.28, temperature of 27.9 degrees C and shaking speed of 150rpm, where temperature and shaking speed produced the largest effect. Further nitrogen balance analysis revealed that 50.1% of nitrogen was removed as gas products and 40.8% was converted to the biomass. Moreover, the occurrence of aerobic denitrification was evidenced by the utilization of nitrite and nitrate as nitrogen sources, and the successful amplifications of membrane bound nitrate reductase and cytochrome cd(1) nitrite reductase genes from strain LAD9. Thus, the nitrogen removal in strain LAD9 was speculated to comply with the mechanism of heterotrophic nitrification coupled with aerobic denitrification (NH(4)(+)-NH(2)OH-NO(2)(-)-N(2)O-N(2)), in which also accompanied with the mutual transformation of nitrite and nitrate. The findings can help in applying appropriate controls over operational parameters in systems involving the use of this kind of strain. PMID- 22296871 TI - Body composition: why, when and for who? AB - Body composition reflects nutritional intakes, losses and needs over time. Undernutrition, i.e. fat-free mass (FFM) loss, is associated with decreased survival, worse clinical outcome and quality of life, as well as increased therapy toxicity in cancer patients. In numerous clinical situations, such as sarcopenic obesity and chronic diseases, the measurement of body composition with available methods, such as dual-X ray absorptiometry, computerized tomography and bioelectrical impedance analysis, quantifies the loss of FFM, whereas body weight loss and body mass index only inconstantly reflect FFM loss. The measurement of body composition allows documenting the efficiency of nutrition support, tailoring the choice of disease-specific and nutritional therapies and evaluating their efficacy and putative toxicity. Easy-to-use body composition methods integrated to the routine of care allow sequential measurements for an initial nutritional assessment and objective patients follow-up. By allowing an earlier and objective management of undernutrition, body composition assessment could contribute to reduce undernutrition-induced morbidity, worsening of quality of life, and global health care costs by a timely nutrition intervention. PMID- 22296872 TI - Sexual dimorphism modulates the impact of cancer cachexia on lower limb muscle mass and function. AB - BACKGROUND & AIMS: There is a sparsity of data on the impact of cachexia on human muscle function. This study examined the relationship between cachexia, quality of life and the mass/function/mechanical quality of lower limb skeletal muscle in gastrointestinal cancer patients. METHODS: Quadriceps strength and lower limb power were measured in 54 patients with gastrointestinal cancer (n = 24 >= 10% weight-loss) and 18 healthy controls. Quadriceps cross-sectional area was measured in 33/54 patients and in all controls using MRI. Muscle mechanical quality was defined as quadriceps strength/unit quadriceps cross-sectional area. Quality of life was assessed using the EORTC QLQ-C30. Patients with weight-loss >= 10% were classified as cachectic. RESULTS: In male cachectic patients, quadriceps strength (p = 0.003), lower limb power (p = 0.026), quadriceps cross sectional area (p = 0.019) and muscle quality (p = 0.008) were reduced compared with controls. In female cachectic patients, quadriceps strength (p = 0.001) and muscle quality (p = 0.001) were reduced compared with controls. Physical function (p = 0.013) and fatigue (p = 0.004) quality of life scores were reduced in male cachectic compared with non-cachectic patients, but not in females. CONCLUSIONS: Muscle quality is reduced in cancer patients. The degree of impairment of lower limb muscle mass, quality and function and the impact on quality of life varies with weight-loss and sex. PMID- 22296873 TI - Habitual salt intake and risk of gastric cancer: a meta-analysis of prospective studies. AB - BACKGROUND & AIMS: Systematic reviews of case-control studies evaluating the relationship between dietary salt intake and gastric cancer showed a positive association, however a quantitative analysis of longitudinal cohort studies is lacking. Therefore, we carried out a meta-analysis to assess the association between habitual salt intake and risk of gastric cancer in prospective studies. METHODS: We performed a systematic search of published articles (1966-2010). Criteria for inclusion were: original articles, prospective adult population studies, assessment of salt intake as baseline exposure and of gastric cancer as outcome, follow-up of at least 4 years, indication of number of participants exposed and events across different salt intake categories. RESULTS: Seven studies (10 cohorts) met the inclusion criteria (268 718 participants, 1474 events, follow-up 6-15 years). In the pooled analysis, "high" and "moderately high" vs "low" salt intake were both associated with increased risk of gastric cancer (RR = 1.68 [95% C.I. 1.17-2.41], p = 0.005 and respectively 1.41 [1.03 1.93], p = 0.032), with no evidence of publication bias. The association was stronger in the Japanese population and higher consumption of selected salt-rich foods was also associated with greater risk. Meta-regression analyses did not detect specific sources of heterogeneity. CONCLUSIONS: Dietary salt intake was directly associated with risk of gastric cancer in prospective population studies, with progressively increasing risk across consumption levels. PMID- 22296874 TI - Impact of a Health-At-Every-Size intervention on changes in dietary intakes and eating patterns in premenopausal overweight women: results of a randomized trial. AB - BACKGROUND & AIMS: Previous studies have shown improvements in eating behaviors following a Health-At-Every-Size approach (HAES). However, to our knowledge, no study has yet investigated how a HAES intervention could influence dietary intakes and eating patterns in overweight women. Therefore, objectives of this study were to determine changes in dietary intakes and eating patterns in premenopausal overweight women in response to a HAES intervention compared to a social support intervention and a control group, and then to determine whether changes in eating behaviors were associated with changes in dietary intakes and eating patterns in response to the HAES intervention. METHODS: Women completed a 3-day food record and the Three-Factor Eating Questionnaire was used to assess eating behaviors. RESULTS: Energy intake (main effect of time; p = 0.045) and snack frequency (main effect of time; p = 0.0004) decreased similarly over time in the three groups whereas proportion of energy intake from breakfast (main effect of time; p = 0.03) increased over time. Within HAES group, decreases in hunger and external hunger were associated with a decrease in total daily energy intake (r = 0.50, p = 0.0009 and r = 0.50, p = 0.0007, respectively). CONCLUSIONS: HAES intervention has no specific impact on eating patterns. However, a decrease in hunger, which characterizes women who respond well to HAES, is associated with a decrease in overall energy intake. Clinical trial registration number (www.clinicaltrials.gov): NCT01240499. PMID- 22296875 TI - Development and validation of serum bilirubin nomogram to predict the absence of risk for severe hyperbilirubinaemia before discharge: a prospective, multicenter study. AB - BACKGROUND: Early discharge of healthy late preterm and full term newborn infants has become common practice because of the current social and economic necessities. Severe jaundice, and even kernicterus, has developed in some term infants discharged early. This study was designed to elaborate a percentile-based hour specific total serum bilirubin (TSB) nomogram and to assess its ability to predict the absence of risk for subsequent non physiologic severe hyperbilirubinaemia before discharge. METHODS: A percentile-based hour-specific nomogram for TSB values was performed using TSB data of 1708 healthy full term neonates. The nomogram's predictive ability was then prospectively assessed in five different first level neonatal units, using a single TSB value determined before discharge. RESULTS: The 75 th percentile of hour specific TSB nomogram allows to predict newborn babies without significant hyperbilirubinemia only after the first 72 hours of life. In the first 48 hours of life the observation of false negative results did not permit a safe discharge from the hospital. CONCLUSION: The hour-specific TSB nomogram is able to predict all neonates without risk of non physiologic hyperbilirubinemia only after 48 to 72 hours of life. The combination of TSB determination and risk factors for hyperbilirubinemia could facilitate a safe discharge from the hospital and a targeted intervention and follow-up. PMID- 22296876 TI - Effect of aqueous extract of Arctium lappa L. (burdock) roots on the sexual behavior of male rats. AB - BACKGROUND: Arctium lappa L. root has traditionally been recommended as an aphrodisiac agent. It is used to treat impotence and sterility in China, and Native Americans included the root in herbal preparations for women in labor. However, its use has not been scientifically validated. The present study therefore investigated the effects of aqueous extract of Arctium lappa L. roots on sexual behavior in normal male rats. METHODS: Seventy-five albino male rats were randomly divided into five groups of 15 rats each. Rats in group 1 (control) were administered 10 mL/kg body weight distilled water (vehicle), group 2 received 60 mg/kg body weight sildenafil citrate (Viagra), while those in groups 3, 4, and 5 were given 300, 600, and 1,200 mg/kg body weight, respectively, of aqueous extract of Arctium lappa L. roots in the same volume. Female albino rats were made receptive by hormonal treatment. Sexual behavior parameters in male rats were monitored on days 3, 7 and 15 by pairing with receptive females (1:3). Male serum testosterone concentrations and potency were also determined. RESULTS: Oral administration of Arctium lappa L. roots extract at 600 and 1,200 mg/kg body weight significantly increased the frequencies of mount, intromission, and ejaculation frequency (p < 0.05). The latencies of mount and intromission were significantly reduced and ejaculation latency was prolonged. Administration of the extract also reduced the post-ejaculatory interval. The standard drug (Viagra) was more effective than the extract. The extract significantly increased the frequencies of all components of penile reflexes as well as serum testosterone levels, compared with the distilled water controls. CONCLUSIONS: The results of this study demonstrate that aqueous extract of Arctium lappa L. roots enhances sexual behavior in male rats. The aphrodisiac effects of the plant extract may be related to the presence of flavonoids, saponins, lignans and alkaloids, acting via a multitude of central and peripheral mechanisms. These results thus support the traditional use of Arctium lappa L. root extract for treating impotence and sterility. PMID- 22296877 TI - Estimating dose to implantable cardioverter-defibrillator outside the treatment fields using a skin QED diode, optically stimulated luminescent dosimeters, and LiF thermoluminescent dosimeters. AB - The purpose of this work was to determine the relative sensitivity of skin QED diodes, optically stimulated luminescent dosimeters (OSLDs) (microStarTM DOT, Landauer), and LiF thermoluminescent dosimeters (TLDs) as a function of distance from a photon beam field edge when applied to measure dose at out-of-field points. These detectors have been used to estimate radiation dose to patients' implantable cardioverter-defibrillators (ICDs) located outside the treatment field. The ICDs have a thin outer case made of 0.4- to 0.6-mm-thick titanium (~2.4-mm tissue equivalent). A 5-mm bolus, being the equivalent depth of the devices under the patient's skin, was placed over the ICDs. Response per unit absorbed dose-to-water was measured for each of the dosimeters with and without bolus on the beam central axis (CAX) and at a distance up to 20 cm from the CAX. Doses were measured with an ionization chamber at various depths for 6- and 15-MV x-rays on a Varian Clinac-iX linear accelerator. Relative sensitivity of the detectors was determined as the ratio of the sensitivity at each off-axis distance to that at the CAX. The detector sensitivity as a function of the distance from the field edge changed by +/- 3% (1-11%) for LiF TLD-700, decreased by 10% (5-21%) for OSLD, and increased by 16% (11-19%) for the skin QED diode (Sun Nuclear Corp.) at the equivalent depth of 5 mm for 6- or 15-MV photon energies. Our results showed that the use of bolus with proper thickness (i.e., ~d(max) of the photon energy) on the top of the ICD would reduce the scattered dose to a lower level. Dosimeters should be calibrated out-of-field and preferably with bolus equal in thickness to the depth of interest. This can be readily performed in clinic. PMID- 22296878 TI - Heart disease tradeoffs: the built environment, air pollution, and activity. PMID- 22296879 TI - A case with unilateral hypoglossal nerve injury in branchial cyst surgery. AB - An 11 years old boy came, with complain of mild dysarthria. Examination revealed marked hemiatrophy of left side of the tongue. Five months back he underwent ipsilateral branchial cyst operation. To our knowledge, no case was reported. After branchial cyst operation if there is any residual remnant chance of recurrence is very high. PMID- 22296880 TI - Microgravity simulation by diamagnetic levitation: effects of a strong gradient magnetic field on the transcriptional profile of Drosophila melanogaster. AB - BACKGROUND: Many biological systems respond to the presence or absence of gravity. Since experiments performed in space are expensive and can only be undertaken infrequently, Earth-based simulation techniques are used to investigate the biological response to weightlessness. A high gradient magnetic field can be used to levitate a biological organism so that its net weight is zero. RESULTS: We have used a superconducting magnet to assess the effect of diamagnetic levitation on the fruit fly D. melanogaster in levitation experiments that proceeded for up to 22 consecutive days. We have compared the results with those of similar experiments performed in another paradigm for microgravity simulation, the Random Positioning Machine (RPM). We observed a delay in the development of the fruit flies from embryo to adult. Microarray analysis indicated changes in overall gene expression of imagoes that developed from larvae under diamagnetic levitation, and also under simulated hypergravity conditions. Significant changes were observed in the expression of immune-, stress-, and temperature-response genes. For example, several heat shock proteins were affected. We also found that a strong magnetic field, of 16.5 Tesla, had a significant effect on the expression of these genes, independent of the effects associated with magnetically-induced levitation and hypergravity. CONCLUSIONS: Diamagnetic levitation can be used to simulate an altered effective gravity environment in which gene expression is tuned differentially in diverse Drosophila melanogaster populations including those of different age and gender. Exposure to the magnetic field per se induced similar, but weaker, changes in gene expression. PMID- 22296881 TI - Effects of copper and cadmium spiked-sediments on embryonic development of Japanese medaka (Oryzias latipes). AB - Because of their high capacity to accumulate contaminants such as persistent organic pollutants and heavy metals, aquatic sediments are considered as a long term source of contamination for aquatic organisms. In compliance with the increasing interest both for sediment quality evaluation and the use of fish early life stage (ELS) toxicity assays, we proposed an embryo-larval test to evaluate embryotoxicity and genotoxicity of sediment-bound contaminants. Pre blastula stage medaka (Oryzias latipes) embryos were exposed by static sediment contact to two model heavy metals (cadmium and copper) at environmental concentrations during the whole 10-day embryonic development. Lethal and sub lethal effects were recorded in both embryos and larvae for 20 days post fertilisation (dpf) using several global toxicity and phenotypic endpoints. The comet assay was also performed on medaka prolarvae to evaluate genotoxic effects of the tested chemicals. Environmental concentrations of cadmium (Cd) and copper (Cu) did not affect embryo and larval survival. However, both heavy metals significantly induced morphological abnormalities, particularly spinal and cardiovascular deformities. Cd but not Cu induced tachycardia. Both heavy metals induced a significant increase in DNA damage at all tested concentrations. Resulting LOEC values for Cd and Cu corresponded to 1.9 and 8.5 MUg/g d.w. sediment, respectively. Although metal bioavailability is probably lower for naturally contaminated sediments, the relatively low toxicity thresholds for both Cd and Cu raise the question of possible risk for fish embryos developing in direct contact to sediments. This study demonstrates the applicability, sensitivity and relevance of the Japanese medaka embryo-larval assay (MELA) to evaluate sediment hazardous potency at environmental concentrations of heavy metals. PMID- 22296882 TI - Human serum albumin stability and toxicity of anthraquinone dye alizarin complexone: an albumin-dye model. AB - The complexation between the primary vector of ligands in blood plasma, human serum albumin (HSA) and a toxic anthraquinone dye alizarin complexone, was unmasked by means of circular dichroism (CD), molecular modeling, steady state and time-resolved fluorescence, and UV/vis absorption measurements. The structural investigation of the complexed HSA through far-UV CD, three dimensional and synchronous fluorescence shown the polypeptide chain of HSA partially destabilizing with a reduction of alpha-helix upon conjugation. From molecular modeling and competitive ligand binding results, Sudlow's site I, which was the same as that of warfarin-azapropazone site, was appointed to retain high affinity for alizarin complexone. Moreover, steady state fluorescence displayed that static type and Forster energy transfer is the operational mechanism for the vanish in the tryptophan (Trp)-214 fluorescence, this corroborates time-resolved fluorescence that HSA-alizarin complexone adduct formation has an affinity of 10(5) M(-1), and the driving forces were found to be chiefly pi-pi, hydrophobic, and hydrogen bonds, associated with an exothermic free energy change. These data should be utilized to illustrate the mechanism by which the toxicological action of anthraquinone dyes is mitigated by transporter HSA. PMID- 22296883 TI - Direct cooling of the catheter tip increases safety for CMR-guided electrophysiological procedures. AB - BACKGROUND: One of the safety concerns when performing electrophysiological (EP) procedures under magnetic resonance (MR) guidance is the risk of passive tissue heating due to the EP catheter being exposed to the radiofrequency (RF) field of the RF transmitting body coil. Ablation procedures that use catheters with irrigated tips are well established therapeutic options for the treatment of cardiac arrhythmias and when used in a modified mode might offer an additional system for suppressing passive catheter heating. METHODS: A two-step approach was chosen. Firstly, tests on passive catheter heating were performed in a 1.5 T Avanto system (Siemens Healthcare Sector, Erlangen, Germany) using a ASTM Phantom in order to determine a possible maximum temperature rise. Secondly, a phantom was designed for simulation of the interface between blood and the vascular wall. The MR-RF induced temperature rise was simulated by catheter tip heating via a standard ablation generator. Power levels from 1 to 6 W were selected. Ablation duration was 120 s with no tip irrigation during the first 60 s and irrigation at rates from 2 ml/min to 35 ml/min for the remaining 60 s (Biotronik Qiona Pump, Berlin, Germany). The temperature was measured with fluoroscopic sensors (Luxtron, Santa Barbara, CA, USA) at a distance of 0 mm, 2 mm, 4 mm, and 6 mm from the catheter tip. RESULTS: A maximum temperature rise of 22.4 degrees C at the catheter tip was documented in the MR scanner. This temperature rise is equivalent to the heating effect of an ablator's power output of 6 W at a contact force of the weight of 90 g (0.883 N). The catheter tip irrigation was able to limit the temperature rise to less than 2 degrees C for the majority of examined power levels, and for all examined power levels the residual temperature rise was less than 8 degrees C. CONCLUSION: Up to a maximum of 22.4 degrees C, the temperature rise at the tissue surface can be entirely suppressed by using the catheter's own irrigation system. The irrigated tip system can be used to increase MR safety of EP catheters by suppressing the effects of unwanted passive catheter heating due to RF exposure from the MR scanner. PMID- 22296884 TI - The angiographic and clinical outcomes after coronary stenting in patients with metabolic syndrome. AB - BACKGROUND: Metabolic syndrome (MetS) is regarded as a risk factor for coronary artery disease (CAD). But the influence of MetS on morbidity and mortality after stent implantation in CAD patients remains unknown. METHODS: This article presents a meta-analysis of available data on the association between the MetS and the risk of angiographic and clinical outcomes following stent implantation. RESULTS: MetS was associated with a significant increased risk of post-stent all cause mortality (odd ratio (OR), 2.17, 95% CI, 1.56-3.01), in-lesion restenosis (OR, 1.35, 95% CI, 1.00-1.84) and major adverse cardiac events (MACE) (OR 1.35, 95% CI 1.13-1.61) in CAD patients. Even with drug-eluting stent (DES) implantation, significant increased risk in all-cause mortality (OR, 2.25, 95% CI, 1.61-3.15) and MACE (OR 1.42, 95% CI 1.14-1.76) were remain in patients with MetS. However, the OR of cardiovascular (CV) mortality (1.25, 95% CI 0.71-2.22), MI (1.27, 95% CI 0.87-1.85) and TLR (OR 1.21, 95% CI 0.96-1.53) was not statistically different between the patients with and without metabolic syndrome. CONCLUSIONS: Metabolic syndrome is an important risk factor in patients with CAD following stent implantation. Although DES implantation decreased the incidence of angiographic events, further progress in adequate treatment of MetS is still required to improve the clinical outcome. PMID- 22296885 TI - Effect of Omega-3 fatty acid supplementation on markers of platelet and endothelial function in patients with peripheral arterial disease. AB - OBJECTIVE: Omega-3 fatty acids have been shown to reduce platelet and endothelial activation in patients with or at risk of cardiac disease. We aimed to determine if Omega-3 fatty acid supplementation in addition to best medical therapy can reduce the increased platelet and endothelial activity that is present in patients with intermittent claudication. METHODS: One hundred and fifty patients who were receiving aspirin and statin therapy were recruited into a randomised cross-over double blind study involving 6 week supplementation with OMACOR fish oil (850-882 mg eicosapentaenoic and docosahexaenoic acid) versus placebo. A 12 week washout period occurred between treatments. Patients with diabetes were excluded. For each outcome a random effects model was fitted in which treatment and period were fixed effects and patients were random effects. RESULTS: Omega-3 supplementation had no effect on the primary outcome measure von Willebrand factor. Similarly Omega-3 supplementation resulted in no change in unstimulated or stimulated P-selectin expression and fibrinogen binding, or platelet aggregation (Ultegra point of care). Pulse wave velocity was also unchanged. High sensitivity C-reactive protein, s-ICAM and IL-6 were also unchanged. CONCLUSION: Supplementation with Omega-3 fatty acids had no affect on platelet and endothelial activation or markers of inflammation in patients with peripheral arterial disease. PMID- 22296886 TI - Relationship between ambulatory blood pressure and aortic arch atherosclerosis. AB - OBJECTIVE: Atherosclerotic plaque in the aortic arch is an independent risk factor for ischemic stroke. Although high blood pressure (BP) measured at the doctor's office is known to be associated with aortic atherosclerosis, little is known on the association between 24-h ambulatory BP and aortic arch plaque presence and severity. Our objective was to clarify the association between ambulatory BP variables and aortic arch atherosclerosis in a community-based cohort. METHODS: The study population consisted of 795 patients (mean age 71 +/- 9 years) participating in the Cardiovascular Abnormalities and Brain Lesions (CABL) study who underwent 24-h ambulatory BP monitoring (ABPM). Arch plaque was evaluated by 2D transthoracic echocardiography from a suprasternal window. RESULTS: All systolic ABPM variables (24-h/daytime/nighttime mean systolic BP, daytime/nighttime systolic BP variability) were associated with the presence of any plaque and large (>= 4 mm) plaque, whereas diastolic BP variables were not associated with aortic atherosclerosis. Multiple regression analysis indicated that nighttime systolic BP variability (expressed as the standard deviation of nighttime systolic BP) remained independently associated with large plaque after adjustment for age, sex, cigarette smoking, history of hypertension, diabetes mellitus, hypercholesterolemia, anti-hypertensive medication and nighttime mean systolic BP (odds ratio 1.39 per 1 standard deviation increase, 95% CI 1.00-1.93, P<0.05). CONCLUSION: Systolic ABPM variables are significantly associated with the presence of arch plaque. Nighttime systolic BP variability is independently associated with large arch plaque. These findings may have important implications in gaining further insights into the mechanism of arch plaque formation and progression. PMID- 22296887 TI - Comparison of in vitro and in vivo systems to study ica-independent Staphylococcus aureus biofilms. AB - The ability of Staphylococcus aureus to form biofilms is considered an important factor in the pathogenesis of central venous catheter-related bacteremia and infections associated with the use of medical prostheses. Different methods have been described for assessing staphylococcal biofilms, but few comparative studies have been attempted to evaluate these techniques; especially related to ica independent biofilm formation/accumulation. In this study we compared some in vitro and in vivo techniques to evaluate ica-independent biofilms produced by methicillin-resistant S. aureus. We observed that biofilms formed on human fibronectin-covered surfaces were about three times higher than those produced on inert polystyrene surfaces. However, despite the difference in absolute values, a linear correlation was detected between these two models. We also found that biofilms formed on polystyrene or polyurethane surfaces treated with human serum were easily detachable during washing and staining processes. The mouse model of subcutaneous foreign body showed good correlation with the in vitro techniques using either inert polystyrene or solid-phase fibronectin. Thus, our data showed that the microtiter-plate-based spectrophotometric assay is an appropriate method for preliminary biofilm investigations, mainly when a large number of isolates, mutants or systems need to be tested. PMID- 22296888 TI - [An infant with a painful swelling of the umbilicus]. AB - A 2-month-old boy with an congenital herniation of the umbilicus presented with a painful swelling of the umbilicus since 1 day, lower intake of food and vomiting. He had an incarcerated umbilical hernia. Eventually emergency surgery was needed. PMID- 22296889 TI - [Girl with ptosis, anisocoria and hemiparesis]. AB - A 9-year-old girl complained of a sudden severe headache during skiing, there was no previous trauma. She was nauseous, vomited and had weakness of the left arm and leg. She developed a right-sided ptosis, miosis and a contralateral hemiparesis, consistent with Horner's syndrome. MRI showed acute infarction of the right hemisphere caused by a dissection of the internal carotid artery. The patient recovered partially with rehabilitation. PMID- 22296890 TI - [A woman with a painful hip]. AB - A 85-year-old woman suffered persisting pain in her left hip after a fall. On X ray no fracture was seen. Her infection parameters were high and she developed a delirium and a painful swelling on her left hip. Examination with ultrasound showed free gas in the soft tissue of the left hip. A CT-scan of the abdomen and left upper leg showed a ruptured abscess in the left kidney with free gas, spreading through the M. iliopsoas into the upper left leg. On request of the patient and her family no treatment was given. PMID- 22296891 TI - [A man stuck to a drain]. AB - A 54-year-old man underwent a robot assisted laparoscopic prostatectomy (RALP) because of prostate cancer. During surgery an open silicone drain was placed in the abdominal cavity. After a few days we tried to remove the drain, however it was stuck to a bloodclot and to a tissue structure protruding from the abdominal cavity. This proved to be the appendix vermiformis. The drain was safely removed and the appendix was pushed back into the abdominal cavity successfully. The patient suffered no consequences of this complication. PMID- 22296892 TI - [Acute pulmonary embolism: beware of the wolf in sheep's clothing]. AB - Two male patients aged 57 and 73 were referred to the cardiologist because of progressive dyspnoea. In one patient, the general practitioner had previously adopted an expectative policy because of a clean chest X-ray. At presentation after 4 weeks, the patient was diagnosed with and treated for acute coronary syndrome because of minor ECG abnormalities. Additional CT scanning showed a large saddle embolus. Despite adequate treatment, the patient suffered an electrical asystole and died. The other patient underwent ECG, bicycle ergometry, MRI adenosine, echocardiography and lung function tests over a period of 5 weeks before pulmonary embolism (PE) was diagnosed. As the signs and symptoms of PE are largely non-specific, diagnostic delay is common, with risk of poor clinical outcome. PE should at least be considered whenever a patient presents with acute or worsening breathlessness, chest pain, circulatory collapse or coughing, particularly in the presence of known thrombotic risk factors or when there is no clear alternative. PMID- 22296893 TI - [Revised practice guideline 'Anaemia in midwifery practice']. AB - The practice guideline of the Royal Dutch Organization of Midwives 'Anaemia in primary care midwifery practice' published in 2000, has recently been revised. The revised guideline takes physiological haemodilution during pregnancy into consideration and provides gestation specific reference values for haemoglobin levels. The guideline advises to start iron supplementation only in demonstrated iron deficiency based on low levels of haemoglobin and mean corpuscular volume (MCV). This results in less prescription of iron medications and prescription of lower dosages, which will result in fewer adverse effects and better therapy adherence. New chapters are added concerning anaemia during preconception and the puerperium. More attention is given to women with an increased risk of anaemia in pregnancy and the influence of a positive carrier status for haemoglobinopathy. In order to achieve good continuity of care, collaboration between obstetricians and general practitioners is important. PMID- 22296894 TI - [Shoulder pain due to suprascapular neuropathy]. AB - BACKGROUND: Shoulder complaints are caused by suprascapular neuropathy in 1-2% of patients. This rare condition is characterised by slowly progressing shoulder pain, which has as a consequence restriction of movement and loss of strength. The most frequent causes are tear of the rotator cuff or a space occupying lesion. CASE DESCRIPTION: A 30-year-old man presented with slowly arising shoulder pain with subsequent also loss of strength and atrophy of the shoulder. A MRI scan of the shoulder showed a cyst in the glenoid cavity. Using EMG suprascapular neuropathy was diagnosed. The cyst was removed by operation and the patient recovered well. CONCLUSION: The diagnosis 'suprascapular neuropathy' was made using EMG. Space occupying lesions of the shoulder can be excluded by X-ray and MRI. The treatment is primarily conservative, with physiotherapy and pain management. PMID- 22296895 TI - [Cost-effectiveness: euros per QALY is not enough]. AB - The number of economic evaluations being published in scientific literature each year is increasing exponentially. Cost-effectiveness seems to be playing an increasing role in decisions about reimbursement or the implementation of curative or preventive interventions. A cost-effectiveness ratio represents the fraction between the costs and effects that are associated with an intervention. What costs are included in the numerator of the fraction? What assumptions on effectiveness and reach are made to express the denominator? Various examples have shown that small differences in assumptions can have significant consequences for the cost-effectiveness ratio. This holds true for presumptions on the long-term effects of an intervention as well as the willingness to participate in an intervention. Such assumptions and choices can sometimes highly determine the outcome of a cost-effectiveness analysis. For this reason, caution in interpreting results of cost-effectiveness analyses is warranted. PMID- 22296896 TI - [Fever, malaise and eosinophilia after consumption of raw fish in Italy: infection by a liver fluke (Opisthorchis felineus)]. AB - BACKGROUND: Infection by a liver fluke (trematode) is rare in Western Europe, but recently a few outbreaks caused by this parasite have been described after consumption of raw freshwater fish caught in Italy. CASE DESCRIPTION: A 35-year old Dutch woman presented with fever, without localising symptoms. Laboratory tests showed pronounced eosinophilia. Microscopy of the faeces showed a liver fluke egg. Upon inquiry, it appeared that she had consumed raw fish (carpaccio of tench) three weeks earlier in a restaurant in Northern Italy. In Italy, 45 people with comparable symptoms were found to be infected by the same parasite. All patients had eaten in the same restaurant. They were treated successfully with praziquantel. The stool egg was from the trematode Opisthorchis felineus. CONCLUSION: O. felineus lives in the bile ducts of fish-eating mammals. Its life cycle includes freshwater snails and fish. Acute symptoms are fever, malaise and abdominal pain and complications such as liver and bile duct abscesses and cholangitis. Diagnosis is made by microscopic examination of the faeces, confirmed by PCR or by serology. PMID- 22296897 TI - [Simulation in the general hospital: differential diagnosis and policy]. AB - Doctors meet patients who present with non-genuine diseases. We present three patients who present with an illness with no organic cause: conversion syndrome, factitious disorder and simulation. We discuss the differential diagnosis, prevalence and diagnostics in the event of simulation. A proposal is made about how to respond in the event of simulation. The method is similar to the treatment of a factitious disorder: limitation of the potential benefits attached to the sick role; confrontation with medical facts; maintaining the doctor-patient relationship. PMID- 22296898 TI - [On the way to eradicating malaria]. AB - The new global strategy to achieve long-term malaria eradication is based on rapid treatment of individual malaria patients and blocking the spread of Plasmodium parasites in the population. In a number of countries increased funding combined with more effective control measures have resulted in a substantial decline in the incidence of malaria and in the resulting morbidity and mortality. Increasing resistance of Anopheles mosquitoes to insecticides (pyrethroids and DDT), and reduced sensitivity of Plasmodium parasites to various antimalarials increase the need for the development of new vector control strategies and medicines. Vaccine development efforts have been speeding up and a first vaccine is expected within three years. PMID- 22296899 TI - [Van den Spiegel and his line]. AB - Adriaan van den Spiegel or Spigelius (1578-1625) was born in Flanders to protestant parents. His father was court surgeon to William, Prince of Orange. Adriaan studied medicine in Leiden and obtained a doctoral degree in Padua. In 1616, after a period as physician to the German-Dutch student community in Padua and as court physician in central Europe, he was appointed professor of anatomy and surgery, succeeding Fabritius (1533-1619) and Casserius (1552-1616). He planned to publish a modern atlas of anatomy with etchings from the legacy of Casserius, to replace Vesalius' De humani corporis fabrica libri septem of 1543. Unfortunately he was cut short by death, like his predecessor. Eventually his pupil Bucretius published the atlas in 1627, with 78 of Casserius' illustrations and 20 new ones. In the text Spigelius calls attention to the aponeurotic fascia of the transverse and oblique abdominal muscles, on either side of the rectus abdominis muscle. He proposes the name linea semilunaris, now the official term. PMID- 22296900 TI - [Summary of the Dutch College of General Practitioners (NHG) practice guideline on 'Diverticulitis']. AB - The NHG practice guideline on 'Diverticulitis' provides general practitioners with directions on the diagnosis and treatment of uncomplicated and complicated diverticulitis. Diverticulitis is primarily a clinical diagnosis which can be supported by assessment of CRP. Uncomplicated diverticulitis is strongly suspected if the patient reports the development of persistent sharp, stabbing pain in the lower left abdomen within a couple of days; if there is pressure or rebound tenderness only in the lower left abdomen; and if there are no alarm signals. Alarm signals of complicated diverticulitis are: guarded muscle response, signs of intestinal obstruction, locally palpable resistance, rectal loss of blood, hypotension, and high fever. The policy for uncomplicated diverticulitis is waiting without specific measures, provided that the general practitioner monitors the course actively. There is no indication for antibiotics in patients with uncomplicated diverticulitis. Patients with signs of complicated diverticulitis or with persisting symptoms should be referred. PMID- 22296901 TI - [Wide support for oocyte donation and banking in the Netherlands]. AB - OBJECTIVE: To assess the general consensus on the cryopreservation of oocytes and the introduction of oocyte banking facilities in the Netherlands. DESIGN: Poll investigation METHOD: A poll with the use of an online questionnaire was conducted among nearly 19,000 participants of the Dutch EenVandaag opinion panel in May 2011. The poll results were adjusted to the Dutch population based on data from the Dutch Central Office for Statistics for age, gender, education, marital status, geographical area and political preference (measured according to the lower house elections of 2010). The primary endpoints were the percentages of supporters of oocyte freezing for own future use and of the concept of introducing oocyte banking facilities in The Netherlands. The secondary endpoints were the demographic differences between supporters and opponents. RESULTS: Approximately half of 18.911 participants supported oocyte freezing (47%). Fifty percent of all participants supported oocyte banking in the Netherlands. Supporters of oocyte freezing were mainly women <= 45 years of age, who are highly educated and have no children. Four percent of the participating women aged <= 45 years would seriously consider obtaining donor oocytes from an available oocyte banking facility. Twelve percent of the participating women <= 45 years of age said they would definitely donate their oocytes or would seriously consider donating. Thirty-seven percent of all participants were against the introduction of oocyte banking facilities. The most important arguments against oocyte freezing were that women should reproduce during normal reproductive years and that it was not medically necessary. CONCLUSION: Poll results showed much support for oocyte freezing and for the introduction of oocyte banking facilities in the Netherlands. In addition, the poll shows that oocyte banking facilities would fulfil a need in the population. PMID- 22296902 TI - [Revised practice guideline 'Management of patients with mild traumatic head/brain injury']. AB - Recently the out-of-date Dutch guideline 'Mild traumatic head/brain injury' dating from 2001 was revised under the supervision of the Dutch Institute for Healthcare Improvement (CBO). The revised guideline gives underpinned decision rules for the referral of patients to hospital, carrying out diagnostic imaging investigations, and formulating indications for admission. Mild head-brain injury is no longer an indication for a conventional skull radiograph. Adults and children aged 6 years and older no longer have to be woken regularly if they are allowed home. The guideline can be used in both primary care and on the Emergency Departments of hospitals and is applicable to both adults and children. The guideline does not address the rehabilitation or long-term care of patients with mild traumatic head/brain injury, but it does give advice on reducing the risk of long-term symptoms. Regional implementation of the guideline in primary and secondary care is recommended. PMID- 22296903 TI - [Operated on for epilepsy: cured or not?]. AB - The idea behind epilepsy surgery is that a patient is cured from epilepsy by brain surgery. Is this true? A recent paper in The Lancet shows that this view is too simple. Seizures can recur years after surgery, and of all patients who became seizure free only a minority no longer has to take anti-epileptic drugs. This does not alter the fact that epilepsy surgery holds the best perspectives for many patients. PMID- 22296904 TI - [The Dutch guideline 'Renal cell carcinoma']. AB - The Dutch guideline 'Renal Cell Carcinoma' has been revised on the basis of new literature. With the assistance of the Netherlands Cancer Registry an assessment was made of the current care for patients with renal cell carcinoma. Renal cell carcinoma is a type of cancer for which knowledge of the genetic basis of the different histological subtypes has led to the development of new targeted therapies. By the introduction of these systemic therapies, histological subtyping of renal cell carcinoma has become more important. Although in the previous guideline cytological or histological diagnosis was recommended to determine the nature of the tumourous process in the kidney, in the revision it is advised to use histological needle biopsies to determine the histological subtype and therefore to provide evidence for the choice of systemic therapy. With modern diagnostic techniques, more patients with smaller tumours are identified. For these tumours, less invasive therapies are recommended in order to preserve as much renal tissue as possible. PMID- 22296905 TI - [Better pain management in chronic pancreatitis through early surgery?]. AB - The most important symptom in patients with chronic pancreatitis is pain. This is often difficult to treat. The current treatment consists of, successively, optimal medical treatment, endoscopic intervention and finally surgical intervention. Previous research has indicated that early surgical intervention leads to better pain management and preservation of pancreatic function. Recently, the randomised multicentre 'Early surgery versus optimal current step up practice for chronic-pancreatitis' (ESCAPE) trial was started in order to evaluate whether early surgery provides better reduction of pain in comparison with present treatment. In addition, serious complications, mortality, cost effectiveness, quality of life, pancreas insufficiency, alternative pain scores, hospital admissions and the number of interventions will be assessed. PMID- 22296906 TI - [Implementation of hemovigilance in Sub-Saharan Africa]. AB - PURPOSE OF THE STUDY: Hemovigilance being an essential part of blood transfusion safety, many countries have set legislation for its organization and its establishment. In Sub-Saharan Africa, where transfusion practice is facing many challenges, hemovigilance does not always appear as a priority. Nevertheless, in 2000, Burkina Faso decided to reorganize its blood transfusion system according to the World Health Organisation recommendations and other international standards. A national blood transfusion center and regional blood transfusion centers were created. From 2005 to 2009, a hemovigilance pilot project was conducted by the regional blood transfusion center of Bobo-Dioulasso. METHODS: The implementation of this hemovigilance project included the following steps: training of medical and paramedical personnel of the health facilities provided with blood and blood products by the regional blood transfusion center, distribution of post transfusion and hemovigilance forms, and the creation of a hemovigilance and transfusion committee. RESULTS: During the period 2005-2009, 34,729 blood products were distributed for 23,478 patients. The return rate of the post-transfusion and hemovigilance forms (number of files completed partially or completely and returned to the regional blood transfusion center compared to the number of units distributed) raised from 83.1 to 94.8%, the rate of traceability (rate of forms returned to the regional blood transfusion center and totally completed) raised from 71.6 to 91.6%, and the concordance between the patient for which the blood was delivered and the patient transfused moved from 92.9 to 98.0%. The notification rate of transfusion incidents raised from 1.1 to 16.1 per 1000 units transfused during that period. CONCLUSION: The implementation of a hemovigilance system is possible in the Sub-Sahara African countries. This constitutes a major element in the improvement of different steps of transfusion safety. The implementation of a hemovigilance system requires negotiations between transfusion centers and the hospital personnel, and should be facilitated by the official regulation on blood transfusion practices. PMID- 22296907 TI - Getting the timing right. PMID- 22296908 TI - Association study of clusterin polymorphism rs11136000 with late onset Alzheimer's disease in Chinese Han population. AB - OBJECTIVE: We conducted a case-control study to investigate whether clusterin polymorphism (rs11136000) was associated with late-onset Alzheimer's disease in Chinese Han population. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was performed on genotype rs11136000 and APOEepsilon4 in 127 patients with late-onset Alzheimer's disease and 143 control individuals. Previous published data from other Chinese samples was also included for further meta-analysis. RESULTS: APOEepsilon4 was demonstrated to increase the risk of Alzheimer's disease in Chinese population (odds ratio = 2.35, 95% confidence interval: 1.40-3.96). There is no significant association between clusterin rs11136000 with late-onset sporadic AD in our small cohort. However, meta-analysis revealed significant allele and genotype differences between Alzheimer's disease and controls following a recessive model. CONCLUSION: Clusterin (rs11136000) was associated with Alzheimer's disease in Chinese Han population. PMID- 22296909 TI - The informal caregivers' perception of wandering. AB - Although the term wandering is routinely used by clinicians, researchers, and informal caregivers (ICs), the meaning of this term varies depending on the source of the definition and the context in which it is used. The purpose of this study was to examine the terms ICs used to describe different scenarios that have been identified in literature as "wandering," determine their perception of risk, and compare their definitions of wandering with the perspectives of researchers. Structured interviews were conducted with 128 ICs of older adults with dementia. Informal Caregivers rarely used the term wandering to label different scenarios that had been previously identified in the literature as wandering. Responses to a survey of 17 wandering experts did not reflect agreement on a definition for wandering. These findings suggest that a broad set of terms should be used to describe this potentially dangerous behavior when health care providers communicate with ICs. PMID- 22296910 TI - Palliative care for advanced dementia: a pilot project in 2 nursing homes. AB - This article describes a pilot project involving training, case consultations, and administrative coaching over a period of 1 year aimed at introducing palliative care in 2 nursing homes among 31 residents with advanced dementia. Resident outcomes that examined numerous clinical measures were assessed at 3 points in time. Changes in the knowledge and attitudes of 80 staff members and 33 family members who participated in the multimodal intervention were also assessed at 3 points in time. Limited improvements were demonstrated on measures for residents, staff members, and family members at the first nursing home (site 1) and significant improvements were demonstrated at the other nursing home (site 2). Top leadership turned over 3 times at site 1 which limited the integration of palliative care, whereas leadership of site 2 remained stable. Implications for implementing a program of palliative care in nursing homes are discussed. PMID- 22296911 TI - Revealing interaction mode between HIV-1 protease and mannitol analog inhibitor. AB - HIV protease is a key enzyme to play a key role in the HIV-1 replication cycle and control the maturation from HIV viruses to an infectious virion. HIV-1 protease has become an important target for anti-HIV-1 drug development. Here, we used molecular dynamics simulation to study the binding mode between mannitol derivatives and HIV-1 protease. The results suggest that the most active compound (M35) has more stable hydrogen bonds and stable native contacts than the less active one (M17). These mannitol derivatives might have similar interaction mode with HIV-1 protease. Then, 3D-QSAR was used to construct quantitative structure activity models. The cross-validated q(2) values are found as 0.728 and 0.611 for CoMFA and CoMSIA, respectively. And the non-cross-validated r(2) values are 0.973 and 0.950. Nine test set compounds validate the model. The results show that this model possesses better prediction ability than the previous work. This model can be used to design new chemical entities and make quantitative prediction of the bioactivities for HIV-1 protease inhibitors before resorting to in vitro and in vivo experiment. PMID- 22296912 TI - [Solution to case 39. Calcifying epithelial odontogenic tumor (pindborg tumor)]. PMID- 22296913 TI - Carpal arthritis as the initial manifestation of Gitelman's syndrome. PMID- 22296914 TI - Autonomic dysreflexia in a tetraplegic patient due to a blocked urethral catheter: spinal cord injury patients with lesions above T-6 require prompt treatment of an obstructed urinary catheter to prevent life-threatening complications of autonomic dysreflexia. AB - BACKGROUND: The Manchester Triage System is commonly used as the triage system in emergency departments of the UK. As per the Manchester Triage System, patients presenting with retention of urine to the accident and emergency department are categorized to yellow, which denotes that the ideal maximum time to first contact with a treating clinician will be 60 min. Cervical spinal cord injury patients, in whom urinary catheter is blocked, may develop suddenly headache, sweating, high blood pressure, cardiac dysrhythmia, convulsions, intracranial bleed, and acute neurogenic pulmonary oedema as a result of autonomic dysreflexia due to a distended bladder. CASE PRESENTATION: A 46-year-old male with C-6 tetraplegia developed urinary retention because of a blocked catheter. He was seen immediately on arrival in the spinal injuries unit. The blocked catheter was removed and a new catheter was about to be inserted. Then this patient said that the ceiling lights were very bright and glaring. Five milligrams of Nifedipine was given sublingually. This patient started having fits involving his head, face, neck and shoulders with loss of consciousness. A 14-French silicone Foley catheter was inserted per urethra without any delay and 300 ml of clear urine was drained. This patient recovered consciousness within 5 min. Computed tomography of the brain revealed no focal cerebral or cerebellar abnormality. There was no intra-cranial haemorrhage. CONCLUSION: This case illustrates that spinal cord injury patients with lesion above T-6, who develop retention of urine because of a blocked catheter, may look apparently well, but these patients can develop suddenly life-threatening autonomic dysreflexia. Therefore, spinal cord injury patients, who present to the accident and emergency department or spinal units with a blocked urinary catheter, should be seen urgently although their vital signs may be stable on arrival. Increasing the awareness of staff in emergency departments regarding autonomic dysreflexia as well as education of the patient and carers will be useful in preventing this complication in persons with spinal cord injury. PMID- 22296915 TI - Sensations in restless legs syndrome. AB - OBJECTIVE: To characterize the verbal descriptors of the sensations in restless legs syndrome (RLS) in depth. METHODS: Fifty-six patients with primary RLS (interviewed in person) and 738 members of the French RLS Association (sent a postal questionnaire) were included in the study. Patients in the clinical series were asked to report their RLS sensations in detail. The two groups completed a French reconstruction of the McGill Pain Questionnaire (QDSA) to assess their RLS sensations. RESULTS: All patients in both groups had abnormal sensations associated with the urge to move the legs. Most patients in the clinical series reported spontaneous "electrical," "prickling," "burning," "tingling," and "itching" sensations. In the QDSA, more than two-thirds of subjects in both groups selected the sensory subclasses "temporal" and "paresthesias," and the affective subclasses "evaluative," "nervous tension," "asthenia, fatigue," and "punishment." More than one-third of subjects chose the sensory words "electric shocks," "irradiating," and "tingling," and the affective words "exhausting," "distressing," "unbearable," "irritating," and "depressing." The subjects used more heat than cold descriptors to express their sensations. CONCLUSION: RLS is a primary sensory disorder without any pure motor form. The sensory descriptors in RLS could be similar to those of neuropathic pain, except for rare cold and numbness sensations. PMID- 22296916 TI - Nutritional knowledge in hemodialysis patients and nurses: focus on phosphorus. AB - OBJECTIVE: To assess the knowledge of adult hemodialysis patients and nurses working in dialysis units, specifically with regard to knowledge of phosphorus and other nutrients related to dietary management of end-stage renal disease. DESIGN: Cross-sectional cohort study. SETTING: Hemodialysis unit. SUBJECTS: One hundred ninety-one hemodialysis patients and 105 dialysis nurses, as well as 86 control hospital employees who are not health professionals. INTERVENTION: Nutritional knowledge was assessed by a 25-item chronic kidney disease knowledge assessment tool for nutrition, which includes 15 questions on phosphorus and 10 questions on protein, sodium, and potassium knowledge. RESULTS: The scores obtained by patients were much lower than those of nurses (11.6 +/- 3.9 vs. 16.0 +/- 2.2, P < .001) but slightly higher than those of controls (10.6 +/- 3.2, P < .05). Patients with phosphorus serum level >5.5 mg/dL showed chronic kidney disease knowledge assessment tool for nutrition scores similar to those of patients with a serum phosphorus level <5.5 mg/dL. The prevalence of right answers to questions regarding knowledge of phosphorus was lower than that regarding knowledge of the other nutrients, both for patients (38.4% +/- 17.8% vs. 57.3% +/- 19.9%, P < .001) and nurses (55.6% +/- 11.1% vs. 74.8% +/- 11.7%, P < .001) as well as for controls (30.7% +/- 14.5% vs. 60.1% +/- 17.4%, P < .001). CONCLUSIONS: Our study suggests that nutritional knowledge of hemodialysis patients, although higher than the general population, is lower for phosphorus with respect to the other nutrients, such as protein, sodium, and potassium. This occurs even in patients with hyperphosphatemia or those taking phosphate binder medications. Nurses showed the best scores; however, improvement is necessary, especially with regard to knowledge of phosphorus. Training programs on nutrition for nurses and on information for patients should be implemented. They can contribute to achievement of a more effective control of phosphate balance, reduction of costs, and improvement of the quality of care for hemodialysis patients. PMID- 22296917 TI - Pica: an important and unrecognized problem in pediatric dialysis patients. AB - OBJECTIVE: Pica is the compulsive consumption of non-nutritive substances, and this disorder may occur more frequently in dialysis patients. The purpose of our study was to determine the prevalence of pica and the associated demographic and metabolic characteristics. DESIGN: Retrospective, cross-sectional analysis. SETTING: Hospital-based, outpatient, pediatric hemodialysis unit. SUBJECTS: Eighty-seven pediatric patients on chronic dialysis therapy were interviewed. Sixty-seven patients were receiving hemodialysis, whereas the remaining 20 were maintained on peritoneal dialysis. The predominantly nonwhite (93%) patient population had a mean age of 17.2 +/- 7.2 years. Dialysis efficiency, estimated by urea clearance per patient volume (Kt/V), averaged 1.5 +/- 0.5. INTERVENTION: Standard patient interview and documentation of laboratory and dialytic parameters. MAIN OUTCOME MEASURE: Prevalence of pica and associated comorbid conditions. RESULTS: The survey indicated that 46% of patients experienced pica, further divided into simple "ice" pica (34.5%) versus "hard" pica (12.6%). Hard pica included the consumption of chalk, starch, sugar, soap, sand, clay, Ajax cleanser, sponge, wood, and potting soil. Patients on hemodialysis were 8.3 times more likely to have hard pica compared with those on peritoneal dialysis. Greater than 5 years on dialysis was associated with a 3.2 odds ratio of having pica (P = .02). Anemia was the most significant morbid association, occurring at an odds ratio of 4.4 (P = .001) for all pica and 10.6 (P = .004) for hard pica. CONCLUSION: Pica, therefore, is prevalent and potentially harmful, requiring further attention in the nutritional management of pediatric dialysis patients. PMID- 22296918 TI - Digestive utilization of ozone-exposed forage by rabbits (Oryctolagus cuniculus). AB - A mixture of common Southern Piedmont (USA) grassland species (Lolium arundinacea, Paspalum dilatatum, Cynodon dactylon and Trifolium repens) was exposed to O(3) [ambient (non-filtered; NF) and twice-ambient (2X) concentrations] and fed to individually caged New Zealand white rabbits (Oryctolagus cuniculus) in a digestibility experiment. Forages and feed refusals were analyzed for concentrations of total cell wall constituents, lignin, crude protein, and soluble and hydrolyzable phenolic fractions. Neutral detergent fiber and acid detergent fiber digestibility by rabbits were significantly lower for 2X than NF forage. Decreased digestibility could not be attributed to lignin concentrations, but was associated with increased concentrations of acid hydrolyzable and saponifiable phenolics. Exposure of forage to elevated O(3) resulted in decreased digestible dry matter intake by rabbits. Elevated O(3) concentrations could be expected to have a negative impact on forage quality, resulting in decreased nutrient utilization by mammalian herbivores in Southern Piedmont grasslands under projected future climate scenarios. PMID- 22296919 TI - How does lean work in emergency care? A case study of a lean-inspired intervention at the Astrid Lindgren Children's hospital, Stockholm, Sweden. AB - BACKGROUND: There is growing interest in applying lean thinking in healthcare, yet, there is still limited knowledge of how and why lean interventions succeed (or fail). To address this gap, this in-depth case study examines a lean-inspired intervention in a Swedish pediatric Accident and Emergency department. METHODS: We used a mixed methods explanatory single case study design. Hospital performance data were analyzed using analysis of variance (ANOVA) and statistical process control techniques to assess changes in performance one year before and two years after the intervention. We collected qualitative data through non participant observations, semi-structured interviews, and internal documents to describe the process and content of the lean intervention. We then analyzed empirical findings using four theoretical lean principles (Spear and Bowen 1999) to understand how and why the intervention worked in its local context as well as to identify its strengths and weaknesses. RESULTS: Improvements in waiting and lead times (19-24%) were achieved and sustained in the two years following lean inspired changes to employee roles, staffing and scheduling, communication and coordination, expertise, workspace layout, and problem solving. These changes resulted in improvement because they: (a) standardized work and reduced ambiguity, (b) connected people who were dependent on one another, (c) enhanced seamless, uninterrupted flow through the process, and (d) empowered staff to investigate problems and to develop countermeasures using a "scientific method". Contextual factors that may explain why not even greater improvement was achieved included: a mismatch between job tasks, licensing constraints, and competence; a perception of being monitored, and discomfort with inter-professional collaboration. CONCLUSIONS: Drawing on Spear and Bowen's theoretical propositions, this study explains how a package of lean-like changes translated into better care process management. It adds new knowledge regarding how lean principles can be beneficially applied in healthcare and identifies changes to professional roles as a potential challenge when introducing lean thinking there. This knowledge may enable health care organizations and managers in other settings to configure their own lean program and to better understand the reasons behind lean's success (or failure). PMID- 22296920 TI - Differential effects of intermittent and continuous exposure to novel environmental stimuli on the development of amphetamine-induced behavioral sensitization in mice: implications for addiction. AB - BACKGROUND: Previous studies have demonstrated a preventive effect of continuous environmental enrichment during early development on the vulnerability of rodents to drug addiction-related behaviors. Recently, it was demonstrated that a continuous environmental enrichment could eliminate already established addiction related behaviors in mice. The present study compared the effects of intermittent or continuous exposure to novel stimuli during repeated amphetamine (Amp) treatment on the development of behavioral sensitization (an animal model of addiction-related neuroadaptations) in adult mice. METHODS: Three-month-old male Swiss mice were treated with 2.5mg/kg Amp every other day for 13 days in their home cages. Novel objects were presented in their home cages for 2h on non-drug treatment days (experiment 1) or for 24h/day during the 13 days of drug treatment (experiment 2). Seven days after the drug treatment had finished, the mice were challenged with 2.5mg/kg Amp, and their locomotor activity was quantified in a familiar open field for 10 min. RESULTS: Intermittent exposure to the novel objects did not modify the acute Amp locomotor stimulatory effect but potentiated the development of Amp-induced locomotor sensitization. This enhanced sensitization was due to increased locomotion in the central squares of the apparatus, which suggests anxiolysis or increased impulsiveness. Conversely, continuous exposure to the novel objects potentiated the acute Amp locomotor stimulatory effect and blunted the development of Amp-induced locomotor sensitization. CONCLUSIONS: We conclude that addiction-related behaviors can be differentially and critically modified depending on the schedule and period of the novelty exposure. PMID- 22296921 TI - Towards a molecular view of transcriptional control. AB - The accumulation of experimental data over recent years has fueled theoretical work on how transcription factors (TFs) search for and recognise their DNA target sites, how they interact with one another, or with other DNA-binding proteins, and how they cope with the compaction of DNA within bacterial nucleoids or within eukaryotic chromatin. Many models have been built to study the kinetic, thermodynamic and mechanistic aspects of these questions. In some cases they have resulted in a relatively clear consensus view, but a number of questions remain controversial. We present an overview of recent work, with an emphasis on models that provide, or can inspire, a better understanding of transcriptional control at a detailed molecular level. PMID- 22296922 TI - Infectious mononucleosis-like syndrome probably attributable to Coxsackie A virus infection. AB - Infectious mononucleosis (IM) is a clinical syndrome most often attributable to Epstein-Barr virus (EBV). Characteristic clinical features of EBV IM include bilateral upper lid edema, exudative or nonexudative pharyngitis, bilateral posterior cervical adenopathy, and splenomegaly +/- maculopapular rash. Laboratory features of EBV IM include atypical lymphocytes and elevated levels of serum transaminases. Leukopenia and thrombocytopenia are not uncommon. The syndrome of IM may also be attributable to other infectious diseases, eg, cytomegalovirus (CMV), human herpes virus-6 (HHV-6), or Toxoplasma gondii. Less commonly, viral hepatitis, leptospirosis, brucellosis, or parvovirus B(19) may present as an IM-like infection. To the best of our knowledge, only 2 cases of IM like infections attributable to Coxsackie B viruses (B(3) and B(4)) have been reported. We present the first reported case of an IM-like syndrome with sore throat, fatigue, atypical lymphocytes, and elevated levels of serum transaminases likely due to Coxsackie A in an immunocompetent adult. PMID- 22296924 TI - [Colonic diverticular disease: diagnosis and therapy]. AB - Colonic diverticular disease is one of the most common gastrointestinal disorders in the Western world, affecting approximately 50% of the population above the age of 70 years. Symptoms develop only in about one quarter of the affected individuals with complications in one-third of the symptomatic patients. Diagnosis is mostly confirmed by colonoscopy. Abdominal CT is the most sensitive for the diagnosis of complicated severe diverticulitis, while colonoscopy or in severe cases angiography may be performed in bleeding patients. Initial therapy of non-complicated symptomatic diverticulitis includes antibiotics and more recently non-absorbable antibiotics. In complicated cases should be treated with broad spectrum i.v. antibiotics, however surgery may became necessary in a minority of the cases. The proportion of patients needing acute surgical intervention has decreased in the last decades with the advancement of conservative management including medical therapy, endoscopy and imaging techniques and the indication of elective was also changed. PMID- 22296923 TI - Gene alterations at Drosophila inversion breakpoints provide prima facie evidence for natural selection as an explanation for rapid chromosomal evolution. AB - BACKGROUND: Chromosomal inversions have been pervasive during the evolution of the genus Drosophila, but there is significant variation between lineages in the rate of rearrangement fixation. D. mojavensis, an ecological specialist adapted to a cactophilic niche under extreme desert conditions, is a chromosomally derived species with ten fixed inversions, five of them not present in any other species. RESULTS: In order to explore the causes of the rapid chromosomal evolution in D. mojavensis, we identified and characterized all breakpoints of seven inversions fixed in chromosome 2, the most dynamic one. One of the inversions presents unequivocal evidence for its generation by ectopic recombination between transposon copies and another two harbor inverted duplications of non-repetitive DNA at the two breakpoints and were likely generated by staggered single-strand breaks and repair by non-homologous end joining. Four out of 14 breakpoints lay in the intergenic region between preexisting duplicated genes, suggesting an adaptive advantage of separating previously tightly linked duplicates. Four out of 14 breakpoints are associated with transposed genes, suggesting these breakpoints are fragile regions. Finally two inversions contain novel genes at their breakpoints and another three show alterations of genes at breakpoints with potential adaptive significance. CONCLUSIONS: D. mojavensis chromosomal inversions were generated by multiple mechanisms, an observation that does not provide support for increased mutation rate as explanation for rapid chromosomal evolution. On the other hand, we have found a number of gene alterations at the breakpoints with putative adaptive consequences that directly point to natural selection as the cause of D. mojavensis rapid chromosomal evolution. PMID- 22296925 TI - [Beyond genetics--the emerging role of epigenetics and its clinical aspects]. AB - Analysis of genomic sequences has clearly shown that the genomic differences among species do not explain the diversity of life. The genetic code itself serves as only a part of the dynamic complexity that results in the temporal and spatial changes in cell phenotypes during development. It has been concluded that the phenotype of a cell and of the organism as a whole is more influenced by environmentally-induced changes in gene activity than had been previously thought. The emerging field of epigenetics focuses on molecular marks on chromatin; called the epigenome, which serve as transmitters between the genome and the environment. These changes not only persist through multiple cell division cycles, but may also endure for multiple generations. Irregular alterations of the epigenome; called epimutations, may have a decisive role in the etiology of human pathologies such as malignancies and other complex human diseases. Epigenetics can provide the missing link between genetics, disease and the environment. Therefore, this field may have an increasing impact on future drug design and serve as a basis for new therapeutic/preventative approaches. PMID- 22296926 TI - [Autoimmune comorbidity and microvascular complications in childhood-onset type 1 diabetes after 20 years of diabetes duration: a questionnaire study]. AB - There are no population-based data on the autoimmune morbidity and vascular complications of young adults with childhood-onset type 1 diabetes in Hungary. AIMS: To assess the prevalence of these morbidities after 20 years of diabetes duration. METHOD: Postal questionnaire. RESULTS: 6.2% of the patients had celiac disease. Diabetes was diagnosed at a significantly earlier age in patients with diabetes and celiac disease as compared to those without celiac diasease. Thyroid autoimmunity was reported in 7.6% of cases. They were significantly older with longer duration of diabetes. Every fifth patients reported retinopathy, one sixth of patients was treated for hypertension. Neuropathy was found in 3.4% and kidney disease in 4.8% of the cases. CONCLUSIONS: Apart from retinopathy and hypertension, the prevalence of microvascular complications was relatively low. Considering the limitations of questionnaire studies, laboratory screening is warranted to assess the true prevalence of comorbidities and complications. PMID- 22296927 TI - [The role of FDG PET/CT for detecting the cause of fever of unknown origin in a clinical case]. AB - The fever of unknown origin from time to time constitutes a serious clinical problem and nearly all diagnostic methods are involved to discover urgently its cause. According to literature data (18)F-fluoro-deoxyglucose PET/CT was successful in 25-70% of cases even in patients without any positive findings with conventional diagnostic techniques. The Hungarian National Health Fund does not include fever of unknown origin in the list of reimbursed (18)F-fluoro deoxyglucose PET/CT indications. The authors try to illustrate the clinical problem with this case report. Fever of unknown origin persisted in a patient for a year, but conventional diagnostic procedures were unsuccessful to find the cause of the fever. Finally, (18)F-fluoro-deoxyglucose PET/CT indicated a metabolically active focus between the pancreas tail and the spleen. After a long lasting antibiotic therapy the patient became symptomfree. PMID- 22296928 TI - [The Hungarian Medical Journal 100 years ago]. PMID- 22296929 TI - [The scientific history of the research of the human central nervous system]. PMID- 22296931 TI - How sensitive are estimates of carbon fixation in agricultural models to input data? AB - BACKGROUND: Process based vegetation models are central to understand the hydrological and carbon cycle. To achieve useful results at regional to global scales, such models require various input data from a wide range of earth observations. Since the geographical extent of these datasets varies from local to global scale, data quality and validity is of major interest when they are chosen for use. It is important to assess the effect of different input datasets in terms of quality to model outputs. In this article, we reflect on both: the uncertainty in input data and the reliability of model results. For our case study analysis we selected the Marchfeld region in Austria. We used independent meteorological datasets from the Central Institute for Meteorology and Geodynamics and the European Centre for Medium-Range Weather Forecasts (ECMWF). Land cover / land use information was taken from the GLC2000 and the CORINE 2000 products. RESULTS: For our case study analysis we selected two different process based models: the Environmental Policy Integrated Climate (EPIC) and the Biosphere Energy Transfer Hydrology (BETHY/DLR) model. Both process models show a congruent pattern to changes in input data. The annual variability of NPP reaches 36% for BETHY/DLR and 39% for EPIC when changing major input datasets. However, EPIC is less sensitive to meteorological input data than BETHY/DLR. The ECMWF maximum temperatures show a systematic pattern. Temperatures above 20 degrees C are overestimated, whereas temperatures below 20 degrees C are underestimated, resulting in an overall underestimation of NPP in both models. Besides, BETHY/DLR is sensitive to the choice and accuracy of the land cover product. DISCUSSION: This study shows that the impact of input data uncertainty on modelling results need to be assessed: whenever the models are applied under new conditions, local data should be used for both input and result comparison. PMID- 22296932 TI - Electrophysiological correlates of automatic spreading of activation in patients with psychotic disorder and first-degree relatives. AB - BACKGROUND: Semantic network abnormalities in patients with psychotic disorder were examined using associative prime-target relations with two stimulus asynchronies (SOAs; -250ms and -500ms) to assess the time course of automatic and more controlled processes of semantic priming. To investigate whether an aberrant semantic network system is part of the familial liability for psychosis, healthy siblings of patients with psychotic disorder were additionally examined. The N400 event-related brain potential (ERP) was used as a probe of semantic processing. METHOD: Twenty-two patients with psychotic disorder, twenty siblings of patients with psychotic disorder and twenty controls participated in a lexical decision task and ERPs were recorded to target words that were associatively, indirectly or not related to their preceding prime word. RESULTS: Associative priming of the N400 amplitude was found across all participants and both SOAs, but no between group differences were found for the N400 amplitude (both SOAs). The Group*Condition interaction of the indirect priming N400 latency of the three groups was just short of statistical significance (F2,59=2.7, p=.077). Patients showed an increased indirect priming effect of the N400 latency only at short SOA, with decreased latency of the indirectly related compared to the unrelated condition, while controls did not show an indirect priming N400 latency effect. No between-group differences in N400 latency of indirect priming were found at the long SOA. Only a trend towards a Group*Condition interaction of the indirect priming N400 latency between the sibling and the controls was found, but without a main effect of indirect priming in the sibling group. CONCLUSION: These preliminary results support the assumption of a hyperactive semantic network in patients with psychotic disorder, which develops under automatic processes and decreases with more controlled processes, but does not represent clear trait familial liability. PMID- 22296933 TI - Role of the rumen in copper and thiomolybdate absorption. AB - The rumen is the site of significant interactions between Cu, S and Mo. It also shows reactions between Cu, S and Fe. The interaction between Mo and S results in the formation of thiomolybdates, which in the absence of adequate quantities of rumen Cu are absorbed into the animal and bind to Cu in biological compounds. This is the cause of thiomolybdate toxicity, often misleadingly called Cu deficiency. The effects of thiomolybdates being absorbed into the animal are considered, especially how thiomolybdates bind to Cu-containing compounds such as enzymes, decreasing their activity without removing the active Cu component. The sources of Cu, Mo, Fe and S are examined, including the impacts of water and soil on the animal's intake. Within the present review we have been able to provide evidence that: all classes of thiomolybdates are formed in the rumen; in the absence of available Cu all thiomolybdates can be absorbed into the animal rapidly though the rumen wall or via the small intestine; thiomolybdates bind to Cu in biological compounds and are able to cause problems; effects of thiomolybdate are reversible in vivo and in vitro on cessation of thiomolybdate challenge; the tetra-thiomolybdate form is the most potent Cu binder with decreased potency with decreasing S in the compound. Fe will exacerbate a thiomolybdate problem but will not directly cause it. PMID- 22296934 TI - Human health effects of conjugated linoleic acid from milk and supplements. AB - The primary purpose of the present review was to determine if the scientific evidence available for potential human health benefits of conjugated linoleic acid (CLA) is sufficient to support health claims on foods based on milk naturally enriched with cis-9, trans-11-CLA (c9, t11-CLA). A search of the scientific literature was conducted and showed that almost all the promising research results that have emerged in relation to cancer, heart health, obesity, diabetes and bone health have been in animal models or in vitro. Most human intervention studies have utilised synthetic CLA supplements, usually a 50:50 blend of c9, t11-CLA and trans-10, cis-12-CLA (t10, c12-CLA). Of these studies, the only evidence that is broadly consistent is an effect on body fat and weight reduction. A previous review of the relevant studies found that 3.2 g CLA/d resulted in a modest body fat loss in human subjects of about 0.09 kg/week, but this effect was attributed to the t10, c12-CLA isomer. There is no evidence of a consistent benefit of c9, t11-CLA on any health conditions; and in fact both synthetic isomers, particularly t10, c12-CLA, have been suspected of having pro diabetic effects in individuals who are already at risk of developing diabetes. Four published intervention studies using naturally enriched CLA products were identified; however, the results were inconclusive. This may be partly due to the differences in the concentration of CLA administered in animal and human studies. In conclusion, further substantiation of the scientific evidence relating to CLA and human health benefits are required before health claims can be confirmed. PMID- 22296935 TI - Gait asymmetry: composite scores for mechanical analyses of sprint running. AB - Gait asymmetry analyses are beneficial from clinical, coaching and technology perspectives. Quantifying overall athlete asymmetry would be useful in allowing comparisons between participants, or between asymmetry and other factors, such as sprint running performance. The aim of this study was to develop composite kinematic and kinetic asymmetry scores to quantify athlete asymmetry during maximal speed sprint running. Eight male sprint trained athletes (age 22+/-5 years, mass 74.0+/-8.7 kg and stature 1.79+/-0.07 m) participated in this study. Synchronised sagittal plane kinematic and kinetic data were collected via a CODA motion analysis system, synchronised to two Kistler force plates. Bilateral, lower limb data were collected during the maximal velocity phase of sprint running (velocity=9.05+/-0.37 ms(-1)). Kinematic and kinetic composite asymmetry scores were developed using the previously established symmetry angle for discrete variables associated with successful sprint performance and comparisons of continuous joint power data. Unlike previous studies quantifying gait asymmetry, the scores incorporated intra-limb variability by excluding variables from the composite scores that did not display significantly larger (p<0.05) asymmetry than intra-limb variability. The variables that contributed to the composite scores and the magnitude of asymmetry observed for each measure varied on an individual participant basis. The new composite scores indicated the inter participant differences that exist in asymmetry during sprint running and may serve to allow comparisons between overall athlete asymmetry with other important factors such as performance. PMID- 22296936 TI - Micro CT-based multiscale elasticity of double-porous (pre-cracked) hydroxyapatite granules for regenerative medicine. AB - Hundred micrometers-sized porous hydroxyapatite globules have proved as a successful tissue engineering strategy for bone defects in vivo, as was shown in studies on human mandibles. These granules need to provide enough porous space for bone ingrowth, while maintaining sufficient mechanical competence (stiffness and strength) in this highly load-bearing organ. This double challenge motivates us to scrutinize more deeply the micro- and nanomechanical characteristics of such globules, as to identify possible optimization routes. Therefore, we imaged such a (pre-cracked) granule in a microCT scanner, transformed the attenuation coefficients into voxel-specific nanoporosities, from which we determined, via polycrystal micromechanics, voxel-specific (heterogeneous) elastic properties. The importance of the latter and of the presence of one to several hundred micrometers-sized cracks for realistically estimating the load-carrying behavior of the globule under a typical two-point compressive loading (as in a "splitting" test) is shown through results of large-scale Finite Element analyses, in comparison to analytical results for a sphere loaded at its poles: Use of homogeneous instead of heterogeneous elastic properties would overestimate the structure's stiffness by 5% (when employing a micromechanics-based process as to attain homogeneous properties)-the cracks, in comparison, weaken the structure by one to two orders of magnitudes. PMID- 22296937 TI - [Unusual fetal teratoma presenting as a posterior mediastinal cyst]. AB - Mediastinal cysts are uncommon prenatal findings. As isolated and non-compressing entities, they don't compromise the course of gestation. Massive lesions can compress vital structures, resulting in fetal demise. Thus, close follow-up with sonographic monitoring is recommended until birth. Non-hydroptic fetuses can be managed expectantly. Definitive etiology is known after surgical resection only. We present the first case of posterior mediastinal teratoma associated with severe vertebral abnormalities. After CT scan and fetal MRI, medical termination of pregnancy was decided. Histological examination revealed an immature teratoma. With this unique case report, we discuss the optimal prenatal management of mediastinal cysts. PMID- 22296939 TI - Influence of transportation on serum concentrations of acute phase proteins in horse. AB - The modifications of Haptoglobin (Hp), Serum Amyloid A (SAA), Fibrinogen (Fbg) and White Blood Cells (WBCs) were evaluated in 15 Saddle Italian horses. Ten horses were transported covering a distance of about 320 km within 4 h with an average speed of 80 km/h (experimental group) and five horses were not subject to transportation (control group). Blood was collected via jugular venipuncture before the transportation (T0), immediately after the transportation (T1), 12 (T12), 24 (T24) and 48 (T48)hours after the transportation in experimental group and at the same time point in control group. For each parameter statistical analysis of different groups and sampling time was performed using a two-way analysis of covariance, with the data before the transportation (T0) as the covariate, by the GLM procedure of SAS. For all parameters the interaction (Group * Time) was tested and it was resulted no significant. The application of statistical analysis showed significant differences between the control group and horses subjected to transportation (P<0.01), and the influence of sampling time (P<0.05) on Hp, SAA and WBCs. These modifications appeared to be innovative showing that equine Hp, generally considered as moderate acute phase protein, increases more rapidly than the SAA after transportation-induced stress. PMID- 22296938 TI - Clinical utility of cardiovascular magnetic resonance in hypertrophic cardiomyopathy. AB - Hypertrophic cardiomyopathy (HCM) is characterized by substantial genetic and phenotypic heterogeneity, leading to considerable diversity in clinical course including the most common cause of sudden death in young people and a determinant of heart failure symptoms in patients of any age. Traditionally, two-dimensional echocardiography has been the most reliable method for establishing a clinical diagnosis of HCM. However, cardiovascular magnetic resonance (CMR), with its high spatial resolution and tomographic imaging capability, has emerged as a technique particularly well suited to characterize the diverse phenotypic expression of this complex disease. For example, CMR is often superior to echocardiography for HCM diagnosis, by identifying areas of segmental hypertrophy (ie., anterolateral wall or apex) not reliably visualized by echocardiography (or underestimated in terms of extent). High-risk HCM patient subgroups identified with CMR include those with thin-walled scarred LV apical aneurysms (which prior to CMR imaging in HCM remained largely undetected), end-stage systolic dysfunction, and massive LV hypertrophy. CMR observations also suggest that the cardiomyopathic process in HCM is more diffuse than previously regarded, extending beyond the LV myocardium to include thickening of the right ventricular wall as well as substantial morphologic diversity with regard to papillary muscles and mitral valve. These findings have implications for management strategies in patients undergoing invasive septal reduction therapy. Among HCM family members, CMR has identified unique phenotypic markers of affected genetic status in the absence of LV hypertrophy including: myocardial crypts, elongated mitral valve leaflets and late gadolinium enhancement. The unique capability of contrast-enhanced CMR with late gadolinium enhancement to identify myocardial fibrosis has raised the expectation that this may represent a novel marker, which may enhance risk stratification. At this time, late gadolinium enhancement appears to be an important determinant of adverse LV remodeling associated with systolic dysfunction. However, the predictive significance of LGE for sudden death is incompletely resolved and ultimately future large prospective studies may provide greater insights into this issue. These observations underscore an important role for CMR in the contemporary assessment of patients with HCM, providing important information impacting diagnosis and clinical management strategies. PMID- 22296940 TI - The influence of sex on biochemical markers of bone turnover in dogs. AB - Biochemical markers of bone turnover have been shown to be useful as inexpensive and noninvasive tools for monitoring skeletal health. The reference range for bone markers in dogs has been set by different age groups. However, other sources of biological variations were not fully investigated in dogs. To explore whether sex influences the interpretation of bone marker data we examined serum bone markers in 33 male and 25 female dogs. The bone markers selected for this study were: bone alkaline phosphatase (BALP) and osteocalcin (OC) as indicators of bone formation, and C-terminal telopeptide (CTx) of type I collagen as marker of bone resorption. All concentrations of bone markers were lower, but still within the reference range reported for dogs. We found statistically significant differences of the median OC and CTx serum concentrations between males and females. The results of this study suggest that there are sex differences in biochemical markers of bone turnover in dogs which should be considered in interpretation of bone marker data. PMID- 22296941 TI - Monitoring the reverse to normal of clinico-pathological findings and the disease free interval time using four different treatment protocols for canine leishmaniosis in an endemic area. AB - Twenty-four dogs naturally infected by Leishmania spp. were treated with four different protocols using meglumine antimoniate (aNm) and allopurinol in combination or in monotherapy. Aiming to compare the efficacy of the different treatments the reverse to normal of clinico-pathological findings and the disease free interval time (DFIT) were evaluated. Treated dogs were monitored for 1 year and, in absence of relapses, the DFIT was postponed to the last available follow up. Seven dogs treated with aNm alone showed relapses during the year of observation. In the group of dogs treated with the combination of aNm (50 mg/kg/SC 12 hourly up to clinico-pathological recovery) and allopurinol (15 mg/kg/PO 12 hourly administered for 6months) no relapses were registered in the year of monitoring and the DFIT reached up to 65 months. Our results showed that this combination represents the best choice to treat canine leishmaniosis compared to other protocols. PMID- 22296942 TI - Extra corporeal membrane oxygenation as right heart support following left ventricular assist device placement: a new cannulation technique. AB - Extracorporeal membrane oxygenation is an established treatment for acute respiratory failure, or low cardiac output syndrome. This can be veno-venous, in which de-oxygenated blood is drained from the venous system and oxygenated before being returned to the venous system, and veno-arterial where the re-oxygenated venous blood is returned to the arterial system. Haemorrhage, sepsis and thrombo embolism are common and potentially lethal complications. Left ventricular assist devices are a continually evolving technology, that may be used as a bridge to transplantation or destination therapy in end-stage cardiac failure. The VentrAssistTM left ventricular assist device is a small implantable, continuous flow centrifugal pump, that is controlled and powered by a percutaneous lead. However, in these patients, right heart failure may present as an acute event following weaning from cardiopulmonary bypass (CPB), or post-operatively in the intensive care unit. Patients who do not respond to inotropes and pulmonary vasodilators may need a right ventricular assist device (RVAD). We report a successful case of right heart assist extra corporeal membrane oxygenation used as temporary right heart support in combination with a VentrAssistTM left ventricular assist device. The use of right heart assist extra corporeal membrane oxygenation to help a failing right heart during left ventricular assist device placement is not new, however, our technique describes a novel method of cannulation of the femoral vein and pulmonary trunk via a tunnelled vascular tube graft, which allows the chest to be closed whilst on right heart support, and decannulation to proceed without resternotomy. This technique has also been used successfully subsequent to this. PMID- 22296943 TI - Priming honesty reduces subjective bias in self-report measures of mind wandering. AB - Using self-report as a measure of conscious experience has been a point of contention in mind wandering research. Whereas prior work has focused on the introspective component of self-report validity, the current research introduces an honesty prime task to the current paradigm in order to assess the role of goal states and social factors on self-report accuracy. Findings provide evidence for an inflated report of mind wandering frequency arising from demand characteristics, intensified by the divergent properties of the subjective and behavioural measures and the general deficit in meta-awareness of off task episodes. PMID- 22296944 TI - Fechner as a pioneering theorist of unconscious cognition. AB - Fechner remains virtually unknown for his psychological research on the unconscious. However, he was one of the most prominent theorists of unconscious cognition of the 19th century, in the context of the rise of scientific investigations on the unconscious in German psychology. In line with the models previously developed by Leibniz and Herbart, Fechner proposes an explanative system of unconscious phenomena based on a modular conception of the mind and on the idea of a functional dissociation between representational and attentional activity. For Fechner, the unconscious is a state of consciousness resulting from the isolation of representational activity from the rest of psychical life. Unconscious mental phenomena are unattended mental states that behave autonomously while remaining able to act on consciousness. This paper aims to revisit Fechner's contribution to the history of the unconscious, but also the theoretical significance of the Fechnerian unconscious vis-a-vis current research on the cognitive unconscious. PMID- 22296945 TI - Cognitive and brain changes associated with ischaemic heart disease and heart failure. AB - AIMS: It is unclear whether the cognitive dysfunction associated with heart failure (HF) is due to HF or comorbid conditions such as ischaemic heart disease (IHD). This study aimed to determine whether, compared with controls with and without IHD, adults with systolic HF show evidence of cognitive impairment and cerebral grey matter (GM) loss. METHODS AND RESULTS: Cross-sectional study of 35 participants with HF, 56 with IHD, and 64 controls without either HF or IHD. Subjects were older than 45 years and free of overt cognitive impairment. We acquired magnetic resonance images and used SPM8 to determine regional differences in cerebral GM volume. Participants with HF had lower scores than controls without IHD on immediate memory, long delay recall and digit coding, whereas those with IHD had lower long delay recall scores than controls without IHD. Compared with controls without IHD, participants with HF showed evidence of GM loss in the left cingulate, the right inferior frontal gyrus, the left middle and superior frontal gyri, the right middle temporal lobe, the right and left anterior cingulate, the right middle frontal gyrus, the inferior and pre-central frontal gyri, the right caudate, and occipital-parietal regions involving the left precuneus. The loss of GM followed a similar, less extensive, pattern when we compared participants with HF and IHD. CONCLUSION: Adults with HF have worse immediate and long-term memory and psychomotor speed than controls without IHD. Heart failure is associated with changes in brain regions that are important for demanding cognitive and emotional processing. PMID- 22296946 TI - Long-term persistence with the immunomodulatory drugs for multiple sclerosis: a retrospective database study. AB - BACKGROUND: Immunomodulatory drugs (IMDs) for multiple sclerosis (MS) have been available in Canada since 1995 and are currently the most commonly prescribed treatment for MS. However, relatively little is known about the long-term persistence to these drugs. OBJECTIVE: The purpose of this study was to describe patterns of, and factors associated with, long-term persistence to the first-line IMDs in an MS population in British Columbia, Canada. METHODS: Study data were collected from the British Columbia MS database. Adults from British Columbia with definite MS who were prescribed a first-line IMD (interferon beta-1b, interferon beta-1a [subcutaneous and intramuscular], and glatiramer acetate) from January 1, 1995, through December 31, 2008, were eligible for the study. Time to discontinuation of use of all first-line IMDs (ie, switching among IMD therapies was allowed) and the initially prescribed IMD was assessed using Kaplan-Meier survival analysis and multivariate Cox regression. RESULTS: A total of 1896 patients were included. Mean (SD) age was 40.2 (9.5) years, and 75.1% were female. Median time to discontinuation of all first-line IMD therapies was 6.3 years (95% CI, 5.8-6.7 years). Patients with a longer disease duration and higher level of disability were at higher risk for discontinuing use of the IMDs. Age, sex, and the initial IMD were not associated with discontinuation. Persistence appeared to have decreased over time (P = 0.01 for trend). Median time to discontinued use of, or switching from, the initially prescribed IMD was 2.9 years (95% CI, 2.5-3.2 years). CONCLUSIONS: Approximately half of the MS patients discontinued use of their IMD within 6 years. It is unknown whether this persistence is adequate because uncertainties remain regarding the optimal level of persistence to the IMDs. Further investigation is needed to examine why some individuals are more at risk for discontinuation of IMD therapy and why, in contrast to other chronic diseases, persistence to IMDs in patients with MS has not improved over time. PMID- 22296947 TI - A network meta-analysis on the efficacy of serotonin type 3 receptor antagonists used in adults during the first 24 hours for postoperative nausea and vomiting prophylaxis. AB - BACKGROUND: The serotonin type 3 receptor antagonists (5-HT(3) antagonists) ondansetron, granisetron, tropisetron, and dolasetron are potential prophylactic agents for patients with mild to moderate risk of postoperative nausea and vomiting (PONV). A few trials have been conducted to compare the efficacy among 2 to 3 of these 4 agents. However, the comparative efficacy of all four 5-HT(3) antagonists has not yet been quantitatively investigated. OBJECTIVE: The goal of this study was to investigate whether the 5-HT(3) antagonists--ondansetron, granisetron, tropisetron, and dolasetron-differ in efficacy when used for the prevention of PONV. METHODS: PubMed and the Cochrane Library were searched for randomized controlled, double-blind studies measuring efficacy in terms of PONV prophylaxis. A Bayesian meta-analysis was conducted using published studies of 5 HT(3) antagonists for PONV prophylaxis. The odds of patients with no PONV and postoperative vomiting (POV) within each study arm 24 hours after surgery were the primary indices of drug efficacy. Data were extracted and analyzed via indirect comparisons using random effects Bayesian models in WinBUGS version 1.4.3. RESULTS: A total of 85 studies were identified, representing 15,269 patients. The results indicate that granisetron was significantly better than ondansetron (odds ratio [OR] = 1.53 [95% credible interval (CI), 1.15-2.00]) and dolasetron (OR = 1.67 [95% CI, 1.12-2.38]) in preventing PONV. Four antiemetic drugs had comparable efficacy in terms of preventing POV: granisetron showed similar efficacy compared with ondansetron (OR = 1.49 [95% CI, 0.90-2.43]), tropisetron (OR = 1.69 [95% CI, 0.92-3.13]), and dolasetron (OR = 1.32 [95% CI, 0.71-2.38]). Ondansetron exhibited comparable efficacy compared with tropisetron (OR = 1.14 [95% CI, 0.66-1.96]) and dolasetron (OR = 0.88 [95% CI, 0.51-1.47]). Tropisetron and dolasetron were also similar in efficacy (OR = 0.78 [95% CI, 0.40 1.45]). All 5-HT(3) antagonists were statistically significantly better at preventing PONV or POV than placebo. CONCLUSIONS: With respect to PONV prophylaxis, granisetron was significantly better than ondansetron and dolasetron; ondansetron, tropisetron, and dolasetron exhibited similar efficacy. With respect to POV prophylaxis, ondansetron, granisetron, tropisetron, and dolasetron seemed to have comparable efficacy. PMID- 22296948 TI - Risk of haemorrhagic and ischaemic stroke in patients with cancer: a nationwide follow-up study from Sweden. AB - BACKGROUND: Stroke is common in cancer patients, but risk estimates for different cancer sites/types have not been determined. The aim of this nationwide study was to examine whether there is an association between cancer and first hospitalisation for haemorrhagic or ischaemic stroke. METHODS: All 820,491 individuals in Sweden with a diagnosis of cancer between 1st January 1987 and 31st December 2008 were followed for first hospitalisation for haemorrhagic or ischaemic stroke. The reference population was the total population of Sweden without cancer. Standardised incidence ratios (SIRs) for haemorrhagic and ischaemic strokes were calculated. RESULTS: Overall risk of haemorrhagic stroke and ischaemic stroke during the first 6 months after diagnosis of cancer was 2.2 (95% confidence interval (CI)= 2.0-2.3) and 1.6 (CI = 1.5-1.6), respectively. For 18 and 20 of the 34 cancers studied, respectively, risk of haemorrhagic and ischaemic strokes was increased. Overall stroke risk decreased rapidly, but remained elevated, even 10+years after diagnosis of cancer 1.2 (CI = 1.1-1.3) for haemorrhagic stroke and 1.1 (CI = 1.1-1.2) for ischaemic stroke. The risk of stroke was highest during the first 6 months after diagnosis of cancer of the nervous system (29 (CI = 25-34) for haemorrhagic stroke and 4.1 (CI = 3.4-4.8) for ischaemic stroke)) or leukaemia (13 (CI = 10-16) for haemorrhagic stroke and 3.0 (CI = 2.5-3.7) for ischaemic stroke)). Metastasis was associated with an increased risk of haemorrhagic stroke 2.2 (CI = 1.8-2.7) and ischaemic stroke 1.5 (CI = 1.3-1.7). INTERPRETATION: Several cancer sites/types are associated with an increased risk of haemorrhagic and ischaemic strokes. PMID- 22296949 TI - A 'beautiful death': mortality, death, and holidays in a Mexican municipality. AB - Several studies have reported increased mortality during holidays. Using a cultural epidemiological, sequential mixed-methods approach, this study explored holiday-related trends using mortality data from Yautepec (Morelos, Mexico) collected between 1986 and 2008 (N=5027 deaths). This analysis found that mortality increased on Christmas Day and All Saints' Day. Mortality increased on Candlemas Day among women, and increased on New Year's Day among men. More deaths caused by cardiovascular disease among women and traumatic injuries among men occurred during holidays than in non-holiday periods. To ascertain the elements comprising the health/illness/death process in the context of a holiday in this municipality, we conducted semi-structured interviews in March and April 2009 with relatives of seven individuals who had died during holidays in the previous 4 years (N=11); data from these interviews were analyzed from a grounded theory perspective to ascertain common conceptual themes. The "beautiful death" emerged as the main concept in the interpretation of death; this concept was related to the expectation of a good death and the particularly special nature of death during a holiday because of the involvement of religious entities, such as God, the Virgin Mary, and/or a saint, at the moment of death. Quantitative and qualitative results provided information about the important effects of holidays, culture, and religious belief on mortality patterns within a Mexican context, and contributed to a better understanding of the relationships among mortality, the nature of death, and holidays. Our results suggest that, in the studied region, death can be interpreted as a "beautiful process". More research is needed to explore this process in other similar contexts and to address topics related to the care and attention given the dying person and the expectation of a good death. PMID- 22296950 TI - Effectiveness of a multidisciplinary care program on recovery and return to work of patients after gynaecological surgery; design of a randomized controlled trial. AB - BACKGROUND: Return to work after gynaecological surgery takes much longer than expected, irrespective of the level of invasiveness. In order to empower patients in recovery and return to work, a multidisciplinary care program consisting of an e-health intervention and integrated care management including participatory workplace intervention was developed. METHODS/DESIGN: We designed a randomized controlled trial to assess the effect of the multidisciplinary care program on full sustainable return to work in patients after gynaecological surgery, compared to usual clinical care. Two hundred twelve women (18-65 years old) undergoing hysterectomy and/or laparoscopic adnexal surgery on benign indication in one of the 7 participating (university) hospitals in the Netherlands are expected to take part in this study at baseline. The primary outcome measure is sick leave duration until full sustainable return to work and is measured by a monthly calendar of sickness absence during 26 weeks after surgery. Secondary outcome measures are the effect of the care program on general recovery, quality of life, pain intensity and complications, and are assessed using questionnaires at baseline, 2, 6, 12 and 26 weeks after surgery. DISCUSSION: The discrepancy between expected physical recovery and actual return to work after gynaecological surgery contributes to the relevance of this study. There is strong evidence that long periods of sick leave can result in work disability, poorer general health and increased risk of mental health problems. We expect that this multidisciplinary care program will improve peri-operative care, contribute to a faster return to work of patients after gynaecological surgery and, as a consequence, will reduce societal costs considerably. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR2087. PMID- 22296951 TI - Dialysis access. AB - Although hemodialysis access procedures are considered the most common vascular procedures performed by either general or vascular surgeons, there is a paucity of level-one evidence in the literature. Randomized controlled trials are limited, and most of these studies have small sample sizes compared with other areas of vascular surgery, that is, carotid or aneurysm studies. We summarize the results of the world's literature for arteriovenous access in table format as a tool for those specialists managing patients with arteriovenous access procedures. PMID- 22296952 TI - Hypothermic cardiac arrest far away from the center providing rewarming with extracorporeal circulation. AB - A 41-year-old man suffered hypothermic cardiac arrest after water immersion and was transported to our university hospital by ambulance helicopter for rewarming on cardiopulmonary bypass. He resumed spontaneous cardiac activity 6 h 52 min after cardiac arrest and recovered completely. PMID- 22296953 TI - Does healthcare infrastructure have an impact on delay in diagnosis and survival? AB - INTRODUCTION: The objectives of this study were to evaluate whether healthcare infrastructure impacts delay in diagnosis, and to determine whether healthcare infrastructure and delay in diagnosis impacts survival in gastric cancer. METHODS: Administrative data from 2175 gastric cancer patients was analyzed using two Cox proportional hazard models with (i) delay in diagnosis and (ii) survival as dependent variables. Density of general practitioners, density of gastroenterologists, characteristics of specialty treatment centers, demographic information, and comorbidities were included in the models. Differentiation was made between urban and rural areas. RESULTS: The likelihood of being diagnosed increased with an increase in general practitioners (p<0.0001) and gastroenterologists (p<0.0001) in rural areas. In urban areas a higher density of general practitioners reduced delay in diagnosis (p=0.0262), while a higher density of gastroenterologists did not (p=0.2480). The number of gastric cancer cases performed in hospital had a positive impact on survival (p<0.0001), while outpatient infrastructure did not. CONCLUSION: Delay in diagnosis can be reduced by higher availability of general practitioners and gastroenterologists in rural areas. Given the already very high density of physicians in urban areas there is no effect of additional gastroenterologists. As learning effects can be observed with increased hospital volumes, minimum volumes for treatment of gastric cancer may be defined. PMID- 22296954 TI - Long-term efficacy of 10-12 years after being immunized with Chinese hamster ovary cell derived hepatitis B vaccine in Chinese Rural Communities. AB - OBJECTIVE: To evaluate the long-term efficacy of Chinese hamster ovary (CHO) cell derived hepatitis B vaccine in country community in China. METHODS: A cross sectional investigation was carried out. Children who were born between 1997 and 1999 and vaccinated with the three doses of CHO-derived hepatitis B vaccine were selected as study objects. Their serum samples were taken to test for hepatitis B virus (HBV) markers, and the results were compared to that before vaccination. In addition, for HBsAg positive children, their mothers were visited. RESULTS: 1254 Children were enrolled in the study. The prevalence of HBsAg was 0.24% and the vaccine efficacy was 97.0%, similar to that of yeast derived hepatitis vaccines. Among 3 mothers of HBsAg positive children, 2 were HBsAg positive, indicating maternal HBV transmissions. CONCLUSION: The long-term efficacy of the CHO-derived hepatitis B vaccine is good and after vaccination maternal transmission is the most important route of spreading HBV. PMID- 22296955 TI - A recombinant adenovirus expressing immunodominant TB antigens can significantly enhance BCG-induced human immunity. AB - BACKGROUND: Despite the availability of Bacille Calmette Guerin (BCG) vaccines, Mycobacterium tuberculosis currently infects billions of people and millions die annually from tuberculosis (TB) disease. New TB vaccines are urgently needed. METHODS: We studied the ability of AERAS-402, a recombinant, replication deficient adenovirus type 35 expressing the protective M. tuberculosis antigens Ag85A, Ag85B, and TB10.4, to boost BCG immunity in an area of low TB endemicity. RESULTS: In volunteers primed with BCG 3 or 6 months prior to AERAS-402 boosting, significant CD4(+) and CD8(+) T cell responses were induced. Ag85-specific responses were more strongly boosted than TB10.4-specific responses. Frequencies of TB-specific CD8(+) T cells reached>50 fold higher than pre-AERAS boosting levels, remarkably higher than reported in any previous human TB vaccine trial. Multiparameter flow cytometric assays demonstrated that AERAS-402-boosted CD4(+) and CD8(+) T cells were multifunctional, producing multiple cytokines and other immune effector molecules. Furthermore, boosted T cells displayed lymphoproliferative capacity, and tetramer analyses confirmed that antigen specific CD8(+) T cells were induced. BCG and AERAS-402 vaccinations given 3 and 6 months apart appeared equivalent. CONCLUSIONS: Our results indicate that AERAS 402 is a promising TB vaccine candidate that can significantly enhance both CD4(+) and CD8(+) TB-specific T cell responses after BCG priming. ClinicalTrials.gov Identifier: NCT01378312. PMID- 22296956 TI - Zonation related function and ubiquitination regulation in human hepatocellular carcinoma cells in dynamic vs. static culture conditions. AB - BACKGROUND: Understanding hepatic zonation is important both for liver physiology and pathology. There is currently no effective systemic chemotherapy for human hepatocellular carcinoma (HCC) and its pathogenesis is of special interest. Genomic and proteomic data of HCC cells in different culture models, coupled to pathway-based analysis, can help identify HCC-related gene and pathway dysfunctions. RESULTS: We identified zonation-related expression profiles contributing to selective phenotypes of HCC, by integrating relevant experimental observations through gene set enrichment analysis (GSEA). Analysis was based on gene and protein expression data measured on a human HCC cell line (HepG2/C3A) in two culture conditions: dynamic microfluidic biochips and static Petri dishes. Metabolic activity (HCC-related cytochromes P450) and genetic information processing were dominant in the dynamic cultures, in contrast to kinase signaling and cancer-specific profiles in static cultures. That, together with analysis of the published literature, leads us to propose that biochips culture conditions induce a periportal-like hepatocyte phenotype while standard plates cultures are more representative of a perivenous-like phenotype. Both proteomic data and GSEA results further reveal distinct ubiquitin-mediated protein regulation in the two culture conditions. CONCLUSIONS: Pathways analysis, using gene and protein expression data from two cell culture models, confirmed specific human HCC phenotypes with regard to CYPs and kinases, and revealed a zonation-related pattern of expression. Ubiquitin-mediated regulation mechanism gives plausible explanations of our findings. Altogether, our results suggest that strategies aimed at inhibiting activated kinases and signaling pathways may lead to enhanced metabolism-mediated drug resistance of treated tumors. If that were the case, mitigating inhibition or targeting inactive forms of kinases would be an alternative. PMID- 22296957 TI - 3'-axial CH2 OH substitution on glucopyranose does not increase glycogen phosphorylase inhibitory potency. QM/MM-PBSA calculations suggest why. AB - Glycogen phosphorylase is a molecular target for the design of potential hypoglycemic agents. Structure-based design pinpointed that the 3'-position of glucopyranose equipped with a suitable group has the potential to form interactions with enzyme's cofactor, pyridoxal 5'-phosphate (PLP), thus enhancing the inhibitory potency. Hence, we have investigated the binding of two ligands, 1 (beta-d-glucopyranosyl)5-fluorouracil (GlcFU) and its 3'-CH(2) OH glucopyranose derivative. Both ligands were found to be low micromolar inhibitors with K(i) values of 7.9 and 27.1 MUm, respectively. X-ray crystallography revealed that the 3'-CH(2) OH glucopyranose substituent is indeed involved in additional molecular interactions with the PLP gamma-phosphate compared with GlcFU. However, it is 3.4 times less potent. To elucidate this discovery, docking followed by postdocking Quantum Mechanics/Molecular Mechanics - Poisson-Boltzmann Surface Area (QM/MM PBSA) binding affinity calculations were performed. While the docking predictions failed to reflect the kinetic results, the QM/MM-PBSA revealed that the desolvation energy cost for binding of the 3'-CH(2) OH-substituted glucopyranose derivative out-weigh the enthalpy gains from the extra contacts formed. The benefits of performing postdocking calculations employing a more accurate solvation model and the QM/MM-PBSA methodology in lead optimization are therefore highlighted, specifically when the role of a highly polar/charged binding interface is significant. PMID- 22296958 TI - The effects of low-dose methamphetamine pretreatment on endoplasmic reticulum stress and methamphetamine neurotoxicity in the rat midbrain. AB - Methamphetamine (METH) neurotoxicity is involved in METH-related deaths. It has been suggested that the midbrain, together with the striatum, is affected by METH neurotoxicity and the endoplasmic reticulum (ER) stress is induced in the processes of METH neurotoxicity. In this study, we examined the effects of low dose METH administration for 5d on GRP78 and C/EBP homologous protein (CHOP), both of which are induced under ER stress, and METH neurotoxicity in the rat midbrain. We showed that 1mg/kg of METH induced an increase in GRP78 protein and mRNA expression 1d after the last injection, but had no effect on the levels of CHOP, tyrosine hydroxylase (TH), or GFAP. Secondly, we evaluated the induction of ER stress and the extent of METH neurotoxicity in the midbrain of animals pretreated with METH. In animals pretreated with saline, we observed elevated CHOP levels, together with decreased TH levels and increased GFAP levels, indicative of METH neurotoxicity, after neurotoxic METH administration, while there was no significant change in GRP78 levels. In contrast, low-dose METH (1.0mg/kg) pretreatment increased GRP78 levels and inhibited the induction of CHOP in the midbrain without METH neurotoxicity. These findings of ER stress in animals pretreated with METH were associated with an early increase in SOD1 levels and upregulation of Bcl-2. Therefore, our study suggests that pretreatment with low-dose METH may be protective against METH neurotoxicity in the midbrain, leading to the suppression of oxidative stress and apoptotic mechanisms, in part via ER stress-related pathways. Because chronic human METH abusers administrate low-dose METH repeatedly over an extended period before lethal injection, investigation of the pathophysiology of METH neurotoxicity in animals pretreated with low-dose METH might provide useful information on the pathophysiology of chronic and/or lethal METH use in cases of METH-related deaths. PMID- 22296959 TI - Ten years of antipsychotic prescribing to children: a Canadian population-based study. AB - OBJECTIVE: To report the prescribing of antipsychotics to the youth population of the Canadian province of Manitoba during the course of a decade. METHODS: Use of antipsychotics in children and adolescents (aged 18 years or younger) was described using data collected from the administrative health databases of Manitoba Health and the Statistics Canada census between the fiscal years of 1999 and 2008. RESULTS: The prevalence of antipsychotic use in this segment of the population increased with the introduction of the second-generation antipsychotics (SGAs) from 1.9 per 1000 in 1999 to 7.4 per 1000 in 2008. The male to-female antipsychotic usage ratio increased from 1.9 to 2.7 as the male youth population represented the fastest-growing subgroup of antipsychotic users in the entire population of Manitoba. The total number of prescriptions also increased significantly despite the lack of approved indications in this population. Proportion of use remained equally split between high- and low-income users. More than 70% of antipsychotic prescriptions to children and adolescents were written by general practitioners. The most common diagnoses linked to antipsychotic use were attention-deficit hyperactivity disorder and conduct disorders. Use of antipsychotics in combination with methylphenidate increased from 13% to 43%. CONCLUSION: Extensive off-label use of SGAs has been observed in the youth population of Manitoba for treatment of aggressive behaviours across a range of diagnoses. It is important to monitor antipsychotic prescribing to children as more reports of significant adverse events associated with antipsychotics become available. PMID- 22296961 TI - Obesity and mental health--a complicated and complex relation. PMID- 22296962 TI - Beyond pharmacotherapy: understanding the links between obesity and chronic mental illness. AB - While differences in weight-gain potential exist, both between and within classes of psychiatry medications, most commonly used atypical antipsychotics, mood stabilizers, and antidepressants result in some degree of weight gain. This is not new information and it requires an understanding of the tolerability profiles of different treatments and their goodness of fit with specific patient phenotypes. However, this iatrogenic association represents only a piece of this obesity-mental illness dyad. The complex interplay between psychiatric illness and weight involves neurobiology, psychology, and sociological factors. Parsing the salient variables in people with mental illness is an urgent need insofar as mortality from physical health causes is the most common cause of premature mortality in people with chronic mental illness. Our review examines issues associated with common chronic mental illnesses that may underlie this association and warrant further study if we hope to clinically intervene to control this life-threatening comorbidity. PMID- 22296963 TI - An overview of treatments for obesity in a population with mental illness. AB - Obesity is associated with early mortality and has overtaken smoking as the health problem with the greatest impact on quality of life, mortality, and morbidity. Despite public health initiatives and numerous commercial enterprises focusing on weight loss, obesity rates continue to rise. In part, this is because obesity is a multifaceted, complex illness, impacted by numerous social, psychological, and behavioural factors that are unrecognized in most current initiatives. One significant factor associated with obesity is mental illness. While having a psychiatric illness does not make weight gain inevitable, it does often require that additional tools be added to lifestyle recommendations around diet and exercise. The following article reviews the common approaches to obesity management and addresses how these strategies can be implemented in psychiatric care. It is important that health professionals involved in the care of people with a mental illness become familiar with the interventions available to control and treat the obesity epidemic, as this will improve treatment compliance and ultimately lead to improved physical and psychological outcomes. PMID- 22296964 TI - Emergency department assessment of self-harm risk using psychometric questionnaires. AB - OBJECTIVE: To examine several potential predictive screening tools for emergency department assessment of risk of self-harm. METHODS: Adult patients presenting with self-harm or suicidal ideation were enrolled at 2 emergency departments at large teaching hospitals in Edmonton, Alberta. Patients completed a brief interview assessing demographics and psychiatric history and several questionnaires (the Beck Hopelessness Scale, the Barrett Impulsiveness Scale [BIS], and the Brief Symptom Inventory [BSI]) and drug and alcohol abuse screens (Drug Abuse Screening Test [DAST-10] and the Cut down, Annoyed, Guilt, Eye-opener [commonly referred to as CAGE] Questionnaire). At 3 months, patients were followed up via telephone and electronic health records to ascertain self-harm outcome. Questionnaires and their subscales were assessed using logistic regression. Receiver operating characteristic (ROC) analysis was performed on the results. RESULTS: Among the 157 patients enrolled, 49% were women and 36% (of the total) were aged 18 to 29 years. Several of the subscales of the BSI and BIS as well as the DAST-10 were significant predictors of self-harm (P < 0.05). ROC analysis showed that none of the scales in isolation were very strong predictors. Hierarchical regression analysis that combined the significant scales with clinical risk factors that were significantly related to self-harm (that is, age, education level, history of self-harm, and whether they presented with self-harm or only suicidal ideation) indicated that the BIS and DAST-10 questionnaires each added significantly to the predictive ability of a model with these risk factors. CONCLUSIONS: While many of the questionnaires and their related constructs are related to future self-harm, none of them are particularly strong and their diagnostic usefulness is limited. PMID- 22296965 TI - Wait time impact of co-located primary care mental health services: the effect of adding collaborative care in northern Ontario. AB - OBJECTIVES: In the shared care model, psychiatrists and physicians work in the same office areas, write their notes in the same casebooks, and can more rapidly exchange information about referrals and health conditions of their patients. We evaluated the impact of the introduction of a shared mental health care service, co-located with a primary care site, on wait times for mental health services in a northern Ontario city. METHOD: Chart reviews were conducted to examine a total of 3589 referrals for 5 mental health outpatient services (1 shared care and 4 existing services) from January 2001 to the end of June 2004. The shared mental health care service site was started in July 2001. Wait time was measured 6 months prior to and up to 3 years after the introduction of the shared care service. RESULTS: The shared care site offered services more than 40 days sooner and also helped to reduce wait time on the nonshared care sites. After shared care began, the pre-existing, nonshared care services had wait times of about 13 days shorter during the 3 subsequent years. CONCLUSIONS: The shared care service maintained the lowest overall wait times, compared with the existing nonshared care services. The existing services experienced a decrease in the number of days waiting when the baseline wait time was compared with that of the following year. PMID- 22296966 TI - Waist circumference is a sensitive screening tool for assessment of metabolic syndrome risk in children treated with second-generation antipsychotics. AB - OBJECTIVE: To compare the prevalence of metabolic syndrome (MetS) and its components in second-generation antipsychotic (SGA)-treated and SGA-naive children; and to explore the utility of clinical markers, such as waist circumference (WC) and body mass index (BMI), as screening tools for MetS. METHODS: Subjects were prospectively recruited from the Psychiatry Emergency Unit at British Columbia Children's Hospital. As part of a quality-assurance project, a metabolic monitoring protocol was implemented, including collection of anthropomorphic and laboratory data. RESULTS: From January 2008 to February 2010, there were 117 SGA-treated and 217 SGA-naive children recruited. The overall prevalence of MetS was 19.0% (16/84; median treatment duration = 14 months) in SGA-treated and 0.8% (1/127) in SGA-naive children (OR 29.7; 95% CI 3.85 to 228.40, P < 0.001), with an increased prevalence of all components except high density lipoprotein cholesterol (HDL-C), respectively: elevated WC (40.7% and 10.1%; P < 0.001); hypertriglyceridemia (33.7% and 18.8%; P = 0.01); impaired fasting glucose (12.5% and 0.7%; P = 0.005); and elevated blood pressure (41.2% and 16.5%; P < 0.001). SGA treatment was the strongest predictor of MetS (OR 19.2; 95% CI 2.30 to 160.44, P = 0.006) followed by male sex (OR 5.7; 95% CI 1.08 to 30.62, P = 0.04). Presence of abdominal obesity was more sensitive (92.9%) than BMI (68.8%), while fasting glucose of 5.6 mmol/L or more and HDL-C of 1.03 mmol/L or less were most specific (94.1%) in correctly identifying MetS. CONCLUSIONS: SGA treatment confers a significantly increased risk for MetS over the long term. WC measurement is a simple and sensitive screening tool for determining MetS risk in SGA-treated children. These data highlight the dangers of SGA treatment and the importance of standardized metabolic monitoring using sex- and age-adjusted tables in this population. PMID- 22296967 TI - Parental sexual abuse and suicidal behaviour among women with major depressive disorder. AB - OBJECTIVE: Women with major depressive disorder (MDD) and childhood sexual abuse histories have an increased risk for suicidal behaviours, but it is unclear whether specific abuse characteristics contribute to risk. We aimed to examine the contributions of abuse characteristics to lifetime history of suicide attempts and multiple suicide attempts, independent of posttraumatic stress disorder and borderline personality disorder. METHOD: Women with MDD and sexual abuse histories (n = 106) were assessed regarding sexual abuse characteristics, psychiatric diagnoses, and suicide attempts. RESULTS: In multivariate logistic regressions, the odds of having multiple suicide attempts increased 12.27-fold when childhood sexual abuse was perpetrated by a parent figure or a parent, compared with a nonparent. CONCLUSIONS: Parental perpetration of sexual abuse increases the likelihood of multiple suicide attempts among women outpatients. The relationship of the perpetrator to the abused woman is important in suicide risk evaluation and treatment planning. CLINICAL TRIAL REGISTRATION NUMBER: NCT00843700. PMID- 22296968 TI - Structural, optical, and magnetic studies of manganese-doped zinc oxide hierarchical microspheres by self-assembly of nanoparticles. AB - In this study, a series of manganese [Mn]-doped zinc oxide [ZnO] hierarchical microspheres [HMSs] are prepared by hydrothermal method only using zinc acetate and manganese acetate as precursors and ethylene glycol as solvent. X-ray diffraction indicates that all of the as-obtained samples including the highest Mn (7 mol%) in the crystal lattice of ZnO have a pure phase (hexagonal wurtzite structure). A broad Raman spectrum from as-synthesized doping samples ranges from 500 to 600 cm-1, revealing the successful doping of paramagnetic Mn2+ ions in the host ZnO. Optical absorption analysis of the samples exhibits a blueshift in the absorption band edge with increasing dopant concentration, and corresponding photoluminescence spectra show that Mn doping suppresses both near-band edge UV emission and defect-related blue emission. In particular, magnetic measurements confirm robust room-temperature ferromagnetic behavior with a high Curie temperature exceeding 400 K, signifying that the as-formed Mn-doped ZnO HMSs will have immense potential in spintronic devices and spin-based electronic technologies. PMID- 22296969 TI - Are there lessons to be learned from a more scientific approach to mental condition defences? AB - The timing of the English Law Commission's consideration of reform to the law of insanity coincides with increasing scientific and in particular neuroscientific understanding of the brain. The work of researchers is leading to a greater comprehension of what had been termed irresistible impulses to commit crime and of the impact of brain damage, particularly evidence of brain lesions and frontal lobe damage on behaviour. There remain problems in establishing causal relationships which might diminish or eliminate criminal responsibility for crimes committed by those suffering from pre existing mental conditions at the time they commit a criminal offence. This is especially the case where those mental conditions are of short duration. However, the law should not ignore the best available scientific knowledge. Neuroscientific advances are already informing court deliberations in England and Wales: assisting in considerations of guilt, fitness to plead and in sentencing. In terms of the insanity defence the questions that the law seeks to address are not necessarily the most medically or scientifically pertinent questions. They remain grounded in 19th century scientific understanding. It is argued that the more nuanced Dutch approach to mental condition defences warrants very serious consideration by those charged with making proposals to reform the English law. PMID- 22296970 TI - Binary VOCs absorption in a rotating packed bed with blade packings. AB - This investigation addressed the mass transfer of rotating packed beds with blade packings in removing methanol and 1-butanol from binary mixtures by absorption using water as the absorbent. The dependences of the overall volumetric gas-phase mass transfer coefficient (K(G)a) on the inlet methanol concentration, the inlet 1-butanol concentration, the rotational speed, the gas flow rate, and the liquid flow rate, were explored. The results demonstrated that the inlet methanol and 1 butanol concentrations had a negligible effect on the K(G)a values of methanol and 1-butanol. The K(G)a values of methanol and 1-butanol increased with the rotational speed, the gas flow rate, and the liquid flow rate. The dependence of K(G)a on the gas flow rate was higher than that on the liquid flow rate, revealing that the mass transfer in binary VOCs absorption may be controlled considerably by the mass transfer in gas phase. PMID- 22296971 TI - Nurr1 regulates Top IIbeta and functions in axon genesis of mesencephalic dopaminergic neurons. AB - BACKGROUND: NURR1 (also named as NR4A2) is a member of the steroid/thyroid hormone receptor family, which can bind to DNA and modulate expression of target genes. Previous studies have shown that NURR1 is essential for the nigral dopaminergic neuron phenotype and function maintenance, and the defects of the gene are possibly associated with Parkinson's disease (PD). RESULTS: In this study, we used new born Nurr1 knock-out mice combined with Affymetrix genechip technology and real time polymerase chain reaction (PCR) to identify Nurr1 regulated genes, which led to the discovery of several transcripts differentially expressed in the nigro-striatal pathway of Nurr1 knock-out mice. We found that an axon genesis gene called Topoisomerase IIbeta (Top IIbeta) was down-regulated in Nurr1 knock-out mice and we identified two functional NURR1 binding sites in the proximal Top IIbeta promoter. While in Top IIbeta null mice, we saw a significant loss of dopaminergic neurons in the substantial nigra and lack of neurites along the nigro-striatal pathway. Using specific TOP II antagonist ICRF-193 or Top IIbeta siRNA in the primary cultures of ventral mesencephalic (VM) neurons, we documented that suppression of TOP IIbeta expression resulted in VM neurites shortening and growth cones collapsing. Furthermore, microinjection of ICRF-193 into the mouse medial forebrain bundle (MFB) led to the loss of nigro-striatal projection. CONCLUSION: Taken together, our findings suggest that Top IIbeta might be a down-stream target of Nurr1, which might influence the processes of axon genesis in dopaminergic neurons via the regulation of TOP IIbeta expression. The Nurr1-Top IIbeta interaction may shed light on the pathologic role of Nurr1 defect in the nigro-striatal pathway deficiency associated with PD. PMID- 22296972 TI - Targeted gonadotrophin stimulation using the PIVET algorithm markedly reduces the risk of OHSS. AB - PIVET Medical Centre has developed an empirical algorithm for the dose of FSH administration based upon day-2 FSH, antral follicle count, anti-Mullerian hormone, body mass index, age and smoking parameters in an attempt to reduce the incidence of ovarian hyperstimulation syndrome particularly in at-risk women with elevated antral follicle count and anti-Mullerian hormone. The algorithm utilized the incremental dosage capabilities of the recombinant FSH pens to fine-tune the daily concentration of FSH. Application of the algorithm aimed to minimize any form of excessive follicle recruitment that necessitated increased clinical awareness. The measure used to assess the impact of the algorithm was the number of women who, after oocyte retrieval, were considered to be potentially at risk of any degree of OHSS and were allocated to increased monitoring. Compared with the previous 20-month period, introduction of the algorithm significantly reduced both the incidence of referral for increased monitoring, treatment for OHSS and the incidence of freeze-all cycles (all P < 0.05). This was particularly focused on those considered to be at risk without reducing the fresh cycle pregnancy rate. PMID- 22296973 TI - Oestradiol valerate pretreatment in GnRH-antagonist cycles: a randomized controlled trial. AB - This randomized controlled trial analyses the ability to control the oocyte retrieval schedule of gonadotrophin-releasing hormone antagonist cycles through the administration of oestradiol valerate during the luteo-follicular transition period prior to the initiation of ovarian stimulation. Eighty-six women undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection were enrolled in the study. The control group (n = 42) received a standard ovarian stimulation protocol. In the pretreatment group (n = 44), patients were administered oestradiol valerate at a daily dose of 2 . 2 mg from day 25 of the preceding cycle onwards, during 6-10 consecutive days, depending on the day of the week. The primary endpoint was the proportion of patients undergoing oocyte retrieval during a weekend day (i.e. Saturday or Sunday), which was significantly lower in the pretreatment group (1/37, 2.7%) compared with the control group (8/39, 20.5%; P value = 0.029). The clinical pregnancy rates per started cycle were similar in the pretreatment group (38.6%) compared with the control group (38.1%). Pretreatment with oestradiol valerate results in a significantly lower proportion of patients undergoing oocyte retrieval during a weekend day and can be a valuable tool for the organization of an assisted reproduction centre. PMID- 22296974 TI - China's model of egg donation is a policy lesson for Britain. AB - In a move designed to increase the UK's supply of donor eggs, the Human Fertilisation and Embryology Authority has recently agreed to a fixed-sum compensation policy for donors "which better reflects their expenses" and inconvenience. Such a policy, however, which is reliant on non-patient donors for its success, is in contrast to what appears the system in China, where egg donors can only be recruited from those having IVF (i.e. patient donors) and on a conditional egg-sharing basis. Commitment to an egg-sharing policy in the UK would provide a more equitable system of egg donation than a compensation policy. PMID- 22296975 TI - Decreased free sphingoid base concentration in the plasma of patients with chronic systolic heart failure. AB - PURPOSE: In recent years, the role of sphingolipids in pathophysiology of the heart attracted much attention. Ceramide was found to be involved in the pathogenesis of cardiac dysfunction in animal models of ischemia/reperfusion injury, type 2 diabetes and lipotoxic cardiomyopathy. On the other hand, sphingosine-1-phosphate (S1P), has been shown to possess potent cardioprotective properties. The aim of the present study was to examine plasma concentrations of major sphingolipids in patients with chronic heart failure (HF). MATERIAL AND METHODS: The subjects were divided into two major groups: 1) with chronic systolic HF (n=47), and 2) healthy age-matched controls (n=15). Patients in the former group were further divided according to the underlying cause of HF (ischemic heart disease or idiopathic dilated cardiomyopathy, n=29 and 18, respectively). RESULTS: Plasma concentrations of S1P, sphinganine-1-phosphate and ceramide observed in both groups of HF patients were very close to these noted in the healthy controls, and no statistically significant differences were found. However, the level of free sphingosine and sphinganine in the plasma of patients with HF decreased by 25 and 27%, respectively, as compared to the control subjects. This effect was independent from the underlying cause of HF as the mean concentrations of these sphingoid bases in patients with ischemic and idiopathic HF were virtually the same. CONCLUSIONS: We conclude that chronic heart failure is associated with decreased concentration of free sphingoid bases in the plasma. However, despite lower availability of substrates required for synthesis of cardioprotective sphingoid base-1 phosphates, their plasma level remains stable. PMID- 22296976 TI - QRS detection based on wavelet coefficients. AB - Electrocardiogram (ECG) signal processing and analysis provide crucial information about functional status of the heart. The QRS complex represents the most important component within the ECG signal. Its detection is the first step of all kinds of automatic feature extraction. QRS detector must be able to detect a large number of different QRS morphologies. This paper examines the use of wavelet detail coefficients for the accurate detection of different QRS morphologies in ECG. Our method is based on the power spectrum of QRS complexes in different energy levels since it differs from normal beats to abnormal ones. This property is used to discriminate between true beats (normal and abnormal) and false beats. Significant performance enhancement is observed when the proposed approach is tested with the MIT-BIH arrhythmia database (MITDB). The obtained results show a sensitivity of 99.64% and a positive predictivity of 99.82%. PMID- 22296977 TI - Dietary patterns analysis using data mining method. An application to data from the CYKIDS study. AB - Data mining is a computational method that permits the extraction of patterns from large databases. We applied the data mining approach in data from 1140 children (9-13 years), in order to derive dietary habits related to children's obesity status. Rules emerged via data mining approach revealed the detrimental influence of the increased consumption of soft dinks, delicatessen meat, sweets, fried and junk food. For example, frequent (3-5 times/week) consumption of all these foods increases the risk for being obese by 75%, whereas in children who have a similar dietary pattern, but eat >2 times/week fish and seafood the risk for obesity is reduced by 33%. In conclusion patterns revealed from data mining technique refer to specific groups of children and demonstrate the effect on the risk associated with obesity status when a single dietary habit might be modified. Thus, a more individualized approach when translating public health messages could be achieved. PMID- 22296978 TI - Characterization and study of piperazinium salts, degradation products of nitrogen mustards by nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. AB - We synthesized and analyzed the degradation products, piperazinium salts from bis(2-chloroethyl)methylamine (HN2) and bis(2-chloroethyl)ethylamine (HN1) using 1H nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry (LC-MS). Piperazinium salt is the major degradation product of HN2, not N methyldiethanolamine above a concentration of 0.01 M in water and is a non scheduled chemical that may be generally assumed relevant to the Chemical Weapons Convention (CWC) within the context of the Organization for the Prohibition of Chemical Weapons (OPCW) proficiency test. In verification analysis, 1H NMR offers real-time information about degradation pathway of nitrogen mustards and LC-MS is expected to play an increasing role in the analysis of environmental samples for the degradation products of chemical warfare agents. PMID- 22296979 TI - An assessment of the accuracy and availability of data in electronic patient tracking systems for patients receiving HIV treatment in central Mozambique. AB - BACKGROUND: Since the rapid scale-up of antiretroviral therapy (ART) programs in sub-Saharan Africa, electronic patient tracking systems (EPTS) have been deployed to respond to the growing demand for program monitoring, evaluation and reporting to governments and donors. These routinely collected data are often used in epidemiologic and operations research studies intended to improve programs. To ensure accurate reporting and good quality for research, the reliability and completeness of data systems need to be assessed and reported. We assessed the completeness and reliability of EPTS used in 16 HIV care and treatment clinics in Manica and Sofala provinces of Mozambique. METHODS: We conducted a cross sectional study to assess the completeness and reliability of key variables in the electronic data system for patients enrolling in 16 public sector HIV treatment clinics between 1 July 2004 and 30 June 2008. Data from the electronic database was compared with data abstracted from a stratified random sample of 520 patient charts. Percent agreement, kappa scores and concordance correlation coefficients were calculated for specified variables. Percentile bootstrap confidence intervals were calculated to account for the stratified nature of our sampling. RESULTS: A total of 16,149 patients with a median age of 33 years and a median CD4 count of 151 enrolled in these 16 clinics between 1 July 2004 and 30 June 2008. The level of completeness was high for most variables with height (18.6%) and weight (11.5%) having the highest amount of missing data. The level of agreement for available data was also high with reliability statistics of 0.95 (95% CI: 0.92-0.98) for gender, 0.91 (95% CI: 0.80-1.00) for pre-ART CD4 value and 0.97 (95% CI: 0.95-0.99) for patient retention. CONCLUSIONS: Electronic patient tracking systems have been deployed to respond to the growing monitoring, evaluation and reporting requirements. In our cross-sectional study of clinics in Manica and Sofala provinces of Mozambique, we found high levels of completeness and reliability for key variables indicating that these electronic databases provided adequate data not only for monitoring and evaluation but also for research. Routine evaluations of the completeness and reliability of these databases need to occur to ensure high quality data are being used for reporting and research. PMID- 22296980 TI - Surgical excision of cardiac myxomas: twenty years experience at a single institution. AB - BACKGROUND: Primary cardiac tumors are quite uncommon and myxomas constitute the major proportion among these masses. The present study summarizes our 20-year clinical experience with surgical resection of intracardiac myxomas. METHODS: Between January 1990 and December 2007, 98 patients (42 males, mean age 60.4+/ 4.1 years) underwent complete excision of primary intracardiac myxoma. In 84 patients the origin site of the tumor was located in the left atrium, and the most common implant site was the interatrial septum. The most common symptom at admission was dyspnea, while systemic embolization was observed in 37 patients. Preoperative diagnosis was established in all patients by transthoracic echocardiography. All patients were operated through median sternotomy. RESULTS: Ninety-five patients (97%) survived the operation. Mean tumor dimension was 2.7+/ 1.3 cm in largest diameter. According to the St. John Sutton classification (St. John Sutton MG, Mercier LA, Giuliani ER, et al. Atrial myxomas: a review of clinical experience in 40 patients. Mayo Clin Pro 1980;55:371-6), solid tumors were detected in 43 patients (44%), while a papillary myxoma was found in 55 patients (56%). The follow-up was 100% complete, and the mean time to last follow up was 98+/-60 months. Of the 95 survivors, 3 patients (3%) died at a mean follow up of 72+/-45 months after surgery. Actuarial survival was 98%, 98%, and 89% at 5, 10, and 15 years, respectively. One patient operated for left atrial myxoma resection showed a recurrence 68 months after the first surgery. CONCLUSIONS: Although cardiac myxomas carry the risk of severe systemic and cardiac symptoms, prompt surgical excision gives excellent early and long-term results. PMID- 22296981 TI - Changes in left ventricular function after mitral valve repair for severe organic mitral regurgitation. AB - BACKGROUND: Limited data are available on the changes in left ventricular (LV) contractile function at long-term follow-up after mitral valve repair (MVr). Moreover, assessment of LV systolic function in patients undergoing MVr is troublesome with current methods, given that mitral regurgitation is characterized by increased preload and decreased afterload, potentially masking LV dysfunction. The aim of this study was to assess the value of LV global strain (longitudinal and circumferential) measured by speckle tracking analysis for detecting changes in contractile function after MVr. METHODS: A total of 122 patients with organic mitral regurgitation who underwent successful MVr at an early stage (LV ejection fraction>60%, LV end-systolic diameter<40 mm) were included. Echocardiography was performed at baseline and at short-term (~7 days) and long-term (1 to 3 years) follow-up after MVr. RESULTS: At baseline, LV ejection fraction and LV global strain were higher in patients than in 40 normal control individuals. By contrast, LV forward stroke volume was higher in control individuals than in patients. At short-term follow-up, a significant decrease in LV ejection fraction and LV global strain was noted as a consequence of changes in loading conditions. At long-term follow-up, LV ejection fraction and LV global strain improved significantly. Correction of LV strain for LV size showed a subtle impairment of myocardial contractility at baseline, which significantly improved over time after MVr, together with the improvement in LV forward stroke volume. CONCLUSIONS: Mitral valve repair for organic mitral regurgitation results in a significant increase in LV myocardial contractility as measured by LV global strain corrected by LV size. PMID- 22296982 TI - Radiofrequency ablation for stage I non-small cell lung cancer: management of locoregional recurrence. AB - BACKGROUND: This study characterizes the management of locoregional recurrence (LRR) in patients with high-risk stage I non-small cell lung cancer (NSCLC) treated with lung radiofrequency ablation (RFA). METHODS: Consecutive patients with biopsy-proven stage I NSCLC underwent computed tomography-guided lung RFA from December 2003 to 2010. All patients were deemed medically inoperable or refused an operation. RFA was performed with curative intent. RESULTS: Fifty-five ablations were performed in 45 patients (age, 51 to 89 years) with stage I NSCLC. At a median follow-up of 32 months, LRR occurred in 21 (38%) within a mean of 12+/-10 (range, 1-44) months from RFA. Recurrence was observed locally in the tumor bed in 18 (33%), in regional nodes in 4 (7%), and distant in 2 (4%). The mean maximal tumor diameter was 2.3+/-1.3 (range, 0.7 to 4.5) cm. In tumors exceeding 3 cm, 10 (80%) were associated with LRR. Recurrent lesions were treated with repeat RFA (5), radiotherapy (8), chemoradiotherapy (5), and chemotherapy (2). Local control was achieved by repeat RFA in 2 of 5 (40%) or by radiotherapy in 8 lesions (100%), with 2 regional nodal failures (median follow-up, 40+/-13 months). Overall survival among patients who did or did not experience LRR was similar (32% to 35%). Repeat RFA was not associated with any significant complications or procedure-related 30-day mortality. CONCLUSIONS: Lung RFA is associated with increased rates of local failure in tumors exceeding 3 cm and in contact with larger segmental vessels. Patients with local failure can be promptly salvaged with SBRT or repeat RFA, without detriment to overall survival. PMID- 22296983 TI - Stent design lowers angiographic but not clinical adverse events in stenting of symptomatic intracranial stenosis - results of a single center study with 100 consecutive patients. AB - BACKGROUND AND AIMS: Comparing safety and technical success of balloon-expandable stents and self-expanding stents for intracranial angioplasty and stenting in medically refractory intracranial atherosclerotic disease in a single center series. METHODS: Fifty-four self-expanding stents and 46 balloon-expandable stents were implanted in 100 consecutive patients (mean age 64 years, 74% male) from April 2000 to September 2009. All patients had symptomatic intracranial stenosis (anterior circulation, n = 40; posterior circulation, n = 60), presenting with recurrent transient ischemic attack or stroke under antithrombotic treatment. Mean degree of stenosis before treatment was 83 +/- 13%. We assessed safety, defined as any stroke or death during the procedure and at 30 days follow-up, and technical success, defined as accurate delivery of the stent at the site of the target lesion. RESULTS: Safety - periprocedural stroke or hemorrhage occurred in 11 patients treated with balloon-expandable stent, and in 14 of the patients treated with a self-expanding stent. One patient with a balloon-expandable stent died because of acute vessel rupture during treatment. One balloon-expandable stent and one self-expanding stent patient developed a severe reperfusion hemorrhage that resulted in death. Overall, the combined stroke and death rate at 30-day follow-up was 25.0% (23.9% for balloon-expandable stent group and 25.9% for the self-expanding stent group, P = 0.84). Technical success - intracranial angioplasty and stenting was technically successful in 96.3% of the self-expanding stent and 89.1% of the balloon-expandable stent patients (P = 0.31). Vascular complications were significantly less frequent in patients treated with a self-expanding stent (11.1%) than with a balloon expandable stent (36.9%, P = 0.002). CONCLUSION: Despite a high technical success, the rate of clinical adverse events at 30 days after intracranial angioplasty and stenting is high independently of the stent design. Thus, further development of intracranial stent systems and careful patient selection are mandatory. PMID- 22296984 TI - A latent variable approach to executive control in healthy ageing. AB - It is a well-established finding that the central executive is fractionated in at least three separable component processes: Updating, Shifting, and Inhibition of information (Miyake et al., 2000). However, the fractionation of the central executive among the elderly has been less well explored, and Miyake's et al. latent structure has not yet been integrated with other models that propose additional components, such as access to long-term information. Here we administered a battery of classic and newer neuropsychological tests of executive functions to 122 healthy individuals aged between 48 and 91 years. The test scores were subjected to a latent variable analysis (LISREL), and yielded four factors. The factor structure obtained was broadly consistent with Miyake et al.'s three-factor model. However, an additional factor, which was labeled 'efficiency of access to long-term memory', and a mediator factor ('speed of processing') were apparent in our structural equation analysis. Furthermore, the best model that described executive functioning in our sample of healthy elderly adults included a two-factor solution, thus indicating a possible mechanism of dedifferentiation, which involves larger correlations and interdependence of latent variables as a consequence of cognitive ageing. These results are discussed in the light of current models of prefrontal cortex functioning. PMID- 22296985 TI - Ignorance is no excuse: moral judgments are influenced by a genetic variation on the oxytocin receptor gene. AB - Perspective-taking has become a main focus of studies on moral judgments. Recent fMRI studies have demonstrated that individual differences in brain activation predict moral decision making. In particular, pharmacological studies highlighted the crucial role for the neuropeptide oxytocin in social behavior and emotional perception. In the present study N=154 participants were genotyped for a functional polymorphism (rs2268498) in the promoter region of the OXTR gene. We found a significant difference between carriers and non-carriers of the C-allele in exculpating agents for accidental harms (F((1,152))=11.49, p=.001, eta(2)=.07) indicating that carriers of the C-allele rated accidentally committed harm as significantly more blameworthy than non-carriers. This is the first study providing evidence for a genetic contribution to moral judgments. PMID- 22296986 TI - Cannabinoid modulation of noradrenergic circuits: implications for psychiatric disorders. AB - The interaction between the endocannabinoid system and catecholaminergic circuits has gained increasing attention as it is recognized that the development of synthetic cannabinoid receptor agonists/antagonists or compounds targeting endocannabinoid synthesis/metabolism may hold some therapeutic potential for the treatment of psychiatric disorders. The noradrenergic system plays a critical role in the modulation of emotional state, primarily related to anxiety, arousal, and stress. Recent evidence suggests that the endocannabinoid system mediates stress responses and emotional homeostasis, in part, by targeting noradrenergic circuits. This review summarizes our current knowledge regarding the anatomical substrates underlying regulation of noradrenergic circuitry by the endocannabinoid system. It then presents biochemical evidence showing an important effect of cannabinoid modulation on adrenergic receptor signaling. Finally, new evidence from behavioral pharmacology studies is provided demonstrating that norepinephrine is a critical determinant of cannabinoid induced aversion, adding another dimension to how central noradrenergic circuitry is regulated by the cannabinoid system. PMID- 22296987 TI - General surgery residency and international medical graduates: a perspective from Greece. PMID- 22296988 TI - The exposome: from concept to utility. PMID- 22296991 TI - Body mass index and mortality in China: a 15-year prospective study of 220 000 men. AB - BACKGROUND: In China, there have been few large prospective studies of the associations of body mass index (BMI) with overall and cause-specific mortality that have simultaneously controlled for biases that can be caused by pre-existing disease and smoking. METHODS: Prospective cohort study of 224 064 men, of whom 40 700 died during follow-up between 1990-91 and 2006. Analyses restricted to 142 214 men aged 40-79 years at baseline with no disease history and, to further reduce bias from pre-existing disease, at least 5 years of subsequent follow-up, leaving 17 800 deaths [including 4165 stroke, 1297 coronary heart disease (CHD), 3121 chronic obstructive pulmonary disease (COPD)]. Adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) per 5 kg/m(2) calculated within either a lower (15 to <23.5 kg/m(2)) or higher (23.5 to <35 kg/m(2)) range. RESULTS: The association between BMI and all-cause mortality was U-shaped with the lowest mortality at ~22.5-25 kg/m(2). In the lower range, 5 kg/m(2) higher BMI was associated with 14% lower mortality (HR 0.86, 95% CI 0.82-0.91); in the upper range, it was associated with 27% higher mortality (HR 1.27, 95% CI 1.15-1.40). The absolute excess mortality in the lower range was largely accounted for by excess mortality from specific smoking-related diseases: 54% by that for COPD, 12% other respiratory disease, 13% lung cancer, 11% stomach cancer. The excess mortality in the upper BMI range was largely accounted for by excess mortality from specific vascular diseases: 55% by that for stroke, 16% CHD. In this range, 5 kg/m(2) higher BMI was associated with ~50% higher mortality from stroke (HR 1.61, 95% CI 1.36-1.92) and CHD (HR 1.48, 95% CI 1.12-1.95). CONCLUSIONS: For China, previous evidence may have overestimated the excess mortality at low BMI but underestimated that at high BMI. The main way obesity kills in China appears to be stroke. PMID- 22296992 TI - Case report: successful lipid resuscitation in multi-drug overdose with predominant tricyclic antidepressant toxidrome. AB - We report a case of profound neurologic and cardiovascular manifestations of tricyclic antidepressant intoxication following self-poisoning with multiple pharmaceuticals including amitriptyline in excess of 43 mg/kg, in a 51-year-old male. Institution of mechanical ventilation, volume expansion, systemic alkalinisation (pH 7.51), and intermittent bolus metaraminol resulted in QRS narrowing but failed to resolve the developed shock. One 100-ml bolus of 20% lipid emulsion followed by a further 400 ml over 30 min was administered with restoration of haemodynamic stability, thereby curtailing the need for ongoing vasopressor medications. Assayed blood levels were consistent with the 'lipid sink' being a major effecter in the observed improvement. PMID- 22296993 TI - Iodobenzene diacetate (IBD) catalyzed an quick oxidative aromatization of Hantzsch-1,4-dihydropyridines to pyridines under ultrasonic irradiation. AB - This project was undertaken to demonstrate the potential of iodobenzene diacetate for the oxidative aromatization of Hantzch-1,4-dihydropyridines under ultrasonic irradiation. All reactions were carried out under ultrasonic irradiation and results were compared with traditional method. Sonochemical switching was observed in case of oxidative aromatization of 4-n-alkyl substituted 1,4-DHP. Without sonication, dealkylation occurred in case of n-alkyl substituted 1,4-DHP (ionic mechanism) but under ultrasonic irradiation, n-alkyl group was not expelled (radical mechanism). However, secondary alkyl (isopropyl) and benzyl group were expelled under both conditions. PMID- 22296994 TI - The effect of Clostridium perfringens type C strain CN3685 and its isogenic beta toxin null mutant in goats. AB - Clostridium perfringens type C is an important cause of enteritis and/or enterocolitis in several animal species, including pigs, sheep, goats, horses and humans. The disease is a classic enterotoxemia and the enteric lesions and associated systemic effects are thought to be caused primarily by beta toxin (CPB), one of two typing toxins produced by C. perfringens type C. This has been demonstrated recently by fulfilling molecular Koch's postulates in rabbits and mice. We present here an experimental study to fulfill these postulates in goats, a natural host of C. perfringens type C disease. Nine healthy male or female Anglo Nubian goat kids were inoculated with the virulent C. perfringens type C wild-type strain CN3685, an isogenic CPB null mutant or a strain where the cpb null mutation had been reversed. Three goats inoculated with the wild-type strain presented abdominal pain, hemorrhagic diarrhea, necrotizing enterocolitis, pulmonary edema, hydropericardium and death within 24h of inoculation. Two goats inoculated with the CPB null mutant and two goats inoculated with sterile culture media (negative controls) remained clinically healthy during 24h after inoculation and no gross or histological abnormalities were observed in the tissues of any of them. Reversal of the null mutation to partially restore CPB production also increased virulence; 2 goats inoculated with this reversed mutant presented clinical and pathological changes similar to those observed in goats inoculated with the wild-type strain, except that spontaneous death was not observed. These results indicate that CPB is required for C. perfringens type C to induce disease in goats, supporting a key role for this toxin in natural C. perfringens type C disease pathogenesis. PMID- 22296995 TI - More than classical Chlamydia psittaci in urban pigeons. AB - In the literature, studies of Chlamydia infection in birds have usually been confined to the search for Chlamydia (C., formerly Chlamydophila) psittaci, so that little is known about the presence of other chlamydial agents. In the present study, cloacal swabs and faeces samples of urban pigeons have been examined by real-time PCR, DNA microarray assays and partial ompA sequencing. Whilst C. psittaci was the predominant chlamydial agent in this pigeon population (75.8% of all Chlamydiaceae positives), the combined use of highly specific and sensitive molecular assays facilitated the detection of atypical serovars of C. psittaci, as well as other species of Chlamydia, such as C. abortus. Detection of C. pecorum and C. trachomatis from an avian host is reported here for the first time. Rather unexpectedly, 19.5% of all Chlamydiaceae-positive cases turned out to be infected with non-classified organisms. The considerable prevalence of these novel agents raises the question of their epidemiological importance and possible role as pathogens. Future surveys in domestic and wild birds will have to take the extended variety of chlamydial organisms into account. PMID- 22296996 TI - Does post-mastectomy radiotherapy represent a contraindication to skin-sparing mastectomy and immediate reconstruction: an update. AB - The use of skin-sparing mastectomy (SSM) to facilitate breast reconstruction is increasing due to a wide acceptance of improved cosmetic outcomes and evidence of equivalence in oncologic outcomes. The rates of patients undergoing mastectomy for whom post-mastectomy radiotherapy (PMRT) will be recommended is increasing as evidence of decreased loco-regional recurrence and increased survival mounts. PMRT may adversely effect complication rates and cosmetic outcomes for patients undergoing immediate breast reconstruction and PMRT--although the evidence for this is methodologically flawed. This article summarises the above evidence and highlights a reconstructive algorithm that may be used to mitigate the possible deleterious effects of PMRT on results. PMID- 22296997 TI - Effects of hepatocyte growth factor injection and reinjection on healing in the rabbit vocal fold. AB - OBJECTIVES/HYPOTHESIS: Hepatocyte growth factor (HGF) is a multifunctional polypeptide that plays various roles in embryogenesis and tissue regeneration and exhibits marked antifibrotic activity. The present study sought to assess the effects of HGF injection and reinjection coinciding with its peak of activity on collagen density, vessel density, inflammatory reaction in the lamina propria, and mean epithelial thickness in the injured rabbit vocal fold. STUDY DESIGN: Prospective, controlled, experimental animal study. METHODS: Fourteen rabbits were subdivided into two groups and underwent injury of the vocal folds. Immediately after injury, animals in group 1 received HGF injections into the right vocal fold (RVF), whereas those in group 2 received bilateral HGF injections and a single reinjection into the RVF 10 days after the first, to coincide with the peak of HGF activity. The left vocal folds (LVFs) served as controls in both groups. Histological assessment of laryngeal specimens was performed at 30 and 40 days, respectively. RESULTS: In both groups, collagen density was lower in the right (treated) vocal folds than in the left (control) folds (P=0.018). Vessel density was higher in the RVFs in group 2 (P=0.018). Differences were found in mean epithelial thickness and inflammatory reaction in the lamina propria but did not reach statistical significance. CONCLUSIONS: In the scarred rabbit vocal fold, HGF injection is associated with decreased collagen density in the lamina propria, whereas reinjection after 10 days produces decreased collagen density and higher vessel density. PMID- 22296998 TI - Animal model for training and improvement of the surgical skills in endolaryngeal microsurgery. AB - Animal models for training of surgical skills were widely used for a long time in the education of medical practitioners. It is recognized, however, that endolaryngeal microsurgery requires highly refined skills to handle the delicate structures of the vocal folds under the microscope. The availability of fresh human laryngeal specimens is markedly restricted by legal and hygienic issues. The aim of this work was to report on the design of a feasible and effective model to provide the much needed skills in an animal laryngeal model that is as close as possible to the human vocal fold structure. In the initial phase of the research, three animal larynges were studied: porcine/pig, bovine/calf, and ovine/sheep larynges. The pig/porcine larynx was chosen for this experimental training model because it closely resembled the human laryngeal/glottal configurations. A study was carried out on 10 porcine/pig larynges to assess the dimensions of the glottis and study the histology of the layered structure of the vocal fold. The study was pursued to confirm the resemblance of this animal specimen to the human vocal fold. A wooden box with a black finished interior was prepared with an acrylic bed at its floor. This bed allows placement of the porcine/pig larynx. The design of the box allows the endoscopic exposure of the porcine/pig larynx through a rubber diaphragm. The darkness and confinement of the box, apart from the light of the endoscope, approximates the situation in live endoscopy. The operating microscope is then used to expose the glottis. Routine fine microlaryngeal instruments were used for training in the prescribed skills. PMID- 22296999 TI - Repeated post-exercise administration with a mixture of leucine and glucose alters the plasma amino acid profile in Standardbred trotters. AB - BACKGROUND: The branched chain amino acid leucine is a potent stimulator of insulin secretion. Used in combination with glucose it can increase the insulin response and the post exercise re-synthesis of glycogen in man. Decreased plasma amino acid concentrations have been reported after intravenous or per oral administration of leucine in man as well as after a single per oral dose in horses. In man, a negative correlation between the insulin response and the concentrations of isoleucine, valine and methionine have been shown but results from horses are lacking. This study aims to determine the effect of repeated per oral administration with a mixture of glucose and leucine on the free amino acid profile and the insulin response in horses after glycogen-depleting exercise. METHODS: In a crossover design, after a glycogen depleting exercise, twelve Standardbred trotters received either repeated oral boluses of glucose, 1 g/kg body weight (BW) at 0, 2 and 4 h with addition of leucine 0.1 g/kg BW at 0 and 4 h (GLU+LEU), or repeated boluses of water at 0, 2 and 4 h (CON). Blood samples for analysis of glucose, insulin and amino acid concentrations were collected prior to exercise and over a 6 h post-exercise period. A mixed model approach was used for the statistical analyses. RESULTS: Plasma leucine, isoleucine, valine, tyrosine and phenylalanine concentrations increased after exercise. Post-exercise serum glucose and plasma insulin response were significantly higher in the GLU+LEU treatment compared to the CON treatment. Plasma leucine concentrations increased after supplementation. During the post-exercise period isoleucine, valine and methionine concentrations decreased in both treatments but were significantly lower in the GLU+LEU treatment. There was no correlation between the insulin response and the response in plasma leucine, isoleucine, valine and methionine. CONCLUSIONS: Repeated post-exercise administration with a mixture of leucine and glucose caused a marked insulin response and altered the plasma amino acid profile in horses in a similar manner as described in man. However, the decreases seen in plasma amino acids in horses seem to be related more to an effect of leucine and not to the insulin response as seen in man. PMID- 22297001 TI - Partnership and empowerment program: a model for patient-centered, comprehensive, and cost-effective care. AB - The Partnership and Empowerment Program model offers a comprehensive, patient centered, and cost-effective template for coordinating care for underinsured and uninsured patients with cancer. Attention to effective coordination, including use of internal and external resources, may result in decreased costs of care and improved patient compliance and health outcomes. PMID- 22297002 TI - Using an evidence-based practice process to change child visitation guidelines. AB - The multidimensional scope of nursing practice requires a nurse to provide not only physical and psychosocial interventions for patients, but also to support the family, particularly as the end of life approaches. One of the highest priorities for patients at the end of life is being able to spend time with the family members who are most important to them. In the case of a parent with young children, such visits can provide a sense of joy and peace that is important to the overall well-being of all. PMID- 22297003 TI - Clinical trials and communicating safely. AB - In the arena of clinical trials, patient safety is of the highest concern. Despite rules and regulations to protect participants, errors still occur. Deviations from standard practice, complexity, and unfamiliarity all may contribute to errors that occur in the research setting. Detailed and precise communication must exist between the research team and clinical staff to maintain patient safety and protocol integrity. PMID- 22297004 TI - Using nurse navigation to improve timeliness of lung cancer care at a veterans hospital. AB - The Connecticut Veterans Affairs Healthcare System (CT-VAHCS) sought to improve the timeliness of lung cancer care by filling the new position of cancer care coordinator with an advanced practice nurse (APN) functioning as a nurse navigator. The multifaceted nature of diagnosing lung cancer and the barriers encountered by patients and families as they access the complex healthcare system contributed to substantial delays in diagnosing and treating this disease. Beginning in January 2007 when the cancer care coordinator was hired, she recorded data regarding timeliness and stage at diagnosis for all patients diagnosed with non-small cell lung cancer. CT-VAHCS created and modified several processes to improve timeliness and quality of cancer care as soon as a patient's imaging suggested a new diagnosis of malignancy. The cancer care coordinator effected a measurable improvement in timeliness. In 2003, the average was 136 days from suspicion of cancer to treatment compared to 55 days in 2010, with a trend toward diagnosis of non-small cell lung cancer at an earlier stage. Oncology-certified APNs in the position of cancer care coordinator can engage multiple disciplines to generate process changes and improve timeliness of lung cancer care. PMID- 22297005 TI - Autoethnography: reflective journaling and meditation to cope with life threatening breast cancer. AB - Autoethnography is a qualitative research approach whereby the researcher shares personal stories that relate to the broader cultural context. Living through breast cancer showed me how reflective journaling and meditation can help one to cope with locally advanced breast cancer. The purpose of this autoethnography is to assist nurses in gaining a greater understanding of the primary cultural implications of (a) unresolved emotional issues from the past complicating current treatment and recovery for locally advanced breast cancer, and that (b) reflective journaling and meditation can provide an opportunity to "socially reconstruct" past psychological injury. In this example of autoethnography, I reconstructed the past by re-experiencing childhood wounds through meditation, accompanied by myself in the role of the nurturing mother providing comfort and support to the wounded inner child. That approach affirmed me in my current mothering role and provided imagery of the comfort that I was lacking in my childhood. Such duality empowered me toward self-acceptance and self-worth. Loss, grief, fear, and anxiety are considered universal states and emotions that interfere with quality of life. Finding meaning in suffering can heal pain and free energy for the pursuit of justice, peace, and joy. PMID- 22297006 TI - Biofield therapies and cancer pain. AB - The public and healthcare professionals have become increasingly aware and accepting of the benefit in physical, psychological, social, and spiritual support for patients with cancer. Patients with cancer often seek nonpharmacologic interventions to complement conventional care and decrease the pain associated with cancer and its treatment. Most often referred to as complementary and alternative medicine (CAM), these supportive therapies consist of a heterogeneous group of modalities used as adjuncts to allopathic health care. Biofield therapies are CAM modalities that involve the direction of healing energy through the hands to facilitate well-being by modifying the energy field of the body. This critical review of studies of biofield therapies emphasizes research using these modalities to decrease pain in patients with cancer. Although the therapies have demonstrated clinical efficacy, additional research is warranted. Oncology nurses should familiarize themselves with biofield therapies so they can offer informed recommendations to patients with cancer experiencing pain. PMID- 22297007 TI - Survey of experiences of an e-mentorship program: Part II. AB - Nurse educators (NEs) are responsible for providing continuing education to nurses, who are expected to remain knowledgeble in the diagnosis and management strategies of a range of cancers. Remaining abreast of up-to-date information can be a challenge. Part I of the e-mentorship program was developed in 2009 to provide NEs with the latest updates and educational materials to enhance multiple myeloma (MM) nursing knowledge. The second phase was completed in January 2011. Faculty developed four modules: overview of MM, peripheral neuropathy, bone health, and overview of transplantation. Seventeen MM nurses were identified to participate as mentors and partner with 34 mentees. Mentees were trained through monographs, journal articles, webcasts, and telephone communication, and then they presented the modules to their nurses. All mentees were asked to participate in voluntary pre- and post-test assessments to measure improved knowledge and clinical competence in the management of patients with MM. A significant improvement in post-test scores, as compared to pretest scores, was seen; therefore, nurses who participated in the e-mentorship program demonstrated improved knowledge. In the future, this type of educational program should be expanded to other cancer types. PMID- 22297008 TI - Update on the management of neuroendocrine tumors: focus on somatostatin antitumor effects. AB - Although neuroendocrine tumors (NETs) have been recognized as a family of complex malignancies since 1907, major progress has been made only in the past 20 years in understanding and managing the disease. The detection and reported incidence of NETs have increased fivefold since 1973, suggesting that the tumors may be more common than previously believed. NETs arise predominantly in the gastrointestinal tract but can occur in any tissue containing endocrine precursor cells and can secrete hormone peptides that exert clinical symptoms of flushing and diarrhea. With the introduction of the somatostatin analog (SSA) octreotide in 1987, symptom management of NETs improved by diminishing morbidities and mortality associated with carcinoid syndrome. Clinical results suggest that the SSA agents octreotide and lanreotide also may provide antitumor benefits in addition to their suppression of carcinoid syndrome. Oncology nurses should be aware of the expanded role of SSA agents for symptom management and tumor control in patients with NETs and communicate treatment benefits, side-effect management, and effective adherence with patients for the optimal clinical management of NETs. PMID- 22297009 TI - What men say about surviving prostate cancer: complexities represented in a decade of comments. AB - The experience of men who have completed cancer treatment and transitioned into survivorship is not well understood; therefore, a qualitative, descriptive, narrative analysis was conducted with open-ended questions that participants responded to annually during the course of a 10-year period. The participants expressed that the experience was complex and three themes were identified: "symptoms," "can't go back," and "needs." Time also emerged as an important concern. Participants indicated that sexual and physical symptoms impacted their entire life and that acknowledgment, information, and help from others were important to their recovery. Returning to baseline functioning was no longer possible; rather, a new normal now existed. The findings will help oncology nurses better understand the experience of being a prostate cancer survivor. The need for long-term interventions with information delivered prior to, during, and beyond the treatment process was identified. Clinical interventions should move toward a more integrated approach that helps men develop their new normal. PMID- 22297010 TI - Native cancer navigation: the state of the science. AB - The purpose of this literature review is to determine the current state of the science for the effectiveness of patient navigation on improving outcomes of cancer care across the continuum among Native Americans. The research will help healthcare professionals ascertain potential evidence-based practice guidelines and gaps in knowledge, which may provide direction for future research. Data synthesis included the use of Native navigation for cancer care, which has been demonstrated in limited, nonrandomized studies to improve cancer knowledge, access to care, and quality of life for Native Americans. Those studies had limitations, including small sample size, self-report of outcome measures, and lack of randomization. Evidence is insufficient to conclude that the use of Native navigation is superior to usual cancer care for Native American patients. Oncology nurses have a role in training personnel to serve as cancer navigators. Nurses need to be supportive of culturally appropriate navigation programs and know about services provided by navigators. In addition, nurse educators need to encourage Native Americans in their communities to consider choosing nursing as a profession. If an oncology nurse has an interest in research, opportunities exist to assist with or conduct research projects regarding Native cancer navigation. A particular need exists for addressing the gaps in research identified in this article. PMID- 22297011 TI - Interventional radiology in oncology: clinical management of patients undergoing transarterial chemoembolization for hepatic malignancies. AB - Interventional radiology procedures treat a variety of solid tumor malignancies. Transarterial chemoembolization (TACE) is a minimally invasive procedure performed under fluoroscopic guidance that is used in treatment of hepatic malignancies because of hepatocellular carcinoma or malignancy that has metastasized to the liver. Patients undergoing a TACE procedure may manifest postembolization symptoms such as fever, nausea, vomiting, and abdominal pain, which may persist after discharge. Patients need to be educated on the importance of compliance with prescribed medications, clinical symptoms to be expected, and signs of potential complications that need to be reported. PMID- 22297012 TI - Bortezomib-induced peripheral neuropathy in patients with multiple myeloma. AB - Bortezomib-induced peripheral neuropathy (BIPN) often is difficult to manage or reverse once it occurs. Treatment usually involves dose-reduction, interruption, or cessation of therapy, as no other interventions have been proven effective. Oncology nurses must be vigilant and recognize BIPN early to prevent patients from experiencing symptoms and complications that may interfere with their quality of life. PMID- 22297013 TI - Using care plans to enhance care throughout the cancer survivorship trajectory. AB - The Oncology Nursing Society (ONS) recognizes the importance of cancer survivorship and has launched several initiatives focused on cancer care since 2008. Cancer survivors are those who have been diagnosed with cancer, from the time of diagnosis until death. Recognizing the pivotal role that oncology nurses play in helping patients and their families navigate all phases of the cancer continuum, ONS has partnered with Journey Forward in the development of a survivorship care plan builder. PMID- 22297014 TI - Looking for hope and forgiveness. AB - Facing and owning up to my mistakes was something I learned as a child. In our house, if you told the truth and admitted what you had done wrong, there was no punishment. If you decided to run, hide, or lie, punishment was swift and non negotiable, with no hope of early release or pardon for subsequent good behavior. PMID- 22297016 TI - Strategic patient education program to prevent catheter-related bloodstream infection. AB - Central venous catheters (CVCs) are used commonly for venous access during treatment, and catheter-related bloodstream infection (CRBSI) is a frequent, yet highly preventable, hospital-acquired infection. One of the performance elements of the Joint Commission's 2012 National Patient Safety Goals addresses the education of patients and family members on CVC care and management, as well as CRBSI prevention before a central catheter is inserted. This article presents the history and roles of the Infusion Therapy Team at the University of Texas MD Anderson Cancer Center in CVC care and describes an organized patient education program that plays a key part in the institution's strategy to reduce and prevent CRBSI. Institutional standard policies and procedures for patient care should be in compliance with guidelines of the Centers for Disease Control and Prevention and the Joint Commission before any patient educational initiative is implemented. Such standards will serve as a guide to set up, organize, and implement an effective program. PMID- 22297017 TI - Developing an interprofessional care plan for an older adult woman with breast cancer: from multiple voices to a shared vision. AB - Interprofessional collaboration is central to quality patient care; however, little is known about developing interprofessional care plans, particularly in oncology. This article describes the development of an interprofessional care plan for an older adult woman with breast cancer. Two collaborative expert workshops were used; 15 clinical experts reviewed an online patient case and were asked to prepare a uniprofessional care plan. In workshop 1, participants worked from a draft interprofessional care plan, synthesized from the uniprofessional care plans by research associates, to arrive at consensus on an ideal interprofessional care plan. Using qualitative inductive content analysis of workshop transcripts, specific changes and overall key principles were identified and used to revise the draft plan. Based on these findings, a generalized interprofessional care plan/oncology model was developed. Revisions and proposed model were validated through consensus by participants during workshop 2. Participants highlighted the iterative, cyclical, and multilayered nature of patient care experiences; the importance of central patient profiles, which are contributed to and validated by all healthcare professionals; and the importance of assessing patient understanding. Participation of a patient representative provided an invaluable contribution. The process and model provide a unique framework for interprofessional care plan development in other settings and patient populations. PMID- 22297018 TI - A qualitative analysis of cancer-related fatigue in ambulatory oncology. AB - The purpose of this study was to describe patients' perceptions of the causes, relief, related symptoms, meaning, and suffering secondary to cancer-related fatigue (CRF). In total, 252 patients with breast, lung, colon, and prostate cancers were enrolled in a quasiexperimental study to test the effects of a clinical intervention on reducing barriers to symptom management in ambulatory care. Analysis of data reported in this article was derived from the Piper Fatigue Scale-Revised. Using qualitative research methods and content analysis, written statements related to the impact of CRF were coded using the following themes: patients' perceptions of CRF, causes, relief, related symptoms, meaning, and suffering. Comments were categorized and reviewed for content. Overall, CRF had a significant impact on physical, psychological, social, and spiritual well being. CRF limited the ability of participants to function, socialize, and participate in enjoyable activities. Emotional issues as a result of CRF were common. The negative impact of CRF on patients' overall well-being alters the meaning and suffering related to the cancer experience. The assessment of personal meaning and suffering related to CRF is an important component of the multidimensional assessment of CRF and will enable nurses to better understand the suffering related to CRF. PMID- 22297019 TI - The challenge of existential issues in acute care: nursing considerations for the patient with a new diagnosis of lung cancer. AB - A new diagnosis of lung cancer is a highly threatening experience that raises personally relevant existential issues and brings death-related thoughts and concerns to mind. Those issues can be very disturbing to patients, leading to distress and potentially to a lowered quality of life. The purpose of this article is to present to the practicing oncology nurse the types of existential and death-related concerns that patients with a new diagnosis of lung cancer may have. In addition, the article identifies practical strategies and resources for oncology nurses who can help patients accept and manage the normal but often distressing responses to a life-threatening diagnosis. PMID- 22297020 TI - Sciatic lateral popliteal block with clonidine alone or clonidine plus 0.2% ropivacaine: effect on the intra-and postoperative analgesia for lower extremity surgery in children: a randomized prospective controlled study. AB - BACKGROUND: The effect of adding clonidine to local anesthetics for nerve or plexus blocks remains unclear. Most of the studies in adults have demonstrated the positive effects of clonidine on intra- and postoperative analgesia when used as an adjunctive agent or in some cases as a single to regional techniques. In the pediatric population, there are only few trials involving clonidine as an adjunct to regional anesthesia, and the analgesic benefits are not definite in this group of patients. The evidence concerning perineural administration of clonidine is so far inconclusive in children, as different types and volume of local anesthetic agents have been used in these studies. Moreover, the efficacy of regional anesthesia is largely affected by the operator's technique, accuracy and severity of operation. METHODS: The use of clonidine alone or combined with 0.2% ropivacaine for effective analgesia after mild to moderate painful foot surgery was assessed in 66 children, after combined sciatic lateral popliteal block (SLPB) plus femoral block. The patients were randomly assigned into three groups to receive placebo, clonidine, and clonidine plus ropivacaine. Time to first analgesic request in the groups was analyzed by using Kaplan-Meier and the log-rank test (mean time, median time, 95% CI). RESULTS: In our study, clonidine administered alone in the SLPB seems promising, maintaining intraoperatively the hemodynamic parameters SAP, DAP, HR to the lower normal values so that no patient needed nalbuphine under 0.6 MAC sevoflurane anesthesia, and postoperatively without analgesic request for a median time of 6 hours. In addition, clonidine administered as adjuvant enhances ropivacaine's analgesic effect for the first postoperative day in the majority of children (p = 0.001). Clonidine and clonidine plus ropivacaine groups also didn't demonstrate PONV, motor blockade, and moreover, the parents of children expressed their satisfaction with the excellent perioperative management of their children, with satisfaction score 9.74 +/- 0.45 and 9.73 +/- 0.70 respectively. On the contrary all the patients in the control group required rescue nalbuphine in the recovery room, and postoperatively, along with high incidence of PONV, and the parents of children reported a low satisfaction score (7.50 +/- 0.70). CONCLUSIONS: Clonidine appears promising more as an adjuvant in 0.2% ropivacaine and less than alone in the SLPB plus femoral block in children undergoing mild to moderate painful foot surgery, with no side effects. TRIAL REGISTRATION: ClinicalTrials.gov, ISRCTN90832436, (ref: CCT-NAPN-20886). PMID- 22297021 TI - Photo-catalyzed degradation of hazardous dye methyl orange by use of a composite catalyst consisting of multi-walled carbon nanotubes and titanium dioxide. AB - The high rate of electron/hole pair recombination reduces the quantum yield of the processes with TiO(2) and represents its major drawback. Adding a co adsorbent increases the photocatalytic efficiency of TiO(2). In order to hybridize the photocatalytic activity of TiO(2) with the adsorptivity of carbon nanotube, a composite of multi-walled carbon nanotubes and titanium dioxide (MWCNT/TiO(2)) has been synthesized. The composite was characterized by means of X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), Fourier transform infrared absorption spectroscopy (FTIR), and diffuse reflectance UV-vis spectroscopy. The catalytic activity of this composite material was investigated by application of the composite for the degradation of methyl orange. It was observed that the composite exhibits enhanced photocatalytic activity compared with TiO(2). The enhancement in photocatalytic performance of the MWCNT/TiO(2) composite is explained in terms of recombination of photogenerated electron-hole pairs. In addition, MWCNT acts as a dispersing agent preventing TiO(2) from agglomerating activity during the catalytic process, providing a high catalytically active surface area. This work adds to the global discussion of how CNTs can enhance the efficiency of catalysts. PMID- 22297022 TI - A comparative kinetic study on ultra-deep hydrodesulfurization of pre-treated gas oil over nanosized MoS2, CoMo-sulfide, and commercial CoMo/Al2O3 catalysts. AB - Unsupported nanosized MoS(2) and CoMo-sulfide catalysts were synthesized, and their catalytic performances for the deep hydrodesulfurization (HDS) of treated gas oil were investigated as compared with that of a CoMo/Al(2)O(3) catalyst. The HDS reactions were carried out in a batch autoclave reactor at 340 degrees C and 3 MPa H(2). The CoMo-sulfide catalyst shows the highest activity and can reduce the sulfur content to less than 10 ppm. The decrease in total sulfur content as a function of reaction time was found to follow pseudo-second order kinetics (empirical form). The change in the concentration of some individual representative sulfur-containing species in gas oil as a function of time was found to follow pseudo-first-order kinetics. However, the change in combined concentration of these species in the gas oil during HDS with the reaction time was found to corroborate pseudo-second-order kinetics. A kinetic model approach was proposed from which an estimation of the intrinsic kinetic data can be achieved. The model fitted the obtained data reasonably well, suggesting its potential for better assessment of the catalytic activity in the HDS of real feedstock. The study reveals that ranking of catalyst activities using model refractory sulfur-containing compounds does not necessarily imply a typical rank in case of investigating the real feedstocks. PMID- 22297023 TI - Effect of hydrocarbon structure of the headgroup on the thermodynamic properties of micellization of cationic gemini surfactants: an electrical conductivity study. AB - A series of cationic gemini surfactants butanediyl-1,4-bis(dodecyldialkylammonium bromide), C(12)H(25)N(+)(C(m)H(2)(m)(+1))(2)C(4)H(8)N(+)(C(m)H(2)(m)(+1))(2)C(12)H(25).2Br( ), where m=1, 2, 3, 4, referred to as C(12)C(4)C(12)(Me), C(12)C(4)C(12)(Et), C(12)C(4)C(12)(Pr), and C(12)C(4)C(12)(Bu), respectively, were synthesized, and their thermodynamic properties of micellization were studied by electrical conductivity measurements. There existed a minimum critical micelle concentration (cmc) in the curve of cmc versus temperature, and the temperature of the minimum of cmc (T(min)) increased with increasing the headgroup alkyl chain length. The values of log (cmc) depended linearly on carbon number of the alkyl chains, but that was not true for the carbon number of the headgroup substituents. The temperature dependence of cmc and degree of counterion association (beta) were used to calculate the Gibbs free energy (Delta(mic)G degrees ), enthalpies (Delta(mic)H degrees ) and entropies (Delta(mic)S degrees ) of micelle formation for these gemini surfactants, and well correlated enthalpy-entropy compensation was observed. The analyses showed C(12)C(4)C(12)(Me) and C(12)C(4)C(12)(Et) behaved similarly in terms of thermodynamics of micellization, but they behaved differently from C(12)C(4)C(12)(Pr) and C(12)C(4)C(12)(Bu), which could be ascribed to the hydrophobicity and the location of the headgroup alkyl chains in the aggregates. These initial results indicate the headgroup alkyl chain plays an important role in influencing the thermodynamic properties of gemini surfactants. PMID- 22297024 TI - Strong coupling among semiconductor quantum dots induced by a metal nanoparticle. AB - Based on cavity quantum electrodynamics (QED), we investigate the light-matter interaction between surface plasmon polaritons (SPP) in a metal nanoparticle (MNP) and the excitons in semiconductor quantum dots (SQDs) in an SQD-MNP coupled system. We propose a quantum transformation method to strongly reveal the exciton energy shift and the modified decay rate of SQD as well as the coupling among SQDs. To obtain these parameters, a simple system composed of an SQD, an MNP, and a weak signal light is designed. Furthermore, we consider a model to demonstrate the coupling of two SQDs mediated by SPP field under two cases. It is shown that two SQDs can be entangled in the presence of MNP. A high concurrence can be achieved, which is the best evidence that the coupling among SQDs induced by SPP field in MNP. This scheme may have the potential applications in all-optical plasmon-enhanced nanoscale devices. PMID- 22297025 TI - Long term respiratory outcomes of congenital diaphragmatic hernia, esophageal atresia, and cardiovascular anomalies. AB - Intrathoracic congenital malformations may be associated with long-term pulmonary morbidity. This certainly is the case for congenital diaphragmatic hernia, esophageal atresia and cardiac and aortic arch abnormalities. These conditions have variable degrees of impaired development of both the airways and lung vasculature, with a postnatal impact on lung function and bronchial reactivity. Pulmonary complications are themselves frequently associated to non-pulmonary morbidities, including gastrointestinal and orthopaedic complications. These are best recognized in a structured multidisciplinary follow-up clinic so that they can be actively managed. PMID- 22297026 TI - CXCL12 as a biological marker for the diagnosis of tuberculous pleurisy. AB - Although a chemokine CXCL12 is implicated in some infectious diseases, especially those in which T cell-mediated immunity plays critical roles, the relevance of CXCL12 to tuberculosis has never been elucidated. To determine the clinical efficacy of CXCL12 as a diagnostic marker for tuberculous (TB) pleurisy, we measured CXCL12 concentration in pleural fluid and serum from patients with various etiologies. Of 60 patients with pleural fluid, the median age of TB patients was 52 which was significantly lower than 71 of non-TB patients (P < 0.01). CXCL12 level in TB effusion (4456 +/- 1013 pg/mL, n = 15) was significantly higher than non-TB effusion (2851 +/- 1229 pg/mL, n = 45) (P < 0.01). On the other hand, serum CXCL12 level showed no significant differences among TB pleurisy, non-TB pleurisy, and normal healthy subjects. The sensitivity and specificity of CXCL12 in pleural fluid for the diagnosis of TB pleurisy was 60.0% and 93.2% (cut-off value = 4600 pg/mL), respectively. Area under the receiver operating characteristic (ROC) curve (AUC) for CXCL12 was 0.84. As the source of CXCL12, pleural mesothelium, endothelium of pulmonary vessels, bronchial epithelium, multinucleated giant epithelioid cells, and macrophages were positive for CXCL12 staining. Increased CXCL12 level in pleural fluid could be an informative diagnostic marker for differentiating TB pleurisy from other etiologies. PMID- 22297027 TI - Enhanced depth imaging optical coherence tomography of choroidal nevus in 104 cases. AB - PURPOSE: To describe the characteristics of choroidal nevus using the enhanced depth imaging (EDI) feature of spectral-domain optical coherence tomography (OCT). DESIGN: Retrospective, observational case series. PARTICIPANTS: One hundred four eyes with choroidal nevus. METHODS: Spectral-domain EDI OCT was performed with a Heidelberg Spectralis HRA+OCT (Heidelberg Engineering, Heidelberg, Germany) using a custom scan acquisition protocol of up to 13 raster lines of 9-mm scan length with automatic real-time image averaging set at 100 images. The thickness of choroidal nevus was measured by combining Heidelberg's autosegmentation with manual segmentation. MAIN OUTCOME MEASURES: Imaging features and thickness correlation of choroidal nevus by EDI OCT versus standard ultrasonography. RESULTS: Of 104 eyes with choroidal nevus imaged with EDI OCT, 51 (49%) displayed image detail suitable for study. The remaining 53 cases were suboptimal because of statistically identified factors of age older than 60 years (P = 0.027), female gender (P = 0.008), extramacular location of nevus (P<0.001), mean distance from foveola more than 3 mm (P = 0.002), mean distance from optic disc more than 4 mm (P<0.001), and mean maximal basal diameter more than 5 mm (P = 0.006). Of the 51 suitable cases, mean nevus thickness was 685 MUm (median, 628 MUm; range, 184-1643 MUm) by EDI OCT compared with 1500 MUm (median, 1500 MUm; range, 1000-2700 MUm) by ultrasonography. The most common EDI OCT imaging features included partial (59%) or complete (35%) choroidal shadowing deep to the nevus, choriocapillaris thinning overlying the nevus (94%), retinal pigment epithelial (RPE) atrophy (43%), RPE loss (14%), RPE nodularity (8%), photoreceptor loss (43%), inner segment-outer segment junction (IS-OS) irregularity (37%), IS-OS loss (6%), external limiting membrane irregularity (18%), outer nuclear and outer plexiform layer irregularity (8%), and inner nuclear layer irregularity (6%). Overlying subretinal fluid was identified by EDI OCT (16%), ophthalmoscopic examination (8%), and ultrasonographic evaluation (0%). A comparison of pigmented versus nonpigmented nevus showed only 1 significant difference of more intense choroidal shadowing with pigmented nevus (P = 0.046). CONCLUSIONS: Imaging of choroidal nevus with EDI OCT enables precise measurement of tumor thickness with comparatively reduced thickness relative to ultrasonography. Using EDI OCT, 94% of choroidal nevi were found to have overlying choriocapillaris thinning. PMID- 22297028 TI - Detection of new-onset choroidal neovascularization using optical coherence tomography: the AMD DOC Study. AB - PURPOSE: To determine the sensitivity of time domain optical coherence tomography (OCT) in detecting conversion to neovascular age-related macular degeneration (AMD) in eyes at high risk for choroidal neovascularization (CNV), compared with detection using fluorescein angiography (FA) as the gold standard. DESIGN: Prospective, multicenter, observational study. PARTICIPANTS: Individuals aged >=50 years with nonneovascular AMD at high risk of progressing to CNV in the study eye and evidence of neovascular AMD in the fellow eye. METHODS: At study entry and every 3 months through 2 years, participants underwent best-corrected visual acuity, supervised Amsler grid testing, preferential hyperacuity perimetry (PHP) testing, stereoscopic digital fundus photographs with FA, and OCT imaging. A central Reading Center graded all images. MAIN OUTCOMES MEASURES: The sensitivity of OCT in detecting conversion to neovascular AMD by 2 years, using FA as the reference standard. Secondary outcomes included comparison of sensitivity, specificity, positive predictive value, and negative predictive value of OCT, PHP, and supervised Amsler grid relative to FA for detecting incident CNV. RESULTS: A total of 98 participants were enrolled; 87 (89%) of these individuals either completed the 24-month visit or exited the study after developing CNV. Fifteen (17%) study eyes had incident CNV confirmed on FA by the Reading Center. The sensitivity of each modality for detecting CNV was: OCT 0.40 (95% confidence interval [CI], 0.16-0.68), supervised Amsler grid 0.42 (95% CI, 0.15-0.72), and PHP 0.50 (95% CI, 0.23-0.77). Treatment for incident CNV was recommended by the study investigator in 13 study eyes. Sensitivity of the testing modalities for detection of CNV in these 13 eyes was 0.69 (95% CI, 0.39 0.91) for OCT, 0.50 (95% CI, 0.19-0.81) for supervised Amsler grid, and 0.70 (95% CI, 0.35-0.93) for PHP. Specificity of the OCT was higher than that of the Amsler grid and PHP. CONCLUSIONS: Time-domain OCT, supervised Amsler grid, and PHP have low to moderate sensitivity for detection of new-onset CNV compared with FA. Optical coherence tomography has greater specificity than Amsler grid or PHP. Among fellow eyes of individuals with unilateral CNV, FA remains the best method to detect new-onset CNV. PMID- 22297029 TI - Postcataract surgery endophthalmitis in the United States: analysis of the complete 2003 to 2004 Medicare database of cataract surgeries. AB - OBJECTIVE: To estimate endophthalmitis incidence after cataract surgery nationally and at the state level in 2003 and 2004 and to explore risk factors. DESIGN: Analysis of Medicare beneficiary claims data. PARTICIPANTS: We evaluated billed claims for cataract surgery and endophthalmitis diagnosis and treatment for all Medicare fee-for-service beneficiaries in 2003-2004. METHODS: Cataract surgeries were identified by procedure codes and merged with demographic information. Cataract annual surgical volume was calculated for all surgeons. Presumed postoperative endophthalmitis cases were identified by International Classification of Diseases-9 Clinical Modification Codes on claims within 42 days after surgery. Endophthalmitis rates and 95% confidence intervals (CI) were calculated at state and national levels. Logistic regression was used to investigate the association between developing endophthalmitis and surgery location and surgeon factors. MAIN OUTCOME MEASURES: Endophthalmitis incidence and risk factors. RESULTS: We included 4006 cases of presumed endophthalmitis, which occurred after 3 280 966 cataract surgeries. The national rate in 2003 was 1.33 per 1000 surgeries (95% CI, 1.27-1.38) and decreased to 1.11 per 1000 (95% CI, 1.06-1.16) in 2004. Males (relative risk [RR], 1.23; 95% CI, 1.15-1.31), older individuals (RR, 1.53; 95% CI, 1.38-1.69; >=85 compared with 65-74 years), blacks (RR, 1.17; 95% CI, 1.03-1.33), and Native Americans (RR, 1.72; 95% CI, 1.07-2.77) had increased risk of disease. After adjustment, surgeries by surgeons with low annual volume (RR, 3.80; 95% CI, 3.13-4.61 for 1-50 compared with >=1001 annual surgeries) and less experience (RR, 1.41; 95% CI, 1.25-1.59 for 1-10 compared with >=30 years), and surgeries performed in 2003 (RR, 1.20; 95% CI, 1.13-1.28) had increased endophthalmitis risk. CONCLUSIONS: Endophthalmitis rates are lower than previous yearly US estimates, but remain higher than rates reported from a series of studies from Sweden; patient factors or methodologic differences may contribute to differences across countries. Patient age, gender, and race, and surgeon volume and years of experience are important risk factors. PMID- 22297030 TI - Intraoperative ultrasonography-guided positioning of iodine 125 plaque brachytherapy in the treatment of choroidal melanoma. AB - PURPOSE: To report intraoperative ultrasonography-guided positioning of iodine 125 (I(125)) plaques for brachytherapy of choroidal melanoma as a quality improvement measure. DESIGN: Retrospective, single-center, consecutive case cohort study. PARTICIPANTS: One hundred fifty consecutive patients with choroidal melanoma. METHODS: Patients with choroidal melanoma who were treated with I(125) plaque brachytherapy from January 2007 through January 2011 with at least 6 months of clinical follow-up were included. MAIN OUTCOME MEASURES: Patient and tumor characteristics at diagnosis were tabulated. The need for plaque repositioning if intraoperative ultrasonography showed the plaque to be either not centered on the tumor or if there was less than 1.0 mm of plaque margin beyond the tumor border was recorded. The rate of local treatment failure and occurrence of distant metastasis were determined. RESULTS: The average interval from surgery to last follow-up was 21.5 months. Fifty-four (36%) of 150 patients required plaque repositioning. Of tumors located in the macula, equator, and periphery, 15 (36.6%), 26 (36.6%), and 13 (34.2%) required repositioning. There was no case of local treatment failure during a mean follow-up of 21.5 months (range, 6-48 months). Clinical evidence of choroidal melanoma metastasis developed in 9 patients. The cumulative 2-year Kaplan-Meier rate of local treatment failure in the cohort was statistically lower compared with the Collaborative Ocular Melanoma Study, which did not require ultrasonography-guided plaque positioning. CONCLUSIONS: Intraoperative ultrasonography identified the need to reposition I(125) plaques to achieve centration and plaque margin (>1.0 mm) beyond the tumor border in 36% of eyes. Neither tumor size nor tumor location correlated with the need to reposition the plaque. There was no case of local treatment failure during follow-up in this series. Correct plaque position is an essential component of quality outcomes in brachytherapy. Intraoperative ultrasonography reduces geographic errors in placement in eye plaque therapy and may help to reduce local treatment failure in choroidal melanoma. PMID- 22297031 TI - Comparative study of limbal stem cell deficiency diagnosis methods: detection of MUC5AC mRNA and goblet cells in corneal epithelium. AB - PURPOSE: To evaluate a limbal stem cell deficiency (LSCD) diagnosis method based on the detection of the MUC5AC transcript by reverse transcription-polymerase chain reaction (RT-PCR) in comparison with the standard diagnostic method based on goblet cell detection by periodic acid-Schiff (PAS)-hematoxylin staining, using samples obtained from corneal epithelium impression cytology (IC). DESIGN: Transversal, comparative case series. PARTICIPANTS: We studied 59 eyes from 43 patients clinically diagnosed with LSCD. METHODS: Impression cytology was used to gather cells from corneal and conjunctival epithelium from the same eye. The presence of goblet cells in the cornea was determined by PAS-hematoxylin staining, whereas the presence of the MUC5AC transcript was detected by RT-PCR using a custom-designed primer pair. MAIN OUTCOME MEASURES: Goblet cells in the corneal epithelium were detected by light microscopy, and the MUC5AC transcript was detected as the corresponding PCR amplicon in agarose gels. RESULTS: Our study included 59 corneal samples, together with their respective conjunctival samples for RT-PCR assays. Of these, 47 samples were also available for comparative PAS-hematoxylin staining. The MUC5AC amplicon was detected in 56 of 59 (94.9%) corneal epithelium samples. In contrast, conventional IC staining detected goblet cells in only 17 of 47 (36.2%) samples; these were not found in 27 of 47 (57.4%) samples (negative results), and 3 of 47 (6.4%) showed inconclusive results. CONCLUSIONS: The detection of the MUC5AC transcript in corneal epithelium is a more sensitive method to diagnose LSCD than the conventional PAS-hematoxylin method, although a minimum RNA concentration of 1.2 ng/MUl is required for negative results to be reliable. Moreover, RT-PCR is a highly specific and more objective technique. Overall, these findings indicate that molecular analysis facilitates a more precise clinical diagnosis of LSCD, thereby reducing the risk of surgical failure. PMID- 22297032 TI - Novel MSX1 mutation in a family with autosomal-dominant hypodontia of second premolars and third molars. AB - OBJECTIVE: Tooth agenesis is the most common developmental anomaly of the human dentition, with aetiology involving both genetic and environmental factors. The aim of the study was to search for casual mutations underlying hypodontia in a family with agenesis of the second premolars and third molars. DESIGN: Direct sequencing of the coding regions including exon-intron boundaries of the MSX1 and PAX9 genes was performed in all affected family members. RESULTS: Novel heterozygous mutation segregating in an autosomal dominant model was identified in the MSX1 gene. This c.T671C transition leads to a substitution of leucine by proline at position 224, which is the penultimate amino acid residue of the highly conserved homeodomain. None of the control subjects (600 chromosomes) were carriers of this novel, probably damaging to protein function, mutation. CONCLUSIONS: Our results demonstrate for the first time that MSX1 might play a substantial role in familial cases of hypodontia involving only second premolars and third molars. The novel c.T671C mutation might be the etiological variant of the MSX1 gene responsible for the lack of permanent teeth in the tested family. PMID- 22297033 TI - The early phase response of rat alveolar bone to traumatic occlusion. AB - OBJECTIVES: Occlusal trauma is an important factor to influence alveolar bone remodelling, the effect of which includes many cytokines and signalling pathways. However, the exact mechanism of the traumatic stimulus for alveolar remodelling is still unclear. The purpose of the present study was to investigate the early responses of alveolar osteocytes to occlusal trauma through genome-wide microarray. METHODS: The occlusal surface of the upper left first molar of rat was raised by placing a stainless steel wire to induce occlusal trauma in the lower left first molar. After 24 h, we took out the alveolar bone tissue of the first molars at the both sides of rats' lower jaws under anaesthesia. The different gene expressions were showed by genome-wide microarray, which comprises about 27,000 genes and the results were examined by quantitative RT-PCR. RESULT: Of the approximately 27,000 genes, the expression of 586 genes was strongly changed. These findings clearly demonstrated that in the early response of the alveolar bone to occlusal trauma, the expression of osteoblast, collagens, bone mineralization, bone remodelling and WNT, TGF-beta pathway related cytokines decreased, and osteoclast-specific cytokines have no significant changes in expression. CONCLUSION: These results suggested that at early phase of the occlusal trauma, osteogenesis in rat's alveolar bone was inhibited, and osteoclastogenesis was not significant. PMID- 22297034 TI - A reappraisal of stroke mortality trends in Brazil (1979-2009). AB - BACKGROUND: Brazil has one of the highest cerebrovascular death rates in the Western Hemisphere. We investigated temporal trends according to gender and stroke subtypes. METHODS: We analyzed mortality rates between 1979 and 2009 for different stroke subtypes. Data were stratified by gender and age (35-74 years). The annual percent change and significant changes in the trends were identified with Poisson regression. RESULTS: After excluding deaths due to sequel from stroke for men, the annual percent changes (95% confidence intervals) were as follows: 1979-1984, 0.7 (-0.8 to 2.1); 1984-1994, -1.8 (-2.4 to -1.2); 1994-2007, -5.0 (-5.4 to -4.7); and 2007-2009, -0.8 (-7.0 to 5.8). For women, the annual percent changes were as follows: 1979-1994, -1.9 (-2.2 to -1.6); 1994-1997, -7.5 (-14.0 to -0.6); 1997-2007, -4.0 (-4.6 to -3.3); and 2007-2009, 1.6 (-5.5 to 9.2). For the 2006-2009 period, the average annual percent change (95% confidence interval) for all strokes was -3.1 (-3.3 to -2.9) for men and -2.9 (-3.1 to -2.8) for women. For the same period, the average annual percent change of death rates for stroke subtypes were, for men and women, respectively: intracerebral hemorrhage, -4.0 (-4.9 to -3.1) and -2.9 (-3.4 to -2.3); and ischemic stroke, 3.2 (-3.3 to -3.0) and -1.4 (-2.0 to -0.9). CONCLUSION: Stroke mortality rates are declining in Brazil for all stroke subtypes. PMID- 22297035 TI - Vibrational spectroscopic studies and computational calculations of 5-chloro-2-(3 chlorophenylcarbamoyl)phenylacetate. AB - The FT-IR and FT-Raman spectra of 5-chloro-2-(3 chlorophenylcarbamoyl)phenylacetate were studied. The vibrational wave numbers and corresponding vibrational assignments were examined theoretically using the Gaussian 03 set of quantum chemistry codes and the normal modes are assigned by Potential Energy Distribution calculations. The synthesis, elemental analysis and NMR values are presented. The red shift of the NH stretching wave number in the infrared spectrum from the computed wave number indicates the weakening of the NH bond resulting in proton transfer to the neighboring oxygen atom. The first hyperpolarizability, infrared intensities and Raman activities are reported. The calculated first hyperpolarizability is comparable with the reported values of similar derivatives and is an attractive object for future studies of nonlinear optics. The geometrical parameters of the title compound are in agreement with that of similar reported derivatives. PMID- 22297036 TI - A facile hydrothermal approach for construction of carbon coating on TiO2 nanoparticles. AB - Herein a facile hydrothermal approach is used to construct carbon coated TiO2 nanoparticles employing dextrose as the source of carbon. The procedure is operated at a low temperature of 200 degrees C. Fourier infrared spectroscopy demonstrated the successful coating of carbon on TiO2 nanoparticles. The phase composition of TiO2 and carbon coated TiO2 nanoparticles were studied using X-ray diffraction and the surface morphology was analyzed by scanning and transmission electron microscopy. The existence of carbon coating on TiO2 nanoparticles was revealed by thermogravimetric analysis through different thermograms exhibited for TiO2 and carbon coated TiO2 nanoparticles. The reported method offers a simple and efficient approach for production of carbon coated TiO2 nanoparticles. PMID- 22297037 TI - GRACE risk score predicts contrast-induced nephropathy in patients with acute coronary syndrome and normal renal function. AB - We evaluated the incidence, clinical predictors, and outcomes of contrast-induced nephropathy (CIN) after coronary angiography in patients with myocardial infarction and normal kidney function. We studied 202 consecutive patients with glomerular filtration rate >60 mL/min/1.73 m(2). The CIN was defined according to 3 definitions: increases in serum creatinine (sCr) >=25%, >=0.3 mg/dL, and >=0.5 mg/dL. The CIN occurred in 56 (27.7%), 42 (20.8%), and 13 (6.4%) patients, respectively. In multivariate analysis, the presence of a high Global Registry of Acute Coronary Events (GRACE) risk score (>140) was an independent predictor of CIN in its milder forms (>=25% and >=0.3 mg/dL of rise in sCr). Increase in sCr >=0.3 mg/dL was an independent predictor of bleeding. Increase in sCr >=0.5 mg/dL was an independent predictor of in-hospital cardiac events (mortality, myocardial infraction [MI], and heart failure). As conclusion, the GRACE score is a useful tool to predict CIN in patients with MI and normal renal function. PMID- 22297038 TI - Internal medicine interns have a poor knowledge of peripheral artery disease. AB - Peripheral arterial disease (PAD) is common and carries an increased risk of morbidity and mortality. The level of knowledge among incoming medical trainees about PAD is unknown. During orientation to a single internal medicine residency program, incoming medical interns were given a 19-question multiple-choice questionnaire. The questions fell into 1 of 4 categories about PAD: (1) prevalence, (2) screening, (3) treatment, and (4) outcome. Sixty-two incoming interns were queried. The percentage of questions answered correctly overall was 41.7% (10.5%-73.7%). The percentage of questions answered correctly in the prevalence, screening, treatment, and outcome groups were 48.9% (0 to 100%), 33.8% (0 to 80%), 45.0% (0 to 87.5%), and 42.5% (0 to 100%), respectively. Internal medicine interns have poor knowledge about PAD including its prevalence, screening, treatment, and outcomes. Increased education during medical school is encouraged. PMID- 22297039 TI - Assessment of the infiltration of inflammatory cells in the walls of thrombotic varicose veins. AB - The purpose of this study is to describe the infiltration of mast cells as well as T and B cells in the walls of thrombotic varicose great saphenous veins. Sections were obtained from venous segments of patients with varicose veins and stained with toluidine blue for mast cells, while immunohistochemistry for T cells (using CD45RO antibody) and B cells (CD20) was analyzed using light microscopy after staining. The number of mast cells, T, and B cells observed in thrombotic varicose veins was 1.925 +/- 1.203, 72.038 +/- 34.707, and 19.519 +/- 9.899, respectively. In varicose veins, the corresponding values were 0.265 +/- 0.099, 0.600 +/- 0.432, and 0.488 +/- 0.400. Significantly higher number of mast cells, T cells, and B cells were observed in thrombotic varicose veins compared with control veins. A significant difference was not observed between the varicose group and control group. Thrombi in varicose veins can induce infiltration of mast cells, T cells, and B cells, which may be involved in the remodeling of venous walls. PMID- 22297040 TI - Mean platelet volume in patients with dilated cardiomyopathy: does it have a role in left ventricular thrombus formation? AB - We assessed the clinical echocardiograhic, hematological, and biochemical parameters in patients with dilated cardiomyopathy (DCMP) and control individuals mainly focusing on the mean platelet volume (MPV) in terms of DCMP and left ventricle (LV) thrombus formation. Consecutive patients (n = 251) with DCMP and 266 patients without DCMP were studied. Mean platelet volume was significantly greater in patients with DCMP than in control patients (P < .05 for all comparisons). Comparing DCMP patients with LV thrombus (19 patients, 8%) and without LV thrombus (232 patients, 92%) showed that the prevalence of smokers was significantly higher and ejection fraction was significantly lower in patients with LV thrombus. We have shown that patients with DCMP have significantly higher MPV suggesting more platelet activation and the MPV of patients with DCMP and LV thrombus is comparable to those of patients without LV thrombus. PMID- 22297041 TI - Acute intermittent hypoxia-induced expression of brain-derived neurotrophic factor is disrupted in the brainstem of methyl-CpG-binding protein 2 null mice. AB - Rett syndrome is a neurodevelopmental disorder caused by loss-of-function mutations in the gene encoding the transcription factor methyl-CpG-binding protein 2 (MeCP2). One of its targets is the gene encoding brain-derived neurotrophic factor (bdnf). In vitro studies using cultured neurons have produced conflicting results with respect to the role of MeCP2 in BDNF expression. Acute intermittent hypoxia (AIH) induces plasticity in the respiratory system characterized by long-term facilitation of phrenic nerve amplitude. This paradigm induces an increase in BDNF protein. We hypothesized that AIH leads to augmentation of BDNF transcription in respiratory-related areas of the brainstem and that MeCP2 is necessary for this process. Wild-type and mecp2 null (mecp2( /y)) mice were subjected to three 5-min episodes of exposure to 8% O(2)/4% CO(2)/88% N(2), delivered at 5-min intervals. Normoxia control wild-type and mecp2 null mice were exposed to room air for the total length of time, that is, 30 min. Following a recovery in room air, the pons and medulla were rapidly removed. Expression of BDNF protein and transcripts were determined by ELISA and quantitative PCR, respectively. AIH induced a significant increase in BDNF protein in the pons and medulla, and in mRNA transcript levels in the pons of wild-type animals. In contrast, there were no significant changes in either BDNF protein or transcripts in the pons or medulla of mice lacking MeCP2. The results indicate that MeCP2 is required for regulation of BDNF expression by acute intermittent hypoxia in vivo. PMID- 22297042 TI - Green synthesis of gold nanoparticles using palm oil mill effluent (POME): a low cost and eco-friendly viable approach. AB - The present study reports the synthesis of gold nanoparticles (AuNps) from gold precursor using palm oil mill effluent (POME) without adding external surfactant, capping agent or template. The biosynthesized AuNps were characterized by using UV-vis spectroscopy, transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). According to the image analysis performed on a representative TEM micrograph by counting 258 particles, the obtained AuNps are predominantly spherical with an average size of 18.75 +/- 5.96 nm. In addition, some triangular and hexagonal nanoparticles were also observed. The influence of various reaction parameters such as reaction pH, concentration of gold precursor and interaction time to the morphology and size of biosynthesized AuNps was investigated. This study shows the feasibility of using agro waste material for the biosynthesis of AuNps which is potentially more scalable and economic due to its lower cost. PMID- 22297043 TI - Analysis of neofructooligosaccharides production mediated by the extracellular beta-fructofuranosidase from Xanthophyllomyces dendrorhous. AB - The extracellular beta-fructofuranosidase Xd-INV from the yeast Xanthophyllomyces dendrorhous mainly synthesizes the neo-fructooligosaccharides (neo-FOS) neokestose and neonystose. This enzyme is a glycoprotein with a content of 59-67% N-linked carbohydrates and an estimated molecular mass of 160-200 kDa. The extent level of glycosylation affects the thermal behaviour of the enzyme but not its hydrolase and transferase activities, which are optimal at 60-70 degrees C. The neo-FOS yield of this enzyme was increased from 40 to 168 g/L when the sucrose concentration increased from 420 to 600 g/L and when the reaction was carried out at 60 degrees C. The neo-FOS levels obtained (168 g/L) in this work are the largest reported for any microbial beta-fructofuranosidase. PMID- 22297044 TI - Gasification of rice straw in a fluidized-bed gasifier for syngas application in close-coupled boiler-gasifier systems. AB - The feasibility and operation performance of the gasification of rice straw in an atmospheric fluidized-bed gasifier was studied. The gasification was carried out between 700 and 850 degrees C. The stoichiometric air-fuel ratio (A/F) for rice straw was 4.28 and air supplied was 7-25% of that necessary for stoichiometric combustion. Mass and power balances, tar concentration, produced gas composition, gas phase ammonia, chloride and potassium concentrations, agglomeration tendencies and gas efficiencies were assessed. Agglomeration was avoided by replacing the normal alumina-silicate bed by a mixture of alumina-silicate sand and MgO. It was shown that it is possible to produce high quality syngas from the gasification of rice straw. Under the experimental conditions used, the higher heating value (HHV) of the produced gas reached 5.1 MJ Nm(-3), the hot gas efficiency 61% and the cold gas efficiency 52%. The obtained results prove that rice straw may be used as fuel for close-coupled boiler-gasifier systems. PMID- 22297045 TI - Use of mid- and near-infrared spectroscopy to track degradation of bio-based eating utensils during composting. AB - Near-infrared spectroscopy (NIRS) and mid-infrared spectroscopy (MIRS) have been used for quantitative and/or qualitative analysis of a wide range of materials. The objective of this study was to investigate the potential of MIRS and NIRS for following the degradation of bio-based food utensils during composting. Polylactide (PLA)-based forks lost 34% of their initial mass and were reduced to small friable fragments after 7 weeks of composting. NIRS and MIRS spectra of forks that were incubated for 7 weeks were nearly identical to spectra of untreated forks. NIRS and MIRS were more useful in following the degradation of a starch/polypropylene (PP) polymer. Spectral results demonstrated that the starch component degraded during composting and that the PP component was recalcitrant. These results confirm that MIRS and NIRS are useful in determining the composition of biobased materials. However, the spectra did not provide useful information about the extent of PLA polymer degradation. PMID- 22297046 TI - Characterisation of palm empty fruit bunch (PEFB) and pinewood bio-oils and kinetics of their thermal degradation. AB - Ultimate and proximate analyses and thermal degradation of bio-oils from pinewood and palm empty fruit bunches (PEFB) were carried out to evaluate the oils' potential for production of fuels for transport, heat and power generation, and of hydrogen via the calculation of performance indicators. The pinewood and PEFB oils indicated good theoretical hydrogen yields of 13.7 and 15.9 wt.% via steam reforming, but their hydrogen to carbon effective ratios were close to zero, and their propensity for fouling and slagging heat exchanger surfaces via combustion was high. Both oils exhibited two phases during mass loss under nitrogen flow at heating rates of 3-9 Kmin(-1), but the kinetics of their thermal degradation from TGA-FTIR analysis indicated different degradation mechanisms that were well reproduced by a nth order reaction model for pinewood and Jander's 3D-diffusion model for PEFB. These findings lead to recommendations on pretreatments prior to the oils' utilisation. PMID- 22297047 TI - Mixotrophic operation of photo-bioelectrocatalytic fuel cell under anoxygenic microenvironment enhances the light dependent bioelectrogenic activity. AB - Electrogenic activity of photo-bioelectrocatalytic /photo-biological fuel cell (PhFC) was evaluated in a mixotrophic mode under anoxygenic microenvironment using photosynthetic consortia as biocatalyst. An acetate rich wastewater was used as anolyte for harnessing energy along with additional treatment. Mixotrophic operation facilitated good electrogenic activity and wastewater treatment associated with biomass growth. PhFC operation documented feasible microenvironment for the growth of photosynthetic bacteria compared to algae which was supported by pigment (total chlorophyll and bacteriochlorophyll) and diversity analysis. Pigment data also illustrated the association between bacterial and algal species. The synergistic interaction between anoxygenic and oxygenic photosynthesis was found to be suitable for PhFC operation. Light dependent deposition of electrons at electrode was relatively higher compared to dark dependent electron deposition under anoxygenic condition. PhFC documented for good volatile fatty acids removal by utilizing them as electron donor. Bioelectrochemical behavior of PhFC was evaluated by voltammetric and chronoamperometry analysis. PMID- 22297048 TI - Thermogravimetric-mass spectrometric analysis of lignocellulosic and marine biomass pyrolysis. AB - The pyrolysis characteristics of three lignocellulosic biomasses (fir wood, eucalyptus and pine bark) and a marine biomass (Nannochloropsis gaditana microalgae) were investigated by thermogravimetric analysis coupled with mass spectrometry (TGA-MS). Thermal degradation of lignocellulosic biomass was divided into four zones, corresponding to the decomposition of their main components (cellulose, hemicellulose and lignin) and a first step associated to water removal. Differences in volatile matter and cellulose content of lignocellulosic species resulted in different degradation rates. Microalgae pyrolysis occurred in three stages due to the main components of them (proteins), which are greatly different from lignocellulosic biomass. Heating rate effect was also studied. The main gaseous products formed were CO(2), light hydrocarbons and H(2)O. H(2) was detected at high temperatures, being associated to secondary reactions (char self gasification). Pyrolysis kinetics were studied using a multiple-step model. The proposed model successfully predicted the pyrolytic behaviour of these samples resulting to be statistically meaningful. PMID- 22297049 TI - Comparative evaluation of autohydrolysis and acid-catalyzed hydrolysis of Eucalyptus globulus wood. AB - Three different acids (acetic, oxalic and sulfuric acid) were tested for their catalytic activity during the pretreatment of Eucalyptus globulus wood comparatively to autohydrolysis in order to extract valuable products prior to kraft pulping and to reduce lignin precipitation in the pretreatment step. The utilization of oxalic and sulfuric acid reduces treatment temperatures at a given wood yield as compared to autohydrolysis and acetic acid addition and thus decreases the insoluble lignin content in the hydrolyzates. Due to the high temperatures of autohydrolysis xylose dehydration to furfural occurs at high wood yield losses, while during acid catalyzed hydrolysis degradation of cellulose to glucose is more pronounced. The main difference between the acid catalyzed and non-catalyzed reaction constitutes the ratio of monomeric xylose and xylooligosaccharides in solution. PMID- 22297050 TI - Optimization of furfural and 5-hydroxymethylfurfural production from wheat straw by a microwave-assisted process. AB - Optimization of acid-catalyzed conversion conditions of wheat straw into furfural, 5-hydroxymethylfurfural (HMF), glucose, and xylose was studied by response surface methodology (RSM). A central composite design (CCD) was used to determine the effects of independent variables, including reaction temperature (140-200 degrees C), residence time (1-41 min), pH (0.1-2.1), and liquid:solid ratio (15-195 mL/g) on furan and sugar production. The surface response analysis revealed that temperature, time and pH had a strong influence on the furfural, HMF, xylose and glucose yield, whereas liquid to solid ratio was found not to be significant. The initial pH of solution was the most important variable in acid catalyzed conversion of wheat straw to furans. The maximum predicted furfural, HMF, xylose and glucose yields were 66%, 3.4%, 100%, and 65%, respectively. This study demonstrated that the microwave-assisted process was a very effective method for the xylose production from wheat straw by diluted acid catalysis. PMID- 22297051 TI - Brain cancer prognosis: independent validation of a clinical bioinformatics approach. AB - Translational and evidence based medicine can take advantage of biotechnology advances that offer a fast growing variety of high-throughput data for screening molecular activities of genomic, transcriptional, post-transcriptional and translational observations. The clinical information hidden in these data can be clarified with clinical bioinformatics approaches. We have recently proposed a method to analyze different layers of high-throughput (omic) data to preserve the emergent properties that appear in the cellular system when all molecular levels are interacting. We show here that this method applied to brain cancer data can uncover properties (i.e. molecules related to protective versus risky features in different types of brain cancers) that have been independently validated as survival markers, with potential important application in clinical practice. PMID- 22297052 TI - Preoperative ultrasonography findings predict the need for repeated surgery in papillary thyroid cancer. AB - OBJECTIVE: To determine the impact of neck ultrasonography in predicting papillary thyroid cancer persistence or recurrence. METHODS: Between March 2005 and March 2009, we identified patients with a preoperative diagnosis of papillary thyroid cancer. Exclusion criteria included no documented preoperative ultrasonography and initial surgery at an outside institution. Patients with positive preoperative ultrasonography were compared with patients who had negative preoperative ultrasonography by assessing rates of neck dissection, complications, disease persistence or recurrence, and the need for repeated surgery. RESULTS: Of 127 patients initially identified, 16 did not have preoperative ultrasonography and 4 did not have their initial surgery at our institution, leaving 107 patients in our cohort. Twenty-two patients had positive preoperative ultrasonography and 85 patients had negative preoperative ultrasonography. Patients with positive preoperative ultrasonography had a higher rate of repeated surgery than those with negative preoperative ultrasonography (27% vs 4.7%, P = .003). There was no difference in postoperative complication rates. No patients with negative preoperative ultrasonography and an ultrasound report stating specifically "no suspicious lymph nodes" required repeated surgery. CONCLUSIONS: Negative preoperative ultrasonography with specific lymph node evaluation predicts a low risk of needing early reoperation. Positive preoperative ultrasonography may be a marker for more aggressive disease and the best predictor of the need for additional surgery in the future. PMID- 22297053 TI - Does subclinical hyperthyroidism predispose to cocaine addiction? AB - OBJECTIVE: To investigate the relationship between subclinical hyperthyroidism and cocaine abuse. METHODS: Using the computerized patient medical record system at the Veterans Affairs Medical Center in Memphis, Tennessee, we identified the following 3 groups: (1) cocaine abusers without hyperthyroidism; (2) patients with hyperthyroidism without cocaine abuse; and (3) patients with hyperthyroidism and cocaine abuse. In 1,191 patients taken from the same clinic population, we calculated the prevalence of cocaine abuse alone, hyperthyroidism alone, and both diagnoses together to examine whether a relationship existed between hyperthyroidism and cocaine abuse. RESULTS: We found the following prevalences: (1) 37.7 per 1,000 patients with cocaine abuse; (2) 18.8 per 1,000 with hyperthyroidism (primarily subclinical); and (3) 65.4 per 1,000 with both hyperthyroidism and cocaine abuse. We found a highly statistically significant correlation between subclinical hyperthyroidism and cocaine abuse (P<<.01 by chi2 test) in this population of Veterans Affairs patients. No other significant correlations were found. CONCLUSION: In our study population, we found a strong correlation between hyperthyroidism (overt or subclinical) and cocaine abuse. Several theoretical mechanisms may explain these findings, but further prospective studies are needed to clarify this complex relationship. PMID- 22297054 TI - Chromium infusion in hospitalized patients with severe insulin resistance: a retrospective analysis. AB - OBJECTIVE: To investigate the effects of intravenous chromium on serum glucose and insulin infusion rates in hospitalized patients with severe insulin resistance. METHODS: In this retrospective study, we reviewed hospital records from January 1, 2008, to December 1, 2008, to identify patients for whom intravenous chromium was ordered at our academic medical center. To be included, patients were required to demonstrate profound insulin resistance and uncontrolled hyperglycemia (defined as the inability to achieve a blood glucose value less than 200 mg/dL during the 12 hours before chromium was given despite administration of continuous insulin infusion at a rate of 20 or more units/h) and to have received a continuous infusion of chromium chloride at 20 mcg/h for 10 to 15 hours for a total dose of 200 to 240 mcg. RESULTS: Fourteen patients met our inclusion criteria. Over the hour preceding intravenous chromium infusion, the mean +/- standard deviation rate of insulin infusion was 31 +/- 15 units/h, and blood glucose was 326 +/- 86 mg/dL. Twelve hours after the initiation of chromium, these values were 16 +/- 16 units/h and 162 +/- 76 mg/dL, respectively (P = .011 for difference in mean insulin rate from baseline, P<.001 for difference in mean blood glucose from baseline) and 24 hours after, these values were 12 +/- 15 units/h and 144 +/- 48 mg/dL, respectively (P<.001 for both). CONCLUSIONS: Intravenous chromium decreases insulin needs and improves glucose control at 12 and 24 hours compared with baseline values. Chromium appears to improve hyperglycemia and insulin resistance in acutely ill patients and represents a potential new therapy. Future prospective randomized controlled trials are needed to confirm these results. PMID- 22297055 TI - Continuous subcutaneous infusion of insulin lispro in children and adolescents with type 1 diabetes mellitus. AB - OBJECTIVE: To provide a comprehensive review of insulin lispro administered by continuous subcutaneous insulin infusion (CSII) in children and adolescents. METHODS: We performed PubMed literature searches to identify clinical studies of insulin lispro administered via CSII within pediatric and adolescent populations. RESULTS: Twenty-six studies involving 2521 pediatric patients with type 1 diabetes mellitus met inclusion criteria. Of these, 10 were randomized controlled trials (RCTs), 6 of which compared insulin lispro CSII with multiple daily injection (MDI) therapy. We identified 7 additional prospective, nonrandomized studies and 9 retrospective studies. Within the RCTs, endpoint hemoglobin A1c levels ranged from 6.3% to 8.5% for insulin lispro CSII therapy and from 6.2% to 8.7% for those trials with MDI comparator arms. In those trials that compared insulin lispro CSII with MDI, the endpoint hemoglobin A1c achieved with insulin lispro was similar or improved compared with observations in the MDI treatment arm. In the RCTs, severe hypoglycemia rates of 0.1 to 0.3 episodes/patient per year were reported for insulin lispro CSII therapy; those trials with MDI comparator arms reported relatively similar severe hypoglycemia rates (0.1 to 0.5 episodes/patient per year). Events of diabetic ketoacidosis (DKA) were rare. Where reported, insulin lispro CSII and MDI therapy demonstrated a similar occurrence of DKA and incidence of severe hypoglycemia. Prospective and retrospective studies demonstrated results similar to the RCT findings. CONCLUSIONS: In 26 studies of more than 2500 pediatric and adolescent patients with type 1 diabetes, with more than 1000 patients specifically receiving insulin lispro CSII, insulin lispro CSII therapy consistently demonstrated similar or improved efficacy and safety vs studied comparators. PMID- 22297056 TI - Creatine kinase elevation, lactacidemia, and metabolic myopathy in adult patients with diabetes mellitus. AB - OBJECTIVE: To determine the frequency of elevated creatine kinase (CK) levels among patients with diabetes mellitus and to determine how often elevated CK is attributable to primary myopathy. METHODS: In this prospective study, we investigated how often CK, aspartate amino-transferase, alanine aminotransferase, and resting lactate were elevated among consecutive diabetic patients attending our clinic. Those with elevated CK values were offered a neurologic workup. RESULTS: Ninety-nine patients with diabetes mellitus, aged 19 to 87 years, were assessed between May 2008 and April 2010. Seven patients had type 1 diabetes and 92 patients had type 2 diabetes. CK, aspartate aminotransferase, alanine aminotransferase, and resting lactate were elevated in 19 of 99, 25 of 99, 22 of 99, and 24 of 98 patients, respectively. Eleven of 19 patients with increased CK were self-injecting insulin. Ten of 24 patients with elevated serum lactate took metformin. Seven of 19 patients with elevated CK consented to neurologic workup. Two of the 7 had elevated resting lactate. In all 7 patients, the findings from neurologic investigation were indicative of a metabolic defect and further diagnostic evaluation was recommended. CONCLUSIONS: In diabetic patients attending our clinic, elevated CK levels occur in one-fifth and lactacidemia occurs in one-quarter. Elevated CK levels are attributable to a primary metabolic myopathy in most cases. Elevated CK levels in the setting of diabetes mellitus require further neurologic evaluation. PMID- 22297057 TI - Cardiac complications as initial manifestation of pheochromocytoma: frequency, outcome, and predictors. AB - OBJECTIVE: To examine the frequency, outcome, and clinical predictors of cardiac complications as the initial manifestation of pheochromocytoma. METHODS: The medical records of all 76 patients with pheochromocytoma or functional paraganglioma treated at Cedars-Sinai Medical Center, Los Angeles, California, from 1995 to 2011 were reviewed. The patients initially presenting with cardiac complications were identified, and their clinical, laboratory, and imaging characteristics were compared with those of the patients presenting with other complaints, especially hypertension and adrenal mass. RESULTS: Of the 76 patients, 9 (12%) presented with the following: 2 with acute heart failure, 1 with left ventricular thrombus, 3 with myocardial infarction, and 3 with severe arrhythmia. Failure to diagnose pheochromocytoma resulted in unnecessary invasive interventions in 2 patients. Recovery of cardiac function was excellent after resection of the tumor in all patients. In comparison with the 67 patients presenting with other complaints, the 9 with cardiac complications had similar demographics and cardiac risk factors but harbored larger tumors (6.7 +/- 0.8 cm versus 4.4 +/- 0.3 cm; P = .015) and exhibited higher biochemical marker levels (23.9 +/- 9.0-fold versus 11.3 +/- 2.4-fold; P = .082), longer corrected QT interval (473 +/- 8 ms versus 443 +/- 6 ms; P = .015), and lower ejection fraction (43% +/- 8% versus 66% +/- 2%; P = .002). CONCLUSION: In this study, 12% of patients with pheochromocytoma initially presented with cardiac complications. Patients with large tumors and high levels of biochemical markers were more likely to develop cardiac injury. Our results confirm that the presence of pheochromocytoma should be ruled out in patients with cardiac diseases and features suggesting pheochromocytoma so that unnecessary interventions can be avoided and cardiac recovery can be achieved. PMID- 22297058 TI - Delayed anithyroid drug-induced agranulocytosis. AB - OBJECTIVE: To demonstrate that drug-induced agranulocytosis can occur after a very prolonged period of low-dose treatment with antithyroid medications. METHODS: We present the history and long-term follow-up of a patient with Graves disease, including clinical and laboratory findings, and provide a brief review of the related literature. RESULTS: A 53-year-old woman with a history of Graves disease presented with an absolute neutrophil count of zero, body temperature of 38.7 degrees C, and symptoms of an upper respiratory tract infection. She had been treated continuously with low doses of antithyroid drugs for the preceding 11 years-propylthiouracil (100 to 150 mg daily) from February 1998 until July 2003 and methimazole (5 to 30 mg daily) from July 2003 until her presentation with severe neutropenia in March 2009. The daily dose of methimazole had been stable at 15 mg for 1 year before the current presentation. A thorough hematologic evaluation, including bone marrow biopsy, did not reveal an alternative cause for the agranulocytosis. After discontinuation of methimazole treatment and a short course of granulocyte colony-stimulating factor, she responded successfully with clinical improvement of her symptoms and resolved neutropenia. CONCLUSION: Although this case is atypical, it reinforces the importance of remaining vigilant for signs of agranulocytosis throughout the course of treatment with antithyroid drugs, even at low doses and after years of continuous administration. PMID- 22297059 TI - Sitagliptin in glutamic acid decarboxylase antibody-positive diabetes mellitus. AB - OBJECTIVE: To describe a case illustrating the use of sitagliptin, an inhibitor of dipeptidyl-peptidase-4 (DPP-4), in anti-glutamic acid decarboxylase antibody positive diabetes mellitus in association with a rare ataxic variant of stiff person syndrome. METHODS: We present our experience with use of the DPP-4 inhibitor sitagliptin for management of autoimmune diabetes in a elderly woman and highlight the association of diabetes with other autoimmune conditions. RESULTS: A 68-year-old Japanese woman presented with poorly controlled "type 2" diabetes mellitus, cerebral palsy, cerebellar ataxia, and hypothyroidism. She complained of stiffness and spasms, which had resulted in multiple falls and immobility. Antidiabetic medications included gliclazide, rosiglitazone, and acarbose; various insulins had been tried but discontinued because they worsened her stiffness and spasms. Her hemoglobin A1c values remained above 9% despite maximal doses of the aforementioned orally administered hypoglycemic agents. After sitagliptin therapy was initiated, her hemoglobin A1c level decreased from 9.3% (78 mmol/mol) to 7.3% (56 mmol/mol) in 5 months. Investigations confirmed the presence of an ataxic variant of stiff person syndrome. On repeated testing 18 months later, her anti-glutamic acid decarboxylase antibody levels had declined by more than 85%. CONCLUSION: Apart from the well-known mechanism of an increase in glucagonlike peptide-1, sitagliptin may exert its glucose-lowering effect by other mechanisms in patients with autoimmune diabetes. Further studies should be undertaken to address the effectiveness of DPP-4 inhibitors in non-type 2 diabetes. PMID- 22297060 TI - Association of dengue hemorrhagic fever with multiple risk factors for pituitary apoplexy. AB - OBJECTIVE: To describe pituitary apoplexy that developed during the course of dengue hemorrhagic fever. METHODS: We describe the clinical findings, laboratory test results, imaging findings, and clinical course of the study patients. RESULTS: Patient 1 was a 40-year-old man who developed clinical signs and symptoms of dengue, which was confirmed by serologic testing. He presented with thrombocytopenia and developed severe headache and vomiting. During hospitalization, acromegaly was suspected because of the characteristic disease phenotype. Magnetic resonance imaging confirmed the diagnosis of pituitary apoplexy. Subsequently, the biochemical diagnosis of acromegaly was confirmed, and the patient underwent transsphenoidal surgery. Histopathologic examination showed signs of recent bleeding. Patient 2 was a 38-year-old man with a macroprolactinoma, who had been treated with cabergoline for 10 weeks and had shown improvement on laboratory testing and imaging. The patient then presented with clinical symptoms of dengue (confirmed serologically) and thrombocytopenia. He developed bilateral hemianopsia, and magnetic resonance imaging showed enlargement of the pituitary adenoma with signs of intratumoral bleeding. The patient underwent transsphenoidal surgery, and histopathologic examination documented a pituitary adenoma diffusely infiltrated by blood cells. CONCLUSIONS: We describe dengue as a probable novel condition for pituitary apoplexy because it may be associated with multiple risk factors for pituitary infarction or bleeding. Physicians should suspect pituitary apoplexy in patients with dengue hemorrhagic fever who develop a rapid onset of severe headache and vision defects, even in those without known pituitary adenomas. PMID- 22297061 TI - Late manifestation of tracheal rupture after thyroidectomy: case report and literature review. AB - OBJECTIVE: To report an extremely rare case of delayed tracheal rupture after thyroidectomy and to review the existing related literature. METHODS: We present the history, clinical findings, radiographic evaluation, management, and intraoperative findings in a patient who presented with subcutaneous emphysema 9 days after total thyroidectomy. In addition, we review the literature and discuss the diagnostic challenges as well as management options. RESULTS: A 17-year-old female patient underwent a total thyroidectomy for Graves disease. On postoperative day 9, the patient presented with face and neck swelling attributable to subcutaneous emphysema. After conservative management failed, the patient underwent surgical exploration of the neck, which revealed a 2.5-cm linear vertical tear in the anterior aspect of the trachea, with no evidence of necrosis. The tear had viable edges and was primarily repaired with use of muscle flap reinforcement. The patient recovered with no other complications. CONCLUSION: Delayed tracheal rupture should be suspected in all patients who present with subcutaneous emphysema after a thyroid surgical procedure. Review of the pertinent literature suggests that conservative management is suitable in patients with a stable condition. Surgical repair is indicated in those patients who fail to demonstrate clinical improvement. PMID- 22297066 TI - Evidence for fractional anisotropy and mean diffusivity white matter abnormalities in the internal capsule and cingulum in patients with obsessive compulsive disorder. AB - BACKGROUND: There is evidence to suggest that obsessive-compulsive disorder (OCD) is associated with structural abnormalities in cortico-striato-thalamic circuits, yet the extent of white matter abnormalities is not well established. In this study, we used diffusion tensor imaging (DTI) to examine white matter integrity in specific regions of interest (ROIs) in patients with OCD. METHODS: Patients with OCD and sex-, age- and IQ-matched healthy controls underwent DTI. The primary objective was to explore whether patients with OCD had white matter abnormalities in the anterior limb of the internal capsule (ALIC), the uncinate fasciculus, the genu of the corpus callosum and the cingulum. The secondary objective was to evaluate the relation between fractional anisotropy and mean diffusivity in these ROIs and other clinical variables (including age at onset of OCD, OCD severity and levels of depressive and anxiety symptomatology) in patients with OCD. RESULTS: There were 15 patients and 17 controls enrolled in our study. Compared with healthy controls, patients with OCD showed increased fractional anisotropy in bilateral regions of the ALIC adjacent to the body of the caudate, as well as decreased fractional anisotropy in the right anterior limb near the head of the caudate. Patients also had decreased mean diffusivity in the body of the right cingulum and the left anterior cingulum compared with controls. Correlational analyses revealed significant associations of fractional anisotropy and mean diffusivity in select circuits with OCD, depression and anxiety severity scores. LIMITATIONS: Inclusion of patients with OCD receiving pharmacotherapy may have been a limitation. In addition, the patients were heterogeneous in terms of their obsessive-compulsive symptom profiles; we did not distinguish between different obsessive-compulsive symptom dimensions. CONCLUSION: The study results provide further evidence for OCD-related white matter abnormalities in the ALIC and cingulum, consistent with a cortico striatal model of OCD. PMID- 22297067 TI - Mapping vulnerability to bipolar disorder: a systematic review and meta-analysis of neuroimaging studies. AB - BACKGROUND: Although early interventions in individuals with bipolar disorder may reduce the associated personal and economic burden, the neurobiologic markers of enhanced risk are unknown. METHODS: Neuroimaging studies involving individuals at enhanced genetic risk for bipolar disorder (HR) were included in a systematic review. We then performed a region of interest (ROI) analysis and a whole-brain meta-analysis combined with a formal effect-sizes meta-analysis in a subset of studies. RESULTS: There were 37 studies included in our systematic review. The overall sample for the systematic review included 1258 controls and 996 HR individuals. No significant differences were detected between HR individuals and controls in the selected ROIs: striatum, amygdala, hippocampus, pituitary and frontal lobe. The HR group showed increased grey matter volume compared with patients with established bipolar disorder. The HR individuals showed increased neural response in the left superior frontal gyrus, medial frontal gyrus and left insula compared with controls, independent from the functional magnetic resonance imaging task used. There were no publication biases. Sensitivity analysis confirmed the robustness of these results. LIMITATIONS: As the included studies were cross-sectional, it remains to be determined whether the observed neurofunctional and structural alterations represent risk factors that can be clinically used in preventive interventions for prodromal bipolar disorder. CONCLUSION: Accumulating structural and functional imaging evidence supports the existence of neurobiologic trait abnormalities in individuals at genetic risk for bipolar disorder at various scales of investigation. PMID- 22297065 TI - Systematic review of the neural basis of social cognition in patients with mood disorders. AB - BACKGROUND: This review integrates neuroimaging studies of 2 domains of social cognition--emotion comprehension and theory of mind (ToM)--in patients with major depressive disorder and bipolar disorder. The influence of key clinical and method variables on patterns of neural activation during social cognitive processing is also examined. METHODS: Studies were identified using PsycINFO and PubMed (January 1967 to May 2011). The search terms were "fMRI," "emotion comprehension," "emotion perception," "affect comprehension," "affect perception," "facial expression," "prosody," "theory of mind," "mentalizing" and "empathy" in combination with "major depressive disorder," "bipolar disorder," "major depression," "unipolar depression," "clinical depression" and "mania." RESULTS: Taken together, neuroimaging studies of social cognition in patients with mood disorders reveal enhanced activation in limbic and emotion-related structures and attenuated activity within frontal regions associated with emotion regulation and higher cognitive functions. These results reveal an overall lack of inhibition by higher-order cognitive structures on limbic and emotion-related structures during social cognitive processing in patients with mood disorders. Critically, key variables, including illness burden, symptom severity, comorbidity, medication status and cognitive load may moderate this pattern of neural activation. LIMITATIONS: Studies that did not include control tasks or a comparator group were included in this review. CONCLUSION: Further work is needed to examine the contribution of key moderator variables and to further elucidate the neural networks underlying altered social cognition in patients with mood disorders. The neural networks under lying higher-order social cognitive processes, including empathy, remain unexplored in patients with mood disorders. PMID- 22297068 TI - Differential association between the norepinephrine transporter gene and ADHD: role of sex and subtype. AB - BACKGROUND: Pharmacologic and animal studies have strongly implicated the norepinephrine transporter (NET) in the pathophysiology of attention deficit/hyperactivity disorder (ADHD). We conducted a family-based study, with stratification based on sex and subtype, to test the association between 30 tag single-nucleotide polymorphisms (SNPs) within the gene encoding NET (SLC6A2) and ADHD. METHODS: Family-based association tests were conducted with the categorical diagnosis of ADHD, as well as quantitative phenotypes of clinical relevance (Conners Global Index for Teachers and Parents, and Child Behavior Checklist measures). Sliding window haplotype analysis was conducted with screening based on conditional power using PBAT. RESULTS: A previously reported association with rs3785143 was confirmed in this study. Further, extensive association was observed with haplotype blocks, with a differential pattern observed based on sex and subtype. The 5' region of the gene (encompassing haplotype block 1 and including a functional promoter SNP, rs28386840) showed an association with ADHD in girls (irrespective of subtype). A different region of the gene (distributed around haplo-type block 2) was associated with distinct behavioural phenotypes in boys. These findings are correlated with previously reported functional studies of gene variants in SLC6A2. LIMITATIONS: The most important limitation of the study is the small size of the groups resulting from the stratification based on sex followed by subtype. CONCLUSION: The results obtained in this family-based study suggest that haplotype blocks within different regions of SLC6A2 show differential association with the disorder based on sex and subtype. These associations may have been masked in previous studies when tests were conducted with pooled samples. PMID- 22297069 TI - [Prefabricated flaps using collagen substitute: a new technique for the future?]. AB - Collagen substitutes represent a good option for burn scars release. Authors describe a new technique using prefabricated flap associated with collagen substitute. This technique is illustrated by a scar contracture removal on a young child located on the dorsum of the hand and wrist using a pedicle axial flap and a collagen substitute. Neo-collagen prefabricated flap is a new sophisticated surgical technique regarding the flap technique due to the possibility to create by patient cells themselves neo-fashioned flaps much more adapted to the recipient site and decreasing sequels on the donor site. PMID- 22297070 TI - The possible role of ribosomal protein S6 kinase 4 in the senescence of endothelial progenitor cells in diabetes mellitus. AB - BACKGROUND: The decrease and dysfunction of endothelial progenitor cells (EPCs) has been assumed as an important cause/consequence of diabetes mellitus (DM) and its complications, in which the senescence of EPCs induced by hyperglycemia may play an immensurable role. However, the mechanisms of EPCs senescence has not been fully investigated. Recently, ribosomal protein S6 kinase 4 (RSK4), a member of serine/threomine (Ser/Thr) kinase family and p53-related gene, is reported to regulate the replicative and stress-induced senescence of different cells. PRESENTATION OF THE HYPOTHESIS: These above lead to consideration of an evidence based hypothesis that RSK4 may serve as a mediator of EPCs senescence in DM. TESTING THE HYPOTHESIS: EPCs of healthy subjects and DM patients are isolated from peripheral blood and incubated with high glucose (HG). Then, the EPCs senescence would be detected by senescence associated beta-galactosides (SA-beta gal) staining. Meanwhile, the RSK4 expression is assessed by RT-PCR and western blot. Moreover, overexpressing or RNA interfering of RSK4 in EPCs to investigate the relationship between RSK4 expression and the senescence of EPCs are necessary to substantiate this hypothesis. Also, studies on possible upstream and downstream factors of RSK4 would be explored to reveal the RSK4-mediated senescence pathway in EPCs. IMPLICATIONS OF THE HYPOTHESIS: If proved, this hypothesis will provide another mediator of EPCs senescence, and may establish a novel pathogenesis for DM and further benefit to the management of DM. PMID- 22297071 TI - Claudin-1 and glucose transporter 1 immunolabelling in a canine intraneural perineurioma. AB - A 4-year-old male leonberger was diagnosed tentatively with a peripheral nerve sheath tumour of the median nerve based on neurological examination, electrodiagnostic testing and ultrasound evaluation. The lesion was excised and submitted for pathological examination. Histopathology revealed an irregularly enlarged, hypercellular nerve fascicle with neoplastic tissue consisting of a uniform population of spindle-shaped cells arranged in 'pseudo-onion bulb-like' whorls around axons. Minimal anisocytosis and anisokaryosis were present, together with a low mitotic index. Electron microscopy showed spindle cells with a discontinuous basal membrane and intercellular junctions, as well as pinocytotic vesicles. Immunohistochemistry for neurofilament, S100 and glucose transporter 1 was negative, whereas labelling for claudin-1 and laminin was positive. Based on these observations, a definitive diagnosis of intraneural perineurioma was made. PMID- 22297072 TI - Possible role of Snail expression as a prognostic factor in canine mammary neoplasia. AB - Epithelial cells adhere tightly to each other by cell-to-cell adhesion and through the basement membrane barrier to prohibit movement. In carcinomas, neoplastic epithelial cells lose their epithelial characteristics and acquire a mesenchymal phenotype during the epithelial-mesenchymal transition (EMT) for invasion and metastasis. The aim of this study was to identify Snail expression and examine the role of Snail protein in canine mammary tumour progression. Immunohistochemical expression of Snail, E-cadherin, oestrogen receptor, human epidermal growth factor receptor-2, cytokeratin 14 and p63 was analyzed in 54 samples of canine mammary epithelial tumours (11 adenomas and 43 carcinomas). Expression of mRNA encoding Snail was evaluated in seven samples (one normal mammary gland, two adenomas and four carcinomas) by reverse transcriptase polymerase chain reaction. Snail mRNA was detected in all samples. Snail expression correlated significantly with histological type, grade and lymphatic invasion. However, there was no association between Snail expression and molecular subtype and between Snail expression and that of E-cadherin. Snail, a hallmark of EMT, might play an important role in invasion and metastasis of canine mammary carcinomas. PMID- 22297073 TI - Carcinoma of the trachea in a cat. AB - Non-keratinizing squamous cell carcinoma of the trachea was diagnosed in an 11 year-old domestic shorthaired cat suffering from progressive cough and dyspnoea. The tumour was characterized by immunohistochemical expression of cytokeratins and focal expression of vimentin. The cat was exposed historically to high concentrations of environmental cigarette smoke and this may have been a contributory aetiological factor in the genesis of this tumour. PMID- 22297074 TI - A review of the association between osteosarcoma metastasis and protein translation. AB - The malignant transformation of mesenchymal cells within the bone leads to the development of osteosarcoma (OS), but the genetic underpinnings of these events are not understood. From a clinical perspective, primary tumour management can be achieved successfully in most patients. However, the development of metastasis to the lungs represents the most common cause of death in OS patients. A clearer understanding of metastasis biology is required to improve cancer mortality and improve outcomes. Modelling the genetics, biology and therapy of OS can be accomplished through research involving a number of species. Most notable is the naturally occurring form of OS that develops in dogs. Through a cross-species and comparative approach important questions can be asked within specific and suitable models to advance our understanding of this disease and its common metastatic outcome. A comparative perspective on the problem of OS metastasis that utilizes a cross-species approach may offer unique opportunities to assist in this prioritization and generate new hypotheses related to this important clinical problem. PMID- 22297075 TI - Disseminated pleomorphic myofibrosarcoma in a grizzly bear (Ursus arctos horribilis). AB - The pathological and diagnostic features of a widely disseminated pleomorphic high-grade myofibroblastic sarcoma are described in a 23-year-old male brown bear (Ursus arctos horribilis). Firm, solid, white to tan neoplastic nodules, often with cavitated or soft grey-red necrotic centres, were observed throughout most internal organs, subcutaneous tissues and skeletal muscles on gross examination. Microscopically, the tumour consisted of pleomorphic spindle cells forming interlacing fascicles with a focal storiform pattern with large numbers of bizarre polygonal multinucleate cells, frequently within a collagenous stroma. Immunohistochemistry, Masson's trichrome stain and transmission electron microscopy designated the myofibroblast as the cell of origin. This is the first case of a high-grade myofibrosarcoma in a grizzly bear. PMID- 22297076 TI - Pathology and viral antigen distribution following experimental infection of sheep and goats with capripoxvirus. AB - Current understanding of capripoxvirus pathogenesis is limited since there have been no detailed studies examining cell tropism at well-defined intervals following infection. We undertook time-course studies in sheep and goats following inoculation of sheeppox or goatpox viruses in their respective homologous hosts, and examined tissues by light microscopy. A monoclonal antibody generated to a sheeppox virus core protein was used for immunohistochemical detection of viral antigen in tissue sections. Lesions and virus antigen were observed consistently in the skin, lung and lymph nodes. Antigen was detected at 6 and 8 days post inoculation for skin and lung, respectively, within cells which appeared to be of monocyte/macrophage lineage. In sheep skin capripoxvirus immunoreactivity was detected within previously unreported large multinucleated cells. In the lung, double immunolabelling detected the simultaneous expression of capripoxvirus antigen and cytokeratin indicating the presence of virus within pneumocytes. Lung double immunolabelling also detected the expression of capripoxvirus antigen in CD68(+) cells, confirming the presence of viral antigen within macrophages. Based on early detection of infected macrophages, dissemination of virus within the host and localization to tissues likely occurred through cells of the monocyte/macrophage lineage. Histological findings revealed similarities with both monkeypox and smallpox, thus capripoxvirus infection in sheep and goats may represent useful models with which to study strategies for poxvirus-specific virus vaccine concepts and therapeutics. PMID- 22297077 TI - Diagnostic value of morphometry in feline hypertrophic cardiomyopathy. AB - Hypertrophic cardiomyopathy (HCM) is the most common form of feline heart disease. To date, reliable morphometric reference data for anatomical or histological changes are unavailable. The aim of this study was to identify diagnostically relevant morphometric criteria that clearly distinguish feline HCM from normal hearts. Hearts from 15 cats with HCM had increased weights (g per distance between the first and eighth vertebral bodies) when compared with hearts from 15 matched control cats. Several anatomically defined and digitally scanned areas of standardized cross sections were significantly increased in HCM when compared with controls, including the area across the entire heart half-way between the coronary sulcus and apex, the right and left ventricular walls and the ventricular septum. Differences were similar when the papillary muscles were included in the measurements of the right and left ventricular walls and the ventricular septum. Histological morphometric analyses failed to identify any significant differences, including the diameter and cross-sectional area of cardiomyocytes and the length, width or areas of cross-sectioned nuclei. In addition, morphometric analyses failed to identify any differences in the amount of cardiomyocyte fibre branching or myocardial fibrosis. Thus, only the relative weight and macroscopical analyses proved useful in distinguishing feline hearts with HCM from normal hearts. The results do not uphold the hypothesis that increased cardiomyocyte diameter is a principal change in feline HCM. PMID- 22297078 TI - Giant primary adrenal hydatid cyst presenting with arterial hypertension: a case report and review of the literature. AB - INTRODUCTION: A primary hydatid cyst of the adrenal gland is still an exceptional localization. The adrenal gland is an uncommon site even in Morocco, where echinococcal disease is endemic. CASE PRESENTATION: We report the case of a 64 year-old Moroccan man who presented with the unusual symptom of arterial hypertension associated with left flank pain. Computed tomography showed a cystic mass of his left adrenal gland with daughter cysts filing the lesion (Type III). Despite his negative serology tests, the diagnosis of a hydatid cyst was confirmed on surgical examination. Our patient underwent surgical excision of his left adrenal gland with normalization of blood pressure. No recurrence has occurred after 36 months of follow-up. CONCLUSION: There are two remarkable characteristics of this case report; the first is the unusual location of the cyst, the second is the association of an adrenal hydatid cyst with arterial hypertension, which has rarely been reported in the literature. PMID- 22297079 TI - The end of postoperative antimicrobial prophylaxis? PMID- 22297080 TI - Intraoperative versus extended antimicrobial prophylaxis after gastric cancer surgery: a phase 3, open-label, randomised controlled, non-inferiority trial. AB - BACKGROUND: Although evidence for the efficacy of postoperative antimicrobial prophylaxis is scarce, many patients routinely receive such treatment after major surgeries. We aimed to compare the incidence of surgical-site infections with intraoperative antimicrobial prophylaxis alone versus intraoperative plus postoperative administration. METHODS: We did a prospective, open-label, phase 3, randomised study at seven hospitals in Japan. Patients with gastric cancer that was potentially curable with a distal gastrectomy were randomly assigned (1:1) to receive either intraoperative antimicrobial prophylaxis alone (cefazolin 1 g before the surgical incision and every 3 h as intraoperative supplements) or extended antimicrobial prophylaxis (intraoperative administration plus cefazolin 1 g once after closure and twice daily for 2 postoperative days). Randomisation was stratified using Pocock and Simon's minimisation method for institution and American Society of Anesthesiologists scores, and Mersenne twister was used for random number generation. The primary endpoint was the incidence of surgical-site infections. We assessed non-inferiority of intraoperative therapy with a margin of 5%. Analysis was by intention-to-treat. During hospital stay, infection control personnel assessed patients for infection, and the principal surgeons were required to check for surgical-site infections at outpatient clinics until 30 days after surgery. This study is registered with UMIN-CTR, UMIN000000631. FINDINGS: Between June 2, 2005, and Dec 6, 2007, 355 patients were randomly assigned to receive either intraoperative antimicrobial prophylaxis alone (n=176) or extended antimicrobial prophylaxis (n=179). Eight patients (5%, 95% CI 2-9%) had surgical-site infections in the intraoperative group compared with 16 (9%, 5 14) in the extended group. The relative risk of surgical-site infections with intraoperative antimicrobial prophylaxis was 0.51 (0.22-1.16), which revealed statistically significant non-inferiority (p<0.0001). INTERPRETATION: Elimination of postoperative antimicrobial prophylaxis did not increase the incidence of surgical-site infections after a gastrectomy. Therefore, this treatment is not recommended after gastric cancer surgery. PMID- 22297081 TI - An investigation of admixture in an Australian Aboriginal Y-chromosome STR database. AB - Y-chromosome specific STR profiling is increasingly used in forensic casework. However, the strong geographic clustering of Y haplogroups can lead to large differences in Y-STR haplotype frequencies between different ethnicities, which may have an impact on database composition in admixed populations. Aboriginal people have inhabited Australia for over 40,000 years and until ~300 years ago they lived in almost complete isolation. Since the late 18th century Australia has experienced massive immigration, mainly from Europe, although in recent times from more widespread origins. This colonisation resulted in highly asymmetrical admixture between the immigrants and the indigenes. A State jurisdiction within Australia has created an Aboriginal Y-STR database in which assignment of ethnicity was by self-declaration. This criterion means that some males who identify culturally as members of a particular ethnic group may have a Y haplogroup characteristic of another ethnic group, as a result of admixture in their paternal line. As this may be frequent in Australia, an examination of the extent of genetic admixture within the database was performed. A Y haplogroup predictor program was first used to identify Y haplotypes that could be assigned to a European haplogroup. Of the 757 males (589 unique haplotypes), 445 (58.8%) were identified as European (354 haplotypes). The 312 non-assigned males (235 haplotypes) were then typed, in a hierarchical fashion, with a Y-SNP panel that detected the major Y haplogroups, C-S, as well as the Aboriginal subgroup of C, C4. Among these 96 males were found to have non-Aboriginal haplogroups. In total, ~70% of Y chromosomes in the Aboriginal database could be classed as non indigenous, with only 169 (129 unique haplotypes) or 22% of the total being associated with haplogroups denoting Aboriginal ancestry, C4 and K* or more correctly K(xL,M,N,O,P,Q,R,S). The relative frequencies of these indigenous haplogroups in South Australia (S.A.) were significantly different to those seen in samples from the Northern Territory and Western Australia. In S.A., K* (~60%) has a much higher frequency than C4 (~40%), and the subgroup of C4, C4(DYS390.1del), comprised only 17%. Clearly admixture in the paternal line is at high levels among males who identify themselves as Australian Aboriginals and this knowledge may have implications for the compilation and use of Y-STR databases in frequency estimates. PMID- 22297083 TI - Targeted echocardiography in the neonatal intensive care unit. PMID- 22297084 TI - Three-dimensional mechanical dyssynchrony and myocardial deformation of the left ventricle in patients with tricuspid atresia after Fontan procedure. AB - BACKGROUND: The aim of this study was to test the hypothesis that dyssynchronous contraction of functional single ventricles occurs in Fontan patients and is related to indices of myocardial deformation and global ventricular function. METHODS: Twenty patients with tricuspid atresia (mean age, 23.5 +/- 7.1 years) were studied 17.8 +/- 3.8 years after undergoing the Fontan procedure. Three dimensional echocardiographic data were acquired for determination of left ventricular (LV) volumes and systolic dyssynchrony indices. LV myocardial deformation was determined using speckle-tracking echocardiography. Calibrated integrated backscatter intensity was measured as an index of myocardial fibrosis. The results were compared with those in 20 controls. RESULTS: Compared with controls, patients had significantly greater systolic dyssynchrony indices (6.13 +/- 1.32% vs 4.06 +/- 0.84%, P < .001). The prevalence of LV mechanical dyssynchrony (systolic dyssynchrony index > 5.74%) in patients was 55% (95% confidence interval, 32%-77%). LV global systolic longitudinal, radial, and circumferential strain (P < .001 for all), longitudinal systolic (P < .001) and early diastolic (P < .001) strain rate, and circumferential systolic (P < .001) and early diastolic (P = .009) strain rate were significantly lower in patients than in controls, while the average calibrated integrated backscatter was higher (P < .001). Patients with LV dyssynchrony (n = 11) had lower global LV longitudinal strain (P = .02), reduced LV ejection fractions (P = .002), and higher average calibrated integrated backscatter (P = .03) compared with those without LV dyssynchrony (n = 9). CONCLUSIONS: A high proportion of patients with tricuspid atresia after the Fontan operation exhibit LV mechanical dyssynchrony, which may in part be related to myocardial fibrosis and has implications for myocardial deformation and global ventricular function. PMID- 22297085 TI - Risk of new acute myocardial infarction hospitalization associated with use of oral and parenteral non-steroidal anti-inflammation drugs (NSAIDs): a case crossover study of Taiwan's National Health Insurance claims database and review of current evidence. AB - BACKGROUND: Previous studies have documented the increased cardiovascular risk associated with the use of some nonsteroidal anti-inflammatory drugs (NSAIDs). Despite this, many old NSAIDs are still prescribed worldwide. Most of the studies to date have been focused on specific oral drugs or limited by the number of cases examined. We studied the risk of new acute myocardial infarction (AMI) hospitalization with current use of a variety of oral and parenteral NSAIDs in a nationwide population, and compared our results with existing evidence. METHODS: We conducted a case-crossover study using the Taiwan's National Health Insurance claim database, identifying patients with new AMI hospitalized in 2006. The 1-30 days and 91-120 days prior to the admission were defined as case and matched control period for each patient, respectively. Uses of NSAIDs during the respective periods were compared using conditional logistic regression and adjusted for use of co-medications. RESULTS: 8354 new AMI hospitalization patients fulfilled the study criteria. 14 oral and 3 parenteral NSAIDs were selected based on drug utilization profile among 13.7 million NSAID users. The adjusted odds ratio, aOR (95% confidence interval), for risk of AMI and use of oral and parenteral non-selective NSAIDs were 1.42 (1.29, 1.56) and 3.35 (2.50, 4.47), respectively, and significantly greater for parenteral than oral drugs (p for interaction<0.01). Ketorolac was associated with the highest AMI risk among both of oral and parenteral NSAIDs studied, the aORs were 2.02 (1.00, 4.09) and 4.27 (2.90, 6.29) respectively. Use of oral flurbiprofen, ibuprofen, sulindac, diclofenac, and parenteral ketoprofen were also significantly associated with increased AMI risk. The results of the present study were consistent with the majority of evidence from previous studies. CONCLUSIONS: The collective evidence revealed the tendency of increased AMI risk with current use of some NSAIDs. A higher AMI risk associated with use of parenteral NSAIDs was observed in the present study. Ketorolac had the highest associated risk in both oral and parenteral NSAIDs studied. Though further investigation to confirm the association is warranted, prescribing physicians and the general public should be cautious about the potential risk of AMI when using NSAIDs. PMID- 22297086 TI - Prognostic impact of education level of patients with advanced non-small cell lung cancer enrolled in clinical trials. AB - BACKGROUND: Socioeconomic status can potentially affect prognosis of cancer patients. Our aim was to describe potential differences in demographic and clinical characteristics, treatment, and survival by education level in patients with advanced non-small cell lung cancer (NSCLC) enrolled in clinical trials of first-line treatment. METHODS: Individual data of Italian patients with advanced NSCLC (stage IV, or IIIB with supraclavicular nodes or malignant pleural effusion), ECOG performance status (PS) 0-2, enrolled in four phase III randomized trials conducted between 1996 and 2005 were pooled. Information about education was available for 1680 of 1709 patients (98.3%). Patients were divided in two groups according to education level: high (patients with at least high school diploma) or low (those with less than high school diploma). Survival analyses were stratified by treatment arm within trial. RESULTS: There were 312 (19%) and 1368 (81%) patients with high and low education, respectively. Education level was significantly different among birth cohorts, with a time trend toward higher education level. Patients with high education were significantly younger (median age 65 vs. 70), were less frequently unfit at diagnosis (ECOG PS2 5% vs. 16%), and their tumor type was more frequently adenocarcinoma (47% vs. 37%). Number of treatment cycles received was not significantly different between education groups. Median survival was 9.4 and 7.6 months in high and low education, respectively (p=0.012). At multivariable analysis, female sex, better PS and high education level (Hazard Ratio 0.85, 95%CI 0.73-0.99, p=0.03) were independently associated with longer survival. CONCLUSIONS: In Italian patients enrolled in four randomized trials of first-line chemotherapy for advanced NSCLC, high education was significantly more frequent among younger patients, and was associated with lower proportion of PS2 patients. Education level did not significantly affect number of chemotherapy cycles received. Overall survival was longer in patients with high education, after adjustment for PS and other prognostic factors. The exact underlying mechanisms of the independent prognostic role of education level are substantially unknown, but lead-time bias (anticipation in diagnosis and time to inclusion in the trial), differences in adherence to care outside the trial procedures, differences in comorbidities and life-style factors may all contribute. PMID- 22297087 TI - Deformation behavior of the iliotibial tract under different states of fixation. AB - BACKGROUND AND OBJECTIVE: The iliotibial tract (tract) is an important structure for the biomechanics of both the hip and knee joint. While a detailed characterization of its mechanical properties might help to better understand its specific role in the load transfer from the pelvis to femur and tibia, determination of those properties is complicated by its particular structure of thin fibers in the fresh state. Moreover, although the tracts mechanical properties are often derived from cadaveric material chemically fixed with either ethanol or formaldehyde, the influence of such fixation methods remains to be elucidated. Aim of this study was to determine Young's modulus (tensile modulus, YM) of the tract. We hypothesized that either ethanol or formaldehyde fixation would significantly increase the YM compared to the tracts condition in a fresh state. MATERIAL AND METHODS: 13 specimens of tract were gained from donators. The ends of the probes were plastinated with resin creating a sharp interface between the clamp and the probe to prevent material slippage. The specimens were measured in their fresh state, under ethanol- and formaldehyde-fixed conditions and re measured after rinsing with tap water. RESULTS: The YM of the fresh probes averaged 397.3N/mm(2) with a standard deviation (SD) of 151.5N/mm(2). The YM of the ethanol-fixed specimens was significantly higher (673.2N/mm(2), SD 328.5N/mm(2), p<0.05). After rinsing with tap water, the YM decreased to 95% of the fresh condition value (377.4N/mm(2), SD 144.5N/mm(2), non-significant change from fresh). After formaldehyde fixation, the YM reached 490.3N/mm(2) (SD 143.0N/mm(2), p<0.05). When the formaldehyde-fixed specimens were rinsed, the YM was 114% of the value of the fresh condition (452.6N/mm(2), SD 115.1N/mm(2), non significant change from fresh). CONCLUSIONS: This study found a significant influence of the chemical fixation method on the YM of the IT tract. If such fixation is required, our results suggest using a treatment with ethanol and subsequent rinsing that results in minimal changes to the tracts YM. Furthermore, plastination of the ends of the specimens could be crucial to allow in vitro determination of valid YM of ligaments data that can then be integrated with confidence in further finite element analyses. PMID- 22297088 TI - Nonlinear analysis of actigraphic signals for the assessment of the attention deficit/hyperactivity disorder (ADHD). AB - Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder in children and adolescents; however, its etiology is still unknown, which hinders the existence of reliable, fast and inexpensive standard diagnostic methods. In this paper, we propose a novel methodology for automatic diagnosis of the combined type of ADHD based on nonlinear signal processing of 24h-long actigraphic registries. Since it relies on actigraphy measurements, it constitutes an inexpensive and non-invasive objective diagnostic method. Our results on real data reach 96.77% sensitivity and 84.38% specificity by means of multidimensional classifiers driven by combined features from different time intervals. Our analysis also reveals that, if features from a single time interval are used, the whole 24-h interval is the only one that yields classification figures with practical diagnostic capabilities. Overall, our figures overcome those obtained by actigraphy-based methods reported and are comparable with others based on more expensive (and not so convenient) adquisition methods. PMID- 22297089 TI - Carbon nanohorn-based nanofluids: characterization of the spectral scattering albedo. AB - The full characterization of the optical properties of nanofluids consisting of single-wall carbon nanohorns of different morphologies in aqueous suspensions is carried out using a novel spectrophotometric technique. Information on the nanofluid scattering and absorption spectral characteristics is obtained by analyzing the data within the single scattering theory and validating the method by comparison with previous monochromatic measurements performed with a different technique. The high absorption coefficient measured joint to the very low scattering albedo opens promising application perspectives for single-wall carbon nanohorn-based fluid or solid suspensions. The proposed approximate approach can be extended also to other low-scattering turbid media.PACS: 78.35.+c Brillouin and Rayleigh scattering, other light scattering; 78.40.Ri absorption and reflection spectra, fullerenes and related materials; 81.05.U- carbon/carbon based materials; 78.67.Bf optical properties of low-dimensional, mesoscopic, and nanoscale materials and structures, nanocrystals, nanoparticles, and nanoclusters. PMID- 22297090 TI - Study of fluorescence quenching of Barley alpha-amylase. AB - The fluorescence quenching of Barley alpha-amylase by acrylamide and succinimide has been studied in water using steady-state and time-resolved fluorescence techniques. The steady-state fluorescence quenching technique has been performed in three different pHs (i.e., 6, 7 and 8) of water. Ground state and excited state binding constants (K(g) &K(e)) have been calculated. From the calculated binding constants (K(g) &K(e)) the free energy changes for the ground (DeltaG(g)) and excited (DeltaG(e)) states have been calculated and are presented in tables. UV and FTIR spectra have also been recorded to prove the binding of Barley alpha amylase with acrylamide and succinimide. PMID- 22297091 TI - The infrared fundamental intensities of some cyanopolyynes. AB - Some cyanopolyynes, HC(n)N (n=1, 3, ..., 17), are investigated by means of calculations at the MP2/cc-pVTZ and CCSD/cc-pVDZ levels. Although the MP2/cc-pVTZ results for geometries and molecular dipole moments are encouraging, the CCSD/cc pVDZ level was superior for the study of infrared fundamental intensities. The main bands are also analyzed with a charge-charge flux-dipole flux (CCFDF) partition model based on quantities given by the Quantum Theory of Atoms in Molecules (QTAIM). The intensity of vibrations corresponding to the stretching of CH bonds (3471-3473 cm(-1)) increases in line with the number of carbon atoms (from 61 to 146 km mol(-1) between HCN and HC(13)N). This increase is due to the charge flux contribution while the other contributions remain roughly unaltered except for HCN. Moreover, the hydrogen atom loses an almost constant amount of electronic charge during the CH bond enlargement and a small fraction of this charge spreads to atoms farther and farther away from hydrogen as the molecule size increases. The band associated with the doubly degenerate CH bending vibrations (643-732 cm(-1)) presents approximately the same intensity in all the studied cyanopolyynes (from 67 to 76 km mol(-1)). The CCFDF/QTAIM contributions are also nearly the same for these bending modes in HC(5)N and larger systems. The intensity of the mode mostly identified as CN stretching (around 2378-2399 cm(-1) except for HCN) increases from HCN up to HC(7)N (from 0.3 to 83 km mol( 1)) and nearly stabilizes around 80-90 km mol(-1) for larger systems. The CCFDF/QTAIM contributions for this mode also change significantly up to HC(7)N and remain almost constant in larger systems. We also observed the appearing of a very relevant band between 2283 and 2342 cm(-1). This mode is mainly associated with the symmetric stretching of CC triple bonds near the molecule center and exhibits large charge fluxes while the other contributions are almost negligible in the largest cyanopolyynes. The two vibrational bands associated with the smallest frequencies are also studied and extrapolation equations are suggested to predict their positions in larger cyanopolyynes. PMID- 22297092 TI - FDA risk assessment of seafood contamination after the BP oil spill. PMID- 22297093 TI - Web-based recruiting for health research using a social networking site: an exploratory study. AB - BACKGROUND: Recruitment of young people for health research by traditional methods has become more expensive and challenging over recent decades. The Internet presents an opportunity for innovative recruitment modalities. OBJECTIVE: To assess the feasibility of recruiting young females using targeted advertising on the social networking site Facebook. METHODS: We placed an advertisement on Facebook from May to September 2010, inviting 16- to 25-year-old females from Victoria, Australia, to participate in a health study. Those who clicked on the advertisement were redirected to the study website and were able to express interest by submitting their contact details online. They were contacted by a researcher who assessed eligibility and invited them to complete a health-related survey, which they could do confidentially and securely either at the study site or remotely online. RESULTS: A total of 551 females responded to the advertisement, of whom 426 agreed to participate, with 278 completing the survey (139 at the study site and 139 remotely). Respondents' age distribution was representative of the target population, while 18- to 25-year-olds were more likely to be enrolled in the study and complete the survey than 16- to 17-year olds (prevalence ratio=1.37, 95% confidence interval 1.05-1.78, P=.02). The broad geographic distribution (major city, inner regional, and outer regional/remote) and socioeconomic profile of participants matched the target population. Predictors of participation were older age, higher education level, and higher body mass index. Average cost in advertising fees per compliant participant was US $20, making this highly cost effective. CONCLUSIONS: Results demonstrate the potential of using modern information and communication technologies to engage young women in health research and penetrate into nonurban communities. The success of this method has implications for future medical and population research in this and other demographics. PMID- 22297094 TI - Collective motion of microspheres in suspensions observed by phase-mode dynamic ultrasound scattering technique. AB - Compared with a nano-sized particle, dynamics of a micron-sized particle in a liquid is often associated with sedimentation (or floating) due to its relatively large mass. The motion of more than two particles is dominated by the hydrodynamic interactions, which are known to persist over a fairly long range, e.g., several millimeters, in suspensions. The particle size may be obtained from the dynamic ultrasound scattering (DSS) technique by the analysis of velocity fluctuations, whose origin is believed to take root in the particle-number fluctuations among temporally formed domains involving collective motion of particles with a certain cut-off length. In this study, such collective particle motion in highly turbid solutions was visualized by means of the phase-mode DSS technique with a single element transducer. Quantitative agreement between the velocity fluctuations obtained by the phase- and conventional amplitude-mode analyses was confirmed, followed by examination of the concentration and the particle size dependences on the dynamic structures induced by the long-ranged interactions. It was found that the phase mode-DSS was a promising method to evaluate the time-dependent structures of the micro-particles in highly turbid suspensions. PMID- 22297095 TI - The major secreted protein Msp1/p75 is O-glycosylated in Lactobacillus rhamnosus GG. AB - BACKGROUND: Although the occurrence, biosynthesis and possible functions of glycoproteins are increasingly documented for pathogens, glycoproteins are not yet widely described in probiotic bacteria. Nevertheless, knowledge of protein glycosylation holds important potential for better understanding specific glycan mediated interactions of probiotics and for glycoengineering in food-grade microbes. RESULTS: Here, we provide evidence that the major secreted protein Msp1/p75 of the probiotic Lactobacillus rhamnosus GG is glycosylated. Msp1 was shown to stain positive with periodic-acid Schiff staining, to be susceptible to chemical deglycosylation, and to bind with the mannose-specific Concanavalin A (ConA) lectin. Recombinant expression in Escherichia coli resulted in a significant reduction in molecular mass, loss of ConA reactivity and increased sensitivity towards pronase E and proteinase K. Mass spectrometry showed that Msp1 is O-glycosylated and identified a glycopeptide TVETPSSA (amino acids 101 108) bearing hexoses presumably linked to the serine residues. Interestingly, these serine residues are not present in the homologous protein of several Lactobacillus casei strains tested, which also did not bind to ConA. The role of the glycan substitutions in known functions of Msp1 was also investigated. Glycosylation did not seem to impact significantly on the peptidoglycan hydrolase activity of Msp1. In addition, the glycan chain appeared not to be required for the activation of Akt signaling in intestinal epithelial cells by Msp1. On the other hand, examination of different cell extracts showed that Msp1 is a glycosylated protein in the supernatant, but not in the cell wall and cytosol fraction, suggesting a link between glycosylation and secretion of this protein. CONCLUSIONS: In this study we have provided the first evidence of protein O glycosylation in the probiotic L rhamnosus GG. The major secreted protein Msp1 is glycosylated with ConA reactive sugars at the serine residues at 106 and 107. Glycosylation is not required for the peptidoglycan hydrolase activity of Msp1 nor for Akt activation capacity in epithelial cells, but appears to be important for its stability and protection against proteases. PMID- 22297096 TI - Quantitation of glucose uptake in tumors by dynamic FDG-PET has less glucose bias and lower variability when adjusted for partial saturation of glucose transport. AB - BACKGROUND: A retrospective analysis of estimates of tumor glucose uptake from 1,192 dynamic 2-deoxy-2-(18F)fluoro-D-glucose-positron-emission tomography [FDG PET] scans showed strong correlations between blood glucose and both the uptake rate constant [Ki] and the metabolic rate of glucose [MRGluc], hindering the interpretation of PET scans acquired under conditions of altered blood glucose. We sought a method to reduce this glucose bias without increasing the between subject or test-retest variability and did this by considering that tissue glucose transport is a saturable yet unsaturated process best described as a nonlinear function of glucose levels. METHODS: Patlak-Gjedde analysis was used to compute Ki from 30-min dynamic PET scans in tumor-bearing mice. MRGluc was calculated by factoring in the blood glucose level and a lumped constant equal to unity. Alternatively, we assumed that glucose consumption is saturable according to Michaelis-Menten kinetics and estimated a hypothetical maximum rate of glucose consumption [MRGlucMAX] by multiplying Ki and (KM + [glucose]), where KM is a half-saturation Michaelis constant for glucose uptake. Results were computed for 112 separate studies of 8 to 12 scans each; test-retest statistics were measured in a suitable subset of 201 mice. RESULTS: A KM value of 130 mg/dL was determined from the data based on minimizing the average correlation between blood glucose and the uptake metric. Using MRGlucMAX resulted in the following benefits compared to using MRGluc: (1) the median correlation with blood glucose was practically zero, and yet (2) the test-retest coefficient of variation [COV] was reduced by 13.4%, and (3) the between-animal COVs were reduced by15.5%. In statistically equivalent terms, achieving the same reduction in between-animal COV while using the traditional MRGluc would require a 40% increase in sample size. CONCLUSIONS: MRGluc appeared to overcorrect tumor FDG data for changing glucose levels. Applying partial saturation correction using MRGlucMAX offered reduced bias, reduced variability, and potentially increased statistical power. We recommend further investigation of MRGlucMAX in quantitative studies of tumor FDG uptake. PMID- 22297097 TI - Case report of Ganser syndrome in a 14-year-old girl: another face of depressive disorder? AB - The Ganser syndrome is rare in children and in adolescents. A case of the Ganser syndrome in a 14-year-old girl, with three of the four essential features, is presented. After rapid resolution in two weeks, Ganser symptoms reappear seven months later accompanied, this second time, by previous depressive symptoms. This report raises the possibility of the Ganser syndrome as a manifestation of a depressive disorder in adolescence. PMID- 22297098 TI - Q fever: new insights, still many queries. PMID- 22297099 TI - Applicability of evidence-based practice in public health: risk assessment on Q fever under an ongoing outbreak. AB - With reference to the Q fever outbreak in the Netherlands in 2009-10, we tested if an evidence-based approach, comparable to the methodology used in clinical medicine, was appropriate for giving public health advice under time constrains. According to the principles of evidence-based methodologies, articles were retrieved from bibliographic databases and categorised by type and size, outcome, strengths and limitations. The risk assessment was conducted in two months and involved six staff members. We retrieved and read 559 abstracts and selected approximately 150 full text articles. The most striking finding was the lack of sound scientific evidence behind standard treatment regimes for Q fever in pregnancy. Difficulties in applying existing evidence rating systems and in expressing uncertainties were identified as problems during the process. By systematically assessing the evidence on several questions about Q fever, we were able to draw new conclusions and specify earlier statements. We found it difficult to grade the mostly observational studies with the known evidence-based grading systems. There is need to develop new methods for grading evidence from different sources in the field of public health. We conclude that an evidence based approach is feasible for providing a risk assessment within two to three months. PMID- 22297100 TI - Relation between Q fever notifications and Coxiella burnetii infections during the 2009 outbreak in The Netherlands. AB - Large outbreaks of Q fever in the Netherlands from 2007 to 2009 were monitored using notification data of acute clinical Q fever. However, the notification system provides no information on infections that remain subclinical or for which no medical attention is sought. The present study was carried out immediately after the peak of the 2009 outbreak to estimate the ratio between Coxiella burnetii infections and Q fever notifications. In 23 postcode areas in the high incidence area, notification rates were compared with seroconversion rates in blood donors from whom serial samples were available. This resulted in a ratio of one Q fever notification to 12.6 incident infections of C. burnetii. This ratio is time and place specific and is based on a small number of seroconversions, but is the best available factor for estimating the total number of infections. In addition, as subclinical C. burnetii infection may lead to chronic Q fever, the ratio can be used to estimate the expected number of chronic Q fever patients in the coming years and as input for cost-benefit analyses of screening options. PMID- 22297101 TI - Shifting priorities in the aftermath of a Q fever epidemic in 2007 to 2009 in The Netherlands: from acute to chronic infection. AB - From 2007 to 2009, the Netherlands faced large seasonal outbreaks of Q fever, in which infected dairy goat farms were identified as the primary sources. Veterinary measures including vaccination of goats and sheep and culling of pregnant animals on infected farms seem to have brought the Q fever problem under control. However, the epidemic is expected to result in more cases of chronic Q fever among risk groups in the coming years. In the most affected area, in the south of the country, more than 12% of the population now have antibodies against Coxiella burnetii. Questions remain about the follow-up of acute Q fever patients, screening of groups at risk for chronic Q fever, screening of donors of blood and tissue, and human vaccination. There is a considerable ongoing research effort as well as enhanced veterinary and human surveillance. PMID- 22297103 TI - Follow Eurosurveillance on Twitter. PMID- 22297102 TI - Screening for Coxiella burnetii infection during pregnancy: pros and cons according to the Wilson and Jungner criteria. AB - In Europe the incidence of human Q fever has dramatically increased over the previous years. Untreated infections with Coxiella burnetii, the causal agent of Q fever, have been associated with both obstetric and maternal complications. The majority of pregnant women with a C. burnetii infection remain asymptomatic, hence screening could be of value to prevent unwanted outcomes in this high-risk group. We applied the updated Wilson and Jungner criteria to review the evidence for routine screening for C. burnetii infection during pregnancy. Since much uncertainty remains about the incidence, clinical consequences, diagnostics and treatment of C. burnetii infection during pregnancy, routine screening for C. burnetii infection during pregnancy should not be recommended. Rigorous studies to assess the effectiveness of C. burnetii screening are warranted. PMID- 22297104 TI - Pulsed radiofrequency electromagnetic field therapy: a potential novel treatment of plantar fasciitis. AB - Plantar fasciitis is a common cause of heel pain, and although treatments are usually conservative, they can take up to 2 years to achieve resolution. A double blind, multicenter, randomized, placebo-controlled study was used to evaluate a small, wearable, extended-use pulsed radiofrequency electromagnetic field (PRFE) device as a treatment of plantar fasciitis. A total of 70 subjects diagnosed with plantar fasciitis were enrolled in the present study. The subjects were randomly assigned a placebo or active PRFE device. The subjects were instructed to wear the PRFE device overnight, record their morning and evening pain using a 0- to 10 point visual analog scale (VAS), and log any medication use. The primary outcome measure for the present study was morning pain, a hallmark of plantar fasciitis. The study group using the active PRFE device showed progressive decline in morning pain. The day 7 AM-VAS score was 40% lower than the day 1 AM-VAS score. The control group, in comparison, showed a 7% decline. A significantly different decline was demonstrated between the 2 groups (p = .03). The PM-VAS scores declined by 30% in the study group and 19% in the control group, although the difference was not significant. Medication use in the study group also showed a trend downward, but the use in the control group remained consistent with the day 1 levels. PRFE therapy worn on a nightly basis appears to offer a simple, drug free, noninvasive therapy to reduce the pain associated with plantar fasciitis. PMID- 22297105 TI - An unusual case of fibular (postaxial) polydactyly: extrametatarsal head with fused duplication of the proximal phalanx. AB - Polydactyly of the foot is a congenital anomaly characterized by the appearance of all or part of 1 or more additional rays. A number of morphologically and anatomically based classifications exist. We present an unusual case of fibular (postaxial) polydactyly characterized by an extrametatarsal head with fused duplication of the proximal phalanx. We describe the method of surgical correction and emphasize the need for careful preoperative planning to achieve a good functional and cosmetic outcome. PMID- 22297106 TI - Chondroblastoma in a metatarsal treated with autogenous fibular graft: a case report. AB - Chondroblastoma is a relatively rare tumor that mimics giant cell tumor and displays a predilection for long bones. In the present report, we describe the case of a benign chondroblastoma localized to the second metatarsal in a 20-year old male who presented with a 2-year history of painless left foot swelling. Treatment of the tumor involved excision of the second metatarsal with use of an autologous structural fibular bone graft to stabilize the metatarsus and second toe. After 27 months of follow-up, the patient was ambulating well in regular shoes, with no clinical or radiographic evidence of tumor recurrence. PMID- 22297107 TI - Anatomic description of the distal tibia: implications for internal fixation. AB - Fracture fixation using minimally invasive plating techniques around the distal tibia are well described, although there are a number of potential hazards and complications. Our study provides an anatomical description of the distal tibia and its relations to surrounding structures. Twenty magnetic resonance imaging scans of the distal tibia were analyzed in the coronal, sagittal, and axial planes. Measurements were taken by 2 observers on 2 occasions of the distance of anterior structures from the tibial cortex as well as dimensional parameters. The mean dimensions of the distal tibia at the level of the plafond were 39 mm medial lateral and 36 mm anteroposterior. The anterior neurovascular bundle was found to be a mean of 3 mm from the anterior tibial cortex with the anterior tendinous structures located <6 mm. The intraclass correlation coefficient for the first observer was 0.8 and for the second observer was 0.78 with an interclass correlation coefficient of 0.8. This demonstrated excellent interobserver and intraobserver reliability. This study presents the first magnetic resonance imaging-based anatomical description of the distal tibia. It showed that key anatomical structures are in very close proximity to the distal tibia, and this is important to consider when treating fractures in this region with internal fixation. PMID- 22297108 TI - Endogenously determined restriction of food intake overcomes excitation contraction uncoupling in JP45KO mice with aging. AB - The decline in muscular strength with age is disproportionate to the loss in total muscle mass that causes it. Knocking out JP45, an integral protein of the junctional face membrane of the skeletal muscle sarcoplasmic reticulum (SR), results in decreased expression of the voltage-gated Ca(2+) channel, Ca(v)1.1; excitation-contraction uncoupling (ECU); and loss of muscle force (Delbono et al., 2007). Here, we show that Ca(v)1.1 expression, charge movement, SR Ca(2+) release, in vitro contractile force, and sustained forced running remain stable in male JP45KO mice at 12 and 18 months. They also exhibit the level of ECU reported for 3-4-month mice (Delbono et al., 2007). No further decline at later ages was recorded. Preserved ECC was not related to increased expression of any protein that directly or indirectly interacts with JP45 at the triad junction. However, maintained muscle force and physical performance were associated with ablation of JP45 expression in the brain, spontaneous and significantly diminished food intake and less tendency toward obesity when exposed to a high fat diet compared to WT. We propose that (1) endogenously generated restriction in food intake overcomes the deleterious effects of JP45 ablation on ECC and skeletal muscle force mainly through downregulation of neuropeptide-Y expression in the hypothalamic arcuate nucleus; and (2) the JP45KO mouse constitutes an invaluable model to examine the mechanisms controlling food intake as well as skeletal muscle function with aging. PMID- 22297109 TI - Development of small-molecule probes that selectively kill cells induced to express mutant RAS. AB - Synthetic lethal screening is a chemical biology approach to identify small molecules that selectively kill oncogene-expressing cell lines with the goal of identifying pathways that provide specific targets against cancer cells. We performed a high-throughput screen of 303,282 compounds from the National Institutes of Health-Molecular Libraries Small Molecule Repository (NIH-MLSMR) against immortalized BJ fibroblasts expressing HRAS(G12V) followed by a counterscreen of lethal compounds in a series of isogenic cells lacking the HRAS(G12V) oncogene. This effort led to the identification of two novel molecular probes (PubChem CID 3689413, ML162 and CID 49766530, ML210) with nanomolar potencies and 4-23-fold selectivities, which can potentially be used for identifying oncogene-specific pathways and targets in cancer cells. PMID- 22297110 TI - [11C]GSK2126458 and [18F]GSK2126458, the first radiosynthesis of new potential PET agents for imaging of PI3K and mTOR in cancers. AB - GSK2126458 is a highly potent inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) with low picomolar to subnanomolar activity. [(11)C]GSK2126458 and [(18)F]GSK2126458, new potential PET agents for imaging of PI3K and mTOR in cancer, were first designed and synthesized in 40-50% and 20-30% decay corrected radiochemical yield, and 370-740 and 37-222GBq/MUmol specific activity at end of bombardment (EOB), respectively. PMID- 22297111 TI - Novel morpholine ketone analogs as potent histamine H3 receptor inverse agonists with wake activity. AB - Structure-activity relationship on a novel ketone class of H(3)R antagonists/inverse agonists is disclosed. Compound 4 showed excellent target potency, selectivity and brain penetration. Evaluation of antagonist 4 in the rat EEG/EMG model demonstrated robust wake activity thereby establishing preclinical proof of concept. PMID- 22297112 TI - Substitution of Gly with Ala enhanced the melanoma uptake of technetium-99m labeled Arg-Ala-Asp-conjugated alpha-melanocyte stimulating hormone peptide. AB - The purpose of this study was to determine the melanoma targeting property of (99m)Tc-RAD-Lys-(Arg(11))CCMSH in B16/F1 melanoma-bearing C57 mice and compare with (99m)Tc-RGD-Lys-(Arg(11))CCMSH we previously reported. (99m)Tc-RAD-Lys (Arg(11))CCMSH exhibited rapid and high tumor uptake (19.91+/-4.02% ID/g at 2h post-injection) in B16/F1 melanoma-bearing C57 mice. The tumor uptake of (99m)Tc RAD-Lys-(Arg(11))CCMSH was 1.51, 1.34 and 1.43 times the tumor uptake of (99m)Tc RGD-Lys-(Arg(11))CCMSH at 0.5, 2 and 4h post-injection, respectively. Flank B16/F1 melanoma lesions were clearly imaged at 2h post-injection using (99m)Tc RAD-Lys-(Arg(11))CCMSH as an imaging probe. The substitution of Gly with Ala significantly enhanced the melanoma uptake of (99m)Tc-RAD-Lys-(Arg(11))CCMSH compared to (99m)Tc-RGD-Lys-(Arg(11))CCMSH in B16/F1 melanoma-bearing C57 mice, providing a new insight into the design of alpha-MSH peptides for melanoma targeting. PMID- 22297113 TI - A benzothiazole alkyne fluorescent sensor for Cu detection in living cell. AB - A new type of alkyne dye, 6-dimethylaminobenzothiazole alkyne (1), was developed for Cu sensing in biological system. Dye (1) offered excellent selective over a panel of ions, only Cu(I) could change the fluorescence of dye (I) by forming copper acetylide between the terminal alkyne and Cu(I). Its potential of detecting Cu in biological system was demonstrated in cell culture. PMID- 22297114 TI - Dual beta2-adrenoceptor agonists-PDE4 inhibitors for the treatment of asthma and COPD. AB - We designed and synthesized a novel class of dual pharmacology bronchodilators targeting both beta(2)-adrenoceptor and PDE4 by applying a multivalent approach. The most potent dual pharmacology molecule, compound 29, possessed good inhibitory activity on PDE4B2 (IC(50)=0.278 MUM, which was more potent than phthalazinone, IC(50)=0.520 MUM) and possessed excellent relaxant effects on tracheal rings precontracted by histamine (pEC(50)=9.3). PMID- 22297115 TI - Inhibitors of acetyltransferase domain of N-acetylglucosamine-1-phosphate uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU). Part 1: Hit to lead evaluation of a novel arylsulfonamide series. AB - A novel arylsulfonamide-containing series of compounds represented by 1, discovered by highthroughput screening, inhibit the acetyltransferase domain of N acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate acetyltransferase (GlmU). X-ray structure determination confirmed that inhibitor binds at the site occupied by acetyl-CoA, indicating that series is competitive with this substrate. This letter documents our early hit-to-lead evaluation of the chemical series and some of the findings that led to improvement in in-vitro potency against Gram-negative and Gram-positive bacterial isozymes, exemplified by compound 40. PMID- 22297116 TI - Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves. AB - BACKGROUND: The results of Randomized Controlled Trials (RCTs) on time-to-event outcomes that are usually reported are median time to events and Cox Hazard Ratio. These do not constitute the sufficient statistics required for meta analysis or cost-effectiveness analysis, and their use in secondary analyses requires strong assumptions that may not have been adequately tested. In order to enhance the quality of secondary data analyses, we propose a method which derives from the published Kaplan Meier survival curves a close approximation to the original individual patient time-to-event data from which they were generated. METHODS: We develop an algorithm that maps from digitised curves back to KM data by finding numerical solutions to the inverted KM equations, using where available information on number of events and numbers at risk. The reproducibility and accuracy of survival probabilities, median survival times and hazard ratios based on reconstructed KM data was assessed by comparing published statistics (survival probabilities, medians and hazard ratios) with statistics based on repeated reconstructions by multiple observers. RESULTS: The validation exercise established there was no material systematic error and that there was a high degree of reproducibility for all statistics. Accuracy was excellent for survival probabilities and medians, for hazard ratios reasonable accuracy can only be obtained if at least numbers at risk or total number of events are reported. CONCLUSION: The algorithm is a reliable tool for meta-analysis and cost effectiveness analyses of RCTs reporting time-to-event data. It is recommended that all RCTs should report information on numbers at risk and total number of events alongside KM curves. PMID- 22297117 TI - Clinical practice guidelines and patient decision aids. An inevitable relationship. AB - As health professionals and patients are moving toward shared models of decision making, there is a growing need for integrated decision support tools that facilitate uptake of best evidence in routine clinical practice in a patient centered manner. This article charts the landscape of clinical practice guidelines (CPGs) and patient decision aids. Decision support tools for medical practice can be mapped on two dimensions. (1) The target user and his or her level of decision making; either for groups of patients or for an individual patient and (2) the level of uncertainty: either supporting more directive decision making (behavior support) in the case of strong recommendations with a single best option or supporting dialog (deliberation support) on the pros and cons of different options in the case of conditional (or weak) recommendations. We conclude that it is important to establish closer links between CPGs and patient decision aids, through collaborative development of both. Such collaboration will encourage the design of decision support tools for professionals and patients who share the same evidence and the aim to increase the quality of decision making between doctor and patient. This could facilitate the implementation of CPGs and shared decision making in clinical practice. PMID- 22297118 TI - Predicting the clinical behaviour of cavernous malformations. PMID- 22297120 TI - Preschoolers' social dominance, moral cognition, and moral behavior: an evolutionary perspective. AB - Various aspects of moral functioning, aggression, and positive peer regard were assessed in 153 preschool children. Our hypotheses were inspired by an evolutionary approach to morality that construes moral norms as tools of the social elite. Accordingly, children were also rated for social dominance and strategies for its attainment. We predicted that aspects of moral functioning would be only loosely related to each other and that moral cognitions about rules (unlike emotion attributions and moral internalization) would demonstrate patterns suggestive of instrumentality. Results showed that cognitions about moral rules and internalized conscience were unrelated and that sociomoral behavior was more strongly related to the latter than to the former. In addition, promoting group norms (Selective Moral Engagement) positively predicted social dominance, whereas internalized conscience negatively predicted social dominance. Children who controlled resources via both prosocial and coercive means (i.e., bistrategic) showed enhanced moral cognitions about rules (despite high levels of aggression) but had deficits in emotional aspects of moral functioning in the eyes of teachers. Patterns of Selective Moral Engagement invite comparisons to tattling and impression management. The findings are contrasted with alternative hypotheses that are advanced from traditional yet prevailing approaches. PMID- 22297121 TI - Rapid naming speed components and reading development in a consistent orthography. AB - We examined how rapid automatized naming (RAN) components-articulation time and pause time-predict word and text reading fluency in a consistent orthography (Greek). In total, 68 children were followed from Grade 2 to Grade 6 and were assessed three times on RAN (Digits and Objects), phonological awareness, orthographic processing, speed of processing, and reading fluency. Both RAN components were strongly related to reading fluency and, with few exceptions, accounted for unique variance over and above the contribution of speed of processing, phonological awareness, and orthographic processing. The amount of predictive variance shared between the components and the cognitive processing skills varied across time. The implications of these findings for the RAN-reading relationship are discussed. PMID- 22297122 TI - Road mapping ATLAS ACS 2: are we there yet? PMID- 22297123 TI - Can cardiac resynchronization therapy cause harm? PMID- 22297119 TI - Untreated clinical course of cerebral cavernous malformations: a prospective, population-based cohort study. AB - BACKGROUND: Cerebral cavernous malformations (CCMs) are prone to bleeding but the risk of intracranial haemorrhage and focal neurological deficits, and the factors that might predict their occurrence, are unclear. We aimed to quantify these risks and investigate whether they are affected by sex and CCM location. METHODS: We undertook a population-based study using multiple overlapping sources of case ascertainment (including a Scotland-wide collaboration of neurologists, neurosurgeons, stroke physicians, radiologists, and pathologists, as well as searches of registers of hospital discharges and death certificates) to identify definite CCM diagnoses first made in Scottish residents between 1999 and 2003, which study neuroradiologists independently validated. We used multiple sources of prospective follow-up both to identify outcome events (which were assessed by use of brain imaging, by investigators masked to potential predictive factors) and to assess adults' dependence. The primary outcome was a composite of intracranial haemorrhage or focal neurological deficits (not including epileptic seizure) that were definitely or possibly related to CCM. FINDINGS: 139 adults had at least one definite CCM and 134 were alive at initial presentation. During 1177 person-years of follow-up (completeness 97%), for intracranial haemorrhage alone the 5-year risk of a first haemorrhage was lower than the risk of recurrent haemorrhage (2.4%, 95% CI 0.0-5.7 vs 29.5%, 4.1-55.0; p<0.0001). For the primary outcome, the 5-year risk of a first event was lower than the risk of recurrence (9.3%, 3.1-15.4 vs 42.4%, 26.8-58.0; p<0.0001). The annual risk of recurrence of the primary outcome declined from 19.8% (95% CI 6.1-33.4) in year 1 to 5.0% (0.0 14.8) in year 5 and was higher for women than men (p=0.01) but not for adults with brainstem CCMs versus CCMs in other locations (p=0.17). INTERPRETATION: The risk of recurrent intracranial haemorrhage or focal neurological deficit from a CCM is greater than the risk of a first event, is greater for women than for men, and declines over 5 years. This information can be used in clinical practice, but further work is needed to quantify risks precisely in the long term and to understand why women are at greater risk of recurrence than men. FUNDING: UK Medical Research Council, Chief Scientist Office of the Scottish Government, and UK Stroke Association. PMID- 22297124 TI - The effect of intravenous ferric carboxymaltose on health-related quality of life in patients with chronic heart failure and iron deficiency: a subanalysis of the FAIR-HF study. AB - AIMS: Patients with chronic heart failure (CHF) show impaired health-related quality of life (HRQoL), an important target for therapeutic intervention. Impaired iron homeostasis may be one mechanism underlying the poor physical condition of CHF patients. This detailed subanalysis of the previously published FAIR-HF study evaluated baseline HRQoL in iron-deficient patients with CHF and the effect of intravenous ferric carboxymaltose (FCM) on HRQoL. METHODS AND RESULTS: FAIR-HF randomized 459 patients with reduced left ventricular ejection fraction and iron deficiency, with or without anaemia, to FCM or placebo (2:1). Health-related quality of life was assessed at baseline and after 4, 12, and 24 weeks of therapy using the generic EQ-5D questionnaire and disease-specific Kansas City cardiomyopathy questionnaire (KCCQ). Baseline mean visual analogue scale (VAS) score was 54.3 +/- 16.4 and KCCQ overall summary score was 52.4 +/- 18.8. Ferric carboxymaltose significantly improved VAS and KCCQ (mean differences from baseline in KCCQ overall, clinical and total symptom scores, P< 0.001 vs. placebo) at all time points. At week 24, significant improvement vs. placebo was observed in four of the five EQ-5D dimensions: mobility (P= 0.004), self-care (P< 0.001), pain/discomfort (P= 0.006), anxiety/depression (P= 0.012), and usual activity (P= 0.035). Ferric carboxymaltose improved all KCCQ domain mean scores from Week 4 onward (P<= 0.05), except for self-efficacy and social limitation. Effects were present in both anaemic and non-anaemic patients. CONCLUSIONS: HRQoL is impaired in iron-deficient patients with CHF. Intravenous FCM significantly improved HRQoL after 4 weeks, and throughout the remaining study period. The positive effects of FCM were independent of anaemia status. PMID- 22297125 TI - Parkinson's disease and risk of hip fracture: an 8-year follow-up study in Taiwan. AB - BACKGROUND: Patients with Parkinson's disease (PD) are subject to posture instability and falling. However, PD was not included as one of the risk factors in commonly used fracture risk calculation tools and the fracture rate in patients with PD was rarely reported. The aim of this study was to evaluate the risk of hip fracture in patients with PD. METHODS: Data were collected from the National Health Insurance Research Database of Taiwan. The study group included 394 patients with PD diagnosed in 1999-2000. The comparison cohort was comprised of 3940 age- and sex-matched patients from the same enrollment period. All patients were tracked from their index visits for eight years. RESULTS: Hip fracture developed in 10.4% of patients with PD and 4.1% of patients in the comparison cohort during the follow-up period. Log-rank test analysis showed a significantly higher rate of hip fracture in PD. The Cox proportional regression model showed an adjusted hazard ratio of 2.71 (95% confidence interval = 1.92 3.83, P < 0.001) for patients with PD. CONCLUSION: The hip fracture rate was as high as 10.4% in PD patients during 8 years follow-up period. While assessing the risk of hip fracture, PD should be taken into consideration. For those very high risk patients (elderly women with PD, osteoporosis, diabetes and diabetic neuropathy), many efforts should be made to prevent fracture. PMID- 22297126 TI - Diffusion tensor imaging: tract based spatial statistics study in essential tremor. AB - INTRODUCTION: Essential tremor (ET) is a common movement disorder with motor and non-motor symptoms. We aimed to investigate the neurodegenerative changes in the brain white matter of patients with ET using Diffusion Tensor Imaging (DTI). METHODS: Clinical and MRI data from 20 patients (5 women and 15 men; age-38.2 +/- 16.5 yrs) with ET and 17 controls (3 women and 14 men; age-40.7 +/- 16.5 yrs) were collected prospectively. The DTI data were analyzed using tract based spatial statistics (TBSS) software for tract wise analysis. Further region of interest (ROI) analysis was carried out in the genu of corpus callosum, anterior limb of internal capsule (ALIC), corticospinal tract (CS), and cerebellar peduncles. Effect of tremor severity, disease duration and age of onset on DTI metrics was also studied. RESULTS: Patients with ET in comparison to controls showed significant (P(corrected) < 0.05) increase of mean diffusivity and radial diffusivity in right frontoparietal white matter. Axial diffusivity increase was seen in bilateral cerebral hemispheres, thalamus, brainstem and cerebellar hemisphere white matter. No significant change in fractional anisotropy of the white matter was seen. ROI analysis also revealed abnormalities in the ALIC and cerebellar peduncles. There was no correlation between the severity of white matter changes and clinical tremor severity score as well as disease duration. CONCLUSIONS: This study provides in vivo evidence for axonal disintegration of the cerebral and cerebellar white matter fibres in patients with ET. PMID- 22297127 TI - Identification and possible role of a MYB transcription factor from saffron (Crocus sativus). AB - The MYB family is the most abundant group of transcription factors described for plants. Plant MYB genes have been shown to be involved in the regulation of many aspects of plant development. No MYB genes are described for saffron, the dried stigma of Crocus sativus, utilized as a colorant for foodstuffs. In this study, we used RACE-PCR to isolate a full length cDNA of 894bp with a 591bp open reading frame, encoding a putative CsMYB1 from C. sativus. Comparison between gDNA and cDNA revealed no introns. Homology studies indicated that the deduced amino acid sequence is similar to members of the R2R3 MYB subfamily. Expression analysis showed the presence of high transcript levels in stigma tissue and low levels in tepals, whereas no signal was detected in either anthers or leaves. The RT-PCR analysis revealed that CsMYB1 expression is developmentally regulated during stigma development. Furthermore, expression analysis in stigmas from different Crocus species showed a correlation with stigma morphology. No transcripts were found in stigma tissues of Crocus species characterized by branched stigma morphology. Taken together, these results suggest that CsMYB1 may be involved in the regulation of stigma morphology in Crocus. PMID- 22297128 TI - Enhancement of the photoelectric performance of dye-sensitized solar cells using Ag-doped TiO2 nanofibers in a TiO2 film as electrode. AB - For high solar conversion efficiency of dye-sensitized solar cells [DSSCs], TiO2 nanofiber [TN] and Ag-doped TiO2 nanofiber [ATN] have been extended to be included in TiO2 films to increase the amount of dye loading for a higher short circuit current. The ATN was used on affected DSSCs to increase the open circuit voltage. This process had enhanced the exit in dye molecules which were rapidly split into electrons, and the DSSCs with ATN stop the recombination of the electronic process. The conversion efficiency of TiO2 photoelectrode-based DSSCs was 4.74%; it was increased to 6.13% after adding 5 wt.% ATN into TiO2 films. The electron lifetime of DSSCs with ATN increased from 0.29 to 0.34 s and that electron recombination was reduced. PMID- 22297129 TI - Longitudinal study of unimanual actions and grasping forces during infancy. AB - Learning to grasp an object is an important milestone in neurological development during infancy. Several studies report development of reaching in infants but less attention is devoted to reaching with successful grasping and to development of grip force. This study investigates, in the first weeks of life, the development of palmar grasp both for assessment of unimanual/bimanual grasping actions in centrally and laterally placed objects and for measurement of exerted power grip force. We longitudinally examined ten infants from 18 weeks to 41 weeks, at 2-weeks intervals, with a toy placed in three positions (body midline, ipsilateral and contralateral shoulder). Our main aim was to study this development through an ecological approach. This was possible thanks to the use of the "biomechatronic gym", a new platform purposively developed for measuring reaching and grasping forces. These longitudinal trials showed a good level of acceptance and involvement by infants of the entire system. The results demonstrated a significant increase in unimanual power grip force between the 18th and 30th week followed by a flat period until the 41st week; we also ascertained an early tendency to play bimanually with centrally and laterally placed objects with a subsequent increase in all ages of unimanual successful power grasping both for central task and midline crossing. These developmental changes may be, in part, related to organism constraints such as maturation of the corticospinal tract. PMID- 22297131 TI - Caipirini: using gene sets to rank literature. AB - BACKGROUND: Keeping up-to-date with bioscience literature is becoming increasingly challenging. Several recent methods help meet this challenge by allowing literature search to be launched based on lists of abstracts that the user judges to be 'interesting'. Some methods go further by allowing the user to provide a second input set of 'uninteresting' abstracts; these two input sets are then used to search and rank literature by relevance. In this work we present the service 'Caipirini' (http://caipirini.org) that also allows two input sets, but takes the novel approach of allowing ranking of literature based on one or more sets of genes. RESULTS: To evaluate the usefulness of Caipirini, we used two test cases, one related to the human cell cycle, and a second related to disease defense mechanisms in Arabidopsis thaliana. In both cases, the new method achieved high precision in finding literature related to the biological mechanisms underlying the input data sets. CONCLUSIONS: To our knowledge Caipirini is the first service enabling literature search directly based on biological relevance to gene sets; thus, Caipirini gives the research community a new way to unlock hidden knowledge from gene sets derived via high-throughput experiments. PMID- 22297132 TI - Apoptosis of the fibrocytes type 1 in the spiral ligament and blood labyrinth barrier disturbance cause hearing impairment in murine cerebral malaria. AB - BACKGROUND: Experimental murine malaria has been shown to result in significant hearing impairment. Microscopic evaluation of the temporal bones of these animals has revealed regular morphology of the cochlea duct. Furthermore, the known vascular pathologic changes being associated with malaria could not be found. Immunohistochemistry for ICAM1 showed a strong marking in the stria vascularis, indicating a disturbance of the endocochlear potential. The aim of this study was to evaluate the role of apoptosis and the disturbance of the blood labyrinth barrier in the murine malaria associated hearing impairment. METHODS: The temporal bones of seven mice with cerebral malaria-four with hearing impairment, three without hearing impairment-were evaluated with immunohistochemistry for cleaved caspase 3 to detect apoptosis and connexin 26, a gap junction protein being a cornerstone in the endocochlear potassium recirculation. Furthermore five animals with cerebral malaria were treated with Evans blue prior to sacrification to detect disturbances of the blood labyrinth barrier. RESULTS: Cleaved caspase 3 could clearly be detected by immunohistochemistry in the fibrocytes of the spiral ligament, more intensively in animals with hearing impairment, less intensively in those without. Apoptosis signal was equally distributed in the spiral ligament as was the connexin 26 gap junction protein. The Evans blue testing revealed a strong signal in the malaria animals and no signal in the healthy control animals. CONCLUSION: Malfunction of the fibrocytes type 1 in the spiral ligament and disruption of the blood labyrinth barrier, resulting in a breakdown of the endocochlear potential, are major causes for hearing impairment in murine cerebral malaria. PMID- 22297133 TI - Co-expression vs. co-infection using baculovirus expression vectors in insect cell culture: Benefits and drawbacks. AB - The baculovirus expression vector system (BEVS) is a versatile and powerful platform for protein expression in insect cells. With the ability to approach similar post-translational modifications as in mammalian cells, the BEVS offers a number of advantages including high levels of expression as well as an inherent safety during manufacture and of the final product. Many BEVS products include proteins and protein complexes that require expression from more than one gene. This review examines the expression strategies that have been used to this end and focuses on the distinguishing features between those that make use of single polycistronic baculovirus (co-expression) and those that use multiple monocistronic baculoviruses (co-infection). Three major areas in which researchers have been able to take advantage of co-expression/co-infection are addressed, including compound structure-function studies, insect cell functionality augmentation, and VLP production. The core of the review discusses the parameters of interest for co-infection and co-expression with time of infection (TOI) and multiplicity of infection (MOI) highlighted for the former and the choice of promoter for the latter. In addition, an overview of modeling approaches is presented, with a suggested trajectory for future exploration. The review concludes with an examination of the gaps that still remain in co expression/co-infection knowledge and practice. PMID- 22297134 TI - Do we need biomarkers to predict the benefit of adding adjuvant taxanes for treatment of breast cancer? AB - The current understanding of the molecular biology of breast cancer presents an extremely complex portrait of the disease. Based on this knowledge, considerable efforts are being made to identify biomarkers that will predict the response to a specific treatment while minimizing the risk of unnecessary side effects. In breast cancer, the Ki67 index has been associated with poor prognosis and might play a relevant role in predicting benefit from adjuvant docetaxel, as observed in the article accompanying this editorial. Taxanes are one of the most active cytotoxic agents for breast cancer. However, the role of taxane-based chemotherapy as adjuvant treatment of early breast cancer remains controversial in some subsets of patients. For this reason, the Ki67 index might help to better define the group of patients who could have the optimal benefit. PMID- 22297135 TI - Novel monoclonal antibodies for identification of multicentric Castleman's disease; Kaposi's sarcoma-associated herpesvirus-encoded vMIP-I and vMIP-II. AB - Recent studies have indicated that vMIP-I and vMIP-II play important roles in the pathogenesis of Kaposi's sarcoma-associated herpesvirus (KSHV)-related diseases due to the effects of these proteins on vascularization. We developed monoclonal antibodies against KSHV-encoded viral macrophage inflammatory protein-I (vMIP-I) and vMIP-II to study these expression profiles and reveal the pathogenesis of KSHV-related diseases. The MAbs against vMIP-I and vMIP-II reacted to KSHV infected cell lines after lytic induction. Both vMIP-I and the vMIP-II gene products were detected 24 h post-induction with 12-O-tetradecanoylphorbol-13 acetate until 60 h in the cytoplasm of primary effusion lymphoma cell lines. In clinical specimens, both vMIP-I and vMIP-II gene products were detected in the tissues of patients with multicentric Castleman's disease. On the other hand, only vMIP-II was detected in a subset of Kaposi's sarcoma. We concluded that these antibodies might be powerful tools to elucidate the pathogenesis of KSHV related diseases. PMID- 22297136 TI - Cross-reactive antibody to swine influenza A(H3N2) subtype virus in children and adults before and after immunisation with 2010/11 trivalent inactivated influenza vaccine in Canada, August to November 2010. AB - In pre- and post-immunisation sera from children (17-120 months-old) and adults (20-59 years-old) immunised with 2010/11 trivalent inactivated influenza vaccine, we assessed age-related patterns of sero-susceptibility and vaccine-induced cross reactive antibodies to a representative swine H3N2 (swH3N2) and a related ancestral human H3N2 (A/Sydney/5/1997) influenza virus. Few children but a greater proportion of adults showed pre-immunisation haemagglutination inhibition titres >=40 to either virus. Titres increased with age among children but decreased in adults. Fewer than 20% showed a four-fold rise in antibody titres to either virus following immunisation. Further investigation is warranted to guide ongoing risk assessment and response to emerging swine H3N2 viruses. PMID- 22297137 TI - Outbreak of haemolytic uraemic syndrome due to Shiga toxin-producing Escherichia coli O104:H4 among French tourists returning from Turkey, September 2011. AB - Eight cases of diarrhoea, including two cases of haemolytic uraemic syndrome (HUS), were identified among 22 French tourists who travelled to Turkey in September 2011. A strain of Escherichia coli O104:H4 stx2-positive, eae-negative, hlyA-negative, aggR-positive, ESBL-negative was isolated from one HUS case. Molecular analyses show this strain to be genetically similar but not indistinguishable from the E. coli O104:H4 2011 outbreak strain of France and Germany. Although the source of infection was not identified, we conclude that the HUS cases had probably been infected in Turkey. PMID- 22297138 TI - Two invasive mosquito species, Aedes albopictus and Aedes japonicus japonicus, trapped in south-west Germany, July to August 2011. AB - Adult females of two invasive species, Aedes albopictus and Aedes japonicus japonicus, were collected for the first time in July and August 2011 in Germany. Previously, only immature stages of these species had been found in the country. Repeated detection of these species reveals the Upper Rhine Valley in south-west Germany to be a particularly sensitive region for the introduction and establishment of exotic mosquito species that needs careful observation. PMID- 22297139 TI - Influenza A(H1N1)pdm09 vaccination policies and coverage in Europe. AB - In August 2010 the Vaccine European New Integrated Collaboration Effort (VENICE) project conducted a survey to collect information on influenza A(H1N1)pdm09 vaccination policies and vaccination coverage in the European Union (EU), Norway and Iceland. Of 29 responding countries, 26 organised national pandemic influenza vaccination and one country had recommendations for vaccination but did not have a specific programme. Of the 27 countries with vaccine recommendations, all recommended it for healthcare workers and pregnant women. Twelve countries recommended vaccine for all ages. Six and three countries had recommendations for specific age groups in children and in adults, countries for specific adult age groups. Most countries recommended vaccine for those in new risk groups identified early in the pandemic such as morbid obese and people with neurologic diseases. Two thirds of countries started their vaccination campaigns within a four week period after week 40/2009. The reported vaccination coverage varied between countries from 0.4% to 59% for the entire population (22 countries); 3% to 68% for healthcare workers (13 countries); 0% to 58% for pregnant women (12 countries); 0.2% to 74% for children (12 countries). Most countries identified similar target groups for pandemic vaccine, but substantial variability in vaccination coverage was seen. The recommendations were in accordance with policy advice from the EU Health Security Committee and the World Health Organization. PMID- 22297142 TI - Score-based likelihood ratios for handwriting evidence. AB - Score-based approaches for computing forensic likelihood ratios are becoming more prevalent in the forensic literature. When two items of evidential value are entangled via a scorefunction, several nuances arise when attempting to model the score behavior under the competing source-level propositions. Specific assumptions must be made in order to appropriately model the numerator and denominator probability distributions. This process is fairly straightforward for the numerator of the score-based likelihood ratio, entailing the generation of a database of scores obtained by pairing items of evidence from the same source. However, this process presents ambiguities for the denominator database generation - in particular, how best to generate a database of scores between two items of different sources. Many alternatives have appeared in the literature, three of which we will consider in detail. They differ in their approach to generating denominator databases, by pairing (1) the item of known source with randomly selected items from a relevant database; (2) the item of unknown source with randomly generated items from a relevant database; or (3) two randomly generated items. When the two items differ in type, perhaps one having higher information content, these three alternatives can produce very different denominator databases. While each of these alternatives has appeared in the literature, the decision of how to generate the denominator database is often made without calling attention to the subjective nature of this process. In this paper, we compare each of the three methods (and the resulting score-based likelihood ratios), which can be thought of as three distinct interpretations of the denominator proposition. Our goal in performing these comparisons is to illustrate the effect that subtle modifications of these propositions can have on inferences drawn from the evidence evaluation procedure. The study was performed using a data set composed of cursive writing samples from over 400 writers. We found that, when provided with the same two items of evidence, the three methods often would lead to differing conclusions (with rates of disagreement ranging from 0.005 to 0.48). Rates of misleading evidence and Tippet plots are both used to characterize the range of behavior for the methods over varying sized questioned documents. The appendix shows that the three score-based likelihood ratios are theoretically very different not only from each other, but also from the likelihood ratio, and as a consequence each display drastically different behavior. PMID- 22297143 TI - Three-dimensional computer-assisted craniometrics: a comparison of the uncertainty in measurement induced by surface reconstruction performed by two computer programs. AB - Digital investigation of anthropological material through computed tomography (CT) offers several new opportunities in morphometrics. However, an object measured with computer-assisted methods does not necessarily exactly match the original one. The scanning and surface reconstruction of the object induce some alterations, and data acquisition is prone to measurement uncertainty. The purpose of this research is to evaluate the intra- and inter-observers variations in medical CT scan measurements of a known-size phantom and two dry crania. Two software packages, AMIRA and Treatment and Increased Vision for Medical Imaging (TIVMI), which use different techniques of surface reconstructions, were compared. The mean difference between the measurements was lower for TIVMI, using an objective algorithm based on the half-maximum height (HMH) protocol in three dimensions (3D). AMIRA can induce up to a 4% error in known measurements and 5% uncertainty in dry skull measurements. This study emphasises the risk of object shape alteration in each step of its digitisation. PMID- 22297144 TI - "Drop in" gastroscopy outpatient clinic--experience after 9 months. AB - BACKGROUND: Logistics handling referrals for gastroscopy may be more time consuming than the examination itself. For the patient, "drop in" gastroscopy may reduce uncertainty, inadequate therapy and time off work. METHODS: After an 8-9 month run-in period we asked patients, hospital staff and GPs to fill in a questionnaire to evaluate their experience with "drop in" gastroscopy and gastroscopy by appointment, respectively. The diagnostic gain was evaluated. RESULTS: 112 patients had "drop in" gastroscopy and 101 gastroscopy by appointment. The number of "drop in" patients varied between 3 and 12 per day (mean 6.5). Mean time from first GP consultation to gastroscopy was 3.6 weeks in the "drop in" group and 14 weeks in the appointment group. The half-yearly number of outpatient gastroscopies increased from 696 before introducing "drop in" to 1022 after (47% increase) and the proportion of examinations with pathological findings increased from 42% to 58%. Patients and GPs expressed great satisfaction with "drop in". Hospital staff also acclaimed although it caused more unpredictable working days with no additional staff. CONCLUSIONS: "Drop in" gastroscopy was introduced without increase in staff. The observed increase in gastroscopies was paralleled by a similar increase in pathological findings without any apparent disadvantages for other groups of patients. This should legitimise "drop in" outpatient gastroscopies, but it requires meticulous observation of possible unwanted effects when implemented. PMID- 22297145 TI - Prevalence of anti-Toxoplasma antibodies in patients with autoimmune diseases. AB - The identification of etiological factors in the induction of autoimmunity has remained elusive despite an enormous effort at dissection of the molecular structure of the target antigens and effector mechanisms. One characteristic feature of autoantigens is their repetitive structure as well as their conservation and evolution. Toxoplasma (T.) gondii is a primitive protozoan. We hypothesized that patients with autoimmune disease would have broad reactions against Toxoplasma antigens based on autoantigen conservation. To address this issue, we assessed serologic evidence of reactivity to Toxoplasma gondii along with a large profile of autoantibodies in patients with various autoimmune diseases (AID). We included sera of 1514 patients with 11 different AID collected from referral centers in Europe and Latin America as well as from 437 geographically matched controls, for the prevalence of anti Toxoplasma antibodies (ATxA) IgG and IgM and serum autoantibodies utilizing the BioPlex 2200 system (Bio- Rad Laboratories, USA). Serum ATxA IgG were positive in 42% of patients with AID versus 29% of controls (p < 0.0001). Among Europeans, ATxA IgG were associated with anti-phospholipid syndrome (APS; p < 0.0001), cryoglobulinemia (p < 0.0001), ANCA-associated vasculitides (p < 0.01), autoimmune thyroid diseases (p < 0.0001), systemic sclerosis (SSc; p < 0.0001) and rheumatoid arthritis (RA; p < 0.0001). Of note, Latin American RA sera exhibited similar frequency of ATxA IgG as controls. ATxA IgM were more prevalent in European patients with APS (p < 0.01), SSc (p < 0.05) and inflammatory bowel disease (IBD, p < 0.05) than in controls. Further, in AID patients the presence of ATxA correlated with autoantibodies characteristic of APS (anti- cardiolipin, B2GPI, complex of cardiolipin- B2GPI, prothrombin, phosphatydilethanolamine), and of SSc (anti centromere, Scl-70). Our findings suggest that T. gondii may contribute to the pathogenesis of AID. This interaction may depend on or explain observed geoepidemiological variance in AID. PMID- 22297146 TI - Monoclonal gammopathy related to Sjogren syndrome: a key marker of disease prognosis and outcomes. AB - OBJECTIVE: To analyze the monoclonal expression of SS through the detection of serum monoclonal immunoglobulins (mIgs) in a large series of patients with Sjogren syndrome (SS), focusing on the etiology, characterization and evolution of the monoclonal band and the association with SS clinical expression and outcomes. METHODS: Serum immunoelectrophoresis (IE) was performed to 408 consecutive patients who were evaluated by our unit between 1992 and 2011: 221 patients who fulfilled the 2002 American-European criteria for primary SS, 122 primary SS patients who fulfilled exclusively the 1993 European criteria and 65 patients with SS-associated hepatitis C virus infection. IE was performed at diagnosis and every year during the follow-up. RESULTS: Of the 221 patients with primary SS, 48 (22%) had monoclonal gammopathy. In the control groups, the prevalence was 16% in patients with SS who fulfilled the 1993 criteria (p > 0.05) and 52% in SS-HCV patients (p < 0.001). Monoclonal bands were characterized in 47/48 patients with primary SS: IgG (n = 21), IgM (n = 16), IgA (n = 5) and free light chains (n = 5); the light chain was kappa in 28 patients and lambda in 19 (kappa:lambda ratio 1.5). Primary SS patients with monoclonal gammopathy had a higher prevalence of parotidomegaly (38% vs 20%, p = 0.021), vasculitis (21% vs 6%, p = 0.003), neurological involvement (42% vs 23%, p = 0.016), higher mean values of circulating gammaglobulins (23.4 vs 20.6%, p = 0.026), ESR (56.6 vs 37.6 mm/h, p = 0.003), a higher prevalence of RF (69% vs 50%, p = 0.022), low C3 levels (24% vs 11%, p = 0.028), low C4 levels (24% vs 7%, p = 0.003), low CH50 activity (28% vs 11%, p = 0.008) and cryoglobulins (23% vs 8%, p = 0.012) compared with those without monoclonal gammopathy. Of the 48 patients with primary SS and monoclonal gammopathy, 8 developed hematologic neoplasia after a mean follow-up of 10 years, a higher prevalence than observed in patients without monoclonal gammopathy (17% vs 5%, p = 0.009). Survival rates according to the presence or absence of monoclonal gammopathy were 83% and 97%, respectively (log rank 0.004). CONCLUSION: Monoclonal gammopathy was detected in 22% of patients with primary SS fulfilling the 2002 criteria, with mIgGkappa being the most frequent type of band detected. In HCV-associated SS patients, the prevalence was higher (52%) with IgMkappa being the most prevalent band detected. Monoclonal gammopathy was associated with a higher prevalence of parotid enlargement, extraglandular features, hypergammaglobulinemia, cryoglobulinemia and related markers (rheumatoid factor, hypocomplementemia), and with a poor prognosis (development of neoplasia and death). PMID- 22297147 TI - Quality of life and brace-treated idiopathic scoliosis: a cross-sectional study performed at the Centre des Massues on a population of 120 children and adolescents. AB - OBJECTIVES: To determine the influence of orthopedic treatment on quality of life (QoL) in children and adolescents with idiopathic scoliosis and treated with either the carbon brace (CMCR, corset monocoque carbone respectant la respiration) or the Lyon brace. To compare these braces. PATIENTS AND METHODS: A cross-sectional study on a population of 120 patients with idiopathic scoliosis, visiting for routine evaluation following the onset of an orthopedic treatment at the Centre des Massues in Lyon. Eighty-two patients used the carbon brace and 38 patients used the Lyon brace. The patients completed the SRS-22 questionnaire (where a low score means a bad QoL), an evaluation scale of QoL specific to spinal deformities, and visual analogue scales (VAS) for pain, motivation and QoL ranging from 0 to 100mm. RESULTS: The QoL of Lyon brace-treated patients is significantly worse than that of patients treated with a carbon brace for the overall score (mean+/-SD, 4.05+/-0.37 vs 3.77+/-0.46, P=0.002) as well as for function (P=0.01), pain (P=0.001), and appearance (P=0.004). These results are confirmed by the VAS for QoL (P=0.001). CONCLUSION: The use of the carbon brace and of the Lyon brace induces a reduction in QoL whatever the evaluation tool, either SRS-22 or VAS. However, the use of the Lyon brace impairs QoL more than the use of the carbon brace. PMID- 22297148 TI - Advances in the understanding of the aetiology of Dupuytren's disease. AB - Dupuytren's disease is a fibroproliferative disease of the palmar fascia which has been described for centuries, yet the aetiology and pathophysiology remain poorly understood. Surgery and collagenase injections comprise the main therapeutic options but disease recurrence is common. We explore the evidence underlying the current disease theories and outline other potential therapeutic options. PMID- 22297149 TI - Porcine colon explants in the study of innate immune response to Entamoeba histolytica. AB - Human amebiasis is caused by the protozoan Entamoeba histolytica. This protozoan is responsible for muco-hemorrhagic diarrhoea and liver abscess in affected populations. E. histolytica can be asymptomatic commensally confined to the intestinal lumen or can result in invasion of the colonic mucosa leading to ulceration and/or liver abscesses. Recently, human colonic explants have been identified as valuable in the study of host-parasite interactions. Here we investigated the potential of porcine colonic explants as an alternative to human tissues which are far less available. Porcine colonic explants were cultured with two strains of E. histolytica, one virulent (HM1:IMSS) and one avirulent (Rahman). Results from histopathological and real-time PCR analysis showed that porcine explants cultured with virulent ameba trophozoites react similarly to their human counterparts with an invasion of the tissue by the trophozoites and the triggering of typical innate immune response against the parasite. On the contrary, explants cultured with avirulent ameba trophozoites were preserved. The study open the way to the use of porcine colonic explants in the study of the complex interactions between the parasite and the host. PMID- 22297150 TI - Replication of ketamine's antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. AB - BACKGROUND: Currently, no pharmacological treatments for bipolar depression exist that exert rapid (within hours) antidepressant or antisuicidal effects. We previously reported that intravenous administration of the N-methyl-D-aspartate antagonist ketamine produced rapid antidepressant effects in patients with treatment-resistant bipolar depression. The present study sought to replicate this finding in an independent sample. METHODS: In this double-blind, randomized, crossover, placebo-controlled study, 15 subjects with DSM-IV bipolar I or II depression maintained on therapeutic levels of lithium or valproate received a single intravenous infusion of either ketamine hydrochloride (.5 mg/kg) or placebo on 2 test days 2 weeks apart. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale, which was used to rate overall depressive symptoms at baseline; at 40, 80, 110, and 230 minutes postinfusion; and on days 1, 2, 3, 7, 10, and 14 postinfusion. RESULTS: Within 40 minutes, depressive symptoms, as well as suicidal ideation, significantly improved in subjects receiving ketamine compared with placebo (d = .89, 95% confidence interval = .61-1.16, and .98, 95% confidence interval = .64-1.33, respectively); this improvement remained significant through day 3. Seventy-nine percent of subjects responded to ketamine and 0% responded to placebo at some point during the trial. The most common side effect was dissociative symptoms, which occurred only at the 40-minute time point. CONCLUSIONS: This study replicated our previous finding that patients with bipolar depression who received a single ketamine infusion experienced a rapid and robust antidepressant response. In addition, we found that ketamine rapidly improved suicidal ideation in these patients. PMID- 22297151 TI - Association of COL25A1 with comorbid antisocial personality disorder and substance dependence. AB - BACKGROUND: Antisocial personality disorder (ASPD) is a psychiatric disorder characterized by a long-term pattern of manipulating, exploiting, or violating the rights of others. METHODS: Subjects ascertained for genetic studies of substance dependence (SD) and diagnosed with ASPD and comorbid SD were included in a two-stage genetic association study. In the discovery stage, 627 single nucleotide polymorphisms (SNPs) located in 179 candidate genes for addiction were analyzed in a case-control cohort and family-based cohort. The significant findings were replicated in an independent case-control cohort. RESULTS: One SNP, rs13134663, in the collagen XXV alpha 1 gene (COL25A1) was significantly associated with ASPD in both African Americans and European Americans (smallest p values were .0002 and .0004, respectively). There was also evidence of association with the same SNP in independent samples of African American and European American cases and control subjects (p = .035 and .033, respectively). Analysis of the combined set of case-control subjects yielded an allelic p value of 9 * 10(-6) with odds ratio (95% confidence interval) of 1.3 (1.16, 1.47) (smallest p = 1 * 10(-7); Bonferroni threshold p = .00012). CONCLUSIONS: The COL25A1 gene, located at chromosome 4q25, encodes the collagen-like Alzheimer amyloid plaque component precursor, a type II transmembrane protein specifically expressed in neurons; it co-localizes with amyloid beta in senile plaques in Alzheimer disease brains. This SNP maps to the transcription factor binding site and is conserved in 17 vertebrates, including mice and rats. Our findings suggest that COL25A1 may be associated with ASPD, especially in the context of SD. PMID- 22297152 TI - Two common mutations (p.Gln832X and c.663+1G>C) account for about a third of the DYSF mutations in Korean patients with dysferlinopathy. AB - Dysferlinopathy refers to autosomal recessive muscular dystrophies caused by mutations in dysferlin gene (DYSF). It includes two major distinct disorders, Miyoshi myopathy and limb-girdle muscular dystrophy type 2B. Twenty-three Korean patients were recruited. Full sequence analysis of DYSF detected 10 novel and 9 known mutations. The p.Gln832X showed the highest allele frequency (10/46) as a unique recurrent mutation among Korean population, and two common mutations (p.Gln832X and c.663+1G>C) accounted for 34.8% of the identified mutations. Korean DYSF mutations appeared to cluster in the N-terminal region. Notably, none of homozygous mutations was found in this study. Clinical features were similar to previous reports showing onset in early adulthood, high serum CK and inflammatory reactions on muscle pathology. In Miyoshi myopathy, gastrocnemius muscle was first affected on muscle CT scans, and anterior lower legs and thigh muscles were then affected with disease progression. Despite the genetic variety of DYSF mutations, clinical features were rather invariable among the patients. PMID- 22297153 TI - Improving the measurement of neighbourhood characteristics through systematic observation: inequalities in smoking as a case study. AB - Systematic observation is increasingly used as a method to measure neighbourhood characteristics thought to influence health inequalities. This article reports on the theory-driven development of a new observation tool composed of reflective indicators of neighbourhood characteristics believed to influence inequalities in smoking. We also report the results of generalisability analyses conducted to estimate the reliability (inter-rater reliability and temporal stability) of the observation tool. We use the reliability results to reflect on the quality of the measures and on the theoretical anchors of the tool. We conclude by making recommendations to improve measures collected through systematic observation. PMID- 22297154 TI - Increases in solar conversion efficiencies of the ZrO2 nanofiber-doped TiO2 photoelectrode for dye-sensitized solar cells. AB - In this paper, in order to improve the efficiency of dye-sensitized solar cells, we introduced zirconia [ZrO2] nanofibers into a mesoporous titania [TiO2] photoelectrode. The photoelectrode consists of a few weight percent of ZrO2 nanofibers and a mesoporous TiO2 powder. The mixed ZrO2 nanofibers and the mesoporous TiO2 powder possessed a larger surface area than the corresponding mesoporous TiO2 powder. The optimum ratio of the ZrO2 nanofiber was 5 wt.%. The 5 wt.% ZrO2-mixed device could get a short-circuit photocurrent density of 15.9 mA/cm2, an open-circuit photovoltage of 0.69 V, a fill factor of 0.60, and a light-to-electricity conversion efficiency of 6.5% under irradiation of AM 1.5 (100 mW/cm2). PMID- 22297155 TI - Attractive toxic sugar bait (ATSB) methods decimate populations of Anopheles malaria vectors in arid environments regardless of the local availability of favoured sugar-source blossoms. AB - BACKGROUND: Attractive toxic sugar bait (ATSB) methods are a new and promising "attract and kill" strategy for mosquito control. Sugar-feeding female and male mosquitoes attracted to ATSB solutions, either sprayed on plants or in bait stations, ingest an incorporated low-risk toxin such as boric acid and are killed. This field study in the arid malaria-free oasis environment of Israel compares how the availability of a primary natural sugar source for Anopheles sergentii mosquitoes: flowering Acacia raddiana trees, affects the efficacy of ATSB methods for mosquito control. METHODS: A 47-day field trial was conducted to compare impacts of a single application of ATSB treatment on mosquito densities and age structure in isolated uninhabited sugar-rich and sugar-poor oases relative to an untreated sugar-rich oasis that served as a control. RESULTS: ATSB spraying on patches of non-flowering vegetation around freshwater springs reduced densities of female An. sergentii by 95.2% in the sugar-rich oasis and 98.6% in the sugar-poor oasis; males in both oases were practically eliminated. It reduced daily survival rates of female An. sergentii from 0.77 to 0.35 in the sugar-poor oasis and from 0.85 to 0.51 in the sugar-rich oasis. ATSB treatment reduced the proportion of older more epidemiologically dangerous mosquitoes (three or more gonotrophic cycles) by 100% and 96.7%, respectively, in the sugar-poor and sugar rich oases. Overall, malaria vectorial capacity was reduced from 11.2 to 0.0 in the sugar-poor oasis and from 79.0 to 0.03 in the sugar-rich oasis. Reduction in vector capacity to negligible levels days after ATSB application in the sugar poor oasis, but not until after 2 weeks in the sugar-rich oasis, show that natural sugar sources compete with the applied ATSB solutions. CONCLUSION: While readily available natural sugar sources delay ATSB impact, they do not affect overall outcomes because the high frequency of sugar feeding by mosquitoes has an accumulating effect on the probability they will be attracted to and killed by ATSB methods. Operationally, ATSB methods for malaria vector control are highly effective in arid environments regardless of competitive, highly attractive natural sugar sources in their outdoor environment. PMID- 22297156 TI - Fields and forests in flames: lead and mercury emissions from wildfire pyrogenic activity. PMID- 22297157 TI - Transgenic enrichment of mouse embryonic stem cell-derived progenitor motor neurons. AB - Embryonic stem cells (ESCs) hold great potential for replacing neurons following injury or disease. The therapeutic and diagnostic potential of ESCs may be hindered by heterogeneity in ESC-derived populations. Drug selection has been used to purify ESC-derived cardiomyocytes and endothelial cells but has not been applied to specific neural lineages. In this study we investigated positive selection of progenitor motor neurons (pMNs) through transgenic expression of the puromycin resistance enzyme, puromycin N-acetyl-transferase (PAC), under the Olig2 promoter. The protein-coding region in one allele of Olig2 was replaced with PAC to generate the P-Olig2 cell line. This cell line provided specific puromycin resistance in cells that express Olig2, while Olig2(-) cells were killed by puromycin. Positive selection significantly enriched populations of Olig2(+) pMNs. Committed motoneurons (MNs) expressing Hb9, a common progeny of pMNs, were also enriched by the end of the selection period. Selected cells remained viable and differentiated into mature cholinergic MNs and oligodendrocyte precursor cells. Drug resistance may provide a scalable and inexpensive method for enriching desired neural cell types for use in research applications. PMID- 22297158 TI - Metabolic shift of polyphosphate-accumulating organisms with different levels of polyphosphate storage. AB - Previous studies have shown that polyphosphate-accumulating organisms (PAOs) are able to behave as glycogen-accumulating organisms (GAOs) under different conditions. In this study we investigated the behavior of a culture enriched with Accumulibacter at different levels of polyphosphate (poly-P) storage. The results of stoichiometric ratios Gly(degraded)/HAc(uptake), PHB(synthesized)/HAc(uptake), PHV(synthesized)/HAc(uptake) and P(release)/HAc(uptake) confirmed a metabolic shift from PAO metabolism to GAO metabolism: PAOs with high poly-P content used the poly-P to obtain adenosine tri-phosphate (ATP), and glycogen (Gly) to obtain nicotinamide adenine dinucleotide (NADH) and some ATP. In a test where poly-P depletion was imposed on the culture, all the acetate (HAc) added in each cycle was transformed into polyhydroxyalkanoate (PHA) despite the decrease of poly-P inside the cells. This led to an increase of the Gly(degraded)/HAc(uptake) ratio that resulted from a shift towards the glycolytic pathway in order to compensate for the lack of ATP formed from poly-P hydrolysis. The shift from PAO to GAO metabolism was also reflected in the change in the PHA composition as the poly-P availability decreased, suggesting that polyhydroxyvalerate (PHV) is obtained due to the consumption of excess reducing equivalents to balance the internal NADH, similarly to GAO metabolism. Fluorescence in situ hybridization analysis showed a significant PAO population change from Type I to Type II Accumulibacter as the poly-P availability decreased in short term experiments. This work suggests that poly-P storage levels and GAO-like metabolism are important factors affecting the competition between different PAO Types in enhanced biological phosphorus removal systems. PMID- 22297159 TI - A link between oxytocin and serotonin in humans: supporting evidence from peripheral markers. AB - Pharmacological studies indicate a functional interaction between the serotonergic and oxytocinergic systems. In particular, some selective serotonin (5-HT) reuptake inhibitors, such as citalopram and fluvoxamine, seem to exert part of their antidepressant effects through oxytocin (OT) release. Further, the administration of fenfluramine, a serotonergic agonist, to healthy subjects increases plasma OT levels. Interestingly, immunocytochemical and double immunofluorescent techniques revealed a high degree of overlap between 5-HT transporter (SERT)-labeled fibers and OT-containing cells in the paraventricular and supraoptic nuclei of primate hypothalamus. These findings suggest that the influence of 5-HT on OT system might be mediated by SERT. In this study, we explored the possible existence of a link between OT and SERT in human subjects, by means of two peripheral markers, the platelet SERT, as measured by [3H] paroxetine ([3H]-Par) binding, and plasma OT levels. As far as [3H]-Par binding parameters are concerned, the Bmax (mean +/- SD, fmol/mg protein) was 1155 + 130 and the Kd (mean +/- SD, nM) was 1.31 +/- 0.61. The OT plasma levels (mean +/- SD, pg/ml) were 1.14 +/- 1.07. A significant and positive correlation was found between plasma OT levels and Kd values (correlation coefficient: r: 0.466, p = .038). This result represents the first evidence of an interaction between OT and SERT, as measured by [3H]-Par binding, at peripheral levels in humans. Given the several activities mediated by both OT and 5-HT, such a relationship might provide new perspectives and insights into psychiatric disorders and/or social relationship disturbances, as well as novel treatment strategies overcoming and/or integrating the serotonergic paradigm. PMID- 22297160 TI - Changes in trend of antipsychotics prescription in patients treated with cholinesterase inhibitors after warnings from Italian Medicines Agency. Results from the EPIFARM-Elderly Project. AB - The objective of the study was to assess the trend of antipsychotic prescription in elderly patients taking cholinesterase inhibitors (ChEIs) from 2002 to 2008 and the changes subsequent to two main official warnings issued by the Italian Medicines Agency to restrict their use. Elderly patients aged 65-94years who received at least one prescription of ChEIs between 1 January 2002 and 31 December 2008 were selected. We used data on prescriptions from the Lombardy Region Drug Administrative Database (Italy). The first prescription of one ChEI was used as the index day to calculate the prescription of an antipsychotic. The prescription of atypical antipsychotics in patients exposed to ChEIs declined from 21.0% in 2002 to 14.6% in 2008 (OR 0.92; 95%CI:0.90, 0.94; p<0.001), while the prescribing prevalence of typicals slightly increased (OR 1.08; 95%CI:1.03, 1.13; p=0.001). In relation to the two warnings, the prevalence of patients who received a prescription of antipsychotics was significantly lower in 2005 than 2004 (23.1% vs. 28.0%; OR 0.79; 95%CI:0.73-0.86; p<0.001) and in 2007 than 2006 (19.4% vs. 23.0%; OR 0.79; 95%CI:0.73-0.86; p<0.001). After the first safety warning the prevalence of prescriptions for risperidone and olanzapine dropped significantly, and there was a significant increase for quetiapine. Haloperidol prescriptions increased, especially after the second warning. Despite regulatory warnings issued to discourage the use of antipsychotics, they are still frequently prescribed to patients taking ChEIs. Awaiting further studies to clarify their therapeutic role, physicians should prescribe antipsychotics very cautiously and only after careful risk-benefit assessment. PMID- 22297161 TI - Age of blood and recipient factors determine the severity of transfusion-related acute lung injury (TRALI). AB - INTRODUCTION: Critical care patients frequently receive blood transfusions. Some reports show an association between aged or stored blood and increased morbidity and mortality, including the development of transfusion-related acute lung injury (TRALI). However, the existence of conflicting data endorses the need for research to either reject this association, or to confirm it and elucidate the underlying mechanisms. METHODS: Twenty-eight sheep were randomised into two groups, receiving saline or lipopolysaccharide (LPS). Sheep were further randomised to also receive transfusion of pooled and heat-inactivated supernatant from fresh (Day 1) or stored (Day 42) non-leucoreduced human packed red blood cells (PRBC) or an infusion of saline. TRALI was defined by hypoxaemia during or within two hours of transfusion and histological evidence of pulmonary oedema. Regression modelling compared physiology between groups, and to a previous study, using stored platelet concentrates (PLT). Samples of the transfused blood products also underwent cytokine array and biochemical analyses, and their neutrophil priming ability was measured in vitro. RESULTS: TRALI did not develop in sheep that first received saline-infusion. In contrast, 80% of sheep that first received LPS-infusion developed TRALI following transfusion with "stored PRBC." The decreased mean arterial pressure and cardiac output as well as increased central venous pressure and body temperature were more severe for TRALI induced by "stored PRBC" than by "stored PLT." Storage-related accumulation of several factors was demonstrated in both "stored PRBC" and "stored PLT", and was associated with increased in vitro neutrophil priming. Concentrations of several factors were higher in the "stored PRBC" than in the "stored PLT," however, there was no difference to neutrophil priming in vitro. CONCLUSIONS: In this in vivo ovine model, both recipient and blood product factors contributed to the development of TRALI. Sick (LPS infused) sheep rather than healthy (saline infused) sheep predominantly developed TRALI when transfused with supernatant from stored but not fresh PRBC. "Stored PRBC" induced a more severe injury than "stored PLT" and had a different storage lesion profile, suggesting that these outcomes may be associated with storage lesion factors unique to each blood product type. Therefore, the transfusion of fresh rather than stored PRBC may minimise the risk of TRALI. PMID- 22297162 TI - Synchronous phenology of juvenile Ixodes scapularis, vertebrate host relationships, and associated patterns of Borrelia burgdorferi ribotypes in the midwestern United States. AB - To elucidate features of enzootic maintenance of the Lyme disease bacterium that affect human risk of infection, we conducted a longitudinal study of the phenology of the vector tick, Ixodes scapularis, at a newly invaded site in the north-central United States. Surveys for questing ticks and ticks parasitizing white-footed mice and eastern chipmunks revealed that I. scapularis nymphal and larval activity peaked synchronously in June and exhibited an atypical, unimodal seasonality. Adult seasonal activity was bimodal and distributed evenly in spring and fall. We discuss implications of these phenology data for the duration of the I. scapularis life cycle. Densities of Borrelia burgdorferi-infected, questing nymphs were comparable to those found in endemic areas elsewhere in the midwestern and northeastern U.S. Molecular genetic diversity of B. burgdorferi infecting these ticks and rodents was assessed by analysis of the ribosomal spacer types (RSTs). RST 1, a clade that includes strains with highly pathogenic properties, was relatively uncommon (3.4%) in contrast to the northeastern U.S., whereas less pathogenic ribotypes of the RST 2 and 3 clades were more common. These features of the ecology of this midwestern Lyme disease system likely contribute to the lower incidence of Lyme disease in humans in the Upper Midwest compared with that of the Northeast owing to reduced exposure to pathogenic strains of B. burgdorferi. PMID- 22297164 TI - Preconditioning with Ginkgo biloba (EGb 761(r)) provides neuroprotection through HO1 and CRMP2. AB - Ginkgo biloba/EGb 761(r) (EGb 761) is a popular and standardized natural extract used worldwide for the treatment of many ailments. Although EGb 761 is purported to have a plethora of benefits, here, we were interested to study the neuroprotective properties of EGb 761 and its components and determine whether nuclear factor E2 (Nrf2)/heme oxygenase 1 (HO1) induction of the collapsin response mediator protein 2 (CRMP2) pathway contributes to neuroprotection. Mice were pretreated with EGb 761 or one of its constituents (bilobalide, ginkgolide A, ginkgolide B, and terpene free material [TFM]) for 7days and then subjected to transient middle cerebral artery occlusion (tMCAO) and 48 h of reperfusion. All components except TFM significantly reduced infarct volumes and neurologic deficits. Next, we examined the antioxidant and neuritogenic properties of EGb 761 in primary neurons. Compared with vehicle-treated cells, pretreatment with EGb 761 significantly enhanced the survival of neurons exposed to tertiary butylhydroperoxide (t-BuOOH), hydrogen peroxide (H2O2), and N-methyl-D-aspartate (NMDA). Bilobalide and ginkgolide A also protected cells against NMDA-induced excitotoxicity. Immunofluorescence and Western blot analysis showed that EGb 761 pretreatment significantly increased the protein expression levels of Nrf2, HO1, GAPDH, beta-actin, CRMP2, and histone H3 during t-BuOOH-induced oxidative stress. These findings suggest that EGb 761 not only has antioxidant activity but also neuritogenic potential. Demonstrating such effects for possible drug discovery may prove beneficial in stroke and ischemic brain injury. PMID- 22297165 TI - Electron slowing-down spectra in water for electron and photon sources calculated with the Geant4-DNA code. AB - Recently, a very low energy extension was added to the Monte Carlo simulation toolkit Geant4. It is intended for radiobiological modeling and is referred to as Geant4-DNA. Its performance, however, has not been systematically benchmarked in terms of transport characteristics. This study reports on the electron slowing down spectra and mean energy per ion pair, the W-value, in water for monoenergetic electron and photon sources calculated with Geant4-DNA. These quantities depend on electron energy, but not on spatial or angular variables which makes them a good choice for testing the model of energy transfer processes. The spectra also have a scientific value for radiobiological modeling as they describe the energy distribution of electrons entering small volumes, such as the cell nucleus. Comparisons of Geant4-DNA results with previous studies showed overall good agreement. Some differences in slowing-down spectra between Geant4-DNA and previous studies were found at 100 eV and at approximately 500 eV that were attributed to approximations in models of vibrational excitations and atomic de-excitation after ionization by electron impact. We also found that the high-energy part of the Geant4-DNA spectrum for a 1 keV electron source was higher, and the asymptotic high-energy W-value was lower than previous studies reported. PMID- 22297163 TI - Cell signaling and mitochondrial dynamics: Implications for neuronal function and neurodegenerative disease. AB - Nascent evidence indicates that mitochondrial fission, fusion, and transport are subject to intricate regulatory mechanisms that intersect with both well characterized and emerging signaling pathways. While it is well established that mutations in components of the mitochondrial fission/fusion machinery can cause neurological disorders, relatively little is known about upstream regulators of mitochondrial dynamics and their role in neurodegeneration. Here, we review posttranslational regulation of mitochondrial fission/fusion enzymes, with particular emphasis on dynamin-related protein 1 (Drp1), as well as outer mitochondrial signaling complexes involving protein kinases and phosphatases. We also review recent evidence that mitochondrial dynamics has profound consequences for neuronal development and synaptic transmission and discuss implications for clinical translation. PMID- 22297166 TI - IgM autoantibodies to distinct apoptosis-associated antigens correlate with protection from cardiovascular events and renal disease in patients with SLE. AB - Emerging evidence suggests that there are IgM-autoantibodies that may play protective roles in SLE. While IgM are often considered polyreactive, we postulate that there are distinct sets of IgM-autoantibodies of defined autoreactive specificities relevant to different features of SLE. We examined the relationships between levels of IgM natural autoantibodies (NAbs) to apoptosis associated phosphorylcholine (PC) or malondialdehyde (MDA) antigens, with lupus associated autoantibodies and features of disease, in 120 SLE patients. IgM anti PC was significantly higher in patients with low disease activity and less organ damage determined by the SELENA-SLEDAI, the physician's evaluation and the SLICC damage score. Furthermore, IgM anti-PC was significantly higher in patients without cardiovascular events. In contrast, IgM anti-cardiolipin and IgM anti dsDNA were significantly higher in patients without renal disease. These results support the hypothesis that some IgM autoantibodies are part of a natural immune repertoire that provide homeostatic functions and protection from certain clinical lupus features. PMID- 22297167 TI - Exploring the role of the epigenome in multiple sclerosis: a window onto cell specific transcriptional potential. AB - The field of epigenomics involves the study of chromatin, the three dimensional complex of DNA, protein and non-coding RNAs that determines the accessibility of DNA by the transcriptional machinery. The epigenome varies from cell to cell and reflects the effect of external stimuli on cell fate and cell state. Thanks to emerging platforms and analysis methods, the systematic characterization of chromatin conformation throughout the genome has begun and has yielded several reference epigenome maps for a growing number of cell types. Such maps are enabling insights into the correlation architecture of different epigenomic marks: a number of discrete chromatin states are found across different cell types. The combination of these reference maps and robust platforms for genome wide data generation has introduced a new era in which studies of human disease are becoming feasible. Little is known about the role of the epigenome in MS, but it is likely that, as in other inflammatory disease, susceptibility factors and events along the course of the disease will alter the chromatin state of different cell types in patients with MS. Here, we review different strategies for the characterization of the epigenome and how these strategies could be used to implement new studies to explore how alterations of chromatin architecture establish a dysregulated transcriptional state in the context of MS. PMID- 22297168 TI - A comparison of systemic breast cancer therapy utilization in Canada (British Columbia), Scotland (Dundee), and Australia (Western Australia) with models of "optimal" therapy. AB - BACKGROUND: Different jurisdictions report different breast cancer treatment rates. Evidence-based optimal utilization models may be specific to the derived population. We compared predicted optimal with actual endocrine and chemotherapy utilization in British Columbia, Canada; Dundee, Scotland; and Perth, Western Australia. DESIGN: Data were analyzed for differences in demography, tumour, and treatment. Epidemiological data were fitted to published Australian optimal radiotherapy utilization trees and region-specific optimal treatment rates were calculated. Optimal and actual systemic therapy rates from 2 population-based and 1 institution-based cancer registries were compared for patients diagnosed with breast cancer between 2000-2004, and 2002 for British Columbia. RESULTS: Chemotherapy rates differed between British Columbia (32%), Perth (29%), and Dundee (24%, p = 0.014). Endocrine therapy rates were similar between British Columbia (56%), Perth (59%), and Dundee (64%, p > 0.05). Actual utilization rates were lower than optimal estimates for chemotherapy, but higher for endocrine therapy. Region-specific optimal utilization rates at diagnosis varied between 50 56% for chemotherapy, and 49-54% for endocrine therapy. Variation was attributed to local differences in demographics, and tumour stage. CONCLUSION: Actual treatment rates varied. There was lower than estimated optimal chemotherapy use but higher than expected use of endocrine therapy. PMID- 22297169 TI - Where do hands go? An audit of sequential hand-touch events on a hospital ward. AB - BACKGROUND: Reservoirs of pathogens could establish themselves at forgotten sites on a ward, posing a continued risk for transmission to patients via unwashed hands. AIM: To track potential spread of organisms between surfaces and patients, and to gain a greater understanding into transmission pathways of pathogens during patient care. METHODS: Hand-touch activities were audited covertly for 40 * 30 min sessions during summer and winter, and included hand hygiene on entry; contact with near-patient sites; patient contact; contact with clinical equipment; hand hygiene on exit; and contact with sites outside the room. FINDINGS: There were 104 entries overall: 77 clinical staff (59 nurses; 18 doctors), 21 domestic staff, one pharmacist and five relatives. Hand-hygiene compliance among clinical staff before and after entry was 25% (38/154), with higher compliance during 20 summer periods [47%; 95% confidence interval (CI): 35.6-58.8] than during 20 winter periods (7%; 95% CI: 3.2-14.4; P < 0.0001). More than half of the staff (58%; 45/77) touched the patient. Staff were more likely to clean their hands prior to contact with a patient [odds ratio (OR): 3.44; 95% CI: 0.94-16.0); P = 0.059] and sites beside the patient (OR: 6.76; 95% CI: 1.40 65.77; P = 0.0067). Nearly half (48%; 37/77) handled patient notes and 25% touched the bed. Most frequently handled equipment inside the room were intravenous drip (30%) and blood pressure stand (13%), and computer (26%), notes trolley (23%) and telephone (21%) outside the room. CONCLUSION: Hand-hygiene compliance remains poor during covert observation; understanding the most frequent interactions between hands and surfaces could target sites for cleaning. PMID- 22297170 TI - Are commercially available Geobacillus stearothermophilus biological indicators an appropriate standard for hydrogen peroxide vapour systems in hospitals? PMID- 22297171 TI - Quantitative assessment of new cell proliferation in the dentate gyrus and learning after isoflurane or propofol anesthesia in young and aged rats. AB - There is a growing body of evidence showing that a statistically significant number of people experience long-term changes in cognition after anesthesia. We hypothesize that this cognitive impairment may result from an anesthetic-induced alteration of postnatal hippocampal cell proliferation. To test this hypothesis, we investigated the effects of isoflurane and propofol on new cell proliferation and cognition of young (4 month-old) and aged (21 month-old). All rats were injected intraperitoneally (IP) with 50 mg/kg of 5-bromo-2-deoxyuridine (BrdU) immediately after anesthesia. A novel appetitive olfactory learning test was used to assess learning and memory two days after anesthesia. One week after anesthesia, rats were euthanized and the brains analyzed for new cell proliferation in the dentate gyrus, and proliferation and migration of newly formed cells in the subventricular zone to the olfactory bulb. We found that exposure to either isoflurane (p=0.017) or propofol (p=0.006) decreased hippocampal cell proliferation in young, but not in aged rats. This anesthetic induced decrease was specific to new cell proliferation in the hippocampus, as new cell proliferation and migration to the olfactory bulb was unaffected. Isoflurane anesthesia produced learning impairment in aged rats (p=0.044), but not in young rats. Conversely, propofol anesthesia resulted in learning impairment in young (p=0.01), but not in aged rats. These results indicate that isoflurane and propofol anesthesia affect postnatal hippocampal cell proliferation and learning in an age dependent manner. PMID- 22297172 TI - Cellular consequences of the expression of Alzheimer's disease-causing presenilin 1 mutations in human neuroblastoma (SH-SY5Y) cells. AB - Mutations in the presenilin 1 (PS1) gene lead to early-onset Alzheimer's disease with the S170F mutation causing the earliest reported age of onset. Expression of this, and other PS1 mutations, in SH-SY5Y cells resulted in significant loss of cellular viability compared to control cells. Basal Ca2+ concentrations in PS1 mutants were never lower than controls and prolonged incubation in Ca2+ -free solutions did not deplete Ca2+ stores, demonstrating there was no difference in Ca2+ leak from endoplasmic reticulum (ER) stores in PS1 mutants. Peak muscarine evoked rises of [Ca2+]i were variable, but the integrals were not significantly different, suggesting, while kinetics of Ca2+ store release might be affected in PS1 mutants, store size was similar. However, when Ca2+ -ATPase activity was irreversibly inhibited with thapsigargin, the S170F and DeltaE9 cells showed larger capacitative calcium entry indicating a direct effect on Ca2+ influx pathways. There was no significant effect of any of the mutations on mitochondrial respiration. Amyloid beta(Abeta(1-40)) secretion was reduced, and Abeta(1-42) secretion increased in the S170F cells resulting in a very large increase in the Abeta42/40 ratio. This, rather than any potential disruption of ER Ca2+ stores, is likely to explain the extreme pathology of this mutant. PMID- 22297173 TI - Post-weaning social isolation of female rats, anxiety-related behavior, and serotonergic systems. AB - Our previous studies have shown that post-weaning social isolation of male rats leads to sensitization of serotonergic systems and increases in anxiety-like behavior in adulthood. Although studies in humans suggest that females have an increased sensitivity to stress and risk for the development of neuropsychiatric illnesses, most studies involving laboratory rats have focused on males while females have been insufficiently studied. The objective of this study was to investigate the effects of post-weaning social isolation on subsequent responses of an anxiety-related dorsal raphe nucleus (DR)-basolateral amygdala system to pharmacological challenge with the anxiogenic drug, N-methyl-beta-carboline-3 carboxamide (FG-7142; a partial inverse agonist at the benzodiazepine allosteric site on the gamma-aminobutyric acid (GABA)(A) receptor). Juvenile female rats were reared in isolation or in groups of three for a 3-week period from weaning to mid-adolescence, after which all rats were group-reared for an additional 2 weeks. We then used dual immunohistochemical staining for c-Fos and tryptophan hydroxylase in the DR or single immunohistochemical staining for c-Fos in the basolateral amygdala. Isolation-reared rats, but not group-reared rats, injected with FG-7142 had increased c-Fos expression within the basolateral amygdala and in serotonergic neurons in the dorsal, ventrolateral, caudal and interfascicular parts of the DR relative to appropriate vehicle-injected control groups. These data suggest that post-weaning social isolation of female rats sensitizes a DR basolateral amygdala system to stress-related stimuli, which may lead to an increased sensitivity to stress- and anxiety-related responses in adulthood. PMID- 22297174 TI - Cold-inducible RNA binding protein inhibits H2O2-induced apoptosis in rat cortical neurons. AB - OBJECTIVE: The expression cold-inducible RNA-binding protein (CIRP) is significantly enhanced in neurons under hypothermia, but its roles remain unclear. This study aims to investigate whether the cerebral protection under hypothermia is mediated by the CIRP-mediated inhibition of neuronal apoptosis. METHODS: Primary rat cortical neurons were isolated, cultured, and transduced with lentiviral CIRP-RNAi. Apoptosis of the transduced neurons was induced with 100 MUmol/L H2O2, the treated cells were divided into two groups, and cultured in 37 degrees C or 32 degrees C incubator respectively. Cell viability was detected by MTT colorimetric assay. Neuronal apoptosis was detected by flow cytometry after labeling the cells with Hoechst 33342 and Annexin V-FITC/PI. The protein expressions of CIRP, activated caspase-3, and thioredoxin (TRX) were detected by Western blot. RESULTS: Under 32 degrees C, CIRP protein is significantly induced in cortical neurons; the expression of activated caspase-3 decreases, while the TRX expression increases. The rate of neuronal apoptosis is 4.5+/-0.8%. Under 37 degrees C, CIRP expression is evidently reduced in cortical neurons; the expression of activated caspase-3 is significantly enhanced with reduced level of TRX expression. The rate of neuronal apoptosis reaches 53.5+/ 1.7% (P < 0.05, compared to that in 32 degrees C group). CONCLUSIONS: The induction of CIRP protein in rat cortical neurons under hypothermia inhibits H2O2 induced neuronal apoptosis and thereby exerts neuroprotective effect, which forms one of the cerebral protective pathways under hypothermia. PMID- 22297175 TI - Mechanisms of Mg2+ inhibition of BzATP-dependent Ca2+ responses in THP-1 monocytes. AB - We have recently reported effects of Mg2+ to confer neuroprotection against toxicity of purinergic stimulated microglia and THP-1 monocytes. To examine mechanisms underlying neuroprotection, we have studied Mg2+ modulation of transient changes in intracellular Ca2+ ([Ca2+]i) in THP-1 cells induced by P2X7R agonist 2',3'-[benzoyl-4-benzoyl]-ATP (BzATP). Application of BzATP caused a rapid transient increase in [Ca2+]i followed by a prolonged component. The time course of the secondary slower phase was significantly reduced with Ca2+-free extracellular solution, with treatment of THP-1 cells by the P2X7R antagonist, oxATP or with exposure of cells to the store-operated channel (SOC) inhibitor, SKF96365. These results suggest that Ca2+ influx, mediated by both the P2X7R or by SOC, contribute to the slow component of [Ca2+]i. Treatment of THP-1 cells with 10 mMMg2+ was highly effective in reducing the time course of BzATP-induced Ca2+ decay; unlike the other modulatory protocols, Mg2+ markedly inhibited the amplitudes of slow and rapid components. In addition, acute application of Mg2+ during BzATP-induced responses elicited in the presence of either oxATP or SKF96365 to block respective P2X7R and SOC contributions, rapidly attenuated [Ca2+]i to baseline levels. Priming of cells with the inflammatory stimulus LPS/IFN-gamma markedly enhanced the slower, but not rapid, phase of BzATP-induced [Ca2+]i with application of 10 mMMg2+ inhibiting both components of response. A model is proposed to account for BzATP stimulation of both ionotropic P2XR and metabotropic P2YR which provides a mechanistic basis for elevated Mg2+ anti inflammatory and neuroprotective actions in inflamed brain. PMID- 22297176 TI - Effects of the selective kainate receptor antagonist ACET on altered sensorimotor gating in a genetic model of reduced NMDA receptor function. AB - The pathophysiology of schizophrenia may involve reduced NMDA receptor function. Accordingly, experimental models of NMDA receptor hypofunction may be useful for testing potential new antipsychotic agents and for characterizing neurobiological abnormalities relevant to schizophrenia. We demonstrated previously that mice under-expressing the NR1 subunit of the NMDA receptor show supersensitive behavioral responses to kainic acid and that a kainate receptor antagonist normalized altered behaviors in the mutant mice (NR1(neo/neo)). The present work examined effects of another selective kainate receptor antagonist, (S)-1-(2-Amino 2-carboxyethyl)-3-(2-carboxy-5-phenylthiophene-3-yl-methylpyrimidine-2,4-dione (ACET), on altered behavioral phenotypes in the genetic model of NMDA receptor hypofunction. ACET, at a dose of 15 mg/kg, partially reversed the deficits in prepulse inhibition produced by the mutation. The 15 mg/kg dose of ACET was also effective in reversing behavioral effects of the selective kainate agonist ATPA. However, ACET did not significantly reduce the increased locomotor activity and rearing behavior observed in the NR1(neo/neo) mice. These findings show that a highly selective kainate receptor antagonist can affect the deficits in sensorimotor gating in the NR1(neo/neo) mice. The results also provide further support for the idea that selective kainate receptor antagonists could be novel therapeutic candidates for schizophrenia. PMID- 22297177 TI - An ERP investigation into the strategic regulation of the fluency heuristic during recognition memory. AB - The goal of the present study was to determine whether masked repetition priming affects ERPs differently depending on whether or not participants are biased by task conditions to interpret enhanced perceptual fluency as evidence of prior study. Participants studied a list of words either in the visual modality or in the auditory modality and then performed a visual recognition memory test while ERPs were recorded. During the test, half the stimuli were preceded by a briefly presented matching prime word and half were preceded by a briefly presented non matching prime word. Unlike in previous behavioral studies, masked repetition priming led to a reduction in positive recognition responses following auditory study, and had no effect following visual study, although post hoc analyses suggest that participants who received the visual study list may have relied on fluency to make some of their recognition decisions. Masked repetition priming also led to positive ERPs during two time windows-an early 300-500 ms window and a later 500-700 ms window. During the later time window, masked repetition priming exhibited a frontal scalp distribution that was most pronounced for participants who received the auditory study list. We suggest that this late frontal effect reflects participants' tendency to reject enhanced perceptual fluency as evidence of prior study. PMID- 22297178 TI - Multipolar radiofrequency ablation using 4-6 applicators simultaneously: a study in the ex vivo bovine liver. AB - In this study the volume and shape of coagulation zones after multipolar radiofrequency ablation (RFA) with simultaneous use of 4-6 applicators in the ex vivo bovine liver were investigated. The RF-applicators were positioned in 13 different configurations to simulate ablation of large solitary tumors and simultaneous ablation of multiple lesions with 120 kJ of applied energy/session. In total, 110 coagulation zones were induced. Standardized measurements of the volume and shape of the coagulation zones were carried out on magnetic resonance images and statistically analyzed. The coagulation zones induced with solitary applicators and with 2 applicators were imperceptibly small and incomplete, respectively. At 20mm applicator distance, the total ablated volume was significantly larger if all applicators were arranged in a single group compared to placement in 2 distant applicator groups, each consisting of 3 applicators (p=.001). The mean total coagulated volume ranged from immeasurably small (if 6 solitary applicators were applied simultaneously) to 74.7 cc (if 6 applicators at 30 mm distance between neighboring applicators were combined to a single group). Applicator distance, number and positioning array impacted time and shape. The coagulation zones surrounding groups with 4-6 applicators were regularly shaped, homogeneous and completely fused, and the axial diameters were almost constant. In conclusion, multipolar RFA with 4-6 applicators is feasible. The multipolar simultaneous mode should be applied for large and solitary lesions only, small and multiple tumors should be ablated consecutively in standard multipolar mode with up to 3 applicators. PMID- 22297179 TI - Why current evidence is against flow diverters for treatment of carotid blowout syndrome. PMID- 22297180 TI - Using low tube voltage (80kVp) quadruple phase liver CT for the detection of hepatocellular carcinoma: two-year experience and comparison with Gd-EOB-DTPA enhanced liver MRI. AB - PURPOSE: To validate the diagnostic performance of quadruple phase low tube voltage liver CT through the comparison with Gd-EOB-DTPA enhanced liver MRI for the detection of HCC. MATERIALS AND METHODS: Non-obese patients (38 men, eight women) with 68 HCCs underwent quadruple-phase CT at 16 MDCT (using low tube voltage, 80kVp; moderately high tube current, 280mAs) and Gd-EOB-DTPA-enhanced 3T MRI. Three observers independently and randomly reviewed the CT and MR images on a tumor-by-tumor basis. The diagnostic accuracy of these techniques for detecting HCC was assessed using alternative free-response receiver operating characteristic analysis. Sensitivity and positive predictive values were evaluated. The mean effective doses for the low dose CT were also evaluated. RESULTS: The areas under the ROC curves were 0.963, 0.959, and 0.941 for low dose CT and 0.981, 0.982, and 0.976 for MRI. Differences in Az of the two techniques for each observer were not statistically significant (P>.05). Differences in sensitivity and positive predictive values between the two techniques for each observer were not also statistically significant: sensitivity (86.8%, 82.4%, 85.3% for CT and 95.6%, 94.1%, 91.2% for MRI) and positive predictive values (92.2%, 90.3%, 89.2% for CT and 92.9%, 92.8%, 92.5% for MRI). Six HCCs (8.8%) in five patients were observed only on hepatobiliary phase of MRI, and all were smaller than 1.5cm. The mean effective dose for CT was approximately 10.2mSv. CONCLUSIONS: Quadruple-phase low-dose liver CT (80kVp, 280mAs) had relatively good diagnostic performance for detecting HCC in non-obese patients. Because no significant difference was observed between low-dose CT and MRI, the use of low dose liver CT can be justified based on its reduced radiation effects. PMID- 22297181 TI - Carpal tunnel syndrome assessed with diffusion tensor imaging: comparison with electrophysiological studies of patients and healthy volunteers. AB - The main goal of this study was to investigate the applicability of parameters derived from diffusion tension imaging (DTI) in diagnosing carpal tunnel syndrome (CTS). Forty subjects were recruited, of which 19 were normal controls and 21 belonged to the CTS group. DTI of median nerves evaluated at 4 levels of the wrist (distal radius, pisiform bone, middle portion of the carpal tunnel, and hamate bone) and conventional MRI of the wrist was performed in normal and CTS subjects in two finger postures (extension and flexion). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were derived from DTI, and parameters related to abnormal hyperintensity of the median nerve were derived from conventional MRI. Electrophysiological tests, including nerve conduction velocity and F wave were also performed for comparison. The results of FA and ADC measurements did not depend on the measuring location and finger posture. Mean FA was decreased while mean ADC was increased by CTS. FA and ADC at the middle portion of the carpal tunnel was 0.47+/-0.05 and 1.37+/-0.12 (*10(-3) mm2/s) for the control group and 0.42+/-0.04 and 1.50+/-0.15 (*10(-3) mm2/s) for the CTS group, respectively. The linear correlations of FA and ADC versus electrophysiological indicators of CTS were significant (R2 ranged from 0.09 to 0.36), indicating FA and ADC from DTI had significant correlation with the existence and severity of CTS. PMID- 22297182 TI - Mucosa-associated lymphoid tissue lymphoma of the salivary glands: MR imaging findings including diffusion-weighted imaging. AB - PURPOSE: The purpose of this study was to describe MR findings including diffusion-weighted (DW) imaging findings in patients with mucosa-associated lymphoid tissue (MALT) lymphoma of the salivary glands. MATERIALS AND METHODS: Ten patients with histologically proven MALT lymphoma of the salivary glands were included. All patients underwent 1.5-T MR imaging, six of the ten underwent DW imaging, nine underwent CT, and eight (18)F-fluorodeoxyglucose (FDG) PET/CT. MR images were reviewed for numbers, locations, sizes, MR imaging characteristics, and apparent diffusion coefficients (ADCs). Calcium deposition and maximum standardized uptake values (SUVmax) were also assessed. RESULTS: Twenty-six tumors, ranging in number from 1 to 5 (mean, 2.6), were identified. Nine patients had tumors in the parotid glands and one in the submandibular glands. Tumors were found bilaterally in 7 patients and unilaterally in three. Tumors ranged in size from 0.6 to 5.5cm (mean, 1.8cm). Ten (38%) tumors had intratumoral cystic formations and 8 (31%) had ill-demarcated margins. DW images showed hyperintensity with extremely low ADCs (range, 0.48-0.82 [*10(-3)mm(2)/s]; mean, 0.64) for solid components of all 19 tumors in the 6 examined patients. Calcium deposition was found in one (4%) tumor on CT. SUVmax variously ranged from 1.3 to 17.7 (mean, 6.3). CONCLUSION: Salivary gland MALT lymphomas were often found bilaterally and were occasionally accompanied by intratumoral cystic formations and ill-demarcated margins. DW imaging may play a supplementary role in the diagnosis of lymphoma, because it showed restricted water molecule diffusion, whereas PET/CT showed indeterminate findings. PMID- 22297183 TI - Does MRI add to ultrasound in the assessment of disorders of sex development? AB - OBJECTIVE: The objective of the study was to evaluate the need of magnetic resonance imaging and using different approaches (transabdominal, endoluminal and transperineal) in the proper assessment of disorders of sex development regarding gonadal detection and gender differentiation. SUBJECTS AND METHODS: Twenty five patients with abnormalities of sex disorders were included. They were classified into two groups according to the time of clinical presentation: Group 1 (early onset) included eight cases. Their age ranged from one month to 12 years (mean age=3.0). They presented with overt genital ambiguity of clitoral hypertrophy in a phenotypic female, non palpable testes or micropenis in a phenotypic male. Group 2 (late onset) included 17 cases. Their age ranged from 16 to 33 years (mean age 18.1). This group presented by distressing puberty symptoms of primary amenorrhea in a female phenotype or undescended testis and behaving as a male. Cases were subjected to Ultrasound and MR imaging examinations. Imaging results were correlated results of chromosomal and hormonal assays as well as laparoscopy findings. RESULTS: The study included: 10/25 cases (40%) of female pseudo hermaphroditism, 13/25 cases (52%) of male pseudo-hermaphroditism, one case (4%) of true hermaphroditism and one case (4%) of pure gonadal dysgenesis. The accuracy of multi approach ultrasound was 89.8% compared to 85.7% in MR imaging. CONCLUSION: Ultrasound should be considered the initial screening modality in the assessment of developmental sex disorders. MRI examination could be reserved for gonad identification when ultrasound examination fails to do so and for corrective surgery guidance. PMID- 22297184 TI - Contrast timing in computed tomography: effect of different contrast media concentrations on bolus geometry. AB - OBJECTIVE: To assess the effect of low-osmolar, monomeric contrast media with different iodine concentrations on bolus shape in aortic CT angiography. MATERIALS AND METHODS: Repeated sequential computed tomography scanning of the descending aorta of eight beagle dogs (5 male, 12.7+/-3.1kg) was performed without table movement with a standardized CT scan protocol. Iopromide 300 (300mgI/mL), iopromide 370 (370mgI/mL) and iomeprol 400 (400mgI/mL) were administered via a foreleg vein with an identical iodine delivery rate of 1.2gI/s and a total iodine dose of 300mgI/kg body weight. Time-enhancement curves were computed and analyzed. RESULTS: Iopromide 300 showed the highest peak enhancement (445.2+/-89.1 HU), steepest up-slope (104.2+/-17.5 HU/s) and smallest full width at half maximum (FWHM; 5.8+/-1.0s). Peak enhancement, duration of FWHM, enhancement at FWHM and up-slope differed significantly between iopromide 300 and iomeprol 400 (p<0.05). Except for enhancement at FWHM there were no significant differences between iopromide 300 and iopromide 370 and iopromide 370 and iomeprol 400 (p>0.05). CONCLUSIONS: Low viscous iopromide 300 results in a better defined bolus with a significantly higher peak enhancement, steeper up-slope and smaller FWHM when compared to iomeprol 400. These characteristics potentially affect contrast timing. PMID- 22297185 TI - Diffusion weighted MR imaging in patients with HCC and liver cirrhosis after administration of different gadolinium contrast agents: is it still reliable? AB - PURPOSE: Diffusion weighted imaging (DWI) is an emerging technique for abdominal MR and usually performed before intravenous contrast injection. Recent studies performed in patients with normal liver function have shown that DWI can be performed after gadolinium administration. Aim of this study was to compare DWI before and after administration of different gadolinium compounds in patients with HCC and liver cirrhosis. MATERIALS AND METHODS: 15 patients with known HCC and liver cirrhosis underwent liver MRI at 1.5T (Magnetom Avanto, Siemens) including DWI on day 1 before and after administration of gadobutrol (Gadovist((r))) and on day 2 after administration of EOB-Gadolinium-DTPA (Primovist((r))). Signal to noise ratios (SNR) and contrast to noise ratios (CNR) of HCC lesions were determined for all DWI data sets. Furthermore, ADC values were compared using a Wilcoxon test. A p-value <0.05 indicated statistically significant differences. RESULTS: There were no statistically significant differences regarding SNR pre-contrast (mean: 48.1), after gadobutrol (mean: 47.7) or after EOB-Gadolinium-DTPA (mean: 50.0; values for b=50s/mm(2)). Similarly, no significant differences were found for CNR (average values:34.4 vs. 32.3 vs. 30.7; b=50s/mm(2)) nor for ADC-values (mean: 1.5 vs. 1.4 vs. 1.5*10( 3)mm(2)/s) of HCC. CONCLUSION: There is no significant difference regarding DWI in patients with cirrhosis before and after contrast injection. Hence, it is reliable to run DWI after gadolinium either as an alternative for unsuccessful pre-contrast DWI or as a gap filler to spare time in EOB-Gadolinium-DTPA imaging. PMID- 22297186 TI - Ossification variants of the femoral condyles are not associated with osteochondritis dissecans. AB - PURPOSE: To determine if ossification variants of the femoral condyles involving the subchondral bone plate are associated with osteochondritis dissecans (OCD). MATERIALS AND METHODS: The prevalence of ossification variants of the unaffected femoral condyle in 116 patients (aged 9-14 years) with unicondylar OCD on MRI (magnetic resonance imaging) of the knee was compared to a control group of 579 patients (aged 9-14 years) without OCD. The evolution of the ossification variants in both groups was studied by reviewing follow-up MR imaging side by side with the baseline study. RESULTS: The prevalence of ossification variants in the unaffected condyle in patients with OCD (12.9%) and in the control group of patients without OCD (12.6%) was similar (p=0.88). Evolution of ossification variants to OCD was not seen on follow-up MRI examinations. All variants had decreased in size or were no longer visible. CONCLUSION: Ossification variants of the femoral condyle that involve the subchondral bone plate are not associated with OCD. CLINICAL RELEVANCE STATEMENT: Ossification variants are not associated with OCD, indicating that routine MRI follow-up in affected children is not mandatory. PMID- 22297187 TI - The role of morbidity and mortality meetings in interventional radiology. AB - PURPOSE: To understand the current practice of interventional radiology (IR) morbidity and mortality (M&M) meetings among interventional radiologists in Europe, and to develop a set of results-based recommendations to increase the prevalence of IR M&M meetings. MATERIALS AND METHODS: Online electronic surveys were sent to members of the Cardiovascular and Interventional Radiology Society of Europe (CIRSE). Each survey consisted of 18 questions pertaining to IR M&M meetings. RESULTS: A total of 150 CIRSE members responded to the survey. Approximately 47% of respondents held IR M&M meetings in their departments. Among those who held IR M&M meetings, 42% held them monthly and 68% rated the quality of the meetings as good or excellent. Of those who did not have M&M meetings, 94% were interested in incorporating M&M meetings into their future practice. The most common reasons for not holding IR M&M meetings were lack of time (68%) and small IR practice groups (43%). A total of 85% were interested in learning more about IR M&M meetings. The preferred method of education about M&M meetings included annual radiology meetings (44%), peer-reviewed articles in radiology journals (31%), websites (26%), and newsletters (15%). CONCLUSIONS: The data demonstrate that although current practice of M&M meetings in European IR departments is limited, the majority of respondents believe that M&M meetings are beneficial to their practice. There is a need for guidelines or standards of practice to incorporate such meetings in IR departments to prevent medical errors, which may ultimately lead to enhanced patient safety and outcomes. PMID- 22297188 TI - Which types of stretching modifies biomechanical dimensions of a muscle-tendon unit? PMID- 22297189 TI - Can universal insecticide-treated net campaigns achieve equity in coverage and use? the case of northern Nigeria. AB - BACKGROUND: Insecticide-treated nets (ITNs) are effective tools for malaria prevention and can significantly reduce severe disease and mortality due to malaria, especially among children under five in endemic areas. However, ITN coverage and use remain low and inequitable among different socio-economic groups in sub-Saharan Africa, particularly in Nigeria. Several strategies have been proposed to increase coverage and use and reduce inequity in Nigeria, including free distribution campaigns recently conducted by the Nigerian federal government. Using data from the first post-campaign survey, the authors investigated the effect of the mass free distribution campaigns in achieving equity in household ownership and use of ITNs. METHODS: A post-campaign survey was undertaken in November 2009 in northern Nigeria to assess the effect of the campaigns in addressing equity across different socio-economic groups. The survey included 987 households randomly selected from 60 clusters in Kano state. Using logistic regression and the Lorenz concentration curve and index, the authors assessed equity in ITN coverage and use. RESULTS: ITN ownership coverage increased from 10% before the campaigns to 70%-a more than fivefold increase. The campaigns reduced the ownership coverage gap by 75%, effectively reaching parity among wealth quintiles (Concentration index 0.02, 95% CI (-0.02 ; 0.05) versus 0.21 95%CI (0.08 ; 0.34) before the campaigns). ITN use (individuals reporting having slept under an ITN the night before the survey visit) among individuals from households owning at least one ITN, was 53.1% with no statistically significant difference between the lowest, second, third and fourth wealth quintiles and the highest wealth quintile (lowest: odds ratio (OR) 0.87, 95% confidence interval (CI) (0.67 ; 1.13); second: OR 0.85, 95% CI (0.66 ; 1.24); third: OR 1.10 95% CI (0.86 ; 1.4) and fourth OR 0.91 95% CI (0.72 ; 1.15). CONCLUSION: The campaign had a significant impact by increasing ITN coverage and reducing inequity in ownership and use. Free ITN distribution campaigns should be sustained to increase equitable coverage. These campaigns should be supplemented with other ITN distribution strategies to cover newborns and replace aging nets. PMID- 22297191 TI - Emphysematous gastritis: A young diabetic's recovery. AB - INTRODUCTION: Emphysematous gastritis (EG) is a rare and often fatal disorder involving infection of the gastric wall by gas-forming organisms. PRESENTATION OF CASE: We present the case of a 25-year-old diabetic man with severe gastroparesis, who complained of vomiting and right upper quadrant pain. The surgical consultant exam in the emergency department revealed a tender but not acute abdomen. On abdominal computed tomographic imaging, there was gas throughout the wall of the stomach but no evidence of gastric perforation. The patient was treated non-operatively with antibiotics, bowel rest, serial abdominal exams, and upper endoscopy (EGD). DISCUSSION: EG has been associated with overall mortality rates exceeding 50%. Early recognition and administration of antibiotics is essential to reduce mortality risk. Indications for laparotomy include perforation or uncontrolled sepsis. CONCLUSION: EG can occur in diabetics with gastroparesis complicated by a bezoar and hyperemesis. Gastric pneumatosis is not an absolute indication for celiotomy as antibiotics and surgical vigilance may be appropriate and curative therapy. PMID- 22297190 TI - Changes over time in the relationship between symptoms of asthma, rhinoconjunctivitis and eczema: a global perspective from the International Study of Asthma and Allergies in Childhood (ISAAC). AB - BACKGROUND: The International Study of Asthma and Allergies in Childhood (ISAAC) identified trends in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema over a seven-year period. We hypothesised that environmental influences on the three diseases are different and therefore investigated the correlation over time between trends in the prevalence of these diseases and their combinations at centre and individual level. METHODS: Centre level analyses were correlations between time trends in the prevalence of symptoms. At an individual level, odds ratios were calculated for associations between symptoms between Phases One and Three. We also investigated potential effect modification in the younger versus older age group; male versus female; and by average Gross National Income per capita (GNI). RESULTS: Both phases were completed in 66 centres in 37 countries for the 6-7 year age group and in 106 centres in 56 countries for the 13-14 year age group. We found that the correlations in time trends were stronger for the older age group than the younger one. Between symptoms of diseases, correlations of time trends were the strongest for rhinoconjunctivitis with eczema and weakest for eczema with asthma. The relationship between the three diseases was generally consistent over the seven year period, and there was little association found with average GNI. CONCLUSIONS: Despite some increase in the proportion of children with symptoms of asthma, rhinoconjunctivitis and eczema, the pattern between the three diseases has not changed much, suggesting that similar factors may be affecting them at a global level. PMID- 22297192 TI - Acute appendicitis presenting as chest pain. AB - INTRODUCTION: Abdominal pain is the primary presenting complaint of patients with acute appendicitis. Acute appendicitis presenting as chest pain is extremely rare and according to our search such presentation due to herniation of appendix into thorax through congenital diaphragmatic defect has not yet been reported. PRESENTATION OF CASE: We present a case of a 12year old male child who presented with acute chest pain. ECG was suggestive of ischemic changes. Echocardiogram and cardiac enzymes were within normal limits. Chest X-ray and gastrograffin contrast study confirmed the diagnosis of congenital diaphragmatic hernia. On exploration inflamed appendix was found herniated through the diaphragm along with caecum, ascending colon and transverse colon. Histology confirmed the diagnosis of acute appendicitis. DISCUSSION: Acute appendicitis may sometimes have very varied and rare presentation. In late presenting CDH, the most important factor responsible for acute or chronic presentation seems to be the type of herniated viscera. CONCLUSION: This report presents a rare case of late-presenting CDH with herniated appendix along with caecum, ascending colon and transverse colon. Unusual presentation of chest pain was due to an attack of acute appendicitis. Late-presenting CDH is a very intriguing defect with a wide spectrum of clinical manifestations. It should be suspected in cases of unexplained acute or chronic respiratory or gastrointestinal symptoms, and abnormal chest radiographic findings. The prognosis is favorable with correct diagnosis and prompt surgical repair. PMID- 22297193 TI - Characterization of epitaxial GaAs MOS capacitors using atomic layer-deposited TiO2/Al2O3 gate stack: study of Ge auto-doping and p-type Zn doping. AB - Electrical and physical properties of a metal-oxide-semiconductor [MOS] structure using atomic layer-deposited high-k dielectrics (TiO2/Al2O3) and epitaxial GaAs [epi-GaAs] grown on Ge(100) substrates have been investigated. The epi-GaAs, either undoped or Zn-doped, was grown using metal-organic chemical vapor deposition method at 620 degrees C to 650 degrees C. The diffusion of Ge atoms into epi-GaAs resulted in auto-doping, and therefore, an n-MOS behavior was observed for undoped and Zn-doped epi-GaAs with the doping concentration up to approximately 1017 cm-3. This is attributed to the diffusion of a significant amount of Ge atoms from the Ge substrate as confirmed by the simulation using SILVACO software and also from the secondary ion mass spectrometry analyses. The Zn-doped epi-GaAs with a doping concentration of approximately 1018 cm-3 converts the epi-GaAs layer into p-type since the Zn doping is relatively higher than the out-diffused Ge concentration. The capacitance-voltage characteristics show similar frequency dispersion and leakage current for n-type and p-type epi-GaAs layers with very low hysteresis voltage (approximately 10 mV).PACS: 81.15.Gh. PMID- 22297194 TI - Ectopic cholecystitis: a case report. PMID- 22297195 TI - Torsion of an accessory hepatic lobe mimicking a mesenteric tumor. PMID- 22297197 TI - Sorption of PAHs and PCBs to activated carbon: coal versus biomass-based quality. AB - The addition of activated carbon (AC) is an increasingly popular method for pollutant immobilization, and the AC material can be made of biomass or coal/fossil feedstock. The aim of the present study was to investigate whether there are differences between pollutant sorption to biomass and coal-based AC in the presence and absence of sediment. Through N(2) and CO(2) adsorption to probe surface area and pore size it was shown that the biomass-based AC had a stronger dominance of narrow pores in the size range 3.5-15A than the anthracite-based material. In the absence of sediment, sorption isotherms for the probe compounds pyrene and PCB-101 showed stronger sorption for the biomass-based AC (logarithmic Freundlich coefficients 8.15 for pyrene; 9.91 for PCB-101) than for the anthracite-based one (logarithmic Freundlich coefficients 7.20 and 9.70, respectively). In the presence of sediment, the opposite trend was observed, with the stronger sorption for anthracite-based AC. Thus, the presence of competing and/or pore-blocking sediment constituents reduces sorption to a larger extent for biomass-derived AC (factor of 5 for pyrene to almost 100 for PCB-101) than for anthracite-based AC (no reduction for pyrene to factor of 5 for PCB-101). This difference is tentatively attributed to the difference in pore size distribution, narrow pores being more prone to clogging, and could have implications for remediation feasibility with AC from different sources. PMID- 22297198 TI - Assessment of occupational exposure to benzene, toluene and xylenes in urban and rural female workers. AB - OBJECTIVES: This is the first research study to compare among female, non-smoker workers: (a) the exposure to benzene, toluene and xylenes (BTXs) in urban air during work in the street (traffic policewomen, TP) vs. work in vehicles (police drivers, PD); (b) the exposure to BTXs in urban environments (in street and in car) vs. rural environments (roadwomen, RW); (c) the values of blood benzene, urinary trans, trans muconic acid (t,t-MA) and urinary S-phenylmercapturic acid (S-PMA) in urban areas (in street and in car) vs. rural areas. METHODS: Passive personal samplings and data acquired using fixed monitoring stations located in different areas of the city were used to measure environmental and occupational exposure to BTXs during the work shift in 48 TP, 21 PD and 22 RW. In the same study subjects, blood benzene, t,t-MA and S-PMA were measured at the end of each work shift. RESULTS: Personal exposure of urban workers to benzene seemed to be higher than the exposure measured by the fixed monitoring stations. Personal exposure to benzene and toluene was (a) similar among TP and PD and (b) higher among urban workers compared to rural workers. Personal exposure to xylenes was (a) higher in TP than in PD and (b) higher among urban workers compared to rural workers. Blood benzene, t,t-MA and S-PMA levels were similar among TP and PD, although the blood benzene level was significantly higher in urban workers compared to rural workers. In urban workers, airborne benzene and blood benzene levels were significantly correlated. CONCLUSIONS: Benzene is a human carcinogen, and BTXs are potential reproductive toxins at low dose exposures. Biological and environmental monitoring to assess exposure to BTXs represents a preliminary and necessary tool for the implementation of preventive measures for female subjects working in outdoor environments. PMID- 22297199 TI - Putting theory of mind in its place: psychological explanations of the socio emotional-communicative impairments in autistic spectrum disorder. AB - In this review, the history of the theory of mind (ToM) theory of autistic spectrum disorder (ASD) is outlined (in which ToM is indexed by success on false belief tasks), and the explanatory power and psychological causes of impaired ToM in ASD are critically discussed. It is concluded that impaired ToM by itself has only limited explanatory power, but that explorations of the psychological precursors of impaired ToM have been fruitful in increasing understanding of mindreading impairments in ASD (where 'mindreading' refers those abilities that underlie triadic interaction as well as ToM). It is argued that early explanations of impaired mindreading are untenable for various reasons, but that impairments of dyadic interaction in ASD that could lead to impaired ability to represent others' mental states may be the critical psychological cause, or causes, of impaired ToM. The complexity of causal routes to impaired ToM is emphasized. PMID- 22297200 TI - Parent and child perspectives on the nature of anxiety in children and young people with autism spectrum disorders: a focus group study. AB - Anxiety disorders are common among children and young people with autism spectrum disorders (ASD). Despite growing knowledge about the prevalence, phenomenology and treatment of anxiety disorders, relatively little is understood about the nature and impact of anxiety in this group and little is known about autism specific factors that may have a role in the increased prevalence of anxiety disorders. In this exploratory study, we report on a series of five focus groups with 17 parents of children and adolescents with ASD and anxiety. Across groups, parents gave strikingly similar descriptions of the triggers and behavioural signs associated with anxiety. Another consistent finding was that many parents reported that their children had great difficulty expressing their worries verbally and most showed their anxiety through changes in their behaviour. The impact of anxiety was reported to often be more substantial than the impact of ASD itself. The implications of the focus group findings are discussed in relation to existing literature. PMID- 22297201 TI - Enhancing parental well-being and coping through a family-centred short course for Iranian parents of children with an autism spectrum disorder. AB - Parents of children with autism spectrum disorders (ASD) generally experience high levels of stress and report poorer emotional well-being and family functioning compared to parents of children with other disabilities. They also tend to rely on emotional rather than problem-focused coping strategies. Seven group-based sessions were offered to two groups of parents of children with ASD in Iran (37 in all). In addition to providing information about ASD emphasis was placed on families sharing their experiences and learning from one another. A pre post, cross-over design was used to evaluate the specific impact of the course. The changes found among the parents in the first group were replicated with the second group. Moreover the changes were sustained up to 15 weeks after the course ended. Although there were variations across the parents, in general they reported feeling less stress, had better emotional wellbeing and family functioning and made more use of problem-focused coping strategies. The changes were attributed mainly to an increase in the informal supports among the parents and their feelings of empowerment. A resource pack has been developed to enable the group sessions to be easily repeated and for facilitators to be trained in its use. PMID- 22297202 TI - The impact of child problem behaviors of children with ASD on parent mental health: the mediating role of acceptance and empowerment. AB - Raising a child with an autism spectrum disorder (ASD) has often been associated with higher levels of parenting stress and psychological distress, and a number of studies have examined the role of psychological processes as mediators of the impact of child problem behavior on parent mental health. The current study examined the relations among child problem behavior, parent mental health, psychological acceptance, and parent empowerment. Participants included 228 parents of children diagnosed with ASD, 6-21 years of age. As expected, psychological acceptance and empowerment were negatively related to the severity of parent mental health problems. When acceptance and empowerment were compared with each other through a test of multiple mediation, only psychological acceptance emerged as a significant partial mediator of the path between child problem behavior and parent mental health problems. As child problem behavior increased, parent psychological acceptance decreased, resulting in an increase in parent mental health problems. These findings suggest that for problems that are chronic and difficult to address, psychological acceptance may be an important factor in coping for parents of young people with ASD, in line with the growing literature on positive coping as compared with problem-focused coping. PMID- 22297203 TI - Assessing first year radiology resident competence pre-call: development and implementation of a computer-based exam before and after the 12 month training requirement. AB - RATIONALE AND OBJECTIVES: Whether first-year radiology residents are ready to start call after 6 or 12 months has been a subject of much debate. The purpose of this study was to establish an assessment that would evaluate the call readiness of first-year radiology residents and identify any individual areas of weakness using a comprehensive computerized format. Secondarily, we evaluated for any significant differences in performance before and after the change in precall training requirement from 6 to 12 months. MATERIALS AND METHODS: A list of >140 potential emergency radiology cases was given to first-year radiology residents at the beginning of the academic year. Over 4 years, three separate versions of a computerized examination were constructed using hyperlinked PowerPoint presentations and given to both first-year and second-year residents. No resident took the same version of the exam twice. Exam score and number of cases failed were assessed. Individual areas of weakness were identified and remediated with the residents. Statistical analysis was used to evaluate exam score and the number of cases failed, considering resident year and the three versions of the exam. RESULTS: Over 4 years, 17 of 19 (89%) first-year radiology residents passed the exam on first attempt. The two who failed were remediated and passed a different version of the exam 6 weeks later. Using the oral board scoring system, first-year radiology residents scored an average of 70.7 with 13 cases failed, compared to 71.1 with eight cases failed for second-year residents who scored statistically significantly higher. No significant difference was found in first year radiology resident scoring before and after the 12-month training requirement prior to call. CONCLUSIONS: An emergency radiology examination was established to aid in the assessment of first-year radiology residents' competency prior to starting call, which has become a permanent part of the first year curriculum. Over 4 years, all first-year residents were ultimately judged ready to start call. Of the variables assessed, only resident year showed a significant difference in scoring parameters. In particular, length of training prior to taking call showed no significant difference. Areas of weakness were identified for further study. PMID- 22297204 TI - Combining atlas-based parcellation of regional brain data acquired across scanners at 1.5 T and 3.0 T field strengths. AB - Longitudinal brain morphometric studies designed for data acquisition at a single MRI field strength can be seriously limited by system replacements from lower to higher field strength. Merging data across field strengths has not been endorsed for a variety of reasons, yet the ability to combine such data would broaden longitudinal investigations. To determine whether structural T1-weighted MRI data acquired across MR field strengths could be merged, parcellations of archival SPGR data acquired in 114 individuals at 1.5 T and at 3.0 T within 3 weeks of each other were compared. The first set of analyses examined 1) the correspondence between regional tissue volumes derived from data collected at 1.5 T and 3.0 T and 2) whether there were systematic differences for which a correction factor could be determined and applied to improve measurement agreement. Comparability of regional volume determination at 1.5 T and 3.0 T was assessed with intraclass correlation (ICC) computed on volumes derived from the automated and unsupervised SRI24 atlas registration and parcellation method. A second set of analyses measured the reliability of the registration and quantification using the same approach on longitudinal data acquired in 69 healthy adults at a single field strength, 1.5 T, at an interval < 2 years. The mainstay of the analyses was based on the SRI24 method; to examine the potential of merging data across field strengths and across image analysis packages, a secondary set of analyses used FreeSurfer instead of the SRI24 method. For both methods, a regression-based linear correction function significantly improved correspondence. The results indicated high correspondence between most selected cortical, subcortical, and CSF-filled spaces; correspondence was lowest in the globus pallidus, a region rich in iron, which in turn has a considerable field dependent effect on signal intensity. Thus, the application of a regression-based correction function that improved the correspondence in regional volume estimations argues well for the proposition that selected T1-weighted regional anatomical brain data can be reliably combined across 1.5 T and 3.0 T field strengths with the application of an appropriate correction procedure. PMID- 22297205 TI - BOLD fMRI investigation of the rat auditory pathway and tonotopic organization. AB - Rodents share general anatomical, physiological and behavioral features in the central auditory system with humans. In this study, monaural broadband noise and pure tone sounds are presented to normal rats and the resulting hemodynamic responses are measured with blood oxygenation level-dependent (BOLD) fMRI using a standard spin-echo echo planar imaging sequence (without sparse temporal sampling). The cochlear nucleus (CN), superior olivary complex, lateral lemniscus, inferior colliculus (IC), medial geniculate body and primary auditory cortex, all major auditory structures, are activated by broadband stimulation. The CN and IC BOLD signal changes increase monotonically with sound pressure level. Pure tone stimulation with three distinct frequencies (7, 20 and 40 kHz) reveals the tonotopic organization of the IC. The activated regions shift from dorsolateral to ventromedial IC with increasing frequency. These results agree with electrophysiology and immunohistochemistry findings, indicating the feasibility of auditory fMRI in rats. This is the first fMRI study of the rodent ascending auditory pathway. PMID- 22297206 TI - Preparation and biocompatibility of nanohybrid scaffolds by in situ homogeneous formation of nano hydroxyapatite from biopolymer polyelectrolyte complex for bone repair applications. AB - The achievement of nano distribution for inorganic reinforced filler is a big challenge to three-dimensional porous composite scaffolds. In this paper, a homogeneous nano hydroxyapatite/polyelectrolyte complex (HAP/PEC) hybrid scaffold was developed and investigated. Based on the enhancing properties of the formation of PEC between chitosan and hyaluronic acid, the introduction of nano HAP via in situ crystallization from the PEC achieved nano distribution in the PEC matrix and supplied nano topographies of extracellular environments for the nanohybrid scaffold. The biocompatibility and bioactivity were evaluated by Human bone mesenchymal stem cells (hBMSCs) proliferation (MTT assay), maturation (alkaline phosphatase (ALP) activity) and histological analysis. The in vitro tests show the scaffold is excellent for cell penetration, growth, and proliferation and it is promising for bone repair application. PMID- 22297207 TI - Beyond bevacizumab: antiangiogenic agents. AB - Angiogenesis is a rational target for the treatment of patients with non-small cell lung cancer (NSCLC). In the E4599 trial, the vascular endothelial growth factor (VEGF)-targeted antibody bevacizumab combined with carboplatin/paclitaxel improved both progression-free survival (PFS) and overall survival (OS) compared with chemotherapy alone. However responses to bevacizumab are usually transient and resistance inevitably develops. Thus other targets should be considered for future antiangiogenic strategies. A number of antiangiogenic agents with a variety of targets are in clinical development for NSCLC. Several multitargeted receptor tyrosine kinase inhibitors (TKIs) such as sorafenib, cediranib, and BIBF 1120, with activity against vascular endothelial growth factor receptor (VEGFR) and other proangiogenic pathways (eg, fibroblast growth factor [FGF] and platelet derived growth factor [PDGF] pathways) are in clinical development for NSCLC. Many of these TKIs have shown clinical activity in early trials, both alone and in combination with chemotherapy. Other promising agents in development include inhibitors of the angiopoietin/TIE2 pathway, integrin-targeted agents, vascular disrupting agents, and delta-like ligand-4/Notch pathway inhibitors. PMID- 22297208 TI - Single-heartbeat electromechanical wave imaging with optimal strain estimation using temporally unequispaced acquisition sequences. AB - Electromechanical Wave Imaging (EWI) is a non-invasive, ultrasound-based imaging method capable of mapping the electromechanical wave (EW) in vivo, i.e. the transient deformations occurring in response to the electrical activation of the heart. Optimal imaging frame rates, in terms of the elastographic signal-to noise ratio, to capture the EW cannot be achieved due to the limitations of conventional imaging sequences, in which the frame rate is low and tied to the imaging parameters. To achieve higher frame rates, EWI is typically performed by combining sectors acquired during separate heartbeats, which are then combined into a single view. However, the frame rates achieved remain potentially sub optimal and this approach precludes the study of non-periodic arrhythmias. This paper describes a temporally unequispaced acquisition sequence (TUAS) for which a wide range of frame rates are achievable independently of the imaging parameters, while maintaining a full view of the heart at high beam density. TUAS is first used to determine the optimal frame rate for EWI in a paced canine heart in vivo and then to image during ventricular fibrillation. These results indicate how EWI can be optimally performed within a single heartbeat, during free breathing and in real time, for both periodic and non-periodic cardiac events. PMID- 22297209 TI - Training children with ADHD to minimize impulsivity in auditory contralateral masking. AB - OBJECTIVE: Impulsivity and distractibility are among the important symptoms of attention deficit hyperactivity disorder (ADHD). In this study, impulsivity is operationally measured using false-alarm rates in an auditory, contralateral masking task. Intensive auditory training was attempted to decrease false alarm rates. METHODS: In contralateral masking there is a distracting noise in one ear on every trial and a threshold-level tone in the other ear on half of those trials. Participants indicated whether the tone was present or not and received immediate feedback. The intensity of the masked tone was adaptively varied to track threshold. False alarms are the error of commission, saying that a stimulus is present when it is not. Seven school-aged children with ADHD (ages 10-16) and four adults without ADHD were trained on this task for 900 trials per day over four consecutive days. RESULTS: False alarms from the children with ADHD decreased over the four days of training, beginning at the high level and ending at the low level expected from previous studies. There was no generalization to a different masking task. Results from the four adults were unexpected: soon after the training began they behaved no differently than the children with ADHD. CONCLUSION: Children with ADHD can be trained to become less impulsive in an auditory detection task. PMID- 22297210 TI - Circulating phospholipase-A2 activity in obstructive sleep apnea and recurrent tonsillitis. AB - OBJECTIVE: Phospholipase A2 (PLA2) plays a major part in growth regulation, differentiation and inflammation. It has been proposed as an evaluating marker for infection and inflammation. The aim of this study was to investigate activity of serum type II secretory PLA2 (sPLA2 IIa) in obstructive sleep apnea (OSA) and recurrent infective tonsillitis (RT) in children. METHODS: Activity of serum sPLA2 IIa was determined in children who underwent tonsillectomy, including OSA in 126 cases and RT in 60. Serum enzyme activities were measured using the standard assay with Diheptanoyl Thio-Phosphatidylcholin as substrate. RESULTS: The sPLA2 IIa activity of serum was significantly higher in RT than in OSA (P<0.01). Serum sPLA2 IIa activity in the RT patients was positively correlated with BMI (r=0.26; P=0.02), which was not apparent in OSA (r=0.14; P=0.09). CONCLUSION: This study suggests that serum sPLA2 IIa activity may be considered as a supportive diagnostic marker in suspected or clinically unclear cases of RT children. PMID- 22297211 TI - Neck tumour - lung hernia in a 10-year-old girl - diagnostic difficulties. AB - Spontaneous hernias of the pleural cupola are extremely rare tumours in the neck area. The most common tumours in children are lymph node abnormalities, and cysts that are remnants of the branchial arches. Due to diagnostic and therapeutic difficulties, we would like to present the case of a 10-year-old girl, with a neck tumour that was observed during coughing and was accompanied by dyspnea. The girl was admitted to the Paediatric Hospital of Warsaw Medical University. Finally, the neck tumour was diagnosed as a hernia of the pleural cupola, which was subsequently treated surgically. In a review of the literature we found two case reports of similar disorders that appeared spontaneously. All cases of neck tumours in children require very precise radiological diagnostic investigation. Spontaneous lung hernia is an extremely rare cause of neck tumours, which is treated surgically if it becomes symptomatic. PMID- 22297212 TI - Minocycline reduces articular cartilage damage following osteochondral injury. AB - INTRODUCTION: Secondary injury pathways activated after chondral and osteochondral injury represent a potential target for therapies designed to minimize articular cartilage loss. The primary objective of this study was to test the potential chondroprotective effects of intra-articular minocycline following osteochondral injury. METHODS: In vitro experiments were first performed with rabbit femoral condyles explants using an osteochondral drill injury model. Data from these in vitro experiments showed that minocycline at concentrations of 10-1000 nM decreased chondrocyte apoptosis in a dose-dependent manner. In vivo experiments were then conducted using the same injury model, studying the effects of intra-articular minocycline on chondrocyte apoptosis, chondrocyte cell number, and cartilage thickness. RESULTS: Four days after injury, minocycline delivered daily directly into the rabbit knee joints decreased acute chondrocyte apoptosis by 56% compared to controls. Analysis performed six weeks after injury demonstrated superior chondrocyte cell number, cartilage thickness, and cartilage repair in animals receiving short-term (one week) minocycline treatment compared to controls. CONCLUSIONS: These data support a therapeutic approach utilizing drugs like minocycline for the acute treatment of osteochondral injuries. PMID- 22297213 TI - An audit of the cervical cancer screening histories of 246 women with carcinoma. AB - OBJECTIVE: Women with cervical carcinoma and residing in the Calgary Health Region between 1996 and 2001 were audited to characterize factors in the opportunistic cervical cancer screening pathway contributing to screening failures. MATERIALS AND METHODS: The cohort consisted of 246 women. Information on their Pap tests and colposcopic/gynecologic examinations was obtained from the files of Calgary Laboratory Services and their colposcopic/cancer center treatment charts. Screening failure factors were defined, and frequencies were calculated. RESULTS: Screening failure factors were as follows: (1) 41 (16.7%) were not screened, that is, no Pap test screening; (2) 29 (11.8%) were underscreened, that is, no Pap test within 12 months of diagnosis; (3) 28 (13.7%) were undersampled, that is, the Pap test result was negative; (4) 34 (13.8%) had no referral for a colposcopy/gynecology examination, and/or it was delayed for more than 3 months; (5) 18 (13.2%) had delayed referral for examination of an atypical glandular cell-high-grade squamous intraepithelial lesion and higher Pap test for more than 3 months; and (6) 73 (55.3%) were underdiagnosed, that is, the diagnosis in colposcopy examination was less than malignant. Underreported Pap tests and delayed Pap test reporting could not be fully investigated, but limited evidence suggested that underreporting contributed to some failures. CONCLUSIONS: Factors other than recruitment to cytological screening need targeted improvement if the region's cervical cancer prevention program is to be more effective. PMID- 22297214 TI - Cyanobacterial diversity shifts induced by butachlor in selected Indian rice fields in Eastern Uttar Pradesh and Western Bihar analyzed with PCR and DGGE. AB - The present study examines the effects of 30 mg/kg butachlor on the cyanobacterial diversity of rice fields in Eastern Uttar Pradesh and Western Bihar in India. A total of 40 samples were grouped into three classes [(i) acidic, (ii) neutral, and (iii) alkaline soils], based on physicochemical and principle component analyses. Acidic soils mainly harbored Westillopsis, Trichormus, Anabaenopsis, and unicellular cyanobacteria; whereas Nostoc, Anabaena, Calothrix, Tolypothrix, and Aulosira were found in neutral and alkaline soils. Molecular characterization using 16S rRNA PCR and DGGE revealed the presence of 13 different phylotypes of cyanobacteria in these samples. Butachlor treatment of the soil samples led to the disappearance of 5 and the emergence of 2 additional phylotypes. A total of 40 DGGE bands showed significant reproducible changes upon treatment with butachlor. Phylogenetic analyses divided the phylotypes into five major clusters exhibiting interesting links with soil pH. Aulosira, Anabaena, Trichormus, and Anabaenopsis were sensitive to butachlor treatment, whereas uncultured cyanobacteria, a chroococcalean member, Westillopsis, Nostoc, Calothrix, Tolypothrix, Rivularia, Gloeotrichia, Fischerella, Leptolyngbya, and Cylindrospermum, appeared to be tolerant against butachlor at their native soil pH. Butachlor-induced inhibition of nitrogen fixation was found to be 65% (maximum) and 33% (minimum) in the soil samples of pH 9.23 and 5.20, respectively. In conclusion, low butachlor doses may prove beneficial in paddy fields having a neutral to alkaline soil pH. PMID- 22297215 TI - Genotypic and phenotypic diversity of PGPR fluorescent pseudomonads isolated from the rhizosphere of sugarcane (Saccharum officinarum L.). AB - The genetic diversity of plant growth-promoting rhizobacterial (PGPR) fluorescent pseudomonads associated with the sugarcane (Saccharum officinarum L.) rhizosphere was analyzed. Selected isolates were screened for plant growthpromoting properties including production of indole acetic acid, phosphate solubilization, denitrification ability, and production of antifungal metabolites. Furthermore, 16S rDNA sequence analysis was performed to identify and differentiate these isolates. Based on 16S rDNA sequence similarity, the isolates were designated as Pseudomonas plecoglossicida, P. fluorescens, P. libaniensis, and P. aeruginosa. Differentiation of isolates belonging to the same group was achieved through different genomic DNA fingerprinting techniques, including randomly amplified polymorphic DNA (RAPD), amplified ribosomal DNA restriction analysis (ARDRA), repetitive extragenic palindromic (REP), enterobacterial repetitive intergenic consensus (ERIC), and bacterial repetitive BOX elements (BOX) analyses. The genetic diversity observed among the isolates and rep-PCR-generated fingerprinting patterns revealed that PGPR fluorescent pseudomonads are associated with the rhizosphere of sugarcane and that P. plecoglossicida is a dominant species. The knowledge obtained herein regarding the genetic and functional diversity of fluorescent pseudomonads associated with the sugarcane rhizosphere is useful for understanding their ecological role and potential utilization in sustainable agriculture. PMID- 22297216 TI - Virulence, resistance genes, and transformation amongst environmental isolates of Escherichia coli and Acinetobacter spp. AB - The association of verotoxic E. coli and Acinetobacter spp. with various antibiotic-resistant, diarrhogenic, and nosocomial infections has been a cause for concern worldwide. E. coli and A. haemolyticus isolated on a number of selective media were screened for virulence factors, antibiotic resistance, and transformation of resistance genes. Out of 69 E. coli isolates obtained, 25 (35.23%), 14 (20.30%), and 28 (40.58%) were positive for Vtx1&2, Vtx1, and Vtx2, respectively, 49 (71.015%) for extendedspectrum beta-lactamases (ESBLs), 34 (49.28%) for serum resistance, 57 (82.61%) for cell surface hydrophobicity, 48 (69.57%) for gelatinase production, and 37 (53.62%) for hemolysin production. For the 14 A. haemolyticus isolates, only 2 (14.29%) in each case from all the samples investigated were positive for Vtx1, Vtx2 and Vtx1&2 respectively, 8 (57.14%) for ESBLs, 7 (50.00%) for serum resistance, 11 (78.57%) for cell surface hydrophobicity, 4 (28.57%) for gelatinase production, and 8 (57.14%) for hemolysin production. Although transformation occurred among the E. coli and Acinetobacter isolates (transformation frequency: 13.3 * 10(-7) -53.4(-7)), there was poor curing of the plasmid genes, a confirmation of the presence of stable antibiotic-resistant genes (DNA concentration between 42.7 and 123.8 microgram) and intragenetic transfer of multidrugresistant genes among the isolates. The isolates were potentially virulent and contained potentially transferable antibiotic resistance genes. Detection of virulence factors, antibiotic resistance genes, and transformation among these isolates is a very significant outcome that will influence approaches to proactive preventive and control measures and future investigations. However, continued surveillance for drug resistance among these bacteria and further investigation of the mechanism of action of their virulence factors are a necessity. PMID- 22297217 TI - Effect of ion pair on thermostability of F1 protease: integration of computational and experimental approaches. AB - A thermophilic Bacillus stearothermophilus F1 produces an extremely thermostable serine protease. The F1 protease sequence was used to predict its three dimensional (3D) structure to provide better insights into the relationship between the protein structure and biological function and to identify opportunities for protein engineering. The final model was evaluated to ensure its accuracy using three independent methods: Procheck, Verify3D, and Errat. The predicted 3D structure of F1 protease was compared with the crystal structure of serine proteases from mesophilic bacteria and archaea, and led to the identification of features that were related to protein stabilization. Higher thermostability correlated with an increased number of residues that were involved in ion pairs or networks of ion pairs. Therefore, the mutants W200R and D58S were designed using site-directed mutagenesis to investigate F1 protease stability. The effects of addition and disruption of ion pair networks on the activity and various stabilities of mutant F1 proteases were compared with those of the wild-type F1 protease. PMID- 22297218 TI - Identification of the fur-binding site in regulatory region of the vulnibactin receptor gene in Vibrio vulnificus. AB - The Vibrio vulnificus vuuA gene, of which expression is repressed by a complex of iron and ferric uptake regulator (Fur), was characterized to localize the Fur binding site in its upstream regulatory region. In silico analysis suggested the presence of two possible Fur-binding sites; one is a classical Fur-box and the other is a previously reported distinct Fur-binding site. Site-directed mutagenesis and DNase I protection assays revealed the binding site for the iron Fur complex, which includes an extended inverted repeat containing a homologous sequence to the classical Fur-box. PMID- 22297219 TI - Cells transformed by PLC-gamma 1 overexpression are highly sensitive to clostridium difficile toxin A-induced apoptosis and mitotic inhibition. AB - Phospholipase C-gammal (PLC-gammal) expression is associated with cellular transformation. Notably, PLC-gamma is up-regulated in colorectal cancer tissue and breast carcinoma. Because exotoxins released by Clostridium botulinum have been shown to induce apoptosis and promote growth arrest in various cancer cell lines, we examined here the potential of Clostridium difficile toxin A to selectively induce apoptosis in cells transformed by PLC-gammal overexpression. We found that PLC-gammal-transformed cells, but not vectortransformed (control) cells, were highly sensitive to C. difficile toxin A-induced apoptosis and mitotic inhibition. Moreover, expression of the proapoptotic Bcl2 family member, Bim, and activation of caspase-3 were significantly up-regulated by toxin A in PLC-gammal-transformed cells. Toxin A-induced cell rounding and paxillin dephosphorylation were also significantly higher in PLC-gammal-transformed cells than in control cells. These findings suggest that C. difficile toxin A may have potential as an anticancer agent against colorectal cancers and breast carcinomas in which PLC-gammal is highly up-regulated. PMID- 22297220 TI - Purification and characterization of a novel alkaline protease from Bacillus horikoshii. AB - An investigation was conducted on the enhancement of production and purification of an oxidant and SDS-stable alkaline protease (BHAP) secreted by an alkalophilic Bacillus horikoshii, which was screened from the body fluid of a unique Korean polychaeta (Periserrula leucophryna) living in the tidal mud flats of Kwangwha Island in the Korean West Sea. A prominent effect on BHAP production was obtained by adding 2% maltose, 1% sodium citrate, 0.8% NaCl, and 0.6% sodium carbonate to the culturing medium. The optimal medium for BHAP production contained (g/l) SBM, 15; casein, 10; K(2)HPO(4), 2; KH(2)PO(4), 2; maltose, 20; sodium citrate, 10; MgSO(4), 0.06; NaCl, 8; and Na(2)CO(3), 6. A protease yield of approximately 56,000 U/ml was achieved using the optimized medium, which is an increase of approximately 5.5-fold compared with the previous optimization (10,050 U/ml). The BHAP was homogenously purified 34-fold with an overall recovery of 34% and a specific activity of 223,090 U/mg protein using adsorption with Diaion HPA75, hydrophobic interaction chromatography (HIC) on Phenyl-Sepharose, and ion exchange chromatography on a DEAE- and CMSepharose column. The purified BHAP was determined a homogeneous by SDS-PAGE, with an apparent molecular mass of 28 kDa, and it showed extreme stability towards organic solvents, SDS, and oxidizing agents. The K(m) and k(cat) values were 78.7 MUM and 217.4 s(-1) for N-succinyl Ala- Ala-Pro-Phe-pNA at 37 degrees C and pH 9, respectively. The inhibition profile exhibited by PMSF suggested that the protease from B. horikoshii belongs to the family of serine proteases. The BHAP, which showed high stability against SDS and H(2)O(2), has significance for industrial application, such as additives in detergent and feed industries. PMID- 22297221 TI - Metabolic profiling and biological activities of bioactive compounds produced by Pseudomonas sp. strain ICTB-745 isolated from Ladakh, India. AB - In an ongoing survey of the bioactive potential of microorganisms from Ladakh, India, the culture medium of a bacterial strain of a new Pseudomonas sp., strain ICTB-745, isolated from an alkaline soil sample collected from Leh, Ladakh, India, was found to contain metabolites that exhibited broad-spectrum antimicrobial and biosurfactant activities. Bioactivity-guided purification resulted in the isolation of four bioactive compounds. Their chemical structures were elucidated by (1)H and (13)C NMR, 2D-NMR (HMBC, HSQC, (1)H,(1)H-COSY, and DEPT- 135), FT-IR, and mass spectroscopic methods, and were identified as 1 hydroxyphenazine, phenazine-1-carboxylic acid (PCA), rhamnolipid-1 (RL-1), and rhamnolipid-2 (RL-2). These metabolites exhibited various biological activities like antimicrobial and efficient cytotoxic potencies against different human tumor cell lines such as HeLa, HepG2, A549, and MDA MB 231. RL-1 and RL-2 exhibited a dose-dependent antifeedant activity against Spodoptera litura, producing about 82.06% and 73.66% antifeedant activity, whereas PCA showed a moderate antifeedant activity (63.67%) at 60 microgram/cm2 area of castor leaf. Furthermore, PCA, RL-1, and RL-2 exhibited about 65%, 52%, and 47% mortality, respectively, against Rhyzopertha dominica at 20 microgram/ml. This is the first report of rhamnolipids as antifeedant metabolites against Spodoptera litura and as insecticidal metabolites against Rhyzopertha dominica. The metabolites from Pseudomonas sp. strain ICTB-745 have interesting potential for use as a biopesticide in pest control programs. PMID- 22297222 TI - New production of 5-bromotoluhydroquinone and 4-O-methyltoluhydroquinone from the marine-derived fungus Dothideomycete sp. AB - The addition of NaBr to the fermentation medium of a marine isolate of the fungus Dothideomycete sp. resulted in induced production of two toluhydroquinone derivatives, 5- bromotoluhydroquinone (1) and 4-O-methyltoluhydroquinone (2), and two known compounds, toluhydroquinone (3) and gentisyl alcohol (4). The structures of 1 and 2 were assigned through the spectroscopic data analyses. Compounds 1-4 showed a potent antibacterial activity against the methicillinresistant and multidrug-resistant Staphylococcus aureus (MRSA and MDRSA) with MIC (minimum inhibitory concentration) values of 6.2, 12.5, 6.2, and 12.5 microgram/ml, respectively. Compounds 1-4 also exhibited a moderate radical scavenging activity against 1,1-diphenyl-2- picrylhydrazyl (DPPH) with IC(50) values of 11.0, 17.0, 12.0, and 7.0 microM, respectively, which were more active than the positive control, L-ascorbic acid (IC(50), 20.0 MUM). PMID- 22297223 TI - Characterization of lipases from Staphylococcus aureus and Staphylococcus epidermidis isolated from human facial sebaceous skin. AB - Two staphylococcal lipases were obtained from Staphylococcus epidermidis S2 and Staphylococcus aureus S11 isolated from sebaceous areas on the skin of the human face. The molecular mass of both enzymes was estimated to be 45 kDa by SDS-PAGE. S2 lipase displayed its highest activity in the hydrolysis of olive oil at 32 degrees C and pH 8, whereas S11 lipase showed optimal activity at 31 degrees C and pH 8.5. The S2 lipase showed the property of cold-adaptation, with activation energy of 6.52 kcal/mol. In contrast, S11 lipase's activation energy, at 21 kcal/mol, was more characteristic of mesophilic lipases. S2 lipase was stable up to 45 degrees C and within the pH range from 5 to 9, whereas S11 lipase was stable up to 50 degrees C and from pH 6 to 10. Both enzymes had high activity against tributyrin, waste soybean oil, and fish oil. Sequence analysis of the S2 lipase gene showed an open reading frame of 2,067 bp encoding a signal peptide (35 aa), a pro-peptide (267 aa), and a mature enzyme (386 aa); the S11 lipase gene, at 2,076 bp, also encoded a signal peptide (37 aa), pro-peptide (255 aa), and mature enzyme (399 aa). The two enzymes maintained amino acid sequence identity of 98-99% with other similar staphylococcal lipases. Their microbial origins and biochemical properties may make these staphylococcal lipases isolated from facial sebaceous skin suitable for use as catalysts in the cosmetic, medicinal, food, or detergent industries. PMID- 22297224 TI - Poly(L-lactide)-degrading enzyme production by Actinomadura keratinilytica T16-1 in 3 L airlift bioreactor and its degradation ability for biological recycle. AB - The optimal physical factors affecting enzyme production in an airlift fermenter have not been studied so far. Therefore, the physical parameters such as aeration rate, pH, and temperature affecting PLA-degrading enzyme production by Actinomadura keratinilytica strain T16-1 in a 3 l airlift fermenter were investigated. The response surface methodology (RSM) was used to optimize PLA degrading enzyme production by implementing the central composite design. The optimal conditions for higher production of PLA-degrading enzyme were aeration rate of 0.43 vvm, pH of 6.85, and temperature at 46 degrees C. Under these conditions, the model predicted a PLA-degrading activity of 254 U/ml. Verification of the optimization showed that PLA-degrading enzyme production of 257 U/ml was observed after 3 days cultivation under the optimal conditions in a 3 l airlift fermenter. The production under the optimized condition in the airlift fermenter was higher than un-optimized condition by 1.7 folds and 12 folds with un-optimized medium or condition in shake flasks. This is the first report on the optimization of environmental conditions for improvement of PLA degrading enzyme production in a 3 l airlift fermenter by using a statistical analysis method. Moreover, the crude PLA-degrading enzyme could be adsorbed to the substrate and degraded PLA powder to produce lactic acid as degradation products. Therefore, this incident indicates that PLA-degrading enzyme produced by Actinomadura keratinilytica NBRC 104111 strain T16-1 has a potential to degrade PLA to lactic acid as a monomer and can be used for the recycle of PLA polymer. PMID- 22297225 TI - Metabolite profiling and bioactivity of rice koji fermented by Aspergillus strains. AB - In this study, the metabolite profiles of three Aspergillus strains during rice koji fermentation were compared. In the partial least squares discriminant analysis-based gas chromatography-mass spectrometry data sets, the metabolite patterns of A. oryzae (KCCM 60345) were clearly distinguished from A. kawachii (KCCM 60552) and only marginal differences were observed for A. oryzae (KCCM 60551) fermentation. In the 2 days fermentation samples, the overall metabolite levels of A. oryzae (KCCM 60345) were similar to the A. oryzae (KCCM 60551) levels and lower than the A. kawachii (KCCM 60552) levels. In addition, we identified discriminators that were mainly contributing tyrosinase inhibition (kojic acid) and antioxidant activities (pyranonigrin A) in A. oryzae (KCCM 60345) and A. kawachii (KCCM 60552) inoculated rice koji, respectively. In this study, we demonstrated that the optimal inoculant Aspergillus strains and fermentation time for functional rice koji could be determined through a metabolomics approach with bioactivity correlations. PMID- 22297226 TI - Development of a practical and cost-effective medium for bioethanol production from the seaweed hydrolysate in surface-aerated fermentor by repeated-batch operation. AB - To develop a practical and cost-effective medium for bioethanol production from the hydrolysate of seaweed Sargassum sagamianum, we investigated the feasibility and performance of bioethanol production in CSL (cornsteep liquor)-containing medium, where yeast Pichia stipitis was used and the repeated batch was carried out in a surface-aerated fermentor. The optimal medium replacement time during the repeated operation was determined to be 36 h, and the surface aeration rates were 30 and 100 ml/min. Under these conditions, the repeatedbatch operation was successfully carried out for 6 runs (216 h), in which the maximum bioethanol concentrations reached about 11-12 g/l at each batch operation. These results demonstrated that bioethanol production could be carried out repeatedly and steadily for 216 h. In these experiments, the total cumulative bioethanol production was 57.9 g and 58.0 g when the surface aeration rates were 30 ml/min and 100 ml/min, respectively. In addition, the bioethanol yields were 0.43 (about 84% of theoretical value) and 0.44 (about 86% of theoretical value) when the surface aeration rates were 30 ml/min and 100 ml/min, respectively. CSL was successfully used as a medium ingredient for the bioethanol production from the hydrolysate of seaweed Sargassum sagamianum, indicating that this medium may be practical and cost-effective for bioethanol production. PMID- 22297227 TI - Bacterial mixture from greenhouse soil as a biocontrol agent against root-knot nematode, Meloidogyne incognita, on oriental melon. AB - The biological control efficacy of a greenhouse soil bacterial mixture of Lactobacillus farraginis, Bacillus cereus, and Bacillus thuringiensis strains with antinematode activity was evaluated against the root-knot nematode Meloidogyne incognita. Two control groups planted in soil drenched with sterile distilled water or treated with the broadspectrum carbamate pesticide carbofuran were used for comparison. The results suggest that the bacterial mixture is effective as a biocontrol agent against the root-knot nematode. PMID- 22297228 TI - HspA and HtpG enhance thermotolerance in the cyanobacterium, Microcystis aeruginosa NIES-298. AB - Heat shock proteins (Hsps) play a key role in the cellular defense response to diverse environmental stresses. Here, the role of Hsp genes in the acquisition of thermotolerance in the cyanobacterium Microcystis aeruginosa NIES-298 was investigated. Twelve Hsp-related genes were examined to observe their modulated expression patterns at different temperatures (10, 15, 25, and 35 degrees C) over different exposure periods. HspA and HtpG transcripts showed an up regulation of expression at low temperatures (10 and 15 degrees C) and high temperature (35 degrees C), compared with the control (25 degrees C). To examine their effects upon thermotolerance, we purified recombinant HspA and HtpG proteins. During a thermotolerance study at 54 degrees C, the HspA-transformed bacteria showed increased thermotolerance compared with the control. HtpG also played a role in the defense response to acute heat stress within 30 min. These findings provide a better understanding of cellular protection mechanisms against heat stress in cyanobacteria. PMID- 22297229 TI - Survival and performance of two cellulose-degrading microbial systems inoculated into wheat straw-amended soil. AB - A cellulose-degrading composite microbial system containing a mixture of microbes was previously shown to demonstrate a high straw-degrading capacity. To estimate its potential utilization as an inoculant to accelerate straw biodegradation after returning straw to the field, two cellulose-degrading composite microbial systems named ADS3 and WSD5 were inoculated into wheat straw-amended soil in the laboratory. The microbial survival of the inoculant was confirmed by a denaturing gradient gel electrophoresis (DGGE) analysis, whereas the enhancement of straw degradation in soil was assessed by measuring the mineralization of the soil organic matter and the soil cellulase activity. The results indicated that most of the DGGE bands from ADS3 were detected after inoculation into straw-amended autoclaved soil, yet only certain bands from ADS3 and WSD5 were detected after inoculation into straw-amended non-autoclaved soil during five weeks of incubation; some bands were detected during the first two weeks after inoculation, and then disappeared in later stages. Organic matter mineralization was significantly higher in the soil inoculants ADS3 and WSD5 than in the uninoculated controls during the first week, yet the enhanced degradation did not persist during the subsequent incubation. Similar to the increase in soil organic matter, the cellulase activity also increased during the first week in the ADS3 and WSD5 treatments, yet decreased during the remainder of the incubation period. Thus, it was concluded that, although the survival and performance of the two inoculants did not persist in the soil, a significant enhancement of degradation was present during the early stage of incubation. PMID- 22297230 TI - A novel cry2Ab gene from the indigenous isolate Bacillus thuringiensis subsp. kurstaki. AB - A novel cry2Ab gene was cloned and sequenced from the indigenous isolate of Bacillus thuringiensis subsp. kurstaki. This gene was designated as cry2Ab25 and its sequence revealed an open reading frame of 1,902 bp encoding a 633 aa protein with calculated molecular mass of 70 kDa and pI value of 8.98. The amino acid sequence of the Cry2Ab25 protein was compared with previously known Cry2Ab toxins, and the phylogenetic relationships among them were determined. The deduced amino acid sequence of the Cry2Ab25 protein showed 99% homology to the known Cry2Ab proteins, except for Cry2Ab10 and Cry2Ab12 with 97% homology, and a variation in one amino acid residue in comparison with all known Cry2Ab proteins. The cry2Ab25 gene was expressed in Escherichia coli BL21(DE3) cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed that the Cry2Ab25 protein is about 70 kDa. The toxin expressed in BL21(DE3) exhibited high toxicity against Malacosoma neustria and Rhagoletis cerasi with 73% and 75% mortality after 5 days of treatment, respectively. PMID- 22297231 TI - Functional expression and characterization of recombinant NADPH-P450 reductase from Malassezia globosa. AB - Malassezia globosa is a common pathogenic fungus that causes skin diseases including dandruff and seborrheic dermatitis in humans. Analysis of its genome identified a gene (MGL_1677) coding for a putative NADPH-P450 reductase (NPR) to support the fungal cytochrome P450 enzymes. The heterologously expressed recombinant M. globosa NPR protein was purified, and its functional features were characterized. The purified protein generated a single band on SDS-PAGE at 80.74 kDa and had an absorption maximum at 452 nm, indicating its possible function as an oxidized flavin cofactor. It evidenced NADPH-dependent reducing activity for cytochrome c or nitroblue tetrazolium. Human P450 1A2 and 2A6 were able to successfully catalyze the O-deethylation of 7- ethoxyresorufin and the 7 hydroxylation of coumarin, respectively, with the support of the purified NPR. These results demonstrate that purified NPR is an orthologous reductase protein that supports cytochrome P450 enzymes in M. globosa. PMID- 22297232 TI - Synergic effects of bitter melon and beta-Glucan composition on STZ-induced rat diabetes and its complications. AB - beta-Glucan purified from oats (OG) and bitter melon, Momordica charantia Linn (MC), water extracts have shown favorable effects on diabetes and its complications. We investigated to find out the optimal composition showing hypoglycemic and antidiabetic complication effects in variable compositions (OG:MC = 1:1, 1:2, 1:4, 1:6, 1:8, 1:10, 2:1, 4:1, 6:1, 8:1, 10:1). Extracts were administered orally once a day for 28 days following 7 days post streptozotocin (STZ) dosing. Five rats per group (total 15 groups; Intact, STZ, OG, MC, and the variable composition groups) were selected according to the blood glucose and body weight at 6 days after STZ dosing. After 28 days of extracts dosing, the changes on the body weight, liver and kidney weight, blood glucose, blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), low-density lipoprotein (LDL), and total-cholesterol levels were observed. As the result of STZ-induced diabetes, decreases of body weight, increases of the liver and kidney weights, blood glucose, BUN, creatinine, AST, ALT, LDL, and total-cholesterol levels in STZ control were detected compared with intact control. However, these changes of hyperglycemia, diabetic nephropathy, hepatopathy, and hyperlipemia were dramatically decreased in the OG and MC single-dosing group, and all composition groups. In addition, there were more favorable effects in all composition groups compared with the OG and MC single-dosing groups. Among variable compositions, the OG:MC 1:2 mixed group showed the most synergic effects in this study. PMID- 22297233 TI - Effects of the synthetic coprisin analog peptide, CopA3 in pathogenic microorganisms and mammalian cancer cells. AB - A synthetic coprisin analog peptide, 9-mer dimer CopA3 (CopA3) was designed based on a defensin-like peptide, Coprisin, isolated from the bacteria-immunized dung beetle Copris tripartitus. Here, CopA3 was investigated for its antimicrobial activity and cancer cell growth inhibition. CopA3 showed antimicrobial activities against various pathogenic bacteria and yeast fungus with MIC values in 2~32 MUM ranges, and inhibited the cell viabilities of pancreatic and hepatocellular cancer cells, except MIAPaca2, Hep3B, and HepG2 cells, in a dose-dependent manner. The average IC(50) values of CopA3 against pancreatic and hepatocellular cancer cells were 61.7 MUM and 67.8 MUM, respectively. The results indicate that CopA3 has potential in the treatments of pancreatic and hepatocellular cancers as well as microorganism infection disease. PMID- 22297234 TI - Essential roles of insulin expression in Aire+ tolerogenic dendritic cells in maintaining peripheral self-tolerance of islet beta-cells. AB - Anti-insulin autoimmunity is one of the primary forces in initiating and progressing beta-cell destruction in type 1 diabetes. While insulin expression in thymic medullary epithelial cells has been shown to be essential for establishing beta-cell central tolerance, the function of insulin expression in antigen presenting cells (APCs) of hematopoietic lineage remains elusive. With a Cre-lox reporter approach, we labeled Aire-expressing cells with enhanced yellow fluorescent proteins, and found that insulin expression in the spleen was restricted predominantly to a population of Aire(+)CD11c(int)B220(+) dendritic cells (DCs). Targeted insulin deletion in APCs failed to induce anti-islet autoimmunity in B6 mice. In contrast, elevated levels of T cell infiltration into islets were observed in B6(g7) congenic mice when insulin was specifically deleted in their CD11c-expressing DCs (B6(g7).CD11c-DeltaIns mice). Thus, insulin expression in BM-derived, Aire(+) tolerogenic DCs may play an essential role to prevent the activation and expansion of insulin-reactive T cells in the periphery. PMID- 22297235 TI - The SSRIs: advantages, disadvantages and differences. AB - The highly specific mechanism of action of the selective serotonin re-uptake inhibitors (SSRIs) confers advantages on this group, relative to other classes of antidepressant, and thus represents a significant advance in the pharmacotherapy of depression. Whilst their clinical efficacy is equivalent to that of the tricyclic antidepressants (TCAs), the SSRIs have a greatly reduced risk of toxicity in overdose and have been shown to be significantly better tolerated. Specifically, the SSRIs have a low incidence of anticholinergic effects and are essentially devoid of cardiotoxicity. This tolerability advantage may be of significance in improving compliance and hence cost-effectiveness of treatment, particularly in the long term. Despite a lack of sedative effect, there is evidence that SSRIs are more effective than TCAs in the treatment of depression with anxiety. In addition, the SSRIs have been shown to be effective in obsessive compulsive disorder, panic disorder and social phobia. Although superior efficacy has not been demonstrated for any one of the SSRIs, the structural diversity of this group is reflected in emerging qualitative and quantitative differences in side effects and drug interaction potential. Many of these differential features reflect important variations in pharmacological and pharmacokinetic profiles, including dosage flexibility, washout times, dose-plasma level proportionality and age-related changes in plasma levels. Fluoxetine, for example, has a considerably longer half-life than other SSRIs and side effects and drug interactions may thus occur for an extended period following discontinuation of treatment. Significant differences in the potential for drug interactions in this group are related to their relative potency for inhibition of important liver drug-metabolising enzymes including CYPIID6, CYPIA2 and CYPIIIA4. Large comparative clinical trials of the different SSRIs have yet to be undertaken; however, the differences that have already become apparent provide important information enabling the physician to choose an SSRI appropriate to the individual patient. PMID- 22297236 TI - Serotonin, sertraline and depression. AB - Sertraline is a highly selective serotonin re-uptake inhibitor (SSRI) whose efficacy in depression has been established in a number of large placebo controlled studies in patients with moderate to severe major depressive episodes (DSM-III). This antidepressant efficacy appears to be significantly more effective than placebo and imipramine and at least of the same order as that of the reference tricyclic antidepressants (TCAs) amitriptyline, clomipramine and dothiepin. More recently, two double-blind parallel group studies have demonstrated comparable efficacy to another SSRI, fluoxetine. Sertraline has demonstrated efficacy in the long-term maintenance and prophylaxis of depression and is one of the few SSRIs currently indicated for the prevention of relapse and recurrence of depression. Fixed dose studies have confirmed the efficacy and optimal tolerability of the minimum 50 mg dose. The efficacy of sertraline, demonstrated across a broad spectrum of depression, and its consistently improved tolerability and safety profile over the TCAs, confirm its potential as a first- line treatment for acute and recurrent episodes of depression. PMID- 22297237 TI - The anxiety factor in depression. AB - Anxiety symptoms are commonly associated with depression, and contribute to a poorer patient prognosis. An increase in serotonergic function is implicated in the pathogenesis of anxiety and there is good evidence that the selective serotonin re-uptake inhibitors (SSRIs) may be useful in clinical management. Sertraline, a novel SSRI, has been shown to be effective in the treatment of anxiety symptoms in both pure and mixed anxiety disorders. Studies have also shown sertraline to be effective in obsessive-compulsive disorder. A recent study (Moon et al. , 1994) shows sertraline to have comparative therapeutic efficacy with that of clomipramine with respect to reduction of anxiety symptoms in depression. However, it also highlights important differences in side-effect profiles, with a high incidence of cardiovascular effects and subsequent dropouts reported in the clomipramine group. Limited comparative data with other SSRIs suggest there is no evidence of any aggravation of anxiety symptoms during treatment with sertraline, as has been reported with fluoxetine. Sertraline has been shown to have a normalising effect on sleep disturbance in depression without evidence of daytime sedation. Therefore, given the high prevalence of anxiety symptoms in depression, sertraline would be a useful therapeutic option in clinical management. PMID- 22297238 TI - The long-term management of depression. AB - The long-term outlook for patients with unipolar depression is often poor. As few as one-fifth will remain well and a similar number will suffer chronic depression. It is now standard practice to extend acute treatment into a 4-6 month period of continuation therapy, and the value of prophylactic treatment over longer periods is becoming more widely recognised. Care must, however, be exercised in choosing suitable long-term treatment. Relatively little work on the prophylactic efficacy of the tricyclic antidepressants has been carried out, although imipramine has been shown to be effective. The selective serotonin re uptake inhibitors (SSRIs) have been studied extensively and may be the most suitable long-term treatment for depression. Sertraline is effective in preventing both relapse and recurrence of depression and was the first agent specifically indicated for the long-term treatment of depression in the UK. In addition to clinical efficacy, many other factors favour SSRIs in the long-term management of depression. The tolerability of a drug is of major importance in long-term therapy since it affects compliance. Other important considerations include toxicity, safety in overdose, drug interaction potential, psychomotor effects and accident liability. PMID- 22297239 TI - Treatment approaches to therapy-resistant depression. AB - Resistance to antidepressant treatment is a controversial field and therapy resistance has received a wide range of definitions. The field has suffered from a lack of consensus on how to classify treatment resistance and from the related failure to standardise clinical criteria in trials of new therapeutic approaches. A significant proportion of tricyclic antidepressant (TCA)-resistant depression results from the failure to sustain an adequate course of therapy. This can be due to either inadequate prescribing or the poor tolerability of TCAs. The majority of cases of treatment resistance, however, involve antidepressant therapy at a dose and duration that would normally be expected to be effective. In these cases, therapy may fail for many reasons. Refractory depression may occur in patients with medical conditions such as subclinical hypothyroidism, stroke and closed head injuries. Patients with alcoholism may prove refractory to treatment, as may those receiving certain medications, notably calcium channel blockers. Certain subtypes of depression, such as rapid-cycling disorder and delusional depression, also appear to be more refractory to treatment. A variety of therapeutic approaches have been applied to treatment-resistant depression but, for most of these, placebo-controlled clinical trials with substantial numbers of patients have not been conducted. Selective serotonin re-uptake inhibitors (SSRIs) may have a role to play in TCA-resistant patients as a result of their superior tolerability; monoamine oxidase inhibitors (MAOIs) also have a significant therapeutic role. ECT has an important role to play in patients who failed to respond to successive drug therapies. Of the various add-on therapies, thyroid augmentation (triiodothyronine) of antidepressant treatment has shown promise, and definite benefits have been established for lithium augmentation. Evidence has emerged to show that lithium is not only effective as an adjunct to TCA therapy, but also to the better tolerated SSRIs. However, further trials will be necessary to determine the optimal dosage and treatment duration for lithium augmentation. PMID- 22297240 TI - Reduction in inappropriate prevention of urinary tract infections in long-term care facilities. AB - BACKGROUND: Urinary tract infection (UTI) is the most common diagnosis made in prescribing antimicrobials in long-term care facilities (LTCF). The diagnostic criteria for UTI vary among institutions and prescribers. Our aim was to reduce the inappropriate use of antimicrobials in LTCFs. METHODS: A team comprising infectious disease consultant, infection control nurse, and geriatrician visited all LTCFs for older persons (2,321 patients in 25 primary care hospitals and 39 nursing homes and dementia units) in the Central Finland Healthcare District (population 267,000) during 2004-2005. The site visits consisted of a structured interview concerning patients, ongoing systematic antimicrobials, and diagnostic practices for UTI. Following the visits, regional guidelines for prudent use of antimicrobials in LTCFs were published, and the use of antimicrobials was followed up by an annual questionnaire. RESULTS: The proportions of patients receiving antimicrobials in 2005, 2006, 2007, and 2008 were 19.9%, 16.9%, 16.2%, and 15.4%, respectively. Most of the antibiotics were used for UTI (range by year, 66.6%-81.1%). From 2005 through 2008, the proportion of patients on antibiotic prophylaxis for UTI decreased from 13% to 6%. The decrease was statistically significant in both types of settings. CONCLUSION: The visits and guidelines were associated with a reduction in the usage of antimicrobials. To sustain this, UTI surveillance and close collaboration between infection control experts and LTCFs are crucial. PMID- 22297241 TI - Indwelling urinary catheter management and catheter-associated urinary tract infection prevention practices in Nurses Improving Care for Healthsystem Elders hospitals. AB - BACKGROUND: Indwelling urinary catheters (IUCs) are commonly used in hospitalized patients, especially elders. Catheter-associated urinary tract infections (CAUTIs) account for 34% of all health care associated infections in the United States, associated with excess morbidity and health care costs. Adherence to CAUTI prevention practices has not been well described. METHODS: This study used an electronic survey to examine IUC care practices for CAUTI prevention in 3 areas-(1) equipment and alternatives and insertion and maintenance techniques; (2) personnel, policies, training, and education; and (3) documentation, surveillance, and removal reminders-at 75 acute care hospitals in the Nurses Improving the Care of Healthsystem Elders (NICHE) system. RESULTS: CAUTI prevention practices commonly followed included wearing gloves (97%), handwashing (89%), maintaining a sterile barrier (81%), and using a no-touch insertion technique (73%). Silver-coated catheters were used to varying degrees in 59% of the hospitals; 4% reported never using a catheter-securing device. Urethral meatal care was provided daily by 43% of hospitals and more frequently that that by 41% of hospitals. Nurses were the most frequently reported IUC inserters. Training in aseptic technique and CAUTI prevention at the time of initial nursing hire was provided by 64% of hospitals; however, only 47% annually validated competency in IUC insertion. Systems for IUC removal were implemented in 56% of hospitals. IUC documentation and routine CAUTI surveillance practices varied widely. CONCLUSIONS: Although many CAUTI prevention practices at NICHE hospitals are in alignment with evidence-based guidelines, there is room for improvement. Further research is needed to identify the effect of enhanced compliance with CAUTI prevention practices on the prevalence of CAUTI in NICHE hospitals. PMID- 22297242 TI - Multichannel transceiver dual-tuned RF coil for proton/sodium MR imaging of knee cartilage at 3 T. AB - Sodium magnetic resonance (MR) imaging is a promising technique for detecting changes of proteoglycan (PG) content in cartilage associated with knee osteoarthritis. Despite its potential clinical benefit, sodium MR imaging in vivo is challenging because of intrinsically low sodium concentration and low MR signal sensitivity. Some of the challenges in sodium MR imaging may be eliminated by the use of a high-sensitivity radiofrequency (RF) coil, specifically, a dual tuned (DT) proton/sodium RF coil which facilitates the co-registration of sodium and proton MR images and the evaluation of both physiochemical and structural properties of knee cartilage. Nevertheless, implementation of a DT proton/sodium RF coil is technically difficult because of the coupling effect between the coil elements (particularly at high field) and the required compact design with improved coil sensitivity. In this study, we applied a multitransceiver RF coil design to develop a DT proton/sodium coil for knee cartilage imaging at 3 T. With the new design, the size of the coil was minimized, and a high signal-to-noise ratio (SNR) was achieved. DT coil exhibited high levels of reflection S11 (~-21 dB) and transmission coefficient S12 (~-19 dB) for both the proton and sodium coils. High SNR (range 27-38) and contrast-to-noise ratio (CNR) (range 15-21) were achieved in sodium MR imaging of knee cartilage in vivo at 3-mm(3) isotropic resolution. This DT coil performance was comparable to that measured using a sodium-only birdcage coil (SNR of 28 and CNR of 20). Clinical evaluation of the DT coil on four normal subjects demonstrated a consistent acquisition of high resolution proton images and measurement of relative sodium concentrations of knee cartilages without repositioning of the subjects during the same MR scanning session. PMID- 22297243 TI - Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international, randomised, parallel, placebo-controlled clinical trial. AB - BACKGROUND: Tadalafil improved lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH; LUTS/BPH) in clinical studies but has not been evaluated together with an active control in an international clinical study. OBJECTIVE: Assess tadalafil or tamsulosin versus placebo for LUTS/BPH. DESIGN, SETTING, AND PARTICIPANTS: A randomised, double-blind, international, placebo controlled, parallel-group study assessed men >=45 yr of age with LUTS/BPH, International Prostate Symptom Score (IPSS) >=13, and maximum urinary flow rate (Q(max)) >=4 to <=15ml/s. Following screening and washout, if needed, subjects completed a 4-wk placebo run-in before randomisation to placebo (n=172), tadalafil 5mg (n=171), or tamsulosin 0.4mg (n=168) once daily for 12 wk. MEASUREMENTS: Outcomes were assessed using analysis of covariance (ANCOVA) or ranked analysis of variance (ANOVA) (continuous variables) and Cochran-Mantel Haenszel test or Fisher exact test (categorical variables). RESULTS AND LIMITATIONS: IPSS significantly improved versus placebo through 12 wk with tadalafil (-2.1; p=0.001; primary efficacy outcome) and tamsulosin (-1.5; p=0.023) and as early as 1 wk (tadalafil and tamsulosin both -1.5; p<0.01). BPH Impact Index significantly improved versus placebo at first assessment (week 4) with tadalafil (-0.8; p<0.001) and tamsulosin (-0.9; p<0.001) and through 12 wk (tadalafil -0.8, p=0.003; tamsulosin -0.6, p=0.026). The IPSS Quality-of-Life Index and the Treatment Satisfaction Scale-BPH improved significantly versus placebo with tadalafil (both p<0.05) but not with tamsulosin (both p>0.1). The International Index of Erectile Function-Erectile Function domain improved versus placebo with tadalafil (4.0; p<0.001) but not tamsulosin (-0.4; p=0.699). Q(max) increased significantly versus placebo with both tadalafil (2.4ml/s; p=0.009) and tamsulosin (2.2ml/s; p=0.014). Adverse event profiles were consistent with previous reports. This study was limited in not being powered to directly compare tadalafil versus tamsulosin. CONCLUSIONS: Monotherapy with tadalafil or tamsulosin resulted in significant and numerically similar improvements versus placebo in LUTS/BPH and Q(max). However, only tadalafil improved erectile dysfunction. TRIAL REGISTRATION: Clinicaltrials.gov ID NCT00970632. PMID- 22297246 TI - Managing the risks of extreme weather: IPCC Special Report. PMID- 22297244 TI - Efficacy and safety of everolimus in elderly patients with metastatic renal cell carcinoma: an exploratory analysis of the outcomes of elderly patients in the RECORD-1 Trial. AB - BACKGROUND: Elderly patients with metastatic renal cell carcinoma (mRCC) may require special treatment considerations, particularly when comorbidities are present. An understanding of the efficacy and safety of targeted agents in elderly patients with mRCC is essential to provide individualized therapy. OBJECTIVE: To evaluate the efficacy and safety of everolimus in elderly patients (those >= 65 and >= 70 yr of age) enrolled in RECORD-1. DESIGN, SETTING, AND PARTICIPANTS: The multicenter randomized RECORD-1 phase 3 trial (Clinicaltrials.gov identifier, NCT00410124; http://www.clinicaltrials.gov) enrolled patients with mRCC who progressed during or within 6 mo of stopping sunitinib and/or sorafenib treatment (n=416). INTERVENTION: Everolimus 10mg once daily (n=277) or placebo (n=139) plus best supportive care. Treatment was continued until disease progression or unacceptable toxicity. MEASUREMENTS: Median progression-free survival (PFS), median overall survival (OS), and time to deterioration in Karnofsky performance status (TTD-KPS) were assessed using the Kaplan-Meier method; the log-rank test was used to compare treatment arms. Other outcomes evaluated included reduction in tumor burden, overall response rate (ORR), and safety. RESULTS AND LIMITATIONS: In RECORD-1, 36.8% of patients were >= 65 yr and 17.5% were >= 70 yr of age. PFS, OS, TTD-KPS, reduction in tumor burden, and ORR were similar in the elderly and the overall RECORD-1 population. Everolimus was generally well tolerated in elderly patients, and most adverse events were grade 1 or 2 in severity. The toxicity profile of everolimus was generally similar in older patients and the overall population; however, peripheral edema, cough, rash, and diarrhea were reported more frequently in the elderly regardless of treatment. The retrospective nature of the analyses was the major limitation. CONCLUSIONS: Everolimus is effective and tolerable in elderly patients with mRCC. When selecting targeted therapies in these patients, the specific toxicity profile of each agent and any patient comorbidities should be considered. PMID- 22297247 TI - Applied investigation on the interaction of hazardous elements binding on ultrafine and nanoparticles in Chinese anthracite-derived fly ash. AB - A multifaceted instrumental approach was employed to determine the chemistry and mineralogy of pulverized-coal-combustion fly ashes from two Chinese power plants. Techniques included traditional optical microscopy, X-ray diffraction, and chemical analysis along with a variety of electron beam methods. The aim is to demonstrate and bring together the wide variety of procedures dealing with F as the key element of concern, and determining its location in the mineral nanoparticles. The Hg content of the Anwen (Songzao coalfield) fly ashes is higher than that of the Diandong (East Yunnan) fly ashes, possibly owing to the greater C and Cl in the Anwen fly ashes. Both fly ash sources contain a variety of amorphous and nano-crystalline trace-element-bearing particles, both associated with multi-walled carbon nanotubes and as particles independent of carbons. PMID- 22297248 TI - The effects of operating conditions on particulate matter exhaust from diesel locomotive engines. AB - Numerous reports have shown that fine particulates threaten human health. Since their health impact is associated with both mass and number concentrations, it is necessary to evaluate the emission standards for particulate mass accordingly. This study examined the particulate matter characteristics of diesel locomotive engine exhaust at various engine ratings. Diesel engine exhaust was collected via a dilution tunnel and the concentration and size distribution of fine particles were measured by a scanning mobility particle sizer. Exhaust gasses were measured simultaneously by a stack sampler. The maximum carbon monoxide emission was reached at 59% of the maximum rating, after which emissions decreased. The particle count median diameter increased with the engine rating, until a maximum was reached at 40% of the maximum rating. Most exhaust particles were nanoparticles with the nuclei mode range, a particle diameter (D(P))<50 nm. The increase in particles with the accumulation mode range, 50=180/110 mm Hg, or accompanied with diabetes or three well-established cardiovascular risk factors); the other 759 patients were at mid-to-low risks. Lower birth weight (<2,500 g: odds ratio (OR) = 1.67, P = 0.02; 2,500- <3,000 g: OR = 1.64, P < 0.01; 3,000- <3,500 g, OR = 1.40, P = 0.01), family history of hypertension (OR = 1.73, P < 0.01), poor education (OR = 1.76, P < 0.01), and alcoholism (OR = 3.05, P < 0.01) significantly predicted later-life high-risk hypertension. For participants with hypertensive family history (57.7%), the association with birth weight became nonsignificant, but poor education (OR = 2.33, P < 0.01) and alcoholism (OR = 3.10, P = 0.01) remained important. For participants without hypertensive family history (42.3%), the effects of lower birth weight (<2,500 g: OR = 2.26, P = 0.02; 2,500- <3,000 g: OR = 1.91, P = 0.01; 3,000- <3,500 g, OR = 1.78, P = 0.01) and alcoholism (OR = 3.23, P < 0.01) remained significant. CONCLUSION: Low birth weight, low education, alcoholism, and hypertensive family history are linked to later-life hypertensive status. Low birth weight is also partly associated with one's genetic background; whereas the association with education and alcoholism are independent from hypertensive family history. PMID- 22297261 TI - Influence of alkali and alkaline earth elements on the uptake of radionuclides by Pleurototus eryngii fruit bodies. AB - In the literature, there are many data available on radionuclide contents and their transfer to different species of mushrooms. There are some variables, however, which affect the transfer but are very difficult to observe in collected wild mushrooms. An example is the effect of different concentrations of alkali and alkaline earth elements in the soil. Modification of these concentrations in the soil solution has traditionally been used as a countermeasure to deal with radioactively contaminated areas. In the present work, fruiting bodies of Pleurotus eryngii, a saprophytic mushroom, were grown under controlled laboratory conditions, varying the content of alkali (potassium and caesium) and alkaline earth (calcium and strontium) elements. The transfer of (134)Cs, (85)Sr, and (60)Co (added to the cultures) and of natural (210)Pb was analysed by increasing the content of each stable element considered. A significant, but nonlinear, enhancement of stable caesium and (134)Cs was observed with increasing content of stable caesium in the substrate/mycelium. The transfer of (85)Sr decreased with the addition of each stable cation, whereas the (60)Co and (210)Pb transfers were unaffected. PMID- 22297262 TI - Predictors of low back pain in physically active conscripts with special emphasis on muscular fitness. AB - BACKGROUND CONTEXT: Association between low physical fitness and low back pain (LBP) is contradictory in previous studies. PURPOSE: The objective of the present prospective cohort study was to investigate the predictive associations of various intrinsic risk factors in young conscripts for LBP, with special attention to physical fitness. STUDY DESIGN: A prospective cohort study. PATIENT SAMPLE: A representative sample of Finnish male conscripts. In Finland, military service is compulsory for male citizens and 90% of young men enter into the service. OUTCOME MEASURES: Incidence of LBP and recurrent LBP prompting a visit at the garrison health clinic during 6-month military training. METHODS: Four successive cohorts of 18- to 28-year-old male conscripts (N=982) were followed for 6 months. Conscripts with incidence of LBP were identified and treated at the garrison clinic. Predictive associations between intrinsic risk factors and LBP were examined using multivariate Cox proportional hazard models. RESULTS: The cumulative incidence of LBP was 16%, the incidence rate being 1.2 (95% confidence interval [CI], 1.0-1.4) per 1,000 person-days. Conscripts with low educational level had increased risk for incidence of LBP (hazard ratio [HR], 1.6; 95% CI, 1.1-2.3). Conscripts with low dynamic trunk muscle endurance and low aerobic endurance simultaneously (ie, having coimpairment) at baseline also had an increased risk for incidence of LBP. The strongest risk factor was coimpairment of trunk muscular endurance in tests of back lift and push-up (HR, 2.8; 95% CI, 1.4-5.9). CONCLUSIONS: The increased risk for LBP was observed among young men who had a low educational level and poor fitness level in both muscular and aerobic performance. PMID- 22297263 TI - Aggrecan: Beyond cartilage and into the brain. AB - Aggrecan is well-studied in cartilage but its expression and function in the central nervous system has only recently begun to be appreciated. Aggrecan plays an important role in the organization of the neural extracellular space by binding and organizing hyaluronan to the cell surface through interactions with link protein and tenascins forming a large aggregated quaternary complex. While all members of the lectican family to which aggrecan belongs are thought to mediate similar roles in organizing the neural matrix, aggrecan is unique in that it is the only family member found almost exclusively in an enigmatic matrix substructure called the perineuronal net. Current work has established a critical role for perineuronal nets and aggrecan in regulating developmental neural plasticity and in the recover from injury. In this review we focus on the structure, expression and function of aggrecan in the central nervous system. PMID- 22297264 TI - Cardiac MR perfusion image processing techniques: a survey. AB - First-pass cardiac MR perfusion (CMRP) imaging has undergone rapid technical advancements in recent years. Although the efficacy of CMRP imaging in the assessment of coronary artery diseases (CAD) has been proven, its clinical use is still limited. This limitation stems, in part, from manual interaction required to quantitatively analyze the large amount of data. This process is tedious, time consuming, and prone to operator bias. Furthermore, acquisition and patient related image artifacts reduce the accuracy of quantitative perfusion assessment. With the advent of semi- and fully automatic image processing methods, not only the challenges posed by these artifacts have been overcome to a large extent, but a significant reduction has also been achieved in analysis time and operator bias. Despite an extensive literature on such image processing methods, to date, no survey has been performed to discuss this dynamic field. The purpose of this article is to provide an overview of the current state of the field with a categorical study, along with a future perspective on the clinical acceptance of image processing methods in the diagnosis of CAD. PMID- 22297265 TI - Relapsing dorsal midbrain syndrome following interventions for hydrocephalus in aqueductal stenosis. AB - Dorsal midbrain syndrome (DMS) is a recognized clinical manifestation of increased intracranial pressure (ICP) associated with ventricular enlargement, especially in shunt malfunction, but the mechanism by which DMS occurs in this setting is unsettled. We report a patient with triventriculomegaly attributed to aqueductal narrowing by a tectal mass who went through 2 cycles of developing and resolving DMS promptly after undergoing interventions that altered the size of the posterior third ventricle and proximal aqueduct but probably did not markedly alter ICP. This case provides additional evidence that DMS in this setting is caused by deformation of the dorsal midbrain region produced by rapid expansion of the posterior third ventricle or proximal aqueduct. PMID- 22297266 TI - Diagnostic uncertainty due to optic disc drusen. AB - An 80-year-old woman developed swollen optic nerves with hemorrhages associated with optic disc drusen. Hemorrhagic complications of optic disc drusen are discussed. PMID- 22297267 TI - Aerodynamically assisted bio-jetting of hematopoietic stem cells. AB - The research reported in this communication demonstrates the emerging direct cell handling technology now widely referred to as aerodynamically assisted bio jetting. This is a non-electric field driven approach which directly competes with bio-electrosprays. The technology in these investigations has been explored for the direct handling of live murine primary hematopoietic stem cells. The viability studies demonstrate the complete inertness of this technology for handling such cells for a wide range of applications in both basic biology and clinical medicine. Interestingly these studies pave the way for this technology to undergo development as a flow cell for utility as a sheathless cell most useful in flow cytometry. PMID- 22297268 TI - Ultrafast primary processes of an iron-(III) azido complex in solution induced with 266 nm light. AB - The ultrafast photo-induced primary processes of the iron-(III) azido complex, [Fe(III)N(3)(cyclam-acetato)] PF(6) (1), in acetonitrile solution at room temperature were studied using femtosecond spectroscopy with ultraviolet (UV) excitation and mid-infrared (MIR) detection. Following the absorption of a 266 nm photon, the complex undergoes an internal conversion back to the electronic doublet ground state at a time scale below 2 ps. Subsequently, the electronic ground state vibrationally cools with a characteristic time constant of 13 ps. A homolytic bond cleavage was also observed by the appearance of ground state azide radicals, which were identified by their asymmetric stretching vibration at 1659 cm(-1). The azide radical recombines in a geminate fashion with the iron containing fragment within 20 ps. The cage escape leading to well separated fragments after homolytic Fe-N bond breakage was found to occur with a quantum yield of 35%. Finally, non-geminate recombination at nanosecond time scales was seen to further reduce the photolytic quantum yield to below 20% at a wavelength of 266 nm. PMID- 22297269 TI - Patch-clamp capacitance measurements and Ca2+ imaging at single nerve terminals in retinal slices. AB - Visual stimuli are detected and conveyed over a wide dynamic range of light intensities and frequency changes by specialized neurons in the vertebrate retina. Two classes of retinal neurons, photoreceptors and bipolar cells, accomplish this by using ribbon-type active zones, which enable sustained and high-throughput neurotransmitter release over long time periods. ON-type mixed bipolar cell (Mb) terminals in the goldfish retina, which depolarize to light stimuli and receive mixed rod and cone photoreceptor input, are suitable for the study of ribbon-type synapses both due to their large size (~10-12 MUm diameter) and to their numerous lateral and reciprocal synaptic connections with amacrine cell dendrites. Direct access to Mb bipolar cell terminals in goldfish retinal slices with the patch-clamp technique allows the measurement of presynaptic Ca(2+) currents, membrane capacitance changes, and reciprocal synaptic feedback inhibition mediated by GABA(A) and GABA(C) receptors expressed on the terminals. Presynaptic membrane capacitance measurements of exocytosis allow one to study the short-term plasticity of excitatory neurotransmitter release. In addition, short-term and long-term plasticity of inhibitory neurotransmitter release from amacrine cells can also be investigated by recordings of reciprocal feedback inhibition arriving at the Mb terminal. Over short periods of time (e.g. ~10 s), GABAergic reciprocal feedback inhibition from amacrine cells undergoes paired pulse depression via GABA vesicle pool depletion. The synaptic dynamics of retinal microcircuits in the inner plexiform layer of the retina can thus be directly studied. The brain-slice technique was introduced more than 40 years ago but is still very useful for the investigation of the electrical properties of neurons, both at the single cell soma, single dendrite or axon, and microcircuit synaptic level. Tissues that are too small to be glued directly onto the slicing chamber are often first embedded in agar (or placed onto a filter paper) and then sliced. In this video, we employ the pre-embedding agar technique using goldfish retina. Some of the giant bipolar cell terminals in our slices of goldfish retina are axotomized (axon-cut) during the slicing procedure. This allows us to isolate single presynaptic nerve terminal inputs, because recording from axotomized terminals excludes the signals from the soma-dendritic compartment. Alternatively, one can also record from intact Mb bipolar cells, by recording from terminals attached to axons that have not been cut during the slicing procedure. Overall, use of this experimental protocol will aid in studies of retinal synaptic physiology, microcircuit functional analysis, and synaptic transmission at ribbon synapses. PMID- 22297270 TI - An appeal to medical journal editors: the need for a full description of laboratory methods and specimen handling in clinical study reports. PMID- 22297271 TI - Comparative study of tramadol combined with dexamethasone and diclofenac sodium in third-molar surgery. AB - The aim of this randomized, double-blind clinical trial was to investigate the effect of preemptive analgesia with a combination of tramadol+dexamethasone or tramadol+diclofenac sodium. The study included 30 patients (age range: 16-30 years), who were randomly assigned to 2 groups by the split-mouth method. Postoperative pain was assessed with a visual analogue scale at 4, 6, 12, 24, and 48 h postoperatively (p.o.h.). Swelling was measured at 48 p.o.h. Maximal interincisor distance was measured at 48 p.o.h. and 7 postoperative days (p.o.d.). Significant differences in postoperative pain intensity were detected between the drug combinations at 4, 6, and 12p.o.h., suggesting the importance of preemptive analgesia. Patients treated with tramadol+dexamethasone showed lower pain scores compared to the tramadol+diclofenac sodium combination, larger postoperative mouth opening, and less swelling. The tramadol+dexamethasone combination also was more effective than tramadol+diclofenac sodium at reducing inflammation. PMID- 22297272 TI - Current trends and future perspectives of bone substitute materials - from space holders to innovative biomaterials. AB - An autologous bone graft is still the ideal material for the repair of craniofacial defects, but its availability is limited and harvesting can be associated with complications. Bone replacement materials as an alternative have a long history of success. With increasing technological advances the spectrum of grafting materials has broadened to allografts, xenografts, and synthetic materials, providing material specific advantages. A large number of bone-graft substitutes are available including allograft bone preparations such as demineralized bone matrix and calcium-based materials. More and more replacement materials consist of one or more components: an osteoconductive matrix, which supports the ingrowth of new bone; and osteoinductive proteins, which sustain mitogenesis of undifferentiated cells; and osteogenic cells (osteoblasts or osteoblast precursors), which are capable of forming bone in the proper environment. All substitutes can either replace autologous bone or expand an existing amount of autologous bone graft. Because an understanding of the properties of each material enables individual treatment concepts this review presents an overview of the principles of bone replacement, the types of graft materials available, and considers future perspectives. Bone substitutes are undergoing a change from a simple replacement material to an individually created composite biomaterial with osteoinductive properties to enable enhanced defect bridging. PMID- 22297273 TI - Cell proliferation in the hippocampus and in the heart is modified by exposure to repeated stress and treatment with memantine. AB - The present studies were aimed to verify the hypothesis that treatment with memantine, a low affinity NMDA glutamate receptor antagonist, can reduce possible stress-induced alterations in cell proliferation in the hippocampus and in the heart and has consequences on stress hormone release. Adult male Wistar rats were exposed to repeated hypokinesis (movement restraint, 2 h daily) or remained undisturbed and they were treated with memantine (5 mg/kg/day, s.c.) or vehicle for 8 days. On the day 7, all animals were injected with 5-bromo-2'-deoxyuridine (BrdU), a marker of cell proliferation. The mild form of chronic stress used resulted only in moderate decrease in BrdU incorporation into DNA in the hippocampus, while the same stimulus caused a pronounced reduction of the new cells formed in left heart ventricle. In both tissues, stress-induced reduction in cell proliferation was more evident in memantine-treated rats. Memantine failed to modify hormones of the hypothalamic-pituitary-adrenocortical axis, while the treatment increased plasma renin activity. The present study demonstrates that treatment with memantine potentiated rather than prevented stress-induced reduction of cell proliferation. We have shown that stress exposure may induce a reduction in cell proliferation in the heart, even in a higher extent than that in the hippocampus. Effects of memantine under stress conditions might be relevant with respect to clinical use of memantine, which is being used in the treatment of neurodegenerative diseases. PMID- 22297274 TI - Determining the level of sleepiness in the American population and its correlates. AB - OBJECTIVE: To assess the prevalence, to determine the risk factors and to evaluate the impacts of excessive sleepiness in the general population. METHOD: It is a cross-sectional telephone study using a representative sample consisting of 8937 non-institutionalized individuals aged 18 or over living in Texas, New York and California. They represented a total of 62.8 million inhabitants. The participation rate was 85.6% in California, 81.3% in New York and 83.2% in Texas. Interviews were managed by the Sleep-EVAL expert system. The questionnaire included questions on sleeping habits, life habits, health, DSM-IV mental disorders, DSM-IV and ICSD sleep disorders. RESULTS: As many as 19.5% of the sample reported having moderate excessive sleepiness and 11.0% reported severe excessive sleepiness. Moderate excessive sleepiness was comparable between men and women but severe excessive sleepiness was higher in women (8.6% vs. 13.0%). Factors associated with moderate excessive sleepiness were sleeping 6 h or less per main sleep episode (OR:2.0); OSAS (OR:2.0); insomnia disorder (OR:2.4); Restless Legs Syndrome (OR: 1.8) major depressive disorder (OR: 1.7); anxiety disorder (OR:1.5) and use of tricyclic antidepressant (OR: 2.1) presence of heart disease (OR: 1.5), cancer (1.8) and chronic pain (1.3). Factors associated with severe excessive sleepiness were similar with the addition of being a woman (OR:1.5), alcohol dependence (OR: 1.4), bipolar disorder (OR: 2.1), use of over the-counter sleeping pills (OR: 2.5), narcotic analgesics (OR: 3.4), Antidepressants (other than SSRI or tricyclic) and presence of gastro-esophageal reflux disease (OR:1.6). Sleepy individuals were twice as likely than non-sleepy participants to have had accidents while they were at the wheel of a vehicle during the previous year. CONCLUSIONS: Excessive sleepiness is highly prevalent in the American population. It was strongly associated with insufficient sleep and various sleep disorders as well as mental and organic diseases. PMID- 22297275 TI - Modifying effect of prenatal care on the association between young maternal age and adverse birth outcomes. AB - OBJECTIVES: The objectives were to investigate the prevalence of adverse birth outcomes according to maternal age range in the city of Rio de Janeiro, Brazil, in 2002, and to evaluate the association between maternal age range and adverse birth outcomes using additive interaction to determine whether adequate prenatal care can attenuate the harmful effect of young age on pregnancy outcomes. METHODS: A cross-sectional analysis was performed in women up to 24 years of age who gave birth to live children in 2002 in the city of Rio de Janeiro. To evaluate adverse outcomes, the exposure variable was maternal age range, and the outcome variables were very preterm birth, low birth weight, prematurity, and low 5-minute Apgar score. The presence of interaction was investigated with the composite variable maternal age plus prenatal care. The proportions and respective 95% confidence intervals were calculated for adequate schooling, delivery in a public maternity hospital, and adequate prenatal care, and the outcomes according to maternal age range. The chi-square test was used. The association between age range and birth outcomes was evaluated with logistic models adjusted for schooling and type of hospital for each prenatal stratum and outcome. Attributable proportion was calculated in order to measure additive interaction. RESULTS: Of the 40,111 live births in the sample, 1.9% corresponded to children of mothers from 10-14 years of age, 38% from 15-19 years, and 59.9% from 20-24 years. An association between maternal age and adverse outcomes was observed only in adolescent mothers with inadequate prenatal care, and significant additive interaction was observed between prenatal care and maternal age for all the outcomes. CONCLUSION: Adolescent mothers and their newborns are exposed to greater risk of adverse outcomes when prenatal care fails to comply with current guidelines. PMID- 22297276 TI - The definition of "have sex" must be unique. Re: Mehta CM, et al: "sex isn't something you do with someone you don't care about": young women's definitions of sex. J Pediatr Adolesc Gynecol. 2011; 24:266-71. PMID- 22297277 TI - Pregnancy-induced hypertension "probably linked" to PFOA contamination. PMID- 22297278 TI - The phlebotomine sandfly fauna (Diptera: Psychodidae) of Kenya. AB - Visceral and cutaneous leishmaniases are endemic in some parts of Kenya, where they are transmitted by phlebobotomine sandflies of genus Phlebotomus. This review is a compilation of the currently known distribution of phlebotomine sandflies in the parts of Kenya that have been studied, from the time sandflies were first reported in the country. So far 48 species of sandflies have been identified falling in the genera Phlebotomus Rondani & Berte and Sergentomyia Franca & Parrot. Genus Phlebotomus in Kenya is represented in five subgenera, namely Phlebotomus, Larroussius, Synphlebotomus, Paraphlebotomus and Anaphlebotomus. Genus Sergentomyia has the largest number of sandflies, and is represented in four subgenera, namely Sergentomyia, Sintonius, Grassomyia and Parvidens. PMID- 22297279 TI - In vivo sensitivity monitoring of chloroquine for the treatment of uncomplicated vivax malaria in four bordered provinces of Thailand during 2009-2010. AB - BACKGROUND & OBJECTIVES: Chloroquine (CQ), followed by 14 - day primaquine, is the recommended regimen for the treatment of Plasmodium vivax infection in Thailand. CQ resistant P. vivax (CRPv) has not yet challenged the efficacy of the drug. The present study was conducted to assess the current response of P. vivax to CQ alone in Thailand. METHODS: A 28-day in vivo therapeutic efficacy study was conducted from June 2009 to December 2010 in 4 sentinel sites. Recurrence of parasitaemia and the clinical condition of patients were assessed on each visit during follow -up. The drug levels in recurrent patients' blood were measured using HPLC. Data were analyzed using the WHO 2008 program for the analysis of in vivo tests. RESULTS: Of the total 212 patients included in the study, 201 completed the 28-days follow- up, while 11 were excluded. In five patients (2.5%), parasitaemia reappeared within the 28-days follow - up. On the day of recurrent parasitaemia, the level of chloroquine/desethylchloroquine (CQ - DCQ) was above the minimum effective concentration (>100 ng/ml) in one patient, but lower in four patients. CONCLUSION: Reappearance of the parasite within 28 days of follow - up in one of five patients was due to parasite resistance to CQ. The 2.5% prevalence of CQ treatment failure for P. vivax malaria in the study areas signals the need to launch monitoring activities for CQ resistant P. vivax in malaria endemic areas in order to detect further development of parasite resistance and to estimate the level of burden across the country. PMID- 22297280 TI - Multiple filarial species microfilaraemia: a comparative study of areas with endemic and sporadic onchocerciasis. AB - BACKGROUND & OBJECTIVES: The study was aimed at determining the pattern of co occurrence of species of microfilaraemia between onchocerciasis endemic and sporadic populations. METHODS: From every consenting person of one year and above, 50 MUl of day and night blood samples were collected and processed respectively with Haemotoxylin and Giemsa as vital stains. Two skin snips (one each from the waist and the shoulder) were also taken from these individuals and processed. RESULTS: Results showed single species microfilaraemia (86.4 and 82.3%), double species microfilaraemia (12.2 and 16.9%) and triple species microfilaraemia (1.4 and 0.7%) for endemic and sporadic populations respectively. All the species had single species microfilaraemia mostly, but Mansonella perstans and Loa loa showed greatest tendency towards double and triple species microfilaraemia. The prevalence of Wuchereria bancrofti microfilaraemia among those positive for Onchocerca volvulus was significantly lower than the overall prevalence of Wuchereria bancrofti. Wuchereria bancrofti microfilaraemia was most common among those who had L. loa microfilaraemia. Wuchereria bancrofti microfilarial intensity was higher among those with M. perstans microfilaraemia than among those positive for any of the other filarial species. Similarly, the intensity of M. perstans microfilaraemia among those positive for W. bancrofti exceeded the overall intensity of M. perstans. CONCLUSION: It is concluded that there was no definite pattern in mf densities discernible from co- occurrence infections either in the onchocerciasis endemic or sporadic population. There could be varied outcomes of onchocerciasis infection attributable to positive or negative regulatory effects of other pathogens harbored by the victims. PMID- 22297281 TI - Abnormal findings on dipstick urinalysis of out-patients with malaria in Abakaliki, Nigeria. AB - BACKGROUND & OBJECTIVES: Malaria, one of the major health challenges of the tropics affecting about 500 million people, particularly the children and pregnant women have been associated with changes in urine compositions. The present study was undertaken to document the urinary abnormalities in malaria patients based on malaria species and the level of malaria parasitaemia. METHODS: Febrile patients (n = 365) with positive Giemsa - stained blood films for malaria recruited from Outpatient Department of Ebonyi State University Teaching Hospital, Abakaliki participated in the study. Patients were classified into two categories (+ and ++) based on parasite density. Apparently healthy individuals (n = 81), without malaria parasite on both thick and thin films of comparable age and gender acted as control group. Urine sample (10 ml) was collected from each participant and analysed using standard laboratory methods and techniques. RESULTS: Seventy - four (20.3%) of the patients had Plasmodium falciparum malaria. Although all the urine parameters were higher in the malarial patients in comparison to the control, only bilirubinuria and urobilinogenuria were statistically significant (p <0.05). Also, bilirubinuria, urobilinogenuria, haematuria and proteinuria were significantly (p < 0.05) higher in P. falciparum infection than in infections with other malaria species, but only in P. falciparum infection, bilirubinuria and urobilinogenuria were significantly (p < 0.05) higher at higher parasitaemia. CONCLUSION: Even though positive blood film for malaria parasite remains the gold standard for the diagnosis of malaria, urinary abnormalities, such as bilirubinuria, urobilinogenuria, proteinuria and haematuria may aid in identifying patients with severe malaria parasitaemia, especially the falciparum malaria. PMID- 22297282 TI - Maternal and fetal outcome of dengue fever in pregnancy. AB - BACKGROUND & OBJECTIVES: As adult dengue fever increases it also affects women with pregnancy. Dengue fever is mainly treated conservatively. However, complications like pre - eclampsia, pre- term labour, increased risk of caesarean section and fetal transmission have been noted. During dengue epidemic in our region we noted many women with dengue fever and observed certain different problems. METHODS: A retrospective analysis of all pregnant women admitted in obstetric ward with dengue fever over a period of 18 months was done. RESULTS: The striking feature observed was the presence of severe thrombocytopenia in 78.57% of the study population. In addition, coexistence of other vector borne diseases was also noted. CONCLUSION: Most cases only require conservative treatment. Only women who went into labour required platelet transfusion. Outcome seemed to correlate with gestational age of occurrence of dengue fever. PMID- 22297283 TI - Molecular screening of Plasmodium infections among migrant workers in Thailand. AB - BACKGROUND & OBJECTIVE: A cross - sectional study was conducted to determine the prevalence of Plasmodium infections among migrant workers in Thailand. METHODS: A total of 241 migrants at Kanchanaburi, Pathumthani and Nakornpathom provinces of Thailand were recruited in our surveillance. Blood samples were examined for human malaria parasites by using microscopy and semi - nested multiplex PCR (SnM- PCR). RESULTS: Laboratory diagnosis revealed 6.2% total positive rate. As compared to microscopy (26.7%), SnM- PCR was more sensitive (93.3%) for malaria. Plasmodium falciparum was predominant than P. vivax (53% : 40%, respectively). The majority of positive cases were from Myanmar workers who had low parasitaemia and without symptoms. The highest prevalence (13.7%) was found among migrant workers from Kanchanaburi province in western Thailand. CONCLUSION: These findings indicate risk of malaria transmission from migrant workers. Malaria surveillance should be included in the health- screening program for migrants in Thailand to manage this health risk. PMID- 22297284 TI - A study on pulmonary manifestations in patients with malaria from northwestern India (Bikaner). AB - BACKGROUND & OBJECTIVES: Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) are responsible for most of the global burden of malaria. With changing spectrum of clinical presentation in malaria, pulmonary system involvement has always been under diagnosed. The present study was planned to estimate the pulmonary system involvement in patients with malaria from north- western India (Bikaner). STUDY DESIGN & DESCRIPTION OF THE PATIENTS: Our study was conducted during 2007 to 2009 in 200 cases of severe malaria [Pf , Pv, and mixed (Pf + Pv)] with pulmonary involvement. It included adult patients of both sexes (145 males and 55 females) belonging to all age groups. The diagnosis of Pf and Pv was confirmed by demonstrating asexual form of parasites in peripheral blood smear and OptiMal test. MAIN OUTCOME MEASURES: Pulmonary involvement was observed in 30% (60/200) patients among which cough in 24% , dyspnea in 12%, acute respiratory distress syndrome (ARDS) in 7% , bronchitis in 3% and pneumonia in 1.5% were the major clinical manifestations of malaria. Metabolic acidosis and low oxygen saturation was observed in 7% patients. Chest X- ray abnormality in 11.5% patients, 7% had bilateral infiltrates, 1.5% had inflammatory patch and 3% had findings suggestive of bronchitis. Spirometry findings showed 17% patients had early small airway obstruction. All the patients with ARDS had poor disease outcome. RESULTS & CONCLUSION: Our results suggest that pulmonary system involvement was observed in patients infected with Pf and Pv. If these clinical presentations are ignored, it may lead to delay in diagnosis and can alter the outcome and prognosis of the disease. Therefore, early diagnosis of malaria induced ARDS can significantly affect the outcome. PMID- 22297285 TI - Preliminary characterization of N-trimethylchitosan as a nanocarrier for malaria vaccine. AB - BACKGROUND & OBJECTIVES: With the current snags from the use of Artemisinin - combination therapies (ACTs) in malaria treatment in addition to fear of cross- resistance to unrelated drugs, raising the immunocompetence of individuals in malaria endemic areas by vaccination is the best approach to malaria - free world. METHODS: Water - soluble cationic derivative, N, N, N- trimethylchitosan (TMC) was synthesized from chitosan. Nanoparticles of the TMC were prepared in various media [milliQ water, Na2CO3 (pH 10.92), Na2HPO4 (PBS, pH 9.01 and alhydrogel(r) ] which were characterized as adjuvants for possible vaccine delivery. The nanoparticles were characterized for particle size, surface charge and morphology using microscopy (Phase contrast microscope and Confocal laser scanning microscope), and Malvern zetasizer Nano - ZS. Time - resolved particle size analysis was performed after one month storage of the TMC nanoparticles at 4 degrees C. RESULTS: The result of the study showed that PBS was the best medium that produced cationic, monodispersed and stable TMC nanoparticles of < nm forming a compatibly homogeneous system even upon storage. Details of the polyelectrolyte - doped nanoparticles in PBS showed clear coatings due to Sodium poly (styrene sulfonate) [PSS, MW ~70 kDa] at the periphery of the particles and a fluorescent core with some tiny central hollow cavities implying that the nanoparticles can either entrap the vaccine candidate into the hollow cavities or adsorb them unto the surface of the peripheral polyelectrolyte coatings. INTERPRETATION & CONCLUSION: This preliminary study established that TMC has the desired qualities for the intending antigen delivery. Further research regarding the biological activity of this TMC is indicated. PMID- 22297286 TI - Comparative studies of the feeding capacity and preference of Aphyosemion gularis (Boulenger 1901) on some aquatic macroinvertebrates. AB - BACKGROUND & OBJECTIVES: An efficient larvivorous fish must show a predilection for mosquito larvae in the presence of alternative preys. This study compares the feeding capacity and preference of Aphyosemion gularis exposed to different kinds of aquatic macroinvertebrates. METHODS: Various prey organisms such as Anopheles larvae and pupae, Culex larvae, chironomid larvae and ostracods were either singly and/or jointly presented at different densities to the fish and the number of prey consumed in 12 h light and dark periods were recorded. RESULTS: The result showed that in terms of capacity and preference, the fish significantly consumed (p <0.05) more Anopheles larvae than pupae and more Anopheles larvae compared to Culex and chironomid larvae. It was also found that the fish preferred Culex larvae to chironomids larvae while significantly (p < 0.05) more Anopheles larvae were consumed compared to the more abundant ostracods. CONCLUSION: The results indicate that A. gularis is adapted to feed more on Anopheles than Culex larvae on one hand and generally preferred mosquito larvae to non - mosquito macroinvertebrates. The implication of this observation is that the presence of other non - mosquito organisms considered in this study is unlikely to divert the attention of the fish from mosquito larvae, especially Anopheles larvae. The fact that the fish are able to feed on some of the non - mosquito organisms such as chironomids and ostracods, means that they can subsist on these organisms in the absence of mosquito larvae. PMID- 22297287 TI - Geographical distribution and evaluation of mosquito larvivorous potential of Aphanius dispar (Ruppell), a native fish of Gujarat, India. AB - BACKGROUND & OBJECTIVES: Certain indigenous fish can play potential role in vector control. The study recorded distribution of Aphanius dispar (Ruppell) in its native habitats in Gujarat, India and evaluated its larval propensity for Indian mosquito vectors. METHODS: Fishes were surveyed in various districts of Gujarat and samples were collected from coastal habitats and were identified to species. Physicochemical properties of water samples were analysed in the laboratory. Five laboratory acclimatized adult fish (2.2-3 cm) released in chlorine - free water in glass jars were provided with 500 larvae daily. Five replicates were run. Daily consumption of I to IV instars of Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus was recorded separately for three days. Anopheles stephensi larval control using the fish in industrial tanks (9-180 m2 ) was evaluated. RESULTS & CONCLUSION: The fish was found in large numbers in estuarine waters, rivulets, backwaters and small dams in the districts of Kutch, Jamnagar, Patan and Anand in Gujarat. Mean daily consumption of larvae in laboratory was as follows: An. stephensi 128 +/- 0.2 to 204 +/- 6; Cx. quinquefasciatus 24 +/- 4 to 58 +/- 10; Ae. aegypti 43 +/- 5 to 68 +/- 2. In water tanks, A. dispar reduced 93% larval counts by Day 7 and 98% by Day 21 (p <0.01), showing high larval propensity. A consolidated information on bionomics, tolerance and physicochemical properties of water taken from natural habitats of A. dispar indicate its high larvivorous potential. Large - scale evaluation is warranted to evaluate its potential in vector - borne disease control. PMID- 22297288 TI - Larvicidal activity of marine algae, Sargassum swartzii and Chondria dasyphylla, against malaria vector Anopheles stephensi. AB - OBJECTIVES: The objective of this study was to evaluate larvicidal activity of native marine algae against main malaria vector Anopheles stephensi. STUDY DESIGN: The total 70% methanol (MeOH) extract and partition fractions of chloroform (CHCl3), ethylacetate (EtOAc), and MeOH from two algae, Sargassum swartzii and Chondria dasyphylla were investigated for larvicidal activities against late III and early IV instar larvae of malaria vector An. stephensi. RESULTS: Among all the fractions tested against larvae, EtOAc fraction of S. swartzii and C. dasyphylla, showed mortality rate of 96 and 95%, respectively. Probit analysis of logarithmic concentration from regression line exhibited the LC50 and LC90 values of 11.75 and 53.47 ppm respectively for S. swartzii and 10.62 and 56.39 ppm respectively for C. dasyphylla. CONCLUSION: This is the first report of larvicidal activities of two native algae against An. stephensi. We propose that the larvicidal activity of EtOAc fraction is related to the presence of semi- polar compounds. Further isolation and purification could lead to identify more potent compounds. PMID- 22297289 TI - Plasmodium vivax malaria presenting with skin rash--a case report. PMID- 22297290 TI - Spontaneous acute subdural hematoma in malaria: a case report. PMID- 22297291 TI - West Nile encephalitis presenting with severe persistent chills mimicking malaria. PMID- 22297292 TI - Development of an adjoint sensitivity field-based treatment-planning technique for the use of newly designed directional LDR sources in brachytherapy. AB - The development and application of an automated 3D greedy heuristic (GH) optimization algorithm utilizing the adjoint sensitivity fields for treatment planning to assess the advantage of directional interstitial prostate brachytherapy is presented. Directional and isotropic dose kernels generated using Monte Carlo simulations based on Best Industries model 2301 I-125 source are utilized for treatment planning. The newly developed GH algorithm is employed for optimization of the treatment plans for seven interstitial prostate brachytherapy cases using mixed sources (directional brachytherapy) and using only isotropic sources (conventional brachytherapy). All treatment plans resulted in V100 > 98% and D90 > 45 Gy for the target prostate region. For the urethra region, the D10(Ur), D90(Ur) and V150(Ur) and for the rectum region the V100cc, D2cc, D90(Re) and V90(Re) all are reduced significantly when mixed sources brachytherapy is used employing directional sources. The simulations demonstrated that the use of directional sources in the low dose-rate (LDR) brachytherapy of the prostate clearly benefits in sparing the urethra and the rectum sensitive structures from overdose. The time taken for a conventional treatment plan is less than three seconds, while the time taken for a mixed source treatment plan is less than nine seconds, as tested on an Intel Core2 Duo 2.2 GHz processor with 1GB RAM. The new 3D GH algorithm is successful in generating a feasible LDR brachytherapy treatment planning solution with an extra degree of freedom, i.e. directionality in very little time. PMID- 22297293 TI - JNK modulates FOXO3a for the expression of the mitochondrial death and mitophagy marker BNIP3 in pathological hypertrophy and in heart failure. AB - Bcl-2 E1B 19-KDa interacting protein 3 (BNIP3) is a mitochondrial death and mitophagy marker, which is involved in inducing cardiac remodeling post myocardial infarction. In this study, we show that BNIP3 expression increases in stressed cardiomyocytes in vitro and in response to pressure overload in vivo, and that its transcription is directly related to JNK activity. BNIP3 expression gradually increased in the first weeks after pressure overload and peaked at the heart failure stage. Ultrastructurally, the mitochondrial area was inversely proportional to BNIP3 expression. Both JNK and AKT activities increased with pressure overload; however, JNK signaling dominated over AKT signaling for the activation of the transcription factor FOXO3a and for the transcription of its effector, BNIP3. 3-methyladenine attenuated JNK signaling and significantly decreased BNIP3 expression and reversed cardiac remodeling in heart failure. Ultrastructurally, the mitochondrial area was significantly increased in the 3 methyladenine group compared with placebo. Moreover, adenoviral gene delivery of dominant negative JNK in a rat model of pressure overload hypertrophy abolished the increase in BNIP3 expression in response to pressure overload. These results suggest that JNK signaling is a critical modulator of the transcription factor FOXO3a driving the expression of its effector, BNIP3, in heart failure and that JNK, through BNIP3, induces mitochondrial apoptosis and mitophagy. PMID- 22297294 TI - The EIF4EBP3 translational repressor is a marker of CDC73 tumor suppressor haploinsufficiency in a parathyroid cancer syndrome. AB - Germline mutation of the tumor suppressor gene CDC73 confers susceptibility to the hyperparathyroidism-jaw tumor syndrome associated with a high risk of parathyroid malignancy. Inactivating CDC73 mutations have also been implicated in sporadic parathyroid cancer, but are rare in sporadic benign parathyroid tumors. The molecular pathways that distinguish malignant from benign parathyroid transformation remain elusive. We previously showed that a hypomorphic allele of hyrax (hyx), the Drosophila homolog of CDC73, rescues the loss-of-ventral-eye phenotype of lobe, encoding the fly homolog of Akt1s1/ PRAS40. We report now an interaction between hyx and Tor, a central regulator of cell growth and autophagy, and show that eukaryotic translation initiation factor 4E-binding protein (EIF4EBP), a translational repressor and effector of mammalian target of rapamycin (mTOR), is a conserved target of hyx/CDC73. Flies heterozygous for Tor and hyx, but not Mnn1, the homolog of the multiple endocrine neoplasia type 1 (MEN1) tumor suppressor associated with benign parathyroid tumors, are starvation resistant with reduced basal levels of Thor/4E-BP. Human peripheral blood cell levels of EIF4EBP3 were reduced in patients with CDC73, but not MEN1, heterozygosity. Chromatin immunoprecipitation demonstrated occupancy of EIF4EBP3 by endogenous parafibromin. These results show that EIF4EBP3 is a peripheral marker of CDC73 function distinct from MEN1-regulated pathways, and suggest a model whereby starvation resistance and/or translational de-repression contributes to parathyroid malignant transformation. PMID- 22297296 TI - CLIPR-59 regulates TNF-alpha-induced apoptosis by controlling ubiquitination of RIP1. AB - Tumor necrosis factor-alpha (TNF-alpha) has important roles in several immunological events by regulating apoptosis and transcriptional activation of cytokine genes. Intracellular signaling mediated by TNF-receptor-type 1 (TNFR1) is constituted by two sequential protein complexes: Complex-I containing the receptor and Complex-II-containing Caspase-8. Protein modifications, particularly ubiquitination, are associated with the regulation of the formation of these complexes. However, the underlying mechanisms remain poorly defined. Here, we identified CLIP-170-related 59 kDa protein (CLIPR-59) as a novel adaptor protein for TNFR1. Experimental reduction of CLIPR-59 levels prevented induction of apoptosis and activation of caspases in the context of TNF-alpha signaling. CLIPR 59 binds TNFR1 but dissociates in response to TNF-alpha stimulation. However, CLIPR-59 is also involved in and needed for the formation of Complex-II. Moreover, CLIPR-59 regulates TNF-alpha-induced ubiquitination of receptor interacting protein 1 (RIP1) by its association with CYLD, a de-ubiquitinating enzyme. These findings suggest that CLIPR-59 modulates ubiquitination of RIP1, resulting in the formation of Complex-II and thus promoting Caspase-8 activation to induce apoptosis by TNF-alpha. PMID- 22297297 TI - OMICS, a multidisciplinary friendship. PMID- 22297298 TI - Oligodendrocyte differentiation from adult multipotent stem cells is modulated by glutamate. AB - We used multipotent stem cells (MSCs) derived from the young rat subventricular zone (SVZ) to study the effects of glutamate in oligodendrocyte maturation. Glutamate stimulated oligodendrocyte differentiation from SVZ-derived MSCs through the activation of specific N-methyl-D-aspartate (NMDA) receptor subunits. The effect of glutamate and NMDA on oligodendrocyte differentiation was evident in both the number of newly generated oligodendrocytes and their morphology. In addition, the levels of NMDAR1 and NMDAR2A protein increased during differentiation, whereas NMDAR2B and NMDAR3 protein levels decreased, suggesting differential expression of NMDA receptor subunits during maturation. Microfluorimetry showed that the activation of NMDA receptors during oligodendrocyte differentiation elevated cytosolic calcium levels and promoted myelination in cocultures with neurons. Moreover, we observed that stimulation of MSCs by NMDA receptors induced the generation of reactive oxygen species (ROS), which were negatively modulated by the NADPH inhibitor apocynin, and that the levels of ROS correlated with the degree of differentiation. Taken together, these findings suggest that ROS generated by NADPH oxidase by the activation of NMDA receptors promotes the maturation of oligodendrocytes and favors myelination. PMID- 22297295 TI - Analysis of apoptosis methods recently used in Cancer Research and Cell Death & Disease publications. PMID- 22297299 TI - mRNA for N-Bak, a neuron-specific BH3-only splice isoform of Bak, escapes nonsense-mediated decay and is translationally repressed in the neurons. AB - mRNA for neuronal Bak (N-Bak), a splice variant of pro-apoptotic Bcl-2 family member Bak is expressed in the neurons. Surprisingly the endogeneous N-Bak protein cannot be demonstrated in the neurons, although the antibodies recognize N-Bak protein from in vitro translation or transiently transfected cells. As N Bak mRNA contains premature termination codon (PTC) at 89 nucleotides upstream from the last exon-exon junction, it could be degraded by nonsense-mediated decay (NMD) during the pioneer round of translation thus explaining the absence of the protein. We show here that the endogeneous neuronal N-Bak mRNA is not the NMD substrate, as it is not accumulating by cycloheximide treatment, it has a long lifetime, and even prevention of PTC by interfering with the alternative splicing did not lead to translation of the Bak mRNA. N-Bak protein is also not revealed by proteasome inhibitors. Our data suggest strong translational arrest of N-Bak mRNA in the neurons. We show that this arrest is partially mediated by 5' untranslated region of Bak mRNA and it is not released during mitochondrial apoptosis. PMID- 22297300 TI - Adiponectin promoter activator NP-1 reduces body weight and hepatic steatosis in high-fat diet-fed animals. AB - Enhancement of adiponectin level has been shown to have beneficial effects, including antiobesity, antidiabetic, and hepatoprotective effects. This evidence supports the therapeutic utility of adiponectin in complicated obesity. The present study characterized the in vivo effects of sustained adiponectin release by NP-1, a new class of thiazol derivative that increases adiponectin levels. Acute administration of NP-1 reduced feeding, increased plasma adiponectin, and improved insulin sensitivity without inducing malaise, as revealed by conditioned taste aversion studies. Short-term (7 days) treatment with NP-1 also reduced feeding and body weight gain and increased phosphorylation of AMPK in muscle, a main intracellular effector of adiponectin. NP-1 was also evaluated in diet induced obesity, and adult male Wistar rats were fed two different types of diet: a standard high-carbohydrate/low-fat diet (SD) and a high-fat diet (HFD). Once obesity was established, animals were treated daily with NP-1 (5 mg/kg) for 14 consecutive days. Chronic NP-1 induced body weight loss and reduction of food intake and resulted in both a marked decrease in liver steatosis and an improvement of biochemical indexes of liver damage in HFD-fed rats. However, a marked induction of tolerance in adiponectin gene transcription and release was observed after chronic NP-1 with respect to the acute actions of this drug. The present results support the role of adiponectin signaling in diet-induced obesity and set in place a potential use of compounds able to induce adiponectin release for the treatment of obesity and nonalcoholic fatty liver, with the limits imposed by the induction of pharmacological tolerance. PMID- 22297301 TI - Differential regulation of stimulated glucose transport by free fatty acids and PPARalpha or -delta agonists in cardiac myocytes. AB - Stimulation of glucose transport in response to insulin or metabolic stress is an important determinant of cardiac myocyte function and survival, particularly during ischemia-reperfusion episodes. The impact of dyslipidemia and its consequence PPAR activation on stimulated glucose transport in cardiac myocytes remains unknown. Isolated adult rat cardiac myocytes were chronically exposed to free fatty acids (FFA) or PPAR agonists. Insulin- (ISGT) and oligomycin stimulated glucose transport (OSGT) and related cell signaling were analyzed. Exposure of cardiac myocytes to FFA reduced both ISGT and OSGT. Exposure to either PPARalpha or PPARdelta agonists, but not to a PPARgamma agonist, reduced ISGT but not OSGT and increased fatty acid oxidation (FAO). The reduction in ISGT was associated with impaired insulin signaling and, in the case of PPAR stimulation, overexpression of SOCS-3, a protein known to hinder proximal insulin signaling. In contrast, the reduction of OSGT could not be explained by a reduced activity of the cellular energy-sensing system, as assessed from the maintained phosphorylation state of AMPK. Inhibition of FAO at the level of mitochondrial acylcarnitine uptake restored OSGT but not ISGT. Seemingly paradoxically, further stimulation of FAO with PPARalpha or PPARdelta agonists also restored OSGT but not ISGT. Together, these results suggest that inhibition of OSGT occurs downstream of energy gauging and is caused by some intermediate(s) of fatty acid oxidation, which does not appear to be acylcarnitines. The results indicate that the mechanisms underlying FFA-mediated inhibition of ISGT and OSGT differ remarkably. PMID- 22297302 TI - Glycomacropeptide, a low-phenylalanine protein isolated from cheese whey, supports growth and attenuates metabolic stress in the murine model of phenylketonuria. AB - Phenylketonuria (PKU) is caused by a mutation in the phenylalanine (phe) hydroxylase gene and requires a low-phe diet plus amino acid (AA) formula to prevent cognitive impairment. Glycomacropeptide (GMP) contains minimal phe and provides a palatable alternative to AA formula. Our objective was to compare growth, body composition, and energy balance in Pah(enu2) (PKU) and wild-type mice fed low-phe GMP, low-phe AA, or high-phe casein diets from 3-23 wk of age. The 2 * 2 * 3 design included main effects of genotype, sex, and diet. Fat and lean mass were assessed by dual-energy X-ray absorptiometry, and acute energy balance was assessed by indirect calorimetry. PKU mice showed growth and lean mass similar to wild-type littermates fed the GMP or AA diets; however, they exhibited a 3-15% increase in energy expenditure, as reflected in oxygen consumption, and a 3-30% increase in food intake. The GMP diet significantly reduced energy expenditure, food intake, and plasma phe concentration in PKU mice compared with the casein diet. The high-phe casein diet or the low-phe AA diet induced metabolic stress in PKU mice, as reflected in increased energy expenditure and intake of food and water, increased renal and spleen mass, and elevated plasma cytokine concentrations consistent with systemic inflammation. The low-phe GMP diet significantly attenuated these adverse effects. Moreover, total fat mass, %body fat, and the respiratory exchange ratio (CO(2) produced/O(2) consumed) were significantly lower in PKU mice fed GMP compared with AA diets. In summary, GMP provides a physiological source of low-phe dietary protein that promotes growth and attenuates the metabolic stress induced by a high-phe casein or low-phe AA diet in PKU mice. PMID- 22297303 TI - Insulin stimulates fusion, but not tethering, of GLUT4 vesicles in skeletal muscle of HA-GLUT4-GFP transgenic mice. AB - Insulin regulates glucose uptake into fat and muscle by modulating the subcellular distribution of GLUT4 between the cell surface and intracellular compartments. However, quantification of these translocation processes in muscle by classical subcellular fractionation techniques is confounded by contaminating microfibrillar protein; dynamic studies at the molecular level are almost impossible. In this study, we introduce a muscle-specific transgenic mouse model in which HA-GLUT4-GFP is expressed under the control of the MCK promoter. HA GLUT4-GFP was found to translocate to the plasma membrane and T-tubules after insulin stimulation, thus mimicking endogenous GLUT4. To investigate the dynamics of GLUT4 trafficking in skeletal muscle, we quantified vesicles containing HA GLUT4-GFP near the sarcolemma and T-tubules and analyzed insulin-stimulated exocytosis at the single vesicle level by total internal reflection fluorescence and confocal microscopy. We found that only 10% of the intracellular GLUT4 pool comprised mobile vesicles, whereas most of the GLUT4 structures remained stationary or tethered at the sarcolemma or T-tubules. In fact, most of the insulin-stimulated exocytosis emanated from pretethered vesicles, whereas the small pool of mobile GLUT4 vesicles was not significantly affected by insulin. Our data strongly suggest that the mobile pool of GLUT4 vesicles is not a major site of insulin action but rather locally distributed. Most likely, pretethered GLUT4 structures are responsible for the initial phase of insulin-stimulated exocytosis. PMID- 22297304 TI - TFE3 regulates muscle metabolic gene expression, increases glycogen stores, and enhances insulin sensitivity in mice. AB - The role of transcription factor E3 (TFE3), a bHLH transcription factor, in immunology and cancer has been well characterized. Recently, we reported that TFE3 activates hepatic IRS-2 and hexokinase, participates in insulin signaling, and ameliorates diabetes. However, the effects of TFE3 in other organs are poorly understood. Herein, we examined the effects of TFE3 on skeletal muscle, an important organ involved in glucose metabolism. We generated transgenic mice that selectively express TFE3 in skeletal muscles. These mice exhibit a slight acceleration in growth prior to adulthood as well as a progressive increase in muscle mass. In TFE3 transgenic muscle, glycogen stores were more than twofold than in wild-type mice, and this was associated with an upregulation of genes involved in glucose metabolism, specifically glucose transporter 4, hexokinase II, and glycogen synthase. Consequently, exercise endurance capacity was enhanced in this transgenic model. Furthermore, insulin sensitivity was enhanced in transgenic mice and exhibited better improvement after 4 wk of exercise training, which was associated with increased IRS-2 expression. The effects of TFE3 on glucose metabolism in skeletal muscle were different from that in the liver, although they did, in part, overlap. The potential role of TFE3 in regulating metabolic genes and glucose metabolism within skeletal muscle suggests that it may be used for treating metabolic diseases as well as increasing endurance in sport. PMID- 22297306 TI - Nondestructive volumetric 3-D chemical mapping of nickel-sulfur compounds at the nanoscale. AB - Nano-structures of nickel (Ni) and nickel subsulfide (Ni(3)S(2)) materials were studied and mapped in 3D with high-resolution x-ray nanotomography combined with full field XANES spectroscopy. This method for characterizing these phases in complex microstructures is an important new analytical imaging technique, applicable to a wide range of nanoscale and mesoscale electrochemical systems. PMID- 22297305 TI - Herbal constituent sequoyitol improves hyperglycemia and glucose intolerance by targeting hepatocytes, adipocytes, and beta-cells. AB - The prevalence of insulin resistance and type 2 diabetes increases rapidly; however, treatments are limited. Various herbal extracts have been reported to reduce blood glucose in animals with either genetic or dietary type 2 diabetes; however, plant extracts are extremely complex, and leading compounds remain largely unknown. Here we show that 5-O-methyl-myo-inositol (also called sequoyitol), a herbal constituent, exerts antidiabetic effects in mice. Sequoyitol was chronically administrated into ob/ob mice either orally or subcutaneously. Both oral and subcutaneous administrations of sequoyitol decreased blood glucose, improved glucose intolerance, and enhanced insulin signaling in ob/ob mice. Sequoyitol directly enhanced insulin signaling, including phosphorylation of insulin receptor substrate-1 and Akt, in both HepG2 cells (derived from human hepatocytes) and 3T3-L1 adipocytes. In agreement, sequoyitol increased the ability of insulin to suppress glucose production in primary hepatocytes and to stimulate glucose uptake into primary adipocytes. Furthermore, sequoyitol improved insulin signaling in INS-1 cells (a rat beta cell line) and protected INS-1 cells from streptozotocin- or H2O2-induced injury. In mice with streptozotocin-induced beta-cell deficiency, sequoyitol treatments increased plasma insulin levels and decreased hyperglycemia and glucose intolerance. These results indicate that sequoyitol, a natural, water-soluble small molecule, ameliorates hyperglycemia and glucose intolerance by increasing both insulin sensitivity and insulin secretion. Sequoyitol appears to directly target hepatocytes, adipocytes, and beta-cells. Therefore, sequoyitol may serve as a new oral diabetes medication. PMID- 22297307 TI - Tumor necrosis factor-like weak inducer of apoptosis and its potential roles in lupus nephritis. AB - INTRODUCTION: Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a recently identified proinflammatory cytokine of the TNF superfamily that functions through binding to Fn14 receptor in target cells. TWEAK has multiple biological activities. Studies show that TWEAK plays an important role in immune inflammatory diseases. Recent work has revealed that TWEAK may play an important role in the pathogenesis of kidney damage, including in systemic lupus erythematosus (SLE), where its concentration in urine was correlated with the level of activity of lupus nephritis (LN). OBJECTIVE: The major focus of this review is to discuss the recent studies on TWEAK and its possible role in the pathogenesis of LN, and the therapeutic potential of modulating this pathway in LN. RESULTS AND CONCLUSION: TWEAK plays a key role in the pathogenesis of LN through activation of multiple down-signaling pathway, inducing proinflammatory cytokines and chemokines, affecting cell proliferation/apoptosis and inducing renal IgG deposition. TWEAK blockade may be a novel therapeutic approach to reducing renal damage in SLE. PMID- 22297308 TI - Forensic psychiatry: vintage 1926 Karpman to the present. PMID- 22297309 TI - Metacognitive and social cognition deficits in patients with significant psychiatric and medical adversity: a comparison between participants with schizophrenia and a sample of participants who are HIV-positive. AB - Research exploring metacognition and social cognition in schizophrenia has tended to use control groups experiencing relatively little adversity. Therefore, it remains unclear whether the deficits found among persons with schizophrenia are merely the result of greater life adversity. To explore this issue, we assessed metacognition and social cognition among 40 participants with schizophrenia and 25 adults with HIV. We chose to explore this phenomenon in people with HIV given the literature suggesting that this group experiences significant adversity. Measures of metacognition and social cognition included the Metacognition Assessment Scale (MAS), the Hinting test, and the Bell-Lysaker Emotion Recognition Test (BLERT). After controlling for education, years since diagnosis, and memory, the schizophrenia group performed more poorly on the MAS and the Hinting test. No differences were found on the BLERT. The results are consistent with the possibility that schizophrenia is linked to decrements in metacognition and some forms of social cognition. PMID- 22297310 TI - Social cognition and global functioning in bipolar disorder. AB - The purpose of this study was to assess the role of social cognition, together with other relevant clinical variables and measures of general cognition, in the global functioning of euthymic bipolar patients. Thirty-nine euthymic outpatients fulfilling DSM-IV-TR criteria for bipolar disorder type I or II were recruited and were divided in two groups: high (n = 19) and low (n = 20) global functioning. Both groups' performance was compared in verbal and nonverbal social cognition (Faux pas test and Facial Emotion Recognition test), sustained attention and executive function. The low-functioning group showed a significant impairment in both verbal and nonverbal measurements of social cognition compared with the high-functioning group. Globally, both bipolar groups showed a significant impairment in facial emotion recognition compared with a similar sample of healthy volunteers. Social cognition may play a significant role in the clinical-functional gap of bipolar patients. PMID- 22297311 TI - Nonmedication smoking reduction program for inpatients with chronic schizophrenia: a randomized control design study. AB - People with schizophrenia are more likely to smoke, and to smoke more frequently, than those without schizophrenia. Furthermore, inpatients smoke even more frequently compared with those living in the community. In light of this, we implemented and assessed a smoking reduction intervention using a wide array of behavioral group techniques and methods in chronic hospitalized schizophrenic clients. Using a controlled design, we randomly assigned chronic schizophrenic clients to either a five-session smoking reduction intervention (n = 35) or a waiting list (WL; n = 18). We assessed self-reported smoking behavior, clinical status (Positive and Negative Syndrome Scale, Hamilton Rating Scale for Depression; Clinical Global Impression Scale for Psychosis), subjective quality of life (Quality of Life Enjoyment and Satisfaction Questionnaire-abbreviated version), and weight before and 3 months after the intervention. The intervention successfully reduced the number of cigarettes smoked compared with nonintervention. No clinical worsening or weight gain was observed. Behavioral group-oriented smoking reduction interventions can significantly reduce smoking behavior in hospitalized chronic clients with schizophrenia. PMID- 22297312 TI - Predicting social functioning in schizotypy: an investigation of the relative contributions of theory of mind and mood. AB - Theory of mind (ToM) is an aspect of social cognition that refers to the ability to make inferences about the thoughts, feelings, and intentions of other people. It is believed to be related to social functioning. Previous investigations of ToM in schizotypy have yielded mixed results. Using a correlational approach, the present study explored the relationship between schizotypal traits, ToM, neurocognition, depressed mood, and social functioning in a sample of 50 undergraduate students. Schizotypy was related to poor social functioning. Contrary to predictions, schizotypal traits were not associated with impaired ToM. In fact, schizotypal traits were associated with enhanced performance on a ToM task that involved detection of ironic statements. However, strong relationships emerged among schizotypy, depressed mood, and social functioning, highlighting the need to also examine depression when assessing the relations between elevated schizotypy and poor social functioning. PMID- 22297313 TI - Interpersonal sensitivity is correlated with sociotropy but not with autonomy in healthy subjects. AB - Interpersonal sensitivity is a depression-prone personality trait closely related to anxious attachment, whereas sociotropy and autonomy are personality vulnerability factors in the cognitive theory of depression. In the present study, the relationships of interpersonal sensitivity with sociotropy and autonomy were studied in 362 healthy subjects. Interpersonal sensitivity was assessed using the Interpersonal Sensitivity Measure (IPSM), whereas sociotropy and autonomy were evaluated using the Sociotropy and Autonomy subscales, respectively, of the Sociotropy-Autonomy Scale. The IPSM was significantly correlated with the Sociotropy subscale (beta = 0.61, p < 0.001) but not with the Autonomy subscale. All subscales of the IPSM correlated significantly with the Sociotropy subscale, and the correlation for the Separation Anxiety subscale (beta = 0.56, p < 0.001) was strongest. The present study suggests that interpersonal sensitivity is correlated with sociotropy but not with autonomy in healthy subjects. PMID- 22297314 TI - Models of intimacy of securely and avoidantly attached young adults: a narrative approach. AB - This study compared models of intimacy implicit in the narratives of young adults (mean age, 25 years) with secure (n = 13) and avoidant (n = 13) attachment styles. Participants completed an open-ended interview in which they described past and present adult love relationships. Content analysis revealed that although secure and avoidant individuals expressed needs for both closeness and distance, the meaning they attached to these needs differed. Narratives of secure individuals were more likely to include themes of caring, idealization, and passion; in contrast, the narratives of avoidant individuals were more likely to contain themes of holding, self-validation, and calmness. Avoidant individuals implicitly endorse an "infant-mother" intimacy model, whereas secure individuals seem to hold a "two-adult" intimacy model. PMID- 22297315 TI - A screening tool for social anxiety disorder in primary care: data from South Africa. AB - There is little research from low- and middle-income countries examining the psychometric properties of a screening tool for social anxiety disorder. The sensitivity and specificity of the Social Anxiety Screening Questionnaire against the Mini-International Neuropsychiatric Interview as a gold standard in social phobia diagnosis were investigated using analyses of receiver operating characteristics. The "best subsets" selection procedure was conducted to determine the best three to five questions. Three questions on the screening questionnaire that best discriminate between a positive and negative diagnosis of social anxiety disorder on the MINI module were identified. Answering yes to all three of these questions gives a false-positive rate of 0.44 and a false negative rate of 0.11. For this combination, the sensitivity was 0.84, and specificity was 0.67. Additional work is needed to develop a more accurate scale that could help increase the percentage of people who receive appropriate treatment of this debilitating disorder. PMID- 22297316 TI - Distinguishing spirituality from other constructs: not a matter of well-being but of belief in supernatural spirits. AB - We developed a new Spirituality Scale and tested the argument that the defining attribute of spirituality is belief in supernatural spirits. Study 1 (N = 1931) showed that religiosity and beliefs pertinent to supernatural spirits predicted most of the variation in spirituality. Study 2 (N = 848) showed that the stronger belief in supernatural spirits, the more the person experienced subjective spirituality; that belief in supernatural spirits had higher predictive value of spirituality than religiosity, paranormal beliefs, or values; and that most of the relationship between religiosity and spirituality could be explained through belief in supernatural spirits. Study 3 (N = 972) showed that mental or physical health, social relationships, or satisfaction in marriage or work were not associated with spirituality. In turn, finding life purposeful and inner peace in dealing with spiritual experiences correlated with spirituality. The results highlight the importance of differentiating spirituality from other psychological constructs. PMID- 22297317 TI - Should psychotherapy consider reincarnation? AB - There is increasing recognition of the need to take into account the cultural environment and belief systems of psychotherapy patients because these values reflect basic assumptions about man's nature and the cognitive references used to cope with psychological difficulties. Currently accepted psychotherapeutic approaches take no account of the belief in life after death held by most of the world's population. The World Values Survey (http://www.worldvaluessurvey.org) showed that there are large numbers of reincarnationists around the world, and whatever the reasons for believing in reincarnation, psychotherapeutic approaches should not ignore this significant group of people. Respect for patient opinions and subjective realities is a therapeutic need and an ethical duty, even though therapists may not share the same beliefs. Guidelines are suggested for professionals to develop collaborative models that help patients mobilize their intrinsic intelligence to find solutions to their complaints. PMID- 22297318 TI - A bidimensional solution for outcomes in bipolar disorder. AB - Although depressive symptoms have been consistently associated with lower quality of life and increased disability in bipolar disorder, their relation to manic symptoms is not as clear cut. A great overlap between these outcomes complicates the understanding of how they cluster together. We used exploratory factor analysis to clarify the relation between these constructs. We consecutively recruited 320 patients with bipolar disorder, and interviewers rated the Hamilton Depression and Anxiety Rating Scales, the Young Mania Rating Scale (YMRS), Clinical Global Impression (CGI), and the Global Assessment of Functioning (GAF). The self-rated Sheehan Disability Scale and the World Health Organization Quality of Life-BREF questionnaires were also collected. Two distinct and large dimensions emerged. Depression and anxiety, along with the self-rated scales, loaded in the first factor, whereas the YMRS, the GAF, and the CGI loaded in the second. These findings imply that evaluating self- and observer-rated outcomes may make up for a more thorough evaluation because each conveys unique illness information. PMID- 22297319 TI - A case of autophagia: a man who was mutilating his fingers by biting them. AB - Self-mutilating behaviors could be minor and benign, but more severe cases are usually associated with psychiatric disorders or with acquired nervous system lesions and could be life-threatening. The patient was a 66-year-old man who had been mutilating his fingers for 6 years. This behavior started as serious nail biting and continued as severe finger mutilation (by biting), resulting in loss of the terminal phalanges of all fingers in both hands. On admission, he complained only about insomnia. The electromyography showed severe peripheral nerve damage in both hands and feet caused by severe diabetic neuropathy. Cognitive decline was not established (Mini Mental State Examination score, 28), although the computed tomographic scan revealed serious brain atrophy. He was given a diagnosis of impulse control disorder not otherwise specified. His impulsive biting improved markedly when low doses of haloperidol (1.5 mg/day) were added to fluoxetine (80 mg/day). In our patient's case, self-mutilating behavior was associated with severe diabetic neuropathy, impulsivity, and social isolation. The administration of a combination of an antipsychotic and an antidepressant proved to be beneficial. PMID- 22297323 TI - Light energy harvesting with nano-dipoles. AB - We propose a new approach for converting light energy into electrical energy, based on the photogeneration of nano-dipoles at donor-acceptor interfaces. The nano-dipoles are oriented in space so as to contribute to a collective polarization that induces a potential difference across the material, sandwiched between electrodes. A current is detected in the external circuit upon illumination. Such a device would exploit many advantages of organic semiconductors and get rid of the main limitation, namely transport. We provide a proof of concept and we discuss the ideal limit of the device based on numerical simulations. This provides design guidelines to the achievement of best performances. Simulations show that the proposed device can be an appealing opportunity with giant conversion efficiency provided some technological issues are overcome. PMID- 22297324 TI - Beyond Gaussians: a study of single-spot modeling for scanning proton dose calculation. AB - Active spot scanning proton therapy is becoming increasingly adopted by proton therapy centers worldwide. Unlike passive-scattering proton therapy, active spot scanning proton therapy, especially intensity-modulated proton therapy, requires proper modeling of each scanning spot to ensure accurate computation of the total dose distribution contributed from a large number of spots. During commissioning of the spot scanning gantry at the Proton Therapy Center in Houston, it was observed that the long-range scattering protons in a medium may have been inadequately modeled for high-energy beams by a commercial treatment planning system, which could lead to incorrect prediction of field size effects on dose output. In this study, we developed a pencil beam algorithm for scanning proton dose calculation by focusing on properly modeling individual scanning spots. All modeling parameters required by the pencil beam algorithm can be generated based solely on a few sets of measured data. We demonstrated that low-dose halos in single-spot profiles in the medium could be adequately modeled with the addition of a modified Cauchy-Lorentz distribution function to a double-Gaussian function. The field size effects were accurately computed at all depths and field sizes for all energies, and good dose accuracy was also achieved for patient dose verification. The implementation of the proposed pencil beam algorithm also enabled us to study the importance of different modeling components and parameters at various beam energies. The results of this study may be helpful in improving dose calculation accuracy and simplifying beam commissioning and treatment planning processes for spot scanning proton therapy. PMID- 22297325 TI - Parallel-plate flow chamber and continuous flow circuit to evaluate endothelial progenitor cells under laminar flow shear stress. AB - The overall goal of this method is to describe a technique to subject adherent cells to laminar flow conditions and evaluate their response to well quantifiable fluid shear stresses. Our flow chamber design and flow circuit (Fig. 1) contains a transparent viewing region that enables testing of cell adhesion and imaging of cell morphology immediately before flow (Fig. 11A, B), at various time points during flow (Fig. 11C), and after flow (Fig. 11D). These experiments are illustrated with human umbilical cord blood-derived endothelial progenitor cells (EPCs) and porcine EPCs. This method is also applicable to other adherent cell types, e.g. smooth muscle cells (SMCs) or fibroblasts. The chamber and all parts of the circuit are easily sterilized with steam autoclaving. In contrast to other chambers, e.g. microfluidic chambers, large numbers of cells (> 1 million depending on cell size) can be recovered after the flow experiment under sterile conditions for cell culture or other experiments, e.g. DNA or RNA extraction, or immunohistochemistry (Fig. 11E), or scanning electron microscopy. The shear stress can be adjusted by varying the flow rate of the perfusate, the fluid viscosity, or the channel height and width. The latter can reduce fluid volume or cell needs while ensuring that one-dimensional flow is maintained. It is not necessary to measure chamber height between experiments, since the chamber height does not depend on the use of gaskets, which greatly increases the ease of multiple experiments. Furthermore, the circuit design easily enables the collection of perfusate samples for analysis and/or quantification of metabolites secreted by cells under fluid shear stress exposure, e.g. nitric oxide (Fig. 12). PMID- 22297326 TI - The calcitonin levels can sometimes mislead parathyroid surgeons in patients with chronic kidney disease and renal hyperparathyroidism: report of a case. AB - Renal hyperparathyroidism (rHPT) as a consequence of an abnormal calcium balance is a frequent complication in patients with chronic kidney disease (CKD). However, calcium homeostasis is also regulated by calcitonin. The relevance of elevated calcitonin levels in patients with rHPT is unclear. This report presents a case of a patient with CKD and mild rHPT scheduled for thyroidectomy for a suspected medullary thyroid carcinoma (MTC) within a mononodular goiter. A hemithyroidectomy with resection of both adjacent parathyroid glands and unilateral central lymph node dissection was performed. Histopathology revealed no evidence of MTC. The rHPT, calcitonin and pentagastrin test subsequently normalized and follow-up revealed no evidence for MTC within the remaining right thyroid lobe. Elevated calcitonin levels in patients with CKD may reflect a physiological response to rHPT than rather represent MTC. The thresholds for calcitonin levels need to be better defined in affected patients to determine the optimal extent of surgical resection. PMID- 22297327 TI - Light localization in nonuniformly randomized lattices. AB - We address Anderson localization of light in disordered optical lattices where the disorder strength varies across the transverse direction. Such variation changes the preferred domains where formation of localized eigenmodes is most probable, hence drastically impacting light localization properties. Thus, step like disorder results in formation of modes with different decay rates at both sides of the interface, while a smoothly varying disorder yields appearance of modes that are extended within weakly disordered domains and rapidly fade away in strongly disordered domains. PMID- 22297328 TI - Phase-matched third-harmonic generation in highly germanium-doped fiber. AB - Phase-matched third-harmonic generation is demonstrated in a germanium-doped optical fiber. Green light at 514.4 nm is generated in an LP(03) mode when a pump field at ~1543.3 nm is launched into the fiber in the fundamental LP(01) mode. The phase matching is achieved for a particular combination of the germanium doping concentration and the fiber core diameter. PMID- 22297330 TI - Photoelastic response of alkaline earth aluminosilicate glasses. AB - Understanding the structural origins of the photoelastic response in oxide glasses is important for discovering new families of zero-stress optic glasses and for developing a predictive physical model. In this Letter, we have investigated the composition dependence of the stress optic coefficient C of 32 sodium aluminosilicate glasses with different types of alkaline earth oxides (MgO, CaO, SrO, and BaO). We find that most of the composition dependence of the stress optic response can be captured by a linear regression model and that the individual contributions from the alkaline earths to C depend on the alkaline earth-oxygen bond metallicity. High bond metallicity is required to allow bonds to be distorted along both the bonding direction and perpendicular to it. These findings are valuable for understanding the photoelastic response of oxide glasses. PMID- 22297331 TI - Terahertz bandpass filters using double-stacked metamaterial layers. AB - Bandpass filters are reported based on double-stacked metamaterial layers separated by an air gap for operation at terahertz frequencies. Several stacking configurations were investigated designed for a ~0.5 THz center frequency. The filters exhibited improved spectral transmission properties when compared with conventional ones based on single metamaterial layers. 3 dB bandwidth of ~78 GHz and sidelobe suppression ratio >16 dB were determined when symmetric or asymmetric double layers were stacked. We demonstrate that superior frequency selectivity can be achieved when metamaterial layers with different unit cells are used. Good agreement was found between measured and simulated transmission response. PMID- 22297332 TI - Ultrahigh infrared normal spectral emissivity of microstructured silicon coating Au film. AB - We studied infrared normal spectral emissivity on quasi-periodic microstructured silicon, which was prepared by femtosecond laser irradiation in SF6 ambient gas, coated with 100 nm thick Au thin film. The observed emissivity is higher than any reported previously for a flat material with a thickness of less than 0.5 mm, at a temperature range of 200 degrees C to 400 degrees C. The emissivity over the measured wavelength region increases with temperature and the spike height. These results show the potential to be used as a flat blackbody source or for applications in infrared thermal sensor, detector, and stealth military technology. PMID- 22297333 TI - Widely tunable and ultrasensitive leaky-guided multimode fiber interferometer based on refractive-index-matched coupling. AB - This investigation presents a simple, widely tunable, and ultrasensitive sensor that is based on a leaky-guided multimode fiber interferometer (MMFI) operated under refractive-index-matched coupling. By use of a material with an appropriate dispersion profile around the MMFI as a cladding yields strong index-matched coupling, which performs ultrasensitive sensing in variations of the surroundings. Index matching at a single wavelength yields a coupling wavelength dip with a narrow bandwidth and a high extinction ratio of over 25 dB. The wavelength dip can also be effectively tuned, greatly shifting with a variation in temperature (T) or refractive index (RI), when the index-matched condition is satisfied. This work demonstrates that the proposed sensor responds sensitively to T with an extremely high tuning efficiency of 50 nm/ degrees C and an excellent sensitivity to RI of 113,500 nm per RI unit. PMID- 22297334 TI - Longitudinal-differential interferometry: direct imaging of axial superluminal phase propagation. AB - We introduce and demonstrate a new interferometric method called longitudinal differential (LD) interferometry, which measures the spatially resolved phase difference of the scattered field by an object relative to the illumination. This method is combined with a high-resolution interference microscope that allows recording three-dimensional field distributions in amplitude and phase. The method is applied to study the axial phase behavior of Arago spots, an effect observable in low-Fresnel-number systems behind objects with a size comparable to the wavelength. We directly observe the initial phase delay in the Arago spot and prove that the local phase velocity exceeds the speed of light in air. Such LD phase studies are applicable not only to the Arago spot but also to other kinds of light interactions with wavelength-scale objects, e.g., photonic nanojets. PMID- 22297335 TI - Design of metamaterial surfaces with broadband absorbance. AB - A simple design paradigm for making broadband ultrathin plasmonic absorbers is introduced. The absorber's unit cell is composed of subunits of various sizes, resulting in nearly 100% absorbance at multiple adjacent frequencies and high absorbance over a broad frequency range. A simple theoretical model for designing broadband absorbers is presented. It uses a single-resonance model to describe the optical response of each subunit and employs the series circuit model to predict the overall response. Validity of the circuit model relies on short propagation lengths of the surface plasmons. PMID- 22297336 TI - Pure two-dimensional polarization patterns for holographic recording. AB - Two-dimensional (2D) polarization patterns are achieved by the interference of two pairs of beams with perpendicular planes of incidence and orthogonal polarizations (i.e. linear or circular). In both cases, imposing a phase shift of pi/2 between consecutive beams contains the amplitude modulation of the optical field in the superposition region and, thus, pure 2D polarization patterns are created. The recording of these interference fields in a polarization-sensitive material, namely an amorphous azopolymer, creates reconfigurable 2D periodic microstructures with peculiar diffraction properties. PMID- 22297337 TI - Coherence-polarization mixing in resonance gratings. AB - We show, using rigorous diffraction theory, that resonance gratings can be used to transfer partial spatial correlation to partial polarization even if the incident light beam is fully polarized. The phenomenon is based on the fact that either of the two orthogonal polarization components can be coupled into the leaky waveguide mode, leading to a strong phase delay, while the other one is reflected without being coupled into the grating. Numerical demonstrations are based on a Gaussian Schell-model beam and a grating analysis performed by rigorous Fourier modal method. PMID- 22297338 TI - Solar blind photoconductivity in three-terminal devices of LaAlO3/SrTiO3 heterostructures. AB - We report observations of photoconductivity in ultrathin films of LaAlO(3) grown on (001) SrTiO(3) at several deposition temperatures. The films show pronounced metallic behavior in the dark. The conductance of this metallic state can be enhanced by ultraviolet light (350-400 nm) of a few MUW/cm(2) intensity. The decay of the photoconducting state follows stretched exponential dynamics, which can be accelerated or slowed down on the application of gate voltage, thus imparting a novel functionality to the system. PMID- 22297339 TI - Compact optical microfiber phase modulator. AB - A compact optical microfiber phase modulator with MHz bandwidth is presented. A micrometer-diameter microfiber is wound on a millimeter-diameter piezoelectric ceramic rod with two electrodes. When a voltage is applied to the piezoelectric ceramic, the rod is strained, leading to a phase change along the microfiber; because of the small size, the optical microfiber phase modulator can have as high as a few MHz bandwidth response. PMID- 22297340 TI - Reflective fiber-optic refractometer based on a thin-core fiber tailored Bragg grating reflection. AB - A novel reflective refractometer based on a thin-core fiber (TCF) sandwiched between a leading single-mode fiber (SMF) and a fiber Bragg grating (FBG) imprinted SMF stub was demonstrated. The reflection from the fiber stub occurs in two well-defined wavelength bands, corresponding to the Bragg core mode and cladding modes. The TCF section functions as a tailorable bridge between the FBG core mode reflection and the surrounding refractive index (SRI). Linear response with enhanced sensitivity of 133.26 dB/refractive index unit for temperature immune SRI measurement within the biologically desirable sensing range of 1.33 1.41 has been achieved via cost-effective power detection. PMID- 22297341 TI - Split-step finite-difference time-domain method with perfectly matched layers for efficient analysis of two-dimensional photonic crystals with anisotropic media. AB - This Letter presents a split-step (SS) finite-difference time-domain (FDTD) method for the efficient analysis of two-dimensional (2-D) photonic crystals (PhCs) with anisotropic media. The proposed SS FDTD method is formulated with perfectly matched layer boundary conditions and caters for inhomogeneous anisotropic media. Furthermore, the proposed method is derived using the efficient SS1 splitting formulas with simpler right-hand sides that are more efficient and easier to implement. A 2-D PhC cavity with anisotropic media is used as an example to validate the efficiency of the proposed method. PMID- 22297342 TI - A slow-light laser radar system with two-dimensional scanning. AB - We propose a multi-aperture slow-light laser radar with two-dimensional scanning. We demonstrate experimentally that we can use two independent slow-light mechanisms, namely dispersive delay and stimulated Brillouin scattering, to dynamically compensate the group delay mismatch among different apertures, while we use optical phase locking to control the relative phases of the optical signals emitted from different apertures, as the system steers the beam in two dimensions. PMID- 22297343 TI - Anderson localization in nonlocal nonlinear media. AB - We theoretically and numerically investigate the effect of focusing and defocusing nonlinearities on Anderson localization in highly nonlocal media. A perturbative approach is developed to solve the nonlocal nonlinear Schrodinger equation in the presence of a random potential, showing that nonlocality stabilizes Anderson states. PMID- 22297344 TI - Polarization rotator for InP rib waveguide. AB - A polarization rotator, suitable for integration in a polarization diversity optical receiver fabricated in InP technology, is proposed. The device, based on a two steps waveguide rotator, includes tapered input and output ports that provide very low insertion loss (<0.04 dB). An extinction ratio of 40 dB at 1550 nm wavelength is calculated, comparable or even superior to other state of the art polarization converters. The main advantage of the proposed design is the capability of implementation using a standard fabrication process with only two dry etch steps, significantly reducing complexity and cost. PMID- 22297345 TI - Diode-pumped green Nd:YAG laser with Q-switch and mode locking. AB - We propose a new method for achieving simultaneous operation of laser mode locking and the Q-switch technique using only a single acousto-optic modulator (AOM) with a traveling wave; this AOM was placed inside the cavity of a green emission Nd:YAG laser. The further shortening of the lasing pulse duration from 40 ps to less than 3.25 ps was obtained by the formation of a Kerr lens in a doubling-frequency crystal. At average output power of 1.5 W and pulse repetition rate of the Q-switch equal to 2 kHz, the peak power in a steady-operating laser exceeded 50 MW. PMID- 22297346 TI - Full-field technique for measuring the spectral evolution of reconfigurable photonic filters. AB - This Letter demonstrates a measurement technique based on frequency-to-time mapping and coherent detection, which enables the complete (i.e., amplitude and phase) characterization of dynamically reconfigurable photonic filters. We apply this technique to a unit cell from a silicon CMOS-compatible photonic lattice filter that has a rapidly changing transfer function with an 8.33 ns update time, 120 MHz spectral resolution, and 12 GHz bandwidth. These dynamic measurements allow characterization of transients, thermal effects, filter fidelity, and other time-dependent phenomena during switching. PMID- 22297347 TI - High power (130 mW) 40 GHz 1.55 MUm mode-locked distributed Bragg reflector lasers with integrated optical amplifiers. AB - High output power 40 GHz 1.55 MUm passively mode-locked surface-etched distributed Bragg reflector (DBR) lasers with monolithically integrated semiconductor optical amplifiers are reported. These are based on an optimized AlGaInAs/InP epitaxial structure with a three quantum well active layer and an optical trap layer. The device produces near transform limited Gaussian pulses with a pulse duration of 3.3 ps. An average output power during mode-locked operation of 130 mW was achieved with a corresponding peak power of >1 W. PMID- 22297348 TI - Time-domain multimode dispersion measurement in a higher-order-mode fiber. AB - We present a new multimode dispersion measurement technique based on the time-of flight method. The modal delay and group velocity dispersion of all excited modes in a few-mode fiber can be measured simultaneously by a tunable pulsed laser and a high speed sampling oscilloscope. A newly designed higher-order-mode fiber with large anomalous dispersion in the LP(02) mode has been characterized using this method, and experimental results are in good agreement with the designed dispersion values. The demonstrated technique is significantly simpler to implement than the existing frequency-domain or interferometry-based methods. PMID- 22297349 TI - Single-shot profilometry of rough surfaces using hyperspectral interferometry. AB - The combination of white light interferometry with hyperspectral imaging ("hyperspectral interferometry") is a recently proposed technique for single-shot measurement of 3D surface profiles. We consider for the first time its application to speckled wavefronts from optically rough surfaces. The intensity versus wavenumber signal at each pixel provides unambiguous range information despite the speckle-induced random phase shifts. Experimental results with samples undergoing controlled rigid body translation demonstrate a measurement repeatability of 460 nm for a bandwidth of approximately 30 nm. Potential applications include roughness measurement and coordinate measurement machine probes where rapid data acquisition in noncooperative environments is essential. PMID- 22297350 TI - All-fiber polarization interference filters based on 45 degrees -tilted fiber gratings. AB - We report all-fiber polarization interference filters, known as Lyot and Lyot Ohman filters, based on alternative concatenation of UV-inscribed fiber gratings with structure tilted at 45 degrees and polarization maintaining (PM) fiber cavities. Such filters generate comb-like transmission of linear polarization output. The free spectral range (FSR) of a single-stage (Lyot) filter is PM fiber cavity length dependent, as a 20 cm long cavity showed a 26.6 nm FSR while the 40 cm one exhibited a 14.8 nm FSR. Furthermore, we have theoretically and experimentally demonstrated all-fiber 2-stage and 3-stage Lyot-Ohman filters, giving more freedom in tailoring the transmission characteristics. PMID- 22297351 TI - Efficient thin-disk Tm-laser operation based on Tm:KLu(WO4)2/KLu(WO4)2 epitaxies. AB - A diode-pumped thin-disk laser based on Tm:KLu(WO4)2/KLu(WO4)2 epitaxies is realized. The emission is in the 1850-1945 nm spectral range for Tm-doping between 5 and 15 at. %. The maximum slope efficiency of 47% with respect to the absorbed power obtained with 5 at. % Tm:KLu(WO4)2/KLu(WO4)2 corresponds to a maximum output power of ~6 W in cw operation. PMID- 22297352 TI - Enhance the resolution of photonic crystal negative refraction imaging by metal grating. AB - The resolution of imaging is limited by the missing of high-frequencies information. The superlens employing negative refraction can compensate for these components. But for the directional coupling of Bloch waves and the low coupling efficiency of large-angle waves, the resolution of subwavelength imaging is not satisfactory. However, the subwavelength metallic grating can produce high-order diffracted waves carrying a lot of high-frequencies information. Therefore, this structure is used to inhibit the zero-order diffraction and enhance the high order diffraction to achieve super-resolution. PMID- 22297353 TI - Integrated multimodal endomicroscopy platform for simultaneous en face optical coherence and two-photon fluorescence imaging. AB - We report an all-fiber-optic scanning, multimodal endomicroscope capable of simultaneous optical coherence tomography (OCT) and two-photon fluorescence (TPF) imaging. Both imaging modalities share the same miniature fiber-optic scanning endomicroscope, which consists of a double-clad fiber with a core operating in single mode at both the OCT (1310 nm) and two-photon excitation (1550 nm) wavelengths, a piezoelectric two-dimensional fiber-optic beam scanner, and a miniature aspherical compound lens suitable for simultaneous acquisition of en face OCT and TPF images. A fiber-optic wavelength division multiplexer was employed in the integrated platform to combine the low coherence OCT light source and the femtosecond two-photon excitation laser into the same optical path. Preliminary imaging results of cell cultures and mouse tissue ex vivo demonstrate the feasibility of simultaneous real-time OCT and TPF imaging in a scanning endomicroscopy setting for the first time. PMID- 22297354 TI - Ultracompact polarization converter with a dual subwavelength trench built in a silicon-on-insulator waveguide. AB - The design and fabrication of an ultracompact silicon-on-insulator polarization converter is reported. The polarization conversion with an extinction ratio of 16 dB is achieved for a conversion length of only 10 MUm. Polarization rotation is achieved by inducing a vertical asymmetry by forming in the waveguide core two subwavelength trenches of different depths. By taking advantage of the calibrated reactive ion etch lag, the two depths are implemented using a single mask and etching process. The measured converter loss is -0.7 dB and the 3 dB bandwidth is 26 nm. PMID- 22297355 TI - Enhanced downconversion of UV light by resonant scattering of aluminum nanoparticles. AB - Metallic nanoparticles are known to enhance nonlinear optical processes due to a local enhancement of the optical field. This strategy has been proposed to enhance downconversion in thin film solar cells, but has various disadvantages, among which is the fact that the enhancement occurs only in a tiny volume close to the particles. We report on a very different physical mechanism that can lead to significant downconversion enhancement, namely, that of resonant light scattering, and which is a large volume effect. We show that only a tiny amount of resonantly scattering metallic (aluminum) nanoparticles is enough to create a significant enhancement of the fluorescence of dye molecules in the visible wavelength range. The strategy can be applied in general to increase the emission of UV-absorbing constituents, and is of particular use for solar energy. PMID- 22297356 TI - Wideband perfect light absorber at midwave infrared using multiplexed metal structures. AB - We experimentally demonstrate a wideband near-perfect light absorber in the midwave IR region using a multiplexed plasmonic metal structure. The wideband near-perfect light absorber is made of two different size gold metal squares multiplexed on a thin dielectric spacing layer on top of a thick metal layer in each unit cell. We also fabricate regular nonmultiplexed structure perfect light absorbers. The multiplexed structure IR absorber absorbs more than 98% of the incident light over a much wider spectral band than regular nonmultiplexed structure perfect light absorbers in the midwave IR region. PMID- 22297357 TI - Single-mode whispering gallery lasing from metal-clad GaN nanopillars. AB - An ordered hexagonal closed-packed nanopillar array is fabricated on GaN. A metal coating is then applied to encapsulate the pillars for promoting optical confinement within the cylindrical cavity. Room-temperature lasing at 373 nm is observed under pulsed excitation, at a lasing threshold of 0.42 MW/cm2. With pillar diameters of around 980 nm, the number of modes overlapping the emission spectrum is reduced, giving rise to single-mode whispering gallery stimulated emission. Finite-difference time-domain simulations are carried out for the prediction of resonant frequencies and electric field patterns corresponding to the resonant modes. PMID- 22297358 TI - 26 nJ picosecond solitons from thulium-doped single-mode master oscillator power fiber amplifier. AB - We report on an all single-mode master oscillator power fiber amplifier delivering high energy picosecond solitons at 1960 nm. The Bragg stabilized and self-starting oscillator delivers 62 pJ transform-limited pulses at 11.2 MHz pulse repetition frequency. Solitons are amplified in a core-pumped single-mode heavily thulium-doped fiber up to 26 nJ. The average and peak power are 291 mW and 7.4 kW, respectively. Pulses remain transform limited without significant self-phase-modulation distortion. We discuss the limitations of picosecond pulse amplification in a core-pumped single-mode fiber amplifier. PMID- 22297359 TI - Numerical and experimental investigation of long-period gratings in photonic crystal fiber for refractive index sensing of gas media. AB - We have used the finite-difference frequency-domain (FDFD) method to simulate the core mode to cladding mode couplings in long-period gratings (LPGs) in photonic crystal fiber (PCF). Four sets of LPG-PCF have been fabricated with respective periodicities of 590, 540, 515, and 490 MUm, resulting in corresponding resonance wavelengths (RWs) of 1241, 1399, 1494, and 1579 nm. We show both theoretically and experimentally that the longer the RW, the more sensitive the LPG-PCF is to the index change in Ar. We demonstrate a robust sensitivity of 517 nm per refractive index unit using the LPG-PCF at 1579 nm RW. PMID- 22297360 TI - Non-steady-state photoelectromotive force effect under linear and periodical phase modulation: application to detection of Doppler frequency shift. AB - Non-steady-state photoelectromotive force effect in the presence of periodical and linear phase shift was investigated both theoretically and experimentally. It was shown that superposition of oscillating and linear movements of the interference pattern leads to the appearance of the sharp peak in the frequency dependence of the photoelectromotive force output current when the frequency of periodical modulation matches the frequency of the linear phase shift. We demonstrated experimentally that this effect can be used for determination of a Doppler frequency shift between signal and reference beam. PMID- 22297361 TI - Computational polarization imaging from a single speckle image. AB - We experimentally demonstrate that imaging of the degree of polarization (DOP) can be achieved from a single intensity image acquired under coherent illumination. This computational technique is based on the analysis of the speckle characteristics in a statistically homogeneous neighborhood of the pixel. Over a variety of samples obtained experimentally, we show that a simple calibration step allows this method to quickly and simply provide correct estimated values of the DOP, with precision in agreement with theoretical predictions. It is shown that unlike linear polarimetric contrast imaging, this method remains valid on birefringent samples. PMID- 22297362 TI - Stationary one-dimensional dispersive shock waves. AB - We address shock waves generated upon the interaction of tilted plane waves with negative refractive index defects in defocusing media with linear gain and two photon absorption. We found that, in contrast to conservative media where one dimensional dispersive shock waves usually exist only as nonstationary objects expanding away from a defect or generating beam, the competition between gain and two-photon absorption in a dissipative medium results in the formation of localized stationary dispersive shock waves, whose transverse extent may considerably exceed that of the refractive index defect. One-dimensional dispersive shock waves are stable if the defect strength does not exceed a certain critical value. PMID- 22297363 TI - Three-dimensional mid-infrared photonic circuits in chalcogenide glass. AB - We report the fabrication of single-mode buried channel waveguides for the whole mid-IR transparency range of chalcogenide sulphide glasses (lambda <= 11 MUm), by means of direct laser writing. We have explored the potential of this technology by fabricating a prototype three-dimensional three-beam combiner for future application in stellar interferometry that delivers a monochromatic interference visibility of 99.89% at 10.6 MUm and an ultrahigh bandwidth (3-11 MUm) interference visibility of 21.3%. These results demonstrate that it is possible to harness the whole transparency range offered by chalcogenide glasses on a single on-chip instrument by means of direct laser writing, a finding that may be of key significance in future technologies such as astrophotonics and biochemical sensing. PMID- 22297364 TI - Graphene on SiC as a Q-switcher for a 2 MUm laser. AB - Double-layer graphene epitaxially grown on silicon carbide was used to Q-switch a Tm:YAG laser. Stable Q-switched laser pulses at the central wavelength of 2.01 MUm were obtained. The maximum average output power, pulse repetition rate, and single pulse energy were 38 mW, 27.9 kHz, and 1.74 MUJ, respectively. Our results illustrate that graphene can be used as a saturable absorber at the 2 MUm region. PMID- 22297365 TI - Magneto-optical fiber sensor based on magnetic fluid. AB - A novel magnetic field fiber sensor based on magnetic fluid is proposed. The sensor is configured as a Sagnac interferometer structure with a magnetic fluid film and a section of polarization maintaining fiber inserted into the fiber loop to produce a sinusoidal interference spectrum for measurement. The output interference spectrum is shifted as the change of the applied magnetic field strength with a sensitivity of 16.7 pm/Oe and a resolution of 0.60 Oe. The output optical power is varied with the change of the applied magnetic field strength with a sensitivity of 0.3998 dB/Oe. PMID- 22297366 TI - Double-pass self-spectral-calibration of a polarization state analyzer. AB - We present a new method that allows efficient spectral calibration for a polarization state analyzer. The procedure does not require any additional polarization optical element other than the polarization state analyzer itself. It uses a double-pass technique that can be achieved up to a very good precision. The method is illustrated using real measurements done at several wavelengths with a rotating wave plate polarization state analyzer. Alignment of axis as well as true retardation at a specific wavelength are easily obtained by a standard function fitting. PMID- 22297367 TI - Toward an electrically pumped spaser. AB - The use of surface plasmon polariton (SPP)-based waveguides can significantly reduce the size of optical interconnects, but the propagation length of SPPs is limited by Joule heating losses and does not exceed a few micrometers. In this paper, we present an SPP amplification scheme that utilizes compact electrical pumping and gives a possibility for designing really compact on-chip waveguides. Moreover, we demonstrate here numerically that this approach can be easily used to design an electrically pumped cw or pulsed spaser. PMID- 22297368 TI - Lighting spectrum to maximize colorfulness. AB - The spectrum of modern illumination can be computationally tailored considering the visual effects of lighting. We investigated the spectral profiles of the white illumination maximizing the theoretical limits of the perceivable object colors. A large number of metamers with various degrees of smoothness were generated on and around the Planckian locus, and the volume in the CIELAB space of the optimal colors for each metamer was calculated. The optimal spectrum was found at the color temperature of around 5.7*10(3) K, had three peaks at both ends of the visible band and at around 510 nm, and was 25% better than daylight and 35% better than Thornton's prime color lamp. PMID- 22297369 TI - Bio-organism detection in one-dimensional photonic crystals using electromagnetically induced transparency. AB - We propose an optical sensor that allows site-selective detection of a refractive index change occurring due to any infiltration such as a bio-organism in a porous one-dimensional photonic crystal (PC). We use the electromagnetically induced transparency (EIT) to detect and locate the infiltration. With a localized change in the refractive index, the maximum of the peak EIT transmission shifts, which is determined by tuning the control field frequency. The strong dispersion and the narrowing of the absorption free response associated with EIT within the PC form the basis of such enhanced sensitivity. PMID- 22297370 TI - Fast maximum likelihood algorithm for localization of fluorescent molecules. AB - A common task in microscopy is to fit an image of a fluorescent probe to a point spread function (PSF) in order to estimate the position of the probe. The PSF is often approximated as a Gaussian for mathematical simplicity. We show that the separable property of the Gaussian PSF enables a reduction of computational time from O(L2) to O(L), where L is the width (in pixels) of the image. When tested on realistic simulated data, our algorithm is able to localize the probes with precision close to the Cramer-Rao lower bound. PMID- 22297371 TI - Solution of large-scale plasmonic problems with the multilevel fast multipole algorithm. AB - A surface integral equation together with the multilevel fast multipole algorithm is successfully applied to fast and accurate resolution of plasmonic problems involving a large number of unknowns. The absorption, scattering, and extinction efficiencies of several plasmonic gold spheres of increasing size are efficiently obtained solving the electric and magnetic current combined-field integral equation. The numerical predictions are compared with reference analytic results to demonstrate the accuracy, suitability, and capabilities of this approach when dealing with large-scale plasmonic problems. PMID- 22297372 TI - Luminescence in epitaxial Er-doped LiNbO3 films. AB - Epitaxial Er-doped LiNbO3 films were pulsed-laser-deposited onto c-cut sapphire. Wavelength dispersion of the refractive index and the extinction coefficient was obtained by fitting the experimental transmittance spectrum to the Swanepoel formula and microscopic theory, which accounts for two resonance transitions in the electric dipole approximation. Strong room temperature luminescence was observed under 514.5 nm Ar-laser pumping. Two-lifetime (3.0 and 6.0 ms) luminescent decay is characteristic for the lasing 4I13/2->4I15/2 transition in Er:LiNbO3 films. PMID- 22297373 TI - Fringe pattern denoising via image decomposition. AB - Filtering off noise from a fringe pattern is one of the key tasks in optical interferometry. In this Letter, using some suitable function spaces to model different components of a fringe pattern, we propose a new fringe pattern denoising method based on image decomposition. In our method, a fringe image is divided into three parts: low-frequency fringe, high-frequency fringe, and noise, which are processed in different spaces. An adaptive threshold in wavelet shrinkage involved in this algorithm improves its denoising performance. Simulation and experimental results show that our algorithm obtains smooth and clean fringes with different frequencies while preserving fringe features effectively. PMID- 22297374 TI - Effect of emitter number on quantum cascade laser monolithic phased array. AB - We present the optical analysis of spatial single-mode monolithic quantum cascade laser arrays in the mid-IR. Subwavelength parallel microstripe waveguides are buried into InP:Fe and phase locked by evanescent coupling. Lasing at room temperature is obtained at lambda=8.4 MUm. We describe the near- and far-field of stripe arrays comprising up to 32 emitters. One hundred percent coherent emission is shown experimentally and well accounted for by a standard optical simulation. PMID- 22297375 TI - Evolution of 3D degrees of polarization with random unitary transformations. AB - The irreversible behavior of polarization properties that appears when random unitary transformations are applied to three-dimensional (3D) random optical fields is investigated. The ability of 3D degrees of polarization not to increase and to evolve independently of each other with such transformations is analyzed. PMID- 22297376 TI - Stimulated Raman hyperspectral imaging based on spectral filtering of broadband fiber laser pulses. AB - We demonstrate a technique of hyperspectral imaging in stimulated Raman scattering (SRS) microscopy using a tunable optical filter, whose transmission wavelength can be varied quickly by a galvanometer mirror. Experimentally, broadband Yb fiber laser pulses are synchronized with picosecond Ti:sapphire pulses, and then spectrally filtered out by the filter. After amplification by fiber amplifiers, we obtain narrowband pulses with a spectral width of <3.3 cm( 1) and a wavelength tunability of >225 cm(-1). By using these pulses, we accomplish SRS imaging of polymer beads with spectral information. PMID- 22297377 TI - Sub-nano resolution fiber-optic static strain sensor using a sideband interrogation technique. AB - We propose a novel sideband interrogation technique with multiplex radio frequency intensity and phase modulation to measure the resonance frequency difference between two optical resonators. Based on this new technique, an ultrahighly sensitive fiber-optic static strain sensor system consisting of a pair of identical fiber Fabry-Perot interferometers is built by incorporating a cross-correlation data processing algorithm. A static strain resolution down to 0.8 nepsilon is demonstrated experimentally, which makes the sensor system a useful tool for geophysical research applications. PMID- 22297378 TI - Passively mode locked femtosecond Tm:Sc2O3 laser at 2.1 MUm. AB - We report on the passive mode locking of a Tm3+:Sc2O3 laser at 2.1 MUm using a semiconductor saturable absorber mirror based on InGaAsSb quantum wells. Transform-limited 218 fs pulses are generated with an average power of 210 mW. A maximum output power of 325 mW is produced during mode locking with the corresponding pulse duration of 246 fs at a pulse repetition frequency of 124.3 MHz. A Ti:sapphire laser is used as the pump source operating at 796 nm. PMID- 22297379 TI - Oriented imaging of 3D subcellular structures in bacterial cells using optical tweezers. AB - Using oscillating optical tweezers, we show that controlled alignment of rod shaped bacterial cells allows imaging fluorescently labeled three-dimensional (3D) subcellular structures from different, optimized viewpoints. To illustrate our method, we analyze the Z ring of E. coli. We obtain that the radial width of the Z ring in unconstricted cells is about 120 nm. This result suggests that the Z ring consists of an extremely sparse network of FtsZ filaments. PMID- 22297380 TI - Two-step demodulation based on the Gram-Schmidt orthonormalization method. AB - This Letter presents an efficient, fast, and straightforward two-step demodulating method based on a Gram-Schmidt (GS) orthonormalization approach. The phase-shift value has not to be known and can take any value inside the range (0,2pi), excluding the singular case, where it corresponds to pi. The proposed method is based on determining an orthonormalized interferogram basis from the two supplied interferograms using the GS method. We have applied the proposed method to simulated and experimental interferograms, obtaining satisfactory results. A complete MATLAB software package is provided at http://goo.gl/IZKF3. PMID- 22297381 TI - Acute inhibition of iron bioavailability by zinc: studies in humans. AB - Iron (Fe) and zinc (Zn) deficiencies constitute two of the most important nutritional and public health problems affecting developing countries. Combined supplementation or fortification with Zn and Fe are strategies that can be used to improve the Zn and Fe status of a population. However, there is concern about potential negative interactions between these two micronutrients due to a competitive binding to DMT1 and Zip14 transporter. Studies performed in humans have shown an inhibitory effect of Zn on Fe absorption when both minerals are given together as a solution in fasting conditions. We found that at low doses of iron (0.5 mg) the threshold for the inhibition of iron bioavailability was at a Zn:Fe wt/wt ratio >=5.9:1, whereas at higher doses of Fe (10 mg) this inhibition occurred at 1:1 Zn:Fe wt/wt ratio. This differential response could be explained by the variation in the abundance of both cations as they compete for a limited number of shared transporters at the enterocyte. Conflicting results have been obtained when this interaction was studied in different food matrices. A negative interaction was not observed when Fe and Zn were provided in a composite hamburger meal, premature formula, human milk, or cow milk. A decrease on Fe absorption was observed in only 1 of 3 studies when Fe and Zn were supplied in wheat flour. The possibility of a negative interaction should be considered for supplementation or fortification programs with both microminerals. PMID- 22297382 TI - In situ monitoring of a trace intermediate during DNA phosphorylation by T4 polynucleotide kinase for transient kinetic studies. AB - Formation and decomposition of the enzyme-substrate (ES) complex during phosphorylation by T4 polynucleotide kinase (T4 PNK) of dsDNAs were monitored using a highly sensitive quartz crystal microbalance (QCM) to determine kinetic parameters, which were characterised in comparison with those of other enzymes such as DNA polymerase and exo- and endo-nucleases. PMID- 22297383 TI - The role of hydrogen bonding in excited state intramolecular charge transfer. AB - Intramolecular charge transfer (ICT) that occurs upon photoexcitation of molecules is a vital process in nature and it has ample applications in chemistry and biology. The ICT process of the excited molecules is affected by several environmental factors including polarity, viscosity and hydrogen bonding. The effect of polarity and viscosity on the ICT processes is well understood. But, despite the fact that hydrogen bonding significantly influences the ICT process, the specific role of hydrogen bonding in the formation and stabilization of the ICT state is not unambiguously established. Some literature reports predicted that the hydrogen bonding of the solvent with a donor promotes the formation of a twisted intramolecular charge transfer (TICT) state. Some other reports stated that it inhibits the formation of the TICT state. Alternatively, it was proposed that the hydrogen bonding of the solvent with an acceptor favors the TICT state. It is also observed that a dynamic equilibrium is established between the free and the hydrogen bonded ICT states. This perspective focuses on the specific role played by hydrogen bonding of the solvent with the donor and the acceptor, and by proton transfer in the ICT process. The utility of such influence in molecular recognition and anion sensing is discussed with a few recent literature examples in the end. PMID- 22297384 TI - An association account of false belief understanding. AB - The elicited-response false belief task has traditionally been considered as reliably indicating that children acquire an understanding of false belief around 4 years of age. However, recent investigations using spontaneous-response tasks suggest that false belief understanding emerges much earlier. This leads to a developmental paradox: if young infants already understand false belief, then why do they fail the elicited-response false belief task? We postulate two systems to account for the development of false belief understanding: an association module, which provides infants with the capacity to register congruent associations between agents and objects, and an operating system, which allows them to transform these associations into incongruent associations through a process of inhibition, selection and representation. The interaction between the association module and the operating system enables infants to register increasingly complex associations on the basis of another agent's movements, visual perspective and propositional attitudes. This allows us account for the full range of findings on false belief understanding. PMID- 22297385 TI - High-risk prescribing and incidence of frailty among older community-dwelling men. AB - Evidence about the association between treatment with high-risk medicines and frailty in older individuals is limited. We investigated the relationship between high-risk prescribing and frailty at baseline, as well as 2-year incident frailty, in 1,662 men >=70 years of age. High-risk prescribing was defined as polypharmacy (>=5 medicines), hyperpolypharmacy (>=10 medicines), and by the Drug Burden Index (DBI), a dose-normalized measure of anticholinergic and sedative medicines. At baseline, frail participants had adjusted odds ratios (ORs) of 2.55 (95% confidence interval, CI: 1.69-3.84) for polypharmacy, 5.80 (95% CI: 2.90 11.61) for hyperpolypharmacy, and 2.33 (95% CI: 1.58-3.45) for DBI exposure, as compared with robust participants. Of the 1,242 men who were robust at baseline, 6.2% developed frailty over two years. Adjusted ORs of incident frailty were 2.45 (95% CI: 1.42-4.23) for polypharmacy, 2.50 (95% CI: 0.76-8.26) for hyperpolypharmacy, and 2.14 (95% CI: 1.25-3.64) for DBI exposure. High-risk prescribing may contribute to frailty in community-dwelling older men. PMID- 22297386 TI - Regulatory innovation in postmarketing risk assessment and management. AB - The contemporary science of drug safety seeks not only to identify the risks associated with the use of medicines but also to quantify these risks, identify their risk factors, and assess strategies to minimize them. It monitors the use of medicines in actual practice to understand how the medical care system interacts with the intrinsic pharmacologic properties of medicines to produce the observed effects. To the extent possible, these analyses use a population-based approach that at times requires creativity and innovation. The key to effective safety management of drugs in the postmarketing setting is the ability to access sufficient good-quality data, interpret the data appropriately, challenge old assumptions, and define best practices in contemporary drug safety approaches. PMID- 22297387 TI - Impact of efavirenz on intestinal metabolism and transport: insights from an interaction study with ezetimibe in healthy volunteers. AB - Hypercholesterolemia frequently occurs in patients treated with efavirenz who cannot be treated adequately with statins because of drug interactions. These patients may benefit from cholesterol-lowering therapy with ezetimibe. This study determined the influence of single-dose and multiple-dose efavirenz (400 mg/day for 9 days) on the pharmacokinetics and sterol-lowering of ezetimibe (10 mg) in 12 healthy subjects. In addition, the influence of efavirenz on genome-wide intestinal expression and in vitro function of ABCB1, ABCC2, UGT1A1, and OATP1B1 was studied. Efavirenz (multiple dose) had no influence on the pharmacokinetics and lipid-lowering functions of ezetimibe. Intestinal expression of enzymes and transporters (e.g., ABCB1, ABCC2, and UGT1A1) was not affected by chronic efavirenz. Efavirenz (single dose) slightly increased ezetimibe absorption and markedly decreased exposure to ezetimibe-glucuronide (single dose and multiple dose), which may be explained by inhibition of UGT1A1 and ABCB1 (in vitro data). Ezetimibe had no effect on the disposition of efavirenz. Consequently, ezetimibe may be a safe and efficient therapeutic option in patients with HIV infection. PMID- 22297388 TI - Association between 12p13 SNPs rs11833579/rs12425791 near NINJ2 gene and ischemic stroke in East Asian population: evidence from a meta-analysis. AB - BACKGROUND: Meta-analysis in European population found no association between rs12425791/rs11833579 and ischemic stroke. Several studies focused on East Asians have evaluated the association between this two SNPs and risk of ischemic stroke, but the results have been inconsistent. The aim of this study was to perform a meta-analysis to investigate a more authentic association between rs12425791 and rs11833579 G>A mutation and ischemic stroke in East Asian population, as well as in Chinese Han population. METHODS: Systematic searches of electronic databases Embase, PubMed, Web of Science, and CBM as well as hand searching of the references of identified articles and the meeting abstracts were performed. Study selection, data abstraction and study quality evaluation were independently conducted in duplicate. Statistical analyses were performed using software Stata 11.0. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were performed. Different effects models were used according to the difference in heterogeneity. Publication bias was tested by Begg's funnel plot and Egger's regression test. RESULTS: A total of 4 publications including 7 studies were involved. For rs12425791, significant association was found in allelic model (OR=1.06, 95%CI=1.00-1.11) and dominant model (OR=1.10, 95%CI=1.03-1.18), whereas no evidence of association was found for additive model (OR=1.04, 95%CI=0.93 1.17) and for recessive model (OR=0.99, 95%CI=0.88-1.10). For rs11833579, no evidence of association was found for all genetic models. In the analysis of Chinese Han population, there is lack of evidence for association of ischemic stroke for both SNPs. CONCLUSIONS: In summary, our meta-analysis suggests that rs12425791 is significantly associated with ischemic stroke in East Asian population but not Chinese Han population, of which A alleles increase the risk of ischemic stroke, whereas no evidence of association was found for rs11833579 in East Asian population as well as Chinese Han population. PMID- 22297389 TI - IOM issues report on breast cancer and the environment. PMID- 22297390 TI - Synthesis, characterization, DNA binding and cleavage studies of mixed-ligand Cu(II) complexes of 2,6-bis(benzimidazol-2-yl)pyridine. AB - Four novel copper(II) complexes of the composition [CuLX] where L = 2,6 bis(benzimidazole-2yl)pyridine, X = dipyridophenazine (L1), 1,10-phenanthroline (L2), hydroxyproline (L3) and 2,6-pyridine dicarboxylic acid (L4) were synthesized and characterized by using elemental analysis, FT-IR, UV-vis, ESI-MS, molar conductance and magnetic susceptibility measurements. The complexes [CuLL1](NO3)2 [1], [CuLL2](NO3)2 [2], [CuLL3](NO3) [3] and [CuLL4] (NO3) [4] are stable at room temperature. In DMSO the complexes [1] and [2] are 1:2 electrolytes, [3] and [4] are 1:1 electrolytes. Based on elemental and spectral studies five coordinated geometry is assigned to all the four complexes. The interaction of four copper ion complexes with calf thymus DNA were carried out by UV-vis titrations, fluorescence spectroscopy, thermal melting and viscosity measurements .The binding constant (K(b)) of the above four metal complexes were determined as 5.43 * 10(4) M(-1), 2.56 * 10(4) M(-1), 1.21 * 10(4) M(-1) and 1.57 * 10(4) M(-1) respectively. Quenching studies of the four complexes indicates that these complexes strongly bind to DNA, out of all complex 1 is binding more strongly. Viscosity measurements indicate the binding mode of complexes with CT DNA by intercalation through groove. Thermal melting studies also support intercalative binding. The nuclease activity of the above metal complexes shows that 1, 2 and 3 complexes cleave DNA through redox chemistry. PMID- 22297391 TI - Accumulation of drug resistance and loss of therapeutic options precede commonly used criteria for treatment failure in HIV-1 subtype-C-infected patients. AB - BACKGROUND: Virological monitoring is essential to identify antiretroviral treatment (ART) failure, but not widely available. Here, accumulation of resistance and consequences for second-line therapy were investigated in African HIV-1 subtype-C-infected patients. METHODS: A total of 836 patients initiated non nucleoside reverse transcriptase inhibitor (NNRTI)-based ART and received biannual HIV RNA monitoring. When first-line ART was continued despite virological failure (HIV RNA>1,000 copies/ml), genotypic resistance analysis was performed at baseline, first failure (t1), and 6 or 12 months later (t2). Major resistance mutations (IAS), Stanford genotypic sensitivity scores (GSSs) and proportions of patients meeting WHO-defined failure criteria were compared between time points. RESULTS: Most patients (642/836, 77%) reached viral suppression and 145/642 patients (23%) experienced subsequent failure after a median of 18 months. Counselling resulted in virological re-suppression in 27% (39/145) and 40% (58/145) continued first-line ART despite virological failure; 26 patients were included for genotypic analysis.The mean number of major drug resistance mutations per person increased from 2.8 (t1) to 4.3 (t2). Initially, NNRTI-associated mutations (n=47) predominated; only 25 nucleoside reverse transcriptase inhibitor (NRTI)-associated mutations (mainly M184V) were detected. During prolonged viraemia, NRTI resistance increased (n=44, +76%), in particular thymidine analogue mutations (from 4 to 14) and K65R (from 3 to 6). Consequently, GSSs declined from baseline to t1 and t2: from 3.8 to 1.0 to 0.7 (NNRTIs) and from 6.8 to 5.1 to 4.0 (NRTIs). Despite broad resistance, immunological failure was limited at t2. CONCLUSIONS: Rapid accumulation of drug resistance occurred when ART was continued despite virological failure. Treatment options were lost, even when WHO-defined failure criteria were not met. This study calls for wider access to virological monitoring. PMID- 22297392 TI - Functional characterization of the Gentiana lutea zeaxanthin epoxidase (GlZEP) promoter in transgenic tomato plants. AB - The accumulation of carotenoids in plants depends critically on the spatiotemporal expression profiles of the genes encoding enzymes in the carotenogenic pathway. We cloned and characterized the Gentiana lutea zeaxanthin epoxidase (GlZEP) promoter to determine its role in the regulation of carotenogenesis, because the native gene is expressed at high levels in petals, which contain abundant chromoplasts. We transformed tomato (Solanum lycopersicum cv. Micro-Tom) plants with the gusA gene encoding the reporter enzyme beta glucuronidase (GUS) under the control of the GlZEP promoter, and investigated the reporter expression profile at the mRNA and protein levels. We detected high levels of gusA expression and GUS activity in chromoplast-containing flowers and fruits, but minimal levels in immature fruits containing green chloroplasts, in sepals, leaves, stems and roots. GlZEP-gusA expression was strictly associated with fruit development and chromoplast differentiation, suggesting an evolutionarily-conserved link between ZEP and the differentiation of organelles that store carotenoid pigments. The impact of our results on current models for the regulation of carotenogenesis in plants is discussed. PMID- 22297393 TI - Vibrational energy redistribution in catechol during ultraviolet photolysis. AB - This article reports the striking interplay between the molecular structure and the photodissociation dynamics of catechol (a key dihydroxybenzene), identified using a combination of electronic spectroscopy, hydrogen (Rydberg) atom photofragment translational spectroscopy, density functional theory and second order approximate coupled cluster methods. We describe how the non-planar (C(1) symmetry) <- planar (C(s) symmetry) geometry change during S(1) (1(1)pipi*) < S(0) excitation in catechol, as well as the presence of internal hydrogen bonding, can perturb the photodissociation dynamics relative to that of phenol (a monohydroxybenzene), particularly with respect to O-H bond fission via the lowest dissociative (1)pisigma* state. For lambda(phot) > 270 nm, O-H bond fission (of the non hydrogen bonded hydroxyl moiety) is deduced to proceed via H atom tunnelling from the photo-prepared 1(1)pipi* state into the lowest (1)pisigma* state of the molecule. The vibrational energy distribution in the resulting catechoxyl product changes notably as lambda(phot) is tuned on resonance with either the v' = 0, m(2)' = 1(+) or m(2)' = 2(+) torsional levels of the photo prepared 1(1)pipi* state: the product state distribution is highly sensitive to the degree of OH torsional excitation (m(2)) prepared during photo-excitation. It is deduced that such torsional excitation can be redistributed very efficiently into ring puckering (and likely also in-plane ring stretch) vibrations as the molecule tunnels to its repulsive 1(1)pisigma* state and dissociates. These observations can be rationalised by consideration of the photo-prepared nuclear wavefunctions. Analysis of the product vibrational energy distribution also reveals that the O-H bond strength of the non hydrogen bonded O-H moiety in catechol, D(0)(H-catechoxyl) <= 27 480 +/- 50 cm(-1), ~2500 cm(-1) lower than that of the sole O-H bond in bare phenol. As a consequence, the vertical excitation energy of the 1(1)pisigma* state in catechol is reduced relative to that in phenol, yielding a particularly broad distribution of product vibrations for lambda(phot) < 270 nm. This study highlights the interplay between molecular geometry and redistribution of vibrational energy during ultraviolet photolysis of phenols. PMID- 22297394 TI - One-dimensional ferromagnetic dendritic iron wire array growth by facile electrochemical deposition. AB - One-dimensional ferromagnetic iron dendritic wire array film is prepared by facile electrodeposition. The space hindrance effect caused by neighbouring crystals resists the free growth directions parallel to the substrate, which is considered as a possible growth mechanism of one-dimensional morphology. Dendritic iron wire can be transformed into alpha-Fe(2)O(3) without destroying the dendritic morphology by thermal oxidation. PMID- 22297395 TI - Rotating cell culture systems for human cell culture: human trophoblast cells as a model. AB - The field of human trophoblast research aids in understanding the complex environment established during placentation. Due to the nature of these studies, human in vivo experimentation is impossible. A combination of primary cultures, explant cultures and trophoblast cell lines support our understanding of invasion of the uterine wall and remodeling of uterine spiral arteries by extravillous trophoblast cells (EVTs), which is required for successful establishment of pregnancy. Despite the wealth of knowledge gleaned from such models, it is accepted that in vitro cell culture models using EVT-like cell lines display altered cellular properties when compared to their in vivo counterparts. Cells cultured in the rotating cell culture system (RCCS) display morphological, phenotypic, and functional properties of EVT-like cell lines that more closely mimic differentiating in utero EVTs, with increased expression of genes mediating invasion (e.g. matrix metalloproteinases (MMPs)) and trophoblast differentiation. The Saint Georges Hospital Placental cell Line-4 (SGHPL-4) (kindly donated by Dr. Guy Whitley and Dr. Judith Cartwright) is an EVT-like cell line that was used for testing in the RCCS. The design of the RCCS culture vessel is based on the principle that organs and tissues function in a three-dimensional (3-D) environment. Due to the dynamic culture conditions in the vessel, including conditions of physiologically relevant shear, cells grown in three dimensions form aggregates based on natural cellular affinities and differentiate into organotypic tissue-like assemblies. The maintenance of a fluid orbit provides a low-shear, low-turbulence environment similar to conditions found in vivo. Sedimentation of the cultured cells is countered by adjusting the rotation speed of the RCCS to ensure a constant free-fall of cells. Gas exchange occurs through a permeable hydrophobic membrane located on the back of the bioreactor. Like their parental tissue in vivo, RCCS-grown cells are able to respond to chemical and molecular gradients in three dimensions (i.e. at their apical, basal, and lateral surfaces) because they are cultured on the surface of porous microcarrier beads. When grown as two-dimensional monolayers on impermeable surfaces like plastic, cells are deprived of this important communication at their basal surface. Consequently, the spatial constraints imposed by the environment profoundly affect how cells sense and decode signals from the surrounding microenvironment, thus implying an important role for the 3-D milieu. We have used the RCCS to engineer biologically meaningful 3-D models of various human epithelial tissues. Indeed, many previous reports have demonstrated that cells cultured in the RCCS can assume physiologically relevant phenotypes that have not been possible with other models. In summary, culture in the RCCS represents an easy, reproducible, high-throughput platform that provides large numbers of differentiated cells that are amenable to a variety of experimental manipulations. In the following protocol, using EVTs as an example, we clearly describe the steps required to three-dimensionally culture adherent cells in the RCCS. PMID- 22297396 TI - Complete electrode model in EEG: relationship and differences to the point electrode model. AB - In electroencephalography (EEG) source analysis, a primary current density generated by the neural activity of the brain is reconstructed from external electrode voltage measurements. This paper focuses on accurate and effective simulations of EEG through the complete electrode model (CEM). The CEM allows for the incorporation of the electrode size, shape and effective contact impedance into the forward simulation. Both neural currents in the brain and shunting currents between the electrodes and the skin can affect the measured voltages in the CEM. The goal of this study was to investigate the CEM by comparing it with the point electrode model (PEM), which is the current standard electrode model for EEG. We used a three-dimensional, realistic and high-resolution finite element head model as the reference computational domain in the comparison. The PEM could be formulated as a limit of the CEM, in which the effective impedance of each electrode goes to infinity and the size tends to zero. Numerical results concerning the forward and inverse errors and electrode voltage strengths with different impedances and electrode sizes are presented. Based on the results obtained, limits for extremely high and low impedance values of the shunting currents are suggested. PMID- 22297397 TI - L-N-iminoethyl-lysine after experimental brain trauma attenuates cellular proliferation and astrocyte differentiation. AB - BACKGROUND: The effects, and thereby possible benefit, of inhibiting nitric oxide synthases (NOS) after brain injury are not fully understood. Nitric oxide (NO) has both neuroprotective and damaging features, and its effect on the cellular proliferation and differentiation that occurs in response to traumatic brain injury (TBI) is largely unknown. This study was undertaken to investigate the effects of the selective inducible NOS-inhibitor, L-N-iminoethyl-lysine (L-NIL), on proliferating cell populations in rat brain areas with self-renewing capacity. METHODS: A brain contusion was produced using a weight-drop model in rats. Animals received treatment with L-NIL or saline, and were killed after 6 days. Brain sections were stained with a cell marker of proliferation, Ki67, to detect dividing cells in the hippocampus, perilesional zone and the subventricular zone (SVZ). RESULTS: A significant decrease of proliferating cells was seen in the SVZ bilaterally in L-NIL-treated animals compared to controls. Hippocampal proliferation showed a tendency to decrease in L-NIL-treated animals that did not reach statistical significance. Perilesional proliferation was equal in the treatment group and controls. The percentage of proliferating GFAP expressing cells was, however, lower in L-NIL-treated animals. The proliferating cell populations were predominantly immunoreactive for GFAP, while a smaller population was immunoreactive for Nestin. The inhibition of inducible NOS with L NIL attenuated the level of cellular proliferation and influenced the differentiation of astrocytes at 6 days after experimental brain contusion. CONCLUSIONS: Our results confirmed that reactive glial cells dominated the proliferating cell population after TBI and suggested that NO-regulated mechanisms are relevant for post-traumatic cellular proliferation and differentiation, since NO inhibition decreased the number of proliferating cells in the SVZ and the proportion of proliferating cells expressing GFAP, a marker of glial proliferation. PMID- 22297398 TI - The relation between zoledronic acid infusion and interbody fusion in patients undergoing transforaminal lumbar interbody fusion surgery. AB - BACKGROUND: Zoledronic acid (ZOL) has been shown to significantly increase bone mineral density and to decrease the incidence of osteoporotic fractures. However, its safety when used after lumbar interbody fusion surgery remains unclear. We sought to determine whether ZOL infusion 3 days after transforaminal lumbar interbody fusion (TLIF) affects the risk of nonunion. METHODS: This was a randomized, double-blind, placebo-controlled trial involving subjects who underwent TLIF surgery. Eighty-two subjects (>=50 years of age) were randomly assigned to receive either 5 mg intravenous ZOL (N=41) or placebo (N=41) 3 days after surgery. Each patient received a lumbar computed tomography scan 6 months and 12 months postoperatively. We evaluated interbody fusion using the multiplanar reconstruction technique. Clinical outcome was evaluated with the Oswestry Disability Index. Bone turnover markers (amino terminal propeptides of type I collagen and C-telopeptide of type I collagen) were measured to investigate the biological effects of ZOL on spinal fusion. RESULTS: In the ZOL group, 7 levels (11.5%) exhibited non-union; in the placebo group, 9 levels (14.5%) exhibited nonunion at 12 months postoperatively. This difference was not statistically significant (P=0.82). The difference in ODI scores between two groups was not statistically significant at any of the follow-up times. However, ZOL decreased bone turnover markers significantly. CONCLUSIONS: There was no association between ZOL treatment and nonunion of the lumbar spinal bone. Thus, undergoing lumbar interbody fusion surgery is not a valid reason to suspend or avoid treatment with ZOL. PMID- 22297399 TI - 5-Aminolevulinic acid-induced protoporphyrin IX fluorescence as immediate intraoperative indicator to improve the safety of malignant or high-grade brain tumor diagnosis in frameless stereotactic biopsies. AB - BACKGROUND: Frameless stereotactic biopsies are replacing frame-based stereotaxy as a diagnostic approach to brain lesions. In order to avoid a sampling bias or negative histology, multiple specimens are often taken. This in turn increases the risk of hemorrhagic complications. OBJECTIVE: We present the use of 5 aminolevulinic acid (5-ALA)-induced protoporphyrin IX fluorescence in frameless stereotaxy to improve the procedure duration and yield, and thereby reduce the risk of complications. METHODS: Patients with suspected high-grade brain tumors are given 5-ALA 4 h prior to stereotactic biopsy. The biopsy needle is guided to the target using frameless stereotaxy based either on preoperative images or combined with intraoperative MRI sequences. The specimen is illuminated with blue light to look for fluorescence. In case of a positive fluorescence within the tissue sample, no frozen sections are obtained, and no further specimens are taken. RESULTS: The samples of 13 patients revealed a positive fluorescence and were histologically confirmed as malignant or high-grade brain neoplasms. four cases were fluorescence-negative, requiring frozen section confirmation and/or multiple samples. In theses cases histology was either nonspecific gliotic changes or low-grade tumors. There were no complications related to the additional use of 5-ALA. CONCLUSION: 5-ALA fluorescence in stereotactic biopsies can increase the safety and accuracy of these procedures by reducing sampling errors and eliminating the need for multiple samples and/or frozen section verification, creating a more accurate, faster and safer procedure for cases of suspected malignant or high-grade brain tumors situated in deep or eloquent areas. PMID- 22297400 TI - Socio-economic disparities in mortality due to pandemic influenza in England. AB - OBJECTIVES: This study examines variations in mortality between socio-economic groups due to the pandemic Influenza (H1N1) 2009 virus in England. METHODS: We established a system to identify all deaths related to pandemic (H1N1) 2009 influenza. We collected the postcode of every individual who died, and through this determined the socio-economic deprivation, urban-rural characteristics and region of their residence. Across England, we were therefore able to examine how mortality rates varied by socio-economic group, between urban and rural areas, and between regions. RESULTS: People in the most deprived quintile of England's population had an age and sex-standardised mortality rate three times that experienced by the least deprived quintile (RR = 3.1, 95% CI 2.2-4.4). Mortality was also higher in urban areas than in rural areas (RR = 1.7, 95% CI 1.2-2.3). Mortality rates were similar between regions of the country. CONCLUSION: Tackling socio-economic health inequalities is a central concept within public health, but has not always been a part of emergency preparedness plans. These data demonstrate the opportunity to reduce the overall impact and narrow inequalities by considering socio-economic disparities in future pandemic planning. PMID- 22297401 TI - Could the canopy structure of bryophytes serve as an indicator of microbial biodiversity? A test for testate amoebae and microcrustaceans from a subtropical cloud forest in Dominican Republic. AB - The mechanisms that ultimately regulate the diversity of microbial eukaryotic communities in bryophyte ecosystems remain a contentious topic in microbial ecology. Although there is robust consensus that abiotic factors, such as water chemistry of the bryophyte and pH, explain a significant proportion of protist and microcrustacean diversity, there is no systematic assessment of the role of bryophyte habitat complexity on such prominent microbial groups. Water-holding capacity is correlated with bryophyte morphology and canopy structure. Similarly, canopy structure explains biodiversity dynamics of the macrobiota suggesting that canopy structure may also be a potential parameter for understanding microbial diversity. Canopy roughness of the dominant bryophyte species within the Bahoruco Cloud Forest, Cachote, Dominican Republic, concomitant with their associated diversity of testate amoebae and microcrustaceans was estimated to determine whether canopy structure could be added to the list of factors explaining microbial biodiversity in bryophytes. We hypothesized that smooth (with high moisture content) canopies will have higher species richness, density, and biomass of testate amoebae and higher richness and density of microcrustaceans than rough (desiccation-prone) canopies. For testate amoebae, we found 83 morphospecies with relative low abundances. Species richness and density differed among bryophytes with different bryophyte canopy structures and based on non metric multidimensional scaling, canopy roughness explained 25% of the variation in species composition although not as predicted. Acroporium pungens (low roughness, LR) had the lowest species richness (2 +/- 0.61 SD per gram dry weight bryophyte), and density (2.1 +/- 0.61 SD individual per gram of dry weight bryophyte); whereas Thuidium urceolatum (high roughness) had the highest richness (24 +/- 10.82 SD) and density (94 +/- 64.30 SD). The fact that the bryophyte with the highest roughness had the highest levels of diversity for testate amoebae suggests that moisture levels at the level of the bryophyte canopy may not represent a biodiversity driver in a cloud forest with high relative humidity; however, high roughness could generate a dynamic and fluctuating moisture environment with concomitant alternating microbial communities. A total of 26 microcrustacean morphospecies were found across 11 bryophytes; however, no bryophyte canopy effect was detected on their richness and density. Microcrustacean mean density was low ranging from less than one individual per 50 cm2 of bryophyte in Leucobryum (LR) to a maximum of 6 +/- 3.37 SD individuals/50 cm2 in Monoclea (LR). This lack of pattern suggests that possible explanatory variables may be related to larger scale processes than those examined in this study. PMID- 22297402 TI - Cost-effective large-scale synthesis of ZnO photocatalyst with excellent performance for dye photodegradation. AB - Zinc oxide with excellent photocatalytic performance for the photodegradation of dyes (superior to Degussa P25 TiO(2)) could be easily prepared in large quantity by direct calcination of zinc acetate (Zn(Ac)(2).2H(2)O). PMID- 22297410 TI - Internet use by parents of infants with positive newborn screens. AB - BACKGROUND: Internet searches on health topics are common, but not enough is known about online use during serious health concerns. The aim of this study was to investigate parents' internet use and responses to online information following the referral of their newborn screen-positive infants. METHODS: Forty four parents were interviewed about their internet use during their infants' evaluations for a potential metabolic disorder. Responses to open-ended questions were audio taped and transcribed. Content analysis was used in analyzing the interview data. RESULTS: An overwhelming majority of parents (89%) accessed the internet and most went online before meeting with genetic providers at metabolic treatment centers. Primary and genetic providers did not routinely recommend websites to parents. Online descriptions of metabolic disorders increased parents' anxieties. Some parents allayed their distress by enlisting others to search and filter information for them and by seeking optimistic internet content about the disorders. Parents with fewer years of education were often baffled by complex disease information. Parents found limited information about treatments or what to expect during the clinical evaluations of their infants. CONCLUSIONS: The internet is an integral part of health care and an important source of information for newborn screening parents. Parents may benefit from recommendations of credible websites and discussions of internet information with health care providers. PMID- 22297412 TI - Postactivation potentiation: effect of various recovery intervals on bench press power performance. AB - Postactivation potentiation (PAP) is a strategy used to improve performance in power activities. The aim of this study was to determine if power during bench press exercise was increased when preceded by 1 repetition maximum (1RM) in the same exercise and to determine which time interval could optimize PAP response. For this, 11 healthy male subjects (age, 25 +/- 4 years; height, 178 +/- 6 cm; body mass, 74 +/- 8 kg; bench press 1RM, 76 +/- 19 kg) underwent 6 sessions. Two control sessions were conducted to determine both bench press 1RM and power (6 repetitions at 50% 1RM). The 4 experimental sessions were composed of a 1RM exercise followed by power sets with different recovery intervals (1, 3, 5, and 7 minutes), performed on different days, and determined randomly. Power values were measured via Peak Power equipment (Cefise, Nova Odessa, Sao Paulo, Brazil). The conditions were compared using an analysis of variance with repeated measures, followed by a Tukey test. The significance level was set at p < 0.05. There was a significant increase in PAP in concentric contractions after 7 minutes of recovery compared with the control and 1-minute recovery conditions (p < 0.05). Our results indicated that 7 minutes of recovery has generated an increase in PAP in bench press and that such a strategy could be applied as an interesting alternative to enhance the performance in tasks aimed at increasing upper-body power performance. PMID- 22297413 TI - A reliable method for assessing rotational power. AB - Rotational core training is said to be beneficial for rotational power athletes. Currently, there has been no method proposed for the reliable assessment of rotational power. Therefore, our purpose was to determine the test-retest reliability of kinetic and kinematic rotational characteristics of a pulley system when performing a rotational exercise of the axial skeleton in the transverse plane to find out if this would be a reliable tool for evaluating rotational power. Healthy, college-aged men (n = 8) and women (n = 15) reported for 3 testing sessions. The participants were seated on a box, and they held the handle with both arms extended in front of their body, starting their motion with their torso rotated toward the machine. All the participants rotated their torso forcefully until they reached 180 degrees of rotation, and they then slowly returned to the starting position, 3 times per trial, with 3 loads: 9% body weight (BW), 12% BW, and 15% BW. The repetition with the greatest power for each trial for each load was analyzed. The mean peak power repetition (watts) for all the subjects was 20.09 +/- 7.16 (9% BW), 26.17 +/- 8.6 (12% BW), and 30.74 +/- 11.022 (15% BW) in the first training session and 22.3 +/- 8.087 (9% BW), 28.7 +/ 11.295 (12% BW), and 33.52 +/- 12.965 (15% BW) in the second training session with intraclass correlation coefficients of 0.97 (9%BW), 0.94 (12%BW), and 0.95 (15%BW). When the participants were separated by sex, there were no significant differences between groups. Based on these results, it was found that a pulley system and an external dynamometer can be used together as a reliable research tool to assess rotational power. PMID- 22297414 TI - Energy system contribution to Olympic distances in flat water kayaking (500 and 1,000 m) in highly trained subjects. AB - Olympic flat water kayaking races take place over a distance of 500 and 1,000 m. This study was designed to determine the aerobic and anaerobic contributions to 500- and 1,000-m races during flat water paddling in open water, using the accumulated oxygen deficit (AOD) method. Seven internationally ranked athletes, specialized in 500-m races and familiar with 1,000-m races, participated in this study (age: 21.86 +/- 1.68 years, body mass: 78.54 +/- 3.41 kg, height: 1.84 +/- 0.03 m, body fat%: 10.14 +/- 0.69%). All the participants performed 3 track kayaking sessions. During the first session, the maximal oxygen uptake and maximal aerobic speed were determined using a portable gas analyzer and a global positioning system. During the successive testing sessions, paddlers performed in a randomized counterbalanced order a 500- and a 1,000-m race under field conditions (open water track kayaking). The 500-m AOD was significantly higher than the 1,000-m AOD (18.16 +/- 4.88 vs. 9.34 +/- 1.38 ml.kg(-1), p < 0.05). The aerobic contribution resulted in being higher during the 1,000 m compared with that in the 500-m condition (86.61 +/- 1.86% vs. 78.30 +/- 1.85%, respectively, p < 0.05). The results of this study showed that the 500- and 1,000-m races are 2 physiologically different kayaking events with a higher aerobic contribution in the 1,000 m. The training prescription for elite athletes should emphasize aerobic high-intensity training for the 1,000 m and anaerobic short-term training for the 500-m race. PMID- 22297415 TI - A 10-week stretching program increases strength in the contralateral muscle. AB - It was questioned whether a unilateral stretching program would induce a crosstraining effect in the contralateral muscle. To test this, 13 untrained individuals participated in a 10-week stretching program while 12 other untrained individuals served as a control group. For the experimental group, the right calf muscle was stretched 4 times for 30 seconds, with a 30-second rest between stretches, 3 d.wk(-1) for 10 weeks. Strength, determined via 1 repetition maximum (1RM) unilateral standing toe raise, and range of motion (ROM) were measured pre post. In the treatment group, the stretched calf muscle had a significant (p < 0.05) 8% increase in ROM, whereas the nonstretched calf muscle had a significant 1% decrease in ROM. The 1 RM of the stretched calf muscle significantly increased 29%, whereas the 1RM of the nonstretched calf muscle significantly increased 11%. In the control group, neither 1RM nor ROM changed for either leg. The results indicate that 10 weeks of stretching only the right calf will significantly increase the strength of both calves. Hence, chronic stretching can also induce a crosstraining effect for strength but not for the ROM. This study also validates earlier findings suggesting that stretching can elicit strength gains in untrained individuals. PMID- 22297417 TI - Construction of an infectious cDNA clone of Culex flavivirus, an insect-specific flavivirus from Culex mosquitoes. AB - Culex flavivirus (CxFV) is an insect-specific flavivirus that has recently been detected in various Culex spp. mosquitoes worldwide. Here, we report the successful construction of a full-length infectious cDNA clone of a Tokyo strain, CxFV-NIID21. The full-length CxFV-NIID21 cDNA was cloned into the low-copy-number plasmid pMW119, which was stably amplified in Escherichia coli. Transfection of a mosquito cell line with in vitro-transcribed RNA from the cDNA clone resulted in the production of recombinant progeny virus with growth properties, cytopathogenicity, and virion morphology similar to the parental virus. PMID- 22297418 TI - A finite difference method with periodic boundary conditions for simulations of diffusion-weighted magnetic resonance experiments in tissue. AB - A new finite difference (FD) method for calculating the time evolution of complex transverse magnetization in diffusion-weighted magnetic resonance imaging and spectroscopy experiments is described that incorporates periodic boundary conditions. The new FD method relaxes restrictions on the allowable time step size employed in modeling which can significantly reduce computation time for simulations of large physical extent and allow for more complex, physiologically relevant, geometries to be simulated. PMID- 22297419 TI - Orthogonal protein purification facilitated by a small bispecific affinity tag. AB - Due to the high costs associated with purification of recombinant proteins the protocols need to be rationalized. For high-throughput efforts there is a demand for general methods that do not require target protein specific optimization . To achieve this, purification tags that genetically can be fused to the gene of interest are commonly used. The most widely used affinity handle is the hexa histidine tag, which is suitable for purification under both native and denaturing conditions. The metabolic burden for producing the tag is low, but it does not provide as high specificity as competing affinity chromatography based strategies. Here, a bispecific purification tag with two different binding sites on a 46 amino acid, small protein domain has been developed. The albumin-binding domain is derived from Streptococcal protein G and has a strong inherent affinity to human serum albumin (HSA). Eleven surface-exposed amino acids, not involved in albumin-binding, were genetically randomized to produce a combinatorial library. The protein library with the novel randomly arranged binding surface (Figure 1) was expressed on phage particles to facilitate selection of binders by phage display technology. Through several rounds of biopanning against a dimeric Z domain derived from Staphylococcal protein A, a small, bispecific molecule with affinity for both HSA and the novel target was identified. The novel protein domain, referred to as ABDz1, was evaluated as a purification tag for a selection of target proteins with different molecular weight, solubility and isoelectric point. Three target proteins were expressed in Escherishia coli with the novel tag fused to their N-termini and thereafter affinity purified. Initial purification on either a column with immobilized HSA or Z-domain resulted in relatively pure products. Two-step affinity purification with the bispecific tag resulted in substantial improvement of protein purity. Chromatographic media with the Z-domain immobilized, for example MabSelect SuRe, are readily available for purification of antibodies and HSA can easily be chemically coupled to media to provide the second matrix. This method is especially advantageous when there is a high demand on purity of the recovered target protein. The bifunctionality of the tag allows two different chromatographic steps to be used while the metabolic burden on the expression host is limited due to the small size of the tag. It provides a competitive alternative to so called combinatorial tagging where multiple tags are used in combination. PMID- 22297420 TI - Farm and socio-economic characteristics of smallholder milk producers and their influence on technology adoption in Central Mexico. AB - In order to identify the factors influencing adoption of technologies promoted by government to small-scale dairy farmers in the highlands of central Mexico, a field survey was conducted. A total of 115 farmers were grouped through cluster analysis (CA) and divided into three wealth status categories (high, medium and low) using wealth ranking. Chi-square analysis was used to examine the association of wealth status with technology adoption. Four groups of farms were differentiated in terms of farms' dimensions, farmers' education, sources of incomes, wealth status, management of herd, monetary support by government and technological availability. Statistical differences (p < 0.05) were observed in the milk yield per herd per year among groups. Government organizations (GO) participated little in the promotion of the 17 technologies identified, six of which focused on crop or forage production and 11 of which were related to animal husbandry. Relatives and other farmers played an important role in knowledge diffusion and technology adoption. Although wealth status had a significant association (p < 0.05) with adoption, other factors including importance of the technology to farmers, usefulness and productive benefits of innovations together with farmers' knowledge of them, were important. It is concluded that the analysis of the information per group and wealth status was useful to identify suitable crop or forage related and animal husbandry technologies per group and wealth status of farmers. Therefore the characterizations of farmers could provide a useful starting point for the design and delivery of more appropriate and effective extension. PMID- 22297421 TI - Genotypes of Mycobacterium avium subsp. paratuberculosis from South American countries determined by two methods based on genomic repetitive sequences. AB - Mycobacterium avium subsp. paratuberculosis (MAP) is the causal agent of Johne's disease or paratuberculosis of ruminants and has been associated with Crohn's disease in humans. In this study, the genotypes of MAP obtained so far in South American countries using a combination of the subtyping methods Mycobacterial Interspersed Repeats Units-Variable Number of Tandem Repeats (MIRU-VNTR) and Multilocus Short Sequence Repeats (MLSSR) were analyzed. Through this analysis, seven different MIRU-VNTR genotypes and seven MLSSR genotypes have been detected. If both methods were combined, nine different genotypes were found. Results revealed the predominance of MIRU-VNTR genotype 1 (INMV 1) and MLSSR genotype A (7 g-10 g-4ggt) among MAP isolates from different host species in South America. These predominant MAP genotypes are also commonly detected in Europe and the United States. This predominance could be the result of higher animal infection ability or better culturability on solid media used for isolation. Further studies on molecular epidemiology of MAP must be carried out in South America to increase our knowledge of the global distribution of MAP. PMID- 22297422 TI - Serological and bacteriological responses of water buffalo (Bubalus bubalis) vaccinated with two doses of Brucella abortus strain RB51 vaccine. AB - Thirty-two water buffalo (Bubalus bubalis) calves aged 6-10 months were used to evaluate serological responses to Brucella abortus strain RB51 (RB51) vaccination in a dose-response study and to compare the use of two selective media for the isolation of RB51. The animals were randomly divided into three treatment groups. Groups I-III received the recommended vaccine dose (RD) twice 4 weeks apart, RD twice 18 weeks apart and saline once, respectively. Lymph nodes were excised from the three groups and subjected to bacteriological examination to determine the frequency of detection of RB51. Pre- and post-vaccination blood samples were collected and tested for B. abortus antibodies using the buffered plate agglutination test (BPAT), complement fixation test (CFT), and dot-blot assay. Sera taken at all post-inoculation weeks (PIW) were negative for field strain B. abortus using the BPAT. Antibody responses to RB51 were demonstrated in all vaccinates but not in controls by CFT and dot-blot assay from 1 PIW up to 16 weeks following booster vaccination. The agreement for both assays was 80.7% and there was a linear interdependence with a Pearson's correlation coefficient value of 0.578. The frequency of isolation of RB51 from the two selective media used was not significantly different (P > 0.05). PMID- 22297423 TI - Dietary Wolffia arrhiza meal as a substitute for soybean meal: its effects on the productive performance and egg quality of laying Japanese quails. AB - Wolffia arrhiza meal (WAM) was evaluated as a protein replacement for soybean meal (SBM) in the diet of laying Japanese quails. A total of 480 4-week-old laying quails were randomly allocated to form six groups in a completely randomized design. Each group contained four replicates, with 20 quails per replicate. WAM was incorporated into the diets at levels of 0, 4.00, 8.00, 12.0, 16.0 and 20.0%. The results showed that feed intake per bird per day, daily egg laying rate, feed cost per 100 egg weight, egg width, egg length, egg weight, eggshell thickness, yolk height and shell quality characteristics in terms of breaking time, Young's modulus, work, maximum force, fracturability, breaking stress, stiffness and power showed no statistically significant differences (P > 0.05) among the 0 to 16.0% levels of WAM. However, these performance measures were significantly lower with 20.0% WAM in the formulated ration (P < 0.05). Mortality showed no significant differences among dietary treatments (P > 0.05). The color intensity of the yolk increased as SBM was replaced with increasing amounts of WAM (P < 0.05). In conclusion, WAM could be successfully used in place of SBM. However, the amount used should not exceed 16.0%. PMID- 22297424 TI - Excitation wavelength dependent surface enhanced Raman scattering of 4 aminothiophenol on gold nanorings. AB - Detailed understanding of the underlying mechanisms of surface enhanced Raman scattering (SERS) remains challenging for different experimental conditions. We report on an excitation wavelength dependent SERS of 4-aminothiophenol molecules on gold nanorings. SERS and normal Raman spectra, combined with well characterized surface morphology, optical spectroscopy and electromagnetic (EM) field simulations of gold nanoring substrates indicate that the EM enhancement occurs at all three excitation wavelengths (532, 633 and 785 nm) employed but at short wavelengths (532 and 633 nm) charge transfer (CT) results in additional strong enhancements of particular Raman transitions. These results pave the way to further understanding the origin of the SERS mechanism. PMID- 22297425 TI - Variations in constrained retrieval. AB - Mentally reinstating encoding operations at retrieval might improve access to memories; however, such constrained retrieval is an effortful process that may not always be used. The memory-for-foils procedure (Jacoby, Shimizu, Daniels, & Rhodes, Psychonomic Bulletin & Review 12, 852-857, 2005) infers participant initiated mental reinstatement of encoding operations during attempts at recognition from the differential memory that accrues to foils during a test of deeply processed items versus during a test of shallowly processed items, as indicated by performance on a final recognition memory test for the foils. Experiment 1 tested whether differential memory for foils is due to the evocation of task context during recollection of neighboring old items. Experiment 2 tested whether inducing a set to respond without much effort on a prior recognition test affects the likelihood of constrained retrieval on later tests. Experiment 3 tested whether constrained retrieval is less likely to occur when the deep versus shallow source of test items is intermixed, rather than blocked in separate tests. These experiments provide evidence that people query memory by mentally reinstating encoding operations and identify conditions that affect the probability of constrained retrieval. PMID- 22297426 TI - Population data of 12 X-STR loci in a North of Portugal sample. PMID- 22297427 TI - Non-invasive visualisation and volume estimation of maggot masses using computed tomography scanning. AB - There is limited understanding of the actual temperatures that maggots experience during growth. The impact of maggot mass heating on their growth rates cannot be properly factored into maggot growth rate models, thus limiting the accuracy of forensic entomology estimates. One of the major factors contributing to mass heating is the mass size; however, measuring mass volume is problematic as masses quickly become disturbed when probing them to measure their depth and width. Furthermore, many masses are deep within the body cavity and are inaccessible. This study examined the development of a non-invasive means for measuring mass volume using computed tomography(CT) scanning. It was found that CT can be used to visualise and measure the volume of maggot masses, and a series of rules for doing so were established. The level of agreement between mass measurements made by four 'judges' using CT volumetric analysis tools produced excellent reliability (ICC > 0.95). This high level of reliability was maintained when applied to masses of different sizes in experimental cups of meat and natural masses of mixed species on human bodies. Entomological features of mortuary CT scans are now routinely reported in forensic entomology casework in Victoria, Australia, as a result of our work. PMID- 22297428 TI - The importance of experienced computer tomographic reading in the setting of telemedical stroke management. PMID- 22297429 TI - Deletion of lactate dehydrogenase in Enterobacter aerogenes to enhance 2,3 butanediol production. AB - 2,3-Butanediol is an important bio-based chemical product, because it can be converted into several C4 industrial chemicals. In this study, a lactate dehydrogenase-deleted mutant was constructed to improve 2,3-butanediol productivity in Enterobacter aerogenes. To delete the gene encoding lactate dehydrogenase, lambda Red recombination method was successfully adapted for E. aerogenes. The resulting strain produced a very small amount of lactate and 16.7% more 2,3-butanediol than that of the wild-type strain in batch fermentation. The mutant and its parental strain were then cultured with six different carbon sources, and the mutant showed higher carbon source consumption and microbial growth rates in all media. The 2,3-butanediol titer reached 69.5 g/l in 54 h during fed-batch fermentation with the mutant,which was 27.4% higher than that with the parental strain.With further optimization of the medium and aeration conditions,118.05 g/l 2,3-butanediol was produced in 54 h during fed-batch fermentation with the mutant. This is by far the highest titer of 2,3-butanediol with E. aerogenes achieved by metabolic pathway engineering. PMID- 22297430 TI - Biodiscovery from rare actinomycetes: an eco-taxonomical perspective. AB - Microbial natural products, in particular, the ones produced by the members of the order Actinomycetales, will continue to represent an important route to the discovery of novel classes of bioactive compounds. As a result, the search for and discovery of lesser-known and/or novel actinomycetes is of significant interest to the industry due to a growing need for the development of new and potent therapeutic agents, mainly against drug resistant bacteria. Current advancements in genomics and metagenomics are adding strength to the target directed search for detection and isolation of bioactive actinomycetes. New discoveries, however, will only stem from a sound understanding and interpretation of knowledge derived from conventional studies conducted since the discovery of streptomycin, on the ecology, taxonomy, physiology and metabolism of actinomycetes, and from a combination of this knowledge with currently available and continuously advancing molecular tools. Such a powerful information platform will then inevitably reveal the whereabouts, taxonomical and chemical identities of previously undetected bioactive actinomycetes including novel species of streptomycetes as potential producers of novel drug candidates. PMID- 22297431 TI - Investigating the relationships between peristaltic contraction and fluid transport in the human colon using Smoothed Particle Hydrodynamics. AB - Complex relationships exist between gut contractility and the flow of digesta. We propose here a Smoothed Particle Hydrodynamics model coupling the flow of luminal content and wall flexure to help investigate these relationships. The model indicates that a zone of muscular relaxation preceding the contraction is an important element for transport. Low pressures in this zone generate positive thrust for low viscosity content. The viscosity of luminal content controls the localization of the flow and the magnitude of the radial pressure gradient and together with contraction amplitude they control the transport rate. For high viscosity content, high lumen occlusion is required for effective propulsion. PMID- 22297432 TI - Identification of voltage-gated potassium channel subfamilies from sequence information using support vector machine. AB - Proteins belonging to different subfamilies of Voltage-gated K(+) channels (VKC) are functionally divergent. The traditional method to classify ion channels is more time consuming. Thus, it is highly desirable to develop novel computational methods for VKC subfamily classification. In this study, a support vector machine based method was proposed to predict VKC subfamilies using amino acid and dipeptide compositions. In order to remove redundant information, a novel feature selection technique was employed to single out optimized features. In the jackknife cross-validation, the proposed method (VKCPred) achieved an overall accuracy of 93.09% with 93.22% average sensitivity and 98.34% average specificity, which are superior to that of other two state-of-the-art classifiers. These results indicate that VKCPred can be efficiently used to identify and annotate voltage-gated K(+) channels' subfamilies. The VKCPred software and dataset are freely available at http://cobi.uestc.edu.cn/people/hlin/tools/VKCPred/. PMID- 22297433 TI - Organometallic multiads of zinc(II) porphyrins with interchromophoric cooperativity in S1 and T1 energy transfers. AB - Three different S(1) and T(1) energy donors are linked onto a central zinc(II) porphyrin acceptor and the rates for energy transfers show evidence for cooperativity. PMID- 22297434 TI - Superior reactivity of skeletal Ni-based catalysts for low-temperature steam reforming to produce CO-free hydrogen. AB - This paper describes the utilization of skeletal Ni-based catalysts for steam reforming of ethanol to produce CO-free hydrogen, which could be superior in the application of fuel cells. Assistant metals play different roles in the reaction; Pt and Cu suppress the methanation and enhance H(2) production, while Co promotes the methanation. PMID- 22297435 TI - High-sensitivity CRP in opiate addiction: relative and age-dependent elevations. AB - High-sensitivity C-reactive protein (hs-CRP) has been shown to be linked with immune stimulation, but is not well studied over the lifetime in opiate addiction. hs-CRP was measured by standard laboratory methods in substance use disorder (SUD) patients and non-SUD (NSUD) aged 18-48 years. Data were log transformed to improve normality. 1231 SUD were compared with 326 NSUD patients of comparable ages. hs-CRP was 7.46 +/- 14.24 versus 4.75 +/- 13.40 mg/l (mean +/ SD) significantly higher in the SUD group (P < 0.0001), a difference which persisted after exclusion of acutely elevated hs-CRP values (P < 0.0001). In multiple regression with age, addictive status was significant both by itself (P < 0.0001) and in interaction with age (P < 0.0001). At age 40 years, the SUD group had a mean hs-CRP of 3.68 which the NSUD group did not achieve till a modelled age of 157.09 years. In an interactive multivariate regression, interactions between age, addictive status, ALT and AST were significant. These data show that hs-CRP is elevated in opiate dependence both per se, and when controlled for age. Furthermore, they suggest that hs-CRP and immune stimulation seen in opiate addiction may underlie the acceleration of age-related multi system chronic and coronary atherosclerotic disease well described in opiate dependence. PMID- 22297436 TI - In and out of consciousness: sustained electrophysiological activity reflects individual differences in perceptual awareness. AB - Although significant advances in our understanding of the cognitive and neural processes involved in conscious awareness have occurred in recent years, the precise mechanisms that support consciousness remain elusive. Examining the neural correlates associated with the moment a stimulus enters or exits conscious awareness is one way to potentially identify the neural mechanisms that give rise to consciousness. In the present study, we recorded neural activity using electroencephalography (EEG) while participants observed a bilateral shape-from motion (SFM) display. While the display is in motion, the observer perceives an object that is immediately segregated from a noisy background. After the motion stops, the observer's experience of the object remains momentarily in awareness, before it eventually fades out of consciousness back into the noisy background. Consistent with subjective reports of perceptual experience, we observed a prominent sustained posterior contralateral negativity known as the contralateral delay activity (CDA). This activity was sustained only in conditions associated with sustained awareness. Interestingly, the amplitude of the CDA was correlated with individual differences in visual awareness, suggesting that this activity plays a significant role in the maintenance of objects in consciousness. The CDA is typically associated with visual short-term memory (VSTM), suggesting that conscious visual awareness may be mediated by the same neural and cognitive mechanisms that support VSTM. Our results demonstrate that the CDA may reflect the contents of conscious awareness, and therefore can provide a measure to track when information moves in and out of consciousness. PMID- 22297437 TI - Considerations on ultra-high frequency electric field effects on oxygen vacancy concentration in oxide thin films. AB - Atomistic simulations employing dynamic charge transfer between atoms are used to investigate ultra-thin oxide growth on Al(100) metal substrates in the presence of an ac electric field. In the range of 1-10 GHz frequencies, the enhancement in oxidation kinetics by ~12% over natural oxidation can be explained by the Cabrera Mott mechanism. At field frequencies approaching 0.1-1 THz, however, we observe a dramatic lowering of the kinetics of oxygen incorporation by ~35% compared to the maximum oxidation achieved, which results in oxygen non-stoichiometry near the oxide-gas interface (O/Al ~ 1.0). This is attributed to oxygen desorption from the oxide surface. These results suggest a general strategy to tune oxygen concentration at oxide surfaces using ac electric fields that could be of interest in diverse fields related to surface chemistry and applications such as tunnel barriers, thin dielectrics and oxide interfaces. PMID- 22297438 TI - Immunohistochemical evidence: testicular and scented glandular androgen synthesis in muskrats (Ondatra zibethicus) during the breeding season. AB - In order to elucidate the relationship between androgens and the function of the muskrat (Ondatra zibethicus) scented glands during the breeding season, we investigated immunolocalization of steroidogenic enzymes P450scc, 3betaHSD and P450c17 in the muskrat testes and scented glands. Nine adult muskrats were obtained in March (n=3), May (n=3) and July (n=3) 2010. Steroidogenic enzymes were immunolocalized using polyclonal antisera raised against bovine adrenal P450scc, human placental 3betaHSD and porcine testicular P450c17. Histologically, all types of spermatogenic cells including mature-phase spermatozoa in seminiferous tubules were observed in all testes. Glandular cells, interstitial cells, epithelial cells and excretory tubules were identified in scented glands during the breeding season. P450scc, 3betaHSD and P450c17 were only identified in Leydig cells during the breeding season; P450scc and P450c17 were observed in glandular cells of scented glands, however, 3betaHSD was not found in scented glands during the breeding season. These novel findings provide the first evidence showing that scented glands of the muskrats are capable of locally synthesizing androgens and androgens acting via an endocrine, autocrine or paracrine manner may play an important role in scented gland function during the breeding season. PMID- 22297439 TI - Delayed maturation and altered proliferation within the rat rostral migratory stream following maternal deprivation. AB - The objective of this study was to investigate whether stressful experience during early postnatal period may influence morphological characteristics of the rat neurogenic pathway--the rostral migratory stream (RMS) and proliferation of neuronal precursors in three successive areas of the RMS: in the vertical arm, the elbow and the horizontal arm. To induce stress, the pups were subjected to repeated maternal deprivation during the first postnatal week after birth. Brains were analyzed at the seventh postnatal day. The controls matched the age of maternally deprived animals. Observation of hematoxylin-eosin stained sections showed that maternal deprivation did not affect the general morphological appearance of the RMS. The shape of the RMS of maternally deprived rats resembles the RMS of control animals. Maternal deprivation caused slight, not significant increase in the RMS thickness in comparison with control rats. Significant difference between the control and maternally deprived rats concerns the olfactory ventricle. While in seven days old control rats the olfactory ventricle is completely closed, in maternally deprived rats of the same age the olfactory ventricle was regularly visible as a narrow lumen at the axis of the RMS horizontal arm. This finding indicates delayed maturation of the migratory pathway as a consequence of stress. Proliferation activity has been assessed by immunoreactivity of the endogenous cell cycle protein Ki-67. The results of Ki-67 immunohistochemistry showed that seven days' maternal separation for 3 h daily induces significant quantitative changes in the number of proliferating cells within the RMS. The response of Ki-67-positive cells to stress differed in individual part of the RMS, with a marked decrease in the vertical arm and a significant increase in the elbow, suggesting heterogeneity of neural stem cells along the RMS; while in the RMS vertical arm the number of dividing cells significantly decreased, there was a marked increase of Ki-67-positive cells in the RMS elbow. This suggests heterogeneity of neural stem cells along the RMS. PMID- 22297440 TI - Endothelial cell apoptosis in brown adipose tissue of rats induced by hyperinsulinaemia: the possible role of TNF-alpha. AB - The aim of the present study was to investigate whether hyperinsulinaemia, which frequently precedes insulin resistance syndrome (obesity, diabetes), induces apoptosis of endothelial cells (ECs) in brown adipose tissue (BAT) and causes BAT atrophy and also, to investigate the possible mechanisms underlying ECs death. In order to induce hyperinsulinaemia, adult male rats of Wistar strain were treated with high dose of insulin (4 U/kg, intraperitonealy) for one or three days. Examinations at ultrastructural level showed apoptotic changes of ECs, allowing us to point out that changes mainly but not exclusively, occur in nuclei. Besides different stages of condensation and alterations of the chromatin, nuclear fragmentation was also observed. Higher number of ECs apoptotic nuclei in the BAT of hyperinsulinaemic rats was also confirmed by propidium iodide staining. Immunohistochemical localization of tumor necrosis factor-alpha (TNF-alpha) revealed increased expression in ECs of BAT of hyperinsulinaemic animals, indicating its possible role in insulin-induced apoptotic changes. These results suggest that BAT atrophy in hyperinsulinaemia is a result of endothelial and adipocyte apoptosis combined, rather than any of functional components alone. PMID- 22297441 TI - From chemical neuroanatomy to an understanding of the olfactory system. AB - The olfactory system is the appropriate model for studying several aspects of neuronal physiology spanning from the developmental stage to neural network remodelling in the adult brain. Both the morphological and physiological understanding of this system were strongly supported by classical histochemistry. It is emblematic the case of the Olfactory Marker Protein (OMP) staining, the first, powerful marker for fully differentiated olfactory receptor neurons and a key tool to investigate the dynamic relations between peripheral sensory epithelia and central relay regions given its presence within olfactory fibers reaching the olfactory bulb (OB). Similarly, the use of thymidine analogues was able to show neurogenesis in an adult mammalian brain far before modern virus labelling and lipophilic tracers based methods. Nowadays, a wealth of new histochemical techniques combining cell and molecular biology approaches is available, giving stance to move from the analysis of the chemically identified circuitries to functional research. The study of adult neurogenesis is indeed one of the best explanatory examples of this statement. After defining the cell types involved and the basic physiology of this phenomenon in the OB plasticity, we can now analyze the role of neurogenesis in well testable behaviours related to socio chemical communication in rodents. PMID- 22297442 TI - Autophagic degradation of farnesylated prelamin A as a therapeutic approach to lamin-linked progeria. AB - Farnesylated prelamin A is a processing intermediate produced in the lamin A maturation pathway. Accumulation of a truncated farnesylated prelamin A form, called progerin, is a hallmark of the severe premature ageing syndrome, Hutchinson-Gilford progeria. Progerin elicits toxic effects in cells, leading to chromatin damage and cellular senescence and ultimately causes skin and endothelial defects, bone resorption, lipodystrophy and accelerated ageing. Knowledge of the mechanism underlying prelamin A turnover is critical for the development of clinically effective protein inhibitors that can avoid accumulation to toxic levels without impairing lamin A/C expression, which is essential for normal biological functions. Little is known about specific molecules that may target farnesylated prelamin A to elicit protein degradation. Here, we report the discovery of rapamycin as a novel inhibitor of progerin, which dramatically and selectively decreases protein levels through a mechanism involving autophagic degradation. Rapamycin treatment of progeria cells lowers progerin, as well as wild-type prelamin A levels, and rescues the chromatin phenotype of cultured fibroblasts, including histone methylation status and BAF and LAP2alpha distribution patterns. Importantly, rapamycin treatment does not affect lamin C protein levels, but increases the relative expression of the prelamin A endoprotease ZMPSTE24. Thus, rapamycin, an antibiotic belonging to the class of macrolides, previously found to increase longevity in mouse models, can serve as a therapeutic tool, to eliminate progerin, avoid farnesylated prelamin A accumulation, and restore chromatin dynamics in progeroid laminopathies. PMID- 22297443 TI - Effect of pesticide bendiocarbamate on distribution of acetylcholine- and butyrylcholine-positive nerves in rabbit's thymus. AB - Many pesticides used in agriculture have a negative effect on organisms. The group of hazardous pesticides includes the cholinesterase inhibitor bendiocarbamate. According to literature, bendiocarbamate has relatively low toxicity in mammals and vertebrates in general, since it does accumulate in their tissues and the cholinesterase activity returns to norm within 24 h after acute exposure. The present study focused on the influence of bendiocarbamate on rabbit thymus after its administration at a dose of 5 mg/kg body weight (BW) for the period of 3 months. The thymus was observed for acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)-positive nerve fibers visualized by histochemical methods. Microscopic findings of BuChE-positive nerve fibers show the same density and the topography by the experimental and the control animals. On the other hand, AChE-positive nerve fibers in experimental animals after administration of bendiocarbamate is only poorly identified, suggesting that bendiocarbamate inhibits AChE but not BuChE. PMID- 22297444 TI - Hsp10, Hsp70, and Hsp90 immunohistochemical levels change in ulcerative colitis after therapy. AB - Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) characterized by damage of large bowel mucosa and frequent extra-intestinal autoimmune comorbidities. The role played in IBD pathogenesis by molecular chaperones known to interact with components of the immune system involved in inflammation is unclear. We previously demonstrated that mucosal Hsp60 decreases in UC patients treated with conventional therapies (mesalazine, probiotics), suggesting that this chaperonin could be a reliable biomarker useful for monitoring response to treatment, and that it might play a role in pathogenesis. In the present work we investigated three other heat shock protein/molecular chaperones: Hsp10, Hsp70, and Hsp90. We found that the levels of these proteins are increased in UC patients at the time of diagnosis and decrease after therapy, supporting the notion that these proteins deserve attention in the study of the mechanisms that promote the development and maintenance of IBD, and as biomarkers of this disease (e.g., to monitor response to treatment at the histological level). PMID- 22297445 TI - Nestin expression associates with poor prognosis and triple negative phenotype in locally advanced (T4) breast cancer. AB - Nestin, an intermediate filament protein, has traditionally been noted for its importance as a neural stem cell marker. However, in recent years, expression of nestin has shown to be associated with general proliferation of progenitor cell populations within neoplasms. There is no reported study addressing nestin expression in T4 breast cancer patients. Thus, the aim of the present study was to investigate, through immunohistochemistry, the expression and distribution of nestin in T4 breast cancer, in order to determine its association with clinical and pathological parameters as well as with patients' outcome. Nestin was detectable in tumoral cells and in endothelial cells of blood microvessels, and it is significantly expressed in triple-negative and in inflammatory breast cancer (IBC) subgroups of T4 breast tumours. The Kaplan-Meier analysis showed that the presence of nestin in tumoral cells significantly predicted poor prognosis at 5-years survival (P=0.02) and with borderline significance at 10 years of survival (P=0.05) in T4 breast cancer patients. On the basis of these observations, we speculate that nestin expression may characterize tumours with an aggressive clinical behavior, suggesting that the presence of nestin in tumoral cells and vessels may be considered an important factor that leads to a poor prognosis. Further studies are awaited to define the biological role of nestin in the etiology of these subgroups of breast cancers. PMID- 22297446 TI - Decreased apoptosis in fatty livers submitted to subnormothermic machine perfusion respect to cold storage. AB - Machine perfusion at subnormothermic temperature (20 degrees C), MP20, was developed by Vairetti et al. and showed to afford a better preservation of fatty livers respect to traditional cold storage (CS) in terms of enzyme release into the perfusate and bile, glycogen stores, energy charge and oxidative stress. Here we investigated whether it also caused decreased cell death by apoptosis. Fatty and lean Zucker rats were submitted to MP20 or CS for 6 h and reperfused normothermically for 2 h. Apoptotic cells were revealed by immunohistochemistry of activated caspase-3 and M30 (new epitope on CK18 degraded by caspase-3) and by the TUNEL assay. Portal pressure was also determined. A statistically significant reduction of hepatocyte apoptosis, but especially of sinusoidal cells was determined for fatty livers submitted to MP20 respect to CS. Portal pressure was significantly lower after MP20 respect to CS. The reduction of sinusoidal cell death by apoptosis without need for anti-apoptotic therapies appears particularly positive since apoptotic sinusoidal cells hinder microcirculation in the sinusoids and are thrombogenic. These results further confirm the potential of MP20 for preserving fatty livers that would be otherwise discarded as grafts, and thus for increasing the donor pool for liver transplantation. PMID- 22297447 TI - Embryonic and foetal Islet-1 positive cells in human hearts are also positive to c-Kit. AB - During embryogenesis, the mammalian heart develops from a primitive heart tube originating from two bilateral primary heart fields located in the lateral plate mesoderm. Cells belongings to the pre-cardiac mesoderm will differentiate into early cardiac progenitors, which express early transcription factors which are also common to the Isl-1 positive cardiac progenitor cells isolated from the developing pharyngeal mesoderm and the foetal and post-natal mice hearts. A second population of cardiac progenitor cells positive to c-Kit has been abundantly isolated from adult hearts. Until now, these two populations have been considered two different sets of progenitor cells present in the heart in different stages of an individual life. In the present study we collected embryonic, foetal and infant hearts, and we tested the hypotheses that c-Kit positive cells, usually isolated from the adult heart, are also present in the intra-uterine life and persist in the adult heart after birth, and that foetal Isl-1 positive cells are also positive to c-Kit. Using immunohistochemistry we studied the temporal distribution of Isl-1 positive and c-Kit/CD105 double positive cells, and by immunofluorescence and confocal analysis we studied the co localization of c-Kit and Isl-1 positive cells. The results indicated that cardiomyocytes and interstitial cells were positive for c-Kit from the 9th to the 19th gestational week, that cells positive for both c-Kit and CD105 appeared in the interstitium at the 17th gestational week and persisted in the postnatal age, and that the Isl-1 positive cells were a subset of the c-Kit positive population. PMID- 22297448 TI - Identifying pathological biomarkers: histochemistry still ranks high in the omics era. AB - In recent years, omic analyses have been proposed as possible approaches to diagnosis, in particular for tumours, as they should be able to provide quantitative tools to detect and measure abnormalities in gene and protein expression, through the evaluation of transcription and translation products in the abnormal vs normal tissues. Unfortunately, this approach proved to be much less powerful than expected, due to both intrinsic technical limits and the nature itself of the pathological tissues to be investigated, the heterogeneity deriving from polyclonality and tissue phenotype variability between patients being a major limiting factor in the search for unique omic biomarkers. Especially in the last few years, the application of refined techniques for investigating gene expression in situ has greatly increased the diagnostic/prognostic potential of histochemistry, while the progress in light microscopy technology and in the methods for imaging molecules in vivo have provided valuable tools for elucidating the molecular events and the basic mechanisms leading to a pathological condition. Histochemical techniques thus remain irreplaceable in pathologist's armamentarium, and it may be expected that even in the future histochemistry will keep a leading position among the methodological approaches for clinical pathology. PMID- 22297456 TI - Dietary supplement use by children and adolescents in the United States to enhance sport performance: results of the National Health Interview Survey. AB - Dietary supplements may improve sport performance in adults. However, this has not been established in children. The aim of this study was to assess self reported or parental-reported dietary supplement use to enhance sports performance among the child subset of the National Health Interview Survey (NHIS) dataset and determine national population estimates for that use. NHIS 2007 Child Alternative Medicine files containing records for children aged?18 years were used. Typical demographic variables were utilized as well as parental presence; parental education level; use of any herb, vitamin, and/or mineral use for sports performance by children; and age. Most (94.5%) who reported using supplements used multivitamin and/or mineral combinations followed by fish oil/omega-3 s, creatine, and fiber. Males were more likely users (OR = 2.1; 95% CI [1.3, 3.3]), and Whites reported greater usage. Mean user age was 10.8 (SD = 0.2) with 57.7%[10 years, indicating some increase in use with higher age categories (p?.001). Most were US born and reported living with both parents. Parents and children report child use of a wide variety of herbal and vitamin/mineral supplements to improve sports performance. Usage could be predicted by age, gender, and level of education but less likely by parent-based demographics. PMID- 22297457 TI - Dynamic FDG PET for assessing early effects of cerebral hypoxia and resuscitation in new-born pigs. AB - PURPOSE: Changes in cerebral glucose metabolism may be an early prognostic indicator of perinatal hypoxic-ischaemic injury. In this study dynamic 18F-FDG PET was used to evaluate cerebral glucose metabolism in piglets after global perinatal hypoxia and the impact of the resuscitation strategy using room air or hyperoxia. METHODS: New-born piglets (n = 16) underwent 60 min of global hypoxia followed by 30 min of resuscitation with a fraction of inspired oxygen (FiO2) of 0.21 or 1.0. Dynamic FDG PET, using a microPET system, was performed at baseline and repeated at the end of resuscitation under stabilized haemodynamic conditions. MRI at 3 T was performed for anatomic correlation. Global and regional cerebral metabolic rates of glucose (CMRgl) were assessed by Patlak analysis for the two time-points and resuscitation groups. RESULTS: Global hypoxia was found to cause an immediate decrease in cerebral glucose metabolism from a baseline level (mean +/- SD) of 21.2 +/- 7.9 to 12.6 +/- 4.7 MUmol/min/ 100 g (p <0.01). The basal ganglia, cerebellum and cortex showed the greatest decrease in CMRgl but no significant differences in global or regional CMRgl between the resuscitation groups were found. CONCLUSION: Dynamic FDG PET detected decreased cerebral glucose metabolism early after perinatal hypoxia in piglets. The decrease in CMRgl may indicate early changes of mild cerebral hypoxia ischaemia. No significant effect of hyperoxic resuscitation on the degree of hypometabolism was found in this early phase after hypoxia. Cerebral FDG PET can provide new insights into mechanisms of perinatal hypoxic- ischaemic injury where early detection plays an important role in instituting therapy. PMID- 22297458 TI - PET/MRI in infectious and inflammatory diseases: will it be a useful improvement? PMID- 22297459 TI - Quantitative MRI can detect subclinical disease progression in muscular dystrophy. AB - Oculopharyngeal muscular dystrophy (OPMD) is a rare autosomal dominant muscular dystrophy with late onset and slow progression. The aim of this study was to compare different methods of quantitative MRI in the follow-up of OPMD to semiquantitative evaluation of MRI images and to functional parameters. We examined 8 patients with genetically confirmed OPMD and 5 healthy volunteers twice at an interval of 13 months. Motor function measurements (MFM) were assessed. Imaging at 1.5 T (Siemens Magnetom Avanto) comprised two axial slice groups at the largest diameter of thigh and calf and included T1w TSE, 2-point Dixon for muscular fat fraction (MFF) and a multi-contrast TSE sequence to calculate quantitative T2 values. T1 images were analyzed using Fischer's semiquantitative 5-point (0-4) scale. MFM and visual scores showed no significant difference over the study period. Overall T2 values increased in patients over the study period from 49.4 to 51.6 ms, MFF increased from 19.2 to 20.7%. Neither T2 values nor MFF increased in controls. Changes in T2 correlated with the time interval between examinations (r 2 = 0.42). In this small pilot trial, it was shown that quantitative muscle MRI can detect subclinical changes in patients with OPMD. Quantitative MRI might, therefore, be a useful tool for monitoring disease progression in future therapeutic trials. PMID- 22297460 TI - Neurological deficits in a patient with selenium deficiency due to long-term total parenteral nutrition. PMID- 22297462 TI - Genetic screening of Greek patients with Huntington's disease phenocopies identifies an SCA8 expansion. AB - Huntington's disease (HD) is an autosomal dominant disorder characterized by a triad of chorea, psychiatric disturbance and cognitive decline. Around 1% of patients with HD-like symptoms lack the causative HD expansion and are considered HD phenocopies. Genetic diseases that can present as HD phenocopies include HD like syndromes such as HDL1, HDL2 and HDL4 (SCA17), some spinocerebellar ataxias (SCAs) and dentatorubral-pallidoluysian atrophy (DRPLA). In this study we screened a cohort of 21 Greek patients with HD phenocopy syndromes formutations causing HDL2, SCA17, SCA1, SCA2, SCA3,SCA8, SCA12 and DRPLA. Fifteen patients (71%) had a positive family history. We identified one patient (4.8% of the total cohort) with an expansion of 81 combined CTA/CTG repeats at the SCA8 locus. This falls within what is believed to be the high-penetrance allele range. In addition to the classic HD triad, the patient had features of dystonia and oculomotor apraxia. There were no cases of HDL2, SCA17, SCA1, SCA2, SCA3, SCA12 or DRPLA. Given the controversy surrounding the SCA8 expansion, the present finding may be incidental. However, if pathogenic, it broadens the phenotype that may be associated with SCA8 expansions. The absence of any other mutations in our cohort is not surprising, given the low probability of reaching a genetic diagnosis in HD phenocopy patients. PMID- 22297461 TI - Positron emission tomography imaging in neurological disorders. AB - Positron emission tomography (PET) is a powerful tool for in vivo imaging investigations of human brain function. It provides non-invasive quantification of brain metabolism, receptor binding of various neurotransmitter systems, and alterations in regional blood flow. The use of PET in a clinical setting is still limited due to the high costs of cyclotrons and radiochemical laboratories. However, once these limitations can be bypassed, PET could aid clinical practice by providing a useful imaging technique for the diagnosis, the planning of treatment, and the prediction outcome in various neurological diseases.This review aims to explain the PET imaging technique and its applications in neurological disorders such as Parkinson's disease, Huntington's disease, multiple sclerosis, and dementias. PMID- 22297463 TI - Sir Ludwig Guttmann (1899-1980). PMID- 22297464 TI - Alfred Fuchs (1870-1927). PMID- 22297465 TI - Tin oxide nanowire sensor with integrated temperature and gate control for multi gas recognition. AB - The selectivity of a chemiresistive gas sensor comprising an array of single crystalline tin oxide nanowires (NWs) is shown to be greatly enhanced by combined temperature and gate voltage modulation. This dual modulation was effected by a novel microsensor platform that consisted of a suspended nitride membrane embedded with independently addressable platinum heater and back-gate structures. The sensor was evaluated in a chemical vapor exposure test consisting of three volatile organic compound (VOC) analytes in an air background; VOC concentrations ranged from 20 MUmol/mol to 80 MUmol/mol. During the exposure test, the temperature and gating conditions of the NW sensor were modulated in order to induce variations in the sensor's analyte response behavior. By treating these temperature- and gate-dependent analyte response variations as an identifying "fingerprint," analyte identification was achieved using a statistical pattern recognition procedure, linear discriminant analysis (LDA). Through optimization of this pattern recognition procedure, a VOC recognition rate of 98% was obtained. An analysis of the recognition results revealed that this high recognition rate could only be achieved through the combined modulation of temperature and gate bias as compared to either parameter alone. Overall, the highly accurate VOC analyte discrimination that was achieved here confirms the selectivity benefits provided by the utilized dual modulation approach and demonstrates the suitability of miniature nanowire sensors in real-world, multi chemical detection problems. PMID- 22297466 TI - Utilizing transcranial magnetic stimulation to study the human neuromuscular system. AB - Transcranial magnetic stimulation (TMS) has been in use for more than 20 years, and has grown exponentially in popularity over the past decade. While the use of TMS has expanded to the study of many systems and processes during this time, the original application and perhaps one of the most common uses of TMS involves studying the physiology, plasticity and function of the human neuromuscular system. Single pulse TMS applied to the motor cortex excites pyramidal neurons transsynaptically (Figure 1) and results in a measurable electromyographic response that can be used to study and evaluate the integrity and excitability of the corticospinal tract in humans. Additionally, recent advances in magnetic stimulation now allows for partitioning of cortical versus spinal excitability. For example, paired-pulse TMS can be used to assess intracortical facilitatory and inhibitory properties by combining a conditioning stimulus and a test stimulus at different interstimulus intervals. In this video article we will demonstrate the methodological and technical aspects of these techniques. Specifically, we will demonstrate single-pulse and paired-pulse TMS techniques as applied to the flexor carpi radialis (FCR) muscle as well as the erector spinae (ES) musculature. Our laboratory studies the FCR muscle as it is of interest to our research on the effects of wrist-hand cast immobilization on reduced muscle performance, and we study the ES muscles due to these muscles clinical relevance as it relates to low back pain. With this stated, we should note that TMS has been used to study many muscles of the hand, arm and legs, and should iterate that our demonstrations in the FCR and ES muscle groups are only selected examples of TMS being used to study the human neuromuscular system. PMID- 22297467 TI - Dynamics of the D+ + H2 and H+ + D2 reactions: a detailed comparison between theory and experiment. AB - An extensive set of experimental measurements on the dynamics of the H(+) + D(2) and D(+) + H(2) ion-molecule reactions is compared with the results of quantum mechanical (QM), quasiclassical trajectory (QCT), and statistical quasiclassical trajectory (SQCT) calculations. The dynamical observables considered include specific rate coefficients as a function of the translational energy, E(T), thermal rate coefficients in the 100-500 K temperature range. In addition, kinetic energy spectra (KES) of the D(+) ions reactively scattered in H(+) + D(2) collisions are also presented for translational energies between 0.4 eV and 2.0 eV. For the two reactions, the best global agreement between experiment and theory over the whole energy range corresponds to the QCT calculations using a gaussian binning (GB) procedure, which gives more weight to trajectories whose product vibrational action is closer to the actual integer QM values. The QM calculations also perform well, although somewhat worse over the more limited range of translational energies where they are available (E(T) < 0.6 eV and E(T) < 0.2 eV for the H(+) + D(2) and D(+) + H(2) reactions, respectively). The worst agreement is obtained with the SQCT method, which is only adequate for low translational energies. The comparison between theory and experiment also suggests that the most reliable rate coefficient measurements are those obtained with the merged beams technique. It is worth noting that none of the theoretical approaches can account satisfactorily for the experimental specific rate coefficients of H(+) + D(2) for E(T)<= 0.2 eV although there is a considerable scatter in the existing measurements. On the whole, the best agreement with the experimental laboratory KES is obtained with the simulations carried out using the state resolved differential cross sections (DCSs) calculated with the QCT-GB method, which seems to account for most of the observed features. In contrast, the simulations with the SQCT data predict kinetic energy spectra (KES) considerably cooler than those experimentally determined. PMID- 22297468 TI - Favorable outcome associated with an IGF-1 ligand signature in breast cancer. AB - The insulin-like growth factor (IGF) axis is fundamentally important in cell growth, development and cancer. We used genomic technologies to better characterize the activity of the IGF axis in human breast cancer and to identify predictors of response to IGF targeted therapies. Analysis of the gene expression patterns and pathway analysis in 204 clinically annotated primary breast cancers were performed and compared to levels of mRNA for IGF ligands and receptors. Pathway activation scores were calculated by Pearson correlation (+1, -1). Network analysis was performed using Ingenuity software. IGF-1 ligand levels were strongly negatively correlated (P < 10-6) with a published IGF-IR activation signature.A signature of high IGF-1 ligand was associated with better prognosis (P = 0.025-1.5 x 10-8) in several public datasets. Pathway analysis revealed upregulation of pathways associated with breast differentiation (adipocyte growth factors, PPAR-gamma) and down-regulation of proliferation pathways (AKT/MAPK) in the IGF-1 ligand high group. Of note, the IGF-1 ligand signature was anti correlated with IGFIR receptor levels (P = 0.07). In conclusion, a breast tumor derived signature of high IGF-1 ligand is associated with favorable outcome, in contrast to a previously reported IGF-IR activation signature. The prognostic value of the IGF-I ligand signature is validated in three independent datasets. These signatures should be applied in study of IGF1-R targeted therapy. PMID- 22297469 TI - MUTYH gene variants and breast cancer in a Dutch case-control study. AB - The MUTYH gene is involved in base excision repair. MUTYH mutations predispose to recessively inherited colorectal polyposis and cancer. Here, we evaluate an association with breast cancer (BC), following up our previous finding of an elevated BC frequency among Dutch bi-allelic MUTYH mutation carriers. A case control study was performed comparing 1,469 incident BC patients (ORIGO cohort), 471 individuals displaying features suggesting a genetic predisposition for BC, but without a detectable BRCA1 or BRCA2 mutation (BRCAx cohort), and 1,666 controls. First, for 303 consecutive patients diagnosed before age 55 years and/or with multiple primary breast tumors, the MUTYH coding region and flanking introns were sequenced. The remaining subjects were genotyped for five coding variants, p.Tyr179Cys, p.Arg309Cys, p.Gly396Asp, p.Pro405Leu, and p.Ser515Phe, and four tagging SNPs, c.37-2487G>T, p.Val22Met, c.504+35G>A, and p.Gln338His. No bi-allelic pathogenic MUTYH mutations were identified. The pathogenic variant p.Gly396Asp and the variant of uncertain significance p.Arg309Cys occurred twice as frequently in BRCAx subjects as compared to incident BC patients and controls (p=0.13 and p=0.15, respectively). The likely benign variant p.Val22Met occurred less frequently in patients from the incident BC (p=0.03) and BRCAx groups (p=0.11), respectively, as compared to the controls. Minor allele genotypes of several MUTYH variants showed trends towards association with lobular BC histology. This extensive case-control study could not confirm previously reported associations of MUTYH variants with BC, although it was too small to exclude subtle effects on BC susceptibility. PMID- 22297470 TI - A rare case of juvenile acute non-proliferative glomerulonephritis with a 6-year follow-up experience. AB - Juvenile acute non-proliferative glomerulonephritis (JANG) is a relatively new clinico-pathological entity established in 2000. A PubMed search revealed only two published reports encompassing 14 cases of JANG. It is distinguished from acute post-streptococcal glomerulonephritis by the presence of normal serum complement and the absence of diffuse proliferation of mesangial cells in the glomeruli. We report a case of a 4-year-old child that presented with a clinical scenario and renal biopsy findings consistent with JANG. She responded well to treatment with high-dose methylprednisolone for 3 days, followed by gradual taper with oral prednisone. She was monitored closely for a period of 6 years and continues to do well with normal renal parameters and without any medications. PMID- 22297471 TI - A comparison of digitized frozen section and smear preparations for intraoperative neurotelepathology. AB - BACKGROUND: Intraoperative consultations in neuropathology are often assessed by smear preparations rather than by frozen sections. Both techniques are standard practice for light microscopic examination on site, but there is little data comparing these techniques in a telepathology setting. METHODS: Thirty cases of brain tumours submitted for intraoperative consultation at our institution between July and December 2010 were identified in which both frozen section and tissue smear preparations were available for digitization at 20* magnification. Slides were digitized using a Hamamatsu Nanozoomer 2.0 HT whole slide scanner, and resulting digital images were visualized at 1680 * 1050 pixel resolution with NDP. view software. RESULTS: The original intraoperative diagnosis was concordant with the sign out diagnosis in 29/30 cases; one tumeur was initially interpreted as a high grade glioma but proved to be a lymphoma at sign out. Digitized frozen section slides were sufficient for diagnosis at 10* magnification in 27/30 cases. Digitized tissue smears were sufficient for diagnosis at 10* magnification in 28/30 cases. In two cases tumour was present on the tissue smear but not the frozen section (one case of recurrent astrocytoma, one case of meningeal carcinomatosis). In one case of lymphoma, tumour was present on frozen section only. These discrepancies were attributed to tissue sampling rather than image quality. Examination of digitized slides at higher magnfication (20*) permitted confirmation of mitoses and Rosenthal fibers on tissue smear preparations, but did not change the primary diagnosis. Intra-slide variations in tissue thickness on smear preparations led to variable loss of focus in digitized images, but did not affect image quality in thinner areas of the smear or impede diagnosis. CONCLUSION: Digitized tissue smears are suitable for intraoperative neurotelepathology and provide comparable information to digitized frozen sections at medium power magnification. PMID- 22297472 TI - Virtual microscopy beyond the pyramids, applications of WSI in Cairo University for E-education & telepathology. AB - BACKGROUND: Telepathology, the practice of pathology at a long distance, has advanced continuously since 1986. The progress of telepathology passed through four stages: Static, Dynamic, Hybrid & Whole Slide Imaging. MATERIALS AND METHODS: A pilot project between the Italian Hospital in Cairo & the Civico Hospital in Palermo was completed successfully, applying the static & dynamic techniques of telepathology. This project began in 2003 and continued till now. In 2004, centers in Venice, London and Pittsburgh participated actively in our project. RESULTS: Over eight years we consulted on many problematic pathological cases with specialized pathological centers in Italy, U.K. & U.S.A. In addition to the highly specialized scientific value, we saved a lot of time and money. CONCLUSION: We concluded from our experience that telepathology is a very useful and applicable tool for additional consulting on difficult pathological cases especially for emerging countries. In view of this success we have already established our Digital Telepathology Unit in Cairo University, using the WSI technique in teaching which was greatly successful and encouraged us to build a huge digital pathology library which will expand our telepathology & E-learning programs to cover staff and students in Egypt and Eastern Mediterranean. PMID- 22297473 TI - [Surgical decompression of the lower leg in painful diabetic polyneuropathy]. AB - OBJECTIVE: Surgical decompression of nerves of the lower leg should facilitate swelling-related pressure in diabetic polyneuropathic similar to carpal and cubital tunnel syndrome. Pain reduction, reduced need for pain medication, improved pedal sensitivity, improved balance and proprioception, and potential prevention of ulcerations and amputations are the objectives of the operation. INDICATIONS: Diabetic polyneuropathy with positive Hoffmann-Tinel sign over the tarsal tunnel and an ankle-brachial index >0.7. CONTRAINDICATIONS: No Hoffmann Tinel sign over the tarsal tunnel, no pain, no sensibility disorders, ankle brachial index <0.7, body weight >140 kg. Relative contraindication: venous stasis and postthromobitic syndrome. SURGICAL TECHNIQUE: Under general or spinal anesthesia, tourniquet, decompression of nerves of the lower leg in three locations: (1) common peroneal nerve at the fibula head with incision of the peroneus longus muscle, (2) tarsal tunnel with its four tunnels: (a) tibial nerve in the tarsal tunnel, (b) medial plantar nerve in the medial plantar tunnel, (c) lateral plantar nerve in the lateral plantar tunnel, (d) Rr. calcaneare in the calcaneal tunnel, (3) dorsum of the foot with decompression of the peroneus profundus nerve with excision of the extensor hallucis brevis muscle. POSTOPERATIVE MANAGEMENT: No weight bearing for up to 3 weeks, suture removal after 3 weeks, water aerobics starting postoperative week 4. RESULTS: A total of 12 patients (64+/-9 years) were operated and were followed up for 12+/-6 months. Procedure time was 83+/-27 min. Pain reduction on a visual analogue scale improved from 7.1+/-1.2 preoperatively to 3.3+/-2.4 postoperatively. Balance improved on a Likert scale (1=best, 6=worst) from 5+/-1 to 2+/-1, while sensory impairment improved from 5+/-2 to 3+/-1. There were no ulcerations or amputations. Two secondary wound healing problems at the ankle and one lower leg venous thrombosis 2 weeks following discharge were managed conservatively. PMID- 22297474 TI - [Augmented posterior instrumentation for the treatment of osteoporotic vertebral body fractures]. AB - OBJECTIVE: Reduction and stabilization of osteoporotic vertebral body fractures using posterior short-segment instrumentation. Cement augmentation of the pedicle screws in order to improve the screw's holding power in osteoporotic bone and to reduce postoperative loss of reduction. Quick and painless postoperative mobilization without further bracing. INDICATIONS: Burst fractures (type A3 according to Magerl). Posttraumatic kyphosis following osteoporotic vertebral body fractures. Revision surgery after screw loosening. Type B and C fractures according to Magerl. CONTRAINDICATIONS: Osteoporotic fractures which are suitable for nonoperative treatment or percutaneous cement augmentation techniques (vertebroplasty, kyphoplasty). Vertebral body fractures in patients with good bone quality. SURGICAL TECHNIQUE: Insertion of pedicle screws in a typical manner. If perforated screws are used, cement application under fluoroscopic control via the central perforation of the screws. If pedicle screws without perforation are used, application of the cement using a Kyphoplasty technique and insertion of the screws. After hardening of the cement, completion of the instrumentation. POSTOPERATIVE MANAGEMENT: Mobilization starting on the first day after surgery. Avoidance of heavy lifting and manual labor for 3 months. Implant removal only if it is necessary due to complications. RESULTS: Between July 2008 and December 2009, 10 patients with osteoporotic vertebral body fractures of the thoracic and lumbar spine were treated with cement-augmented posterior instrumentation. The mean age was 65.8 years (range 35-94 years). There were six type A (2 A1 and 4 A3 lesions) and four type B lesions (1 B1, 1 B2, and 2 B3 lesions) according to Magerl. Indications for cement augmentation of the pedicle screws were the patients' age (4 patients), osteoporosis with t scores < - 2.5 (2 patients), poor intraoperative screw hold (2 patients), and revision surgery after loosening of pedicle screws (2 patients). Cement leakage was observed in 5 patients with no further clinical relevance. Loosening of cement augmented pedicle screws occurred in 1 patient with a consecutive loss of reduction of 10 degrees . There was no need to remove any of the cement-augmented screws in the first 24 months. PMID- 22297475 TI - AT2 receptor non-peptide agonist C21 promotes natriuresis in obese Zucker rats. AB - Previously, we demonstrated that angiotensin II type 2 (AT(2)) receptors have a role in natriuresis in obese Zucker rats (OZR). In the present study, we investigated the role of a novel, non-peptide agonist, C21, in natriuresis via AT(2) receptor activation in OZR. Infusion of C21 (1 and 5 MUg kg(-1) min(-1)) into rats under anesthesia caused a dose-dependent increase in urine flow (UF) and urinary Na volume (U(Na)V). These effects of C21 were blocked by pre-infusion of the AT(2) receptor antagonist, PD123319, (50 MUg kg(-1) min(-1)), suggesting involvement of the AT(2) receptor. Infusion of C21 (5 MUg kg(-1) min(-1)) significantly increased the fractional excretion of sodium without changing the glomerular filtration rate or blood pressure, suggesting a tubular effect. Similarly, C21 infusion increased the fractional excretion of lithium, suggesting a proximal tubular effect. Furthermore, we tested the effect of C21 on natriuresis after blocking two main, distal-nephron Na transporters, the epithelial Na channels (ENaC), with amiloride (AM, 3 mg kg(-1) body wt), and the NaCl cotransporters (NCC), with bendroflumethiazide (BFTZ, 7 mg kg(-1) body wt). Infusion of AM + BFTZ caused significant increases in both diuresis and natriuresis, which were further increased by infusion of C21 (5 MUg kg(-1) min( 1)). Natriuresis in response to C21 was associated with increases in urinary NO and cGMP levels. The data indicate that the AT(2) receptor agonist, C21, promotes natriuresis via AT(2) receptor activation and that this effect is potentially based in the proximal tubules and linked to the nitric oxide/cyclic guanosine monophosphate pathway. The natriuretic response to C21 may have therapeutic significance by improving kidney function in obesity. PMID- 22297476 TI - Women are different: the role of coupling factor 6 in blood pressure regulation. PMID- 22297477 TI - Central aortic blood pressure and augmentation index during normal pregnancy. AB - The current study tested the hypothesis that pregnancy-related changes are more pronounced in central hemodynamics, and both central aortic systolic blood pressure (cSBP) and augmentation index (AIx) are independent from brachial systolic blood pressure (bSBP) in normal pregnant subjects. In 830 healthy pregnant women from 12 to 36 weeks gestation, we measured cSBP and AIx-75 (AIx at heart rate of 75 beats per minute) non-invasively by pulse waveforms of the radial artery using an automated applanation tonometric system. In 69 pregnant women, we recorded these data longitudinally. cSBP and AIx-75 significantly declined during pregnancy, reaching its nadir in mid-pregnancy and rising towards term. Pregnancy-related changes were more pronounced in AIx-75 compared with cSBP, but less evident in bSBP. AIx-75, but not cSBP, was independent from bSBP throughout pregnancy. cSBP and AIx-75, but not bSBP, were significantly increased in healthy pregnant women older than 35 years. This study established normal values for pulse wave analysis parameters throughout pregnancy, and indicated that pulse wave analysis might offer additional and independent information about maternal arterial compliance to conventional brachial blood pressure measurements. These data may be used as the basis for further investigation into the role of pulse wave analysis in the assessment, management and prediction of disorders, which might interfere with pregnancy-related cardiovascular adaptations. PMID- 22297478 TI - Hormonal effects on blood vessels. AB - The incidence of cardiovascular disease (CVD) is lower in younger women than in men of the same age, but it increases after menopause, implicating the atheroprotective action of endogenous estrogen. Although observational studies have suggested the efficacy of estrogen therapy in postmenopausal women, placebo controlled, randomized trials, such as the Women's Health Initiative, have not confirmed effects of estrogen therapy on CVD. Conversely, basic, experimental research has progressed and provided mechanistic insight into estrogen's action on blood vessels. By contrast, the vascular effects of androgens remain poorly understood and have been controversial for a long time. In recent years, an increasing body of evidence has suggested that androgens may exert protective effects against the development of atherosclerosis, at least in elderly men. Epidemiological studies have shown that the incidence of and mortality due to CVD were increased in elderly men with low testosterone levels, although the efficacy of androgen therapy remains unknown. Furthermore, recent experimental studies have demonstrated the direct action of androgens on the vasculature. In this review, we illustrate the effects of sex steroids on the cardiovascular system, focusing on the action of testosterone on the blood vessels. PMID- 22297479 TI - Second morning urine method is superior to the casual urine method for estimating daily salt intake in patients with hypertension. AB - The accuracy of the casual urine (CU) method for estimating daily salt intake was compared with the second morning urine (SMU) method and with 24-h urine collection (24 UC) method as the gold standard. Data were obtained from three previously reported studies, in which we evaluated the daily salt intake by the SMU method. Using SMU samples from 1315 outpatients, the estimated salt intake was lower with the CU method than the SMU method. In inpatients with a daily salt intake of 7, 8 or 18 g, the CU method was applied to SMU specimens. It underestimated salt intake compared with the 24-h collection method whereas the SMU method and 24 UC method gave similar results. In the present study, 24 UC was done and then urine was collected at 0800, 1100, 1400, 1700 and 1900 hours, with a daily salt intake of 6 g in 8 inpatients, 10 g in 11 inpatients or 15 g in 5 inpatients. In comparison with the 24 UC method, the CU method underestimated a high salt intake (15 g) when morning specimens were used and overestimated a low salt intake (6 g) when afternoon specimens were used. The correlation between the CU method and 24 UC method was weaker (R = 0.57) than that between the SMU method and 24 UC method (R = 0.85). In conclusion, the CU method is heavily influenced by the timing of urine collection and by the actual daily salt intake, so the SMU method provides a better estimate of individual salt intake. PMID- 22297480 TI - Comparison of two measuring instruments, B-pro and SphygmoCor system as reference, to evaluate central systolic blood pressure and radial augmentation index. AB - A comparison is made of central aortic systolic pressure (CASP) and the radial augmentation index (rAIx) estimated with the B-Pro device and SphygmoCor (as reference) in 104 healthy Caucasians without drug treatment, together with an analysis of the relationship between CASP and rAIx, and arterial stiffness. Peripheral and central blood pressure, and the rAIx were measured with B-pro and SphygmoCor, with determination of the central augmentation index (CAIx), pulse wave velocity (PWV), carotid intima-media thickness (IMT) and the ankle-brachial index (ABI). rAIx as determined with B-Pro was greater than measured with SphygmoCor (5.85; 95%CI: 1.75-9.96), in the same way as CASP, estimated from the transfer function (1.47; 95%CI: 0.47-2.47 mm Hg) and with the second peak of the radial wave (4.46; 95%CI: 2.80-6.12 mm Hg). The Pearson correlation coefficient for CASP with B-Pro and SphygmoCor was r = 0.937 (P < 0.01), with an intraclass correlation of 0.972 (95%CI: 0.959-0.981). In the case of rAIx, the correlation coefficient was r = 0.436 (P < 0.01), with an intraclass correlation of 0.599 (95% CI: 0.409-0.728). The correlation of CASP (B-pro) with PWV was r = 0.558 (P < 0.01), with CAIx r = 0.253 (P < 0.01) and with carotid IMT r = 0.442 (P < 0.01). The correlation of rAIx (B-Pro) with age was r = 0.369 (r < 0.01), and with CAIx r = 0.463 (P < 0.001). Central arterial pressure estimated with B-Pro in healthy Caucasians without drug treatment offers adequate validity vs. the reference standard (SphygmoCor). However, in the estimation of rAIx, some differences with respect to the reference standard have been detected, probably related to measurement of the second peak of the radial wave. PMID- 22297481 TI - Genetic mapping of habitual substance use, obesity-related traits, responses to mental and physical stress, and heart rate and blood pressure measurements reveals shared genes that are overrepresented in the neural synapse. AB - Links between substance use habits, obesity, stress and the related cardiovascular outcomes can be, in part, because of loci with pleiotropic effects. To investigate this hypothesis, we performed genome-wide mapping in 119 multigenerational families from a population in the Saguenay-Lac-St-Jean region with a known founder effect using 58,000 single-nucleotide polymorphisms and 437 microsatellite markers to identify genetic components of the following factors: habitual alcohol, tobacco and coffee use; response to mental and physical stress; obesity-related traits; and heart rate (HR) and blood pressure (BP) measures. Habitual alcohol and/or tobacco users had attenuated HR responses to mental stress compared with non-users, whereas hypertensive individuals had stronger HR and systolic BP responses to mental stress and a higher obesity index than normotensives. Genetic mappings uncovered numerous shared genes among substance use, stress response, obesity and hemodynamic traits, including CAMK4, CNTN4, DLG2, FHIT, GRID2, ITPR2, NOVA1 and PRKCE, forming network of interacting proteins, sharing synaptic function and display higher and patterned expression profiles in brain-related tissues; moreover, pathway analysis of shared genes pointed to long-term potentiation. Subgroup genetic mappings uncovered additional shared synaptic genes, including CAMK4, CNTN5 and DNM3 (hypertension-specific); CNTN4, DNM3, FHIT and ITPR1 (sex-specific), having protein interactions with genes driven from general analysis. In summary, consistent with the observed phenotypic correlations, we found substantial overlap among genomic determinants of these traits in synapse, which supports the notion that the neural synapse may be a shared interface behind substance use, stress, obesity, HR, BP as well as the observed sex- and hypertension-specific genetic differences. PMID- 22297482 TI - D3 dopamine receptor regulation of D5 receptor expression and function in renal proximal tubule cells. AB - Dopamine receptor, via D(1)-like and D(2)-like receptors, increases sodium excretion in kidney. We have reported positive interactions between D(3) and D(1) receptors in renal proximal tubule (RPT) cells. These reports, however do not preclude that there may be also interaction between D(3) and D(5) receptors, because of the lack of selective D(1) and D(5) receptor agonists or antagonists. We hypothesize that D(3) receptors can regulate D(5) receptors, and that D(3) receptor regulation of D(5) receptors in RPTs is impaired in spontaneously hypertensive rats (SHRs). It showed that a D(3) receptor agonist, PD128907, by the activation of protein kinase C activity, increased the expression of D(5) receptors in a concentration- and time-dependent manner in RPT cells from Wistar Kyoto (WKY) rats. The stimulatory effect of the D(3) receptor on D(5) receptor expression was impaired in RPT cells from SHRs. The effect of D(3) receptor on D(5) receptor is functionally relevant; stimulation of D(5) receptor decreases Na(+)-K(+) adenosine triphosphatase (ATPase) activity in WKY cells. Pretreatment with D(3) receptor agonist for 24 h enhances the D(5) receptor expression and D(5) receptor-mediated inhibitory effect on Na(+)-K(+) ATPase activity in WKY cells, but decreases them in SHR cells. The effect of D(3) receptor on D(5) receptor expression and function was also confirmed in the D(5) receptor transfected HEK293 cells. It indicates that activation of D(3) receptor increases D(5) receptor expression and function. Altered regulation of D(3) receptor on D(5) receptors may have a role in the pathogenesis of hypertension. PMID- 22297483 TI - Facile preparation of silicon hollow spheres and their use in electrochemical capacitive energy storage. AB - Nanostructured silicon hollow spheres with a thin shell have been synthesized by magnesium reduction of silica spheres, which possess a high BET surface area and are electrochemically active in capacitive energy storage with a maximum specific capacitance of 193 F g(-1) in the neutral Na(2)SO(4) aqueous solution. PMID- 22297485 TI - Socio-economic status, forms of capital and obesity. AB - INTRODUCTION: While the relationships among socio-economic status (SES) and obesity are powerful and synergistic, the SES construct is insufficient to describe some of the cultural influences on status production in society, and therefore on obesity production. Socio-economic status has two closely related dimensions. The economic one is represented by financial wealth while the social one can incorporate education, occupational prestige, authority and community standing. These are, however, incomplete explanations for the relationships between societal inequalities and obesity. DISCUSSION: Cultural factors associated with SES and obesity are examined here by using Bourdieu and Boltanski's theory of practice, which links economic, social and cultural forms of capital (or value) in an overarching category of symbolic capital. These represent categories through which power relationships within society are negotiated. This construct permits a more complete examination of societal stratification and its human biological consequences and amplifiers, since it incorporates the notion of cultural value in different groups of, for example, preferences in body size and shape. The focus is primarily on the USA, although it draws on literature from elsewhere in the industrialized world where appropriate. Differences in obesity rates across major ethnic groups are discussed, because this is an area in which forms of capital differ, and may offer new insights into obesity and factors that predispose to it, as forms of symbolic capital. PMID- 22297486 TI - Planimetrically determined vertical cup/disc and rim width/disc diameter ratios and related factors. AB - PURPOSE: To evaluate the distribution and factors related to planimetrically determined vertical cup/disc (v-C/D) and rim width/disc diameter (Rw/Dd) ratios of the optic discs in a population-based study of Japanese subjects without glaucoma. METHODS: Of 4632 eligible residents 40 years of age and older, 3762 residents underwent a detailed ocular examination including sequential optic disc stereo photography with a digital nonmydriatic fundus camera. The photographs were assessed by computer-assisted planimetry. The authors studied both eyes of 2311 nonglaucomatous subjects and only one right (left) eye of 196 (175) subjects for whom disc stereo photographs were of acceptable quality. RESULTS: The median (2.5th and/or 97.5th percentile) disc area, v-C/D, its asymmetry, and the superior- and inferior-minimal Rw/Dd ratios were 2.56 (1.68, 3.71) mm(2), 0.56 (0.70), 0.05 (0.14), 0.18 (0.10), and 0.21 (0.12), respectively. Multiple regression analysis showed that males had larger discs and superior Rw/Dd and smaller inferior Rw/Dd ratios. Increased age was correlated with increased v-C/D and decreased superior and inferior Rw/Dd ratios. Higher intraocular pressure (IOP) and thinner central corneal thickness (CCT) were correlated with higher v C/D and smaller inferior rim/disc ratios, and lower diastolic ocular perfusion pressure (OPP) with greater v-C/D and smaller superior Rw/Dd ratios. CONCLUSIONS: In nonglaucomatous eyes, increased v-C/D and decreased superior and inferior Rw/Dd ratios were significantly correlated not only with increased age and disc size but also with higher IOP, lower diastolic OPP, and thinner CCT, suggesting that these simple disc parameters also represent vulnerability to glaucoma insults in nonglaucomatous eyes. PMID- 22297487 TI - Changes in murine hyalocytes are valuable early indicators of ocular disease. AB - PURPOSE: The distribution, density, and phenotype of hyalocytes or vitreous macrophages in mouse eyes was examined during normal aging and in models of background diabetic retinopathy, retinal vascular proliferation, and exposure to TLR4 and TLR9 ligands. METHODS: The phenotype and density of hyalocytes were investigated in retinal and ciliary body wholemounts of normal wild-type (WT; C57BL/6) mice at 7, 17, and 120 weeks of age, Ins2(Akita) mice, transgenic Kimba mice (VEGF-induced retinal neovascularization), and WT mice 24 hours after single intraperitoneal injection with lipopolysaccharide (LPS) or 1 week after three identical doses administered 2 weeks apart. Another group of mice each received a single topical drop of 20 MUg CpG-oligodeoxynucleotides (CpG-ODN) to the abraded corneal surface and were euthanized 1 week later. RESULTS: The data revealed an approximately fivefold increase in the density of preretinal hyalocytes in 120 week-old mice. Some hyalocytes in older eyes contained phagocytosed melanin. Hyalocyte density was doubled in Ins2(Akita) mice after only 3 to 4 weeks of hyperglycemia. Kimba mice had an eightfold increase in the density of hyalocytes, and many displayed signs of activation. WT mice exposed to single or multiple systemic doses of LPS showed a twofold to threefold increase in hyalocytes. Topical CpG-ODN treatment led to a very marked (sevenfold) increase in preretinal hyalocyte density. CONCLUSIONS: The present study demonstrated that murine hyalocytes were responsive to aging, hyperglycemia, locally produced VEGF, and both systemic and ocular-derived TLR ligands. Thus hyalocytes or vitreous macrophages may be a valuable and previously unrecognized sensitive indicator of pathologic changes in the eye. PMID- 22297488 TI - Silencing of Fem1cR3 gene expression in the DBA/2J mouse precedes retinal ganglion cell death and is associated with histone deacetylase activity. AB - PURPOSE: Downregulation of normal gene expression in dying retinal ganglion cells has been documented in both acute and chronic models of optic nerve disease. The authors examined the mechanism and timing of this phenomenon in DBA/2J mice, using genetically modified substrains of this inbred line. METHODS: DBA/2J mice, doubly congenic for the Bax mutant allele and the ganglion cell reporter gene Fem1c(Rosa3) (R3), were evaluated to elucidate the timing of loss of normal gene expression during the apoptotic process. The localization of histone deacetylase 3 (HDAC3) and nuclear histone H4 acetylation were examined by immunofluorescence in dying cells. The role of HDACs in gene silencing during glaucoma was interrogated using the global HDAC inhibitor trichostatin A (TSA). RESULTS: Silencing of the R3 allele occurred in Bax(-/-) ganglion cells, indicating that this process preceded the committed step of the intrinsic apoptotic pathway. Weekly TSA treatment, between the ages of 6 and 10 months, was able to attenuate the loss of R3 expression in the retina, but had no effect on optic nerve degeneration. Dying cells in aging DBA/2J mice exhibited nuclear localization of HDAC3 and a decrease in the level of H4 acetylation. CONCLUSIONS: Retinal ganglion cells exhibit a loss of normal gene expression as an early (pre-BAX involvement) part of their apoptotic program during glaucomatous degeneration. This process can be ameliorated, but not completely blocked, using HDAC inhibitors. Epigenetic changes to active chromatin, such as deacetylation, may be mediated by HDAC3 in dying neurons. PMID- 22297489 TI - In vivo assessment of antimicrobial efficacy of silver-impregnated contact lens storage cases. AB - PURPOSE: To evaluate microbial contamination in silver-impregnated contact lens (CL) storage cases while establishing the effect of "wet " and "dry " case maintenance and to determine its association with clinical signs, symptoms, and compliance. METHODS: Two noncontemporaneous prospective studies were conducted. Regular storage cases in study 1 (n = 40) and silver-impregnated cases in study 2 (n = 41) were used in conjunction with CL solution and CLs (balafilcon A). Cases were replaced monthly and collected at 1, 3, and 4 (for silver-impregnated cases only) months. Regular cases and the fourth-month silver-impregnated cases were maintained dry, and the other cases were maintained wet between uses. At collection, storage cases were sampled and cultured for microbial identification and enumeration. Ocular clinical findings, subjective responses to CL wear, and compliance were recorded at each visit. RESULTS: The percentages of microbial contamination for silver-impregnated and regular cases were 71% and 82% respectively. There were significantly (P < 0.005) fewer organisms in silver impregnated cases (1.7 log CFU per well) than in regular cases (4.1 log CFU per well). In particular, silver-impregnated cases showed lower levels of Gram negative bacteria (P = 0.04), Gram-positive bacilli (P = 0.03), and fungi (P = 0.006). Maintaining the silver-impregnated cases wet resulted in a lower percentage of contamination (71%; P < 0.01) than maintaining them dry (94%). There was no association between any clinical signs, symptoms, or compliance and microbial contamination of storage cases. CONCLUSIONS: More than 70% of the storage cases used in daily wear CL care for a month was contaminated irrespective of the types of cases. However, silver-impregnated cases were colonized by reduced levels of Gram-negative bacteria. PMID- 22297490 TI - Differentiation between infectious and noninfectious ulcerative keratitis by Raman spectra of human teardrops: a pilot study. AB - PURPOSE: The aim of this study was to use Raman spectra of tears to differentiate between infectious and noninfectious ulcerative keratitis. METHODS: Raman microspectroscopy was applied using the drop-coating deposition method on Ti/Au coated glass slides to obtain sample spectra from different human tear groups, including tears from healthy subjects and from patients with infectious and noninfectious ulcerative keratitis. By comparing the difference spectra of the groups, the authors identified local Raman features useful for differentiation of ulcerative keratitis. Principal components (PCs) of normal tears were used as affined spectral coordinates. After performing projections of Raman spectra of both infectious and noninfectious tear samples, the authors compared the two groups to identify global spectral parameters with differential statistical significance. RESULTS: Differentiation between infectious and noninfectious ulcerative keratitis might be made directly through observation of the normalized tear Raman spectra or the transformed principal scores. Spectral segments with differential statistical significance included 878~888 cm(-1), 885~888 cm(-1), 945~993 cm(-1), 1007~1015 cm(-1), 1074~1100 cm(-1), 1090~1094 cm(-1), 1096~1099 cm(-1), 1386~1403 cm(-1), 1463~1469 cm(-1), 1469~1473 cm(-1), 1557~1563 cm(-1), 1584~1588 cm(-1), and 1614~1621 cm(-1). There were two PCs with statistically significant differences for the two groups of ulcerative keratitis, PC1 (P = 0.01) and PC2 (P = 0.05). CONCLUSIONS: This novel approach using the analysis of Raman spectra of teardrop samples for differentiation of ulcerative keratitis demonstrates the potential application of Raman microspectroscopy for clinical practice. This technology should complement the conventional cytological method for rapid diagnosis in the clinician's office. PMID- 22297491 TI - Automated assessment of drusen using three-dimensional spectral-domain optical coherence tomography. AB - PURPOSE: To compare automated assessment of macular drusen delineated by the authors' originally developed algorithm on three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) with the assessment by certified graders on color fundus photographs in nonneovascular age-related macular degeneration (AMD). METHODS: Automated assessment of macular drusen was performed using raster scan by 3D OCT scans in 18 eyes with nonneovascular AMD with at least one large druse (>=125 MUm) and predominantly soft indistinct drusen. Drusen was defined as the regions that have the distance between the retinal pigment epithelium and calculated Bruch's membrane lines > predefined threshold distances. The agreement was assessed on maximum drusen size and drusen area within grid between 3D SD-OCT and color fundus photographs, and false-negative and false-positive drusen at each threshold distance. RESULTS: There was agreement or agreement within one step in all eyes in maximum drusen size, and 15 (83.3%) of the eyes in the drusen area, except 6 pixels, regardless of threshold distances. However, the number of eyes with exact agreement in the drusen area increased when the threshold distances were smaller than 4 pixels. In the three cases with disagreement in the drusen area, false-negative drusen on 3D SD-OCT were characterized by being small in area and height. CONCLUSIONS: Automated assessment of drusen parameters based on the authors' algorithm on 3D SD-OCT, which was limited by the poor detection ability of small drusen, showed good agreement with the assessment by certified graders on color fundus photography in these subjects. PMID- 22297492 TI - Suppression of type I collagen expression by miR-29b via PI3K, Akt, and Sp1 pathway in human Tenon's fibroblasts. AB - PURPOSE: To evaluate the expression profile of microRNAs (miRNAs) and their roles in human Tenon's fibroblasts (HTFs), and to establish an miRNA-based gene silencing method for antifibrosis in vitro. METHODS: The miRNA expression profile was analyzed by microarray using quiescent and transforming growth factor beta 1 (TGFbeta1)-stimulated primary HTFs, respectively. Candidate miRNAs were identified by quantitative RT-PCR. miRNAs potentially targeting fibrosis-related genes were predicted using a published algorithm. Predicted fibrosis-related genes regulated by candidate miRNAs were confirmed by transfection of the miRNA into HTF culture (with or without TGFbeta1 treatment), followed by quantitative RT-PCR and Western blot analysis. RESULTS: In all, 38 miRNAs were identified to be upregulated and 31 downregulated, in TGFbeta1-stimulated HTFs. Among those, the miR-29b, downregulated in TGFbeta1-treated HTFs, targeted a cadre of mRNAs that encode proteins involved in fibrosis, including PI3Kp85alpha, Sp1, and collagen type I alpha1 (Col1A1). Treatment of HTFs with TGFbeta1 activated the PI3K/Akt/Sp1 pathway and, consequently, induced an increase in the expression of type I collagen. Overexpression of miR-29b inhibited the PI3K/Akt/Sp1 pathway, and attenuated the expression of Col1A1. CONCLUSIONS. miR-29b acted as a suppressor of type I collagen gene by repressing the PI3K/Akt/Sp1 pathway in HTFs. Overexpression of miR-29b protected subconjunctival tissues against collagen production and fibrosis. These findings provided a novel rationale for the development of miRNA-based strategies for attenuating scar formation after glaucoma filtering surgery. PMID- 22297493 TI - Corneal surface asphericity, roughness, and transverse contraction after uniform scanning excimer laser ablation. AB - PURPOSE: To examine the interaction between the excimer laser and residual tissue. METHODS: Ten cadaveric porcine eyes with exposed corneal stroma and plastic test spheres underwent uniform 6-mm ablation with a scanning excimer laser. Corneal profilometry of the central 3 mm was measured with submicrometer resolution optical interferometry, before and after uniform excimer ablation. Eleven surface-marked eyes were photomicrographed before and after excimer ablation. Images were superimposed, and mark positional changes were measured. RESULTS: Uniform scanning excimer laser ablation of the corneal stroma produces a significant central steepening and peripheral flattening in the central 3-mm of the diameter. The central 1-mm corneal curvature radius (r) decreased from r = 10.07 +/- 0.44 (95% CI) to 7.22 +/- 0.30 mm, and the central 2-mm radius decreased from r = 10.16 +/- 0.44 to 8.10 +/- 0.43 mm. Q values, measuring asphericity in the 2-mm radius of the central cornea, were significantly lower before than after ablation (-5.03 +/- 4.01 vs. -52.4 +/- 18.7). Surface roughness increased significantly from 0.65 +/- 0.06 to 1.75 +/- 0.32 MUm after ablation. The central 2 mm of the stromal surface contracted by 2.21% +/- 0.80% at a sustained temperature of 5 degrees C. Ablation of plastic spheres produced no significant change. CONCLUSIONS: The excimer laser interacts with the nonablated residual stromal surface in a characteristic fashion not seen with isotropic, inorganic material. Increases in asphericity, surface roughness, surface contraction, and stromal morphologic changes are supportive of this interaction. The surface changes demonstrated may be indicative of temperature-induced transverse collagen fibril contraction and stress redistribution, or the ablation threshold of the stromal surface may be altered. This phenomenon may be of increased importance using lasers with increased thermal load. PMID- 22297494 TI - Effect of corneal stiffening on Goldmann applanation tonometry and Tono-Pen measurements in canine eyes. AB - PURPOSE: To experimentally examine the effect of increased corneal stiffness on Goldmann applanation tonometry (GAT) and Tono-Pen (Reichert, Inc., Depew, NY) measurements of intraocular pressure (IOP) in a canine eye model. METHODS: Twenty globes were recovered from 10 dogs with no known diseases. For each dog, corneal stiffening was induced in one eye with glutaraldehyde/phosphate buffered saline (PBS) immersion while the other cornea was immersed in PBS only. Acoustic impedance was measured before and after treatment in all eyes. After treatment, IOP was measured by GAT and Tono-Pen at true pressures of 10, 15, 20, 30, and 40 mm Hg. The corneas were then dissected for uniaxial tensile testing. The GAT/Tono Pen readings, corneal stiffness (measured by ultrasound and tensile tests), and corneal thickness were compared between the two groups. The correlations between GAT/Tono-Pen readings and corneal stiffness were evaluated. RESULTS: Acoustic impedance significantly increased after glutaraldehyde treatment (P < 0.01). Secant modulus at 1% strain was significantly higher in corneas treated with glutaradehyde/PBS than those treated with PBS only (P < 0.01). GAT and Tono-Pen readings were significantly higher at all pressure levels (P < 0.001) in the eyes with corneal stiffening. Both corneal acoustic impedance and secant modulus were significantly correlated with GAT/Tono-Pen readings at all pressure levels (P < 0.01). CONCLUSIONS: This study provided experimental evidence that corneal stiffening significantly increases GAT and Tono-Pen readings in canine eyes. Noninvasive ultrasound measurement of acoustic impedance may be used to evaluate corneal stiffness and improve the accuracy of clinical measurements of IOP. PMID- 22297495 TI - Nintendo Wii remote controllers for head posture measurement: accuracy, validity, and reliability of the infrared optical head tracker. AB - PURPOSE: To evaluate the accuracy, validity, and reliability of a newly developed infrared optical head tracker (IOHT) using Nintendo Wii remote controllers (WiiMote; Nintendo Co. Ltd., Kyoto, Japan) for measurement of the angle of head posture. METHODS: The IOHT consists of two infrared (IR) receivers (WiiMote) that are fixed to a mechanical frame and connected to a monitoring computer via a Bluetooth communication channel and an IR beacon that consists of four IR light emitting diodes (LEDs). With the use of the Cervical Range of Motion (CROM; Performance Attainment Associates, St. Paul, MN) as a reference, one- and three dimensional (1- and 3-D) head postures of 20 normal adult subjects (20-37 years of age; 9 women and 11 men) were recorded with the IOHT. RESULTS: In comparison with the data from the CROM, the IOHT-derived results showed high consistency. The measurements of 1- and 3-D positions of the human head with the IOHT were very close to those of the CROM. The correlation coefficients of 1- and 3-D positions between the IOHT and the CROM were more than 0.99 and 0.96 (P < 0.05, Pearson's correlation test), respectively. Reliability tests of the IOHT for the normal adult subjects for 1- and 3-D positions of the human head had 95% limits of agreement angles of approximately +/-4.5 degrees and +/-8.0 degrees , respectively. CONCLUSIONS: The IOHT showed strong concordance with the CROM and relatively good test-retest reliability, thus proving its validity and reliability as a head-posture-measuring device. Considering its high performance, ease of use, and low cost, the IOHT has the potential to be widely used as a head posture-measuring device in clinical practice. PMID- 22297496 TI - TSG-6 controls transcription and activation of matrix metalloproteinase 1 in conjunctivochalasis. AB - PURPOSE: To investigate the role of anti-inflammatory TSG-6 in controlling MMP-1 and MMP-3, which have been shown to be upregulated in conjunctivochalasis (CCh). METHODS: Immunostaining of TSG-6 was compared between normal and CCh conjunctiva and Tenon's capsule. Second cultures of normal and CCh fibroblasts were transfected with or without TSG-6 siRNA and then with or without the addition of TNF-alpha or IL-1beta. Cell lysates and culture media were collected to assess apoptosis with the use of ELISA and the expression of TSG-6, MMP-1, and MMP-3 transcripts and proteins with the use of qRT-PCR and Western blot analysis, respectively. RESULTS: TSG-6 expression was constitutive in the in vivo normal conjunctival epithelium. Significantly more TSG-6-positive cells than normal specimens were noted in CCh subconjunctival tissue and Tenon's capsule. TSG-6 was constitutively expressed intracellularly by both resting normal and CCh fibroblasts but was secreted extracellularly only by resting CCh fibroblasts. Intracellular and extracellular TSG-6 proteins were markedly upregulated by TNF alpha or IL-1beta in normal and CCh fibroblasts. Active MMP-1 was found in CCh fibroblasts intracellularly and extracellularly, whereas only proMMP-1 was found intracellularly in normal fibroblasts. Knockdown by TSG-6 siRNA upregulated more MMP-1 than MMP-3 transcripts in normal and CCh fibroblasts. TSG-6 siRNA led to extracellular MMP-1 expression by normal fibroblasts such as CCh fibroblasts. This activation of MMP-1 was further enhanced by IL-1beta. Cell apoptosis was higher in CCh fibroblasts and further aggravated by TSG-6 siRNA knockdown. CONCLUSIONS: TSG-6 exerts an anti-inflammatory function by counteracting the transcription of MMP-1 and MMP-3 and the activation of MMP-1. Dysfunction of TSG 6 might play a role in the pathogenesis of CCh. PMID- 22297497 TI - Multipotent stem cells from trabecular meshwork become phagocytic TM cells. AB - PURPOSE: To isolate and characterize stem cells from human trabecular meshwork (TM) and to investigate the potential of these stem cells to differentiate into TM cells. METHODS: Human trabecular meshwork stem cells (TMSCs) were isolated as side population cells by fluorescence-activated cell sorting or isolated by clonal cultures. Passaged TMSCs were compared with primary TM cells by immunostaining and quantitative RT-PCR. TMSC purity was assessed by flow cytometry and TMSC multipotency was examined by induction of neural cells, adipocytes, keratocytes, or TM cells. Differential gene expression was detected by quantitative RT-PCR, immunostaining, and immunoblotting. TM cell function was evaluated by phagocytic assay using inactivated Staphylococcus aureus bioparticles. RESULTS: Side population and clonal isolated cells expressed stem cell markers ABCG2, Notch1, OCT-3/4, AnkG, and MUC1 but not TM markers AQP1, MGP, CHI3L1, or TIMP3. Passaged TMSCs are a homogeneous population with >95% cells positive to CD73, CD90, CD166, or Bmi1. TMSCs exhibited multipotent ability of differentiation into a variety of cell types with expression of neural markers neurofilament, beta-tubulin III, GFAP; or keratocyte-specific markers keratan sulfate and keratocan; or adipocyte markers ap2 and leptin. TMSC readily differentiated into TM cells with phagocytic function and expression of TM markers AQP1, CHI3L1, and TIMP3. CONCLUSIONS: TMSCs, isolated as side population or as clones, express specific stem cell markers, are homogeneous and multipotent, with the ability to differentiate into phagocytic TM cells. These cells offer a potential for development of a novel stem cell-based therapy for glaucoma. PMID- 22297498 TI - Normalization of visual evoked potentials using underlying electroencephalogram levels improves amplitude reproducibility in rats. AB - PURPOSE: The visual evoked potential (VEP) is a frequently used noninvasive measurement of visual function. However, high-amplitude variability has limited its potential for evaluating axonal damage in both laboratory and clinical research. This study was conducted to improve the reliability of VEP amplitude measurement in rats by using electroencephalogram (EEG)-based signal correction. METHODS: VEPs of Sprague-Dawley rats were recorded on three separate days within 2 weeks. The original VEP traces were normalized by EEG power spectrum, which was evaluated by Fourier transform. A comparison of intersession reproducibility and intersubject variability was made between the original and corrected signals. RESULTS: Corrected VEPs showed lower amplitude intersession within-subject SD (Sw), coefficient of variation (CoV), and repeatability (R(95)) than the original signals (P < 0.001). The intraclass correlation coefficient (ICC) of the corrected traces (0.90) was also better than the original potentials (0.82). For intersubject variability, the EEG-based normalization improved the CoV from 44.64% to 30.26%. A linear correlation was observed between the EEG level and the VEP amplitude (r = 0.71, P < 0.0001). CONCLUSIONS: Underlying EEG signals should be considered in measuring the VEP amplitude. In this study, a useful technique was developed for VEP data processing that could also be used for other cortical evoked potential recordings and for clinical VEP interpretation in humans. PMID- 22297499 TI - Recovery of axonal transport after partial optic nerve damage is associated with secondary retinal ganglion cell death in vivo. AB - PURPOSE: Traumatic injury of the optic nerve leads to retrograde cell death of retinal ganglion cells (RGCs) but usually a certain percentage of neurons survive. It has been suggested that recovery of axonal transport is beneficial for survival. The present study was therefore performed to provide a synopsis of the temporal pattern of axonal transport decline/recovery and the viability of RGCs after optic nerve crush (ONC). METHODS: Fluorescent dyes were injected into the superior colliculus to retrogradely label RGCs. Axonal transport kinetics into the RGCs was visualized with in vivo confocal neuroimaging (ICON) in uninjured rats and in rats which had mild or moderate ONC. Red fluorescent beads were injected on day 2 post-ONC and green beads on day 7. RESULTS: At 2 to 4 days post-ONC significant axonal transport was detected, but within 1 week the transport of the fluorescent beads was decreased. Interestingly, during post-ONC week 3 the axon transport slowly recovered. However, despite this recovery, retrograde cell death rate continued and was even increased in a "second wave" of cell death in those neurons that displayed axon transport recovery. CONCLUSIONS: After damage many surviving RGCs lose their axon transport, but after approximately 3 weeks, this transport recovers again, a sign of intrinsic axon repair. Contrary to the prediction, axon transport recovery is not associated with better cell survival but rather with a second wave of cell death. Thus, the accelerated cell death associated with recovery of axon transport suggests the existence of a late retrograde cell death signal. PMID- 22297500 TI - Review of screening guidelines for non-AIDS-defining malignancies: evolving issues in the era of highly active antiretroviral therapy. AB - HIV-associated morbidity and mortality have declined dramatically in the era of HAART. Through direct and indirect benefits of HAART, people with HIV/AIDS are living longer, developing less AIDS-defining cancers and more cancers commonly seen in the seronegative population. Herein, we review cancer screening strategies for people living with HIV and compare and contrast them with those of the general population. The most noticeable differences occur in anal and cervical cancer screening. Although anal cancer is uncommon in the general population, it is more prevalent in men who have sex with men and people at high risk for human papillomavirus infection, especially those infected with HIV. To address this, we recommend that a digital rectal exam and a visual inspection be performed annually. In addition, an anal Pap test should be performed soon after the diagnosis of HIV infection, with follow-up testing every six months until two normal tests. Abnormal cytological results are then investigated with high resolution anoscopy and biopsy of suspicious lesions. In screening for cervical cancer, a Pap test should be performed during the anogenital exam after initial HIV diagnosis, with a second Pap six months later, then annually if the results are normal. A colposcopy should follow an abnormal result. Human papillomavirus testing as a screening method for cervical cancer in women with HIV can also be efficacious. In lung cancer screening, preliminary data suggest that low-dose computerized tomography may play an important role, but further research is needed. Screening for breast and colon cancer should follow guidelines for the general population. Early screening for prostate cancer based on a diagnosis of HIV lacks clear benefit. PMID- 22297501 TI - Temporal changes in the epidemiology of transmission of drug-resistant HIV-1 across the world. AB - A substantial number of studies have been performed across the world to determine transmitted drug resistance. Large variations between different parts of the world can be expected because of differences in availability over time of treatment. Time trend analyses are often not possible because of small numbers of included patients. In this review, we present the available data on the transmission of drug-resistant HIV, with a major emphasis on the time trends of drug resistance prevalences. We identified relevant literature by searching in PubMed through September 2009. Studies were grouped, according to the year of data collection, into the following time periods: < 2001, 2001-2003, > 2003. We selected a total of 215 studies, which included 43,170 patients. The following prevalences of transmission of drug-resistant HIV were found, in rank order: North America (12.9%), Europe (10.9%), Latin America (6.3%), Africa (4.7%), and Asia (4.2%). Changes over time in particular drugs classes were found in all parts of the world. Nucleoside reverse transcriptase inhibitor resistance declined over time in North America (p = 0.03), Europe (p < 0.001), and Latin America (p < 0.001). The decline in nucleoside reverse transcriptase inhibitor resistance reflects the improvement of treatment regimens in resource-rich settings. In contrast the resistance prevalence increased in Asia (p = 0.047) and Africa (p < 0.001). This can be explained by the antiretrovirals becoming more available during recent years in these continents. Nonnucleoside reverse transcriptase inhibitor resistance rose over time in North America (p < 0.001), Europe (p < 0.001), Latin America (p < 0.001), and Asia (p = 0.01). This paper gives a complete overview of the epidemiology of resistance of antiretroviral drugs in drug-naive patients worldwide. The time trends that were observed seem to reflect changes in describing prescriptions over time. Changes include the more wide-spread use of antiretroviral drugs in developing countries and the development of therapies from low-active mono-therapies to highly active antiretroviral regimens in the industrialized countries. PMID- 22297502 TI - HIV-1 molecular epidemiology in the Balkans: a melting pot for high genetic diversity. AB - The Balkans is a gateway between Europe, Asia, and the African continent, a fact with potential important consequences on the epidemiology of HIV-1 infection in the region. The duration of the HIV-1 epidemics in many countries of the Balkans is similar to the one in the Western European countries. However, striking differences exist in several countries of the region in both the epidemic situation and, even more so, in our knowledge about it. In particular, the molecular epidemiology of HIV in the Balkans is largely unknown. In order to gain some preliminary insight into HIV-1 diversity in the region, we reviewed the available molecular epidemiology data about HIV-1 diversity in 10 countries of the region: Albania, Bulgaria, Croatia, Greece, Montenegro, Romania, Slovenia, Serbia, Turkey, and Hungary, a neighboring country to four Balkan countries. The data were obtained either from published studies or in direct communication with the participating members. The existing molecular epidemiology data revealed a broad diversity in subtype distribution among Balkan countries. In several countries, subtype B is predominant (e.g. Serbia, Slovenia, and Hungary), while in others the proportion of non-B subtypes is much larger (Albania subtype A, Romania subtype F). In some areas, HIV-1 subtype distribution is marked by divergence between different risk groups or transmission routes (e.g. Croatia). Recently, HIV-1/AIDS epidemics in Eastern Europe have been among the fastest growing in the world. Many major contributing factors for the breakout and spread of these epidemics are present in many of the Balkan countries, as reflected through the process of social transition, wars, unemployment, extensive drug use, high sexual risk behavior, as well as other factors. Yet, in the Balkan countries the prevalence rate of HIV-1 infection is low, under 0.1 percent. Concomitantly, the molecular epidemiology of HIV-1 in the Balkans has not been thoroughly studied so far. The review and analysis of the available data indicate a broad diversity of circulating HIV-1 subtypes in the region, with the predominance of non-B clades in some countries, underscoring the need for an ongoing surveillance of HIV-1 diversity. The setup of a collaborative network might provide important information for the better management and control of the HIV-1 epidemic in the area. PMID- 22297503 TI - Renal complications in HIV disease: between present and future. AB - The recent introduction of new antiretroviral drugs, characterized by high efficiency and improved safety profiles, has not reduced the incidence of long term adverse effects, in some cases manifested as selective organ damage. The presence of organ damage in patients receiving antiretroviral treatment is not only the expression of treatment toxicity, but also a complex interaction between individual risk factors, HIV-correlated effects, and antiretroviral drug toxicity. Kidney damage belongs to these adverse events. Renal function abnormalities are present in a large percentage of patients with HIV infection. Moreover, HIV-associated renal disease seems to be associated with progression to AIDS and death. In this review we address the various aspects of the epidemiology of renal damage, the interaction and the convergent effect of HIV and antiretroviral drugs in the onset of kidney injury, the interplay between kidney function and other organ systems, early clinical management, the monitoring of renal function, and a proposal of clinical approach to kidney disease in daily practice. Finally, we discuss future perspectives of renal damage in HIV patients and evaluate the patient's perspective. PMID- 22297504 TI - Antiretroviral drugs for pre-exposure prophylaxis of HIV infection. AB - Though a large number of antiretrovirals have been developed for the treatment of HIV infection, new HIV infections continue to occur, especially among certain high-risk groups, such as men who have sex with men. Overall, the current estimated incidence of HIV infection is 2.5-fold higher than the number of individuals that begin antiretroviral therapy every year worldwide. Along with the personal drama caused by the diagnosis of HIV infection, other considerations in society, including economics and interpersonal relationships, make the need for HIV prevention strategies a priority. Though vaccines have shown great efficacy in the combat of other epidemics, currently there is no effective vaccine against HIV, and it is unlikely that any will become available in the near future. Thus, new approaches such as pre-exposure prophylaxis are viewed with increasing interest. The results from recent clinical trials have provided support in favor of distinct pre-exposure prophylaxis modalities. However, concerns exist about increasing risky behaviors and selection and spread of antiretroviral drug resistance with a broader use of pre-exposure prophylaxis. The aim of this review is to examine the evidence available on the effectiveness of pre-exposure prophylaxis and its potential influence on the HIV epidemics. PMID- 22297505 TI - State of the art in intravaginal ring technology for topical prophylaxis of HIV infection. AB - There is renewed interest in the development of long-term, controlled-release dosage forms for the intravaginal delivery of antiretrovirals for HIV prophylaxis. This interest has catalyzed a renaissance in vaginal drug delivery, increasing the fundamental understanding of determinants of controlled drug delivery in the vagina as well as development of new materials, delivery platforms, and animal models. Our goal in writing this review from the perspective of engineers and pharmaceutical scientists interested in prevention of sexually transmitted infections is to highlight the current state of the art, progress in preclinical programs, new drug-delivery device designs, and to discuss some of the important unknowns in this area of HIV prevention for the general audience involved in HIV research. As far as antiretrovirals are concerned, this review is limited to programs working with antiretrovirals that are supported with an investigational new drug filing. We draw primarily from published papers in the PubMed and CAS databases, however, many of the most recent advances have yet to appear in the peer-reviewed literature and for this class of publications we draw from a recent formulation workshop held by CONRAD as well as from the Microbicides, Controlled Release Society, and CROI meetings. PMID- 22297506 TI - Cirrhosis and pre-neoplastic lesions. PMID- 22297507 TI - Viruses: sophisticated biological machines. AB - Virus infection involves coordination of a series of molecular machines, including entry machines, replication machines, assembly machines, and genome packaging machines, leading to the production of infectious virions. This chapter provides an introduction to various viral molecular machines described in this book. PMID- 22297508 TI - F(1)-ATPase: a prototypical rotary molecular motor. AB - F(1)-ATPase, the soluble portion of ATP synthase, has been shown to be a rotary molecular motor in which the central gamma subunit rotates inside the cylinder made of alpha(3)beta(3) subunits. The rotation is powered by ATP hydrolysis in three catalytic sites, and reverse rotation of the gamma subunit by an external force leads to ATP synthesis in the catalytic sites. Here I look back how our lab became involved in the study of this marvelous rotary machine, and discuss some aspects of its rotary mechanism while confessing we are far from understanding. This article is a very personal essay, not a scientific review, for this otherwise viral machines book. PMID- 22297509 TI - Principles of virus structural organization. AB - Viruses, the molecular nanomachines infecting hosts ranging from prokaryotes to eukaryotes, come in different sizes, shapes, and symmetries. Questions such as what principles govern their structural organization, what factors guide their assembly, how these viruses integrate multifarious functions into one unique structure have enamored researchers for years. In the last five decades, following Caspar and Klug's elegant conceptualization of how viruses are constructed, high-resolution structural studies using X-ray crystallography and more recently cryo-EM techniques have provided a wealth of information on structures of a variety of viruses. These studies have significantly -furthered our understanding of the principles that underlie structural organization in viruses. Such an understanding has practical impact in providing a rational basis for the design and development of antiviral strategies. In this chapter, we review principles underlying capsid formation in a variety of viruses, emphasizing the recent developments along with some historical perspective. PMID- 22297511 TI - Contractile tail machines of bacteriophages. AB - Bacteriophages with contractile tails epitomize the concepts of "virus" and "phage" for many because the tails of these phages undergo a large conformational change - resembling the action of a syringe - upon the attachment to the host cell. The contractile tails belong to the recently recognized class of "contractile systems," which includes phage tails, their close relatives R-type pyocins, the bacterial type VI secretion system, and the virulence cassette of Photorhabdus. Their function is to deliver large proteins and/or DNA into the cytoplasm of a bacterial or eukaryotic cell. The structure of the core components of all contractile tail-like systems is conserved, but the corresponding genes have diverged to such a degree that the common ancestry can no longer be easily detected at the level of amino acid sequence. At present, it is unclear, whether the contractile systems originated in bacteria or in phages. This chapter describes the structure and function of phage contractile tails and compares them with other phage tails and with other known contractile systems. PMID- 22297510 TI - Reconstructing virus structures from nanometer to near-atomic resolutions with cryo-electron microscopy and tomography. AB - The past few decades have seen tremendous advances in single-particle electron cryo-microscopy (cryo-EM). The field has matured to the point that near-atomic resolution density maps can be generated for icosahedral viruses without the need for crystallization. In parallel, substantial progress has been made in determining the structures of nonicosahedrally arranged proteins in viruses by employing either single-particle cryo-EM or cryo-electron tomography (cryo-ET). Implicit in this course have been the availability of a new generation of electron cryo-microscopes and the development of the computational tools that are essential for generating these maps and models. This methodology has enabled structural biologists to analyze structures in increasing detail for virus particles that are in different morphogenetic states. Furthermore, electron imaging of frozen, hydrated cells, in the process of being infected by viruses, has also opened up a new avenue for studying virus structures "in situ". Here we present the common techniques used to acquire and process cryo-EM and cryo-ET data and discuss their implications for structural virology both now and in the future. PMID- 22297512 TI - Long noncontractile tail machines of bacteriophages. AB - In this chapter, we describe the structure, assembly, function, and evolution of the long, noncontractile tail of the siphophages, which comprise ~60% of the phages on earth. We place -particular emphasis on features that are conserved among all siphophages, and trace evolutionary connections between these phages and myophages, which possess long contractile tails. The large number of high resolution structures of tail proteins solved recently coupled to studies of tail related complexes by electron microscopy have provided many new insights in this area. In addition, the availability of thousands of phage and prophage genome sequences has allowed the delineation of several large families of tail proteins that were previously unrecognized. We also summarize current knowledge pertaining to the mechanisms by which siphophage tails recognize the bacterial cell surface and mediate DNA injection through the cell envelope. We show that phages infecting Gram-positive and Gram-negative bacteria possess distinct families of proteins at their tail tips that are involved in this process. Finally, we speculate on the evolutionary advantages provided by long phage tails. PMID- 22297513 TI - Short noncontractile tail machines: adsorption and DNA delivery by podoviruses. AB - Tailed dsDNA bacteriophage virions bind to susceptible cells with the tips of their tails and then deliver their DNA through the tail into the cells to initiate infection. This chapter discusses what is known about this process in the short-tailed phages (Podoviridae). Their short tails require that many of these virions adsorb to the outer layers of the cell and work their way down to the outer membrane surface before releasing their DNA. Interestingly, the receptor-binding protein of many short-tailed phages (and some with long tails) has an enzymatic activity that cleaves their polysaccharide receptors. Reversible adsorption and irreversible adsorption to primary and secondary receptors are discussed, including how sequence divergence in tail fiber and tailspike proteins leads to different host specificities. Upon reaching the outer membrane of Gram negative cells, some podoviral tail machines release virion proteins into the cell that help the DNA efficiently traverse the outer layers of the cell and/or prepare the cell cytoplasm for phage genome arrival. Podoviruses utilize several rather different variations on this theme. The virion DNA is then released into the cell; the energetics of this process is discussed. Phages like T7 and N4 deliver their DNA relatively slowly, using enzymes to pull the genome into the cell. At least in part this mechanism ensures that genes in late-entering DNA are not expressed at early times. On the other hand, phages like P22 probably deliver their DNA more rapidly so that it can be circularized before the cascade of gene expression begins. PMID- 22297514 TI - Infection of cells by alphaviruses. AB - It is widely accepted that alphaviruses enter cells by a process involving endocytosis and low-pH-mediated virus membrane-cell membrane fusion. This model and the data supporting it have received extensive and numerous reviews. The major points presented in support of this model are summarized briefly herein. It is the primary objective of this review to present an alternative mechanism describing the penetration of cells by alphaviruses which does not involve endocytosis or exposure to acid environment. The data supporting this model are summarized in detail. PMID- 22297515 TI - Influenza virus entry. AB - As all the enveloped viruses, the entry of influenza viruses includes a number of steps in host cell infection. This chapter summarizes the current knowledge of the entry pathway and the role of the fusion protein of influenza virus, hemagglutinin, in this process. Hemagglutinin (HA) is a trimeric glycoprotein that is present in multiple copies in the membrane envelope of influenza virus. HA contains a fusion peptide, a receptor binding site, a metastable structural motif, and the transmembrane domain. The first step of influenza virus entry is the recognition of the host cell receptor molecule, terminal alpha-sialic acid, by HA. This multivalent attachment by multiple copies of trimetric HA triggers endocytosis of influenza virus that is contained in the endosome. The endosome trapped virus traffics via a unidirectional pathway to near the nucleus. At this location, the interior pH of the endosome becomes acidic that induces a dramatic conformational change in HA to insert the fusion peptide into the host membrane, induce juxtaposition of the two membranes, and form a fusion pore that allows the release of the genome segments of influenza virus. HA plays a key role in the entire entry pathway. Inhibitors of virus entry are potentially effective antiviral drugs of influenza viruses. PMID- 22297516 TI - Molecular mechanisms of HIV entry. AB - Human immunodeficiency virus (HIV) entry is a complex and intricate process that facilitates delivery of the viral genome to the host cell. The only viral surface protein, Envelope (Env), is composed of a trimer of gp120 and gp41 heterodimers. It is essentially a fusion machine cloaked in a shroud of carbohydrate structures and variable loops of amino acids that enable it to evade the humoral immune response. For entry to occur gp120 sequentially engages the host protein CD4 and then one of two chemokine coreceptors, either CCR5 or CXCR4. CD4 binding facilitates exposure and formation of the coreceptor-binding site, and coreceptor binding then triggers the membrane fusion machinery in the gp41 subunit. Our understanding of HIV entry has led to the development of successful small molecule inhibitors for the clinical treatment of HIV infection as well as insights into viral tropism and pathogenesis. PMID- 22297517 TI - Bunyavirus: structure and replication. AB - The Bunyaviridae family is comprised of a large number of negative-sense, single stranded RNA viruses that infect animals, insects, and plants. The tripartite genome of bunyaviruses, encapsidated in the form of individual ribonucleoprotein complexes, encodes four structural proteins, the glycoproteins Gc and Gn, the nucleoprotein N, and the viral polymerase L. Some bunyaviruses also use an ambi sense strategy to encode the nonstructural proteins NSs and NSm. While some bunyaviruses have a T = 12 icosahedral symmetry, others only have locally ordered capsids, or capsids with no detectable symmetry. Bunyaviruses enter cells through clathrin-mediated endocytosis or phagocytosis. In endosome, viral glycoproteins facilitate membrane fusion at acidic pH, thus allowing bunyaviruses to uncoat and deliver their genomic RNA into host cytoplasm. Bunyaviruses replicate in cytoplasm where the viral polymerase L catalyzes both transcription and replication of the viral genome. While transcription requires a cap primer for initiation and ends at specific termination signals before the 3' end of the template is reached, replication copies the entire template and does not depend on any primer for initiation. This review will discuss some of the most interesting aspects of bunyavirus replication, including L protein/N protein mediated cap snatching, prime-and-realign for transcription and replication initiation, translation-coupled transcription, sequence/secondary structure dependent transcription termination, ribonucleoprotein encapsidation, and N protein-mediated initiation of viral protein translation. Recent developments on the structure and functional characterization of the bunyavirus capsid and the RNA synthesis machineries (including both protein L and N) will also be discussed. PMID- 22297519 TI - Chaperonin-mediated folding of viral proteins. AB - Chaperonins are universally conserved molecular machines that facilitate the proper -folding of nascent and partially folded polypeptides into their respective three-dimensional structures. These multimeric protein complexes utilize the energy derived from ATP hydrolysis to fuel a protein-folding mechanism that consists of multiple rounds of substrate binding, encapsulation, and eventual expulsion back into the cytosolic environment. In this portion of the chapter, the structure and function of group I and group II chaperonins are discussed. Furthermore, the general mechanism of chaperonin-mediated protein folding is addressed in addition to illustrating how viral phages such as Lambda, T4, and RB49 exploit the host machinery for the proper folding of viral gene products. Lastly, the phiEL chaperonin from phage EL is revealed to be the first virally encoded chaperonin and is proposed to function independently of the host chaperonin machinery. The molecular architecture of the phiEL chaperonin, coupled with its unique functional abilities, renders its characterization a challenge and further highlights its novelty as a potentially whole new class of chaperonins. PMID- 22297518 TI - Viral polymerases. AB - Viral polymerases play a central role in viral genome replication and transcription. Based on the genome type and the specific needs of particular virus, RNA-dependent RNA polymerase, RNA-dependent DNA polymerase, DNA-dependent RNA polymerase, and DNA-dependent RNA polymerases are found in various viruses. Viral polymerases are generally active as a single protein capable of carrying out multiple functions related to viral genome synthesis. Specifically, viral polymerases use variety of mechanisms to recognize initial binding sites, ensure processive elongation, terminate replication at the end of the genome, and also coordinate the chemical steps of nucleic acid synthesis with other enzymatic activities. This review focuses on different viral genome replication and transcription strategies, and the polymerase interactions with various viral proteins that are necessary to complete genome synthesis. PMID- 22297520 TI - Building the machines: scaffolding protein functions during bacteriophage morphogenesis. AB - For a machine to function, it must first be assembled. The morphogenesis of the simplest icosahedral virus would require only 60 copies of a single capsid protein to coalesce. If the capsid protein's structure could be entirely dedicated to this endeavor, the morphogenetic mechanism would be relatively uncomplicated. However, capsid proteins have had to evolve other functions, such as receptor recognition, immune system evasion, and the incorporation of other structure proteins, which can detract from efficient assembly. Moreover, evolution has mandated that viruses obtain additional proteins that allow them to adapt to their hosts or to more effectively compete in their respective niches. Consequently, genomes have increased in size, which has required capsids to do likewise. This, in turn, has lead to more complex icosahedral geometries. These challenges have driven the evolution of scaffolding proteins, which mediate, catalyze, and promote proper virus assembly. The mechanisms by which these proteins perform their functions are discussed in this review. PMID- 22297521 TI - Bacteriophage HK97 capsid assembly and maturation. AB - The Escherichia coli phage HK97 has provided a productive experimental system for investigating how virus capsids are assembled from their protein components and how the assembled capsids mature to their final form. Aspects of the process for which the HK97 system has been particularly informative include assembly of the icosahedral capsid shell from the component proteins, structure of the capsid subunits and of the entire capsid as it progresses through its maturation, and the mechanism of the covalent cross-linking that links the subunits together into viral chain mail. The structural dynamics of the maturation as well as the energetics that drives maturation forward are beginning to be understood. PMID- 22297522 TI - Lipid-containing viruses: bacteriophage PRD1 assembly. AB - PRD1 is a tailless icosahedrally symmetric virus containing an internal lipid membrane beneath the protein capsid. Its linear dsDNA genome and covalently attached terminal proteins are delivered into the cell where replication occurs via a protein-primed mechanism. Extensive studies have been carried out to decipher the roles of the 37 viral proteins in PRD1 assembly, their association in virus particles and lately, especially the functioning of the unique packaging machinery that translocates the genome into the procapsid. These issues will be addressed in this chapter especially in the context of the structure of PRD1. We will also discuss the major challenges still to be addressed in PRD1 assembly. PMID- 22297523 TI - Assembly of large icosahedral double-stranded RNA viruses. AB - Double-stranded RNA (dsRNA) viruses are a diverse group of viruses infecting hosts from bacteria to higher eukaryotes. Among the hosts are humans, domestic animals, and economically important plant species. Fine details of high resolution virion structures have revealed common structural characteristics unique to these viruses including an internal icosahedral capsid built from 60 asymmetric dimers (120 monomers!) of the major coat protein. Here we focus mainly on the structures and assembly principles of large icosahedral dsRNA viruses belonging to the families of Cystoviridae and Reoviridae. It is obvious that there are a variety of assembly pathways utilized by different viruses starting from similar building blocks and reaching in all cases a similar capsid architecture. This is true even with closely related viruses indicating that the assembly pathway per se is not an indicator of relatedness and is achieved with minor changes in the interacting components. PMID- 22297524 TI - The papillomavirus virion: a machine built to hide molecular Achilles' heels. AB - Papillomaviruses are a diverse group of DNA viruses that infect the skin and mucosal tissues of vertebrates. More than 100 distinct human papillomavirus (HPV) genotypes have so far been identified. A subset of HPVs is known to cause human cancer. Although recently developed vaccines protect vaccinated individuals from the two most carcinogenic HPV types, there is a pressing need for next-generation vaccines that might offer broad-spectrum protection against the full range of cancer-causing HPVs. The ongoing development of such vaccines will be facilitated by a deeper understanding of the mechanics of the assembly of the nonenveloped papillomavirus virion, as well as the machine-like structural changes that occur in the virion during the process of infectious entry into host cells. This chapter reviews the field's current knowledge of these two aspects of papillomavirus biology and speculates about areas where further work is needed. PMID- 22297525 TI - Procapsid assembly, maturation, nuclear exit: dynamic steps in the production of infectious herpesvirions. AB - Herpesviruses, a family of animal viruses with large (125-250 kbp) linear DNA genomes, are highly diversified in terms of host range; nevertheless, their virions conform to a common architecture. The genome is confined at high density within a thick-walled icosahedral capsid with the uncommon (among viruses, generally) but unvarying triangulation number T = 16. The envelope is a membrane in which some 11 different viral glycoproteins are implanted. Between the capsid and the envelope is a capacious compartment called the tegument that accommodates ~20-40 different viral proteins (depending on which virus) destined for delivery into a host cell. A strong body of evidence supports the hypothesis that herpesvirus capsids and those of tailed bacteriophages stem from a distant common ancestor, whereas their radically different infection apparatuses - envelope on one hand and tail on the other - reflect subsequent coevolution with divergent hosts. Here we review the molecular components of herpesvirus capsids and the mechanisms that regulate their assembly, with particular reference to the archetypal alphaherpesvirus, herpes simplex virus type 1; assess their duality with the capsids of tailed bacteriophages; and discuss the mechanism whereby, once DNA packaging has been completed, herpesvirus nucleocapsids exit from the nucleus to embark on later stages of the replication cycle. PMID- 22297526 TI - Assembly and architecture of HIV. AB - HIV forms spherical, membrane-enveloped, pleomorphic virions, 1,000-1,500 A in diameter, which contain two copies of its single-stranded, positive-sense RNA genome. Virus particles initially bud from host cells in a noninfectious or immature form, in which the genome is further encapsulated inside a spherical protein shell composed of around 2,500 copies of the virally encoded Gag polyprotein. The Gag molecules are radially arranged, adherent to the inner leaflet of the viral membrane, and closely associated as a hexagonal, paracrystalline lattice. Gag comprises three major structural domains called MA, CA, and NC. For immature virions to become infectious, they must undergo a maturation process that is initiated by proteolytic processing of Gag by the viral protease. The new Gag-derived proteins undergo dramatic rearrangements to form the mature virus. The mature MA protein forms a "matrix" layer and remains attached to the viral envelope, NC condenses with the genome, and approximately 1,500 copies of CA assemble into a new cone-shaped protein shell, called the mature capsid, which surrounds the genomic ribonucleoprotein complex. The HIV capsid conforms to the mathematical principles of a fullerene shell, in which the CA subunits form about 250 CA hexamers arrayed on a variably curved hexagonal lattice, which is closed by incorporation of exactly 12 pentamers, seven pentamers at the wide end and five at the narrow end of the cone. This chapter describes our current understanding of HIV's virion architecture and its dynamic transformations: the process of virion assembly as orchestrated by Gag, the architecture of the immature virion, the virus maturation process, and the structure of the mature capsid. PMID- 22297527 TI - Condensed genome structure. AB - Large, tailed dsDNA-containing bacteriophage genomes are packaged to a conserved and high density (~500 mg/ml), generally in ~2.5-nm, duplex-to-duplex, spaced, organized DNA shells within icosahedral capsids. Phages with these condensate properties, however, differ markedly in their inner capsid structures: (1) those with a naked condensed DNA, (2) those with many dispersed unstructured proteins embedded within the DNA, (3) those with a small number of localized proteins, and (4) those with a reduced or DNA-free internal protein structure of substantial volume. The DNA is translocated and condensed by a high-force ATPase motor into a procapsid already containing the proteins that are to be ejected together with the DNA into the infected host. The condensed genome structure of a single-phage type is unlikely to be precisely determined and can change without loss of function to fit an altered capsid size or internal structure. Although no such single-phage condensed genome structure is known exactly, it is known that a single general structure is unlikely to apply to all such phages. PMID- 22297528 TI - The bacteriophage DNA packaging machine. AB - Large dsDNA bacteriophages and herpesviruses encode a powerful ATP-driven DNA translocating machine that encapsidates a viral genome into a preformed capsid shell or prohead. The key components of the packaging machine are the packaging enzyme (terminase, motor) and the portal protein that forms the unique DNA entrance vertex of prohead. The terminase complex, comprised of a recognition subunit (small terminase) and an endonuclease/translocase subunit (large terminase), cuts viral genome concatemers. The terminase-viral DNA complex docks on the portal vertex, assembling a motor complex containing five large terminase subunits. The pentameric motor processively translocates DNA until the head shell is full with one viral genome. The motor cuts the DNA again and dissociates from the full head, allowing head-finishing proteins to assemble on the portal, sealing the portal, and constructing a platform for tail attachment. A body of evidence from molecular genetics and biochemical, structural, and biophysical approaches suggests that ATP hydrolysis-driven conformational changes in the packaging motor (large terminase) power DNA motion. Various parts of the motor subunit, such as the ATPase, arginine finger, transmission domain, hinge, and DNA groove, work in concert to translocate about 2 bp of DNA per ATP hydrolyzed. Powerful single-molecule approaches are providing precise delineation of steps during each translocation event in a motor that has a speed as high as a millisecond/step. The phage packaging machine has emerged as an excellent model for understanding the molecular machines, given the mechanistic parallels between terminases, helicases, and numerous motor proteins. PMID- 22297529 TI - The dsDNA packaging motor in bacteriophage o29. AB - The tailed dsDNA bacteriophage o29 packages its 19.3-kb genome into a pre assembled prolate icosahedral procapsid structure using a phage-encoded macromolecular motor. This process is remarkable considering that compaction of DNA to near crystalline densities within the confined space of the capsid requires that the motor work against considerable entropic, enthalpic, and DNA bending energies. The heart of the bacteriophage o29 packaging motor consists of three macromolecular components: the connector protein, an RNA molecule known as the pRNA, and an ATPase. The pRNA is thus far unique to o29, but the connector and ATPase are homologous to portal and terminase proteins, respectively, in other tailed dsDNA bacteriophages. Despite decades of effort and a wealth of genetic, biochemical, biophysical, structural, and single particle data, the mechanism of DNA packaging in bacteriophage o29 remains elusive. In this chapter, we describe the development of a highly efficient in vitro DNA packaging system for o29, review the data available for each individual macromolecular component in the packaging motor, and present and evaluate various packaging mechanisms that have been proposed to explain the available data. PMID- 22297531 TI - Genome gating in tailed bacteriophage capsids. AB - Tailed bacteriophages use a portal system for genome entry and exit from viral capsids. Here, we review the mechanisms how these movements are controlled by the genome gatekeeper that assembles at the portal structure. Phage DNA is packaged at high pressure inside the viral capsid by a powerful motor. The viral genome is translocated through the central channel of the portal protein found at a single vertex of the capsid. Packaging is normally terminated by endonucleolytic cleavage of the substrate DNA followed by disassembly of the packaging motor and closure of the portal system, preventing leakage of the viral genome. This can be achieved either by conformational changes in the portal protein or by sequential addition of proteins that extend the portal channel (adaptors) and physically close it preventing DNA exit (stoppers). The resulting connector structure provides the interface for assembly of short tails (podoviruses) or for attachment of preformed long tails (siphoviruses and myoviruses). The connector maintains the viral DNA correctly positioned for ejection that is triggered by interaction of the phage particle with bacterial receptors. Recent exciting advances are providing new molecular insights on the mechanisms that ensure precise coordination of these critical steps required both for stable viral genome packaging and for its efficient release to initiate infection. PMID- 22297532 TI - Packaging in dsRNA viruses. AB - Several families of viruses have segmented genomes with 3-12 chromosomes. They are capable of packaging these segments in a precise manner so that each virus particle contains one each of the genomic segments. The Cystoviridae are a family of bacteriophages that contain three genomic segments of dsRNA. During infection, the virus produces empty dodecahedral core particles that have the ability to specifically package plus strand transcripts of the genomic segments. The program of packaging makes use of the conformational changes in the surface of the particle as each transcript is packaged. The particles have complexes of a hexameric NTPase that serve as motors to bring the transcripts into the particle, and they have polymerase molecules in the interior that synthesize minus and plus strand copies of the genomic segments. PMID- 22297530 TI - Single-molecule studies of viral DNA packaging. AB - Many double-stranded DNA bacteriophages and viruses use specialized ATP-driven molecular machines to package their genomes into tightly confined procapsid shells. Over the last decade, single-molecule approaches - and in particular, optical tweezers - have made key contributions to our understanding of this remarkable process. In this chapter, we review these advances and the insights they have provided on the packaging mechanisms of three bacteriophages: phi 29, lambda, and T4. PMID- 22297533 TI - Mechanism of RNA packaging motor. AB - P4 proteins are hexameric RNA packaging ATPases of dsRNA bacteriophages of the Cystoviridae family. P4 hexamers are integral part of the inner polymerase core and play several essential roles in the virus replication cycle. P4 proteins are structurally related to the hexameric helicases and translocases of superfamily 4 (SF4) and other RecA-like ATPases. Recombinant P4 proteins retain their 5' to 3' helicase and translocase activity in vitro and thus serve as a model system for studying the mechanism of action of hexameric ring helicases and RNA translocation. This review summarizes the different roles that P4 proteins play during virus assembly, genome packaging, and transcription. Structural and mechanistic details of P4 action are laid out to and subsequently compared with those of the related hexameric helicases and other packaging motors. PMID- 22297534 TI - Helical viruses. AB - Virtually all studies of structure and assembly of viral filaments have been made on plant and bacterial viruses. Structures have been determined using fiber diffraction methods at high enough resolution to construct reliable molecular models or several of the rigid plant tobamoviruses (related to tobacco mosaic virus, TMV) and the filamentous bacteriophages including Pf1 and fd. Lower resolution structures have been determined for a number of flexible filamentous plant viruses using fiber diffraction and cryo-electron microscopy. Virions of filamentous viruses have numerous mechanical functions, including cell entry, viral disassembly, viral assembly, and cell exit. The plant viruses, which infect multicellular organisms, also use virions or virion-like assemblies for transport within the host. Plant viruses are generally self-assembling; filamentous bacteriophage assembly is combined with secretion from the host cell, using a complex molecular machine. Tobamoviruses and other plant viruses disassemble concomitantly with translation, by various mechanisms and involving various viral and host assemblies. Plant virus movement within the host also makes use of a variety of viral proteins and modified host assemblies. PMID- 22297535 TI - Evaluation of the Icare-ONE rebound tonometer as a self-measuring intraocular pressure device in normal subjects. AB - PURPOSE: To compare Icare ONE rebound self-tonometer (ICRBT) measurements with Goldman applanation tonometry (GAT). METHODS: A trained examiner instructed each of 60 normal subjects on use of the ICRBT. Each subject then took two measurements of his/her own pressure using the ICRBT. Finally, a different examiner, who was masked to the earlier readings, measured IOP by GAT. Bland Altman limits of agreement (LOA), intraclass correlation coefficients (ICCs), Kappa values, and paired t-test were used to assess the agreement between the two methods. Pearson's correlation coefficient was used for correlation analysis. RESULTS: All of the subjects were able to obtain correct measurements with ICRBT after three attempts. The mean intraocular pressure with ICRBT and GAT measurements were 16.0 +/- 3.3 mmHg and 13.7 +/- 2.5 mmHg respectively. The mean difference between patient's ICRBT and technician's GAT measurements was 2.3 mmHg (p < 0.001). In 63% (38/60) of the cases the IOP difference (ICRBT - GAT) was within +/- 3 mmHg. The weighted Kappa for the IOP measurements of the two methods was 0.49 (95% CI: 0.30-0.68, p < 0.001), indicating acceptable agreement. A significantly positive correlation was found between ICRBT IOP measurements and central corneal thickness (CCT) (r = 0.48, p < 0.001). In addition, the difference in IOP measurements (ICRBT - GAT) between the two methods was positively correlated with CCT (r = 0.31, p = 0.015), indicating that greater thickness is associated with greater differences between the two methods. CONCLUSION: The ICRBT was reliable in the hands of normal subjects, and may be used for self-monitoring of IOP. ICRBT measurements generally overestimated GAT measurements. PMID- 22297536 TI - Persistent bloody tears as the initial manifestation of conjunctival chloroma associated with chronic myelogenous leukemia. PMID- 22297537 TI - Long-term follow-up of invasive ocular surface squamous cell carcinoma treated with excision, cryotherapy, and topical mitomycin C. AB - BACKGROUND: To evaluate the efficacy of surgical excision, cryotherapy and topical Mitomycin C (MMC) for ocular surface squamous cell carcinoma (SCC) with at least 24 months follow-up. METHODS: Seventeen patients with primary and recurrent invasive SCC of ocular surface underwent surgical excision and map biopsy of the margins, and double freeze-thaw cryotherapy of the bed and margins. Topical MMC (0.04%, 4 times daily) was commenced 7-10 days after operation. It was delivered in cycles that consisted of medication 4 times daily for 7 consecutive days followed by 7 consecutive days of no medication. Patients with primary SCC received two cycles (protocol 1) and those with recurrent SCC received three cycles (protocol 2). Patients with intra-ocular and or orbital extension or those with less than 24 months of follow-up were excluded. The frequency of tumor recurrence and complications associated with treatment were measured. RESULTS: Mean age was 70.7 years (SD = 10, range: 48-80). Mean follow up time was 48 months (SD = 21, range: 24-89). There were 12 patients with primary SCC and five with recurrent SCC. Mean largest diameter was 9.7 mm (3-20). Surgical margins were free in 12 cases. One patient with recurrent SCC who received protocol 2 treatment developed recurrence 9 months after excision, and remained free of recurrence 24 months after second treatment. Complications comprised transient mild punctate corneal epithelial erosion (eight), irritation and conjunctival hyperemia (11), corneal scar (six), and scleral thinning (three). All except one responded well to conservative management. One scleral thinning required scleral patch graft 1 year after treatment. CONCLUSION: The combination of surgical excision, cryotherapy, and post-operative topical mitomycin-C was effective treatment for ocular surface invasive SCC in long-term follow-up. PMID- 22297539 TI - Johann Christian August Heinroth (1773-1843): the first professor of psychiatry as a psychotherapist. AB - Heinroth is known as the first professor of psychiatry. His chair was established 200 years ago on the 21st of October 1811. His major importance for the history of psychotherapy has not yet been acknowledged. Heinroth regarded restriction as well as activation as fundamental remedies for mental illnesses. Restriction meant making a voluntary decision to live a life based on religious faith and to abstain from earthly satisfaction. Within his specific psychotherapeutical module the ''direct-psychic''method-he utilized the patient's mental powers-mood, mind and will, but also his spirituality. His therapeutic approach additionally contained elements of cognitive,behavioral and conversational therapy. PMID- 22297538 TI - GM-CSF protects rat photoreceptors from death by activating the SRC-dependent signalling and elevating anti-apoptotic factors and neurotrophins. AB - BACKGROUND: The term retinitis pigmentosa (RP) comprises a heterogeneous group of hereditary and sporadic human retinal degenerative diseases. The molecular and cellular events still remain obscure, thus hiding effective therapies. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic factor which plays a crucial role in protecting neuronal cells. Binding of GM-CSF to its receptor induces several intracellular signaling pathways and kinases. Here we examined whether GM-CSF has a neuroprotective effect on photoreceptor degeneration in Royal College of Surgeons (RCS) rats. METHODS: GM-CSF was injected into the vitreous body of RCS rats either once at the onset of photoreceptor degeneration at day 21, or twice at day 21 and day 42. At day 84, when photoreceptor degeneration is completed, the rats were sacrificed, their eyes enucleated and processed for histological staining and counting the surviving photoreceptor nuclei. The expression of apoptosis-related factors, such as BAD, APAF1 and BCL-2 was examined by Western blot analysis. The expression of neurotrophins such as ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF), and glia-derived neurotrophic actor (GDNF), as well as glial fibrillary acidic protein (GFAP) was analysed by Western blots and immunohistochemistry. The expression of JAK/STAT, ERK1/2 and SRC pathway proteins was assessed by Western blot analysis. RESULTS: GM-CSF protects significantly against photoreceptor degeneration in comparison to control group. After a single injection of GM-CSF at P21, a 4-fold increase of photoreceptors was observed, whereas eyes which received a repeated injection of GM-CSF at P42 showed a 10 fold increase of photoreceptors. Western blot analysis revealed a decreased BAD and an increased pBAD and BCL-2 expression, indicating changed expression profiles of apoptosis-related proteins. Neurotrophic factors examined are up regulated, whereas GFAP was also modulated. At cell signalling levels, GM-CSF activates SRC-dependent STAT3 which is independent of JAK2, while proteins of the ERK1/2 pathway are not affected. CONCLUSIONS: The data suggest that GM-CSF is a potent therapeutic agent in photoreceptor degeneration caused by mutation of the receptor tyrosine kinase gene (Mertk), and may be also effective in other photoreceptor degeneration. PMID- 22297540 TI - Mobility and carrier density in p-type GaAs nanowires measured by transmission Raman spectroscopy. AB - The unambiguous measurement of carrier concentration and mobility in semiconductor nanowires remains a challenging task. This is a consequence of their one-dimensional nature and the incompatibility with Hall or van der Pauw measurements. We propose a method that allows the direct determination of mobility and carrier concentration in nanowires in a contact-less manner. We demonstrate how forward Raman scattering enables the measurement of phonon plasmon interactions. By applying this method to p-type GaAs nanowires, we were able to directly obtain values of the carrier concentration between 3.0 * 10(17) and 7.4 * 10(18) cm(-3) and a mobility of 31 cm(2) (V s)(-1) at room temperature. This study opens the path towards the study of plasmon-phonon interactions in semiconductor nanowires. PMID- 22297541 TI - Protective Effects of Adeno-associated Virus Mediated Brain-derived Neurotrophic Factor Expression on Retinal Ganglion Cells in Diabetic Rats. AB - Adeno-associated virus vector plasmid carrying the expression cassette of brain derived neurotrophic factor (BDNF), pAAV-BDNF, was constructed and packaged into recombinant adeno-associated virus (rAAV-BDNF). The rAAV-BDNF was intravitreally injected into streptzotocin (STZ)-induced diabetic Sprague-Dawley (SD) Rats. Data showed that over-expression of BDNF could increase alive retinal ganglion cell (RGC) number and improve its function in streptzotocin(STZ)-induced diabetic rats, which might be a new method to treat diabetic neuropathy and retinopathy. PMID- 22297542 TI - Stress, allostatic load, catecholamines, and other neurotransmitters in neurodegenerative diseases. AB - As populations age, the prevalence of geriatric neurodegenerative diseases will increase. These diseases generally are multifactorial, arising from complex interactions among genes, environment, concurrent morbidities,treatments, and time. This essay provides a concept for the pathogenesis of Lewy body diseases such as Parkinson disease, by considering them in the context of allostasis and allostatic load. Allostasis reflects active, adaptive processes that maintain apparent steady states, via multiple,interacting effectors regulated by homeostatic comparators-"homeostats". Stress can be defined as a condition or state in which a sensed discrepancy between afferent information and a setpoint for response leads to activation of effectors, reducing the discrepancy. "Allostatic load" refers to the consequences of sustained or repeated activation of mediators of allostasis. From the analogy of an idling car, the revolutions per minute of the engine can be maintained at any of a variety of levels (allostatic states).Just as allostatic load (cumulative wear and tear) reflects design and manufacturing variations, byproducts of combustion,and time, eventually leading to engine breakdown,allostatic load in catecholaminergic neurons might eventually lead to Lewy body diseases. Central to the argument is that catecholaminergic neurons leak vesicular contents into the cytoplasm continuously during life and that catecholaminesin the neuronal cytoplasm are autotoxic. These neurons therefore depend on vesicular sequestration to limit autotoxicity of cytosolic transmitter. Parkinson disease might be a disease of the elderly because of allostatic load, which depends on genetic predispositions,environmental exposures, repeated stress-related catecholamine release, and time. PMID- 22297543 TI - Hypoxia inducible factor-1: its potential role in cerebral ischemia. AB - A divergence in the supply and consumption of oxygen in brain tissue initiates complex cycle of biochemical and molecular events resulting in neuronal death. To overcome such adverse situation, the tissue has to adopt some cellular mechanisms such as induction of various transcription factors, such as hypoxia inducible factor (HIF). It is a transcriptional regulator of oxygen homeostasis and key factor to generate the adaptive responses through upregulation of various target genes involved in the erythropoiesis, angiogenesis as well as glucose metabolism and transport. On the other hand, some studies do suggest that HIF also plays a detrimental role in ischemic reperfusion injury by inducing the pro apoptotic molecules, cytokines such as Nix, BNip3, and IL-20 which cause mitochondrial dysfunction leading to cell death. Hence, modulation of HIF-1 activity seems to provide an innovative therapeutic target to reduce the cellular damage, which arises from ischemic injury. Apart from traditional oxygen dependent HIF regulation, the focus has now shifted toward oxygen independent regulation in cell specific manner through reactive oxygen species involving hypoxia-associated factor, and heat shock protein 90, etc. Therefore, future development of such small molecule regulators for HIF-1 stability and signaling may prove useful to therapeutically target for enhancing recovery and repair in I/R injury. PMID- 22297544 TI - Stress cardiomyopathy: a syndrome of catecholamine-mediated myocardial stunning? AB - During the past few years, a novel syndrome of heart failure and transient left ventricular systolic dysfunction precipitated by acute emotional or physical stress has been described. While patients with "stress cardiomyopathy"(SCM) typically present with signs and symptoms that resemble an acute coronary syndrome, it has become clear that this syndrome has unique clinical features that can readily be distinguished from acute infarction.In particular, in contrast to the irreversible myocardial injury seen with infarction, the myocardial dysfunction of SCM is completely reversible and occurs in the absence of plaque rupture and coronary thrombosis. There is increasing evidence that exaggerated sympathetic stimulation may play a pathogenic role in the development of SCM. Plasma catecholamine levels have been found to be markedly elevated in some patients with SCM, and the syndrome has been observed in other clinical states of catecholamine excess such as central neurologic injury and pheochromocytoma.Further, intravenous catecholamines can precipitate SCM in humans and can reproduce the syndrome in animal models. The precise mechanism in which excessive sympathetic stimulation may result in transient left ventricular dysfunction remains controversial. Abnormal myocardial blood flow due to sympathetically mediated microvascular dysfunction has been suggested and is supported by decreased coronary flow reserve during the acute phase of this syndrome. An alternative explanation is the direct effect of catecholamines on cardiac myocytes, possibly through cyclic AMP-mediated calcium overload. This manuscript will review the clinical and diagnostic features of SCM and will summarize the evidence supporting a sympathetically mediated pathogenesis. Clinical risk factors that appear to increase susceptibility to SCM, possibly by modulating myocyte and microvascular sensitivity to catecholamines, will also be highlighted. PMID- 22297545 TI - Different temporal patterns in the expressions of bone morphogenetic proteins and noggin during astroglial scar formation after ischemic stroke. AB - Bone morphogenetic proteins (BMPs) and their antagonists have roles in scar formation and regeneration after central nervous system injuries. However, temporal changes in their expression during astroglial scar formation in the ischemic brain are unknown. Here, we examined protein levels of BMP2, BMP7, and their antagonist noggin in the ischemic brain up to 4 weeks after experimental stroke in mice. BMP2 and BMP7 levels were increased from 1 to 4 weeks in the ischemic brain, and their expression was associated with astrogliosis. BMP7 expression was more intense and co-localized in reactive astrocytes in the ischemic subcortex at 1 week. Noggin expression began to increase after 2 weeks and was further increased at 4 weeks only in the ischemic subcortex, but the intensity was weak compared to the intensity of BMPs. Noggin was co-localized mainly in activated microglia. These findings show that expression of BMPs and noggin differed over time, in intensity and in types of cell, and suggest that BMPs and noggin have different roles in the processes of glial scar formation and neurorestoration in the ischemic brain. PMID- 22297546 TI - Biomarkers in public health. PMID- 22297547 TI - Serum biomarker profiles as diagnostic tools in lung cancer. AB - BACKGROUND: Computed tomography (CT) scanning has emerged as an effective means of early detection for lung cancer. Despite marked improvement over earlier methodologies, the low level of specificity demonstrated by CT scanning has limited its clinical implementation as a screening tool. A minimally-invasive biomarker-based test that could further characterize CT-positive patients based on risk of malignancy would greatly enhance its clinical efficacy. METHODS: We performed an analysis of 81 serum proteins in 92 patients diagnosed with lung cancer and 172 CT-screened control individuals. We utilize a series of bioinformatics algorithms including Metropolis-Monte Carlo, artificial neural networks, Naive Bayes, and additive logistic regression to identify multimarker panels capable of discriminating cases from controls with high levels of sensitivity and specificity in distinct training and independent validation sets. RESULTS: A three-biomarker panel comprised of MIF, prolactin, and thrombospondin identified using the Metropolis-Monte Carlo algorithm provided the best classification with a %Sensitivity/Specificity/Accuracy of 74/90/86 in the training set and 70/93/82 in the validation set. This panel was effective in the classification of control individuals demonstrating suspicious pulmonary nodules and stage I lung cancer patients. CONCLUSIONS: The selected serum biomarker panel demonstrated a high diagnostic utility in the current study and performance characteristics which compare favorably with previous reports. Further advancements may lead to the development of a diagnostic tool useful as an adjunct to CT-scanning. PMID- 22297548 TI - RASSF1A and CDH1 hypermethylation as potential epimarkers in breast cancer. AB - Breast cancer is the most common cancer in women worldwide, representing 28.2% of all female malignancies. In addition to genetic changes, epigenetic events, as aberrant DNA methylation and histone modification, are responsible for cancer development. Many tumour suppressor genes are inactivated by DNA hypermethylation, which could be utilized for identification of new epigenetic biomarkers. To investigate the relation between DNA methylation level and breast cancer progression, we analysed DNA methylation in RASSF1A and CDH1 promoters using quantitative multiplex methylation-specific PCR in paraffin-embedded tumour tissues and blood samples from 92 breast cancer patients and 50 controls, respectively. The associations between RASSF1A and CDH1 methylation levels and clinico-pathological parameters were tested by Kruskal-Wallis and van der Waerden ANOVA tests. Out of 92 breast cancer patients, 76 (82.6%) manifested various levels of RASSF1A (range from 1.20 to 92.63%) and 20 (21.7%) of CDH1 (range from 1.20 to 79.62%) methylation. However, no methylation was found in 50 controls. Increasing trends in RASSF1A methylation were observed in tumour size, lymph node status and TNM stage, but only CDH1 methylation levels showed statistically significant differences between the patient subgroups in lymph node status and IHC subtype. Overall, stable relatively high RASSF1A methylation could be utilised as universal tumour marker and the less frequent but highly methylated CDH1 promoter can serve for identification of potentially metastasising tumours. PMID- 22297549 TI - Confirmation of a potential biomarker for early-stage pancreatic cancer. AB - INTRODUCTION: Pancreatic cancer has a dismal prognosis because it is often diagnosed at an advanced stage. Therefore, serological biomarkers are eagerly sought for early detection. The digestive enzyme pro-carboxypeptidase A (PCPA) may be able to fill this role. The purpose of this study was to validate and extend previous research done at New York University (NYU), demonstrating that measurement of serum PCPA is a sensitive biomarker for early stage pancreatic cancer. MATERIALS AND METHODS: Samples were collected from 10 early and 16 late stage patients at Jersey Shore University Medical Center (JSUMC) and Robert Wood Johnson Hospital (RWJ) with adenocarcinoma of the head of the pancreas. RESULTS: The percentages of early and late stage cancer patients with PCPA values above the upper limit (2.35 u/L) were 90.0% and 56.0%, respectively. Mean PCPA values for early and late stage cancer were determined to be 22.95 u/L and 3.55 u/L, respectively. In one case, the prospective patient was detected by our assay one month before diagnosis. Additionally, data from an ampullary cancer patient supports the proposed mechanism behind this test. CONCLUSIONS: Combining the JSUMC and NYU results show 94% sensitivity, demonstrating that determining serum PCPA has the requisite sensitivity to detect early stage pancreatic cancer. PMID- 22297550 TI - Cortactin (CTTN) overexpression in osteosarcoma correlates with advanced stage and reduced survival. AB - BACKGROUND: The cortactin (CTTN) gene has been found, by transcriptomic profiling, to be overexpressed in pediatric osteosarcoma. The location of CTTN at 11q13 and the role of cortactin in cytoskeleton restructuring make CTTN of interest as a potential biomarker for osteosarcoma. MATERIALS AND METHODS: Osteoblasts were isolated from 20 high-grade osteosarcomas before chemotherapy, and paired with cell samples from normal tissue, prior to RNA expression analysis on HG-U133A chips (Affymetrix). Semiquantitative CTTN mRNA expression was analyzed by real-time PCR. An osteosarcoma tissue microarray (TMA) containing 233 tissue spots from 48 patients was used for an immunohistochemical (IHC) study of cortactin. RESULTS: Transcriptomic profiling and real-time PCR analysis indicated increased CTTN expression in osteosarcomas (p = 0.001, Student's T test). TMA IHC showed cortactin to be present more frequently and in greater abundance in osteosarcomas than non-tumoral osteoblastic samples (p< 0.006, Mann-Withney test). Analysis of clinical outcomes indicated that overall survival for patients with primary tumors positive for cortactin was significantly lower than that for patients with cortactin negative (or only weakly staining) tumors (p = 0.0278, Log-rank test). CONCLUSIONS: Our preliminary data support the hypothesis that over-expression of cortactin, contained in the 11q13 amplicon, is involved in osteosarcoma carcinogenesis. The potential of cortactin overexpression as a biomarker for osteosarcoma is consolidated. PMID- 22297551 TI - Correlation of serum biomarkers (TSA & LSA) and epithelial dysplasia in early diagnosis of oral precancer and oral cancer. AB - BACKGROUND: Oral cancer is currently the most frequent cause of cancer-related deaths, which is usually preceded by oral pre-cancerous lesions and conditions. Altered glycosylation of glycoconjugates, such as sialic acid, fucose, etc. are amongst the important molecular changes that accompany malignant transformation. The purpose of our study was to evaluate usefulness of serum Total Sialic Acid (TSA) and serum Lipid-Bound Sialic Acid (LSA) as markers of oral precancerous lesions and histopathologically correlating them with grades of epithelial dysplasia. METHODS: Blood samples were collected from 50 patients with oral precancer (Leukoplakia & OSMF), 25 patients with untreated oral cancer and 25 healthy subjects. Serum sialic acid (total and lipid bound) levels were measured spectrophotometrically. Tissue samples from all the patients were evaluated for dysplasia. RESULTS: Serum levels of total and lipid bound sialic acid were significantly elevated in patients with oral precancer and cancer when compared with healthy subjects. Analysis of variance test documented that there is progressive rise in serum levels of sialic acid with the degree of dysplastic changes in oral precancer patients. We observed positive correlation between serum levels of the markers and the extent of malignant disease (TNM Clinical staging) as well as histopathological grades. CONCLUSION: The results suggested that serum levels of TSA and LSA progressively increases with grades of dysplasia in precancerous groups and cancer group, when compared with healthy controls. These glycoconjugates, especially LSA has the clinical utility in indicating a premalignant change. PMID- 22297552 TI - Prognostic significance of beta-2 adrenergic receptor in oral squamous cell carcinoma. AB - The aim of this study was to evaluate the expression of beta2-adrenergic receptor (beta2-AR) in oral squamous cell carcinoma (OSCC) and to investigate the correlations between expression level and clinical characteristics, outcome, and patient prognosis. A total of 106 OSCC patients underwent surgical treatment at the A.C. Camargo Cancer Hospital, Sao Paulo, Brazil, were analyzed for clinicopathological data, treatment, tumor outcome, prognosis and immunohistochemical expression of beta2-AR. The beta2-AR expression was statistically analyzed relative to clinicopathological variables and survival using the Chi-square test, Kaplan-Meier curves and Cox regression model. Most OSCC (72.6%) exhibited malignant cells with strong cytoplasmatic and membranous beta2-AR expression. beta2-AR expression was significantly associated with alcohol (p = 0.021), simultaneous consumption of alcohol and tobacco (p = 0.014) and T stage (p = 0.07). In addition, OSCC patients who exhibited strong beta2-AR expression demonstrated a higher rate of overall survival (p = 0.001) and cancer specific survival (p = 0.004) compared to patients with weak/negative beta2-AR expression. The Cox regression model demonstrated that strong beta2-AR expression was an independent favorable prognostic factor for OSCC patients. These results suggest that the strong malignant cell beta2-AR expression is a favorable prognostic factor for OSCC patients and could be used as a target for new anti neoplastic pharmacological strategies. PMID- 22297553 TI - Long term intensive exercise training leads to a higher plasma malate/lactate dehydrogenase (M/L) ratio and increased level of lipid mobilization in horses. AB - Continuous high intensity training may induce alterations to enzyme activities related to glucose and lipid metabolism in horses. In our study, five Thoroughbred race horses (3 male and 2 female, avg age=5 yrs old) were compared against five riding horses (1 male, 1 female, 3 gelding, avg age=13 yrs old) in terms of energy metabolism, by examining plasma malate (MDH) and lactate (LDH) dehydrogenase activities and M/L ratio. MDH is involved in NADH and ATP generation, whereas LDH can convert NADH back into NAD(+) for ATP generation. An increase in plasma M/L ratio can reflect heightened energy metabolism in the liver and skeletal muscle of horses adapted to continuous intensive exercise. Moreover, plasma lipid metabolism analytes (adiponectin, NEFA, total cholesterol (T-Cho), and triglycerides (TG)) can reflect changes to lipolysis rate, which can also indicate a change in energy metabolism. Overall, race horses demonstrated increased MDH and LDH activity in plasma (4x and 2x greater, respectively), in addition to a plasma M/L ratio twice as high as that of riding horses (2.0 vs 1.0). In addition, race horses also demonstrated significantly higher levels of plasma NEFA (50% greater), TG (2x greater), and T-Cho (20% greater) as compared to riding horses. Therefore, race horse muscles may have adapted to prolonged high intensity endurance exercise by gaining a higher oxidative capacity and an increased capacity for fat utilization as an energy source, resulting in heightened energy metabolism and increased rate of lipid mobilization. PMID- 22297554 TI - A transgenic Marc-145 cell line of piggyBac transposon-derived targeting shRNA interference against porcine reproductive and respiratory syndrome virus. AB - Porcine reproductive and respiratory syndrome (PRRS) is now considered to be one of the most important diseases in countries with intensive swine industries. The two major membrane-associated proteins of porcine reproductive and respiratory syndrome virus (PRRSV), GP5 and M (encoded by ORF5 and ORF6 genes, respectively), are associated as disulfide-linked heterodimers (GP5/M) in the virus particle. In this study, we designed 5 of the small hairpin RNAs (shRNAs) targeting the GP5 and M gene of PRRSV respectively, and investigated their inhibition to the production of PRRSV. The highest activity displayed in shRNAs of the ORF6e sequence (nts 261-279), which the inhibition rate reached was 99.09%. The result suggests that RNAi technology might serve as a potential molecular strategy for PRRSV therapy. Furthermore, the transgenic Marc-145 cell line of piggyBac transposon-derived targeting shRNA interference against PRRS virus was established. It presented stable inhibition to the replication and amplification of PRRS. The work implied that shRNAs targeting the GP5 and M gene of PRRSV may be used as potential RNA vaccines in vivo, and supplied the screening methods of transformed pig embryonic fibroblast which are prerequisite for the disease resistant transgenic pigs to PRRS. PMID- 22297555 TI - Replicability of structural models of the Edinburgh Postnatal Depression Scale (EPDS) in a community sample of postpartum African American women with low socioeconomic status. AB - The Edinburgh Postnatal Depression Scale (EPDS) is increasingly used in public health and social service programs serving postpartum women of racially, ethnically, and socioeconomically diverse backgrounds at risk for depression. However, we know little about its factor structure across groups of women with implications for measuring symptom levels in research. This study evaluated the underlying structure of the EPDS using a confirmatory factor analyses model comparison approach of five factor models from the literature in a purposive community sample of 169 postpartum African American women of low socioeconomic status. Participants were identified through an exhaustive review of local health department program files dated August 2006 to August 2010 in a Midwestern state of USA. Tuohy and McVey's (Br JClin Psychol 47:153-169, 2008) three-factor model (depression, anxiety, and anhedonia) demonstrated the best fit to the data with a nonsignificant Satora-Bentler scaled chi-square value (21.70, df024, p00.60) and the lowest root mean square error of approximation (0.00) and standardized root mean square residual (0.05) values. The results call for further study of the factor structure of the EPDS in other racial and ethnic groups and cautious use of the EPDS among perinatal women of racially, ethnically, and socioeconomically diverse backgrounds until its factorial invariance is better understood. PMID- 22297556 TI - Structure, fluctuation and magnitude of a natural grassland soil metagenome. AB - The soil ecosystem is critical for human health, affecting aspects of the environment from key agricultural and edaphic parameters to critical influence on climate change. Soil has more unknown biodiversity than any other ecosystem. We have applied diverse DNA extraction methods coupled with high throughput pyrosequencing to explore 4.88 * 10(9) bp of metagenomic sequence data from the longest continually studied soil environment (Park Grass experiment at Rothamsted Research in the UK). Results emphasize important DNA extraction biases and unexpectedly low seasonal and vertical soil metagenomic functional class variations. Clustering-based subsystems and carbohydrate metabolism had the largest quantity of annotated reads assigned although <50% of reads were assigned at an E value cutoff of 10(-5). In addition, with the more detailed subsystems, cAMP signaling in bacteria (3.24+/-0.27% of the annotated reads) and the Ton and Tol transport systems (1.69+/-0.11%) were relatively highly represented. The most highly represented genome from the database was that for a Bradyrhizobium species. The metagenomic variance created by integrating natural and methodological fluctuations represents a global picture of the Rothamsted soil metagenome that can be used for specific questions and future inter-environmental metagenomic comparisons. However, only 1% of annotated sequences correspond to already sequenced genomes at 96% similarity and E values of <10(-5), thus, considerable genomic reconstructions efforts still have to be performed. PMID- 22297558 TI - Detection of tPA-induced hyperfibrinolysis in whole blood by RapidTEG, KaolinTEG, and functional fibrinogenTEG in healthy individuals. AB - BACKGROUND: Rapid identification of clinically relevant coagulopathies in, acute coagulopathy of trauma shock (ACOTS) has led to the development of faster point of-care viscoelastic whole-blood-based tests like rapid thrombelastography (RapidTEG). The sensitivity of RapidTEG to detect hyperfibrinolysis, as compared to standard KaolinTEG, is unknown. To investigate this, the ability of RapidTEG, KaolinTEG, and functional fibrinogenTEG (FFTEG) to detect tPA-induced (tissue plasminogen activator) lysis in whole blood from healthy individuals was investigated. Our hypothesis was that the initial powerful clot formation in the RapidTEG assay would reduce the sensitivity as compared to the normally used KaolinTEG assay. We also evaluated the FFTEG assay. METHODS: In vitro comparison of the sensitivity of RapidTEG, KaolinTEG, and FFTEG to 1.8 nmol/L tPA in citrated whole blood (299 +/- 23 ng/mL plasma) induced hyperfibrinolysis in 10 healthy individuals and duplicate titration of the tPA whole blood (WB) concentration from 0.09 to 7.2 nmol/L (14-1144 ng/mL plasma) in 1 healthy donor. RESULTS: At 1.8 nmol/L tPA, KaolinTEG, RapidTEG, and FFTEG all detected fibrinolysis but with different sensitivities. In the titration study, KaolinTEG and FFTEG displayed a continuous dose-response association and RapidTEG also displayed a dose-dependent response but only for higher levels of tPA, thus yielding a smaller "dose-sensitive range" compared to KaolinTEG and FFTEG. CONCLUSION: This pilot study demonstrated that KaolinTEG, RapidTEG, and FFTEG all were able to detect lysis at 1.8 nmol/L tPA but with a difference in sensitivity. Furthermore, KaolinTEG and FFTEG showed a continuous dose dependence related to the tPA concentration, whereas RapidTEG only detected lysis at higher tPA concentrations. PMID- 22297557 TI - Metaproteogenomic analysis of a community of sponge symbionts. AB - Sponges harbour complex communities of diverse microorganisms, which have been postulated to form intimate symbiotic relationships with their host. Here we unravel some of these interactions by characterising the functional features of the microbial community of the sponge Cymbastela concentrica through a combined metagenomic and metaproteomic approach. We discover the expression of specific transport functions for typical sponge metabolites (for example, halogenated aromatics, dipeptides), which indicates metabolic interactions between the community and the host. We also uncover the simultaneous performance of aerobic nitrification and anaerobic denitrification, which would aid to remove ammonium secreted by the sponge. Our analysis also highlights the requirement for the microbial community to respond to variable environmental conditions and hence express an array of stress protection proteins. Molecular interactions between symbionts and their host might also be mediated by a set of expressed eukaryotic like proteins and cell-cell mediators. Finally, some sponge-associated bacteria (for example, a Phyllobacteriaceae phylotype) appear to undergo an evolutionary adaptation process to the sponge environment as evidenced by active mobile genetic elements. Our data clearly show that a combined metaproteogenomic approach can provide novel information on the activities, physiology and interactions of sponge-associated microbial communities. PMID- 22297559 TI - Smaller platelet volumes associated with vascular malformations. AB - Various parameters in 91 adult participants with vascular malformations and 91 controls were studied. The mean of the participants' platelet volumes was 8.5 fL and that of their controls was 9.1 (P < .001). The mean of the participants' platelet mass was 2145 uL/L of blood and that of their controls was 2351 (P = .006). The other parameters studied were not significantly different than the controls. It is suggested that the lower platelet volume might be related to a compensatory mechanism to keep the total body platelet mass stable despite the increased vasculature. PMID- 22297560 TI - Protein Z concentrations in patients with acute leukemia. AB - Protein Z (PZ) deficiency may induce bleeding as well as thrombosis. The aim of our study was to estimate the concentration of PZ in patients with acute leukemia. Plasma levels of PZ were determined in 76 patients with newly diagnosed acute leukemia ([AML], n = 50; acute lymphoblastic leukemia [ALL], n = 26) and 62 healthy participants. In the patients, mean plasma concentrations of PZ were statistically lower than in healthy individuals: AML (1.24 +/- 0.11 MUg/mL vs 1.58 +/- 0.05 MUg/mL P = .01) and ALL (1.19 +/- 0.16 MUg/mL vs 1.58 +/- 0.05 MUg/mL P = .01). Levels of PZ below the fifth percentile (0.873 MUg/mL) of normal value distribution in control participants were found in 30% of patients with AML and ALL and in 3% of controls (P < .0001). In this AML subgroup, we found statistically significant correlation between episodes of bleeding and PZ level (P = .01). There was no such correlation in ALL group. The results suggest that PZ can be a cofactor associated with an increased bleeding tendency in patients with AML. PMID- 22297561 TI - Macrothrombocytopenia/stomatocytosis specially associated with phytosterolemia. AB - Phytosterolemia is a rare autosomal recessive disease of plant sterol metabolism, the pathophysiological features of which are high plasma levels of plant sterols and xanthomatosis caused by mutations of ABCG5 and ABCG8 genes, and the combination of hemolysis and macrothrombocytopenia is an unusual clinical manifestation. All the patients of the 3 unrelated phytosterolemia first presented with prominent macrothrombocytopenia and stomatocytosis. They were either homozygous or compound heterozygous for ABCG5/ABCG8 gene mutations and had significantly elevated serum plant sterols levels quantified using high performance liquid chromatography. The in vitro study demonstrated that sitosterol can cause changes in shape and osmotic fragility of red blood cells. These findings suggest that macrothrombocytopenia and stomatocytosis could be initial and main features in some patients with phytosterolemia and that serum phytosterols and relevant genes should be analyzed in patients whose macrothrombocytopenia and/or stomatocytosis are unexplained, especially whose parents are of consanguineous marriage. PMID- 22297562 TI - An expectation and maximization algorithm for estimating Q X E interaction effects. AB - A Markov chain Monte Carlo (MCMC) implemented Bayesian method has been developed to detect quantitative trait loci (QTL) effects and Q x E interaction effects. However, the MCMC algorithm is time consuming due to repeated samplings of QTL parameters. We developed an expectation and maximization (EM) algorithm as an alternative method for detecting QTL and Q x E interaction. Simulation studies and real data analysis showed that the EM algorithm produced comparable result as the Bayesian method, but with a speed many magnitudes faster than the MCMC algorithm. We used the EM algorithm to analyze a well known barley dataset produced by the North American Barley Genome Mapping Project. The dataset contained eight quantitative traits collected from 150 doubled-haploid (DH) lines evaluated in multiple environments. Each line was genotyped for 495 polymorphic markers. The result showed that all eight traits exhibited QTL main effects and Q x E interaction effects. On average, the main effects and Q x E interaction effects contributed 34.56 and 16.23% of the total phenotypic variance, respectively. Furthermore, we found that whether or not a locus shows Q x E interaction does not depend on the presence of main effect. PMID- 22297563 TI - Studying the genetic basis of drought tolerance in sorghum by managed stress trials and adjustments for phenological and plant height differences. AB - Managed environments in the form of well watered and water stressed trials were performed to study the genetic basis of grain yield and stay green in sorghum with the objective of validating previously detected QTL. As variations in phenology and plant height may influence QTL detection for the target traits, QTL for flowering time and plant height were introduced as cofactors in QTL analyses for yield and stay green. All but one of the flowering time QTL were detected near yield and stay green QTL. Similar co-localization was observed for two plant height QTL. QTL analysis for yield, using flowering time/plant height cofactors, led to yield QTL on chromosomes 2, 3, 6, 8 and 10. For stay green, QTL on chromosomes 3, 4, 8 and 10 were not related to differences in flowering time/plant height. The physical positions for markers in QTL regions projected on the sorghum genome suggest that the previously detected plant height QTL, Sb-HT9 1, and Dw2, in addition to the maturity gene, Ma5, had a major confounding impact on the expression of yield and stay green QTL. Co-localization between an apparently novel stay green QTL and a yield QTL on chromosome 3 suggests there is potential for indirect selection based on stay green to improve drought tolerance in sorghum. Our QTL study was carried out with a moderately sized population and spanned a limited geographic range, but still the results strongly emphasize the necessity of corrections for phenology in QTL mapping for drought tolerance traits in sorghum. PMID- 22297564 TI - Inheritance of long staple fiber quality traits of Gossypium barbadense in G. hirsutum background using CSILs. AB - Gossypium hirsutum is a high yield cotton species that exhibits only moderate performance in fiber qualities. A promising but challenging approach to improving its phenotypes is interspecific introgression, the transfer of valuable traits or genes from the germplasm of another species such as G. barbadense, an important cultivated extra long staple cotton species. One set of chromosome segment introgression lines (CSILs) was developed, where TM-1, the genetic standard in G. hirsutum, was used as the recipient parent and the long staple cotton G. barbadense Hai7124 was used as the donor parent by molecular marker-assisted selection (MAS) in BC(5)S(1-4) and BC(4)S(1-3) generations. After four rounds of MAS, the CSIL population was comprised of 174 lines containing 298 introgressed segments, of which 86 (49.4%) lines had single introgressed segments. The total introgressed segment length covered 2,948.7 cM with an average length of 16.7 cM and represented 83.3% of tetraploid cotton genome. The CSILs were highly varied in major fiber qualities. By integrated analysis of data collected in four environments, a total of 43 additive quantitative trait loci (QTL) and six epistatic QTL associated with fiber qualities were detected by QTL IciMapping 3.0 and multi-QTL joint analysis. Six stable QTL were detected in various environments. The CSILs developed and the analyses presented here will enhance the understanding of the genetics of fiber qualities in long staple G. barbadense and facilitate further molecular breeding to improve fiber quality in Upland cotton. PMID- 22297565 TI - Lr68: a new gene conferring slow rusting resistance to leaf rust in wheat. AB - The common wheat cultivar Parula possesses a high level of slow rusting, adult plant resistance (APR) to all three rust diseases of wheat. Previous mapping studies using an Avocet-YrA/Parula recombinant inbred line (RIL) population showed that APR to leaf rust (Puccinia triticina) in Parula is governed by at least three independent slow rusting resistance genes: Lr34 on 7DS, Lr46 on 1BL, and a previously unknown gene on 7BL. The use of field rust reaction and flanking markers identified two F(6) RILs, Arula1 and Arula2, from the above population that lacked Lr34 and Lr46 but carried the leaf rust resistance gene in 7BL, hereby designated Lr68. Arula1 and Arula2 were crossed with Apav, a highly susceptible line from the cross Avocet-YrA/Pavon 76, and 396 F(4)-derived F(5) RILs were developed for mapping Lr68. The RILs were phenotyped for leaf rust resistance for over 2 years in Ciudad Obregon, Mexico, with a mixture of P. triticina races MBJ/SP and MCJ/SP. Close genetic linkages with several DNA markers on 7BL were established using 367 RILs; Psy1-1 and gwm146 flanked Lr68 and were estimated at 0.5 and 0.6 cM, respectively. The relationship between Lr68 and the race-specific seedling resistance gene Lr14b, located in the same region and present in Parula, Arula1 and Arula2, was investigated by evaluating the RILs with Lr14b-avirulent P. triticina race TCT/QB in the greenhouse. Although Lr14b and Lr68 homozygous recombinants in repulsion were not identified in RILs, gamma irradiation-induced deletion stocks that lacked Lr68 but possessed Lr14b showed that Lr68 and Lr14b are different loci. Flanking DNA markers that are tightly linked to Lr68 in a wide array of genotypes can be utilized for selection of APR to leaf rust. PMID- 22297567 TI - Influence of supervision ratios by anesthesiologists on first-case starts and critical portions of anesthetics. AB - BACKGROUND: Anesthesia groups may wish to decrease the supervision ratio for nontrainee providers. Because hospitals offer many first-case starts and focus on starting these cases on time, the number of anesthesiologists needed is sensitive to this ratio. The number of operating rooms that an anesthesiologist can supervise concurrently is determined by the probability of multiple simultaneous critical portions of cases (i.e., requiring presence) and the availability of cross-coverage. A simulation study showed peak occurrence of critical portions during first cases, and frequent supervision lapses. These predictions were tested using real data from an anesthesia information management system. METHODS: The timing and duration of critical portions of cases were determined from 1 yr of data at a tertiary care hospital. The percentages of days with at least one supervision lapse occurring at supervision ratios between 1:1 and 1:3 were determined. RESULTS: Even at a supervision ratio of 1:2, lapses occurred on 35% of days (lower 95% confidence limit = 30%). The peak incidence occurred before 8:00 AM, P < 0.0001 for the hypothesis that most (i.e., >50%) lapses occurred before this time. The average time from operating room entry until ready for prepping and draping (i.e., anesthesia release time) during first case starts was 22.2 min (95% confidence interval 21.8-22.8 min). CONCLUSIONS: Decreasing the supervision ratio from 1:2 to 1:3 has a large effect on supervision lapses during first-case starts. To mitigate such lapses, either staggered starts or additional anesthesiologists working at the start of the day would be required. PMID- 22297566 TI - The entirely carbohydrate immunogen Tn-PS A1 induces a cancer cell selective immune response and cytokine IL-17. AB - The tumor-associated carbohydrate antigen/hapten Thomsen-nouveau (Tn; a-D-GalpNAc ONH2) was conjugated to a zwitterionic capsular polysaccharide, PS A1, from commensal anaerobe Bacteroides fragilis ATCC 25285/NCTC 9343 for the development of an entirely carbohydrate cancer vaccine construct and probed for immunogenicity. This communication discloses that murine anti-Tn IgG3 antibodies both bind to and recognize human tumor cells that display the Tn hapten. Furthermore, the sera from immunization of mice with Tn-PS A1 contain cytokine interleukin 17 (IL-17A), which is known to possess anti-tumor function and represents a striking difference to an IL-2, and IL-6 profile obtained with anti PS A1 sera. PMID- 22297568 TI - Antiviral effect of maraviroc in semen: a case report. AB - We describe the antiviral effect of maraviroc in a patient who had been shedding high levels of HIV-1 in seminal fluid for three years despite an undetectable blood plasma viral load. Adding maraviroc to HAART stopped the seminal shedding. We discuss the mechanisms involved and the effect on sexual transmission. PMID- 22297569 TI - Tandem deuteration/hydrosilylation reactions catalyzed by a rhodium carbene complex under solvent-free conditions. AB - The complex [Rh(I(t)Bu)(2)HCl] has been shown to be an active catalyst in the hydrosilylation of carbonyl and imine complexes. This reactivity, combined with the previously reported H/D exchange catalyzed by these complexes allows for a one pot, two step reaction using a single catalyst for both H/D exchange and hydrosilylation. Using triethylsilane, [Rh(I(t)Bu)(2)Cl] catalyst, and D(2) gas, deuterated silyl-ethers can be synthesized in an atom-economical, solvent-free reaction. PMID- 22297571 TI - De novo acute myeloid leukemia risk factors: a Texas case-control study. AB - BACKGROUND: Acute myeloid leukemia (AML) is comprised of several bone marrow based cancers and is the most common type of leukemia in the United States. The etiology of AML is not well understood. A case-control study was conducted at The University of Texas M. D. Anderson Cancer Center to investigate associations between lifestyle characteristics and the risk of AML in Texas. METHODS: This study included 638 adult patients with de novo AML (cases) and a group of 636 matched controls. Interviewer-administered questionnaires were used to collect demographic and occupational data. The distribution of cases by World Health Organization (WHO) subtype was 71 patients (11%) with recurrent cytogenetic abnormalities (AML-RCA), 134 patients (21%) with multilineage dysplasia (AML-MD), and 389 patients (61%) with AML not otherwise categorized (AML-NOC). Multivariate logistic regression analyses were performed among all AML cases and among both sexes and each WHO subgroup. RESULTS: Among men, heavy smoking (>=30 pack-years; odds ratio [OR], 1.86) and occupational solvent exposure at low levels (OR, 2.87) or moderate/high levels (OR, 4.13) statistically significantly increased the risk of AML. Among women, obesity (OR, 1.62) and solvent exposure to low levels (OR, 2.73) or moderate/high levels (OR, 3.90) increased the risk of AML. Across WHO subtypes, obesity was associated with a statistically significantly increased risk of AML-RCA (OR, 3.15), whereas solvent exposure increased the risk in all subtypes at low levels (AML-RCA: OR, 4.11; AML-MD: OR, 2.54) and moderate/high levels (AML-RCA: OR, 5.13; AML-MD: OR, 3.02). A joint effect between smoking and solvent exposure was observed, and the highest risk was observed among smokers who had solvent exposure (OR, 4.51). CONCLUSIONS: The current results suggested that several factors play a role in AML predisposition with possible joint effects. Risk profiles for AML differed by sex and WHO subtype. PMID- 22297572 TI - An Evaluation of Navigational Ability Comparing Redirected Free Exploration with Distractors to Walking-in-Place and Joystick Locomotion Interfaces. AB - We report on a user study evaluating Redirected Free Exploration with Distractors (RFED), a large-scale, real-walking, locomotion interface, by comparing it to Walking-in-Place (WIP) and Joystick (JS), two common locomotion interfaces. The between-subjects study compared navigation ability in RFED, WIP, and JS interfaces in VEs that are more than two times the dimensions of the tracked space. The interfaces were evaluated based on navigation and wayfinding metrics and results suggest that participants using RFED were significantly better at navigating and wayfinding through virtual mazes than participants using walking in-place and joystick interfaces. Participants traveled shorter distances, made fewer wrong turns, pointed to hidden targets more accurately and more quickly, and were able to place and label targets on maps more accurately. Moreover, RFED participants were able to more accurately estimate VE size. PMID- 22297573 TI - Histone deacetylases 2 and 9 are coexpressed and nuclear localized in human molar odontoblasts in vivo. AB - Histone deacetylases (HDACs) are components of nuclear multiprotein complexes that deacetylate histones and perform important roles in repression of transcription.Using specific rabbit mAbs, we analyzed by immune histochemistry and confocal immunofluorescence analysis the expression and subcellular localization of HDAC1-4 and HDAC9 in sections of adult human third molars. HDAC2 and HDAC9 were expressed in some pulpal cells and strongly expressed in the majority of mature odontoblasts.In contrast, only weak expression of HDAC1, HDAC3 and HDAC4 was observed. Confocal immunofluorescence analysis together with the DNA stain DRAQ5 revealed that HDAC2 and HDAC9 were coexpressed within the odontoblast nucleus, but localized to distinct subnuclear structures.In contrast to the current point of view, HDAC2 is strongly expressed in a terminally differentiated cell type.Our results imply that class I and II HDACs are involved in the transcriptional regulation of human odontoblasts in vivo. PMID- 22297574 TI - Determinants of 2009 A/H1N1 influenza vaccination among pregnant women in Hong Kong. AB - During the 2009-2010 A/H1N1 influenza pandemic, pregnant women infected with the virus experienced excess morbidity and mortality when compared with other groups. Once a vaccine was available, pregnant women were a priority group for vaccination. Only a few studies have reported on the uptake of 2009 A/H1N1 influenza vaccine among pregnant women during the pandemic and none were from Asia. The purpose of this study was to examine factors associated with 2009 A/H1N1 influenza vaccine uptake among pregnant women in Hong Kong. Using a multi center, cross-sectional design, we recruited 549 postpartum women from four post natal wards in Hong Kong over a 4-month period during the second wave of the A/H1N1 influenza pandemic in the winter and spring of 2010. Only 6.2% (n = 34) of participants had received the 2009 A/H1N1 influenza vaccine and 4.9% (n = 27) had received the seasonal influenza vaccine. The most common reasons for not receiving the 2009 A/H1N1 vaccine were fear of causing harm to themselves or their fetus. A high knowledge level (OR = 19.06; 95% CI 5.55, 65.48), more positive attitudes (OR = 3.52; 95% CI 1.37, 9.07), and having a family member who had the 2009 A/H1N1 influenza vaccine (OR = 7.69; 95% CI 2.92, 20.19) were independently and positively associated with vaccination. Study results show an unacceptably low uptake of the pandemic A/H1N1 influenza vaccine among pregnant women in Hong Kong. Interventions to increase influenza vaccine knowledge and uptake among this group should be a priority for future pandemic planning and seasonal vaccination campaigns. PMID- 22297575 TI - Forward genetic approaches to understanding complex behaviors. AB - Assigning function to genes has long been a focus of biomedical research.Even with complete knowledge of the genomic sequences of humans, mice and other experimental organisms, there is still much to be learned about gene function and control. Ablation or overexpression of single genes using knockout or transgenic technologies has provided functional annotation for many genes, but these technologies do not capture the extensive genetic variation present in existing experimental mouse populations. Researchers have only recently begun to truly appreciate naturally occurring genetic variation resulting from single nucleotide substitutions,insertions, deletions, copy number variation, epigenetic changes (DNA methylation,histone modifications, etc.) and gene expression differences and how this variation contributes to complex phenotypes. In this chapter, we will discuss the benefits and limitations of different forward genetic approaches that capture the genetic variation present in inbred mouse strains and present the utility of these approaches for mapping QTL that influence complex behavioral phenotypes. PMID- 22297577 TI - Graphene oxide modified TiO2 nanotube arrays: enhanced visible light photoelectrochemical properties. AB - Novel nanocomposite films, based on graphene oxide (GO) and TiO(2) nanotube arrays, were synthesized by assembling GO on the surface of self-organized TiO(2) nanotube arrays through a simple impregnation method. The composite films were characterized with field emission scanning electron microscopy, X-ray diffraction, Raman spectroscopy and UV-vis diffuse reflectance spectroscopy. The photoelectrochemical properties of the composite nanotube arrays were investigated under visible light illumination. Remarkably enhanced visible light photoelectrochemical response was observed for the GO decorated TiO(2) nanotube composite electrode compared with pristine TiO(2) nanotube arrays. The sensitizing effect of GO on the photoelectrochemical response of the TiO(2) nanotube arrays was demonstrated and about 15 times enhanced maximum photoconversion efficiency was obtained with the presence of GO. An enhanced photocatalytic activity of the TiO(2) nanotube arrays towards the degradation of methyl blue was also demonstrated after modification with GO. The results presented here demonstrate GO to be efficient for the improved utilization of visible light for TiO(2) nanotube arrays. PMID- 22297578 TI - Central apnea after adenotonsillectomy in childhood: case report. PMID- 22297579 TI - Quantitative live cell fluorescence-microscopy analysis of fission yeast. AB - Several microscopy techniques are available today that can detect a specific protein within the cell. During the last decade live cell imaging using fluorochromes like Green Fluorescent Protein (GFP) directly attached to the protein of interest has become increasingly popular. Using GFP and similar fluorochromes the subcellular localisations and movements of proteins can be detected in a fluorescent microscope. Moreover, also the subnuclear localisation of a certain region of a chromosome can be studied using this technique. GFP is fused to the Lac Repressor protein (LacR) and ectopically expressed in the cell where tandem repeats of the lacO sequence has been inserted into the region of interest on the chromosome. The LacR-GFP will bind to the lacO repeats and that area of the genome will be visible as a green dot in the fluorescence microscope. Yeast is especially suited for this type of manipulation since homologous recombination is very efficient and thereby enables targeted integration of the lacO repeats and engineered fusion proteins with GFP. Here we describe a quantitative method for live cell analysis of fission yeast. Additional protocols for live cell analysis of fission yeast can be found, for example on how to make a movie of the meiotic chromosomal behaviour. In this particular experiment we focus on subnuclear organisation and how it is affected during gene induction. We have labelled a gene cluster, named Chr1, by the introduction of lacO binding sites in the vicinity of the genes. The gene cluster is enriched for genes that are induced early during nitrogen starvation of fission yeast. In the strain the nuclear membrane (NM) is labelled by the attachment of mCherry to the NM protein Cut11 giving rise to a red fluorescent signal. The Spindle Pole body (SPB) compound Sid4 is fused to Red Fluorescent Protein (Sid4-mRFP). In vegetatively growing yeast cells the centromeres are always attached to the SPB that is embedded in the NM. The SPB is identified as a large round structure in the NM. By imaging before and 20 minutes after depletion of the nitrogen source we can determine the distance between the gene cluster (GFP) and the NM/SPB. The mean or median distances before and after nitrogen depletion are compared and we can thus quantify whether or not there is a shift in subcellular localisation of the gene cluster after nitrogen depletion. PMID- 22297580 TI - Unresolved attachment status and trauma-related symptomatology in maltreated adolescents: an examination of cognitive mediators. AB - Attachment Theory has received increasing interest as a framework allowing for a more refined understanding of the potential consequences of early relational trauma on psychological and social adjustment. Research has provided support for the role of disorganized attachment, both as a sequela of traumatic experiences and as a risk factor for subsequent maladjustment. This study investigated the associations between unresolved/disorganized attachment, cognitive functioning, and dissociative symptomatology in a sample of 60 adolescents with a history of maltreatment. A model with cognitive efficiency as a mediator variable was tested using hierarchical multiple regression analysis, with a bootstrapping procedure to examine indirect effects. Results provided support for the association between unresolved attachment, cognitive efficiency (but not verbal or thinking ability), and dissociation. Working memory was a strong mediator of the link between attachment and dissociation. These results highlight the importance of assessing attachment status and cognitive functioning in the context of clinical work with maltreated youth. In addition, it is proposed that greater attention be paid to internal models of attachment relationships and how they impact psychosocial functioning at different levels in maltreated populations. PMID- 22297581 TI - Time dynamics of autoantibodies are coupled to phenotypes and add to the heterogeneity of autoimmune diabetes in adults: the HUNT study, Norway. AB - AIMS: The aetiology of latent autoimmune diabetes in adults (LADA), assessed by autoimmune markers, is insufficiently clarified. We cross-sectionally investigated the prevalence and prospectively the prediabetic and postdiabetic presence of antibodies to glutamic acid decarboxylase (GADA), insulinoma associated protein 2 and zinc transporter 8 in LADA and in type 1 diabetes. METHODS: We included 208 'classic' type 1, 161 LADA and 302 type 2 diabetic cases from the second (HUNT2: 1995-1997) and third (HUNT3: 2006-2008) Nord-Trondelag health surveys. Prospective data were available for 59 type 1, 44 LADA and 302 type 2 diabetic cases followed from HUNT2 to HUNT3. From HUNT3, 24 type 1 diabetic and 31 LADA incident cases were available. RESULTS: Cross-sectionally, 90% of LADA cases were positive for only one antibody (10% multiple antibodypositive). Prospectively, 59% of GADA-positive LADA patients in HUNT2 were no longer positive in HUNT3. LADA patients who became negative possessed less frequently risk HLA haplotypes and were phenotypically more akin to those with type 2 diabetes than to those who stayed positive. Still, those losing positivity differed from those with type 2 diabetes by lower C-peptide levels (p = 0.009). Of incident LADA cases in HUNT3, 64% were already antibody-positive in HUNT2, i.e. before diabetes diagnosis. These incident LADA cases were phenotypically more akin to type 1 diabetes than were those who did not display positivity in HUNT2. CONCLUSION/INTERPRETATION: The pattern of antibodies, the postdiabetic loss or persistence as well as the prediabetic absence or presence of antibodies influence LADA phenotypes. Time-dependent presence or absence of antibodies adds new modalities to the heterogeneity of LADA. PMID- 22297576 TI - Behavioral and pharmacogenetics of aggressive behavior. AB - Serotonin (5-HT) has long been considered as a key transmitter in the neurocircuitry controlling aggression. Impaired regulation of each subtype of 5 HT receptor, 5-HT transporter, synthetic and metabolic enzymes has been linked particularly to impulsive aggression. The current summary focuses mostly on recent findings from pharmacological and genetic studies. The pharmacological treatments and genetic manipulations or polymorphisms of aspecific target (e.g., 5-HT1A receptor) can often result in inconsistent results on aggression, due to "phasic" effects of pharmacological agents versus "trait"-like effects of genetic manipulations. Also, the local administration of a drug using the intracranial microinjection technique has shown that activation of specific subtypes of 5-HT receptors (5-HT1A and 5-HT1B) in mesocorticolimbic areas can reduce species typical and other aggressive behaviors, but the same receptors in the medial prefrontal cortex or septal area promote escalated forms of aggression. Thus, there are receptor populations in specific brain regions that preferentially modulate specific types of aggression. Genetic studies have shown important gene environment interactions; it is likely that the polymorphisms in the genes of 5 HT transporters or rate-limiting synthetic and metabolic enzymes of 5-HT (e.g., MAOA) determine the vulnerability to adverse environmental factors that escalate aggression. We also discuss the interaction between the 5-HT system and other systems. Modulation of 5-HT neurons in the dorsalraphe nucleus by GABA, glutamate and CRF profoundly regulate aggressive behaviors. Also, interactions of the 5-HT system with other neuropeptides(arginine vasopressin, oxytocin, neuropeptide Y, opioid) have emerged as important neurobiological determinants of aggression. Studies of aggression in genetically modified mice identified several molecules that affect the 5-HT system directly (e.g., Tph2, 5-HT1B, 5-HT transporter, Pet1, MAOA) or indirectly[e.g., BDNF, neuronal nitric oxide (nNOS), aCaMKII, Neuropeptide Y].The future agenda delineates specific receptor subpopulations for GABA, glutamate and neuropeptides as they modulate the canonical aminergic neurotransmitters in brainstem, limbic and cortical regions with the ultimate outcome of attenuating or escalating aggressive behavior. PMID- 22297583 TI - Impact of diabetes and glycaemic control on peripheral artery disease in Japanese patients with end-stage renal disease: long-term follow-up study from the beginning of haemodialysis. AB - AIMS/HYPOTHESIS: End-stage renal disease (ESRD) patients with diabetes have been regarded as being at the highest risk of cardiovascular disease. We therefore investigated the relationship between diabetes and the incidence of peripheral artery disease (PAD) in new haemodialysis patients. METHODS: We enrolled 1,513 ESRD patients who had just begun haemodialysis therapy. They were divided into two groups: those with (n = 739) and those without diabetes (n = 774). The endpoint was the development of PAD, defined as ankle brachial pressure index <= 0.9 or toe brachial pressure index <0.7 in patients with an ankle brachial pressure index >0.9. RESULTS: According to the Kaplan-Meier method, the 10 year event-free rate for development of PAD and lower limb amputation was significantly lower in the diabetes group than in the non-diabetes group (60.3% vs 82.8%, HR 2.99, 95% CI 2.27, 3.92, p<0.0001 and 93.9% vs 98.9%, HR 5.59, 95% CI 2.14, 14.7, p = .0005 for PAD and lower limb amputation, respectively). In patients with diabetes, quartile analysis of HbA1c levels showed that the highest quartile group (>= 6.8% [51 mmol/mol]) had significant development of PAD and lower limb amputation compared with lower quartile groups (PAD HR 1.63, 95% CI 1.17, 2.28, p = .0038; lower limb amputation HR 2.99, 95% CI 1.17, 7.70, p = .023). CONCLUSIONS/INTERPRETATION: Diabetes was a strong predictor of PAD after initiation of haemodialysis therapy in patients with ESRD. In addition, higher HbA1c levels were associated with increased risk of developing PAD and requiring limb amputation in such diabetic populations. PMID- 22297584 TI - Is FTO a type 2 diabetes susceptibility gene? PMID- 22297585 TI - Negative childhood experiences and mental health: theoretical, clinical and primary prevention implications. AB - After decades of ignoring or minimising the prevalence and effects of negative events in childhood, researchers have recently established that a broad range of adverse childhood events are significant risk factors for most mental health problems, including psychosis. Researchers are now investigating the biological and psychological mechanisms involved. In addition to the development of a traumagenic neurodevelopmental model for psychosis, the exploration of a range of psychological processes, including attachment and dissociation, is shedding light on the specific aetiologies of discrete phenomena such as hallucinations and delusions. It is argued that the theoretical, clinical and primary prevention implications of our belated focus on childhood are profound. PMID- 22297586 TI - Antibody-mediated encephalitis: a treatable cause of schizophrenia. AB - Psychiatrists need to be vigilant for the newly recognised and treatable disorder of antibody-mediated encephalitis. Psychiatric symptoms are common, and individuals with the disorder often present initially to psychiatric services. We describe the clinical features of the disorder and make recommendations for further investigations. PMID- 22297587 TI - Setting the bar: athletes and vulnerability to mental illness. AB - Whereas physical sport activity is generally considered a health benefit, extreme exercise may be harmful. Of particular concern in this regard is the considerable variation between doctors in the primary care setting and those working within the sports setting around the diagnosis and treatment of athletes presenting with similar symptoms. Known risk factors for athletes are herein presented to raise awareness of the negative side of sport and to bring attention to the psychological outcomes and needs of athletes. The need for research into the incidence and aetiology of mental illness within elite level sport is also raised. PMID- 22297588 TI - Putting the efficacy of psychiatric and general medicine medication into perspective: review of meta-analyses. AB - BACKGROUND: The efficacy of psychopharmacological treatments has been called into question. Psychiatrists are unfamiliar with the effectiveness of common medical drugs. AIMS: To put the efficacy of psychiatric drugs into the perspective of that of major medical drugs. METHOD: We searched Medline and the Cochrane Library for systematic reviews on the efficacy of drugs compared with placebo for common medical and psychiatric disorders, and systematically presented the effect sizes for primary efficacy outcomes. RESULTS: We included 94 meta-analyses (48 drugs in 20 medical diseases, 16 drugs in 8 psychiatric disorders). There were some general medical drugs with clearly higher effect sizes than the psychotropic agents, but the psychiatric drugs were not generally less efficacious than other drugs. CONCLUSIONS: Any comparison of different outcomes in different diseases can only serve the purpose of a qualitative perspective. The increment of improvement by drug over placebo must be viewed in the context of the disease's seriousness, suffering induced, natural course, duration, outcomes, adverse events and societal values. PMID- 22297589 TI - Moderating role of the MAOA genotype in antisocial behaviour. AB - BACKGROUND: Recent studies have examined gene*environment (G*E) interactions involving the monoamine oxidase A (MAOA) gene in moderating the associations between exposure to adversity and antisocial behaviour. The present study examined a novel method for assessing interactions between a single gene and multiple risk factors related to environmental and personal adversity. AIMS: To test the hypothesis that the presence of the low-activity MAOA genotype was associated with an increased response to a series of risk factors. METHOD: Participants were 399 males from the Christchurch Health and Development Study who had complete data on: (a) MAOA promoter region variable number tandem repeat genotype; (b) antisocial behaviour (criminal offending) to age 30 and convictions to age 21; and (c) maternal smoking during pregnancy, IQ, childhood maltreatment and school failure. RESULTS: Poisson regression models were fitted to three antisocial behaviour outcomes (property/violent offending ages 15-30; and convictions ages 17-21), using measures of exposure to adverse childhood circumstances. The analyses revealed consistent evidence of G x E interactions, such that those with the low-activity MAOA variant who were exposed to adversity in childhood were significantly more likely to report offending in late adolescence and early adulthood. CONCLUSIONS: The present findings add to the evidence suggesting that there is a stable G x E interaction involving MAOA, a range of adverse environmental and personal factors, and antisocial behaviour across the life course. These analyses also demonstrate the utility of using multiple environmental/personal exposures to test G*E interactions. PMID- 22297590 TI - Short inter-pregnancy interval and schizophrenia: overestimating the risk. PMID- 22297591 TI - Care clusters and mental health Payment by Results. PMID- 22297592 TI - Care clusters and mental health Payment by Results. PMID- 22297593 TI - Care clusters and mental health Payment by Results. PMID- 22297595 TI - Childhood sexual abuse and chronic fatigue syndrome. PMID- 22297596 TI - Clozapine v. chlorpromazine in treatment-naive first-episode schizophrenia. PMID- 22297597 TI - Effect of nonsurgical periodontal therapy on crevicular fluid and serum glutathione peroxidase levels. AB - BACKGROUND: Plasma glutathione peroxidase (eGPx) is an important selenium containing antioxidant in human defense against oxidative stress. While crevicular fluid (GCF) eGPx levels and its association with periodontal disease is well documented, there is no data on correlation of GCF and serum eGPx levels in chronic periodontitis. Hence this study was undertaken to further probe into the role of oxidative stress in periodontal diseases and effect of nonsurgical periodontal therapy (NSPT) by correlating GCF and serum levels of eGPx. MATERIALS AND METHODS: Thirty subjects (16-Males and 14-Females; age: 30-38 years) participated in the study. The subjects were divided, based on gingival index, probing pocket depth and clinical attachment level into: Healthy (group-1, n=10), Gingivitis (group-2, n=10) and Periodontitis (group-3, n=10). Chronic periodontitis patients after NSPT constituted group 4. GCF and serum samples collected from each subject were quantified for eGPx levels using Enzyme linked Immunosorbent Assay. RESULTS: The mean eGPx concentrations increased from health (14.01 ng/MUl and 78.26 ng/ml) to gingivitis (22.86 ng/MUl and 90.44 ng/ml) and then to periodontitis (29.89 ng/MUl and 103.43 ng/ml), in GCF and serum respectively. After NSPT, there was statistically significant reduction in eGPx concentration in GCF and serum (19.41 ng/MUl and 85.21 ng/ml). Further, all the GCF eGPx values showed a positive correlation to that of serum eGPx level. CONCLUSION: Thus, increased eGPx concentration in GCF can be considered as an indicator of local increase in oxidative stress. While, increase in serum eGPx levels indicates that periodontal disease can also lead to increased oxidative stress at the systemic level. PMID- 22297598 TI - Apo lipoprotein A1 gene polymorphisms predict cardio-metabolic risk in South Asian immigrants. AB - OBJECTIVES: Coronary artery disease (CAD) is a leading cause of death globally with increasing burden in South Asians in the US. Specific genetic variants that influence CAD have not been fully assessed in South Asian Immigrants. The goal is to identify Apo lipoprotein A1 (APOA1) gene polymorphisms and their association with CAD risk factors, metabolic syndrome and dysfunctional HDL (Dys-HDL). METHODS: A community-based study on South Asians aged 35--65 years without CAD was conducted. APOA1 gene sequencing was performed and genotypes compared with cardiovascular findings. RESULTS: The prevalence of metabolic syndrome and dysfunctional-HDL was 29.7% and 26%, respectively. Six novel APOA1 gene single nucleotide peptides ({SNPs}) were analyzed. Three of the six SNPs (G2, G3, and G5) were found to be associated with metabolic syndrome; G2 (T655C) (p=0.044), G3 (T756C) (p=0.037) and G5 (T1001C) (p=0.037). APOA1 gene SNP G1 (T319C) was highly correlated with low HDL levels (p=0.001). In our study, both associations of APOA1 SNPs with metabolic syndrome and low HDL remained after age-adjustment. CONCLUSION: Discovery of novel gene polymorphisms will help to understand further the causes of excess CAD risk in South Asians so that preventative strategies targeted to high-risk group can be developed. PMID- 22297599 TI - Human neutrophil peptides 1-3 as gastric cancer tissue markers measured by MALDI imaging mass spectrometry: implications for infiltrated neutrophils as a tumor target. AB - OBJECTIVE: Human neutrophil peptides (HNPs) -1, -2 and -3 are significantly upregulated and were reported as biomarkers in gastric cancer (GC). However, the tissue location and function of HNPs 1-3 are still unclear in GC, and the spatial distribution of the triad needs to be disclosed. The aims of this study were to investigate the distribution and relationships among HNPs-1, -2 and -3, and assess whether infiltrated neutrophils accumulate in gastric tumor. METHODS: In this study, paired samples (n=33) of the GC tissues and adjacent normal tissues from the same patients were obtained from surgery. Expression of HNPs 1-3 were detected by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The distributions of the HNPs 1-3 in GC tissues were investigated. After verification of HNPs-1 by immunohistochemistry, infiltrated neutrophils were also detected. Then, an in vitro assay was used to observe the binding capacity and measure the cytotoxic effect of HNPs-1 against AGS cells. RESULTS: Comparing to neighboring normal tissue, expressional level of HNPs 1-3 were significantly higher and their distributions overlapped in cancerous tissues of GC patients with high abundance in the lamina propria, whereas HNPs-1 was identified as the highest major peak. Moreover, HNPs-1, -2 and -3 correlated with each other. Besides, we also observed that increased infiltrated neutrophils accumulating in GC tissues, indicating that a strong positive correlation between HNPs 1-3 and infiltrated neutrophils. In addition, the further investigated demonstrated that the major peptide, HNPs-1, was statistically increased with the advance of tumor development from the early to advanced stage of GC (p< 0.05). Moreover, we also noticed that HNPs-1 with a great binding capacity to GC AGS cells in vitro can inhibit tumor cell growth. CONCLUSIONS: Our results suggest that neutrophil secreted peptides, HNPs 1-3, increased in the GC tissues and could be used as potential biomarkers detected using MALDI-TOF MS, implying that elevated neutrophils may be used as a tumor target for tumor treatment. The binding capacity of HNPs-1 with GC cells implies that tracking molecules conjugated with HNPs-1 could be applied as a specific probe for GC diagnoses. PMID- 22297600 TI - Impact of renin-angiotensin-aldosterone system gene polymorphisms on left ventricular dysfunction in coronary artery disease patients. AB - BACKGROUND: Left ventricular dysfunction (LVD), followed by fall in cardiac output is one of the major complications in some coronary artery disease (CAD) patients. The decreased cardiac output over time leads to activation of the renin angiotensin-aldosterone system which results in vasoconstriction by influencing salt-water homeostasis. Therefore, the purpose of the present study was to explore the association of single nucleotide polymorphisms (SNPs) in angiotensin I converting enzyme; ACE (rs4340), angiotensin II type1 receptor; AT1 (rs5186) and aldosterone synthase; CYP11B2 (rs1799998) with LVD. METHODS AND RESULTS: The present study was carried out in two cohorts. The primary cohort included 308 consecutive patients with angiographically confirmed CAD and 234 healthy controls. Among CAD, 94 with compromised left ventricle ejection fraction (LVEF ? 45) were categorized as LVD. The ACE I/D, AT1 A1166C and CYP11B2 T-344C polymorphisms were determined by PCR. Our results showed that ACE I/D was significantly associated with CAD but not with LVD. However, AT1 1166C variant was significantly associated with LVD (LVEF ? 45) (p value=0.013; OR=3.69), but CYP11B2 (rs1799998) was not associated with either CAD or LVD. To validate our results, we performed a replication study in additional 200 cases with similar clinical characteristics and results again confirmed consistent findings (p value=0.020; OR=5.20). CONCLUSION: AT1 A1166C plays important role in conferring susceptibility of LVD. PMID- 22297601 TI - Prevalence of MDR1 C3435T and CYP2B6 G516T polymorphisms among HIV-1 infected South African patients. AB - Data on genetic polymorphisms associated with response to anti-HIV drugs has accumulated over the years. Information on how polymorphisms influence drug metabolism and transport to target sites is important in guiding dosage or selection of appropriate alternative therapies. This study determined the frequency of MDR1 C3435T and CYP2B6 G516T polymorphisms associated with the transport and metabolism of efavirenz and nevirapine, in a population of South African HIV infected patients. In addition, association of polymorphisms with immunologic and virologic factors was investigated. A 207bp of MDR1 exon 26 and a 161bp of CYP2B6 exon 4 were obtained from patients by polymerase chain reaction. Analysis of population-based sequences of MDR1 revealed a frequency of 89% and 11% of C and T alleles respectively (n=197; X^{2} = 0.974; p=0.324). Restriction fragment length polymorphism (RFLP) analysis of the CYP2B6 gene revealed a prevalence of 9.5% of GG, 78.4% of GT and 12.1% of TT genotype (n= 199; X^{2} = 65.204; p=0.00). There was no significant difference between immune recovery and decline in viral load (n=53), with genotype after repeated calculations of analysis of variance (ANOVA). PMID- 22297602 TI - Resistance/response molecular signature for oral tongue squamous cell carcinoma. AB - Worldwide, the incidence of oral tongue cancer is on the rise, adding to the existing burden due to prevailing low survival and high recurrence rates. This study uses high-throughput expression profiling to identify candidate markers of resistance/response in patients with oral tongue cancer. Analysis of primary and post-treatment samples (12 tumor and 8 normal) by the Affymetrix platform (HG U133 plus 2) identified 119 genes as differentially regulated in recurrent tumors. The study groups had distinct profiles, with induction of immune response and apoptotic pathways in the non-recurrent and metastatic/invasiveness pathways in the recurrent group. Validation was carried out in tissues by Quantitative Real-Time PCR (QPCR) (n=30) and immunohistochemistry (IHC) (n=35) and in saliva by QPCR (n=37). The markers, COL5A1, HBB, IGLA and TSC individually and COL5A1 and HBB in combination had the best predictive power for treatment response in the patients. A subset of markers identified (COL5A1, ABCG1, MMP1, IL8, FN1) could be detected in the saliva of patients with oral cancers with their combined sensitivity and specificity being 0.65 and 0.87 respectively. The study thus emphasizes the extreme prognostic value of exploring markers of treatment resistance that are expressed in both tissue and saliva. PMID- 22297603 TI - Iron overload and HFE gene mutations in Czech patients with chronic liver diseases. AB - The aim of the study was to identify the prevalence of HFE gene mutations in Czech patients with chronic liver diseases and the influence of the mutations on iron status. The presence of HFE gene mutations (C282Y, H63D, and S65C) analyzed by the PCR-RFLP method, presence of cirrhosis, and serum iron indices were compared among 454 patients with different chronic liver diseases (51 with chronic hepatitis B, 122 with chronic hepatitis C, 218 with alcoholic liver disease, and 63 patients with hemochromatosis). Chronic liver diseases patients other than hemochromatics did not have an increased frequency of HFE gene mutations compared to controls. Although 33.3% of patients with hepatitis B, 43% of patients with hepatitis C, and 73.2% of patients with alcoholic liver disease had elevated transferrin saturation or serum ferritin levels, the presence of HFE gene mutations was not significantly associated with iron overload in these patients. Additionally, patients with cirrhosis did not have frequencies of HFE mutations different from those without cirrhosis. This study emphasizes the importance, not only of C282Y, but also of the H63D homozygous genetic constellation in Czech hemochromatosis patients. Our findings show that increased iron indices are common in chronic liver diseases but {?it HFE} mutations do not play an important role in the pathogenesis of chronic hepatitis B, chronic hepatitis C, and alcoholic liver disease. PMID- 22297606 TI - Proximal ulna endoprosthetic replacement for bone tumours in young patients. AB - PURPOSE: The optimal reconstructive method after resection of malignant bone tumours of the proximal ulna is unknown.We report the outcome of endoprosthetic replacement in a young patient population. METHODS: This was a retrospective review of four patients[three males and one female; mean age 17.5 (range 11 31)years] who underwent limb salvage with a proximal ulnar endoprosthetic replacement following excision of malignant bone tumour. Mean follow-up was 85 (range 14-194) months. RESULTS: All patients were alive at final follow-up and reported an improvement in pain. One patient required transhumeral amputation for intralesional excision complicating a local recurrence at one month. Two patients developed fixed flexion deformities of the elbow, one of whom required radial head excision. Mean Musculoskeletal Tumour Society (MSTS)score and Toronto Extremity Salvage Score (TESS) were 27(range 25-28) and 81 (73-88), respectively. CONCLUSIONS: Custom-made proximal ulna endoprosthetic replacement following resection of malignant bone tumours in young patients provides a stable reconstruction option with satisfactory function and without apparent compromise in patient survival. PMID- 22297607 TI - Comment on Lee et al.: a comparative study of Colles' fractures in patients between 50 and 70 years of age: percutaneous K-wiring versus volar locking plating. PMID- 22297608 TI - Ritonavir-induced lipoatrophy and dyslipidaemia is reversed by the anti inflammatory drug leflunomide in a PPAR-gamma-dependent manner. AB - BACKGROUND: The complex interplay between viral infection and virus-activated inflammatory pathways with protease inhibitors (PIs) contributes to the increased risk of developing atherosclerosis and coronary artery disease in HIV-infected patients. Leflunomide is an antirheumatic drug whose administration to HIV-1 infected persons effectively decreases T-cell turnover and activation. In this study we have investigated the effects of leflunomide on dyslipidaemia and lipodistrophy induced by ritonavir in rodents. METHODS: Mice were administered ritonavir (5 mg/kg/day) alone or in combination with leflunomide (40 mg/kg/day) for 12 days. Expression of nuclear receptor and lipidogenetic genes was measured in liver and adipose tissues. RESULTS: Administration of the HIV PI ritonavir to mice increased plasma triacylglycerols, free fatty acids and cholesterol levels, and this effect was reverted by cotreatment with leflunomide. Ritonavir administration was associated with reduced epididymal fat/body weight ratio and increased liver content of triacylglycerols content. These effects were reverted by leuflunomide. Histopathology analysis shows that exposure to ritonavir causes inflammation of epididymal fat as demonstrated by dense leukocytes infiltration as well as by increased levels of proinflammatory mediators and reduced expression and activity of peroxisome proliferator-activated receptor-gamma (PPAR gamma). Leflunomide reduced epididymal fat inflammatory-metabolic alteration induced by ritonavir and restored PPAR-gamma expression in the epididymal fat. CONCLUSIONS: We have shown that the anti-inflammatory drug leflunomide protects against ritonavir-induced inflammation and dysmetabolism in adipose tissue and might be a promising strategy in the setting of HIV-infected patients at risk for HIV-induced dyslipidaemia. PMID- 22297609 TI - The crystal structure of L-arginine. AB - We report the crystal structure of L-arginine, one of the last remaining natural amino acids for which the crystal structure has never been determined; structure determination was carried out directly from powder X-ray diffraction (XRD) data, exploiting the direct-space genetic algorithm technique for structure solution followed by Rietveld refinement. PMID- 22297610 TI - The interaction between the location of lower extremity muscle fatigue and visual condition on unipedal postural stability. AB - The purpose of this study was to investigate the effects of unilateral muscle fatigue induced on the hip flexors/extensors or the ankle plantar/dorsiflexors on unipedal postural stability under different visual conditions. Twenty-four healthy young women completed 2 testing sessions 1 week apart with a randomized order assigned according to the muscles tested. During each session, one set of muscle groups was fatigued using isokinetic contractions: ankle plantar/dorsi flexors or hip flexor/extensors. Postural stability was assessed during trials of unilateral stance on a force plate before and after the fatigue protocol. 10 s into the trial, subjects were asked to close their eyes. Mean velocity, the area of the 95% confidence ellipse, and standard deviation of velocity in anteroposterior and mediolateral directions of center of pressure displacements were calculated for two periods of 5 s, immediately before and 1 s after the eyes closure. The results of the repeated measures ANOVAs showed a significant fatigue by-fatigue segment by visual condition interaction for the CoP parameters. When the vision was removed, the interaction between fatigue and fatigue segment was significant for the CoP parameters. In conclusion, fatigue in both proximal and distal musculature of the lower extremity yielded decreased postural stability during unipedal quiet standing in healthy young women. This effect was more accentuated when visual information was eliminated. Withdrawing vision following fatigue to the proximal musculature, led to a significantly greater impairment of postural stability compared to the fatigue of more distal muscles. PMID- 22297611 TI - Cross-sectional area of psoas major muscle and hip flexion strength in youth soccer players. AB - This study aimed to clarify the differences in the cross-sectional area (CSA) of the psoas major (PM) muscle and hip flexion force (HFF) of the right (dominant) side between adolescent male soccer players and age-matched non-athletes. PM CSA at L4-L5 and HFF at 1.05 rad/s were determined in 22 early (12.8-13.6 years) and 27 late (16.1-17.9 years) adolescent soccer players and 11 early (12.6-13.5 years) and 20 late (16.0-17.7 years) adolescent non-athletes. Fat-free mass (FFM) was greater in late adolescent soccer players than in late adolescent non athletes, but was similar between the two early adolescent groups. Without the effect of age, PM CSA and HFF were greater in soccer players than in non athletes. PM CSA and HFF were significantly correlated to FFM (soccer players, r = 0.860, P < 0.0001; non-athletes, r = 0.709, P < 0.0001) and PM CSA (soccer players, r = 0.760, P < 0.0001; non-athletes, r = 0.777, P < 0.0001), respectively. The difference between soccer players and non-athletes in PM CSA was still significant even when PM CSA was covaried for FFM. On the other hand, HFF covaried for PM CSA was similar between the two groups. The current results indicate that, as compared to age-matched non-athletes: (1) not only late, but also early adolescent soccer players have a greater PM CSA even when the difference in FFM was adjusted, and (2) their superiority in hip flexion force can be attributed to the difference in PM CSA. PMID- 22297612 TI - The original family revisited after 37 years: odontoma-dysphagia syndrome is most likely caused by a microduplication of chromosome 11q13.3, including the FGF3 and FGF4 genes. AB - OBJECTIVES: Fibroblast growth factors consist of receptor tyrosine kinase binding proteins involved in growth, differentiation, and regeneration of a variety of tissues of the head and neck. Their role in the development of teeth has been documented, and their presence in human odontogenic cysts and tumors has previously been investigated. Odontoma-dysphagia syndrome (OMIM 164330) is a very rare disorder characterized by clustering of teeth as compound odontoma, dysplasia and aplasia of teeth, slight craniofacial abnormalities, and dysphagia. We have followed the clinical course of the disease in a family over more than 30 years and have identified a genetic abnormality segregating with the disorder. MATERIALS AND METHODS: We evaluated clinical data from nine different family members and obtained venous blood probes for genetic studies from three family members (two affected and one unaffected). RESULTS: The present family with five patients in two generations has remained one out of only two known cases with this very rare syndrome. All those affected showed teeth dysplasia, oligodontia, and dysplasia and odontoma of the upper and lower jaw. Additional signs included dysphagia and strictures of the oesophagus. Comorbidity in one patient included aortic stenosis and coronary artery disease, requiring coronary bypasses and aortic valve replacement. Genome-wide SNP array analyses in three family members (two affected and one unaffected) revealed a microduplication of chromosome 11q13.3 spanning 355 kilobases (kb) and including two genes in full length, fibroblast growth factors 3 (FGF3) and 4 (FGF4). CONCLUSION: The microduplication identified in this family represents the most likely cause of the odontoma dysphagia syndrome and implies that the syndrome is caused by a gain of function of the FGF3 and FGF4 genes. CLINICAL RELEVANCE: Mutations of FGF receptor genes can cause craniofacial syndromes such as odontoma-dysphagia syndrome. Following this train of thought, an evaluation of FGF gene family in sporadic odontoma could be worthwhile. PMID- 22297613 TI - Reactivity for boryl(phosphino)carbenyl carbene analogues with group 14 elements (C, Si, Ge, Sb, and Pb) as a heteroatom: a theoretical study. AB - The potential energy surfaces for the chemical reactions of group 14 carbenes have been studied using density functional theory (B3LYP/LANL2DZ). Five boryl(phosphino)-based carbene (B-E-P) species, where E = C, Si, Ge, Sn, and Pb, have been chosen as model reactants in this work. Also, four kinds of chemical reactions; intramolecular 1,2-migration, water insertion, alkene cycloaddition, and intermolecular dimerization, have been used to study the chemical reactivities of these group 14 carbenes. The present theoretical investigations suggest that the relative carbenic reactivity decreases in the order C > Si > Ge > Sn > Pb. That is, the heavier the group 14 atom (E), the more stable is the boryl(phosphino)-based B-E-P species towards chemical reactions. Our theoretical findings thus demonstrate that all boryl(phosphino)-based carbenes are isolable at room temperature because they are quite inert to chemical reactions, except that they are also moisture-sensitive molecules. Furthermore, the singlet-triplet energy splitting of the B-E-P, as described in the configuration mixing model attributed to the work of Pross and Shaik, can serve as a diagnostic tool for a better understanding and predicting of their chemical reactivities, kinetically and thermodynamically. The results obtained allow a number of predictions to be made. PMID- 22297614 TI - Molecular characterization of the porcine MTPAP gene associated with meat quality traits: chromosome localization, expression distribution, and transcriptional regulation. AB - MTPAP (mitochondrial poly(A) polymerase) gene plays a role in stabilizing the level of mitochondrial mRNAs and controlling the poly(A) length of human mitochondrial mRNAs. In this study, 2,296 bp partial cDNA sequences of the porcine MTPAP gene were obtained, which contained 1,746 bp full-length coding regions flanked by a 500 bp partial 3'-UTR. The porcine MTPAP gene was assigned to SSC10q14-q16 using the radiation hybrid (IMpRH) panel and chromosome electric location methods. Q-PCR analysis showed that MTPAP was expressed in all analyzed tissues, and has higher expression in heart, liver, skeletal muscles, and fat. One single nucleotide polymorphism g.2421T>A in intron5 of MTPAP gene was identified and detected by DdeI PCR-RFLP. Association of the genotypes with economic traits showed that different genotypes were significantly associated with juiciness, individuals with genotype AT displayed a significantly higher juiciness compared to genotype TT. The C/EBPbeta transcription factors was up regulation the expression of MTPAP by analyzing a series of MTPAP promoter reporter constructs using the dual-luciferase assay system, it indicated that MTPAP gene maybe play a critical role in fat deposition regulation which is regulated by C/EBPbeta transcription factor. These findings provide an important basis for further understanding of porcine MTPAP regulation and function in swine. PMID- 22297615 TI - Curcumin causes promoter hypomethylation and increased expression of FANCF gene in SiHa cell line. AB - Curcumin and resveratrol were evaluated for their potential to cause reversal of promoter hypermethylation and associated gene expression of FANCF in SiHa cell line. Methylation specific PCR along with bisulphite sequencing revealed the demethylation of 12 CpG sites out of 15 CpG sites spanning ?280 to ?432 region of FANCF promoter after treatment with curcumin and fivefold up regulation of FANCF gene expression as shown by qRT-PCR. In vitro methylation assay also showed that M.SssI an analogue of DNMT1 was effectively inhibited at 50 lM concentration of curcumin. Resveratrol was not found to be effective in causing reversal of promoter hypermethylation of FANCF gene when used at 20 lM for 4 days in SiHa cell line. PMID- 22297616 TI - Human anti-EGFL7 recombinant full-length antibodies selected from a mammalian cell-based antibody display library. AB - Epidermal growth factor-like domain 7 (EGFL7) has been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis. The advent of antibody display technology (phage, bacteria, and yeast) led to an enormous revival in the use of antibodies as diagnostic and therapeutic tools for fighting cancer. However, problems with protein folding, posttranslational modification, and codon usage still limit the number of improved antibodies that can be obtained. We describe here the isolation of an EGFL7-specific antibody from a mammalian cell-based full-length antibody display library generated from peripheral blood mononuclear cells of patients with hepatocellular carcinoma. Using a novel vector, contained glycosylphosphatidylinositol anchor and restriction enzyme sites NheI and ClaI, antibody libraries are displayed as whole IgG molecules on the cell surface and screened for specific antigen binding by a combination of magnetic beads and measured by cell ELISA. Anti-EGFL7 antibody was successfully isolated from the library. The mammalian cell-based full-length antibody display library is a great potential application for rapid identification and cloning of human mAbs of targeting hepatocellular carcinoma. PMID- 22297617 TI - Analysis of cell cycle position in mammalian cells. AB - The regulation of cell proliferation is central to tissue morphogenesis during the development of multicellular organisms. Furthermore, loss of control of cell proliferation underlies the pathology of diseases like cancer. As such there is great need to be able to investigate cell proliferation and quantitate the proportion of cells in each phase of the cell cycle. It is also of vital importance to indistinguishably identify cells that are replicating their DNA within a larger population. Since a cell's decision to proliferate is made in the G1 phase immediately before initiating DNA synthesis and progressing through the rest of the cell cycle, detection of DNA synthesis at this stage allows for an unambiguous determination of the status of growth regulation in cell culture experiments. DNA content in cells can be readily quantitated by flow cytometry of cells stained with propidium iodide, a fluorescent DNA intercalating dye. Similarly, active DNA synthesis can be quantitated by culturing cells in the presence of radioactive thymidine, harvesting the cells, and measuring the incorporation of radioactivity into an acid insoluble fraction. We have considerable expertise with cell cycle analysis and recommend a different approach. We Investigate cell proliferation using bromodeoxyuridine/fluorodeoxyuridine (abbreviated simply as BrdU) staining that detects the incorporation of these thymine analogs into recently synthesized DNA. Labeling and staining cells with BrdU, combined with total DNA staining by propidium iodide and analysis by flow cytometry offers the most accurate measure of cells in the various stages of the cell cycle. It is our preferred method because it combines the detection of active DNA synthesis, through antibody based staining of BrdU, with total DNA content from propidium iodide. This allows for the clear separation of cells in G1 from early S phase, or late S phase from G2/M. Furthermore, this approach can be utilized to investigate the effects of many different cell stimuli and pharmacologic agents on the regulation of progression through these different cell cycle phases. In this report we describe methods for labeling and staining cultured cells, as well as their analysis by flow cytometry. We also include experimental examples of how this method can be used to measure the effects of growth inhibiting signals from cytokines such as TGF-beta1, and proliferative inhibitors such as the cyclin dependent kinase inhibitor, p27KIP1. We also include an alternate protocol that allows for the analysis of cell cycle position in a sub-population of cells within a larger culture. In this case, we demonstrate how to detect a cell cycle arrest in cells transfected with the retinoblastoma gene even when greatly outnumbered by untransfected cells in the same culture. These examples illustrate the many ways that DNA staining and flow cytometry can be utilized and adapted to investigate fundamental questions of mammalian cell cycle control. PMID- 22297618 TI - The epidemiology of finding a dead body: reports from inner-city Baltimore, Maryland US. AB - In the US, there are no national statistics on encountering a dead body, which can be viewed as a measure of community health and a stressful life event. Participants for an HIV prevention intervention targeting drug users were recruited in areas of inner-city Baltimore, Maryland. Nine hundred and fifty-one respondents, most with a history of drug use, were asked "have you ever found a dead body?" and 17.0% reported they had. Leading causes of death were: violence (37%), natural causes (22.2%), drug overdose (21.6%), accidental death (3.1%), and suicide (2.5%). In multivariate logistic models, respondents with longer history of drug use and more roles in a drug economy were more likely to be exposed to a dead body. The study results suggest that this population has a high level of experiences with mortality associated with violence and drugs. To obtain a better understanding of community health, future studies should assess not only morbidity and mortality, but also how death and illness is experienced by the community. PMID- 22297619 TI - Sortilin and SorLA regulate neuronal sorting of trophic and dementia-linked proteins. AB - Sortilin and SorLA are members of the Vps10p domain receptor family, the Sortilins, which comprise five type I transmembrane receptors differentially expressed in neuronal tissues of the central and peripheral nervous system. Since the identification of sortilin in 1997, members of this receptor family are recognized as sorting receptors primarily in the trans-Golgi network, interacting with a wide range of ligands comprising other transmembrane receptors as well as soluble proteins from neurotrophic factors to enzymes targeted for lysosomes. Specifically, the involvement of sortilin in neutrophin signaling in healthy and injured neurons is increasingly recognized, as well as the impact of SorLA on the cellular processing of amyloid precursor protein, an important component in Alzheimer's disease. The current understanding of these issues as well as the recent recognition of a molecular link between sortilin and frontotemporal dementia is addressed in this present review. PMID- 22297620 TI - An approach to combining parallel and cross-over trials with and without run-in periods using individual patient data. AB - BACKGROUND: In active run-in trials, where patients may be excluded after a run in period based on their response to the treatment, it is implicitly assumed that patients have individual treatment effects. If individual patient data are available, active run-in trials can be modelled using patient-specific random effects. With more than one trial on the same medication available, one can obtain a more precise overall treatment effect estimate. METHODS: We present a model for joint analysis of a two-sequence, four-period cross-over trial (AABB/BBAA) and a three-sequence, two-period active run-in trial (AB/AA/A), where the aim is to investigate the effect of a new treatment for patients with pain due to osteoarthritis. RESULTS: Our approach enables us to separately estimate the direct treatment effect for all patients, for the patients excluded after the active run-in trial prior to randomisation, and for the patients who completed the active run-in trial. A similar model approach can be used to analyse other types of run-in trials, but this depends on the data and type of other trials available. LIMITATIONS: We assume equality of the various carry-over effects over time. CONCLUSIONS: The proposed approach is flexible and can be modified to handle other designs. Our results should be encouraging for those responsible for planning cost-efficient clinical development programmes. PMID- 22297621 TI - Age or stage structure? A comparison of dynamic outcomes from discrete age- and stage-structured population models. AB - Discrete stage-structured density-dependent and discrete age-structured density dependent population models are considered. Regarding the former, we prove that the model at hand is permanent (i.e., that the population will neither go extinct nor exhibit explosive oscillations) and given density dependent fecundity terms we also show that species with delayed semelparous life histories tend to be more stable than species which possess precocious semelparous life histories. Moreover, our findings together with results obtained from other stage-structured models seem to illustrate a fairly general ecological principle, namely that iteroparous species are more stable than semelparous species. Our analysis of various age-structured models does not necessarily support the conclusions above. In fact, species with precocious life histories now appear to possess better stability properties than species with delayed life histories, especially in the iteroparous case. We also show that there are dynamical outcomes from semelparous age-structured models which we are not able to capture in corresponding stage structured cases. Finally, both age- and stage-structured population models may generate periodic dynamics of low period (either exact or approximate). The important prerequisite is to assume density-dependent survival probabilities. PMID- 22297622 TI - Analysis of Biochemical Equilibria Relevant to the Immune Response: Finding the Dissociation Constants. AB - This paper analyzes the biochemical equilibria between bivalent receptors, homo bifunctional ligands, monovalent inhibitors, and their complexes. Such reaction schemes arise in the immune response, where immunoglobulins (bivalent receptors) bind to pathogens or allergens. The equilibria may be described by an infinite system of algebraic equations, which accounts for complexes of arbitrary size n (n being the number of receptors present in the complex). The system can be reduced to just 3 algebraic equations for the concentrations of free (unbound) receptor, free ligand and free inhibitor. Concentrations of all other complexes can be written explicitly in terms of these variables. We analyze how concentrations of key (experimentally-measurable) quantities vary with system parameters. Such measured quantities can furnish important information about dissociation constants in the system, which are difficult to obtain by other means. We provide analytical expressions and suggest specific experiments that could be used to determine the dissociation constants. PMID- 22297623 TI - Honeycomb architecture of carbon quantum dots: a new efficient substrate to support gold for stronger SERS. AB - The rational assembly of quantum dots (QDs) in a geometrically well-defined fashion opens up the possibility of accessing the full potential of the material and allows new functions of the assembled QDs to be achieved. In this work, well confined two-dimensional (2D) and 3D carbon quantum dot (CQD) honeycomb structures have been assembled by electrodeposition of oxygen-rich functional CQDs within the interstitial voids of assemblies of SiO(2) nanospheres, followed by extraction of the SiO(2) cores with HF treatment. Although made from quantum sized carbon dots, the CQD assemblies present a solid porous framework, which can be further used as a sacrificial template for the fabrication of new nanostructures made from other functional materials. Based on the unique honeycomb architecture of the CQDs, which allows the more efficient adsorption of molecules, the formed Au nanoparticles on the CQD honeycomb exhibit 8-11 times stronger surface enhanced Raman scattering (SERS) effect than the widely used Au nanoparticle SERS substrate for the highly sensitive detection of target molecules. This work provides a new approach for the design and fabrication of ultrasensitive SERS platforms for various applications. PMID- 22297624 TI - Toluidine blue for the intraoperative staining of the ureters. Studies on the safe administration in rats. AB - PURPOSE: Acute cardiovascular events have repeatedly been reported to occur during the intraoperative presentation of the urinary tract with toluidine blue (TB). We here assessed the minimum TB dose required, and its safest and most suitable form of intravenous administration for the intraoperative staining of the ureters in rats. METHODS: TB (0.13, 0.4, 1.3, or 4.0 mg/kg) was administered to anesthetized rats either by intravenous injection within 1 min or by infusion within 10 min. During the experiments,biomonitoring parameters such as electrocardiograms (ECGs)and mean arterial blood pressure (MAP) were recorded,blood gas analysis was performed, and methemoglobin measured. Tissue injury was assessed from released plasma enzyme activities and histopathologically. The intraoperative staining of the ureters was documented photographically,and total urinary excretion and final urine/plasma TB concentrations were determined. RESULTS: Parameters of blood gas analysis, methemoglobin concentrations, and markers of tissue injury were slightly affected by the two highest TB doses but not at all by the lower ones. At doses of >=0.4 mg/kg, ureters were stained sufficiently. Staining was more intense, and urine excretion of TB higher on average when the dye was injected.The 1-min injection of >=1.3 mg TB/kg strongly and temporarily decreased the MAP, while the infusions caused lesser effects. Mean ECG parameters were not affected by any TB administration, but one animal developed a temporary bundle branch block after the 1-min injection of 4.0 mg/kg. CONCLUSIONS: In rats, intravenous injection of 0.4 mg TB/kg was sufficient for the intraoperative staining of the urinary tract without the risk of severe cardiovascular and hemodynamic side effects. Provided our results are transferable to humans, the administration of low TB doses could allow its safer clinical use for the intraoperative visualization of the ureters. PMID- 22297625 TI - Comparison of dexamethasone with ondansetron or haloperidol for prevention of patient-controlled analgesia-related postoperative nausea and vomiting: a randomized clinical trial. AB - BACKGROUND: Patient-controlled analgesia (PCA) with parenteral opioids is associated with a high incidence of postoperative nausea and vomiting (PONV). The aim of the present study was to compare the efficacy of dexamethasone plus haloperidol with dexamethasone plus ondansetron for the prevention of PCA-related PONV. Patients who received dexamethasone alone were used as controls. METHODS: A total of 135 female patients (n = 45 in each of three groups) were eligible to participate in this randomized trial. A total of 135 female patients (n = 45 in each of three groups) were eligible to participate in this randomized trial. Dexamethasone 5 mg IV was administered after the induction of anesthesia in dexamethasone group (group D) patients. Patients in the dexamethasone plus haloperidol group (group DH) and in the dexamethasone plus ondansetron (group DO) further received haloperidol 2 mg IM or ondansetron 4 mg IV, respectively, 30 min before the end of surgery. The complete response rates, incidence of PONV, need for rescue medication, average pain and sedation scores, recovery times, and adverse events were observed postoperatively. RESULTS: The incidences of total PONV in the first 24 h in groups DH (35%) and DO (30%) were significantly lower than those of group D (57%) (p < 0.05 for each comparison). The differences between groups DH and DO were insignificant. The incidence of PONV was significantly smaller in the DH and DO groups than predicted by the patients' underlying risks. Pain scores, sedation scores, and recovery times were similar among the three study groups, and no clinically relevant prolongation of the electrocardiographic QTc interval was observed in any patient. conclusions: Dexamethasone 5 mg with either haloperidol 2 mg or ondansetron 4 mg provides a better antiemetic effect than dexamethasone 5 mg alone in patients receiving postoperative morphine PCA. PMID- 22297626 TI - A mathematical model for predicting malignancy of solitary pulmonary nodules. AB - BACKGROUND: The goal of the present study was to differentiate between benign and malignant solitary pulmonary nodules (SPN) by developing a mathematical prediction model. METHODS: Records from 371 patients (197 male, 174 female) with SPN between January 2000 and September 2009 were reviewed (group A). Clinical data were collected to estimate the independent predictors of malignancy of SPN with multivariate logistic regression analysis. A clinical prediction model was subsequently developed. Between October 2009 and May 2011, data from an additional 145 patients with SPN were used to validate this new clinical prediction model (group B). The same data were also estimated with two previously published models for comparison with our new model. RESULTS: The median patient age was 57.1 years in group A; 54% of the nodules were malignant and 46% were benign. Logistic regression analysis identified six clinical characteristics (age, diameter, border, calcification, spiculation, and family history of tumor) as independent predictors of malignancy in patients with SPN. The area under the receiver operator characteristic (ROC) curve for our model (0.874 +/- 0.028) was higher than those generated using the other two reported models. In our model, sensitivity = 94.5%, specificity = 70.0%, positive predictive value = 87.8%, and negative predictive value = 84.8%). CONCLUSIONS: Age, diameter, border, calcification, spiculation, and family history of tumor were independent predictors of malignancy in patients with SPN. Our prediction model was sufficient to estimate malignancy in patients with SPN and proved to be more accurate than the two existing models. PMID- 22297627 TI - Visualization versus neuromonitoring of recurrent laryngeal nerves during thyroidectomy: what about the costs? AB - BACKGROUND: The objective of the present study was to evaluate costs for thyroidectomy performed with the aid of intraoperative neural monitoring (IONM), which has gained widespread acceptance during thyroid surgery as an adjunct to the gold standard of visual nerve identification. METHODS: Through a micro costing approach, the thyroidectomy patient-care process (with and without IONM) was analyzed by considering direct costs (staff time, consumables, equipment, drugs, operating room, and general expenses). Unit costs were collected from hospital accounting and standard tariff lists. To assess the impact of the IONM technology on hospital management, three macro-scenarios were considered: (1) traditional thyroidectomy; (2) thyroidectomy with IONM in a high-volume setting (5 procedures per week); and (3) thyroidectomy with IONM in a low-volume setting (1 procedure per week). Energy-based devices (EBD) for hemostasis and dissection in thyroidectomy were also evaluated, as well as the reimbursement made by the Italian Healthcare System on the basis of diagnosis related groups (DRGs), about ?2,600. RESULTS: Comparison between costs and the DRG fee shows an underfunding of total hospitalization costs for all thyroidectomies, regardless of IONM use (scenario 1: ?3,471). The main cost drivers are consumables and technologies (25%), operating room (16%), and staff (14%). Hospitalization costs for a thyroidectomy with IONM range from ?3,713 to ?3,770 (scenarios 2 and 3), 5-7% higher than those for traditional thyroidectomy. Major economic differences emerge when an EBD is used (?3,969). CONCLUSIONS: The regional DRG tariff for thyroid surgery is barely sufficient to cover conventional surgery costs. Intraoperative neural monitoring accounts for 5-7% of the hospitalization costs for a thyroidectomy. PMID- 22297628 TI - Distribution and source apportionment of polycyclic aromatic hydrocarbons (PAHs) in surface soils from five different locations in Klang Valley, Malaysia. AB - The concentrations of polycyclic aromatic hydrocarbons (PAHs) in soil samples were measured at five different sites within Klang Valley, Malaysia. The results showed that the total concentrations of the fourteen priority PAHs ranged from 64 to 155 MUg/kg. Irrespective of the land use, all the measured soil PAH concentrations in this study were significantly lower than that found in soil samples in temperate regions. The profile of PAHs in the soils was dominated by the LMW PAHs. The PAHs in Klang Valley soils originated from pyrogenic sources, with a combination of petroleum and biomass combustion in vehicles, industries and non-point sources. PMID- 22297629 TI - Behavior of bromobutide in paddy water and soil after application. AB - Behavior of the herbicide bromobutide, (RS)-2-bromo-N-(alpha,alpha dimethylbenzyl)-3,3-dimethylbutyramide, in paddy water and soil after application to paddy fields was investigated to evaluate the degradation to bromobutide debromo, N-(alpha,alpha-dimethylbenzyl)-3,3-dimethylbutyramide, and runoff of the herbicide. The respective maximum concentrations of bromobutide and the metabolite were 1,640-2,230 and 11.1-15.8 MUg/L in the paddy water, and 2,210 4,140 MUg/kg dry and 74-119 MUg/kg dry in the paddy soil, respectively. The runoff ratios of the applied bromobutide from the paddy fields were calculated as 28 +/- 16%. The respective mean values of the half-lives of bromobutide in the paddy water and the soil were 2.7 +/- 0.34 days and 6.9 +/- 2.6 days, respectively. PMID- 22297630 TI - Systemic antifungal therapy in critically ill patients without invasive fungal infection*. AB - OBJECTIVE: To determine the number of adult or pediatric intensive care unit patients without documented invasive fungal infection who receive systemic antifungal therapy. DESIGN: A 1-day cross-sectional cohort study. SETTING: One hundred sixty-nine intensive care units in France and Belgium. PATIENTS: All patients staying in the participating intensive care units. INTERVENTION: None. MEASUREMENT AND MAIN RESULTS: A hierarchical mixed model was used to identify center-based and patient-based determinants of systemic antifungal therapy use. Day 28 mortality was compared in patients with and without systemic antifungal therapy. Two thousand forty-seven patients were recruited. Systemic antifungal therapy was used in 154 (7.5%) patients, including 100 without and 54 with a proven invasive fungal infection. Overall, systemic antifungal therapy consisted of monotherapy of fluconazole (60%), caspofungin (24%), voriconazole (8%), or liposomal amphotericin B (5%). Independent predictors of systemic antifungal therapy included patient-related factors (severity, emergency surgery, malignancy, Candida colonization, and severe sepsis) and center-related factors (hospital with <800 beds, solid organ transplantation activity, higher annual incidence of candidemia, uncontrolled use of fluoroquinolones, and routine systemic antifungal therapy in patients with unresolved documented or undocumented sepsis). The group given systemic antifungal therapy had greater disease severity and higher rates of sepsis and organ failures. Nevertheless, crude 28-day mortality in the systemic antifungal therapy group was not significantly higher than in the group not given systemic antifungal therapy (20% vs. 19.2%; hazard ratio, 0.97 [0.61-1.52]; p = .88). CONCLUSIONS: Systemic antifungal therapy was used in 7.5% of intensive care unit patients. Two-thirds of patients given systemic antifungal therapy had no documented invasive fungal infection. Our results warrant a trial of systemic antifungal therapy in severely ill intensive care unit septic patients without documented invasive fungal infection based on their severity of illness and the presence of Candida colonization. PMID- 22297631 TI - Restricting resident work hours: the good, the bad, and the ugly. AB - OBJECTIVES: Inadequate sleep and long work hours are long-standing traditions in the medical profession, and work schedules are especially intense in resident physicians. However, it has been increasingly recognized that the extreme hours commonly worked by residents may have substantial occupational and patient safety consequences. Largely because of these concerns, new regulations related to resident work hours came into effect July 2011, in the United States. Residents in their first year of training are now restricted to a maximum shift length of 16 hrs, with residents in subsequent years restricted to a maximum of 24 hrs. The purpose of this review is to summarize the literature regarding resident work hours in the intensive care unit, focusing on the potential positive and negative impacts of work hour limits. DATA SOURCES: The authors electronically searched MEDLINE, manually searched reference lists from retrieved articles, and reviewed their own personal databases for articles relevant to resident work hour limits. METHODS AND MAIN RESULTS: To function well, humans, including physicians, require adequate sleep. Resident work hour limits will likely reduce the incidence of fatigue-related medical errors and improve resident safety and quality of life. However, a reduction in work hours may not represent the panacea for patient safety given the potential for increased errors because of discontinuity. Furthermore, there may be other substantial negative impacts, including reduced clinical exposure, erosion of professionalism, and inadequate preparation for independent practice. Costs of implementation are likely to be substantial. CONCLUSION: Currently, there is fairly limited evidence available, and a more in depth understanding of this complex topic is required to design a residency experience that will provide the next generation of physicians the best compromise between education, experience, and quality patient care. In the end, the primary goal of the postgraduate medical education system must be to ensure the creation of healthy physicians who can provide excellent clinical care in this complex interdisciplinary medical industry and who will have long fulfilling careers providing this outstanding care to their patients. PMID- 22297632 TI - Critical role of paxillin in aging of human skin. PMID- 22297633 TI - IFN-alpha enhances IL-22 receptor expression in keratinocytes: a possible role in the development of psoriasis. PMID- 22297634 TI - IL-12 and IL-23 affect photocarcinogenesis differently. AB - Induction of DNA damage by UVR is the key event in photocarcinogenesis. IL-12 and IL-23 are related heterodimeric cytokines consisting of a common p40 unit and a p35/IL-12 and a p19/IL-23 chain, respectively. Both exert immunomodulatory activities but are also found to reduce UVR-induced DNA damage presumably via induction of DNA repair. As both cytokines are also produced in the skin, they may mitigate the risk to develop UVR-induced skin cancer. This appears to be the case as mice lacking p40 were previously shown to be at higher risk for skin tumors upon chronic UVR exposure. As these mice express neither IL-12 nor IL-23, the individual effects of IL-12 or IL-23 could not be evaluated. Thus, mice lacking p35 (IL-12p35-/-) or p19 (IL-23p19-/-) were subjected to chronic UVR exposure. The Kaplan-Meier analysis indicated a significantly increased probability of tumor development in IL-23p19-/- but not in IL-12p35-/- mice. Taken together, in our model, loss of IL-23, but not of IL-12, enhances development of UVR-induced skin tumors, indicating that IL-23 but not IL-12 may counteract photocarcinogenesis. This may have impact on the development of future strategies utilizing antibodies against IL-12 and IL-23, respectively, for the treatment of inflammatory dermatoses. PMID- 22297635 TI - Hair cycle resting phase is regulated by cyclic epithelial FGF18 signaling. AB - Hair follicles repeatedly cycle through growth (anagen), regression (catagen), and resting (telogen) phases. Although the signaling molecules involved in the anagen and anagen-catagen transition have been studied extensively, the signaling that controls telogen is only partly understood. Here we show that fibroblast growth factor (Fgf)18 is expressed in a hair stem cell niche throughout telogen, and that it regulates the hair cycle through the non-growth phases. When the Fgf18 gene is conditionally knocked out in keratin 5-positive epithelial cells in mice, telogen becomes very short, giving rise to a strikingly rapid succession of hair cycles. In wild-type mice, hair follicle growth during anagen is strongly suppressed by local delivery of FGF18 protein. Our results demonstrate that epithelial FGF18 signaling and its reduction in the milieu of hair stem cells are crucial for the maintenance of resting and growth phase, respectively. PMID- 22297636 TI - A mouse model of vitiligo with focused epidermal depigmentation requires IFN gamma for autoreactive CD8+ T-cell accumulation in the skin. AB - Vitiligo is an autoimmune disease of the skin causing disfiguring patchy depigmentation of the epidermis and, less commonly, hair. Therapeutic options for vitiligo are limited, reflecting in part limited knowledge of disease pathogenesis. Existing mouse models of vitiligo consist of hair depigmentation but lack prominent epidermal involvement, which is the hallmark of human disease. They are thus unable to provide a platform to fully investigate disease mechanisms and treatment. CD8(+) T cells have been implicated in the pathogenesis of vitiligo, and expression of IFN-gamma is increased in the lesional skin of patients, however, it is currently unknown what role IFN-gamma has in disease. Here, we have developed an adoptive transfer mouse model of vitiligo using melanocyte-specific CD8(+) T cells, which recapitulates the human condition by inducing epidermal depigmentation while sparing the hair. Like active lesions in human vitiligo, histology of depigmenting skin reveals a patchy mononuclear infiltrate and single-cell infiltration of the epidermis. Depigmentation is accompanied by accumulation of autoreactive CD8(+) T cells in the skin, quantifiable loss of tyrosinase transcript, and local IFN-gamma production. Neutralization of IFN-gamma with antibody prevents CD8(+) T-cell accumulation and depigmentation, suggesting a therapeutic potential for this approach. PMID- 22297637 TI - The eumelanin intermediate 5,6-dihydroxyindole-2-carboxylic acid is a messenger in the cross-talk among epidermal cells. AB - Interest in colorless intermediates of melanocyte metabolism has traditionally been related to their role as melanin precursors, though several lines of evidence scattered in the literature suggested that these compounds may exert an antioxidant and protective function per se unrelated to pigment synthesis. Herein, we disclose the remarkable protective and differentiating effects of 5,6 dihydroxyindole-2-carboxylic acid (DHICA), a diffusible dopachrome tautomerase (DCT)-dependent eumelanin intermediate, on primary cultures of human keratinocytes. At micromolar concentrations, DHICA induced: (a) time- and dose dependent reduction of cell proliferation without concomitant toxicity; (b) enhanced expression of early (spinous keratins K1 and K10 and envelope protein involucrin) and late (loricrin and filaggrin) differentiation markers; (c) increased activities and expression of antioxidant enzymes; and (d) decreased cell damage and apoptosis following UVA exposure. The hitherto unrecognized role of DHICA as an antiproliferative, protective, and antiapoptotic endogenous cell messenger points to a reappraisal of the biological functions of melanocytes and DCT in skin homeostasis and photoprotection beyond the mere provision of melanin pigments, and provides, to our knowledge, a previously unreported possible explanation to the higher resistance of the dark-skinned eumelanic phenotypes to sunburn and skin cancer. PMID- 22297638 TI - Prognostic importance of the mitotic marker phosphohistone H3 in cutaneous nodular melanoma. AB - Mitotic count is a known prognostic predictor in cutaneous melanoma, and is included in the current American Joint Committee on Cancer tumor-node-metastasis (TNM) staging system. The mitotic marker phosphohistone H3 (PHH3) is considered to facilitate counting of mitosis, and the purpose of this study was to evaluate the prognostic significance and strength of PHH3 in comparison with standard mitotic counting in cutaneous malignant melanoma. A total of 457 consecutive cases of nodular cutaneous melanoma were initially included in this series. The mitotic count was assessed on hematoxylin and eosin sections, and PHH3 was then examined by immunohistochemistry on standard sections of paraffin-embedded tumor tissue. Both the mitotic count and the number of PHH3-stained mitotic figures were recorded in a minimum area of 1 mm(2). Increased mitotic count and PHH3 value were both associated with unfavorable features like tumor thickness and presence of ulceration. Univariate survival analysis showed a highly significant prognostic impact of mitotic count and PHH3, whereas multivariate analysis indicated PHH3 to be a stronger prognostic indicator than mitotic count. Assessment of mitotic activity by PHH3 immunostaining might have important practical advantages, and should be further studied to consider a place in routine examination of all cutaneous melanomas. PMID- 22297639 TI - Identification of quantitative trait loci in experimental epidermolysis bullosa acquisita. AB - Epidermolysis bullosa acquisita (EBA) is a chronic mucocutaneous autoimmune skin blistering disease. Several lines of evidence underscore the contribution of autoantibodies against type VII collagen (COL7) to the pathogenesis of EBA. Furthermore, EBA susceptibility is associated with the MHC haplotype in patients (HLA-DR2) and in immunization-induced EBA in mice (H2s). The latter study indicated an additional contribution of non-MHC genes to disease susceptibility. To identify non-MHC genes controlling EBA susceptibility, we intercrossed EBA susceptible MRL/MpJ with EBA-resistant NZM2410/J and BXD2/TyJ as well as Cast mice. Mice of the fourth generation of this four-way autoimmune-prone advanced intercross line were immunized with a fragment of murine COL7 to induce EBA. Anti COL7 autoantibodies were detected in 84% of mice, whereas deposition of complement at the dermal-epidermal junction (DEJ) was observed in 50% of the animals; 33% of immunized mice presented with overt clinical EBA. Onset of clinical disease was associated with several quantitative trait loci (QTLs) located on chromosomes 9, 12, 14, and 19, whereas maximum disease severity was linked to QTLs on chromosomes 1, 15, and 19. This more detailed insight into the pathogenesis of EBA may eventually lead to new treatment strategies for EBA and other autoantibody-mediated diseases. PMID- 22297640 TI - Low herpesvirus entry mediator (HVEM) expression on dermal fibroblasts contributes to a Th2-dominant microenvironment in advanced cutaneous T-cell lymphoma. AB - LIGHT (lymphotoxin-like, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for herpesvirus entry mediator (HVEM), a receptor expressed by T lymphocytes) is a ligand for HVEM. LIGHT-HVEM interactions are important in T helper type 1 (Th1) immune responses. In some cases with early stages of cutaneous T cell lymphoma (CTCL), IL-2, IFN-gamma, and Th1 chemokines are expressed in lesional skin, while IL-4, IL-5, and Th2 chemokines are dominant in advanced CTCL. In this study, we investigated roles of LIGHT and HVEM in the microenvironment of CTCL. LIGHT enhanced production of Th1 chemokines, such as CXC chemokine ligand (CXCL) 9, CXCL10, and CXCL11, from IFN-gamma-treated dermal fibroblasts via phosphorylation of inhibitor kappaBalpha. Messenger RNA levels of these chemokines were increased in lesional skin of early CTCL. Interestingly, while LIGHT expression in CTCL skin correlated with disease progression, HVEM expression was significantly decreased in advanced CTCL skin. HVEM was detected in dermal fibroblasts in early CTCL skin, but not in advanced CTCL skin in situ. These results suggest that low HVEM expression on dermal fibroblasts in advanced CTCL skin attenuates expression of Th1 chemokines, which may contribute to a shift to a Th2-dominant microenvironment as disease progresses. PMID- 22297641 TI - Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials. PMID- 22297642 TI - Application of an indoleamine 2,3-dioxygenase-expressing skin substitute improves scar formation in a fibrotic animal model. PMID- 22297643 TI - Hydroa vacciniforme is associated with increased numbers of Epstein-Barr virus infected gammadeltaT cells. AB - Hydroa vacciniforme (HV) is a rare photosensitivity disorder of childhood associated with Epstein-Barr virus (EBV)(+) T-cell infiltration. We have summarized clinical manifestations of HV, and analyzed EBV(+) T-cell subsets as well as EBV DNA load in lymphocyte fractions, in comparison with hypersensitivity to mosquito bites (HMB), an EBV-associated T/natural killer (NK) lymphoproliferative disorder. We found that 31 of 33 (93.9%) HV lesions were composed of EBV(+) T cells and reactive EBV(-) cytotoxic T cells, without significant CD56(+) cell infiltration, whereas many CD56(+) cells were present in 8 of 9 (88.9%) HMB lesions. Of 13 (20.6%) HMB patients with or without HV, 12 (92.3%) showed increased percentages (>32%) of NK cells in the peripheral blood, whereas in the 16 patients with HV alone, 14 (87.5%) showed no increase. Of the 11 HV patients, 10 (90.9%) had increased percentages (>5%) of circulating gammadeltaT cells, with a mean value of 15.7 +/- 2.9%, and the gammadeltaT-cell fractions contained larger amounts of EBV DNA than non-gammadeltaT-cell fractions. A triple-labeling method revealed that all three HV patients examined had increased percentages of EBER(+), T-cell receptor (TCR)gammadelta(+), and TCRalphabeta(-) cells. Our observations indicate that HV is associated with increased numbers of EBV(+) gammadeltaT cells, whereas HMB is associated with EBV(+) NK cells. PMID- 22297644 TI - Value of diagnostic tests to predict conversion to Alzheimer's disease in young and old patients with amnestic mild cognitive impairment. AB - Using the database of the Alzheimer's Disease Neuroimaging Initiative, we examined the value of neuropsychological assessment, structural magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) biomarkers, and FDG-PET scanning with respect to prediction of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). We tested the hypothesis that CSF biomarkers and FDG-PET would lose prognostic value when applied in patients older than 75 years, whereas MRI and neuropsychological testing would not. At baseline 175 patients had MCI, mostly amnestic. They were followed during a mean of 2.7 years, and 81 patients converted to AD after a mean of 1.6 years. Logistic regression analyses showed that neuropsychological assessment and MRI variables predicted conversion with 63 to 67% classification success both in patients younger and older than 75 years, while CSF biomarkers attained this success rate only in patients younger than 75 years. For FDG-PET, this rate was 57% in the total sample. We conclude that the diagnostic yield of different techniques in predicting conversion from MCI to AD is moderate, and that it is affected by age of the subject under study. MRI and neuropsychological assessment remain informative in patients older than 75 years, unlike CSF biomarkers. PMID- 22297645 TI - Sulcal span in Azheimer's disease, amnestic mild cognitive impairment, and healthy controls. AB - Differences of cortical morphology between healthy controls (HC), amnestic mild cognitive impairment (MCI), and Alzheimer's disease (AD) have been repeatedly investigated using voxel-based morphometry (VBM). However, the results obtained using mainly VBM remain difficult to interpret as they can be explained by various mechanisms. The aim of the present study was to evaluate the differences of cortical morphology between HC, MCI, and AD patients using a new post processing method based on reconstruction and identification of cortical sulci. Thirty HC, 33 MCI, and 30 AD patients were randomly selected from the ADNI database. For each subject, cortical sulci were reconstructed and automatically identified using Brainvisa software. Depth and fold opening of nine large sulci were compared between HC, MCI, and AD patients. Fold opening of parietaloccipital fissure and intraparietal sulcus on both sides strongly differed between the 3 groups, with gradual increase from HC to MCI of about 1 mm and from MCI to AD of about 2 mm (right intraparietal: p = 0.005; left intraparietal: p = 0.004; right parietaloccipital: p = 0.003; left parietaloccipital: p = 0.0009). Results were left unchanged after adjustment for age, gender, and level of education. These variables were also strongly linked to neuropsychological scores, independent of age, gender, and level of education. In the present study, we found important regional differences of cortical morphology with gradual deterioration from HC to MCI to AD. The most important differences were found in parietaloccipital fissure and intraparietal sulcus. Further studies are needed to understand the involved underlying mechanisms. PMID- 22297646 TI - Dysfunctional pro-ceramide, ER stress, and insulin/IGF signaling networks with progression of Alzheimer's disease. AB - In Alzheimer's disease (AD), brain insulin and insulin-like growth factor (IGF) resistance and deficiency begin early, and worsen with severity of disease. The factors mediating progression of brain insulin/IGF resistance in AD are not well understood. We hypothesize that AD progression is mediated via negative cross talk that promotes toxic ceramide generation and endoplasmic reticulum (ER) stress. The rationale is that insulin resistance dysregulates lipid metabolism and promotes ceramide accumulation, and thereby increases inflammation and stress. Consequences include disruption of cytoskeletal function and AbetaPP Abeta secretion. The present study correlates AD stage with activation of pro ceramide genes, ceramide levels, and molecular indices of ER stress in postmortem human brain tissue. The results demonstrated that in AD, brain insulin/IGF resistance was associated with constitutive activation of multiple pro-ceramide genes, increased ceramide levels, and increased expression of pro-ER stress pathway genes and proteins. Expression of several pro-ceramide and pro-apoptotic ER stress pathway molecules increased with AD severity and brain insulin/IGF resistance. In contrast, ER stress molecules that help maintain homeostasis with respect to unfolded protein responses were mainly upregulated in the intermediate rather than late stage of AD. These findings support our hypothesis that in AD, a triangulated mal-signaling network initiated by brain insulin/IGF resistance is propagated by the dysregulation of ceramide and ER stress homeostasis, which themselves promote insulin resistance. Therefore, once established, this reverberating loop must be targeted using multi-pronged approaches to disrupt the AD neurodegeneration cascade. PMID- 22297647 TI - Anti-amyloidogenic effect of thiacremonone through anti-inflamation in vitro and in vivo models. AB - Neuroinflammation is implicated for amyloidogenesis. Sulfur compounds extracted from garlic have been shown to have anti-inflammatory properties. Previously, we have investigated that thiacremonone, a sulfur compound isolated from garlic has anti-inflammatory effects. To investigate thiacremonone's potential effect on anti-neuroinflammation and anti-amyloidogenesis, 4 week old ICR mice were given different doses of thiacremonone (1, 3, and 10 mg/kg) in drinking water for 1 month and received intraperitoneal injection of lipopolysaccharide (LPS) (250 MUg/kg/day) at last 7 days of treatment. Our data show thiacremonone decreased LPS-induced memory impairment, glial activation, pro-inflammatory mediators' expression, and amyloidogenesis. In an in vitro study, we obtained similar results, with thiacremonone (1, 2, and 5 MUg/ml) effectively decreased LPS (1 MUg/ml)-induced glial activation and inflammatory mediators generation which are implicated in amyloidogenesis. Our data also demonstrated that thiacremonone inhibited LPS-induced amyloidogenesis in cultured astrocytes and microglial BV-2 cells. NF-kappaB, a critical transcriptional factor regulating not only inflammation but also amyloid-beta generation, was inhibited by thiacremonone via blocking of phosphorylation of IkappaBalpha in mice brain as well as cultured astrocytes and microglial BV-2 cells. These results indicated that the anti inflammatory compound, thiacremonone, inhibited neuroinflammation and amyloidogenesis through inhibition of NF-kappaB activity, and thus could be applied for intervention of inflammation-related neurodegenerative disease including Alzheimer's disease. PMID- 22297650 TI - Does decline of lung function in wheezy infants justify the early start of controller medications? AB - OBJECTIVE: To compare lung function in wheezy infants, with risk factors of asthma and with some immunological parameters which may be useful as predictors of subsequent asthma. METHODS: The data of 241 infants aged 5-36 mo, with recurrent wheeze (>=3 episodes of physician confirmed wheeze) prior to receiving inhaled corticosteroids or anti-leukotrine agents was retrospectively analyzed. They were subdivided into 2 subgroups; those with asthma risk factors (132 patients) and those without (109 patients) Also, 67 healthy, age and sex matched children without recurrent wheezes were taken as control group. Total serum IgE, eosinophilic percentage, tPTEF/tE (time to peak expiratory flow to total expiratory time), total respiratory system compliance (Crs) and resistance of the respiratory system (Rrs) was done for patients and control groups. RESULTS: Wheezy infants had a significantly higher eosinophilic percentage and total serum IgE as well as a significantly lower pulmonary function parameters when compared to healthy controls. Wheezy infants with positive family history of asthma and those who had not been breast fed showed significant reduction in the mean values of tPTEF/tE and increased both eosinophilic percentage and total serum IgE. Crs was significantly decreased in wheezy infants with positive seasonal variations and those who had increased both eosinophilic percentage and total serum IgE. Rrs showed significant increase in wheezy infants with positive family history of atopy and those who had increased eosinophilic percentage and increased total serum IgE. CONCLUSIONS: Lung function, eosinophilic percentage, total serum IgE and asthma risk factors could be used as predictors for ongoing wheeze in this subset of children. PMID- 22297651 TI - The impact of endoscopic retrograde cholangiopancreatography education on radiation exposure to experienced endoscopist: 'trainee effect'. AB - BACKGROUND: Endoscopic retrograde cholangiopancreatography(ERCP), as with other fluoroscopic procedures, carries the risk of exposure of staff to radiation. However, over the last two decades, only a few studies have investigated this risk. OBJECTIVE: The aim of this work was to evaluate the dose of radiation exposure to staff participating in ERCP procedures in a busy teaching hospital that performs more than 1,850 procedures annually. METHODS: The entire ERCP staff consisted of the experienced endoscopist, the assistant, and two nurses who were responsible for monitoring patients as well as keeping their heads in position during the procedure. RAD DOSE NEB.226 dosimeters, which were provided by the Turkish Atomic Energy Authority, were used for this study. RESULTS: Data on 110 consecutive therapeutic ERCP procedures was recorded. The mean fluoroscopy time was 5.65 +/- 4.71 min. The mean fluoroscopy time of the 61 procedures performed by an experienced endoscopist alone was 5.41 +/- 4.65 min, whereas the mean fluoroscopy time for the 49 procedures during which an assistant was involved was 5.94 +/- 4.81 min (p = 0.56). In terms of median dose of ionizing radiation exposure to the eyes, the dose measurement per procedure in which the primary endoscopist participated alone was 72 microsievert (MUSv), compared to 92 MUSv when an assistant took part in theproceedings. Considering that the recommended annual equivalent dose limit to the lens of the eye is 150 mSv, by performing 1,850 procedures annually, the primary endoscopist exceeds this limit. CONCLUSIONS: Based on our results, taking into consideration the heavy workload in our hospital, it would seem that more experienced endoscopists are required to help provide training in ERCP, and that the use of lead acrylic goggles is required to decrease radiation exposure to the eyes. PMID- 22297652 TI - Lactulose hydrogen breath test and functional symptoms in pediatric patients. AB - BACKGROUND: The role of small intestinal bacterial overgrowth (SIBO) in functional digestive disorders in the pediatric population is a matter of controversy, since methods currently used to establish this diagnosis are difficult to interpret. The aim of this work was to analyze the characteristics of the lactulose H(2) breath test (LHBT) in children with functional gastrointestinal symptoms according to more recent criteria. METHODS: Seventy-two patients and 17 controls were enrolled. A questionnaire was administered regarding digestive symptoms (abdominal pain, bloating, vomiting, and bowel movement disorders). A lactose hydrogen breath test was performed to rule out lactose malabsorption and a LHBT was used to measure the time elapsed between lactulose oral ingestion and an increment of H(2) concentration of 20 ppm over basal. RESULTS: There were no differences of age and gender between patients and controls. Mean time to 20-ppm change was shorter in patients (56.3 +/- 3 min) compared to healthy children (74.7 +/- 5 min), p?0.05. In 39% of patients, rise of H(2) occurred during the first 40 min after lactulose ingestion, and in almost all controls, an increment was observed between 50 and 90 min (p?0.05). Symptoms were unrelated to time to 20-ppm change. CONCLUSIONS: An abnormal LHBT was found in children with functional symptoms of the digestive tract, but the exact mechanism involved, accelerated intestinal transit or SIBO, needs to be confirmed by an additional method. PMID- 22297653 TI - Plasma ghrelin levels in patients with familial Mediterranean fever. AB - BACKGROUND: Familial Mediterranean fever (FMF) is an auto-inflammatory disorder characterized by febrile attacks. Increased acute-phase reactants are characteristic during febrile attacks. Ghrelin is a natural G-protein that decreases secretion of pro-inflammatory cytokines and acts as anti-inflammatory agent. The aim of this study was to investigate whether there is any change in ghrelin levels and whether increases in ghrelin levels can be used as a marker in these patients. SUBJECTS AND METHODS: Thirty-seven male patients and 30 healthy men as a control group were included in the study. Blood samples were obtained for ghrelin measurements both before the attacks (pre-attack period; ghrelin 1 group) and during the attacks (ghrelin 2 group). Samples were kept at -80 degrees C until the analysis was conducted and plasma ghrelin levels were measured using an immune-sorbent assay method. RESULTS: Mean ghrelin levels measured during the attacks were significantly higher (11.01 +/- 4.78 pg/ml) as compared to pre attack levels (5.78 +/- 2.17 pg/ml; p < 0.001). Similarly, mean ghrelin levels measured in FMF patients during an attack were significantly different from that of the control group (6.57 +/- 4.13 pg/ml; p < 0.001). CONCLUSIONS: In this study, high ghrelin levels were measured during attacks in FMF patients. This finding is in line with previous results regarding the fact that inflammatory response arising during an FMF attack is an acute inflammatory event. Our findings suggest that ghrelin levels measured during FMF attacks could be used as a biochemical indicator for the FMF attack in FMF patients and that it could be used for support of the diagnosis of the disease. PMID- 22297654 TI - The magnetic assembly of polymer colloids in a ferrofluid and its display applications. AB - Nonmagnetic polymer colloids have been assembled into colloidal photonic crystals in a ferrofluid by applying an external magnetic field based on the dipole-dipole interactions of "magnetic holes". The photonic crystal disassembles immediately when the magnetic field is removed. The mechanism of assembly can be explained by two simultaneous processes: phase separation and colloidal assembly. In this work, increasing the size of the building blocks still produces colorful photonic crystals due to their 2nd order diffraction. With a larger building block, the magnetic response between the polymer colloids is greatly enhanced so that an instant and reversible assembly/disassembly can be realized in a much weaker magnetic field and lower ferrofluid concentration. Based on these investigations, a magnetically controlled photonic display unit has been fabricated, which works in a weak magnetic field, has stable reflection signals and possesses fast and reversible on/off switching of reflections. PMID- 22297655 TI - Alternative detox. AB - BACKGROUND: The concept that alternative therapies can eliminate toxins and toxicants from the body, i.e. 'alternative detox' (AD) is popular. SOURCES OF DATA: Selected textbooks and articles on the subject of AD. AREAS OF AGREEMENT: The principles of AD make no sense from a scientific perspective and there is no clinical evidence to support them. AREAS OF CONTROVERSY: The promotion of AD treatments provides income for some entrepreneurs but has the potential to cause harm to patients and consumers. GROWING POINTS: In alternative medicine, simplistic but incorrect concepts such as AD abound. AREAS TIMELY FOR RESEARCH: All therapeutic claims should be scientifically tested before being advertised and AD cannot be an exception. PMID- 22297656 TI - Regulation of voltage-gated sodium current by endogenous Src family kinases in cochlear spiral ganglion neurons in culture. AB - Voltage-gated sodium (Na+) and potassium (K+)channels have been found to be regulated by Src family kinases(SFKs).However, how these channels are regulated by SFKs in cochlear spiral ganglion neurons (SGNs) remains unknown.Here, we report that altering the activity of endogenous SFKs modulated voltage-gated Na+, but not K+, currents recorded in embryonic SGNs in culture. Voltage-gated Na+ current was suppressed by inhibition of endogenous SFKs or just Src and potentiated by the activation of these enzymes. Detailed investigations showed that under basal conditions, SFK inhibitor application did not significantly affect the voltage-dependent activation, but shifted the steady-state inactivation curves of Na+ currents and delayed the recovery of Na+ currents from inactivation. Application of Src specific inhibitor, Src40-58,not only shifted the inactivation curve but also delayed the recovery of Na+ currents and moved the voltage-dependent activation curve towards the left. The pre-inhibition of SFKs occluded all the effects induced by Src40-58 application, except the left shift of the activation curve. The activation of SFKs did not change either steady-state inactivation or recovery of Na+ currents, but caused the left shift of the activation curve.SFK inhibitor application effectively prevented all the effects induced by SFK activation, suggesting that both the voltage-dependent activation and steady-state inactivation of Na+ current are subjects of SFK regulation. The different effects induced by activation versus inhibition of SFKs implied that under basal conditions, endogenously active and inactive SFKs might be differentially involved in the regulation of voltage-gated Na+ channels in SGNs. PMID- 22297657 TI - Pure spin current generation in monolayer graphene by quantum pumping. AB - We study a method to generate pure spin current in monolayer graphene over a wide range of Fermi energy by adiabatic quantum pumping. The device consists of three gate electrodes and two ferromagnetic strips, which induce a spin-splitting in the graphene through the proximity effect. A pure spin current is generated by applying two periodic oscillating gate voltages. We find that the pumped pure spin current is a sensitive oscillatory function of the Fermi energy. Large spin currents can be found at Fermi energies where there are Fabry-Perot resonances in the barriers. Furthermore, we analyze the effects of the parameters of the system on the pumped currents. Our predicted pumped spin current can be of the order of 100 nA which is measurable using the current technology. The proposed method is useful in the realization of graphene spintronic devices. PMID- 22297659 TI - Twins in polyhedral 26-facet Cu7S4 cages: synthesis, characterization and their enhancing photochemical activities. AB - Unusual polyhedral 26-facet Cu(7)S(4) cages wholly exposed with amazingly unique nanotwinned structures as building blocks were successfully synthesized via a facile ethanol-assisted sacrificial Cu(2)O templates approach. Furthermore, a solvent-controlled fabrication of polyhedral copper sulfides (Cu(7)S(4) and CuS) with different stoichiometries and microstructures can be artificially achieved, which is determined by the intrinsic difference of the surface states of Cu(2)O templates. Structural and morphological evolutions were investigated by X-ray diffraction (XRD), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM) and field-emission scanning electron microscopy (FESEM). Stoichiometric-dependent characteristics were demonstrated in the UV-vis absorption investigations. The as-prepared Cu(7)S(4) microcages exhibit higher photocatalytic activity for enhancing degradation of methylene blue, which might be attributed to their special nanotwinned building blocks. This study is of great importance in "bottom-up" assembly of unusual ordering hollow copper sulfides superstructures, but also offers a good opportunity to understand the fundamental significance of nanotwinned structures for their potential applications. PMID- 22297658 TI - Current strategies and future perspectives for intraperitoneal adhesion prevention. AB - INTRODUCTION: The formation of peritoneal adhesions still is a relevant clinical problem after abdominal surgery. Until today, the most important clinical strategies for adhesion prevention are accurate surgical technique and the physical separation of traumatized serosal areas. Despite a variety of barriers which are available in clinical use, the optimal material has not yet been found. DISCUSSION: Mesothelial cells play a crucial physiological role in friction less gliding of the serosa and the maintenance of anantiadhesive surface. The formation of postoperative adhesions results from a cascade of events and is regulated by various cellular and humoral factors. Therefore, optimization or functionalization of barrier materials by developments interacting with this cascade on a structural or pharmacological level could give an innovative input for future strategies in peritoneal adhesion prevention. For this purpose, the proper understanding of the formal pathogenesis of adhesion formation is essential. Based on the physiology of the serosa and the pathophysiology of adhesion formation, the available barriers in current clinical practice as well as new innovations are discussed in the present review. PMID- 22297660 TI - The behavioural profile of children with attention-deficit/ hyperactivity disorder and of their siblings. AB - The behavioural profiles in N = 69 index children with attention deficit/hyperactivity disorder (ADHD),N = 32 siblings with ADHD, N = 35 siblings without ADHD, and N = 36 normal controls were compared by the use of standardized parent and teacher rating scales. The four groups were matched by age and IQ. The behavioural profiles of the two ADHD groups were very similar not only in the behavioural domains of ADHD, but also in scales measuring emotional and conduct problems. Siblings without ADHD shared more similarities with normal controls except for more emotional problems. These general trends were stronger in the parent compared to the teacher ratings. These findings indicate that not only ADHD-related but also other behaviours show a strong family aggregation. The informant differences may reflect context dependent differences in child behaviour and contrast effects particularly in parental ratings. PMID- 22297661 TI - Abnormal response to emotional stimulus in male adolescents with violent behavior in China. AB - The objective of the study is to explore the characteristics of emotional stimulus in adolescents with violent behavior and to identify the correlated dysfunctional regions of the brain. An event-related functional magnetic resonance imaging was obtained while the participants passively viewed pictures with neutral or negative affective valence. 15 male adolescents with violent behavior, ranging in age from 12 to 18 years old, and 16 healthy age-matched control subjects were enrolled in the study. While looking at neutral pictures, several brain regions were activated more intensely in the violent group than the control one. After digitally subtracting the control group, these areas included the bilateral amygdala, left orbital gyrus, bilateral fusiform gyrus, and left visual cortex. While passively viewing negative pictures, the right inferior frontal gyrus and the middle frontal gyrus were less activated in the violent group than the control group. Male adolescents with violent behaviors have some dysfunctions during the processing and evaluation of information from external emotional stimulus. These individuals are inclined to interpret neutral information as threatening stimulus. PMID- 22297662 TI - Asymmetric addition of arylboronic acids to glyoxylate catalyzed by a ruthenium/Me-BIPAM complex. AB - The enantioselective synthesis of alpha-hydroxy esters by ruthenium-catalyzed 1,2 addition of arylboronic acids to tert-butyl glyoxylate is described. The use of RuCl(2)(PPh(3))(3) with (R,R)-Me-BIPAM gave optically active mandelic acids of up to 99% ee. Addition of a fluoride salt such as potassium fluoride (KF) or caesium fluoride (CsF) was effective for achieving high enantioselectivities. PMID- 22297663 TI - Synthesis of 5-alkylated barbituric acids and 3-alkylated indoles via microwave assisted three-component reactions in solvent-free conditions using Hantzsch 1,4 dihydropyridines as reducing agents. AB - Reaction of barbituric acids with aldehydes and dihydropyridines in one pot under microwave (MW) irradiation in the absence of solvent, affords 55-82% of the 5 benzylated barbituric acids. Use of alkyl nitriles or barbituric acids with indole-3-aldehyde and dihydropyridine (DHP) afforded 3-alkylated indoles in 57-76 % yield. In each case DHPs are converted to pyridines. PMID- 22297664 TI - Primary MALT lymphoma of the urinary bladder in the background of interstitial cystitis. PMID- 22297665 TI - Femoral arterial and venous catheterization for blood sampling, drug administration and conscious blood pressure and heart rate measurements. AB - In multiple fields of study, access to the circulatory system in laboratory studies is necessary. Pharmacological studies in rats using chronically implanted catheters permit a researcher to effectively and humanely administer substances, perform repeated blood sampling and assists in conscious direct measurements of blood pressure and heart rate. Once the catheter is implanted long-term sampling is possible. Patency and catheter life depends on multiple factors including the lock solution used, flushing regimen and catheter material. This video will demonstrate the methodology of femoral artery and venous catheterization of the rat. In addition the video will demonstrate the use of the femoral venous and arterial catheters for blood sampling, drug administration and use of the arterial catheter in taking measurements of blood pressure and heart rate in a conscious freely-moving rat. A tether and harness attached to a swivel system will allow the animal to be housed and have samples taken by the researcher with minimal disruption to the animal. To maintain patency of the catheter, careful daily maintenance of the catheter is required using lock solution (100 U/ml heparinized saline), machine-ground blunt tip syringe needles and the use of syringe filters to minimize potential contamination. With careful aseptic surgical techniques, proper catheter materials and careful catheter maintenance techniques, it is possible to sustain patent catheters and healthy animals for long periods of time (several weeks). PMID- 22297666 TI - Dyslipidemia: a prospective controlled randomized trial of intensive glycemic control in sepsis. AB - PURPOSE: Metabolic disturbances are quite common in critically ill patients. Glycemic control appears to be an important adjuvant therapy in such patients. In addition, disorders of lipid metabolism are associated with worse prognoses. The purpose of this study was to investigate the effects that two different glycemic control protocols have on lipid profile and metabolism. METHODS: We evaluated 63 patients hospitalized for severe sepsis or septic shock, over the first 72 h of intensive care. Patients were randomly allocated to receive conservative glycemic control (target range 140-180 mg/dl) or intensive glycemic control (target range 80-110 mg/dl). Serum levels of lowdensity lipoprotein, high-density lipoprotein, triglycerides, total cholesterol, free fatty acids, and oxidized low-density lipoprotein were determined. RESULTS: In both groups, serum levels of low-density lipoprotein, high-density lipoprotein, and total cholesterol were below normal, whereas those of free fatty acids, triglycerides, and oxidized lowdensity lipoprotein were above normal. At 4 h after admission, free fatty acid levels were higher in the conservative group than in the intensive group, progressively decreasing in both groups until hour 48 and continuing to decrease until hour 72 only in the intensive group. Oxidized low-density lipoprotein levels were elevated in both groups throughout the study period. CONCLUSIONS: Free fatty acids respond to intensive glycemic control and, because of their high toxicity, can be a therapeutic target in patients with sepsis. PMID- 22297667 TI - Validation of the Better Care(r) system to detect ineffective efforts during expiration in mechanically ventilated patients: a pilot study. AB - PURPOSE: Ineffective respiratory efforts during expiration (IEE) are a problem during mechanical ventilation (MV). The goal of this study is to validate mathematical algorithms that automatically detect IEE in a computerized (Better Care(r)) system that obtains and processes data from intensive care unit (ICU) ventilators in real time. METHODS: The Better Care(r) system, integrated with ICU health information systems, synchronizes and processes data from bedside technology. Algorithms were developed to analyze airflow waveforms during expiration to determine IEE. Data from 2,608,800 breaths from eight patients were recorded. From these breaths 1,024 were randomly selected. Five experts independently analyzed the selected breaths and classified them as IEE or not IEE. Better Care(r) evaluated the same 1,024 breaths and assigned a score to each one. The IEE score cutoff point was determined based on the experts' analysis. The IEE algorithm was subsequently validated using the electrical activity of the diaphragm (EAdi) signal to analyze 9,600 breaths in eight additional patients. RESULTS: Optimal sensitivity and specificity were achieved by setting the cutoff point for IEE by Better Care(r) at 42%. A score >42% was classified as an IEE with 91.5% sensitivity, 91.7% specificity, 80.3% positive predictive value (PPV), 96.7% negative predictive value (NPV), and 79.7% Kappa index [confidence interval (CI) (95%) = (75.6%; 83.8%)]. Compared with the EAdi, the IEE algorithm had 65.2% sensitivity, 99.3% specificity, 90.8% PPV, 96.5% NPV, and 73.9% Kappa index [CI (95%) = (71.3%; 76.3%)]. CONCLUSIONS: In this pilot, Better Care(r) classified breaths as IEE in close agreement with experts and the EAdi signal. PMID- 22297668 TI - Ineffective efforts during mechanical ventilation: the brain wants, the machine declines. PMID- 22297669 TI - Pros and cons for C4d as a biomarker. AB - The introduction of C4d in daily clinical practice in the late nineties aroused an ever-increasing interest in the role of antibody-mediated mechanisms in allograft rejection. As a marker of classical complement activation, C4d made it possible to visualize the direct link between anti-donor antibodies and tissue injury at sites of antibody binding in a graft. With the expanding use of C4d worldwide several limitations of C4d were identified. For instance, in ABO incompatible transplantations C4d is present in the majority of grafts but this seems to point at 'graft accommodation' rather than antibody-mediated rejection. C4d is now increasingly recognized as a potential biomarker in other fields where antibodies can cause tissue damage, such as systemic autoimmune diseases and pregnancy. In all these fields, C4d holds promise to detect patients at risk for the consequences of antibody-mediated disease. Moreover, the emergence of new therapeutics that block complement activation makes C4d a marker with potential to identify patients who may possibly benefit from these drugs. This review provides an overview of the past, present, and future perspectives of C4d as a biomarker, focusing on its use in solid organ transplantation and discussing its possible new roles in autoimmunity and pregnancy. PMID- 22297670 TI - MDM2 (murine double minute-2) links inflammation and tubular cell healing during acute kidney injury in mice. AB - Murine double minute (MDM)-2, an E3 ubiquitin ligase, promotes cancer cell survival and growth, by degrading the cell cycle regulator p53. Antagonism of MDM2 by the small-molecule cis-imidazoline nutlin analogs is under current study for cancer therapy. To test whether MDM2 also promotes regenerative cell growth, we determined the effects of nutlin-3a on tubule cell healing during postischemic acute kidney injury (AKI). Treatment with nutlin-3a impaired tubular cell regeneration during postischemic AKI in wild-type mice in a p53-dependent manner; however, MDM2 blockade also prevented tubular necrosis by suppressing sterile inflammation during the early postischemic phase. This effect also occurred in p53 knockout mice, indicating a second, proinflammatory, p53-independent role for MDM2 in AKI. In vitro experiments confirmed that MDM2 is required to induce mRNA expression and secretion of NFkappaB-dependent cytokines upon Toll-like receptor stimulation by enhanced binding of NFkappaB to cytokine promoter-binding sites. Thus, MDM2 links inflammation and epithelial healing during AKI. These additional biological functions need to be regarded when considering MDM2 inhibition therapy. PMID- 22297671 TI - The diurnal variation in urine acidification differs between normal individuals and uric acid stone formers. AB - Many biological functions follow circadian rhythms driven by internal and external cues that synchronize and coordinate organ physiology to diurnal changes in the environment and behavior. Urinary acid-base parameters follow diurnal patterns and it is thought these changes are due to periodic surges in gastric acid secretion. Abnormal urine pH is a risk factor for specific types of nephrolithiasis and uric acid stones result from excessively low urine pH. Here we placed 9 healthy volunteers and 10 uric acid stone formers on fixed metabolic diets to study the diurnal pattern of urinary acidification. All showed clear diurnal trends in urinary acidification, but none of the patterns were affected by inhibitors of the gastric proton pump. Uric acid stone formers had similar patterns of change throughout the day but their urine pH was always lower compared to healthy volunteers. Uric acid stone formers excreted more acid (normalized to acid ingestion), with the excess excreted primarily as titratable acid rather than ammonium. Urine base excretion was also lower in uric acid stone formers (normalized to base ingestion), along with lower plasma bicarbonate concentrations during part of the day. Thus, increased net acid presentation to the kidney and the preferential use of buffers, other than ammonium, result in much higher concentrations of undissociated uric acid throughout the day and consequently an increased risk of uric acid stones. PMID- 22297672 TI - Integrin alpha1/Akita double-knockout mice on a Balb/c background develop advanced features of human diabetic nephropathy. AB - Animal models that mimic human diabetic nephropathy are useful to identify key factors in pathogenesis of this disease, as well as the development of new therapies. Several mouse models of diabetes have features of human diabetic nephropathy, yet none of these completely fulfill the Animal Models of Diabetes Complications Consortium criteria and completely reproduce pathological and functional features of the human disease. The Akita mouse carries a mutation in the insulin-2 gene and, to date, only survives as heterozygotes that develop spontaneous type 1 diabetes. Here we show that Akita mice with mutation of both insulin-2 alleles (Akita knockout (KO)) survive if crossed onto the Balb/c background. These mice develop hyperglycemia, more severe albuminuria, and mesangial sclerosis compared with heterozygous mice on the same genetic background. Interestingly, crossing these AkitaKO mice with integrin alpha1KO mice, a model of exacerbated glomerulosclerosis after injury and also on the Balb/c background, resulted in a 16-fold increase in albuminuria, significant mesangial matrix expansion, nodular and diffuse glomerulosclerosis, and a 2-fold increase in glomerular basement membrane thickening when compared with nondiabetic mice. Moreover, a significant decline in glomerular filtration was evident in the alpha1KOAkitaKO mice at 6 months of age. Thus, the integrin alpha1KOAkitaKO Balb/c mouse represents a promising model presenting with most features of human diabetic nephropathy. PMID- 22297673 TI - Dialysis outcomes and analysis of practice patterns suggests the dialysis schedule affects day-of-week mortality. AB - The risk of death for hemodialysis patients is thought to be highest on the days following the longest interval without dialysis (usually Mondays and Tuesdays); however, existing results are inconclusive. To clarify this we analyzed Dialysis Outcomes and Practice Patterns Study (DOPPS) data of 22,163 hemodialysis patients from the United States, Europe, and Japan. Our study focused on the association between dialysis schedule and day of the week of all-cause, cardiovascular, and noncardiovascular mortality with day-of-week coded as a time-dependent covariate. The models were adjusted for dialysis schedule, age, country, DOPPS phase I or II, and other demographic and clinical covariates, and compared mortality on each day to the 7-day average. Patients on a Monday-Wednesday-Friday (MWF) schedule had elevated all-cause mortality on Mondays, and those on a Tuesday-Thursday Saturday (TTS) schedule had increased risk of mortality on Tuesdays in all three regions. The association between day-of-week mortality and schedule was generally stronger for cardiovascular than noncardiovascular mortality, and was most pronounced in the United States. Unexpectedly, Japanese patients on a MWF schedule had a higher risk of noncardiovascular mortality on Fridays, and European patients on a TTS schedule experienced an elevated cardiovascular mortality on Saturdays. Thus, future studies are needed to evaluate the influence of practice patterns on schedule-specific mortality and factors that could modulate this effect. PMID- 22297674 TI - Calcium balance in normal individuals and in patients with chronic kidney disease on low- and high-calcium diets. AB - Calcium balance in chronic kidney disease is poorly understood as calcium deficiency is a stimulus for secondary hyperparathyroidism and consequent bone loss while calcium excess promotes extraosseous calcifications. To help resolve this, we evaluated calcium balance in normal individuals and in patients with chronic kidney disease (CKD) on daily diets containing 800 and 2000 mg elemental calcium. Both normal individuals and patients with late stage 3 and stage 4 CKD were in slightly negative to neutral calcium balance on the 800-mg calcium diet. Normal individuals were in modest positive calcium balance on the 2000-mg diet, while patients with CKD on the same diet were in marked positive calcium balance at least over the 9 days of study; and significantly greater than the normal individuals. Increased calcium intake significantly decreased 1,25-dihydroxy vitamin D and intact parathyroid hormone levels but did not alter the serum calcium concentration. Thus, our findings have important implications for both preventing calcium deficiency and loading in individuals with late stage 3 and stage 4 CKD. PMID- 22297675 TI - Toll-like receptors in transplantation: sensing and reacting to injury. AB - Toll-like receptors (TLRs) are a family of transmembrane proteins that have a major role in pathogen-induced inflammation and orchestrating an organism's defense against infection. Data are emerging that the TLRs play an important role as a first response to tissue injury linking the innate with the adaptive immune system. The recognition that TLRs are expressed on nonimmune cells including renal and liver cells, and that endogenous, cell-derived ligands (damage associated molecular patterns) can signal through specific TLRs has expanded the understanding of how these receptors impact a variety of diseases. This review focuses on recent findings elucidating the ability of TLRs to affect transplant outcomes. Specifically, observations demonstrating the link between endogenous TLR ligands and IR injury, how this can affect alloimmunity and transplant tolerance, and therapeutic implications will be discussed. PMID- 22297676 TI - Anti-DNA autoantibodies initiate experimental lupus nephritis by binding directly to the glomerular basement membrane in mice. AB - The strongest serological correlate for lupus nephritis is antibody to double stranded DNA, although the mechanism by which anti-DNA antibodies initiate lupus nephritis is unresolved. Most recent reports indicate that anti-DNA must bind chromatin in the glomerular basement membrane or mesangial matrix to form glomerular deposits. Here we determined whether direct binding of anti-DNA antibody to glomerular basement membrane is critical to initiate glomerular binding of anti-DNA in experimental lupus nephritis. Mice were co-injected with IgG monoclonal antibodies or hybridomas with similar specificity for DNA and chromatin but different IgG subclass and different relative affinity for basement membrane. Only anti-DNA antibodies that bound basement membrane bound to glomeruli, activated complement, and induced proteinuria whether injected alone or co-injected with a non-basement-membrane-binding anti-DNA antibody. Basement membrane-binding anti-DNA antibodies co-localized with heparan sulfate proteoglycan in glomerular basement membrane and mesangial matrix but not with chromatin. Thus, direct binding of anti-DNA antibody to antigens in the glomerular basement membrane or mesangial matrix may be critical to initiate glomerular inflammation. This may accelerate and exacerbate glomerular immune complex formation in human and murine lupus nephritis. PMID- 22297677 TI - Lower serum bicarbonate and a higher anion gap are associated with lower cardiorespiratory fitness in young adults. AB - Lower levels of serum bicarbonate and a higher anion gap have been associated with insulin resistance and hypertension in the general population. Whether these associations extend to other cardiovascular disease risk factors is unknown. To clarify this, we examined the association of serum bicarbonate and anion gap with cardiorespiratory fitness in 2714 adults aged 20-49 years in the 1999-2004 National Health and Nutrition Examination Survey. The mean serum bicarbonate was 24.6 mEq/l and the mean anion gap was 10.26 mEq/l, with fitness determined by submaximal exercise testing. After multivariable adjustment, gender, length of fasting, soft drink consumption, systolic blood pressure, serum phosphate, and hemoglobin were independently associated with both the serum bicarbonate and the anion gap. Low fitness was most prevalent among those in the lowest quartile of serum bicarbonate or highest quartile of anion gap. After multivariable adjustment, a 1 s.d. higher serum bicarbonate or anion gap was associated with an odds ratio for low fitness of 0.80 (95% CI 0.70-0.91) and 1.30 (95% CI 1.15 1.48), respectively. The association of bicarbonate with fitness may be mediated by differences in lean body mass. Thus, lower levels of serum bicarbonate and higher levels of anion gap are associated with lower cardiorespiratory fitness in adults aged 20-49 years in the general population. PMID- 22297678 TI - Low birth weight is associated with earlier onset of end-stage renal disease in Danish patients with autosomal dominant polycystic kidney disease. AB - Low-birth-weight individuals have a higher risk of hypertension and end-stage renal disease (ESRD). Here we investigated whether low birth weight was associated with earlier onset of ESRD in patients with autosomal dominant polycystic kidney disease (ADPKD). In collaboration with all Danish departments of nephrology, 307 of 357 patients with ADPKD and ESRD born and living in Denmark were recruited. We were able to analyze complete data of 284 patients obtained from both hospital medical files and midwife protocols in the Danish State Archives. Multivariable linear regression adjusted for birth weight, adult height, mean arterial pressure, gender, birth decade, and type of antihypertensive treatment showed that for every kilogram increase in birth weight, the age at onset of ESRD significantly increased by 1.7 years. Male gender and increased mean arterial pressure were both associated with earlier onset of ESRD. Patients treated with renin-angiotensin system blockade or calcium channel blockers during follow-up had significantly later onset of ESRD by 4.3 years and 2.1 years, respectively. Treatment with beta-blockade or a diuretic was not associated with the age at onset of ESRD. Thus, low birth weight may contribute to considerable phenotypic variability in the progression of renal disease between individuals with ADPKD. PMID- 22297679 TI - Post-streptococcal glomerulonephritis is a strong risk factor for chronic kidney disease in later life. AB - Although unusual in western countries and in Australia in general, post streptococcal glomerulonephritis (PSGN) is still common in Australian Aboriginal children living in remote communities. Here, we evaluated whether episodes of acute PSGN increased the risk for chronic kidney disease in later life in 1519 residents of a remote Aboriginal community (85% of those age eligible), with high rates of renal and cardiovascular disease, who participated in a health screen over a 3-year period. Of these, 200 had had at least one episode of PSGN, with 27 having had multiple episodes, usually in childhood. High levels of albuminuria (albumin/creatinine ratio) with increasing age were confirmed. All PSGN episodes were associated with group A streptococcal skin infections, often related to scabies. In both genders, aged 10-39 years at screening, about one in five had such a history. Among them, PSGN (5 years or more earlier) was significantly associated with higher levels of albuminuria than those without. In women, aged 30-39 years, a history of PSGN was associated with a significantly higher frequency of estimated glomerular filtration rates <60 ml/min. The adjusted odds ratios for an albumin/creatinine ratio over 34 g/mol (overt albuminuria) in males and females with a history of PSGN were 4.6 and 3.1, respectively, compared with those without a history. Thus, PSGN contributes to the very serious burden of chronic kidney disease in this community. Rigorous strategies to prevent scabies and Group A streptococcal infections will reduce this burden. PMID- 22297680 TI - Inhibition of eNOS phosphorylation mediates endothelial dysfunction in renal failure: new effect of asymmetric dimethylarginine. AB - Patients with chronic kidney disease have elevated circulating asymmetric dimethylarginine (ADMA). Recent studies have suggested that ADMA impairs endothelial nitric oxide synthase (eNOS) by effects other than competition with the substrate L-arginine. Here, we sought to identify the molecular mechanism by which increased ADMA causes endothelial dysfunction in a chronic kidney disease model. In wild-type mice with remnant kidney disease, blood urea nitrogen, serum creatinine, and ADMA were increased by 2.5-, 2-, and 1.2-fold, respectively, without any change in blood pressure. Nephrectomy reduced endothelium-dependent relaxation and eNOS phosphorylation at Ser1177 in isolated aortic rings. In transgenic mice overexpressing dimethylarginine dimethylaminohydrolase-1, the enzyme that metabolizes ADMA, circulating ADMA was not increased by nephrectomy and was decreased to half that of wild-type mice. These mice did not exhibit the nephrectomy-induced inhibition of both endothelium-dependent relaxation and eNOS phosphorylation. In cultured human endothelial cells, agonist-induced eNOS phosphorylation and nitric oxide production were decreased by ADMA at concentrations less than that of L-arginine in the media. Thus, elevated circulating ADMA may be a cause, not an epiphenomenon, of endothelial dysfunction in chronic kidney disease. This effect may be attributable to inhibition of eNOS phosphorylation. PMID- 22297681 TI - Disseminated carcinoma ex pleomorphic adenoma in an adolescent confirmed by application of PLAG1 immunohistochemistry and FISH for PLAG1 rearrangement. AB - A 16-year-old previously asymptomatic boy presented with complaints of fatigue, weight loss, and back pain for several months. Imaging studies revealed a large superior mediastinal mass, numerous bilateral pulmonary nodules, and multiple lytic bone lesions. A needle biopsy from a sternal lesion showed a poorly differentiated carcinoma, immunoreactive for cytokeratins and EMA and immunonegative for various organ/tissue-specific markers.His past medical history was significant for excision of aparotid gland tumor 5 years earlier. Histologic review of the salivary gland tumor revealed a pleomorphic adenoma containing a microscopic focus of invasive carcinoma(carcinoma ex pleomorphic adenoma). By immunohistochemistry, both the salivary gland tumor and the disseminated carcinoma expressed PLAG1 with a strong nuclear pattern.Fluorescence in situ hybridization (FISH), using dual-color, break-apart probes for PLAG1, showed rearrangement of the gene in both the salivary gland and the disseminated tumors.FISH demonstrated additional cytogenetic aberrations in the carcinoma, including polysomy for chromosome 8 (in both the primary salivary gland and the metastatic tumors) and PLAG1 amplification (in the metastatic tumor). We conclude that in the proper clinicopathologic setting, application of PLAG1 immunohistochemistry and FISH for PLAG1 gene rearrangement may be valuable in establishing the diagnosis of carcinoma ex pleomorphic adenoma as the source of a cancer of unknown primary site. PMID- 22297682 TI - Probing Y-shaped DNA structure with time-resolved FRET. AB - Self-assembly based on nucleic acid systems has become highly attractive for bottom-up fabrication of programmable matter due to the highly selective molecular recognition property of biomolecules. In this context, Y-shaped DNA (Y DNA) provides an effective building block for forming unique self-assembled large scale architectures. The dimension and growth of the nano- and microstructures depend significantly on the configurational stability of Y-DNA as a building block. Here we present structural studies of Y-DNA systems using a time-resolved FRET (Forster resonance energy transfer) technique. A fluorophore (Alexa 488) and an acceptor (DABCYL) were placed at two different ends of Y-DNA, and the lifetime of the fluorophore was measured to probe the relative distance between the donor and acceptor. Our results confirmed different distances between the arms of the Y DNA and highlighted the overall structural integrity of the Y-DNA system as a leading building block for molecular self-assembly. Temperature dependent lifetime measurements indicated configurational changes in the overall Y-DNA nanoarchitecture above 40 degrees C. PMID- 22297683 TI - Blood glutamate scavengers prolong the survival of rats and mice with brain implanted gliomas. AB - L-Glutamate (Glu) plays a crucial role in the growth of malignant gliomas. We have established the feasibility of accelerating a naturally occurring brain to blood Glu efflux by decreasing blood Glu levels with intravenous oxaloacetate, the respective Glu co-substrate of the blood resident enzyme humane glutamate oxaloacetate transaminase (hGOT). We wished to demonstrate that blood Glu scavenging provides neuroprotection in the case of glioma. We now describe the neuroprotective effects of blood Glu scavenging in a fatal condition such as brain-implanted C6 glioma in rats and brain-implanted human U87 MG glioma in nude mice. Rat (C-6) or human (U87) glioma cells were grafted stereotactically in the brain of rats or mice. After development of tumors, the animals were drinking oxaloacetate with or without injections of hGOT. In addition, mice were treated with combination treatment, which included drinking oxaloacetate with intracutaneous injections of hGOT and intraperitoneal injection of Temozolomide. Animals drinking oxaloacetate with or without injections of hGOT displayed a smaller tumor volume, reduced invasiveness and prolonged survival than control animals drinking saline. These effects were significantly enhanced by Temozolomide in mice, which increased survival by 237%. This is the first demonstration of blood Glu scavenging in brain cancer, and because of its safety, is likely to be of clinical significance for the future treatment of human gliomas. As we demonstrated, the blood glutamate scavenging treatment in combination with TMZ could be a good candidate or as an alternative treatment to the patients that do not respond to TMZ. PMID- 22297684 TI - Determination of domperidone in human plasma using liquid chromatography coupled to tandem mass spectrometry and its pharmacokinetic study. AB - A sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of domperidone (CAS number: 57808-66-9) in human plasma using paracetamol (CAS number: 103-90-2) as an internal standard (IS). Domperidone and paracetamol in plasma were extracted with ethyl acetate, separated on a C18 reversed phase column, eluted with mobile phase of acetonitrile-glacial acetic acid (0.3%) (40:60, v/v), ionized by positive ion pneumatically assisted electrospray and detected in the multi-reaction monitoring mode using precursor >product ions of m/z 426.2->175.1 for domperidone and 152->110 for the IS, respectively. The calibration curve was linear (r2>=0.99, n=5) over the concentration range of 0.2-80 ng/mL and with lower limit of detection and quantitation of 0.05 and 0.2 ng/mL. The specificity, matrix effect, recovery, sensitivity, linearity, accuracy, precision, and stabilities were validated for domperidone in human plasma. In conclusion, the validation results showed that this method was sensitive, economical and less toxic and it can successfully fulfill the requirement of clinical pharmacokinetic study of domperidone oral preparation in Chinese healthy volunteers. PMID- 22297686 TI - Engineering the work function of armchair graphene nanoribbons using strain and functional species: a first principles study. AB - First principles density functional theory calculations were performed to study the effects of strain, edge passivation, and surface functional species on the structural and electronic properties of armchair graphene nanoribbons (AGNRs), with a particular focus on the work function. The work function was found to increase with uniaxial tensile strain and decrease with compression. The variation of the work function under strain is primarily due to the shift of the Fermi energy with strain. In addition, the relationship between the work function variation and the core level shift with strain is discussed. Distinct trends of the core level shift under tensile and compressive strain were discovered. For AGNRs with the edge carbon atoms passivated by oxygen, the work function is higher than for nanoribbons with the edge passivated by hydrogen under a moderate strain. The difference between the work functions in these two edge passivations is enlarged (reduced) under a sufficient tensile (compressive) strain. This has been correlated to a direct-indirect bandgap transition for tensile strains of about 4% and to a structural transformation for large compressive strains at about - 12%. Furthermore, the effect of the surface species decoration, such as H, F, or OH with different covering density, was investigated. It was found that the work function varies with the type and coverage of surface functional species. Decoration with F and OH increases the work function while H decreases it. The surface functional species were decorated on either one side or both sides of AGNRs. The difference in the work functions between one-sided and two sided decorations was found to be relatively small, which may suggest an introduced surface dipole plays a minor role. PMID- 22297687 TI - Clinical decision support to promote safe prescribing to women of reproductive age: a cluster-randomized trial. AB - BACKGROUND: Potentially teratogenic medications are frequently prescribed without provision of contraceptive counseling. OBJECTIVE: To evaluate whether computerized clinical decision support (CDS) can increase primary care providers' (PCPs') provision of family planning services when prescribing potentially teratogenic medications. DESIGN: Cluster-randomized trial conducted in one academic and one community-based practice between October of 2008 and April of 2010. PARTICIPANTS/INTERVENTIONS: Forty-one PCPs were randomized to receive one of two types of CDS which alerted them to risks of medication-induced birth defects when ordering potentially teratogenic medications for women who may become pregnant. The 'simple' CDS provided a cautionary alert; the 'multifaceted' CDS provided tailored information and links to a structured order set designed to facilitate safe prescribing. Both CDS systems alerted PCPs about medication risk only once per encounter. MAIN MEASURES: We assessed change in documented provision of family planning services using data from 35,110 encounters and mixed effects models. PCPs completed surveys before and after the CDS systems were implemented, allowing assessment of change in PCP-reported counseling about the risks of medication-induced birth defects and contraception. KEY RESULTS: Both CDS systems were associated with slight increases in provision of family planning services when potential teratogens were prescribed, without a significant difference in improvement by CDS complexity (p = 0.87). Because CDS was not repeated, 13% of the times that PCPs received CDS they substituted another potential teratogen. PCPs reported significant improvements in several counseling and prescribing practices. The multifaceted group reported a greater increase in the number of times per month they discussed the risks of medication use during pregnancy (multifaceted: +4.9 +/- 7.0 vs. simple: +0.8 +/- 3.2, p = 0.03). The simple CDS system was associated with greater clinician satisfaction. CONCLUSIONS: CDS systems hold promise for increasing provision of family planning services when fertile women are prescribed potentially teratogenic medications, but further refinement of these systems is needed. PMID- 22297688 TI - Characterization and validation of a Portuguese natural reference soil to be used as substrate for ecotoxicological purposes. AB - This study describes the first attempt to validate a Portuguese natural soil (PTRS1) to be used as reference soil for ecotoxicological purposes, aimed to both: (i) obtain ecotoxicological data for the derivation of Soil Screening Values (SSVs) with regional relevance, acting as a substrate to be spiked with ranges of concentrations of the chemicals under evaluation and (ii) act as control and as substrate for the dilution of contaminated soils in ecotoxicological assays performed to evaluate the ecotoxicity of contaminated soils, in tier 2 of risk assessment frameworks, applied to contaminated lands. The PTRS1 is a cambisol from a granitic area integrated in the Central Iberian Zone. After chemical characterization of the soil in terms of pseudo-total metals, PAHs, PCBs and pesticide contents, it was possible to perceive that some metals (Ba, Be, Co, Cr and V) surpass the Dutch Target Values (Dtvs) corrected for the percentage of organic matter and clay of the PTRS1. Nevertheless, these metals displayed total concentrations below the background total concentrations described for Portuguese soils in general. The same was observed for aldrin, endosulfan I, endosulfan II, heptachlor epoxide, and heptachlor; however the Dtvs corrected become negligible. The performance of invertebrate and plant species, commonly used in standard ecotoxicological assays, was not compromised by both soil properties and soil metal contents. The results obtained suggest that the PTRS1 can be used as a natural reference soil in ecotoxicological assays carried out under the scope of ecological risk assessment. PMID- 22297689 TI - Differences of Z chromosome and genomic expression between early- and late feathering chickens. AB - One duplicated segment on chicken Z chromosome is a causal mutation to the late feathering phenotype. However, understanding biological process of the late feathering formation is also of interest to chicken breeding and feather development theory. One hundred and thirty-seven valid single nucleotide polymorphisms (SNPs) from an SNP database were used to perform an association study of the Z chromosome in Xinghua chickens. Two SNPs, which were respectively on 9607480 bp and 10607757 bp, were significantly associated with feathering phenotypes. This result indicated the causal mutation of the late-feathering formation in Xinghua chickens was consistent with the previous report which showed the late-feathering locus ranged 9966364-10142688 bp on Z chromosome. Microarray expressions were implemented for six 1-day-old female Xinghua chicks. Compared to the early-feathering chicks, there were 249 and 83 upregulated and downregulated known genes in the late-feathering chicks. Forty-one genes were expressed in late-feathering chicks, but not in early-feathering ones. At least 14 significantly differentially expressed genes were directly related to keratin. In the region of the sex-linked feathering gene, only prolactin receptor (PRLR) gene was a significantly differentially expressed gene. Expression of PRLR in late-feathering chicks was 1.78-fold as that in early-feathering chicks. Late feathering Wenchang chicks also had higher expression level of PRLR than early feathering ones. This study suggested that increasing PRLR expression that resulted from the special variant on chicken Z chromosome caused the late feathering phenotype. PMID- 22297690 TI - The proteome response of salt-resistant and salt-sensitive barley genotypes to long-term salinity stress. AB - Responses of plants to salinity stress and the development of salt tolerance are extremely complex. Proteomics is a powerful technique to identify proteins associated with a particular environmental or developmental signal. We employed a proteomic approach to further understand the mechanism of plant responses to salinity in a salt-tolerant (Afzal) and a salt-sensitive (Line 527) genotype of barley. At the 4-leaf stage, plants were exposed to 0 (control) or 300 mM NaCl. Salt treatment was maintained for 3 weeks. Total proteins of leaf 4 were extracted and separated by two-dimensional gel electrophoresis. More than 500 protein spots were reproducibly detected. Of these, 44 spots showed significant changes to salt treatment compared to the control: 43 spots were upregulated and 1 spot was downregulated. Using MALDI-TOF-TOF MS, we identified 44 cellular proteins have been identified, which represented 18 different proteins and were classified into seven categories and a group with unknown biological function. These proteins were involved in various many cellular functions. Up regulation of proteins which involved in reactive oxygen species scavenging, signal transduction, protein processing and cell wall may increase plant adaptation to salt stress. The upregulation of the three of four antioxidant proteins (thioredoxin, methionine sulfoxide reductase and dehydroascorbate reductase) in susceptible genotype Line 527 suggesting a different tolerance mechanism (such as tissue tolerance) to tolerate a salinity condition in comparison with the salt sensitive genotype. PMID- 22297691 TI - Interactions between CYP1A1 polymorphisms and cigarette smoking are associated with the risk of hepatocellular carcinoma: evidence from epidemiological studies. AB - The Cytochrome P-450 1A1 (CYP1A1) gene has been implicated in the etiology of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, a meta-analysis was performed to clarify the associations of polymorphisms in CYP1A1 gene with HCC risk. Published literature from PubMed, Embase, CNKI and Wanfang Data were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Eight studies (1,752 cases and 2,279 controls) for Ile-Val polymorphism and eight studies (933 cases and 1,449 controls) for MspI polymorphism were identified. The results showed that there was no statistically significant association between the Ile-Val polymorphism and HCC risk under all genetic models (co-dominant model: Val/Val vs. Ile/Ile: OR = 1.62, 95% CI 0.96-2.72 and Ile/Val vs. Ile/Ile: OR = 1.15, 95% CI 0.87-1.52; dominant model: OR = 1.25, 95% CI 0.92-1.70; recessive model: OR = 1.48, 95% CI 0.99-2.21). The MspI polymorphism was also not associated with HCC risk (co-dominant model: m2m2 vs. m1m1: OR = 1.09, 95% CI 0.83-1.42 and m1m2 vs. m1m1: OR = 1.30, 95% CI 1.05-1.61; dominant model: OR = 1.20, 95% CI 0.99-1.45; recessive model: OR = 0.94, 95% CI 0.74-1.18). However, the significant associations were found between both the Ile-Val and MspI polymorphisms and HCC risk among the cigarette smoking subjects (Ile-Val: OR = 1.40, 95% CI 1.06-1.85; MspI: OR = 2.65, 95% CI 1.47-4.77). The present meta analysis indicated that the MspI and Ile-Val polymorphisms of CYP1A1 may play important roles in increasing susceptibility to smoking-related HCC. PMID- 22297692 TI - Expression characteristics of two ubiquitin/ribosomal fusion protein genes in the developing testis, accessory gonad and ovary of Chinese mitten crab, Eriocheir sinensis. AB - The ubiquitin/proteasome pathway plays an important role in gametogenesis. Ubiquitin/ribosomal fusion protein is the precursor of mono-ubiquitin. We identified two ubiquitin/ribosomal fusion proteins genes in testis of Eriocheir sinensis. The ubiquitin-ribosomal proteins S27 and L40 are denoted as UBS27 and UBL40, respectively. The full length Es-UBS27 cDNA (565 bp) was cloned using PCR, based upon an initial expressed sequence tag (EST) isolated from a testicular cDNA library and the result of 3' RACE. The sequence contained a 465-nucleotide open reading frame (ORF) that encoded a protein of 154 amino acids. It contained a Ubiquitin (UB) domain and the ribosomal protein S27. The full-length Es-UBL40 cDNA (521 bp) contained a 390-nucleotide ORF that encoded a protein of 129 amino acids. It contained a UB domain and the ribosomal protein L40. By real-time PCR, the expression level of these two UB genes is shown to change significantly in the developing testis and ovary, reaching peak expression in August and October, respectively. During accessory gonad seasonal development, the expression of UBS27 and UBL40 varied sharply and reached peak expression in November. In situ hybridization of testis and ovary, indicated that UB transcription took place widely. Our study demonstrates, for the first time, that UBS27 and UBL40 play key roles in gametogenesis and reproductive success in Eriocheir sinensis. PMID- 22297693 TI - ACE2 gene polymorphism and essential hypertension: an updated meta-analysis involving 11,051 subjects. AB - The polymorphisms of angiotensin-converting enzyme 2 (ACE2) gene have been suggested to be linked to increase risk of essential hypertension in multiple populations. However, the results are still debatable. To assess the association between ACE2 G8970A genetic polymorphism and essential hypertension, we conducted a meta-analysis of case-control studies across different ethnicity. PubMed, Embase, CBM, Wanfang and VIP databases were searched, and a total of 11 separate studies in females and nine separate studies in males met the inclusion criteria. Because ACE2 is on the X chromosome, data for each sex were analyzed separately. The selected studies contained 7,251 (4,472 females/2,779 males) hypertensive patients and 3,800 (2,161 females/1,639 males) normotensive controls. A statistically significant association was observed between the G8970A gene polymorphism and essential hypertension risk in female hypertensive group in the recessive genetic model (AA vs. GG+GA: P = 0.03, OR = 1.15, 95% CI = 1.02-1.30, P(heterogeneity) = 0.40, I(2) = 5%, fixed-effects model). Although no association was shown between the frequency of the A allele and the genetic susceptibility to essential hypertension in all male patients (A Allele: P = 0.38, OR = 1.10, 95% CI = 0.89-1.38, P(heterogeneity) = 0.02, I(2) = 56%, random-effects model), we found that the relationship between carrier of A allele and the essential hypertension risk in Han-Chinese male patients subgroup (A Allele: P = 0.006, OR = 1.21, 95% CI = 1.06-1.38, P(heterogeneity) = 0.10, I(2) = 44%, fixed-effects model). The current meta-analysis provided solid evidence suggesting that ACE2 gene polymorphism G8790A was probably a genetic risk factor for essential hypertension across different ethnic populations in female subjects and in Han Chinese male subjects. PMID- 22297694 TI - Expressions of GRP78 and Bax associate with differentiation, metastasis, and apoptosis in non-small cell lung cancer. AB - The purpose of this study was to detect the expressions of GRP78 and Bax in human non-small cell lung cancer (NSCLC) tissues, to analyze their correlations with carcinogenesis and the development of NSCLC, and to investigate the relationship of GRP78 expression to metastasis and apoptosis in the NSCLC cell line HCC827. The positive expression rates of GRP78 and Bax in NSCLC lung tissues were 59.7% and 34.7% by RT-PCR, respectively. The mRNA and protein expression levels of GRP78 in NSCLC tissues were significantly higher than that in the relatively normal surrounding lung tissues (p < 0.05); the lesser the degree of tumor differentiation was, the higher the mRNA and protein expression levels of GRP78 were (p < 0.05). The mRNA and protein expression levels of GRP78 from patients in advanced pathological stages (III-IV) were significantly higher than the corresponding levels in patients in early pathological stages (I-II) (p < 0.05); the mRNA and protein expression levels of GRP78 in patients with positive lymph node metastasis were significantly higher than those in patients with negative lymph node metastasis (p < 0.05). The mRNA and protein expression levels of Bax in the above cases showed the opposite trend of the mRNA and protein expression levels of GRP78. However, the mRNA and protein expression levels of both GRP78 and Bax were independent of the patient's sex, the patient's age, the tumor size and the histological type (adenocarcinoma or squamous cell carcinoma) of NSCLC (p > 0.05). The mRNA expression level of GRP78 and the mRNA expression level of Bax in human NSCLC tissues were negatively correlated (r = -0.353, p = 0.002). After transfection of GRP78 siRNA in HCC827 cells, the GRP78 protein expression level was significantly decreased (p < 0.01), while the Bax protein expression level was significantly increased (p < 0.01); the number of cells that passed through the Transwell chamber was significantly less in the non-transfected control group compared to the transfected control group (p < 0.01). The number of apoptotic cells was significantly greater in the non-transfected control group compared to the transfected control group (p < 0.01). The expression levels of GRP78 and Bax were related to the carcinogenesis, development and metastasis of NSCLC. GRP78 expression with siRNA interference in the human NSCLC cell line HCC827 can reduce metastasis and promote apoptosis in HCC827 cells. PMID- 22297695 TI - Association between the COMT Val158Met polymorphism and breast cancer risk: a meta-analysis of 30,199 cases and 38,922 controls. AB - Many studies have reported the role of COMT Val158Met with breast cancer risk, but the results remained controversial. In addition, previous meta-analysis on COMT Val158Met showed conflicting results. Hence, we performed a meta-analysis to investigate the association between breast cancer and COMT Val158Met (30,199 cases and 38,922 controls) in different inheritance models. When all the eligible studies were pooled into this meta-analysis, there was no evidence of significant association between breast cancer risk and COMT Val158Met polymorphism in any genetic model (dominant model: odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.94-1.04, P value of heterogeneity test [P(h)] = 0.009, I(2) = 36.9%; recessive model: OR = 0.97, 95% CI = 0.92-1.02, P(h) = 0.044, I(2) = 28.6%; additive model: OR = 0.98, 95% CI = 0.91-1.05, P(h) = 0.004, I(2) = 40.4%). However, significant between-study heterogeneity was detected in any genetic model. Hence, we performed the stratified analysis according to ethnicity, source of controls, menopausal status, and family history. In the stratified analysis by ethnicity significantly decreased breast cancer risk was observed in Caucasian population (recessive model: OR = 0.96, 95% CI = 0.92-1.00, P(h) = 0.419, I(2) = 3.1%). In conclusion, this meta-analysis indicates that COMT Val158Met polymorphism may be associated with decreased breast cancer risk in Caucasian population. However, a study with the larger sample size is needed to further evaluated gene-environment interaction on COMT Val158Met polymorphisms and breast cancer risk. PMID- 22297696 TI - Alkalilactibacillus ikkensis, gen. nov., sp. nov., a novel enzyme-producing bacterium from a cold and alkaline environment in Greenland. AB - Three novel Gram-positive, endospore-forming bacteria were isolated from a cold and alkaline environment. Phylogenetic analysis showed that the strains were almost identical, and that they were related to Natronobacillus azotifigens 24KS 1(T) (95.8% identity), Paraliobacillus quinghaiensis YIM-C158(T) (95.1%), Paraliobacillus ryukyuensis O15-7(T) (94.5%), and Halolactibacillus miurensis M23 1(T) (93.9%). The isolates produced amylase, alpha-galactosidase, beta galactosidase, and beta-glucuronidase, and showed optimal growth at pH 10, at 20 degrees C, and at 2-8% (w/v) NaCl. Major fatty acids were C(14:0) (10.6-11.6%), anteiso-C(15:0) (25.7-32.7%), C(16:1) omega11c (12.2-16.0%), and C(16:0) (14.0 20.4%). The major polar lipids were diphosphatidylglycerol and phosphatidylglycerol, and meso-diaminopimelic acid was found in the cell-wall peptidoglycan. The G+C content was 38.4%. DNA-DNA hybridization between strain GCM68(T) and H. miurensis M23-1(T) was 32.4%, while hybridization to N. azotifigens 24KS-1(T), Amphibacillus tropicus Z-7792(T), and Paraliobacillus ryukyuensis O15-7(T) was below 30%. The phylogenetic analysis and G+C content place strain GCM68(T) in relation to species belonging to Bacillus rRNA group 1, but phylogenetic and physiologic data combined with chemotaxonomic analyses support our proposal for a new genus, Alkalilactibacillus, gen. nov., with the novel species Alkalilactibacillus ikkensis, sp. nov. (type strain is GCM68(T) = DSM 19937 = LMG 24405). PMID- 22297697 TI - Culturable bacteria isolated from snow cores along the 1300 km traverse from Zhongshan Station to Dome A, East Antarctica. AB - The abundance and community composition of culturable bacteria in four snow cores along the 1300 km traverse from Zhongshan Station to Dome A, East Antarctica, were investigated through the combination of liquid and solid media and small subunit 16S rRNA sequences. Under aerobic cultivation conditions, the average concentrations of bacterial colonies from each snow core varied from 0.008 to 0.32 CFU mL(-1). A total of 37 and 15 isolates with different morphologic characteristics were recovered from solid and liquid media PYGV, respectively. The phylogenetic analysis of 14 representatives with different ARDRA patterns from RFLP showed that all the isolates were affiliated with five phylogenetic groups: Firmicutes, Actinobacteria, Alphaproteobacteria, Gammaproteobacteria and Bacteroidetes. Actinobacteria represented the largest cluster with 43% of strains, and these strains exhibited unique phenotypic properties. The community compositions of culturable bacteria in the four snow cores were distinctly different from each other and the concentrations and community sizes of culturable bacteria along the traverse decreased with increases of latitude, altitude and distance from coast, which likely reflected the different bacterial sources and biogeographies under the different regional climate conditions in the snow cover of East Antarctica. PMID- 22297698 TI - Si/poly-CuTAPC coaxial core-shell nanowire array as enhanced visible-light photocatalyst for hydrogen production. AB - A controllable method for coating a dense layer of poly-CuTAPc polymer on the surface of silicon nanowire array was reported and it is shown that the coating of poly-CuTAPc can effectively enhance both the photocatalytic hydrogen generation efficiency and the operation stability. PMID- 22297699 TI - Evaluation of cytotoxicity of a new hemostatic agent Ankaferd Blood Stopper(r) using different assays. AB - The aim of this study is to investigate the effects of the Ankaferd Blood Stopper(r) (ABS), on cell viability, cytotoxicity, and erythrocyte numbers in in vitro cultured human blood cells. We studied the cytotoxic effects of the ABS using lactate dehydrogenase (LDH) assay, cell proliferation (WST-1) assay and hemolytic assay. The cytotoxicity increased when cells were treated with ABS dilutions of 5%, 12.5%, 25%, and 50% (p < 0.05). Moreover, treatment of the cells with the same concentrations significantly elevated the cell number at 24 and 48 h (p < 0.05). ABS causes a significant increase (p < 0.05) in the hemolytic activity on human erythrocytes and hemolytic activity increases with increase in ABS concentrations. The red blood cell aggregation and cell membrane disruption during the coagulation process lead to induction of hemolytic activity and increase of LDH level in cell culture medium. In addition, ABS has proliferative effects on human leukocytes. Based on these results, ABS can be used as an alternative blood stopping agent safely. PMID- 22297700 TI - Venous thrombosis following intravenous injection of household bleach. AB - Sodium hypochlorite (NaClO) is used extensively as a disinfectant or bleaching agent. Most studies describe ingestion or inhalation route of this product with rare complication and fatalities. Despite global daily exposures, data about bleach injection is limited. Here we report intentional infusion of 20 mL, sodium hypochlorite 5% diluted in 500 mL normal saline 1.5 h prior admission. Clinical manifestation included local pain and edema. There were no laboratory abnormalities in the patient. Doppler sonography revealed thrombosis in superficial (antecubital and basilic) veins. Limb elevation, warm compress, and ibuprofen relived pain and edema after 3 days. PMID- 22297701 TI - The effects of cold-induced stress on liver oxidative injury during binge drinking. AB - The aim of our study was to evaluate the effects of cold stress on hepatic oxidative damage during binge drinking in rats. Male Wistar rats were divided into the following groups: group 1: control; group 2: ethanol-treated; group 3: stress-exposed; group 4: stress-exposed and ethanol-treated group. Oxidative and nitrosative stress parameters in the liver were determined spectrophotometrically, 12 h after treatment. Liver malondialdehyde concentration was significantly higher in group 4 when compared with groups 2 and 3. The highest increase in nitric oxide concentration was demonstrated in group 4 in comparison with groups 2 and 3. Superoxide dismutase (SOD) activity was significantly lower in group 4 when compared with groups 2 and 3. Ethanol administration induced a larger decrease in the activity of copper-/zinc-SOD in group 4 in comparison with group 2. Activity of manganese-SOD (Mn-SOD) was significantly higher in groups 3 and 4, when compared with control values, but the greatest increase in the activity of Mn-SOD was demonstrated in group 2. We also evaluated statistically significant decrease in the level of reduced gluthatione in the liver of group 4 in comparison with group 3. Based on our study, it can be concluded that cold-exposed stress and binge ethanol drinking have additive effects in imbalance between pro-oxidant and antioxidant defense system in liver. PMID- 22297702 TI - Study on the cytogenetic changes induced by benzene and hydroquinone in human lymphocytes. AB - Benzene (BN) is a prototypical hematotoxicant, genotoxic carcinogen, and ubiquitous environmental pollutant. Although the molecular mechanisms of BN induced cytotoxicity and genotoxic damage are poorly understood in humans, previous studies suggested that bioactivated BN metabolites are capable of oxidative stress, cell cycle arrest, apoptosis, and DNA damage. The objective of the current study was to investigate the BN-induced cytogenetic changes and underlying mechanisms based on these hypotheses. Peripheral blood lymphocytes (PBLs) might be the targets for BN-induced cytotoxicity and genotoxicity, and therefore DNA damage responses of PBLs after exposure to different concentrations of BN (0.25, 3.5, 50 MUmol/L) or BN metabolite, hydroquinone (HQ; 50, 150, 450 MUmol/L) were studied in vitro. Microculture tetrazolium assay, flow cytometry, 2',7'-dichlorodihydrofluorescein-diacetate assay, comet assay, micronuclei assay, and attenuated total reflectance microspectroscope were chosen for this study. Based on the results, we reached the conclusion that different concentrations of BN or HQ significantly inhibited cell growth, induced the arrest of S phase and G2/M phase, and increased late apoptosis in a concentration-dependent manner. Furthermore, evidence was also provided to support the conclusion that BN and HQ induced DNA strand breaks and chromosomal mutations in PBL, which indicated the genotoxicity of BN and HQ. Current evidence has indicated that multiple mechanisms including dysfunction of cell cycle, programmed cell death, oxidative stress, and DNA lesions are likely to contribute to BN-induced cytogenetic changes. PMID- 22297703 TI - Comparative tight junction protein expressions in colonic Crohn's disease, ulcerative colitis, and tuberculosis: a new perspective. AB - We intended to see the pattern of TJ protein expression along with ultrastructural changes in colonic biopsies from patients with Crohn's disease (CD), ulcerative colitis (UC), and tuberculosis (cTB). Colonic biopsies from 11 patients with active CD and ten patients each with active UC and untreated cTB were taken along with biopsies from six patients with irritable bowel syndrome as controls. These were evaluated for expression pattern of key TJ proteins which included claudin-2 as TJ pore-forming protein, claudin-4 as pore-sealing protein, ZO-1 as scaffold protein, and occludin as TJ protein related to cell migration and polarity. Claudin-2 expression was upregulated along the whole length of intercellular junction (ICJ) in biopsies from patients with active CD and UC in comparison to the biopsies from cTB patients and controls, where its expression was limited to the uppermost part of ICJ. There was reduced expression of ZO-1 in UC, CD, and cTB. On transmission electron microscopic examination, the pentalaminar structure of TJs was destroyed in patients with CD and UC but no significant change was seen in those with cTB and in controls. The expression of claudin-2 was distinctly different in active CD and UC in comparison to its expression pattern in patients with cTB and in controls. The redistribution of claudin-2 expression was in accordance with the TJ ultrastructural changes in patients with UC, CD, and cTB. Altered claudin-2 expression, along with destroyed TJs, may result in loss of selective permeability in patients with UC and CD. PMID- 22297704 TI - Pull-down of calmodulin-binding proteins. AB - Calcium (Ca(2+)) is an ion vital in regulating cellular function through a variety of mechanisms. Much of Ca(2+) signaling is mediated through the calcium binding protein known as calmodulin (CaM). CaM is involved at multiple levels in almost all cellular processes, including apoptosis, metabolism, smooth muscle contraction, synaptic plasticity, nerve growth, inflammation and the immune response. A number of proteins help regulate these pathways through their interaction with CaM. Many of these interactions depend on the conformation of CaM, which is distinctly different when bound to Ca(2+) (Ca(2+)-CaM) as opposed to its Ca(2+)-free state (ApoCaM). While most target proteins bind Ca(2+)-CaM, certain proteins only bind to ApoCaM. Some bind CaM through their IQ-domain, including neuromodulin, neurogranin (Ng), and certain myosins. These proteins have been shown to play important roles in presynaptic function, postsynaptic function, and muscle contraction, respectively. Their ability to bind and release CaM in the absence or presence of Ca(2+) is pivotal in their function. In contrast, many proteins only bind Ca(2+)-CaM and require this binding for their activation. Examples include myosin light chain kinase, Ca(2+)/CaM-dependent kinases (CaMKs) and phosphatases (e.g. calcineurin), and spectrin kinase, which have a variety of direct and downstream effects. The effects of these proteins on cellular function are often dependent on their ability to bind to CaM in a Ca(2+) dependent manner. For example, we tested the relevance of Ng-CaM binding in synaptic function and how different mutations affect this binding. We generated a GFP-tagged Ng construct with specific mutations in the IQ-domain that would change the ability of Ng to bind CaM in a Ca(2+)-dependent manner. The study of these different mutations gave us great insight into important processes involved in synaptic function. However, in such studies, it is essential to demonstrate that the mutated proteins have the expected altered binding to CaM. Here, we present a method for testing the ability of proteins to bind to CaM in the presence or absence of Ca(2+), using CaMKII and Ng as examples. This method is a form of affinity chromatography referred to as a CaM pull-down assay. It uses CaM Sepharose beads to test proteins that bind to CaM and the influence of Ca(2+) on this binding. It is considerably more time efficient and requires less protein relative to column chromatography and other assays. Altogether, this provides a valuable tool to explore Ca(2+)/CaM signaling and proteins that interact with CaM. PMID- 22297705 TI - A three-incision approach to treat persistent vaginal exposure and sinus tract formation related to ObTape mesh insertion. AB - Mentor Corporation's ObTape has been associated with considerable morbidity. An unacceptably high exposure rate has been noted, and in some cases, multiple procedures may be necessary for complete mesh removal.We evaluated a patient who had prior ObTape placement complicated with persistent vaginal discharge and granulation tissue formation related to persistent mesh exposure (3Bc-T2-S2) followed by sinus tract formation (6Cd-T3-S3) according to the International Urogynecological Association Classification. We performed a three-incision approach (abdominal, vaginal, and groin) for the complete removal of the retained portion of the transobturator tape. This three-incision technique represents a viable option for removal of transobturator tape causing persistent clinical issues. PMID- 22297706 TI - Alternative model of birth to reduce the risk of assisted vaginal delivery and perineal trauma. AB - INTRODUCTION AND HYPOTHESIS: This study was conducted to evaluate the effects of an alternative model of birth (AMB) on the incidence of assisted vaginal delivery (AVD) and perineal trauma (PT). METHODS: One hundred ninety-nine women with epidural anesthesia were randomized to a traditional model of birth (TMB) (n = 96) or AMB (n = 103). Women in TMB pushed immediately after complete dilatation and delivered in lithotomy position. In AMB, women followed a postural changes protocol while they delayed pushing and used a specific lateral position for delivery. RESULTS: AMB was associated with a significant reduction in AVD compared with TMB (19.8% vs 42.1%, p<0.001). TMB was strongly associated with AVD (OR = 4.49; p< 0.05), which, in turn, was significantly associated with nulliparity (OR = 5.52; p<0.005) and fetal head unengaged at full dilatation (OR = 5.35; p<0.05). AMB significantly increased the intact perineum rate compared with TMB (40.3% vs 12.2%, p<0.001). Episiotomy rate was significantly reduced in AMB (21.0% vs 51.4%, p<0.001). CONCLUSION: A combination of postural changes during the passive expulsive phase of labor and lateral position during active pushing time is associated with reductions in AVD and PT. PMID- 22297707 TI - Novel genetic mutation in the background of Carney complex. AB - Carney complex is a rare disease inherited in an autosomal dominant manner. It is mostly caused by inactivating mutations of the subunit of protein kinase A. Carney complex is associated with atrial myxoma, nevi or myxomas of the skin, breast tumor and endocrine overactivity. Primary pigmented nodular adrenocortical disease is the specific endocrine manifestation. The authors present the history of a 53-year-old female patient who had undergone surgery for atrial myxomas, thyroid tumor and breast cancer. She was also operated for an adrenal adenoma causing Cushing's syndrome. Genetic study revealed a novel mutation in the regulatory subunit of protein kinase A (ivs2-1G>A splice mutation in intron 2). Her heterozygous twins were also genetically screened and one of them carried the same mutation. The authors emphasize that despite the absence of specific treatment for patients with Carney complex, confirmation of the diagnosis by genetic studies is important for the close follow-up of the patient and early identification of novel manifestations. PMID- 22297708 TI - Non-platinum regimens of gemcitabine plus docetaxel versus platinum-based regimens in first-line treatment of advanced non-small cell lung cancer: a meta analysis on 9 randomized controlled trials. AB - PURPOSE: The aim was to compare the efficacy and toxicity of gemcitabine plus docetaxel (GD) with platinum-based regimens in patients with untreated advanced non-small cell lung cancer (NSCLC). METHODS: We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials databases for relevant trials. Reference lists of original articles and review articles were also examined. Abstracts presented at the ASCO and ESMO meetings were also searched. Studies were evaluated for eligibility and quality, and then, the data were extracted and analyzed. Statistical analyses were conducted by using RevMan 5.1. The primary end point was overall survival (OS). Secondary end points included 1-year survival, time to progression (TTP), overall response rate (ORR) and grade 3-4 toxicity. RESULTS: Nine randomized controlled trials were identified ultimately. The meta-analysis demonstrated that the survival between GD and platinum-based regimens was comparable according to the pooled HR for overall survival (1.04, 95% CI = 0.96-1.12, p = 0.39) and RR for one-year survival (0.94, 95% CI = 0.84 1.06, p = 0.33). Platinum-based regimens had an advantage in TTP (HR = 1.12, 95% CI = 1.02-1.24, p = 0.02) and ORR (RR = 0.86, 95% CI = 0.74-0.99, p = 0.03). However, GD induced less grade 3-4 nausea/vomiting, anemia, neutropenia and febrile neutropenia (RR = 0.36, 95% CI = 0.15-0.86, p = 0.02; RR = 0.35, 95% CI = 0.23-0.53, p = 0.00; RR = 0.68, 95% CI = 0.52-0.88, p = 0.003; RR = 0.53, 95% CI = 0.34-0.82, p = 0.004, respectively). Grade 3-4 diarrhea, sensory neuropathy, fatigue and thrombocytopenia were comparable between the two groups. CONCLUSIONS: GD acquired similar survival with platinum-based regimens in first-line treatment of advanced NSCLC. Platinum-based regimens had an advantage in TTP and ORR with more grade 3-4 nausea/vomiting, anemia, neutropenia and febrile neutropenia compared with GD. PMID- 22297709 TI - A combination of Botulinum Toxin A therapy and Functional Electrical Stimulation in children with cerebral palsy--a pilot study. AB - BACKGROUND: Among the ambulant population of children with spastic cerebral palsy (CP), dynamic equinus is one of the most common form of gait deviation that is encountered. OBJECTIVE: To investigate the combined effects of Functional Electrical Stimulation (FES) and Botulinum Toxin A (BTXA) therapy in children with spastic CP, and to demonstrate the feasibility of this combination therapy. METHODS: A single-subject design with repeated measures was adopted. Eight children (six males, two females; mean age 7 y 9 mo, SD 1 y 5 mo; range 7 y to 11 y) diagnosed with hemiplegic (n=6) or diplegic (n=2) spastic CP completed the study. Each subject participated in the study for twenty weeks. This period consisted of baseline (one week), BTXA phase (three weeks), first FES phase (four weeks), first control phase (four weeks), second FES phase (four weeks) and second control phase (four weeks). Subjects were assessed at the end of each phase. The ankle angle at the end of swing phase was selected as the primary outcome measure. The secondary outcome measure recorded was the foot contact pattern. RESULTS: There was an increase in ankle dorsiflexion at the end of the combined intervention in most subjects (n=6), accompanied by an improvement in foot contact pattern. CONCLUSIONS: This pilot study demonstrated that it is feasible to combine BTXA therapy with FES in ambulant children with spastic CP. PMID- 22297710 TI - Light therapy: methodological issues from an engineering perspective. AB - Light therapy is increasingly administered and studied as a non-pharmacologic treatment for a variety of health-related problems, including treatment of people with dementia. Light therapy comes in a variety of ways, ranging from being exposed to daylight, to being exposed to light emitted by light boxes and ambient bright light. Light therapy is an area in medicine where medical sciences meet the realms of physics, engineering and technology. Therefore, it is paramount that attention is paid in the methodology of studies to the technical aspects in their full breadth. This paper provides an extensive introduction for non technical researchers on how to describe and adjust their methodology when involved in lighting therapy research. A specific focus in this manuscript is on ambient bright light, as it is an emerging field within the domain of light therapy. The paper deals with how to (i) describe the lighting equipment, (ii) describe the light measurements, (iii) describe the building and interaction with daylight. Moreover, attention is paid to the uncertainty in standards and guidelines regarding light and lighting for older adults. PMID- 22297711 TI - A computerized intervention to promote colorectal cancer screening for underserved populations: theoretical background and algorithm development. AB - OBJECTIVE: The aim of this exploratory study was to assess factors deemed by patients as "important" as they planned and considered undergoing colorectal cancer (CRC) screening, and to use this data to design a computer-delivered intervention to promote screening. METHODS: Fifty participants 50 years or older, not up-to-date with current recommended CRC screening guidelines, were recruited from a primary care clinic. A semi-structured interview focused on aspects of preparing for colorectal cancer screening was administered; after transcription, researchers used triangulation and consensus to identify relevant themes and concepts. RESULTS: Four main themes were identified that dealt with issues important for both FOBT and colonoscopy planning: personal concerns, reminders, communication with healthcare providers and obtaining test results. FOBT specific themes included: sample collection and return. For colonoscopy screening, themes included: scheduling, intervention questions, colonoscopy preparation, and transportation. These can be classified as barrier, process and accessory themes. The developed computer-administered implementation intentions algorithm addressed all the identified concerns in a planned and sequential manner, in order to facilitate planning for CRC screening. CONCLUSIONS: The results of this study suggest that appropriate reminders, explanations of procedures, and patient understanding of temporary life disruptions, help patients develop and accept a detailed screening plan. PMID- 22297712 TI - Impact of enterococcus on immunocompetent and immunosuppressed patients with perforation of the small or large bowel. AB - INTRODUCTION AND METHODS: The role of enterococcus in intraabdominal infection remains controversial. A retrospective study of 473 patients with bowel perforation was conducted to assess the impact of enterococci on outcome of patients with perforation of the small and large bowel. RESULTS: The overall mean age was 61.4 with a gender ratio of 60/40 (m/f). We detected enterococci in 54% of all patients. In the group of enterococci-positive patients, we found Enterococcus faecalis (E. faecalis) in over 70% and Enterococcus faecium (E. faecium) in over 50%. Those in whom we detected enterococci (Pos) had a higher 90 day mortality rate than patients who were enterococci negative (Neg) (29.7%/19.4%, P 0.007). Morbidity, length of stay in intensive care unit (ICU LOS) and length of stay in hospital (hospital-LOS) were significantly higher in the Pos group. The subgroup of Pos who received specific antimicrobial therapy against these species (Pos-treated) had a higher 90-day mortality rate than the subgroup without specific therapy (Pos-not treated) (35.5%/23.3%, P 0.04). The Pos-not treated group had higher morbidity, ICU-LOS and hospital-LOS than the Neg group. The mortality rate, ICU-LOS and hospital-LOS of immunosuppressed patients (12%) were significantly higher compared with patients not on immunosuppression with similar morbidity. We found a higher rate of E. faecium than in other studies (55.1%). However, we observed no difference in mortality and morbidity between patients infected with E. faecalis and E. faecium. In multivariate analysis, detection of enterococci did not influence mortality. Significant risk factors were age, immunosuppression, specific antimicrobial therapy and anastomotic leakage. CONCLUSION: Enterococci seem to play a minor role in uncomplicated intraabdominal infections. Our results suggest that enterococci play a role in the severity of postoperative complications. In particular, detection of enterococci in patients with anastomotic leakage are suggested to be an indicator of severe illness. We found significantly higher rates of E. faecium than described before, but no significant differences in clinical outcome between E. faecalis and E. faecium. When empirical therapy against enterococci is recommended, E. faecalis and E. faecium should both be covered. PMID- 22297713 TI - Comparison of helicopter and ground emergency medical service: a retrospective analysis of a German rescue helicopter base. AB - BACKGROUND: In consideration of rising cost pressure in the German health care system, the usefulness of helicopter emergency medical service (HEMS) in terms of time- and cost-effectiveness is controversially discussed. The aim of the present study was to investigate whether HEMS is associated with significantly decreased arrival and transportation times compared to ground EMS. METHODS: In a retrospective study, we evaluated 1,548 primary emergency missions for time sensitive diagnoses (multiple trauma, traumatic brain and burn injury, heart attack, stroke, and pediatric emergency) performed by a German HEMS using the medical database, NADIN, of the German Air Rescue Service. Arrival and transportation times were compared to calculated ground EMS times. RESULTS: HEMS showed significantly reduced arrival times at the scene in case of heart-attack, stroke and pediatric emergencies. In contrast, HEMS and ground EMS showed comparable arrival times in patients with multiple trauma, traumatic brain and burn injury due to an increased flight distance. HEMS showed a significantly decreased transportation time to the closest centre capable of specialist care in all diagnosis groups (p<0.001). CONCLUSIONS: The results of the present study indicate the time-effectiveness of German air ambulance services with significantly decreased transportation times. PMID- 22297714 TI - Progress towards intra-operative measurement of femoral antetorsion. AB - Rotational malalignment following intramedullary nailing is a well-recognised problem. The threshold for clinically relevant malrotation has been established to be in the region of 15 degrees whereas the incidence of significant malrotation following femoral nailing ranges from 22 to 43 percent. Many studies have been performed to address this issue with the major challenge acknowledged to be intraoperative control of femoral anteversion. In the current study, the investigators developed and analysed a novel method to estimate the femoral antetorsion based on computed tomography (CT) data. They hypothesized that this method would be intra-operatively feasible and repeatable without further radiation. CT scans (n=166) of femoral neck fractures performed between 2005 and 2010 were evaluated. Twenty patients had a femoral neck fracture and thus were excluded. Every femoral neck was measured according the method described by Jend et al. and the current authors. In contrast to the Jend method, the current authors described femoral antetorsion as the angle between the ventral cortex of the femoral neck and the posterior condylar line. To determine this angle, the axial cuts from computed tomography data were studied. In order to maximise measurement consistencty among cases, the axial cut which displayed the intertrochanteric crest was selected. Mean femoral antetorsion is 12.15 degrees +/-10.04 degrees according to Jend et al. In comparison, a mean angle of 12.61 degrees +/-11.16 degrees was demonstrated in the current study. The absolute difference in measuring the femoral neck angle when these different methods are compared was 4.44 degrees . Statistically, there is no significant difference between the mean results for femoral antetorsion. The advantage of the method proposed in the current study, is the opportunity to enter the ventral femoral cortex during the surgical procedure without disturbing the process of femoral nailing. Thus, the surgeon can avail of continuous control of femoral rotation intra-operatively. PMID- 22297715 TI - Navigated femoral shaft fracture treatment: current status. AB - Femoral malrotation is a common complication after internal fixation of a femoral shaft fracture. The only valid, objective monitoring method is computer tomography-assisted torsion measurement between the proximal and distal femur; unfortunately, this can only be carried out postoperatively. A difference of 15 degrees compared to the contralateral femur is seen as an indication for revision. With the development of computer-assisted surgery, new possibilities for performing torsion control and correction intraoperatively has been introduced. These methods also allow for navigation-assisted definition of the optimal incision site, intramedullary access, femoral nail and interlocking. The main problem lies in the extra time of surgery, which is due to performing all the steps of the surgery navigated. The solution for this problem is "hybrid navigation", in which the surgeon can select the steps he needs from the navigation system, depending on his experience or surgical technique. PMID- 22297717 TI - Current world literature. PMID- 22297716 TI - Glutamatergic transmission in schizophrenia: from basic research to clinical practice. AB - PURPOSE OF REVIEW: The past 20 years have seen the glutamatergic hypothesis go from theory to phase III trials of novel mechanism antipsychotics. RECENT FINDINGS: We review the recent literature on glutamatergic theory, covering assessment and genetic studies, as well as drug development in animals and humans. SUMMARY: Although evidence continues to accumulate in support of glutamate hypotheses, further research continues to be required and interactions with other key systems need to be explored. PMID- 22297719 TI - An osteosarcoma zebrafish model implicates Mmp-19 and Ets-1 as well as reduced host immune response in angiogenesis and migration. AB - About 40% of osteosarcoma patients die of metastases. Novel strategies to improve treatment of metastatic patients require a better understanding of the processes involved, like angiogenesis, migration, and the immune response. However, the rarity of osteosarcoma and its heterogeneity make this neoplasm difficult to study. Recently we reported malignant transformation of mouse mesenchymal stem cells (MSCs) which formed osteosarcoma upon transplantation into mice. Here we studied these cells in zebrafish embryos and found that transformed MSCs induced angiogenesis and migrated through the bodies of the embryos, but this was never observed with non-transformed normal MSCs (progenitors of the transformed MSCs). Whole genome expression analysis of both the cells and the host showed that angiogenesis and migration-related genes matrix metalloproteinase 19 (Mmp-19) and erythroblastosis virus E26 oncogene homologue 1 (Ets-1) were overexpressed in transformed MSCs compared to normal MSCs. Investigating the host response, embryos injected with transformed MSCs showed decreased expression of immune response-related genes, especially major histocompatibility complex class 1 (mhc1ze), as compared to embryos injected with normal MSCs. These findings contribute to the identification of genetic events involved in angiogenesis, migration, and host response providing targets as well as an appropriate model for high-throughput drug screens. PMID- 22297720 TI - Mechanism of the alkali degradation of (6-4) photoproduct-containing DNA. AB - The (6-4) photoproduct is one of the major damaged bases produced by ultraviolet light in DNA. This lesion is known to be alkali-labile, and strand breaks occur at its sites when UV-irradiated DNA is treated with hot alkali. We have analyzed the product obtained by the alkali treatment of a dinucleoside monophosphate containing the (6-4) photoproduct, by HPLC, NMR spectroscopy, and mass spectrometry. We previously found that the N3-C4 bond of the 5' component was hydrolyzed by a mild alkali treatment, and the present study revealed that the following reaction was the hydrolysis of the glycosidic bond at the 3' component. The sugar moiety of this component was lost, even when a 3'-flanking nucleotide was not present. Glycosidic bond hydrolysis was also observed for a dimer and a trimer containing 5-methyl-2-pyrimidinone, which was used as an analog of the 3' component of the (6-4) photoproduct, and its mechanism was elucidated. Finally, the alkali treatment of a tetramer, d(GT(6-4)TC), yielded 2'-deoxycytidine 5' monophosphate, while 2'-deoxyguanosine 3'-monophosphate was not detected. This result demonstrated the hydrolysis of the glycosidic bond at the 3' component of the (6-4) photoproduct and the subsequent strand break by beta-elimination. It was also shown that the glycosidic bond at the 3' component of the Dewar valence isomer was more alkali-labile than that of the (6-4) photoproduct. PMID- 22297721 TI - ERIC recommendations on TP53 mutation analysis in chronic lymphocytic leukemia. AB - Recent evidence suggests that - in addition to 17p deletion - TP53 mutation is an independent prognostic factor in chronic lymphocytic leukemia (CLL). Data from retrospective analyses and prospective clinical trials show that ~5% of untreated CLL patients with treatment indication have a TP53 mutation in the absence of 17p deletion. These patients have a poor response and reduced progression-free survival and overall survival with standard treatment approaches. These data suggest that TP53 mutation testing warrants integration into current diagnostic work up of patients with CLL. There are a number of assays to detect TP53 mutations, which have respective advantages and shortcomings. Direct Sanger sequencing of exons 4-9 can be recommended as a suitable test to identify TP53 mutations for centers with limited experience with alternative screening methods. Recommendations are provided on standard operating procedures, quality control, reporting and interpretation. Patients with treatment indications should be investigated for TP53 mutations in addition to the work-up recommended by the International workshop on CLL guidelines. Patients with TP53 mutation may be considered for allogeneic stem cell transplantation in first remission. Alemtuzumab-based regimens can yield a substantial proportion of complete responses, although of short duration. Ideally, patients should be treated within clinical trials exploring new therapeutic agents. PMID- 22297722 TI - Newly diagnosed acute lymphoblastic leukemia in China (II): prognosis related to genetic abnormalities in a series of 1091 cases. AB - The molecular characterization of cytogenetic abnormalities has not only provided insights into the mechanisms of leukemogenesis but also led to the establishment of new treatment strategies targeting these abnormalities and thereby further improve the prognosis of patients. We analyzed the prognosis of 1091 Chinese patients with newly diagnosed acute lymphoblastic leukemia (ALL) and explored the prognostic impacts of a large number of cytogenetic/molecular abnormalities. It was demonstrated that, in both B- and T-ALL settings, the prognosis was negatively correlated to the age as reported to date. For childhood T-ALL patients, it was also documented that the HOX11 expression represented a favorable prognostic factor as it was in adult ones. We identified CRLF2 overexpression as an intermediate-risk marker and Ik6 variant of IKZF1 gene as a high-risk one when stratifying pediatric B-ALL cases according to cytogenetic/molecular risks. We also found that Ik6 variant and CRLF2 overexpression had an important role in dictating the prognosis of Ph-negative patients, which may be useful markers in guiding the treatment of ALL in the future, with tyrosine kinase inhibitors on the other hand reversing the fate of Ph-positive ALL patients. PMID- 22297723 TI - Role of intracellular tyrosines in activating KIT-induced myeloproliferative disease. AB - Gain-of-function mutations in KIT receptor in humans are associated with gastrointestinal stromal tumors, systemic mastocytosis and acute myelogenous leukemia. The intracellular signals that contribute to oncogenic KIT-induced myeloproliferative disease (MPD) are poorly understood. Here, we show that oncogenic KITD814V-induced MPD occurs in the absence of ligand stimulation. The intracellular tyrosine residues are important for KITD814V-induced MPD, albeit to varying degrees. Among the seven intracellular tyrosines examined, tyrosine 719 alone has a unique role in regulating KITD814V-induced proliferation and survival in vitro, and MPD in vivo. Importantly, the extent to which AKT, extracellular signal-regulated kinase and Stat5 signaling pathways are activated via the seven intracellular tyrosines in KITD814V impacts the latency of MPD and severity of the disease. Our results identify critical signaling molecules involved in regulating KITD814V-induced MPD, which might be useful for developing novel therapeutic targets for hematologic malignancies involving this mutation. PMID- 22297724 TI - Sensitivity of Eisenia andrei (Annelida, Oligochaeta) to a commercial formulation of abamectin in avoidance tests with artificial substrate and natural soil under tropical conditions. AB - Obtaining ecotoxicological data on pesticides in tropical regions is imperative for performing more realistic risk analysis, and avoidance tests have been proposed as a useful, fast and cost-effective tool. Therefore, the present study aimed to evaluate the avoidance behavior of Eisenia andrei to a formulated product, Vertimec(r) 18 EC (a.i abamectin), in tests performed on a reference tropical artificial soil (TAS), to derive ecotoxicological data on tropical conditions, and a natural soil (NS), simulating crop field conditions. In TAS tests an adaptation of the substrate recommended by OECD and ISO protocols was used, with residues of coconut fiber as a source of organic matter. Concentrations of the pesticide on TAS test ranged from 0 to 7 mg abamectin/kg (dry weight-d.w.). In NS tests, earthworms were exposed to samples of soils sprayed in situ with: 0.9 L of Vertimec(r) 18 EC/ha (RD); twice as much this dosage (2RD); and distilled water (Control), respectively, and to 2RD: control dilutions (12.5, 25, 50, 75%). All tests were performed under 25 +/- 2 degrees C, to simulate tropical conditions, and a 12hL:12hD photoperiod. The organisms avoided contaminated TAS for an EC(50,48h) = 3.918 mg/kg soil d.w., LOEC = 1.75 mg/kg soil d.w. and NOEC = 0.85 mg/kg soil d.w. No significant avoidance response occurred for any NS test. Abamectin concentrations in NS were rather lower than EC(50, 48h) and LOEC determined in TAS tests. The results obtained contribute to overcome a lack of ecotoxicological data on pesticides under tropical conditions, but more tests with different soil invertebrates are needed to improve pesticides risk analysis. PMID- 22297725 TI - Induced preference for axial chirality in a triarylmethylium o,o-dimer upon complexation with natural gamma-cyclodextrin: strong ECD signaling and fixation of supramolecular chirality to molecular chirality. AB - The ratio of the easily interconverting rotational isomers of biphenyl-2,2' diylbis[bis(4-dimethylaminophenyl)methylium] (R)/(S)-1a(2+) can be biased to prefer an R configuration upon 1:1 complexation with gamma-cyclodextrin in water. Through the reaction with Na(2)S, the preference of 1a(2+)@gamma-CyD for an axial chirality of R can be fixed as the M-helicity of dihydrothiepin 2. PMID- 22297726 TI - Coffee component 3-caffeoylquinic acid increases antioxidant capacity but not polyphenol content in experimental cerebral infarction. AB - Although coffee has antioxidant capacity, it is not known which of its bioactive compounds is responsible for it, nor has it been analyzed in experimental cerebral infarction. We studied the effect one of its compounds, 3-caffeoylquinic acid (3-CQA), at doses of 4, 25 and 100 MUg on plasma antioxidant capacity and plasma polyphenol content, measuring the differences before and after inducing a cerebral infarction in an experimental rat model. We compared them with 3 caffeoylquinic-free controls. The increase in total antioxidant capacity was only higher than in controls in 3-CQA treated animals with the highest dose. This increase in antioxidant capacity was not due to an increase in polyphenols. No differences between the experimental and control group were found regarding polyphenol content and cerebral infarction volume. In conclusion, this increase in antioxidant capacity in the group that received the highest dose of 3-CQA was not able to reduce experimental cerebral infarction. PMID- 22297727 TI - [Hospital food: new standard for higher quality]. PMID- 22297728 TI - Correction to DFT interaction energies by an empirical dispersion term valid for a range of intermolecular distances. AB - The computation of intermolecular interaction energies via commonly used density functionals is hindered by their inaccurate inclusion of medium and long range dispersion interactions. Practical computation of inter- and intra macrobiomolecule interaction energies, in particular, requires a fairly accurate yet not overly expensive methodology. It is also desirable to compute intermolecular energies not only at their equilibrium (lowest energy) configurations but also over a range of biophysically relevant distances. We present a method to compute intermolecular interaction energies by including an empirical correction for dispersion which is valid over a range of intermolecular distances. This is achieved by optimizing parameters that moderate the empirical correction by explicit comparison of density functional (B3LYP) energies with distance-dependent (DD) reference values obtained at the CCSD(T)/CBS limit. The resulting method, hereafter referred to as B3LYP-DD, yields interaction energies with an accuracy generally better than 1 kcal mol(-1) for different types of noncovalent complexes, over a range of intermolecular distances and interaction strengths, relative to the expensive CCSD(T)/CBS standard. For a training set of dispersion interacting complexes, B3LYP-DD interaction energies in combination with diffuse functions display absolute errors equal to or smaller than 0.68 kcal mol(-1). The empirical correction does not significantly increase the computational cost as compared to standard density functional calculations. Applications relevant to biomolecular energy and structure, such as prediction of DNA base-pair interactions, are also presented. PMID- 22297729 TI - Real-time fMRI biofeedback targeting the orbitofrontal cortex for contamination anxiety. AB - We present a method for training subjects to control activity in a region of their orbitofrontal cortex associated with contamination anxiety using biofeedback of real-time functional magnetic resonance imaging (rt-fMRI) data. Increased activity of this region is seen in relationship with contamination anxiety both in control subjects and in individuals with obsessive-compulsive disorder (OCD), a relatively common and often debilitating psychiatric disorder involving contamination anxiety. Although many brain regions have been implicated in OCD, abnormality in the orbitofrontal cortex (OFC) is one of the most consistent findings. Furthermore, hyperactivity in the OFC has been found to correlate with OCD symptom severity and decreases in hyperactivity in this region have been reported to correlate with decreased symptom severity. Therefore, the ability to control this brain area may translate into clinical improvements in obsessive-compulsive symptoms including contamination anxiety. Biofeedback of rt fMRI data is a new technique in which the temporal pattern of activity in a specific region (or associated with a specific distributed pattern of brain activity) in a subject's brain is provided as a feedback signal to the subject. Recent reports indicate that people are able to develop control over the activity of specific brain areas when provided with rt-fMRI biofeedback. In particular, several studies using this technique to target brain areas involved in emotion processing have reported success in training subjects to control these regions. In several cases, rt-fMRI biofeedback training has been reported to induce cognitive, emotional, or clinical changes in subjects. Here we illustrate this technique as applied to the treatment of contamination anxiety in healthy subjects. This biofeedback intervention will be a valuable basic research tool: it allows researchers to perturb brain function, measure the resulting changes in brain dynamics and relate those to changes in contamination anxiety or other behavioral measures. In addition, the establishment of this method serves as a first step towards the investigation of fMRI-based biofeedback as a therapeutic intervention for OCD. Given that approximately a quarter of patients with OCD receive little benefit from the currently available forms of treatment, and that those who do benefit rarely recover completely, new approaches for treating this population are urgently needed. PMID- 22297732 TI - Bone mineral density by DXA and HR pQCT can discriminate fracture status in men and women with stages 3 to 5 chronic kidney disease. AB - Fractures are common in chronic kidney disease (CKD). We determined if bone mineral density testing by dual energy X-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HR pQCT) could discriminate fracture status in CKD patients. Both tests were able to discriminate fracture status. Further, the addition of HR pQCT measurements to DXA measurements did not improve fracture discrimination. INTRODUCTION: The optimal method to identify individuals with CKD at high fracture risk is unknown. METHODS: We determined if bone mineral density (BMD) by DXA and HR pQCT could discriminate fracture status in 211 adult men and women with stages 3 to 5 CKD, attending predialysis clinics in Toronto Canada, using logistic regression. Results are expressed as the odds ratio (OR) of fracture (prevalent vertebral and/or low trauma since age 40 years) per standard deviation decrease in the predictor adjusted for age, weight, sex, and CKD stage. We constructed receiver operating characteristic curves to examine the discriminative ability of BMD measures for fracture. RESULTS: Most participants were Caucasian men with a mean age of 63.3 +/- 15.5 years. There were 77 fractures in 74 participants. Decreases in BMD were associated with increased fracture risk: OR = 1.56 (95% confidence interval (CI), 1.41 to 1.71) for BMD by DXA at the ultradistal radius, and OR = 1.24 (95% CI, 1.12 to 1.36) for cortical area by HR pQCT. Further, while both tests were able to discriminate fracture status, the addition of HR pQCT measures to BMD by DXA did not improve fracture discrimination ability. CONCLUSIONS: Among CKD patients not yet requiring renal replacement therapy, BMD by DXA is able to discriminate fracture status. PMID- 22297733 TI - The use of intravenous bisphosphonate therapy to treat vertebral fractures due to osteoporosis among boys with Duchenne muscular dystrophy. AB - The impact of intravenous bisphosphonate treatment to treat painful vertebral fractures in boys with DMD has not been documented. In this retrospective observational study of seven boys, 2 years of intravenous bisphosphonate therapy was associated with back pain improvement and stabilization or increases in the height ratios of fractured vertebrae. INTRODUCTION: Boys with Duchenne muscular dystrophy (DMD) are at risk for vertebral fractures. We studied the impact of intravenous bisphosphonate therapy for the treatment of painful vertebral fractures in DMD. METHODS: This was a retrospective observational study in seven boys with DMD (median 11.6 years, range 8.5 to 14.3) treated with intravenous pamidronate (9 mg/kg/year) or zoledronic acid (0.1 mg/kg/year) for painful vertebral fractures. RESULTS: At baseline, 27 vertebral fractures were evident in the seven boys. After 2 years of bisphosphonate therapy, 17 of the fractures had an increase in the most severely affected vertebral height ratio, 10 vertebrae stabilized, and none showed a decrease in height ratio. Back pain resolved completely (N = 3) or improved (N = 4). The median change in lumbar spine volumetric bone mineral density Z-score was 0.5 standard deviations (interquartile range, -0.3 to 1.7). Two boys had three incident vertebral fractures in previously normal vertebral bodies that developed over the observation period. There was a decline in the trabecular bone formation rate on trans-iliac bone biopsy but no evidence of osteomalacia. First-dose side effects included fever and malaise (N = 4), hypocalcemia (N = 2), and vomiting (N = 1); there were no side effects with subsequent infusions. CONCLUSIONS: Intravenous bisphosphonate therapy was associated with improvements in back pain and stabilization to improvement in vertebral height ratios of previously fractured vertebral bodies. At the same time, such therapy does not appear to completely prevent the development of new vertebral fractures in this context. PMID- 22297734 TI - Delay from fracture to hospital admission: a new risk factor for hip fracture mortality? AB - The relationship between surgical timing and hip fracture mortality is unknown in the context of developing countries where large delays to surgery are common. We observed that delay from fracture to hospital admission is associated with decreased survival after a hip fracture. INTRODUCTION: To examine the relationship between the time interval from fracture to surgery as well as its subcomponents (time from fracture to hospital admission and time from admission to surgery) and hip fracture survival. METHODS: The medical records of all patients aged 60 years and older admitted to a public university hospital in the city of Rio de Janeiro with a primary diagnosis of hip fracture between 1995 and 2000 were reviewed. Survival to hospital discharge and at 1 year were examined. RESULTS: Among 343 patients included in the study, there were 18 (5.3%) in hospital deaths, and 297 (86.6%) patients remained alive 1 year after surgery. Very long delays from the time of fracture to hospital admission (mean 3 days) and from hospital admission to surgery (mean 13 days) were identified. Increased time from fracture to hospital admission was associated with reduced survival to hospital discharge (hazard ratio [HR] 1.09, 95% CI 1.03-1.15, p = 0.005) and reduced survival at 1 year after surgery (HR 1.07, 95% CI 1.03-1.10, p < 0.001). The interval of time from hospital admission to surgery was not associated with reduced survival to hospital discharge (HR 1.03, 95% CI 0.96-1.10, p = 0.379) or at 1 year after surgery (HR 1.03, 95% CI 0.99-1.07, p= 0.185). CONCLUSIONS: If the association estimated in our study is causal, our results provide evidence that some hip fracture-related deaths could be prevented by improved patient access to appropriate and timely hospital care in the context of a developing country. PMID- 22297735 TI - Antiviral function and efficacy of polyvalent immunoglobulin products against CMV isolates in different human cell lines. AB - Primary infection and reactivation of human cytomegalovirus (CMV) remain a major problem in immunocompromised patients, frequently resulting in a life threatening CMV disease. Intravenous polyvalent (hyper)-immunoglobulins (IVIG) can be administered for therapy and prophylaxis of CMV infections. However, only limited data about the efficacy and mechanism of action of IVIG products against viral infections in vitro are available so far. In this study, the effect of IVIG on CMV infection in vitro was investigated using isolates from CMV-infected patients as well as the laboratory strains AD169 and TB40. A qualitative and quantitative comparison of five different commercially available IVIG products in different human cell lines was performed concerning their ability (1) to neutralize cell free virus, (2) to inhibit cell-to-cell spread and cell-associated transmission and (3) to influence CMV mRNA levels. All IVIG tested exhibited a high neutralization activity in epithelial and endothelial cell cultures (50% inhibition dose <0.1 mg/ml). However, qualitative differences between the products could be demonstrated in neutralization tests using human embryonal lung fibroblasts (HELF). The IVIG products also significantly differed in their ability to inhibit cell-to-cell spread within an CMV-infected HELF monolayer displaying inhibition rates that varied between 61 and 100%. No correlation between the ability to neutralize cell-free virus and to inhibit cell-to-cell spread could be observed. The incubation with IVIG influenced the amount of CMV immediate early and late mRNA, as indicated by a significant reduction in CMV mRNA in infected epithelial cells after incubation with IVIG in a dose-dependent manner. This study suggests different antiviral functions of polyvalent IVIG and confirms their potential to inhibit a CMV infection in vitro, with profound differences between the hereby used IVIG products. PMID- 22297736 TI - Toward improved selectivity of targeted delivery: the potential of magnetic nanoparticles. AB - Magnetic nanoparticles, mostly iron oxide-based nanoparticles, have long been used as contrasting agents in magnetic resonance imaging (MRI) applications, heat mediators in hyperthermia treatments and carriers for targeted drug delivery. Magnetic nanoparticles offer some attractive characteristics for targeted drug delivery such as drug carrying ability, nano-scale dimensions and magnetism driven selective targeting. In this issue, Escribano et al. demonstrated that iron oxide-based magnetic nanoparticles with an implanted magnet can improve selective targeting to the site of inflammation. This result opens a promising avenue for magnetic drug targeting to inflammatory diseases. PMID- 22297737 TI - Resolvins as new fascinating drug candidates for inflammatory diseases. AB - New classes of lipids such as lipoxins, resolvins, protectins and maresin are found to promote the resolution of inflammation. The resolving actions of these endogenous lipids are mediated by membrane receptors such as lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2) and cysteinyl leukotriene receptor 1 (CysLT1). Further, there exists G protein-coupled receptor 32 (GPR32), chemokine receptor-like (CMLKLR), LTB4 receptor 1 (BLT1) and unidentified high affinity surface binding receptors in human polymorphonuclear leukocytes (PMN). In particular, RX-10001 (resolvin E1) and RX-10004 (synthetic analog of resolvin, phase II) are being studied clinically in many inflammatory diseases including dry eye, retinal disease, asthma, inflammatory bowel diseases, rheumatic arthritis and cardiovascular diseases by Resolvyx Pharmaceuticals. These novel lipid classes of inflammation resolving mediators might offers new opportunities for candidates of drugs modulating chronic inflammatory diseases. Here, the progress of resolvins as new drug candidates is introduced and research on the resolution phase of inflammation is emphasized. PMID- 22297738 TI - Bioactivity-guided fractionation and analysis of compounds with anti-influenza virus activity from Gardenia jasminoides Ellis. AB - Bioassay-guided fractionation of extracts from Fructus Gardeniae led to analysis of its bioactive natural products. After infection by influenza virus strain A/FM/1/47-MA in vivo, antiviral activity of the extracts were investigated. The target fraction was orally administered to rats and blood was collected. High performance liquid chromatography coupled with photo diode array detector and electrospray ion trap multiple-stage tandem mass spectrometry was applied to screen the compounds absorbed into the blood. A structural characterization based on the retention time, ultraviolet spectra, parent ions and fragmentation ions was performed. Thirteen compounds were confirmed or tentatively identified. This provides an accurate profile of the composition of bioactive compounds responsible for the anti-influenza properties. PMID- 22297739 TI - Cytotoxic oleane-type triterpene saponins from Glochidion eriocarpum. AB - The anticancer activity of ten compounds from the aerial parts of Glochidion eriocarpum were evaluated on two human cancer cell lines, HL-60 and HCT-116. Compounds 1-4 displayed highly potent cytotoxic activity on the HCT-116 cancer cell line with IC(50) values ranging of 0.41~1.16 MUM. Compounds 1-4 significantly inhibited the HL-60 cell line with IC(50) values ranging of 4.51~6.33 MUM. These results suggested that the benzoyl group at the C-22 position in oleane-type triterpene saponins was essential for cytotoxicity towards tumor cells. Moreover, compounds 2 and 3 showed more potent cytotoxicity than compounds 1 and 4 against HL-60 and HCT-116 cells. With respect to the mechanism underlying cytotoxicity, compounds 1-4 increased chromatin condensation, a typical apoptotic characteristic in HL-60 and HCT-116 cells. In the mechanism of apoptosis induction, compounds 1-4 reduced Bcl-2 expression, whereas the expression of Bax was increased compared to controls in HCT-116 cells. In addition, compounds 1-4 decreased the level of procaspase-3. The cleavage of poly (ADP-ribose) polymerase (PARP), a vital substrate of effector caspase, was observed in HCT-116 cells. Furthermore, the induction of apoptosis was also accompanied by an activation of extracellular signal-regulated kinase (ERK) and p38 kinase in HCT-116 cells. These findings provide evidence demonstrating that the pro-apoptotic effects of compounds 1-4 are mediated through the activation of ERK and p38 in HCT-116 cells. PMID- 22297740 TI - Antitrypanosomal activities and cytotoxicity of some novel imido-substituted 1,4 naphthoquinone derivatives. AB - The antitrypanosomal activities, cytotoxicity, and selectivity indices of eleven imido-substituted 1,4-naphthoquinone derivatives and nifurtimox have been studied. Compared to nifurtimox (IC(50) = 10.67 MUM), all the imido naphthoquinone analogs (IMDNQ1-IMDNQ11) are more potent on Trypanosoma cruzi with IC50 values ranging from 0.7 MUM to 6.1 MUM (p < 0.05). Studies of the cytotoxic activities of these compounds on a Balb/C 3T3 mouse fibroblast cell line revealed that four of these compounds, IMDNQ1, IMDNQ2, IMDNQ3, and IMDNQ10 displayed selectivity indices of 60.25, 53.97, 31.83, and 275.3, respectively, rendering them significantly (p < 0.05) more selective in inhibiting the parasite growth than nifurtimox (selectivity index = 10.86). PMID- 22297741 TI - 3,5-disubstituted thiadiazine-2-thiones: new cell-cycle inhibitors. AB - Two series, a and b, of 3-cyclopentyl or (3-cyclohexyl)-5-substituted-3,4,5,6 tetrahydro-2H-1,3,5-thiadiazine-2-thiones (THTT) 2a-9a and 3b, 4b, 6b-9b, were synthesized to develop new cell cycle inhibitors. Variable and promising in vitro antiproliferative activities were shown with the synthesized THTT derivatives. Compound 5a with a 5-cyclopentyl group on position-3 and a glutamine residue on position-5 of the THTT moiety showed maximum activity (IC(50) = 8.98 MUM). Compound 5a possessed notable cell cycle disrupting and apoptotic activities with enhanced selectivity against cancer cells, suggesting the potential for the development of new selective cell cycle inhibitors. There is no evident relationship between the cytotoxic activity of the tested compounds and their lipophilicity. In addition, a pharmacophore based study was performed to explain the biological activity on structural bases. A successful model was generated with a good correlation with the observed activity. PMID- 22297742 TI - Synthesis and in vitro antiproliferative activity of 2-methyl-3-(2-piperazin-1-yl ethyl)-pyrido[1,2-a]pyrimidin-4-one derivatives against human cancer cell lines. AB - A series of new 2-methyl-3-(2-piperazin-1-yl-ethyl)-pyrido[1,2-a]pyrimidin-4-one derivatives 6a-j were synthesized by a nucleophilic substitution reaction of 2 methyl-3-(2-piperazin-1-ylethyl)-pyrido[1,2-a]pyrimidin-4-one with various sulfonyl chlorides. The compounds were characterized by different spectral studies. All the compounds were evaluated for their antiproliferative effect using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay method against four human cancer cell lines (K562, Colo-205, MDA-MB 231, IMR-32) for the time period of 24 h. Among the series, compounds 6d, 6e and 6i showed good activity on all cell lines except K562, whereas the other compounds in the series exhibited moderate activity. Compound 6d could be a potential anticancer agent and therefore deserves further research. PMID- 22297743 TI - Novel 4-(4-substituted-thiazol-2-ylamino)-N-(pyridin-2-yl)-benzenesulfonamides as cytotoxic and radiosensitizing agents. AB - A series of novel 4-(4-substituted-thiazol-2-ylamino)-N-(pyridin-2-yl) benzene sulfonamides were synthesized and screened for their cytotoxic activity against human breast cancer cell line (MCF-7). Compounds 6, 7, 9, 10, 11, and 14 displayed significant activity against MCF-7 when compared to doxorubicin, which was used as a reference drug. The synergistic effect of Gamma radiation for the most active derivatives 7, 9, and 11 was also studied and their IC(50) values markedly decreased to 11.9 MUM, 11.7 MUM, and 11.6 MUM, respectively. PMID- 22297744 TI - Life span extension of Caenorhabditis elegans by novel pyridoperimidine derivative. AB - Zwitterions formed from the addition of triphenylphosphine to dialky acetylene dicarboxylates attack the nucleus of both 1H-perimidine (1) and 1H benzo[d]imidazole (9) to form novel pyrido[1,2,3-cd]perimidine and imidazo[4,5,1 ij]quinoline derivatives in moderate yields (64-72%). The biological activity of the products has been studied. Compound 3a was found to extend life span of wild type Caenorhabditis elegans under standard laboratory conditions. Both heat stress and induced chemical stress resistance of wild type C. elegans were improved in a reverse dose-dependent manner due to 3a treatment. In addition, treatment of worms with compound 3a significantly attenuated the formation of advanced glycation end products in a reverse dose-dependent manner. PMID- 22297745 TI - Synthesis and antiviral evaluation of 7-O-arylmethylquercetin derivatives against SARS-associated coronavirus (SCV) and hepatitis C virus (HCV). AB - Aryl diketoacid (ADK) is well known for antiviral activity which can be enhanced by introduction of an aromatic arylmethyl substituent. A natural flavonoid quercetin has a 3,5-dihydroxychromone pharmacophore which is in bioisosteric relationship with the 1,3-diketoacid moiety of the ADK. Thus, it was of our interest to test the antiviral activity of the quercetin derivatives with an arylmethyl group attached. In this study, we prepared a series of the 7-O arylmethylquercetin derivatives with various aromatic substituents and evaluated their antiviral activity against the SARS-associated coronavirus (SARS-CoV, SCV) as well as hepatitis C virus (HCV). Single difference in the aromatic substituent fine-tuned the biological activity of the 7-O-arylmethylquercetin derivatives to result in two different classes of derivatives selectively active against SCV and HCV. PMID- 22297746 TI - Constituents from the stem barks of Canarium bengalense with cytoprotective activity against hydrogen peroxide-induced hepatotoxicity. AB - Phytochemical investigation of the stem barks of Canarium bengalense (Burseraceace) resulted in the isolation of a new flavone glycoside (5) together with six known compounds (1-4, 6, and 7). The chemical structure of the new compound was elucidated as 3'-hydroxy-7,4'-dimethoxyflavone-5-O-alpha-L arabinofuranosyl-(1->6)-beta-D-glucopyranoside by means of 1D and 2D NMR ((1)H (1)H COSY, HMQC, and HMBC) and MS analyses. To evaluate the in vitro cytoprotective effect, the isolates (1-7) were tested against hydrogen peroxide (H(2)O(2))-induced damage in primary cultured hepatocytes. The viability of hepatocytes was increased by treatment with each compound, except compound 1. Compounds 3, 4, and 7 exerted cytoprotective effects comparable to curcumin, the positive control. Our results suggest that the cytoprotective constituents of C. bengalense may contribute to its traditional use in the treatment of tumor and liver damage. PMID- 22297747 TI - Effect of magnet implant on iron biodistribution of Fe@C nanoparticles in the mouse. AB - The in vivo biodistribution of Fe@C nanoparticles (NP) was tested in mice bearing an inflammatory focus induced by injecting carrageenan into an air pouch previously formed on their back. The animals were intravenously injected NP with a high (60 mg/kg) or a low iron dose (6 mg/kg) and sacrificed 2 h later. Blood and organ samples (liver, spleen, lung, and kidney) were obtained; washed exudates were also collected. Iron concentration in plasma, blood cells, organs, and exudates was determined by flameless atomic-absorption-spectroscopy after digestion of organic material. Pouch exudate volume increased in all groups of mice with experimental inflammation. After i.v. administration of the high and low dose of NP, iron in exudate increased by 83.3% and 92.2%, respectively. A similar increase in hepatic iron appeared after the high dose (78%), but no increase appeared after the low dose. When the magnet was present, a 157% and 119% increase of iron in exudate appeared after both doses of NPs, but only the high dose of NP increased iron liver (60%). The presence of a magnetic field in the pouch favored selective biodistribution of NP in the inflammatory focus. These results indicate that mice with an inflammatory compartment are suitable for primary screening of different NP types. They also show that selective biodistribution is greater when a low dose of NP was used and that distribution in the target organ was increased by the magnetic field. PMID- 22297748 TI - Determination of 5-hydroxymethyl-2-furfural, albiflorin, paeoniflorin, liquiritin, ferulic acid, nodakenin, and glycyrrhizin by HPLC-PDA, and evaluation of the cytotoxicity of Palmul-tang, a traditional Korean herbal medicine. AB - A high-performance liquid chromatographic (HPLC) method was developed for quantitative analysis of seven components, 5-hydroxymethyl-2-furaldehyde (1), albiflorin (2), paeoniflorin (3), liquiritin (4), ferulic acid (5), nodakenin (6), and glycyrrhizin (7) of Palmul-tang (PMT), a traditional Korean medicine. HPLC analysis was performed using a Gemini C18 column at 40 degrees C, and photodiode array (PDA) detection at 230 nm, 254 nm, 280 nm, 320 nm, and 330 nm was used for quantification of the seven components in PMT. The mobile phase was a gradient flow composed of two solvent systems. Solvent A was 1.0% (v/v) aqueous acetic acid and solvent B was acetonitrile containing 1.0% (v/v) acetic acid. Calibration curves were acquired with r (2) values > 0.9998, and the relative standard deviations (RSDs, %) for intra- and interday precision were both less than 6.0%. The recovery of each component was in the range of 90.66-103.79%, with a RSD less than 5.0%. The contents of the seven components in PMT range form 0.61 6.21 mg/g. Additionally, we investigated the cytotoxicity of the extract against the RBL-1 and BEAS-2B cell lines, as well as splenocytes. PMID- 22297749 TI - Ethosomes, binary ethosomes and transfersomes of terbinafine hydrochloride: a comparative study. AB - The aim of this study was to compare the skin permeation of ethosomes, binary ethosomes and transfersomes of Terbinafine Hydrochloride (TH) under non-occlusive conditions. These lipid vesicles were prepared and characterized for shape, size, zeta-potential and entrapment efficiency. Franz diffusion cells and confocal laser scanning microscopy (CLSM) were used for the percutaneous absorption studies. The quantity of drug in the skin from ethosomes, binary ethosomes (the weight ratio of ethanol to propylene glycol 7:3, ethanol-PG = 7:3, w/w), and transfersomes was 1.26, 1.51 (p <0.05), 1.56 (p <0.01) times higher than that of TH from traditional liposomes (control). The skin deposition of the applied dose (DD%) of TH from ethosomes, binary ethosomes, and transfersomes was 3.34 (p < 0.05), 9.88 (p < 0.01), 2.52 times higher than that of TH from control. The results of CLSM experiments showed that penetration depth and fluorescence intensity of Rhodamine B from binary ethosomes was much greater than that from ethosomes and transfersomes. These results indicated the binary ethosomes (ethanol-PG = 7:3, w/w) most effectively permitted drug penetration through skin; transfersomes made drug easiest to accumulate in the skin. Ethosomes improved drug delivery with greater improvement in skin permeation than improvement in skin deposition. PMID- 22297750 TI - Inhibitory effect of homochlorcyclizine on melanogenesis in alpha-melanocyte stimulating hormone-stimulated mouse B16 melanoma cells. AB - The histamine receptor H1 antagonist homochlorcyclizine (HC) has been widely used as an antihistamine agent for the treatment of allergies. However, the effect of HC on skin pigmentation is not known. In the present study, we investigated the inhibitory effect of HC on melanogenesis in mouse B16 melanoma cells. Our results showed that HC inhibited melanogenesis in either alpha-melanocyte stimulating hormone (alpha-MSH)- or 3-isobutyl-1-methylxanthin (IBMX)-stimulated B16 cells in a dose-dependent manner. Despite the strong inhibition of melanogenesis by HC, it was surprisingly found that HC did not reduce either cellular or melanosomal tyrosinase activity in alpha-MSH-stimulated B16 cells. In addition, HC also did not directly inhibit either murine or mushroom tyrosinase activity in the cell free system. Moreover, western blotting and reverse-transcription polymerase chain reaction (RT-PCR) analyses respectively confirmed that HC did not downregulate levels of tyrosinase protein and its mRNA in alpha-MSH-stimulated B16 cells. These results clearly demonstrated that HC inhibits melanogenesis of B16 cells by a mechanism other than reduction of the cellular tyrosinase activity. From the present study, HC was proven to be a good candidate as a skin whitening agent for treatment of skin hyperpigmentation, and this generic drug might be suitable for use in combination with other depigmenting agents due to its unique inhibition mechanism. PMID- 22297751 TI - Monocytic differentiation of K562 cells induced by proanthocyanidins from grape seeds. AB - Grape seeds procyanidins can inhibit the proliferation of some cancer cell lines and have strong antioxidant activity. The purpose of this study was to investigate whether grape seeds procyanidins affect the proliferation and redifferentiation in K562 cells. The sulforhodamine B colorimetric assay and trypan blue staining were used to measure cell proliferation and survival. Morphological changes, NBT reductive activity, and surface antigens were used to detect redifferentiation of K562 cells. Intracellular reactive oxygen species (iROS) were detected by a fluorescent probe. Grape seeds procyanidins inhibited cell proliferation but the treatment did not appreciably increase lethality. After treatment with grape seeds procyanidins, a typical differentiated morphology was observed. The positive rate of CD11b and CD14 cells and NBT reductive activities increased significantly. As antioxidants, grape seeds procyanidins can induce arrest in the phase G1 and decrease iROS formation. All results indicate that the antioxidant grape seeds procyanidins are likely to induce monocytic differentiation in leukemia cells, mostly through decreasing iROS formation and inducing phase G1 arrest. PMID- 22297752 TI - The effect of isolancifolide on the apoptosis in HL-60 cells through caspase-8 dependent and -independent pathways. AB - Isolancifolide is a compound extracted and isolated from Actinodaphne lancifolia, which is a traditional oriental medicine. To determine whether isolancifolide has therapeutic potential as an anticancer molecule, we assessed its apoptotic effects on HL-60 cells, a human leukemia cell line. Apoptotic activities were investigated using DNA fragmentation assay, immunoblotting, and flow cytometry. We found that the inhibitory concentration 50% of isolancifolide was approximately 20 M. The time- and dose-dependent effects of isolancifolide on apoptosis were determined by DNA fragmentation and propidium iodide staining, and the involvement of caspases and the Bcl-2 family in isolancifolide-induced apoptosis was assessed by Western blotting. During exposure to isolancifolide, the pro-forms or full length of caspases-8, -3, and Bid were decreased, as assessed by Western blotting, while the levels of cleaved forms of caspases-8, 3, and PARP were increased. We observed that the release of cytochrome c and Smac/DIABLO from the mitochondria to the cytosol was accompanied by the loss of mitochondrial membrane potential. The caspase specific inhibitors, z-IETD-fmk and z-LEHD-fmk, blocked the accumulation of sub-G1 cells and the release of cytochrome c, but not that of Smac/DIABLO. These results indicate that isolancifolide induces apoptosis of HL-60 cells through both death receptor and mitochondria pathways, in caspase-8-dependent and -independent manners, suggesting that isolancifolide may be useful in anticancer strategies. PMID- 22297753 TI - Protective effects of acetyl-L-carnitine on neurodegenarative changes in chronic cerebral ischemia models and learning-memory impairment in aged rats. AB - This study investigated the effects of acetyl-L-carnitine (ALC) in secondarily induced cerebral chronic ischemia models using rats with permanent ligation of bilateral common carotid arteries (BCCL) and spontaneously hypertensive rats (SHR). Additionally, we used normal aged rats as a primary dementia model. Chronic ALC administration at 100 mg/kg (p.o.) for 4 weeks significantly attenuated neurodegenerative changes. In groups receiving 50 mg/kg or 100 mg/kg, ALC inhibited the active astrocyte increase in cerebral tissues of both BCCL and SHR models. In BCCL rats, ALC administration (50 mg/kg or 100 mg/kg, p.o.) resulted in significant promotion of glutathione levels in brain tissues. We also confirmed behavioral improvement after ALC treatment (100 mg/kg for 8 weeks, p.o.) on learning-memory function using aged rats (18 months old) in a passive avoidance task and preservation of CA1 pyramidal neurons was coincided on histopathological observation. In conclusion, chronic ALC administration may ameliorate cerebral ischemia progress after a cerebrovascular disorder as well as spontaneous ageing-related cerebral dysfunction via hippocampal protection. PMID- 22297754 TI - Anti-inflammatory effect of atorvastatin on vascular reactivity and insulin resistance in fructose fed rats. AB - We investigated the possible protective effect of atorvastatin against vascular dysfunction associated with insulin resistance (IR) in fructose-fed model rats. The effect of atorvastatin (10 mg/kg/day for 8 weeks) on vascular reactivity, glucose, cholesterol, insulin, and the IR index in a well-established model of dietary hypertriglyceridemia, the fructose-fed rat, was investigated. Fructose feeding (10% fructose in drinking water for 8 weeks) induced hypercholesterolemia and hyperinsulinemia without any change in blood glucose levels. Fructose feeding also elevated serum tumor necrosis factor-alpha (TNF-alpha), the insulin resistance index, leukocyte infiltration, and endothelial cell pyknosis. Fructose feeding induced hyper-responsiveness to both phenylephrine (PE), KCl, and hyporesponsiveness to acetylcholine (Ach) but not to sodium nitroprusside-induced relaxation. Atorvastatin, given concurrently with fructose, reduced hypercholesterolemia, hyperinsulinemia, TNF-alpha level, and the IR index. It also reduced leukocyte infiltration and endothelial cell pyknosis and decreased hyper-responsiveness to both PE and KCl but did not affect hyporesponsiveness to Ach relaxation. In conclusion, atorvastatin protected against impairment in aortic vascular reactivity associated with insulin resistance, particularly increased contractility, but not reduced endothelium-dependent relaxation, by a mechanism involving a reduction in cholesterol and IR in addition to anti inflammatory effects. PMID- 22297755 TI - Protection of prenylated flavonoids from Mori Cortex Radicis (Moraceae) against nitric oxide-induced cell death in neuroblastoma SH-SY5Y cells. AB - Seven prenylated flavanoids, licoflavone C (1), cyclomulberrin (2), neocyclomorusin (3), sanggenon I (4), morusin (5), kuwanon U (6) and kuwanon E (7), and three 2-arylbenzofurans, moracin P (8), moracin O (9), and mulberrofuran Q (10) were isolated from the MeOH extract of Mori Cortex Radicis. Among these, compounds 2-7 enhanced cell viability in a dose-dependent manner against sodium nitroprusside-induced cell death in neuroblastoma SH-SY5Y cells, which was measured by MTT reduction assay (EC(50) values of 4.4, 5.6, 8.0, 6.4, 8.7, and 11.9 MUg/mL, respectively). Among 10 compounds, C-3 prenylated flavones (2, 3, and 5) and prenylated flavanones (4, 6, and 7) showed cell protection. However, compound 1 which lacks the prenyl group at C-3 and three 2-arylbenzofurans (8-10) did not show protective effect. The order of cell protection was as follow: C-3 prenylated flavones (2, 3, and 5) > prenylated flavanones (4, 6, and 7) > 2 arylbenzofurans (8-10) and flavone (1). From this result, we show that some prenylated flavones and flavanones might protect neuronal cells against nitrosative stress-mediated cell death. Even though further evaluations are necessary in vitro and in vivo study, we carefully suggest that some prenylated flavonoids from Mori Cortex Radicis might protect neuronal cells from neurodegenerative diseases. PMID- 22297756 TI - Protective effect of [6]-gingerol on the ethanol-induced teratogenesis of cultured mouse embryos. AB - Excessive ethanol consumption during pregnancy causes fetal alcohol syndrome. We investigated the effect of [6]-gingerol on ethanol-induced embryotoxicity using a whole embryo culture system. The morphological changes of embryos and the gene expression patterns of the antioxidant enzymes cytosolic glutathione peroxidase (cGPx), cytoplasmic Cu/Zn superoxide dismutase (SOD1), and Mn-SOD (SOD2), and SOD activity were examined in the cultured mouse embryos exposed to ethanol (5 MUL/3 mL) and/or [6]-gingerol (1*10(-8) or 1*10(-7) MUg/mL) for 2 days. In ethanol exposed embryos, the standard morphological score of embryos was significantly decreased compared with those of the control (vehicle) group. However, cotreatment of embryos with [6]-gingerol and ethanol significantly improved all of the developmental parameters except crownrump length and head length, compared with those of the ethanol alone group. The mRNA expression levels of cGPx and SOD2, not SOD1, were decreased consistently, SOD activity were significantly decreased compared with the control group. However, the decreases in mRNA levels of antioxidant enzymes and SOD activity were significantly restored to the control levels by [6]-gingerol supplement. These results indicate that [6] gingerol has a protective effect against ethanol-induced teratogenicity during mouse embryogenesis. PMID- 22297757 TI - In vitro antioxidant and anti-inflammatory activities of Angelica decursiva. AB - Mounting evidences continue to support the involvement of oxidative/nitrosative stress and inflammation in the pathogenesis of many diseases. Plant constituents having antioxidant activities together with anti-inflammatory activities may provide better opportunities to develop anti-inflammatory agents. In view of this, we evaluated the antioxidant and antiinflammatory activities of methanolic extract of whole plants of Angelica decursiva, and its solvent soluble fractions via in vitro activities against lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 cells, as well as in vitro scavenging activities against 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid, NO, and peroxynitrite. Among the tested fractions, the ethyl acetate fraction was found as the most active antioxidant fraction together with significant anti-inflammatory effect. From the active ethyl acetate fraction, four coumarin derivatives consisting of nodakenin, nodakenetin, umbelliferone, and umbelliferone-6-carboxylic acid, along with a phenolic compound, vanillic acid, were isolated. Among them, umbelliferone 6-carboxylic acid and vanillic acid were isolated for the first time from this plant. In all antioxidant assays, vanillic acid showed the highest antioxidant potential followed by umbelliferone 6-carboxylic acid among the isolated compounds. In the anti-inflammatory assay, umbelliferone 6-carboxylic acid exhibited the highest inhibitory activity against lipopolysaccharide-induced NO production in RAW 264.7 cells with an IC(50) value of 72.98 MUg/mL. Therefore, the present study reveals the potential antioxidant and antiinflammatory activities of whole plants of A. decursiva and its constituents, mainly umbelliferone 6-carboxylic acid, which could be used in the development of therapeutic and preventive agents for oxidative stress-related inflammatory diseases. PMID- 22297758 TI - Venlafaxine: the yin and yang of antidepressants? PMID- 22297759 TI - Loss of social status: preliminary evaluation of a novel animal model of depression. AB - Stable dominance hierarchies were determined in pairs of male Lister hooded rats, by repeated observation of agonistic behaviour at the onset of the dark phase of the light-dark cycle. No lasting alterations in dominance behaviour were caused by subjecting the dominant member of the pair either to restraint stress or to defeat by another dominant animal. However, defeat of the dominant animal by a male of the aggressive Tryon Maze Dull (TMD) strain caused a loss of dominant status in the home cage which lasted at least 7 days. Repeated weekly defeat by TMD animals decreased both home cage dominance behaviour and consumption of a palatable sucrose solution, relative to non-defeated animals; both behaviours were normalized in defeated animals by 3 weeks of treatment with the tricyclic antidepressant imipramine. PMID- 22297760 TI - Behavioural and neuroendocrine responses to D-fenfluramine in rats treated with neurotoxic amphetamines. AB - The amphetamine derivatives p-chloroamphetamine (pCA), 3,4 methylenedioxymethamphetamine (MDMA, 'Ecstasy') and D-fenfluramine can, if given repeatedly in high doses to rats, produce a degeneration of serotonergic nerve terminals which we have previously shown to result in a reduction in D fenfluramine-evoked release of 5-HT in vivo. It is therefore possible that fenfluramine-evoked responses may have value as a probe of 5-HT neurodegeneration in man. The present study examined the effect of pre-treatment with these three agents (pCA 12 mg/kg*2; MDMA 20 mg/kg*8; D-fenfluramine 12.5 mg/kg*8, 14 days prior to testing) on behavioural (5-HT syndrome) and neuroendocrine [prolactin and adrenocorticotrophin (ACTH)] responses in rats to acute administration of D fenfluramine and other serotonergic agonists. All three pre-treatments attenuated the D-fenfluramine-evoked behavioural syndrome, but did not affect the prolactin or ACTH responses to acute challenge with D-fenfluramine (apart from a small effect of pre-treatment with pCA on the ACTH response to D-fenfluramine). For comparison, the effect of pCA pre-treatment on the behavioural responses to acute administration of pCA and the 5-HT(1A) and 5-HT(2) receptor agonists 8-hydroxy-2 (di- n- propylamino)tetralin (8-OH-DPAT) and 1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane (DOI), respectively, were also examined. pCA pre-treatment attenuated all components of the behavioural response to pCA but had little or no effect on the behavioural responses to 8-OH-DPAT or DOI, suggesting that there was no alteration in post-synaptic 5-HT(1A) or 5-HT(2) receptor function. While the loss of behavioural effect of D-fenfluramine on rats pre-treated with neurotoxic amphetamines can be understood in terms of the loss of D fenfluramine's 5-HT-releasing action following 5-HT neurodegeneration, the lack of change in the neuroendocrine responses to D-fenfluramine is not easily explicable in this way. These results emphasise the need for further research into the actions of D-fenfluramine before carrying it forward as a probe of neurodegeneration in man. PMID- 22297761 TI - Continuous exposure to FG 7142: behavioural sensitisation is not accompanied by changes in benzodiazepine/GABA receptor coupling. AB - Chronic intermittent high-dose treatment with N-methyl-beta-carboline-3 carboxamide (FG 7142) leads to kindling accompanied by reduction in gamma aminobutyric acid (GABA) receptor function, whereas chronic continuous administration may result in behavioural effects in the opposite direction from those of acute FG 7142. In the present study, we have investigated the effects of continuous administration of low doses of FG 7142 on the response to an acute challenge dose of FG 7142 in an ethologically based model of anxiety. Rats treated continuously for 14 days with FG 7142 delivered by osmotic minipump at a rate of 1.2-1.5 mg/kg/day showed sensitisation to the anxiogenic effects of a challenge dose of FG 7142 (6 mg/kg), as measured in the elevated plus-maze. This was not accompanied by any change in benzodiazepine/GABA receptor coupling, as assessed by the 'GABA shift'. These results indicate that continuous low-dose treatment with FG 7142 can elicit sensitisation to the behavioural effects of FG 7142, but that this is unlikely to be mediated by changes in benzodiazepine/GABA receptor coupling. PMID- 22297762 TI - Discriminative stimulus properties of ethoxy idazoxan. AB - The technique of drug discrimination was used to examine the ability of the highly selective alpha(2)-adrenoceptor antagonist ethoxy idazoxan, which has negligible affinity for alpha( 1)-adrenoceptors or I(2) imidazoline receptors, to produce an interoceptive discriminable stimulus or cue in rats. Rats were trained to respond on one lever after receiving alpha-ethoxy idazoxan (2.5 mg/kg, i.p.) and on the opposite lever after saline vehicle. The ethoxy idazoxan cue appeared to be mediated by antagonists of central alpha(2)-adrenoceptors, on the basis that dose- related substitution was produced by the highly selective alpha(2) adrenoceptor antagonists idazoxan (imidazoline), fluparoxan and 1-(2-pyrimidinyl) piperazine (1-PP) (both non-imidazoline) but not by clonidine, which acts as an agonist at this receptor, nor by the peripherally acting alpha(2)-adrenoceptor antagonist L659,066. However, the alpha(2)-adrenoceptor antagonists yohimbine and atipamezole showed partial and non-dose-dependent substitution for ethoxy idazoxan over a wide range of doses. 2-BFI [2-(2-benzfuranyl)-2-imidazoline, RX801077], an imidazoline which is highly selective for I(2) imidazoline receptors over alpha(2)-adrenoceptors, showed dose- dependent substitution for ethoxy idazoxan, although the maximum effect (73% responding on the ethoxy idazoxan lever) fell short of criteria adopted for full substitution. Among other agents which bind to I(2) receptors, only idazoxan and 2-phenyl-2-imidazoline exhibited significant substitution; cirazoline could only be tested at very low doses because it powerfully inhibited responding in general, probably due to its alpha(1)-adrenoceptor agonist properties. It is suggested that the ability of 2 BFI to substitute partially for ethoxy idazoxan might be due to the ability of both agents to increase extracellular concentrations of noradrenaline. PMID- 22297763 TI - 5-HT 1D receptors mediate SKF 99101H-induced hypothermia in the guinea pig. AB - The selective, brain penetrant, 5-HT(1D) receptor agonist SKF 99101H (10-30 mg/kg i.p.) caused a dose-related fall in rectal temperature in guinea pigs which lasted longer than 2 h. Sumatriptan (1.0-100 mg/kg i.p.), a selective 5-HT(1D) agonist which does not penetrate the brain, did not produce hypothermia, suggesting that peripheral mechanisms are not critically involved in the response. The hypothermia induced by SKF 99101H (30 mg/kg i.p.) was dose dependently blocked by the 5-HT(1D) receptor antagonists GR 127935 (0.01-1 mg/kg i.p.) and GR 125743 (0.01-3 mg/kg i.p.), confirming the role of 5-HT(1D) receptors. Mianserin (0.3-10.0 mg/kg i.p.) and granisetron (0.1-3.0 mg/kg i.p.) were inactive, suggesting that 5-HT(2A/2B/2C) or 5-HT( 3) receptors play no significant role in the generation of the hypothermic response. Nor was the hypothermia reversed by prazosin (0.03-1.0 mg/kg i.p.), idazoxan (0.03-1.0 mg/kg i.p.) or scopolamine (0.01-0.3 mg/kg i.p.), thereby excluding mediation by alpha(1)- and alpha(2)-adrenoceptors and muscarinic receptors. WAY 100635 (0.1 1.0 mg/kg) significantly potentiated the effect of SKF 99101H. The antagonists, when given alone, had no effect on body temperature, with the exception of prazosin (0.1 and 1.0 mg/kg). Three days of treatment with parachloroamphetamine (30 mg/kg i.p.) depleted forebrain 5-HT by ~ 75% in frontal cortex, hypothalamus, hippocampus and striatum, but failed to alter the hypothermic response to SKF 99101H. The hypothermia is, therefore, unlikely to be mediated by 5-HT(1D) receptors located on 5-HT neurons. SKF 99101H-induced hypothermia in the guinea pig may serve as a useful model for investigation of centrally acting 5-HT( 1D) receptor antagonists. PMID- 22297764 TI - Serotonergic drug effects on a delayed conditional discrimination task in the rat; involvement of the 5-HT1A receptor in working memory. AB - We investigated the effects of serotonergic drugs on working memory (WM) in a delayed conditional discrimination task. The 5-HT(1A) receptor full agonist flesinoxan (0.3-3.0 mg/kg) dose- and delay-dependently impaired performance, indicating a specific effect on WM. The 5-HT(1A) receptor partial agonist ipsapirone, the 5-HT( 1B/1D/2C) agonist TFMPP, the 5-HT(1A) antagonist NAN190 and the serotonin re-uptake inhibitor fluvoxamine dose-dependently impaired performance, in a delay-independent manner, indicating no specific effect on WM. The 5-HT( 2) receptor antagonist ketanserin and the 5-HT(3) receptor antagonist ondansetron did not affect performance. It is suggested that the role of central serotonin receptors in WM may be restricted to 5-HT(1A) receptors. PMID- 22297765 TI - Lorazepam 0.25 mg twice a day improves aspects of psychometric performance in healthy volunteers. AB - The effects of lorazepam (0.25 mg) twice a day on several cognitive and performance tasks, pictures test, digit-symbol substitution test (DSST), choice reaction time (CRT) and critical flicker fusion (CFF), were investigated in healthy students. A double-blind independent group design was used to compare placebo and lorazepam (30 volunteers in each group). After randomisation, all subjects received placebo for 3 days (D), followed by 14 days of treatment, with either lorazepam or placebo. Subjects completed a battery of tests at Do, then D(3), D(7) , D(10) and D(14). D(3) performance was poorer in the lorazepam group except for CFF (ascending values and total values), yet the only significant improvement was in total reaction time on the CRT test. However, a significant improvement of performance was shown at D(7), D(10) and D(14) in the lorazepam group compared with the control group (except in recognition reaction time). The current study shows that low repeated doses of lorazepam are able to produce small improvements in some aspects of psychomotor and cognitive functions in healthy volunteers. Different points are discussed to explain the performance improvement: training effect, tolerance effect, partial inverse agonist effect and the possible release of cholecystokinin. PMID- 22297766 TI - Critical flicker fusion threshold and anticholinergic effects of chronic antidepressant treatment in remitted depressives. AB - The persistence of deficits in cognitive performance in major depressive patients taking maintenance antidepressant medication was assessed by examining groups of patients in clinical remission, stable on one of a range of tricyclics or selective serotonin re-uptake inhibitors (SSRIs) for at least 3 months, compared with controls. Measures of critical flicker fusion (CFF), choice reaction time (CRT), subjective sedation, and anticholinergic side-effect score were made. Tricyclic antidepressants (TCAs) produce a significant deficit in critical flicker fusion threshold compared both to controls and SSRIs. Similar effects were seen with choice reaction times which were significantly affected by age. Sedation scores were significantly higher with TCAs than SSRIs. Anticholinergic side effects were strongly related to CFF, less so to visual analogue sedating scales and not significantly to CRT. The effect measured by CFF is different from sedation, and may be related to the anticholinergic potency of the drug; it may be considered a drug-induced pseudodementia. This effect represents a risk factor for accidents during maintenance therapy and may impair work and leisure performance. The relative risk of weight gain with TCAs compared to SSRIs in women was 5.92 (95% CI 1.79-19.50). PMID- 22297767 TI - A comparison of the acute effects of a low dose of alcohol on mood and performance of healthy volunteers and subjects with upper respiratory tract illnesses. AB - An experiment was carried out to determine whether a low dose of alcohol produced different behavioural effects in healthy volunteers to those suffering from an upper respiratory tract illness. Ninety-nine subjects were tested, with 48 subjects being assigned to the alcohol condition and 51 to the juice only condition. A dose of 1.5 ml of vodka per kg body weight was used and the alcohol manipulation was double-blind. Approximately half of the subjects in each condition were healthy and the others had upper respiratory tract illnesses, probably colds. Subjects with colds reported an increase in negative affect and were slower at performing psychomotor tasks. Few main effects of alcohol were obtained. Of major interest were the interactions between health status and alcohol conditions. The alcohol improved the mood of healthy subjects but produced greater negative moods in subjects with colds. Similarly, performance of selective and sustained attention tasks showed different effects of alcohol in healthy and ill subjects. PMID- 22297768 TI - Neurochemical and some related psychopharmacological aspects of Tourette's syndrome: an update. AB - Neurochemical investigations of Tourette's syndrome (TS) suggest that the symptoms of this disorder may be the result of an imbalance among several neurotransmitter and/or neuromodulator systems. Neurochemicals which have been studied included: catecholamines; acetylcholine; tryptophan and its metabolites; the amino acids gamma-aminobutyric acid (GABA), glutamate, phenylalanine and p tyrosine; trace amines; opioid peptides; cyclic AMP and androgenic hormones. A suitable animal model of TS would do much to advance our understanding of this disorder, and there are some interesting recent developments in this regard. PMID- 22297769 TI - alpha 2-Adrenoreceptor antagonism may contribute to the atypical properties of risperidone: experimental support for the Nutt case. AB - The therapeutic efficacy and reduction in side effects claimed for new antischizophrenic drugs such as clozapine and risperidone have been ascribed to their heightened affinity for serotonin 5-HT(2) receptors rather than D-2 receptors. A case for alpha(2)-adrenoreceptor antagonism has recently been argued. We have confirmed that at least one atypical property of risperidone (a rapid decrement in its ability to depress self-stimulation) can be partly prevented by an alpha(2)-adrenoreceptor agonist (clonidine) but not by a 5-HT( 2) receptor agonist (DOI). This result supports the suggested role of alpha( 2) adrenoreceptor antagonism in counteracting extrapyramidal effects during treatment with risperidone. PMID- 22297770 TI - Bupropion and sertraline combination treatment in refractory depression. AB - A sizeable minority of depressed patients, estimated at 15-20%, suffer chronic symptoms which often persist despite appropriate treatment. The search for new, more efficacious pharmacotherapies has included testing existing medications for additional therapeutic effects, such as in combination treatment. Four treatment- refractory patients who presented to the authors for clinical care are described, in which the combination of bupropion and sertraline was effective for a major depressive episode. None of the patients experienced adverse effects. Two carried the diagnosis of unipolar depression, and two, bipolar disorder. All had prior adequate, but ineffective, separate trials of buproprion and a selective serotonin re-uptake inhibitor (SSRI), including sertraline. All had chronic depression with multiple failed medication treatments, arguing against the alternative explanation that their improvement represented a placebo response or spontaneous remission. The efficacious combination of sertraline and bupropion may be due to synergism of its two distinct antidepressant mechanisms involving serotonergic, dopaminergic and noradrenergic systems. PMID- 22297771 TI - Origins of the BAP. PMID- 22297773 TI - A phenomenological approach to assessing a DUI/DWI program. AB - In an effort to find a more proactive solution to the problem of drunk driving, a midwestern city has implemented a Driving Under the Influence or Driving While Impaired (DUI/DWI) Court program, a derivative of the popular drug courts. Eligible participants are those who have had two or more drunk-driving offenses but who have not been convicted of a violent offense. Participants volunteer for a 36-week program in exchange for a suspension of their prison sentence. Program elements include drug/alcohol monitoring, support groups, counseling, and extensive supervision. Using a phenomenological approach, this article describes the challenges faced by 20 participants, how they navigated the program requirements, their key realizations about their conditions, and their views on the viability and effectiveness of the program. The article uses qualitative interviews of participants and stakeholders collected for a process evaluation of the DUI program, and official records collected for programming purposes. Findings from this research can be used broadly for programming purposes and can be used by other court jurisdictions that are developing similar programs. PMID- 22297774 TI - A reanalysis of the self-appraisal questionnaire: psychometric properties and predictive validity. AB - This research reassessed the psychometric properties and predictive validity of the Self-Appraisal Questionnaire (SAQ) in response to published criticism of the authors' earlier work. The current research used a much longer recidivism tracking-period, a different measure of recidivism, a larger sample, and more advanced analytic techniques than the original. Examination of the SAQ's psychometric properties continued to indicate that three of the six recidivism prediction subscales exhibited substandard levels of reliability and four of these subscales were not unidimensional. Yet, in contrast to the author's earlier results, the current analyses found that SAQ total score modestly predicted reconviction. PMID- 22297775 TI - Ergonomic analysis on work activity and training. PMID- 22297776 TI - Towards understanding and managing the learning process in mail sorting. AB - OBJECTIVE: This paper was based on case study research at the Swedish Mail Service Division and it addresses learning time to sort mail at new districts and means to support the learning process on an individual as well as organizational level. PARTICIPANTS: The study population consisted of 46 postmen and one team leader in the Swedish Mail Service Division. METHODS: Data were collected through measurements of time for mail sorting, interviews and a focus group. RESULTS: The study showed that learning to sort mail was a much more complex process and took more time than expected by management. Means to support the learning process included clarification of the relationship between sorting and the topology of the district, a good work environment, increased support from colleagues and management, and a thorough introduction for new postmen. CONCLUSIONS: The identified means to support the learning process require an integration of human, technological and organizational aspects. The study further showed that increased operations flexibility cannot be reinforced without a systems perspective and thorough knowledge about real work activities and that ergonomists can aid businesses to acquire this knowledge. PMID- 22297777 TI - Training, age and technological change: difficulties associated with age, the design of tools, and the organization of work. AB - OBJECTIVE: This article presents two ergonomic studies carried out when two French administrative bodies modernized their work tools. Our objective was to identify and define the vocational learning of experienced technicians who were required to adopt new working methods to cope with these technological changes. METHODS: We observed the work activity of technicians of different ages and length of service both before and during training, and also after their return to their work unit during the appropriation phase. RESULTS: These two studies revealed some difficulties that were common to all the technicians and others that were more specific to the older employees. In terms of the design of the training course, we were able to point out some mistaken assumptions about the technicians' original command of the work activity and the computers, which made it difficult for them to adopt new work procedures. CONCLUSION: The difficulties encountered by the older employees were ultimately found to be more an indication of organizational problems to do with the management of change rather than training problems due to age. PMID- 22297778 TI - Training yourself while training students: the constant challenge of vocational training teachers. AB - OBJECTIVE: This study characterized teachers' work at a vocational training (VT) center and the conditions under which the activity is learned. METHODS: We interviewed administrators and 12 teachers (4 males, 8 females) representing three study programs, selected as representative (age, seniority, and employment status). RESULTS: What emerged was a portrait of an evolving profession within an organization that was highly structured in terms of the assignment of tasks and schedules, but unstructured in terms of support for job adaptation and job retention. The major challenges for the teachers were to integrate their trade specific knowledge with the new skills required to teach the trade, and to find time for class preparation. The lack of resources and support caused dissatisfaction, stress, problematic work-study-family balance, and health problems, particularly among new teachers. DISCUSSION: A passion for teaching seems to compensate partly for these difficulties but it is uncertain for how long. Further research is necessary in order to understand the coping strategies employed by vocational training teachers. CONCLUSION: The findings of this study offer guidance for the development of resources that can assist with learning and performing the work of a VT teacher, and for a better recognition of the work of VT teachers. PMID- 22297779 TI - Entering the workforce and on-the-job skills acquisition in the construction sector. AB - OBJECTIVE: This paper presents a research project focused on the induction of newly hired employees in the construction sector in France, a sector in which employers report difficulties in retaining newly hired employees. The objective was to identify the diversity of new workers' employment status, and to understand what happens after they are hired, with a particular focus on the ways in which skills are acquired and passed on by the various protagonists. PARTICIPANTS: 25 employees, all men, voluntarily took part in this study. They were all employed, in various worksite jobs, under unlimited term contracts. METHODS: Interviews were recorded with each participant. They were analyzed using a thematic analysis method with the aim of reconstituting newcomers' career paths. RESULTS: Although the new employees have four different types of employment status, the way in which they learn the job is both relatively uniform and rudimentary. Skills are acquired in an opportunistic manner, often at the initiative of the newly hired employee, with older employees lacking the resources and the time to pass on their know-how. CONCLUSIONS: These findings raise issues related to workplace safety and organization--the dual focus of the debate on conditions conducive to skills transmission. PMID- 22297780 TI - Impacting working conditions through trade union training. AB - OBJECTIVE: This article presents a training course in work analysis via an understanding of real work. The course was aimed at trade unionists and was produced by researchers in ergonomics and occupational medicine. Designing this type of training is closely associated with the history of ergonomics in France and goes back to the basic principles: training by and for action, focusing on the concept of activity and the co-construction of knowledge, involving all actors in the relevant area of work. PARTICIPANTS: One hundred and fifty trade unionists were trained over a period of 18 months, successfully completing company projects in the field of occupational health. METHODS: The course was organised into seven 3-day modules. Each module included plenary sessions on fundamental topics relating to health/work, and small work groups where the trade union projects were prepared, based on gaining an understanding of the real work involved. RESULTS: There were two types of results: an understanding of the way work is currently changing and of the consequences of these changes for workers' health; transformations in trade unionists' representations of work, giving them a better awareness of health/work relationships, new ways of transforming work, and also information about the teaching content required when designing training programmes for trade unionists. CONCLUSION: Understanding the notion of activity and constructing interaction with employees are crucial elements for carrying out this type of project successfully. PMID- 22297781 TI - Suggested evaluation approach for health and safety training. AB - OBJECTIVE: The aim of this paper is to put forward a qualitative approach for evaluating the effects of training aiming to prevent health and safety problems at work. PARTICIPANT: One training performed by 2 trainers for 7 trainees. METHOD: a content analysis at different steps of the training course. RESULTS: The evaluation used, provides feedback about barriers and drivers in the training implementation context. Barriers are those factors, which undermine the implementation of action and the production of results while drivers, on the other hand, help to improve training and produce positive effects. CONCLUSIONS: The evaluation set up also provides useful information about the links between the training process and the results produced in work situations. PMID- 22297782 TI - An analysis of co-piloting in the teaching-learning process: a case study of science class debate. AB - In an ergonomic psychology approach, the teaching-learning process is considered a dynamic environment which emphasizes co-piloting by the teacher and the pupils. We suggest identifying exactly who takes charge in various co-piloting situations. This stems from observations of two videos of one teacher during two separate sessions of the same science class debate, carried out in different classes (the teacher's own class and an unknown class). The consideration of the teacher's and the pupils' positions towards a common reference point, comprised of posters presented by groups of pupils, as well as through pointing and indicating, allows for joint attention. This aims to identify traces of interactional modalities around a specific point of reference. This study has found that the teacher intervenes more often in a situation with an unknown class. PMID- 22297783 TI - Transmission of vocational skills between experienced and new hospital workers. AB - OBJECTIVES: This article presents the results of a study currently underway looking at the transmission of vocational skills between health care workers in a French hospital. The aim was to show that health care workers, in addition to their work with patients, also have to incorporate the transmission of vocational skills into their daily activities. METHODS: Thirteen transmission situations were observed and analyzed by means of an activity-focused ergonomic work analysis, with the aim of reporting on this "invisible work". PARTICIPANTS: The population studied was composed of nurses and the nursing assistants from three different units in one hospital. RESULTS: The results show that the work required to integrate and supervise new staff members is left to the discretion of health care workers. This means they are constantly required to arbitrate on both an individual and collective basis between providing health care for patients and supporting new members of staff. The content of the transmission goes beyond the prescribed tasks and technical knowledge, as staff members also pass on their professional strategies (individual and collective), rules of practice and ethical considerations. Supervising students also offers experienced workers the opportunity to share their professional practices. CONCLUSIONS: This study highlights the issues arising from this transmission activity for the experienced workers, new workers, patients and the hospital. PMID- 22297784 TI - What are the consequences of sharing a trainee's driving course between different trainers? AB - OBJECTIVES: In some driving schools in France, several trainers may successively train a single trainee. This situation can be described as a case of asynchronous collaboration. In this paper, we examine the consequences of this situation in two different studies: the first explores the trainers' activity while the second concerns the trainees. PARTICIPANTS: The participants in the first study were 6 trainers with different levels of experience, each working with 2 different trainees. Four of them met their trainees for the very first time. The second study included 150 trainees from 13 driving schools in Paris. METHODS: In the first study, the driving lessons were recorded and fully transcribed before a thematic analysis was conducted. In the second study, the trainees completed a questionnaire. We collected both socio-demographic and driver training data. RESULTS: In the first study, we observed that changing trainers during a trainee's driving course had an impact on the trainers' activity. We identified difficulties in establishing a diagnosis of the trainee's progress, and the organization of the driving lesson was altered. The second study highlighted the fact that changing trainers at the beginning of a course increased the duration of the training period. CONCLUSION: The impacts of changing trainers during a trainee's driving course are discussed with regard to both the trainers' scaffolding activity and the trainees' skill development. PMID- 22297785 TI - Temporalities in evaluation of training courses: standards and restrictions practiced by human resources professionals. AB - OBJECTIVE: This paper aims to decode the activity of Human Resources (HR) professionals responsible for evaluating continuing vocational training. It is based on the understanding of the different "time frames" involved in the development of the evaluation process as well as the reasons that justify the options for different implementation methods in the world of work. METHODS: Document analysis of the training evaluation process implemented in two companies and comparison of the results obtained in the evaluation of a specific training session using two different evaluation methods. RESULTS: In both cases the companies largely adopted the Kirkpatrick's model to evaluate training, although they hardly exceed the evaluation level reaction to training. One of the two companies offered the opportunity to carry out an evaluation procedure inspired in an alternative model that confirms that different evaluation methods lead to different analysis produced by the trainees regarding the process they have experienced. CONCLUSIONS: The choice for a specific training evaluation model usually depends on administration "time frames" and options and it usually entails a consensus that considers training evaluation as the fulfillment of previously determined standard procedures. Nevertheless, the use of alternative evaluation methods, as a complement to that already in use, may be the right way to revisit the questions which originated the training course and rethink not only its original design but also the working conditions associated to it. PMID- 22297786 TI - Narrative reflections on occupational transitions. PMID- 22297787 TI - Current world literature. PMID- 22297789 TI - High dose stereotactic body radiotherapy using three fractions for colorectal oligometastases. AB - BACKGROUND AND OBJECTIVES: This study evaluated the treatment result of high dose stereotactic body radiation therapy (SBRT) for colorectal oligometastases. METHODS: Between 2003 and 2009, 41 patients with 50 lesions confined to one organ from colorectal cancer (CRC) and treated with high dose SBRT >=45 Gy were retrospectively reviewed. Lymph nodes (LNs) (18 patients) were the most frequent sites followed in order by lung (12) and liver (11). SBRT doses ranged from 45 to 60 Gy in three fractions (median 48 Gy). The cumulative gross tumor volume (GTV) ranged from 2 to 123 ml (median 13 ml). RESULTS: The median follow-up period from the SBRT date was 28 months (range, 6-65 months). The 3-year local control and overall survival rates were 64 and 60%, and the respective 5-year rates were 57 and 38%. Cumulative GTV and SBRT dose were statistically significant prognostic factors for local control. The grade 3 or 4 complications occurred in three patients (7%). CONCLUSIONS: High dose SBRT for colorectal oligometastases was found to produce results comparable with surgical series. To improve local control, dose higher than 48 Gy are recommend when possible, but further study will be required to define the optimal normal tissue constraints and acceptable toxicity. PMID- 22297790 TI - Use of alcohols as reducing agents for synthesis of well-defined polymers by AGET ATRP. AB - Alcohols have been demonstrated to be efficient reducing agents for AGET-ATRP for the first time. Well-controlled polymerizations have been successfully achieved with the typical characteristics of "living"/controlled radical polymerization. PMID- 22297791 TI - Effects of visible and UV light on the characteristics and properties of crude oil-in-water (O/W) emulsions. AB - The effects of visible and UV light on the characteristics and properties of Prudhoe Bay (PB) and South Louisiana (SL) emulsions were investigated to better understand the role of sunlight on the fate of spilled crude oils that form emulsions with a dispersant in the aquatic environment. Before irradiation, crude oil emulsions showed the presence of dispersed crude oil micelles in a continuous water phase and crude oil components floating on the surface. The crude oil micelles decreased in size with irradiation, but emulsions retained their high degree of polydispersity. UV irradiation reduced the stability of emulsions more effectively than visible light. The reduction of micelles size caused the viscosity of emulsions to increase and melting point to decrease. Further, irradiation increased acid concentrations and induced ion formation which lowered the pH and increased the conductivity of emulsions, respectively. Ni and Fe in PB emulsions were extracted from crude oil with UV irradiation, which may provide an efficient process for metal removal. The emulsions were stable toward freeze/thaw cycles and their melting temperatures generally decreased with irradiation. Evidence of OH production existed when emulsions were exposed to UV but not to visible light. The presence of H(2)O(2) enhanced the photodegradation of crude oil. Overall, the changes in emulsion properties were attributed to direct photodegradation and photooxidation of crude oil components. PMID- 22297792 TI - Analyzing atopic and non-atopic asthma. AB - There is a need to better define phenotypes of asthma. However, many studies have data available only on asthma and atopy, so they are often used to define 'atopic' and 'non-atopic' asthma. We discuss and illustrate the problems of analyzing such outcomes. We used the 31 year follow-up of the Northern Finland Birth Cohort 1966 (n=5,429). 'Atopic asthma' and 'non-atopic asthma' were defined based on presence or absence of atopy (any skin prick test >=3 mm) at age 31. Gender and ownership of cat in childhood were used as risk factors. Simple calculations on hypothetical datasets were used to support the conclusions. 'Atopic asthma' and 'non-atopic asthma', are not well separated disease entities. The association of a risk factor with 'atopic asthma' and 'non-atopic asthma' is determined both by its association with asthma and with atopy. E.g. if a risk factor is not associated with asthma, but is protective for atopy, this will produce a protective association with 'atopic asthma', but an opposite association with 'non-atopic asthma'. This is the result from the typical analysis, which uses all non-asthmatics as the comparison group. Valid results, unconfounded by atopy, can be gained by comparing asthmatics to nonasthmatics separately among atopics and non-atopics, i.e. by doing the analysis stratified by atopy. If data only on asthma and atopy are available, asthma and atopy should be analyzed at first as separate outcomes. If atopic and nonatopic asthma are used as additional outcomes, valid results can be gained by stratifying the analysis by atopy. PMID- 22297793 TI - Short- and long-term changes in gastric morphology and histopathology following sleeve gastrectomy in diet-induced obese rats. AB - BACKGROUND: Sleeve gastrectomy (SG) has been used as a multipurpose surgical procedure for the treatment of morbid obesity. The aim of the study was to analyze gastric morphology and histology at two different time points after SG in rats. METHODS: Thirty-five male Wistar rats were fed ad libitum during 3 months on a high-fat diet to induce obesity. Subsequently, 25 diet-induced obese rats underwent either SG (n = 12) or a sham operation (n = 13). The remaining ten obese animals encompassed the nonoperated control group (Co). Four weeks postoperatively, 15 rats (n = 5 rats/experimental group) were sacrificed, while the remaining 20 rats were sacrificed after 16 weeks (animals/group; Co = 5, sham = 8, SG = 7) to compare the gastric morphological and histopathological changes over time. Body weight and food intake were regularly recorded. RESULTS: For both time periods, the Co groups exhibited the highest body weight, while the rats undergoing the SG showed the lowest weight gain (P < 0.05). Initially, significant differences (P < 0.005) in food intake relative to body weight were observed between the Co rats and animals undergoing surgery, which disappeared thereafter. The actual total stomach size after both experimental periods in the SG group was similar to that of non- and sham-operated rats mainly due to a forestomach enlargement, which was more pronounced after 16 weeks. Traits of gastritis cystica profunda characterized by gastric foveolae elongation with hyperplasia and cystic dilatation of the glands were observed in the residual stomachs of the sleeve-gastrectomized rats. These findings were mostly observed after 16 weeks of performing the SG, although they were also detected occasionally following 4 weeks postoperatively. No intestinal metaplasia was observed. CONCLUSION: After SG gastric macro- and microscopic changes with functional implications in both the short and long term take place. PMID- 22297794 TI - Dual renin-angiotensin system blockade. PMID- 22297795 TI - English NHS hospital activity: doing less (with less or the same)? PMID- 22297796 TI - Into the abyss? How the health bill affects the NHS. PMID- 22297797 TI - FDA is sued for allegedly violating privacy of employees. PMID- 22297798 TI - Former head of legal services at Mid Staffordshire wins 103,000 pound award from trust. PMID- 22297799 TI - Intracellular refolding assay. AB - This protocol describes a method to measure the enzymatic activity of molecular chaperones in a cell-based system and the possible effects of compounds with inhibitory/stimulating activity. Molecular chaperones are proteins involved in regulation of protein folding and have a crucial role in promoting cell survival upon stress insults like heat shock, nutrient starvation and exposure to chemicals/poisons. For this reason chaperones are found to be involved in events like tumor development, chemioresistance of cancer cells as well as neurodegeneration. Design of small molecules able to inhibit or stimulate the activity of these enzymes is therefore one of the most studied strategies for cancer therapy and neurodegenerative disorders. The assay here described offers the possibility to measure the refolding activity of a particular molecular chaperone and to study the effect of compounds on its activity. In this method the gene of the molecular chaperone investigated is transfected together with an expression vector encoding for the firefly luciferase gene. It has been already described that denaturated firefly luciferase can be refolded by molecular chaperones. As normalizing transfection control, a vector encoding for the renilla luciferase gene is transfected. All transfections described in this protocol are performed with X-treme Gene (Roche) in HEK-293 cells. In the first step, protein synthesis is inhibited by treating the cells with cycloheximide. Thereafter protein unfolding is induced by heat shock at 45 degrees C for 30 minutes. Upon recovery at 37 degrees C, proteins are re-folded into their active conformation and the activity of the firefly luciferase is used as read-out: the more light will be produced, the more protein will have re-gained the original conformation. Non-heat shocked cells are set as reference (100% of refolded luciferase). PMID- 22297800 TI - cGMP becomes a drug target. AB - Cyclic guanosine 3',5'-monophosphate (cGMP) serves as a second messenger molecule, which regulates pleiotropic cellular functions in health and disease. cGMP is generated by particulate or soluble guanylyl cyclases upon stimulation with natriuretic peptides or nitric oxide, respectively. Furthermore, the cGMP concentration is modulated by cGMP-degrading phosphodiesterases. Several targets of cGMP are utilized to effect its various cellular functions. These effector molecules comprise cGMP-dependent protein kinases, ion channels, and phosphodiesterases. During the last decade, it emerged that cGMP is a novel drug target for the treatment of pulmonary and cardiovascular disorders. In this respect, several drugs were developed, which are now in clinical phase studies for, e.g., pulmonary hypertension or cardiovascular diseases. These new drugs act NO-independently with/without heme on soluble guanylyl cyclases or induce subtypes of particular guanylyl cyclases and thereby lead to new therapeutic concepts and horizons. In this regard, the fifth cGMP meeting held in June 2011 in Halle, Germany, comprised the new therapeutic challenges with the novel functional and structural concepts of cGMP generating and effector molecules. This report summarizes the new data on molecular mechanisms, (patho)physiological relevance, and therapeutic potentials of the cGMP signaling system that were presented at this meeting. PMID- 22297801 TI - Biliary stenting: indications, choice of stents and results: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline. AB - This article is part of a combined publication that expresses the current view of the European Society of Gastrointestinal Endoscopy about endoscopic biliary stenting. The present Clinical Guideline describes short-term and long-term results of biliary stenting depending on indications and stent models; it makes recommendations on when, how, and with which stent to perform biliary drainage in most common clinical settings, including in patients with a potentially resectable malignant biliary obstruction and in those who require palliative drainage of common bile duct or hilar strictures. Treatment of benign conditions (strictures related to chronic pancreatitis, liver transplantation, or cholecystectomy, and leaks and failed biliary stone extraction) and management of complications (including stent revision) are also discussed. A two-page executive summary of evidence statements and recommendations is provided. A separate Technology Review describes the models of biliary stents available and the stenting techniques, including advanced techniques such as insertion of multiple plastic stents, drainage of hilar strictures, retrieval of migrated stents and combined stenting in malignant biliary and duodenal obstructions.The target readership for the Clinical Guideline mostly includes digestive endoscopists, gastroenterologists, oncologists, radiologists, internists, and surgeons while the Technology Review should be most useful to endoscopists who perform biliary drainage. PMID- 22297802 TI - Creatine phosphate: pharmacological and clinical perspectives. AB - Since the 1970s, extensive experimental and clinical research has demonstrated that relevant reductions of creatine phosphate (CrP) or phosphocreatine availability occur in a wide spectrum of pathophysiological situations. A decrease in intracellular concentrations of creatine (Cr) and CrP results in a hypodynamic state of cardiac and skeletal muscle pathology. Many experimental and clinical studies have evaluated the possibility to improve cardiac and skeletal muscle performance by exogenous administration of CrP. Furthermore, many experimental studies have shown that CrP may play two important roles in the regulation of muscle energetics and work. First, CrP maintains local adenosine triphosphate pools and stabilizes cellular membranes due to electrostatic interactions with phospholipids. The second mechanism decreases the production of lysophosphoglycerides in hypoxic hearts, protects the sarcolemma of cardiac cells against ischemic damage, decreases the frequency of arrhythmias, and increases post-ischemic recovery of contractile function. Recent research on CrP has demonstrated positive therapeutic results in various clinical applications. These benefits have been applied in several pathological conditions, such as heart failure, acute myocardial ischemia, chronic ischemic heart disease, cardiac surgery, skeletal muscle hypotonotrophy, and cerebral ischemia. This review describes the CrP shuttle, pathophysiological basis of the supplementation of CrP, and its therapeutic effects in multiple clinical conditions. The major aim is to summarize results of the intense research carried out over 40 years to provide evidence to support the adjunctive use of CrP in many pathological conditions that may target cellular energy impairment; thus, increasing energy metabolism. PMID- 22297803 TI - Anti-inflammatory effects of aerobic exercise in mice exposed to air pollution. AB - PURPOSE: Exposure to diesel exhaust particles (DEP) results in lung inflammation. Regular aerobic exercise improves the inflammatory status in different pulmonary diseases. However, the effects of long-term aerobic exercise on the pulmonary response to DEP have not been investigated. The present study evaluated the effect of aerobic conditioning on the pulmonary inflammatory and oxidative responses of mice exposed to DEP. METHODS: BALB/c mice were subjected to aerobic exercise five times per week for 5 wk, concomitantly with exposure to DEP (3 mg.mL(-1); 10 MUL per mouse). The levels of exhaled nitric oxide, reactive oxygen species, cellularity, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF alpha) were analyzed in bronchoalveolar lavage fluid, and the density of neutrophils and the volume proportion of collagen fibers were measured in the lung parenchyma. The cellular density of leukocytes expressing IL-1beta, keratinocyte chemoattractant (KC), and TNF-alpha in lung parenchyma was evaluated with immunohistochemistry. The levels of IL-1beta, KC, and TNF-alpha were also evaluated in the serum. RESULTS: Aerobic exercise inhibited the DEP-induced increase in the levels of reactive oxygen species (P < 0.05); exhaled nitric oxide (P < 0.01); total (P < 0.01) and differential cells (P < 0.01); IL-6 and TNF-alpha levels in bronchoalveolar lavage fluid (P < 0.05); the level of neutrophils (P < 0.001); collagen density in the lung parenchyma (P < 0.05); the levels of IL-6, KC, and TNF-alpha in plasma (P < 0.05); and the expression of IL 1beta, KC, and TNF-alpha by leukocytes in the lung parenchyma (P < 0.01). CONCLUSIONS: We conclude that long-term aerobic exercise presents protective effects in a mouse model of DEP-induced lung inflammation. Our results indicate a need for human studies that evaluate the pulmonary responses to aerobic exercise chronically performed in polluted areas. PMID- 22297804 TI - Correlates of change in adults' television viewing time: a four-year follow-up study. AB - PURPOSE: Adults tend to increase their television (TV) viewing time as they age, but little is known about attributes associated with change in TV viewing over time. This study examined individual, social, and environmental correlates of change in TV viewing time for 4 yr. METHODS: Adult participants (n = 897) from a longitudinal epidemiological study in Adelaide, Australia, reported TV viewing time at baseline (2003-2004) and at follow- up (2007-2008). Generalized linear modeling was used to examine correlates of change in TV viewing time. RESULTS: The mean TV viewing time increased from 112 to 116 min.d(-1) from baseline to follow-up. Adjusted for TV viewing time at baseline, having a tertiary education was associated with a 13% lower TV time at follow-up (P = 0.007). Each additional hour of occupational and transport physical activity at baseline was associated with a 2% and 7% lower TV viewing at follow-up (P = 0.031 and P = 0.023, respectively). For men, an additional hour of domestic physical activity was associated with a 7% higher TV viewing time at follow-up (P = 0.006). A significant neighborhood walkability * working status interaction (P = 0.035) indicated that, for those who were not working, living in a highly walkable neighborhood was associated with a 23% lower TV viewing time at follow-up (P = 0.003). CONCLUSIONS: Adults with lower educational attainment, adults with lower occupational and transport physical activity, men with higher domestic physical activity, and nonworking adults living in lowly walkable neighborhoods were at higher risk of increase in TV viewing time. Interventions should target multiple variables at the individual, social, and environmental levels to address age related increases in TV viewing time. PMID- 22297805 TI - Influence of exercise on airway epithelia in cystic fibrosis: a review. AB - Regular exercise is recommended as part of cystic fibrosis (CF) physiotherapy. Exercise delays the development of pulmonary disease in CF patients; however, the cellular mechanisms responsible for these improvements are unclear. This review expands on the hypothesis that exercise improves CF pathophysiological ion dysregulation via purinergic and adrenergic pathways by describing the effects of 5' adenosine monophosphate-activated protein kinase (AMPK), atrial natriuretic peptide (ANP), and arginine-vasopressin (AVP) on CF airway epithelia. Activation of AMPK decreases Na(+) absorption, increases airway surface liquid, and reduces oxidative stress and inflammation. Plasma ANP inhibits the basolateral Na(+)/K(+) ATPase and may therefore reduce epithelial water absorption. Airway epithelia respond to plasma AVP and secrete AVP in response to elevated bradykinin. AVP stimulates the basolateral Na(+)/K(+)/2Cl(-) exchanger, thereby increasing Cl(-) secretion, reducing Na(+) absorption, and promoting basolateral to luminal water flux. In addition, AVP may increase cilia beat frequency in airway epithelia via a Ca(2+)-dependent mechanism. This review will describe the effects of exercise on AMPK activation, ANP release, and AVP secretion; we hypothesize that the mechanical and metabolic perturbations that occur with exercise may be beneficial in preventing CF lung pathogenesis by improving airway hydration, mucociliary clearance, and reducing markers of inflammation. PMID- 22297806 TI - Effects of a three-year intervention: the Copenhagen School Child Intervention Study. AB - INTRODUCTION: This study assessed short-term and long-term effects of a 3-yr controlled school-based physical activity (PA) intervention on fatness, cardiorespiratory fitness (VO(2peak)) and CVD risk factors in children. METHODS: The study involved 18 schools (10 intervention and 8 controls) and included a follow-up 4 yr after the end of intervention. The analyses included 696, 6- to 7 yr-old children at baseline, 612 postintervention (age 9.5 yr) and 441 at follow up (age 13.4 yr). The intervention consisted of a doubling of the amount of physical education (PE; from 90 to 180 min.wk(-1)), training of PE teachers, and upgrading of PE and playing facilities. Anthropometrics and systolic blood pressure (SBP) were measured. VO(2peak) was directly measured, and PA was assessed using accelerometry. Fasting blood samples were analyzed for CVD risk factors. A composite risk score was computed from z-scores of SBP, triglycerides, total cholesterol-to-HDL cholesterol ratio, homeostatic model assessment (HOMA score), skinfolds, and inverse VO(2peak). RESULTS: The HOMA score of the intervention group boys had a smaller increase from baseline to postintervention compared with control boys (P = 0.004). From baseline to follow-up intervention group boys had a smaller increase in SBP compared with control boys (P = 0.010). There were no other significant differences between groups. CONCLUSIONS: This 3 yr school-based PA intervention caused positive changes in SBP and HOMA score in boys but not in girls, and no effects were seen in PA, VO(2peak), fatness, and the other measured CVD risk factors. Our results indicate that a doubling of PE and providing training and equipment may not be sufficient to induce major improvements in CVD risk factors in a normal population. PMID- 22297807 TI - Developing a self-reported physical fitness survey. AB - Physical fitness measures indicate health status, and these can be used to improve management of overall health. PURPOSE: This study aimed to describe the development of a self-reported fitness (SRFit) survey intended to estimate fitness in adults age >=40 yr across four domains: 1) muscular strength and endurance, 2) cardiovascular fitness, 3) flexibility, and 4) body composition. METHODS: SRFit items were developed from the previously validated Rikli and Jones Senior Fitness Test battery of physical tests. Face-to-face participant interviews were used to refine SRFit item wording. Data from a pilot administration of the SRFit survey were used to guide further revisions of SRFit items. The Senior Fitness Test battery was used to evaluate the four fitness domains. The BodPod was used to measure body composition. Height, weight, and resting blood pressure were measured, and the revised SRFit survey was administered to 108 participants. RESULTS: Forty-five percent of the participants were women and 37% reported being black or in the "other" race category. Mean age was 53.5 +/- 8.0 yr and mean body mass index was 30.6 +/- 8.8 kg.m(-2). Mean +/- SD SRFit summary scores and correlations found between summary and fitness test scores were as follows: upper body strength = 12.8 +/- 2.4, r = 0.59, P < 0.001; lower body strength = 12.6 +/- 2.6, r = 0.68, P < 0.001; upper body flexibility (left side) = 12.3 +/- 2.8, r = 0.47, P < 0.001; upper body flexibility (right side) = 12.4 +/- 2.8, r = 0.67, P < 0.001; lower body flexibility = 17.4 +/- 3.8, r = 0.55, P < 0.001; cardiovascular endurance = 12.9 +/- 2.6, r = 0.66, P < 0.001; body mass index = 7.7 +/- 2.23, r = 0.79, P < 0.001; and percent body fat = 7.7 +/- 2.2, r = 0.78, P < 0.001. CONCLUSIONS: SRFit survey items in each fitness domain were correlated with analogous Senior Fitness Test items, indicating that participants can accurately use the SRFit survey to self-report physical fitness. PMID- 22297808 TI - Neuromuscular function during a forward lunge in meniscectomized patients. AB - OBJECTIVE: This study aimed to investigate differences in knee joint kinematics, ground reaction force kinetics and neuromuscular activity including muscle coactivation, and medial versus lateral muscle activity during a forward lunge between the operated and contralateral legs of meniscectomized patients. Such differences may represent early changes in neuromuscular function potentially contributing to the development of knee osteoarthritis. METHODS: Twenty-two unilaterally meniscectomized patients (15 men and 7 women; age = 45.4 +/- 5.1 yr, height = 174.3 +/- 7.1 cm, weight = 77.3 +/- 15.4 kg (mean +/- SD)) were investigated on their operated and contralateral legs during a forward lunge using synchronous goniometer, force plate, and EMG recording (vastus lateralis, vastus medialis, biceps femoris, and semitendinosus). RESULTS: During impact loading, an increased level of muscle coactivation (38.0% (29.8%-46.3%) vs 30.1% (23.6%-36.6%), P = 0.02; mean (95% confidence interval)), reduced range of motion (59.4 degrees (54.5 degrees -64.2 degrees ) vs 64.9 (60.8 degrees -70.0 degrees ), P = 0.01), and increased loading rate (985% BW.s(-1) (653-1317% BW.s(-1)) vs 696% BW.s(-1) (525-868% BW.s(-1)), P = 0.01) were observed in the operated leg compared with the contralateral leg. In addition, different patterns of medial versus lateral neuromuscular activity were observed in the operated and contralateral legs, along with minor differences during the other phases of the forward lunge. CONCLUSIONS: The findings of increased muscle coactivation, reduced range of motion, and increased loading rate in the operated compared with the contralateral leg support the hypothesis that meniscectomized patients demonstrate modulations in kinetics, kinematics, and neuromuscular activity, which may represent early changes in neuromuscular function that precede and affect development of knee osteoarthritis. The results also indicate that the forward lunge test is a sensitive measure to identify leg-to-leg differences in neuromuscular function after surgical interventions. PMID- 22297809 TI - Airway dysfunction and inflammation in pool- and non-pool-based elite athletes. AB - PURPOSE: This study sought to determine and compare the levels of airway dysfunction and inflammation in a large cohort of symptomatic international athletes from pool- and non-pool-based sporting backgrounds. In total, 118 athletes were recruited. METHODS: All subjects had symptoms of exercise asthma and were steroid naive. They completed baseline spirometry, a symptom score, exhaled nitric oxide, a eucapnic voluntary hyperventilation (EVH) test, and a postchallenge induced sputum and urine test. RESULTS: Pool-based athletes had better lung function (FEV1 = 110% vs 102% predicted, mean difference = 8.200 +/- 2.339, P = 0.0006 and FVC = 5.64 vs 4.75 L, mean difference = 0.8855 +/- 0.1951, P < 0.0001) and more marked airways hyper-reactivity (AHR) (percent drop in FEV1 after EVH = 18.14 vs 11.47, mean difference = 6.67, 95% confidence interval = 2.89-10.53, P = 0.0009). More pool-based athletes had a positive EVH test (72% pool vs 39% nonpool), but there was no difference between groups with respect to eosinophilic inflammation (sputum eosinophil percentage: pool = 2.07, nonpool = 2.28, P = 0.77; exhaled nitric oxide: pool = 32.54, nonpool = 35.77, P = 0.60). Athletes with a positive EVH test had less neutrophilic inflammation (P = 0.01) and more epithelial cells (P = 0.03) in their sputum. CONCLUSIONS: Pool-based endurance athletes have greater evidence of AHR than non-pool-based athletes but no evidence of greater eosinophilic airway inflammation. Athletes who test positive on EVH are more likely to be eosinophilic and have higher levels of epithelial cells in their sputum. PMID- 22297810 TI - Increased expression of miR-34a in mouse spleen one day after exposure to N-ethyl N-nitrosourea. AB - MicroRNAs (miRNAs) are a class of single-stranded small RNA molecules (~22 nucleotides) that are not translated into proteins and function as regulators of gene expression. Many miRNAs are involved in carcinogenesis. One of them, miR 34a, is associated with various p53-initiated biological processes and may act as a tumor suppressor miRNA. Its expression is generally down-regulated in tumor tissues and up-regulated in tissues exposed to carcinogens chronically or subchronically. However, the response of this miRNA to acute exposure of a genotoxic carcinogen is little known. In this study, miR-34a expression was evaluated in spleen tissues of mice treated with a dose of 120 mg kg(-1) body weight N-ethyl-N-nitrosourea (ENU), a potent mutagenic carcinogen. Real-time PCR analysis showed that the ENU exposure resulted in a 5.5-fold increase of miR-34a expression over the control one day after the treatment. The result suggests that miR-34a expression responds sensitively to genotoxic insults within a short period after exposure of the mutagen, and therefore, this gene has the potential to be used as an indicator for genotoxin exposure. PMID- 22297811 TI - Arterial stiffness is not increased in teens with early uncomplicated type 1 diabetes mellitus. AB - People with type 1 diabetes mellitus are at an increased risk of cardiovascular mortality. Studies comparing arterial stiffness between subjects with type 1 diabetes and nondiabetic controls have provided controversial findings.We investigated brachial-ankle pulse wave velocity (baPWV) in 87 teenagers with type 1 diabetes mellitus and in 21 matched healthy controls. Our data show that baPWV was not increased in teenagers after a median illness of 5 years. PMID- 22297812 TI - Follow-up after primary treatment of soft tissue sarcoma of extremities: impact of frequency of follow-up imaging on disease-specific survival. AB - BACKGROUND AND OBJECTIVES: We explored the impact of frequency of surveillance imaging on disease-specific survival (DSS) in patients with extremity soft tissue sarcoma (STS). METHODS: Locoregional imaging (LRI) and chest imaging (CI) were used to detect local recurrence (LR) and distant metastasis (DM), respectively. Relapsing patients were retrospectively assigned to more frequent surveillance (MFS) or less frequent surveillance (LFS) groups, according to the median interval for each follow-up modality. Outcome measures included overall DSS (O DSS), post-LR DSS, and post-DM DSS. RESULTS: We assigned 165 patients to three distinct risk groups according to tumor size (<=5 vs. >5 cm), depth (superficial- vs. deep-seated), grade (I vs. II or III), and surgical margin (>=10 vs. <10 mm). Data for 80 patients who relapsed were analyzed. Among 50 high-risk (with all four risk factors) relapsing patients, those in the MFS group for either LRI or CI had better O-DSS (LRI, median 44.07 vs. 27.43 months, P = 0.008; CI, median 43.60 vs. 36.93 months, P = 0.036), post-LR DSS (median 27.20 vs. 10.63 months, P = 0.028) and post-DM DSS (median 13.20 vs. 6.24 months, P = 0.031). CONCLUSION: More frequent follow-up were associated with improved survival in high-risk relapsing patients with extremity STS by providing greater opportunities for adequate reoperation. PMID- 22297814 TI - Metal array fabrication through self-assembly of Pt-complex-bound amino acids. AB - A new type of Pt-complex-bound amino acid was synthesized by condensation of a cyclometalated Pt complex with the side-chain residue of N- and C-alkylated glutamic acid. Self-assembly of the Pt-bound lipophilic amino acid afforded a supramolecular gel in organic solvents, which comprised fibrous lamellar aggregates that supported a highly oriented Pt array. PMID- 22297816 TI - Personalized medicine: words that mean just what you choose? PMID- 22297815 TI - Chylomicron formation and secretion is required for lipid-stimulated release of incretins GLP-1 and GIP. AB - Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretins produced in the intestine that play a central role in glucose metabolism and insulin secretion. Circulating concentrations of GLP-1 and GIP are low and can be difficult to assay in rodents. These studies utilized the novel intestinal lymph fistula model we have established to investigate the mechanism of lipid-stimulated incretin secretion. Peak concentrations of GLP-1 and GIP following an enteral lipid stimulus (Liposyn) were significantly higher in intestinal lymph than portal venous plasma. To determine whether lipid-stimulated incretin secretion was related to chylomicron formation Pluronic L-81 (L-81), a surfactant inhibiting chylomicron synthesis, was given concurrently with Liposyn. The presence of L-81 almost completely abolished the increase in lymph triglyceride seen with Liposyn alone (P < 0.001). Inhibition of chylomicron formation with L-81 reduced GLP-1 secretion into lymph compared to Liposyn stimulation alone (P = 0.034). The effect of L-81 relative to Liposyn alone had an even greater effect on GIP secretion, which was completely abolished (P = 0.004). These findings of a dramatic effect of L-81 on lymph levels of GLP-1 and GIP support a strong link between intestinal lipid absorption and incretin secretion. The relative difference in the effect of L-81 on the two incretins provides further support that nutrient-stimulation of GIP and GLP-1 is via distinct mechanisms. PMID- 22297819 TI - Replication-competent retroviruses in gene-modified T cells used in clinical trials: is it time to revise the testing requirements? PMID- 22297820 TI - Signs of progress in gene therapy for muscular dystrophy also warrant caution. PMID- 22297821 TI - Cell-penetrating RNAs: new keys to the castle. PMID- 22297824 TI - Molecular weight effects on the miscibility behavior of dextran and maltodextrin with poly(vinylpyrrolidone). AB - PURPOSE: To characterize and interpret the miscibility of dextran and maltodextrin with poly(vinylpyrrolidone) (DEX-PVP) as a function of polymer molecular weights. METHODS: Blend miscibility was studied using 4 different molecular weight (MW) grades of DEX combined with 5 MW grades of PVP, over a broad compositional range. Miscibility was evaluated by inspection of glass transition events measured by differential scanning calorimetry (DSC). Fourier transform mid-infrared spectroscopy (FTIR), combined with curve fitting, was performed to characterize the extent of hydrogen bonding. The observed miscibility behavior was further interpreted in terms of mixing thermodynamics. RESULTS: Miscibility of the blends ranged from fully miscible to completely immiscible with multiple partially miscible systems observed. Increasing polymer molecular weight decreased miscibility. For the lowest DEX grade, hydrogen bonding was independent of PVP MW, as expected since all systems were completely miscible. Higher molecular weights of DEX resulted in reduced intermolecular hydrogen bonding and decreased miscibility, increasingly so for higher MW PVP grades. Evaluation of the mixing thermodynamics supported these findings. CONCLUSIONS: With higher combined molecular weights of DEX-PVP blends, phase behavior evolves from completely miscible to virtually immiscible. Concurrently, DEX-PVP hydrogen bonding decreases. From a thermodynamic perspective, the combinatorial mixing entropy was observed to decrease as the molecular weight of the polymers increased, providing a reduced counterbalance to the unfavorable mixing enthalpy thought to accompany this polymer combination. PMID- 22297825 TI - [Procedures according to data protection laws for coupling primary and secondary data in a cohort study: the lidA study]. AB - In the German health service research there exists, unlike in labour market research, no experience with the combination of personal primary and secondary data. One of the reasons for this is, among other things, data protection. The lidA cohort study analyses persons in employment (excluding civil servants and self-employed), born in 1959 and 1965. It is intended to give answers to questions from the health services research as well as from the labour market research. It relies on different primary and secondary data sources: survey data, process data from the Federal Employment Agency, aggregated and individual health insurance data. The experiences made in the lidA study, in addition to the data protection needs and the expenditures for the implementation, are summarised as "best practice". The procedure for the application process according to S 75 SGB X, the directive to develop data security concepts, the informed consent for the linkage of personal information are described and the importance of a transparent approach is explained. So far it has been shown that the preparation and approval process for the release of the actual data, both within the project consortium, but also with external parties such as health insurance companies or the responsible data protection officer, requires a major effort. In view of all the identified legal and organisational challenges, our findings should be extremely useful for answering different research questions in the fields of labour market and health services research. In combination with primary data, they may even represent a "gold standard" for epidemiology and health services research. PMID- 22297826 TI - [Health promotion within health care - analysis of employees' smoking habits, consequences for patient care and resources for future smoking cessation initiatives]. AB - Smoking is still one of the most dangerous and avoidable health risks. This study "Healthy air at work" analysed smoking habits, state of change, the influence of the diagnosis F.17.0 in patient treatment and estimation of subjective workloads and personal resources in health-care workers. Almost 2 000 questionnaires were analysed. 19.9% of this study population were smokers, while 26.4% were considered to be heavy or very heavy smokers. Half of the current smokers were willing to change, while the majority had already tried to quit multiple times. The most important motive to stop smoking was fear of consequences (44.4%), followed by other reasons (42.3%) (e. g., pregnancy) and expenses (33.9%). Protection against second-hand smoke was estimated mostly as very relevant, especially for patients. Being a role model in terms of tobacco consumption seems to be important for health-care workers. 61.3% of all health-care workers stated that patients' nicotine dependency had been diagnosed and out of these 46.5% say it is a relevant factor in therapy. 60% of all interviewed employees evaluated themselves as working quantitatively under heavy and very heavy workloads, while 20% had to deal with high qualitative challenges. In terms of future work ability and personal resources 75% were considerably optimistic. We did not find any relation in terms of workloads and smoking habits. Rather few health-care workers used nicotine replacement therapy during former cessation trials. Health-care workers could play an important role in the treatment and prevention of smoking dependency. This potential is not used to its full extent up to now. PMID- 22297827 TI - [Structures and practice of psychology departments in orthopaedic and cardiac rehabilitation: a comparison of outpatient and inpatient clinics in Germany]. AB - We aimed at comparing the present structural quality and practice of psychological services in ambulatory (outpatient) and inpatient rehabilitation in Germany.A nationwide survey of psychological services in orthopaedic and cardiac outpatient rehab centres was carried out. Results were compared to those of an identical study of inpatient services that was conducted simultaneously.Data were obtained from 81 ambulatory centres (return rate: 44%). Structures and practice (e. g., diagnostic procedures, psychological interventions) in ambulatory and inpatient rehabilitation only differed marginally. Differences concern the staff/patient ratio which is slightly better in ambulatory centres and some aspects of working conditions (e. g., less assisting staff or supervision).From its beginning, ambulatory rehabilitation in Germany has followed the standards of the inpatient model as far as structural quality and processes are concerned. Psychological practice in the ambulatory setting reflects that too. It is discussed whether the uniformity of ambulatory and inpatient rehabilitation services really is appropriate, or whether a more flexible model (e. g., regarding treatment duration) is needed in the German rehabilitation system. PMID- 22297828 TI - [Stress after labour - significance for maternal health behaviour]. AB - Maternal stress and lack of social support in the postpartum period have a negative impact on health behaviour of new mothers. Midwives can enhance mother's coping with stress and improve their social support by early interventions in postpartum care. PMID- 22297829 TI - The use of thermal infra-red imaging to detect delayed onset muscle soreness. AB - Delayed onset muscle soreness (DOMS), also known as exercise induced muscle damage (EIMD), is commonly experienced in individuals who have been physically inactive for prolonged periods of time, and begin with an unexpected bout of exercise, but can also occur in athletes who exercise beyond their normal limits of training. The symptoms associated with this painful phenomenon can range from slight muscle tenderness, to severe debilitating pain. The intensity of these symptoms and the related discomfort increases within the first 24 hours following the termination of the exercise, and peaks between 24 to 72 hours post exercise. For this reason, DOMS is one of the most common recurrent forms of sports injury that can affect an individual's performance, and become intimidating for many. For the last 3 decades, the DOMS phenomenon has gained a considerable amount of interest amongst researchers and specialists in exercise physiology, sports, and rehabilitation fields. There has been a variety of published studies investigating this painful occurrence in regards to its underlying mechanisms, treatment interventions, and preventive strategies. However, it is evident from the literature that DOMS is not an easy pathology to quantify, as there is a wide amount of variability between the measurement tools and methods used to quantify this condition. It is obvious that no agreement has been made on one best evaluation measure for DOMS, which makes it difficult to verify whether a specific intervention really helps in decreasing the symptoms associated with this type of soreness or not. Thus, DOMS can be seen as somewhat ambiguous, because many studies depend on measuring soreness using a visual analog scale (VAS), which is a subjective rather than an objective measure. Even though needle biopsies of the muscle, and blood levels of myofibre proteins might be considered a gold standard to some, large variations in some of these blood proteins have been documented, in addition to the high risks sometimes associated with invasive techniques. Therefore, in the current investigation, we tested a thermal infra red (IR) imaging technique of the skin above the exercised muscle to detect the associated muscle soreness. Infra-red thermography has been used, and found to be successful in detecting different types of diseases and infections since the 1950's. But surprisingly, near to nothing has been done on DOMS and changes in skin temperature. The main purpose of this investigation was to examine changes in DOMS using this safe and non-invasive technique. PMID- 22297830 TI - Alterations of color vision and central visual field in patients with Vogt Koyanagi-Harada syndrome. AB - PURPOSE: To investigate the changes of color vision and central visual field in a cohort of patients with Vogt-Koyanagi-Harada (VKH) syndrome. METHODS: Sixteen VKH patients (32 eyes) were enrolled in this study. All the patients were treated with immunosuppressive agents. The best visual acuity, visual field testing and color vision testing were available from the records in all these patients at different time points, i.e. before treatment and 1 month (+/-7 days), 3 months (+/-15 days), 6 months (+/-20 days) and 12 months (+/-30 days) after treatment. RESULTS: All patients showed active intraocular inflammation at their first visit. A decreased visual acuity, abnormality of color vision and abnormal visual field were observed at presentation. Visual acuity and color vision rapidly improved at 1 and 3 months and gradually improved thereafter. Visual field defects significantly improved at 6 months and gradually improved thereafter. However, visual field defects were still observed in 27.5% of the tested patients following a 12-month treatment. Color vision returned to the normal level only in about one-third of these patients at this time point. CONCLUSIONS: Visual function was severely impaired in VKH patients with active uveitis but rapidly improved following immunosuppressive therapy. Visual fields are much more severely affected by the disease than visual acuity and its improvement lagged behind that of visual acuity and color vision. PMID- 22297831 TI - Assessing the effects of chronic sazetidine-A delivery on nicotine self administration in both male and female rats. AB - RATIONALE: Sazetidine-A is a selective alpha4beta2 nicotinic receptor desensitizing agent and partial agonist. It has been shown in previous studies to significantly reduce nicotine self-administration in rats after acute or repeated injections. However, the effects of continuous chronic infusions of sazetidine-A on maintenance of nicotine self-administration and relapse after abstinence have yet to be examined. OBJECTIVES: This study evaluated the efficacy of continuous sazetidine-A infusions (sc) over a period of 4 weeks to reduce nicotine self administration in male and female Sprague-Dawley rats. METHODS: Sazetidine-A was administered via Alzet osmotic minipumps to young adult female and male rats at doses of 0, 2 or 6 mg/kg/day for 4 weeks. The effects of sazetidine-A on IV nicotine self-administration were examined in repeated 3-h sessions over the first 2 weeks of infusion followed by 1 week of forced abstinence from nicotine and 1 week of resumed nicotine access. RESULTS: The 6 mg/kg/day sazetidine-A dose significantly reduced overall nicotine self-administration compared with vehicle control across the sessions for both male (p < 0.001) and female (p < 0.05) rats. The lower 2 mg/kg/day sazetidine-A infusion dose was effective in reducing nicotine self-administration for male (p < 0.001), but not female rats. No attenuation in sazetidine-A effectiveness was seen over the course of the 4-week treatment. In the vehicle control group, male rats self-administered significantly (p < 0.001) more nicotine than females. CONCLUSIONS: The continuing effectiveness of sazetidine-A in reducing nicotine self-administration in both male and female rats supports its promise as a new treatment to help people successfully quit smoking. PMID- 22297832 TI - Combined usual and nodular types of vascular transformation of sinuses in the same lymph node. PMID- 22297833 TI - Metastatic mammary carcinoma with DCIS-like morphology: a report of two cases. AB - Two cases of breast carcinoma with lymph node metastases are presented. In each case the metastases demonstrated the unusual phenomenon of resembling either cribriform or comedo DCIS. Furthermore both cases had the additional rare feature of demonstrable lymphatic involvement by DCIS-like carcinoma. PMID- 22297835 TI - Pediatric surgical site infection in the developing world: a Kenyan experience. AB - BACKGROUND: The purpose of the current study was to determine the incidence of pediatric surgical site infections(SSIs) at an academic children's hospital in rural sub-Saharan Africa and to identify potentially modifiable risk factors. METHODS: Prospectively collected data from 1,008 surgical admissions to Bethany Kids Kijabe Hospital (Kijabe, Kenya) were analyzed retrospectively. Follow-up data were available in 940 subjects. RESULTS: SSIs occurred in 6.8% of included subjects(N = 64). Superficial (69%) and deep (29%) infections of the back (38%) and head (25%) were most common. When comparing children who developed SSI to those who did not, we found that wound contamination classification and duration of operation were the only variables with significant differences between groups. CONCLUSIONS: Our rate of SSI among pediatric patients insub-Saharan Africa is the lowest reported in the literature to date. More work is needed to identify modifiable risk factors for pediatric SSI in low- and middle-income countries. PMID- 22297836 TI - A review of patch options in the repair of congenital diaphragm defects. AB - Repair of congenital diaphragmatic hernia (CDH) continues to pose a dilemma for the pediatric surgeon. While the management of CDH has evolved from surgical urgency to delayed repair after medical optimization with substantial improvements in mortality, morbidity continues to perplex clinicians. Significant morbidity occurs with recurrence, re-recurrence and complications such as obstructions, principally with mesh repair. When primary closure is not possible, mesh repair is indicated. While there are several non-absorbable prosthetic, absorbable biosynthetic and composite mesh types available, the ideal mesh remains elusive. In this article, we reviewed the current materials, reported advantages, and animal and clinical studies of non-absorbable prosthetic, absorbable biosynthetic and composite mesh. However, adequate comparative data are lacking, leaving a wide void for future animal models and clinical studies. PMID- 22297837 TI - Effect of replacing soybean meal with cottonseed meal on growth, hematology, antioxidant enzymes activity and expression for juvenile grass carp, Ctenopharyngodon idellus. AB - An 8-week feeding trial was conducted to evaluate the effect of replacing soybean meal (SBM) with cottonseed meal (CSM) on growth and health of grass carp. Four isonitrogenous diets containing 0, 16.64, 32.73 and 48.94% of CSM, respectively, as replacements of 0, 35, 68 and 100% of SBM were fed to fish (initial body weight 7.14 +/- 0.75 g/fish) in triplicate aquaria twice daily. The results indicated that fish fed diet containing 16.64% CSM as a replacement of 35% of SBM was not affected in weight gain (WG), feed efficiency ratio (FER) and feed conversion ratio (FCR) (P>0.05), while fish fed diets containing higher level of dietary CSM (32.73 and 48.94%) significantly decreased WGand PER and significantly increased FCR (P<0.05). Fish fed diets containing 16.64% of CSM had significantly increased hematocrit (Ht) and hemoglobin (Hb) values compared with fish fed with other diets (P<0.05). The activity of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), gene expression levels of GSH Px and CAT, and content of malondialdehyde (MDA) were significantly lower for fish fed diets containing 16.64% CSM compared with fish fed other diets (P<0.05). These results showed 16.64% CSM could be used to replace 35% SBM in the diets of juvenile grass carp and without health impact. PMID- 22297838 TI - Review of HPLC methods and HPLC methods with mass spectrometric detection for direct determination of aspirin with its metabolite(s) in various biological matrices. AB - Aspirin, the most widely used drug in the world, has been known to mankind for over a century. It is not only the pharmacologically active entity, but is also biotransformed into a major metabolite, i.e. salicylic acid, which also exhibits similar pharmacologic/pharmacodynamic properties. Hence it is necessary to quantitate aspirin along with its metabolite(s) in various biological matrices accurately and precisely to correlate with pharmacological/pharmacodynamic activity. This paper provides a comprehensive overview of various bioanalytical methods (HPLC and LC-MS/MS) that have been reported for direct quantitation of aspirin along with its metabolite(s). The review also provides general information on sample collection, sample processing, internal standard selection, conditions for chromatographic separation, succinct validation data and applicable conclusions for reported assays in a structured manner. PMID- 22297839 TI - Adjuvant chemotherapy decreases and postpones distant metastasis in extremity stage IIB/III synovial sarcoma patients. AB - BACKGROUND AND OBJECTIVES: The role of adjuvant chemotherapy (AC) in treatment of synovial sarcoma remains controversial. Aim of our study is to investigate the influence of AC on disease-specific survival and metastasis free survival, the difference in time to metastasis (TTM) was also analyzed. MATERIALS AND METHODS: Seventy-six cases of stage IIB/III synovial sarcoma from January 1993 to December 2008 were retrospectively analyzed. All the 76 patients were treated with surgical resection. AC regimen included first line MAID or AIM, second line Gemcitabine + Docetaxel with sufficient dose intensity. The clinical, pathologic, and treatment variables were analyzed for disease specific survival (DSS), metastasis free survival (MFS) and TTM. RESULTS: Median follow up period was 68 months. 51 patients received AC (51/76, 67%), 25 received no adjuvant chemotherapy (NAC, 25/76, 33%). The 5-year DSS of the AC patients was 73%(58-87%) compared with 31%(19-52%) for the NAC patients (P = 0.001). AC was also independently associated with improved MFS (P = 0.008) and prolonged TTM (P = 0.001). CONCLUSIONS: Patients with stage IIB/III synovial sarcoma might benefit in DSS, MFS, and a prolonged TTM from AC. PMID- 22297840 TI - Higher cell stiffness indicating lower metastatic potential in B16 melanoma cell variants and in (-)-epigallocatechin gallate-treated cells. AB - PURPOSE: To understand how nanomechanical stiffness affects metastatic potential, we studied the relationship between cell migration, a characteristic of metastasis, and cell stiffness using atomic force microscopy (AFM), which can measure stiffness (elasticity) of individual living cells. METHODS: Migration and cell stiffness of three metastatic B16 melanoma variants (B16-F10, B16-BL6, and B16-F1 cells), and also effects of (-)-epigallocatechin gallate (EGCG), were studied using Transwell assay and AFM. RESULTS: Migration of B16-F10 and B16-BL6 cells was 3 and 2 times higher than that of B16-F1 cells in Transwell assay, and cell stiffness determined by AFM was also different among the three variants, although they have similar morphologies and the same growth rates: Means of Young's modulus were 350.8 +/- 4.8 Pa for B16-F10 cells, 661.9 +/- 16.5 Pa for B16-BL6 cells, and 727.2 +/- 13.0 Pa for B16-F1 cells. AFM measurements revealed that highly motile B16-F10 cells have low cell stiffness, and low motile and metastatic B16-F1 cells have high cell stiffness: Nanomechanical stiffness is inversely correlated with migration potential. Treatment of highly motile B16-F10 cells with EGCG increased cell stiffness 2-fold and inhibited migration of the cells. CONCLUSIONS: Our study with AFM clearly demonstrates that cell stiffness is a reliable quantitative indicator of migration potential, and very likely metastatic potential, even in morphologically similar cells. And increased cell stiffness may be a key nanomechanical feature in inhibition of metastasis. PMID- 22297841 TI - Clinical benefits of a new multipurpose disinfecting solution in silicone hydrogel and soft contact lens users. AB - OBJECTIVES: To evaluate the safety and efficacy of a new multipurpose disinfecting solution (MPDS) containing a diblock copolymer, poly(oxyethylene) poly(oxybutylene), designed to improve the wetting properties of silicone hydrogel lenses. METHODS: This 90-day, randomized, concurrently controlled, double-masked, multisite study involved 573 subjects at 30 investigational sites in the United states. Existing lens wearers were randomly assigned to either regimen 1 (OPTI-FREE PureMoist, a newly developed formulation, Alcon Laboratories Inc., Fort Worth, TX) or regimen 2 (renu fresh, Bausch and Lomb Inc., Rochester, NY). At baseline, days 7, 30, 60, and 90, the subjects recorded subjective evaluations relating to lens acceptability and comfort, wearing time, and rewetting drop frequency, whereas investigators assessed slitlamp findings (including corneal fluorescein staining), lens deposits (modified Rudko), visual acuity, and adverse events. Group IV lenses were collected for ex vivo measurement of lysozyme deposits. RESULTS: Differences favoring regimen 1 were noted on day 90 for subjective evaluations of lens comfort (insertion, removal, overall); lens moisture and freshness; gentle on eye; clear vision; and lens handling (all P<0.004). Corneal fluorescein staining severity and area and lysozyme deposits (group IV lenses) were lower with regimen 1 (P<0.0001). CONCLUSIONS: This 90-day study shows that the new MPDS designed for silicone hydrogel lenses is safe and effective when used by both silicone-hydrogel and traditional soft lens wearers. By improving comfort and decreasing lysozyme deposits and corneal fluorescein staining, the new MPDS enhances patients' wearing experience and helps maintain optimal lens performance. PMID- 22297842 TI - Nuclease cleavage-assisted target recycling for signal amplification of free label impedimetric aptasensors. AB - A simple, novel, label-free impedimetric aptasensor with signal amplification is developed for ultrasensitive detection of small molecules on a carbon nanotubes based sensing platform by combining target-induced release of the aptamers and nuclease cleavage-assisted target recycling. PMID- 22297843 TI - Emerging Therapeutic Targets in Diffuse Large B-Cell Lymphoma. AB - OPINION STATEMENT: The standard front-line treatment of Diffuse Large B-Cell Lymphoma (DLBCL) remains Rituximab combined with multi-agent cytotoxic chemotherapy. In spite of high response rates to this therapy, relapsed/refractory disease is observed in up to 40% of patients. It is our opinion that additional chemoimmunotherapy, followed by high-dose therapy with autologous stem cell transplant (HDT-ASCT) for responsive disease, is the optimal therapy for these patients. However, many patients cannot tolerate HDT-ASCT, or have relapsed/refractory disease in spite of it. These patients have a poor overall prognosis, and there is no clear consensus as to how these patients should be treated. Over the past decade, significant advances have been made in the understanding of the molecular genesis and subtyping of DLBCL, leading to the identification of multiple pathways and molecules that can be targeted for clinical benefit. Examples include Bcl-2, Bcl-6, cell surface markers, and myriad molecules in both the B-Cell receptor and PI3K/Akt/mTOR pathways. As agents targeting these molecules and pathways progress from preclinical models to early clinical trials, more is learned about what might predict for response to these agents, such as cell of origin classification, and/or expression of relevant molecular markers, as measured by immunohistochemistry or gene expression profiling. Both the successes and failures of these novel targeted agents promise to dramatically refine, improve, and individualize the classification and treatment of DLBCL. Therefore, it is our opinion that patients with relapsed/refractory DLBCL are an ideal population for clinical trials due to both the lack of standardized treatment, and the recent advancements in pathobiology and early-phase treatment options. PMID- 22297844 TI - Realization of three-qubit quantum error correction with superconducting circuits. AB - Quantum computers could be used to solve certain problems exponentially faster than classical computers, but are challenging to build because of their increased susceptibility to errors. However, it is possible to detect and correct errors without destroying coherence, by using quantum error correcting codes. The simplest of these are three-quantum-bit (three-qubit) codes, which map a one qubit state to an entangled three-qubit state; they can correct any single phase flip or bit-flip error on one of the three qubits, depending on the code used. Here we demonstrate such phase- and bit-flip error correcting codes in a superconducting circuit. We encode a quantum state, induce errors on the qubits and decode the error syndrome--a quantum state indicating which error has occurred--by reversing the encoding process. This syndrome is then used as the input to a three-qubit gate that corrects the primary qubit if it was flipped. As the code can recover from a single error on any qubit, the fidelity of this process should decrease only quadratically with error probability. We implement the correcting three-qubit gate (known as a conditional-conditional NOT, or Toffoli, gate) in 63 nanoseconds, using an interaction with the third excited state of a single qubit. We find 85 +/- 1 per cent fidelity to the expected classical action of this gate, and 78 +/- 1 per cent fidelity to the ideal quantum process matrix. Using this gate, we perform a single pass of both quantum bit- and phase-flip error correction and demonstrate the predicted first-order insensitivity to errors. Concatenation of these two codes in a nine-qubit device would correct arbitrary single-qubit errors. In combination with recent advances in superconducting qubit coherence times, this could lead to scalable quantum technology. PMID- 22297845 TI - Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. AB - Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and the leading cause of chronic liver disease in the Western world. Twenty per cent of NAFLD individuals develop chronic hepatic inflammation (non-alcoholic steatohepatitis, NASH) associated with cirrhosis, portal hypertension and hepatocellular carcinoma, yet the causes of progression from NAFLD to NASH remain obscure. Here, we show that the NLRP6 and NLRP3 inflammasomes and the effector protein IL-18 negatively regulate NAFLD/NASH progression, as well as multiple aspects of metabolic syndrome via modulation of the gut microbiota. Different mouse models reveal that inflammasome-deficiency associated changes in the configuration of the gut microbiota are associated with exacerbated hepatic steatosis and inflammation through influx of TLR4 and TLR9 agonists into the portal circulation, leading to enhanced hepatic tumour-necrosis factor (TNF)-alpha expression that drives NASH progression. Furthermore, co housing of inflammasome-deficient mice with wild-type mice results in exacerbation of hepatic steatosis and obesity. Thus, altered interactions between the gut microbiota and the host, produced by defective NLRP3 and NLRP6 inflammasome sensing, may govern the rate of progression of multiple metabolic syndrome-associated abnormalities, highlighting the central role of the microbiota in the pathogenesis of heretofore seemingly unrelated systemic auto inflammatory and metabolic disorders. PMID- 22297846 TI - Enhancer decommissioning by LSD1 during embryonic stem cell differentiation. AB - Transcription factors and chromatin modifiers are important in the programming and reprogramming of cellular states during development. Transcription factors bind to enhancer elements and recruit coactivators and chromatin-modifying enzymes to facilitate transcription initiation. During differentiation a subset of these enhancers must be silenced, but the mechanisms underlying enhancer silencing are poorly understood. Here we show that the histone demethylase lysine specific demethylase 1 (LSD1; ref. 5), which demethylates histone H3 on Lys 4 or Lys 9 (H3K4/K9), is essential in decommissioning enhancers during the differentiation of mouse embryonic stem cells (ESCs). LSD1 occupies enhancers of active genes that are critical for control of the state of ESCs. However, LSD1 is not essential for the maintenance of ESC identity. Instead, ESCs lacking LSD1 activity fail to differentiate fully, and ESC-specific enhancers fail to undergo the histone demethylation events associated with differentiation. At active enhancers, LSD1 is a component of the NuRD (nucleosome remodelling and histone deacetylase) complex, which contains additional subunits that are necessary for ESC differentiation. We propose that the LSD1-NuRD complex decommissions enhancers of the pluripotency program during differentiation, which is essential for the complete shutdown of the ESC gene expression program and the transition to new cell states. PMID- 22297847 TI - Serotonin accumulation in transgenic rice by over-expressing tryptophan decarboxylase results in a dark brown phenotype and stunted growth. AB - A mutant M47286 with a stunted growth, low fertility and dark-brown phenotype was identified from a T-DNA-tagged rice mutant library. This mutant contained a copy of the T-DNA tag inserted at the location where the expression of two putative tryptophan decarboxylase genes, TDC-1 and TDC-3, were activated. Enzymatic assays of both recombinant proteins showed tryptophan decarboxylase activities that converted tryptophan to tryptamine, which could be converted to serotonin by a constitutively expressed tryptamine 5' hydroxylase (T5H) in rice plants. Over expression of TDC-1 and TDC-3 in transgenic rice recapitulated the stunted growth, darkbrown phenotype and resulted in a low fertility similar to M47286. The degree of stunted growth and dark-brown color was proportional to the expression levels of TDC-1 and TDC-3. The levels of tryptamine and serotonin accumulation in these transgenic rice lines were also directly correlated with the expression levels of TDC-1 and TDC-3. A mass spectrometry assay demonstrated that the darkbrown leaves and hulls in the TDC-overexpressing transgenic rice were caused by the accumulation of serotonin dimer and that the stunted growth and low fertility were also caused by the accumulation of serotonin and serotonin dimer, but not tryptamine. These results represent the first evidence that over expression of TDC results in stunted growth, low fertility and the accumulation of serotonin, which when converted to serotonin dimer, leads to a dark brown plant color. PMID- 22297848 TI - [Immune mechanisms in retinal degeneration]. AB - Hereditary retinal dystrophies are characterised by a common apoptotic pathway leading to progressive retinal degeneration. Similar degenerative processes are evident in multifactorial and complex retinal disorders including age-related macular degeneration. To understand early triggers of these mechanisms, genetic and experimental mouse models have been developed that mimic various forms of human retinal degeneration. In most of these models, early chronic activation of the innate immune system has been documented. This process mainly involves the complement cascade as humoral component and microglial cells as sensors and effectors of the retinal immune response. Current evidence suggests that the genetic predisposition and individual factors like age or diet critically influence the immune homeostasis in the retina. Based on their effectiveness, innate immune mechanisms are thought to support or even provoke retinal degeneration. This review article summarises recent progress in understanding the role of innate immunity in retinal degenerative diseases. We especially focus on human studies and attempt to provide a link between activation of the complement system and microglial function. Moreover, concepts are presented that highlight the retinal immunopathology as potential therapeutic target to prevent vision loss. PMID- 22297849 TI - [The end of the "democratic ophthalmology" in the German Empire (1928-1933)]. PMID- 22297850 TI - [Combined phacoemulsification with trabecular aspiration with differing outcomes in pseudoexfoliative glaucoma - a retrospective study]. AB - INTRODUCTION: The aim of this study was to differentiate the pressure-reducing results following trabecular aspiration combined with small incision cataract surgery in eyes with pseudoexfoliation depending on preoperative pressure and medication score. PATIENTS AND METHODS: A retrospective analysis was made of 104 exfoliative eyes of 104 patients who underwent combined phaco/trabecular aspiration. Success was defined as a relative reduction of IOP of at least 20 %, absolute IOP of <= 20 mmHg, stable or reduced medication score and a lack of any further pressure-reducing surgery. RESULTS: The success rate was 0.68 and 0.64 after 1 and 2 years. In eyes with medically uncontrolled preoperative IOP (> 20 mmHg) the IOP dropped significantly from 25.4 +/- 4.3 mmHg to 17.0 +/- 3.4 mmHg after two years. In eyes with preoperative controlled IOP the pressure lowering effect was low (17.1 +/- 2.3 to 15.9 +/- 2.3 mmHg) with a significant reduction of medication. CONCLUSIONS: Combined cataract surgery and trabecular aspiration is a reasonable option in exfoliative eyes with IOP values in the low twenties in order to achieve a reduction of topical medications and to reach a stable IOP level. PMID- 22297851 TI - Modified yeast-two-hybrid system to identify proteins interacting with the growth factor progranulin. AB - Progranulin (PGRN), also known as granulin epithelin precursor (GEP), is a 593 amino-acid autocrine growth factor. PGRN is known to play a critical role in a variety of physiologic and disease processes, including early embryogenesis, wound healing, inflammation, and host defense. PGRN also functions as a neurotrophic factor, and mutations in the PGRN gene resulting in partial loss of the PGRN protein cause frontotemporal dementia. Our recent studies have led to the isolation of PGRN as an important regulator of cartilage development and degradation. Although PGRN, discovered nearly two decades ago, plays crucial roles in multiple physiological and pathological conditions, efforts to exploit the actions of PGRN and understand the mechanisms involved have been significantly hampered by our inability to identify its binding receptor(s). To address this issue, we developed a modified yeast two-hybrid (MY2H) approach based on the most commonly used GAL4 based 2-hybrid system. Compared with the conventional yeast two-hybrid screen, MY2H dramatically shortens the screen process and reduces the number of false positive clones. In addition, this approach is reproducible and reliable, and we have successfully employed this system in isolating the binding proteins of various baits, including ion channel, extracellular matrix protein, and growth factor. In this paper, we describe this MY2H experimental procedure in detail using PGRN as an example that led to the identification of TNFR2 as the first known PGRN-associated receptor. PMID- 22297852 TI - Tracking a therapeutic response: how reliable are serial measurements of LV perfusion and function? PMID- 22297853 TI - The effect of caffeine on adenosine myocardial perfusion imaging: time to reassess? PMID- 22297855 TI - Some people and places important in the history of analytical chemistry in Serbia. PMID- 22297854 TI - The initial step of silicate versus aluminosilicate formation in zeolite synthesis: a reaction mechanism in water with a tetrapropylammonium template. AB - The initial step for silicate and aluminosilicate condensation is studied in water in the presence of a realistic tetrapropylammonium template under basic conditions. The model corresponds to the synthesis conditions of ZSM5. The free energy profile for the dimer formation ((OH)(3)Si-O-Si-(OH)(2)O(-) or [(OH)(3)Al O-Si-(OH)(3)](-)) is calculated with ab initio molecular dynamics and thermodynamic integration. The Si-O-Si dimer formation occurs in a two-step manner with an overall free energy barrier of 75 kJ mol(-1). The first step is associated with the Si-O bond formation and results in an intermediate with a five-coordinated Si, and the second one concerns the removal of the water molecule. The template is displaced away from the Si centres upon dimer formation, and a shell of water molecules is inserted between the silicate and the template. The main effect of the template is to slow down the backward hydrolysis reaction with respect to the condensation one. The Al-O-Si dimer formation first requires the formation of a metastable precursor state by proton transfer from Si(OH)(4) to Al(OH)(4)(-) mediated by a solvent molecule. It then proceeds through a single step with an overall barrier of 70 kJ mol(-1). The model with water molecules explicitly included is then compared to a simple calculation using an implicit continuum model for the solvent. The results underline the importance of an explicit and dynamical treatment of the water solvent, which plays a key role in assisting the reaction. PMID- 22297856 TI - Miniaturized extraction methods of triclosan from aqueous and fish roe samples. Bioconcentration studies in zebrafish larvae (Danio rerio). AB - Triclosan, an antibacterial and antifungal agent, is widely used in household and personal care products, processed foods and food packaging, etc., and thus also released into the environment. Triclosan is acutely and chronically toxic to aquatic organisms and bioaccumulates in fish tissue. Here, we propose a new miniaturized triclosan extraction method for aqueous and fish roe samples, based on the use of a vortex mixer and an ultrasonic probe, respectively, and useful for triclosan determination by gas chromatography coupled to a micro electron capture detector. Different solvents for extraction and sorbents for clean-up purposes were tested. Multivariate optimization of the variables affecting ultrasonic extraction (ultrasound radiation amplitude, sonication time, sample temperature, and the ratio of sample amount and extracting volume) was carried out. Solvent extraction using ethyl acetate and further clean-up with mixed bed cartridges with two layers of Florisil(r) and Florisil(r) impregnated with 10% sulfuric acid only for fish roe samples was finally selected. Extraction efficiencies of up to 95% and 90%, and detection limits of 0.165 ng ml(-1) and 2.7 ng g(-1) for aqueous and fish roe samples were obtained, respectively. The optimized method was used in bioconcentration studies with zebrafish larvae (Danio rerio), as an alternative method to the Organization for Economic Cooperation and Development technical guideline 305. Bioconcentration values, BCF = 2,630 and 2,018 at exposure concentrations of 30 and 3 MUg L(-1), respectively, were assessed. These results are in agreement with those reported in the literature, showing the feasibility of the method for estimation of toxicokinetic parameters and bioconcentration factors using zebrafish larvae instead of adult fishes, reducing considerable animal testing, as suggested by the European legislation. PMID- 22297857 TI - Comparative evaluation of three methods based on high-performance liquid chromatography analysis combined with a 2,2'-diphenyl-1-picrylhydrazyl assay for the rapid screening of antioxidants from Pueraria lobata flowers. AB - Traditional activity-guided fractionation of natural products is a time consuming, labor intensive, and expensive strategy, which cannot compete with high-throughput and rapid screening of natural products. Therefore, more efficient approaches are necessary for searching active compounds from natural products. Three main methods based on high-performance liquid chromatography (HPLC) analysis combined with 2,2'-diphenyl-1-picrylhydrazyl (DPPH) assay, DPPH spiking HPLC analysis, on-line post-column HPLC-DPPH analysis, and HPLC-based DPPH activity profiling, were then developed for the rapid screening of antioxidants from complex mixtures. In the present study, a comparative study of these three methods has been conducted to identify antioxidants from an ethyl acetate fraction of Pueraria lobata flowers. The parameters in HPLC analysis and DPPH assay were optimized. The results indicated that all three methods could achieve similar information with regard to antioxidants, without the need for preparative isolation techniques. However, there were differences in instrumental set-up, sensitivity, and efficiency. DPPH spiking HPLC analysis seemed to be more sensitive and effective with simpler instrumental set-up and easier operation, which could also detect the total antioxidant capacity of color complexes. Eighteen antioxidants were tentatively screened and identified from P. lobata flowers by DPPH spiking HPLC-MS/MS. Among them, ten compounds including one new compound were first isolated from P. lobata flowers, and the DPPH radical scavenging activity of the new compound was reported for the first time. PMID- 22297858 TI - A label-free electrochemical DNA biosensor based on a Zr(IV)-coordinated DNA duplex immobilised on a carbon nanofibre|chitosan layer. AB - A label-free electrochemical biosensor for detecting DNA hybridisation was developed by monitoring the change in the voltammetric activity of ferrocenecarboxylic acid at the biosensor-solution interface. The biosensor was constructed by initially immobilising on a glassy carbon electrode an anchoring layer consisting of chitosan, carboxyl group functionalised carbon nanofibres and glutaraldehye. Chitosan acted as an adhering agent and carbon nanofibres were strategically used to provide a large surface area with binding points for DNA immobilisation, while glutaraldehye was a linker for DNA probes on the electrode surface. Based on a two-factorial design, cyclic voltammetry of [Fe(CN)(6)](3-/4 ) was performed to optimise the composition of the anchoring layer.Next, a 17 base pair DNA probe was attached to the anchoring layer, followed by its complementary target. Zr(IV) ion, known to exhibit affinity for oxygen-containing electroactive markers, for example, ferrocenecarboxylic acid, was then coordinated in the DNA duplex. In this way, ferrocenecarboxylic acid was attracted towards the biosensor for oxidation. A change in the voltammetric oxidation current of ferrocenecarboxylic acid pre- and post-hybridisation was used to provide an indication of hybridisation. A linear dynamic range between 0.5 and 40 nM and a detection limit of 88 pM of DNA target were then achieved. In addition, the biosensor exhibited good selectivity, repeatability and stability for the determination of DNA sequences. PMID- 22297859 TI - Probe functionalization with a Rhop-3 antibody: toward a Rhop-3 antigen immunosensor for detection of malaria. AB - The antibody specific for the malaria protein, Rhop-3, and FL-Rhop-3, were immobilized on the surface of a gold electrode modified with cysteamine. Colloidal gold was used to enhance the detection signal for Rhop-3 antigens. The Rhop-3 antibody was also immobilized on gold electrodes preactivated with dithiobis(succinimidyl proprionate) (DSP). Immobilization was performed at room temperature and at 37 degrees C. Cyclic voltammetry (CV) was used to monitor the interaction between the immobilized antibody and its cognate antigen in solution, using ferricyanide, K3Fe(CN)6, as reporting electroactive probe. Tests indicate recognition of Rhop-3 protein by the immobilized antibody. Antigen recognition was enhanced by incubation at 37 degrees C compared with room-temperature incubation. Our results suggest that an immunosensor can be developed and optimized to aid detection of Rhop-3 antigens in samples from malaria patients. As far as we are aware, this is the first amperometric immunosensor targeting Rhop-3 antigen as a malaria biomarker. PMID- 22297860 TI - Applications of peptide nucleic acids (PNAs) and locked nucleic acids (LNAs) in biosensor development. AB - Nucleic acid biosensors have a growing number of applications in genetics and biomedicine. This contribution is a critical review of the current state of the art concerning the use of nucleic acid analogues, in particular peptide nucleic acids (PNA) and locked nucleic acids (LNA), for the development of high performance affinity biosensors. Both PNA and LNA have outstanding affinity for natural nucleic acids, and the destabilizing effect of base mismatches in PNA- or LNA-containing heterodimers is much higher than in double-stranded DNA or RNA. Therefore, PNA- and LNA-based biosensors have unprecedented sensitivity and specificity, with special applicability in DNA genotyping. Herein, the most relevant PNA- and LNA-based biosensors are presented, and their advantages and their current limitations are discussed. Some of the reviewed technology, while promising, still needs to bridge the gap between experimental status and the harder reality of biotechnological or biomedical applications. PMID- 22297862 TI - Intraoperative blood pressure changes as a risk factor for anastomotic leakage in colorectal surgery. AB - PURPOSE: Anastomotic leakage is a serious complication after colorectal surgery. Pre- and intraoperative factors may contribute to failure of colorectal anastomosis. In this study we have tried to determine risk factors for anastomotic leakage, with special emphasis on intraoperative blood pressure changes. METHODS: During a 24-month period, patients receiving a colorectal anastomosis were prospectively evaluated. For each patient preoperative characteristics, intraoperative adverse events and surgical outcome data were collected. Blood pressure changes were calculated as a relative decrease (>25% and >40%) from preoperative baseline values. RESULTS: During the study period, 285 patients underwent colorectal surgery with an anastomosis. Fifteen patients developed an anastomotic leakage (5.3%). All patients who developed a leakage had a left-sided procedure (P < 0.001). When blood loss was more than 250 mL (P = 0.003) or an intraoperative adverse event occurred (P = 0.050), the risk for developing an anastomotic leakage was significantly increased. A preoperative high diastolic blood pressure of >=90 mmHg (P = 0.008) and severe intraoperative hypotension [>40% decrease in diastolic blood pressure (P = 0.049)] were identified as univariate risk factors for anastomotic leakage. CONCLUSIONS: The development of an anastomotic leakage after colorectal surgery is related to surgical, patient and anaesthetic risk factors. A high preoperative diastolic blood pressure and profound intraoperative hypotension combined with complex surgery, marked by a blood loss of >=250 mL and the occurrence of intraoperative adverse events, is associated with an increased risk of developing anastomotic leakage. PMID- 22297863 TI - The risk of advanced histology in small-sized colonic polyps: are non-invasive colonic imaging modalities good enough? AB - PURPOSE: The study aims to evaluate the risk of advanced histology within small colonic polyps and assess whether this risk warrants different recommendation for surveillance and treatment of such polyps. METHODS: A retrospective study of all patients undergoing their first ever colonoscopy and polypectomy in a tertiary hospital for one of three indications: screening, positive family history,and positive occult blood in stool. The histological reports of all resected polyps were retrieved and stratified according to the various polyps' sizes. Advanced neoplasia was defined as tubular adenoma >=10 mm or any size polyp with advanced histology, i.e., villous or tubulovillous adenoma, high-grade dysplasia, intramucosal carcinoma, or invasive cancer. RESULTS: Seven hundred forty-one patients who had a total of1,192 resected polyps were included. Of polyps <=5 mm in size, 1.6% harbored invasive cancer or high-grade dysplasia,and additional 4.1% contained villous component. The rate of advanced histology for polyps sized 6-9 mm was over 15%. The rate of advanced histology in polyps <=5 mm was not significantly different when employing sensitivity analysis accounting for possible under or overestimation of polyp sizes by 1 and 2 mm. However, 4.6% of polyps sized 6-9 mm were found to harbor an invasive or high-grade dysplasia component when taken into account a 2-mm overestimation. CONCLUSIONS: A non negligible fraction of small polyps harbor advanced histology. This finding suggests that expectant follow-up by non-invasive colonic imaging modalities for small polyps or not reporting them may put more than 5% of patients at risk of dysplasia progression. PMID- 22297864 TI - Competence and sporulation factor derived from Bacillus subtilis improves epithelial cell injury in intestinal inflammation via immunomodulation and cytoprotection. AB - INTRODUCTION: Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. These probiotic effects are considered to be displayed through the mediation of effective molecules derived from these bacteria because live bacteria as well as their conditioned media exhibit beneficial effects in many cases. However, many of the probiotic-derived molecules which mediate such benefits have so far been poorly characterized. We previously found that competence and sporulation factor (CSF) activates the Akt and p38 MAPK pathways and protects epithelial cells from oxidant stress in the mammalian intestine. The purpose of this study is to determine the CSF effect on reducing intestinal inflammation. METHODS AND RESULTS: A protein array demonstrated that CSF induced the anti-inflammatory cytokine, IL-10, and decreased the release of pro-inflammatory mediators, IL-4, IL-6 and CXCL-1, induced by TNF-alpha in Caco2/bbe cells. CSF also induced the cytoprotective protein Hsp 27 in Caco2/bbe cells. The histological score of intestinal inflammation in 2% dextran sodium sulfate (DSS)-treated mice with the administration of 10 nM CSF was significantly lower than that of control mice. CSF also improved the survival rate of mice treated with a lethal concentration of DSS. CONCLUSION: Therefore, CSF is a potentially effective treatment for intestinal inflammation. PMID- 22297865 TI - Accuracy of transrectal ultrasound after preoperative radiochemotherapy compared to computed tomography and magnetic resonance in locally advanced rectal cancer. AB - INTRODUCTION: The aim of the present study was to compare the restaging results obtained by transrectal ultrasound (TRUS), computed tomography (CT), and magnetic resonance imaging (MRI) performed after preoperative chemoradiation with pathologic staging of the operative specimen. METHODS: From January 2008 to December 2009, all the consecutive patients with locally advanced rectal cancer that underwent neoadjuvant therapy at our department were evaluated. The results of diagnostic examinations and the definitive pathological examination were considered and compared. RESULTS: Thirty-seven patients were included in the study (27 males, 73%), mean age was 65.5 years (range 45-82 years). In all the patients TRUS and CT and in 20 patients MRI were performed before and after the treatment. Concerning the depth of invasion after treatment TRUS agreed with histopathology in 25/37 patients (67.5%), CT agreed in 22/ 37 cases (59.5%), and MRI in 12/20 cases (60%). Considering only neoplasia with stage T3, TRUS agreed in 23/24 cases (96%), CT in 19 cases (79%), and MRI in 10/12 cases (83.5%). Considering the tumors that did not exceed the rectal wall (T0, T1, and T2), TRUS agreed with histology in 2/13 cases (15.5%),CTin 3/13 cases (23%), andMRI 2/8 cases (25%). Concerning the presence of positive lymph nodes TRUS agreed with histology in 28/37 cases (75.5%), while CT agreed in 21/37 cases (56.5%) and MRI in 11/20 cases (55%). The concordance between the techniques was found to be low. CONCLUSIONS: Transrectal ultrasonography resulted as the most accurate method to determine neoplastic wall infiltration and lymph node involvement even after radiochemotherapy. In most cases, considering the poor correlation between the diagnostic procedures and the disagreement of the results, a restaging performed only with TRUS could be proposed, limiting the use of the other imaging methods to selected cases. PMID- 22297867 TI - Walking and examining the patient before running to the imaging tests. PMID- 22297866 TI - Polyp surveillance after surgery for colorectal cancer. AB - PURPOSE: Although it is known that those patients who have developed colorectal cancer (CRC) are at a higher risk to develop metachronous adenoma or CRC, no study has been performed to analyze the relationship between the risk factors and the time course for the formation of postoperative adenoma using survival analysis. METHODS: One hundred seventy-six patients with CRC,who had received surgical resection, were endoscopically followed-up to detect the development of metachronous adenoma or adenocarcinoama. The association between the risk factors such as age, synchronous adenomas with index CRC or other clinicopathological variables and the formation of postoperative adenoma was assessed using the logrank test and the Cox proportional hazard model. RESULTS: Age over 60, synchronous lesions at the time of surgery for primary CRCs and presence of diabetes mellitus(DM) as the associated disease were positively related to the formation of postoperative adenoma. Among those patients with the three risk factors, only 27.8% remained adenoma-free during 5 years after operation, whereas in the group without any risk factor, it was 90.4%. CONCLUSIONS: From our data, age over 60, synchronous adenomas or CRCs and DM were the potential risk factors for the postoperative formation of adenoma or CRC, and they should be taken into consideration when defining the appropriate interval of postoperative colonoscopy. PMID- 22297868 TI - Mortality rates due to amyotrophic lateral sclerosis in Sao Paulo City from 2002 to 2006. AB - OBJECTIVE: To describe the mortality rates of amyotrophic lateral sclerosis (ALS) in the city of Sao Paulo as a function of demographics, year, and region. METHOD: This was a retrospective descriptive study. Information was obtained from death certificates registered at the Program for the Improvement of Mortality Information, Municipal Health Department (PRO-AIM/SMS), coded as G12.2 according to International Classification of Diseases (ICD-10), from 2002 to 2006. RESULTS: Over the studied time, were found 326 deaths (51.6% women, overall mean age of 64.1 years). Highest deaths percentages happened in those from 60 to 69 and 70 to 79 years and in white individuals. ALS mortality rates ranged 0.44/100,000 in 2002 and 0.76/100,000 in 2006. No significant changes overtime in administrative districts were found. CONCLUSION: ALS mortality rates in Sao Paulo were lower in comparison to other countries, however any risk factor in our environment, lifestyle or genetic characteristics were found. PMID- 22297869 TI - Epidemiology of amyotrophic lateral sclerosis patients in a centre in Buenos Aires. AB - Sporadic amyotrophic lateral sclerosis (sALS) is considered a multifactorial disease with genetic and environmental factors causing motor neuron degeneration. OBJECTIVE: To describe the epidemiological and occupational characteristics of patients with sALS who attended the Ramos Mejia Hospital at Buenos Aires, Argentina. METHOD: We analyzed the medical records of sALS patients diagnosed between 2001 and 2008. All occupations were coded according to the International Standard Classification of Occupation (ISCO). RESULTS: 187 patients were assessed, 38.5% were women and 61.5% men. Mean age at diagnosis was 55 years. 16% of them came from rural areas; 68% of the studied population had no health insurance. 40% were employed in elementary occupations, 19 were technicians and 8 handicraftsmen. CONCLUSION: The most represented profession was elementary occupation. A large proportion of patients came from rural areas, which might suggest an increased risk of environmental exposure to an unknown agent in those regions. PMID- 22297870 TI - Alzheimer's disease qEEG: spectral analysis versus coherence. Which is the best measurement? AB - There is evidence in electroencephalography that alpha, theta and delta band oscillations reflect cognitive and memory performances and that quantitative techniques can improve the electroencephalogram (EEG) sensitivity. This paper presents the results of comparative analysis of qEEG variables as reliable markers for Alzheimer's disease (AD). We compared the sensitivity and specificity between spectral analysis (spectA) and coherence (Coh) within the same group of AD patients. SpectA and Coh were calculated from EEGs of 40 patients with mild to moderate AD and 40 healthy elderly controls. The peak of spectA was smaller in the AD group than in controls. AD group showed predominance of slow spectA in theta and delta bands and a significant reduction of inter-hemispheric Coh for occipital alpha 2 and beta 1 and for frontal delta sub-band. ROC curve supported that alpha band spectA was more sensitive than coherence to differentiate controls from AD. PMID- 22297871 TI - Alzheimer's disease: relationship between cognitive aspects and power and coherence EEG measures. AB - OBJECTIVE: To evaluate the relationship between specific cognitive aspects and quantitative EEG measures, in patients with mild or moderate Alzheimer's disease (AD). METHOD: Thirty-eight AD patients and 31 controls were assessed by CERAD neuropsychological battery (Consortium to Establish a Registry for AD) and the electroencephalogram (EEG). The absolute power and coherences EEG measures were calculated at rest. The correlations between the cognitive variables and the EEG were evaluated. RESULTS: In the AD group there were significant correlations between different coherence EEG measures and Mini-Mental State Examination, verbal fluency, modified Boston naming, word list memory with repetition, word list recall and recognition, and constructional praxis (p<0.01). These correlations were all negative for the delta and theta bands and positive for alpha and beta. There were no correlations between cognitive aspects and absolute EEG power. CONCLUSION: The coherence EEG measures reflect different forms in the relationship between regions related to various cognitive dysfunctions. PMID- 22297872 TI - Anxiety and depressive symptoms in clinically isolated syndrome and multiple sclerosis. AB - Depression and anxiety have been reported in patients with multiple sclerosis (MS) and in patients with clinically isolated syndrome (CIS). However, the precise mechanisms that lead to depressive and anxiety symptoms in these patients are still unclear. In this study we evaluated with the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI) patients with MS and CIS and compared them to controls. We also correlated BDI and BAI scores with clinical parameters. Kruskall-Wallis followed by Dunn's Multiple Comparison Test, Chi-square and Spearman test were used. Patients with MS had higher depressive and anxiety scores than controls. The BDI and BAI scores of patients with CIS were not significantly different from controls. There was a positive correlation between BDI, BAI and EDSS. Our results corroborate the view that MS patients have higher depression and anxiety levels than control subjects. Anxiety and depressive symptoms also seem to progress according to the severity of the disease. PMID- 22297873 TI - Assessment of cognition using the Rao's Brief Repeatable Battery of Neuropsychological Tests on a group of Brazilian patients with multiple sclerosis. AB - To assess the cognition of patients with multiple sclerosis (MS) using the Rao's Brief Repeatable Battery of Neuropsychological Tests (BRB-N). METHOD: BRB-N was translated and adapted for control subjects. Subsequently, it was applied to a group of patients with relapsing-remitting (RR) MS. RESULTS: The assessment on the healthy controls (n=47) showed that the correlation between tests on the same cognitive domain was high and that there was a five-factor solution that explained 90% of the total variance. Except for the Word List Generation subset of tests, the performance of patients with RRMS (n=39) was worse than that of the healthy controls. CONCLUSION: BRB-N is a relatively simple method to assess cognition of patients with MS in the daily clinic. It does not take long to apply and does not require special skills or equipment. PMID- 22297874 TI - Transcranial sonography as a diagnostic tool for Parkinson's disease: a pilot study in the city of Rio de Janeiro, Brazil. AB - In Brazil there is no systematic study on Transcranial Sonography (TCS), a neuroimaging method that depicts echogenic deep brain structures using ultrasound. OBJECTIVE: To establish the percentage of subjects with permissive temporal windows and to address the ability of TCS of the substantia nigra (SN) to distinguish parkinsonian patients in a Brazilian sample. METHOD: We performed TCS using the Acuson X300 (Siemens, Germany) in 37 individuals: 23 with Parkinson's disease (PD) and 14 healthy controls. RESULTS: 10.8% of subjects had insufficient temporal acoustic bone windows. SN echogenic areas were larger in patients (mean +/- SD, 0.31 +/- 0.08 cm(2)) compared to controls (mean +/- SD, 0.17 +/- 0.02 cm(2)). TCS accurately identified 88.2% of PD patients. CONCLUSION: A large proportion of Brazilians seem to be eligible for TCS. An expressive number of PD patients could be diagnosed by TCS based on an expanded SN echogenic area. However, the current data is preliminary and must be corroborated by larger studies. PMID- 22297875 TI - Temporomandibular disorders in patients with craniocervical dystonia. AB - Temporomandibular disorders are a set of musculoskeletal dysfunctions within the masticatory system, with multiple etiologies. OBJECTIVE: Since craniocervical dystonia can involve the same neuromuscular structure as the temporomandibular joint, we sought to assess the correlation between temporomandibular disorders and craniocervical dystonia. METHOD: We applied the Research Diagnostic Criteria for Temporomandibular Disorders to 42 patients with craniocervical dystonia, in order to identify orofacial pain and temporomandibular characteristics on the day of botulinum toxin injection. RESULTS: Twenty-two patients (52.3%) reported temporomandibular joint pain; 24 (57.1%), joint sounds; 20 (47.6%), masticatory muscle pain; and 21 (50%), diminished jaw mobility. The patients with oromandibular dystonia presented temporomandibular disorders more frequently than did patients with other types of craniocervical dystonia (p<0.001). CONCLUSION: Temporomandibular disorders occur frequently in patients with oromandibular dystonia. Further studies should address the proper treatment of temporomandibular disorders associated with dystonia. PMID- 22297876 TI - Quality of life in individuals with cervical dystonia before botulinum toxin injection in a Brazilian tertiary care hospital. AB - OBJECTIVE: The purpose of this study was to evaluate quality of life (QoL) in a Brazilian population of individuals with cervical dystonia (CD) without effect of botulinum toxin (BTx) or with only residual effect of BTx, and identify possible physical and social aspects that affect their QoL. METHOD: Sixty five out of sixty seven consecutive patients with CD were assessed with two instruments: Short-form Health Survey with 36 questions (SF-36) and Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). RESULTS: Severity of CD (TWSTRS) correlated moderately with two SF-36 subscale: role-physical (r= -0.42) and body pain (r= 0.43). Women also scored worse in two subscale of SF-36: vitality (p<0.05) and mental-health (p<0.005). CONCLUSION: Severity of CD and gender (female) were the main factors related to a worse QoL perception. These findings may help health professionals to predict which characteristics could lead to worse QoL, and therefore, better target their interventions to lessen the burden caused by CD. PMID- 22297877 TI - Intravenous thrombolysis is more effective in ischemic cardioembolic strokes than in non-cardioembolic? AB - It was suggested that intravenous thrombolysis (IT) leads to larger extent recanalization in cardioembolic stroke. In this work we assess if this has beneficial clinical traduction. METHOD: We evaluated 177 patients undergoing IT, which were categorized into cardioembolic (CE) and non-cardioembolic (NCE). National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale were compared. RESULTS: The mean age was 67.4 +/- 12.01 and 53.8% were male. The mean NIHSS was: 14 (admission), 9 (24 h) and 6 (discharge), similar in subgroups. The difference between NIHSS at admission and 24 hours was 4.17 +/- 4.92 (CE: 4.08 +/ 4.71; NCE: 4.27 +/- 5.17, p=0.900) and at admission and discharge there was an average difference of 6.74 +/- 5.58 (CE: 6.97 +/- 5.68; NCE: 6.49 +/- 5.49, p=0.622). The mRS at discharge and 3 months was not significantly different by subtype, although individuals whose event was NCE are more independent at 3 months. CONCLUSION: Ours findings argue against a specific paper of IT in CE. It can result from heterogeneity of NCE group. PMID- 22297878 TI - Fisher revised scale for assessment of prognosis in patients with subarachnoid hemorrhage. AB - The Fisher revised scale (FRS) presents an alternative for evaluating patients with subarachnoid hemorrhage (SAH). In this study, we compared the prognosis of patients with SAH and vasospasms (VSP). METHOD: This was a prospective study on patients with a diagnosis of aneurysmal SAH, 72 hours after the initial event. Sequential neurological examinations and Hunt and Hess (HaH) score were performed on the 1(st), 7(th) and 14(th) days. Transcranial Doppler was used to assess vasospasms. RESULTS: Out of the 24 patients studied, ten (41.66%) presented a delayed neurological deficit, such as diminished consciousness, decreased HaH score or death. The single patient classified as FS-1 did not have any delayed neurological deficit, while such deficits evolved in one patient out of five with FS-2 (20%); two out of seven with FS-3 (28.57%) and seven out of 11 with FS-4 (63.63%). CONCLUSION: Level three of the FS and FRS seemed to be compatible with regard to predicting the likelihood of progression to severe VSP. PMID- 22297879 TI - Neuroimaging in stroke and non-stroke pusher patients. AB - Pusher behavior (PB) is a disorder of postural control affecting patients with encephalic lesions. This study has aimed to identify the brain substrates that are critical for the occurrence of PB, to analyze the influence of the midline shift (MS) and hemorrhagic stroke volume (HSV) on the severity and prognosis of the PB. We identified 31 pusher patients of a neurological unit, mean age 67.4 +/ 11.89, 61.3% male. Additional neurological and functional examinations were assessed. Neuroimaging workup included measurement of the MS, the HSV in patients with hemorrhagic stroke, the analysis of the vascular territory, etiology and side of the lesion. Lesions in the parietal region (p=0.041) and thalamus (p=0.001) were significantly more frequent in PB patients. Neither the MS nor the HSV were correlated with the PB severity or recovery time. PMID- 22297880 TI - Psychiatry disorders and dengue: is there a relationship? AB - OBJECTIVE: The aim of this study was to examine the relationship of compulsive hoarding with dengue. METHOD: Fifty two adults notified by health vigilance authorities because of inappropriate trash accumulation in vacant lots in Goiania, Central Brazil, completed a questionnaire regarding the presence and severity of hoarding behavior (Hoarding Rating Scale-Interview HRS-I). Five dimensions of hoarding are evaluated with this instrument: difficulty using spaces due to clutter, difficulty discarding possessions, excessive acquisition of objects, emotional distress and functional impairment due to hoarding behaviors. RESULTS: The sample was primarily male, with an average age of 49 years. Eighty six percent of the sample scored 14 or greater on the HRS-I, indicating pathological hoarding. The medias of the five HRS-I domains were high, indicating severeness of all dimentions of pathological hoarding. CONCLUSION: These results highlight the relationship between psychiatric disorder and actions upon environmental conditions that favors dengue, as well as its associated public health burden. PMID- 22297881 TI - Risk and determinant factors for obstructive sleep apnea in patients with epilepsy. AB - OBJECTIVE: To evaluate the prevalence of risk of having obstructive sleep apnea (OSA) and its determinants in patients with epilepsy (PE). METHOD: 98 adult PE were prospectively screened for risk of OSA by Berlin questionnaire. Data was also collected about excessive daytime sleepiness, depression, anxiety, clinical and socio-demographic characteristics. RESULTS: The PE main characteristics: 59 men/39-women, mean age=39.97, SD=12.3, range 18-66. The prevalence of the risk of OSA was 55.1% (CI 95%, 0.45-0.65). The high risk for OSA was related with body mass index (BMI) (p=0.000), neck circumference (NC) (p=0.000), arterial hypertension (AH) (p=0.000), and anxiety (p=0.006), without relationship with number of seizures, number of antiepileptic drugs, age or depression. The NC was statistically significant regarding risk of OSA, mainly in men. CONCLUSION: We found a high risk of OSA in this sample. The main implicated measures were the large NC, high BMI and anxiety. The anthropometric variables were more relevant than those related to epilepsy itself and similar to those of the general population. PMID- 22297882 TI - Patients with sudden onset headache not meeting the criteria of the International Headache Society for new daily persistent headache. How to classify them? AB - We conducted a retrospective analysis of the records of 1348 patients regularly treated at the headache clinic of Department of Neurology of Santa Casa de Sao Paulo, Brazil. Sixty-two patients reported history of daily and persistent headache. From the 62 patients selected, only 21 (group 1) could be diagnosed with new daily-persistent headache (NDPH) according to the International Headache Society (HIS) 2004 criteria. The 41 remaining patients (group 2) could not be diagnosed with NDPH according to IHS-2004 once they presented two or more migraine attack-related symptoms, such as: nausea, photophobia, phonophobia and vomiting, in different combinations. It was not possible to classify them in groups 1 to 4 of primary headaches either. How to classify them? We suggest that the criteria are revised. And one way we can classify them, would be the subdivision: NDPH with migraine features and without migraine features that would allow the inclusion of all individuals present who has a daily and persistent headache from the beginning. PMID- 22297883 TI - Thermal record of the test tubes method used for small fibers assessment. AB - In Brazil, the test that uses test tubes filled with cold water (25oC) and tubes filled with water heated to a temperature of 45oC is recommended by the Ministry of Health as a way of evaluate thermal sensitivity on the injured skin of leprosy patients. The purpose of this work was to quantify the thermal stimulation applied to the skin, as well as the temperature variation of the heated water and of the tube's outer surface during stimulation sessions. The experiment had the participation of 14 healthy volunteers (31.2 +/- 11.4 years-old), ten of which were male (33.1 +/- 13.5 years-old) and four were female (26.5 +/- 4.7 years old). Three consecutive stimulation sessions were carried out, each of them with four stimuli. The maximum skin temperature at the end of the stimuli was measured at 35.8 +/- 0.6oC. Such temperature values may be useful in the assessment of the loss of small fibers, which are responsible for the sensation of warmth. PMID- 22297884 TI - Behavioral investigation of mice with experimental autoimmune encephalomyelitis. AB - Multiple sclerosis is a neuroinflammatory disease that results in serious neurological disability. Besides physical impairment, behavioral symptoms are also common in patients with multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is considered to be a model of multiple sclerosis and mimics the main features of the disease, such as demyelination and motor impairment. In this work, we aimed to study behavioral parameters in animals with EAE using the MOG(35-55) model in C57BL/6 mice. We analyzed memory and anxiety in animals using the elevated plus maze, the step down inhibitory avoidance task and the memory recognition test. No differences in any tests were found when comparing controls and animals induced with EAE. Therefore, we conclude that behavioral changes in animals with EAE induced with MOG(35-55) are probably subtle or absent. PMID- 22297885 TI - Validation of a Brazilian quantitative sensory testing (QST) device for the diagnosis of small fiber neuropathies. AB - Quantitative sensory testing (QST) is defined as the determination of thresholds for sensory perception under controlled stimulus. Our aim was to validate a new QST device for Brazilian sample. In 20 healthy adults, thermoalgesic thresholds were assessed using a QST prototype (Heat Pain Stimulator-1.1.10; Brazil). A 30 * 30 mm(2) thermode with a 1 degrees C/s stimulus change rate were applied. Thresholds of three consecutive stimuli were averaged in two different sessions separated by at least two weeks. Additionally long thermal heat pain stimulus was performed. To evaluate the consistency of our method we also analyzed 11 patients with small fiber neuropathy. Results showed good reproducibility of thermal perception thresholds in normal individuals and plausible abnormal thresholds in patients. We conclude that our QST device is reliable when analyzing the nociceptive pathway in controls and patients. PMID- 22297886 TI - Use of intraoperative MRI for resection of gliomas. AB - Literature has shown that extent of tumor resection has an impact on quality of life and survival of patients with gliomas. Intraoperative MRI has been used to increase resection while preserving procedure's safety. METHOD: The first five patients with gliomas operated on at the University of Sao Paulo using intraoperative MRI are reported. All but one patient had Karnofsky Performance Status of 100% before surgery. Presentation symptoms were progressive headache, seizures, behavior disturbance, one instance of hemianopsia, and another of hemiparesis. RESULTS: Gross total removal was achieved in two patients. Surgical resection was limited by tumor invasion of critical areas like the internal capsule or the mesencephalon in the remaining patients. CONCLUSION: Intra operative MRI is an important tool that helps surgeons to remove glial tumors, however, knowledge of physiology and functional anatomy is still fundamental to avoid morbidity. PMID- 22297887 TI - Rethinking the neurological examination I: static balance assessment. AB - The authors advocate a modernization of the neurologic exam with regard to the evaluation of static equilibrium through the application of some easily performed and interpreted bedside maneuvers like the Clinical Test of Sensory Integration and Balance - modified and the Functional Reach Test. The authors also believe that these and other assessments, such as that of the risk of falling for elderly patients, should be incorporated into the routine neurological examination. PMID- 22297888 TI - Rethinking the neurological examination II: dynamic balance assessment. AB - The authors propose that the neurological exam needs reevaluation with respect to the dynamic balance test (walking). Validated tests such as: preferred and maximum gait speed, dynamic gait index, five-times-sit-to-stand test, timed up & go cognitive and manual, should be part of the neurological examination routine. In the neurological exam of older patients, these same bedside tests bring the plus of evaluation the risk of occasional falling. PMID- 22297889 TI - Genotypical diversity of HIV clades and central nervous system impairment. AB - The central nervous system (CNS) and the immune system are considered major target organs for HIV infection. The neurological manifestations directly related to HIV are acute viral meningitis, chronic meningitis, HIV associated dementia, vacuolar myelopathy and involvement of the peripheral nervous system. Changes in diagnosis and clinical management have changed the aspect of HIV infection so that it is no longer a fatal disease, and has become a chronic disease requiring sustained medical management. After HAART the incidence of most opportunistic infections, including those affecting the CNS, has dropped markedly. Some studies suggest that neurological involvement of infected patient occur with different frequency, depending on HIV subtype involved in the infection. Subtype C may have reduced neuroinvasive capacity, possibly due to its different primary conformation of HIV transactivating regulatory protein (Tat), involved in monocyte chemotaxis. This review focus on physiopathologic aspects of HIV infection in CNS and its correlation with HIV clades. PMID- 22297890 TI - Meningeal carcinomatosis in solid tumors. AB - The involvement of the leptomeninges by metastatic tumors can be observed in solid tumors, in which case it is termed meningeal carcinomatosis (MC), and in lymphoproliferative malignant disease. It is more common in breast and lung cancer, as well as melanoma, with adenocarcinoma being the most frequent histological type. MC is usually a late event, with disseminated and progressive disease already present and, it is characterized by multifocal neurological signs and symptoms. Diagnosis is based on the evaluation of clinical presentation, cerebrospinal fluid and neuroimaging studies. The better systemic disease control is observed with new therapeutic agents, and the development of neuroimaging methods is responsible for the increasing incidence of such metastatic evolution. Intrathecal chemotherapy is generally the treatment of choice, although frequently palliative. Prognosis is guarded, although a higher performance status may indicate a subgroup of patients with a more favorable outcome. PMID- 22297891 TI - Selective therapeutic hypothermia: a review of invasive and noninvasive techniques. AB - OBJECTIVE: Therapeutic hypothermia is a promising treatment to prevent secondary neurologic injury. Clinical utility is limited by systemic complications of global hypothermia. Selective brain cooling remains a largely uninvestigated application. We review techniques of inducing selective brain cooling. METHOD: Literature review. RESULTS: Strategies of inducing selective brain cooling were divided between non-invasive and invasive techniques. Non-invasive techniques were surface cooling and cooling via the upper airway. Invasive cooling methods include transvascular and compartmental (epidural, subdural, subarachnoid and intraventricular) cooling methods to remove heat from the brain. CONCLUSION: Selective brain cooling may offer the best strategy for achieving hypothermic neuroprotection. Non-invasive strategies have proven disappointing in human trials. There is a paucity of human experiments using invasive methods of selective brain cooling. Further application of invasive cooling strategies is needed. PMID- 22297892 TI - Pineal region hemangioblastoma in a patient with Von Hippel-Lindau disease. PMID- 22297893 TI - Association between a ruptured distal anterior inferior cerebral artery aneurysm and arteriovenous malformation fed by the same artery. PMID- 22297894 TI - Subacute cognitive impairment, hyponatremia and mesial temporal lobe lesions: a typical presentation of voltage-gated potassium channel (VGKC) antibody associated limbic encephalitis. PMID- 22297895 TI - Acute intermittent porphyria after gastroplasty. PMID- 22297896 TI - Cerebellar ataxia associated to anti-glutamic acid decarboxylase autoantibody (anti-GAD): partial improvement with intravenous immunoglobulin therapy. PMID- 22297897 TI - Vasculitic neuropathy presenting as Churg-Strauss paraneoplastic syndrome: a rare association. PMID- 22297898 TI - Endometriosis of the sciatic nerve. PMID- 22297899 TI - Supratentorial primitive neuroectodermal tumor (PNET): an uncommon location. PMID- 22297900 TI - Treatment of West syndrome with vigabatrin: reversible MRI signal changes. PMID- 22297901 TI - Polyploid origin, genetic diversity and population structure in the tetraploid sea lavender Limonium narbonense Miller (Plumbaginaceae) from eastern Spain. AB - Limonium narbonense Miller is a fertile tetraploid species with a sporophytic self-incompatibility system. This sea lavender is found in coastal salt marshes which have been under intense human pressure during the past decades resulting in significant habitat fragmentation. Eleven microsatellite loci specifically designed for this species were amplified in 135 individuals from five populations. These markers were used to investigate the polyploid nature, the levels of genetic diversity and population structure in this species. L. narbonense showed high levels of genetic diversity (A = 7.82, P = 100% H (T) = 0.446), consistent with its likely autotetraploid origin revealed in this study and obligate outcrossing breeding system. Inbreeding (F (IS)) values were low in the three southern populations (mean F (IS) = 0.062), and higher in the northern populations (mean F (IS) = 0.184). Bayesian analysis of population structure revealed that populations could be grouped into two genetic clusters, one including three southern populations and the other the two northernmost ones. Individuals from the two northernmost populations showed higher admixture of the two genetic clusters than individuals from the three southern ones. A thorough analysis of microsatellite electrophoretic patterns suggests an autotetraploid origin for L. narbonense. The genetic structure revealed in this study is attributed to a recent migration from the southern area. This result suggests a net gene flow from the south to the north, likely facilitated by migratory movements of birds visiting the temporary flooded ponds occupied by L. narbonense. PMID- 22297902 TI - Comparison of a colorimetric and a high-performance liquid chromatography method for the determination of fructan in pasture grasses for horses. AB - BACKGROUND: Pasture (fresh or conserved as hay/haylage) forms the basis of most equid diets and contains varying amounts (0 to >= 200 g kg-1 dry matter (DM) or more) of fructans. Over-consumption of fructan is associated with the onset of laminitis in equids, an agonizing condition that may necessitate euthanasia. To enable appropriate dietary management of animals susceptible to laminitis, it is essential that fructans can be properly quantified in fresh and conserved pasture. For research purposes, fructans are frequently quantified by high performance liquid chromatography (HPLC), but these methods are costly for routine screening. However, an inexpensive colorimetric method for measuring fructans in human foods is commercially available. The aim here was to determine the suitability of the commercially available colorimetric method for determining the fructan content of pasture grasses for horses. RESULTS: Pasture grasses (Phleum pretense, Festuca rubra, Dactylis glomerata, Lolium perenne) managed for grazing (sampled from April to November) and a further set managed for conservation (sampled in July) were analysed for fructan content by HPLC and the colorimetric technique. HPLC values ranged from 83 to 299 g fructan kg-1 DM (mean 154); corresponding colorimetric values were 5-238 g fructan kg-1 DM (mean 82). Discrepancies in values between the two methods varied with time of sampling and plant species. Comparison of selected samples before and after incubation with the fructan hydrolases used in the colorimetric method revealed incomplete fructan hydrolysis from the pasture grasses, resulting in underestimates of their fructan content. CONCLUSION: The colorimetric technique was not a reliable substitute for HPLC to quantify the fructan content of pasture grasses. PMID- 22297903 TI - Comprehensive chemical profiling of guizhi fuling capsule by the combined use of gas chromatography-mass spectrometry with a deconvolution software and rapid resolution liquid chromatography quadrupole time-of-flight tandem mass spectrometry. AB - Herbal formulations are complex natural mixtures. Researchers usually tend to focus more on analysis of nonvolatile components but pay less attention to volatile compounds. In this study, an analytical strategy combining two approaches was established for comprehensive analysis of herbal formulations. Guizhi Fuling capsule (GFC), a drug approved by the FDA to enter phase II clinical trial for treatment of primary dysmenorrhea, was taken as a case for analysis. Gas chromatography-mass spectrometry (GC-MS) with automated mass spectral deconvolution and identification system (AMDIS) led to rapid identification of 48 volatile components including four acetophenones, three fatty acid esters, 13 phenylpropanoids and 19 sesquiterpenes. Most of them were found from Guizhi. The volatile oils of Guizhi have been proved to exhibit many pharmacological activities. This is helpful in understanding the pharmacological mechanism of GFC. Furthermore, AMDIS turned out to be efficient and reliable for analysis of complex herbal formulations. Rapid-resolution liquid chromatography (RRLC) coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI-Q-TOF MS/MS) allowed the identification of 70 nonvolatile components including six acetophenones, 12 galloyl glucoses, 31 monoterpene glycosides, three phenols and 12 triterpene acids. Fragmentation behaviors of assigned components, especially triterpene acids, which are hard to identify by low-resolution MS, were first investigated by TOF MS/MS. Characteristic ions and typical loss of assigned triterpene acids were summarized. Combinatorial use of GC-MS-AMDIS and RRLC-ESI-Q-TOF MS/MS could be of great help in global qualitative analysis of GFC, as well as other herbal products. PMID- 22297904 TI - Knowledge and attitude regarding recovery among mental health practitioners in Sweden. AB - The aim was to investigate the knowledge and the attitude regarding recovery among practitioners working in the Swedish mental health system, Personligt Ombud (PO), Supported Housing Team (SHT) and Psychiatric Out Patient Service (POPS), to determine whether and how knowledge and attitude regarding recovery differ between the three services. A web-based questionnaire based on the Recovery Knowledge Inventory was sent to the participants. Participant selection ensured that different parts of Sweden were represented. A multiple linear regression was used to examine the result under control of Sex, Age, Educational Level, Further Education, Relevant Work Experience and Training in Recovery. The result of the regression showed that POs had higher scores than both SHT and POPS on the subscales, even under control of other variables. The SHT differed significantly from POs on two of the subscales and POPS differed significantly from POs on all subscales. Personnel with university education, more work experience or specific training in recovery also had a higher mean score. Swedish practitioners need to learn more about certain aspects of the recovery process. The differences between the services may possibly be due to the services' organization, assignment and role. Other important aspects were the level of education and having specific training in recovery; the combination of these elements could facilitate the development of a recovery-oriented mental health system. PMID- 22297905 TI - Use of fluorine-doped silicon oxide for temperature compensation of radio frequency surface acoustic wave devices. AB - This paper investigates acoustic properties, including the temperature coefficient of elasticity (TCE), of fluorine-doped silicon oxide (SiOF) films and proposes the application of the films to the temperature compensation of RF SAW devices. From Fourier transform infrared spectroscopy (FT-IR), SiOF films were expected to possess good TCE properties. We fabricated a series of SAW devices using the SiOF-overlay/Cu-grating/LiNbO(3)-substrate structure, and evaluated their performance. The experiments showed that the temperature coefficient of frequency (TCF) increases with the fluorine content r, as we expected from the FT IR measurement. This means that the Si-O-Si atomic structure measurable by the FT IR governs the TCE behavior of SiO(2)-based films even when the dopant is added. In comparison with pure SiO(2) with the film thickness h of 0.3 wavelengths (lambda), TCF was improved by 7.7 ppm/ degrees C without deterioration of the effective electromechanical coupling factor K2 when r = 3.8 atomic % and h = 0.28lambda. Fluorine inclusion did not obviously influence the resonators' Q factors when r < 8.8 atomic %. PMID- 22297906 TI - Screening for disease. PMID- 22297907 TI - Screening for thyroid disease and iodine deficiency. AB - The high global prevalence of iodine deficiency and autoimmune thyroid disorders and the mental and physical consequences of these disorders creates a huge human and economic burden that can be prevented, in large part, by early detection and appropriate preventative or therapeutic measures. The availability of sophisticated, sensitive and accurate laboratory testing procedures provides an efficient and effective platform for the application of screening for these disorders. Measurement of urine iodine concentration (UIC) in school children or pregnant women is the recommended indicator for screening populations for iodine deficiency. The severity of the iodine deficiency is classified according to the UIC. Measurement of serum thyrotropin (TSH) as an indicator for population iodine deficiency is used only in neonates and is supplementary to UIC screening. Other indicators such as goitre rates, thyroid function and serum thyroglobulin levels are useful adjunctive but not frontline process indicators. The human and economic benefits of screening for congenital hypothyroidism by measurement of heel-prick TSH have been well documented and justify its universal application. Using this measurement for monitoring population iodine intake is recommended by the World Health Organization but further validation is required before it can be universally recommended. Subclinical thyroid dysfunction is readily detected by current highly sensitive serum TSH assays and its prevalence appears to increase with age, varies with iodine intake and ethnicity and may occur in up to 20% of older age people. Subclinical hyperthyroidism is the less common disorder and screening cannot be justified because of its low prevalence and minimal or insignificant clinical effects. The argument for screening for subclinical hypothyroidism in middle-aged and older women is stronger but lacks evidence of benefit from randomised controlled trials or cost benefit analyses of therapeutic intervention, so it cannot currently be recommended. The publication of recent Clinical Practice Guidelines for management of thyroid disease in pregnancy from the American Endocrine Society and American Thyroid Association provide persuasive arguments for early detection and treatment of overt and subclinical hypothyroidism to prevent obstetric complications and potential neurocognitive disorders in the offspring. Given the indisputable benefits of therapy, the sooner thyroid dysfunction is detected, before or as early as possible in gestation, the more likely there will be a better outcome. Because of the limitations of targeted case detection in women at risk of subclinical hypothyroidism, there has been a gradual shift in opinion to universal TSH screening of all women as soon as practicable in pregnancy. While a positive association exists between the presence of anti-thyroid antibodies and increased pregnancy loss, universal screening of all pregnant women for underlying autoimmune thyroid disease is difficult to justify until there is evidence of beneficial outcomes from randomised controlled trials. Vigorous and liberal targeted case detection remains the recommended strategy to address this problem. PMID- 22297908 TI - Gold nanostar synthesis with a silver seed mediated growth method. AB - The physical, chemical and optical properties of nano-scale colloids depend on their material composition, size and shape. There is a great interest in using nano-colloids for photo-thermal ablation, drug delivery and many other biomedical applications. Gold is particularly used because of its low toxicity. A property of metal nano-colloids is that they can have a strong surface plasmon resonance. The peak of the surface plasmon resonance mode depends on the structure and composition of the metal nano-colloids. Since the surface plasmon resonance mode is stimulated with light there is a need to have the peak absorbance in the near infrared where biological tissue transmissivity is maximal. We present a method to synthesize star shaped colloidal gold, also known as star shaped nanoparticles or nanostars. This method is based on a solution containing silver seeds that are used as the nucleating agent for anisotropic growth of gold colloids. Scanning electron microscopy (SEM) analysis of the resulting gold colloid showed that 70 % of the nanostructures were nanostars. The other 30 % of the particles were amorphous clusters of decahedra and rhomboids. The absorbance peak of the nanostars was detected to be in the near infrared (840 nm). Thus, our method produces gold nanostars suitable for biomedical applications, particularly for photo-thermal ablation. PMID- 22297909 TI - Manipulation of triose phosphate/phosphate translocator and cytosolic fructose 1,6-bisphosphatase, the key components in photosynthetic sucrose synthesis, enhances the source capacity of transgenic Arabidopsis plants. AB - Photoassimilated carbons are converted to sucrose in green plant leaves and distributed to non-phototropic tissues to provide carbon and energy. In photosynthetic sucrose biosynthesis, the chloroplast envelope triose phosphate/phosphate translocator (TPT) and cytosolic fructose-1,6-bisphosphatase (cFBPase) are key components in photosynthetic sucrose biosynthesis. The simultaneous overexpression of TPT and cFBPase was utilized to increase the source capacity of Arabidopsis. The TPT and cFBPase overexpression lines exhibited enhanced growth with larger rosette sizes and increased fresh weights compared with wild-type (WT) plants. The simultaneous overexpression of TPT and cFBPase resulted in enhanced photosynthetic CO(2) assimilation rates in moderate and elevated light conditions. During the phototropic period, the soluble sugar (sucrose, glucose, and fructose) levels in the leaves of these transgenic lines were also higher than those of the WT plants. These results suggest that the simultaneous overexpression of TPT and cFBPase enhances source capacity and consequently leads to growth enhancement in transgenic plants. PMID- 22297911 TI - The FX iron-sulfur cluster serves as the terminal bound electron acceptor in heliobacterial reaction centers. AB - Phototrophs of the family Heliobacteriaceae contain the simplest known Type I reaction center (RC), consisting of a homodimeric (PshA)(2) core devoid of bound cytochromes and antenna proteins. Unlike plant and cyanobacterial Photosystem I in which the F(A)/F(B) protein, PsaC, is tightly bound to P(700)-F(X) cores, the RCs of Heliobacterium modesticaldum contain two F(A)/F(B) proteins, PshBI and PshBII, which are loosely bound to P(800)-F(X) cores. These two 2[4Fe-4S] ferredoxins have been proposed to function as mobile redox proteins, reducing downstream metabolic partners much in the same manner as does [2Fe-2S] ferredoxin or flavodoxin (Fld) in PS I. Using P(800)-F(X) cores devoid of PshBI and PshBII, we show that iron-sulfur cluster F(X) directly reduces Fld without the involvement of F(A) or F(B) (Fld is used as a proxy for soluble redox proteins even though a gene encoding Fld is not identified in the H. modesticaldum genome). The reduction of Fld is suppressed by the addition of PshBI or PshBII, an effect explained by competition for the electron on F(X). In contrast, P(700) F(X) cores require the presence of the PsaC, and hence, the F(A)/F(B) clusters for Fld (or ferredoxin) reduction. Thus, in H. modesticaldum, the interpolypeptide F(X) cluster serves as the terminal bound electron acceptor. This finding implies that the homodimeric (PshA)(2) cores should be capable of donating electrons to a wide variety of yet-to-be characterized soluble redox partners. PMID- 22297912 TI - Antileishmanial activity of cryptolepine analogues and apoptotic effects of 2,7 dibromocryptolepine against Leishmania donovani promastigotes. AB - Cryptolepine (5-methyl-10H-indolo [3, 2-b] quinoline), an indoloquinoline alkaloid (1) isolated from a medicinal plant traditionally used in Western Africa for treatment of malaria, has been shown to possess broad spectrum biological activity in addition to its antiplasmodial effect. Here, the antileishmanial properties of 11 synthetic derivatives of cryptolepine against Leishmania donovani parasites have been evaluated for the first time. 2,7 Dibromocryptolepine (8; IC50 0.5 +/- 0.1 MUM) was found to be the most active analogue against the promastigote form of a classical L. donovani strain (AG83) in comparison to the natural alkaloid, cryptolepine (1; IC50 1.6 +/- 0.1 MUM). Further, 8 was found to substantially inhibit the intracellular amastigote forms of two clinical isolates, one of them being an SbV-resistant strain of L. donovani. Moreover, the toxicity of 8 against normal mouse peritoneal macrophage cells was markedly lower than that of 1 (IC50 values: 9.0 +/- 1.2 and 1.1 +/- 0.3 MUM, respectively), indicating 8 to be a prospective "lead" towards novel antileishmanial therapy. This was supported by studies on the mechanism of cytotoxicity induced by 8 in L. donovani promastigotes (AG83), which revealed the cytoplasmic and nuclear features of metazoan apoptosis. Light microscopic observation demonstrated a gradual decline in the motility, cell volume, and survival of the treated parasites with increasing incubation time. Flow cytometric analysis of phosphatidylserine externalization and distribution of cells in different phases of cell cycle confirmed the presence of a substantial percentage of cells in early apoptotic stage. Disruption of mitochondrial membrane integrity in terms of depolarization of membrane potential, and finally degradation of chromosomal DNA into oligonucleosomal fragments - the hallmark event of apoptosis - characterized the mode of cell death in L. donovani promastigotes. PMID- 22297913 TI - [An unusual case of bridge vein thrombosis with subsequent dural arteriovenous fistula as a sequela of sinus rectus thrombosis - a rare association]. PMID- 22297914 TI - [Evaluation of radiation dose in 64-row whole-body CT of multiple injured patients compared to 4-row CT]. AB - PURPOSE: To evaluate radiation exposure in whole-body CT (WBCT) of multiple injured patients comparing 4-row multidetector computed tomography (MDCT) to 64 row MDCT. MATERIALS AND METHODS: 200 WBCT studies were retrospectively evaluated: 92 4-row MDCT scans and 108 64-row MDCT scans. Each CT protocol was optimized for the particular CT system. The scan length, CT dose index (CTDI), and dose length product (DLP) were recorded and analyzed for radiation exposure. The mean effective dose was estimated based on conversion factors. Student's t-test was used for statistical analysis. RESULTS: The mean CTDIvol values (mGy) of the thorax and abdomen were significantly reduced with 64-row MDCT (10.2+/-2.5 vs. 11.4+/-1.4, p<0.001; 14.2+/-3.7 vs. 16.1+/-1.7, p<0.001). The DLP values (mGy*cm) of the head and thorax were significantly increased with 64-row MDCT (1305.9+/ 201.1 vs. 849.8+/-90.9, p<0,001; 504.4+/-134.4 vs. 471.5+/-74.1, p=0.030). The scan lengths (mm) were significantly increased with 64-row MDCT: head 223.6+/ 35.8 vs. 155.5+/-12.3 (p<0.001), thorax 427.4+/-44.5 vs. 388.3+/-57.5 (p<0.001), abdomen 520.3+/-50.2 vs. 490.8+/-51.6 (p<0.001). The estimated mean effective doses (mSv) were 22.4+/-2.6 (4-row MDCT) and 24.1+/-4.6 (64-row MDCT; p=0.001), resulting in a percentage increase of 8%. CONCLUSION: The radiation dose per slice of the thorax and abdomen can be significantly decreased by using 64-row MDCT. Due to the technical advances of modern 64-row MDCT systems, the scan field can be adapted to the clinical demands and, if necessary, enlarged without time loss. As a result, the estimated mean effective dose might be increased in WBCT. PMID- 22297915 TI - [Percutaneous CT-guided high-dose brachytherapy (CT-HDRBT) ablation of primary and metastatic lung tumors in nonsurgical candidates]. AB - PURPOSE: To evaluate the safety and efficacy of CT-guided high-dose brachytherapy (CT-HDRBT) ablation of primary and metastatic lung tumors. MATERIALS AND METHODS: Between November 2007 and May 2010, all consecutive patients with primary or metastatic lung tumors, unsuitable for surgery, were treated with CT-HDRBT. Imaging follow-up after treatment was performed with contrast-enhanced CT at 6 weeks, 3 months and every 6 months after the procedure. The endpoints of the study were local tumor control and time to progression. The Kaplan-Meier method was used to estimate survival functions and local tumor progression rates. RESULTS: 34 procedures were carried out on 33 lesions in 22 patients. The mean diameter of the tumors was 33.3 mm (SD = 20.4). The first contrast-enhanced CT showed that complete ablation was achieved in all lesions. The mean minimal tumor enclosing dose was 18.9 Gy (SD = 2). Three patients developed a pneumothorax after the procedure. The mean follow-up time was 13.7 (3 - 29) months. 2 of 32 lesions (6.25 %) developed a local tumor progression. 8 patients (36.3 %) developed a distant tumor progression. After 17.7 months, 13 patients were alive and 9 patients had died. CONCLUSION: CT-HDRBT ablation is a safe and attractive treatment option for patients with lung malignancies and allows targeted destruction of tumor tissue with simultaneous preservation of important lung structures. Furthermore, CT-HDRBT is independent of the size of the lesion and its location within the lung parenchyma. PMID- 22297916 TI - [Mechanical thrombectomy for acute ischemic stroke]. AB - The therapy of acute ischemic stroke aims at fast recanalization of the occluded brain vessel. In contrast to intravenous thrombolysis (IVT), endovascular approaches yield higher recanalization rates especially in large vessel occlusions. Mechanical thrombectomy with the Merci Retriever received FDA approval in 2004 as an adjunct to IVT or in the case of failed recanalization after IVT. The time window for treatment is 8 h from stroke onset. However, the recanalization rate was 55 %, still leaving space for further improvement. In addition to the Merci Retriever, the Penumbra System received FDA approval in 2008. The newest endovascular approach comprising retrievable intracranial stents results in an increased recanalization rate exceeding 90 % and has markedly reduced the time to recanalization. On the other hand, the complication rate has not increased yet. These promising results suggest a combined therapy for acute ischemic stroke. In a first step IVT can be started independently of the size of the treating hospital and in a next step the patient is transferred to a neuroradiological center. If vessel occlusion persists, additional endovascular recanalization is performed (bridging concept). Patients who don't qualify for IVT are candidates for mechanical thrombectomy up to 8 h after stroke onset. PMID- 22297917 TI - Mental health and asthma in China: the Guangzhou Biobank Cohort Study. AB - BACKGROUND: There is consistent evidence of the co-occurrence of poor mental health and asthma in Western populations. Since the experience and expression of mental health is partly culturally determined, it is of interest to examine if similar associations are found in other cultural settings. In that regard, very little is known about the association between mental health and asthma in Asian countries, such as China. PURPOSE: The aim of this study was to investigate the relationship between mental health and asthma in a large sample from China. METHOD: We used data from the Guangzhou Biobank Cohort Study phase 3 (n = 9,280). Participants reported physician-diagnosed asthma. Mental health measures included the 15-item Chinese version of the Geriatric Depression Scale (GDS-C) and the SF 12 Mental Component Summary (MCS) score. We compared the prevalence of asthma by GDS-C and MCS scores by estimating prevalence ratios (PRs) and their corresponding 95% confidence intervals (95% CI), using Poisson regression. RESULTS: Compared to those without depression, the prevalence of asthma was higher in those with moderate or severe depression levels (PR = 2.63, 95% CI = 1.58-4.40 and PR = 4.43, 95% CI = 1.62-12.09, p for trend <=0.0001). The prevalence of asthma increased by 46% with every 1 standard deviation increase of the GDS-C score (PR = 1.46, 95% CI = 1.24-1.73). The MCS score was not associated with asthma. CONCLUSION: Depressive symptoms were associated with asthma prevalence in a Chinese population. Further research into the mechanism and potential directions of causality is warranted. PMID- 22297918 TI - [Measurement of physical activity in older adults. Correlation between the PRISCUS-PAQ and accelerometry]. AB - BACKGROUND: The German questionnaire PRISCUS-PAQ was developed to measure actual physical activity of older adults in a telephone interview. PRISCUS-PAQ consists of ten main questions to assess the time spend in domestic activities (e.g., housework, gardening), sporting activities (e.g., riding a bicycle), and inactivity (e.g., sedentary activity, sleeping during the day) during the prior week. By assessing the number of days for each activity and the mean duration of performing this activity, a total score can be calculated. The total score corresponds to the energy consumption for 1 week. The aim of this study is to estimate the correlation of the PRISCUS-PAQ total score and accelerometry as an objective measurement method for the assessment of physical activity. MATERIAL AND METHODS: A total of 114 participants (58% women) with a mean age of 76 years participated in the study. PRISCUS-PAQ was initially analyzed descriptively. To assess the validity of PRISCUS-PAQ, the correlation (correlation coefficient of Spearman) was calculated between the total score of the questionnaire PRISCUS-PAQ and the 95% trimmed sum of an accelerometer with a measurement period of 1 week. RESULTS: The correlation coefficient for the association of the PRISCUS-PAQ total score and the 95% trimmed sum of the acceleration values was r = 0.28 (95% confidence interval 0.10-0.44). Activities of daily life like cleaning and other domestic activities highly contributed to the weekly energy consumption of the participants. CONCLUSION: The association between the PRISCUS-PAQ questionnaire and accelerometry measured physical activity is comparable to other validated and established international questionnaires. The PRISCUS-PAQ is the first German questionnaire that allows the measurement of physical activity of older adults in a telephone interview. PMID- 22297919 TI - [Candida infections in the elderly]. AB - Candida infections of the skin, mucous membranes as well as of internal organs may be more frequent and more serious in the elderly. There are several biological reasons for this, for example, alterations in the immune system. Whereas Candida albicans remains the major pathogen, there has been a relative increase of Candida glabrata infections. This species is associated with higher mortality. Furthermore, C. glabrata is in general less susceptible to fluconazole, so that this drug does not represent the agent of first choice for the treatment of yeast infections. The choice of the antimycotic agent must take into consideration their inherent side effects and interaction profiles; echinocandins play a particular role in the treatment of yeast infections in the elderly. These drugs have low toxicities, low potential for interactions with co medications, as well as broad and good activities against yeasts. PMID- 22297921 TI - Theoretical studies on the Mo-catalyzed asymmetric intramolecular Pauson-Khand type [2+2+1] cycloadditions of 3-allyloxy-1-propynylphosphonates. AB - Density functional theory (DFT) was used to investigate the Mo-catalyzed intramolecular Pauson-Khand reaction of 3-allyloxy-1-propynylphosphonates. All intermediates and transition states were optimized completely at the B3LYP/6-31 G(d,p) level [LANL2DZ(f) for Mo]. In the Mo-catalyzed intramolecular Pauson-Khand reaction, the C-C oxidative cyclization reaction was the chirality-determining step, and the reductive elimination reaction was the rate-determining step. The carbonyl insertion reaction into the Mo-C(sp(3)) bondwas easier than into the Mo C=C bond. And the dominant product predicted theoretically was of (S)-chirality, which agreed with experimental data. This reaction was solventd ependent, and toluene was the best among the three solvents toluene, CH3CN, and THF. PMID- 22297922 TI - Fabrication of coaxial TiO2/Sb2S3 nanowire hybrids for efficient nanostructured organic-inorganic thin film photovoltaics. AB - We report on low-cost, all solution fabrication of efficient air-stable nanostructured thin film photovoltaics comprised of n-type Sb(2)S(3) chemically deposited onto TiO(2) nanowire array films, forming coaxial Sb(2)S(3)/TiO(2) nanowire hybrids vertically oriented from the SnO(2):F coated glass substrate, which are then intercalated with poly(3-hexylthiophene) (P3HT) for hole transport and enhanced light absorption. PMID- 22297923 TI - Sinus imaging for diagnosis of chronic rhinosinusitis in children. AB - Chronic rhinosinusitis (CRS) is a relatively common disease in children but is often overlooked because at times the clinical symptoms are subtle and nonspecific. This makes imaging very important in the diagnosis. Among the different techniques, plain radiography has limited utility,whereas CT scan and MRI have a major role in evaluating the modifications caused by the disease. In particular, a CT scan provides higher resolution of bone and soft tissue and removes the overlapping structures that are present in conventional radiography. CT is recommended in isolated sphenoid sinusitis, is essential in diagnosing fungal sinusitis, and is the technique of choice when orbital complications are suspected. MRI allows investigation of not only the morphology of structures, but their intrinsic biophysical and biochemical properties, such as water content, cellular density, lipid or blood product deposits, and fibrosis. MRI allows better soft tissue differentiation and high spatial resolution images depicting fine details. When indicated, MRI with contrast gadolinium-based agents may better characterize the local disease extension or its diffusion beyond paranasal and nasal cavities and has excellent contrast resolution. A combination of CT and MRI is useful in cases of diagnostic difficulties,especially when complications are involved. PMID- 22297924 TI - Management of Smell Dysfunction. AB - Olfaction is an essential chemosensory system in the living world. Although less appreciated in humans, smell impairment significantly affects many aspects of quality of life. Smell disorders may be caused by an impaired nasal airway or by lesions in the olfactory system, leading to reduced or distorted smell perception. The most common causes of smell disorders are aging, upper respiratory tract infection, sinonasal disease, and head trauma. Recovery is rarely complete. Counseling is important in progressive or severe smell loss. In patients with distorted smell perception, antidepressant medication is sometimes necessary. Best response to treatment is achieved for nasal obstruction and sinonasal inflammatory disease. Treatment of olfactory impairment caused by sinonasal disease includes medication with topical and systemic steroids, or surgery for refractory cases. Although there are reports that surgical resection of olfactory neurons may lead to reinnervation and recovery of smell, adequate treatment of the smell loss remains an unmet need. PMID- 22297925 TI - Changes in hospital efficiency after privatization. AB - We investigated the effects of privatization on hospital efficiency in Germany. To do so, we obtained boot-strapped data envelopment analysis (DEA) efficiency scores in the first stage of our analysis and subsequently employed a difference in-difference matching approach within a panel regression framework. Our findings show that conversions from public to private for-profit status were associated with an increase in efficiency of between 2.9 and 4.9%. We defined four alternative post-privatization periods and found that the increase in efficiency after a conversion to private for-profit status appeared to be permanent. We also observed an increase in efficiency for the first three years after hospitals were converted to private non-profit status, but our estimations suggest that this effect was rather transitory. Our findings also show that the efficiency gains after a conversion to private for-profit status were achieved through substantial decreases in staffing ratios in all analyzed staff categories with the exception of physicians and administrative staff. It was also striking that the efficiency gains of hospitals converted to for-profit status were significantly lower in the diagnosis-related groups (DRG) era than in the pre-DRG era. Altogether, our results suggest that converting hospitals to private for-profit status may be an effective way to ensure the scarce resources in the hospital sector are used more efficiently. PMID- 22297927 TI - Luminescence properties of K1/2Bi1/2TiO3:Pr3+ and Na1/2Bi1/2TiO3:Pr3+. AB - The luminescence properties of K(1/2)Bi(1/2)TiO(3):Pr(3+) and Na(1/2)Bi(1/2)TiO(3):Pr(3+) powders are investigated in the temperature range 10 600 K. The experimental data are interpreted on the basis of metal-to-metal charge transfer processes and by considering Bi(3+)-to-Pr(3+) sensitization effects. PMID- 22297926 TI - Ancillary information improves kriging on soil organic carbon data for a typical karst peak cluster depression landscape. AB - BACKGROUND: Soil carbon management at landscape scale requires reliable information on the spatial distribution of soil organic carbon (SOC). However, how to improve the accuracy of spatial prediction is not well addressed in the karst region of southwestern China. This study evaluates the performance of univariate kriging (ordinary kriging (OK)) and hybrid kriging (co-kriging (CK), regression kriging (RK) and residual maximum likelihood (REML)) in mapping the spatial distribution of SOC at a depth of 0-15 cm. Terrain attributes and the normalised difference vegetation index (NDVI) were used as ancillary variables. RESULTS: The distribution of SOC was significantly related to NDVI and terrain attributes. Furthermore, geostatistical analyses reflected a moderately structured spatial correlation of SOC. Regression analyses identified the NDVI and slope as the best predictors for describing the spatial pattern of SOC. Combined with NDVI and slope gradient, REML and RK performed better in increasing map prediction accuracy and decreasing the soothing effect of kriging. CONCLUSION: The spatial pattern of SOC was controlled by topography and cultivation activity. The predictive abilities of OK and CK were limited. Combined with the auxiliary variables, REML and RK can improve the prediction accuracy. This study is beneficial for the further research of precise SOC management in the typical karst landscape. PMID- 22297928 TI - Poles apart. PMID- 22297929 TI - The low-level nuclear threat. PMID- 22297930 TI - Damage limitation. PMID- 22297931 TI - Global health hits crisis point. PMID- 22297943 TI - The great Arctic oil race begins. PMID- 22297944 TI - Diagnostics tome comes under fire. PMID- 22297945 TI - Stem-cell agency faces budget dilemma. PMID- 22297946 TI - Informed consent on trial. PMID- 22297947 TI - Dipole hunt stuck in neutral. PMID- 22297948 TI - Genomics ace quits Japan. PMID- 22297949 TI - Japan plans to merge major science bodies. PMID- 22297950 TI - Marine ecology: Attack of the blobs. PMID- 22297951 TI - Vaccine development: Man vs MRSA. PMID- 22297952 TI - Public health: The toxic truth about sugar. PMID- 22297953 TI - Conservation: Bring elephants to Australia? PMID- 22297955 TI - Literature: Wonders and ologies. PMID- 22297957 TI - Asian medicine: A fungus in decline. PMID- 22297958 TI - Asian medicine: Many unique types. PMID- 22297959 TI - Regulation: Safety-test initiatives for nanomaterials. PMID- 22297960 TI - Asian medicine: Call for more safety data. PMID- 22297961 TI - Asian medicine: Japan's paradigm. PMID- 22297962 TI - Asian medicine: Protect rare plants. PMID- 22297963 TI - Philip D. Lawley (1927-2011). PMID- 22297964 TI - Volcanology: Greek inflation circa 1600 BC. PMID- 22297965 TI - Neuroscience: Reward alters specific connections. PMID- 22297966 TI - Surface chemistry: Crystal cuts on the nanoscale. PMID- 22297968 TI - Molecular motors: A staggering giant. PMID- 22297969 TI - Precision measurement: A comb in the extreme ultraviolet. PMID- 22297970 TI - Quantum-coherent coupling of a mechanical oscillator to an optical cavity mode. AB - Optical laser fields have been widely used to achieve quantum control over the motional and internal degrees of freedom of atoms and ions, molecules and atomic gases. A route to controlling the quantum states of macroscopic mechanical oscillators in a similar fashion is to exploit the parametric coupling between optical and mechanical degrees of freedom through radiation pressure in suitably engineered optical cavities. If the optomechanical coupling is 'quantum coherent' -that is, if the coherent coupling rate exceeds both the optical and the mechanical decoherence rate--quantum states are transferred from the optical field to the mechanical oscillator and vice versa. This transfer allows control of the mechanical oscillator state using the wide range of available quantum optical techniques. So far, however, quantum-coherent coupling of micromechanical oscillators has only been achieved using microwave fields at millikelvin temperatures. Optical experiments have not attained this regime owing to the large mechanical decoherence rates and the difficulty of overcoming optical dissipation. Here we achieve quantum-coherent coupling between optical photons and a micromechanical oscillator. Simultaneously, coupling to the cold photon bath cools the mechanical oscillator to an average occupancy of 1.7 +/- 0.1 motional quanta. Excitation with weak classical light pulses reveals the exchange of energy between the optical light field and the micromechanical oscillator in the time domain at the level of less than one quantum on average. This optomechanical system establishes an efficient quantum interface between mechanical oscillators and optical photons, which can provide decoherence-free transport of quantum states through optical fibres. Our results offer a route towards the use of mechanical oscillators as quantum transducers or in microwave to-optical quantum links. PMID- 22297971 TI - Direct frequency comb spectroscopy in the extreme ultraviolet. AB - The development of the optical frequency comb (a spectrum consisting of a series of evenly spaced lines) has revolutionized metrology and precision spectroscopy owing to its ability to provide a precise and direct link between microwave and optical frequencies. A further advance in frequency comb technology is the generation of frequency combs in the extreme-ultraviolet spectral range by means of high-harmonic generation in a femtosecond enhancement cavity. Until now, combs produced by this method have lacked sufficient power for applications, a drawback that has also hampered efforts to observe phase coherence of the high-repetition rate pulse train produced by high-harmonic generation, which is an extremely nonlinear process. Here we report the generation of extreme-ultraviolet frequency combs, reaching wavelengths of 40 nanometres, by coupling a high-power near infrared frequency comb to a robust femtosecond enhancement cavity. These combs are powerful enough for us to observe single-photon spectroscopy signals for both an argon transition at 82 nanometres and a neon transition at 63 nanometres, thus confirming the combs' coherence in the extreme ultraviolet. The absolute frequency of the argon transition has been determined by direct frequency comb spectroscopy. The resolved ten-megahertz linewidth of the transition, which is limited by the temperature of the argon atoms, is unprecedented in this spectral region and places a stringent upper limit on the linewidth of individual comb teeth. Owing to the lack of continuous-wave lasers, extreme-ultraviolet frequency combs are at present the only promising route to extending ultrahigh-precision spectroscopy to the spectral region below 100 nanometres. At such wavelengths there is a wide range of applications, including the spectroscopy of electronic transitions in molecules, experimental tests of bound-state and many-body quantum electrodynamics in singly ionized helium and neutral helium, the development of next-generation 'nuclear' clocks and searches for variation of fundamental constants using the enhanced sensitivity of highly charged ions. PMID- 22297972 TI - Nonlinear material behaviour of spider silk yields robust webs. AB - Natural materials are renowned for exquisite designs that optimize function, as illustrated by the elasticity of blood vessels, the toughness of bone and the protection offered by nacre. Particularly intriguing are spider silks, with studies having explored properties ranging from their protein sequence to the geometry of a web. This material system, highly adapted to meet a spider's many needs, has superior mechanical properties. In spite of much research into the molecular design underpinning the outstanding performance of silk fibres, and into the mechanical characteristics of web-like structures, it remains unknown how the mechanical characteristics of spider silk contribute to the integrity and performance of a spider web. Here we report web deformation experiments and simulations that identify the nonlinear response of silk threads to stress- involving softening at a yield point and substantial stiffening at large strain until failure--as being crucial to localize load-induced deformation and resulting in mechanically robust spider webs. Control simulations confirmed that a nonlinear stress response results in superior resistance to structural defects in the web compared to linear elastic or elastic-plastic (softening) material behaviour. We also show that under distributed loads, such as those exerted by wind, the stiff behaviour of silk under small deformation, before the yield point, is essential in maintaining the web's structural integrity. The superior performance of silk in webs is therefore not due merely to its exceptional ultimate strength and strain, but arises from the nonlinear response of silk threads to strain and their geometrical arrangement in a web. PMID- 22297973 TI - Decadal to monthly timescales of magma transfer and reservoir growth at a caldera volcano. AB - Caldera-forming volcanic eruptions are low-frequency, high-impact events capable of discharging tens to thousands of cubic kilometres of magma explosively on timescales of hours to days, with devastating effects on local and global scales. Because no such eruption has been monitored during its long build-up phase, the precursor phenomena are not well understood. Geophysical signals obtained during recent episodes of unrest at calderas such as Yellowstone, USA, and Campi Flegrei, Italy, are difficult to interpret, and the conditions necessary for large eruptions are poorly constrained. Here we present a study of pre-eruptive magmatic processes and their timescales using chemically zoned crystals from the 'Minoan' caldera-forming eruption of Santorini volcano, Greece, which occurred in the late 1600s BC. The results provide insights into how rapidly large silicic systems may pass from a quiescent state to one on the edge of eruption. Despite the large volume of erupted magma (40-60 cubic kilometres), and the 18,000-year gestation period between the Minoan eruption and the previous major eruption, most crystals in the Minoan magma record processes that occurred less than about 100 years before the eruption. Recharge of the magma reservoir by large volumes of silicic magma (and some mafic magma) occurred during the century before eruption, and mixing between different silicic magma batches was still taking place during the final months. Final assembly of large silicic magma reservoirs may occur on timescales that are geologically very short by comparison with the preceding repose period, with major growth phases immediately before eruption. These observations have implications for the monitoring of long-dormant, but potentially active, caldera systems. PMID- 22297974 TI - Serial translocation by means of circular intermediates underlies colour sidedness in cattle. AB - Colour sidedness is a dominantly inherited phenotype of cattle characterized by the polarization of pigmented sectors on the flanks, snout and ear tips. It is also referred to as 'lineback' or 'witrik' (which means white back), as colour sided animals typically display a white band along their spine. Colour sidedness is documented at least since the Middle Ages and is presently segregating in several cattle breeds around the globe, including in Belgian blue and brown Swiss. Here we report that colour sidedness is determined by a first allele on chromosome 29 (Cs(29)), which results from the translocation of a 492-kilobase chromosome 6 segment encompassing KIT to chromosome 29, and a second allele on chromosome 6 (Cs(6)), derived from the first by repatriation of fused 575 kilobase chromosome 6 and 29 sequences to the KIT locus. We provide evidence that both translocation events involved circular intermediates. This is the first example, to our knowledge, of a phenotype determined by homologous yet non syntenic alleles that result from a novel copy-number-variant-generating mechanism. PMID- 22297978 TI - Rice wine intoxication in a nondrinker. PMID- 22297979 TI - A Hoxb13-driven reverse tetracycline transactivator system for conditional gene expression in the prostate. AB - BACKGROUND: Genetically engineered mouse models play important roles in analyses of prostate development and pathobiology. While constitutive genetic gain- and loss-of-function models have contributed significantly to our understanding of molecular events driving these processes, the availability of a tightly regulated inducible expression system could extend the utility of transgenic approaches. Here, we describe the development of a Tet-regulatory system that employs Hoxb13 transcriptional control elements to direct reverse tetracycline transactivator (rtTA) expression in the prostate. METHODS: Using recombineering technology, the rtTA gene was placed under Hoxb13 cis-regulatory transcriptional control in the context of a 218-kb bacterial artificial chromosome. F(1) offspring carrying the Hoxb13-rtTA transgene were bred to a Tetracycline operator-Histone 2B-Green Fluorescent Protein (TetO-H2BGFP) responder line. Detailed reporter gene expression analyses, including doxycycline (Dox) induction and withdrawal kinetics, were performed in Hoxb13-rtTA|TetO-H2BGFP double transgenic adult mice and embryos. RESULTS: Dox-dependent GFP expression was observed exclusively in the prostate and distal colon epithelia of double transgenic mice. Reporter gene mRNA was detected in the prostate within 6 hr of Dox exposure, and was extinguished within 24 hr after Dox withdrawal. Furthermore, Dox-induced reporter gene expression persisted after castration. CONCLUSIONS: The Hoxb13-rtTA transgenic system provides a powerful tool for conditional Tet operator-driven transgene expression in the normal prostate and during disease progression. Used in conjunction with other prostate pathology models, these mice will enable precise, temporally controlled analyses of gene function and can provide opportunities for detailed analyses of molecular events underlying prostate diseases. PMID- 22297980 TI - Structure of human tankyrase 1 in complex with small-molecule inhibitors PJ34 and XAV939. AB - The crystal structures of tankyrase 1 (TNKS1) in complex with two small-molecule inhibitors, PJ34 and XAV939, both at 2.0 A resolution, are reported. The structure of TNKS1 in complex with PJ34 reveals two molecules of PJ34 bound in the NAD(+) donor pocket. One molecule is in the nicotinamide portion of the pocket, as previously observed in other PARP structures, while the second molecule is bound in the adenosine portion of the pocket. Additionally, unlike the unliganded crystallization system, the TNKS1-PJ34 crystallization system has the NAD(+) donor site accessible to bulk solvent in the crystal, which allows displacement soaking. The TNKS1-PJ34 crystallization system was used to determine the structure of TNKS1 in complex with XAV939. These structures provide a basis for the start of a structure-based drug-design campaign for TNKS1. PMID- 22297981 TI - Room-temperature ultrahigh-resolution time-of-flight neutron and X-ray diffraction studies of H/D-exchanged crambin. AB - The room-temperature (RT) X-ray structure of H/D-exchanged crambin is reported at 0.85 A resolution. As one of the very few proteins refined with anisotropic atomic displacement parameters at two temperatures, the dynamics of atoms in the RT and 100 K structures are compared. Neutron diffraction data from an H/D exchanged crambin crystal collected at the Protein Crystallography Station (PCS) showed diffraction beyond 1.1 A resolution. This is the highest resolution neutron diffraction reported to date for a protein crystal and will reveal important details of the anisotropic motions of H and D atoms in protein structures. PMID- 22297982 TI - Structures of new crystal forms of Mycobacterium tuberculosis peptidyl-tRNA hydrolase and functionally important plasticity of the molecule. AB - The X-ray structures of new crystal forms of peptidyl-tRNA hydrolase from M. tuberculosis reported here and the results of previous X-ray studies of the enzyme from different sources provide a picture of the functionally relevant plasticity of the protein molecule. The new X-ray results confirm the connection deduced previously between the closure of the lid at the peptide-binding site and the opening of the gate that separates the peptide-binding and tRNA-binding sites. The plasticity of the molecule indicated by X-ray structures is in general agreement with that deduced from the available solution NMR results. The correlation between the lid and the gate movements is not, however, observed in the NMR structure. PMID- 22297983 TI - Structure of a pectin methylesterase from Yersinia enterocolitica. AB - Pectin methylesterases (PMEs) are family 8 carbohydrate esterases (CE8s) which remove the methyl group from methylesterified galacturonic acid (GalA) residues within pectin. Although the role of pectinases such as PMEs within dedicated phytopathogens has been well established, the significance of homologous enzymes found within the genomes of human enteropathogens remains to be determined. Presented here is the low-resolution (3.5 A) structure of the CE8 from Yersinia enterocolitica (YeCE8). The high degree of structural conservation in the topology of the active-site cleft and catalytic apparatus that is shared with a characterized PME from a bacterial phytopathogen (i) indicates that YeCE8 is active on methylated pectin and (ii) highlights a more prominent role for pectin utilization in Yersinia than in other enteropathogenic species. PMID- 22297984 TI - A new crystal lattice structure of Helicobacter pylori neutrophil-activating protein (HP-NAP). AB - A new crystal lattice structure of Helicobacter pylori neutrophil-activating protein (HP-NAP) has been determined in two forms: the native state (Apo) at 2.20 A resolution and an iron-loaded form (Fe-load) at 2.50 A resolution. The highly solvated packing of the dodecameric shell is suitable for crystallographic study of the metal ion-uptake pathway. Like other bacterioferritins, HP-NAP forms a spherical dodecamer with 23 symmetry including two kinds of channels. Iron loading causes a series of conformational changes of amino-acid residues (Trp26, Asp52 and Glu56) at the ferroxidase centre. PMID- 22297985 TI - Three-dimensional structure of a thermophilic family GH11 xylanase from Thermobifida fusca. AB - Thermostable enzymes employ various structural features dictated at the amino acid sequence level that allow them to maintain their integrity at higher temperatures. Many hypotheses as to the nature of thermal stability have been proposed, including optimized core hydrophobicity and an increase in charged surface residues to enhance polar solvent interactions for solubility. Here, the three-dimensional structure of the family GH11 xylanase from the moderate thermophile Thermobifida fusca in its trapped covalent glycosyl-enzyme intermediate complex is presented. Interactions with the bound ligand show fewer direct hydrogen bonds from ligand to protein than observed in previous complexes from other species and imply that binding of the xylan substrate involves several water-mediated hydrogen bonds. PMID- 22297986 TI - Structure of the interleukin-2 tyrosine kinase Src homology 2 domain; comparison between X-ray and NMR-derived structures. AB - The crystal structure of the interleukin-2 tyrosine kinase Src homology domain (Itk SH2) is described and it is found that unlike in studies of this domain using NMR spectroscopy, cis-trans-prolyl isomerization is not readily detected in the crystal structure. Based on similarities between the Itk SH2 crystal form and the cis form of the Itk SH2 NMR structure, it is concluded that it is likely that the prolyl imide bond at least in part adopts the cis conformation in the crystal form. However, the lack of high-resolution data and the dynamic nature of the proline-containing loop mean that the precise imide-bond conformation cannot be determined and prolyl cis-trans isomerization in the crystal cannot be ruled out. Given the preponderance of structures that have been solved by X-ray crystallography in the Protein Data Bank, this result supports the notion that prolyl isomerization in folded proteins has been underestimated among known structures. Interestingly, while the precise status of the proline residue is ambiguous, Itk SH2 crystallizes as a domain-swapped dimer. The domain-swapped structure of Itk SH2 is similar to the domain-swapped SH2 domains of Grb2 and Nck, with domain swapping occurring at the beta-meander region of all three SH2 domains. Thus, for Itk SH2 structural analysis by NMR spectroscopy and X-ray crystallography revealed very different structural features: proline isomerization versus domain-swapped dimerization, respectively. PMID- 22297987 TI - Lysozyme contamination facilitates crystallization of a heterotrimeric cortactin Arg-lysozyme complex. AB - Crystallization of contaminating proteins is a frequently encountered problem for macromolecular crystallographers. In this study, an attempt was made to obtain a binary cocrystal structure of the SH3 domain of cortactin and a 17-residue peptide from the Arg nonreceptor tyrosine kinase encompassing a PxxPxxPxxP (PxxP1) motif. However, cocrystals could only be obtained in the presence of trace amounts of a contaminating protein. A structure solution obtained by molecular replacement followed by ARP/wARP automatic model building allowed a 'sequence-by-crystallography' approach to discover that the contaminating protein was lysozyme. This 1.65 A resolution crystal structure determination of a 1:1:1 heterotrimeric complex of Arg, cortactin and lysozyme thus provides an unusual 'caveat emptor' warning of the dangers that underpurified proteins harbor for macromolecular crystallographers. PMID- 22297988 TI - Cloning, purification, crystallization and preliminary X-ray diffraction analysis of mouse PACSIN 3 protein. AB - PACSIN-family proteins are cytoplasmic proteins that have vesicle-transport, membrane-dynamics, actin-reorganization and microtubule activities. Here, the N terminal F-BAR domain of mouse PACSIN 3, which contains 341 amino acids, was successfully cloned, purified and crystallized. The crystal of PACSIN 3 (1-341) diffracted to 2.6 A resolution and belonged to space group P2(1), with unit-cell parameters a = 46.9, b = 54.7, c = 193.7 A, alpha = 90, beta = 96.9, gamma = 90 degrees . These data should provide further information on PACSIN-family protein structures. PMID- 22297989 TI - Expression, purification, crystallization and preliminary crystallographic analysis of a thermostable DNA ligase from the archaeon Thermococcus sibiricus. AB - DNA ligases join single-strand breaks in double-stranded DNA by catalyzing the formation of a phosphodiester bond between adjacent 5'-phosphate and 3'-hydroxyl termini. Their function is essential to maintain the integrity of the genome in DNA replication, recombination and repair. A recombinant ATP-dependent DNA ligase from the hyperthermophilic anaerobic archaeon Thermococcus sibiricus was expressed in Escherichia coli and purified. Crystals were grown by vapour diffusion using the hanging-drop method with 17%(w/v) PEG 4000 and 8.5%(v/v) 2 propanol as precipitants. A diffraction experiment was performed with a single crystal, which diffracted X-rays to 3.0 A resolution. The crystal belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 58.590, b = 87.540, c = 126.300 A. PMID- 22297990 TI - Crystallization of the C-terminal domain of the bacteriophage T7 fibre protein gp17. AB - Bacteriophage T7 attaches to its host using the C-terminal domains of its six fibres, which are trimers of the gp17 protein. A C-terminal fragment of gp17 consisting of amino acids 371-553 has been expressed, purified and crystallized. Crystals of two forms were obtained, belonging to space group P2(1)2(1)2(1) (unit cell parameters a = 61.2, b = 86.0, c = 118.4 A) and space group C222(1) (unit cell parameters a = 68.3, b = 145.6, c = 172.1 A). They diffracted to 1.9 and 2.0 A resolution, respectively. Both crystals are expected to contain one trimer in the asymmetric unit. Multiwavelength anomalous dispersion phasing with a mercury derivative is in progress. PMID- 22297991 TI - Crystallization and preliminary X-ray diffraction analysis of the metalloregulatory protein DtxR from Thermoplasma acidophilum. AB - The diphtheria toxin repressor (DtxR) is a metal-ion-dependent transcriptional regulator which regulates genes encoding proteins involved in metal-ion uptake to maintain metal-ion homeostasis. DtxR from Thermoplasma acidophilum was cloned and overexpressed in Escherichia coli. Crystals of N-terminally His-tagged DtxR were obtained by hanging-drop vapour diffusion and diffracted to 1.8 A resolution. DtxR was crystallized at 296 K using polyethylene glycol 4000 as a precipitant. The crystals belonged to the orthorhombic space group P2(1)2(1)2, with unit-cell parameters a = 61.14, b = 84.61, c = 46.91 A, alpha = beta = gamma = 90 degrees . The asymmetric unit contained approximately one monomer of DtxR, giving a crystal volume per mass (V(M)) of 2.22 A(3) Da(-1) and a solvent content of 44.6%. PMID- 22297992 TI - Crystallization and preliminary crystallographic analysis of LipC12, a true lipase isolated through a metagenomics approach. AB - LipC12, a true lipase from family I.1 of bacterial lipases which was previously isolated through a metagenomics approach, contains 293 amino acids. Among lipases of known three-dimensional structure, it has a sequence identity of 47% to the lipase from Pseudomonas aeruginosa PAO1. Recombinant N-terminally His(6)-tagged LipC12 protein was expressed in Escherichia coli, purified in a homogenous form and crystallized in several conditions, with the best crystals being obtained using 2.0 M sodium formate and 0.1 M bis-tris propane pH 7.0. X-ray diffraction data were collected to 2.70 A resolution. The crystals belonged to the tetragonal space group P4(1)22, with unit-cell parameters a = b = 58.62, c = 192.60 A. PMID- 22297993 TI - Purification, crystallization and preliminary X-ray crystallographic studies of the Mycobacterium tuberculosis DNA gyrase CTD. AB - Mycobacterium tuberculosis DNA gyrase, a nanomachine involved in regulation of DNA topology, is the only type II topoisomerase present in this organism and hence is the sole target of fluoroquinolone in the treatment of tuberculosis. The C-terminal domain (CTD) of the DNA gyrase A subunit possesses a unique feature, the ability to wrap DNA in a chiral manner, that plays an essential role during the catalytic cycle. A construct of 36 kDa corresponding to this domain has been overproduced, purified and crystallized. Diffraction data were collected to 1.55 A resolution. Cleavage of the N-terminal His tag was crucial for obtaining crystals. The crystals belonged to space group P2(1)2(1)2(1), with one molecule in the asymmetric unit and a low solvent content (33%). This is the first report of the crystallization and preliminary X-ray diffraction studies of a DNA gyrase CTD from a species that contains one unique type II topoisomerase. PMID- 22297994 TI - Expression, purification, crystallization and preliminary X-ray analysis of Pseudomonas aeruginosa PelD. AB - The production of the PEL polysaccharide in Pseudomonas aeruginosa requires the binding of bis-(3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP) to the cytoplasmic GGDEF domain of the inner membrane protein PelD. Here, the overexpression, purification and crystallization of a soluble construct of PelD that encompasses the GGDEF domain and a predicted GAF domain is reported. Diffraction-quality crystals were grown using the hanging-drop vapour-diffusion method. The crystals grew as flat plates, with unit-cell parameters a = 88.3, b = 114.0, c = 61.9 A, alpha = beta = gamma = 90.0 degrees . The PelD crystals exhibited the symmetry of space group P2(1)2(1)2 and diffracted to a minimum d spacing of 2.2 A. On the basis of the Matthews coefficient (V(M) = 2.29 A(3) Da( 1)), it was estimated that two molecules are present in the asymmetric unit. PMID- 22297995 TI - Crystallization of oligonucleotides containing A-rich repeats suggests a structural contribution to the autoregulation mechanism of PABP translation. AB - Eukaryotic poly(A)-binding protein (PABP) commonly binds to the 3'-UTR poly(A) tail of every mRNA, but it also binds to the 5'-UTR of PABP mRNA for autoregulation of its expression. In the sequence of the latter binding site, the contiguous A residues are segmented discretely by the insertion of short pyrimidine oligonucleotides as linkers, so that (A)(6-8) segments are repeated six times. This differs from the poly(A)-tail sequence, which has a higher binding affinity for PABP. In order to examine whether the A-rich repeats have a functional structure, several RNA/DNA analogues were subjected to crystallization. It was found that some of them could be crystallized. Single crystals thus obtained diffracted to 4.1 A resolution. The fact that the repeated sequences can be crystallized suggests the possibility that the autoregulatory sequence in PABP mRNA has a specific structure which impedes the binding of PABP. When PABP is excessively produced, it could bind to this sequence by releasing the structure in order to interfere with initiation-complex formation for suppression of PABP translation. Otherwise, PABP at low concentration preferentially binds to the poly(A) tail of PABP mRNA. PMID- 22297996 TI - Crystallization and X-ray diffraction analysis of chondroitin lyase from baculovirus: envelope protein ODV-E66. AB - Baculovirus envelope protein ODV-E66 (67-704), in which the N-terminal 66 amino acids are truncated, is a chondroitin lyase. It digests chondroitin and chondroitin 6-sulfate efficiently, but does not digest chondroitin 4-sulfate. This unique characteristic is useful for the preparation of specific chondroitin oligosaccharides and for investigation of the mechanism of baculovirus infection. ODV-E66 (67-704) was crystallized; the crystal diffracted to 1.8 A resolution and belonged to space group P6(2) or P6(4), with unit-cell parameters a = b = 113.5, c = 101.5 A. One molecule is assumed to be present per asymmetric unit, which gives a Matthews coefficient of 2.54 A(3) Da(-1). PMID- 22297997 TI - Crystallization and preliminary X-ray crystallographic analysis of dioscorin from Dioscorea japonica. AB - Dioscorin, the major tuber storage protein in yam, has been reported to possess carbonic anhydrase, trypsin inhibitor, angiotensin-converting enzyme (ACE) inhibitor, free-radical scavenger, dehydroascorbate reductase and monodehydroascorbate reductase activities. Recent research has also found that dioscorin can enhance immune modulation via the toll-like receptor 4 (TLR-4) signal transduction pathway in RAW 264.7 cells, murine bone-marrow cells and human monocytes ex vivo. Resolving the structure of dioscorin would help in better understanding its activities and would provide clues to understanding the mechanism of its multiple functions. The full-length protein (residues 1-246) with an additional His(6) tag at the N-terminus was expressed in Escherichia coli Rosetta (DE3) cells. After His-tag cleavage and purification, the protein was crystallized by the sitting-drop vapour-diffusion method at 278 K. An X-ray diffraction data set was collected to a resolution of 2.11 A using a synchrotron X-ray source. The crystal belonged to space group C222(1), with unit-cell parameters a = 83.5, b = 156.8, c = 83.6 A, and was estimated to contain two protein molecules per asymmetric unit. PMID- 22297998 TI - Purification, crystallization and preliminary X-ray characterization of Bacillus cereus arylamine N-acetyltransferase 3 [(BACCR)NAT3]. AB - Arylamine N-acetyltransferases (NATs) are xenobiotic metabolizing enzymes (XMEs) that catalyze the acetylation of arylamines. All functional NATs described to date possess a strictly conserved Cys-His-Asp catalytic triad. Here, the purification, crystallization and preliminary X-ray characterization of Bacillus cereus arylamine N-acetyltransferase 3 [(BACCR)NAT3], a putative NAT isoenzyme that possesses a unique catalytic triad containing a glutamate residue, is reported. The crystal diffracted to 2.42 A resolution and belonged to the monoclinic space group C121, with unit-cell parameters a = 90.44, b = 44.52, c = 132.98 A, beta = 103.8 degrees . PMID- 22297999 TI - Crystallization and preliminary X-ray analysis of S-ribosylhomocysteinase from Streptococcus mutans. AB - S-Ribosylhomocysteinase (LuxS) encoded by the luxS gene from Streptococcus mutans plays a crucial role in the quorum-sensing system. LuxS was solubly expressed in Escherichia coli with high yield. The purity of the purified target protein, which was identified by SDS-PAGE and MALDI-TOF MS analysis, was >95%. The protein was crystallized using the hanging-drop vapour-diffusion method with PEG 3350 as the primary precipitant. X-ray diffraction data were collected at Beijing Synchrotron Radiation Facility (BSRF). Diffraction by the crystal extended to 2.4 A resolution and the crystal belonged to space group C222(1), with unit-cell parameters a = 55.3, b = 148.7, c = 82.8 A. PMID- 22298000 TI - Crystallization and preliminary X-ray diffraction analysis of Bacillus subtilis YwfE, an L-amino-acid ligase. AB - Bacillus subtilis YwfE, an L-amino-acid ligase, catalyzes the formation of an alpha-dipeptide from L-amino acids in an ATP-dependent manner. In order to elucidate the substrate-recognition mode and the reaction mechanism of this ligase, native and selenomethionine-derivatized (SeMet) crystals of YwfE in the presence of ADP, MgCl(2) and the dipeptide L-Ala-L-Gln were obtained using the hanging-drop vapour-diffusion method. These crystals diffracted to 1.9 and 2.8 A resolution, respectively. Preliminary SAD phase calculations using the data set from the SeMet crystal suggested that the crystal belonged to the hexagonal space group P6(5)22, with unit-cell parameters a = b = 90.85, c = 250.31 A, and contained one molecule in the asymmetric unit with a solvent content of 57.3%. PMID- 22298001 TI - Cloning, expression, crystallization and preliminary X-ray crystallographic analysis of aspartyl aminopeptidase from the apeB gene of Pseudomonas aeruginosa. AB - Aminopeptidases (APs) are a group of exopeptidases that catalyze the removal of amino acids from the N-termini of proteins and peptides. The APs are ubiquitous in nature and are of critical biological and medical importance because of their key role in protein degradation. Pseudomonas aeruginosa aspartyl aminopeptidase (PaAAP), which is encoded by the apeB gene, was expressed in Escherichia coli, purified and crystallized using the microbatch method. A preliminary structural study has been performed using the X-ray crystallographic method. The PaAAP crystal diffracted to 2.0 A resolution and belonged to the rhombohedral space group H3, with unit-cell parameters a = b = 133.6, c = 321.2. The unit-cell volume of the crystal is compatible with the presence of four monomers in the asymmetric unit, with a corresponding Matthews coefficient V(M) of 2.95 A(3) Da( 1) and a solvent content of 58.3%. PMID- 22298002 TI - Crystallization and preliminary X-ray diffraction analysis of an L-amino-acid oxidase from Bothrops jararacussu venom. AB - Snake-venom L-amino-acid oxidases (SV-LAAOs) trigger a wide range of local and systematic effects, including inhibition of platelet aggregation, cytotoxicity, haemolysis, apoptosis and haemorrhage. These effects mainly arise from the uncontrolled release of the hydrogen peroxide that is produced by the redox reaction involving L-amino acids catalyzed by these flavoenzymes. Taking their clinical relevance into account, few SV-LAAOs have been structurally characterized and the structural determinants responsible for their broad direct and indirect pharmacological activities remain unclear. In this work, an LAAO from Bothrops jararacussu venom (BJu-LAAO) was purified and crystallized. The BJu LAAO crystals belonged to space group P2(1), with unit-cell parameters a = 66.38, b = 72.19, c = 101.53 A, beta = 90.9 degrees . The asymmetric unit contained two molecules and the structure was determined and partially refined at 3.0 A resolution. PMID- 22298003 TI - Crystallization and preliminary X-ray diffraction analysis of human dipeptidyl peptidase 10 (DPPY), a component of voltage-gated potassium channels. AB - Dipeptidyl peptidase 10 (DPP10, DPPY) is an inactive peptidase associated with voltage-gated potassium channels, acting as a modulator of their electrophysiological properties, cell-surface expression and subcellular localization. Because potassium channels are important disease targets, biochemical and structural characterization of their interaction partners was sought. DPP10 was cloned and expressed using an insect-cell system and the protein was purified via His-tag affinity and size-exclusion chromatography. Crystals obtained by the sitting-drop method were orthorhombic, belonging to space group P2(1)2(1)2(1) with unit-cell parameters a = 80.91, b = 143.73, c = 176.25 A. A single solution with two molecules in the asymmetric unit was found using the structure of DPP6 (also called DPPX; PDB entry 1xfd) as the search model in a molecular replacement protocol. PMID- 22298004 TI - Expression, purification and preliminary structural analysis of the coiled-coil domain of Deinococcus radiodurans RecN. AB - Deinococcus radiodurans has developed an efficient mechanism which allows the integrity of its entire genome to be fully restored after exposure to very high doses of ionizing radiation. Homologous recombination plays a crucial role in this process. RecN is a protein that belongs to the SMC-like protein family and is suggested to be involved in DNA repair. RecN is composed of a globular domain and an antiparallel coiled-coil region which connects the N- and C-termini. It has been suggested that dimerization of RecN occurs via the coiled-coil domain, but to date there is no structural or biochemical evidence for this. Here, SAXS studies and preliminary X-ray diffraction data of crystals of the purified coiled coil domain of RecN are presented. The structure was solved by single-wavelength anomalous dispersion using SeMet derivatives, and preliminary electron-density maps support the rod-like model derived from the SAXS data. Model building and refinement are still ongoing. PMID- 22298005 TI - Crystallization and X-ray diffraction analysis of a novel surface-adhesin protein: protein E from Haemophilus influenzae. AB - Protein E (PE) is a ubiquitous multifunctional surface protein of Haemophilus spp. and other bacterial pathogens of the Pasteurellaceae family. H. influenzae utilizes PE for attachment to respiratory epithelial cells. In addition, PE interacts directly with plasminogen and the extracellular matrix (ECM) components vitronectin and laminin. Vitronectin is a complement regulator that inhibits the formation of the membrane-attack complex (MAC). PE-mediated vitronectin recruitment at the H. influenzae surface thus inhibits MAC and protects against serum bactericidal activity. Laminin is an abundant ECM protein and is present in the basement membrane that helps in adherence of H. influenzae during colonization. Here, the expression, purification and crystallization of and the collection of high-resolution data for this important H. influenzae adhesin are reported. To solve the phase problem for PE, Met residues were introduced and an SeMet variant was expressed and crystallized. Both native and SeMet-containing PE gave plate-like crystals in space group P2(1), with unit-cell parameters a = 44, b = 57, c = 61 A, beta = 96 degrees . Diffraction data collected from native and SeMet-derivative crystals extended to resolutions of 1.8 and 2.6 A, respectively. PMID- 22298006 TI - Crystallization and preliminary X-ray analysis of the Clostridium botulinum type D nontoxic nonhaemagglutinin. AB - Clostridium botulinum produces botulinum neurotoxin (BoNT) as a large toxin complex assembled with nontoxic nonhaemagglutinin (NTNHA) and/or haemagglutinin components. Complex formation with NTNHA is considered to be critical in eliciting food poisoning because the complex shields the BoNT from the harsh conditions in the digestive tract. In the present study, NTNHA was expressed in Escherichia coli and crystallized. Diffraction data were collected to 3.9 A resolution. The crystal belonged to the trigonal space group P321 or P3(1)21/P3(2)21, with unit-cell parameters a = b = 147.85, c = 229.74 A. The structure of NTNHA will provide insight into the assembly mechanism that produces the unique BoNT-NTNHA complex. PMID- 22298007 TI - Refolding, purification and crystallization of the FrpB outer membrane iron transporter from Neisseria meningitidis. AB - FrpB is an integral outer membrane protein from the human pathogen Neisseria meningitidis. It is a member of the TonB-dependent transporter family and promotes the uptake of iron across the outer membrane. There is also evidence that FrpB is an antigen and hence a potential component of a vaccine against meningococcal meningitis. FrpB incorporating a polyhistidine tag was overexpressed in Escherichia coli into inclusion bodies. The protein was then solubilized in urea, refolded and purified to homogeneity. Two separate antigenic variants of FrpB were crystallized by sitting-drop vapour diffusion. Crystals of the F5-1 variant diffracted to 2.4 A resolution and belonged to space group C2, with unit-cell parameters a = 176.5, b = 79.4, c = 75.9 A, beta = 98.3 degrees . Crystal-packing calculations suggested the presence of a monomer in the asymmetric unit. Crystals of the F3-3 variant also diffracted to 2.4 A resolution and belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 85.3, b = 104.6, c = 269.1 A. Preliminary analysis suggested the presence of an FrpB trimer in the asymmetric unit. PMID- 22298008 TI - Purification, crystallization and preliminary X-ray diffraction analysis of the Hsp40 protein CPIP1 from Nicotiana tabacum. AB - Chaperones promote many different molecular processes, including the folding, targeting and degradation of proteins. The best-studied chaperone system consists of the Hsp70s and their co-chaperones the Hsp40s. Chaperone function can be hijacked by viruses in plants. Potato virus Y interacts via its coat protein with an Hsp40 from Nicotiana tabacum, referred to as NtCPIP1, in order to regulate replication. To understand the molecular determinants of this mechanism, different variants of NtCPIP1 were expressed, purified and crystallized. While crystals of wild-type NtCPIP1 diffracted to 8.0 A resolution, the deletion mutant NtCPIP1-Delta(1:127) crystallized in space group P2(1)2(1)2 and diffracted to 2.4 A resolution. PMID- 22298009 TI - Expression, purification, crystallization and preliminary X-ray diffraction analysis of a ribokinase from the thermohalophile Halothermothrix orenii. AB - A ribokinase gene (rbk) from the anaerobic halothermophilic bacterium Halothermothrix orenii was cloned and overexpressed in Escherichia coli. The recombinant protein (Ho-Rbk) was purified using immobilized metal-ion affinity chromatography and crystals were obtained using the sitting-drop method. Diffraction data were collected to a resolution of 3.1 A using synchrotron radiation. The crystals belonged to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 45.6, b = 61.1, c = 220.2, and contained two molecules per asymmetric unit. A molecular-replacement solution has been found and attempts are currently under way to build a model of the ribokinase. Efforts to improve crystal quality so that higher resolution data can be obtained are also being considered. PMID- 22298010 TI - Crystallization and preliminary X-ray diffraction analysis of orotate phosphoribosyltransferase from the human malaria parasite Plasmodium falciparum. AB - Orotate phosphoribosyltransferase (OPRT) catalyzes the Mg(2+)-dependent condensation of orotic acid (OA) with 5-alpha-D-phosphorylribose 1-diphosphate (PRPP) to yield diphosphate (PP(i)) and the nucleotide orotidine 5' monophosphate. OPRT from Plasmodium falciparum produced in Escherichia coli was crystallized by the sitting-drop vapour-diffusion method in complex with OA and PRPP in the presence of Mg(2+). The crystal exhibited tetragonal symmetry, belonging to space group P4(1) or P4(3), with unit-cell parameters a = b = 49.15, c = 226.94 A. X-ray diffraction data were collected to 2.5 A resolution at 100 K using a synchrotron-radiation source. PMID- 22298012 TI - Factors determining visual outcome in endogenous Candida endophthalmitis. AB - PURPOSE: To determine factors affecting the visual outcome of eyes with endogenous Candida endophthalmitis. METHODS: Retrospective cohort study of 44 eyes from 36 patients diagnosed with candida endophthalmitis at 2 tertiary referral uveitis centers. Outcome measures included the development of retinal detachment and the occurrence of visual loss (visual acuity of <20/40) and severe visual loss (visual acuity of <= 20/200). RESULTS: Twenty four of 44 eyes (55%) had visual loss and 16 of 44 eyes (32%) had severe visual loss by the end of the study. Early vitrectomy significantly reduced the risk of retinal detachment (P = 0.02). Factors associated with poor visual outcome included poor presenting visual acuity (relative risk = 2.38; 95% confidence interval, 1.01-5.55; P < 0.05) and centrally located fungal lesions (relative risk = 5.01; 95% confidence interval, 1.00-2.52; P < 0.05). CONCLUSION: Candida endophthalmitis is associated with a high rate of visual loss, particularly in patients with poor presenting visual acuity or centrally located lesions. Early vitrectomy reduces the risk of retinal detachment. PMID- 22298013 TI - Anatomical and visual results of transconjunctival sutureless vitrectomy using subconjunctival anesthesia performed on select patients taking anticoagulant and antiplatelet agents. AB - PURPOSE: The purpose of this study was to report the observed outcomes of anticoagulated patients undergoing transconjunctival sutureless vitrectomies using subconjunctival anesthesia without preoperative cessation of anticoagulation and antiplatelet (AC/AP) agents. METHODS: A retrospective chart review was performed on patients taking AC/AP agents who were undergoing transconjunctival sutureless vitrectomies with subconjunctival anesthesia between January 2007 and June 2009. Intra- and postoperative complications (such as massive hemorrhage), anatomical results, satisfactory analgesia (informed by patients and recorded by surgeon), anatomical results, and visual acuity were documented. RESULTS: Sixty-three surgeries were performed on 56 eyes of 52 patients. Thirty-two patients were taking aspirin and clopidogrel, 18 were taking warfarin, 5 were taking clopidogrel, 3 were taking aspirin and warfarin, 2 were taking acetylsalicylic acid and dipyridamole, and 1 was taking warfarin and clopidogrel. All patients had satisfactory analgesia. No intraoperative complications occurred. Seven eyes (13%) had postoperative vitreous hemorrhage. Overall, 79% of patients had improved postoperative visual acuity, 16% of patients had unchanged visual acuity, and 5% of patients had worse visual acuity at last follow-up visit. CONCLUSION: Medical disease requiring systemic AC/AP therapy is often present in patients with vitreoretinal disease. Transconjunctival sutureless vitrectomies using subconjunctival anesthesia may be a safe and effective surgical option in select patients in whom cessation of AC/AP and/or delayed ophthalmic intervention is imprudent. PMID- 22298014 TI - OPTIMIZING INDIVIDUALIZED THERAPY WITH BEVACIZUMAB FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION. AB - PURPOSE: The purpose of this study was to evaluate a standardized retreatment strategy with intravitreal bevacizumab in the treatment of neovascular age related macular degeneration. METHODS: In this double-masked randomized trial, patients with neovascular age-related macular degeneration were randomized to intravitreous bevacizumab or standard care. Bevacizumab treatment was given at 6 weekly intervals with 3 consecutive injections (loading phase) followed by variable dosing to Week 54 using standardized retreatment criteria. RESULTS: Three hundred and eighty retreatment decisions were made after 3 fixed injections for 64 patients randomized to bevacizumab that completed 1-year follow-up. The most common criterion for retreatment was persistent intraretinal fluid on optical coherence tomography imaging, and fluorescein angiography did not drive any retreatment decision. The mean (median) change in visual acuity and optical coherence tomography central macular thickness after the 3 loading treatments to Week 54 was +0.4 (+1.0) letters and +2.0 (+1.0) MUm, respectively, with a mean (median) of 7.1 (7.0) injections. The median time to retreatment was 42 days with 12 of 69 injection-free episodes (17%) lasting more than 3 months. CONCLUSION: Sustained improvements in structure and function were achieved using this 6 weekly variable-dosing regimen with intravitreal bevacizumab. Most retreatment decisions were based on qualitative interpretation of optical coherence tomography scans. PMID- 22298015 TI - A spectral-domain optical coherence tomography description of ND: YAG laser hyaloidotomy in premacular subhyaloid hemorrhage. PMID- 22298016 TI - Re: "heavy silicone oil removal without a suction pump: a surgical technique". PMID- 22298017 TI - Differential impact of a Dutch alcohol prevention program targeting adolescents and parents separately and simultaneously: low self-control and lenient parenting at baseline predict effectiveness. AB - To test whether baseline levels of the factors accountable for the impact of the Prevention of Alcohol use in Students (PAS) intervention (self-control, perceived rules about alcohol and parental attitudes about alcohol), moderate the effect of the intervention. A cluster randomized trial including 3,490 Dutch early adolescents (M age=12.66, SD=.49) and their parents randomized over four conditions: 1) parent intervention, 2) student intervention, 3) combined intervention and 4) control group. Moderators at baseline were used to examine the differential effects of the interventions on onset of (heavy) weekly drinking at 34-month follow-up. The combined intervention was only effective in preventing weekly drinking among those adolescents who reported to have lower self-control and more lenient parents at baseline. No differential effect was found for the onset of heavy weekly drinking. No moderating roles of self-control and lenient parenting were found for the separate student and parent interventions regarding the onset of drinking. The combined intervention is more effective among adolescents with low-self control and lenient parents at baseline, both factors that were a specific target of the intervention. The relevance of targeting self control in adolescents and restrictive parenting is underlined. PMID- 22298018 TI - Intravital microscopy of the spleen: quantitative analysis of parasite mobility and blood flow. AB - The advent of intravital microscopy in experimental rodent malaria models has allowed major advances to the knowledge of parasite-host interactions. Thus, in vivo imaging of malaria parasites during pre-erythrocytic stages have revealed the active entrance of parasites into skin lymph nodes, the complete development of the parasite in the skin, and the formation of a hepatocyte-derived merosome to assure migration and release of merozoites into the blood stream. Moreover, the development of individual parasites in erythrocytes has been recently documented using 4D imaging and challenged our current view on protein export in malaria. Thus, intravital imaging has radically changed our view on key events in Plasmodium development. Unfortunately, studies of the dynamic passage of malaria parasites through the spleen, a major lymphoid organ exquisitely adapted to clear infected red blood cells are lacking due to technical constraints. Using the murine model of malaria Plasmodium yoelii in Balb/c mice, we have implemented intravital imaging of the spleen and reported a differential remodeling of it and adherence of parasitized red blood cells (pRBCs) to barrier cells of fibroblastic origin in the red pulp during infection with the non-lethal parasite line P.yoelii 17X as opposed to infections with the P.yoelii 17XL lethal parasite line. To reach these conclusions, a specific methodology using ImageJ free software was developed to enable characterization of the fast three-dimensional movement of single-pRBCs. Results obtained with this protocol allow determining velocity, directionality and residence time of parasites in the spleen, all parameters addressing adherence in vivo. In addition, we report the methodology for blood flow quantification using intravital microscopy and the use of different colouring agents to gain insight into the complex microcirculatory structure of the spleen. ETHICS STATEMENT: All the animal studies were performed at the animal facilities of University of Barcelona in accordance with guidelines and protocols approved by the Ethics Committee for Animal Experimentation of the University of Barcelona CEEA-UB (Protocol No DMAH: 5429). Female Balb/c mice of 6 8 weeks of age were obtained from Charles River Laboratories. PMID- 22298020 TI - Impending paradoxical thromboembolism: thrombus caught in transit. A case report. PMID- 22298019 TI - Chronic protection against ischemia and reperfusion-induced endothelial dysfunction during therapy with different organic nitrates. AB - INTRODUCTION: Ischemic and pharmacologic preconditioning have great clinical potential, but it remains unclear whether their effects can be maintained over time during repeated exposure.We have previously demonstrated that the acute protective effect of nitroglycerin (GTN) is attenuated during repeated daily administration. Pentaerythrityl tetranitrate (PETN) is an organic nitrate with different hemodynamic and biochemical properties. The purpose of the current experiment was to study the preconditioning-like effects of PETN and GTN during repeated daily exposure. METHODS AND RESULTS: In a randomized, investigator-blind parallel trial, 30 healthy (age 25-32) volunteers were randomized to receive (1) transdermal GTN (0.6 mg/h) administered for 2 h a day for 6 days; (2) oral PETN (80 mg) once a day for 6 days; or (3) no therapy. One week later, endothelium dependent flow-mediated dilation was assessed before and after exposure to ischemia and reperfusion (IR). IR caused a significant blunting of the endothelium-dependent relaxation in the control group (FMD before IR: 5.8 +/- 2.1%; after IR 1.0 +/- 2.1%; P < 0.01). Daily, 2-h exposure to GTN partially prevented IR-induced endothelial dysfunction (FMD before IR: 7.7 +/- 2.4%; after IR 4.3 +/- 3.0%; P < 0.01 compared to before IR). In contrast, daily PETN administration afforded greater protection from IR-induced endothelial injury (FMD before IR: 7.9 +/- 1.7%; after IR 6.4 +/- 5.3%, P = ns; P < 0.05 ANOVA across groups). In vitro, incubation of human endothelial cells with GTN (but not PETN) was associated with inhibition (P < 0.01) of aldehyde dehydrogenase, an enzyme that is important for both nitrate biotransformation and ischemic preconditioning. DISCUSSION: We previously showed that upon repeated administration, the preconditioning-like effects of GTN are attenuated. The present data demonstrate a gradient in the extent of protection afforded by the two nitrates, suggesting that PETN-induced preconditioning is maintained after prolonged administration in a human in vivo model of endothelial dysfunction induced by ischemia. Using isolated human endothelial cells, we propose a mechanistic explanation for this observation based on differential effects of GTN versus PETN on the activity of mitochondrial aldehyde dehydrogenase. PMID- 22298021 TI - Maternal Sjogren syndrome and isolated complete fetal av block: prenatal diagnosis and therapy. PMID- 22298023 TI - Mammalian zona pellucida glycoproteins: structure and function during fertilization. AB - Zona pellucida (ZP) is a glycoproteinaceous translucent matrix that surrounds the mammalian oocyte and plays a critical role in the accomplishment of fertilization. In humans, it is composed of 4 glycoproteins designated as ZP1, ZP2, ZP3 and ZP4, whereas mouse ZP is composed of ZP1, ZP2 and ZP3 (Zp4 being a pseudogene). In addition to a variable sequence identity of a given zona protein among various species, human ZP1 and ZP4 are paralogs and mature polypeptide chains share an identity of 47%. Employing either affinity purified native or recombinant human zona proteins, it has been demonstrated that ZP1, ZP3 and ZP4 bind to the capacitated human spermatozoa and induce an acrosome reaction, whereas in mice, ZP3 acts as the putative primary sperm receptor. Human ZP2 only binds to acrosome-reacted spermatozoa and thus may be acting as a secondary sperm receptor. In contrast to O-linked glycans of ZP3 in mice, N-linked glycans of human ZP3 and ZP4 are more relevant for induction of the acrosome reaction. Recent studies suggest that Sialyl-Lewis(x) sequence present on both N- and O glycans of human ZP play an important role in human sperm-egg binding. There are subtle differences in the downstream signaling events associated with ZP3 versus ZP1/ZP4-mediated induction of the acrosome reaction. For example, ZP3 but not ZP1/ZP4-mediated induction of the acrosome reaction is dependent on the activation of the Gi protein-coupled receptor. Thus, various studies suggest that, in contrast to mice, in humans more than one zona protein binds to spermatozoa and induces an acrosome reaction. PMID- 22298022 TI - Cellular and molecular basis for endometriosis-associated infertility. AB - Endometriosis is a gynecological disease characterized by the presence of endometrial glandular epithelial and stromal cells growing in the extra-uterine environment. The disease afflicts 10%-15% of menstruating women causing debilitating pain and infertility. Endometriosis appears to affect every part of a woman's reproductive system including ovarian function, oocyte quality, embryo development and implantation, uterine function and the endocrine system choreographing the reproductive process and results in infertility or spontaneous pregnancy loss. Current treatments are laden with menopausal-like side effects and many cause cessation or chemical alteration of the reproductive cycle, neither of which is conducive to achieving a pregnancy. However, despite the prevalence, physical and psychological tolls and health care costs, a cure for endometriosis has not yet been found. We hypothesize that endometriosis causes infertility via multifaceted mechanisms that are intricately interwoven thereby contributing to our lack of understanding of this disease process. Identifying and understanding the cellular and molecular mechanisms responsible for endometriosis-associated infertility might help unravel the confounding multiplicities of infertility and provide insights into novel therapeutic approaches and potentially curative treatments for endometriosis. PMID- 22298024 TI - A new resorufin-based spectroscopic probe for simple and sensitive detection of benzoyl peroxide via deboronation. AB - A new resorufin-based probe is developed, which exhibits a rapid and sensitive color and a fluorescence off-on response to benzoyl peroxide (BPO) in aqueous media containing 10% ethanol via deboronation. The probe has been applied to the simple detection of BPO in real samples such as wheat flour and antimicrobial agent. PMID- 22298025 TI - Quantifying and modeling the temperature-dependent gating of TRP channels. AB - The ability to sense environmental temperatures and to avoid noxious heat or cold is crucial for the survival of all organisms. In mammals, sensory neurons from dorsal root and trigeminal ganglia convey thermal information from the skin, mouth and nose to the central nervous system. Recent evidence has established that thermo TRPs, a subset of the TRP superfamily of cation channels, act as primary temperature sensors in cold-and-heat-sensitive neurons. The gating of these thermoTRPs exhibit strong temperature dependence, leading to steep changes in inward current upon heating or cooling. The origin of this striking temperature sensitivity remains incompletely understood. In this review, I propose criteria that define a thermoTRP, analyse the usefulness and limitations of the commonly used parameters thermal threshold and Q(10), provide an overview of possible thermodynamic principles and gating schemes for thermosensitive TRP channels, and perform a meta-analysis of publlished work on the molecular basis of heat sensitivity in TRPV1. This review may form a useful reference for the analysis and interpretation of further biophysical and structure-function studies dissecting the molecular basis of thermosensitivity in TRP channels. PMID- 22298026 TI - Bread supplemented with amaranth (Amaranthus cruentus): effect of phytates on in vitro iron absorption. AB - The objective of the present study was to evaluate the effect of the bread supplemented with whole amaranth flour (0, 20 and 40%) on iron bioavailability using Caco-2 cells model. The phytate and lower myo-inositol phosphates content in in vitro bread digests were measured by high pressure liquid chromatography. The breads made with amaranth showed significant increase of soluble phytates levels (up to 1.20 MUmol/g in dry matter for the 40% of substitution) in comparison with controls, which have not detectable values. A negative correlation among phytate and Fe availability was found when increased levels of amaranth.Ferritin concentration was found 2.7- and 2.0-fold higher (P<0.05) in cultures exposed to 20% and 40% of amaranth formulated bread samples, respectively, compared to control bread. The soluble phytate/Fe molar ratio explained the whole amaranth flour-mediated inhibitory effect associated to the limitation of available Fe; however, the use up to 20% of amaranth in bread formulation appears as a promising strategy to improve the nutritional value of bread, as indicated by the ferritin concentrations quantified in cell cultures. Higher proportion of amaranth flour increased Fe concentration although there was not detected any increase in Fe uptake. PMID- 22298027 TI - Maize prolamins resistant to peptic-tryptic digestion maintain immune-recognition by IgA from some celiac disease patients. AB - Maize is used as an alternative to wheat to elaborate food stuffs for celiac patients in a gluten-free diet.However, some maize prolamins (zeins) contain amino acid sequences that resemble the wheat gluten immunodominant peptides and their integrity after gastrointestinal proteolysisis unknown. In this study, the celiac IgA-immunoreactivity to zeins from raw or nixtamalized grains, before and after peptic/tryptic digestion was evaluated and their possible immunogenicity was investigated by in silico methods.IgA from some celiac patients with HLA-DQ2 or DQ8 haplotypes recognized two alpha-zeins even after peptic/ tryptic proteolysis. However, digestion affected zeins after denaturation, reduction, and alkylation, used for identification of prolamins as alpha-zein A20 and A30 by MS/MS sequencing. An in silico analysis indicated that other zeins contain similar sequences, or sequences that may bind even better to the HLA-DQ2/DQ8 molecules compared to the already identified ones. Results concur to indicate that relative abundance of these zeins, along with factors affecting their resistance to proteolysis, may be of paramount clinical relevance, and the use of maize in the formulation and preparation of gluten-free foods must be reevaluated in some cases of celiac disease. PMID- 22298028 TI - Who should we target for diabetes prevention and diabetes risk reduction? PMID- 22298029 TI - Engineering interfacial properties by anionic surfactant-chitosan complexes to improve stability of oil-in-water emulsions. AB - Oil-in-water emulsions (10% w/w n-tetradecane) were prepared at pH = 5.7 by using, as surface active agents, electrostatically formed complexes of sodium stearoyl lactylate (SSL) at a concentration of 0.4% (w/w) and chitosan (CH) in a concentration range between 0 and 0.48% w/w. The use of complexes in emulsions with a low concentration of CH (<0.24% w/w) resulted in highly flocculated systems; instead, with increased level of CH, the emulsions had a smaller average droplet size and exhibited greater stability during storage. Emulsions stabilised by SSL/CH complexes showed non-Newtonian flow behavior with pronounced shear thinning. Among all formulations studied none showed a gel-like behavior since in all cases the G' (storage modulus) was lower that G'' (loss modulus). Adsorption kinetics of pure SSL and SSL/CH complexes to the oil/water interfaces were evaluated using an automated drop tensiometer (ADT). Even though complexation of SSL with CH resulted in a delay of the adsorption of the surface active species at the oil/water interface, the inclusion of the polysaccharide resulted in substantially improved interfacial properties as indicated by a significant increase of the dilatational modulus. Furthermore, the enhanced interfacial properties of the emulsion droplets resulted in improved stability against freeze thaw cycling. The results of this study may facilitate the development of frozen food products such as desserts with an ameliorated stability and favorable sensorial characteristics. PMID- 22298030 TI - A panel of five circulating microRNAs as potential biomarkers for prostate cancer. AB - BACKGROUND: Circulating microRNA (miRNAs) have been shown to have the potential as noninvasive diagnosis markers in several types of cancers. In this study, we investigated whether circulating miRNAs could be used in the diagnosis of prostate cancer (CaP) in a Chinese patient population. METHODS: Illumina's Human v2 miRNA microarray was used to analyze miRNAs levels in a small set of patients [25 CaP, 17 benign prostatic hyperplasia (BPH)] in an effort to identify CaP specific miRNAs. The identified miRNAs were further examined by quantitative real time PCR (qRT-PCR) in the same small set of patients. After the training phase of screening and selecting, the candidate miRNAs were validated in a larger independent cohort (80 CaP, 44 BPH, and 54 healthy controls) with qRT-PCR in the verification phase. RESULTS: Five miRNAs were confirmed by qRT-PCR analysis in validation sets. Receiver operating characteristic (ROC) curve analysis showed all 5 miRNAs had diagnostic value. More importantly, further principal component analysis indicated component 1 extracted from expression data of the 5 miRNAs could differentiate CaP from BPH and healthy controls with high diagnosis performance, with an AUC of 0.924 and 0.860, respectively. CONCLUSIONS: Our data suggested that circulating miRNAs could serve as biomarkers for CaP, and compared to single miRNA, the 5 miRNAs panel can accurately discriminate CaP from BPH and healthy controls with high sensitivity and specificity, and therefore, combined with routine PSA test, these 5 CaP-specific miRNAs may help improve CaP diagnosis in clinical application. PMID- 22298031 TI - Accumulation of unfavorable clinical and socioeconomic factors precludes living donor kidney transplantation. AB - BACKGROUND: In the past 30 years, the number of living donor kidney transplantations has increased considerably and nowadays outnumbers the deceased donor transplantations in our center. We investigated which socioeconomic and clinical factors influence who undergoes living or deceased donor kidney transplantation. METHODS: This retrospective study included all 1338 patients who received a kidney transplant between 2000 and 2011 in the Erasmus MC Rotterdam. Clinical and socioeconomic variables were combined in our study. Clinical variables were recipient age, gender, ethnicity, original disease, retransplants, ABO blood type, panel-reactive antibody, previous treatment, and transplantation year. Each recipient's postcode was linked to a postcode area information data base, to extract demographic information on urbanization level, percentage non Europeans in the area, income, and housing value. Chi-square, analysis of variance, and univariate and multivariate logistic regression analyses were performed. RESULTS: There were significant differences between the recipients of a living versus deceased donor kidney transplantation. In multivariate logistic regression analyses, 10 variables had a significant influence on the chance of receiving living donor kidney transplantation. Clinical and socioeconomic factors had an independent influence on this chance. Patients with ABO blood type O and B have smaller chances. Highly sensitized and elderly patients have smaller chances especially when combined with a collection of other unfavorable factors. Accumulation of unfavorable factors in non-Europeans prevents their participation in living donation programs. CONCLUSION: Both clinical and socioeconomic factors are associated with participation in living or deceased donor kidney transplantation. This study highlights the populations that would benefit from educational intervention regarding living donor transplantation. PMID- 22298032 TI - Hepatitis E virus and the kidney in solid-organ transplant patients. AB - BACKGROUND: Hepatitis E virus (HEV) infection is an emerging disease in industrialized countries. Few data regarding genotype 3 HEV extrahepatic manifestations exist. METHODS: We assessed kidney function and histology in solid organ transplant patients during HEV infection. In all, 51 cases of genotype 3 HEV infections were diagnosed (34 kidney, 14 liver, and 3 kidney-pancreas transplant patients). Of these, 43.2% were cleared of the virus spontaneously within 6 months of infection, whereas 56.8% evolved to chronic hepatitis. Twelve of these patients completed a 3-month antiviral therapy and were followed up for 6 months posttreatment. Kidney function (estimated glomerular filtration rate [eGFR] obtained by the Modification of Diet in Renal Disease equation) and proteinuria were assessed before infection, during HEV infection and during follow-up. Kidney biopsies were obtained from patients with high proteinuria and decreased eGFR levels. RESULTS: During HEV infection, there was a significant decrease in eGFR in both kidney- and liver-transplant patients. Glomerular diseases were observed in kidney biopsies obtained during the acute and chronic phases. This included membranoproliferative glomerulonephritis and relapses in IgA nephropathy. The majority of patients had cryoglobulinemia that became negative after HEV clearance. Kidney function improved and proteinuria decreased after HEV clearance. CONCLUSION: HEV-associated glomerulonephritis seems to be an HEV-related extrahepatic manifestation. Further studies are required to confirm these observations. PMID- 22298033 TI - Impact of conversion to a once daily tacrolimus-based regimen in kidney transplant recipients with gastrointestinal complications. AB - BACKGROUND: Gastrointestinal (GI) complications may affect up to 64% of kidney transplant recipients, with a higher incidence of symptoms in patients receiving tacrolimus-based immunosuppression. Tacrolimus extended release once-daily (OD) formulation offers the benefit of OD administration over standard tacrolimus, with a similar rate of GI complications when compared with the standard tacrolimus. We hypothesized that patients with tacrolimus-based immunosuppressive regimen with posttransplant gastrointestinal symptoms may benefit from a conversion to a tacrolimus OD regimen. METHODS: In this pilot study, 27 kidney transplant recipients with tacrolimus-related GI complications were converted to a tacrolimus OD regimen (group 1). This group was compared with a historical cohort of 30 patients on standard tacrolimus therapy with GI symptoms (group 2). Patients were followed up for 1 year after initial enrollment. RESULTS: Patients in group 1 reported a significant improvement in GI symptoms, as expressed by the change in the Gastrointestinal Symptom Rating Scale scores (1.7+/-0.3 vs. 1.2+/ 0.2, P<0.001) and GI-specific health-related quality of life scores (87+/-26.3 vs. 97+/-24.6, P<0.05). After comparing changes in Gastrointestinal Symptom Rating Scale total scores and subscale scores at 12 months, patients in Group 1 scored better than patients in Group 2 in total scores (-0.5 vs. -0.12, P<0.0001), abdominal pain (P<0.001), diarrhea (P<0.001), and reflux (P=0.013). CONCLUSIONS: Preliminary results from this study demonstrate that kidney transplant recipients experiencing tacrolimus-induced GI symptoms may benefit from a conversion to a tacrolimus OD regimen. PMID- 22298034 TI - Microtrauma-induced recurrent hyphema and secondary glaucoma associated with chronic acetylsalicylic acid use. AB - To report a case of microtrauma-induced recurrent hyphema and secondary glaucoma associated with voluntary chronic acetylsalicylic acid (ASA) use. A 43-year-old male developed advanced glaucoma in his right eye after a two-month followup period of recurrent microhyphema, which had been induced by strong eye-rubbing. In spite of topical and systemic antiglaucoma medication, as well as topical corticosteroid and cycloplegic drugs and bed rest under hospitalization, the hyphema and glaucoma were not controlled. His medical history revealed that he had been using ASA for 2 years in order to prevent heart attacks. We asked the patient to stop ASA intake and the hyphema cleared considerably on the third day after discontinuation of the drug. One week after stopping ASA, trabeculectomy with mitomycin C was performed without any complications. Glaucoma and recurrent hyphema were controlled after surgery without any medical treatment. Chronic ASA intake may cause recurrent hyphema and secondary glaucoma even after a microtrauma. Medical histories of patients must always be taken, especially in cases of prolonged recurrent hyphema. PMID- 22298035 TI - Influence of temperature and interactions with ligands on dissociation of dsDNA and ligand-dsDNA complexes of various types of binding. An electrochemical study. AB - Several medicinally important compounds that bind to dsDNA strands via intercalation (C-1311, C-1305, EtBr), major groove binding (Hoechst 33258) and covalent binding (cis-Pt) were examined. The obtained results suggest that both the transfer of conformation B to C and the denaturation process, for the ligand dsDNA complexes, except for covalently bound cis-Pt, took place at higher temperatures compared to the unbound helix. Furthermore, much lower currents of electrooxidation of guanine at 100 degrees C, compared to the currents obtained at this temperature for dsDNA in the absence of ligands, suggest that the binding of ligands affects the way the dsDNA denaturates at increased temperatures and leads to formation of different forms of DNA single strands. The voltammetric results were compared with the data of two spectroscopic techniques: UV-Vis and CD. PMID- 22298036 TI - The inflow of sensory information for the control of standing is graded and bidirectional. AB - The control of upright standing is accomplished through the integration of different sources of sensory information and by providing an appropriate motor program to control both expected and unexpected perturbations imposed on the system. However, the dynamic characteristics of postural sway and its interplay with the regulation of Ia sensory information within the spinal cord are largely unknown. Here, using a stochastic technique for analyzing the dynamics of upright standing, we demonstrate that the changes in the dynamics of postural sway were accompanied by modulation of the soleus H-reflex during quiet standing. While the causality of this relation was not established, the results showed that these changes were independent of the sway of the center of pressure and were bidirectional and purposeful. With this novel perspective, the appropriate reflex gain, which is important for balance control, can be predicted from the dynamic characteristics of postural sway. Our current findings provide the first human behavioral evidence to suggest the contribution of the spinal cord in fulfilling the desired motor programming of a complex task. This contribution is, by conventional guess, carried out through interneuronal adjustments, which are under the control of different brain areas. PMID- 22298037 TI - On target: a public repository for large-scale RNAi experiments. PMID- 22298038 TI - Finding MyoD with a little help from my friends. PMID- 22298039 TI - Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system. AB - The ATP-driven chaperone valosin-containing protein (VCP)/p97 governs critical steps in ubiquitin-dependent protein quality control and intracellular signalling pathways. It cooperates with diverse partner proteins to help process ubiquitin labelled proteins for recycling or degradation by the proteasome in many cellular contexts. Recent studies have uncovered unexpected cellular functions for p97 in autophagy, endosomal sorting and regulating protein degradation at the outer mitochondrial membrane, and elucidated a role for p97 in key chromatin-associated processes. These findings extend the functional relevance of p97 to lysosomal degradation and reveal a surprising dual role in protecting cells from protein stress and ensuring genome stability during proliferation. PMID- 22298040 TI - Stromal miR-320 keeps an oncogenic secretome in check. PMID- 22298041 TI - Efficient generation of adipocytes in a dish. PMID- 22298042 TI - Ras hitchhikes on PDE6delta. PMID- 22298049 TI - Spectrum of urodynamic abnormalities and renal function changes in adult men with non-neurogenic urinary retention. AB - INTRODUCTION: The purpose of this study was to identify abnormalities in bladder and renal function in men with urinary retention presumed to be due to BPH. METHODS: In this retrospective analysis, urodynamic studies (UDS) and renal function were evaluated. Bladder contractility and compliance and the severity of bladder outlet obstruction (BOO) were determined from urodynamics. Renal function (BUN, creatine, eGFR) was assessed prior to retention, at the time of presentation and after urodynamic evaluation. RESULTS: Of 87 patients with evaluable UDS, 48% did not demonstrate detrusor activity during testing while 52% showed some detrusor contractile activity. Of these, 23% did not have BOO. Diminished bladder compliance was detected in 56%. In the entire cohort, BUN, serum creatinine, and eGFR were significantly changed during retention but were restored after catheterization. In older patients (>75 years), BUN and creatinine during retention were significantly higher, and eGFR was significantly lower compared to younger patients, but renal function after catheterization was not different between age groups. No significant correlations were found between renal function measurements and bladder compliance or age. CONCLUSION: The urodynamic spectrum in men with urinary retention ranged from detrusor acontractility to varied degrees of contractility associated with outlet obstruction spanning from equivocal to severe. Moreover, prompt relief of retention restores renal function to baseline levels, regardless of age. This study indicates that prostatic obstruction may not be the only cause of urinary retention in adult men presumed to have BPH and illustrates the value of urodynamic assessment prior to potentially failure-prone surgical interventions. PMID- 22298050 TI - Isolation and identification of spermidine derivatives in tea (Camellia sinensis) flowers and their distribution in floral organs. AB - BACKGROUND: Recently, tea (Camellia sinensis) flowers have attracted increasing interest because of their content of bioactive compounds such as catechins. The aim of this study was to investigate the occurrence of some characteristic compounds in tea flowers. RESULTS: A principal component analysis of metabolites using ultra-performance liquid chromatography/time-of-flight mass spectrometry showed differences in metabolite profile between flowers and leaves of C. sinensis var. Yabukita. Four spermidine derivatives were isolated from tea flowers. One of them was determined as N(1) ,N(5) ,N(10) -tricoumaroyl spermidine based on NMR, MS and UV data. The other three were identified as feruoyl dicoumaroyl spermidine, coumaroyl diferuoyl spermidine and triferuoyl spermidine based on MS(n) data. Tricoumaroyl spermidine as the major spermidine conjugate was not detected in tea leaves. Furthermore, it decreased during floral development and mainly occurred in anthers. CONCLUSION: This study has provided the first evidence that spermidine-phenolic acid conjugates occur in tea flowers in considerable amounts. Their presence should prompt a reconsideration of the ecological role of tea flowers. From an economic point of view, tea flowers might be suitable as a raw material in the healthcare food and pharmaceutical industries. PMID- 22298051 TI - The dramatic increase in total knee replacement utilization rates in the United States cannot be fully explained by growth in population size and the obesity epidemic. AB - BACKGROUND: Total knee replacement utilization in the United States more than doubled from 1999 to 2008. Although the reasons for this increase have not been examined rigorously, some have attributed the increase to population growth and the obesity epidemic. Our goal was to investigate whether the rapid increase in total knee replacement use over the past decade can be sufficiently attributed to changes in these two factors. METHODS: We used data from the Nationwide Inpatient Sample to estimate changes in total knee replacement utilization rates from 1999 to 2008, stratified by age (eighteen to forty-four years, forty-five to sixty four years, and sixty-five years or older). We obtained data on obesity prevalence and U.S. population growth from federal sources. We compared the rate of change in total knee replacement utilization with the rates of population growth and change in obesity prevalence from 1999 to 2008. RESULTS: In 2008, 615,050 total knee replacements were performed in the United States adult population, 134% more than in 1999. During the same time period, the overall population size increased by 11%. While the population of forty-five to sixty four-year-olds grew by 29%, the number of total knee replacements in this age group more than tripled. The number of obese and non-obese individuals in the United States increased by 23% and 4%, respectively. Assuming unchanged indications for total knee replacement among obese and non-obese individuals with knee osteoarthritis over the last decade, these changes fail to account for the 134% growth in total knee replacement use. CONCLUSIONS: Population growth and obesity cannot fully explain the rapid expansion of total knee replacements in the last decade, suggesting that other factors must also be involved. The disproportionate increase in total knee replacements among younger patients may be a result of a growing number of knee injuries and expanding indications for the procedure. PMID- 22298052 TI - Effects of cast-mediated immobilization on bone mineral mass at various sites in adolescents with lower-extremity fracture. AB - BACKGROUND: Leg or ankle fractures occur commonly in the pediatric population and are primarily treated with closed reduction and cast immobilization. The most predictable consequences of immobilization and subsequent weight-bearing restriction are loss of bone mineral mass, substantial muscle atrophy, and functional limitations. The purposes of this study were to determine if lower limb fractures in adolescents are associated with abnormal bone mineral density or content at the time of fracture, and to quantify bone mineral loss at various sites due to cast-mediated immobilization and limited weight-bearing. METHODS: We recruited fifty adolescents aged ten to sixteen years who had undergone cast immobilization for a leg or ankle fracture. Dual x-ray absorptiometry scans of the total body, lumbar spine, hip, leg, and calcaneus were performed at the time of fracture and at cast removal. Patients with a fracture were paired with healthy controls according to sex and age. Values at baseline and at cast removal, or at equivalent time intervals in the control group, were compared between groups and between the injured and uninjured legs of the adolescents with the fracture. RESULTS: At the time of fracture, there were no observed differences in the bone mineral density or bone mineral content Z-scores of the total body or the lumbar spine, or in the bone mineral density Z-scores of the calcaneus, between the injured and healthy subjects. At cast removal, bone mineral parameters on the injured side were significantly lower than those on the uninjured side in the injured group. Differences ranged from -5.8% to -31.7% for bone mineral density and from -5.2% to -19.4% for bone mineral content. During the cast period, the injured adolescents had a significant decrease of bone mineral density at the hip, greater trochanter, calcaneus, and total lower limb as compared with the healthy controls. CONCLUSIONS: Lower-limb fractures are not related to osteopenia in adolescents at the time of fracture. However, osteopenia does develop in the injured limb during cast immobilization for fracture treatment. Further investigation is required to determine if the bone mineral mass will return to normal or if a permanent decrease is to be expected, which may constitute a hypothetical risk of sustaining a second fracture. PMID- 22298053 TI - An association of lateral knee sagittal anatomic factors with non-contact ACL injury: sex or geometry? AB - BACKGROUND: Lateral tibiofemoral articular geometry may play a role in the development of non-contact anterior cruciate ligament (ACL) injuries. We hypothesized that athletes who had sustained an ACL injury would demonstrate more highly convex articular surfaces in the lateral compartment of the knee compared with activity-matched athletes who had not sustained an ACL injury, and that women would demonstrate greater absolute and relative convexity of these articular surfaces than men. METHODS: One hundred and twelve athletes with a non contact ACL injury and sixty-one activity-matched athletes without an ACL injury were studied. Three blinded observers measured the articular geometry in the mid lateral sagittal plane with use of magnetic resonance imaging. The tibial plateau radius of curvature (TPr), distal femoral radius of curvature (Fr), maximal femoral anteroposterior articular length (FAP), and maximal tibial anteroposterior articular length (TPAP) were recorded. The Fr:TPr and FAP:TPAP ratios were also calculated to adjust for size variations. The intraclass correlation coefficient and the two-sample Student t test were used to compare quantitative variables. All data were found to follow a normal distribution. RESULTS: When data for male and female patients were combined, the mean TPr, Fr, and TPAP values were significantly smaller in the ACL-injured patients than in the uninjured patients (33.9 compared with 37.5 mm, p = 0.005; 24.3 compared with 25.1 mm, p = 0.04; and 31.5 compared with 33.1 mm, p = 0.007; respectively). The mean FAP value did not differ significantly between the ACL-injured and uninjured patients but the difference in the mean FAP:TPAP value was significant (p = 0.003). When only male patients were analyzed, the mean TPr, Fr, and TPAP values were also significantly smaller in the ACL-injured patients than in the uninjured patients (35.5 compared with 41.1 mm, p = 0.002; 25.5 compared with 26.7 mm, p = 0.001; and 33.0 compared with 35.5 mm, p = 0.0002; respectively). The mean FAP value did not differ significantly between the ACL-injured and uninjured male patients, but the difference in the mean FAP:TPAP value was significant (p = 0.0005). In contrast, when only female patients were analyzed, none of the mean values differed significantly between the ACL-injured and uninjured patients. The FAP:TPAP and Fr:TPr values did not differ significantly among the ACL-injured male patients, injured female patients, and uninjured female patients. CONCLUSIONS: All female patients (both ACL-injured and uninjured) and ACL-injured male patients shared a common lateral knee geometry characterized by a smaller tibial plateau length relative to the femur and by more convex articulating surfaces of the proximal aspect of the tibia and the distal aspect of the femur. Shorter, more highly convex articulating surfaces may be inherently less stable with regard to anterior tibial translation and rotation. These findings may partially explain the greater overall predisposition of women compared with men toward ACL injury as well as why some studies have demonstrated no sex differences in graft reinjury after ACL reconstruction. PMID- 22298054 TI - National trends in rotator cuff repair. AB - BACKGROUND: Recent publications suggest that arthroscopic and open rotator cuff repairs have had comparable clinical results, although each technique has distinct advantages and disadvantages. National hospital and ambulatory surgery databases were reviewed to identify practice patterns for rotator cuff repair. METHODS: The rates of medical visits for rotator cuff pathology, and the rates of open and arthroscopic rotator cuff repair, were examined for the years 1996 and 2006 in the United States. The national incidence of rotator cuff repairs and related data were obtained from inpatient (National Hospital Discharge Survey, NHDS) and ambulatory surgery (National Survey of Ambulatory Surgery, NSAS) databases. These databases were queried with use of International Classification of Diseases, Ninth Revision (ICD-9) procedure codes for arthroscopic (ICD-9 codes 83.63 and 80.21) and open (code 83.63 without code 80.21) rotator cuff repair. We also examined where the surgery was performed (inpatient versus ambulatory surgery center) and characteristics of the patients, including age, sex, and comorbidities. RESULTS: The unadjusted volume of all rotator cuff repairs increased 141% in the decade from 1996 to 2006. The unadjusted number of arthroscopic procedures increased by 600% while open repairs increased by only 34% during this time interval. There was a significant shift from inpatient to outpatient surgery (p < 0.001). CONCLUSIONS: The increase in national rates of rotator cuff repair over the last decade has been dramatic, particularly for arthroscopic assisted repair. PMID- 22298055 TI - Primary cementless acetabular fixation at a minimum of twenty years of follow-up: a concise update of a previous report. AB - The purpose of the present study was to analyze the longer-term results for a previously reported cohort of patients with cementless acetabular fixation and to compare the results with those for historical controls with cement fixation and a comparable follow-up period. One hundred and twenty consecutive nonselected total hip arthroplasties were performed in 108 patients with use of a cementless acetabular component. This series was evaluated at a minimum of twenty years of follow-up and was compared with 330 consecutive hip arthroplasties that had been performed by the same surgeon with use of cemented acetabular components and had been followed for a comparable period of time. Thirty-nine patients (forty-two hips) in the cementless fixation group were living at twenty years of follow-up. In the group of 120 hips with cementless acetabular fixation, twenty-two hips (18.3%) were revised during the follow-up period, but only one hip (0.8%) was revised because of loosening of the acetabular component, with no additional cup loosening since the previous report at thirteen to fifteen years of follow-up. In the group with cemented acetabular fixation with comparable follow-up, thirty-two hips (10%) were revised overall and eighteen hips (6%) were revised because of acetabular loosening. An additional twenty-five hips (8%) had acetabular cups that were loose on radiographs but had not undergone revision. At a minimum of twenty years of follow-up, cementless acetabular components provided superior long-term fixation compared with cemented components but the overall rates of acetabular revision for mechanical reasons were comparable. PMID- 22298056 TI - Incidence of elbow dislocations in the United States population. AB - BACKGROUND: There is minimal published information regarding the epidemiology of simple elbow dislocations. The purpose of this study was to report the estimated incidence of elbow dislocations in the United States, with use of the National Electronic Injury Surveillance System (NEISS) database. METHODS: The NEISS database includes 102 hospitals representing a random sampling of all patients presenting to U.S. emergency departments. The database was queried for elbow dislocation events. NEISS data for 2002 through 2006 were used for raw data and weighted injury counts. Incidence rates with 95% confidence intervals (95% CI) were calculated by age group and sex, with use of U.S. census data. RESULTS: One thousand and sixty-six elbow dislocations were identified, representing a weighted estimate of 36,751 acute dislocations nationwide. A calculated incidence of 5.21 dislocations per 100,000 person-years (95% CI, 4.74 to 5.68) was noted. The highest incidence of elbow dislocations (43.5%) occurred in those who were ten to nineteen years old (6.87 per 100,000 person-years; 95% CI, 5.97 to 7.76). The incidence rate ratio for the comparison of dislocations in males with those in females was 1.02 (5.26 per 100,000 for males and 5.16 per 100,000 for females). In patients ten years or older, 474 injuries (44.5% of total dislocations) were sustained in sports. Males dislocated elbows in football, wrestling, and basketball. Females sustained elbow dislocations most frequently in gymnastics and skating activities. CONCLUSIONS: The estimated incidence of elbow dislocations in the U.S. population is 5.21 per 100,000 person-years, with use of a national database. Adolescent males are at highest risk for dislocation. Nearly half of acute elbow dislocations occurred in sports, with males at highest risk with football, and females at risk with gymnastics and skating activities. PMID- 22298057 TI - Closed treatment of overriding distal radial fractures without reduction in children. AB - BACKGROUND: Traditionally, distal radial fractures with marked displacement and angulation have been treated with closed or open reduction techniques. Reduction maneuvers generally require analgesia and sedation, which increase hospital time, cost, patient risk, and the surgeon's time. In our study, a treatment protocol for pediatric distal radial fractures was used in which the fracture was left shortened in an overriding position and a cast was applied without an attempt at anatomic fracture reduction. METHODS: Consecutive patients three to ten years of age presenting between 2004 and 2009 with a closed overriding fracture of the distal radial metaphysis were followed prospectively. Our protocol consisted of no analgesia, no sedation, and a short arm fiberglass cast gently molded to correct only angulation. Patients were followed for at least one year. All parents or guardians were given a questionnaire assessing their satisfaction with the treatment. Financial analysis was performed with use of Current Procedural Terminology codes and the average total cost of care. RESULTS: Fifty-one children with an average age of 6.9 years were included in the study. Initial radial shortening averaged 5.0 mm. Initial sagittal and coronal angulation averaged 4.0 degrees and 3.2 degrees , respectively. The average duration of casting was forty-two days. Residual sagittal and coronal angulation at the time of final follow-up averaged 2.2 degrees and 0.8 degrees , respectively. All fifty-one patients achieved clinical and radiographic union with a full range of wrist motion. All parents and guardians answered the questionnaire and were satisfied with the treatment. Cost analysis demonstrated that closed reduction with the patient under conscious sedation or general anesthesia is nearly five to six times more expensive than the treatment used in this study. Adding percutaneous pin fixation increases costs nearly ninefold. CONCLUSIONS: This treatment protocol presents an alternative approach to overriding distal radial fractures in children and provides the orthopaedic surgeon a simple, effective, and cost and time-efficient method of treatment. PMID- 22298058 TI - The influence of posterolateral rotatory instability on ACL reconstruction: comparison between isolated ACL reconstruction and ACL reconstruction combined with posterolateral corner reconstruction. AB - BACKGROUND: The purpose of the present retrospective study was to evaluate the influence of posterolateral corner reconstruction on anterior cruciate ligament (ACL) reconstruction in terms of anterior laxity and clinical outcomes. We hypothesized that the effects of combined ACL and posterolateral corner reconstruction would be less satisfactory than those of isolated ACL reconstruction in terms of anterior laxity and clinical outcomes. METHODS: We retrospectively studied sixty-nine patients who underwent ACL reconstruction from February 2001 to December 2005. Forty-six patients underwent isolated ACL reconstruction (Group I), and twenty-three patients underwent combined ACL and posterolateral corner reconstruction (Group II). Clinical outcomes were determined from data obtained before surgery and at the time of the twenty-four month follow-up examination. RESULTS: Postoperatively, the mean side-to-side difference (and standard deviation) in anterior tibial translation, measured with a KT2000 arthrometer, was greater for Group I (2.2 +/- 1.0 mm) than for Group II (1.6 +/- 0.8 mm) (p = 0.031). Seven knees (15.2%) in Group I and two knees (8.7%) in Group II had grade-1 anterior translation. The mean Lysholm score was 93.2 in Group I and 90.1 in Group II (p = 0.392). Thirty-eight knees (82.6%) in Group I and twenty knees (87.0%) in Group II were classified as normal or nearly normal according to the International Knee Documentation Committee scoring system (p = 0.882). CONCLUSIONS: On the basis of the evaluation of ligamentous laxity with use of the KT2000 arthrometer, we observed that combined ACL and posterolateral corner reconstruction allows less anterior translation than isolated ACL reconstruction. However, we could not identify significant differences between the two groups in terms of functional outcomes. PMID- 22298059 TI - Total shoulder arthroplasty with an all-polyethylene pegged bone-ingrowth glenoid component: a clinical and radiographic outcome study. AB - BACKGROUND: Loosening of the glenoid component continues to be the foremost cause of medium and long-term failure of shoulder replacements. The purpose of this study was to evaluate the clinical and radiographic results of a minimally cemented all-polyethylene pegged glenoid component designed for biologic fixation. METHODS: Forty-four shoulders in forty-one patients with a mean age of sixty-six years underwent total shoulder arthroplasty with a pegged bone-ingrowth glenoid component. Outcome data included the American Shoulder and Elbow Surgeons questionnaire, the Simple Shoulder Test, and visual analog scales. A detailed radiographic analysis was performed by two board-certified musculoskeletal radiologists who were blinded to clinical and patient-reported outcomes. The radiographs were evaluated with regard to the presence of radiolucent lines at the bone-cement interface, implant seating, and the radiodensity between the flanges of the central peg. RESULTS: The mean duration of clinical follow-up was four years and the mean duration of radiographic follow-up was three years. Twenty shoulders had perfect seating and radiolucency grades, thirty had increased radiodensity between the flanges of the central peg, and three demonstrated osteolysis. Radiodensity about the uncemented central peg at the time of the latest follow-up was positively associated with perfect seating and radiolucency grades on the initial postoperative radiographs (p = 0.03, Fisher exact test). The Simple Shoulder Test score, the American Shoulder and Elbow Surgeons score, and all visual analog scale scores had improved significantly (p < 0.01) at the time of the latest follow-up. CONCLUSIONS: Total shoulder arthroplasty with a minimally cemented, all-polyethylene, pegged glenoid implant can yield stable and durable fixation at short to medium-term follow-up (mean, four years). PMID- 22298060 TI - Anatomic landmarks utilized for physeal-sparing, anatomic anterior cruciate ligament reconstruction: an MRI-based study. AB - BACKGROUND: Anterior cruciate ligament (ACL) injury and reconstruction in the skeletally immature patient are becoming more common. The purpose of this study was to develop a reproducible anatomic ACL reconstruction technique, based on intra-articular and extra-articular landmarks, that reliably produces a femoral tunnel of adequate length and diameter while avoiding the distal femoral physis. METHODS: Magnetic resonance images (MRIs) of one hundred and eighty-eight children (age range, six to seventeen years) were evaluated. Two extra-articular landmarks, the femoral insertion of the popliteus tendon and the lateral femoral epicondyle, and one intra-articular landmark, the central portion of the femoral footprint of the ACL, were identified. Computer software was used to plot these landmarks in all three planes and to draw lines representing two potential femoral tunnels. The first line connected the center of the ACL femoral footprint with the insertion of the popliteus tendon, and the second connected the center of the ACL femoral footprint with the lateral femoral epicondyle. The length of each tunnel, the shortest distance from the center of each tunnel to the distal femoral physis, and the height of the lateral femoral condyle from the physis to the chondral surface and to the base of the cartilage cap were calculated. A three-dimensional MRI reconstruction was used to confirm that placement of a femoral tunnel with use of the chosen landmarks would avoid the distal femoral physis. RESULTS: The mean distance from the center of the preferred ACL tunnel, which connected the center of the ACL femoral footprint with the insertion of the popliteus tendon, to the distal femoral physis was 12 mm, independent of sex (p = 0.94) or age, and the shortest distance was 8 mm. The length of this proposed tunnel averaged 30.1 mm in the boys and 27.4 mm in the girls (p < 0.001), and it averaged 25.4 mm at an age of six years and 29.7 mm at an age of seventeen years. The mean distance from the center of the alternative tunnel, which connected the center of the ACL femoral footprint with the lateral epicondyle, to the distal femoral physis was 8.8 mm in the boys and 8.9 mm in the girls (p = 0.55). The mean length of this alternative tunnel was 34.3 mm in the boys and 31.6 mm in the girls (p < 0.001). CONCLUSIONS: Drilling from the center of the ACL femoral footprint to the insertion of the popliteus tendon would have resulted in a mean tunnel length of 27 to 30 mm, and it would have allowed the safe placement of a femoral tunnel at least 7 mm in diameter in a patient six to seventeen years old. The center of the ACL femoral footprint and the popliteus insertion are easily identifiable landmarks and will allow safe, reproducible, anatomic ACL reconstruction in the skeletally immature patient. PMID- 22298061 TI - Upper extremity-specific measures of disability and outcomes in orthopaedic surgery. AB - Outcome measures may consist of simple questions or they may be more complex instruments that evaluate multiple interrelated domains that influence patient function. Outcome measures should be relevant to patients, easy to use, reliable, valid, and responsive to clinical changes. The Disabilities of the Arm, Shoulder and Hand score can be used to measure disability for any region of the upper limb. Joint and disease-specific outcome measures have been developed for the shoulder, the elbow, and the wrist and hand. Many of these measures would benefit from further research into their validity, reliability, and optimal applicability. PMID- 22298062 TI - Intrathoracic displacement of a scapular fracture: a case report. PMID- 22298063 TI - Chondrogenic potential and homogeneity of cell populations of donor and recipient cells in a fresh osteochondral allograft: a case report. PMID- 22298064 TI - The prevalence of defensive orthopaedic imaging: a prospective practice audit in Pennsylvania. AB - BACKGROUND: Defensive medicine has been identified as an area of wasteful health care spending. Estimates of its prevalence and its contribution to the cost of defensive practices have varied widely. To date, there has been no prospective evaluation of the use of defensive medicine for musculoskeletal conditions. METHODS: Members of the Pennsylvania Orthopaedic Society were queried by means of an anonymous, prospective audit of consecutive imaging decisions in their clinical practice. For each image order, respondents recorded the modality, the body region imaged, and whether the imaging was "required for clinical care" or "ordered for defensive reasons." We evaluated the proportion of images that were ordered defensively, identified demographic differences with use of the chi square test of independence, and calculated the contribution of defensive imaging to the total cost with use of 2009 Medicare reimbursement rates. RESULTS: Seventy two orthopaedists recorded 2068 imaging decisions made during the day that their practice was audited. Defensive imaging represented 19.1% (396) of the orders and 34.7% ($113,675) of the total cost ($327,414). Magnetic resonance imaging (MRI) represented 48.7% of the defensive orders, and 38.5% (193) of the 501 MRIs were ordered for defensive reasons. The proportion of defensive imaging ordered by orthopaedists who had been sued for medical malpractice within the previous five years was significantly greater than the proportion ordered by those who had not been sued during the same time frame (24.6% compared with 15.1%, p < 0.001). The proportion of defensive imaging ordered by orthopaedists who had been in practice for more than fifteen years was significantly greater than the proportion ordered by those who had less experience (20.8% compared with 17.1%, p = 0.03). CONCLUSIONS: In a prospective practice audit of orthopaedists, defensive imaging was found to be both common and costly. Recent litigation experiences and longer duration of orthopaedic practice were independent predictors of an increased use of defensive practices in ordering imaging studies. This real-time audit showed that a large proportion of MRI studies were ordered for primarily defensive medicine reasons. PMID- 22298065 TI - Bone mineral density after immobilization for fractures in adolescents: commentary on an article by Dimitri Ceroni, MD, et al.: "Effects of cast-mediated immobilization on bone mineral mass at various sites in adolescents with lower extremity fracture". PMID- 22298066 TI - Non-contact ACL injury: can anatomic factors be used in screening at-risk athletes? Commentary on an article by Christopher J. Wahl, MD, et al.: "An association of lateral knee sagittal anatomic factors with non-contact ACL injury: sex or geometry?". PMID- 22298067 TI - Colonic mucosal bridging in ulcerative colitis. PMID- 22298068 TI - The pressure induced insulator to metal transition in FeSb2. AB - The evolution of the ground state properties of FeSb(2) has been investigated via temperature (4.2-300 K), magnetic field (0-12 T) and pressure (0-8.8 GPa) dependent electrical resistivity studies. The temperature dependence of the resistivity follows activated behavior in the high temperature (HT) regime (T > 60 K), while variable range hopping (VRH) dictates the transport in the intermediate temperature (IT) regime (10 K > T > 45 K) and power law behavior is observed in the low temperature (LT) regime (T < 10 K). The pressure profoundly affects the resistivity in all the temperature regimes. The energy gap (Delta) extracted in the HT regime initially increases with pressure and then decreases, while the VRH parameter T(0) deduced in the IT regime is seen to decrease monotonically and vanish beyond 5 GPa leading to an insulator to metal transition (MIT) on account of delocalization of the electronic states in the gap. The analysis of the logarithmic derivative of the conductivity indicates the MIT to occur at ~6 GPa. The magnetoresistivity is found to be positive. The analysis of the resistivity behavior under pressure and magnetic field indicates that the former induces delocalization, while the latter tends to assist localization of the defect states inside the gap of FeSb(2). PMID- 22298069 TI - [Recent progress in the treatment of rheumatoid arthritis]. AB - Rheumatoid arthritis (RA) is a representative autoimmune disease characterized by chronic and destructive inflammatory synovitis that causes severe disability and mortality. Since joint destruction occurs from the early disease, its diagnosis and treatment have to be done timely. 2010 RA classification criteria redefine the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease. Thus, a new concept of 'treat-to-target' is emerging in treatments of RA, whereby patients are treated according to prespecified goals, such as remission. Accordingly, the combinational use of methotrexate and biologics targeting TNF and IL-6 has revolutionized the treatment of RA, producing significant improvements in clinical and structural outcomes, and has produced upcoming endpoint for the treatment as the clinical and structural remission. PMID- 22298070 TI - [Bone and cartilage destruction in rheumatoid arthritis]. AB - Rheumatoid arthritis is an inflammation-mediated bone disease characterized by local joint inflammation which results from systemic immune responses. It is essential to clarify the mechanisms by which inflammation elicits bone destruction for the establishment of novel therapeutic strategies. Advances in osteoimmunology, in addition to the development of a various kind of genetically modified mice and animal models of RA, have greatly contributed to our understanding of these mechanisms. Recently, Th17 cells have been shown to contribute not only to the initiation and amplification of inflammation in RA, but also to bone destruction by enhancing osteoclast differentiation through the interaction with synovial fibroblasts. Thus, Th17-synovial fibroblasts interaction is considered to be a promising therapeutic target for RA. PMID- 22298071 TI - [Musculoskeletal ultrasonography in rheumatoid arthritis]. AB - Musculoskeletal ultrasonography has spread rapidly in the field of rheumatology. Ultrasonography is able to accurately evaluate synovial lesion, and it detect bone lesion in the patients with rheumatoid arthritis (RA) in early stage. Power Doppler signals with synovial hypertrophy mean disease activity of RA. Therefore, ultrasonography is very useful in not only the early diagnosis but also the evaluation of disease activity as well as evaluation of treatment choice in the patients with RA. Additionally, it improves the technique of physical examination and assists the patient education. Musculoskeletal ultrasonography suggested to be generalized in the rheumatologic practice in Japan. PMID- 22298072 TI - [Evaluation of joint inflammation by MRI in patients with RA]. AB - We compared the characteristics of MRI imaging and US imaging on joint inflammation in patients with rheumatoid arthritis (RA) . MRI imaging is worth for diagnosis of RA at the early stage, evaluation of drug treatment effects, and a new measure for true remission. US imaging is also useful for estimation of therapy and a criteria for complete remission, and cheep machine. We hope that both imaging technologies will be a standard for diagnosis and therapy evaluation in RA patients. PMID- 22298073 TI - [Biomarker of bone destruction]. AB - Patients with rheumatoid arthritis (RA) often have progression of bone destruction owing to chronic inflammation. Treatment for bone destruction is still insufficient in these patients although goal of treatment has become remission since biologics have been used widely. It is shown that collagen cross linked C-peptide (CTX- I ) and tartrate-resistant acid phosphatase (TRACP) have correlated with bone destruction in patients with RA, in addition, evidence of new biomarker such as hepatocyte growth factor and macrophage inhibitory factor have been accumulated recently. These biomarkers may help evaluation of bone quality clinically. PMID- 22298074 TI - [Clinical significance of serum cartilage biomarkers in the treatment of rheumatoid arthritis with biological therapy]. AB - With the current use of biologics in RA, numerous patients can achieve clinical remission, however structural joint damage occurs in substantial numbers of the patients. The present study assessed cartilage damage during 54-week anti-TNF therapy, using serum cartilage markers, and potential advantages of these markers were evaluated. Levels of serum hyaluronan decreased with decreasing levels of CRP in both early and established RA, whereas indicator of type II collagen synthesis/degradation, C2C/CP II decreased only in early RA group. Levels of COMP and keratin sulfate significantly decreased and increased compared to baseline, respectively, by week 54 in established RA. Strikingly, C2C/CP II levels were universally improved in early RA, regardless of CRP levels or EULAR response grade. In contrast, C2C/CP II levels universally worsened in established RA, even though patients achieved good response. As a role of surrogate marker reflecting therapeutic efficacy of biological therapy, C2C/CP II appears particularly useful for determining the degree of ongoing structural joint deterioration, which is dissociated from clinical assessment of disease activity in RA. PMID- 22298075 TI - [ Bone and cartilage destruction in RA and its intervention. Disease-modifying antirheumatic drugs]. AB - The primary goal in the treatment of rheumatoid arthritis (RA) is to maintain good quality of life by preventing joint destruction and avoiding disability. For this purpose, all patients with the diagnosis of RA should be treated by disease modifying antirheumatic drugs (DMARDs) including biologic DMARDs and non-biologic DMARDs. All DMARDs are expected to prevent the progression of bone and cartilage destruction of RA patients from the results of in vitro research, and prevention of joint destruction is confirmed in vivo in all biologic DMARDs, but not in all non-biologic DMARDs. In this chapter, we would like to review the results of basic researches and clinical studies to demonstrate the prevention of joint destruction by non-biologic DMARDs that have been frequently used I daily practice. PMID- 22298076 TI - [Bone and cartilage destruction in RA and its intervention. Biological agents]. AB - The combination therapy of biological agents such as anti-tumor necrosis factor monoclonal antibody and methotrexate resulted in the arrest of joint destruction in most of the patients with rheumatoid arthritis, and even repair of damaged joints in some patients. The fact that the combination therapy leads to less joint destruction than methotrexate monotherapy in patients with comparable disease activity indicates the beneficial effects of biological agents for patients without remission state. Furthermore, the RISING study revealed the importance of sufficient dosing of biological agents such as infliximab because of the different requirement for the dosage of biological agents among patients with rheumatoid arthritis. PMID- 22298077 TI - [Glucocorticoid-induced osteoporosis : treatment update]. AB - Glucocorticoid-induced osteoporosis is one of the most important side effects of glucocorticoid use, as it leads to an increased risk of fracture. The skeletal effects of glucocorticoids include both direct and indirect actions on bone that result in an early, transient increase in bone resorption accompanied by a decrease in bone formation, which is maintained for the duration of glucocorticoid therapy. Rapid bone loss and increase fracture risk occur soon after the initiation of glucocorticoid therapy and dose dependent. The increase in fracture risk is partly independent of bone mineral density, probably as a result of changes in bone material properties and an increased risk of falling. Bisphosphonates are the front-line choice for prevention of fracture in glucocorticoid-treated patients, with teriparatide as the second-line option ; calcium and vitamin D supplements should be co-prescribed in the majority of individuals. Fracture risk can be assessed using the FRAX((r)) algorithm, although risk may be underestimated in patients taking higher doses of glucocorticoids. PMID- 22298078 TI - [Replacement arthroplasty for patients with rheumatoid arthritis]. AB - Replacement arthroplasty is an excellent method to improve activities of daily living (ADL) and quality of life (QOL) in patients with rheumatoid arthritis (RA) . In many cases of RA, prosthetic surgery is carried out on multiple joints. When prosthetic surgery is performed in cases with severe knee contracture or joint destruction, surgical invasion can be extensive. Regarding timing of surgery, it is better while the joint is still somewhat intact, and as long as the operability conditions can be met, age is irrelevant. It is important not to delay the timing of surgery. This article mainly considers total knee arthroplasty (TKA). PMID- 22298079 TI - [Cartilage implantation for the bone and cartilage destruction in rheumatoid arthritis]. AB - Current pharmacological treatment of rheumatoid arthritis developed to increase the chance for reaching complete remission. However, it is unclear that it could help regeneration or repair of the destroyed cartilage. One of the most prominent candidates for the treatment of destroyed cartilage in rheumatoid arthritis after complete remission is the mesenchymal stem cells. PMID- 22298080 TI - [Which questionnaire is suitable for the QOL evaluation of osteoporotic patiemts? JOQOL is osteoporosis-targeted]. AB - JOQOL (Japanese Osteoporosis quality of life questionnaire) is osteoporosis targeted QOL to evaluate QOL of osteoporotic cases.The total scores of JOQOL is related to the number spinal fractures. Furthermore, the patients with spinal kyphosis showed lower QOL scores compared to non-kyphotic cases. JOQOL is useful tool to evaluate the QOL status in osteoporotis cases. PMID- 22298081 TI - [SF-36 and EQ-5D in the evaluation of QOL in the osteoporotic patients as the generic questionnaires]. AB - Health-related quality of life (HRQOL) , abbreviated as QOL, can be evaluated by various questionnaires, which are classified as generic and disease-targeted ones. Generic questionnaires are further subdivided into profile-type and preference-based ones. SF-36 and EQ-5D are the best known examples for the former and the latter, respectively. In SF-36 and its shortened one SF-8, the subjects' QOL is expressed by several profiles or subscales. Their advantages include well conducted validation and availability of national norms. In EQ-5D, a single value representing the subjects' QOL status (utility) is obtained through 5 questions. These generic questionnaires are applicable to patients with various diseases or even to healthy citizens. In contrast, disease-targeted questionnaires lack such features, but can include items that are specifically related to the disease but devoid of general applicability. Thus, generic and disease-targeted questionnaires have their own pros and cons. Selection of the questionnaires depends on the object of the study. PMID- 22298083 TI - Missing link between aortic wall pathology and aortic diameter: methodological bias or worrisome finding? PMID- 22298084 TI - Phosphatase PTEN is critically involved in post-myocardial infarction remodeling through the Akt/interleukin-10 signaling pathway. AB - The inflammatory cytokines interleukin (IL)-10 and tumor necrosis factor (TNF) alpha play an important role in left ventricular (LV) remodeling after myocardial infarction (MI). Phosphatase and tensin homolog deleted on chromosome ten (PTEN) inactivates protein kinase Akt and promotes cell death in the heart. However, it is not known whether PTEN promotes post-MI remodeling by regulating IL-10 and TNF alpha. MI was induced in wild-type (WT) mice and Pten heterozygous mutant (HET) mice. Pten adenoviruses (adPten) or empty vectors (adNull) were injected into the peri-infarct area of WT mice. LV dilation was attenuated and fractional shortening was increased in HET mice compared to WT mice. Survival rate and fractional shortening were decreased in adPten mice compared to adNull mice. Leukocyte infiltration into the peri-infarct area was attenuated in HET mice and worsened in adPten mice. PTEN expression was upregulated in the infarcted heart of WT mice. Partial inactivation of PTEN increased the production of IL-10 and decreased the expression of TNF-alpha and matrix metalloproteinase (MMP)-2 and -9 after MI in HET mice. PTEN overexpression caused opposite effects in the infarcted heart. Moreover in the infarcted heart of HET mice, Akt inhibition decreased Stat3 phosphorylation and IL-10 expression, and blockade of the IL-10 receptor increased TNF-alpha and MMP-2 expression. Both Akt inhibition and IL-10 receptor blockade abolished the attenuation of post-MI remodeling in HET mice. In conclusion, PTEN is critically involved in post-MI remodeling through the Akt/IL 10 signaling pathway. Therefore, targeting PTEN may be an effective approach to post-MI remodeling. PMID- 22298085 TI - Insulin resistance impairs viral dynamics independently of ethnicity or genotypes. AB - BACKGROUND AND AIM: Data concerning the influence of insulin resistance (IR) and ethnicity on early phases of viral kinetics after initiation of peginterferon plus ribavirin in treatment-naive, chronic hepatitis C (CHC) patients are limited. METHODS: A total of 263 nondiabetic CHC patients treated with peginterferon plus ribavirin were enrolled for analysis from an Egyptian and Spanish center. IR was evaluated by homeostasis model assessment (HOMA)-IR. Hepatitis C virus (HCV) RNA levels were measured at baseline, 48 hours, 2, 4, and 12 weeks after treatment initiation. Sustained virological response (SVR) was examined 24 weeks after therapy discontinuation. RESULTS: Baseline HOMA-IR strongly influenced 48 hours viral dynamics. HCV-RNA decay observed at 48 hours after the first injection of peginterferon was significantly lower (0.91+/-0.51 log) in patients with HOMA >=2 compared with those with HOMA <2 (1.8+/-0.95 log, P=0.005) this effect was independent of stage of liver fibrosis, HCV genotype, and ethnicity. These differences remained with several cutoffs such as HOMA >3 or HOMA >4. Multivariate analysis identified baseline insulin levels as the main independent variable affecting the 48-hour response in addition to baseline HCV RNA. The difference in early viral kinetics between patients with HOMA >=2 or <2 is associated with a significant difference in the percentage of patients achieving both rapid virological response and SVR. CONCLUSIONS: IR is a major determinant of the early viral kinetic response to peginterferon plus ribavirin, which has a great impact on subsequent rapid virological response and SVR in CHC patients. This suggests that strategies to improve IR may have a positive effect on SVR and may be early monitored. PMID- 22298086 TI - TCRbeta clonality improves diagnostic yield of TCRgamma clonality in refractory celiac disease. AB - BACKGROUND: Refractory celiac disease (RCD) is a preneoplastic condition as many patients develop an enteropathy-type T-cell lymphoma, a mature T-cell receptor alpha-beta lymphoma arising in the gut with an ominous outcome. Recently, research focused on a population of intraepithelial intestinal lymphocytes expressing the same lymphoma T-cell receptor variable region (V)gamma, as shown by polymerase chain reaction (PCR) analysis and sequencing. Meanwhile, the Biomedicine and Health-2 Concerted Action has made available standardized, highly specific, and sensitive PCR assays not only for Vgamma but also for Vbeta. GOALS: We verified whether analyzing both rearrangements in duodenal biopsies from RCD patients increases the diagnostic accuracy of this method. STUDY: Duodenal biopsies were analyzed from 15 RCD patients, 21 negative controls, and 2 positive controls (enteropathy-type T-cell lymphoma complicating celiac disease). Multiplex clonality analyses were performed according to the Biomedicine and Health-2 protocols. PCR products were cloned and sequenced. RESULTS: Monoclonal rearrangements were found in 5/15 samples from patients with RCD (both rearrangements in 2 cases, Vbeta only in 2, and only 1 solitary Vgamma clonality). Monoclonality was found in 4/8 of the RCD patients who subsequently died, whereas only 1/7 of the patients still alive presented a monoclonal rearrangement. Positive controls revealed both monoclonal rearrangements; rearrangements were not detected in 20 of 21 negative controls. Sequencing of the amplified fragments confirmed the results. CONCLUSIONS: The combined analysis of both rearrangements allowed recognition of monoclonal populations in otherwise negative patients, with detection rates from 20% (Vgamma only) to 33% (Vgamma and Vbeta), thus raising the likelihood of early identification of RCD patients at high risk of death. PMID- 22298087 TI - Second-look endoscopy for bleeding peptic ulcer disease: a decision-effectiveness and cost-effectiveness analysis. AB - BACKGROUND: Second-look endoscopy after initial therapeutic endoscopy for bleeding peptic ulcer disease may decrease the risk of rebleeding; however, it is not recommended routinely. Understanding conditions under which second-look endoscopy is beneficial might be useful for clinical decision making. METHODS: Using a decision model, literature-based probabilities, and Medicare reimbursement costs, we compared routine second-look endoscopy with no second look endoscopy. We measured rebleeding, need for surgery, hospital mortality, and costs, and calculated the cost to avoid each outcome, expressed as the number needed to treat, along with the cost per outcome prevented. RESULTS: In the base case, routine second-look endoscopy reduced rebleeding from 16% to 10% (needed to treat=16) but had no effect on other outcomes. The cost to prevent 1 case of rebleeding was nearly $13,000. Threshold analysis revealed a rebleeding threshold of 31% to neutralize the cost difference between routine second-look endoscopy and no routine second-look endoscopy. If routine second-look endoscopy was 100% effective in preventing rebleeding, then the rebleeding threshold for cost neutrality would be 17.5%. When rebleeding risks after the index endoscopy and second-look endoscopy were simultaneously considered, the cost per bleed prevented ranged from a cost savings of $165 when the respective risks were 25% and 5%, to a cost of nearly $33,000 when the risks were 20% and 15%. CONCLUSIONS: The results suggest that routine second-look endoscopy is not indicated after therapeutic endoscopy for bleeding peptic ulcer disease. However, if rebleeding risk is 31% or greater, then routine second-look endoscopy reduces this risk at no additional cost. PMID- 22298088 TI - Long-term clinical outcomes and factors predictive of relapse after 5 aminosalicylate or sulfasalazine therapy in patients with intestinal Behcet disease. AB - BACKGROUND: Currently, 5-aminosalicylic acid (5-ASA)/sulfasalazine is used to empirically treat patients with intestinal Behcet disease (BD) without clear clinical evidence. In this study, we investigated long-term clinical outcomes and predictors of clinical relapse in patients with intestinal BD receiving 5 ASA/sulfasalazine maintenance therapy. METHODS: We reviewed the medical records of all the patients with intestinal BD, who received 5-ASA/sulfasalazine therapy in a single tertiary academic medical center between March 1986 and January 2011. The cumulative probabilities of clinical relapse after remission were calculated using the Kaplan-Meier method. Predictors of clinical relapse were identified by univariate analysis using the log-rank test and by multivariate analysis using Cox proportional hazards regression models. RESULTS: Among the 143 patients enrolled, 46 (32.2%) had a clinical relapse while they were being treated with 5 ASA/sulfasalazine therapy. The cumulative relapse rates at 1, 3, 5, and 10 years after remission were 8.1%, 22.6%, 31.2%, and 46.7%, respectively. By multivariate analysis, a younger age (<35 y) at the time of diagnosis, higher C-reactive protein level (>=1.5 mg/dL), and a higher disease activity index for intestinal Behcet disease score (>=60) at the time of 5-ASA/sulfasalazine initiation were independent predictors of relapse in patients with intestinal BD receiving 5 ASA/sulfasalazine maintenance therapy. CONCLUSIONS: This study has shown that 5 ASA/sulfasalazine therapy has a positive effect in maintaining remission in patients with intestinal BD. However, a younger age (<35 y), higher C-reactive protein level (>=1.5 mg/dL), and a higher disease activity index for intestinal Behcet disease score (>=60) were associated with a poor response to 5 ASA/sulfasalazine therapy, making careful observation and intensive treatment necessary in these risk groups. PMID- 22298089 TI - Proton pump inhibitor use and recurrent Clostridium difficile-associated disease: a case-control analysis matched by propensity score. AB - BACKGROUND AND AIM: Clostridium difficile has been increasingly diagnosed in hospitalized patients. An association between proton pump inhibitors (PPIs) use and Clostridium difficile-associated disease (CDAD) and between recurrent CDAD has been suggested. The aim of this study is to investigate whether PPI use is associated with the development of recurrent CDAD. METHODS: This was a retrospective case-control study of patients with CDAD at Yeungnam University Medical Center, seen from January 2004 to December 2008. C. difficile infection was diagnosed by the presence of C. difficile toxin in the stool. Those with recurrent disease were matched with nonrecurrent controls using multivariate matched sampling methods that incorporated the propensity score. RESULTS: Recurrent CDAD developed in 28 (14.1%) of the 198 patients with diarrhea and positive C. difficile stool toxin assays. Multivariate analysis of the total population of recurrent versus nonrecurrent CDAD revealed that additional use of non-C. difficile antimicrobial therapy (concomitant with the treatment or after or both), poor response to therapy with metronidazole or vancomycin, and recent gastrointestinal surgery were risk factors for recurrent CDAD. We were able to match 21 recurrent CDAD subjects with 21 without recurrent CDAD. Among the matched patients only PPI use was associated with recurrent CDAD (ie, 47.6% vs. 4.8%, P=0.004 for recurrent vs. nonrecurrent CDAD, respectively). CONCLUSIONS: Among the matched patient groups, only PPI therapy was associated with recurrent CDAD. Prospective studies are needed to clarify whether avoidance of PPIs or specific cotherapies will reduce the incidence of recurrent C. difficile associated diarrhea. PMID- 22298090 TI - Association of helicobacter pylori dupA with the failure of primary eradication. AB - GOALS: To determine whether the presence of dupA Helicobacter pylori (H. pylori) influences the cure rate of primary eradication therapy. BACKGROUND: Several virulence factors of H. pylori have been reported to affect the efficacy of the eradication rate. However, no study has investigated whether the presence of dupA affects eradication failure. STUDY: The presence of dupA was evaluated in 142 H. pylori strains isolated from 142 patients with gastrointestinal diseases. Of these patients, 104 received primary eradication therapy for 1 week. The risk factors for eradication failure were determined using univariate and multivariate analyses. RESULTS: Among 142 strains, 44 (31.0%) were dupA positive. There was no association between dupA status and gastroduodenal diseases (P>0.05). The clarithromycin (CLR) resistance rate was generally lower in the dupA-positive than in the dupA-negative group (20.4% vs. 35.7%, P=0.06). However, dupA prevalence was higher in the eradication failure group than in the success group (36.3% vs. 21.9%). Among the CLR-resistant H. pylori infected group, the successful eradication rate was significantly lower in patients infected with dupA-positive H. pylori than dupA-negative H. pylori (P=0.04). In multivariate analysis adjusted for age, sex, and type of disease, not only CLR resistance but also dupA presence was independent risk factors for eradication failure (adjusted odds ratio=3.71; 95% confidence interval,1.07-12.83). CONCLUSIONS: Although CLR resistant was more reliable predictor, the presence of dupA may also be an independent risk factor for eradication failure. PMID- 22298091 TI - Communicative perspective-taking performance of adults with ADHD symptoms. AB - OBJECTIVE: The ability to take the perspective of one's conversational partner is essential for successful communication. Given the significant cognitive and attention resources required to use another's perspective, the authors assessed whether adults who report symptoms of ADHD would have difficulty using their conversational partner's visual perspective to guide their interpretations. METHOD: Adults with high (clinical range) or low (nonclinical range) self reported ADHD symptoms participated in a communication task that required perspective-taking. RESULTS: Eye movement measures revealed that individuals with high ADHD symptoms fixated on objects obscured from their partners' view more often than did those participants with low ADHD symptoms, and the degree to which this "egocentric" object was considered correlated with the degree of inattention symptoms. However, overt behavior (object choice) was not impacted by ADHD symptomatology. CONCLUSION: Individuals with high levels of ADHD symptoms, especially inattention, are less efficient in their ability to use another's perspective during conversation. PMID- 22298092 TI - Pre- and postnatal risk factors for ADHD in a nonclinical pediatric population. AB - OBJECTIVE: The authors characterized pre- and postnatal risk factors for ADHD among a population-based sample of 8-year-old children followed since birth (N = 604). METHOD: Parents and teachers rated ADHD symptoms, including inattention and impulsivity/hyperactivity. The authors reviewed pediatric medical records for history of an ADHD diagnosis, and parents reported ADHD medication use. The authors analyzed risk factors in relationship to outcomes using multivariable regression models. RESULTS: Low paternal education, prenatal smoking, prenatal illicit drug use, maternal depression, and low Home Observation for Measurement of the Environment score were associated with greater risk for ADHD behaviors assessed via rating scale. Low income and being male were associated with ADHD diagnosis in medical records and ADHD medication use. CONCLUSION: The authors found associations between socioeconomic, psychosocial, and prenatal exposures and ADHD-related behavior. Selection bias due to access to care and recall bias from inaccurate report of past exposures is minimized in this large, nonclinical, prospective cohort study. PMID- 22298093 TI - A revolution in an Egyptian hospital. PMID- 22298094 TI - Are we prepared to sacrifice good feeling for pensions? PMID- 22298095 TI - Lessons from America: primary care. PMID- 22298096 TI - Matters of life and death and quality of life. PMID- 22298097 TI - Why legislation is necessary for my health reforms. PMID- 22298098 TI - Advanced endosonographic diagnostic tools for discrimination of focal chronic pancreatitis and pancreatic carcinoma--elastography, contrast enhanced high mechanical index (CEHMI) and low mechanical index (CELMI) endosonography in direct comparison. AB - New tools have recently emerged that further improve the diagnostic performance of high-end endosonography. Whilst elastography has been available for a while, contrast-enhancing techniques are still very young with little experience existing in this field. The latest development is contrast enhanced low mechanical index endosonography (CELMI-EUS) which became commercially available at the beginning of 2010. This technique requires contrast-specific software whereas the pre-existing technique of contrast-enhanced high mechanical index endosonography (CEHMI-EUS) does not. The aim of this study was to compare these techniques in discriminating between focal chronic pancreatitis and pancreatic carcinoma. Included in the study were 58 patients with a pancreatic lesion (19 pancreatic cancer and 39 chronic pancreatitis) with a mean age of 60+/-15 years. All patients were examined by one investigator (MH). All methods were performed within one examination and the result of each technique was noted before using the next. The gold standard was pathology following surgery, endoscopic fine needle puncture, or one-year follow-up when chronic pancreatitis was suspected. The consecutive results of specificity and sensitivity were 73.7% and 61.5% for B mode endosonography; 94.7% and 33.4% for elastography; 84.2% and 76.9% for CELMI EUS; and 89.5% and 92.3% for CEHMI-EUS. A combination of 3 of those methods could not improve on the result of CEHMI-EUS alone. This study shows that, despite the availability of new technologies, CEHMI-EUS is still the most reliable method for the differentiation of focal chronic pancreatitis and pancreatic carcinoma. However, understanding the advantages of the different methods might help to find the optimal indications for the use of the new techniques. PMID- 22298099 TI - [Endoscopy in geriatric patients: position paper of the working group geriatric gastroenterology]. AB - The relevance of endoscopic diagnostic and therapeutic interventions is on a constant rise. However, specific aspects of the treatment of geriatric patients have only been tackled to a rather limited extent so far. The present contribution pinpoints illustratively the status quo on this issue and provides directions for further research which should be conducted in future studies supported by the working group on geriatric gastroenterology. PMID- 22298100 TI - [Segmental necrotizing colitis in a patient with E. coli O104:H4 infection]. AB - A 29-year-old man presented with abdominal cramps and bloody diarrhoea. Blood tests revealed elevated C-reactive protein (21.3 mg/dL; normal range 0.01 - 0. 82 mg/dL) and white blood cells (28200/MUL, normal range 4000 - 10000/MUL). Stool tests were negative for enteropathogenic bacteria and Clostridium difficile toxins A/B. Ultrasound and computed tomography showed massive swelling of the transverse colon and right colonic flexure. At endoscopy, circular necrosis of the mucosa was encountered in the proximal segments of the colon whereas distal parts of the organ showed patchy inflammation of minor severity. Extended stool testing identified Escherichia coli type O104:H4 as the causative microorganism. There was no evidence for haemolytic uraemic syndrome. Under conservative treatment the patient recovered clinically, serologically and endoscopically. At follow-up endoscopy, longitudinal ulcers and vital mucosa were present. In this case report the segmental pattern of mucosal necrosis in a patient with EHEC infection is noteworthy. PMID- 22298101 TI - Knotting of percutaneous endoscopic jejunostomy feeding tubes in two patients with Parkinson's disease and continuous Duodopa(r) treatment. AB - Continuous intraduodenal infusion of levodopa/carbidopa (Duodopa(r)) via PEJ tubes is increasingly used in patients with advanced stages of Parkinson's disease. Tube-related complications such as kinking or coiling have been frequently reported. We herein describe two cases of tube dysfunction in patients with Parkinson's disease and continuous Duodopa(r) treatment due to knotting of the distal end of the tube. The mechanisms of knotting are unclear although a causative role of impaired gastrointestinal motility either by Parkinson's disease itself or Duodopa(r) treatment might be suspected. PMID- 22298102 TI - [Lynch syndrome--epidemiology, clinical features, molecular genetics, screening, therapy]. AB - Lynch syndrome is characterised by a familial predisposition of colorectal and endometrial carcinomas in association with a variety of other cancers. The underlying autosomal dominant inheritance has a penetrance of 85-90%. The molecular genetic underlying mechanism is a mutation in one of the mismatch repair genes. The identification of the molecular genetic basis of Lynch syndrome enabled the implementation of predictive testing in families with a proven mutation. A prerequisite to detect patients with Lynch syndrome is a knowledge of the clinical and histopathological features of this disease. Typical for Lynch syndrome associated carcinomas is the early age of onset of about 45 years as well as the characteristic localisation within the right hemicolon. However, in order to increase the rate of identification of this underestimated syndrome, the awareness of the clinician must extend beyond this classical phenotype. For this purpose close interdisciplinary cooperation is warranted! The cancers are mostly low-differentiated with solid areas without a tubular structure. Crohn's-like lesions as well as peritumoural and tumour-infiltrating lymphocytes may frequently be found in the periphery of the malignant formation. Within the framework of the clinical evaluation of any index patient, an extended family history must be ascertained and matched with the Amsterdam-I and -II criteria as well as with the revised Bethesda criteria. If a patient fulfills these criteria, testing for microsatellite instability and if positive after genetic counselling mutation analysis should be recommended. Patients with a proven mutation and high risk individuals from families with an unidentified underlying mutation are encouraged to participate in an intensified screening programme. Due to the incomplete penetrance there is no recommendation towards prophylactic surgery in high-risk individuals without tumour manifestation. Nevertheless, the effect on quality of life of prophylactic, extended surgery in addition to the obligatory oncologic resection with or without prophylactic hysterectomy needs to be established in prospective controlled trials. PMID- 22298103 TI - Biliary papillomatosis and new ultrasound imaging modalities. AB - Biliary papillomatosis (BP) is a rare disorder of the biliary tract with a significant risk of malignant transformation and a high recurrence rate after operation due to the diffuse distribution of the disease. Preoperative diagnosis is difficult also by reason of the low sensitivity and specificity of conventional ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), endoscopic retrograde cholangiography (ERC) and positron emission tomography (PET). Therefore, the introduction of new diagnostic imaging methods is of importance to improve the preoperative diagnosis of this originally as benign described disease which is reflected in the term of "benign papillomatosis of the biliary tree". The present review summarizes the literature and discusses new sonographic imaging techniques including contrast-enhanced ultrasound (CEUS), contrast-enhanced low mechanical endoscopic ultrasound (CELMI-EUS) and endoscopic ultrasound elastography. PMID- 22298104 TI - [Risk reduction of hepatocellular carcinoma by metformin--time for a change of paradigm?]. PMID- 22298105 TI - Carbon monoxide-controlled synthesis of surface-clean Pt nanocubes with high electrocatalytic activity. AB - A new strategy for synthesis of Pt nanocubes on various supports by reduction of a Pt precursor under a CO atmosphere was described. The as-prepared Pt nanocubes supported on multi-walled carbon nanotubes exhibited high activity toward methanol electrooxidation. PMID- 22298106 TI - What are new avenues for renal protection, in addition to RAAS inhibition? AB - Diabetic nephropathy is the leading cause of endstage renal disease, with both the incidence and prevalence continuing to increase worldwide. Current treatments include optimization of glycemic and blood pressure control by targeting the renin-angiotensin-aldosterone system (RAAS) with angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin II receptor blockers. More innovative strategies are needed to prevent and treat this disease. New agents and approaches have recently been described that have the potential to delay the progression of diabetic kidney disease and minimize the growing burden of endstage renal disease. Possible targets include the formation of advanced glycation end products (AGEs) and the AGE receptor, increased oxidative stress and inflammation, protein kinase C, endothelin receptors, growth factors and cytokines, the vitamin D receptor, Rho-associated kinases, and the renal sympathetic system. This article reviews these recent developments as potential therapeutic interventions that may prevent this disease, with targets generally beyond the RAAS. PMID- 22298107 TI - Correlates of Attachment Perceptions in Parents of Children with Autism Spectrum Disorders. AB - This study explored the relationship between parents' perceptions of their child's attachment to them and parents' own affective attachment to their child, as well the relationship of these constructs to parenting stress, parent-rated child functional impairment, and parenting sense of competence. Mothers (n = 76) and fathers (n = 30) of children ages 2-10 with autism spectrum disorders participated. Overall, parents' affective attachment to their child was more consistently related to other aspects of their parenting experiences than were their perceptions of their child's attachment to them. Also, perceptions of child to-parent attachment were related to other aspects of parenting for fathers more than for mothers. Implications for parenting interventions and future research, such as longitudinal investigations, are discussed. PMID- 22298108 TI - Do Children with Specific Language Impairment have a Cognitive Profile Reminiscent of Autism? A Review of the Literature. AB - There is debate regarding the relationship between autism and specific language impairment (SLI), with some researchers proposing aetiological overlap between the conditions and others maintaining their aetiological distinction. Although considerable research has investigated the language phenotypes of these disorders, the relationship between the cognitive phenotypes has been left relatively unexplored. This paper reviews relevant literature on whether individuals with SLI exhibit cognitive characteristics reminiscent of autism. Overall, findings are inconsistent and there is a lack of substantive evidence supporting overlapping cognitive phenotypes in autism and SLI. Better powered and more rigorous experimental designs, as well as studies directly comparing the cognitive phenotype of children with SLI and those with autism will further elucidate the aetiological relationship between these two conditions. PMID- 22298109 TI - MudPIT analysis of released proteins in Pseudomonas aeruginosa laboratory and clinical strains in relation to pro-inflammatory effects. AB - Pseudomonas aeruginosa (Pa) is the most common virulent pathogen contributing to the pathogenesis of cystic fibrosis (CF). During bacterial lung colonization, the products of its metabolism are released in the extracellular space contributing to the pathogenic events associated with its presence. To gain insights on the mechanisms involved in the Pa pathogenesis we focused our attention on proteins released by Pa using a MudPIT approach combined with cell biology assays. Conditioned medium (CM) collected under aerobic and microaerobic conditions from Pa clinical strains (in early and late colonization), unlike the laboratory strain, induced expression of IL-8 mRNA in CF airway epithelial cells. We have identified proteins released by clinically relevant Pa strains, focusing on the pro-inflammatory effects as metalloproteases (MMPs). In fact, their expression pattern was associated with the highest pro-inflammatory activity measured in the early clinically isolated strain. The relation was further supported by the result of the analysis of a larger and independent set of Pa isolates derived from sporadically and chronically infected CF patients: 76% of sporadic samples expressed protease activity (n = 44), while only 27% scored positive in the chronically infected individuals (n = 38, p < 0.0001, Fisher's exact test). Finally, looking for a possible mechanism of action of bacterial MMPs, we found that CM from early clinical isolates can cleave CXCR1 on the surface of human neutrophils, suggesting a potential role for the bacterially released MMPs in the protection of the pathogen from the host's response. PMID- 22298110 TI - The effect of tree species diversity on fine-root production in a young temperate forest. AB - The phenomenon of overyielding in species-diverse plant communities is mainly attributed to complementary resource use. Vertical niche differentiation belowground might be one potential mechanism for such complementarity. However, most studies that have analysed the diversity/productivity relationship and belowground niche differentiation have done so for fully occupied sites, not very young tree communities that are in the process of occupying belowground space. Here we used a 5-6 year old forest diversity experiment to analyse how fine-root (<2 mm) production in ingrowth cores (0-30 cm) was influenced by tree species identity, as well as the species diversity and richness of tree neighbourhoods. Fine-root production during the first growing season after the installation of ingrowth cores increased slightly with tree species diversity, and four-species combinations produced on average 94.8% more fine-root biomass than monocultures. During the second growing season, fine-root mortality increased with tree species diversity, indicating an increased fine-root turnover in species-rich communities. The initial overyielding was attributable to the response to mixing by the dominant species, Pseudotsuga menziesii and Picea abies, which produced more fine roots in mixtures than could be expected from monocultures. In species rich neighbourhoods, P. abies allocated more fine roots to the upper soil layer (0-15 cm), whereas P. menziesii produced more fine roots in the deeper layer (15 30 cm) than in species-poor neighbourhoods. Our results indicate that, although there may be no lasting overyielding in the fine-root production of species diverse tree communities, increasing species diversity can lead to substantial changes in the production, vertical distribution, and turnover of fine roots of individual species. PMID- 22298111 TI - Tadpole mortality varies across experimental venues: do laboratory populations predict responses in nature? AB - Laboratory experiments are widely used to study how populations in nature might respond to various biological interactions, but the relevance of experiments in artificial venues is not known. We compiled mortality and growth data from 424 anuran populations carried out under laboratory, mesocosm, field enclosure, and field settings to determine if major differences exist amongst experimental venues and how this might influence experimental responses of tadpoles amongst venues. Our results show that there are fundamental differences in survival amongst venues, with the highest mortality occurring in field populations and the lowest in laboratory populations. Separation of mesocosm and field enclosure data based on the possibility of predatory interactions indicates that predation is an important factor leading to increased mortality in natural populations. Comparisons of size distributions across venues (although size data were limited for field populations) suggest that variation in tadpole size is low in natural populations compared to populations in artificial venues. We infer from this that mortality has a homogenizing effect on size in nature, resulting in natural populations that are not a random sample of hatched individuals. This finding suggests that populations reared under controlled laboratory conditions in the absence of predation (and other selective pressures) may not be representative of natural populations. PMID- 22298112 TI - Aquatic life water quality criteria derived via the UC Davis method: I. Organophosphate insecticides. AB - A new methodology for deriving freshwater aquatic life water quality criteria,developed by the University of California Davis, was used to derive criteria for three organophosphate insecticides. The UC Davis methodology resulted in similar criteria to other accepted methods, and incorporated new approaches that enable criteria generation in cases where the existing USEPA guidance cannot be used.Acute and chronic water quality criteria were derived for chlorpyrifos (10 and 10 ng/L, respectively), diazinon (200 and 70 ng/L, respectively), and malathion(170 and 28 ng/L, respectively). For acute criteria derivation, Burr Type III SSDs were fitted to the chlorpyrifos and diazinon acute toxicity data sets while an alternative assessment factor procedure was used for malathion because that acute data set did not contain adequate species diversity to use a distribution.ACRs were used to calculate chronic criteria because there was a dearth of chronic data in all cases, especially for malathion, for which there was a lack of paired acute and chronic invertebrate data. Another alternate procedure enabled calculation of the malathion chronic criterion by combining a default ratio with the experimentally derived ratios. A review of the diazinon chronic criterion found it to be under protective of cladoceran species, so a more protective criterion was calculated using a lower distributional estimate. The acute and chronic data sets were assembled using a transparent and consistent system for judging the relevance and reliability of studies, and the individual study review notes are included.The resulting criteria are unique in that they were reviewed to ensure particular protection of sensitive and threatened and endangered species, and mixture toxicity is incorporated into criteria compliance for all three compounds.For chlorpyrifos and diazinon, the UCDM generated criteria similar to the long-standing USEPA (1985) method, with less taxa requirements, a more statistically robust distribution, and the incorporation of new advances in risk assessment and ecotoxicology. According to the USEPA (1985) method, the data set gathered for malathion would not be sufficient to calculate criteria because it did not contain data for a benthic crustacean. Benthic crustacean data is also required to use a distributional calculation method by the UCDM, but when data is lacking the UCDM provides an alternate calculation method." The resulting criteria are associated with higher, unquantifiable uncertainty, but they are likely more accurate than values generated using static safety factors, which are currently common in risk assessment. PMID- 22298113 TI - Aquatic life water quality criteria derived via the UC Davis method: II. Pyrethroid insecticides. AB - Aquatic life water quality criteria were derived for five pyrethroids using a new methodology developed by the University of California, Davis (TenBrook et al.2010). This methodology was developed to provide an updated, flexible, and robust water quality criteria derivation methodology specifically for pesticides. To derive the acute criteria, log-logistic SSDs were fitted to the medium-sized bifenthrin,cyfluthrin, and cypermethrin acute toxicity data sets while the X cyhalothrin and permethrin acute data sets were larger, and Burr Type III SSDs could be fitted to these data sets. A review of the cyfluthrin acute criterion revealed that it was not protective of the most sensitive species in the data set, H. azteca, so the acute value was adjusted downward to calculate a more protective criterion. Similarly, the cypermethrin criteria were adjusted downward to be protective of H. azteca.Criteria for bifenthrin, X-cyhalothrin, and permethrin were calculated using the median fifth percentile acute values while the cyfluthrin and cypermethrin criteria were calculated with the next lowest acute value (median first percentile). Chronic data sets were limited in all cases, so ACRs were used for chronic criteria calculations, instead of statistical distributions. Sufficient corresponding acute and chronic data were not available for bifenthrin, cypermethrin, or permethrin, so a default ACR was used to calculate these chronic criteria while measured ACRs were used for cyfluthrin and X-cyhalothrin. A numeric scoring system was used to sort the acute and chronic data, based on relevance and reliability, and the individual study scores are included in the Supporting Information.According to the USEPA (1985) method, the data sets gathered for these five pyrethroids would not be sufficient to calculate criteria because they were each missing at least one of the eight taxa required by that method. The USEPA (1985)method generates robust and reliable criteria, and the goal of creating the UCDM was to create a method that also yields statistically robust criteria, but with more flexible calculation methods to accommodate pesticide data sets of varied sizes and diversities. Using the UCDM, acute and chronic water quality criteria were derived for bifenthrin (4 and 0.6 ng/L, respectively), cyfluthrin (0.3 and 0.05 ng/L, respectively), cypermethrin (1 and 0.2 ng/L, respectively), X-cyhalothrin (1 and 0.5 ng/L,respectively), and permethrin (10 and 2 ng/L, respectively). Water quality criteria for these five pyrethroids can be used by environmental managers to control the increasing problem of surface water contamination by pesticides. PMID- 22298114 TI - Aquatic life water quality criteria derived via the UC Davis method: III. Diuron. PMID- 22298115 TI - Effects of the cyclin-dependent kinase 10 (CDK10) on the tamoxifen sensitivity of keloid samples. AB - Cyclin-dependent kinase 10 (CDK10) is a cell cycle regulating protein kinase, which has just been discriminated in recent years. In this paper, mRNA and protein expression of CDK10 were first investigated by a comparative study between 23 human keloid tissue samples and their adjacent normal skin. To further address its potential as a therapeutic target in the treatment of keloid, a plasmid expressing the CDK10 gene was transfected into keloid fibroblast. The effects on tamoxifen-induced apoptosis were then investigated using Western blot assay and flow cytometry. Results showed that there is a generally down-regulated expression of CDK10 in keloid compared to normal skin samples. Transfection with the recombinant CDK10 plasmid significantly decreased the viability of cells and increased the apoptosis rates. Tamoxifen sensitivity in keloid fibroblasts was observed after treatment with the recombinant CDK10 plasmid. The results suggested that CDK10 may play an important role in enhancement of tamoxifen efficiency, and its expression may have a synergistic effect on keloid treatments. PMID- 22298116 TI - Microfiltration process by inorganic membranes for clarification of TongBi liquor. AB - Membrane separation is an alternative separation technology to the conventional method of filtration. Hence, it has attracted use in the purification and concentration of Chinese Herbal Medicine Extracts (CHMEs). The purpose of this work was to study the process of microfiltration of Tongbi liquor (TBL), a popular Chinese herbal drink, using ceramic membranes. Zirconium oxide and aluminum oxide membranes with pore mean sizes of 0.2 MUm and 0.05 MUm, respectively, are used for comparisons in terms of flux, transmittance of the ingredients, physical-chemical parameters, removal of macromolecular materials and fouling resistance. The results show that 0.2 MUm zirconium oxide membrane is more suitable. The stable permeate flux reaches 135 L.h(-1).m(-2), the cumulative transmittance of the indicator is 65.53%. Macromolecular materials, such as starch, protein, tannin, pectin and total solids were largely eliminated in retentate after filtration using 0.2 MUm ZrO2 ceramic membrane, resulting in clearer TBL. Moreover, this work also reveals that continuous ultrasound could strengthen membrane process that the permeate flux increases significantly. This work demonstrates that the purification of CHME with ceramic membranes is possible and yielded excellent results. PMID- 22298117 TI - Pushing the boundaries: frontiers of quality of life research. Abstracts of the 18th Annual Conference of the International Society for Quality of Life Research. October 26-29, 2011. Denver, Colorado, USA. PMID- 22298119 TI - Dysregulation of circulating microRNAs and prediction of aggressive prostate cancer. AB - BACKGROUND: It is becoming increasingly evident that microRNAs (miRNAs) are associated with the development and progression of prostate cancer (PCa). METHODS: We examined the hypothesis that plasma miRNA levels can differentiate patients by aggressiveness in 82 PCa patients. Taqman based quantitative RT-PCR assays were performed to measure copy number of target miRNAs. RESULTS: miR-20a was significantly overexpressed in plasma from patients with stage 3 tumors compared to stage 2 or below (P = 0.03). The expression levels for miR-20a and miR-21 were significantly increased in patients with high risk CAPRA scores (16,623 and 1,595 copies, respectively). Significantly increased miR-21 and miR 145 expression were observed for patients with intermediate or high risk D'Amico scores compared to patients with low risk scores (P = 0.047 and 0.011, respectively). The relapse rates for CAPRA scores ranged from 1.9% for low risk to 9.5% for intermediate risk and to 22.2% for high risk patients (P = 0.023). For D'Amico scores, the relapse rates ranged from 0.0% for low risk to 7.4% for intermediate risk and 17.6% for high risk patients (P = 0.039). Expression of miR 21 and miR-221 significantly differentiated patients with intermediate risk from those with low risk CAPRA scores (AUC = 0.801, P = 0.002). Four miRNAs (miR-20a, miR-21, miR-145, and miR-221) could also distinguish high versus low risk in PCa patients by D'Amico score with an AUC of 0.824. CONCLUSIONS: These preliminary data suggest that altered plasma miRNAs may be useful predictors to distinguish PCa patients with varied aggressiveness. Further larger studies to validate this promising finding are warranted. PMID- 22298121 TI - Course of improvement in depressive symptoms to a single intravenous infusion of ketamine vs add-on riluzole: results from a 4-week, double-blind, placebo controlled study. AB - The N-methyl-D-aspartate antagonist ketamine has rapid antidepressant effects in patients with treatment-resistant major depression (TRD); these effects have been reported to last for 1 week in some patients. However, the extent and duration of this antidepressant effect over longer periods has not been well characterized under controlled conditions. Riluzole, a glutamatergic modulator with antidepressant and synaptic plasticity-enhancing effects, could conceivably be used to promote the antidepressant effects of ketamine. This study sought to determine the extent and time course of antidepressant improvement to a single ketamine infusion over 4 weeks, comparing the addition of riluzole vs placebo after the infusion. Forty-two subjects (18-65) with TRD and a Montgomery-Asberg Depression Rating Scale (MADRS) score of >= 22 received a single intravenous infusion of ketamine (0.5 mg/kg). Four to six hours post-infusion, subjects were randomized to double-blind treatment with either riluzole (100-200 mg/day; n=21) or placebo (n=21) for 4 weeks. Depressive symptoms were rated daily. A significant improvement (P<0.001) in MADRS scores from baseline was found. The effect size of improvement with ketamine was initially large and remained moderate throughout the 28-day trial. Overall, 27% of ketamine responders had not relapsed by 4 weeks following a single ketamine infusion. The average time to relapse was 13.2 days (SE=2.2). However, the difference between the riluzole and placebo treatment groups was not significant, suggesting that the combination of riluzole with ketamine treatment did not significantly alter the course of antidepressant response to ketamine alone. PMID- 22298120 TI - Corticotropin-releasing factor modulation of forebrain GABAergic transmission has a pivotal role in the expression of anabolic steroid-induced anxiety in the female mouse. AB - Increased anxiety is commonly observed in individuals who illicitly administer anabolic androgenic steroids (AAS). Behavioral effects of steroid abuse have become an increasing concern in adults and adolescents of both sexes. The dorsolateral bed nucleus of the stria terminalis (dlBnST) has a critical role in the expression of diffuse anxiety and is a key site of action for the anxiogenic neuromodulator, corticotropin releasing factor (CRF). Here we demonstrate that chronic, but not acute, exposure of female mice during adolescence to AAS augments anxiety-like behaviors; effects that were blocked by central infusion of the CRF receptor type 1 antagonist, antalarmin. AAS treatment selectively increased action potential (AP) firing in neurons of the central amygdala (CeA) that project to the dlBnST, increased the frequency of GABA(A) receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in dlBnST target neurons, and decreased both c-FOS immunoreactivity (IR) and AP frequency in these postsynaptic cells. Acute application of antalarmin abrogated the enhancement of GABAergic inhibition induced by chronic AAS exposure whereas application of CRF to brain slices of naive mice mimicked the actions of this treatment. These results, in concert with previous data demonstrating that chronic AAS treatment results in enhanced levels of CRF mRNA in the CeA and increased CRF-IR in the dlBnST neuropil, are consistent with a mechanism in which the enhanced anxiety elicited by chronic AAS exposure involves augmented inhibitory activity of CeA afferents to the dlBnST and CRF-dependent enhancement of GABAergic inhibition in this brain region. PMID- 22298122 TI - Prevention of stress-impaired fear extinction through neuropeptide s action in the lateral amygdala. AB - Stressful and traumatic events can create aversive memories, which are a predisposing factor for anxiety disorders. The amygdala is critical for transforming such stressful events into anxiety, and the recently discovered neuropeptide S transmitter system represents a promising candidate apt to control these interactions. Here we test the hypothesis that neuropeptide S can regulate stress-induced hyperexcitability in the amygdala, and thereby can interact with stress-induced alterations of fear memory. Mice underwent acute immobilization stress (IS), and neuropeptide S and a receptor antagonist were locally injected into the lateral amygdala (LA) during stress exposure. Ten days later, anxiety like behavior, fear acquisition, fear memory retrieval, and extinction were tested. Furthermore, patch-clamp recordings were performed in amygdala slices prepared ex vivo to identify synaptic substrates of stress-induced alterations in fear responsiveness. (1) IS increased anxiety-like behavior, and enhanced conditioned fear responses during extinction 10 days after stress, (2) neuropeptide S in the amygdala prevented, while an antagonist aggravated, these stress-induced changes of aversive behaviors, (3) excitatory synaptic activity in LA projection neurons was increased on fear conditioning and returned to pre conditioning values on fear extinction, and (4) stress resulted in sustained high levels of excitatory synaptic activity during fear extinction, whereas neuropeptide S supported the return of synaptic activity during fear extinction to levels typical of non-stressed animals. Together these results suggest that the neuropeptide S system is capable of interfering with mechanisms in the amygdala that transform stressful events into anxiety and impaired fear extinction. PMID- 22298123 TI - Differential effects of cocaine on dopamine neuron firing in awake and anesthetized rats. AB - Cocaine (benzoylmethylecgonine), a natural alkaloid, is a powerful psychostimulant and a highly addictive drug. Unfortunately, the relationships between its behavioral and electrophysiological effects are not clear. We investigated the effects of cocaine on the firing of midbrain dopaminergic (DA) neurons, both in anesthetized and awake rats, using pre-implanted multielectrode arrays and a recently developed telemetric recording system. In anesthetized animals, cocaine (10 mg/kg, intraperitoneally) produced a general decrease of the firing rate and bursting of DA neurons, sometimes preceded by a transient increase in both parameters, as previously reported by others. In awake rats, however, injection of cocaine led to a very different pattern of changes in firing. A decrease in firing rate and bursting was observed in only 14% of DA neurons. Most of the other DA neurons underwent increases in firing rate and bursting: these changes were correlated with locomotor activity in 52% of the neurons, but were uncorrelated in 29% of them. Drug concentration measurements indicated that the observed differences between the two conditions did not have a pharmacokinetic origin. Taken together, our results demonstrate that cocaine injection differentially affects the electrical activity of DA neurons in awake and anesthetized states. The observed increases in neuronal activity may in part reflect the cocaine-induced synaptic potentiation found ex vivo in these neurons. Our observations also show that electrophysiological recordings in awake animals can uncover drug effects, which are masked by general anesthesia. PMID- 22298124 TI - Prebiotic effect of soluble fibres from modern and old durum-type wheat varieties on Lactobacillus and Bifidobacterium strains. AB - BACKGROUND: Wheat grains are a rich source of dietary fibres, particularly in the western human diet. Many of the health effects attributed to dietary fibres are believed to be related to their microbial fermentation in the gut. This study evaluated the ability of two potentially probiotic strains, Lactobacillus plantarum L12 and Bifidobacterium pseudocatenulatum B7003, to ferment soluble dietary fibres (SDFs) from modern and ancient durum-type wheat grains. RESULTS: Fibre microbial utilisation was highly variable and dependent on the strain. SDFs from the varieties Svevo and Solex supported the growth of L. plantarum L12 the best, whereas those from the varieties Anco Marzio, Solex and Kamut((r)) Khorasan were good carbohydrate substrates for B. pseudocatenulatum B7003. The highest prebiotic activity scores (describing the extent to which prebiotics support selective growth of probiotics) for B7003 were obtained with SDFs from the varieties Solex (0.57), Kamut((r)) Khorasan (0.56) and Iride (0.55), whereas for L12 the highest scores were achieved with the varieties Orobel (0.63), Kamut((r)) Khorasan (0.56) and Solex (0.53). CONCLUSION: The present study has identified some SDFs from durum-type wheat grains as suitable prebiotic substrates for the selective proliferation of B. pseudocatenulatum B7003 and L. plantarum L12 in vitro. The results provide the basis for the potential utilisation of wheat-based prebiotics as a component of synbiotic formulations. PMID- 22298125 TI - Soft tissue composition and the risk of low bone mineral density: the Fourth Korea National Health And Nutrition Examination Survey (KNHANES IV-3), 2009. AB - The effects of total fat mass (FM) and total lean mass (LM) on total bone mineral density (BMD) were examined using the Fourth Korea National Health and Nutrition Examination Survey, 2009. FM, LM, and BMD were measured by DXA in a population based sample of 6,762 Koreans, aged 19-93 (1,613 men < 50 years, 1,400 men >= 50 years, 2,120 premenopausal women, and 1,629 postmenopausal women). After adjusting for confounders (age, height, education, economic status, physical activity, smoking, alcohol use, serum vitamin D, medical history [diabetes, dyslipidemia, rheumatoid arthritis, and osteoporosis], family history of osteoporosis, multivitamin use, dietary intake [energy, calcium, and sodium], age at menarche, age at menopause, and hormone replacement therapy) and FM, higher LM was associated with a lower odds ratio for being in the group-specific lowest quintile of BMD (low BMD) in all groups. The odds for low BMD increased with higher FM in multivariate-adjusted analyses in men < 50 years, but this was not significant in other groups. Total BMD decreased with a decrease in the LM quintile across all FM subgroups in men of all ages, in the lower two subgroups of FM quintile in premenopausal women, and in the middle subgroup of FM quintile in postmenopausal women. In conclusion, higher LM was associated with a lower risk of low BMD in both genders, while higher FM was associated with a higher risk of low BMD for men < 50 years but not for women and men >= 50 years. The combined effects of LM and FM on BMD were gender- and menopause status-specific. PMID- 22298126 TI - Bullying at work and onset of a major depressive episode among Danish female eldercare workers. AB - OBJECTIVE: The aim of this study was to analyze whether exposure to workplace bullying among 5701 female employees in the Danish eldercare sector increases the risk of onset of a major depressive episode (MDE). METHODS: Participants received questionnaires in 2004-2005 and again in 2006-2007. MDE was assessed with the Major Depression Inventory. We examined baseline bullying as a predictor of onset of MDE at follow-up using multiple logistic regression. We further conducted a cross-sectional analysis at the time of follow-up among participants who at baseline were free of bullying, MDE, and signs of reduced psychological health. Finally, we analyzed reciprocal effects, by using baseline bullying and baseline MDE as predictors for bullying and MDE at follow-up. RESULTS: Onset rates of MDE in the groups of no, occasional, and frequent bullying were 1.5%, 3.4%, and 11.3%, respectively. Odds ratios (OR) for onset of MDE were 2.22 [95% confidence interval (95% CI) 1.31-3.76] for occasional bullying and OR 8.45 (95% CI 4.04 17.70) for frequent bullying, after adjustment for covariates. In the cross sectional analysis, OR were 6.29 (95% CI 2.52-15.68) for occasional bullying and 20.96 (95% CI 5.80-75.80) for frequent bullying. In the analyses on reciprocal effects, both baseline bullying [occasional: OR 2.12 (95% CI 1.29-3.48) and frequent: OR 6.39 (95% CI 3.10-13.17)] and baseline MDE [OR 7.18 (95% CI 3.60 14.30] predicted MDE at follow-up. However, only baseline bullying [occasional: OR 7.44 (95% CI 5.94-9.31) and frequent: OR 11.91 (95% CI 7.56-18.77)] but not baseline MDE [OR 0.93 (95% CI 0.47-1.84)] predicted bullying at follow-up. CONCLUSIONS: Workplace bullying increased the risk of MDE among female eldercare workers. MDE did not predict risk of bullying. Eliminating bullying at work may be an important contribution to the prevention of MDE. PMID- 22298127 TI - The inconsistency of inconsistency scales: a comparison of two widely used measures. AB - This study compared the inconsistent responding validity scales of the Personality Assessment Inventory (PAI) and the Psychopathic Personality Inventory (PPI)/PPI-Revised (PPI-R) in two correctional samples to determine the extent to which they overlap in identifying invalid profiles. Results revealed substantial differences in the way the inconsistent responding validity scales of these measures performed. In particular, the PAI identified far fewer participants as having responded inconsistently compared with the PPI/PPI-R. We discuss the implications of our findings for clinical practice, and potential concerns with the use of a single measure to identify inconsistent responding in clinical practice and research. PMID- 22298128 TI - Obstacles to research in residential juvenile justice facilities: recommendations for researchers. AB - Federal, state, and local initiatives to improve the treatment and outcomes for young people in the juvenile justice system prompt the need for additional research. Despite the call for empirical data, researchers encounter numerous obstacles when initiating and conducting studies in detention and post adjudication facilities. These obstacles are often only briefly mentioned in publications, but they can interfere with researchers' desires and abilities to conduct studies in these settings. This paper reviews legal, ethical, and methodological challenges to successfully conducting research in detention and residential post-adjudication placements, including selecting and accessing appropriate facilities, obtaining institutional review board approval, seeking parental permission and youth assent, reporting child abuse and neglect, responding to participants' threats to harm self or others, working effectively with facilities, juvenile justice system-related attrition, and the dissemination of research findings. Recommendations are presented to help investigators anticipate obstacles when designing and executing research protocols to prevent interference and to encourage ethical responses and successful study completion. PMID- 22298130 TI - Defining public health. PMID- 22298129 TI - Reversible tuning luminescent color and emission intensity: a dipeptide-based light-emitting material. AB - A smart luminescent material whose emission color and emission intensity can be separately modulated by external force is demonstrated. The rational manipulation of rich noncovalent interactions and fluorophore packing style promotes an in depth understanding between supramolecular structure and photophysical property and offers an effective strategy to modulate the light-emitting property in a predicative way. PMID- 22298132 TI - Women's health: beyond reproductive years. AB - With changing demographic profile India has more older women than men as life expectancy for women is 67.57 as against 65.46 for men. Gender differences in the aging process reflect biological, economic, and social differences. Both social and health needs of the older women are unique and distinctive as they are vulnerable. The social problems revolve around widowhood, dependency, illiteracy and lack of awareness about the policies and programmes from which they can benefit. Among the medical problems, vision (cataract) and degenerative joint disease top the list, followed by neurological problems. Lifestyle diseases form another single-most important group of health problems in the elderly women. The risk of cardiovascular disease doubles with the outcome being poorer than men. The most common causes of death among women above the age of 60 years are stroke, ischemic heart disease and COPD. Hypertensive heart disease and lower respiratory tract infections contribute to mortality in these women. Common malignancies viz. Cervical, breast and uterus in women are specific to them and account for a sizeable morbidity and mortality. In a study done at Lady Hardinge medical college in Delhi, Hypertension (39.6%) and obesity (12-46.8%) were very common in postmenopausal women. Half or more women had high salt and fat intake, low fruit and vegetable intake and stress. There is a need to recognize the special health needs of the women beyond the reproductive age, to be met through strengthening and reorienting the public health services at all levels starting from primary health care to secondary till tertiary care level with adequate referral linkages. All policies and programs need to have a gender perspective. At present there is lack of sensitization and appropriate training of the health personnel in dealing with the needs of elderly. Women too need to be aware to adopt healthy lifestyle and seek timely care. PMID- 22298133 TI - Determinants of utilization of services under MMJSSA scheme in Jharkhand 'Client Perspective': a qualitative study in a low performing state of India. AB - Preventing maternal death associated with pregnancy and child birth is one of the greatest challenges for India. Approximately 55,000 women die in India due to pregnancy- and childbirth- related conditions each year. Increasing the coverage of maternal and newborn interventions is essential if Millennium Development Goals (MDG) 4 and 5 are to be reached. With a view to accelerate the reduction in maternal and neonatal mortality through institutional deliveries, Government of India initiated a scheme in 2005 called Janani Suraksha Yojna (JSY) under its National Rural Health Mission (NRHM). In Jharkhand the scheme is called the Mukhya Mantri Janani Shishu Swasthya Abhiyan (MMJSSA). This paper focuses on community perspectives, for indentifying key areas that require improvement for proper implementation of the MMJSSA in Jharkhand. Qualitative research method was used to collect data through in-depth interviews (IDIs) and focus group discussions (FGDs) in six districts of Jharkhand- Gumla, West Singhbhum, Koderma, Deoghar, Garhwa, and Ranchi. Total 300 IDIs (24 IDIs each from mother given birth at home and institution respectively; two IDIs each with members of Village Health and Sanitation Committees (VHSC) / Rogi Kalyan Samitis (RKS) from each district) and 24 FGDs (four FGDs were conducted from pools of husbands, mothers in-law and fathers-in-law in each district) were conducted. Although people indicated willingness for institutional deliveries (generally perceived to be safe deliveries), several barriers emerged as critical obstacles. These included poor infrastructure, lack of quality of care, difficulties while availing incentives, corruption in disbursement of incentives, behavior of the healthcare personnel and lack of information about MMJSSA. Poor (and expensive) transport facilities and difficult terrain made geographical access difficult. The level of utilization of maternal healthcare among women in Jharkhand is low. There was an overwhelming demand for energizing sub-centers (including for deliveries) in order to increase access to maternal and child health services. Having second ANMs will go a long way in achieving this end. The MMJSSA scheme will thus have to re-invent itself within the overall framework of the NRHM. PMID- 22298134 TI - Assessing Indian public health standards for community health centers: a case study with special reference to essential newborn care services. AB - The main objective of the study is to identify the availability of infrastructure facility, human resources, investigative services, and facility based newborn care services with respect to Indian Public Health Standards (IPHS) at community health centers (CHC) of Bharatpur District of Rajasthan State. Data were collected from service providers at CHC through well structured questionnaire at thirteen CHCs situated at Bharatpur District of Rajasthan State. It was found that infrastructure facilities were available in almost all the CHCs, but shortage of manpower especially specialists was observed. Availability of investigative services was found quite satisfactory except ECG. It was also observed that none of the CHCs have fully equipped facility based newborn care services (including newborn corner and newborn care stabilization unit). As per IPHS suggested in the revised draft (2010) important deficiencies were revealed in the studied CHCs of Bharatpur district and by additional inputs such as recruiting staff, improving infrastructure facilities, CHCs can be upgraded. PMID- 22298135 TI - Typhoid vaccine: a case for inclusion in national program. AB - Typhoid has been reported to be a common and significant cause of morbidity in pre-school and school-age children in the endemic countries like India. The incidence of typhoid has been reported to be as high as 27.3 per 1000 person years in children less than 5 years of age. Serious complications occur in about 10% of cases requiring hospitalization. The mean cost of treatment per episode of blood culture-confirmed typhoid fever has been calculated as INR 3,597 (1996 prices) in an outdoor setting, whereas in case of hospitalization, the cost of illness increases by several folds (INR 18,131). Vi polysaccharide vaccine is safe, efficacious and affordable for use as a cost-effective public health tool to protect children from typhoid and related complications, when given at 2 and 5 years of age as a part of National Immunization Schedule. PMID- 22298136 TI - Human development report 2010: Changes in parameters and perspectives. AB - Human Development Report (HDR) 2010 in its 20 th year contains several significant changes. Indicators to measure the three dimensions of Human Development Index (HDI) have been changed: Gender-related Development Index (GDI) and Gender Empowerment Index have been replaced by Gender Inequality Index (GII) and Human Poverty Index has been replaced by Multi-dimensional Poverty Index. Inequality-adjusted HDI (IHDI) has been introduced for the first time. Between 1980 and 2010, India's HDI rose by 1.6% annually from 0.320 to 0.519. While India's HDI value has improved over time, the rank has not improved as much as compared to other developing countries. On GII, India ranked at 122 with a GII value of 0.748 (ranges between 0 and 1) in 2010 HDR (based on data of 2008), revealing considerable loss in achievements in three dimensions of human development - reproductive health, empowerment, and labor market - due to inequality between genders. Multi-dimensional Poverty Index was 0.296 (2000-2008) and IHDI was 0.365 (2000-2007). PMID- 22298137 TI - Evidence based communication for health promotion: Indian lessons of last decade. AB - Good health promotion programs which help achieve public health goals are derived from using a mix of epidemiological and social and behavioral science research information. Social data informed by behavioral theories provides a lens of understanding how recommended behaviors are adopted by different individuals within the population over a period of time. In addition to social and epidemiological data, evidence based and scientifically planned and monitored strategic communication interventions have to be linked to available service components of the program. Communication is increasingly understood as an enabler of individual and social level change to achieve established developmental goals including health. Democratization movements and the advent of the internet have changed the environment around any program communication from top-down, expert-to consumer (vertical) communication towards non-hierarchical, dialogue-based (horizontal) communication, through which the public increasingly questions recommendations of experts and public institutions on the basis of their own, often web based, research. The amount of information available has increased greatly, including scientifically valid data and evidence-based recommendations alongside poor quality data, personal opinions, and misinformation. Evidence based approaches include engagement with and listening to stakeholders, and being transparent about decision making, and honest and open about uncertainty and risks. Decision and policy makers cannot assume what the public wants without undertaking social science and decision science research. The Global Polio Eradication Initiative and Integrated Disease Surveillance Projects (IDSP) in India haves shown that monitoring of public concerns needs to be continuous and responsive, and hand in hand with the monitoring of technical strategies and appropriate Information Technology support for, not only data transmission but also for videoconferencing and community involvement through toll free 24 * 7 call service with universal access. This article elucidates the vital role of Health Promotion, a research based communication process, in achieving developmental, particularly health goals. It underscores that communication is as much a science as an art, as much process as it is about outcomes. It advocates for increased linkages between epidemiological research and social science research in planning effective health promotion interventions with quality service delivery. PMID- 22298138 TI - A study on prevalence of bacteria in the hands of children and their perception on hand washing in two schools of Bangalore and Kolkata. AB - BACKGROUND: Contaminated hands play a major role in fecal-oral transmission of diseases. In 1847, Dr Semmelweis Ignac pointed to the link between infection and unclean hands, and demonstrated that washing hands could reduce transmission of puerperal fever (child birth fever), a dreaded disease with high mortality in those days. MATERIALS AND METHODS: A cross-sectional study was conducted to find out the extent of germs present in hand, and also the students' perception on hand washing. This was assessed by questionnaire as well as by collection of swab from hand and performing bacteriological culture in the laboratory. RESULTS: In regard to students' perception about the dirty areas of the hands, it was observed that majority (78%) felt palm was likely to be more dirty while less than 70% felt that web spaces could harbor dirt. Almost 86% reported that they washed hands before eating lunch, but only 21.3% said they always used soap while 47.3% never used it. Availability of soap all the time in the school was reported by only 18.4% students. The swabs of 61% children showed potential pathogens. The commonest of these was Staphylococcus aureus which was seen in 44% samples. CONCLUSION: The students' hands were contaminated before taking food. Although they washed hands before meals, they hardly used soap due to non-availability of soap. The school authority should be asked to keep soaps in the toilets for hand washing. PMID- 22298139 TI - Knowledge and skills of primary health care workers trained on integrated management of neonatal and childhood illness: follow-up assessment 3 years after the training. AB - BACKGROUND: The primary health care workers of a district in northern India were trained in the year 2006 for Integrated Management of Neonatal and Childhood Illness (IMNCI) using two different training methods: conventional 8-day training and new interrupted 5-day training. Knowledge and skills may decline over a period of time. Rate of decline may be associated with the type of training. A study was thus conducted to see the retention of knowledge and skills in the two training groups, 3 years after the initial training. MATERIALS AND METHODS: This study was done in the Panchkula district of Haryana state in northern India. In the year 2006, 50 primary health care workers were given new interrupted 5-day training and another 35 workers were given conventional 8-day training on IMNCI. Knowledge and skills of the same workers were evaluated in the year 2009, using the same methodology and tools as were used in the year 2006. Data analysis was done to see the extent of decline in knowledge and skills in these 3 years and whether decline was more in any particular training group. RESULTS: Compared to post-training score in the year 2006, composite knowledge and skill scores for Auxilliary Nurse Midwives (ANMs) and Anganwari workers (AWWs) together declined significantly in the year 2009 from 74.6 to 58.0 in 8-day training group and from 73.2 to 57.0 in 5-day training group (P < 0.001). Follow-up composite scores in the two training groups were similar. Whereas the decline was more for knowledge scores in 8-day training group and for skill score in 5-day training group, the pattern of decline was inconsistent for different health conditions and among ANMs and AWWs. CONCLUSION: Long-term retention of knowledge and skills in 5-day group was equivalent to that in 8-day training group. Refresher trainings may boost up the decline in the knowledge and skills. PMID- 22298140 TI - Health impact of supplying safe drinking water containing fluoride below permissible level on flourosis patients in a fluoride-endemic rural area of West Bengal. AB - BACKGROUND: The problem of high fluoride concentration in groundwater resources has become one of the most important toxicological and geo-environmental issues in India. Excessive fluoride in drinking water causes dental and skeletal fluorosis, which is encountered in endemic proportions in several parts of the world. World Health Organization (WHO) guideline value and the permissible limit of fluoride as per Bureau of Indian Standard (BIS) is 1.5 mg/L. About 20 states of India, including 43 blocks of seven districts of West Bengal, were identified as endemic for fluorosis and about 66 million people in these regions are at risk of fluoride contamination. Studies showed that withdrawal of sources identified for fluoride often leads reduction of fluoride in the body fluids (re-testing urine and serum after a week or 10 days) and results in the disappearance of non skeletal fluorosis within a short duration of 10-15 days. OBJECTIVE: To determine the prevalence of signs and symptoms of suspected dental, skeletal, and non skeletal fluorosis, along with food habits, addictions, and use of fluoride containing toothpaste among participants taking water with fluoride concentration above the permissible limit, and to assess the changes in clinical manifestations of the above participants after they started consuming safe drinking water. MATERIALS AND METHODS: A longitudinal intervention study was conducted in three villages in Rampurhat Block I of Birbhum district of West Bengal to assess the occurrence of various dental, skeletal, and non-skeletal manifestations of fluorosis, along with food habits, addictions, and use of fluoride containing toothpaste among the study population and the impact of taking safe water from the supplied domestic and community filters on these clinical manifestations. The impact was studied by follow-up examination of the participants for 5 months to determine the changes in clinical manifestations of the above participants after they started consuming safe drinking water from supplied domestic filters and community filter with fluoride concentration below the permissible limit. The data obtained were compared with the collected data from the baseline survey. RESULTS: The prevalence of signs of dental, skeletal, and non-skeletal fluorosis was 66.7%, 4.8-23.8%, and 9.5-38.1%, respectively, among the study population. Withdrawal of source(s) identified for fluoride by providing domestic and community filters supplying safe water led to 9.6% decrease in manifestation of dental fluorosis, 2.4-14.3% decrease in various manifestations of skeletal fluorosis, and 7.1-21.5% decrease in various non-skeletal manifestations within 5 months. Following repeated motivation of participants during visit, there was also 9.7-38.1% decrease in the usage of fluoride containing toothpaste, and 9.8 45.3% and 7.3-11.9% decrease in the consumption of black lemon tea and tobacco, respectively, which are known sources of fluoride ingestion in our body and have an effect on the occurrence of various manifestations of fluorosis following drinking of safe water from domestic and community filters. CONCLUSION: Increased prevalence of dental, skeletal, and non-skeletal fluorosis was found among the study population. Withdrawal of source(s) identified for fluoride by supplying domestic and community filters, dietary restriction, and other nutritional interventions led to decrease in manifestation of the three types of fluorosis within 5 months. PMID- 22298141 TI - Provocative poliomyelitis causing postpolio residual paralysis among select communities of two remote villages of North Karnataka in India: a community survey. AB - Intramuscular injections can provoke muscular paralysis especially, if the child has had exposure to polio virus. The purpose of the study was to determine the association with known risk factors for motor disabilities in two remote villages of North Karnataka (India), where an increased number of disabled people among select communities had been reported. A community based survey was conducted. The selection of study subjects was done through screening, history related with occurrence of musculoskeletal disability, screening and general examination of the affected joints and muscles. Data analysis was done by estimation of percentages. Among the physical disabilities identified, the most common was post polio residual paralysis. 35.65% (n = 41) subjects had developed paralysis following the administration of an intramuscular injection when they had acute viremia in childhood, indicating that (probably) muscle paralysis would have been provoked by intramuscular injections, resulting in provocative poliomyelitis. Unnecessary injection must be avoided in children during acute viremia state and use of oral polio vaccine should be encouraged. PMID- 22298142 TI - A clinico-epidemiological study of Chikungunya outbreak in Maharashtra State, India. AB - The year 2006 witnessed an extensive outbreak of Chikungunya fever in Maharashtra state. Out of 6467 sera of suspected patients sent to National Institute of Virology, Pune, 804 were serologically confirmed. This retrospective study was carried out by interrogating all those patients for their sickness experience. Adult females from rural area were more affected than males. In 68.2% families, there were multiple cases. Fever and multiple joint involvement were almost invariable. In 36.5% patients, there was history of recurrence. Along with pain, slight swelling was noticed in 55% patients. The commonest joints involved were wrist, inter-phalangeal, elbow, knee and ankle, in that order. The pain and swelling persisted for more than a month. After health education during outbreak, there was positive improvement in behavior pertaining to source reduction of vector. Inter-personal communication was best remembered. In health education, the role of paramedical workers and government doctors was prominent. PMID- 22298143 TI - Nutritional anemia and its epidemiological correlates among women of reproductive age in an urban slum of Bhubaneswar, Orissa. AB - The present cross-sectional study involving 240 women of reproductive age as the study population was carried out in the beneficiary slum area, the field practice area of Community Medicine department to find out the burden of nutritional anemia and study its epidemiological correlates. The prevalence of anemia was found to be 60.8%, of which 39.6, 20.0 and 1.2% women had mild, moderate and severe anemia, respectively. Almost 63, 21.2 and 15.7% of the study subjects had microcytic hypochromic picture, indicative of iron deficiency anemia, normocytic hypochromic picture suggestive of early stage of iron deficiency anemia and dimorphic/ macrocytic hypochromic anemia implying iron deficiency anemia and or folate/vitamin B12 deficiency respectively. Statistical analyses have shown that epidemiological factors like age, education of respondents, socioeconomic status, history of excessive menstrual bleeding and inadequate intake of green leafy vegetables and pulses were found to be significantly associated with anemia. PMID- 22298144 TI - Why infants miss vaccination during routine immunization sessions? Study in a rural area of Anand District, Gujarat. AB - A cross-sectional study was conducted in a rural area of Anand District, Gujarat to measure the efficiency of immunization sessions and to identify the reasons for missing a vaccine in a session. Caregivers of infants aged less than one year and in need of any vaccine as per routine immunization schedule were interviewed by a house-to-house survey after immunization session was completed. Efficiency of immunization session was 66.7%. Reasons for 'missed' vaccination were prior reminder not given (32.9%, P<0.01); mother's forgetfulness (26.6%); unavailability of vaccine (15%). Higher birth order (OR=2.86; 3.16-2.56), mother's current residence at father's home (OR=3.17; 3.53-2.81) were associated with 'missed' vaccination. There are barriers in health care system such as lack of prior reminder and unavailability of vaccines which should be assessed and eliminated. PMID- 22298145 TI - Study comparing the management decisions by IMNCI algorithm and pediatricians in a teaching hospital for the young infants between 0 to 2 months. AB - Integrated management of neonatal and childhood illness (IMNCI) was already operational in many states of India, but there were very few studies in Indian scenario comparing its validity and reliability with the decisions of pediatricians. The general objective of the study is to compare the IMNCI decisions with the decisions of pediatricians and the specific objectives are to assess the agreement between IMNCI decisions and the decisions of pediatricians, to assess the under diagnosis and over diagnosis in IMNCI algorithm in comparison to the decisions of pediatricians and to assess the significance of multiple presenting symptoms in IMNCI algorithm. The study was conducted among the sick young infants presenting in pediatric department from January to March 2009. The IMNCI decision was compared with pediatrician's decisions by percent agreement, Kappa and weighted Kappa with the aids of SPSS version 10. The overall diagnostic agreement between IMNCI algorithm and pediatrician's decisions was 55.56%, (Kappa 0.32 and weighted Kappa 0.41) with 33.33% over diagnosis, and 11.11% under diagnosis. 71.88% young infants with multiple symptoms and 40% with single symptom were classified as red by IMNCI algorithm, which is statistically significant (P=0.004) whereas 56.25% young infants with multiple and 31.76% with single symptom were considered admissible by pediatricians, which is not statistically significant (P=0.052). PMID- 22298146 TI - Pulmonary tuberculosis among HIV seropositives attending a counseling center in Kolkata. AB - The study was carried out to detect the prevalence of pulmonary tuberculosis among HIV-seropositive individuals (HIV/TB co-infection) who attended counseling center of National Institute of Cholera and Enteric Diseases, Kolkata. A total of 109 HIV-seropositive individuals were screened. Of them, 36 (33%) had HIV/TB co infection diagnosed by chest X-ray and presence of acid fast bacillus (AFB) detected by repeated microscopic examination of sputum. Blood samples were examined for CD4 and CD8 counts and ratio. Findings of blood examination showed that low CD4 count (<50/MUl) had statistically significant association (P = 0.007) with HIV/TB co-infection as compared to HIV infection only. However, no significant correlation with CD4:CD8 ratio in HIV/TB co-infection was observed. PMID- 22298147 TI - A study on the role of parental involvement in control of nutritional anemia among children of free primary schools in a rural area of West Bengal. AB - An intervention study was conducted among students of three randomly selected free primary schools in rural West Bengal to assess the effect of health nutrition education for behavior modification of parents on nutritional anemia of children. Clinically anemic students were school-wise randomized into 'groups of two' and intervened with anthelminthic, iron-folic acid (IFA) pediatric tablet and health-nutrition education by reoriented teachers. Parents of study group were involved in behavior change processes. Baseline overall prevalence of anemia was 64.4%. After IFA therapy, prevalence of anemia was not found to differ between two groups (chi2 = 2.68, P > 0.05, RR= 0.48, 95% C.I 0.2 < RR < 1.19) while reducing 52.2% of relative risk. Reassessment after six months showed significantly lower prevalence in study group (chi2 = 18.14, P < 0.05, RR = 0.20, 95% C.I. 0.08 < RR < 0.49). Parental involvement for life style and dietary modification may curb childhood anemia. PMID- 22298148 TI - What is the current trend in public private partnership toward the welfare of the disabled in the state of Goa? PMID- 22298149 TI - Evaluation of parasites causing gastro-intestinal tract infestations in HIV/AIDS patients. PMID- 22298150 TI - Knowledge, attitude and practices regarding anti-tobacco measures among members of Panchayati Raj Institutions in a rural area of Haryana. PMID- 22298151 TI - Perception of accredited social health activists regarding oral health in Northern India. PMID- 22298152 TI - Author response: Bayesian estimation of sensitivity of temporal artery biopsies. PMID- 22298153 TI - Critical difference applied to exercise-induced oxidative stress: the dilemma of distinguishing biological from statistical change. AB - Even though intense exercise has traditionally been associated with a statistically significant accumulation of blood-borne biomarkers of free radical mediated lipid peroxidation, it remains to be determined if the oxidative stress response is biologically significant. To examine biological significance, we calculated the critical difference of selected biomarkers of oxidants antioxidants in the peripheral circulation of ten male subjects aged 24+/-3 years. Venous blood was drawn in the resting supine position every hour over an 8 h period (Study 1). As proof-of-concept, supine venous blood was also obtained at rest and following maximal cycling exercise in a separate group of 13 males, mean age 22+/-3 years (Study 2). The critical difference of electron paramagnetic resonance spin-trapped alkoxyl free radicals, lipid hydroperoxides, malondialdehyde, ascorbic acid, retinol, lycopene, alpha-tocopherol, beta carotene and alpha-carotene was calculated as 121%, 28%, 50%, 9%, 29%, 106%, 13%, 28% and 107%, respectively (Study 1). Maximal exercise was associated with a statistically significant (P<0.05 vs. rest) reduction in alpha-tocopherol and retinol, and a corresponding rise in alkoxyl free radicals and lipid hydroperoxides (Study 2). However, these changes were all within the critical difference percentage value. In conclusion, these findings highlight the importance of distinguishing biological from statistical significance when assessing the physiological and clinical impact of exercise-induced oxidative stress. PMID- 22298154 TI - Pectus excavatum: echocardiography and cardiac MRI reveal frequent pericardial effusion and right-sided heart anomalies. AB - AIMS: In patients with pectus excavatum (PEX), echocardiographic assessment can be difficult. There are little data on the impact of the chest deformity on echocardiographic findings and comparison of data obtained by echocardiography (echo) with cardiac magnetic resonance imaging (CMR) in PEX. METHODS AND RESULTS: In a prospective study, cardiac anomalies in PEX were analysed by echo and compared with CMR in consecutive patients with PEX referred for echo. If they agreed to participate, the patients were referred for CMR and included if the pectus index was >=3.0 by CMR. Also, clinical data and electrocardiogram tracings were analysed. There were 18 patients (13 females; 72%), with a mean age of 53+/ 16 years; mean pectus index was 4.7 (range: 3-7.3). Echo showed haemodynamically insignificant pericardial effusion in six patients (33%), tricuspid valve prolapse in five (28%), right ventricular (RV) localized wall motion anomalies (WMA) in five (28%) and diminished RV systolic function in two (11%); no patient had RV dilatation. CMR demonstrated cardiac displacement to the left in 9 patients (50%); minimal pericardial effusion was seen in 10 patients (56%; P value=0.13 compared with echo), RV localized WMA in 6 (44%; P value=1.0), diminished RV systolic function in 8 (44%; P=0.07), and RV dilatation in 5 (28%; P=0.06). A completely normal cardiac examination was found in six patients by echo (33%) and in 2 (11%) using CMR. Although some signs of arrhythmogenic RV cardiomyopathy (ARVC) were present, no patient fulfilled the ARVC criteria. CONCLUSION: In severe PEX, haemodynamically insignificant pericardial effusion, tricuspid valve prolapse and other RV anomalies possibly due to RV displacement are frequent as demonstrated by both CMR and echo. The cardiac assessment by echo and CMR did show discrepancies; however, they were not significant. PMID- 22298155 TI - Letter by Daniels Regarding Article "Silent Aspiration Risk is Volume-Dependent" PMID- 22298156 TI - First-principles molecular dynamics simulations of condensed-phase V-type nerve agent reaction pathways and energy barriers. AB - Computational studies of condensed-phase chemical reactions are challenging in part because of complexities in understanding the effects of the solvent environment on the reacting chemical species. Such studies are further complicated due to the demanding computational resources required to implement high-level ab initio quantum chemical methods when considering the solvent explicitly. Here, we use first-principles molecular dynamics simulations to examine condensed-phase decontamination reactions of V-type nerve agents in an explicit aqueous solvent. Our results include a detailed study of hydrolysis, base-hydrolysis, and nucleophilic oxidation of both VX and R-VX, as well as their protonated counterparts (i.e., VXH(+) and R-VXH(+)). The decontamination mechanisms and chemical reaction energy barriers, as determined from our simulations, are found to be in good agreement with experiment. The results demonstrate the applicability of using such simulations to assist in understanding new decontamination technologies or other applications that require computational screening of condensed-phase chemical reaction mechanisms. PMID- 22298157 TI - Pelvic Inflammatory Disease: Current Concepts of Diagnosis and Management. AB - Pelvic inflammatory disease (PID), one of the most common infections in non pregnant women of reproductive age, remains an important public health problem. It is associated with major long-term sequelae, including tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. In addition, treatment of acute PID and its complications incurs substantial health care costs. Prevention of these long-term sequelae is dependent upon clinicians having a high index of suspicion in order to make an early diagnosis and development of treatment strategies based on knowledge of the microbiologic etiology of acute PID. It is well accepted that acute PID is a polymicrobic infection. The sexually transmitted organisms, Neisseria gonorrhoeae and Chlamydia trachomatis, are present in many cases and microorganisms comprising the endogenous vaginal and cervical flora are frequently associated with PID. This includes anaerobic and facultative bacteria, similar to those associated with bacterial vaginosis. Genital tract mycoplasmas, most importantly Mycoplasma genitalium, have recently also been implicated as a cause of acute PID. As a consequence, treatment regimens for acute PID should provide broad spectrum coverage that is effective against these microorganisms. PMID- 22298158 TI - Activated graphene as a cathode material for Li-ion hybrid supercapacitors. AB - Chemically activated graphene ('activated microwave expanded graphite oxide', a MEGO) was used as a cathode material for Li-ion hybrid supercapacitors. The performance of a-MEGO was first verified with Li-ion electrolyte in a symmetrical supercapacitor cell. Hybrid supercapacitors were then constructed with a-MEGO as the cathode and with either graphite or Li(4)Ti(5)O(12) (LTO) for the anode materials. The results show that the activated graphene material works well in a symmetrical cell with the Li-ion electrolyte with specific capacitances as high as 182 F g(-1). In a full a-MEGO/graphite hybrid cell, specific capacitances as high as 266 F g(-1) for the active materials at operating potentials of 4 V yielded gravimetric energy densities for a packaged cell of 53.2 W h kg(-1). PMID- 22298159 TI - Rational aspect ratio and suitable antibody coverage of gold nanorod for ultra sensitive detection of a cancer biomarker. AB - We report a simple, ultra-sensitive, and straightforward method for non-labeling detection of a cancer biomarker, using Rayleigh light scattering spectroscopy of the individual nanosensor based on antibody-antigen recognition and localized surface plasmon resonance (LSPR) lambda(max) shifts. By experimentally measuring the refractive index sensitivity of Au nanorods, the Au nanorod with an aspect ratio of ~3.5 was proven optimal for the LSPR sensing. To reduce the steric hindrance effect as well as to immobilize a large amount of ligand on the nanoparticle surface, various mixtures containing different molar ratios of HS(CH(2))(11)(OCH(2)CH(2))(6)OCH(2)COOH and HS(CH(2))(11)(OCH(2)CH(2))(3)OH were applied to form different self-assembled monolayer surfaces. The results showed that the best molar ratio for antibody conjugation was 1 : 10. When using individual Au nanorod sensors for the detection of prostate specific antigen (PSA), the lowest concentration recorded was ~1 aM (~6 * 10(5) molecules), corresponding to LSPR lambda(max) shifts of ~4.2 nm. These results indicate that sensor miniaturization down to the nanoscale level, the reduction of steric hindrance, and optimization of size, shape, and aspect ratio of nanorods have led to a significant improvement in the detection limit of sensors. PMID- 22298160 TI - Venous thrombosis following femoral venous access for electrophysiology studies: an on-going challenge. PMID- 22298161 TI - ARISTOTLE RE-LYs on the ROCKET. What's new in stroke prevention in patients with atrial fibrillation? AB - Warfarin has long been considered the gold standard for stroke prevention in patients with atrial fibrillation (AF). Recently, three major trials comparing the efficacy and safety of new drugs: a thrombin inhibitor dabigatran and two inhibitors of factor Xa - rivaroxaban and apixaban, with that of warfarin, have been published. The aim of this paper is to present the main results of the RE LY, ROCKET AF and ARISTOTLE trials, compare study populations and outcomes, and discuss clinical implications of their results for the long-term anticoagulation in patients with nonvalvular AF. PMID- 22298162 TI - The advent of cardiac resynchronization therapy has created a confusing terminology of heart failure. PMID- 22298163 TI - Predictors of local venous complications resulting from electrophysiological procedures. AB - BACKGROUND: Thromboembolic complications resulting from radiofrequency catheter ablation (RFCA) have an overall incidence of 0.6%. Multiple intracardiac catheters are often necessary for electrophysiological study and RFCA therapy. Therefore, the placement of multiple venous sheaths in one femoral vein is always required for multiple intracardiac catheter insertion. The safety of the placement of multiple separate venous sheaths has been studied previously in a non-randomized study, but the placement of multiple sheaths via one venous line has not been fully studied. METHODS AND RESULTS: A randomized clinical trial was conducted with a total of 200 patients. We studied the safety of placing multiple sheaths via one venous line, and the effect of heparin on deep vein thrombosis (DVT) and on in situ thrombosis. DVT was not seen in our patients. We observed a significant decrease in the rate of in situ thrombosis in patients who received heparin during the procedure (28% vs 11%, p = 0.04). The type of cannulation changed the in situ thrombosis rate independently of the heparinization protocol. The rate of in situ thrombosis was higher when placing sheaths via one venous line regardless of the heparinization protocol used (16% vs 6%, p = 0.1 for the group on heparin, and 38% vs 18%, p = 0.04 for the other group). In the group cannulated with only one venous line (100 patients), heparinization significantly decreased the rate of in situ thrombosis (16% vs 38%, p = 0.023), but there was an insignificant decrease in the separate cannulation group (6% vs 18%, p = 0.12). Advanced age had no effect on thrombosis. Surprisingly, there was a significantly greater rate of in situ thrombosis (not DVT) among women than among men (26% vs 11%, p = 0.01), regardless of the heparinization protocolor the type of cannulation. CONCLUSIONS: Given the local venous complications and DVT after electrophysiological procedures, heparinization is not necessary for right-sided electrophysiological procedures. In situ thrombosis is a minor complication that can be reduced by heparinization in patients undergoing one-line cannulation and in women during longer procedures. PMID- 22298164 TI - Simvastatin and atorvastatin attenuate VCAM-1 and uPAR expression on human endothelial cells and platelet surface expression of CD40 ligand. AB - BACKGROUND: In addition to their cholesterol lowering ability, statins have proven pleiotropic effects in the cardiovascular system. Chronic inflammation with interactions between platelets and endothelial cells leads to an upregulation of activity markers of atherosclerosis. The purpose of this study was to investigate the effects of simvastatin and atorvastatin on platelets and endothelial cells in an in vitro endothelial cell model. METHODS AND RESULTS: After a 24 h incubation period with either simvastatin or atorvastatin (1 MUmol/L), human umbilical vein endothelial cells were stimulated for 1 h with lipopolysaccharide (LPS), and were then incubated in direct contact with activated platelets. Platelet surface expression of CD40L and CD62P and expression of ICAM-1, VCAM-1, uPAR and MT1-MMP on endothelial cells were measured by flow cytometry. Supernatants were analyzed by ELISA for soluble MMP-1. The increased expression of VCAM-1 and uPAR on endothelial cells by stimulation with LPS and by direct contact with activated platelets was significantly reduced to a similar extent through pre-incubation with both atorvastatin and simvastatin (p < 0.05). Platelets without endothelial cell contact, but in direct contact with either statin, showed similar significant reductions in surface expression of CD40L (p < 0.005). CONCLUSIONS: These effects may explain the ability of statins to reduce the progression of atherosclerosis in addition to their cholesterol lowering properties. PMID- 22298165 TI - The relationship between L-arginine/ADMA ratio and coronary collateral development in patients with low glomerular filtration rate. AB - BACKGROUND: It is yet to be established which factors are responsible for differences among patients with the same degree of coronary artery disease in terms of coronary collateral development (CCD). METHODS: Patients who had a greater than or equal to 95% stenosis in at least one epicardial coronary artery were classified into two groups according to their glomerular filtration rate (GFR) level. Afterwards, the degree of CCD was evaluated according to their plasma concentration of asymmetric dimethylarginine (ADMA) and GFR levels. RESULTS: Rentrop grade 2-3 was found more frequently in patients with GFR > 60 mL/min than in patients with GFR < 60 mL/min (68.6% vs 41.4%, p = 0.032). Then we divided patients into four groups according to their GFR levels and Rentrop grades; whereas we did not find any significant difference for L-arginine or ADMA levels (respectively p = 0.629 and p = 0.076), we did find a statistically significant difference between groups for L-arginine/ /ADMA ratio (p = 0.003) and this statistically significant difference was evident between patients with GFR < 60 mL/min and Rentrop 0-1 and patients with GFR > 60 mL/min and Rentrop 2-3 (1.23 vs 1.69, p < 0.001). Multivariate logistic regression analysis revealed that L arginine/ADMA ratio was the only variable which had a significant effect on CCD (OR = 1.016; 95% CI 1.001-1.031, Wald = 4.565; p = 0.033). CONCLUSIONS: These results showed that CCD was poor in patients with GFR < 60 mL/min, presumably because of the adverse effect of decreased L-arginine/ADMA ratio on endothelial cells and angiogenesis. PMID- 22298166 TI - Severe chronic heart failure in patients considered for heart transplantation in Poland. AB - BACKGROUND: Based on the results of clinical trials, the prognosis for patients with severe heart failure (HF) has improved over the last 20 years. However, clinical trials do not reflect 'real life' due to patient selection. Thus, the aim of the POLKARD-HF registry was the analysis of survival of patients with refractory HF referred for orthotopic heart transplantation (OHT). METHODS: Between 1 November 2003 and 31 October 2007, 983 patients with severe HF, referred for OHT in Poland, were included into the registry. All patients underwent routine clinical and hemodynamic evaluation, with NT-proBNP and hsCRP assessment. Death or an emergency OHT were assumed as the endpoints. The average observation period was 601 days. Kaplan-Meier curves with log-rank and univariate together with multifactor Cox regression model the stepwise variable selection method were used to determine the predictive value of analyzed variables. RESULTS: Among the 983 patients, the probability of surviving for one year was approximately 80%, for two years 70%, and for three years 67%. Etiology of the HF did not significantly influence the prognosis. The patients in NYHA class IV had a three-fold higher risk of death or emergency OHT. The univariate/multifactor Cox regression analysis revealed that NYHA IV class (HR 2.578, p < 0.0001), HFSS score (HR 2.572, p < 0.0001) and NT-proBNP plasma level (HR 1.600, p = 0.0200), proved to influence survival without death or emergency OHT. CONCLUSIONS: Despite optimal treatment, the prognosis for patients with refractory HF is still not good. NYHA class IV, NT-proBNP and HFSS score can help define the highest risk group. The results are consistent with the prognosis of patients enrolled into the randomized trials. PMID- 22298167 TI - Aging reduces left atrial performance during adrenergic stress in middle aged and older patients. AB - BACKGROUND: During adrenergic stress, the influence of age on left atrial (LA) function is unknown. We hypothesized that aging decreases LA total emptying fraction (LAEF) during maximal adrenergic stress. The aim of the study was to determine the influence of aging on LA function during adrenergic stress in middle aged and older patients. METHODS: We enrolled 167 middle aged and elderly participants, and measured LA and left ventricular (LV) volumes using a multi slice three-dimensional cine white blood cardiovascular magnetic resonance (CMR) technique before and during intravenous dobutamine infused to achieve 80% of the maximum heart rate response for age. Paired sample t-test was used to detect differences in LA and LV volumes between baseline and peak dose stage of dobutamine stress CMR, and multivariable linear regression was used to identify predictors of LA function. RESULTS: Participants averaged 68 +/- 8 years in age, 53% were men, 25% exhibited coronary artery disease, 35% had diabetes, 9% had a remote history of atrial fibrillation, 90% had hypertension, and 11% had inducible LV wall motion abnormalities indicative of ischemia during dobutamine CMR. Increasing age correlated with LA volumes (maximal and minimal) and inversely correlated with LAEF at rest and after peak adrenergic stress. Age was an independent predictor of LAEF during adrenergic stress, even after accounting for gender, LV volumes, and other co-morbidities including inducible ischemia. CONCLUSIONS: Age is associated with a decrease in LA function during adrenergic stress even after adjusting for co-morbidities associated with cardiovascular disease and LV function. PMID- 22298168 TI - Short-term outcome of early electrical cardioversion for atrial fibrillation in hyperthyroid versus euthyroid patients. AB - BACKGROUND: Atrial fibrillation (AF) is the most common cardiac complication of hyperthyroidism. The influence of the time of cardioversion on hyperthyroidism induced AF remains unclear. The aim of this study was to compare short-term outcomes of early electrical cardioversion for AF in hyperthyroid and euthyroid patients. METHODS AND RESULTS: Sixty-seven subjects with persistent AF (duration, 10 days-12 months) were divided into two groups according to thyroid function: Euthyroid (Group 1, n = 36, female/male: 23/13, mean age: 61.77 +/- 10.45 years) and hyperthyroid (Group 2, n = 31, female/male: 10/21, mean age: 65.43 +/- 6.40 years). Two patients were excluded for unsuccessful cardioversion (one in each group). In Group 2, 19 patients had clinical and 11 had subclinical hyperthyroidism. Following transthoracic and transesophageal echocardiography, cardioversion was performed until the highest energy was reached (270 J) or until sinus rhythm was achieved. AF recurrence was detected in 13 of 35 patients (37.1%) in Group 1 and in 11 of 30 patients (36.9%) in Group 2 (p = 0.96) at one month. Recurrence rate was higher in the clinical hyperthyroid patients than in the subclinical hyperthyroid patients (52.6% vs 9.1%, p = 0.021), but neither the clinical nor the subclinical hyperthyroid subgroups were significantly different from Group 1 in terms of recurrence rate (p = 0.27 and p = 0.13, respectively). CONCLUSIONS: Electrical cardioversion should be performed for patients with persistent AF and hyperthyroidism as soon as possible. PMID- 22298169 TI - ST-segment resolution after primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction. AB - BACKGROUND: The association between ST-segment resolution and clinical outcome in patients with acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PPCI) remains unclear. Recent studies on the association between ST-segment resolution and mortality have given conflicting results. We undertook this study to assess whether ST-segment resolution in electrocardiograms recorded 90-120 min after initiation of PPCI predicts long-term mortality in patients with STEMI. METHODS: The study included 900 patients with STEMI presenting within the first 24 h after symptom onset who were treated with PPCI. The ST-segment resolution was assessed in electrocardiograms recorded 90-120 min after the first balloon inflation. The ST segment resolution was dichotomized as follows: < 30% (no resolution), 30% to <= 70% (partial resolution) and > 70% (complete resolution). The primary endpoint was five-year mortality. RESULTS: ST-segment resolution was < 30% in 263 (29.0%) patients, between 30% and <= 70% in 356 (40.0%) patients and > 70% in 281 (31.0%) patients. There were 62 deaths during the follow-up. In patients with ST-segment resolution < 30%, 30 to <= 70% and > 70%, the Kaplan-Meier estimates of mortality were 8.3% (n = 17 deaths), 11.5% (n = 29 deaths) and 6.8% (n = 16 deaths), respectively; unadjusted hazard ratio (HR) = 0.88, 95% confidence interval (CI) 0.46-1.67, p = 0.695 for ST-segment resolution > 70% vs < 30%; adjusted HR = 0.91, 95% CI 0.61-1.33; p = 0.607, for ST-segment resolution > 70% vs ST-segment resolution < 30%. CONCLUSIONS: In patients with STEMI undergoing PPCI, ST-segment resolution in electrocardiograms recorded 90-120 min after initiation of PPCI did not predict long-term mortality. PMID- 22298170 TI - Evaluation of a direct access cardiac arrhythmia monitoring service. AB - BACKGROUND: This paper describes the clinical outcomes from a novel direct access arrhythmia monitoring service. METHODS: The study was carried out in the north of Scotland. Data was collected over a 29 month period between 18 June 2008 and 8 November 2010 from consecutive cases from two groups of patients, general practitioner (GP) direct access and 'redirected' consultant referrals. Monitor test results, frequency of arrhythmias requiring further care and clinic attendances were recorded. Statistical differences were analyzed using Chi(2), Fisher's and Student's t-test as appropriate with the significance taken at the 0.05 level. RESULTS: 239 patients were referred from 47 GP practices. There were 165 (69%) referrals through the 'direct' and 72 (31%) through the 'redirected' route. The average age was 55.5 +/- 16.7 years with 84 (35.1%) males. 127 (53.1%) had a patient activated event recording and the remaining 112 (46.9%) had Holter monitoring. Of the 239 patients, only nine (3.8%) cases required referral to a consultant cardiologist. Of these, three were directly returned to GP care without consultant clinic review. Six patients with significant arrhythmias were reviewed at cardiology clinic. There were no adverse events. CONCLUSIONS: Direct access for cardiac arrhythmia monitoring seems to provide an effective mechanism for diverting inappropriate or non-essential referrals away from the cardiology clinic. PMID- 22298171 TI - Zolmitriptan-induced acute myocardial infarction. AB - Triptans are an established treatment for acute migraine attacks. By activating 5HT1B/1D receptors they lead to vasoconstriction of the cerebral blood vessels which are dilated during migraine attacks. Moreover, they reduce secretion of vasoactive peptides and conduction of pain stimuli over the cerebral cortex. In up to 7% of cases of treatment with triptans, thoracic pain occurs, although this is mostly transient, mild and without lasting ischemia. We present the case of a 45 year-old woman with a history of migraine with visual aura since the age of 20. She had no history of diabetes mellitus, hypertension, smoking or any other risk factors for cardiovascular events before she was admitted to our emergency room with typical chest pain. An electrocardiogram revealed anterior myocardial infarction following her monthly dose of oral zolmitriptan. Catherization revealed a normal coronary arterial system. The laboratory indices for cardiac risk were within normal ranges. The patient was advised to avoid triptans permanently on being discharged. PMID- 22298172 TI - Progressive bradycardia with increasing doses of dobutamine leading to stress echo interruption. AB - Dobutamine stress testing is an important non-invasive method for evaluating patients with known or suspected coronary artery disease who are unable to adequately exercise. We present a case of a paradoxical, progressive bradycardia occurring with increasing doses of dobutamine that resulted in stress test interruption. PMID- 22298173 TI - Tako-tsubo cardiomyopathy precipitated by alcohol withdrawal. AB - A 57 year-old woman with no history of cardiac disease presented to the emergency department with confusion and seizures secondary to alcohol withdrawal. Elevated troponin levels and an electrocardiogram demonstrating global T-wave inversions prompted coronary angiography, which revealed coronary vessels free of significant disease. An echocardiogram showed both hypokinesis of the left ventricular mid-segments with apical involvement and a hyperkinetic base consistent with tako-tsubo cardiomyopathy (TCM). Several clinical conditions have been reported as triggers of TCM. We report a case of TCM in a post-menopausal woman that was precipitated by alcohol withdrawal. PMID- 22298174 TI - Myocardial infarction secondary to unintentional ingestion of hydrogen peroxide. AB - Ingestion of acid-containing household products, either accidentally or as a suicide attempt, is a common form of intoxication. A clear and odorless liquid, hydrogen peroxide is an oxidizing agent found in most households and many industrial environments. Cardiovascular manifestations of hydrogen peroxide ingestion are extremely rare. Here we report a 60 year-old woman with acute inferolateral myocardial infarction (MI) after hydrogen peroxide ingestion, who had no history of coronary artery disease. Physicians dealing with hydrogen peroxide ingestion in the emergency department should be aware of the probability of MI and obtain an electrocardiogram, even if the patient has no cardiac complaint. PMID- 22298175 TI - Anterior mitral leaflet perforation identified by real time three-dimensional transesophageal echocardiography. AB - With its unique en face view, real time three-dimensional transesophageal echocardiography has been reported to be more precise than conventional two dimensional studies in evaluating mitral regurgitation etiology, and can locate diseased segments correctly. We present a case with severe mitral regurgitation due to anterior mitral leaflet perforation. Intraoperative real time three dimensional transesophageal echocardiography demonstrated its value in diagnosis and surgical planning for this perforation, which had not been identified preoperatively. This technique should be applied more widely for dedicated mitral valve assessment in clinical practice. PMID- 22298176 TI - Coronary vasospasm during a regadenoson stress test. PMID- 22298177 TI - Dynamic variations of P-wave duration in a patient with acute decompensated congestive heart failure. AB - Interatrial block is an abnormally delayed atrial activation, characterized at ECG by prolonged P-wave duration (more than 110 ms), irrespective of morphology. We report the case of a patient with acute decompensated severe congestive heart failure, that at hospital admission showed a prolonged P-wave, which reverted after diuretic therapy. The dynamic change of the atrial P-wave correlates with clinical evolution and serum level modification of B-type natriuretic peptide. PMID- 22298178 TI - Recent innovations in the development of magnetic resonance imaging conditional pacemakers and implantable cardioverter-defibrillators. AB - The first generation of magnetic resonance conditional pacemakers and implantable cardioverter-defibrillators has finally arrived in clinical practice after many years of development. These devices have been optimized to properly function within magnetic fields of 1.5 T and ensure safe operation in controlled environments. Further progress is needed to develop a new generation of magnetic resonance imaging (MRI) conditional devices that can operate in higher powered MRI machines (3 T) which produce clearer images. PMID- 22298179 TI - Mitral valve myxoma: clinical features, current diagnostic approaches, and surgical management. AB - BACKGROUND: The purpose of this article is to document the clinical features of the unusual mitral valve myxoma based on the literature of recent years. METHODS: A literature retrieval of the mitral valve myxoma reported in recent years was made using the MEDLINE and EMBASE databases. The clinical information about this unusual disorder was collected and analyzed. RESULTS: Mitral valve myxoma showed female predilection. Their major symptoms were cardiovascular or cerebrovascular, in addition to constitutional or embolic. The diagnosis was usually made based on two- and three-dimensional transthoracic and/or transesophageal echocardiography, as well as magnetic resonance imaging in the current era. Surgical resection with mitral valve defect repair was the commonest remedy for mitral valve myxoma when mitral valve function could be preserved, and the mitral valve should be replaced when necessary. Patients showed good response to surgical treatment during the follow-up of 17.0 +/- 28.4 months after the operation. CONCLUSIONS: Two- and three-dimensional echocardiography and magnetic resonance imaging are the major diagnostic tools for the diagnosis of a cardiac myxoma. After diagnosis, surgery should be performed urgently, in order to prevent complications such as embolic events or obstruction of the mitral orifice. Due to the fact that myxomas can recur, regular, postoperative cardiological control is mandatory. PMID- 22298180 TI - Professor Zbigniew Religa (1938-2009). An outstanding cardiac surgeon. Director, Chancellor, member of Parliament, Senator, and Minister. PMID- 22298182 TI - Reversal of profound and "deep" residual rocuronium-induced neuromuscular blockade by sugammadex: a neurophysiological study. AB - BACKGROUND: Sugammadex is the first of a new class of selective relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade (NMB) induced by the aminosteroid neuromuscular blocking drugs rocuronium and vecuronium. Neuromuscular blocking drugs block the transmission from the peripheral nerve to the muscle units, with reduction and disappearance of the evoked electromyographic activity. Usually, neuromuscular monitoring for the investigational reversal drug is performed by calibrated acceleromyography. The efficacy of sugammadex in reversing profound and "deep" residual rocuronium induced NMB using myogenic motor evoked potentials (mMEPs) monitoring was evaluated. METHODS: In this prospective trial, 30 consenting patients undergoing propofol-remifentanil anesthesia for spine surgery were enrolled and divided into two groups: Group 1, reversal of profound NMB (sugammadex 16 mg/Kg, 3 minutes after rocuronium 1.2 mg/Kg) and Group 2, reversal of "deep" residual NMB (sugammadex 4 mg/Kg, 15 minutes after rocuronium 0.6 mg/Kg). Myogenic MEPs registrations of upper and lower limbs and the diaphragm were performed, as well as TOF monitoring. RESULTS: After injection of 4 mg/Kg of sugammadex, the means of recovery time of the basal mMEPs amplitudes (diaphragm, and lower limbs and upper limbs) were 124+/-9.6, 143+/-163, 151+/-207 sec, respectively whereas after 16 mg/Kg of sugammadex the times were 109+/-13.8, 124+/-0.6, and 135+/-14.1 sec. Times to TOF ratio 0.9 were 114+/-75 and 186+/-105 sec in Group 1 and 2, respectively. No serious adverse effects related to sugammadex and to electrical stimulation were reported. No reoccurrence of neuromuscular block was observed. CONCLUSION: Neurophysiological monitoring using mMEPs confirmed that sugammadex provided a complete recovery from profound and "deep" residual rocuronium-induced neuromuscular blockade. PMID- 22298185 TI - Coagulation monitoring under bleeding conditions: time to reconsider basic principles for our clinical decisions! PMID- 22298186 TI - Increased serum soluble CD147 levels in patients with systemic sclerosis: association with scleroderma renal crisis. AB - CD147 is a glycosylated membrane protein that belongs to the immunoglobulin superfamily. This study aimed to determine serum soluble CD147 (sCD147) levels and their clinical associations in patients with systemic sclerosis (SSc). Serum sCD147 levels were examined by enzyme-linked immunosorbent assay in 61 SSc patients and 24 healthy individuals. Serum sCD147 levels were significantly elevated in SSc patients compared with healthy individuals (P<0.001). Among patients with SSc, there were no differences in serum sCD147 levels between limited cutaneous (n030) and diffuse cutaneous SSc (n031). Patients with SSc who had elevated sCD147 levels had renal crisis more often than those with normal sCD147 levels (13% vs 0%; P<0.05). Serum sCD147 levels were increased in patients with SSc and associated with the presence of renal crisis. These results suggest that sCD147 may have a role in the development of renal crisis in SSc. Measurement of serum sCD147 may be useful for risk stratification for renal crisis in SSc. PMID- 22298187 TI - Unusual reinforcement of silicone rubber compounds containing mesoporous silica particles as inorganic fillers. AB - We fabricate mesoporous silica/silicone composites in a simple way and systematically examine their thermal stability, swelling characteristic, mechanical strength, and transparency. Simple calculations show that more than 90 vol% of mesopores are filled with silicone rubbers. Compared to non-porous silica/silicone composites, mesoporous silica/silicone composites showed a lower coefficient of linear thermal expansion (CTE). In addition, dramatic improvements of the tensile strength and Young's modulus are obtained with mesoporous silica/silicone composites. Furthermore, mesoporous silica/silicone composites show higher transparency than non-porous silica/silicone composites. PMID- 22298188 TI - Re: The efficacy and safety of ureteroscopy for ureteral calculi in pregnancy: our experience in 32 patients. PMID- 22298189 TI - Effect of Costus igneus stem extract on calcium oxalate urolithiasis in albino rats. AB - The effects of aqueous and ethanolic extracts of Costus igneus (stem) and isolated compounds lupeol and stigmasterol on calcium oxalate urolithiasis have been studied in male albino Wistar rats. Ethylene glycol feeding resulted in hyperoxaluria as well as increased renal excretion of calcium and oxalate. The increased deposition of stone-forming constituents in the urine, serum, and kidney homogenate of urolithic rats was significantly (p < 0.05) lowered by treatment using aqueous and ethanolic extracts of C. igneus (stem), and isolated compounds lupeol and stigmasterol. The calcium oxalate crystal deposition in the kidney was significantly greater in ethylene glycol-induced urolithic rats. After administration of aqueous and ethanolic extract of C. igneus, the deposition of calcium and oxalate was significantly lowered. Treatment with lupeol and stigmasterol significantly reduced the deposition of calcium and oxalate in the kidney, and also in the blood serum; the lipid profile serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels at 50 and 100 mg/kg were significantly (p < 0.05) lowered in urolithiatic rats. From this study, we conclude that both the treatments with aqueous and ethanolic extract of C. igneus (stem) and isolated compounds lupeol and stigmasterol had an inhibitory effect on calcium oxalate urinary stone. Lupeol and stigmasterol were identified from the stem of C. igneus by high-performance thin layer chromatography technique. The isolated compounds were confirmed by Fourier transform infrared (FTIR) and (13)C NMR spectra. PMID- 22298190 TI - Structural and electronic property responses to the arsenic/phosphorus exchange in GC-related DNA of the B-form. AB - The suggestion that phosphorus/arsenic replacement in DNA can play a role in living things has generated great controversy (Wolfe-Simon et al., Science 2011, 332, 1163). Examined here theoretically are substitution effects on Watson-Crick base pairing and base stacking patterns in realistic DNA subunits. Using duplex DNA models deoxyguanylyl-3',5'-deoxycytidine ([dGpdC](2) ) and deoxycytidyly 3',5'-deoxyguanosine ([dCpdG)](2) ), this research reveals that the geometric variations caused by the As/P exchange are small and are limited to the phosphate/arsenate groups. As/P replacement leads to alterations of ~0.15 A in P/As?O bond lengths and less than 1.5 degrees variations in O?P/As?O angles. The Watson-Crick base pairing and base stacking patterns are independent of the As/P replacement. The vertical electron detachment energies are also largely unaffected. However, the electron capture ability of the DNA units is improved by the As substitution. The arsenate is found to be the main electron acceptor in As DNA. The results are relevant to the possible existence of viable As-DNAs, at least in the guanine and cytosine (GC)-related B-form DNA. PMID- 22298191 TI - Leaky effect. PMID- 22298192 TI - Shattered details. PMID- 22298193 TI - Synthesis and optical properties of mesoporous beta-Co(OH)(2) /brilliant blue G (G250) hybrid hierarchical structures. AB - New mesoporous beta-Co(OH)(2) /brilliant blue G (G250) hybrid hierarchical structures constructed by thin mesocrystal nanosheets can be synthesized by a one step refluxing process under the synergistic effect of CTAB and G250. This approach opens up an avenue to access new novel inorganic/dye hybrid materials with hierarchical structures for pigment and electrocatalytic application. PMID- 22298194 TI - Pharmaceutical care for patients with breast and ovarian cancer. AB - PURPOSE: Individualized patient care may help reduce the incidence of adverse drug events in systemic cancer therapy. This study was conducted to explore the feasibility and potential of additional pharmaceutical care for breast and ovarian cancer patients. METHODS: The study was designed as a prospective, multicentered cohort study with a control group. Ninety-eight breast or ovarian cancer patients were recruited from outpatient oncology clinics and primary care oncologists: initially into the control group receiving standard care and after implementation of pharmaceutical care into the intervention group consisting of additional patient counseling on the management of treatment-associated adverse events and optimization of supportive medication. Primary outcome was the complete response to the antiemetic prophylaxis. Secondary endpoints were the severity of nausea, frequency of emesis, health-related quality of life, and patient satisfaction with information on cancer treatment education. RESULTS: Forty-eight patients were included in the control group and 50 in the intervention group. Of the patients, 35.4% in the control group and 76.0% in the intervention group (p < 0.001) had a complete response to the antiemetic prophylaxis. The severity of acute and delayed nausea was not reduced. The global health scale and two symptom scales (nausea and vomiting, appetite loss) of the EORTC QLQ-C30 questionnaire were positively affected by pharmaceutical care. Patient satisfaction with information was significantly higher in the intervention group. CONCLUSIONS: Patients with breast and ovarian cancer seem to benefit from pharmaceutical care, as suggested by improved patient-reported outcomes such as emetic episodes, quality of life, and patient satisfaction after implementation. PMID- 22298195 TI - Neural systems for speech and song in autism. AB - Despite language disabilities in autism, music abilities are frequently preserved. Paradoxically, brain regions associated with these functions typically overlap, enabling investigation of neural organization supporting speech and song in autism. Neural systems sensitive to speech and song were compared in low functioning autistic and age-matched control children using passive auditory stimulation during functional magnetic resonance and diffusion tensor imaging. Activation in left inferior frontal gyrus was reduced in autistic children relative to controls during speech stimulation, but was greater than controls during song stimulation. Functional connectivity for song relative to speech was also increased between left inferior frontal gyrus and superior temporal gyrus in autism, and large-scale connectivity showed increased frontal-posterior connections. Although fractional anisotropy of the left arcuate fasciculus was decreased in autistic children relative to controls, structural terminations of the arcuate fasciculus in inferior frontal gyrus were indistinguishable between autistic and control groups. Fractional anisotropy correlated with activity in left inferior frontal gyrus for both speech and song conditions. Together, these findings indicate that in autism, functional systems that process speech and song were more effectively engaged for song than for speech and projections of structural pathways associated with these functions were not distinguishable from controls. PMID- 22298196 TI - Nursing workforce issues: strategically positioning nurses to facilitate cancer prevention and control. AB - The number of cancer survivors is increasing, but at a staggering cost. These costs can be reduced or contained by preventing cancer and its recurrence. Nurses play a critical role in cancer prevention, a role that will rapidly expand as the number of oncology specialists decreases. It is crucial, therefore, that nurses increase their involvement in cancer prevention. To prepare nurses for this larger role, educational programs in cancer prevention and detection must be instituted for all nurses, particularly those in rural and medically underserved areas. The Professional Education for Prevention and Early Detection program at The University of Texas MD Anderson Cancer Center has developed two nurse education programs: outreach programs for nurses involved in the community and in house programs for those in clinical practice. These approaches have proven to be enormously effective in developing the nursing workforce as agents of cancer prevention. PMID- 22298197 TI - An update about tobacco and cancer: what clinicians should know. PMID- 22298198 TI - The Alaska Education and Research Towards Health (EARTH) Study: cancer risk factors. AB - The Alaska Education and Research Towards Health (EARTH) Study assessed cancer risk among 3,821 Alaska Native people (AN). We present the prevalence of selected cancer risk factors and comparison with Healthy People 2010 goals. Participants completed extensive computer-assisted self-administered questionnaires on diet, physical activity, tobacco and alcohol use, cancer screening, family history of cancer, and environmental exposures. Measurement data were collected on blood pressure, height, weight, waist/hip circumference, fasting serum lipids, and glucose. Cancer risk factors are high for the Alaska EARTH study population. For all risk factors studied except for vegetable consumption, Alaska EARTH Study participants did not meet Healthy People 2010 goals. This study is unique in providing questionnaire and measurement data of cancer risk factors on a larger study sample than any previous study among AN living in Alaska. Data show that the prevalence of most cancer risk factors exceeded national recommendations. Given the disease disparities that exist for the AN population, these data provide important baseline data that can be used to target health interventions and reduce health disparities. PMID- 22298199 TI - On ultrasound-induced microbubble oscillation in a capillary blood vessel and its implications for the blood-brain barrier. AB - The complex interaction between an ultrasound-driven microbubble and an enclosing capillary microvessel is investigated by means of a coupled, multidomain numerical model using the finite volume formulation. This system is of interest in the study of transient blood-brain barrier disruption (BBBD) for drug delivery applications. The compliant vessel structure is incorporated explicitly as a distinct domain described by a dedicated physical model. Red blood cells (RBCs) are taken into account as elastic solids in the blood plasma. We report the temporal and spatial development of transmural pressure (P(tm)) and wall shear stress (WSS) at the luminal endothelial interface, both of which are candidates for the yet unknown mediator of BBBD. The explicit introduction of RBCs shapes the P(tm) and WSS distributions and their derivatives markedly. While the peak values of these mechanical wall parameters are not affected considerably by the presence of RBCs, a pronounced increase in their spatial gradients is observed compared to a configuration with blood plasma alone. The novelty of our work lies in the explicit treatment of the vessel wall, and in the modelling of blood as a composite fluid, which we show to be relevant for the mechanical processes at the endothelium. PMID- 22298200 TI - Health-related quality of life among children with mental disorders: a systematic review. AB - PURPOSE: To systematically review studies about the quality of life (QOL) of children with various mental disorders relative to healthy controls and to describe limitations in these studies. METHODS: Relevant articles were searched using different databases, by checking reference lists and contacting experts. We included articles that either compared children with mental disorders to healthy controls/norm values or made such a comparison possible. RESULTS: Sixteen out of 4,560 articles met the pre-defined inclusion criteria. These studies revealed that the QOL of children with various mental disorders is compromised across multiple domains. The largest effect sizes were found for psychosocial and family related domains and for the total QOL score, whereas physical domains generally were less affected. The most important limitations in the existing literature include the lack of study samples drawn from the general population, the failure to use self-ratings, not considering item overlap between measuring QOL and assessing for the presence of a particular mental disorder, and not determining whether the children were receiving medication for their mental disorder. CONCLUSIONS: Children with mental disorders experience a considerable reduction in QOL across various domains. Research studies that avoid previous limitations are crucial to fill existing knowledge gaps. PMID- 22298201 TI - Development of the Healthy Pathways Parent-Report Scales. AB - PURPOSE: To describe the development of the Healthy Pathways Parent-Report Scales, measures of health, illness, well-being, and achievement among youth in middle childhood and adolescence. METHODS: The Healthy Pathways Scales were derived from the Child Health and Illness Profile (CHIP) instruments. The CHIP domains of Comfort, Risk Avoidance, Satisfaction, and Resilience were modified to reflect advances in child health conceptualization. Classical test and modern psychometric analyses were conducted using data collected from 1,527 parents of children aged 9-14 years. Intra-class correlation and differential item functioning analyses were used to evaluate the extent of child-parent agreement on the Healthy Pathways Scales. RESULTS: After minor revisions, 11 of the 12 scales were found to measure unidimensional parent-assessed outcomes comprehensively (full range of the latent trait) and efficiently (a minimal number of items). Scales were unbiased by age, gender, and geographic location. The construct validity of the scales was supported by their capacity to differentiate children with and without chronic illnesses and to detect expected age and gender differences. Child-parent agreement was poor to moderate at both the scale and item levels. CONCLUSIONS: The Healthy Pathways Parent-Report Scales may be used to reliably, accurately, and efficiently assess unidimensional aspects of health, illness, well-being, and achievement in clinical and population-based research studies involving youth in middle childhood and adolescence. PMID- 22298202 TI - Worsening trends and increasing disparities in health-related quality of life: evidence from two French population-based cross-sectional surveys, 1995-2003. AB - PURPOSE: To investigate time trends in health-related quality of life (HRQoL) in France and to report existing and changing demographic, socioeconomic, and geographic disparities. METHODS: Data were drawn from two independent national cross-sectional surveys conducted in 1995 and 2003, including 3,243 individuals aged 18-84 in 1995 and 22,743 in 2003. HRQoL was measured with the 8 subscales of the French version of the SF-36. RESULTS: After multiple linear regression, a significant decrease was observed between 1995 and 2003 in all scales scores, from -0.11 adjusted standard deviations for Social Functioning (95% CI: -0.15 to 0.08) to -0.23 for Vitality (-0.26 to -0.19). Increasing age, female gender, divorce/widowhood, lowest educational levels, chronic conditions, and living in the Northern region were identified as independent predictors of lower HRQoL scores. Testing interactions showed significantly greater differences between 1995 and 2003 for subjects aged 75-84 and for least educated subjects (Physical Functioning, General Health). The Gini index increased for all scales. CONCLUSIONS: We report evidence of worsening trends and possibly increasing demographic, socioeconomic, and regional disparities in HRQoL between 1995 and 2003 in France. Monitoring HRQoL in populations can provide unique and sensitive data, complementary to classical indicators based on mortality and morbidity. PMID- 22298203 TI - Control-matched computational evaluation of tendo-femoral contact in patients with posterior-stabilized total knee arthroplasty. AB - Painful patellar crepitus is a potential complication in up to 14% of patients following posterior-stabilized (PS) total knee arthroplasty (TKA). A recent clinical study identified influential patient and surgical variables by comparing a group of crepitus patients with controls matched for age, sex, and body mass index. The purpose of our study was to evaluate effects of variables identified as significant in the clinical study, including patellar ligament length, femoral component flexion, patellar button size, and position of the joint line, on contact between the quadriceps tendon and the PS femoral component. A previously verified finite element model was utilized to estimate tendo-femoral contact during deep flexion activity. Using discrete perturbations, the computational model confirmed the clinical findings in that an increased patellar ligament length, flexed femoral component, lowered joint line, and larger patellar component all reduced potentially deleterious contact near the intercondylar notch. With the selected level of anatomic and component alignment perturbations, the most influential factor affecting tendo-femoral contact was patellar ligament length. Three crepitus patients with matched controls were subsequently modeled, and contact with the anterior border of the notch was present in each crepitus patient, but none of the controls. Alternative surgical alignments for these patients were evaluated to improve the potential long-term outcomes. By characterizing conditions that may lead to painful crepitus, the modeling approach supports clinicians by identifying pre-surgical indicators and important alignment parameters to control intraoperatively. PMID- 22298204 TI - Maternal outcome monitoring: induction of labor versus spontaneous onset of labor a retrospective data analysis. AB - PURPOSE: To determine the efficacy and maternal complication rates of induction of labor, and to identify a concrete point in time for induction with the lowest possible risk for adverse events. METHODS: We designed a retrospective data analysis of all births at the general hospital of Vienna from 2003 to 2008(n = 16,872) and compared maternal complications of induced labors from 38 or more weeks of gestation versus spontaneous deliveries. The ethical committee of the General Hospital of Vienna and the Medical University of Vienna monitored this study and provided approval. RESULTS: Women who had induction between 38 and 42 weeks of gestation (n = 1,254) had a significant higher risk for the need of a secondary cesarean (15.2 vs. 8.6%;p?0.001) and a higher chance for abnormally adherent placentas (1.5 vs. 2.5%; p = 0.13). The amount of maternal blood loss was equal in both groups. Concerning the question when to induct labor, there was no significant difference of distribution of complications between induced labors at term and induction within the next 10 days. CONCLUSIONS: This study suggests that induction is associated with a higher risk for secondary cesareans and abnormally adherent placentas. The exact time of induction seems to be irrelevant between expected date of delivery and the next 10 days. PMID- 22298205 TI - Pseudocholinesterase in gestational diabetes: positive correlation with LDL and negative correlation with triglyceride. AB - OBJECTIVE: Low pseudocholinesterase (PChE) activity accompanies pregnancy, liver disease, renal failure, and certain drug therapies. The aim of this study was to investigate a possible relationship among PChE and plasma insulin levels, lipid profile, and inflammatory response ingestational diabetes. METHODS: This study included 165 women aged 20-40 years. Subjects were divided into four groups as follows:Control group, 29 non-pregnant healthy women; GroupNGT, 61 healthy pregnant women (normal glucose tolerance);Group GD, 62 pregnant women with gestational diabetes; and Group AGT, 13 pregnant women with abnormal glucose tolerance. Gestational ages were between 34 and 40 weeks. Plasma PChE, triglyceride, high-/lowdensity lipoprotein (HDL, LDL), glycated hemoglobin A1c(HbA1c), insulin, C-reactive protein (CRP), and white blood cell (WBC) levels were measured in all subjects. RESULTS: There were no statistically significant differences in plasma PChE, insulin, and LDL levels between the groups. Plasma triglyceride, HbA1c, WBC, and CRP levels were significantly higher in Group GD and Group AGT compared to the other groups (P?0.000). There was a positive correlation between increased PChE and LDL,while a negative correlation was observed between PChE and triglyceride in Group GD. There was a positive correlation between increased CRP and HbA1c and a negative correlation among CRP and LDL and triglyceride in Group GD. CONCLUSION: PChE activity was not significantly different between the groups. However, there was a positive correlation between PChE and LDL levels in pregnant women with GD, suggesting that LDL levels in pregnant women with GD may help to predict the risk of prolonged apnea in situations in which PChE activity cannot be measured. PMID- 22298206 TI - Chronic kidney disease of unknown aetiology in the North Central Province of Sri Lanka: trying to unravel the mystery. PMID- 22298207 TI - Validation of the Sinhala version of the Montreal Cognitive Assessment in screening for dementia. AB - OBJECTIVES: To validate the Sinhala version of the Montreal Cognitive Assessment (MoCA) scale in screening for dementia. METHODS: The MoCA translation and cultural adaptation was carried using a combined qualitative and quantitative approach. Sample size was calculated to detect a targeted sensitivity of 85% and a specificity of 85%. Sample consisted of 49 participants diagnosed with dementia of the Alzheimer's type (AD) according to DSM-IV criteria and 49 normal controls (NC) aged >=50 years. All subjects were administered the Mini Mental State Examination (MMSE) and MoCA Sinhala version (MoCA-S). Concurrent validity was assessed using Pearson correlation coefficients between the MoCA-S scores and MMSE scores. Criterion validity was assessed using receiver operating characteristic (ROC) analysis. RESULTS: Mean MoCA scores between NC (26.71, SD 2.4) and AD group (16.78, SD 5.9) were significantly different (t=10.8, p<0.001). Cronbach's alpha of 0.818 indicated good internal consistency. Attention (digit span, sustained attention, and the serial 7 calculation task) had the highest discriminant ability followed by visuospatial skills (trail making, cube drawing and clock drawing). Naming had poor discriminant ability. There was a high, positive correlation between MoCA-S total scores and MMSE total scores. (r=0.907, p<0.001). The area under the ROC curve was 0.975 (95%CI 0.94-1.0) for the MoCA and 0.928 (95% CI 0.87-0.98) for MMSE. A cut-off value of 24 provided the best balance between sensitivity (98.0 7%) and specificity (79.6 %). CONCLUSION: MoCA S is a valid and reliable instrument which can be used as a brief screening instrument for dementia in Sri Lanka. PMID- 22298208 TI - Mental health status and risk factors for mental health problems in left-behind children of women migrant workers in Sri Lanka. AB - INTRODUCTION: Many married Sri Lankan women annually migrate for employment overseas. Despite widely speculated psychological consequences in these children, their mental health status has not been systematically studied using validated instruments. OBJECTIVES: To describe mental health status of children of women overseas workers and compare that with children of locally employed women, and to describe socio-demographic factors and risk factors associated with abnormal mental health in these children. METHODS: A cross sectional comparative survey was conducted among 253 children (aged 5-10 years) of women migrant workers in the Colombo District and age and sex matched controls from same neighbourhood. Tools used were the validated Sinhala translation of Child Behaviour Check List (CBCL-S) and questionnaires on socio-demographic/risk factors and school functioning. RESULTS: Mean CBCL-S scores and proportion of children with mental health problems were significantly higher in the study group. Not having an elder sibling, father not living with child, mother educated up to grade 5 or less, change of principal carer (PC) twice or more, living with a relative (or not living in own home), child not communicating freely with PC, and not being permitted to engage in recreational activities at school were significantly associated with abnormal mental health of children of migrant women. CONCLUSIONS: A high awareness is required among health and social care authorities regarding mental health problems in these children and relevant risk factors in order to take preventive measures. PMID- 22298209 TI - Local recurrence of rectal cancer in patients not receiving neoadjuvant therapy - the importance of resection margins. AB - OBJECTIVES: Local recurrence of rectal cancer reduces quality of life and survival. A multi-factorial linear logistic model was used to analyse risk factors for local recurrence in rectal cancer in patients not receiving preoperative chemo-radiation. METHODS: A case-control study of patients with rectal cancer having surgery with curative intent, between 1996 and 2008. Eighteen putative risk factors for local recurrence were subjected to uni-variate analysis. Significant factors were selected for multi-factorial analysis. RESULTS: Twenty-one patients with local recurrence (cases) and 78 controls were selected. Uni-variate analysis showed significant associations with recurrence for nodal stage (N) (p=0.027), metastasis (M) (p=0.009), adjuvant chemotherapy (p=0.039), positive resection margin (R) (p=0.018) and American Joint Committee for Cancer (AJCC) tumours above stage II (p=0.043). Significant uni-variate odds ratios (OR) were obtained for the same factors. Two linear logistic models were fitted as (1) N, M, R1 status and adjuvant chemotherapy and (2) AJCC stage, R1 status and adjuvant chemotherapy. From both models, the only factor significantly associated (p <= 0.01) with local recurrence was found to be a positive resection margin (OR 4.81 and 5.51 respectively). CONCLUSIONS: A positive resection margin is the single factor affecting local recurrence of rectal cancer in patients not receiving neo-adjuvant therapy. PMID- 22298210 TI - Oesophageal injury suspected to be due to doxycycline ingestion. PMID- 22298211 TI - Funnel plots for comparing institutional performance of antenatal care in pregnant women with diabetes. PMID- 22298212 TI - A case of olfactory reference syndrome. PMID- 22298213 TI - Congenital adrenal hyperplasia and hypokalaemic paralysis. PMID- 22298214 TI - Nutraceuticals: concepts and controversies. PMID- 22298215 TI - Outcome of delayed allopathic management of orthopaedic injuries initially treated by traditional bone healers. PMID- 22298216 TI - Shift in the transmission pattern of dengue serotypes and concurrent infection with more than one dengue virus serotype. PMID- 22298217 TI - First successful in vitro culture of Leishmania sp. causing autochthonous visceral leishmaniasis in Sri Lanka. PMID- 22298218 TI - Scalp metastasis in a patient with phaeochromocytoma. PMID- 22298219 TI - A study on suicide by self immolation. PMID- 22298220 TI - Post partum depression - a problem that needs urgent attention. PMID- 22298221 TI - Measles, mumps, rubella (MMR) vaccine - a reply (1). PMID- 22298222 TI - Measles, mumps, rubella (MMR) vaccine - a reply (2). PMID- 22298223 TI - Focal therapy of prostate cancer: evidence-based analysis for modern selection criteria. AB - Focal therapy for prostate cancer has been increasingly utilized with the goal of effective disease control while maximizing patient functional outcomes. The optimal patient selection criteria are not known and therefore are not standardized. This review compares the available expert panel consensus guidelines with the selection criteria utilized in recently published focal therapy trials. Because the data from focal trials are still maturing, the currently enrolling clinical trials are reviewed as well. In addition, the recent literature regarding technological advances in prostate biopsy and imaging strategies are added to the current guidelines to recommend a rationale for patient selection. PMID- 22298225 TI - Achievement of a uniform high standard of knowledge in Intensive Care throughout Europe: a major step ahead. PMID- 22298224 TI - Enhanced discrimination of DNA molecules in nanofluidic channels through multiple measurements. AB - Nanofluidic sensing elements have been the focus of recent experiments for numerous applications ranging from nucleic acid fragment sizing to single molecule DNA sequencing. These applications critically rely on high measurement fidelity, and methods to increase resolution are required. Herein, we describe fabrication and testing of a nanochannel device that enhances measurement resolution by performing multiple measurements (>100) on single DNA molecules. The enhanced measurement resolution enabled length discrimination between a mixture of lambda-DNA (48.5 kbp) and T7 DNA (39.9 kbp) molecules, which were detected as transient current changes during translocation of the molecules through the nanochannel. As long DNA molecules are difficult to resolve quickly and with high fidelity with conventional electrophoresis, this approach may yield potentially portable, direct electrical sizing of DNA fragments with high sensitivity and resolution. PMID- 22298227 TI - Primary cardiac leiomyoma of the ventricular septum: a rare form of pediatric intracardiac tumor. AB - A case of ventricular septal tumor diagnosed in 7-month-old boy is reported. An echocardiogram was performed for investigation of a heart murmur in an otherwise healthy infant. He remained asymptomatic, and the tumor had a very slow growth. When the boy was 9 years old, partial surgical excision was performed for right ventricular outflow tract obstruction. Histology showed a primary cardiac leiomyoma. To the authors' knowledge, a primary cardiac leiomyoma of the ventricular septum has not been reported previously. PMID- 22298226 TI - The 'Effects of Transfusion Thresholds on Neurocognitive Outcome of Extremely Low Birth-Weight Infants (ETTNO)' Study: Background, Aims, and Study Protocol. AB - Background: Infants with extremely low birth weight uniformly develop anemia of prematurity and frequently require red blood cell transfusions (RBCTs). Although RBCT is widely practiced, the indications remain controversial in the absence of conclusive data on the long-term effects of RBCT. Objectives: To summarize the current equipoise and to outline the study protocol of the 'Effects of Transfusion Thresholds on Neurocognitive Outcome of extremely low birth-weight infants (ETTNO)' study. Methods: Review of the literature and design of a large pragmatic randomized controlled trial of restrictive versus liberal RBCT guidelines enrolling 920 infants with birth weights of 400-999 g with long-term neurodevelopmental follow-up. Results and Conclusions: The results of ETTNO will provide definite data about the efficacy and safety of restrictive versus liberal RBCT guidelines in very preterm infants. PMID- 22298228 TI - Attention-deficit/hyperactivity disorder, stimulant therapy, and the patient with congenital heart disease: evidence and reason. AB - Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood, and congenital heart disease (CHD) is the most common form of birth defect. Children with CHD are at increased risk for neurodevelopmental disorders such as ADHD. Stimulant medications, specifically methylphenidates and amphetamines, are frequently prescribed and effective in reducing the symptoms of ADHD. Despite their efficacy and long history of use, the safety of these medications has recently come into question due to isolated reports describing sudden unexplained death of children undergoing treatment. This review summarizes the current literature on the cardiovascular risks associated with the use of pharmacologic therapy for ADHD, with an emphasis on patients who had CHD. PMID- 22298230 TI - Highly flexible pseudocapacitor based on freestanding heterogeneous MnO2/conductive polymer nanowire arrays. AB - Flexible electronics such as wearable electronic clothing, paper-like electronic devices, and flexible biomedical diagnostic devices are expected to be commercialized in the near future. Flexible energy storage will be needed to power these devices. Supercapacitor devices based on freestanding nanowire arrays are promising high power sources for these flexible electronics. Electrodes for these supercapacitor devices consisting of heterogeneous coaxial nanowires of poly (3,4-ethylenedioxythiophene) (PEDOT)-shell and MnO(2)-core materials have been shown in a half cell system to have improved capacitance and rate capabilities when compared to their pure nanomaterials; however, their performance in a full cell system has not been fully investigated. Herein, these coaxial nanowires are tested in both a symmetric and an asymmetric (utilizing a PEDOT nanowire anode) full cell configuration in the aspect of charge storage, charge rate, and flexibility without using any carbon additives and polymer binders. It is found that the asymmetric cell outperforms the symmetric cell in terms of energy density, rate capability, and cycle ability. The asymmetric device's electrode materials display an energy density of 9.8 Wh/kg even at a high power density of 850 W kg(-1). This device is highly flexible and shows fast charging and discharging while still maintaining 86% of its energy density even under a highly flexed state. The total device is shown to have a total capacitance of 0.26 F at a maximum voltage of 1.7 V, which is capable of providing enough energy to power small portable devices. PMID- 22298229 TI - Review of inhaled nitric oxide in the pediatric cardiac surgery setting. AB - Surgical intervention for congenital heart disease (CHD) can be complicated by pulmonary hypertension (PH), which increases morbidity, mortality, and medical burden. Consequently, postoperative management of PH is an important clinical consideration to improve outcomes. Inhaled nitric oxide (iNO) is a widely accepted standard of care for PH and has been studied in the context of cardiac surgery for CHD. However, large randomized, double-blind, placebo-controlled, multicenter clinical trials in pediatric patients are limited. This review will provide an overview of the clinical studies in this setting and will discuss general treatment considerations to facilitate a better understanding of the clinical use of iNO for PH after pediatric cardiac surgery. PMID- 22298231 TI - Increased lung cancer risk among bricklayers in an Italian population-based case control study. AB - BACKGROUND: Bricklayers may be at increased risk of lung cancer, although a firm association has not been established. We examined this association within the EAGLE (Environment And Genetics in Lung cancer Etiology) study, a population based case-control study conducted in Italy between 2002 and 2005. METHODS: For men in selected occupations in the construction sector we calculated smoking adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). For bricklayers we estimated the population attributable fraction (PAF) and the attributable community risk (ACR). RESULTS: We found increased lung cancer risk for bricklayers (OR 1.57, 95% CI 1.12-2.21; 147 cases, 81 controls). The PAF was 3.5% (95% CI 0.6-6.3), corresponding to an ACR of 3.6 cases annually per 100,000 men (95% CI 0.6-6.6) [corrected] in the whole community. Among bricklayers, there were increased risks for squamous cell (OR 2.03, 95% CI 1.32-3.13, 56 exposed cases) and small cell carcinomas (OR 2.29, 95% CI 1.29-4.07, 21 exposed cases), while no excess (OR 1.06, 95% CI 0.68-1.65, 41 exposed cases) was found for adenocarcinoma. CONCLUSIONS: Our findings provide additional evidence of increased lung cancer risk in Italian bricklayers. The association is plausible because they are exposed to several carcinogens, notably crystalline silica. PMID- 22298233 TI - Genomic instability: Shattered details. PMID- 22298232 TI - Isolation, structure determination, and synthesis of allo-RA-V and neo-RA-V, RA series bicyclic peptides from Rubia cordifolia L. AB - Two bicyclic hexapeptides, allo-RA-V (4) and neo-RA-V (5), and one cyclic hexapeptide, O-seco-RA-V (6), were isolated from the roots of Rubia cordifolia L. Their gross structures were elucidated on the basis of spectroscopic analysis and X-ray crystallography of compound 5. The absolute stereochemistry of compounds 4 and 5 were established by their total syntheses, and the absolute stereochemistry of compound 6 by chemical correlation with deoxybouvardin (3). Comparison of the 3D structures of highly active RA-VII (1) with less-active compounds 4 and 5 suggests that the orientation of the Tyr-5 and/or Tyr-6 phenyl rings plays a significant role in their biological activity. The isolation of peptides 4-6, along with compound 3, and the comparison of their structures seem to indicate that peptide 6 may be the common precursor to bicyclic peptides 3-5 in the plant. PMID- 22298234 TI - Fourier transform general formula for systematic potentials. AB - For calculating molecular integrals of systematic potentials, a three-dimensional (3D) Fourier transform general formula can be derived, by the use of the Abel summation method. The present general formula contains all 3D Fourier transform formulas which are well known as Bethe-Salpeter formulas (Bethe and Salpeter, Handbuch der Physik, Bd. XXXV, 1957) as special cases. It is shown that, in several of the Bethe-Salpeter formulas, the integral does not converge in the meaning of the Riemann integral but converges in the meaning of a hyper function as the Schwartz distribution. For showing an effectiveness of the present general formula, the convergence condition of molecular integrals is derived generally for all of the present potentials. It is found that molecular integrals can be converged in the meaning of the Riemann integral for the present potentials, except for those for extra super singular potentials. It is also found that the convergence condition of molecular integrals over the Slater-type orbitals is exactly the same as that of the corresponding integrals over the Gaussian-type orbitals for the present systematic potentials. For showing more effectiveness, the molecular integral over the gauge-including atomic orbitals is derived for the magnetic dipole-same-dipole interaction. PMID- 22298235 TI - The anatomic study of clival screw fixation for the craniovertebral region. AB - PURPOSE: To study the anatomic parameters related to clival screw and establish reference data concerning the craniovertebral fixation technique. METHODS: Morphometric measurement of the clivus and the surrounding anatomic structures were obtained on 41 dry bone specimens. Then, 2-D CT reconstruction of the craniovertebral region of 30 patients (19 men and 11 women, ranging in age from 20-64 years with an average age of 38.8 years) were performed to measure the safety range for a 3.5-mm screw placement. Nine entry points were evaluated. Finally, one male fresh cadaver specimen (age 46 years) was dissected to observe the craniovertebral region. RESULTS: The clivus faces the basilar artery, the V ~ XII cranial nerves, the pons, and ventral medulla oblongata at its intracranial surface. The longitudinal diameter of extracranial clivus was 25.87 +/- 2.64 mm. The narrowest diameter of the clivus was 12.84 +/- 1.08 mm, the distance between the left and right hypoglossal canal was 32.70 +/- 2.09 mm at its widest part. The distance between the left and right structures, the maximum value was 49.31 +/- 4.16 mm at carotid canal, the minimum value was 16.54 +/- 2.04 mm at the occipital condyle. The measurement of clival screws placement simulation via 2-D CT reconstruction images shows the maximum upper insertion angle of three components the optimal entry points, the candidate points, the limit entry points was 130.19 degrees , 125.23 degrees and 85.72 degrees , and the total mean screw length was 7.57, 10.13 and 15.6 mm at the vertical entry angle, respectively. CONCLUSIONS: Clival screw placement is a viable option for craniovertebral fixation. There is a safe scope for the screw length and angle of the screw placement. And, these parameters obtained in the present study will be helpful for anyone contemplating the use of clival screw fixation. PMID- 22298237 TI - Answer to the Letter to the Editor of G. Supp concerning manuscript "Centralization in patients with sciatica: are pain responses to repeated movement and positioning associated with outcome or types of disc lesions?" by Hanne B. Albert et al. Eur Spine J, 2011 Sept 23 [Epub ahead of print]. PMID- 22298236 TI - The normative score and the cut-off value of the Oswestry Disability Index (ODI). AB - PURPOSE: The Oswestry Disability Index (ODI) is one of the most common scoring systems used for patients with low back pain (LBP). Although the normative score of the ODI was reported to be 10.19 in a review article, no study has calculated the normative score after adjusting the value based on the age distribution. In addition, none of the previous studies has estimated the cut-off value which separates LBP with disability from LBP without disability. The purpose of this study was to estimate the normative score by adjusting the data for age distribution in Japan, and to determine the cut-off value which separates LBP with disability from LBP without disability. METHODS: We conducted an internet survey on LBP using the Japanese version of the ODQ. A total of 1,200 respondents, composed of 100 males and 100 females in each age group (from the 20s to 70s), participated in this study. We also asked them to provide information about their backgrounds. We estimated the normative score after correcting for the age distribution of Japan. We also estimated the ODI of those with or without disability, the factors associated with the ODI, and the cut-off value which separates LBP with disability from LBP without disability. RESULTS: The participants' backgrounds were similar to the national survey. The normative score of the ODI was estimated at 8.73. The ODI of the LBP with disability group was 22.07. Those with sciatica and obese subjects showed higher ODI than those without. The optimal cut-off value was estimated to be 12. CONCLUSIONS: We defined the normative score and the cut-off value of the ODI. PMID- 22298238 TI - Calculation of midplane dose for total body irradiation from entrance and exit dose MOSFET measurements. AB - This work is the development of a MOSFET based surface in vivo dosimetry system for total body irradiation patients treated with bilateral extended SSD beams using PMMA missing tissue compensators adjacent to the patient. An empirical formula to calculate midplane dose from MOSFET measured entrance and exit doses has been derived. The dependency of surface dose on the air-gap between the spoiler and the surface was investigated by suspending a spoiler above a water phantom, and taking percentage depth dose measurements (PDD). Exit and entrances doses were measured with MOSFETs in conjunction with midplane doses measured with an ion chamber. The entrance and exit doses were combined using an exponential attenuation formula to give an estimate of midplane dose and were compared to the midplane ion chamber measurement for a range of phantom thicknesses. Having a maximum PDD at the surface simplifies the prediction of midplane dose, which is achieved by ensuring that the air gap between the compensator and the surface is less than 10 cm. The comparison of estimated midplane dose and measured midplane dose showed no dependence on phantom thickness and an average correction factor of 0.88 was found. If the missing tissue compensators are kept within 10 cm of the patient then MOSFET measurements of entrance and exit dose can predict the midplane dose for the patient. PMID- 22298239 TI - Morbidity of foreign travelers in Attica, Greece: a retrospective study. AB - Over the last decade, travel medicine was mainly focused on the epidemiology of diseases among travelers to developing countries. However, less is known about travel-related morbidity in Europe. We evaluated the demographic and clinical characteristics of foreign travelers to Greece during a 5-year period (01/01/2005 - 31/12/2009) who sought medical services from a network of physicians performing house-call visits (SOS Doctors) in the area of Attica, Greece. Overall, 3,414 foreign travelers [children (<=18 years of age): 27%] were identified; 151 (4.4%) required transfer to a hospital. The most common clinical entities were: respiratory disorders (34%), diarrheal disease (19%), musculoskeletal (12%), dermatologic (7%), non-diarrheal gastrointestinal (6%), and genitourinary (5%) disorders. Respiratory disorders were the most frequent diagnosis during all seasons, followed by diarrheal gastrointestinal and musculoskeletal disorders. Respiratory and dental conditions were observed significantly more frequently in children. Respiratory disorders were observed significantly more frequently during winter (47%) compared to spring (36.7%), summer (30.9%), and autumn (30.5%), (p < 0.01). Despite the limitations of the retrospective methodology, our findings suggest that mild, self-limited respiratory events may be the prevalent cause for seeking primary health care during travel to Greece. Our findings may be extrapolated to other countries with similar climatic and socioeconomic status. PMID- 22298240 TI - Clinical and epidemiological characteristics of adult patients hospitalized for erysipelas and cellulitis. AB - The purpose of this investigation was to analyze the clinical and epidemiological aspects of all cases of erysipelas and infectious cellulitis admitted to a tertiary hospital during a period of five years. All patients admitted with the main diagnosis of erysipelas or cellulitis to the Department of Dermatology of the author's institution from January 2005 to May 2010 were included. Seventy patients were identified and their medical records were retrospectively reviewed so as to record the epidemiological and clinical data. Univariate and multivariable analyses were performed to analyze variables that predicted longer length of stay. The frequency of cellulitis in the lower limbs was higher in men and patients older than 65 years. Moderate/severe cellulitis in patients with basal comorbidity followed by a poor response to oral antibiotic therapy for 48 h were the most common reasons for admission. At arrival, four patients had abscessed areas. Fourteen patients developed local complications and 18 cases developed general in-hospital complications. Most patients improved or were healed with intravenous amoxicillin-clavulanate 1 g-200 mg/8 h. Intravenous amoxicillin-clavulanate 1 g-200 mg/8 h may be a good choice for empiric treatment in our setting. The development of in-hospital complications and the need for changing empiric antibiotic therapy were significant and independent variables associated with longer length of stay. PMID- 22298241 TI - Time to positivity of blood culture association with clinical presentation, prognosis and ESBL-production in Escherichia coli bacteremia. AB - The time to positivity (TTP) of blood cultures has been associated with increased mortality in bacteremia caused by several microorganisms. The aim of this study is to evaluate the relationship between TTP and prognosis, clinical presentation and extended spectrum B-lactamase (ESBL)-production in patients with Escherichia coli bacteremia. This is a retrospective observational study involving 226 adult patients with E. coli bacteremia. Data collected included underlying diseases, clinical presentation, prognosis factors, TTP, ESBL-production and outcome. Thirty-one (14%) patients had severe sepsis and 29 (13%) septic shock at presentation. Thirty-three (14%) strains were ESBL-producers. Thirty-nine (17%) patients died during admission and 17 (7.5%) within 48 hours. The median TTP was 8.3 hours (range, 0.42-76.5). It was significantly shorter in patients with septic shock (6.23 h, range 1.12-47.29 h vs. 8.51 h, range 0.42-76.50 h; p = 0.018). Rapid growth of E. coli, Pitt index >1.5, non-urinary source and Charlson score >2 were selected as independent risk factors of in-hospital mortality by the multivariate analysis. ESBL-production was not associated with modifications in TTP. Lower TTP is an independent risk factor for septic shock and poor outcome in episodes of E. coli bacteremia. The TTP in E. coli bacteremia is not significantly modified by ESBL-production. PMID- 22298242 TI - Lipooligosaccharide locus classes are associated with certain Campylobacter jejuni multilocus sequence types. AB - The lipooligosaccharide (LOS) locus class was determined using polymerase chain reaction (PCR) in 335 Finnish Campylobacter jejuni strains isolated from humans, poultry and bovines with known multilocus sequence types. The results revealed an association between clonal complexes/sequence types (STs) and LOS locus classes. Based on these results, we further predicted the LOS locus classes distribution among the STs of 209 additional C. jejuni strains from Finnish human domestically acquired infections. Non-sialylated LOS locus classes were associated with STs that comprised ~55% of patient strains. Sialylated LOS locus classes A and B were associated with STs infrequently isolated, whereas class C was correlated with the ST-21 complex, found in ~14% of human strains. A combination of the LOS locus class and multilocus sequence type may provide new information on the epidemiology and association of C. jejuni strains with certain disease outcomes. PMID- 22298243 TI - Outcomes and prognostic factors in patients with haematological malignancy admitted to a specialist cancer intensive care unit: a 5 yr study. AB - BACKGROUND: Long-held assumptions of poor prognoses for patients with haematological malignancies (HM) have meant that clinicians have been reluctant to admit them to the intensive care unit (ICU). We aimed to evaluate ICU, in hospital, and 6 month mortality and to identify predictors for in-hospital mortality. METHODS: A cohort study in a specialist cancer ICU of adult HM patients admitted over 5 yr. Data acquired included: patient characteristics, haematological diagnosis, haematopoietic stem cell transplant (HSCT), reason for ICU admission, and APACHE II scores. Laboratory values, organ failures, and level of organ support were recorded on ICU admission. Predictors for in-hospital mortality were evaluated using uni- and multivariate analysis. RESULTS: Of 199 patients, median age was 58 yr [inter-quartile range (IQR) 46-66], 51.7% were emergency admissions, 42.2% post-HSCT, 51.9% required mechanical ventilation, median APACHE II was 21 (IQR 16-25), and median organ failure numbered 2 (IQR 1 4). ICU, in-hospital, and 6 month mortalities were 33.7%, 45.7%, and 59.3%, respectively. Univariate analysis revealed bilirubin >32 umol litre(-1), mechanical ventilation, >=2 organ failures, renal replacement therapy, vasopressor support (all P<0.001), graft-vs-host disease (P=0.007), APACHE II score (P=0.02), platelets <=20*10(9) litre(-1) (P=0.03), and proven invasive fungal infection (P=0.04) were associated with in-hospital mortality. Multivariate analysis revealed that >=2 organ failures [odds ratio (OR) 5.62; 95% confidence interval (95% CI), 2.30-13.70] and mechanical ventilation (OR 3.03; 95% CI, 1.33-6.90) were independently associated with in-hospital mortality. CONCLUSIONS: Mortality was lower than in previous studies. Mechanical ventilation and >=2 organ failures were independently associated with in-hospital mortality. 'Traditional' variables such as neutropenia, transplantation status, and APACHE II score no longer appear to be predictive. PMID- 22298244 TI - ADAMTS13 and Von Willebrand factor in patients undergoing hemodialysis. AB - Hemodialysis (HD) is associated with increasing thrombotic trend. Vascular access thrombosis (VAT) increases morbidity in HD patients. The aim of this study was to evaluate ADAMTS13 and VWF plasma levels from patients undergoing HD as putative biomarkers of the hypercoagulability state, as well the association between these markers and VAT occurrence. This study included 195 patients on HD for more than 6 months. HD patients were allocated into two groups according to the occurrence or not of previous episode of VAT; HD with VAT (N = 46) and HD without VAT (N = 149). ADAMTS13 and VWF were performed by ELISA. There was no significant difference between HD patients with and without VAT for ADAMTS13 and VWF levels. However, VWF levels were higher (P < 0.001) and ADAMTS13 were lower (P < 0.001) in HD patients, comparing to the control group composed by healthy subjects without kidney disease, age and sex-matched (N = 80). Taken together our data suggest a potential role of the kidneys function compromised on ADAMTS13 synthesis or metabolism, regardless other known sources of ADAMTS13. The imbalance between ADAMTS13 and VWF levels does not explain the development of VAT in HD patients by itself, although it should contribute for the hypercoagulability state. Therefore, additional studies to identify other risk factors are warranted and essential for better management of HD patients. PMID- 22298246 TI - Digital microfluidic high-throughput printing of single metal-organic framework crystals. AB - The first microfluidic method for accurately depositing monodisperse single MOF crystals is presented, enabling unprecedented high-throughput, yet flexible single-crystal printing. Individual droplets of MOF precursor solutions are actuated over a matrix of hydrophilic-in-hydrophobic micropatterns for the controlled generation of femtoliter droplets. As such, thousands of monodisperse single MOF crystals are printed per second in a desired pattern, without the use of impractically expensive equipment. PMID- 22298247 TI - Super-resolution methods in MRI: can they improve the trade-off between resolution, signal-to-noise ratio, and acquisition time? AB - Improving the resolution in magnetic resonance imaging comes at the cost of either lower signal-to-noise ratio, longer acquisition time or both. This study investigates whether so-called super-resolution reconstruction methods can increase the resolution in the slice selection direction and, as such, are a viable alternative to direct high-resolution acquisition in terms of the signal to-noise ratio and acquisition time trade-offs. The performance of six super resolution reconstruction methods and direct high-resolution acquisitions was compared with respect to these trade-offs. The methods are based on iterative back-projection, algebraic reconstruction, and regularized least squares. The algorithms were applied to low-resolution data sets within which the images were rotated relative to each other. Quantitative experiments involved a computational phantom and a physical phantom containing structures of known dimensions. To visually validate the quantitative evaluations, qualitative experiments were performed, in which images of three different subjects (a phantom, an ex vivo rat knee, and a postmortem mouse) were acquired with different magnetic resonance imaging scanners. The results show that super-resolution reconstruction can indeed improve the resolution, signal-to-noise ratio and acquisition time trade offs compared with direct high-resolution acquisition. PMID- 22298248 TI - Dosimetric impacts of microgravity: an analysis of 5th, 50th and 95th percentile male and female astronauts. AB - Computational phantoms serve an important role in organ dosimetry and risk assessment performed at the National Aeronautics and Space Administration (NASA). A previous study investigated the impact on organ dose equivalents and effective doses from the use of the University of Florida hybrid adult male (UFHADM) and adult female (UFHADF) phantoms at differing height and weight percentiles versus those given by the two existing NASA phantoms, the computerized anatomical man (CAM) and female (CAF) (Bahadori et al 2011 Phys. Med. Biol. 56 1671-94). In the present study, the UFHADM and UFHADF phantoms of different body sizes were further altered to incorporate the effects of microgravity. Body self-shielding distributions are generated using the voxel-based ray tracer (VoBRaT), and the results are combined with depth dose data from the NASA codes BRYNTRN and HZETRN to yield organ dose equivalents and their rates for a variety of space radiation environments. It is found that while organ dose equivalents are indeed altered by the physiological effects ofmicrogravity, the magnitude of the change in overall risk (indicated by the effective dose) is minimal for the spectra and simplified shielding configurations considered. The results also indicate, however, that UFHADMand UFHADF could be useful in designing dose reduction strategies through optimized positioning of an astronaut during encounters with solar particle events. PMID- 22298249 TI - Gastroesophageal reflux disease and postlaryngectomy tracheoesophageal fistula. AB - The objective of this study is to evaluate the incidence of pathologic gastroesophageal reflux in laryngectomized patient with phonatory prosthesis, analyzing potential related problems and appraising, at the same time, the effectiveness of a therapeutic protocol. A retrospective study was conducted on 43 phonatory prosthesis patients who had problems with regard to recurrent tracheoesophageal granulations, the need of frequent prosthesis replacement, within a 3-month period, and unsatisfactory vocal results. Such patients underwent physical examination of the fistula region and of the neopharynx and were submitted to esophagogastroduodenoscopy. Moreover the group of patients underwent a therapeutic protocol and were re-evaluated posttreatment, examining fistula region both on the tracheal side and on the esophageal side through videolaryngostroboscopy. Of the 43 recruited patients 13 (30%) presented tracheoesophageal granulations, 20 (46.5%) unsatisfactory vocal results and 10 (23.5%) frequent prosthesis replacement, within a 3-month period, due to abnormal biofilm development. In particular, of the 13 patients who had recurrent granulations, the evaluation results revealed the presence of gastroesophageal reflux disease (GERD) in 6 cases (46%). In the group of patients presenting unsatisfactory vocal results GERD was shown in 13 cases (65%). In the third group of patients GERD was found in two cases (20%). The overall analysis of the data gathered, allowed to identify GERD in 21 (49%) of the 43 patients submitted to the study. The results posttreatment indicated, in the first group, the disappearance or a significant (>75%) volume reduction of such formation in five cases (38%, p = 0.002). In the second group an overall improvement in the quality of voice was displayed at least for 12 patients (60%, p = 0.0001). Finally in the last group an increase of the prosthesis life was recorded in four (40%, p = 0.05) of the ten patients who had the need of prosthesis replacement within 3 months. Also the 22 GERD negative cases (51%) underwent the treatment, therefore representing the control group, whose posttreatment results showed substantial modifications in just two cases (9%). The data obtained suggest a high degree of correlation between the presence of pathologic gastric reflux and the partial or total prosthesis failure. The introduction of a specific therapeutic protocol has allowed to improve the quality of prosthesis (QoP) in 22 of the 43 patients (p < 0.001) who had a pathologic condition of the fistula and of the prosthesis. PMID- 22298250 TI - Electronystagmographic analysis of caloric test parameters in vestibular disorders. AB - The electronystagmographical analysis of the eye movements provoked by caloric stimulation is an important method in the evaluation and topical diagnostic procedure of several vestibular lesions. The aim of the study was to compare the electronystagmographical results of caloric response in several vestibular disorders. The patients were divided into five groups: right and left unilateral and bilateral peripheral lesions, central vestibular dysfunction, and normal vestibular function. In the normal vestibular system group the average caloric nystagmus SPV in normal vestibular system was 17.4 degrees /s. In the peripheral lesion groups the average slow phase velocities are decreased in the affected side, as we expected. In the compensated vestibular lesion the average ASPV of caloric nystagmus is also decreased on the unaffected side. This might be caused by the effect of the central adaptive mechanisms. According to our observations, in central dysfunctions the average caloric ASPV and the spontaneous nystagmus ASPV is increased (25.0 degrees /s). This suggests that in central vestibular lesions the central inhibiting mechanisms of the caloric response are impaired. Our results show that electronystagmographical analysis of spontaneous and caloric nystagmus is very important in the evaluation of dizzy patients. PMID- 22298251 TI - Thyroid incidentalomas in FDG-PET/CT: prevalence and clinical impact. AB - To evaluate the prevalence of thyroid FDG-PET/CT incidentalomas and the risk of malignancy in focal findings. A retrospective study of 3,062 PET scans was performed between 05/2006 and 09/2009. Prevalence of thyroid incidentalomas, risk of malignancy and correlation between standard uptake value (SUV) and cancer risk were analysed. The overall prevalence of thyroid incidentalomas was 2.4%. 71% showed a focal and 29% a diffuse uptake. In the focal uptake group, the diagnosis was clarified in 79% with cytology/histology. In 23.8% of the patients with a focal uptake, a malignant lesion was found. Diffuse uptake was predominantly associated with autoimmune thyroiditis. There was no statistically significant difference in the SUVmax between benign and malignant focal lesions (p = 0.0982). Patients with incidental focal uptake in the thyroid during FDG-PET/CT bear a considerable risk of malignancy and should undergo cytologic clarification of the diagnosis. PMID- 22298252 TI - Severity of depression and anxiety in obstructive sleep apnea syndrome. AB - Obstructive sleep apnea (OSA) is a common sleep disorder which can result in mood problems. The aim of this study was to evaluate the severity of depression and anxiety symptoms as the most prevalent psychological disturbances present in different severity of OSA. We performed a cross-sectional study of 685 recently diagnosed sleep-disordered patients, over the age of 18, referred to Noor Sleep Lab from August 2008 to November 2010. The participants filled the Beck depression inventory-II (BDI-II) and the Beck anxiety inventory (BAI) to assess the depression and anxiety symptoms. We collected other characteristics of subjects such as age, sex, body mass index (BMI) and Epworth sleepiness scale (ESS). Apnea hypopnea index (AHI) was determined by an overnight polysomnography. Mean age of the participants was 47.63 years (SD 11.73). More than half of patient had some degrees of depression and anxiety. AHI showed no significant correlation with BDI (p = 0.105, r = -0.070) or BAI (p = 0.712, r = -0.016). Obesity was not either correlated with depression or anxiety (p = 0.18, r = 0.05). Nonetheless, ESS was weakly correlated with depression (p = 0.001, r = 0.148) and anxiety scores (p = 0.006, r = 0.120). BMI and ESS means were significantly higher in patients with severe OSA (p = 0.000). In comparison with men, the severity of depressive and anxiety symptoms was significantly higher in women (p = 0.000). In this cross-sectional study of patients with sleep problems, OSA was not associated with severity of depression and anxiety symptoms. PMID- 22298253 TI - Ultra-thin SiO2 layers on TiO2: improved photocatalysis by enhancing products' desorption. AB - A study on the photocatalytic degradation of contaminants (salicylic acid and stearic acid) on titanium dioxide films overcoated with a few monolayers of silica is presented herein. A rather uncommon situation was observed, where the presence of the thin silica layers decreased the degradation rate of stearic acid while increasing that of salicylic acid. The results were explained by addressing the effect in the presence of silica films on the desorption of the intermediate products formed in the degradation of salicylic acid. This finding, which may apply also to other aromatic compounds, may have implications on the design and operation of photocatalytic devices for indoor applications, since ultrathin layers of silica are known to be formed over time on the photocatalyst. An interesting effect of the thickness of the silica sub-nanometre layer on the degradation rate of salicylic acid was explained in terms of gradual changes in the isoelectric point. If optimized, this effect can be utilized to precisely control adsorption or desorption and accordingly to induce specificity in the photocatalytic degradation of contaminants. A methodology for preparing a molecularly imprinting photocatalyst with an inert ultrathin layer in between the imprinted sites was presented. It was found that overcoating the area in between the imprinted sites preserved the benevolent effect of imprinting. While at present the imprinting effect was moderate, there is a reason to believe that this effect can be improved considerably by controlling the type of inert overlayer. PMID- 22298254 TI - Up-regulation of hexokinaseII in myeloma cells: targeting myeloma cells with 3 bromopyruvate. AB - Hexokinase II (HKII), a key enzyme of glycolysis, is widely over-expressed in cancer cells. However, HKII levels and its roles in ATP production and ATP dependent cellular process have not been well studied in hematopoietic malignant cells including multiple myeloma (MM) cells.We demonstrate herein that HKII is constitutively over-expressed in MM cells. 3-bromopyruvate (3BrPA), an inhibitor of HKII, promptly and substantially suppresses ATP production and induces cell death in MM cells. Interestingly, cocultures with osteoclasts (OCs) but not bone marrow stromal cells (BMSCs) enhanced the phosphorylation of Akt along with an increase in HKII levels and lactate production in MM cells. The enhancement of HKII levels and lactate production in MM cells by OCs were mostly abrogated by the PI3K inhibitor LY294002, suggesting activation of glycolysis in MM cells by OCs via the PI3K-Akt-HKII pathway. Although BMSCs and OCs stimulate MM cell growth and survival, 3BrPA induces cell death in MM cells even in cocultures with OCs as well as BMSCs. Furthermore, 3BrPA was able to diminish ATP-dependent ABC transporter activity to restore drug retention in MM cells in the presence of OCs. These results may underpin possible clinical application of 3BrPA in patients with MM. PMID- 22298257 TI - Standards for connecting microfluidic devices? AB - The field of microfluidics is maturing slowly but steadily and new products are entering the market, showing a bewildering number of technologies and formats. This article states the need for standards for microfluidic interconnections, chip dimensions and a vocabulary. It also explains where and why those standards might be useful. A description of the ongoing standardization activities is given and the need for further work is explained. PMID- 22298255 TI - 3-Bromopyruvate: targets and outcomes. AB - The pyruvate mimetic 3-bromopyruvate (3-BP) is generally presented as an inhibitor of glycolysis and has shown remarkable efficacy in not only preventing tumor growth, but even eradicating existant tumors in animal studies. We here review reported molecular targets of 3-BP and suggest that the very range of possible targets, which pertain to the altered energy metabolism of tumor cells, contributes both to the efficacy and the tumor specificity of the drug. Its in vivo efficacy is suggested to be due to a combination of glycolytic and mitochondrial targets, as well as to secondary effects affecting the tumor microenvironment. The cytotoxicity of 3-BP is less due to pyruvate mimicry than to alkylation of, e.g., key thiols. Alkylation of DNA/RNA has not been reported. More research is warranted to better understand the pharmacokinetics of 3-BP, and its potential toxic effects to normal cells, in particular those that are highly ATP-/mitochondrion-dependent. PMID- 22298258 TI - Oligoether-strapped calix[4]pyrrole: an ion-pair receptor displaying cation dependent chloride anion transport. AB - A ditopic ion-pair receptor (1), which has tunable cation- and anion-binding sites, has been synthesized and characterized. Spectroscopic analyses provide support for the conclusion that receptor 1 binds fluoride and chloride anions strongly and forms stable 1:1 complexes ([1.F](-) and [1.Cl](-)) with appropriately chosen salts of these anions in acetonitrile. When the anion complexes of 1 were treated with alkali metal ions (Li(+), Na(+), K(+), Cs(+), as their perchlorate salts), ion-dependent interactions were observed that were found to depend on both the choice of added cation and the initially complexed anion. In the case of [1.F](-), no appreciable interaction with the K(+) ion was seen. On the other hand, when this complex was treated with Li(+) or Na(+) ions, decomplexation of the bound fluoride anion was observed. In contrast to what was seen with Li(+), Na(+), K(+), treating [1.F](-) with Cs(+) ions gave rise to a stable, host-separated ion-pair complex, [F.1.Cs], which contains the Cs(+) ion bound in the cup-like portion of the calix[4]pyrrole. Different complexation behavior was seen in the case of the chloride complex, [1.Cl](-). Here, no appreciable interaction was observed with Na(+) or K(+). In contrast, treating with Li(+) produces a tight ion-pair complex, [1.Li.Cl], in which the cation is bound to the crown moiety. In analogy to what was seen for [1.F](-), treatment of [1.Cl](-) with Cs(+) ions gives rise to a host-separated ion-pair complex, [Cl.1.Cs], in which the cation is bound to the cup of the calix[4]pyrrole. As inferred from liposomal model membrane transport studies, system 1 can act as an effective carrier for several chloride anion salts of Group 1 cations, operating through both symport (chloride+cation co-transport) and antiport (nitrate-for chloride exchange) mechanisms. This transport behavior stands in contrast to what is seen for simple octamethylcalix[4]pyrrole, which acts as an effective carrier for cesium chloride but does not operates through a nitrate-for-chloride anion exchange mechanism. PMID- 22298259 TI - The puzzle of generalized osteoarthritis (OA) -- is OA a systemic enthesopathy? PMID- 22298260 TI - Hematopoietic stem cell transplantation for systemic sclerosis: if you are confused, remember: "it is a matter of the heart". PMID- 22298261 TI - Guilty by association: platelet reactivity and inflammation in psoriatic arthritis. PMID- 22298262 TI - Osteitis condensans of the sternal manubrium and ossification of the costoclavicular ligaments. PMID- 22298263 TI - Prologue: 2010 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). AB - The 2010 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) was held in December 2010 in Miami Beach, Florida, USA, with attendance by rheumatologists, dermatologists, and representatives of biopharmaceutical companies and patient groups. In a training session that preceded the GRAPPA meeting, members served as faculty while rheumatology fellows and dermatology residents presented their original research. During the 2-day GRAPPA meeting, presentations included a review of composite measures for psoriatic arthritis (PsA) and psoriasis, updates on imaging in psoriatic disease (ultrasound and magnetic resonance imaging), a 3-part discussion of the definition of inflammatory musculoskeletal disease, a 4-part discussion of the status and path forward in psoriatic disease biomarker research, an update on comorbidities in psoriasis and PsA, and a review of global education and partnering opportunities. Introductions to the discussions at the GRAPPA 2010 meeting are included in this prologue. PMID- 22298264 TI - GRAPPA Trainees Symposium 2010: a report from the GRAPPA 2010 annual meeting. AB - At the 2010 annual meeting of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis), 24 trainees (rheumatology fellows and dermatology residents) engaged in research in psoriatic disease were invited to present their work at the Trainees Symposium, which preceded the GRAPPA meeting and was also attended by GRAPPA members and invited guests. Nineteen posters and 6 oral presentations were presented by the trainees, all of which are summarized here. PMID- 22298265 TI - Development of composite measures for psoriatic arthritis: a report from the GRAPPA 2010 annual meeting. AB - Composite disease outcome measures have been used in rheumatology for some time, but a disease-specific composite measure for psoriatic arthritis (PsA) has not yet been validated. Currently, instruments developed for use in rheumatoid arthritis are employed in PsA and include the American College of Rheumatology response criteria (ACR20, 50, and 70) and the Disease Activity Score for 28 and 44 joints (DAS28 and DAS44); however, these instruments do not cover the full spectrum of psoriatic disease. A composite measure is one way of incorporating an assessment of all relevant clinical outcomes into one single measure. By definition, it incorporates several dimensions of disease status, often by combining these different domains into a single score, which in the case of PsA includes joints, skin, entheses, dactylitis, and axial disease. New indices that combine these diverse clinical manifestations of PsA are under development and, in some cases, in the validation phase. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) established the GRAPPA Composite Exercise (GRACE) project to compare existing and emerging composite measures and to develop a new index. At the GRAPPA 2010 meeting, initial results from this project were presented, and existing and new candidate measures were compared. PMID- 22298266 TI - The ultrasound imaging module: a report from the GRAPPA 2010 annual meeting. AB - In a plenary session at the 2010 meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), the use of sonography for evaluating articular disease and enthesitis in psoriasis and psoriatic arthritis (PsA) was reviewed. Ultrasound can readily demonstrate signs of synovitis, erosions, and osteoproliferation. There is a need to develop ultrasound joint indices to evaluate and follow PsA longitudinally. Sonography is able to depict ultrastructural features of enthesitis, as well as increased vascularity. Sonographic signs of subclinical enthesitis in patients with psoriasis have been reported by 2 groups, 1 of which has reported limited longitudinal data that suggest baseline composite enthesitis scores may predict future risk of PsA. Although recent studies have studied mostly lower extremity entheses, further work is needed to clarify if other areas need to be included, especially within the framework of the synovial entheseal complex. The study design of the PREPARE (Prevalence of Psoriatic Arthritis in Adults with Psoriasis) trial was also presented. PMID- 22298267 TI - Magnetic resonance imaging in psoriatic arthritis -- update on current status and future perspectives: a report from the GRAPPA 2010 annual meeting. AB - The potential of magnetic resonance imaging (MRI) for use in clinical practice and research has gained increasing interest over the last decade. International collaborative initiatives from GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) and/or OMERACT (Outcome Measures in Rheumatology) may contribute to facilitating research, identifying appropriate areas for use, and reaching consensus on the optimal examination technique. Accordingly, GRAPPA, a primary driver of international research in psoriasis and psoriatic arthritis (PsA), has focused on the current use and future development of MRI and other modern imaging modalities in PsA. This review, presented at the GRAPPA 2010 annual meeting, describes the current status of MRI in PsA, with a focus on its use in diagnosis, monitoring, and prediction of the disease course and treatment response. Important areas for future research are also outlined. PMID- 22298268 TI - The need to define musculoskeletal inflammation: a report from the GRAPPA 2010 annual meeting. AB - Psoriatic arthritis (PsA) is a form of spondyloarthritis, a group of conditions that share a spectrum of components including arthritis, enthesitis, dactylitis, and spine inflammation. In PsA, however, the unpredictable, heterogeneous, and often insidious involvement of joints or juxtaarticular tendons and ligaments can sometimes make clinical recognition of the disease a challenge. Underrecognition of PsA may be due to the absence of a single sensitive and specific diagnostic measure. Although the ClASsification of Psoriatic ARthritis (CASPAR) criteria introduced in 2006 have improved disease classification, they are designed to be applied to cases already diagnosed with inflammatory arthritis. Therefore, in order for these criteria to be applied, the clinician is required to recognize the presence of inflammatory arthritis, enthesitis, or spondylitis. At the 2010 annual meeting of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis), the need to define inflammatory arthritis, enthesitis, dactylitis, and spondylitis, especially for nonrheumatologists, was discussed. Conclusions from breakout group discussions are summarized. PMID- 22298269 TI - Distinguishing inflammatory from noninflammatory arthritis, enthesitis, and dactylitis in psoriatic arthritis: a report from the GRAPPA 2010 annual meeting. AB - The most widely applied criteria for classifying psoriatic arthritis (PsA) are the CASPAR (ClASsification of Psoriatic ARthritis) criteria. A patient who fulfills the CASPAR criteria must have evidence of inflammatory arthritis, enthesitis, or spondylitis, and may have an inflammatory musculoskeletal component, dactylitis. Although the criteria were developed by rheumatologists, not all patients with PsA are seen by rheumatologists. Thus, it is important for clinicians such as dermatologists, primary care providers, physiatrists, and orthopedists, and patients themselves, to be able to recognize the presence of inflammatory musculoskeletal disease and distinguish it from degenerative or traumatic musculoskeletal disease. At their 2010 annual meeting, members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) discussed the steps they are taking to define the key variables that must be present to distinguish inflammatory arthritis, enthesitis, and dactylitis from degenerative, traumatic, mechanical, or infectious forms of these conditions. PMID- 22298270 TI - Inflammatory spinal disease in psoriatic arthritis: a report from the GRAPPA 2010 annual meeting. AB - Diagnosing axial disease in patients with psoriatic arthritis (PsA) has been largely dependent on identifying inflammatory back pain (IBP), which itself has been difficult to define. We review the criteria used to identify IBP in patients with ankylosing spondylitis (AS) and other forms of spondyloarthritis. Recently, the Ankylosing SpondyloArthritis International Society (ASAS) developed a list of clinical and radiographic criteria for identifying IBP in patients with AS. However, it is more difficult to identify IBP in patients with PsA because generally they have less pain than patients with rheumatoid arthritis or AS. Further, PsA patients may have clinical symptoms of pain but negative radiographs. It may be more useful to identify sacroiliitis or syndesmophytes by magnetic resonance imaging (MRI), since MRI identifies lesions in the sacroiliac joints and the spine much earlier than can be detected on radiographs. In summary, all patients with PsA should be assessed for axial involvement with history, physical examination, and imaging. Patients with psoriasis whose history includes onset of back pain before age 40 years, the presence of night pain, and improvement with exercise but not with rest, or who have limited neck or back mobility, should be referred to a rheumatologist. PMID- 22298271 TI - Psoriasis and psoriatic arthritis video project: an update from the 2010 GRAPPA annual meeting. AB - Changes in severity of psoriasis and psoriatic arthritis (PsA) are assessed in clinical trials by a variety of physical examination instruments. At the 2010 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members were updated on the development and availability of modules that teach these instruments. Web-based interactive multimedia presentations for psoriasis assessments have been completed, including modules for Psoriasis Area and Severity Index and Body Surface Area, 5-point and 6-point Physician Global Assessment, the original and modified Nail Psoriasis Severity Index, the Palmar-Plantar Pustular Psoriasis Area and Severity Index, and the Psoriasis Scalp Severity Index. Rheumatology modules will include assessment of tender and swollen joints, and evaluations of enthesitis, dactylitis, and axial disease. Each module will include the background and rationale for each tool, demonstration video of each examination, diagrams and photographs to emphasize teaching points, and an optional examination at the end. The rheumatology modules have been recorded but were not yet available for review at the meeting. The dermatology modules are currently in use by pharmaceutical and biotechnology companies engaged in research on treatments for psoriasis and PsA. The next phase of this project includes analysis of interobserver reliability, translation into languages other than English for international users, and other proposed studies. PMID- 22298272 TI - Strategies for biomarker development in psoriatic disease: a report from the GRAPPA 2010 annual meeting. AB - Psoriatic disease includes psoriasis and associated comorbidities (arthritis, uveitis, inflammatory bowel disease, cardiovascular disease, metabolic syndrome, and anxiety/depression) and is remarkably diverse in disease presentation and course. The marked heterogeneity of musculoskeletal involvement in psoriatic arthritis (PsA) presents major challenges to clinicians regarding diagnosis, risk stratification, and management. Members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) have begun collaborative efforts to develop biomarkers that can assist in the diagnosis and management of patients with psoriasis and related comorbidities. This brief review provides a rationale for biomarker research in PsA, consideration of types and sources of biomarkers, and examples of important biomarker studies in PsA, followed by a review of trial designs for biomarker research and a discussion of potential funding sources. PMID- 22298273 TI - Update on biomarkers in psoriatic arthritis: a report from the GRAPPA 2010 annual meeting. AB - Biomarkers may be used to screen patients with psoriasis for psoriatic arthritis (PsA) and to assess disease activity and severity. Candidate biomarkers should fulfil the key features of the OMERACT (Outcome Measures in Rheumatology) filter, that is, truth, discrimination, and feasibility. A number of biomarkers are currently being investigated in psoriatic disease for important clinical outcomes. Serum high sensitivity C-reactive protein, cartilage oligomeric matrix protein, interleukin 6 (IL-6), osteoprotegerin, matrix metalloprotease-3 (MMP-3), and the ratio of C-propeptide of type II collagen (CPII) to collagen fragment neoepitopes Col2-3/4 (long mono) (C2C) show promise as serum biomarkers that distinguish subjects with PsA from those with psoriasis alone. Serum MMP-3 and melanoma inhibitory activity, synovial fluid IL-1, IL-1 receptor-alpha, IL-6, IL 8, and chemokine CCL3 and synovial tissue CD3-positive T cells may prove useful as biomarkers of PsA activity. Circulating osteoclast precursors, Dickkopf-1, macrophage colony stimulating factor, receptor activator of nuclear factor-kappaB ligand, and bone alkaline phosphatase are strong candidates as biomarkers of radiographic change. Prospective studies to identify biomarkers for psoriatic disease are high on the research agenda of the Group for Research and Assessment of Psoriasis and PsA. PMID- 22298275 TI - The path forward to biomarker discovery in psoriatic disease: a report from the GRAPPA 2010 annual meeting. AB - At the 2010 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), wide-ranging discussions were held regarding biomarker research in psoriatic disease. Consensus was reached on 2 areas of priority: (1) the study of soluble biomarkers of radiographic progression in psoriatic arthritis (PsA); and (2) the analysis of comorbidity biomarkers, specifically cardiovascular and articular, in a psoriasis inception cohort. For each of these areas, rigorous definition of the clinical phenotype of PsA will be essential. To date, 2 instruments have been identified to define the phenotype: the ClASsification of Psoriatic ARthritis criteria and various screening questionnaires. In this overview, we discuss the challenges of the clinical phenotype of PsA and review GRAPPA plans for developing a research program for biomarker discovery. PMID- 22298274 TI - Genetics of psoriasis and psoriatic arthritis: a report from the GRAPPA 2010 annual meeting. AB - Psoriasis vulgaris (PsV) and psoriatic arthritis (PsA) are interrelated disorders, PsA representing a disease within a disease. From an epidemiological perspective, the genetic contributions of PsV and PsA are now well documented. HLA-C is firmly established as a PsV/PsA gene, with HLA-Cw*0602 as a major risk allele. Fine-mapping studies within the MHC region in PsV and PsA have identified novel loci that are independent of the HLA-Cw6 allele. Recent genome-wide association scans have led to a substantial increase in the number of candidate genes reaching genome-wide significance in PsV and PsA cohorts. Most of these genes can be grouped into an integrated pathogenic model of PsV/psoriatic disease comprising distinct signaling networks affecting skin barrier function (LCE3, DEFB4, GJB2), innate immune responses involving nuclear factor-kappaB and interferon signaling (TNFAIP3, TNIP1, NFKBIA, REL, FBXL19, TYK2, NOS2), and adaptive immune responses involving CD8 T lymphocytes and interleukin 23 (IL 23)/IL-17-mediated lymphocyte signaling (HLA-C, IL12B, IL23R, IL23A, TRAF3IP2, ERAP1). Further development of a global genetic risk score and inclusion of potential gene/gene and gene/environment interactions will likely enhance the predictive value of recently identified genetic variants. PMID- 22298276 TI - Comorbidities of psoriatic arthritis -- metabolic syndrome and prevention: a report from the GRAPPA 2010 annual meeting. AB - Psoriatic arthritis (PsA) is associated with serious comorbidities such as increased cardiovascular risk, hypertension, depression, and reduced quality of life. Patients with psoriasis have been observed to have an increased incidence of metabolic syndrome compared with the general population; recently, this has also been observed in patients with PsA. This review focuses on the comorbidities associated with PsA, with an emphasis on risks of coronary artery disease and metabolic syndrome. We also discuss the development of a comprehensive approach for the management of comorbidities of PsA. The review summarizes a presentation at the 2010 annual meeting of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis). PMID- 22298277 TI - Epidemiology and potential pathomechanisms of cardiovascular comorbidities in psoriasis: a report from the GRAPPA 2010 annual meeting. AB - There is increasing awareness that psoriasis is more than "skin deep." Several recent reviews focused on biomarkers have indicated the systemic dimension of psoriasis and the comorbidity that psoriasis shares with other chronic inflammatory diseases. Of emerging significance is the relationship to cardiovascular disease, which contributes substantially to patients' increased mortality. This article examines currently available evidence favoring the concept of a causal link between psoriasis and cardiovascular disease, and summarizes a report represented at the 2010 Annual Meeting of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis). PMID- 22298278 TI - Global partnering opportunities and challenges of psoriasis and psoriatic arthritis in Latin America: a report from the GRAPPA 2010 annual meeting. AB - Documenting the disease burden of psoriasis and psoriatic arthritis (PsA) in Central and South America is difficult. The most conclusive data have come from the Iberoamerican Registry of Spondyloarthritis (RESPONDIA), which registered patients with a diagnosis of spondyloarthritis in a multinational, multicenter (Argentina, Brazil, Costa Rica, Chile, Mexico, Peru, Uruguay, Venezuela, Spain, and Portugal) cross-sectional study conducted between 2006 and 2007. Compared with elsewhere in the Western world, patients with PsA from RESPONDIA were older at study visit, at onset of symptoms, and at diagnosis of spondyloarthritis (SpA); had longer mean disease duration from onset of symptoms to diagnosis; and were more likely to have dactylitis, nail involvement, enthesitis, and peripheral arthritis in lower and upper extremities. It is critical to understand the biologic basis, estimate the disease burden, and determine the clinical treatment of PsA in Latin America. The Group for Research and Assessment of Psoriasis and PsA (GRAPPA) has an increasing number of members from this region. In a coordinated effort, GRAPPA, the Latin American Psoriasis and PsA Society (LAPPAS), and the Pan American League of Associations for Rheumatology (PANLAR) are supporting clinician researchers with educational initiatives in Latin America to understand these conditions. PMID- 22298279 TI - Subendocardial ischemia and myocarditis in systemic lupus erythematosus detected by cardiac magnetic resonance imaging. PMID- 22298280 TI - Intravenous immunoglobulin expands regulatory T cells in autoimmune rheumatic disease. PMID- 22298281 TI - Doppler imaging and histology of the synovium. PMID- 22298283 TI - Treatment of Neurocritical Care Emergencies in Pregnancy. AB - OPINION STATEMENT: Neurologic emergencies are a major cause of morbidity and mortality in pregnant women. In part because the patient population is young, the nihilistic approach that often accompanies neurologically devastating disorders in other contexts is largely absent. A number of studies have demonstrated improved patient outcomes in the setting of aggressive care delivered by neurointensivists in a specialty-specific environment. It stands to reason that young, pregnant women who suffer from neurologically devastating disorders and who have a wide range of prognosis may also benefit from such specialized care. Close collaboration between obstetricians and neurointensivists is critical in this context. A number of unique considerations in diagnosis and management present dilemmas in the context of pregnancy, such as radiation dose from diagnostic neuroimaging, choice of pharmacotherapy for seizures, anticoagulation, and the method of delivery in the context of cerebral mass lesions and elevated intracranial pressure. Patients and their physicians are often faced with the additional challenge of balancing the relative risks and benefits of the impact of a management approach on both mother and fetus. In general, this balance tends to favor the interests of the mother, but the impact on the fetus becomes more relevant over the course of the pregnancy, especially in the third trimester. A low threshold for admission to an intensive care unit (ideally one that specializes in neurointensive care) should be used for pregnant patients. Because of the limited information regarding long-term outcomes in this population, rigid prognosis formation and early care limitations should be deferred in the immediate period. After the patient is stabilized and a plan has been charted for the remainder of the pregnancy, every effort should be made to engage patients in aggressive, urgent neurologic rehabilitation. PMID- 22298284 TI - Anti-galvanic reduction of thiolate-protected gold and silver nanoparticles. PMID- 22298285 TI - Multiscale simulation of small peptides: consistent conformational sampling in atomistic and coarse-grained models. AB - A bottom-up coarse-graining procedure for peptides in aqueous solution is presented, where the interactions in the coarse-grained (CG) model are determined such that the CG peptide samples conformations according to a high-resolution (atomistic) model. It is shown that important aspects of conformational sampling, such as correlated degrees of freedom (DOF) which play an important role in secondary structure formation, can be reproduced in the CG description. In some cases, microscopic structural/conformational details are lost in the coarse graining process. We show that these "lost" properties can be recovered in a backmapping procedure which reintroduces atomistic DOF into CG structures - as long as the overall conformational sampling of the molecule is correctly represented in the CG level of resolution. Thus, it is possible to link an existing all-atom model of a biomolecular system with a CG description such that after inverse mapping one can recover structures at high resolution with the correctly sampled (according to the atomistic model) conformational properties. PMID- 22298287 TI - Psychometric properties and differential explanation of a short measure of effort reward imbalance at work: a study of industrial workers in Germany. AB - BACKGROUND: We test the psychometric properties of a short version of the Effort Reward Imbalance (ERI) questionnaire in addition to testing an interaction term of this model's main components on health functioning. METHODS: A self administered survey was conducted in a sample of 2,738 industrial workers (77% men with mean age 41.6 years) from a large manufacturing company in Southern Germany. The internal consistency reliability, structural validity, and criterion validity were analyzed. RESULTS: Satisfactory internal consistencies of the three scales: "Effort", "reward", and "overcommitment", were obtained (Cronbach's alpha coefficients 0.77, 0.82, and 0.83, respectively). Confirmatory factor analysis showed a good model fit of the data with the theoretical structure (AGFI = 0.94, RMSEA = 0.060). Evidence of criterion validity was demonstrated. Importantly, a significant synergistic interaction effect of ERI and overcommitment on poor mental health functioning was observed (odds ratio 6.74 (95% CI 5.32-8.52); synergy index 1.78 (95% CI 1.25-2.55)). CONCLUSIONS: This short version of the ERI questionnaire is a reliable and valid tool for epidemiological research on occupational health. PMID- 22298286 TI - Hip pain while using lower extremity joints and sleep disturbances in elderly white women: results from a cross-sectional analysis. AB - OBJECTIVE: To evaluate sleep quality in women with hip pain due to daily activities involving the lower extremity joints. METHODS: We evaluated the association of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) hip pain severity score with objective sleep measures obtained by wrist actigraphy in 2,225 white women >= 65 years of age enrolled in the Study of Osteoporotic Fractures. RESULTS: Women had an increased odds of spending >= 90 minutes awake after sleep onset (odds ratio [OR] 1.28, 95% confidence interval [95% CI] 1.11-1.50) for every 5-point increase in hip pain score after adjustment for all covariates. Hip pain when sitting or lying was the strongest predictor of sleep fragmentation (OR 2.0, 95% CI 1.47-2.73); however, standing pain was associated with a higher number of awake minutes in bed scored from sleep onset to the end of the last sleep episode, independent of pain while in bed (OR 1.41, 95% CI 1.07-2.01). Sleep disturbances increased significantly after the first 2 hours of sleep in women with severe hip pain compared to those without hip pain (mean +/- SD 1.4 +/- 0.47 minutes per hour of sleep; P < 0.003). Similar associations were observed for long wake episodes >5 minutes. There were no associations between daytime napping, sleep latency, sleep efficiency, and total sleep minutes and WOMAC hip pain. CONCLUSION: Fragmented sleep was greater in women with hip pain compared to those without hip pain; however, fragmented sleep in women with severe hip pain compared to those without hip pain was unchanged until after the first 2 hours of sleep. Further investigations into pain medications wearing off over time or the prolonged periods of inactivity decreasing the pain threshold are warranted. PMID- 22298288 TI - Polar aprotic modifiers for chromatographic separation and back-exchange reduction for protein hydrogen/deuterium exchange monitored by Fourier transform ion cyclotron resonance mass spectrometry. AB - Hydrogen/deuterium exchange monitored by mass spectrometry is an important non perturbing tool to study protein structure and protein-protein interactions. However, water in the reversed-phase liquid chromatography mobile phase leads to back-exchange of D for H during chromatographic separation of proteolytic peptides following H/D exchange, resulting in incorrect identification of fast exchanging hydrogens as unexchanged hydrogens. Previously, fast high-performance liquid chromatography (HPLC) and supercritical fluid chromatography have been shown to decrease back-exchange. Here, we show that replacement of up to 40% of the water in the LC mobile phase by the modifiers, dimethylformamide (DMF) and N methylpyrrolidone (NMP) (i.e., polar organic modifiers that lack rapid exchanging hydrogens), significantly reduces back-exchange. On-line LC micro-ESI FT-ICR MS resolves overlapped proteolytic peptide isotopic distributions, allowing for quantitative determination of the extent of back-exchange. The DMF modified solvent composition also improves chromatographic separation while reducing back exchange relative to conventional solvent. PMID- 22298289 TI - Increased protein structural resolution from diethylpyrocarbonate-based covalent labeling and mass spectrometric detection. AB - Covalent labeling and mass spectrometry are seeing increased use together as a way to obtain insight into the 3-dimensional structure of proteins and protein complexes. Several amino acid specific (e.g., diethylpyrocarbonate) and non specific (e.g., hydroxyl radicals) labeling reagents are available for this purpose. Diethylpyrocarbonate (DEPC) is a promising labeling reagent because it can potentially probe up to 30% of the residues in the average protein and gives only one reaction product, thereby facilitating mass spectrometric analysis. It was recently reported, though, that DEPC modifications are labile for some amino acids. Here, we show that label loss is more significant and widespread than previously thought, especially for Ser, Thr, Tyr, and His residues, when relatively long protein digestion times are used. Such label loss ultimately decreases the amount of protein structural information that is obtainable with this reagent. We find, however, that the number of DEPC modified residues and, thus, protein structural information, can be significantly increased by decreasing the time between the covalent labeling reaction and the mass spectrometric analysis. This is most effectively accomplished using short (e.g., 2 h) proteolytic digestions with enzymes such as immobilized chymotrypsin or Glu C rather than using methods (e.g., microwave or ultrasonic irradiation) that accelerate proteolysis in other ways. Using short digestion times, we show that the percentage of solvent accessible residues that can be modified by DEPC increases from 44% to 67% for cytochrome c, 35% to 81% for myoglobin, and 76% to 95% for beta-2-microglobulin. In effect, these increased numbers of modified residues improve the protein structural resolution available from this covalent labeling method. Compared with typical overnight digestion conditions, the short digestion times decrease the average distance between modified residues from 11 to 7 A for myoglobin, 13 to 10 A for cytochrome c, and 9 to 8 A for beta-2 microglobulin. PMID- 22298290 TI - Retention time alignment of LC/MS data by a divide-and-conquer algorithm. AB - Liquid chromatography-mass spectrometry (LC/MS) has become the method of choice for characterizing complex mixtures. These analyses often involve quantitative comparison of components in multiple samples. To achieve automated sample comparison, the components of interest must be detected and identified, and their retention times aligned and peak areas calculated. This article describes a simple pairwise iterative retention time alignment algorithm, based on the divide and-conquer approach, for alignment of ion features detected in LC/MS experiments. In this iterative algorithm, ion features in the sample run are first aligned with features in the reference run by applying a single constant shift of retention time. The sample chromatogram is then divided into two shorter chromatograms, which are aligned to the reference chromatogram the same way. Each shorter chromatogram is further divided into even shorter chromatograms. This process continues until each chromatogram is sufficiently narrow so that ion features within it have a similar retention time shift. In six pairwise LC/MS alignment examples containing a total of 6507 confirmed true corresponding feature pairs with retention time shifts up to five peak widths, the algorithm successfully aligned these features with an error rate of 0.2%. The alignment algorithm is demonstrated to be fast, robust, fully automatic, and superior to other algorithms. After alignment and gap-filling of detected ion features, their abundances can be tabulated for direct comparison between samples. PMID- 22298291 TI - Two-dimensional polymer as a mask for surface nanopatterning. AB - NaCl islands are used as a sacrificial layer to selectively deposit a boronic acid based two-dimensional polymer. The nanostructured polymer layer can be used as a negative mask to create Fe islands in a nanolithography mimicking process. PMID- 22298292 TI - Profiling of Epstein-Barr virus-encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs. PMID- 22298293 TI - A novel in vivo method for lung segment movement tracking. AB - Knowledge about lung movement in health and disease is sparse. Current evaluation methods, such as CT, MRI and external view have significant limitations. To study respiratory movement for image guided tumour diagnostics and respiratory physiology, we needed a method that overcomes these limitations.We fitted balloon catheters with electromagnetic sensors, and placed them in lung lobes of ventilated pigs. The sensors sensed their position at 40 Hz in an electromagnetic tracking field with a precision of ~0.5 mm. The method was evaluated by recording sensor movement in different body positions and at different tidal volumes. No 'gold standard' exists for lung segment tracking, so our results were compared to 'common knowledge'. The sensors were easily placed, showed no clinically relevant position drift and yielded sub-millimetre accuracy. Our measurements fit 'common knowledge', as increased ventilation volume increased respiratory movement, and the right lung moved significantly less in the right than the left lateral position. The novel method for tracking lung segment movements during respiration was easy to implement and yielded high spatial and temporal resolution, and the equipment parts are reusable. It is easy to implement as a research tool for lung physiology, navigated bronchoscopy and radiation therapy. PMID- 22298294 TI - Expressed sequences and polymorphisms in rohu carp (Labeo rohita, Hamilton) revealed by mRNA-seq. AB - Expressed genes and polymorphisms were identified in lines of rohu Labeo rohita selected for resistance or susceptibility to Aeromonas hydrophila, an important bacterial pathogen causing aeromoniasis. All animals were grown in a common environment and RNA from ten individuals from each line pooled for Illumina mRNA seq. De novo transcriptome assembly produced 137,629 contigs with 40* average coverage.Forty-four percent of the assembled sequences were annotated with gene names and ontology terms. Of these, 3,419 were assigned biological process terms related to "stress response" and 1,939 "immune system". Twenty-six contigs containing 38 single nucleotide polymorphisms (SNPs) were found to map to the Cyprinus carpio mitochondrial genome and over 26,000 putative SNPs and 1,700 microsatellite loci were detected. Seventeen percent of the 100 transcripts with coverage data most indicative of higher-fold expression(>5.6 fold) in the resistant line pool showed homology to major histocompatibility (MH), heat shock proteins (HSP)30, 70 and 90, glycoproteins or serum lectin genes with putative functions affecting immune response. Forty-one percent of these 100 transcripts showed no or low homology to known genes. Of the SNPs identified, 96 showing the highest allele frequency differences between susceptible and resistant line fish included transcripts with homology to MH class I and galactoside-binding soluble lectin, also with putative functions affecting innate and acquired immune response. A comprehensive sequence resource for L. rohita, including annotated microsatellites and SNPs from a mixture of A. hydrophila-susceptible and resistant individuals, was created for subsequent experiments aiming to identify genes associated with A. hydrophila resistance. PMID- 22298295 TI - Influence of foot orientation on the appearance and quantification of 1H magnetic resonance muscle spectra obtained from the soleus and the vastus lateralis. AB - Muscle (1)H magnetic resonance spectroscopy noninvasively measures intramyocellular lipid levels, which correlate with obesity, insulin resistance, and type 2 diabetes. The appearance of muscle magnetic resonance spectra is influenced by bulk magnetic susceptibility and residual dipolar couplings which depend on the angle between the muscle fibers and the main magnetic field. This study used a 4 T magnet to examine the influence of foot orientation on the appearance and quantification of muscle magnetic resonance spectra from the soleus and the vastus lateralis. For each individual, intramyocellular lipid, extramyocellular lipid, and creatine concentrations were quantified in the soleus and the vastus lateralis during one session. Foot orientation was found to influence the appearance of muscle spectra from the soleus but not from the vastus lateralis. It was concluded that quantifying intramyocellular lipid by the standard LCModel using a water reference may be more appropriate than using a creatine reference in the presence of residual dipolar couplings. PMID- 22298297 TI - Selective conversion of cellobiose and cellulose into gluconic acid in water in the presence of oxygen, catalyzed by polyoxometalate-supported gold nanoparticles. AB - Gold nanoparticles loaded onto Keggin-type insoluble polyoxometalates (Cs(x)H(3 x)PW(12)O(40)) showed superior catalytic performances for the direct conversion of cellobiose into gluconic acid in water in the presence of O(2). The selectivity of Au/Cs(x)H(3-x)PW(12)O(40) for gluconic acid was significantly higher than those of Au catalysts loaded onto typical metal oxides (e.g., SiO(2), Al(2)O(3), and TiO(2)), carbon nanotubes, and zeolites (H-ZSM-5 and HY). The acidity of polyoxometalates and the mean-size of the Au nanoparticles were the key factors in the catalytic conversion of cellobiose into gluconic acid. The stronger acidity of polyoxometalates not only favored the conversion of cellobiose but also resulted in higher selectivity of gluconic acid by facilitating desorption and inhibiting its further degradation. On the other hand, the smaller Au nanoparticles accelerated the oxidation of glucose (an intermediate) into gluconic acid, thereby leading to increases both in the conversion of cellobiose and in the selectivity of gluconic acid. The Au/Cs(x)H(3 x)PW(12)O(40) system also catalyzed the conversion of cellulose into gluconic acid with good efficiency, but it could not be used repeatedly owing to the leaching of a H(+)-rich hydrophilic moiety over long-term hydrothermal reactions. We have demonstrated that the combination of H(3)PW(12)O(40) and Au/Cs(3.0)PW(12)O(40) afforded excellent yields of gluconic acid (about 85%, 418 K, 11 h), and the deactivation of the recovered H(3)PW(12)O(40) Au/Cs(3.0)PW(12)O(40) catalyst was not serious during repeated use. PMID- 22298298 TI - Arylpiperazine dopamineric ligands protect neuroblastoma cells from nitric oxide (NO)-induced mitochondrial damage and apoptosis. AB - The protective ability of novel arylpiperazine-based dopaminergic ligands against nitric oxide (NO)-mediated neurotoxicity is investigated. The most potent neuroprotective arylpiperazine identified during the study was N-{4-[2-(4-phenyl piperazin-1-yl)ethyl]-phenyl}picolinamide, which protected SH-SY5Y human neuron like cells from the proapoptotic effect of NO donor sodium nitroprusside (SNP) by decreasing oxidative stress, mitochondrial membrane depolarization, caspase activation and subsequent phosphatydilserine externalization/DNA fragmentation. The protective effect was associated with the inhibition of proapoptotic (JNK, ERK, AMPK) and activation of antiapoptotic (Akt) signaling pathways, in the absence of interference with intracellular NO accumulation. The neuroprotective action of arylpiperazines was shown to be independent of dopamine receptor binding, as it was not affected by the high-affinity D1/D2 receptor blocker butaclamol. These results reported support the further study of arylpiperazines as potential neuroprotective agents. PMID- 22298299 TI - In-cell solid-state NMR as a tool to study proteins in large complexes. AB - A major limitation of solution NMR is molecular tumbling, which is often too slow for detection. Here we demonstrate that solid-state NMR spectroscopy in combination with flash freezing of cells can be used to detect proteins in the cellular environment and provides information on backbone chemical shifts. PMID- 22298300 TI - Iterative asymmetric allylic substitutions: syn- and anti-1,2-diols through catalyst control. AB - A copper-catalyzed asymmetric allylic boronation (AAB) gives access to syn- and anti-1,2-diols. The method facilitates an iterative strategy for the preparation of polyols, such as the fully differentiated L-ribo-tetrol and protected D arabino-tetrol. P=protecting group. PMID- 22298301 TI - Recovery of a patient from clinical rabies--California, 2011. AB - In May 2011, a girl aged 8 years from a rural county in California was brought to a local emergency department (ED) with a 1-week history of progressive sore throat, difficulty swallowing, and weakness. After she developed flaccid paralysis and encephalitis, rabies was diagnosed based on 1) detection of rabies virus-specific antibodies in serum and cerebrospinal fluid (CSF), 2) a compatible clinical syndrome in the patient, and 3) absence of a likely alternative diagnosis. The patient received advanced supportive care, including treatment with therapeutic coma. She was successfully extubated after 15 days and discharged from the hospital 37 days later to continue rehabilitation therapy as an outpatient. The public health investigation identified contact with free roaming, unvaccinated cats at the patient's school as a possible source of infection. Several of these cats were collected from the school and remained healthy while under observation, but at least one was lost to follow-up. A total of 27 persons received rabies postexposure prophylaxis (PEP) for potential exposures to the patient's saliva. No further cases of rabies associated with this case have been identified. Rabies prevention efforts should highlight the importance of domestic animal vaccination, avoidance of wildlife and unvaccinated animals, and prompt PEP after an exposure. PMID- 22298302 TI - Adult vaccination coverage--United States, 2010. AB - Immunizations are recommended throughout life to prevent infectious diseases and their sequelae. Adult coverage, however, remains low for most routinely recommended vaccines and well below Healthy People 2020 targets. In October 2011, the Advisory Committee on Immunization Practices (ACIP) approved the adult immunization schedule for 2012. Apart from influenza vaccination, which is now recommended for all adults, other adult vaccines target different populations based on age, certain medical conditions, behavioral risk factors (e.g., injection drug use), occupation, travel, and other indications. To assess adult (>=19 years) vaccination coverage for select vaccines, CDC analyzed data from the 2010 National Health Interview Survey (NHIS). This report summarizes the results of that analysis for pneumococcal, hepatitis A, hepatitis B, herpes zoster (shingles), and human papillomavirus (HPV) vaccines, as well as tetanus antigen containing vaccines (including tetanus, diphtheria, and acellular pertussis vaccine [Tdap]), by selected characteristics (age, vaccination target group status, and race/ethnicity). Influenza vaccination coverage estimates for the 2010-11 influenza season have been published separately. Compared with results of the 2009 NHIS survey, increases in coverage were observed only for Tdap vaccination for persons aged 19-64 years (1.6 percentage point increase to 8.2%), zoster vaccination among persons aged >=60 years (4.4 percentage point increase to 14.4%), and >=1 dose HPV vaccination in women aged 19-26 years (3.6 percentage point increase to 20.7%); coverage for the other vaccines was unchanged at <70%. These data indicate only limited recent improvements in vaccination coverage among adults in the United States. Substantial increases are needed to reduce the occurrence of vaccine-preventable diseases among adults. PMID- 22298303 TI - Progress in global measles control, 2000-2010. AB - In 1980, before widespread global use of measles vaccine, an estimated 2.6 million measles deaths occurred worldwide. In 2001, to accelerate the reduction in measles cases achieved by vaccination, the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) developed a strategy to deliver 2 doses of measles-containing vaccine (MCV) to all children through routine services and supplementary immunization activities (SIAs) and improved disease surveillance. After implementation of this strategy, the estimated number of annual measles deaths worldwide decreased from 733,000 in 2000 to 164,000 in 2008. In 2010, the World Health Assembly endorsed the following measles objectives for 2015: 1) raise routine coverage with the first dose of MCV (MCV1) for children aged 1 year to >=90% nationally and >=80% in every district or equivalent administrative unit, 2) reduce and maintain annual measles incidence at <5 cases per million, and 3) reduce measles mortality by >=95% from the 2000 estimate. During 2000-2010, global MCV1 coverage increased from 72% to 85% with approximately 1 billion children vaccinated during measles SIAs. Reported measles cases decreased from 2000 to 2008, remained stable in 2009, and increased in 2010. By the end of 2010, 40% of countries still had not met the incidence target of <5 cases per million. Key challenges must be overcome to meet the 2015 objectives, including 1) declining political and financial commitments to measles control, 2) failure to reach uniform high coverage with 2 doses of MCV through routine services or SIAs, and 3) inadequate monitoring subnationally of coverage with the first and second dose of MCV to guide interventions to increase coverage. PMID- 22298304 TI - Notes from the field: outbreak of salmonellosis associated with pet turtle exposures--United States, 2011. AB - CDC is collaborating with the Pennsylvania State Health Department in an ongoing investigation of an outbreak of human Salmonella enterica serotype Paratyphi B var. L (+) tartrate + infections associated with pet turtle exposures. Turtles have long been recognized as sources of human Salmonella infections and are a particular risk to young children. Although the sale or distribution of small turtles (those with carapace lengths <4 inches [<10.2 cm]) has been prohibited in the United States since 1975 (with exceptions for scientific or educational purposes), they are still available for illegal purchase through transient vendors on the street, at flea markets, and at fairs. PMID- 22298306 TI - Endobronchial ultrasound-guided transbronchial needle aspiration diagnosis of mediastinal lymph node metastasis of mucinous adenocarcinoma: arborizing stromal meshwork fragments as a diagnostic clue. AB - Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) is a reliable and accurate method for the diagnosis of mediastinal metastases in patients with pulmonary and extrathoracic neoplasms. We report the cytopathologic findings of a case of metastatic signet-ring cell carcinoma with abundant extracellular mucin production in the mediastinal lymph nodes of a 41-year-old woman, who presented with nausea, abdominal pain, and weight loss. Imaging studies showed a renal mass, numerous lung nodules, and mediastinal and retroperitoneal lymphadenopathy. EBUS-TBNA of level 4R and 7 lymph nodes showed abundant, thick, "clean" mucus with entrapped ciliated bronchial cells, rare histiocytes, and fragments of cartilage. No neoplastic cells could be identified in Diff-Quik(r)-stained smears during the rapid on-site evaluation, but rare signet-ring cells were identified in the Papanicolaou-stained smears and cellblock sections. A distinctive feature of the aspirates was the presence of large branching (arborizing), "spidery" stromal fiber meshwork fragments. These stained metachromatically (magenta) with Romanowsky-type stains and cyanophilic to orangeophilic with Papanicolaou stains and showed occasional attached bland spindle cells, but had no capillary lumina or CD31-staining endothelial cells. The tumor cells were strongly and diffusely positive for CEA, CDX2, CK7, CK20, and MUC2, supporting the diagnosis of a metastatic signet-ring cell adenocarcinoma, most likely of gastrointestinal origin. We believe that the presence of the large spidery stromal fiber fragments is a useful clue to the presence of a mucinous neoplasm in EBUS-TBNA and allows the differentiation of the neoplastic mucus from contaminating endobronchial mucus. PMID- 22298308 TI - Respiratory health status of children from two different air pollution exposure settings of Sri Lanka: a cross-sectional study. AB - BACKGROUND: Health effects due to air pollution is becoming a major public health problem with growing traffic congestion and establishment of small- to medium scale industries with poor emission controls in urban cities of Sri Lanka. METHODS: Respiratory health status of 7- to 10-year-old children in two settings (urban and semi-urban) was assessed using standard questionnaires. Information on socio-demographic characteristics and potential determinants of both outdoor and indoor air pollutants exposure levels were also obtained. The respiratory health status of children in the two settings was compared. RESULTS: We found that children from the urban setting had a significantly higher prevalence of wheezing within the last 12 months as compared to children from the semi-urban setting (adjusted OR = 2.02; 95% CI = 1.13-3.59). Indoor cooking with unclean fuels was a risk factor for wheezing independent of the area of residence (adjusted OR = 1.57; 95% CI = 1.01-2.46). CONCLUSIONS: Poor indoor air quality was a major determinant of wheezing for the overall study group. Children from urban areas of Sri Lanka have poorer respiratory health status as compared to children from semi urban areas. Besides poor outdoor air quality, this difference may also be due to other unexplored factors which may differ between urban and semi-urban areas in Sri Lanka. PMID- 22298309 TI - Multiple keys for a single lock: the unusual structural plasticity of the nucleotidyltransferase (4')/kanamycin complex. AB - The most common mode of bacterial resistance to aminoglycoside antibiotics is the enzyme-catalysed chemical modification of the drug. Over the last two decades, significant efforts in medicinal chemistry have been focused on the design of non inactivable antibiotics. Unfortunately, this strategy has met with limited success on account of the remarkably wide substrate specificity of aminoglycoside modifying enzymes. To understand the mechanisms behind substrate promiscuity, we have performed a comprehensive experimental and theoretical analysis of the molecular-recognition processes that lead to antibiotic inactivation by Staphylococcus aureus nucleotidyltransferase 4'(ANT(4')), a clinically relevant protein. According to our results, the ability of this enzyme to inactivate structurally diverse polycationic molecules relies on three specific features of the catalytic region. First, the dominant role of electrostatics in aminoglycoside recognition, in combination with the significant extension of the enzyme anionic regions, confers to the protein/antibiotic complex a highly dynamic character. The motion deduced for the bound antibiotic seem to be essential for the enzyme action and probably provide a mechanism to explore alternative drug inactivation modes. Second, the nucleotide recognition is exclusively mediated by the inorganic fragment. In fact, even inorganic triphosphate can be employed as a substrate. Third, ANT(4') seems to be equipped with a duplicated basic catalyst that is able to promote drug inactivation through different reactive geometries. This particular combination of features explains the enzyme versatility and renders the design of non-inactivable derivatives a challenging task. PMID- 22298307 TI - Identification of candidate biomarkers for early detection of human lung squamous cell cancer by quantitative proteomics. AB - To discover novel biomarkers for early detection of human lung squamous cell cancer (LSCC) and explore possible mechanisms of LSCC carcinogenesis, iTRAQ tagging combined with two dimensional liquid chromatography tandem MS analysis was used to identify differentially expressed proteins in human bronchial epithelial carcinogenic process using laser capture microdissection-purified normal bronchial epithelium (NBE), squamous metaplasia (SM), atypical hyperplasia (AH), carcinoma in situ (CIS) and invasive LSCC. As a result, 102 differentially expressed proteins were identified, and three differential proteins (GSTP1, HSPB1 and CKB) showing progressively expressional changes in the carcinogenic process were selectively validated by Western blotting. Immunohistochemistry was performed to detect the expression of the three proteins in an independent set of paraffin-embedded archival specimens including various stage tissues of bronchial epithelial carcinogenesis, and their ability for early detection of LSCC was evaluated by receiver operating characteristic analysis. The results showed that the combination of the three proteins could perfectly discriminate NBE from preneoplastic lesions (SM, AH and CIS) from invasive LSCC, achieving a sensitivity of 96% and a specificity of 92% in discriminating NBE from preneoplatic lesions, a sensitivity of 100% and a specificity of 98% in discriminating NBE from invasive LSCC, and a sensitivity of 92% and a specificity of 91% in discriminating preneoplastic lesions from invasive LSCC, respectively. Furthermore, we knocked down GSTP1 in immortalized human bronchial epithelial cell line 16HBE cells, and then measured their susceptibility to carcinogen benzo(a)pyrene-induced cell transformation. The results showed that GSTP1 knockdown significantly increased the efficiency of benzo(a)pyrene-induced 16HBE cell transformation. The present data first time show that GSTP1, HSPB1 and CKB are novel potential biomarkers for early detection of LSCC, and GSTP1 down regulation is involved in human bronchial epithelial carcinogenesis. PMID- 22298310 TI - Disparities in access to care at high-volume institutions for uro-oncologic procedures. AB - BACKGROUND: Socioeconomic status represents an established barrier to health care access. Age, sex, and race may also play a role. The authors examined whether these affect the access to high-volume hospitals for uro-oncologic procedures in the United States. METHODS: Within the Nationwide Inpatient Sample (NIS), the authors focused on radical prostatectomy (RP), radical cystectomy, and nephrectomy (Nx) performed within the 5 most contemporary years (2003-2007). Logistic regression models were used to estimate the impact of the primary predictors on the likelihood of receiving care at a high-volume hospital. RESULTS: Between 2003 and 2007, 62,165 RP, 6557 radical cystectomy, and 28,062 Nx cases were recorded within the NIS. Patient age (P = .001), year of surgery (P = .001), Charlson Comorbidity Index (P <= .025), median Zip Code income (highest vs lowest quartile, P = .001), and insurance status (private vs Medicare, P = .008) were independent predictors of being treated at high-volume institutions. Moreover, black race was an independent predictor of decreased utilization of high-volume institutions for radical cystectomy (P = .012), and female sex was an independent predictor of decreased utilization of high-volume institutions for Nx (P = .016). CONCLUSIONS: On average, old, sick, poor, and Medicare patients were less likely to be treated at high-volume hospitals for uro-oncologic surgery. Similarly, black patients were less likely to have a radical cystectomy at a high volume hospital, and female patients were less likely to have an Nx at a high volume hospital. Selective referral of individuals who are less likely to receive care at such institutions may represent a health care priority intended to optimize outcomes across all population strata. PMID- 22298311 TI - Net costs of dementia in Sweden - an incidence based 10 year simulation study. AB - BACKGROUND: Aging of the population results in increasing number people suffering from dementia, and this will have a great impact on costs for the society. Because of the long duration of dementia disorders, it is difficult to collect empirical data for the whole survival period of incident cases. Therefore, modeling approaches are frequently used. The purpose of this study was to describe the costs of an incident dementia cohort with progression modeling. METHODS: Epidemiological data indicated that the incidence of dementia in Sweden was 24,000 people in 2005. Thus, incident cases were run in a Markov model for 10 cycles of 1 year each. Severity state specific costs were used and defined by Clinical Dementia Rating scale. RESULTS: Total cost for the cohort was 27.24 billion Swedish Krona (SEK). The mean cost per person and year was 269,558 SEK. Total cost for long-term institutional care was 21 billion SEK during the modeled period. CONCLUSION: Cost of long-term institutional care is the major cost driver, even in mild dementia. PMID- 22298312 TI - Analysis of cell adhesion during early stages of colon cancer based on an extended multi-valued logic approach. AB - Cell adhesion in the normal colon is typically associated with differentiated cells, whereas in cancerous colon it is associated with advanced tumors. For advanced tumors growing evidence supports the existence of stem-like cells that have originated from transdifferentiation. Because stem cells can also be transformed in their own niche, at the base of the Lieberkuhn's crypts, we conjectured that cell adhesion can also be critical in early tumorigenesis. To assess this hypothesis we built an annotated, multi-valued logic model addressing cell adhesion of normal and tumorigenic stem cells in the human colon. The model accounts for (i) events involving intercellular adhesion structures, (ii) interactions involving cytoskeleton-related structures, (iii) compartmental distribution of alpha/beta/gamma/delta-catenins, and (iv) variations in critical cell adhesion regulators (e.g., ILK, FAK, IQGAP, SNAIL, Caveolin). We developed a method that can deal with graded multiple inhibitions, something which is not possible with conventional logical approaches. The model comprises 315 species (including 26 genes), interconnected by 269 reactions. Simulations of the model covered six scenarios, which considered two types of colonic cells (stem vs. differentiated cells), under three conditions (normal, stressed and tumor). Each condition results from the combination of 92 inputs. We compared our multi-valued logic approach with the conventional Boolean approach for one specific example and validated the predictions against published data. Our analysis suggests that stem cells in their niche synthesize high levels of cytoplasmatic E-cadherin and CdhEP(Ser684,686,692), even under normal-mitogenic stimulus or tumorigenic conditions. Under these conditions, E-cadherin would be incorporated into the plasmatic membrane, but only as a non-adhesive CdhE_beta-catenin_IQGAP complex. Under stress conditions, however, this complex could be displaced, yielding adhesive CdhE_beta-catenin((cis/trans)) complexes. In the three scenarios tested with stem cells, desmosomes or tight junctions were not assembled. Other model predictions include expected levels of the nuclear complex beta-catenin_TCF4 and the anti-apoptotic protein Survivin for both normal and tumorigenic colonic stem cells. PMID- 22298313 TI - Changes in the tear film and ocular surface after cataract surgery. AB - PURPOSE: To evaluate changes in corneal sensitivity, tear film function, and ocular surface stability in patients after cataract surgery. METHODS: This hospital-based prospective randomized trial included 48 eyes from 30 patients who underwent phacoemulsification. Slit-lamp examination, Schirmer test 1 (ST1), and measurement of corneal sensitivity and tear film breakup time (BUT) were performed for all patients 1 day before and 1 day, 1 month, and 3 months after surgery. In addition, conjunctival impression cytology from the temporal region of the conjunctiva was simultaneously performed. RESULTS: Corneal sensitivity at the center and temporal incision sites had decreased significantly at 1 day postoperatively (P = .021, P < .001). However, the sensitivity had returned to almost the preoperative level 1 month postoperatively. The mean postoperative ST1 results were no different from preoperative values. On the other hand, BUT results had decreased significantly at 1 day postoperatively (P = .01) but had returned to almost the preoperative level 1 month postoperatively. Mean goblet cell density (GCD) had decreased significantly at 1 day, 1 month, and 3 months postoperatively (P < .001). In addition, decrease in GCD and cataract operative time were highly correlated (r2 = 0.65). CONCLUSIONS: The decrease in GCD, which was correlated with operative time, had not recovered at 3 months after cataract surgery. Therefore, microscopic ocular surface damage during cataract surgery seems to be one of the pathogenic factors that cause ocular discomfort and dry eye syndrome after cataract surgery. PMID- 22298314 TI - The photochemistry of [Fe(III)N3(cyclam-ac)]PF6 at 266 nm. AB - The photochemistry of iron azido complexes is quite challenging and poorly understood. For example, the photochemical decomposition of [Fe(III)N(3)(cyclam ac)]PF(6) ([1]PF(6)), where cyclam-ac represents the 1,4,8,11 tetraazacyclotetradecane-1-acetate ligand, has been shown to be wavelength dependent, leading either to the rare high-valent iron(V) nitrido complex [Fe(V)N(cyclam-ac)]PF(6) ([3]PF(6)) after cleavage of the azide N(alpha)-N(beta) bond, or to a photoreduced Fe(II) species after Fe-N(azide) bond homolysis. The mechanistic details of this intriguing reactivity have never been studied in detail. Here, the photochemistry of 1 in acetonitrile solution at room temperature has been investigated using step-scan and rapid-scan time-resolved Fourier transform infrared (FTIR) spectroscopy following a 266 nm, 10 ns pulsed laser excitation. Using carbon monoxide as a quencher for the primary iron containing photochemical product, it is shown that 266 nm excitation of 1 results exclusively in the cleavage of the Fe-N(azide) bond, as was suspected from earlier steady-state irradiation studies. In argon-purged solutions of [1]PF(6), the solvent-stabilized complex cation [Fe(II)(CH(3)CN)(cyclam-ac)](+) (2red) together with the azide radical (N(3)(.)) is formed with a relative yield of 80%, as evidenced by the appearance of their characteristic vibrational resonances. Strikingly, step-scan experiments with a higher time resolution reveal the formation of azide anions (N(3)(-)) during the first 500 ns after photolysis, with a yield of 20%. These azide ions can subsequently react thermally with 2red to form [Fe(II)N(3)(cyclam-ac)] (1red) as a secondary product of the photochemical decomposition of 1. Molecular oxygen was further used to quench 1red and 2red to form what seems to be the elusive complex [Fe(O(2))(cyclam ac)](+) (6). PMID- 22298315 TI - Influences of the insertion method in glass ionomer cement porosity. AB - The aim of this study was to evaluate the presence of porosities inside the glass ionomer cement (GIC) after different techniques of material insertion. MATERIAL AND METHOD: Specimens were prepared with high-viscosity GIC Ketac Molar Easymix and divided into three groups according to the insertion method: spatula (PI), Centrix injector (CI), and low-cost syringe (LCS). The specimens were fractured and observed with scanning electronic microscopy to quantitatively evaluate porosity inside the material using Image J Software. RESULTS: Statistical analysis, ANOVA application, and Tukey test to significance level of 5%, revealed that there was no statistical difference between the groups. CONCLUSION: Although the use of LCS has not decreased the porosity of the material, this insertion method is easy, accessible, and low cost, which makes it a viable alternative of use in the ART technique and in others bucal health programs. PMID- 22298316 TI - The surface chemistry of water on Fe(100): a density functional theory study. AB - The formation of water by hydrogenation of atomic oxygen is studied using density functional theory. Atomic oxygen preferentially adsorbs at the four-fold hollow site, the hydroxyl group prefers the bridge site in a tilted configuration, and water is most stable when adsorbed at the top site with the two O-H bonds parallel to the Fe surface. Water formation by the hydrogenation of oxygen is a highly activated process on the Fe(100) surface, with similar activation energies, in the order of 1.1 eV, for the first and second hydrogen additions. A more favourable route for the addition of the second hydrogen atom involves the disproportionation of hydroxyl groups to form water and adsorbed oxygen. Dissociation of the OH is also likely since the activation energy is similar to that for disproportionation of 0.65 eV. Furthermore, the results show that the dissociation of water on Fe(100) is a non-activated process: 0.16 eV for the zero coverage limit and 0.03 eV when surface oxygen is present. Herein, adsorption energies, structures and vibrational frequencies are presented for several adsorption states at 0.25 ML coverage, as well as the potential energy surface for water formation on Fe(100). PMID- 22298319 TI - Exploring biological electron transfer pathway dynamics with the Pathways plugin for VMD. AB - We describe the new Pathways plugin for the molecular visualization program visual molecular dynamics. The plugin identifies and visualizes tunneling pathways and pathway families in biomolecules, and calculates relative electronic couplings. The plugin includes unique features to estimate the importance of individual atoms for mediating the coupling, to analyze the coupling sensitivity to thermal motion, and to visualize pathway fluctuations. The Pathways plugin is open source software distributed under the terms of the GNU's Not Unix (GNU) public license. PMID- 22298320 TI - Observation of the highest coordination number in planar species: decacoordinated Ta(c)B10(-) and Nb(c)B10(-) anions. PMID- 22298321 TI - Overexpression of hTERT extends replicative capacity of human nucleus pulposus cells, and protects against serum starvation-induced apoptosis and cell cycle arrest. AB - The nucleus pulposus (NP) cells are chondrocyte-like cells that are required for the resistance of compressive loads through the synthesis of collagen fibrils and proteoglycan aggrecans, and the generation of a hydrostatic swelling pressure, and thus play an important role in the intervertebral disc. Here, we report the production and characterization of an immortalized human NP cell line from normal NP cells using stable transfection of recombinant human telomerase reverse transcriptase (hTERT) gene. The hTERT-transfected NP cells exhibited morphological characteristics typical of native cells. When compared with the first generation of normal NP cells, the hTERT-transfected NP cells grew faster and had an increased level of IGF-1 and TGF-beta gene expression. They were successfully passaged over 20 generations without significant change in the levels of type II collagen and proteoglycan aggrecan expression. In addition, they showed resistance to serum starvation-induced apoptosis, G1 cell cycle arrest, and gene expression of p53, CCNE1, Fas, and Caspase 3. Moreover, histology revealed that no tumorigenicity of NP cells over expressing hTERT was observed after they were implanted in nude mice. Taken together, an immortalized human NP cell line was established, which has an extended lifespan, retains phenotypic features similar to primary parent NP cells, and should provide a suitable model for studying the biology of NP cells. PMID- 22298322 TI - Designer ionic liquid crystals based on congruently shaped guanidinium sulfonates. AB - Ionic liquid crystals are mesogenic compounds that consist of cations and anions, usually rod-like cations and spherical anions. Herein we report a new method for the synthesis of ionic liquid crystals by using cations and anions of the same molecular shape with oppositely charged head groups. Thus, 4 alkoxyphenylpentamethylguanidinium 4-alkoxyphenylsulfonate ion pairs have been synthesised. 4-Alkoxyphenylpentamethylguanidinium iodides were also prepared to determine the influence of congruently shaped anions, in comparison with their spherical counterparts, on mesophase behaviour, which was investigated by differential scanning calorimetry (DSC), polarising optical microscopy (POM) and X-ray diffraction (XRD). All the liquid crystalline salts exhibit smectic A mesophases with strongly interdigitated bilayer structures. The guanidinium sulfonate ion pairs show mesomorphic properties from shorter alkyl chain lengths (>=C(9)) and lower melting points (~10 K), whereas the corresponding guanidinium iodides are liquid crystalline for longer alkyl chain lengths (>=C(14)). For chains with >=C(18), however, the mesophase range decreases for the sulfonate ion pairs, but not for the iodide salts. PMID- 22298323 TI - Erythroblastosis in the peritoneal fluid of a newborn. PMID- 22298324 TI - A convenient and practical synthesis of anisoles and deuterated anisoles by palladium-catalyzed coupling reactions of aryl bromides and chlorides. PMID- 22298325 TI - Transparent luminescent bulk nanocomposites of polysiloxane embedded with CdS nanocrystallines by a direct dispersion process. AB - Transparent luminescent bulk nanocomposites of polysiloxane (PSO) embedded with semiconductor nanocrystals (NCs) have been fabricated by the direct dispersion of CdS NCs in alkyl-(poly)siloxane (APS) followed by co-polymerization. The non polar characteristics of the APS precursor are compatible with the CdS NC surface (oleylamine), which allows the direct dispersion of the CdS NCs without the need of any surfactant exchange. Chemical crosslinking of the NC-APS dispersion via hydrosilylation between Si-H and the vinyl group in APS immobilizes the CdS NCs in the polysiloxane network. Net-shaped three-dimensional bulk transparent polysiloxane/CdS NC composites were obtained by liquid casting of the NC precursor dispersion and chemical crosslinking. The PSO/CdS NC composites show visible luminescence under ultraviolet excitation and the luminescent color is tunable from blue to red by controlling the NC concentration in the composite. Photoluminescence spectral analyses reveal the origin of the luminescence as being from the defect emission of the CdS NCs (550-900 nm) and an emission from the PSO matrix (380-550 nm). The luminescent spectra covered a wide range from the ultraviolet to the near-infrared region. The luminescence of the PSO/CdS NC nanocomposites was stable without any apparent degradation after exposure to air for a long time. This simple direct dispersion process is feasible for the fabrication of luminescent nanocomposites with useful optical properties for potential applications in optics and photoelectron devices. PMID- 22298326 TI - Gross and microscopic observations on the lingual structure of the Franciscana (Pontoporia blainvillei--Gervais and d'Orbigny, 1844). AB - In most anatomical studies developed with mammals, the tongue is described as highly differentiated among different species. However, studies on the tongue of aquatic mammals are still limited as compared to those on terrestrial mammals. The aim of this study was to describe the tongue morphology of the Franciscana dolphin (Pontoporia blainvillei) using macroscopic observations, light, and scanning electron microscopy. Microscopically, the dorsal surface was covered by a keratinized stratified epithelium. Salivary gland acini were found on the middle and caudal third of the tongue. The dorsal surface was totally covered by filiform papillae with a connective tissue core and a connective tissue structure round in shape in the middle and caudal regions. PMID- 22298327 TI - Spectroscopic properties of gold nanoparticles at the single-particle level in biological environments. AB - Labeling cells and tissues with fluorescent probes, such as organic dyes and quantum dots (Qdots) is a widespread and successful technique for studying molecular dynamics both in vitro and in vivo. However, those probes usually suffer from undesirable photophysical/photochemical processes, such as blinking and photobleaching, limiting their utilization. The main challenges in fluorescent probe design are to improve their absorption/emission properties, and to provide higher stability against photobleaching. In the last few years, metallic nanoparticles (NPs) of various sizes, shapes, and compositions have been used as a new alternative for cellular microscopy. This is in part because-unlike common organic dyes and Qdots-metallic NPs do not bleach or blink upon continuous illumination, are extremely stable, very bright, and their luminescence spans over the visible spectrum. These characteristics make them attractive contrast agents for cell imaging both in vitro and in vivo. For these reasons, the emission of metallic NPs in bulk solutions has already been extensively characterized. In contrast with bulk experiments, where billions of molecules are measured simultaneously, single-particle techniques allow the observation of characteristics and dynamical processes otherwise hidden in the measured average. A full understanding of the photophysical properties of the NPs is critical when they are used for single-molecule applications. Photophysical processes can be a source of artifacts if they are not interpreted accordingly, and thus a careful characterization of these labels at the single-particle level became crucial for the correct interpretation of the experimental results. Herein, we study some of their unique optical properties at the single-particle level and show examples that illustrate their intrinsic heterogeneity when used in biological environments. PMID- 22298328 TI - Semantic memory and language dysfunction in early Alzheimer's disease: a review. AB - BACKGROUND: Language impairment in Alzheimer's disease occurs early, and language function deteriorates with progression of the illness to cause significant disability. This review focuses on language dysfunction in Alzheimer's disease and the contribution of semantic memory impairment. METHODS: Electronic publication databases were searched for literature relevant to the review. Additionally, individual references were examined to elicit further studies not found by online search. RESULTS: Language impairment in Alzheimer's disease initially affects verbal fluency and naming before breakdown in other facets. Naming and fluency require integrity of semantic concepts, and dysfunction may be a marker of primary semantic memory impairment rather than overall cognitive decline. Research suggests the presence of semantic loss several years prior to diagnosis. Imaging studies indicate an altered connectivity state with respect to language networks, and this is associated with potential semantic failure. This state may also be present in individuals with established risk factors for Alzheimer's disease. Compensatory recruitment of alternative cortical areas to supplement language function appears to occur and may be a target for future intervention. CONCLUSIONS: Identifying and classifying the nature and degree of language impairment more closely could aid in developing targeted therapies. Treatments already established in other aphasic states, such as post-stroke, may be especially relevant. The nature of these and the protective nature of cognitive reserve are potential therapeutic avenues. PMID- 22298329 TI - Development of a finite element model for blast brain injury and the effects of CSF cavitation. AB - Blast-related traumatic brain injury is the most prevalent injury for combat personnel seen in the current conflicts in Iraq and Afghanistan, yet as a research community,we still do not fully understand the detailed etiology and pathology of this injury. Finite element (FE) modeling is well suited for studying the mechanical response of the head and brain to blast loading. This paper details the development of a FE head and brain model for blast simulation by examining both the dilatational and deviatoric response of the brain as potential injury mechanisms. The levels of blast exposure simulated ranged from 50 to 1000 kPa peak incident overpressure and 1-8 ms in positive-phase duration, and were comparable to real-world blast events. The frontal portion of the brain had the highest pressures corresponding to the location of initial impact, and peak pressure attenuated by 40-60% as the wave propagated from the frontal to the occipital lobe. Predicted brain pressures were primarily dependent on the peak overpressure of the impinging blast wave, and the highest predicted brain pressures were 30%less than the reflected pressure at the surface of blast impact. Predicted shear strain was highest at the interface between the brain and the CSF. Strain magnitude was largely dependent on the impulse of the blast, and primarily caused by the radial coupling between the brain and deforming skull.The largest predicted strains were generally less than 10%,and occurred after the shock wave passed through the head.For blasts with high impulses, CSF cavitation had a large role in increasing strain levels in the cerebral cortex and periventricular tissues by decoupling the brain from the skull. Relating the results of this study with recent experimental blast testing suggest that a rate dependent strain-based tissue injury mechanism is the source primary blast TBI. PMID- 22298330 TI - Na2.8Cu5Sn5.6: A crystalline alloy featuring intermetalloid (1)(infinity){Sn(0.6@Cu(5)@Sn(5)} double-walled nanorods with pseudo-five-fold symmetry. AB - Not quasi-crystalline: approximate five-fold symmetry appears in bronze-type Cu Sn rods that are separated by Na atoms in Na(2.8)Cu(5)Sn(5.6). The rods are compared to the [Sn@Cu(12)@Sn(20)](12-) cluster in the recently characterized A(12)Cu(12)Sn(21) phases (A=Na-Cs), and a saltlike description in analogy to Zintl phases of p-block metals is introduced for these new polar intermetallic phases with a high d-block metal content. PMID- 22298331 TI - Clinical significance of circulating interleukin-23 as a prognostic factor in breast cancer patients. AB - Little is known about specific IL-23 alterations associated with breast cancer and the data available are still controversial. Therefore, the evaluation of changes in serum IL-23 levels may add further information on the role of this cytokine in breast cancer patients. The aim of this study was to evaluate prospectively the prognostic importance of circulating IL-23 in patients with untreated breast cancer, respect to healthy controls, and the association with clinico-pathological variables. The study involved 50 women diagnosed with stages I-IV breast cancer and 38 healthy controls. Of the 50 breast cancer patients, 37 women were recruited prior to their initial adjuvant chemotherapy and 13 prior to receive first line chemotherapy for metastatic disease. Adjuvant chemotherapy patients were at least in their 4th week post-surgery. IL-23 serum concentrations were measured by a quantitative enzyme immunoassay technique. We found a statistically significant higher systemic cytokine value in women with cancer in comparison with the control group (14.52+/-11.39 pg/ml vs. 6.35+/-4.63 pg/ml, P<0.0001). Patients with shorter overall survival presented higher IL-23 values, suggesting a negative prognostic correlation. There was no significant differences in IL-23 levels among patients according to the biomolecular characteristics, the different subtypes and the presence of metastatic disease. This work investigated, for the first time, the role of IL-23 in breast cancer patients showing a significant increase respect the control group. However, further validations are needed in larger studies to better investigate the implications of IL-23 increase in these patients. PMID- 22298332 TI - Influence of the solvent representation on vibrational entropy calculations: generalized born versus distance-dependent dielectric model. AB - The harmonic model is the most popular approximation for estimating the "configurational" entropy of a solute in molecular mechanics/Poisson-Boltzmann solvent accessible surface area (MM/PBSA)-type binding free energy calculations. Here, we investigate the influence of the solvent representation in the harmonic model by comparing estimates of changes in the vibrational entropies for 30 trypsin/ligand complexes on ligand binding. Second derivatives of Amber generalized Born (GB) solvation models are available in the nucleic acid builder code. They allow one to use these models for the calculation of vibrational entropies instead of using a simpler solvation model based on a distance dependent dielectric (DDD) constant. Estimates of changes in the vibrational entropies obtained with a DDD model are systematically and significantly larger, by on average, 6 kcal mol(-1) (at T = 300 K), than estimates obtained with a GB model and so are more favorable for complex formation. The difference becomes larger the more the vibrational entropy contribution disfavors complex formation, that is, the larger the ligand is (for the complexes considered here). A structural decomposition of the estimates into per-residue contributions reveals polar interactions between the ligand and the surrounding protein, in particular involving charged nitrogens, as a main source of the differences. Snapshots minimized with the DDD model showed a structural deviation from snapshots minimized in explicit water that is larger by, on average, 0.5 A RMSD compared to snapshots that were minimized with GB(HCT) . As experimental vibrational entropies of biomacromolecules are elusive, there is no direct way to establish a solvent model's superiority. Thus, we can only recommend using the GB harmonic model for vibrational entropy calculations based on the reasoning that smaller structural deviations should point to the implicit solvent model that closer approximates the energy landscape of the solute in explicit solvent. PMID- 22298333 TI - Organic dyes containing pyrenylamine-based cascade donor systems with different aromatic pi linkers for dye-sensitized solar cells: optical, electrochemical, and device characteristics. AB - New organic dyes containing pyrenylamine donors in a cascade arrangement and cyanoacrylic acid acceptors have been synthesized and characterized by optical, electrochemical, and theoretical studies. The dyes inherit a D-pi(1)-D-pi(2)-A (D=donor, A=acceptor) molecular architecture where the pi linkers pi(1) are changed from phenyl to biphenyl and fluorene, whereas the pi linker pi(2) that connects the donor fragment with the acceptor is a phenyl unit. The conjugation pathway linking the two donor segments has been found to play a major role in the optical and electrochemical properties. Shorter pi linkers such as phenyl groups facilitate the donor-acceptor interaction while the nonplanar biphenyl spacer decreases the electronic communication between the donors and enhances the oxidation propensity of the corresponding dye. All the dyes display an intense longer wavelength electronic transition,which is attributable to the amine-to cyanoacrylic acid charge transfer. The extinction coefficient of this peak grows dramatically on increasing the conjugation pathway length between the two donor segments. The dyes were used as sensitizers in nanocrystalline TiO(2)-based dye sensitized solar cells (DSSCs) and the cascade donor system contributed to the enhancement in the device efficiency due to favorable absorption and redox properties. PMID- 22298334 TI - A disulfide bridge allows for site-selective binding in liver bile acid binding protein thereby stabilising the orientation of key amino acid side chains. AB - The presence of a disulfide bridge in liver bile acid binding protein (L-BABP/S S) allows for site-selective binding of two bile acids, glycochenodeoxycholic (GCDA) and glycocholic acid (GCA), differing only in the presence of a hydroxyl group. The protein form devoid of the disulfide bridge (L-BABP) binds both bile salts without discriminating ability. We investigate the determinants of the molecular recognition process in the formation of the heterotypic L-BABP/S-S complex with GCDA [corrected] and GCA [corrected] located in the superficial and inner protein sites, respectively. The comparison of the NMR spectroscopy structure of heterotypic holo L-BABP/S-S, the first reported for this protein family, with that of the homotypic L-BABP complex demonstrates that the introduction of a S-S link between adjacent strands changes the conformation of three key residues, which function as hot-spot mediators of molecular discrimination. The favoured chi(1) rotameric states (t, g(+) and g(-) for E99, Q100 and E109 residues, respectively) allow the onset of an extended intramolecular hydrogen-bond network and the consequent stabilisation of the side chain orientation of a buried histidine, which is capable of anchoring a specific ligand. PMID- 22298335 TI - Aspiration cytology of mesenchymal hamartoma of the liver: report of a case and review of literature. PMID- 22298336 TI - Direct regiospecific and highly enantioselective intermolecular alpha-allylic alkylation of aldehydes by a combination of transition-metal and chiral amine catalysts. AB - The first direct intermolecular regiospecific and highly enantioselective alpha allylic alkylation of linear aldehydes by a combination of achiral bench-stable Pd(0) complexes and simple chiral amines as co-catalysts is disclosed. The co catalytic asymmetric chemoselective and regiospecific alpha-allylic alkylation reaction is linked in tandem with in situ reduction to give the corresponding 2 alkyl alcohols with high enantiomeric ratios (up to 98:2 e.r.; e.r.=enantiomeric ratio). It is also an expeditious entry to valuable 2-alkyl substituted hemiacetals, 2-alkyl-butane-1,4-diols, and amines. The concise co-catalytic asymmetric total syntheses of biologically active natural products (e.g., Arundic acid) are disclosed. PMID- 22298337 TI - Photobleaching and blinking of TAMRA induced by Mn(2+). AB - Blinking and bleaching: Coordination of Mn(2+) to DNA induces intersystem crossing, causing fluctuations in the fluorescence intensity and accelerated photobleaching. PMID- 22298338 TI - Expression of TRPV4 in the zebrafish retina during development. AB - The transient receptor potential (TRP) channels are involved in sensing mechanical/physical stimuli such as temperature, light, pressure, as well as chemical stimuli. Some TRP channels are present in the vertebrate retina, and the occurrence of the multifunctional channel TRP vanilloid 4 (TRPV4) has been reported in adult zebrafish. Here, we investigate the expression and distribution of TRPV4 in the retina of zebrafish during development using polymerase chain reaction (PCR), Western blot, and immunohistochemistry from 3 days post fertilization (dpf) until 100 dpf. TRPV4 was detected at the mRNA and protein levels in the eye of zebrafish at all ages sampled. Immunohistochemistry revealed the presence of TRPV4 in a population of the retinal cells identified as amacrine cells on the basis of their morphology and localization within the retina, as well as the co-localization of TRPV4 with calretinin. TRPV4 was first (3 dpf) found in the soma of cells localized in the inner nuclear and ganglion cell layers, and thereafter (10 dpf) also in the inner plexiform layer. The adult pattern of TRPV4 expression was achieved by 40 dpf the expression being restricted to the soma of some cells in the inner nuclear layer and ganglion cell layers. These data demonstrate the occurrence and developmental changes in the expression and localization of TRPV4 in the retina of zebrafish, and suggest a role of TRPV4 in the visual processing. PMID- 22298339 TI - Sexual risk taking in relation to sexual identification, age, and education in a diverse sample of African American men who have sex with men (MSM) in New York City. AB - HIV disproportionately affects African American men who have sex with men (MSM) in the United States. To inform this epidemiological pattern, we examined cross sectional sexual behavior data in 509 African American MSM. Bivariate logistic regression analyses were conducted to examine the extent to which age, education,and sexual identity explain the likelihood of engaging in sex with a partner of a specific gender and the likelihood of engaging in unprotected sexual behaviors based on partner gender. Across all partner gender types,unprotected sexual behaviors were more likely to be reported by men with lower education. Younger, non-gay identified men were more likely to engage in unprotected sexual behaviors with transgender partners, while older, non-gay identified men were more likely to engage in unprotected sexual behaviors with women. African American MSM do not represent a monolithic group in their sexual behaviors, highlighting the need to target HIV prevention efforts to different subsets of African American MSM communities as appropriate. PMID- 22298340 TI - A randomized controlled trial to evaluate the relative efficacy of enhanced versus standard voluntary counseling and testing on promoting condom use among men who have sex with men in China. AB - The randomized controlled trial investigated the relative efficacy of an enhanced (EVCT) versus standard (SVCT) voluntary counseling and testing in reducing unprotected anal intercourse (UAI) among men who have sex with men (MSM) in China. 295 participants who recruited by respondent driven sampling methods were randomly allocated to the two arms. In addition to the SVCT, the EVCT group watched a theory-based video narrated by a HIV positive MSM, received enhanced counseling and a reminder gift. As compared to the SVCT group, the EVCT group reported lower prevalence of UAI with any male sex partners (48.4% versus 66.7%, RR = 0.7, ARR = -18.3%, p = 0.010) and with regular male sex partners (52.2% versus 68.9%, RR = 0.8, ARR = -16.7%, p = 0.043) at Month 6, whilst baseline between-group differences were statistically non-significant. Between-group differences in HIV/syphilis incidence were statistically non-significant. Translational research should be conducted to integrate non-intensive enhancements such as the EVCT into regular testing services. PMID- 22298341 TI - Occurrence of new sexually transmitted diseases in males after HIV diagnosis. AB - Risk reduction following an HIV diagnosis is important for controlling the epidemic. The objective of this retrospective cohort study of 6,965 HIV-positive males was to evaluate the joint risk of new reportable STDs in males after HIV diagnosis by race/ethnicity and risk behavior. This investigation linked HIV case reports with STD surveillance, clinical care and laboratory datasets to determine new STD acquisition in HIV positive individuals.Compared to White MSM with high care engagement,Black MSM had a significantly higher rate of new reportable STDs for the full time period after HIV diagnosis, B1 year after diagnosis, and[1 year after diagnosis. High HIV care engagement was not as protective against new STD acquisition for Black MSM as it was for White MSM and reasons for this health disparity should be explored. PMID- 22298342 TI - In situ anionic shielding for regioselective metalation: directed peri and iterative metalation routes to polyfunctionalized 7-azaindoles. AB - Strolling the ring: a general regioselective directed peri(C4)-metalation route to 1 through an in situ N-anionic protection of C2 is reported. The azaindoles may be elaborated by directed ortho metalation (DoM) and Suzuki coupling to more complex heterocyclic systems. An iterative ring-walk DoM sequence furnishes the exhaustively substituted 2. DMG=directed metalation group, TMEDA=N,N,N',N' tetramethylethylenediamine, TMS=trimethylsilyl. PMID- 22298343 TI - Deep sequencing reveals predominant expression of miR-21 amongst the small non coding RNAs in retinal microvascular endothelial cells. AB - The retinal vascular endothelium is essential for angiogenesis and is involved in maintaining barrier selectivity and vascular tone. The aim of this study was to identify and quantify microRNAs and other small regulatory non-coding RNAs (ncRNAs) which may regulate these crucial functions. Primary bovine retinal microvascular endothelial cells (RMECs) provide a well-characterized in vitro system for studying angiogenesis. RNA extracted from RMECs was used to prepare a small RNA library for deep sequencing (Illumina Genome Analyzer). A total of 6.8 million reads were mapped to 250 known microRNAs in miRBase (release 16). In many cases, the most frequent isomiR differed from the sequence reported in miRBase. In addition, five novel microRNAs, 13 novel bovine orthologs of known human microRNAs and multiple new members of the miR-2284/2285 family were detected. Several ~30 nucleotide sno-miRNAs were identified, with the most highly expressed being derived from snoRNA U78. Highly expressed microRNAs previously associated with endothelial cells included miR-126 and miR-378, but the most highly expressed was miR-21, comprising more than one-third of all mapped reads. Inhibition of miR-21 with an LNA inhibitor significantly reduced proliferation, migration, and tube-forming capacity of RMECs. The independence from prior sequence knowledge provided by deep sequencing facilitates analysis of novel microRNAs and other small RNAs. This approach also enables quantitative evaluation of microRNA expression, which has highlighted the predominance of a small number of microRNAs in RMECs. Knockdown of miR-21 suggests a role for this microRNA in regulation of angiogenesis in the retinal microvasculature. PMID- 22298344 TI - Synthesis and spectroscopic properties of phthalocyanine-[60]fullerene conjugates connected directly by means of a four-membered ring. AB - New covalently C(60)-conjugated phthalocyanine (Pc) analogues in which the Pc and C(60) components are connected by means of a four-membered ring have been synthesized by taking advantage of a [2+2] cycloaddition reaction of C(60) with benzyne units generated from either a phthalocyanine derivative (8) or its precursor (1). The reaction of 1 with PhI(OAc)(2) and trifluoromethanesulfonic acid (TfOH) followed by the [2+2] cycloaddition of C(60) in the presence of tetra n-butylammonium fluoride (TBAF) yielded the C(60)-substituted Pc precursor (3). Mixed condensation of 3 and 4,5-dibutylsulfonylphthalonitrile (4) in a thermally promoted template reaction using a nickel salt successfully gave the Pc-C(60) conjugate (5). Results of mass spectrometry and (1)H and (13)C NMR spectroscopy clearly indicate the formation of the anticipated Pc-C(60) conjugate. Direct coupling of C(60) with the Pc analogue that contained eight peripheral trimethylsilyl (TMS) groups (8) also proceeded successfully, such that mono and bis C(60)-adducts were detected by their mass, although the isolation of each derivative was difficult. The absorption and magnetic circular dichroism (MCD) spectra of 5 and the reference compound (7) differ from each other in the Q-band region, thereby suggesting that the presence of the C(60) moiety affects the electronic structure of the conjugate. The reduction and oxidation potentials of 5 and 7 obtained by cyclic voltammetry are comparative, except for the C(60) centered reduction couple at -1.53 V versus Fc(+)/Fc in o-dichlorobenzene (o DCB). A one-electron reduction of 5 and 7 in tetrahydrofuran (THF) by using the sodium mirror technique results in the loss of band intensity in the Q-band region, whereas the characteristic marker bands for Pc-ring-centered reduction appear at around 430, 600, and 900 nm for both compounds. The final spectral shapes of 5 and 7 upon the reduction resemble each other, thus indicating that no significant molecular orbital (MO) interactions between the C(60) and Pc units are present for the reduced species of 5. In contrast, the oxidized species of 5 and 7 generated by the addition of NOBF(4) in CH(2)Cl(2) show significantly different absorption spectra from each other. Whereas the broad bands at approximately 400-550 nm of 7(+) are indicative of the cationic pi-radical species of metallo-Pcs and can be assigned to a transition from a low-lying MO to the half-filled MO, no corresponding bands were observed for 5(+). These spectral characteristics have been tentatively assigned to the delocalized occupied frontier MOs for 5(+). The experimental results are broadly supported by DFT calculations. PMID- 22298345 TI - Electric field and current density distribution in an anatomical head model during transcranial direct current stimulation for tinnitus treatment. AB - Tinnitus is considered an auditory phantom percept. Recently, transcranial direct current stimulation (tDCS) has been proposed as a new approach for tinnitus treatment including, as potential targets of interest, either the temporal and temporoparietal cortex or prefrontal areas. This study investigates and compares the spatial distribution of the magnitude of the electric field and the current density in the brain tissues during tDCS of different brain targets. A numerical method was applied on a realistic human head model to calculate these field distributions in different brain structures, such as the cortex, white matter, cerebellum, hippocampus, medulla oblongata, pons, midbrain, thalamus, and hypothalamus. Moreover, the same distributions were evaluated along the auditory pathways. Results of this study show that tDCS of the left temporoparietal cortex resulted in a widespread diffuse distribution of the magnitude of the electric fields (and also of the current density) on an area of the cortex larger than the target brain region. On the contrary, tDCS of the dorsolateral prefrontal cortex resulted in a stimulation mainly concentrated on the target itself. Differences in the magnitude distribution were also found on the structures along the auditory pathways. A sensitivity analysis was also performed, varying the electrode position and the human head models. Accurate estimation of the field distribution during tDCS in different regions of the head could be valuable to better determine and predict efficacy of tDCS for tinnitus suppression. PMID- 22298346 TI - Mononucleotide-modified metal nanoparticles: an efficient colorimetric probe for selective and sensitive detection of aluminum(III) on living cellular surfaces. PMID- 22298347 TI - Good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) in adults in the UK: a consensus statement. AB - These good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) are an update to a previous consensus statement on OPAT in the UK published in 1998. They are based on previous national and international guidelines, but have been further developed through an extensive consultation process, and are underpinned by evidence from published literature on OPAT. They provide pragmatic guidance on the development and delivery of OPAT services, looking at all aspects of service design, care delivery, outcome monitoring and quality assurance, with the aim of ensuring that OPAT services provide high quality, low-risk care, whatever the healthcare setting. They will provide a useful resource for teams developing new services, as well as a practical set of quality indicators for existing services. PMID- 22298349 TI - Blood and CSF monitoring of cefepime-induced neurotoxicity: nine case reports. PMID- 22298348 TI - Viral tropism by geno2pheno as a tool for predicting CD4 decrease in HIV-1 infected naive patients with high CD4 counts. AB - OBJECTIVES: To investigate the value of tropism (determined by genotypic testing) to predict CD4 depletion in HIV-infected antiretroviral-naive patients with high CD4 counts. METHODS: Viral tropism was determined by geno2pheno (false positive rate = 10%) in 223 HIV-infected subjects naive to antiretrovirals with CD4 count >=350 cells/MUL and HIV-RNA >500 copies/mL enrolled in the ICONA Foundation Study for whom a stored plasma sample (baseline) was retrospectively tested. We monitored CD4 cell count and identified predictors of decline before antiretroviral therapy initiation, applying a mixed linear model with covariates (age, gender, tropism, HIV risk factor, calendar year of HIV infection, months from HIV diagnosis to baseline, hepatitis C virus status, CD4 and HIV-RNA at sample collection and duration of follow-up). RESULTS: Two hundred and twenty three subjects met the eligibility criteria; 137 (61%) were male and the median age was 35 (31-40) years. Median follow-up was 16.4 (3.2-37.2) months. Median CD4 decrease during follow-up was -157 (-278 to -13) cells/MUL. At baseline, 192 (86%) subjects were defined as harbouring R5 virus and 31 (14%) non-R5. Median CD4 count was 571 (458-729) cells/MUL and median HIV-RNA was 4.08 (3.57-4.55) log(10) copies/mL. At multivariable analysis, a greater mean CD4 decrease was associated with non-R5 viral tropism (-159.9 +/- 12.22, P = 0.0002) at baseline. Other significant covariates were female gender, older age, intravenous drug use, longer duration of follow-up, and higher CD4 cell count and higher HIV-RNA at sample collection. CONCLUSIONS: In patients with CD4 counts >=350 cells/MUL, non R5 viral tropism by geno2pheno is predictive of CD4 decrease independent of their viral set point and CD4 counts. PMID- 22298350 TI - Response to article: "Lang TU et al. molluscum contagiosum of the cervix.". PMID- 22298351 TI - Synthesis of optically active oxazoline derivatives via catalytic asymmetric desymmetrization of 1,3-diols. PMID- 22298352 TI - Effect of disinfectant solutions on gutta-percha and resilon cones. AB - The aim of this study was to evaluate the effects of the 5.25% sodium hypochlorite (NaOCl), 2% chlorhexidine (CHX), and MTAD solutions on the surface of gutta-percha and Resilon cones by using atomic force microscopy (AFM). Accessory cones were washed and dried. The cones were randomly divided into six groups: gutta-percha immersed in NaOCl, CHX, and MTAD, and Resilon immersed in NaOCl, CHX, and MTAD. AFM images of the same area were made in different periods of time. JPKTM Image Processing Software was used to evaluate the images. The parameters used to evaluate the changes were RMS and line profiles. No statistically significant change was observed in the RMS values. The line profiles detected changes only for gutta-percha surfaces after immersion in NaOCl and MTAD solutions. In conclusion, 5.25% NaOCl and MTAD are associated with local changes in surface roughness of gutta-percha cones. No change was observed when 2% CHX was used. The use of all tested solutions did not produce any changes on Resilon surface. PMID- 22298353 TI - Structure-property relationships in ionic liquids: a study of the anion dependence in vaporization enthalpies of imidazolium-based ionic liquids. AB - Vaporization enthalpies for a series of ionic liquids (ILs) with the common cation 1-ethyl-3-methylimidazolium [C(2)mim] and different counter anions are determined using a quartz crystal microbalance method. Dependences of vaporization enthalpies on physicochemical parameters specific for cation and anion interactions are revealed. A linear relation between enthalpies of vaporization and the intermolecular vibrational frequencies is observed and suggested for calculation of unknown ILs. A simple group-contribution method is developed for prediction of vaporization enthalpies of alkyl imidazolium-based ILs. PMID- 22298354 TI - Dynamic mapping of CN rotation following photoexcitation of ICN-. AB - In a spin: the dynamics of photoexcited ICN(-) (Ar)(0-5) are presented. Photodetachment produces quasi-thermal electron emission that leaves ICN with up to 2.85 eV of internal energy. Photodissociation at 2.5 eV leads to one-atom caging and highly solvated anion products. Calculations indicate efficient energy transfer into CN rotation upon excitation to the (2)Pi(1/2) excited state. CN rotation is vital to explain the unique dynamics observed. PMID- 22298355 TI - Determination of genetic diversity of Vitis vinifera cv. Kabarcik populations from the Coruh Valley using SSR markers. AB - Northeastern Turkey is recognized as one of the most important germplasm centers for the grape in the world. In the present study, simple sequence repeat markers were used to investigate the genetic diversity between four Vitis vinifera cv. Kabarcik populations sampled from the Coruh Valley in Turkey, at altitudes of 800 1,150 m. The mean observed number of alleles per locus varied from 2 (loci VVMD7 and VVMD24) to 6 (VVS2) among populations. The population from the highest altitude showed the greatest average number of alleles, 4.5. With regard to the six loci examined in all populations, the mean observed heterozygosity was higher than the expected heterozygosity. Among the loci, VVS2 (probability of identity = 0.137) was found to be the most informative among populations. Genetic distances between populations ranged from 0.072 to 0.216. Genetic differentiation among populations was strongly related to geographic distances in all populations. PMID- 22298356 TI - An interleukin-10 gene promoter polymorphism (-592A/C) associated with type 2 diabetes: a North Indian study. AB - In this first report on the association of an IL-10 promoter polymorphism with type 2 diabetes mellitus in a North Indian population, the -592A/C SNP (rs1800872) was genotyped by PCR-RFLP and the IL-10 level measured using ELISA. Although no significant difference was observed in the genotypic frequencies (P = 0.657), diabetes patients carried a significantly higher number of A alleles at the -592 position, 25.6% (P < 0.001, odds ratio 0.887, 95% CI 0.670-1.184). Significant correlations were detected in postprandial glucose levels of CC genotype patients and controls (P = 0.025), age and waist-hip ratio of CA patients and controls (P <= 0.001), and fasting glucose (P = 0.045) and low density lipoprotein (P = 0.049) in all patients and controls. The serum IL-10 level was significantly higher in patients than in controls (P = 0.033). The polymorphism was significantly associated with disease incidence and its biochemical manifestations. PMID- 22298357 TI - Genotyping an ALAD polymorphism with real-time PCR in two populations from the Iberian Peninsula. AB - Lead-induced toxicity varies among individuals partly because of genetic differences in their susceptibility to the metal's effects. One genetic polymorphism associated with lead toxicity is a G-to-C transversion at position 177 in the coding region of delta-aminolevulinic acid dehydratase (ALAD), originating from two codominant alleles (ALAD1 and ALAD2). We examined the distribution of this single nucleotide polymorphism in two populations from the Iberian Peninsula. Genomic DNA was extracted from whole blood, and a real-time PCR assay was designed to determine ALAD polymorphic distribution. The distribution of MspI polymorphism was similar in the two populations studied, and allelic frequencies were comparable to those obtained in other studies of Caucasians. Further studies are needed to assess fully the functional significance of this polymorphism and its influence on the toxicokinetics of lead. PMID- 22298358 TI - Decursin inhibits vasculogenesis in early tumor progression by suppression of endothelial progenitor cell differentiation and function. AB - Endothelial progenitor cells (EPCs) contribute to the tumor vasculature during tumor progression. Decursin isolated from the herb Angelica gigas is known to possess potent anti-inflammatory activities. Recently, we reported that decursin is a novel candidate for an angiogenesis inhibitor [Jung et al., 2009]. In this study, we investigated whether decursin regulates EPC differentiation and function to inhibit tumor vasculogenesis. We isolated AC133+ cells from human cord blood and decursin significantly decreased the number of EPC colony forming units of human cord blood-derived AC133+ cells that produce functional EPC progenies. Decursin dose-dependently decreased the cell number of EPC committing cells as demonstrated by EPC expansion studies. Decursin inhibited EPC differentiation from progenitor cells into spindle-shaped EPC colonies. Additionally, decursin inhibited proliferation and migration of early EPCs isolated from mouse bone marrow. Furthermore, decursin suppressed expression of angiopoietin-2, angiopoietin receptor Tie-2, Flk-1 (vascular endothelial growth factor receptor-2), and endothelial nitric oxide synthase in mouse BM derived EPCs in a dose-dependent manner. Decursin suppressed tube formation ability of EPCs in collaboration with HUVEC. Decursin (4 mg/kg) inhibited tumor-induced mobilization of circulating EPCs (CD34 + /VEGFR-2+ cells) from bone marrow and early incorporation of Dil-Ac-LDL-labeled or green fluorescent protein (GFP)+ EPCs into neovessels of xenograft Lewis lung carcinoma tumors in wild-type- or bone-marrow-transplanted mice. Accordingly, decursin attenuated EPC-derived endothelial cells in neovessels of Lewis lung carcinoma tumor masses grown in mice. Together, decursin likely affects EPC differentiation and function, thereby inhibiting tumor vasculogenesis in early tumorigenesis. PMID- 22298359 TI - Pharmacological characterization of the norepinephrine and dopamine reuptake inhibitor EB-1020: implications for treatment of attention-deficit hyperactivity disorder. AB - We report on the pharmacological, behavioral, and neurochemical characterization of a novel dual norepinephrine (NE)/dopamine (DA) transporter inhibitor EB-1020 (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane HCl). EB-1020 preferentially inhibited monoamine reuptake in cloned cell lines transfected with human transporters with IC50 values of 6 and 38, respectively, for NE and DA transporters. In microdialysis studies, EB-1020 markedly increased NE, and DA concentrations levels in rat prefrontal cortex in vivo with peak increases of 375 and 300%, respectively with the greatest effects on NE, and also increased DA extracellular concentrations in the striatum to 400% of baseline concentrations. Behavioral studies demonstrated that EB-1020 dose-dependently decreased immobility in the mouse tail suspension test of depression to 13% of control levels, and did not stimulate locomotor activity in adult rats in the optimal dose range. EB-1020 dose-dependently inhibited locomotor hyperactivity in juvenile rats lesioned with the neurotoxin 6-hydroxydopamine (100 MUg intracisternally) as neonates; a well-established animal model for attention deficit hyperactivity disorder (ADHD). These data suggest that EB-1020 mediates its actions by stimulating NE and DA neurotransmission, which are typically impaired in ADHD. PMID- 22298360 TI - The pros and cons of airway lining fluid composition analysis. PMID- 22298361 TI - Birth cohorts in childhood asthma: lessons and limitations. PMID- 22298362 TI - Vitamin D and chronic obstructive pulmonary disease: justified optimism or false hope? PMID- 22298363 TI - Pharyngeal neuropathy in obstructive sleep apnea: where are we going? PMID- 22298364 TI - Sleep, immunology, and epigenetics: tip of an iceberg. PMID- 22298365 TI - Erdheim chester disease: an unusual fluid overload mimic. PMID- 22298366 TI - Difficult-to-treat asthma or vocal cord dysfunction? PMID- 22298367 TI - mTOR/p70S6K in diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. PMID- 22298368 TI - Camphor, an old cough remedy with a new mechanism. PMID- 22298369 TI - Is there a need to reassess what defines acute kidney injury? PMID- 22298370 TI - Selective decontamination of the digestive tract may reinforce the efficacy of corticosteroids. PMID- 22298371 TI - Polysomnographic findings during wakefulness in Joubert syndrome. PMID- 22298372 TI - Inherent electrochemistry and activation of chemically modified graphenes for electrochemical applications. AB - Graphene research is currently at the frontier of electrochemistry. Many different graphene-based materials are employed by electrochemists as electrodes in sensing and in energy-storage devices. Because the methods for their preparation are inherently different, graphene materials are expected to exhibit different electrochemical behaviors depending on the functionalities and density of defects present. Electrochemical treatment of these "chemically modified graphenes" (CMGs) represents an easy approach to alter surface functionalities and consequently tune the electrochemical performance. Herein, we report a preliminary electrochemical characterization of four common chemically modified graphenes, namely: graphene oxide, graphite oxide, chemically reduced graphene oxide, and thermally reduced graphene oxide. These CMGs were compared with graphite as a reference material. Cyclic voltammetry was used to ascertain the chemical functionalities present and to understand the potential ranges in which the materials were electroactive. Electrochemical treatment with either an oxidative or a reductive fixed potential were then carried out to activate these chemically modified graphenes. The effects of such electrochemical treatments on their electrocatalytic properties were then investigated by cyclic voltammetry in the presence of well-known redox probes, such as [Fe(CN)(6)](4-/3-), Fe(3+/2+), [Ru(NH(3))(6)](2+/3+), and ascorbic acid. Thermally reduced graphene oxide exhibited the best electrochemical behavior amongst all of the CMGs, with the fastest rate of heterogeneous electron transfer (HET) and the lowest overpotentials. These findings will have far-reaching consequences for the evaluation of different CMGs as electrode materials in electrochemical devices. PMID- 22298373 TI - Composites of graphene and other nanocarbons with organogelators assembled through supramolecular interactions. AB - Carbon nanomaterials (CNMs), such as exfoliated graphene (EG), long-chain functionalized EG, single-walled carbon nanotubes (SWNTs), and fullerene (C(60)), have been investigated for their interaction with two structurally different gelators based on all-trans tri-p-phenylenevinylene bis-aldoxime (1) and n lauroyl-L-alanine (2) both in solution and in supramolecular organogels. Gelation occurs in toluene through hydrogen bonding and van der Waals interactions for 1 and 2 in addition to pi-pi stacking specifically in the case of 1. These nanocomposites provide a thorough understanding in terms of molecular-level interactions of dimensionally different CNMs with structurally different gelators. The presence of densely wrapped CNMs encapsulated fibrous network in the resulting composites is evident from various spectroscopic and microscopic studies, indicating the presence of supramolecular interactions. Concentration- and temperature-dependent UV/Vis and fluorescence spectra show that CNMs promote aggregation of the gelator molecules, leading to hypochromism and quenching of the fluorescence intensity. Thermotropic mesophases of 1 are altered by the inclusion of a small amount of CNMs. The gel-CNM composites show increased electrical conductivity compared with that of the native organogel. Rheological studies of the composites demonstrate the formation of rigid and viscoelastic solidlike assembly due to reinforced aggregation of the gelators on CNMs. Synergistic behavior is observed in case of the composite gel of 1, containing a mixture of EG and SWNT, when compared with other mixtures of CNMs in all combinations with EG. This affords new nanocomposites with interesting optical, thermal, electrical, and mechanical properties. PMID- 22298374 TI - Mediastinal seminoma: a case report with special emphasis on SALL4 as a new immunocytochemical marker. AB - Cytological diagnosis is a valuable method for detection of mediastinal tumors, and recent reports have shown the usefulness of fine-needle aspiration cytology for diagnosis of mediastinal tumors, including germ cell tumors. We report a case of mediastinal seminoma diagnosed intraoperatively by cytological examination of cystic fluid containing tumor cells. An anterior mediastinal tumor with cystic component was incidentally found in a 28-year-old Japanese male. Cytological examination of the cystic fluid at the time of tumor resection showed single and loose aggregates of large round to polygonal cells with large round nuclei, vesicular chromatin and nucleoli, and mild to moderate amounts of PAS-positive cytoplasm admixed with mature lymphocytes. A diagnosis of seminoma was made intraoperatively. On subsequent immunostaining, the tumor cells showed nuclear positivity for SALL4, a recently recognized germ cell marker that, in the appropriate setting, can be helpful to distinguish germ cell tumors from other mediastinal neoplasms, such as malignant lymphoma, thymoma, and thymic carcinoma. PMID- 22298375 TI - In vivo remineralization of acid-etched enamel in non-brushing areas as influenced by fluoridated orthodontic adhesive and toothpaste. AB - This study aimed to evaluate the in vivo remineralization of acid-etched enamel in non-brushing areas as influenced by fluoridated orthodontic adhesive and toothpaste. One hundred and twenty teeth from 30 volunteers were selected. The teeth were assigned to four treatments: no treatment (negative control); 37% phosphoric acid-etching (PAE) (positive control); PAE + resin-modified glass ionomer cement (RMGIC); and, PAE + composite resin. Patients brushed teeth with fluoridated (n = 15) or non-fluoridated (n = 15) toothpastes, so that etched enamel was protected with screens and it was not in contact with the brush bristles. Remineralization was evaluated by means of laser fluorescence (LF), environmental scanning electronic microscopy, and energy dispersive spectrometry after extraction. The LF means were compared by means of Wilcoxon and Mann Whitney tests. Environmental scanning electron microscopy scores were compared among the groups using a Kruskal Wallis test, whereas the Ca/P ratio was evaluated by means of an Analysis of Variance with subparcels (treatments) and Tukey's post-hoc test. There were no statistically significant differences between the tooth pastes and between the orthodontic adhesives evaluated. Most teeth presented only partial enamel remineralization. Therefore, the fluoride released by the RMGIC was not enough to cause increased crystal regrowth in the acid-etched enamel. The use of fluoridated toothpaste did not provide positive additional effect. PMID- 22298376 TI - Unprecedented organoimido-derivatised lacunary polyoxometalates. PMID- 22298377 TI - Gold-catalyzed oxidative cyclizations of cis-3-en-1-ynes to form cyclopentenone derivatives. PMID- 22298378 TI - H2O2-aided seed-mediated synthesis of silver nanoplates with improved yield and efficiency. PMID- 22298379 TI - Adenosine A2A receptors modulate glutamate uptake in cultured astrocytes and gliosomes. AB - Glutamate is the primary excitatory neurotransmitter in the central nervous system, where its toxic build-up leads to synaptic dysfunction and excitotoxic cell death that underlies many neurodegenerative diseases. Therefore, efforts have been made to understand the regulation of glutamate transporters, which are responsible for the clearance of extracellular glutamate. We now report that adenosine A(2A) receptors (A(2A) R) control the uptake of D-aspartate in primary cultured astrocytes as well as in an ex vivo preparation enriched in glial plasmalemmal vesicles (gliosomes) from adult rats, whereas A(1) R and A(3) R were devoid of effects. Thus, the acute exposure to the A(2A) R agonist, CGS 21680, inhibited glutamate uptake, an effect prevented by the A(2A) R antagonist, SCH 58261, and abbrogated in cultured astrocytes from A(2A) R knockout mice. Furthermore, the prolonged activation of A(2A) R lead to a cAMP/protein kinase A dependent reduction of GLT-I and GLAST mRNA and protein levels, which leads to a sustained decrease of glutamate uptake. This dual mechanism of inhibition of glutamate transporters by astrocytic A(2A) R provides a novel candidate mechanism to understand the ability of A(2) (A) R to control synaptic plasticity and neurodegeneration, two conditions tightly associated with the control of extracellular glutamate levels by glutamate transporters. PMID- 22298380 TI - Synthesis of olive-shaped mesoporous platinum nanoparticles (MPNs) with a hard templating method using mesoporous silica (SBA-15). AB - Well-ordered mesoporous Pt nanoparticles (MPNs) with uniform olive shapes are synthesized by using two-dimensional (2D) hexagonal mesoporous silica (SBA-15) as a hard template. The average particle sizes are controllable in the range of 150 to 230 nm by changing the reduction time. Low-angle XRD profiles for the obtained MPNs show three distinct peaks assignable to the (10), (11), and (20) planes of a highly ordered 2D hexagonal symmetry. From high-magnification SEM images, periodically arranged Pt nanowires are observed clearly, which are a negative replica of the 2D hexagonally ordered mesoporous silica (SBA-15). Furthermore, the single crystallinity of the Pt fcc structure coherently extends over the whole particles. As a result of such unique character as well as high surface area, the obtained MPNs show distinctly enhanced electrocatalytic properties for methanol oxidation reaction compared to other Pt samples, such as Pt black. PMID- 22298381 TI - C-H/pi-interaction-guided self-assembly in pi-conjugated oligomers. AB - We report CH/pi hydrogen-bond-driven self-assembly in pi-conjugated skeletons based on oligophenylenevinylenes (OPVs) and trace the origin of interactions at the molecular level by using single-crystal structures. OPVs were designed with appropriate pendants in the aromatic core and varied by hydrocarbon or fluorocarbon tails along the molecular axis. The roles of aromatic pi-stack, van der Waals forces, fluorophobic effect and CH/pi interactions were investigated on the theromotropic liquid crystallinity of OPV molecules. Single-crystal structures of hydrocarbon OPVs provided direct evidence for the existence of CH/pi interactions between the pi-ring (H-bond acceptor) and alkyl C-H (H-bond donor). The four important crystallographic parameters, d(c-x)=3.79 A, theta=21.49 degrees , phi=150.25 degrees and d(Hp-x)=0.73 A, matched in accordance with typical CH/pi interactions. The CH/pi interactions facilitate the close-packing of mesogens in x-y planes, which were further protruded along the c axis producing a lamellar structure. In the absence of CH/pi interactions, van der Waals interactions drove the assembly towards a Schlieren nematic texture. Fluorocarbon OPVs exhibited smectic liquid-crystalline textures that further underwent Smectic A (SmA) to Smectic C (SmC) phase transitions with shrinkage up to 11%. The orientation and translational ordering of mesogens in the liquid crystalline (LC) phases induced H- and J-type molecular arrangements in fluorocarbon and hydrocarbon OPVs, respectively. Upon photoexcitation, the H- and J-type molecular arrangements were found to emit a blue or yellowish/green colour. Time-resolved fluorescence decay measurements confirmed longer lifetimes for H-type smectic OPVs relative to that of loosely packed one-dimensional nematic hydrocarbon-tailed OPVs. PMID- 22298382 TI - Malignant biphasic peritoneal mesothelioma in a child: consideration of other diagnostic possibilities. PMID- 22298383 TI - Cooperative catalytic reactions using distinct transition-metal catalysts: ruthenium- and copper-catalyzed enantioselective propargylic alkylation. AB - The enantioselective propargylic alkylation of propargylic alcohols with beta ketoesters in the presence of a thiolate-bridged diruthenium complex and a copper complex as co-catalyst affords the corresponding propargylic alkylated products in excellent yields as a mixture of two diastereoisomers with high enantioselectivity (up to 95% enantiomeric excess (ee)). The findings reported herein not only open up a new type of enantioselective propargylic substitution reaction, but also a new aspect of cooperative catalytic reactions using distinct transition metals to realize a useful transformation that cannot be achieved by a single catalyst. PMID- 22298385 TI - Real-time deformation of colon and endoscope for colonoscopy simulation. AB - BACKGROUND: Colonoscopy simulation has been increasingly applied as a method of training, which can supplement the traditional patient-based training in recent years. However, the current level of realism of the simulation is insufficient. One of the main difficulties degrading the realism is real-time simulation of colon deformation involving multi-contact interaction with the endoscope. METHODS: This paper proposes a novel simulation framework for real-time deformation of the colon and endoscope, using a skeleton-driven deformation method. Cylindrical lattices and a centre-line are employed as the skeletons, and a mass-spring model is applied to the skeletons for the mechanics-based simulation. The centre-line-based collision detection and resolution algorithm is proposed to simulate the interaction between the colon and endoscope. A haptic rendering algorithm using the energy method is proposed to produce feedback force, based on physical interaction between the colon and endoscope. RESULTS: The proposed simulation framework has been implemented and evaluated in colonoscopy simulation. The simulation results show that the proposed method allows real-time simulation (28 Hz) using a colon model composed of up to 241,440 meshes. CONCLUSIONS: The proposed method allows real-time simulation of colon and endoscope deformation while maintaining a visually plausible result and realistic haptic sensation. PMID- 22298386 TI - ansa-Rare-earth-metal catalysts for rapid and stereoselective polymerization of renewable methylene methylbutyrolactones. AB - Two ansa-half-sandwich rare-earth-metal (REM) dialkyl complexes supported by an ethylene-bridged fluorenyl (Flu)-N-heterocyclic carbene (NHC) ligand, [M{C(2)H(4)(eta(5)-Flu-kappa(1)-NHC)}(CH(2)SiMe(3))(2)] (M=Y, 1; Lu, 2), and a chiral ansa-sandwich samarocene incorporating a C(2) ligand, [Sm(eta(5) C(12)H(8))(2)(thf)(2)] (3), have been investigated for the coordination-addition polymerization of renewable methylene butyrolactones, alpha-methylene-gamma butyrolactone (MBL) and gamma-methyl-alpha-methylene-gamma-butyrolactone ((gamma)MMBL). Both ansa-half-sandwich complexes 1 and 2 exhibit exceptional activity for the polymerization of (gamma)MMBL at room temperature in dimethylformamide (DMF); with a 0.25 mol% catalyst loading, quantitative monomer conversion can be achieved under 1 min, giving a high turn-over frequency (TOF) of 24,000 h(-1). This TOF value represents a rate enhancement, by a factor of 8, 22, or 2400, over the polymerizations by unbridged samarocene [Sm(Cp*)(2)(thf)(2)] (Cp*=eta(5) -pentamethylcyclopentadienyl), by bridged ansa samarocene 3 with C(2) ligation, or by the corresponding REM trialkyls without the ansa-Flu-NHC ligation, respectively. Complexes 1 and 2 are also highly active for the polymerization of beta-methyl-alpha-methylene-gamma-butyrolactone ((beta)MMBL), realizing the first example of the metal-mediated coordination polymerization of this monomer and its copolymerization with (gamma)MMBL. More remarkably, the resulting P(beta)MMBL homopolymer is highly stereoregular (91% mm) and exhibits a high T(g) of 290 degrees C. In sharp contrast, catalysts 1 and 2 have poor activity and efficiency in the polymerization of the parent MBL or the acyclic analog methyl methacrylate. Polymerization and kinetic studies using the most active catalyst (1) of the series have uncovered characteristics of its (gamma)MMBL polymerization and yielded a unimolecular propagation mechanism. A surprising chain-initiation pathway for the polymerization in DMF by 1 has been revealed, and catalytic polymerization in the presence of an organoacid has also been examined. PMID- 22298387 TI - Efficient synthesis of tetrasubstituted furans from nitroallylic acetates and 1,3 dicarbonyl/alpha-activating ketones by Feist-Benary addition-elimination. PMID- 22298388 TI - Effects of anti-CD3 monoclonal antibody in salivary glands of spontaneously diabetic mice. AB - BACKGROUND: Diabetes mellitus results in many complications, also compromising the salivary glands. The current treatment for this condition should be a substituting method to exogenous insulin. In this aspect, the immunotherapy has been tested, but, it can be inefficient as an agent for the control of damage caused by diabetes. Thus, the aim of this study was to evaluate the anti-CD3 monoclonal antibody as alternative immunotherapy in the recovery of salivary glands of spontaneously diabetic NOD (nonobese diabetic) mice. METHODS: NOD mice were divided into two groups of 10 animals: group I (untreated diabetic mice) and group II (anti-CD3-treated diabetic mice). After treatment, the samples of salivary glands were collected for histological examination under both transmitted and polarized light microscopy. RESULTS: Alterations in tissue architecture; increase in extracellular matrix and presence of inflammatory process were observed in untreated animals. Recovery of the salivary acinar cells occurred in treated animals. The parotid glands demonstrated a smaller amount of collagen fibers and were not observed severe inflammatory processes. CONCLUSION: These results indicate that immunotherapy contributed to reestablishment of tissue damaged by the hyperglycemic condition, demonstrating that the immunomodulation plays an important role in the recovery of salivary glands. PMID- 22298389 TI - Nutritional outcomes following gastrostomy in children with cystic fibrosis. AB - OBJECTIVE: In 2005 the Cystic Fibrosis (CF) Foundation recommended that children with CF maintain a body mass index (BMI) >= 50th percentile. Our study evaluated if gastrostomy (GT) placement increases the likelihood of reaching that goal compared to a standardized nutrition protocol. STUDY DESIGN: Retrospective study of 20 children with CF ages 2-20 years with GTs placed from 2005 to 2010. Each case was pair-matched on age, sex, pancreatic status, BMI, and lung function with a nonGT child with CF. Outcome measures included nutritional status and lung function at 6 months and 1 year. RESULTS: At baseline, mean +/- SD BMI Z-scores were similar (cases -1.19 +/- 0.60, controls -1.10 +/- 0.50; P = 0.10). Cases had a significant 6-month increase in mean BMI Z-score to -0.29 +/- 0.84 compared to 1.02 +/- 0.67 for controls (P < 0.001). By 1 year, the change in mean BMI Z-score was less different (cases -0.41 +/- 0.76, controls -0.71 +/- 0.51; P = 0.07). Both groups had stable lung function. From exact logistic regression analysis, the odds ratio for cases compared to controls of reaching BMI >= 50th percentile was 9.70 (95% CI: 1.05-484.7; P = 0.04) at 6 months and 3.65 (95%CI: 0.69-25.86; P = 0.16) at 1 year. CONCLUSION: Our study suggests that children with CF who receive GTs are more likely to achieve BMI >= 50th percentile than matched children without GTs. PMID- 22298390 TI - Predictive factors for inadequate stem cell mobilization in Chinese patients with NHL and HL: 14-year experience of a single-center study. AB - BACKGROUND: Factors affecting progenitor cell mobilization in patients with non Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) are incompletely understood. The aim of this retrospective study was to determine which factors are crucial for effective mobilization and collection of autologous peripheral blood stem cells (PBSC) prior to transplantation in Chinese patients. PATIENTS AND METHODS: A total of 239 patients with lymphoma (198 NHL and 41 HL patients) underwent PBSC collection after mobilization with granulocyte-colony-stimulating factor (G-CSF) or G-CSF plus chemotherapy priming. RESULTS: Patient characteristics at diagnosis and transplant, including low Eastern Cooperative Oncology Group score (P = 0.013), lack of extranodal invasion (P = 0.034), previously administered radiotherapy regimens (P = 0.040), treatment with platinum prior to mobilization (P = 0.042), previous chemotherapy regimens (P = 0.001) and cycles (P < 0.001), and chemotherapy regimens (P < 0.001) were statistically significant for successful mobilization in multivariate analysis. Premobilization factors, including previous radiotherapy (P = 0.009), previous chemotherapy regimens (P = 0.043) and cycles (P = 0.039), low platelet count prior to mobilization (P = 0.042), and lower CD34+ cells in peripheral blood (PB) (P = 0.050) or bone marrow (BM) (P = 0.007) were considered possibly predictive of poor mobilization. We found the patients who had chemosensitive lymphoma had worse progress-free survival (PFS) than the patients with initial treatment and high risks (P = 0.017). CONCLUSION: Our analysis showed that high amounts of chemotherapy, radiotherapy, low platelet count, chemosensitive recurrent patients, combination chemotherapy plus G-CSF and low CD34+ cells in BM prior to mobilization could emerged as important predictive factors for mobilization failure in Chinese patients with NHL and HL. PMID- 22298392 TI - Psychopharmacological imaging. PMID- 22298391 TI - ATP-P2X7 receptor signaling controls basal and TNFalpha-stimulated glial cell proliferation. AB - Activation and proliferation of glial cells and their progenitors is a key process of neuroinflammation associated with many neurodegenerative disorders. Under neuropathological conditions where glial cell activation and proliferation is evident, controlling the population of glia might be of therapeutic importance. The proliferative action of the cytokine tumor necrosis factor alpha (TNFalpha) on microglia has been reported, but the molecular mechanism of TNFalpha regulation of glial cell proliferation is largely unknown. Using a model of organotypic hippocampal-entorhinal cortex (HEC) slice culture, we investigated the role of ATP-P2X(7) receptor signaling in glial proliferation by TNFalpha. Populations of proliferating cells in HEC culture were labeled with 5-bromo-2' deoxyuridine (BrdU). Treatment with TNFalpha induced strong expression of P2X(7) receptor mRNA and immunoreactivity in BrdU+ cells while markedly increasing proliferation of BrdU+ cells. In addition, TNFalpha increased aquaporin 4 (AQP4) expression, an ion channel involved in glial proliferation. The proliferative action of TNFalpha was attenuated by blocking the P2X(7) receptors with the specific antagonists oxATP, BBG, and KN62, or by lowering extracellular ATP with ATP hydrolysis apyrase. Basal proliferation of BrdU+ cells was also sensitive to blockade of ATP-P2X(7) signaling. Furthermore, TNFalpha activation of P2X(7) receptors appear to regulate AQP4 expression through protein kinase C cascade and down regulation of AQP4 expression can reduce TNFalpha-stimulated BrdU+ cell proliferation. Taken together, these novel findings demonstrate the importance of ATP-P2X(7) signaling in controlling proliferation of glial progenitors under the pathological conditions associated with increased TNFalpha. PMID- 22298393 TI - A new human (psycho)pharmacology tool: the multiple organs coincidences counter (MOCC). AB - We describe a novel instrument which is capable of measuring the uptake of radioligand in human organs in vivo with the administration of very small doses of positron-emitting radioligands. This technique readily detects the displacement or reduced uptake of radioligand when a competitive agonist or antagonist is administered. This system provides no tomographic information, but the small radioactive doses involved mean that investigations can be repeated at regular intervals and that female volunteers can also participate. We administered [(11) C]flumazenil, [(11)C]diprenorphine, [(11)C]meta hydroxyephedrine (MHED) and [(11)C]RTI 55 to healthy male volunteers and performed control, pre-loading and displacement experiments. These demonstrate the feasibility of using this technique to investigate benzodiazepine and opiate receptor occupancy, as well as occupancy at dopamine, noradrenaline and serotonin (5-HT) re-uptake sites. This method is likely to be useful in pharmacokinetic/pharmacodynamic experiments, in drug development and discovery and in the development of novel imaging radioligands. PMID- 22298394 TI - Menstrual cycle effects on the action of buspirone on food intake in healthy female volunteers. AB - We studied the effect of single doses of the 5-HT(1A) agonist buspirone (10 mg and 20 mg) on food intake during the menstrual cycle of nine healthy women, none of whom were on a contraceptive pill. In a double-blind placebo-controlled trial, subjects were tested over three cycles, receiving one treatment per cycle. Within each cycle, they were tested at two time points; mid-follicular and late luteal. Food intake following 20 mg buspirone was significantly higher in the luteal phase, suggesting the possibility of pre-menstrually enhanced 5-HT receptor sensitivity. PMID- 22298395 TI - Impairment of performance associated with long-term use of benzodiazepines. AB - The long-term effects of benzodiazepines (BDZ) on psychomotor and cognitive functions were assessed in 28 out patients, users of low therapeutic doses of diazepam (13.6 +/- 4.9 mg/day, range: 5-20 mg/day) for 5-20 years (10.1 +/- 5.0 years). These patients' performance was compared with two control groups: 53 BDZ free anxious out patients and 56 healthy volunteers. The three groups were similar in sex, age and education. BDZ chronic users were tested before and after short-term (3 weeks) and long-term discontinuation (at an average of 10 months). Performance of chronic users of BDZ was consistently worse than those of the control groups, suggesting an impairment in these patients on both psychomotor and cognitive functions. These were not related to either dose or cumulative exposure to BDZ, and were also independent of diagnosis and levels of anxiety and depression. Moreover, these deficits were persistent as their performance failed to improve after drug discontinuation. PMID- 22298396 TI - A comparison of age-related deficits in memory and frontal lobe function following oral lorazepam administration. AB - Differential responses on cognitive function of young (18-45 years, n = 17) and elderly (60-75 years, n = 9) subjects were compared before and after a challenge with lorazepam (2 mg oral) or placebo. Tests of memory and frontal lobe function were administered to determine the specificity of the amnesic deficit produced and the interaction of drug and the aging brain. Anterograde amnesia, as assessed by recall of a word list, was noted in both groups and was greater in the elderly. Whereas lorazepam produced only impaired recall in the young group, the elderly group manifested a further range of cognitive impairments, including decreased verbal fluency on the controlled oral word association test and reduced performance on the Wisconsin card-sorting test. These impairments in the elderly group could not be attributed to performance deficits pre-drug. Short-term memory, as evidenced by digit span and the copy trial of the Rey figure, was not impaired by lorazepam. It is concluded that whilst lorazepam produces a relatively 'pure' amnesia in young to middle aged adults, in the elderly there is an admixture of deficits in some frontal lobe functions. This is presumed to reflect age-related changes in the brain and may be analogous to the spectrum of results noted in Korsakoff's psychosis as opposed to 'pure' diencephalic amnesia. PMID- 22298397 TI - Similar effects of buspirone and chlordiazepoxide on a fixed interval schedule with long-term, low-dose administration. AB - Buspirone is a novel anxiolytic which does not share the muscle relaxant, anticonvulsant and sedative properties of classical anxiolytics such as the benzodiazepines. Its effects on behavioural tests of anxiolytic action generally match those of classical anxiolytics provided a low dose is used. However, in a previous experiment, buspirone appeared to affect fixed interval responding in a way which differed qualitatively as well as quantitatively from the classical anxiolytic chlordiazepoxide. It takes as much as 2 weeks for the clinical effects of anxiolytics to develop, during which time the side effects of benzodiazepines undergo tolerance. We, therefore, decided to compare long-term pre-administration (60 days, three injections/day) of buspirone and chlordiazepoxide on learning of a fixed interval 60-s schedule. The doses were based on previous acute dose response tests of hippocampal theta rhythm in freely moving animals. Buspirone (0.1 mg/ kg i.p.) and chlordiazepoxide (0.4 mg/kg i.p.) produced similar increases in responding, especially in the middle of acquisition of the fixed interval schedule. Consistent with our acute electrophysiological tests, the effects of 0.4 mg/kg chlordiazepoxide were somewhat larger than those of 0.1 mg/kg buspirone. These results suggest that the acute effects of buspirone, but probably not chlordiazepoxide, on fixed interval responding are contaminated by side effects which do not seriously affect the results with long-term administration. The effects of both novel and classical anxiolytics on control of hippocampal theta rhythm appear to predict the magnitude of their common anxiolytic effects and to be unrelated to their different side effects. PMID- 22298398 TI - Buspirone treatment as an aid to benzodiazepine withdrawal. AB - Twenty four long-term benzodiazepine users were allocated randomly to treatment with either buspirone (mean dose 25 mg/day) or placebo, prior to tapering off the benzodiazepine over 6 weeks. In both groups, six out of 12 patients successfully completed withdrawal. However, buspirone-treated patients tended to have lower anxiety levels than placebo-treated patients. The amount of previous benzodiazepine usage predicted outcome. PMID- 22298399 TI - The effects of a low tryptophan diet on brain 5 -HT metabolism and 5-HT-mediated neuroendocrine responses in the male rat. AB - The study was undertaken to assess the effects of periods of dietary tryptophan (TRP) depletion on (i) plasma total and free TRP together with brain TRP, 5 hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5- HIAA) and (ii) the prolactin (PRL) responses to the 5-HT releasing agent, D-fenfluramine (FEN), and the 5-HT agonist, m-chlorophenylpiperazine (mCPP). The TRP-deficient diet caused significant reductions in plasma total and free TRP for a short-lived period; however, it caused longer lasting and significant reductions in brain TRP, 5-HT and 5-HIAA content. Following periods of dietary TRP depletion, plasma PRL responses to FEN were significantly reduced for 14 days but had normalised by day 21. In contrast, the PRL responses to mCPP were significantly enhanced after 6 and 21 days, the response at 14 days being similar to control. The result suggests that periods of dietary invoked TRP depletion cause a deficiency of brain TRP content which subsequently leads to a fall in brain 5-HT. This is associated with a reduced PRL response to FEN and an enhanced PRL response to mCPP, the latter possibly resulting from functional up-regulation of post synaptic 5-HT receptors. PMID- 22298400 TI - The 5 -HT3 receptor antagonists, granisetron and ondansetron, do not affect cocaine-induced shifts in intra-cranial self-stimulation thresholds. AB - The effects of the 5-HT( 3) receptor antagonists, granisetron and ondansetron, were investigated on behaviour maintained by intracranial self-stimulation (ICSS). Rats, implanted with bipolar electrodes in the lateral hypothalamus, were trained to lever press on a continuous reinforcement schedule for positively reinforcing trains of electrical stimulation. The frequency at which responding reached 50% of maximum (M50) and the maximum rate of responding (asymptote) were used to measure drug effects. Granisetron (0.01-0.1 mg/kg i.p ) and ondansetron (0.03-0.3 mg/kg i.p ) had no effect on either parameter. In contrast, cocaine (20 mg/kg i.p ) potentiated rewarded responding, reducing M50 values, but neither granisetron (0.01-3.0 mg/kg i.p ) nor ondansetron (0.03-0.3 mg/kg i.p ) blocked this effect. Neither did granisetron (0.1-10.0 mg/kg i.p ) alter the effect of lower doses of cocaine (10 mg/kg i.p.). These data suggest that 5 -HT( 3) receptors do not play a significant role in mediating responding maintained by ICSS in the rat through hypothalamic electrodes. Neither do they modulate cocaine induced potentiation of the behaviour. PMID- 22298401 TI - Anxiogenic activity of intraventricularly administered bradykinin in rats. AB - The anxiogenic action of bradykinin was investigated in rats and compared with that of yohimbine, a known anxiogenic agent. Bradykinin (0.5, 1 and 2 MUg/rat) was administered intracerebroventricularly (i.c.v.), whereas yohimbine (2 mg/kg) was administered i.p. The experimental methods used were the open- field, elevated plus-maze, social interaction and novelty suppressed feeding latency tests, and estimation of brain tribulin activity in terms of endogenous monoamine oxidase (MAO) A and MAO B inhibition. The behavioural and biochemical effects induced by bradykinin were qualitatively similar to those of yohimbine. Thus, both the drugs reduced ambulation and rears, and increased immobility and defecation, in the open-field test. They decreased the number of entries and time spent on the open arms of the elevated plus-maze, reduced social interaction in paired rats and increased the feeding latency in an unfamiliar environment in 48 h food-deprived rats. These effects are known to be associated with anxiety in animals. Bradykinin and yohimbine increased rat brain tribulin activity, the effect on the MAO A inhibitor component being more marked than that on the MAO B inhibitor component. The MAO A inhibitor component has been postulated to be the major anxiogenic moiety of tribulin. Lorazepam, a well known benzodiazepine anxiolytic agent, attenuated the anxiogenic effects of bradykinin and yohimbine, which may not be a functional effect. The investigation indicates that, like cholecystokinin (CCK), bradykinin may function as an endogenous anxiogenic peptide. PMID- 22298402 TI - Benzodiazepine receptors and positron emission tomography: ten years of experience. A new beginning? PMID- 22298403 TI - Central benzodiazepine receptor imaging and quantitation with single photon emission computerised tomography: SPECT. AB - This review discusses the current use of single photon emission computerised tomography (SPECT) for central benzodiazepine receptor imaging and quantitation. The general principles underlying SPECT imaging and receptor quantitation methods such as the kinetic, pseudo-equilibrium and steady-state (tracer infusion and bolus) approaches are described. The advantages and practical drawbacks of these techniques are highlighted. PMID- 22298404 TI - Recurrent pancreatitis on clozapine re-challenge. PMID- 22298405 TI - Compressed opiate withdrawal syndrome and naltrexone. AB - The oral opiate antagonist naltrexone is in regular use in clinical practice with abstinent opiate-dependent individuals. Acute opioid withdrawal is a well recognised consequence of consuming naltrexone while opiate dependent. Two cases of naltrexone-induced opiate withdrawal are reported. The compressed nature of the withdrawal syndrome in both of these cases and the implications for the management of protracted withdrawal symptoms are discussed. The theoretical implications of this experimental and clinical phenomenon are reviewed. PMID- 22298406 TI - Detoxified alcoholics, major depressives and tyramine sulphate excretion. AB - The excretion of tyramine sulphate after challenge with an oral load of tyramine was assessed in recently detoxified, clinically depressed alcoholics and a matched group of major depressives. Tyramine excretion in the alcohol group (mean 5.95 +/- 3.28 mg/3 h SD) was in the range previously observed in controls and was significantly higher than in the matched depressives (mean 3.43 +/- 2.37 mg/3 h SD). Tyramine sulphate excretion has been suggested as a genetic vulnerability marker for major depression. This study suggests that depression associated with alcohol withdrawal is not characterised by decreased tyramine sulphate excretion after oral tyramine challenge, such decreased conjugation only being present, perhaps, in those patients with pre- existing endogenous depressive vulnerability. Although a genetic link between alcoholism and depression exists, these results support the absence of such a link to major depression. PMID- 22298407 TI - Psychoactive drugs of use and abuse: wobble, rave, inhale or crave? Symposium organised by the Psychobiology Section, at the British Psychological Society Annual Conference, University of Warwick, UK; 2nd April 1995: Convenors: Dr Andy Parrott, Department of Psychology, University of East London, London E15 4LZ Dr Martin Yeomans, Department of Experimental Psychology, University of Sussex, Sussex BN1 9DG. PMID- 22298408 TI - The origins of mental health-oriented neuroscience in Britain. PMID- 22298409 TI - Obituary Michael shepherd 1923-1995. PMID- 22298410 TI - Protocatechuic aldehyde inhibits lipopolysaccharide-induced human umbilical vein endothelial cell apoptosis via regulation of caspase-3. AB - Apoptosis of vascular endothelial cells results in the loss of endothelial integrity, and is a risk factor of atherosclerosis (AS). Lipopolysaccharide (LPS) stimulates inflammation during AS. The current study examined the effect of a potent water-soluble antioxidant, protocatechuic aldehyde (PCA; derived from the Chinese herb Salvia miltiorrhiza) on apoptosis in human umbilical vein endothelial cells (HUVECs) stimulated with LPS. The LPS (15 ug/ml) stimulation for 30 h resulted in significant HUVEC apoptosis, as detected by Hoechst 33258 staining and Annexin V analysis. The PCA (0.25-1.0 mmol/L, 12 h) inhibited LPS induced HUVEC apoptosis in a dose-dependent manner. Lipopolysaccharide induced caspase-3 activation, but had no significant effect on caspase-2, Bcl-2/Bax, cytochrome c, caspase-9 and granzyme B expression. Protocatechuic aldehyde (0.25 1.0 mmol/L) significantly inhibited caspase-3 activation in a dose-dependent manner. A specific caspase-3 inhibitor also protected against LPS-induced apoptosis; however, no cooperative effect of PCA and the inhibitor was observed in this study. Collectively, these results indicate that PCA inhibits LPS-induced apoptosis in HUVECs through a mechanism that involves caspase-3. PMID- 22298411 TI - Rhodium dinaphthocyclooctatetraene complexes: synthesis, characterization and catalytic activity in [5+2] cycloadditions. AB - Rh COT in the act: a Ni(0)-catalyzed [2+2+2+2] cycloaddition provides a high yielding, scalable synthesis of the ligand dinaphtho[a,e]cyclooctatetraene (dnCOT). dnCOT complexation with Rh(I) gives [Rh(dnCOT)(MeCN)(2)]SbF(6), an excellent catalyst for [5+2] cycloadditions of vinylcyclopropanes and pi-systems with impressive functional group compatibility. PMID- 22298412 TI - In vitro three-dimensional aortic vasculature modeling based on sensor fusion between intravascular ultrasound and magnetic tracker. AB - BACKGROUND: It is desirable to reduce aortic stent graft installation time and the amount of contrast media used for this process. Guidance with augmented reality can achieve this by facilitating alignment of the stent graft with the renal and mesenteric arteries. METHODS: For this purpose, a sensor fusion is proposed between intravascular ultrasound (IVUS) and magnetic trackers to construct three-dimensional virtual reality models of the blood vessels, as well as improvements to the gradient vector flow snake for boundary detection in ultrasound images. In vitro vasculature imaging experiments were done with hybrid probe and silicone models of the vasculature. RESULTS: The dispersion of samples for the magnetic tracker in the hybrid probe increased less than 1 mm when the IVUS was activated. Three-dimensional models of the descending thoracic aorta, with cross-section radius average error of 0.94 mm, were built from the data fusion. CONCLUSION: The development of this technology will enable reduction in the amount of contrast media required for in vivo and real-time three-dimensional blood vessel imaging. PMID- 22298413 TI - Highly efficient 1,4-addition of aldehydes to nitroolefins: organocatalysis in continuous flow by solid-supported peptidic catalysts. PMID- 22298414 TI - Synthesis of polycyclic aromatic hydrocarbon-based nanovehicles equipped with triptycene wheels. AB - Two new nanovehicles that have extended aromatic platforms as the cargo zones have been obtained. Two strategies were considered for the formation of the perylene core from two naphthalene precursors. The first was based on a Scholl type reaction involving an oxidant, and the second used a brominated derivative to perform a homocoupling reaction. The first strategy failed under diverse coupling conditions in the presence of several strong oxidants. Nevertheless, the use of CoF(3) in trifluoroacetic acid triggered a dimerization reaction between two ester groups of one molecule and the naphthalene unit of another, thereby surprisingly yielding a ten-membered carbon macrocycle. The second strategy encountered a lack of reactivity of the substrate under several homocoupling conditions. The dimerization was not easily performed but Ullmann-type conditions ultimately gave the expected product. The low yield and low solubility of the product encouraged us to modify our initial design. The synthesis of a new chassis that incorporated additional tert-butyl groups improved the solubility of the molecules and also prevented overcyclization of the aromatic platform by blocking these positions. Some p-phenylene spacers were also intercalated between the iodine and perylene centers to increase the reactivity of the halide towards coupling reactions. Two new chassis were obtained by Scholl-type oxidative coupling using FeCl(3) as the oxidant. The introduction of four triptycene wheels allowed the formation of the two corresponding nanovehicles. PMID- 22298415 TI - Protective effect of Brazilian propolis against hepatic oxidative damage in rats with water-immersion restraint stress. AB - In the present study we examined the protective effect of Brazilian propolis against hepatic oxidative damage in rats with water-immersion restraint stress (WIRS) in comparison with that of vitamin E (VE). Fasted rats orally received Brazilian green propolis ethanol extract (BPEE; 10, 50 or 100 mg/kg), VE (250 mg/kg) or vehicle at 30 min before the onset of WIRS. Exposure of vehicle-treated rats to 6 h of WIRS caused liver cell damage, judging from the levels of serum alanine aminotransferase and aspartate aminotransferease, increased hepatic lipid peroxide, NO(x) contents and myeloperoxidase activity, and decreased hepatic non protein SH, ascorbic acid contents and superoxide dismutase activity. Preadministration of BPEE (50 or 100 mg/kg) or VE to the stressed rats protected against the hepatic damage and attenuated the increased hepatic lipid peroxide and NO(x) contents and myeloperoxidase activity and the decreased hepatic non protein SH and ascorbic acid contents and superoxide dismutase activity. These protective effects of BPEE (50 mg/kg) were greater than those of BPEE (100 mg/kg) and were almost equal to those of VE. These results indicate that BPEE protects against hepatic oxidative damage in rats exposed to WIRS possibly through its antioxidant and antiinflammatory properties such as VE. PMID- 22298416 TI - Iron homeostasis in astrocytes and microglia is differentially regulated by TNF alpha and TGF-beta1. AB - Abnormal iron homeostasis is increasingly thought to contribute to the pathogenesis of several neurodegenerative disorders. We have previously reported impaired iron homeostasis in a mouse model of spinal cord injury and in a mouse model of amyotrophic lateral sclerosis. Both these disorders are associated with CNS inflammation. However, what effect inflammation, and in particular, inflammatory cytokines have on iron homeostasis in CNS glia remains largely unknown. Here we report that the proinflammatory cytokine TNF-alpha, and the anti inflammatory cytokine TGF-beta1 affect iron homeostasis in astrocytes and microglia in distinct ways. Treatment of astrocytes in vitro with TNF-alpha induced the expression of the iron importer "divalent iron transporter 1" (DMT1) and suppressed the expression of the iron exporter ferroportin (FPN). However, TGF-beta1 had no effect on DMT1 expression but increased the expression of FPN in astrocytes. In microglia, on the other hand, both cytokines caused induction of DMT1 and suppression of FPN expression. Iron influx and efflux assays in vitro confirmed that iron homeostasis in astrocytes and microglia is differentially regulated by these cytokines. In particular, TNF-alpha caused an increase in iron uptake and retention by both astrocytes and microglia, while TGF-beta1 promoted iron efflux from astrocytes but caused iron retention in microglia. These data suggest that these two cytokines, which are expressed in CNS inflammation in injury and disease, can have profound and divergent effects on iron homeostasis in astrocytes and microglia. PMID- 22298417 TI - Online cognitive-behavioural treatment of bulimic symptoms: a randomized controlled trial. AB - BACKGROUND: Manualized cognitive-behavioural treatment (CBT) is underutilized in the treatment of bulimic symptoms. Internet-delivered treatment may reduce current barriers. OBJECTIVE: This study aimed to assess the efficacy of a new online CBT of bulimic symptoms. METHOD: Participants with bulimic symptoms (n = 105) were randomly allocated to online CBT, bibliotherapy or waiting list/delayed treatment condition. Data were gathered at pre-treatment, post-treatment and 1 year follow-up. OUTCOME MEASURES: The primary outcome measures were the Eating Disorder Examination Questionnaire (EDE-Q) and the frequency of binge eating and purging episodes. The secondary outcome measure was the Body Attitude Test. RESULTS: Dropout from Internet treatment was 26%. Intention-to-treat ANCOVAs of post-test data revealed that the EDE-Q scores and the frequency of binging and purging reduced more in the online CBT group compared with the bibliotherapy and waiting list groups (pooled between-group effect size: d = 0.9). At 1-year follow up, improvements in the online CBT group had sustained. CONCLUSION: This study identifies online CBT as a viable alternative in the treatment of bulimic symptoms. PMID- 22298418 TI - The effective use of plerixafor as a real-time rescue strategy for patients poorly mobilizing autologous CD34(+) cells. AB - Plerixafor enhances CD34(+) cell mobilization, however, its optimal use is unknown. We hypothesized that plerixafor could "rescue" patients in the midst of mobilization when factors indicated a poor CD34(+) yield. Of 295 consecutive autologous peripheral blood mobilization attempts at our center, 39 (13%) used plerixafor as rescue strategy due to a CD34(+) cell concentration <10/MUl (median 5.95/MUl, n = 30), low CD34(+) cell yield from prior apheresis day (median 1.06 * 10(6) CD34(+) cells/kg, n = 7), or other (n = 2). Patients received a median of one plerixafor dose (range: 1-4). Thirty-four (87%) collected =2 * 10 (6) CD34(+) cells/kg and 26 (67%) collected =4 * 10 (6) CD34(+) cells/kg. Median collections for lymphoma (n = 24) and myeloma (n = 15) patients were 4.1 * 10(6) and 8.3 * 10(6) CD34/kg, respectively. A single dose of plerixafor was associated with an increase in the mean peripheral blood CD34(+) concentration of 17.2 cells/MUl (P < 0.001) and mean increased CD34(+) cell yield following a single apheresis of 5.11 * 10(6) /kg (P < 0.03). A real time rescue use of plerixafor is feasible and may allow targeted use of this agent. J. Clin. Apheresis, 2012. (c) 2012 Wiley Periodicals, Inc. PMID- 22298419 TI - Lung aeration changes after lung recruitment in children with acute lung injury: a feasibility study. AB - RATIONALE: There are several adult studies using computed tomography (CT-scan) to examine lung aeration changes during or after a recruitment maneuver (RM) in ventilated patients with acute lung injury (ALI). However, there are no published data on the lung aeration changes during or after a RM in ventilated pediatric patients with ALI. OBJECTIVE: To describe CT-scan lung aeration changes and gas exchange after lung recruitment in pediatric ALI and assess the safety of transporting patients in the acute phase of ALI to the CT-scanner. METHODS: We present a case series completed in a subset of six patients enrolled in our previously published study of efficacy and safety of lung recruitment in pediatric patients with ALI. INTERVENTION: RM using incremental positive end expiratory pressure. RESULTS: There was a variable increase in aerated and poorly aerated lung after the RM ranging from 3% to 72% (median 20%; interquartile range 6, 47; P = 0.03). All patients had improvement in the ratio of partial pressure of arterial oxygen over fraction of inspired oxygen (PaO(2) /FiO(2)) after the RM (median 14%; interquartile range: 8, 72; P = 0.03). There was a decrease in the partial pressure of arterial carbon dioxide (PaCO(2)) in four of six subjects after the RM (median -5%; interquartile range: -9, 2; P = 0.5). One subject had transient hypercapnia (41% increase in PaCO(2)) during the RM and this correlated with the smallest increase (3%) in aerated and poorly aerated lung. All patients tolerated the RM without hemodynamic compromise, barotrauma, hypoxemia, or dysrhythmias. CONCLUSIONS: Lung recruitment results in improved lung aeration as detected by lung tomography. This is accompanied by improvements in oxygenation and ventilation. However, the clinical significance of these findings is uncertain. Transporting patients in early ALI to the CT-scanner seems safe and feasible. PMID- 22298420 TI - Multiple-site labeling of proteins with unnatural amino acids. PMID- 22298421 TI - Determination of arecoline in areca nut based on field amplification in capillary electrophoresis coupled with electrochemiluminescence detection. AB - A sensitive capillary electrophoresis-electrochemiluminescence (CE-ECL) assay with an ionic liquid (IL) was developed for the determination of arecoline in areca nut. The IL, 1-butyl-3-methylimidazolium tetrafluoroborate (BMImBF(4) ), was an effective additive improved not only the separation selectivity but also the detection sensitivity of the analyte. BMImBF(4) in the separation electrolyte made the resistance of the separation buffer much lower than that of the sample solution, which resulted in an enhanced field amplified electrokinetic injection CE. ECL intensity of arecoline is about two times higher than that of the analyte with phosphate-IL buffer system. Resolution between arecoline and other unknown compounds in real samples was improved. Under the optimized conditions (ECL detection at 1.2 V, 16 kV separation voltage, 20 mmol/L phosphate with 10 mmol/L BMImBF(4) buffer at pH 7.50, 5 mmol/L Ru(bpy)(3)(2+) and 50 mmol/L phosphate buffer in the detection reservoir), a detection limit of 5 * 10(-9) mol/L for arecoline was obtained. Relative standard deviations of the ECL intensity and the migration time were 4.51% and 0.72% for arecoline. This method was successfully applied to determination of the amount of arecoline in areca nut within 450 s. PMID- 22298422 TI - Application of the sol-gel technique to develop synthetic calcium-based sorbents with excellent carbon dioxide capture characteristics. AB - An option for reducing the release of greenhouse gases into the atmosphere is the implementation of CO(2) capture and storage (CCS) technologies. However, the costs associated with capturing CO(2) by using the currently available technology of amine scrubbing are very high. An emerging second-generation CO(2) capture technology is the use of calcium-based sorbents, which exploit the carbonation and calcination reactions of CaO, namely, CaO+CO(2) <->CaCO(3). Naturally occurring Ca-based sorbents are inexpensive, but show a very rapid decay of CO(2) uptake capacity with cycle number. Here, we report the development of synthetic Ca-based CO(2) sorbents using a sol-gel technique. Using this technique, we are able to synthesize a nanostructured material that possesses a high surface area and pore volume and shows excellent CO(2) capture characteristics over many cycles. Furthermore, we are able to establish a clear relationship between the structure of the sorbent and its performance. After 30 cycles of calcination and carbonation, the best material possessed a CO(2) uptake capacity of 0.51 g of CO(2) per gram of sorbent; a value that is about 250 % higher than that for naturally occurring Havelock limestone. PMID- 22298423 TI - Colocalization of Mec1 and Mrc1 is sufficient for Rad53 phosphorylation in vivo. AB - When DNA is damaged or DNA replication goes awry, cells activate checkpoints to allow time for damage to be repaired and replication to complete. In Saccharomyces cerevisiae, the DNA damage checkpoint, which responds to lesions such as double-strand breaks, is activated when the lesion promotes the association of the sensor kinase Mec1 and its targeting subunit Ddc2 with its activators Ddc1 (a member of the 9-1-1 complex) and Dpb11. It has been more difficult to determine what role these Mec1 activators play in the replication checkpoint, which recognizes stalled replication forks, since Dpb11 has a separate role in DNA replication itself. Therefore we constructed an in vivo replication-checkpoint mimic that recapitulates Mec1-dependent phosphorylation of the effector kinase Rad53, a crucial step in checkpoint activation. In the endogenous replication checkpoint, Mec1 phosphorylation of Rad53 requires Mrc1, a replisome component. The replication-checkpoint mimic requires colocalization of Mrc1-LacI and Ddc2-LacI and is independent of both Ddc1 and Dpb11. We show that these activators are also dispensable for Mec1 activity and cell survival in the endogenous replication checkpoint but that Ddc1 is absolutely required in the absence of Mrc1. We propose that colocalization of Mrc1 and Mec1 is the minimal signal required to activate the replication checkpoint. PMID- 22298424 TI - Yos9p and Hrd1p mediate ER retention of misfolded proteins for ER-associated degradation. AB - The endoplasmic reticulum (ER) has an elaborate quality control system, which retains misfolded proteins and targets them to ER-associated protein degradation (ERAD). To analyze sorting between ER retention and ER exit to the secretory pathway, we constructed fusion proteins containing both folded carboxypeptidase Y (CPY) and misfolded mutant CPY (CPY*) units. Although the luminal Hsp70 chaperone BiP interacts with the fusion proteins containing CPY* with similar efficiency, a lectin-like ERAD factor Yos9p binds to them with different efficiency. Correlation between efficiency of Yos9p interactions and ERAD of these fusion proteins indicates that Yos9p but not BiP functions in the retention of misfolded proteins for ERAD. Yos9p targets a CPY*-containing ERAD substrate to Hrd1p E3 ligase, thereby causing ER retention of the misfolded protein. This ER retention is independent of the glycan degradation signal on the misfolded protein and operates even when proteasomal degradation is inhibited. These results collectively indicate that Yos9p and Hrd1p mediate ER retention of misfolded proteins in the early stage of ERAD, which constitutes a process separable from the later degradation step. PMID- 22298425 TI - GPI-anchor synthesis is indispensable for the germline development of the nematode Caenorhabditis elegans. AB - Glycosylphosphatidylinositol (GPI)-anchor attachment is one of the most common posttranslational protein modifications. Using the nematode Caenorhabditis elegans, we determined that GPI-anchored proteins are present in germline cells and distal tip cells, which are essential for the maintenance of the germline stem cell niche. We identified 24 C. elegans genes involved in GPI-anchor synthesis. Inhibition of various steps of GPI-anchor synthesis by RNA interference or gene knockout resulted in abnormal development of oocytes and early embryos, and both lethal and sterile phenotypes were observed. The piga-1 gene (orthologue of human PIGA) codes for the catalytic subunit of the phosphatidylinositol N-acetylglucosaminyltransferase complex, which catalyzes the first step of GPI-anchor synthesis. We isolated piga-1-knockout worms and found that GPI-anchor synthesis is indispensable for the maintenance of mitotic germline cell number. The knockout worms displayed 100% lethality, with decreased mitotic germline cells and abnormal eggshell formation. Using cell-specific rescue of the null allele, we showed that expression of piga-1 in somatic gonads and/or in germline is sufficient for normal embryonic development and the maintenance of the germline mitotic cells. These results clearly demonstrate that GPI-anchor synthesis is indispensable for germline formation and for normal development of oocytes and eggs. PMID- 22298426 TI - Phosphorylation of Stim1 at serine 575 via netrin-2/Cdo-activated ERK1/2 is critical for the promyogenic function of Stim1. AB - The promyogenic cell surface molecule Cdo is required for activation of extracellular signal-regulated kinase (ERK) and nuclear factor of activated T cells c3 (NFATc3) induced by netrin-2 in myogenic differentiation. However, the molecular mechanism leading to NFATc3 activation is unknown. Stromal interaction molecule 1 (Stim1), an internal calcium sensor of the endoplasmic reticulum store, promotes myogenesis via activation of NFATc3. In this study we investigated the functional interaction between Cdo and Stim1 in myogenic differentiation. Overexpression and depletion of Stim1 enhanced or decreased myotube formation, respectively. Of interest, Stim1 protein levels were decreased in Cdo-deficient perinatal hindlimb muscles or primary myoblasts; this correlates with defective NFATc3 activation in Cdo(-/-) myoblasts upon differentiation. Forced activation of NFATc3 by overexpression of calcineurin restored differentiation of Cdo-depleted C2C12 myoblasts. Furthermore, Cdo and Stim1 formed a complex in 293T cells or in differentiating C2C12 myoblasts. The netrin 2-mediated NFATc3 activation was coincident with robust interactions between Cdo and Stim1 in myoblasts and the ERK-mediated Stim1 phosphorylation at serine 575. The serine 575 phosphorylation was enhanced in C2C12 cells upon differentiation, and the alanine substitution of serine 575 failed to restore differentiation of Stim1-depleted myoblasts. Taken together, the results indicate that cell adhesion signaling triggered by netrin-2/Cdo induces Stim1 phosphorylation at serine 575 by ERK, which promotes myoblast differentiation. PMID- 22298427 TI - Roles of putative Rho-GEF Gef2 in division-site positioning and contractile-ring function in fission yeast cytokinesis. AB - Cytokinesis is crucial for integrating genome inheritance and cell functions. In multicellular organisms, Rho-guanine nucleotide exchange factors (GEFs) and Rho GTPases are key regulators of division-plane specification and contractile-ring formation during cytokinesis, but how they regulate early steps of cytokinesis in fission yeast remains largely unknown. Here we show that putative Rho-GEF Gef2 and Polo kinase Plo1 coordinate to control the medial cortical localization and function of anillin-related protein Mid1. The division-site positioning defects of gef2Delta plo1-ts18 double mutant can be partially rescued by increasing Mid1 levels. We find that Gef2 physically interacts with the Mid1 N-terminus and modulates Mid1 cortical binding. Gef2 localization to cortical nodes and the contractile ring depends on its last 145 residues, and the DBL-homology domain is important for its function in cytokinesis. Our data suggest the interaction between Rho-GEFs and anillins is an important step in the signaling pathways during cytokinesis. In addition, Gef2 also regulates contractile-ring function late in cytokinesis and may negatively regulate the septation initiation network. Collectively, we propose that Gef2 facilitates and stabilizes Mid1 binding to the medial cortex, where the localized Mid1 specifies the division site and induces contractile-ring assembly. PMID- 22298428 TI - The Ankrd 13 family of UIM-bearing proteins regulates EGF receptor endocytosis from the plasma membrane. AB - The mechanism of ubiquitin-dependent endocytosis of cell surface proteins is not completely understood. Here we examine the role of the ankyrin repeat domain (Ankrd) 13A, 13B, and 13D proteins, which constitute a functionally unknown family of ubiquitin-interacting motif (UIM)-bearing proteins, in the process. Stimulation of human HeLa cells with epidermal growth factor (EGF) rapidly induced direct binding of Ankrd 13 proteins to ubiquitinated EGF receptor (EGFR) via the UIMs. The binding was inhibited when the Ankrd 13 proteins underwent UIM dependent monoubiquitination, suggesting that their activity is regulated by ubiquitination of themselves. Ankrd 13 proteins bound specifically to Lys-63 linked ubiquitin chains, which was consistent with a previous report that EGFR mainly undergoes Lys-63-linked polyubiquitination. Ankrd 13 proteins were anchored, via the central region and UIMs, to the plasma membrane, where they colocalized with EGFR. Finally, overexpression of wild-type as well as truncated mutant Ankrd 13 proteins strongly inhibited rapid endocytosis of ubiquitinated EGFR from the surface in EGF-treated cells. We conclude that by binding to the Lys-63-linked polyubiquitin moiety of EGFR at the plasma membrane, Ankrd 13 proteins regulate the rapid internalization of ligand-activated EGFR. PMID- 22298429 TI - The coupling between sister kinetochore directional instability and oscillations in centromere stretch in metaphase PtK1 cells. AB - Kinetochores bound to kinetochore microtubules (kMTs) exhibit directional instability in mammalian and other mitotic vertebrate cells, oscillating between poleward (P) and away-from-the-pole (AP) movements. These oscillations are coupled to changes in length of kMTs in a way that maintains a net stretch of the centromere. To understand how sister kinetochore directional instability and kMT plus-end dynamic instability are coupled to oscillations in centromere stretch, we tracked at high resolution the positions of fluorescent kinetochores and their poles for oscillating chromosomes within spindles of metaphase PtK1 cells. We found that the kinetics of P and AP movement are nonlinear and different. By subtracting contributions from the poleward flux of kMTs, we found that maximum centromere stretch occurred when the leading kinetochore switched from depolymerization to polymerization, whereas minimum centromere stretch occurred on average 7 s after the initially trailing kinetochore switched from polymerization to depolymerization. These differences produce oscillations in centromere stretch at about twice the frequency of kinetochore directional instability and at about twice the frequency of centromere oscillations back and forth across the spindle equator. PMID- 22298430 TI - Systematic survey of deubiquitinase localization identifies USP21 as a regulator of centrosome- and microtubule-associated functions. AB - Ubiquitination is a reversible modification that influences a broad range of physiological processes. There are approximately 90 deubiquitinases (DUBs) encoded in the human genome, of which 79 are predicted to have catalytic activity. We tagged 66 DUBs with green fluorescent protein and systematically surveyed their subcellular distribution, identifying enzymes specific to the nucleus, plasma membrane, and secretory and endocytic pathways. USP21 is unique in showing clear association with both centrosomes and microtubules. Using an in vitro assay, we show that microtubule binding is direct and identify a novel microtubule-binding motif encompassed within amino acids 59-75 of the N-terminus of USP21. Our functional studies indicate a key role for USP21 in the governance of microtubule- and centrosome-associated physiological processes: Depletion of USP21 in A549 cells compromises the reestablishment of a radial array of microtubules during recovery from cold-induced depolymerization and also reduces the probability of primary cilium formation, whereas USP21 knockdown in PC12 cells inhibits nerve growth factor-induced neurite outgrowth. PMID- 22298431 TI - Adolescents' reactions after a wildfire disaster in Greece. AB - This cross-sectional study examined the factors associated with higher levels of posttraumatic stress disorder (PTSD) and depression symptoms in 1,468 adolescents, 6 months after a wildfire. The rate of probable PTSD was 29.4% and 20% for probable depression. Findings on predisaster, disaster-related, and postdisaster factors revealed that disaster-related factors-specifically objective and perceived threat to self and others-were associated with symptoms of PTSD but not depression. Predisaster life events, postdisaster losses, and escape-oriented coping strategies were associated with higher levels of both PTSD and depression symptoms, while control-oriented coping and perceived social support were differentially associated with symptoms of and depression. Findings have implications for the assessment and treatment of traumatized and depressed adolescents after a disaster. PMID- 22298432 TI - Transformation of regioregular organotitanium polymers into group 16 heterole containing pi-conjugated materials. AB - Regioregular organometallic polymers with titanacyclopentadiene units, obtained from terminal diynes and a low-valent titanium complex, were subjected to reactions with disulfur dichloride and selenium (I) chloride to give pi conjugated polymers with thiophene and selenophene units in the main chain in 63% and 86% yields. Their number-average molecular weights were estimated as 4300 and 5700, respectively. Both polymers were found to be fully pi-conjugated and their HOMO energy levels were remarkably high (-5.3 eV and -5.0 eV for thiophene- and selenophene-containing polymers, respectively) as supported by their UV-vis absorption spectra and CV analyses. PMID- 22298433 TI - Glucose oxidase/horseradish peroxidase co-immobilized at a CNT-modified graphite electrode: towards potentially implantable biocathodes. PMID- 22298434 TI - The combined predictive effect of patient characteristics and alliance on long term dynamic and interpersonal functioning after dynamic psychotherapy. AB - On the basis of the well-established association between early alliance and outcome, this exploratory study investigated the associations between the therapeutic alliance and long-term outcome, 3 years after treatment termination. In addition to the early alliance, pre-treatment patient characteristics and expectancies that were significantly related to early alliance were included in the statistical analyses. The data are from the First Experimental Study of Transference, a dismantling randomized clinical trial with long-term follow-up. One hundred out-patients who sought psychotherapy due to depression, anxiety and personality disorders were treated. Alliance was measured with Working Alliance Inventory after session 7. Change was determined using linear mixed model analyses. The alliance alone had a significant impact on long-term outcome of the predetermined primary outcome variables of the study: Psychodynamic Functioning Scales and Inventory of Interpersonal Problems. Contrary to common clinical wisdom, when the pre-treatment patient variables were included, more personality disorder pathology was the strongest predictor of favourable outcome, over and above the effect of the alliance, which was no longer significant. Clinical implications are discussed. PMID- 22298435 TI - Current status of additive solutions for platelets. AB - The storage of platelets in additive solution (PAS) had lagged behind red cell concentrates, especially in North America. The partial or complete removal of anticoagulated plasma and storage of platelet concentrates in AS presents many advantages. The PAS can be formulated to optimize aerobic metabolism or decrease platelet activation, thus abrogating the platelet storage lesion and potentially improving in vivo viability. Plasma removal has been shown to reduce allergic reactions and the plasma harvested could contribute to the available plasma pool for transfusion or fractionation. PAS coupled to pathogen reduction technology results in a platelet product of equivalent hemostatic efficacy to conventionally stored platelets. Given the above, the likely future direction of platelet storage will be in new generation designer PAS with an extended shelf life and a superior safety profile to plasma stored platelets. J. Clin. Apheresis, 2012. (c) 2012 Wiley Periodicals, Inc. PMID- 22298436 TI - Palladium-catalyzed intermolecular C(sp3)-H amidation. PMID- 22298437 TI - Flow-injection chemiluminescence determination of haemoglobin in the blood. AB - In this study, a sensitive and simple flow-injection chemiluminescence (CL) method was developed for the quantitative analysis of haemoglobin. The method is based on the ability of haemoglobin to enhance the CL signal generated by a H(2)O(2) -K(4) Fe(CN)(6) -fluorescein alkaline system enhanced by CdTe quantum dots. Under the optimized conditions, haemoglobin can be detected in concentration range 7.35 * 10(-9) -2.5 * 10(-6) mol/L, with a detection limit (3sigma) of 1.8 * 10(-9) mol/L and a relative standard deviation (RSD; for 5 * 10(-7) mol/L haemoglobin) of 2.06% (n = 11). The present CL method was successfully applied for the determination of haemoglobin in three kinds of blood samples taken from an infant, an adult man, an adult woman and two reference samples. Compared with previous reports, the CL method described in this work is simple and rapid, with high sensitivity. PMID- 22298438 TI - Erratum: Novel nanostructured scaffold for osteochondral regeneration: pilot study in horses. PMID- 22298439 TI - Polarization-induced charge distribution at homogeneous zincblende/wurtzite heterostructural junctions in ZnSe nanobelts. AB - Homogeneous heterostructural wurtzite (WZ)/zincblende (ZB) junctions are successfully fabricated in ZnSe nanobelts. Polarity continuity across the ZB/WZ interface is demonstrated. The saw-tooth-like potential profile induced by spontaneous polarization across the WZ/ZB/WZ interfaces is identified directly at the nanoscale. The polarization-induced charge distribution across the homogeneous heterostructural interfaces is proposed as a viable alternative approach towards charge tailoring in semiconductor nanostructures. PMID- 22298440 TI - Cyanation of aryl bromides with K4[Fe(CN)6] catalyzed by dichloro[bis{1 (dicyclohexylphosphanyl)piperidine}]palladium, a molecular source of nanoparticles, and the reactions involved in the catalyst-deactivation processes. AB - Dichloro[bis{1-(dicyclohexylphosphanyl)piperidine}]palladium [(P{(NC(5)H(10))(C(6)H(11))(2)})(2)PdCl(2)] (1) is a highly active and generally applicable C-C cross-coupling catalyst. Apart from its high catalytic activity in Suzuki, Heck, and Negishi reactions, compound 1 also efficiently converted various electronically activated, nonactivated, and deactivated aryl bromides, which may contain fluoride atoms, trifluoromethane groups, nitriles, acetals, ketones, aldehydes, ethers, esters, amides, as well as heterocyclic aryl bromides, such as pyridines and their derivatives, or thiophenes into their respective aromatic nitriles with K(4)[Fe(CN)(6)] as a cyanating agent within 24 h in NMP at 140 degrees C in the presence of only 0.05 mol % catalyst. Catalyst deactivation processes showed that excess cyanide efficiently affected the molecular mechanisms as well as inhibited the catalysis when nanoparticles were involved, owing to the formation of inactive cyanide complexes, such as [Pd(CN)(4)](2-), [(CN)(3)Pd(H)](2-), and [(CN)(3)Pd(Ar)](2-). Thus, the choice of cyanating agent is crucial for the success of the reaction because there is a sharp balance between the rate of cyanide production, efficient product formation, and catalyst poisoning. For example, whereas no product formation was obtained when cyanation reactions were examined with Zn(CN)(2) as the cyanating agent, aromatic nitriles were smoothly formed when hexacyanoferrate(II) was used instead. The reason for this striking difference in reactivity was due to the higher stability of hexacyanoferrate(II), which led to a lower rate of cyanide production, and hence, prevented catalyst-deactivation processes. This pathway was confirmed by the colorimetric detection of cyanides: whereas the conversion of beta-solvato-alpha-cyanocobyrinic acid heptamethyl ester into dicyanocobyrinic acid heptamethyl ester indicated that the cyanide production of Zn(CN)(2) proceeded at 25 degrees C in NMP, reaction temperatures of >100 degrees C were required for cyanide production with K(4)[Fe(CN)(6)]. Mechanistic investigations demonstrate that palladium nanoparticles were the catalytically active form of compound 1. PMID- 22298441 TI - Luminescent and light refractive polymers: synthesis and optical and photonic properties of poly(arylene ethynylene)s carrying silole and tetraphenylethene luminogenic units. AB - A facile route for the synthesis of luminescent and light refractive polymers is proposed. Silole-containing diyne and halogenated tetraphenylethene derivatives are synthesized and their coupling reactions furnish poly(arylene ethynylene)s with high molecular weights in high yields. All of the polymers are soluble and film-forming and possess a high thermal stability. They emit strong green lights when their solutions and nanoparticle suspensions are photoexcited. The polymers show high refractive indices with low chromatic dispersions. Their RI values can be modulated and their thin films can be crosslinked using UV irradiation, generating negative photoresist patterns. PMID- 22298442 TI - Transport into metal-organic frameworks from solution is not purely diffusive. AB - Chemistry in motion: a combination of confocal microscopy and reaction-diffusion modeling provided a powerful toolkit with which solution transport into metal organic framework crystals was studied. Commonly used pure diffusion models are insufficient to describe this process and, instead, it is necessary to account for the interactions of the guest molecules and the MOF scaffold. PMID- 22298443 TI - A ratiometric fluorescent probe for bisulphite anion, employing intramolecular charge transfer. AB - 4-(1H-benzimidazol-2-yl)benzaldehyde (1) has been developed as a new ratiometric fluorescent probe for bisulphite, based on the modulation of intramolecular charge transfer (ICT). Upon mixing with bisulphite in aqueous ethanol, an aldehyde-bisulphite adduct was formed and the ICT of the probe was switched off, which resulted in a ratiometric fluorescence response with an enhancement of the ratios of emission intensities at 368 and 498 nm. The detection range of the probe for bisulphite is in the 2.0-200 umol/L concentration range and the detection limit is 0.4 umol/L. Probe 1 produces a ratiometric fluorescent response to bisulphite with a marked emission wavelength shift (130 nm) and displays high selectivity for bisulphite over other anions. PMID- 22298444 TI - Clinical efficacy of macrophage-activating Chinese mixed herbs (MACH) in improvement of embryo qualities in women with long-term infertility of unknown etiology. AB - Despite the recent technological advances in in vitro fertilization and embryo transfer (IVF-ET), a significant proportion of women still do not become pregnant after long-term infertility, whether it is originally due to older age or other undetermined factors. In the present study, macrophage activating Chinese herbs (MACH) were evaluated for their effects on embryo qualities in women who were undergoing repeated IVF-ET because of long-term infertility. Thirty women, who had significantly low rates of developing good quality cleaved embryos and did not become pregnant after three or more cycles of Assisted Reproductive Technology (ART) procedure, were included in the study. Oral administration of MACH significantly increased the percentage of good quality early stage blastocysts (the number of grade 1 or grade 2 cleaved embryos/the number of retrieved oocytes) from 18.7 +/- 16.2% to 36.1 +/- 27.1% (1.9-fold increase, p < 0.01). The rate of good quality early stage blastocysts increased in all patients. In 19 patients who desired embryo transfer using late stage blastocysts, MACH significantly increased the percentage of late stage blastocysts from the initial value of 14.8 +/- 11.2% to 21.1 +/- 23.1% (1.4-fold increase, p < 0.05). The rate of embryonic progress into late stage blastocyst increased in 52.6% (10/19) of the patients. Furthermore, treatment with MACH significantly decreased the plasma follicle stimulating hormone (FSH) concentration on the day of oocyte retrieval from 14.4 +/- 3.2 to 10.5 +/- 2.4 mIU/ml (p < 0.05). No adverse events were observed with MACH supplementation, and there was no patient dropout. Administration of MACH resulted in improved embryo quality in the difficult cases. The present study demonstrates a new benefit of this herbal blend in women with refractory infertility of unknown etiology. PMID- 22298445 TI - Clinical outcomes of traditional Chinese medicine compound formula in treating sleep-disordered breathing patients. AB - Sleep-disordered breathing (SDB) is a prevalent affliction, which can range from simple snoring to severely obstructive sleep apnea. Compared to current treatment options of SDB, traditional Chinese medicine (TCM) provides a noninvasive way to relieve SDB-related symptoms and deaths. The purpose of this retrospective study was to observe the progression of adult SDB patients who had taken compound formula SZ + NUH (concentrated herbal granules) for four weeks. Depending on subjects' individual needs, minor additions of formulas or single herbs were allowed. We found a significant amount of relief from snoring among the 118 enrolled subjects, according to before-after scores observed through the Snore Outcome Survey (SOS). Furthermore, as projected from the moderate linear correlation in before-after scores, we inferred that those cases with more severe snoring at baseline had greater improvement after treatment. Excessive daytime sleepiness was also significantly improved according to the results of the Epworth Sleepiness Scale (ESS). Assessment, using the SF-36 (Taiwanese version) revealed possible benefits of SZ + NUH in improving multiple facets of subjects' quality of life. During treatment, no significant side effects occurred. In conclusion, the TCM compound formula based on SZ + NUH could be a safe and effective option for SDB treatment. PMID- 22298446 TI - Meta-analysis of the clinical effect of ligustrazine on diabetic nephropathy. AB - Ligustrazine, a bioactive component contained in Chuanxiong (Ligusticum chuanxiong Hort), is widely applied in the treatment of vascular diseases in China, e.g. myocardial and cerebral infarction. The aim of this study was to perform a meta-analysis of randomized controlled trials (RCTs) to evaluate the clinical effect of Ligustrazine on diabetic nephropathy (DN). PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Biological Medicine Database (CBM), China National Knowledge Infrastructure (CNKI) Database, etc. were searched by computer and manual methods to identify RCTs that were used to evaluate the clinical effect of Ligustrazine on DN patients. Twenty five studies comprising 25 RCTs were involved including 1645 patients (858 in the treatment group and 787 in the control group). The meta-analysis suggests that compared with the control group, Ligustrazine injection has a significant therapeutic effect on improving renal function (blood urea nitrogen [BUN] and serum creatinine [SCr]) and reducing in urine protein (24 h urine protein, urine micro albumin and urinary albumin excretion rate [UAER]) in DN patients. PMID- 22298447 TI - Diagnosis, treatment and prevention of autism via meridian theory. AB - A twelve-week pilot study was conducted on 11 male children, aged five to 19 years, who had ASD (autistic symptom disorder) of varying degrees of severity. These eleven subjects were each examined three times in the 12-week period: at the first week, 6th week, and 12th week. During each examination, two sets of full-body thermographs were taken of each child, before and fifteen minutes after drinking a solution of stable water clusters with a double helix configuration. This solution of stable water clusters is called double helix water (DHW). In the before thermographs, a consistent thermal pattern of six hot regions of body surface temperature were identified. They are: left and right upper forehead region of the face; left and right area in front of the center of the ear; left and right area of the inner extreme point of the eye; left and right collarbone region; left and right side neck region; and left and right armpit region. These areas may be interpreted as regions surrounding various acupoints along the GB, BL, ST, SI, SJ meridians. These meridians are yang meridians that on one end reach the head, and hence have branches reaching into the brain, and on the other end reach to the gastrointestinal tract and urinary bladder system. Thus, they can be considered to explain the major clinical symptoms of ASD. These thermal patterns, if confirmed in a larger clinical study, may lead to a new way to diagnose ASD, and to test the effectiveness of any treatment. When such a thermal pattern is discovered early, say around the age of 18 months, preventive action can be initiated before observation of any behavior disorder. We simultaneously studied the healing effect of stable water clusters with double helix configuration (DHW) on these subjects. The quantitative reduction of maximum temperature at these six regions was calculated. A consistent reduction was noted and suggests a positive healing effect taking place within a very short time period (fifteen minutes), and lasting over a long time period (12 weeks). Quantitative evaluation by the parents over the 12-week period showed that eight out of 11 children had physiological and behavioral improvement. Our findings with these small numbers suggest a reliable method of early diagnosis/detection and also an effective treatment of ASD. We therefore conclude that a study of larger numbers of children with ASD should be conducted. PMID- 22298448 TI - Herb-drug interaction of 50 Chinese herbal medicines on CYP3A4 activity in vitro and in vivo. AB - The purpose of this study is to evaluate the effects of Chinese herbal medicines on the enzymatic activity of CYP3A4 and the possible metabolism-based herb-drug interactions in human liver microsomes and in rats. Fifty single-herbal preparations were screened for the activity of CYP3A4 using human liver microsomes for an in vitro probe reaction study. The enzymatic activity of CYP3A4 was estimated by determing the 6beta-hydroxytestosterone metabolized from testosterone performed on a liquid chromatography-tandem mass spectrometry (LC MS/MS). Huang Qin (Scutellaria baicalensis Geprgi), Mu Dan Pi (Paeonia suffruticosa Andr.), Ji Shiee Terng (Spatholobus suberectus Dunn.) and Huang Qi (Astragalus membranaceus [Fisch] Bge) have been demonstrated to have remarkable inhibiting effects on the metabolism of CYP3A4, whereas Xi Yi Hua (Magnolia biondii Pamp.) exhibited a moderate inhibition. These five single herbs were further investigated in an animal study using midazolam. Mu Dan Pi, Ji Shiee Terng and Huang Qi were observed to have greatly increased in the C(max) and AUC of midazolam. This study provides evidence of possible herb-drug interactions involved with certain single herbs. PMID- 22298449 TI - 2 Hz electro-acupuncture at yinlingquan (SP9) and ququan (LR8) acupoints induces changes in blood flow in the liver and spleen. AB - According to the principles of traditional Chinese medicine, channels and collaterals within the body provide pathways through which qi and blood travel, and each channel or collateral is linked with a specific organ. The Yinlingquan (spleen 9, SP9) and Ququan (liver 8, LR8) acupoints represent the sea points of the spleen and liver meridians, respectively, from which qi and blood flow into their specific visceral organs. The purpose of this study was to investigate the changes in blood flow/perfusion in the liver and spleen resulting from the application of 2 Hz electro-acupuncture (EA) to the Yinlingquan (SP9) or Ququan (LR8) acupoints. A total of 18 Spragrue-Dawley rats were randomly divided into three groups of six rats each as follows: sham group receiving sham EA; Yinlingquan (SP9) group receiving 2 Hz EA, applied at bilateral Yinlingquan (SP9) acupoints; and Ququan (LR8) groups receiving 2 Hz EA, applied at bilateral Ququan (LR8) acupoints. The mean blood flow/perfusion of the spleen and liver was recorded using a laser Doppler blood flow monitor prior to EA (representing the baseline), during EA, and post-EA. Each measurement period lasted ten minutes. Nitric oxide levels were also measured from the right femoral arterial blood, following the conclusion of each series of blood flow/perfusion recordings. The results indicate that the sham EA did not increase the mean blood flow/perfusion in the liver or spleen; 2 Hz EA at bilateral Yinlingquan (SP9) acupoints increased the mean blood flow/perfusion in the spleen, but not in the liver. In contrast, 2 Hz EA at bilateral Ququan (LR8) acupoints increased the mean blood flow/perfusion in the liver, but not in the spleen. Nitric oxide levels showed no significant difference between any of the groups at any stage of the measurements. According to the results, we conclude that EA at the Yinlingquan (SP9) and Ququan (LR8) acupoints can increase the blood flow in the spleen and liver, respectively. PMID- 22298450 TI - Scutellaria baicalensis attenuates blood-brain barrier disruption after intracerebral hemorrhage in rats. AB - Disruption of the blood-brain barrier (BBB) contributes to the inflammatory response and edema formation in the brain, exacerbating brain damage. The present study evaluated the effects of Scutellaria baicalensis (SR) water extracts on BBB disruption after intracerebral hemorrhage (ICH) in rats. ICH was induced by stereotaxic intrastriatal injection of bacterial type VII collagenase, and SR was administrated orally three times (50 mg/ml/kg) during the 48 h after ICH onset. SR treatment significantly reduced the degree of (1) hemorrhage volume and edema percentage of the ipsilateral hemisphere, (2) brain water content, (3) MPO positive neutrophil infiltration in the peri-hematoma, and (4) BBB permeability measured by Evans blue leakage. In addition, expression of matrix metalloproteinase (MMP)-9, MMP-12, and tissue inhibitor of MMPs (TIMP)-1 were investigated with immunohistochemistry. SR treatment reduced MMP-9 and MMP-12 expression in the peri-hematoma after ICH. These results indicate that SR attenuates the BBB disruption through anti-inflammatory effects and suppression of MMP expression. These findings provide a pharmacological basis for the use of SR in the treatment of the BBB disruption following stroke and trauma. PMID- 22298451 TI - Antioxidant and anti-inflammatory effects of a hypoglycemic fraction from Cucurbita ficifolia Bouche in streptozotocin-induced diabetes mice. AB - Type 2 diabetes is characterized by oxidative stress and a chronic low-grade inflammatory state, which also play roles in the pathogenesis of this disease and the accompanying vascular complications by increasing the production of free radicals and pro-inflammatory cytokines. Cucurbita ficifolia Bouche (C. ficifolia) is an edible Mexican plant whose hypoglycemic activity has been demonstrated in several experimental and clinical conditions. Recently, D-chiro inositol has been proposed as the compound responsible for the hypoglycemic effects; however, the antioxidant and anti-inflammatory potential of this plant has not yet been explored. The aim of this research is to study the influence of a hypoglycemic, D-chiro-inositol-containing fraction from the C. ficifolia fruit (AP-Fraction) on biomarkers of oxidative stress, as well as on the inflammatory cytokines in streptozotocin-induced diabetes. The AP-Fraction obtained from the mature fruit of C. ficifolia contained 3.31 mg of D-chiro-inositol/g of AP Fraction. The AP-Fraction was administrated daily by gavage to normal mice for 15 days as a preventive treatment. Then these animals were given streptozotocin, and the treatments were continued for an additional 33 days. Pioglitazone was used as a hypoglycemic drug for comparison. Administration of the AP-Fraction significantly increased glutathione (GSH) and decreased malondialdehyde (MDA) in the liver without significantly affecting the levels in other tissues. The AP Fraction reduced TNF-alpha and increased IL-6 and IFN-gamma in serum. Interestingly, the AP-Fraction also increased IL-10, an anti-inflammatory cytokine. These results suggest that C. ficifolia might be used as an alternative medication for the control of diabetes mellitus and that it has antioxidant and anti-inflammatory properties in addition to its hypoglycemic activity. PMID- 22298452 TI - Anti-fatigue effect of Zizania caudiflora (Turczaninow) Nakai. AB - The purpose of the present study was to investigate the anti-fatigue effect of Zizania caudiflora (Turczaninow) Nakai (ZC) and hydrolyzed ZC by malted barley (HZC) through a forced swimming test (FST) in mice. After the first measurement of immobility times, the mice were divided into control, fluoxetine, ZC, and HZC groups to match the swimming times in each group. The immobility times in the FST of the control as well as the fluoxetine, ZC, and HZC-administered groups after administration for three days were 135.3 +/- 3.3,66.8 +/- 3.9,120.2 +/- 2.7, and 123.2 +/- 2.9 sec, respectively. The immobility times in the FST of the ZC and HZC-administered groups for 14 days were significantly decreased in comparison with the control group (p < 0.01). In addition, the immobility times of ZC and HZC-administered groups for 14 days in the tail-suspension test were also significantly decreased in comparison with the control group (p < 0.05). The plasma levels of albumin, glucose, and total protein were significantly increased and creatine phosphokinase was significantly decreased in the ZC and HZC administered groups compared to the control group. However, the levels of lactate dehydrogenase and blood urea nitrogen in the ZC and HZC-administered groups did not represent a significant difference compared to the control group. In summary, these results suggest that ZC or HZC might be a candidate for an anti-fatigue agent. PMID- 22298453 TI - An improved acute gouty arthritis rat model and therapeutic effect of rhizoma Dioscoreae nipponicae on acute gouty arthritis based on the protein-chip methods. AB - Rhizoma Dioscoreae nipponicae (RDN) is an herbal medicine. In the theories of Traditional Chinese Medicine (TCM), the function of RDN is to expel wind and remove dampness. Inflammatory mechanisms play an important role in the pathological process and prognosis of acute gouty arthritis (AGA). The aim of this study was to determine the specially expressed proteins through testing the proteins of the synovium in rats with AGA. The animal model of AGA was set up by Monosodium urate crystal (MSU) combined with hypoxanthine (HX), which was ameliorated in our previous experiment. Blood samples for measurement of serum uric acid were collected prior to sacrifice. Outcomes were assessed (two days after injection) by histological stain and protein quantitation. Three chips of RayBio(r) Human Label-based Antibody Array I were applied to detect 90 proteins in the synovium tissue of AGA rats. 14 differently expressed proteins were found in the synovium of AGA rats, and nine of them were first found in this model. There were seven up-regulated and seven down-regulated proteins, both TRAIL and Neuropilin-2 could be identified as key contributors to the pathomechanism of AGA. PMID- 22298454 TI - Eucommiae cortex inhibits TNF-alpha and IL-6 through the suppression of caspase-1 in lipopolysaccharide-stimulated mouse peritoneal macrophages. AB - Eucommiae cortex (EC) is used in various traditional Korean medicines in the form of tonics, analgesics, and sedatives. However, the underlying mechanism of its anti-inflammatory effect remains unclear. This study attempts to determine the effects of EC on lipopolysaccharide (LPS)-induced inflammatory responses in mouse peritoneal macrophages. The findings of the study show that EC inhibits the LPS induced production of tumor necrosis factor-alpha and interleukin-6. Exposure to EC also reduces an inflammation-induced increase in the levels of cyclooxigenase 2 and the production of prostaglandin E(2) and nitric oxide in mouse peritoneal macrophages. Furthermore, EC suppresses the activation of nuclear factor-kappa B and caspase-1. These results provide novel insights into the pharmacological action of EC and indicate that EC has a potential in the treatment of inflammatory diseases. PMID- 22298455 TI - Cimicifuga foetida L. inhibited human respiratory syncytial virus in HEp-2 and A549 cell lines. AB - Human respiratory syncytial virus (HRSV) causes serious pediatric infection of the lower respiratory tract without effective therapeutic modality. Sheng-Ma-Ge Gen-Tang (SMGGT; Shoma-kakkon-to) has been proven to be effective at inhibiting HRSV-induced plaque formation, and Cimicifuga foetida is the major constituent of SMGGT. We tested the hypothesis that C. foetida effectively inhibited the cytopathic effects of HRSV by a plaque reduction assay in both human upper (HEp2) and lower (A549) respiratory tract cell lines. Its ability to stimulate anti viral cytokines was evaluated by an enzyme-linked immunosorbent assay (ELISA). C. foetida dose-dependently inhibited HRSV-induced plaque formation (p < 0.0001) before and after viral inoculation, especially in A549 cells (p < 0.0001). C. foetida dose-dependently inhibited viral attachment (p < 0.0001) and could increase heparins effect on viral attachment. In addition, C. foetida time dependently and dose-dependently (p < 0.0001) inhibited HRSV internalization. C. foetida could stimulate epithelial cells to secrete IFN-beta to counteract viral infection. However, C. foetida did not stimulate TNF-alpha secretion. Therefore, C. foetida could be useful in managing HRSV infection. This is the first evidence to support that C. foetida possesses antiviral activity. PMID- 22298456 TI - Mulberry leaf extract stimulates glucose uptake and GLUT4 translocation in rat adipocytes. AB - Mulberry (Morus alba L.) leaf tea is promoted for its health benefits and the control of diabetes in Asian nations. The blood glucose lowering activity of mulberry leaf extract (MA) has been proven; however, the molecular basis underlying this effect remains unclear. The aim of the present work is to elucidate its mechanism of the antihyperglycemic action, by examining the effect of MA on glucose uptake and the translocation of glucose transporter 4 protein (GLUT4) to the plasma membrane of adipocytes isolated from diabetic rats. The incubation of adipocytes with 5-45 MUg/ml MA resulted in 31-54% increase of glucose uptake in a dose-dependent manner. This glucose uptake enhancing effect was inhibited by the phosphoinositol 3-kinase (PI3-K) inhibitor, wortmannin (100 nM). The GLUT4 protein on the plasma membrane fraction of adipocytes was markedly increased after treatment with 15 MUg/ml MA extract. Interestingly, gallic acid, one of the phenolic compounds found in MA extract, increased glucose uptake and enhanced the translocation of GLUT4 at concentrations comparable to the amount of gallic acid in the effective concentration ranges of MA. Thus, it is likely that gallic acid contributes, at least in part, to its antihyperglycemic activity. The present results suggest that the antihyperglycemic action of MA is mediated by increasing glucose uptake via the activation of PI3-K signaling pathway and translocation of GLUT4 to the plasma membrane. These findings are the first molecular evidence supporting the mulberry tea as herbal medicine for diabetic patients. PMID- 22298457 TI - Dehydrocorydaline inhibits breast cancer cells proliferation by inducing apoptosis in MCF-7 cells. AB - Dehydrocorydaline is an alkaloid isolated from traditional Chinese herb Corydalis yanhusuo W.T. Wang. We discovered that it possessed anti-tumor potential during screening of anti-tumor natural products from Chinese medicine. In this study, its anti-tumor potential was investigated with breast cancer line cells MCF-7 in vitro. The anti-proliferative effect of dehydrocorydaline was determined by MTT assay and the mitochondrial membrane potential (Delta Psi m) was monitored by JC 1 staining. DNA fragments were visualized by Hoechst 33342 staining and DNA ladder assay. Apoptotic related protein expressions were measured by Western blotting. Dehydrocorydaline significantly inhibited MCF-7 cell proliferation in a dose- dependent manner, which could be reversed by a caspase-8 inhibitor, Z-IETD FMK. Dehydrocorydaline increased DNA fragments without affecting DeltaPsim. Western blotting assay showed that dehydrocorydaline dose-dependently increased Bax protein expression and decreased Bcl-2 protein expression. Furthermore, dehydrocorydaline induced activation of caspase-7,-8 and the cleavage of PARP without affecting caspase-9. These results showed that dehydrocorydaline inhibits MCF-7 cell proliferation by inducing apoptosis mediated by regulating Bax/Bcl-2, activating caspases as well as cleaving PARP. PMID- 22298458 TI - Mountain ginseng extract exhibits anti-lung cancer activity by inhibiting the nuclear translocation of NF-kappaB. AB - Administration of mountain ginseng (MG) extract can restore advanced cancer to a normal state. To elucidate the mechanism by which MG extract prevents the progression of lung cancer, the processes of proliferation and death of lung cancer cells (A549) were examined after treatment with MG extract. Butanol extracted MG (BX-MG) showed a high inhibitory effect (IC(50) = 2 mg/ml) by attenuating proliferation and inducing apoptosis in lung cancer cells. By HPLC-UV analysis of BX-MG, ginsenosides, Rb1 was identified as the most abundant ginsenoside, followed by Rg1, Re, Rc and Rb2. BX-MG induced caspase-3 dependent apoptosis by inhibiting NF-kappaB. In addition, BX-MG activated p53 and p21, resulting in the attenuated proliferation of A549 cells. Reduced activity of the NF-kappaB promoter and increased activity of the p53 promoter indicate that BX-MG regulates apoptosis at the level of transcription in lung cancer cells. Furthermore, BX-MG blocked the nuclear translocation of RelA and the associated reduction in surviving. These results suggest that BX-MG inhibits lung cancer cell growth by activating tumor suppressors and inhibiting nuclear translocation of NF-kappaB. PMID- 22298459 TI - Comparative root protein profiles of Korean ginseng (Panax ginseng) and Indian ginseng (Withania somnifera). AB - Ginsenosides and withanolides are the secondary metabolites from Panax ginseng and Withania somnifera, respectively. These compounds have similar biological properties. Two-dimensional electrophoresis (2-DE) analysis was utilized to reveal the protein profile in the roots of both plants, with the aim of clarifying similarly- and differentially-expressed proteins. Total proteins of Korea ginseng (P. ginseng) and Indian ginseng (W. somnifera) roots were separated by 2-DE using a pH 4-7 immobilized pH gradient strip in the first dimension and 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis in the second dimension. The protein spots were visualized by silver staining. Twenty-one P. ginseng proteins and 35 W. somnifera proteins were chosen for identification by matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry; of these, functions were ascribed to 14 and 22 of the P. ginseng and W. somnifera proteins, respectively. Functions mainly included general cell metabolism, defense and secondary metabolism. ATPase and alcohol dehydrogenase proteins were expressed in both plants. The results of this study, to our knowledge, are the first to provide a reference 2-DE map for the W. somnifera root proteome, and will aid in the understanding of the expression and functions of proteins in the roots of Korean ginseng and Indian ginseng. PMID- 22298460 TI - Controlled collagen crosslinking process in tissue-engineered fibroblast sheets for preventing scar contracture on the surface of lungs. AB - For preventing the scar contracture of host tissue and adjusting the tensile strength of covering cell sheets, a controlled collagen crosslinking step process in the preparation of skin-fibroblast sheets for repairing wound was investigated by using beta-aminopropionitrile (BAPN), a collagen crosslinking inhibitor, in the culture medium. Skin fibroblasts obtained from neonatal rats were cultured in medium with and without 0.25 mm BAPN for 7 days and seeded on temperature responsive culture dishes. After the confluent cells were non-invasively harvested as a monolithic cell sheet, two cell sheets were transplanted to a lung injury site of athymic rats, which was closed by neither fibrin glue nor suturing. Four weeks after the transplantation the animals were sacrificed and the lungs with the transplanted cell sheets were examined. Although the control cell sheet-transplanted lungs contracted the surrounding tissue, BAPN-treated cell sheet-transplanted lungs showed no contraction of the tissue. Collagen fibres of control cell sheets were more dense and thick than those of BAPN treated cell sheets, where the crosslinking of collagen fibres was clearly inhibited. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that BAPN-treated cell sheets gave no beta-chain band, indicating that the collagen crosslinkings of the fibroblast sheets were able to be controlled by BAPN. BAPN-treated fibroblast sheets promise to allow wound clefts to be repaired without scar contractures. PMID- 22298461 TI - Controlled ambipolar charge transport through a self-assembled gold nanoparticle monolayer. AB - An active mechanism for controlling ambipolar charge transport is developed based on self-assembled monolayers of gold nanoparticles. Electron and hole currents are manipulated by controlling the gate bias in order to overcome the intrinsic material limitations. The endurance and retention measurements confirm that this method exhibits good electrical reliability and stability. This solution process approach has potential for applications in large-area printed electronic devices. PMID- 22298462 TI - Nanoscale growth of molecular oxides: assembly of a {V6} double cubane between two lacunary {P2W15} polyoxometalates. PMID- 22298463 TI - Lithol Red: a systematic structural study on salts of a sulfonated azo pigment. AB - The first systematic series of single-crystal diffraction structures of azo lake pigments is presented (Lithol Red with cations=Mg(II), Ca(II), Sr(II), Ba(II), Na(I) and Cd(II)) and includes the only known structures of non-Ca examples of these pigments. It is shown that these commercially and culturally important species show structural behaviour that can be predicted from a database of structures of related sulfonated azo dyes, a database that was specifically constructed for this purpose. Examples of the successful structural predictions from the prior understanding of the model compounds are that 1) the Mg salt is a solvent-separated ion pair, whereas the heavier alkaline-earth elements Ca, Sr and Ba form contact ion pairs, namely, low-dimensional coordination complexes; 2) all of the Lithol Red anions exist as the hydrazone tautomer and have planar geometries; and 3) the commonly observed packing mode of alternating inorganic layers and organic bilayers is as expected for an ortho-sulfonated azo species with a planar anion geometry. However, the literature database of dye structures has no predictive use for organic solvate structures, such as that of the observed Na Lithol Red DMF solvate. Interestingly, the Cd salt is isostructural with the Mg salt and not with the Ca salt. It is also observed that linked eight membered [MOSO](2) rings are the basic coordination motif for all of the known structures of Ca, Sr and Ba salts of sulfonated azo pigments in which competing carboxylate groups are absent. PMID- 22298464 TI - Divergent synthesis of ruthenium alkynyl dendrimers and a two-photon absorption cross-section dendritic effect. AB - Ruthenium alkynyl dendrimers up to second generation in size have been prepared by a divergent route and exploiting Sonogashira coupling. The cubic NLO properties have been examined by wide spectral range fs Z-scan studies, revealing an NLO dendritic effect. The significant increase in NLO properties seen on generation increase is maintained when the coefficients are scaled by the number of metal atoms, the dendrimer molecular weights, or the number of "effective" (delocalizable pi) electrons in the dendritic structures. PMID- 22298465 TI - Early viral load and recipient interleukin-28B rs12979860 genotype are predictors of the progression of hepatitis C after liver transplantation. AB - There have been few detailed studies of viral kinetics after liver transplantation (LT), and conflicting data have been reported on viral loads and the severity of recurrent hepatitis C virus (HCV) disease. This long-term study aimed to examine (1) the impact of HCV RNA levels at specific points in time within the first year and (2) the influence of interleukin-28B (IL-28B) genotypes on patient outcomes and the severity of recurrent HCV disease. The viral loads were measured 2, 4, 12, 24, and 48 weeks after LT, and the recipient/donor IL-28B genotypes of 164 patients were determined. A Cox regression analysis showed that the viral load at week 2 was an independent negative predictor of recipient outcomes. A week 2 viral load >= 6.0 log(10) IU/mL was significantly associated with reduced patient survival. After a mean follow-up of 6.5 years, 21 of 164 patients (12.8%) developed a cholestatic type of HCV recurrence and/or rapidly progressed to cirrhosis within 1 year. A multivariate binary regression analysis showed that HCV viremia at week 2 and a non-C/C recipient IL-28B genotype were independent risk factors for cholestatic recurrent HCV. No predictive factors could be found for the occurrence of recurrent liver cirrhosis 5 and 10 years after LT. Our study shows that the HCV RNA level at week 2 and the recipient IL 28B genotype are independent, statistically significant risk factors for post-LT cholestatic HCV, and it emphasizes the importance of viral load monitoring and IL 28B genotyping for identifying HCV recipients at risk for severe HCV recurrence. PMID- 22298466 TI - Shape-dependent acidity and photocatalytic activity of Nb2O5 nanocrystals with an active TT (001) surface. AB - Nb(2)O(5) nanorods and nanospheres were synthesized, and their photocatalytic activity for methylene blue decomposition in water compared. Nb(2)O(5) nanorods clearly displayed higher activity, despite their comparable surface area. With a shape-dependent surface acidity, hydrothermal stability, and high photoactivity, these Nb(2)O(5) nanorods are a unique and exciting nanomaterial for non-classical photocatalytic mineralization of organic compounds in water. PMID- 22298467 TI - Hormone receptor and human epidermal growth factor receptor 2 status evaluation on ThinPrep specimens from breast carcinoma: correlation with histologic sections determination. AB - BACKGROUND: Fine-needle aspiration cytology (FNAC) is a well-accepted procedure for the diagnosis and biological characterization of breast carcinoma. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status have a strong prognostic and predictive value in invasive breast carcinoma (IBC). ThinPrep (TP) cytology, which uses an alcohol based fixative, is increasingly being used for immunocytochemistry. In this study, the authors compared the immunocytochemical evaluation of hormone receptors (HR) and HER2 on TP-processed FNAC with the immunohistochemical analysis performed on the corresponding formalin-fixed paraffin-embedded (FFPE) breast tumor specimens, which are considered the gold standard. METHODS: FNACs were performed on 116 primary IBCs at the time of diagnosis and subjected to immunocytochemical evaluation of HR and HER2 using the TP method. The same markers were immunohistochemical evaluated on the corresponding FFPE tissue specimens. HER2 fluorescent in situ hybridization analysis was performed only on the equivocal immunohistochemical results. RESULTS: The HR results of the TP cytology specimens showed a very good agreement with those of the corresponding FFPE tissue samples (Cohen kappa test = 0.92; concordance rate = 98%) for estrogen receptor, and a good agreement (kappa = 0.76; concordance rate = 90.9%) for progesterone receptor. A perfect agreement (kappa = 1) was observed between TP and FFPE tissue samples in evaluating HER2 status. CONCLUSIONS: Alcohol-based fixation seems not to affect the immunocytochemical evaluation of HR and HER2. Considering the high levels of agreement between the evaluation of HR and HER2, on both cytology specimens and on the corresponding FFPE tissue samples, the authors concluded that the TP technique can be routinely used for the biological characterization of IBC. PMID- 22298469 TI - Sinusoidal C4d deposits in liver allografts indicate an antibody-mediated response: diagnostic considerations in the evaluation of liver allografts. AB - There is a paucity of data concerning the correlation of complement component 4d (C4d) staining in liver allografts and antibody-mediated rejection. Data about the location and character of C4d deposits in native and allograft liver tissues are inconsistent. We performed C4d immunofluorescence (IF) on 141 fresh-frozen liver allograft biopsy samples and native livers, documented the pattern of C4d IF staining, and correlated the findings with the presence of donor-specific alloantibodies (DSAs). A linear/granular sinusoidal pattern of C4d IF was noted in 18 of 28 biopsy samples obtained after transplantation from patients with positive crossmatch and detectable donor-specific alloantibody (pos-XM/DSA) findings. None of the 59 tested biopsy samples from patients with negative crossmatch and detectable donor-specific alloantibody (neg-XM/DSA) findings were C4d-positive (P < 0.001). No significant association was found between pos-XM/DSA and C4d IF staining in other nonsinusoidal liver compartments. To compare the results of sinusoidal C4d staining with IF and 2 immunohistochemistry (IHC) techniques, C4d IHC was performed on 19 liver allograft biopsy samples in which a sinusoidal pattern of C4d IF had been noted. Sinusoidal C4d IHC findings were negative for 17 of the 19 biopsy samples; 2 showed weak and focal staining, and both patients had pos-XM/DSA findings. Portal vein endothelium staining was present in only 1 IF-stained biopsy sample (pos-XM/DSA) but in 11 IHC-stained biopsy samples (2 of the 11 samples had neg-XM/DSA findings). We conclude that sinusoidal C4d deposits detected by IF in frozen tissue samples from liver allograft recipients correlate with the presence of DSAs and an antibody-mediated alloresponse. These observations are similar to findings reported for other solid organ transplants and can provide relevant information for patient management. Further validation of IHC techniques for C4d detection in liver allograft tissue is required. PMID- 22298470 TI - Solid-state NMR spectroscopy on cellular preparations enhanced by dynamic nuclear polarization. PMID- 22298471 TI - Gold-catalysed oxyarylation of styrenes and mono- and gem-disubstituted olefins facilitated by an iodine(III) oxidant. AB - 1-Hydroxy-1,2-benziodoxol-3(1H)-one (IBA) is an efficient terminal oxidant for gold-catalysed, three-component oxyarylation reactions. The use of this iodine(III) reagent expands the scope of oxyarylation to include styrenes and gem disubstituted olefins, substrates that are incompatible with the previously reported Selectfluor-based methodology. Diverse arylsilane coupling partners can be employed, and in benzotrifluoride, homocoupling is substantially reduced. In addition, the IBA-derived co-products can be recovered and recycled. PMID- 22298472 TI - Arginase-1: a novel immunohistochemical marker of hepatocellular differentiation in fine needle aspiration cytology. AB - BACKGROUND: Arginase-I is a key urea cycle metalloenzyme that has been used as an immunohistochemistry (IHC) marker for hepatocellular carcinoma (HCC). Previous studies have demonstrated the efficacy of HepPar-1 and glypican-3 (GPC-3) IHC in liver fine needle aspiration (FNA) cytology. METHODS: Arginase-1 IHC was performed on FNA cell blocks, and its performance characteristics were compared with HepPar-1 and GPC-3. Ninety-two formalin-fixed, paraffin-embedded cell blocks were selected (HCC [n = 44], cirrhosis [n = 2], focal nodular hyperplasia [n = 3], hepatic adenomas [n = 2], dysplastic nodules [n = 6], and metastatic carcinomas [n = 35]). IHC staining with antibodies directed against arginase-1, HepPar-1, and GPC-3 was performed with appropriate positive and negative controls. RESULTS: Arginase-1 positivity was demonstrated in 37 of 44 (84.1%) cases of HCC, compared with 32 of 44 cases (72.7%) and 25 of 44 cases (56.8%) for HepPar-1 and GPC-3, respectively. Arginase-1 and GPC-3 expression were not observed in any cases of metastatic carcinoma (0%), whereas HepPar-1 expression was present in 1 case of metastatic carcinoma. In addition, both arginase-1 and HepPar-1 expression were present in all 13 cases (100%) of nonmalignant hepatocellular lesions, whereas GPC-3 expression was absent in all 13 cases (0%). CONCLUSION: This study demonstrates that both arginase-1 and HepPar-1 are effective IHC markers of hepatocellular differentiation. Furthermore, arginase-1 demonstrates superior sensitivity compared with GPC-3 and HepPar-1 in the diagnosis of HCC, whereas GPC-3 demonstrates superior specificity, as staining is not observed in benign hepatocellular lesions. Hence, use of arginase-1 with HepPar-1 and GPC-3 can aid in the diagnosis of HCC and separating from metastatic carcinoma. PMID- 22298473 TI - Clonidine-induced changes in the spectral distribution of heart rate variability correlate with performance on a test of sustained attention. AB - Conventional measures of cardiovascular activity correlate poorly with psychological variables and therefore provide imperfect physiological indices of arousal. We have investigated the effects of clonidine upon the spectral distribution of heart rate variability and upon performance on a test of sustained attention. Our findings suggest that activity of the central noradrenergic system influences the distribution of heart rate variability in the ~ 0.1 Hz range. Furthermore, the finding of a strong correlation between the effects of clonidine upon each of these variables supports the use of spectral analysis of heart rate variability in the study of arousal. PMID- 22298474 TI - Effect of acute tryptophan depletion on mood and appetite in healthy female volunteers. AB - Twelve healthy female subjects received the following three drinks in a double blind, semi-balanced, cross over design: (a) 50 g of amino acids without L tryptophan (LTP); (b) 50 g of amino acid with LTP (balanced); (c) plain water. Compared to both the balanced amino acid mixture and plain water, the LTP drink significantly lowered plasma total and free tryptophan at 4.5 h. However, compared to the two control conditions, there was no effect of the LTP drink on subjective ratings of mood or hunger. Similarly, the LTP drink did not alter significantly either total calorie intake or the macronutrient content of a test meal 5 h after drink ingestion. PMID- 22298475 TI - Stimulation of central 5-HT1D receptors causes hypothermia in the guinea-pig. AB - The 5-HT(1) receptor agonist GR46611 (3-30 mg/kg s.c.) caused a dose-related decrease in rectal temperature in the adult guinea-pig. A lower dose (20 MUg) administered directly into the lateral cerebral ventricle also caused a hypothermic response, suggesting that this effect is centrally mediated. GR46611 induced (10 mg/kg s.c.) hypothermia was not attenuated by WAY100135 (3-10 mg/kg s.c.), ritanserin (0.3-1 mg/kg s.c.), spiperone (0.1-0.3 mg/kg s.c.) and ondansetron (0.1-1 mg/kg s.c.), suggesting that 5-HT(1A), 5-HT(2A), 5-HT( 2C) and 5-HT(3) receptors are unlikely to be involved in this response. In contrast, the poorly selective 5-HT receptor antagonist, metergoline (1-10 mg/kg s.c.), and the potent 5-HT(1D) receptor antagonist, GR127935 (0.1-1 mg/kg p.o.), antagonized the effects of GR46611. The present data suggest that antagonism of GR46611-induced hypothermia may be useful for assessing the potency and duration of action of centrally-acting 5-HT( 1D) receptor antagonists in the guinea-pig. PMID- 22298476 TI - Alcohol consumption and lifestyle in medical students. AB - 1st, 2nd, 3rd and 5th year medical students completed a questionnaire with 35 questions relating to diet, general health, exercise, smoking and drinking. Based on reported 'typical weekly intake' one-third of male non-Asian students in years 1-3, and 59% in year 5 were drinking above safe limits. 12-26% of non-Asian female students were drinking above safe limits. In all years most Asian students were drinking within safe limits. Non-Asians smoked more than Asians and males smoked more than females. A group of non-Asian male students with alcohol intake for the previous week > 35 units was compared with a group of safe drinkers (<25 > 0 units/week). Significantly more of the former group drank > 10 units per occasion, had been hurt as a result of someone's drinking, had caused physical harm and drank at lunch. Although 65% were aware their level of drinking was dangerous, only 7.5% wanted advice on safe drinking and only 5% wanted to drink less. The dangerous level drinkers ate less fruit and smoked more cigarettes than those drinking safely, but there were no other significant differences and there was no evidence for impaired academic performance. PMID- 22298477 TI - Complex of rapid movements and vocalization induced by RX336-M in mice: possible relevance to Tourette's syndrome. AB - RX336-M (7,8-dihydro-5',6'-dimethylcyclohex-5'-eno-1',2',8',14 codeinone) induced a complex of simultaneous rapid movements of body parts accompanied by a single squeak-vocalization, which occurred at irregular intervals, when injected i.p. in mice. The complex included whole body jerks and head-shakes and its frequency was dose dependent between 0.1 and 20 mg/kg. Frequency after a 5 mg/kg dose was reduced by haloperidol (0.5-10 mg/kg, i.p.), ritanserin (0.1-10 mg/kg, i.p.) and ICI 169,369 (2.0 mg/kg, i.p.), suggesting the possible involvement of 5-HT(2A) and/or dopamine receptors. The possible relevance of the behavioural effects of RX336-M to the tics and vocalization of Tourette's syndrome is discussed. PMID- 22298478 TI - The effect of Ro 15-4513, an inverse agonist at the benzodiazepine receptor, on the exploratory response to novelty in the playground maze. AB - The effects of chlordiazepoxide and the inverse agonist, Ro 15-4513, were compared on the exploratory response of rats to a novel object introduced into a familiar environment containing seven familiar objects. While chlordiazepoxide (5 mg/kg) increased the novelty response, Ro 15-4513 reduced the response in a dose dependent manner (0.5-5.0 mg/kg). This action was specific to novelty since the response to the familiar objects was unaffected. Both drugs produced some reduction in ambulation. The effects of both drugs were blocked by flumazenil (10 mg/kg), which at this dose did not itself have any intrinsic effect on the response. Muscimol (0.001 mg/kg) had a weak chlordiazepoxide-like effect and baclofen (3 mg/kg) had a weak effect in the opposite direction. PMID- 22298479 TI - The effects of chronic lithium chloride administration on some behavioural and immunological changes in the bilaterally olfactory bulbectomized rat. AB - The effect of chronic lithium chloride (3 mmol/kg for 15 days) on the 'open field' activity and some aspects of immune function was studied in bilaterally olfactory bulbectomized and sham-operated rats. Chronic lithium chloride administration did not reverse the hyperactivity of the bulbectomized rats in the 'open field', neither did it affect the growth rate significantly. Lithium chloride treatment reversed the deficit in the neutrophil phagocytic response and slightly reversed the deficit in lymphocyte proliferation induced by mitogens that resulted from bulbectomy. The reduction in neutrophil catalase activity, and the increase in superoxide dismutase activity, that occurred following bulbectomy was reversed by chronic lithium treatment. However, the reduction in the proportion of lymphocytes, and the increase in the proportion of neutrophils that occurred in the bulbectomized rats was not reversed significantly by chronic lithium treatment. Chronic lithium treatment reversed the deficit in noradrenaline in the amygdaloid cortex and hypothalamus of the bulbectomized rats and the reduction in the dopamine concentration in the amygdaloid cortex. No changes in the concentrations of 5-HT and 5-HIAA could be detected in any of the brain regions studied. Thus there is a disparity between the lack of effect of lithium chloride on 'open field' behaviour and its beneficial effects in correcting some of the immune and neurotransmitter deficits which were observed in the bulbectomized rats. PMID- 22298480 TI - The compliance with antidepressants in general practice. AB - It has been known for some time that the compliance with antidepressants in general practice is sub-optimal, but no new studies have been carried out since the 1970s, since which time training in general practice has improved and new classes of antidepressants have been introduced. In this study 46 patients commenced on an antidepressant for clinical reasons by their GP were interviewed 10-12 weeks later by a research worker. Thirty two percent of patients stopped medication within 6 weeks and 63% of these did not inform their GP of their decision. Side-effect burden was significantly associated with non-compliance. Selective serotonin re-uptake inhibitors showed a slight but non-significant compliance advantage in this small study but all patients treated with SSRIs were initially prescribed a dose for which there is evidence of superiority of effect over placebo, while only 30% of those on tricyclics were prescribed such a dose. Further work to establish accurate methods of determining compliance and effective ways of enhancing compliance with antidepressants in general practice is required. PMID- 22298481 TI - Cholinergic blockade and human information processing: are we asking the right questions? AB - This paper reviews the literature on the effect of cholinergic blockade on human information processing, within the context of current debate concerning the relationship between deficits in attention and memory tasks. It questions whether we are making the most of the tools available to us and the opportunities there are to explore not only the neurochemical correlates of psychological function, but also the cognitive models on which the psychopharmacological research feeds. Current theoretical issues within cognitive psychology are discussed, and the drug studies are re-evaluated in terms of the resource model of information processing, which focuses on issues of automaticity of processes, and resource availability, rather than modular dissociations between attention and memory. PMID- 22298482 TI - Psychiatric complications of 'Ecstasy' use. AB - Two case reports are presented of significant psychiatric disorders associated with ingestion of 'Ecstasy' (3,4-methylenedioxymethamphetamine), a recreational drug whose use appears to be increasing. In one case, the patient developed a brief paranoid psychosis which recurred and persisted for at least a month after he took a second dose of the drug. In the other, the patient experienced persistent symptoms of anxiety and depression for > 8 weeks after taking the drug. PMID- 22298483 TI - Is the beta-down-regulation a prerequisite of the antidepressant activity? PMID- 22298485 TI - New insights into classical issues in schizophrenia. PMID- 22298484 TI - Sigma ligands as potential psychotropic drugs. PMID- 22298486 TI - Dementia. PMID- 22298487 TI - New approaches to drug dependency. PMID- 22298488 TI - Depression in the elderly. PMID- 22298489 TI - Beyond the receptor: the significance of gene expression for psychopharmacology. PMID- 22298490 TI - Tuning the properties of ZnO, hematite, and Ag nanoparticles by adjusting the surface charge. AB - A poly (acryl acid) (PAA) post-treatment method is performed to modify the surface charge of ZnO nanospheres, hematite nanocubes, and Ag nanoprisms from highly positive to very negative by adjusting the PAA concentration, to and greatly modify their photoluminescence, cytotoxicity, magnetism, and surface plasmon resonance. This method provides a general way to tune the nanoparticle properties for broad physicochemical and biological applications. PMID- 22298491 TI - Measurement of pH values in human tissues by two-photon microscopy. AB - pH values go live! A ratiometric two-photon (TP) probe (NP1, see scheme) that has a significant TP action cross-section, high photostability, negligible toxicity, and can estimate pH values in live cells and human tissues by two-photon microscopy is described. NP1 can detect the difference in pH between live cells from the gastroesophageal junction (GEJ) and the lower esophageal sphincter of patients with and without esophagitis. PMID- 22298492 TI - Minimization of organocuprate complexity through self-organization: remarkable orientation effect in mixed cuprate pi complexes. AB - They "know" where to go: a powerful orientation effect has been observed in complexes of mixed organocuprates [R(T)R(NT)CuLi] and substrates with C-C, C-N, and C-S double bonds (see scheme; Th=thienyl). The preferred geometry of the intermediate complex sets up the facile addition of R(T) to the double bond, rather than addition of the "dummy ligand", R(NT) . PMID- 22298493 TI - Conjugated hyperbranched poly(aryleneethynylene)s: synthesis, photophysical properties, superquenching by explosive, photopatternability, and tunable high refractive indices. AB - Triphenylamine (TPA)-based conjugated hyperbranched poly(aryleneethynylene)s (PAEs), hb-P1/2, hb-P1/3, and hb-P1/4, were synthesized with high molecular weights and good solubilities through Sonogashira coupling reactions. These PAEs exhibited outstanding thermal stabilities and different emission behaviors. Tetraphenylethene (TPE)-containing hb-P1/2 fluoresced faintly in THF, although its light emission was enhanced by aggregate formation in aqueous media or in thin films, thereby exhibiting an aggregation-induced emission-enhancement (AIEE) effect. Whereas 1,1,2,3,4,5-hexaphenylsilole (HPS)-bearing hb-P1/3 showed no significant change in emission intensity with increasing water content in aqueous media, hb-P1/4, which consisted of TPA-fluorenone donor-acceptor groups, presented almost identical absorptions, but both positive and negative solvatochromic emissions in various solvents. A superquenching effect was observed in the picric-acid-detection process by using nanosuspensions of hb P1/2. All of the polymers possessed good film formability. UV irradiation of the thin films induced simultaneous photobleaching and cross-linking, thus making them applicable in the fabrication of 2D and 3D patterns. Furthermore, the polymer films also showed high refractive indices, which were tunable upon exposure to UV light. PMID- 22298495 TI - Palladium-catalyzed dehydrative heck olefination of secondary aryl alcohols in ionic liquids: towards a waste-free strategy for tandem synthesis of stilbenoids. AB - All in one: a tandem strategy has been developed wherein secondary aryl alcohols are directly coupled with aryl halides to provide stilbenoids through a dehydrative Heck sequence in the ionic liquid [hmim]Br, and with water as a by product under microwave irradiation. Classical methods do not permit this sequence to proceed in one pot, and some methods require multiple steps. hmim=1-n hexyl-3-methylimidazolium. PMID- 22298496 TI - Rate-controlling isomerizations in fatty acid oxidations by a cytochrome P450 compound I. PMID- 22298497 TI - Controlled radical polymerization mediated by amine-bis(phenolate) iron(III) complexes. AB - Tetradentate amine-bis(phenolate) iron(III) halide complexes containing chloro substituents on the aromatic ring are extremely efficient catalysts for controlled radical polymerization. Molecular weights are in good agreement with theoretical values and polydispersity indexes (PDIs) are as low as 1.11 for styrene and methyl methacrylate polymerizations. Complexes containing alkyl substituents on the aromatic ring are less efficient. Kinetic data reveal activity for styrene polymerization among the fastest reported to date and initial studies implicate a multimechanism system. Despite the highly colored polymerization media, simple work-up procedures yield pure white polymers. PMID- 22298498 TI - Electric-field enhancement inducing near-infrared two-photon absorption in an indium-tin oxide nanoparticle film. AB - An enhancing factor: the enhancement of the electric properties of a dye molecule (IR26) by indium-tin oxide nanoparticles (ITO NPs, see picture) has been shown by measuring the near-infrared two-photon-excited transient absorption spectra. The dye molecule was excited much more efficiently in the presence of an ITO NP layer. PMID- 22298499 TI - Developing a millifluidic platform for the synthesis of ultrasmall nanoclusters: ultrasmall copper nanoclusters as a case study. AB - The future of lab-on-a-chip devices for the synthesis of nanomaterials hinges on the successful development of high-throughput methods with better control over their size. While significant effort in this direction mainly focuses on developing "difficult to fabricate" complex microfluidic reactors, scant attention has been paid to the "easy to fabricate" and simple millifluidic systems that could provide the required control as well as high throughput. By utilizing numerical simulation of fluids within the millifluidic space at different flow rates, the results presented here show velocity profiles and residence time distributions similar to the case of microfluidics. By significantly reducing the residence time and residence time distribution, a continuous flow synthesis of ultrasmall copper nanoclusters (UCNCs) with exceptional colloidal stability is achieved. In-situ synchrotron-radiation-based X-ray absorption spectroscopy (XAS) reveal that the as-prepared clusters are about 1 nm, which is further supported by transmission electron microscopy and UV vis spectroscopy studies. The clusters reported here are the smallest ever produced using a lab-on-a-chip platform. When supported on silica, they are found to efficiently catalyze C-H oxidation reactions, hitherto unknown to be catalyzed by Cu. This work suggests that a millifluidic platform can be an inexpensive, versatile, easy-to-use, and powerful tool for nanoparticle synthesis in general, and more specifically for ultrasmall nanoclusters (UNCs). PMID- 22298500 TI - Carborane photochemistry triggered by aryl substitution: carborane-based dyads with phenyl carbazoles. AB - A bright combination: a new type of donor-acceptor dyad, carbazolylaryl substituted ortho-carboranes, which are conveniently prepared from the corresponding acetylenes and decaborane pathways, showed unique excited-state behavior associated with electron transfer unlike the meta- and para counterparts. PMID- 22298501 TI - Predictors and time trends in clopidogrel and proton pump inhibitor coprescription with low-dose acetylsalicylic acid. AB - PURPOSE: To determine trends and predictors of clopidogrel and proton pump inhibitor (PPI) coprescription with low-dose acetylsalicylic acid (ASA) prescribed for secondary cardiovascular or cerebrovascular disease (CVD) prevention in UK primary care. METHODS: Patients aged 50-84 years who received a first prescription for low-dose ASA for secondary CVD prevention in 2000-2001 (n = 10,330) or 2006-2007 (n = 8154) were identified in The Health Improvement Network UK primary care database. Clopidogrel or PPI coprescriptions received within 15 days after the first low-dose ASA prescription were ascertained. RESULTS: Clopidogrel coprescription with low-dose ASA increased from 1.6% to 25.2% between the two study periods; PPI coprescription increased from 11.6% to 28.3%. Low-dose ASA indications of myocardial infarction [odds ratio (OR) 11.7, 95% confidence interval (CI) 10.2 to 13.4] and unstable angina (OR 1.73, 95%CI 1.09 to 2.75) were positive predictors of clopidogrel coprescription in 2006 2007, relative to chronic ischaemic heart disease. Patients at high risk of upper gastrointestinal bleeding were more likely to receive a PPI than those at lower risk in 2006-2007 (OR 4.36, 95%CI 3.93 to 4.84). In this period, 65.5% of patients who required a clopidogrel coprescription according to guideline recommendations received one, and 44.3% of patients at high risk of upper gastrointestinal bleeding received a PPI. CONCLUSION: Clopidogrel and PPI coprescription with low-dose ASA increased markedly between 2000-2001 and 2006 2007; however, many patients on low-dose ASA did not receive the recommended coprescriptions at the end of the study period. PMID- 22298502 TI - An autonomous and controllable light-driven DNA walking device. PMID- 22298503 TI - Preparation of neutron-activatable holmium nanoparticles for the treatment of ovarian cancer metastases. AB - Nanoparticles containing stable holmium ((165) Ho) are prepared by nanotemplate engineering and subsequently irradiated in a neutron flux to yield (166) Ho, a beta-emitting radiotherapeutic isotope. After intraperitoneal injection to mice bearing SKOV-3 ovarian tumors, significant tumor accumulation of the (166) Ho nanoparticles is observed by SPECT imaging indicating the potential of these neutron activatable nanoparticles for internal radiation therapy of ovarian cancer metastases. PMID- 22298504 TI - Direct to consumer Internet advertising of statins: an assessment of safety. AB - PURPOSE: To evaluate a sample of Internet sites advertising statins for sale to the general public. METHODS: A simulated customer search and evaluation of retrieved sites using evaluation tools focussing on quality (Q) and safe medicine use (SMU). Sites retrieved on 17 November 2010 were systematically analysed from 19 November to 23 December 2010. RESULTS: One hundred eighty-four sites met the inclusion criteria: 40 each for atorvastatin, pravastatin, rosuvastatin, and simvastatin and 24 for fluvastatin. Sites originated from 17 different countries. Most sites scored less than half the maximum Q score (26; range 5-17). Mean total SMU scores for each statin group were lower than 50% of the maximum (45; range of 0-28). There were no statistically significant differences between statins. General contraindications were absent in 92.4% of sites and contraindicated medicines in 47.3%. Key warnings on the appearance of symptoms associated with myopathy, liver disease, hypersensitivity, and pancreatitis were absent in 37, 48.4, 91.3, and 96.2% of sites, respectively. Most websites presented a chaotic and incomplete list of known side effects; just 13 (7.1%) presented a list compatible with current prescribing information. Only two-thirds (65.8%) attempted to describe any in lay language. CONCLUSIONS: A potential purchaser of statins is likely to encounter websites from a wide geographical base and of generally poor quality. This has potentially serious implications for the safety of purchasers who may not be aware of the problems associated with ordering medicines online or the actual medication, which they receive. Direct to consumer advertising websites need tighter controls. PMID- 22298506 TI - Fine-needle aspiration of intrapancreatic accessory spleen: cytomorphologic features and differential diagnosis. AB - BACKGROUND: Intrapancreatic accessory spleen (IPAS) is a rare benign lesion of the pancreas that frequently clinically and radiographically mimics a solid neoplasm. Very rarely, epidermoid cysts may form in IPAS and be mistaken for a cystic neoplasm of the pancreas on radiographic imaging. IPAS and epidermoid cyst involving intrapancreatic cyst (ECIPAS) are benign, and, if recognized, do not require surgical intervention. There are few reports of the cytopathologic features of IPAS diagnosed by fine-needle aspiration (FNA). METHODS: Here we report a series of 6 cases of endoscopic ultrasound (EUS)-guided FNA of IPAS, 3 of which had histological confirmation, including 1 case of histologically confirmed ECIPAS. RESULTS: Cytomorphologic features of IPAS include a polymorphous population of hematopoietic cells, including lymphocytes, eosinophils, histiocytes, plasma cells, and red blood cells, admixed with numerous small blood vessels representing splenic sinusoids. CD8 immunostaining of cell block or core biopsy material highlights splenic endothelial cells and confirms the diagnosis. FNA of ECIPAS reveals predominantly macrophages and proteinaceous debris. CONCLUSIONS: Diagnostic pitfalls include pancreatic neuroendocrine tumor. If IPAS is recognized as a diagnostic consideration on EUS FNA, unnecessary surgical resection may be avoided. PMID- 22298507 TI - Arylsulfonylacetylenes as alkynylating reagents of Csp2-H bonds activated with lithium bases. AB - Chameleon: a new strategy for the synthesis of a wide variety of alkynyl derivatives by the reaction of substituted arylsulfonylacetylenes with organolithium species is described. The high yields, the simplicity of the experimental procedure, the broad scope of this reaction, and the formation of C(sp)-C(sp2) bonds without using transition metals are the main features of this methodology. PMID- 22298508 TI - Operational stability of organic field-effect transistors. AB - Organic field-effect transistors (OFETs) are considered in technological applications for which low cost or mechanical flexibility are crucial factors. The environmental stability of the organic semiconductors used in OFETs has improved to a level that is now sufficient for commercialization. However, serious problems remain with the stability of OFETs under operation. The causes for this have remained elusive for many years. Surface potentiometry together with theoretical modeling provide new insights into the mechanisms limiting the operational stability. These indicate that redox reactions involving water are involved in an exchange of mobile charges in the semiconductor with protons in the gate dielectric. This mechanism elucidates the established key role of water and leads in a natural way to a universal "stress function", describing the stretched exponential-like time dependence ubiquitously observed. Further study is needed to determine the generality of the mechanism and the role of other mechanisms. PMID- 22298509 TI - Disparity in the DNA translocase domains of SWI/SNF and ISW2. AB - An ATP-dependent DNA translocase domain consisting of seven conserved motifs is a general feature of all ATP-dependent chromatin remodelers. While motifs on the ATPase domains of the yeast SWI/SNF and ISWI families of remodelers are highly conserved, the ATPase domains of these complexes appear not to be functionally interchangeable. We found one reason that may account for this is the ATPase domains interact differently with nucleosomes even though both associate with nucleosomal DNA 17-18 bp from the dyad axis. The cleft formed between the two lobes of the ISW2 ATPase domain is bound to nucleosomal DNA and Isw2 associates with the side of nucleosomal DNA away from the histone octamer. The ATPase domain of SWI/SNF binds to the same region of nucleosomal DNA, but is bound outside of the cleft region. The catalytic subunit of SWI/SNF also appears to intercalate between the DNA gyre and histone octamer. The altered interactions of SWI/SNF with DNA are specific to nucleosomes and do not occur with free DNA. These differences are likely mediated through interactions with the histone surface. The placement of SWI/SNF between the octamer and DNA could make it easier to disrupt histone-DNA interactions. PMID- 22298510 TI - An on-bead tailing/ligation approach for sequencing resin-bound RNA libraries. AB - Nucleic acids possess the unique property of being enzymatically amplifiable, and have therefore been a popular choice for the combinatorial selection of functional sequences, such as aptamers or ribozymes. However, amplification typically requires known sequence segments that serve as primer binding sites, which can be limiting for certain applications, like the screening of on-bead libraries. Here, we report a method to amplify and sequence on-bead RNA libraries that requires not more than five known nucleotides. A key element is the attachment of the starting nucleoside to the synthesis resin via the nucleobase, which leaves the 3'-OH group accessible to subsequent enzymatic manipulations. After split-and-mix synthesis of the oligonucleotide library and deprotection, a poly(A)-tail can be efficiently added to this free 3'-hydroxyl terminus by Escherichia coli poly(A) polymerase that serves as an anchored primer binding site for reverse transcription. The cDNA is joined to a DNA adapter by T4 DNA ligase. PCR amplification yielded single-band products that could be cloned and sequenced starting from individual polystyrene beads. The method described here makes the selection of functional RNAs from on-bead RNA libraries more attractive due to increased flexibility in library design, higher yields of full-length sequence on bead and robust sequence determination. PMID- 22298512 TI - Abstracts of the 9th Annual Conference of the American Psychosocial Oncology Society. February 23-25, 2012. Miami, Florida, USA. PMID- 22298511 TI - Fidelity of tRNA 5'-maturation: a possible basis for the functional dependence of archaeal and eukaryal RNase P on multiple protein cofactors. AB - RNase P, which catalyzes tRNA 5'-maturation, typically comprises a catalytic RNase P RNA (RPR) and a varying number of RNase P proteins (RPPs): 1 in bacteria, at least 4 in archaea and 9 in eukarya. The four archaeal RPPs have eukaryotic homologs and function as heterodimers (POP5*RPP30 and RPP21*RPP29). By studying the archaeal Methanocaldococcus jannaschii RPR's cis cleavage of precursor tRNA(Gln) (pre-tRNA(Gln)), which lacks certain consensus structures/sequences needed for substrate recognition, we demonstrate that RPP21*RPP29 and POP5*RPP30 can rescue the RPR's mis-cleavage tendency independently by 4-fold and together by 25-fold, suggesting that they operate by distinct mechanisms. This synergistic and preferential shift toward correct cleavage results from the ability of archaeal RPPs to selectively increase the RPR's apparent rate of correct cleavage by 11,140-fold, compared to only 480-fold for mis-cleavage. Moreover, POP5*RPP30, like the bacterial RPP, helps normalize the RPR's rates of cleavage of non consensus and consensus pre-tRNAs. We also show that archaeal and eukaryal RNase P, compared to their bacterial relatives, exhibit higher fidelity of 5' maturation of pre-tRNA(Gln) and some of its mutant derivatives. Our results suggest that protein-rich RNase P variants might have evolved to support flexibility in substrate recognition while catalyzing efficient, high-fidelity 5' processing. PMID- 22298514 TI - Knowledge exchange and the Journal of Investigative and Clinical Dentistry. PMID- 22298513 TI - Disordered porphyrin metabolism: a potential biological marker for autism risk assessment. AB - Autism (AUT) is a complex neurodevelopmental disorder that, together with Asperger's syndrome and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS), comprises the expanded classification of autistic spectrum disorder (ASD). The heterogeneity of ASD underlies the need to identify biomarkers or clinical features that can be employed to identify meaningful subtypes of ASD, define specific etiologies, and inform intervention and treatment options. Previous studies have shown that disordered porphyrin metabolism, manifested principally as significantly elevated urinary concentrations of pentacarboxyl (penta) and coproporphyrins, is commonly observed among some children with ASD. Here, we extend these observations by specifically evaluating penta and coproporphyrins as biological indicators of ASD among 76 male children comprising 30 with validated AUT, 14 with PDD-NOS, and 32 neurotypical (NT) controls. ASD children (AUT and PDD-NOS) had higher mean urinary penta (P < 0.006) and copro (P < 0.006) concentrations compared with same-aged NT children, each characterized by a number of extreme values. Using Receiver Operating Characteristic curve analysis, we evaluated the sensitivity and specificity of penta, copro, and their combined Z-scores in ASD detection. The penta sensitivity was 30% for AUT and 36% for PDD-NOS, with 94% specificity. The copro sensitivity was 33% and 14%, respectively, with 94% specificity. The combined Z-score measure had 33% and 21% sensitivity for AUT and PDD-NOS, respectively, with 100% specificity. These findings demonstrate that porphyrin measures are strong predictors of both AUT and PDD-NOS, and support the potential clinical utility of urinary porphyrin measures for identifying a subgroup of ASD subjects in whom disordered porphyrin metabolism may be a salient characteristic. PMID- 22298515 TI - Cure mechanisms in materials for use in esthetic dentistry. AB - The current paper reviews the curing mechanisms found in resin-based materials used in dentistry. Historical aspects of dental products and the associated curing mechanisms are reviewed. In comparison with common industrial procedures, curing methods employed for dental materials are relatively limited because of the need to polymerize quickly in the oral cavity at an ambient temperature. Heat cure and self-cure dental resins utilize benzoyl peroxide initiator alone with a tertiary amine co-initiator. At present, most dental restorative composites use a camphorquinone-amine complex initiation, visible light-cure, one-component systems, although alternative photoinitiators have been researched and developed. A multiple curing mode in a dual-cure material is a complex combination of various initiation systems. The use of aryl sulfinic acid sodium salt to overcome adverse chemical interactions between simplified adhesives and self- or dual-cure composites is based on another self-cure polymerization mechanism, sulfinic acid initiated polymerization, proposed by Hagger in 1948. The sodium salt of aryl sulfinic acid reacts with an acidic monomer in simplified adhesives, and is believed to produce radicals. Clinically, it is important to try to optimize the degree of conversion of resin-based materials using proper manipulation and adequate light-curing techniques to ensure the best outcome for materials used to restore teeth. PMID- 22298516 TI - Is the consumption of fruit cariogenic? AB - AIM: The aim of this study was to investigate possible risk factors for dental caries in primary school children. METHODS: Children aged 10-12 years (n = 257) residing in Lithgow, a non-fluoridated community in New South Wales, Australia, were examined for caries experience in the permanent dentition. Information on dental practices, diet, residential movements, and socioeconomic status were obtained from self-completed questionnaires. RESULTS: Caries risk in the permanent teeth was associated with social disadvantage and diet. Among the dietary factors, the frequency of fruit consumption was associated with higher odds of caries experience (odds ratio: 1.52, 95% confidence intervals: 1.05, 2.21). CONCLUSIONS: Exposure to a high level of fruit consumption was suggestive of increased caries risk. Longitudinal studies are required to investigate the relationship between fruit consumption and dental caries. PMID- 22298517 TI - Exploring taste hyposensitivity in Japanese senior high school students. AB - AIM: The main objective of this study was to investigate the prevalence of taste hyposensitivity and the relationships between sex, oral health status, and eating habits with taste hyposensitivity in Japanese senior high school students. METHODS: Oral examinations, sweet and salt whole-mouth taste tests, and a questionnaire about eating habits were conducted on 234 senior high school students. Factors affecting taste hyposensitivity were investigated using a multivariate analysis. RESULTS: Sweet-taste hyposensitivity was observed in 7.3% of the students, and salt-taste hyposensitivity in 22.2%. Approximately 3% of the students had both sweet- and salt-taste hyposensitivity, and 22.6% had either sweet- or salt-taste hyposensitivity. In total, 26% had a taste hyposensitivity. There were significant relationships between the intake of instant noodles with sweet-taste hyposensitivity, and the intake of vegetables or isotonic drinks with salt-taste hyposensitivity. CONCLUSIONS: There was a significant association between eating habits and taste hyposensitivity in Japanese senior high school students. Taste tests would be a helpful adjunct for students to recognize variations in taste sensitivity, and a questionnaire about their eating habits might provide an effective self-review of their eating habits, and therefore, provide motivation to change. PMID- 22298518 TI - Investigation of the incidence of stylohyoid ligament calcifications with panoramic radiographs. AB - AIM: This study examined and classified patients who were treated at the Faculty of Dentistry at Ankara University Dentistry to determine the incidence of different types of stylohyoid ligament calcification (SLC) using panoramic radiographs. In addition, it also assessed the possible causative symptoms and Eagle's syndrome in cases of styloid process elongation. METHODS: The study consisted of 2000 patients (1161 females and 839 males), aged 3-88 years, who were treated at our clinic. The panoramic radiographs were evaluated as part of this study. RESULTS: Panoramic radiography examination revealed SLC in 1350 patients. Both-sided (right and left), type 1 SLC was observed in 345 patients, while types 2-4 were found in 203, 418, and 384 patients, respectively. CONCLUSION: The incidence of SLC was found to be higher in female patients when compared to male patients. In addition, calcifications were seen more often at age 50-59 years, and the incidence of calcification was found to increase with age. Two Eagle's syndrome cases were diagnosed among a total of 2000 patients. Finally, it was determined that the incidence of calcified stylohyoid ligament is higher in patients with systemic diseases. PMID- 22298519 TI - Computer-aided measurement of mandibular cortical width on dental panoramic radiographs for identifying osteoporosis. AB - AIM: To develop a computer-aided diagnosis system to continuously measure mandibular inferior cortical width on dental panoramic radiographs and evaluate the system's efficacy in identifying postmenopausal women with low-skeletal bone mineral density. METHODS: Mandibular inferior cortical width was continuously measured by enhancing the original X-ray image, determining cortical boundaries, and evaluating all distances between the upper and lower boundaries in the region of interest. The system's efficacy in identifying osteoporosis at the lumbar spine and the femoral neck was evaluated for 100 women (>=50 years): 50 in the development of the tool and 50 in its validation. RESULTS: The sensitivity and specificity of the cortical measurements for identifying the development patients were 90% (95% confidence interval shown in parentheses) (63.0-87.0) in women with low spinal bone mineral density, and 81.8% (70.1-91.8) and 69.2% (56.2-81.8) in those with low femoral bone mineral density, respectively. Corresponding values in the validation patients were 93.3% (85.9-100) and 82.9% (71.4-92.7) at the lumbar spine, and 92.3% (84.5-99.5) and 75.7% (63.0-87.0) at the femoral neck, respectively. CONCLUSION: Our new computer-aided diagnosis system is a useful procedure in triage screening for osteoporosis. PMID- 22298520 TI - Effect of complete edentulism on masseter muscle thickness and changes after complete denture rehabilitation: an ultrasonographic study. AB - AIM: The aim of the present study was to determine the changes in masseter muscle thickness due to the state of complete edentulism and the effect of complete denture rehabilitation on the masseter muscle. METHODS: Real-time ultrasonography of the masseter muscle at relaxed and contracted states was carried out for twelve patients (six dentulous and six completely edentulous). Edentulous patients were scanned at the time of denture insertion and at the end of 3 months' follow up. RESULTS: The mean masseter muscle thickness of the edentulous patients was significantly increased after the 3-month follow-up than the thickness at the time of denture insertion, but was significantly lower than that of the dentulous patients of the same age group. CONCLUSION: Within the limitations of this study, it can be concluded that change occurs in the masseter muscle thickness after rehabilitation with complete dentures in the form of increased muscle thickness. However, the thickness of the muscle remains smaller than that of dentate individuals. PMID- 22298521 TI - Prevalence of oral Candida carriage in Thai adolescents. AB - AIM: Oral candidiasis is among the most common AIDS-associated opportunistic infections. Adolescents remain at the highest risk of HIV infection and could suffer from oral candidiasis. However, information on oral Candida carriage in this population is limited. This study aims to evaluate the prevalence of oral Candida in Thai adolescents. METHODS: Oral rinse samples from 80 healthy Thais (age: 15-17 years) were collected and analyzed for the prevalence of Candida species using culture-based and polymerase chain reaction assays. RESULTS: Twenty six adolescents (32.5%) carried Candida in the oral cavity. Candida albicans was detected in 28.75% (23/80). Non-albicans Candida species were detected in 6.25% (5/80). The majority (92.3%, 24/26) of adolescents with Candida carried a single species. Two carried two species: one with Candida glabrata and Candida albicans, and the other with Candida parapsilosis and Candida albicans. Three adolescents harbored only non-albicans species, with one carrying Candida tropicalis and two carrying Candida parapsilosis. Candida dubliniensis was not detected in this population. Most adolescents carried Candida at a low level (<500 c.f.u./mL). CONCLUSIONS: Oral Candida was present in approximately one-third of adolescents. Candida albicans was the most prevalent (88.5%), and non-albicans species were present in 19.2% of those with oral Candida. PMID- 22298522 TI - Acid production and growth by oral Lactobacillus species in vitro. AB - AIM: To analyze the acid-producing and growth abilities of different oral Lactobacillus species. METHODS: Thirty-nine oral clinical strains and type strains of Lactobacillus, representing nine species, including Lactobacillus casei/paracasei, Lactobacillus fermentum, Lactobacillus gasseri, Lactobacillus mucosae, Lactobacillus oris, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus salivarius, and Lactobacillus vaginalis were studied. Anaerobically grown bacterial cells were inoculated overnight in de Man, Rogosa, and Sharpe broth containing 2% glucose (pH 7.0). Acid production and growth were measured at 0, 1.5, 3, 5, 7, and 24 h. RESULTS: Lactobacillus salivarius, Lactobacillus rhamnosus, Lactobacillus casei/paracasei, and Lactobacillus plantarum grew rapidly and reached an optical density higher than other species. They also produced more acid than the others. Lactobacillus vaginalis showed the lowest rate of growth and acid production. These findings demonstrated that the different species of Lactobacillus showed different abilities to generate acid, allowing the species to be categorized into three groups: strongly, moderately, and weakly acidogenic. CONCLUSION: There was variation in acid production and growth between the Lactobacillus species. The strongest acid producers were Lactobacillus salivarius, Lactobacillus rhamnosus, Lactobacillus plantarum, and Lactobacillus casei/paracasei, respectively. It seems possible that these species might play a more important role in caries development than the others. PMID- 22298523 TI - School teachers' knowledge of oral disease prevention: a survey from Dharwad, India. AB - AIM: To assess knowledge and the associated factors among Indian school teachers towards oral disease. METHODS: A cross-sectional design was employed using a self administered questionnaire. A total of 215 school teachers were selected, with a response rate of 95.3% (n = 205). RESULTS: A total of 35.6% of school teachers had "good" knowledge, while 42.4% had "medium" knowledge of the prevention of oral disease. Knowledge of dental caries was highest, as opposed to oral cancer, which was lowest. School teachers aged >50 years and those with postgraduate degrees had greater knowledge. A significant association was observed between teachers' levels of knowledge and their age groups (chi(2) = 20.9950, P < 0.05) and education level (chi(2) = 13.9740, P < 0.05). However, the multivariate stepwise regression analysis showed that education, age group, sex, and type of institutional funding (public/private) was significantly correlated to knowledge (R(2) = 0.1250, P < 0.05). CONCLUSIONS: The study revealed that school teachers, in particular younger teachers and those with only basic educational qualifications, need to be further motivated to improve their awareness and knowledge about oral diseases. Therefore, the establishment of school-based oral health promotion programs in India with immediate effects is essential. PMID- 22298524 TI - Melanotic neuroectodermal tumor of infancy: a histopathological and immunohistochemical study. AB - Melanotic neuroectodermal tumor of infancy is an uncommon neoplasm that normally occurs in the anterior maxilla of children less than 1 year of age. This is a tumor with controversial origin, although neural crest origin is proposed. This case report presents an analysis of histopathological and immunohistochemical findings in this rare tumor. PMID- 22298525 TI - Use of triple antibiotic paste in the treatment of large periradicular lesions. AB - Microorganisms are the possible source of endodontic lesions. The polymicrobial infection makes the sterilization of the root canal difficult. The following case report describes the non-surgical endodontic treatment of teeth with a large periradicular lesion. First, an intracanal dressing of calcium hydroxide was given. Since the symptoms did not subside, the treatment protocol was changed. A triple antibiotic paste was used instead for 3 months. On follow up, teeth were clinically asymptomatic and radiographically showed healing of the periradicular lesion. The result of the case show that when most commonly-used medicaments fail in eliminating the symptoms, then a triple antibiotic paste (metronidazole, ciprofloxacin, and minocycline) can be used clinically in the treatment of teeth with large periradicular lesions. PMID- 22298526 TI - Monitoring the glioma tropism of bone marrow-derived progenitor cells by 2-photon laser scanning microscopy and positron emission tomography. AB - Intracerebral experimental gliomas attract intravenously injected murine or human bone marrow-derived hematopoietic progenitor and stem cells (HPC) in vitro, ex vivo, and in vivo, indicating that these progenitor cells might be suitable vehicles for a cell-based delivery of therapeutic molecules to malignant gliomas. With regard to therapeutic application, it is important to investigate cell fates in vivo (i.e., the time-dependent intratumoral and systemic distribution after intravenously injection). Conventional histological analysis has limitations in this regard because longitudinal monitoring is precluded. Here, we used 2-photon laser scanning microscopy (2PLSM), positron emission tomography (PET), and MRI to study the fate of intravenously injected HPC carrying fluorescence, bioluminescence, and PET reporter genes in glioma-bearing mice. Our 2PLSM-based monitoring studies revealed that HPC homing to intracerebral experimental gliomas occurred already within the first 6 h and was most efficient within the first 24 h after intravenous injection. The highest PET signals were detected in intracerebral gliomas, whereas the tracer uptake in other organs, notably spleen, lung, liver, and muscle, remained at background levels. The results have important implications for designing schedules for therapeutic cell-based anti glioma approaches. Moreover, the PET reporter-based imaging technique will allow noninvasive monitoring of cell fate in future cell-based therapeutic antiglioma approaches. PMID- 22298527 TI - Trichostatin A abrogates airway constriction, but not inflammation, in murine and human asthma models. AB - Histone deacetylase (HDAC) inhibitors may offer novel approaches in the treatment of asthma. We postulate that trichostatin A (TSA), a Class 1 and 2 inhibitor of HDAC, inhibits airway hyperresponsiveness in antigen-challenged mice. Mice were sensitized and challenged with Aspergillus fumigatus antigen (AF) and treated with TSA, dexamethasone, or vehicle. Lung resistance (R(L)) and dynamic compliance were measured, and bronchial alveolar lavage fluid (BALF) was analyzed for numbers of leukocytes and concentrations of cytokines. Human precision-cut lung slices (PCLS) were treated with TSA and their agonist-induced bronchoconstriction was measured, and TSA-treated human airway smooth muscle (ASM) cells were evaluated for the agonist-induced activation of Rho and intracellular release of Ca(2+). The activity of HDAC in murine lungs was enhanced by antigen and abrogated by TSA. TSA also inhibited methacholine (Mch) induced increases in R(L) and decreases in dynamic compliance in naive control mice and in AF-sensitized and -challenged mice. Total cell counts, concentrations of IL-4, and numbers of eosinophils in BALF were unchanged in mice treated with TSA or vehicle, whereas dexamethasone inhibited the numbers of eosinophils in BALF and concentrations of IL-4. TSA inhibited the carbachol-induced contraction of PCLS. Treatment with TSA inhibited the intracellular release of Ca(2+) in ASM cells in response to histamine, without affecting the activation of Rho. The inhibition of HDAC abrogates airway hyperresponsiveness to Mch in both naive and antigen-challenged mice. TSA inhibits the agonist-induced contraction of PCLS and mobilization of Ca(2+) in ASM cells. Thus, HDAC inhibitors demonstrate a mechanism of action distinct from that of anti-inflammatory agents such as steroids, and represent a promising therapeutic agent for airway disease. PMID- 22298528 TI - Antiinflammatory role of MUC1 mucin during infection with nontypeable Haemophilus influenzae. AB - MUC1 (or Muc1 in nonhuman species) is a membrane-tethered mucin expressed on the apical surface of mucosal epithelia (including those of the airways) that suppresses Toll-like receptor (TLR) signaling. We sought to determine whether the anti-inflammatory effect of MUC1 is operative during infection with nontypeable Haemophilus influenzae (NTHi), and if so, which TLR pathway was affected. Our results showed that: (1) a lysate of NTHi increased the early release of IL-8 and later production of MUC1 protein by A549 cells in dose-dependent and time dependent manners, compared with vehicle control; (2) both effects were attenuated after transfection of the cells with a TLR2-targeting small interfering (si) RNA, compared with a control siRNA; (3) the NTHi-induced release of IL-8 was suppressed by an overexpression of MUC1, and was enhanced by the knockdown of MUC1; (4) the TNF-alpha released after treatment with NTHi was sufficient to up-regulate MUC1, which was completely inhibited by pretreatment with a soluble TNF-alpha receptor; and (5) primary murine tracheal surface epithelial (MTSE) cells from Muc1 knockout mice exhibited an increased in vitro production of NTHi-stimulated keratinocyte chemoattractant compared with MTSE cells from Muc1-expressing animals. These results suggest a hypothetical feedback loop model whereby NTHi activates TLRs (mainly TLR2) in airway epithelial cells, leading to the increased production of TNF-alpha and IL-8, which subsequently up regulate the expression of MUC1, resulting in suppressed TLR signaling and decreased production of IL-8. This report is the first, to the best of our knowledge, demonstrating that the inflammatory response in airway epithelial cells during infection with NTHi is controlled by MUC1 mucin, mainly through the suppression of TLR2 signaling. PMID- 22298529 TI - Lipoprotein receptor-related protein 1 regulates collagen 1 expression, proteolysis, and migration in human pleural mesothelial cells. AB - The low-density lipoprotein receptor-related protein 1 (LRP-1) binds and can internalize a diverse group of ligands, including members of the fibrinolytic pathway, urokinase plasminogen activator (uPA), and its receptor, uPAR. In this study, we characterized the role of LRP-1 in uPAR processing, collagen synthesis, proteolysis, and migration in pleural mesothelial cells (PMCs). When PMCs were treated with the proinflammatory cytokines TNF-alpha and IL-1beta, LRP-1 significantly decreased at the mRNA and protein levels (70 and 90%, respectively; P < 0.05). Consequently, uPA-mediated uPAR internalization was reduced by 80% in the presence of TNF-alpha or IL-1beta (P < 0.05). In parallel studies, LRP-1 neutralization with receptor-associated protein (RAP) significantly reduced uPA dependent uPAR internalization and increased uPAR stability in PMCs. LRP-1 deficient cells demonstrated increased uPAR t(1/2) versus LRP-1-expressing PMCs. uPA enzymatic activity was also increased in LRP-1-deficient and neutralized cells, and RAP potentiated uPA-dependent migration in PMCs. Collagen expression in PMCs was also induced by uPA, and the effect was potentiated in RAP-treated cells. These studies indicate that TNF-alpha and IL-1beta regulate LRP-1 in PMCs and that LRP-1 thereby contributes to a range of pathophysiologically relevant responses of these cells. PMID- 22298531 TI - Hypoxia-inducible factor 2alpha plays a critical role in the formation of alveoli and surfactant. AB - Alveolarization of the developing lung is an important step toward the switch from intrauterine life to breathing oxygen-rich air after birth. The distal airways structurally change to minimize the gas exchange path, and Type II pneumocytes increase the production of surfactants, which are required to reduce surface tension at the air-liquid interface in the alveolus. Hypoxia-inducible factor 2alpha (Hif2alpha) is an oxygen-regulated transcription factor expressed in endothelial and Type II cells, and its expression increases toward the end of gestation. We investigated the role of Hif2alpha in Type II cells by conditionally expressing an oxygen-insensitive mutant of Hif2alpha in airway epithelial cells during development. Newborn mice expressing the mutant Hif2alpha were born alive but quickly succumbed to respiratory distress. Subsequent analysis of the lungs revealed dilated alveoli covered with enlarged, aberrant Type II cells and a diminished number of Type I cells. The Type II cells accumulated glycogen in part by increased glucose uptake via the up-regulation of the glucose transporter 1. Furthermore, the cells lacked two crucial enzymes involved in the metabolism of glycogen into surfactant lipids, lysophosphatidylcholine acyltransferase and ATP-binding cassette sub-family A member 3. We conclude that Hif2alpha is a key regulator in alveolar maturation and the production of phospholipids by Type II cells. PMID- 22298530 TI - Prostaglandin E2 stimulates the production of vascular endothelial growth factor through the E-prostanoid-2 receptor in cultured human lung fibroblasts. AB - Fibroblasts are the major mesenchymal cells present within the interstitium of the lung and are a major source of vascular endothelial growth factor (VEGF), which modulates the maintenance of pulmonary microvasculature. Prostaglandin E(2) (PGE(2)) acts on a set of E-prostanoid (EP) receptors that activate multiple signal transduction pathways leading to downstream responses. We investigated the modulation by PGE(2) of VEGF release by human lung fibroblasts. Human lung fibroblasts were cultured until reaching 90% confluence in tissue culture plates, after which the culture media were changed to serum-free Dulbecco's modified Eagle's medium, with or without PGE(2), and with specific agonists or antagonists for each EP receptor. After 2 days, culture media were assayed for VEGF by ELISA. The results demonstrated that PGE(2) and the EP2 agonist ONO-AE1-259-01 significantly stimulated the release of VEGF in a concentration-dependent manner. Agonists for other EP receptors did not stimulate the release of VEGF. The stimulatory effect of PGE(2) was blocked by the EP2 antagonist AH6809, but was not blocked by antagonists for other EP receptors. The protein kinase-A (PKA) inhibitor KT-5720 also blocked the stimulatory effect of PGE(2). The increased release of VEGF induced by PGE(2) was accompanied by a transient increase in the concentration of VEGF mRNA. These findings demonstrate that PGE(2) can modulate the release of VEGF by human lung fibroblasts through its actions in the EP2 receptor/PKA pathway. This activity may contribute to the maintenance of pulmonary microvasculature in the alveolar wall. PMID- 22298532 TI - Effects of ethanol on psychomotor performance under steady-state conditions. AB - Ethanol was administered to eight male volunteers using an oral loading dose followed by repeated small oral doses to achieve approximate steady-state drug concentrations in a double-blind placebo controlled cross over design. Ethanol or placebo were administered over a 5-h period in two sessions at least 7 days apart. The effects of ethanol were assessed using a short battery of psychomotor tests and visual analogue scales which was administered repeatedly during the steady-state period, and a long battery administered once before and once during the steady-state period. The concentrations of ethanol in plasma and breath were determined at 20-min intervals. Mean plasma concentrations of 94 mg/100 ml were obtained. Ethanol produced a clear impairment to psychomotor performance, with a 41% increase in body sway, a 61% increase in errors on a maze task, a 6.5% reduction in digit-symbol substitution and an 8% slowing in tapping. Subjective feelings of drunkenness and sedation were noted. No measure showed evidence for acute tolerance, as assessed by comparison of the slopes fitted to the performance measures in the short battery. PMID- 22298533 TI - Effects of psychotropic drugs on digit substitution: comparison of the computerized symbol-digit substitution and traditional digit-symbol substitution tests. AB - The digit-symbol substitution test (DSST), performed with paper and pencil or computerized, is widely used to reveal decrements in human attention and cognition. We programmed sets of adjustable tasks (digit-symbol, digit-digit, symbol-digit, symbol-symbol) into a microcomputer and compared the symbol-digit substitution (SDST) and the digit copying test (DDCT) with the traditional DSST in two placebo-controlled double-blind studies of psychotropic drugs with pre trained young healthy subjects. Performances were measured before drug intake and several times after it; matched, different codes were used at consecutive tests. DSST and SDST substitutions remained at the baseline level after placebo, while the simple DDCT performance improved during the placebo session. The prolonged (3 min) test was not exhaustive because interim counts at 90 s predicted the final performance well. In Trial I, 15 mg diazepam orally reduced DSST and SDST functions in a similar way, but it also impaired simple copying in the DDCT, though to a lesser extent. Ebastine, an H(1)-antihistamine, proved inert alone and failed to increase the effects of diazepam on these variables. In Trial II, 7.5 mg zopiclone, 0.4 mg suriclone and 50 mg chlorpromazine, alone and in combinations, impaired the DSST performance in the manner expected. The drug effects were similar in the SDST, and somewhat less in the DDCT, while the substitution errors were subject related and not altered significantly by any treatment. The simple correlation matrices (Pearson, Spearman), confirmed by analysis of covariance, showed that the results of DSST correlated fairly well with those of SDST after zopiclone, chlorpromazine and their combination, but not after suriclone or its combination with chlorpromazine. The DDCT results correlated with those of the substitution tests when analysing pooled baseline values, but not when analysing the performances after drug intake. Subjective visual analogue variables correlated poorly or not at all with objective performances. Our results suggest that manual dexterity in these computerized tests might contribute significantly to the total impairment of performance in response to different drugs. The DSST and SDST matched each other fairly well in their sensitivity to drug effects, yet this similarity may depend on the drug used. PMID- 22298534 TI - Behavioural effects of scopolamine and the TRH analogue RX77368 on radial arm maze performance in the rat. AB - Effects of repeated intracerebroventricular administration of the thyrotrophin releasing hormone (TRH) analogue, RX77368 (3,3'-dimethyl-TRH, 2 MUg, once daily), on a scopolamine-induced performance deficit in an eight-arm radial maze were evaluated in adult rats. Scopolamine (0.3 mg/kg i.p.-30 min) pre-treatment produced a significant deficit in the number of unrepeated arm entries and total arm entries and increased the percentage of incorrect arm entries and the total time on the maze, compared with saline-treated controls. Prior treatment with RX77368 (40 min before maze testing) produced a partial but significant attenuation of the scopolamine-induced performance deficit on the maze during the first five trials but RX77368 also enhanced maze performance during the same period when given alone. These results suggest that the observed scopolamine induced performance deficit on the radial arm maze partly results from a reduction in locomotion and maze exploration rather than solely impairment of memory, and that RX77368 treatment may improve radial maze performance by increasing arousal and exploratory behaviour in rats rather than directly enhancing cognition. PMID- 22298535 TI - The effect of temazepam on melatonin secretion and light sensitivity. AB - Seven healthy male volunteers had their light sensitivity (melatonin suppression) and melatonin phase measured before and after treatment with temazepam (20 mg) for 7 days. Temazepam did not alter the circadian phase of melatonin secretion (the Dim Light Melatonin Onset, the timing of the peak of secretion), the total melatonin secretion nor the sensitivity of melatonin secretion to suppression by full spectrum light. This is an important negative finding which suggests that the short half-life benzodiazepine hypnotic temazepam does not confound tests of light sensitivity or melatonin phase. PMID- 22298536 TI - A double-blind controlled comparison of fluoxetine and lofepramine in major depressive illness. AB - One hundred and eighty three patients with DSM-III-R major depressive illness were allocated randomly to treatment with one of two new generation antidepressants, fluoxetine and lofepramine. Both patient groups had significantly lower mean scores on the Hamilton Depression Rating Scale (HDRS) 6 weeks after entry to the trial (p < 0.001), but there were no differences between the groups, either at baseline or after 6 weeks, in total HRDS score or in subscores for anxiety or suicidality. Anticholinergic side effects were commoner with lofepramine; adverse effects were on the whole mild and few patients dropped out because of them. This study does not support previous claims of specific adverse effects of fluoxetine on anxiety and suicidality. PMID- 22298537 TI - Lofepramine--a safe anti-depressant in acute hepatic porphyria? AB - The acute porphyrias are a group of neuropsychiatric disorders in which a life threatening crisis can be precipitated by a variety of drugs, including antidepressants. Because of the need to find an antidepressant that is safe for porphyria patients, we have studied the effects of lofepramine on porphyria in laboratory rats and porphyria patients. The rats did not exhibit a significant rise in hepatic delta-aminolaevulinic acid synthase activity (a marker of drug porphyrinogenicity) when given the drug compared with its solvent alone. Four porphyria patients exhibited no clinical evidence of disease activation after exposure to the drug. The biochemical activity of their disease was assessed by measurement of the 24-h urinary excretion of delta- aminolaevulinic acid and porphobilinogen (haem precursors formed prior to the metabolic block). No patient exhibited a sustained rise compared to pre-treatment levels, or between low dose and high dose lofepramine. We suggest that lofepramine is probably safe in acute porphyria, but should be used with caution. PMID- 22298538 TI - Aniracetam improves behavioural responses and facilitates signal transduction in the rat brain. AB - The effect of aniracetam (10, 50, 100 mg/kg i.p. daily for 15 days) on both behavioural and biochemical parameters was investigated in the adult rat. Animals given aniracetam (50 mg/kg 1 h before the trial) showed a significant increase in the percentage of conditioned active avoidance responses and a reduction of latency times. Aniracetam significantly counteracted the scopolamine-induced memory failure at the passive avoidance (step down) test, while it did not modify the locomotion of the animals. In purified frontocortical and hippocampal synaptic membranes of rats treated with aniracetam (50 mg/kg i.p. daily for 15 days) a potentiation of basal, carbamylcholine-, dopamine- and norepinephrine stimulated adenylyl cyclase activity was observed, while forskolin-stimulated enzyme activity was not modified. With regard to inositol phosphate production measured in fronto-cortical synaptoneurosomes, aniracetam potentiated the stimulation by angiotensin II, while the stimulation by carbamylcholine, not affected by 10 and 50 mg/kg aniracetam, was notably, although not significantly, decreased by 100 mg/kg aniracetam. Furthermore, in synaptosomes derived from hippocampus, aniracetam (50 mg/kg i.p. daily for 15 days) caused an increase of both basal and K(+)-stimulated intrasynaptosomal Ca(2+) concentration. In conclusion, a correlation between the improvement of behavioural performance and the modulation of transducing systems by aniracetam seems to take place in brain areas, such as frontal cortex and hippocampus, known to play a major role in the control of cognitive functions. PMID- 22298539 TI - Fluvoxamine in the treatment of depressive illness in children and adolescents. PMID- 22298540 TI - The place of chemical pathology in the development of psychopharmacology. PMID- 22298542 TI - Psychotropic drug development--social, scientific and economic issues BAP Autumn Meeting, November 1993. PMID- 22298541 TI - Neuroleptics, oestrogen, post-partum psychiatric disturbance and movement disorder: a case report. PMID- 22298543 TI - Personalized oral health care: providing '-omic' answers to oral health care queries. PMID- 22298544 TI - Tooth survival. PMID- 22298546 TI - Nutrition and cancer. PMID- 22298548 TI - Nerve block. PMID- 22298550 TI - Writing prescriptions. PMID- 22298552 TI - Twenty-four month clinical evaluation of fissure sealants on partially erupted permanent first molars: glass ionomer versus resin-based sealant. AB - BACKGROUND: Glass ionomer sealants are an alternative to resin-based sealants, especially for use in partially erupted permanent molars. The authors conducted a study to compare the retention, marginal staining and cariostatic properties of a glass ionomer sealant with those of a resin-based sealant during a 24-month period. METHODS: We included in this study 39 patients aged 5 through 9 years who had bilateral partially erupted first permanent molars. One of us (S.B.) placed a resin-based sealant (Delton Plus FS+, Dentsply Professional, York, Pa.) (group D) on a partially erupted first molar in one quadrant of the maxilla or mandible and a glass ionomer sealant (GC Fuji Triage White, GC America, Alsip, Ill.) (group T) in the other quadrant. Two masked and calibrated investigators (S.A.A., J.C.) evaluated the sealants for retention, marginal staining and carious lesions at three, six, 12 and 24 months. The authors used a multinomial regression for statistical analysis (P < .05). RESULTS: The recall rate was 69.2 percent at 24 months. Two sealants from group D and three from group T were lost completely. Complete retention rates at 24 months were 40.7 and 44.4 percent for groups D and T, respectively. The authors found no statistically significant difference in retention rates between groups at each recall examination (P > .05). For marginal staining, sealants in the resin-based group exhibited statistically higher marginal staining than did sealants in the glass ionomer group (P < .05). Although the authors detected no caries in teeth in group T, teeth in group D in which the sealant was lost completely experienced demineralization. CONCLUSIONS: Resin-based and glass ionomer sealants exhibited similar retention rates at 24 months. However, marginal staining was lower in the glass ionomer group, and the authors found no caries in teeth in this group. Consequently, glass ionomer sealants may be a better choice when salivary contamination is expected. CLINICAL IMPLICATIONS: Sealing during tooth eruption presents a particular challenge owing to difficulty in isolating the tooth. Glass ionomers may be a better material for sealing partially erupted molars. PMID- 22298553 TI - Immediate postextraction implant placement with immediate loading for maxillary full-arch rehabilitation: A two-year retrospective analysis. AB - BACKGROUND: There are few studies in the literature regarding immediate postextraction implant placement with immediate loading in the maxilla. These studies have only small cohorts. Therefore, the authors conducted a retrospective study to help fill this knowledge gap. METHODS: Between January 2001 and January 2009, 65 participants (32 women, 33 men) with an average age of 60.5 years (age range, 43-83 years) received 334 dental implants, which were placed in postextraction sockets and loaded immediately. The follow-up period for this retrospective study was two years. RESULTS: All prostheses were stable, and only seven implants failed during the follow-up, for a 100 percent prosthetic survival rate and a 97.9 percent implant survival rate at two years. The mean (standard deviation) implant bone level measured 0.50 (0.27) millimeter at insertion, 1.90 (0.51) mm at one year and 2.06 (0.49) mm at two years. CONCLUSIONS: The results of this retrospective study showed that the survival rate of immediately loaded postextraction implants is comparable with that reported for traditional delayed implants in the maxilla. CLINICAL IMPLICATIONS: Immediate loading of four to six implants placed in extraction sockets may be a valid way to treat the edentulous maxilla. PMID- 22298554 TI - Nitrous oxide-oxygen administration: when safety features no longer are safe. AB - BACKGROUND: Nitrous oxide-oxygen sedation is used widely in dentistry because of its relative safety and efficacy. The most important safety consideration is the prevention of hypoxia. Safety features have been designed to prevent hypoxia by ensuring a minimal oxygen flow, thus limiting the amount of nitrous oxide that can be administered. METHODS: The authors review the 12 safety features used to ensure the safety and efficacy of nitrous oxide-oxygen sedation. They provide examples of safety feature failures, as well as steps to follow to help prevent negative outcomes. CONCLUSIONS: Nitrous oxide-oxygen delivery systems typically are limited to a maximum of 70 percent nitrous oxide and 30 percent oxygen delivery, which ensures that the patient is receiving at least 9 percent more oxygen than found in ambient air. Other safety features stop the delivery of nitrous oxide if oxygen flow stops. The pin-index safety system prevents the accidental attachment of a nonoxygen tank to the oxygen attachment portal, and diameter-index systems help ensure that the appropriate gas flows through the appropriate tubing. Although these safety features are in place, dentists have reported incidents of hypoxia involving incorrect equipment installation or equipment damage. Practice Implications. If a safety feature failure is suspected during administration of nitrous oxide-oxygen sedation, the clinician should remove the face mask from the patient immediately. PMID- 22298555 TI - A nonsurgical endodontic treatment in open-apex and immature teeth affected by dens invaginatus: using a collagen membrane as an apical barrier. AB - BACKGROUND: The authors' objective in this case report is to demonstrate an effective nonsurgical endodontic treatment in open-apex teeth affected by dens invaginatus (DI) by using a collagen membrane as an apical barrier and using a mineral trioxide aggregate (MTA) apical plug. CASE DESCRIPTION: . The authors present two cases of DI with open apexes in maxillary lateral incisors. In the first case, an adolescent had bilateral Oehlers type II DI and extensive periradicular radiolucency, internal root resorption and a vestibular fistula in the left maxillary lateral incisor. In the second case, an adult had Oehlers type II DI and an incomplete apex in the left maxillary lateral incisor. For both patients, the clinician placed a collagen membrane through the apexes of the left maxillary incisors to provide a resorbable extraradicular barrier against which MTA cement could be packed. The clinician obturated the adolescent's right lateral incisor. RESULTS: In the adolescent, the vestibular sinus tract was closed after one week. At subsequent follow-up examinations, the periradicular regions were completely healed, and postoperative radiographs revealed good bone healing in the lateral incisors. The teeth were asymptomatic and healing was achieved without any need for further endodontic surgical intervention. In the adult patient, the tooth was symptom free after one week, and radiography performed six months after the procedure showed complete healing. CONCLUSIONS: and CLINICAL IMPLICATIONS: Despite complex anatomy and diagnoses of DI and open apexes, both patients successfully underwent nonsurgical endodontic treatment involving the use of a collagen membrane and an MTA apical plug. Using an extraradicular barrier clinically can help improve the adaptation of MTA in the apexes of open-apex teeth to achieve a complete seal. PMID- 22298556 TI - The effect of smoking on the bioavailability of metronidazole in plasma and saliva. AB - BACKGROUND: Cigarette smoking is considered to be a major risk factor for periodontal disease, and the antimicrobial agent metronidazole is commonly used for treatment of periodontitis. The authors evaluated the effect of cigarette smoking on the bioavailability of metronidazole in plasma and saliva. METHODS: Thirteen smokers and 13 nonsmokers received a single oral dose of 750 milligrams of metronidazole. Study personnel collected blood and saliva samples at baseline and at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24 and 48 hours after metronidazole administration. The authors quantified plasmatic and salivary metronidazole concentrations by means of high-performance liquid chromatography, and they determined the pharmacokinetic parameters and analyzed them statistically by using the Mann-Whitney test and nonpaired t test (alpha = 5 percent). RESULTS: The authors detected a significant reduction in plasmatic metronidazole concentrations in smokers at 1 hour, 1.5 hours and 2 hours compared with nonsmokers (P < .05). They also found a significant reduction in the maximum concentration in plasma in smokers as compared with that of nonsmokers (P < .05). The authors observed no statistically significant differences in the salivary concentration or pharmacokinetics between the two groups, however (P > .05). CONCLUSION: Cigarette smoking interfered with the bioavailability of metronidazole in plasma but not in saliva. Practice Implications. The clinical significance of these findings needs to be investigated further to verify the effectiveness of metronidazole in smokers. PMID- 22298557 TI - Repair or replacement of defective direct resin-based composite restorations: contemporary teaching in U.S. and Canadian dental schools. AB - BACKGROUND: Opportunities exist to promote minimally invasive dentistry by repairing rather than replacing defective and failing direct resin-based composite restorations. The authors conducted a study to investigate the current teaching of such techniques in U.S. and Canadian dental schools. METHODS: In late 2010, the authors, with the assistance of the Consortium of Operative Dentistry Educators, invited 67 U.S. and Canadian dental schools to participate in an Internet-based survey. RESULTS: The response rate was 72 percent. Eighty-eight percent of the dental schools taught repair of defective direct resin-based composite restorations. Of these schools, 79 percent reported providing both didactic and clinical teaching. CONCLUSIONS: Although teaching repair of defective resin-based composite restorations was included in the didactic curricula of most schools, students in some schools did not gain experience in minimally invasive management of defective resin-based composite restorations by means of performing repair procedures. The American Dental Association's Code on Dental Procedures and Nomenclature does not have a procedure code for resin-based composite restoration repairs, which may limit patients' access to this dental treatment. CLINICAL IMPLICATIONS: Teaching dental students minimally invasive dentistry procedures, including restoration repair, extends the longevity of dental restorations and reduces detrimental effects on teeth induced by invasive procedures, thereby serving the interests of patients. PMID- 22298558 TI - Isolation of Staphylococcus aureus from environmental surfaces in an academic dental clinic. AB - BACKGROUND: Staphylococcus aureus is an important health care-associated pathogen that often is resistant to antibiotics. The authors conducted a pilot study to determine if abiotic surfaces in a dental clinic were contaminated frequently. METHODS: The authors sampled surfaces with swabs that they then used to inoculate selective and differential media. CHRO-Magar Staph aureus (DRG International, Mountainside, N.J.) was the most effective. They used phenotypic and genotypic tests to identify presumptive S. aureus colonies. They determined the sensitivity of S. aureus isolates to five antibiotics, including oxacillin, according to the Kirby-Bauer method. RESULTS: The authors recovered S. aureus from 20 of 429 surfaces (4.7 percent). Most isolates were resistant to penicillin but none were resistant to the other antibiotics. No isolate carried the mecA gene encoding resistance to methicillin. The authors considered one site to be highly contaminated (> 200 colony-forming units [CFUs]), but all other sites that tested positive yielded fewer than 5 CFUs. CONCLUSIONS: Abiotic surfaces in the authors' dental clinic were not a reservoir for methicillin-resistant S. aureus. The authors identified and eliminated one nonclinical site of potential methicillin sensitive S. aureus cross-contamination. CLINICAL IMPLICATIONS: Periodic sampling of surfaces for S. aureus may be a useful adjunct to standard infection control practices in dental health care settings. PMID- 22298559 TI - Prevalence of bisphosphonate-related osteonecrosis in patients with cancer could be as high as 13.3 percent. AB - SYSTEMATIC REVIEW CONCLUSION: The overall mean weighted prevalence of bisphosphonate-related osteonecrosis (BON) in the evaluated studies was 6.1 percent, and the overall weighted prevalence of BON in studies with documented follow-up was 13.3 percent. CRITICAL SUMMARY ASSESSMENT: There is inconsistency in prevalence study results and a lack of studies in which investigators have evaluated quality-of-life issues related to or the economic effects of BON in patients with cancer. PMID- 22298560 TI - How to manage the behavior of patients who disregard scheduled appointment times. PMID- 22298561 TI - What ethical considerations are involved when a patient requests recommendations for a new general dentist from a specialist? PMID- 22298562 TI - The global history of rabies and the historian's gaze: an essay review. AB - In reviewing three recent books on the history of rabies (hydrophobia), this essay explores ways in which historians can frame, or figure, global histories of this ancient and still-dreaded disease, focusing especially on problems of place, time, and agency. PMID- 22298563 TI - "Spitting is dangerous, indecent, and against the law!" legislating health behavior during the American tuberculosis crusade. AB - Tuberculosis was the leading cause of death in early twentieth-century America. Reducing the sputum vector of contagion by changing public behavior initially focused on anti-spitting campaigns. According to most Progressive Era health experts, "promiscuous" spitting was a prime culprit in spreading the disease. Beginning in 1896 in New York, towns and cities throughout America passed anti spitting legislation, sometimes creating tensions between individual liberty and the need to protect public health, and often highlighting class issues. Progressives viewed anti-spitting legislation in a favorable light because they advocated improving the health and well-being of Americans using state-of-the-art medical knowledge and because they often advocated the use of law and the coercive power of the state to impose order on society. PMID- 22298564 TI - Use of quality indicators in patient care: a senior primary care physician trying to take good care of his patients. AB - Dr A is a senior primary care physician who recently moved from a small private practice to a larger group-model practice. He believes he was able to provide higher-quality and more individualized care for his patients in his small practice. As Dr A has discovered, quality measurement and improvement activities in primary care have evolved from a focus on an individual patient in an examination room to a systems approach that incorporates population management. Although many frustrations remain with physicians' ability to measure and influence the quality of care received by populations of patients, quality measures and monitoring have improved and should continue to improve. However, the perspective of patients and experienced physicians like Dr A also should be incorporated into quality measurement and management systems. Dr A clearly has the welfare of his patients at heart, and his experience and perspective could help improve his organization's systems of care and identify resources to deliver the best care. PMID- 22298565 TI - A system for coreference resolution for the clinical narrative. AB - OBJECTIVE: To research computational methods for coreference resolution in the clinical narrative and build a system implementing the best methods. METHODS: The Ontology Development and Information Extraction corpus annotated for coreference relations consists of 7214 coreferential markables, forming 5992 pairs and 1304 chains. We trained classifiers with semantic, syntactic, and surface features pruned by feature selection. For the three system components--for the resolution of relative pronouns, personal pronouns, and noun phrases--we experimented with support vector machines with linear and radial basis function (RBF) kernels, decision trees, and perceptrons. Evaluation of algorithms and varied feature sets was performed using standard metrics. RESULTS: The best performing combination is support vector machines with an RBF kernel and all features (MUC score=0.352, B(3)=0.690, CEAF=0.486, BLANC=0.596) outperforming a traditional decision tree baseline. DISCUSSION: The application showed good performance similar to performance on general English text. The main error source was sentence distances exceeding a window of 10 sentences between markables. A possible solution to this problem is hinted at by the fact that coreferent markables sometimes occurred in predictable (although distant) note sections. Another system limitation is failure to fully utilize synonymy and ontological knowledge. Future work will investigate additional ways to incorporate syntactic features into the coreference problem. CONCLUSION: We investigated computational methods for coreference resolution in the clinical narrative. The best methods are released as modules of the open source Clinical Text Analysis and Knowledge Extraction System and Ontology Development and Information Extraction platforms. PMID- 22298566 TI - Multidimensional evaluation of a radio frequency identification wi-fi location tracking system in an acute-care hospital setting. AB - Real-time locating systems (RTLS) have the potential to enhance healthcare systems through the live tracking of assets, patients and staff. This study evaluated a commercially available RTLS system deployed in a clinical setting, with three objectives: (1) assessment of the location accuracy of the technology in a clinical setting; (2) assessment of the value of asset tracking to staff; and (3) assessment of threshold monitoring applications developed for patient tracking and inventory control. Simulated daily activities were monitored by RTLS and compared with direct research team observations. Staff surveys and interviews concerning the system's effectiveness and accuracy were also conducted and analyzed. The study showed only modest location accuracy, and mixed reactions in staff interviews. These findings reveal that the technology needs to be refined further for better specific location accuracy before full-scale implementation can be recommended. PMID- 22298567 TI - A simple heuristic for blindfolded record linkage. AB - OBJECTIVES: To address the challenge of balancing privacy with the need to create cross-site research registry records on individual patients, while matching the data for a given patient as he or she moves between participating sites. To evaluate the strategy of generating anonymous identifiers based on real identifiers in such a way that the chances of a shared patient being accurately identified were maximized, and the chances of incorrectly joining two records belonging to different people were minimized. METHODS: Our hypothesis was that most variation in names occurs after the first two letters, and that date of birth is highly reliable, so a single match variable consisting of a hashed string built from the first two letters of the patient's first and last names plus their date of birth would have the desired characteristics. We compared and contrasted the match algorithm characteristics (rate of false positive v. rate of false negative) for our chosen variable against both Social Security Numbers and full names. RESULTS: In a data set of 19 000 records, a derived match variable consisting of a 2-character prefix from both first and last names combined with date of birth has a 97% sensitivity; by contrast, an anonymized identifier based on the patient's full names and date of birth has a sensitivity of only 87% and SSN has sensitivity 86%. CONCLUSION: The approach we describe is most useful in situations where privacy policies preclude the full exchange of the identifiers required by more sophisticated and sensitive linkage algorithms. For data sets of sufficiently high quality this effective approach, while producing a lower rate of matching than more complex algorithms, has the merit of being easy to explain to institutional review boards, adheres to the minimum necessary rule of the HIPAA privacy rule, and is faster and less cumbersome to implement than a full probabilistic linkage. PMID- 22298568 TI - Oral tocotrienols are transported to human tissues and delay the progression of the model for end-stage liver disease score in patients. AB - The natural vitamin E family is composed of 8 members equally divided into 2 classes: tocopherols (TCP) and tocotrienols (TE). A growing body of evidence suggests TE possess potent biological activity not shared by TCP. The primary objective of this work was to determine the concentrations of TE (200 mg mixed TE, b.i.d.) and TCP [200 mg alpha-TCP, b.i.d.)] in vital tissues and organs of adults receiving oral supplementation. Eighty participants were studied. Skin and blood vitamin E concentrations were determined from healthy participants following 12 wk of oral supplementation of TE or TCP. Vital organ vitamin E levels were determined by HPLC in adipose, brain, cardiac muscle, and liver of surgical patients following oral TE or TCP supplementation (mean duration, 20 wk; range, 1-96 wk). Oral supplementation of TE significantly increased the TE tissue concentrations in blood, skin, adipose, brain, cardiac muscle, and liver over time. alpha-TE was delivered to human brain at a concentration reported to be neuroprotective in experimental models of stroke. In prospective liver transplantation patients, oral TE lowered the model for end-stage liver disease (MELD) score in 50% of patients supplemented, whereas only 20% of TCP supplemented patients demonstrated a reduction in MELD score. This work provides, to our knowledge, the first evidence demonstrating that orally supplemented TE are transported to vital organs of adult humans. The findings of this study, in the context of the current literature, lay the foundation for Phase II clinical trials testing the efficacy of TE against stroke and end-stage liver disease in humans. PMID- 22298569 TI - Consumption of breads containing in situ-produced arabinoxylan oligosaccharides alters gastrointestinal effects in healthy volunteers. AB - Arabinoxylan oligosaccharides (AXOS) are studied as food compounds with prebiotic potential. Here, the impact of consumption of breads with in situ-produced AXOS on intestinal fermentation and overall gastrointestinal characteristics was evaluated in a completely randomized, double-blind, controlled, cross-over study. Twenty-seven healthy volunteers consumed 180 g of wheat/rye bread with or without in situ-produced AXOS (WR(+) and WR(-), respectively) daily for 3 wk. Consumption of WR(+) corresponded to an AXOS intake of ~2.14 g/d. Refined wheat flour bread without AXOS (W(-)) (180 g/d) was provided during the 3-wk run-in and wash-out periods. At the end of each treatment period, participants collected urine for 48 h as well as a feces sample. Additionally, all participants completed a questionnaire about stool characteristics and gastrointestinal symptoms during the last week of each period. Urinary phenol and p-cresol excretions were significantly lower after WR(+) intake compared to WR(-). Consumption of WR(+) significantly increased fecal total SCFA concentrations compared to intake of W( ). The effect of WR(+) intake was most pronounced on butyrate, with levels 70% higher than after consumption of W(-) in the run-in or wash-out period. Consumption of WR(+) tended to selectively increase the fecal levels of bifidobacteria (P = 0.06) relative to consumption of W(-). Stool frequency increased significantly after intake of WR(+) compared to WR(-). In conclusion, consumption of breads with in situ-produced AXOS may favorably modulate intestinal fermentation and overall gastrointestinal properties in healthy humans. PMID- 22298570 TI - Vision changes after spaceflight are related to alterations in folate- and vitamin B-12-dependent one-carbon metabolism. AB - Approximately 20% (7 of 38) of astronauts on International Space Station (ISS) missions have developed measurable ophthalmic changes after flight. This study was conducted to determine if the folate- and vitamin B-12-dependent 1-carbon metabolic pathway is altered in these individuals. Since 2006, we have conducted experiments on the ISS to evaluate nutritional status and related biochemical indices of astronauts before, during, and after flight. Data were modeled to evaluate differences between individuals with ophthalmic changes (n = 5) and those without them (n = 15), all of whom were on ISS missions of 48-215 d. We also determined whether mean preflight serum concentrations of the 1-carbon metabolites and changes in measured cycloplegic refraction after flight were associated. Serum homocysteine (Hcy), cystathionine, 2-methylcitric acid (2MCA), and methylmalonic acid concentrations were 25-45% higher (P < 0.001) in astronauts with ophthalmic changes than in those without them. These differences existed before, during, and after flight. Preflight serum concentrations of Hcy and cystathionine, and mean in-flight serum folate, were correlated with change (postflight relative to preflight) values in refraction (P < 0.05), and preflight serum concentrations of 2MCA tended to be associated (P = 0.06) with ophthalmic changes. The biochemical differences observed in crewmembers with vision issues strongly suggest that their folate- and vitamin B-12-dependent 1-carbon transfer metabolism was affected before and during flight. The consistent differences in markers of 1-carbon metabolism between those who did and those who did not develop changes in vision suggest that polymorphisms in enzymes of this pathway may interact with microgravity to cause these pathophysiologic changes. PMID- 22298571 TI - Prenatal micronutrient supplements cumulatively increase fetal growth. AB - Prenatal multiple micronutrients (UNIMMAP) improve fetal growth only moderately compared to iron and folic acid alone (IFA). Whether this is due to insufficient amounts of UNIMMAP or to IFA being in reality an active control is unknown. We assessed the association between cumulative micronutrient intake (CMI) and fetal growth by secondary analysis of a randomized controlled trial in Burkina Faso where tablet intake was directly observed. We applied 2-part residual regression models adjusted for main confounders. Among the 1056 single pregnancies included, the mean CMI (+/- SD) was 124 +/- 54 tablets. The odds of delivering a small-for gestational-age baby was reduced by 21% [(95%CI: 5, 35); P = 0.013] for each additional tertile of CMI. The association between CMI and birth weight was positively modified by gestational age at enrollment (P-interaction = 0.001). Each unit of CMI was associated with a 1.6-g [(95%CI: 0.3, 3.1); P = 0.019] higher birth weight at a mean-centered gestational age at enrollment, with a higher gradient observed later in pregnancy. Maternal BMI at enrollment was also a positive modifying factor (P-interaction = 0.02), with no association of CMI with birth weight for low BMI. There was no evidence of an effect modification by group allocation; i.e., we observed the same change in birth weight per unit of CMI with either IFA or UNIMMAP. Yet UNIMMAP increased birth weight by 69 g [(95%CI: 58, 81); P < 0.001] relative to IFA. We found similar results for thoracic and cephalic circumferences. In conclusion, for both IFA and UNIMMAP, the effect on fetal growth is cumulative. The supplementation should therefore begin as early as possible in pregnancy, even if the growth increment per CMI is higher in late than in early pregnancy. Women with a low BMI should also receive extra energy. PMID- 22298572 TI - Stable iron isotope studies in Rwandese women indicate that the common bean has limited potential as a vehicle for iron biofortification. AB - Biofortification of plants is a new approach to combat iron deficiency. Common beans (Phaseolus vulgaris) can be bred with a higher iron concentration but are rich in iron absorption inhibitors, phytic acid (PA), and polyphenols (PP). To evaluate the potential of beans to combat iron deficiency, three iron absorption studies were carried out in 61 Rwandese women with low iron status. Studies 1 and 2 compared iron absorption from high and low PP beans, similar in PA and iron, fed as bean puree in a double meal design or with rice and potatoes as multiple meals. Study 3 compared iron absorption from high and normal iron beans with similar PP levels and a PA:iron molar ratio, fed with potatoes or rice in multiple meals. Iron absorption was measured as erythrocyte incorporation of stable iron isotopes. In study 1, iron absorption from the high PP bean (3.4%) was 27% lower (P < 0.01) than from low PP bean (4.7%), but when fed in multiple meals (study 2), there was no difference (7 and 7.4%, respectively; P > 0.05). In study 3, iron absorption from the high iron bean (3.8%) was 40% lower (P < 0.001) than from the normal iron bean (6.3%), resulting in equal amounts of iron absorbed. When beans were combined with other meal components in multiple meals, high PP concentration had no negative impact on iron absorption. However, the quantity of iron absorbed from composite meals with high iron beans was no higher than with normal iron beans, indicating that efficacious iron biofortification may be difficult to achieve in beans rich in PA and PP. PMID- 22298573 TI - Isoleucine and leucine independently regulate mTOR signaling and protein synthesis in MAC-T cells and bovine mammary tissue slices. AB - Understanding the regulatory effects of individual amino acids (AA) on milk protein synthesis rates is important for improving protein and AA requirement models for lactation. The objective of this study was to examine the effects of individual essential AA (EAA) on cellular signaling and fractional protein synthesis rates (FSR) in bovine mammary cells. Omission of L-arginine, L isoleucine, L-leucine, or all EAA reduced (P < 0.05) mammalian target of rapamycin (mTOR; Ser2448) and ribosomal protein S6 (rpS6; Ser235/236) phosphorylation in MAC-T cells. Phosphorylation of mTOR and rpS6 kinase 1 (S6K1; Thr389) decreased (P < 0.05) in the absence of L-isoleucine, L-leucine, or all EAA in lactogenic mammary tissue slices. Omission of L-tryptophan also reduced S6K1 phosphorylation (P = 0.01). Supplementation of L-leucine to media depleted of EAA increased mTOR and rpS6 and decreased eukaryotic elongation factor 2 (Thr56) phosphorylation (P < 0.05) in MAC-T cells. Supplementation of L isoleucine increased mTOR, S6K1, and rpS6 phosphorylation (P < 0.05). No single EAA considerably affected eukaryotic initiation factor 2-alpha (eIF2alpha; Ser51) phosphorylation, but phosphorylation was reduced in response to provision of all EAA (P < 0.04). FSR declined when L-isoleucine (P = 0.01), L-leucine (P = 0.01), L-methionine (P = 0.02), or L-threonine (P = 0.07) was depleted in media and was positively correlated (R = 0.64, P < 0.01) with phosphorylation of mTOR and negatively correlated (R = -0.42, P = 0.01) with phosphorylation of eIF2alpha. Such regulation of protein synthesis will result in variable efficiency of transfer of absorbed EAA to milk protein and is incompatible with the assumption that a single nutrient limits protein synthesis that is encoded in current diet formulation strategies. PMID- 22298574 TI - A comparison of micronutrient inadequacy and risk of high micronutrient intakes among vitamin and mineral supplement users and nonusers in Canada. AB - Although supplement use is prevalent in North America, there is little information on how supplements affect the prevalence of nutrient adequacy or risk of intakes greater than the tolerable upper intake level (UL). The objectives of this study were to compare the prevalence of nutrient adequacy and percent of intakes greater than the UL from diet alone between supplement users and nonusers and determine the contribution of supplements to nutrient intakes. Dietary intakes (24-h recall) and supplement use (previous 30 d) from respondents >=1 y in the Canadian Community Health Survey 2.2 (n = 34,381) were used to estimate the prevalence of nutrient adequacy and intakes greater than the UL. Software for Intake Distribution Evaluation was used to estimate usual intakes. The prevalence of nutrient adequacy from diet alone was not significantly higher among supplement users than nonusers for any nutrient. Based on diet alone, children 1 13 y had a low prevalence of nutrient adequacy (<30%) except for vitamin D and calcium. Among respondents >=14 y, inadequacies of vitamins A and D, calcium, and magnesium were >30%. For other nutrients, there was a low prevalence of nutrient adequacy. There were no nutrient intakes greater than the UL from diet alone, except zinc in children. When supplements were included, >=10% of users in some age/sex groups had intakes of vitamins A and C, niacin, folic acid, iron, zinc, and magnesium greater than the UL, reaching >80% for vitamin A and niacin in children. In conclusion, from diet alone, the prevalence of nutrient adequacy was low for most nutrients except for calcium, magnesium, and vitamins A and D. For most nutrients, supplement users were not at greater risk of inadequacy than nonusers; supplement use sometimes led to intakes greater than the UL. PMID- 22298575 TI - Adult immunization 2012: politics, process, and progress. PMID- 22298576 TI - Recommended adult immunization schedule: United States, 2012. PMID- 22298578 TI - The future of health technology assessment. PMID- 22298579 TI - Measuring health-related quality of life: new findings and new questions. PMID- 22298580 TI - Effects of benzodiazepine receptor ligands on simultaneous visual discriminations of variable difficulty. AB - Benzodiazepine receptor (BZR) ligands have been demonstrated to affect the performance in tasks measuring attentional abilities. In such tasks, subjects typically are required to discriminate visual and/or auditory stimuli. The possibility that the effects of BZR ligands on the performance in tasks measuring attention are primarily due to effects on discriminative processes has not been tested systematically. Rats were trained to discriminate between simultaneously presented pairs of visual stimuli flashing either at 5 Hz versus 4.17, 3.75, 2.5, 1.67 or 1.25 Hz (group 1; FAST), or at 1.25, 1.46, 1.67, 2.5 or 3.33 Hz versus 5 Hz (group 2; SLOW) for 4.8 s (20 trials per discrimination type; sequence of pairs was randomized). In both groups, response accuracy depended significantly on the discriminability of the stimuli, with near perfect accuracy in response to most different pairs of stimuli and near chance-level accuracy in response to least different pairs of stimuli. Administration of the BZR full agonist chlordiazepoxide (1.56, 6.25, 9.38 mg/kg; i.p.) potently increased the number of errors of omission which, following the higher doses, confounded the effects on absolute numbers of correct and incorrect responses. However, the available data do not suggest that the agonist affected the animals' abilities to discriminate between the stimuli. Similarly, administration of the BZR ligands ZK 93 426 and MDL 26,479 (which negatively modulate GABAergic transmission) produced no systematic effects. These data suggest that the effects of BZR ligands on the performance in tasks measuring attentional abilities are not primarily due to effects on the animals' ability to discriminate sensory stimuli. PMID- 22298581 TI - Differences between three rat strains in sensitivity to prepulse inhibition of an acoustic startle response: influence of apomorphine and phencyclidine pretreatment. AB - In the present study we have examined the effect of varying three prepulse parameters (prepulse intensity, prepulse duration, prepulse-pulse interval) on the level of prepulse inhibition (PPI) in Lister hooded, Wistar and Sprague Dawley rats. The results indicate that each strain showed subtle differences in sensitivity to the prepulse. For instance, Sprague-Dawley and Lister hooded rats showed PPI to prepulses of lower saliency compared to Wistar rats. Optimal prepulse parameters were selected for each strain to examine the effects of apomorphine and phencyclidine on PPI. Further inter-strain differences were noted; apomorphine (0.1-1 mg/kg) increased startle amplitude in Lister hooded and Sprague-Dawley, but not Wistar rats. PPI was attenuated in each strain by apomorphine pretreatment. In a final series of experiments, phencyclidine disrupted PPI in each strain, although with greater potency in the Lister hooded rats. A marked behavioural syndrome was seen at phencyclidine doses that disrupted PPI. It is concluded that rat strain and prepulse parameters are important variables in studying drug effects on PPI. PMID- 22298582 TI - The effects of serotonergic drugs on short-term spatial memory in rats. AB - The effects of modulating the serotonergic system on short-term spatial memory were investigated using delayed matching to position and delayed non-matching to position procedures. Rats were trained on one of the two tasks until stability and then administered the drugs 30 min before a session. Fluoxetine (0.625-10 mg/kg), a serotonin uptake inhibitor, fenfluramine (0.313-5 mg/kg), a serotonin release enhancer, and ipsapirone (2.5-10 mg/kg), a serotonin 1A partial agonist, were all injected subcutaneously in saline solution. Apart from fenfluramine, none of the compounds affected accuracy in either procedure, but some effects on other non- mnemonic measures were seen. At 5 mg/kg, fenfluramine significantly affected latency to respond, total responses on the levers and nosepokes in the foodtray as well as accuracy, indicating a non-specific disruption of behaviour rather than a selective effect on memory processes. These data suggest that cognitive effects of serotonergic drugs are difficult to identify in normal animals, irrespective of the mechanism of action of the drug. These data conflict with recent reports indicating memory-enhancing effects of serotonin uptake inhibitors. PMID- 22298583 TI - Effects of chlormethiazole on psychological performance under conditions of constant plasma concentrations. AB - Chlormethiazole was administered intravenously to six healthy volunteers (four male, two female, aged 20-33 years) using a loading dose followed by a maintenance infusion lasting ~ 90 min. Doses were individually calculated from previous pharmacokinetic investigations in these subjects to produce a target steady-state plasma concentration of 1.5 MUg ml(-1). Effects of chlormethiazole were determined using a short battery consisting of digit-symbol substitution, body sway and visual analogue scales, which was performed repeatedly before, during and after the active infusion. A more comprehensive battery of performance tests was performed once before and once during the active infusion. The mean plasma concentration of chlormethiazole obtained was 1.33 MUg ml(-1). This produced marked sedation, with subjects scoring themselves as much more drowsy on chlormethiazole than on placebo, and global impairment to performance. An analysis of the slopes of scores on the performance tests in the short battery showed no evidence of a diminution of the effects of chlormethiazole over the infusion period. The same was true of the majority of the visual analogue scales, but two scales, rating eye symptoms and nose symptoms, did decline over the period of the infusion. Recovery was rapid, subjects returning to approximately baseline levels of performance within 30 min of discontinuation of the infusion. These results suggest that acute tolerance to the CNS effects of chlormethiazole does not occur over this time scale, but is found for peripheral effects such as eye and nose symptoms. PMID- 22298584 TI - 5-HT 2C receptor sensitivity during treatment with selective serotonin re-uptake inhibitors. AB - We studied the effect of repeated treatment with selective serotonin re-uptake inhibitors (SSRIs) on the sensitivity of brain 5-HT(2C) receptors, by measuring the decrease in slow wave sleep (SWS) that follows administration of meta chlorophenylpiperazine (mCPP) (7.5 mg orally). mCPP significantly lowered SWS both in patients taking SSRIs and in a group of healthy controls. There was, however, no difference in the response between the two groups. The results do not support the suggestion that repeated SSRI treatment alters the sensitivity of 5 HT(2C) receptors in the human brain. The present study, however, cannot exclude the possibility that a decrease in 5-HT(2C) receptor sensitivity was offset by higher plasma levels of mCPP in the SSRI-treated group. PMID- 22298585 TI - A double-blind comparison of sertraline and clomipramine in the treatment of major depressive disorder and associated anxiety in general practice. AB - In this double-blind study in primary care patients, the efficacy and safety of sertraline, an antidepressant which is a selective inhibitor of serotonin re uptake, was compared with clomipramine. Patients with DSM-III-defined major depression and with significant anxiety randomly received 50-150 mg of either sertraline (N=51) or clomipramine (N=55) once daily for 6 weeks. The mean final daily dose was 63.5 mg sertraline and 60.6 mg clomipramine. Seventy five percent of sertraline-treated and 79% of clomipramine-treated patients were maintained on the lowest dose of 50 mg once daily. The mean scores of all the rating scales (HAM-D, HAM-A, HAD, CGI) showed similar efficacy between the treatments in reducing the symptoms of depression and anxiety. Clomipramine was less well tolerated than sertraline with a greater overall incidence of side effects, or significantly greater incidence of anticholinergic side effects and significantly more patient withdrawals due to side effects; 18% in the clomipramine group compared with 4% in the sertraline group. The results indicate that sertraline is an effective agent to use in primary care patients with depression and associated symptoms of anxiety and is better tolerated than the tricyclic comparator clomipramine. PMID- 22298586 TI - Is there a distinct subtype of major depression in the elderly? AB - Evidence for and against the notion of a specific subtype of depressive illness in the elderly is reviewed. There is little to support a distinction based on clinical features, neurobiological markers, treatment response or prognosis, but subtle organic cerebral change may predispose to late-onset depression in a significant minority of cases. PMID- 22298587 TI - Pimozide treatment of a male case with de Clerambault's syndrome and schizophrenia. AB - Effective treatment with pimozide of a male patient with secondary de Clerambault's syndrome (DCS) and schizophrenia is reported. There was no evidence of relapse at 24-month follow-up. Pimozide is suggested to be the drug of choice in DCS and may be in other disorders in which symptoms of erotomania are prominent. The unique anti-erotomanic activity of pimozide may be due to its calcium channel antagonist activity, a property which is not shared by the other antipsychotic drugs. PMID- 22298588 TI - The association of fluoxetine with seizures. PMID- 22298589 TI - Paradoxical acute anxiety exacerbation with alpidem in a panic disorder patient. PMID- 22298590 TI - Towards the incorporation of lumbar puncture into clinical trials for multiple sclerosis. PMID- 22298591 TI - National estimate of multiple sclerosis incidence in France (2001-2007). AB - BACKGROUND: In France, the incidence of multiple sclerosis (MS) is not well known, and MS is one of the 30 long-term illnesses for which patients are covered for 100% of their health care costs. OBJECTIVE: To estimate the incidence of MS in France and its geographic variations. METHODS: We estimated the national rate for notification of MS to the main French health insurance system, and its confidence interval (CI), between November 2000 and October 2007, which covers 87% of the population. We analysed geographic variations using a Bayesian approach. RESULTS: Between November 2000 and October 2007, among a covered population of 52,449,871, some 28,682 individuals were registered as having MS. After age standardization according to the European population, the notification rate for MS was 6.8 per 100,000 (6.7-6.9), 9.8 (9.7-10.0) in women and 3.7 (3.6 3.8) in men. When the under-notification rate (11.5% and 29%) was taken into account, the notification rate per 100,000 inhabitants was estimated between 7.6 and 8.8. The notification rate was higher in north-eastern France, and lower on the Atlantic coast and in the Alps as well as on both sides of the Rhone River. CONCLUSIONS: This study, conducted on a representative French population, provides for the first time national estimates of MS incidence between November 2000 and October 2007. PMID- 22298593 TI - The dark side of E2F1: in transit beyond apoptosis. AB - E2F1 plays a critical role in cell-cycle progression and the induction of apoptosis in response to DNA damage. The latest evidence has uncovered that this tumor suppressor is most relevant for cancer progression and chemoresistance. Increased abundance of E2F1 triggers invasion and metastasis by activating growth receptor signaling pathways, which in turn promote an antiapoptotic tumor environment. The data shed light on the molecular mechanisms underlying E2F1 induced prometastatic activity and predict its radical switch from a mediator of cell death toward an accelerator of tumor progression. This raises the perspective of new drug targets at late-stage cancer. PMID- 22298594 TI - Cancer stem cells: distinct entities or dynamically regulated phenotypes? AB - The origins of tumor-propagating neoplastic stem-like cells [cancer stem cells (CSC)] and their relationship to the bulk population of tumor cells that lack stem-like tumor-propagating features (i.e., transit-amplifying cancer progenitor cells) remain unclear. Recent findings from multiple laboratories show that cancer progenitor cells have the capacity to dedifferentiate and acquire a stem like phenotype in response to either genetic manipulation or environmental cues. These findings suggest that CSCs and relatively differentiated progenitors coexist in dynamic equilibrium and are subject to bidirectional conversion. In this review, we discuss emerging concepts regarding the stem-like phenotype, its acquisition by cancer progenitor cells, and the molecular mechanisms involved. Understanding the dynamic equilibrium between CSCs and cancer progenitor cells is critical for the development of therapeutic strategies to deplete tumors of their tumor-propagating and treatment-resistant cell subpopulations. PMID- 22298595 TI - Sef downregulation by Ras causes MEK1/2 to become aberrantly nuclear localized leading to polyploidy and neoplastic transformation. AB - Subcellular trafficking of key oncogenic signal pathway components is likely to be crucial for neoplastic transformation, but little is known about how such trafficking processes are spatially controlled. In this study, we show how Ras activation causes aberrant nuclear localization of phosphorylated mitogen activated protein (MAP)/extracellular signal-regulated kinase (ERK; MEK) MEK1/2 to drive neoplastic transformation. Phosphorylated MEK1/2 was aberrantly located within the nucleus of primary colorectal tumors and human colon cancer cells, and oncogenic activation of Ras was sufficient to induce nuclear accumulation of phosphorylated MEK1/2 and ERK1/2 in intestinal epithelial cells. Enforced nuclear localization of MEK1 in epithelial cells or fibroblasts was sufficient for hyperactivation of ERK1/2, thereby driving cell proliferation, chromosomal polyploidy, and tumorigenesis. Notably, Ras-induced nuclear accumulation of activated MEK1/2 was reliant on downregulation of the spatial regulator Sef, the reexpression of which was sufficient to restore normal MEK1/2 localization and a reversal of Ras-induced proliferation and tumorigenesis. Taken together, our findings indicate that Ras-induced downregulation of Sef is an early oncogenic event that contributes to genetic instability and tumor progression by sustaining nuclear ERK1/2 signaling. PMID- 22298596 TI - Sphingosine-1-phosphate produced by sphingosine kinase 1 promotes breast cancer progression by stimulating angiogenesis and lymphangiogenesis. AB - Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid mediator that promotes breast cancer progression by diverse mechanisms that remain somewhat unclear. Here we report pharmacologic evidence of a critical role for sphingosine kinase 1 (SphK1) in producing S1P and mediating tumor-induced hemangiogenesis and lymphangiogenesis in a murine model of breast cancer metastasis. S1P levels increased both in the tumor and the circulation. In agreement, serum S1P levels were significantly elevated in stage IIIA human breast cancer patients, compared with age/ethnicity-matched healthy volunteers. However, treatment with the specific SphK1 inhibitor SK1-I suppressed S1P levels, reduced metastases to lymph nodes and lungs, and decreased overall tumor burden of our murine model. Both S1P and angiopoietin 2 (Ang2) stimulated hemangiogenesis and lymphangiogenesis in vitro, whereas SK1-I inhibited each process. We quantified both processes in vivo from the same specimen by combining directed in vivo angiogenesis assays with fluorescence-activated cell sorting, thereby confirming the results obtained in vitro. Notably, SK1-I decreased both processes not only at the primary tumor but also in lymph nodes, with peritumoral lymphatic vessel density reduced in SK1-I treated animals. Taken together, our findings show that SphK1-produced S1P is a crucial mediator of breast cancer-induced hemangiogenesis and lymphangiogenesis. Our results implicate SphK1 along with S1P as therapeutic targets in breast cancer. PMID- 22298597 TI - Tumor-initiating cells in childhood neuroblastoma--letter. PMID- 22298599 TI - The role of mannitol as a nephroprotectant in patients receiving cisplatin therapy. AB - OBJECTIVE: To review the efficacy and safety of concomitant mannitol administration with cisplatin therapy to reduce the incidence of nephrotoxicity. DATA SOURCES: A literature search was performed via MEDLINE, PubMed, and the Cochrane Library (1945-August 2011) using the terms mannitol, cisplatin, nephrotoxicity, and forced diuresis. Reference citations from the publications identified were also reviewed. STUDY SELECTION AND DATA EXTRACTION: The search was limited to studies conducted in humans. All studies in which mannitol was used for forced diuresis with cisplatin therapy were evaluated. DATA SYNTHESIS: Cisplatin therapy can lead to transient and permanent renal impairment. Molecular and histologic changes occur in the renal tubules, which contribute to nephrotoxicity. The adverse effect profile of cisplatin is well documented, but the prevention strategies to alleviate renal impairment due to treatment are less understood. Mannitol plus hydration has been used for several years to alleviate toxicity associated with cisplatin therapy. However, the data for mannitol administration have not been convincing. When the use of mannitol and hydration is compared directly to hydration alone, mannitol shows no benefit. In some patients, not only was mannitol not protective, its administration was associated with worsening renal function. CONCLUSIONS: Although mannitol plus hydration is used to decrease cisplatin-induced nephrotoxicity, there are no compelling data that the addition of mannitol is more nephroprotective than the use of hydration alone. Appropriate hydration remains the most reasonable strategy to reduce the incidence of cisplatin-induced nephrotoxicity. PMID- 22298600 TI - Comparison of the effects of energy drink versus caffeine supplementation on indices of 24-hour ambulatory blood pressure. AB - BACKGROUND: Cardiovascular events associated with energy drink consumption have been reported, but few data exist to delineate the hemodynamic effects of energy drinks. OBJECTIVE: To compare the effects of an energy drink versus caffeine supplementation on blood pressure (BP) indices as measured by 24-hour ambulatory BP monitoring (ABPM). METHODS: Healthy, nonsmoking, normotensive volunteers (aged 18-45 years) taking no medications were enrolled in a single-center, open-label, 2-period crossover pilot study. During each study period, subjects received either an energy drink (Red Bull Energy Drink, each dose containing 80 mg of caffeine and 1000 mg of taurine in an 8.3-oz serving) or a control (compounded caffeine solution, each dose containing 80 mg of caffeine solution in 8 oz of bottled water) at 0800, 1100, 1500, and 1900 hours and underwent 24-hour ABPM. The study periods were separated by a washout period (4-30 days). Mean 24-hour, daytime, and nighttime systolic (SBP), diastolic (DBP), and mean arterial (MAP) BP; BP load; and percent nocturnal dipping were compared between study periods. RESULTS: Nine subjects (5 females, mean [SD] age 27.7 [5.0] years) completed the study. Mean 24-hour SBP (123.2 vs 117.4 mm Hg, p = 0.04), DBP (73.6 vs 68.2 mm Hg, p = 0.02), and MAP (90.1 vs 84.8 mm Hg, p = 0.03) were significantly higher during energy drink supplementation versus caffeine supplementation. Daytime DBP (77.0 vs 72.0 mm Hg, p = 0.04) also was significantly higher with the energy drink versus caffeine supplementation. Trends in higher daytime SBP (127.0 vs 121.9 mm Hg, p = 0.05) and MAP (93.6 vs 88.6 mm Hg, p = 0.05) were recorded with energy drink supplementation versus caffeine supplementation. Nighttime SBP and DBP loads were significantly higher with the energy drink, but nocturnal dipping did not differ significantly between study periods. CONCLUSIONS: Single-day energy drink supplementation increased mean 24-hour and daytime BP compared to caffeine control in this pilot study. Additional research is warranted to better understand the hemodynamic effects of energy drink consumption. PMID- 22298601 TI - Gabapentin enacarbil for treatment of restless legs syndrome in adults. AB - OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, precautions, dosing recommendations, and patient counseling for gabapentin enacarbil for the treatment of restless legs syndrome (RLS) in adults. DATA SOURCES: A literature search was conducted using the terms gabapentin enacarbil, XP13512/GSK1838262, and restless legs syndrome. MEDLINE, Books@Ovid, Journals@Ovid Full Text, BIOSIS Previews, and EMED databases were the primary search sites (2004-October 2011). All English-based articles and abstracts obtained from the literature searches were reviewed. Additional information was obtained from references cited in the articles. STUDY SELECTION AND DATA EXTRACTION: All gabapentin enacarbil information related to RLS was considered. Study selection included human trials evaluating safety and efficacy of gabapentin enacarbil for the treatment of RLS. DATA SYNTHESIS: Gabapentin enacarbil is a prodrug of gabapentin that is Food and Drug Administration (FDA) approved for the treatment of moderate-to-severe primary RLS in adults. In placebo-controlled trials, gabapentin enacarbil demonstrated efficacy in reducing the symptoms of RLS. Most clinical trials assessed gabapentin enacarbil at dosages greater than the FDA-approved 600-mg dosage. For the approved dose of 600 mg, the most commonly reported adverse effects are somnolence and dizziness. CONCLUSIONS: Clinical trials have evaluated gabapentin enacarbil for safety and efficacy in treating moderate-to-severe RLS symptoms for up to 64 weeks. It offers a pharmacokinetic advantage over gabapentin by having improved absorption and a longer duration of action, but clinically significant differences are yet to be determined. Potential disadvantages of gabapentin enacarbil include cost, concerns of suicide risk and pancreatic cancer, and a lack of data for the FDA approved 600-mg dosage. Overall, gabapentin enacarbil is a viable therapeutic option for adults with moderate-to-severe RLS for whom more conventional therapies have failed. PMID- 22298602 TI - Tesamorelin: a growth hormone-releasing factor analogue for HIV-associated lipodystrophy. AB - OBJECTIVE: To evaluate the efficacy and safety of tesamorelin, a growth hormone releasing factor analogue approved by the Food and Drug Administration in November 2010 for the treatment of lipodystrophy associated with HIV infection. DATA SOURCES: Literature was obtained through MEDLINE (1948-November 2011) and International Pharmaceutical Abstracts (1970-October 2011) using the search terms tesamorelin, TH9507, growth hormone releasing factor, and HIV-associated lipodystrophy syndrome. Additional publications were obtained through review of references within primary literature publications as well as pertinent Web sites. STUDY SELECTION AND DATA EXTRACTION: All articles published in English identified from the data sources were evaluated and all pertinent information was included. All studies relevant to the evaluation of efficacy and safety of tesamorelin in the management of HIV-associated lipodystrophy were included, with a focus on trials completed in humans. DATA SYNTHESIS: In 2 Phase 3 clinical trials and their pooled analyses, tesamorelin was proven to significantly decrease waist circumference and visceral adipose tissue (VAT) following 26 weeks of treatment. Both trials also demonstrated significant improvements in some subjective body image parameters. Both studies had 26-week extension phases that confirmed maintenance of VAT improvements on treatment without adverse impact on blood glucose and lipid parameters. Limited data support off-label uses of tesamorelin at this time. CONCLUSIONS: Tesamorelin is effective in improving visceral adiposity and body image in patients with HIV-associated lipodystrophy over 26-52 weeks of treatment. Potential limitations for its use include high cost and lack of long-term safety and adherence data. Tesamorelin provides a useful treatment option for management of patients with significant lipodystrophy related to HIV infection. PMID- 22298603 TI - Obstetrical opportunities: will pharmacy ever realize them? AB - Based on a survey of the American College of Clinical Pharmacy Women's Health Practice and Research Network and our own experience, the pharmacy profession has limited involvement in obstetric pharmacotherapy. We believe that such involvement in pregnancies with complicated conditions can result in significant improvement of pregnancy outcomes. Moreover, we believe this involvement would be welcomed by the physicians caring for these patients. This commentary documents current obstetrical pharmacy practices and proposes changes for the profession of pharmacy to consider. PMID- 22298604 TI - Serum potassium influencing interacting drugs: risk-modifying strategies also needed at discontinuation. AB - BACKGROUND: Although the discontinuation of a medication may have important clinical consequences, there is generally much less attention given to medication surveillance when a drug is stopped than when it is started. OBJECTIVE: To investigate the consequences on serum potassium levels of discontinuing a drug that increases the serum potassium level (PID?) and a drug that decreases the serum potassium level (PLD?) in patients taking both. METHODS: Patients who were hospitalized in the University Medical Centre Utrecht in 2004-2009 and were using both a PID? and a PLD? were included when one of these drugs was discontinued during hospitalization. Serum potassium levels measured before (potassium(1)) and after (potassium(2)) discontinuation were compared in patients who stopped the PLD? and in patients who stopped the PID?. RESULTS: In the group of patients who stopped the PLD? (ie, continued the PID?), mean serum potassium levels increased 0.19 mEq/L (range -0.9 to 1.8 mEq/L). After discontinuation of the PLD?, serum potassium levels increased in 91 (59%) patients. Five patients (3.2%) developed hyperkalemia (potassium(2) >5.5 mEq/L). In the group of patients who stopped the PID? (ie, continued the PLD?), mean serum potassium levels decreased 0.40 mEq/L (range -2.6 to 0.7 mEq/L). Serum potassium levels decreased in 61 (70%) patients after discontinuation of the PID?. Fifteen patients (17%) developed hypokalemia (potassium(2) <3.5 mEq/L). Results were not influenced by length of stay, age, sex, renal function, and type of medication discontinued. CONCLUSIONS: The effects of serum potassium-influencing drugs need to be monitored not only after starting but also after stopping the medication. The same may hold true for the effects of other drugs. Clinical risk management should therefore focus on the risks not only when new medication is prescribed, but also when medication is stopped. PMID- 22298606 TI - Rosiglitazone, myocardial ischemic risk, and recent regulatory actions. AB - OBJECTIVE: To review the evidence surrounding rosiglitazone and ischemic cardiovascular risk and discuss the Food and Drug Administration (FDA) decision to revise safety information and restrict access to the drug. DATA SOURCES: A literature search was conducted through MEDLINE (1950-January 2012), PubMed (1966 January 2012), and International Pharmaceutical Abstracts (1970-December 2011) using the search terms rosiglitazone and cardiovascular risk. Regulatory documents from the FDA and the Center for Drug Evaluation and Research, as well as reference citations from publications identified, were reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles in English identified from the data sources were evaluated for inclusion. DATA SYNTHESIS: Literature regarding rosiglitazone and ischemic cardiovascular risk has shown inconsistent results. Meta-analyses by the FDA, GlaxoSmithKline, and several independent research groups suggest an increased risk for myocardial infarction (MI), while others have not. Long-term, controlled trials not designed to evaluate cardiovascular outcomes did not find a significant increase in cardiovascular events and had low event rates overall. The RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes in Oral Agent Combination Therapy for Type 2 Diabetes) trial is the only prospective randomized trial to date designed to evaluate cardiovascular outcomes of rosiglitazone; the results were limited because of issues with study design and event adjudication. The only direct comparisons between rosiglitazone and pioglitazone are observational studies in which pioglitazone had a more favorable MI risk profile. CONCLUSIONS: Data involving rosiglitazone and an association with ischemic cardiovascular risk have yielded variable results. The FDA made the decision to restrict access to rosiglitazone in September 2010 by requiring GlaxoSmithKline to submit a risk evaluation and mitigation strategy (REMS). Drug labeling was revised in February 2011, and the rosiglitazone REMS program took full effect in November 2011. PMID- 22298608 TI - Pulmonary vascular responses to exercise: a haemodynamic observation. PMID- 22298609 TI - Seeking the right targets: gene therapy advances in pulmonary arterial hypertension. PMID- 22298610 TI - Rhinoviruses: markers of, or causative for, recurrent wheeze and asthma? PMID- 22298611 TI - Alveolar epithelial type II cells from embryonic stem cells: knights in shining armour? PMID- 22298612 TI - Silent gastro-oesophageal reflux and microaspiration in IPF: mounting evidence for anti-reflux therapy? PMID- 22298613 TI - Low-dose methotrexate in PAH related to T-cell large granular lymphocyte leukaemia. PMID- 22298614 TI - Congenital rubella syndrome and left pulmonary artery sling. PMID- 22298615 TI - Effects of fasudil in patients with high-altitude pulmonary hypertension. PMID- 22298616 TI - Nuclear magnetic resonance-based metabolomics of exhaled breath condensate: methodological aspects. PMID- 22298617 TI - Metabolomic signatures in nuclear magnetic resonance spectra of exhaled breath condensate identify asthma. PMID- 22298618 TI - Widespread use of serological tests for tuberculosis: data from 22 high-burden countries. PMID- 22298619 TI - Palliative percutaneous cryoablation in a patient with locally advanced invasive thymoma. PMID- 22298620 TI - Supported home-care schemes: the key to increasing outpatient care? PMID- 22298621 TI - Community acquired pneumonia: severity scores as an adjunct to clinical judgement. PMID- 22298622 TI - Supported home-care schemes: the key to increasing outpatient care? PMID- 22298624 TI - Putting the 'A' in atypical: does alpha2-adrenoceptor antagonism account for the therapeutic advantage of new antipsychotics? PMID- 22298625 TI - Differential changes in glutamate receptor subunit messenger RNAs in rat brain after haloperidol treatment. AB - Glutamate receptors are implicated in several neuropsychiatric disorders and in the actions of neuroleptic drugs used to treat them. To help clarify how these drugs impinge upon the glutamatergic system, we have studied the effects of 2 weeks' haloperidol (2 mg kg(-1) d(-1)) upon the distribution and abundance of glutamate receptor mRNAs in rat brain. The mRNAs detected were those encoding the glutamate-binding protein (GBP), the N-methyl D-aspartate (NMDA) receptor (NR1 subunit) and the flip and flop isoforms of alpha-amino-3-hydroxy- 5-methyl-4 isoxazolpropionate (AMPA)-preferring non-NMDA receptors gluR1 and gluR2. The mRNAs were studied using in situ hybridization histochemistry in dorsolateral striatum, nucleus accumbens, frontal cortex and hippocampus. Haloperidol led to an increase in GBP mRNA in striatum and frontal cortex but not in hippocampus. AMPA receptor mRNAs showed gene- and isoform-specific alterations in treated animals, with a significant increase in the proportion of gluR2 flip compared to gluR2 flop. The gluR1 flop:gluR2 flop ratio also increased. No differences were observed for NR1 mRNA in any area. Thus, subchronic administration of haloperidol has a molecularly and spatially specific effect upon expression of glutamate receptor-related transcripts. The data have several implications. Firstly, the enhanced expression of GBP mRNA may contribute to the alterations in other glutamatergic parameters observed after neuroleptics. Secondly, the pattern of changes for the NMDA and AMPA receptor mRNAs suggests that the alterations in density of these receptors and their mRNAs reported in schizophrenia are not an artefact of neuroleptic treatment. Finally, the specific increase in flip:flop mRNA ratio for gluR2, together with the increased proportion of gluR1 flop:gluR2 flop mRNA, is likely to affect the properties of the encoded AMPA receptors. Such changes may be relevant to the desired or undesired effects of these drugs. PMID- 22298626 TI - L-dopa helps positive but not negative features of neuroleptic-insensitive chronic schizophrenia. AB - L-dopa (Sinemet-110 in a final dose equivalent to - 4 g per day) added to maintenance chlorpromazine, produced a small antipsychotic effect in a group of eight severely impaired male chronic schizophrenic in-patients. Negative symptoms were unaffected by L-dopa, although the improvement in psychotic behaviour and positive symptoms was restricted to the four patients with the most severe negative symptoms measured during the control treatment period. These L-dopa responders also tended to improve slightly when the dose of chlorpromazine was halved, an indication of their poor, or even counter-therapeutic response to conventional neuroleptic medication given in relatively high dosage. Signs of increased dopaminergic activity (raised eye blink rate and reduced plasma prolactin) were not observed in subjects showing an antipsychotic response to L dopa. This raises the possibility that L-dopa may exert an antipsychotic effect in neuroleptic-insensitive subjects by altering noradrenergic activity in the brain. PMID- 22298627 TI - Assessment of the dependence potential of the potent high-efficacy 5-HT1A agonist S-14506 in rats. AB - This study assessed the dependence potential of S-14506 [ 1- [ 2-(4 fluorobenzoylamino)ethyl]-4-(7-methoxy napthyl) piperazine], a novel, potent 5 HT(1A) full agonist with anxiolytic and antidepressant actions in animal models. The dependence potential of S-14506 was compared with that of the benzodiazepine (BZ) chlordiazepoxide (CDP). BZ withdrawal caused weight loss, aphagia and hyperthermia after chronic b.i.d. treatment for 21 days. None of these withdrawal effects were seen after similar b.i.d. S-14506 treatment at high doses. However, the acute pharmacological actions of CDP and S-14506 differed on a number of indices. Specifically, CDP increased food intake and body weight, whilst S-14506 decreased these measures, possibly due to the induction of the serotonin syndrome. Of particular interest was the observation that S-14506 induced marked hypothermia, to which complete tolerance developed very rapidly (after only 1 day). The observation of marked, rapid tolerance to S-14506-induced hypothermia, in conjunction with the absence of withdrawal hyperthermia after prolonged chronic treatment at high doses, suggests that tolerance to this effect of S 14506 can be dissociated from dependence. Collectively, the data reported suggest that the full 5-HT(1A) agonist S-14506 is devoid of dependence potential, other human and animal studies having previously suggested that partial 5-HT(1A) agonists typically induce no, or minimal, dependence. PMID- 22298628 TI - On the mechanism(s) of morphine-induced hypothermia. AB - The effects of morphine on core body temperature of mice in the presence or absence of catecholamine receptor antagonists were examined. Administration of different doses of morphine (20, 30 and 40 mg/kg) to mice caused a hypothermic effect. Pre-treatment of animals with the opioid receptor antagonist naloxone (1, 1.5 and 3 mg/kg), the D-2 receptor antagonists sulpiride (25 and 50 mg/kg), pimozide (0.0625, 0.125 and 0.25 mg/kg) and the adenosine receptor antagonist theophylline (25 and 50 mg/kg) decreased the morphine-induced hypothermia. The D 1 receptor antagonist SCH 23390 (0.1 and 0.2 mg/kg), the peripheral D-2 antagonist domperidone (10 and 30 mg/kg), the serotonin (5-HT) antagonist methysergide (5 and 10 mg/kg), the adrenoceptor antagonist phenoxybenzamine (2.5 and 5 mg/kg) and the beta-adrenoceptor antagonist propranolol (5 and 10 mg/kg) did not inhibit the morphine response. The antimuscarinic drug atropine (5 and 10 mg/kg) caused a slight decrease in the morphine response. In animals pre-treated with reserpine (5 mg/kg), a hyperthermic response was observed after morphine injection. It is concluded that indirect dopaminergic or adenosine receptor mechanism(s) may be involved in the morphine-induced hypothermia in mice. PMID- 22298629 TI - Anti-conflict effect of 5-HT1A agonists in rats: a new model for evaluating anxiolytic-like activity. AB - A new conflict procedure was developed to study the potential anti-punishment effects of 5-HT( 1A) agonists as compared to diazepam. In this paradigm, the opportunity existed for rats to choose during punished periods between immediate, punished reinforcement and delayed, non-punished reinforcement. The results confirm that, for non-sedative doses (1 mg/kg), diazepam increases the number of punished responses. Furthermore, the present paradigm seems sensitive for the detection of 5-HT(1A) activity. Buspirone, gepirone, ipsapirone, zalospirone and 8-OH-DPAT increased responding for immediate but punished reinforcement. 1-(2 pyrimidinyl)piperazine, the common metabolite of the azapirones, does not participate in their anti-conflict effect. NAN 190, a 5-HT(1A) antagonist, was shown to block the 5-HT(1A) agonists. The findings of the present study suggest that benzodiazepines and 5-HT( 1A) agonists reduce the capacity to tolerate delays in reward. Abnormality in serotonin systems may be associated with poor impulse control. PMID- 22298630 TI - The efficacy of selective serotonin re-uptake inhibitors in depression: a meta analysis of studies against tricyclic antidepressants. AB - A meta-analysis of the efficacy of five selective serotonin re-uptake inhibitors (SSRIs) against non-selective and noradrenergic re-uptake inhibitors (mainly tricyclic antidepressants, TCAs) is presented. Fifty five double- blind studies were identified after excluding those multiply reported or with methodological problems likely to bias the outcome in favour of SSRIs. Standardised effect sizes and 95% confidence intervals were calculated based on the difference in the reduction in mean Hamilton depression rating scale (HDRS) scores for the two antidepressants. For studies not reporting standard deviations, the pooled variance from complete studies was used and a variance-weighted mean effect size calculated. There were no differences in efficacy between SSRIs and comparator antidepressants for SSRIs taken together or individually. If studies were classified into high and low depression scores based on a median split of initial HDRS scores, there was a slight advantage to TCAs in the high HDRS group. In addition, SSRIs were slightly less effective than TCAs in in-patients and against combined serotonin and noradrenaline re-uptake inhibitors (clomipramine and amitriptyline). These findings were accounted for by a clinically significant lower efficacy of paroxetine in these subgroups. In contrast, SSRIs as a group were marginally more effective than noradrenergic antidepressants, a finding accounted for by two studies with sertraline. Fluvoxamine was the only SSRI to have been tested adequately in in-patients, where it displayed equal efficacy to TCAs. This meta-analysis confirms that SSRIs and TCAs are in general equally effective, but suggests that paroxetine's efficacy in in-patients and against clomipramine and amitriptyline is not proven. PMID- 22298631 TI - BAP/SKB Young Psychopharmacologist Award Towards a neuroendocrinology of obsessive-compulsive disorder. AB - Neuroendocrine research has made an important contribution to the understanding of psychiatric illness in vivo. This review is a summary of the recent neuroendocrine studies on obsessive-compulsive disorder (OCD) patients carried out at the Departments of Psychiatry at Trinity College Medical School and St. Patrick's Hospital, Dublin, Ireland. We found that both serotonergic and cholinergic abnormalities were present in OCD, while noradrenergic responsivity and hypothalmic-pituitary axis function were normal. The data suggests that OCD may have a unique neuroendocrinology. PMID- 22298632 TI - Dyskinesias following treatment with 5-HT re-uptake inhibitors. AB - Three cases of dyskinesia attributable to selective serotonergic antidepressant drugs are presented. The patients were not on other medication nor had they been in preceding weeks. The movement disorder disappeared on cessation of the drug within a time period corresponding to the expected wash-out for the different preparations. The emergence of dyskinesic symptoms coincided with a significant deterioration in mental state after an initial good response to the particular medication. Considering the apparently selective action of the serotonin re uptake inhibitors, these cases suggest that movement disorders and psychiatric symptoms are unlikely to be due to single neurotransmitter mechanisms and that a disturbance of the balance between the different systems is a more likely hypothesis. PMID- 22298633 TI - Hypersalivation and lithium toxicity. PMID- 22298634 TI - Improvement of abnormal saccadic eye movements in Huntington's disease by sulpiride: a case study. AB - Sulpiride treatment improved both the abnormal asymmetric saccadic eye movements (SEM) and the abnormal involuntary movements (AIMs) in a patient with Huntington's disease (HD). However, sulpiride corrected the abnormalities of SEM in the right, but not the left, hemi-field and the degeneration of the left striatal tissue was greater as visualised by the magnetic resonance imaging (MRI) scan. PMID- 22298636 TI - The foundation of the British Association for Psychopharmacology. PMID- 22298635 TI - Tolerability of combined treatment with lithium and paroxetine: 19 cases treated under open conditions. AB - Nineteen patients resistant to paroxetine monotherapy were treated by lithium augmentation for 6 weeks to assess tolerability. Although the addition of lithium increased the number of adverse events, none were serious. The combination of lithium and paroxetine is safe enough to warrant further investigation as a treatment for resistant depression. PMID- 22298637 TI - Urinary albumin excretion in heart failure with preserved ejection fraction: an interim analysis of the CHART 2 study. AB - AIMS: Heart failure with preserved ejection fraction (HFpEF) is characterized by multiple co-morbidities, including chronic kidney disease that is one of the prognostic risks for these patients. This study was performed to evaluate the value of determination of albuminuria using a urine dipstick test (UDT), combined with estimated glomerular filtration rate (eGFR), for predicition of mortality in HFpEF. METHODS AND RESULTS: We enrolled 2465 consecutive patients with overt HF with EF >=50% in our Chronic Heart Failure Analysis and Registry in the Tohoku District 2 (CHART-2) study (NCT00418041). We defined trace or more UDT as positive. We divided the patients into the following four groups based on eGFR and UDT; group 1 (G1) (eGFR >=60, negative UDT), G2 (eGFR >=60, positive UDT), G3 (eGFR <60, negative UDT), and G4 (eGFR <60, positive UDT). In total, 29.5% of the HFpEF patients had a positive UDT. HFpEF patients with a positive UDT were characterized by higher brain natriuretic peptide levels and frequent histories of hypertension or diabetes. During a mean follow-up of 2.5 years, HFpEF patients with a positive UDT showed higher mortality in each stratum of eGFR levels. A multivariable adjusted Cox model showed that when compared with G1 (reference), the hazard ratio of all-cause death for G2, G3, and G4 was 2.44 (95% confidence interval 1.47-4.05, P=0.001), 1.43 (0.92-2.23, P=0.12), and 2.71 (1.72-4.27, P<0.001), respectively. Furthermore, the prognostic value of a positive UDT was robust for both cardiovascular and non-cardiovascular deaths. CONCLUSIONS: These results indicate that measurement of albuminuria in addition to eGFR is useful for appropriate risk stratification in HFpEF patients. PMID- 22298638 TI - Serum microRNA profiling and breast cancer risk: the use of miR-484/191 as endogenous controls. AB - It has been demonstrated that there are abundant stable microRNAs (miRNAs) in plasma/serum, which can be detected and are potentially disease specific. However, the lack of suitable endogenous controls for serum miRNA detection is the restriction for the widely usage of this kind of biomarkers and for the between-laboratory comparison of the findings. We first systematically screened for endogenous control miRNAs (ECMs) by testing 10 pooling samples (using both Solexa sequencing and TaqMan low density array) and 50 individual samples (using quantitative reverse transcription-PCR) of different cancer traits and healthy controls. Then we assessed serum miRNAs used as potential biomarkers for breast cancer risk prediction based on a two-stage case-control analysis, including 48 breast cancer patients and 48 controls for the discovery stage and 76 breast cancer patients and 76 controls for validation. We identified two candidate ECMs (miRNA-191 and miRNA-484). Normalized by the two ECMs, we found four miRNAs (miR 16, miR-25, miR-222 and miR-324-3p) that were consistently differentially expressed between breast cancer cases and controls. The area under the receiver operating characteristic curve is 0.954 for the four-miRNA signature in the discovery stage (sensitivity = 0.917 and specificity = 0.896) and 0.928 in the validation stage (sensitivity = 0.921 and specificity = 0.934). In conclusion, the four-miRNA signature from serum may serve as a non-invasive prediction biomarker for breast cancer. Furthermore, we proposed the combination of miRNA 484 and miRNA-191 as endogenous control for serum miRNA detection, at least for most common cancers. PMID- 22298639 TI - Transcriptional regulation of miR-196b by ETS2 in gastric cancer cells. AB - E26 transformation-specific sequence (ETS)-2 is a transcriptional modulator located on chromosome 21, alterations in its expression have been implicated with a reduced incidence of solid tumors in Down syndrome patients. MicroRNAs (miRNAs) are thought to participate in diverse biological functions; however, the regulation of miRNAs is not well characterized. Recently, we reported that miR 196b is highly expressed in gastric cancers. Herein, we demonstrate that miR-196b expression was significantly repressed by ETS2 during gastric cancer oncogenesis. We demonstrate that knockdown of endogenous ETS2 expression increases miR-196b expression. A genomic region between -751 and -824 bp upstream of the miR-196b transcriptional start site was found to be critical for the repression activity. This putative regulatory promoter region contains three potential ETS2-binding motifs. Mutations within the ETS2 binding sites blocked the repression activity of ETS2. Furthermore, knockdown of ETS2 or overexpression of miR-196b significantly induced migration and invasion in gastric cancer cells. In addition, alterations in ETS2 and miR-196b expression in gastric cancer cell lines affected the expression of epithelial-mesenchymal transition-related genes. The levels of vimentin, matrix metalloproteinase (MMP)-2 and MMP9 were drastically induced, but levels of E-cadherin were decreased in shETS2- or miR 196b-transfected cells. Our data indicate that ETS2 plays a key role in controlling the expression of miR-196b, and miR-196b may mediate the tumor suppressor effects of ETS2. We demonstrated that miR-196b was transcriptionally regulated by ETS2 and there was an inverse expression profile between miR-196b and ETS2 in clinical samples. This finding could be beneficial for the development of effective cancer diagnostic and alternative therapeutic strategies. PMID- 22298640 TI - Urinary levels of volatile organic carcinogen and toxicant biomarkers in relation to lung cancer development in smokers. AB - Besides polycyclic aromatic hydrocarbons (PAH) and 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone (NNK), which are established lung carcinogens, tobacco smoke also contains relatively large quantities of volatile organic carcinogens and toxicants, including 1,3-butadiene, ethylene oxide, benzene, acrolein and crotonaldehyde. Although animal experiments showed that some of these compounds can induce tumors in multiple organs including the lung, epidemiological studies of their relationship with lung cancer in smokers have not been reported. Therefore, in this study, we quantified urinary mercapturic acid metabolites of 1,3-butadiene, ethylene oxide, benzene, acrolein and crotonaldehyde in addition to urinary biomarkers for PAH, NNK and nicotine in 343 lung cancer cases and 392 matched controls among a cohort of 18,244 Chinese men in Shanghai, China, followed from 1986 to 2006. Compared with the lowest quartiles, highest quartiles of all measured mercapturic acids were associated with statistically significantly ~2-fold increased risk for lung cancer (all P's for trend <0.01) after adjustment for smoking intensity and duration. The positive associations between biomarkers of ethylene oxide, benzene or acrolein and lung cancer risk remained statistically significant after adjustment for biomarkers of PAH and NNK, whereas urinary total cotinine completely explained the mercapturic acid metabolites and lung cancer associations (all P's for trend >= 0.39). We conclude that mercapturic acid metabolites of 1,3-butadiene, ethylene oxide, benzene, acrolein and crotonaldehyde may not be independent risk predictors of lung cancer among Shanghai smokers, in contrast to biomarkers of PAH, NNK and nicotine exposure. PMID- 22298641 TI - Curcumin inhibits protein phosphatases 2A and 5, leading to activation of mitogen activated protein kinases and death in tumor cells. AB - Curcumin can induce p53-independent apoptosis. However, the underlying mechanism remains to be defined. Here, we show that curcumin-induced apoptosis in a panel of tumor cells with mutant p53. Curcumin rapidly induced activation of the mitogen-activated protein kinases (MAPKs) including extracellular signal regulated kinase 1/2 (Erk1/2) and c-Jun N-terminal kinase (JNK). Inhibition of JNK (with SP600125) or Erk1/2 (with U0126) partially prevented curcumin-induced cell death in the cells. Similarly, expression of dominant negative c-Jun or downregulation of Erk1/2 in part attenuated curcumin-induced cell death. It appears that curcumin-induced activation of MAPKs and apoptosis was due to induction of reactive oxygen species (ROS), as pretreatment with N-acetyl-L cysteine, a ROS scavenger, blocked these events. Furthermore, we found that curcumin-induced activation of MAPK pathways was related to inhibition of the serine/threonine protein phosphatases 2A (PP2A) and 5 (PP5). Overexpression of PP2A or PP5 partially prevented curcumin-induced activation of JNK and Erk1/2 phosphorylation as well as cell death. The results suggest that curcumin induction of ROS activates MAPKs, at least partially by inhibiting PP2A and PP5, thereby leading to p53-independent apoptosis in tumor cells. PMID- 22298642 TI - Receptor activator of nuclear factor-kappaB ligand is a novel inducer of myocardial inflammation. AB - AIMS: Although increased levels of myocardial receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) have been reported in heart failure, the role of this pathway in mediating activation of inflammatory pathways during myocardial remodelling is less well understood. This study sought to determine the role of myocardial RANKL in regulating cytokine expression. METHODS AND RESULTS: A marked increase in RANKL expression occurred as early as 6h following transverse aortic constriction (TAC) in mouse hearts and persisted at 3 and 17 days. An increase in tumour necrosis factor-alpha (TNF-alpha), interleukin (IL) 1alpha, and IL-1beta was observed in the hypertrophied hearts only at 3 or 17 days after TAC. Treatment with losartan significantly attenuated TAC-induced cardiac hypertrophy, in parallel with decreased expression of RANKL, TNF-alpha, IL-1alpha, and IL-1beta. Furthermore, injection of a RANKL-neutralizing monoclonal antibody attenuated RANKL-induced cytokine expression. RANKL stimulated expression of TNF-alpha, IL-1alpha, and IL-1beta in neonatal rat cardiomyocytes via activation of NF-kappaB. RANKL-induced NF-kappaB activation and expression of these cytokines were both attenuated when RANK, receptor for RANKL, or TRAF2 or TRAF6, adaptors for RANK, was silenced by siRNA. Furthermore, inhibitors of phospholipase C (PLC), protein kinase C (PKC), and inhibitor of kappaB kinase also significantly inhibited RANKL-induced cellular activities, but inhibitors of phosphatidylinositol 3-kinase, extracellular signal-regulated kinase, or p38 mitogen-activated protein kinase were without effect. CONCLUSION: Our data demonstrate for the first time that the pressure-overloaded myocardium generates RANKL, which induces TNF-alpha, IL-1alpha, and IL-1beta production via a RANK-TRAF2/TRAF6-PLC-PKC-NF-kappaB-mediated autocrine mechanism. PMID- 22298643 TI - The GRAF family member oligophrenin1 is a RhoGAP with BAR domain and regulates Rho GTPases in platelets. AB - AIMS: Platelet adhesion and aggregation is essential for haemostasis and thrombosis. Cytoskeletal reorganization of activated platelets plays a crucial role in these processes and implies activation of Rho GTPases. Rho GTPases are regulated by GTPase-activating proteins (GAPs) that stimulate GTP hydrolysis to terminate Rho signalling. In this study, we explored the regulation of Rho GTPases in platelets. METHODS AND RESULTS: Oligophrenin1 (OPHN1) is a RhoGAP regulating cytoplasmic protein that has been investigated in patients with X linked mental retardation. Here, we identified OPHN1 in mouse platelets where it co-localizes to actin-rich regions and Rho GTPases. OPHN1 exhibits strong GTPase stimulating activity towards RhoA, Cdc42, and Rac1 and regulates cell adhesion and spreading. Furthermore, OPHN1 controls RhoA-mediated stress fibre and focal adhesion formation as well as filopodia and lamellipodia development. The analysis of different domains of OPHN1 revealed distinct functions in Rho hydrolysis. The C-terminus of OPHN1 displays an essential unit for Rho regulation, whereas the PH domain is a regulatory unit of OPHN1 controlling GAP function. The N-terminal BAR (Bin/amphiphysin/Rvs)-like domain is involved in GAP regulation but not in cytoskeleton rearrangements or Rho regulation and acts as a guidance domain to direct this GAP to its substrate. CONCLUSION: Our results suggest that OPHN1 is a powerful regulator of Rho GTPase activity in platelets that is critical for the reorganization of the cytoskeleton, which is a major process required for stable platelet adhesion and thrombus formation to occur. PMID- 22298644 TI - The demise of nursing? PMID- 22298645 TI - 'There is only narrative': using case studies in nursing ethics. PMID- 22298646 TI - Stress of conscience among staff caring for older persons in Finland. AB - Caring for older persons is both rewarding and consuming. Work with older people in Finland has been shown to be more burdensome than in the other Nordic countries. The aim of this study was to try out a Finnish version of the Stress of Conscience Questionnaire (SCQ) and explore stress of conscience in staff caring for older persons in Finland. The data were collected from the nursing staff (n = 350) working with older people in health centre wards, municipal and private nursing homes, and municipal and private dementia care units in Finland. It emerged clearly from the results that Finnish nursing staff mostly felt that they did not have enough time to provide good care to patients, and this gave them a troubled conscience. They also felt that the demanding work taxed their energy, a consequence being that they could not give their own families and loved ones the attention they would have liked. PMID- 22298647 TI - Refusal of treatment and decision-making capacity. AB - This article explores refusal of medical treatment by adult patients from ethical and legal perspectives. Initially, consequentialist and deontological ethical theory are outlined. The concepts of autonomy, paternalism and competence are described and an overview of Beauchamp and Childress's principle-based approach to moral reasoning is given. Relevant common law is discussed and the provisions of the Mental Capacity Act 2005 in assessing competence is evaluated. In order to demonstrate the consideration of moral issues in clinical practice, ethical theory is applied to two well-known incidents: the case of Re MB, where doubt over decision-making capacity led to a paternalistic act to override a patient's choice; and the death of Emma Gough, a situation where respect for autonomy prevailed when healthcare staff acted lawfully in following a patient's refusal of life-saving treatment. Finally, guidance from regulatory bodies on the roles and responsibilities of health professionals in relation to this topic are considered. PMID- 22298650 TI - Cellular and molecular specificity of pituitary gland physiology. AB - The anterior pituitary gland has the ability to respond to complex signals derived from central and peripheral systems. Perception of these signals and their integration are mediated by cell interactions and cross-talk of multiple signaling transduction pathways and transcriptional regulatory networks that cooperate for hormone secretion, cell plasticity, and ultimately specific pituitary responses that are essential for an appropriate physiological response. We discuss the physiopathological and molecular mechanisms related to this integrative regulatory system of the anterior pituitary gland and how it contributes to modulate the gland functions and impacts on body homeostasis. PMID- 22298652 TI - Controlling the stem cell compartment and regeneration in vivo: the role of pluripotency pathways. AB - Since the realization that embryonic stem cells are maintained in a pluripotent state through the interplay of a number of key signal transduction pathways, it is becoming increasingly clear that stemness and pluripotency are defined by the complex molecular convergence of these pathways. Perhaps this has most clearly been demonstrated by the capacity to induce pluripotency in differentiated cell types, so termed iPS cells. We are therefore building an understanding of how cells may be maintained in a pluripotent state, and how we may manipulate cells to drive them between committed and pluripotent compartments. However, it is less clear how cells normally pass in and out of the stem cell compartment under normal and diseased physiological states in vivo, and indeed, how important these pathways are in these settings. It is also clear that there is a potential "dark side" to manipulating the stem cell compartment, as deregulation of somatic stem cells is being increasingly implicated in carcinogenesis and the generation of "cancer stem cells." This review explores these relationships, with a particular focus on the role played by key molecular regulators of stemness in tissue repair, and the possibility that a better understanding of this control may open the door to novel repair strategies in vivo. The successful development of such strategies has the potential to replace or augment intervention-based strategies (cell replacement therapies), although it is clear they must be developed with a full understanding of how such approaches might also influence tumorigenesis. PMID- 22298651 TI - Molecular mechanism of pancreatic and salivary gland fluid and HCO3 secretion. AB - Fluid and HCO(3)(-) secretion is a vital function of all epithelia and is required for the survival of the tissue. Aberrant fluid and HCO(3)(-) secretion is associated with many epithelial diseases, such as cystic fibrosis, pancreatitis, Sjogren's syndrome, and other epithelial inflammatory and autoimmune diseases. Significant progress has been made over the last 20 years in our understanding of epithelial fluid and HCO(3)(-) secretion, in particular by secretory glands. Fluid and HCO(3)(-) secretion by secretory glands is a two-step process. Acinar cells secrete isotonic fluid in which the major salt is NaCl. Subsequently, the duct modifies the volume and electrolyte composition of the fluid to absorb the Cl(-) and secrete HCO(3)(-). The relative volume secreted by acinar and duct cells and modification of electrolyte composition of the secreted fluids varies among secretory glands to meet their physiological functions. In the pancreas, acinar cells secrete a small amount of NaCl-rich fluid, while the duct absorbs the Cl(-) and secretes HCO(3)(-) and the bulk of the fluid in the pancreatic juice. Fluid secretion appears to be driven by active HCO(3)(-) secretion. In the salivary glands, acinar cells secrete the bulk of the fluid in the saliva that is driven by active Cl(-) secretion and contains high concentrations of Na(+) and Cl(-). The salivary glands duct absorbs both the Na(+) and Cl(-) and secretes K(+) and HCO(3)(-). In this review, we focus on the molecular mechanism of fluid and HCO(3)(-) secretion by the pancreas and salivary glands, to highlight the similarities of the fundamental mechanisms of acinar and duct cell functions, and to point out the differences to meet gland-specific secretions. PMID- 22298655 TI - Physical activity and exercise in the regulation of human adipose tissue physiology. AB - Physical activity and exercise are key components of energy expenditure and therefore of energy balance. Changes in energy balance alter fat mass. It is therefore reasonable to ask: What are the links between physical activity and adipose tissue function? There are many complexities. Physical activity is a multifaceted behavior of which exercise is just one component. Physical activity influences adipose tissue both acutely and in the longer term. A single bout of exercise stimulates adipose tissue blood flow and fat mobilization, resulting in delivery of fatty acids to skeletal muscles at a rate well-matched to metabolic requirements, except perhaps in vigorous intensity exercise. The stimuli include adrenergic and other circulating factors. There is a period following an exercise bout when fatty acids are directed away from adipose tissue to other tissues such as skeletal muscle, reducing dietary fat storage in adipose. With chronic exercise (training), there are changes in adipose tissue physiology, particularly an enhanced fat mobilization during acute exercise. It is difficult, however, to distinguish chronic "structural" changes from those associated with the last exercise bout. In addition, it is difficult to distinguish between the effects of training per se and negative energy balance. Epidemiological observations support the idea that physically active people have relatively low fat mass, and intervention studies tend to show that exercise training reduces fat mass. A much discussed effect of exercise versus calorie restriction in preferentially reducing visceral fat is not borne out by meta-analyses. We conclude that, in addition to the regulation of fat mass, physical activity may contribute to metabolic health through beneficial dynamic changes within adipose tissue in response to each activity bout. PMID- 22298653 TI - Epoxides and soluble epoxide hydrolase in cardiovascular physiology. AB - Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites that importantly contribute to vascular and cardiac physiology. The contribution of EETs to vascular and cardiac function is further influenced by soluble epoxide hydrolase (sEH) that degrades EETs to diols. Vascular actions of EETs include dilation and angiogenesis. EETs also decrease inflammation and platelet aggregation and in general act to maintain vascular homeostasis. Myocyte contraction and increased coronary blood flow are the two primary EET actions in the heart. EET cell signaling mechanisms are tissue and organ specific and provide significant evidence for the existence of EET receptors. Additionally, pharmacological and genetic manipulations of EETs and sEH have demonstrated a contribution for this metabolic pathway to cardiovascular diseases. Given the impact of EETs to cardiovascular physiology, there is emerging evidence that development of EET-based therapeutics will be beneficial for cardiovascular diseases. PMID- 22298654 TI - Regulation and function of the FGF23/klotho endocrine pathways. AB - Calcium (Ca(2+)) and phosphate (PO(4)(3-)) homeostasis are coordinated by systemic and local factors that regulate intestinal absorption, influx and efflux from bone, and kidney excretion and reabsorption of these ions through a complex hormonal network. Traditionally, the parathyroid hormone (PTH)/vitamin D axis provided the conceptual framework to understand mineral metabolism. PTH secreted by the parathyroid gland in response to hypocalcemia functions to maintain serum Ca(2+) levels by increasing Ca(2+) reabsorption and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] production by the kidney, enhancing Ca(2+) and PO(4)(3-) intestinal absorption and increasing Ca(2+) and PO(4)(3-) efflux from bone, while maintaining neutral phosphate balance through phosphaturic effects. FGF23 is a recently discovered hormone, predominately produced by osteoblasts/osteocytes, whose major functions are to inhibit renal tubular phosphate reabsorption and suppress circulating 1,25(OH)(2)D levels by decreasing Cyp27b1-mediated formation and stimulating Cyp24-mediated catabolism of 1,25(OH)(2)D. FGF23 participates in a new bone/kidney axis that protects the organism from excess vitamin D and coordinates renal PO(4)(3-) handling with bone mineralization/turnover. Abnormalities of FGF23 production underlie many inherited and acquired disorders of phosphate homeostasis. This review discusses the known and emerging functions of FGF23, its regulation in response to systemic and local signals, as well as the implications of FGF23 in different pathological and physiological contexts. PMID- 22298657 TI - Inhibition and termination of physiological responses by GTPase activating proteins. AB - Physiological processes are strictly organized in space and time. However, in cell physiology research, more attention is given to the question of space rather than to time. To function as a signal, environmental changes must be restricted in time; they need not only be initiated but also terminated. In this review, we concentrate on the role of one specific protein family involved in biological signal termination. GTPase activating proteins (GAPs) accelerate the endogenously low GTP hydrolysis rate of monomeric guanine nucleotide-binding proteins (GNBPs), limiting thereby their prevalence in the active, GTP-bound form. We discuss cases where defective or excessive GAP activity of specific proteins causes significant alteration in the function of the nervous, endocrine, and hemopoietic systems, or contributes to development of infections and tumors. Biochemical and genetic data as well as observations from human pathology support the notion that GAPs represent vital elements in the spatiotemporal fine tuning of physiological processes. PMID- 22298656 TI - Fast synaptic inhibition in spinal sensory processing and pain control. AB - The two amino acids GABA and glycine mediate fast inhibitory neurotransmission in different CNS areas and serve pivotal roles in the spinal sensory processing. Under healthy conditions, they limit the excitability of spinal terminals of primary sensory nerve fibers and of intrinsic dorsal horn neurons through pre- and postsynaptic mechanisms, and thereby facilitate the spatial and temporal discrimination of sensory stimuli. Removal of fast inhibition not only reduces the fidelity of normal sensory processing but also provokes symptoms very much reminiscent of pathological and chronic pain syndromes. This review summarizes our knowledge of the molecular bases of spinal inhibitory neurotransmission and its organization in dorsal horn sensory circuits. Particular emphasis is placed on the role and mechanisms of spinal inhibitory malfunction in inflammatory and neuropathic chronic pain syndromes. PMID- 22298659 TI - Hypoxic pulmonary vasoconstriction. AB - It has been known for more than 60 years, and suspected for over 100, that alveolar hypoxia causes pulmonary vasoconstriction by means of mechanisms local to the lung. For the last 20 years, it has been clear that the essential sensor, transduction, and effector mechanisms responsible for hypoxic pulmonary vasoconstriction (HPV) reside in the pulmonary arterial smooth muscle cell. The main focus of this review is the cellular and molecular work performed to clarify these intrinsic mechanisms and to determine how they are facilitated and inhibited by the extrinsic influences of other cells. Because the interaction of intrinsic and extrinsic mechanisms is likely to shape expression of HPV in vivo, we relate results obtained in cells to HPV in more intact preparations, such as intact and isolated lungs and isolated pulmonary vessels. Finally, we evaluate evidence regarding the contribution of HPV to the physiological and pathophysiological processes involved in the transition from fetal to neonatal life, pulmonary gas exchange, high-altitude pulmonary edema, and pulmonary hypertension. Although understanding of HPV has advanced significantly, major areas of ignorance and uncertainty await resolution. PMID- 22298660 TI - Capecitabine non-adherence: exploration of magnitude, nature and contributing factors. AB - OBJECTIVES: The prescribing of oral chemotherapy agents previously available only in the intravenous formulation, such as capecitabine, has afforded many benefits including reduced administration costs and improved patient acceptability. However, it has introduced the new challenge of ensuring patient adherence to therapy. It is therefore necessary to quantify adherence, and with a view to improving services, explore factors that may impact on medication taking behavior. METHODS: Patients with a diagnosis of breast or colorectal cancer and prescribed capecitabine were recruited from a UK teaching hospital. Data regarding self-reported adherence, beliefs about medicines, side effects, and satisfaction with information received about capecitabine were recorded. RESULTS: Non-adherence was reported by 23.3% of the 43 participants. Capecitabine therapy was perceived necessary by 97.6%, but almost one-third of participants had strong concerns. Side effects were reported by 80% of participants, with Palmar-Plantar erythrodysesthesia and fatigue most troubling participants. Complete satisfaction with information received was reported by 65% of participants; however, dissatisfaction about how to tell if capecitabine is working and the proposed duration of therapy was expressed by 42.9% and 37.3% of participants, respectively. CONCLUSIONS: Adherence to capecitabine is high with a strong conviction that the therapy is necessary. However, concerns were expressed regarding the experience of side effects. Patients have unmet information needs regarding the processes involved with monitoring capecitabine efficacy and determination of therapy duration. Healthcare professionals may therefore wish to consider a greater focus on involving patients in the monitoring of their care with respect to efficacy and planned treatment schedules. PMID- 22298661 TI - The cover. Snowscape with cows at Montfoucault. PMID- 22298662 TI - Patient-centered care model demands better physician-patient communication. PMID- 22298663 TI - Veterans health system cited by experts as a model for patient-centered care. PMID- 22298664 TI - FDA: Limited ban on cephalosporin use in major food-producing animals. PMID- 22298665 TI - Programs to reduce childhood obesity seem to work, say Cochrane reviewers. PMID- 22298666 TI - Panel advises tougher limits on lead exposure. PMID- 22298667 TI - Prostate cancer risk and vitamin E. PMID- 22298668 TI - Prostate cancer risk and vitamin E. PMID- 22298669 TI - ECMO centers and mortality from influenza A(H1N1). PMID- 22298670 TI - Benefits of male circumcision. PMID- 22298671 TI - Benefits of male circumcision. PMID- 22298658 TI - Endocytosis and signaling: cell logistics shape the eukaryotic cell plan. AB - Our understanding of endocytosis has evolved remarkably in little more than a decade. This is the result not only of advances in our knowledge of its molecular and biological workings, but also of a true paradigm shift in our understanding of what really constitutes endocytosis and of its role in homeostasis. Although endocytosis was initially discovered and studied as a relatively simple process to transport molecules across the plasma membrane, it was subsequently found to be inextricably linked with almost all aspects of cellular signaling. This led to the notion that endocytosis is actually the master organizer of cellular signaling, providing the cell with understandable messages that have been resolved in space and time. In essence, endocytosis provides the communications and supply routes (the logistics) of the cell. Although this may seem revolutionary, it is still likely to be only a small part of the entire story. A wealth of new evidence is uncovering the surprisingly pervasive nature of endocytosis in essentially all aspects of cellular regulation. In addition, many newly discovered functions of endocytic proteins are not immediately interpretable within the classical view of endocytosis. A possible framework, to rationalize all this new knowledge, requires us to "upgrade" our vision of endocytosis. By combining the analysis of biochemical, biological, and evolutionary evidence, we propose herein that endocytosis constitutes one of the major enabling conditions that in the history of life permitted the development of a higher level of organization, leading to the actuation of the eukaryotic cell plan. PMID- 22298672 TI - Benefits of male circumcision. PMID- 22298673 TI - Benefits of male circumcision. PMID- 22298674 TI - Physician medical identity theft. PMID- 22298675 TI - The ethical hazards and programmatic challenges of genomic newborn screening. PMID- 22298676 TI - Specialization in medicine: how much is appropriate? PMID- 22298677 TI - A piece of my mind. A doctor's kid. PMID- 22298678 TI - Variability in reexcision following breast conservation surgery. AB - CONTEXT: Health care reform calls for increasing physician accountability and transparency of outcomes. Partial mastectomy is the most commonly performed procedure for invasive breast cancer and often requires reexcision. Variability in reexcision might be reflective of the quality of care. OBJECTIVE: To assess hospital and surgeon-specific variation in reexcision rates following partial mastectomy. DESIGN, SETTING, AND PATIENTS: An observational study of breast surgery performed between 2003 and 2008 intended to evaluate variability in breast cancer surgical care outcomes and evaluate potential quality measures of breast cancer surgery. Women with invasive breast cancer undergoing partial mastectomy from 4 institutions were studied (1 university hospital [University of Vermont] and 3 large health plans [Kaiser Permanente Colorado, Group Health, and Marshfield Clinic]). Data were obtained from electronic medical records and chart abstraction of surgical, pathology, radiology, and outpatient records, including detailed surgical margin status. Logistic regression including surgeon-level random effects was used to identify predictors of reexcision. MAIN OUTCOME MEASURE: Incidence of reexcision. RESULTS: A total of 2206 women with 2220 invasive breast cancers underwent partial mastectomy and 509 patients (22.9%; 95% CI, 21.2%-24.7%) underwent reexcision (454 patients [89.2%; 95% CI, 86.5%-91.9%] had 1 reexcision, 48 [9.4%; 95% CI, 6.9%-12.0%] had 2 reexcisions, and 7 [1.4%; 95% CI, 0.4%-2.4%] had 3 reexcisions). Among all patients undergoing initial partial mastectomy, total mastectomy was performed in 190 patients (8.5%; 95% CI, 7.2%-9.5%). Reexcision rates for margin status following initial surgery were 85.9% (95% CI, 82.0%-89.8%) for initial positive margins, 47.9% (95% CI, 42.0% 53.9%) for less than 1.0 mm margins, 20.2% (95% CI, 15.3%-25.0%) for 1.0 to 1.9 mm margins, and 6.3% (95% CI, 3.2%-9.3%) for 2.0 to 2.9 mm margins. For patients with negative margins, reexcision rates varied widely among surgeons (range, 0% 70%; P = .003) and institutions (range, 1.7%-20.9%; P < .001). Reexcision rates were not associated with surgeon procedure volume after adjusting for case mix (P = .92). CONCLUSION: Substantial surgeon and institutional variation were observed in reexcision following partial mastectomy in women with invasive breast cancer. PMID- 22298680 TI - The challenge of developing quality measures for breast cancer surgery. PMID- 22298679 TI - Association of emergency department length of stay with safety-net status. AB - CONTEXT: Performance measures, particularly pay for performance, may have unintended consequences for safety-net institutions caring for disproportionate shares of Medicaid or uninsured patients. OBJECTIVE: To describe emergency department (ED) compliance with proposed length-of-stay measures for admissions (8 hours or 480 minutes) and discharges, transfers, and observations (4 hours or 240 minutes) by safety-net status. DESIGN, SETTING, AND PARTICIPANTS: The 2008 National Hospital Ambulatory Medical Care Survey (NHAMCS) ED data were stratified by safety-net status (Centers for Disease Control and Prevention definition) and disposition (admission, discharge, observation, transfer). The 2008 NHAMCS is a national probability sample of 396 hospitals (90.2% unweighted response rate) and 34 134 patient records. Visits were excluded for patients younger than 18 years, missing length-of-stay data or dispositions of missing, other, left against medical advice, or dead on arrival. Median and 90th percentile ED lengths of stay were calculated for each disposition and admission/discharge subcategories (critical care, psychiatric, routine) stratified by safety-net status. Multivariable analyses determined associations with length-of-stay measure compliance. MAIN OUTCOME MEASURES: Emergency Department length-of-stay measure compliance by disposition and safety-net status. RESULTS: Of the 72.1% ED visits (N = 24 719) included in the analysis, 42.3% were to safety-net EDs and 57.7% were to non-safety-net EDs. The median length of stay for safety-net was 269 minutes (interquartile range [IQR], 178-397 minutes) for admission vs 281 minutes (IQR, 178-401 minutes) for non-safety-net EDs; 156 minutes (IQR, 95-239 minutes) for discharge vs 148 minutes (IQR, 88-238 minutes); 355 minutes (IQR, 221-675 minutes) for observations vs 298 minutes (IQR, 195-440 minutes); and 235 minutes (IQR, 155-378 minutes) for transfers vs 239 minutes (IQR, 142-368 minutes). Safety-net status was not independently associated with compliance with ED length of-stay measures; the odds ratio was 0.83 for admissions (95% CI, 0.52-1.34); 1.03 for discharges (95% CI, 0.83-1.27); 1.05 for observations (95% CI, 0.57 1.95), 1.30 for transfers (95% CI, 0.70-2.45]); or subcategories except for psychiatric discharges (1.67, [95% CI, 1.02-2.74]). CONCLUSION: Compliance with proposed ED length-of-stay measures for admissions, discharges, transfers, and observations did not differ significantly between safety-net and non-safety-net hospitals. PMID- 22298681 TI - National reporting of emergency department length of stay: challenges, opportunities, and risks. PMID- 22298682 TI - JAMA patient page. Prostatitis. PMID- 22298683 TI - Phytosterols play a key role in plant innate immunity against bacterial pathogens by regulating nutrient efflux into the apoplast. AB - Bacterial pathogens colonize a host plant by growing between the cells by utilizing the nutrients present in apoplastic space. While successful pathogens manipulate the plant cell membrane to retrieve more nutrients from the cell, the counteracting plant defense mechanism against nonhost pathogens to restrict the nutrient efflux into the apoplast is not clear. To identify the genes involved in nonhost resistance against bacterial pathogens, we developed a virus-induced gene silencing-based fast-forward genetics screen in Nicotiana benthamiana. Silencing of N. benthamiana SQUALENE SYNTHASE, a key gene in phytosterol biosynthesis, not only compromised nonhost resistance to few pathovars of Pseudomonas syringae and Xanthomonas campestris, but also enhanced the growth of the host pathogen P. syringae pv tabaci by increasing nutrient efflux into the apoplast. An Arabidopsis (Arabidopsis thaliana) sterol methyltransferase mutant (sterol methyltransferase2) involved in sterol biosynthesis also compromised plant innate immunity against bacterial pathogens. The Arabidopsis cytochrome P450 CYP710A1, which encodes C22-sterol desaturase that converts beta-sitosterol to stigmasterol, was dramatically induced upon inoculation with nonhost pathogens. An Arabidopsis Atcyp710A1 null mutant compromised both nonhost and basal resistance while overexpressors of AtCYP710A1 enhanced resistance to host pathogens. Our data implicate the involvement of sterols in plant innate immunity against bacterial infections by regulating nutrient efflux into the apoplast. PMID- 22298684 TI - Systematic evaluation of the upper airway in the adult population of Sao Paulo, Brazil. AB - OBJECTIVES: To study the prevalence of otorhinolaryngologic symptoms and findings of physical examination of the upper airway (UA) of a representative sample of the adult population of Sao Paulo, Brazil, and the association between these findings. STUDY DESIGN: Cross-sectional survey. SETTING: Population sample. METHODS: A total of 1101 randomly selected volunteers representing the adult population of Sao Paulo according to sex, age, and socioeconomic class were included in this study. Otorhinolaryngological evaluation included investigation of nasal complaints, physical examination of the UA, and a facial inspection. RESULTS: A total of 993 volunteers (53.9% women), with a mean age of 41.8 +/- 0.89 years, underwent otorhinolaryngologic examination. The most prevalent symptoms were the following: symptoms suggestive of rhinitis (44.9%), snoring (42.8%), mouth breathing (39.3%), and nasal obstruction (33.3%). In physical examination, the most common findings were a web palate (redundant posterior pillar; 62.9%), septum deviation (56.9%), and inferior turbinate hypertrophy (37.7%). Significant associations were found between nasal obstruction and septum deviations, inferior turbinate hypertrophy, high-arched palate, and class II dental occlusion; between symptoms of rhinitis and inferior turbinate hypertrophy; and between snoring and obstructive deviated septum, modified Mallampatti grades III and IV, increased neck circumference, and age greater than or equal to 50 years. CONCLUSIONS: The prevalence of otorhinolaryngologic symptoms and alterations in physical examination of the UA were high in the adult population of Sao Paulo, Brazil. The snoring and nasal symptoms were significantly associated with findings from UA physical examination and inspection of the facial skeleton. PMID- 22298685 TI - MRSA contaminated venepuncture tourniquets in clinical practice. AB - INTRODUCTION: Meticillin-resistant Staphylococcus aureus (MRSA) hospital-acquired infection is associated with increased patient mortality. National guidelines state that shared patient equipment must be cleaned after use. The authors sought to identify MRSA contamination in a sample of non-disposable venepuncture tourniquets and audit cleaning habits between patient contacts. MATERIALS AND METHODS: Fifty tourniquets were collected from junior doctors, nursing staff and wards from two district general hospitals in Essex, UK in 2007. A questionnaire was completed at the time of collection for each tourniquet. The tourniquets were cultured using standard microbiology techniques. FINDINGS: 18/50 (36%) tourniquets were positive for S. aureus and of these 6/50 (12%) were MRSA positive. 33/43 (77%) healthcare professionals using non-disposable tourniquets for venepuncture made no attempts at cleaning their tourniquets. 10/43 (23%) staff admitted to cleaning their tourniquets. The tourniquets were used for an average of 14 weeks on approximately three different patients per day. 30/50 (60%) tourniquets were visibly soiled and of these 13 were blood stained and 20/50 (40%) appeared 'clean'. Worn tourniquets when compared with the 'clean' tourniquets were more likely to be contaminated with S. aureus, 15/30 (50%) vs 3/20 (15%), and MRSA 5/30 (17%) vs 1/20 (5%). CONCLUSION: Non-disposable venepuncture tourniquets are contaminated with MRSA and pose a risk to patients. The majority of clinical staff do not clean them between patient contacts as recommended by guidelines. The use of non-disposable venepuncture tourniquets should be abandoned. The introduction of disposable tourniquets to clinical practice should be an adjunct to current measures for MRSA prevention. PMID- 22298686 TI - The effects of D-fenfluramine on mood and performance, and on neuroendocrine indicators of 5-HT function. AB - D-fenfluramine has multiple actions which enhance 5-HT transmission and make it a useful neuroendocrine challenge agent, but little is known of its effects on mood or performance. In this study, two doses (15 and 30 mg) and placebo were administered to six male and six female healthy volunteers according to a double blind, cross-over design. Blood was sampled and self-ratings completed pre- and hourly up to 5 h post-challenge. Performance tests were administered pre- and at 2 and 4 h. Plasma concentrations of prolactin and cortisol decreased after all treatments at 1 h and then increased post-drug to a peak at 4 h. Body temperature showed a similar pattern. D-fenfluramine was well tolerated with few side effects. It caused only minor sedation and little psychomotor impairment but there was some decrement in episodic memory. The 30 mg dose produced a mild anxiolytic and anti-aggressive action. PMID- 22298687 TI - Behavioural interaction between the NMDA antagonist MK-801 and the dopaminergic antagonist haloperidol: support for a balance model. AB - One hundred and four male Sprague-Dawley rats were divided into three experiments. The first two experiments were to assess the effect of different MK 801 doses (0.1-0.3 mg/kg) and combinations of MK-801/ haloperidol (0.3/0.1-0.5 mg/kg) on locomotor behaviour. The animals from the third experiment were administered either saline, MK-801 (0.3 mg/kg), haloperidol (0.5 mg/kg) or MK 801/haloperidol (0.3/0.5 mg/kg). Locomotor activity measurements showed that the NMDA antagonist MK-801 induced a dose-dependent hyperactivity, while haloperidol, the D-2 dopamine receptor antagonist, induced hypoactivity. Significantly the highest doses of combined MK-801/haloperidol treatment (0.3/0.5 mg/kg) showed behavioural equivalence to the saline animals in both total locomotion, locomotion patterns and within-session habituation. Thus, the behavioural effects of each drug given alone were cancelled when the drugs were given together. This cancellation effect could not be ascribed to direct drug interference effects on dopamine metabolism since the ex vivo biochemical data revealed that the combined MK-801/haloperidol (0.3/0.5 mg/kg) treatment increased dopamine metabolism to the same extent as haloperidol given alone. None of the drug treatments, however, had any effect on brain serotonin metabolism. Serum measurement indicated that dopamine, homovanillic acid, 3,4-dihydroxyphenyl-acetic acid, 5-hydroxyindole-3 acetic acid, norepinephrine and corticosterone were not differentially affected by the drug treatment. Haloperidol-treated animals, however, had higher serum serotonin concentration than saline-treated animals. Taken together, these results support the hypothesis that the effect of MK-801 on behaviour is independent of biochemical changes in dopaminergic neuro transmission per se. Rather, the present results support the hypothesis of a glutamatergic dopaminergic balance which when disturbed leads to behavioural changes along an excitatory-inhibitory behavioural gradient. PMID- 22298688 TI - Nicotine-induced purposeless chewing in rats: possible dopamine receptor mediation. AB - Intraperitoneal (i.p.) administration of nicotine to rats induced purposeless chewing. The response induced by different doses of the drug (0.0001, 0.001, 0.01 and 0.1 mg/kg) seems to be dose dependent, with a maximum effect at 0.01 mg/kg and then decreasing at a higher dose (0.1 mg/kg). Pre-treatment of animals with the nicotine antagonist mecamylamine (0.01 and 0.1 mg/kg, 30 min) and the D-2 receptor antagonist sulpiride (12.5-100 mg/kg, 90 min), but not the D-1 antagonist SCH 23390 (0.01 and 0.05 mg/kg, 30 min), decreased the chewing induced by nicotine (0.01 mg/kg). When animals were pre-treated with propranolol (5 and 10 mg/kg) 60 min, reserpine (2.5 mg/kg) 18 h or alpha-methyl-p-tyrosine (alpha MPT; 250 mg/kg) 60 min before nicotine, the effect of the drug was reduced. However, reserpine (2.5 mg/kg) at 18 h plus alpha-MPT (250 mg/kg) 60 min prior to nicotine completely inhibited the drug response. Pre-treatment of animals with phenoxybenzamine (2.5 and 5 mg/kg i.p., 60 min) or atropine (5 and 10 mg/kg) did not change the nicotine response significantly. It is concluded that nicotine- induced purposeless chewing is mediated through dopaminergic and nicotinic mechanisms. PMID- 22298689 TI - Nicotine-induced hypothermia through an indirect dopaminergic mechanism. AB - The effect of nicotine on core body temperature was studied in mice. Intraperitoneal (i.p.) injection of nicotine (0.5, 1 and 2 mg/kg) induced a dose dependent hypothermia. The response was inhibited by reserpine (5 mg/kg), the centrally active nicotinic receptor antagonist mecamylamine (0.1-1 mg/kg) and the D-2 dopamine receptor antagonist sulpiride (25-100 mg/kg). The beta-adrenoceptor antagonist propranolol (5 and 10 mg/kg) and the serotonergic blocker methysergide (5 and 10 mg/kg) did not inhibit but increased the nicotine response. The alpha adrenoceptor antagonist phenoxybenzamine, the antimuscarinic agent atropine, the D-1 dopamine receptor antagonist SCH 23390, the peripheral dopamine antagonist domperidone and the peripheral nicotinic antagonist hexamethonium did not alter the nicotine-induced hypothermia. It is concluded that nicotine may cause a fall in core body temperature through a central dopaminergic mechanism. PMID- 22298690 TI - In vivo effects of carbamazepine and haloperidol on GABA neurotransmission and LH secretion. AB - The in vivo effects of carbamazepine (CBZ) and haloperidol (HAL) on the neuroendocrine pre-optico-pituitary feedback system were studied by local application of the drugs, in single and in combination mode, through a push-pull cannula into the pre-optic area and measurement of their local effects on gamma aminobutyric acid (GABA) and their distant effects on a subsequent biological response: the pituitary luteinizing hormone (LH) secretion. The perfusion flow rate was 20 MUl cerebrospinal fluid (CSF)/min; the fraction period was 15 min. Perfusion with 8 MUg CBZ/ml CSF caused a reduction in pre-optic pre-synaptic GABA release and, concomitantly, a suppression of plasma LH levels. Application of 100 ng HAL/ml CSF also caused a reduction in GABA release, but no significant change in plasma LH levels. During the combined perfusion, the effects of CBZ and HAL did not add up with regard to the pre-optic GABA release. These results suggest that both drugs interact with the GABA system, but they may involve two different mechanisms of action. Due to the known inhibitory role of pre-optic GABA in pituitary LH secretion, it can be inferred that, in contrast to HAL, CBZ increases post-synaptic GABAergic transmission. PMID- 22298691 TI - Amnesia following gastroscopy with midazolam: a comparison in two age groups. AB - Forty patients, in two age groups, undergoing gastroscopy, received intravenous midazolam as the sole pre- medication. Mean ages were 35 (range 19-47) and 65.5 (range 53-75) and mean dosages 4.52 and 5.82 mg, respectively in the two groups. Neuropsychological testing pre- and post-medication comprised the Rey auditory verbal learning test (RAVLT), word association test, digit span and face memory test. The elderly group gave significantly more false-positive responses on recognition recall on the RAVLT and had significant impairment of reverse digit span. Following midazolam, in both age groups there was a significantly reduced rate of verbal learning and a marked deficit in delayed free recall coupled with substantial preservation of recognition recall. Word fluency and forward digit span were not affected. There was an increase in false-positive responses for face memory. These findings are consistent with a specific processing deficit affecting the acquisition of episodic long-term memory. PMID- 22298692 TI - Effects of ritanserin and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in the murine elevated plus-maze test of anxiety: an ethopharmacological study. AB - The 5-HT(2A/2c) receptor antagonist, ritanserin, has produced highly variable results in animal models of anxiety. The present study addressed the effects of this compound (0.5-5.0 mg/kg) and those of the 5-HT(2A/2C) receptor agonist, 1 (2,5-dimethoxy-4-iodophenyl)-2-aminopropane (0.25-1.0 mg/kg), in an ethological version of the murine elevated plus-maze paradigm. In marked contrast to the potent effects produced by other compounds (anxiolytic and anxiogenic) under identical test conditions, results show that, over the dose ranges tested, neither compound significantly altered behavioural profiles. Findings are discussed in relation to the question of receptor affinities and the need for studies on compounds with more selective profiles of action. PMID- 22298693 TI - The treatment of Alzheimer's disease. PMID- 22298694 TI - Benzodiazepines and GABA hypothesis of schizophrenia. AB - Clinical and experimental studies pertinent for demonstrating the antipsychotic potential of benzodiazepines (BDZ) and the involvement of gamma-aminobutyric acid (GABA) in the origin of schizophrenia are reviewed. It is shown that, due to severe methodological problems and pitfalls, placebo-controlled, double-blind studies do not permit unequivocal conclusions on the efficacy of BDZs, but neither do they completely disprove it. Furthermore, at first glance, confusing and controversial findings in animal models indicate a bi-directionality of effects of full BDZ agonists on dopamine-mediated functions, which may perhaps be explained by (i) anatomical and functional organization of the GABA-dopamine system in the nigro-striatal and ventro tegmental area, and (ii) the regional non selectivity of action of these drugs. The recent demonstration of structural polymorphism of the GABA(A)-BDZ receptor complex and heterogeneous distribution of sets of subunits of the GABA( A)-BDZ receptor in the brain, suggests possibilities for development of partial BDZ agonists showing greater regional selectivity of action and thus potentially more specific antipsychotic action. Initial clinical results with bretazenil (Ro 16-6028), a partial BDZ agonist, in acute schizophrenia are, in this respect, an encouraging lead to be followed further. PMID- 22298695 TI - Clozapine can cause hallucinations by inducing complex partial seizures of temporal lobe origin (temporal lobe epilepsy). A potentially serious complication in the management of schizophrenia with clozapine. AB - A young man with schizophrenia had persistent auditory hallucinations which responded well to clozapine but subsequently developed a different pattern of brief, joint visual and auditory hallucinations which were confirmed as being due to complex partial seizures of temporal lobe origin. He had no history of epilepsy prior to taking clozapine and the subsequent hallucinations could be mistaken for a deterioration in the schizophrenia, leading to a further increase in clozapine dose. PMID- 22298697 TI - Kynurenine potentiates the DOI head shake in mice. PMID- 22298696 TI - Fluparoxan in male erectile disorder: a case report. AB - During a protocol study for the efficacy of fluparoxan (a noradrenergic alpha(2) antagonist) in depression, a positive effect on male erectile impotence has been observed in one case, with no important secondary effects. This result confirms the involvement of alpha(2)-antagonists in the handling of male impotence. The action on the erectile disorder appeared slightly before the antidepressive effect (2-3 weeks) and lasted for 6 weeks after the discontinuation of treatment, suggesting that the effects on impotence were not a mere reflection of the antidepressive action. PMID- 22298698 TI - Keep taking the tablets? Inadequate controls for concurrent psychotropic medication in studies of psychological treatments for panic disorder. PMID- 22298699 TI - Abstracts: the psychopharmacology of alcohol and alcoholism. PMID- 22298700 TI - Inferring coancestry in population samples in the presence of linkage disequilibrium. AB - In both pedigree linkage studies and in population-based association studies there has been much interest in the use of modern dense genetic marker data to infer segments of gene identity by descent (ibd) among individuals not known to be related, to increase power and resolution in localizing genes affecting complex traits. In this article, we present a hidden Markov model (HMM) for ibd among a set of chromosomes and describe methods and software for inference of ibd among the four chromosomes of pairs of individuals, using either phased (haplotypic) or unphased (genotypic) data. The model allows for missing data and typing error, but does not model linkage disequilibrium (LD), because fitting an accurate LD model requires large samples from well-studied populations. However, LD remains a major confounding factor, since LD is itself a reflection of coancestry at the population level. To study the impact of LD, we have developed a novel simulation approach to generate realistic dense marker data for the same set of markers but at varying levels of LD. Using this approach, we present results of a study of the impact of LD on the sensitivity and specificity of our HMM model in estimating segments of ibd among sets of four chromosomes and between genotype pairs. We show that, despite not incorporating LD, our model has been quite successful in detecting segments as small as 10(6) bp (1 Mpb); we present also comparisons with fastIBD which uses an LD model in estimating ibd. PMID- 22298701 TI - A test for selection employing quantitative trait locus and mutation accumulation data. AB - Evolutionary biologists attribute much of the phenotypic diversity observed in nature to the action of natural selection. However, for many phenotypic traits, especially quantitative phenotypic traits, it has been challenging to test for the historical action of selection. An important challenge for biologists studying quantitative traits, therefore, is to distinguish between traits that have evolved under the influence of strong selection and those that have evolved neutrally. Most existing tests for selection employ molecular data, but selection also leaves a mark on the genetic architecture underlying a trait. In particular, the distribution of quantitative trait locus (QTL) effect sizes and the distribution of mutational effects together provide information regarding the history of selection. Despite the increasing availability of QTL and mutation accumulation data, such data have not yet been effectively exploited for this purpose. We present a model of the evolution of QTL and employ it to formulate a test for historical selection. To provide a baseline for neutral evolution of the trait, we estimate the distribution of mutational effects from mutation accumulation experiments. We then apply a maximum-likelihood-based method of inference to estimate the range of selection strengths under which such a distribution of mutations could generate the observed QTL. Our test thus represents the first integration of population genetic theory and QTL data to measure the historical influence of selection. PMID- 22298702 TI - Roles for receptors, pheromones, G proteins, and mating type genes during sexual reproduction in Neurospora crassa. AB - Here we characterize the relationship between the PRE-2 pheromone receptor and its ligand, CCG-4, and the general requirements for receptors, pheromones, G proteins, and mating type genes during fusion of opposite mating-type cells and sexual sporulation in the multicellular fungus Neurospora crassa. PRE-2 is highly expressed in mat a cells and is localized in male and female reproductive structures. Deltapre-2 mat a females do not respond chemotropically to mat A males (conidia) or form mature fruiting bodies (perithecia) or meiotic progeny (ascospores). Strains with swapped identity due to heterologous expression of pre 2 or ccg-4 behave normally in crosses with opposite mating-type strains. Coexpression of pre-2 and ccg-4 in the mat A background leads to self-attraction and development of barren perithecia without ascospores. Further perithecial development is achieved by inactivation of Sad-1, a gene required for meiotic gene silencing. Findings from studies involving forced heterokaryons of opposite mating-type strains show that presence of one receptor and its compatible pheromone is necessary and sufficient for perithecial development and ascospore production. Taken together, the results demonstrate that although receptors and pheromones control sexual identity, the mating-type genes (mat A and mat a) must be in two different nuclei to allow meiosis and sexual sporulation to occur. PMID- 22298703 TI - Neural maintenance roles for the matrix receptor dystroglycan and the nuclear anchorage complex in Caenorhabditis elegans. AB - Recent studies in Caenorhabditis elegans have revealed specific neural maintenance mechanisms that protect soma and neurites against mispositioning due to displacement stresses, such as muscle contraction. We report that C. elegans dystroglycan (DG) DGN-1 functions to maintain the position of lumbar neurons during late embryonic and larval development. In the absence of DGN-1 the cell bodies of multiple lumbar neuron classes are frequently displaced anterior of their normal positions. Early but not later embryonic panneural expression of DGN 1 rescues positional maintenance, suggesting that dystroglycan is required for establishment of a critical maintenance pathway that persists throughout later developmental stages. Lumbar neural maintenance requires only a membrane-tethered N-terminal domain of DGN-1 and may involve a novel extracellular partner for dystroglycan. A genetic screen for similar lumbar maintenance mutants revealed a role for the nesprin/SYNE family protein ANC-1 as well as for the extracellular protein DIG-1, previously implicated in lumbar neuron maintenance. The involvement of ANC-1 reveals a previously unknown role for nucleus-cytoskeleton interactions in neural maintenance. Genetic analysis indicates that lumbar neuron position is maintained in late embryos by parallel DGN-1/DIG-1 and ANC-1 dependent pathways, and in larvae by separate DGN-1 and ANC-1 pathways. The effect of muscle paralysis on late embryonic- or larval-stage maintenance defects in mutants indicates that lumbar neurons are subject to both muscle contraction dependent and contraction-independent displacement stresses, and that different maintenance pathways may protect against specific types of displacement stress. PMID- 22298704 TI - Tissue architecture in the Caenorhabditis elegans gonad depends on interactions among fibulin-1, type IV collagen and the ADAMTS extracellular protease. AB - Molecules in the extracellular matrix (ECM) regulate cellular behavior in both development and pathology. Fibulin-1 is a conserved ECM protein. The Caenorhabditis elegans ortholog, FBL-1, regulates gonad-arm elongation and expansion by acting antagonistically to GON-1, an ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family protease. The elongation of gonad arms is directed by gonadal distal tip cells (DTCs). Here we report that a dominant mutation in the EMB-9/type IV collagen alpha1 subunit can compensate for loss of FBL-1 activity in gonadogenesis. A specific amino acid substitution in the noncollagenous 1 (NC1) domain of EMB-9 suppressed the fbl-1 null mutant. FBL 1 was required to maintain wild-type EMB-9 in the basement membrane (BM), whereas mutant EMB-9 was retained in the absence of FBL-1. EMB-9 (either wild type or mutant) localization in the BM enhanced PAT-3/beta-integrin expression in DTCs. In addition, overexpression of PAT-3 partially rescued the DTC migration defects in fbl-1 mutants, suggesting that EMB-9 acts in part through PAT-3 to control DTC migration. In contrast to the suppression of fbl-1(tk45), mutant EMB-9 enhanced the gonadal defects of gon-1(e1254), suggesting that it gained a function similar to that of wild-type FBL-1, which promotes DTC migration by inhibiting GON-1. We propose that FBL-1 and GON-1 control EMB-9 accumulation in the BM and promote PAT 3 expression to control DTC migration. PMID- 22298705 TI - Genetic analysis of complex interactions among components of the mitochondrial import motor and translocon in Saccharomyces cerevisiae. AB - A highly conserved, Hsp70-based, import motor, which is associated with the translocase on the matrix side of the inner mitochondrial membrane, is critical for protein translocation into the matrix. Hsp70 is tethered to the translocon via interaction with Tim44. Pam18, the J-protein co-chaperone, and Pam16, a structurally related protein with which Pam18 forms a heterodimer, are also critical components of the motor. Their N termini are important for the heterodimer's translocon association, with Pam18's and Pam16's N termini interacting in the intermembrane space and the matrix, respectively. Here, using the model organism Saccharomyces cerevisiae, we report the identification of an N terminal segment of Tim44, important for association of Pam16 with the translocon. We also report that higher amounts of Pam17, a nonessential motor component, are found associated with the translocon in both PAM16 and TIM44 mutants that affect their interaction with one another. These TIM44 and PAM16 mutations are also synthetically lethal with a deletion of PAM17. In contrast, a deletion of PAM17 has little, or no genetic interaction with a PAM18 mutation that affects translocon association of the Pam16:Pam18 heterodimer, suggesting a second role for the Pam16:Tim44 interaction. A similar pattern of genetic interactions and enhanced Pam17 translocon association was observed in the absence of the C terminus of Tim17, a core component of the translocon. We suggest the Pam16:Tim44 interaction may play two roles: (1) tethering the Pam16:Pam18 heterodimer to the translocon and (2) positioning the import motor for efficient engagement with the translocating polypeptide along with Tim17 and Pam17. PMID- 22298706 TI - TORC2 signaling is antagonized by protein phosphatase 2A and the Far complex in Saccharomyces cerevisiae. AB - The target of rapamycin (TOR) kinase, a central regulator of eukaryotic cell growth, exists in two essential, yet distinct, TOR kinase complexes in the budding yeast Saccharomyces cerevisiae: rapamycin-sensitive TORC1 and rapamycin insensitive TORC2. Lst8, a component of both TOR complexes, is essential for cell viability. However, it is unclear whether the essential function of Lst8 is linked to TORC1, TORC2, or both. To that end, we carried out a genetic screen to isolate lst8 deletion suppressor mutants. Here we report that mutations in SAC7 and FAR11 suppress lethality of lst8Delta and TORC2-deficient (tor2-21) mutations but not TORC1 inactivation, suggesting that the essential function of Lst8 is linked only to TORC2. More importantly, characterization of lst8Delta bypass mutants reveals a role for protein phosphatase 2A (PP2A) in the regulation of TORC2 signaling. We show that Far11, a member of the Far3-7-8-9-10-11 complex involved in pheromone-induced cell cycle arrest, interacts with Tpd3 and Pph21, conserved components of PP2A, and deletions of components of the Far3-7-8-9-10-11 complex and PP2A rescue growth defects in lst8Delta and tor2-21 mutants. In addition, loss of the regulatory B' subunit of PP2A Rts1 or Far11 restores phosphorylation to the TORC2 substrate Slm1 in a tor2-21 mutant. Mammalian Far11 orthologs FAM40A/B exist in a complex with PP2A known as STRIPAK, suggesting a conserved functional association of PP2A and Far11. Antagonism of TORC2 signaling by PP2A-Far11 represents a novel regulatory mechanism for controlling spatial cell growth of yeast. PMID- 22298707 TI - A general population genetic framework for antagonistic selection that accounts for demography and recurrent mutation. AB - Antagonistic selection--where alleles at a locus have opposing effects on male and female fitness ("sexual antagonism") or between components of fitness ("antagonistic pleiotropy")--might play an important role in maintaining population genetic variation and in driving phylogenetic and genomic patterns of sexual dimorphism and life-history evolution. While prior theory has thoroughly characterized the conditions necessary for antagonistic balancing selection to operate, we currently know little about the evolutionary interactions between antagonistic selection, recurrent mutation, and genetic drift, which should collectively shape empirical patterns of genetic variation. To fill this void, we developed and analyzed a series of population genetic models that simultaneously incorporate these processes. Our models identify two general properties of antagonistically selected loci. First, antagonistic selection inflates heterozygosity and fitness variance across a broad parameter range--a result that applies to alleles maintained by balancing selection and by recurrent mutation. Second, effective population size and genetic drift profoundly affect the statistical frequency distributions of antagonistically selected alleles. The "efficacy" of antagonistic selection (i.e., its tendency to dominate over genetic drift) is extremely weak relative to classical models, such as directional selection and overdominance. Alleles meeting traditional criteria for strong selection (N(e)s >> 1, where N(e) is the effective population size, and s is a selection coefficient for a given sex or fitness component) may nevertheless evolve as if neutral. The effects of mutation and demography may generate population differences in overall levels of antagonistic fitness variation, as well as molecular population genetic signatures of balancing selection. PMID- 22298708 TI - Flowering time in maize: linkage and epistasis at a major effect locus. AB - In a previous study, we identified a candidate fragment length polymorphism associated with flowering time variation after seven generations of selection for flowering time, starting from the maize inbred line F252. Here, we characterized the candidate region and identified underlying polymorphisms. Then, we combined QTL mapping, association mapping, and developmental characterization to dissect the genetic mechanisms responsible for the phenotypic variation. The candidate region contained the Eukaryotic Initiation Factor (eIF-4A) and revealed a high level of sequence and structural variation beyond the 3'-UTR of eIF-4A, including several insertions of truncated transposable elements. Using a biallelic single nucleotide polymorphism (SNP) (C/T) in the candidate region, we confirmed its association with flowering time variation in a panel of 317 maize inbred lines. However, while the T allele was correlated with late flowering time within the F252 genetic background, it was correlated with early flowering time in the association panel with pervasive interactions between allelic variation and the genetic background, pointing to underlying epistasis. We also detected pleiotropic effects of the candidate polymorphism on various traits including flowering time, plant height, and leaf number. Finally, we were able to break down the correlation between flowering time and leaf number in the progeny of a heterozygote (C/T) within the F252 background consistent with causal loci in linkage disequilibrium. We therefore propose that both a cluster of tightly linked genes and epistasis contribute to the phenotypic variation for flowering time. PMID- 22298709 TI - Understanding and predicting the fitness decline of shrunk populations: inbreeding, purging, mutation, and standard selection. AB - The joint consequences of inbreeding, natural selection, and deleterious mutation on mean fitness after population shrinkage are of great importance in evolution and can be critical to the conservation of endangered populations. I present simple analytical equations that predict these consequences, improving and extending a previous heuristic treatment. Purge is defined as the "extra" selection induced by inbreeding, due to the "extra" fitness disadvantage (2d) of homozygotes for (partially) recessive deleterious alleles. Its effect is accounted for by using, instead of the classical inbreeding coefficient f, a purged inbreeding coefficient g that is weighed by the reduction of the frequency of deleterious alleles caused by purging. When the effective size of a large population is reduced to a smaller stable value N (with Nd >= 1), the purged inbreeding coefficient after t generations can be predicted as g(t) ~ [(1 - 1/2N) g(t)(-1) + 1/2N](1 - 2d f(t)(-1)), showing how purging acts upon previously accumulated inbreeding and how its efficiency increases with N. This implies an early fitness decay, followed by some recovery. During this process, the inbreeding depression rate shifts from its ancestral value (delta) to that of the mutation-selection-drift balance corresponding to N (delta*), and standard selection cancels out the inbreeding depression ascribed to delta*. Therefore, purge and inbreeding operate only upon the remaining delta - delta*. The method is applied to the conservation strategy in which family contributions to the breeding pool are equal and is extended to make use of genealogical information. All these predictions are checked using computer simulation. PMID- 22298710 TI - Sensory organ remodeling in Caenorhabditis elegans requires the zinc-finger protein ZTF-16. AB - Neurons and glia display remarkable morphological plasticity, and remodeling of glia may facilitate neuronal shape changes. The molecular basis and control of glial shape changes is not well understood. In response to environmental stress, the nematode Caenorhabditis elegans enters an alternative developmental state, called dauer, in which glia and neurons of the amphid sensory organ remodel. Here, we describe a genetic screen aimed at identifying genes required for amphid glia remodeling. We previously demonstrated that remodeling requires the Otx-type transcription factor TTX-1 and its direct target, the receptor tyrosine kinase gene ver-1. We now find that the hunchback/Ikaros-like C2H2 zinc-finger factor ztf-16 is also required. We show that ztf-16 mutants exhibit pronounced remodeling defects, which are explained, at least in part, by defects in the expression of ver-1. Expression and cell-specific rescue studies suggest that ztf 16, like ttx-1, functions within glia; however, promoter deletion studies show that ztf-16 acts through a site on the ver-1 promoter that is independent of ttx 1. Our studies identify an important component of glia remodeling and suggest that transcriptional changes may underlie glial morphological plasticity in the sensory organs of C. elegans. PMID- 22298711 TI - Rapid and robust resampling-based multiple-testing correction with application in a genome-wide expression quantitative trait loci study. AB - Genome-wide expression quantitative trait loci (eQTL) studies have emerged as a powerful tool to understand the genetic basis of gene expression and complex traits. In a typical eQTL study, the huge number of genetic markers and expression traits and their complicated correlations present a challenging multiple-testing correction problem. The resampling-based test using permutation or bootstrap procedures is a standard approach to address the multiple-testing problem in eQTL studies. A brute force application of the resampling-based test to large-scale eQTL data sets is often computationally infeasible. Several computationally efficient methods have been proposed to calculate approximate resampling-based P-values. However, these methods rely on certain assumptions about the correlation structure of the genetic markers, which may not be valid for certain studies. We propose a novel algorithm, rapid and exact multiple testing correction by resampling (REM), to address this challenge. REM calculates the exact resampling-based P-values in a computationally efficient manner. The computational advantage of REM lies in its strategy of pruning the search space by skipping genetic markers whose upper bounds on test statistics are small. REM does not rely on any assumption about the correlation structure of the genetic markers. It can be applied to a variety of resampling-based multiple-testing correction methods including permutation and bootstrap methods. We evaluate REM on three eQTL data sets (yeast, inbred mouse, and human rare variants) and show that it achieves accurate resampling-based P-value estimation with much less computational cost than existing methods. The software is available at http://csbio.unc.edu/eQTL. PMID- 22298713 TI - Is the drug shortage affecting patient care in your critical care unit? PMID- 22298714 TI - Multisociety task force for critical care research: key issues and recommendations. PMID- 22298715 TI - Intra-abdominal hypertension and abdominal compartment syndrome: a comprehensive overview. AB - Intra-abdominal hypertension has a prevalence of at least 50% in the critically ill population and has been identified as an independent risk factor for death. Yet, many of the members of the critical care team do not assess for intra abdominal hypertension and are unaware of the consequences of untreated intra abdominal hypertension. These consequences can be abdominal compartment syndrome, multisystem organ failure, and death. This article provides an overview of the pathophysiology of intra-abdominal hypertension and abdominal compartment syndrome. In addition, the evidence-based definitions, guidelines, and recommendations of the World Society of the Abdominal Compartment Syndrome are presented. PMID- 22298716 TI - Shivering management during therapeutic temperature modulation: nurses' perspective. AB - Therapeutic temperature modulation, which incorporates mild hypothermia and maintenance of normothermia, is being used to manage patients resuscitated after cardiac arrest. Methods of modulating temperature include intravenous infusion of cold fluids and surface or endovascular cooling. During this therapy, the shiver response is activated as a defense mechanism in response to an altered set-point temperature and causes metabolic and hemodynamic stress for patients. Recognition of shivering according to objective and subjective assessments is vital for early detection of the condition. Once shivering is detected, treatment is imperative to avoid deleterious effects. The Bedside Shivering Assessment Scale can be used to determine the efficacy of interventions intended to blunt thermoregulatory defenses and can provide continual evaluation of patients' responses to the interventions. Nurses' knowledge and understanding of the harmful effects of shivering are important to effect care and prevent injury associated with uncontrolled shivering. PMID- 22298717 TI - Daily interruptions of sedation: a clinical approach to improve outcomes in critically ill patients. AB - The continuous infusion of sedative agents is often necessary for critically ill patients. However, it has been associated with several disadvantages. Numerous interventions to reduce these risks have been evaluated, including the practice of interrupting sedative infusions on a daily basis. A literature search was conducted, and 7 studies were reviewed to evaluate the safety and effectiveness of daily interruption of sedative infusions and its outcomes. The implementation of daily sedation interruptions was suggested to minimize multiple complications associated with continuous sedative infusions and was not associated with intensive care-related complications or long-term psychological effects. Additional studies have revealed perceived barriers to the implementation of daily sedation interruptions. Further randomized controlled trials enrolling larger, more diverse samples are needed to provide more evidence regarding the safety and effectiveness of this intervention. PMID- 22298718 TI - Strategies for improving patient safety: linking task type to error type. AB - This article reviews the connection between task type (skill based, rule based and knowledge based) and human error. Using real-life examples, each task type and error type is described in detail. Understanding how task type contributes to medical error enhances the ability of nurses to make meaningful changes in health care systems. Through error wisdom, nurses and other health care providers can more successfully navigate health care delivery and ultimately provide safer care to patients. PMID- 22298719 TI - Hospitalized infants who hurt: a sweet solution with oral sucrose. AB - Pain is harmful to newborn infants. Oral sucrose is safe, inexpensive, and effective at preventing and reducing pain in hospitalized babies who undergo invasive procedures. The sugar can be used alone or in combination with analgesics and other nonpharmacological interventions to provide analgesia. Parents expect nurses to serve as pain advocates for the parents' newborns and to protect the babies from needless suffering. It is incumbent upon nurses to stay abreast of the current evidence and integrate use of oral sucrose into daily pain management practice in emergency, acute, and critical care units. PMID- 22298720 TI - Hemodynamic instability: is it really a barrier to turning critically ill patients? PMID- 22298721 TI - Implementing a new practice when evidence-based literature is absent: guidelines regarding mobility of patients with left atrial catheters. PMID- 22298722 TI - Delirium assessment and management. PMID- 22298725 TI - Patients and their families weigh in on evidence-based hospital design. AB - BACKGROUND: In 2 landmark publications, the Institute of Medicine reported on significant deficiencies in our current health care system. In response, an area of research examining the role of the physical environment in influencing outcomes for patients and staff gained momentum. The concept of evidence-based design has evolved, and the development of structural guidelines for new hospital construction was instituted by the American Institute of Architects in 2006. OBJECTIVE: To determine perceptions of patients and their families of evidence based design features in a new heart center. METHODS: Hospitalized patients and their families, most of whom were in intensive care and step-down units, were surveyed and data from the Hospital Consumer Assessment of Healthcare Providers and Systems were reviewed to determine perceptions of evidence-based design features incorporated into a new heart center and to assess patients' satisfaction with the environment. Results Responses were reviewed and categorized descriptively. Five general environment topics of focus emerged: privacy, space, noise, light, and overall atmosphere. Characteristics perceived as being dissatisfying and satisfying are discussed. CONCLUSIONS: Critical care nurses must be aware of the current need to recognize how much the physical environment influences care delivery and take steps to maximize patients' safety, satisfaction, and quality of care. PMID- 22298726 TI - National survey of central venous catheter flushing in the intensive care unit. AB - BACKGROUND: Evidence is needed on the best solution for flushing central venous catheters. OBJECTIVE: To understand current flushing practices for short-term central venous catheters among critical care nurses before implementation of a randomized, controlled trial comparing physiological saline with heparin solution for flushing to maintain catheter patency. METHODS: A 6-item survey including demographic data was mailed to 2000 practicing critical care nurses in the United States. An additional 316 surveys were completed at the annual conference of the American Association of Critical-Care Nurses. RESULTS: Most (71.5%) of the 632 respondents who completed the survey were staff nurses. Most respondents (64.6%; 95% CI, 60.86%-68.34%) reported using physiological saline exclusively to flush central venous catheters and maintain patency. For heparin-containing solutions, the concentration and volume used varied. The most commonly reported volumes for flushing were 10 mL for saline (63%; 95% CI, 59.18%-66.82%) and 3 mL for heparin (50.2%; 95% CI, 43.5%-56.9%). CONCLUSION: Flushing practices for central venous catheters vary widely. A randomized controlled trial is needed to determine the optimal flushing solution to maintain short-term patency. PMID- 22298727 TI - Making the move: from bedside to camera-side. AB - The tele-intensive care unit (tele-ICU) uses sophisticated telemedicine technology and a remote team of critical care experts, including nurses, to provide continuous monitoring, assessment, and interventional services to a large number of patients across multiple ICUs. This new practice environment offers experienced critical care nurses an opportunity for career and knowledge expansion while reducing some of the physical and emotional risks encountered at the bedside. The role of the tele-ICU is still evolving but focuses on 4 areas of responsibility: performing virtual rounds, managing patient alerts, providing ICU support, and coaching or providing teaching moments. The transition from the bedside into the tele-ICU role can be complex as tele-ICU nurses encounter ICU acceptance barriers and a lack of or a change in professional identity. A formal orientation program focused on competency is necessary for the successful transition from bedside nurse to tele-ICU nurse. PMID- 22298728 TI - Abstract rule learning: the differential effects of lesions in frontal cortex. AB - Learning progressively more abstract stimulus-response mappings requires progressively more anterior regions of the lateral frontal cortex. Using an individual differences approach, we studied subjects with frontal lesions performing a hierarchical reinforcement-learning task to investigate how frontal cortex contributes to abstract rule learning. We predicted that subjects with lesions of the left pre-premotor (pre-PMd) cortex, a region implicated in abstract rule learning, would demonstrate impaired acquisition of second-order, as opposed to first-order, rules. We found that 4 subjects with such lesions did indeed demonstrate a second-order rule-learning impairment, but that these subjects nonetheless performed better than subjects with other frontal lesions in a second-order rule condition. This finding resulted from both their restricted exploration of the feature space and the task structure of this condition, for which they identified partially representative first-order rules. Significantly, across all subjects, suboptimal but above-chance performance in this condition correlated with increasing disconnection of left pre-PMd from the putative functional hierarchy, defined by reduced functional connectivity between left pre PMd and adjacent nodes. These findings support the theory that activity within lateral frontal cortex shapes the search for relevant stimulus-response mappings, while emphasizing that the behavioral correlate of impairments depends critically on task structure. PMID- 22298729 TI - Curvature processing dynamics in macaque area V4. AB - We have previously analyzed shape processing dynamics in macaque monkey posterior inferotemporal cortex (PIT). We described how early PIT responses to individual contour fragments evolve into tuning for multifragment shape configurations. Here, we analyzed curvature processing dynamics in area V4, which provides feedforward inputs to PIT. We contrasted 2 hypotheses: 1) that V4 curvature tuning evolves from tuning for simpler elements, analogous to PIT shape synthesis and 2) that V4 curvature tuning emerges immediately, based on purely feedforward mechanisms. Our results clearly supported the first hypothesis. Early V4 responses carried information about individual contour orientations. Tuning for multiorientation (curved) contours developed gradually over ~50 ms. Together, the current and previous results suggest a partial sequence for shape synthesis in ventral pathway cortex. We propose that early orientation signals are synthesized into curved contour fragment representations in V4 and that these signals are transmitted to PIT, where they are then synthesized into multifragment shape representations. The observed dynamics might additionally or alternatively reflect influences from earlier (V1, V2) and later (central and anterior IT) processing stages in the ventral pathway. In either case, the dynamics of contour information in V4 and PIT appear to reflect a sequential hierarchical process of shape synthesis. PMID- 22298730 TI - The extrinsic and intrinsic functional architectures of the human brain are not equivalent. AB - The brain's intrinsic functional architecture, revealed in correlated spontaneous activity, appears to constitute a faithful representation of its repertoire of evoked, extrinsic functional interactions. Here, using broad task contrasts to probe evoked patterns of coactivation, we demonstrate tight coupling between the brain's intrinsic and extrinsic functional architectures for default and task positive regions, but not for subcortical and limbic regions or for primary sensory and motor cortices. While strong correspondence likely reflects persistent or recurrent patterns of evoked coactivation, weak correspondence may exist for regions whose patterns of evoked functional interactions are more adaptive and context dependent. These findings were independent of task. For tight task contrasts (e.g., incongruent vs. congruent trials), evoked patterns of coactivation were unrelated to the intrinsic functional architecture, suggesting that high-level task demands are accommodated by context-specific modulations of functional interactions. We conclude that intrinsic approaches provide only a partial understanding of the brain's functional architecture. Appreciating the full repertoire of dynamic neural responses will continue to require task-based functional magnetic resonance imaging approaches. PMID- 22298731 TI - Analysis of time and space invariance of BOLD responses in the rat visual system. AB - Neuroimaging studies of functional magnetic resonance imaging (fMRI) and electrophysiology provide the linkage between neural activity and the blood oxygenation level-dependent (BOLD) response. Here, BOLD responses to light flashes were imaged at 11.7T and compared with neural recordings from superior colliculus (SC) and primary visual cortex (V1) in rat brain--regions with different basal blood flow and energy demand. Our goal was to assess neurovascular coupling in V1 and SC as reflected by temporal/spatial variances of impulse response functions (IRFs) and assess, if any, implications for general linear modeling (GLM) of BOLD responses. Light flashes induced high magnitude neural/BOLD responses reproducibly from both regions. However, neural/BOLD responses from SC and V1 were markedly different. SC signals followed the boxcar shape of the stimulation paradigm at all flash rates, whereas V1 signals were characterized by onset/offset transients that exhibited different flash rate dependencies. We find that IRF(SC) is generally time-invariant across wider flash rate range compared with IRF(V1), whereas IRF(SC) and IRF(V1) are both space invariant. These results illustrate the importance of measured neural signals for interpretation of fMRI by showing that GLM of BOLD responses may lead to misinterpretation of neural activity in some cases. PMID- 22298732 TI - Gender bias in the preclinical psychopharmacology of anxiety: male models for (predominantly) female disorders. PMID- 22298733 TI - A cognitive dysfunction in anxiety and its amelioration by effective treatment with SSRIs. AB - There is extensive research suggesting an abnormal selective attention to threat in anxiety disorders. We assessed the processing of emotional cognitions of physical anxiety, psycho-social fears, depression and positive affect in a cohort of 15 patients with active anxiety disorder (mostly panic) in comparison with a group of 15 depressed patients and 15 recovered panic patients after treatment with antidepressants (all selective serotonin re-uptake inhibitors) and an age- and sex-matched normal control group. Anxious patients showed delayed processing of emotional words (both negative and positive) compared with depressed patients. The successfully treated group showed no such interference and their responses were indistinguishable from controls. It would therefore appear that anxious patients (panic and generalized anxiety disorder) are affected primarily (but not exclusively) by themes of self-harm and psycho-social fears, and that this cognitive dysfunction in pathological anxiety is a state rather than trait feature of the condition, which is responsive to pharmacological intervention. PMID- 22298734 TI - Assessment of the interaction between a partial agonist and a full agonist of benzodiazepine receptors, based on psychomotor performance and memory, in healthy volunteers. AB - Potential interactions between the imidazopyridine anxiolytic alpidem and the full benzodiazepine agonist lorazepam were assessed in a randomized, double blind, four-way cross-over, placebo-controlled study in 16 healthy young male volunteers. Each volunteer received alpidem, 50 mg, or a placebo twice daily for 8 days with a 1- week wash-out interval. The interaction between alpidem, at the steady state, and a single oral dose of lorazepam 2 mg or a placebo was assessed after concomitant administration on days 7 or 9 of each treatment period. Psycho motor performance and cognitive function were evaluated before and 2, 4, 6 and 8 h post-dose, using objective tests [critical flicker fusion threshold (CFF), choice reaction time (CRT), digit-symbol substitution (DSST), body sway and short term memory (Sternberg memory scanning)] and self-ratings [line analogue rating scales: (LARS)]. Long-term memory (delayed free recall and recognition of pictures) was assessed before the dose and 2 and 4 h post-dose. Pharmacodynamic interactions were evaluated by applying repeated measures ANOVA to a 2 x 2 factorial interaction model. Alpidem, 50 mg twice daily at the steady state, was free of any clinically relevant detrimental effects on skilled performance, information processing or memory. In contrast, a single 2 mg dose of lorazepam induced marked impairment of psychomotor performance and cognitive function (significant reductions in CFF and DSST and increases in CRT and body sway), as well as subjective sedation from 2 to 8 h post-dose, depending on the test used. In addition, lorazepam induced anterograde amnesia, characterized by a decrease in delayed free recall and recognition, and a deficit in short-term memory. Finally, alpidem 50 mg did not potentiate the detrimental effects of lorazepam 2 mg. On the contrary, alpidem significantly antagonized the lorazepam-induced CRT increase and anterograde amnesia, and produced similar trends on most of the other cognitive parameters; thus, the results obtained with the combination of alpidem and lorazepam consistently indicated less impairment than those measured after lorazepam alone. These results are consistent with the suggested partial agonsist properties of alpidem at the benzodiazepine receptor and indicate that such properties can be assessed in humans based on antagonism of the effects of a full agonist. PMID- 22298735 TI - An assessment of resedation following flumazenil-induced antagonism of intravenous midazolam: comparison of psychomotor and amnesic recovery with a non sedated reference group. AB - The specific benzodiazepine antagonist flumazenil can enhance patient recovery following local anaesthetic day-case surgery performed under sedation. However, in view of its short elimination half-life, concerns have been expressed about the risk of resedation following its use. An open, randomised, parallel group study was designed to explore this question. Eighty-five patients were studied. Group A (n=43) patients underwent local anaesthetic cystoscopy with intravenous (i.v.) midazolam sedation. Following cystoscopy, and 30 min after the injection of midazolam, a bolus dose of flumazenil (0.5 mg i.v.) was given. Group B (n=42) patients underwent no operation and received no drugs but, in all other respects, were treated in an identical fashion to patients in group A. Tests of psychomotor function and memory were administered at baseline and again at 0.5, 1, 2, 3 and 4 h (or equivalent times for group B patients) following the injection of flumazenil. The test results showed no evidence of resedation, but there was evidence of incomplete reversal, as shown by significant differences in critical flicker fusion and delayed word recall at the 0.5-h test point. Group B patients showed no evidence of practice effects but did demonstrate an impairment in test performance possibly related to motivational factors. In conclusion, this study provides no evidence of resedation when using flumazenil to reverse the acute effects of midazolam. Incomplete reversal of amnesia need not delay patient discharge but has important implications with respect to the timing and nature of information imparted to patients prior to their release from hospital. PMID- 22298736 TI - Effects of diazepam on encoding processes. AB - Benzodiazepines are known to induce amnesic effects. To specify these effects more precisely, 40 healthy volunteers were given 15 mg diazepam or placebo. Effects on a chain of encoding operations were investigated: activation of memory representations, spreading of activation, semantic encoding and organizational processes. The diazepam group performed tasks consistently slower, although spreading of activation and semantic encoding were not affected by diazepam. Rather, diazepam subjects benefited less from opportunities to organize to-be learned material. It is suggested that cognitive processes are slowed down after diazepam intake. This may also have implications for the organization of to-be learned material. PMID- 22298737 TI - The effects of inhaled nitrous oxide on some measures of attention. AB - This study compared the sensitivity of various measures of attention to the effects of CNS depression, using a randomised single-blind two-period cross-over study. Nineteen healthy volunteers, 10 males and nine females, aged 20-49 took part in a single session in which they inhaled 15% nitrous oxide in oxygen or 100% oxygen (placebo) through a face-mask for 45 min, followed by a 10-min interval after which they received the other treatment in counterbalanced order. They performed a battery of five attention tasks and completed visual analogue scales starting 10 min after the beginning of each inhalation period. The most sensitive measures of the effects of this dose of nitrous oxide were letter cancellation, which had three target letters to cancel, and an auditory attention task with different stimuli to the two ears. Measures of concentrated attention without distractors (continuous attention task and continuous performance task) were less sensitive, though clear effects were seen at these doses. Tests of differing complexities may involve distinct functions which could be differentially affected by different classes of drug. Thus both simple and more complex tasks should be represented in studies assessing attentional function in detail. PMID- 22298738 TI - A comparison of augmenting central serotonin and noradrenaline function in healthy subjects: implications for studies on the neurochemistry of anxiety. AB - Biochemical and psychophysiological effects of augmenting serotonergic and noradrenergic function were compared in 12 normal volunteers. Fluvoxamine (100 mg), a serotonin (5-HT) re-uptake inhibitor, maprotiline (75 mg), a noradrenaline re-uptake inhibitor, and placebo were given for 7 days each to each subject. Subjects were tested pre-drug on days 1, 4 and 8 of each treatment. Catecholamines in 24 h urine, 'platelet-rich' plasma 5-HT and hormones, EEG, auditory evoked response, skin conductance, and bodily and psychological responses were monitored. Augmentation of central 5-HT by fluvoxamine was demonstrated by the decrease of 5-HT plasma levels. Fluvoxamine also reduced urinary dopamine, indicating a decrease in dopamine metabolism in response to augmentation of 5-HT function. Decrease in pulse rate, loss of appetite and a mild arousing effect were also detected with administration of fluvoxamine. Thus, further investigations on the neuro chemistry of anxiety disorders should include the study of mechanisms of interaction of neurotransmitters. PMID- 22298739 TI - The 5-HT3 antagonist ondansetron reduces gastrointestinal side effects induced by a specific serotonin re-uptake inhibitor in man. AB - The selective serotonin re-uptake inhibitors (SSRIs) are increasingly being used to treat depression and anxiety disorders. Gastrointestinal (GI) symptoms are the main side effects, probably resulting from the stimulation of central or peripheral 5-HT receptors. The present double-blind, placebo-controlled study was undertaken to see if the GI side effects of fluvoxamine could be attenuated by the co-administration of the 5-HT(3) antagonist ondansetron. The results demonstrate that, in volunteers, a single 100 mg oral dose of fluvoxamine can produce GI symptoms. Co-administration of ondansetron significantly reduced peak nausea and GI side effects, compared with placebo. PMID- 22298740 TI - The effects of remoxipride and chlorpromazine on eye movements and psychomotor performance in healthy volunteers. AB - Fifteen healthy male volunteers received single doses of 100 mg immediate release remoxipride (IR), 150 mg controlled release remoxipride (CR), 50 mg chlorpromazine (CPZ), 2 mg lorazepam (LZ), and placebo in a randomised, five period cross-over study. Both saccadic (SEM) and smooth pursuit eye movements (SPEM) as well as a battery of psychomotor performance tests were assessed at 1.5 h intervals over 9 h following drug administration. The areas under the response time curves and the maximum effect during the study period were analysed by analysis of variance. The most consistent impairments were produced by LZ. The neuroleptics caused impairments to SEM, and tended to impair critical flicker fusion, continuous attention and both paced and unpaced versions of the digit symbol substitution test as well as subjective measures of sedation. Only LZ impaired SPEM. Neither paced nor unpaced psychomotor tests distinguished between neuroleptics and benzodiazepines. The low therapeutic doses of IR and CR produced similar impairments to a sub-therapeutic dose of CPZ. Selectivity of pharmacological action does not appear to predict selectivity of effect on psychomotor function. PMID- 22298741 TI - Atypical antipsychotic drugs in the treatment of manic syndromes in patients with HIV-1 infection. AB - We report four people with human immunodeficiency virus (HIV) infection and mania whose manic symptoms improved when given the atypical antipsychotic agent remoxipride as an adjunct, and in whom traditional neuroleptics were not well tolerated due to marked extrapyramidal side effects. General issues surrounding choice of pharmacological agent in HIV-related mania are discussed. PMID- 22298742 TI - Is the 'A' in atypical really due to alpha2-adrenoceptor antagonism? A comment on: Putting the 'A' in atypical: does alpha2-adrenoceptor antagonism account for the therapeutic advantage of new antipsychotics? PMID- 22298743 TI - Winter workshop on schizophrenia, les diablerets, Switzerland, january 1994. PMID- 22298744 TI - Unmarried Boomers confront old age: a national portrait. AB - PURPOSE OF THE STUDY: Our study provides a national portrait of the Baby Boom generation, paying particular attention to the heterogeneity among unmarried Boomers and whether it operates similarly among women versus men. DESIGN AND METHODS: We used the 1980, 1990, and 2000 Census 5% samples and the 2009 American Community Survey (ACS) to document the trends in the share and marital status composition of the unmarried population during midlife. Using the 2009 ACS, we developed a sociodemographic portrait of Baby Boomers according to marital status. RESULTS: One in three Baby Boomers was unmarried. The vast majority of these unmarried Boomers were either divorced or never-married; just 10% were widowed. Unmarried Boomers faced greater economic, health, and social vulnerabilities compared to married Boomers. Divorced Boomers had more economic resources and better health than widowed and never-married Boomers. Widows appeared to be the most disadvantaged among Boomer women, whereas never-marrieds were the least advantaged among Boomer men. IMPLICATIONS: The rise in unmarrieds at midlife leaves Baby Boomers vulnerable to the vagaries of aging. Health care and social service providers as well as policy makers must recognize the various risk profiles of different unmarried Boomers to ensure that all Boomers age well and that society is able to provide adequate services to all Boomers, regardless of marital status. PMID- 22298745 TI - Baby Boom caregivers: care in the age of individualization. AB - PURPOSE: Many Baby Boomers are faced with the care of aging parents, as well as that of disabled or ill spouses or children. This study examines how Baby Boomers in Quebec, Canada, perceive and play their role as caregivers and how this might differ from their parents' generation. DESIGN AND METHODS: This was a qualitative and empirical study using an interpretive constructivist design. We interviewed 39 Baby Boomers caring for a family member with a semistructured guide that examined respondents' identification with their social generation, their relationship to and values regarding caregiving, and the reality of the caregiving they offered. RESULTS: In contrast to our perceptions of previous generations, the majority of interviewees refuse to be confined to the sole identity of caregiver, as they work to juggle caregiving, work, family, and social commitments. To succeed in this juggling act, they have high expectations of support from services. Based on this new approach to caregiving, we advance the idea of a "denaturalization" of care, no longer seen as a "natural" destiny or "normal" family responsibility. IMPLICATIONS: The new conception of caregiving as work that can and should be shared with services is in direct opposition to public policy that is based on the assumption of family care as the cornerstone of long-term care. Can the healthcare system adapt to the new expectations of the Baby Boom generation or will these caregivers be forced to take on elements of caregiving they no longer consider legitimate? PMID- 22298746 TI - Out of the closet and into the trenches: gay male Baby Boomers, aging, and HIV/AIDS. AB - Regardless of HIV status, all gay male Baby Boomers are aging in a context strongly shaped by HIV/AIDS. For this subcohort within the Baby Boom generation, the disproportionately high volume of AIDS deaths among gay men aged 25-44 years at the epidemic's peak (1987-1996) created a cohort effect, decimating their social networks and shaping their personal and social lives during the epidemic, throughout their life course, and into later years. But despite these lasting effects on an entire cohort of gay men, relevant scholarship narrowly focuses on older HIV-positive gay men using clinical, psychological, and social network approaches. It thus makes inadequate use of the life course perspective, which, by attention to timing, agency, and interdependence, can uncover the myriad interlocking and longitudinal aspects of the epidemic that affect this group. This article argues for the application of this latter approach to research into the lasting impacts of HIV/AIDS on this cohort of gay men. We examine HIV/AIDS mortality within this cohort at the epidemic's height, these deaths' concentration in urban gay communities, and the growing and increasingly diverse population of HIV-positive gay men born in the Baby Boom Years. Our conclusion suggests that a fuller examination of the role of HIV/AIDS in the lives of gay male Baby Boomers, using a life course perspective, is critical to appreciating this generation's heterogeneity and to expanding knowledge of how later life is shaped by the intersection between historical events, personal biography, and social and community ties. PMID- 22298747 TI - Cohort differences in the availability of informal caregivers: are the Boomers at risk? AB - PURPOSE OF THE STUDY: We compare the close family resources of Baby Boomers (BBs) to previous cohorts of older adults at population level and then examine individual-level cohort comparisons of age-related trajectories of informal care availability from midlife into old age. DESIGN AND METHODS: Population data from the U.S. Census and from the Health and Retirement Study (HRS) are used to identify a cohort similar to the BBs on marital status and fertility rates. Using generalized linear mixed models and 10-year longitudinal data from Depression and WWII parents (DWP; n = 1,052) and the parents of BBs (PBB; n = 3,573) in the HRS, we examine cohort differences in the time-varying likelihoods of being married and of having an adult child living within 10 miles. RESULTS: The DWP had similar informal care resources at entry to old age as is expected in the BB. Longitudinal analyses of the DWP and PBB cohorts in HRS reveal that the availability of family changes over time and that the DWP cohort was significantly less likely to have a spouse or a grown child living nearby. IMPLICATIONS: These findings, and future projections based on them, have significant implications for institutions and public policy concerned with the informal caregiving needs of the Boomer cohort as they age. PMID- 22298750 TI - Ethyl pyruvate improves healing of colonic anastomosis in a rat model of peritonitis. AB - BACKGROUND: This study was designed to evaluate the effects of ethyl pyruvate (EP) on wound healing in primary colonic anastomoses in intraperitoneal sepsis. METHODS: Standard left colon resection and end-to-end anastomosis were performed on 30 rats. They were grouped as control (C)--no further treatment; sepsis (S)- received 2 mL Escherichia coli (ATCC 25922) intraperitoneally (IP), and after 5 hours, standard resection and anastomosis were performed; or sepsis-group treated with EP (S-EP)--received 2 mL E coli IP, after 5 hours, standard resection and anastomosis were performed and treated with EP 50 mg/kg IP for 7 days. On the postoperative day 7, the animals were sacrificed. RESULTS: The anastomosis bursting pressure in group S was significantly lower than in the other groups. There were no differences between groups C and S-EP. Tissue hydroxyproline concentrations in group C were significantly higher than in group S. CONCLUSIONS: EP administration prevented intraperitoneal sepsis-induced impaired anastomotic healing of colon. PMID- 22298751 TI - Effect of basic laparoscopic skills courses on essential knowledge of equipment. AB - BACKGROUND: This study aims to evaluate the effect of laparoscopic skills courses on the knowledge of laparoscopic equipment. METHODS: A knowledge test on laparoscopic equipment was developed, and participants of 3 separate basic laparoscopic skills courses in the Netherlands completed the test at the beginning and end of these courses. All lectures and demonstrations during the courses were recorded on video to assess the matching of its contents with the items in the test. As a reference, the test was also completed by a group of laparoscopic experts by e-mail. RESULTS: In total, 36 participants (64.3%) completed both the pretest and posttest. Overall, the mean test score improved from 60.4% of the maximum possible score for the pretest to 68.4% for the posttest. There were no significant differences in test scores between the 3 separate courses. However, the actual content varied among the courses. The correspondence of the test items with the course content varied from 47% to 69%. Although 30% of the participants had already received training for laparoscopic equipment in their own hospital, 92.5% wanted to receive more training. 28 experts completed the test with a mean score of 75.7%, which was significantly better than the posttest score of the course participants. CONCLUSIONS: The laparoscopic skills courses evaluated in this study had a modest positive effect on the acquisition of knowledge about laparoscopic equipment. Variance exists among their contents. PMID- 22298752 TI - Laparoscopic radical nephrectomy under near real-time three-dimensional surgical navigation with C-arm cone beam computed tomography. AB - OBJECTIVE: The aim of this study was to demonstrate the advantages of C-arm cone beam computed tomography for imaging guidance of laparoscopic radical nephrectomy (LRN). METHODS: Four patients referred to the authors' institution for LRN were included in this study. To visualize the renal vascular anatomy, the Iopamiron 300 contrast agent was injected intravenously. The surgeon could adjust the viewing angle of the images and rotate the reconstructed three-dimensional (3D) image manually by using a mouse-like controller. Using the near real-time 3D navigation images, the surgeon was able to recognize the renal vascular anatomy, and more easily perform the LRN. RESULTS: All procedures were successfully performed with a satisfactory diagnostic yield or therapeutic effect without procedure-related complications. CONCLUSION: This novel technology has great potential for application in LRN because it enables accurate depiction of the renal vessels and increases surgeon confidence. PMID- 22298753 TI - Laparoscopic surgery in the management of hypersplenism and esophagogastric varices: our initial experiences. AB - BACKGROUND: Owing to recent advances in laparoscopic surgery, devascularization of the upper stomach with splenectomy (Spx) or Hassab's procedure (Has) as well as Spx for patients with portal hypertension have been attempted laparoscopically in some facilities, the results of which have been reported. This article describes the authors' surgical techniques and their results. METHODS: Between August 1999 and August 2010, the authors treated 110 cases of portal hypertension with Spx or Has. Among these patients, 56 who simultaneously underwent additional major operations were eliminated from the study, leaving 54 patients eligible. They included 38 with open surgeries and 16 with laparoscopic surgeries, which consisted of 10 splenectomies and 6 Has operations. The perioperative data for the 2 groups were compared. RESULTS: Purely laparoscopic Spx (L-Spx) was completed for 9 patients. Conversion from laparoscopic to hand-assisted laparoscopic surgery (HALS) was necessary for 1 patient because of poor visualization. Operative time was significantly longer in L-Spx than in the open method. Postoperative hospital stays were shorter for L-Spx. HALS was used for all 6 laparoscopic Has patients. There was no conversion from the laparoscopic to the open method. Operative time was significantly longer for laparoscopic Has than for open Has. Postoperative complication rates were significantly reduced, and postoperative hospital stays were significantly shorter for laparoscopic Has. CONCLUSIONS: Although the data are still preliminary, laparoscopic surgery for patients with portal hypertension may prove to be a successful strategy. PMID- 22298754 TI - The "AMID" hernia and skin stapler for Lichtenstein hernia repair: a pilot study. AB - BACKGROUND: The Lichtenstein hernia repair is a widely accepted and durable treatment option for groin hernias, but acute and chronic postoperative pain for inguinal hernia repair remains a significant issue. The aim of this study was to demonstrate the benefit of a novel hernia stapler on acute postoperative pain after a Lichtenstein hernia repair. METHODS: A prospective double-arm single center trial was conducted. Nine patients underwent a Lichtenstein hernia repair using the AMID Stapler (group 1), and another 9 patients underwent a sutured Lichtenstein hernia repair (group 2). Preoperative and postoperative pain was measured on a visual analogue scale (VAS). The intraoperative pain management was either local with sedation, spinal, or general anesthesia. All patients received a local anesthesia preemptively independent of the main anesthetic method. Medication usage, pain, and any procedure related adverse event were documented on postoperative days 1, 2, 3, 4, 5, 6, 7, and 30. RESULTS: There was no significant difference in demographic data, type or size of hernia, or in baseline pain severity between groups. No intraoperative or postoperative complications occurred. The VAS cumulative average (+/-standard deviation) pain score during the first postoperative week was 126 (+/-9.3) and 162 (+/-9.4) in group 1 and group 2, respectively (P = .38). Patients in group 1 took significantly less pain medication on days 1, 2, and 3 (P < .0001, P = .004, P = .02, respectively), and there was a trend toward a lower average analgesic demand during the entire first postoperative week: 11 (+/-0.54) doses in group 1 and 15.4 (+/-0.18) doses in group 2 (P = .07). CONCLUSION: The Lichtenstein hernia repair using the AMID Stapler is simple and safe and resulted in lower acute postoperative pain and lower analgesic consumption as compared with the sutured Lichtenstein hernia repair. A multicenter clinical trial with a large sample size is needed to more accurately study pain reduction. PMID- 22298755 TI - Development and validation of a stability-indicating RP-UPLC method for the quantitative analysis of nabumetone in tablet dosage form. AB - High efficiency and less run time are the basic requirements of high-speed chromatographic separations. To fulfill these requirements, a new separation technique, ultra-performance liquid chromatography (UPLC), has shown promising developments. A rapid, specific, sensitive, and precise reverse-phase UPLC method is developed for the determination of nabumetone in tablet dosage form. In this work, a new isocratic chromatographic method is developed. The newly developed method is applicable for assay determination of the active pharmaceutical ingredient. The chromatographic separation is achieved on a Waters Acquity BEH column (100 mm, i.d., 2.1 mm, 1.7 um) within a short runtime of 2 min using a mobile phase of 5 mM ammonium acetate-acetonitrile (25:75, v/v), at a flow rate of 0.3 mL/min at an ambient temperature. Quantification is achieved with photodiode array detection at 230 nm, over the concentration range of 0.05-26 ug/mL. Forced degradation studies are also performed for nabumetone bulk drug samples to demonstrate the stability-indicating power of the UPLC method. Comparison of system performance with conventional high-performance liquid chromatography is made with respect to analysis time, efficiency, and sensitivity. The method is validated according to the ICH guidelines and is applied successfully for the determination of nabumetone in tablets. PMID- 22298756 TI - On-line sample cleanup and enrichment chromatographic technique for the determination of ambroxol in human serum. AB - A sensitive and efficient on-line clean up and pre-concentration method has been developed using column-switching technique and protein-coated u-Bondapak CN silica pre-column for quantification of ambroxol (AM) in human serum. The method is performed by direct injection of serum sample onto a protein-coated u-Bondapak CN silica pre-column, where AM is pre-concentrated and retained, while proteins and very polar constituents are washed to waste using a phosphate buffer saline (pH 7.4). The retained analyte on the pre-column is directed onto a C(18) analytical column for separation, with a mobile phase consisting of a mixture of methanol and distilled deionized water (containing 1% triethylamine adjusted to pH 3.5 with ortho-phosphoric acid) in the ratio of 50:50 (v/v). Detection is performed at 254 nm. The calibration curve is linear over the concentration range of 12-120 ng/mL (r(2) = 0.9995). The recovery, selectivity, linearity, precision, and accuracy of the method are convenient for pharmacokinetic studies or routine assays. PMID- 22298757 TI - Determination of vitamin E isomers of grape seeds by high-performance liquid chromatography-UV detection. AB - A simple analytical method for the determination of vitamin E isomers in grape seeds by reversed-phase high-performance liquid chromatography with UV detection is described. The method is based on a solid-liquid extraction separation on an ODS column, and the analytes are monitored at 295 nm with a UV detector. Tocopherols are extracted in n-hexane and directly injected onto the column without using any purification step, such as saponification, prior to the separation and determination. The chromatographic separation of tocopherols is achieved in 12 min with a mobile phase that consists of n-hexane and isopropyl alcohol (99.99:0.01, v/v). The method is reproducible and accurate, with respect to demonstrating a relative standard deviation between 2.57% and 3.30% (n = 10, for 500 ng/mL) and a relative error between 0.84% and 6.54% (n = 10, for 500 ng/mL), respectively. The theoretical limits are estimated as 25 ng/mL for alpha tocopherol, 43 ng/mL for gamma-tocopherol, and 83 ng/mL for delta-tocopherols. The method is then applied for the determination of tocopherols in grape seeds grown in Turkey. The amounts of tocopherols are calculated by using the standard addition method. PMID- 22298758 TI - Determination of trace vitamin C by ion-pair HPLC with UV detection in calcium gluconate and vitamin C compound oral solution. AB - A sensitive and specific reversed-phase high-performance liquid chromatographic method with ultraviolet detection was developed for the determination of vitamin C, using tetrabutylammonium hydroxide as an ion-pair reagent in a compound oral solution containing 100 mg/mL calcium gluconate and 1.25 mg/mL vitamin C. The aqueous phase contained 0.005 mol/L tetrabutylammonium hydroxide and the mobile phase consisted of a mixture of the aqueous phase-methanol (80:20, v/v, pH 6.0 adjusted by phosphoric acid). The linearity, sensitivity and specificity, accuracy, and stability of the procedure were evaluated. The calibration curves for vitamin C were linear in the range of 10.0-100.0 ug/mL. The percentage coefficient of variation of the quantitative analysis of the vitamin C in the products analysis was within 5%. The method was successfully applied to determine the stability of vitamin C in the compound oral solution. It was found that the vitamin C peak was symmetrical and the column efficiency was high. The method is simple and suitable for stability testing of a low concentration of vitamin C preparation. PMID- 22298759 TI - Simultaneous HPLC-UV determination of ketamine, xylazine, and midazolam in canine plasma. AB - An isocratic reversed-phase high-performance liquid chromatography method with UV detection is developed and validated for the simultaneous determination of ketamine, xylazine, and midazolam in canine plasma. Analytes are extracted from alkalinized samples into diethyl ether-methylene chloride (7:3, v:v) using single step liquid-liquid extraction. Chromatographic separation is performed on a C(18) column using a mobile phase containing an acetonitrile-methanol-10 mM sodium heptanesulfonate buffer adjusted to pH 3, with glacial acetic acid (44:10:46, v:v) at a detection wavelength of 210 nm, with a total runtime of 10 min. The calibration is linear over the range of 78.125-5000 ng/mL for ketamine and 15.625 1000 ng/mL for xylazine and midazolam. The limits of detection are 17.8, 10.3, and 15.1 ng/mL for ketamine, xylazine, and midazolam, respectively. The extraction recoveries are 76.1% for ketamine, 91.0% for midazolam, and 78.2% for xylazine. The method is successfully used for clinical and pharmacokinetic studies of the three-drug fixed dose combination formulations. PMID- 22298760 TI - Validation of an LC method to determine skin retention profile of genistein from nanoemulsions incorporated in hydrogels. AB - Recent studies have shown the effect of soy isoflavones in preventing skin photoaging and photocarcinogenesis, especially for genistein (GEN). Nanoemulsions have been proposed as a delivery system for GEN administration due to the low water solubility of this isoflavone. This article describes the validation of an isocratic liquid chromatography method to determine GEN in porcine ear skin layers from nanoemulsions before and after incorporation into hydrogels. The analyses are performed on a reversed-phase C18 column using a mobile phase composed of methanol-water (70:30, v/v) under acid conditions (at pH 3.0) and UV detection at 270 nm. The method is linear in the range of 0.1-10 ug/mL (r(2) > 0.999) in the presence of skin extracts. The low limit of quantitation is estimated as 0.1 ug/mL. No interferences from formulation excipients or skin layer compounds are detected. The RSD values for intra- and inter-day precision are lower than 15%. Recovery ranged from approximately 90% to 110%. The method is applied to estimate GEN retention in the skin from formulations using Franz diffusion cells. The highest amount of GEN is detected in the epidermis (185 ug/cm(2)). In conclusion, the method proved to be specific, precise, and accurate in determining GEN amounts from formulations in skin retention studies. PMID- 22298761 TI - Quantification of glutathione in plasma samples by HPLC using 4-fluoro-7 nitrobenzofurazan as a fluorescent labeling reagent. AB - A rapid and highly sensitive high-performance liquid chromatograpy method with fluorescence detection has been developed for determination of glutathione (GSH) in human plasma. A simple pre-column derivatization procedure with 7-flouro-4 nitrobenzo-2-oxa-1,3-diazole (NBD-F) reagent was employed. The separation of the derivatized glutathione was performed using a mobile phase consisting of phosphate buffer (0.02 mol/L, pH 6.0)-acetonitrile (77:23, v/v) at a flow rate of 1.0 mL/min with the column temperature 2 degrees C. The eluted derivatives were fluorometrically detected at an excitation wavelength 470 nm and an emission wavelength 530 nm. Under the optimum chromatographic conditions, the calibration curve was linear over the range of 0.1 umol/L to 10.0 umol/L with the correlation coefficient of 0.9988. The precision of the method was satisfactory with the intra- and inter-day coefficient of variation being 6.3%, 6.9%, respectively. This method has been used to determine glutathione concentrations in plasma samples from healthy individuals. PMID- 22298762 TI - Development of three end-capped para-benzoyl calix[4,6, or 8]arene bonded stationary phases for HPLC. AB - Three end-capped para-benzoyl calixarene bonded silica gel stationary phases are prepared and characterized by elemental analysis, infrared spectroscopy, and thermal analysis. The comparison and selectivity of these phases are investigated by using PAHs, disubstituted benezene, and naphthalene positional isomers as probes. Possible separation mechanism based on the different interactions between calixarenes and analytes are discussed. The results indicate that the separation for those analytes are influenced by the supramolecular interaction including pi pi interaction, pi-electron transfer interactions, space steric hindrance, and hydrogen bonding interaction on the calixarene columns. Importantly, the aromatic probes with polar groups such as -OH, -NO(2), and -NH(2) could regulate the selectivity of calixarene-bonded stationary phases. PMID- 22298763 TI - Matrix solid-phase dispersion extraction of sulfonamides from blood. AB - Matrix solid-phase dispersion extraction was applied to the extraction of sulfadiazine, sulfamerazine, and sulfamethazine from human and animal bloods. The separation and determination of the analytes were carried out by high-performance liquid chromatography. The effects of the types of the dispersion adsorbents and elution solvents were investigated, and the highest recovery was obtained when diatomaceous earth was used as the dispersion adsorbent, while acetone was used as the elution solvent. Under the optimal conditions, the linear range for determining the sulfonamides in blood samples was 0.020-10.0 ug/mL, and the average recoveries of the three sulfonamides were higher than 87.5%. PMID- 22298764 TI - Chemometric study of retention on binary stationary phases in gas chromatography. AB - Using gas chromatography, data analysis is performed on a dataset consisting of 486 retention indices, 27 standards (ramified alkanes, aliphatic alcohols, and aromatic compounds), 6 pure and binary stationary phases, and three temperatures. The behavior of the pure stationary phases (OV-3, OV-225, OV-61-OH, and OV-1701 OH) and the binary stationary phases (OV-3/OV-225 and OV-61-OH/OV-1701-OH) at different temperatures (60 degrees C-100 degrees C) is investigated with factor and topological analysis. The influence of temperature and the nature of the mixed stationary phases on the retention indices is studied by correspondence factor analysis (CFA). The non-additivity of the retention properties of the pure phases used as mixed phases is clearly established by CFA. The topological analysis of the substituent's effect is investigated with a DARC/PELCO procedure and shows the particular influence of the stationary phase composition on the retention. The substituent effect is measured for the pure and binary stationary phases at various temperatures. The evolution of the substituent effect from the pure stationary phases to the binary phases is discussed. PMID- 22298765 TI - Determination of polychlorinated biphenyls and organochlorine pesticides in human serum by gas chromatography with micro-electron capture detector. AB - A method for determination of concentrations of polychlorinated biphenyl congeners (PCB-28, 52, 101, 118, 138, 153, 156, and 187) and organochlorine pesticides (hexachlorobenzene, alpha-hexachlorocyclohexane, beta hexachlorocyclohexane, gamma-hexachlorocyclohexane, delta-hexachlorocyclohexane, p,p'-dichlorodiphenyl dichloroethylene, o,p'-dichlorodiphenyl trichloroethane, p,p'-dichlorodiphenyl dichloroethane, p,p'-dichlorodiphenyl trichloroethane, alpha-chlordane, gamma-chlordane, heptachlor, heptachlor epoxide, and aldrin) in human serum is developed. Recovery is assessed with artificial serum, in which PCBs and OCPs could not be detected. The method is then confirmed with pooled human serum. Experiments are performed by adding two concentrations of analytes (0.5 ug/L and 1.0 ug/L) to both matrices. The sample pretreatment process involves denaturing with a mixture of water-1-propanol (v:v, 85:15), extraction with a C-18 cartridge, and cleanup with an Alumina B cartridge. This process required about 2 mL of serum. The limit of detection ranged from 0.05-0.35 ug/L for all the analytes. Recovery of analytes at low and high spiking concentrations varied from 63-122% and 61-124% for artificial serum and pooled human serum, respectively. Relative standard deviation was lower than 16% and 18% for artificial serum and pooled human serum, respectively. Stability of the method, expressed as relative standard deviation, was lower than 14%. The method has been applied in epidemiological research. PMID- 22298766 TI - Simultaneous analysis of biologically active pyridines in pharmaceutical formulations by capillary zone electrophoresis. AB - A capillary zone electrophoretic method using UV detection is developed for the analysis of four biological active pyridines [i.e., nicotine (NIC), cotinine (COT), nicotinic acid (NA), and nicotinamide (NM)]. The separation of the pyridines is achieved in 25 mM sodium dihydrogen phosphate (pH 2.1) using a fused silica capillary with an effective length of 56 cm and an inner diameter of 50 um (extended light path), hydrodynamic injection at 50 mbar for 10 s, a temperature of 25 degrees C, applied voltage of 30 kV, and UV detection at 260 nm. These conditions provide baseline separation of all the analytes [resolution (R(s)) > 3.6] in 9.4 min with good linearity (r(2) > 0.998, in ranges of 50-600 ug/mL for NIC, 8-160 ug/mL for NM, and 10-200 ug/mL for COT and NA), precision (relative standard deviation <2.04%), recovery (96.4-101.6%), limits of detection (<3.0 ug/mL), and quantitation (<10 ug/mL). The method is robust upon the alterations of pH of BGE, separating voltage, and injection time [the RSDs of the relative migration time (migration time of the analyte/migration time of the internal standard) and resolution <3.26%]. The method is efficient, reliable, and simple for the routine analysis of NIC, NA, and NM in various products such as gum and tablets and can be applied to determine COT in thermal degradation of NIC gum. PMID- 22298767 TI - Hepatic stellate cell-derived delta-like homolog 1 (DLK1) protein in liver regeneration. AB - Hepatic stellate cells (HSCs) undergo myofibroblastic activation in liver fibrosis and regeneration. This phenotypic switch is mechanistically similar to dedifferentiation of adipocytes as such the necdin-Wnt pathway causes epigenetic repression of the master adipogenic gene Ppargamma, to activate HSCs. Now we report that delta-like 1 homolog (DLK1) is expressed selectively in HSCs in the adult rodent liver and induced in liver fibrosis and regeneration. Dlk1 knockdown in activated HSCs, causes suppression of necdin and Wnt, epigenetic derepression of Ppargamma, and morphologic and functional reversal to quiescent cells. Hepatic Dlk1 expression is induced 40-fold at 24 h after partial hepatectomy (PH) in mice. HSCs and hepatocytes (HCs) isolated from the regenerating liver show Dlk1 induction in both cell types. In HC and HSC co-culture, increased proliferation and Dlk1 expression by HCs from PH are abrogated with anti-DLK1 antibody (Ab). Dlk1 and Wnt10b expression by Sham HCs are increased by co-culture with PH HSCs, and these effects are abolished with anti-DLK Ab. A tail vein injection of anti DLK1 Ab at 6 h after PH reduces early HC proliferation and liver growth, accompanied by decreased Wnt10b, nonphosphorylated beta-catenin, p-beta-catenin (Ser-552), cyclins (cyclin D and cyclin A), cyclin-dependent kinases (CDK4, and CDK1/2), p-ERK1/2, and p-AKT. In the mouse developing liver, HSC precursors and HSCs express high levels of Dlk1, concomitant with Dlk1 expression by hepatoblasts. These results suggest novel roles of HSC-derived DLK1 in activating HSCs via epigenetic Ppargamma repression and participating in liver regeneration and development in a manner involving the mesenchymal-epithelial interaction. PMID- 22298768 TI - Inducible malondialdehyde pools in zones of cell proliferation and developing tissues in Arabidopsis. AB - Malondialdehyde (MDA) is a natural and widespread genotoxin. Given its potentially deleterious effects, it is of interest to establish the identities of the cell types containing this aldehyde. We used in situ chemical trapping with 2 thiobarbituric acid and mass spectrometry with a deuterated standard to characterize MDA pools in the vegetative phase in Arabidopsis thaliana. In leaves, MDA occurred predominantly in the intracellular compartment of mesophyll cells and was enriched in chloroplasts where it was derived primarily from triunsaturated fatty acids (TFAs). High levels of MDA (most of which was unbound) were found within dividing cells in the root tip cell proliferation zone. The bulk of this MDA did not originate from TFAs. We confirmed the localization of MDA in transversal root sections. In addition to MDA in proliferating cells near the root tip we found evidence for the presence of MDA in pericyle cells. Remodeling of non-TFA-derived MDA pools occurred when seedlings were infected with the fungus Botrytis cinerea. Treatment of uninfected seedlings with mediators of plant stress responses (jasmonic acid or salicylic acid) increased seedling MDA levels over 20-fold. In summary, major pools of MDA are associated with cell division foci containing stem cells. The aldehyde is pathogen-inducible in these regions and its levels are increased by cellular mediators that impact defense and growth. PMID- 22298769 TI - Role of epithelial-stem cell interactions during dental cell differentiation. AB - Epithelial-mesenchymal interactions regulate the growth and morphogenesis of ectodermal organs such as teeth. Dental pulp stem cells (DPSCs) are a part of dental mesenchyme, derived from the cranial neural crest, and differentiate into dentin forming odontoblasts. However, the interactions between DPSCs and epithelium have not been clearly elucidated. In this study, we established a mouse dental pulp stem cell line (SP) comprised of enriched side population cells that displayed a multipotent capacity to differentiate into odontogenic, osteogenic, adipogenic, and neurogenic cells. We also analyzed the interactions between SP cells and cells from the rat dental epithelial SF2 line. When cultured with SF2 cells, SP cells differentiated into odontoblasts that expressed dentin sialophosphoprotein. This differentiation was regulated by BMP2 and BMP4, and inhibited by the BMP antagonist Noggin. We also found that mouse iPS cells cultured with mitomycin C-treated SF2-24 cells displayed an epithelial cell-like morphology. Those cells expressed the epithelial cell markers p63 and cytokeratin 14, and the ameloblast markers ameloblastin and enamelin, whereas they did not express the endodermal cell marker Gata6 or mesodermal cell marker brachyury. This is the first report of differentiation of iPS cells into ameloblasts via interactions with dental epithelium. Co-culturing with dental epithelial cells appears to induce stem cell differentiation that favors an odontogenic cell fate, which may be a useful approach for tooth bioengineering strategies. PMID- 22298770 TI - Kinetics of alpha-globin binding to alpha-hemoglobin stabilizing protein (AHSP) indicate preferential stabilization of hemichrome folding intermediate. AB - Human alpha-hemoglobin stabilizing protein (AHSP) is a conserved mammalian erythroid protein that facilitates the production of Hemoglobin A by stabilizing free alpha-globin. AHSP rapidly binds to ferrous alpha with association (k'(AHSP)) and dissociation (k(AHSP)) rate constants of ~10 MUm(-1) s(-1) and 0.2 s(-1), respectively, at pH 7.4 at 22 degrees C. A small slow phase was observed when AHSP binds to excess ferrous alphaCO. This slow phase appears to be due to cis to trans prolyl isomerization of the Asp(29)-Pro(30) peptide bond in wild type AHSP because it was absent when alphaCO was mixed with P30A and P30W AHSP, which are fixed in the trans conformation. This slow phase was also absent when met(Fe(3+))-alpha reacted with wild-type AHSP, suggesting that met-alpha is capable of rapidly binding to either Pro(30) conformer. Both wild-type and Pro(30)-substituted AHSPs drive the formation of a met-alpha hemichrome conformation following binding to either met- or oxy(Fe(2+))-alpha. The dissociation rate of the met-alpha.AHSP complex (k(AHSP) ~ 0.002 s(-1)) is ~100 fold slower than that for ferrous alpha.AHSP complexes, resulting in a much higher affinity of AHSP for met-alpha. Thus, in vivo, AHSP acts as a molecular chaperone by rapidly binding and stabilizing met-alpha hemichrome folding intermediates. The low rate of met-alpha dissociation also allows AHSP to have a quality control function by kinetically trapping ferric alpha and preventing its incorporation into less stable mixed valence Hemoglobin A tetramers. Reduction of AHSP-bound met-alpha allows more rapid release to beta subunits to form stable fully, reduced hemoglobin dimers and tetramers. PMID- 22298771 TI - Organ-specific sulfation patterns of heparan sulfate generated by extracellular sulfatases Sulf1 and Sulf2 in mice. AB - Heparan sulfate endosulfatases Sulf1 and Sulf2 hydrolyze 6-O-sulfate in heparan sulfate, thereby regulating cellular signaling. Previous studies have revealed that Sulfs act predominantly on UA2S-GlcNS6S disaccharides and weakly on UA GlcNS6S disaccharides. However, the specificity of Sulfs and their role in sulfation patterning of heparan sulfate in vivo remained unknown. Here, we performed disaccharide analysis of heparan sulfate in Sulf1 and Sulf2 knock-out mice. Significant increases in DeltaUA2S-GlcNS6S were observed in the brain, small intestine, lung, spleen, testis, and skeletal muscle of adult Sulf1(-/-) mice and in the brain, liver, kidney, spleen, and testis of adult Sulf2(-/-) mice. In addition, increases in DeltaUA-GlcNS6S were seen in the Sulf1(-/-) lung and small intestine. In contrast, the disaccharide compositions of chondroitin sulfate were not primarily altered, indicating specificity of Sulfs for heparan sulfate. For Sulf1, but not for Sulf2, mRNA expression levels in eight organs of wild-type mice were highly correlated with increases in DeltaUA2S-GlcNS6S in the corresponding organs of knock-out mice. Moreover, overall changes in heparan sulfate compositions were greater in Sulf1(-/-) mice than in Sulf2(-/-) mice despite lower levels of Sulf1 mRNA expression, suggesting predominant roles of Sulf1 in heparan sulfate desulfation and distinct regulation of Sulf activities in vivo. Sulf1 and Sulf2 mRNAs were differentially expressed in restricted types of cells in organs, and consequently, the sulfation patterns of heparan sulfate were locally and distinctly altered in Sulf1 and Sulf2 knock-out mice. These findings indicate that Sulf1 and Sulf2 differentially contribute to the generation of organ-specific sulfation patterns of heparan sulfate. PMID- 22298772 TI - Age-related changes in rat myocardium involve altered capacities of glycosaminoglycans to potentiate growth factor functions and heparan sulfate altered sulfation. AB - Glycosaminoglycans (GAGs) are essential components of the extracellular matrix, the natural environment from which cell behavior is regulated by a number or tissue homeostasis guarantors including growth factors. Because most heparin binding growth factor activities are regulated by GAGs, structural and functional alterations of these polysaccharides may consequently affect the integrity of tissues during critical physiological and pathological processes. Here, we investigated whether the aging process can induce changes in the myocardial GAG composition in rats and whether these changes can affect the activities of particular heparin-binding growth factors known to sustain cardiac tissue integrity. Our results showed an age-dependent increase of GAG levels in the left ventricle. Biochemical and immunohistological studies pointed out heparan sulfates (HS) as the GAG species that increased with age. ELISA-based competition assays showed altered capacities of the aged myocardial GAGs to bind FGF-1, FGF 2, and VEGF but not HB EGF. Mitogenic assays in cultured cells showed an age dependent decrease of the elderly GAG capacities to potentiate FGF-2 whereas the potentiating effect on VEGF(165) was increased, as confirmed by augmented angiogenic cell proliferation in Matrigel plugs. Moreover, HS disaccharide analysis showed considerably altered 6-O-sulfation with modest changes in N- and 2-O-sulfations. Together, these findings suggest a physiological significance of HS structural and functional alterations during aging. This can be associated with an age-dependent decline of the extracellular matrix capacity to efficiently modulate not only the activity of resident or therapeutic growth factors but also the homing of resident or therapeutic cells. PMID- 22298773 TI - Heparan sulfate chains of syndecan-1 regulate ectodomain shedding. AB - Matrix metalloproteinases release intact syndecan-1 ectodomains from the cell surface giving rise to a soluble, shed form of the proteoglycan. Although it is known that shed syndecan-1 controls diverse pathophysiological responses in cancer, wound healing, inflammation, infection, and immunity, the mechanisms regulating shedding remain unclear. We have discovered that the heparan sulfate chains present on syndecan core proteins suppress shedding of the proteoglycan. Syndecan shedding is dramatically enhanced when the heparan sulfate chains are enzymatically degraded or absent from the core protein. Exogenous heparan sulfate or heparin does not inhibit shedding, indicating that heparan sulfate must be attached to the core protein to suppress shedding. Regulation of shedding by heparan sulfate occurs in multiple cell types, for both syndecan-1 and syndecan-4 and in murine and human syndecans. Mechanistically, the loss of heparan sulfate enhances the susceptibility of the core protein to proteolytic cleavage by matrix metalloproteinases. Enhanced shedding of syndecan-1 following loss of heparan sulfate is accompanied by a dramatic increase in core protein synthesis. This suggests that in response to an increase in the rate of shedding, cells attempt to maintain a significant level of syndecan-1 on the cell surface. Together these data indicate that the amount of heparan sulfate present on syndecan core proteins regulates both the rate of syndecan shedding and core protein synthesis. These findings assign new functions to heparan sulfate chains, thereby broadening our understanding of their physiological importance and implying that therapeutic inhibition of heparan sulfate degradation could impact the progression of some diseases. PMID- 22298774 TI - The [corrected] SEC23-SEC31 [corrected] interface plays critical role for export of procollagen from the endoplasmic reticulum. AB - COPII proteins are essential for exporting most cargo molecules from the endoplasmic reticulum. The membrane-facing surface of the COPII proteins (especially SEC23-SEC24) interacts directly or indirectly with the cargo molecules destined for exit. As we characterized the SEC23A mutations at the SEC31 binding site identified from patients with cranio-lenticulo-sutural dysplasia, we discovered that the SEC23-SEC31 interface can also influence cargo selection. Remarkably, M702V SEC23A does not compromise COPII assembly, vesicle size, and packaging of cargo molecules into COPII vesicles that we have tested but induces accumulation of procollagen in the endoplasmic reticulum when expressed in normal fibroblasts. We observed that M702V SEC23A activates SAR1B GTPase more than wild-type SEC23A when SEC13-SEC31 is present, indicating that M702V SEC23A causes premature dissociation of COPII from the membrane. Our results indicate that a longer stay of COPII proteins on the membrane is required to cargo procollagen than other molecules and suggest that the SEC23-SEC31 interface plays a critical role in capturing various cargo molecules. PMID- 22298775 TI - FoxO1 protein cooperates with ATF4 protein in osteoblasts to control glucose homeostasis. AB - The Forkhead transcription factor FoxO1 inhibits through its expression in osteoblasts beta-cell proliferation, insulin secretion, and sensitivity. At least part of the FoxO1 metabolic functions result from its ability to suppress the activity of osteocalcin, an osteoblast-derived hormone favoring glucose metabolism and energy expenditure. In searching for mechanisms mediating the metabolic actions of FoxO1, we focused on ATF4, because this transcription factor also affects glucose metabolism through its expression in osteoblasts. We show here that FoxO1 co-localizes with ATF4 in the osteoblast nucleus, and physically interacts with and promotes the transcriptional activity of ATF4. Genetic experiments demonstrate that FoxO1 and ATF4 cooperate to increase glucose levels and decrease glucose tolerance. These effects result from a synergistic effect of the two transcription factors to suppress the activity of osteocalcin through up regulating expression of the phosphatase catalyzing osteocalcin inactivation. As a result, insulin production by beta-cells and insulin signaling in the muscle, liver and white adipose tissue are compromised and fat weight increases by the FoxO1/ATF4 interaction. Taken together these observations demonstrate that FoxO1 and ATF4 cooperate in osteoblasts to regulate glucose homeostasis. PMID- 22298776 TI - Insights into mechanism of glucokinase activation: observation of multiple distinct protein conformations. AB - Human glucokinase (GK) is a principal regulating sensor of plasma glucose levels. Mutations that inactivate GK are linked to diabetes, and mutations that activate it are associated with hypoglycemia. Unique kinetic properties equip GK for its regulatory role: although it has weak basal affinity for glucose, positive cooperativity in its binding of glucose causes a rapid increase in catalytic activity when plasma glucose concentrations rise above euglycemic levels. In clinical trials, small molecule GK activators (GKAs) have been efficacious in lowering plasma glucose and enhancing glucose-stimulated insulin secretion, but they carry a risk of overly activating GK and causing hypoglycemia. The theoretical models proposed to date attribute the positive cooperativity of GK to the existence of distinct protein conformations that interconvert slowly and exhibit different affinities for glucose. Here we report the respective crystal structures of the catalytic complex of GK and of a GK-glucose complex in a wide open conformation. To assess conformations of GK in solution, we also carried out small angle x-ray scattering experiments. The results showed that glucose dose dependently converts GK from an apo conformation to an active open conformation. Compared with wild type GK, activating mutants required notably lower concentrations of glucose to be converted to the active open conformation. GKAs decreased the level of glucose required for GK activation, and different compounds demonstrated distinct activation profiles. These results lead us to propose a modified mnemonic model to explain cooperativity in GK. Our findings may offer new approaches for designing GKAs with reduced hypoglycemic risk. PMID- 22298777 TI - Characterization of heparin-binding site of tissue transglutaminase: its importance in cell surface targeting, matrix deposition, and cell signaling. AB - Tissue transglutaminase (TG2) is a multifunctional Ca(2+)-activated protein cross linking enzyme secreted into the extracellular matrix (ECM), where it is involved in wound healing and scarring, tissue fibrosis, celiac disease, and metastatic cancer. Extracellular TG2 can also facilitate cell adhesion important in wound healing through a nontransamidating mechanism via its association with fibronectin, heparan sulfates (HS), and integrins. Regulating the mechanism how TG2 is translocated into the ECM therefore provides a strategy for modulating these physiological and pathological functions of the enzyme. Here, through molecular modeling and mutagenesis, we have identified the HS-binding site of TG2 (202)KFLKNAGRDCSRRSSPVYVGR(222). We demonstrate the requirement of this binding site for translocation of TG2 into the ECM through a mechanism involving cell surface shedding of HS. By synthesizing a peptide NPKFLKNAGRDCSRRSS corresponding to the HS-binding site within TG2, we also demonstrate how this mimicking peptide can in isolation compensate for the RGD-induced loss of cell adhesion on fibronectin via binding to syndecan-4, leading to activation of PKCalpha, pFAK 397, and ERK1/2 and the subsequent formation of focal adhesions and actin cytoskeleton organization. A novel regulatory mechanism for TG2 translocation into the extracellular compartment that depends upon TG2 conformation and the binding of HS is proposed. PMID- 22298778 TI - cAMP induces stromal interaction molecule 1 (STIM1) puncta but neither Orai1 protein clustering nor store-operated Ca2+ entry (SOCE) in islet cells. AB - The events leading to the activation of store-operated Ca(2+) entry (SOCE) involve Ca(2+) depletion of the endoplasmic reticulum (ER) resulting in translocation of the transmembrane Ca(2+) sensor protein, stromal interaction molecule 1 (STIM1), to the junctions between ER and the plasma membrane where it binds to the Ca(2+) channel protein Orai1 to activate Ca(2+) influx. Using confocal and total internal reflection fluorescence microscopy, we studied redistribution kinetics of fluorescence-tagged STIM1 and Orai1 as well as SOCE in insulin-releasing beta-cells and glucagon-secreting alpha-cells within intact mouse and human pancreatic islets. ER Ca(2+) depletion triggered accumulation of STIM1 puncta in the subplasmalemmal ER where they co-clustered with Orai1 in the plasma membrane and activated SOCE. Glucose, which promotes Ca(2+) store filling and inhibits SOCE, stimulated retranslocation of STIM1 to the bulk ER. This effect was evident at much lower glucose concentrations in alpha- than in beta cells consistent with involvement of SOCE in the regulation of glucagon secretion. Epinephrine stimulated subplasmalemmal translocation of STIM1 in alpha cells and retranslocation in beta-cells involving raising and lowering of cAMP, respectively. The cAMP effect was mediated both by protein kinase A and exchange protein directly activated by cAMP. However, the cAMP-induced STIM1 puncta did not co-cluster with Orai1, and there was no activation of SOCE. STIM1 translocation can consequently occur independently of Orai1 clustering and SOCE. PMID- 22298779 TI - Bivalent carbohydrate binding is required for biological activity of Clitocybe nebularis lectin (CNL), the N,N'-diacetyllactosediamine (GalNAcbeta1-4GlcNAc, LacdiNAc)-specific lectin from basidiomycete C. nebularis. AB - Lectins are carbohydrate-binding proteins that exert their biological activity by binding to specific cell glycoreceptors. We have expressed CNL, a ricin B-like lectin from the basidiomycete Clitocybe nebularis in Escherichia coli. The recombinant lectin, rCNL, agglutinates human blood group A erythrocytes and is specific for the unique glycan N,N'-diacetyllactosediamine (GalNAcbeta1-4GlcNAc, LacdiNAc) as demonstrated by glycan microarray analysis. We here describe the crystal structures of rCNL in complex with lactose and LacdiNAc, defining its interactions with the sugars. CNL is a homodimeric lectin, each of whose monomers consist of a single ricin B lectin domain with its beta-trefoil fold and one carbohydrate-binding site. To study the mode of CNL action, a nonsugar-binding mutant and nondimerizing monovalent CNL mutants that retain carbohydrate-binding activity were prepared. rCNL and the mutants were examined for their biological activities against Jurkat human leukemic T cells and the hypersensitive nematode Caenorhabditis elegans mutant strain pmk-1. rCNL was toxic against both, although the mutants were inactive. Thus, the bivalent carbohydrate-binding property of homodimeric CNL is essential for its activity, providing one of the rare pieces of evidence that certain activities of lectins are associated with their multivalency. PMID- 22298780 TI - Extreme C terminus of bacterial cytoskeletal protein FtsZ plays fundamental role in assembly independent of modulatory proteins. AB - Bacterial cell division typically requires assembly of the cytoskeletal protein FtsZ into a ring (Z-ring) at the nascent division site that serves as a foundation for assembly of the division apparatus. High resolution imaging suggests that the Z-ring consists of short, single-stranded polymers held together by lateral interactions. Several proteins implicated in stabilizing the Z-ring enhance lateral interactions between FtsZ polymers in vitro. Here we report that residues at the C terminus of Bacillus subtilis FtsZ (C-terminal variable region (CTV)) are both necessary and sufficient for stimulating lateral interactions in vitro in the absence of modulatory proteins. Swapping the 6 residue CTV from B. subtilis FtsZ with the 4-residue CTV from Escherichia coli FtsZ completely abolished lateral interactions between chimeric B. subtilis FtsZ polymers. The E. coli FtsZ chimera readily formed higher order structures normally seen only in the presence of molecular crowding agents. CTV-mediated lateral interactions are important for the integrity of the Z-ring because B. subtilis cells expressing the B. subtilis FtsZ chimera had a low frequency of FtsZ ring formation and a high degree of filamentation relative to wild-type cells. Site-directed mutagenesis of the B. subtilis CTV suggests that electrostatic forces are an important determinant of lateral interaction potential. PMID- 22298781 TI - alpha-Catenin inhibits beta-catenin-T-cell factor/lymphoid enhancing factor transcriptional activity and collagen type II expression in articular chondrocytes through formation of Gli3R.alpha-catenin.beta-catenin ternary complex. AB - Chondrocytes, a unique cell type in cartilage tissue, are responsible for the regulation of anabolic and catabolic homeostasis in cartilage-specific extracellular matrix synthesis. Activation of Wnt/beta-catenin signaling induces dedifferentiation of articular chondrocytes, resulting in suppression of type II collagen expression. We have shown previously that alpha-catenin inhibits beta catenin-Tcf/Lef (T-cell factor/lymphoid-enhancing factor) transcriptional activity in articular chondrocytes with a concomitant recovery of type II collagen expression. In the current study, we elucidated the mechanism underlying this inhibition of beta-catenin-Tcf/Lef transcriptional activity by alpha catenin, showing that it requires direct interaction between alpha-catenin and beta-catenin. We further showed that it involves recruitment of Gli3R, the short transcription-repressing form of the transcription factor Gli3, to beta-catenin by alpha-catenin. The resulting inhibition of beta-catenin transcriptional activity leads to increased expression of type II collagen. Gli3R and alpha catenin actions are co-dependent: both are necessary for the observed inhibitory effects on beta-catenin transcriptional activity. Reducing Gli3R expression levels through activation of Indian Hedgehog (Ihh) signaling also is sufficient to activate beta-catenin transcriptional activity, suggesting that the ternary complex, Gli3R.alpha-catenin.beta-catenin, mediates Ihh-dependent activation of Wnt/beta-catenin signaling in articular chondrocytes. Collectively, this study shows that alpha-catenin functions as a nuclear factor that recruits the transcriptional repressor Gli3R to beta-catenin to inhibit beta-catenin transcriptional activity and dedifferentiation of articular chondrocytes. Finally, osteoarthritic cartilage showed elevated levels of beta-catenin and decreased levels of alpha-catenin and Gli3R, suggesting that decreased levels of alpha-catenin and Gli3R levels contribute to increased beta-catenin transcriptional activity during osteoarthritic cartilage destruction. PMID- 22298782 TI - P2Y2 receptor-mediated lymphotoxin-alpha secretion regulates intercellular cell adhesion molecule-1 expression in vascular smooth muscle cells. AB - The proinflammatory cytokine lymphotoxin-alpha (LTA) is thought to contribute to the pathogenesis of atherosclerosis. However, the mechanisms that regulate its expression in vascular smooth muscle cells (VSMC) are poorly understood. The ability of exogenous nucleotides to stimulate LTA production was evaluated in VSMC by ELISA. The P2Y(2) nucleotide receptor (P2Y(2)R) agonist UTP stimulates a strong and sustained release of LTA from WT but not P2Y(2)R(-/-) SMC. Assessment of LTA gene transcription by LTA promoter-luciferase construct indicated that LTA levels are controlled at the level of transcription. We show using RNAi techniques that knockdown of the actin-binding protein filamin-A (FLNa) severely impaired nucleotide-induced Rho activation and consequent Rho-mediated LTA secretion. Reintroduction of FLNa in FLNa RNAi SMC rescued UTP-induced LTA expression. In addition, we found that UTP-stimulated LTA secretion is not sensitive to brefeldin A, which blocks the formation of vesicles involved in protein transport from the endoplasmic reticulum to the Golgi apparatus, suggesting that P2Y(2)R/filamin-mediated secretion of LTA is independent of the endoplasmic reticulum/Golgi secretory vesicle route. Furthermore, UTP selectively induces ICAM-1 expression in WT but not SMC expressing a truncated P2Y(2)R deficient in LTA secretion. These data suggest that P2Y(2)R recruits FLNa to provide a cytoskeletal scaffold necessary for Rho signaling pathway upstream of LTA release and subsequent stimulation of ICAM-1 expression on vascular smooth muscle cells. PMID- 22298783 TI - Function of transient receptor potential cation channel subfamily V member 4 (TRPV4) as a mechanical transducer in flow-sensitive segments of renal collecting duct system. AB - The TRPV4 Ca(2+)-permeable channel is sensitive to mechanical stimuli. In the current study we have employed immunocytochemical staining in kidney slices and functional assessments (Ca(2+) imaging) in isolated, split-opened, tubule segments to define TRPV4 sites of expression and flow-dependent function in the collecting duct system. Staining patterns revealed strong expression of TRPV4 along the entire collecting duct system with highest levels at the apical (luminal)/subapical region of the principal cells (PCs), the dominant cell type, with more diffuse staining in intercalated cells (ICs). Using fluorescence Ca(2+) imaging and the selective TRPV4 agonist, GSK1016790A, we demonstrated functional TRPV4 channels in PCs and ICs of split-opened cortical collecting ducts and connecting tubules. The agonist was ineffective in inducing a rise in [Ca(2+)](i) in the absence of extracellular Ca(2+) or in tubules from TRPV4-deficient animals. Most importantly, a 10-fold elevation in luminal (apical) fluid flow induced a rapid and sustained influx of Ca(2+) that was abolished by the TRPV channel inhibitor, ruthenium red, or in tubules isolated from TRPV4 deficient animals. We concluded that TRPV4 is highly expressed along the entire collecting duct system where it appears to function as a sensor/transducer of flow-induce mechanical stresses. PMID- 22298784 TI - Piceatannol, natural polyphenolic stilbene, inhibits adipogenesis via modulation of mitotic clonal expansion and insulin receptor-dependent insulin signaling in early phase of differentiation. AB - Piceatannol, a natural stilbene, is an analog and a metabolite of resveratrol. Despite a well documented health benefit of resveratrol in intervention of the development of obesity, the role of piceatannol in the development of adipose tissue and related diseases is unknown. Here, we sought to determine the function of piceatannol in adipogenesis and elucidate the underlying mechanism. We show that piceatannol inhibits adipogenesis of 3T3-L1 preadipocytes in a dose dependent manner at noncytotoxic concentrations. This anti-adipogenic property of piceatannol was largely limited to the early event of adipogenesis. In the early phase of adipogenesis, piceatannol-treated preadipocytes displayed a delayed cell cycle entry into G(2)/M phase at 24 h after initiation of adipogenesis. Furthermore, the piceatannol-suppressed mitotic clonal expansion was accompanied by reduced activation of the insulin-signaling pathway. Piceatannol dose dependently inhibited differentiation mixture-induced phosphorylation of insulin receptor (IR)/insulin receptor substrate-1 (IRS-1)/Akt pathway in the early phase of adipogenesis. Moreover, we showed that piceatannol is an inhibitor of IR kinase activity and phosphatidylinositol 3-kinase (PI3K). Our kinetics study of IR further identified a K(m) value for ATP of 57.8 MUm and a K(i) value for piceatannol of 28.9 MUm. We also showed that piceatannol directly binds to IR and inhibits IR kinase activity in a mixed noncompetitive manner to ATP, through which piceatannol appears to inhibit adipogenesis. Taken together, our study reveals an anti-adipogenic function of piceatannol and highlights IR and its downstream insulin signaling as novel targets for piceatannol in the early phase of adipogenesis. PMID- 22298785 TI - Undersulfation of heparan sulfate restricts differentiation potential of mouse embryonic stem cells. AB - Heparan sulfate proteoglycans, present on cell surfaces and in the extracellular matrix, interact with growth factors and morphogens to influence growth and differentiation of cells. The sulfation pattern of the heparan sulfate chains formed during biosynthesis in the Golgi compartment will determine the interaction potential of the proteoglycan. The glucosaminyl N-deacetylase/N sulfotransferase (NDST) enzymes have a key role during biosynthesis, greatly influencing total sulfation of the heparan sulfate chains. The differentiation potential of mouse embryonic stem cells lacking both NDST1 and NDST2 was studied using in vitro differentiation protocols, expression of differentiation markers, and assessment of the ability of the cells to respond to growth factors. The results show that NDST1 and NDST2 are dispensable for mesodermal differentiation into osteoblasts but necessary for induction of adipocytes and neural cells. Gene expression analysis suggested a differentiation block at the primitive ectoderm stage. Also, GATA4, a primitive endoderm marker, was expressed by these cells. The addition of FGF4 or FGF2 together with heparin rescued the differentiation potential to neural progenitors and further to mature neurons and glia. Our results suggest that the embryonic stem cells lacking both NDST1 and NDST2, expressing a very low sulfated heparan sulfate, can take the initial step toward differentiation into all three germ layers. Except for their potential for mesodermal differentiation into osteoblasts, the cells are then arrested in a primitive ectoderm and/or endoderm stage. PMID- 22298786 TI - Role of metalloproteases in vaccinia virus epitope processing for transporter associated with antigen processing (TAP)-independent human leukocyte antigen (HLA)-B7 class I antigen presentation. AB - The transporter associated with antigen processing (TAP) translocates the viral proteolytic peptides generated by the proteasome and other proteases in the cytosol to the endoplasmic reticulum lumen. There, they complex with nascent human leukocyte antigen (HLA) class I molecules, which are subsequently recognized by the CD8(+) lymphocyte cellular response. However, individuals with nonfunctional TAP complexes or tumor or infected cells with blocked TAP molecules are able to present HLA class I ligands generated by TAP-independent processing pathways. Herein, using a TAP-independent polyclonal vaccinia virus-polyspecific CD8(+) T cell line, two conserved vaccinia-derived TAP-independent HLA-B*0702 epitopes were identified. The presentation of these epitopes in normal cells occurs via complex antigen-processing pathways involving the proteasome and/or different subsets of metalloproteinases (amino-, carboxy-, and endoproteases), which were blocked in infected cells with specific chemical inhibitors. These data support the hypothesis that the abundant cellular proteolytic systems contribute to the supply of peptides recognized by the antiviral cellular immune response, thereby facilitating immunosurveillance. These data may explain why TAP deficient individuals live normal life spans without any increased susceptibility to viral infections. PMID- 22298787 TI - PP6 regulatory subunit R1 is bidentate anchor for targeting protein phosphatase-6 to DNA-dependent protein kinase. AB - DNA-dependent protein kinase (DNA-PK) becomes activated in response to DNA double strand breaks, initiating repair by the non-homologous end joining pathway. DNA.PK complexes with the regulatory subunit SAPSR1 (R1) of protein phosphatase-6 (PP6). Knockdown of either R1 or PP6c prevents DNA-PK activation in response to ionizing radiation-induced DNA damage and radiosensitizes glioblastoma cells. Here, we demonstrate that R1 is necessary for and bridges the interaction between DNA-PK and PP6c. Using R1 deletion mutants, DNA-PK binding was mapped to two distinct regions of R1 spanning residues 1-326 and 522-700. Either region expressed alone was sufficient to bind DNA-PK, but only deletion of residues 1 326, not 522-700, eliminated interaction of R1 with DNA-PK. We assign 1-326 as the dominant domain and 522-700 as the supporting region. These results demonstrate that R1 acts as a bidentate anchor to DNA-PK and recruits PP6c. Targeting the dominant interface with small molecule or peptidomimetic inhibitors could specifically prevent activation of DNA-PK and thereby sensitize cells to ionizing radiation and other genotoxic agents. PMID- 22298788 TI - Two-step mechanism for modifier of transcription 1 (Mot1) enzyme-catalyzed displacement of TATA-binding protein (TBP) from DNA. AB - The TATA box binding protein (TBP) is a central component of the transcription preinitiation complex, and its occupancy at a promoter is correlated with transcription levels. The TBP-promoter DNA complex contains sharply bent DNA and its interaction lifetime is limited by the ATP-dependent TBP displacement activity of the Snf2/Swi2 ATPase Mot1. Several mechanisms for Mot1 action have been proposed, but how it catalyzes TBP removal from DNA is unknown. To better understand the Mot1 mechanism, native gel electrophoresis and FRET were used to determine how Mot1 affects the trajectory of DNA in the TBP-DNA complex. Strikingly, in the absence of ATP, Mot1 acts to unbend DNA, whereas TBP remains closely associated with the DNA in a stable Mot1-TBP-DNA ternary complex. Interestingly, and in contrast to full-length Mot1, the isolated Mot1 ATPase domain binds DNA, and its affinity for DNA is nucleotide-dependent, suggesting parallels between the Mot1 mechanism and DNA translocation-based mechanisms of chromatin remodeling enzymes. Based on these findings, a model is presented for Mot1 that links a DNA conformational change with ATP-induced DNA translocation. PMID- 22298789 TI - Fine spatial assembly for construction of the phenol-binding pocket to capture bisphenol A in the human nuclear receptor estrogen-related receptor gamma. AB - Various lines of evidence have shown that bisphenol A (BPA) acts as an endocrine disruptor that affects various hormones even at merely physiological levels. We demonstrated recently that BPA binds strongly to human nuclear receptor estrogen related receptor gamma (ERRgamma), one of 48 nuclear receptors. Based on X-ray crystal analysis of the ERRgamma ligand-binding domain (LBD)/BPA complex, we demonstrated that ERRgamma receptor residues, Glu275 and Arg316, function as the intrinsic-binding site of the phenol-hydroxyl group of BPA. If these phenol hydroxyl<->Glu275 and Arg316 hydrogen bonds anchor the A-benzene ring of BPA, the benzene-phenyl group of BPA would be in a pocket constructed by specific amino acid side chain structures. In the present study, by evaluating the Ala-replaced mutant receptors, we identified such a ligand-binding pocket. Leu268, Leu271, Leu309 and Tyr326, in addition to the previously reported participants Glu275 and Arg316, were found to make a receptacle pocket for the A-ring, whereas Ile279, Ile310 and Val313 were found to assist or structurally support these residues. The results revealed that each amino acid residue is an essential structural element for the strong binding of BPA to ERRgamma. PMID- 22298790 TI - Sustained response to tocilizumab, anti-IL-6 antibody, following anti-TNF-alpha failure in a patient with relapsing polychondritis complicated by aortitis. PMID- 22298791 TI - What is meant by active disease in the NICE recommendation on use of combination therapy in early RA? PMID- 22298792 TI - Inflammatory lesions of the orbit: a single paediatric rheumatology centre experience. AB - OBJECTIVES: To describe the clinical, laboratory, histopathological presentations and final diagnoses for children presenting to a tertiary paediatric rheumatology service with an inflammatory lesion of the orbit. METHODS: This was a retrospective descriptive case series of children with an inflammatory lesion of the orbit presenting to a single paediatric rheumatology service between January 1999 and July 2010. RESULTS: Ten patients, median age 11.5 (range 3.1-16.2) years at referral to the paediatric rheumatology department were identified; median duration of symptoms at referral was 9 (0.75-17) months. Imaging was performed in 9/10 cases: orbital MRI (n = 4), orbital CT scan (n = 1), both MRI and CT scan (n = 4). All 10 patients had an orbital biopsy; 2 patients had repeat biopsies. The final diagnoses were granulomatosis with polyangiitis (Wegener's) (n = 5; ANCA positive n = 4, ANCA negative n = 1), idiopathic orbital inflammation (n = 3), atypical mycobacterial infection (n = 1) and sarcoidosis (n = 1). CONCLUSION: Inflammatory mass lesion of the orbit is an unusual presentation in children. The differential diagnosis is wide and may evolve over time. Orbital biopsy and screening for systemic features is essential before treatment with CSs or other immunosuppressants to exclude malignancy, infection, vascular lesions, autoimmune conditions or other causes of orbital inflammation that can be associated with serious systemic manifestations. PMID- 22298793 TI - Influenza A/H1N1 vaccination of patients with SLE: can antimalarial drugs restore diminished response under immunosuppressive therapy? AB - OBJECTIVE: To assess the efficacy and safety of pandemic 2009 influenza A (H1N1) in SLE under different therapeutic regimens. METHODS: A total of 555 SLE patients and 170 healthy controls were vaccinated with a single dose of a non-adjuvanted preparation. According to current therapy, patients were initially classified as SLE No Therapy (n = 75) and SLE with Therapy (n = 480). Subsequent evaluations included groups under monotherapy: chloroquine (CQ) (n = 105), prednisone (PRED) >=20 mg (n = 76), immunosuppressor (IS) (n = 95) and those with a combination of these drugs. Anti-H1N1 titres and seroconversion (SC) rate were evaluated at entry and 21 days post-vaccination. RESULTS: The SLE with Therapy group had lower SC compared with healthy controls (59.0 vs 80.0%; P < 0.0001), whereas the SLE No Therapy group had equivalent SC (72 vs 80.0%; P = 0.18) compared with healthy controls. Further comparison revealed that the SC of SLE No Therapy (72%) was similar to the CQ group (69.5%; P = 0.75), but it was significantly reduced in PRED >=20 mg (53.9%; P = 0.028), IS (55.7%; P = 0.035) and PRED >=20 mg + IS (45.4%; P = 0.038). The concomitant use of CQ in each of these later regimens was associated with SC responses comparable with SLE No Therapy group (72%): PRED >=20 mg + CQ (71.4%; P = 1.00), IS + CQ (65.2%; P = 0.54) and PRED >=20 mg + IS + CQ (57.4%; P = 0.09). CONCLUSION: Pandemic influenza A H1N1/2009 vaccine response is diminished in SLE under immunosuppressive therapy and antimalarials seems to restore this immunogenicity. Trial registration. www.clinicaltrials.gov, NCT01151644. PMID- 22298794 TI - Association of advanced chronic progressive nephropathy (CPN) with renal tubule tumors and precursor hyperplasia in control F344 rats from two-year carcinogenicity studies. AB - From the archives of the National Toxicology Program, National Institutes of Health, kidney sections from twenty-four carcinogenicity studies (representing twenty-three chemicals) in male and female F344 rats were histopathologically re evaluated to grade the severity of chronic progressive nephropathy (CPN) on an expanded scale of 0-8, and to record the presence of renal tubule tumors (RTT) and their precursor, atypical tubule hyperplasia (ATH). The data were statistically analyzed using SAS software for logistic regression analysis. This histopathological survey of 2,436 F344 rats showed clear evidence of a qualitative and statistically significant association between advanced stages of CPN severity and the development of low-grade RTT and ATH. Advanced CPN severity therefore represents a risk factor for the development of RTT and appears to be an underlying basis for spontaneous occurrence of RTT in the F344 rat. The difference in incidence and severity of CPN between the sexes also explains the 9:1 male-to-female sex difference in the spontaneous occurrence of ATH and RTT observed here. The regulatory significance of this finding is that chemicals exacerbating CPN as their only renal effect are likely to show a numerical increase in RTT with dose, which does not represent a direct tumorigenic effect of the chemical. PMID- 22298795 TI - Myocardial mononuclear cell infiltrates are not associated with increased serum cardiac troponin I in cynomolgus monkeys. AB - Myocardial mononuclear cell infiltrate is a spontaneous cardiac finding commonly identified in laboratory cynomolgus monkeys. The infiltrates are predominantly composed of macrophages with lesser lymphocytes and are not typically associated with histologically detectable cardiomyocyte degeneration. These infiltrates are of concern because they confound interpretation of test article-related histopathology findings in nonclinical safety toxicology studies. The interpretation of safety studies would be simplified by a biomarker that could identify myocardial infiltrates prior to animal placement on study. We hypothesized that monkeys with myocardial mononuclear cell infiltrates could be identified before necropsy using an ultrasensitive immunoassay for cardiac troponin I (cTnI). Serum cTnI concentrations in monkeys with myocardial infiltrates were not higher than those in monkeys without infiltrates at any of the sampling times before and on the day of necropsy. Increased serum cTnI levels are not suitable for screening monkeys with myocardial mononuclear cell infiltrates before placement in the study. PMID- 22298796 TI - Fixation temperature affects DNA integrity in the testis as measured by the TUNEL assay. AB - Mature rat testes and liver were fixed with Bouin's fluid (BF) or modified Davidson's fixative (mDF) at room temperature (23 degrees C) or 4 degrees C, and DNA integrity was examined by the TUNEL assay. When testes were fixed in BF, TUNEL-stained cells were more prevalent than when fixation occurred in mDF. Independent of fixative, TUNEL-staining was higher when testes were fixed at room temperature relative to 4 degrees C. Significant effects were present for fixative and temperature of fixation, but not their interaction. Relative to BF, mDF also provided for lower TUNEL-staining in liver, but staining was not affected by fixation temperature. Since the TUNEL assay depends on the detection of fragmented DNA strands, harsh fixatives that induce breaks in the DNA can introduce substantial artifacts. Such potential artifacts are especially prevalent in a tissue such as testes with its ongoing division and differentiation activities. Therefore, the current findings lead the authors to conclude that fixation of mature testes in mDF at 4 degrees C minimizes generation of false TUNEL-positive cells. PMID- 22298797 TI - Serial assessment of coronary artery response to paclitaxel-eluting stents using optical coherence tomography. AB - BACKGROUND: The paucity of longitudinal, serial high-resolution imaging studies has limited our understanding of in vivo arterial response to drug-eluting stents. We sought to investigate the human coronary response to paclitaxel eluting stent implantation, using serial optical coherence tomography assessments. METHODS AND RESULTS: Thirty patients with at least 2 significant coronary lesions in different vessels were treated with a paclitaxel-eluting stent. The most severe stenosis (lesion A) was treated at the initial procedure, and the second target vessel (lesion B) was stented 3 months later. Optical coherence tomography was performed at baseline, 3-, and 9-month follow-up for lesions A and baseline and 6 months for lesions B. Prespecified end points were percent of uncovered and malapposed struts over time. In lesions A, uncovered struts were 3.77+/-4.94% and 3.02+/-4.35% at 3 versus 9 months (P=NS). Malapposed struts were 3.55+/-5.16% at post-procedure, 1.51+/-3.52% at 3 months, and 0.60+/ 1.82% at 9 months (P<0.05, at 3 versus 9 months). Strut-level neointimal thickness was 0.19+/-0.09 mm and 0.20+/-0.11 mm (P=NS) over time. Newly acquired malapposition was detected in 10.4% and 3.3% of 2.5-mm segments at 3- and 9-month follow-up. In lesions B, uncovered struts were 2.91+/-5.47% at 6-months. Malapposed struts were 4.94+/-6.70% post-procedure and 1.01+/-3.11% at 6 months (P<0.01), with 0.19+/-0.09-mm neointimal thickness at follow-up. CONCLUSIONS: Optical coherence tomography imaging suggested the first 3 months to be the period with most biological activity after paclitaxel-eluting stent implantation, when the proliferative reaction mainly occurs and malapposition resolves. A less active, yet continuous, dynamic arterial response, with resolution and development of malapposition, occurs through 9 months post-treatment. PMID- 22298798 TI - No association of ABCB1 C3435T genotype with clopidogrel response or risk of stent thrombosis in patients undergoing coronary stenting. AB - BACKGROUND: The prodrug clopidogrel requires intestinal absorption by the efflux pump P-glycoprotein MDR1 (multidrug resistant-1), encoded by the ABCB1 gene. Prior studies suggested that a common and functional genetic variant (C3435T, rs1045642) within ABCB1 influences clopidogrel treatment efficacy; however, existing data are highly inconsistent, because other studies failed to replicate this postulated association. Thus, the aim of this study was to assess the association of ABCB1 C3435T genotypes with the antiplatelet efficacy of clopidogrel and the risk of stent thrombosis (ST) in large cohorts of clopidogrel treated patients undergoing percutaneous coronary intervention. METHODS AND RESULTS: DNA samples from 1524 clopidogrel-treated patients undergoing percutaneous coronary intervention were genotyped for ABCB1 C3435T, and ADP induced platelet aggregation was assessed in whole blood on a Multiplate analyzer. The clinical impact of the genetic variant was investigated by comparison of genotype frequencies in a registry of 66 cases with definite drug eluting stent ST versus an ST-free control cohort (n=1408). Platelet aggregation values were similar across ABCB1 C3435T genotypes (P=0.73). No significant influence of ABCB1 C3435T genotypes on the occurrence of ST was found when ST case subjects were compared with control subjects (P=0.89). CONCLUSIONS: ABCB1 C3435T genotypes did not influence the antiplatelet response to clopidogrel or the risk of ST in clopidogrel-treated patients undergoing percutaneous coronary intervention. Routine genotyping of ABCB1 C3435T polymorphisms should not be recommended for risk stratification in clopidogrel-treated patients undergoing percutaneous coronary intervention who are similar to those evaluated in the present study. PMID- 22298799 TI - Predictors of periprocedural (type IVa) myocardial infarction, as assessed by frequency-domain optical coherence tomography. AB - BACKGROUND: Frequency-domain optical coherence tomography (FD-OCT) is easily able to define both pre- and post-stenting features of the atherosclerotic plaque that can potentially be related to periprocedural complications. We sought to examine which FD-OCT-defined characteristics, assessed both before and after stent deployment, predicted periprocedural (type IVa) myocardial infarction (MI). METHODS AND RESULTS: FD-OCT was performed before and after coronary stenting in 50 patients undergoing percutaneous coronary intervention (PCI) for either non-ST segment elevation MI (NSTEMI) or stable angina. All patients underwent single vessel stenting, and only drug-eluting stents were implanted. Troponin T was analyzed on admission, before PCI, and at 12 and 24 hours after PCI, and type IVa MI was defined in stable angina as a rise of at least 3* upper reference limit and in NSTEMI as a pre-PCI troponin T fall, followed by post-PCI troponin T rise >20%. Type IVa MI was diagnosed in 21 patients, while the remaining 29 represented the control group. FD-OCT analysis showed that thin-cap fibroatheroma (76.2% versus 41.4%; P=0.017) prior to PCI, intrastent thrombus (61.9% versus 20.7%; P=0.04), and intrastent dissection (61.9% versus 31%; P=0.03) after PCI were significantly more frequent in type IVa MI than in the control group. Multivariate logistic regression analysis confirmed thin-cap fibroatheroma (OR 29.7, 95% CI 1.4 to 32.1), intrastent thrombus (OR 5.5, CI 1.2 to 24.9) and intrastent dissection (OR 5.3, CI 1.2 to 24.3) as independent predictors of type IVa MI. CONCLUSIONS: In conclusion, presence of thin-cap fibroatheroma at pre-PCI FD-OCT and of intrastent thrombus and intrastent dissection at post-PCI FD-OCT predict type IVa MI in a contemporary sample of patients treated with second generation drug-eluting stents. Interestingly, 2 of the 3 predictors of type IVa MI were not apparent at pre-PCI FD-OCT. PMID- 22298800 TI - Coronary microcirculatory resistance is independent of epicardial stenosis. AB - BACKGROUND: Recent studies show that coronary microcirculatory impairment is an independent predictor of poor outcomes in patients with cardiovascular disease. However, controversy exists over whether microcirculatory resistance, a measure of coronary microcirculatory status, is dependent on epicardial stenosis severity. Previous studies demonstrating that microcirculatory resistance is dependent on epicardial stenosis severity have not accounted for collateral flow in their measurement of microcirculatory resistance. We investigated whether the index of microcirculatory resistance is independent of epicardial stenosis by comparing the index of microcirculatory resistance (IMR) levels in patients before and after percutaneous coronary intervention (PCI). METHODS AND RESULTS: Consecutive patients undergoing elective PCI of the left anterior descending artery were recruited. Patients who developed periprocedural myocardial infarction were excluded. A pressure-temperature sensor wire was used to measure the apparent IMR (IMR(app)), which does not adjust for collateral flow, and the true IMR (IMR(true)), which incorporates wedge pressure measurement to account for collateral flow, before and after PCI. In 43 patients, there was no difference between pre- and post-PCI IMR(true) (mean difference=0.8+/-11.7, P=0.675). IMR(app) was higher pre-PCI compared with post-PCI (mean difference=10.0+/-14.5, P<0.001). IMR(app) was higher than IMR(true) (mean difference=9.3+/-14.2, P<0.001), and the difference between the IMR(app) and IMR(true) became greater with decreasing fractional flow reserve and increasing coronary wedge pressure. Pre-PCI fractional flow reserve correlated modestly with IMR(app) (r=-0.33, P=0.03), but not IMR(true) (r=0.26, P=0.10). CONCLUSIONS: Coronary microcirculatory resistance is independent of functional epicardial stenosis severity when collateral flow is taken into account. PMID- 22298801 TI - Chemotherapy and fingerprint loss: beyond cosmetic. AB - Hand-foot syndrome (HFS) is a common adverse reaction to several chemotherapy drugs. Focus has been on the clinically relevant sequelae associated with this condition, with fingerprint loss receiving little attention. We report the case of a 53-year old male patient with terminal metastatic adenocarcinoma of the rectum involving the liver and lungs who developed grade 3 HFS while on capecitabine therapy. This resulted in his inability to process required government papers as a result of the loss of his fingerprints, imposing significant inconvenience and frustration on a person severely challenged by his deteriorating health. We believe clinicians should pay more attention to this possible outcome that can add additional stress in the lives of patients whose quality of life is already severely compromised. PMID- 22298802 TI - Short-term effects on bone turnover markers of a single high dose of oral vitamin D3. AB - CONTEXT: Vitamin D deficiency is often treated or prevented by high intermittent doses of vitamin D to achieve a better treatment adherence, but treatment outcomes were contradictory, and even a transient increase in fracture and fall risk was reported. OBJECTIVE: The objective of the study was to investigate the short-term effects on bone turnover markers of a single bolus of vitamin D3. DESIGN, SETTING, PATIENTS, AND INTERVENTION: Twelve elderly subjects (eight women, four men; mean age 76 +/- 3 yr) were given a single oral bolus of 600,000 IU vitamin D3. Blood samples were taken at baseline and 1, 3, 7, 14, 30, 60, and 90 d after vitamin D3 administration. Twenty-four subjects served as controls. MAIN OUTCOME MEASURES: Changes in serum levels of 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D, PTH, C-terminal-telopeptides of type I collagen, cross linked N-telopeptide of type I collagen (sNTX), osteocalcin, and bone-specific alkaline phosphatase. RESULTS: No relevant changes in 25OHD and bone turnover markers were observed in the controls. In treated subjects, serum 25OHD attained a peak increment to 67.1 +/- 17.1 ng/ml (P < 0.001) at d 3. Subsequently it slowly decreased to 35.2 +/- 5.8 ng/ml (P <0.01 vs. a baseline value of 21.7 +/- 5.6 ng/ml). Mean serum PTH concentration decreased by 25-50% and serum 1,25 dihydroxyvitamin D rose by 25-50%. Serum CTX and sNTX rose significantly at d 1 (P < 0.01), they attained a peak increment greater than 50% at d 3, and they subsequently decreased almost back to baseline values at d 90. Serum osteocalcin slightly rose within the first 3 d and then declined by d 60. No changes were observed in serum bone-specific alkaline phosphatase. CONCLUSIONS: Our results indicate that the use of large doses of vitamin D may be associated with acute increases in C-terminal-telopeptides of type I collagen and sNTX, which may explain the negative clinical results obtained by using intermittent high doses of vitamin D to treat or prevent vitamin D deficiency. PMID- 22298803 TI - Population-based trends in osteoporosis management after new initiations of long term systemic glucocorticoids (1998-2008). AB - OBJECTIVES: Our objective was to describe changes in glucocorticoid-induced osteoporosis (GIOP) preventive care from 1998-2008 including rates and correlates of bone mineral density (BMD) testing and osteoporosis treatment in new long-term glucocorticoid initiations. METHODS: A population-based study of adults aged 20 yr or older in Manitoba, Canada, was conducted using linked healthcare databases. Subjects with new long-term (>=90 d) systemic glucocorticoid initiations were identified within each fiscal year. High-quality GIOP preventive care was defined by the composite of BMD testing or osteoporosis treatment within 6 months of starting glucocorticoids. For each initiation, we identified sociodemographic and clinical characteristics, prednisone dose equivalents, and prescriber specialty. Multivariable Poisson regression models were used to calculate adjusted incidence rate ratios (aIRR). RESULTS: We studied 17,736 new long-term glucocorticoid initiations; one third were at least 10 mg prednisone daily, and most (64%) were prescribed by general practitioners. Overall, 6-month rates of BMD testing were 6%, osteoporosis treatment 22%, and the composite of testing or treatment 25%. From 1998-2008, there were modest increases in BMD testing (from 4 to 6%), osteoporosis treatment (from 15 to 24%), and testing or treatment [from 17 to 27%; aIRR = 1.51; 95% confidence interval (CI) = 1.40-1.63]. High-quality GIOP preventive care varied significantly by age (16% for those <50 yr vs. 27% for those >=70 yr; aIRR = 0.57; 95% CI = 0.52-0.63), sex (13% for men vs. 34% for women; aIRR = 0.40; 95% CI = 0.37-0.43), and prescriber (23% general practice vs. 44% rheumatology; aIRR = 0.56; 95% CI = 0.52-0.60). CONCLUSIONS: Quality of GIOP preventive care has improved but remains suboptimal with only one quarter of those starting long-term glucocorticoids receiving BMD testing or osteoporosis treatment. Interventions to improve GIOP prevention, especially targeting younger patients, men, and nonspecialists, are needed. PMID- 22298804 TI - Fat content in liver and skeletal muscle changes in a reciprocal manner in patients with acromegaly during combination therapy with a somatostatin analog and a GH receptor antagonist: a randomized clinical trial. AB - CONTEXT: Pegvisomant is a GH antagonist, which is used for the treatment of acromegalic patients. It effectively blocks the hepatic and peripheral effects of GH, but transient elevations in circulating liver enzymes of unknown pathogenesis may occur, which seems to be more prevalent when the treatment is combined with a somatostatin analog (SA). Accumulation of intrahepatic lipid is a known cause of elevated liver enzymes, and there is evidence to suggest that GH impacts lipid content in liver and skeletal muscle. OBJECTIVE: Our objective was to measure lipid content in liver and skeletal muscle in acromegalic patients before and after cotreatment with pegvisomant and SA as compared with SA monotherapy. DESIGN: Eighteen acromegalic patients well controlled on SA monotherapy were randomized in a parallel study over 24 wk to 1) unchanged SA monotherapy, or 2) cotreatment with pegvisomant (15-30 mg twice a week) and SA (half the usual dosage). SETTING: This was an investigator-initiated study in a single tertiary referral center. MAIN OUTCOME MEASURES: Intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) was assessed by 1H magnetic resonance spectroscopy. RESULTS: IHL increased in the cotreatment group compared with SA only (P = 0.002). The increase was positively correlated to weekly pegvisomant dose (r2 = 0.52; P = 0.01). By contrast, IMCL decreased in the cotreatment group compared with SA only (P = 0.01). These changes related neither to insulin sensitivity nor inflammatory markers. CONCLUSION: Cotreatment with pegvisomant and a reduced SA dose increase IHL and decrease IMCL compared with SA monotherapy. The clinical implications remain unclear, but increased IHL may be causally linked to the transient elevations in liver enzymes observed during pegvisomant treatment. PMID- 22298805 TI - Remote copulation: male adaptation to female cannibalism. AB - Sexual cannibalism by females and associated male behaviours may be driven by sexual conflict. One such male behaviour is the eunuch phenomenon in spiders, caused by total genital emasculation, which is a seemingly maladaptive behaviour. Here, we provide the first empirical testing of an adaptive hypothesis to explain this behaviour, the remote copulation, in a highly sexually cannibalistic orb-web spider Nephilengys malabarensis. We demonstrate that sperm transfer continues from the severed male organ into female genitals after the male has been detached from copula. Remote copulation increases the total amount of sperm transferred, and thus probably enhances paternity. We conclude that the mechanism may have evolved in response to sexual cannibalism and female-controlled short copulation duration. PMID- 22298806 TI - Novel use of burrow casting as a research tool in deep-sea ecology. AB - Although the deep sea is the largest ecosystem on Earth, its infaunal ecology remains poorly understood because of the logistical challenges. Here we report the morphology of relatively large burrows obtained by in situ burrow casting at a hydrocarbon-seep site and a non-seep site at water depths of 1173 and 1455 m, respectively. Deep and complex burrows are abundant at both sites, indicating that the burrows introduce oxygen-rich sea water into the deep reducing substrate, thereby influencing benthic metabolism and nutrient fluxes, and providing an oxic microhabitat for small organisms. Burrow castings reveal that the solemyid bivalve Acharax johnsoni mines sulphide from the sediment, as documented for related shallow-water species. To our knowledge, this is the first study to examine in situ burrow morphology in the deep sea by means of burrow casting, providing detailed information on burrow structure which will aid the interpretation of seabed processes in the deep sea. PMID- 22298807 TI - The ten most read articles published in Circulation Research in 2011. PMID- 22298808 TI - Viral gene transfer rescues arrhythmogenic phenotype and ultrastructural abnormalities in adult calsequestrin-null mice with inherited arrhythmias. AB - RATIONALE: Catecholaminergic polymorphic ventricular tachycardia is an inherited disease that predisposes to cardiac arrest and sudden death. The disease is associated with mutations in the genes encoding for the cardiac ryanodine receptor (RyR2) and cardiac calsequestrin (CASQ2). CASQ2 mutations lead to a major loss of CASQ2 monomers, possibly because of enhanced degradation of the mutant protein. The decrease of CASQ2 is associated with a reduction in the levels of Triadin (TrD) and Junctin (JnC), two proteins that form, with CASQ2 and RyR2, a macromolecular complex devoted to control of calcium release from the sarcoplasmic reticulum. OBJECTIVE: We intended to evaluate whether viral gene transfer of wild-type CASQ2 may rescue the broad spectrum of abnormalities caused by mutant CASQ2. METHODS AND RESULTS: We used an adeno-associated serotype 9 viral vector to express a green fluorescent protein-tagged CASQ2 construct. Twenty weeks after intraperitoneal injection of the vector in neonate CASQ2 KO mice, we observed normalization of the levels of calsequestrin, triadin, and junctin, rescue of electrophysiological and ultrastructural abnormalities caused by CASQ2 ablation, and lack of life-threatening arrhythmias. CONCLUSIONS: We have proven the concept that induction of CASQ2 expression in knockout mice reverts the molecular, structural, and electric abnormalities and prevents life threatening arrhythmias in CASQ2-defective catecholaminergic polymorphic ventricular tachycardia mice. These data support the view that development of CASQ2 viral gene transfer could have clinical application. PMID- 22298809 TI - Ethanol exposure induces upregulation of specific microRNAs in zebrafish embryos. AB - Prenatal exposure to ethanol leads to a myriad of developmental disorders known as fetal alcohol spectrum disorder, often characterized by growth and mental retardation, central nervous system damage, and specific craniofacial dysmorphic features. The mechanisms of ethanol toxicity are not fully understood, but exposure during development affects the expression of several genes involved in cell cycle control, apoptosis, and transcriptional regulation. MicroRNAs (miRNAs) are implicated in some of these processes, however, it is not yet clear if they are involved in ethanol-induced toxicity. In order to clarify this question, we have exposed zebrafish embryos to ethanol and evaluated whether a miRNA deregulation signature could be obtained. Zebrafish embryos were exposed to 1 and 1.5% of ethanol from 4 h postfertilization (hpf) to 24 hpf. The miRNA expression profiles obtained reveal significant miRNA deregulation and show that both ethanol concentrations upregulate miR-153a, miR-725, miR-30d, let-7k, miR-100, miR-738, and miR-732. Putative gene targets of deregulated miRNAs are involved in cell cycle control, apoptosis, and transcription, which are the main processes affected by ethanol toxicity. The conservation of affected mechanisms among vertebrates leads us to postulate that similar miRNA deregulation occurs in humans, highlighting a relevant role of miRNAs in ethanol toxicology. PMID- 22298810 TI - Cross-species comparisons of transcriptomic alterations in human and rat primary hepatocytes exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. AB - A toxicogenomics approach was used to qualitatively and quantitatively compare the gene expression changes in human and rat primary hepatocytes exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Hepatocytes from five individual rats and five individual humans were exposed for 24 h to 11 concentrations of TCDD ranging from 0.00001 to 100nM and a vehicle control. Gene expression changes were analyzed using whole-genome microarrays containing 13,002 orthologs. Significant changes in expression of individual orthologs at any concentration (fold change [FC] +/- 1.5 and false discovery rate < 0.05) were higher in the rat (1547) compared with human hepatocytes (475). Only 158 differentially expressed orthologs were common between rats and humans. Enrichment analysis was performed on the differentially expressed orthologs in each species with 49 and 34 enriched human and rat pathways, respectively. Only 12 enriched pathways were shared between the two species. The results demonstrate significant cross-species differences in expression at both the gene and pathway level. Benchmark dose analysis of gene expression changes showed an average 18-fold cross-species difference in potency among differentially expressed orthologs with the rat more sensitive than the human. Similar cross-species differences in potency were observed for signaling pathways. Using the maximum FC in gene expression as a measure of efficacy, the human hepatocytes showed on average a 20% lower efficacy among the individual orthologs showing differential expression. The results provide evidence for divergent cross-species gene expression changes in response to TCDD and are consistent with epidemiological and clinical evidence showing humans to be less sensitive to TCDD-induced hepatotoxicity. PMID- 22298813 TI - Haemocompatibility and ion exchange capability of nanocellulose polypyrrole membranes intended for blood purification. AB - Composites of nanocellulose and the conductive polymer polypyrrole (PPy) are presented as candidates for a new generation of haemodialysis membranes. The composites may combine active ion exchange with passive ultrafiltration, and the large surface area (about 80 m(2) g(-1)) could potentially provide compact dialysers. Herein, the haemocompatibility of the novel membranes and the feasibility of effectively removing small uraemic toxins by potential-controlled ion exchange were studied. The thrombogenic properties of the composites were improved by applying a stable heparin coating. In terms of platelet adhesion and thrombin generation, the composites were comparable with haemocompatible polymer polysulphone, and regarding complement activation, the composites were more biocompatible than commercially available membranes. It was possible to extract phosphate and oxalate ions from solutions with physiological pH and the same tonicity as that of the blood. The exchange capacity of the materials was found to be 600 +/- 26 and 706 +/- 31 MUmol g(-1) in a 0.1 M solution (pH 7.4) and in an isotonic solution of phosphate, respectively. The corresponding values with oxalate were 523 +/- 5 in a 0.1 M solution (pH 7.4) and 610 +/- 1 MUmol g(-1) in an isotonic solution. The heparinized PPy-cellulose composite is consequently a promising haemodialysis material, with respect to both potential-controlled extraction of small uraemic toxins and haemocompatibility. PMID- 22298814 TI - Implications of functional similarity for gene regulatory interactions. AB - If one gene regulates another, those two genes are likely to be involved in many of the same biological functions. Conversely, shared biological function may be suggestive of the existence and nature of a regulatory interaction. With this in mind, we develop a measure of functional similarity between genes based on annotations made to the Gene Ontology in which the magnitude of their functional relationship is also indicative of a regulatory relationship. In contrast to other measures that have previously been used to quantify the functional similarity between genes, our measure scales the strength of any shared functional annotation by the frequency of that function's appearance across the entire set of annotations. We apply our method to both Escherichia coli and Saccharomyces cerevisiae gene annotations and find that the strength of our scaled similarity measure is more predictive of known regulatory interactions than previously published measures of functional similarity. In addition, we observe that the strength of the scaled similarity measure is correlated with the structural importance of links in the known regulatory network. By contrast, other measures of functional similarity are not indicative of any structural importance in the regulatory network. We therefore conclude that adequately adjusting for the frequency of shared biological functions is important in the construction of a functional similarity measure aimed at elucidating the existence and nature of regulatory interactions. We also compare the performance of the scaled similarity with a high-throughput method for determining regulatory interactions from gene expression data and observe that the ontology-based approach identifies a different subset of regulatory interactions compared with the gene expression approach. We show that combining predictions from the scaled similarity with those from the reconstruction algorithm leads to a significant improvement in the accuracy of the reconstructed network. PMID- 22298815 TI - Hydrodynamics of the double-wave structure of insect spermatozoa flagella. AB - In addition to conventional planar and helical flagellar waves, insect sperm flagella have also been observed to display a double-wave structure characterized by the presence of two superimposed helical waves. In this paper, we present a hydrodynamic investigation of the locomotion of insect spermatozoa exhibiting the double-wave structure, idealized here as superhelical waves. Resolving the hydrodynamic interactions with a non-local slender body theory, we predict the swimming kinematics of these superhelical swimmers based on experimentally collected geometric and kinematic data. Our consideration provides insight into the relative contributions of the major and minor helical waves to swimming; namely, propulsion is owing primarily to the minor wave, with negligible contribution from the major wave. We also explore the dependence of the propulsion speed on geometric and kinematic parameters, revealing counterintuitive results, particularly for the case when the minor and major helical structures are of opposite chirality. PMID- 22298816 TI - Characterization of the phosphatic mineral of the barnacle Ibla cumingi at atomic level by solid-state nuclear magnetic resonance: comparison with other phosphatic biominerals. AB - Ibliform barnacles are among the few invertebrate animals harnessing calcium phosphate to construct hard tissue. The (31)P solid-state NMR (SSNMR) signal from the shell plates of Ibla cumingi (Iblidae) is broader than that of bone, and shifted by ca 1 ppm to low frequency. (1)H-(31)P heteronuclear correlation (HETCOR) experiments show a continuum of different phosphorus/phosphate atomic environments, close to hydrogen populations with resonance frequencies between ca 10 and 20 ppm. Associated (1)H and (31)P chemical shifts argue the coexistence of weakly (high (31)P frequency, low (1)H frequency) to more strongly (lower (31)P frequency, higher (1)H frequency) hydrogen-bonded hydrogen phosphate-like molecular/ionic species. There is no resolved signal from discrete OH(-) ions. (13)C SSNMR shows chitin, protein and other organic biomolecules but, unlike bone, there are no significant atomic scale organic matrix-mineral contacts. The poorly ordered hydrogen phosphate-like iblid mineral is strikingly different, structurally and compositionally, from both vertebrate bone mineral and the more crystalline fluoroapatite of the linguliform brachiopods. It probably represents a previously poorly characterized calcium phosphate biomineral, the evolution of which may have reflected either the chemical conditions of ancestral seas or the mechanical advantages of phosphatic biomineralization over a calcium carbonate equivalent. PMID- 22298817 TI - Resonance in herbaceous plant stems as a factor in vibrational communication of pentatomid bugs (Heteroptera: Pentatomidae). AB - Pentatomid bugs communicate using substrate-borne vibrational signals that are transmitted along herbaceous plant stems in the form of bending waves with a regular pattern of minimal and maximal amplitude values with distance. We tested the prediction that amplitude variation is caused by resonance, by measuring amplitude profiles of different vibrational pulses transmitted along the stem of a Cyperus alternifolius plant, and comparing their patterns with calculated spatial profiles of corresponding eigenfrequencies of a model system. The measured distance between nodes of the amplitude pattern for pulses with different frequencies matches the calculated values, confirming the prediction that resonance is indeed the cause of amplitude variation in the studied system. This confirmation is supported by the resonance profile obtained by a frequency sweep, which matches theoretical predictions of the eigenfrequencies of the studied system. Signal bandwidth influences the amount of amplitude variation. The effect of both parameters on signal propagation is discussed in the context of insect vibrational communication. PMID- 22298818 TI - A fly's view of the hematopoietic niche. PMID- 22298819 TI - Using the hemoglobin switch for the treatment of sickle cell disease. PMID- 22298820 TI - Allosteric BCR-ABL inhibitors in Philadelphia chromosome-positive acute lymphoblastic leukemia: novel opportunities for drug combinations to overcome resistance. PMID- 22298821 TI - HOXC4 homeoprotein efficiently expands human hematopoietic stem cells and triggers similar molecular alterations as HOXB4. AB - BACKGROUND: Expansion of hematopoietic stem cells represents an important objective for improving cell and gene therapy protocols. Retroviral transduction of the HoxB4 homeogene in mouse and human hematopoietic stem cells and hematopoietic progenitors is known to promote the cells' expansion. A safer approach consists in transferring homeobox proteins into hematopoietic stem cells taking advantage of the natural ability of homeoproteins to cross cell membranes. Thus, HOXB4 protein transfer is operative for expanding human hematopoietic cells, but such expansion needs to be improved. DESIGN AND METHODS: To that aim, we evaluated the effects of HOXC4, a protein encoded by a HOXB4 paralog gene, by co-culturing HOXC4-producing stromal cells with human CD34(+) hematopoietic cells. Numbers of progenitors and stem cells were assessed by in vitro cloning assays and injection into immuno-deficient mice, respectively. We also looked for activation or inhibition of target downstream gene expression. RESULTS: We show that the HOXC4 homeoprotein expands human hematopoietic immature cells by 3 to 6 times ex vivo and significantly improves the level of in vivo engraftment. Comparative transcriptome analysis of CD34(+) cells subjected or not to HOXB4 or HOXC4 demonstrated that both homeoproteins regulate the same set of genes, some of which encode key hematopoietic factors and signaling molecules. Certain molecules identified herein are factors reported to be involved in stem cell fate or expansion in other models, such as MEF2C, EZH2, DBF4, DHX9, YPEL5 and Pumilio. CONCLUSIONS: The present study may help to identify new HOX downstream key factors potentially involved in hematopoietic stem cell expansion or in leukemogenesis. PMID- 22298822 TI - MDS-specific comorbidity index is useful to identify myelodysplastic patients who can have better outcome with 5-azacitidine. PMID- 22298823 TI - Classification of diffuse large B-cell lymphoma by immunohistochemistry demonstrates that elderly patients are more common in the non-GC subgroup and younger patients in the GC subgroup. PMID- 22298825 TI - Time-frequency analysis of short-lasting modulation of EEG induced by intracortical and transcallosal paired TMS over motor areas. AB - Dynamic changes in spontaneous electroencephalogram (EEG) rhythms can be seen to occur with a high rate of variability. An innovative method to study brain function is by triggering oscillatory brain activity with transcranial magnetic stimulation (TMS). EEG-TMS coregistration was performed on five healthy subjects during a 1-day experimental session that involved four steps: baseline acquisition, unconditioned single-pulse TMS, intracortical inhibition (ICI, 3 ms) paired-pulse TMS, and transcallosal stimulation over left and right primary motor cortex (M1). A time-frequency analysis based on the wavelet method was used to characterize rapid modifications of oscillatory EEG rhythms induced by TMS. Single, paired, and transcallosal TMS applied on the sensorimotor areas induced rapid desynchronization over the frontal and central-parietal electrodes mainly in the alpha and beta bands, followed by a rebound of synchronization, and rapid synchronization of delta and theta activity. Wavelet analysis after a perturbation approach is a novel way to investigate modulation of oscillatory brain activity. The main findings are consistent with the concept that the human motor system may be based on networklike oscillatory cortical activity and might be modulated by single, paired, and transcallosal magnetic pulses applied to M1, suggesting a phenomenon of fast brain activity resetting and triggering of slow activity. PMID- 22298826 TI - Functional connectivity of the frontal eye fields in humans and macaque monkeys investigated with resting-state fMRI. AB - Although the frontal eye field (FEF) has been identified in macaque monkeys and humans, practical constraints related to invasiveness and task demands have limited a direct cross-species comparison of its functional connectivity. In this study, we used resting-state functional MRI data collected from both awake humans and anesthetized macaque monkeys to examine and compare the functional connectivity of the FEF. A seed region analysis revealed consistent ipsilateral functional connections of the FEF with fronto-parietal cortical areas across both species. These included the intraparietal sulcus, dorsolateral prefrontal cortex, anterior cingulate cortex, and supplementary eye fields. The analysis also revealed greater lateralization of connectivity with the FEF in both hemispheres in humans than in monkeys. Cortical surface-based transformation of connectivity maps between species further corroborated the remarkably similar organization of the FEF functional connectivity. The results support an evolutionarily preserved fronto-parietal system and provide a bridge for linking data from monkey and human studies. PMID- 22298827 TI - Stability of gait and interlimb coordination in older adults. AB - Most falls in older adults occur when walking, specifically following a trip. This study investigated the short- and longer term responses of young (n = 24, 27.6 +/- 4.5 yr) and older adults (n = 18, 69.1 +/- 4.2 yr) to a trip during gait at comfortable speed and the role of interlimb coordination in recovery from tripping. Subjects walked on a self-paced treadmill when forward movement of their dominant leg was unexpectedly arrested for 250 ms. Recovery of center of mass (COM) movements and of double-support duration following perturbation was determined. In addition, the disruption and recovery of interlimb coordination of the arms and legs was evaluated. Although young and older subjects used similar lower limb strategies in response to the trip, older adults had less stable COM movement patterns before perturbation, had longer transient destabilization (>25%) after perturbation, required more gait cycles to recover double-support duration (older, 3.48 +/- 0.7 cycles; young, 2.88 +/- 0.4 cycles), and had larger phase shifts that persisted after perturbation (older, -83 degrees to -90 degrees ; young, -39 degrees to -42 degrees ). Older adults also had larger disruptions to interlimb coordination of the arms and legs. The timing of the initial disruption in coordination was correlated with the disturbance in gait stability only in young adults. In older adults, greater initial COM instability was related to greater longer term arm incoordination. These results suggest a relationship between interlimb coordination and gait stability, which may be associated with fall risk in older adults. Reduced coordination and gait stability suggest a need for stability-related functional training even in high functioning older adults. PMID- 22298828 TI - Adaptation of the preferred human bouncing pattern toward the metabolically optimal frequency. AB - Humans often appear to prefer movement patterns that minimize the metabolic energy expenditure of performing a task. However, it is not clear whether this preference is dependent on adaptation to feedback or results from a previously learned motor plan. We recently found that for a bouncing task with an identifiable neuromechanical resonant frequency, humans do not initially prefer to bounce at the resonant frequency despite its presumed metabolic benefits. The purpose of the present study was to determine whether humans adapt their preferred bouncing frequency over time to approach the metabolic optimum. Subjects (n = 12) performed a series of 6-min reclined bouncing trials while we quantified bounce frequency, metabolic rate, and rate of positive mechanical work performed on the body. In one trial, subjects bounced at their preferred frequency. In five other trials, subjects bounced at frequencies prescribed by a metronome to match specific percentages of their resonant frequency (80-120%). Positive mechanical work rate was held constant across trials by having subjects match real-time visual feedback to a target. The metabolic rate was lowest during prescribed frequency trials near resonance, not during the preferred frequency trial when subjects were free to choose the bouncing frequency. While the initial preferred frequency was lower than the resonant frequency, the preferred frequency gradually approached resonance over the course of 6 min. These results provide evidence that humans do not choose their preferred movement pattern based on an unchanging learned motor plan, but instead adapt their preferred frequency in response to feedback. Our findings may have implications for clinical populations, as reduced sensory acuity could prevent identification of the metabolically optimal movement pattern. PMID- 22298829 TI - Fast visual prediction and slow optimization of preferred walking speed. AB - People prefer walking speeds that minimize energetic cost. This may be accomplished by directly sensing metabolic rate and adapting gait to minimize it, but only slowly due to the compounded effects of sensing delays and iterative convergence. Visual and other sensory information is available more rapidly and could help predict which gait changes reduce energetic cost, but only approximately because it relies on prior experience and an indirect means to achieve economy. We used virtual reality to manipulate visually presented speed while 10 healthy subjects freely walked on a self-paced treadmill to test whether the nervous system beneficially combines these two mechanisms. Rather than manipulating the speed of visual flow directly, we coupled it to the walking speed selected by the subject and then manipulated the ratio between these two speeds. We then quantified the dynamics of walking speed adjustments in response to perturbations of the visual speed. For step changes in visual speed, subjects responded with rapid speed adjustments (lasting <2 s) and in a direction opposite to the perturbation and consistent with returning the visually presented speed toward their preferred walking speed, when visual speed was suddenly twice (one half) the walking speed, subjects decreased (increased) their speed. Subjects did not maintain the new speed but instead gradually returned toward the speed preferred before the perturbation (lasting >300 s). The timing and direction of these responses strongly indicate that a rapid predictive process informed by visual feedback helps select preferred speed, perhaps to complement a slower optimization process that seeks to minimize energetic cost. PMID- 22298830 TI - Sensitivity to temporal modulation rate and spectral bandwidth in the human auditory system: fMRI evidence. AB - Hierarchical models of auditory processing often posit that optimal stimuli, i.e., those eliciting a maximal neural response, will increase in bandwidth and decrease in modulation rate as one ascends the auditory neuraxis. Here, we tested how bandwidth and modulation rate interact at several loci along the human central auditory pathway using functional MRI in a cardiac-gated, sparse acquisition design. Participants listened passively to both narrowband (NB) and broadband (BB) carriers (1/4- or 4-octave pink noise), which were jittered about a mean sinusoidal amplitude modulation rate of 0, 3, 29, or 57 Hz. The jittering was introduced to minimize stimulus-specific adaptation. The results revealed a clear difference between spectral bandwidth and temporal modulation rate: sensitivity to bandwidth (BB > NB) decreased from subcortical structures to nonprimary auditory cortex, whereas sensitivity to slow modulation rates was largest in nonprimary auditory cortex and largely absent in subcortical structures. Furthermore, there was no parametric interaction between bandwidth and modulation rate. These results challenge simple hierarchical models, in that BB stimuli evoked stronger responses in primary auditory cortex (and subcortical structures) rather than nonprimary cortex. Furthermore, the strong preference for slow modulation rates in nonprimary cortex demonstrates the compelling global sensitivity of auditory cortex to modulation rates that are dominant in the principal signals that we process, e.g., speech. PMID- 22298831 TI - The representations of reach endpoints in posterior parietal cortex depend on which hand does the reaching. AB - Neurons in the parietal reach region (PRR) have been implicated in the sensory-to motor transformation required for reaching toward visually defined targets. The neurons in each cortical hemisphere might be specifically involved in planning movements of just one limb, or the PRR might code reach endpoints generically, independent of which limb will actually move. Previous work has shown that the preferred directions of PRR neurons are similar for right and left limb movements but that the amplitude of modulation may vary greatly. We now test the hypothesis that frames of reference and eye and hand gain field modulations will, like preferred directions, be independent of which hand moves. This was not the case. Many neurons show clear differences in both the frame of reference as well as in direction and strength of gain field modulations, depending on which hand is used to reach. The results suggest that the information that is conveyed from the PRR to areas closer to the motor output (the readout from the PRR) is different for each limb and that individual PRR neurons contribute either to controlling the contralateral-limb or else bimanual-limb control. PMID- 22298832 TI - The contribution of vision, proprioception, and efference copy in storing a neural representation for guiding trail leg trajectory over an obstacle. AB - Stepping over obstacles requires vision to guide the leading leg, but direct visual information is not available to guide the trailing leg. The neural mechanisms for establishing a stored obstacle representation and thus facilitating the trail leg trajectory in humans are unknown. Twenty-four subjects participated in one of three experiments, which were designed to investigate the contribution of visual, proprioceptive, and efference copy signals. Subjects stepped over an obstacle with their lead leg, stopped, and straddled the obstacle for a delay period before stepping over it with their trail leg while toe elevation was recorded. Subsequently, we calculated maximum toe elevation and toe clearance. First, we found that subjects could accurately scale trail leg toe elevation and clearance, despite straddling an obstacle for up to 2 min, similar to quadrupeds. Second, we found that when the lead leg was passively moved over an obstacle (eliminating an efference copy signal and altering proprioception) without vision, trail leg toe elevation and clearance were reduced, and variability increased compared with when subjects actively moved their lead leg. Trail leg toe measures returned to normal when vision was provided during the passive manipulation. Finally, we found that altering lead leg proprioceptive feedback by adding mass to the ankle had no effect on trail leg toe measures. Taken together, our results suggest that humans can store a neural representation of obstacle properties for extended periods of time and that vision appears to be sufficient in this process to guide trail leg trajectory. PMID- 22298833 TI - Efficient generation of reciprocal signals by inhibition. AB - Reciprocal activity between populations of neurons has been widely observed in the brain and is essential for neuronal computation. The different mechanisms by which reciprocal neuronal activity is generated remain to be established. A common motif in neuronal circuits is the presence of afferents that provide excitation to one set of principal neurons and, via interneurons, inhibition to a second set of principal neurons. This circuitry can be the substrate for generation of reciprocal signals. Here we demonstrate that this equivalent circuit in the cerebellar cortex enables the reciprocal firing rates of Purkinje cells to be efficiently generated from a common set of mossy fiber inputs. The activity of a mossy fiber is relayed to Purkinje cells positioned immediately above it by excitatory granule cells. The firing rates of these Purkinje cells increase as a linear function of mossy fiber, and thus granule cell, activity. In addition to exciting Purkinje cells positioned immediately above it, the activity of a mossy fiber is relayed to laterally positioned Purkinje cells by a disynaptic granule cell -> molecular layer interneuron pathway. Here we show in acutely prepared cerebellar slices that the input-output relationship of these laterally positioned Purkinje cells is linear and reciprocal to the first set. A similar linear input-output relationship between decreases in Purkinje cell firing and strength of stimulation of laterally positioned granule cells was also observed in vivo. Use of interneurons to generate reciprocal firing rates may be a common mechanism by which the brain generates reciprocal signals. PMID- 22298834 TI - Mechanical signals at the base of a rat vibrissa: the effect of intrinsic vibrissa curvature and implications for tactile exploration. AB - Rats actively tap and sweep their large mystacial vibrissae (whiskers) against objects to tactually explore their surroundings. When a vibrissa makes contact with an object, it bends, and this bending generates forces and bending moments at the vibrissa base. Researchers have only recently begun to quantify these mechanical variables. The present study quantifies the forces and bending moments at the vibrissa base with a quasi-static model of vibrissa deflection. The model was validated with experiments on real vibrissae. Initial simulations demonstrated that almost all vibrissa-object collisions during natural behavior will occur with the concave side of the vibrissa facing the object, and we therefore paid particular attention to the role of the vibrissa's intrinsic curvature in shaping the forces at the base. Both simulations and experiments showed that vibrissae with larger intrinsic curvatures will generate larger axial forces. Simulations also demonstrated that the range of forces and moments at the vibrissal base vary over approximately three orders of magnitude, depending on the location along the vibrissa at which object contact is made. Both simulations and experiments demonstrated that collisions in which the concave side of the vibrissa faces the object generate longer-duration contacts and larger net forces than collisions with the convex side. These results suggest that the orientation of the vibrissa's intrinsic curvature on the mystacial pad may increase forces during object contact and provide increased sensitivity to detailed surface features. PMID- 22298835 TI - Effect of gravity-like torque on goal-directed arm movements in microgravity. AB - Gravitational force level is well-known to influence arm motor control. Specifically, hyper- or microgravity environments drastically change pointing accuracy and kinematics, particularly during initial exposure. These modifications are thought to partly reflect impairment in arm position sense. Here we investigated whether applying normogravitational constraints at joint level during microgravity episodes of parabolic flights could restore movement accuracy equivalent to that observed on Earth. Subjects with eyes closed performed arm reaching movements toward predefined sagittal angular positions in four environment conditions: normogravity, hypergravity, microgravity, and microgravity with elastic bands attached to the arm to mimic gravity-like torque at the shoulder joint. We found that subjects overshot and undershot the target orientations in hypergravity and microgravity, respectively, relative to a normogravity baseline. Strikingly, adding gravity-like torque prior to and during movements performed in microgravity allowed subjects to be as accurate as in normogravity. In the former condition, arm movement kinematics, as notably illustrated by the relative time to peak velocity, were also unchanged relative to normogravity, whereas significant modifications were found in hyper- and microgravity. Overall, these results suggest that arm motor planning and control are tuned with respect to gravitational information issued from joint torque, which presumably enhances arm position sense and activates internal models optimally adapted to the gravitoinertial environment. PMID- 22298836 TI - Chemical screen reveals small molecules suppressing fragile X premutation rCGG repeat-mediated neurodegeneration in Drosophila. AB - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurodegenerative disorder recognized in fragile X premutation carriers. Using Drosophila, we previously identified elongated non-coding CGG repeats in FMR1 allele as the pathogenic cause of FXTAS. Here, we use this same FXTAS Drosophila model to conduct a chemical screen that reveals small molecules that can ameliorate the toxic effects of fragile X premutation ribo-CGG (rCGG) repeats, among them several known phospholipase A(2) (PLA(2)) inhibitors. We show that specific inhibition of PLA(2) activity could mitigate the neuronal deficits caused by fragile X premutation rCGG repeats, including lethality and locomotion deficits. Furthermore, through a genetic screen, we identified a PLA(2) Drosophila ortholog that specifically modulates rCGG repeat-mediated neuronal toxicity. Our results demonstrate the utility of Drosophila models for unbiased small molecule screens and point to PLA(2) as a possible therapeutic target to treat FXTAS. PMID- 22298837 TI - Quantifying the potential benefit of sigmoidoscopic rescreening for colorectal cancer. PMID- 22298838 TI - Flexible sigmoidoscopy in the randomized prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial: added yield from a second screening examination. AB - BACKGROUND: Among randomized trials evaluating flexible sigmoidoscopy (FSG) for its effect on colorectal cancer mortality, only the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial screened its participants more than one time. We report outcomes from the PLCO screening FSG program and evaluate the increased yield produced by a second FSG. METHODS: Participants were screened by 60-cm FSG in 10 regional screening centers at study entry and 3 or 5 years later, depending on the time of random assignment. Results from subsequent diagnostic intervention were tracked and recorded in a standardized fashion, and outcomes were compared according to sex and age. The protocol discouraged repeat FSG in persons with colorectal cancer or adenoma diagnosed after the initial FSG. RESULTS: Of 77 447 enrollees, 67 073 (86.6%) had at least one FSG and 39 443 (50.9%) had two FSGs. Diagnostic intervention occurred in 74.9% after a positive first FSG and in 78.7% after a positive repeat FSG. The second FSG increased the screening yield by 32%: Colorectal cancer or advanced adenoma was detected in 37.8 per 1000 persons after first screening and in 49.8 per 1000 persons after all screenings. The second FSG increased the yield of cancer or advanced adenoma by 26% in women and by 34% in men. Of 223 subjects who received a diagnosis of colorectal carcinoma within 1 year of a positive FSG, 64.6% had stage I and 17.5% had stage II disease. CONCLUSIONS: Repeat FSG increased the detection of colorectal cancer or advanced adenoma in women by one-fourth and in men by one third. Screen-detected carcinomas were early stage (stage I or II) in greater than 80% of screened persons. Colorectal cancer mortality data from the PLCO, as the definitive endpoint, will follow in later publications. PMID- 22298839 TI - A short exposure to polychlorinated biphenyls deregulates cellular autophagy in mammalian blastocyst in vitro. AB - BACKGROUND: Polychlorinated biphenyls (PCBs) are common environmental contaminants that represent an important risk factor of reproductive disorders in chronically exposed human populations. However, it is not known whether a short accidental exposure of embryos to PCBs before implantation might influence their further development and whether the effect might be reversible. METHODS AND RESULTS: To this aim, in vitro-matured sheep blastocysts were incubated with 2 or 4 ug/ml Aroclor 1254 (A1254), a mixture of 60 PCB congeners for 48 h after which blastocyst proliferation and ability for outgrowth in vitro were assessed. Blastocysts exposed to A1254 showed: (i) reduced proliferation and cell number (particularly in the inner cell mass compartment); (ii) accumulation of vacuoles and lipid droplets, diffused mitochondrial damage and up-regulation of autophagy markers (ATG6 and LC3), all signs indicative of deregulated autophagy, and (iii) massive cell death. Although exposed embryos resumed growth following A1254 removal, their subsequent development remained severely perturbed. CONCLUSIONS: These findings indicate that short exposure of blastocysts to PCBs leads to its damage characterized by deregulated autophagy and subsequent cell death. PMID- 22298840 TI - Selection against small males in utero: a test of the Wells hypothesis. AB - BACKGROUND: The argument that women in stressful environments spontaneously abort their least fit fetuses enjoys wide dissemination despite the fact that several of its most intuitive predictions remain untested. The literature includes no tests, for example, of the hypothesis that these mechanisms select against small for gestational age (SGA) males. METHODS: We apply time-series modeling to 4.9 million California male term births to test the hypothesis that the rate of SGA infants in 1096 weekly birth cohorts varies inversely with labor market contraction, a known stressor of contemporary populations. RESULTS: We find support for the hypothesis that small size becomes less frequent among term male infants when the labor market contracts. CONCLUSIONS: Our findings contribute to the evidence supporting selection in utero. They also suggest that research into the association between maternal stress and adverse birth outcomes should acknowledge the possibility that fetal loss may affect findings and their interpretation. Strengths of our analyses include the large number and size of our birth cohorts and our control for autocorrelation. Weaknesses include that we, like nearly all researchers in the field, have no direct measure of fetal loss. PMID- 22298841 TI - Cognitive and metabolic correlates of emotional vulnerability in patients with temporal lobe epilepsy. AB - BACKGROUND: Recent investigations have suggested that the occurrence of epileptic seizures is not completely random. In particular, various types of psychological changes or life events may act as triggering factors. OBJECTIVE: To identify a possible link between self-perception of the impact of affective precipitants, cognitive responses modulated by aversive information and brain metabolic modifications in patients with temporal lobe epilepsy (TLE). METHODS: The extent to which seizures were elicited or not by emotional precipitants was estimated using a self-reported scale, allowing distinction of two groups: 'Emo-TLE' group (patients reporting to have seizures triggered by emotional events) and 'Other TLE' group, which were compared with healthy individuals ('control' group). Attentional biases were investigated using the probe detection paradigm, using negative and neutral stimuli. Interictal brain metabolism was studied using FDG PET, and comparison was made between controls, Emo-TLE and Other-TLE groups. RESULTS: Patients with emotional vulnerability (Emo-TLE) disclosed specific attentional biases towards negative stimuli compared with the Other-TLE and control groups. Patients with Emo-TLE also exhibited specific hypometabolism in the anterior temporal lobe, including amygdala and hippocampus. The degree of attentional biases correlated with decreased metabolism in these regions. CONCLUSIONS: This investigation shows that the impact of affective events is the result of self-perception and also that it might be determined by specific cognitive and brain metabolic modifications in TLE. PMID- 22298842 TI - Flower colour adaptation in a mimetic orchid. AB - Although the tremendous variability in floral colour among angiosperms is often attributed to divergent selection by pollinators, it is usually difficult to preclude the possibility that floral colour shifts were driven by non-pollinator processes. Here, we examine the adaptive significance of flower colour in Disa ferruginea, a non-rewarding orchid that is thought to attract its butterfly pollinator by mimicking the flowers of sympatric nectar-producing species. Disa ferruginea has red flowers in the western part of its range and orange flowers in the eastern part--a colour shift that we hypothesized to be the outcome of selection for resemblance to different local nectar-producing plants. Using reciprocal translocations of red and orange phenotypes as well as arrays of artificial flowers, we found that the butterfly Aeropetes tulbaghia, the only pollinator of the orchid, preferred both the red phenotype and red artificial flowers in the west where its main nectar plant also has red flowers, and both the orange phenotype and orange artificial flowers in the east, where its main nectar plant has orange flowers. This phenotype by environment interaction demonstrates that the flower colour shift in D. ferruginea is adaptive and driven by local colour preference in its pollinator. PMID- 22298843 TI - Rejection of a serial founder effects model of genetic and linguistic coevolution. AB - Recent genetic studies attribute the negative correlation between population genetic diversity and distance from Africa to a serial founder effects (SFE) evolutionary process. A recent linguistic study concluded that a similar decay in phoneme inventories in human languages was also the product of the SFE process. However, the SFE process makes additional predictions for patterns of neutral genetic diversity, both within and between groups, that have not yet been tested on phonemic data. In this study, we describe these predictions and test them on linguistic and genetic samples. The linguistic sample consists of 725 widespread languages, which together contain 908 distinct phonemes. The genetic sample consists of 614 autosomal microsatellite loci in 100 widespread populations. All aspects of the genetic pattern are consistent with the predictions of SFE. In contrast, most of the predictions of SFE are violated for the phonemic data. We show that phoneme inventories provide information about recent contacts between languages. However, because phonemes change rapidly, they cannot provide information about more ancient evolutionary processes. PMID- 22298844 TI - Big hitting collectors make massive and disproportionate contribution to the discovery of plant species. AB - Discovering biological diversity is a fundamental goal--made urgent by the alarmingly high rate of extinction. We have compiled information from more than 100,000 type specimens to quantify the role of collectors in the discovery of plant diversity. Our results show that more than half of all type specimens were collected by less than 2 per cent of collectors. This highly skewed pattern has persisted through time. We demonstrate that a number of attributes are associated with prolific plant collectors: a long career with increasing productivity and experience in several countries and plant families. These results imply that funding a small number of expert plant collectors in the right geographical locations should be an important element in any effective strategy to find undiscovered plant species and complete the inventory of the world flora. PMID- 22298845 TI - Visual extrapolation under risk: human observers estimate and compensate for exogenous uncertainty. AB - Humans commonly face choices between multiple options with uncertain outcomes. Such situations occur in many contexts, from purely financial decisions (which shares should I buy?) to perceptuo-motor decisions between different actions (where should I aim my shot at goal?). Regardless of context, successful decision making requires that the uncertainty at the heart of the decision-making problem is taken into account. Here, we ask whether humans can recover an estimate of exogenous uncertainty and then use it to make good decisions. Observers viewed a small dot that moved erratically until it disappeared behind an occluder. We varied the size of the occluder and the unpredictability of the dot's path. The observer attempted to capture the dot as it emerged from behind the occluded region by setting the location and extent of a 'catcher' along the edge of the occluder. The reward for successfully catching the dot was reduced as the size of the catcher increased. We compared human performance with that of an agent maximizing expected gain and found that observers consistently selected catcher size close to this theoretical solution. These results suggest that humans are finely tuned to exogenous uncertainty information and can exploit it to guide action. PMID- 22298846 TI - The limits of brain determinacy. AB - The genes do not control everything that happens in a cell or an organism, because thermally induced molecular movements and conformation changes are beyond genetic control. The importance of uncontrolled events has been argued from the differences between isogenic organisms reared in virtually identical environments, but these might alternatively be attributed to subtle, undetected differences in the environment. The present review focuses on the uncontrolled events themselves in the context of the developing brain. These are considered at cellular and circuit levels because even if cellular physiology was perfectly controlled by the genes (which it is not), the interactions between different cells might still be uncoordinated. A further complication is that the brain contains mechanisms that buffer noise and others that amplify it. The final resultant of the battle between these contrary mechanisms is that developmental stochasticity is sufficiently low to make neurobehavioural defects uncommon, but a chance component of neural development remains. Thus, our brains and behaviour are not entirely determined by a combination of genes-plus-environment. PMID- 22298847 TI - The evolutionary history of haptophytes and cryptophytes: phylogenomic evidence for separate origins. AB - An important missing piece in the puzzle of how plastids spread across the eukaryotic tree of life is a robust evolutionary framework for the host lineages. Four assemblages are known to harbour plastids derived from red algae and, according to the controversial chromalveolate hypothesis, these all share a common ancestry. Phylogenomic analyses have consistently shown that stramenopiles and alveolates are closely related, but haptophytes and cryptophytes remain contentious; they have been proposed to branch together with several heterotrophic groups in the newly erected Hacrobia. Here, we tested this question by producing a large expressed sequence tag dataset for the katablepharid Roombia truncata, one of the last hacrobian lineages for which genome-level data are unavailable, and combined this dataset with the recently completed genome of the cryptophyte Guillardia theta to build an alignment composed of 258 genes. Our analyses strongly support haptophytes as sister to the SAR group, possibly together with telonemids and centrohelids. We also confirmed the common origin of katablepharids and cryptophytes, but these lineages were not related to other hacrobians; instead, they branch with plants. Our study resolves the evolutionary position of haptophytes, an ecologically critical component of the oceans, and proposes a new hypothesis for the origin of cryptophytes. PMID- 22298848 TI - Investigating sex-biased migration during the Neolithic transition in Europe, using an explicit spatial simulation framework. AB - Cultural practices can deeply influence genetic diversity patterns. The Neolithic transitions that took place at different times and locations around the world led to major cultural and demographic changes that influenced and therefore left their marks on human genetic diversity patterns. Several studies on the European Neolithic transition suggest that mitochondrial DNA (mtDNA) and Y-chromosome data can exhibit different patterns, which could be owing to different demographic histories for females and males. Archaeological and anthropological data suggest that the transition from hunter-gatherers (HGs) to farmers' societies is probably associated with changes in social organization, particularly in post-marital residence (PMR) rules (i.e. patrilocality, matrilocality or bilocality). The movements of humans and genes associated with these rules can be seen as sex biased short-range migrations. We developed a new individual-based simulation approach to explore the genetic consequences of 45 different scenarios, where we varied the patterns of PMR and admixture between HGs and farmers. We recorded mtDNA and Y-chromosome data and analysed their diversity patterns within and between populations, through time and space. We also collected published mtDNA and Y-chromosome data from European and Near-Eastern populations in order to identify the scenarios that would best explain them. We show that: (i) different PMR systems can lead to different patterns of genetic diversity and differentiation, (ii) asymmetries between mtDNA and Y-chromosome can be owing to different behaviours between males and females, but also to different mutations rates, and (iii) patrilocality in farmers explains the present patterns of genetic diversity better than matrilocality or bilocality. Moreover, we found that (iv) the genetic diversity of farmers change depending on the HGs PMR rules even though they are assumed to disappear more than 5000 years ago in our simulations. PMID- 22298849 TI - Linking genes to communities and ecosystems: Daphnia as an ecogenomic model. AB - How do genetic variation and evolutionary change in critical species affect the composition and functioning of populations, communities and ecosystems? Illuminating the links in the causal chain from genes up to ecosystems is a particularly exciting prospect now that the feedbacks between ecological and evolutionary changes are known to be bidirectional. Yet to fully explore phenomena that span multiple levels of the biological hierarchy requires model organisms and systems that feature a comprehensive triad of strong ecological interactions in nature, experimental tractability in diverse contexts and accessibility to modern genomic tools. The water flea Daphnia satisfies these criteria, and genomic approaches capitalizing on the pivotal role Daphnia plays in the functioning of pelagic freshwater food webs will enable investigations of eco-evolutionary dynamics in unprecedented detail. Because its ecology is profoundly influenced by both genetic polymorphism and phenotypic plasticity, Daphnia represents a model system with tremendous potential for developing a mechanistic understanding of the relationship between traits at the genetic, organismal and population levels, and consequences for community and ecosystem dynamics. Here, we highlight the combination of traits and ecological interactions that make Daphnia a definitive model system, focusing on the additional power and capabilities enabled by recent molecular and genomic advances. PMID- 22298850 TI - Rise of dinosaurs reveals major body-size transitions are driven by passive processes of trait evolution. AB - A major macroevolutionary question concerns how long-term patterns of body-size evolution are underpinned by smaller scale processes along lineages. One outstanding long-term transition is the replacement of basal therapsids (stem group mammals) by archosauromorphs, including dinosaurs, as the dominant large bodied terrestrial fauna during the Triassic (approx. 252-201 million years ago). This landmark event preceded more than 150 million years of archosauromorph dominance. We analyse a new body-size dataset of more than 400 therapsid and archosauromorph species spanning the Late Permian-Middle Jurassic. Maximum likelihood analyses indicate that Cope's rule (an active within-lineage trend of body-size increase) is extremely rare, despite conspicuous patterns of body-size turnover, and contrary to proposals that Cope's rule is central to vertebrate evolution. Instead, passive processes predominate in taxonomically and ecomorphologically more inclusive clades, with stasis common in less inclusive clades. Body-size limits are clade-dependent, suggesting intrinsic, biological factors are more important than the external environment. This clade-dependence is exemplified by maximum size of Middle-early Late Triassic archosauromorph predators exceeding that of contemporary herbivores, breaking a widely-accepted 'rule' that herbivore maximum size greatly exceeds carnivore maximum size. Archosauromorph and dinosaur dominance occurred via opportunistic replacement of therapsids following extinction, but were facilitated by higher archosauromorph growth rates. PMID- 22298851 TI - Drosophila melanogaster females change mating behaviour and offspring production based on social context. AB - In Drosophila melanogaster, biological rhythms, aggression and mating are modulated by group size and composition. However, the fitness significance of this group effect is unknown. By varying the composition of groups of males and females, we show that social context affects reproductive behaviour and offspring genetic diversity. Firstly, females mating with males from the same strain in the presence of males from a different strain are infecund, analogous to the Bruce effect in rodents, suggesting a social context-dependent inbreeding avoidance mechanism. Secondly, females mate more frequently in groups composed of males from more than one strain; this mitigates last male sperm precedence and increases offspring genetic diversity. However, smell-impaired Orco mutant females do not increase mating frequency according to group composition; this indicates that social context-dependent changes in reproductive behaviour depend on female olfaction, rather than direct male-male interactions. Further, variation in mating frequency in wild-type strains depends on females and not males. The data show that group composition can affect variance in the reproductive success of its members, and that females play a central role in this process. Social environment can thus influence the evolutionary process. PMID- 22298852 TI - Testosterone disrupts human collaboration by increasing egocentric choices. AB - Collaboration can provide benefits to the individual and the group across a variety of contexts. Even in simple perceptual tasks, the aggregation of individuals' personal information can enable enhanced group decision-making. However, in certain circumstances such collaboration can worsen performance, or even expose an individual to exploitation in economic tasks, and therefore a balance needs to be struck between a collaborative and a more egocentric disposition. Neurohumoral agents such as oxytocin are known to promote collaborative behaviours in economic tasks, but whether there are opponent agents, and whether these might even affect information aggregation without an economic component, is unknown. Here, we show that an androgen hormone, testosterone, acts as such an agent. Testosterone causally disrupted collaborative decision-making in a perceptual decision task, markedly reducing performance benefit individuals accrued from collaboration while leaving individual decision-making ability unaffected. This effect emerged because testosterone engendered more egocentric choices, manifest in an overweighting of one's own relative to others' judgements during joint decision-making. Our findings show that the biological control of social behaviour is dynamically regulated not only by modulators promoting, but also by those diminishing a propensity to collaborate. PMID- 22298853 TI - Skeletal development in the African elephant and ossification timing in placental mammals. AB - We provide here unique data on elephant skeletal ontogeny. We focus on the sequence of cranial and post-cranial ossification events during growth in the African elephant (Loxodonta africana). Previous analyses on ossification sequences in mammals have focused on monotremes, marsupials, boreoeutherian and xenarthran placentals. Here, we add data on ossification sequences in an afrotherian. We use two different methods to quantify sequence heterochrony: the sequence method and event-paring/Parsimov. Compared with other placentals, elephants show late ossifications of the basicranium, manual and pedal phalanges, and early ossifications of the ischium and metacarpals. Moreover, ossification in elephants starts very early and progresses rapidly. Specifically, the elephant exhibits the same percentage of bones showing an ossification centre at the end of the first third of its gestation period as the mouse and hamster have close to birth. Elephants show a number of features of their ossification patterns that differ from those of other placental mammals. The pattern of the initiation of the ossification evident in the African elephant underscores a possible correlation between the timing of ossification onset and gestation time throughout mammals. PMID- 22298854 TI - Disturbance-diversity models: what do they really predict and how are they tested? AB - The intermediate disturbance hypothesis (IDH) and the dynamic equilibrium model (DEM) are influential theories in ecology. The IDH predicts large species numbers at intermediate levels of disturbance and the DEM predicts that the effect of disturbance depends on the level of productivity. However, various indices of diversity are considered more commonly than the predicted number of species in tests of the hypotheses. This issue reaches beyond the scientific community as the predictions of the IDH and the DEM are used in the management of national parks and reserves. In order to compare responses with disturbance among measures of biodiversity, we used two different approaches of mathematical modelling and conducted an extensive meta-analysis. Two-thirds of the surveyed studies present different results for different diversity measures. Accordingly, the meta analysis showed a narrow range of negative quadratic regression components for richness, but not evenness. Also, the two models support the IDH and the DEM, respectively, when biodiversity is measured as species richness, but predict evenness to increase with increasing disturbance, for all levels of productivity. Consequently, studies that use compound indices of diversity should present logical arguments, a priori, to why a specific index of diversity should peak in response to disturbance. PMID- 22298855 TI - Orbital prefrontal cortex volume predicts social network size: an imaging study of individual differences in humans. AB - The social brain hypothesis, an explanation for the unusually large brains of primates, posits that the size of social group typical of a species is directly related to the volume of its neocortex. To test whether this hypothesis also applies at the within-species level, we applied the Cavalieri method of stereology in conjunction with point counting on magnetic resonance images to determine the volume of prefrontal cortex (PFC) subfields, including dorsal and orbital regions. Path analysis in a sample of 40 healthy adult humans revealed a significant linear relationship between orbital (but not dorsal) PFC volume and the size of subjects' social networks that was mediated by individual intentionality (mentalizing) competences. The results support the social brain hypothesis by indicating a relationship between PFC volume and social network size that applies within species, and, more importantly, indicates that the relationship is mediated by social cognitive skills. PMID- 22298856 TI - Foraging costs drive female resistance to a sensory trap. AB - Male ornaments can evolve through the exploitation of female perceptual biases such as those involved in responding to cues from food. This type of sensory exploitation may lead to confusion between the male signals and the cues that females use to find/recognize food. Such interference would be costly to females and may be one reason why females evolve resistance to the male ornaments. Using a group of species of viviparous fish where resistance to a sensory trap has evolved, we demonstrate that females exposed to an ornament that resembles food have a diminished foraging efficiency, that this effect is apparent when foraging on a food item with which the ornament shares visual attributes, and that not all species are equally affected by such confusion. Our results lend support to the model of ornamental evolution through chase-away sexual conflict. PMID- 22298857 TI - Very low survival rates after non-traumatic lower limb amputation in a consecutive series: what to do? AB - The aim of this retrospective study was to evaluate factors potentially influencing short- and long-term mortality in patients who had a non-traumatic lower limb amputation in a university hospital. A consecutive series of 93 amputations (16% toe/foot, 33% trans-tibial, 9% through knee and 42% trans femoral) were studied. Their mean age was 75.8 years; 21 (23%) were admitted from a nursing home and 87 (92%) were amputated due to a vascular disease and/or diabetes. Thirty days and 1-year mortality were 30 and 54%, respectively. Cox regression analysis demonstrated that the 30-day mortality was associated with older age (P = 0.01), and the number of co-morbidities (P = 0.04), when adjusted for gender, previous amputations, cause of and amputation level, and residential status. Thus, a patient with 4 or 5 co-morbidities (n = 20) was seven times more likely to die within 30 days, compared with a patient with 1 co-morbidity (n = 16). Further, the risk of not surviving increased with 7% per each additional year the patient got older. Of concern, almost one-third of patients died within 1 month. This may be unavoidable, but a multidisciplinary, optimized, multimodal pre- and postoperative programme should be instituted, trying to improve the outcome. PMID- 22298858 TI - Isolated aortic root dilatation following sinotubular junction reduction using prosthetic rings. AB - 'Comprehensive Aortic Root and Valve Reconstruction' technique, which was first introduced in 2005 involves aortic root reduction using prosthetic rings in order to preserve the native aortic sinuses in patients having aortic regurgitation associated with aortic root dilatation. We report a case of isolated aortic sinus aneurysm in a Marfan syndrome patient following the aortic root preserving surgery in the presence of ascending aorta aneurysm and annuloaortic ectasia. Re operation consisted of aortic sinus resection and replacement with an artificial graft, and coronary reimplantation using a button technique. Close follow-up is essential for patients who underwent aortic root preserving surgery to appropriately manage this kind of complication. PMID- 22298859 TI - Sound judgment. PMID- 22298860 TI - The sound judgment series. PMID- 22298861 TI - Assessment of substantia nigra echogenicity in German and Filipino populations using a portable ultrasound system. AB - OBJECTIVES: Transcranial sonography of the substantia nigra for diagnosing premotor stages of Parkinson disease has been attracting increasing interest. Standard reference values defining an abnormal increased echogenic size (hyperechogenicity) of the substantia nigra have been established in several populations using high-end stationary ultrasound systems. It is unknown whether a portable ultrasound system can be appropriately used and how the Filipino population would compare with the well-studied white population. METHODS: We prospectively studied substantia nigra echogenic sizes and third ventricle widths in 71 healthy adult German participants and 30 age- and sex-matched Filipino participants using both a well-established stationary ultrasound system (in the German cohort) and a recently distributed portable ultrasound system (in both ethnic cohorts). RESULTS: Mean substantia nigra echogenic sizes, cutoff values defining abnormal hyperechogenicity, and intra-rater reliability were similar with both systems and in both ethnic cohorts studied. The Filipino and German participants did not differ with respect to the frequency of insufficient insonation conditions (each 3%) and substantia nigra hyperechogenicity (10% versus 9%; P = .80). However, third ventricle widths were smaller in the Filipino than the German participants (mean +/- SD, 1.6 +/- 1.1 versus 2.4 +/- 1.0 mm; P = .004). CONCLUSIONS: The frequency of substantia nigra hyperechogenicity appears to be homogeneous in white and Asian populations. Screening for this feature may well be performed with a present-day portable ultrasound system. PMID- 22298862 TI - Differentiating benign from malignant thyroid nodules: comparison of 2- and 3- dimensional sonography. AB - OBJECTIVES: To compare the diagnostic performance of radiologists and to determine interobserver and intraobserver variability with regard to differentiation of benign and malignant thyroid nodules using prospectively obtained 2-dimensional (2D) and 3-dimensional (3D) sonograms. METHODS: This study had Institutional Review Board approval, and the requirement for patient informed consent was waived. Conventional 2D and 3D sonograms were obtained from 82 patients (age range, 20-77 years; mean age, 51 years) with 91 thyroid nodules (15 cancers, 13 indeterminate, and 63 benign lesions) before diagnostic fine-needle aspiration. Three radiologists reviewed stored 2D and 3D images for internal content, shape, margin, echogenicity, echo texture, and the presence of calcification and estimated the level of suspicion as to the probability of malignancy according to known sonographic criteria. The diagnostic performance of 2D images was compared with that of 3D images. RESULTS: For all readers, interpretation using 3D images was more sensitive and specific than that using 2D images for diagnosis of malignant thyroid nodules, with the exception of specificity for reader 1. However, differences were not statistically significant (P > .05). Area under the receiver operating characteristic curve values were 0.83 for 2D images and 0.92 for 3D images for reader 1; 0.78 for 2D images and 0.89 for 3D images for reader 2; and 0.89 for 2D images and 0.93 for 3D images for reader 3. Interobserver agreement between the 3 radiologists for differentiation of benign and malignant thyroid nodules was better for 3D images (kappa = 0.49) than for 2D images (kappa = 0.15). Intraobserver variability for nodule descriptions and assessments using 3D and 2D images was fair to moderate. CONCLUSION: The performance of radiologists and interobserver and intraobserver agreement for characterization of thyroid nodules were better when 3D sonograms were used than when 2D sonograms were used. PMID- 22298863 TI - Reference values for the length and area of the fetal corpus callosum on 3 dimensional sonography using the transfrontal view. AB - OBJECTIVES: The purpose of this study was to determine reference values for the length and area of the fetal corpus callosum between 20 and 33 weeks' gestation using 3-dimensional sonography. METHODS: A cross-sectional study was performed in 293 healthy pregnant women between 20 and 33 weeks' gestation. The length and area of the corpus callosum were obtained via the transfontal view with the metopic suture as an acoustic window using 3-dimensional sonographic aquisitions. Linear and weighted polynomial regression models were used, which were adjusted by residual analysis and the R(2) determination coefficient. Intraobserver and interobserver reproducibilities were analyzed by an intraclass correlation coefficient. RESULTS: The mean corpus callosum length +/- SD varied from 19.52 +/ 2.24 to 40.36 +/- 2.87 mm, whereas the mean area varied from 0.44 +/- 0.11 to 1.47 +/- 0.21 cm(2) at 20 and 33 weeks, respectively. The length and area were highly correlated with gestational age: corpus callosum length = -52.41 + 4.71 * gestational age - 0.06 * gestational age(2) (R(2) = 0.868); and corpus callosum area = -2.47 + 0.16 * gestational age - 0.000037 * gestational age(2) (R(2) = 0.765). The intraobserver and interobserver reproducibilities were excellent, with intraclass correlation coefficients of 0.98 and 0.94 for the length and 0.99 and 0.90 for the area, respectively. CONCLUSIONS: Reference values for the length and the area of the fetal corpus callosum between 20 and 33 weeks' gestation were determined with high reproducibility. PMID- 22298864 TI - Placental thickness in the second trimester: a pilot study to determine the normal range. AB - OBJECTIVES: We sought to determine the normal sonographically measured placental thickness in millimeters at the second-trimester scan (18 weeks to 22 weeks 6 days) and determine whether the measurement should be adjusted for gestational age and the placental site. METHODS: We conducted a cross-sectional observational pilot study involving 114 consecutive patients with singleton pregnancies presenting for routine second-trimester sonography between 18 weeks and 22 weeks 6 days. RESULTS: The unadjusted overall mean placental thickness was 24.6 (SD, 7.29) mm. The placental thickness was normally distributed. On multivariable analysis, the predicted mean thickness was 6.6 mm (95% confidence interval, 4.4 to 8.8 mm; P < .001) less in anterior compared to posterior or fundal placentas and increased by 0.6 mm (95% confidence interval, -0.5 to 1.7 mm; P = .27) for each week increase in gestation after 18 weeks CONCLUSIONS: The placental position and possibly gestational age need to be considered when determining placental thickness. Anterior placentas are approximately 7 mm thinner than posterior or fundal placentas. Anterior placentas of greater than 33 mm and posterior placentas of greater than 40 mm should be considered abnormally thick. PMID- 22298865 TI - Adaptive changes in the splenic artery and left portal vein in fetal growth restriction. AB - OBJECTIVES: The purpose of this study was to determine whether a low splenic artery pulsatility index (PI) and reduced flow through the left portal vein are involved in redistribution of fetal growth restriction. METHODS: Forty-two women with prenatally diagnosed intrauterine growth restriction of singleton fetuses were included. The next pregnant woman with an appropriately growing fetus, matched for gestational age, was selected as a control. Blood flow velocities were measured in the splenic artery and left portal vein. Obstetric and perinatal information was obtained from standardized medical records. RESULTS: The blood flow through the left portal vein was significantly reduced compared with the controls (P < .0001). Placental impairment in fetal growth restriction was clearly linked to a decreased splenic artery PI (P = .0004). In growth-restricted fetuses with reduced left portal vein flow and a splenic artery PI below the 5th percentile, perinatal mortality, a low 5-minute Apgar score, and neonatal metabolic acidosis were observed significantly more often (P = .04, .01, and .004; P = .03, .03, and .006, respectively). CONCLUSIONS: Reduced blood flow through the left portal vein and low resistance in the splenic artery can be found in growth-restricted fetuses with adverse neonatal outcomes. PMID- 22298866 TI - Early visualization and measurement of the pericallosal artery: an indirect sign of corpus callosum development. AB - OBJECTIVES: The purpose of this study was to evaluate the feasibility of visualization and measurement of the pericallosal artery during early stages of gestation. METHODS: The study group comprised 80 pregnant women between 12 and 21 weeks' gestation who attended our ultrasound unit. Transabdominal or transvaginal sonography was performed to obtain the optimal angle of a midsagittal section. High-definition flow power Doppler imaging was used to visualize the pericallosal artery. In a sagittal plane, the lengths of the pericallosal artery were measured using a straight line to connect the most anterior and posterior points. All patients were reexamined at a later stage of pregnancy to verify the existence of the corpus callosum and pericallosal artery. RESULTS: Visualization of the pericallosal artery was evident in 71 fetuses, in all of whom the biparietal diameter was greater than 20 mm. We were able to verify normal anatomy and the existence of the pericallosal artery in these fetuses between 30 and 32 weeks' gestation. A positive linear association was found between the length of the pericallosal artery and the gestational age (R(2) = 0.95) and the biparietal diameter at each gestational age (R(2) = 0.99). CONCLUSIONS: Our data show that it is feasible to visualize and measure the pericallosal artery from an early stage of gestation, and this measurement could be an indirect indication of normal corpus callosum development. PMID- 22298867 TI - Maternal hydration therapy improves the quantity of amniotic fluid and the pregnancy outcome in third-trimester isolated oligohydramnios: a controlled randomized institutional trial. AB - OBJECTIVES: Amniotic fluid is important for the maintenance of fetal well-being; therefore, an amniotic fluid deficiency, ie, oligohydramnios, can have multiple impacts on the prognosis of the pregnancy. In some cases, there are no evident fetal or maternal causes, and the condition is called isolated oligohydramnios. The aim of our study was to validate maternal intravenous and oral hydration therapy as a means for improvement of isolated oligohydramnios in the third trimester of pregnancy. METHODS: We conducted a prospective randomized controlled study on pregnancies complicated by idiopathic oligohydramnios (group A, 66 women) with a control group of women with normal pregnancies without oligohydramnios (group B, 71 women). Oligohydramnios was diagnosed using the amniotic fluid index (AFI; <5 cm). Sonographic examinations were performed with a convex 3.5-MHz probe. Group A underwent 6 days of intravenous infusion of 1500 mL of an isotonic solution per day. An AFI measurement, a nonstress test, and a fetal biophysical profile were performed at 0 and 7 days. Group A was randomized into subgroups A1 and A2. Subgroup A1 was prescribed home oral hydration therapy of 1500 mL/d and subgroup A2 2500 mL/d. We considered the AFI to compare the effectiveness of the therapy. RESULTS: General features did not reveal any significant differences between the two groups. In group A, the mean AFI +/- SD at recruitment was 39.68 +/- 11.11 mm; in group B, it was 126.92 +/- 10.59 mm (P < .001). In group A, the mean AFI at 7 days was 77.70 +/- 15.03 mm; in group B, it was unchanged. In subgroup A1, the mean AFI at birth was 86.21 +/- 16.89 mm; in subgroup A2, it was 112.45 +/- 14.92 mm (P < .001). CONCLUSIONS: Our data show that in pregnancies complicated by isolated oligohydramnios, hydration therapy significantly improves the quantity of amniotic fluid. PMID- 22298868 TI - First in vivo use of a capacitive micromachined ultrasound transducer array-based imaging and ablation catheter. AB - OBJECTIVES: The primary objective was to test in vivo for the first time the general operation of a new multifunctional intracardiac echocardiography (ICE) catheter constructed with a microlinear capacitive micromachined ultrasound transducer (ML-CMUT) imaging array. Secondarily, we examined the compatibility of this catheter with electroanatomic mapping (EAM) guidance and also as a radiofrequency ablation (RFA) catheter. Preliminary thermal strain imaging (TSI) derived temperature data were obtained from within the endocardium simultaneously during RFA to show the feasibility of direct ablation guidance procedures. METHODS: The new 9F forward-looking ICE catheter was constructed with 3 complementary technologies: a CMUT imaging array with a custom electronic array buffer, catheter surface electrodes for EAM guidance, and a special ablation tip, that permits simultaneous TSI and RFA. In vivo imaging studies of 5 anesthetized porcine models with 5 CMUT catheters were performed. RESULTS: The ML-CMUT ICE catheter provided high-resolution real-time wideband 2-dimensional (2D) images at greater than 8 MHz and is capable of both RFA and EAM guidance. Although the 24 element array aperture dimension is only 1.5 mm, the imaging depth of penetration is greater than 30 mm. The specially designed ultrasound-compatible metalized plastic tip allowed simultaneous imaging during ablation and direct acquisition of TSI data for tissue ablation temperatures. Postprocessing analysis showed a first-order correlation between TSI and temperature, permitting early development temperature-time relationships at specific myocardial ablation sites. CONCLUSIONS: Multifunctional forward-looking ML-CMUT ICE catheters, with simultaneous intracardiac guidance, ultrasound imaging, and RFA, may offer a new means to improve interventional ablation procedures. PMID- 22298869 TI - Solid pseudopapillary tumors of the pancreas: contrast-enhanced sonographic features. AB - OBJECTIVES: The aims of this study were to determine the features of solid pseudopapillary tumors of the pancreas on contrast-enhanced sonography and correlate them with pathologic findings. METHODS: Five patients with solid pseudopapillary tumors of the pancreas underwent conventional sonographic, color Doppler flow imaging, and contrast-enhanced sonographic examinations. Time intensity curves were used to calculate the contrast enhancement times, wash-out times, and enhancement patterns of the lesions. Three of the 5 patients also underwent contrast-enhanced computed tomography. All cases were confirmed by surgery and pathologic examination. RESULTS: The study included 3 women and 2 men. Tumor diameters ranged from 4.4 to 13.0 cm. Sonography revealed round well defined encapsulated tumors. Two appeared as mixed cystic-solid and 3 as solid masses on conventional sonography. One mass had a macrocalcification. Some areas of blood flow were seen in 3 of the masses on color Doppler flow imaging. On contrast-enhanced sonography, the peripheral rims of the tumors showed isoenhancement during the early arterial phase, and the interiors of the masses showed heterogeneous enhancement consisting of regions of isoenhancement, hypoenhancement, and nonenhancement. Progressive wash-out of the contrast agent during venous phases revealed hypoenhancement compared with normal adjacent pancreatic parenchyma. Pathologic findings showed that each tumor was completely encapsulated and had varying degrees of internal hemorrhage and necrosis. CONCLUSIONS: Solid pseudopapillary tumors of the pancreas have characteristic findings on contrast-enhanced sonography, including peripheral rim isoenhancement and internal heterogeneous enhancement with nonenhanced portions; these features may help differentiate solid pseudopapillary tumors from other pancreatic neoplasms. PMID- 22298870 TI - Differences in sonographic features of ruptured and unruptured epidermal cysts. AB - OBJECTIVES: This study aimed to report the differences in sonographic features of ruptured and unruptured epidermal cysts. METHODS: We reviewed and analyzed the sonographic features of superficial epidermal cysts of in 2 subgroups of 46 patients: 20 with ruptured cysts and 26 with unruptured cysts. All lesions were diagnosed either by excisional biopsy or by debridement biopsy. Sonographic features used in the analysis included tumor size, location, echo texture, pericystic changes, boundary, and shape on gray scale sonography and lesion vascularity on color Doppler sonography. Pathologic examinations were reviewed with emphasis on differences between ruptured and unruptured epidermal cysts. RESULTS: Unruptured epidermal cysts showed significantly higher frequencies of an oval shape, presence of a halo, well-circumscribed boundaries, and lack of blood flow signals (P < .05). In contrast, ruptured cysts usually had a lobulated shape, a slightly poorly defined or poorly defined boundary, the absence of a halo, and intermediate grades of lesion vascularity. The lesion sizes and sonographic features, including dermal attachment, a hypoechoic echo texture, posterior acoustic enhancement, and the presence of intralesional hyperechoic strips and hypoechoic debris, showed no significant differences between the groups (P > .05). In pathologic studies, acute and chronic inflammatory reactions, more prominent microvessels, and abscess formation in the adjacent stromal tissue, the lesions, or both could be detected in the 20 ruptured epidermal cysts but not in the unruptured cysts. CONCLUSIONS: This research shows that recognition of different sonographic features is helpful for differentiating ruptured and unruptured epidermal cysts. PMID- 22298871 TI - Breast sonographic elastography using an advanced breast tissue-specific imaging preset: initial clinical results. AB - OBJECTIVES: The purpose of this study was to evaluate the interpretation criteria, such as the size ratio, stain ratio, and elasticity score, and to assess the diagnostic performance of sonographic elastography by using an advanced breast tissue-specific imaging preset compared with that of conventional sonography for the differentiation of benign and malignant breast masses. METHODS: Conventional sonography and sonographic elastography with the tissue specific imaging preset were performed in 104 patients (age range, 17-76 years; mean age, 47.7 years) with 110 breast lesions (67 benign and 43 malignant; mean size, 1.69 cm). The data from the interpretation criteria of sonographic elastography were obtained. The pathologic results from surgical excision or vacuum-assisted removal were used as a reference standard. RESULTS: The values for the area under the receiver operating characteristic curve were 0.959 (95% confidence interval [CI], 0.902-0.987) for conventional sonography and 0.901 (95% CI, 0.829-0.949), 0.796 (95% CI, 0.708-0.866), and 0.787 (95% CI, 0.699-0.859) for the strain ratio, size ratio, and elasticity score, respectively. When a strain ratio cutoff point of 4.215 was used, the sensitivity and specificity were 86.0% and 85.1%. With a best cutoff point for conventional sonography between Breast Imaging Reporting and Data System categories 4A and 4B, the sensitivity and specificity were 93.0% and 83.6%. CONCLUSIONS: The strain ratio showed the best diagnostic performance among the interpretation criteria for sonographic elastography with the tissue-specific imaging preset. The diagnostic performance was slightly higher for Breast Imaging Reporting and Data System categories than for the strain ratio. However, there was no statistical significance (P = .052). PMID- 22298872 TI - Evaluation of breast lesions using sonographic elasticity imaging: a multicenter trial. AB - OBJECTIVES: The purpose of this study was to determine the sensitivity and specificity of real-time compression elasticity imaging in characterizing breast lesions as benign or malignant. METHODS: A cohort of 578 women scheduled for sonographically guided biopsy of breast lesions were recruited from 6 sites under an Institutional Review Board-approved protocol. All participants received an elastogram, which displayed both the B-mode and elasticity images in real time. The longest dimensions of the lesion on the B-mode and elasticity imaging were measured. An elasticity imaging/B-mode ratio of at least 1.0 was considered positive for malignant lesions. The reference standard was based on biopsy. RESULTS: A total of 635 lesions were imaged and biopsied. There were 222 (35%) malignant or borderline lesions and 413 (65%) benign lesions. The benign lesions were either cystic (145 [35%]) or solid (268 [65%]). Of the 222 malignant lesions, 219 had an elasticity imaging/B-mode ratio of at least 1.0. Of the 413 benign lesions, 361 had an elasticity imaging/B-mode ratio less than 1.0. These results corresponded to overall sensitivity of 98.6% and overall specificity of 87.4%. Individual site sensitivities ranged from 96.7% to 100% whereas specificities ranged from 66.7% to 95.4%. CONCLUSIONS: Elasticity imaging has high sensitivity in characterizing malignant lesions of the breast. Variability in specificity between sites and sonographers is possibly due to individual technique differences in performing elastography and measuring lesions. Further work in standardizing the technique is required. PMID- 22298873 TI - Virtual touch tissue quantification using acoustic radiation force impulse technology: initial clinical experience with solid breast masses. AB - OBJECTIVES: The purpose of this study was to investigate the clinical usage of Virtual Touch tissue quantification (VTQ; Siemens Medical Solutions, Mountain View, CA) implementing sonographic acoustic radiation force impulse technology for differentiation between benign and malignant solid breast masses. METHODS: A total of 143 solid breast masses were examined with VTQ, and their shear wave velocities (SWVs) were measured. From all of the masses, 30 were examined by two independent operators to evaluate the reproducibility of the results of VTQ measurement. All masses were later surgically resected, and the histologic results were correlated with the SWV results. A receiver operating characteristic curve was calculated to assess the diagnostic performance of VTQ. RESULTS: A total of 102 benign lesions and 41 carcinomas were diagnosed on the basis of histologic examination. The VTQ measurements performed by the two independent operators yielded a correlation coefficient of 0.885. Applying a cutoff point of 3.065 m/s, a significant difference (P < .001) was found between the SWVs of the benign (mean +/- SD, 2.25 +/- 0.59 m/s) and malignant (5.96 +/- 2.96 m/s) masses. The sensitivity, specificity, and area under the receiver operating characteristic curve for the differentiation were 75.6%, 95.1%, and 85.6%, respectively. When the repeated non-numeric result X.XX of the SWV measurements was designated as an indicator of malignancy, the sensitivity, specificity, and accuracy were 63.4%, 100%, and 89.5%. CONCLUSIONS: Virtual Touch tissue quantification can yield reproducible and quantitative diagnostic information on solid breast masses and serve as an effective diagnostic tool for differentiation between benign and malignant solid masses. PMID- 22298874 TI - I-AIM: a novel model for teaching and performing focused sonography. AB - This project was designed to use existing evidence in education and clinical quality improvement to design an educational and clinical model specific for physician-performed focused sonography. The I-AIM model (indication, acquisition, interpretation, and medical decision making) was created to serve as both a mnemonic and checklist. The model follows a stepwise logic for performing focused sonographic examinations and contains detailed subcomponent listings that cover specific areas to improve use and performance. Although validation and reliability studies will be required before implementation, the I-AIM model represents the first effort to standardize and improve clinical and educational focused-sonography. PMID- 22298875 TI - Common sonographic findings in the painful hip after hip arthroplasty. AB - Diagnosing the cause of hip pain in patients with hip arthroplasty can be challenging because of the numerous possible causes of pain and artifacts caused by the prosthetic components on computed tomography and magnetic resonance imaging. Sonography plays an important role in the diagnosis and management of these patients because the soft tissues surrounding the prosthetic joint are not obscured by artifacts and because sonography enables hands-on examination of the painful site, dynamic evaluation of moving structures, and comparison with the opposite side. Another advantage of sonography is the ability to perform sonographically guided diagnostic and therapeutic procedures. In this pictorial essay, we highlight commonly encountered sonographic findings in patients with hip pain after hip arthroplasty. PMID- 22298876 TI - OmniView algorithm: a novel 3-dimensional sonographic technique in the study of the fetal hard and soft palates. AB - The purpose of this pictorial essay is to report on the application of OmniView (GE Healthcare, Zipf, Austria), new 3-dimensional sonographic software, and its application in the prenatal sonographic study of the fetal hard and soft palates. We will show that this novel technique is easy and feasible, requires a limited learning curve, and provides correct volume interrogation of the region of interest. The OmniView algorithm may be useful in training programs, and volume data sets can be interpreted by experts in remote sites. Future prospective studies with consecutive patients will be necessary to evaluate whether the routine application of OmniView will increase the prenatal diagnosis of facial clefting, especially those with isolated palate defects. PMID- 22298877 TI - The unicornuate uterus and its variants: clinical presentation, imaging findings, and associated complications. AB - This article will describe the different variants of the unicornuate uterus, their clinical presentation and imaging findings, as well their associated complications. We will also review the associated renal anomalies. Patients' symptoms and their imaging findings will vary depending on the unicornuate subtype. Radiologic evaluation includes a combination of hysterosalpingography, sonography, and magnetic resonance imaging. Complications include obstetric ones related to the small uterine size and endometriosis and ectopic pregnancies when a cavitary rudimentary uterine horn is present. Radiologists should be familiar with all variants of the unicornuate uterus as well as their clinical presentation and associated imaging findings. PMID- 22298878 TI - Sonography in postmenopausal bleeding. PMID- 22298879 TI - Choroid plexus carcinoma: prenatal characterization by 3-dimensional sonography and magnetic resonance imaging, perinatal management, and natural history. PMID- 22298880 TI - Three-dimensional surface rendering of the chorionic placental plate: the "tire" sign for the diagnosis of a circumvallate placenta. PMID- 22298881 TI - Identification and immunogenicity of two new HLA-A*0201-restricted CD8+ T-cell epitopes on dengue NS1 protein. AB - Immunopathogenesis of dengue virus (DEN) infection remains poorly studied. Identification and characterization of human CD8(+) T-cell epitopes on DEN are necessary for a better understanding of the immunopathogenesis of dengue infection and would facilitate the development of immunotherapy and vaccines to protect from dengue infection. Here, we identified two new HLA-A*0201-restricted CD8(+) T-cell epitopes, DEN-4 NS1(990)(-998) and DEN-4 NS1(997)(-1005) that are conserved in three or four major DEN serotypes, respectively. Unexpectedly, we found that immunization of HLA-A*0201 transgenic mice with DEN-4 NS1(990)(-998) or DEN-4 NS1(997)(-1005) epitope peptide induced de novo synthesis of tumor necrosis factor (TNF)-alpha and IFN-gamma, two important pro-inflammatory molecules that are hard to be detected directly without in vitro antigenic re stimulation. Importantly, we demonstrated that CD8(+) T cells specifically activated by DEN-4 NS1(990)(-998) or DEN-4 NS1(997)(-1005) epitope peptide induced de novo synthesis of perforin. Furthermore, we observed that DEN-4 NS1(990)(-998) or DEN-4 NS1(997)(-1005)-specific CD8(+) T cells capable of producing large amounts of perforin, TNF-alpha and IFN-gamma preferentially displayed CD27(+)CD45RA(-), but not CD27(-)CD45RA(+), phenotypes. This study, therefore, suggested the importance of synergistic effects of pro-inflammatory cytokines and cytotoxic molecules which were produced by dengue-specific CD8(+) T cells in immunopathogenesis or anti-dengue immunity during dengue infection. PMID- 22298882 TI - Integrin alpha1/beta1 and alpha2/beta1 as a receptor for IgA1 in human glomerular mesangial cells in IgA nephropathy. AB - IgA nephropathy (IgAN) is characterized by mesangial deposition of IgA1 and galactose-deficient IgA1 is expected to play a pathogenic role. However, the identity of the receptor for IgA1 is still controversial. Hence, the aim of this study was to explore the receptor for galactose-deficient IgA1. Human monoclonal IgA1 was treated with exoglycosidase and FITC-conjugated control, asialo- and agalactosyl-IgA1 was used as a probe to detect the receptor in cultured human mesangial cells. Tumor necrosis factor-alpha or transforming growth factor-beta1 treatment accelerated IgA1-binding on mesangial cells, and these effects were diminished by the addition of dexamethasone, whereas these changes were not dependent on galactose-deficiency of IgA1. According to comprehensive gene expression analysis, we focused on integrin beta1. Pre-treatment by Mn(2+), which activates integrin by changing its structure, enhanced the binding of IgA1 in cultured mesangial cells. Furthermore, pre-incubation with collagens specifically enhanced binding of IgA1 in the cultured human mesangial cells without activation by Mn(2+). Collagen type IV distributed in the mesangial region of the glomeruli as well as Bowman's capsule and tubular basal membrane in IgAN patients, and the IgA1 with collagen type IV induced proliferative signals on mesangial cells by phosphorylating extracellular signal-regulated kinase more effectively than the IgA1 alone. Immunoprecipitation assay revealed the binding of IgA1 and integrin alpha1/beta1 and alpha2/beta1 heterodimer and down-regulation of integrin alpha1, alpha2 and beta1 expression in human mesangial cells induced by each specific small interfering RNA diminished the ability to bind IgA1 probe. Integrin alpha1/beta1 and alpha2/beta1 would be a candidate receptor for IgA1. PMID- 22298883 TI - Transient depletion of B cells in young mice results in activation of regulatory T cells that inhibit development of autoimmune disease in adults. AB - B-cell depletion therapy can be effective for treating B-cell lymphomas as well as many human and murine autoimmune diseases. B-cell-deficient mice are normally resistant to spontaneous autoimmune thyroiditis (SAT), but they develop SAT if regulatory T cells are transiently depleted during the first 3-6 weeks after birth. This was also a critical time when B-cell depletion effectively inhibited development of SAT in adult mice. The current study was undertaken to test the hypothesis that transient depletion of B cells using anti-CD20 would be sufficient to suppress SAT if B cells were depleted early in life and that inhibition of SAT would be due to the activity of Treg that functioned most effectively when B cells were absent or low. The results presented here support this hypothesis and indicate that development of autoimmune disease in adults is effectively inhibited when anti-CD20 is administered 1-3 weeks after birth. After 3 weeks, transient B-cell depletion is no longer effective, and B-cell depletion must be maintained to effectively suppress autoimmune disease. B-cell depletion in 1- to 3-week-old mice depletes all B-cell subsets, whereas B-cell depletion initiated in adults spares many marginal zone B cells. Following early B-cell depletion, splenic Treg increase in number, and depletion of Treg reverses the inhibitory effect of anti-CD20 on disease development. Early transient depletion of B cells could be useful for preventing autoimmune disease in individuals at high risk for developing autoimmune diseases as adults. PMID- 22298884 TI - Association of the level of IFN-gamma produced by T cells in response to Mycobacterium tuberculosis-specific antigens with the size of skin test indurations among individuals with latent tuberculosis in a highly tuberculosis endemic setting. AB - There is growing evidence showing the potential of T-cell-based gamma interferon (IFN-gamma) release assays (IGRAs) for predicting the risk of progression of Mycobacterium tuberculosis (Mtb) infection, though there is little information from tuberculosis (TB)-endemic settings. In this study, we assessed the association between the level of IFN-gamma produced by T cells in response to Mtb specific antigens and the size of skin test indurations in 505 adult individuals who were screened for latent tuberculosis infection (LTBI) using the QuantiFERON TB Gold In Tube (QFTGIT) assay and tuberculin skin test (TST). There was a strong positive correlation between the level of IFN-gamma induced by the specific antigens and the diameter of the skin indurations (Spearman's rho = 0.6, P < 0.001). Body mass index and parasitic infection were not associated with the level of IFN-gamma production or the TST reaction. In linear regression analysis, the size of the skin test indurations was significantly associated with the mean level of IFN-gamma [coefficient, 0.65; 95% confidence interval (CI), 0.47 to 0.82, P < 0.001]. Similarly, results from logistic regression analysis demonstrated that individuals who had skin test indurations >= 10 mm were 6.82 times more likely than individuals who had skin test indurations < 10 mm to have high levels of IFN-gamma (i.e. positive QFTGIT result) (adjusted odd ratio = 6.82; 95% CI, 3.67 to 12.69, P < 0.001). In conclusion, the results of this study could provide indirect evidence for the prognostic use of the QFTGIT assay for progression of Mtb infection, though prospective follow-up studies are needed to provide direct evidence. PMID- 22298885 TI - Predicting and preventing cardiovascular disease in HIV-infected patients. AB - Cardiovascular disease (CVD) is the leading cause of non-HIV-related death in HIV infected persons. The risk of CVD in HIV-infected persons appears to reflect the contribution of a number of factors, including non-HIV-related (traditional) cardiovascular risk factors, chronic inflammation associated with HIV infection, and metabolic adverse effects of antiretroviral therapy. Traditional CVD risk factors, however, are the major determinants of risk in HIV-infected patients and this population carries a high burden of such factors. HIV infection may also be an independent risk factor for CVD, but there is not yet sufficient evidence to consider HIV infection itself a coronary heart disease risk equivalent (eg, in the same manner as diabetes) or to change calculation of risk in the HIV-infected population. In the absence of specific randomized trials in the HIV-infected population, HIV-infected persons should be treated for cardiovascular risk factors according to current national guidelines for reducing risk, including those for aspirin use and for treatment of dyslipidemia, hypertension, and metabolic syndrome. This article summarizes a presentation by Wendy S. Post, MD, at the 14th Annual Clinical Conference for the Ryan White HIV/AIDS Program held in Tampa, Florida, in June 2011. Dr Kerunne Ketlogetswe provided additional editing. The Clinical Conference is sponsored by the IAS-USA under the Health Resources and Services Administration (HRSA) contract number HHSH250200900010C. PMID- 22298886 TI - Evaluating cognitive impairment in the clinical setting: practical screening and assessment tools. AB - HIV-associated neurocognitive disorders (HAND) remain a substantial problem in the era of combination antiretroviral therapy. Neither the Mini Mental State Exam nor the HIV Dementia Scale is sufficiently sensitive for HAND. The Montreal Cognitive Assessment shows promise, but current data suggest that adding an additional test will be needed to improve sensitivity for the clinical setting. Patient reporting of symptoms is insensitive as most cases of HAND are asymptomatic. Examination of cerebrospinal fluid (CSF) is sometimes warranted in select patients to evaluate for CSF HIV RNA detectability. CSF escape of virus, when CSF HIV RNA is detectable but plasma HIV RNA is not, appears to be a relatively uncommon event in the clinical setting where the level of detectability for typical clinical assays is around 50 copies/mL. In cases of CSF escape, cognitive improvement has been linked to changes in antiretroviral regimens that are aimed at either overcoming antiretroviral resistance or improving central nervous system (CNS) penetration-effectiveness. Currently, for most patients with HAND in the absence of unusual features, there are insufficient data for a recommendation to routinely intensify therapy with a neurointensive antiretroviral regimen; however, there is considerable uncertainty given emerging data and variability in approach among experts in the field. This article summarizes a case-based presentation by Victor G. Valcour, MD, at the 14th Annual Clinical Conference for the Ryan White HIV/AIDS Program held in Tampa, Florida, in June 2011. The Clinical Conference is sponsored by the IAS-USA under the Health Resources and Services Administration (HRSA) contract number HHSH250200900010C. PMID- 22298887 TI - HIV preexposure prophylaxis: new data and potential use. AB - HIV preexposure prophylaxis (PrEP) has demonstrated efficacy in 4 studies: 1) the CAPRISA 004 trial of pericoital administration of 1% tenofovir gel showed moderate (39%) efficacy in reducing risk of HIV acquisition in young women; 2) the iPrEx trial of daily oral emtricitabine/tenofovir had moderate (44%) efficacy in reducing risk of HIV acquisition among high-risk men who have sex with men (MSM); 3) the Partners PrEP Study in African HIV-serodiscordant couples, in which the HIV-seronegative partner received daily oral tenofovir or emtricitabine/tenofovir, showed high efficacy (62% and 73%, respectively); and 4) the TDF2 trial in young heterosexual men and women in Botswana demonstrated 62% efficacy of daily oral emtricitabine/tenofovir. Greater adherence to PrEP is associated with greater efficacy. Resistance to tenofovir and emtricitabine have been rare and were primarily observed during PrEP initiation in those with acute HIV infection. PrEP has been found to be safe and well tolerated. The FEM-PrEP trial of oral emtricitabine/tenofovir and the VOICE trials of daily 1% tenofovir gel and oral tenofovir (both studies conducted in African women) did not show protective benefit, for reasons that currently remain unknown. The Bangkok Tenofovir Study of oral tenofovir in injection drug users, and the emtricitabine/tenofovir study arm of the VOICE trial, are ongoing. Establishing PrEP programs will be a great challenge and a great opportunity. This article summarizes a presentation by Connie L. Celum, MD, MPH, at the IAS-USA live continuing education course held in Chicago in June 2011, and includes updates on PrEP trial results reported since July 2011. PMID- 22298888 TI - Update of the past year: a review from IDSA 2011. AB - The Infectious Diseases Society of America Annual Meeting serves as a time of expert review of the year's most important innovations. Important new information on HIV infection incidence was discussed. The remarkable efficacy of "treatment as prevention" in the HIV Prevention Trials Network (HPTN) 052 study and the proper place of oral preexposure prophylaxis were among the important prevention topics. Key engagement-in-care research indicates that only 19% of HIV-infected persons in the United States have a plasma HIV RNA level below the limits of assay detection. Among antiretroviral topics, the role of the newly approved nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine was discussed. Primary care topics for the HIV-infected population included treatment of triglyceride level elevations and bone health. The newly published data on the proper timing of antiretroviral therapy initiation after starting tuberculosis treatment were highlighted. Finally, exciting advances in the treatment of hepatitis C virus (HCV) infection necessitate that practitioners understand the complexities of treating HIV/HCV coinfections. PMID- 22298889 TI - Neoplastic cells are a rare component in human glioblastoma microvasculature. AB - Microvascular proliferation is a key biological and diagnostic hallmark of human glioblastoma, one of the most aggressive forms of human cancer. It has recently been suggested that stem-like glioblastoma cells have the capacity to differentiate into functional endothelial cells, and that a significant proportion of the vascular lining in tumors has a neoplastic origin. In principle, this finding could significantly impact the efficacy and development of antiangiogenic therapies targeting the vasculature. While the potential of stem-like cancer cells to form endothelium in culture seems clear, in our clinical experience using a variety of molecular markers, neoplastic cells do not contribute significantly to the endothelial-lined vasculature of primary human glioblastoma. We sought to confirm this impression by analyzing vessels in glioblastoma previously examined using chromogenic in situ hybridization (CISH) for EGFR and immunohistochemistry for mutant IDH1. Vessels containing cells expressing these definitive neoplastic markers were identified in a small fraction of tumors, but only 10% of vessel profiles examined contained such cells and when identified these cells comprised less than 10% of the vascular cellularity in the cross section. Interestingly, these rare intravascular cells showing EGFR amplification by CISH or mutant IDH1 protein by immunohistochemistry were located in the middle or outer portions of vessel walls, but not amongst the morphologic boundaries of the endothelial lining. To more directly address the capacity of glioblastoma cells to contribute to the vascular endothelium, we performed double labeling (Immunofluorescence/FISH) for the endothelial marker CD34 and EGFR gene locus. This analysis did not identify EGFR amplified CD34+ endothelial cells within vascular linings, and further supports our observation that incorporation of glioblastoma cells into the tumor vessels is, at best, extremely rare of questionable clinical or therapeutic significance. PMID- 22298891 TI - A millennium goal for cancer. PMID- 22298892 TI - Overview of the AACR Clinical and Translational Cancer Research Think Tank meeting. PMID- 22298893 TI - Impact of genomics on personalized cancer medicine. AB - Recent advances in tumor genetics and drug development have led to the generation of a wealth of anticancer targeted therapies. A few recent examples indicate that these drugs are mainly, if not exclusively, active against tumors of a particular genotype that can be identified by a diagnostic test, usually by detecting a somatic alteration in the tumor DNA. However, for the majority of targeted therapies in development, there are still no clinical tools to determine which patients are most likely to benefit or, alternatively, be resistant de novo to these novel agents or drug combinations. PMID- 22298894 TI - Making personalized cancer medicine a reality: challenges and opportunities in the development of biomarkers and companion diagnostics. AB - The origins of this article stem from discussions at the American Association for Cancer Research Clinical and Translational Cancer Research Think Tank meeting held in San Francisco in early 2010. This article synthesizes the opinions and issues considered at that meeting, and discusses many of the important events that have since occurred in the field of personalized cancer medicine. Although investigators continue to make progress in better linking individual patient biology with risk determination, diagnosis, prognosis, and treatment selection, the pace of this progress continues to be limited by many of the issues identified in the meeting. PMID- 22298895 TI - Genetically modified mouse models for biomarker discovery and preclinical drug testing. AB - The ability to grow pluripotent mouse embryonic stem cells in culture, and to introduce precise genetic modifications into those cells through gene targeting, has greatly facilitated the generation of mouse models of human disease. This technology is playing a particularly important role in cancer research. In addition to their use in elucidating the role of individual genes or combinations of 2 or more genes, the genetically engineered mouse models are being used to develop biomarkers and for preclinical drug testing. By examining plasma samples from tumor-bearing mice from mice carrying specific mutations in tumor suppressor genes and/or oncogenes, investigators can identify tumor-specific biomarkers that are overexpressed in the tumor cells. These markers are directly relevant to the corresponding human cancer. The ability to generate tumors at the correct anatomical site within the normal cellular environment is augmenting the use of xenografts in drug testing in a preclinical setting. PMID- 22298896 TI - Imaging: strategies, controversies, and opportunities. AB - At a Clinical and Translational Cancer Research Think Tank meeting sponsored by the American Association for Cancer Research in 2010, one of the breakout groups focused on new technologies and imaging. The discussions emphasized new opportunities in translational imaging and its role in the future, rather than established techniques that are currently in clinical practice. New imaging methods under development are changing the approach of imaging science from a focus on the anatomic description of disease to a focus on the molecular basis of disease. Broadly referred to as molecular imaging, these new strategies directly embrace the incorporation of cell and molecular biology concepts and techniques into image generation and can involve the introduction of genes into cells with the explicit intent to image the end products of gene expression with external imaging devices. These new methods hold the promise of providing clinicians with (i) robust linkages between cell and animal models and clinical trials, (ii) in vivo biomarkers that can be measured repeatedly and sequentially over time to observe dynamic disease processes and responses to treatment, and (iii) tools for preselection and patient population enrichment in phase II and III trials to improve outcomes and better direct treatment. These strategies provide real-time pharmacodynamic parameters and can be powerful tools to monitor therapeutic effects in a spatially and tissue-specific manner, which may reduce cost during drug development, because pharmacodynamic studies in animals can inform clinical trials and accelerate the translation process. The Imaging Response Assessment Team (IRAT) program serves as an example of how imaging techniques can be incorporated into clinical trials. IRATs work to advance the role of imaging in assessment of response to therapy and to increase the application of quantitative anatomic, functional, and molecular imaging endpoints in clinical trials, and imaging strategies that will lead to individualized patient care. PMID- 22298897 TI - Reports from the 2010 Clinical and Translational Cancer Research Think Tank meeting: design strategies for personalized therapy trials. AB - It has long been evident that cancer is a heterogeneous disease, but only relatively recently have we come to realize the extent of this heterogeneity. No single therapy is effective for every patient with tumors having the same histology. A clinical strategy based on a single-therapy approach results in overtreatment for the majority of patients. Biomarkers can be considered as knives that dissect the disease ever more finely. The future of clinical research will be based on learning whether certain therapies are more appropriate than others for biomarker-defined subsets of patients. Therapies will eventually be tailored to narrow biomarker subsets. The ability to determine which therapies are appropriate for which patients requires information from biological science as well as empirical evidence from clinical trials. Neither is easy to achieve. Here we describe some nascent approaches for designing clinical trials that are biomarker-based and adaptive. Our focus is on adaptive trials that address many questions at once. In a way, these clinical experiments are themselves part of a much larger experiment: learning how (or whether it is possible) to design experiments that match patients in small subsets of disease with therapies that are especially effective and possibly even curative for them. PMID- 22298899 TI - The Journal of Physiology Annual Report 2011-12. PMID- 22298898 TI - Activation of beta-catenin signaling in androgen receptor-negative prostate cancer cells. AB - PURPOSE: To study Wnt/beta-catenin in castrate-resistant prostate cancer (CRPC) and understand its function independently of the beta-catenin-androgen receptor (AR) interaction. EXPERIMENTAL DESIGN: We carried out beta-catenin immunocytochemical analysis, evaluated TOP-flash reporter activity (a reporter of beta-catenin-mediated transcription), and sequenced the beta-catenin gene in MDA prostate cancer 118a, MDA prostate cancer 118b, MDA prostate cancer 2b, and PC-3 prostate cancer cells. We knocked down beta-catenin in AR-negative MDA prostate cancer 118b cells and carried out comparative gene-array analysis. We also immunohistochemically analyzed beta-catenin and AR in 27 bone metastases of human CRPCs. RESULTS: beta-Catenin nuclear accumulation and TOP-flash reporter activity were high in MDA prostate cancer 118b but not in MDA prostate cancer 2b or PC-3 cells. MDA prostate cancer 118a and MDA prostate cancer 118b cells carry a mutated beta-catenin at codon 32 (D32G). Ten genes were expressed differently (false discovery rate, 0.05) in MDA prostate cancer 118b cells with downregulated beta-catenin. One such gene, hyaluronan synthase 2 (HAS2), synthesizes hyaluronan, a core component of the extracellular matrix. We confirmed HAS2 upregulation in PC-3 cells transfected with D32G-mutant beta-catenin. Finally, we found nuclear localization of beta-catenin in 10 of 27 human tissue specimens; this localization was inversely associated with AR expression (P = 0.056, Fisher's exact test), suggesting that reduced AR expression enables Wnt/beta catenin signaling. CONCLUSION: We identified a previously unknown downstream target of beta-catenin, HAS2, in prostate cancer, and found that high beta catenin nuclear localization and low or no AR expression may define a subpopulation of men with bone metastatic prostate cancer. These findings may guide physicians in managing these patients. PMID- 22298900 TI - Reactive oxygen species enter the tug-of-war between metabolic vasodilatation and sympathetic vasoconstriction. PMID- 22298901 TI - Epithelial biology in the gastrointestinal system: insights into normal physiology and disease pathogenesis. PMID- 22298902 TI - Extracting autonomic information from oscillations in MSNA. PMID- 22298904 TI - Aberrant chondrocyte hypertrophy and activation of beta-catenin signaling precede joint ankylosis in ank/ank mice. AB - OBJECTIVE: We assessed the role of Ank in the maintenance of postnatal articular cartilage using the ank/ank mouse (mice homozygous for progressive ankylosis). METHODS: We analyzed ank/ank mice and wild-type littermates (8, 12, and 18 weeks old). Sections from decalcified, paraffin-embedded joints were stained with hematoxylin and eosin. Articular chondrocyte size and cartilage thickness were determined using morphometric methods. Immuno-histochemical staining was performed with anticollagen X, antitissue nonspecific alkaline phosphatase (TNAP), and anti-beta-catenin antibodies on fixed joint sections. Axin2 expression in paw joint lysates in wild-type versus ank/ank mice were compared using Western blot analysis. RESULTS: In all age groups of normal mice studied, calcified cartilage (CC) chondrocyte areas were significantly larger than those of uncalcified cartilage (UC) chondrocytes. However, similar chondrocyte areas (UC vs CC) were found in 12-week and 18-week-old ank/ank mice, indicating that hypertrophic chondrocytes were present in the UC of these mutant mice. The ank/ank mice showed an increase in CC thickness. The ank/ank UC hypertrophic chondrocytes showed diffuse immuno-reactivity for collagen X and TNAP. Increased beta-catenin activation was demonstrated by nuclear localization of beta-catenin staining in ank/ank chondrocytes. Axin2 expression from paw lysates was downregulated in ank/ank mice. CONCLUSION: We identified a previously unrecognized phenotype in the articular cartilage of ank/ank mice: collagen X positive hypertrophic chondrocytes in the UC. It is possible that consequent to downregulation of axin2 expression, beta-catenin signaling was activated, leading to accelerated chondrocyte maturation and eventual ankylosis in ank/ank joints. Our studies shed new light on the contribution of a key signaling pathway in this model of joint ankylosis. PMID- 22298905 TI - Parent and child acceptable symptom state in juvenile idiopathic arthritis. AB - OBJECTIVE: To explore the parent and child acceptable symptom state in juvenile arthritis (JA-PASS and JA-CASS, respectively) and estimate the JA-PASS and JA CASS cutoff values for outcome measures. METHODS: Children with juvenile idiopathic arthritis (JIA) and their parents completed a multi-dimensional questionnaire that included parent-reported and child-reported outcomes and a question about whether they considered the disease state as satisfactory. Additional assessments included demographic data, physician-reported outcomes, and acute-phase reactant levels. Stepwise logistic regression was used to assess contributors to JA-PASS and JA-CASS. Cutoff values of outcome measures that defined JA-PASS and JA-CASS were determined using both 75th percentile and receiver-operating characteristic (ROC) curve methods. Testing procedures included evaluation of discriminative and construct validity of the satisfaction question and assessment of reliability of JA-PASS and JA-PASS cutoffs. RESULTS: Of 584 parents, 385 (65.9%) considered their child in JA-PASS. Of 343 children, 236 (68.8%) considered themselves in JA-CASS. Significant contributors to being in either JA-PASS or JA-CASS were absence of active joints, better rating of overall well-being, and better physical function or health. Cutoff values yielded by 75th percentile and ROC curve methods were similar. Parent, child, and physician global ratings yielded the lowest percentage of false-positive misclassification and the best tradeoff between sensitivity and specificity. The satisfaction question showed good discriminative and construct validity and the JA-PASS and JA-PASS cutoffs were found to be stable over time. CONCLUSION: The acceptable symptom state is a relevant concept for children with JIA and their parents and constitutes a valid outcome measure that is potentially applicable in routine practice and clinical trials. PMID- 22298906 TI - Dysregulation of the microvasculature in nonlesional non-sun-exposed skin of patients with lupus nephritis. AB - OBJECTIVE: Membrane endothelial protein C receptor (mEPCR) is highly expressed in peritubular capillaries of kidneys from patients with active and poorly responsive lupus nephritis (LN). We investigated the hypothesis that changes in the microvasculature are widespread with extension to the dermal vasculature. METHODS: Skin biopsies from uninvolved skin (buttocks) were performed in 27 patients with LN and 5 healthy controls. Sections were stained with specific antibodies reactive with mEPCR, adiponectin, intercellular adhesion molecule-1 (ICAM-1), and CD31; then assessed by enumeration of stained blood vessels (percentage positive blood vessels) blinded to knowledge of clinical information. RESULTS: There was a significant increase in the prevalence of blood vessels that stained for mEPCR and ICAM-1 in patients compared to controls [94% vs 59% (p = 0.045) and 81% vs 67% (p = 0.037), respectively]. Adiponectin staining and CD31 staining were similar between the groups (45% vs 43% and 98% vs 92%). Dermal staining for mEPCR was greater in patients with proliferative glomerulonephritis than in those with membranous disease (96% vs 60%; p = 0.029). A composite of poor prognostic renal markers and death was significantly associated with greater expression of mEPCR staining. CONCLUSION: These data are consistent with the notion that in patients with LN, activation of the microvasculature extends beyond the clinically targeted organ. The insidious expression of this widespread vasculopathy may be a contributor to longterm comorbidities. PMID- 22298907 TI - Magnetic resonance imaging and radiographic assessment of carpal depressions in children with juvenile idiopathic arthritis: normal variants or erosions? AB - OBJECTIVE: Magnetic resonance imaging (MRI) is playing an increasingly important role in the diagnosis and followup of juvenile idiopathic arthritis (JIA). Carpal depressions are commonly observed in healthy children and in patients with JIA. The aim of our study was to further characterize these depressions in patients with JIA. METHODS: A total of 29 MRI wrist examinations were analyzed. Depressions were classified according to morphology as either tubular or focal. Features including the presence of a vessel related to the depression, evidence of synovitis, bone marrow edema, or loss of joint space on a radiograph taken on the same day were recorded for each depression. RESULTS: A total of 173 depressions were identified in 145 carpal bones. Forty percent were capitate depressions. A third were focal depressions and two-thirds were tubular. About 10% of tubular depressions and 30% of focal depressions were associated with features suggesting true erosions, with the remainder likely to represent vascular channels and normal variants. CONCLUSION: Radiologists and clinicians should undertake caution when assessing carpal depressions on MRI because the vast majority are likely to represent normal variants. PMID- 22298908 TI - Construct and criterion validity of the short form-6D utility measure in patients with systemic lupus erythematosus. AB - OBJECTIVE: Preference-based measures, such as the Short Form-6D (SF-6D), allow quality-adjusted life-years, used in cost-utility evaluations, to be calculated. We investigated the construct and criterion validity of the SF-6D in patients with systemic lupus erythematosus (SLE). METHODS: Female patients with SLE were recruited from outpatient clinics at 2 timepoints, 5 years apart. Cross-sectional correlation of the SF-6D with domains of the disease-specific LupusQol health related quality of life (HRQOL) measure, the Systemic Lupus International Collaborating Clinics Damage Index (SDI; for damage) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; for activity) measures, and patient characteristics was tested. The ability to discriminate between groups defined by smoking status, presence/absence of carotid plaque, depression, and fatigue was tested using the t-test. RESULTS: In total 181 patients were recruited at baseline. The SF-6D correlated moderately to strongly with all domains of the LupusQoL (0.6-0.8) apart from intimate relationships (0.42) and body image (0.34). Correlations of the SF-6D with the demographic and disease-specific measures at baseline were small for the SDI score (-0.23) and age (-0.19) and in the expected direction. The SF-6D did not correlate with disease activity (SLEDAI -0.08). The SF-6D could distinguish those who smoked, had carotid plaque, had depression, and reported fatigue from those who did not, with the largest effect size being for depression (0.75). CONCLUSION: The SF-6D displays construct and criterion validity for use in patients with SLE, but the low correlation with aspects of intimate relationships and body image represents a concern and reinforces the need to collect disease-specific measures of HRQOL alongside generic preference-based instruments. PMID- 22298909 TI - Cycle decompositions: From graphs to continua. AB - We generalise a fundamental graph-theoretical fact, stating that every element of the cycle space of a graph is a sum of edge-disjoint cycles, to arbitrary continua. To achieve this we replace graph cycles by topological circles, and replace the cycle space of a graph by a new homology group for continua which is a quotient of the first singular homology group [Formula: see text]. This homology seems to be particularly apt for studying spaces with infinitely generated [Formula: see text], e.g. infinite graphs or fractals. PMID- 22298910 TI - Reciprocity of agonistic support in ravens. AB - Cooperative behaviour through reciprocation or interchange of valuable services in primates has received considerable attention, especially regarding the timeframe of reciprocation and its ensuing cognitive implications. Much less, however, is known about reciprocity in other animals, particularly birds. We investigated patterns of agonistic support (defined as a third party intervening in an ongoing conflict to attack one of the conflict participants, thus supporting the other) in a group of 13 captive ravens, Corvus corax. We found support for long-term, but not short-term, reciprocation of agonistic support. Ravens were more likely to support individuals who preened them, kin and dominant group members. These results suggest that ravens do not reciprocate on a calculated tit-for-tat basis, but aid individuals from whom reciprocated support would be most useful and those with whom they share a good relationship. Additionally, dyadic levels of agonistic support and consolation (postconflict affiliation from a bystander to the victim) correlated strongly with each other, but we found no evidence to suggest that receiving agonistic support influences the victim's likelihood of receiving support (consolation) after the conflict ends. Our findings are consistent with an emotionally mediated form of reciprocity in ravens and provide additional support for convergent cognitive evolution in birds and mammals. PMID- 22298911 TI - Hydration of highly charged ions. AB - Based on a series of ab initio quantum mechanical charge field molecular dynamics (QMCF MD) simulations, the broad spectrum of structural and dynamical properties of hydrates of trivalent and tetravalent ions is presented, ranging from extreme inertness to immediate hydrolysis. Main group and transition metal ions representative for different parts of the periodic system are treated, as are 2 threefold negatively charged anions. The results show that simple predictions of the properties of the hydrates appear impossible and that an accurate quantum mechanical simulation in cooperation with sophisticated experimental investigations seems the only way to obtain conclusive results. PMID- 22298912 TI - Blends of canal surfaces from polyhedral medial transform representations. AB - We present a new method for constructing [Formula: see text] blending surfaces between an arbitrary number of canal surfaces. The topological relation of the canal surfaces is specified via a convex polyhedron and the design technique is based on a generalization of the medial surface transform. The resulting blend surface consists of trimmed envelopes of one- and two-parameter families of spheres. Blending the medial surface transform instead of the surface itself is shown to be a powerful and elegant approach for blend surface generation. The performance of our approach is demonstrated by several examples. PMID- 22298913 TI - Axisymmetric indentation of curved elastic membranes by a convex rigid indenter. AB - Motivated by applications to seed germination, we consider the transverse deflection that results from the axisymmetric indentation of an elastic membrane by a rigid body. The elastic membrane is fixed around its boundary, with or without an initial pre-stretch, and may be initially curved prior to indentation. General indenter shapes are considered, and the load-indentation curves that result for a range of spheroidal tips are obtained for both flat and curved membranes. Wrinkling may occur when the membrane is initially curved, and a relaxed strain-energy function is used to calculate the deformed profile in this case. Applications to experiments designed to measure the mechanical properties of seed endosperms are discussed. PMID- 22298914 TI - Hermit crabs and their symbionts: Reactions to artificially induced anoxia on a sublittoral sediment bottom. AB - Hermit crabs play an important role in the Northern Adriatic Sea due to their abundance, wide range of symbionts, and function in structuring the benthic community. Small-scale (0.25 m(2)) hypoxia and anoxia were experimentally generated on a sublittoral soft bottom in 24 m depth in the Gulf of Trieste. This approach successfully simulates the seasonal low dissolved oxygen (DO) events here and enabled studying the behaviour and mortality of the hermit crab Paguristes eremita. The crabs exhibited a sequence of predictable stress responses and ultimately mortality, which was correlated with five oxygen thresholds. Among the crustaceans, which are a sensitive group to oxygen depletion, P. eremita is relatively tolerant. Initially, at mild hypoxia (2.0 to 1.0 ml l(- 1) DO), hermit crabs showed avoidance by moving onto better oxygenated, elevated substrata. This was accompanied by a series of responses including decreased locomotory activity, increased body movements and extension from the shell. During a moribund phase at severe hypoxia (0.5 to 0.01 ml l(- 1) DO), crabs were mostly immobile in overturned shells and body movements decreased. Anoxia triggered emergence from the shell, with a brief locomotion spurt of shell-less crabs. The activity pattern of normally day-active crabs was altered during hypoxia and anoxia. Atypical interspecific interactions occurred: the crab Pisidia longimana increasingly aggregated on hermit crab shells, and a hermit crab used the emerged infaunal sea urchin Schizaster canaliferus as an elevated substrate. Response patterns varied somewhat according to shell size or symbiont type (the sponge Suberites domuncula). Mortality occurred after extended anoxia (~ 1.5 d) and increased hydrogen sulphide levels (H(2)S ~ 128 MUmol). The relative tolerance of crabs and certain symbionts (e.g. the sea anemone Calliactis parasitica) - as potential survivors and recolonizers of affected areas - may influence and promote community recovery after oxygen crises. PMID- 22298915 TI - Investigation of model uncertainties in Bayesian structural model updating. AB - Model updating procedures are applied in order to improve the matching between experimental data and corresponding model output. The updated, i.e. improved, finite element (FE) model can be used for more reliable predictions of the structural performance in the target mechanical environment. The discrepancies between the output of the FE-model and the results of tests are due to the uncertainties that are involved in the modeling process. These uncertainties concern the structural parameters, measurement errors, the incompleteness of the test data and also the FE-model itself. The latter type of uncertainties is often referred to as model uncertainties and is caused by simplifications of the real structure that are made in order to reduce the complexity of reality. Several approaches have been proposed for taking model uncertainties into consideration, where the focus of this manuscript will be set on the updating procedure within the Bayesian statistical framework. A numerical example involving different degrees of nonlinearity will be used for demonstrating how this type of uncertainty is considered within the Bayesian updating procedure. PMID- 22298916 TI - Multi-scale 2D tracking of articulated objects using hierarchical spring systems. AB - This paper presents a flexible framework to build a target-specific, part-based representation for arbitrary articulated or rigid objects. The aim is to successfully track the target object in 2D, through multiple scales and occlusions. This is realized by employing a hierarchical, iterative optimization process on the proposed representation of structure and appearance. Therefore, each rigid part of an object is described by a hierarchical spring system represented by an attributed graph pyramid. Hierarchical spring systems encode the spatial relationships of the features (attributes of the graph pyramid) describing the parts and enforce them by spring-like behavior during tracking. Articulation points connecting the parts of the object allow to transfer position information from reliable to ambiguous parts. Tracking is done in an iterative process by combining the hypotheses of simple trackers with the hypotheses extracted from the hierarchical spring systems. PMID- 22298917 TI - Public Health Reports. A message from the editor. PMID- 22298918 TI - Medication adherence: helping patients take their medicines as directed. PMID- 22298919 TI - A review of antibiotic use in food animals: perspective, policy, and potential. AB - Antibiotic use plays a major role in the emerging public health crisis of antibiotic resistance. Although the majority of antibiotic use occurs in agricultural settings, relatively little attention has been paid to how antibiotic use in farm animals contributes to the overall problem of antibiotic resistance. The aim of this review is to summarize literature on the role of antibiotics in the development of resistance and its risk to human health. We searched multiple databases to identify major lines of argument supporting the role of agricultural antibiotic use in the development of resistance and to summarize existing regulatory and policy documents. Several lines of reasoning support the conclusion that agricultural antibiotics are associated with resistance, yet most public policy is based on expert opinion and consensus. Finally, we propose strategies to address current gaps in knowledge. PMID- 22298921 TI - Chlamydia positivity in women screened in family planning clinics: racial/ethnic differences and trends in the northwest U.S., 1997-2006. AB - OBJECTIVES: We assessed chlamydia trends, individual-level risk factors, and population-level area-based socioeconomic measures (ABSMs) associated with chlamydia infection in women attending U.S. Public Health Service (PHS) Region X Infertility Prevention Project (IPP) family planning (FP) clinics from 1997-2006. We then explored these measures within racial/ethnic subpopulations. METHODS: Using data from 667,223 chlamydia tests obtained from women aged 15-24 years screened in 201 FP clinics, we employed a generalized mixed model with logistic link, incorporating clinic and ZIP code as random effects to adjust for risk of chlamydia associated with individual- and population-level (areal) measures for the overall population and for each racial/ethnic subpopulation. RESULTS: Significant racial/ethnic differences in chlamydia persisted after adjusting for individual and aggregate factors. Relatively steep chlamydia gradients were found across racial/ethnic ABSM levels. Compared with white women, infection risk was significantly higher for black (adjusted odds ratio [AOR] = 1.93), American Indian/Alaska Native (AOR=1.62), Asian/Pacific Islander (AOR=1.42), and Hispanic (AOR=1.28) women. The impact of population-level ABSMs on chlamydia varied across racial/ethnic groups and was generally modest. Among white women, there was a significant 4% relative annual increase in predicted chlamydia during the 10-year period 1997-2006. Chlamydia positivity over time did not change for racial/ethnic minority groups after adjusting for individual- and population-level factors. CONCLUSIONS: Racial/ethnic differences in chlamydia persisted over time and were not mitigated by adjustment for aggregate socioeconomic position or areal racial/ethnic measures. Changes in project strategies will be needed to address racial/ethnic disparities for chlamydial infection among young female FP clinic clients. PMID- 22298920 TI - Trends in the risk of U.S. polio outbreaks and poliovirus vaccine availability for response. AB - OBJECTIVES: The United States eliminated indigenous wild polioviruses (WPVs) in 1979 and switched to inactivated poliovirus vaccine in 2000, which quickly ended all indigenous live poliovirus transmission. Continued WPV circulation and use of oral poliovirus vaccine globally allow for the possibility of reintroduction of these viruses. We evaluated the risk of a U.S. polio outbreak and explored potential vaccine needs for outbreak response. METHODS: We synthesized information available on vaccine coverage, exemptor populations, and population immunity. We used an infection transmission model to explore the potential dynamics of a U.S. polio outbreak and potential vaccine needs for outbreak response, and assessed the impacts of heterogeneity in population immunity for two different subpopulations with potentially low coverage. RESULTS: Although the risk of poliovirus introduction remains real, widespread transmission of polioviruses appears unlikely in the U.S., given high routine coverage. However, clusters of un- or underimmunized children might create pockets of susceptibility that could potentially lead to one or more paralytic polio cases. We found that the shift toward combination vaccine utilization, with limited age indications for use, and other current trends (e.g., decreasing proportion of the population with immunity induced by live polioviruses and aging of vaccine exemptor populations) might increase the vulnerability to poliovirus reintroduction at the same time that the ability to respond may decrease. CONCLUSIONS: The U.S. poliovirus vaccine stockpile remains an important resource that may potentially be needed in the future to respond to an outbreak if a live poliovirus gets imported into a subpopulation with low vaccination coverage. PMID- 22298922 TI - Racial/ethnic variations in the prevalence of selected major birth defects, metropolitan Atlanta, 1994-2005. AB - OBJECTIVES: Birth defects are the leading cause of infant mortality and are responsible for substantial child and adult morbidity. Documenting the variation in prevalence of birth defects among racial/ethnic subpopulations is critical for assessing possible variations in diagnosis, case ascertainment, or risk factors among such groups. METHODS: We used data from the Metropolitan Atlanta Congenital Defects Program, a population-based birth defects registry with active case ascertainment. We estimated the racial/ethnic variation in prevalence of 46 selected major birth defects among live births, stillbirths, and pregnancy terminations at >20 weeks gestation among mothers residing in the five central counties of metropolitan Atlanta between 1994 and 2005, adjusting for infant sex, maternal age, gravidity, and socioeconomic status (SES). We also explored SES as a potential effect measure modifier. RESULTS: Compared with births to non Hispanic white women, births to non-Hispanic black women had a significantly higher prevalence of five birth defects and a significantly lower prevalence of 10 birth defects, while births to Hispanic women had a significantly higher prevalence of four birth defects and a significantly lower prevalence of six birth defects. The racial/ethnic disparities in the prevalence of some defects varied by SES, but no clear pattern emerged. CONCLUSIONS: Racial/ethnic disparities were suggested in 57% of included birth defects. Disparities in the prevalence of birth defects may result from different underlying genetic susceptibilities; exposure to risk factors; or variability in case diagnosis, ascertainment, or reporting among the subpopulations examined. Policies that improve early diagnosis of birth defects could reduce associated morbidity and mortality. PMID- 22298923 TI - Michigan Clostridium difficile hospital discharges: frequency, mortality, and charges, 2002-2008. AB - OBJECTIVE: Clostridium difficile (C. difficile) causes an intestinal bacterial infection of increasing importance in Michigan residents and health-care facilities. The specific burden and health-care costs of C. difficile infection (CDI) were previously unknown. We evaluated the frequency, mortality, and health care charges of CDI from Michigan hospital discharge data. METHODS: The Michigan Department of Community Health purchased discharge data from all Michigan acute care hospitals from the Michigan Health and Hospital Association. We extracted all hospital discharges from 2002 through 2008 containing the International Classification of Diseases, Ninth Revision code for intestinal infection due to C. difficile. Discharges were stratified by principle diagnosis and comorbidity level. Total hospitalization charges were standardized to the 2008 U.S. dollar. RESULTS: From 2002 through 2008, 68,686 hospital discharges with CDI occurred. The annual rate increased from 463.1 to 1096.5 CDI discharges per 100,000 discharges. CDI discharge rates were substantially higher among the elderly, females, and black people. Of all CDI discharges, 5,924 (8.6%) patients died. The mean total health-care charge for the time period was $67,149, and the annual mean increased 35% from 2002 to 2008. Hospital charges varied significantly by race/ethnicity and age. People with Medicaid insurance accrued the highest charges. CONCLUSION: Across Michigan, the CDI burden is growing substantially and affecting vulnerable populations. Surveillance utilizing hospital discharge data can illuminate trends and inform intervention targets. To reduce disease and health-care charges, increased prevention and infection-control efforts should be directed toward high-risk populations, such as the elderly. PMID- 22298924 TI - Atrazine exposure in public drinking water and preterm birth. AB - OBJECTIVES: Approximately 13% of all births occur prior to 37 weeks gestation in the U.S. Some established risk factors exist for preterm birth, but the etiology remains largely unknown. Recent studies have suggested an association with environmental exposures. We examined the relationship between preterm birth and exposure to a commonly used herbicide, atrazine, in drinking water. METHODS: We reviewed Kentucky birth certificate data for 2004-2006 to collect duration of pregnancy and other individual-level covariates. We assessed existing data sources for atrazine levels in public drinking water for the years 2000-2008, classifying maternal county of residence into three atrazine exposure groups. We used logistic regression to analyze the relationship between atrazine exposure and preterm birth, controlling for maternal age, race/ethnicity, education, smoking, and prenatal care. RESULTS: An increase in the odds of preterm birth was found for women residing in the counties included in the highest atrazine exposure group compared with women residing in counties in the lowest exposure group, while controlling for covariates. Analyses using the three exposure assessment approaches produced odds ratios ranging from 1.20 (95% confidence interval [CI] 1.14, 1.27) to 1.26 (95% CI 1.19, 1.32), for the highest compared with the lowest exposure group. CONCLUSIONS: Suboptimal characterization of environmental exposure and variables of interest limited the analytical options of this study. Still, our findings suggest a positive association between atrazine and preterm birth, and illustrate the need for an improved assessment of environmental exposures to accurately address this important public health issue. PMID- 22298925 TI - Exposure to secondhand smoke at home and at work in California. AB - OBJECTIVES: We estimated self-reported secondhand smoke (SHS) exposure in California at home and at work. METHODS: We used data from the 2005 and 2007 California Health Interview Surveys (n=109,809) for home exposure analysis, and we used data from the 2002 and 2005 California Tobacco Surveys (n=12,883) for workplace exposure analysis. Differences in exposure by age, race/ethnicity, and socioeconomic characteristics were assessed using Chi-square tests and multivariate logistic regression analyses. RESULTS: In the home, children had the lowest rates of SHS exposure (3.4%), followed by adolescents (4.7%) and adults (6.0%). For all age groups, Hispanic people had the lowest exposure to SHS at home, and black people of all ages had higher exposure rates than white people. In the workplace, 12.9% of Californians were exposed to SHS. Men had higher rates of exposure than women, and rates declined with age. Hispanic people had the highest rates of SHS exposure at work (19.5%), followed by Asian/Pacific Islanders (10.5%), black people (10.4%), and white people (9.7%). Workplace exposure rates were highest for people who worked in stores or warehouses, followed by plants or factories, restaurants or bars, and vehicles. CONCLUSIONS: Despite many years of tough tobacco-control policies in California, people continue to be exposed to SHS at home and in the workplace. The policies that are already in place, such as smoke-free workplace laws, need to be fully enforced. Interventions for reducing SHS exposure should be targeted to the groups with the greatest exposure rates, including Hispanic people, black people, young adults, and those who work in high-exposure settings. PMID- 22298926 TI - Resources that may matter: the impact of local health department expenditures on health status. AB - OBJECTIVES: This study examines the association between changes in local health department (LHD) expenditures, aggregated to the state level, and changes in state-level measures of health, from 1993 to 2005. The literature on the impact of LHD resources on health status has been limited by cross-sectional designs. With repeated surveys of LHDs, it is now possible to use longitudinal designs to explore the association between LHD inputs and outcomes. METHODS: This was a retrospective cohort study. We used a fixed-effects regression model to assess the association between LHD expenditures, aggregated to the state level, and seven separate health measures. We derived LHD expenditure data from the National Association of County and City Health Officials' surveys of LHDs in 1993, 1997, and 2005. We obtained secondary data on seven health measures--smoking and obesity prevalence, infectious disease morbidity, infant mortality, deaths due to cardiovascular disease and cancer, and overall premature death--through the America's Health Rankings(r) reports, 1990-2008. Usable data were available for 1,470 LHDs, representing 37 states. RESULTS: An increase in LHD expenditures, aggregated to the state level, was associated with a statistically significant decline in state-level infectious disease morbidity (t= -3.28, p=0.002) and in years of potential life lost (YPLL) (t= -2.73, p=0.008). For every $10 increase in aggregated LHD expenditures per capita, infectious disease morbidity decreased by 7.4%, and YPLL decreased by 1.5%. CONCLUSION: LHD resources are associated with improvements in preventable causes of morbidity and mortality. PMID- 22298927 TI - Global health matters. PMID- 22298928 TI - Community influences on antenatal and delivery care in Bangladesh, Egypt, and Rwanda. PMID- 22298929 TI - Local acts. PMID- 22298930 TI - Impact of a New York City Health Department initiative to expand HIV partner services outside STD clinics. PMID- 22298931 TI - Public health chronicles. PMID- 22298932 TI - Unlinked anonymous testing for HIV in developing countries: a new ethical consensus. PMID- 22298934 TI - Medicaid's free-choice-of-provider protections in a family planning context: Planned Parenthood Federation of Indiana v. Commissioner of the Indiana State Department of Health. PMID- 22298936 TI - Social justice, health, and human rights education: challenges and opportunities in schools of public health. PMID- 22298937 TI - Development of a radionovela to promote HPV vaccine awareness and knowledge among Latino parents. PMID- 22298938 TI - A Career in Manuscripts: Genres and Purposes of a Physician's Writing in Rome, 1600-1630. AB - Following the stellar career of papal physician Giulio Mancini, the article brings into focus learned doctors' uses of, and relationships with, manu- scripts. Manuscripts were the main outcome of their practice - as letters of consultation to patients and colleagues, as consilia of various kinds, including for use in courts of law, and also in the form of key professional tools such as casebooks. Clues found in Mancini's rich paper-trail shed light on material aspects of his professional writing and on the role that circulating knowledge in manuscript had in creating and sustaining medical networks. The article also argues that even in a domain as shaped by print as early modern medicine, physicians' use of this medium should not be taken for granted; especially in courtly settings, scribal, as opposed to print, publishing provided them with an effective means of building the social relationships on which their careers depended. PMID- 22298939 TI - Interaction mining and skill-dependent recommendations for multi-objective team composition. AB - Web-based collaboration and virtual environments supported by various Web 2.0 concepts enable the application of numerous monitoring, mining and analysis tools to study human interactions and team formation processes. The composition of an effective team requires a balance between adequate skill fulfillment and sufficient team connectivity. The underlying interaction structure reflects social behavior and relations of individuals and determines to a large degree how well people can be expected to collaborate. In this paper we address an extended team formation problem that does not only require direct interactions to determine team connectivity but additionally uses implicit recommendations of collaboration partners to support even sparsely connected networks. We provide two heuristics based on Genetic Algorithms and Simulated Annealing for discovering efficient team configurations that yield the best trade-off between skill coverage and team connectivity. Our self-adjusting mechanism aims to discover the best combination of direct interactions and recommendations when deriving connectivity. We evaluate our approach based on multiple configurations of a simulated collaboration network that features close resemblance to real world expert networks. We demonstrate that our algorithm successfully identifies efficient team configurations even when removing up to 40% of experts from various social network configurations. PMID- 22298940 TI - Exploratory analysis of verbal aggression in romantic relationships among unmarried men and women: Predictive patterns by gender and race. AB - This is an exploratory study that examined verbal aggression in romantic relationships among unmarried Black and White women and men as a function of gender and race. We employed an ecological approach to examine the receipt of verbal aggression separately for men and women at the levels of individual, relationship, and community. We also explored whether gender-specific correlates of verbal aggression interacted with race. Analyses were based on a sample of 212 women and 133 men in non-marital romantic relationships recruited from 21 U.S. cities for a larger study. Linear mixed-effects models revealed that factors related to experiencing verbal aggression differed substantially for unmarried women and men in romantic relationships. Interesting racial differences also emerged distinctly for women and men. PMID- 22298941 TI - Weak values of a quantum observable and the cross-Wigner distribution. AB - We study the weak values of a quantum observable from the point of view of the Wigner formalism. The main actor here is the cross-Wigner transform of two functions, which is in disguise the cross-ambiguity function familiar from radar theory and time-frequency analysis. It allows us to express weak values using a complex probability distribution. We suggest that our approach seems to confirm that the weak value of an observable is, as conjectured by several authors, due to the interference of two wavefunctions, one coming from the past, and the other from the future. PMID- 22298942 TI - Imagery Rescripting of Early Traumatic Memories in Social Phobia. AB - Negative self-images appear to play a role in the maintenance of social phobia and research suggests they are often linked to earlier memories of socially traumatic events. Imagery rescripting is a clinical intervention that aims to update such unpleasant or traumatic memories, and is increasingly being incorporated in cognitive behavioral therapy programs. In previous research, we have found that imagery rescripting was superior to a control condition in terms of its beneficial effects on negative beliefs, image and memory distress, fear of negative evaluation, and anxiety in social situations. In this article, we describe our imagery rescripting procedure. We consider the importance of updating negative imagery in social phobia, the theoretical basis for imagery rescripting, directions for future research, and how to conduct imagery rescripting, including potential problems and their solutions. PMID- 22298943 TI - Patient considerations in early management of Parkinson's disease: focus on extended-release pramipexole. AB - This article reviews the role of an extended-release formulation of pramipexole in the treatment of Parkinson's disease at an early stage. Pramipexole is a nonergot D(2)/D(3) synthetic aminobenzothiazole derivative that is effective as monotherapy in early disease and as an adjunct to levodopa in patients with motor fluctuations. Although levodopa is the current "gold standard" for treatment of Parkinson's disease, its effectiveness fades rapidly and its use results in serious motor fluctuations (on-off, wearing-off, freezing, involuntary movements) for most patients with the disease. Pramipexole has selective actions at dopamine receptors belonging to the D(2) subfamily, where it possesses full activity similar to dopamine itself. Its preferential affinity for the D(3) receptor subtype could contribute to its efficacy in the treatment of both the motor and psychiatric symptoms of Parkinson's disease. The best approach to medical management of early Parkinson's disease remains controversial. While enormous progress has been made in the treatment of the disease, challenges still remain. A variety of treatment-related and patient-related factors must be taken into account when making these decisions. The current approach to treatment of early Parkinson's disease depends in part on individual patient factors, including age, severity and nature of symptoms and their impact, presence of cognitive dysfunction, possible underlying behavioral factors predisposing to impulse control disorders, and other comorbidities. Today, the once-daily extended release formulation of pramipexole offers the advantages of easy continuous delivery of drug and convenience to patients, particularly early in the disease when monotherapy is the rule. Thus, a new "levodopa-sparing" paradigm for treating Parkinson's disease may now be possible, whereby patients are initially treated with pramipexole and levodopa is added only as necessary. PMID- 22298944 TI - Patient assessment of an electronic device for subcutaneous self-injection of interferon beta-1a for multiple sclerosis: an observational study in the UK and Ireland. AB - BACKGROUND: Injectable disease-modifying drugs (DMDs) reduce the number of relapses and delay disability progression in patients with relapsing-remitting multiple sclerosis (RRMS). Regular self-injection can be stressful and impeded by MS symptoms. Auto-injection devices can simplify self-injection, overcome injection-related issues, and increase treatment satisfaction. This study investigated patient responses to an electronic auto-injection device. METHODS: Patients with RRMS (n = 63), aged 18-65 years, naive to subcutaneous (sc) interferon (IFN) beta-1a therapy, were recruited to a Phase IV, observational, open-label, multicenter study (NCT01195870). Patients self-injected sc IFN beta 1a using the RebiSmartTM (Merck Serono S.A. - Geneva, Switzerland) electronic auto-injector for 12 weeks, including an initial titration period if recommended by the prescribing physician. In week 12, patients completed a questionnaire comprising of a visual analog scale (VAS) to rate how much they liked using the device, a four-point response question on ease of use ('very difficult', 'difficult', 'easy', or 'very easy'), and a list of ten device functions to rank, based upon their experiences. RESULTS: Six patients (9.5%) discontinued the study: one switched to manual injection; two discontinued all treatment; three changed therapy. In total, 59 out of 63 patients (93.7%) completed the VAS; 54 out of 59 (91.5%; 95% confidence interval: 81.3%-97.2%) 'liked' using the electronic auto-injector (score >=6), whereas 57 out of 59 (96.6%) rated the device overall as 'easy' or 'very easy' to use. Device features rated as most useful were the hidden needle (mean [standard deviation] score: 3.3 [3.01]; n = 56), confirmation sound (3.9 [2.45]), and multidose cartridge (4.6 [2.32]). The least useful functions were the dose history list (8.0 [2.57]) and dose history calendar (7.5 [2.30]). CONCLUSIONS: These findings suggest that the electronic auto-injector may be suitable for patients who are new to injectable DMD therapy. Devices that simplify the injection process may help to ensure that patients receive the full benefits of treatment. PMID- 22298945 TI - An evaluation of the impact of patient cost sharing for antihypertensive medications on adherence, medication and health care utilization, and expenditures. AB - OBJECTIVE: To assess the impact of patient cost-sharing for antihypertensive medications on the proportion of days covered (PDC) by antihypertensive medications, medical utilization, and health care expenditures among commercially insured individuals assigned to different risk categories. METHODS: Participants were identified from the Consolidated Health Cost Guidelines (CHCG) database (January 1, 2006-December 31, 2008) based on a diagnosis (index) claim for hypertension, continuous enrollment >=12 months pre- and post-index, and no prior claims for antihypertensive medications. Participants were assigned to: low-risk group (no comorbidities), high-risk group (1+ selected comorbidities), or very high-risk group (prior hospitalization for 1+ selected comorbidities). The relationship between patient cost sharing and PDC by antihypertensive medications was assessed using standard linear regression models, controlling for risk group membership, and various demographic and clinical factors. The relationship between PDC and health care service utilization was subsequently examined using negative binomial regression models. RESULTS: Of the 28,688 study patients, 66% were low risk. The multivariate regression model supported a relationship between patient cost sharing per 30-day fill and PDC in the following year. For every US$1.00 increase in cost sharing, PDC decreased by 1.1 days (P < 0.0001). Significant predictors of PDC included high risk, older age, gender, Charlson Comorbidity Index score, geography, and total post-index insurer- and patient paid costs. An increase in PDC was associated with a decrease in all-cause and hypertension-related inpatient, outpatient, and emergency room visits and medical, pharmacy, and total costs. CONCLUSIONS: The trend has been for managed care organizations and employers to require patients to bear a greater out-of pocket burden for health care resources consumed. This study illustrates the potential adverse effects of higher patient cost sharing among patients with hypertension stratified by different risk levels. A decrease in PDC was predictive of higher resource utilization and health care costs, which should be of interest to payers and employers alike. PMID- 22298946 TI - Lanreotide depot deep subcutaneous injection: a new method of delivery and its associated benefits. AB - Acromegaly is a rare disease characterized by excessive growth hormone secretion, usually from a pituitary tumor. Treatment options include surgery, medical therapy, and in some cases, radiation therapy. Current medical therapy consists of treatment with somatostatin analog medications or a growth hormone receptor antagonist. There are two somatostatin analogs currently in use, octreotide and lanreotide. Both are supplied in long-acting formulations and are of comparable biochemical efficacy. Lanreotide is supplied in a prefilled syringe and is injected into deep subcutaneous tissue. Studies have been conducted to assess the efficacy of self- or partner administration, and have demonstrated that injection of lanreotide can be accomplished reliably and safely outside a physician's office. For patients who have achieved biochemical control with lanreotide, the FDA has recently approved an extended dosing interval. Selected patients may be able to receive the medication less frequently with injections of 120 mg administered every 6 or 8 weeks. This review focuses on the use of lanreotide in the treatment of acromegaly, the safety and efficacy of the drug, and the benefits afforded to patients because of unique aspects of the delivery of lanreotide. PMID- 22298947 TI - The subjective well-being under neuroleptic scale - short version (SWN-K) and the SF-36 health survey as quality of life measures in patients with schizophrenia. AB - PURPOSE: The desired outcome in schizophrenia treatment has evolved from symptom management to maximization of quality of life and functional recovery. The aim of this study was to assess the relationship between a specific well-being measure, the Subjective Well-being under Neuroleptic Scale - short version (SWN-K), and the SF-36 Health Survey as a generic quality of life measure. PATIENTS AND METHODS: A multicenter, cross-sectional study was conducted with clinically stable outpatients diagnosed with schizophrenia. Spearman's rank correlation was used to assess the associations between the SWN-K total score, its five subscales, and the SF-36 domains. RESULTS: Ninety-seven patients were included in the study. The mean age was 35 years (standard deviation = 10) and 72% were male. All correlations among domains were positive and most were statistically significant. The bodily pain domain of the SF-36 presented the lower correlations with the SWN-K (rho range 0.10-0.25), whereas the other seven domains correlated significantly (rho range 0.49-0.60, all P < 0.001). The largest correlations were obtained between the SWN-K and the SF-36 domains of general health (rho = 0.53), mental health (rho = 0.60), and vitality (rho = 0.54). CONCLUSION: The positive but nevertheless moderate correlations observed between a specific well-being instrument and a generic quality of life scale supports the inclusion of diagnosis-specific tools for outcome assessment of patients with schizophrenia. PMID- 22298948 TI - Aripiprazole in the acute and maintenance phase of bipolar I disorder. AB - Bipolar affective disorder is a disabling illness with substantial morbidity and many management challenges. Traditional mood stabilizers such as lithium, valproate, and carbamazepine are often inadequate in controlling symptoms both during the acute and maintenance phase of treatment. Aripiprazole is a second generation antipsychotic with a unique mechanism of action. Evidence suggests that it is effective in acute manic and mixed states. There are limited data to suggest its efficacy as a maintenance agent. Future studies will be needed to better define the role of aripiprazole relative to other traditional pharmacologic agents. PMID- 22298949 TI - Clinical utility of adjunctive retigabine in partial onset seizures in adults. AB - In ~30% of epileptic patients, full seizure control is not possible, which is why the search for novel antiepileptic drugs continues. Retigabine exhibits a mechanism of action that is not shared by the available antiepileptic drugs. This antiepileptic enhances potassium currents via Kv7.2-7.3 channels, which very likely results from destabilization of a closed conformation or stabilization of the open conformation of the channels. Generally, the pharmacokinetics of retigabine are linear and the drug undergoes glucuronidation and acetylation. Results from clinical trials indicate that, in the form of an add-on therapy, retigabine proves an effective drug in refractory epileptic patients. The major adverse effects of the add-on treatment are dizziness, somnolence, and fatigue. This epileptic drug is also considered for other conditions - neuropathic pain, affective disorders, stroke, or even Alzheimer's disease. PMID- 22298950 TI - Randomized Phase III evaluation of the efficacy and safety of a novel glycopyrrolate oral solution for the management of chronic severe drooling in children with cerebral palsy or other neurologic conditions. AB - AIM: To evaluate the efficacy of glycopyrrolate oral solution (1 mg/5 mL) in managing problem drooling associated with cerebral palsy and other neurologic conditions. METHOD: Thirty-eight patients aged 3-23 years weighing at least 27 lb (12.2 kg) with severe drooling (clothing damp 5-7 days/week) were randomized to glycopyrrolate (n = 20), 0.02-0.1 mg/kg three times a day, or matching placebo (n = 18). Primary efficacy endpoint was responder rate, defined as percentage showing >=3-point change on the modified Teacher's Drooling Scale (mTDS). RESULTS: Responder rate was significantly higher for the glycopyrrolate (14/19; 73.7%) than for the placebo (3/17; 17.6%) group (P = 0.0011), with improvements starting 2 weeks after treatment initiation. Mean improvements in mTDS at week 8 were significantly greater in the glycopyrrolate than in the placebo group (3.94 +/- 1.95 vs 0.71 +/- 2.14 points; P < 0.0001). In addition, 84% of physicians and 100% of parents/caregivers regarded glycopyrrolate as worthwhile compared with 41% and 56%, respectively, for placebo (P <= 0.014). Most frequently reported treatment-emergent adverse events (glycopyrrolate vs placebo) were dry mouth, constipation, and vomiting. INTERPRETATION: Children aged 3-16 years with problem drooling due to neurologic conditions showed a significantly better response, as assessed by mTDS, to glycopyrrolate than to placebo. CLINICALTRIALS.GOV IDENTIFIER: NCT00425087. PMID- 22298951 TI - Safety and efficacy of glycopyrrolate oral solution for management of pathologic drooling in pediatric patients with cerebral palsy and other neurologic conditions. AB - BACKGROUND: The purpose of this study was to assess the safety and efficacy of oral glycopyrrolate solution 1 mg/5 mL for 24 weeks in pediatric patients with chronic moderate-to- severe drooling associated with cerebral palsy and other neurologic conditions. METHODS: In this multicenter, open-label, 24-week study, males and females aged 3-18 years weighing at least 27 lb received oral glycopyrrolate solution, starting at 0.02 mg/kg three times daily and titrated in increments of 0.02 mg/kg every 5-7 days for 4 weeks to an optimal maintenance dose or a maximum dose of 0.1 mg/kg, but not exceeding 3 mg three times daily. Safety was assessed by description and tabulation of all adverse events. The primary efficacy endpoint was response, defined as at least a three-point change from baseline to week 24 on the modified Teacher's Drooling Scale. RESULTS: Of 137 intent-to-treat participants, 10 (7.3%) received the maximum dose of 0.1 mg/kg three times daily; 122 (89%) had at least one treatment-emergent adverse event, 47% related to oral glycopyrrolate solution, with most being mild-to moderate in intensity. The most commonly reported treatment-emergent adverse events were constipation (20.4%), vomiting (17.5%), diarrhea (17.5%), pyrexia (14.6%), dry mouth (10.9%), flushing (10.9%), and nasal congestion (10.9%). Nineteen patients (13.9%) discontinued treatment due to an adverse event, but no adverse event was specifically associated with discontinuation. Two patients had clinically significant toxicity grade shifts, one each in platelet count and calcium concentration. No deaths occurred on treatment; deaths of three patients (multisystem organ failure, anoxic encephalopathy, and aspiration pneumonia) within 30 days of their last dose were not considered to be treatment-related. At 24 weeks, 52.3% (95% confidence interval 43.7-60.9) of patients were responders, with at least a three-point decrease in modified Teacher's Drooling Scale from baseline, with 83.5% of parents/caregivers and 85.8% of investigators rating oral glycopyrrolate solution as being worthwhile. CONCLUSION: Oral glycopyrrolate solution 1 mg/5 mL for chronic moderate-to-severe drooling associated with cerebral palsy or other neurologic conditions was well tolerated over 24 weeks by pediatric patients aged 3-18 years. PMID- 22298952 TI - Adaptive Gaussian Predictive Process Models for Large Spatial Datasets. AB - Large point referenced datasets occur frequently in the environmental and natural sciences. Use of Bayesian hierarchical spatial models for analyzing these datasets is undermined by onerous computational burdens associated with parameter estimation. Low-rank spatial process models attempt to resolve this problem by projecting spatial effects to a lower-dimensional subspace. This subspace is determined by a judicious choice of "knots" or locations that are fixed a priori. One such representation yields a class of predictive process models (e.g., Banerjee et al., 2008) for spatial and spatial-temporal data. Our contribution here expands upon predictive process models with fixed knots to models that accommodate stochastic modeling of the knots. We view the knots as emerging from a point pattern and investigate how such adaptive specifications can yield more flexible hierarchical frameworks that lead to automated knot selection and substantial computational benefits. PMID- 22298953 TI - An updated nomenclature for keratin-associated proteins (KAPs). AB - Most protein in hair and wool is of two broad types: keratin intermediate filament-forming proteins (commonly known as keratins) and keratin-associated proteins (KAPs). Keratin nomenclature was reviewed in 2006, but the KAP nomenclature has not been revised since 1993. Recently there has been an increase in the number of KAP genes (KRTAPs) identified in humans and other species, and increasingly reports of variation in these genes. We therefore propose that an updated naming system is needed to accommodate the complexity of the KAPs. It is proposed that the system is founded in the previous nomenclature, but with the abbreviation sp-KAPm-nL*x for KAP proteins and sp-KRTAPm-n(p/L)*x for KAP genes. In this system "sp" is a unique letter-based code for different species as described by the protein knowledge-based UniProt. "m" is a number identifying the gene or protein family, "n" is a constituent member of that family, "p" signifies a pseudogene if present, "L" if present signifies "like" and refers to a temporary "place-holder" until the family is confirmed and "x" signifies a genetic variant or allele. We support the use of non-italicised text for the proteins and italicised text for the genes. This nomenclature is not that different to the existing system, but it includes species information and also describes genetic variation if identified, and hence is more informative. For example, GenBank sequence JN091630 would historically have been named KRTAP7-1 for the gene and KAP7-1 for the protein, but with the proposed nomenclature would be SHEEP-KRTAP7-1*A and SHEEP-KAP7-1*A for the gene and protein respectively. This nomenclature will facilitate more efficient storage and retrieval of data and define a common language for the KAP proteins and genes from all mammalian species. PMID- 22298954 TI - Measurement of hepatic protein fractional synthetic rate with stable isotope labeling technique in thapsigargin stressed HepG2 cells. AB - Severe burn-induced liver damage and dysfunction is associated with endoplasmic reticulum (ER) stress. ER stress has been shown to regulate global protein synthesis. In the current study, we induced ER stress in vitro and estimated the effect of ER stress on hepatic protein synthesis. The aim was two-fold: (1) to establish an in vitro model to isotopically measure hepatic protein synthesis and (2) to evaluate protein fractional synthetic rate (FSR) in response to ER stress. Human hepatocellular carcinoma cells (HepG2) were cultured in medium supplemented with stable isotopes 1,2-(13)C(2)-glycine and L-[ring-(13)C(6)]phenylalanine. ER stress was induced by exposing the cells to 100 nM of thapsigargin (TG). Cell content was collected from day 0 to 14. Alterations in cytosolic calcium were measured by calcium imaging and ER stress markers were confirmed by Western blotting. The precursor and product enrichments were detected by GC-MS analysis for FSR calculation. We found that the hepatic protein FSR were 0.97 +/- 0.02 and 0.99 +/- 0.05%/hr calculated from 1,2-(13)C(2)-glycine and L-[ring (13)C(6)]phenylalanine, respectively. TG depleted ER calcium stores and induced ER stress by upregulating p-IRE-1 and Bip. FSR dramatically decreased to 0.68 +/- 0.03 and 0.60 +/- 0.06%/hr in the TG treatment group (p<0.05, vs. control). TG induced ER stress inhibited hepatic protein synthesis. The stable isotope tracer incorporation technique is a useful method for studying the effects of ER stress on hepatic protein synthesis. PMID- 22298956 TI - Activated beta-catenin forces N2A cell-derived neurons back to tumor-like neuroblasts and positively correlates with a risk for human neuroblastoma. AB - Neuroblastoma is an embryonic malignancy arising from neuroblasts. The mechanisms that regulate the origination of neuroblastoma are still not very clear. In this study, we revealed that 6-bromoindirubin 3'-oxime (BIO), a specific GSK-3beta inhibitor, promoted N2A cells-derived neurons to become tumor-like neuroblasts. Moreover, constitutively activated beta-catenin (S33Y) also promoted this process, whereas, silencing endogenous expression of beta-catenin abolished BIO induced effects. These results implicated the potential relationship between the Wnt/beta-catenin signaling and neuroblastoma formation. Indeed, we found that the amount of beta-catenin in nucleus, which indicated the activation of Wnt/beta catnin signaling, was accumulated in human neuroblastoma specimens and positively correlated with clinical risk of neuroblastoma. These results give us a new sight into the neuroblastoma initiation and progression, and provide a potential drug target for neuroblastoma treatment. PMID- 22298955 TI - TGF-beta and BMP signaling in osteoblast differentiation and bone formation. AB - Transforming growth factor-beta (TGF-beta)/bone morphogenic protein (BMP) signaling is involved in a vast majority of cellular processes and is fundamentally important throughout life. TGF-beta/BMPs have widely recognized roles in bone formation during mammalian development and exhibit versatile regulatory functions in the body. Signaling transduction by TGF-beta/BMPs is specifically through both canonical Smad-dependent pathways (TGF-beta/BMP ligands, receptors and Smads) and non-canonical Smad-independent signaling pathway (e.g. p38 mitogen-activated protein kinase pathway, MAPK). Following TGF beta/BMP induction, both the Smad and p38 MAPK pathways converge at the Runx2 gene to control mesenchymal precursor cell differentiation. The coordinated activity of Runx2 and TGF-beta/BMP-activated Smads is critical for formation of the skeleton. Recent advances in molecular and genetic studies using gene targeting in mice enable a better understanding of TGF-beta/BMP signaling in bone and in the signaling networks underlying osteoblast differentiation and bone formation. This review summarizes the recent advances in our understanding of TGF beta/BMP signaling in bone from studies of genetic mouse models and human diseases caused by the disruption of TGF-beta/BMP signaling. This review also highlights the different modes of cross-talk between TGF-beta/BMP signaling and the signaling pathways of MAPK, Wnt, Hedgehog, Notch, and FGF in osteoblast differentiation and bone formation. PMID- 22298957 TI - Diagnosing And Treating Co-Morbid Sleep Apnea In Neurological Disorders. PMID- 22298958 TI - Predictors of aggressive inflammatory bowel disease. AB - Inflammatory bowel disease comprises a group of conditions characterized by idiopathic inflammation of the gastrointestinal tract. The natural course of disease can range from an indolent course with prolonged periods of remission to aggressive, incapacitating disease. Predicting which patients are more susceptible to developing severe disease is important, especially when choosing therapeutic agents and treatment strategies. This paper reviews current evidence on the main demographic, clinical, endoscopic, histologic, serologic, and genetic markers that predict aggressive inflammatory bowel disease. In ulcerative colitis, we considered disease to be aggressive when patients had a high relapse rate, need for admission and/or surgery, development of colon cancer, or extraintestinal manifestations. We defined aggressive Crohn's disease as having a high relapse rate, development of penetrating disease, need for repeat surgery, or multiple admissions for flares. In Crohn's disease, involvement of the upper gastrointestinal tract and ileum, penetrating disease, early age at diagnosis, smoking, extensive ulceration of the mucosa, high titers of serum antibodies, and mutations of the NOD2 gene are markers of aggressive disease. In ulcerative colitis, patients with more extensive involvement of the colon (pancolitis) have more symptomatology and are at higher risk for needing a colectomy and developing colon cancer. Also, plasmocytic infiltration of the colonic mucosa and crypt atrophy predict treatment failure. As with diagnosis, no single method can predict disease aggressiveness. Multiple serologic and genetic tests are being developed to refine the accuracy of prediction. Endoscopic findings can also predict the future course of disease. At present, clinical manifestations are the most useful way to make therapeutic decisions. PMID- 22298960 TI - Grading the degree of difficulty of ERCP procedures. PMID- 22298959 TI - The current economic burden of cirrhosis. AB - Cirrhosis is a worldwide problem that is associated with a substantial economic burden. Hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, and alcoholic liver disease are the main causes of cirrhosis, but cost-effective preventive strategies are only available for HBV infection. Treatment algorithms for HBV infection and HCV infection are numerous and may be economically advantageous, depending on the regimen utilized; however, effective treatment for alcoholic liver disease is lacking, with abstinence from alcohol consumption continuing to be the main treatment strategy. In addition, liver transplantation (the only cure for cirrhosis) continues to consume substantial economic resources despite a recent reduction in overall cost. More sensitive predictors of post liver transplantation disability could reduce this cost by allowing interventions that would promote productivity and increase health-related quality of life after liver transplantation. This paper highlights recent publications that evaluate the cost-effectiveness of strategies that prevent or treat the main causes of cirrhosis as well as publications that assess the impact of quality of life on the overall cost burden of the disease. PMID- 22298961 TI - Cyclosporine versus infliximab for the treatment of severe ulcerative colitis. PMID- 22298962 TI - Use of imaging studies to aid in the diagnosis of benign liver tumors. PMID- 22298963 TI - Barrett esophagus and life expectancy: implications for screening? PMID- 22298964 TI - Liver injury induced by the Japanese herbal drug kamishoyosan. PMID- 22298965 TI - Herbal and dietary supplement-induced liver injury. PMID- 22298966 TI - Metastasis of renal cell carcinoma to the pancreas 13 years postnenhrectomv. PMID- 22298967 TI - Metastatic renal cell carcinoma to the pancreas. PMID- 22298968 TI - Current and future role of serogenomics in ulcerative colitis. AB - Ulcerative colitis (UC), a chronic inflammatory bowel disease, occurs in genetically susceptible individuals who mount inappropriate immune responses to endoluminal antigens. Serologic and genetic markers have shown great potential for clinical application in Crohn's disease (CD), particularly for prognostication. However, their use is not as well established in UC. The aim of this paper is to highlight the clinical relevance of these markers for diagnostics and prognostication in UC. This review identified studies that cited the use of serum and genetic biomarkers in UC when these biomarkers were used in diagnostic, prognostic, and therapeutic response prediction applications. Several serologic and genetic markers associated with UC were identified, and this review presents and summarizes these data, focusing on the biomarkers' established and emerging diagnostic and prognostic utility. Although more established in CD, the data provided by serologic and genetic testing in UC has the potential to enhance clinical decision making. PMID- 22298969 TI - Pathophysiology, evaluation, and treatment of bloating: hope, hype, or hot air? AB - Abdominal bloating is commonly reported by men and women of all ages. Bloating occurs in nearly all patients with irritable bowel syndrome, and it also occurs in patients with other functional and organic disorders. Bloating is frequently disturbing to patients and frustrating to clinicians, as effective treatments are limited and are not universally successful. Although the terms bloating and abdominal distention are often used interchangeably, these symptoms likely involve different pathophysiologic processes, both of which are still not completely understood. The goal of this paper is to review the pathophysiology, evaluation, and treatment of bloating and abdominal distention. PMID- 22298970 TI - Approach to diagnosis of eosinophilic esophagitis. PMID- 22298971 TI - Strategies for management of Clostridium difficile infection in immunosuppressed patients. PMID- 22298972 TI - Update on endoscopic approaches to nutritional support. PMID- 22298973 TI - Hepatitis e virus infection: more common than previously realized? PMID- 22298974 TI - Strongyloides infection in a cardiac transplant recipient: making a case for pretransplantation screening and treatment. PMID- 22298975 TI - Strongyloides stercoralis hyperinfection syndrome and disseminated disease. PMID- 22298976 TI - Etanercept treatment to enable successful hepatitis C virus clearance in a patient with rheumatoid arthritis. PMID- 22298977 TI - Hepatitis C virus treatment complicated by rheumatoid arthritis. PMID- 22298978 TI - Gastro-hep news. PMID- 22298979 TI - Prognostic value of liver fibrosis biomarkers: a meta-analysis. AB - AIMS AND METHODS: Several serum biomarkers such as FibroTest, aspartate transaminase-platelet ratio index (APRI), FIB-4, and liver stiffness measurement by FibroScan have been validated as alternatives to biopsy for the diagnosis of fibrosis in patients with chronic liver disease. This paper aims to assess the 5 year prognostic values of these biomarkers. A meta-analysis combined all published prognostic studies. Baseline biopsy and APRI data were used as references. RESULTS: Only 3 biomarkers had several prognostic validations: FibroTest (4 studies; 2,396 patients), APRI (5 studies; 2,422 patients), and FIB 4 (3 studies; 1,184 patients). For the prediction of survival without liver related death, the areas under the receiver operating characteristic curves (AUROCs) were 0.86 for biopsy (95% confidence interval [CI], 0.77-0.95), 0.88 for FibroTest (95% CI, 0.79-0.98), 0.73 for FIB-4 (95% CI, 0.62-0.85), and 0.66 for APRI (95% CI, 0.57-0.75). APRI had a significantly lower prognostic value versus biopsy, with a mean difference between AUROCs of -0.21 (95% CI, -0.33 to -0.10; P<.001); FIB-4 had a significantly lower prognostic value versus biopsy, with a mean difference between AUROCs of -0.21 (95% CI, -0.20 to -0.02; P=.02). Only FibroTest did not show a significant difference in prognostic value versus biopsy, with a mean difference in AUROCs of +0.02 (95% CI, -0.05 to +0.09; P=.85). CONCLUSION: FibroTest is a validated biomarker for the prognosis of patients with chronic liver disease. PMID- 22298981 TI - Management of nondysplastic barrett esophagus with ablation therapy. PMID- 22298980 TI - Antibiotics for the treatment of irritable bowel syndrome. AB - Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder with an estimated worldwide prevalence of 10-20%. IBS can be associated with severe gastrointestinal symptoms, including abdominal pain, bloating, and altered bowel function. Although the causes of IBS remain undefined, recent research has increasingly suggested roles for gut flora in IBS. These roles involve postinfectious IBS, which can occur after a single episode of acute gastroenteritis, and small intestinal bacterial overgrowth, in which elevated populations of aerobic and anaerobic bacteria cause abdominal pain and altered bowel function. More recently, potential roles for methanogens in contributing to IBS subtypes have also been identified. In this paper, we review the different mechanisms by which gut flora may contribute to IBS and also discuss the efficacy and safety of various antibiotic therapies for treating IBS symptoms. PMID- 22298982 TI - Diagnosis and management of telaprevir-associated rash. PMID- 22298983 TI - New cytokine targets in inflammatory bowel disease. PMID- 22298984 TI - Endoscopic management of obesity. PMID- 22298985 TI - A lipoma of the transverse colon causing intermittent obstruction: a rare cause for surgical intervention. PMID- 22298986 TI - Large colonic lipomas. PMID- 22298987 TI - Immune tolerant hepatitis B: a clinical dilemma. AB - Chronic hepatitis B virus infection remains a global health concern, with perinatal transmission still a problem in many countries. Several new therapies for chronic hepatitis B virus infection have recently been introduced that can safely and effectively suppress viral replication with a low risk of resistance; thus, it has become increasingly tempting for many clinicians to treat patients in the immune tolerant stage of infection who have high levels of viremia yet persistently normal levels of transaminases. However, understanding the natural history of hepatitis B virus infection and how it pertains to disease progression, as well as how current therapies alter or do not alter this natural history, is important when deciding whether to treat these patients. This article will review the definition and natural history of immune tolerance, the current world guidelines and recommendations for treatment of immune tolerant patients, and data on the effectiveness of current therapies in this patient population. PMID- 22298989 TI - Utility of IL-28B Polymorphisms in the Era of Direct-Acting Antiviral Therapy. PMID- 22298988 TI - Therapeutic vaccines for gastrointestinal cancers. AB - Despite progress in the management of gastrointestinal malignancies, these diseases remain devastating maladies. Conventional treatment with chemotherapy and radiation is still only partially effective and highly toxic. In the era of increasing knowledge of the molecular biology of tumors and the interaction between the tumor and immune system, the development of targeted agents, including cancer vaccines, has emerged as a promising modality. In this paper, we discuss the principals of vaccine development, and we review most of the published trials on gastrointestinal cancer vaccines that have been conducted over the last decade. Many antigens and various treatment approaches have already been tested in colon, pancreatic, and other cancers. Some of these approaches have already shown some clinical benefit. In this paper, we discuss these different strategies and some of the future directions for targeting gastrointestinal malignancies with vaccines. PMID- 22298990 TI - The Use of Cecal and Terminal lleal Images for Verifying the Completion of Colonoscopy. PMID- 22298991 TI - Cricopharyngeal bar and zenker diverticulum. PMID- 22298992 TI - Preparing for biologic or immunosuppressant therapy. PMID- 22298993 TI - The many faces of celiac disease. PMID- 22298994 TI - Celiac disease: a challenge for all physicians. PMID- 22298995 TI - Complete esophageal obstruction following endoscopic variceal ligation. PMID- 22298996 TI - Primary prophylaxis of variceal bleeding. PMID- 22298997 TI - Defining readmission risk factors for liver transplantation recipients. AB - Liver transplantation (LT) is a costly but effective treatment for end-stage liver disease (ESLD). However, there are minimal data on the patterns of and risk factors for hospital readmission after LT. The aim of this study was to determine the frequency of and risk factors for rehospitalization after LT. Consecutive adult patients who underwent LT at a single center (n = 208) were prospectively studied over a 30-month period. Within 90 days of LT, 30.3% of LT recipients were readmitted to the hospital. Recipient and donor age, Model for End-Stage Liver Disease score, cold ischemia time, type of hepatic graft, length of hospitalization after LT, and occurrence of operative/postoperative complications had no association with the risk for readmission (P>.05). The length of stay in intensive care was negatively correlated with readmission (hazard ratio, 0.92; P=.028). ESLD from hepatitis C virus (HCV) infection as an indication for LT was the only factor associated with an increased risk for readmission (hazard ratio, 1.91 ; P=.010). Further studies are needed to explore the reasons for readmission among LT recipients, particularly those with HCV infection, in order to devise cost-savings policies for post-LT care. PMID- 22298999 TI - Efficacy of probiotics for the management of inflammatory bowel disease. PMID- 22298998 TI - Managing pain in inflammatory bowel disease. AB - Pain is a common complaint in inflammatory bowel disease, and it has significant consequences for patients' quality of life. A thorough evaluation to determine the source of patients' pain should include clinical, laboratory, radiologic, and endoscopic assessments as indicated. Differentiating among active inflammation, secondary complications, and functional pain can be complicated. Even when all active disease is adequately treated, clinicians are often left with the difficulty of managing chronic pain. This paper will review the benefits and limitations of several commonly used treatments and promising future therapies. A suggested treatment algorithm will provide some guidance in this challenging area of inflammatory bowel disease management. PMID- 22299000 TI - The European experience of achalasia treatment. PMID- 22299001 TI - Management of pruritus in patients with cholestatic liver disease. PMID- 22299002 TI - Preliminary Data on the Nanopowder Hemostatic Agent TC-325 to Control Gastrointestinal Bleeding. PMID- 22299003 TI - Metastatic adenosquamous carcinoma presenting as a solitary pancreatic mass. PMID- 22299004 TI - One more piece of the puzzle? Adenosquamous carcinoma in a pancreatic mass. PMID- 22299005 TI - The Role of Dairy Products in Healthy Weight and Body Composition in Children and Adolescents. AB - Overweight and obesity are major public health concerns with approximately 32% and 17% of U.S. children aged 2 - 19 being classified as overweight or obese, respectively. While the cause of overweight and obesity is multi-factorial, changes in eating habits and physical activity patterns have been proposed as contributing factors to the obesity epidemic. For example, the displacement of nutrient rich foods and beverages with non-nutrient dense items may be influencing childhood obesity. Many children do not consume the recommended servings of the Food Groups to Encourage, i.e. low-fat and fat-free dairy foods, fruits, vegetables, and whole grains identified by the 2005 Dietary Guidelines for Americans which results in low intakes of calcium, potassium, fiber, magnesium, and vitamin E. While attention has focused primarily on reducing energy intake and/or increasing energy expenditure for weight maintenance, a promising beneficial role for dairy products in weight management has emerged. Most research has focused on adults, but there is evidence in children and adolescents indicating either a beneficial or neutral effect of dairy food consumption on body weight or body composition. The current review provides and assessment of the scientific evidence on the effects of dairy food consumption on body weight and body composition in children and adolescents. PMID- 22299006 TI - Antidepressant Use During Breastfeeding. AB - BACKGROUND: The treatment of breastfeeding mothers with depression raises several dilemmas, including the possible risk of drug exposure through breast milk for the infant. This article provides background information and presents practical advice and recommendations for the clinician dealing with the treatment of depression and related disorders in the postpartum period. METHODS: An electronic search for relevant articles was performed. As the use of tricyclic antidepressants has considerably decreased during the last decade and no new information on breastfeeding has emerged for the tricyclics in this period, this review exclusively focuses on the newer, non-tricyclic compounds. RESULTS: Most newer antidepressants produce very low or undetectable plasma concentrations in nursing infants. The highest infant plasma levels have been reported for fluoxetine, citalopram and venlafaxine. Suspected adverse effects have been reported in a few infants, particularly for fluoxetine and citalopram. CONCLUSIONS: Infant exposure of antidepressants through breast milk is generally low to very low. We consider that when antidepressant treatment is indicated in women with postpartum depression, they should not be advised to discontinue breastfeeding. Paroxetine and sertraline are most likely suitable first-line agents. Although some concern has been expressed for fluoxetine, citalopram and venlafaxine, we nevertheless consider that if the mother has been treated with one of these drugs during pregnancy, breast-feeding could also be allowed during continued treatment with these drugs in the postpartum period. However, an individual risk-benefit assessment should always be performed. PMID- 22299007 TI - Life Story Board: A Tool in the Prevention of Domestic Violence. AB - The high rate of domestic violence in Aboriginal communities points to the need to explore new ways of understanding how this violence occurs in its context and to seek new and creative ways of preventing the perpetuation of this vicious cycle. The Life Story Board (LSB) is a game board with sets of cards, markers, and a notation system with which to construct a visual representation of someone's life experience at personal, family, and community levels. Initially invented as an interview tool in an expressive art program for war-affected children, the LSB has broader potential for use by those working with youth, adults, and families in a variety of contexts, and as a tool for program evaluation and applied research. This article describes LSB methods and how they may apply in the context of Canadian First Nations, Inuit, and Metis community efforts to respond to, understand, and prevent domestic violence. PMID- 22299008 TI - Occupy this and a sense of what is important. PMID- 22299009 TI - Childhood depression revisited: indicators, normative tests, and clinical course. PMID- 22299010 TI - Maternal Stress during Pregnancy, ADHD Symptomatology in Children and Genotype: Gene-Environment Interaction. AB - OBJECTIVE: Case control studies suggest a relationship between maternal stress during pregnancy and childhood ADHD. However, maternal smoking, parenting style and parental psychiatric disorder are possible confounding factors. Our objective was to control for these factors by using an intra-familial design, and investigate gene-environment interactions. METHODS: One hundred forty two children, ages 6 to 12, (71 with ADHD, and their 71 non-ADHD siblings) participated in the intra-familial study design. A larger sample of ADHD children (N=305) was genotyped for DAT1 and DRD4 to examine gene-environment interactions. Symptom severity was evaluated using the Child Behavior Checklist (CBCL) and the Conners' Global Index for Parents (CGI-P). The Kinney Medical and Gynecological Questionnaire was used to report stressful events during pregnancies. RESULTS: LOGISTIC REGRESSION INDICATED THAT MOTHERS WERE MORE LIKELY TO HAVE EXPERIENCED HIGH STRESS DURING PREGNANCY OF THEIR ADHD CHILD COMPARED TO THAT OF THE UNAFFECTED SIBLING (OR: 6.3, p=.01). In the larger sample, DRD4 7/7 genotype was associated with increased symptom severity in the high stress pregnancy (p=.01). CONCLUSIONS: Maternal stress during pregnancy was associated with the development of ADHD symptomatology after controlling for family history of ADHD and other environmental factors. This association could partly be mediated through the DRD4 genotype. PMID- 22299011 TI - Clinical characteristics of depressed youths in child psychiatry. AB - OBJECTIVE: To describe the clinical characteristics of depressed children and adolescents according to age groups and sex. METHODS: A retrospective chart review study was conducted on 75 youths aged 6-17 years referred for depressive disorders to child psychiatry in 2002-2003. Descriptive statistics and tests of association were completed to compare boys aged 6-11 years, boys aged 12-17 years and girls aged 12-17 years. RESULTS: One out of two youths has repeated a school year. About 60% of depressed boys aged 6-11 years are referred to child psychiatry services for behavioral difficulties and 71% of boys in this age group have a depressive disorder comorbid with disruptive behavior disorder. Adolescent boys and girls are more likely to present internalized symptoms than children. However, suicidal ideation is as widespread in children (71%) as in adolescent population, both boys (72%) and girls (85%). Parent-child relational problems are observed in the majority of the sample with a higher prevalence among adolescent girls. CONCLUSION: : It is as important to assess depressive symptoms and suicidal ideation among young boys with behavioral difficulties as in adolescent boys and girls. Family functioning is important to consider in evaluating and treating youth. PMID- 22299012 TI - Government monitoring of the mental health of children in Canada: five surveys (part I). AB - OBJECTIVE: Canadian governments spend billions of dollars yearly on programmatic interventions, intended to improve the mental health of children, without recommended monitoring of children's mental health. The Canadian Academy of Child and Adolescent Psychiatry monitored governments' progress in producing reports. METHOD: Five evolving surveys were done during 2002, 2004, 2005, 2006 and 2008. Initially, progress was monitored then later surveys examined challenges that inhibited monitoring, the need for a national strategy, an indicator framework and an agency to do the monitoring and the role of non-government organizations. The 2008 survey requested the three most important indicators governments desired, and created clarity in the definition of monitoring reports in contents, criteria, qualities of indicators and potential names. For comparison purposes, a Partnership Model to survey populations was evaluated. RESULTS: Over five surveys, 13 of 14 governments affirmed the desire for monitoring and 64 publications were reviewed and categorized. No reports met criteria for 'monitoring reports'. The Partnership Model was used successfully in 11 Provincial-Territorial governments. CONCLUSIONS: It was reassuring that governments supported monitoring and were producing reports. The Partnership Model may offer a suitable alternative for governments. Results of 2006 and 2008, discussion, conclusions and references are in Part II. PMID- 22299013 TI - Government Monitoring of the Mental Health of Children in Canada: Five Surveys (Part II). AB - OBJECTIVE: Canadian governments produced 64 reports containing data about the mental health of children but no reports could adequately be called monitoring reports. Surveys sought to clarify definitions, challenges and processes that could help lead to regular reports. METHOD: (Details in Part I). The 2006 survey clarified government current data use and future need, challenges to producing reports and the role of NGOs. The 2008 survey clarified the definition of reports, governments' most desired indicators, and national factors. RESULTS: Governments wanted the data for policy making, program construction, priority setting and resource allocation. The most challenging difficulties were governments themselves: coordinating among departments, lack of funding, lack of an agency and lowered priority. Governments most wanted indicators of child functioning, population health and early identification. Reports needed to meet specific criteria for contents, indicator qualities, population characteristics and regularity. CONCLUSIONS: Governments wanted a national strategy, national framework and agreement on a measuring agency. Good general agreement existed about reporting criteria. A partnership model may lead to quicker results given the difficulties within governments. NGOs and others need to continue collaborative advocacy. Monitoring is one of two steps that could help turn collections of services into self-regulating systems. PMID- 22299014 TI - Assessment and treatment of pediatric eating disorders: a survey of physicians and psychologists. AB - OBJECTIVE: Studies show that primary care clinicians struggle with the assessment and treatment of eating disorders in adults. There are no known studies examining current practices of clinicians with respect to eating disorders in children and adolescents. The following study describes the key practices of primary care clinicians in Ontario, Canada, around the screening, assessment, and treatment of eating disorders in children and adolescents. METHOD: A 24-item survey was developed to obtain information from family physicians and psychologists about presenting complaints and current practices related to the assessment and treatment of eating disorders. RESULTS: Findings of this study suggest that despite discipline-specific differences, a large proportion of clinicians do not routinely screen for eating disorders, and when eating disorders are assessed and treatment is initiated, family members are not routinely involved in the process. CONCLUSION: In Ontario, primary care clinicians may benefit from more training and support to better identify and treat children and adolescents with eating disorders. In particular, clinicians may require additional training around screening, multi-informant assessment methods, as well as appropriate therapy techniques. PMID- 22299015 TI - Attention deficit hyperactivity disorder (ADHD) in children, seasonal photoperiods, nocturnal movements and diurnal agitation. AB - OBJECTIVE: The main purpose of this study was to verify that the shortening photoperiods of winter contribute to increasing the nocturnal and diurnal agitation of children with ADHD and that lengthening photoperiods diminish it. METHOD: TO VERIFY THIS HYPOTHESIS WE CHOSE A LOCATION WHERE DAYLIGHT TIMES DROP DRASTICALLY IN THE FALL: Edmonton (Canada). The study's sample was fifteen children, varying in age from 7 to 9 years (M=8.13 years old). The participants were divided into two clinical groups and one control group. The first clinical group was made up of five (n=5) children diagnosed with ADHD and treated with psychostimulants. The second clinical group was made up of five (n=5) children with ADHD not treated with psychostimulants. The control group was composed of five (n=5) children showing no signs of ADHD or psychopathologies. The intensity of diurnal agitation linked to ADHD was evaluated by teachers using the French version questionnaire (SWAN-F) at T1 (first day of experiment). The children's nocturnal movements were evaluated using actimetry. Their sleep quality was measured with a sleep agenda. These last two measurements were carried out for five consecutive days when the length of the photoperiod was at its shortest (end of December). The same procedures were repeated at the end of June (T2), when the photoperiod was at its maximum. RESULTS: The principal results support the study's hypothesis and show a significant baseline difference (p=0.008) between the nocturnal motor movements of the ADHD children and those of the control children. CONCLUSIONS: According to these results, this type of research should be reproduced in other Nordic countries and should include a larger sample group of children diagnosed with ADHD. PMID- 22299016 TI - Clinical Case Rounds in Child and Adolescent Psychiatry: De Novo Self-Mutilation and Depressive Symptoms in a 17-year-old Adolescent Girl Receiving Depot Medroxyprogesterone Acetate. AB - INTRODUCTION: Contraception-induced mood changes have been identified since the 1960s. To our knowledge, there has been no reported case about self-mutilation associated to any form of contraception. We report the case of a 17-year-old adolescent girl who presented with de novo self-mutilation and depressive symptoms three and a half weeks after the administration of 150 mg of Depot Medroxyprogesterone Acetate (DMPA). METHOD: Clinical case report and literature review. Possible confounding factors are reviewed. RESULTS: The patient had no personal psychiatric history and no significant family psychiatric history. A DSM IV diagnosis of "mood disorder due to DMPA with depressive features" was formulated. There was no evidence of abnormal personality functioning. The mental status exam and collateral information validated the severity of her condition. DISCUSSION: DMPA is a birth control method especially useful for adolescent girls and possible secondary mood symptoms should not limit its access. However, since depressive symptoms substantially interfere with daily functioning and may have unfortunate consequences like self-mutilation and suicidal ideation, it is important to remain vigilant regarding the onset of mood symptoms following contraceptive use in adolescent girls. This vigilance should be more specific regarding adolescent girls with a history of mood disorders, anxiety disorders, self-mutilation or family diathesis of these conditions. PMID- 22299017 TI - Commentary: De Novo Self-Mutilation and Depressive Symptoms in a 17-year-old Adolescent Girl Receiving Depot-Medroxyprogesterone Acetate. PMID- 22299018 TI - Interview with Dr. Klaus Minde, MD: (interviewed by Normand Carrey MD). PMID- 22299019 TI - A randomized controlled trial of home visits by neighborhood mentor mothers to improve children's nutrition in South Africa. AB - Malnourished children and babies with birth weights under 2500 g are at high risk for negative outcomes over their lifespans. Philani, a paraprofessional home visiting program, was developed to improve nutritional outcomes for young children in South Africa. One "mentor mother" was recruited from each of 37 neighborhoods in Cape Town, South Africa. Mentor mothers were trained to conduct home visits to weigh children under six years old and to support mothers to problem-solve life challenges, especially around nutrition. Households with underweight children were assigned randomly on a 2:1 ratio to the Philani program (n = 500) or to a standard care condition (n = 179); selection effects occurred and children in the intervention households weighed less at recruitment. Children were evaluated over a one-year period (n = 679 at recruitment and n = 638 with at least one follow-up; 94%). Longitudinal random effects models indicated that, over 12 months, the children in the intervention condition gained significantly more weight than children in the control condition. Mentor mothers who are positive peer deviants may be a viable strategy that is efficacious and can build community, and the use of mentor mothers for other problems in South Africa is discussed. PMID- 22299020 TI - On the functional anatomy of the urge-for-action. AB - Several common neuropsychiatric disorders (e.g., obsessive-compulsive disorder, Tourette syndrome (TS), autistic spectrum disorder) are associated with unpleasant bodily sensations that are perceived as an urge for action. Similarly, many of our everyday behaviors are also characterized by bodily sensations that we experience as urges for action. Where do these urges originate? In this paper, we consider the nature and the functional anatomy of "urges-for-action," both in the context of everyday behaviors such as yawning, swallowing, and micturition, and in relation to clinical disorders in which the urge-for-action is considered pathological and substantially interferes with activities of daily living (e.g., TS). We review previous frameworks for thinking about behavioral urges and demonstrate that there is considerable overlap between the functional anatomy of urges associated with everyday behaviors such as swallowing, yawning, and micturition, and those urges associated with the generation of tics in TS. Specifically, we show that the limbic sensory and motor regions-insula and mid cingulate cortex-are common to all of these behaviors, and we argue that this "motivation-for-action" network should be considered distinct from an "intentional action" network, associated with regions of premotor and parietal cortex, which may be responsible for the perception of "willed intention" during the execution of goal-directed actions. PMID- 22299021 TI - Thrombospondin-1 and VEGF in inflammatory bowel disease. AB - BACKGROUND AND AIM: Angiogenesis is an important process in the pathogenesis of chronic inflammation. We aimed to study the angiogeneic balance in inflammatory bowel disease (IBD) by evaluating the expression of vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1) on colonic epithelial cells, together with the expression of inducible nitric oxide synthase (iNOS). METHODS: Twenty one ulcerative colitis (UC), 14 Crohn's disease (CD), 11 colorectal cancer patients, and 11 healthy controls colonic biopsy samples were evaluated immunohistochemically. RESULTS: The expressions of TSP-1, VEGF, and iNOS in UC and CD groups were higher than expression in healthy control group, all with statistical significance. However, in colorectal cancer group, VEGF and iNOS expressions were increased importantly, but TSP-1 expression was not statistically different from healthy control group's expression. Both TSP-1 and VEGF expressions were correlated with iNOS expression distinctly but did not correlate with each other. CONCLUSIONS: Both pro-angiogeneic VEGF and antiangiogeneic TSP-1 expressions were found increased in our IBD groups, but in colorectal cancer group, only VEGF expression was increased. TSP-1 increases in IBD patients as a response to inflammatory condition, but this increase was not enough to suppress pathologic angiogenesis and inflammation in IBD. PMID- 22299023 TI - Resolution limit for DNA barcodes in the Odijk regime. AB - We develop an approximation for the probability of optically resolving two fluorescent labels on the backbone of a DNA molecule confined in a nanochannel in the Odijk regime as a function of the fluorescence wavelength, channel size, and the properties of the DNA (persistence length and effective width). The theoretical predictions agree well with equivalent data produced by Monte Carlo simulations of a touching wormlike bead model of DNA in a high ionic strength buffer. Although the theory is only strictly valid in the limit where the effective width of the nanochannel is small compared with the persistence length of the DNA, simulations indicate that the theoretical predictions are reasonably accurate for channel widths up to two-thirds of the persistence length. Our results quantify the conjecture that DNA barcoding has kilobase pair resolution provided the nanochannel lies in the Odijk regime. PMID- 22299024 TI - Myocardial alternative RNA splicing and gene expression profiling in early stage hypoplastic left heart syndrome. AB - Hypoplastic Left Heart Syndrome (HLHS) is a congenital defect characterized by underdevelopment of the left ventricle and pathological compensation of the right ventricle. If untreated, HLHS is invariably lethal due to the extensive increase in right ventricular workload and eventual failure. Despite the clinical significance, little is known about the molecular pathobiological state of HLHS. Splicing of mRNA transcripts is an important regulatory mechanism of gene expression. Tissue specific alterations of this process have been associated with several cardiac diseases, however, transcriptional signature profiles related to HLHS are unknown. In this study, we performed genome-wide exon array analysis to determine differentially expressed genes and alternatively spliced transcripts in the right ventricle (RV) of six neonates with HLHS, compared to the RV and left ventricle (LV) from non-diseased control subjects. In HLHS, over 180 genes were differentially expressed and 1800 were differentially spliced, leading to changes in a variety of biological processes involving cell metabolism, cytoskeleton, and cell adherence. Additional hierarchical clustering analysis revealed that differential gene expression and mRNA splicing patterns identified in HLHS are unique compared to non-diseased tissue. Our findings suggest that gene expression and mRNA splicing are broadly dysregulated in the RV myocardium of HLHS neonates. In addition, our analysis identified transcriptome profiles representative of molecular biomarkers of HLHS that could be used in the future for diagnostic and prognostic stratification to improve patient outcome. PMID- 22299022 TI - Blood-brain barrier pathophysiology in traumatic brain injury. AB - The blood-brain barrier (BBB) is formed by tightly connected cerebrovascular endothelial cells, but its normal function also depends on paracrine interactions between the brain endothelium and closely located glia. There is a growing consensus that brain injury, whether it is ischemic, hemorrhagic, or traumatic, leads to dysfunction of the BBB. Changes in BBB function observed after injury are thought to contribute to the loss of neural tissue and to affect the response to neuroprotective drugs. New discoveries suggest that considering the entire gliovascular unit, rather than the BBB alone, will expand our understanding of the cellular and molecular responses to traumatic brain injury (TBI). This review will address the BBB breakdown in TBI, the role of blood-borne factors in affecting the function of the gliovascular unit, changes in BBB permeability and post-traumatic edema formation, and the major pathophysiological factors associated with TBI that may contribute to post-traumatic dysfunction of the BBB. The key role of neuroinflammation and the possible effect of injury on transport mechanisms at the BBB will also be described. Finally, the potential role of the BBB as a target for therapeutic intervention through restoration of normal BBB function after injury and/or by harnessing the cerebrovascular endothelium to produce neurotrophic growth factors will be discussed. PMID- 22299025 TI - Class II MHC self-antigen presentation in human B and T lymphocytes. AB - Human CD4(+) T cells process and present functional class II MHC-peptide complexes, but the endogenous peptide repertoire of these non-classical antigen presenting cells remains unknown. We eluted and sequenced HLA-DR-bound self peptides presented by CD4(+) T cells in order to compare the T cell-derived peptide repertoire to sequences derived from genetically identical B cells. We identified several novel epitopes derived from the T cell-specific proteome, including fragments of CD4 and IL-2. While these data confirm that T cells can present peptides derived from the T-cell specific proteome, the vast majority of peptides sequenced after elution from MHC were derived from the common proteome. From this pool, we identified several identical peptide epitopes in the T and B cell repertoire derived from common endogenous proteins as well as novel endogenous epitopes with promiscuous binding. These findings indicate that the endogenous HLA-DR-bound peptide repertoire, regardless of APC type and across MHC isotype, is largely derived from the same pool of self-protein. PMID- 22299026 TI - Access to barrier perches improves behavior repertoire in broilers. AB - Restriction of behavioral opportunities and uneven use of space are considerable welfare concerns in modern broiler production, particularly when birds are kept at high densities. We hypothesized that increased environmental complexity by provision of barrier perches would help address these issues by encouraging perching and enhancing use of the pen space across a range of stocking densities. 2,088 day-old broiler chicks were randomly assigned to one of the following barrier and density treatment combinations over four replications: simple barrier, complex barrier, or control (no barrier) and low (8 birds/m(2)), moderate (13 birds/m(2)), or high (18 birds/m(2)) density. Data were collected on focal birds via instantaneous scan sampling from 2 to 6 weeks of age. Mean estimates per pen for percent of observations seen performing each behavior, as well as percent of observations in the pen periphery vs. center, were quantified and submitted to an analysis of variance with week as the repeated measure. Barrier perches, density and age affected the behavioral time budget of broilers. Both simple and complex barrier perches effectively stimulated high perching rates. Aggression and disturbances were lower in both barrier treatments compared to controls (P<0.05). Increasing density to 18 birds/m(2) compared to the lower densities suppressed activity levels, with lower foraging (P<0.005), decreased perching (P<0.0001) and increased sitting (P = 0.001) earlier in the rearing period. Disturbances also increased at higher densities (P<0.05). Use of the central pen area was higher in simple barrier pens compared to controls (P<0.001), while increasing density above 8 birds/m(2) suppressed use of the central space (P<0.05). This work confirms some negative effects of increasing density and suggests that barrier perches have the potential to improve broiler welfare by encouraging activity (notably by providing accessible opportunities to perch), decreasing aggression and disturbances, and promoting more even distribution of birds throughout the pen space. PMID- 22299027 TI - Antibody to P. falciparum in pregnancy varies with intermittent preventive treatment regime and bed net use. AB - BACKGROUND: Antibodies towards placental-binding P. falciparum are thought to protect against pregnancy malaria; however, environmental factors may affect antibody development. METHODS AND FINDINGS: Using plasma from pregnant Malawian women, we measured IgG against placental-binding P. falciparum parasites by flow cytometry, and related results to intermittent preventive treatment (IPTp) regime, and bed net use. Bed net use was associated with decreased antibody levels at mid-pregnancy but not at 1 month post partum (1 mpp). At 1 mpp a more intensive IPTp regime was associated with decreased antibody levels in primigravidae, but not multigravidae. CONCLUSIONS/SIGNIFICANCE: Results suggest bed nets and IPTp regime influence acquisition of pregnancy-specific P. falciparum immunity. PMID- 22299028 TI - The PI3-kinase/mTOR-targeting drug NVP-BEZ235 inhibits growth and IgE-dependent activation of human mast cells and basophils. AB - The phosphoinositide 3-kinase (PI3-kinase) and the mammalian target of rapamycin (mTOR) are two major signaling molecules involved in growth and activation of mast cells (MC) and basophils (BA). We examined the effects of the dual PI3 kinase/mTOR blocker NVP-BEZ235 on growth of normal and neoplastic BA and MC as well as immunoglobulin E (IgE)-dependent cell activation. Growth of MC and BA were determined by measuring (3)H-thymidine uptake and apoptosis. Cell activation was determined in histamine release experiments and by measuring upregulation of CD63 and CD203c after challenging with IgE plus anti-IgE or allergen. We found that NVP-BEZ235 exerts profound inhibitory effects on growth of primary and cloned neoplastic MC. In the MC leukemia cell line HMC-1, NVP-BEZ235 showed similar IC(50) values in the HMC-1.1 subclone lacking KIT D816V (0.025 uM) and the HMC-1.2 subclone expressing KIT D816V (0.005 uM). Moreover, NVP-BEZ235 was found to exert strong growth-inhibitory effects on neoplastic MC in a xenotransplant-mouse model employing NMR1-Foxn1(nu) mice. NVP-BEZ235 also exerted inhibitory effects on cytokine-dependent differentiation of normal BA and MC, but did not induce growth inhibition or apoptosis in mature MC or normal bone marrow cells. Finally, NVP-BEZ235 was found to inhibit IgE-dependent histamine release in BA and MC (IC(50) 0.5-1 uM) as well as anti-IgE-induced upregulation of CD203c in BA and IgE-dependent upregulation of CD63 in MC. In summary, NVP-BEZ235 produces growth-inhibitory effects in immature neoplastic MC and inhibits IgE dependent activation of mature BA and MC. Whether these potentially beneficial drug effects have clinical implications is currently under investigation. PMID- 22299029 TI - Differential role of PKC-induced c-Jun in HTLV-1 LTR activation by 12-O tetradecanoylphorbol-13-acetate in different human T-cell lines. AB - We have previously shown that TPA activates HTLV-1 LTR in Jurkat T-cells by inducing the binding of Sp1-p53 complex to the Sp1 site residing within the Ets responsive region 1 (ERR-1) of the LTR and that this activation is inhibited by PKCalpha and PKCepsilon. However, in H9 T-cells TPA has been noted to activate the LTR in two consecutive stages. The first stage is activation is mediated by PKCetta and requires the three 21 bp TRE repeats. The second activation mode resembles that of Jurkat cells, except that it is inhibited by PKCdelta. The present study revealed that the first LTR activation in H9 cells resulted from PKCetta-induced elevation of non-phosphorylated c-Jun which bound to the AP-1 site residing within each TRE. In contrast, this TRE-dependent activation did not occur in Jurkat cells, since there was no elevation of non-phosphorylated c-Jun in these cells. However, we found that PKCalpha and PKCepsilon, in Jurkat cells, and PKCetta and PKCdelta, in H9 cells, increased the level of phosphorylated c Jun that interacted with the Sp1-p53 complex. This interaction prevented the Sp1 p53 binding to ERR-1 and blocked, thereby, the ERR-1-mediated LTR activation. Therefore, this PKC-inhibited LTR activation started in both cell types after depletion of the relevant PKCs by their downregulation. In view of these variable activating mechanisms we assume that there might be additional undiscovered yet modes of HTLV-1 LTR activation which vary in different cell types. Moreover, in line with this presumption we speculate that in HTLV-1 carriers the LTR of the latent provirus may also be reactivated by different mechanisms that vary between its different host T-lymphocyte subclones. Since this reactivation may initiate the ATL process, understanding of these mechanisms is essential for establishing strategies to block the possibility of reactivating the latent virus as preventive means for ATL development in carriers. PMID- 22299030 TI - BMP-9 induced endothelial cell tubule formation and inhibition of migration involves Smad1 driven endothelin-1 production. AB - BACKGROUND: Bone morphogenetic proteins (BMPs) and their receptors, such as bone morphogenetic protein receptor (BMPR) II, have been implicated in a wide variety of disorders including pulmonary arterial hypertension (PAH). Similarly, endothelin-1 (ET-1), a mitogen and vasoconstrictor, is upregulated in PAH and endothelin receptor antagonists are used in its treatment. We sought to determine whether there is crosstalk between BMP signalling and the ET-1 axis in human pulmonary artery endothelial cells (HPAECs), possible mechanisms involved in such crosstalk and functional consequences thereof. METHODOLOGY/PRINCIPAL FINDING: Using western blot, real time RT-PCR, ELISA and small RNA interference methods we provide evidence that in HPAECs BMP-9, but not BMP-2, -4 and -6 significantly stimulated ET-1 release under physiological concentrations. This release is mediated by both Smad1 and p38 MAPK and is independent of the canonical Smad4 pathway. Moreover, knocking down the ALK1 receptor or BMPR II attenuates BMP-9 stimulated ET-1 release, whilst causing a significant increase in prepro ET-1 mRNA transcription and mature peptide release. Finally, BMP-9 induced ET-1 release is involved in both inhibition of endothelial cell migration and promotion of tubule formation. CONCLUSIONS/SIGNIFICANCE: Although our data does not support an important role for BMP-9 as a source of increased endothelial ET-1 production seen in human PAH, BMP-9 stimulated ET-1 production is likely to be important in angiogenesis and vascular stability. However, increased ET-1 production by endothelial cells as a consequence of BMPR II dysfunction may be clinically relevant in the pathogenesis of PAH. PMID- 22299031 TI - A bovine model of respiratory Chlamydia psittaci infection: challenge dose titration. AB - This study aimed to establish and evaluate a bovine respiratory model of experimentally induced acute C. psittaci infection. Calves are natural hosts and pathogenesis may resemble the situation in humans. Intrabronchial inoculation of C. psittaci strain DC15 was performed in calves aged 2-3 months via bronchoscope at four different challenge doses from 10(6) to 10(9) inclusion-forming units (ifu) per animal. Control groups received either UV-inactivated C. psittaci or cell culture medium. While 10(6) ifu/calf resulted in a mild respiratory infection only, the doses of 10(7) and 10(8) induced fever, tachypnea, dry cough, and tachycardia that became apparent 2-3 days post inoculation (dpi) and lasted for about one week. In calves exposed to 10(9) ifu C. psittaci, the respiratory disease was accompanied by severe systemic illness (apathy, tremor, markedly reduced appetite). At the time point of most pronounced clinical signs (3 dpi) the extent of lung lesions was below 10% of pulmonary tissue in calves inoculated with 10(6) and 10(7) ifu, about 15% in calves inoculated with 10(8) and more than 30% in calves inoculated with 10(9) ifu C. psittaci. Beside clinical signs and pathologic lesions, the bacterial load of lung tissue and markers of pulmonary inflammation (i.e., cell counts, concentration of proteins and eicosanoids in broncho-alveolar lavage fluid) were positively associated with ifu of viable C. psittaci. While any effect of endotoxin has been ruled out, all effects could be attributed to infection by the replicating bacteria. In conclusion, the calf represents a suitable model of respiratory chlamydial infection. Dose titration revealed that both clinically latent and clinically manifest infection can be reproduced experimentally by either 10(6) or 10(8) ifu/calf of C. psittaci DC15 while doses above 10(8) ifu C. psittaci cannot be recommended for further studies for ethical reasons. This defined model of different clinical expressions of chlamydial infection allows studying host-pathogen interactions. PMID- 22299032 TI - Zebrafish models for dyskeratosis congenita reveal critical roles of p53 activation contributing to hematopoietic defects through RNA processing. AB - Dyskeratosis congenita (DC) is a rare bone marrow failure syndrome in which hematopoietic defects are the main cause of mortality. The most studied gene responsible for DC pathogenesis is DKC1 while mutations in several other genes encoding components of the H/ACA RNP telomerase complex, which is involved in ribosomal RNA(rRNA) processing and telomere maintenance, have also been implicated. GAR1/nola1 is one of the four core proteins of the H/ACA RNP complex. Through comparative analysis of morpholino oligonucleotide induced knockdown of dkc1 and a retrovirus insertion induced mutation of GAR1/nola1 in zebrafish, we demonstrate that hematopoietic defects are specifically recapitulated in these models and that these defects are significantly reduced in a p53 null mutant background. We further show that changes in telomerase activity are undetectable at the early stages of DC pathogenesis but rRNA processing is clearly defective. Our data therefore support a model that deficiency in dkc1 and nola1 in the H/ACA RNP complex likely contributes to the hematopoietic phenotype through p53 activation associated with rRNA processing defects rather than telomerase deficiency during the initial stage of DC pathogenesis. PMID- 22299033 TI - A dig into the past mitochondrial diversity of Corsican goats reveals the influence of secular herding practices. AB - The goat (Capra hircus) is one of the earliest domesticated species ca. 10,500 years ago in the Middle-East where its wild ancestor, the bezoar (Capra aegagrus), still occurs. During the Neolithic dispersal, the domestic goat was then introduced in Europe, including the main Mediterranean islands. Islands are interesting models as they maintain traces of ancient colonization, historical exchanges or of peculiar systems of husbandry. Here, we compare the mitochondrial genetic diversity of both medieval and extant goats in the Island of Corsica that presents an original and ancient model of breeding with free-ranging animals. We amplified a fragment of the Control Region for 21 medieval and 28 current goats. Most of them belonged to the A haplogroup, the most worldwide spread and frequent today, but the C haplogroup is also detected at low frequency in the current population. Present Corsican goats appeared more similar to medieval goats than to other European goat populations. Moreover, 16 out of the 26 haplotypes observed were endemic to Corsica and the inferred demographic history suggests that the population has remained constant since the Middle Ages. Implications of these results on management and conservation of endangered Corsican goats currently decimated by a disease are addressed. PMID- 22299034 TI - A novel extracellular metallopeptidase domain shared by animal host-associated mutualistic and pathogenic microbes. AB - The mucosal microbiota is recognised as an important factor for our health, with many disease states linked to imbalances in the normal community structure. Hence, there is considerable interest in identifying the molecular basis of human microbe interactions. In this work we investigated the capacity of microbes to thrive on mucosal surfaces, either as mutualists, commensals or pathogens, using comparative genomics to identify co-occurring molecular traits. We identified a novel domain we named M60-like/PF13402 (new Pfam entry PF13402), which was detected mainly among proteins from animal host mucosa-associated prokaryotic and eukaryotic microbes ranging from mutualists to pathogens. Lateral gene transfers between distantly related microbes explained their shared M60-like/PF13402 domain. The novel domain is characterised by a zinc-metallopeptidase-like motif and is distantly related to known viral enhancin zinc-metallopeptidases. Signal peptides and/or cell surface anchoring features were detected in most microbial M60-like/PF13402 domain-containing proteins, indicating that these proteins target an extracellular substrate. A significant subset of these putative peptidases was further characterised by the presence of associated domains belonging to carbohydrate-binding module family 5/12, 32 and 51 and other glycan binding domains, suggesting that these novel proteases are targeted to complex glycoproteins such as mucins. An in vitro mucinase assay demonstrated degradation of mammalian mucins by a recombinant form of an M60-like/PF13402-containing protein from the gut mutualist Bacteroides thetaiotaomicron. This study reveals that M60-like domains are peptidases targeting host glycoproteins. These peptidases likely play an important role in successful colonisation of both vertebrate mucosal surfaces and the invertebrate digestive tract by both mutualistic and pathogenic microbes. Moreover, 141 entries across various peptidase families described in the MEROPS database were also identified with carbohydrate-binding modules defining a new functional context for these glycan binding domains and providing opportunities to engineer proteases targeting specific glycoproteins for both biomedical and industrial applications. PMID- 22299035 TI - Plastic and heritable components of phenotypic variation in Nucella lapillus: an assessment using reciprocal transplant and common garden experiments. AB - Assessment of plastic and heritable components of phenotypic variation is crucial for understanding the evolution of adaptive character traits in heterogeneous environments. We assessed the above in relation to adaptive shell morphology of the rocky intertidal snail Nucella lapillus by reciprocal transplantation of snails between two shores differing in wave action and rearing snails of the same provenance in a common garden. Results were compared with those reported for similar experiments conducted elsewhere. Microsatellite variation indicated limited gene flow between the populations. Intrinsic growth rate was greater in exposed-site than sheltered-site snails, but the reverse was true of absolute growth rate, suggesting heritable compensation for reduced foraging opportunity at the exposed site. Shell morphology of reciprocal transplants partially converged through plasticity toward that of native snails. Shell morphology of F(2)s in the common garden partially retained characteristics of the P generation, suggesting genetic control. A maternal effect was revealed by greater resemblance of F(1)s than F(2)s to the P-generation. The observed synergistic effects of plastic, maternal and genetic control of shell-shape may be expected to maximise fitness when environmental characteristics become unpredictable through dispersal. PMID- 22299036 TI - Interventions to influence consulting and antibiotic use for acute respiratory tract infections in children: a systematic review and meta-analysis. AB - BACKGROUND: Respiratory tract infections (RTIs) are common in children and generally self-limiting, yet often result in consultations to primary care. Frequent consultations divert resources from care for potentially more serious conditions and increase the opportunity for antibiotic overuse. Overuse of antibiotics is associated with adverse effects and antimicrobial resistance, and has been shown to influence how patients seek care in ensuing illness episodes. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a systematic review and meta analysis to assess the effectiveness of interventions directed towards parents or caregivers which were designed to influence consulting and antibiotic use for respiratory tract infections (RTIs) in children in primary care. Main outcomes were parental consulting rate, parental knowledge, and proportion of children subsequently consuming antibiotics. Of 5,714 references, 23 studies (representing 20 interventions) met inclusion criteria. Materials designed to engage children in addition to parents were effective in modifying parental knowledge and behaviour, resulting in reductions in consulting rates ranging from 13 to 40%. Providing parents with delayed prescriptions significantly decreased reported antibiotic use (Risk Ratio (RR) 0.46 (0.40, 0.54); moreover, a delayed or no prescribing approach did not diminish parental satisfaction. CONCLUSIONS: IN ORDER TO BE MOST EFFECTIVE, INTERVENTIONS TO INFLUENCE PARENTAL CONSULTING AND ANTIBIOTIC USE SHOULD: engage children, occur prior to an illness episode, employ delayed prescribing, and provide guidance on specific symptoms. These results support the wider implementation of interventions to reduce inappropriate antibiotic use in children. PMID- 22299037 TI - Selection indicates preference in diverse habitats: a ground-nesting bird (Charadrius melodus) using reservoir shoreline. AB - Animals use proximate cues to select resources that maximize individual fitness. When animals have a diverse array of available habitats, those selected could give insights into true habitat preferences. Since the construction of the Garrison Dam on the Missouri River in North Dakota, Lake Sakakawea (SAK) has become an important breeding area for federally threatened piping plovers (Charadrius melodus; hereafter plovers). We used conditional logistic regression to examine nest-site selection at fine scales (1, 3, and 10 m) during summers 2006-2009 by comparing characteristics at 351 nests to those of 668 random sites within nesting territories. Plovers selected sites (1 m(2)) that were lower than unused random sites, increasing the risk of nest inundation. Plovers selected nest sites that were flat, had little silt, and at least 1 cobble; they also selected for 3-m radius nest areas that were relatively flat and devoid of vegetation and litter. Ninety percent of nests had <38% coverage of silt and <10% slope at the site, and <15% coverage of vegetation or litter and <31% slope within the 3-m radius. Gravel was selected for at nest sites (11% median), but against in the area 10-m from the nest, suggesting plovers select for patches or strips of gravel. Although elevation is rarely evaluated in studies of ground nesting birds, our results underscore its importance in habitat-selection studies. Relative to where plovers historically nested, habitat at SAK has more diverse topography, substrate composition, vegetation communities, and greater water-level fluctuations. Accordingly, our results provide an example of how habitat-selection results can be interpreted as habitat preferences because they are not influenced by desired habitats being scarce or absent. Further, our results will be useful for directing habitat conservation for plovers and interpreting other habitat-selection studies. PMID- 22299038 TI - The cost of universal health care in India: a model based estimate. AB - INTRODUCTION: As high out-of-pocket healthcare expenses pose heavy financial burden on the families, Government of India is considering a variety of financing and delivery options to universalize health care services. Hence, an estimate of the cost of delivering universal health care services is needed. METHODS: We developed a model to estimate recurrent and annual costs for providing health services through a mix of public and private providers in Chandigarh located in northern India. Necessary health services required to deliver good quality care were defined by the Indian Public Health Standards. National Sample Survey data was utilized to estimate disease burden. In addition, morbidity and treatment data was collected from two secondary and two tertiary care hospitals. The unit cost of treatment was estimated from the published literature. For diseases where data on treatment cost was not available, we collected data on standard treatment protocols and cost of care from local health providers. RESULTS: We estimate that the cost of universal health care delivery through the existing mix of public and private health institutions would be INR 1713 (USD 38, 95%CI USD 18-73) per person per annum in India. This cost would be 24% higher, if branded drugs are used. Extrapolation of these costs to entire country indicates that Indian government needs to spend 3.8% (2.1%-6.8%) of the GDP for universalizing health care services. CONCLUSION: The cost of universal health care delivered through a combination of public and private providers is estimated to be INR 1713 per capita per year in India. Important issues such as delivery strategy for ensuring quality, reducing inequities in access, and managing the growth of health care demand need be explored. PMID- 22299039 TI - HNF1B and endometrial cancer risk: results from the PAGE study. AB - We examined the association between HNF1B variants identified in a recent genome wide association study and endometrial cancer in two large case-control studies nested in prospective cohorts: the Multiethnic Cohort Study (MEC) and the Women's Health Initiative (WHI) as part of the Population Architecture using Genomics and Epidemiology (PAGE) study. A total of 1,357 incident cases of invasive endometrial cancer and 7,609 controls were included in the analysis (MEC: 426 cases/3,854 controls; WHI: 931 cases/3,755 controls). The majority of women in the WHI were European American, while the MEC included sizable numbers of African Americans, Japanese and Latinos. We estimated the odds ratios (ORs) per allele and 95% confidence intervals (CIs) of each SNP using unconditional logistic regression adjusting for age, body mass index, and four principal components of ancestry informative markers. The combined ORs were estimated using fixed effect models. Rs4430796 and rs7501939 were associated with endometrial cancer risk in MEC and WHI with no heterogeneity observed across racial/ethnic groups (P >= 0.21) or between studies (P >= 0.70). The OR(per allele) was 0.82 (95% CI: 0.75, 0.89; P = 5.63 * 10(-6)) for rs4430796 (G allele) and 0.79 (95% CI: 0.73, 0.87; P = 3.77 * 10(-7)) for rs7501939 (A allele). The associations with the risk of Type I and Type II tumors were similar (P >= 0.19). Adjustment for additional endometrial cancer risk factors such as parity, oral contraceptive use, menopausal hormone use, and smoking status had little effect on the results. In conclusion, HNF1B SNPs are associated with risk of endometrial cancer and that the associated relative risks are similar for Type I and Type II tumors. PMID- 22299040 TI - Analysis of beta-cell gene expression reveals inflammatory signaling and evidence of dedifferentiation following human islet isolation and culture. AB - The stresses encountered during islet isolation and culture may have deleterious effects on beta-cell physiology. However, the biological response of human islet cells to isolation remains poorly characterized. A better understanding of the network of signaling pathways induced by islet isolation and culturing may lead to strategies aimed at improving islet graft survival and function. Laser capture microdissection (LCM) was used to extract beta-cell RNA from 1) intact pancreatic islets, 2) freshly isolated islets, 3) islets cultured for 3 days, and changes in gene expression were examined by microarray analysis. We identified a strong inflammatory response induced by islet isolation that continues during in-vitro culture manifested by upregulation of several cytokines and cytokine-receptors. The most highly upregulated gene, interleukin-8 (IL-8), was induced by 3.6-fold following islet isolation and 56-fold after 3 days in culture. Immunofluorescence studies showed that the majority of IL-8 was produced by beta-cells themselves. We also observed that several pancreas-specific transcription factors were down regulated in cultured islets. Concordantly, several pancreatic progenitor cell specific transcription factors like SOX4, SOX9, and ID2 were upregulated in cultured islets, suggesting progressive transformation of mature beta-cell phenotype toward an immature endocrine cell phenotype. Our findings suggest islet isolation and culture induces an inflammatory response and loss of the mature endocrine cell phenotype. A better understanding of the signals required to maintain a mature beta-cell phenotype may help improve the efficacy of islet transplantation. PMID- 22299041 TI - TRIM32 regulates skeletal muscle stem cell differentiation and is necessary for normal adult muscle regeneration. AB - Limb girdle muscular dystrophy type 2H (LGMD2H) is an inherited autosomal recessive disease of skeletal muscle caused by a mutation in the TRIM32 gene. Currently its pathogenesis is entirely unclear. Typically the regeneration process of adult skeletal muscle during growth or following injury is controlled by a tissue specific stem cell population termed satellite cells. Given that TRIM32 regulates the fate of mammalian neural progenitor cells through controlling their differentiation, we asked whether TRIM32 could also be essential for the regulation of myogenic stem cells. Here we demonstrate for the first time that TRIM32 is expressed in the skeletal muscle stem cell lineage of adult mice, and that in the absence of TRIM32, myogenic differentiation is disrupted. Moreover, we show that the ubiquitin ligase TRIM32 controls this process through the regulation of c-Myc, a similar mechanism to that previously observed in neural progenitors. Importantly we show that loss of TRIM32 function induces a LGMD2H-like phenotype and strongly affects muscle regeneration in vivo. Our studies implicate that the loss of TRIM32 results in dysfunctional muscle stem cells which could contribute to the development of LGMD2H. PMID- 22299042 TI - Injection of Pseudomonas aeruginosa Exo toxins into host cells can be modulated by host factors at the level of translocon assembly and/or activity. AB - Pseudomonas aeruginosa type III secretion apparatus exports and translocates four exotoxins into the cytoplasm of the host cell. The translocation requires two hydrophobic bacterial proteins, PopB and PopD, that are found associated with host cell membranes following infection. In this work we examined the influence of host cell elements on exotoxin translocation efficiency. We developed a quantitative flow cytometry based assay of translocation that used protein fusions between either ExoS or ExoY and the beta-lactamase reporter enzyme. In parallel, association of translocon proteins with host plasma membranes was evaluated by immunodetection of PopB/D following sucrose gradient fractionation of membranes. A pro-myelocytic cell line (HL-60) and a pro-monocytic cell line (U937) were found resistant to toxin injection even though PopB/D associated with host cell plasma membranes. Differentiation of these cells to either macrophage- or neutrophil-like cell lines resulted in injection-sensitive phenotype without significantly changing the level of membrane-inserted translocon proteins. As previous in vitro studies have indicated that the lysis of liposomes by PopB and PopD requires both cholesterol and phosphatidyl-serine, we first examined the role of cholesterol in translocation efficiency. Treatment of sensitive HL-60 cells with methyl-beta-cyclodextrine, a cholesterol-depleting agent, resulted in a diminished injection of ExoS-Bla. Moreover, the PopB translocator was found in the membrane fraction, obtained from sucrose-gradient purifications, containing the lipid-raft marker flotillin. Examination of components of signalling pathways influencing the toxin injection was further assayed through a pharmacological approach. A systematic detection of translocon proteins within host membranes showed that, in addition to membrane composition, some general signalling pathways involved in actin polymerization may be critical for the formation of a functional pore. In conclusion, we provide new insights in regulation of translocation process and suggest possible cross-talks between eukaryotic cell and the pathogen at the level of exotoxin translocation. PMID- 22299043 TI - Patient's origin and lifestyle associated with CTX-M-producing Escherichia coli: a case-control-control study. AB - BACKGROUND: Global dissemination of Escherichia coli producing CTX-M extended spectrum beta-lactamases (ESBL) is a public health concern. The aim of the study was to determine factors associated with CTX-M- producing E. coli infections among patients hospitalised in the Assistance Publique-Hopitaux de Paris, the largest hospital system in France (23 000 beds), through a prospective case control-control study. METHODS/PRINCIPAL FINDINGS: From November 2008 to June 2009, 152 inpatients with a clinical sample positive for CTX-M-producing E. coli (cases), 152 inpatients with a clinical sample positive for non ESBL-producing E. coli on the day or within the three days following case detection (controls C1), and 152 inpatients with culture-negative clinical samples since the beginning of hospitalisation and until three days after case detection (controls C2) were included in ten hospitals of the Paris area. Factors studied were related to patient's origin, lifestyle and medical history as well as care during hospitalisation. Those independently associated with CTX-M-producing E. coli were determined. Three independent factors were common to the two case-control comparisons: birth outside of Europe (cases vs C1: OR(1) = 2.4; 95%CI = [1.3-4.5] and cases vs C2: OR(2) = 3.1; 95%CI = [1.4-7.0]), chronic infections (OR(1) = 2.9; 95%CI = [1.3-6.9] and OR(2) = 8.7; 95%CI = [2.0-39.7]), and antibiotic treatment between hospital admission and inclusion (OR(1) = 2.0; 95%CI = [1.0 3.8] and OR(2) = 3.3; 95%CI = [1.5-7.2]). Cases were also more likely to be (i) functionally dependent before hospitalisation than C2 (OR(2) = 7.0; 95%CI = [2.1 23.5]) and (ii) living in collective housing before hospitalisation than C2 (OR(2) = 15.2; 95%CI = [1.8-130.7]) when CTX-M-producing E. coli was present at admission. CONCLUSION: For the first time, patient's origin and lifestyle were demonstrated to be independently associated with isolation of CTX-M-producing E. coli, in addition to health care-related factors. PMID- 22299044 TI - An alteration in the lateral geniculate nucleus of experimental glaucoma monkeys: in vivo positron emission tomography imaging of glial activation. AB - We examined lateral geniculate nucleus (LGN) degeneration as an indicator for possible diagnosis of glaucoma in experimental glaucoma monkeys using positron emission tomography (PET). Chronic intraocular pressure (IOP) elevation was induced by laser trabeculoplasty in the left eyes of 5 cynomolgus monkeys. Glial cell activation was detected by PET imaging with [(11)C]PK11195, a PET ligand for peripheral-type benzodiazepine receptor (PBR), before and at 4 weeks after laser treatment (moderate glaucoma stage). At mild, moderate, and advanced experimental glaucoma stages (classified by histological changes based on the extent of axonal loss), brains were stained with cresyl violet, or antibodies against PBR, Iba-1 (a microglial marker), and GFAP (an activated astrocyte marker). In laser-treated eyes, IOP was persistently elevated throughout all observation periods. PET imaging showed increased [(11)C]PK11195 binding potential in the bilateral LGN at 4 weeks after laser treatment; the increase in the ipsilateral LGN was statistically significant (P<0.05, n = 4). Immunostaining showed bilateral activations of microglia and astrocytes in LGN layers receiving input from the laser-treated eye. PBR-positive cells were observed in LGN layers receiving input from laser-treated eye at all experimental glaucoma stages including the mild glaucoma stage and their localization coincided with Iba-1 positive microglia and GFAP-positive astrocytes. These data suggest that glial activation occurs in the LGN at a mild glaucoma stage, and that the LGN degeneration could be detected by a PET imaging with [(11)C]PK11195 during the moderate experimental glaucoma stage after unilateral ocular hypertension. Therefore, activated glial markers such as PBR in the LGN may be useful in noninvasive molecular imaging for diagnosis of glaucoma. PMID- 22299045 TI - Defining the cellular environment in the organ of Corti following extensive hair cell loss: a basis for future sensory cell replacement in the Cochlea. AB - BACKGROUND: Following the loss of hair cells from the mammalian cochlea, the sensory epithelium repairs to close the lesions but no new hair cells arise and hearing impairment ensues. For any cell replacement strategy to be successful, the cellular environment of the injured tissue has to be able to nurture new hair cells. This study defines characteristics of the auditory sensory epithelium after hair cell loss. METHODOLOGY/PRINCIPAL FINDINGS: Studies were conducted in C57BL/6 and CBA/Ca mice. Treatment with an aminoglycoside-diuretic combination produced loss of all outer hair cells within 48 hours in both strains. The subsequent progressive tissue re-organisation was examined using immunohistochemistry and electron microscopy. There was no evidence of significant de-differentiation of the specialised columnar supporting cells. Kir4.1 was down regulated but KCC4, GLAST, microtubule bundles, connexin expression patterns and pathways of intercellular communication were retained. The columnar supporting cells became covered with non-specialised cells migrating from the outermost region of the organ of Corti. Eventually non-specialised, flat cells replaced the columnar epithelium. Flat epithelium developed in distributed patches interrupting regions of columnar epithelium formed of differentiated supporting cells. Formation of the flat epithelium was initiated within a few weeks post-treatment in C57BL/6 mice but not for several months in CBA/Ca's, suggesting genetic background influences the rate of re-organisation. CONCLUSIONS/SIGNIFICANCE: The lack of dedifferentiation amongst supporting cells and their replacement by cells from the outer side of the organ of Corti are factors that may need to be considered in any attempt to promote endogenous hair cell regeneration. The variability of the cellular environment along an individual cochlea arising from patch-like generation of flat epithelium, and the possible variability between individuals resulting from genetic influences on the rate at which remodelling occurs may pose challenges to devising the appropriate regenerative therapy for a deaf patient. PMID- 22299046 TI - Synergistic TLR2/6 and TLR9 activation protects mice against lethal influenza pneumonia. AB - Lower respiratory tract infections caused by influenza A continue to exact unacceptable worldwide mortality, and recent epidemics have emphasized the importance of preventative and containment strategies. We have previously reported that induction of the lungs' intrinsic defenses by aerosolized treatments can protect mice against otherwise lethal challenges with influenza A virus. More recently, we identified a combination of Toll like receptor (TLR) agonists that can be aerosolized to protect mice against bacterial pneumonia. Here, we tested whether this combination of synthetic TLR agonists could enhance the survival of mice infected with influenza A/HK/8/68 (H3N2) or A/California/04/2009 (H1N1) influenza A viruses. We report that the TLR treatment enhanced survival whether given before or after the infectious challenge, and that protection tended to correlate with reductions in viral titer 4 d after infection. Surprisingly, protection was not associated with induction of interferon gene expression. Together, these studies suggest that synergistic TLR interactions can protect against influenza virus infections by mechanisms that may provide the basis for novel therapeutics. PMID- 22299047 TI - MIR-99a and MIR-99b modulate TGF-beta induced epithelial to mesenchymal plasticity in normal murine mammary gland cells. AB - Epithelial to mesenchymal transition (EMT) is a key process during embryonic development and disease development and progression. During EMT, epithelial cells lose epithelial features and express mesenchymal cell markers, which correlate with increased cell migration and invasion. Transforming growth factor-beta (TGF beta) is a multifunctional cytokine that induces EMT in multiple cell types. The TGF-beta pathway is regulated by microRNAs (miRNAs), which are small non-coding RNAs regulating the translation of specific messenger RNAs.Herein, we identified mir-99a and mir-99b as two novel TGF-beta target miRNA genes, the expression of which increased during TGF-beta induced EMT of NMUMG cells. Mir-99a and mir-99b inhibition decreased TGF-beta activity by inhibiting SMAD3 phosphorylation, resulting in decreased migration and increased proliferation in response to TGF beta. However, mir-99a and mir-99b inhibition was insufficient to block TGF-beta induced EMT of NMUMG cells.Mir-99a and mir-99b over-expression in epithelial NMUMG cells resulted in increased proliferation, migration and fibronectin expression, while E-cadherin and ZO-1 expression were negatively regulated.In conclusion, we identified mir-99a and mir-99b as two novel modulators of TGF-beta pathway that alter SMAD3 phosphorylation, in turn altering cell migration and adhesion of mesenchymal NMUMG cells. The effect of mir-99a and mir-99b over expression on NMUMUG proliferation is dependent upon the epithelial or mesenchymal status of the cells. Our study suggests that mir-99a and mir-99b may function as modulators within a complex network of factors regulating TGF-beta induced breast epithelial to mesenchymal transition, as well as proliferation and migration of breast cancer cells, providing a possible target for future translationally oriented studies in this area. PMID- 22299048 TI - Renal tubular HIF-2alpha expression requires VHL inactivation and causes fibrosis and cysts. AB - The Hypoxia-inducible transcription Factor (HIF) represents an important adaptive mechanism under hypoxia, whereas sustained activation may also have deleterious effects. HIF activity is determined by the oxygen regulated alpha-subunits HIF 1alpha or HIF-2alpha. Both are regulated by oxygen dependent degradation, which is controlled by the tumor suppressor "von Hippel-Lindau" (VHL), the gatekeeper of renal tubular growth control. HIF appears to play a particular role for the kidney, where renal EPO production, organ preservation from ischemia-reperfusion injury and renal tumorigenesis are prominent examples. Whereas HIF-1alpha is inducible in physiological renal mouse, rat and human tubular epithelia, HIF 2alpha is never detected in these cells, in any species. In contrast, distinct early lesions of biallelic VHL inactivation in kidneys of the hereditary VHL syndrome show strong HIF-2alpha expression. Furthermore, knockout of VHL in the mouse tubular apparatus enables HIF-2alpha expression. Continuous transgenic expression of HIF-2alpha by the Ksp-Cadherin promotor leads to renal fibrosis and insufficiency, next to multiple renal cysts. In conclusion, VHL appears to specifically repress HIF-2alpha in renal epithelia. Unphysiological expression of HIF-2alpha in tubular epithelia has deleterious effects. Our data are compatible with dedifferentiation of renal epithelial cells by sustained HIF-2alpha expression. However, HIF-2alpha overexpression alone is insufficient to induce tumors. Thus, our data bear implications for renal tumorigenesis, epithelial differentiation and renal repair mechanisms. PMID- 22299049 TI - Identifying quantitative trait loci affecting resistance to congenital hypothyroidism in 129/SvJcl strain mice. AB - Tyrosylprotein sulfotransferase 2 (TPST2) is one of the enzymes responsible for tyrosine O-sulfation and catalyzes the sulfation of the specific tyrosine residue of thyroid stimulating hormone receptor (TSHR). Since this modification is indispensable for the activation of TSH signaling, a non-functional TPST2 mutation (Tpst2(grt)) in DW/J-grt mice leads to congenital hypothyroidism (CH) characterized by severe thyroid hypoplasia and dwarfism related to TSH hyporesponsiveness. Previous studies indicated that the genetic background of the 129(+Ter)/SvJcl (129) mouse strain ameliorates Tpst2(grt)-induced CH. To identify loci responsible for CH resistance in 129 mice, we performed quantitative trait locus (QTL) analysis using backcross progenies from susceptible DW/J and resistant 129 mice. We used the first principal component calculated from body weights at 5, 8 and 10 weeks as an indicator of CH, and QTL analysis mapped a major QTL showing a highly significant linkage to the distal portion of chromosome (Chr) 2; between D2Mit62 and D2Mit304, particularly close to D2Mit255. In addition, two male-specific QTLs showing statistically suggestive linkage were also detected on Chrs 4 and 18, respectively. All QTL alleles derived from the 129 strain increased resistance to growth retardation. There was also a positive correlation between recovery from thyroid hypoplasia and the presence of the 129 allele at D2Mit255 in male progenies. These results suggested that the major QTL on Chr 2 is involved in thyroid development. Moreover, since DW/J congenic strain mice carrying both a Tpst2(grt) mutation and 129 alleles in the major QTL show resistance to dwarfism and thyroid hypoplasia, we confirmed the presence of the resistant gene in this region, and that it is involved in thyroid development. Further genetical analysis should lead to identification of genes for CH tolerance and, from a better understanding of thyroid organogenesis and function, the subsequent development of new treatments for thyroid disorders. PMID- 22299050 TI - Developmentally regulated sphingolipid degradation in Leishmania major. AB - Leishmania parasites alternate between extracellular promastigotes in sandflies and intracellular amastigotes in mammals. These protozoans acquire sphingolipids (SLs) through de novo synthesis (to produce inositol phosphorylceramide) and salvage (to obtain sphingomyelin from the host). A single ISCL (Inositol phosphoSphingolipid phospholipase C-Like) enzyme is responsible for the degradation of both inositol phosphorylceramide (the IPC hydrolase or IPCase activity) and sphingomyelin (the SMase activity). Recent studies of a L. major ISCL-null mutant (iscl(-)) indicate that SL degradation is required for promastigote survival in stationary phase, especially under acidic pH. ISCL is also essential for L. major proliferation in mammals. To further understand the role of ISCL in Leishmania growth and virulence, we introduced a sole IPCase or a sole SMase into the iscl(-) mutant. Results showed that restoration of IPCase only complemented the acid resistance defect in iscl(-) promastigotes and improved their survival in macrophages, but failed to recover virulence in mice. In contrast, a sole SMase fully restored parasite infectivity in mice but was unable to reverse the promastigote defects in iscl(-). These findings suggest that SL degradation in Leishmania possesses separate roles in different stages: while the IPCase activity is important for promastigote survival and acid tolerance, the SMase activity is required for amastigote proliferation in mammals. Consistent with these findings, ISCL was preferentially expressed in stationary phase promastigotes and amastigotes. Together, our results indicate that SL degradation by Leishmania is critical for parasites to establish and sustain infection in the mammalian host. PMID- 22299051 TI - Grape seed proanthocyanidins inhibit the invasiveness of human HNSCC cells by targeting EGFR and reversing the epithelial-to-mesenchymal transition. AB - Head and neck squamous cell carcinoma (HNSCC) is responsible for approximately 20,000 deaths per year in the United States. Most of the deaths are due to the metastases. To develop more effective strategies for the prevention of metastasis of HNSCC cells, we have determined the effect of grape seed proanthocyanidins (GSPs) on the invasive potential of HNSCC cell and the mechanisms underlying these effects using OSC19 cells as an in vitro model. Using cell invasion assays, we established that treatment of the OSC19 cells with GSPs resulted in a dose dependent inhibition of cell invasion. EGFR is over-expressed in 90% of HNSCCs and the EGFR inhibitors, erlotinib and gefitinib, are being explored as therapies for this disease. We found that GSPs treatment reduced the levels of expression of EGFR in the OSC19 cells as well as reducing the activation of NF-kappaB/p65, a downstream target of EGFR, and the expression of NF-kappaB-responsive proteins. GSPs treatment also reduced the activity of ERK1/2, an upstream regulator of NF kappaB and treatment of the cells with caffeic acid phenethyl ester, an inhibitor of NF-kappaB, inhibited cell invasion. Overexpression of EGFR and high NF-kappaB activity play a key role in the epithelial-to-mesenchymal transition, which is of critical importance in the processes underlying metastasis, and we found treatment with GSPs enhanced the levels of epithelial (E-cadherin, cytokeratins and desmoglein-2) and reduced the levels of mesenchymal (vimentin, fibronectin, N cadherin and Slug) biomarkers in the OSC19 cells. These results indicate that GSPs have the ability to inhibit HNSCC cell invasion, and do so by targeting the expression of EGFR and activation of NF-kappaB as well as inhibiting the epithelial-to-mesenchymal transition. PMID- 22299052 TI - The polyamine inhibitor alpha-difluoromethylornithine modulates hippocampus dependent function after single and combined injuries. AB - Exposure to uncontrolled irradiation in a radiologic terrorism scenario, a natural disaster or a nuclear battlefield, will likely be concomitantly superimposed on other types of injury, such as trauma. In the central nervous system, radiation combined injury (RCI) involving irradiation and traumatic brain injury may have a multifaceted character. This may entail cellular and molecular changes that are associated with cognitive performance, including changes in neurogenesis and the expression of the plasticity-related immediate early gene Arc. Because traumatic stimuli initiate a characteristic early increase in polyamine metabolism, we hypothesized that treatment with the polyamine inhibitor alpha-difluoromethylornithine (DFMO) would reduce the adverse effects of single or combined injury on hippocampus structure and function. Hippocampal dependent cognitive impairments were quantified with the Morris water maze and showed that DFMO effectively reversed cognitive impairments after all injuries, particularly traumatic brain injury. Similar results were seen with respect to the expression of Arc protein, but not neurogenesis. Given that polyamines have been found to modulate inflammatory responses in the brain we also assessed the numbers of total and newly born activated microglia, and found reduced numbers of newly born cells. While the mechanisms responsible for the improvement in cognition after DFMO treatment are not yet clear, the present study provides new and compelling data regarding the potential use of DFMO as a potential countermeasure against the adverse effects of single or combined injury. PMID- 22299053 TI - Chikungunya virus infection of cell lines: analysis of the East, Central and South African lineage. AB - Chikungunya virus (CHIKV) is a re-emerging mosquito borne alphavirus that has caused large scale epidemics in the countries around the Indian Ocean, as well as leading to autochthonous transmission in some European countries. The transmission of the disease has been driven by the emergence of an African lineage of CHIKV with enhanced transmission and dissemination in Aedes mosquito hosts. Two main genotypes of this lineage have been circulating, characterized by the presence of a substitution of a valine for an alanine at position 226 of the E1 protein. The outbreak, numbering in millions of cases in the infected areas, has been associated with increasing numbers of cases with non-classical presentation including encephalitis and meningitis. This study sought to compare the original Ross strain with two isolates from the recent outbreak of chikungunya fever in respect of infectivity and the induction of apoptosis in eight mammalian cell lines and two insect cell lines, in addition to generating a comprehensive virus production profile for one of the newer isolates. Results showed that in mammalian cells there were few differences in either tropism or pathogenicity as assessed by induction of apoptosis with the exception of Hela cells were the recent valine isolate showed less infectivity. The Aedes albopictus C6/36 cell line was however significantly more permissive for both of the more recent isolates than the Ross strain. The results suggest that the increased infectivity seen in insect cells derives from an evolution of the CHIKV genome not solely associated with the E1:226 substitution. PMID- 22299054 TI - Non-host defense response in a novel Arabidopsis-Xanthomonas citri subsp. citri pathosystem. AB - Citrus canker, caused by Xanthomonas citri subsp. citri (Xcc), is one of the most destructive diseases of citrus. Progress of breeding citrus canker-resistant varieties is modest due to limited resistant germplasm resources and lack of candidate genes for genetic manipulation. The objective of this study is to establish a novel heterologous pathosystem between Xcc and the well-established model plant Arabidopsis thaliana for defense mechanism dissection and resistance gene identification. Our results indicate that Xcc bacteria neither grow nor decline in Arabidopsis, but induce multiple defense responses including callose deposition, reactive oxygen species and salicylic aicd (SA) production, and defense gene expression, indicating that Xcc activates non-host resistance in Arabidopsis. Moreover, Xcc-induced defense gene expression is suppressed or attenuated in several well-characterized SA signaling mutants including eds1, pad4, eds5, sid2, and npr1. Interestingly, resistance to Xcc is compromised only in eds1, pad4, and eds5, but not in sid2 and npr1. However, combining sid2 and npr1 in the sid2npr1 double mutant compromises resistance to Xcc, suggesting genetic interactions likely exist between SID2 and NPR1 in the non-host resistance against Xcc in Arabidopsis. These results demonstrate that the SA signaling pathway plays a critical role in regulating non-host defense against Xcc in Arabidopsis and suggest that the SA signaling pathway genes may hold great potential for breeding citrus canker-resistant varieties through modern gene transfer technology. PMID- 22299055 TI - Immunohistochemical profile for unknown primary adenocarcinoma. AB - BACKGROUND: Development of tailored treatment based on immunohistochemical profiles (IPs) of tumors for cancers of unknown primary is needed. METHODOLOGY/PRINCIPAL FINDINGS: We developed an algorithm based on primary known adenocarcinoma for testing sensitivity and specificity. Formalin-fixed paraffin embedded tissue samples from 71 patients of unfavorable subsets of unknown primary adenocarcinoma were obtained. We examined 15 molecular markers using the algorithm incorporating these IPs and classified the tumours into 9 subsets based on the primary tumour site. The sensitivity and specificity of this algorithm were 80.3% and 97.6%, respectively. Apparent primary sites were lung in 17 patients, digestive organs in 13, gynecological organs in 9, prostate in 7, liver or kidney in 6, breast in 4, urothelial organ in 2, biliary tract and pancreatic profile in none, and unclassified in 13. The response rate to chemotherapy was highest for the gynecological IPs. Patients with gynecological or lung cancer IPs had longer median progression-free survival than those with others: 11.2 months for gynecological IPs (p<0.001) and 6.8 months for lung IPs (p = 0.05). Lung, digestive, prostate, and gynecological profiles were associated with significantly longer median survival time than the other profiles. Multivariate analysis confirmed that the IPs were independent prognostic factors for survival. CONCLUSIONS/SIGNIFICANCE: The IPs identified in this study can be used to further stratify patient prognosis for unfavorable subsets of unknown primary adenocarcinoma. PMID- 22299056 TI - Distance and helical phase dependence of synergistic transcription activation in cis-regulatory module. AB - Deciphering of the spatial and stereospecific constraints on synergistic transcription activation mediated between activators bound to cis-regulatory elements is important for understanding gene regulation and remains largely unknown. It has been commonly believed that two activators will activate transcription most effectively when they are bound on the same face of DNA double helix and within a boundary distance from the transcription initiation complex attached to the TATA box. In this work, we studied the spatial and stereospecific constraints on activation by multiple copies of bound model activators using a series of engineered relative distances and stereospecific orientations. We observed that multiple copies of the activators GAL4-VP16 and ZEBRA bound to engineered promoters activated transcription more effectively when bound on opposite faces of the DNA double helix. This phenomenon was not affected by the spatial relationship between the proximal activator and initiation complex. To explain these results, we proposed the novel concentration field model, which posits the effective concentration of bound activators, and therefore the transcription activation potential, is affected by their stereospecific positioning. These results could be used to understand synergistic transcription activation anew and to aid the development of predictive models for the identification of cis-regulatory elements. PMID- 22299057 TI - Design and Implementation of Noble Metal Nanoparticle Cluster Arrays for Plasmon Enhanced Biosensing. AB - Nanoparticle Cluster Arrays (NCAs) are a class of electromagnetic materials that comprise chemically defined nanoparticles assembled into clusters of defined size in an extended deterministic arrangement. NCAs are fabricated through integration of chemically synthesized building blocks into predefined patterns using a hybrid top-down/bottom-up fabrication approach that overcomes some of the limitations of conventional top-down fabrication methods with regard to minimum available feature size and structural complexity. NCAs can sustain near-field interactions between nanoparticles within individual clusters as well as between entire neighboring clusters. The availability of near-field interactions on multiple length scales - together with the ability to further enhance the coupled plasmon modes through photonic modes in carefully designed array morphologies - leads to a multiscale cascade electromagnetic field enhancement throughout the array. This feature article introduces the design and fabrication fundamentals of NCAs and characterizes the electromagnetic coupling mechanisms in the arrays. Furthermore, it reviews how the optical properties of NCAs can be tuned through the size and shape of the nanoparticle building blocks and the geometry, size, and separation of the assembled clusters. NCAs have potential applications in many different areas; this feature article focuses on plasmon enhanced biosensing and surface enhanced Raman spectroscopy (SERS), in particular. PMID- 22299058 TI - Cells diversify transmembrane signaling through the controlled chaos of protein disorder. AB - Cell surface receptors function to transduce signals across the cell membrane leading to a variety of biologic responses. Structurally, these integral proteins can be classified into two main families, depending on whether extracellular ligand-binding and intracellular signaling domains are located on the same protein chain (single-chain receptors, SRs) or on separate subunits (multichain receptors, MRs). Since most MRs are immune receptors, they are all commonly referred to as multi-chain immune recognition receptors (MIRRs). Recent studies reveal that, in contrast to well-structured signaling domains of SRs, those of MIRRs represent intrinsically disordered regions, the regions that lack a well defined three-dimensional structure under physiological conditions. Why did nature separate recognition and signaling functions of MIRRs? Why for MIRRs did nature select to provide highly specific signaling through the chaos of protein disorder? What mechanisms could control this chaos in the process of transmembrane signal transduction to provide the specificity and diversity of the immune response? Here, I summarize recent findings that may not only shed light on these and other questions but also add significantly to our understanding of receptor signaling, a fundamental process that plays a critical role in health and disease. PMID- 22299059 TI - Adoptive immunotherapy of cancer: Gene transfer of T cell specificity. AB - Adoptive transfer of tumor-reactive T cells has emerged as a promising advance in tumor immunotherapy. Specifically, infusion of tumor-infiltrating lymphocytes has led to long-term objective clinical responses for patients with metastatic melanoma. Donor lymphocyte infusion is also an effective treatment of post transplant lymphoproliferative disease. However, adoptive T cell therapy has restrictions in the isolation and expansion of antigen-specific lymphocytes for a large group of patients. One approach to circumvent this limitation and extend adoptive immunotherapy to other cancer types is the genetic modification of T cells with antigen-specific receptors. In this article, we review strategies to redirect T cell specificity, including T cell receptor gene transfer and antibody receptor gene transfer. PMID- 22299060 TI - Visualization of Cell-Cell Interaction Contacts: Synapses and Kinapses. AB - T-cell activation requires interactions of T-cell antigen receptors (TCR) and peptides presented by major histocompatibility complex molecules (MHCp) in an adhesive junction between the T-cell and antigen-presenting cell (APC). Stable junctions with bull's eye supramolecular activation clusters (SMACs) have been defined as immunological synapses. The term synapse works in this case because it joins roots for "same" and "fasten," which could be translated as "fasten in the same place." These structures maintain T-cell-APC interaction and allow directed secretion. We have proposed that SMACs are not really clusters, but are analogous to higher order membrane-cytoskeleton zones involved in amoeboid locomotion including a substrate testing lamellipodium, an adhesive lamella and anti adhesive uropod. Since T-cells can also integrate signaling during locomotion over antigen presenting cells, it is important to consider adhesive junctions maintained as cells move past each other. This combination of movement (kine-) and fastening (-apse) can be described as a kinapse or moving junction. Synapses and kinapses operate in different stages of T-cell priming. Optimal effector functions may also depend upon cyclical use of synapses and kinapses. Visualization of these structures in vitro and in vivo presents many distinct challenges that will be discussed in this paper. PMID- 22299061 TI - Visualization of Protein Interactions in Living Cells. AB - Ligand binding to cell membrane receptors sets off a series of protein interactions that convey the nuances of ligand identity to the cell interior. The information may be encoded in conformational changes, the interaction kinetics and, in the case of multichain immunoreceptors, by chain rearrangements. The signals may be modulated by dynamic compartmentalization of the cell membrane, cellular architecture, motility, and activation-all of which are difficult to reconstitute for studies of receptor signaling in vitro. In this paper, we will discuss how protein interactions in general and receptor signaling in particular can be studied in living cells by different fluorescence imaging techniques. Particularly versatile are methods that exploit Forster resonance energy transfer (FRET), which is exquisitely sensitive to the nanometer-range proximity and orientation between fluorophores. Fluorescence correlation microscopy (FCM) can provide complementary information about the stoichiometry and diffusion kinetics of large complexes, while bimolecular fluorescence complementation (BiFC) and other complementation techniques can capture transient interactions. A continuing challenge is extracting from the imaging data the quantitative information that is necessary to verify different models of signal transduction. PMID- 22299062 TI - HCV: Written in our DNA. AB - An inspection of the sequence similarity between the hepatitis C virus (HCV) polyprotein and human proteins revealed a high level of peptide sharing, with a limited number of motifs unique to the virus (i.e., with no counterpart in the human proteome). Using pentapeptide matching, only 214 motifs out of a total of 3,007 (7.11%) identified HCV as nonself compared to the Homo sapiens proteome. However, this virus-versus-human phenetic difference disappeared at the genetic level. Indeed, a BLAST analysis of pentadecameric oligodeoxynucleotide sequences corresponding to the 214 pentapeptides unique to HCV revealed that almost all of them are present in the human genome, located in the non-coding strand, introns, and/or pseudogenes, thus being, as such, untranslatable. The present data warn against using DNA-based vaccines to fight HCV infection and emphasize peptide uniqueness as the molecular basis for designing effective anti-HCV immunotherapeutic approaches. PMID- 22299063 TI - Selfness-nonselfness in designing an anti-B19 erythrovirus vaccine. AB - Although B19 erythrovirus infection may be associated with severe clinical outcomes, especially in early infancy, pregnancy and in immunocompromised or hemolytic subjects, no vaccine is currently available. Using the concept that effective immune responses to an infectious agent may be restricted to the specific peptidome unique to that agent, we analyzed primary amino acid sequence of B19 erythrovirus, searching for peptide motifs to be used in vaccine formulations. Here, we identify and describe a set of unique viral peptides that may guarantee both high efficacy and practically no cross-reactive autoimmune responses in anti-B19 immunotherapeutic approaches. PMID- 22299064 TI - Cytokine gene expression in the skin and peripheral blood of atopic dermatitis patients and healthy individuals. AB - OBJECTIVES: Atopic dermatitis (AD) is an increasingly common, chronic, relapsing, inflammatory skin disease characterized by impaired epidermal barrier function and cutaneous inflammation. The prevalence of AD has steadily increased during the past few decades. The aim of this study was to comparatively investigate cytokine gene expression in the skin and peripheral blood of atopic dermatitis patients and healthy individuals. RESULTS: In the skin of patients with AD, a significant increase of the level of gene expression was observed for interleukin (IL)-2r (p < 0.0023), IL-5 (p = 0.002), IL-6 (p < 0.0023), IL-8 (p = 0.01), IL 12B (p < 0.0023), IL-10 (p < 0.0023), IL-23 (p = 0.002), IL-29 (p < 0.0023), and transforming growth factor beta (tGFbeta) (p < 0.0023) as compared to healthy individuals. In contrast, no difference between AD patients and healthy donors was detected with respect to cytokine gene expression in the peripheral blood. METHODS: Samples of skin and peripheral blood from 48 severe AD patients (SCORAD = 78.5 [57;89], IGA = 4.2 [3,9;4,7]) at the age of 17 to 45 years and 20 healthy donors aged from 19 to 32 years were analyzed for gene expression of cytokines using real-time reverse transcription polymerase chain reaction (RT-PCR). CONCLUSIONS: Activity of markers of chronic inflammation and Th1 immune response in severe AD, namely IL-2r, IL-8, IL-12B, IL-23, IL-29 and TGFbeta, as well as activity of anti-inflammatory IL-5 were predominant in the skin but not in the blood of AD patients. PMID- 22299066 TI - Magnetomotive optical coherence elastography for relating lung structure and function in Cystic Fibrosis. AB - Cystic fibrosis (CF) is a genetic defect in the cystic fibrosis transmembrane conductance regulator protein and is the most common life-limiting genetic condition affecting the Caucasian population. It is an autosomal recessive, monogenic inherited disorder characterized by failure of airway host defense against bacterial infection, which results in bronchiectasis, the breakdown of airway wall extracellular matrix (ECM). In this study, we show that the in vitro models consisting of human tracheo-bronchial-epithelial (hBE) cells grown on porous supports with embedded magnetic nanoparticles (MNPs) at an air-liquid interface are suitable for long term, non-invasive assessment of ECM remodeling using magnetomotive optical coherence elastography (MMOCE). The morphology of ex vivo CF and normal lung tissues using OCT and correlative study with histology is also examined. We also demonstrate a quantitative measure of normal and CF airway elasticity using MMOCE. The improved understanding of pathologic changes in CF lung structure and function and the novel method of longitudinal in vitro ECM assessment demonstrated in this study may lead to new in vivo imaging and elastography methods to monitor disease progression and treatment in cystic fibrosis. PMID- 22299065 TI - Children of mothers with borderline personality disorder: identifying parenting behaviors as potential targets for intervention. AB - Children of mothers with borderline personality disorder (BPD) should be considered a high-risk group given the wide array of poor psychosocial outcomes that have been found in these children. This article describes the parenting strategies that might explain the transmission of vulnerability from mothers with BPD to their offspring, from infancy through adolescence. We conclude that oscillations between extreme forms of hostile control and passive aloofness in their interactions with their children may be unique to mothers with BPD. We provide an overview of interventions that are currently recommended for mothers and family members with BPD, namely attachment therapy and psychoeducational approaches. On the basis of an integration of the empirical findings on parenting and child outcomes, as well as from the review of current approaches to intervention, we conclude with recommendations for treatment targets. We argue that mothers with BPD need psychoeducation regarding child development and recommended parenting practices and skills for providing consistent warmth and monitoring, including mindfulness-based parenting strategies. PMID- 22299067 TI - The organocatalytic three-step total synthesis of (+)-frondosin B. AB - The frondosins are a family of marine sesquiterpenes isolated from the sponge Dysidea frondosa that exhibit biological activities ranging from anti inflammatory properties to potential application in anticancer and HIV therapy. Herein, a concise enantioselective total synthesis of (+)-frondosin B is described which requires a total of three chemical steps. The enantioselective conjugate addition of a benzofuran-derived boronic acid to crotonaldehyde in the presence of an imidazolidinone organocatalyst builds the critical stereogenic center of frondosin B in the first operation, while the remaining two ring systems of this natural product are installed in the two subsequent steps. A combination of X-ray crystallographic data, deuterium labeling, and chemical correlation studies provides further evidence as to the correct absolute stereochemical assignment of (+)-frondosin B. PMID- 22299068 TI - Multiple sclerosis or neuromyelitis optica? Re-evaluating an 18th-century illness using 21st-century software. AB - In this paper we report the application of an extensive database of symptoms, signs, laboratory findings and illnesses, to the diagnosis of an historical figure. The medical diagnosis of Augustus d'Este (1794-1848) - widely held to be the first documented case of multiple sclerosis - is reviewed, using the detailed symptom diary, which he kept over many years, as clinical data. Some of the reported features prompted the competing claim that d'Este suffered from acute porphyria, which in turn was used in support of the hypothesis that his grandfather, King George III, also suffered from the disease. We find that multiple sclerosis is statistically the most likely diagnosis, with neuromyelitis optica a strong alternative possibility. The database did not support a diagnosis of any of the acute porphyrias. PMID- 22299069 TI - How influences on teenage smoking reflect gender and society in Mali, West Africa. AB - OBJECTIVES: To provide further understanding and discussion on the influences on smoking in young people in Mali. DESIGN: A generic qualitative methodological approach was used following Caelli's generic principles. Six focus group discussions were conducted with a total of 31 participants followed by two semi structured interviews. A reflexive account was kept to record development in the researcher's theoretical position SETTING: The setting was recreational areas of Bamako, capital city of Mali, West Africa. PARTICIPANTS: Participants aged 13-15 years were recruited opportunistically in a recreational area of Bamako. MAINOUTCOME MEASURES: To develop further understanding of the influences of teenage smoking in Mali, West Africa. RESULTS: FIVE MAIN CATEGORIES THAT EXPLAINED INFLUENCES ON YOUTH SMOKING EMERGED: knowledge and awareness of smoking; associations with smoking; influential people; key messages in Malian society; and access to tobacco. The results showed that influences were complex and interwoven, notable gender differences were revealed, and the role of elder members of the community proved decisive in participants' smoking experiences. Participants described vague knowledge of the impact on health of smoking and reported trying smoking from an early age. Often contact with smoking was through elders and being sent to buy and sometimes light cigarettes for them. Associations with smoking were influenced by gender with smoking more desirable for boys than girls. CONCLUSIONS: Any approach to preventing smoking initiation in young people requires an understanding of the social influences and pressures on young people. A tobacco control strategy is required to look at all areas of influence on smoking behaviours. Different needs should also account for the differing characteristics and perceptions of specific population groups. PMID- 22299070 TI - Is typing speed proportional to the severity of pain in keyboard workers with work-related upper limb disorder. AB - OBJECTIVES: To investigate if typing speed is proportional to the severity of pain in keyboard workers with work-related upper limb disorder (WRULD). DESIGN: Standardized functional typing test with participants scoring pain before and after typing; calculation of typing speed. PARTICIPANTS: Fifty-nine patients and six controls. SETTING: Tertiary hospital centre for hand and upper limb pain. MAIN OUTCOME MEASURES: Pain (VAS 0-10) and calculation of typing speed as words per minute. RESULTS: THREE SUBGROUPS OF PATIENTS WERE FOUND BASED ON THEIR TYPING SPEED: fast, slow and intermediate. Two-tailed student T-test with P level at 0.05 was used for evaluation. The typing speeds were significantly different between all three patient groups (P < 0.05). The typing speed was significantly faster in the fastest patient group than in the control group (P = 0.04) and the slow and middle groups (P = < 0.0001). The pain before typing was highest in the 'slow' group, in both hands but this difference was not statistically significant. CONCLUSION: Typing speed is not proportional to the severity of pain in keyboard workers with WRULD. Patients with statistically significant slower or faster typing speeds do not have statistically different levels of pain. PMID- 22299071 TI - Alternative diagnoses to chronic fatigue syndrome in referrals to a specialist service: service evaluation survey. AB - OBJECTIVE: To assess the accuracy of diagnoses made by referrers to a chronic fatigue syndrome (CFS) service. DESIGN: Retrospective service evaluation surveys of both rejected referral letters and medical case-notes after full clinical assessment. SETTING: A specialist CFS clinic in London, UK. PARTICIPANTS: In the first survey, we assessed rejected referral letters between March 2007 and September 2008. In the second survey, we ascertained the primary diagnosis made in case-notes of 250 consecutive new patients assessed between April 2007 and November 2008. MAIN OUTCOME MEASURES: Reasons for rejection of referrals and primary diagnosis in those assessed. RESULTS: In the first survey, 154 out of 418 referrals (37%) were rejected. Of these, 77 out of the available 127 referrals (61%) had a likely alternative diagnosis. In the second survey of clinically assessed patients, 107 (43%) had alternative medical/psychiatric diagnoses, while 137 out of 250 (54%) patients received a diagnosis of CFS. The commonest alternative medical diagnoses of those assessed were sleep disorders and the commonest alternative psychiatric diagnosis was depressive illness. Altogether 184 of 377 (49%) patients had alternative diagnoses to CFS. CONCLUSIONS: Half of all the referred patients to a specialist CFS clinic had alternative medical and psychiatric diagnoses. Specialist medical assessment for patients with unexplained, disabling, chronic fatigue needs to incorporate both medical and psychiatric assessments. PMID- 22299072 TI - Use of hydrogen peroxide in neurosurgery: case series of cardiovascular complications. AB - OBJECTIVES: Postoperative complications induced by hydrogen peroxide (H(2)O(2)) are described in the neurosurgical literature and mainly involve oxygen venous emboli, postoperative pneumocephalus; some of them even fatal. However, recently there are more and more published case reports for significant cardiac dysrhythmia related to the use of this chemical agent during routine neurosurgical interventions. DESIGN: Retrospective, two-centre study. SETTING: Retrospective review of clinical/radiological documentation (including preoperative medical history, operation report and intraoperative anesthesiology data charts). PARTICIPANTS: Patients scheduled for cranial neurosurgical interventions. MAIN OUTCOME MEASURES: Intraoperative occurrence of trigeminocardiac reflex (TCR), according the earlier defined by our group criteria, or other severe cardiovascular complications related to the intraoperative use of H(2)O(2). RESULTS: Five cases were included in the study fulfilling the strict inclusion/exclusion criteria. Two of the cases were recognized as intraoperative TCR, in the other three cases the cardiovascular effects were possibly due to TCR in one, mechanical stimulation of vital centre in anterior hypothalamus, brainstem, or either mechanical or thermal action of H(2)O(2). CONCLUSIONS: According to this two-centre study, we can give, for the first time, evidence that cardiovascular complications according to the intraoperative use of H(2)O(2) in neurosurgery are not rare with an incidence of 3%. Special reference is given to the occurrence of the TCR in this context. PMID- 22299073 TI - Patients with non-diagnostic hyperamylasaemia must be investigated and managed as per acute pancreatitis. AB - OBJECTIVES: The identification of hyperamylasaemia insufficient to confidently diagnose acute pancreatitis in patients with epigastric pain poses a clinical dilemma. The aim of this study was to identify a cohort of such patients and review their presentation, investigation and outcome. DESIGN: Patients admitted through the emergency surgical intake during a 12-month period with serum amylase levels of 100-400 IU/L were identified and case notes reviewed to confirm those presenting with upper abdominal pain. Subsequent radiological and biochemical investigations were recorded. PARTICIPANTS: A total of 25 patients with non diagnostic hyperamylasaemia. SETTING: Ward patients in a University Hospital. MAIN OUTCOME MEASURES: Amylase level, eventual diagnosis, drug history. RESULTS: Twenty-five patients were identified with a mean age of 46.7 years. The median serum amylase level was 230 IU/L (range 102-358 IU/L). Twenty-two patients underwent transabdominal ultrasound at presentation, with gallstones identified in nine cases. The remaining three had documented gallstones and were awaiting elective cholecystectomy. Of the 13 patients with no evidence of cholelithiasis, six were taking medications known to cause pancreatitis, seven patients underwent computed tomography (CT) scans that identified chronic pancreatitis in three, and were non-diagnostic in four cases. These four patients underwent endoscopic ultrasound (EUS) evaluation of the biliary tree identifying microlithiasis in one but no pathology in the remaining three cases. CONCLUSIONS: Patients with hyperamylasaemia not diagnostic of pancreatitis should be carefully investigated, as gallstones will be identified in at least 50%. An accurate drug history is also invaluable. PMID- 22299074 TI - Establishing a standard of care. PMID- 22299075 TI - Digitizing implant position locators on master casts: comparison of a noncontact scanner and a contact-probe scanner. AB - PURPOSE: Although several investigations of the fit of computer-aided design/computer-assisted manufactured implant restorations have been reported in the literature, very limited information is available on the accuracy of dental scanners for surface data acquisition. The objective of this research project was to investigate the accuracy and repeatability of a three-dimensional noncontact laser scanning system based on conoscopic holography recording the spatial orientation of an implant in vitro. MATERIALS AND METHODS: One master cast containing five nonparallel implant replicas with scan abutments (implant position locator [IPL], Nobel Biocare) was repeatedly digitized by two commercially available dental scanners and an industrial highprecision coordinate measuring machine as a reference. Repeated measurements of the center point and vector analysis were applied to determine the accuracy and repeatability of IPL orientation. The Wilcoxon signed rank test modified for equivalence was applied to determine whether the systems were equally accurate based on given threshold limits of 0.010, 0.005, and 0.001 mm. RESULTS: All between-system tests identified significant differences, although most differences were very small in absolute terms. Tests for equivalence based on difference windows were exploratorily significant for 0.010 and 0.005 mm. CONCLUSION: Conoscopic holography scan technology is a valid option to supplement dental touch-probe scanners for laboratory digitization of implant master casts. PMID- 22299076 TI - Influence of abutment height and surface roughness on in vitro retention of three luting agents. AB - PURPOSE: This study evaluated the effects of abutment height, airborne-particle abrasion, and type of cement on the tensile resistance to dislodgement of cement retained implant restorations. MATERIALS AND METHODS: Three groups of 12 standardized abutments each were prepared with different heights (4 mm, 5 mm, and 6 mm) using a milling machine. Crowns were cast in cobalt-chrome using the lost wax technique, airborne particle-abraded using 50-MUm aluminum oxide, and cleaned with acetone. Restorations were cemented using a noneugenol acrylic urethane cement, a resin-modified glass ionomer, or a zinc oxide-noneugenol cement. A 5-kg load was applied for 10 minutes. Samples were kept at 37 degrees C and 100% humidity overnight. A tensile force was applied to the crown using a testing machine at a crosshead speed of 5 mm/minute until failure occurred. Next, the abutments were airborne particle-abraded with 50-MUm aluminum oxide, and the cementation and testing procedures were repeated. The effects of cement, abutment height, and surface treatment were evaluated statistically. RESULTS: There were significant differences among the cements. The resin-modified glass ionomer provided the greatest retention in all the tested conditions, while the zinc oxide-noneugenol cement produced the lowest retention values. Significant differences were also detected between 4-mm and 6-mm abutments, with the 6-mm abutments being more retentive. No differences were found between 4-mm and 5-mm abutments or between 5-mm and 6-mm abutments. The effect of airborne-particle abrasion was also found to be significant. A maximum increase of 90 N in retention force was observed after airborne-particle abrasion for the 5-mm abutments cemented with the acrylic urethane cement. CONCLUSIONS: Cement, airborne-particle abrasion, and abutment height can significantly influence retention of implant-supported crowns. Different parameters, including those specific to the patient, should be considered in the selection of a luting agent. PMID- 22299077 TI - Screw loosening with interchangeable abutments in internally connected implants after cyclic loading. AB - PURPOSE: The purpose of this study was to observe and compare any loosening of screws attaching several interchangeable abutments to internally connected implants after cyclic loading. MATERIALS AND METHODS: Four different abutment groups mated with Straumann single-stage transmucosal implants (n = 7 each group) were assessed: Straumann solid abutment, Restore COC abutment, Neoplant solid abutment, and AVANA solid abutment. Each implant was fixed rigidly in a special holding jig. Abutments were tightened to 35 Ncm with a torque controller. A cyclic load of 150 N at a 30-degree angle to the long axis was applied to the implants for 1 million cycles. Prior to loading, Periotest values (PTVs) were measured. After cyclic loading, PTVs were measured and removal torque values (RTVs) of abutments were measured with a digital torque gauge. RESULTS: No mechanical failures were noted for the Straumann solid abutment or the Restore COC abutment. Six Neoplant abutment screws fractured (86%), and four implants fractured (57%) in the group restored with AVANA solid abutments. The RTVs of the Straumann solid abutment were significantly higher than those of the other abutments. The final mean PTV of the Straumann solid abutment was significantly lower than the final mean PTVs of the other abutments. The final mean PTV (4.76 +/- 5.58) was significantly higher than the initial mean PTV (-4.29 +/- 0.47). CONCLUSIONS: Although different abutments are interchangeable with each other, they possess different chemical compositions and physical characteristics. The use of an abutment and implant manufactured by the same company is recommended to prevent the loosening of the abutment screw. PMID- 22299078 TI - Relationship between subsinus bone height and bone volume requirements for dental implants: a human radiographic study. AB - PURPOSE: To analyze the vertical dimension of subsinus alveolar bone that is available for placement of endosseous implants. MATERIALS AND METHODS: Subsinus alveolar bone height (SBH) was determined via radiographs and categorized into three groups: Group A corresponded to SBH < 5 mm; group B SBH of 5 to 9 mm; and group C, SBH > 9 mm. Statistical analysis was carried out using the Wilcoxon paired test with the threshold for statistical significance set at P < .05. RESULTS: Five hundred eighty-three panoramic radiographs of edentulous maxillae were analyzed. In 96.9% of radiographs, the anterior border of the maxillary sinus was above the first premolar. Mean SBH values for canine, first premolar, second premolar, first molar, and second molar sites were 11.4 +/- 6.2 mm, 10.6 +/- 3.8 mm, 5.9 +/- 2.5 mm, 3.3 +/- 2.2 mm, and 4.5 +/- 2.4 mm, respectively. Representations of groups A, B, and C in the canine region were 14.3%, 21.4%, and 64.3%, respectively; in the first premolar region they were 8.3%, 22.3%, and 69.4%, respectively; in the second premolar region, these were 31.6%, 60.9%, and 7.5%, respectively; in first molar region, the values were 73.1%, 25.4%, and 1.5%, respectively; and in the second molar region they were 54.2%, 41.7%, and 4.1%, respectively. CONCLUSIONS: The mean SBH is the highest in the area of the anterior border of the sinus; it declines significantly toward the posterior maxilla, reaches its minimum in the area of the first molar, and increases again significantly in the second molar region. From a clinical point of view, the lateral window technique of sinus elevation remains the dominant augmentative procedure in the molar area, whereas in the premolar area, less invasive alternative methods may be more appropriate. PMID- 22299079 TI - The effect of changes in head position on enlargement of structures during panoramic radiography. AB - PURPOSE: Accuracy of panoramic radiographs is essential for distance measurements during implant planning, but it might be compromised by various factors. The aim of the present study was to evaluate the effect of vertical and horizontal head positioning on area-dependent enlargement ratios of digital panoramic radiography. MATERIALS AND METHODS: The mandible of a dry skull was marked with small steel globes. The skull was moved 1 to 4 degrees in 1-degree increments to the left and right and up and down. A series of 17 panoramic radiographs was obtained with the same digital radiographic device. For the rotated skull, horizontal and vertical distances, indicated by the steel globes, were compared to the distances with the ideal positioning of the skull. The results were analyzed statistically. RESULTS: Head positioning and angulation, anatomical site, and distance orientation influenced horizontal measurements. Enlargement ratios of horizontal distances of the right canine and first molar regions (skull rotation to the right 2 to 4 degrees) were significantly lower than those for the corresponding anatomical sites on the left side. Horizontal distance measurements of the different anatomical sites of the left and the right jaw did not differ significantly from each other when the skull was moved downward. When the skull was rotated upward, no significant differences were obtained for corresponding anatomical sites of the right and left arches. Enlargement ratios of vertical distances of different anatomical sites, as well as within the same anatomical site, were not significantly different from each other for the given skull rotations. CONCLUSIONS: Ideal head positioning for digital panoramic radiographs is mandatory to avoid improper enlargement ratios of horizontal distances, which can be important in implant dentistry. PMID- 22299080 TI - Effect of oral bacteria on the mechanical behavior of titanium dental implants. AB - PURPOSE: This study sought to determine whether the mechanical properties of titanium dental implants changed after exposure to bacteria. MATERIALS AND METHODS: Two strains of bacteria (Streptococcus sanguinis and Lactobacillus salivarius) were used in the study. The adhesive properties of the two strains were investigated as follows. Titanium implants were placed in bacteria broth, seeded with the two bacteria strains, and left in the broth for 1 or 3 months. Another group of titanium implants was immersed in artificial saliva at 37 degrees C for 3 months. Ten implants in each group were tested in 37 degrees C artificial saliva to evaluate their mechanical flexural strength and fatigue life. RESULTS: The bacterial cultures grew quickly on titanium surfaces. After 1 month of bacteria culture in vitro, the bacteria had produced corrosion pits on the titanium surfaces. After 3 months of bacterial culture, a 7% decrease in the flexural strength of the implant samples and a decrease of 15% in the number of cycles to failure by fatigue were seen versus implants not exposed to bacteria. CONCLUSIONS: These results demonstrate that, in physiologic conditions in vitro, bacteria have the capacity to produce a pitting corrosion phenomenon on exposed titanium surfaces, leading to a significant deterioration in the mechanical properties of the implant. It is therefore logical to conclude that bacteria may produce corrosion that reduces the useful life of dental implants. PMID- 22299081 TI - Trends in funding, internationalization, and types of study for original articles published in five implant-related journals between 2005 and 2009. AB - PURPOSE: The aims of this study were to evaluate the trends in funding, geographic origin, and study types of original articles in the dental implant literature and to investigate the relationships among these factors. MATERIALS AND METHODS: Articles published in Clinical Oral Implants Research, The International Journal of Oral and Maxillofacial Implants, Clinical Implant Dentistry and Related Research, Implant Dentistry, and Journal of Oral Implantology from 2005 to 2009 were reviewed. Nonoriginal articles were excluded. For each article included, extramural funding source, geographic origin, and study type were recorded. Descriptive and analytic analyses (alpha = .05), including a logistic regression analysis, and chi-square test were used where appropriate. RESULTS: Of a total of 2,085 articles published, 1,503 met the inclusion criteria. The most common source of funding was from industry (32.4%). The proportion of studies that reported funding increased significantly over time. Europe represented the highest percentage (55.8%) of published articles. Most of the articles reported on clinical studies (49.9%), followed by animal studies (25.9%). Articles from Asia and South America and animal and in vitro studies were significantly more likely to be funded. CONCLUSION: Almost half of the original dental implant articles were funded. The trend toward internationalization of authorship was evident. A strong association was observed between funding and geographic origin and between funding and study type. Most studies in North America and Europe were clinical studies and supported by industry, whereas a greater proportion of studies in Asia and South America were in vitro or animal studies funded through government resources. PMID- 22299082 TI - Effect of implant surface properties on peri-implant bone healing: implant stability and microcomputed tomographic analysis. AB - PURPOSE: The present study aimed to evaluate and compare two types of implants: grit-blasted and acidetched implants (SLActive) and nanometer-scale hydroxyapatite-modified implants (NanoTite). MATERIALS AND METHODS: Twenty-two SLActive and 22 NanoTite implants were inserted into the mandibles of 11 beagle dogs. The animals were divided into three groups according to healing time (group A, 2 weeks; group B, 4 weeks; group C, 8 weeks). Resonance frequency analysis (RFA) was performed immediately after implant placement and after 2, 4, and 8 weeks of healing. Two, 4, and 8 weeks after implantation, the animals were sacrificed and the amount of bone surrounding the implants was assessed using microcomputed tomography. RESULTS: For SLActive and NanoTite implants, the RFA values decreased after 2 weeks and increased after 4 and 8 weeks of healing. After 8 weeks, the mean RFA value for SLActive implants was significantly higher than the mean RFA value for NanoTite implants. For the different healing periods, no significant differences in bone volume were seen for SLActive and NanoTite implants. CONCLUSIONS: SLActive and NanoTite implants evoked a similar bone response after implantation for 2, 4, and 8 weeks in a nonsubmerged position in the mandibles of dogs. In addition, the data confirmed that RFA is a reliable and noninvasive method to determine dental implant stability and the bone formation process at the clinical level. PMID- 22299083 TI - Histomorphometric analysis following augmentation of the anterior atrophic maxilla with cancellous bone block allograft. AB - PURPOSE: Grafting with bone blocks may be required to restore the alveolar process in extremely atrophic maxillae prior to implant placement to ensure both function and esthetics. The present study was conducted to histologically and histomorphometrically evaluate the application of allograft cancellous bone blocks for the augmentation of the anterior atrophic maxilla. MATERIALS AND METHODS: Consecutive patients with severe atrophy in the anterior maxilla underwent augmentation with cancellous bone block allografts. Bony deficiencies of at least 3 mm horizontally and up to 3 mm vertically according to computed tomographic para-axial reconstructions served as inclusion criteria. After 6 months, implants were placed and a cylindric sample core from the graft area was collected. All specimens were prepared for histologic and histomorphometric examination. RESULTS: Forty patients were included in the study. Eighty-three implants were placed in bone that was augmented with 60 cancellous freeze-dried bone block allografts. The implant survival rate was 98.8%. Mean follow-up was 48 +/- 22 months (range, 14 to 82 months). The mean percentage of newly formed bone was 33% +/- 18%, that of the residual cancellous block allograft was 26% +/- 17%, and marrow and connective tissue comprised 41% +/- 2%. Statistically significant histomorphometric differences regarding newly formed bone and residual cancellous block allograft were found between younger (< 40 years) and older (>= 40 years) patients, respectively. Age did not appear to influence the percentage of marrow and connective tissue. CONCLUSIONS: Cancellous bone block allograft is biocompatible and osteoconductive, permitting new bone formation following augmentation of extremely atrophic anterior maxillae in a two-stage implant placement procedure. New bone formation was age-dependent. PMID- 22299084 TI - Endosseous arteries in the anterior mandible: literature review. AB - PURPOSE: The purpose of this literature review was to investigate the topography of endosseous blood vessels supplying the anterior mandible to prevent complications both during and after oral surgical procedures. MATERIAL AND METHODS: A comprehensive literature search of MEDLINE-PubMed was performed independently for articles describing the anatomical findings of endosseous blood vessels in the anterior part of the mandible. From about 31 related studies, 14 papers were selected based on specific selection criteria. These studies were related to radiologic findings and cadaver studies. RESULTS: There is significant debate concerning the blood vessels supplying the anterior part of the mandible. Hence, in the literature reviewed, no clear consensus was established. There are no reports of severe endosseous bleeding from the mandible during surgical procedures in the symphysis. Based on computed tomographic images, some papers presented an exact intraosseous path of the canals, as well as frequent blood vessel anastomosis in this region. Dissection studies confirmed the presence of sublingual blood vessels penetrating into the bone. CONCLUSIONS: The potential risk of bleeding upon perforation of vessels within the bone needs to be evaluated to avoid such complications. The management of intraoperative surgical problems is of significance. PMID- 22299085 TI - Injectable magnesium-enriched hydroxyapatite putty in peri-implant defects: a histomorphometric analysis in pigs. AB - PURPOSE: The purpose of this study was to evaluate the healing of an injectable mixture of nanoparticles of magnesium-enriched hydroxyapatite (mHA) in peri implant defects. MATERIALS AND METHODS: Thirty-two dental implants were placed in 16 tibiae of eight female Large White pigs. In each animal, four implant beds (two sites each tibia) with medial three-wall intrabony defects were prepared. Via random selection, one bone defect in each tibia was filled with injectable mHA putty (n = 16, test group), whereas the other defect was not filled (n = 16, control group). Two animals were sacrificed after 2 weeks, two after 4 weeks, two after 6 weeks, and two after 8 weeks. In all, 32 block section samples were obtained for histologic and histomorphometric analyses. RESULTS: The test group exhibited statistically significantly higher values for bone-to-implant contact (BIC) and lower amounts of connective tissue (CT) over time. The test group showed a remarkable increase in vital bone values between 6 and 8 weeks after implant placement. After 8 weeks, the injectable mHA was almost completely resorbed. CONCLUSIONS: Injectable mHA putty could be a useful and suitable bone grafting material in peri-implant defects. PMID- 22299086 TI - A systematic review of biologic and technical complications with fixed implant rehabilitations for edentulous patients. AB - PURPOSE: The purpose of this systematic review was to assess the incidence and types of biologic and technical complications associated with implant-supported fixed complete dental prostheses (IFCDPs) for edentulous patients. MATERIALS AND METHODS: An electronic MEDLINE/PubMED search was conducted to identify randomized controlled clinical trials and prospective cohort studies with IFCDPs for edentulous patients. Reports with at least 5 years of follow-up after prosthesis insertion were selected. Pooled data were analyzed statistically, and the cumulative complication rates were calculated by meta-analysis and regression. RESULTS: Of a total of 281 one-piece IFCDPs (mean exposure time of 9.5 years) and 653 complication events, the complication rate was estimated at 24.6% per 100 restoration-years. The cumulative rates of "prosthesis free of complications" after 5 and 10 years were 29.3% and 8.6%, respectively. The most common implantrelated biologic complication was peri-implant bone loss (> 2 mm), at rates of 20.1% after 5 years and 40.3% after 10 years. The most frequent implant related technical complication was screw fracture, yielding a 5-year complication rate of 10.4% and a 10-year rate of 20.8%. The most frequent prosthesis-related biologic complication was hypertrophy or hyperplasia of tissue around the IFCDPs (13.0% and 26.0% after 5 and 10 years, respectively). The most common prosthesis related technical complication reported with IFCDPs was chipping or fracture of the veneering material (33.3% at 5 years and 66.6% at 10 years). CONCLUSION: Biologic and technical complications after the placement of IFCDPs occur continuously over time as a result of fatigue and stress. These events may not lead to implant/prosthetic failures, but they are significant in relation to the amount of repair and maintenance needed, time, and cost to both the clinician and patient. PMID- 22299087 TI - Comparison of restoratively projected and surgically acceptable virtual implant position for mandibular overdentures. AB - PURPOSE: To compare differences between restoratively projected and surgically acceptable virtual implant positions at sites identified by cylindric radiopaque markers on diagnostic templates for implant-retained mandibular overdentures using cone beam computed tomography (CBCT). MATERIALS AND METHODS: A retrospective chart audit of a CBCT database identified 77 subjects who had been imaged to assess the residual alveolar ridge in the completely edentulous mandible prior to implant placement for mandibular overdentures. Individuals had been scanned with a diagnostic template using cylindric markers to identify the restoratively derived locations and trajectories for implants. Qualitative and quantitative differences between restoratively projected and surgically acceptable positions on transaxial CBCT images were recorded using implant planning software based on a standard implant. RESULTS: Only 6.4% of restoratively projected positions were within the criteria for surgically acceptable implant placement. However, most implant placement plans (77.9%) could be modified to fulfill surgically acceptable criteria. Of the projected implant positions, 15.7% were deemed inadvisable because of potential anatomical complications. Restoratively projected implant position was more likely to deviate buccally than lingually to the available residual alveolar ridge, as determined by CBCT. The mean angular deviation of the clinical prediction from ideal was 14.0 +/- 5.5 degrees, the mean platform translation was 2.1 +/- 1.3 mm, and the mean apex translation was 2.3 +/- 1.5 mm. The average residual alveolar ridge reduction required in the posterior segment was 3.9 +/- 2.5 mm. CONCLUSION: The restoratively projected trajectory for implant placement determined by visual inspection, diagnostic casts, and panoramic radiography deviated from the surgically acceptable location determined using CBCT data sets. PMID- 22299088 TI - In vivo comparison of two bone substitutes in the distal femur of the rabbit. AB - PURPOSE: This study aimed to microradiographically evaluate the healing of grafted defects using a surgically standardized model that was suitable for comparing the regenerative potential of different grafts. MATERIALS AND METHODS: Two different biomaterials, bovine porous bone mineral (BPBM) and nanohydroxyapatite (NHA), were used to fill defects produced in the distal epiphyses of 10 adult male rabbits for 2 and 4 months. Three rabbits were left untreated, without defects, as controls. Evaluations were performed on microradiographs of sections of polymethyl methacrylate-embedded rabbit epiphyses. The amounts of graft material and bone were evaluated by splitting the filled hole into three portions. RESULTS: A greater amount of BPBM granules were in contact with bone at both 2 and 4 months versus the NHA (statistically significant difference in the central portion of the defect), and a persistence of the BPBM over time was apparent. The amount of NHA decreased from the inner to the outer portion of the defect, particularly after 4 months. The bone amount increased from the inner to the outer portion, particularly for the NHA graft, which produced an early cortex. The amount of mineralized material reached about 80% in the BPBM and 40% to 60% in the NHA after 4 months. CONCLUSION: Both the analyzed biomaterials performed adequately for bone regeneration. The two biomaterials are probably suitable for grafting defects related to early cortical formation or spacemaintaining clinical requirements. PMID- 22299089 TI - Accuracy of a newly developed open-source system for dental implant planning. AB - PURPOSE: To evaluate the accuracy of a newly developed open-source system for three-dimensional dental implant planning and fully guided dental implant placement. MATERIALS AND METHODS: Forty-eight implant positions were planned for eight partially edentulous anatomical patient equivalent models with an open source implant planning system on the basis of cone beam computed tomography (CBCT) scans. The virtual software planning leads to an output of four different coordinates for each implant position; with these, surgical guides were manufactured using a coordinate-transfer apparatus. During the surgical simulation, drills and implants were fully guided as they were inserted by means of the harmonized components of the vendor's sleeve-in-sleeve system. After follow-up CBCT investigation and reference marker-based software registration, linear horizontal, vertical, and maximal 3D deviations, as well as angular deviations, between the virtual planning data and the surgical results were calculated. RESULTS: The mean three-dimensional deviation values for the final implant positions were 671 MUm (95% confidence interval [CI] 452 to 891 MUm) at the implant base and 808 MUm (95% CI 646 to 971 MUm) at the implant tip. Mean vertical deviations were 273 MUm (95% CI 200 to 345 MUm). Mean angular deviations of 1.9 degrees (95% CI 1.4 to 2.4 degrees) were measured. CONCLUSIONS: The open source implant planning system described in this study demonstrated a level of accuracy that is equal or superior to most descriptions of the literature on computer-aided implant dentistry, allows for predictable implant positioning, and has the potential to reduce postoperative impairment versus conventional implant insertion. PMID- 22299090 TI - Effect of the platform-switching technique on preservation of peri-implant marginal bone: a systematic review. AB - PURPOSE: The aim of this study was to systemically review the effect of platform switching on preserving implant marginal bone. MATERIALS AND METHODS: An electronic search (PubMed and MEDLINE databases) and a hand search of peer reviewed journals for English-language articles published before June 30th, 2010, were performed. The selected articles included randomized controlled trials (RCTs) and prospective comparative clinical trials with a minimal sample size of 10 subjects and 10 implants followed for at least 1 year after loading. The quality of included RCTs was also assessed. RESULTS: Nine studies met the inclusion criteria; three were prospective comparative studies and six were RCTs. All studies applied either standardized conventional or digital periapical radiographs for the assessment of bone levels. Seven of the nine included articles demonstrated that platform switching was effective in preserving marginal bone around implants. The longest follow-up among these studies was 5 years. CONCLUSIONS: Based on the current evidence, the use of abutments with a smaller diameter than their corresponding implant platforms seems to exert beneficial effects on peri-implant marginal bone. Some potential confounding factors, for example, the apicocoronal position of implants in relation to crestal bone, the presence of various implant microtextures, the degree of platform switch, and the reliability of examination methods, should be considered when interpreting the present results. PMID- 22299091 TI - Biocompatibility and biodegradation of a native porcine pericardium membrane: results of in vitro and in vivo examinations. AB - PURPOSE: The principle of guided tissue and bone regeneration has long been established for treating bone and periodontal defects. In addition to nonabsorbable barriers, various collagens have become accepted as membrane materials for separating the graft from soft tissue. However, collagen membranes differ significantly in their barrier function and biocompatibility. The objective of this pilot study was to examine, in vitro and in vivo, a novel native collagen membrane extracted from porcine pericardium. MATERIALS AND METHODS: The morphologic structure of two different native collagen membranes (Remotis, Thommen Medical; Bio-Gide, Geistlich Biomaterials) was examined using a scanning electron microscope. For biocompatibility testing, membranes were incubated with SaOs-2 osteoblastlike cells. After 2 hours, 3 days, and 7 days, proliferation of the cells on the membranes was determined. Evaluation of the biodegradation pattern was performed in a dog model with simultaneous bone augmentation with Bio-Oss (Geistlich Biomaterials) or Cerabone (Botiss Biomaterials) in the lateral anterior maxilla in eight animals with histologic examination after 4, 8, 12, and 24 weeks. RESULTS: An interconnective pore system was identifiable for Remotis, while Bio-Gide displayed a more fibrous structure. In vitro, Remotis showed considerable cell proliferation, which was significantly superior to that observed with Bio-Gide, especially after 7 days (2,910 +/- 1,273 and 707 +/- 706, respectively). In vivo, both membranes integrated into the surrounding tissue without any inflammatory reaction. Both membranes allowed early vascularization. However, considerable biodegradation was noted within 4 to 8 weeks with Bio-Gide, while Remotis resorbed generally within the first 8 to 12 week. Both membranes supported underlying bone formation. CONCLUSION: Both examined membranes indicate a high level of biocompatibility. Both are resorbed without inflammation within 8 weeks (Bio-Gide) or 12 weeks (Remotis). The compact interconnective pericardium collagen of Remotis may have stabilized the resorption process. PMID- 22299092 TI - Long-term neuromuscular status in overdenture and complete denture patients with severe mandibular atrophy. AB - PURPOSE: The long-term neuromuscular status of edentulous patients with severe mandibular atrophy who wore complete dentures (CDs) or implant-supported overdentures (ISOs) was investigated in the present study. MATERIALS AND METHODS: Eleven CD patients and 11 patients with ISOs supported by two implants took part in the study. All patients had used their dentures for more than a decade. All patients (average age, 76 years) suffered from severe mandibular atrophy, which was to be quantified using panoramic radiographs and computer software. Kinesiographic parameters such as opening and extension movements as well as opening and closing velocities were recorded by means of a sirognathograph during test food chewing on the left and right sides. Simultaneously, electromyographic recording of masseter and temporalis activities was performed using surface electrodes. RESULTS: The kinesiographic values obtained from ISO patients were higher than those for CD patients: 12.65 mm for vertical opening (CD, 11.79 mm) and 5.66 mm for horizontal extension (CD, 5.11 mm). Opening velocity values were 100.93 mm/s and 91.74 mm/s, respectively. Closing velocity of 78.16 mm/s in ISO patients was significantly different from that measured in CD patients (58.45 mm/s). With regard to electromyographic activities, the increase was significant for the masseter during chewing on the working side (ISO: 189.79 MUV, CD: 78.05 MUV) and on the nonworking side (ISO: 130.53 MUV, CD: 47.25 MUV). For the temporalis, values of 194.11 MUV and 119.02 MUV in the ISO and CD patients, respectively, were observed for working side chewing. Nonworking side values reached 155.48 MUV for ISO subjects and 78.35 MUV for CD subjects, which was significantly different. The degree of atrophy in both groups did not differ statistically. CONCLUSIONS: The use of two interforaminal implants with an overdenture can provide long-term neuromuscular benefits for edentulous patients. PMID- 22299093 TI - Stability and marginal bone loss with three types of early loaded implants during the first year after loading. AB - PURPOSE: To determine the change in stability of three different implant systems using resonance frequency analysis (RFA) and to correlate RFA measurements with factors related to implant design, length, and diameter, patient gender, and dental arch. Clinical and radiologic evaluations were performed up to 1 year after loading. MATERIALS AND METHODS: Three different types of implants from three different manufacturers were inserted in the posterior maxilla and mandible. RFA measurements were performed at implant placement and weekly up to 8 weeks postoperatively and were compared with respect to implant type, length, and diameter and dental arch. The implants were loaded after 8 weeks. All implants were examined radiographically at baseline and at 6 and 12 months. Plaque Index, Sulcus Bleeding Index, peri-implant probing depths, and marginal bone loss were recorded. Repeated-measurements analysis of variance, two-tailed mixed-model analysis of variance, the Least Significant Differences and Mann-Whitney U tests were used for statistical analyses. RESULTS: All the groups showed high stability values at all time points (above 71). There were statistically significant differences between groups at all time points except 1 and 2 weeks. Mandibular implants showed statistically higher stability values than maxillary implants. Wide implants showed statistically higher stability values than narrow implants. Mean marginal bone loss was 0.22 +/- 0.47 mm after 1 year. CONCLUSIONS: All three implant systems showed clinically acceptable stability values prior to early loading. The success rates and bone loss were similar to the values reported in the literature. PMID- 22299094 TI - Immediate provisionalization of 3.0-mm-diameter implants replacing single missing maxillary and mandibular incisors: 1-year prospective study. AB - PURPOSE: This 1-year prospective study evaluated the implant success rate and peri-implant tissue response of narrow (3.0 mm) implants that were immediately provisionalized at maxillary and mandibular incisor sites. MATERIALS AND METHODS: Immediate provisionalization of single 3.0-mm diameter implants was performed in patients who fulfilled the inclusion/exclusion criteria. Implant success, marginal bone level (MBL), marginal bone level change (MBLC), Periotest value (PTV), modified Plaque Index, modified Bleeding Index, and Papilla Index Score (PIS) were evaluated immediately after implant placement and at 3, 6, and 12 months after surgery. All surgical and prosthetic complications were recorded. The data were analyzed statistically at a significance level of alpha =.05. RESULTS: Seventeen implants were immediately provisionalized in 13 patients with missing maxillary lateral incisor(s) and/or mandibular incisor(s). The implant success rates at 1 year were 100% (17/17). The mean MBL values at 0, 3, 6, and 12 months were -0.03 +/- 0.06 mm, -0.28 +/- 0.35 mm, -0.28 +/- 0.32 mm, and -0.38 +/ 0.36 mm, respectively. The mean MBLC from 0 to 12 months was -0.35 +/- 0.35 mm. The mean PTV at 3 months (-2.65) was significantly lower than that at baseline ( 1.59). No significant differences in plaque or bleeding indices were observed over time. A slight but significant increase in PIS over time indicated that the implant papillae were stable and well maintained. All complications were prosthetically related (seven fractured provisionals, two debonded provisionals, three loosened provisional abutment screws) and occurred within the first 3 months after surgery. CONCLUSIONS: This 1-year prospective study showed a favorable implant success rate and peri-implant tissue response with immediately provisionalized 3.0-mm diameter implants replacing single missing maxillary and mandibular incisors. While prosthetic complications during the provisional phase were common, they were easily resolved without further consequences. PMID- 22299095 TI - Clinical and radiologic evaluation of 70 immediately loaded single implants in the maxillary esthetic zone: preliminary results after 1 year of functional loading. AB - PURPOSE: A key challenge in implant treatment in the esthetic zone is to provide patients with crowns and peri-implant mucosa that are in harmony with the adjacent teeth to restore both function and esthetics. The aim of the present study was to show the preliminary results of an immediate loading protocol in the maxillary esthetic zone that is designed to preserve the soft tissue. MATERIALS AND METHODS: Patients were treated with immediately loaded single-tooth implants (Seven, MIS). Implants were inserted in fresh postextraction sites or in single edentulous sites with clinically and radiologically healed bone. After 8 weeks of loading, the provisional crowns and abutments were modified as needed to enhance the esthetics of the gingival margins. Definitive restorations were delivered 4 to 6 months postoperatively. RESULTS: Seventy patients were treated; 25 implants were placed in fresh extraction sites, and the remaining 45 implants were inserted in healed single edentulous sites. All implants were stable, and radiographs showed complete osseointegration after 1 year of functional loading. CONCLUSIONS: The present study shows promising results for immediate loading of single implants. All implant sites fulfilled success criteria in terms of function and esthetics, and particularly promising results were seen following additional adjustments of the provisional restorations to preserve interdental papillae. PMID- 22299096 TI - Stability measurements of craniofacial implants by means of resonance frequency analysis: 1-year clinical pilot study. AB - PURPOSE: The purpose of this pilot study was to apply resonance frequency analysis (RFA) to measure the clinical stability of craniofacial implants and compare the RFA measurements over a 12-month period. MATERIALS AND METHODS: Patients with auricular or orbital defects were treated with prostheses retained by two or three implants. After healing periods of 3 months for auricular implants and 6 months for orbital implants, prostheses were fabricated. RFA measurements were performed immediately after implant placement, at abutment connection, and at 6 and 12 months. All stability measurements were repeated three times for each implant, and the mean value was used for analyses. For measurements performed after prosthesis delivery, connecting bars and abutments were removed prior to RFA. The stability of both types of implants was compared at different time intervals. RESULTS: Fifty-four implants were placed in 10 patients with auricular defects (26 implants) and 10 patients with orbital defects (28 implants). All auricular implants survived, and four orbital implants in four different patients failed. For auricular implants, statistically significant differences in stability values were noted between implant placement, abutment connection, and 6 months; there was no significant difference between 6 and 12 months. For orbital implants, no significant differences were found between implant placement and abutment connection, a significant increase was observed at 6 months, and no significant difference was seen between 6 and 12 months. No significant differences were found for auricular versus orbital implants between placement and abutment connection, but auricular implants showed significantly higher stability values than orbital implants at 6 and 12 months. CONCLUSIONS: The stability of surviving auricular and orbital implants increased with time according to RFA. Prior to failure, the failed implants showed RFA values that were below the mean. PMID- 22299097 TI - A retrospective analysis of immediately placed implants in 418 sites exhibiting periapical pathology: results and clinical considerations. AB - PURPOSE: While immediate implant placement has demonstrated a high degree of clinical success, questions remain about whether immediate placement of implants into sites demonstrating periapical pathology will result in treatment outcomes equivalent to those attained when implants are placed into sites that do not demonstrate periapical pathology. MATERIALS AND METHODS: A retrospective study was carried out of patients who presented with periapical pathology and were treated with tooth extraction, defect debridement, and immediate implant placement between 1994 and 2008. All immediately placed implants were followed for a minimum of 24 months after restoration. Implant survival was assessed with the Albrektsson et al criteria and using measurements from the osseous crest to the most coronal extent of the rough surface of the implant on the midbuccal aspect of the implant. A classification system for periapical lesion morphology is also proposed. RESULTS: Four hundred eighteen implants were placed. They were followed for a mean of 67.3 months. Five implants were either lost or demonstrated progressive bone loss beyond acceptable levels, resulting in a cumulative survival rate of 97.8%. CONCLUSIONS: Implant placement at the time of extraction of teeth demonstrating periapical pathology will result in implant survival rates comparable to those of implants placed immediately into sites without periapical pathology. PMID- 22299098 TI - A retrospective study of the risk factors for ridge expansion with self-tapping osteotomes in dental implant surgery. AB - PURPOSE: To analyze the risk factors associated with the survival of self threading implants placed with the ridge expansion technique using self-tapping osteotomes after at least 24 months. MATERIALS AND METHODS: This retrospective study followed patients for at least 2 years in whom implants had been inserted by means of the ridge expansion technique. The patient was taken as the unit of analysis, and the loss of any implant as a result of mobility at any time during the follow-up period was considered as a failure. A number of patient variables were recorded: sociodemographic (age/sex), anatomical (bone quantity/quality, expansion zone), infection history (prior antibiotic therapy for active infection), prosthodontic (type of provisional prosthesis and type of definitive rehabilitation), and surgical (number of surgical stages, the use of biomaterials or atraumatic maxillary sinus elevation). Risk factors were expressed as values of relative risk (RR) and the odds ratio. RESULTS: Seventy-four patients (157 implants) were followed over a mean period of 38.8 +/- 7.7 months. Most patients (91.9%) did not lose any implants, and failures occurred mainly after implant loading (5.4%). Sociodemographic factors (sex and age) were not associated with a significant risk of implant failure. However, the existence of previous local infection (RR = 34.0), the use of an immediate fixed provisional prosthesis (RR = 15.0), and type D3 bone (RR = 5.1) were seen to be the main risk factors involved in this technique for the period assessed. CONCLUSIONS: The risk of failure when implants are placed using self-tapping osteotomes was highest in patients who had active local infection; immediate provisionalization and less dense bone were also associated with additional risk of failure. PMID- 22299099 TI - Bony window repositioning without using a barrier membrane in the lateral approach for maxillary sinus bone grafts: clinical and radiologic results at 6 months. AB - PURPOSE: There has been considerable controversy about the placement of barrier membranes over osteotomy and graft sites in sinus bone grafts via the lateral window approach. Particularly when the sinus membrane remains intact, clinicians should consider the benefits and costs of a barrier membrane. This article presents clinical and radiologic findings following repositioning of a detached bony window without a barrier membrane in the lateral approach for maxillary sinus bone grafts. MATERIALS AND METHODS: After a complete 360-degree osteotomy on the lateral maxillary wall, a bony window was outfractured and separated from the sinus membrane by gentle elevation. After the sinus membrane was confirmed to be intact, grafting was carried out and the bony window was repositioned over the graft material without rigid fixation or a barrier membrane. Clinical and radiologic examinations were performed 6 months postoperative. The relationships between the patterns of gap bone healing, number of implants, time of implant placement (simultaneous with grafting or staged), and thickness of the lateral sinus wall were analyzed. The Fisher exact test and Spearman nonparametric correlation coefficient were employed for statistical evaluation. RESULTS: All 23 included patients experienced no complications. Overall external cortical healing and bone regeneration in the gap between the repositioned window and the lateral wall of the sinus were satisfactory. No significant differences in the patterns of gap bone healing were found, with respect to the number of implants placed or time of implant placement. As the lateral sinus wall was thinner, gap bone healing was better. To date, no implants have failed. CONCLUSION: A detached bony window that is repositioned on graft material might function as a barrier membrane in the lateral approach for maxillary sinus bone grafts. PMID- 22299100 TI - Implant-supported first molar restorations: correlation of finite element analysis with clinical outcomes. AB - PURPOSE: This study aimed to evaluate the effect of the placement of wide diameter implants on bone stress concentrations and marginal bone loss in the first molar region. Study hypotheses held that increasing implant diameter would decrease peri-implant bone stress levels, but that statistically significant reductions in clinical bone loss would either (1) not be observed for any implant diameter or (2) be observed only for the widest implant diameter. MATERIALS AND METHODS: Three-dimensional finite element analysis (3D FEA) was used to analyze the relationship between implant diameter and peri-implant bone thickness, cortical bone thickness, occlusal load direction, and percentage of boneto implant contact on bone stress levels in the first molar region. A retrospective review of patient records was also conducted in three private practices to assess clinical outcomes and bone level changes around one implant design in three diameters (3.7, 4.7, and 6.0 mm) placed in first molar locations. Categorical variable summaries and comparisons of 3D FEA and clinical findings were made using the FREQ procedure, t test procedures (Student t tests, folded F tests, Satterthwaite t tests), and the NONPAR1WAY procedure (Wilcoxon nonparametric test). RESULTS: Cumulative implant success was 98.4% and survival was 98% after a mean of 49.2 months. Although increasing implant diameter always reduced peri implant stress concentrations in 3D FEA experiments, clinically, only 6.0-mm implants exhibited a statistically significant reduction in bone loss (0 mm) as compared to 3.7-mm and 4.7-mm implants. CONCLUSION: Only 6.0-mm implants were effective in reducing marginal bone loss in the first molar region. 3D FEA results supported previous clinical findings that maintaining approximately 1.8 mm of buccal plate thickness can help reduce bone stress concentrations and preserve buccal bone height. A history of periodontitis may adversely affect long term marginal bone stability. PMID- 22299101 TI - The importance of knowledge and the benefits of interdisciplinary treatment. PMID- 22299102 TI - Treatment planning challenge 4: dental and facial asymmetry--whether and on what to operate. PMID- 22299103 TI - In vitro evaluation of fluoride release of orthodontic bonding adhesives. AB - AIM: To assess the fluoride release from adhesives used for bonding in orthodontics. METHODS: Six bonding agents were evaluated: five adhesives (Biofix, Fill Magic Orthodontic, EagleBond, Orthobond, and Transbond XT) and one resin reinforced glass-ionomer cement (Fuji Ortho LC), the latter serving as a control. Ten samples of each adhesive were stored in containers with 5 mL of deionized distilled water at 37 degrees C. Fluoride release was measured with an ion specific electrode. Readings were taken periodically for a total of 33 days. On day 28, all samples were immersed in a 0.221% sodium fluoride solution for 5 minutes to assess their recharge potential. Descriptive statistics were calculated for the fluoride release rates of each material. ANOVA with multiple comparisons and the Kruskal-Wallis tests (P < .05) were used to assess differences between the groups. RESULTS: All adhesives released significant amounts of fluoride (P < .05). During the first day, Biofix released the highest amount of fluoride, followed by Fuji Ortho LC, which also showed the highest fluoride release from day 7 to day 33. The fluoride release from Biofix and Fuji Ortho LC decreased by the third day to 40% of its original value. All other adhesives maintained their fluoride release with only small fluctuations. CONCLUSION: All the materials released significant amounts of fluoride, with Biofix having the highest release in the first 3 days and Fuji Ortho LC over the total length of the experiment. PMID- 22299104 TI - Agenesis of maxillary lateral incisors: a global overview of the clinical problem. AB - The agenesis of maxillary lateral incisors is a common developmental anomaly and represents a clinical problem impairing dental esthetics and function from a very young age. Several dental specialties deal with the management of this clinical problem because a multidisciplinary approach can cover the complete dental needs of patients with dental agenesis. There is controversy, however, about whether missing lateral incisor spaces should be orthodontically opened or closed using permanent canines to replace the missing teeth. The article presents a review of the existing literature about the prevalence, etiology, diagnostic evaluation, and treatment strategy of maxillary lateral incisor agenesis. Also, this article aims to present the key determinants leading to selection of space opening or closure and to report professional judgments and layperson perception concerning the available treatment alternatives. The English-language literature associated with this topic was searched via PubMed. The articles retrieved were then reviewed with an attempt to fulfill the aims of this review. Maxillary lateral incisors are one of the most common congenitally missing teeth, and to date, the origin of their agenesis has not been completely identified. Prompt diagnosis and careful evaluation of treatment determinants through a multidisciplinary approach are essential for the proper management of clinical problems. Each of the available means of rehabilitation has its own advantages, disadvantages, indications, and limitations. The configuration of the treatment plan should be devoid of clinician biases, whereas patients' realistic expectations should be taken into account. PMID- 22299105 TI - Evaluation of the power arm in bringing about bodily movement using finite element analysis. AB - AIM: To evaluate the effectiveness of the power arm in bringing about bodily movement and to determine the ideal length and location of the power arm. METHODS: A geometric model of the maxillary right canine was constructed and subsequently converted to a finite element model. Material property data were represented, boundary conditions were defined, and force was applied. Different situations were simulated in which a power arm of varying vertical lengths were attached at different locations on the tooth--namely, the incisal, middle, and cervical thirds. RESULTS: The amount of bodily movement is maximum when the force is delivered directly at the cervical third. It decreases at the middle third and is least when attached at incisal third. The varying lengths of the power arm for a particular site of attachment does not bring about any change in the movement. CONCLUSION: The attachment of the power arm at the cervical third brought about maximum bodily movement, followed by the middle and incisal thirds. Variations in length of the power arm at different sites of attachment did not bring any change in the outcome. Thus, the point of attachment is critical in bringing about bodily movement. PMID- 22299106 TI - Does the design of self-ligating brackets show different behavior in terms of friction? AB - AIM: This in vitro study evaluated the friction generated by aligned stainless steel conventional brackets, self-ligating Damon MX brackets, Time3 brackets, Vision LP brackets, and low-friction Slide ligatures coupled with various stainless steel, nickel-titanium (Ni-Ti), and beta-titanium (TMA) archwires. METHODS: All brackets had a 0.022-inch slot; the orthodontic archwires were 0.014 inch Ni-Ti, 0.016-inch Ni-Ti, 0.014 x 0.025-inch Ni-Ti, 0.018 x 0.025-inch Ni-Ti, 0.017 x 0.025-inch TMA, 0.019 x 0.025-inch stainless steel, and 0.019 x 0.025 inch Ni-Ti. Each bracket-archwire combination was tested 10 times. RESULTS: Coupled with 0.014-inch Ni-Ti and 0.016-inch Ni-Ti archwire, conventional brackets generated the greatest friction, while Damon MX and Vision LP brackets generated the lowest (P < .05). No significant difference was observed between Time3 brackets and Slide ligatures. Coupled with all the rectangular archwires, Victory Series brackets, Slide ligatures, and Vision LP self-ligating brackets generated significantly lower friction than Time3 and Damon MX self-ligating brackets (P < .05). CONCLUSION: These findings suggest that self-ligating brackets are a great family of brackets that, in vitro, can generate different levels of friction when coupled with thin, thick, rectangular, or round archwires. Clinical conclusions based on our results are not possible, due to the limitations of the experimental conditions. PMID- 22299107 TI - Speech defect and orthodontics: a contemporary review. AB - In conjunction with the lips, tongue, and oropharynx, the teeth play an important role in the articulation of consonants via airflow obstruction and modification. Therefore, along with these articulators, any orthodontic therapy that changes their position may play a role in speech disorders. This paper examines the relevant studies and discusses the difficulties of scientific investigation in this area. The ability of patients to adapt their speech to compensate for most handicapping occlusion and facial deformities is recognized, but the mechanism for this adaptation remains incompletely understood. The overall conclusion is that while certain malocclusions show a relationship with speech defects, this does not appear to correlate with the severity of the condition. There is no direct cause-and-effect relationship. Similarly, no guarantees of improvement can be given to patients undergoing orthodontic or orthognathic correction of malocclusion. PMID- 22299108 TI - Comparison of two imaging programs in predicting the soft tissue changes with mandibular advancement surgery. AB - Establishing common objectives and expectations concerning the outcome of proposed surgical orthodontic therapy is a crucial part of the treatment planning process, which has been greatly simplified by imaging software. The purpose of this study was to investigate the reliability of two surgical imaging programs- Dolphin Imaging 10 and Vistadent OC--in simulating the actual outcome of mandibular advancement surgery by using a visual analog scale (VAS) judged by a panel of orthodontists, oral surgeons, and laypersons. The predictions were also analyzed with soft tissue cephalometric evaluation. The results of the study showed that in predicting the surgical outcome evaluated by the VAS, both programs received a mean rating of fair. One was marginally superior for the overall assessment among all three panelist groups. Region-wise, rating indicated the lower lip region to be the least accurate, and the submental region received the highest scores. The soft tissue cephalometric parameters showed minimal differences except for the lower lip parameters. Thus, Dolphin Imaging 10 and Vistadent OC are reliable in predicting mandibular advancement surgical outcomes with inaccuracies chiefly in the lower lip region. PMID- 22299109 TI - Anterior dental alignment and smile: perception and sensations in a sample of 8- to 10-year-old children and their parents. AB - AIM: To describe the perception and sensations that dental alignment and smile determine in a sample of 180 children aged between 8 and 10 years, to assess whether there is a general trend in the classification of smiles, and to understand the influence of background attractiveness and sexual traits on the judgment of smile in the sample of children and 150 parents. METHODS: We employed visual media showing a smile in four different arrangements (ideal incisal occlusion [N], median diastema [D], incisal crowding [A], and protruding incisors [P), in both a dynamic and static way, with and without background attractiveness. RESULTS: Trends were found among responses to the four classes of videos and photographs: The boy's smile gained a higher score than the girl's smile. In both the boy and girl presentations, there was an important preference to the following sequence of smiles: N, D, A, and P. Furthermore, the girl photographs showed no relevant difference between A and D. CONCLUSION: This study showed that there are no different perceptions and sensations due to the variation of dental alignment. There is a general trend in the classification of smiles according to dental alignment. Background attractiveness and sexual traits influenced the judgment of smile. PMID- 22299110 TI - Double impact: intrusion of two mandibular molars using an SAS--a case report. AB - The size of the envelope of tooth movements using fixed mechanotherapy has been increased with the use of temporary anchorage devices (TADs). Orthodontic mini implants, a form of TADs, have been successfully used for achieving a variety of tooth movements, such as bodily retraction, extrusion, protraction, and even intrusion of maxillary molars. However, the use of orthodontic mini-implants for intruding mandibular molars is questionable due to anatomical constraints. Skeletal anchorage systems (SASs), another form of TADs, overcome these limitations to give promising results for mandibular molar intrusion. The following case report shows the use of unilateral SAS for intruding two mandibular molars and extruding a maxillary molar of the same side to establish a stable occlusal plane. The amount of intrusion achieved in relation to mandibular molars was evaluated by comparing panoramic images. The mandibular left first and second molars were intruded by approximately 1.6 and 2.5 mm, respectively, in relation to the occlusal plane. PMID- 22299111 TI - A segmented appliance for space closure followed by Invisalign and fixed appliances. AB - This case report describes the use of a segmented appliance for space closure prior to using Invisalign. The maxillary right canine was retracted into the extracted first premolar space with a sectional wire from the first molar to the canine with no visible brackets in the incisor region. The advantage of this technique is the ability to achieve better root and rotational control during space closure with a fixed appliance that also has limited visibility. A maxillary fixed appliance was used to refine the esthetics in the maxillary arch due to the limitations of the Invisalign appliance in achieving rotational and vertical movements. PMID- 22299112 TI - Mini-implant-supported sliding jig. AB - Maximum anchorage situations require appropriate anchorage control from the very beginning. This includes control of anchorage in the anteroposterior as well as vertical directions. The requirement is more critical in patients with vertical growth patterns. Loss of anchorage in such situations requires recovery mechanics that will not tax the anchor teeth in any direction while maximizing efficiency. This article describes the use of a mini-implant-supported sliding jig in one such case where unilateral anchor loss in the maxillary arch was observed. A modified sliding jig was supported with Class II elastics stretched from a mini implant placed in the mandible. With little patient compliance, the mini-implant was used to distalize the maxillary molar to regain the lost space and achieve ideal results in the most efficient way. PMID- 22299113 TI - Crimpable double tubes for segmental retraction. AB - When a T-loop is used in segmental mechanics, it is generally attached posteriorly to an auxiliary tube in the first molars and anteriorly to a crimpable cross tube or a Burstone canine bracket. This article illustrates the use of a crimpable tube with a 90-degree bend on the base wire to secure a T-loop in segmental retraction. Both of these approaches allow a T-loop to be reactivated in a simple manner without undesirable changes in the system of forces, which could happen if the T-loop is skewed posteriorly. PMID- 22299114 TI - Mastery: Generating power and high performance. PMID- 22299115 TI - A crooked path to straightening teeth. PMID- 22299116 TI - Ethics in dentistry and Konigsberg. PMID- 22299117 TI - Template-guided flapless implant insertion and prosthetic rehabilitation with telescopic crowns in a patient with treated generalized aggressive periodontitis: a case report. AB - Implant therapy offers a wide range of possibilities in prosthetics. Especially for completely edentulous patients with early tooth loss due to periodontitis, implant therapy is an option to regain a comfortable, esthetic dental rehabilitation. Several studies have indicated that osseointegrated implants can be placed successfully in periodontally compromised patients but with lower survival and success rates than in uncompromised patients. This case report describes a patient that received periodontal therapy for generalized aggressive periodontitis and achieved prosthetic rehabilitation 16 years later with telescopic crowns by means of template-guided flapless implant insertion. In particular, in patients with a history of periodontitis in which bone loss makes implant planning more complicated and in whom wound healing might be compromised, the approach presented in this paper describes a method that is predictable and minimally traumatic. PMID- 22299118 TI - Multiple idiopathic cervical resorption: a diagnostic dilemma. AB - Multiple idiopathic cervical resorption is an uncommon condition, the etiology of which remains unknown. The case of a 36-year-old woman with idiopathic resorption in the cervical areas of multiple teeth is presented. Her medical history was noncontributory, but her dental history was valuable in reaching a diagnosis. Hematologic and endocrinal investigations were unremarkable, but a computed tomography scan revealed relevant information. The progression of the lesion and involvement of multiple teeth without any pattern or chronology are challenges faced when diagnosing and treating this condition. PMID- 22299119 TI - Tilted implants to support a maxillary removable dental prosthesis: a case report. AB - The placement of implants in a tilted position may provide a viable treatment modality, especially for patients with atrophic maxillae. The treatment steps and procedures for a maxillary implant-supported removable dental prosthesis, as well as a mandibular telescopic crown-retained removable dental prosthesis, are described. The concept of tilted implants via 3D planning and flapless surgery is presented. The final outcome facilitated improvement in the patient's satisfaction and comfort, as well as long-term stability of the implants and prosthesis. In addition, there was a reduction in cost by avoiding augmentation procedures. PMID- 22299120 TI - A systematic approach to deep caries removal end points: the peripheral seal concept in adhesive dentistry. AB - The objective of this article is to present evidence-based protocols for the diagnosis and treatment of deep caries lesions in vital teeth. These protocols combine caries-detecting dye with anatomical and histologic knowledge to arrive at ideal caries removal end points for adhesive restorations. DIAGNOdent laser fluorescence technology can also be used to confirm these end points. These ideal caries removal end points generate a peripheral seal zone that can support long term biomimetic restorations. A review of the published literature since 1980 on caries, caries diagnosis, and caries treatments and their relationships to adhesive bonding techniques was carried out. Combining anatomical measurements and pathologic and histologic knowledge with caries-detecting dye and DIAGNOdent laser fluorescence technologies can produce ideal caries removal end points for adhesive dentistry without exposing vital pulps. PMID- 22299121 TI - Preoperative oral nonsteroidal anti-inflammatory drugs for the success of the inferior alveolar nerve block in irreversible pulpitis treatment: a systematic review and meta-analysis based on randomized controlled trials. AB - OBJECTIVE: To assess the effect and safety of pre-emptive oral nonsteroidal anti inflammatory drugs (NSAIDs) for the success of inferior alveolar nerve block (IANB) in irreversible pulpitis treatment. METHOD AND MATERIALS: Medline (via OVID, 1948 to July 2011), Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2011), EMBASE (via OVID, 1984 to July 2011), Chinese BioMedical Literature Database (1978 to July 2011), China National Knowledge Infrastructure (1994 to July 2011), and WHO International Clinical Trials Registry Platform were searched electronically. In addition, relevant journals as well as reference lists of included studies were hand searched for randomized clinical trials comparing the effect or safety of NSAIDs in irreversible pulpitis treatment. Risk of bias assessment with the Cochrane collaboration tool and data extraction were independently performed by two reviewers. Meta-analysis was delivered with RevMan 5.1. RESULTS: Seven studies were included. Six of them had low risk of bias, and one had an unclear risk of bias. A dosage of 600 to 800 mg of ibuprofen showed a significant effect in increasing the success rate of IANB (relative risk [RR], 1.52; 95% confidence interval [CI], 1.17 to 1.98; P = .002), and the results were moderately reliable. A dosage of 75 mg of indomethacin had a significant effect compared to a placebo (RR, 1.94; 95% CI, 1.22 to 3.06; P = .005), as did 8 mg of lornoxicam (RR, 2.80; 95% CI, 1.59 to 4.93; P = .0004) and 50 mg of diclofenac potassium (RR, 2.40; 95% CI, 1.34 to 4.31; P = .003). Other NSAIDs such as ketorolac, ibuprofen and acetaminophen together, and acetaminophen alone showed no statistical significance compared to the placebo. No serious adverse events were reported. CONCLUSION: The clinical evidence suggests that pre emptive oral NSAIDs might have a good effect and are safe in increasing the success rate of IANB, but more studies are necessary to confirm such outcomes. PMID- 22299122 TI - Fluoride release from newly marketed fluoride varnishes. AB - OBJECTIVE: New fluoride varnishes have been marketed that reportedly release more fluoride (Enamel Pro) or release fluoride more slowly (Vanish XT). The purpose of this study was to compare the amount and rate of fluoride release of new fluoride varnishes with other traditional fluoride varnishes. METHOD AND MATERIALS: Extracted molars were cut into block sections. The enamel surfaces of the sections were painted with Enamel Pro, Duraphat, Vanish, or Vanish XT fluoride varnishes. One group was not treated and served as a negative control. The tooth sections were immersed in artificial saliva. The concentration of fluoride in parts per million was measured after the first 30 minutes, daily for the first week, and weekly until the level was below the limit of detection. Fluoride release was plotted over time. Cumulative fluoride release and rate of release (slope) were analyzed using one-way ANOVA/Tukey (alpha = .05). RESULTS: Enamel Pro had the greatest cumulative fluoride release. There was no significant difference between Duraphat and Vanish. Vanish XT had the lowest cumulative fluoride release. The rate of fluoride release from 1 week to limit of detection was Enamel Pro > Vanish > Duraphat > Vanish XT. CONCLUSION: The two newly marketed fluoride varnishes (Enamel Pro and Vanish XT) had significantly different fluoride release from the two conventional fluoride varnishes (Duraphat and Vanish). PMID- 22299123 TI - Methamphetamine abuse and oral health: a pilot study of "meth mouth". AB - Abuse of methamphetamine (meth), a potent central nervous system stimulant, has been associated with significant dental disease. Current descriptions of "meth mouth" are limited in their scope and fail to illuminate the potential pathogenic mechanisms of meth for oral disease. The purpose of this pilot study was to characterize the oral health of subjects with a history of meth abuse as compared to nonabusing control subjects. A total of 28 meth abusers and 16 control subjects were enrolled. Interviews and surveys regarding meth abuse, dental history, oral hygiene, and diet were collected. A comprehensive oral cavity examination including salivary characterization was completed. We observed significantly higher rates of decayed surfaces, missing teeth, tooth wear, plaque, and calculus among meth abusers. No significant difference in salivary flow rates were noted, yet results showed significant trends for lower pH and decreased buffering capacity. These findings suggest that salivary quality may play a more important role in meth mouth than previously considered. Salivary analysis may be useful when managing a dental patient with history of methamphetamine abuse. PMID- 22299124 TI - The effect of NitrAdine on the Candida levels of maxillary removable appliances. AB - OBJECTIVE: Candida colonization is a consequence of orthodontic treatment and can lead to oral candidosis as a complication of maxillary removable appliance treatment. During orthodontic treatment, it is important to minimize colonization to prevent active infection that could consequently interfere with treatment. Hygiene is the most important factor in managing colonization; in this study, the efficacy of NitrAdine to reduce Candida was tested. METHOD AND MATERIALS: A randomized, double-blind, placebo-controlled trial was performed. Ninety-two patients 11 to 14 years of age were recruited at the Children's and the University Dental Clinics at Mater Dei Hospital, Tal-Qroqq, Msida, Malta. Forty four patients used the product with NitrAdine, while 48 patients used a placebo. Sampling employing the imprint technique was performed before and after the product was used. Brilliance Candida agar was used for cultures and identification. Further identification was performed using Auxacolor 2 when required. RESULTS: The control group had a statistically significant increase in Candida during treatment, while the experimental group had a nonstatistically significant decrease. CONCLUSION: It was concluded that NitrAdine may reduce the Candida burden in maxillary removable appliances. Larger sample sizes are needed to achieve statistical significance. PMID- 22299125 TI - No association between A actinomycetemcomitans or P gingivalis and chronic or aggressive periodontitis diagnosis. AB - OBJECTIVES: Only a few studies have attempted to detect differences in microbiologic profiles of patients with chronic periodontitis (CP) and aggressive periodontitis (AgP). The aim of this analysis was to assess if clinical diagnosis or other subject factors showed association with the presence of Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in a cohort of periodontitis patients. METHOD AND MATERIALS: Statistical analysis for association between bacterial detection and clinical diagnosis was performed on a total of 267 consecutive periodontitis cases diagnosed with either CP (n = 183) or AgP (n = 84). All subjects had microbiologic samples collected from the four deepest pockets and analyzed by nested polymerase chain reaction. RESULTS: A actinomycetemcomitans was detected in 54% and 48% of CP and AgP subjects, respectively. A slightly higher detection of P gingivalis was found in CP (67% ) compared with AgP (52%) cases. The detection of P gingivalis was associated with older age (P = .002), less disease severity (P = .015), and IL6-1480 genotypes (P = .026), while A actinomycetemcomitans was associated with IL6-1480 genotypes (P = .001). CONCLUSION: Detection of known periodontopathogenic bacteria is not able to discriminate different forms of periodontitis. PMID- 22299126 TI - Clinical evaluation of the association of noncarious cervical lesions, parafunctional habits, and TMD diagnosis. AB - OBJECTIVE: To verify a potential association between the presence of noncarious cervical lesions, parafunctional habits, and temporomandibular disorder (TMD) diagnosis. METHOD AND MATERIALS: Sample-size calculation provided a value of 130 participants with a confidence level of 95% and an error margin of 5%. A population of 132 volunteers (30 men: mean age, 23.7 +/- 3.05 years; 102 women: mean age, 24.9 +/- 5.86 years) underwent an oral examination and was interviewed by a trained dentist. The following parameters were registered: personal details, TMD diagnosis, parafunctional habits, and noncarious cervical lesion presence. The population was then divided into a noncarious cervical lesion group and a control group and subjected to the t test, chi-square test, Fisher exact test, and Spearman correlation (alpha = .05). RESULTS: Noncarious cervical lesions were present in 39% of the population, with the largest concentrations found in the maxillary premolars (32%). The data showed a significant association between noncarious cervical lesion presence, tooth clenching (P = .03), and nail biting (P = .02), as well as a relation with TMD diagnosis (Fonseca Index [P = .01] and Research Diagnostic Criteria for TMD (RDC/TMD) [P = .004] ). In the noncarious cervical lesion group, direct rank correlation was found between maxillary premolars and clenching (P = .03), mandibular canines and nail biting (P = .05), and mandibular incisors and parafunctional habits without dental contacts (P = .02). CONCLUSION: Parafunctional habits and TMD presence should be taken into account in the diagnosis and treatment plan of noncarious cervical lesions. PMID- 22299127 TI - Oral and systemic manifestations of mucopolysaccharidosis type VI: a report of seven cases. AB - Mucopolysaccharidosis (MPS) is a group of rare metabolic diseases characterized by intralysosomal accumulation of glycosaminoglycans. MPS type VI or Maroteaux Lamy syndrome is an autosomal-recessive syndrome caused by mutations in the lysosomal enzyme arylsulfatase B. A defect in the gene leads to accumulation of nondegraded mucopolysaccharides, resulting in severe cellular dysfunction with multisystem expression. The oral manifestations of MPS VI are not well described in the literature. This paper presents a series of seven patients with MPS VI, with the description of the general clinical manifestations and focus on the still rarely studied oral manifestations of the syndrome. Among them were high palate, open bite, impacted and/or included teeth, thickening of the pericoronal follicle, and changes in the temporomandibular joint. PMID- 22299129 TI - Efficient synthesis of carbazoles via PtCl2-catalyzed RT cyclization of 1-(indol 2-yl)-2,3-allenols: scope and mechanism. AB - A detailed study on the scope of the efficient PtCl(2)-catalyzed synthesis of carbazoles from 1-(indol-2-yl)-2,3-allenols is described. Through isotopic labeling experiments, it is confirmed that the reaction proceeds through a unique metal carbene intermediate, which undergoes subsequent highly selective 1,2 hydrogen migration to afford carbazoles. The reaction shows wide scope and allows the introduction of a variety of different substituents at different positions on the carbazole due to the substituent-loading capability of both indole and the allene moiety. PMID- 22299130 TI - A non-aqueous solid phase extraction method for alkaloid enrichment and its application in the determination of hyoscyamine and scopolamine. AB - A non-aqueous solid phase extraction (SPE) method utilizing silica based strong cation exchange (SCX) was developed and optimized for the enrichment of alkaloids. In this method, silica based SCX SPE columns were used for the elimination of non-alkaloid compounds and the preconcentration of alkaloids from the extracts. Mass spectrometry was employed to analyze the alkaloid-enriched fraction, and results showed that the SPE method developed in this study was effective for the removal of non-alkaloids. Then, this pretreatment method was combined with high performance liquid chromatography for the quantification of scopolamine and hyoscyamine from Scopolia tangutica Maxim. The recoveries of scopolamine and (-)-hyoscyamine were 98.51% and 91.12%, respectively. Relative standard deviation values were 1.4% for scopolamine and 1.6% for (-)-hyoscyamine. The linearity was good in the 0.01-0.8 mg mL(-1) range for hyoscyamine and 0.01 0.4 mg mL(-1) range for scopolamine. PMID- 22299131 TI - Paired pulse voltammetry for differentiating complex analytes. AB - Although fast-scan cyclic voltammetry (FSCV) has contributed to important advances in neuroscience research, the technique is encumbered by significant analytical challenges. Confounding factors such as pH change and transient effects at the microelectrode surface make it difficult to discern the analytes represented by complex voltammograms. Here we introduce paired-pulse voltammetry (PPV), that mitigates the confounding factors and simplifies the analytical task. PPV consists of a selected binary waveform with a specific time gap between each of its two comprising pulses, such that each binary wave is repeated, while holding the electrode at a negative potential between the waves. This allows two simultaneous yet very different voltammograms (primary and secondary) to be obtained, each corresponding to the two pulses in the binary waveform. PPV was evaluated in the flow cell to characterize three different analytes, (dopamine, adenosine, and pH changes). The peak oxidation current decreased by approximately 50%, 80%, and 4% for dopamine, adenosine, and pH, in the secondary voltammogram compared with the primary voltammogram, respectively. Thus, the influence of pH changes could be virtually eliminated using the difference between the primary and secondary voltammograms in the PPV technique, which discriminates analytes on the basis of their adsorption characteristics to the carbon fiber electrode. These results demonstrate that PPV can be effectively used for differentiating complex analytes. PMID- 22299132 TI - Large outbreak of suspected botulism in a dairy herd in northern England. PMID- 22299133 TI - Botulinum toxin for the lower urinary tract. AB - Botulinum toxins (BoNTs) are known for their ability to potently and selectively modulate neurotransmission for successful long-term treatment of muscle hypercontractility. Recent studies suggest that BoNT has effects on modulation of sensory processing, inflammation and glandular function. Urologists and urogynaecologists have become interested in the potential application of BoNTs in patients with lower urinary tract symptoms, including detrusor and sphincter overactivity, bladder hypersensitivity, interstitial cystitis/painful bladder symptoms and benign prostatic hyperplasia. We review the biological action of BoNT in bladder and prostate, and present the techniques and results of the clinical studies with BoNT in the lower urinary tract. PMID- 22299134 TI - Recent advances in clay/polymer nanocomposites. PMID- 22299135 TI - Tunable ferrites as environmentally friendly materials for energy-efficient processes. PMID- 22299136 TI - The iron oxides strike back: from biomedical applications to energy storage devices and photoelectrochemical water splitting. PMID- 22299137 TI - The role of nocturia in the quality of life of men with lower urinary tract symptoms. AB - OBJECTIVES: To determine the role of treatment-associated improvement in nocturia in health-related quality of life (HRQL) in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia, and secondarily to confirm the role of nocturia in HRQL at baseline and to compare the effects of watchful waiting, transurethral microwave treatment (TUMT) and transurethral resection of the prostate (TURP) to those of alpha1-adrenoceptor antagonists (alpha-blockers) on nocturia. PATIENTS AND METHODS: We retrospectively analysed using multiple regression a large single-centre database of patients receiving routine care for treatment-associated alterations of symptoms and HRQL (assessed at baseline, 2611 men) and 6-12 months after initiation of treatment (1258 men). RESULTS: Among the symptoms assessed using the International Prostate Symptom Score, nocturia (together with urgency and weak stream) had the strongest correlation with HRQL at baseline and after treatment. Watchful waiting, alpha blockers, TUMT and TURP reduced nocturia episodes by a mean (sd) of 7 (53)%, 17 (40)%, 32 (47)% and 75 (23)%, respectively. The treatment-associated improvements in nocturia (together with those of weak stream) had the strongest association with those of HRQL. CONCLUSIONS: We conclude that among all LUTS assessed in the IPSS, nocturia has one of the strongest associations with HRQL, and that treatment-associated improvements in nocturia contribute considerably to overall improvements in HRQL. PMID- 22299138 TI - Supported graphene from natural resources: easy preparation and applications. PMID- 22299139 TI - Strain balanced epitaxial stacks of quantum dots and quantum posts. PMID- 22299140 TI - Progress in bionanocomposite and bioinspired foams. PMID- 22299141 TI - Tailoring interface structure in highly strained YSZ/STO heterostructures. PMID- 22299142 TI - Immobilized biocatalysts: novel approaches and tools for binding enzymes to supports. PMID- 22299143 TI - Towards inorganic porous materials by design: looking for new architectures. PMID- 22299144 TI - Operando spectroscopy: the knowledge bridge to assessing structure-performance relationships in catalyst nanoparticles. PMID- 22299145 TI - Interphases in graphene polymer-based nanocomposites: achievements and challenges. PMID- 22299147 TI - A reflection of the truth. By Caveman. PMID- 22299146 TI - Coordination polymers for nanoelectronics. PMID- 22299148 TI - Optical and electro-optical materials prepared by the sol-gel method. PMID- 22299149 TI - Progress in modeling graphene: the novel features of this material. PMID- 22299150 TI - Re: Evaluation of different modes of combined therapy in children with monosymptomatic nocturnal enuresis. PMID- 22299151 TI - Academy news. PMID- 22299152 TI - [Fight against malaria with genetically modified mosquitoes]. PMID- 22299153 TI - [Fight against human papillomavirus - vaccinate or lotion?]. PMID- 22299154 TI - [History of beta-sympathomimetics: From shock to drug design]. PMID- 22299155 TI - [The path to effect and side effect: pharmacology of beta-sympathomimetics]. PMID- 22299156 TI - Levothyroxine and sevelamer: listen to the patient. PMID- 22299157 TI - [Dosage forms of beta-sympathomimetics: dosage forms, formulations and deposition characteristics]. PMID- 22299158 TI - [Physico-chemical compatibility: beta-sympathomimetics and other drugs for aerosol inhalation treatment]. PMID- 22299159 TI - [Significance in therapy: beta-sympathomimetics in bronchial asthma]. PMID- 22299160 TI - [Use in special patient groups: beta-sympathomimetics in children and pregnant women]. PMID- 22299161 TI - [Success in the elucidation of receptor structure: medicinal chemistry of beta (2)-agonists]. PMID- 22299162 TI - [The Burning Bush - rare and highly flammable]. PMID- 22299163 TI - Retraction. Bisphosphonates promote jaw osteonecrosis through facilitating bacterial colonisation. [Med. Hypotheses 77 (2011) 214-215]. PMID- 22299164 TI - Characterization of the type of breathing disorder (obstructive vs central) may be of utmost importance. PMID- 22299165 TI - Recommending how the pulse duration or tilt should be programmed to reach optimum thresholds. PMID- 22299166 TI - Erratum to retraction notice to "Quantitative role of p42/44 and p38 in the production and regulation of cytokines TNF-alpha, IL-1beta and IL-12 by murine peritoneal macrophages in vitro by concanavalin A" [Cytokine 2007;37:62-70]. PMID- 22299167 TI - Nanosubstrates to illustrate differential adhesion mechanisms to fibronectin and vitronectin. PMID- 22299168 TI - Nanoporous titanium substrates for osteogenesis. PMID- 22299169 TI - Influence of local ligand density on formation of focal adhesions on nano- and micro-nanostructured surfaces. PMID- 22299170 TI - Nanoscale titanium surface treatments for marrow progenitor culture. PMID- 22299171 TI - Topography as a tool to facilitate endocytosis. PMID- 22299172 TI - [How much amount of socioeconomic loss is caused by digestive diseases?]. PMID- 22299173 TI - [A case of rectal carcinoid tumor with cystic degeneration]. PMID- 22299175 TI - Prepayment review pilot project recently launched by CMS. AB - The Centers for Medicare and Medicaid Services (CMS) has launched a three-year Medicare prepayment review demonstration project in 11 states. The prepayment reviews focus on high cost procedures with a high error rate. The Recovery Auditors (RAs) will perform the reviews. If the project is successful, CMS is likely to require prepayment reviews for all Medicare claims. Case managers should determine the payer mix and volume for targeted procedures and ensure that the documentation meets medical necessity criteria. PMID- 22299176 TI - Be prepared: Medicare auditors increase scrutiny. AB - The Centers for Medicare and Medicaid Services (CMS) is pushing its auditors to be more aggressive in reviewing hospital claims. CMS has set targets for how many claims the auditors should review. Auditors are encouraged to use extrapolation for denials when they find a pattern of erroneous claims. CMS has approved more than 570 diagnosis related group (DRGs) for medical necessity review. PMID- 22299177 TI - Discharge planning is CMS' focus. AB - The Centers for Medicare and Medicaid Services (CMS) has announced its intention to add three new questions about discharge planning to the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey in 2012. Case managers should make sure that patients have a choice of options for the next level of care. Make sure there are beds available and then give the patients a list of appropriate provides from which to choose. CAHPS scores are increasing in importance as CMS moves to value-based purchasing. PMID- 22299178 TI - ED navigators prevent unnecessary admissions. AB - RN Navigators in the emergency department at Montefiore Medical Center work with social workers to prevent unnecessary admissions. Program targets the homeless and patients with tenuous living situations. CMs work with the emergency department staff to identify patients who don't meet admission criteria but can't be safely discharged. The hospital collaborates with a local housing assistance agency which sends a van to transport appropriate patients to a shelter. PMID- 22299179 TI - Visits keep frail elderly out of hospital. AB - An interdisciplinary team from Boston University's Geriatric Service provides home visits for frail elderly patients who are homebound. The home care team includes a nurse case manager and a board-certified geriatrician. Physicians visit the patients every two or three months. Case managers visit as needed. Case managers use creativity to come up with ways to keep the elderly at home, including providing pest control, air conditioners, or chair lifts. The program coordinates care across sites of care, including a geriatric outpatient clinic, nursing homes, and an inpatient geriatric service, as well as the home visits. PMID- 22299180 TI - Project reviews admissions up front. AB - Covenant Health System is conducting a pilot project in which utilization managers review all patients admitted to the hospital and work with the physician to determine bed status. The team works in a centrally located access center from 6 a.m. to midnight and reviews cases admitted overnight each morning. The program allows emergency department case managers to concentrate on patients who do not meet criteria, and the unit case managers concentrate on care coordination. The team facilitates conference calls between the admitting physician and the physician transferring a patient from another hospital. PMID- 22299181 TI - [Haiti, still hard times]. PMID- 22299182 TI - A noteworthy effort. PMID- 22299192 TI - Social comparison and subjective well-being: does the health of others matter? AB - The importance of social comparison in shaping individual utility has been widely documented by subjective well-being literature. So far, income and unemployment have been the main dimensions considered in social comparison. This paper aims to investigate whether subjective well-being is influenced by inter-personal comparison with respect to health. Thus, we study the effects of the health of others and relative health hypotheses on two measures of subjective well-being: happiness and subjective health. Using data from the Italian Health Conditions survey, we show that a high incidence of chronic conditions and disability among reference groups negatively affects both happiness and subjective health. Such effects are stronger among people in the same condition. These results, robust to different econometric specifications and estimation techniques, suggest the presence of some sympathy in individual preferences with respect to health and reveal that other people's health status serves as a benchmark to assess one's own health condition. PMID- 22299193 TI - The end of destitution: evidence from urban British working households 1904-37. AB - We estimate the reduction, almost to elimination, of absolute poverty among working households in urban Britain between 1904 and 1937. We exploit two recently-digitized data sets. The paper presents a statistical generalization, to working families in the whole of urban Britain, of the poverty decline found in the town studies by, amongst other, Bowley and Rowntree. We offer corroborative evidence and perform a simulated decomposition of the poverty reduction into its proximate causes. The two most important causes were the rise, 1904-37, of about 30% in real wages on the one hand and the reduction of one-third in the number of people in the average household over the same period. Between them, these two changes imply a near doubling of the income per capita of an average household supported by a worker on the average wage. We conclude with a discussion of deeper causes. PMID- 22299194 TI - Spaces for counter-narratives: the phenomenology of reclamation. PMID- 22299195 TI - Caught in the crossfire: women's internationalism and the YWCA child labor campaign in Shanghai, 1921-1925. PMID- 22299196 TI - Marie Rozette and her world: class, ethnicity, gender, and race in late eighteenth- and early nineteenth-century Mauritius. AB - In 1790, Marie Rozette, a freedwoman of Indian origin on Mauritius, executed a series of notarial acts which revealed that she possessed a small fortune in cash assets as well as slaves and substantial landed property in one of the island's rural districts. The life of this former slave between 1776, when she first appears in the archival record, and her death in 1804 provides a vantage point from which to gain a subaltern perspective on aspects of Mascarene social and economic history, as well as developments in the wider Indian Ocean world during the late eighteenth and early nineteenth centuries. Marie Rozette's life history challenges the notion that free persons of color in Mauritius were little more than an "unappropriated" people, and invites us to consider how supposedly marginalized individuals were able to cross various socio-economic and cultural boundaries. More specifically, her life affords an opportunity to consider the ways in which class, ethnicity, and gender, as well as race, interacted to create a distinctive Creole society in Mauritius, the nature and dynamics of which bear directly on our knowledge and understanding of the free colored experience elsewhere in the European colonial slave plantation world. PMID- 22299197 TI - The "other" side of labor reform: accounts of incarceration and resistance in the Straits Settlements penal system, 1825-1873. AB - The rhetoric surrounding the transportation of prisoners to the Straits Settlements and the reformative capacity of the penal labor regime assumed a uniform subject, an impoverished criminal, who could be disciplined and accordingly civilized through labor. Stamford Raffles, as lieutenant governor of Benkulen, believed that upon realizing the advantages of the new colony, criminals would willingly become settlers. These two colonial prerogatives of labor and population categorized transportees into laboring classes where their exploitation supposedly brought mutual benefit. The colonized was collectively homogenized as a class of laborers and evidence to the contrary, of politically challenging and resistant individuals was suppressed. This paper focuses on two prisoners who were incriminated during the anti-colonial rebellions of the mid nineteenth century and were transported to the Straits Settlements. Nihal Singh, a political prisoner from Lahore, was incarcerated in isolation to prevent his martyrdom and denied the supposed benefits of labor reform. Conversely, Tikiri Banda Dunuwille, a lawyer from Ceylon was sent to labor in Melaka as a form of humiliation. Tikiri's many schemes to evade labor damned him in the eyes of the authorities. The personal histories of these two individuals expose how colonial penal policy recognized and manipulated individual differences during a time of rising anti-colonial sentiment. The experiences of these prisoners, the response of their communities and the voices of their descendents offer us a very different entry point into colonial penal history. PMID- 22299198 TI - Writing Indigenous women's lives in the Bay of Bengal: cultures of empire in the Andaman Islands, 1789-1906. AB - This article explores the lives of two Andamanese women, both of whom the British called "Tospy." The first part of the article takes an indigenous and gendered perspective on early British colonization of the Andamans in the 1860s, and through the experiences of a woman called Topsy stresses the sexual violence that underpinned colonial settlement as well as the British reliance on women as cultural interlocutors. Second, the article discusses colonial naming practices, and the employment of Andamanese women and men as nursemaids and household servants during the 1890s-1910s. Using an extraordinary murder case in which a woman known as Topsy-ayah was a central witness, it argues that both reveal something of the enduring associations and legacies of slavery, as well as the cultural influence of the Atlantic in the Bay of Bengal. In sum, these women's lives present a kaleidoscope view of colonization, gender, networks of Empire, labor, and domesticity in the Bay of Bengal. PMID- 22299199 TI - How costly is hospital quality? A revealed-preference approach. AB - We analyze the cost of quality improvement in hospitals, dealing with two challenges. Hospital quality is multidimensional and hard to measure, while unobserved productivity may influence quality supply. We infer the quality of hospitals in Los Angeles from patient choices. We then incorporate 'revealed quality' into a cost function, instrumenting with hospital demand. We find that revealed quality differentiates hospitals, but is not strongly correlated with clinical quality. Revealed quality is quite costly, and tends to increase with hospital productivity. Thus, non-clinical aspects of the hospital experience (perhaps including patient amenities) play important roles in hospital demand, competition, and costs. PMID- 22299200 TI - Medical radiation: too much of a good thing? PMID- 22299201 TI - Social networks and health: communicable but not infectious. PMID- 22299202 TI - On call. I was very interested in your October 2011 article on aspirin and cancer. You commented that aspirin may help prevent cancer, but I can't take aspirin, even in low doses. I use Tylenol for pain and fever--can it also help against cancer? PMID- 22299203 TI - Clinical Schizophrenia & Related Psychoses' (CS) fifth year of publication. PMID- 22299204 TI - Car seat safety. PMID- 22299205 TI - Epigenetics in disease and cancer. AB - Since the discovery of the double-helical structure of DNA, genetic regulation of gene expression has been well elucidated. More recently, another equally, if not more, important scheme of regulation of gene expression, called epigenetics, has emerged to explain the many biological observations that traditional genetic mechanisms have failed to decipher. Epigenetics is a discipline of study on the biological consequences of cellular alterations that do not involve nucleotide changes, as opposed to genetic mutations. Epigenetic changes are reversible and may lead to loss or gain of biological functions. The three most reported mechanisms of epigenetic regulation of gene expression involve changes in: (i) chromatin remodelling, (ii) DNA methylation and (iii) microRNA (miRNA). More importantly, many of the elucidated epigenetic changes are linked to the pathogenesis of human diseases and cancers. In this mini review, core concepts and basic experimental approaches in the study of epigenetic regulation of gene expression are briefly reviewed in relation to disease, with emphasis on cancer. This mini review also intends to highlight the fact that, besides genetics, epigenetics is now a discipline physicians and clinical research scientists can no longer ignore in their pursuit to understand disease and cancer and to develop new therapeutic strategies for treatment. PMID- 22299206 TI - Testosterone testing in adult males. AB - The number of requests for testosterone testing in adult males has been increasing in recent years. In this review, the biochemistry and physiology of testosterone in males relevant to the chemical pathologist or clinical biochemist is outlined. The methodology for total testosterone and various laboratory tests associated with the assessment of testosterone status including free testosterone, calculated free testosterone (CFT), bioavailable testosterone (BAT) and free androgen index (FAI) is then summarised. Clinical and laboratory criteria for the diagnosis of late-onset hypogonadism (LOH) in men are critically discussed with particular emphasis on the interpretation of laboratory test results. Finally, other indications for testosterone testing in adult men such as infertility are also reviewed. PMID- 22299207 TI - Implications of continued upregulation of p16(INK4a) through the evolution from high-grade squamous intraepithelial lesion to invasive squamous carcinoma of the cervix. AB - On integration into the host cervical keratinocyte genome, human papillomavirus (HPV) E7 protein binds pRB,releasing E2F from normally incompetent pRB-E2F complexes and allowing propagation of G1-S transition by the E2F. p16(INK4a), a tumour suppressor protein, increases in reflex response to counter this. 29 histologically re-confirmed low-grade squamous intraepithelial lesions (LSIL), 27 high-grade squamous intraepithelial lesions (HSIL) and 30 invasive cervical squamous carcinoma (SCC) were immunohistochemically stained for p16(INK4a) expression using the CINtec Histology Kit (REF 9511, mtm laboratories AG, Heidelberg, Germany) to re-affirm the notion that integration of HPV occurs predominantly in SCC and possibly HSIL and less in LSIL and normal squamous epithelium (NSqE). Implicit was also the attempt to understand the role of E2F, as indicated by p16(INK4a), in evolution of SCC from HSIL. No ethnic predilection was noted for LSIL, HSIL or SCC. Patients with SCC were significantly older by about 14-years compared with HSIL (p < 0.05) while there was no significant age difference between HSIL and LSIL. p16(INK4a) expression was significantly increased (p < 0.05) in both HSIL (88.9%) and SCC (83.3%) compared with LSIL (3.4%) and NSqE (0%); the NSqE being normal squamous epithelium noted in 17 of the LSIL, 19 HSIL and 5 SCC. From these findings there is suggestion that fundamental upstream events viz HPV integration, E7 upregulation followed by E2F activation occurs at point of transformation to HSIL and continues unrelentingly for another one to two decades before hitherto unclear factors convert a non invasive lesion into an overtly invasive malignant counterpart. Interestingly, the occurrence of HSIL and LSIL in almost the same age group could mean that alteration from episomal to integrated form of HPV may not incur a prolonged incubation period, unlike from HSIL to SCC. PMID- 22299208 TI - P53 expression in invasive pancreatic adenocarcinoma and precursor lesions. AB - Patients with pancreatic adenocarcinoma are known to have a high mortality rate. The 5-year survival rate still remains low even now compared to that of the 1960's despite new advances in management including surgery, chemotherapy, pathological classification and molecular diagnostic technologies. Precursors to invasive pancreatic adenocarcinoma have been identified in the last ten years that include mucinous cystic neoplasm, intraductal papillary mucinous neoplasm and pancreatic intraepithelial neoplasia. p53 protein accumulation in the nuclei is a common molecular event in most human neoplasms. Our objective is to investigate p53 expression in pancreatic adenocarcinoma and precursor lesions and their significance. The selected study material encompassed 31 invasive ductal adenocarcinoma, 15 mucinous cystic neoplasm and papillary mucinous neoplasm, and 27 cases of pancreatic intraepithelial neoplasia including grade 1, 2 and 3. Immunoscore was given for each case based on intensity of staining and percentage of cells positive and compared between precursor lesions and invasive adenocarcinoma. A score of 50 and above was considered significant. The results showed that p53 expression increased progressively and significantly with the grade of pancreatic intraepithelial neoplasia and adenocarcinoma (p-value < 0.001). These findings support the concept of multistep carcinogenesis in pancreatic adenocarcinoma and suggest that p53 inactivation occurs in the progression of precursors to pancreatic adenocarcinoma. PMID- 22299209 TI - Prevalence of uridine glucuronosyl transferase 1A1 (UGT1A1) mutations in Malay neonates with severe jaundice. AB - A number of genetic risk factors have been implicated in the development of neonatal severe hyperbilirubinaemia. This includes mutations in the uridine glucoronosyl transferase 1A1 (UGT1A1) gene which is responsible for unconjugated hyperbilirubinemia in Gilbert's Syndrome. We studied the prevalence of UGT1A1 gene mutations in a group of Malay neonates to determine whether they are risk factors to severe neonatal jaundice. One hundred and twenty-five Malay neonates with severe hyperbilirubinemia were studied. Ninety-eight infants without severe hyperbilirubinaemia were randomly selected from healthy Malay term infants (controls). DNA from EDTA cord blood samples were examined for UGT1A1 mutations nt211G > A and nt247T > C using established Taqman SNP genotyping assays and the UGT1A1*28 variant was detected by the Agilent 2100 bioanalyzer. All samples were also screened for common Malay G6PD variants using established techniques. The frequency of UGT1A1 211G > A mutation is significantly higher in the severely hyperbilirubinemic group (13%) than the control group (4%; p = 0.015) and all the positive cases were heterozygous for the mutation. There was no significant difference in the frequency of UGT1A1*28 mutation between the severely hyperbilirubinemic (3.5%) and the control group (0.01%; p = 0.09). None of the neonates in both groups carried the nt247 T > C mutation. The prevalence of G6PD mutation was significantly higher in the severely jaundiced group than control (9% vs 4%; p = 0.04). In conclusion, nt 211 G > A alleles constitute at least 12% of UGT1A1 mutations underlying unconjugated hyperbilirubinemia and appears to be a significant independent risk factor associated with severe neonatal hyperbilirubinemia in the Malay newborns. PMID- 22299210 TI - Analytical and diagnostic performance of an automated anti-CCP assay. AB - AIM: Autoantibodies against cyclic citrullinated peptide (anti-CCP) are considered to be a sensitive and specific marker for rheumatoid arthritis (RA). This study evaluated the diagnostic and analytical performances of the automated anti-CCP assay. MATERIALS AND METHOD: Sera from 80 patients with established RA, 65 from other rheumatic diseases (non-RA) and 55 from healthy controls were studied using second generation anti-CCP. Rheumatoid factor (RF) was also assayed in each sample, and the results were compared to the anti-CCP findings. Serum pools were used to determine the precision and linearity. RESULTS: At a cut-off of 7.4 U/ml for anti-CCP, the sensitivity and specificity for RA were 65% and 98% respectively. RF had a sensitivity of 58% and a lower specificity of 93% than anti-CCP. CONCLUSION: The high specificity of the assay suggests that anti-CCP is useful in the diagnosis of rheumatoid arthritis and in our cohort of study population anti-CCP exhibits a better diagnostic value than RF. A considerable proportion (28%) of RF-negative RA patients were anti-CCP positive. Based on analytical performance of the assay, we conclude that full automation and high throughput features of AxSYM makes it an ideal platform for routine testing of anti-CCP. PMID- 22299211 TI - Real-time quantification for BCR-ABL transcripts in chronic myeloid leukaemia patients in UKMMC, Malaysia. AB - Molecular pathogenesis of chronic myeloid leukemia (CML) is well established and molecular monitoring for patients with CML has become an important practice in the management of patients on imatinib therapy. In the present study, we report the use of RQ-PCR method for detection of BCR-ABL fusion gene for our CML cases. We performed a two-step RQ-PCR on bone marrow aspirates or peripheral blood of 37 CML patients. Quantitative expression of BCR-ABL fusion gene was carried out relative to the expression of a housekeeping gene as endogenous control to compensate for uneven cell numbers, RNA quality, or variations in reverse transcription efficiencies. Twenty-four of these patients were pre-treated with hydroxyurea or alpha interferon prior to the imatinib therapy. Their BCR-ABL fusion gene levels were monitored for 18 months. All samples processed were evaluable. The PCR amplification efficiency of the ABL gene is 90.5% (0.2158) and the BCR-ABL gene, 93.4% (0.1573). PMID- 22299212 TI - Field evaluation on the effectiveness of a modified approach of chemical fogging against the conventional fogging in controlling dengue outbreak. AB - A field evaluation on the effectiveness of a modified approach of chemical fogging of insecticides against the conventional method was carried out in the Seremban district within the state of Negeri Sembilan, Malaysia from 7th February 2003 to 7th September 2003. In the 3 months period, November 2002 to January 2003, prior to institution of modified approach of chemical fogging, 27 of 42 (64.3%) dengue outbreaks were successfully controlled within the stipulated time frame of 14 days by the conventional approach of thermal chemical fogging. However, during the period when the modified approach of chemical fogging was instituted, 25 of 27 (92.6%) dengue outbreaks within the same district were successfully controlled within the 14-days time-line. Statistically, the modified approach of chemical fogging significantly improved the success rate of achieving dengue outbreak control within the stipulated time frame (chi2 = 5.65, p = 0.01745). The modified approach of chemical fogging also appeared to reduce the number of dengue cases recorded in the same district. This small pilot study shows that the modified approach of chemical fogging reduced cost in carrying out each fogging activity to control dengue outbreak. It also substantially reduced the required time taken to complete each fogging activity in comparison to the conventional approach. Thus, it enabled similar number of workers to cover more localities simultaneously affected by the outbreaks. In addition, the modified approach reduced the exposure time to hazardous insecticides for each worker doing hand-held thermal fogging. PMID- 22299213 TI - Retroperitoneal liposarcoma in an adult patient with Down syndrome. AB - Retroperitoneal liposarcoma is a rare solid tumour of mesenchymal origin with an incidence of 2.5 per million population. We report what is, to the best of our knowledge, the first case in the English literature of retroperitoneal liposarcoma in an adult patient with Down syndrome. The tumour was surgically resected with no use of adjuvant chemotherapy or radiation. No recurrence was found at follow-up 2 months postoperatively. Clinicians should consider retroperitoneal liposarcoma in the differential diagnosis of abdominal distention in adult patients with Down syndrome. PMID- 22299214 TI - Malignant myoepithelioma of the breast: case report with review of literature. AB - Myoepithelial lesions of the breast are extremely rare and can present with a diverse morphology. We report a case of malignant myoepithelioma characterized by proliferation of atypical oval to polygonal cells expressing typical myoepithelial markers. A 45-year-old lady presented with a mass in the left breast. Fine needle aspiration yielded a cellular smear with large papillae-like clusters of monomorphic cells with naked nuclei in the background. A diagnosis of sub-areolar sclerosing duct hyperplasia was made on cytology and the patient underwent excision. The surgical specimen showed a grey-white 5x3 cm mass on cut surface. Histopathology revealed mitotically active (5-6 per 10hpf) oval to polygonal cells tumor cells with clear to eosinophilic cytoplasm arranged in the form of nodules separated by dense sclerotic stroma mimicking clear cell or adenoid-cystic carcinoma. A diagnosis of malignant myoepithelioma was made as the cells were CK14 and SMA positive, and negative for ER and PR on immunohistochemistry. We discuss the unusual morphological features of malignant myoepithelioma, cytological findings and the important differential diagnoses of malignant myoepthelial lesions. A high degree of suspicion with a keen eye for morphological details coupled with relevant immunohistochemistry will aid in arriving at the diagnosis. PMID- 22299215 TI - Sclerosing lobular hyperplasia--cytological similarity to fibroadenoma. AB - Mammary sclerosing lobular hyperplasia (SLH) is a rare, benign, fibroproliferative tumour-like lesion of adolescent and young women often of African-American heritage. Fine-needle aspiration cytology of mammary SLH shows characteristic features that include an absence of stromal fragments. We report a 45-year-old woman who presented with a gradually enlarging, painless, mobile 4-cm tumour in her left breast. Fine-needle aspiration cytology performed preoperatively was characterized by some fibroadenoma-like features including the presence of stromal fragments and bare nuclei. However branched tubular fragments, typical of fibroadenoma, were not seen. A diagnosis of benign epithelial lesion of the breast was offered, and the possibility of a fibroadenoma was suggested. Excision biopsy histology revealed SLH. The key cytological features of mammary SLH are bland ductal epithelial cell clusters, few scattered fragments of stroma, relatively clean background with a fair number of bare nuclei. However these are not diagnostic as they overlap with those of fibroadenoma and distinction between the two benign entities is of no clinical significance. The definitive diagnosis of SLH requires histopathological evaluation. PMID- 22299216 TI - The 1% birth. Why baby Beyonces are little profit centers for hospitals. PMID- 22299217 TI - Streamlined billing: health plans complying with standards, AHIP says. PMID- 22299219 TI - Ky. deal forms with just two. PMID- 22299218 TI - Ascension revamps to grow: subsidiaries split from system under reorganization. PMID- 22299220 TI - One for the record books: hospital profit margins hit highest level in decades. PMID- 22299221 TI - Fraud prosecutions up 69%: shift in investigators' tactics, evolution in technology seen as reasons. PMID- 22299222 TI - Referendum on reform: America has begun voting, with the future of healthcare policy a top-tier issue. PMID- 22299223 TI - Heading off compliance headaches: three experts discuss strategies to avoid legal pitfalls of federal programs. PMID- 22299224 TI - IT demand goes global: many markets outside U.S. posting strong growth. PMID- 22299225 TI - Assertive or antiquated: ProMedica vows to appeal loss against FTC as questions loom over whether mergers lead to efficiencies or clout. AB - ProMedica vows to fight the feds over the acquisition of St. Luke's Hospital. Here is what they have to say. "The cost of healthcare is a real problem for all Americans, and the commission seeks to address this national problem by using all the tools Congress gave to us, and by devoting significant resources so that competition will enable market participants to deliver on the promises of cost containment and continued excellence and innovation," says the FTC's Jon Leibowitz. PMID- 22299226 TI - SGR bandage: GOP legislation offers temporary doc fix. PMID- 22299227 TI - Unacceptable losses: critics hit lack of fraud credit in MLR regs. PMID- 22299228 TI - Not everything's fixed: nurse ranks rise, but some say it may be temporary. PMID- 22299229 TI - Debt dealings: chains refinance amidst lower interest rates. PMID- 22299230 TI - Role reversal: deal would give not-for-profit ownership stake. PMID- 22299231 TI - Falling prices: CMS drops cost of claims data in final rule. PMID- 22299232 TI - Three strikes... Executives aren't the only ones who should be ejectable. PMID- 22299233 TI - Linking technologies: IT experts on issues they faced in getting their systems' components to mesh. PMID- 22299234 TI - Looming threat: Jan. 1 brings 1% cut if eRx requirements not met. PMID- 22299235 TI - [Pharmacovigilance in pharmacy practice]. AB - Although rigorous clinical studies are conducted on drugs before they become available to the patient, some side effects are often only detected after marketing. It is the role of pharmacovigilance to identify these effects. Notification of adverse reactions by health professionals and pharmaceutical companies contribute to a better understanding of the safety profile of a drug and thus to better care for patients. As a care provider and in the context of pharmaceutical care, the pharmacist has a responsibility and an active role in monitoring the safe use of medicines. This article deals with the organization of pharmacovigilance in Belgium and some practical aspects PMID- 22299236 TI - [Thalidomide Celgene: a practical guideline for community pharmacists]. PMID- 22299237 TI - [Consumer study on the use of patient information leaflets]. AB - The aim of this study was to get a clear idea of the reading frequency of the patient information leaflet (PIL) and to set up a profile of the reader in specific. Apart from that, we also wanted to evaluate the impact of the internet in the patient's search for information on health and medication. Do patients consult the digital PIL and is the FAGG website known by common people? In order to answer these research questions, a specific inquiry was performed in 800 respondents. Some interesting conclusions can be drawn: only one out of four participants reads the full PIL when purchasing a medicine they never used before. People who always read the PIL are mainly older than 65. However, the largest amount of people who never reads the PIL is also situated in the plus 65 scale. In general, men show little interest in reading the PIL unlike woman, who read clearly more often the PIL. The parts of the PIL most often read by patients are the sections on dosage (section 3) and side effects (section 4). Unfortunately, too little attention is paid to the section 2, which contains the most warnings, such as contra-indications. The most important reason why the PIL is not read is because patients believe they get sufficient information from the doctor and the pharmacist. Another remark is that the internet is used by more than half of the respondents to search for health-related information. There is also a remarkable difference between men and woman, men rarely search for health information or information on medicines on the internet. The number of respondents searching for leaflets on the internet is quite limited. Additionally, the Federal Agency Medicines and Health Products (FAMHP) website is unknown to most internet users. We can conclude that the actual PIL is read too little. In order to make the PIL more appealing and even more patient friendly than it is actually, taking patients' needs into account should be a priority. The digital leaflet should be drawn attention to in order for patients to make more use of the information that is available to them. PMID- 22299238 TI - [Influenza vaccines dispensed in community pharmacies during the 2010-2011 flu season]. AB - In this article we consider the delivery of influenza vaccines in the Belgian communiy pharmacies during the influenza season 2010-2011. We compare this season with the previous influenza seasons and consider the age distribution the flu vaccinated patients. The vaccination rate of the entire population is compared to the vaccination rate among the risk group of diabetic patients. Also the market introduction of intradermal vaccinations in investigated. PMID- 22299239 TI - [Genetic principles of food related problems -- phenylketonuria]. PMID- 22299240 TI - [Indacaterol (Onbrez Breezhaler), oral inhalation]. PMID- 22299241 TI - [Back pain only at night and when lying down. The intervertebral disks were not the problem. Echinococcosis]. PMID- 22299242 TI - [Christmas money. How to prevent the bonus from becoming an obligation?]. PMID- 22299243 TI - [Secondary prevention of myocardial infarct. A new anticoagulant improves survival prospects]. PMID- 22299244 TI - [Secondary prevention. Pills without co-pay reduce complications after myocardial infarct]. PMID- 22299248 TI - [Atrial fibrillation. PALLAS study: when dronedarone becomes a risk]. PMID- 22299249 TI - [ADOPT study. Longer thrombosis prevention in internal medicine patients has no advantage]. PMID- 22299250 TI - [Dysphagia is an alarm symptom. First step: excluding a malignancy]. PMID- 22299251 TI - [Achalasia. New endoscopic therapy saves operation]. PMID- 22299254 TI - [Naturopathy consultation. Polyneuropathies]. PMID- 22299255 TI - [Improve living with cancer]. PMID- 22299256 TI - [Children of cancer patients: "will you be ok again, Mum?"]. PMID- 22299257 TI - [Cancer personality: the resistable descent of a myth]. PMID- 22299258 TI - [Tinnitus]. PMID- 22299259 TI - [Safe driving in old age?]. PMID- 22299260 TI - [Sleep apnea causes damage to the brain]. PMID- 22299261 TI - [New goals in COPD treatment. From symptom control to prevention of exacerbations]. PMID- 22299263 TI - A look on nursing actions. PMID- 22299262 TI - [CED therapy with infliximab. Rapid and lasting remission - complete mucosal healing]. PMID- 22299264 TI - [The approach to the interface between health and environment in the training of nurses]. AB - This study aimed to know how nursing professors perceive the interface between health and environment. This is a descriptive study with a qualitative approach developed with six nursing professors from different areas in the process of training nurses. The data were collected through semi-structured interviews in 2010 and underwent a process of content analysis. The data analysis allowed the emergence of categories, namely: Health and environmental interface: a relation of cause and consequence, Discussion on the issue of health and environment in vocational training: a gap in the educational process, and Health and environment a cross-sectional content. Based on the understanding that there is interaction between health and environment, the professors emphasize that the environment should be a cross-sectional theme in the curriculum proposal for the Nursing undergraduate major, since they show gaps in addressing the issue. PMID- 22299265 TI - [The environment of the Intensive Care Center and the work of the nursing staff]. AB - This is a descriptive exploratory study with a quantitative approach. It aims to characterize the environment of the Intensive Care Center (ICC) in regard to its physical area, material resources and equipments, and to identify factors concerned to the work of nurses. It investigates environmental factors that contribute to an aesthetically harmonious, functional and humanized space and that favor the performance of nursing work. The units that make up the ICC meet the recommendations of the National Health Surveillance Agency (ANVISA) in the evaluated items. he following favorable work conditions were highlighted: thermal conditions, color of the ceiling, walls and floors, luminosity. The following unfavorable work conditions were highlighted: outdoor spaces, privacy and individuality of clients and noise. The conclusion is that the facilities of the units meet the minimum recommendations of ANVISA. Both favorable and unfavorable environmental work conditions were identified. The creation of better environmental conditions allows a better staff performance, influencing positively quality, safety, and job satisfaction. PMID- 22299266 TI - [User's representations of chronic diseases and educational practice]. AB - This is a qualitative research study held between October, 2008, and March, 2009, with 45 users over 60 years of age from a Health Unit, which aimed to identify their representations of chronic disease. Inerviews were carried out to collect chronic disease's representation. Three team meetings were also carried out, with an average of 8 users. Twenty-four (24) users participated in this step. The themes brought out of their discourses were: "The arrival of the disease: explanatory factors"; "The mystery of the bodyly changes: an obligation to change", and "The importance of learning and sharing the experience". Participants recognized the factors related to the disease onset and their commitments, the changes necessary to keep living and put off complications, and they also valued the exchange of experiences through dialogue in educational activities. PMID- 22299267 TI - [Care of children and mothers: research on preventable deaths in children under five years]. AB - This study aims to evaluate the treatment of children and mothers in basic health units based on the investigation of deaths in children under five years. This is an evaluative study, that analyzed 41 deaths ocurred in 2008 in the city of Maringa, state of Parana, Brasil. 90.2% of these deaths were preventable. 38.5% of the pregnant women had theirfirst prenatal consultation in the first quarter of pregnancy. 50.0% had more than six consultations. 73.1% were assessed for risk pregnancy. 34.6% of chart records had information on prenatal laboratory tests. 50.0% of births occurred by cesarean section. 87.5% of charts contained records of child growth monitoring and risk assessment of newborns. None had records of neuromotor development. 50.0% had complete vaccination records. 75.0% received home visits from a family healthcare team. All children at low risk had three visits to doctors. Only one high-risk newborn reached seven medical consultations. The conclusion is that there are failures in the professional records of prenatal care, as well as in the quality of monitoring of children considered at risk. PMID- 22299268 TI - [Characterization of bed falls sustained by inpatients in a university hospital]. AB - This is a descriptive study which aimed to characterize the profile, risk factors, and Nursing Diagnoses (NDs) of adult patients who have fallen from bed during hospitalization. We analyzed 53 reports of bed falls, during the period from December 2009 to May 2010, in a big hospital. Results showed higher occurrence in male patients. Greater prevalence occurred in patients age 60 and above, during the night shift and the clinical unit. Only 13% presented the "Risk for falls" ND, although they had on average of 11 risk factors for it. Findings resemble what is described in world literature, reinforcing the need to install preventive measures for falls and to mitigate risks. PMID- 22299269 TI - [Undergraduate students' knowledge about the prevention of breast cancer]. AB - This study aimed to identify what undergraduate students know of factors for breast cancer prevention. This was a quantitative, exploratory and descriptive study, developed in a University in the state of Santa Catarina, Brazil with 50 students enrolled in nursing, physiotherapy and psychology programs in the first semester of 2008. The data were collected from February to April 2008. A semi structured questionnaire and descriptive statistics were used. Results showed that students of nursing and physiotherapy demonstrated greater knowledge about the issue than the psychology students. Mentioned prevention factors: consumption of vegetables, greens and fruits, physical exercises and breastfeeding. Conclusions indicate that the level of students' knowledge about factors that can prevent breast cancer, in an interdisciplinary perspective, is important to rethink the inclusion of health education as an essential curriculum content to promote a healthy university. PMID- 22299270 TI - [Teaching strategies of nursing care: a look on pedagogical trends]. AB - To determine the teaching strategies adequate for the contents and concepts imbricated in care is a challenge for nursing educators. This qualitative, descriptive and exploratory study aimed to know the strategies applied to teach nursing care used by ten nurses, professors of the Nursing Department in a University in the metropolitan area of the city of Porto Alegre, state of Rio Grande do Sul, Brazil. The information was collected through the Focal Group technique, from June 2004 to March 2005. The thematic analysis of the data resulted in the category Strategies to Teach Care, with the sub-categories demonstration, exhibition, observation, and discussion. The evidences point to attempts of replacing the traditional content transmission notion, without however, effectively showing another pedagogical tendency. We can conclude that the technical competence is still privileged which leads to a disregard of the learning that aims at the development of a reflexive and critic stance. PMID- 22299271 TI - [Care management: nurses' actions in a hospital emergency service]. AB - This study aimed to analyze care management actions performed by nurses in a hospital emergency service. This is a qualiative research of the case study type, carried out with nurses from the Emergency Service of a University Hospital in southern Brazil. The data were collected through participant observation and semi structured interviews, and analyzed using thematic analysis. The results show nurses' actions in care planning, forecasting and provisioning of resources, supervision, leadership and training of the nursing team. In care planning, there is the execution of the nursing process and the control of the realization of laboratory and radiological tests. The actions of forecasting and provisioning of resources were: elaboration of the monthly schedule of employees, daily distribution of the staff and the management of material resources. Leadership encourages the planning of care, the coordination of the nursing staff and the delegation of activities. PMID- 22299272 TI - [Introduction of the Braden Scale in an intensive care unit of a university hospital]. AB - This is a prospective and longitudinal study which aimed to introduce the Braden Scale (BS) as an instrument to predict the risk of pressure ulcer (PU), and to analyze the results of its use in an intensive care unit. The sample was of 74 patients and the data were obtained by an instrument containing BS. Such data were analyzed by a simple descriptive statistic. 58 patients (78.37%) had a score < or = 13 and PU incidence of 25.67%. In 45 patients (60.80%), BS was daily filled in. From these patients, 5 (11.10%) developed PU. In 29 patients (39.10%), BS was not daily filled in. From these patients, 14 (48.20%) showed PU Results showed the efficiency of BS, which allowed identifying patients with PU risk. The difficulties of using BS refer to the periodic filling, which shows the need to educate and prepare nurses to use BS in the care of patients. PMID- 22299273 TI - [Bachelor and teaching degree in nursing: experiences and expectations of nursing students]. AB - This is a phenomenological study that aimed to understand the experience of the student enrolled in both the Bachelor and the teaching undergraduate degree in nursing at the same time. Interviews with eight nursing students from a public university of Minas Gerais, Brazil, were undertaken. Analyses were conducted based on the social phenomenology of Alfred Schutz. Results showed that according to the pupils, there is no connection between the teaching courses and the Bachelor ones, but they also highlighted that the teaching degree helps educational activities in nursing. The students have interest in working with health education and to become nursing teachers. They also consider that the dual degree allows the expansion of knowledge and generates better expectations related to professional practice. However, it has gaps which need to be reviewed by those who work in nursing education, addressing the specific theoretical and practical needs of nursing students. PMID- 22299274 TI - [The symbolic elements in the Anna Nery monument in Rio de Janeiro, Brazil]. AB - The objective of this study was to examine the symbolic elements of the statue and memorial plaques in honor of Anna Nery offered by the Brazilian Red Cross, as a symbolic effect on society. The documentary analysis was performed mainly through institutional press records and images, which were interpreted by means of the notions of object representation and object bodyly hexis. Results showed that the object representations in the statue of Anna Nery lacked a representation of her articulated to her bodyly hexis, which led to the interpretation of the monument--both the statue and the four narrative plaques- as a tribute to the Brazilian woman. PMID- 22299275 TI - [Production of hospitalization in the Unified Health System in the region of Ribeirao Preto, Brazil]. AB - This study aimed to characterize the dynamics of the physical and financial production of hospitalizations in 25 cities in the region of Ribeirao Preto, state of Sao Paulo, Brazil, area of the Regional Department of Health XIII (DRS XIII). This was a descriptive and exploratory research, with documentary research as the method of data collection. The study population was constituted by hospitalizations, processed by the Hospital Information System of the Unified Health System (SIH-SUS), according to specialty, year and municipality,from 1996 to 2007, in 23 hospitals hired or contracted by SUS in the region. The data were coded in spreadsheets. Ribeirao Preto hospitalizations represented 64% of production, and hospitalization in the nearby region, 36%. The financial output was 14.6% in the region and 85.4% in Ribeirao Preto. There are possibilities of hospitalizations with increased cost and complexity in Ribeirao Preto. The production varies across specialties. The results provide order flow of users, monitoring of production between hospitals, assisting the management of the particularities of the local health system in hospital care. PMID- 22299276 TI - [Brazilian technological output in the area of nursing: advances and challenges]. AB - This article aims to analyze the patents registered in the nursing area, since these patents may be used as an indicator of the technological development in the area. It presents and discusses national technological productions, tracked through the "nursing" keyword, patented in the period from 1990-2009. This is a retrospective documental research, using, as a source, data from the National Industrial Property Institute (INPI). The information gathered is discussed in relation to the appropriation of the technologies, the incentive to develop them and register them as a source of knowledge in the nursing field, aiming the practice of care. Light and light hard technology productions are increasing in the nursing field. However, these are not registered and patented. The technological advance in the nursing field is emergent and needs policies for its development. PMID- 22299277 TI - [Health promotion in the religious scenario: opportunities for nursing care]. AB - This was a qualitative study of the documentary type carried out in the first half of 2008, and it aimed to describe the practices of health promotion developed in the religious scenario in a city in the countryside of Ceara, Brazil. Information were collected through audio-taped interviews with the priest in charge of the parish and the three coordinators of projects linked to the Catholic Church, selected by the identification of projects with the priest. The results show that promotion and health education are present in the activities developed by volunteers in the religious scenario. The church seeks to change attitudes and to promote the adoption of healthy behavior by individuals, through individual and collective actions. There is an urgent need to insert healthcare professionals in this scenario, strengthening it as a social support, gradually reducing the assistential activities and intensifying those aimed at health promotion with the support of nursing, in order to improve healthcare in this scenario. PMID- 22299278 TI - [Quality of life of elders with Alzheimer's disease and of their caregivers]. AB - The objective of the study was to identify the quality of life (QoL) of elders with Alzheimer's Disease (AD) and of their caregivers. This is a descriptive exploratory study carried out with 50 elders and caregivers in the city of Maringa, state of Parana, Brazil. The data were collected from November, 2010, to January, 2011, with the use of the Quality of Life in Alzheimer's Disease Scale. The average of the total scores for patients and caregivers were 26.36 and 35.04 points, respectively. The fields home (98%) and family (72%) presented greater satisfaction for both caregivers and elders. The fields memory and tasks (92%) for the caregivers, and leisure (52%) for the elders reached larger dissatisfaction indexes. It is considered that the caregiver's QoL reflects directly upon the care and, therefore, it should also be considered in the planning and implementation of care to the elderly with AD. PMID- 22299279 TI - [Quality of life of breast cancer patients in adjuvant therapy]. AB - This study aimed to assess the Quality of Life (QoL) and to identify the domains affected in breast cancer patients receiving adjuvant therapy and to correlate them with sociodemographic, clinical and therapeutic characteristics. This is a cross-sectional study with 35 patients, developed from August, 2007, to December, 2008. The Quality of Life Core-30-Questionnaire (QLQ-C30) instrument was used. The general Quality of Life was considered less than satisfactory. The most affected domains were: emotional function, insomnia, pain and fatigue. In the correlations, the patients above 60 years presented worse scores on emotional function, the patients submitted to the surgery related more constipation, patients receiving radiotherapy presented worse scores on general QoL and the ones that had more than six cycles of chemotherapy presented the emotional function affected and dyspnea. The conclusion is that the adjuvant treatments had affected in some way the patients, causing a deficit in the emotional function and other related symptoms, and impaired their QoL. PMID- 22299280 TI - [Quality of life of patients with colorectal cancer receiving outpatient chemotherapy]. AB - This is a cross-sectional study with a descriptive quantitative approach, which aimed to assess the quality of life (QOL) of patients with colorectal cancer receiving outpatient chemotherapy. The research was conducted in an Outpatient Chemotherapy Unit at a hospital in southern Brazil, whose patients were diagnosed with colorectal cancer and were treated with the 5-FU protocol. The sample had 48 participants who were undergoing chemotherapy for a period of six months. A questionnaire, the WHOQOL-Bref was used as an instrument. In the results, the age of 50 years or more with at least a month and a maximum of 11 months of treatment prevailed. The domains of the WHOQOL-Bref more significantly affected were the psychological and the social relations one, respectively, with significant differences in responses regarding overall QOL in those who were in the first cycle of treatment from those already in the 6th cycle. PMID- 22299281 TI - [Sexuality of the elderly: behavior for the prevention of STD/AIDS]. AB - This study deals with the theme "elders facing sexually transmitted diseases (STDs)" and it aims to identify the behavior of the elderly in the prevention of STD/AIDS. It is a qualitative, exploratory and descriptive study using a semi structured questionnaire with open questions. The study subjects were six seniors who participated in a group in a Basic Health Unit. The results showed that older people have information about STDs, but it also evidences a poor observance of condom use. We conclude from this study that the aging process requires awareness of health professionals that the elderly are sexually active and therefore exposed to STDs, and that the issue of condom use should be a natural matter during consultations, group meetings and events that reach this population. PMID- 22299282 TI - [Sexual violence against adolescents: notifications filed in the Child and Adolescent Protective Services in the city of Campo Grande, state of Mato Grosso do Sul, Brazil]. AB - This study examines reports of sexual violence against adolescents in 2007 and 2008 made with the North- and South-District Child and Adolescent Protective Services of Campo Grande, the capital city of the state of Mato Grosso do Sul Brazil. Data for this retrospective, descriptive and quantitative research were collected from the services' archives on sexual violence against adolescents. RESULTS: most victims were females. Reports predominantly concerned boys and girls from 10 to 14 years of age. Most offenders were males. The majority of reported cases occurred at home. When addressing cases of sexual violence, healthcare professionals should adopt a stance permeated by respect for the victims and their families. This requires providing a receptive environment, so as to ensure the level of privacy required for victimized adolescents to report facts and express their feelings. PMID- 22299283 TI - [Use of sweet solutions for neonatal pain relief in premature newborns: an integrative review]. AB - The repeated painful experiences in newborns may have short- and long-time effects, especially in premature infants. The use of sweetened solutions during painful procedures has been recommended as a measure of pain relief. This study aims to evaluate the evidence of the effect of oral sucrose or glucose for acute pain relief in premature infants. An integrative review was conducted in the MEDLINE and LILACS databases. Eight articles were selected from 2005 to 2010. The analyzis of these articles revealed the analgesic effect of glucose and sucrose in acute procedures. No significant side effects were found in infants who received glucose/sucrose. We emphasize the importance of the use of the pain assessment scale most closely related to the predominant population in the Neonatal Intensive Care Unit, a scale easy to be used and handled by health professionals. PMID- 22299284 TI - [Quality management by nurses in Hospitals' Emergency Services: integrative literature review]. AB - This study aimed to analyze publications related to the activities of nurses managing the quality in the Emergency Services of Hospitals. An integrative literature review identified 4780 articles of which 8 were selected considering the criteria: full articles, published from 2000 to 2010; available in Portuguese; indexed in the databases of the Virtual Health Library. All the material was analyzed through Content Analysis. Two themes emerged Working in the structuring of the nursing staff to the quality of care and Nursing actions managing the quality of care. The conclusion is that the promotion of the quality of care provided in Hospitals' Emergency Services is linked to the actions promoting the humanization of both care and caregivers, and that the role of the nurse in the User Reception with Risk Rating is a key strategy for managing quality in services. PMID- 22299285 TI - [Woman's participation in the decision process of the pregnancy and puerperal cycle: nursing care integrative review]. AB - This is an integrative review that aims to identify the contribution of nursing care for woman's participation in the decision process of the pregnancy and puerperal cycle, as described in Brazilian scientific publications. The scientific productions were retrieved in May, 2010, from the Virtual Library of Health (Biblioteca Virtual em Saude) database. From the eight articles reviewed, two themes stood out: Contributions of nursing care to the woman's participation in the decision process of the pregnancy and puerperal cycle; and Limitations of nursing care to the woman's participation in the decision process of the pregnancy and puerperal cycle. The following review supports the production of knowledge in nursing, by identifying a gap in what nurses know and do about this issue, as shown by the lack of nursing researches that concern, specifically, the participation of the woman in the decision process during the pregnancy and puerperal cycle and the possible contributions of nursing care to ensure women of this right. PMID- 22299286 TI - [Tendency of the studies on moral harassment and nurses]. AB - This is an Integrative Literature Review that aims to analyze productions on moral harassment in nursing published in journals in Brazil and abroad. Articles from 1999 to 2009 were researched in online databases, comprising a sample of 18 publications. After careful reading seven thematic categories were built: evaluation of the moral harassment; behaviors of moral harassment on the part of male nurses; consequences of the moral harassment; coping strategies adopted by nurses; moral harassment in nursing as race and gender discrimination; moral harassment among nursing professionals; institutions as propagators of moral harassment. Results confirm the presence of moral harassment in nursing. However, they indicate that these professionals have been accepting and reproducing this kind of violence as part of the organizational culture, thus showing a need to educate this population and the health institutions themselves about moral harassment and its damages. PMID- 22299287 TI - [International scientific output on the International Classification for Nursing Practice]. AB - The International Classification for Nursing Practice (ICNP) is a classification system that aims at an universal standardized language for nursing. This article aims to discuss the results of studies addressing ICNP. This is a review of the literature in the database of the Virtual Health Library, by the term "ICNP" with coverage until 2009. 124 articles were found; 65 were analyzed and their contents were grouped in nine categories: general approaches; applicability in practice; assessment ratings; experiments with computational resources; development and inclusion of terms; approach to classification systems; use to anchor the building of nursing statements; translations; and others. It was found that few studies present projects or evaluate the practical applications of ICNP. The majority discusses conceptual issues or compare ICNP with other classification systems. Several studies conclude about the appropriateness and relevance of ICNP, despite pointing a need for improvement. PMID- 22299288 TI - [Semiotic Studies Lab for Patient Care Interactions]. AB - The aim of this experience report is to present the Semiotic Studies Lab for Patient Care Interactions (Laboratorio de Estudos Semioticos nas Interacoes de Cuidado - LESIC). The lab was set up at the Nursing School of the Federal University of Rio Grande do Sul (UFRGS), Brazil in 2010. It has the purpose of providing didactic and pedagogical updates, based on the Theory developed by the Paris School of Semiotics, that enable the increase of knowledge and interactive/observational skills regarding the nature and mastery of human care. PMID- 22299289 TI - Evaluation of circulating immune complexes and antiphospholipid antibodies (anti beta 2 glycoprotein 1) in heroin addicts and their clinical significance. AB - INTRODUCTION: Earlier studies have reported that heroin might cause the structural and antigen changes on numerous tissues, organs and subsequent development of autoimmune reactions (production of antibodies and creation of immune complexes) as a result the immunotoxic effect of heroin. The aims of our study were to: a) Evaluate CIC and antibeta2GP1 in heroin addicts; b) Correlate between the values of the obtained CIC and antibeta2GP1 (stratified by the duration and route of heroin application); c) Compare the CIC and antibeta2GP1 in heroin addicts and the control group and d) Assess the clinical importance of CIC and antibeta2GP1 in heroin addicts. PATIENTS AND METHODS: This was a cross sectional study performed at the University Clinic of Toxicology and the Institute of Transfusiology, Skopje, Republic of Macedonia. Patients referred to the Clinic for clinical examinations who met the inclusion criteria were analyzed. Protocol for work was the following: 1.) detailed anamnestic data, 2.) a whole set of laboratory biochemical blood and urine analyses, 3.) examination with the Schiller's twelve-channel ECG; 4.) toxicological analyses for opioids in a urine sample; circulating immune complexes and 5.) antiphospholipid antibodies (antibeta2GP1, fractions: IgA, IgG, IgM). The obtained results were statistically analyzed. RESULTS: We included 37 heroin addicts and a control group of 27 healthy subjects. Male abusers predominated over female in--28 (76%) subjects; mean age being 26 +/- 5.06. The results which refer to the increased values of circulating immune complexes have shown a high statistically significant dominance of heroin addicts, in comparison with the control group (p < 0.01) and increased values above the reference ones of IgG antibeta2GP1, alone in the group of intravenous heroin abusers (p < 0.025). The mean duration of the heroin use in intravenous abusers was 6.21 +/- 3.25 years, whereas in those snorting heroin was 5.15 +/- 2.26 years. Duration of heroin application was in a positive correlation with IgG antibeta2GP1 (p = 0.35). CONCLUSIONS: Our data showed that heroin dependent patients in our study had increased values of circulating immune complexes and changes in IgG and IgM antibeta2GP1 with significantly increased values of IgG antibeta2GP1 in the intravenous heroin abusers. The duration of heroin application is in direct proportional relationship with IgG antibeta2GP1. Heroin addicts had significantly higher values of circulating immune complexes and statistically significant difference in IgG antibeta2GP1, in comparison with the control group. Changes in the fractions of antibeta2GP1 and CIC suggest a possible relation with the somatic changes found in heroin addicts (i.e. thrombocytopenia, reduced renal clearance, etc). PMID- 22299290 TI - Role of chronic hemodialysis in thyroid gland morphology disorders. AB - Thyroid gland morphology is affected in patients with chronic kidney disease. THE AIM: The purpose of this study was to compare thyroid gland morphology among patients on chronic hemodialysis (HD) and healthy participants and to assess the duration of dialysis on thyroid disorders. MATERIAL AND METHODS: Prospective study included 80 participants divided into two groups. Study group included 40 patients on (HD) who were divided in two subgroups, according to the time spent on dialysis (i.e. under and over 72 months). The exclusion critheria was represented by the previous thyroid disorders and systemic illnesses. The control group included 40 healthy participants. The blood samples were taken for standard laboratory analysis, total and free thyroid hormone levels. RESULTS: Thyroid ultrasound was performed, thyroid wolume was calculated and the echostructure assessed. Mean values of thyroid volume were increased in HD patients (e.g.18,88 +/- 3,20 ml, p < 0.01). Diffuse goiter was found in 35% (n = 14) patients on HD (p = 0.01). In a subgroup of patients (i.e. with time on HD < 72 months), the significant and more frequent was multinodular goiter, in 15.38% (n = 4) (p = 0.03). There was no significant correlation between the time on dialysis , thyroid volume (r = -0.05, NS) and TSH levels (r = 0.14, NS). A significant, positive correlation between the thyroid volume and TSH levels was observed in HD group of patients (r = 0.24 p < 0.05). CONCLUSION: Thyroid disorders are more common in patients on HD compared to general population. These findings suggest that thyroid morphology screening should be performed in HD patients. PMID- 22299291 TI - The activity of mitochondrial superoxide dismutase in normal and pathological endometrium and correlation with the hormonal status of women. AB - GOAL: The goal of the study is to demonstrate the activity of superoxide dismutase mitochondria (MnSOD-e) in normal and pathologic endometrium and correlation of hormonal status of these cases with the MnSOD-e activity. MATERIALS AND METHODS: We analyzed 70 female patients, of which 30 of them had bleeding from the uterus (Group A) and 40 women had bleeding from the uterus, as well as a confirmed histopathological diagnosis of endometrial hyperplasia or endometrium carcinoma (Group B). In the follow-up we analyzed: age (respondents divided into five categories), parity (without pregnancy and multiple pregnancies), ultrasound (to determine whether there are pathological changes in the small pelvis), hormonal status of women (we took the blood of subjects to determine follicle stimulating hormone-FSH, luteinizing hormone-LH, progesterone Pr, estradiol-Es), histopathological analysis (the material was collected by exploratory curettage of normal and pathologically altered endometrium), determining the activity of antioxidant enzymes in the blood and endometrium (we determined the activity of MnSOD-e, whose activity was determined in normal and pathological endometrium). RESULTS: Within age groups dominated patients from 41 50 years, as well as multiple pregnancies. In the experimental group the mean results had lower values of the MnSOD enzyme in blood (0.93) and endometrium (1.94) as compared to the control group in blood (1.27), and endometrium (2.79). The MnSOD-e levels in the follicular phase was approximately at the same level in the experimental and control group, while the values in the luteal phase and stage of menopause was greater in control compared to the experimental group. MnSOD-e levels in endometrium in the follicular phase and stage of menopause were lower in experimental than in the control group, whereas in the luteal phase in the experimental group the value was higher than in the control group. CONCLUSIONS: On the basis of the results, which show a decrease in MnSOD activity both in the blood and endometrium of patients with hyperplasia and endometrium carcinoma we can see the importance of detecting activity of these enzymes in the diagnosis of the mentioned histological lesions, and therefore also possibilities of their application in clinical practice. PMID- 22299292 TI - Presenting colorectal carcinoma cases in our department. AB - BACKGROUND: Colorectal carcinoma is second commonest cancer causing death in Kosova. METHODOLOGY: In our study we present diagnostic methods, treatment, localization and laboratory findings in 155 patients, during 4 year period in patients with colorectal carcinomas treated in our clinic. RESULTS: Ninety four 94 (61.4%) of patients were male gender and 59 (38.6%) were female. Eritrosedimentation was elevated in 103 (67.3%) of patients, number of white blood cells was increased in 21 (7.2%) of patients and high level of glycemia is present in 11 (7.2%) of patients. The most involved age is from 41-50 years. The most common site of involvement was the rectum in 79 (51.6%), localization in sigma was in 37 (23.5%), the transverse colon in 21 (13.7%) of cases and the ascendant colon in 18 (11.1%) patients. Adenocarcinoma (98%) was the most common histiotype. CONCLUSION: We concluded, that all patients, especially with positive familial history must begin screening in age 40, during which colorectal carcinoma can be diagnosed in an early stage. PMID- 22299293 TI - Rate of complications and conversions after laparoscopic and open cholecystectomy. AB - BACKGROUND AND OBJECTIVES: Although many advantages of laparoscopic method in regard to open one have been already proved, both surgical methods may cause a certain number of complications. The goal of the study is to answer the question: Is Laparoscopic Cholecystectomy (LC) safer and more satisfactory method than open cholecystectomy (OC) concerning number, type and seriousness of complications? DESIGN AND SETTING: Prospective, the research includes all patients in Bihac Cantonal Hospital during 2007, who had cholecystectomy, laparoscopic or open, because of the gallbladder calculosus. METHODS: The study has included 476 patients who had cholecystectomy and who satisfied standards for this study. Of the total number of patients, 293 of them had laparoscopic cholecystectomy and 183 open cholecystectomy. Total number of complications is established for each group of patients. RESULTS: The study has shown that there were more complications in patients operated by open method than in those operated by laparoscopic cholecystectomy (p < 0.0001). Intraoperative bleeding was found in 1.63% of patients with open and 0.68% with laparoscopic cholecystectomy. Postoperative collection in abdomen were found in 2.18% of patients with open and 1.02% with laparoscopic method. The most common complications for open cholecystectomy were: infection (2.73%), hematoma in the wound (2.73%) and urine retention (2.18%). CONCLUSION: It can be concluded that LC and OC are comparable procedures for the treatment of gall stone disease in terms of complications, results of this study demonstrate that LC is essentially a safe procedure with low complicatins, morbidity and mortality rate. PMID- 22299294 TI - Attitude of the Macedonian intensivists regarding withdrawal of therapy in intensive care patients: curriculum for policy development. AB - Ethical confusion regarding withdraw of therapy led to the aim of the study in which the knowledge and attitude of the Macedonian Intensive Care Unit (ICU) doctors and their impact on decision making process were assessed. METHODS: Knowledge, Attitude and Practice (KAP) study has been conducted on a national sample of 217 ICU doctors (response rate 83.87%), applying restructured EURELD 2002 questionnaire as study instrument. CHI-square test was used for cross tabulations. RESULTS: 103 responders were females and 79 males with mean age 40, 2 years +/- 3 y. Significant percent of the doctors didn't know what is withdraw of therapy, chi-square 34.47 (p < 0.0001) and for most there was no difference between withdraw of therapy and euthanasia, chi-square 41.482 (p < 0.0001). Most of doctors didn't have any formal training (67%) and didn't know whether they had experience with withdraw or withhold. Similarly to other countries, for significantly higher percentage of the Macedonian intensivists patient's wishes and patient autonomy have to be main criteria for decision. Significantly higher group of doctors (p < 0.0001) would prefer to leave their own advanced directives. CONCLUSIONS: Legal principles in end of life care must be established in the country. Courts should have drawn a distinction between intentionally causing a patient's death (euthanasia) and allowing a patient to die as a result of the withdrawal of life support treatment. There is a need of additional improvement of postgraduate curriculum and continuous professional development of ICU doctors working with end-of-life patients. PMID- 22299295 TI - Localisation of war craniocerebral injury as risk factor for posttraumatic epilepsy. AB - AIM: To evaluate localization of certain zones of craniocerebral trauma and determine their importance for genesis ofposttraumatic epilepsy. PATIENTS AND METHODS: Study encompassed 50 war veterans, with craniocerebral trauma and posttraumatic epilepsy. Control group included 50 war veterans, with war craniocerebral injury who have not experienced epileptic seizures. The craniocerebral trauma zone in every patient was registered by computerized tomography (CT) of the brain at the Clinic for Radiology of the University Clinical Centre Tuzla. For statistical analysis it was used chi2 test. RESULTS: Average age in examinees' group was 29.92 (+/- 8.91); while in control group was 29.98 (+/- 9.97) (p > 0.05). Both, injury at several lobes and post-traumatic epilepsy were registered in 22 (44%) patients as well as in 8 (16%) patients in control group, which represents extra statistical significance (p < 0.05). Frontal lobe trauma in examinees' group had 7 (14%) patients and 15 (30%) patients in control group (p > 0.05). Temporal lobe trauma in examinees group had equal number of patients 6 in each (12%); parietal lobe injury was found in 14 (28%) patients with epilepsy and 11 (22%) patients without posttraumatic epilepsy (p > 0.05). Occipital lobe injury had one patient with posttraumatic epilepsy (2%) and 10 (20%) veterans in control group (p < 0.05). CONCLUSION: Trauma of several brain lobes at the same time increases the possibility of posttraumatic epilepsy. Trauma of certain brain lobes is not significant risk factor for posttraumatic epilepsy, but trauma of occipital lobe is significantly more represented in group of patients without posttraumatic epilepsy. PMID- 22299296 TI - Risperidone in the treatment of schizophrenia. AB - BACKGROUND: Risperidone is a second generation antipsychotic agent, with potent serotonin 5-HT2A and dopamine D2 receptor blocking effects. Specifically, risperidone possesses a unique balance of serotonin and dopamine antagonism, namely that its affinity for 5-HT2A receptors is significantly greater than its affinity for D2 receptors. Risperidone is well-established medication, with the proven effects on positive and negative symptoms of schizophrenia. The aim of research was to establish the effectiveness and safety of risperidone in patients with schizophrenia. SUBJECTS AND METHODS: The sample consisted of 60 subjects, age ranged was between 18-60 years, both genders, who met the criteria for the diagnosis various types of schizophrenia, according to ICD-10 (International Statistical Classification of Diseases). They were enrolled in the study as outpatient and inpatient setting. All subjects signed informed consent before entering into this study which had been conducted at the Psychiatric Clinic, University Clinical Center Sarajevo. Study was designed for 8-week, open-label, flexible-dose observational study. The subjects had to have a total score > -40 on Positive and Negative scale -two parts of the Positive and Negative Syndrome Scale (PANSS), and to be able to discontinue current antipsychotic medications. The primary efficacy parameter was the percent of score difference between baseline and week 8 of therapy on two above-mentioned PANSS subscales. The difference was considered as significant improvement if decrease from the baseline was 20% or more. The secondary efficacy parameter was subjective clinical evaluation of efficacy with five possible answers: very good, good, moderate, not satisfactory, not possible to evaluate. It was measured at the end of observational period by the investigator. RESULTS: All 60 enrolled patients completed the study. After the 8 weeks of treatment, 54/60 patients (90%) had clinically significant improvement of 20% or more decreased total PANSS score (Positive and Negative subscale). In 6/60 patients (10%) clinical improvement was also reported with less of 20% decreased total PANSS score. The side effects were registered in 8/60 patients (13.32%). The mild extrapyramidal symptoms registered in 1/60 (11.66%) patients, whom dose of risperidone was reduced. Increase of prolactine in 7/60 (11.66%), patients, whose dose of risperidone also were reduced. Average weight gain was 0.84 kg. CONCLUSION: In this study Risperidone has shown very good effectiveness and safety. PMID- 22299297 TI - Effect of anesthesia on the changes in the hormones levels during and after transvesical prostatectomy. AB - INTRODUCTION: Hypovolemia and pain are direct stimulators of hormonal response to trauma. Thus, neuroendocrine, metabolic and inflammatory aspects of the injury are part of an overall "stress response". In particular, it manifests in patients undergoing surgical intervention. These reactions can occur with trauma, burns, severe infections and physical exertion. Metabolic and neuroendocrine response to surgical intervention depends on several factors, such as severity and duration of the surgical trauma, patient's age, type of anesthesia and surgical techniques. GOAL: The aim of this study was to determine and evaluate levels of hormones in patients undergoing transvesical prostatectomy under general or local anesthesia: ACTH, PRL, TSH, T3, T4, cortisol, and to determine the influence of consciousness (in local-regional anesthesia) in relation to the unconscious state in the general balanced anesthesia on hormonal response measured values above mentioned levels of hormones. Determined the level of hormone values during three time periods: before anesthesia, during surgery in enucleation of prostate glandular tissue and 24 hours after surgery. PATIENTS AND METHODS: The study included a total of 100 patients from the Clinic of Urology, Clinical Center of Sarajevo who underwent surgery by technique oftransvesical prostatectomy. According to the criteria defined the subjects were divided into two test groups: Group I (n = 50)--patients underwent surgery under general anesthesia, Group II (n = 50)--patients underwent surgery in local-regional anesthesia. The first blood sample was taken at screening purposes just before the introduction of general anesthesia or loco regional anesthesia. The second sample was taken during surgery during enucleation of prostate gland tissue. A third blood sample was taken 24 hours after surgery. RESULTS: Increased levels of ACTH intraoperative in both anesthesia techniques applied, with a slightly larger increase in the value of the respondents with technique of general anesthesia. The values of ACTH after 24 hours showed a return to preoperative values in case of both techniques of anesthesia. Increased levels of PRL intraoperative in both anesthesia techniques applied, with larger peak values registered in patients under technique of general anesthesia (3554microIJ/L). High levels of PRL are maintained and postoperatively after 24 hours with both techniques applied anesthesia. Increased intraoperative levels of TSH in both anesthetic techniques, with higher maximum values in patients with technique of general anesthesia (7.20 mU/L). The values of TSH postoperatively after 24 hours showed a return to baseline in case of both applied technique of anesthesia. Low intraoperative values of T3 in both anesthetic techniques. Lower values of T3 are still continuing after 24 hours postoperatively in both applied techniques of anesthesia. The values of T4 hormone in subjects under general anesthesia did not show major deviations intraoperatively or postoperatively. CONCLUSIONS: Regional anesthesia with the present consciousness, but with sympathetic blockade caused a greater suppression of hormonal responses, than the general balanced anesthesia. PMID- 22299298 TI - Frequency of serological tests positive findings for celiac disease at the first relative of children with celiac disease. AB - GOAL: The research was undertaken with the aim to determine the frequency of positive findings of serological tests for celiac disease of the first relatives of children with celiac disease. MATERIALS AND METHODS: The study included 175 first relatives of 68 children suffering from celiac disease. Of that number, 75 (40 mothers and 26 fathers), 4 sisters and five brothers agreed to be tested for the presence of antibodies to celiac disease. For each subject were done tests on presence of anti-gliadin IgA, IgG antigliadin antibodies and IgA antibodies on tissue transglutaminase in the Polyclinic for Laboratory Diagnostics - Institute for Microbiology-Department of Immunology, University Clinical Centre (UCC) Tuzla. RESULTS: Of 175 first relatives of children with celiac disease 75 consented to serologic screening. Positive anti-gliadin IgG antibodies had 13.3%; anti-gliadin IgA antibodies had 2.6%, whereas antibodies on tissue transglutaminase were positive in 7.5% of respondents. With positive findings of anti-gliadin IgG were only two brothers. Fifteen subjects with positive findings of serological tests for celiac disease were confirmed by diagnosis of small bowel mucosal biopsy in 4%. CONCLUSION: In our study the incidence of positive serological tests for celiac disease among first relatives of children with celiac disease was 20%. All of our respondents with positive antibody findings had no symptoms that could indicate celiac disease. After establishing the diagnosis of celiac disease in children, it should be mentioned that testing must be done with the first relatives. This would, along with further diagnostic testing discover a significant number of asymptomatic patients and atypical forms of celiac disease. PMID- 22299299 TI - Financial aspects of the immunosuppressive therapy. AB - INTRODUCTION: In this study the authors have analyzed the costs associated with the immunosuppressive therapy in patients who underwent organ transplantation in two countries: the United States of America and Bosnia and Herzegovina (i.e. the entity Federation B&H). AIMS OF THE STUDY: The goal of this paper is to compare and contrast the costs of the immunosuppressive therapy in two countries against the total costs of the organ transplantation. Further, the costs, dosages and effectiveness of the particular types of immunosuppressant were also analyzed. Problem of the Study: Immunosuppressive medications are essential in preventing kidney transplant rejection. Most available pharmaco-economic information to date is for induction and maintenance therapies, while the data on the financial impacts of the rejection are still limited. Immunosuppressive regiments are expensive in the socio-economic environment of limited resources and constraints. MATERIAL AND METHODS: This academic article has utilized the publicly available sources of information from the Federation Entity of B&H, (i.e. Federal Department of Insurance and Reinsurance) in period 2006 to 2010, as well as peer reviewed academic articles, books, private and government data from the United States of America from 2006 to 2010, including projections for 2011. RESULTS: In the U.S. the cost of the immunosuppressive medications for the major types of organ transplantations typically range from US $19,300 to $34,600 per year based on commonly prescribed doses at average wholesale prices. In the Federation entity of B&H in 2009, the average cost per patient in F.B&H in 2010 was 6,009.00 KM (U.S.$4,292.00), which represents an absolute cost decrease of 740 KM or 11.00%, when compared to the higher average cost per patient in 2009, which was 6,749.00 KM (US $4,821.00). DISCUSSION: The process of finding the ideal medication regiments to minimize morbidity and mortality, while maximizing quality of life and optimizing the cost is the major challenge to the transplantation community. Pharmaco-economic analysis can provide valuable insight toward achieving of these, rather difficult goals. CONCLUSION: A sensitive pharmaco-economic analysis must be undertaken in order to achieve the best results in the world of limited/constrained resources and increasing demands for the expensive and quality of life improving immunosuppressive therapy in organ transplantation. PMID- 22299300 TI - Calcified right atrial and pulmonary artery mass after ventriculoatrial shunt insertion. AB - Insertion of ventriculoatrial (VA) shunts is an effective method of draining cerebrospinal fluid from the cerebral ventricle to the right atrium and significantly improves the survival of patients with hydrocephalus. Some patients who received a VA shunt subsequently developed complications, including thrombus formation around the intracardiac end of the catheter and thromboembolism. The relative rarity of complications and the long latency between shunt insertion and the development of symptoms in VA shunt recipients may result in misdiagnosis or delayed diagnosis. The case presented suggests that such patients may require routine echocardiography at regular intervals. Otherwise, the indwelling foreign body may become the source of a life-threatening thrombotic mass, if not recognised and treated appropriately. PMID- 22299301 TI - Report of one interesting case--unilateral kidney agenesis associated with ipsilateral kidney malrotation, anal atresia and pulmonary artery failure. AB - AIM: Renal agenesis is a fairly common congenital anomaly with an unknown definite etiology. Unilateral renal agenesis is much more common than bilateral renal agenesis, but it usually does not carry any major health consequence, as long as the other kidney is healthy. In some cases, renal agenesis may by associated with other congenital anomalies. We report a neonatal female patient born with unilateral renal agenesis associated with malrotation of ipsilateral kidney, anal atresia and pulmonary artery failure. MATERIAL AND METHODS: One month old female child was referred to Nuclear Medicine Department for dynamic renal scintigraphy which performed after intravenously injection of 0.5 mCi(99m) TcDTPA. Scintigraphy was carried out on a Dual Head-Siemens gamma camera using a high resolution collimator. During the dynamic scintigraphy patient was positioned in a supine position. Furosemide, as diuretic stimulator was administered intravenously at 18th minute of the study. RESULTS: The female patient, eight months old, with cough, short breath (dispnea), fatigue, nausea, vomiting and diarrhea was referred to DTPA renal scintigraphy. Symptoms were manifested ten days before patient had undergone the renal scintigraphy. During this time the patient was under pediatrics' control. A patient has undergone the biochemistry, ultrasound and radiologic examinations. Samples were isolated from the urine culture Pseudomonas aureginosa. The patient received antibiotics (Amikacin) for seven days, whereas last five days she received salbutamole and bisolvon. During physical examination we noticed a left abdominal stoma without palpation sensibility associated with an imperforate anus. From DTPA renal scintigraphy we found the absence of a right kidney, malrotation of a left kidney associated with seriously problems during the elimination of urine. DISCUSSION: Unilateral renal agenesis usually is without any major health consequences, but in cases where it is associated with other congenital malformations, such as malrotation of existing kidney, anal atresia and cardiopulmonary anomalies can be very serious problem for life. CONCLUSION: Dynamic renal scintigraphy is very highly sensitive and helpful method for detection of renal congenital malformations and function abnormalities. PMID- 22299302 TI - Scleroderma--from the aspect of dental medicine. AB - Modern etiopathogenic and diagnostic procedures of oral diseases are founded on molecular biology, genetic engineering, autoimmunity, pathohistological, cytological and immunofluorescence methods. The autoimmune processes may include the humoral and cellular immune responses and all organ systems may be involved. The systematic and orofacial manifestations of the scleroderma with medical and pathohistological documentation indicates to interdisciplinary cooperation in the treatment of such patients. The multidisciplinary approach in patients with scleroderma requires and suggests the most efficient prophylaxis treatment from the aspect of dental medicine. The systematic and orofacial manifestations of the scleroderma with medical and pathohistological documentation indicates to interdisciplinary cooperation in the treatment of such patients. The multidisciplinary approach in patients with scleroderma requires and suggests the most efficient prophylaxis treatment from the aspect of dental medicine. PMID- 22299303 TI - Laparoscopic transgastric gastrocystostomy pancreatic pseudocyst. AB - Article presents a laparoscopic cystogastrostomy of pancreatic pseudocysts. Pancreatic pseudocyst is a common complication of acute or chronic pancreatitis. It is treated by drainage. Until the development of laparoscopic method, the only surgical type of treatment was a drainage of pseudocyst into the stomach or intestine by the open surgery. In a recent years, a new procedures of laparoscopic treating of pseudocysts pancreatic were published. Despite of the small number of cases it is legible that this certain method of operative treatment has clear benefits for the patient. Herewith, we present a laparoscopic transgastric cystogastrostomy of the 44-year old woman who was admitted because of acute biliary pancreatitis. She was operated six months after the acute attack. PMID- 22299304 TI - Cheilitis granulomatosa. AB - Cheilitis granulomatosa is a rare disease characterised by the recurrent labial swelling of one or both lips with the possibility of the condition to remain on a permanent basis. The disease may appear independently or it may be linked to a paralysis such as the facial and lingua plicata which then characteristic of the Melcersson-Rosenthal Syndrome. The aim of this paper is to show a case of a patient with the granulomatosae cheilitis and lingua plicata whose reaction to the Chymoral Forte treatment was excellent. PMID- 22299305 TI - Terson's syndrome successfully treated with combined therapy. AB - PURPOSE: To present a case of Terson's syndrome consequent to ruptured intracranial aneurism treated successfully with a combined therapeutic approach. METHODS: Case report. A 37 year old man was urgently referred to the UCC Tuzla with sudden headache, vomiting and unconsciousness. CT scan showed ruptured aneurism of anterior communicant artery with signs of retinal thickening. Later ocular examination showed the massive bilateral vitreous haemorrhage. RESULTS: Patient was treated with medicamentous therapy for 7 months with no significant improvement. 7 months after aneurism rupture patient agreed to a surgical treatment. Right eye was treated surgically and left eye continued with conservative therapy. Visual acuity after vitrectomy improved in right eye to 1.0 and 0.5 in left eye. CONCLUSIONS: Terson's syndrome is relatively common complication of subarchnoid haemorrhage. Vitrectomy is safe and efficient approach to treat patients with Terson's syndrome. PMID- 22299306 TI - Congenital nephrotic syndrome. AB - The aim of this case is to present a case of a two month old female with congenital nephritic syndrome, which is very rare. On admission, the baby showed marked edema and distended abdomen. She was diagnosed and treated with daily albumin infusions, antibiotics, diuretic, gamma globulin replacement, ACEI and NSAIDs. Parents were informed about the nature of the disease, prognosis, and advised for further medical care in a more advanced kidney transplantation centre. This was the first treatment of this condition in the Pediatric Clinic in Kosovo and it presented a challenge for us. PMID- 22299307 TI - Initial experiences with propranolol treatment of infantile hemangiomas: report of three cases. AB - Infantile hemangiomas (IH) are common benign tumors in infancy, affecting 5-10% of all infants and they can still cause disfigurement and serious complications depending on their location and size, which can be associated with ulcerations and haemorrhage. Since 2008, propranolol has become the first choice of therapy for complicated IH, compared to conventional approach with systemic corticosteroid therapy as first-line treatment and then interferon or vincristine as second- or third-line therapeutic agents. We report three cases of hemangioma, successfully treated with propranolol. Oral propranolol was given for a period of 6 months with monthly follow up. All cases showed dramatic response without any relapse after stopping the treatment. Propranolol is novel and safe medication for treatment of infantile hemangioma. PMID- 22299308 TI - Congestion and sleep impairment in allergic rhinitis. AB - Allergic rhinitis is a disease with an increasing prevalence throughout the world that severely affects the quality of life of individuals suffering from it. Nasal congestion is the most common and bothersome symptom, and is often associated with sleep-disordered breathing, which is thought to be the reason for sleep impairment in individuals with rhinitis. The end result is a decrease in quality of life and productivity and an increase in daytime sleepiness. Treatment with intranasal corticosteroids has been shown to reduce nasal congestion. Data on sleep-related end points from clinical trials of intranasal corticosteroids indicate that this reduction is associated with improved sleep, reduced daytime fatigue, and improved quality of life. Other therapies, such as montelukast, also have a positive influence on congestion and sleep. This review examines nasal congestion and the associated sleep impairment of allergic rhinitis patients. It explores the adverse effects of disturbed sleep on quality of life and how these conditions can be reduced by therapies that decrease congestion. PMID- 22299309 TI - Clinical features of adult and pediatric anaphylaxis in Taiwan. AB - BACKGROUND: Most epidemiologic studies of anaphylaxis have been on Western populations, leaving the clinical and demographic pattern of this acute allergic condition in Asia unclear. OBJECTIVE: To investigate the clinical characteristics of patients with anaphylaxis in Chang Gung Memorial Hospital, the largest medical center in Taiwan. METHODS: We conducted a retrospective analysis of 201 patients who visited the emergency department or were admitted to the hospital for anaphylaxis from 2000 to 2010. We analyzed the causes, clinical presentation, and management, and also compared adult and pediatric cases. RESULTS: The average patient age was 43.3 years. Mortality from anaphylaxis was 0.5% (1/201). The annual number of cases presenting with anaphylaxis increased throughout the decade we studied. Seven types of etiology were identified: medication (53%), contrast medium (24%), idiopathic condition (8%), food (5%), blood transfusion (4%), insect sting (3%), and others (3%). Skin and respiratory presentations are more common in children than in adults (skin presentation, 81% vs. 51%, p = 0.002); respiratory presentation, 74% vs. 49%, p = 0.011), and cardiovascular presentation is more frequent in adults than in children (83% vs. 61%, p = 0.006). Clinical presentations with angioedema, gastro-intestinal and neurological system involvement, and management were not significantly different between adults and children. CONCLUSIONS: We conclude that anaphylaxis in Taiwan appears to be increasing, just as in the West, but shows a different clinical picture; medication rather than food was the most common cause of anaphylaxis in our population. Moreover, food-induced anaphylaxis in children is not so prevalent in Taiwan. PMID- 22299310 TI - Predictors of childhood food allergy: significance and implications. AB - BACKGROUND: Food allergy is common in children, and its occurrence is strongly associated with other allergies including anaphylaxis. Both genetic (e.g., CD14, STAT6, IL-10, SPINK5, and FOXP3 genes) and environmental (e.g., early exposure to highly allergic food) factors appear to contribute to food allergy. METHOD: Cross sectional study involved children in public primary schools in Al-Ain city (United Arab Emirates). 660 students from the chosen classes were provided with 35 questions to be answered by their parents with a response rate 60.2%. The objective of the study was to determine predictors for food allergy in children. RESULT: Significant associations were found between childhood food allergy and a history of personal allergy (atopic dermatitis, asthma or allergic rhino conjunctivitis) or immediate family members with food allergy or other allergic diseases. The best predictors for childhood food allergy were a personal history of asthma (p < 0.001), a personal history of atopic dermatitis (p < 0.001), a paternal history of atopic dermatitis (p = 0.005) and a paternal history of allergic rhino-conjunctivitis (p = 0.012). DISCUSSION: These results are consistent with the notion that "various forms of allergy, including childhood food allergy are hereditarily coupled". Thus, predicting childhood food allergy provides an opportunity to prevent or ameliorate the symptoms. PMID- 22299311 TI - Prevalence and clinical characteristics of adult-onset atopic dermatitis with positive skin prick testing to mites. AB - BACKGROUND: The clinical role of house dust mite (HDM) in atopic dermatitis (AD) is still controversial. OBJECTIVE: The aim of the study is to assess the prevalence, clinical relevance and characteristics of adult-onset AD patients with positive skin prick tests (SPT) to mites. METHODS: The case record forms of adult-onset AD patients who underwent SPT at the Skin Allergy Clinic, Siriraj Hospital were reviewed. RESULTS: Forty-one of 62 patients (66.1%) had positive SPT to mites. The frequency of intrinsic AD among adult-onset AD was 4.8% (3/62). SPT to HDM tended to be positive in patients who had personal or family history of atopy, positive SPT to several specific antigens or who presented with elevated serum IgE, chelitis, recurrent conjunctivitis and perifollicular accentuation, respectively. CONCLUSION The prevalence of adult-onset AD patients with mite sensitivity was high. There were some notable features that tended to be present in mite sensitive adult-onset AD patients. PMID- 22299312 TI - Type I hereditary angioedema in Taiwan -- clinical, biological features and genetic study. AB - BACKGROUND: Hereditary angioedema (HAE) is a rare, autosomal dominant inherited disease which is caused by a genetic deficiency of C1 esterase inhibitor (C1 INH). There have only been a few case reports in Taiwan to date. OBJECTIVE: To describe the clinical features of type I HAE in Taiwanese patients. METHODS: Three unrelated Taiwanese families with type I HAE are reported, and one case of a family from a review of PubMed was reviewed. Clinical manifestations, diagnostic examinations, management and genetic studies were analyzed. RESULTS: Including this report, 19 patients had low C1 INH and low C4 levels and were diagnosed with type I HAE. Only 11 (57.9%) patients were symptomatic. Recurrent skin swelling and edema over the four extremities or trunk were reported in all symptomatic patients (100%). 45.5% of the patients recalled laryngeal attacks and one patient died from asphyxia. 18.2% of the patients experienced abdominal symptoms. The age at the beginning of clinical symptoms ranged from 5 to 30 years (mean +/- SD: 20.82 +/- 7.88 years). The diagnosis tended to be delayed (range from 1 to 39 years; mean +/- SD: 8.45 +/- 11.04 years). Nine patients had a mutant C1 INH gene, and two patients received long-term prophylaxis with danazol. CONCLUSION: The prevalence of hereditary angioedema in Taiwan is low. Persons with low levels of C1 INH who were clinically symptomatic accounted for only 57.9% of the cases in our study, which is far lower than previous reports from other countries. Ethnic differences may be the reason for this finding. Further genomic studies are needed to elucidate the genetic penetrance of C1 INH deficiency in Taiwan. PMID- 22299313 TI - Immunoglobulin G (IgG) subclass deficiency in Thai children. AB - BACKGROUND: Patients with Immunoglobulin G (IgG) subclass deficiency may suffer from recurrent infections, mainly sino-pulmonary infection. OBJECTIVE: To determine the epidemiology of IgG subclass deficiency in Thai children at a tertiary care hospital and to compare the differences between children who were diagnosed with IgG subclass deficiency by using low level criteria [less than 2 standard deviation (SD) of normal levels for age] and by using low percentage criteria (proportion of each IgG subclasses/total IgG). METHODS: The study was a descriptive study of 55 children up to 15 years old with recurrent infections diagnosed as having IgG subclass deficiency but no acquired or other primary immune deficiencies except for IgA and/or IgM deficiency. RESULT: Isolated IgG3 subclass deficiency was the most common IgG subclass deficiency (56.4%). IgG3 subclass deficiency, either isolated or combined with other IgG subclass deficiency, was found in 85.5% of the cases. The common age of onset was between birth and five years of age. The most common presenting symptom was recurrent sinusitis (83.6%). Majority of the cases (89.3%) were diagnosed by low percentage criteria while 12.7% were diagnosed by low level criteria. All cases with low levels of IgG subclass antibodies also had low percentages. There were no statistically significant differences in the clinical manifestations and management methods between the children who were diagnosed by low level and low percentage. CONCLUSION: IgG3 subclass deficiency was the most common IgG subclass deficiency in Thai children. The most common presenting symptom was recurrent sinusitis. Although the diagnosis could be made in the patients with recurrent upper respiratory infection by using low level criteria, but the diagnosis should be considered when the low percentage criteria are met. PMID- 22299314 TI - Antiallergic effect of Ostericum koreanum root extract on ovalbumin-induced allergic rhinitis mouse model and mast cells. AB - OBJECTIVE: In the present study, the anti-allergic effect of OR extract was evaluated on an ovalbumin (OVA)-induced allergic rhinitis in mice and rat peritoneal mast cells (RPMC). METHODS: Balb/c mice were systemically sensitized to OVA followed by intraperitoneal and nasal allergen challenges. We investigated the effect of OR extract on allergic symptoms, serological marker production and histological changes of the nasal mucosa in a mouse model of allergic rhinitis. We observed mast cell degranulation and detected the production of histamine and inflammatory cytokines by ELISA. RESULTS: Compared to the OVA-control group, oral administration of OR extract at doses of 50 and 100 mg/kg significantly (p < 0.001) decreased the serum levels of histamine, OVA-specific IgE and Th2 cytokine,IIL-4 as well as increasing Th1 cytokine, IFN-gamma. Oral administration of OR extract also attenuated disease progression as determined by nasal symptoms and histological changes of the nasal mucosa in OVA-sensitized mice. Furthermore, treatment with OR extract at doses of 0.2, 0.5 ad 1 mg/mL in RPMC significantly (p <0.01, p <0.001 and p <0.001, respectively) decreased compound 48/80-induced histamine release and suppressed mast cell degranulation. Treatment with OR extract in RPMC also inhibited PMA/A23187-induced production of inflammatory cytokines such as TNF-alpha and IL-6. The mechanism of action underlying OR extract in allergic inflammation appears to be inhibition of the phosphorylation of ERK1/2 and p38 MAPK, in addition to blocking of the NFKB pathway. CONCLUSIONS: These results indicate that OR extract has the potential to be a source of antiallergic agents for use in allergen and/or mast cell-mediated diseases including allergic rhinitis. PMID- 22299315 TI - The difference in IL-1beta , MIP-1alpha, IL-8 and IL-18 production between the infection of PMA activated U937 cells with recombinant vaccinia viruses inserted 2004 H5N1 influenza HA genes and NS genes. AB - BACKGROUND: The severity of avian influenza H5N1 disease is correlated with the ability of the virus to induce an over production of proinflammatory cytokines from innate immune cells. However, the role of each virus gene is unknown. To elaborate the function of each virus gene, the recombinant vaccinia virus inserted HA and NS gene from the 2004 H5N1 virus were used in the study. METHODS: U937 cells and PMA activated U937 cells were infected with recombinant vaccinia virus inserted with HA or NS gene. The expressions of HA and NS proteins in cells were detected on immunofluorescence stained slides using a confocal microscope. The cytokine productions in the cell supernatant were quantitated by ELISA. RESULTS: The recombinant vaccinia virus inserted with HA genes induces the production of IL-1beta, MIP-1alpha, IL-8 and IL-18 cytokines from PMA activated U937 cells significantly more than cells infected with wild type vaccinia, whereas the recombinant vaccinia virus inserted with NS genes it was similar to that with the wild type vaccinia virus. However, there was no synergistic nor antagonistic effect of HA genes and NS genes in relation to cytokines production. CONCLUSION: Only the HA gene from the 2004 H5N1 virus induces IL-1beta, MIP lalpha, IL-8 and IL-18 cytokine productions from activated U937 cells. The same HA gene effect may or may not be the same in respiratory epithelial cells and this needs to be explored. PMID- 22299316 TI - Omalizumab treatment in severe adult atopic dermatitis. AB - Atopic dermatitis (AD) is one of the most common chronic skin diseases. Treatment options include lubricants, antihistamines, and corticosteroids in either topical or oral forms. Severe AD is frequently recalcitrant to these medications. We reported three cases of severe AD patients who had elevated of IgE levels and failed to response to several prior medical treatment. After being treated with Omalizumab (humanized monoclonal anti-IgE antibody), the patients had marked alleviation of symptoms with improved Eczema Area and Severity Index (EASI) and pruritic scores. No patient experienced adverse effect. PMID- 22299317 TI - A pediatric case of anaphylaxis due to octreotide. AB - Octreotide is an octapeptide that mimics natural somatostatin pharmacologically. It is a potent inhibitor of growth hormone, glucagon and insulin, which is used for treatment of acromegaly, symptomatic treatment of carsinoid tumours, and vasoactive intestinal peptide secreting tumors. It is also used for chylothorax, chemotherapy induced diarrhea and, as it inhibits the exocrine production of pancreatic enzymes, for acute and chronic pancreatitis. Gallbladder stones, diarrhea, nausea, vomiting, hypoglycemia/hyperglycemia, headache, and abdominal discomfort are some of the common adverse effects of octreotide and it may rarely cause anaphylaxis. We present here a child who had chronic pancreatitis and had an anaphylactic reaction to octreotide. To our knowledge this is the first pediatric case of anaphylaxis with octreotide who was successfully desensitized. PMID- 22299318 TI - Development of flow cytometry for detection and quantitation of red cell bound immunoglobulin G in autoimmune hemolytic anemia with negative direct Coombs test. AB - About 2-10% of patients with warm-antibody autoimmune hemolytic anemia (WAIHA) exhibit a negative direct Coombs test (DAT), requiring more sensitive tests, including detection of RBC-bound immunoglobulins by flow cytometry, for diagnosis. In this study, the optimal conditions for detection and quantitation of RBC-bound IgG by flow cytometry were studied using blood samples from six patients with AIHA and two healthy individuals. Quantitation of RBC-bound IgG was performed using quantum simply cellular (QSC) beads coated with goat anti-mouse IgG antibodies. For detection of RBC bound IgG, a 60-minute incubation of all blood samples with 40 microl of 1:10 dilution of FITC-conjugated mouse anti-human IgG gave mean fluorescent intensity (MFI) values comparable to experiments using larger amounts or higher concentrations of the anti-human IgG. The acquired antibody binding capacity (ABC) values (or IgG molecules) for each QSC bead level, at 40 microl of 1:5 and 1:10 dilution of anti-human IgG for 60 minutes were close to the manufacturer-assigned ABC values. The IgG molecules per RBC in all six patients with positive DAT of 4+, 3+, 2+, 1+, trace and negative DAT were 31,725, 3,823, 1,753, 524, 260 and 88 respectively and in two healthy individuals with negative DAT they were 104 and 78. PMID- 22299319 TI - Legislation and refusal of blood transfusion by a minor Jehovah-Witness in Belgium. AB - The refusal of blood transfusion by Jehovah's Witnesses in critical situations constitutes an ethical and juridical dilemma. The refusal to receive blood products by Jehovah's Witnesses is based on biblical verses. Recurring arguments to sustain this refusal regard the right to self-determination and the right to freedom of faith. If minors are involved, the problem is rendered even more difficult as the parental authority over young children needs to be taken into account. When adolescents are concerned, the situation if even more ambiguous since adolescents might be considered as mature enough to provide autonomous consent. On the basis of three cases, the most frequent bottlenecks that can come up in paediatric emergency services are highlighted: (1) the refusal of a blood transfusion by the parents of a young child; (2) the refusal by an adolescent and (3) prior refusal based on a "No Blood"-document. Regarding minors, the law on patients' rights in Belgium contains safety mechanisms concerning the preservation of physical integrity. Therefore, a key responsibility has been assigned to the physician. A step-by-step plan and a synoptic diagram are presented. PMID- 22299320 TI - Efficiency of infiltration with bupivacain after modified radical mastectomy. AB - BACKGROUND: Pre-incisional infiltration of anaesthetic is proven to reduce postoperative pain in breast cancer surgery. However, studies of post-incisional infiltration for modified radical mastectomy are rare. The purpose of this study was to investigate whether post-incisional infiltration with bupivacaine provides improved postoperative pain relief and a cost-effective benefit. METHODS: This is a retrospective study. Between January 2006 and May 2008, 139 patients who received modified radical mastectomy were recruited to participate in the study. Patients receiving local infiltration received bupivacaine (0.5% bupivacaine, 5 ml diluted to 10 ml with distilled water) injected into the dermis surrounding the incision after wound suture. Pain intensity was evaluated using a Visual Analogue Scale (VAS) score and measurement of the required doses of meperidine and acetaminophen. The pain score was recorded every eight hours for three days. RESULTS: All patients were female. Seventy-two patients received local infiltration with bupivacaine after wound suture and 67 patients did not. There were no significant differences between the two patient groups in age, body weight and height, length of general anaesthesia and operative time. Hospital stay was significantly shorter for patients receiving local infiltration of bupivacaine. The VAS score was higher up to 16 hours post-surgery for patients who did not receive local infiltration. Meperidine and acetaminophen consumption was less for patients who received local infiltration (P = 0.010). CONCLUSION: Post-incisional wound infiltration with bupivacaine can relieve pain during the first 16 hours after surgery and shorten hospital stay, and it provides a cost effective benefit. PMID- 22299321 TI - Carotid endarterectomy in a low volume vascular centre. AB - BACKGROUND: Carotid endarterectomy (CEA) is considered the golden standard of treatment for carotid artery disease in selected patients. METHODS: We studied retrospectively 246 CEAs performed in our centre from 2000-2008, and assessed the complications occurring during the first 30 days postoperatively. Surgical indications included symptomatic carotid stenosis > or = 60% and asymptomatic carotid stenosis > or = 75%. All patients underwent CEA with systematic use of a shunt, under general anesthesia. All arteriotomies were patched. All patients were transferred to ICU for 24 hours postoperatively. Mean hospital stay was 4.2 +/- 0.9 days. Ultrasound was performed 1 month postoperatively. RESULTS: Death, stroke, myocardial infarction (MI) and transient ischemic attack (TIA) were considered as major postoperative complications during the first 30 days after surgery. One death (0.4%), one nonfatal MI (0.4%) and two TIAs (0.81%) were recorded, while no stroke was present. CONCLUSIONS: We demonstrated that carotid endarterectomy can be safely performed in our low volume vascular centre. (246 CEAs in a nine year period). PMID- 22299322 TI - Laparoscopic retrieval of gossypibomas--short series and review of literature. AB - Laparoscopic removal of retained abdominal foreign bodies represents an obscure domain of minimally invasive surgery. Although not an infrequent situation in general surgical practice, there are very few papers presenting laparoscopic approache in these circumstances. An iatrogenic foreign body following surgery, is a serious complication that may lead to medico-legal problem. We present our experience and a literature review. METHODS: In the last 20 years 48 patients with abdominal foreign bodies were referred to us. Out of these four gossypibomas were managed laparoscopically. RESULTS: Retained swabs represent the most common iatrogenic abdominal foreign bodies. Removal of gossypiboma present more problems in laparoscopic environment due to encapsulation and difficulties in localisation, as retained swabs unusually display radio-opaque markings. There was one conversion due to dense adhesion to the gastric wall. Postoperative recovery was uneventful in all cases. CONCLUSIONS: Gossypibomas, among abdominal foreign bodies, represent a certain reality with significant legal implications. Prevention should prevail and all efforts should be made in such respect. Laparoscopic approach is possible in selected cases (small swabs, encapsulated, no complications). PMID- 22299323 TI - Revisiting the role of herniography in the preoperative work-up of groin hernias? AB - INTRODUCTION: The diagnosis of groin hernia is based on clinical symptoms and physical examination. In the case of equivocal clinical findings, patients are often referred for subsequent diagnostic imaging. Accurate detection is important to minimize the inherent risk of complications or to avoid unnecessary surgery. Although herniography has been reported as a save and highly accurate procedure, it has not gained widespread acceptance in the diagnostic work-up of groin hernias. METHODS: We retrospectively analysed 157 patients who underwent herniography in our department, which is to date the third largest study reporting on this technique. The diagnostic value of herniography was investigated--with laparascopic surgical findings serving as a gold standard--in comparison to clinical symptoms, physical examination and ultrasound. RESULTS: Herniography showed a substantial agreement with the surgical findings, but only a slight to fair agreement was found between surgery and clinical symptoms and examination. Poor agreement was found between sonographic and surgical findings. CONCLUSION: Based on the presented data and previously reported studies, we can conclude that herniography is a safe technique with a high accuracy to detect groin hernias in patients with equivocal clinical presentation, whereas ultrasound has a wide range in reported sensitivity. Clinicians and surgeons should take this into account when referring patients for subsequent imaging. PMID- 22299324 TI - Abdominal cystic lymphangiomas in pediatrics: surgical approach and outcomes. AB - BACKGROUND: Abdominal Cystic lymphangiomas (ACL) are uncommon benign masses usually presented during infancy. Although extremely rare, they may cause complications; therefore, the recommended therapy is surgical excision. The purpose of this study is to report our experience with the diagnosis and surgical treatment of ACL in pediatric population. MATERIAL AND METHODS: From January 1994 to December 2009, 10 patients (6 females; 4 males) with diagnostic confirmation of ACL were retrospectively included in study. Children's age ranged between 9 months and 8 years (mean age at diagnosis was 2.5 years). Clinical presentation, cyst location, imaging studies employed, surgical approach and pathologic features were analyzed. RESULTS: The most common symptom was abdominal pain but three cases were incidentally detected. One case had presented with acute abdomen after traumatic haemorrhage of the tumor. All patients were diagnosed with ultrasonography as first-line radiological study. MRI was used in last three cases. At surgery, concomitant bowel resection was necessary in 3 children. Location of the lesion (omentum, mesentery) did not influence the outcome but surgery was more difficult (operative time over three hours) in patients with lymphangioma affecting mesentery of the jejunum. Mean hospital stay after surgery was 6.7 days. Mean follow-up was 5.1 years. No recurrence of the cystic lymphangioma was noticed during follow-up. One case developed an intestinal occlusion due to bowel adhesions 1 year after surgery. CONCLUSIONS: ACL usually affect infants and young children and may present with spectrum of symptoms from an incidental finding to an acute life-threatening abdominal obstruction. Complete excision of the tumor is a safe and effective method in the management of ACL in pediatric population. Surgery is mandatory to avoid potential complications. PMID- 22299325 TI - Complicated sigmoid diverticulitis--Hartmann's procedure or primary anastomosis? AB - INTRODUCTION: Diverticular disease of the colon is a common condition in developed countries. For perforated diverticulitis Hartmann's procedure is a safe and quick treatment option. But intestinal restoration needs further interventions. This leads to high complication rates and cost. Therefore a critical evaluation of surgical treatment options is necessary. METHODS: During a period of 18 months 88 patients underwent surgical resection for diverticulitis. Forty patients had emergency surgery. Among those a primary anastomosis was performed in 21 patients. The other 19 patients had interval colostomy. Among 21 patients with primary anastomosis major complications occurred in two patients, vs. twelve in patients with Hartmann's operation (p = 0.03). In the Hartmann group eight patients had major general complications, vs. one patient in the group with primary anastomosis (p = 0.06). The mean hospital stay was 38 days after Hartmann's procedure, vs. 13 days for patients with primary anastomosis (p < 0.01). CONCLUSION: In emergency surgery for complicated diverticulitis primary anastomosis is not associated with an increased postoperative morbidity. A primary anastomosis reduces the need for further surgical interventions and complex re-operations. Thus, an overall reduction of morbidity, cost, complication rate and hospital stay is possible. Therefore this technique is advantageous for patients and hospitals. PMID- 22299326 TI - The surgical history of the amputated limb according to the indication for revascularization: diabetic foot, acute ischaemia, aneurysmal disease, chronic arterial occlusive disease. AB - BACKGROUND: To investigate whether the indication for the first revascularization (diabetic foot, acute ischaemia, aneurysmal disease, chronic occlusive disease) determines the surgical history and survival time in amputated limbs. METHODS: The surgical history of lower extremities amputated between 2002 and 2009 was reviewed for the number of (endo)vascular procedures, minor amputations, wound debridements, complications requiring surgery (acute ischaemia, bleeding, graft infection) and limb survival time (LST). RESULTS: 100 limbs were included in the study. The four groups underwent a similar number of surgical procedures (mean 4.1). Diabetic foot limbs had fewer revascularizations (mean 1.3, p = 0.003) and complications (mean 0.1, p = 0.005), but more minor amputations and wound debridements (mean 1.3, p = 0.002), in a significantly shorter LST (mean 555 days, p = 0.003). Acute ischaemic limbs showed the shortest LST (mean 179 days, p = 0.003) and significantly more complications (mean 0.8, p = 0.005). Limbs initially treated for aneurysmal disease or chronic occlusive disease had the highest number of revascularizations (mean resp. 2.7 and 2.6) and the longest LST (mean resp. 1669 and 1459 days, p = 0.001). Limbs with advanced chronic occlusive disease (rest pain or gangrene) presented with fewer revascularisations (mean resp. 2.5 and 1.8, p = 0.01) and a shorter LST (mean resp. 1284 and 794 days, p = 0.004) compared to claudicants. CONCLUSIONS: Our study suggests that the surgical history and limb survival in amputated limbs is disease and stage specific, and determined by the indication of the first revascularisation. PMID- 22299327 TI - TNM-classification for lung cancer: from the 7th to the 8th edition. AB - Most tumors are staged according to the Tumor-Node-Metastasis (TNM) classification. For lung cancer a new edition was introduced in 2009 and generally applied since 2010. This 7th TNM-classification is based on a large, international retrospective database. Important changes were made regarding the T, N, M factors and specific subcategories were added. However, this 7th edition is still purely based on anatomical information. Other prognosticators such as laboratory results, histology, tumor markers and molecular genetic factors are not yet considered. To prepare the 8th TNM classification a prospective database developed by the International Association for the Study of Lung Cancer (IASLC), is currently enrolling patients from all continents. In this way, more precise and reliable data will become available on specific subdivisions of the T, N and M factors. If proven to be prognostically valid, other parameters will be included as histology, demographic data and specific biochemical and molecular predictive and prognostic factors. All centers with a large experience in thoracic oncology are encouraged to participate in this prospective database. PMID- 22299328 TI - MR imaging of fistula in ano: indications and contribution to surgical assessment. AB - BACKGROUND: Magnetic Resonance Imaging (MRI) is the imaging modality of choice for fistula in ano. The purpose of this study was to analyse the use of MRI, and to assess its contribution towards the assessment of this sometimes difficult condition. METHODS: A retrospective analysis of all patients with fistula in ano between January 2003 and December 2007 was performed, focussing on those who had MRI assessment. The primary pathology, indication for MRI and the contribution of this investigation to assessment of fistula in ano were analysed. RESULTS: MRI was performed in 40 patients. The primary pathologies included: perianal sepsis in 20 (50%), Crohn's disease in 11 (27.5%), primary fistula in ano in 6 (15%) and others in 3 (7.5%) patients. Indications for MRI were to assess the fistula anatomy in 17 (42.5%), to assess a clinically suspected fistula in 12 (30%), to assess a complex fistula found at Examination Under Anaesthesia (EUA) in 6 (15%) and to exclude a fistula in 5 (12.5%). MRI was considered helpful in 34 (85%) of all cases. MRI established the fistula anatomy and guided further surgery in 47.1%, correlated with EUA findings in 38.2% and excluded a suspected fistula in 14.7% of these. CONCLUSIONS: This study further supports the benefit of using MRI to assess fistula in ano. When used in selected patients, it was of benefit in 85% of cases, by establishing fistula anatomy and guiding further surgery, correlating EUA findings or excluding a clinically suspected fistula. PMID- 22299329 TI - Acute abdominal pain: the importance of genital examination. AB - Torsion of an intra-abdominal testis is a rare cause of acute abdominal pain. The purpose of this report is to highlight a case of torsion of an abdominal testis in a patient with an unusual clinical presentation, with the fortuitous diagnosis of a "carcinoma in situ" and to emphasize the role of routine genital examination when investigating patients with abdominal pain. PMID- 22299330 TI - Pseudoaneurysm of the hepatic artery and hemobilia: a rare complication of laparoscopic cholecystectomy; clinical case and literature review. AB - Laparoscopic cholecystectomy is the Gold Standard for the treatment of symptomatic cholelithiasis. There is still an increase in the rate of incidence of biliary and vascular injuries with laparoscopy. Hepatic artery pseudoaneurysm is a rare but serious complication associated with laparoscopic cholecystectomy and bile duct injury. The diagnosis may be difficult. Our experience of a case of iatrogenic lesion of the right hepatic artery with the formation of pseudoaneurysm treated by means of embolization of the artery is presented here. PMID- 22299331 TI - Successful treatment for a large renal cell carcinoma with tumour thrombus. AB - We report the case of a 41-year-old man with symptoms of exertional dyspnoea and easy fatigue. Physical examination revealed a palpable mass with knocking pain over the right flank region and a cardiac murmur with jugular vein engorgement. Transoesophageal echocardiography revealed a right atrial mass that caused tricuspid inflow obstruction. Computed tomography revealed a giant mass (approximately 15 x 15 cm2) in the right kidney; this finding was consistent with renal cell carcinoma. Despite the metastatic status, right nephrectomy was performed and the intra-atrial tumour thrombus (TT) was resected under a cardiopulmonary bypass in order to relieve the tricuspid obstruction. Histological examination confirmed renal cell carcinoma with TT. The patient is healthy with satisfactory systolic function at 1-year follow-up. PMID- 22299332 TI - Trocar site herniation of the small bowel after laparoscopic bilateral adnexectomy despite fascial closure: a case report. AB - In this paper we report a case of an incarcerated hernia occurring through the peritoneal and muscular defect caused by a previous trocar insertion. The patient developed the hernia eight days after bilateral laparoscopic adnexectomy and presented small bowel obstruction signs. This hernia occurred despite correct closure of the internal oblique fascia. The patient was re-operated and exploratory laparoscopy confirmed the diagnosis. The hernia was reduced via a small extension of the previous incision, and the defect was repaired by separated stitches. This case shows that a trocar site hernia can appear despite correct closure of the fascia, which is poorly described except for obese patients. It suggests the need for careful closure of the abdominal wall including the peritoneum after a laparoscopic procedure. Trocar site hernia has to be considered in cases of post laparoscopic small bowel obstruction. We reviewed the literature and found no randomized control study concerning this problem: only reviews, retrospective studies, case reports and technical notes. These papers are discussed and compared with our case. PMID- 22299333 TI - Pseudoaneurysm of the anterior tibial artery: a complication of ankle arthroscopy. AB - The authors describe a case of pseudoaneurysm of the anterior tibial artery after ankle arthroscopy that was undiagnosed for more then 10 weeks. The pseudoaneurysm was resected and postoperative recovery was uneventful. Anterior tibial artery pseudoaneurysm is a rare complication of ankle arthroscopy and should be considered when a patient presents with a local swelling of the anterolateral ankle joint. PMID- 22299334 TI - The reason for recess. Children who are more physically active may do better in school. PMID- 22299335 TI - Species displacements are common to two invasive species of leafminer fly in China, Japan, and the United States. AB - Under field conditions, species displacements have occurred in different directions between the same invasive species of leafminers (Diptera: Agromyzidae). Liriomyza sativae (Blanchard) was displaced by L. trifolii (Burgess) in the western United States, with evidence suggesting that lower insecticide susceptibility of L. trifolii is a factor. However, in Japan, the opposite has occurred, as L. trifolii was recently displaced by L. sativae. This displacement is probably because of the higher fecundity of L. sativae and differential effects of parasitoids on the two leafminer species. Here, we carried out long-term surveys of these same two invasive leafminer species during January through March in 1999, 2007, and 2011, as well as June through July in 2011, in eight locations (Sanya, Dongfang, Haikou, Leidong, Lingshui, Wuzhisan, Qionghai, and Danzhou) across Hainan Island of southern China. Our results indicate that, between 2007 and 2011, L. trifolii rapidly replaced L. sativae as the predominant leafminer of vegetables on Hainan Island, similar to the situation in the western United States. Further surveys of growers revealed that avermectins and cyromazine are the two most frequently used insecticides against leafminers on Hainan Island. Dose-mortality tests showed that L. trifolii populations from Hainan Island are less susceptible to avermectins and cyromazine compared with L. sativae populations. This lower insecticide susceptibility of L. trifolii may be associated with the displacement of L. sativae by L. trifolii, although additional ecological or environmental factors cannot be ruled out. PMID- 22299336 TI - Laboratory study on the effects of temperature and three ventilation rates on infestations of Varroa destructor in clusters of honey bees (Hymenoptera: Apidae). AB - In this study, reduced levels of ventilation were applied to small clusters of bees under controlled conditions to determine whether lowered ventilation rates and the resulting increased levels of CO2 could increase the mortality rates of varroa. Two experiments were performed at two different temperatures (10 degrees C and 25 degrees C). Both experiments compared varroa mortality among high (360 liters/h), medium (42.5 liters/h), and low (14 liters/h) rates of ventilation. The clusters of bees (approximately 300 worker bees) in bioassay cages with 40 introduced varroa mites were placed into self-contained glass chambers and were randomly assigned to one of the three ventilation treatments within incubators set at either of the two temperatures. Bee and varroa mortality and the levels of CO2 concentration were measured in each of the experimental chambers. In both experiments, CO2 levels within the chamber increased, with a decrease in ventilation with CO2 reaching a maximum of 1.2 +/- 0.45% at 10 degrees C and 2.13 +/- 0.2% at 25 degrees C under low ventilation. At high ventilation rates, CO2 concentration in chamber air was similar at 10 degrees C (1.1 +/- 1.5%) and 25 degrees C (1.9 +/- 1.1%). Both humidity and CO2 concentration were higher at 25 degrees C than at 10 degrees C. Bee mortality was similar within all ventilation rate treatments at either 10 degrees C (11.5 +/- 2.7-19.3 +/- 3.8%) or 25 degrees C (15.2 +/- 1.9-20.7 +/- 3.5%). At 10 degrees C, varroa mortality (percentage dead) was greatest in the high ventilation treatment (12.2 +/- 2.1%), but only slightly higher than under low (3.7 +/- 1.7%) and medium ventilation (4.9 +/- 1.6%). At 25 degrees C, varroa mortality was greatest under low ventilation at 46.12 +/- 7.7% and significantly greater than at either medium (29.7 +/- 7.4%) or low ventilation (9.5 +/- 1.6.1%). This study demonstrates that at 25 degrees C, restricted ventilation, resulting in high levels of CO2 in the surrounding environment of small clusters of honey bees, has the potential to substantially increase varroa mortality. PMID- 22299337 TI - Effects of liberibacter-infective Bactericera cockerelli (Hemiptera: Triozidae) density on zebra chip potato disease incidence, potato yield, and tuber processing quality. AB - In plant pathosystems involving insect vectors, disease spread, incidence, and severity often depend on the density of the vector population and its rate of infectivity with the disease pathogen. The potato psyllid, Bactericera cockerelli (Sulc), has recently been associated with zebra chip (ZC), an emerging and economically important disease of potato in the United States, Mexico, Central America, and New Zealand. "Candidatus Liberibacter solanacearum," a previously undescribed species of liberibacter has been linked to the disease and is transmitted to potato by B. cockerelli. Experiments were conducted under laboratory and field conditions to determine the impact of B. cockerelli density on ZC incidence, potato yield, and tuber processing quality. Insect densities ranging from one to 25 liberibacter-infective psyllids per plant were used during the experiments. Results showed that a single adult potato psyllid was capable of inoculating liberibacter to potato and causing ZC disease after a 72-h inoculation access period and was as damaging as 25 psyllids per plant. In addition, ZC-diseased plants showed a sharp reduction in tuber yield but the disease response was independent of the density of psyllids. Furthermore, both glucose and sucrose were found to have highly elevated concentrations in ZC diseased potato tubers compared with noninfected ones and psyllid density did not vary the response. The high reducing sugar concentrations found in ZC-infected potato tubers are believed to be responsible for browning and reduced quality in processed ZC-infected tubers. This information could help ZC-affected potato producers in making effective management decisions for this serious disease. PMID- 22299338 TI - Exitianus obscurinervis (Hemiptera: Cicadellidae), a new experimental vector of Spiroplasma kunkelii. AB - "Corn stunt" caused by the mollicute Spiroplasma kunkelii (Whitcomb) is potentially one of the most severe diseases affecting the corn (Zea mays L.) crop in the Americas, and the leafhopper Dalbulus maidis (DeLong & Wolcott) is considered its most important vector. However, other insects seen quite frequently in corn crops might well be its vectors in Argentina To identify any leafhoppers species other than D. maidis that can transmit S. kunkelii, transmission assays were conducted, using individuals of Exitianus obscurinervis (Stal) collected in field and reared under controlled conditions. S. kunkelii was transmitted to corn plants by E. obscurinervis. The pathogen was transmitted to seven of the 11 plants, which showed characteristic corn stunt symptoms, and the presence of the pathogen was confirmed by DAS-ELISA. The presence of S. kunkelii in the E. obscurinervis individuals used in transmission experiments was confirmed by polymerase chain reaction and electron microscopy. The current study shows the existence of a new experimental vector of S. kunkelii, the leafhopper E. obscurinervis, which acquired spiroplasmas from infected plants and inoculated it to healthy plants. PMID- 22299339 TI - Detection and variability of aster yellows phytoplasma titer in its insect vector, Macrosteles quadrilineatus (Hemiptera: Cicadellidae). AB - The aster yellows phytoplasma (AYp) is transmitted by the aster leafhopper, Macrosteles quadrilineatus Forbes, in a persistent and propagative manner. To study AYp replication and examine the variability of AYp titer in individual aster leafhoppers, we developed a quantitative real-time polymerase chain reaction assay to measure AYp concentration in insect DNA extracts. Absolute quantification of AYp DNA was achieved by comparing the amplification of unknown amounts of an AYp target gene sequence, elongation factor TU (tuf), from whole insect DNA extractions, to the amplification of a dilution series containing known quantities of the tuf gene sequence cloned into a plasmid. The capabilities and limitations of this method were assessed by conducting time course experiments that varied the incubation time of AYp in the aster leafhopper from 0 to 9 d after a 48 h acquisition access period on an AYp-infected plant. Average AYp titer was measured in 107 aster leafhoppers and, expressed as Log10 (copies/insect), ranged from 3.53 (+/- 0.07) to 6.26 (+/- 0.11) occurring at one and 7 d after the acquisition access period. AYp titers per insect and relative to an aster leafhopper chromosomal reference gene, cp6 wingless (cp6), increased approximately 100-fold in insects that acquired the AYp. High quantification cycle values obtained for aster leafhoppers not exposed to an AYp-infected plant were interpreted as background and used to define a limit of detection for the quantitative real-time polymerase chain reaction assay. This method will improve our ability to study biological factors governing AYp replication in the aster leafhopper and determine if AYp titer is associated with frequency of transmission. PMID- 22299340 TI - Coffee husk waste for fermentation production of mosquitocidal bacteria. AB - Coffee husk waste (CHW) discarded as bio-organic waste, from coffee industries, is rich in carbohydrates. The current study emphasizes the management of solid waste from agro-industrial residues for the production of biopesticides (Bacillus sphaericus, and B. thuringiensis subsp. israelensis), to control disease transmitting mosquito vectors. An experimental culture medium was prepared by extracting the filtrates from coffee husk. A conventional culture medium (NYSM) also was prepared. The studies revealed that the quantity of mosquitocidal toxins produced from CHW is at par with NYSM. The bacteria produced in these media, were bioassayed against mosquito vectors (Culex quinquefasciatus, Anopheles stephensi, and Aedes aegypti) and it was found that the toxic effect was statistically comparable. Cost-effective analysis have revealed that, production of biopesticides from CHW is highly economical. Therefore, the utilization of CHW provides dual benefits of effective utilization of environmental waste and efficient production of mosquitocidal toxins. PMID- 22299341 TI - Impacts of thiamethoxam seed treatment and host plant resistance on the soybean aphid fungal pathogen, Pandora neoaphidis. AB - Since the introduction of soybean aphid, Aphis glycines Matsumura, from Asia, insecticide use in soybean has increased substantially in the north central United States. Insecticide seed treatments and aphid resistant soybean varieties are management tactics that may reduce reliance on foliar applications of broad spectrum insecticides. Exploring potential nontarget impacts of these technologies will be an important step in incorporating them into aphid management programs. We investigated impacts of thiamethoxam seed treatment and Rag1 aphid resistant soybean on a fungal pathogen of soybean aphid, Pandora neoaphidis (Remaudiere & Hennebert) Humber, via open plot and cage studies. We found that although thiamethoxam seed treatment did significantly lower aphid pressure in open plots compared with an untreated control, this reduction in aphid density translated into nonsignificant decreases in fungal disease prevalence in aphids. Furthermore, when aphid densities were approximately equal in seed treated and untreated soybean, no impact on aphid fungal disease was observed. In open plots, Rag1 resistant soybean experienced lower aphid pressure and aphid disease prevalence compared with a nonresistant isoline. However, in cages when aphid densities were equivalent in both resistant and susceptible soybean, resistance had no impact on aphid disease prevalence. The addition of thiamethoxam seed treatment to resistant soybean yielded aphid densities and aphid disease prevalence similar to untreated, resistant soybean. These studies provide evidence that thiamethoxam seed treatments and Rag1 resistance can impact P. neoaphidis via decreased aphid densities; however, this impact is minimal, implying use of seed treatments and host plant resistance are compatible with P. neoaphidis. PMID- 22299342 TI - Refrigerated eggs of Riptortus pedestris (Hemiptera: Alydidae) added to aggregation pheromone traps increase field parasitism in soybean. AB - Riptortus pedestris (F.) (Hemiptera: Alydidae) is a key pest of soybean [Glycine max (L.) Merr.] in Korea and Japan. Aggregation pheromone traps have been used to attract R. pedestris. An aggregation pheromone, produced by males of R. pedestris, also attracts the egg parasitoid, Ooencyrtus nezarae Ishii (Hymenoptera: Encyrtidae). As a new method of pest management, we propose the use of nonviable host eggs in the pheromone trap together to both trap R. pedestris and propagate parasitoids on host eggs attached to the trap. Approximately ten thousand nonviable refrigerated host eggs were placed outside pheromone traps in three soybean fields (0.167-0.284 ha.). During the sampling period from 7 August to 8 October in 2008, statistical significance of treatment was not found in any life stage of R. pedestris population. However, significantly higher parasitism of both natural (78-91%) and refrigerated eggs (36-59%) occurred in the treatment sites, compared with control sites where parasitism was 0-62% and 16-34% on natural and refrigerated eggs, respectively. The proportion of bean pods with stink bug feeding damage was significantly reduced by 47% in the treatment sites. This study is the first trial of an integrated pest management (IPM) strategy using both nonviable host eggs and trap that simultaneously targets both the pest and its natural enemy. PMID- 22299343 TI - Effect of larval density and host species on preimaginal development of Bactrocera tau (Diptera: Tephritidae). AB - The fruit fly, Bactrocera tau (Walker) (Diptera: Tephritidae), is an important pest of fruit and vegetable crops. In this study, host preference of B. tau females and the effects of host species and larval density on larval survival, pupal weight, adult emergence, and developmental duration were investigated on cucumber (Cucumis sativus L.), sponge gourd (Luffa cylindrical L. (Roem)), bitter gourd [Momordica charantia (Cucurbitaceae) L.], guava [Psidium guajava (Myrtaceae) L.], and tangerine [Citrus reticulata (Rutaceae) (Blanco)]. The results showed that females preferred to cucumber over other host species. Larval feeding experience affected subsequent host oviposition preference of adult females. Host species and initial larval density affected certain aspects of the biology of B. tau. Larval density negatively affected insect performance. Survival rates at low densities were significantly higher than that at high densities. Total developmental duration reduced at high larval densities. Cucumber was more suitable to larval growth. Larvae on cucumber grew faster and the puparia were heavier than that on other host species. Larval survival, pupation rate and adult emergence were higher on cucumber compared with those in other host species. Oviposition preference of adult females was correlated with performance of their offspring. PMID- 22299344 TI - Phytosanitary irradiation of Liriomyza trifolii (Diptera: Agromyzidae). AB - Agromyzid leafminers are economic and quarantine pests of a variety of vegetables, flowers, and ornamental foliage. Methyl bromide fumigation is often used as a phytosanitary treatment when quarantined agromyzids are found in shipped commodities; alternative treatments are sought. Ionizing radiation is a viable alternative that is increasing in use worldwide. A dose of 400 Gy is accepted by USDA-APHIS for all insects (except Lepidoptera pupae and adults) on all commodities. Efforts to lower this dose and make it acceptable to other countries involve determining radiotolerance of families of major quarantine pests. Agromyzidae is one such family for which no useful information on radiotolerance exists. This research sought to determine the dose required to control a major agromyzid pest, Liriomyza trifolii (Burgess) and was performed on L. trifolii collected in Weslaco, TX, reared on Phaseolus vulgaris L. and Capsicum annuum L. and irradiated in the late puparial stage. The measure of efficacy was prevention of F1 mine formation. Puparia collected from Gossypium hirsutum L. and reared on P. vulgaris were more radiotolerant than those collected and reared on C. annuum. A dose of 214 Gy may prevent F1 mine formation of L. trifolii. This research used a variation of probit analysis where the direct response of the treated individual is not measured, but the response of the F1 generation is. This type of analysis is useful in phytosanitary irradiation research where the measure of efficacy often involves a response of the F1 generation. PMID- 22299345 TI - Response of female Ceratitis capitata (Diptera: Tephritidae) to a spinosad bait and polymer matrix mixture with extended residual effect in Hawaii. AB - The effectiveness of foliar applications of protein baits against pestiferous fruit flies (Tephritidae) can be adversely affected by a rapid loss of attractive volatile compounds and by rainfall due to the high water solubility of the baits. In a large coffee, Coffea arabica L., plantation in Hawaii with high and low populations of Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), the relative attractiveness of GF-120 NF Naturalyte Fruit Fly Bait as either a 40% (vol:vol) spray solution (= GF-120 NF) or as a formulated proprietary amorphous polymer matrix (= GF-120 APM) was compared. The GF-120 APM formulations contained either, 25, 50, or 75% of GF-120 NF (wt:wt). All baits were tested in association with visually attractive yellow bait stations as a way of standardizing the evaluations. With both high and low C. capitata populations, significantly more females were attracted to the fresh sprayed GF-120 NF than to any of the three fresh GF-120 APM formulations. The attractiveness of GF-120 sprayed decreased significantly after 1 wk, whereas 1-wk-old GF-120 APM formulations were as attractive as similar fresh formulations. GF-120 APM 75% aged for 3 wk outperformed similarly-aged sprayed GF-120 NF with comparatively high C. capitata populations. With low populations, both GF-120 APM 75% and GF 120 APM 50% aged for 2 wk outperformed the similarly aged sprayed GF-120 NF. Combined findings indicate that APM mixed with either 50 or 75% GF-120 applied to bait stations can be attractive to female C. capitata for up to 3 wk longer than the standard sprayed GF-120 NF. PMID- 22299346 TI - Effects of temperature on the life history parameters and population growth rates of Hyalopterus pruni (Hemiptera: Aphididae). AB - The mealy plum aphid, Hyalopterus pruni (Geoffroy) (Hemiptera: Aphididae) is a pest of prune trees in California. The impact of aphids as pests is well characterized by their population growth rate, a parameter integrating their age specific development, survivorship, and fecundity. These population parameters were measured at five constants temperatures on potted prune trees. Development rates increased with temperature up to an optimum. The relationship between development rate and temperature was described by linear and nonlinear models. Developmental threshold temperature was greater for the nonlinear model than for the linear model. Thermal requirement for development and maximum lethal temperature determined by these models were similar to those for other aphids. The greatest proportional survivorship of nymphs occurred at 26 degrees C. Mean daily fecundity was lowest at 14 degrees C and highest at 22 degrees C. Adult longevity decreased with temperature. Population growth rates for H. pruni were estimated from measurements of fecundity and development time and were highest at 22 degrees C. This is the first study to document the temperature dependence of the life history parameters for H. pruni and the first to generate a degree-day model for the prediction of phenological events. PMID- 22299347 TI - Developmental database for phenology models: related insect and mite species have similar thermal requirements. AB - Two values of thermal requirements, the lower developmental threshold (LDT), that is, the temperature at which development ceases, and the sum of effective temperatures, that is, day degrees above the LDT control the development of ectotherms and are used in phenology models to predict time at which the development of individual stages of a species will be completed. To assist in the rapid development of phenology models, we merged a previously published database of thermal requirements for insects, gathered by online search in CAB Abstracts, with independently collected data for insects and mites from original studies. The merged database comprises developmental times at various constant temperatures on 1,054 insect and mite species, many of them in several populations, mostly pests and their natural enemies, from all over the world. We show that closely related species share similar thermal requirements and therefore, for a species with unknown thermal requirements, the value of LDT and sum of effective temperatures of its most related species from the database can be used. PMID- 22299348 TI - Influence of pymetrozine on feeding behaviors of three rice planthoppers and a rice leafhopper using electrical penetration graphs. AB - Pymetrozine reportedly inhibits feeding of plant sap-sucking insects, such as aphids and brown planthopper (Nilaparvata lugens (Stal)). By using electrical penetration graph (EPG), this study was conducted to investigate any differential effect of pymetrozine on the feeding behaviors of four major rice sap-sucking insect species, 1) N. lugens, 2) white-backed planthopper (Sogatella furcifera (Horvath)), 3) small brown planthopper (Laodelphax striatellus (Fallen)), and 4) green rice leafhopper (Nephotettix cincticeps Uhler). On pymetrozine-free TN1 rice plants, white-backed planthopper and small brown planthopper showed a significantly less activity in the phloem phases than brown planthopper or green rice leafhopper while green rice leafhopper engaged in relatively more xylem ingestion than brown planthopper, white-backed planthopper, and small brown planthopper. On the plants treated with 100 mg liter(-1) of pymetrozine, all four insect species showed significant increases, in total duration of nonprobing and significant decreases in the activities in phloem tissue, while all species showed similar feeding behavior during the pathway and xylem phases. This study revealed that, regardless of whether the insects on untreated plants spent more time feeding on phloem than xylem (brown planthopper) or more time on xylem than phloem (green rice leafhopper) or similar times on phloem and xylem (white-backed planthopper and small brown planthopper), their feeding behavior was disturbed by pymetrozine and exhibited similar patterns of sharp decline in activity in the phloem tissue and a significant increase the nonprobing. PMID- 22299349 TI - Residual control and lethal concentrations of GF-120 (spinosad) for Anastrepha spp. (Diptera: Tephritidae). AB - The objective of this study was to determine the relationship between residual time of GF-120 (spinosad) treatment and mortality in three species of Anastrepha Schiner. Concentrations of 96, 72, 48, and 24 ppm were aged on mango leaves under field conditions for 0, 3, 7, 10, 14, 17, and 21 d after application. We found that Anastrepha ludens, A. obliqua, and A. serpentina were highly sensitive to spinosad. The effects of spinosad were not reduced over the 4 d after the initial application, even at a concentration of 24 ppm. Mortality at 14 d after the application of 72 and 96 ppm of spinosad was similar in each of the three fruit fly species. In addition, we found that 24 ppm of spinosad was consumed the most by each species even though no direct relationship between the rate of consumption per female and the dose of the product was observed, in this test, higher consumption of active ingredient was observed at a concentration of 72 ppm, for A. ludens, 48 ppm for A. obliqua, and 96 ppm for A. serpentina. Our results suggest that a spinosad concentration of 72 ppm may effectively control these pests for at least 10 d under field conditions. PMID- 22299350 TI - Effects of transgenic Bt rice on growth, reproduction, and superoxide dismutase activity of Folsomia candida (Collembola: Isotomidae) in laboratory studies. AB - Transgenic rice expressing Bacillus thuringiensis (Bt) CrylAb protein is expected to be commercialized in China in the near future. The use of Bt rice for controlling insect pests sparks intensive debates regarding its biosafety. Folsomia candida is an euedaphic species and is often used as a "standard" test organism in assessing effects of environmental pollutants on soil organisms. In this study, growth, development, reproduction, and superoxide dismutase activity (SOD) of F. candida were investigated in the laboratory for populations reared on leaf tissue or leaf-soil mixtures of two CrylAb rice lines and a non-Bt rice isoline. Two independent tests were performed: 1) a 35-d test using petri dishes containing yeast diet (positive control) or fresh rice leaf tissue, and 2) a 28-d test in soil-litter microcosms containing yeast or a mixture of soil and rice leaf tissue. Biological parameters measured in both tests were number of progeny production, population growth rate, and SOD activity. For the petri dish test, data measured also included insect body length and number of exuviation. There were no significant differences between the populations reared on Bt and non-Bt rice leaf tissue in all measured parameters in both tests and for both Bt rice lines, suggesting no significant effects of the CrylAb protein in Bt rice on F. candida in the laboratory studies. Results of this study should add additional biosafety proofs for use of Bt rice to manage rice pests in China. PMID- 22299351 TI - Cost-effective binomial sequential sampling of western bean cutworm, Striacosta albicosta (Lepidoptera: Noctuidae), egg masses in corn. AB - Striacosta albicosta (Smith) (Lepidoptera: Noctuidae), is a native pest of dry beans (Phaseolus vulgaris L.) and corn (Zea mays L.). As a result of larval feeding damage on corn ears, S. albicosta has a narrow treatment window; thus, early detection of the pest in the field is essential, and egg mass sampling has become a popular monitoring tool. Three action thresholds for field and sweet corn currently are used by crop consultants, including 4% of plants infested with egg masses on sweet corn in the silking-tasseling stage, 8% of plants infested with egg masses on field corn with approximately 95% tasseled, and 20% of plants infested with egg masses on field corn during mid-milk-stage corn. The current monitoring recommendation is to sample 20 plants at each of five locations per field (100 plants total). In an effort to develop a more cost-effective sampling plan for S. albicosta egg masses, several alternative binomial sampling plans were developed using Wald's sequential probability ratio test, and validated using Resampling for Validation of Sampling Plans (RVSP) software. The benefit cost ratio also was calculated and used to determine the final selection of sampling plans. Based on final sampling plans selected for each action threshold, the average sample number required to reach a treat or no-treat decision ranged from 38 to 41 plants per field. This represents a significant savings in sampling cost over the current recommendation of 100 plants. PMID- 22299352 TI - Economic injury level for the coffee berry borer (Coleoptera: Curculionidae: Scolytinae) using attractive traps in Brazilian coffee fields. AB - The currently existing sample procedures available for decision-making regarding the control of the coffee berry borer Hypothenemus hampei (Ferrari) (Coleoptera: Curculionidae: Scolytinae) are time-consuming, expensive, and difficult to perform, compromising their adoption. In addition, the damage functions incorporated in such decision levels only consider the quantitative losses, while dismissing the qualitative losses. Traps containing ethanol, methanol, and benzaldehyde may allow cheap and easy decision-making. Our objective was to determine the economic injury level (EIL) for the adults of the coffee berry borer by using attractant-baited traps. We considered both qualitative and quantitative losses caused by the coffee borer in estimating the EILs. These EILs were determined for conventional and organic coffee under high and average plant yield. When the quantitative losses caused by H. hampei were considered alone, the EILs ranged from 7.9 to 23.7% of bored berries for high and average-yield conventional crops, respectively. For high and average-yield organic coffee the ELs varied from 24.4 to 47.6% of bored berries, respectively. When qualitative and quantitative losses caused by the pest were considered together, the EIL was 4.3% of bored berries for both conventional and organic coffee. The EILs for H. hampei associated to the coffee plants in the flowering, pinhead fruit, and ripening fruit stages were 426, 85, and 28 adults per attractive trap, respectively. PMID- 22299353 TI - Distribution and abundance of Adelges tsugae (Hemiptera: Adelgidae) within hemlock trees. AB - We studied the distribution of hemlock woolly adelgid, Adelges tsugae Annand (Hemiptera: Adelgidae), within hemlock trees for three summer (progrediens) and two winter (sistens) generations in northern Georgia. Eastern hemlock, Tsuga canadensis (L.) Carriere, trees were treated with 0, 10, or 25% of 1.5 g of imidacloprid per 2.5 cm of tree diameter at breast height and fertilized or not in a factorial design. Adelgid ovisacs per centimeter of branch were more abundant from June 2007 to June 2008 in the upper tree crown of insecticide untreated trees and when all trees were combined and that was the general trend for most comparisons. However, ovisacs were more abundant in the lower crown of insecticide treated trees in June 2008. More sistens nymphs settled on the upper crown branches than on the lower branches in summers 2007 and 2008. Higher eggs per ovisac were observed in the upper crown in February 2008 and in both the winter and summer 2009. In contrast, adelgids were more fecund in the lower crown in June 2008. On fertilized trees, eggs laid per adult were higher in the upper crown in February 2008. In summer 2008, eggs per ovisac were higher in the lower crown, but this reversed again to the upper crown by summer 2009. New growth of branches also varied among sample dates. These data demonstrate the variable distribution of adelgid and hemlock growth within trees over time and suggest that sampling only one crown area will not provide accurate estimates of adelgid densities. PMID- 22299354 TI - Evidence for limited spatial spread in an exotic longhorn beetle, Tetropium fuscum (Coleoptera: Cerambycidae). AB - The longhorn beetle Tetropium fuscum F. (Coleoptera: Cerambycidae) has become established in Nova Scotia, Canada, where it coexists with Tetropium cinnamopterum Kirby. The two Tetropium species share a similar ecological niche and use the same volatile cues for mate attraction. Exotic T. fuscum was introduced near Halifax, Nova Scotia, in approximately 1990, but the rate of its spread 20 yr later has not been documented. We report a large-scale, 3-yr study that investigates the distribution of T. fuscum relative to its site of introduction. Traps baited with male-produced pheromone and host volatiles were used to estimate the relative abundance of the two Tetropium species. Adult T. fuscum emerged 1-2 wk earlier than T. cinnamopterum each year between 2008 and 2010. The spatial distribution of T. fuscum was characterized by a sharp decline in abundance in relation to its point of introduction, up to a threshold distance of approximately 80 km beyond which T. fuscum is rare in comparison with native T. cinnamopterum. The restricted range of T. fuscum 20 yr after its introduction may be attributed to limited dispersal of adults or reproductive failures of low density populations. The distribution of T. fuscum seemed stable between 2008 and 2010. In 1 of 3 yr, the abundance of T. cinnamopterum increased with the distance to the site of introduction of T. fuscum, which suggests competitive interactions between the two Tetropium species. PMID- 22299355 TI - Relative performance of Lindgren multiple-funnel, Intercept panel, and Colossus pipe traps in catching Cerambycidae and associated species in the southeastern United States. AB - In 2004, we evaluated the relative performance of 8-unit Lindgren multiple-funnel (funnel), Intercept panel (panel), and Colossus pipe (pipe) traps, baited with ethanol and ac-pinene lures, in catching saproxylic beetles (Coleoptera) in pine stands in northern Florida and western South Carolina. Panel traps were as good as, if not better than, funnel and pipe traps for catching Cerambycidae. In particular, more Monochamus titillator (F.) were captured in panel traps than in pipe and funnel traps. Of three species of Buprestidae captured in our study, most Buprestis lineata F. were caught in panel traps, whereas most Acmaeodera tubulus (F.) were caught in funnel traps. Catches of Chalcophora virginiensis Drury and the root-feeding weevils Hylobius pales Herbst an dPachylobius picivorus LeConte (Curculionidae) were unaffected by trap type. Among bark beetles (Curculionidae: Scolytinae), catches of Ips grandicollis (Eichhoff) were unaffected by trap type, whereas most Dendroctonus terebrans (Olivier) were caught in panel traps, most Hylastes salebrosus Eichhoff were caught in panel and pipe traps, and most Hylastes tenuis Eichhoff were caught in funnel traps. Among ambrosia beetles (Curculionidae: Scolytinae), panel traps caught the most Xyleborinus saxesenii (Ratzeburg), whereas pipe traps caught the most Xyleborus Eichhoff spp. More Xylosandrus crassiusculus (Motschulsky) and Dryoxylon onoharaensis (Murayama) were caught in panel and funnel traps than in pipe traps. Among bark beetle predators, more Platysoma Leach spp. (Histeridae) were caught in pipe and panel traps than in funnel traps, whereas most Lasconotus Erichson spp. (Zopheridae) were caught in funnel traps. Variation among trap performance for various species suggests that managers should consider more than one type of trap in their detection programs. PMID- 22299356 TI - The effect of exposure to imidacloprid on Asian longhorned beetle (Coleoptera: Cerambycidae) survival and reproduction. AB - The effect of imidacloprid delivery method and application rate on survival of adult Asian longhorned beetles, Anoplophora glabripennis (Motschulsky), was studied, along with the effect of repeated daily ingestion of imidacloprid on the survival and reproductive capacity of adult females. Beetles exposed repeatedly to 50 ppm imidacloprid died in < 2-3 wk, whether dosed orally each day, or through contact exposure. Beetles given 1 microl of 50 ppm imidacloprid daily for two, three, four, or five consecutive days died sooner with increasing consecutive days: the beetles treated for 5 d all died within 15 d, while 80% of beetles treated for only 2 d lived > 8 wk. For females given 1 microl daily, across a range of doses from 2 to 50 ppm imidacloprid, the total number of viable eggs laid was reduced with increasing dosage, but percentage egg viability was not affected. Survival of females at dosages of 10 or 30 ppm/d was not significantly reduced compared with controls but these females laid 23-38% fewer viable eggs, suggesting a sublethal effect of imidacloprid. Female beetles given 1 microl/d of 40 or 50 ppm imidacloprid died more quickly than controls and viable egg production was reduced 82-93%, because of a combination of lethal and sublethal effects of intoxication. PMID- 22299357 TI - Life stage toxicity and residual activity of insecticides to codling moth and oriental fruit moth (Lepidoptera: Tortricidae). AB - The codling moth, Cydia pomonella (L.), and oriental fruit moth, Grapholita molesta (Busck), are two key pests of apple (Malus domestica Borkh.) in North Carolina. Growers extensively relied on organophosphate insecticides, primarily azinphosmethyl, for > 40 yr to manage these pests. Because of organophosphate resistance development and regulatory actions, growers are transitioning to management programs that use new, reduced-risk, and OP-replacement insecticides. This study evaluated the toxicity of a diversity of replacement insecticides to eggs, larvae, and adults, as well as an assessment of their residual activity, to codling moth and oriental fruit moth. Laboratory-susceptible strains of both species were used for all bioassays. Fresh field-harvested apples were used as a media for assessing the ovicidal activity of insecticides. For larval studies, insecticides were topically applied to the surface of lima bean-based diet, onto which neonates were placed. Toxicity was based on two measures of mortality; 5-d mortality and development to adult stage. Ovicidal bioassays showed that oriental fruit moth eggs were generally more tolerant than codling moth eggs to insecticides, with novaluron, acetamiprid, and azinphoshmethyl having the highest levels of toxicity to eggs of both species. In contrast, codling moth larvae generally were more tolerant than oriental fruit moth to most insecticides. Methoxyfenozide and pyriproxyfen were the only insecticides with lower LC50 values against codling moth than oriental fruit moth neonates. Moreover, a number of insecticides, particularly the IGRs methoxyfenozide and novaluron, the anthranilic diamide chlorantriliprole, and the spinosyn spinetoram, provided equal or longer residual activity against codling moth compared with azinphosmethyl in field studies. Results are discussed in relation to their use in devising field use patterns of insecticides and for insecticide resistance monitoring programs. PMID- 22299358 TI - Reducing insecticide volume and nontarget effects of ambrosia beetle management in nurseries. AB - Ambrosia beetles (Coleoptera: Curculionidae: Scolytinae) are increasingly important pests of nursery-grown trees because of the arrival of several invasive species. Ambrosia beetles bore into young trees and inoculate them with ambrosia fungus, which interferes with vascular transport resulting in limb or tree death. In spring, when beetles are active, growers make frequent applications of pyrethroid insecticides to susceptible tree species to deter beetles from boring into trees. Applications often are made with airblast sprayers that forcefully release insecticide mist that billows through nursery beds. Our objective was to compare the environmental, nontarget, and economic effects of airblast sprayer applications to applications made with a new dual-nozzle spray wand that makes targeted applications only to tree trunks where beetles attack. Through replicated experiments at commercial nurseries, we found that 5 times more insecticide was released by airblast sprayers than the manual spray wand. The extra insecticide from airblast applications landed on tree canopies, between rows, and left the nursery beds as drift. As a consequence of not spraying tree canopies, 50% more natural enemies and 50% fewer spider mites were captured in nursery beds treated with the manual spray wand than beds treated with the airblast sprayer. Manual applications require 12 times more labor than airblast applications. However, increased need for expensive miticide applications may make manual applications an economically feasible strategy for integrated pest management (IPM) of ambrosia beetles in nurseries. PMID- 22299359 TI - Prerelease exposure to methyl eugenol increases the mating competitiveness of sterile males of the oriental fruit fly (Diptera: Tephritidae) in a Hawaiian orchard. AB - Males of the oriental fruit fly, Bactrocera dorsalis (Hendel), are strongly attracted to methyl eugenol (ME), and recent work demonstrated that ingestion of this chemical enhances male mating success, apparently owing its role as a precursor in the synthesis of the male sex pheromone. The current study expanded upon earlier laboratory and field-cage experiments by assessing whether prerelease exposure to ME increased the mating competitiveness of mass-reared, sterile males in Hawaiian orchards. Releases of sterile males from a pupal color based sexing strain were made weekly in two fruit orchards over 8 mo, with the sterile males at one site given ME for 24 h before release (treated) and the sterile males at the other site given no ME before release (control). Fruits were collected periodically during the study period, and eggs were dissected and incubated to score hatch rate. At both sites, releases of sterile males increased the proportion of unhatched eggs well above prerelease levels, but the incidence of egg sterility was consistently, and statistically, greater in the orchard receiving ME-exposed males. Computed over the entire release period, the average value of Fried's competitive index (that characterizes the mating success of sterile males relative to their wild counterparts) for ME-treated males was 3.5 times greater than that for control males, although this difference was not statistically significant. However, when computed over the period during which egg sterility values were elevated and stable, presumably when females inseminated before the releases were rare or absent, the competitive indices were significantly higher for ME-treated sterile males. The implications of these results for implementing the Sterile Insect Technique against this species are discussed. PMID- 22299360 TI - Botanical insecticides in controlling Kelly's citrus thrips (Thysanoptera: Thripidae) on organic grapefruits. AB - Kelly's citrus thrips, Pezothrips kellyanus (Bagnall) (Thysanoptera: Thripidae) was first recorded in Cyprus in 1996 and became an economic citrus pest. In Cyprus, Kelly's citrus thrips larvae cause feeding damage mainly on immature lemon and grapefruit fruits. Use of botanical insecticides is considered an alternative tool compared with synthetic chemicals, in offering solutions for healthy and sustainable citrus production. During 2008-2010, the efficacy of the botanical insecticides azadirachtin (Neemex 0.3%W/W and Oikos 10 EC), garlic extract (Alsa), and pyrethrins (Vioryl 5%SC) was evaluated in field trials against Kelly's citrus thrips larval stage I and II aiming at controlling the pest's population and damage to organic grapefruit fruits. In each of the trial years treatments with pyrethrins and azadirachtin (Neemex 0.3%W/W) were the most effective against Kelly's citrus thrips compared with the untreated control (for 2008: P < 0.018; for 2009: P < 0.000; for 2010: P < 0.008). In 2008, the mean number of damaged fruits in treatments with pyrethrins and Neemex was 9.6 (19.2%) and 9.7 (19.5%) respectively, compared with 12.2 (24.3%) in the untreated control. In 2009, the mean number of damaged fruits in treatment with pyrethrins was 3.7 (7.3%) and 3.9 (7.8%) in treatment with Neemex compared with 8.6 (17.3%) in the untreated control, while in 2010 the mean damaged fruits in these treatments was recorded at 18.7 (37.5%) and 19.6 (39.2), respectively, compared with 29.6 fruits (59.2%) in the control. Oikos 10 EC showed significant effect only in 2009 and 2010. In these years, the mean number of damaged fruits was recorded at 5.5 and 21.2 compared with 8.6 and 29.6 fruits in the untreated control, respectively. Garlic extract showed the lowest effect from all the botanicals used compared with the untreated control. PMID- 22299361 TI - A novel biorational pesticide: efficacy of methionine against Heraclides (Papilio) cresphontes, a surrogate of the invasive Princeps (Papilio) demoleus (Lepidoptera: Papilionidae). AB - ABSTRACT The Southeast Asian citrus-feeding butterfly Princeps (Papilio) demoleus (L.) was recently introduced into the Americas, causing an imminent threat to citrus production and ornamental flora. The human nutrient amino acid methionine has been shown by us to disrupt aminoacid-modulated ion transport systems in caterpillars and other insect larvae that possess an alkaline midgut. Heraclides (Papilio) cresphontes was bioassayed as a United States Department of Agriculture permitted surrogate of the Florida quarantined P. demoleus to test the potential efficacy of methionine. Larvae were allowed to feed ad libitum on wild lime plants with leaves treated with methionine or proline. Methionine caused 100% mortality in first through fourth instars in a time- and dose-dependent manner, as determined by probit analysis whereas proline was not toxic. Wild lime host plants did not exhibit phytotoxicity with methionine treatments during a 14 d test period. It is concluded that methionine is an effective larvicide against H. cresphontes, and therefore may be a candidate environmentally safe biorational pesticide for use against invasive P. demoleus in the Americas. PMID- 22299362 TI - Effect of rootstock on mango fruit susceptibility to infestation by Anastrepha obliqua. AB - The effect of the use of rootstock Criollo on the susceptibility of Manila mango fruit to infestation by Anastrepha obliqua (Macquart) was determined in the present investigation. Growth, quality parameters (Soluble solids content (%), citric acid content (%), firmness, monoterpene volatiles (3-carene, limonene, alpha-pinene, and beta-myrcene), main flavonoids content (milligrams/100 g fresh pulp), and larvicidal activity of methanolic extracts, as well as the degree of infestation during preharvest development of the fruits were analyzed. The results indicated that the rootstock did not have any significant effect on growth, soluble solids content, or citric acid content; although it increased firmness as well as 3-carene levels and main flavonoids content, resulting in a greater resistance to infestation by A. obliqua. The obtained results support the use of this rootstock because of the beneficial effects observed on the resistance of mango fruit to infestation by this fruit fly. PMID- 22299363 TI - Radiation biology and inherited sterility of light brown apple moth (Lepidoptera: Tortricidae): developing a sterile insect release program. AB - The radiation biology of two geographically isolated populations of the light brown apple moth [Epiphyas postvittana (Walker)] was studied in Australia and New Zealand as an initiation of a SIT/F1 sterility program. Pharate and < or = 2 d pre-emergence pupae were exposed to increasing radiation doses up to a maximum dose of 300 Gy. Fertility and other life history parameters were measured in emerging adults (parental) and their progeny (F1-F3 adults). Parental fecundity was significantly affected by increasing irradiation dose in pharate pupae only. For both populations, parental egg fertility declined with increasing radiation. This was most pronounced for the irradiated parental females whose fertility declined at a higher rate than of irradiated males. At 250 Gy, females < or = 2 d preemergence pupae produced few larvae and no adults at F1. No larvae hatched from 250 Gy-irradiated female pharate pupae. At 300 Gy, males still had residual fertility of 2-5.5%, with pharate pupae being the more radio-sensitive. Radiation induced deleterious inherited effects in offspring from irradiated males were expressed as increased developmental time in F1 larvae, a reduction in percent F1 female survival, decreased adult emergence and increased cumulative mortality over subsequent generations. Males irradiated at > or = 150 Gy produced few but highly sterile offspring at F1 and mortality was > 99% by F2 egg. PMID- 22299365 TI - Optimizing ethanol-baited traps for monitoring damaging ambrosia beetles (Coleoptera: Curculionidae, Scolytinae) in ornamental nurseries. AB - The exotic ambrosia beetles Xylosandrus crassiusculus (Motschulsky) and Xylosandrus germanus (Blandford) (Coleoptera: Curculionidae: Scolytinae) are serious pests in ornamental tree nurseries. To optimize bottle-traps as a monitoring system for X. crassiusculus and X. germanus in nurseries, we tested whether increasing the rate of commercial ethanol lures improved captures or early detection of these species. Experiments were conducted in Ohio (2008 and 2009) and Virginia (2008), two states that have experienced significant damage from X. crassiusculus, X. germanus, or both. There were four treatments: no-lure (unbaited control), 1-ethanol lure, 2-ethanol lures and 1 + 1-ethanol lures (one lure in the trap and one suspended 0.5 m above the trap). Captures of X. crassiusculus and X. germanus were higher in all ethanol treatments than unbaited controls, and were generally higher in treatments with two lures versus one. There was no difference in beetle captures between the 2-lure and 1 + 1-lure treatments. First detection of X. crassiusculus and X. germanus occurred more consistently in the treatments with two lures than one lure. Xyleborinus saxesenii (Ratzeburg), Anisandrus sayi Hopkins, Hypothenemus dissimilis Zimmermann, and Hypothenemus eruditus Westwood were also more attracted to traps baited with ethanol than unbaited controls. X. saxesenii was captured in higher numbers in the treatments with two lures than one in Virginia but not in Ohio. There was no difference in captures of the other species among ethanol treatments. The current research shows that ethanol release rates influence sensitivity of traps for detecting emergence of overwintered ambrosia beetles. PMID- 22299364 TI - Lack of interactions between fire ant control products and white grubs (Coleoptera: Scarabaeidae) in turfgrass. AB - Insecticides are widely used to manage turfgrass pest such as white grubs (Coleoptera: Scarabaeidae). Red imported fire ants, Solenopsis invicta (Buren) are important predators and pests in managed turfgrass. We tested the susceptibility of white grub life stages (adults, egg, and larvae) to predation by S. invicta and determined if insecticides applied for control of S. invicta would result in locally greater white grub populations. Field trials over 2 yr evaluated bifenthrin, fipronil, and hydramethylnon applied to large and small scale turfgrass plots for impacts on fire ant foraging and white grub populations. Coincident with these trials, adults, larvae, and eggs of common scarab species were evaluated for susceptibility to predation by S. invicta under field conditions. Field trials with insecticides failed to show a significant increase in white grub populations resulting from treatment of turfgrass for fire ants. This, in part, may be because of a lack of predation of S. invicta on adult and larval scarabs. Egg predation was greatest at 70% but < 20% of adults and larvae were attacked in a 24 h test. Contrary to other studies, results presented here suggest that fire ants and fire ant control products applied to turfgrass have a minimal impact on white grub populations. PMID- 22299366 TI - Effect of soil type and exposure duration on mortality and transfer of chlorantraniliprole and fipronil on Formosan subterranean termites (Isoptera: Rhinotermitidae). AB - The uptake and potential transfer of chlorantraniliprole and fipronil by the Formosan subterranean termite, Coptotermes formosanus Shiraki, was investigated in the laboratory by using donor-recipient model bioassays. Two different types of substrates, sandy loam soil (18.6% organic matter) and sand (0.19% organic matter), were used to evaluate how these treated substrates impact the direct mortality and transfer efficiency of the two nonrepellent termiticides tested at different concentrations. Chlorantraniliprole exhibited a more delayed mortality on termites than fipronil in sand. In soil, chlorantraniliprole did not cause higher mortality to either donor or recipient termite at any of the tested concentrations during a 21-d test period when compared with controls. Compared with the controls, a greater number of donors died in the soil treated with fipronil at 14 h postinteraction, and higher death of recipients occurred at 21 d but only in the 60-ppm concentration tested. Our data showed that chlorantraniliprole performed best in substrate with low organic matter against PMID- 22299367 TI - Evaluation of Aprostocetus hagenowii (Hymenoptera: Eulophidae) for the control of American cockroaches (Dictyoptera: Blattidae) in sewers and crevices around buildings. AB - The objective of this study was to evaluate the potential of Aprostocetus hagenowii (Ratzeburg) (Hymenoptera: Eulophidae) to control American cockroaches, Periplaneta americana (L.) (Dictyoptera: Blattidae), in sewer manholes and in crevices around buildings. Parasitoids were released weekly for 12 wk from laboratory parasitized heat-killed oothecae, and parasitism monitored using sentinel oothecae of American cockroaches. In addition, preference of A. hagenowii for 1- to 4-wk-old oothecae was evaluated in the laboratory. A. hagenowii females showed no preference for any ootheca age. Twenty of the 30 tested females parasitized one ootheca, whereas the other 10 parasitized two oothecae. The total progeny (males, females, and total) that emerged from a single ootheca parasitized by a female was not significantly different to the total progeny that emerged from two oothecae parasitized by a female. The number of males, females, and total progeny that emerged from the second parasitized ootheca was significantly less than the number that emerged from the first parasitized ootheca. The weekly mean sentinel oothecal parasitism rate in wall crevices was 18.1 +/- 3.2% and in sewer manholes was 13.3 +/- 2.0%. The mean number of released A. hagenowii females per number of parasitized sentinel oothecae recorded in crevices was 189 +/- 18, whereas it was 428 +/- 50 in sewers. A. hagenowii females were more effective at parasitizing sentinel oothecae placed at high and middle levels in manholes than at a low level when releases were made at the midpoint of the manhole shaft. PMID- 22299368 TI - Fitness costs of an insecticide resistance and their population dynamical consequences in the oriental fruit fly. AB - Naled is a commonly used insecticide for controlling populations of the oriental fruit fly, Bactrocera dorsalis (Hendel), in Taiwan and other countries. B. dorsalis has developed resistance to the insecticide, and the resistance management is an important issue. Ecological effects (e.g., fitness costs) of the resistance, when fully understood, can be used for the resistance management. This study examined the effects of the insecticide resistance on important life history traits (i.e., survival rates, stage durations, and fecundity) of the oriental fruit fly by comparing the traits of insecticide resistant individuals and susceptible individuals. Population dynamical properties were also examined using a stage-structured matrix model that was parameterized with the empirical data. The results revealed that susceptible individuals had shorter stage durations (e.g., grew faster) and reproduced more than resistant individuals. The average longevity of sexually mature susceptible adults was longer than that of sexually mature resistant adults. The matrix population model predicted that a population of the susceptible individuals would grow faster than a population of the resistant individuals in the absence of the insecticide. The sensitivity analysis of the model suggests that the sexually immature adult stage is a good candidate for controlling B. dorsalis populations. PMID- 22299369 TI - Molecular characterization of the sigma class gutathione S-transferase from Chilo suppressalis and expression analysis upon bacterial and insecticidal challenge. AB - The insect glutathione S-transferases (GSTs) play an important role in the detoxification of xenobiotic compounds and are related to insecticides resistance. The full-length cDNA sequences encoding the sigma class GST protein (CsGSTsigma) was cloned from the Asiatic rice borer, Chilo suppressalis (Walker), one of the most important rice pests in Asia. The comparison of amino acid sequences showed that CsGSTsigma is highly similar to the sigma GST isolated from the domestic silkworm, Bombyx mori (L.). A homology model of CsGSTsigma was constructed and its binding environment for GSH is identical to that in the equivalent site of sigma GST from the fruit fly, Drosophila melanogaster Meigen. The developmental changes of the relative mRNA expression levels of CsGSTsigma were examined in Asiatic rice borer, and the highest expression level of this gene is in adult followed by the third-instar larvae stage. Furthermore, one gram positive bacterium and two chemical insecticides were found to be able to induce the increasing expression of CsGSTsigma, suggesting that CsGSTsigma might work as an antioxidant enzyme to against the negative effects caused by both pathogens and xenobiotics. PMID- 22299370 TI - Effect of MIR604 transgenic maize at different stages of development on western corn rootworm (Coleoptera: Chrysomelidae) in a central Missouri field environment. AB - The establishment and survival of western corn rootworm, Diabrotica virgifera virgifera LeConte, was evaluated on transgenic Bacillus thuringiensis Berliner maize, Zea mays L., expressing the mCry3A protein (MIR604) and non-Bt maize with the same genetic background (isoline maize) at different stages of development in 2007 and 2008. Overall, western corn rootworm larval recovery, root damage, and adult emergence were significantly higher on isoline maize compared with MIR604. The number of larvae and adults collected from MIR604 did not significantly differ among egg hatch dates from each maize developmental stage evaluated in either year. In 2007, damage to isoline maize roots was lower than expected and never exceeded 0.24 nodes of damage. In 2008, over 0.60 nodes of damage occurred on isoline maize roots. The mean weight and head capsule width of larvae and adults recovered from MIR604 and isoline maize were generally not significantly different. Results are discussed in relation to insect resistance management of western corn rootworm. PMID- 22299371 TI - Experimental use of two standard tick collection methods to evaluate the relative effectiveness of several plant-derived and synthetic repellents against Ixodes scapularis and Amblyomma americanum (Acari: Ixodidae). AB - We used two standard tick collection methods to test the relative effectiveness of two natural product compounds (nootkatone and carvacrol, classified as an eremophilene sesquiterpene and a monoterpene, respectively, that are derived from botanical sources) with commercially-available plant-derived (EcoSMART Organic Insect Repellent, comprised of plant essential oils) and permethrin-based (Repel Permanone) repellents against Ixodes scapularis Say and Amblyomma americanum (L.). Cloth drags were equally effective in sampling both species of host-seeking nymphs, whereas CO, traps attracted primarily A. americanum. All four repellents performed well on drags, with nootkatone and Permanone Repel (100% repelled through 14 d) slightly more effective than carvacrol and EcoSMART (90.7% and 97.7% repelled at 14 d, respectively) at repelling I. scapularis nymphs. Although the same trend in percent repellency was noted in the CO2 trap trial against both A. americanum nymphs and adults, EcoSMART outperformed Permanone in repelling A. Americanum nymphs after 14 d in the drag trial. Generally, the effectiveness of all repellents tested declined over time. The use of tick drags and CO2 traps was rapid, inexpensive, and easy to use in determining the relative effectiveness of repellents in the field. PMID- 22299372 TI - Electrical penetration graph analysis of the feeding behavior of soybean aphids on soybean cultivars with antibiosis. AB - The soybean aphid, Aphis glycine Matsumura (Hemiptera: Aphididae), is a major pest of soybean. In the current study, we used the Electrical Penetration Graph technique to study feeding behavior of soybean aphids on antibiotic-resistant soybean lines KS1621, KS1613, and KS1642, and a susceptible soybean line, KS4202. We observed that soybean aphids spent significantly shorter periods of time in the sieve element phase but slightly more times in nonprobing phases in all three resistant lines than in the susceptible control. Our study suggests that resistance factors exist in the phloem of the resistant soybean lines, and that these lines may contain antixenosis in addition to antibiosis. PMID- 22299373 TI - Evaluation of buffalograss genotypes and full-sibs for chinch bug resistance. AB - Fifteen buffalograss, Buchloe dactyloides (Nutt.) Engelm, genotypes and 94 diploid full-sib progeny were evaluated for western chinch bug, Blissus occiduus Barber (Hemiptera: Lygaeidae), resistance in two separate studies. The experimental design for each study was a completely randomized design. Adult chinch bugs were introduced onto caged single clone genotypes and progeny in the greenhouse. Chinch bug damage was assessed using a 1-5 visual damage rating scale with 1 = < or = 10%; 2 = 11-30%; 3 = 31-50%; 4 = 51-70%; and 5 = > or = 70% of the buffalograss leaf area with severe discoloration, or dead tissue. Highly significant differences were found among the genotypes and progeny for chinch bug damage. Among the genotypes, Legacy, Prestige, 184, 196, Bowie, NE 3297, NE 2769, and NE 2768 were moderately resistant with damage ratings of > 1, but < 3, while NE 2990, NE 2838, and 1-57-19 were moderately susceptible with damage ratings of > or = 3, but < 4. Among the progeny, one progeny (MP45) was highly resistant with a chinch bug damage rating of 1.0, 78 progeny (83%) had moderate resistance, with damage ratings of > 1.0 and < 3.0, 13 progeny (14%) were moderately susceptible with damage ratings ranging from 3.0 to 3.9, while only two were highly susceptible with damage ratings of > or = 4.0. The significant variability among genotypes and progeny for chinch bug resistance indicates the ability to improve buffalograss resistance to chinch bugs through selection or hybridization of selected genotypes. PMID- 22299374 TI - Influence of age, mating status, sex, quantity of food, and long-term food deprivation on red flour beetle (Coleoptera: Tenebrionidae) flight initiation. AB - Effects of age, sex, presence or absence of food, mating status, quantity of food, and food deprivation on rate of and time of flight initiation of the red flour beetle, Tribolium castaneum (Herbst), were determined. Flight initiation declined with increasing age in both presence and absence of food. However, flight initiation was lower when food was present in the flight chambers than in the absence of food. In the presence of food, both mated and virgin beetles were equally likely to disperse by flight. However, in the absence of food, mated beetles initiated flight more readily that virgin individuals. Flight initiation was greatest when little or no food was present. The presence of varying quantities of food inside the flight chambers impacted the number of progeny produced by females before flight, but not the timing of flight. Rate of flight initiation was higher for beetles deprived of food for short periods of time compared with flight initiation of beetles with food in the flight chamber. Flight initiation decreased with increasing time without food. There were no differences in flight tendencies between males and females in the experiments reported here. Our results suggest that T. castaneum uses flight as a mechanism to disperse to new environments during almost any part of their life span and that this type of dispersion does not fit with the model of the so-called true migratory species that involves an "oogenesis-flight syndrome. PMID- 22299375 TI - Relationship between population growth of the red flour beetle Tribolium castaneum and protein and carbohydrate content in flour and starch. AB - The effects of eight diets (atta flour, wheat flour, self-rising flour, rice flour, custard powder, corn flour, tapioca starch, and potato starch) on the development of the red flour beetle, Tribolium castaneum (Herbst), reared at 29 31 degrees C and 66-70% RH were assessed. Five pairs of male and female T. castaneum were reared on the respective diets for 28 d before the experimental setup was dismantled and adult counts were recorded. In another experiment, the insects were allowed to mate and oviposit in each flour or starch type over a period of 7 d before being removed. The counting of pupae and adult emergence began on the day of emergence and was continued on a daily basis until day 140. Proximate analysis was performed for chemical composition of each diet, and the numbers of new adults that developed were found to be positively correlated (r2 = 0.97; P < 0.05) with the protein content and negatively correlated (r2 = 0.93; P < 0.05) with the carbohydrate content. For T. castaneum, the suitable diets were ranked as follows: atta flour > wheat flour > self-rising flour > rice flour > custard powder > corn flour > tapioca starch > potato starch. T. castaneum larval development to the pupal and adult stages developed significantly faster in atta flour (P < 0.05) than in the other diets, and the greatest number of progeny was produced from beetles reared on atta flour. Fewer adults emerged from wheat flour, self-rising flour, and rice flour, and no new emergences were recorded for the remaining diets. Developmental rate was much slower in beetles reared on diets in which a low number in progeny was produced. These data illustrate that different diets can influence the sustainability of these insects and affect their development and growth. PMID- 22299376 TI - Potential of Tenebrio molitor (Coleoptera: Tenebrionidae) as a bioassay probe for Metarhizium brunneum (Hypocreales: Clavicipitaceae) activity against Ixodes scapularis (Acari: Ixodidae). AB - The yellow mealworm, Tenebrio molitor L., has been used to indicate qualitatively the presence of entomopathogenic fungi in the soil or as a model for evaluating stress and other factors on fungal activity. Although this beetle appears highly susceptible to many of these fungi, little quantitative information is available on the sensitivity of T. molitor to a specific fungus and, therefore, fungal presence or as an indicator for pathogenicity to other species. The purpose of this study was to establish the suitability of T. molitor larvae as a bioassay probe for Metarhizium brunneum for comparison against the blacklegged tick, Ixodes scapularis. Nine concentrations of M. brunneum strain F52 ranging from 1.0 x 10(1) to 8.4 x 10(8) conidial/ml were simultaneously tested against T. molitor larvae and I. scapularis adults. Larvae of yellow mealworm were less sensitive to M. brunneum than I. scapularis adults (LC50's 4.4 x 10(7) and 1.7 x 10(5) conidia/ml, respectively, 4-wk post-treatment). The greater sensitivity of I. scapularis to the fungus suggests that the detection of fungal mycosis in mealworms would indicate sufficient inoculum to be pathogenic to I. scapularis and make this insect a suitable probe for evaluation of the presence and activity of M. brunneum against the blacklegged tick in field applications. PMID- 22299377 TI - QTc prolongation as a surrogate for drug-induced arrhythmias: fact or fallacy? AB - QTc prolongation is commonly used as a surrogate for drug-induced torsade de pointes (TdP) because it is frequently associated with TdP. However, TdP can also occur in the absence of QTc prolongation or even when QTc is shortened. In the absence of disturbances of lambda-TRIaD (lambda: cardiac wavelength, Triangulation, Reverse use dependence, Instability and Dispersion; TRIaD) QTc prolongation can be antiarrhythmic. In the presence of disturbances of lambda TRIaD, QTc prolongation still reduces proarrhythmia but frequently cannot overcome the proarrhythmic effect induced by lambda-TRIaD disturbances. Safety evaluation focused upon QTc prolongation (antiarrhythmic parameter) instead of disturbances of lambda-TRIaD (proarrhythmic parameters), is scientifically incorrect. Such evaluation can impede the development of highly valuable drugs, while not recognizing agents that disturb lambda-TRIaD and hereby endanger patient safety. It must be concluded that the century old proposal by Lewis that prolongation of action potential duration and refractory period can be antiarrhythmic is still correct, provided it is not contaminated by disturbances of lambda-TRIaD. PMID- 22299378 TI - Cardiogenic shock complicating acute myocardial infarction--a review. AB - Cardiogenic shock is characterized by inadequate tissue perfusion due to cardiac dysfunction and is the leading cause of death in patients hospitalized with acute myocardial infarction. Mortality from cardiogenic shock still remains high. The development of cardiogenic shock is rarely unexpected; most patients who develop cardiogenic shock do so within 48 hrs of admission, with only 10% shocked on arrival. Mortality rate is exceedingly high and reaches 70-80% in those treated conservatively. Early revascularization is the cornerstone treatment of acute myocardial infarction complicated by cardiogenic shock. According to the guidelines, revascularization is effective up to 36 hours after the onset of cardiogenic shock and performed within 18 hours after the diagnosis of cardiogenic shock. Primary percutaneous coronary intervention is the most efficient therapy to restore coronary flow in the infarct-related artery. However, invasive strategy in a developing country like ours is not only costly but also technically demanding. We present a case of acute myocardial infarction complicated with cardiogenic shock that underwent primary percutaneous coronary intervention and also review the incidence, pathophysiology, management and outcome of cardiogenic shock complicating acute myocardial infarction. PMID- 22299379 TI - Short-term blood pressure variability in relation to outcome in the International Database of Ambulatory blood pressure in relation to Cardiovascular Outcome (IDACO). AB - Ambulatory blood pressure monitoring not only provides information on the blood pressure level, but on the diurnal changes in blood pressure as well. The present review summarizes the main findings of the International Database on Ambulatory blood pressure in relation to Cardiovascular Outcome (IDACO) with regard to risk stratification based on short-term blood pressure variability. An exaggerated morning surge, exceeding the 90th percentile of the population, is an independent risk factor for mortality and cardiovascular and cardiac events. Conversely, a sleep-through or pre-awakening morning surge less than 20 mm Hg in systolic blood pressure is probably not associated with an increased risk of death or cardiovascular events. Blood pressure variability represented by the average of the daytime and nighttime SD weighted for the duration of the daytime and nighttime interval (SDdn) and by average real variability (ARV24) predicted outcome, but only improved the prediction of the composite cardiovascular events by 0.1%. Overall, results of analyses using the IDACO support the concept that short-term blood pressure variability adds to risk stratification, but 24-hour ambulatory blood pressure level is the most valuable predictor for use in clinical practice. PMID- 22299380 TI - Ten years single-centre experience with intra-aortic balloon pump. AB - OBJECTIVES: The objective of this study was to investigate the patient characteristics and outcomes in 1406 patients undergoing intra-aortic balloon pump (IABP) counterpulsation. METHODS: Between 1998 and 2008, 1406 consecutive patients were recorded in a prospective database. Based on the main clinical indication for IABP use, we defined 3 groups: group A, 630 cases of coronary ischaemia or infarction without serious left ventricular (LV) dysfunction; group B, 466 patients with left ventricular failure or cardiogenic shock; group C, 310 patients where IABP was used for miscellaneous procedures such as weaning from cardiopulmonary bypass or during high-risk angioplasty or surgery. RESULTS: Global mortality was 28% (n = 390), with a significant difference between group A (15%, n = 95) and group B (41%, n = 191) (P < 0.001). Mortality in group C was 34% (n = 104). Most insertions were done in the catheterization laboratory (n = 943) with subsequent mortality of 23% whereas 199 balloons were inserted in the operation room with 34% mortality. 170 balloons inserted in the intensive care unit resulted in 46% mortality (P < 0.001). Major IABP-induced complications were 6.8% with no statistical differences between the three groups. Advanced age, left ventricular failure and low BMI were identified as prognostic risk factors for early mortality. CONCLUSIONS: IABP deployed at an early clinical stage yields the best results, especially for acute coronary patients with preserved LV function whereas LV failure and late insertion result in worse outcome. PMID- 22299381 TI - Screening for silent myocardial ischaemia in patients with type 2 diabetes mellitus: a quest to improve selection of the target screening population. AB - OBJECTIVE: Despite the association of diabetes mellitus type 2 (DM2) with silent myocardial ischaemia (SMI) and a high prevalence of death due to coronary artery disease (CAD), screening for CAD in patients with DM2 remains controversial because of a lack of proof that it improves cardiac outcome. The aim of this study was to improve the diagnostic yield of the exercise stress test (EST) by introducing recently published life expectancy tables in selecting DM2 patients for coronary screening. METHODS: 359 patients with DM2 without history or symptoms of CAD were included to perform an EST after a clinical history and brief physical examination. Cardiovascular risk factor profiling was completed with blood and urine analysis. A lower heart rate was defined as bradycardia (heart rate less than 60 bpm), a higher blood pressure as a systolic blood pressure at rest of 130 mmHg of more. RESULTS: The prevalence of SMI was 14.5% (n = 52). The average number of additional cardiovascular risk factors per subject was 4. Multivariate logistic regression yields 4 significant predictors: (i) heart rate at rest (P= 0.015), (ii) a family history of cardiovascular disease (P = 0.017), (iii) systolic blood pressure at rest (P = 0.019), and, (iv) an LDL-c of 80 mg/dL or more (P = 0.021). CONCLUSION: Known risk factors for myocardial ischaemia were identified as significantly influencing the prevalence of SMI. No improvement in diagnostic yield could be identified by selecting the screening population using predicted life expectancy tables. PMID- 22299382 TI - Impact of fatty acid food reformulations on intake of Dutch young adults. AB - BACKGROUND: The Dutch'Task Force for the Improvement of the Fatty Acid Composition' initiated fatty acid reformulations in branches using vegetable oils and fats to reduce the trans (TFA) and saturated fatty acid (SFA) content of foods. OBJECTIVE: This study estimates the impact of recent reformulations in the task force food groups by estimating changes in median intake of TFA and SFA in Dutch young adults. METHODS: This is a modelling study with food consumption data of young adults. Intakes were estimated before reformulation using food composition data of 2001 as a reference and while including most recent fatty acid composition of foods for task force food groups. Food composition of other foods and food consumption was assumed unchanged. RESULTS: Average TFA intake significantly decreased from 1.0 E% in the reference to 0.8 E% in the reformulation scenario. Pastry, cakes and biscuits, and snacks contributed most to the decrease of TFA. Estimated SFA intake did not change. When solid baking and spreading fats were additionally replaced with fluid ones, SFA intake decreases from 12.9 E% to 12.1 E%. CONCLUSION: Fatty acid reformulation in the task force food groups contributed to reductions in TFA intake. For further reductions in SFA intake a different food choice is primordial. PMID- 22299383 TI - Advantages and limitations of antihypertensive treatment for stroke risk in a general population: the Akita Stroke Registry. AB - BACKGROUND: Although the association between stroke risk and blood pressure (BP) levels related to antihypertensive medication has been an object of study for a long time, there is little agreement as to the relationship in a general population study. METHODS AND RESULTS: We obtained mass health screening data regarding 156,847 (142,989 untreated and 13,858 treated) subjects from the Akita Prefectural Federation of Agricultural Cooperative for Health and Welfare from 1991 to 1998. Stroke events were determined from the Akita stroke registry between 1991 and 2001. A Poisson regression model, adjusting for possible confounding factors, was used to investigate the risk of first stroke among six BP-based categories (BP defined according to JNC-6), with or without antihypertensive medication. Stroke developed in 1,323 (0.8%) individuals in the study population within 3 years after the health examination. Among untreated groups, the relative hazard linearly increased with elevation of the BP grade. In the untreated group, stroke risk was significantly higher (relative hazard 2.1, 95% confidence interval (CI) 1.6-2.7) in the subjects with high-normal BP levels than with optimal BP levels. In the treated group, stroke risk was significantly higher in patients with high-normal BP levels (relative hazard 2.0, 95% CI 1.0 4.2) than with optimal BP levels. Furthermore, stroke risk was significantly higher in the treated groups with normal BP levels (relative hazard 3.1, 95% CI 2.0-4.9) compared with the untreated group with optimal BP levels. CONCLUSIONS: Although antihypertensive medication can reduce stroke risk, treated patients within non-hypertension levels may still have a higher risk compared with untreated subjects of the same categories. PMID- 22299384 TI - Quantitative assessment of right atrial function by strain and strain rate imaging in patients with heart failure. AB - OBJECTIVES: We sought to evaluate the regional longitudinal strain/strain rate profiles in the right atrial wall to quantify right atrial function in systolic heart failure patients. BACKGROUND: According to previous studies on the deformational properties of the left atrium, the systolic strain and strain rates represent the atrial reservoir function and the early and late diastolic strain rates show the conduit and booster functions, respectively. METHODS: Thirty patients with a diagnosis of heart failure (left ventricular ejection fraction < or = 35%) scheduled for right heart catheterization were enrolled. Echocardiography was performed to obtain right atrial deformation indices just before the procedure. The control group consisted of 32 healthy adults matched for age and sex. The deformity indices obtained consisted of the right atrial peak systolic strain (RAS), right atrial peak systolic strain rate (RASSR), right atrial early diastolic strain rate (RAEDSR), and right atrial late diastolic strain rate (RALDSR). RESULTS: The right atrial deformation indices were significantly compromised in the heart failure patients versus the normal subjects (RAS: 68.5 +/- 53.9 vs 189.3 +/- 61.2, P = 0.000; RASSR: 2.9 +/- 1.9 vs. 5.3 +/- 1.5, P = 0.000).There was a significant correlation between the RAS and RASSR and cardiac output (RAS: r = 0.5, P = 0.005; RASSR: r = 0.5, P = 0.003), and cardiac index (RAS: r = 0.6, P = 0.001; RASSR: r = 0.6, P = 0.001). CONCLUSION: In light of our findings, we conclude that a diminished RA function, as assessed by strain imaging, plays a critical role in the pathophysiological process of heart failure patients. PMID- 22299385 TI - Coronary flow reserve in patients with aortic stenosis and nonobstructed coronary arteries. AB - OBJECTIVE: Patients with moderate and severe aortic stenosis (AS) and without obstructive epicardial coronary disease have been shown to have an impairment of coronary flow velocity reserve (CFVR). Recently, it has been shown that CFVR is an independent predictor for future cardiovascular events in AS patients. We investigated parameters representing left ventricular (LV) mass and wall thickness, diastolic dysfunction, LV workload and haemodynamic indexes of AS severity to determine which contributes the most to impaired CFVR in patients with AS and a nonobstructed coronary angiogram. METHOD AND RESULTS: A total of 77 patients with moderate or severe AS, mean age 65.66 +/- 11.02 y (57.14% males), were enrolled in this prospective study. All patients had standard Doppler-echo study, coronary angiography and adenosine-stress transthoracic Doppler-echo for CFVR measurement. We took 2.5 as a cut-off value for impaired CFVR. Univariate analysis showed that aortic valve area (AVA), maximal velocity (Vmax), mean pressure gradient (Pmean), energy loss index (ELI), aortic valve resistance (AVR) and stroke work loss (SWL) were associated (P = 0.05) with impaired CFVR. Multivariate analysis showed that AVR was the best predictor of impaired CFVR (RR 0.900, Cl: 0.983-0.997, P = 0.007). Using ROC analysis, the AVR value of 211.22 dynes x s x cm(-5) had the highest accuracy in predicting the impaired CFVR (AUC 0.681, P=0.007, sensitivity 72%, specificity 52%, CI: 0.561-0.800). CONCLUSION: Haemodynamic indices of AS severity, together with LV workload parameters, are the main determinants of CFVR. Among all parameters, AVR is the strongest predictor of CFVR in patients with moderate or severe AS and a nonobstructed coronary angiogram. PMID- 22299386 TI - Determinants of mortality in patients with heart failure and atrial fibrillation during long-term follow-up. AB - BACKGROUND: Heart failure (HF) and atrial fibrillation (AF) often occur together. Both are independently associated with an increased mortality. Clinical parameters associated with mortality in patients with HF such as left ventricular ejection fraction (LV-EF) and New York Heart Association (NYHA) functional class are influenced by AF. If these parameters are still determinants of mortality when HF is complicated by AF, or if other parameters determine mortality in this case is unknown. METHODS AND RESULTS: We studied 173 consecutive HF patients (mean age 67 +/- 12 years, 30% female) in New York Heart Association (NYHA) functional class 2.6 +/- 0.8 with left ventricular systolic dysfunction (ejection fraction 45%) and AF. Mortality was 42% after a mean follow-up of 41 months. Age (OR 1.04, CI 1.01-1.07, P = 0.003), chronic obstructive pulmonary disease (OR 2.07, Cl 1.15-3.73, P = 0.015), elevated serum creatinine at admission (OR 1.25, Cl 1.01-1.54, P = 0.033), prolongation of QRS duration (OR 1.02, CI 1.01-1.54, P= 0.001), decreased serum sodium at admission (OR 0.94, Cl 0.89-0.99, P = 0.026) and oral anticoagulation (OR 0.59, Cl 0.36-0.99, P = 0.046) were independently associated with mortality when assessed with multivariable Cox proportional hazard analysis. Importantly, mortality was not associated with NYHA functional class or left ventricular ejection fraction (LVEF). CONCLUSIONS: Elevated creatinine levels, decreased serum sodium levels, prolongation of QRS duration and the presence of COPD are associated with long-term mortality after hospitalization in patients with HF and AF. Oral anticoagulation is associated with better survival. LVEF and NYHA functional class are no reliable mortality markers in this patient population. PMID- 22299387 TI - Carotid intima media thickness and cardiometabolic risk associates in Turkish adults. AB - OBJECTIVE: Carotid intima media thickness (CIMT) is a strong predictor of future vascular events. However, data for Turkish individuals are limited and the association between cardiometabolic risk factors and CIMT has not been studied before.Therefore, we sought to investigate the CIMT and cardiometabolic risk associates in a large cohort of Turkish adults. METHODS AND RESULTS: The study was conducted on 2230 participants (1427 women, 803 men with a mean age of 49). The participants underwent a Doppler Ultrasound examination of CIMT. Mean CIMT was 0.61 +/- 0.19 mm. Age- and sex-adjusted partial correlation analysis revealed that only systolic blood pressure and smoking amount was significantly correlated with CIMT. Receiver operator characteristics (ROC) calculations showed that age had the best area under the curve (AUC = 0.84), smoking had the best sensitivity (86%) and diastolic blood pressure (> 88 mmHg) had the best specificity (74%) in predicting a person with thickened carotid intima media (> 0.8 mm). Independent predictors of thickened carotid intima media were hypertension [(odds ratio (OR) = 2.74; 95% confidence interval (CI) = 1.663-4.53; P value < or = 0.001)], systolic blood pressure [OR = 1.01; 95% CI = 1.002-1.022; P value = 0.022] and age [OR = 1.11; 95% CI = 1.079-1.136; P value < or = 0.001). CONCLUSION: Age, systolic blood pressure and smoking amount (pack/year) were the only age- and sex adjusted associates of CIMT. Age had the best AUC in ROC analysis predicting thickened carotid artery intima media. Hypertension, systolic blood pressure and age were independent predictors of high CIMT in Turkish adults. PMID- 22299388 TI - Evaluation of a novel paclitaxel-eluting stent with a bioabsorbable polymeric surface coating in the porcine artery injury model. AB - PURPOSE: Drug-eluting stents (DES) are unique in allowing sustained release after a single short intervention. The challenge with DES still remaining is the optimal combination of a biocompatible drug-eluting matrix including an antiproliferative drug. We studied the role of a novel paclitaxel-eluting stent with a bioabsorbable polymer coating in preventing vascular restenosis in the porcine artery injury model. MATERIAL AND METHODS: Bare metal stents (BMS); polymer-coated-only stents (POLY); and polymer-based paclitaxel-eluting stents (PACL) were randomly implanted in pig femoral arteries. The dose density of paclitaxel was 1 microg/mm2 with in vitro studies demonstrating a gradual elution over a course of 6 month. RESULTS: After 1-, 3- and 6-month follow-up, respectively, the animals underwent angiographic restudy and were terminated for histomorphometrical and histopathological analyses. At 1 month, the PACL group had the lowest histological percent stenosis when compared to the BMS and POLY groups (20 +/- 4% vs 39 +/- 6% and 41 +/- 6%, respectively, P < 0.05). At 3 months, the PACL group still presents the lowest level of histological percent stenosis among the three groups (27 +/- 6% vs 50 +/- 10% and 46 +/- 5%, respectively, P < 0.01). Six months later, the PACL group showed a similar histological percent stenosis as the BMS and POLY groups (44 +/- 9% vs 56 +/- 11% and 53 +/- 9%, respectively, P = 0.145). CONCLUSIONS: This study shows favourable vascular compatibility and efficacy for a novel DES to inhibit in-stent neointima formation and preserve lumen area in the porcine artery model. PMID- 22299389 TI - Endothelial progenitor cells are associated with plasma homocysteine in coronary artery disease. AB - OBJECTIVE: Little is known about the association between plasma homocysteine (Hcy) and endothelial progenitor cells (EPCs) in coronary artery disease (CAD). METHODS: Blood mononuclear cells were isolated from CAD (n = 30) patients and non CAD controls (n = 30). Flow cytometric analysis and an in vitro culture system was used to evaluate the number and function of the EPC. Plasma homocysteine (Hcy) concentration was measured by an automated fluorescence polarization immunoassay. RESULTS: Hcy level was higher in CAD than in non-CAD (13.69 +/- 4.48 vs 9.34 + 2.31 pmol/L, P < 0.01). The number of circulating EPCs from CAD was decreased compared with non-CAD (58.7 +/- 10.6 vs. 94.3 +/- 15.1 cells/ml, P < 0.01). This decrease of EPCs in CAD was also detected (33.5 +/- 6.9 vs. 55.9 +/- 9.7 EPCs/x200 field; P < 0.01) in an in vitro culture system. The numbers of circulating and differentiated EPCs were both inversely correlated with Hcy. EPCs from CAD were significantly impaired in their migratory capacity and ability to adhere to fibronectin. CONCLUSIONS: We observed the correlation between Hcy level and EPC number, and also found an increased Hcy level in CAD patients. It will be interesting to reveal the underlying mechanisms contributing to the correlation and examine the possible causal relationship between Hcy levels and CAD. PMID- 22299390 TI - The role of speckle tracking imaging in the noninvasive detection of acute rejection after heterotopic cardiac transplantation in rats. AB - OBJECTIVE: Acute cardiac allograft rejection continues to be the cause of graft loss and contributes to the morbidity and mortality after cardiac transplantation. Repetitive endomyocardial biopsies are necessary to monitor the effects of immunosuppressants after cardiac transplantation. In this study, we investigate whether speckle tracking imaging (STI) is a valuable method in assessing acute cardiac rejection. METHODS AND RESULTS: Hearts from Brown Norway rats or Lewis rats were transplanted into other Brown Norway rats. Isografts and groups of allografts, either untreated or treated with cyclosporine A (CsA) at a low dose (3 mg x kg(-1) x d(-1)) or a high dose (10 mg x kg(-1) x d(-1)), were compared 7 days after transplantation. Echocardiography-derived left ventricular post wall thickness was increased only in untreated allografts.The left ventricular ejection fraction was significantly lower in the allografts compared with the isografts, but allografts treated without or with low-dose CsA showed similar results. The radial velocity and systolic radial strain rate showed a lower value in untreated allografts than other grafts, but there is no significant difference between allografts treated with high- or low-dose CsA and isografts. The circumferential strain and circumferential strain rate were comparable among the 4 groups. However, the radial strain exhibited a clear gradient in these groups (2.8 +/- 1.3 in untreated allografts, 5.2 +/- 10.9 in allografts treated with low-dose CsA, 6.3 +/- 1.8 in allografts treated with high dose CsA, and 12.7 +/- 7.9 in isografts, P < 0.001). CONCLUSIONS: STI is able to offer a noninvasive method for detecting transplant allograft rejection. PMID- 22299391 TI - Analysis of beta1 and beta2-adrenergic receptors polymorphism in patients with apical ballooning cardiomyopathy. AB - OBJECTIVE: The aim of our study was to analyse the frequency of beta1 and/or beta2 adrenergic receptor polymorphisms in patients with takotsubo cardiomyopathy (TTC). METHODS AND RESULTS: beta1 and/or beta2 adrenergic receptor polymorphisms in 61 patients with TTC were compared with 109 controls. The beta1 adrenoreceptor (amino acid position 389) genotype frequencies were significantly different in the two groups; assuming a recessive model for the allelic variant coding for Arg on this position, the odds ratio was 3.14, 95% Cl 1.55-6.37 (P = 0.0015). The beta2 adrenoreceptor amino acid position 27 genotype was significantly different and assuming a recessive model for the allelic variant coding for Gln on this position, the odds ratio was 0.29, 95% Cl 0.12-0.74 (P = 0.009). CONCLUSIONS: This study showed for the first time an association between TTC phenotype and beta1 adrenoreceptor gene polymorphisms. Beta adrenoreceptors gene polymorphisms are probably disease modifiers, and any risk estimate should be based on a combination of genotypes and on interactions with other genes and environmental features. PMID- 22299392 TI - Lifestyle modifications after acute coronary syndromes in a subset of the AMI Florence 2 Registry. AB - OBJECTIVE: The aim of this study was to evaluate the adherence to recommendations for secondary prevention of cardiovascular diseases in patients with acute coronary syndromes (ACS). METHODS AND RESULTS: Physical examination, a careful medical interview with assessment for lifestyle habits, adherence to pharmacological therapy and blood analyses were performed in 130 patients at the time of the acute event and after 6 months of follow-up. At follow-up examination, 7 patients persisted to smoke (5.4%), 41 (31.5%) continued to have high blood pressure, 34 (26.1%) had high levels of total cholesterol, 38 (29.2%) high levels of triglycerides, 64 (49.2%) high levels of LDL-cholesterol and 46 (35.4%) low levels of HDL-cholesterol. Despite all treatments no significant change occurred. A high percentage of patients (47%) reported a lower daily consumption of fruit and vegetables with respect to the recommended daily portions, nearly the whole population (92.3%) did not reach the recommended portions of legumes per week recommended, and a consistent percentage of patients (81.5%) did not consume fish twice a week, as recommended. CONCLUSION: These findings demonstrate the difficulty of modifying the lifestyle habits in patients with ACS. PMID- 22299393 TI - Thoracoscopic left ventricular lead implantation. AB - OBJECTIVE: Cardiac resynchronization therapy is a therapeutic option in patients with chronic heart failure. Epicardial lead implantation for biventricular pacing is usually the method of second choice after failed coronary sinus cannulation. The present study describes an initial experience with minimally invasive surgical lead implantation using thoracoscopy. METHODS: Since August 2008, a total of 17 patients (mean age 69.6 + 11.1 years) with congestive heart failure, NYHA functional class 3.1 +/- 0.4, and depressed ejection function (24.8% +/- 5.7%) were referred for surgery because of failed left ventricular lead implantation through the coronary sinus. Under single-lung ventilation and video assisted thoracoscopy, epimyocardial steroid-eluting screw-in leads were implanted on the left ventricular free wall. RESULTS: There were no in-hospital deaths or major co-morbidities. The mean skin-to-skin operating time was 115.9 +/ 32.1 min, and the post-operative average length of stay was 8.4 +/- 2.5 days. Intraoperative acute threshold capture of the left ventricular lead was 0.88 +/- 0.54 V/0.5 ms, and the value of lead impedance was 434.7 +/- 110.8 Omega. Extension to a small thoracotomy was necessary in 1 patient to stop epicardial vein bleeding. CONCLUSION: Minimally invasive left ventricular lead implantation is a safe procedure with excellent acute threshold capture. PMID- 22299394 TI - The anti-arrhythmic effects of prednisone in patients with sarcoidosis. AB - Atrial fibrillation (AF) affects 2.3 million people in the United States and is currently the most common cardiac arrhythmia. Its overall prevalence is only increasing as the population ages. The classical risk factors for developing AF include hypertension, valvular disease, ischemic cardiomyopathy, and thyroid disease. In some patients with AF, an underlying cardiovascular pathology is not identified and the etiology remains unknown. Treatment modalities for AF typically include rate control medications, antiarrhythmics and radio frequency ablation (RFA), each of which is accompanied by its own risk of complications. We report a case of symptomatic AF that was refractory to multiple antiarrhythmics and an RFA procedure which resolved with prednisone. In this case, AF was associated with cardiac sarcoidosis, a disorder that is thought to be due to granulomatous involvement of the myocardium and increased systemic inflammation. PMID- 22299395 TI - H1N1 virus infection associated with acute myocardial infarction in a young patient without coronary artery disease--first reported case. AB - Swine-origin influenza A (H1N1) virus was identified in March of 2009 in Mexico and the United States. The virus spread rapidly, becoming pandemic by June. Previous studies examined the role of influenza infection in cardiovascular disease, however, we present the first case of an acute myocardial infarction in a healthy patient specifically associated with the novel viral infection. This case underscores the importance of prompt diagnosis and treatment as well as vigilance on behalf of health care workers in treating patients affected with influenza A (H1N1). Consideration of this previously undescribed pathology may play a significant role in the coming debates over vaccines and access. PMID- 22299396 TI - Transient midventricular ballooning syndrome. an atypical presentation of takotsubo cardiomyopathy. AB - A 72-year-old woman without cardiovascular history presented with acute substernal chest pain and dyspnoea. The electrocardiogram was normal, but the blood test analyses showed an elevated troponin T level. Emergency coronary angiography revealed normal epicardial coronary arteries, but the left ventriculogram demonstrated midventricular dilatation and akinesis with well preserved contractility of the apex and base. The patient was diagnosed as having an atypical presentation of takotsubo cardiomyopathy. She was treated with a beta blocker and an ACE inhibitor and recovered well. A follow-up echocardiogram at 2 months showed normalization of the wall motion abnormality. PMID- 22299397 TI - Factors associated with acute renal failure in falciparum malaria infected patients. AB - To identify factors associated with acute renal failure among patients with severe falciparum malaria (MARF), we studied 189 severe malaria patients admitted to the Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, in Bangkok, Thailand. Among these, 63 had MARF, and 126 did not. Baseline clinical demographics and laboratory variables were evaluated with univariate analysis. Logistic regression was used to ascertain adjusted odds ratios. By univariate analysis, factors associated with MARF included male gender, fever duration > 4 days, patients who lived in a non-endemic area prior to malaria infection, body mass index > 18.5 kg/m(2), oliguria, abdominal pain, impaired consciousness, jaundice, anemia, liver enlargement, total white blood cell count > 10x10(9)/1, total bilirubin > 3 mg/dl, aspartate aminotransferase > 120 U/l, alanine aminotransferase > 120 U/l, albumin < 3 g/dl, fever clearance time >72 hours, and parasite clearance time > 72 hours. A hemoglobin > 10 g/dl, patients living in a malaria endemic area, non-oliguria on the day of admission, and splenomegaly were negatively associated with MARF. After multivariate logistic regression, oliguria during the first 24 hours of admission and a history of living in a nonendemic area prior to malarial infection were factors associated with MARF. We conclude the most significant factors associated with MARF were oliguria on the day of admission and living in a non-endemic area prior to malaria infection. PMID- 22299398 TI - Humoral immune responses to Plasmodium vivax subtelomeric transmembrane proteins in Thailand. AB - Plasmodium vivax subtelomeric transmembrane protein (PvSTP) is a homolog of P. falciparum SURFIN4.2', a protein exposed on the parasite-infected erythrocyte (iE) surface, and is thus considered to be exposed on P. vivax-iE. Because antibodies targeting antigens located on the surface of P. falciparum-iE, such as P. falciparum erythrocyte membrane protein 1, play an important role in regulating the course of disease, we evaluated the presence of antibodies in P. vivax-infected patients against two PvSTP paralogs, PvSTP1 and PvSTP2. Recombinant proteins corresponding to cysteine-rich domain (CRD) of the PvSTP extracellular region and the cytoplasmic region (CYT) were generated and used for the enzyme-linked immunosorbent assay. Plasma samples (n = 70) reacted positively with recombinant PvSTP1-CRD (40%), PvSTP1-CYT (31%), PvSTP2-CRD (27%), and PvSTP2 CYT (56%), suggesting that PvSTP1 and -2 are naturally immunogenic. Specific response against either PvSTP1 or PvSTP2 indicates the existence of specific antibodies for either PvSTP1 or -2. PMID- 22299399 TI - High prevalence of pfcrt K76t mutants among Plasmodium falciparum isolates from Sabah, Malaysia. AB - Chloroquine (CQ) remains the first line drug for the prevention and treatment of malaria in Malaysia in spite of the fact that resistance to CQ has been observed in Malaysia since the 1960s. CQ-resistance is associated with various mutations in pfcrt, which encodes a putative transporter located in the digestive vacuolar membrane of P. falciparum. Substitution of lysine (K) to threonine (T) at amino acid 76 (K76T) in pfcrt is the primary genetic marker conferring resistance to CQ. To determine the presence of T76 mutation in pfcrt from selected areas of Kalabakan, Malaysia 619 blood samples were screened for P. falciparum, out of which 31 were positive. Blood samples were collected on 3 MM Whatman filter papers and DNA was extracted using QIAmp DNA mini kit. RFLP-PCR for the detection of the CQ-resistant T76 and sensitive K76 genotype was carried out. Twenty-five samples were shown to have the point mutation in pfcrt whereas the remaining samples were classified as CQ-sensitive (wild-type). In view of the fact that CQ is the first line anti-malarial drug in Malaysia, this finding could be an important indication that treatment with CQ may no longer be effective in the future. PMID- 22299400 TI - Morphological characteristics of developmental stages of Acanthamoeba and Naegleria species before and after staining by various techniques. AB - Seven stains were studied to determine the best color and contrast for staining the developmental stages of free living pathogenic Acanthamoeba and Naegleria species. The acid-fast bacilli stain (AFB) produced a blue color without contrast; trichrome-eosin and modified Field's showed various color contrasts; Giemsa, iron-hematoxylin, modified AFB and Gram produced only one color which distinguished the nucleus, nucleolus, cytoplasm, food- and water-vacuoles. The motile organs (acanthopodia, pseudopodia, lobopodia and flagella) were also clearly differentiated but produced a similar color as the cytoplasm. These motile organelles were first induced by incubating at 37 degrees C for at least 15 minutes and then fixing with methanol in order to preserve the protruding morphology prior to staining. The trichrome-eosin and iron-hematoxylin stains showed good color contrast for detecting all three stages, the trophozoite, cyst and flagellate; Giemsa and Gram stained the trophozoite and flagellate stages; the modified Field's and modified AFB stains stained only the trophozoite stage. Depending on the purpose, all these stains (except the AFB stain) can be used to identify the developmental stages of Acanthamoeba and Naegleria for clinical, epidemiological or public health use. PMID- 22299401 TI - Comparison of three antigen preparations to detect Trichinellosis in live swine using IgG-ELISA. AB - A swine infected with Trichinella spiralis is a source of transmission to human through consumption of raw or improperly cooked pork. Detection of larvae is suitable for carcasses, so that pigs in households or farms can be examined serologically for trichinellosis. This study compared antigens, crude (CAg), excretory-secretory (ESAg) and surface (SAg), for their potential use in IgG ELISA. Serum samples were collected from 5 experimentally infected swine with T. spiralis (pTs), 147 positive cases of 9 other parasitic infections, 12 mixed infections of other parasites, and 35 normal controls. At the same 100% sensitivity, specificity of tests was in a range of 98-77%. ESAg was the best source of antigen with specificity of 98.3% at cut-off value of 0.439. False positives included coccidiasis (1/86) and mixed infections (2/39). For CAg, trichuriasis (2/11), coccidiasis (5/86), and mixed infections (8/39) gave cross reactions and some of these samples had OD values far above cut-off value of 0.332. Cross-reactions of SAg were Oesophagostomum spp-like GI-nematode infection (1/1), unidentified GI-nematode infections (2/3), trichuriasis (5/11), coccidiasis (29/86) and mixed infections (4/39). Thus, ESAg has the highest potential in serodiagnosis, with antibody to T. spiralis in pigs being detected at the earliest 16 day post-infection. However, crude antigen demonstrated a good specificity at 91.8%, and this antigen has a potential to be used as a detection of choice for swine trichinellosis, but the antigen preparation must be improved for higher specificity. PMID- 22299402 TI - Microfilaria and filarial granulomas from fine needle aspirates: a study of 25 cases. AB - The objective of this study was to assess the role of fine needle aspiration cytology (FNAC) for the diagnosis of filariasis. Cytological smears were studied during 2006-2009. Twenty-five cases with microfilaria were detected: 7 from lymph nodes, 5 from soft tissue, 4 from effusion fluids, 3 from breast tissue, 2 from liver tissue, 1 each from thyroid tissue, a cervicovaginal smear, a hernial sac and a spermatic cord cyst. Embryonated adult worms were seen in four cases and eosinophils were seen in 3 cases. In endemic areas the diagnosis of filariasis should be considered in the differential diagnosis of swelling. This study highlights the importance of screening smears for parasites even in the absence of clinical indications and shows eosinophils are not mandatory to diagnose microfilaria. PMID- 22299403 TI - A rare case of ocular onchocerciasis in India. AB - Onchocerca volvulus is a spirurid nematode that mainly affects the rural poor of Sub-Saharan Africa, Yemen and parts of Central and South Africa. River blindness, caused by Onchocerca volvulus, is considered to be the second commonest infectious cause of blindness worldwide. We report a rare case of ocular onchocerciasis where a live adult worm was extracted from the eye of a patient from a nonendemic region. The worm was identified as Onchocerca volvulus based on morphological features. The patient was treated with Ivermectin (0.2 mg/kg). At six months follow-up she had complete remission of symptoms. PMID- 22299404 TI - Serological and molecular tools to detect neurologic parasitic zoonoses in rural Cameroon. AB - Parasitic helminthiases, such as toxocariasis, cysticercosis and paragonimiasis are a public health threat, since they can affect the brain leading to neurological disorders. Epilepsy and paragonimiasis are common in southwestern Cameroon. We reviewed the literature for studies using antigens to diagnose toxocariasis, cysticercosis, and paragonimiasis. Serology revealed that 61 (36.3%), 26 (15.5%) and 2 (1.2%) of 168 persons examined [78 males (15.2 +/- 8.2 years old), 90 females (12.9 +/- 5.9 years old), 143 persons < 20 years old] had antibody responses to toxocariasis, paragonimiasis and cysticercosis, respectively. Of the 14 people with epilepsy, 5 were seropositive for Toxocara antigens and 1 was positive for both Toxocara and Paragonimus antigens. Two children were serologically confirmed to have cysticercosis. Serologic screening for cysticercosis may be feasible to detect asymptomatic cysticercosis in children in endemic areas leading to early treatment. The causative Paragonimus species was confirmed to be P. africanus by molecular sequencing. Education, screening and confirmation test for these diseases may be needed for control in Cameroon. PMID- 22299405 TI - Demodicosis among university medical students in Malaysia and the effects of facial cleanser and moisturizer usage. AB - Demodicosis is an infestation of the skin with Demodex, an ectoparasite commonly found on the face. A cross-sectional study was conducted to detect the presence of the ectoparasite and the outcome of facial cleanser and moisturizer usage on its infestation. Universal sampling was performed among 390 medical students, age 20-25 years old in the Klang Valley of Malaysia. The biodata of the participants and information on the use of facial cleanser and moisturizer were obtained through questionnaire. Skin samples were obtained using both skin scraping and cellophane tape method and were subsequently examined directly by microscopy. The results show an overall prevalence of 17.2%. Males (21.5%) were affected more often than females (12.8%) (p = 0.022). There were no significant differences in the prevalence of the ectoparasite among different ethnic groups, age-groups and the presence of existing facial problems among the subjects. A lower infestation rate (11.45%) was found to be associated with the use of a moisturizer (p = 0.033). Both species of ectoparasites that infest man, Demodexfolliculorum and D. brevis, were detected in this study either as single or mixed infestations. PMID- 22299406 TI - Utility of a set of conserved mitochondrial cytochrome oxidase subunit I gene primers for Mansonia annulata identification. AB - DNA-based identification system using the mitochondrial cytochrome oxidase subunit I (COI) gene has enabled validation of many species in certain taxonomic groups. These primer combinations were able to work universally across Insecta. Here, a set of three primer pairs were successful in amplifying COI of Mansonia annulata mosquito, a potential vector of Brugia malayi. By merging all three amplicons the whole COI was obtained. Primer pair TY-J-1460/C1N2087 amplified 5' region of COI, LepF1/LepR1 the central and C1J2090/TL2N3014 the 3' region, generating COI amplicons of 650, 700 and 950 base pairs, respectively. When Ma. annulata sequences were compared with those from online sources, they formed a cluster group that is clearly distinct from other allied species. PMID- 22299407 TI - Competitive suppression between chikungunya and dengue virus in Aedes albopictus c6/36 cell line. AB - Aedes albopictus C6/36 cell line was used to evaluate dengue virus serotype-3 (DENV-3) and chikungunya virus (CHIKV) co-infection. Virus infection was determined using a one-step duplex reverse transcriptase polymerase chain reaction (D- RT-PCR). D-RT-PCR was positive for both viruses when equal multiplicity of infection (MOI) was utilized. Co-infection with different titers between a higher CHIKV titer (MOI = 1.0) than DENV-3 titer (MOI = 0.1) showed similar results with that of equal titer. However, co-infection with a lower CHIKV titer (MOI = 0.1) than DENV-3 titer (MOI = 1.0) revealed positive results for only dengue virus infection, suggesting DENV competitive suppression of CHIKV. This competitive suppression occurred in mixed-infection samples but not in individually double infection (super infection) samples which produced both dengue and chikungunya virus progenies. Both virus replications depend on the amount of virus titer rather than serial infection. These findings have provided information regarding pathogen-pathogen interaction in host cell, which could be used to predict outbreaks, and to develop virus detection and vector control. PMID- 22299408 TI - Distribution of cave-dwelling phlebotomine sand flies and their nocturnal and diurnal activity in Phitsanulok Province, Thailand. AB - An entomological survey of sand flies was conducted in Naresuan Cave in Noen Maprang District, Phitsanulok Province, during November 2009 to December 2010. A total of 10,115 cave-dwelling sand flies were collected with CDC light traps nocturnally (06:00 AM and 06:00 PM) and diurnally (06:00 PM and 06:00 AM). The ratio between male and female sand flies was 1:1.3 (4,363:5,752). The ratio between the number of sand flies caught nocturnally and diurnally was 2.6:1 (7,268:2,847). In this study, 13 species belonging to 4 genera were identified, of which 4 belonged to the genus Phlebotomus, 7 to Sergentomyia, 1 to Nemopalpus and 1 to Chinius. An abundance of species were observed: Nemopalpus vietnamensis (49.15%), P. argentipes (20.15%), C. barbazani (15.79%), P. teshi (9.53%), and S. anodontis (3.21%). Less common species (<1%) were S. barraudi (0.63%), P. stantoni (0.57%), S. dentata (0.49%), S.quatei (0.17%), P. philippinensis gouldi (0.12%), S.silvatica (0.10%), S. gemmea (0.05%), and S. iyengari (0.04%). The predominant species in the Naresuan Cave was Nemopalpus vietnamensis (49.15%). The data demonstrates variability in sand fly prevalence, species composition, and relative abundance in caves. P. argentipes was found throughout the day in the caves, which is important because it is believed to be the Leishmania spp vector. This study highlights the diurnal activity of the sand fly and the day time risk of leishmaniasis. In conclusion, although leishmaniasis has not been reported in Phitsanulok, there should be heightened awareness of infection in these areas with vectors of the protozoa. PMID- 22299409 TI - Cavernicolous species of phlebotomine sand flies from Kanchanaburi Province, with an updated species list for Thailand. AB - During 2008-2009 2,401 Phlebotomine sand flies were collected in 14 limestone caves in Kanchanaburi Province, Thailand to determine the prevalence and type of cavernicolous species that have the potential to be leishmaniasis vectors. Twenty species belonging to the genera Chinius, Nemopalpus, Phlebotomus and Sergentomyia were identified. An additional man-biting species, P. major major was recorded for the first time in Thailand. Ecological observations of the habitats were made. It is expected the diversity of cavernicolous sand flies is more than currently known. An updated list of 26 phlebotomine species for Thailand is provided. PMID- 22299410 TI - Hepatitis B among pregnant women attending health care facilities in rural Bangladesh. AB - This study assessed hepatitis B prevalence among pregnant women attending health care facilities in rural Bangladesh. Blood samples were collected from 480 participants. HBsAg was positive in 0.4% of subjects, anti-HBc was positive in 21.5% and anti-HBs was positive in 8.5% of subjects. HBsAg was more prevalent among the older age group. Hepatitis B has a low prevalence among pregnant women in rural Bangladesh. Existing hepatitis B vaccination schedule in the Expanded Program on Immunization (EPI) to vaccinate the children in rural Bangladesh is appropriate. PMID- 22299411 TI - Effectiveness of fixed-dose combination stavudine, lamivudine and nevirapine (GPO VIR) for treatment of naive HIV patients in Thailand: a 3-year follow-up. AB - Generic fixed dose combination stavudine (d4T), lamivudine (3TC) and nevirapine (NVP), named GPO-VIR is recommended in the HIV treatment guidelines for Thailand. The long term effectiveness and adverse effects of this drug combination for the treatment of HIV were evaluated in an ambispective study at Bamrasnaradura Infectious Diseases Institute, Nonthaburi Province, Thailand from March 2002 to January 2006. A total of 152 adult treatment naive HIV patients who had received at least 12 months of GPO-VIR were enrolled. The median (IQR) CD4 cell count increased from 23 (8-94) cells/microl at baseline to 126 (38-180), 136 (98-189), 199 (141-255) and 334 (243-414) cells/microl at 3, 6, 12 and 24 months (p < 0.001), respectively. The median (IQR) percentage of body weights increased from baseline by 3.0% (0.3-6.3), 6.2% (2.2-9.3), 7.3% (3.9-10.9) and 8.1% (3.4-11.9) at 3, 6, 12 and 24 months, respectively and then remained at a plateau until the end of the 3-year study. The occurrence of new opportunistic infections decreased significantly (p < 0.001) with GPO-VIR treatment. Drug resistance occurred in 5 cases (3.3%) with a median (IQR) time of 18.0 (16.5-32.5) months to occurrence. Adverse effects included hypercholesterolemia (43.2%), lipodystrophy (35.5%), hypertriglyceridemia (25%), hypertension (13.1%), peripheral neuropathy (11.9%), hyperlactatemia (2.6%) and lactic acidosis (1.3%). Thirty-six patients (27%) switched from GPO-VIR to other anti-retroviral drugs regimens due to lipodystrophy. This study showed GPO-VIR had clinical and immunological benefits, but one-third of patients had adverse effects. PMID- 22299412 TI - Establishment of a molecular diagnostic system for detecting human papillomavirus in clinical samples in Sri Lanka. AB - Human papillomavirus (HPV) is associated with variety of clinical conditions that range from innocuous lesions to cancer in both men and women. Consensus primer mediated PCR assays have enabled screening for a broad spectrum of HPV types. We have established a molecular diagnostic system for detecting HPV DNA in clinical samples from STD clinics in Sri Lanka and compared the efficacy of three different primer sets, MY09/11, GP5+/6+ and CPI/IIG primer sets, to determine which primer set or combination of primers is most efficacious in screening for HPV. Cervical and urethral swabs were obtained from 51 patients who were suspected of having HPV. The presence of HPV DNA in swabs was detected by MY09/11 PCR (33%), GP5+/6+ PCR (72%) and CPI/IIG PCR (57%) primers. HPV DNA was detected in 23% of samples by all three methods, in 43% by any two methods, and in 6% only by GP5+/6+ primer set. GP5+/6+ PCR alone was capable of detecting the most number of HPV positives but, any single PCR method for the detection of HPV may underestimate the true prevalence of HPV in clinical samples. Nested PCR assay with MY09/11 and GP5+/6+ primer sets had higher sensitivity than singleplex PCR but, due to the risk of cross contamination in employing nested PCR, it was concluded that GP5+/6+ PCR is more suitable for HPV DNA detection in epidemiologic and clinical follow-up studies in Sri Lanka. PMID- 22299413 TI - Investigating user-friendliness of the sexual and reproductive health services among youth in Botswana. AB - The objectives of this study were to investigate the extent of user-friendliness of sexual reproductive health services offered in Botswana. A cross-sectional study was conducted among 110 youth. A self-administered questionnaire was used to assess the friendliness of the health providers, health facility and program design using a 5-point Likert scale. The mean age of the participants was 22.1 (SD = 3.5) years. A third (33%) of participants perceived the referral system as not being youth-friendly and/or not adequate. The majority of participants (84.2%) agreed or strongly agreed that the health providers greeted youth receiving sexual and reproductive health services in a polite manner with 89.2% either agreeing or strongly agreeing that health providers told youth to return if they had concerns and 91.9% encouraging them to ask questions. More than a quarter (26%) indicated the health providers had no respect for youth; 27% of the response variables were rated lowest among the variables used to assess the friendliness of the health facility. Almost two-thirds (64%) of respondents indicated the waiting time was excessive. Fifty percent felt the sex and reproductive health services had inadequate publicity. Health provider attitudes had the greatest impact on youth perceptions (Odd ratio = 11.81; p < 0.05). Although the sexual and reproductive health service in Botswana is doing well, there are still some few weaknesses that need to be addressed, particularly working hours, and publicity of the sexual reproductive health services and information. PMID- 22299414 TI - Tuberculosis treatment with mobile-phone medication reminders in northern Thailand. AB - Thailand's implementation of the Directly Observed Treatment, Short course (DOTS) strategy to increase tuberculosis (TB) control program efficacy has not achieved the World Health Organization (WHO) TB key targets. We defined two TB control models in the study. Patients in Model 1 were treated with a conventional DOTS strategy and in Model 2, patients were treated the same as Model method 1 but were given a phone call reminder to take their medication. Multi-drug resistant tuberculosis (MDR-TB) and non-MDR-TB patients were randomized into either Model 1 or 2. Treatment outcomes were given as cure rates, completion rates, failure rates or success rates at 18 months in the MDR-TB group and 6 months in the non MDR-TB group. The sputum conversion rate at 1 month were evaluated for both groups. In the MDR-TB group, the sputum conversion rate was 20% (95% CI 8-45) in Model 1 and 90% (95% CI 73-98) in Model 2 (p < 0.001). In the non-MDR-TB group, the sputum conversion rate was 52% (95% CI 36-70) in Model 1 and 37% (95% CI 22 56) in Model 2 although the difference was not significant (p = 0.221). The Model 2 success rates were significantly higher (73.7%, 96.7%) in both the MDR-TB and non-MDR-TB groups (p < 0.001, p = 0.047). The MDR-TB rate in northern Thailand decreased from 4.1% during April-September 2008 to 1.8% during April-September 2009. Further study of the association between implementation of Model 2 and MDR TB incidence reduction needs to be carried out. PMID- 22299415 TI - Efficient heterologous expression and one-step purification of fully active c terminal histidine-tagged uridine monophosphate kinase from Mycobacterium tuberculosis. AB - Tuberculosis has long been recognized as one of the most significant public health problems. Finding novel antituberculous drugs is always a necessary approach for controlling the disease. Mycobacterium tuberculosis pyrH gene (Rv2883c) encodes for uridine monophosphate kinase (UMK), which is a key enzyme in the uridine nucleotide interconversion pathway. The enzyme is essential for M. tuberculosis to sustain growth and hence is a potential drug target. In this study, we have developed a rapid protocol for production and purification of M. tuberculosis UMK by cloning pyrH (Rv2883c) of M. tuberculosis H37Rv with the addition of 6-histidine residues to the C-terminus of the protein, and expressing in E. coli BL21-CodonPlus (DE3)-RIPL using an auto-induction medium. The enzyme was efficiently purified by a single-step TALON cobalt affinity chromatography with about 8 fold increase in specific activity, which was determined by a coupled assay with the pyruvate kinase and lactate dehydrogenase. The molecular mass of monomeric UMK was 28.2 kDa and that of the native enzyme was 217 kDa. The enzyme uses UMP as a substrate but not CMP and TMP and activity was enhanced by GTP. Measurements of enzyme kinetics revealed the kcat value of 7.6 +/- 0.4 U mg( 1) or 0.127 +/- 0.006 sec(-1).The protocol reported here can be used for expression of M. tuberculosis UMK in large quantity for formulating a high throughput target-based assay for screening anti-tuberculosis UMK compounds. PMID- 22299416 TI - Effect of BCG vaccination and non-tuberculous Mycobacterium infection on interferon gamma specific assay and a tuberculin skin test among children with a tuberculosis contact in Surabaya, Indonesia. AB - The tuberculin skin test (TST) as a diagnostic tool for tuberculosis (TB) infection is used in many countries, including Indonesia, but lacks specificity. Interferon-gamma is a highly specific assay because it is not influenced by previous BCG vaccination or non-tuberculous mycobacteria (NTM) infections. We aimed to study the effect of BCG vaccination and NTM infection on the results of the interferon-gamma specific assay and TST among children with a TB contact. We carried out a cross-sectional study of children at an outpatient clinic in Surabaya, Indonesia. We studied 37 children aged 1-15 years having a household contact with an acid-fast bacilli positive adult index case. BCG vaccination was determined by the presence of a BCG scar. A PPD RT23 2 tuberculin test was used for the TST. ESAT-6, CFP-10, and TB 7.7(p4) antigens were used for the interferon gamma assay by ELISA. Gastric aspirates were cultured in Lowenstein-Jensen media. A comparison of the two diagnostic tools among children aged 1-5 years without a BCG scar, revealed high agreement, while children with a BCG scar it revealed disagreement. Among children aged > 5 years with or without a BCG scar the comparisons revealed disagreement. Among children aged > 5-10 years, a comparison of the two diagnostic tools among NTM positive and negative children, there was a disagreement in results. Among children aged 1-5 years, the TST was influenced by a BCG scar. Infection with NTM had no influence on the results of the TST among children aged > 5-10 years, while in children aged 1-5 years and > 10 years the results could not be determined in this study. PMID- 22299417 TI - Shock and tuberculous enteritis in a non-HIV infected healthy man. AB - We reported a case of shock, diarrhea and tuberculous enteritis in a previously healthy 32-year-old non-HIV infected man. This case presented initially with acute profuse watery diarrhea. The bacterial and virus cultures were negative. Tuberculous enteritis was diagnosed by detecting Mycobacterium tuberculosis on stool culture 52 days after presentation. The symptoms resolved after treatment with intravenous fluids and corticosteroids but was treated with anti- tuberculous medication. Tuberculous enteritis should be included in the differential diagnosis of patients with enteritis and shock. PMID- 22299418 TI - Widespread presence of dfrA12 and its association with dfrA12-aadA2 cassette in Salmonella enterica isolates from swine. AB - One hundred and eighty-nine Salmonella isolates from swine were tested for susceptibility to nine antimicrobial agents, presence of dfrA12 and class 1 integrons containing dfrA12-orfF-aadA2 cassette. All isolates were multidrug resistant and exhibited highest resistance prevalence to trimethoprim (93%). Most isolates (89%) were intll-positive and 107 isolates (57%) carried dfrA12, all of which were resistant to trimethoprim. Forty-eight dfrA12-harboring strains (45%) were intl1-positive together with dfrA12-aadA2 gene cassette. Fifteen isolates contained dfrA12 but not intl1 and dfrA12-aadA2 cassette. The results indicated a wide distribution of dfrA12 and its role in dissemination of trimethoprim resistance among Salmonella isolates from fattening pigs. PMID- 22299419 TI - Antibiogram and genotyping of Pseudomonas aeruginosa isolated from human, animal, plant, water and soil sources in north India. AB - The present study was designed to determine antibiotic resistance rates and patterns and its correlation with enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) whole genome analysis of Pseudomonas aeruginosa obtained from clinical and environmental sources. In order to determine the possibility of clonality in the bacteria and to track the resistance markers for a better understanding of the epidemiology of drug resistance. A total of 500 strains, 100 each from clinical, water, animal, plant and soil sources were subjected to antibiogram analysis by disc diffusion method. Seventy-five randomly selected strains, 15 each of the five sources were subjected to ERIC-PCR analysis. Clinical isolates were more resistant to combinations of very high numbers of drugs as compared to isolates from other sources. Weak clonality was observed in P. aeruginosa by ERIC-PCR method with 80% of the clinical strains belonging to only 3 clones. It could be concluded that it is the drug selection pressure in clinical environment that is causing the accumulation of drug resistance against many antimicrobials. Furthermore, P. aeruginosa does have clonal expansion. Further studies are warranted to confirm the results. PMID- 22299420 TI - Evaluation of loop-mediated isothermal amplification method for detecting enterotoxin A gene of Staphylococcus aureus in pork. AB - Staphylococcus aureus is an important food-borne pathogen of humans due to ingestion of food containing enterotoxigenic strains. We evaluated the detection of S. aureus enterotoxin A gene (sea) using a loop-mediated isothermal DNA amplification (LAMP) method. Specificity of LAMP method was comparable to that of conventional PCR. Both methods correctly identified sea and did not detect 14 other non-Staphylococcus strains. Limit of detections of LAMP assay for direct detection of S. aureus was 10(4) cfu/ml while that of PCR was 10(3) cfu/ml. Both methods were employed for the detection of S. aureus spiked pork samples to assess their sensitivity. LAMP method was able to detect a minimum of 10(3) cfu/g while PCR 10(4) cfu/g of pork sample following incubation in tryptic soy broth for 6 hours. The LAMP assay allows a one-step identification of gene of interest without any specialized equipment and requires less time than conventional PCR, thus suggesting that the LAMP technique might be an appropriate alternative diagnostic method for detecting enterotoxin A gene of S. aureus in food sample. PMID- 22299421 TI - Prevalence of methicillin-resistant Staphylococcus aureus among university students in Thailand. AB - We studied the prevalence of methicillin sensitive Staphylococcus aureus (MSSA) and methicillin resistant Staphylococcus aureus (MRSA) nasal colonization among healthy young Thai adults. MSSA nasal colonization was found in 30 of 200 subjects (15%). The prevalence of MRSAnasal carriage was 1% (2 of 200) detected by cefoxitin/oxacillin disk diffusion and oxacillin salt screening methods. These carriers were associated with health care risk factors. The two MRSA isolates were mecA positive, SCCmec type II. All S. aureus isolates were tested for antibiotic resistance. Their resistance rates to penicillin, erythromycin, clindamycin, oxacillin and cefoxitin were 96.7, 26.7, 26.7, 6.7 and 6.7%, respectively. All MSSA and MRSA isolates were susceptible to gentamicin, chloramphenicol, trimethoprim/sulfamethoxazole, rifampicin, linezolid, fusidic acid, mupirocin, ciprofloxacin and vancomycin. The results of this first study of MRSA nasal colonization among healthy young Thai adults suggests MRSA is present in the Thai community. PMID- 22299422 TI - Epidemiology of adult candidemia at Chiang Mai University Hospital. AB - A retrospective study was conducted between July 1, 2004 and June 30, 2009 at Chiang Mai University Hospital among 138 patients with candidemia; 85 patients (61.6%) were male and the mean age was 57.7 +/- 19.4 years. Seventy-eight patients (56.5%) had underlying medical conditions. Candida albicans and non albicans Candida were identified in 42 (30.4%) and 96 (69.6%) patients, respectively. Not being admitted to the ICU was the only factor associated with non-albicans candidemia (p = 0.018). Sixty patients (43.5%) had favorable outcomes. Factors independently associated with unfavorable outcomes included patients who were in the ICU (p = 0.025), were intubated (p < 0.001) or were on hemodialysis (p = 0.031); prior abdominal surgery was associated with a favorable outcome (p = 0.026). Candidemia is not a rare condition at this hospital. Early recognition and prompt empirical treatment are essential to improve outcomes of patients at risk for developing candidemia. Improvement of surveillance is crucial to recognizing emergence of highly resistant strains of Candida spp. PMID- 22299423 TI - Decreased retinol transport proteins in Thai post-menopausal women with osteoporosis. AB - High vitamin A ingestion or high serum retinol have been postulated to increase the risk of fractures and osteoporosis by reduced bone mineral density (BMD). Retinol is carried and transported to the tissues bound to retinol binding protein 4 (RBP4) and transthyretin (TTR). The relationships between retinol, retinol transport protein, retinol binding protein 4 (RBP4) and transthyretin (TTR) and BMD and osteoporosis are unclear. To examine the association between retinol and RBP4 and TTR and osteoporosis, 73 osteoporotic and 71 normal Thai postmenopausal women were studied. RBP4 and retinol levels did not differ between the groups. Serum TTR was significantly higher in control than osteoporotic subjects (89.47 and 144.53 microg/ml, respectively, p = 0.003, Mann-Whitney U test). TTR was positively correlated with BMD at several sites, such as the total radius bone (r = 0.172, p = 0.008, Spearman rank test). Osteoporosis risk was analyzed with binary logistic regression. Lean elderly Thais with lower TTR levels had a higher risk of osteoporosis. RBP4 and retinol levels had no relationship with disease status among Thai post-menopausal women. These results suggest calcium, minerals, vitamins and the retinol transport protein, transthyretin may be involved in the pathogenesis of osteoporosis. PMID- 22299424 TI - Urinary and blood cadmium levels in relation to types of food and water intake and smoking status in a Thai population residing in cadmium-contaminated areas in Mae Sot. AB - Human exposure to cadmium (Cd) produces a wide variety of toxic effects involving many organs and systems, but the kidney is the main organ affected among long term Cd-exposed people. In the general population, the primary sources of Cd exposure are cigarette smoke and food (shellfish, offal and certain vegetables). The aims of the study were to investigate the association between urinary and blood Cd levels and personal habits relating to Cd intake (consumption of food stuff, water and tobacco smoking), levels of renal biomarkers in the urine or serum of 314 Thai subjects (85 males, 229 females) who resided in Cd-contaminated areas of Mae Sot District, Tak Province, Thailand. Based on the cut-off levels of 1 microg/g creatinine and 5 microg/l for urinary and blood Cd levels, respectively, nearly all subjects had urinary Cd levels lower than cut-off values for urine and blood (88.2 and 77.7%, respectively). Binary logistic backward stepwise regression analysis with five covariates (gender, residential areas, consumption of bamboo or chicken, and smoking status), and eight covariates (residential areas, consumption of beans, pork, fish or liver, types and sources of rice consumed and smoking status) best predicted urinary and blood Cd levels, respectively. For renal biomarkers, N-acetyl-beta-glucosaminidase (NAG) best predicted both urinary and blood Cd with good accuracy. A larger sample size with equal distribution of subjects with low (< 2 microg/g creatinine) and high (> 2 microg/g creatinine) urinary Cd levels should be studied to obtain the regression equation that would best predict Cd body burden. PMID- 22299425 TI - Illicit cigarette trade in Thailand. AB - The sale and consumption of illicit tobacco increases consumption, impacts public health, reduces tax revenue and provides an argument against tax increases. Thailand has some of the best tobacco control policies in Southeast Asia with one of the highest tobacco tax rates, but illicit trade has the potential to undermine these policies and needs investigating. Two approaches were used to assess illicit trade between 1991 and 2006: method 1, comparison of tobacco used based on tobacco taxes paid and survey data, and method 2, discrepancies between export data from countries exporting tobacco to Thailand and Thai official data regarding imports. A three year average was used to smooth differences due to lags between exports and imports. For 1991-2006, the estimated manufactured cigarette consumption from survey data was considerably lower than sales tax paid, so method 1 did not provide evidence of cigarette tax avoidance. Using method 2 the trade difference between reported imports and exports, indicates 10% of cigarettes consumed in Thailand (242 million packs per year) between 2004 and 2006 were illicit. The loss of revenue amounted to 4,508 million Baht (2002 prices) in the same year, that was 14% of the total cigarette tax revenue. Cigarette excise tax rates had a negative relationship with consumption trends but no relation with the level of illicit trade. There is a need for improved policies against smuggling to combat the rise in illicit tobacco consumption. Regional coordination and implementation of protocols on illicit trade would help reduce incentives for illegal tax avoidance. PMID- 22299426 TI - Association between mandatory seatbelt laws and road traffic injuries in Iran. AB - This study investigated the efficacy of mandatory seatbelt legislation on traffic injuries and intensity of road traffic injuries (RTIs). We carried out a before- after interventional study. Data regarding road traffic accidents and injuries one year before and one and two years after the implementation of mandatory seatbelt legislation were obtained from the traffic police database. Traffic accident mortality was 13.0% of all RTIs during the year prior to implementation. This decreased to 9.7% and 11.4% during the first and second years after implementation, respectively (p < 0.001). The mortality rate was not consistent for seatbelt use since there was a slight increase in the mortality rate in second year after implementation of mandatory seatbelt use although this level was lower than the pre- implementation rate. Our findings suggest mandatory seatbelt use reduces the intensity of RTIs and reduces the crude number of RTIs. PMID- 22299427 TI - Knowledge and practice of travel medicine among primary health care physicians in Qatar. AB - This prospective descriptive survey was conducted among primary health care (PHC) physicians in Qatar from January to May 2007 in order to determine whether travelers obtained correct travel health information. Of 130 physicians approached, 98 agreed to participate in the study and 76 attended the symposium and complete the questionnaire. The questionnaire included sociodemographic characteristics, knowledge and practices about travel medicine before and after the symposium. Forty-four point seven percent of the subjects provided health advice to travelers. Female physicians (59.2%) outnumbered male physicians (40.8%). Qatari physicians (60.5%) outnumbered non-Qataris (39.5%). Most physicians spent at least 15 minutes with each traveler (44.1%). The symposium increased the knowledge of physicians about travel medicine. A significant increase in knowledge was seen in the post-symposium questionnaire for most questions. The main source of knowledge for most physicians was the internet (78.9%). Nearly half the subjects provided pre-travel health advice. All the subjects had improved knowledge of travel medicine following the symposium. PMID- 22299428 TI - An outbreak of angiostrongyliasis in Guanging, People's Republic of China: migrants vulnerable to an emerging disease. AB - Angiostrongyliasis has been frequently reported from the People's Republic of China during the last decade. An outbreak of angiostrongyliasis among migrant laborers in Guangning, Guangdong Province is described here. A questionnaire was developed to collect epidemiological and clinical information about 17 migrant laborers from the Bai ethnic group in Dali, Yunnan Province. Serum samples were collected and tested by enzyme-linked immunosorbent assay. Rats and mollusks from the same area where patients had collected Pomacea canaliculata were examined for presence of Angiostrongylus cantonensis. All 17 Bai migrant laborers consumed P. canaliculata and six had meningitis 3-19 days after consumption of P. canaliculata. Headache, myalgia and fatigue were the most common symptoms. Blood samples from 5 patients were positive for antibodies to A. cantonensis. The places where the migrant laborers collected P. canaliculata were identified as endemic areas for A. cantonensis. This outbreak highlights the vulnerability of migrants to angiostrongyliasis. PMID- 22299429 TI - The impact of a national program to eliminate lymphatic filariasis in selected Myanmar immigrant communities in Bangkok and Ranong Province, Thailand. AB - Some immigrants from Myanmar to Thailand have brought Wuchereria bancrofti infections with them, causing a community health problem for Thai citizens. The seroprevalence of bancroftian filariasis was detected in 438 and 512 Myanmar immigrants residing in Bangkok and Ranong Provinces, respectively, along with 81 Thai citizens living in Bangkok. The immunochromatograpy card test was positive in 5 Myanmar immigrants living in Bangkok and 1 living in Ranong for a prevalence of 0.63%. Antifilarial IgG4 antibodies were found in 21 Myanmar immigrants living in Bangkok and 14 living in Ranong for a prevalence of 3.68%. None of the samples from Thai citizens were positive with either test. These prevalence rates are lower than those observed between 2001 and 2005. The Thai mass drug administration program to eliminate lymphatic filariasis among Myanmar immigrants appears to be a successful public health strategy. PMID- 22299430 TI - Abnormal Taenia saginata tapeworms in Thailand. AB - Sixty-eight residents of Ban Luang and Ban Pang Kae villages, in Nan Province, northern Thailand, visited our mobile field station in September 2006 and March 2007, seeking treatment for taeniasis. After treatment, 22 cases discharged tapeworm strobila in their fecal samples and 17 scolices were recovered. Among these, 3 were morphologically abnormal, with six suckers on the scolex. To confirm the species of these tapeworms, the mitochondrial cytochrome c oxidase subunit I (COI) gene was used as a molecular marker. The partial COI sequences (800 bp) of the abnormal tapeworms were identical to the sequences of Taenia saginata deposited in Genbank. PMID- 22299431 TI - Laryngeal sarcocystosis accompanying laryngeal squamous cell carcinoma: case report and literature review. AB - Laryngeal sarcocystosis is an uncommon zoonotic coccidian protozoal infestation of human beings. The authors reviewed the pathology of 1,063 laryngeal biopsies over the past 10 years (2000 to 2009). Only one case of laryngeal sarcocystosis accompanying laryngeal squamous cell carcinoma was identified. The overall prevalence of laryngeal sarcocystosis was 0.094%. The case was a 66-year-old man who presented with voice hoarseness for six months. Physical examination and computed tomography revealed an ulcerative exophytic mass on the right true vocal cord, suggestive of laryngeal carcinoma. He underwent a right frontolateral partial laryngectomy. Histopathology showed a nonkeratinizing squamous cell carcinoma with Sarcocystis spp in the vocalis muscle. He was followed up and enrolled in speech therapy. The authors briefly review the clinicopathologic features and pathogenesis of muscular sarcocystosis and concurrent laryngeal sarcocystosis and squamous cell carcinoma. PMID- 22299432 TI - Characteristics of Aedes (Stegomyia) albopictus Skuse (Diptera:Culicidae) breeding sites. AB - We investigated the physicochemical characteristics of Aedes albopictus Skuse viz. breeding sites, by examining coconut shells, tires and plastic containers in a chikungunya affected area of Calicut, India. The study design was a cross sectional ecological type. Thirty-four water samples were collected randomly from coconut shells, tires and plastic containers. The larvae were counted and the water was examined. The mean number of larvae per 500 ml was significantly higher in coconut shells than in tires and plastic containers. A negative correlation was observed with pH and a positive correlation was seen with most other variables. Coconut shells were the preferred breeding site for Ae. albopictus mosquitoes in our study. The rich organic content, low illumination and small orifice of the coconut shells could be the reasons for this. The higher salinity of the coconut shells did not affect breeding or survival. PMID- 22299433 TI - Efficacy of herbal essential oils as insecticide against Aedes aegypti (Linn.), Culex quinquefasciatus (Say) and Anopheles dirus (Peyton and Harrison). AB - The essential oils of Cananga odorata (ylang ylang), Citrus sinensis (orange), Cymbopogon citratus (lemongrass), Cymbopogon nardus (citronella grass), Eucalyptus citriodora (eucalyptus), Ocimum basilicum (sweet basil) and Syzygium aromaticum (clove), were tested for their insecticide activity against Aedes aegypti, Culex quinquefasciatus and Anopheles dirus using the WHO standard susceptibility test. These were applied in soybean oil at dose of 1%, 5% and 10% (w/v). C. citratus had the KT, values against the three mosquito species tested but the knockdown rates (at 10, 30 and 60 minutes) were lower than some essential oils. C. citratus oil had high insecticidal activity against Ae. aegypti, Cx. quinquefasciatus and An. dirus, with LC50 values of < 0.1, 2.22 and < 0.1%, respectively. Ten percent C. citratus gave the highest mortality rates (100%) 24 hours after application. This study demonstrates the potential for the essential oil of C. citratus to be used as an insecticide against 3 species of mosquitoes. PMID- 22299434 TI - Early reporting of pandemic flu and the challenge of global surveillance: a lesson for Southeast Asia. AB - Abstract. An important issue at the start of the H1N1/2009 pandemic is global reporting of pandemic cases. Reports during the first few weeks of the pandemic showed spread of the disease from Mexico to many countries, but few cases were reported from low and middle income countries. Analysis of the data of international passengers departing from Mexican airports early in the H1N1/2009 outbreak shows a strong association between the number of passengers and reports of confirmed cases. In developing countries first case detection was slower and the chance of reporting the influenza cases after controlling for air traveller intensity was significantly lower. Delays in detection and reporting can jeopardize the success of a global response to a pandemic. A number of implications can be drawn from this, including the need to strengthen health system surveillance capacities in developing countries in Southeast Asia and globally for a better regional and global response. PMID- 22299435 TI - Evaluation of respiratory findings in Crimean-Congo hemorrhagic fever. AB - Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease with a high mortality rate causing viral hemorrhagic fever. We studies the respiratory system findings, demographics, clinical and laboratory findings of patients with CCHF admitted to our hospital. In this retrospective study we evaluated 108 patients with CCHF confirmed by laboratory findings. The charts of all hospitalized patients were reviewed, and the age, sex, occupation, city of residence, history of tick bite or of removing a tick, smoking history, chest X-ray results, outcome and clinical and laboratory findings were recorded for each patient. Sixty of the chest radiographs were read as normal, 33 were read as showing unilateral pathology and 15 showed bilateral pathology. Seven of the 108 patients died due to severe pulmonary infection and hemorrhage. The frequency of pathological chest radiographs was higher among the CCHF patients who died than among the survivors, but the difference was not significant. Pulmonary parenchyma hemorrhage can occur in CCHF patients with hemoptysis, dyspnea, chest pain and infiltration on chest radiographs and may lead to morality. PMID- 22299436 TI - Infection-associated hemophagocytic syndrome among patients with dengue shock syndrome and invasive aspergillosis: a case series and review of the literature. AB - The authors report four autopsy cases of previously healthy children with dengue shock syndrome complicated with infection-associated hemophagocytosis and invasive aspergillosis. Hemophagocytosis is confirmed by histopathology of autopsied reticuloendothelial organs. All four children were identified to have invasive aspergillosis by histopathology and three cases were positive on fungal culture for Aspergillus spp. Regarding the cause of death among the four children without pre-existing underlying disease, three cases were directly ascribable to invasive aspergillosis and the remaining case was ascribed to dengue shock syndrome. The transmigration of preexisting fungi from the respiratory mucosa damaged by the dengue shock process is postulated as the pathogenesis of invasive aspergillosis. The main predisposing factor was found to be prolonged dengue shock syndrome. We reviewed the clinicopathologic features and therapeutic management of infection-associated hemophagocytic syndrome in patients with dengue shock syndrome and invasive aspergillosis. PMID- 22299437 TI - E4 expression of human papillomavirus in cervical samples with different cytology categories. AB - In some circumstances, infection with human papillomavirus (HPV), especially HPV type 16 (HPV16), progresses to cervical cancer. Viral E4 expression reflects viral replication and translation and its presence may rule out a latent infectious stage. Twenty cervical cytology samples with known HPV 16 infection of each cytological category namely, negative for intraepithelial lesion (NIL), low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL) and squamous carcinoma (SCC) were investigated by single-step quantitative RT PCR for HPV 16 E4 mRNA, which was not found in any NIL sample but in all LSIL and HSIL samples. Thus, E4 expression assay should be useful for determining precancerous states and may be suitable as an adjunct in cervical HPV testing. PMID- 22299438 TI - Stigmatization and discrimination towards people living with or affected by HIV/AIDS by the general public in Malaysia. AB - Globally, HIV/AIDS-related stigma and discriminatory attitudes deter the effectiveness of HIV prevention and care programs. This study investigated the general public's perceptions about HIV/AIDS-related stigma and discrimination towards people living with or affected by HIV/AIDS in order to understand the root of HIV/AIDS-related stigma and discriminatory attitudes. Study was carried out using qualitative focus group discussions (FGD). An interview guide with semi structured questions was used. Participants were members of the public in Malaysia. Purposive sampling was adopted for recruitment of participants. A total 14 focus group discussions (n = 74) was carried out between March and July 2008. HIV/AIDS-related stigma and discrimination towards people living with HIV/AIDS (PLWHA) was profound. Key factors affecting discriminatory attitudes included high-risk taking behavior, individuals related to stigmatized identities, sources of HIV infection, stage of the disease, and relationship with an infected person. Other factors that influence attitudes toward PLWHA include ethnicity and urban rural locality. Malay participants were less likely than other ethnic groups to perceive no stigmatization if their spouses were HIV positive. HIV/AIDS-related stigma and discrimination were stronger among participants in rural settings. The differences indicate attitudes toward PLWHA are influenced by cultural differences. PMID- 22299439 TI - Accelerating the development of an AIDS vaccine: the AIDS vaccine for Asia Network (Avan). AB - HIV/AIDS is a major public health problem worldwide, especially in developing countries. The development of a safe and effective HIV vaccine is central to stopping the epidemic and would be a great public health tool. The AIDS Vaccine for Asia Network (AVAN) is a group of concerned investigators committed to assisting regional and global HIV vaccine efforts. AVAN's focus on improving the coordination and harmonization of research, ethical reviews, clinical trial capacity, regulatory frameworks, vaccine manufacturing, community participation, and government advocacy could help accelerate HIV vaccine efforts in the region. At a meeting in November 2010, researchers from various countries in Asia presented their progress in HIV vaccine research and development. Six working groups discussed the current status, gaps and methods to strengthen capacity and infrastructure in various areas related to AIDS vaccine research and development. These discussions led to the development of prioritized action plans for the next 5 years. This report describes the gaps and challenges HIV vaccine research faces in the region and recommends improvement and standardization of facilities, and coordination and harmonization of all activities related to AIDS vaccine research and development, including possible technology transfer when a vaccine becomes available. PMID- 22299440 TI - TB-SA antibody test for diagnosis and monitoring treatment outcome of sputum smear negative pulmonary tuberculosis patients. AB - The objectives of this study were to evaluate the suitability of the TB-SA antibody test to diagnose tuberculosis in sputum smear negative (SS-) pulmonary tuberculosis (TB) patients and its applicability for monitoring treatment outcomes in these patients. This study was conducted in three counties/districts in Chongqing Municipality, Liaoning Province, China between June 2005 and June 2007. A total of 432 SS suspected pulmonary TB patients were recruited and their blood was collected prior to treatment, at the end of 1 month of treatment, 2 months of treatment and 6 months of treatment (E6MT). The serum samples were analyzed with a TB-SA antibody test kit. Of the 432 SS suspected pulmonary TB patients, serum samples were obtained at all time points in 316 patients and analyzed. The 316 patients were divided into three groups according to sputum smear and sputum culture results and the chest X-ray results before treatment and at E6MT. Ten point four percent were SS-/culture positive (C+), 73.1% were SS /culture negative (C-) with X-rays abnormalities, and 16.5% were SS-/C- without X rays abnormalities. The positive rates for TB-SA antibody in the three groups were 57.6, 44.6 and 44.2%, respectively, before treatment, and 18.2, 19.1 and 26.9%, respectively, at E6MT. There was a significant decrease in TB-SA antibody positivity with treatment for all 3 groups. The TB-SA antibody test may be a useful adjunct to diagnose tuberculosis in SS- pulmonary TB patients, and may be useful for monitoring treatment outcomes of SS- pulmonary TB patients. PMID- 22299441 TI - Drug susceptibility patterns of Mycobacterium tuberculosis and clinical outcomes of drug-resistant tuberculosis at Srinagarind Hospital, a tertiary care center in northeastern Thailand. AB - Drug-resistant tuberculosis is a major public health problem. The aim of this study was to assess the local susceptibility patterns of Mycobacterium tuberculosis and clinical outcomes of drug resistant tuberculosis (DR-TB) at Srinagarind Hospital, a tertiary care center in northeastern Thailand. Between January 2004 and December 2008, 1,052 patients had culture-proven M. tuberculosis infections at Srinagarind Hospital. M. tuberculosis was resistant to isoniazid (2.3%), rifampicin (2.8%), ethambutol (3.8%), streptomycin (2.1%), kanamycin (0.7%) and ofloxacin (1.9%). The occurrences of multi-drug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) were 1.2% and 0.38%, respectively. Of the 65 DR-TB patients, complete medical records were found for 55. The male to female ratio was 2.2:1. The mean age was 50 years. Thirteen patients had MDR-TB. The duration of symptoms in the MDR-TB group was longer than the non-MDR-TB group, 11.6 months vs 2.6 months, respectively. Half of MDR-TB and one-third of non-MDR-TB patients had a previous history of being treated for tuberculosis. Nearly 20% of cases were HIV positive. Mono-drug resistance was initially treated with standard first-line drugs (CAT 1). The clinical course was more likely to be worse during the maintenance phase if there was resistance to rifampicin. Whenever there was resistance to two, three or four drugs, the antituberculosis drugs were prescribed based on susceptibility patterns. Only 30% of patients with MDR-TB and XDR-TB responded to treatment. Culture and sensitivity testing for M. tuberculosis cases is recommended in patients at high risk for DR-TB, such as patients previously treated for tuberculosis and those HIV positive. PMID- 22299442 TI - gyrA and gyrB mutations in ofloxacin-resistant Mycobacterium tuberculosis clinical isolates in Thailand. AB - In order to identify mutations in gyrA and gyrB genes in 92 ofloxacin-resistant Mycobacterium tuberculosis (OFXr-MTB) clinical isolates collected from Siriraj Hospital, Mahidol University and Chest Disease Institute, Thailand. The quinolone resistance-determining regions (QRDR) of gyrA and gyrB in all 92 OFXr-MTB isolates were amplified using polymerase chain reaction and sequenced. There were 70 isolates with point mutations associated with ofloxacin resistance. In gyrA QRDR, 69 isolates had mutations in gyrA Gly88 (Ala/(75), Ala90 (Val), Ser91 (Pro) and Asp94 (Gly/Ala/His/Asn), the latter being the most common (42%). Only one isolate was found with mutation at position Asp495 (Asn). The other 22 isolates had no mutations in both gyrA and gyrB QRDR. Thus, point mutations in gyrA and gyrB QRDR were responsible for OFXr-MTB clinical isolates in Thailand. PMID- 22299443 TI - Surface plasmon resonance immunosensor for rapid and specific diagnosis of melioidosis antibody. AB - Melioidosis, caused by Burkholderia pseudomallei, is a potentially fatal disease, which requires an accurate and rapid diagnosis. This paper reports on the highly sensitive and specific detection of melioidosis antibodies by surface plasmon resonance immunosensor. The sensing surface was immobilized with B. pseudomallei BipD protein via a 11-mercaptoundecanoic acid self-assembled monolayer. Under optimum conditions individual sera of melioidosis patients, non-melioidosis patients (negative) and blood donors (control) were analyzed at a dilution of 1:6,000 in 10 mM phosphate buffered saline pH 7.50. The cut-off value determined from the mean +/- 2SD of 20 control and 20 negative sera was 3.3 m degrees. At this cut-off both sensitivity and specificity were 100%. The system required only a short analysis (20 minutes) and regeneration time (12 minutes). In addition, one immobilization of the sensing surface could be reused more than 30 times. The advantages of the proposed method are savings in both time and cost of analysis, while at the same time providing excellent sensitivity and specificity. PMID- 22299444 TI - Genotypic and phenotypic differentiation of Salmonella enterica serovar Paratyphi B in Malaysia. AB - Abstract. Salmonella enterica serovar Paratyphi B is known to cause either paratyphoid fever or gastroenteritis. Differentiation of Salmonella ser. Paratyphi B into biotype Java (d-tartrate fermenting, dT+) and biotype Paratyphi B (d-tartrate non-fermenting, dT) is important for Salmonella epidemiology. This study applied a PCR approach to differentiate the two biotypes to augment the conventional biochemical method and to determine the antibiograms and genomic diversity of Malaysian S. Paratyphi B. Among 100 strains tested (clinical, 86; non-humans, 14), only two clinical strains were confirmed as biotype Paratyphi B as indicated by both lead acetate test and PCR. Antibiotic resistance rates were as follows: streptomycin 18%, sulphonamides 13%, ampicillin 10%, chloramphenicol 4%, tetracycline 3%, cefotaxime 2%, cefpodoxime 2%, ceftazidime 2%, gentamicin 1% and trimethoprim 1%. None showed resistance towards amoxicillin-clavulanic acid, ceftiofur, ciprofloxacin, nalidixic acid and trimethoprim-sulphamethoxazole. Seven strains showed multidrug resistance towards 3 or more classes of antimicrobial agents. REP-PCR and PFGE generated 32 and 76 different profiles, respectively. PFGE (D = 0.99) was more discriminative than REP-PCR (D = 0.93) and antimicrobial susceptibility test (D = 0.48) in subtyping the strains. Strains isolated 18 years apart (1982 - 2008) from different localities in Malaysia were clonally related as demonstrated by REP-PCR and PFGE, indicating that these strains were stable and widely distributed. In some clusters, strains isolated from different sources (clinical, food and animal) were grouped together. Thus, biotype Java was the most common biotype of Salmonella ser. Paratyphi B in Malaysia. The PCR approach is highly recommended due to its simplicity, specificity and ease of operation. The level of antimicrobial resistance among Salmonella ser. Paratyphi B remained relatively low in Malaysia but the emergence of resistance to cephalosporins is a cause for concern. PMID- 22299445 TI - Heterologously type IV pilus expressed protein of Burkholderia pseudomallei is immunogenic but fails to induce protective immunity in mice. AB - Burkholderia pseudomallei is the causative agent of melioidosis, a severe disease of humans and animals. At present, no effective vaccine against melioidosis exists. Bacterial type IV pilin proteins have been used successfully as subunit vaccines. In this study, we evaluated a heterologously expressed and purified type IV pilus protein (PilV) of B. pseudomallei strain K96243 as a candidate subunit vaccine. PilV protein was assessed for its ability to protect BALB/c mice against B. pseudomallei strain G207 infection. Mice subcutaneously immunized with purified PilV protein produced high titers of IgG antibodies, which were strongly biased towards IgG1, with lower levels of IgG2a. Even though the PilV protein was highly immunogenic, it could not induce protection against a lethal B. pseudomallei challenge. Possible mechanisms of this non-protection phenomenon are discussed. PMID- 22299446 TI - Impaired interleukin-1beta expression by monocytes stimulated with Staphylococcus aureus in diabetes. AB - Diabetic patients with poorly controlled blood glucose have frequent and persistent bacterial infections particularly those infecting the skin, such as Staphylococcus aureus and S. epidermidis. The function of phagocytes of diabetic patients is believed to be impaired due to hyperglycemia, leading to suboptimal immune response to clear acute infection. The present study investigated interleukin (IL)-1beta expression by diabetic patients' monocytes (n = 22) experimentally infected with S. aureus compared with that from healthy subjects (n = 30). In addition, the in vitro effect of hyperglycemia on IL-1beta expression by monocytes from normal subjects (n = 18) stimulated with S. aureus and S. epidermidis was investigated. Monocytes from diabetic patients, stimulated or not with S. aureus, express significantly lower levels of IL-1beta than those from healthy subjects. In vitro hyperglycemia did not affect IL-1beta expression by unstimulated monocytes. However, at the same levels of glucose normal monocytes stimulated with S. aureus produce significantly higher IL-1beta than those stimulated with S. epidermidis. These findings suggest that diabetic patients have abnormally lower IL-1beta expression and hyperglycemia is related to abnormal expression of IL-1beta by monocytes, which could lead to enhanced susceptibility to infection by the more virulent bacteria. PMID- 22299447 TI - High anemia prevalence in western China. AB - We assessed the prevalence of anemia among schoolchildren in western China as determined by seven cross-sectional surveys involving 12,768 children aged 8-12 years. Subjects were selected randomly from 283 primary schools in 41 economically disadvantaged counties of Ningxia, Qinghai, Shaanxi and Sichuan Provinces. Data were collected through questionnaires and hemoglobin levels were measured. The anemia prevalence was 34% using the WHO hemoglobin cutoff of < 120 g/l. Boarding students and girls were more likely to be anemic. The prevalence of anemia in schoolchildren was high. Iron deficiency is a significant nutrition issue in China. PMID- 22299448 TI - Higher intake of fruits and vegetables in pregnancy is associated with birth size. AB - Maternal nutrition has a programming effect on fetal growth. This cross-sectional study investigated the association between maternal micronutrient, fruit and vegetable intake with birth size. Nutrient and food intake were examined using a validated semi-quantitative food frequency questionnaire. One hundred twenty-one pregnant women at 28 to 38 weeks gestation aged 19-40 years, were recruited from the Universiti Sains Malaysia Hospital, Malaysia. Birth weight, length and head circumference were obtained from the medical records. Data were analyzed using multiple linear regression. Results indicate no significant association between any of the measured micronutrients and birth size. However, 2 of the 6 vegetable subgroups and those consumed fruit during pregnancy had children whose birth size was significantly associated with consumption. An increase of 10 g of leafy vegetables per day was associated with a 1.78 cm increase in head circumference (p = 0.04), and tuber vegetable intake was associated with birth length (beta = 0.21, p = 0.03) and head circumference (beta = 0.21, p = 0.01). Fruit intake was associated with birth weight (beta = 0.19, p = 0.04), birth length (beta = 0.20, p = 0.04) and head circumference (beta = 0.19, p = 0.03). The lack of association between maternal nutrient intake and fetal growth and the significant association between fruit and vegetable intake and birth size suggests the existence of other micronutrients and phytochemicals present in foods that play an important role in birth size. The types of nutrients and their roles in birth size warrant further investigation. PMID- 22299449 TI - Multicenter validation of fully automated capillary electrophoresis method for diagnosis of thalassemias and hemoglobinopathies in Thailand. AB - Thalassemias and hemoglobinopathies are highly prevalent in Thailand and other Southeast Asian countries. Accurate and precise separation of hemoglobin types, together with reliable quantitation, are essential for differential diagnosis of these diseases. Presented in this study is a multicenter validation of a fully automated capillary electrophoresis (CE) method for hemoglobin separation and quantitation involving four reference laboratories in Thailand. Analytical performance characteristics, including precision and accuracy were compared with existing validated HPLC and LPLC methods using 412 blood samples from unrelated subjects. Coefficient of variance of Hb A2 quantitation was 1.80-2.86, 1.26-5.13 and 1.08-6.66% for within run, between run and interlaboratory comparison, respectively. Results of Hb A2 and Hb F quantitated by the CE method correlates well with those of the two comparative methods (r = 0.98-0.99). The CE method correctly determined the genotypes (thalassemias and hemoglobin variants) of all blood samples tested. The major advantage of the CE system is its ability to separate and quantitate Hb A2, Hb E, Hb F, Hb H and Hb Bart's, which are important parameters required for diagnosis of thalassemias and hemoglobinopathies. PMID- 22299450 TI - Craniofacial deformities in transfusion-dependent thalassemia patients in Malaysia: prevalence and effect of treatment. AB - This comparative cross-sectional study was conducted in the pediatric daycare unit, Hospital Universiti Sains Malaysia to determine the prevalence of craniofacial deformities (CFD) and the association between these deformities and different clinical presentations among thalassemia patients. Patients were classified as either craniofacial deformity positive (CFD+) or craniofacial deformity negative (CFD-) by two examiners based on the presence or absence of deformity of the cheeks, frontal and/or maxillary bones. Fifteen clinical parameters were compared between the groups. Nineteen out of 43 patients (44.2%; confidence interval, 30.2-58.2%) had craniofacial deformities (CFD+). Both groups were comparable among the clinical parameters studied. Patients in the CFD+ group did not start their blood transfusions significantly earlier than the CFD- group (p = 0.50) and had a nonsignificantly lower mean pretransfusion hemoglobin level than the CFD- group (p = 0.71). Patients receiving regular monthly blood transfusions had a nonsignificantly smaller percentage of CFD than those transfused less often (p = 0.495). CFD+ patients had a splenectomy at a nonsignificantly younger age than CFD- patients (p = 0.36). HbE/beta thalassemia patients were not significantly less likely to develop CFD than other varieties (p = 0.50) and males had a nonsignificantly higher percentage of CFD than females (p = 0.29). This study shows CFD in thalassemia patients are still prevalent but no significant associated factors were found; however, a nonsignificantly higher prevalence of CFD was observed in patients with signs of severe disease and less efficient treatment. PMID- 22299451 TI - Association between hypertension and stroke among young Thai adults in Bangkok, Thailand. AB - A hospital based case-control study was conducted to assess the association between hypertension and stroke among young Thai adults at a private hospital in Bangkok, Thailand. The study population was comprised of 98 inpatients with a first diagnosis of stroke and 98 inpatients without stroke admitted from 2006 to 2008, aged 18-45 years. Cases were matched with controls by sex and five year age group intervals. Risk factors for stroke, including hypertension were collected using a questionnaire. Significant finding on physical examination and blood testing were obtained from the patients' charts. Multivariate analysis revealed significant risk factors for stroke were: diagnosis of hypertension (adjusted OR 8.94; 95% CI 1.47-54.34), family history of stroke (adjusted OR 16.15; 95% CI 1.71-151.82), history of no or irregular exercise (adjusted OR 8.06; 95% CI 1.12 57.60) and having a low high density lipoprotein level (adjusted OR 5.93; 95% CI 1.11-31.52). Hypertension was the greatest risk factor for stroke among young Thai adults. Modification of lifestyle to reduce risk for stroke should focus on exercise, regular health check-ups and adequate treatment of hypertension. PMID- 22299452 TI - Factors related to tobacco use among middle school students in China. AB - The objectives of this study were to determine the status of tobacco use among middle school students in China, and to identify factors related to tobacco use. The study was conducted in December 2009. An ecological model was used to formulate the conceptual framework of the study. Three thousand two hundred twenty-one middle school students aged 12-17 years were selected by three stage stratified cluster sampling. Data were collected by self-completed questionnaires and interviews. The prevalence of current smoking was 10.6%; 16.2% among males and 4.3% among females. The prevalence of ever having smoked was 19.7%, 25.3% among males and 13.4% among females. Zero point seven percent of middle school students used other forms of smoked tobacco products other than cigarettes. Multinomial logistical regression analysis found gender, age, knowledge, attitude, life skills, self-concept, parental smoking, friends smoking, friends attitudes toward smoking, peer pressure, family rules, availability of cigarettes, tobacco-free school environment, smoking intervention program, community tobacco control activities, and tobacco control policies had significant associations with smoking behavior. Structural equation modeling (SEM) analysis found intrapersonal factors had direct relationships with smoking behavior among smoking middle school students. Interpersonal factors, organizational factors and policies had indirect relationships with smoking behavior, and through intrapersonal factors affected smoker behavior among middle school smoking students. PMID- 22299453 TI - Participatory capacity building in occupational disease surveillance among primary care unit (pcu) health personnel. AB - This study aimed to demonstrate participatory capacity building regarding occupational disease surveillance (ODS) could enable the Primary Care Unit (PCU) health personnel provide satisfactory occupational health services for workers in the community. A needs assessment was carried out to identify gaps in PCU health personnel skills and knowledge so these areas could be strengthened. An ODS training program was developed. Fifty-nine health personnel participated in a 5 day workshop and received instructions regarding a wide range of occupational diseases, surveillance methods, prevention measures, and Ministry of Public Health (MOPH) surveillance systems. Participants self reported positive changes in knowledge and skills, as well as a high level of satisfaction with the workshop. However, many participants noted barriers to consistently implementing reporting procedures. PMID- 22299454 TI - Determinants of monthly reporting by village health volunteers in a poor rural district of Lao PDR. AB - Village health volunteers (VHV) are community members trained as lay health workers. They are engaged in a variety of health care programs in which they are often required to make regular reports to their supervisors, including community based surveillance data. The objective of this study was to identify factors influencing monthly reporting activities among VHV in a remote area of Lao PDR. Data were collected through structured interviews with VHV in November 2008. Logistic regression analysis was conducted to assess associations between completion of monthly reporting and socio-demographic and economic factors and VHV-related factors, such as training, experience, type of main job, and satisfaction with incentives. Of the 137 VHVs from 97 villages interviewed, 39.4% stated they submitted their monthly report at least once over the past three months. Most frequently mentioned reasons for not reporting were "no money to visit health center", "no time to visit health center", and the "health center is located too far". Logistic regression analysis showed failure to report was associated with longer distances between the VHV village and the responsible health center, lower levels of education, fewer training sessions attended by the VHV, and the type of main job of the VHV. Although most VHVs owned vehicles and were given financial support for travel, difficulty traveling to the responsible health center remains the leading cause for failure to report. PMID- 22299455 TI - Comparison of quality of life and mental health among elderly people in rural and suburban areas, Thailand. AB - This community based cross-sectional study design assessed the quality of life, mental and physical health among people aged > or = 60 years living in rural and suburban areas of northern Thailand. A cluster random sampling technique was used. The instruments used to assess quality of life were the Thai General Health Questionnaire (Thai-28), the WHO Quality of Life Assessment in Thai (WHOQOL-BREF THAI), and a history and physical examination. The validity and reliability of the 2 written instruments (Thai-28 and WHOQOL-BREF-THAI) were detected and the Cronbach's alpha coefficient was 0.84 for the WHOQOL-BREF-THAI, and 0.94 for the Thai GHQ-28. The face-to face interview were conducted by trained interviewers. A chi-square test was used to determine significant differences at alpha = 0.05. Two hundred forty-seven subjects were recruited into the study, of which 225 were used for analysis. Forty-eight point five percent and 51.5% of subjects were from rural and semi-urban areas, respectively. Forty-five point three percent were males; the main age group was 70-79 years old (46.5%). The subjects from suburban areas had a higher quality of life in aspect to physical health (p = 0.011), mental health (p = 0.025), and social relationships (p = 0.012). Social relationships among females from difference areas were significantly different (p = 0.01). Subjects from rural areas had better mental health than those from suburban (p = 0.0001). Living in a suburban area had both positive and negative associations with quality of life that need to be further clarified to develop an elderly health care model for the community. PMID- 22299456 TI - Effect of five different dental products on surface hardness of enamel exposed to chlorinated water in vitro. AB - The objective of this study was to assess the effect of five different dental products on surface microhardness of enamel exposed to chlorinated water in vitro. Sixty human sound premolar teeth, extracted for orthodontic reasons, were used and randomly divided into 6 groups (10 specimens each group: artificial saliva, 1,000 ppm fluoride toothpaste, CPP-ACP paste, CPP-ACP with 900 ppm fluoride paste, CPP toothpaste and tricalcium phosphate with 950 ppm fluoride paste. All specimens were immersed in chlorinated water at pH 5 for 24 hours and then remineralized by coating with a dental product from each group for 5 minutes and kept in artificial saliva at 37 degrees C for 6 hours. The surface microhardness of the enamel was measured with a Vickers hardness tester at baseline, after erosion by chlorinated water and after remineralization. Comparisons of the mean microhardness within each group were made a one-way repeated measures ANOVA and between groups using a one-way ANOVA and an LSD test at p < 0.05. The mean surface microhardness in all groups decreased significantly after eroding with chlorinated water and increased after remineralization. After remineralization, the mean surface microhardness of the artificial saliva group was significantly less than the other groups. Five different dental products (1,000 ppm fluoride toothpaste, CPP-ACP paste, CPP-ACP with 900 ppm fluoride paste, CPP toothpaste and tricalcium phosphate with 950 ppm fluoride paste) increased the hardness in vitro of eroded enamel caused by chlorinated water. PMID- 22299457 TI - Efficacy of mefloquine treatment and genetic profiles in uncomplicated Plasmodium falciparum malaria in southern Lao PDR. AB - We conducted a 28-day follow-up of 17 Laotian patients diagnosed with uncomplicated Plasmodium falciparum malaria treated with mefloquine (Mephaquine, MQ) alone to determine the efficacy. All patients were completely cured with MQ, without reappearance of asexual stage parasitemia at follow-up. Of the 7 isolates tested for genotypic analysis, one isolate was a Y86 mutant type of the pfmdr1 gene, the others were N86 wild. These findings suggest no MQ resistance in the study area possibly because the drug is rarely used in southern Lao PDR. PMID- 22299458 TI - Determination of discriminatory power of genetic markers used for genotyping Giardia duodenalis. AB - Small subunit ribosomal DNA (SSU-rDNA), glutamate dehydrogenase (gdh), beta giardin, triosephosphate isomerase (tpi), and elongation factor 1-alpha (ef1 alpha) genes are useful genetic markers for genotypic analysis of the intestinal protozoan, Giardia duodenalis (syn. G. lamblia, G. intestinalis), the cause of enteric disease in humans. To quantitatively compare the discriminatory power of these loci, 43 fecal samples were collected from central, northern and eastern Thailand and G. duodenalis specimens were analyzed using PCR-based genotyping and subcloning methods. Approximately equal prevalence of assemblage A (21) and B (22) were present among these populations. Analysis of Simpson's index and Wallace coefficient values from assemblage B isolates together with the data obtained from GenBank showed that the combination of two loci provides a higher discrimination power for subgenotyping G. duodenalis than using any single locus. PMID- 22299459 TI - Roles of partially purified antigens from Gnathostoma spinigerum larvae on antibody production by human B cell culture. AB - A 24 kDa protein from advanced third stage Gnathostoma spinigerum larvae (GsAL3) is used for gnathostomiasis serodiagnosis. This study investigated whether partially purified protein antigen (Ag) from GsAL3 (Gnath Ag), prepared by simple gel filtration chromatography, could be used for serodiagnosis. Using DNA microarray analysis, significant gene expression related to immunoreactivity was examined in peripheral blood mononuclear cells (PBMC) cocultured with Gnath Ag. Antigenicity was then determined by its capacity to induce antibody production among purified naive B cells stimulated with Gnath Ag and anti-CD40. Seven and 14 days post-exposure, immunoglobulin levels (Igs) in culture supernatants were determined by enzyme-linked immunosorbent assay. The Gnath Ag stimulated PBMC had a significant increase in gene expression related to an innate immune response and decreased cell mediated immunity, but the expression of gene related antibody production was not markedly increased. The Gnath Ag stimulated naive B cells or lipopolysaccharide primed B cells to produce low levels of specific antibody. Our findings support the assertion that partially purified Gnath Ag possess low antigenicity for Ig induction. Further studies are needed to improve G. spinigerum larva Ag for serodiagnosis. PMID- 22299460 TI - Impact of hookworm deworming on anemia and nutritional status among children in Thailand. AB - Hookworm infection is associated with anemia, especially among children and deworming can improve anemic status; however, little information is available about the degree to which anemia improves after deworming. We chose hookworm endemic rural areas of Thailand, Nan Province in the north, Kanchanaburi Province in the west and Nakhon Si Thammarat Province in the south, to evaluate this problem. Subjects were selected by primary school-based stool egg examinations. Blood tests of 182 hookworm-positive primary school children, composed of 22 heavy, 65 moderate and 95 light infections, were compared with a control group of 57 children who were helminth-free both before and after receiving deworming medicine. Before deworming, the red blood cell (RBC), hemoglobin (Hb), hematocrit (Hct), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) and albumin levels of the hookworm-infected groups were significantly lower than the helminth-free control group. The Hb and Hct levels showed an inverse relationship with intensity of hookworm infection. After deworming, the Hb, Hct, total protein and albumin levels of the hookworm-infected children improved within 2 months to become comparable with the helminth-free control group. One year after deworming, the mean blood test results in the 2 groups were not significantly different from each other. PMID- 22299461 TI - Taeniasis/cysticercosis in Bali, Indonesia. AB - Taenia solium and Taenia saginata are found in humans in Bali, Indonesia. During a field survey of 660 people in Bali from 2002-2009 of taeniasis/cysticercosis cases using mitochondrial DNA confirmation of the species, we detected 80 cases of T. saginata taeniasis, 2 dual T. saginata/T. solium infections with T. solium metacestodes in the brain and 12 neurocysticercosis (NCC) cases at Sanglah Hospital, Denpasar. Although the prevalence of NCC in Bali is low, sporadic cases are still present. There is no Taenia asiatica in Bali. We summarize here the field survey findings of taeniasis, including 1 dual infection with taeniasis and cysticercosis in 2007, and the reason why there are no T. asiatica cases and we describe 3 NCC cases admitted to Sanglah Hospital, Denpasar, Bali in 2004. Diagnosis was based on anamnesis, clinical examination, including CT Scan, histopathological, serological and mitochondrial DNA examinations. In order to prevent unexpected symptomatic NCC after treatment with praziquantel, we recommend introducing a rapid test to confirm taeniasis carriers and cysticercosis cases as a tool for real time diagnosis. PMID- 22299462 TI - Ectoparasites of small mammals in four localities of wildlife reserves in Peninsular Malaysia. AB - Field surveys of ectoparasites on rodents and scandents were conducted in four localities of wildlife reserves in Peninsular Malaysia from October 2008 to November 2009. A total of 16 animals comprising 5 species of hosts were caught and examined for ectoparasites. The hosts examined were Maxomys rajah, Maxomys whiteheadi, Leopoldamys sabanus, Lariscus insignis and Tupaia glis. Of these hosts, 9 genera, consisting of 14 species of ectoparasites were extracted. Three species of ticks (Ixodidae), 7 species of mesostigmatid mites (Laelaptidae), 3 species of chiggers (Trombiculidae) and 1 species of listrophorid mites (Listrophoriidae) were identified. The infestation rate of ectoparasites observed ranged from 12.5% to 62.5%. Among the ectoparasites found, Ixodes granulatus and Leptotrombidium deliense are of known medical importance. PMID- 22299463 TI - Insecticide susceptibility of the dengue vector, Aedes aegypti (L.) in Metropolitan Bangkok. AB - Mosquito larvae were collected from the houses of dengue infected patients in Bangkok, Thailand from 55 sites (36 out of the 50 districts of Metropolitan Bangkok). Aedes aegypti larvae were tested against temephos using WHO bioassay techniques. Adult mosquitoes were tested for susceptibility to permethrin, deltamethrin, cyfluthrin, malathion and DDT using WHO diagnostic doses. Most of the larvae tested were susceptible to temephos. Only few specimens were resistant to temephos. Most adult mosquitoes were highly susceptible to malathion. Deltamethrin resistance was seen in 6 districts of Bangkok. Variable levels of susceptibility were seen with cyfluthrin. Most of the specimens showed resistance to permethrin and all specimens were resistant to DDT. PMID- 22299464 TI - Clinical presentation and lung function of children hospitalized with 2009 pandemic influenza A (H1N1) pneumonia. AB - To determine the clinical presentation and subsequent lung function following pneumonia caused by 2009 pandemic influenza A (H1N1), pH1N1, in children aged 5 15 years hospitalized from June to September 2009, we contacted patients meeting the criterion 3-6 months post-hospitalization. Of the 88 patients contacted, 31 (35.2%) had pH1N1 and 57 (64.8%) had infections due to other viral pathogens (non pH1N1), the mean age was 10.4 years and 52 (59%) were boys. Compared to non-pH1N1 patients, the pH1N1 patients were more likely to have a high fever (96.8% vs 77.2%, p = 0.03), sore throat (58.1% vs 33.3%, p = 0.03), and injected pharynx (80.6% vs 40.4%, p = 0.001). At 3-6 months after pneumonia onset, means for FVC, FEV1, FEV1/FVC, FEF25-75%, and PEF were within normal limit in both the pH1N1 and non-pH1N1 groups. Five (28%) of 18 pH1N1 children and 4 (20%) of 20 non-pH1N1 children had abnormal lung function results. All were restrictive type. In conclusion, pH1N1 pneumonia were more likely to present with high fever, sore throat, and pharyngeal injection than pneumonia from other viruses. About one quarter of the children who had pH1N1 had restrictive lung function 3-6 months after infection. This number did not differ from the non-pH1N1 group. PMID- 22299465 TI - Response of health care workers with isolated antibody to hepatitis B core antigen to hepatitis B vaccine. AB - Isolated hepatitis B core antibody (antiHBc) without hepatitis B surface antigen (HBsAg) or hepatitis B surface antibody (antiHBs) is found during routine screening for hepatitis B virus (HBV) markers. Isolated antiHBc may indicate immunity against HBV or occult infection. To determine the immune response of health care workers (HCWs) with isolated antiHBc, HCWs were divided into two groups. A single dose of recombinant hepatitis B (HB) vaccine was administered to HCWs with isolated antiHBc (n = 36) and healthy HCWs (n = 20) seronegative for HBsAg, antiHBc and antiHBs. One month later, the subjects were tested for antiHBs. Twenty-one of 36 HCW (58.3%) in the antiHBc group had antiHBs, while only 1 of 20 HCW (5.0%) in the seronegative control group had a detectable antiHBs titer exceeding 10 mIU/ml. The antiHBs response in HCWs with antiHBc was significantly higher than in the seronegative group. The subjects' sera were tested for HBV DNA by nested PCR. Of those with antiHBc, 4 had detectable HBV DNA (occult HBV infection). None of these 4 responded to the vaccine. Therefore, the response elicited by a single dose of HB vaccine administered to patients with antiHBc may serve as an indicator of occult HBV infection. PMID- 22299466 TI - Evaluation of hepatitis A surveillance data and outbreak detection in Yunnan Province, China, from 2004 through 2009. AB - Hepatitis A outbreaks may be averted if detected early. The current study objectives were to evaluate the quality and timeliness of hepatitis A surveillance data from Yunnan Province, China, and to evaluate the sensitivity of the system for reporting outbreaks. The study period was from January 1, 2004 through December 31, 2009. Records from the National Infectious Diseases Surveillance System (NIDSS) were compared with those from local hospitals. The timeliness of case detecting, reporting and updating was also analyzed. The numbers of cases in a specific location during a moving time interval were computed to identify past outbreaks which were then validated against reported cases. The NIDSS received 38,095 reports during the study period; of which 6% were duplicates, and 26% had serological confirmation. The sensitivity and positive predictive value of cases were 96% and 98%, respectively. Time from onset to diagnosis remained constant over the 6-year period. Delays in reporting became shorter, and quality control of data improved over the period, but the timeliness of identifying duplicate records did not. Based on data from NIDSS, 9 outbreaks should have been reported, but only 3 were reported. The 3 reported outbreaks were shorter in duration than the 6 unreported ones, but the numbers of cases involved were not significantly different. Surveillance data needs improvement in updating timeliness. The system for outbreak detection and reporting needs to be improved. PMID- 22299467 TI - Genetic analysis of beak and feather disease virus isolated from captive psittacine birds in Thailand. AB - Beak and feather disease virus (BFDV) is a causative agent of psittacine beak and feather disease. Genome sequences of BFDVs isolated from Thailand have not hitherto been reported. The whole genomes of 17 BFDV isolates, obtained from 12 psittacine genera, were amplified and subjected to direct sequencing revealing a length ranging from 1,990 to 2,015 nucleotides. The predicted open reading frames (ORFs) in the viral genome varied from four to six. Only ORF1, ORF2, and ORF5 were found in all isolates. Deduced amino acid sequences of BFDV ORF2 were used to construct a phylogenetic tree. The phylogram grouped BFDV into ten clusters, which showed either host species relationship or regional restriction. The Thai isolates, were grouped into three clusters, cluster I, II, and V. Cluster I and II showed restricted geographical region to Thailand, and cluster II also showed a close relationship with BFDV isolated from Australia. Cluster V demonstrated neither restricted region nor species specificity of birds. In this cluster, there was an insertion of 16 nucleotides at non coding region of all BFDV isolates. The genetic information obtained from this study can be used to help understand BFDV diversity and evolution in Thailand. PMID- 22299468 TI - Impact of HIV-1 viral load on genotypic characteristics among patients failing non-nucleoside reverse trancriptase inhibitor-based first-line regimens in Northern Thailand. AB - Widespread use of antiretroviral drugs has significantly increased drug resistance. In the resource limited countries, delayed detection of drug resistance may lead to accumulation of drug resistance mutations. We investigated the genotypic drug resistance mutation patterns in HIV-infected patients with various levels of plasma HIV RNA levels. Fifty-nine HIV-infected patients with antiviral therapy failure were recruited. Genotypic assays of HIV-1 protease and reverse transcriptase genes were analyzed. There was a significant difference in CD4 cell counts and percentage of CD4 (p < 0.05) between groups of patients with high and low viral load, who failed first-line non nucleoside reverse transcriptase inhibitor-based regimens. In addition, patients with HIV-1 viral load > or = 4 log10 have a significantly higher likelihood of being infected with HIV-1 containing 3 to 5 resistance-associated mutations than those with HIV-1 viral load < 4 log10. Thus, delayed detection of increased HIV-1 viral load and antiretroviral drug-resistance may lead to accumulation of drug-resistant mutations and decreased CD4 cell count and percentage. PMID- 22299469 TI - Screening scheme development for active TB prediction among HIV-infected patients. AB - The objective of this study was to develop and evaluate a simple scoring scheme to screen for active tuberculosis (TB) among HIV-infected patients. Two hundred fifty-seven HIV-infected patients were enrolled in the study between April 2009 and May 2010 from Mae Sai District Hospital and Lampang Regional Hospital. Participants underwent routine evaluations to diagnose TB. Data collection included demographics, medical history, signs and symptoms and laboratory results. Of the 257 HIV-infected patients enrolled, 66 (25.7%) were diagnosed with active TB. Six variables were statistically significant predictors of active TB (p < 0.05): BMI < or = 19 kg/m2, cough > 2 weeks, shaking chills > or = 1 week not taking antiretroviral drugs, a CD4+ cell count level < 200 cells/microl, and had a history of TB. A risk score (ranging from 0 to 16) gave a 92.1% sensitivity of being associated with active TB. A low risk score (< or = 2.0), a moderate risk score (3.0-7.0), and a high risk score (>7.0) gave positive likelihood ratios (LHR+) of 0.04 (95% CI 0.01-0.24), 2.56 (95% CI 1.71-3.85), and 11.72 (95% CI 4.91-27.96), respectively. This screening tool may be useful to identify patients who should have further diagnostic testing for TB, but requires further validation before adoption due to the variability of predicting factors and the prevalence of TB in the target population. PMID- 22299470 TI - Association between circulating full-length osteopontin and IFN-gamma with disease status of tuberculosis and response to successful treatment. AB - The T helper type 1 (Th1) immune response plays an important role in protective immunity, pathophysiology and development of tuberculosis (TB). To investigate whether osteopontin (OPN) and other Th1 response-related molecules are associated withTB disease status, including co-infection with HIV, and response to anti-TB treatment, circulating levels of full-length OPN (F-OPN), thrombin-cleaved N terminal fragment of OPN (N-half OPN), IFN-gamma, IP-10, IL-18, IL-12/ IL-23 (p40), IL-10, IL-15 and C-reactive protein (CRP) were measured before and after anti-TB treatment. Patients with newly active pulmonary TB had significantly higher plasma levels of F-OPN, IFN-gamma and CRP than healthy controls (HC). F OPN, N-half OPN, IFN-gamma, IP-10, IL-18 and IL-10 levels were higher in patients with extensive TB/HIV co-infection than in patients with a single disease of TB or HIV. Plasma levels of F-OPN correlated well with those of IP-10, IL-18 and N half OPN among patients with active TB. The F-OPN, IFN-gamma, IP-10 and CRP levels decreased significantly after effective anti-TB treatment. These data suggest that circulating OPN and Th1 response-related molecules, including IFN gamma, may be regulated in response to expansion of active TB and could serve as markers of disease activity before and during treatment. PMID- 22299471 TI - In vitro activity of colistin or sulbactam in combination with fosfomycin or imipenem against clinical isolates of carbapenem-resistant Acinetobacter baumannii producing OXA-23 carbapenemases. AB - This study investigated the in vitro activity of colistin or sulbactam in combination with fosfomycin or imipenem against eight strains of carbapenem resistant A. baumannii (CRAB). The eight CRAB clinical isolates were collected from hospitalized patients admitted to Songklanagarind Hospital in southern Thailand during January-December 2008. The isolates were divided into 4 different patterns of clonal relationships using the Repetitive Extragenic Palindromic Polymerase Chain Reaction method (REP-PCR). The in vitro activity of combination antibacterial agents against theses isolates were determined by chequerboard and time-kill methods. All isolates producing OXA-23 carbapenemases were universally susceptible to colistin but intermittently susceptible to other antimicrobial agents. A chequerboard assay showed the synergistic effects of sulbactam plus fosfomycin and colistin plus fosfomycin in 75% and 12.5% of isolates, respectively. Sulbactam at a concentration of 1 x MIC plus fosfomycin at 1 x MIC or at 1/4 x MIC showed synergism in 75% and 37.5% of clinical isolates, respectively. Bactericidal activity was observed for up to 12 hours of incubation. There was no synergism between colistin and sulbactam, sulbactam and imipenem, and colistin and imipenem, against the tested isolates. Combined use of sulbactam and fosfomycin may provide an alternative therapeutic option for CRAB infections. PMID- 22299472 TI - Clinical features of gastrointestinal salmonellosis in children in Bangkok, Thailand. AB - This retrospective descriptive study was conducted at Queen Sirikit National Institute of Child Health (QSNICH), Bangkok, Thailand to describe the clinical features of gastrointestinal salmonellosis in children. The medical records of 134 patients admitted to QSNICH in 2009 who had a positive stool culture for Salmonella spp were reviewed. Demographic, clinical, laboratory, treatment, culture and antimicrobial sensitivity data were collected and analyzed. The mean age of the patients was 22.9 months (range 0.5 to 158 months); 76.9% were < 2 years old. The male to female ratio was 1.5:1. Salmonella B was most commonly found serogroup (47%). The common clinical manifestations included diarrhea (99.3%), fever (93.3%), dehydration (64.9%) and nausea/vomiting (48.5%). Most of the Salmonella isolates were sensitive to a fluoroquinolone and many were sensitive to Cotrimoxazole, but few were sensitive to ampicillin. There were no significant differences in the clinical manifestations and drug sensitivities of the different Salmonella serogroups, except convulsions were more common in Salmonella E infected patients (p = 0.04) and more Salmonella C isolates were sensitive to ampicillin (p = 0.04). There was no significant correlation between clinical course and antimicrobial treatment, except the duration of diarrhea was significantly longer in patients who received antimicrobial treatment (mean 6.1, SD 4.7 days vs mean 4.2, SD 2.1 days) (p = 0.03). Three patients had Salmonella bacteremia. Three patients died but not directly due to Salmonella infection. PMID- 22299473 TI - Streptococcus pneumoniae infections in western Nepal. AB - We conducted a study to determine the prevalence of antibiotic resistance among clinical isolates of S. pneumoniae. This study was conducted from January 2000 to August 2007 at a tertiary care teaching hospital in Nepal. The isolates were identified based on standard bacteriological techniques. Antibiotic susceptibility testing used the Kirby-Bauer disc diffusion method; penicillin resistance was confirmed by agar dilution method. During the study period, there were 312 S. pneumoniae isolates. Penicillin, trimethoprim-sulfamethoxazole, erythromycin, tetracycline and chloramphenicol resistance were observed in 5, 34.3, 7.4, 11.1 and 0.4% of isolates, respectively. Resistance to all tested antibiotics declined with time except for penicillin, in which resistance increased. Penicillin-resistant S. pneumoniae were significantly co-resistant to erythromycin. Co-resistance to tetracycline and erythromycin were observed in trimethoprim-sulfamethoxazole resistant isolates. Penicillin resistance is increasing; therefore, measures to ensure judicious use of beta-lactams and macrolides (inducers of penicillin resistance) should be advocated to control the development of penicillin-resistant S. pneumoniae. PMID- 22299474 TI - Adrenal histoplasmosis: a case series and review of the literature. AB - Adrenal histoplasmosis is an uncommon mycotic disease typically caused by Histoplasma capsulatum. The objective was to determine the clinicopathological findings in adrenal histoplasmosis. Pathological records were searched from the database at the Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University from 1993 to 2008 for cases of adrenal histoplasmosis. The keywords were "histoplasmosis" and "adrenal gland". Adrenal histoplasmosis was diagnosed by histopathology and Gomori-Grocott methenamine silver staining. Histoplasma capsulatum was confirmed by tissue culture and/or serology. The authors report seven cases of adrenal histoplasmosis in immunocompetent patients. The mean age at diagnosis was 67 years. All patients presented as chronic fatigue syndrome. The onset of symptoms ranged from one to three months. Addison's disease was found in adrenal histoplasmosis in one case (14.3%). The computed tomography revealed adrenal nodules measuring 1.2 to 7.8 cm in diameter. The histopathology showed granulomatous inflammation with caseous necrosis. Culture of adrenal tissue from two patients revealed Histoplasma capsulatum. Serum Histoplasma antibodies were positive in four cases. A cure was accomplished in 6 out of 7 cases (85.7%). The patients were followed up for 2.5 to 16.5 years. PMID- 22299475 TI - Assessment of appropriateness of restricted antibiotic use in Charoenkrung Pracharak Hospital, a tertiary care hospital in Bangkok, Thailand. AB - The purpose of this study was to evaluate the appropriate of restricted antibiotics at a tertiary care hospital in Bangkok, Thailand. Data from patient charts during September-November, 2009 were obtained regarding appropriate use of antibiotics following hospital antibiotic guidelines. Of 307 prescriptions reviewed, the prevalence of appropriate antibiotic use was 74.6% (229/307). Most patients were male (185/307) with a mean age of 64.2 +/- 18.0 years. There was a significant association between appropriate antibiotic use and patients having underlying disease, a previous history of recent antibiotic use, a recent hospitalization, admission to a medical unit and having a recent health-care institution acquired infection (p < 0.001). The diagnosis of pneumonia was associated with proper use of antibiotics compared with other diagnoses (OR 1.8). Admission to a medical ward was more likely to be associated with correct antibiotic use than having surgery (OR 7.8 and 0.07). Having a health-care institution acquired infection more likely to be associated with appropriate antibiotic use than having a community acquired infection (OR 5.5 and 0.13). Meropenem was more likely to be used appropriately than cefoperazone/sulbactam (OR 1.9 and 0.2). After multivariate analysis, controlling confounding factors, admission to a medical unit and having a health-care institution acquired infection were factors associated with proper use of restricted antibiotics (adjusted OR 9.0 and 7.1; 95% CI 2.27-35.73 and 2.38-20.95; p = 0.002 and p < 0.001, respectively). The prevalence of appropriate use of restricted antibiotics was high; physicians followed local hospital antibiotic guidelines. Future studies of compliance with hospital antibiotic guidelines and its impact on bacterial resistance and infection related mortality should be carried out to determine if appropriate antimicrobial use leads to improve outcomes. PMID- 22299476 TI - Association between retinol-binding protein and renal function among Asian subjects with type 2 diabetes mellitus: a cross-sectional study. AB - Retinol-binding protein 4 (RBP4) has been suggested as new adipokine, possibly linking obesity to type 2 diabetes mellitus (T2DM). Since the kidneys are the main site of RBP4 degradation and since renal failure is a frequent co-morbid condition with diabetes mellitus, we evaluated the association among RBP4, renal function and T2DM in an Asian population. RBP4 serum levels were analyzed in 110 subjects (50 with T2DM) using an enzyme-linked immunosorbent assay (ELISA). Based on a cut-off estimated glomerular filtration rate (eGFR) of 60 ml/min per 1.73 m2 (calculated according the abbreviated MDRD formula which uses serum creatinine level, age and gender) and on the T2DM status, subjects were assigned to four subgroups: Group A- controls with an eGFR > 60 ml/min per 1.73 m2, Group B - controls with an eGFR < 60 ml/min per 1.73 m2, Group C- T2DM subjects with an eGFR > 60 ml/min per 1.73 m2, and Group D - T2DM subjects with an eGFR < 60 ml/ min per 1.73 m2. In both the T2DM and control groups, RBP4 levels were higher in subjects with an eGFR < 60 ml/min per 1.73 m2 than in subjects with an eGFR > 60 ml/min per 1.73 m2. However, the difference was only significant between the control groups (p < 0.05). After adjusting for age, gender, BMI, eGFR and the presence of T2DM, eGFR, not T2DM, was associated with plasma RBP4 levels (p < 0.05). These results suggest among Asians the eGFR, but not the presence of T2DM, is a major determinant of RBP4 serum levels. The eGFR should be taken into account when evaluating the role of RBP4 in the pathogenesis of insulin resistance and T2DM. PMID- 22299477 TI - Toxicity from ingestion of Jatropha curcas ('saboo dum') seeds in Thai children. AB - Jatropha curcas is widely cultivated in Thailand, the seeds of which yield high quality oil used for biodiesel production. Toxicity due to ingestion of Jatropha curcas has become more common among children due to the close proximity between cultivation and residential areas. We report 10 calls made over a 40-month period to the Siriraj Poison Control Center involving 75 children ages 2-14 years who experienced toxicity after ingesting various amounts of Jatropha beans. The amounts ingested, presenting symptoms, pertinent laboratory findings and their collective dispositions are reported. A brief review of recent published literature on toxicity due to ingestion of Jatropha curcas was also done. PMID- 22299478 TI - Health-related quality of life in Thai thalassemic children treated with iron chelation. AB - Thalassemia is a chronic hereditary disease in which patients with severe disease present with anemia during their first year of life. In Thailand, stem cell transplantation is not an option for most patients. Supportive treatments, such as blood transfusions and iron chelation are used. Little data exists regarding the Health Related Quality of Life (HRQoL) of these patients. We conducted a study of the four dimensions of quality of life: physical, emotional, social, and role (school) functioning, using the PedsQL 4.0 Generic Core Scale to measure the HRQoL among thalassemic patients at the Hematology Unit, Department of Pediatrics, Phramongkutklao Hospital, during December 1, 2006 - November 30, 2007 to evaluate the quality of life in thalassemic patients treated with three iron chelating agents. Forty-nine thalassemic patients were enrolled and treated with iron-chelating agents. The mean (SD) age of the patients was 10.61 years (4.33). Fifteen thalassemic patients were treated with desferrioxamine, 18 with deferiprone and 16 with deferasirox. The quality of life (QOL) results show the mean (SD) total summary score was 74.35 (12.42). For the psychosocial health summary, the social and school functioning scores were 85.40 (16.67) and 62.14 (15.84), respectively. The QOL scores of the patients who received desferrioxamine, deferiprone and deferasirox were 75.29 (9.09), 73.91 (15.25) and 73.98 (12.32), respectively (p = 0.94). The QOL had no significant differences by age, gender, type of thalassemia or serum ferritin level. Multivariate regression analysis showed no significant differences in clinical severity, age of onset or pre-transfusion hematocrit levels. PMID- 22299479 TI - Fatal neurotoxic envenomation from the bite of a Lesser Black Krait (Bungarus lividus) in Nepal. AB - The Lesser Black Krait (Bungarus lividus) is a small, secretive, nocturnal elapid snake inhabiting Nepal, Bangladesh and India. We report a case of B. lividus bite in Nepal resulting in burning sensation at the bite site and over the whole body, abdominal pain, vomiting, slurred speech, ptosis, and progressive generalized neuromuscular paralysis leading to respiratory distress and death. Only one other case of fatal envenomation by this species has been reported previously in India. This demonstrates that B. lividus contributes to snakebite mortality in South Asia. As few snakebite victims in this region kill and bring the snake and because the clinical syndromes appear similar, envenomation by B. lividus may be misdiagnosed as envenomation by Common Kraits (Bungarus caeruleus). External morphology characters that distinguish B. lividus from B. caeruleus and other krait species are illustrated. PMID- 22299480 TI - Prediction equations for lung function in healthy, life time never-smoking Malaysian population. AB - Several equations have been used to predict lung function standard results for different populations. It is important lung function evaluations use appropriate standards for the study population. The objective of this study was to develop a prediction equation for lung function test results for the Malaysian population. Spirometry was performed among 5,708 subjects and 1,483 healthy, lifetime never smoked subjects (386 males and 1,097 females). Prediction equations were derived for both men and women for FVC and FEV1 results. The equations were validated on new subjects (n = 532, 222 males and 310 females) who met the same inclusion and exclusion criteria as the main cohort. There was a positive correlation between the measured values and the values derived from the new prediction equations (0.62 for FEV1 and between 0.66 and 0.67 for FVC; both p < 0.05) for both men and women with a smaller bias and limit of agreement compared to the published reference equations of ECCS, Knudson, Crapo and NHANES III. The reference equations derived from local spirometry data were more appropriate than generally used equations based on data from previous studies in different population. PMID- 22299481 TI - Association between cigarette smoking and socio-demographics, lifestyle and mental health factors in a sampled Iranian population. AB - The objective of this study was to evaluate associations between cigarette smoking and socio-economic variable in an Iranian male population. Isfahan Healthy Heart Program (IHHP) is a community oriented health study from which we obtained our data regarding male subjects. Socio-demographic variables--sex, age, marital status, educational level, occupation, and income--and physical activity level were derived from the questionnaire. Nutritional status was asked by the Food Frequency Questionnaire and the general dietry index (GDI) was calculated. A general health questionnaire (GHQ) comprised of 12 items was used to assess mental health. Smoking status was investigated by a self reported questionnaire as a dependent variable. A logistic regression model was used for statistical analysis. Current smokers comprised 26.2% of respondents while 8.5% were ex smokers. High income (OR 2.04; 95% CI 1.13-3.67), GDI (OR 1.83; 95% CI 1.44-2.32) and high stress (GHQ > or = 4 OR 1.71; 95% CI 1.48-2) were associated with smoking. Older age (OR 0.991; 95% CI 0.985-0.998), university education level (OR 0.53; 95% CI 0.37-0.77), unemployment (OR 0.8; 95% CI 0.64-0.99) and obesity (BMI > or = 25 kg/m2 OR 0.63; 95% CI 0.55-0.73) were associated with non-smoking status. Our findings confirm an association between socio-demographics, lifestyle and mental health variables with smoking in the Iranian population, consistent with other studies worldwide. These factors should be considered when developing smoking cessation strategies. PMID- 22299482 TI - Factors affecting failure to quit smoking after exposure to pictorial cigarette pack warnings among employees in Thailand. AB - This study was carried out to determine whether health warning pictures(HWP) affect smoking cessation using a structured equation model for intending-to-quit smokers in work places. Data from a 1-year longitudinal followup of attempt-to quit employees was obtained to determine if pack warnings affect tobacco cessation rates. Stratified simple random sampling, and Structured Equation Modeling (SEM) were employed. Approximately 20% of intending-to-quit smokers were successful. The integrated model, combining internal, interpersonal factors and health warning pictures as external factors, fit the fail to quit pattern of the model. Having a smoking father was the most significant proximate indicator linked with failure to quit. Although HWL pictures were an external factor in the decision to stop smoking, the direct and indirect causes of failure to quit smoking were the influence of the family members. Fathers contributed to the success or failure of smoking cessation in their children by having an influence on the decision making process. Future HWP should include information about factors that stimulate smokers to quit successfully. The role model of a father on quitting is also important. PMID- 22299483 TI - Stress and its relief among undergraduate dental students in Malaysia. AB - This study was conducted to identify the prevalence of stress, types of stressors, consequences of stress and stress relievers among undergraduate dental students at the University of Malaya during the different years of study. A descriptive cross-sectional quantitative study was conducted using a self administered questionnaire among Bachelor of Dental Surgery students during Years 2 to 5. A 100% response rate was obtained. The instrument asked questions about the preceding academic year. The results of the questionnaire reveal the prevalence of stress was 100%. The most common cause of stress among preclinical students was academic concerns and among clinical students was patient management and clinical performance. Physical and behavioral problems were reported as consequences of stress. Most students overcame stress by having strong interpersonal relationships. PMID- 22299484 TI - Factors related to community participation by stroke victims six month post stroke. AB - Participation in the community socially by stroke victims is an optimal outcome post-stroke. We carried out a cohort study to evaluate a model for community participation by Thai stroke victims 6 months post-stroke. Six standardized instruments were used to assess the patient's status 1, 3 and 6 months after stroke. These were the modified Rankin Scale, the National Institute of Health Stroke Scale, the Fugl-Meyer Assessment and the Berg Balance Scale. The performance of activities of daily living and community ambulation were measured using the Barthel Index and walking velocity. Participation in the community was measured by the Stroke Impact Scale. The outcomes demographics and stroke related variables were analyzed using the Generalized Estimating Equations. Of the 98 subjects who completed the follow-up assessment, 72 (86.5%) felt they had more participation in the community 6 months post-stroke. The level of disability, performance of independent activities and length of time receiving physical therapy were associated with the perceived level of participation in the community among stroke victims 6 months post-stroke. To achieve a goal of good participation in the community among stroke victims, health care planning should focus on improving the stroke victim's ability to independently perform daily activities. The average length of physical therapy ranged from 1 to 6 months, at 3 to 8 hours/month. Clinical practice guidelines should be explored to optimize participation in the community. PMID- 22299485 TI - Community awareness and perceptions of health sector preparedness and response to Cyclone Nargis. AB - Community awareness, preparedness and response to public health emergencies are essential for a successful response to public health emergencies. This study was carried out to determine community awareness and perceptions regarding health sector preparedness and response to Cyclone Nargis in Myanmar. Six focus group discussions were carried out in 3 villages severely affected by Cyclone Nargis. Thematic content analysis was carried out to determine community perceptions. Focus group participants, consisting of community members, community leaders and government personnel, were aware of the cyclone, but were unaware of its intensity and where it would make landfall. There was inadequate knowledge on how to prepare for a cyclone. There was some training on cyclone preparation but coverage was not wide enough. Participants received service and relief from health sector; they had a positive attitude toward health services provided to them. However, 5 out of 6 focus groups stated most villagers were not interested in health education. Only a few participants had some knowledge on how to prepare for a cyclone. Based on these results, there are evident weaknesses on how to prepare for cyclones. Community preparedness is essential to prevent disasters with cyclones, such as with Cyclone Nargis. PMID- 22299486 TI - Factors associated with use of improved water sources and sanitation among rural primary schoolchildren in Pursat Province, Cambodia. AB - Access to improved water supplies and sanitation generally reduces childhood diarrhea incidence. Using a cross-sectional stratified cluster sampling design, interviews were conducted among grade 4-6 primary schoolchildren from 10 primary schools in highland and lowland districts of Pursat Province, Cambodia, in both June (rainy season) and December (dry season) 2009 to determine the demographics and water sources/sanitation used. Parents also recorded any incidents of diarrhea in their children over those months. We explored the sociodemographic factors associated with use of improved water sources/sanitation, using mixed effect modelling. Participation was 84.7% (1,101/1,300). About half exclusively used improved water sources but less than 25% had access to improved sanitation during both seasons. Adjusting for clustering within households and within individuals over time, exclusive use of improved water sources and sanitation were associated with the following: dry season, more permanent housing type, family size < 8 members, and higher levels of education. Exclusive use of improved sanitation was associated with good hygiene practices and exclusive use of improved water sources was associated with male gender. Access to improved water sources and sanitation among rural Cambodian primary schoolchildren can be improved, particularly in those with lower socio-economic status. Programs to promote use of improved water sources/sanitation need to target less educated parents. PMID- 22299487 TI - The effect of casein phosphopeptide toothpaste versus fluoride toothpaste on remineralization of primary teeth enamel. AB - This study evaluated the effect of a CPP-containing toothpaste and compared it with fluoride-containing toothpastes on remineralization of caries-like lesions in primary teeth enamel, using polarized light microscopy. Forty-eight sound primary incisors were coated with nail varnish, leaving two 1x1 mm windows before being placed in a demineralizing solution for 4 days. After demineralization, all the specimens were coated with nail varnish over one window and were randomly assigned to 4 groups (A to D; n = 12). Group A teeth were exposed to distilled water. Group B teeth were exposed to a CPP-containing toothpaste (Hi Herb). Group C teeth were exposed to a 260 ppm fluoride-containing toothpaste (Smile baby toothgel). Group D teeth were exposed to a 500 ppm fluoride-containing toothpaste (Oralmed Kid). Polarized light microscopy was used to evaluate lesion depth, before and after a 7-day pH cycle. Lesion depth was measured using a computerized method with the Image-Pro Plus program. Differences in mean lesion depth within groups and between groups were analysed using the paired t-test, Kruskal-Wallis test and Mann-Whitney U test at a 95% level of confidence. Mean lesion depths in Groups A, B, C and D significantly increased by 110.1, 36.1, 40.2 and 18.2%, respectively. The mean lesion depths for all the toothpaste groups (B, C and D) were significantly different from the control group (A). Comparisons made among treatment groups showed Group D was significantly different from Groups B and C. All toothpastes were effective for inhibiting progression of carious lesions. However, a 500 ppm fluoride-containing toothpaste inhibited lesion progression better than a CPP-containing toothpaste and a 260 ppm fluoride-containing toothpaste. PMID- 22299488 TI - Cell distraction. Professional etiquette for cell phones. PMID- 22299489 TI - Analysis paralysis. Here are five ways to avoid this potentially fatal career condition. PMID- 22299490 TI - Special delivery. Blizzard operations limit a pregnant patient's choices. PMID- 22299491 TI - Chest assessment. Containing important organs, it can hold the key to many problems. PMID- 22299492 TI - Healthcare policy development. Q&A with Gregg Margolis, PhD. interview by Jenifer Goodwin. PMID- 22299493 TI - The show that started it all. Emergency! Debuted 40 years ago this month. PMID- 22299494 TI - A service looks at 40. Acadian helps define EMS in the Gulf area. PMID- 22299495 TI - How to manage the pediatric airway. Training for these critical calls is vitally important. PMID- 22299496 TI - The physiology of respiration. Patients experiencing difficulty breathing can prove challenging to assess in the prehospital environment. PMID- 22299497 TI - Oxygen toxicity. What EMS providers need to know about possible complications from oxygen administration. AB - The administration of oxygen is safe and effective for patients who are in respiratory distress or who are hypoxic. Never feel that oxygen needs to be withheld. However, keep in mind that there are real consequences to the long-term utilization of high-flow oxygen. To help prevent potential complications from oxygen administration, reach for the nasal cannula before the non-rebreather mask, and apply just enough oxygen to maintain normal saturations. PMID- 22299498 TI - Trick or trivia. What should test questions really cover? PMID- 22299499 TI - Improving your spatial IQ can lift your social IQ. PMID- 22299500 TI - What business schools can learn from the medical profession. PMID- 22299501 TI - Candor, criticism, teamwork. PMID- 22299502 TI - Gilt Groupe's CEO on building a team of A players. AB - Ryan believes that a CEO should spend more time on recruiting and managing people than on any other activity, and that the head of HR is one of the most important people in the company. He insists on his freedom to bypass managers and speak with any employee at any time. And he espouses certain talent-management principles, such as that your best people are usually underpaid (reward them with performance pay) and that people leave jobs mainly because they don't like their managers. Recruiting at Gilt Groupe focuses on references more than on resumes and interviews because, Ryan says, resumes only establish basic qualifications for a job, and interviewers can't help being influenced by well-spoken or attractive people. But reference checks need to go beyond the names supplied by a candidate: Employers should dig up people in their networks who are willing to speak candidly. PMID- 22299503 TI - Die the way you want to. PMID- 22299504 TI - Pay businesses to keep people out of prison. PMID- 22299505 TI - The economics of well-being. AB - Gross domestic product has long been the chief measure of national success. But there's been a lot of talk lately about changing that, from economists and world leaders alike. GDP is under siege for three main reasons. First, it is flawed even on its own terms: It misses lots of economic activity (unpaid household work, for example) and, as a single-number representation of vast, complex systems, is inevitably skewed. Second, it fails to account for economic and environmental sustainability. And third, readily available alternative measures may reflect well-being far better, by taking into account factors such as educational achievement, health, and life expectancy. HBR's Justin Fox surveys historical and current views on how to assess national progress, from Jeremy Bentham to Robert Kennedy to Nicolas Sarkozy. He also looks at where we may be headed. The biggest success so far in the campaign to supplant or at least supplement GDP, he finds, is the UN's Human Development Index-on which the United States has never claimed the top spot. PMID- 22299506 TI - The science behind the smile. Interview by Gardiner Morse. AB - Only recently have we been able to apply science to one of the world's oldest questions: "What is the nature of happiness?" In this edited interview, the author of the 2006 best seller Stumbling on Happiness surveys the field. Gilbert explores the sudden emergence of happiness as a discipline, reviews the major findings (including the mistakes we all make in predicting how happy or miserable we'll be), and examines the role of happiness in productivity on the job. He describes what makes us truly happy-it's not a promotion or a new house-and sketches out a "happiness diet" that emphasizes small, routine efforts. Looking forward, Gilbert discusses the breakthrough work of his colleague Matthew Killingsworth, whose iPhoneenabled real-time surveys of people's moods are providing an ultra-high-resolution picture of how our emotional states shift from minute to minute. A sidebar by Killingsworth offers a preliminary look at his findings and their implications for our personal and workplace lives. PMID- 22299507 TI - The future of happiness research. PMID- 22299508 TI - Creating sustainable performance. AB - What makes for sustainable individual and organizational performance? Employees who are thriving-not just satisfied and productive but also engaged in creating the future. The authors found that people who fit this description demonstrated 16% better overall performance, 125% less burnout, 32% more commitment to the organization, and 46% more job satisfaction than their peers. Thriving has two components: vitality, or the sense of being alive and excited, and learning, or the growth that comes from gaining knowledge and skills. Some people naturally build vitality and learning into their jobs, but most employees are influenced by their environment. Four mechanisms, none of which requires heroic effort or major resources, create the conditions for thriving: providing decision-making discretion, sharing information about the organization and its strategy, minimizing incivility, and offering performance feedback. Organizations such as Alaska Airlines, Zingerman's, Quicken Loans, and Caiman Consulting have found that helping people grow and remain energized at work is valiant on its own merits-but it can also boost performance in a sustainable way. PMID- 22299509 TI - Positive intelligence. AB - Most of us assume that success will lead to happiness. Shawn Achor, founder of the corporate strategy firm Good Think, argues that we've got it backward; in work he's done with KPMG and Pfizer, and studies he's conducted in concert with Yale's psychology department, he has seen how happiness actually precedes success. Happy employees are more productive, more creative, and better at problem solving than their unhappy peers. In this article, Achor lays out three strategies for improving your own mental well-being at work. In tough economic times, they're essential for keeping yourself-and your team-at peak performance. PMID- 22299510 TI - The history of happiness. AB - In the 18th century, the Enlightenment ushered in the notion that happiness was the attainment of a worthy life. Since then the pursuit of happiness has spread to every aspect of behavior, from religion and politics to work and parenting. Today the happiness imperative creates pressures that, paradoxically, can make us miserable. Sadness is often mistaken for a pathology. Understanding the cultural commitment to good cheer as an artifact of modern history, not as an inherent feature of the human condition, opens new opportunities for understanding key facets of our social and personal experience. PMID- 22299511 TI - Why "good jobs" are good for retailers. AB - Too many retail managers believe that they must offer bad jobs to keep prices low. As a result, almost one-fifth of American workers suffer low wages, poor benefits, constantly changing schedules, and few opportunitie for advancement. The author's research reveals, however, that the presumed trade-off between investment in employees and low prices is false. To meet short-term performance targets, many retailers cut labor. The unmotivated and poorly trained employees who remain often cannot keep up with their tasks in a complex operating environment. The result is a vicious cycle, in which lower sales and profits tempt managers to cut even more employees. Retailers such as QuikTrip, Mercadona, Trader Joe's, and Costco instead create a virtuous cycle of investment in employees, stellar operational execution, higher sales and profits, and larger labor budgets. They also make work more efficient and fulfilling for employees, improve customer service, and boost sales and profits through four practices: simplify operations by offering fewer products and promotions, train employees to perform multiple tasks, eliminate waste in everything but staffing, and let employees make some decisions. PMID- 22299512 TI - Three skills every 21st-century manager needs. AB - Over the past decade companies have become more global and employee groups more diverse than ever before. Organizations are less hierarchical and more collaborative. And today's offices are full of once unimaginable technological distractions. We asked experts in cross-cultural communication, information networks, and the science of attention what skills executives should cultivate to tackle these new challenges. Molinsky thinks that managers must overcome psychological barriers in order to act in ways that other cultures find appropriate. Davenport and Iyer explain why the devolution of hierarchy has increased the value of building and wielding influence through digital networks and offer tips for how to do it. And Davidson tells managers to get over their fears about distraction and embrace the brain's natural tendency to divide attention. PMID- 22299513 TI - Code switching between cultures. PMID- 22299514 TI - Dividing attention deliberately. PMID- 22299515 TI - Generation robot. PMID- 22299516 TI - Industrial evolution. PMID- 22299517 TI - Why you should blame Wall Street for pharma's startup problem. PMID- 22299518 TI - [Morphologic changes of anterior segment of the eye after cataract surgery]. AB - OBJECTIVES: The goal of our study was to evaluate the changes of the anterior chamber and how these changes influence the intraocular pressure in patients, with diagnosed cataract only and with patients with cataract and angle closed glaucoma. MATERIAL AND METHODS: In this study 82 eyes in 82 patients were involved, who were divided into two groups. The first one, consists 60 of patients only with cataract and the second one consists 22 of patients with cataract and closed-angle glaucoma. We have measured the depth of the anterior chamber and the width of the iridocorneal angle with the help of anterior chamber optic coherent tomography and the intraocular pressure before and five weeks after the cataract surgery. RESULTS: Anterior chambers of all patients were deeper after cataract surgery. In the first group, patients only with cataract, the anterior chamber were deeper of 1.4 mm and in the second group the anterior chamber were deeper of 1.5 mm. The iridocorneal angle has opened at 3 o'clock from 23.2 +/- 9.5 degrees to 35.5 +/- 6.8 degrees and at 9 o'clock from 23.7 +/- 8.8 degrees na 36.4 +/- 7.9 degrees in the first group. Same changes were evaluate in patients with angle closed glaucoma at 3 o'clock the angle deepened from 18.5 +/- 10.0 degrees to 31.7 +/- 7.0 degrees and at 9 o'clock from 20.3 +/- 10.2 to 34.6 +/- 7.6 degrees. The values of intraocular pressure decreased from 14.8 +/- 3.6 mmHg to 13.3 +/- 2.9 mmHg in cataract only group and from 17.9 +/- 4 mmHg to 15.9 +/- 3.8 mmHg in the second group respectively. The deepening of the anterior chamber and opening of the iridocorneal angle with decreasing of the intraocular pressure after the cataract surgery are statistically significant P < 0.001. CONCLUSIONS: Cataract surgery deepen the anterior chamber significantly, it wides the iridocorneal angle and lowers intraocular pressure. PMID- 22299519 TI - [Benefit of paint diode laser coagulation in the treatment of ROP]. AB - PURPOSE: Authors compare results of ROP treatment with a single spot diodlasercoagulation (DLC) versus paint--DLC. METHODS: A retrospective chart review of patients with threshold retinopathy of prematurity treated between 2001 2010 was conducted. A single spot DLC was used from January 2001 to May 2008. In this group (SI) there were 338 patients (671 eyes) with ROP. In the second group (S II) since June 2008 to June 2010 we have used the paint DLC in 158 patients (316 eyes). Authors compare the need for reoperations to achieve regression of ROP in both groups. Rate of progression, frequency of retreatment, complications and structural outcomes were evaluated. RESULTS: In SI was retreatment only with DLC necessary in 43 eyes (6.4%). Additional cryotherapy was used in 22 eyes (3.3%). A scleral buckling was used in 107 eyes (15.9%). In S II was retreatment with DLC used in 4 eyes (1.3%), the additional cryotherapy in 6 eyes (1.9%) and the scleral buckling in 11 eyes (3.5%). CONCLUSION: According to our outcomes we have found out the paint DLC mode is more effective than the single spot DLC in the ROP treatment. PMID- 22299520 TI - [Long term results of laser refractive operations--methods Epi-LASIK or LASEK]. AB - PURPOSE: To compare and evaluate postoperative results of two methods of refractive laser surgery, Epi-LASIK and LASEK, performed at the Department of Ophthalmology and Optometry of St. Anne's University Hospital Brno, Czech Republic. METHODS: 128 eyes operation were performed on patients with myopia, 102 with the Epi-LASIK method and 26 with the LASEK method. The preoperative mean spherical equivalent was -4.8 +/- 2.6 D (range -2.3 to -7.5) in the Epi-LASIK eyes and -3.5 +/- 3.1 D (range -1.6 to -7.8) in the LASEK eyes. The average preoperative uncorrected visual acuity (UCVA) was 0,129 (from 0.02 to 0.8) with the Epi-LASIK method and 0,246 (from 0.02 to 0.8) with the LASEK method. The best average corrected visual acuity was 1,139 (from 0.63 to 1.6) with the Epi-LASIK method and 1.115 (from 0.25 to 1.25) with the LASEK method. The average cylindrical refraction of the Epi-LASIK patients before the operation was -1.52 +/- 0.80 D (range -1.0 to -3.5) and the LASEK patients was -1.55 +/- 0.89 D (range -1.0 to -3.0), except of those who have astigmatism up to +/- 0.75D. In both methods was used the excimer laser Mel 80 Meditec-Zeiss with 193 nm wavelength and the frequency of 250 Hz and active eye-tracking system. RESULTS: The postoperative mean spherical equivalent was 0 +/- 0.5 D (range -0.6 to 0.6) in the Epi-LASIK eyes and 0.3 +/- 0.4 D (range -0.3 to 0.7) in the LASEK eyes. The average uncorrected visual acuity was 0.745 with Epi-LASIK and 0.687 with LASEK after first week, 0.996 and 1,083 after month, 1.068 and 1.063 after 3 months, 1.147 and 1,082 after 6 months, 1.090 and 1.031 after one year. The average cylindrical refraction after the operation was -0.82 +/- 0.69 D (range 0 to -1.7) with Epi-LASIK and -0.59 +/- 0.55 D (range 0 to -1.5) with LASEK. Average "haze", evaluated by the Gartry's scale, was 0.39 with Epi-LASIK and 0.46 with LASEK after week, 0.21 and 0.06 after one year. CONCLUSIONS: The Epi-LASIK and LASEK methods have comparable postoperative results of visual acuity, astigmatism, "haze". They are effective too in worse form of the myopia. PMID- 22299521 TI - [Innovations in the treatment of the macular edema in retinal venous occlusions]. AB - The authors present new possibilities in the treatment of the macular edema caused by the retinal venous occlusions; these occlusions are the second most common retinal vessel disease. The earlier possibilities of the treatment were focused on the macular edema laser treatment, laser panretinal photocoagulation in case of retinal or iris neovascularization presence, and the disease's risk factors compensation. In the presence, the intravitreal application of corticosteroids or anti VEGF A preparations are more used for the treatment because of better results, as proved by means of randomized, clinical studies. PMID- 22299522 TI - [Corneal ulceration complicating surgical correction of ptosis in patient with Kearns-Sayre syndrome--a case report]. AB - The aim is to report a rare complication of surgical ptosis correction in a patient with Kearns Sayre syndrome and the therapeutic possibilities of its treatment. METHODS: Exposure corneal ulceration caused by lagophtalmos developed gradually in a 30-year-old woman after an upper eyelid ptosis surgery of the right eye performed at another eye clinic. During an examination a limited movement of both eyes and retinal pigmentary changes (salt-pepper-like appearance) were diagnosed. A suspicion of the Kearns Sayre syndrome was expressed according to the clinical picture, the diagnosis was confirmed by molecular analyses in muscle biopsy, which revealed 5.2 kb deletion of mitochondrial DNA. RESULTS: Corneal ulceration was treated by partial external tarsorrhaphy and frequent instillation of lubricants. The upper eyelid ptosis of the left eye was treated with a spectacle with ptosis support. CONCLUSION: During the correction of upper eyelid ptosis in patients with progressive external ophtalmoplegia it is necessary to be aware of the risk of surgical exposure keratopathy and corneal ulceration due to the atony of musculus orbicularis oculi muscle and only slightly expressed Bell's phenomenon. PMID- 22299523 TI - [Unilateral cystoid macular edema induced by citalopram--a case report]. AB - Citamopram is an antidepressant drug with fatigue, sleep disorders, appetite changes and visual impairment being the most common side effects. We are not aware of any published cases of cystoid macular edema following medication of this drug. We present a case of 55 year old woman with medical history of depression placed on Citalopram medication who noticed deterioration of right eye vision. Best corrected visual acuity was 20/120, ophthalmic coherence tomography and fluorescein angiography revealed cystoid macular edema. Two months following drug withdrawal edema disappeared and best corrected visual acuity improved to 20/32. Due to lack of other probable causes of edema and quick disappearance following drug withdrawal it is plausible to think of Citalopram as causative factor of cystoid macular edema in this patient. PMID- 22299524 TI - [Retinitis septica Roth--a case report]. AB - We report of a case of retinitis septica in a 37-years old man one month after his tooth's extraction. Because of decreased right eye's central vision and a presence of typical retinal Roth's spots we called internists for a possibility of bacterial endocarditis. Cardiologic examination confirmed this disease together with aortal valve's defect. The course of hearth's disease was weary heavy, with attack of septic fever and cardial decompensation. After acute stage control, defocusation and antibiotic therapy, he underwent a surgical intervention with exchange of aortal valve. PMID- 22299525 TI - [Current problems in the diagnosis and treatment of patients with myocarditis]. AB - Myocarditis as inflammatory cardiomyopathy is considered to be the primary group acquired cardiomyopathy. It is a disease of diverse etiology, which involves inflammation cardiomyocytes, interstitial tissue, vessels and sometimes the pericardium. The prevalence is not accurately known. Myocarditis is caused by many etiological factors: viruses, bacteria, protozoa and parasites. The presence of eosinophilic myocarditis is related to chemical compounds, including many drugs. This disease, although known for a long time still poses many problems in everyday medical practice. Clinical course of the disease and frequent process of transition dilated cardiomyopathy, tends to isolate the three phases of the disease: viral, autoimmune and dilated cardiomyopathy. These phases arise from the close link between viral infection and the accompanying immune response (especially contagious infection). In fact, the secondary immune response leads to activation of cytotoxic cells (CD8), which gives rise to antibodies directed against cardiomyocytes. Diagnosis of this disease is difficult and expensive, uses methods: direct (culture), molecular (PCR, hybridization) and imaging methods (echocardiography, MRI). Treatment of myocarditis depends on the phase and the etiology of the disease. In phase includes nonspecific viral antiviral agents, and avoidance of potentially harmful immunosuppression. The therapy is used among other immunoglobulins, statins, and patients in the phase dilated cardiomyopathy should be treated as idiopathic dilated cardiomyopathy and congestive heart failure. Myocarditis is one of the few units of cardiac disease for which there are no uniform standards of medical practice. PMID- 22299526 TI - [Concentrations of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-1 in serum of patients with chronic obstructive pulmonary disease]. AB - Chronic obstructive pulmonary disease (COPD) is characterized by the progressive destruction of the extracellular matrix of the lung. Matrix metalloproteinases (MMPs) and their inhibitors, especially tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), play a central role in the lung remodeling in COPD. Their concentrations in the sputum and bronchoalveolar lavage are considered as a sign of the local inflammation in COPD patients. The aim of the study was to evaluate of the MMP-9 and TIMP-1 serum concentration in COPD patients with respect to the correlation with a systemic inflammatory process. MATERIAL AND METHODS: Thirty six COPD patients (29 male and 7 female) were enrolled into the study. Age-matched, healthy 15 subjects (11 male and 4 female) were selected as a control group. Serum levels of MMP-9, TIMP-1 and CRP were measured. The pre- and post-bronchodilator forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio were determined. The Spearman correlation was performed. RESULTS: The serum MMP-9 concentration was significantly higher in the COPD patients than that in the control group (COPD: 194.8 +/- 129.1 ng x ml(-1); control subjects: 11.7 +/- 2.1 ng x ml(-1); p < 0.001). The serum concentration of CRP was significantly higher in the COPD patients than that in the control group (COPD: 14.3 +/- 6.3 ng x ml(-1); control subjects: 6.2 +/- 2.8 ng x ml(-1); p < 0.001). There was statistically significant correlation between the MMP-9 concentration and the CRP level in the serum of patients with COPD (p < 0.01; r = 0.45). There were no significant differences in the serum TIMP-1 concentrations between the control group and COPD patients. There was statistically significant, negative correlation between the FEV1 % of predicted value and the MMP-9 concentration (p = 0.03; r = -0.43). CONCLUSIONS: MMP-9 may play an important role in the systemic inflammatory process in COPD. The serum concentrations of MMP-9 correlate with the stage of COPD. PMID- 22299527 TI - [Respiratory functional impairment in patients with liver cirrhosis]. AB - End stage of liver disease can cause the respiratory tract dysfunction. Early diagnosis of hepatopulmonary syndrome can affect the therapy and determine the timing and risks of orthotopic liver transplantation. The aim of the study was to determine the respiratory distress in relation to liver damage assessed with scoring scales of Child-Pugh, MELD, GAHS, as well as fibrinogen and albumin levels. MATERIAL AND METHODS: Respiratory disorders were diagnosed by spirometry and plethysmography. The study included 71 patients with alcoholic liver cirrhosis. The results obtained were analyzed using the nonparametric Spearman correlation test and U-Mann-Whitney test. RESULTS: Analysis showed that the severity of liver damage leads to significant deterioration in DLCO/VA, (Child Pugh: r = -0.22; p < 0.04; the concentration of albumin: r = -0.24; p < 0.03). Depending on the scale GAHS correlation between the severity of liver failure and the deterioration rate Tiffeneau (FEV1/VC; r = -0.30; p < 0.004), reduction in TGV (r = -0.39; p < 0.0004), TLC (r = -0.27; p < 0.01) and RV (r = -0.31; p < 0.004) has been observed. CONCLUSIONS: Among patients with liver cirrhosis there are mainly restrictive pulmonary disorders and the difficulty of gas diffusion in the alveoli. These disorders correlate with the severity of liver damage assessed with Child-Pugh or GAHS classifications and albumin concentration. PMID- 22299528 TI - [Superior mesenteric artery syndrome--rare case report]. AB - Superior mesenteric artery syndrome is a condition caused by the compression of the third part of the duodenum between the superior mesenteric artery and the aorta. We present the clinical case of a patient, a female, 18 years old, with history of two days' evolution characterized by postprandial epigastric colic, accompanied by nausea and intractable vomiting. Applied conservative management was insufficient. The patient was successfully treated with open duodenojejunostomy. PMID- 22299529 TI - [Mediastinal neuroendocrine tumor (atypical carcinoid probably of thymic origin) imitating teratoma--case report]. AB - 67-year old man in a good physical condition was admitted to the Clinic to diagnose mediastinal tumor which was noticed on chest radiogram. The patient reported chronic cough, sweats and weight loss (5 kg during 4 months). The elevated number of monocytes was the only abnormality in his laboratory tests. Chest computer tomography confirmed well separated solid tumor without calcifications (with focal necrosis) in anterior mediastinal area. No lymphadenopathy was observed. Radiological image suggested teratoma or other germ stem tumor. Considering undiagnostic bronchial forceps biopsy during bronchofibroscopy we performed percutaneous fine needle aspiration biopsy which suggested carcinoid. Patient was referred to Surgery Clinic to be operated. Histological examination of resected tumor showed atypical carcinoid of probably thymic origin. PMID- 22299530 TI - [Arterial thyroid embolization in thyroid diseases]. AB - Traditional forms of treatment of the thyroid diseases: pharmacotherapy, radioiodine therapy and surgery can not always be applied. Intolerance, side effects of antithyroid drugs, low iodine uptake, high risk of surgery or disagreement with the proposed treatment was the reason for seeking alternative healing methods. With the development of interventional radiology, and gained experience in the use of arterial embolization, this method has become possible to use in treatment of thyroid diseases. The essence of this treatment is to shut down blood flow in major arteries of the thyroid by direct injection into the vessel's light of adequate size particles containing polyvinyl alcohol (PVA). The consequence of acute ischemia is septic necrosis of the glandular tissue in a field being supplied by this artery. Further repair processes and fibrosis lead to a reduction of active thyroid hormone synthesis and restriction of thyroid gland. Effects of embolization on angiogenesis, apoptosis and autoimmune reactions contribute to compensation thyroid function and significant reduction a goiter volume in course of Graves' disease. Preoperative selective embolization of a huge goiter or thyroid cancer improves surgery outcomes, reduces the risk of hemorrhage and damage to surrounding tissue. Palliative use of embolization in advanced stages of thyroid cancer reduces symptoms and improves quality of life. Little invasive nature of this procedure, the lack of serious undesirable coincidence makes embolization of thyroid arteries an attractive form of a therapy, which may become a therapeutic option in many difficult clinical situations and improve the clinical effectiveness of treatment of thyroid disease. PMID- 22299531 TI - [Contemporary determinations of sarcoidosis ethiopathogenesis]. AB - Sarcoidosis is a disease about unknown etiology. It's characterized by a chronic inflammation with creation of granuloma consisted of macrophages, lymphocytes and epithelial cells. The course of the disease may be different--from spontaneous remission to severe and chronic form. The most possible cause of sarcoidosis seems to be genetic etiology. Many trials indicated strong influence of human leukocyte antigens (HLA), cytokines and chemokines on sarcoidosis origin. On the other side the role of environmental factors, viral, atypical bacterial and mycobacterial infections is strongly stressed. PMID- 22299532 TI - [Theoretical and clinical aspects of tiotropium application as a first line therapy in stable state of all stages of chronic obstructive pulmonary disease]. AB - Current guidelines ERS, ATS, GOLD recommend use of one or more inhaler long acting bronchodilators to alleviate symptoms and reduce risk of exacerbations for the symptomatic patients with moderate to severe in stabile COPD. Since parasympathetic activity is the dominant reversible component of airway obstruction in COPD, anticholinergic agent became first-line treatment. Exacerbations of COPD are associated with progression of disease. Clinical trials have confirmed that tiotropium is superior to salmeterol in preventing COPD exacerbations in patients with moderate to very severe COPD with history of exacerbations. Tiotropium also resulted in a significant reduction in the decline in post-bronchodilator FEV1, suggesting possible disease modification in younger patients with COPD. The safety data review does not indicate an increased risk for death or cardiovascular morbidity during tiotropium treatment in patients with COPD. Tiotropium was associated with a reduction in the risk of all-cause mortality. PMID- 22299533 TI - [Evaluation of the effectiveness of treatment for patients with COPD]. AB - Objectification assess the health status of COPD patients poses numerous problems arising from the complexity of both the disease and medical co-operation with the patient. So far, the methods adopted do not correlate with the quality of life. Also, the discrepancy in the evaluation of their symptoms by patients leads to an underestimation of obtained information. Recently proposed a test study of COPD has been validated in many countries and can be implemented into daily practice. PMID- 22299534 TI - [Advances in the etiopathogenesis, diagnosis and treatment of paragangliomas]. AB - Paragangliomas are rare, benign or less frequently malignant tumors developing from cells of the paraganglia, a diffuse neuroendocrine system dispersed from skull base to the pelvic floor. Although paragangliomas may arise in any portion of this system, they most commonly occur below the diaphragm. Even 50% of the tumors may be hereditary and therefore genetic testing should be taken into consideration in all patients with paragangliomas. In many patients their presence leads to headaches, palpitations, sweating, or hypertension. However, subjects with nonfunctional tumors are either asymptomatic at presentation or experience only local symptoms caused by the mass effect. Functional paragangliomas can be almost always revealed by measurements of plasma concentrations of free metanephrines or 24-hour urinary outputs of fractionated metanephrines and catecholamines. There are also several morphological and functional imaging methods available that help localize neoplasm and assess its extent. In this paper, we discuss the published literature on the etiopathogenesis, diagnostic work up and the different treatment options for patients with paraganglioma. This review looks also at the recent advances in the physiology and molecular basis of these tumors. PMID- 22299535 TI - [Etiopathogenesis of atopic dermatitis]. AB - Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disease, pathogenesis of which has not been fully recognised yet. Th1/ Th2 cells dysregulation, skin barrier defects and influence of environmental factors, including allergens and microbes seem to play an important role in the disease. Apart from infiltration from the inflammatory cells, the histological picture of skin lesions occurring in the course of the disease shows some oedema as well as the reparative processes appearing as fibrosis and angiogenesis which points to participation of factors contributing to endothelial permeability and the growth in pathomechanism of the disease. The vascular endothelial growth factor - VEGF, is a multifunctional proinflammatory cytokine which, 50 000 times stronger than histamine, increases the vascular endothelial permeability and plays the major role in angiogenesis. The role of such cytokine in the acute and chronic inflammatory response has been poorly recognised. Overproduction of VEGF in the skin and release into the bloodstream of patients suffering from AD has been pointed to, which suggest some role of this cytokine in the pathomechanism of AD. PMID- 22299536 TI - [Reactive oxygen and nitrogen species]. AB - Reactive oxygen and nitrogen species (ROS and RNS respectively) play an important role in the proper functioning of many cellular processes. Generation of reactive oxygen species is an integral part of aerobic metabolism of cells. Their overproduction and subsequent oxidative stress occurs during pathogenesis of many diseases. Nitrosative stress is very closely linked to oxidative stress. Nitric oxide (NO), can react with molecular oxygen, superoxide anions and metal cations generating consecutive reactive oxygen species. These highly reactive chemical compounds react with proteins impairing their function by oxidation, or nitrosylation of amino acid residues, which may induce apoptosis. Furthermore, nitric oxide enhances the effect induced by cyclooxygenases and becomes a mediator of the inflammatory response. This paper gathers key information on the reactive oxygen and nitrogen species as well as processes in which they participate. PMID- 22299537 TI - [Spuriously unhealthy animal fats]. AB - Animal fats are generally considered as a source of saturated fatty acids and cholesterol, identified with arteriosclerosis and its clinical complications (cardiovascular diseases with heart attack, stroke, cerebral claudication). The real reason of arteriosclerosis are inflammation states of blood vessel endothelium caused by oxidative stress, hiperhomocysteinemia, hipertrigliceridemia, presence of artificial trans isomers and excess of eicosanoids originated from poliunsaturated fatty acids n-6. Present status of science proves that both saturated fatty acids and cholesterol present in animal food can not cause inflammation state. Moreover, animal fats are source of antioxidants active both in food and in human organism. Due to high oxidative stability animal fats do not make threat to human health. Milk fat, though high content of saturated fatty acids and cholesterol, possesses comprehensive pro health activity--against arteriosclerosis and cancerogenesis. PMID- 22299538 TI - [Historical background to the development of the concept of the borderline personality]. AB - The history of the development of the concept of borderline personality disorder dates back to the late nineteenth century when in 1884 described the first cases of patients with a clinical picture similar to today's concept of borderline personality disorder, using the first time the concept of borderline. On the current understanding of the borderline personality disorder had a significant impact available and valid diagnostic criteria included in the classifications ICD-10 and DSM-IV-TR and psychological theories such as psychoanalytic theory of "object relations" and cognitive behavioral approaches. PMID- 22299539 TI - Using insourcing to strengthen revenue cycle performance. PMID- 22299540 TI - The Affordable Care Act's impact on hospitals. PMID- 22299541 TI - Leveraging EDI files to improve your revenue cycle. PMID- 22299542 TI - Ocular injuries and severe ocular surface diseases in Malaysia. PMID- 22299543 TI - Looking beyond a seven billion population -- excitement or trepidations? PMID- 22299544 TI - Influence of a targeted educational intervention on evidence-based practice in two Malaysian maternity units: the SEA ORCHID project in Malaysia. AB - We conducted a before and after study to determine whether an educational intervention to build capacity in the understanding and implementation of evidence could result in improved outcomes for mothers and babies in obstetric and neonatal units of two Malaysian hospitals. Twelve practices and thirteen associated outcomes were selected based on clear evidence from the Cochrane Library. There were significant improvements in most practices with little change in outcomes. In the short term a targeted intervention to build capacity in the understanding and implementation of evidence results in an improved process of care without adverse outcomes. PMID- 22299545 TI - Optimisation of laboratory procedures for isolating human peripheral blood derived neutrophils. AB - Functional analysis of neutrophils requires isolation of these cells in the laboratory. Current isolation procedures are time consuming and can potentially activate the resting neutrophils. Thus, in this present study, we have optimised an existing laboratory protocol for human neutrophil isolation from peripheral blood. Twenty ml of blood samples were subjected to optimised density gradient separation and dextran sedimentation to obtain a pure population of neutrophils. The efficacy of the optimised manual post isolation of neutrophils was compared with pre isolation count performed by an automated haematology analyzer. The recovery of neutrophils via our optimised methods was 65.5% in comparison with neutrophils counts at pre-isolation. The morphological analysis of isolated neutrophils indicated the purity level more than 95% using Leishman staining. Our optimised laboratory procedures for neutrophils isolation successfully harvested neutrophils with good viability, purity and post recovery yield. This procedure provides an ideal platform to separate neutrophils for in vitro studies. PMID- 22299546 TI - Corneal endothelial cell density and morphology in normal Malay eyes. AB - This study was conducted to describe corneal endothelial cell density and morphology in Malay eyes. Non-contact specular microscopy was performed in 125 eyes of 125 Malay volunteers, aged 20-87 years. Studied parameters included endothelial cell density (CD), mean cell area (MCA), coefficient of variation (CV) in cell area, as well as hexagonal appearance of the cells. Mean endothelial cell density in the study population was 2648 +/- 310 cell/mm(2). Mean CA, CV and percentage of hexagonal cells were 382.8 +/- 47.7microm(2), 58.1 +/- 22.6, 44.3% +/- 11.5% respectively. There was a statistically significant decrease in endothelial cell density (correlation - 0.300, P = 0.001) and CV in cell size (correlation - 0.208, P = 0.02) with age. There was a statistically significant increase in mean cell area (correlation 0.300, P = 0.001) with increasing age. The correlation between age and percentage of hexagonal cells was insignificant (correlation 0.074, P = 0.41). In conclusion, a consistent decrease was noted in the endothelial cell density with increasing age. The differences in endothelial cell density between genders were statistically insignificant. PMID- 22299547 TI - Comparison between LMA-Classic and AMBU AuraOnce laryngeal mask airway in patients undergoing elective general anaesthesia with positive pressure ventilation. AB - BACKGROUND: The LMA-Classic laryngeal mask airway (Classic LMA) is an autoclavable and reusable laryngeal mask airway with strong evidence supporting its efficacy and safety. Due to the concern of infection risk particularly of prion disease, various single-use laryngeal mask devices were developed. The Ambu AuraOnce LMA (Ambu LMA) is a single use disposable laryngeal mask airway with special design that conforms better to the anatomy of the airway. OBJECTIVES: The Ambu LMA was compared to the LMA-Classic Classic LMA in respect to ease of insertion, adequacy of seal intraoperatively and postoperative complications in patients undergoing elective general anaesthesia with positive pressure ventilation. METHODS: One hundred and eighteen ASA I and II patients undergoing elective general anaesthesia were randomly allocated into receiving either the Ambu LMA or the Classic LMA. The time taken and number of attempts taken to insert the laryngeal mask was recorded. Intra-operative adequacy of seal was assessed via the amount of nitrous oxide leak using a nitrous oxide analyser. Readings were charted at 0, 20, 40 and 60 minutes of operation. Complications postoperatively (blood stains on the device and occurrence of sore throat) were also recorded. RESULTS: The success of first attempt insertion was comparable between the two groups (Classic LMA 87% versus Ambu LMA 83%). However the time of insertion was significantly shorter in the Ambu LMA group (p = 0.008). Nitrous oxide level was comparable between the two groups up to 20 minutes of operation. At 40 and 60 minutes, the Ambu LMA showed a significant lower nitrous oxide leak compared to the Classic LMA. Postoperatively, incidence of blood stains was comparable between the two groups, however the incidence of sore throat was lower in the Ambu LMA group (p = 0.025). CONCLUSIONS: This study demonstrated that the Ambu LMA was comparable to the Classic LMA in terms of the ease of insertion, but provided better seal during positive pressure ventilation with less postoperative sore throat. PMID- 22299548 TI - Insulin pump therapy in children and adolescents with Type 1 Diabetes: improvements in glycemic control and patients' satisfaction -- Hospital UKM experience. AB - Hospital UKM (Universiti Kebangsaan Malaysia) introduced the use of insulin pump therapy in children and adolescents with Type 1 Diabetes in Malaysia in April 2004. This study aims to evaluate the effectiveness of pump therapy and its impact on metabolic control among patients from our institution. Insulin pump therapy resulted in sustainable improvement in glycemic control throughout the six years of treatment with reduction in HbA1c in the first two years of pump use was statistically significant. The BMI SDS showed an increase trend but the changes before and after pump use was insignificant. There is also high level of treatment satisfaction reported among our insulin pump patients. PMID- 22299549 TI - Estimation of glomerular filtration rate using serum cystatin C in overweight and obese subjects. AB - BACKGROUND: Obesity and overweight are strong independent risk factors for chronic kidney disease (CKD). Using serum creatinine-based estimated glomerular filtration rate (eGFR) equations in these subjects may be inaccurate. On the other hand, cystatin C-based eGFR equations may overestimate CKD prevalence as recent findings suggest an association of cystatin C with obesity. The objective of this study was to assess the accuracy of a cystatin C-based eGFR equation compared to two creatinine -based eGFR equations in overweight and obese subjects. METHODS: This was a prospective cross-sectional study which recruited healthy volunteers aged 18-55 years with a body mass index (BMI) > or = 23kg/m(2) (Asia Pacific Guidelines). Their renal profiles, serum cystatin C and 99m technetium diethylene triamine pentacetic acid (99)mTc-DTPA) scans were performed on the same day. The correlations and accuracy of the creatinine-based and cystatin C-based eGFR equations with the (99)mTc-DTPA GFR were determined. RESULTS: One hundred and one subjects with a median age of 30.0 (27.0-43.5) years and mean BMI of 28.7 +/- 4.5 kg/m(2) were recruited. The cystatin C-based eGFR equation showed the best correlation with the (99)mTc-DTPA GFR (r = 0.526, p = 0.001) and was more accurate in measuring abnormal GFR compared to the creatinine based eGFR equations. CONCLUSION: Our study showed that the cystatin C-based eGFR equation was more accurate, sensitive and specific in overweight and obese subjects compared to the creatinine-based eGFR equations. PMID- 22299550 TI - Differences in patient profiles of abdominal and pulmonary tuberculosis: a comparative study. AB - OBJECTIVES: Tuberculosis remains a common infection and is often associated with non-specific constitutional symptoms or laboratory investigations regardless of site of manifestations. This study compares the profiles of abdominal tuberculosis (ATB) and pulmonary tuberculosis (PTB). METHODS: Patients with ATB (n=34, male-21, mean age 43.3 +/- 16.0 years) diagnosed over a nine year period were identified from the National Tuberculosis registry and retrospectively reviewed. Comparisons were made with patients treated for PTB (n=163). RESULTS: The most commonly affected sites were the ileocecal regions, peritoneum and hepatobiliary system. Common clinical presentations were abdominal pain (61.8%), anorexia (44.1%), weight loss (55.9%), fever (41.1%) and abdominal distension (29.4%). Four patients had concomitant active PTB. Compared to PTB, patients with ATB had significantly lower serum haemoglobin (11.6 +/- 2.4 vs. 12.6 +/- 2.0 gm/dL, p=0.036) and higher rate of adverse events of antituberculous treatment (50% vs. 15.4%, p < 0.001). There were no difference in prevalence of constitutional symptoms (fever, weight loss and anorexia), platelet level, albumin, total protein and erythrocyte sedimentation rate. Importantly, there was no difference in the treatment response. More patients with ATB and concomitant active PTB had reported weight loss (100% versus 36.7%, p = 0.017). CONCLUSION: There are differences in the profiles of ATB and PTB. Awareness of such differences can help to improve the understanding and management of this infection. PMID- 22299551 TI - Patterns of differentiated thyroid cancer in Baluchistan Province of Pakistan: some initial observations. AB - The incidence of thyroid cancer is increasing in several countries. The main objective of this retrospective study was to find and describe province-specific estimates of incidence in males and females by age groups for differentiated thyroid cancer (DTC). This study reports on 87 cases of DTC from Baluchistan province of Pakistan treated with post operative radioiodine at the Center for Nuclear Medicine and Radiotherapy (CENAR) Quetta from January 2003 to December 2009. The patient data has been collected from CENAR Quetta. Patients with DTC were confirmed by clinical examination, thyroid scintigraphy (Thyroid scan), blood tests (T3, T4, TSH) and histopathalogy tests and then treated with radioiodine. The Median age of the patients was 35.5 years (Range 12-70 years). The final histological diagnosis was papillary carcinoma in 71 (81.6 %) cases, follicular carcinoma in 6 (6.9%) cases while 10 (11.5%) cases presented with mixed papillary and follicular carcinoma. About 53 % cases were found in females with age 21-40 years. No strike predominance was observed in any age group for males. Four patients presented with recurrence while six patients showed metastasis in cervical lymph nodes. The small annual incidence did not follow any definite pattern. DTC has a small incidence in Baluchistan due to lack of education and health care facilities. The incidence of DTC is higher in females when compared with males as per this study. This preliminary study will provide an insight to incidence of DTC, its treatment facilities and future planning strategies in Baluchistan, Pakistan. PMID- 22299552 TI - Thalassaemia: a study on the perception of patients and family members. AB - Marked improvement in the management of thalassaemia has not been matched by progress in psychosocial rehabilitation as thalassaemia continues to pose challenges to patients and their family members. Few studies have been carried out in Malaysia to look at such issues. This study is therefore to explore the concerns, beliefs and feelings about thalassaemia. It was conducted in the year 2009 over 7 months on "focus groups", in patients aged 8-22 years and parents attending Paediatric Clinic of Tengku Ampuan Afzan Hospital, Kuantan, Pahang. Results showed that concerns and adverse impact were related to lower grades in education, poor self-image, less chance of employment, marriage, financial burden and social integration. Compliance to subcutaneous iron chelator was poor. There were various concerns related to blood transfusion therapy. It is evident that thalassaemia greatly affects the psychosocial dimensions and a more structured long term psychosocial support is needed to improve quality of life of patients. PMID- 22299553 TI - Characterization and safety assessment of bioengineered limbal epithelium. AB - Transplantation of cultivated limbal epithelium on substrates such as amniotic membrane is an established treatment for severe ocular surface disease with limbal stem cell deficiency. In this study, we adapted an established method to generate sheets of limbal epithelium on amniotic membrane and characterized the cells contained in these sheets and tested them for safety with regard to microbial contamination. Human limbal biopsies were cultivated on denuded amniotic membranes. After three weeks of culture, the phenotypes of cultivated cells were analyzed by immunohistochemistry and real-time RT-PCR for the expression of a panel of specific markers. Cultivated limbal epithelial cell sheets were also analyzed by scanning (SEM) and transmission (TEM) electron microscopy. Sterility tests and mycoplasma assays were conducted for the safety of product. A confluent layer of polygonal cells was formed in 2 weeks and 1-3 stratified layer of cells were observed after three weeks of culture. Cultivated cells were positive for p63, K3, K19, and involucrin but negative for K14, integrin alpha9 and ABCG2 when analyzed by immunohistochemistry. Expression of molecular markers was detectable with real-time RT-PCR. SEM showed multilayer of flat squamous polygonal epithelial cells. Desmosomal and hemidesmosomal attachments were evident. Our study showed that cultivated limbal epithelium consists of limbal progenitors as well as differentiated corneal epithelial cells. SEM and TEM analysis showed cultivated cells demonstrated typical features of corneal epithelium. The risk of contamination is low and can be prevented by culturing the cells in a clean room facility complying to Good Manufacturing Practice standard. PMID- 22299554 TI - Effectiveness of fresh frozen plasma as supplementary treatment in organophosphate poisoning. AB - With the establishment of the inadequate efficiency of atropines and oximes in reducing morbidity and mortality of patients poisoned by organophosphates, more attention is given to using other methods such as Fresh Frozen Plasma (FFP) as a bioscavenger to mop up organophosphate toxins. This randomized clinical trial was conducted on 56 organophosphate poisoned patients who were randomly assigned to the FFP and control groups in order of admission. The routine treatment in both groups included atropine and, in moderate to severe cases of poisoning, pralidoxime. The FFP group received four packs of FFP as stat dose at the beginning of treatment. No significant difference was seen between the two groups on the atropine and pralidoxime dosage, hospitalization length and mortality. The present study showed that using four packs of FFP as stat dose at the onset of treatment had no significant effect on the clinical course of organophosphate poisoned patients. PMID- 22299555 TI - LINAC based radiosurgery and radiotherapy for neurosurgical diseases: what have we learnt so far. AB - BACKGROUND: Stereotactic radiosurgery uses a single fraction high dose radiation while stereotactic radiotherapy uses multifractionated lower dose focused radiation. MATERIALS AND METHODS: Radiosurgery used rigid CRW head frame while stereotactic radiotherapy utilized GTC or HNL relocatable frames. Stereotactic planning and radiation involved Radionics X-plan and LINAC system. RESULTS: Since December 2001, we have treated 83 lesions from 77 patients using either radiosurgery or fractionated stereotactic radiotherapy. Eighty six percent (86%) of our treated lesions showed favourable outcomes with median follow-up of 32 months (0-7 years). CONCLUSIONS: Our lessons from LINAC precision radiation therapy uphold its value as a promising and effective tool in treating a range of nervous system pathologies. PMID- 22299556 TI - Awareness of diastolic heart failure as a disease entity among Malaysian doctors - a questionnaire survey from three general hospitals. AB - The concept of diastolic heart failure (DHF) is not new. However awareness and understanding on this subject may remains uncertain among medical practitioners. We wished to examine the extent of awareness of such entity among doctors in Malaysia. A questionnaire was designed and distributed randomly during hospital Continuous Professional Development (CPD/CME) sessions and also in the respective outpatient departments (OPD) between July to October 2008. This cross-sectional survey in three urban-based general hospitals showed that there are a significant proportion of doctors who are lack of understanding and awareness of diastolic heart failure. PMID- 22299557 TI - Pet scan and gynaecological malignancies: Hospital Sultanah Bahiyah experience. AB - The objective of this study was to evaluate the role of PET/CT in diagnosing and evaluating patients with suspected gynaecological tumour recurrence and persistent disease following treatment. This cross-sectional study involving 26 patients with gynaecological malignancies was carried out at Hospital Sultanah Bahiyah between 2006 and 2008. The standard imaging modalities disclosed possible tumour recurrence or persistent disease in 24 of the 26 patients (92.3%). Two patients with negative CT were subjected to PET/CT due to persistently elevated serum tumour markers. PET/CT confirmed tumour recurrence in 9 (34.6%) patients and was inconclusive in 2 (7.7%) patients. No abnormal uptake was observed in 15 (57.7%) patients. Of the 9 patients with positive PET/CT, 7 (77.8%) had a repeat PET/CT and 2 (22.2%) had a CT following subsequent treatment which confirmed no further evidence of disease. Patients with negative or inconclusive PET/CT were either continued with routine follow-up or had a close monitoring by either CT or serum tumour markers. With the availability of PET/CT, almost two-third of patients did not have to undergo unnecessary chemotherapy or radiotherapy. Integrated PET/CT imaging offers beneficial effects in both diagnosing and evaluating suspected tumour recurrence and persistent disease in gynaecological malignancies. PMID- 22299558 TI - Globe avulsion secondary to maxillofacial trauma. AB - We report a case of globe avulsion secondary to maxillofacial trauma and propose potential mechanisms of injury. This case highlights the importance of wearing proper safety attire, especially during motorcycling. PMID- 22299559 TI - An unusual entry site of an intraorbital foreign body in a child. AB - Intraorbital foreign bodies (IOrbFB) are associated with both sight and life threatening injuries. We report a case of an IOrbFB associated with retrobulbar hemorrhage and injury of the frontal sinus in an 11 year-old boy, after history of fall from the tree. Imaging studies revealed a metallic foreign body (FB) in the orbit and fracture of the walls of the frontal sinus. The usual entry route of an IOrbFB is either through the eye or orbital walls and extremely rare through the paranasal sinuses. This is the first reported case of a FB entering the orbit through the frontal sinus. PMID- 22299560 TI - Pneumonectomy for congenital isolated unilateral pulmonary artery agenesis. AB - Unilateral pulmonary artery agenesis (UPAA) is a rare congenital anomaly usually diagnosed in infancy due to associated cardiovascular malformations. We report a rare case of isolated right UPAA that presented atypically in adulthood with massive haemoptysis requiring a pneumonectomy. This case highlights the importance of maintaining a high clinical suspicion, the role of CT angiography and a multi disciplinary approach. Optimal management is often surgical however bronchial artery embolization (BAE) remains a useful adjunct. PMID- 22299561 TI - Median occipital condyle associated with atlantoaxial instability and myelopathy: a case report. AB - A Median Occipital Condyle is a rare occurrence. We have not found any clinical studies in the literature and myelopathy due to a median condyle has been reported once before. Myelopathy due to anomalies of the craniovertebral junction is rare in neurosurgical practice. We describe a case of a 72-year-old man presenting with progressive myelopathy related to a median occipital condyle located at the anterior foramen magnum region. PMID- 22299562 TI - Adult Bochadalek hernia complicated with perforated gastric ulcer: preoperative diagnosis with multiplanar CT. PMID- 22299563 TI - Osteo-odonto-keratoprosthesis for end-stage cornea blindness. AB - We report the first case of Osteo-odonto-keratoprosthesis (OOKP) who successfully underwent surgery in Malaysia following a grade 4 (severe) chemical injury in both eyes in 2006. The patient's left eye was eviscerated and his right eye underwent penetrating keratoplasty. However, the corneal graft failed and became opaque. His right eye could only perceive light. The OOKP was offered to him hoping to recover some functional vision. He underwent a 2-stage surgery to implant the OOKP into his right eye. However, 2 months post-operation, he developed vitreous haemorrhage. A successful pars plana vitrectomy (PPV) was performed via the limited view through the lens. He attained a final visual acuity of 6/60 (N36). He was able to mobilize more independently, feed, dress himself and read large print. PMID- 22299564 TI - Complete paraparesis following resection of parasagittal meningioma: recovering function with an early intensive neurorehabilitation program. AB - Paraparesis can occur as a primary presentation of brain pathology at the motor strip along the parasagittal region. It could also occur as a neurological complication especially following resection of parasagittal meningioma with infiltration of the superior sagittal sinus (SSS). We report a case of a complete paraparesis immediately following resection of bilateral parasagittal meningioma with infiltration of the middle third of the SSS. A gradual improvement in neurological recovery and functional outcome was observed over a period of one year after undergoing an intensive neurorehabilitation program beginning from the acute inpatient phase post surgery. PMID- 22299565 TI - Surgery for isolated non-inflammatory chronic total occlusion of the left main coronary artery: a case report and literature review. AB - Chronic total occlusion (CTO) of the left main coronary artery (LMCA) is a rare manifestation of coronary artery disease (CAD) and defined by a total absence of antegrade blood flow to the left anterior descending (LAD) and circumflex (Cx) system. Patients are at high risk of myocardial ischaemia as a sizeable area of myocardium is at risk and thus require urgent intervention. Surgery is the treatment of choice especially with CTO lesions as percutaneous coronary intervention has limited success with a high restenosis rate. We report a rare case of a young Chinese male who presented acutely with a myocardial infarction and discuss the aetiology and peri-operative technical considerations for successful surgery with this condition. PMID- 22299566 TI - Rhinocerebral mucormycosis with isolated sixth nerve palsy in an immunocompetent patient. AB - We report a case of rhinocerebral mucormycosis in a 31 year old immunocompetent female presenting initially like acute rhinosinusitis with nasal stuffiness, severe headache, vomiting who soon developed isolated right lateral rectus palsy. Computed tomography (CT) scan of the Post-Nasal Spaces(PNS) showed an ill defined expansile heterogenous density mass in the sphenoid with extension into the ethmoids, nasal cavity, optic canal, superior orbital fissure, clivus and right temporal lobe with signal void in Magnetic Resonance Imaging (MRI). The debris and polypoid mucosa obtained on nasal endoscopy revealed mucormycosis on histopathologic examination. The patient was managed with urgent surgical debridement and medical management. PMID- 22299567 TI - Parapharyngeal space synovial sarcoma. AB - Synovial sarcoma is a rare soft tissue sarcoma that commonly involves the lower extremities and occurs predominantly in young adults. It very rarely occurs in the head and neck region and carries a poor prognosis. The tumor demonstrates both a loco-regional and a systemic pattern of spread that makes management challenging. Combined modality therapy of this aggressive tumor yields better results. Herein, we described a 58 years old lady presented with left parapharyngeal synovial sarcoma. This is to demonstrate the aggressiveness of the disease despite complete surgical excision followed by post operative radiotherapy. Local regional control was difficult and recurrence of disease was seen in this particular patient. PMID- 22299568 TI - Hybrid procedure in pseudoaneurysm of the descending thoracic aorta in Hospital Kuala Lumpur. AB - Conventional open repair for Thoracoabdominal aortic aneurysm (TAA) is associated with high morbidity and mortality. Spinal cord ischemia (SCI), renal failure, bowel ischemia and mortality are established complications following this procedure. With the advent of endovascular stent technology, various novel approaches have been described to reduce these complications, namely fenestrated stent graft and hybrid procedure. We present a case of hybrid procedure in a pseudoaneurysm of descending thoracic aorta done in Kuala Lumpur Hospital. PMID- 22299569 TI - Kaposi's sarcoma: case report and treatment options. AB - Kaposi's sarcoma (KS) is strongly associated with Human Herpes Virus 8 (HHV8) and Human Immunodeficiency Virus infection (HIV). It was the first malignancy to be linked with Acquired Immunodeficiency Syndrome (AIDS). We report a case of Kaposi's sarcoma in a newly diagnosed retroviral homosexual patient with CD4 count of 21. He had multiple firm discrete violaceous plaques and nodules scattered over the face, scalp, hard palate, trunk and genitalia. Biopsy of a skin nodule over the trunk and a biopsy of a lesion from the gastric mucosa confirmed Kaposi's sarcoma. He was started on Highly Active Antiretroviral Therapy (HAART) and cryotherapy (liquid nitrogen) was given for the lesions over the skin. He responded well to treatment. Liquid nitrogen is a useful adjuvant treatment for Kaposi's sarcoma. PMID- 22299570 TI - First female graduates in Malaya. PMID- 22299571 TI - Update on the management of peripheral arterial disease (PAD). AB - There has been much progress made in the management of peripheral arterial disease (PAD) in the past two decades. Progress in the understanding of the endothelial-platelet interaction during health and disease state have resulted in better antiplatelet drugs that can prevent platelet aggregation, activation and thrombosis during angioplasty and stenting. Collaborative effort by different international societies has resulted in a consensus guideline that recommends the modality of intervention in certain disease states. Progress in perioperative care has reduced the morbidity and mortality associated with peripheral vascular reconstruction surgery. Nevertheless, the advances in percutaneous peripheral intervention (PPI) have made a paradigm shift in the current management of patients. The procedure is safe and effective and is emerging as the first choice revascularization procedure. PMID- 22299572 TI - Graphene: corrosion-inhibiting coating. AB - We report the use of atomically thin layers of graphene as a protective coating that inhibits corrosion of underlying metals. Here, we employ electrochemical methods to study the corrosion inhibition of copper and nickel by either growing graphene on these metals, or by mechanically transferring multilayer graphene onto them. Cyclic voltammetry measurements reveal that the graphene coating effectively suppresses metal oxidation and oxygen reduction. Electrochemical impedance spectroscopy measurements suggest that while graphene itself is not damaged, the metal under it is corroded at cracks in the graphene film. Finally, we use Tafel analysis to quantify the corrosion rates of samples with and without graphene coatings. These results indicate that copper films coated with graphene grown via chemical vapor deposition are corroded 7 times slower in an aerated Na(2)SO(4) solution as compared to the corrosion rate of bare copper. Tafel analysis reveals that nickel with a multilayer graphene film grown on it corrodes 20 times slower while nickel surfaces coated with four layers of mechanically transferred graphene corrode 4 times slower than bare nickel. These findings establish graphene as the thinnest known corrosion-protecting coating. PMID- 22299573 TI - Photophysical and redox properties of perylene bis- and tris-dicarboximide fluorophores with triplet state formation: transient absorption and singlet oxygen sensitization. AB - A detailed photophysical characterization of a couple of new perylene imide derivatives, a carboxylic trisimide PIx, and an asymmetrically substituted carboxylic bisimide PIa is presented. PIx and PIa have the lowest singlet excited state just below 2.6 eV. The dyes are remarkably fluorescent (phi(f) = 0.37 +/- 0.03 for PIa and phi(f) = 0.58 +/- 0.04 for PIx in toluene), but they also display an efficient intersystem crossing. This leads to typical excited triplet photophysics/photochemistry, with intense triplet state absorption spectra and efficient singlet oxygen ((1)Delta(g)) photosensitization (phi(Delta) = 0.68 +/- 0.02 for PIa and 0.44 +/- 0.02 for PIx in toluene). On the basis of the measured phi(Delta), a phi(isc) of 0.65 +/- 0.02 for PIa and 0.43 +/- 0.02 for PIx in toluene is derived. PIx reduces at -0.58 eV vs SCE, almost similarly to the corresponding symmetrically substituted perylene bisimide PI0, but unlike the latter, it has the first oxidation potential above +1.9 V. PIa is more electron rich and displays a more difficult first reduction at -0.95 V with a more facile oxidation at +1.75 V, similar to that of the parent PI0. The absorption spectra of the excited singlet and triplet states and that of electrochemically generated monoanions are reported. PMID- 22299574 TI - A pragmatic approach using first-principle methods to address site of metabolism with implications for reactive metabolite formation. AB - A majority of xenobiotics are metabolized by cytochrome P450 (CYP) enzymes. The discovery of drug candidates with low propensity to form reactive metabolites and low clearance can be facilitated by understanding CYP-mediated xenobiotic metabolism. Being able to predict the sites where reactive metabolites form is beneficial in drug design to produce drug candidates free of reactive metabolite issues. Herein, we report a pragmatic protocol using first-principle density functional theory (DFT) calculations for predicting sites of epoxidation and hydroxylation of aromatic substrates mediated by CYP. The method is based on the relative stabilities of the CYP-substrate intermediates or the substrate epoxides. Consequently, it concerns mainly the electronic reactivity of the substrates. Comparing to the experimental findings, the presented protocol gave excellent first-ranked epoxidation site predictions of 83%, and when the test was extended to CYP-mediated sites of aromatic hydroxylation, satisfactory results were also obtained (73%). This indicates that our assumptions are valid and also implies that the intrinsic reactivities of the substrates are in general more important than their binding poses in proteins, although the protocol may benefit from the addition of docking information. PMID- 22299575 TI - Inhibition of acetylpolyamine and spermine oxidases by the polyamine analogue chlorhexidine. AB - Acetylpolyamine and spermine oxidases are involved in the catabolism of polyamines. The discovery of selective inhibitors of these enzymes represents an important tool for the development of novel anti-neoplastic drugs. Here, a comparative study on acetylpolyamine and spermine oxidases inhibition by the polyamine analogue chlorhexidine is reported. Chlorhexidine is an antiseptic diamide, commonly used as a bactericidal and bacteriostatic agent. Docking simulations indicate that chlorhexidine binding to these enzymes is compatible with the stereochemical properties of both acetylpolyamine oxidase and spermine oxidase active sites. In fact, chlorhexidine is predicted to establish several polar and hydrophobic interactions with the active site residues of both enzymes, with binding energy values ranging from -7.6 to -10.6 kcal/mol. In agreement with this hypothesis, inhibition studies indicate that chlorhexidine behaves as a strong competitive inhibitor of both enzymes, values of Ki being 0.10 MUM and 0.55 MUM for acetylpolyamine oxidase and spermine oxidase, respectively. PMID- 22299576 TI - Metronidazole-coumarin conjugates and 3-cyano-7-hydroxy-coumarin act as isoform selective carbonic anhydrase inhibitors. AB - Reaction of 6-/7-hydroxycoumarin with metronidazole afforded conjugates which incorporate two interesting chemotypes which may inhibit carbonic anhydrases (CAs, EC 4.2.1.1) due to the presence of the coumarin moiety and possess radiosensitizing effects due to the presence of the nitroazole. Another dual action compound, which may act both as CA inhibitor as well as monocarboxylate transporter inhibitor, is 3-cyano-7-hydroxy-coumarin. These compounds have been investigated as inhibitors of 11 human CA isoforms. Submicromolar inhibition was observed against hCA VA, hCA VB, hCA VI, hCA VII, hCA IX, hCA XII and hCA XIV, whereas isoforms hCA I, II and XIII were not inhibited by these compounds. These coumarins thus act as isoform-selective CA inhibitors with the possibility to target isoforms involved in pathologies such as obesity (CA VA/VB) or cancer (CA IX and XII) without inhibiting the physiologically dominant, highly abundant hCA I and II. PMID- 22299577 TI - Three new aromatic sulfonamide inhibitors of carbonic anhydrases I, II, IV and XII. AB - 4-Sulfamoyl-N-(3-morpholinopropyl)benzamide (I-1), N-(3-morpholinopropyl)benzene 1,4-disulfonamide (I-2) and N-(4-diethylaminoethoxybenzyl)benzene-1,4 bis(sulfonamide (I-3), were prepared and assayed as inhibitors of four carbonic anhydrase (CA) isoenzymes hCA I, hCA II, hCA IV and hCA XII. These compounds exhibited nanomolar half maximal inhibitory concentration (IC(50)) ranging from 58 to 740 nmol/L. All three aromatic sulfonamides show different activities for the isoenzymes studied with lowest affinity against isoenzyme hCA XII. PMID- 22299578 TI - Inhibition of the alpha- and beta-carbonic anhydrases from the gastric pathogen Helycobacter pylori with anions. AB - The gastric pathogen Helicobacter pylori encodes two carbonic anhydrases (CAs, EC 4.2.1.1), an alpha- and a beta-class one, hpalphaCA and hpbetaCA, crucial for its survival in the acidic environment from the stomach. Sulfonamides, strong inhibitors of these enzymes, block the growth of the pathogen, in vitro and in vivo. Here we report the inhibition of the two H. pylori CAs with inorganic and complex anions and other molecules interacting with zinc proteins. hpalphaCA was inhibited in the low micromolar range by diethyldithiocarbamate, sulfamide, sulfamic acid, phenylboronic acid, and in the submillimolar one by cyanide, cyanate, hydrogen sulfide, divanadate, tellurate, perruthenate, selenocyanide, trithiocarbonate, iminodisulfonate. hpbetaCA generally showed a stronger inhibition with most of these anions, with several low micromolar and many submillimolar inhibitors detected. These inhibitors may be used as leads for developing anti-H. pylori agents with a diverse mechanism of action compared to clinically used antibiotics. PMID- 22299579 TI - Evaluation of a dithiocarbamate derivative as an inhibitor of human glutaredoxin 1. AB - CONTEXT: Glutaredoxins (GRX) are involved in the regulation of thiol redox state. GRX-1 is a cytosolic enzyme responsible for the catalysis of deglutathionylation of proteins. To date, very few inhibitors of GRX-1 have been reported. OBJECTIVE: The objective of this paper is to report 2-acetylamino-3-[4-(2-acetylamino-2 carboxyethyl-sulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl]propionic acid (2-AAPA) as an inhibitor of human GRX-1. MATERIALS AND METHODS: The mechanism of inhibition of GRX-1 was investigated using dialysis, substrate protection, and mass spectrometry. RESULTS: 2-AAPA inhibits GRX-1 in a time and concentration dependent manner. The activity did not return following dialysis indicating that inhibition is irreversible. Results of substrate protection and mass spectrometry indicate that the inhibition is occurring at the active site. The compound also produced GRX inhibition in human ovarian cancer cells. DISCUSSION: 2-AAPA is an irreversible GRX-1 inhibitor with similar or greater potency compared to previously reported inhibitors. CONCLUSION: The inhibition of GRX-1 by 2-AAPA could be used as a tool to study thiol redox state. PMID- 22299580 TI - Synthesis and biological evaluation of some thiazole derivatives as new cholinesterase inhibitors. AB - In the present study, some thiazole derivatives were synthesized via the ring closure reaction of 1-[2-(2-oxobenzo[d]thiazol-3(2H)-yl)acetyl]thiosemicarbazide with various phenacyl bromides. The chemical structures of the compounds were elucidated by (1)H NMR, (13)C NMR and mass spectral data and elemental analyses. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) using a modification of Ellman's spectrophotometric method. The compounds were also investigated for their cytotoxic properties using MTT assay. The most potent AChE inhibitor was found as compound 4e (IC(50) = 25.5 +/- 2.12 ug/mL) followed by compounds 4i (IC(50) = 38.50 +/- 2.12 ug/mL), 4c (IC(50) = 58.42 +/- 3.14 ug/mL) and 4g (IC(50) = 68 +/- 2.12 ug/mL) when compared with eserine (IC(50) = 0.025 +/- 0.01 ug/mL). Effective compounds on AChE exhibited weak inhibition on BuChE (IC(50) > 80 ug/mL). MTT assay indicated that the cytotoxic dose (IC(50) = 71.67 +/- 7.63 ug/mL) of compound 4e was higher than its effective dose. PMID- 22299581 TI - Modulation of expression of SOD isoenzymes in mud crab (Scylla serrata): effects of inhibitors, salinity and season. AB - Presence of several isoenzymes of superoxide dismutase (SOD) were demonstrated in tissues (abdominal muscle: 7 number, hepatopancreas: 13 number and gills: 7 number) of mud crabs (Scylla serrata) by employing specific staining of the enzyme in native-PAGE. SOD isoenzymes in tissues of mud crab were found to be thermolabile. The intensity of a major SOD band in tissues of crabs was reduced by the treatment of H(2)O(2) or chloroform:ethanol. KCN treatment resulted in splitting of that major SOD band into two or more distinct bands. SDS treatment resulted in disruption of SOD bands. A sex-specific SOD isoenzyme band of higher molecular weight was observed in gills and muscle in winter and summer seasons, respectively. The observed different SOD isoenzyme pattern in tissues at altered salinities and seasons suggests separate tissue-specific antioxidant adaptation strategies of crabs against abiotic factors. PMID- 22299582 TI - Cytotoxicity and DNA interactions of some platinum(II) complexes with substituted benzimidazole ligands. AB - In the present study, four Pt(II) complexes with 2-ethyl (1)/or benzyl (2)/or p chlorobenzyl (3)/or 2-phenoxymethyl (4) benzimidazole carrier ligands were evaluated for their in vitro cytotoxic activities against the human HeLa cervix, oestrogen receptor-positive MCF-7 breast, and oestrogen receptor-negative MDA-MB 231 breast cancer cell lines. The plasmid DNA interactions and inhibition of the BamHI restriction enzyme activities of the complexes were also studied. Complex 3 was found to be more active than carboplatin for all examined cell lines and comparable with cisplatin, except for the HeLa cell line. PMID- 22299583 TI - Tripeptides with non-code amino acids as potential serine proteases inhibitors. AB - Eight peptides of the general H-D-Ser-AA-Arg-OH formula, where AA = phenylglycine, phenylalanine, homophenylalanine, cyclohexylglycine, cyclohexylalanine, homocyclohexylalanine, alpha-methylphenylalanine and 1 aminocyclohexyl carboxylic acid were obtained and tested for their effect on the amidolytic activities of urokinase, thrombin, trypsin, plasmin, t-PA and kallikrein. We tested the hemolytic activity of the peptides against porcine erythrocytes and the antitumor activity against the human breast cancer cells, standard MCF-7 and estrogen-independent MDA-MB-231. The most active compounds were H-D-Ser-Chg-Arg-OH towards thrombin and H-D-Ser-Phg-Arg-OH towards plasmin with K(i) value 5.02 MUM and 5.7 MUM, respectively. PMID- 22299584 TI - Tumour suppressor PTEN enhanced enzyme activity of GPx, SOD and catalase by suppression of PI3K/AKT pathway in non-small cell lung cancer cell lines. AB - Phosphates and tensin homologue deleted on chromosome 10 (PTEN) is a tumour suppressor gene which dephosphorilates phosphoinositol 3,4,5 triphosphates. Therefore PTEN can regulate PI3K/AKT pathway in cells. Because of promoter methylation or gene deletion, PTEN expression is commonly decreased or lost in non-small cell lung cancer (NSCLC) cell lines. Therefore, we hypothesized that PTEN could regulate the activity of superoxide dismutase (CuZnSOD), glutathione peroxidase (GPx) and catalase. We first recreated PTENwt, G129R and G129E expressions in lung cell lines, in which endogenous PTEN expression was not detected. Then, we showed that PTEN could suppress AKT activity by its lipid phosphatase domain. We then examined the effect of recreated PTEN expressions in NSCLC cells. While PTENwt expression caused enhanced activity of SOD, GPx and catalase in transfected cells lines, neither G129R nor G129E expression effected enzyme activities. These results suggest that PTEN can up-regulate SOD, GPx and catalase activity by inhibition of PI3K/AKT pathway in NSCLC cell lines. PMID- 22299585 TI - Analysis of saponins and phenolic compounds as inhibitors of alpha-carbonic anhydrase isoenzymes. AB - A series of phenolic and saponin type natural products such as quercetin, rutin, catechin, epicatechin, silymarin, trojanoside H, astragaloside IV, astragaloside VIII and astrasieversianin X, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). We here report inhibitory effects of these compounds against five alpha-CA isozymes (hCA I, hCA II, bCA III, hCA IV and hCA VI). Most of the phenolic and saponin type compounds inhibited the isoenzymes quite effectively at low micromolar K(I)-s ranging between 0.1 and 4 uM, whereas a few derivatives were ineffective (K(I)-s > 100 uM). The results were remarkable which might lead to design of novel CAIs with a diverse inhibition mechanism compared to sulfonamide/sulfamate inhibitors. PMID- 22299586 TI - Inhibitory effect of novel pyrazole carboxamide derivatives on human carbonic anhydrase enzyme. AB - The synthesis, characterization and biological evaluation of novel pyrazole carboxamide derivatives (2-9) are presented. (1)H and (13)C NMR have been used for the structure description, possible tautomeric structures determination and hydrogen bonding observation. FT-IR results have confirmed the synthesis of the pyrazole derivatives while thermal gravimetric analysis has confirmed thermal stability up to 300 degrees C. The melting temperatures are strongly dependent on their crystal structure as confirmed by differential scanning calorimetry and X ray diffraction measurements. Impacts of 2-9 as possible antiglaucoma agents were investigated on carbonic anhydrase I and II (CA-I and II) isozymes purified from human erythrocytes in vitro. Compounds 3 and 9 had the highest inhibitory effect while compounds 6 and 8 showed the lowest inhibition. PMID- 22299587 TI - Effect of the non-steroidal anti-inflammatory drugs on the acyl-CoA synthetase activity toward medium-chain, long-chain and polyunsaturated fatty acids in mitochondria of mouse liver and brain. AB - Effect of eleven non-steroidal anti-inflammatory drugs on the acyl-CoA synthetase activities toward octanoic, palmitic, arachidonic and docosahexaenoic acids was evaluated in mouse liver and brain mitochondria. The drugs tested were aspirin, salicylic acid, diflunisal, mefenamic acid, indomethacin, etodolac, ibuprofen, ketoprofen, naproxen, loxoprofen, flurbiprofen. In mouse liver mitochondria, diflunisal and mefenamic acid exhibited the inhibitory activities not only for octanoic acid (IC(50) = 78.7 and 64.7 uM) and but also for palmitic acid (IC(50) = 236.5 and 284.4 uM), respectively. Aspirin was an inhibitor for the activation of octanoic acid only (IC(50) = 411.0 uM). In the brain, mefenamic acid and diflunisal inhibited strongly palmitoyl-CoA formation (IC(50) = 57.3 and 114.0 uM), respectively. The activation of docosahexaenoic acid in brain was sensitive to inhibition by diflunisal and mefenamic acid compared with liver. PMID- 22299588 TI - Inhibition of the beta-class carbonic anhydrases from Mycobacterium tuberculosis with carboxylic acids. AB - The growth of Mycobacterium tuberculosis is strongly inhibited by weak acids although the mechanism by which these compounds act is not completely understood. A series of substituted benzoic acids, nipecotic acid, ortho- and para-coumaric acid, caffeic acid and ferulic acid were investigated as inhibitors of three beta class carbonic anhydrases (CAs, EC 4.2.1.1) from this pathogen, mtCA 1 (Rv1284), mtCA 2 (Rv3588c) and mtCA 3 (Rv3273). All three enzymes were inhibited with efficacies between the submicromolar to the micromolar one, depending on the scaffold present in the carboxylic acid. mtCA 3 was the isoform mostly inhibited by these compounds (K(I)s in the range of 0.11-0.97 uM); followed by mtCA 2 (K(I)s in the range of 0.59-8.10 uM), whereas against mtCA 1, these carboxylic acids showed inhibition constants in the range of 2.25-7.13 uM. This class of relatively underexplored beta-CA inhibitors warrant further in vivo studies, as they may have the potential for developing antimycobacterial agents with a diverse mechanism of action compared to the clinically used drugs for which many strains exhibit multi-drug or extensive multi-drug resistance. PMID- 22299589 TI - A phosphinine 2-carboxaldehyde. AB - The first phosphinine 2-carboxaldehyde was synthesized as shown and transformed into an alkene via a Wittig reaction without destruction of the phosphinine ring. PMID- 22299590 TI - Mutation analysis of the CFTR gene in 225 children: identification of five novel severe and seven reported severe mutations. AB - BACKGROUND: Cystic fibrosis (CF) is the most common inherited disorder in Caucasian populations, with more than 1400 cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. The type of mutations and their distributions varies widely between different countries and/or ethnic groups. METHODS: We characterized the mutations in the CFTR gene by single-strand conformation polymorphism followed by sequencing in CF patients. RESULTS: Twelve mutations were found in 79/225 (35.1%) patients. The most frequent mutations were F508 deletion (31.1%), p.R1162* (2.2%), p.M1T (0.8%), and S559N (0.8%). Five novel severe mutations (p.R80N11fs*11, p.R75G, p.Y577*, p.Y808Yfs*10, and p.I331*) and three reported mutations (p.C343*, p.Ile1000*, p.M469V) were detected. CONCLUSION: The protocol for identification of mutations in cases of CF in developing countries would have to include a different set of mutations than those reported from western countries. PMID- 22299591 TI - DNA repair gene XRCC3 T241M polymorphism and bladder cancer risk in a Chinese population. AB - The X-ray repair cross-complementing group 3 (XRCC3), one of the DNA repair genes, was suggested to play an imperative role in the development of carcinogenesis. The objective of this study was to evaluate the role of the XRCC3 T241M polymorphism in bladder cancer susceptibility in a Chinese population. We genotyped 150 bladder cancer cases and 150 healthy controls who had been frequency matched to cases by age and sex. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. A significant association was found between smoker and bladder cancer [odds ratio (OR)=1.97, 95% confidence interval (CI)=1.24-3.13, p=0.004]. The XRCC3 241MM genotype was more frequent in the bladder cancer group than in the healthy controls group (OR=3.22, 95% CI=1.14-9.11, p=0.03). There were no significant associations between any genotypes and the stage, grade, and histological type of bladder cancer. Our study suggested an increased risk role of XRCC3 241MM genotype in bladder cancer susceptibility in a Chinese population. PMID- 22299592 TI - Microporous zinc tris[(4-carboxyl)phenylduryl]amine framework with an unusual topological net for gas storage and separation. AB - By employment of a new tris[(4-carboxyl)phenylduryl]amine ligand to assembly with the Zn(2+) ion, a new topological net built from four coordinatively linked ths nets is first evidenced in the 2-fold-interpenetrating framework FIR-1, which shows potential applications in gas storage and separation. PMID- 22299593 TI - Hairy nevus spilus: a case series. AB - Nevus spilus, also known as speckled lentiginous nevus, is a nevoid disorder characterized by hyperpigmented macules or papules scattered over a background of tan pigmentation. Although nevus spilus is mainly of cosmetic concern, malignant melanoma may rarely develop in the lesions. Although classically not mentioned as a hairy nevus, a few reports in literature mention overlying hypertrichosis in lesions of nevus spilus. We hereby report four cases of nevus spilus without malignant change with overlying terminal hairs that arose mainly from the background pigmented area. PMID- 22299594 TI - Methylene blue photodynamic therapy in malignant melanoma decreases expression of proliferating cell nuclear antigen and heparanases. AB - BACKGROUND: Malignant melanoma (MM) is a very aggressive tumour. Although surgical excision of MM in the early stages has a very good prognosis, it often fails to completely inhibit tumour progression. Methylene blue photodynamic therapy (MB-PDT) is a technique that induces tissue damage by reactive oxygen species (ROS). AIM: To investigate the efficacy of and potential use of MB-PDT in restraining the aggressiveness of MM by analysing levels of proliferating cell nuclear antigen (PCNA) and heparanase (HPSE, a molecular marker of cell invasion) in a mouse model. METHODS: Expression of PCNA and two HPSE isoforms were analysed using immunohistochemistry (IHC) after MB-PDT in mice. Tumour volume and weight were also measured. RESULTS: Two treatments with MB-PDT promoted a decrease of 99% decrease in tumour volume and 75% in tumour weight compared with untreated mice (P < 0.05). Using IHC, a decrease in expression of 75% for PCNA and 95% for both HPSE isoforms (P < 0.05) was found. CONCLUSION: MB-PDT is a cheap and efficient method of decreasing MM volume and thus disease progression. This reduction is mediated by downregulation of PCNA and heparanases. PMID- 22299595 TI - Hematoporphyrin encapsulated PLGA microbubble for contrast enhanced ultrasound imaging and sonodynamic therapy. AB - The purpose of this study was to develop a sonosensitizer-loaded multi-functional ultrasound (US) contrast agent for both tumour therapy and imaging. The hematoporphyrin (HP)-encapsulated poly(lactic-co-glycolic acid) microbubbles (HP PLGA-MBs) were prepared and filled with perfluorocarbon gases. The enhancement of US imaging and its sonodynamically induced anti-tumour effect were evaluated by both in vitro and in vivo experiments. The HP-PLGA-MBs have a narrow size distribution and smooth surface with a mean diameter of 702.6 +/- 56.8 nm and HP encapsulation efficiency of 63.50 +/- 1.26% and drug-loading efficiency of 2.15 +/- 0.13%. The HP-PLGA-MBs could well enhance the ultrasound imaging both in vitro and in vivo. A significant anti-tumour effect was obtained by HP-PLGA-MBs mediated sonodynamic therapy. The tumour growth rate and the tumour proliferation index were the lowest in the HP-PLGA-MBs plus sonication group. And the tumour cell apoptotic index was the biggest in the HP-PLGA-MBs plus sonication group. In conclusion, a sonosensitizer-loaded multi-functional contrast agent was constructed and the feasibility was demonstrated, which might provide a novel strategy for tumour imaging and therapy. PMID- 22299596 TI - Exciton chirality method in vibrational circular dichroism. AB - The interaction of two IR chromophores yields a strong vibrational circular dichroism couplet whose sign reflects the absolute configuration of the molecule. We present a method to determine absolute configuration of a chiral molecule based on this couplet without need of theoretical calculation. Not only can this method analyze various molecules whose absolute configuration is difficult to determine by other spectroscopic methods, but also it can significantly enhance VCD signals. PMID- 22299597 TI - Pentosan polysulfate increases affinity between ADAMTS-5 and TIMP-3 through formation of an electrostatically driven trimolecular complex. AB - The semi-synthetic sulfated polysaccharide PPS (pentosan polysulfate) increases affinity between the aggrecan-degrading ADAMTSs (adamalysins with thrombospondin motifs) and their endogenous inhibitor, TIMP (tissue inhibitor of metalloproteinases)-3. In the present study we demonstrate that PPS mediates the formation of a high-affinity trimolecular complex with ADAMTS-5 and TIMP-3. A TIMP-3 mutant that lacks extracellular-matrix-binding ability was insensitive to this affinity increase, and truncated forms of ADAMTS-5 that lack the Sp (spacer) domain had reduced PPS-binding ability and sensitivity to the affinity increase. PPS molecules composed of 11 or more saccharide units were 100-fold more effective than those of eight saccharide units, indicating the involvement of extended or multiple protein-interaction sites. The formation of a high-affinity trimolecular complex was completely abolished in the presence of 0.4 M NaCl. These results suggest that PPS enhances the affinity between ADAMTS-5 and TIMP-3 by forming electrostatically driven trimolecular complexes under physiological conditions. PMID- 22299598 TI - Spinal arachnoiditis and cyst formation with subarachnoid haemorrhage. AB - We present the case of a 58-year-old lady with p-ANCA vasculitis who suffered a WFNS grade 1 subarachnoid haemorrhage (Fisher grade 1) secondary to a ruptured left posterior inferior cerebellar artery aneurysm and then developed a rare complication of radiologically progressive spinal arachnoiditis despite maintained clinical response to definitive treatment measures. PMID- 22299599 TI - Effect of the ethinylestradiol/levonorgestrel combined oral contraceptive on the activity of cytochrome P4503A in obese women. AB - AIM(S): While it is known that CYP3A4/5 activity is decreased with combined oral contraceptive (COC) use and obesity suppresses CYP expression, the combined effects of obesity and COC use on CYP3A4/5 activity are unclear. Therefore, our aim was to examine the effect of COC usage on CYP3A4/5 activity in obese women. METHODS: Thirty-four, obese (body mass index, BMI > 30 kg m(-2)) women of reproductive age (18-35 years old) were placed on a COC pill containing 20 ug ethinylestradiol/100 ug levonorgestrel for 21 days starting at the onset of menses. A midazolam pharmacokinetic study was conducted prior to initiation and after 21 days of COC treatment. Serial blood samples were collected and plasma concentrations of midazolam were measured using liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were estimated using a non-compartmental method. RESULTS: Midazolam clearance, a surrogate measure of CYP3A4/5 activity, was significantly decreased upon COC use (63.3 l h(-1) vs. 53.9 l h(-1), P < 0.05). A median decrease of 5.6 l h(-1) (95% CI -4.1, 13.3 l h(-1)) was observed. However, the magnitude of change was similar to that reported in women with normal BMI. CONCLUSIONS: Although we hypothesized that obesity might amplify the impact on CYP3A4/5 activity in COC users, we found that this was not the case. This finding is reassuring regarding potential additional drug-drug interactions in obese COC users as CYP3A4/5 is a major enzyme in the metabolism of many marketed drugs. PMID- 22299600 TI - Role of rapamycin-induced autophagy in pancreatic islets. PMID- 22299601 TI - Perspectives on immunomodulation early in life. AB - The immune system early in life is characterized by immature activation and function of immune cells and a preponderance of Th2 cytokines. Together with other factors such as genetics and epigenetics, these immature immune responses might prone newborns susceptible to severe infections as well as allergic diseases. Immunomodulation therapy may have potential as therapeutic strategy against those disorders and might have implication in early-life interventions in the future. In this review, we will focus on two immunomodulatory substance classes, Toll-like receptor (TLR) ligands and sphingolipids, which are the focus of extensive research to date. Both TLRs and sphingolipid receptors have a very distinct distribution pattern and function on immune cells. Therefore, they can potentially modulate and balance immune responses, which might be in particular beneficial for the immaturity of the immune response early in life. PMID- 22299602 TI - Adverse cardiovascular effects of anabolic steroids: pathophysiology imaging. AB - BACKGROUND: Anabolic-androgenic steroids (AAS) are widely abused for enhancing muscle mass, strength, growth and improving athletic performance. MATERIALS AND METHODS: In recent years, many observational and interventional studies have shown important adverse cardiovascular effects of AAS abuse. CONCLUSIONS: This review discusses established and future perspectives of novel molecular imaging techniques that may serve as potential tools for early detection of AAS associated cardiovascular disorders. PMID- 22299604 TI - Non-ionic amphiphilic homopolymers: synthesis, solution properties, and biochemical validation. AB - A novel type of nonionic amphipols for handling membrane proteins in detergent free aqueous solutions has been obtained through free-radical homo-telomerization of an acrylamide-based monomer comprising a C(11) alkyl chain and two glucose moieties, using a thiol as transfer reagent. By controlling the thiol/monomer ratio, the number-average molecular weight of the polymers was varied from 8 to 63 kDa. Homopolymeric nonionic amphipols were found to be highly soluble in water and to self-organize, within a large concentration range, into small, compact particles of ~6 nm diameter with a narrow size distribution, regardless of the molecular weight of the polymer. They proved able to trap and stabilize two test membrane proteins, bacteriorhodopsin from Halobium salinarum and the outer membrane protein X of Escherichia coli, under the form of small and well-defined complexes, whose size, composition, and shape were studied by aqueous size exclusion chromatography, analytical ultracentrifugation, and small-angle neutron scattering. As shown in a companion paper, nonionic amphipols can be used for membrane protein folding, cell-free synthesis, and solution NMR studies (Bazzacco et al. 2012, Biochemistry, DOI: 10.1021/bi201862v). PMID- 22299605 TI - Schizophrenia and personality disorder patients' adherence to music therapy. AB - BACKGROUND: Music therapy is used in psychiatric treatment of severe psychiatric conditions such as schizophrenia, depression and personality disorder. AIM: To investigate adherence and predictors for adherence to music therapy treatment in patients diagnosed with schizophrenia or personality disorder. METHOD: Demographic, psychiatric and therapeutic data were collected for 27 patients receiving music therapy treatment over a 1-year observation period and a 1-year follow-up period. Predictors for adherence to music therapeutic treatment were determined by means of regression analysis. RESULTS: Drop-out from treatment was low (11.5%) and none of the variables significantly predicted adherence. Lack of significance may be because of type 2 error. CONCLUSION: Patients with severe mental disorder may adhere to music therapy treatment. PMID- 22299606 TI - Primary immunodeficiency diseases in the Middle East. AB - Reports on primary immunodeficiency diseases (PIDs) have clearly shown wide geographic and ethnic variations. Understanding these variations is expected to play a major role in improving the diagnosis and management of such diseases, and will also affect research on PIDs. In this short review, we explore the unique aspects of primary immunodeficiencies in the Middle East. PMID- 22299607 TI - Neurologic adverse events following influenza A (H1N1) vaccinations in children. AB - BACKGROUND: Since the monovalent pandemic influenza A (H1N1) vaccine was recommended worldwide in October 2009, there has been a shortage of pediatric clinical data for post-vaccine neurologic adverse events (NAE), including Guillain-Barre syndrome. We reviewed pediatric NAE data following H1N1 vaccinations and for patients with peripheral neuropathy, we followed their progress. METHODS: In our single-center study, we retrospectively reviewed 14 cases of children who visited the Division of Pediatric Neurology in the Department of Pediatrics of Chonnam National University Hospital due to NAE following monovalent influenza A (H1N1) vaccination between November 2009 and March 2010. RESULTS: Clinical diagnoses for major NAE included: polyneuropathy in the extremities (11/14, 78.6%), sensory mononeuropathy with numbness in the left fibula area (1/14, 7.1%), Bell's palsy (1/14, 7.1%) and recent-onset acute headache only (1/14, 7.1%). Therefore, most patients were diagnosed as having peripheral neuropathy (13/14, 92.9%), and two met the Brighton Collaboration Guillain-Barre syndrome definition criteria for level 3 (the lowest level of diagnostic certainty). CONCLUSIONS: Post-vaccine NAE were mainly motor weakness due to polyneuropathy, which had a good prognosis of complete improvement within a few months without sequelae. PMID- 22299613 TI - [Suddenly appearing erythematous umbilical nodule with central gray-black color]. PMID- 22299615 TI - Incidence of visual impairment and blindness in indigenous Australians within Central Australia: the Central Australian Ocular Health Study. AB - BACKGROUND: To estimate the incidence and causes of visual impairment and blindness among indigenous Australians living in Central Australia. DESIGN: Clinic-based cohort study. PARTICIPANTS: A total of 1884 individuals aged >=20 years living in one of 30 remote communities within the statistical local area of 'Central Australia'. METHODS: From those initially recruited, 608 (32%) participants were reviewed again between 6 months and 3 years (median 2 years). Patients underwent Snellen visual acuity testing and subjective refraction. Following this, an assessment of their anterior and posterior segments was made. Baseline results were compared with those who were reviewed. MAIN OUTCOME MEASURES: The annual incidence rates and causes of bilateral visual impairment (vision worse than Snellen visual acuity 6/12 in the better eye) and bilateral blindness (Snellen visual acuity worse than 6/60 in the better eye). RESULTS: The annual incidence of bilateral visual impairment and blindness was 6.82% (8.12% for those aged >=40 years) per year and 0.50% (0.62% for those aged >=40 years) per year, respectively. Refractive error, followed by cataract and diabetic retinopathy, were the main causes for incident bilateral visual impairment and blindness. CONCLUSION: This study has demonstrated rates of incident bilateral blindness and visual impairment among the indigenous Australian population within Central Australia, which are substantially higher than those from the non-indigenous population. Services need to address the underlying causes of this incident vision loss to reduce visual morbidity in indigenous Australians living in central Australia. PMID- 22299617 TI - EPA and DHA differentially affect in vitro inflammatory cytokine release by peripheral blood mononuclear cells from Alzheimer's patients. AB - It has been hypothesized that pro-inflammatory cytokines may play a pathogenic role in Alzheimer's disease (AD), and that n-3 polyunsaturated fatty acids may be protective against the development and progression of this disease. A reduced release of inflammatory cytokines by lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) from AD patients dietary supplemented with a mixture of eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) was recently reported. On this basis, we investigated the possible differential effects of the two purified fatty acids on inflammatory cytokine release, a subject still not explored, even though of great pharmacological interest. We treated in vitro phytohaemagglutinin (PHA)- or LPS-stimulated PBMCs from AD patients and age-matched healthy controls (HCs) with purified EPA or DHA. Higher pro- to anti-inflammatory cytokine ratios, indicative of a pro-inflammatory profile, were observed in PHA-stimulated PBMCs from AD patients in basal conditions. The addition of both EPA and DHA markedly reduced the cytokine release, with DHA showing always a more prominent effect than EPA. However, whereas DHA reduced only the high IL-1beta/IL-10 ratio, EPA was able to reduce also the IL-6/IL-10 ratio. In stimulated PMBCs from HCs the reducing effect on cytokine release was not always observed, or observed at a lower degree. In conclusion, whereas DHA appeared more powerful in inhibiting each single inflammatory cytokine, the proinflammatory profile of the AD patients' cells was better reverted by EPA to a profile more similar to that found in HCs. A combination of both the fatty acids, seems to be still the best solution. PMID- 22299616 TI - Measurement of the plasma levels of antibodies against the polymorphic vaccine candidate apical membrane antigen 1 in a malaria-exposed population. AB - BACKGROUND: Establishing antibody correlates of protection against malaria in human field studies and clinical trials requires, amongst others, an accurate estimation of antibody levels. For polymorphic antigens such as apical membrane antigen 1 (AMA1), this may be confounded by the occurrence of a large number of allelic variants in nature. METHODS: To test this hypothesis, plasma antibody levels in an age-stratified cohort of naturally exposed children from a malaria endemic area in Southern Ghana were determined by indirect ELISA. Titres against four single PfAMA1 alleles were compared with those against three different allele mixtures presumed to have a wider repertoire of epitope specificities. Associations of antibody levels with the incidence of clinical malaria as well as with previous exposure to parasites were also examined. RESULTS: Antibody titres against PfAMA1 alleles generally increased with age/exposure while antibody specificity for PfAMA1 variants decreased, implying that younger children (<= 5 years) elicit a more strain-specific antibody response compared to older children. Antibody titre measurements against the FVO and 3D7 AMA1 alleles gave the best titre estimates as these varied least in pair-wise comparisons with titres against all PfAMA1 allele mixtures. There was no association between antibody levels against any capture antigen and either clinical malaria incidence or parasite density. CONCLUSIONS: The current data shows that levels of naturally acquired antigen-specific antibodies, especially in infants and young children, are dependent on the antigenic allele used for measurement. This may be relevant to the interpretation of antibody titre data from measurements against single PfAMA1 alleles, especially in studies involving infants and young children who have experienced fewer infections. PMID- 22299618 TI - Dementia after age 75: survival in different severity stages and years of life lost. AB - Dementia is a known predictor of mortality, but little is known about disease duration. We therefore aimed to investigate the impact of dementia on survival by estimating years lived with the disease, in total and in different severity stages, and by comparing dementia to other major chronic disorders such as cancer and cardiovascular disease (CVD). During a 7.4-year follow-up of the Kungsholmen project, 371 incident dementia cases of the 1,307 dementia-free persons, aged 75+ at baseline, were clinically diagnosed (DSM-III-R criteria). Diagnoses of cancer and CVD were obtained from the national Stockholm Inpatient Registry System, active since 1969. Disease duration, hazard ratio (HR), and potential years of life lost (PYLL) were derived from Kaplan-Meier survival estimation, the Cox model, and standard life-table analysis, respectively. Dementia was a significant predictor of mortality (HR=1.7; 95% CI: 1.47-1.92) after adjustment for several covariates including comorbidity, accounting for 16% of all deaths. The mean (?SD) survival time after dementia diagnosis was 4.1 (?2.6) years, and more than 2 years were spent in moderate (14-month) and severe (12-month) stages. Women with dementia lived longer than men, as they survived longer in the severe stage (2.1 vs. 0.5 years among 75-84-year-old women compared to coetaneous men). The PYLL were 3.4 for dementia, 3.6 for CVD, and 4.4 for cancer. We found a similar impact of dementia and CVD on survival, but following diagnosis, persons with dementia, and especially women, spent half of their remaining lives in the severe disabling stages of the disease. PMID- 22299619 TI - The role of ER stress-induced apoptosis in neurodegeneration. AB - Post-mortem analyses of human brain tissue samples from patients suffering from neurodegenerative disorders have demonstrated dysfunction of the endoplasmic reticulum (ER). A common characteristic of the aforementioned disorders is the intracellular accumulation and aggregation of proteins due to genetic mutations or exogenous factors, leading to the activation of a stress mechanism known as the unfolded protein response (UPR). This mechanism aims to restore cellular homeostasis, however, if prolonged, can trigger pro-apoptotic signals, which are thought to contribute to neuronal cell death. The authors present evidence to support the role of ER stress-induced apoptosis in Alzheimer's, Parkinson's and Huntington's diseases, and further examine the interplay between ER dyshomeostasis and mitochondrial dysfunction, and the function of reactive oxygen species (ROS) and calcium ions (Ca(2+)) in the intricate relationship between the two organelles. Possible treatments for neurodegenerative diseases that are based on combating ER stress are finally presented. PMID- 22299621 TI - Insulin resistance in pediatric disease. PMID- 22299620 TI - Computer based classification of MR scans in first time applicant Alzheimer patients. AB - In this study, we aimed to classify MR images for recognizing Alzheimer Disease (AD) in a group of patients who were recently diagnosed by clinical history and neuropsychiatric exams by using non-biased machine-learning techniques. T1 weighted MRI scans of 31 patients with probable AD and 31 age- and gender-matched cognitively normal elderly were analyzed with voxel-based morphometry and classified by support vector machine (SVM), a machine learning technique. SVM could differentiate patients from controls with accuracy of 74% (sensitivity: 70% and specificity: 77%) when the whole brain was included the analyses. The classification accuracy was increased to 79% (sensitivity: 65 % and specificity: 93%) when the analyses restricted to hippocampus. Our results showed that SVM is a promising tool for diagnosis of AD, but needed to be improved. PMID- 22299622 TI - Dyslipidemias in children. PMID- 22299623 TI - Diabetes types 1 and 2 in the pediatric population. PMID- 22299624 TI - Substrate-free self-assembly approach toward large-area nanomembranes. AB - Free-standing two-dimensional nanostrucutures, such as graphene and semiconductor nanomembranes (NMs) featuring their integration with flexible polymer substrates, address applications in which electronic devices need to be stretchable or conformally positioned to nonplanar surfaces. We report a surfactant-directed surface assembly approach to producing large-area NMs at the water-air interface. The NMs were produced by employing the surfactants as templates as well as incorporating them in the crystal structures. By using excess amount of sodium dodecylsulfate (SDS), a tightly packed monolayer of dodecylsulfate (DS) ion was formed and directed the crystallization of submillimeter-sized zinc hydroxy dodecylsulfate (ZHDS) single-crystalline NMs over the entire water surface. This free-standing NM can be readily transferred to an arbitrary substrate and converted to ZnO via heat treatment. A flexible thin-film transistor was also fabricated using the transferred NMs and demonstrated reasonably good n-type transport properties. This approach circumvented the needs of single-crystalline substrates for making large-area NMs from materials that do not possess a laminate structure. It is a low-cost and large-scale synthesis technique and has great potential in developing NMs and flexible devices from various functional materials that are not feasible by conventional selective etching or delamination approaches. PMID- 22299625 TI - AsteriX: a Web server to automatically extract ligand coordinates from figures in PDF articles. AB - Coordinates describing the chemical structures of small molecules that are potential ligands for pharmaceutical targets are used at many stages of the drug design process. The coordinates of the vast majority of ligands can be obtained from either publicly accessible or commercial databases. However, interesting ligands sometimes are only available from the scientific literature, in which case their coordinates need to be reconstructed manually--a process that consists of a series of time-consuming steps. We present a Web server that helps reconstruct the three-dimensional (3D) coordinates of ligands for which a two dimensional (2D) picture is available in a PDF file. The software, called AsteriX, analyses every picture contained in the PDF file and attempts to determine automatically whether or not it contains ligands. Areas in pictures that may contain molecular structures are processed to extract connectivity and atom type information that allow coordinates to be subsequently reconstructed. The AsteriX Web server was tested on a series of articles containing a large diversity in graphical representations. In total, 88% of 3249 ligand structures present in the test set were identified as chemical diagrams. Of these, about half were interpreted correctly as 3D structures, and a further one-third required only minor manual corrections. It is principally impossible to always correctly reconstruct 3D coordinates from pictures because there are many different protocols for drawing a 2D image of a ligand, but more importantly a wide variety of semantic annotations are possible. The AsteriX Web server therefore includes facilities that allow the users to augment partial or partially correct 3D reconstructions. All 3D reconstructions are submitted, checked, and corrected by the users domain at the server and are freely available for everybody. The coordinates of the reconstructed ligands are made available in a series of formats commonly used in drug design research. The AsteriX Web server is freely available at http://swift.cmbi.ru.nl/bitmapb/. PMID- 22299626 TI - Antiviral treatment of cytomegalovirus infection: an update. AB - This editorial summarizes recent developments in the management of ganciclovir resistant human cytomegalovirus (HCMV) infections. All current drugs available for systemic treatment, including ganciclovir (GCV), valganciclovir, foscarnet and cidofovir, target the viral polymerase. However, all such compounds are hampered by dose-related toxicities and the emergence of resistance. Different approaches (e.g., PCR-based direct sequencing, pyrosequencing, mass spectrometry based comparative sequencing) allow the fast detection of resistant HCMV and are well suited to therapy monitoring. However, more studies are required on the dynamic of mixed HCMV populations under drug pressure. Alternate antiviral compounds with new mechanisms of action, such as artesunate, leflunomid, letermovir and maribavir, are now being investigated in clinical studies. An advantage of some of the new substances is lesser toxicity issues, which might lead to new prophylactic and treatment strategies. PMID- 22299627 TI - Yaoshanenolides A and B: new spirolactones from the bark of Machilus yaoshansis. AB - Two novel tricyclic spirolactones bearing long linear alkyl chains, yaoshanenolides A (1) and B (2), formed by Diels-Alder[4 + 2] cycloaddition of a molecule of each butenolide with beta-phellandrene, were isolated from the bark of Machilus yaoshansis. Their structures and absolute configurations were determined by extensive spectroscopic methods, especially 2D NMR and ECD data analysis. The proposed biosynthetic pathway is discussed. Both compounds exhibited nonselective cytotoxic activities against several human cancer cell lines. PMID- 22299628 TI - The mechanism of substrate inhibition in human indoleamine 2,3-dioxygenase. AB - Indoleamine 2,3-dioxygenase catalyzes the O(2)-dependent oxidation of L tryptophan (L-Trp) to N-formylkynurenine (NFK) as part of the kynurenine pathway. Inhibition of enzyme activity at high L-Trp concentrations was first noted more than 30 years ago, but the mechanism of inhibition has not been established. Using a combination of kinetic and reduction potential measurements, we present evidence showing that inhibition of enzyme activity in human indoleamine 2,3 dioxygenase (hIDO) and a number of site-directed variants during turnover with L tryptophan (L-Trp) can be accounted for by the sequential, ordered binding of O(2) and L-Trp. Analysis of the data shows that at low concentrations of L-Trp, O(2) binds first followed by the binding of L-Trp; at higher concentrations of L Trp, the order of binding is reversed. In addition, we show that the heme reduction potential (E(m)(0)) has a regulatory role in controlling the overall rate of catalysis (and hence the extent of inhibition) because there is a quantifiable correlation between E(m)(0) (that increases in the presence of L Trp) and the rate constant for O(2) binding. This means that the initial formation of ferric superoxide (Fe(3+)-O(2)(*-)) from Fe(2+)-O(2) becomes thermodynamically less favorable as substrate binds, and we propose that it is the slowing down of this oxidation step at higher concentrations of substrate that is the origin of the inhibition. In contrast, we show that regeneration of the ferrous enzyme (and formation of NFK) in the final step of the mechanism, which formally requires reduction of the heme, is facilitated by the higher reduction potential in the substrate-bound enzyme and the two constants (k(cat) and E(m)(0)) are shown also to be correlated. Thus, the overall catalytic activity is balanced between the equal and opposite dependencies of the initial and final steps of the mechanism on the heme reduction potential. This tuning of the reduction potential provides a simple mechanism for regulation of the reactivity, which may be used more widely across this family of enzymes. PMID- 22299629 TI - Application of acid-catalyzed hydrolysis of dispersed organic solvent in developing new microencapsulation process technology. AB - The aim of this study was to evaluate a new microencapsulation technology employing an acid-catalyzed solvent extraction method in conjunction to an emulsion-based microencapsulation process. Its process consisted of emulsifying a dispersed phase of poly(D,L-lactide-co-glycolide) and isopropyl formate in an aqueous phase. This step was followed by adding hydrochloric acid to the resulting oil-in-water emulsion, in order to initiate the hydrolysis of isopropyl formate dissolved in the aqueous phase. Its hydrolysis caused the liberation of water-soluble species, that is, isopropanol and formic acid. This event triggered continual solvent leaching out of emulsion droplets, thereby initiating microsphere solidification. This new processing worked well for encapsulation of progesterone and ketoprofen that were chosen as a nonionizable model drug and a weakly acidic one, respectively. Furthermore, the structural integrity of poly(D,L-lactide-co-glycolide) was retained during microencapsulation. The new microencapsulation technology, being conceptually different from previous approaches, might be useful in preparing various polymeric particles. PMID- 22299630 TI - Assembly of protein building blocks using a short synthetic peptide. AB - Combining proteins or their defined domains offers new enhanced functions. Conventionally, two proteins are either fused into a single polypeptide chain by recombinant means or chemically cross-linked. However, these strategies can have drawbacks such as poor expression (recombinant fusions) or aggregation and inactivation (chemical cross-linking), especially in the case of large multifunctional proteins. We developed a new linking method which allows site oriented, noncovalent, yet irreversible stapling of modified proteins at neutral pH and ambient temperature. This method is based on two distinct polypeptide linkers which self-assemble in the presence of a specific peptide staple allowing on-demand and irreversible combination of protein domains. Here we show that linkers can either be expressed or be chemically conjugated to proteins of interest, depending on the source of the proteins. We also show that the peptide staple can be shortened to 24 amino acids still permitting an irreversible combination of functional proteins. The versatility of this modular technique is demonstrated by stapling a variety of proteins either in solution or to surfaces. PMID- 22299631 TI - Nanoscale plasma chemistry enables fast, size-selective nanotube nucleation. AB - The possibility of fast, narrow-size/chirality nucleation of thin single-walled carbon nanotubes (SWCNTs) at low, device-tolerant process temperatures in a plasma-enhanced chemical vapor deposition (CVD) is demonstrated using multiphase, multiscale numerical experiments. These effects are due to the unique nanoscale reactive plasma chemistry (NRPC) on the surfaces and within Au catalyst nanoparticles. The computed three-dimensional process parameter maps link the nanotube incubation times and the relative differences between the incubation times of SWCNTs of different sizes/chiralities to the main plasma- and precursor gas-specific parameters and explain recent experimental observations. It is shown that the unique NRPC leads not only to much faster nucleation of thin nanotubes at much lower process temperatures, but also to better selectivity between the incubation times of SWCNTs with different sizes and chiralities, compared to thermal CVD. These results are used to propose a time-programmed kinetic approach based on fast-responding plasmas which control the size-selective, narrow chirality nucleation and growth of thin SWCNTs. This approach is generic and can be used for other nanostructure and materials systems. PMID- 22299632 TI - Identification and characterization of lipopolysaccharide binding protein (LBP) as an estrogen receptor alpha specific serum biomarker. AB - Estrogen Receptor alpha (ERalpha) and Estrogen Receptor beta (ERbeta) are steroid nuclear receptors that transduce estrogen signaling to control diverse physiological processes linked to reproduction, bone remodeling, behavior, immune response and endocrine-related diseases. In order to differentiate between ERalpha and ERbeta mediated effects in vivo, ER subtype selective biomarkers are essential. We utilized ERalpha knockout (AERKO) and ERbeta knockout (BERKO) mouse liver RNA and genome wide profiling to identify novel ERalpha selective serum biomarker candidates. Results from the gene array experiments were validated using real-time RT-PCR and subsequent ELISA's to demonstrate changes in serum proteins. Here we present data that Lipopolysacharide Binding Protein (LBP) is a novel liver-derived ERalpha selective biomarker that can be measured in serum. PMID- 22299633 TI - Extracellular nucleotide inhibits cell proliferation and negatively regulates Toll-like receptor 4 signalling in human progenitor endothelial cells. AB - Extracellular nucleotides mediate a wide range of physiological effects by interacting with plasma membrane P2 purinergic receptors. P2 receptors are expressed in certain kinds of stem cells, and function to induce cytokine expression and to modulate cell proliferation. We have analysed the expression and the function of P2 receptors in human umbilical cord blood-derived EPCs (endothelial progenitor cells). EPCs expressed P2X4,6,7 and P2Y2,4,11,13,14 receptors and extracellular ATP inhibited EPCs proliferation. As in a previous study, EPCs expressed functional TLR4 (Toll-like receptor 4) and activation of TLR4 by LPS (lipopolysaccharide) evoked a pro-inflammatory immune response. When human EPCs were stimulated with LPS and nucleotides, ATP or UTP inhibited the expression of pro-inflammatory cytokines including MCP-1 (monocyte chemoattractant protein-1), IFNalpha (interferon alpha), TNFalpha (tumour necrosis factor alpha) and adhesion molecule VCAM-1 (vascular cell adhesion molecule 1) induced by LPS. ATP and UTP also down-regulated the gene expression of TLR4, CD14 and MyD88 (myeloid differentiation factor 88), a TLR adaptor molecule, and protein expression of CD14 and MyD88. Moreover, the phosphorylation of NF-kappaB (nuclear factor kappaB) p65 induced by TLR4 activation was inhibited partly by ATP or UTP at concentrations of 1-5 MUM. These results suggest that extracellular nucleotides negatively regulate EPCs proliferation and TLR4 signalling. PMID- 22299634 TI - Risk of gastrointestinal illness associated with the consumption of rainwater: a systematic review. AB - The collection of rainwater for human consumption is a practice well established in many parts of the world. Much of the research to date regarding this inexpensive and sustainable source has focused on its microbiological or chemical quality and there have been no reviews of epidemiological evidence regarding actual health risks associated with rainwater consumption. Electronic bibliographic databases were searched for epidemiological studies that attempted to quantify the risk of gastrointestinal disease linked to the consumption of harvested rainwater. Online databases were searched from the oldest date up to January 2011. Both observational and experimental studies were included. In addition, reference sections of key articles were searched and authors of previous studies were contacted where appropriate. Studies were assessed for relevance independently and in duplicate. Searches returned a total of 764 articles, 13 met inclusion criteria, 5 of these were outbreak reports, and 9 were studies of other design types. Pooled subgroup analysis suggests that rainwater is associated with reduced risk of illness compared to unimproved supplies (relative risk 0.57 95% CI 0.42, 0.77). There was no significant difference in risk in the pooled analysis of studies that compared rainwater to improved water supplies (relative risk 0.82 95% CI 0.38, 1.73). However, there was heterogeneity with one study showing an excess risk of campylobacteriosis. Classification of outbreak reports determined that 4 reports were "strongly associated with rainwater" while 1 report was "probably associated with rainwater". We conclude that the evidence suggests that rainwater is safer than water from unimproved water supplies. Where feasible rainwater harvesting should be encouraged as a step toward achieving millennium development targets. PMID- 22299635 TI - Morphology transformation of hybrid micelles self-assembled from rod-coil block copolymer and nanoparticles. AB - Hybrid polymeric micelles self-assembled from a mixture containing poly(gamma benzyl-L-glutamate)-block-poly(ethylene glycol) (PBLG-b-PEG) block copolymer and gold nanoparticles (AuNPs) were prepared. The effect of AuNPs on the self assembly behavior of PBLG-b-PEG was studied both experimentally by transmission electron microscopy, scanning electron microscopy, and laser light scattering and computationally using dissipative particle dynamics (DPD) simulations. It was found that, the pure PBLG-b-PEG block copolymer self-assembles into long cylindrical micelles. By introducing AuNPs to the stock block copolymer solution, the formed aggregate morphology transforms to spherical micelles. The DPD simulation results well reproduced the morphological transformations observed in the experiments. And the simulation revealed that the main reason for the aggregate morphology transformation is the breakage of ordered packing of PBLG rods in micelle core by the added nanoparticles. Moreover, from the DPD simulations, the distribution information on nanoparticles was obtained. The nanoparticles were found to prefer to locate near the core/shell interface as well as in the core center of the micelles. The combination of experimental and simulation methods lead to a comprehensive understanding of such a complex self assembly system. PMID- 22299636 TI - Physical therapy management of entrapment of the superficial peroneal nerve in the lower leg: a case report. AB - This case report describes a 40-year-old male who presented with complaints of pain in the left lower lateral one-third of the leg. Tenderness was elicited 9.7 cm above the lateral malleoli with a positive Tinel's sign at the same site causing radiating pain into the foot (visual analog scale (VAS) score of 6.3 cm). Physical diagnosis for entrapment of the superficial peroneal nerve at the site of the peroneal tunnel was entertained based on clinical examination and three positive provocation tests. Conventionally, treatment for this type of entrapment has been surgical decompression by splitting the crural fascia, with successful outcomes. This is potentially a first-time report describing physical therapy management of entrapment mechanical interface with pain modalities, soft tissue mobilization, and neural mobilization. Reduction of pain was noted in this patient (VAS score of 0 cm by the sixth session) with complete pain resolution maintained at a six-month follow-up. PMID- 22299637 TI - Friction in carborane-based molecular rotors driven by gas flow or electric field: classical molecular dynamics. AB - Friction in molecular rotors is examined by classical molecular dynamics simulations for grid-mounted azimuthal dipolar molecular rotors, whose rotation is either allowed to decay freely or is driven at GHz frequencies by a flow of rare gas or by a rotating electric field. The rotating parts (rotators) are propeller-shaped. Their two to six blades consist of condensed aromatic rings and are attached to a deltahedral carborane hub, whose antipodal carbons carry [n]staffane axles mounted on a square molecular grid. The dynamic friction constant eta has been derived in several independent ways with similar results. Analysis of free rotation decay yields eta as a continuous exponentially decreasing function of rotor frequency. The calculated dependence of friction torque on frequency resembles the classical macroscopic Stribeck curve. Its relation to rotational potential energy barriers and the key role of the rate of intramolecular vibrational redistribution (IVR) of energy and angular momentum from rotator rotation to other modes are considered in two limiting regimes. (i) In the strongly overdamped regime, rotation is much slower than IVR, and effective friction can be expressed through potential barriers to rotation. (ii) In the strongly underdamped regime, rotation is much faster than IVR, whose rate then determines friction. PMID- 22299640 TI - Novel ABCA-12 mutations leading to recessive congenital ichthyosis. AB - Mutations in the keratinocyte lipid transporter adenosine triphosphate-binding cassette A12 (ABCA12) are known to cause harlequin ichthyosis. More recently, mutations in this gene have been demonstrated to cause other phenotypes within the spectrum of recessive congenital ichthyosis. We report the case of an infant with novel heterozygous mutations in ABCA12 who exhibited features and a clinical course more consistent with congenital ichthyosiform erythroderma than harlequin ichthyosis. PMID- 22299641 TI - Comparison of sampling methods for the assessment of indoor microbial exposure. AB - Indoor microbial exposure has been related to allergy and respiratory disorders. However, the lack of standardized sampling methodology is problematic when investigating dose-response relationships between exposure and health effects. In this study, different sampling methods were compared regarding their assessment of microbial exposures, including culturable fungi and bacteria, endotoxin, as well as the total inflammatory potential (TIP) of dust samples from Danish homes. The Gesamtstaubprobenahme (GSP) filter sampler and BioSampler were used for sampling of airborne dust, whereas the dust fall collector (DFC), the electrostatic dust fall collector (EDC), and vacuum cleaner were used for sampling of settled dust. The GSP assessed significantly higher microbial levels than the BioSampler, yet measurements from both samplers correlated significantly. Considerably higher levels of fungi, endotoxin, and TIP were found in the EDC compared with the DFC, and regarding fungi, the EDC correlated more strongly and significantly with vacuumed dust than the DFC. Fungi in EDC and vacuum dust correlated most strongly with airborne dust, and in particular, the measurements from the EDC associated well with those from GSP. Settled dust from the EDC was most representative of airborne dust and may thus be considered as a surrogate for the assessment of indoor airborne microbial exposure. PRACTICAL IMPLICATIONS: Significant discrepancies between sampling methods regarding indoor microbial exposures have been revealed. This study thus facilitates comparison between methods and may therefore be used as a frame of reference when studying the literature or when conducting further studies on indoor microbial exposure. Results also imply that the relatively simple EDC method for the collection of settled dust may be used as an alternative to otherwise tedious and time consuming airborne dust sampling. PMID- 22299642 TI - Assessment of computer task performance (ACTP) of children and youth with intellectual and developmental disability. AB - The aims of this study were to assess the reliability and validity of the Arabic translation of the Assessment of Computer Task Performance (ACTP) when used for children with Intellectual and Developmental Disabilities (IDD) and to determine the relationship between participants' performance when using an adapted pointing device and the teacher's satisfaction of their performance. Thirty boys and girls, Arabic speakers, 6- 21 years old, who had moderate IDD, participated in the study. Two expert occupational therapists used the ACTP to evaluate the performance of five standardized timed computer tasks. The Quebec User Evaluation of Satisfaction with Assistive Technology was used to evaluate the teachers' satisfaction with the prescribed pointing device. The sample in the current study performed slower than typically developing children and youth, and slower than participants with motor impairments, examined in previous studies. Differences were found in performance time between girls and boys, and between three diagnostic subgroups. The participants' success scores of computer performance correlated significantly with the teacher's satisfaction with the prescribed pointing device. Demonstration of the validity and reliability of the Arabic version of the ACTP-Child enables wider use of this tool which is now available in four languages and diverse cultural settings and disability populations, including children and youth with significant IDD. PMID- 22299643 TI - Contact dermatitis to para-phenylenediamine in hair dye following sensitization to black henna tattoos - an ongoing problem. AB - BACKGROUND: The increased frequency of case reports of allergic contact dermatitis from non-permanent black henna tattoos in recent years shows the popularity of this form of body painting. PATIENTS AND METHODS: Seven patients presented with allergic contact dermatitis after initial hair or eyelash dyeing. They all had a history of a previous reaction from a black henna tattoo. All were patch tested with the European standard patch test series and the standard supplemental series, as well as special series for dyes and hairdressers. RESULTS: All seven patients showed a positive reaction in patch testing with para phenylenediamine (PPD) (0.3 % and/or 1.0 % in pet.). Five patients also had positive reactions to other dyes such as aminophenol, para-toluene diamine, disperse orange and yellow and four patients reacted to benzocaine. These were interpreted as cross-reactions. The time from sensitization by the black henna tattoo to the onset of allergic contact dermatitis after hair dyeing was an average of 6.2 years. CONCLUSIONS: The most common cause of allergic contact dermatitis after black henna tattoos is PPD. Both the long skin contact and the high concentrations of PPD increase the risk of sensitization. Allergic contact dermatitis may be followed by post-inflammatory hyper- or hypopigmentation, scarring and lifelong sensitization, which can have occupational impact, especially for hair dressers and cosmeticians. PMID- 22299644 TI - Urinary pharmacokinetic methodology to determine the relative lung bioavailability of inhaled beclometasone dipropionate. AB - AIM: Urinary pharmacokinetic methods have been identified to determine the relative lung and systemic bioavailability after an inhalation. We have extended this methodology to inhaled beclometasone dipropionate (BDP). METHOD: Ethics Committee approval was obtained and all subjects gave consent. Twelve healthy volunteers received randomized doses, separated by >7 days, of 2000 ug BDP solution with (OralC) and without (Oral) 5 g oral charcoal, 10,100 ug inhalations from a Qvar((r)) Easibreathe metered dose inhaler (pMDI) with (QvarC) and without (Qvar) oral charcoal and eight 250 ug inhalations from a Clenil((r)) pMDI (Clenil). Subjects provided urine samples at 0, 0.5, 1, 2, 3, 5, 8, 12 and 24 h post study dose. Urinary concentrations of BDP and its metabolites, beclometasone 17-monopropionate (17-BMP) and beclometasone (BOH) were measured. RESULTS: No BDP, 17-BMP or BOH were detected in any samples post OralC dosing. Post oral dosing no BDP was detected in all urine samples and no 17-BMP or BOH was excreted in the first 30 min. Significantly more (P < 0.001) BDP, 17-BMP and BOH were excreted in the first 30 min and the cumulative 24 h urinary excretions post Qvar and Clenil compared with Oral. The mean ratio (90% confidence interval) of the 30 min urinary excretions for Qvar compared with Clenil was 231.4 (209.6, 255.7) %. CONCLUSION: The urinary pharmacokinetic methodology to determine the relative lung and systemic bioavailability post inhalation, using 30 min and cumulative 24 h post inhalation samples, applies to BDP. The ratio between Qvar and Clenil is consistent with related clinical and lung deposition studies. PMID- 22299645 TI - Neonates presenting with temperature symptoms: role in the diagnosis of early onset sepsis. AB - BACKGROUND: In this study, we aimed to evaluate the role of fever, hypothermia, and temperature instability in term and preterm newborns during the first 3 days of life and to identify risk factors for early onset sepsis (EOS) among newborns presenting with these temperature symptoms. METHODS: In this retrospective cohort study set in our level III neonatal intensive care unit, we included all newborns hospitalized within the first 24 h of life from 2004 to 2007. RESULTS: Of 851 newborns, 127 presented with temperature symptoms during the first 3 days of life (15%): 69 had fever, 69 had hypothermia, and 55 had temperature instability (8%, 8%, and 6%, respectively). Of 127 newborns presenting with temperature symptoms, 14 had culture-proven EOS/pneumonia (33% of all 42 newborns with culture-proven EOS/pneumonia), 67 had clinical EOS (30% of all 209 newborns with clinical EOS) and 46 were EOS-negative (8% of all 600 EOS-negatives). Factors associated with culture-proven EOS/pneumonia in newborns presenting with temperature symptoms were maternal fever (P = 0.009), chorioamnionitis (P < 0.001), antibiotic therapy of the mother (P = 0.04), poor skin color (P = 0.001) and syndrome of persistent fetal circulation (P = 0.01). CONCLUSIONS: Every seventh newborn hospitalized at our neonatal intensive care unit developed fever, hypothermia and/or temperature instability during the first 3 days of life. Two-thirds of them had culture proven or clinical sepsis. Temperature symptoms were rarely observed in EOS negative newborns (8%) but despite low sensitivity, were highly specific for bacterial infection in preterm and term newborns. PMID- 22299646 TI - Proton-coupled electron-transfer reduction of dioxygen catalyzed by a saddle distorted cobalt phthalocyanine. AB - Proton-coupled electron-transfer reduction of dioxygen (O(2)) to afford hydrogen peroxide (H(2)O(2)) was investigated by using ferrocene derivatives as reductants and saddle-distorted (alpha-octaphenylphthalocyaninato)cobalt(II) (Co(II)(Ph(8)Pc)) as a catalyst under acidic conditions. The selective two electron reduction of O(2) by dimethylferrocene (Me(2)Fc) and decamethylferrocene (Me(10)Fc) occurs to yield H(2)O(2) and the corresponding ferrocenium ions (Me(2)Fc(+) and Me(10)Fc(+), respectively). Mechanisms of the catalytic reduction of O(2) are discussed on the basis of detailed kinetics studies on the overall catalytic reactions as well as on each redox reaction in the catalytic cycle. The active species to react with O(2) in the catalytic reaction is switched from Co(II)(Ph(8)Pc) to protonated Co(I)(Ph(8)PcH), depending on the reducing ability of ferrocene derivatives employed. The protonation of Co(II)(Ph(8)Pc) inhibits the direct reduction of O(2); however, the proton-coupled electron transfer from Me(10)Fc to Co(II)(Ph(8)Pc) and the protonated [Co(II)(Ph(8)PcH)](+) occurs to produce Co(I)(Ph(8)PcH) and [Co(I)(Ph(8)PcH(2))](+), respectively, which react immediately with O(2). The rate-determining step is a proton-coupled electron transfer reduction of O(2) by Co(II)(Ph(8)Pc) in the Co(II)(Ph(8)Pc)-catalyzed cycle with Me(2)Fc, whereas it is changed to the electron-transfer reduction of [Co(II)(Ph(8)PcH)](+) by Me(10)Fc in the Co(I)(Ph(8)PcH)-catalyzed cycle with Me(10)Fc. A single crystal of monoprotonated [Co(III)(Ph(8)Pc)](+), [Co(III)Cl(2)(Ph(8)PcH)], produced by the proton-coupled electron-transfer reduction of O(2) by Co(II)(Ph(8)Pc) with HCl, was obtained, and the crystal structure was determined in comparison with that of Co(II)(Ph(8)Pc). PMID- 22299647 TI - Methylation capacity in children with severe cerebral palsy. AB - BACKGROUND: Methylation cycle and folate-mediated one-carbon metabolism maintenance is important for many physiological processes including neurotransmitter regulation, nerve myelination and DNA synthesis. These processes play an indispensible role in growth and development, as well as in cognitive function and neuromuscular stability, which are key issues in children with severe cerebral palsy (CP). METHODS: Blood samples were collected from children with severe CP (n = 24) and age-matched typically developing healthy controls (n = 24), as an exploratory study. The CP group was divided into orally (O) or enterally fed via percutaneous endoscopic gastrostomy (E). Concentrations of red cell folate (RCF), methylmalonic acid (MMA), mean cell volume (MCV), homocysteine (Hcy), cystathionine, choline, betaine and urate were assayed. RESULTS: Homocysteine was increased in both O mean (+/-SD) = 6.28 (+/-1.81 MUM) and E = 6.03 (+/-1.28), vs. controls = 5.07 (+/-0.98) P = 0.02. Higher MMA was found in controls = 157 (+/-54) and O = 141 (+/-101), vs. E = 88(+/-21) P = 0.05. RCF was higher in E = 1422 (+/-70 nM) vs. O = 843 (+/-80) and controls = 820 (+/-43) P < 0.001. MCV z-scores were elevated in E = 3.1 (+/-1.8) and O = 1.1 (+/-1.1) compared with controls = -0.2 (+/-1.1) P < 0.001. Urate was significantly reduced in O = -0.64 (+/-1.38) and E = -0.87 (+/-0.71), vs. controls = 0.18 (+/-0.62) P = 0.006. CONCLUSIONS: Raised MCV in the presence of elevated red cell folate, adequate B12 status and low plasma urate suggest potential methyltetrahydrofolate trapping and impaired purine synthesis. Well-documented malnutrition issues in O may explain differences between CP groups. These data support the hypothesis of possible dysregulation in methylation capacity and/or folate one-carbon metabolism, although more research is needed to elucidate a precise mechanism. PMID- 22299648 TI - Linear skin atrophy preceding calcinosis cutis in pseudo pseudohypoparathyroidism. AB - Albright hereditary osteodystrophy (AHO) is a syndrome caused by inactivating mutations in the GNAS (guanine nucleotide-binding protein, alpha-stimulating) gene. Patients with AHO have short stature, obesity, brachydactyly and subcutaneous calcifications. AHO can be associated with pseudohypoparathyroidism type IA (PHP-IA) with upregulation of parathyroid hormone, whereas in pseudo pseudohypoparathyroidism (PPHP), an endocrinopathy is not present. We report the case of a 5-month-old male infant who presented with slowly progressive linear atrophic skin lesions. The histological findings showed evidence of dermal hypoplasia. The child's father had PHP-IA. Four months after presentation, the infant developed calcifications within the pre-existent atrophic lesions. No alterations in calcium metabolism were noted. Analysis of the GNAS gene identified a short duplication leading to a frameshift mutation. We conclude that linear atrophic skin lesions may be an early sign of imminent cutaneous calcifications in AHO. PMID- 22299649 TI - Organ donation and Moyamoya disease. PMID- 22299650 TI - Asian age-related macular degeneration phenotyping study: rationale, design and protocol of a prospective cohort study. AB - BACKGROUND: Current knowledge of the phenotypic characteristics (e.g. clinical features, risk factors, natural history and treatment response) of age-related macular degeneration (AMD) in Asians remains limited. This report summarizes the rationale and study design of a prospective observational study of Asian neovascular AMD, including polypoidal choroidovasculopathy variant. DESIGN: The Asian AMD phenotyping study is a prospective, observational clinical study of Asian patients with neovascular AMD or polypoidal choroidovasculopathy in three tertiary eye centres in Singapore. PARTICIPANTS: The study aims to recruit 500 consecutive patients from the retinal clinics of three tertiary eye centres in Singapore. METHODS: Standardized examination procedures include interviews, a comprehensive eye examination, digital photography of the retina, fundus fluorescein and indocyanine green angiography and spectral domain optical coherence tomography using a standardized protocol. Blood samples were collected for biochemical analyses and stored for genetic and proteomic studies. MAIN OUTCOME MEASURES: The aim of the study was to build a comprehensive database of clinical, angiographic, functional and natural history data of Asian AMD over a 12-month follow-up period. RESULTS: This article discusses the methodology and design of this prospective multi-centred study. CONCLUSION: This study will provide in-depth longitudinal data of the evolution of clinical features, risk factors, natural history and treatment pattern and response of Asian AMD and polypoidal choroidovasculopathy, allowing unique insights into pathogenesis and the design of new treatment strategies. PMID- 22299651 TI - Microbial production of propionic acid from propionibacteria: current state, challenges and perspectives. AB - Propionic acid (PA) is an important building block chemical and finds a variety of applications in organic synthesis, food, feeding stuffs, perfume, paint and pharmaceutical industries. Presently, PA is mainly produced by petrochemical route. With the continuous increase in oil prices, public concern about environmental pollution, and the consumers' desire for bio-based natural and green ingredients in foods and pharmaceuticals, PA production from propionibacteria has attracted considerable attention, and substantial progresses have been made on microbial PA production. However, production of PA by propionibacteria is facing challenges such as severe inhibition of end-products during cell growth and the formation of by-products (acetic acid and succinic acid). The integration of reverse metabolic engineering and systematic metabolic engineering provides an opportunity to significantly improve the acid tolerance of propionibacteria and reduce the formation of by-products, and makes it feasible to strengthen the commercial competition of biotechnological PA production from propionibacteria to be comparable to the petrochemical route. PMID- 22299652 TI - Proline 107 is a major determinant in maintaining the structure of the distal pocket and reactivity of the high-spin heme of MauG. AB - The diheme enzyme MauG catalyzes a six-electron oxidation required for posttranslational modification of a precursor of methylamine dehydrogenase (preMADH) to complete the biosynthesis of its protein-derived tryptophan tryptophylquinone (TTQ) cofactor. Crystallographic studies had shown that Pro107, which resides in the distal pocket of the high-spin heme of MauG, changes conformation upon binding of CO or NO to the heme iron. In this study, Pro107 was converted to Cys, Val, and Ser by site-directed mutagenesis. The structures of each of these MauG mutant proteins in complex with preMADH were determined, as were their physical and catalytic properties. P107C MauG was inactive, and the crystal structure revealed that Cys107 had been oxidatively modified to a sulfinic acid. Mass spectrometry revealed that this modification was present prior to crystallization. P107V MauG exhibited spectroscopic and catalytic properties that were similar to those of wild-type MauG, but P107V MauG was more susceptible to oxidative damage. The P107S mutation caused a structural change that resulted in the five-coordinate high-spin heme being converted to a six coordinate heme with a distal axial ligand provided by Glu113. EPR and resonance Raman spectroscopy revealed this heme remained high-spin but with greatly increased rhombicity as compared to that of the axial signal of wild-type MauG. P107S MauG was resistant to reduction by dithionite and reaction with H(2)O(2) and unable to catalyze TTQ biosynthesis. These results show that the presence of Pro107 is critical in maintaining the proper structure of the distal heme pocket of the high-spin heme of MauG, allowing exogenous ligands to bind and directing the reactivity of the heme-activated oxygen during catalysis, thus minimizing the oxidation of other residues of MauG. PMID- 22299653 TI - Morphological preservation of carbonaceous plant fossils in blueschist metamorphic rocks from New Zealand. AB - Morphological and chemical evidence of ancient life is widespread in sedimentary rocks retrieved from shallow depths in the Earth's crust. Metamorphism is highly detrimental to the preservation of biological information in rocks, thus limiting the geological record in which traces of life might be found. Deformation and increasing pressure/temperature during deep burial may alter the morphology as well as the composition and structure of both the organic and mineral constituents of fossils. However, microspore fossils have been previously observed in intensely metamorphosed rocks. It has been suggested that their small size, and/or the nature of the polymer composing their wall, and/or the mineralogy of their surrounding matrix were key parameters explaining their exceptional preservation. Here, we describe the remarkable morphological preservation of plant macrofossils in blueschist metamorphic rocks from New Zealand containing lawsonite. Leaves and stems can be easily identified at the macroscale. At the microscale, polygonal structures with walls mineralized by micas within the leaf midribs and blades may derive from the original cellular ultrastructure or, alternatively, from the shrinkage during burial of the gelified remnants of the leaves in an abiotic process. Processes and important parameters involved in the remarkable preservation of these fossils during metamorphism are discussed. Despite the excellent morphological preservation, the initial biological polymers have been completely transformed to graphitic carbonaceous matter down to the nanometer scale. This occurrence demonstrates that plant macrofossils may experience major geodynamic processes such as metamorphism and exhumation involving deep changes and homogenization of their carbon chemistry and structure but still retain their morphology with remarkable integrity even if they are not shielded by any hard-mineralized concretion. PMID- 22299654 TI - Intravenous thrombolysis in ischemic stroke patients with isolated homonymous hemianopia. AB - BACKGROUND: Patients with posterior ischemic stroke were usually excluded from thrombolytic treatment in clinical trials and clinical practice, and little is known about effectiveness of thrombolysis treatment in such patients who may end up with severe disability. AIMS OF THE STUDY: We aimed to describe the outcome of acute ischemic stroke patients presenting with isolated homonymous hemianopia and treated with intravenous thrombolysis. METHODS: A case report of three patients presenting with homonymous hemianopia owing to posterior circulation stroke treated with intravenous thrombolysis at the Helsinki University Central Hospital. Main outcome measures were modified Rankin Scale and neuropsychological examination at 3 months after thrombolysis. We further evaluated Goldmann visual field examination at 6 months. RESULTS: No acute findings appeared on admission non-contrast head-computed tomography scan. All patients had a perfusion deficit on admission-computed tomography perfusion imaging. All patients scored 0 on 3 month modified Rankin Scale, and their neuropsychological evaluation was normal. Goldmann examination revealed no visual field deficit in both female patients, and a modest visual field defect was detected in the male patient. CONCLUSIONS: Our experience encourages application of intravenous thrombolytic treatment (especially when supported with multimodality neuroimaging) in patients with homonymous hemianopia, for which rehabilitation options are limited. PMID- 22299655 TI - Synthesis of Au@Ag core-shell nanocubes containing varying shaped cores and their localized surface plasmon resonances. AB - We have synthesized Au@Ag core-shell nanocubes containing Au cores with varying shapes and sizes through modified seed-mediated methods. Bromide ions are found to be crucial in the epitaxial growth of Ag atoms onto Au cores and in the formation of the shell's cubic shape. The Au@Ag core-shell nanocubes exhibit very abundant and distinct localized surface plasmon resonance (LSPR) properties, which are core-shape and size-dependent. With the help of theoretical calculation, the physical origin and the resonance mode profile of each LSPR peak are identified and studied. The core-shell nanocrystals with varying shaped cores offer a new rich category for LSPR control through the plasmonic coupling effect between core and shell materials. PMID- 22299657 TI - Somatic mitochondrial DNA mutations in cancer escape purifying selection and high pathogenicity mutations lead to the oncocytic phenotype: pathogenicity analysis of reported somatic mtDNA mutations in tumors. AB - BACKGROUND: The presence of somatic mitochondrial DNA (mtDNA) mutations in cancer cells has been interpreted in controversial ways, ranging from random neutral accumulation of mutations, to positive selection for high pathogenicity, or conversely to purifying selection against high pathogenicity variants as occurs at the population level. METHODS: Here we evaluated the predicted pathogenicity of somatic mtDNA mutations described in cancer and compare these to the distribution of variations observed in the global human population and all possible protein variations that could occur in human mtDNA. We focus on oncocytic tumors, which are clearly associated with mitochondrial dysfunction. The protein variant pathogenicity was predicted using two computational methods, MutPred and SNPs&GO. RESULTS: The pathogenicity score of the somatic mtDNA variants were significantly higher in oncocytic tumors compared to non-oncocytic tumors. Variations in subunits of Complex I of the electron transfer chain were significantly more common in tumors with the oncocytic phenotype, while variations in Complex V subunits were significantly more common in non-oncocytic tumors. CONCLUSIONS: Our results show that the somatic mtDNA mutations reported over all tumors are indistinguishable from a random selection from the set of all possible amino acid variations, and have therefore escaped the effects of purifying selection that act strongly at the population level. We show that the pathogenicity of somatic mtDNA mutations is a determining factor for the oncocytic phenotype. The opposite associations of the Complex I and Complex V variants with the oncocytic and non-oncocytic tumors implies that low mitochondrial membrane potential may play an important role in determining the oncocytic phenotype. PMID- 22299659 TI - A brief history of APP secretases, their substrates and their functions. PMID- 22299660 TI - PP2A and Alzheimer disease. AB - Phosphorylation and, therefore, binding capacity of microtubule-associated protein tau is regulated by specific kinases and phosphatases. Activation of tau kinases plays a crucial role in tau- hyper-phosphorylation in Alzheimer disease (AD) and related tauopathies. Among phosphatases, protein phosphatase 2A, PP2A, is a principal tau dephosphorylating enzyme in the brain. PP2A acts as trimer composed of a catalytic (PP2A C), a scaffolding (PP2A A) and a regulatory (PP2 AB; B55alpha) subunit. Several abnormalities of PP2A have been reported in AD, including decreased mRNA and protein levels of the PP2A C (not replicated by other studies); decreased protein levels of the PP2A A and B55alpha; reduced PP2A C methylation at Leu309 due to impaired function methyltransferase type IV; increased PP2A C phosphorylation at Tyr307; up-regulation of the PP2A inhibitors I1 and I2; and loss of enzymatic activity. These observations indicate that PP2A is a putative target of therapeutic intervention considering that enhancing PP2A activity would decrease tau hyper-phosphorylation in AD. In spite of these achievements further studies are needed to replicate the reported individual different alterations converging in PP2A in AD. PMID- 22299658 TI - Longer ongoing task delay intervals exacerbate prospective memory deficits in HIV associated neurocognitive disorders (HAND). AB - The delay interval between encoding a future intention and detection of the retrieval cue is an essential feature of prospective memory (PM). McDaniel and Einstein's ( 2000 ) multiprocess theory posits that greater demands are placed on strategic monitoring processes as the delay interval lengthens. This hypothesis was examined in HIV-associated neurocognitive disorders (HAND), which are associated with strategic dyscontrol of PM, likely secondary to prefrontostriatal circuit pathology. Seventy-eight seronegative adults and 49 individuals with HAND comprised the study groups, which were comparable with regard to demographic, psychiatric, and substance use factors. As part of a comprehensive neuropsychological evaluation, participants were administered a well-validated PM measure that included short (2-min) and long (15-min) task delay interval scales that utilized a standardized word search as the ongoing task. Results revealed a significant interaction of group and delay interval, with significant effects of HAND on PM at long, but not short, delay. The long-delay PM effect in HAND was driven primarily by deficits in time-based PM and was most strongly associated with markers of executive dysfunction. In concordance with the multiprocess theory, individuals with HAND were disproportionately vulnerable to PM deficits at longer ongoing task delay intervals, which appear to be driven by strategic dyscontrol of PM that is consistent with the preferential disruption of prefrontal systems in neuroAIDS (neurological complications of AIDS). Difficulty with successfully completing PM tasks following a longer delay could manifest in real-world problems, such as medication nonadherence and unemployment, and characterizing this specific deficit may inform remediation strategies. PMID- 22299661 TI - The effect of different dialysate magnesium concentrations on QTc dispersion in hemodialysis patients. AB - BACKGROUND: Electrolyte changes during dialysis affect corrected QT (QTc) and QTc dispersion (QTcd), a surrogate marker of arrhythmogenicity. The impact of magnesium on QTcd is not clear. METHODS: Twenty-two stable patients on maintenance hemodialysis were enrolled in this study. Each underwent two consecutive hemodialysis sessions at least 2 days apart, the first against normal magnesium dialysate (with magnesium at 1.8 mg/dL) followed by a low magnesium dialysate (with magnesium at 0.6 mg/dL). Pre- and post-dialysis weights, blood pressure, electrolytes, and 12-lead surface EKG were recorded. The QT interval and the QTcd were calculated before and after dialysis in both sessions. RESULTS: Of 22 patients, 16 were female. The mean age +/- SD was 53.7 +/- 18.0 years. The mean change of QTcd (pre- vs. post-dialysis) was 9.5 ms (p = 0.120) and 9.3 ms (p = 0.145) in low and normal magnesium groups, respectively. Using univariate analysis, there was a statistically significant decrease in the mean blood pressure, weight, potassium, magnesium, and QTc interval post-dialysis (compared to pre-dialysis) in both groups (p <= 0.049). Post-dialysis concentrations of sodium and calcium were unchanged (compared to pre-dialysis) but bicarbonate increased with both dialysate groups (p < 0.001). The mean change of QTcd was not significant pre- versus post-dialysis by univariate analysis in either group. Multiple linear regression analysis adjusting for pertinent factors did not change the results in either of the two groups. CONCLUSION: Using a low magnesium dialysate bath in hemodynamically stable hemodialysis patients without preexisting advanced cardiac disease does not significantly impact QTcd. PMID- 22299662 TI - Sporotrichosis on the face of a 7-year-old boy following a bicycle accident. AB - A 7-year-old boy presented with an annular verrucous plaque on the chin of 5 weeks duration. The lesion occurred after a bicycle accident and was unresponsive to antibiotics. Fungal culture grew Sporothrix schenckii. Sporotrichosis should be considered and fungal culture obtained whenever a nodule or plaque fails to respond to initial treatment. PMID- 22299663 TI - A psychophysiological comparison of on-sight lead and top rope ascents in advanced rock climbers. AB - Research suggests that lead climbing is both physiologically and psychologically more stressful than top rope climbing for intermediate performers. This observation may not be true for advanced climbers, who train regularly on lead routes and are accustomed to leader falls. The aim of this study was to compare the psychophysiological stresses of lead and top rope on-sight ascents in advanced rock climbers. Twenty-one climbers (18 men and three women) ascended routes near or at the best of their ability (22 Ewbank). Psychological stress was measured preclimb using the Revised Comparative State Anxiety Inventory (CSAI 2R). Plasma cortisol was sampled at six intervals. The volume of oxygen (VO2 ) and heart rate (Hr) were measured throughout the climbs. No significant differences were found in self-confidence, somatic, or cognitive anxiety between the conditions lead and top rope. No significant differences in plasma cortisol concentration were found between any time points. No significant relationships were found between cortisol and any CSAI-2R measures. No significant differences were found between conditions for VO2 or blood lactate concentration. During the lead climb, Hr was significantly elevated during the last part of the route. Findings suggest that advanced rock climbers do not find lead climbing to be more stressful than top rope climbing during an on-sight ascent. PMID- 22299665 TI - Evaluation of patients with vertigo of vertebrobasilar insufficiency origin using auditory brainstem response, electronystagmography, and transcranial Doppler. AB - OBJECTIVES: Vertigo can be a manifestation of underlying vertebrobasilar stroke in older adults. The study objectives were to investigate the correlation, sensitivity, and specificity of the auditory brainstem response (ABR), electronystagmorgraphy (ENG), and transcranial Doppler (TCD) collectively to distinguish between vertigo due to vertebrobasilar insufficiency (VBI) and vertigo due to non-VBI. DESIGN: Prospective experimental study comparing ENG, ABR, and TCD battery findings between two groups of patients with vertigo and a control group. STUDY SAMPLE: Participants included 14 patients with vertigo of VBI origin, 14 patients with vertigo of non-VBI, and 11 matched controls. RESULTS: Participants with VBI had more abnormal findings in the ENG (86%), TCD (72%), and ABR (64%) compared to the non-VBI group (64%, 21%, and 7%, respectively) and the control group. The combined battery revealed positive correlations, 64% sensitivity, and 84% positive predictive value (PPV) in the VBI group, and 100% specificity with lack of correlations in the non-VBI group. CONCLUSIONS: The modest sensitivity and PPV helps with early detection of VBI, thus preventing risk of vertebrobasilar stroke in 84% to 64% of patients. The 100% specificity in the non-VBI group rules out VBI, thus reducing the referral rate for unnecessary, diagnostic evaluations and ineffective treatment. PMID- 22299666 TI - DPOAEs and contralateral acoustic stimulation and their link to sound hypersensitivity in children with autism. AB - OBJECTIVE: The hypersensitivity of children with autism to sound is a relatively unexplained behavior. The goal of the current study was to investigate the DPOAE characteristics of children with autism compared to a control group. DESIGN: DPOAEs with and without contralateral stimuli were measured in two groups in three different conditions. STUDY SAMPLE: The study employed 14 children with autism and a control group with 28 age-matched participants. RESULTS: In the without-contralateral stimulus condition, the overall S/N of DPOAEs was greater for the control group compared to the autism group (p < 0.0005). For both groups, the DPOAE S/N increased as a function of frequency in both ears. In the with contralateral stimulus condition, group and ear effects were noticed, however, no age, frequency, or contralateral stimulus type (BBN vs. 1000 Hz) effect could be detected. CONCLUSIONS: Presence of reduced DPOAEs in the autism group does not support the hypothesis that sound hypersensitivity in children with autism may be related to overactive outer hair cells function; rather it may be due to early cochlear dysfunction. Also, sound hypersensitivity in the autism group may be due to abnormality of the efferent auditory pathway as shown by lack of sufficient contralateral suppression. PMID- 22299667 TI - Photodynamic therapy: new treatment for refractory lymphocytic infiltration of the skin. AB - Lymphocytic infiltration of the skin (LIS) is a relatively uncommon skin condition, first described by Jessner and Kanof in 1953. LIS presents mainly on the face, in particular on the cheeks and earlobe, but also on the neck, upper trunk or proximal limbs of middle-aged adults. LIS is often resistant to treatment. Photodynamic therapy (PDT) refers to the process of applying a topical prodrug, such as 5-aminolaevulinic acid (ALA) or methyl 5-aminolaevulinic acid (MAL), followed by irradiation with visible or ultraviolet light. The prodrug is converted by target tissue to photoactive porphyrins, which lead to local tissue destruction when activated by light. We describe a 48-year-old woman with refractory LIS, who was treated with MAL-PDT. PMID- 22299668 TI - PP1 and PP2A phosphatases--cooperating partners in modulating retinoblastoma protein activation. AB - The retinoblastoma/pocket protein family is one of the master regulators of the eukaryotic cell cycle. It includes the retinoblastoma protein (Rb) and the related p107 and p130 proteins. The importance of the Rb pathway for homeostasis and tumour suppression is evident from the fact that inactivating mutations in Rb are frequently associated with many cancers. Rbs regulate the cell cycle by controlling the activity of the E2F family of transcription factors. The activity of Rb proteins themselves is modulated by their phosphorylation status at several Ser/Thr residues: phosphorylation by cyclin-dependent kinases inactivates Rb proteins and positively influences the transcription of genes necessary for cell cycle progression. Although the mechanisms of cyclin-dependent kinase-mediated inactivation of Rb proteins are understood in great detail, our knowledge of the process that counteracts Rb phosphorylation is still quite limited. The present review focuses on the Ser/Thr phosphatases that are responsible for the dephosphorylation and thus activation of Rb proteins. Two major scenarios are considered: (a) when pocket proteins are dephosphorylated during regular cell cycle progression and (b) when rapid dephosphorylation is dictated by external stress or growth inhibitory conditions, such as oxidative stress, UV radiation or other DNA-damaging stimuli, and cell differentiation factors. It transpires that protein phosphatase 1 and protein phosphatase 2A can efficiently modulate pocket protein activity in a highly context-dependent manner and both are tightly regulated by the presence of different regulatory subunits or interacting proteins. PMID- 22299669 TI - Isoproterenol stress test during catheterization of patients with coarctation of the aorta. AB - BACKGROUND: The exercise test is considered useful in selecting high-risk patients with repaired coarctation of the aorta (CoA), but it is difficult to obtain the cooperation of pediatric patients. The present study determines the feasibility of the isoproterenol stress test (IST) among pediatric patients with CoA. METHODS: Thirteen patients with repaired or mild preoperative CoA aged 1-207 (median 13) months underwent 16 IST during cardiac catheterization. Peak-to-peak pressure gradients (PG) over the coarctation site were measured at baseline and at IST. Balloon angioplasty (BAP) was applied to patients with significant stenosis on angiography. RESULTS: The PG between the ascending and the descending aorta was significantly higher at IST than at baseline (20.5 +/- 11.5 vs 5.6 +/- 3.9 mmHg, P < 0.0001). Heart rate, the systolic blood pressure measured at the ascending aorta, and pulse pressure were all significantly higher at IST than at baseline. The PG at IST decreased >10 mmHg in three of six patients after BAP. CONCLUSIONS: Significant pressure gradients over the coarctation site develop at IST in pediatric patients with repaired CoA or in preoperative patients with mild coarctation. PMID- 22299670 TI - The presence of autophagy in mammal cells should be interpreted carefully. PMID- 22299671 TI - The FAS/cd95 promoter single-nucleotide polymorphism -670 A/G and lupus erythematosus. AB - An increased level of circulating nuclear antigens caused by apoptosis is thought to be responsible for the production of autoantibodies in lupus erythematosus (LE). The presentation of these antigens to immunologically competent cells may trigger systemic autoimmunity. The influence of a functional single-nucleotide polymorphism at position -670 in the promoter of the apoptosis gene FAS on susceptibility to autoimmune diseases including systemic LE has been a controversial subject. Although it has not yet been possible to assign any particular allele or genotype to the control of FAS expression, this polymorphism has been described to be associated with several autoimmune diseases including LE. When we compared the FAS -670 A/G genotypes of 107 German patients with LE and those of 96 healthy controls, we found a trend for association between LE and the homozygous A genotype in the patient group. This finding suggests that apoptosis may contribute to development of autoimmune reactions and that FAS function might be relevant for LE. PMID- 22299672 TI - Messages HIV clinicians use in prevention with positives interventions. AB - Prevention with Positives (PwP) is a component of the US HIV prevention strategy that targets HIV-infected persons who are aware of their seropositive status. This paper examines the use of prevention messages by clinical providers during the PwP intervention period of the US Health Resources and Services Administration's Special Projects of National Significance program. Quantitative approaches were used to learn which prevention topics were most discussed and qualitative interviews were also utilized to better understand the clinician perspective in providing prevention counseling. At 12-month follow-up, there was a significant increase in the percent of patients receiving all PwP counseling messages (p<0.01). Providers reported discussing safer sex with 91% of patients when sexually transmitted infection (STI) screening was conducted during a visit, an increase from baseline (83.5%). The percent of providers reporting they regularly explained the risk of superinfection to their clients also increased from 75% at baseline to 90% at 12-month follow up (p<0.001). Qualitative data suggest that providers prioritize individual care over public health approaches to PwP in counseling. Discussing superinfection offered providers a way to discuss HIV prevention from a non-judgmental clinical perspective while focusing on a patient-centered philosophy of care. However, the threat of superinfection may not be the best counseling option. Examples such as STI screening, giving messages to reduce the number of sexual partners and adherence to medication, are more evidence-based approaches to changing HIV transmission risk behavior and may be more important in PwP. Findings suggest that in order for HIV care providers to incorporate HIV prevention discussions into their practice, acceptable approaches to speaking about risk behavior and prevention of HIV transmission must be developed. PMID- 22299673 TI - The effect of HIFA waiver expansions on uninsurance rates in adult populations. AB - RESEARCH OBJECTIVE: To evaluate the effect of the Health Insurance Flexibility and Accountability (HIFA) demonstrations on the rate of uninsured. The policy purpose of the HIFA demonstrations is to encourage "new comprehensive state approaches" that will increase the number of insured. HIFA interventions include changes in benefit packages, eligibility rules for public programs, and state subsidization of private health insurance premiums. Some states emphasized private insurance (premium assistance), whereas others placed greater emphasis on expanded eligibility for public insurance. DATA SOURCES/STUDY SETTING: Data were drawn from the Current Population Survey from 2000 to 2007. The target populations for the HIFA waiver demonstrations consisted of individuals who were eligible for the HIFA waiver demonstrations in demonstration states. STUDY DESIGN: The estimation approach was a probit model using a difference-in differences approach. PRINCIPAL FINDINGS: In states that fully implemented their HIFA waiver, HIFA increased the rate of insurance coverage by 6.4 percentage points on average in the targeted adult population, suggesting that approximately 118,848 adults gained health insurance due to HIFA. Total HIFA adult enrollment in the six states studied was 280,739. The effect size varied by state, with Maine having the largest effect and Illinois the smallest. The results were robust to different specifications of the control group. CONCLUSIONS: Our findings suggest that public insurance initiatives that provide states with flexibility regarding eligibility and plan design are a viable policy approach to reducing uninsurance rates. PMID- 22299674 TI - The Framingham risk score and heart disease in nonalcoholic fatty liver disease. AB - The accuracy of the Framingham risk score (FRS) in identifying patients with nonalcoholic fatty liver disease (NAFLD) at higher 10-year coronary heart disease (CHD) risk remains unknown. We aimed at evaluating both the baseline probability of CHD as predicted by the FRS and the actual long-term occurrence of CHD in NAFLD patients. This was a longitudinal study of a community-based cohort. A total of 309 NAFLD patients were followed up for 11.5 +/- 4.1 years (total 3554 person-years). The overall calculated 10-year CHD risk was significantly higher in the NAFLD cohort than the absolute CHD risk predicted by the FRS for persons of the same age and gender (10.9 +/- 9.3% vs. 9.9 +/- 5.9%, respectively, P < 0.0001), and higher in men than women (12.6 +/- 10.3% vs. 9.6 +/- 8.1%, respectively, P = 0.006). New onset CHD occurred in 34 patients (11% vs. 10.9% predicted at baseline, P = NS), whereas 279 (89%) patients did not develop CHD. Using multivariable analysis, the FRS was the only variable significantly associated with new onset CHD (OR = 1.13, 95% CI = 1.05-1.21; P = 0.001). A FRS cut-point of 11 in women, and 6 in men had a sensitivity of 80% and 74%, respectively, and a negative predictive value of 97% and 93% respectively. NAFLD patients have a higher 10-year CHD risk than the general population of the same age and gender. The FRS accurately predicts the higher 10-year CHD risk in NAFLD patients, and helps identify those patients expected to derive the most benefit from early intervention to prevent CHD events. PMID- 22299675 TI - Activation of C-O and C-C bonds and formation of novel HAlOH-ether complexes: an EPR study of the reaction of ground-state Al atoms with methylethyl ether and diethyl ether. AB - Reaction mixtures, containing Al atoms and methylethyl ether (MEE) or diethyl ether (DEE) in an adamantane matrix, were prepared with the aid of a metal-atom reactor known as a rotating cryostat. The EPR spectra of the resulting products were recorded from 77-260 K, at 10 K intervals. Al atoms were found to insert into methyl-O, ethyl-O, and C-C bonds to form CH(3)AlOCH(2)CH(3), CH(3)OAlCH(2)CH(3), and CH(3)OCH(2)AlCH(3), respectively, in the case of MEE while DEE produced CH(3)CH(2)AlOCH(2)CH(3) and CH(3)AlCH(2)OCH(2)CH(3), respectively. From the intensity of the transition lines attributed to the Al atom C-O insertion products of MEE, insertion into the methyl-O bond is preferred. The Al hyperfine interaction (hfi) extracted from the EPR spectra of the C-O insertion products was greater than that of the C-C insertion products, that is, 5.4% greater for the DEE system and 7% greater for the MEE system. The increase in Al hfi is thought to arise from the increased electron-withdrawing ability of the substituents bonded to Al. Besides HAlOH, resulting from the reaction of Al atoms with adventitious water, novel mixed HAlOH:MEE and HAlOH:DEE complexes were identified with the aid of isotopic studies involving H(2)(17)O and D(2)O. The Al and H hfi of HAlOH were found to decrease upon complex formation. These findings are consistent with the nuclear hfi calculated using a density functional theory (DFT) method with close agreement between theory and experiment occurring at the B3LYP level using a 6-311+G(2df,p) basis set. PMID- 22299676 TI - Clinical signs of uveitis associated with latent tuberculosis. AB - BACKGROUND: To identify the clinical ocular signs of uveitis associated with latent tuberculosis. DESIGN: Retrospective case-control study. PARTICIPANTS: Consecutive patients from Singapore National Eye Centre Uveitis over 9 years. Sixty-two patients with uveitis associated with latent tuberculosis were compared with 72 matched controls diagnosed with other known uveitides. METHODS: Patients were categorized as: (A) predominantly anterior segment inflammation (anterior uveitides) and (B) predominantly posterior segment inflammation (intermediate, posterior or pan-uveitides). The diagnostic performance of combining these clinical signs with investigations such as interferon-gamma release assay positivity and chest X-ray results suggestive of pulmonary tuberculosis was done using area under the receiver operator characteristic curve. MAIN OUTCOME MEASURES: Sensitivity, specificity and likelihood of association with tuberculosis of various clinical signs. RESULTS: Extensive posterior synechiae and concomitant anterior scleritis in Group A; low-grade anterior chamber activity, retinal phlebitis and severe vitritis in Group B were significantly associated with latent tuberculosis. Combining these clinical signs with a positive interferon-gamma release assay and tuberculin skin test improved the diagnostic performance in both groups (area under the receiver operator characteristic curve for Group A = 0.779; Group B = 0.789). CONCLUSION: Patients with a combination of suggestive clinical signs with positive interferon gamma release assay and tuberculin skin test are more likely to be accurately diagnosed with uveitis associated with latent tuberculosis, which responds to anti-tuberculosis therapy. PMID- 22299677 TI - Regioselective ring expansion of 2,4-diiminoazetidines via cleavage of C-N and C(sp3)-H bonds: efficient construction of 2,3-dihydropyrimidinesulfonamides. AB - A highly regioselective base-mediated ring expansion of 2,4-diiminoazetidines via cleavage of C-N and C(sp(3))-H bonds is achieved for the first time to afford efficiently 2,3-dihydropyrimidinesulfonamides. The mechanism of the ring expansion via tandem 4pi electrocyclic ring-opening/1,5-H shift/6pi electrocyclic ring-closing is well confirmed by the trapping experiments of two key intermediates and deuterium labeling studies. PMID- 22299678 TI - Poly(A)-binding protein increases the binding affinity and kinetic rates of interaction of viral protein linked to genome with translation initiation factors eIFiso4F and eIFiso4F.4B complex. AB - VPg of turnip mosaic virus (TuMV) was previously shown to interact with translation initiation factor eIFiso4F and play an important role in mRNA translation [Khan, M. A., et al. (2008) J. Biol. Chem.283, 1340-1349]. VPg competed with cap analogue for eIFiso4F binding and competitively inhibited cap dependent translation and enhanced cap-independent translation to give viral RNA a significant competitive advantage. To gain further insight into the cap independent process of initiation of protein synthesis, we examined the effect of PABP and/or eIF4B on the equilibrium and kinetics of binding of VPg to eIFiso4F. Equilibrium data showed the addition of PABP and/or eIF4B to eIFiso4F increased the binding affinity for VPg (K(d) = 24.3 +/- 1.6 nM) as compared to that with eIFiso4F alone (K(d) = 81.3 +/- 0.2.4 nM). Thermodynamic parameters showed that binding of VPg to eIFiso4F was enthalpy-driven and entropy-favorable with the addition of PABP and/or eIF4B. PABP and eIF4B decreased the entropic contribution by 67% for binding of VPg to eIFiso4F. The decrease in entropy involved in the formation of the eIFiso4F.4B.PABP-VPg complex suggested weakened hydrophobic interactions for complex formation and an overall conformational change. The kinetic studies of eIFiso4F with VPg in the presence of PABP and eIF4B show 3 fold faster association (k(2) = 182 +/- 9.0 s(-1)) compared to that with eIFiso4F alone (k(2) = 69.0 +/- 1.5 s(-1)) . The dissociation rate was 3-fold slower (k( 2) = 6.5 +/- 0.43 s(-1)) for eIFiso4F with VPg in the presence of PABP and eIF4B (k(-2) = 19.0 +/- 0.9 s(-1)). The addition of PABP and eIF4B decreased the activation energy of eIFiso4F with VPg from 81.0 +/- 3.0 to 44.0 +/- 2.4 kJ/mol. This suggests that the presence of both proteins leads to a rapid, stable complex, which serves to sequester initiation factors. PMID- 22299680 TI - Guest Editorial: Cost effective environmental goals. PMID- 22299681 TI - Pollutants and human reproduction. PMID- 22299682 TI - Response by author. PMID- 22299684 TI - Currents. PMID- 22299683 TI - Cost of air pollution control. PMID- 22299685 TI - Outlook. PMID- 22299687 TI - Long-term nuclear options. PMID- 22299686 TI - Leasing of outer Contenental Shelf. PMID- 22299688 TI - The role of science in EPA decision making. PMID- 22299689 TI - Fingerprinting pollutant discharges from synfuels plants. PMID- 22299690 TI - Acidity of atmospheric aerosols. PMID- 22299691 TI - Kinetics for the aquatic environment. PMID- 22299692 TI - ES Products. PMID- 22299693 TI - ES Literature. PMID- 22299694 TI - ES Books. PMID- 22299695 TI - Meeting guide/directory/reader svs. PMID- 22299696 TI - Chemical demulsification of aged, crude oil emulsions. PMID- 22299697 TI - Adsorption of organic compounds from dilute aqueous solutions onto the external surface of type A zeolite. PMID- 22299698 TI - Characterization of airborne heavy metals within a primary zinc-lead smelting works. PMID- 22299699 TI - Copper(II)- and cadmium(II)-binding abilities of some New Hampshire freshwaters determined by dialysis titration. PMID- 22299700 TI - Structure and evolution of fugitive particles from a copper smelter. PMID- 22299701 TI - Identification and determination of individual tetraalkyllead species in air. PMID- 22299702 TI - Adsorption of dissolved organics in lake water by aluminum oxide. Effect of molecular weight. PMID- 22299704 TI - Trace pollutant concentrations in a multiday smog episode in the California South Coast Air Basin by long path length Fourier transform infrared spectroscopy. PMID- 22299703 TI - Thermal decomposition rate constant of peroxybenzoyl nitrate in the gas phase. PMID- 22299705 TI - Organic compounds found near dump sites in Niagara Falls, New York. PMID- 22299706 TI - Sodium alteration of chlorine equilibriums. Quantitative description. PMID- 22299707 TI - Androgenic suppression combined with radiotherapy for the treatment of prostate adenocarcinoma: a systematic review. AB - BACKGROUND: Locally advanced prostate cancer is often associated with elevated recurrence rates. Despite the modest response observed, external-beam radiotherapy has been the preferred treatment for this condition. More recent evidence from randomised trials has demonstrated clinical benefit with the combined use of androgen suppression in such cases. The aim of this meta-analysis is to compare the combination of distinct hormone therapy modalities versus radiotherapy alone for overall survival, disease-free survival and toxicity. METHODS: Databases (MEDLINE, EMBASE, LILACS, Cochrane databases and ClinicalTrials.gov) were scanned for randomised clinical trials involving radiotherapy with or without androgen suppression in local prostate cancer. The search strategy included articles published until October 2011. The studies were examined and the data of interest were plotted for meta-analysis. Survival outcomes were reported as a hazard ratio with corresponding 95% confidence intervals. RESULTS: Data from ten trials published from 1988 to 2011 were included, comprising 6555 patients. There was a statistically significant advantage to the use of androgen suppression, in terms of both overall survival and disease free survival, when compared to radiotherapy alone. The use of long term goserelin (up to three years) was the strategy providing the higher magnitude of clinical benefit. In contrast to goserelin, there were no trials evaluating the use of other luteinizing hormone-releasing hormone (LHRH) analogues as monotherapy. Complete hormonal blockade was not shown to be superior to goserelin monotherapy. CONCLUSIONS: Based on the findings of this systematic review, the evidence supports the use of androgen suppression with goserelin monotherapy as the standard treatment for patients with prostate cancer treated with radiotherapy, which are at high risk of recurrence or metastases. PMID- 22299708 TI - Assessing treatment-selection markers using a potential outcomes framework. AB - Treatment-selection markers are biological molecules or patient characteristics associated with one's response to treatment. They can be used to predict treatment effects for individual subjects and subsequently help deliver treatment to those most likely to benefit from it. Statistical tools are needed to evaluate a marker's capacity to help with treatment selection. The commonly adopted criterion for a good treatment-selection marker has been the interaction between marker and treatment. While a strong interaction is important, it is, however, not sufficient for good marker performance. In this article, we develop novel measures for assessing a continuous treatment-selection marker, based on a potential outcomes framework. Under a set of assumptions, we derive the optimal decision rule based on the marker to classify individuals according to treatment benefit, and characterize the marker's performance using the corresponding classification accuracy as well as the overall distribution of the classifier. We develop a constrained maximum-likelihood method for estimation and testing in a randomized trial setting. Simulation studies are conducted to demonstrate the performance of our methods. Finally, we illustrate the methods using an HIV vaccine trial where we explore the value of the level of preexisting immunity to adenovirus serotype 5 for predicting a vaccine-induced increase in the risk of HIV acquisition. PMID- 22299709 TI - Discrimination, crypticity, and incipient taxa in entamoeba. AB - Persistent difficulties in resolving clear lineages in diverging populations of prokaryotes or unicellular eukaryotes (protistan polyphyletic groups) are challenging the classical species concept. Although multiple integrated approaches would render holistic taxonomies, most phylogenetic studies are still based on single-gene or morphological traits. Such methodologies conceal natural lineages, which are considered "cryptic." The concept of species is considered artificial and inadequate to define natural populations. Social organisms display differential behaviors toward kin than to nonrelated individuals. In "social" microbes, kin discrimination has been used to help resolve crypticity. Aggregative behavior could be explored in a nonsocial protist to define phylogenetic varieties that are considered "cryptic." Two Entamoeba invadens strains, IP-1 and VK-1:NS are considered close populations of the same "species." This study demonstrates that IP-1 and VK-1:NS trophozoites aggregate only with alike members and discriminate members of different strains based on behavioral and chemical signals. Combined morphological, behavioral/chemical, and ecological studies could improve Archamoebae phylogenies and define cryptic varieties. Evolutionary processes in which selection acted continuously and cumulatively on ancestors of Entamoeba populations gave rise to chemical and behavioral signals that allowed individuals to discriminate nonpopulation members and, gradually, to the emergence of new lineages; alternative views that claim a "Designer" or "Creator" as responsible for protistan diversity are unfounded. PMID- 22299710 TI - Bacterial resistance and impetigo treatment trends: a review. AB - Impetigo is a common cutaneous infection that is especially prevalent in children. The prevalence of colonization and infection with resistant strains is continually increasing, forcing clinicians to reevaluate treatment strategies. Newer topical agents are effective in treating infections with resistant strains and may help minimize resistance and adverse effects from systemic agents. Use of topical disinfectants to decrease colonization is an important adjunctive measure. Physicians should be aware of local resistance patterns in impetigo to help guide therapy. PMID- 22299711 TI - Lys(203) and Lys(382) are essential for the proteasomal degradation of BACE1. AB - Amyloid beta protein (Abeta) is the primary component of senile plaques in Alzheimer's disease brains and its aggregate form is neurotoxic. Abeta is generated through proteolysis of beta-amyloid precursor protein (APP) by two proteases: beta-secretase and gamma-secretase. BACE1, the beta-secretase in vivo and the key rate-limiting enzyme that initiates the formation of Abeta, is an attractive drug target for AD therapy. Our previous study demonstrated that BACE1 is ubiquitinated and its degradation and effect on APP cleaving process are mediated by the ubiquitin-proteasome pathway. However, the specific underlying mechanism is still not well defined. In present study, we determined the specific binding sites responsible for the proteasomal degradation of BACE1. Ten fragments of human BACE1 cDNA with each of them containing 1 to 3 Lys codons were cloned, and HEK293 cells transfected with these recombinant plasmids were treated with specific proteasome inhibitor lactacystin. The protein levels of fragment-3 (Pro(149)-Leu(180)), -4 (IIe(179)-Ser(230)) and -8 (Met(349)-Arg(400)) were significantly increased by lactacystin treatment, and immunocytochemical staining results showed that fragment-3, -4 and -8 proteins were colocalized with ubiquitin. Site-directed mutagenesis at Lys(203) and Lys(382) of BACE1 abolished the proteasomal degradation of BACE1 and affected APP processing at beta site and Abeta production. Taken together, our study demonstrated that BACE1 Lys(203) and Lys(382) are essential for its proteasomal degradation, and the results may advance our understanding of regulation of BACE1 and APP processing by the ubiquitin proteasome system in AD pathogenesis and shed new insights on its pharmaceutical potential. PMID- 22299712 TI - The role of TMP21 in trafficking and amyloid-beta precursor protein (APP) processing in Alzheimer's disease. AB - Alzheimer's Disease (AD) is the most common neurodegenerative disorder leading to dementia. A major neuropathological hallmark of AD is the deposition of amyloid beta protein (Abeta) in the form of neuritic plaques. Abeta is formed by the sequential cleavage of amyloid-beta precursor protein (APP) by beta- and gamma secretase. It was recently suggested that TMP21 is a novel member of the gamma secretase complex which negatively regulates APP cleavage at the gamma-site, but does not affect cleavage of APP or Notch at the -site . In vitro knockdown of TMP21 increases Abeta production and AD patients have less TMP21 expressed in their brains, suggesting that a deficiency in TMP21 may exacerbate AD pathology. TMP21 is most commonly known for its role in vesicle trafficking. Here we present the most recent research on TMP21 in relation to AD, including TMP21's roles in the modulation of gamma-secretase activity and protein trafficking. PMID- 22299713 TI - Antiapoptotic and antioxidant effects of GSPE in preventing cyclosporine A induced cardiotoxicity. AB - OBJECTIVES: Cyclosporine A (CsA) is an immunosuppressive drug, but cardiotoxicity is one of its side effects. Free oxygen radical damage and apoptosis are considered to be responsible for CsA-induced cardiotoxicity. Grape seed proanthocyanidin extract (GSPE) displays antioxidant and antiapoptotic activities. Therefore, we aimed to evaluate the effect of GSPE on CsA-induced cardiotoxicity. MATERIALS AND METHODS: Twenty-four rats were divided into four groups, with six rats in each group. CsA-induced nephropathy was induced by administration of 25 mg/kg CsA. The experiment was discontinued on day 21, and total oxidant system (TOS), total antioxidant system (TAS), oxidative stress index (OSI), and malondialdehyde (MDA) were measured in order to evaluate oxidative damage to the heart tissue. In addition to cardiac histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. RESULTS: The CsA group showed a significant increase in TOS, OSI, MDA, cardiac histopathological score, and apoptotic index (AI); in the CsA + GSPE group, OSI, MDA, cardiac histopathological score, and AI decreased significantly, and TAS levels showed a significant increase. CONCLUSION: In this study, we demonstrated for the first time in the literature that GSPE prevents CsA cardiotoxicity and that this effect can be achieved by antiapoptotic and antioxidant activities. PMID- 22299714 TI - Effect of quetiapine and norquetiapine on anxiety and depression in major psychoses using a pharmacokinetic approach: a prospective observational study. AB - BACKGROUND: Quetiapine apparently differs from other antipsychotic drugs in terms of its antidepressant activity and efficacy in bipolar depression. The mechanism of this activity is unknown although it may be mediated by its metabolite N desalkylquetiapine (norquetiapine). OBJECTIVE: The aim of the study was to analyse the relationships between quetiapine and norquetiapine plasma concentrations and clinical improvement in depressive and anxious symptoms. METHODS: This was a prospective observational study. Recruited patients were evaluated during a clinical post-acute phase. Patients were recruited from patients hospitalized in the Psychiatric Department of Ospedale Maggiore Policlinico of Milan, Italy. After discharge they were followed-up as outpatients. The study involved 41 outpatients (23 males, 18 females; age >18 years) diagnosed as affected by schizophrenia (17 patients), borderline personality disorder (eight patients) or bipolar depression (16 patients) on the basis of the Diagnostic and Statistical Manual of Mental Disorders, fourth text revision (DSM-IV-TR) criteria. Patients were prescribed 50-800 mg of quetiapine (Seroquel(r)). Patients were evaluated after discharge from the psychiatric department (baseline, T0), after 15 days (T1) and after 3 months (T2) using the Brief Psychiatry Rating Scale (BPRS) with particular reference to the dimensions of depression (items 5, 9 and 13) and anxiety (items 1, 2 and 6). Plasma quetiapine and norquetiapine concentrations were determined by means of high performance liquid chromatography at T2. RESULTS: There was a significant improvement in the mean BPRS total score, as well as in the dimensions of anxiety and depression. The bipolar patients only showed a significant curvilinear relationship described by a second-order polynomial model between the plasma norquetiapine/quetiapine concentration ratio and the improvement in depression at T2. There was a significant negative linear correlation between the norquetiapine/quetiapine ratio and anxiety in all of the patients. CONCLUSION: The results of this study confirm the efficacy of quetiapine on both anxious and depressive symptoms. Norquetiapine has a specific effect on anxiety and depressive symptoms, showing a correlation between plasma concentrations and clinical efficacy only in patients with bipolar depression. PMID- 22299715 TI - Safety and tolerability of bismuthyl ecabet suspension, a novel anti-ulcer agent, following single and multiple oral dose administration in healthy Chinese subjects. AB - BACKGROUND: Bismuthyl ecabet is a combination of sulfodehydroabietic acid and bismuth, which forms a new type of salt that is useful in treating peptic ulcers and gastritis. OBJECTIVE: This study was designed to assess the safety and tolerability of bismuthyl ecabet suspension in healthy Chinese subjects. METHODS: For the study 77 volunteers were randomized into single- or multiple-dose groups for oral administration of bismuthyl ecabet 200-1600 mg once daily or 1200 mg twice daily for 7 days. Safety and tolerability were assessed by adverse events, physical examination and serum biochemistry. RESULTS: In both the single- and multiple-dose studies, no severe adverse events were observed in any of the volunteers. The main adverse events caused by the drug in single-dose groups were an increase in serum alanine transaminase (ALT), gamma-glutamyl transpeptidase, blood urea nitrogen, total bilirubin and skin rash. The numbers of adverse events judged to be possibly related to the drug were 2/18 in the 400 mg, 2/18 in the 800 mg, 1/8 in the 1200 mg, and none in the 200 or 1600 mg dose groups. In the multiple-dose studies, an increased serum ALT and aspartate transaminase (AST) was found in one subject after 7 days of administration of the drug. All serum biochemistry returned to normal levels and skin rash resolved after 7 days without any special treatment. CONCLUSION: Bismuthyl ecabet was shown to be safe and well tolerated in healthy Chinese subjects. The oral dosing regimen selected for subsequent phase II/III clinical trials was 800 mg twice daily. PMID- 22299716 TI - Immunotoxicologic effects of cyclosporine on tumor progression in models of squamous cell carcinoma and B-cell lymphoma in C3H mice. AB - Many immunosuppressive drugs are associated with an increased risk of neoplasia, principally non-melanoma skin cancers and B-cell lymphomas. However, only 6 of the 13 immunosuppressive drugs tested in 2 year bioassays increased the incidence of neoplasia. For example, the 2-year bioassays conducted with cyclosporine (CSA), an International Agency for Research on Cancer (IARC) Group 1 human carcinogen, were negative. The purpose of these investigations was to use transplanted tumor models in immunocompetent, syngeneic mice to gain insight into the failure of the 2-year bioassay to show an increased incidence of neoplasia with CSA. C3H HeN mice were used in a battery of assays with a transplanted squamous cell carcinoma (SCC VII cells) or a B-cell, lymphoma (38C13 cells) cells to study effects of CSA on local growth and metastases, experimental metastases, and progression of established metastases. Mice received CSA twice weekly by subcutaneous (SC) injection at doses of 0.5, 5, or 50 mg/kg; controls received the CSA vehicle. CSA had a modest inhibitory effect on SC tumors initiated by 38C13 cells and on intramuscular tumors initiated by SCC VII cells. CSA also decreased the number of lung colonies and decreased the size, growth fraction and vascularity of established lung metastases initiated by SCC VII cells. In contrast, CSA increased progressive growth of metastases to the sentinel lymph node from an intramuscular SCC VII tumor, but had no effect cellular traffic to the node. In conclusion, CSA at doses up to 50 mg/kg did not facilitate tumor progression and it partially inhibited tumor growth, suggesting that suppression of tumor progression may partially explain the failure of CSA to act as a carcinogen in 2 year bioassays. PMID- 22299717 TI - Effects of nanoparticle-rich diesel exhaust particles on IL-17 production in vitro. AB - It has been shown that pulmonary exposure to diesel exhaust particles (DEP) disrupt immune systems, presenting as exacerbating effects on allergic manifestations (e.g., allergic asthma). To date, the impact of nano-level DEP on health has not been fully elucidated. Our institute (the National Institute for Environmental Studies) established an 'environmental nanoparticle exposure system applied in animals' in 2005 and, since then, the health effects of exposures to these types of agents have been explored. The present study was designed to investigate the in vitro effects of nanoparticle-rich DEP (NRDEP) on primary splenocytes from atopy-prone hosts. NC/Nga mouse-derived splenic mononuclear cells were co-cultured with NRDEP (0-50 ug/ml); thereafter, cell viability/proliferation was evaluated via a WST-1 assay, production/release of interleukin (IL)-17A in the culture supernatants by ELISA, and expression of RORgammat (retinoic acid-related orphan receptor-gammat) in cell lysates by Western blot analyses. The results indicated that NRDEP reduced cell viability/proliferation in a dose-related manner-significantly so at a level of 50 ug/ml NRDEP. In contrast, up to 10 ug NRDEP/ml increased RORgammat expression in the splenocytes and subsequent IL-17A production/release by the cells in a dose-dependent manner with an overall trend (with significance vs 1 ug NRDEP/ml and 10 ug NRDEP/ml for IL-17A); 50 ug NRDEP/ml tended to inhibit the transcription factor expression and cytokine production/release. These results suggest that NRDEP can activate naive splenic mononuclear cells from atopy-prone animals in terms of RORgammat and IL-17A induction (T(H)17 response). PMID- 22299718 TI - A summary of meeting proceedings for 'Measuring immune responses in non-human primates for drug development-opportunities and challenges for predicting human efficacy and immunotoxicity'. PMID- 22299719 TI - Amlodipine-induced linear IgA disease. AB - A 58-year-old woman presented with a 3-week history of a pruritic rash, which had started a week after commencing treatment with amlodipine. On physical examination, large, well-demarcated erythematous plaques, surrounded by small clusters of clear vesicles, were seen on the patient's torso. Subepidermal blisters with neutrophils and eosinophils were seen in a skin biopsy, and direct immunofluorescence showed deposition of IgA along the basement membrane, in keeping with a diagnosis of linear IgA dermatosis (LAD). Amlodipine was discontinued, and the patient was started on prednisolone 30 mg, supplemented shortly afterwards by dapsone, which resulted in prompt resolution of the rash. Only a few cases of drug-induced LAD have been reported, mostly in association with vancomycin. To our knowledge, this is the first reported case precipitated by amlodipine. PMID- 22299720 TI - Ceramide profile in hypohidrotic ectodermal dysplasia. AB - BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) is a rare genetic disease. The clinical presentation includes lack of sweating ability, and an often widely spread dermatitis resembling atopic dermatitis (AD). In AD, the skin-barrier defect is partly ascribed to the altered lipid profile in the stratum corneum and partly to mutations of the filaggrin genes. To our knowledge, no data are available about the epidermal lipid profile of HED. AIM: To compare the ceramide profile for patients with HED and AD. METHODS: The ceramide profile and ceramide/cholesterol ratio were compared between patients with HED (n = 7) and patients with AD (n = 21), using cyanoacrylate to take biopsy samples from the stratum corneum. Lipids were extracted from the biopsies and analysed using high performance thin-layer chromatography. RESULTS: The lipid profiles of HED and AD were similar in distribution, apart from ceramide 1, which was significantly higher in HED (P = 0.04). CONCLUSIONS: The increased ceramide 1 level found in HED compared with AD is known to play a role in the structure of the lipid bilayers. However, further studies are needed to identify the functional significance of these observations and thereby elucidate differences in the skin barrier between HED and AD. PMID- 22299721 TI - Caring for the caregiver: evaluation of support groups for guardians of orphans and vulnerable children in Kenya. AB - HIV and AIDS have altered the context in which millions of children in sub Saharan Africa are raised. Many are under the care of a widowed or ill parent, and others are residing with their extended family. Caregivers of orphans and other vulnerable children (OVC) face a variety of stressors that may adversely affect children. This study explores potential benefits of caregivers' membership in support groups on their own psychosocial wellbeing, and on the treatment and psychosocial well-being of OVC aged 8-14 under their care. A post-test study design comparing members and non-members was applied, drawing upon random samples of current and prospective beneficiaries from a rural community in Kenya. With up to two children per caregiver eligible for study inclusion, the sample comprised 766 caregivers and 1028 children. Three-quarters of children had lost at least one parent. Nearly 90% were cared for by a female, often their natural mother or grandmother. Half of the caregivers were widowed and one-fifth had a chronic illness. Over one-third of caregivers were members of support groups, more commonly female caregivers. Regression analyses assessed the effect of support group membership after controlling for household, caregiver and child characteristics. Members reported less social marginalization, better family functioning and more positive feelings towards the children in their care than nonmembers. Children with caregivers in support groups exhibited fewer behavioral problems, higher rates of prosocial behavior and reported lower incidence of abuse from adults in their household. The psychological state of caregivers, however, was not associated with support group membership. Results underscore that quality care of vulnerable children hinges on interventions that address the psychosocial challenges facing their caregivers. PMID- 22299722 TI - Organizational characteristics of high- and low-performing anticoagulation clinics in the Veterans Health Administration. AB - OBJECTIVE: Anticoagulation clinics (ACCs) can improve anticoagulation control and prevent adverse events. However, ACCs vary widely in their performance on anticoagulation control. Our objective was to compare the organization and management of top-performing with that of bottom-performing ACCs. DATA SOURCES/STUDY SETTING: Three high outlier and three low outlier ACCs in the Veterans Health Administration (VA). STUDY DESIGN: Site visits with qualitative data collection and analysis. DATA COLLECTION/EXTRACTION METHODS: We conducted semi-structured interviews with ACC staff regarding work flow, staffing, organization, and quality assurance efforts. We also observed ACC operations and collected documents, such as the clinic protocol. We used grounded thematic analysis to examine site-level factors associated with high and low outlier status. PRINCIPAL FINDINGS: High outlier sites were characterized by (1) adequate (pharmacist) staffing and effective use of (nonpharmacist) support personnel; (2) innovation to standardize clinical practice around evidence-based guidelines; (3) the presence of a quality champion for the ACC; (4) higher staff qualifications; (5) a climate of ongoing group learning; and (6) internal efforts to measure performance. Although high outliers had all of these features, no low outlier had more than two of them. CONCLUSIONS: The top-performing ACCs in the VA system shared six relatively recognizable characteristics. Efforts to improve performance should focus on these domains. PMID- 22299723 TI - Counting small hypointense spots confounds the quantification of functional islet mass based on islet MRI. AB - Iron-containing fragmented islets or free iron released from dying cells could confound the interpretation of MRI of iron nanoparticle-labeled islets. Exclusion of small hypointense spots could be a useful strategy to avoid such artifact. We investigated whether this strategy could improve the estimation of functioning islet mass after islet transplantation. Using a rat syngeneic intraportal islet transplantation model, we quantitatively assessed the relationships between total area, number of hypointense spots on MRI that belong to each size quartile and glycemic control of the recipients. The total area of hypointense spots on MRI was greater in the recipients that achieved diabetes reversal (p = 0.002), whereas the total number of hypointense spots was not different (p = 0.757). Exclusion of small hypointense spots improved the association between the number of hypointense spots and the blood glucose level of the recipients (p < 0.001). Ex-vivo imaging and histologic study confirmed that some small hypointense spots represent the phagocytosed free iron. Exclusion of small hypointense spots improved the quantification of the functional islet mass based on islet MRI. This would be a useful principle in the development of an algorithm to estimate functioning islet mass based on islet MRI. PMID- 22299724 TI - Electron affinities of uracil: microsolvation effects and polarizable continuum model. AB - We present adiabatic electron affinities (AEAs) and the vertical detachment energies (VDEs) of the uracil molecule interacting with one to five water molecules. Credibility of MP2 and DFT/B3LYP calculations is supported by comparison with available benchmark CCSD(T) data. AEAs and VDEs obtained by MP2 and DFT/B3LYP methods copy trends of benchmark CCSD(T) results for the free uracil and uracil-water complexes in the gas phase being by 0.20 - 0.28 eV higher than CCSD(T) values depending on the particular structure of the complex. AEAs and VDEs from MP2 are underestimated by 0.09-0.15 eV. For the free uracil and uracil-(H(2)O)(n) (n = 1,2,3,5) complexes, we also consider the polarizable continuum model (PCM) and discuss the importance of the microsolvation when combined with PCM. AEAs and VDEs of uracil and uracil-water complexes enhance rapidly with increasing relative dielectric constant (epsilon) of the solvent. Highest AEAs and VDEs of the U(H(2)O)(5) complexes from B3LYP with epsilon = 78.4 are 2.03 and 2.81 eV, respectively, utilizing the correction from CCSD(T). Specific structural features of the microsolvated uracil-(H(2)O)(n) complexes and their anions are preserved also upon considering PCM in calculations of AEAs and VDEs. PMID- 22299725 TI - Do prescription monitoring programs impact state trends in opioid abuse/misuse? AB - OBJECTIVE: Prescription monitoring programs (PMPs) are statewide databases containing prescriber and patient-level prescription data on select drugs of abuse. These databases are used by medical professionals or law enforcement officials to identify patients with prescription drug use patterns indicative of abuse or providers engaging in illegal activities. Most states have implemented PMPs in an attempt to curb prescription drug abuse and diversion. However, assessment of their impact on drug abuse is only beginning. This study aimed to evaluate the relationship between PMPs and opioid misuse over time in two drug abuse surveillance data sources. METHODS: Data from the RADARS(r) System Poison Center and Opioid Treatment surveillance databases were used to obtain measures of abuse and misuse of opioids. Repeated measures negative binomial regression was applied to quarterly surveillance data (from 2003 to mid-2009) to estimate and compare opioid abuse and misuse trends. PMP presence was modeled as a time varying covariate for each state. RESULTS: Results support an association between PMPs and mitigated opioid abuse and misuse trends. Without a PMP in place, Poison Center intentional exposures increased, on average, 1.9% per quarter, whereas opioid intentional exposures increase 0.2% (P = 0.036) per quarter with a PMP in place. Opioid treatment admissions increase, on average, 4.9% per quarter in states without a PMP vs 2.6% (P = 0.058) in states with a PMP. In addition to the time trend, population and a measure of drug availability were also significant predictors. A secondary analysis that classified PMP based upon ideal characteristic showed consistent though not significant results. CONCLUSIONS: Two observational data sources offer preliminary support that PMPs are effective. Future efforts should evaluate what PMP characteristics are most effective and which opioids are most impacted. PMID- 22299726 TI - Glaucoma in Timor-Leste: an unmet need in diagnosis and treatment. PMID- 22299730 TI - Editorial. A significant risk. PMID- 22299728 TI - Growth factor-associated graft-versus-host disease and mortality 10 years after allogeneic bone marrow transplantation. AB - This study analysed the effects of growth factor on outcome after haematopoietic stem-cell transplantation (HSCT) with >9 years follow-up. Of 1887 adult patients with acute leukaemia who received bone marrow from human leucocyte antigen (HLA) identical siblings and were treated with myeloablative conditioning, 459 (24%) were treated with growth factor. Growth factor hastened engraftment of neutrophils (P < 0.0001), but reduced platelet counts (P = 0.0002). Graft-versus host disease (GVHD)-free survival (no acute GVHD grade II-IV or chronic GVHD) at 10 years was 12 +/- 2% (+/-SE) in the growth factor group, as opposed to 17 +/- 2% in the controls [hazard ratio (HR) 0.81, P = 0.001]. Similar differences in GVHD-free survival were seen in patients with or without conditioning with total body irradiation (TBI). Non-relapse mortality (NRM) was higher in the growth factor group irrespective of whether or not TBI conditioning was included [HR = 1.48; 95% confidence interval (CI): 1.15-1.9; P = 0.002; HR = 1.59; 95% CI: 1.07 2.37; P = 0.02, respectively]. Both groups had similar probabilities of leukaemic relapse (HR = 0.96; 95% CI: 0.78-1.18; P = 0.71). Leukaemia-free survival (LFS) at 10 years was 35 +/- 2% in those receiving growth factor prophylaxis, as opposed to 44 +/- 1% in the controls (HR = 0.70; 95% CI: 0.60-0.82; P = 0.00001). Prophylaxis with growth factor increases the risk of GVHD, does not affect relapse, increases NRM and reduces LFS > 10 years after HSCT, regardless of conditioning with TBI. PMID- 22299731 TI - Letters. Activated carbon use. PMID- 22299732 TI - Letters. Mine waters. PMID- 22299733 TI - Letters. NCR associateships. PMID- 22299735 TI - Outlook. PMID- 22299734 TI - Currents. PMID- 22299736 TI - Regulatory Alert: Reagan's Regulatory Reform. PMID- 22299737 TI - Critical Review. The effect of environmental pollutants on human reproduction, including birth defects. PMID- 22299738 TI - ES Products. PMID- 22299739 TI - ES Literature. PMID- 22299741 TI - Characterization of soluble and colloidal phase metal complexes in river water by ultrafiltration. A mass-balance approach. PMID- 22299740 TI - ES Books. PMID- 22299742 TI - Photochemical ozone formation in the irradiation of ambient air samples by using a mobile smog chamber. PMID- 22299743 TI - Photochemical reactivity and ozone formation in 1-olefin-nitrogen oxide-air systems. PMID- 22299744 TI - Chemical mass accounting of urban aerosol. PMID- 22299745 TI - A .beta.-gage method applied to aerosol samples. PMID- 22299746 TI - Automatic particulate sulfur measurements with a dichotomous sampler and on-line x-ray fluorescence analysis. PMID- 22299747 TI - Use of lead isotopes in soils to identify the source of lead contamination near Adelaide, South Australia. PMID- 22299748 TI - Alkylpyridines in surface waters, groundwaters, and subsoils of a drainage located adjacent to an oil shale facility. PMID- 22299749 TI - Evaluation of Tenax-GC and XAD-2 as polymer adsorbents for sampling fossil fuel combustion products containing nitrogen oxides. PMID- 22299750 TI - Modeling the flux of atmospheric polychlorinated biphenyls across the air/water interface. PMID- 22299751 TI - Comparison of automated segmented-flow and discrete analyzers for the determination of nutrients in water. PMID- 22299752 TI - Automobile Traffic and Lung Cancer. An update on Blumer's Report. PMID- 22299753 TI - Solubility behavior of three aromatic hydrocarbons in distilled water and natural seawater. PMID- 22299754 TI - Assessing survival in widowers, and controls - a nationwide, six- to nine-year follow-up. AB - BACKGROUND: The aim of this study was to assess if widowers had an increased mortality rate during the first 6 to 9 years after the death of their wife, compared initially to an age-matched control group and also compared to the general population of Iceland. METHODS: The study base was comprised of all 371 men born in 1924-1969 who were widowed in Iceland in 1999-2001 and 357 controls, married men, who were matched by age and residence.The widowers and controls were followed through the years 2002-2007 using information from Statistics Iceland. Mortality rates were compared between the groups and also with the general population. The mortality rate comparisons were: study group vs. control group, on the one hand, and study group vs. general population on the other. Causes of death were also compared between widowers and their wives. RESULTS: A statistically significant increase in mortality in the widowers' group, compared to controls, was observed.Lifestyle-related factors could not be excluded as contributing to cause of death in these cases. CONCLUSIONS: Being a widower was related to an increased risk of death for at least 9 years after the death of their wife. PMID- 22299755 TI - Trichophyton tonsurans induced recurrent onychomadesis in a very young infant. AB - Onychomadesis, or nail shedding, is rarely seen in children and can be due to stress, systemic illnesses, trauma, and drug therapy or may be idiopathic. Fungal infection of the nail is only rarely reported as a cause of onychomadesis. We present here a case of Trichophyton tonsurans-induced onychomycosis and resultant onychomadesis in a 9-month-old boy with onset of lesions at 2 weeks of life. PMID- 22299756 TI - Comparison of seven liver allocation models with respect to lives saved among patients on the liver transplant waiting list. AB - The patients with end-stage liver disease (ESLD) on the liver transplant waiting list are prioritized for transplant based on the model for end-stage liver disease (MELD) score. We developed and used an innovative approach to compare MELD to six proposed alternatives with respect to waiting list mortality. Our analysis was based on United Network for Organ Sharing data of patients with ESLD on the waiting list between January 2006 and June 2009. We compared six allocation models to MELD. Two models were based on reweighting the variables used by MELD: an "updated" MELD, and ReFit MELD. Four models also included serum sodium: MESO, MeldNa, UKELD, and ReFit MELDNa. We estimated that UKELD and the updated MELD would result in significantly fewer lives saved. There were no significant differences between the other models. Our new approach can supplement standard methods to provide insight into the relative performance of liver allocation models in reducing waiting list mortality. Our analysis suggests that UKELD and the updated MELD score would not be optimal for reducing waiting list mortality in the United States. PMID- 22299757 TI - Chronic kidney disease stressors influence choice of dialysis modality. AB - AIM: This article is a report of a study examining the relationships between chronic kidney disease stressors and coping strategies with dialysis modality. BACKGROUND: People with chronic kidney disease are given information to enable dialysis modality choice. This education increases awareness and may alleviate concerns and stress. Disease-related stressors and coping may affect dialysis selection. Understanding the influence of stress and coping on dialysis choices will assist in providing responsive programmes. Reducing stress and encouraging coping may increase home dialysis which, despite economic and patient benefits, remains underused. DESIGN: A prospective correlational design was used. METHODS: Information was obtained from the Chronic Kidney Disease Stress Inventory and the Jalowiec Coping Scale in 223 individuals not on dialysis between the years 2005-2007. Data were recorded with respect to modality at dialysis initiation (n = 76) from 2005-2010. The effects of stress, coping and patient parameters on modality selection were compared using bivariate and multivariate analyses. RESULTS: Individuals on home dialysis vs. in-centre haemodialysis reported significantly fewer pre-dialysis stressors. Coping was not associated with dialysis modality. Individuals on in-centre haemodialysis had a lower serum creatinine, less advanced kidney disease and weighed more than those who started on a home therapy. Physiological stressors were most common and are amenable to interventions. CONCLUSION: Pre-dialysis stress levels predicted dialysis modality. Interventional studies are recommended to address chronic kidney disease stressors with the outcome of improving home-dialysis usage. PMID- 22299758 TI - Using stable isotopes to differentiate trophic feeding channels within soil food webs. AB - The soil is probably the most diverse habitat there is, with organisms ranging in sizes from less than 1 MUm to several metres in length. However, it is increasingly evident that we know little about the interactions occurring between these organisms, the functions that they perform as individual species, or together within their different feeding guilds. These interactions between groups of organisms and physical and chemical processes shape the soil as a habitat and influence the nature of the soil food web with consequences for the above-ground vegetation and food web. Protists are known as one of the most abundant groups of bacterivores within the soil; however, they are also consumers of a number of other food sources. Even though they are responsible for a large proportion of the mineralisation of bacterial biomass and have a large impact on the C and N cycles within the soil they are regularly overlooked when investigating the complete soil food web. Recently, stable isotopes have been used to determine trophic interactions and here we describe how this technique has been used to highlight linkages between protists and the soil food web. PMID- 22299759 TI - Assessing stakeholder opinion on relations between cancer patient groups and pharmaceutical companies in Europe. AB - BACKGROUND: The relationship between the pharmaceutical industry and cancer patient groups has been the subject of much scrutiny and skepticism, and some high-profile negative media coverage has focused attention on some of the problematic aspects of the relationship. Both the pharmaceutical industry and cancer patient groups have made an effort in recent years to improve the transparency and openness of their relations, specifically with regard to the financial support offered by pharmaceutical companies to patient groups. OBJECTIVE: The objectives of this survey were to benchmark perceptions held by different stakeholder groups about current relationships between cancer patient groups and pharmaceutical companies in Europe, and to explore opinions about ways in which partnerships between patient groups and pharmaceutical companies could evolve to the benefit of cancer patients. METHODS: The survey was conducted using a structured questionnaire that contained a combination of matrix, scaled, and open-ended questions. The questionnaire was developed based on a literature search and the findings from ten in-depth interviews conducted with policy makers and advocates working at an EU level. Telephone interviews were carried out using a structured questionnaire with a convenience sample of 161 policy makers, cancer healthcare group representatives, and cancer patient group leaders from France, Germany, Hungary, Italy, Latvia, the Netherlands, Poland, Portugal, Romania, Spain, Sweden, and the UK. The interviews took place in the relevant language of the country. RESULTS: The current relationship between the pharmaceutical industry and cancer patient groups in Europe is generally viewed as positive, but it is also viewed as being unequal, not transparent enough, and not sufficiently patient-centric. There is broad agreement that cancer patient groups can help companies identify unmet needs and contribute to the development of innovative medicines; however, there is some concern about cancer patients' competence to take on this role. Also, pharmaceutical companies and patient groups have a common interest in working together on the development of non-promotional patient information and strategies to support medicines adherence. Respondents also indicated that the two sectors have a legitimate interest in ensuring that patients in need access appropriate treatments in a timely manner. Ongoing cooperation between health professionals, pharmaceutical companies, and cancer patient groups is also viewed as important. Efforts should continue to make relations between pharmaceutical companies and cancer patient groups as equal, open, and transparent as possible. CONCLUSION: Despite ongoing concerns about the openness and transparency of relations between pharmaceutical companies and patient groups, there is scope for these two sectors to work together on issues of common interest. PMID- 22299760 TI - Patients' expectation and satisfaction with removable dental prosthesis therapy and correlation with patients' evaluation of the dentists. AB - OBJECTIVE: Considering that patients' satisfaction is one of the most important goals in conducting removable dental prosthesis (RDP) therapy and the fact that there are many factors which influence this parameter, the present study aims to evaluate the expectation before and satisfaction after therapy with RDP in patients who seek such therapy. As a secondary objective, other variables that may be associated with patient satisfaction are also evaluated, such as gender, age, Kennedy's classification of the arch supporting the RDP, the number of RDP adjustments after delivery and patients' evaluation of the dentists' conduct. MATERIALS AND METHODS: A sample of 44 patients who received RDP therapy were assigned visual analog scale scores for their expectation before and satisfaction after therapy regarding chewing, aesthetics, comfort and phonetics. They also completed a questionnaire concerning the dentists' conduct. RESULTS: There was no statistically significant difference among scores concerning different genders, age, number of post-delivery settings and arch involved in the RDP. Regarding patients' evaluation of the dentists' conduct, there was a predominance of positive evaluations, but only different answers to the statement (i.e. 'The dentist I saw thoroughly explained the recommended treatment before it commenced') present statistically significant different scores for chewing (p = 0.040) and phonetics (p = 0.046). CONCLUSIONS: The average visual analog scale scores were high for both expectation prior to treatment and satisfaction after treatment; however, the scores for expectations were higher than those for satisfaction. PMID- 22299761 TI - A randomized, placebo-controlled study to assess the efficacy of lateral branch neurotomy for chronic sacroiliac joint pain. AB - OBJECTIVE: The objective of this study was to compare the efficacy of lateral branch neurotomy using cooled radiofrequency to a sham intervention for sacroiliac joint pain. DESIGN: Fifty-one subjects were randomized on a 2:1 basis to lateral branch neurotomy and sham groups, respectively. Follow-ups were conducted at 1, 3, 6, and 9 months. Subjects and coordinators were blinded to randomization until 3 months. Sham subjects were allowed to crossover to lateral branch neurotomy after 3 months. SUBJECTS: Subjects 18-88 years of age had chronic (>6 months) axial back pain and positive response to dual lateral branch blocks. INTERVENTIONS: Lateral branch neurotomy involved the use of cooled radiofrequency electrodes to ablate the S1-S3 lateral branches and the L5 dorsal ramus. The sham procedure was identical to the active treatment, except that radiofrequency energy was not delivered. OUTCOME MEASURES: The principal outcome measures were pain (numerical rating scale, SF-36BP), physical function (SF 36PF), disability (Oswestry disability index), quality of life (assessment of quality of life), and treatment success. RESULTS: Statistically significant changes in pain, physical function, disability, and quality of life were found at 3-month follow-up, with all changes favoring the lateral branch neurotomy group. At 3-month follow-up, 47% of treated patients and 12% of sham subjects achieved treatment success. At 6 and 9 months, respectively, 38% and 59% of treated subjects achieved treatment success. CONCLUSIONS: The treatment group showed significant improvements in pain, disability, physical function, and quality of life as compared with the sham group. The duration and magnitude of relief was consistent with previous studies, with current results showing benefits extending beyond 9 months. PMID- 22299762 TI - Novel FLG mutations associated with ichthyosis vulgaris in the Chinese population. AB - Loss-of-function mutations in the gene encoding filaggrin (FLG) can cause the semidominant keratinizing disorder ichthyosis vulgaris (OMIM 146700). To identify FLG mutations in three Chinese pedigrees with ichthyosis vulgaris, we sequenced the entire coding region of FLG in the proband of each pedigree. We found two novel FLG null mutations (c.477-478insA and c.6218-6219delAA) and a known mutation (c.3321delA). Both novel mutations were identified in the proband of pedigree 1; c.477-478insA was inherited from the proband's father, and the other was a de novo mutation. Neither of these two mutations was found in 200 unrelated controls. These findings extend the spectrum of functional FLG variants possibly causing ichthyosis vulgaris. Interestingly, the proband of pedigree 1 was compound heterozygous for these mutations, but had a mild phenotype, suggesting that an incomplete penetrance factor and perhaps other unknown factors may be involved in the pathogenesis of ichthyosis vulgaris. PMID- 22299763 TI - A comparison of two approaches to increasing access to care: expanding coverage versus increasing physician fees. AB - OBJECTIVE: To compare the effects of a coverage expansion versus a Medicaid physician fee increase on children's utilization of physician services. PRIMARY DATA SOURCE: National Health Interview Survey (1997-2009). STUDY DESIGN: We use the Children's Health Insurance Program, enacted in 1997, as a natural experiment, and we performed a panel data regression analysis using the state year as the unit of observation. Outcomes include physician visits per child per year and the following indicators of access to primary care: whether the child saw a physician, pediatrician, or visited an ER in the last year, and whether the parents reported experiencing a non-cost-related access problem. We analyzed these outcomes among all children, and separately among socioeconomic status (SES) quartiles defined based on family income and parents' education. PRINCIPAL FINDINGS: Children's Health Insurance Program had a major impact on the extent and nature of children's insurance coverage. However, it is not associated with any change in the aggregate quantity of physician services, and its associations with indicators of access are mixed. Increases in physician fees are associated with broad-based improvements in indicators of access. CONCLUSIONS: The findings suggest that (1) coverage expansions, even if they substantially reduce patient cost sharing, do not necessarily increase physician utilization, and (2) increasing the generosity of provider payments in public programs can improve access among low-SES children, and, through spillover effects, increase higher SES children as well. PMID- 22299764 TI - Prevalence rates of sexual coercion victimization and perpetration among Uganda adolescents. AB - Coercion is consistently reported as a risk factor for HIV in sub-Saharan Africa (SSA). Because of the gendered nature of previous research, however, little is known about male victims or female perpetrators. To address this gap, we report survey data from 354 sexually experienced secondary school students in Mbarara, Uganda. Findings suggest that females are more likely to report involvement in coercive sex compared to males (66% vs. 56%, respectively). Of those involved, females are most likely to report being a victim-only (40%) and males, perpetrator-victims (32%). Although involvement in violent and coercive sex is gendered, 47% of males report victim experiences and 25% of females report perpetration behavior. Furthermore, about one in ten female and male perpetrators reported using physical force or threats to compel sex. When all potentially influential factors were considered simultaneously, several characteristics seem to differentiate youth by their coercive sex (in) experience. For example, victims are more likely to have lower levels of social support from their families and feel that they have an above average or very strong chance of getting HIV compared to otherwise similar youth with no experience with coercive sex. Perpetrators are more likely to have had an HIV test but use condoms less than half the time or never compared to their otherwise similar, yet uninvolved peers. They also are significantly more likely to report dating violence perpetration. Perpetrator-victims share some similarities with other involved youth, as well as some differences. Findings underscore both the importance of asking all youth, irrespective of biological sex, perpetrator and victimization questions; and also the need for more work to be done to help youth plan for a healthy and wanted first sexual experience. PMID- 22299765 TI - Quality assessment of clinical practice guidelines for the prescription of antidepressant drugs during pregnancy. AB - Antidepressant use during the gestational period remains a controversial issue. The objective of this study was to appraise the quality of the available clinical practice guidelines (CPGs) that includes recommendations for antidepressant use during pregnancy. We systematically searched for documents published between January 2000 and September 2010 in MEDLINE / TRIP database and on clearing houses and main scientific societies' websites. Four appraisers evaluated each guideline using the Appraisal of Guidelines for Research and Evaluation tool (AGREE II). Intra-class correlation coefficients (ICC) with 95% confidence intervals (CI) were calculated as an overall indicator of agreement. Twelve CPGs were included from a total of 539 references. Only two guidelines were specifically addressed to pregnant women. The overall agreement among reviewers was high (ICC: 0.94, 95% CI: 0.86-0.98). The mean scores and standard deviation (SD) for each of the AGREE II domains were: scope and purpose: 84.4% (12); stakeholder involvement: 67.4% (29.8); rigor of development: 68.6% (19.8); clarity and presentation: 83.4% (17.4); applicability: 44% (37.3); and editorial independence: 62.1% (30.4). After standardizing the scores of the 12 guidelines, 5 were considered as being "recommended", 5 as "recommended with modifications, and 2 as "not recommended". Among the five recommended guidelines, two were specifically conceived to the gestational period. CPGs containing recommendations for antidepressant use during pregnancy were of moderate to high quality. Future guidelines should take into account the observed drawbacks in some domains, and specifically focus a more in depth approach of depression during pregnancy. PMID- 22299766 TI - Structure-activity relationships and drug allergy. AB - Structure-activity relationships (SARs) refer to the relation between chemical structure and pharmacologic activity for a series of compounds. Since the pioneering work of Crum-Brown and Fraser in 1868, they have been increasingly used in the pharmaceutical, chemical and cosmetic industries, especially for drug and chemical design purposes. Structure-activity relationships may be based on various techniques, ranging from considerations of similarity or diversity of molecules to mathematical relationships linking chemical structures to measured activities, the latter being referred to as quantitative SAR or QSAR. This review aims at briefly reviewing the history of SARs and highlighting their interest in delayed and immediate drug allergy using selected examples from the literature. Studies of SAR are commonly conducted in the area of contact dermatitis, a delayed hypersensitivity reaction, to determine the allergenic potential of a given compound without animal testing. In immediate, immunoglobulin E-mediated drug hypersensitivity, this kind of approach remains rather confidential. It has been mainly applied to neuromuscular blocking drugs (muscle relaxants) and betalactam antibiotics (penicillins, cephalosporins). This review shows that SARs can prove useful to (i) predict the allergenic potential of a chemical or a drug, (ii) help identify putative antigenic determinants for each patient or small group of patients sharing the same cross-reactivity pattern, and (iii) predict the likelihood of adverse reactions to related molecules and select safe alternatives. PMID- 22299767 TI - Confounding issues in estimation of patient-specific pharmacokinetic parameters and dosage individualization of aminoglycosides. AB - Aminoglycoside antibiotics are usually administered by multiple short intravenous infusions at fixed intervals. Today, equations reported 35 years ago by Sawchuk and Zaske are still the cornerstone of methods used for determination of patient specific pharmacokinetic parameters of aminoglycosides and individualization of drug dosage regimens in many clinical settings. Additionally, these methods are included in many clinical pharmacology curricula in pharmacy and other related fields. However, there are a few issues with regard to the application and/or modification of this method in clinical settings, which may result in some confusion among novice clinicians. For example, serum samples collected from different intervals at steady state, instead of samples obtained during the same interval, require special manipulation of sampling time before they can be used for estimation of pharmacokinetic parameters. Furthermore, there are various ways that the original equations are modified or simplified, which can result in some degree of error in the estimates of pharmacokinetic parameters and ensuing dosage regimen calculations. Simulation data presented here indicate that in some cases, these errors may be substantial, depending on the length of short infusion, half life of the drug, and the dosage interval. For instance, using equations developed for intravenous bolus mode of administration, ignoring the short infusion, may result in >= 25% error for a typical patient and dosing scenario. Although experts may use modified equations, understanding their error ramifications, these modifications may be confusing to the novice clinician. Therefore, it is recommended that exact equations developed specifically for multiple intravenous infusions be used without any modification, particularly in settings where clinicians are being trained. PMID- 22299768 TI - Nifedipine blocks ondansetron electrophysiological effects in rabbit purkinje fibers and decreases early after depolarization incidence. AB - We hypothesized that a high concentration of nifedipine (1 MUM), known to inhibit at least 75%of L-type Ca++ current, might counteract proarrhythmic dose-dependent effects of ondansetron (0.1 to 10 MUM) in rabbit Purkinje fibers. Ondansetron is a 5-HT3 receptor antagonist commonly prescribed to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy, and surgery but may increase the risk of developing prolongation of the QT interval of the electrocardiogram, which can lead to an abnormal and potentially fatal heart rhythm and recently raised FDA concerns and warnings. Neostigmine, a quaternary nitrogen agent that was also used clinically concomitant to antiemetics after anesthesia was further investigated dose-dependently (0.1 to 10 MUM) and at fixed concentration (10 MUM) with 0.1 to 10 MUM ondansetron. The protocol included use-dependent (1 to 0.33 Hz) studies. APD durations, triangulation and early after depolarization (EAD) incidence were assessed. Ondansetron increased APD50, APD70 and APD90 (0.01 > p < 0.05) dose-dependently. APD90 averaged 102?1%of baseline to 302?49%dose dependently (p < 0.001) and, at the highest dose, increased to 511?73%reverse use dependently (p < 0.001). EAD were seen at top concentrations (33%) which were increased at lower rates (50%). Neostigmine induced reverse use-dependent APD changes (p < 0.05) but no EAD. In preparations treated by nifedipine and ondansetron, APD90 changes averaged 101?2%of baseline to 151?8%dose-dependently (p < 0.01) and to 193?13%reverse use-dependently (p < 0.05) and no EAD were seen. Thus nifedipine significantly shortened ondansetron-induced APD changes (p < 0.01), whereas neostigmine only slightly shortened ondansetron-induced APD changes (p < 0.05). There was a tendency for increased incidence of EAD (p < 0.06) in the ondansetron and neostigmine group vs. neostigmine alone. It is concluded that inhibition of L-type Ca++ current by high concentration nifedipine may counteract the ondansetron effects on APD changes. PMID- 22299769 TI - Antipsychotic medication adherence and satisfaction among Palestinian people with schizophrenia. AB - BACKGROUND: In Arab and Muslim-dominated countries, spirituality and religiosity shape the belief and practices toward chronic illnesses. No previous studies were published to assess adherence to and satisfaction with antipsychotic medications in persons with schizophrenia in the Arab world. OBJECTIVE: To assess medication adherence and treatment satisfaction with antipsychotics in a sample of Palestinian people with schizophrenia. METHODOLOGY: Medication adherence was assessed using the 8-item Morisky Medication Adherence Scale (MMAS-8). Treatment satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4). Psychiatric symptoms were assessed using the expanded Brief Psychiatric Rating Scale (BPRS-E). Data were entered and statistically analyzed using SPSS 16 for windows. RESULTS: A convenience sample of 131 persons with schizophrenia was studied. Based on MMAS-8, 44 persons (33.6%) had a low rate, 58 (44.3%) had a medium rate and 29 (22.1%) had a high rate of adherence. Age was significantly correlated (P=0.028) with adherence score. However, variables like use of monotherapy or atypical or depot antipsychotics were not significantly associated with higher adherence. The means of satisfaction with regard to effectiveness, side effects, convenience and global satisfaction were 72.6 +/- 20.5, 67.9 +/- 31.47, 63.2 +/- 14.3 and 63.1 +/- 18.8 respectively. There was a significant difference in the means of effectiveness (P < 0.01), convenience (P < 0.01), global satisfaction (P < 0.01), but not side effects domains (P=0.1) among persons with different levels of adherence. Furthermore, there was a significant difference in the means of positive symptom score (P < 0.01), manic (P < 0.01) and depression (P < 0.01) but not negative symptom score (P=0.4) among persons with different levels of adherence. CONCLUSIONS: Medication nonadherence was common and was associated with low treatment satisfaction scores and poor psychiatric scores. Medication related factors had insignificant effects on adherence scores. PMID- 22299771 TI - Clinical pharmacology of current and future drugs for the acute treatment of migraine: a review and an update. AB - Migraine is a common disorder with a female prevalence of 17% and a male prevalence of 9%. Migraine is most often disabling and the patients need treatment of the attacks. The introduction of triptans has been a revolution for many migraine patients but only a minority of patients use these specific drugs. The pharmacokinetics and efficacy and tolerability of triptans are reviewed. The triptans can most likely with advantage be combined with NSAIDs and prokinetic drugs. Among future drugs, CGRP receptor antagonists are the most promising. These drugs have shown excellent tolerability with no more adverse events than placebo, but only one quarter of migraine patients have been pain-free after 2 hours in phase III studies. The development of current CGRP antagonists has been stopped. PMID- 22299770 TI - Systematic review on infusion reactions associated with chemotherapies and monoclonal antibodies for metastatic colorectal cancer. AB - OBJECTIVE: The objective of this systematic review is to summarize the literature to date on the rates of infusion reactions (IR) associated with chemotherapies and monoclonal antibody (mAb) drug therapies used for the treatment of metastatic colorectal cancer (mCRC) and the associated clinical and economic impact. METHODS: This study searched Medline, Medline (R) In-Process, Embase and Cochrane Library databases for studies on IRs associated with chemotherapy and mAbs in mCRC patients from 2000-2011. RESULTS: For chemotherapy, the incidence of IRs ranged from 0-71% for all grades and 0-15% for grade 3-4. Rates of all grade IRs associated with cetuximab ranged from 7.6-33% and grade 3-4 IR rates were 0-22%. Rates of all grade IRs associated with panitumumab ranged from 0-4% and rates of grade 3-4 IRs ranged from 0-1%. The overall rate of IRs associated with bevacizumab ranged from 1.6-11%, with a rate of 0-4% for grade 3-4 IRs. A range of 50-100% of patients with grade 3-4 IRs terminated chemotherapy, and 34-100% of cetuximab patients with grade 3-4 IRs discontinued cetuximab therapy. No data were reported for bevacizumab or panitumumab. Only one study evaluated the economic impact of IRs. The study compared cetuximab administrations without an IR to those with an IR requiring resource utilization and found that mean costs were $9308 and $1725 higher for those with an IR requiring an emergency room visit or hospitalization and for those with an IR requiring outpatient treatment, respectively. CONCLUSIONS: The incidence of IRs varies among different mAbs; and IRs may cause treatment disruption and require costly medical interventions. PMID- 22299773 TI - Hospital management and outcomes of stroke in Indigenous Australians: evidence from the 2009 Acute Care National Stroke Audit. AB - BACKGROUND: Indigenous Australians have greater stroke mortality rates than non Indigenous people (97% Indigenous Australians are aged <65 years). Quality of care in hospital is an important factor for avoiding death and disability. No national review of acute stroke care for Indigenous Australians is available. AIMS: We aimed to compare adherence with clinical processes and outcomes among Indigenous and non-Indigenous patients with acute stroke admitted to hospital. METHODS: Hospitals participating in the National Stroke Audit of acute services in 2009 that provided data for at least one Indigenous patient were included (n = 33, 37%). Differences in death/dependency (modified Rankin Score 3-6) at discharge were determined using two-level multivariate analysis adjusting for hospital site and patient variables. A matched subgroup analysis in those aged 18 to 64 years was also undertaken. RESULTS: Among 1162 eligible patients (60% male; 18-64 years n = 305), 7% were Indigenous (18-64 years: 18%). Indigenous patients had a greater prevalence of stroke risk factors, e.g. diabetes, more had intracerebral hemorrhages (25% vs. 16% non-Indigenous, P = 0.05), and were less likely be treated in a stroke unit and receive timely allied health assessments than non-Indigenous patients. Indigenous patients aged 18-64 years had a threefold odds of dying or being dependent at discharge (Adjusted odds ratio = 3.09, 95% confidence interval = 1.07-8.95). CONCLUSIONS: Australian Indigenous patients with stroke received a reduced quality of care in hospitals and experienced worse outcomes than non-Indigenous patients. Indigenous patients require the provision of evidence-based care to increase their opportunities for optimal health outcomes following stroke. Further research to explain the differences is needed. PMID- 22299774 TI - Reducing the burden of morbidity and medical utilization of older patients by outpatient geriatric services: implications to primary health-care settings. AB - AIM: That geriatric evaluation and management (GEM) is associated with better quality of care for elderly patients has been reported by previous studies, but evidence supporting that GEM can reduce the burden of morbidity (BOM) was lacking. The aim of this study was to evaluate the benefits of outpatient GEM on reducing BOM and medical utilization in Taiwan. METHODS: Data of this retrospective case-control study were obtained from the 2004-2006 Taiwan National Health Insurance Research Database (NHIRD). Patients who attended the outpatient GEM program for over 6 months in a tertiary medical center in 2005 were enrolled as the case group, and a 1:5 age and gender-matched control group was formed by randomly-selected patients from the same medical center for comparisons. BOM was obtained by applying the Adjusted Clinical Group (ACG) program, and medical utilization variables were totalled for each patient from the NHIRD. Patients were further reassigned to two morbidity categories, the low (resource utilization bands <= 3) and high (resource utilization bands > 3) morbidity category, according to their degree of morbidity before statistical analyses. RESULTS: Data of 4254 elderly patients (709 cases, 3545 controls) were included in the study. BOM and medical utilization were increased in both groups in both morbidity categories during the study period. However, the growth of BOM, total medical expenditure, number of emergency department visit, and days and expenditure of hospitalization were significantly reduced in the case than the control group in the low morbidity category, not the high morbidity category. CONCLUSION: Outpatient GEM could effectively reduce growth of BOM and medical utilization for relatively healthy elderly patients in Taiwan where elderly patients have relatively free access to general and specialty care. The results of this study implied the potential benefits of systematically implementing GEM in primary health-care settings to improve the quality of care and slow down the growth of BOM for elderly patients. PMID- 22299775 TI - Imatinib resistant BCR-ABL1 mutations at relapse in children with Ph+ ALL: a Children's Oncology Group (COG) study. PMID- 22299776 TI - The effects of social connections on self-rated physical and mental health among internal migrant and local adolescents in Shanghai, China. AB - BACKGROUND: China is in the midst of history's largest flow of rural-urban migration in the world; a flow that includes growing numbers of children and adolescents. Their health status is an important public health issue. This study compares self-rated physical and mental health of migrant and local adolescents in China, and examines to what extent layered social connections account for health outcomes. METHODS: In 2010, we conducted a cross-sectional study among middle school students in Pudong New Area, Shanghai. Information about health status, social connections, and demographic factors were collected using a questionnaire survey. After controlling for sociodemographic factors, we used the t-test, Chi-square analysis, and a series of regression models to compare differences in health outcomes and explore the effects of social connections. RESULTS: Migrant adolescents reported significantly higher rates of good physical health. However, they also had significantly fewer social connections, lower self esteem, and higher levels of depression than their native peers. Family cohesion was associated with depressive symptoms and low self-esteem among all adolescents; peer association and social cohesion played major roles in migrants' well-being. Gender, age, and socioeconomic (SES) factors also affected adolescents' self-rated physical and mental health. CONCLUSIONS: Self-rated data suggest that migrant adolescents enjoy a physical health advantage and a mental health disadvantage. Layered social connections, such as peer association and social cohesion, may be particularly important for migrants. A public health effort is required to improve the health status of migrant youth. PMID- 22299777 TI - Effects of (-)-epigallocatechin gallate on the motility and penetrability of frozen-thawed boar spermatozoa incubated in the fertilization medium. AB - Epigallocatechin gallate (EGCG) is the major polyphenol in green tea (Camellia sinensis) and is known for its antioxidant effects. The objective of the present study was to examine the effects of EGCG during in vitro fertilization (IVF) on the sperm quality and penetrability into oocytes. In the first experiment, the effects of concentration and incubation period of EGCG on the motility and penetrability of spermatozoa were examined. When frozen-thawed spermatozoa were incubated in IVF medium supplemented with 0 (control), 1, 50 and 100 MUm EGCG for 1, 3 and 5 h, supplementation with 50 and 100 MUm EGCG improved motility of the spermatozoa (p < 0.05), but not viability, as compared with the control group. When frozen-thawed spermatozoa were co-incubated with in vitro-matured (IVM) oocytes in IVF medium supplemented with 50 and 100 MUm EGCG for 5 h, supplementation of EGCG had positive effects on sperm penetration rates. In the second experiment, the effects of supplementation of EGCG in IVF medium on penetrability of sperm from different boars and development of fertilized oocytes were evaluated. When frozen-thawed spermatozoa from six boars were co-incubated with IVM oocytes in IVF medium supplemented with 50 MUm EGCG, the effect of EGCG on sperm penetration and development of oocytes after fertilization was found to vary with individual boar. Our results indicate that motility and penetrability of boar spermatozoa are improved by co-incubation with 50 MUm EGCG, but the effects vary with individual boars. PMID- 22299778 TI - Impact of sirolimus duration on hepatitis C related fibrosis progression in liver transplant recipients. PMID- 22299779 TI - Binding of DDT to dissolved humic materials. PMID- 22299780 TI - Organic carbon removal by advanced waste water treatment processes. PMID- 22299781 TI - Sludge disposal in Southern California basins. PMID- 22299782 TI - Initial sedimentation of waste particulates discharged from ocean outfalls. PMID- 22299783 TI - Characterization of fluorocarbon-film bags as smog chambers. PMID- 22299784 TI - Acid precipitation and lake susceptibility in the central Washington Cascades [USA]. PMID- 22299785 TI - Mineral matter and trace-element vaporization in a laboratory-pulverized coal combustion system. PMID- 22299786 TI - Analysis for organic vapor emissions near industrial and chemical waste disposal sites. PMID- 22299787 TI - Factors affecting the amperometric determination of trace quantities of total residual chlorine in sea water. PMID- 22299788 TI - Chlorination of estuarine water: the occurrence and magnitude of carbon oxidation and its impact on trace-metal transport. PMID- 22299790 TI - Persistent organic chemicals in sewage effluents. 2. Quantitative determinations of nonylphenols and nonylphenol ethoxylates by glass capillary gas chromatography. PMID- 22299789 TI - Synthesis and analysis of crystalline silica. PMID- 22299791 TI - Determination of naphtho[2,1,8-qra]naphthacene in soots. PMID- 22299792 TI - Removal and recovery of arsenous oxide from flue gases. A pilot study of the activated carbon process. PMID- 22299793 TI - Development and evaluation of sunlight actinometers. PMID- 22299794 TI - Entrapment of zinc and other trace elements in a rapidly flushed industrializaed harbor. PMID- 22299795 TI - Notes. Mutagenicity of SRC-II coal liquefaction wastewater treatment residues. PMID- 22299796 TI - Correction. Toxaphene residues in fish: identification, quantification, and confirmation at part per billion levels. PMID- 22299798 TI - Systemic contact dermatitis--kids and ketchup. AB - Systemic manifestations of allergic contact dermatitis due to consumption of foods containing balsam of Peru (Myroxylon pereirae)-associated chemicals have recently been reported in children. We present seven children with widespread, recalcitrant dermatitis who experienced 60-80% clearance after initiating a diet low in balsam of Peru, specifically the tomato product ketchup. Furthermore, because we have observed a high prevalence of ketchup in our pediatric patients' diets, we recommend consideration of moderate consumption of this product in patients with recalcitrant widespread dermatitis. PMID- 22299799 TI - Publication ethics: its importance to readers, authors, and the profession. PMID- 22299800 TI - Comment on "Ready or not-here we go into our future". PMID- 22299801 TI - Motivational interviewing with adolescents: an advanced practice nursing intervention for psychiatric settings. AB - TOPIC: The article focuses on the use of motivational interviewing (MI) as an intervention with adolescent patients in mental health treatment settings. PURPOSE: The aim of the study is to review MI theory and principles, and inform advanced practice nurses about the suitability of this intervention for adolescents in psychiatric care settings. For this population, MI may be effective in encouraging behavioral change consistent with a harm reduction approach. SOURCES USED: Published literature on the topic, including randomized controlled trials, was used in this study. CONCLUSIONS: Nurse practitioners in psychiatry are especially well suited to engage their adolescent patients in MI based on their role as patient advocates and the developmental framework within which they practice. Further studies are needed to evaluate the efficacy of this approach with the adolescent psychiatric population. PMID- 22299802 TI - Externalizing metaphors: anxiety and high-functioning autism. AB - TOPIC: The intent of this article is to explore the efficacy of both the literal and concrete externalization aspects within narrative therapy, and the implementation of interactive metaphors as a combined psychotherapeutic approach for decreasing anxiety with people who present with high-functioning autism. PURPOSE: The purpose of this exploratory article is to propose the use of externalizing metaphors as a treatment modality as a potentially useful way to engage clients. Specifically, a three-step process of change is described, which allows for concretizing affective states and experiences, and makes use of visual strengths of people presenting with an autism spectrum disorder. SOURCE: A selective review was conducted of significant works regarding the process of change in narrative therapy, with particular emphasis on metaphors. Works were selected based on their relevance to the current paper and included both published works (searched via Psyc-INFO) and materials from narrative training sessions. CONCLUSIONS: Further research is needed to address the testable hypotheses resulting from the current model. This line of research would not only establish best practices in a population for which there is no broadly accepted treatment paradigm, but would also contribute to the larger fields of abnormal psychology, emotion regulation, and cognitive psychology by further elucidating the complex ways these systems interact. PMID- 22299803 TI - Children with behavioral/mental health disorders and school mental health nurses in Australia. AB - TOPIC: This review of the literature addresses Australian school mental health nursing is an emergent field of practice. PURPOSE: Children with behavioral/mental health disorders present challenges to schools, teachers, and their families. They can be disruptive in class, inappropriate with their peers, and perform poorly academically. Often this group of children do not respond to the school's usual strategies to support appropriate behavior. When children with behavioral/mental health disorders do not receive specialized support based on their problems and needs, their problems can escalate over time and in adolescence their behavior may become more challenging, with increased aggression, substance use, contact with the criminal justice system, and school failure with or without dropout. CONCLUSION: Mental health nurses, working as case managers, could be effective in the support of children with behavioral/mental health disorders in schools. Mental health nurses, because of their professional education and clinical practice, work not only with the individual child but also with family members. They are well prepared to case manage in schools and support individual teachers and health and welfare services in their management of their clients with behavioral/mental health disorders. PMID- 22299804 TI - The impact of childhood sexual abuse on psychological distress among women in New Zealand. AB - PROBLEMS: In order to better understand the long-term impact of child sex abuse, this study examined the association between women's experience of abuse, health symptoms, and psychological distress in adulthood. There is limited information about child abuse outside the United States. METHODS: Nine hundred sixty-one women participated in a structured interview. RESULTS: Participants who had experienced abuse (13%) were significantly more vulnerable to psychological distress in adulthood if they were younger, less satisfied with their standard of living, and resided in urban areas. CONCLUSION: Dissemination and evaluation of therapies for the treatment of sex abuse in the New Zealand context is warranted. PMID- 22299805 TI - Contingency management in community programs treating adolescent substance abuse: a feasibility study. AB - PROBLEM: Adolescent substance abuse remains a public health problem, and more effective treatment approaches are needed. PURPOSE: The study aims to determine the feasibility and preliminary effectiveness of implementing a cost-effective contingency management (CM) intervention in community substance abuse treatment for adolescents with marijuana use disorders. METHODS: Thirty-one adolescents with primary marijuana use disorder enrolled in a community treatment were randomized into either a prize-based CM intervention contingent when submitting negative urine drug screens (UDS) or a noncontingent control group. FINDINGS: There were no significant group differences in percent negative UDS, sustained negative UDS, or retention in treatment. CONCLUSIONS: CM was difficult to integrate into community treatment programs and did not seem to be an effective adjunct to standard community substance abuse treatment for adolescents with marijuana use disorders. Modifying the CM procedure for adolescents, changing staff attitudes toward CM, and/or combining CM with other evidence-based psychosocial treatment may improve outcomes. PMID- 22299806 TI - Biopsychosocial model of hypersexuality in adolescent girls with bipolar disorder: strategies for intervention. AB - TOPIC: Engagement in high-risk behaviors, impaired judgment, and hypersexuality present unique health challenges to adolescent girls with bipolar disorder (BD). Behavioral management of sexuality does not routinely fall under the purview of psychiatric care, but requires preventive measures. PURPOSE: This paper presents a biopsychosocial model of hypersexuality in girls with BD, describes factors that lead to high-risk sexual behaviors, and provides a framework for cognitive behavioral intervention. SOURCES USED: The study used a review of empirically based clinical and research literature. CONCLUSIONS: Sexual health education, improved treatment adherence, symptom monitoring, interpersonal skills training, parental involvement, and clinician education can improve hypersexual behavior in girls with BD. PMID- 22299807 TI - Efforts to meet the mental health needs of children and adolescents. PMID- 22299808 TI - Managing the metabolic side effects of atypical antipsychotics. PMID- 22299809 TI - Embryonic and fetal development in - pigmy rice rat - Oligoryzomys sp. (Rodentia, Sigmodontinae) and its significance for being a new experimental model. AB - Oligoryzomys (Cricetidae, Sigmodontinae) is a common rodent genus from South America that includes a couple of very similar species. Related species have been used as experimental model for understanding several diseases for which these species are reservoirs. In order to provide a better understanding of the embryological aspects of this group, herein we showed data on the embryonic and fetal development in Oligoryzomys sp. Eight specimens of different stages of gestation were obtained from the Collection of the Zoology Museum of University of Sao Paulo, Brazil. Gestational ages were estimated by crown-rump-length according to Evans and Sack (1973). To address our analysis after examining the gross morphology, tissues from several organs were processed for light and scanning electron microscopy. Morphological data on the systems (nervous system, cardiorespiratory system, intestinal tract and urogenital system) were described in detail. Finally, the findings were compared with what is known about embryological aspects in other rodent species in order to establish similarities and differences during the organogenesis in different species. PMID- 22299810 TI - Cerebral blood flow dynamics during pain processing investigated by functional transcranial Doppler sonography. AB - OBJECTIVE: Functional transcranial Doppler sonography (fTCD) enables reliable quantification of cerebral blood flow modulation during neural activation processes. Its high-time resolution, relatively simple technical arrangement, and low costs could make fTCD a useful tool in the investigation of brain activity underlying pain experience in fundamental and clinical research. The present pilot study explored the suitability of this technique to investigate cerebral hemodynamics during the processing of experimental heat pain. DESIGN: In 46 healthy subjects, blood flow velocities in the anterior cerebral arteries (ACA) and middle cerebral arteries (MCA) of both hemispheres were recorded, while heat stimuli of 45 and 47 degrees C were applied to their left forearms (stimulus duration 20 seconds). Subjective sensory and affective pain intensities were assessed using visual analog scales. RESULTS: A biphasic right dominant blood flow increase arose in the ACA and MCA with maxima around 5 and 15 seconds after stimulus onset. The response was stronger under stimulation with 47 degrees C with respect to 45 degrees C, and the magnitude of the late response component correlated positively with sensory and affective pain intensity under the 45 degrees C condition. CONCLUSIONS: The findings suggest that fTCD measurements prove sensitive both to different levels of physical intensity of painful stimuli and to interindividual differences in nociceptive responding. fTCD may be a valuable tool in clinical pain research, for instance, when it comes to quantifying the temporal dynamics of exaggerated nociceptive responses in chronic pain, or evaluating treatment effects on nociceptive processing. PMID- 22299811 TI - Influence of cement thickness on the bond strength of tooth-colored posts to root dentin after thermal cycling. AB - OBJECTIVE: The purpose of this study was to evaluate the effect of different resin cement thickness on the push-out bond strength of different posts (CAD/CAM zirconia post (ZR post)) and an individually formed glass fiber reinforced composite post (IPN post) prior to and after thermal cycling (TC). METHODS: Post spaces with a height of 9 mm and a diameter of 1.5 mm were drilled in 80 mandibular premolar teeth. Two groups (n = 40) were formed according to the posts used (IPN posts or ZR posts). Then the specimens were randomly assigned into two sub-groups according to the post diameter: (1) 1.5 mm in diameter and (2) 1.2 mm in diameter (n = 20/per group). All posts were luted with a self-adhesive luting agent according to the manufacturer's instructions by using endo tips. Half of the samples (n = 10) were submitted to thermal cycling (5000 cycles, 5-55 degrees C). Thereafter, four 2-mm thick horizontal sections were obtained and subjected to push-out test. Failure modes were assessed quantitatively and morphologically. The data were statistically analyzed with a three-way analysis of variance (ANOVA) (p < 0.05). Statistical differences in failure modes were investigated by chi-square tests at a significance level of p < 0.05. RESULT: Push-out bond strengths were significantly influenced both by the post diameter and thermal cycling. Larger (1.5 mm) diameter post results were statistically higher than 1.2 mm results (p < 0.05). Moreover, TC significantly increased the bond strength results (p < 0.05). There was no significant difference between ZR and IPN posts (p = 0.219). CONCLUSION: The bond strengths of ZR and IPN posts were significantly decreased when the resin cement layer was thick. In addition, thermal cycling drastically influenced bond strengths of the tested post materials. CLINICAL SIGNIFICANCE: The fit between tooth-colored endodontic posts and post spaces should be as tight as possible. PMID- 22299813 TI - Proactive aging: a longitudinal study of stress, resources, agency, and well being in late life. AB - OBJECTIVES: Using the Proactivity Model of Successful Aging, we examined how internal and external resources contribute to the maintenance of psychological well-being and social activities among older adults who experience normative stressors of aging. Outcome variables in this study are collectively referred to as quality of life (QOL). We also examined the mediating role of proactive adaptations between internal and external resources and QOL indicators. METHOD: Based on five annual interviews of a sample of 1000 community-dwelling older adults in Florida (effective N = 561), we tested the lagged effects of stressors on two indicators of QOL, four years later. In the full longitudinal model, using structural equations, we estimated the direct effects of internal and external resources on QOL, along with indirect effects through proactive adaptations. RESULTS: Stressors negatively influenced QOL four years later. Internal and external resources led to better QOL four years later, both directly and indirectly through proactive adaptations of marshaling support and planning for the future. CONCLUSION: These findings lend support to the Proactivity Model of Successful Aging by documenting the value of proactive adaptations (i.e., exercise, planning ahead, and marshaling support) as proximate influences on QOL outcomes (i.e., depressive symptomatology and social activities). Findings suggest that older adults can maintain successful aging even in the face of health-related and social stressors by invoking accumulated resources to deal actively with the challenges of aging. PMID- 22299815 TI - Editorial: can we dissect the interplay of genes and environment across development? PMID- 22299812 TI - Circadian disruption and remedial interventions: effects and interventions for jet lag for athletic peak performance. AB - Jet lag has potentially serious deleterious effects on performance in athletes following transmeridian travel, where time zones are crossed eastwards or westwards; as such, travel causes specific effects related to desynchronization of the athlete's internal body clock or circadian clock. Athletes are particularly sensitive to the effects of jet lag, as many intrinsic aspects of sporting performance show a circadian rhythm, and optimum competitive results require all aspects of the athlete's mind and body to be working in tandem at their peak efficiency. International competition often requires transmeridian travel, and competition timings cannot be adjusted to suit individual athletes. It is therefore in the interest of the individual athlete and team to understand the effects of jet lag and the potential adaptation strategies that can be adopted. In this review, we describe the underlying genetic and physiological mechanisms controlling the circadian clock and its inherent ability to adapt to external conditions on a daily basis. We then examine the fundamentals of the various adaptation stimuli, such as light, chronobiotics (e.g. melatonin), exercise, and diet and meal timing, with particular emphasis on their suitability as strategies for competing athletes on the international circuit. These stimuli can be artificially manipulated to produce phase shifts in the circadian rhythm to promote adaptation in the optimum direction, but care must be taken to apply them at the correct time and dose, as the effects produced on the circadian rhythm follow a phase-response curve, with pronounced shifts in direction at different times. Light is the strongest realigning stimulus and careful timing of light exposure and avoidance can promote adjustment. Chronobiotics such as melatonin can also be used to realign the circadian clock but, as well as timing and dosage issues, there are also concerns as to its legal status in different countries and with the World Anti-Doping Agency. Experimental data concerning the effects of food intake and exercise timing on jet lag is limited to date in humans, and more research is required before firm guidelines can be stated. All these stimuli can also be used in pre-flight adaptation strategies to promote adjustment in the required direction, and implementation of these is described. In addition, the effects of individual variability at the behavioural and genetic levels are also discussed, along with the current limitations in assessment of these factors, and we then put forward three case studies, as examples of practical applications of these strategies, focusing on adaptations to travel involving competition in the Rugby Sevens World Cup and the 2016 Summer Olympics in Rio de Janeiro, Brazil. Finally, we provide a list of practice points for optimal adaptation of athletes to jet lag. PMID- 22299816 TI - 'Once seen, never forgotten'. PMID- 22299817 TI - Safety of deferasirox in sickle cell disease patients with co-existing liver impairment. PMID- 22299818 TI - Transcranial laser therapy for acute ischemic stroke: a pooled analysis of NEST-1 and NEST-2. AB - BACKGROUND: NeuroThera Effectiveness and Safety Trials (NEST) 1 and 2 have demonstrated safety of transcranial laser therapy (TLT) for human treatment in acute ischemic stroke. NEST 1 study suggested efficacy of TLT but the following NEST 2, despite strong signals, missed reaching significance on its primary efficacy endpoint. In order to assess efficacy in a larger cohort, a pooled analysis was therefore performed. METHODS: The two studies were first compared for heterogeneity, and then a pooled analysis was performed to assess overall safety and efficacy, and examined particular subgroups. The primary endpoint for the pooled analysis was dichotomized modified Rankin scale (mRS) 0-2 at 90 days. RESULTS: Efficacy analysis for the intention-to-treat population was based on a total of 778 patients. Baseline characteristics and prognostic factors were balanced between the two groups. The TLT group (n = 410) success rate measured by the dichotomized 90-day mRS was significantly higher compared with the sham group (n = 368) (P = 0.003, OR: 1.67, 95% CI: 1.19-2.35). The distribution of scores on the 90-day mRS was significantly different in TLT compared with sham (P = 0.0005 Cochran-Mantel-Haenszel). Subgroup analysis identified moderate strokes as a predictor of better treatment response. CONCLUSIONS: This pooled analysis support the likelihood that transcranial laser therapy is effective for the treatment of acute ischemic stroke when initiated within 24 h of stroke onset. If ultimately confirmed, transcranial laser therapy will change management and improve outcomes of far more patients with acute ischemic stroke. PMID- 22299819 TI - Perceived age of facial features is a significant diagnosis criterion for age related carotid atherosclerosis in Japanese subjects: J-SHIPP study. AB - AIM: Vascular aging is known to be a major determinant of life expectancy. Recently, perceived age was reported to be a better predictor for mortality than chronological age. Based on these findings, we investigated whether or not perceived age was related to atherosclerosis in a general population. METHODS: The participants were 273 individuals aged >= 50 years who participated in the Skin-doc in Anti-Aging Doc program. Facial photos were taken under a shadowless lamp from three directions (antero-posterior, and 60 degrees right and left oblique projection) using a high-resolution digital camera. Perceived age was assessed either by 19 professional nurses in the geriatric ward or using facial identification program software. Carotid intima-media thickness (IMT), radial augmentation index (AI) and brachial-ankle pulse wave velocity (baPWV) were measured as indices for atherosclerosis. RESULTS: The perceived age difference (expressed as the difference between perceived age and chronological age), when estimated either by nurses or software, was significantly and negatively associated with chronological age. Subjects who were evaluated by nurses to be younger than their chronological age had significantly lower carotid IMT after adjustment for chronological age. Conversely, carotid IMT was an independent and negative determinant of looking young, as perceived by nurses. Similar observations were also made between perceived age using facial identification software and carotid IMT. Radial AI and baPWV were not associated with perceived age. CONCLUSION: These findings show that carotid atherosclerosis is related to perceived age. This association might underlie previous findings showing that perceived age predicts life expectancy. PMID- 22299820 TI - An indirect comparison of everolimus versus sorafenib in metastatic renal cell carcinoma - a flawed analysis? PMID- 22299821 TI - Modification of crystallization behavior in drug/polyethylene glycol solid dispersions. AB - The crystallization kinetics of various active pharmaceutical ingredient/polyethylene glycol (API/PEG) solid dispersions has been investigated using wide-angle X-ray diffraction (XRD) and Raman spectroscopy. APIs with different physicochemical properties and crystallization tendency were employed to form solid dispersions with PEG. The crystallization rate of benzocaine (BZC) in BZC/PEG (20/80 wt %) solid dispersions was decreased substantially in comparison to that of the pure API, while the PEG matrix did not affect the crystallization behavior of haloperidol (HLP). The induction time for crystallization of ibuprofen (IBP) and fenofibrate (FNB) in a PEG matrix was decreased relative to the induction times for pure IBP and FNB. For the latter systems, it appears that crystalline PEG acted as a favorable heterogeneous nucleation site. The crystallization behavior of PEG in the API/PEG systems was also affected to different extents, depending on the API studied. These results suggest that PEG can delay, promote or have no influence on the crystallization kinetics of different APIs, and that any effects on crystallization behavior should be investigated in order to be able to produce a solid dispersion with consistent properties. PMID- 22299822 TI - Endogenous expansion of regulatory T cells leads to long-term islet graft survival in diabetic NOD mice. AB - Donor pancreatic lymph node cells (PLNC) protect islet transplants in Non-obese diabetic (NOD) mice. We hypothesized that induced FoxP3(+) regulatory T cells (Tregs) were required for long-term islet engraftment. NOD or NOD.NON mice were treated with ALS (antilymphocyte serum) and transplanted with NOR islets +/-PLNC (5 * 10(7) ). In vivo proliferation and expansion of FoxP3(+) Tregs was monitored in spleen and PLN from ALS- and ALS/PLNC-treated recipient mice. Anti CD25 depletion was used to determine the necessity of Tregs for tolerance. FoxP3(+) numbers significantly increased in ALS/PLNC-treated recipients compared to ALS-treated mice. In ALS/PLNC-treated mice, recipient-derived Tregs localized to the transplanted islets, and this was associated with intact, insulin producing beta cells. Proliferation and expansion of FoxP3(+) Tregs was markedly increased in PLNC-treated mice with accepted islet grafts, but not in diabetic mice not receiving PLNC. Deletion of Tregs with anti-CD25 antibodies prevented islet graft tolerance and resulted in rejection. Adoptive transfer of Tregs to secondary NOD.scid recipients inhibited autoimmunity by cotransferred NOD effector T cells. Treg expansion induced by ALS/PLNC-treatment promoted long term islet graft survival. Strategies leading to Treg proliferation and localization to the transplant site represent a therapeutic approach to controlling recurrent autoimmunity. PMID- 22299823 TI - Use of non-steroidal anti-inflammatory drugs in pregnancy: impact on the fetus and newborn. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed in pregnancy to treat fever, pain and inflammation. Indications for chronic use of these agents during pregnancy are inflammatory bowel or chronic rheumatic diseases. Since the seventies, NSAIDs have been used as effective tocolytic agents: indomethacin has been the reference drug, delaying delivery for at least 48 hours and up to 7-10 days. Additionally, self-medication with NSAIDs is practiced by pregnant women. NSAIDs given to pregnant women cross the placenta and may cause embryo-fetal and neonatal adverse effects, depending on the type of agent, the dose and duration of therapy, the period of gestation, and the time elapsed between maternal NSAID administration and delivery. These effects derive from the action mechanisms of NSAIDs (mainly inhibition of prostanoid activity) and from the physiological changes in drug pharmacokinetics occurring during pregnancy. Increased risks of miscarriage and malformations are associated with NSAID use in early pregnancy. Conversely, exposure to NSAIDs after 30 weeks' gestation is associated with an increased risk of premature closure of the fetal ductus arteriosus and oligohydramnios. Fetal and neonatal adverse effects affecting the brain, kidney, lung, skeleton, gastrointestinal tract and cardiovascular system have also been reported after prenatal exposure to NSAIDs. NSAIDs should be given in pregnancy only if the maternal benefits outweigh the potential fetal risks, at the lowest effective dose and for the shortest duration possible. This article discusses in detail the placental transfer and metabolism of NSAIDs, and the adverse impact of prenatal NSAID exposure on the offspring. PMID- 22299824 TI - Characterization of single nucleotide polymorphisms of cytochrome p450 in an Australian deceased sample. AB - The genetically variable CYP450 isozymes are responsible for the metabolism of up to 80% of commonly used drugs, many of which are detected in cases of unexpected or suspicious death in Australia. The aim of this study was to examine the genetic profiles of individuals in a cohort of Australian deceased individuals dying of drug toxicity (219), natural disease (150), external injury (109) or unascertained (8) causes, to determine if there was an over-representation of individuals with a genetic predisposition to altered drug metabolism in cases attributed to drug toxicity compared with other causes. Single nucleotide polymorphisms (SNP) of CYP1A2, 2C9, 2C19, 2D6, 3A4 and 3A5 were analyzed. There were 27 cases (6.1%) that were CYP2D6 poor metabolizers (PM) and an additional 8 cases (1.7 %) that were CYP2C19 PMs. Around 31% of the cases were CYP2D6 intermediate-poor metabolizers, with a number of cases exhibiting drug combinations that were likely to have caused pharmacokinetic or pharmacodynamic interactions. There was no correlation between cause of death type and CYP2D6 metabolizer status. Increased enzyme activity was also indicated by the presence of hyperinducible variants such as CYP1A2*1F, which was observed at a frequency of 48%. PMID- 22299825 TI - Optimisation of DMPK by the inhaled route: challenges and approaches. AB - The renewed interest in inhalation delivery over recent years has led to an expansion in the understanding of lung pharmacokinetics. Historically optimisation of inhaled drugs focused largely on development of material properties, consistent with achieving a good lung deposition, alongside demonstrating appropriate in vivo efficacy with little understanding of the relationship to pharmacokinetics in the lung. Recent efforts have led to an increased understanding of lung concentrations and how to maximise exposure in order to achieve the desired pharmacological response at a dose consistent with development of an inhaled product. Although there is a prerequisite for excellent potency in inhalation delivery, it is essential that this be combined with pharmacokinetic properties that allow sufficient free concentration at the effect site in lung to exert the pharmacological response for an appropriate dosing interval. Increases in basicity, polarity and/or decreases in aqueous solubility can extend pharmacokinetic duration and assist in finding the right balance between lung and systemic exposure. Current evidence suggests there are similarities in lung retention in rat and dog and that animal lung concentration data can enable pharmacokinetic-pharmacodynamic relationships to be derived thus providing more confidence in the requirements for man. Although inhaled delivery is challenging from a pharmacokinetic point of view, direct evaluation of exposure in the target organ has enabled further understanding of the drivers for drug disposition and highlighted the need for further development of predictive lung pharmacokinetic tools in the future. PMID- 22299826 TI - Illegal injection of industrial silicone oil for breast augmentation: risks, solutions and results. PMID- 22299827 TI - Emodin inhibits invasion and migration of prostate and lung cancer cells by downregulating the expression of chemokine receptor CXCR4. AB - Emodin (ED), an anthraquinone derivative, has been found to inhibit proliferation, induce apoptosis, suppress angiogenesis, impede metastasis, and enhance chemotherapy. However, the detailed mechanism of ED related to the regulation of CXC chemokine receptor-4 (CXCR4) gene expression that affects cellular migration and invasion in prostate and lung cancer cells are not fully understood. Recent evidence indicates that the CXCR4/CXCL12 axis is involved in promoting invasion and metastasis in tumors. Thus, novel agents that can downregulate CXCR4 expression have therapeutic potential in repressing cancer metastasis. Among ED and its derivatives, it is found that ED downregulated the expression of both CXCR4 and HER2 without affecting cell viability in tumor cells. The suppression of CXCR4 expression by ED was found to correlate with the inhibition of CXCL12-induced migration and invasion of both DU145 and A549 cells. Besides, neither proteasome inhibition nor lysosomal stabilization had any effect on ED-induced decrease in CXCR4 expression. The basic molecular mechanisms unveiled that the downregulation of CXCR4 was at the transcriptional level, as indicated by downregulation of mRNA expression and suppression of NF-kappaB activation. Overall, our findings suggest that ED is a novel blocker of CXCR4 expression and, thus, has enormous potential as a powerful therapeutic agent for metastatic cancer. PMID- 22299828 TI - Usefulness of live/real time three-dimensional transesophageal echocardiography in the assessment of severe mitral annuloplasty ring dehiscence. PMID- 22299829 TI - Lipocalin-type prostaglandin D synthase as a marker for the proliferative potential of melanocyte-lineage cells in the human skin. AB - Melanocytes in the human epidermis actively produce and secrete various substances, thereby contributing to the maintenance of the skin homeostasis. Lipocalin-type prostaglandin D synthase (L-PGDS) that catalyzes the formation of prostaglandin D(2) (PGD(2) ) may be one of such secreted molecules. Once secreted, L-PGDS functions as a transporter for lipophilic ligands, including all trans retinoic acid (RA). L-PGDS, therefore, may possess pleiotropic functions in the skin through PGD(2) and RA. We aimed to identify the cell types that express L-PGDS in human skin and to explore the role of L-PGDS in the growth potential of melanocyte-lineage cells. Immunohistochemical analysis for L-PGDS expression was performed with the tissue sections that were prepared from five malignant melanomas, six nevus cell nevi and one Spitz nevus. Normal skin tissues adjacent to the excised melanoma tissues were also analyzed. L-PGDS is expressed in epidermal melanocytes but its expression is undetectable in keratinocytes. Moreover, L-PGDS is undetectable in most benign nevus cells, which may reflect the marginally accelerated proliferation of nevus cells. In contrast, L-PGDS is overexpressed in malignant melanomas, although the frequency of L-PGDS-positive cells was variable (15-50%), depending on the specimens. Lastly, RNA interference analysis against human L-PGDS was performed with short interfering RNA. Knockdown of L-PGDS expression with short interfering RNA in cultured cells suggests that L PGDS may restrict cell proliferation through RA. In conclusion, L-PGDS expression may contribute to the restricted proliferation of epidermal melanocytes, but conversely its overexpression may reflect the dysregulated proliferation of melanoma cells. PMID- 22299830 TI - Service quality of private hospitals: the Iranian patients' perspective. AB - BACKGROUND: Highly competitive market in the private hospital industry has caused increasing pressure on them to provide services with higher quality. The aim of this study was to determine the different dimensions of the service quality in the private hospitals of Iran and evaluating the service quality from the patients' perspective. METHODS: A cross-sectional study was conducted between October and November 2010 in Tehran, Iran. The study sample was composed of 983 patients randomly selected from 8 private general hospitals. The study questionnaire was the SERVQUAL questionnaire, consisting of 21 items in service quality dimensions. RESULTS: The result of factor analysis revealed 3 factors, explaining 69% of the total variance. The total mean score of patients' expectation and perception was 4.91(SD = 0.2) and 4.02(SD = 0.6), respectively. The highest expectation and perception related to the tangibles dimension and the lowest expectation and perception related to the empathy dimension. The differences between perception and expectation were significant (p < 0.001). There was a significant difference between the expectations scores based on gender, education level, and previous hospitalization in that same hospital. Also, there was a significant difference between the perception scores based on insurance coverage, average length of stay, and patients' health conditions on discharge. CONCLUSION: The results showed that SERVQUAL is a valid, reliable, and flexible instrument to monitor and measure the quality of the services in private hospitals of Iran. Our findings clarified the importance of creating a strong relationship between patients and the hospital practitioners/personnel and the need for hospital staff to be responsive, credible, and empathetic when dealing with patients. PMID- 22299831 TI - Modification of TiO(2) nanotube surfaces by electro-spray deposition of amoxicillin combined with PLGA for bactericidal effects at surgical implantation sites. AB - OBJECTIVE: To fabricate the antibiotic-releasing coatings on TiO(2) nanotube surfaces for wide applications of implant and bone plate in medical and dental surgery, the optimal deposition time of amoxicillin/PLGA solution simultaneously performing non-toxicity and a high bactericidal effect for preventing early implant failures was found. MATERIALS AND METHODS: FE-SEM, ESD and FT-IR were used for confirming deposition of amoxicillin/PLGA on the TiO(2) surface. Also, the elution of amoxicillin/PLGA in a TiO(2) nanotube surface was measured by a UV VIS spectrophotometer. The bactericidal effect of amoxicillin on the TiO(2) nanotube surface was evaluated by using Staphylococcus aureus (S. aureus). The cytotoxicity and cell proliferation were observed by WST assay using MC3T3-E1 osteoblast cells. RESULTS: The results indicated that the TiO(2) nanotube surface controlled by electro-spray deposition time with amoxicillin/PLGA solution could provide a high bactericidal effect against S. aureus by the bactericidal effect of amoxicillin, as well as good osteoblast cell proliferation at the TiO(2) nanotube surface without toxicity. CONCLUSIONS: This study used electro-spray deposition (ESD) methodology to obtain amoxicillin deposition in nanotube structures of TiO(2) and found the optimal deposition time of amoxicillin/PLGA solution simultaneously performing non-toxicity and a high bactericidal effect for preventing early implant failures. PMID- 22299832 TI - Chronic pelvic pain: is it time for an algorithmic approach? PMID- 22299834 TI - Bioregeneration of activated carbon saturated with phenol. PMID- 22299833 TI - Ca2+ signals of astrocytes are modulated by the NAD+/NADH redox state. AB - Astrocytes are important glial cells in the brain providing metabolic support to neurons as well as contributing to brain signaling. These different functional levels have to be highly coordinated to allow for proper cell and brain function. In this study, we show that in astrocytes the NAD(+) /NADH redox state modulates dopamine-induced Ca(2+) signals thereby connecting metabolism and Ca(2+) signaling. Application of dopamine induced a dose-dependent increase in Ca(2+) signal frequency in these cells, which was dependent on D(1) -receptor signaling, glycolytic activity, an increase in cytosolic NADH and inositol 1,4,5 triphosphate receptor operated intracellular Ca(2+) stores. Application of dopamine at a low concentration (1 MUM) did not induce an increase in Ca(2+) signal frequency by itself. However, simultaneously increasing cytosolic NADH content either by direct application of NADH or by application of lactate resulted in a pronounced increase in Ca(2+) signal frequency. This increase could be blocked by co-application of pyruvate, suggesting that indeed the NAD(+) /NADH redox state is regulating Ca(2+) signals. We conclude that at the NAD(+) /NADH redox state metabolic and signaling information is integrated in astrocytes, thereby most likely contributing to precisely coordinate these different tasks of astrocytes. PMID- 22299835 TI - Decomposition of organic matter in lake sediments. PMID- 22299836 TI - Elemental partitioning in ash depositories and material balance for a coal burning facility by spark source mass spectrometry. PMID- 22299837 TI - Physicochemical properties controlling polychlorinated biphenyl (PCB) concentrations in aquatic organisms. PMID- 22299839 TI - Fish/sediment concentration ratios for organic compounds. PMID- 22299838 TI - Retrospective analysis of the response of Saginaw Bay, Lake Huron, to reductions in phosphorus loadings. PMID- 22299840 TI - Characterization of individual particles in the Phoenix urban aerosol, using electron beam instruments. PMID- 22299841 TI - Nonreversible sorption of phenolic compounds by sediment fractions: the role of sediment organic matter. PMID- 22299843 TI - Adsorptive displacement from activated carbon: recovery of 4,4' dichlorobiphenyl. PMID- 22299842 TI - Atmospheric reactions of N-nitrosodimethylamine and dimethylnitramine. PMID- 22299844 TI - X-ray photoemission spectroscopy of environmental particles. PMID- 22299845 TI - Reply on comment on Acid fog. PMID- 22299846 TI - Comment on "acid fog". PMID- 22299851 TI - Communication: improving the density functional theory+U description of CeO2 by including the contribution of the O 2p electrons. AB - Density functional theory (DFT) based approaches within the local-density approximation or generalized gradient approximation frameworks fail to predict the correct electron localization in strongly correlated systems due to the lack of cancellation of the Coulomb self-interaction. This problem might be circumvented either by using hybrid functionals or by introducing a Hubbard-like term to account for the on site interactions. This latter DFT+U approach is less expensive and therefore more practical for extensive calculations in solid-state computational simulations. By and large, the U term only affects the metal electrons, in our case the Ce 4f ones. In the present work, we report a systematic analysis of the effect of adding such a U term also to the oxygen 2p electrons. We find that using a set of U(f) = 5 eV and U(p) = 5eV effective terms leads to improved description of the lattice parameters, band gaps, and formation and reduction energies of CeO(2). PMID- 22299852 TI - Communication: crystallite nucleation in supercooled glycerol near the glass transition. AB - Heterogeneity and solid-like structures found near the glass transition provide a key to a better understanding of supercooled liquids and of the glass transition. However, the formation of solid-like structures and its effect on spatial heterogeneity in supercooled liquids is neither well documented nor well understood. In this work, we reveal the crystalline nature of the solid-like structures in supercooled glycerol by means of neutron scattering. The results indicate that inhomogeneous nucleation happens at temperatures near T(g). Nevertheless, the thermal history of the sample is essential for crystallization. This implies such structures in supercooled liquids strongly depend on thermal history. Our work suggests that different thermal histories may lead to different structures and therefore to different length and time scales of heterogeneity near the glass transition. PMID- 22299853 TI - Communication: a chemically accurate global potential energy surface for the HO + CO -> H + CO2 reaction. AB - We report a chemically accurate global potential energy surface for the HOCO system based on high-level ab initio calculations at ~35,000 points. The potential energy surface is shown to reproduce important stationary points and minimum energy paths. Quasi-classical trajectory calculations indicated a good agreement with experimental data. PMID- 22299854 TI - Communication: correlation of the instantaneous and the intermediate-time elasticity with the structural relaxation in glassforming systems. AB - The elastic models of the glass transition relate the increasing solidity of the glassforming systems with the huge slowing down of the structural relaxation and the viscous flow. The solidity is quantified in terms of the instantaneous shear modulus G(infinity), i.e., the immediate response to a step change in the strain. By molecular-dynamics simulations of a model polymer system, one shows the virtual absence of correlations between the instantaneous elasticity and the structural relaxation. Instead, a well-defined scaling is evidenced by considering the elastic response observed at intermediate times after the initial fast stress relaxation. The scaling regime ranges from sluggish states with virtually pure elastic response on the picosecond time scale up to high-mobility states where fast restructuring events are more apparent. PMID- 22299855 TI - The coupled cluster singles, doubles, and a hybrid treatment of connected triples based on the split virtual orbitals. AB - We have proposed a simple strategy for splitting the virtual orbitals with a large basis set into two subgroups (active and inactive) by taking a smaller basis set as an auxiliary basis set. With the split virtual orbitals (SVOs), triple or higher excitations can be partitioned into active and inactive subgroups (according to the number of active virtual orbitals involved), which can be treated with different electron correlation methods. In this work, the coupled cluster (CC) singles, doubles, and a hybrid treatment of connected triples based on the SVO [denoted as SVO-CCSD(T)-h], has been implemented. The present approach has been applied to study the bond breaking potential energy surfaces in three molecules (HF, F(2), and N(2)), and the equilibrium properties in a number of open-shell diatomic molecules. For all systems under study, the SVO-CCSD(T)-h method based on the unrestricted Hartree-Fock (UHF) reference is an excellent approximation to the corresponding CCSDT (CC singles, doubles, and triples), and much better than the UHF-based CCSD(T) (CC singles, doubles, and perturbative triples). On the other hand, the SVO-CCSD(T)-h method based on the restricted HF (RHF) reference can also provide considerable improvement over the RHF-based CCSD(T). PMID- 22299856 TI - Prediction of reaction barriers and force-induced instabilities under mechanochemical conditions with an approximate model: a case study of the ring opening of 1,3-cyclohexadiene. AB - Mechanochemistry, the use of mechanical stresses to activate chemical reactions, has emerged as a topic of significant interest. The present study examines the use of an approximate model for the prediction of reaction barriers under mechanochemical conditions using the ring opening of 1,3-cyclohexadiene along conrotatory and disrotatory directions as a specific test case. To do this, reaction barriers are evaluated using quantum chemical methods with an external force applied between various pairs of atoms. The results show that the consequent effects on the barrier exhibit a significant dependence on the locations of the atoms used to apply the external force, and in some cases, force induced instabilities occur that alter the fundamental nature of the reaction pathway. The ability of an approximate model based on a second-order expansion of the force-modified potential energy with respect to nuclear coordinates to reproduce this behavior is then assessed. Good agreement between the results obtained through the quantum chemical calculations and approximate model is attained when force-induced instabilities do not occur. In addition, a strategy for predicting when such instabilities occur is presented and found to yield results that are in qualitative agreement with the quantum chemical calculations. Finally, the response of the system to the external force is interpreted in terms of the parameters entering the model, which correspond to interatomic distances and stiffnesses, and possibly sheds lights on ways to design molecules that exhibit a desired chemical response to mechanochemical conditions. PMID- 22299857 TI - Generalized essential energy space random walks to more effectively accelerate solute sampling in aqueous environment. AB - Molecular dynamics sampling can be enhanced via the promoting of potential energy fluctuations, for instance, based on a Hamiltonian modified with the addition of a potential-energy-dependent biasing term. To overcome the diffusion sampling issue, which reveals the fact that enlargement of event-irrelevant energy fluctuations may abolish sampling efficiency, the essential energy space random walk (EESRW) approach was proposed earlier. To more effectively accelerate the sampling of solute conformations in aqueous environment, in the current work, we generalized the EESRW method to a two-dimension-EESRW (2D-EESRW) strategy. Specifically, the essential internal energy component of a focused region and the essential interaction energy component between the focused region and the environmental region are employed to define the two-dimensional essential energy space. This proposal is motivated by the general observation that in different conformational events, the two essential energy components have distinctive interplays. Model studies on the alanine dipeptide and the aspartate-arginine peptide demonstrate sampling improvement over the original one-dimension-EESRW strategy; with the same biasing level, the present generalization allows more effective acceleration of the sampling of conformational transitions in aqueous solution. The 2D-EESRW generalization is readily extended to higher dimension schemes and employed in more advanced enhanced-sampling schemes, such as the recent orthogonal space random walk method. PMID- 22299858 TI - Molecular properties via a subsystem density functional theory formulation: a common framework for electronic embedding. AB - In this article, we present a consistent derivation of a density functional theory (DFT) based embedding method which encompasses wave-function theory-in-DFT (WFT-in-DFT) and the DFT-based subsystem formulation of response theory (DFT-in DFT) by Neugebauer [J. Neugebauer, J. Chem. Phys. 131, 084104 (2009)] as special cases. This formulation, which is based on the time-averaged quasi-energy formalism, makes use of the variation Lagrangian techniques to allow the use of non-variational (in particular: coupled cluster) wave-function-based methods. We show how, in the time-independent limit, we naturally obtain expressions for the ground-state DFT-in-DFT and WFT-in-DFT embedding via a local potential. We furthermore provide working equations for the special case in which coupled cluster theory is used to obtain the density and excitation energies of the active subsystem. A sample application is given to demonstrate the method. PMID- 22299859 TI - Increasing the applicability of density functional theory. II. Correlation potentials from the random phase approximation and beyond. AB - Density functional theory (DFT) results are mistrusted at times due to the presence of an unknown exchange correlation functional, with no practical way to guarantee convergence to the right answer. The use of a known exchange correlation functional based on wave-function theory helps to alleviate such mistrust. The exchange correlation functionals can be written exactly in terms of the density-density response function using the adiabatic-connection and fluctuation-dissipation framework. The random phase approximation (RPA) is the simplest approximation for the density-density response function. Since the correlation functional obtained from RPA is equivalent to the direct ring coupled cluster doubles (ring-CCD) correlation functional, meaning only Coulomb interactions are included, one can bracket RPA between many body perturbation theory (MBPT)-2 and CCD with the latter having all ring, ladder, and exchange contributions. Using an optimized effective potential strategy, we obtain correlation potentials corresponding to MBPT-2, RPA (ring-CCD), linear-CCD, and CCD. Using the suitable choice of the unperturbed Hamiltonian, Kohn-Sham self consistent calculations are performed. The spatial behavior of the resulting potentials, total energies, and the HOMO eigenvalues are compared with the exact values for spherical atoms. Further, we demonstrate that the self-consistent eigenvalues obtained from these consistent potentials used in ab initio dft approximate all principal ionization potentials as demanded by ionization potential theorem. PMID- 22299860 TI - The electric double layer structure around charged spherical interfaces. AB - We derive a formally simple approximate analytical solution to the Poisson Boltzmann equation for the spherical system via a geometric mapping. Its regime of applicability in the parameter space of the spherical radius and the surface potential is determined, and its superiority over the linearized solution is demonstrated. PMID- 22299861 TI - Coherently controlled molecular junctions. AB - Within a generic model, we discuss the possibility of coherent control of charge fluxes in unbiased molecular junctions. The control is induced by resonances between the Rabi frequency due to a pumping laser field and internal characteristic frequencies of pre-designed molecular donor-bridge-acceptor complexes. Two models are considered: a coherently controlled molecular charge pump and a molecular switch. The study generalizes previous consideration of light induced current [M. Galperin and A. Nitzan, Phys. Rev. Lett. 95, 206802 (2005)] and of a molecular electron pump [R. Volkovich and U. Peskin, Phys. Rev. B 83, 033403 (2011)] and accounts for the coherently driven charge transport in an unbiased molecular junction with symmetric coupling to leads. Numerical examples demonstrate the feasibility of the control mechanism for realistic junctions parameters. PMID- 22299862 TI - Parallel density matrix propagation in spin dynamics simulations. AB - Several methods for density matrix propagation in parallel computing environments are proposed and evaluated. It is demonstrated that the large communication overhead associated with each propagation step (two-sided multiplication of the density matrix by an exponential propagator and its conjugate) may be avoided and the simulation recast in a form that requires virtually no inter-thread communication. Good scaling is demonstrated on a 128-core (16 nodes, 8 cores each) cluster. PMID- 22299863 TI - Robust interpolation between weak- and strong-correlation regimes of quantum systems. AB - A robust interpolation between the weak- and strong-correlation regimes of quantum systems is presented. It affords approximants to the function E(omega) describing the dependence of the total energy (or other observable) on the coupling parameter omega that measures the correlation strength. The approximants conform to truncations of the asymptotic expansions of E(omega) at the omega -> 0 and omega -> infinity limits with arbitrary (but given) numbers of terms. In addition, depending on the number of fitted parameters, they either reproduce or optimally (in the least-square or maximum-error sense) approximate the exact E(omega) at any given number of values of the coupling strength. Numerical tests demonstrate the high accuracy of even the low-order approximate expression for E(omega). The approximants, which do not suffer from spurious poles, possess a wide range of applicability that stems from their capability of accurately reproducing not only E(omega) but also its derivatives with respect to omega. They are equally useful for interpolation between the low- and high-temperature limits of energy and other quantities associated with various models of statistical thermodynamics. The new interpolation scheme is not applicable to the cases where the weak- and strong-correlation asymptotics involve non-analytic functions of omega or expressions dependent on logarithm of the coupling strength. Excluded are also the cases where the weak- and strong-correlation asymptotics pertain to de facto different states, e.g., the ground state of a homogeneous electron gas in three dimensions. PMID- 22299864 TI - Influence of structure in heterodyne electrophoretic light scattering. AB - Heterodyne light scattering is employed to probe the electrophoretic flow behavior of a concentrated, deionized model colloidal suspension. Both for the fluid and crystalline regime, the power spectra are well described as velocity distributions, which let assume that the power spectra are dominated by the self dynamic structure factor. Furthermore, all measured power spectra show an increase of the frequency integrated intensity with the electric field. Since the number of particles should remain constant this finding is unexpected. These effects are rationalized on the basis of a new theoretical model including the influence of the structure factor and of the mobility polydispersity on the power spectra. PMID- 22299865 TI - Experimental verification of strong rotational dependence of fluorescence and predissociation yield in the b1Piu(v = 1) level of 14N2. AB - New, rotationally resolved fluorescence-excitation spectra confirm coupled channel Schrodinger-equation predictions of strong rotational dependence of the fluorescence and predissociation yields in the b(v = 1) level of (14)N(2). PMID- 22299866 TI - Gas-phase photodissociation of CH3COCN at 308 nm by time-resolved Fourier transform infrared emission spectroscopy. AB - By using time-resolved Fourier-transform infrared emission spectroscopy, the fragments of HCN(v = 1, 2) and CO(v = 1-3) are detected in one-photon dissociation of acetyl cyanide (CH(3)COCN) at 308 nm. The S(1)(A(")), (1)(n(O), pi(*) (CO)) state at 308 nm has a radiative lifetime of 0.46 +/- 0.01 MUs, long enough to allow for Ar collisions that induce internal conversion and enhance the fragment yields. The rate constant of Ar collision-induced internal conversion is estimated to be (1-7) * 10(-12) cm(3) molecule(-1) s(-1). The measurements of O(2) dependence exclude the production possibility of these fragments via intersystem crossing. The high-resolution spectra of HCN and CO are analyzed to determine the ro-vibrational energy deposition of 81 +/- 7 and 32 +/- 3 kJ/mol, respectively. With the aid of ab initio calculations, a two-body dissociation on the energetic ground state is favored leading to HCN + CH(2)CO, in which the CH(2)CO moiety may further undergo secondary dissociation to release CO. The production of CO(2) in the reaction with O(2) confirms existence of CH(2) and a secondary reaction product of CO. The HNC fragment is identified but cannot be assigned, as restricted to a poor signal-to-noise ratio. Because of insufficient excitation energy at 308 nm, the CN and CH(3) fragments that dominate the dissociation products at 193 nm are not detected. PMID- 22299867 TI - Phase-only shaped laser pulses in optimal control theory: application to indirect photofragmentation dynamics in the weak-field limit. AB - We implement phase-only shaped laser pulses within quantum optimal control theory for laser-molecule interaction. This approach is applied to the indirect photofragmentation dynamics of NaI in the weak-field limit. It is shown that optimized phase-modulated pulses with a fixed frequency distribution can substantially modify transient dissociation probabilities as well as the momentum distribution associated with the relative motion of Na and I. PMID- 22299868 TI - Vibrational energy relaxation of benzene dimer and trimer in the CH stretching region studied by picosecond time-resolved IR-UV pump-probe spectroscopy. AB - Vibrational energy relaxation (VER) of the Fermi polyads in the CH stretching vibration of the benzene dimer (Bz(2)) and trimer (Bz(3)) has been investigated by picosecond (ps) time-resolved IR-UV pump-probe spectroscopy in a supersonic beam. The vibrational bands in the 3000-3100 cm(-1) region were excited by a ps IR pulse and the time evolutions at the pumped and redistributed (bath) levels were probed by resonance enhanced multiphoton ionization with a ps UV pulse. For Bz(2), a site-selective excitation in the T-shaped structure was achieved by using the isotope-substituted heterodimer hd, where h = C(6)H(6) and d = C(6)D(6), and its result was compared with that of hh homodimer. In the hd heterodimer, the two isomers, h(stem)d(top) and h(top)d(stem), show remarkable site-dependence of the lifetime of intracluster vibrational energy redistribution (IVR); the lifetime of the Stem site [h(stem)d(top), 140-170 ps] is ~2.5 times shorter than that of the Top site [h(top)d(stem), 370-400 ps]. In the transient UV spectra, a broad electronic transition due to the bath modes emerges and gradually decays with a nanosecond time scale. The broad transition shows different time profile depending on UV frequency monitored. These time profiles are described by a three-step VER model involving IVR and vibrational predissociation: initial -> bath1(intramolecular) -> bath2(intermolecular) -> fragments. This model also describes well the observed time profile of the Bz fragment. The hh homodimer shows the stepwise VER process with time constants similar to those of the hd dimer, suggesting that the excitation-exchange coupling of the vibrations between the two sites is very weak. Bz(3) also exhibited the stepwise VER process, though each step is faster than Bz(2). PMID- 22299869 TI - Mid-infrared spectroscopy of molecular ions in helium nanodroplets. AB - High resolution IR spectra of aniline, styrene, and 1,1-diphenylethylene cations embedded in superfluid helium nanodroplets have been recorded in the 300-1700 cm( 1) range using a free-electron laser as radiation source. Comparison of the spectra with available gas phase data reveals that the helium environment induces no significant matrix shift nor leads to an observable line broadening of the resonances. In addition, the IR spectra have provided new and improved vibrational transition frequencies for the cations investigated, as well as for neutral aniline and styrene. Indications have been found that the ions desolvate from the droplets after excitation by a non-evaporative process in which they are ejected from the helium droplets. The kinetic energy of the ejected ions is found to be ion specific and to depend only weakly on the excitation energy. PMID- 22299870 TI - Microwave, infrared and Raman spectra, r0 structural parameters, ab initio calculations and vibrational assignment of 1-fluoro-1-silacyclopentane. AB - The microwave spectrum (6500-18 ,500 MHz) of 1-fluoro-1-silacyclopentane, c C(4)H(8)SiHF has been recorded and 87 transitions for the (28)Si, (29)Si, (30)Si, and (13)C isotopomers have been assigned for a single conformer. Infrared spectra (3050-350 cm(-1)) of the gas and solid and Raman spectrum (3100-40 cm(-1)) of the liquid have also been recorded. The vibrational data indicate the presence of a single conformer with no symmetry which is consistent with the twist form. Ab initio calculations with a variety of basis sets up to MP2(full)/aug-cc-pVTZ predict the envelope-axial and envelope-equatorial conformers to be saddle points with nearly the same energies but much lower energy than the planar conformer. By utilizing the microwave rotational constants for seven isotopomers ((28)Si, (29)Si, (30)Si, and four (13)C) combined with the structural parameters predicted from the MP2(full)/6-311+G(d,p) calculations, adjusted r(0) structural parameters have been obtained for the twist conformer. The heavy atom distances in A are: r(0)(SiC(2)) = 1.875(3); r(0)(SiC(3)) = 1.872(3); r(0)(C(2)C(4)) = 1.549(3); r(0)(C(3)C(5)) = 1.547(3); r(0)(C(4)C(5)) = 1.542(3); r(0)(SiF) = 1.598(3) and the angles in degrees are: [angle]CSiC = 96.7(5); [angle]SiC(2)C(4) = 103.6(5); [angle]SiC(3)C(5) = 102.9(5); [angle]C(2)C(4)C(5) = 108.4(5); [angle]C(3)C(5)C(4) = 108.1(5); [angle]F(6)Si(1)C(2) = 110.7(5); [angle]F(6)Si(1)C(3) = 111.6(5). The heavy atom ring parameters are compared to the corresponding r(s) parameters. Normal coordinate calculations with scaled force constants from MP2(full)/6 31G(d) calculations were carried out to predict the fundamental vibrational frequencies, infrared intensities, Raman activities, depolarization values, and infrared band contours. These experimental and theoretical results are compared to the corresponding quantities of some other five-membered rings. PMID- 22299871 TI - Accurate ab initio potential energy surface, thermochemistry, and dynamics of the Cl(2P, 2P(3/2) + CH4 -> HCl + CH3 and H + CH3Cl reactions. AB - We report a high-quality, ab initio, full-dimensional global potential energy surface (PES) for the Cl((2)P, (2)P(3/2)) + CH(4) reaction, which describes both the abstraction (HCl + CH(3)) and substitution (H + CH(3)Cl) channels. The analytical PES is a least-squares fit, using a basis of permutationally invariant polynomials, to roughly 16,000 ab initio energy points, obtained by an efficient composite method, including counterpoise and spin-orbit corrections for the entrance channel. This composite method is shown to provide accuracy almost equal to all-electron CCSD(T)/aug-cc-pCVQZ results, but at much lower computational cost. Details of the PES, as well as additional high-level benchmark characterization of structures and energetics are reported. The PES has classical barrier heights of 2650 and 15,060 cm(-1) (relative to Cl((2)P(3/2)) + CH(4)(eq)), respectively, for the abstraction and substitution reactions, in good agreement with the corresponding new computed benchmark values, 2670 and 14,720 cm(-1). The PES also accurately describes the potential wells in the entrance and exit channels for the abstraction reaction. Quasiclassical trajectory calculations using the PES show that (a) the inclusion of the spin-orbit corrections in the PES decreases the cross sections by a factor of 1.5-2.5 at low collision energies (E(coll)); (b) at E(coll) ~ 13,000 cm(-1) the substitution channel opens and the H/HCl ratio increases rapidly with E(coll); (c) the maximum impact parameter (b(max)) for the abstraction reaction is ~6 bohr; whereas b(max) is only ~2 bohr for the substitution; (d) the HCl and CH(3) products are mainly in the vibrational ground state even at very high E(coll); and (e) the HCl rotational distributions are cold, in excellent agreement with experiment at E(coll) = 1280 cm(-1). PMID- 22299872 TI - Ultraviolet photodissociation dynamics of the phenyl radical. AB - Ultraviolet (UV) photodissociation dynamics of jet-cooled phenyl radicals (C(6)H(5) and C(6)D(5)) are studied in the photolysis wavelength region of 215 268 nm using high-n Rydberg atom time-of-flight and resonance enhanced multiphoton ionization techniques. The phenyl radicals are produced from 193-nm photolysis of chlorobenzene and bromobenzene precursors. The H-atom photofragment yield spectra have a broad peak centered around 235 nm and are in good agreement with the UV absorption spectra of phenyl. The H + C(6)H(4) product translational energy distributions, P(E(T))'s, peak near ~7 kcal/mol, and the fraction of average translational energy in the total excess energy, , is in the range of 0.20-0.35 from 215 to 268 nm. The H-atom product angular distribution is isotropic. The dissociation rates are in the range of 10(7)-10(8) s(-1) with internal energy from 30 to 46 kcal/mol above the threshold of the lowest energy channel H + o-C(6)H(4) (ortho-benzyne), comparable with the rates from the Rice Ramsperger-Kassel-Marcus theory. The results from the fully deuterated phenyl radical are identical. The dissociation mechanism is consistent with production of H + o-C(6)H(4), as the main channel from unimolecular decomposition of the ground electronic state phenyl radical following internal conversion of the electronically excited state. PMID- 22299873 TI - Unimolecular thermal decomposition of phenol and d5-phenol: direct observation of cyclopentadiene formation via cyclohexadienone. AB - The pyrolyses of phenol and d(5)-phenol (C(6)H(5)OH and C(6)D(5)OH) have been studied using a high temperature, microtubular (MUtubular) SiC reactor. Product detection is via both photon ionization (10.487 eV) time-of-flight mass spectrometry and matrix isolation infrared spectroscopy. Gas exiting the heated reactor (375 K-1575 K) is subject to a free expansion after a residence time in the MUtubular reactor of approximately 50-100 MUs. The expansion from the reactor into vacuum rapidly cools the gas mixture and allows the detection of radicals and other highly reactive intermediates. We find that the initial decomposition steps at the onset of phenol pyrolysis are enol/keto tautomerization to form cyclohexadienone followed by decarbonylation to produce cyclopentadiene; C(6)H(5)OH -> c-C(6)H(6) = O -> c-C(5)H(6) + CO. The cyclopentadiene loses a H atom to generate the cyclopentadienyl radical which further decomposes to acetylene and propargyl radical; c-C(5)H(6) -> c-C(5)H(5) + H -> HC=CH + HCCCH(2). At higher temperatures, hydrogen loss from the PhO-H group to form phenoxy radical followed by CO ejection to generate the cyclopentadienyl radical likely contributes to the product distribution; C(6)H(5)O-H -> C(6)H(5)O + H -> c C(5)H(5) + CO. The direct decarbonylation reaction remains an important channel in the thermal decomposition mechanisms of the dihydroxybenzenes. Both catechol (o-HO-C(6)H(4)-OH) and hydroquinone (p-HO-C(6)H(4)-OH) are shown to undergo decarbonylation at the onset of pyrolysis to form hydroxycyclopentadiene. In the case of catechol, we observe that water loss is also an important decomposition channel at the onset of pyrolysis. PMID- 22299874 TI - The ultraviolet photodissociation of CS2: the S(1D2) channel. AB - The photodissociation of CS(2) has been investigated using velocity-map ion imaging of the S((1)D(2)) atomic photofragments following excitation at 193 nm and at longer wavelengths close to the S((1)D(2)) channel threshold. The experiments probe regions both above and below the energetic barrier to linearity on the (1)Sigma(u) (+)((1)B(2)) potential energy surface. The imaging data in both regions indicate that the electronic angular momentum of the S((1)D(2)) atom products is unpolarized, but also reveal different dissociation dynamics in the two regions. Excitation above the barrier to linearity yields an inverted CS((1)Sigma(+)) vibrational population distribution, whereas the long-wavelength state-to-state results following excitation below the barrier reveal CS((1)Sigma(+))(v, J) coproduct state distributions which are consistent with a statistical partitioning of the energy. Below the barrier, photofragment excitation spectra point to an enhancement of the singlet channel for K = 1, relative to K = 0, where K is the projection of the angular momentum along the principal axis, in agreement with previous work. However, the CS cofragment product state distributions are found to be insensitive to K. It is proposed that dissociation below the barrier to linearity occurs primarily on a surface with a significant potential energy well and without an exit channel barrier, such as that for the ground electronic state. However, oscillatory structure is also observed in the kinetic energy release distributions, which is shown to be consistent with a mapping of parent molecule bending motion. This could indicate the operation of competing direct and indirect dissociation mechanisms below the barrier to linearity. PMID- 22299876 TI - Tungsten monocarbide, WC: pure rotational spectrum and 13C hyperfine interaction. AB - The J = 1->2 pure rotational transitions in the X(3)Delta(1)(nu = 0) state of (186)W(12)C and (184)W(12)C were recorded using a pump/probe microwave optical double resonance (PPMODR) technique and analyzed to give fine structure parameters. The field-free [17.6]2<-X(3)Delta(1) (1, 0) bands of the W(13)C isotopologues were recorded using laser induced fluorescence and analyzed to produce the (13)C(I = 1/2) magnetic hyperfine parameter. Bonding in the [17.6]2(nu = 1) and X(3)Delta(1)(nu = 0) states is discussed and a comparison of the experimentally determined properties of the X(3)Delta(1)(nu = 0) state with those predicted as a prelude to the electron electric dipole moment (eEDM) measurements [J. Lee, E. R. Meyer, R. Paudel, J. L. Bohn, and A. E. Leanhardt, J. Mod. Opt. 56, 2005 (2009)] is given. PMID- 22299875 TI - 17O excess transfer during the NO2 + O3 -> NO3 + O2 reaction. AB - The ozone molecule possesses a unique and distinctive (17)O excess (Delta(17)O), which can be transferred to some of the atmospheric molecules via oxidation. This isotopic signal can be used to trace oxidation reactions in the atmosphere. However, such an approach depends on a robust and quantitative understanding of the oxygen transfer mechanism, which is currently lacking for the gas-phase NO(2) + O(3) reaction, an important step in the nocturnal production of atmospheric nitrate. In the present study, the transfer of Delta(17)O from ozone to nitrate radical (NO(3)) during the gas-phase NO(2) + O(3) -> NO(3) + O(2) reaction was investigated in a series of laboratory experiments. The isotopic composition (delta(17)O, delta(18)O) of the bulk ozone and the oxygen gas produced in the reaction was determined via isotope ratio mass spectrometry. The Delta(17)O transfer function for the NO(2) + O(3) reaction was determined to be: Delta(17)O(O(3)*) = (1.23 +/- 0.19) * Delta(17)O(O(3))(bulk) + (9.02 +/- 0.99). The intramolecular oxygen isotope distribution of ozone was evaluated and results suggest that the excess enrichment resides predominantly on the terminal oxygen atoms of ozone. The results obtained in this study will be useful in the interpretation of high Delta(17)O values measured for atmospheric nitrate, thus leading to a better understanding of the natural cycling of atmospheric reactive nitrogen. PMID- 22299877 TI - New view of the ICN A continuum using photoelectron spectroscopy of ICN-. AB - Negative-ion photoelectron spectroscopy of ICN(-) (X (2)Sigma(+)) reveals transitions to the ground electronic state (X (1)Sigma(+)) of ICN as well as the first five excited states ((3)Pi(2), (3)Pi(1), Pi(0(-) ) (3), Pi(0(+) ) (3), and (1)Pi(1)) that make up the ICN A continuum. By starting from the equilibrium geometry of the anion, photoelectron spectroscopy characterizes the electronic structure of ICN at an elongated I-C bond length of 2.65 A. Because of this bond elongation, the lowest three excited states of ICN ((3)Pi(2), (3)Pi(1), and Pi(0( ) ) (3)) are resolved for the first time in the photoelectron spectrum. In addition, the spectrum has a structured peak that arises from the frequently studied conical intersection between the Pi(0(+) ) (3) and (1)Pi(1) states. The assignment of the spectrum is aided by MR-SO-CISD calculations of the potential energy surfaces for the anion and neutral ICN electronic states, along with calculations of the vibrational levels supported by these states. Through thermochemical cycles involving spectrally narrow transitions to the excited states of ICN, we determine the electron affinity, EA(ICN), to be 1.34(5) (+0.04/ 0.02) eV and the anion dissociation energy, D(0)(X (2)Sigma(+) I-CN(-)), to be 0.83 (+0.04/-0.02) eV. PMID- 22299878 TI - Product angular distributions in the ultraviolet photodissociation of N2O. AB - The angular distribution of products from the ultraviolet photodissociation of nitrous oxide yielding O((1)D) and N(2)(X Sigma(g)(+)(1)) was investigated using classical trajectory calculations. The calculations modeled absorption only to the 2(1)A(') electronic state but used surface-hopping techniques to model nonadiabatic transitions to the ground electronic state late in the dissociation. Observed values of the anisotropy parameter beta, which decrease as the product N(2) rotational quantum number j increases, could be well reproduced. The relatively low observed beta values arise principally from nonaxial recoil due to the very strong bending forces present in the excited state. In the main part of the product rotational distribution near 203 nm, an unusual dynamical effect produces the decrease in beta with increasing j; nonaxial recoil effects remain approximately constant while higher j product molecules arise from parent molecules that had their transition dipole moments aligned more closely along the molecular axis. In both low and high j tails of the rotational distribution, the variations in beta with j are caused by changes in the extent of nonaxial recoil. In the high-j tail, additional torque present on the ground state potential energy surface following nonadiabatic transitions causes both the additional rotational excitation and the lower beta values. PMID- 22299879 TI - Semiclassical glory analyses in the time domain for the H + D2(v(i) = 0, j(i) = 0) -> HD(v(f) = 3, j(f) = 0) + D reaction. AB - We make the first application of semiclassical (SC) techniques to the plane wavepacket formulation of time-domain (T-domain) scattering. The angular scattering of the state-to-state reaction, H + D(2)(v(i) = 0, j(i) = 0) -> HD(v(f) = 3, j(f) = 0) + D, is analysed, where v and j are vibrational and rotational quantum numbers, respectively. It is proved that the forward-angle scattering in the T-domain, which arises from a delayed mechanism, is an example of a glory. The SC techniques used in the T-domain are: An integral transitional approximation, a semiclassical transitional approximation, a uniform semiclassical approximation (USA), a primitive semiclassical approximation and a classical semiclassical approximation. Nearside-farside (NF) scattering theory is also employed, both partial wave and SC, since a NF analysis provides valuable insights into oscillatory structures present in the full scattering pattern. In addition, we incorporate techniques into the SC theory called "one linear fit" and "two linear fits", which allow the derivative of the quantum deflection function, Theta(')(J), to be estimated when ThetaJ exhibits undulations as a function of J, the total angular momentum variable. The input to our SC analyses is numerical scattering (S) matrix data, calculated from accurate quantum collisional calculations for the Boothroyd-Keogh-Martin-Peterson potential energy surface No. 2, in the energy domain (E-domain), from which accurate S matrix elements in the T-domain are generated. In the E-domain, we introduce a new technique, called "T-to-E domain SC analysis." It half-Fourier transforms the E domain accurate quantum scattering amplitude to the T-domain, where we carry out a SC analysis; this is followed by an inverse half-Fourier transform of the T domain SC scattering amplitude back to the E-domain. We demonstrate that T-to-E USA differential cross sections (DCSs) agree well with exact quantum DCSs at forward angles, for energies where a direct USA analysis in the E-domain fails. PMID- 22299880 TI - A theoretical study of the CX2N radicals (X = F, Cl, Br): the effect of halogen substitution on structure, isomerization, and energetics. AB - Structural isomers of the CX(2)N radicals, where X = F, Cl, and Br, have been investigated at high level of theory, i.e., using the coupled-cluster method in conjunction with correlation-consistent basis sets ranging in size from triple- to sextuple-zeta. Extrapolation to the complete basis-set limit as well as core correlation effects and inclusion of higher excitations in the cluster operator have been considered for accurately evaluating geometries and energies. The effect of halogen substitution on molecular structure, isomer stability, and dissociation energy is addressed; in particular, only the F(2)CN, Cl(2)CN, Br(2)CN, and F(2)NC radicals of C(2V) symmetry are predicted to be stable with respect to dissociation. PMID- 22299881 TI - Low-energy rotational inelastic collisions of H(+) + CO system. AB - The quantum mechanical state-to-state rotational excitation cross sections have been computed using the ab initio ground electronic state potential energy surface of the system [M. Mladenovic and S. Schmatz, J. Chem. Phys. 109, 4456 (1998)] computed at coupled-cluster single and double and triple perturbative excitations method using correlation-consistent polarized valence quadruple zeta basis set where the asymptotic potential have been computed using the dipole moment, quadrupole moment, and the molecular polarizability components and fitted to this interaction potential. The anisotropy of the surface has been analyzed in terms of the multipolar expansion coefficients for the rigid-rotor surface. The integral cross sections for rotational excitations have been computed by solving close-coupled equations at very low collision energies (5-200 cm(-1)) and the corresponding rates have been obtained for a range of low temperatures (5-175 K). The j = 0 -> j(') = 1 rotational excitation cross section (and rate) is found to be the dominant followed by the j = 0 -> j(') = 2 in these collision energies. The close-coupling, coupled-state, and infinite-order sudden approximations coupling calculations have been performed in the energy range of 0.1-1.0 eV using vibrational ground potential. The rotational cross sections have been obtained by performing computationally accurate close-coupling calculations at 0.1 eV using vibrationally averaged potential (nu = 1) and compared with the results of vibrational ground potential. PMID- 22299882 TI - A laser-induced fluorescence study of the jet-cooled nitrous oxide cation (N2O+). AB - Laser-induced fluorescence and wavelength resolved emission spectra of the A (2)Sigma(+) - X (2)Pi(i) electronic transition of the jet-cooled nitrous oxide cation have been recorded. The ions were produced in a pulsed electric discharge at the exit of a supersonic expansion using a precursor mixture of N(2)O in high pressure argon. Both spin-orbit components of the 0(0) (0) band were studied at high resolution and rotationally analyzed to provide precise molecular constants for the combining states. Emission spectra were obtained by laser excitation of the 0(0) (0), 2(0) (1), 3(0) (1), and 2(0) (2) absorption bands, providing extensive data on the ground state bending, stretching, and combination vibrational levels. These data were fitted to a Renner-Teller model including spin-orbit, anharmonic, and Fermi resonance terms. The observed energy levels and fitted parameters were found to be comparable to those in the literature predicted from an ab initio potential energy surface. PMID- 22299883 TI - Infrared absorption by collisional H2-He complexes at temperatures up to 9000 K and frequencies from 0 to 20,000 cm(-1). AB - Quantum chemical methods have been used elsewhere to obtain the potential energy surface (PES) and the induced dipole surface (IDS) of H(2)-He collisional complexes at eight different H-H bond distances, fifteen atom-molecule separations, and 19 angular orientations each [X. Li, A. Mandal, E. Miliordos, and K. L. C. Hunt, J. Chem. Phys. 136, 044320 (2012)]. An atom-molecule state-to state scattering formalism is employed, which couples the collisional molecular complex to the electromagnetic radiation field. In this way, we obtain theoretical collision-induced absorption (CIA) spectra of H(2)-He complexes for frequencies from 0 to 20,000 cm(-1) and temperatures up to 9000 K. The work is based on the fundamental theory and is motivated by current research of certain astronomical objects, such as cool white dwarf stars, cool main sequence stars, M dwarfs, exoplanets, so-called "first" stars. We compare our theoretical results to existing laboratory measurements of CIA spectra; very close agreement of theory and measurement is observed. We also discuss similar previous theoretical efforts. PMID- 22299884 TI - Interaction-induced dipoles of hydrogen molecules colliding with helium atoms: a new ab initio dipole surface for high-temperature applications. AB - We report new ab initio results for the interaction-induced dipole moments DeltaMU of hydrogen molecules colliding with helium atoms. These results are needed in order to calculate collision-induced absorption spectra at high temperatures; applications include modeling the radiative profiles of very cool white dwarf stars, with temperatures from 3500 K to 9000 K. We have evaluated the dipoles based on finite-field calculations, with coupled cluster methods in MOLPRO 2006 and aug-cc-pV5Z (spdfg) basis sets for both the H and He centers. We have obtained values of DeltaMU for eight H(2) bond lengths ranging from 0.942 a.u. to 2.801 a.u., for 15 intermolecular separations R ranging from 2.0 a.u. to 10.0 a.u., and for 19 different relative orientations. In general, our values agree well with earlier ab initio results, for the geometrical configurations that are treated in common, but we have determined more points on the collision induced dipole surface by an order of magnitude. These results make it possible to calculate transition probabilities for molecules in excited vibrational states, overtones, and rotational transitions with DeltaJ > 4. We have cast our results in the symmetry-adapted form needed for absorption line shape calculations, by expressing DeltaMU as a series in the spherical harmonics of the orientation angles of the intermolecular vector and of a unit vector along the H(2) bond axis. The expansion coefficients depend on the H(2) bond length and the intermolecular distance R. For large separations R, we show that the ab initio values of the leading coefficients converge to the predictions from perturbation theory, including both classical multipole polarization and dispersion effects. PMID- 22299885 TI - Mechanisms for thermal conduction in hydrogen hydrate. AB - Extensive equilibrium molecular dynamics simulations have been performed to investigate thermal conduction mechanisms via the Green-Kubo approach for (type II) hydrogen hydrate, at 0.05 kbar and between 30 and 250 K, for both lightly filled H(2) hydrates (1s4l) and for more densely filled H(2) systems (2s4l), in which four H(2) molecules are present in the large cavities, with respective single- and double-occupation of the small cages. The TIP4P water model was used in conjunction with a fully atomistic hydrogen potential along with long-range Ewald electrostatics. It was found that substantially less damping in guest-host energy transfer is present in hydrogen hydrate as is observed in common type I clathrates (e.g., methane hydrate), but more akin in to previous results for type II and H methane hydrate polymorphs. This gives rise to larger thermal conductivities relative to common type I hydrates, and also larger than type II and H methane hydrate polymorphs, and a more crystal-like temperature dependence of the thermal conductivity. PMID- 22299886 TI - Fragility of supercooled liquids from differential scanning calorimetry traces: theory and experiment. AB - Starting from the Debye model for frequency-dependent specific heat and the Vogel Fulcher-Tammann (VFT) model for its relaxation time, an analytic expression is presented for the heat capacity versus temperature trace for differential scanning calorimetry (DSC) of glass transitions, suggesting a novel definition of the glass transition temperature based on a dimensionless criterion. An explicit expression is presented for the transition temperature as a function of the VFT parameters and the cooling rate, and for the slope as a function of fragility. Also a generalization of the results to non-VFT and non-Debye relaxation is given. Two unique ways are proposed to tackle the inverse problem, i.e., to extract the fragility from an experimental DSC trace. Good agreement is found between theoretically predicted DSC traces and experimental DSC traces for glycerol for different cooling rates. PMID- 22299887 TI - Long-range orientation correlation in liquids. AB - Strong short-range intermolecular interactions result in position and orientation correlations between nearest neighbour molecules in isotropic liquids, and it is generally assumed that such correlations extend at most a few molecular diameters. This assumption is contradicted by results from second harmonic light scattering experiments presented here, which reveal long-range orientation correlations in several isotropic liquids including water. These experiments measure the polarization dependence of the scattered light, and the observations are interpreted in terms of transverse and longitudinal polar collective modes, as well as simple explicit models. The results revise our understanding of the structure of molecular liquids and provide a test of computational simulations. PMID- 22299888 TI - Model-free nuclear magnetic resonance study of intermolecular free energy landscapes in liquids with paramagnetic Ln3+ spotlights: theory and application to Arg-Gly-Asp. AB - We propose an easily applicable method for investigating the pair distribution function of a lanthanide Ln(3+) complex LnL (L = ligand) with respect to any solvent or solute molecule A carrying observable nuclear spins. Let r be the distance of Ln(3+) to the observed nuclear spin I. We derive a simple expression of the experimental value of the configurational average of 1/r(6) in terms of longitudinal paramagnetic relaxation (rate) enhancements (PREs) of the spin I measured on a standard high-resolution NMR spectrometer and due to well-chosen concentrations of LnL complexes in which Ln(3+) is a fast-relaxing paramagnetic lanthanide or the slowly-relaxing gadolinium Gd(3+). The derivation is justified in the general case of a molecule A which is by turns in a bound state where it follows the complex and a free state where it moves independently. It rests on the expression of the underlying PRE theory in terms of the angle-dependent pair distribution function of LnL and A. The simplifications of this theory in the high-field regime and under the condition of fast exchange between bound and free states are carefully discussed. We also show that original information on the angle dependence of the molecular pair distribution function can be gained from the measured paramagnetic dipolar shifts induced by complexed fast-relaxing Ln(3+) ions. The method is illustrated by the case study of the anionic Lnttha(3 ) = [Ln(3+)(ttha)](3-) (ttha(6-) = triethylene tetraamine hexacetate) complex interacting with the biologically important tripeptide Arg-Gly-Asp (RGD) which carries peripheral ionic groups. The usefulness of an auxiliary reference outer sphere probe solute is emphasized. PMID- 22299889 TI - Free-energy analysis of the electron-density fluctuation in the quantum mechanical/molecular-mechanical simulation combined with the theory of energy representation. AB - The relationship is investigated for QM/MM (quantum-mechanical/molecular mechanical) systems between the fluctuations of the electronic state of the QM subsystem and of the solvation effect due to the QM-MM interaction. The free energy change due to the electron-density fluctuation around its average is highlighted, and is evaluated through an approximate functional formulated in terms of distribution functions of the many-body coupling (pairwise non-additive) part of the QM-MM interaction energy. A set of QM/MM simulations are conducted in MM water solvent for QM water solute in ambient and supercritical conditions and for QM glycine solute in the neutral and zwitterionic forms. The variation of the electronic distortion energy of the QM solute in the course of QM/MM simulation is then shown to be compensated by the corresponding variation of the free energy of solvation. The solvation free energy conditioned by the electronic distortion energy is further analyzed with its components. It is found that the many-body contribution is essentially equal between the free energy and the average sum of solute-solvent interaction energy. PMID- 22299890 TI - Dynamical cage behaviour and hydrogen migration in hydrogen and hydrogen tetrahydrofuran clathrate hydrates. AB - Classical equilibrium molecular dynamics simulations have been performed to investigate dynamical properties of cage radial breathing modes and intra- and inter-cage hydrogen migration in both pure hydrogen and mixed hydrogen tetrahydrofuran sII hydrates at 0.05 kbar and up to 250 K. For the mixed H(2)-THF system in which there is single H(2) occupation of the small cage (labelled "1SC 1LC"), we find that no H(2) migration occurs, and this is also the case for pure H(2) hydrate with single small-cavity occupation and quadruple occupancy for large cages (dubbed "1SC 4LC"). However, for the more densely filled H(2)-THF and pure-H(2) systems, in which there is double H(2) occupation in the small cage (dubbed "2SC 1LC" and "2SC 4LC," respectively), there is an onset of inter-cage H(2) migration events from the small cages to neighbouring cavities at around 200 K, with an approximate Arrhenius temperature-dependence for the migration rate from 200 to 250 K. It was found that these "cage hopping" events are facilitated by temporary openings of pentagonal small-cage faces with the relaxation and reformation of key stabilising hydrogen bonds during and following passage. The cages remain essentially intact up to 250 K, save for transient hydrogen bond weakening and reformation during and after inter-cage hydrogen diffusion events in the 200-250 K range. The "breathing modes," or underlying frequencies governing the variation in the cavities' radii, exhibit a certain overlap with THF rattling motion in the case of large cavities, while there is some overlap of small cages' radial breathing modes with lattice acoustic modes. PMID- 22299891 TI - Transport coefficients of the TIP4P-2005 water model. AB - A detailed understanding of the dynamics of liquid water at molecular level is of fundamental importance as well as have applications in many branches of science and technology. In this work, the diffusion of the TIP4P-2005 model of water is systematically investigated in liquid phase in the temperature range 210-310 K. The translational and rotational diffusions, as well as correlations between them, are examined. The effects of system size and shape are also probed in this study. The results suggest the presence of a temperature of dynamical arrest of molecular translations in the range of 150-180 K and of molecular rotations in the range of 80-130 K, depending on specific direction. A substantial change in the preferred directions of translations and rotations relative to the molecular coordinate system is observed slightly below (~15 K) the melting temperature of the model. It is shown that there is a correlation between translational and rotational molecular motions essential for diffusion in the liquid. The presence of hydrodynamic size effects is confirmed and quantified; it is also shown that using a non-cubic simulation box for a liquid system leads to an anisotropic splitting in the diffusion tensor. The findings of this study enhance our general understanding of models of water, specifically the TIP4P-2005 model, as well as provide evidences of the direct connection between thermodynamics of liquid water and dynamics of its molecules. PMID- 22299892 TI - Molecular vibrations of methane molecules in the structure I clathrate hydrate from ab initio molecular dynamics simulation. AB - Vibrational frequencies of guest molecules in clathrate hydrates reflect the molecular environment and dynamical behavior of molecules. A detailed understanding of the mechanism for the vibrational frequency changes of the guest molecules in the clathrate hydrate cages is still incomplete. In this study, molecular vibrations of methane molecules in a structure I clathrate hydrate are calculated from ab initio molecular dynamics simulation. The vibrational spectra of methane are computed by Fourier transform of autocorrelation functions, which reveal distinct separation of each vibrational mode. Calculated symmetric and asymmetric stretching vibrational frequencies of methane molecules are lower in the large cages than in the small cages (8 and 16 cm(-1) for symmetric and asymmetric stretching, respectively). These changes are closely linked with the C H bond length. The vibrational frequencies for the bending and rocking vibrational modes nearly overlap in each of the cages. PMID- 22299893 TI - Modeling the hydration of mono-atomic anions from the gas phase to the bulk phase: the case of the halide ions F-, Cl-, and Br-. AB - In this work, we investigate the hydration of the halide ions fluoride, chloride, and bromide using classical molecular dynamics simulations at the 10 ns scale and based on a polarizable force-field approach, which treats explicitly the cooperative bond character of strong hydrogen bond networks. We have carried out a thorough analysis of the ab initio data at the MP2 or CCSD(T) level concerning anion/water clusters in gas phase to adjust the force-field parameters. In particular, we consider the anion static polarizabilities computed in gas phase using large atomic basis sets including additional diffuse functions. The information extracted from trajectories in solution shows well structured first hydration shells formed of 6.7, 7.0, and 7.6 water molecules at about 2.78 A, 3.15 A, and 3.36 A for fluoride, chloride, and bromide, respectively. These results are in excellent agreement with the latest neutron- and x-ray diffraction studies. In addition, our model reproduces several other properties of halide ions in solution, such as diffusion coefficients, description of hydration processes, and exchange reactions. Moreover, it is also able to reproduce the electrostatic properties of the anions in solution (in terms of anion dipole moment) as reported by recent ab initio quantum simulations. All the results show the ability of the proposed model in predicting data, as well as the need of accounting explicitly for the cooperative character of strong hydrogen bonds to reproduce ab initio potential energy surfaces in a mean square sense and to build up a reliable force field. PMID- 22299894 TI - Surface structure and phase transition of K adsorption on Au(111): by ab initio atomistic thermodynamics. AB - We studied the interactions between atomic potassium (K) and Au(111) at a range of coverage (i.e., Theta(K) = 0.11-0.5 monolayer (ML)) by ab initio atomic thermodynamics. For K on-surface adsorption, we found that K energetically favors the three-fold hollow sites (fcc or hcp), while the most significant surface rumpling was obtained at the atop sites. The incorporation of gold atoms in the adsorbate layer gradually becomes energetically favorable with increasing K coverage. We proposed a possible model with a stoichiometry of K(2)Au for the (2 * 2)-0.5 ML phase observed in lower energy electron diffraction (LEED): one K at atop site and the other K as well as one Au adatom at the second-nearest fcc/hcp and hcp/fcc, respectively. Clear theoretical evidences were given for the ionic interaction of K on Au surface. Additionally, phase transitions were predicted based on chemical potential equilibrium of K, largely in line with the earlier reported LEED observations: the clean surface -> (?3 * ?3)R30 degrees -> (2 * 2), and (2 * 2) -> (?3 * ?3)R30 degrees reversely at an elevated temperature. PMID- 22299895 TI - Modeling simple amphiphilic solutes in a Jagla solvent. AB - Methanol is an amphiphilic solute whose aqueous solutions exhibit distinctive physical properties. The volume change upon mixing, for example, is negative across the entire composition range, indicating strong association. We explore the corresponding behavior of a Jagla solvent, which has been previously shown to exhibit many of the anomalous properties of water. We consider two models of an amphiphilic solute: (i) a "dimer" model, which consists of one hydrophobic hard sphere linked to a Jagla particle with a permanent bond, and (ii) a "monomer" model, which is a limiting case of the dimer, formed by concentrically overlapping a hard sphere and a Jagla particle. Using discrete molecular dynamics, we calculate the thermodynamic properties of the resulting solutions. We systematically vary the set of parameters of the dimer and monomer models and find that one can readily reproduce the experimental behavior of the excess volume of the methanol-water system as a function of methanol volume fraction. We compare the pressure and temperature dependence of the excess volume and the excess enthalpy of both models with experimental data on methanol-water solutions and find qualitative agreement in most cases. We also investigate the solute effect on the temperature of maximum density and find that the effect of concentration is orders of magnitude stronger than measured experimentally. PMID- 22299896 TI - Potential of mean force between hydrophobic solutes in the Jagla model of water and implications for cold denaturation of proteins. AB - Using the Jagla model potential we calculate the potential of mean force (PMF) between hard sphere solutes immersed in a liquid displaying water-like properties. Consistent estimates of the PMF are obtained by (a) umbrella sampling, (b) calculating the work done by the mean force acting on the hard spheres as a function of their separation, and (c) determining the position dependent chemical potential after calculating the void space in the liquid. We calculate the PMF for an isobar along which cold denaturation of a model protein has previously been reported. We find that the PMF at contact varies non monotonically, which is consistent with the observed cold denaturation. The Henry constant also varies non-monotonically with temperature. We find, on the other hand, that a second (solvent separated) minimum of the PMF becomes deeper as temperature decreases. We calculate the solvent-solvent pair correlation functions for solvents near the solute and in the bulk, and show that, as temperature decreases, the two pair correlation functions become indistinguishable, suggesting that the perturbation of solvent structure by the solute diminishes as temperature decreases. The solvent-solute pair correlation function at contact grows as the temperature decreases. We calculate the cavity correlation function and show the development of a solvent-separated peak upon decrease of temperature. These observations together suggest that cold denaturation occurs when the solvent penetrates between hydrophobic solutes in configurations with favorable free energy. Our results thus suggest that cold denatured proteins are structured and that cold denaturation arises from strong solvent-solute interactions, rather than from entropic considerations as in heat denaturation. PMID- 22299897 TI - Reorientation dynamics of nanoconfined water: power-law decay, hydrogen-bond jumps, and test of a two-state model. AB - The reorientation dynamics of water confined within nanoscale, hydrophilic silica pores are investigated using molecular dynamics simulations. The effect of surface hydrogen-bonding and electrostatic interactions are examined by comparing with both a silica pore with no charges (representing hydrophobic confinement) and bulk water. The OH reorientation in water is found to slow significantly in hydrophilic confinement compared to bulk water, and is well-described by a power law decay extending beyond one nanosecond. In contrast, the dynamics of water in the hydrophobic pore are more modestly affected. A two-state model, commonly used to interpret confined liquid properties, is tested by analysis of the position dependence of the water dynamics. While the two-state model provides a good fit of the orientational decay, our molecular-level analysis evidences that it relies on an over-simplified picture of water dynamics. In contrast with the two-state model assumptions, the interface dynamics is markedly heterogeneous, especially in the hydrophilic pore and there is no single interfacial state with a common dynamics. PMID- 22299898 TI - Monte Carlo predictions of phase equilibria and structure for dimethyl ether + sulfur dioxide and dimethyl ether + carbon dioxide. AB - A new force field for dimethyl ether (DME) based on the Lennard-Jones (LJ) 12-6 plus point charge functional form is presented in this work. This force field reproduces experimental saturated liquid and vapor densities, vapor pressures, heats of vaporization, and critical properties to within the statistical uncertainty of the combined experimental and simulation measurements for temperatures between the normal boiling and critical point. Critical parameters and normal boiling point are predicted to within 0.1% of experiment. This force field is used in grand canonical histogram reweighting Monte Carlo simulations to predict the pressure composition diagrams for the binary mixtures DME + SO(2) at 363.15 K and DME + CO(2) at 335.15 and 308.15 K. For the DME + SO(2) mixture, simulation is able to qualitatively reproduce the minimum pressure azeotropy observed experimentally for this mixture, but quantitative errors exist, suggesting that multibody effects may be important in this system. For the DME + CO(2) mixture, simulation is able to predict the pressure-composition behavior within 1% of experimental data. Simulations in the isobaric-isothermal ensemble are used to determine the microstructure of DME + SO(2) and DME + CO(2) mixtures. The DME + SO(2) shows weak pairing between DME and SO(2) molecules, while no specific pairing or aggregation is observed for mixtures of DME + CO(2). PMID- 22299899 TI - Influence of monovalent ions on density fluctuations in hydrothermal aqueous solutions by small angle X-ray scattering. AB - Synchrotron small angle X-ray scattering measurements on water and alkaline bromine aqueous solutions (XBr, with X = Li, Rb, or Cs) were carried out from ambient to supercritical conditions. The temperature was increased from 300 to 750 K along several isobars between 24 and 35 MPa. The correlation length and the structure factor were extracted from the data following the Ornstein-Zernike formalism. We obtained experimental evidence of the shift of the critical point and isochore and their dependence on the ions concentration (0.33 mol/kg and 1.0 mol/kg). We also observed that the size of the density fluctuations and the structure factor increase with the presence of the ions and that this effect is positively correlated with the atomic number of the cation. These behaviors were compared with ZnBr(2) and NaCl systems from the literature. PMID- 22299900 TI - Initial chemical events in shocked octahydro-1,3,5,7-tetranitro-1,3,5,7- tetrazocine: a new initiation decomposition mechanism. AB - We have performed ab initio molecular dynamics simulations in conjunction with the multiscale shock technique to study the initial chemical processes of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) under shock wave loading. The results show that the initial decomposition of shocked HMX is triggered by the N-O bond breaking and the ring opening. This will initiate many decomposition reactions and lead to the production of many small radicals at a moment. As the shock compression continues, these small radicals recombine to produce many large radicals and further form ring-shaped radicals. Then, these radicals begin to further decompose. It is also found that the system transiently produces a large number of metallic states under the shock compression. Our simulations thus suggest a new mechanism for the initial chemical processes of shocked HMX and provide fundamental insight into the initial mechanism at the atomistic level, which is of important implication for understanding and development of energetic materials. PMID- 22299901 TI - Polarization dependent resonant x-ray emission spectroscopy of D2O and H2O water: assignment of the local molecular orbital symmetry. AB - The polarization dependence of the split two peaks in the lone-pair region in the x-ray emission spectra has been determined at several different excitation energies for both D(2)O and H(2)O water. In contrast to predictions based on a narrow range of local water structures where the two peaks would be of different molecular orbital symmetry and arise from, respectively, intact and dissociated molecules, we show that the two peaks in the lone-pair region are both of lone pair 1b(1) orbital symmetry. The results support the interpretation that the two peaks appear due to fluctuations between two distinct different main structural environments. PMID- 22299902 TI - Size effects in reactive circular site interactions. AB - The complete series solution for the reactant diffusion and reaction at two diffusion-controlled chemically reactive surface sites of radii a(1) and a(2), located in an inert plane an arbitrary center-to-center distance d apart, is presented. Rigorous, analytical forms are developed to calculate the site reaction rates in terms of the dimensionless intersite distance sigma[=d/(a(1) + a(2))] and the site radius ratio gamma(=a(1)//a(2)). Numerical simulation and approximate theoretical results from the recent literature are compared to the exact site reaction rates. While general agreement was noted over the ranges of gamma and sigma, significant errors in the Wilemski-Fixman-Weiss site rates were found at small gamma and sigma < 3. PMID- 22299903 TI - Ab initio derivation of multi-orbital extended Hubbard model for molecular crystals. AB - From configuration interaction (CI) ab initio calculations, we derive an effective two-orbital extended Hubbard model based on the gerade (g) and ungerade (u) molecular orbitals (MOs) of the charge-transfer molecular conductor (TTM TTP)I(3) and the single-component molecular conductor [Au(tmdt)(2)]. First, by focusing on the isolated molecule, we determine the parameters for the model Hamiltonian so as to reproduce the CI Hamiltonian matrix. Next, we extend the analysis to two neighboring molecule pairs in the crystal and we perform similar calculations to evaluate the inter-molecular interactions. From the resulting tight-binding parameters, we analyze the band structure to confirm that two bands overlap and mix in together, supporting the multi-band feature. Furthermore, using a fragment decomposition, we derive the effective model based on the fragment MOs and show that the staking TTM-TTP molecules can be described by the zig-zag two-leg ladder with the inter-molecular transfer integral being larger than the intra-fragment transfer integral within the molecule. The inter-site interactions between the fragments follow a Coulomb law, supporting the fragment decomposition strategy. PMID- 22299904 TI - Transport properties of the rough hard sphere fluid. AB - Results are presented of a systematic study of the transport properties of the rough hard sphere fluid. The rough hard sphere fluid is a simple model consisting of spherical particles that exchange linear and angular momenta, and energy upon collision. This allows a study of the sole effect of particle rotation upon fluid properties. Molecular dynamics simulations have been used to conduct extensive benchmark calculations of self-diffusion, shear and bulk viscosity, and thermal conductivity coefficients. As well, the validity of several kinetic theory equations have been examined at various levels of approximation as a function of density and translational-rotational coupling. In particular, expressions from Enskog theory using different numbers of basis sets in the representation of the distribution function were tested. Generally Enskog theory performs well at low density but deviates at larger densities, as expected. The dependence of these expressions upon translational-rotational coupling was also examined. Interestingly, even at low densities, the agreement with simulation results was sometimes not even qualitatively correct. Compared with smooth hard sphere behaviour, the transport coefficients can change significantly due to translational-rotational coupling and this effect becomes stronger the greater the coupling. Overall, the rough hard sphere fluid provides an excellent model for understanding the effects of translational-rotational coupling upon transport coefficients. PMID- 22299905 TI - Solution-phase photochemistry of a [FeFe]hydrogenase model compound: evidence of photoinduced isomerisation. AB - The solution-phase photochemistry of the [FeFe] hydrogenase subsite model (MU S(CH(2))(3)S)Fe(2)(CO)(4)(PMe(3))(2) has been studied using ultrafast time resolved infrared spectroscopy supported by density functional theory calculations. In three different solvents, n-heptane, methanol, and acetonitrile, relaxation of the tricarbonyl intermediate formed by UV photolysis of a carbonyl ligand leads to geminate recombination with a bias towards a thermodynamically less stable isomeric form, suggesting that facile interconversion of the ligand groups at the Fe center is possible in the unsaturated species. In a polar or hydrogen bonding solvent, this process competes with solvent substitution leading to the formation of stable solvent adduct species. The data provide further insight into the effect of incorporating non-carbonyl ligands on the dynamics and photochemistry of hydrogenase-derived biomimetic compounds. PMID- 22299906 TI - High energy transmission of Al2O3 doped with light transition metals. AB - The transmission of transparent colored ceramics based on Al(2)O(3) doped with light transition metals is measured in the visible and infrared range. To clarify the role of the dopands we perform ab initio calculations. We discuss the electronic structure and present optical spectra obtained in the independent particle approximation. We argue that the gross spectral features of Co- and Ni doped Al(2)O(3) samples are described by our model, while the validity of the approach is limited for Cr-doped Al(2)O(3). PMID- 22299907 TI - Melting and superheating of sI methane hydrate: molecular dynamics study. AB - Melting and decay of the superheated sI methane structure are studied using molecular dynamics simulation. The melting curve is calculated by the direct coexistence simulations in a wide range of pressures up to 5000 bar for the SPC/E, TIP4P/2005 and TIP4P/Ice water models and the united-atom model for methane. We locate the kinetic stability boundary of the superheated metastable sI structure that is found to be surprisingly high comparing with the predictions based on the classical nucleation theory. PMID- 22299908 TI - A note on the nucleation with multiple steps: parallel and series nucleation. AB - Parallel and series nucleation are the basic elements of the complex nucleation process when two saddle points exist on the free-energy landscape. It is pointed out that the nucleation rates follow formulas similar to those of parallel and series connection of resistors or conductors in an electric circuit. Necessary formulas to calculate individual nucleation rates at the saddle points and the total nucleation rate are summarized, and the extension to the more complex nucleation process is suggested. PMID- 22299909 TI - On the influence of a patterned substrate on crystallization in suspensions of hard spheres. AB - We present a computer simulation study on crystal nucleation and growth in supersaturated suspensions of mono-disperse hard spheres induced by a triangular lattice substrate. The main result is that compressed substrates are wet by the crystalline phase (the crystalline phase directly appears without any induction time), while for stretched substrates we observe heterogeneous nucleation. The shapes of the nucleated crystallites fluctuate strongly. In the case of homogeneous nucleation amorphous precursors have been observed [T. Schilling et al., Phys. Rev. Lett. 105(2), 025701 (2010)]. For heterogeneous nucleation we do not find such precursors. The fluid is directly transformed into highly ordered crystallites. PMID- 22299910 TI - Stabilization and growth of non-native nanocrystals at low and atmospheric pressures. AB - The stabilization and growth of nanocrystals in "non-native" structures is explored via density functional calculations. Non-native and "native" bulk structures differ in their discrete translational symmetry. Computations suggest that the lower surface energy of the non-native structures always facilitates their stabilization in the early stages of crystal growth. In the compound semiconductors considered here, the transition pathways between non-native and native structures involve planar or near-planar depolarized layers and the growth conditions have significant effects on the stabilization and growth of non-native structures. The findings of this study help in identifying heuristics for the synthesis of non-native nanocrystals. PMID- 22299911 TI - Epitaxial oxide bilayer on Pt (001) nanofacets. AB - We observed an epitaxial, air-stable, partially registered (2 * 1) oxide bilayer on Pt (001) nanofacets [V. Komanicky, A. Menzel, K.-C. Chang, and H. You, J. Phys. Chem. 109, 23543 (2005)]. The bilayer is made of two half Pt layers; the top layer has four oxygen bonds and the second layer two. The positions and oxidation states of the Pt atoms are determined by analyzing crystal truncation rods and resonance scattering data. The positions of oxygen atoms are determined by density functional theory (DFT) calculations. Partial registry on the nanofacets and the absence of such registry on the extended Pt (001) surface prepared similarly are explained in DFT calculations by strain relief that can be accommodated only by nanoscale facets. PMID- 22299912 TI - Growth of a Pt film on non-reduced ceria: a density functional theory study. AB - The growth of platinum on non-reduced CeO(2) (111) surface is studied by means of calculations based on the density functional theory. Particles of increasing size are formed on the oxide surface by incorporating the platinum atoms one by one until multilayer films are obtained. The main conclusion is that platinum atoms tend to maximize the number of metallic bonds and to approach the situation of the bulk, hence preferring films to particles, particles to isolated atoms, and a three-dimensional growth to a two-dimensional one. The supported particles and the films exhibit a contraction of the Pt-Pt distances, with respect to those of the Pt bulk, in order to match the ceria lattice. The density of states projected on the film surface platinum atoms shows important differences in shape and energy (lower d-band center) compared to the Pt(111) reference surface, which could be the major reason for the observed changes in catalytic reactivity when deposited particles are compared with single crystal surfaces. PMID- 22299913 TI - Modifying thermal transport in electrically conducting polymers: effects of stretching and combining polymer chains. AB - If their thermal conductivity can be lowered, polyacetylene (PA) and polyaniline (PANI) offer examples of electrically conducting polymers that can have potential use as thermoelectrics. Thermal transport in such polymers is primarily influenced by bonded interactions and chain orientations relative to the direction of heat transfer. We employ molecular dynamics simulations to investigate two mechanisms to control the phonon thermal transport in PANI and PA, namely, (1) mechanical strain and (2) polymer combinations. The molecular configurations of PA and PANI have a significant influence on their thermal transport characteristics. The axial thermal conductivity increases when a polymer is axially stretched but decreases under transverse tension. Since the strain dependence of the thermal conductivity is related to the phonon scattering among neighboring polymer chains, this behavior is examined through Herman's orientation factor that quantifies the degree of chain alignment in a given direction. The conductivity is enhanced as adjacent chains become more aligned along the direction of heat conduction but diminishes when they are orthogonally oriented to it. Physically combining these polymers reduces the thermal conductivity, which reaches a minimum value for a 2:3 PANI/PA chain ratio. PMID- 22299914 TI - Dynamics of solvent-free grafted nanoparticles. AB - The diffusivity and structural relaxation characteristics of oligomer-grafted nanoparticles have been investigated with simulations of a previously proposed coarse-grained model at atmospheric pressure. Solvent-free, polymer-grafted nanoparticles as well as grafted nanoparticles in a melt were compared to a reference system of bare (ungrafted) particles in a melt. Whereas longer chains lead to a larger hydrodynamic radius and lower relative diffusivity for grafted particles in a melt, bulk solvent-free nanoparticles with longer chains have higher relative diffusivities than their short chain counterparts. Solvent-free nanoparticles with short chains undergo a glass transition as indicated by a vanishing diffusivity, diverging structural relaxation time and the formation of body-centered-cubic-like order. Nanoparticles with longer chains exhibit a more gradual increase in the structural relaxation time with decreasing temperature and concomitantly increasing particle volume fraction. The diffusivity of the long chain nanoparticles exhibits a minimum at an intermediate temperature and volume fraction where the polymer brushes of neighboring particles overlap, but must stretch to fill the interparticle space. PMID- 22299915 TI - A new numerical approach to dense polymer brushes and surface instabilities. AB - We present a numerical self-consistent field (SCF) method which describes freely jointed chains of spherical monomers applied to densely grafted polymer brushes. We discuss both the Flory-Huggins model and the Carnahan-Starling equation of state and show the latter being preferable within our model at polymer volume fractions above 10%. We compare the results of our numerical method with data from molecular dynamics (MD) simulations [G.-L. He, H. Merlitz, J.-U. Sommer, and C.-X. Wu, Macromolecules 40, 6721 (2007)] and analytical SCF calculations [P. M. Biesheuvel, W. M. de Vos, and V. M. Amoskov, Macromolecules 41, 6254 (2008)] and obtain close agreement between the density profiles up to high grafting densities. In contrast to prior numerical and analytical studies of densely grafted polymer brushes our method provides detailed information about chain configurations including fluctuation, depletion, and packing effects. Using our model we could study the recently discovered instability of densely grafted polymer brushes with respect to slight variations of individual chain lengths, driven by fluctuation effects [H. Merlitz, G.-L. He, C.-X. Wu, and J.-U. Sommer, Macromolecules 41, 5070 (2008)]. The obtained results are in very close agreement with corresponding MD simulations. PMID- 22299916 TI - Dynamics of fibers in a wide microchannel. AB - Dynamics of single flexible non-Brownian fibers, tumbling in a Poiseuille flow between two parallel solid plane walls, is studied with the use of the HYDROMULTIPOLE numerical code, based on the multipole expansion of the Stokes equations, corrected for lubrication. Fibers, which are closer to a wall, more flexible (less stiff) or longer, deform more significantly and, for a wide range of the system parameters, they faster migrate towards the middle plane of the channel. For the considered systems, fiber velocity along the flow is only slightly smaller than (and can be well approximated by) the Poseuille flow velocity at the same position. In this way, the history of a fiber migration across the channel is sufficient to determine with a high accuracy its displacement along the flow. PMID- 22299917 TI - Effects of static and temporally fluctuating tensions on semiflexible polymer looping. AB - Biopolymer looping is a dynamic process that occurs ubiquitously in cells for gene regulation, protein folding, etc. In cellular environments, biopolymers are often subject to tensions which are either static or temporally fluctuating far away from equilibrium. We study the dynamics of semiflexible polymer looping in the presence of such tensions by using Brownian dynamics simulation combined with an analytical theory. We show a minute tension dramatically changes the looping time, especially for long chains. Considering a dichotomically flipping noise as a simple example of the nonequilibrium tension, we find the phenomenon of resonant activation, where the looping time can be the minimum at an optimal flipping time. We discuss our results in connection with recent experiments. PMID- 22299919 TI - Note: percolation in two-dimensional flexible chains systems. PMID- 22299918 TI - Consequences of local inter-strand dehybridization for large-amplitude bending fluctuations of double-stranded DNA. AB - The wormlike chain model of DNA bending accurately reproduces single-molecule force-extension profiles of long (kilobase) chains. These bending statistics over large scales do not, however, establish a unique microscopic model for elasticity at the 1-10 basepair (bp) scale, which holds particular interest in biological contexts. Here, we examine a class of microscopic models which allow for disruption of base pairing (i.e., a "melt" or "kink", generically an "excitation") and consequently enhanced local flexibility. We first analyze the effect on the excitation free energy of integrating out the spatial degrees of freedom in a wormlike chain. Based on this analysis, we present a formulation of these models that ensures consistency with the well-established thermodynamics of melting in long chains. Using a new method to calculate cyclization statistics of short chains from enhanced-sampling Monte Carlo simulations, we compute J-factors of a meltable wormlike chain over a broad range of chain lengths, including very short molecules (30 bp) that have not yet been explored experimentally. For chains longer than about 120 bp, including most molecules studied to date in the laboratory, we find that melting excitations have little impact on cyclization kinetics. Strong signatures of melting, which might be resolved within typical experimental scatter, emerge only for shorter chains. PMID- 22299920 TI - Comment on "Structure and thermodynamics of hard-core Yukawa fluids: thermodynamic perturbation approaches" [J. Chem. Phys, 135, 034505 (2011)]. AB - We would like to show that what has been presented in the paper by Kim, Kim, and Seong [J. Chem. Phys, 135, 034505 (2011)] is nothing but an unnecessarily complicated version of (optimized) random phase approximation. PMID- 22299922 TI - Invited Article: Refractive index matched scanning of dense granular materials. AB - We review an experimental method that allows to probe the time-dependent structure of fully three-dimensional densely packed granular materials and suspensions by means of particle recognition. The method relies on submersing a granular medium in a refractive index matched fluid. This makes the resulting suspension transparent. The granular medium is then visualized by exciting, layer by layer, the fluorescent dye in the fluid phase. We collect references and unreported experimental know-how to provide a solid background for future development of the technique, both for new and experienced users. PMID- 22299923 TI - Measurement of phase retardation of waveplate online based on laser feedback. AB - Polarization flipping accompanying with intensity transfer between two eigenstates of one laser mode happens when waveplate is placed in external cavity. The position of polarization flipping of two eigenstates is a function of phase retardation of waveplate. Phase retardation of waveplate is measured through analyzing the position of polarization flipping of two eigenstates. The measurement accuracy of phase retardation is 0.22 degrees . A new structure of optical cement tray which can eliminate stress birefringence from optical cement process is invented. The accuracy of waveplate manufacture can be improved greatly based on the work of this article. PMID- 22299924 TI - High-precision laser-assisted absolute determination of x-ray diffraction angles. AB - A novel technique for absolute wavelength determination in high-precision crystal x-ray spectroscopy recently introduced has been upgraded reaching unprecedented accuracies. The method combines visible laser beams with the Bond method, where Bragg angles (theta and -theta) are determined without any x-ray reference lines. Using flat crystals this technique makes absolute x-ray wavelength measurements feasible even at low x-ray fluxes. The upgraded spectrometer has been used in combination with first experiments on the 1s2p(1)P(1) -> 1s(2)(1)S(0) w-line in He-like argon. By resolving a minute curvature of the x-ray lines the accuracy reaches there the best ever reported value of 1.5 ppm. The result is sensitive to predicted second-order QED contributions at the level of two-electron screening and two-photon radiative diagrams and will allow for the first time to benchmark predicted binding energies for He-like ions at this level of precision. PMID- 22299925 TI - Fast magneto-optical spectrometry by spectrometer. AB - Time efficient measurement of the spectroscopic magneto-optical (MO) activity of materials has always been desirable. In conventional MO systems, the monochromator produces quasi-monochromatic light in a narrow wavelength window. Therefore, to measure the spectroscopic MO activity, a large number of measurements over the full spectra is required to obtain satisfactory wavelength resolution and thus is very time consuming. Here, we develop a novel system that is capable of fast measurement of the MO activity by only one white light source, two polarizers, one achromatic quarter-wave plate, and one spectrometer. This system is flexible from UV to IR region, only depending on the power spectra of light source and sensitivity of the detector at the corresponding wavelengths. As examples, we measured the intriguing optic and MO activity in glass, ferromagnetic thin film, and bulk GaAs in the visible to near infrared region. The results of glass demonstrated a minimum resolvable Faraday rotation angle of 0.004 degrees by the currently equipped system. PMID- 22299926 TI - Fully programmable single-photon detection module for InGaAs/InP single-photon avalanche diodes with clean and sub-nanosecond gating transitions. AB - We present the design and characterization of a modern near-infrared photon counting module, able to exploit the best performance of InGaAs/InP single-photon avalanche diodes for the detection of fast and faint optical signals up to 1.7 MUm. Such instrument is suitable for many applications, thanks to the user friendly interface and the fully adjustable settings of all operating parameters. We extensively characterized both the electronics and the detector, and we validated such instrument up to 133 MHz gate repetition frequency, for photon counting and photon-timing applications, with very clean temporal response and excellent timing performance of less than 100 ps. PMID- 22299927 TI - Magnetic transport apparatus for the production of ultracold atomic gases in the vicinity of a dielectric surface. AB - We present an apparatus designed for studies of atom-surface interactions using quantum degenerate gases of (85)Rb and (87)Rb in the vicinity of a room temperature dielectric surface. The surface to be investigated is a super polished face of a glass Dove prism mounted in a glass cell under ultra-high vacuum. To maintain excellent optical access to the region surrounding the surface, magnetic transport is used to deliver ultracold atoms from a separate vacuum chamber housing the magneto-optical trap (MOT). We present a detailed description of the vacuum apparatus highlighting the novel design features; a low profile MOT chamber and the inclusion of an obstacle in the transport path. We report the characterization and optimization of the magnetic transport around the obstacle, achieving transport efficiencies of 70% with negligible heating. Finally, we demonstrate the loading of a hybrid optical-magnetic trap with (87)Rb and the creation of Bose-Einstein condensates via forced evaporative cooling close to the dielectric surface. PMID- 22299928 TI - A dual-channel, focusing x-ray spectrograph with uniform dispersion for Z pinch plasmas measurement. AB - A dual-channel, focusing x-ray spectrograph with uniform dispersion (i.e., the linear dispersion of this spectrograph is a constant) is described for measuring the x-ray spectra emission from the hot, dense Al Z pinch plasmas. The spectrograph uses double uniform-dispersed crystals (e.g., a Quartz 1010 crystal and a Mica 002 crystal) as dispersion elements and a double-film box as detector to achieve the simultaneous recording of the time integrated spectrum covering a wide spectral range of ~5-9 A. Since this spectrograph disperse the x-rays on the detector plane with uniform spacing for every wavelength, it needs not the calibration of the wavelength with spatial coordinate, thereby own the advantages of easiness and veracity for spectra identification. The design of this spectrograph and the example of experiment on the "Yang" accelerator are presented. PMID- 22299929 TI - An optically pumped XeF(C-A) laser with repetitive rate of 10 Hz. AB - A novel XeF(C-A) laser which can be operated in repetition mode has been developed based on surface discharge optical pumping technique. Its maximum repetitive rate is up to 10 Hz. The influence of repetitive rate and gas flow rate on the stability of output energy is studied and the main factor which influences the stability of output energy is analyzed. The experimental results show that increasing the gas flow rate into laser chamber can improve the stability of the output energy. The ideal output energy results of 20 laser pulses under different repetitive rates and their optimal experimental conditions are presented. Output energies of more than 4 J and better stability can be obtained when the laser device operates at 1, 2, and 5 Hz, respectively. When the gas feed rate is larger than 53 l/s, the stability of output energy is improved obviously at the repetitive rate of 10 Hz, and the average energy of 20 laser pulses is up to 3.2 J. PMID- 22299930 TI - Positive/negative ion velocity mapping apparatus for electron-molecule reactions. AB - In molecular dissociative ionization by electron collisions and dissociative electron attachment to molecule, the respective positively and negatively charged fragments are the important products. A compact ion velocity mapping apparatus is developed for the angular distribution measurements of the positive or negative fragments produced in the electron-molecule reactions. This apparatus consists of a pulsed electron gun, a set of ion velocity mapping optic lenses, a two dimensional position detector including two pieces of micro-channel plates, and a phosphor screen, and a charge-coupled-device camera for data acquisition. The positive and negative ion detections can be simply realized by changing the voltage polarity of ion optics and detector. Velocity sliced images can be directly recorded using a narrow voltage pulse applied on the rear micro-channel plate. The efficient performance of this system is evaluated by measuring the angular distribution of O(-) from the electron attachments to NO at 7.3 and 8.3 eV and O(+) from the electron collision with CO at 40.0 eV. PMID- 22299931 TI - A high accuracy femto-/picosecond laser damage test facility dedicated to the study of optical thin films. AB - A laser damage test facility delivering pulses from 100 fs to 3 ps and designed to operate at 1030 nm is presented. The different details of its implementation and performances are given. The originality of this system relies the online damage detection system based on Nomarski microscopy and the use of a non conventional energy detection method based on the utilization of a cooled CCD that offers the possibility to obtain the laser induced damage threshold (LIDT) with high accuracy. Applications of this instrument to study thin films under laser irradiation are presented. Particularly the deterministic behavior of the sub-picosecond damage is investigated in the case of fused silica and oxide films. It is demonstrated that the transition of 0-1 damage probability is very sharp and the LIDT is perfectly deterministic at few hundreds of femtoseconds. The damage process in dielectric materials being the results of electronic processes, specific information such as the material bandgap is needed for the interpretation of results and applications of scaling laws. A review of the different approaches for the estimation of the absorption gap of optical dielectric coatings is conducted and the results given by the different methods are compared and discussed. The LIDT and gap of several oxide materials are then measured with the presented instrument: Al(2)O(3), Nb(2)O(5), HfO(2), SiO(2), Ta(2)O(5), and ZrO(2). The obtained relation between the LIDT and gap at 1030 nm confirms the linear evolution of the threshold with the bandgap that exists at 800 nm, and our work expands the number of tested materials. PMID- 22299932 TI - Total internal reflection fluorescence microscopy imaging-guided confocal single molecule fluorescence spectroscopy. AB - We have developed an integrated spectroscopy system combining total internal reflection fluorescence microscopy imaging with confocal single-molecule fluorescence spectroscopy for two-dimensional interfaces. This spectroscopy approach is capable of both multiple molecules simultaneously sampling and in situ confocal fluorescence dynamics analyses of individual molecules of interest. We have demonstrated the calibration with fluorescent microspheres, and carried out single-molecule spectroscopy measurements. This integrated single-molecule spectroscopy is powerful in studies of single molecule dynamics at interfaces of biological and chemical systems. PMID- 22299933 TI - Two beam surface fluctuation specular reflection spectroscopy. AB - In surface fluctuation specular reflection spectroscopy (SFSRS) deflections of a specularly reflected laser beam are used to characterize thermally excited surface waves. Here we report on a new two beam version of SFSRS in which the deflections of two reflected laser beams from separate locations on a surface are correlated. We demonstrate that this new two beam SFSRS technique can be used to determine directly the power spectrum of height fluctuation of thermally excited surface waves over a large range of both frequencies and wavevectors. In addition, we show that the technique is well suited for materials ranging from simple liquids to complex liquids and soft solids, including turbid materials. PMID- 22299934 TI - One-shot spectrometer for several elements using an integrated conical crystal analyzer. AB - Time-resolved x-ray spectrometry using an ultrastrong x-ray source such as an x ray free electron laser is one of the new trends in the field of x-ray physics. To achieve such time-resolved measurement, the development of an one-shot spectrometer with a wide wavelength range, high efficiency, and good energy resolution is an essential prerequisite. Here we developed an integrated conical Ge crystal analyzer consisting of several conical rings, which were connected using spline surfaces to form a single body using our previously developed hot deformation technique, which can form a Si or Ge wafer into an arbitrary and accurate shape. We simultaneously focused several characteristic lines from an alloy sample onto different positions on a small x-ray charge-coupled device with very high image brightness (gain relative to planar analyzer: 100) and a good spatial resolution of 9-13 eV. The small radius of curvature of the crystal (28 50 mm) enabled us to realize a very short sample-detector distance of 214.4 mm. The present result shows the possibility of realizing a new focusing x-ray crystal spectrograph that can control the focal position as desired. PMID- 22299935 TI - Time-resolved one-dimensional detection of x-ray scattering in pulsed magnetic fields. AB - We have developed an application of a one-dimensional micro-strip detector for capturing x-ray diffraction data in pulsed magnetic fields. This detector consists of a large array of 50 MUm-wide Si strips with a full-frame read out at 20 kHz. Its use substantially improves data-collection efficiency and quality as compared to point detectors, because diffraction signals are recorded along an arc in reciprocal space in a time-resolved manner. By synchronizing with pulsed fields, the entire field dependence of a two-dimensional swath of reciprocal space may be determined using a small number of field pulses. PMID- 22299936 TI - Improving metastable impact electron spectroscopy and ultraviolet photoelectron spectroscopy signals by means of a modified time-of-flight separation. AB - The separation of ultraviolet photoelectron spectroscopy (UPS) and metastable impact electron spectroscopy (MIES) is usually performed by a time-of-flight (ToF) separation using pre-set ToF for both types of signal. In this work, we present a new, improved ex situ signal separation method for the separation of MIES and UPS for every single measurement. Signal separation issues due to changes of system parameters can be overcome by changing the ToF separation and therefore allowing for the application of a wider range of measuring conditions. The method also enables to identify and achieve separation of the two signals without any time consuming calibration and the use of any special material for the calibration. Furthermore, changes made to the discharge source are described that enable to operate an existing MIES/UPS source over a broader range of conditions. This allows for tuning of the yield of UV photons and metastable rare gas atoms leading to an improved signal to noise ratio. First results of this improved setup are well in agreement with spectra reported in literature and show increased resolution and higher signal intensities for both MIE and UP spectra compared to the previous, non-optimized setup. PMID- 22299937 TI - Versatile high-repetition-rate phase-locked chopper system for fast timing experiments in the vacuum ultraviolet and x-ray spectral region. AB - A novel light chopper system for fast timing experiments in the vacuum ultraviolet (VUV) and x-ray spectral region has been developed. It can be phase locked and synchronized with a synchrotron radiation storage ring, accommodating repetition rates in the range of ~8 to ~120 kHz by choosing different sets of apertures and subharmonics of the ring frequency (MHz range). Also the opening time of the system can be varied from some nanoseconds to several microseconds to meet the needs of a broad range of applications. Adjusting these parameters, the device can be used either for the generation of single light pulses or pulse packages from a microwave driven, continuous He gas discharge lamp or from storage rings which are otherwise often considered as quasi-continuous light sources. This chopper can be utilized for many different kinds of experiments enabling, for example, unambiguous time-of-flight (TOF) multi-electron coincidence studies of atoms and molecules excited by a single light pulse as well as time-resolved visible laser pump x-ray probe electron spectroscopy of condensed matter in the valence and core level region. PMID- 22299938 TI - Ultrahigh resolution soft x-ray emission spectrometer at BL07LSU in SPring-8. AB - An extremely high resolution flat field type slit less soft x-ray emission spectrometer has been designed and constructed for the long undulator beamline BL07LSU in SPring-8. By optimizing the ruling parameters of two cylindrical gratings, a high energy resolution DeltaE < 100 meV and/or an E/DeltaE ~ 10 000 are expected for the energy range of 350 eV - 750 eV taking into account the broadening by the spatial resolution (25 MUm) of a CCD detector. A coma-free operation mode proposed by Strocov et al., is also applied to eliminate both defocus and coma aberrations. The spectrometer demonstrated experimentally that E/DeltaE = 10 050 and 8046 for N 1s (402.1 eV) and Mn 2p (641.8 eV) edges, respectively. PMID- 22299939 TI - Arc discharge regulation of a megawatt hot cathode bucket ion source for the experimental advanced superconducting tokamak neutral beam injector. AB - Arc discharge of a hot cathode bucket ion source tends to be unstable what attributes to the filament self-heating and energetic electrons backstreaming from the accelerator. A regulation method, which based on the ion density measurement by a Langmuir probe, is employed for stable arc discharge operation and long pulse ion beam generation. Long pulse arc discharge of 100 s is obtained based on this regulation method of arc power. It establishes a foundation for the long pulse arc discharge of a megawatt ion source, which will be utilized a high power neutral beam injection device. PMID- 22299940 TI - Electron spectrometer in adjustable triode configuration for photo-induced field emission measurements. AB - We have constructed a new ultrahigh vacuum apparatus with a triode configuration for the systematic investigation of photo-induced field emission (PFE) from metallic or semiconducting cathodes. These are exposed to electric fields up to 400 MV/m and laser irradiation by means of hole or mesh gates. Cathodes and gates are in situ exchangeable and adjustable with high precision to ensure a homogeneous extraction of electrons which are partially transmitted to the fixed electron spectrometer. Its hemispherical sector analyzer provides an energy resolution limit of 8 meV. The commissioning of the measurement system has been performed with a tungsten needle. Its temperature showed up in the high-energy tail of the electron spectrum, while its work function was derived from the spectral low-energy part combined with the integral current-voltage curve. First PFE measurements on B-doped Si-tip arrays yielded a small field emission current increase under green laser illumination. A shift and splitting of the energy spectra was observed which revealed different emission regimes as well as the photosensitivity of the cathode due to carrier excitation into the conduction band. For the full exploitation of the PFE system, a tunable laser over a wide eV range is required. PMID- 22299941 TI - A very low energy compact electron beam ion trap for spectroscopic research in Shanghai. AB - In this paper, a new compact low energy electron beam ion trap, SH-PermEBIT, is reported. This electron beam ion trap (EBIT) can operate in the electron energy range of 60-5000 eV, with a current density of up to 100 A/cm(2). The low energy limit of this machine sets the record among the reported works so far. The magnetic field in the central drift tube region of this EBIT is around 0.5 T, produced by permanent magnets and soft iron. The design of this EBIT allows adjustment of the electron gun's axial position in the fringe field of the central magnetic field. This turned out to be very important for optimizing the magnetic field in the region of the electron gun and particularly important for low electron beam energy operation, since the magnetic field strength is not tunable with permanent magnets. In this work, transmission of the electron beam as well as the upper limit of the electron beam width under several conditions are measured. Spectral results from test operation of this EBIT at the electron energies of 60, 315, 2800, and 4100 eV are also reported. PMID- 22299942 TI - A new detector for mass spectrometry: direct detection of low energy ions using a multi-pixel photon counter. AB - A new type of ion detector for mass spectrometry and general detection of low energy ions is presented. The detector consists of a scintillator optically coupled to a single-photon avalanche photodiode (SPAD) array. A prototype sensor has been constructed from a LYSO (Lu(1.8)Y(0.2)SiO(5)(Ce)) scintillator crystal coupled to a commercial SPAD array detector. As proof of concept, the detector is used to record the time-of-flight mass spectra of butanone and carbon disulphide, and the dependence of detection sensitivity on the ion kinetic energy is characterised. PMID- 22299943 TI - A new experimental setup designed for the investigation of irradiation of nanosystems in the gas phase: a high intensity mass-and-energy selected cluster beam. AB - DIAM (Dispositif d'Irradiation d'Agregats Moleculaires) is a new experimental setup devoted to investigate processes induced by irradiation at the nanoscale. The DIAM apparatus is based on a combination of techniques including a particle beam from high-energy physics, a cluster source from molecular and cluster physics, and mass spectrometry form analytical sciences. In this paper, we will describe the first part of the DIAM apparatus that consists of an ExB double spectrometer connected to a cluster ion source based on a continuous supersonic expansion in the presence of ionizing electrons. This setup produces high intensities of energy-and-mass selected molecular cluster ion beams (1000 s of counts s(-1)). The performance of the instrument will be shown through measurements of 6-8 keV beams of protonated water clusters, (H(2)O)(n)H(+) (n = 0 21) and mixed protonated (or deprotonated) water-pyridine cluster ions: PyrH(+)(H(2)O)(n) (n = 0-15), Pyr(2)H(+) (H(2)O)(n) (n = 0-9), and (Pyr-H)(+) (H(2)O). PMID- 22299944 TI - In situ calibration of rotating sensor coils for magnet testing. AB - An in situ procedure for calibrating equivalent magnetic area and rotation radius of rotating coils is proposed for testing accelerator magnets shorter than the measuring coil. The procedure exploits measurements of magnetic field and mechanical displacement inside a reference quadrupole magnet. In a quadrupole field, an offset between the magnet and coil rotation axes gives rise to a dipole component in the field series expansion. The measurements of the focusing strength, the displacement, and the resulting dipole term allow the equivalent area and radius of the coil to be determined analytically. The procedure improves the accuracy of coils with large geometrical irregularities in the winding. This is essential for short magnets where the coil dimensions constrain the measurement accuracy. Experimental results on different coils measuring small aperture permanent magnets are shown. PMID- 22299945 TI - Investigation of a high spatial resolution method based on polar coordinate maximum entropy method for analyzing electron density fluctuation data measured by laser phase contrast. AB - Laser phase contrast is a powerful diagnostic method to determine the spatial distribution of electron density fluctuations in magnetically confined plasmas, although its applicability depends on magnetic field configurations. The spatial resolution of fluctuations is linked with the resolution of the propagation direction that is derived from the two-dimensional spectral analysis of the wavenumber for the fluctuations. The method was applied to fluctuation measurements in a compact helical system. In order to improve the resolution of the propagation direction with a relatively small number of data points, the maximum entropy method with polar coordinates was employed. A spatial resolution of the order of 1 cm was obtained, which is satisfactory in a plasma with a 20 cm minor radius. PMID- 22299946 TI - A high dynamic range data acquisition system for a solid-state electron electric dipole moment experiment. AB - We have built a high precision (24-bit) data acquisition (DAQ) system capable of simultaneously sampling eight input channels for the measurement of the electric dipole moment of the electron. The DAQ system consists of two main components: a master board for DAQ control and eight individual analog-to-digital converter (ADC) boards for signal processing. This custom DAQ system provides galvanic isolation of the ADC boards from each other and the master board using fiber optic communication to reduce the possibility of ground loop pickup and attain ultimate low levels of channel cross-talk. In this paper, we describe the implementation of the DAQ system and scrutinize its performance. PMID- 22299947 TI - Electrical test method using high density plasmas for high-end printed circuit boards. AB - A novel electrical test method that uses high-density plasmas, such as inductively coupled discharges, is proposed to detect open/short failures of high end printed circuit boards (PCBs). The PCB is inserted into the plasma chamber with the top side facing the plasma sheath, and the bottom of the PCB is connected to the probe pin for the dc voltage bias and current measurements. A failure, including a latent open, can be precisely detected by biasing the dc voltage near the plasma potential due to the specific characteristics of the sheath formed on the PCB surface. PMID- 22299948 TI - Study on erosion mechanism of graphite electrode in two-electrode spark gap switch. AB - In a high-powered single pulse system, the graphite electrode is better than other common metal electrodes for high energy transfer and pulse discharge. In this paper, the erosion mechanism of graphite electrode is investigated with the thermodynamics theory and the experimental results. Based on a simplified mathematical model, the graphite electrode erosion process of high-powered spark gap switch is also analyzed. The analysis results show that the relationship of the graphite electrode erosion and the charge transfer is linear, which is accordant with the experimental results. PMID- 22299949 TI - Movable magnetic probe system in the T-10 tokamak. AB - New magnetic probe system is installed on the T-10 tokamak to investigate fast scale magnetic perturbations (f up to 2 MHz). The system is based on vertical and horizontal magnetic probes made by nickel wire in glass enamel isolation (effective area 20-250 cm(2)) separated from the support structures by ceramic spacers (5-10 mm). The probe system is mounted on the top of movable rode allowing positioning along vertical axis close to the plasma boundary at the low field side of the torus. Additional positioning system allows rotation of the probes around the vertical axis on pulse-to-pulse basis. The probes are directly connected to the analog-to-digital converter (ADC) module (acquisition rate 60 MHz) through short (~4 m) coaxial cables. The system allowed identification of the fast-scale magnetic oscillations (0.2-0.5 MHz) during energy quench phase of the disruption instability in plasma with high density. Amplitude of the fast scale magnetic oscillations decays with distance from the plasma boundary 2-10 times faster than one of the standard magnetohydrodynamic modes. PMID- 22299950 TI - Spatial resolution of the JET Thomson scattering system. AB - The instrument function of the high resolution Thomson scattering (HRTS) diagnostic in the Joint European Torus (JET) has been calculated for use in improved pedestal profile analysis. The full width at half maximum (FWHM) of the spatial instrument response is (22 +/- 1) mm for the original HRTS system configuration and depends on the particular magnetic topology of the JET plasmas. An improvement to the optical design of the laser input system is presented. The spatial smearing across magnetic flux surfaces is reduced in this design. The new input system has been implemented (from JPN 78742, July 2009) and the HRTS instrument function corresponding to the new configuration has been improved to approximately FWHM = (9.8 +/- 0.8) mm. The reconstructed instrument kernels are used in combination with an ad hoc forward deconvolution procedure for pedestal analysis. This procedure produces good results for both the old and new setups, but the reliability of the deconvolved profiles is greatly reduced when the pedestal width is of the same order as, or less than the FWHM of the instrument kernel. PMID- 22299951 TI - Design and performance of the collective Thomson scattering receiver at ASDEX Upgrade. AB - Here we present the design of the fast-ion collective Thomson scattering receiver for millimeter wave radiation installed at ASDEX Upgrade, a tokamak for fusion plasma experiments. The receiver can detect spectral power densities of a few eV against the electron cyclotron emission background on the order of 100 eV under presence of gyrotron stray radiation that is several orders of magnitude stronger than the signal to be detected. The receiver down converts the frequencies of scattered radiation (100-110 GHz) to intermediate frequencies (IF) (4.5-14.5 GHz) by heterodyning. The IF signal is divided into 50 IF channels tightly spaced in frequency space. The channels are terminated by square-law detector diodes that convert the signal power into DC voltages. We present measurements of the transmission characteristics and performance of the main receiver components operating at mm-wave frequencies (notch, bandpass, and lowpass filters, a voltage controlled variable attenuator, and an isolator), the down-converter unit, and the IF components (amplifiers, bandpass filters, and detector diodes). Furthermore, we determine the performance of the receiver as a unit through spectral response measurements and find reasonable agreement with the expectation based on the individual component measurements. PMID- 22299952 TI - Beam emission spectroscopy turbulence imaging system for the MAST spherical tokamak. AB - A new beam emission spectroscopy turbulence imaging system has recently been installed onto the MAST spherical tokamak. The system utilises a high-throughput, direct coupled imaging optics, and a single large interference filter for collection of the Doppler shifted D(alpha) emission from the ~2 MW heating beam of ~70 keV injection energy. The collected light is imaged onto a 2D array detector with 8 * 4 avalanche photodiode sensors which is incorporated into a custom camera unit to perform simultaneous 14-bit digitization at 2 MHz of all 32 channels. The array is imaged at the beam to achieve a spatial resolution of ~2 cm in the radial (horizontal) and poloidal (vertical) directions, which is sufficient for detection of the ion-scale plasma turbulence. At the typical photon fluxes of ~10(11) s(-1) the achieved signal-to-noise ratio of ~300 at the 0.5 MHz analogue bandwidth is sufficient for detection of relative density fluctuations at the level of a few 0.1%. The system is to be utilised for the study of the characteristics of the broadband, ion-scale turbulence, in particular its interaction with flow shear, as well as coherent fluctuations due to various types of MHD activity. PMID- 22299953 TI - Spectroscopic reflectometry of mirror surfaces during plasma exposure. AB - An in situ spectroscopic reflectometry system has been built to investigate the evolution of the specular reflectivity spectrum of ITER first mirror samples during plasma exposure. Results are presented for three different types of molybdenum mirror samples that were exposed to deuterium plasma, including single crystalline, nanocrystalline, and polycrystalline molybdenum. The results show good agreement with ex situ measurements of the reflectivity spectrum before and after exposure and extend the results obtained in previous experiments. PMID- 22299954 TI - Cutoff probe using Fourier analysis for electron density measurement. AB - This paper proposes a new method for cutoff probe using a nanosecond impulse generator and an oscilloscope, instead of a network analyzer. The nanosecond impulse generator supplies a radiating signal of broadband frequency spectrum simultaneously without frequency sweeping, while frequency sweeping method is used by a network analyzer in a previous method. The transmission spectrum (S21) was obtained through a Fourier analysis of the transmitted impulse signal detected by the oscilloscope and was used to measure the electron density. The results showed that the transmission frequency spectrum and the electron density obtained with a new method are very close to those obtained with a previous method using a network analyzer. And also, only 15 ns long signal was necessary for spectrum reconstruction. These results were also compared to the Langmuir probe's measurements with satisfactory results. This method is expected to provide not only fast measurement of absolute electron density, but also function in other diagnostic situations where a network analyzer would be used (a hairpin probe and an impedance probe) by replacing the network analyzer with a nanosecond impulse generator and an oscilloscope. PMID- 22299955 TI - Using high-intensity laser-generated energetic protons to radiograph directly driven implosions. AB - The recent development of petawatt-class lasers with kilojoule-picosecond pulses, such as OMEGA EP [L. Waxer et al., Opt. Photonics News 16, 30 (2005)], provides a new diagnostic capability to study inertial-confinement-fusion (ICF) and high energy-density (HED) plasmas. Specifically, petawatt OMEGA EP pulses have been used to backlight OMEGA implosions with energetic proton beams generated through the target normal sheath acceleration (TNSA) mechanism. This allows time-resolved studies of the mass distribution and electromagnetic field structures in ICF and HED plasmas. This principle has been previously demonstrated using Vulcan to backlight six-beam implosions [A. J. Mackinnon et al., Phys. Rev. Lett. 97, 045001 (2006)]. The TNSA proton backlighter offers better spatial and temporal resolution but poorer spatial uniformity and energy resolution than previous D(3)He fusion-based techniques [C. Li et al., Rev. Sci. Instrum. 77, 10E725 (2006)]. A target and the experimental design technique to mitigate potential problems in using TNSA backlighting to study full-energy implosions is discussed. The first proton radiographs of 60-beam spherical OMEGA implosions using the techniques discussed in this paper are presented. Sample radiographs and suggestions for troubleshooting failed radiography shots using TNSA backlighting are given, and future applications of this technique at OMEGA and the NIF are discussed. PMID- 22299956 TI - Probing local surface conductance using current sensing atomic force microscopy. AB - We have analyzed correlations between surface morphology and current sensing images obtained using a current sensing atomic force microscope (CSAFM) and the implication of surface conductivity derived from the current sensing images. We found that in cases where the diameter of a CSAFM probe tip is much smaller than the correlation length of the surface morphological features, the current detected using the probe should have little correlation with the surface features imaged by the same probe. If the sample thickness is much larger than the tip size, the surface conductivity distribution of a sample can be derived from a current sensing image using the Holm resistance relation, and the current probed using a CSAFM reflects the conductance variations in a layer on the surface with the thickness comparable to the probe diameter. However, if the thickness of a sample is comparable to or smaller than the tip diameter, CSAFM measures the conductance across the entire portion of the sample sandwiched between the tip and the electrode. PMID- 22299957 TI - Gaining insight into the physics of dynamic atomic force microscopy in complex environments using the VEDA simulator. AB - Dynamic atomic force microscopy (dAFM) continues to grow in popularity among scientists in many different fields, and research on new methods and operating modes continues to expand the resolution, capabilities, and types of samples that can be studied. But many promising increases in capability are accompanied by increases in complexity. Indeed, interpreting modern dAFM data can be challenging, especially on complicated material systems, or in liquid environments where the behavior is often contrary to what is known in air or vacuum environments. Mathematical simulations have proven to be an effective tool in providing physical insight into these non-intuitive systems. In this article we describe recent developments in the VEDA (virtual environment for dynamic AFM) simulator, which is a suite of freely available, open-source simulation tools that are delivered through the cloud computing cyber-infrastructure of nanoHUB (www.nanohub.org). Here we describe three major developments. First, simulations in liquid environments are improved by enhancements in the modeling of cantilever dynamics, excitation methods, and solvation shell forces. Second, VEDA is now able to simulate many new advanced modes of operation (bimodal, phase-modulation, frequency-modulation, etc.). Finally, nineteen different tip-sample models are available to simulate the surface physics of a wide variety different material systems including capillary, specific adhesion, van der Waals, electrostatic, viscoelasticity, and hydration forces. These features are demonstrated through example simulations and validated against experimental data, in order to provide insight into practical problems in dynamic AFM. PMID- 22299958 TI - Anti-drift and auto-alignment mechanism for an astigmatic atomic force microscope system based on a digital versatile disk optical head. AB - In this work, an anti-drift and auto-alignment mechanism is applied to an astigmatic detection system (ADS)-based atomic force microscope (AFM) for drift compensation and cantilever alignment. The optical path of the ADS adopts a commercial digital versatile disc (DVD) optical head using the astigmatic focus error signal. The ADS-based astigmatic AFM is lightweight, compact size, low priced, and easy to use. Furthermore, the optical head is capable of measuring sub-atomic displacements of high-frequency AFM probes with a sub-micron laser spot (~570 nm, FWHM) and a high-working bandwidth (80 MHz). Nevertheless, conventional DVD optical heads suffer from signal drift problems. In a previous setup, signal drifts of even thousands of nanometers had been measured. With the anti-drift and auto-alignment mechanism, the signal drift is compensated by actuating a voice coil motor of the DVD optical head. A nearly zero signal drift was achieved. Additional benefits of this mechanism are automatic cantilever alignment and simplified design. PMID- 22299959 TI - Study of thermal and acoustic noise interferences in low stiffness atomic force microscope cantilevers and characterization of their dynamic properties. AB - The atomic force microscope (AFM) is a powerful tool for the measurement of forces at the micro/nano scale when calibrated cantilevers are used. Besides many existing calibration techniques, the thermal calibration is one of the simplest and fastest methods for the dynamic characterization of an AFM cantilever. This method is efficient provided that the Brownian motion (thermal noise) is the most important source of excitation during the calibration process. Otherwise, the value of spring constant is underestimated. This paper investigates noise interference ranges in low stiffness AFM cantilevers taking into account thermal fluctuations and acoustic pressures as two main sources of noise. As a result, a preliminary knowledge about the conditions in which thermal fluctuations and acoustic pressures have closely the same effect on the AFM cantilever (noise interference) is provided with both theoretical and experimental arguments. Consequently, beyond the noise interference range, commercial low stiffness AFM cantilevers are calibrated in two ways: using the thermal noise (in a wide temperature range) and acoustic pressures generated by a loudspeaker. We then demonstrate that acoustic noises can also be used for an efficient characterization and calibration of low stiffness AFM cantilevers. The accuracy of the acoustic characterization is evaluated by comparison with results from the thermal calibration. PMID- 22299960 TI - Circular multilayer zone plate for high-energy x-ray nano-imaging. AB - A circular multilayer zone plate (MZP) was fabricated and its focusing performance was evaluated using 20-keV x-rays. MoSi(2) and Si layers were alternately deposited by DC magnetron sputtering on a wire core; all the interfaces satisfied the Fresnel zone condition. The measured line spread function was converted to a point spread function by tomographic reconstruction. The results suggest that the MZP has the potential to realize the diffraction limited resolving power, which is calculated to be 35 nm using the diffraction integral. Furthermore, scanning transmission microscopy using the MZP could resolve a 50-nm line-and-space pattern. PMID- 22299961 TI - Rapid measurement of a high step microstructure with 90 degrees steep sidewall. AB - A prototype STM system with high aspect ratio measurement capability is developed to fulfill accurate profile measurement of a high step microstructure with 90 degrees steep sidewall. Distinguished from the traditional STM, the new system consists of a long range piezoelectric (PZT) actuator with full stroke of 60 MUm as Z-direction servo scanner, a specially customized high aspect ratio STM probe with effective tip length of 300 MUm, and an X-Y motorized driven stage for planar scanning. A tilt stage is used to adjust the probe-sample relative angle to compensate the evitable non-parallel effects. Based on the new STM system, sample-tilt-scanning methodology is proposed for eliminating the scanning blind region between the probe and the microstructure. A high step microstructure with height of 23 MUm, 90 degrees steep sidewall and width of 50MUm has been successfully measured. The slope angle of the sidewall has been achieved to be 85 degrees and the step height at the rising edge and the trench depth at the falling edge are both measured to be 22.96 MUm. The whole measuring process only spent less than 10 min. It provides an effective and nondestructive solution for the measurement of high step or deep trench microstructures. In addition, this work also opens the way for further study on sidewall roughness and the tip sample interaction at the edge of the sidewall, which are highly valuable for fabrication and quality control of high step microstructures. PMID- 22299962 TI - High-speed force load in force measurement in liquid using scanning probe microscope. AB - This article presents an inversion-based iterative feedforward-feedback (II FF/FB) approach to achieve high-speed force load in force measurement of soft materials in liquid using scanning probe microscope (SPM). SPM force measurement under liquid environment is needed to interrogate a wide range of soft materials, particularly live biological samples. Moreover, when dynamic evolution of the sample occurs during the measurement, and/or measuring the rate-dependent viscoelasticity of the sample, the force measurement also needs to be acquired at high-speed. Precision force load in liquid, however, is challenged by adverse effects including the thermal drift effect, the reduction of the signal to noise ratio, the distributive hydrodynamic force effect, and the hysteresis and vibrational dynamics effects of the piezoelectric actuators (for positioning the probe relative to the sample), particularly during high-speed measurement. Thus, the main contribution of the article is the development of the II-FF/FB approach to tackle these challenges. The proposed method is illustrated through an experimental implementation to the force-curve measurement of a poly (dimethylsiloxane) sample in liquid at high-speed. PMID- 22299963 TI - Simple electronics for inertial and Pan-type piezoelectric positioners used in scanning probe microscopes. AB - We describe a new type of circuit designed for driving piezoelectric positioners that rely on the stick-slip phenomenon. The circuit can be used for inertial positioners that have only one piezoelectric element (or multiple elements that are moved simultaneously) or for designs using a sequential movement of independent piezoelectric elements. A relay switches the piezoelectric elements between a high voltage source and ground, thus creating a fast voltage step followed by a slow ramp produced by the exponential discharging of the piezoelectric elements through a series resistor. A timing cascade is generated by having each relay power the next relay in the sequence. This design is simple and inexpensive. While it was developed for scanning probe microscopes, it may be useful for any piezoelectric motor based on a fast jump followed by a slow relaxation. PMID- 22299964 TI - Improving the precision of Hall effect measurements using a single-crystal copper probe. AB - The circuitry and components of a Hall measurement kit were replaced with single crystal copper (SCC) wires and parts prepared by a novel wire fabrication process. This process preserved the grain-free structure of SCC grown by the Czochralski method. The new kit was used to determine, with greatly improved precision, the electrical coefficients such as carrier density and mobility, establish the reproducibility of the measured values, and define the semiconductor type. The observed reduction in electrical signal losses and distortion has been attributed to grain boundary elimination. PMID- 22299965 TI - Online in situ x-ray diffraction setup for structural modification studies during swift heavy ion irradiation. AB - The high energy density of electronic excitations due to the impact of swift heavy ions can induce structural modifications in materials. We present an x-ray diffractometer called ALIX ("Analyse en Ligne sur IRRSUD par diffraction de rayons X"), which has been set up at the low-energy beamline (IRRadiation SUD - IRRSUD) of the Grand Accelerateur National d'Ions Lourds facility, to allow the study of structural modification kinetics as a function of the ion fluence. The x ray setup has been modified and optimized to enable irradiation by swift heavy ions simultaneously to x-ray pattern recording. We present the capability of ALIX to perform simultaneous irradiation-diffraction by using energy discrimination between x-rays from diffraction and from ion-target interaction. To illustrate its potential, results of sequential or simultaneous irradiation-diffraction are presented in this article to show radiation effects on the structural properties of ceramics. Phase transition kinetics have been studied during xenon ion irradiation of polycrystalline MgO and SrTiO(3). We have observed that MgO oxide is radiation-resistant to high electronic excitations, contrary to the high sensitivity of SrTiO(3), which exhibits transition from the crystalline to the amorphous state during irradiation. By interpreting the amorphization kinetics of SrTiO(3), defect overlapping models are discussed as well as latent track characteristics. Together with a transmission electron microscopy study, we conclude that a single impact model describes the phase transition mechanism. PMID- 22299966 TI - A versatile cantilever beam magnetometer for ex situ characterization of magnetic materials. AB - We have designed, fabricated, and made operational an ex situ cantilever beam magnetometer (CBM), which is versatile in the sense that it can measure most of the magnetic properties of a material in all probable shapes. The working principle of a CBM is discussed considering the magnetic torque into the beam theory. The individual components of the instrument are described in details and experiments were performed on the bulk materials, pellets of nanoparticles, ribbon samples, and thin films, and the magnetization, magnetostriction, and magnetocrystalline anisotropy were studied. This magnetometer is inexpensive, but versatile and would be suitable for the research as well as teaching laboratories. PMID- 22299967 TI - An in situ approach to study trace element partitioning in the laser heated diamond anvil cell. AB - Data on partitioning behavior of elements between different phases at in situ conditions are crucial for the understanding of element mobility especially for geochemical studies. Here, we present results of in situ partitioning of trace elements (Zr, Pd, and Ru) between silicate and iron melts, up to 50 GPa and 4200 K, using a modified laser heated diamond anvil cell (DAC). This new experimental set up allows simultaneous collection of x-ray fluorescence (XRF) and x-ray diffraction (XRD) data as a function of time using the high pressure beamline ID27 (ESRF, France). The technique enables the simultaneous detection of sample melting based to the appearance of diffuse scattering in the XRD pattern, characteristic of the structure factor of liquids, and measurements of elemental partitioning of the sample using XRF, before, during and after laser heating in the DAC. We were able to detect elements concentrations as low as a few ppm level (2-5 ppm) on standard solutions. In situ measurements are complimented by mapping of the chemical partitions of the trace elements after laser heating on the quenched samples to constrain the partitioning data. Our first results indicate a strong partitioning of Pd and Ru into the metallic phase, while Zr remains clearly incompatible with iron. This novel approach extends the pressure and temperature range of partitioning experiments derived from quenched samples from the large volume presses and could bring new insight to the early history of Earth. PMID- 22299968 TI - An ultrashort-duration, high-repetition-rate pulse source for laser ionization/mass spectrometry. AB - This paper describes a sample inlet system with several advantages over other pulsed valves, as applied to resonance-enhanced multiphoton ionization/time-of flight mass spectrometry. The nozzle is based on online concentration by analyte adsorption/laser desorption (online COLD), where a capillary column with a narrowly synthesized tip is employed for sample introduction. The analyte molecules adsorbed at the tip are desorbed by a pulsed laser and are injected into a mass spectrometer as a packet. The online COLD nozzle can produce very short gas pulses on the order of 1 MUs. Moreover, this nozzle is capable of operating over a wide range of repetition rates from 1 Hz to 1 kHz. In addition, this nozzle intrinsically possesses several unique characteristics; for instance, it can be heated to very high temperatures and has nearly zero dead volume. Therefore, the present sample introduction technique offers an ideal and versatile nozzle for laser ionization/mass spectrometry. PMID- 22299969 TI - A two-color tunable infrared/vacuum ultraviolet spectrometer for high-resolution spectroscopy of molecules in molecular beams. AB - We describe here the key technical elements of a two-color tunable IR/VUV photoionization TOF mass spectrometer system which allows a wide-range of high resolution experiments to be performed on a diverse range of cold molecules and clusters in a molecular beam. In particular we highlight the methods we have applied to provide efficient wavelength separation of the VUV radiation from the longer wavelength components used to generate it and discuss a number of systems that we have studied with the instrument which highlight its flexibility for use in the study of molecular spectroscopy. PMID- 22299970 TI - A comparison of light spot hydrophone and fiber optic probe hydrophone for lithotripter field characterization. AB - The performance of a newly developed light spot hydrophone (LSHD) in lithotripter field characterization was compared to that of the fiber optic probe hydrophone (FOPH). Pressure waveforms produced by a stable electromagnetic shock wave source were measured by the LSHD and FOPH under identical experimental conditions. In the low energy regime, focus and field acoustic parameters matched well between the two hydrophones. At clinically relevant high energy settings for shock wave lithotripsy, the measured leading compressive pressure waveforms matched closely with each other. However, the LSHD recorded slightly larger |P_| (p < 0.05) and secondary peak compressive pressures (p < 0.01) than the FOPH, leading to about 20% increase in total acoustic pulse energy calculated in a 6 mm radius around the focus (p = 0.06). Tensile pulse durations deviated ~5% (p < 0.01) due to tensile wave shortening from cavitation activity using the LSHD. Intermittent compression spikes and laser light reflection artifacts have been correlated to bubble activity based on simultaneous high-speed imaging analysis. Altogether, both hydrophones are adequate for lithotripter field characterization as specified by the international standard IEC 61846. PMID- 22299971 TI - Creating a high temperature environment at high pressure in a gas piston cylinder apparatus. AB - An internal heater capable of 1400 K has been developed for use with a gas piston cylinder apparatus capable of achieving in excess of 3 GPa with an argon pressure medium. The heated gas piston cylinder produces a truly hydrostatic environment for samples up to 3 mm in diameter and 8 mm in length. The apparatus can be used to study systems that are sensitive to stress or samples that cannot withstand shear tractions. The gas piston cylinder apparatus was developed in an effort to reduce experimental uncertainty in the pressure scale and has been used to improve understanding of the Bi I-II transition at 298 K. We estimate that the pressure during a high temperature soak in the gas piston cylinder can be known to within +/-0.01 GPa. PMID- 22299972 TI - Omni-directional selective shielding material based on amorphous glass coated microwires. AB - The shielding effectiveness of the omni-directional selective shielding material based on CoFe-glass coated amorphous wires in 0.8 GHz-3 GHz microwave frequency range is investigated. The measurements were done in a controlled medium using a TEM cell and in the free space using horn antennas, respectively. Experimental results indicate that the composite shielding material can be developed with desired shielding effectiveness and selective absorption of the microwave frequency range by controlling the number of the layers and the length of microwires. PMID- 22299973 TI - Angular measurement of acoustic reflection coefficients by the inversion of V(z, t) data with high frequency time-resolved acoustic microscopy. AB - For inspection of mechanical properties and integrity of critical components such as integrated circuits or composite materials by acoustic methodology, it is imperative to evaluate their acoustic reflection coefficients, which are in close correlation with the elastic properties, thickness, density, and attenuation and interface adhesion of these layered structures. An experimental method based on angular spectrum to evaluate the acoustic coefficient as a function of the incident angle, theta, and frequency, omega, is presented with high frequency time-resolved acoustic microscopy. In order to achieve a high spatial resolution for evaluation of thin plates with thicknesses about one or two wavelengths, a point focusing transducer with a nominal center frequency of 25 MHz is adopted. By measuring the V(z, t) data in pulse mode, the reflection coefficient, R(theta, omega), can be reconstructed from its two-dimensional spectrum. It brings simplicity to experimental setup and measurement procedure since only single translation of the transducer in the vertical direction is competent for incident angle and frequency acquisition. It overcomes the disadvantages of the conventional methods requiring the spectroscopy for frequency scanning and/or ultrasonic goniometer for angular scanning. Two substrates of aluminum and Plexiglas and four stainless plates with various thicknesses of 100 MUm, 150 MUm, 200 MUm, and 250 MUm were applied. The acoustic reflection coefficients are consistent with the corresponding theoretical calculations. It opened the way of non-destructive methodology to evaluate the elastic and geometrical properties of very thin multi-layers structures simultaneously. PMID- 22299974 TI - A contactless methodology of picking up micro-particles from rigid surfaces by acoustic radiation force. AB - Controlled movement and pick up of small object from a rigid surface is a primary challenge in many applications. In this paper, a contactless methodology of picking up micro-particles within deionized water from rigid surfaces by acoustic radiation force is presented. In order to achieve this, an acoustic radiation force was generated by 1.75 MHz transducers. A custom built setup facilitates the optimization of the sound field by varying the parameters such as sound source size and source position. The three-dimensional pressure distributions are measured and its relative sound field is also characterized accordingly. The standing wave field has been formed and it is mainly composed of two obliquely incident plane waves and their reflectors. We demonstrated the gripping and positioning of silica beads, SiO(2), and aluminum micro-particles of 100 MUm to 500 MUm in size with this method using acoustic radiation force. The acoustic radiation force generated is well controlled, contactless, and in the tens of nano-Newton range which allowed us to manipulate relative big micro objects such as MEMS components as well as moving objects such as living cells. The proposed method provided an alternative form of contactless operating environment with scalable dimensions suitable for the manipulating of small objects. This permits high-throughput processing and reduction in time required for MEMS assembling, cell biomechanics, and biotechnology applications. PMID- 22299975 TI - Overcoming the influence of the coupling fluid in photopyroelectric measurements of solid samples. AB - The thermal diffusivity of solid samples is systematically underestimated in a photopyroelectric technique used in the standard back configuration due to the presence of the coupling fluid between sample and detector. In this work, we propose a new method to overcome the undesired effect of the coupling fluid. It relies on the use of a transparent pyroelectric sensor and a transparent coupling fluid, together with a self-normalization procedure. In this way, we are able to measure accurately (a) the thermal diffusivity of opaque solid samples, and (b) the thermal diffusivity and the optical absorption coefficient of semitransparent solid samples. PMID- 22299976 TI - Multiple pulse-heating experiments with different current to determine total emissivity, heat capacity, and electrical resistivity of electrically conductive materials at high temperatures. AB - A modified pulse-heating method is proposed to improve the accuracy of measurement of the hemispherical total emissivity, specific heat capacity, and electrical resistivity of electrically conductive materials at high temperatures. The proposed method is based on the analysis of a series of rapid resistive self heating experiments on a sample heated at different temperature rates. The method is used to measure the three properties of the IG-110 grade of isotropic graphite at temperatures from 850 to 1800 K. The problem of the extrinsic heating-rate effect, which reduces the accuracy of the measurements, is successfully mitigated by compensating for the generally neglected experimental error associated with the electrical measurands (current and voltage). The results obtained by the proposed method can be validated by the linearity of measured quantities used in the property determinations. The results are in reasonably good agreement with previously published data, which demonstrate the suitability of the proposed method, in particular, to the resistivity and total emissivity measurements. An interesting result is the existence of a minimum in the emissivity of the isotropic graphite at around 1120 K, consistent with the electrical resistivity results. PMID- 22299977 TI - Influence of piezoceramic to fused silica plate thickness on the radii of curvature of piezoelectric bimorph mirror. AB - Piezoelectric based bimorph mirrors (PBM) find extensive use in focusing of x-ray beams. Many optical instruments require use of PBM whose radii of curvature can be tuned precisely. The 100 mm and 300 mm PBMs were fabricated with varying piezoelectric to fused silica plate thicknesses. The radii of curvature of free standing mirrors were measured as a function of voltage and it was found to decrease with increasing voltage. For a given piezoelectric plate thickness, as the fused silica thickness increases, the radii of curvature was found to increase owing to increase in stiffness of the mirror. On the other hand, for a given fused silica plate thickness, when the piezoelectric plate thickness is increased, the radii of curvature are decreased for a given electric field, due to increase in generated force. This study brings out the influence of piezoceramic to fused silica plate thickness on the radii of curvature of PBM. PMID- 22299978 TI - Fast on-wafer electrical, mechanical, and electromechanical characterization of piezoresistive cantilever force sensors. AB - Validation of a technological process requires an intensive characterization of the performance of the resulting devices, circuits, or systems. The technology for the fabrication of micro and nanoelectromechanical systems (MEMS and NEMS) is evolving rapidly, with new kind of device concepts for applications like sensing or harvesting are being proposed and demonstrated. However, the characterization tools and methods for these new devices are still not fully developed. Here, we present an on-wafer, highly precise, and rapid characterization method to measure the mechanical, electrical, and electromechanical properties of piezoresistive cantilevers. The setup is based on a combination of probe-card and atomic force microscopy technology, it allows accessing many devices across a wafer and it can be applied to a broad range of MEMS and NEMS. Using this setup we have characterized the performance of multiple submicron thick piezoresistive cantilever force sensors. For the best design we have obtained a force sensitivity Re(F) = 158MUV/nN, a noise of 5.8 MUV (1 Hz-1 kHz) and a minimum detectable force of 37 pN with a relative standard deviation of sigma(r) ~ 8%. This small value of sigma(r), together with a high fabrication yield >95%, validates our fabrication technology. These devices are intended to be used as bio-molecular detectors for the measurement of intermolecular forces between ligand and receptor molecule pairs. PMID- 22299979 TI - Dynamic thermomechanical response of bimaterial microcantilevers to periodic heating by infrared radiation. AB - This paper investigates the dynamic thermomechanical response of bimaterial microcantilevers to periodic heating by an infrared laser operating at a wavelenegth of 10.35 MUm. A model relates incident radiation, heat transfer, temperature distribution in the cantilever, and thermal expansion mismatch to find the cantilever displacement. Experiments were conducted on two custom fabricated bimaterial cantilevers and two commercially available bimaterial microcantilevers. The cantilever response was measured as a function of the modulation frequency of the laser over the range of 0.01-30 kHz. The model and the method of cantilever displacement calibration can be applied for bimaterial cantilever with thick coating layer. The sensitivity and signal-to-noise of bimaterial cantilevers were evaluated in terms of either total incident power or incident flux. The custom-fabricated bimaterial cantilevers showed 9X or 190X sensitivity improvement compared to commercial cantilevers. The detection limit on incident flux is as small as 0.10 pW MUm(-2) Hz(-1/2). PMID- 22299980 TI - Development of revolving drop surface tensiometer. AB - A revolving drop surface tensiometer, which measures the surface tension of a small amount of liquid, is proposed. A remarkable feature of this device is that while using the pendant drop method, it employs a centrifugal force to deform the liquid droplet. The centrifugal force induces a large distortion of the droplet, which enables an accurate measurement of the surface tension to be made. In our experimental setup, the centrifugal force can be increased so that the apparent acceleration becomes up to 100 times larger than that due to gravity, and the capability of this method to measure surface tensions was demonstrated with ethylene glycol. PMID- 22299981 TI - Insulated gold scanning tunneling microscopy probes for recognition tunneling in an aqueous environment. AB - Chemically functionalized probes are required for tunneling measurements made via chemical contacts ("Recognition Tunneling"). Here, we describe the etching of gold STM probes suitable for chemical functionalization with moieties bearing thiol groups. Insulated with high density polyethylene, these probes may be used in aqueous electrolytes with sub pA leakage currents. The area of the exposed probe surface was characterized via the saturation current in an electroactive solution (0.1 M K(3)Fe(CN)(6)). Twenty five percent of the probes had an exposed region of 10 nm radius or less. PMID- 22299982 TI - Nondestructive identification of isotopes using nuclear resonance fluorescence. AB - Nondestructive identification of heavy isotopes concealed in a thick iron box has been demonstrated by using nuclear resonance fluorescence. A quasi-monochromatic photon beam produced by the collision of laser quanta with high energy electrons was used for resonant excitation of nuclear levels in (206)Pb and (208)Pb. By measuring the resonant gamma rays emitted from (206)Pb and (208)Pb, each of these isotopes were clearly identified. The ratio of the effective thickness, i.e., concentration distribution, of these isotopes was deduced from the relative intensities of the measured nuclear resonance fluorescence strengths. PMID- 22299983 TI - Four degree of freedom liquid dispenser for direct write capillary self-assembly with sub-nanoliter precision. AB - Capillary forces provide a ubiquitous means of organizing micro- and nanoscale structures on substrates. In order to investigate the mechanism of capillary self assembly and to fabricate complex ordered structures, precise control of the meniscus shape is needed. We present a precision instrument that enables deposition of liquid droplets spanning from 2 nl to 300 MUl, in concert with mechanical manipulation of the liquid-substrate interface with four degrees of freedom. The substrate has sub-100 nm positioning resolution in three axes of translation, and its temperature is controlled using thermoelectric modules. The capillary tip can rotate about the vertical axis while simultaneously dispensing liquid onto the substrate. Liquid is displaced using a custom bidirectional diaphragm pump, in which an elastic membrane is hydraulically actuated by a stainless steel syringe. The syringe is driven by a piezoelectric actuator, enabling nanoliter volume and rate control. A quantitative model of the liquid dispenser is verified experimentally, and suggests that compressibility in the hydraulic line deamplifies the syringe stroke, enabling sub-nanoliter resolution control of liquid displacement at the capillary tip. We use this system to contact-print water and oil droplets by mechanical manipulation of a liquid bridge between the capillary and the substrate. Finally, we study the effect of droplet volume and substrate temperature on the evaporative self-assembly of monodisperse polymer microspheres from sessile droplets, and demonstrate the formation of 3D chiral assemblies of micro-rods by rotation of the capillary tip during evaporative assembly. PMID- 22299984 TI - A torsion balance for impulse and thrust measurements of micro-Newton thrusters. AB - This paper reports the performance of a torsion-type thrust stand suitable for studies of micro-Newton thrusters, which is developed for ground testing the micro-Newton thruster in Chinese Test of the Equivalence Principle with Optical readout space mission. By virtue of specially suspending design and precise assembly of torsion balance configuration, the thrust stand with load capacity up to several kilograms is able to measure the impulse bit up to 1350 MUNs with a resolution of 0.47 MUNs, and the average thrust up to 264 MUN with a resolution of 0.09 MUN in both open and close loop operation. A pulsed plasma thruster, the preliminary prototype developed for Chinese TEPO space mission, is tested by the thrust stand, and the results reveal that the average impulse bit per pulse is measured to be 58.4 MUNs with a repeatability of about 5%. PMID- 22299985 TI - High pressure rheometer for in situ formation and characterization of methane hydrates. AB - We present a novel setup for a high pressure rheometer operating with concentric cylinders geometry for in situ studies of hydrate formation and rheological characterization. The apparatus uses an external high pressure mixing cell to saturate water-in-oil emulsions with methane gas. The capability of mixing combined with a true rheometer design make this apparatus unique in terms of setup and sample formation. We have used the apparatus to form gas hydrates in situ from water-in-oil emulsions and characterize suspension rheological properties such as yield stress and shear-thinning behavior. PMID- 22299986 TI - Continual in-plane displacement measurement with temporal wavelet transform speckle pattern interferometry. AB - A heterodyne temporal speckle pattern interferometer that measures the in-plane displacement dynamically has been built. The object is displaced in its plane continuously and the frequency-modulated output signals with a carrier frequency are recorded by a CCD camera. The displacement information is extracted with wavelet transform technique. Preliminary experiments have been performed with such interferometer. The respective measurement results recovered from wavelet transform and Fourier transform are compared. PMID- 22299987 TI - Development of roll-to-roll hot embossing system with induction heater for micro fabrication. AB - In this paper, a hot embossing heating roll with induction heater inside the roll is proposed. The induction heating coil is installed inside a roll that is used as a heating roll of a roll-to-roll (R2R) hot embossing apparatus. Using an inside installed heating coil gives the roll-to-roll hot embossing system a more even temperature distribution on the surface of the heating roll compared to that of previous systems, which used an electric wire for heating. This internal induction heating roll can keep the working environment much cleaner because there is no oil leakage compared to the oiled heating roll. This paper describes the principles and provides an analysis of this proposed system; some evaluation has also been performed for the system. A real R2R hot embossing heating roll system was fabricated and some experiments on micro-pattering have been performed. After that, evaluation has been performed on the results. PMID- 22299988 TI - A new borehole wire extensometer with high accuracy and stability for observation of local geodynamic processes. AB - Very stable and reliable instruments with high accuracy are required in field measurements for continuous monitoring local geodynamic processes, such as tectonic movements, ground motions in landslide prone areas, etc. A sensitive borehole wire extensometer with low energy consumption was developed in the Geodetic and Geophysical Research Institute of the Hungarian Academy of Sciences to observe very small vertical movements (in the order of a few millimeters) of the upper layer of the soil due to hydrological, meteorological and biological processes. The newly developed instrument eliminates the disadvantages of the borehole wire extensometers which are presently used. Its sensitivity and stability are much higher than these parameters of the previous instruments. The instrument is able to measure distance variations without instrumental drift in a range of 0-4 mm with a resolution of better than 1 MUm. Since the effect of the yearly temperature variations can be easily removed from the extensometric data record, the compensation for the short-periodic (daily) thermal effects on the instrument was of high priority during the design of the instrument. This paper describes the construction and calibration of the extensometer. The extensometer was installed for monitoring vertical ground movements due to hydro meteorological processes on the high loess wall of the Danube River at Dunafoldvar, Hungary. The efficiency of the temperature compensation of the instrument was investigated in detail on the basis of the measured data series. PMID- 22299989 TI - Increased bandwidth for dielectric spectroscopy of proteins through electrode surface preparation. AB - Dielectric spectroscopy measurements of liquids are often limited by electrode polarization. The influence of surface polishing and deposition of the conducting polymer polypyrrole/polystyrenesulfonate (PPy/PSS) on the polarization impedance is investigated. A quantitative description of the electrode polarization contribution to the real-valued permittivity spectrum is derived. This description explains the origin of the omega(-const). (const.>1) dependency commonly observed in permittivity measurements. Electrode surface roughness is correlated with both the magnitude and phase of the constant phase element. Generally, rougher electrodes have better performance, and an order of magnitude bandwidth improvement is achieved using PPy/PSS electrodes. PMID- 22299990 TI - High power rapidly tunable system for laser cooling. AB - We present a laser configuration capable of fast frequency changes with a high power output and a large tuning range. The system integrates frequency tuning with an acousto-optic modulator with a double pass tapered amplifier. A compensation circuit keeps the seed power constant and prevents damage to the amplifier. A single mode fiber decouples the modulation and amplification sections and keeps the alignment fixed. The small power required to saturate the amplifier makes the system very reliable. We use the system to obtain a dipole trap that we image using a beam derived from the same configuration. PMID- 22299991 TI - Glow-to-arc transition events in H2-Ar direct current pulsed plasma: automated measurement of current and voltage. AB - The glow-to-arc transition phenomena (arcing) observed in plasma reactors used in materials processing was studied through the arcs characteristic current and voltage waveforms. In order to capture these arcs signals, a LABVIEWTM based automated instrumentation system (ARCVIEW) was developed, including the integration of an oscilloscope equipped with proper current and voltage probes. The system also allows capturing the process parameters at the arc occurrence moments, which were used to map the arcs events conditions. Experiments in H(2) Ar DC pulsed plasma returned signals data from 215 arcs events, which were analyzed through software routines. According to the results, an anti-arcing system should react in the time order of few microseconds to prevent most of the damage caused by the undesired arcing phenomena. PMID- 22299992 TI - A new quasi-steady method to measure gas permeability of weakly permeable porous media. AB - A new quasi-steady method for the determination of the apparent gas permeability of porous materials is presented in this paper along with the corresponding interpretative physical model derived from the unsteady flow equations. This method is mainly dedicated to the measurement of very low permeability of thin porous media, although thicker but more permeable samples may also be analyzed. The method relies on quasi-steady flow resulting from a (quasi) constant pressure maintained at the inlet face of the sample. Gas flow-rate, as low as 3 * 10(-10) m(3)/s, is determined from the record of pressure increase in a reservoir connected to the outlet face of the sample. An estimate of the characteristic time, t(c), to reach quasi-steady flow after imposing a constant pressure at the inlet is derived. It is validated by direct numerical simulations of the complete unsteady flow, clearly defining the required experimental duration for the method to apply. Experimental results obtained on rather permeable and thick rock samples are reported showing an excellent agreement of the measured permeability with that determined independently on the same sample whereas the experimental value of t(c) is also in very good agreement with the predicted one. The method is further employed on a composite material sheet allowing the identification of an apparent gas permeability of about 10(-23) m(2). PMID- 22299993 TI - Design and operation of the wide angular-range chopper spectrometer ARCS at the Spallation Neutron Source. AB - The wide angular-range chopper spectrometer ARCS at the Spallation Neutron Source (SNS) is optimized to provide a high neutron flux at the sample position with a large solid angle of detector coverage. The instrument incorporates modern neutron instrumentation, such as an elliptically focused neutron guide, high speed magnetic bearing choppers, and a massive array of (3)He linear position sensitive detectors. Novel features of the spectrometer include the use of a large gate valve between the sample and detector vacuum chambers and the placement of the detectors within the vacuum, both of which provide a window-free final flight path to minimize background scattering while allowing rapid changing of the sample and sample environment equipment. ARCS views the SNS decoupled ambient temperature water moderator, using neutrons with incident energy typically in the range from 15 to 1500 meV. This range, coupled with the large detector coverage, allows a wide variety of studies of excitations in condensed matter, such as lattice dynamics and magnetism, in both powder and single-crystal samples. Comparisons of early results to both analytical and Monte Carlo simulation of the instrument performance demonstrate that the instrument is operating as expected and its neutronic performance is understood. ARCS is currently in the SNS user program and continues to improve its scientific productivity by incorporating new instrumentation to increase the range of science covered and improve its effectiveness in data collection. PMID- 22299994 TI - Design and application of a new series of gallbladder endoscopes that facilitate gallstone removal without gallbladder excision. AB - In recent years, some Chinese doctors have proposed a new concept, gallstone removal without gallbladder excision, along with transition of the medical model. As there is no specialized endoscope for gallstone removal without gallbladder excision, we designed and produced a new series of gallbladder endoscopes and accessories that have already been given a Chinese invention patent (No. ZL200810199041.2). The design of these gallbladder endoscopes was based on the anatomy and physiology of the gallbladder, characteristics of gallbladder disease, ergonomics, and industrial design. This series of gallbladder endoscopes underwent clinical trials in two hospitals appointed by the State Administration of Traditional Chinese Medicine. The clinical trials showed that surgeries of gallstones, gallbladder polyps, and cystic duct calculus could be smoothly performed with these products. In summary, this series of gallbladder endoscopes is safe, reliable, and effective for gallstone removal without gallbladder excision. This note comprehensively introduces the research and design of this series of gallbladder endoscopes. PMID- 22299995 TI - A tapered undulator experiment at the ELBE far infrared hybrid-resonator oscillator free electron laser. AB - A tapered undulator experiment was carried out at the ELBE far-infrared free electron laser (FEL). The oscillator FEL makes use of a hybrid optical resonator. The main motivation was to see whether the presence of a dispersive medium in the form of a waveguide in the resonator has any effect on the outcome. The FEL saturated power and the wavelength shifts have been measured as a function of both positive as well as negative undulator field amplitude tapering. In contrast to the typical high-gain FELs where positive tapering proves beneficial for the output power we observed an improvement of performance at negative taper. During the same experiments we studied the characteristics of the detuning curves. The width of the curves indicates a maximum small signal gain for zero taper while the output peak power increases with negative taper. The saturated power output, the detuning curve characteristics, and the wavelength shifts agrees with the theoretical predictions. Details of the experiment are presented. PMID- 22299996 TI - Design, construction, and calibration of an isothermal titration calorimeter and its application in the study of the adsorption of phenolic compounds. AB - An isothermal calorimetric titration was designed and built, and some of the results obtained are presented here. For this purpose, a Calvet heat-conducting microcalorimeter was developed and connected to a titration unit built for this experiment to record titration thermograms. The microcalorimeter was electrically calibrated to establish its sensitivity and reproducibility, obtaining K = 13.56 +/- 0.21 W V(-1). Additionally, the equipment was tested using the heat of neutralisation for the tris-hydroxymethyl-aminomethane-HCl (THAM-HCl) system, obtaining DeltaH = -30.92 +/- 0.03 kJ mol(-1). The unit was assembled to obtain titration heats and the corresponding thermodynamic variables (DeltaH, DeltaG, DeltaS, and K(e)) with a system of phenolic derivatives-activated carbon (synthesised from potato peel). PMID- 22299997 TI - Note: An adhesion measurement setup for bioinspired fibrillar surfaces using flat probes. AB - Current adhesion measurement setups designed for experiments on bioinspired fibrillar surfaces, either commercial or constructed in-house, do not allow adhesion measurements with in situ visualization, high resolution, high force range, and controlled alignment at the same time. In this paper a new adhesion tester is presented, which enables contact experiments with controlled tilt angle (accuracy of +/-0.02 degrees ). This allows the use of flat probes and thus greatly simplifies the determination of experimental parameters such as pull-off strength or Young's modulus. The deflection of a double-clamped glass beam is measured by laser interferometry with an accuracy of +/-60 nm, which yields a precise force measurement over three orders of magnitude force range without changing the glass beam. Contact formation and detachment events can be visualized in situ. The current adhesion tester is designed for force measurements in the range of 1 MUN to 1 N and fills the gap between macroscopic tests and atomic force microscopy measurements. PMID- 22299998 TI - Note: Piezoelectric polymers as transducers for the ultrasonic-reflection method and the application in mechanical property-screening of coatings. AB - In the last years, non-destructive ultrasonic testing methods are more and more frequently employed in order to investigate the drying and curing processes of different coatings. Among them an ultrasonic reflection method was developed allowing the simultaneous measurement with longitudinal and transversal waves. In order to generate the ultrasonic pulse, piezoelectric ceramics or oxides are usually used as transducer materials which are connected to a delay line. Here, we demonstrate a similar approach for the ultrasonic reflection method installing piezoelectric polymers as ultrasonic transducer materials. In detail, poly(vinylidene fluoride and trifluoroethylene) [P(VDF-TrFE)] copolymers were prepared as piezoelectric transducer layers directly onto the metallization of glass delay lines avoiding additional bonding processes. The film preparation was carried out by solvent casting the polymer onto an area with a diameter of 12 mm and is optimized so that relatively homogeneous polymer layers with thicknesses between 14 and 35 MUm are adjusted by the deposited amount of the polymer. Electrical poling renders the polymer piezoelectric. The ultrasonic properties of the P(VDF-TrFE) transducer and their usability for the ultrasonic reflection method are described also in comparison to previous measurements using LiNbO(3) transducer. PMID- 22299999 TI - Note: Thermal conductivity measurement of individual poly(ether ketone)/carbon nanotube fibers using a steady-state dc thermal bridge method. AB - Customized engineered fibers are currently being used extensively in the aerospace and automobile industries due to the ability to "design in" specific engineering characteristics. Understanding the thermal conductivity of these new fibers is critical for thermal management and design optimization. In the current investigation, a steady-state dc thermal bridge method (DCTBM) is developed to measure the thermal conductivity of individual poly(ether ketone) (PEK)/carbon nanotube (CNT) fibers. For non-conductive fibers, a thin platinum layer was deposited on the test articles to serve as the heater and temperature sensor. The effect of the platinum layer on the thermal conductivity is presented and discussed. DCTBM is first validated using gold and platinum wires (25 MUm in diameter) over a temperature ranging from room temperature to 400 K with +/-11% uncertainty, and then applied to PEK/CNT fibers with diverse CNT loadings. At a 28 wt. % CNT loading, the thermal conductivity of fibers at 390 K is over 27 Wm( 1)K(-1), which is comparable to some engineering alloys. PMID- 22300000 TI - Note: Voltage and intensity dependence of the saturation curves of free-air ionization chambers irradiated with chopped synchrotron radiation beams. AB - Current saturation characteristics of free-air ionization chambers with electrode gaps of 4.2 and 8.4 mm were investigated using pulsed photon beam obtained by periodically interrupting synchrotron radiation beams with a chopper. Pulsed photon beams of 10 and 15 keV with pulse duration of 2.5 MUs and a frequency of 230 Hz were produced by chopping the beam. The measured recombination rate was found to be proportional to the intensity and inversely proportional to the applied voltage. PMID- 22300001 TI - Note: Phase sensitive detection of photoluminescence with Fourier transform spectroscopy. AB - Although known for more than twenty years, there is limited information in the literature regarding the experimental parameters of lock-in based phase sensitive emission detection in conjunction with Fourier spectrometers. For this technique also known as double modulation spectroscopy - we present a guideline for parameter optimization by measuring the photoluminescence of InSb:Te at cryogenic temperatures. PMID- 22300002 TI - Note: Development of target changeable palm-top pyroelectric x-ray tube. AB - A target changeable palm-top size x-ray tube was realized using pyroelectric crystal and detachable vacuum flanges. The target metals can be exchanged easily by attaching them on the brass stage with carbon tape. When silver and titanium palates (area: 10 mm(2)) were used as targets, silver Lalpha and titanium K lines were clearly observed by bombarding electrons on the targets for 90 s. The intensities were the same or higher than those of previously reported pyroelectric x-ray tubes. Chromium, iron, nickel, copper, and zinc K lines in the x-ray tube (stainless steel and brass) disappeared by replacing the brass stage and the stainless steel vacuum flange with a carbon stage and a glass tube, respectively. PMID- 22300003 TI - Note: Bending compliances of generalized symmetric notch flexure hinges. AB - The bending compliances of generalized notch flexure hinges with transverse or transverse-and-axial symmetry are studied in two particular reference frames. For an end-point reference frame, the cross compliance and the rotary compliance are proportional. When the reference frame is placed at the flexure's midpoint, the cross compliance is zero. The translatory and rotary compliances of only half the flexure hinge are sufficient to calculate the overall compliances of a transverse symmetry flexure configuration. Similarly, the overall bending compliances of a flexure hinge with transverse-and-axial symmetry require prior calculation of the translatory and rotary compliances of a quarter flexure solely. PMID- 22300005 TI - Effect of social capital and personal autonomy on the incidence of depressive symptoms in the elderly: evidence from a longitudinal study in Mexico. AB - OBJECTIVES: To estimate the effect of social capital (SC) and personal autonomy (PA) on the depressive symptoms (DS) in older people living in poverty. METHOD: Longitudinal study of elderly participants in the impact evaluation study of a non-contributory pension program in Mexico. For this study we selected the group of older people without significant DS at baseline. PA, SC indicators and covariates were measured at baseline. Using the Geriatric Depression Scale, the incidence of DS was assessed at a follow-up interview after 11 months. The effect of SC and autonomy on the occurrence of DS was estimated by using a multilevel logistic regression model. RESULTS: Of the various indicators of PA, not being dependent in daily functioning, and being able to read/write were associated with lower risk of DS. A higher level of SC at baseline was associated with lower incidence of DS in women (odds ratio; OR = 0.73, p < 0.01), while for men there was no significant association (OR = 1.04, p = 0.69). CONCLUSIONS: PA and SC proved to be protective factors against the onset of DS in women. For men, only PA was a protective factor. Future studies need to explore in what ways that PA and SC may reduce risk of DS as well as the role of gender differences. PMID- 22300006 TI - Extensive bilateral leg ulceration. PMID- 22300007 TI - The cholecystokinin CCK2 receptor antagonist, JNJ-26070109, inhibits gastric acid secretion and prevents omeprazole-induced acid rebound in the rat. AB - BACKGROUND AND PURPOSE: JNJ-26070109 [(R)4-bromo-N-[1-(2,4-difluoro-phenyl) ethyl]-2-(quinoxaline-5-sulfonylamino)-benzamide] is a novel antagonist at cholecystokinin CCK(2) receptors with good pharmacokinetic properties and represents a novel mechanism for the treatment of gastro-oesophageal reflux disease (GORD). The purpose of the present study was to determine whether chronic treatment with JNJ-26070109 could prevent, as well as treat, acid rebound in rats. EXPERIMENTAL APPROACH: A chronic fistula was surgically inserted into the stomach of rats to enable the measurement of acid secretion under basal, pentagastrin and histamine-stimulated conditions. JNJ-26070109 and omeprazole were administered separately and in combination. KEY RESULTS: Sustained administration of omeprazole alone and in combination with JNJ-26070109 inhibited gastric acid secretion by >90%. However, 3 days after withdrawing treatment, there was a rebound hypersecretion by ~1.5-fold in omeprazole-treated animals. No such acid rebound was observed with JNJ-26070109 alone or with co-administration of JNJ-26070109 and omeprazole. The anti-trophic effects of JNJ-26070109 in the gastric mucosal paralleled the effects on acid rebound. Administration of JNJ 26070109 for 3 days after cessation of omeprazole prevented the occurrence of acid rebound. Interestingly, chronic, but not acute, treatment with JNJ-26070109 also inhibited histamine-stimulated acid secretion. CONCLUSIONS AND IMPLICATIONS: Chronic administration of JNJ-26070109 effectively inhibited gastric acid secretion and suppressed proton pump inhibitor (PPI)-induced acid rebound in the rat. This work advances the field by demonstrating that modest doses of a competitive CCK(2) receptor antagonist have significant and functionally important anti-trophic actions in the gastric mucosa. These properties make JNJ 26070109 a suitable candidate for clinical investigation for the treatment of GORD. PMID- 22300008 TI - PHANTOM-S: the prehospital acute neurological therapy and optimization of medical care in stroke patients - study. AB - RATIONALE: Time from symptom onset to treatment is closely associated with the effectiveness of intravenous thrombolysis in acute ischemic stroke patients. Hospitals are encouraged to take every effort to shorten delay of treatment. Despite combined efforts to streamline procedures in hospitals to provide treatment as soon as possible, most patients receive tissue plasminogen activator with considerable delay and very few of them within 90 mins. Germany has an internationally acknowledged prehospital emergency care system with specially trained doctors on ambulances. We developed an ambulance equipped with a Computed Tomography (CT) scanner, point-of-care laboratory, teleradiological support, and an emergency-trained neurologist on board. In the Pre-Hospital Acute Neurological Therapy and Optimization of Medical care in Stroke Patients study, we aim at a reduction of the current alarm-to-needle time by prehospital use of tissue plasminogen activator in an ambulance. AIMS: We hypothesized that compared with regular care, we will reduce alarm-to-needle time by a minimum of 20 mins by implementation of the stroke emergency mobile unit. DESIGN: Prospective study comparing randomly allocated periods with and without stroke emergency mobile unit availability. STUDY OUTCOMES: Primary end point of the study is alarm-to needle time. Secondary outcomes include thrombolysis treatment rates, modified Rankin scale after three-months, and alarm-to-imaging or alarm-to-laboratory time; safety aspects to be evaluated are mortality and rates of (symptomatic) intracerebral hemorrhage. PMID- 22300010 TI - Structures of the amyloid beta-peptides Abeta1-40 and Abeta1-42 as influenced by pH and a D-peptide. AB - In this simulation study, we present a comparison of the secondary structure of the two major alloforms of the Alzheimer's peptide (Abeta(1-40) and Abeta(1-42)) on the basis of molecular dynamics (MD) simulations on thea microsecond time scale using the two GROMOS96 force fields ffG43a2 and ffG53a6. We observe peptide and force-field related differences in the sampled conformations of Abeta(1-40) and Abeta(1-42), which we characterize in terms of NMR chemical shifts calculated from the MD trajectories and validate against the corresponding experimental NMR results. From this analysis, we can conclude that ffG53a6 is better able to model the structural propensities of Abeta(1-40) and Abeta(1-42) than ffG43a2. Furthermore, we provide a description of the influences of pH and binding of D3, a 12-residue D-enantiomeric peptide with demonstrated antiamyloid effects, on the structure of Abeta(1-42). We demonstrate that, under slightly acidic conditions, protonation of the three histidine residues in Abeta(1-42) promotes the formation of beta-sheets via a reduction in electrostatic repulsion between the two terminal regions. Our studies further reveal that the binding between D3 and Abeta(1-42) is driven by electrostatic interactions between negatively charged Abeta(1-42) residues and the five positively charged arginine residues of D3. The binding of D3 was found to induce large conformational changes in the amyloid peptide, with a reduction in beta-sheet units being the most significant effect recorded, possibly explaining the observed amyloid-inhibiting properties of the D peptide. PMID- 22300011 TI - Intravitreal aflibercept injection for neovascular (wet) age-related macular degeneration. AB - INTRODUCTION: Age-related macular degeneration (AMD) continues to be a leading cause of blindness worldwide. The neovascular form of the disease can lead to rapid and progressive vision loss. Vascular endothelial growth factor (VEGF) has emerged as a key target of treatment, with inhibitors of VEGF being shown to arrest the angiogenic process and avoid the visual damage typically associated with its presence. AREAS COVERED: This manuscript reviews the treatment history for wet AMD and examines aflibercept , a new, fully human, recombinant fusion protein designed to bind all isoforms of VEGF-A, as well as placental growth factor (PGF), thereby inhibiting the binding and activation of VEGF receptors. EXPERT OPINION: The results of Phase I, II and III studies have proven aflibercept to be a safe and effective treatment for wet AMD. Recent results of Phase III studies demonstrate the efficacy of aflibercept, dosed every 8 weeks after three initial monthly doses, and show that this regimen is clinically equivalent to monthly ranibizumab therapy. EyleaTM (aflibercept) was approved by the FDA for the treatment of wet AMD on 18 November 2011. PMID- 22300012 TI - Effect of pH and light on aggregation and conformation of an IgG1 mAb. AB - During the purification process, monoclonal antibodies may be exposed to parts of UV-C (200 to 290 nm), UV-B (290 to 320 nm) and visible light (400 to 760 nm) under a variety of buffer and pH conditions. Together, these conditions can promote both chemical and physical degradation which may result in conformational changes. To examine this possibility, an IgG1 mAb at pH 3.5, 5, and 8 was exposed to UV light at multiple protein concentrations. Exposure to 302 nm light resulted in a pH-dependent formation of high molecular weight species where the degree of oligomerization increased with increasing pH. Characterization by SDS-PAGE under reducing and nonreducing conditions and size exclusion MALS revealed that the predominant species were nonreducible dimeric, trimeric and higher order oligomeric species which occurred through processes other than intermolecular disulfide bond formation. Biophysical characterization by differential scanning calorimetry demonstrated an overall loss of heat capacity suggesting a loss of conformational integrity with light exposure. A decrease in tryptophan fluorescence was paralleled by a significant decrease in the transition temperature measured during heat-induced unfolding following light exposure, also suggesting a significant change in conformational integrity. The observations by fluorescence spectroscopy coincided with pH-dependent changes in the alterations of secondary structure characterized by Fourier transform infrared spectroscopy and far-UV circular dichroism with the most acidic pH showing the greatest degree of change in the beta-sheet structure. Exposure to UV light resulted in aggregation with pH-dependent yields decreasing in the order 8.0 > 5.0 > 3.5, while the opposite trend was observed for conformational changes, with pH dependent extents decreasing in the following order 3.5 > 5.0 > 8.0. These pH dependent trends suggest that different strategies will be required to stabilize the protein against these modifications during processing. PMID- 22300013 TI - Effects of once weekly dual-task training in older adults: a pilot randomized controlled trial. AB - AIM: To compare single-task and dual-task training on obstacle avoidance, gait speed and balance in healthy community-dwelling older adults. METHODS: A total of 17 older adults (65-83 years) participated in a group circuit class, once weekly for 45 min for 4 weeks. The dual-task group carried out cognitive activities simultaneously with gait and balance exercises. The single-task training group carried out identical gait and balance activities without cognitive tasks. We assessed time to complete a 6-m obstacle course under single-task and three different dual-task conditions (spontaneous speech, alphabet recitation and coin transfer), 25-ft gait speed, Timed Up and Go, and the Activities-specific Balance Confidence Scale. RESULTS: Both groups showed significant improvement in gait speed and Timed Up and Go. In addition, the proportion of participants who achieved gait speed >1.0 m/s increased in both groups. There were no within- or between-subjects differences in obstacle course performance under single or dual task conditions after the intervention. CONCLUSION: Once weekly group circuit training focusing on balance, gait and agility, with or without simultaneous cognitive tasks, resulted in significantly improved walking speed among older adults. Group-format dual-task training once per week did not improve walking time or dual-task cost on an obstacle negotiation task. PMID- 22300014 TI - Early olfactory experience induces structural changes in the primary olfactory center of an insect brain. AB - The antennal lobe (AL) is the first olfactory center of the insect brain and is constituted of different functional units, the glomeruli. In the AL, odors are coded as spatiotemporal patterns of glomerular activity. In honeybees, olfactory learning during early adulthood modifies neural activity in the AL on a long-term scale and also enhances later memory retention. By means of behavioral experiments, we first verified that olfactory learning between the fifth and eighth day of adulthood induces better retention performances at a late adult stage than the same experience acquired before or after this period. We checked that the specificity of memory for the odorants used was improved. We then studied whether such early olfactory learning also induces long-term structural changes in the AL consistent with the formation of long-term olfactory memories. We also measured the volume of 15 identified glomeruli in the ALs of 17-day-old honeybees that either experienced an odor associated with sucrose solution between the fifth and eighth day of adulthood or were left untreated. We found that early olfactory experience induces glomerulus-selective increases in volume that were specific to the learned odor. By comparing our volumetric measures with calcium-imaging recordings from a previous study, performed in 17-day-old bees subjected to the same treatment and experimental conditions, we found that glomeruli that showed structural changes after early learning were those that exhibited a significant increase in neural activity. Our results make evident a correlation between structural and functional changes in the AL following early olfactory learning. PMID- 22300015 TI - Duodenal lipid-induced symptom generation in gastroesophageal reflux disease: role of apolipoprotein A-IV and cholecystokinin. AB - BACKGROUND: Duodenal lipid intensifies the perception of esophageal acid perfusion. Recently, we showed that genes implicated in lipid absorption were upregulated in the duodenum of fasting gastro-esophageal reflux disease (GERD) patients. This suggests that chylomicron production and secretion may be enhanced and, consequently, the release of apolipoprotein A-IV (apoA-IV), a chylomicron derived signaling protein. ApoA-IV may stimulate release of cholecystokinin (CCK), an activator of vagal afferents. This study evaluated putative involvement of abnormal apoA-IV and CCK responses to lipid in GERD. METHODS: Ten GERD patients and 10 healthy volunteers (HV) underwent duodenal perfusion with Intralipid 20%, 2 kcal min(-1) , for 60 min. Symptoms were scored, blood samples collected every 15 min during lipid perfusion and 15 min after discontinuation when duodenal biopsies were taken. Plasma and mucosal concentrations of apoA-IV and CCK and transcript levels of 21 genes implicated in lipid absorption, differentially expressed under fasting conditions, were quantified. KEY RESULTS: Heartburn (P = 0.003), abdominal discomfort (P = 0.037) and nausea (P = 0.008) only increased significantly during lipid infusion in GERD patients. Following lipid infusion mean mucosal apoA-IV concentration was lower in GERD patients compared with HV (P = 0.023), whereas plasma concentration tended to be elevated (P = 0.068). Mean mucosal CCK concentration was also lower in GERD patients (P = 0.009). Two genes, HIBADH and JTB, were upregulated in GERD patients (P = 0.008 and P = 0.038, respectively). CONCLUSIONS & INFERENCES: Our results suggest excessive duodenal lipid-induced release of apoA-IV and CCK in GERD. We postulate that the resulting heightened activation of duodenal vagal afferents may underlie central sensitization, thereby increasing the perception of reflux events. PMID- 22300016 TI - Cubic form of Pb(2-x)Sn(x)S2 stabilized through size reduction to the nanoscale. AB - We demonstrate the synthesis of semiconductor Pb(2-x)Sn(x)S(2) nanocrystals with a cubic rock salt crystal structure in a composition range where this structure is unstable in the bulk. The cubic Pb(2-x)Sn(x)S(2) nanocrystals were prepared using a modified hot injection colloidal synthetic route. The x value is in the range 0.40 < x < 1. Even though these compositions lie in a region of the PbS-SnS phase diagram where no single phase exists, and despite the fact that PbSnS(2) is a distorted orthorhombic phase, the Pb(2-x)Sn(x)S(2) nanocrystals are single phase solid solutions with cubic NaCl-type structure. Experimental evidence for this derives from powder X-ray diffraction (PXRD), electron diffraction, and pair distribution function (PDF) analysis. Elemental compositions determined using scanning transmission electron microscopy/energy dispersive spectroscopy (STEM/EDS), inductively coupled plasma-atomic emission spectroscopy (ICP-AES), and electron energy loss spectroscopy (EELS) reveal a composition close to the nominal ones. The band gaps of the Pb(2-x)Sn(x)S(2) nanocrystals (0.52-0.57 eV) are blue-shifted by quantum confinement relative to that of the hypothetical cubic PbSnS(2) phase which density functional theory (DFT) calculations show to be much narrower (0.2 eV) than in the case of orthorhombic PbSnS(2) (1.1 eV). The Pb(2-x)Sn(x)S(2) nanocrystals exhibit a well-defined band gap in the near-IR region and are stable up to ~300 degrees C above which they phase separate into cubic PbS and orthorhombic alpha-SnS. PMID- 22300017 TI - Multivisceral ex vivo surgery for tumors involving celiac and superior mesenteric arteries. AB - Abdominal tumors involving both roots of the celiac and superior mesenteric artery are deemed unresectable by conventional surgical methods. We performed three cases of multivisceral ex vivo surgery involving temporary removal of the entire abdominal viscera followed by vascular reconstruction, ex vivo tumor resection and autotransplantation of excised organs. We achieved a complete tumor resection with negative margins in all cases. All patients have survived with no tumor recurrence to date at 17-, 27- and 38-month follow-up. Postoperative complications included diarrhea, sphincter of Oddi dysfunction and arterial stenosis; all responded to directed treatments. Multivisceral ex vivo surgery applying techniques of deceased donor multivisceral transplantation is feasible in achieving local control of otherwise unresectable abdominal tumors. This surgery is best suitable for locally invasive tumors unresectable because of location and vascular involvement. PMID- 22300018 TI - Editorial: cytochromes P450: flexibility and plasticity - properties determining substrate preferences. PMID- 22300019 TI - Interplay of beta-catenin with xenobiotic-sensing receptors and its role in glutathione S-transferase expression. AB - The Wnt/beta-catenin pathway plays an important role in liver homeostasis, as well as during prenatal liver development, liver regeneration, and hepatocarcinogenesis. The connection of hepatic beta-catenin activation and expression of drug-metabolizing enzymes has been established in the past few years: on the whole, a generally positive-regulatory effect of beta-catenin on the expression and inducibility of many enzymes involved in phase I and phase II of drug metabolism has been described by different groups. The mechanisms underlying these processes are still not fully understood. However, there is accumulating evidence for a complex interaction of beta-catenin with different xenobiotic-sensing receptors, which act as transcription factors after ligand activation, for example the aryl hydrocarbon receptor or the constitutive androstane receptor. Among others, these crosstalk mechanisms might explain the manifold effects of beta-catenin on hepatic drug metabolism. In this review, the current knowledge regarding the role of Wnt/beta-catenin signaling in the regulation of hepatic expression of glutathione S-transferases is presented. In addition, the crosstalk of beta-catenin signaling with nuclear receptors involved in the regulation of glutathione S-transferases will be discussed. PMID- 22300020 TI - Liver-based in vitro technologies for drug biotransformation studies - a review. AB - Early understanding of the metabolic pathway and potential interaction of new drug candidates with other drugs is one of the goals of preclinical studies in the drug discovery process. Although other body organs are involved in drug biotransformation, the liver is the predominant organ of metabolism for a wide range of endogenous compounds and xenobiotics. The set of enzymes contained in the cytochrome P450 superfamily present predominantly in the liver have been identified as the single most important agent of drug metabolism and have formed the bedrock of most matured technologies for in vitro drug biotransformation studies. With the development of a number of liver-based technologies, in vitro metabolism has gained significant popularity in the past three decades. This has come in response to several demanding factors including the questionable relevance of data from animal studies; the high cost and stringent regulatory and ethical requirement, as well as safety issues involved with studies using human subjects; and the need for high throughput due to the wide range of chemical entities for routine investigations. These technologies which vary from whole liver to subcellular fractions have found ready application in generating the desired information on the substrate and inhibitor specificity of most metabolic enzymes. This paper reviews such technologies as isolated fresh liver; liver slices; primary, cultured and cryopreserved hepatocytes; microsomes; cytosolic fractions; and purified or heterologously expressed drug-metabolizing enzymes. It highlights the general principles of in vitro enzyme kinetics and the factors that determine the choice of each in vitro technology for biotransformation studies. PMID- 22300021 TI - An insight into the interaction between clopidogrel and proton pump inhibitors. AB - Platelet activation and aggregation have been established as pivotal elements in the pathogenesis of atherosclerotic and ischemic diseases, including acute coronary syndromes. The difficulty of achieving optimal platelet inhibition remains a major constraint following dual-antiplatelet therapy, which can lead to a diminished response following initiation of clopidogrel therapy. Though the absolute mechanisms underlying clopidogrel resistance are controversial, a variety of responsible factors are recognized. Clopidogrel, being a prodrug, requires conversion to an active metabolite for its activity. This metabolism involves various cytochrome P450 (CYP) enzymes at different steps, and it is hypothesized that competitive inhibition of CYPs may contribute to clopidogrel resistance. Proton pump inhibitors (PPIs) are competitive inhibitors of CYPs that can attenuate the antiplatelet activity of clopidogrel, and this can lead to clopidogrel resistance. Available data from different clinical studies have postulated the possibility of a drug-drug interaction between clopidogrel and PPIs. PPIs differ somewhat in their pharmacokinetic properties like bioavaibility and affinity for CYP2C19. However it is not clear whether the proposed drug interaction of PPI with clopidogrel is same with all PPIs (i.e., a class effect) or it is limited to a subset of PPIs (i.e., a drug effect). This interaction needs further assessment with well designed prospective clinical trials, before any change in clinical practice should be considered. In this review, we attempt to evaluate the available evidence exploring drug interactions with PPIs as the underlying mechanism for the reduced antiplatelet effect of clopidogrel. PMID- 22300022 TI - alpha7-Nicotinic acetylcholine receptors: an old actor for new different roles. AB - In the years from 1856 to 1936, when the Nobel Prize for Physiology/Medicine was awarded to Dale and Loewi " for their discoveries relating to chemical transmission of nerve impulses" , the nicotinic acetylcholine receptor (nAChR) emerged from an assumption to a reality. Its biochemical isolation in 1970 represents a major breakthrough in pharmacology. The alpha7-nAChR subunit forms homo-oligodimeric nAChR with unique distinctive properties, such as high permeability to calcium and modulation by the extracellular calcium concentrations, the possibility of binding two-five molecules of agonist, function modulation via phosphorylation and/or via calcium-dependent serine/threonine kinases and modulating transmitter release and activation of GABAergic interneurons. In the brain, the alpha7-nAChR plays several important functions running from synaptic plasticity, regulation of neuronal growth, differentiation and survival to enhance learning and cognition. The detection of its occurrence on non-neuronal cells raises question related to their specific activity, since in these cells it appears involved in modulation of cell death, migration and signaling. Its unbalance might involve it in different diseases such as Alzheimer, Parkinson and cancer. However, the peculiarity of alpha7-nAChR offers rational bases to develop new drugs and new therapeutic strategies. In conclusion, alpha7-nAChR roughly in 150 years of life, instead to be an old actor became an important player in regulating cell signaling. PMID- 22300023 TI - Novel approaches to study the involvement of alpha7-nAChR in human diseases. AB - The alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) is widely distributed in the human brain and has been implicated in a number of human central nervous system (CNS) diseases, including Alzheimer's and Parkinson's disease, schizophrenia and autism. Recently, new roles for alpha7 nAChRs in lung cancer and heart disease have been elucidated. Despite the importance of this receptor in human pathology, many technical difficulties are still encountered when investigating the role of alpha7 nAChRs. Electrophysiological analysis of the receptor upon heterologous expression or in human tissues was limited by the fast desensitization of alpha7-mediated nicotinic currents and by tissue availability. In addition, animal models for the human diseases related to alpha7 nAChRs have long been unavailable. The recent development of new imaging and analysis approaches such as PET and receptor microtransplantation have rendered the study of alpha7 nAChRs increasingly feasible, paving new roads to the design of therapeutic drugs. This review summarizes the current knowledge and recent findings obtained by these novel approaches. PMID- 22300024 TI - The sea urchin, Paracentrotus lividus, as a model to investigate the onset of molecules immunologically related to the alpha-7 subunit of nicotinic receptors during embryonic and larval development. AB - Nicotinic acetylcholine receptors play a major role in the regulation of electrochemical synapses at neuromuscular junctions. During the early stages of Paracentrotus lividus development, the nicotinic receptor-like molecules are found and localized by use of the specific blocker, -bungarotoxin, and by alpha-7 subunit immunoreactivity. Both the methods identify and localize the nicotinic receptor-like molecules at the sites where active changes in ionic intracellular concentration take place. These are well known to lead either fertilization, sperm propulsion or co-ordinated ciliary movement. After neural differentiation, immunoreactivity for the alpha-7 subunit is localized mainly in ganglia, ectoderm ciliary bands and in the motile cells forming the gut wall. Both alpha bungarotoxin binding sites and alpha-7 subunits are also localized at the cells linked to the skeletal rods, performing the small movements which drive the swimming direction in the water column. The localization of these molecules paves the way to a speculation on their function and possible role in neurogenesis as well as neurodegeneration. PMID- 22300025 TI - Development of radioligands for the imaging of alpha7 nicotinic acetylcholine receptors with positron emission tomography. AB - Molecular imaging of brain structures by highly sensitive non-invasive techniques offers unique possibilities in the understanding of physiological and pathological processes in the central nervous system. In particular, the quantitative analysis by positron emission tomography (PET) of alpha7 nicotinic acetylcholine receptors (alpha7 nAChR), which are involved in different signalling pathways in the brain, is assumed to provide important information on the relation between receptor dysfunction and the pathogeneses of neuropsychiatric brain diseases, but the applicability of this imaging approach is still hampered due to insufficient imaging agents. This paper presents the recent efforts made to develop PET radiotracers targeting alpha7 nAChR as well as the current state of the evaluation of the most promising radiolabelled compounds in animal models and humans. PMID- 22300026 TI - alpha7-Nicotinic receptors and cognition. AB - Nicotinic alpha7 receptors have been shown in a variety of studies with animal models to play important roles in diverse components of cognitive function, including learning, memory and attention. Mice with alpha7 receptor knockouts show impairments in memory. Selective alpha7 agonists significantly improve learning, memory and attention. alpha7 receptors in limbic structures such as the hippocampus and amygdala have been demonstrated to play critical roles in memory. Blockade of alpha7 receptors in these areas cause memory impairments. In the brains of people with schizophrenia alpha7 receptors are impaired. This may be related to pronounced cognitive impairments seen with schizophrenia. There has been a major effort to develop alpha7 nicotinic agonists for helping to reverse cognitive impairment. These receptors are a promising target for development of therapeutic treatments for a variety of diseases of cognitive impairment including Alzheimer's disease, attention deficit hyperactivity disorder (ADHD) and schizophrenia. PMID- 22300027 TI - Stress and the alpha7 nicotinic acetylcholine receptor. AB - Nicotine is well known for its deleterious effects on human health, and it has long been known that nicotine interacts with the stress axis in both man and in laboratory animals. Nicotine also has beneficial effects upon cognition, and an emerging literature has demonstrated that it may play a protective or palliative role in diseases such as Alzheimer's disease and schizophrenia. Recent advances have permitted scientists to identify the specific subtypes of nicotinic receptors responsible for the drugs varied physiological effects. The alpha7 subunit of the nicotinic acetylcholine receptor (NAchRalpha7), has been identified as a significant mediator of nicotine's interactions with the stress axis and human disease. The NAchRalpha7 has also been shown to have neuroprotective effects via multiple pathways, making it a logical target for the treatment of a number of brain disorders. PMID- 22300028 TI - alpha7 nicotinic acetylcholine receptors in Alzheimer's disease: neuroprotective, neurotrophic or both? AB - One of the early signs of Alzheimer's disease is the impairment in hippocampus based episodic memory function, which is improved through the enhancement of cholinergic transmission. Several studies suggest that alpha7 nicotinic receptor (nAChR) activation represents a useful therapeutic strategy for the cognitive impairments associated with early Alzheimer's disease as the alpha7 subtype of nicotinic acetylcholine receptors are expressed by basal forebrain cholinergic projection neurons as well as by their targets in the hippocampus. The current model for the cholinergic deficit in Alzheimer's disease posits that inappropriate accumulation of misfolded oligomeric aggregates of beta-amyloid peptide leads to the dysfunction of the signaling mechanisms that support the cholinergic phenotype; this is manifested as an altered function of nicotinic acetylcholine receptors and the nerve-growth factor trophic support system that results in the loss of cholinergic markers and eventually cholinergic neurons from the basal forebrain cholinergic system. A view was confounded by the fact that alpha7 nAChRs and beta-amyloid peptides have been shown to interact in vitro and in vivo, including human post-mortem AD brain. This review will begin with a brief overview of the basal forebrain cholinergic system, followed by a discussion of the current knowledge of the cholinergic deficit in Alzheimer's disease, then a summary of the cholinergic phenotype observed in transgenic Alzheimer's disease mouse models. We will also present our recent findings that support our hypothesis that the alpha7 nicotinic acetylcholine receptor performs both the neurotrophic and neuroprotective roles in the maintenance of the cholinergic phenotype and discusses potential mechanisms and implications for Alzheimer's disease therapy. PMID- 22300029 TI - Genetic variations in CHRNA7 or CHRFAM7 and susceptibility to dementia. AB - The presence of memory impairment and cognitive deficits in the Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and Pick's disease (PiD) has been associated to dysfunction of cholinergic transmission, possibly due to the loss of cholinergic neurons and to the elimination of nAChR in dementia patients. Alternative hypotheses take into account molecular interactions of the beta amyloid peptide Abeta with nAChR, which may lead to deregulation of the receptor function. Genetic polymorphisms of CHRNA7 and CHRFAM7A, a fusion gene containing a partial CHRNA7 duplication, have been investigated as possible susceptibility traits to dementia, potentially useful either to identify high risk individuals or as therapeutic targets. To summarize the existing evidence, a systematic re evaluation of published papers has been performed (PubMed database, no language restriction, updated to 1st August 2011). Eleven articles reporting data on genetic variations in CHRNA7 or CHRFAM7 and risk of dementia fulfilled selection criteria and were evaluated. Published evidence on the association between variations in CHRNA7 or CHRFAM7A and the risk of dementia is still sparse and inconclusive. Further studies are needed to establish whether some polymorphisms may really affect the probability of developing AD or other forms of dementia. Additional and more conclusive results may come from the ongoing GWAS studies investigating high numbers of genetic variants in large samples, that have the potential to assess the role of genetic susceptibility in dementia. PMID- 22300030 TI - alpha7 nicotinic acetylcholine receptor mediated neuroprotection in Parkinson's disease. AB - Parkinson's disease (PD) is characterized by relatively selective degeneration of dopaminergic neurons in the substantia nigra and loss of dopamine in the striatum. More than 50 epidemiological studies confirmed the low incidence of PD in smokers. Examining the distribution of subtypes of nicotinic acetylcholine receptors (nAChRs) in dopaminergic neurons of nigrostriatal system and its change in PD patients is quite important to elucidate possible neuroprotective cascade triggered by nicotine. Evidences of nAChR-mediated protection against neurotoxicity induced by rotenone, 6- hydroxydopamine (6-OHDA), and 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP) are briefly reviewed. In rotenone- and 6 OHDA-induced PD models, nAChR-mediated neuroprotection was blocked not only by alpha4beta2 but also by alpha7 nAChR antagonists. The survival signal transduction, alpha7 nAChR-Src family-PI3K-Akt/PKB cascade and subsequent upregulation of Bcl-2, would lead to neuroprotection. These findings suggest that nAChR-mediated neuroprotection is achieved through subtypes of nAChRs and common signal cascades. An early diagnosis and protective therapy with specific nAChR modulations could be effective in delaying the progression of PD. PMID- 22300031 TI - Traumatic brain injury: central and peripheral role of alpha7 nicotinic acetylcholine receptors. AB - Traumatic brain injury (TBI) is a significant public health concern worldwide for which there is no cure. Once trauma has occurred, multiple biochemical pathways are set into motion that leads to a chronic, neurodegenerative condition. Two of the most widely studied pathological pathways are excitotoxicity and inflammation, processes that are influenced by alpha7 nicotinic acetylcholine receptors (nAChR). Previous studies have found a bilateral decrease in alpha7 nAChR expression in regions of the cortex and hippocampus that occurs in relation to injury severity. Subsequent studies showed that this decrease was evident in some parts of the hippocampus as early as 1 hour post-injury and remained decreased through 21 days. Other ligand-gated ion channels, such as non-alpha7 nAChRs and n-methyl-D-aspartate (NMDA) receptors did not show a similar widespread and consistent pattern of change following TBI, nor did the G-protein coupled muscarinic acetylcholine receptors, suggesting that the alpha7 nAChR could be a key mediator in the pathophysiology of traumatic brain injury. In addition to its expression in the brain, the alpha7 nAChR has been found outside of the central nervous system (CNS) on many different cell types, including peripheral blood leukocytes, where they have a role in the cholinergic antiinflammatory pathway, and have recently been identified on platelets where they may have a role in activation. How these receptors are regulated in response to injury has not been investigated, but could potentially serve as a marker of neurodegeneration as has been done in Alzheimer's disease and schizophrenia. In this review, we will detail the role of alpha7 nAChR following TBI as well as explore the evidence of this receptor subtype in regards to blood component (leukocytes and platelets) involvement and the potential influence TBI has on peripheral expression and function. PMID- 22300032 TI - Role of alpha7-nicotinic acetylcholine receptor in normal and cancer stem cells. AB - The alpha7-nicotinic acetylcholine receptor (alpha7-nAChR) is widely known as a neurotransmitter receptor in nervous systems. alpha7-nAChR is also present in a variety of non-neuronal tissues, where it has been implicated in the regulation of essential cellular functions including proliferation, survival, differentiation and communication. We have recently found in breast cancer that alpha7-nAChR is involved in the proliferation of cancer stem cells, which constitute a minor subpopulation responsible for tumor development and metastasis. Since growing evidence suggests that alpha7-nAChR is present not only in mature tissues and organs but also in undifferentiated stem cells and progenitor cells, alpha7-nAChR emerges as a key mediator in the regulation of self-renewal and differentiation. We provide here an overview of the recent works on the expression and function of alpha7-nAChR in normal and cancer stem cells, and their relevance to disease-related cellular dysfunction. Understanding the role of alpha7-nAChR in stem cells would be of great interest for its application potential in drug discovery and in regenerative medicine. PMID- 22300033 TI - alpha7 nAChR in airway respiratory epithelial cells. AB - This review examines the role of alpha7 nAChR in different types of airway epithelial cells of the normal human bronchial tree. In each of these cells alpha7 nAChR activation elicits a specific effect. The effect is essentially mitogenic, whereas in the airway basal cells are antiproliferative. It is postulated that alpha7 nAChR may have mitogenic or antiproliferative signals differentially activated in different types of airway cells and under exposure to exogenous stimuli such as nicotine. PMID- 22300034 TI - alpha7 nicotinic acetylcholine receptor subunit in angiogenesis and epithelial to mesenchymal transition. AB - Cigarette smoking is strongly correlated with many diseases like cancer, cardiovascular disease and macular degeneration. Nicotine, the main active and addictive component of tobacco smoke has recently been shown to enhance angiogenesis in many experimental systems and animal models. The pro-angiogenic activity of nicotine is mediated by nicotinic acetylcholine receptors, particularly the alpha 7 subunit, that are expressed on a variety of non-neuronal cells including those in the vasculature such as endothelial cells and smooth muscle cells. The present review focuses on the role of alpha7nAChR in mediating the pro-angiogenic effects of nicotine and describes the molecular mechanisms involved in nicotine-induced angiogenesis as well as epithelial to mesenchymal transition. These observations on nicotine function highlight the therapeutic potential of alpha7nAChR agonists and antagonists for combating angiogenesis related diseases. PMID- 22300035 TI - Regulatory role of the alpha7nAChR in cancer. AB - Exposure to tobacco products is responsible for the majority of all human cancers. Nicotinic acetylcholine receptors (nAChRs) were identified as early as 1989 as important regulators of cancer cells. In analogy to its function in the brain, the homomeric alpha7nAChR has "accelerator function" on the most common human cancers by stimulating the synthesis and release of excitatory neurotransmitters (serotonin in small cell lung cancer, noradrenaline/adrenaline in most other cancers) that drive cell proliferation, migration, angiogenesis, neurogenesis and metastasis while inhibiting apoptosis. These effects are not only caused by alpha7nAChRs expressed in cancer cells but also by alpha7nAChRs in ganglia and nerves of the sympathetic part of the autonomic nervous system that release noradrenaline/adrenaline into the tumor environment. In the nervous system, alpha7nAChR protein undergoes paradoxical upregulation without concomitant desensitization upon chronic exposure to nicotine. The same phenomenon has been reported for alpha7nAChR expressed in cancer cells of the lungs and pancreas where chronic nicotine or nicotine-derived nitrosamines upregulated the receptor protein, resulting in hyperactivity of its effectors. Strategies that target the alpha7nAChR for cancer intervention are highly promising but should aim to reduce signaling downstream of the receptor rather than blocking the receptor because of its numerous vital functions in the mammalian organism. PMID- 22300036 TI - Is alpha7-nAChR a possible target for lung cancer and malignant pleural mesothelioma treatment? AB - This paper discusses the potential therapeutic effect of alpha7-nAChR antagonists for NSCLC (non small cell lung cancer) and MPM (malignant pleural mesothelioma). This therapeutic approach is based on the experimental observations that: (a) functional alpha7-nAChR are expressed in NSCLC and MPM cells, (b) the activation of these receptors by agonists, namely nicotine, induces cell proliferation and inhibits apoptosis, whereas antagonists have a pro-apoptotic effect. Among competitive alpha7-nAChR antagonists, d-tubocurarine and -cobratoxin (alpha-CbT), from the snake venom of Naja, emerged as possible drug candidates. However, some aspects of the samples must be particularly taken into account, such as the particular nature of the sample. Thus, when using natural compounds purified from snake venom, it is important to take into account the factors such as whether the venom sample was derived from different animals, purified by different methods, or contained contaminants of the same molecular weight. Finally, biological activity may be different for different batches, which could also have been stored under different conditions (e.g. temperature, dilution, suspension medium etc.). These factors, affecting the experimental results, are also discussed. PMID- 22300037 TI - alpha7 nicotinic acetylcholine receptors: a therapeutic target in the structure era. AB - The nicotinic acetylcholine receptors (nAChR) are ligand-gated ion channels involved in cognitive processes and are associated with brain disorders which makes them interesting drug targets. This article presents a general overview of the receptor to introduce the alpha7 nAChR as a drug target. The advances in understanding of the structure/function properties of the nAChR produced during the last decade are detailed as they are crucial for rational drug design. The allosteric properties of the nAChR will also be described because they also have important consequences for drug design. PMID- 22300038 TI - The alpha7 nicotinic acetylcholine receptor complex: one, two or multiple drug targets? AB - The alpha7 nicotinic acetylcholine receptor (nAChR) is a promising drug target for a number of diseases ranging from schizophrenia and Alzheimer's disease to chronic pain and inflammatory diseases. Focusing on the central nervous system, we describe how endogenous and experimental compounds and proteins regulate expression and function of the alpha7 nAChR. Drug development efforts have hitherto focused on direct manipulation of the alpha7 nAChR, but it is still not clear, whether agonism/antagonism or allosteric modulation is preferable as a potential drug therapy. In addition, the action of such compounds in vivo is highly dependent on alpha7 nAChR-interacting proteins, such as RIC-3 and lynx1, which modulate expression and function of the receptor. These regulatory proteins are often not expressed in in vitro models used to study alpha7 nAChR function, and it is not known to what extent they are involved in diseases such as schizophrenia and Alzheimer's disease. Furthermore, alpha7 nAChR agonists and allosteric modulators differentially alter expression and functionality of the alpha7 nAChR with repeated administration, which suggests that there may be fundamentally different outcomes of long-term administration with these different types of compounds. Finally, we describe the special case of Abeta1-42 binding to the alpha7 nAChR, which may pose a unique challenge to drug development of alpha7 nAChR-specific ligands for Alzheimer's disease. Hopefully, a greater knowledge of the many factors influencing alpha7 nAChR function as well as an increasing pipeline of specific drug candidates, enabling a more subtle manipulation of alpha7 nAChR function, may facilitate alpha7 nAChR drug development efforts. PMID- 22300039 TI - The Yin and Yang of non-neuronal alpha7-nicotinic receptors in inflammation and autoimmunity. AB - The alkaloid nicotine, a major addictive component of tobacco, exerts anti inflammatory and immunemodulating activities on multiple cell types, such as T cells, B cells, dendritic cells, mononuclear phagocytes and polymorphonuclear leukocytes, in lung, spleen, liver, kidney and gastrointestinal tract. In addition, nicotine may blunt pro-inflammatory cytokine release, with prominent effects on T helper type 1 (Th1) and Th17 cytokines. The nonneuronal alpha7 nicotinic cholinergic receptors are a primary target for nicotine through the JAK2 and STAT3/NF-kappaB pathways, ultimately mediating the inhibition of pro inflammatory gene transcription. The present paper reviews the growing evidence in favor of detrimental as well as beneficial effects of nicotine and other alpha7-nicotininc receptor agonists in pre-clinical models of organ-specific and systemic inflammatory and autoimmune diseases. These data may portend favorable implications for the targeted treatment of chronic and debilitating human disorders, such as diabetes, arthritis, asthma and inflammatory bowel disease, with alpha7-selective ligands. PMID- 22300040 TI - A new "era" for the alpha7-nAChR. AB - The alpha7-nAChR plays critical roles in numerous organs and cells by regulating highly organ and cell typespecific functions. In this special issue different Authors have contributed to clarify the different roles played by the alpha7- nAChR. Post-translational processes such as receptor "underactivation" or "overactivation" are associated in the central nervous system with brain disorders including neurodegeneration, while also contributing to the regulation of nonneuronal cells and cancers derived from them. Current advances in the knowledge of alpha7-nAChR biology encourage the exploitation of this receptor as a therapeutic target for a variety of diseases, including Alzheimer's, disease, Parkinson's disease, cognitive decline, pain and cancer. PMID- 22300041 TI - Concluding notes of special issue "alpha-7 nicotinic receptor (alpha7-nAChR): one target different diseases". PMID- 22300042 TI - Characterization of asthma exacerbations in primary care using cluster analysis. AB - RATIONALE: Patients with a history of asthma exacerbations are at a higher risk for future episodes of severe asthma exacerbations. Characterization of asthma phenotypes could help improve asthma management, including reducing exacerbations. AIM: The aim of this study is to identify distinctive patient characteristics associated with a history of asthma exacerbations using cluster analysis. METHODS: We used data assessing asthma control from two cross-sectional surveys of adult and pediatric patients in the primary care setting. A supervised cluster analysis with recursive partitioning approach was applied to identify characteristics that maximized the differences across subgroups. RESULTS: The sample comprised 2205 adults and 2435 children and adolescents with asthma. Key predictors were identified in seven adult clusters including visiting an asthma specialist, number of hours worked, and excessive use of rescue medication. The rate ratio (RR) for having an exacerbation was significantly higher (2.88; 95% confidence interval (CI), 2.46-3.36) in Cluster 7, with more female patients reporting severe disease, high body mass index, sinus infections, gastroesophageal reflux disease, skin allergies, and lower asthma control score. Features identified in the six pediatric clusters included visiting an asthma specialist, missed school days, race/ethnicity, and age. The RR for having an exacerbation was higher in Cluster 6 (2.36; 95% CI, 2.11-2.64), with patients reporting more severe disease, sinus and skin allergies, and lower asthma control score. CONCLUSIONS: Identification of specific risk factors can be enhanced by using supervised cluster analysis. This approach allows grouping of patients with unique characteristics to help identify patients at higher risk of exacerbations. PMID- 22300043 TI - Breast molecular imaging: a retrospective review of one institutions experience with this modality and analysis of its potential role in breast imaging decision making. AB - Breast Molecular Imaging (or Breast-Specific Gamma Imaging) has been previously shown to be both sensitive and specific for the detection of breast cancer. The purpose of our study was to retrospectively review all cases of Breast Molecular Imaging (BMI) performed at our institution to determine BMI's potential role in Breast Imaging decision making. A total of 416 cases of BMI from January 2007 to November 2009 were analyzed and the following data were collected: indication for examination, BIRADS assignment after BMI, biopsy outcomes, sensitivity and specificity of the modality and patient follow-up. Fifty-six percent of cases were ordered for an indeterminate asymmetry or focal asymmetry, 14% for evaluation of calcifications, and less than 10% each for the remainder of the indications including palpable lumps with negative imaging, evaluation of extent of disease in patients with known breast cancer and screening of high risk patients who could not undergo MRI. BMI was also shown to be helpful in evaluation of lesions that were difficult to biopsy or for patients that desired further testing rather than biopsy or short term follow-up of abnormalities. Seventy percent of BMI cases performed completed the diagnostic evaluation with BIRADS 1 or BIRADS 2 designations. Only 14% of cases ultimately resulted in biopsy. Contra-lateral findings were discovered in 10% of patients, more than half of which were occult malignancies or high-risk lesions. Of the lesions for which biopsy was recommended, 43% were malignant and 15% were high-risk lesions. Sensitivity of the test at our institution was 93% and specificity 78.9%. Our results show that BMI is both a sensitive and specific test which is useful as an adjunct to standard breast imaging modalities for problem solving in indeterminate cases. PMID- 22300044 TI - Estimation of pulmonary vascular resistance: correlation between echocardiography and catheterization data in patients with congenital heart disease. AB - BACKGROUND: The ratio of peak tricuspid regurgitation velocity (TRV) and right ventricular outflow time-velocity integral (TVI RVOT) has been described as a good correlate of pulmonary vascular resistance (PVR). However, this method has not been well studied in congenital heart disease. METHOD: Twenty patients with post-tricuspid shunt lesions who were planned to undergo cardiac catheterization were enrolled for the study. The ratio of TRV/TVI(RVOT) was measured via transthoracic echocardiography and correlated with invasively derived PVR (PVR(CATH)). PVR(CATH) was measured by cardiac catheterization. Fick's principle was used to calculate the pulmonary blood flow and oxygen consumption was assumed. Linear regression analysis was done to find the correlation between TRV/TVI(RVOT) and PVR(CATH). RESULTS: There was a significant correlation between the two variables, r = 0.635(P = 0.003). Subgroup analysis revealed that this correlation was better at lower values of PVR(CATH) (r = 0.817 for PVR < 6 Wood units (WU)) than higher values (r = 0.659 for PVR > 6 WU). TRV/TVI(RVOT) ratio of greater than 0.145 predicted with 80% sensitivity and specificity a PVR > 6 WU. CONCLUSIONS: There is modest correlation between TRV/TVI(RVOT) ratio and invasively derived PVR in congenital shunt lesions, especially in PVR < 6 WU. TRV/TVI(RVOT) ratio could be useful in identifying patients with congenital shunts whose PVR is likely to be <6 WU, and hence, do not need cardiac catheterization. PMID- 22300045 TI - Evolution of class A G-protein-coupled receptors: implications for molecular modeling. AB - Class A or rhodopsin-like G-protein-coupled receptors (GPCRs) constitute the largest transmembrane receptor family of the human genome. Because of their biological and pharmaceutical importance, the evolutionary history of these receptors has been widely studied. Most studies agree on the classification of the 700 members of this family into a dozen of sub-families. However, the relationship between these sub-families remains controversial and the molecular processes that drove the evolution and diversification of such a large family have still to be determined. We review here the evolutionary analyses carried out on class A GPCRs either by phylogenetic methods or by multidimensional scaling (MDS). We detail the key molecular events driving the evolution of this receptor family. We analyze these events in view of the recently resolved crystal structures of GPCRs and we discuss the usefulness of evolutionary information to help molecular modeling. PMID- 22300047 TI - Recent progress in understanding of structure, ligand interactions and the mechanism of activation of the beta2-adrenergic receptor. AB - The understanding of beta2-adrenergic receptor (beta2AR) interactions with ligands as well as the mechanism of receptor activation changed radically from 2007, when the first crystallographic structure of the receptor was reported. Since then numerous crystallographic studies described interactions with all main classes of beta2AR ligands and with G proteins, which provided a great insight into the molecular structure of the receptor. However, molecular mechanisms of receptor activations remain to be determined. Functional research supported the concept of ligand-directed signaling at beta-adrenoceptors. Agonist can activate alternative signaling pathways with different capacities and trigger cellular effects. It indicates that agonists nominally belonging to the same class may bind to and/or stabilize different active conformations of the receptor which are selectively recognized by signaling proteins in the allosteric manner. PMID- 22300046 TI - Action of molecular switches in GPCRs--theoretical and experimental studies. AB - G protein coupled receptors (GPCRs), also called 7TM receptors, form a huge superfamily of membrane proteins that, upon activation by extracellular agonists, pass the signal to the cell interior. Ligands can bind either to extracellular N terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (Rhodopsin-like family). They are all activated by agonists although a spontaneous auto-activation of an empty receptor can also be observed. Biochemical and crystallographic methods together with molecular dynamics simulations and other theoretical techniques provided models of the receptor activation based on the action of so-called "molecular switches" buried in the receptor structure. They are changed by agonists but also by inverse agonists evoking an ensemble of activation states leading toward different activation pathways. Switches discovered so far include the ionic lock switch, the 3-7 lock switch, the tyrosine toggle switch linked with the nPxxy motif in TM7, and the transmission switch. The latter one was proposed instead of the tryptophan rotamer toggle switch because no change of the rotamer was observed in structures of activated receptors. The global toggle switch suggested earlier consisting of a vertical rigid motion of TM6, seems also to be implausible based on the recent crystal structures of GPCRs with agonists. Theoretical and experimental methods (crystallography, NMR, specific spectroscopic methods like FRET/BRET but also single-molecule-force-spectroscopy) are currently used to study the effect of ligands on the receptor structure, location of stable structural segments/domains of GPCRs, and to answer the still open question on how ligands are binding: either via ensemble of conformational receptor states or rather via induced fit mechanisms. On the other hand the structural investigations of homoand heterodimers and higher oligomers revealed the mechanism of allosteric signal transmission and receptor activation that could lead to design highly effective and selective allosteric or ago-allosteric drugs. PMID- 22300049 TI - Crosstalk within GPCR heteromers in schizophrenia and Parkinson's disease: physical or just functional? AB - Crosstalk between G protein-coupled receptors (GPCRs) is one of the key mechanisms used by the cell for integrating multiple signaling pathways. Functional crosstalk at the level of signaling pathways was initially thought to regulate receptor function. Importantly, the existence of GPCR heteromers demonstrates that direct physical interactions between GPCRs could also be behind the crosstalk phenomenon. Neurological disorders such as Parkinson's disease (PD) and schizophrenia have been linked to a dysfunctional communication between certain GPCRs. In this review, we discuss functional and physical crosstalk of the main GPCR families involved in the aforementioned disorders. In addition, we analyze the available structural information on physical crosstalk and highlight some strategies in drug discovery based on these crosstalk mechanisms. PMID- 22300048 TI - Ensemble of G protein-coupled receptor active states. AB - G protein-coupled receptors (GPCRs) play critical roles in cellular signal transduction and are important targets for therapeutics. Although these receptors have been intensely studied for quite some time, our understanding about their mechanism of action is still incomplete. GPCR activity has traditionally been viewed within the context of two-state models where the receptor is in equilibrium between a single inactive state and a single active state. This framework is too simple and restrictive to accommodate more recent observations made on these receptors, which instead point to a situation where the receptor can adopt several different active conformational substates with distinct functional effects. Structural and functional evidence for this emerging view is presented in this review. Implications of this emerging view in rationalizing diseased states and in drug discovery are also discussed. PMID- 22300050 TI - A closer look into G protein coupled receptor activation: X-ray crystallography and long-scale molecular dynamics simulations. AB - G protein coupled receptors (GPCRs) are a large eukaryotic protein family of transmembrane receptors that react to a signal coming from the extracellular environment to generate an intracellular response through the activation of a signal transduction pathway mediated by a heterotrimeric G protein. Their diversity, dictated by the multiplicity of stimuli to which they respond and by the variety of intracellular signalling pathways they activate, make them one of the most prominent families of validated pharmacological targets in biomedicine. In recent years, major breakthroughs in structure determination of GPCRs have given new stimuli to the exploration of the biology of these proteins, providing a structural basis to understand the molecular origin of GPCR mechanisms of action. Based on the information coming from these structural studies, a number of recent in silico investigations used molecular dynamics (MD) simulations to contribute to our knowledge of GPCRs. In this review, we will focus on investigations that, taking advantage of the tremendous progress in both hardware and software, made testable hypotheses that have been validated by subsequent structural studies. These stateof- the-art molecular simulations highlight the potential of microsecond MD simulations as a valuable tool in GPCR structural biology and biophysics. PMID- 22300051 TI - Molecular pathways involved in the early and late damage induced by testis ischemia: evidence for a rational pharmacological modulation. AB - Testicular torsion or torsion of the spermatic cord is a surgical emergency in which misdiagnosis and inappropriate treatment can lead to male infertility. Events occurring during testicular torsion and detorsion are representative of an ischemia-reperfusion injury observed in other organs. The two most important factors determining testicular damage are the degree of twisting and the early onset of a surgical treatment to counter-rotate both testis and spermatic cord for inducing reperfusion. The damage from reperfusion is more severe than that induced by ischemia and several mechanisms are implicated in the development of testicular damage following torsion and detorsion. However, these mechanisms have not yet been fully clarified and, as a consequence, there is still a strong need to identify specific pharmacological treatment to limit the damage triggered by the reperfusion procedures. Ischemia and reperfusion of testis result in elevated production of reactive oxygen species (ROS), activate mitogen activated protein kinases (MAPKs) and PPARbeta/delta receptor, induce transcription factors and growth factors including NF-kappaB and VEGF, trigger apoptotic machinery and induce several inflammatory cytokines, including TNF-alpha and IL-1beta . This pathological cascade is responsible for the testicular atrophy, decreased blood flow and impaired spermatogenesis. Several pharmacological approaches have been characterized as promising therapeutic agents for the management of testicular torsion and may be useful to ameliorate the sequel of this disease. PMID- 22300053 TI - Implications of incomplete sampling on a statistical form of the ambient air quality standard for particulate matter. PMID- 22300052 TI - Evaluation of PCR for the diagnosis of dermatophytes in nail specimens from patients with suspected onychomycosis. AB - BACKGROUND: Conventional methods for detecting fungi in nail specimens are either nonspecific (microscopy) or insensitive (culture). Recently, PCR has been used to improve sensitivity in detecting the causative fungi in nail specimens from patients with suspected onychomycosis. AIM: To compare the detection rates of PCR with those of microscopy (with potassium hydroxide; KOH) and culture for dermatophytes in nail specimens from patients with suspected onychomycosis. METHODS: In total, 120 patients with clinically suspected onychomycosis were recruited, and using a topoisomerase II-based PCR, we compared the detection rate of dermatophytes for the three methods. RESULTS: KOH microscopy, culture and PCR respectively yielded positive rates of 35 (29.2%), 12 (10%) and 48 (40%), and negative rates of 85 (70.8%), 108 (90%) and 72 (60%). Two culture-positive specimens were not detected by PCR, but PCR picked up 38 specimens missed by culture. Of the 35 specimens that were microscopy-positive, 12 grew dermatophytes and 23 nondermatophytes. CONCLUSIONS: This study demonstrates that PCR has a higher positive and lower negative rate for detection of dermatophytes compared with KOH microscopy or culture. We suggest that PCR should be used as a complementary method for confirmation of clinically suspected dermatophytic onychomycosis. PMID- 22300054 TI - Urban runoff as a source of polycyclic aromatic hydrocarbons to coastal waters. PMID- 22300055 TI - Solubility of organic mixtures in water. PMID- 22300057 TI - Trace nitrogen-containing species in the offgas from two oil shale retorting processes. PMID- 22300056 TI - Trace sulfur-containing species in the offgas from two oil shale retorting processes. PMID- 22300058 TI - Fluorescence spectroscopic study of reactions between gaseous ozone and surface adsorbed polycyclic aromatic hydrocarbons. PMID- 22300059 TI - Biochemical and photochemical processes in the degradation of chlorinated biphenyls. PMID- 22300061 TI - Reduction and dissolution of manganese(III) and manganese(IV) oxides by organics: 2. Survey of the reactivity of organics. PMID- 22300060 TI - High-velocity inertial impactors. PMID- 22300062 TI - Evidence for the long-distance atmospheric transport of polychlorinated terphenyl. PMID- 22300063 TI - Comparison of the carcinogenic risks from fish versus groundwater contamination by organic compounds. PMID- 22300065 TI - Comments on: "Acid precipitation in historical perspective" and "Effects of acid precipitation" (rebuttal). PMID- 22300064 TI - Comment on "Acid precipitation in historical perspective" and "Effects of acid precipitation". PMID- 22300067 TI - Suppressive effects of liquid crystal compounds on the growth of U937 human leukemic monocyte lymphoma cells. AB - BACKGROUND: The aim of this study was to evaluate the biological and pharmaceutical activities of 14 amphiphilic liquid-crystalline compounds (LCs), i.e, phenylpyrimidine derivatives possessing D-glucamine and cyanobiphenyl derivatives with a terminal hydroxyl unit. RESULTS: The cytotoxic properties of the LCs on the cell growth, cell cycle distribution, and cell signaling pathway of U937 human leukemic monocyte lymphoma cells were assessed by flow cytometry and western blot analysis. Some LCs showed cytostatic effects, suppressing cell growth via S-phase arrest and without apoptosis in U937 cells. To investigate the mechanisms of the LC-induced S-phase arrest, proteins relevant to cell cycle regulation were investigated by western blot analysis. The rate of LC-induced S phase arrest was congruent with the decreased expression of MCM2, cyclin A, cyclin B, CDK2, phospho-CDK1 and Cdc25C. Observed changes in cell cycle distribution by LC treated might be caused by insufficient preparation for G2/M transition. Considering the structure of the LCs, the rod-like molecules displaying cytotoxicity against U937 cells possessed flexible spacers with no bulky polar group attached via the flexible spacer. CONCLUSIONS: Our results revealed that some LCs showed cytotoxic properties against non-solid type tumor human leukemic cells via LC-induced S-phase arrest and decreasing expression of several cell cycle related proteins. PMID- 22300068 TI - Adherence with migraine prophylaxis in clinical practice. AB - OBJECTIVE: To characterize adherence with antidepressants, antiepileptic drugs, and beta blockers as prophylaxis against migraine in typical clinical practice. METHODS: Using a large US health insurance claims database (calendar years 2003 to 2005), we identified all patients with migraine who began prophylaxis with selected antidepressants, antiepileptic drugs, or beta blockers ("study agents"). Patients not continuously enrolled for 6 months prior to start of prophylaxis ("pretreatment") and for 6 months subsequently ("follow-up") were excluded. Treatment cohorts were constituted based on the type of prophylaxis received. Adherence with migraine prophylaxis was examined by type of agent received using medication possession ratios (MPRs), defined as total days with medication divided by total follow-up days. MPR < 0.80 was considered indicative of nonadherence. RESULTS: A total of 4,634 patients met all entry criteria and received antidepressants (n = 1,803), antiepileptics (n = 1,896), or beta blockers (n = 935) on their index date. Over the next 6 months, the mean (SD) number of prescriptions for study agents was 2.7 (1.9) for antidepressants, 2.9 (2.0) for antiepileptics, and 2.8 (2.0) for beta blockers, totaling 91.0 (71.4), 98.7 (75.6), and 96.7 (73.0) therapy-days, respectively. Mean MPR at 6 months was 0.48 for antidepressants, 0.51 for antiepileptics, and 0.51 for beta blockers. By the end of the follow-up, 73.4%, 70.2%, and 67.6% of patients who initiated migraine prophylaxis with antidepressants, antiepileptics, and beta blockers, respectively, were designated nonadherent (ie, MPR < 0.80). CONCLUSION: Our findings suggest that many patients who begin migraine prophylaxis with antidepressants, antiepileptics, or beta blockers are no longer taking these medications at 6 months. PMID- 22300069 TI - A preliminary study to find a possible association between occlusal wear and maximum bite force in humans. AB - OBJECTIVE: The objective of the study was to investigate whether moderate-to severe attrition is associated with maximum bite force in the first molar region. METHODOLOGY: Maximum bite force in the first molar region was measured for a total of 60 subjects having moderate-to-severe attrition of occlusal surface (experimental group) using a specially-designed piezoelectric sensor based bite force measuring device. An equal number of age, gender, height and weight matched controls (control group) were also subjected to bite force measurement for comparison. RESULTS: The maximum bite force was found to be significantly lower (p < 0.05) in the experimental group [480.32 (153.40)] as compared to the controls [640.63 (148.90)]. While analyzing the possible etiology for occlusal wear mainly two reasons were elicited, i.e. history of parafunctional habits like use of known abrasive tooth powder (sub-group A) and Bruxism (sub-group B). However, there were many subjects in which no known definite etiological factors be attributed to occlusal wear (sub-group C). On analysing further with respect to the possibly correlated etiological factors with maximum bite force, no significant difference was found within the experimental sub-group. However, all three experimental sub-groups had significantly lower maximum bite force as compared to age, gender and BMI matched controls. CONCLUSION: A significantly lower maximum bite force was found to be associated with moderate-to-severe attrition as compared to subjects without attrition. However, no specific relation could be found between bite force and possible etiological factors like history of parafunctional habits, history of use of known abrasive tooth powder, etc. PMID- 22300070 TI - Novel physiological and pharmacological avenues in the mechanism of gastrointestinal integrity, protection and ulcer healing. PMID- 22300071 TI - The mechanisms of gastric mucosal injury: focus on microvascular endothelium as a key target. AB - This paper reviews and updates current views on gastric mucosal injury with a focus on the microvascular endothelium as the key target and the role of the anti apoptosis protein survivin. Under normal conditions, mucosal integrity is maintained by well structured and mutually amplifying defense mechanisms, which include pre-epithelial "barrier"--the first line of defense; and, an epithelial "barrier". Other important defense mechanisms of gastric mucosa include: continuous epithelial cell renewal, blood flow through mucosal microvessels (providing oxygen and nutrients), an endothelial microvascular "barrier," sensory innervation, and generation of PGs, nitric oxide and hydrogen sulfide. The microvascular endothelium lining gastric mucosal blood microvessels severs not only as a barrier but is a biologically active tissue involved in many synthetic and metabolic functions. It allows transport of oxygen and nutrients, and produces prostaglandins and leukotriens, procoagulant factors, nitric oxide, endothelin, ghrelin, HSP, growth factors such VEGF, bFGF, angiopoietin 2 and others, specific types of collagen, plasminogen activator, and can also actively contract. Accumulating evidence indicates that the gastric microvascular endothelium is a critical target for injury by ethanol, NSAIDs, free radicals, ischemia-reperfusion and other damaging factors. The injury--microvessel rupture, plasma and erythrocyte extravasation, platelet aggregation and fibrin deposition caused by these damaging factors--occurs early (1-5 min), precedes glandular epithelial cell injury and results in cessation of blood flow, ischemia, hypoxia and impaired oxygen and nutrient transport. As a consequence, mucosal necrosis develops. One of the main reasons for the increased susceptibility of gastric microvascular endothelial (vs. epithelial) cells to injury is reduced expression levels of survivin, an anti-apoptosis protein, which is a regulator of both proliferation and cell survival. PMID- 22300072 TI - Molecular mechanisms of epithelial regeneration and neovascularization during healing of gastric and esophageal ulcers. AB - In this paper we reviewed and updated current views on the cellular and molecular mechanisms of gastric and esophageal ulcer healing. Gastric ulcer healing encompasses inflammation, cell proliferation, epithelial regeneration, gland reconstruction, formation of granulation tissue, neovascularization (new blood vessel formation), interactions between various cells and the matrix and tissue remodeling, resulting in scar formation. All these events are controlled by the cytokines and growth factors, GI hormones including gastrin, CCK, and orexigenic peptides such as ghrelin, orexin-A and obestatin as well as Cox2 generated prostaglandins. These growth factors and hormones trigger cell proliferation, migration, and survival utilizing Ras, MAPK, PI-3K/AKT, PLC-gamma and Rho/Rac/actin signaling pathways. Hypoxia triggers activation of some of these genes (e.g., VEGF) via hypoxia inducible factor (HIF). Growth factors: EGF, HGF, IGF-1, their receptors and Cox2 are important for epithelial cell proliferation, migration, re-epithelialization and regeneration of gastric glands during gastric ulcer healing. Serum response factor (SRF) is also essential for re epithelialization and muscle restoration. VEGF, bFGF, angiopoietins, nitric oxide, endothelin, prostaglandins and metalloproteinases are important for angiogenesis, vascular remodeling and mucosal regeneration within gastric ulcer scar. SRF is critical limiting factor for VEGF-induced angiogenesis. Esophageal ulcer healing follows similar pattern to gastric ulcer, but KGF and its receptor are the key players in regeneration of the epithelium. In addition to local mucosal cells from viable mucosa bordering necrosis, circulating bone marrow derived stem and progenitor cells are potentially important for ulcer healing, contributing to the regeneration of epithelial and connective tissue components and neovascularization. PMID- 22300073 TI - Recent advances in gut nutrient chemosensing. AB - The field of gut nutrient chemosensing is evolving rapidly. Recent advances have uncovered the mechanism by which specific nutrient components evoke multiple metabolic responses. Deorphanization of G protein-coupled receptors (GPCRs) in the gut has helped identify previously unliganded receptors and their cognate ligands. In this review, we discuss nutrient receptors, their ligand preferences, and the evoked neurohormonal responses. Family A GPCRs includes receptor GPR93, which senses protein and proteolytic degradation products, and free fatty acid sensing receptors. Short-chain free fatty acids are ligands for FFA2, previously GPR43, and FFA3, previously GPR41. FFA1, previously GPR40, is activated by long chain fatty acids with GPR120 activated by medium- and long-chain fatty acids. The GPR119 agonist ethanolamide oleoylethanolamide (OEA) and bile acid GPR131 agonists have also been identified. Family C receptors ligand preferences include L-amino acids, carbohydrate, and tastants. The metabotropic glutamate receptor (mGluR), calcium-sensing receptor (CaR), and GPCR family C, group 6, subtype A receptor (GPRC6A) mediate L-amino acid-sensing. Taste receptors have a proposed role in intestinal chemosensing; sweet, bitter, and umami evoke responses in the gut via GPCRs. The mechanism of carbohydrate-sensing remains controversial: the heterodimeric taste receptor T1R2/T1R3 and sodium glucose cotransporter 1 (SGLT 1) expressed in L cells are the two leading candidates. Identification of specific nutrient receptors and their respective ligands can provide novel therapeutic targets for the treatment of diabetes, acid reflux, foregut mucosal injury, and obesity. PMID- 22300075 TI - Gas mediators involved in modulating duodenal HCO3(-) secretion. AB - The secretion of HCO3(-) in the duodenum is increased by mucosal acidification, and this process is modulated by gas mediators such as nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO), in addition to prostaglandins (PGs). The secretion is increased by NOR3 (NO donor), NaHS (H2S donor), and CORM 2 (CO donor). The HCO3(-) responses to NOR3 and CORM-2 are attenuated by indomethacin, while that to NaHS is mitigated by indomethacin and L-NAME as well as sensory deafferentation. NOR3 and CORM-2 increase mucosal PGE2 production, while H2S increases mucosal PGE2 content and luminal NO release. The HCO3(-) response to mucosal acidification is attenuated by indomethacin, propargylglycine, and SnPP, each inhibiting PG, H2S and CO production, respectively. The acid-induced duodenal damage is worsened when either PG, H2S or CO is lacking. These findings suggest that 1) NO, H2S, and CO, generated endogenously or exogenously, stimulate HCO3(-) secretion in the duodenum; 2) the stimulatory action of NO and CO is mediated, at least partly, by endogenous PGs, while that of H2S is mediated by PGs and NO as well as sensory neurons; 3) these gas mediators are involved in the local regulation of acid-induced HCO3(-) secretion, in addition to endogenous PGs; 4) the acid-induced duodenal damage is worsened by agents inhibiting the endogenous production of NO, H2S or CO. It is assumed that these gas mediators play a role in maintaining the integrity of the duodenal mucosa by modulating the secretion of HCO3(-). PMID- 22300076 TI - Novel concept in the mechanism of injury and protection of gastric mucosa: role of renin-angiotensin system and active metabolites of angiotensin. AB - The term cytoprotection pioneered by Robert and colleagues has been introduced to describe the remarkable ability of endogenous and exogenous prostaglandins (PGs) to prevent acute gastric hemorrhagic lesions induced by noxious stimuli such as ethanol, bile acids, hiperosmolar solutions and nonsteroidal anti-inflammatory agents such as aspirin. Since that time many factors were implicated to possess gastroprotective properties such as growth factors including epidermal growth factor (EGF) and transforming factor alpha (TGFalpha), vasodilatory mediators such as nitric oxide (NO) and calcitonin gene related peptide (CGRP) as well as appetite gut hormones including gastrin and cholecystokinin (CCK), leptin and recently ghrelin. This protective action of gut peptides has been attributed to the release of PG but question remains whether another peptide angiotensin, the classic component of the systemic and local renin-angiotensin system (RAS) could be involved in the mechanism of gastric integrity and gastroprotection. After renin stimulation, the circulating angiotensin I is converted to angiotensin II (ANG II) by the activity of the Angiotensin Converting Enzyme (ACE). The ANG II acting via its binding to two major receptor subtypes the ANG type 1 (AT1) and type 2 (AT2) has been shown be activated during stress and to contribute to the pathogenesis of cold stress- and ischemia-reperfusion-induced gastric lesions. All bioactive angiotensin peptides can be generated not only in systemic circulation, but also locally in several tissues and organs. Recently the new functional components of RAS, such as Ang-(1-7), Ang IV, Ang-(1-12) and novel pathways ACE2 have been described suggesting the gastroprotective role for the novel ANG II metabolite, Ang-(1-7). The fact that Ang-(1-7) is produced in excessive amounts in the gastric mucosa of rodents and that pretreatment by Ang (1-7) exhibits a potent gastroprotective activity against the gastric lesions induced by cold-restraint stress suggests that this and possibly other vasoactive metabolites of ANG II pathway could be involved in the mechanism of gastric integrity and gastroprotection. This review summarizes the novel gastroprotective factors and mechanisms associated with metabolic fate of systemic and local RAS activation with major focus to recent advancement in the angiotensin pathways in the gut integrity. PMID- 22300077 TI - Effects of cigarette smoke and its active components on ulcer formation and healing in the gastrointestinal mucosa. AB - Ulceration in the gastrointestinal (GI) mucosa is a common disorder in humans. It has been shown that cigarette smoking is closely related to the increase of peptic ulcer and also plays an inhibitory role on ulcer healing. However, the underlying mechanisms by which cigarette smoke exerts these adverse effects remain largely unknown. It is perhaps partly due to the complexity of chemical compositions in the smoke and furthermore their pathological actions are largely undefined. In this review, we have highlighted the potential adverse effects of the toxic chemical components in cigarette smoke and summarized their possible mechanisms of actions on ulcer formation and healing in the GI tract. We also discuss in detail how cigarette smoke disturbs cell proliferation, influences mucus synthesis and secretion, delays blood vessel formation, and interferes the innate immune responses during ulceration and repair in the GI mucosa. PMID- 22300074 TI - Brainstem neuropeptides and vagal protection of the gastric mucosal against injury: role of prostaglandins, nitric oxide and calcitonin-gene related peptide in capsaicin afferents. AB - Earlier experimental studies indicated that the integrity of vagal pathway was required to confer gastric protection against damaging agents. Several peptides located in the brainstem initially identified to influence vagal outflow to the stomach, as assessed by electrophysiological approach or by vagal dependent alterations of gastric secretory and motor function, were investigated for their influence in the vagal regulation of the resistance of the gastric mucosa to injury. Thyrotropin releasing hormone (TRH), or its stable TRH analog, RX-77368, injected at low doses into the cisterna magna or the dorsal motor nucleus (DMN) was the first peptide reported to protect the gastric mucosa against ethanol injury through stimulation of vagal cholinergic pathways, inducing the release of gastric prostaglandins/nitric oxide (NO) and the recruitment of efferent function of capsaicin sensitive afferent fibers containing calcitonin-gene related peptide (CGRP). Activation of endogenous TRH-TRH1 receptor signaling located in the brainstem plays a role in adaptive gastric protection against damaging agents. Since then, an expanding number of peptides, namely peptide YY, CGRP, adrenomedullin, amylin, glugacon-like peptide, opioid peptides acting on u, delta1 or delta2 receptors, nocicpetin, nocistatin, ghrelin, leptin and TLQP-21, a peptide derived from VGF prohormone, have been reported to act in the brainstem to afford gastric protection against ethanol injury largely through similar peripheral effectors mechanisms than TRH. Therefore gastric prostaglandins and CGRP/NO pathways represent a common final mechanism through which brain peptides confer vagally mediated gastroprotection against injury. A better understanding of brain circuitries through which these peptides are released will provide new strategies to recruit integrated and multifaceted gastroprotective mechanisms. PMID- 22300078 TI - Therapeutic potential of carbon monoxide (CO) for intestinal inflammation. AB - The pathogenesis of inflammatory bowel disease (IBD) is complicated and even several therapeutic strategies have been developed, they are not adequate for achieving mucosal remission in all IBD patients. Several reports have described the role of carbon monoxide (CO) in protection against chronic intestinal inflammation. CO has recently emerged as a potent immunomodulatory entity, anti inflammatory agent, and homeostasis of physiological condition. CO reduces lipopolysaccharide-induced proinflammatory cytokines in macrophages via the effect of MAPK pathways. Interleukin-6, one of the important cytokines in the pathogenesis of IBD is also regulated by CO. Epithelial cell restitution is reported to be important factor to control IBD and CO has been reported to enhance colonic epithelial restitution through FGF15/19 expression in colonic myofibroblasts. CO also reduced mucosal damage and inflammation in several experimental animal colitis models such as interleukin-10(-/-) mouse model, TCRalpha(-/-) mouse model, dextran sodium sulfate colitis model, and trinitrobennzen sulfonic acid colitis model. Taken together, CO has anti inflammatory and enhancement of restitution examined in vitro model and in vivo experimental colitis model. These results indicate that CO may have a potential to be one of the therapeutic strategies in IBD patients. PMID- 22300079 TI - Small intestinal injury caused by NSAIDs/aspirin: finding new from old. AB - Small intestinal injury caused by non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin is an epoch making topic in clinical field with the aid of new devices, capsule endoscopy and double balloon enteroscopy to look at small intestine directly. However, the injury has been reported in animals since more than 40 years ago. Proposed mechanisms are impairment of mucosal defense through inhibition of cyclooxygenase (COX) resulting in deficiency of prostaglandins, and mitochondrial disorder. Possible aggressive factors are NSAIDs/aspirin themselves, bile, and enterobacteria. Translocation of enterobacteria through the mucosa impaired integrity may be the first step of the injury. Bacterial lipopolysaccharides stimulate toll-like receptor-4 in macrophages, which increases proinflammatory cytokines through MyD88 signaling pathway. Finally neutrophils are activated and the small intestinal mucosa is injured with the attacks of NSAIDs/aspirin themselves, bile, and proteolytic enzymes and active oxygen species released by neutrophils. Candidates of treatment tools are prostaglandin derivatives, mucoprotective drugs, probiotics, and mitochondrial protective drugs such as metronidazole and cyclosporin A. Further clinical studies are needed to elucidate the effect in humans. PMID- 22300080 TI - Management of NSAID/aspirin-induced small intestinal damage by GI-sparing NSAIDs, anti-ulcer drugs and food constituents. AB - Recent advances in endoscopic techniques such as capsule endoscopy have revealed that aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) often cause mucosal lesions not only in the upper gastrointestinal tract, but also in the small intestine in humans. Gastric and duodenal lesions caused by NSAIDs can be treated with anti-secretory agents such as proton pump inhibitors or histamine H2 receptor antagonists; however, these drugs are ineffective in treating NSAID induced lesions in the small intestine. Furthermore, there are few effective agents for the treatment of small intestinal lesions. Therefore, identification of effective therapies for the treatment of NSAID/aspirin-induced small intestinal lesions remains an urgent priority. In the present review, we focus on novel pharmacological treatments to prevent or reduce NSAID-induced intestinal lesions, i.e., 1) GI-sparing NSAIDs (NO- or H2S-NSAIDs, NSAIDs mixed with phosphatidylcholine); 2) anti-ulcer drugs such as mucosal protective agents (misoprostol, rebamipide, teprenone, etc.) and anti-secretory agents (lansoprazole, etc.); 3) antibiotics (metronidazole) and probiotics (Lactobacillus sp.); and 4) food constituents (lactoferrin and soluble dietary fibers). We surveyed data from clinical trials evaluating these novel treatments. Also reviewed herein were the pros and cons of the novel protective methods from the standpoint of safety, efficacy, convenience, and cost. PMID- 22300081 TI - Critical role of hypoxia sensor--HIF-1alpha in VEGF gene activation. Implications for angiogenesis and tissue injury healing. AB - Vascular injury of esophageal and gastrointestinal mucosa caused by injurious and ulcerogenic factors leads to the cessation of blood flow, ischemia, and hypoxia and tissue necrosis in form of erosions or ulcers. The re-establishment of blood vessels through the process of angiogenesis--formation of new blood vessels--is critical for healing of tissue injury because is essential for delivery of oxygen and nutrients to the healing site. Hypoxia increases expression of hypoxia inducible factor (HIF-1), which serves as hypoxia sensor and activates compensatory and adaptive mechanisms. However, the molecular mechanisms and the role of HIF-1alpha in hypoxia-driven cellular and molecular events of angiogenesis in gastrointestinal injury healing have not been fully explored. The review discusses the novel molecular mechanisms of angiogenesis in gastric and esophageal mucosa with focus on HIF1alpha and VEGF interactions during healing of gastric mucosal injury and esophageal ulcers. HIF-1alpha is upregulated by gastric mucosal injury and esophageal ulcers; this upregulation correlates with VEGF gene activation and initiation of angiogenesis. The non-steroidal anti inflammatory drugs (NSAIDs) interfere with hypoxia-induced HIF-1alpha accumulation, VEGF gene activation and angiogenesis through upregulation of von Hippel- Lindau (VHL) tumor suppressor, which activates degradation of HIF-1alpha protein. HIF-1alpha is a transcription factor that under hypoxic conditions, accumulates in endothelial cells and can bind to VEGF gene promoter and induce VEGF gene expression. In order to activate the VEGF gene, HIF-1alpha must be transported to the nucleus. Recent evidence implicates importins as key mechanism in this process. PMID- 22300082 TI - The ECL cell: relay station for gastric integrity. AB - The term "enterochromaffin cell" was introduced more than 100 years ago. The cells that are morphologically similar to the enterochromaffin cells have been referred to as "enterochromaffin-like cells". One of the enterochromaffin-like cell populations in the oxyntic mucosa of stomach is known to produce and store histamine and chromogranin A, and referred to as ECL cells. The biology and the functional morphology and topology of the ECL cells have been extensively studied, since they were discovered 45 years ago. ECL-cell histamine plays an important role in the regulation of gastric acid secretion, particularly in response to gastrin stimulation. The time-course responses of ECL cells to gastrin include mobilization of histamine, hypertrophy, hyperplasia, dysplasia and formation of ECL-cell carcinoids. The ECL cells are controlled by a complex regulatory system involving endocrine, paracrine and neural pathways. The physiological significance of ECL cells reflects the nature of their products such as histamine, chromogranin A-derived peptides, Reg protein and yet-unknown hormone. PMID- 22300083 TI - Nutraceuticals for protection and healing of gastrointestinal mucosa. AB - Natural medicinal products have been used for millennia for the treatment of several ailments. Although many have been superseded by conventional pharmaceutical approaches, there is currently a resurgence in the interest in natural products by the general public and the use of complementary and alternative medicine is increasing rapidly in developed countries. Also, pharmaceutical industries are more and more interested in examining their potential as sources of novel medicinal compounds which may act as growth factor or show immunomodulatory or anti-microbial activity. The subgroup of natural bioactive compounds that bridge the gap between food products and drugs are termed nutraceuticals or functional foods. In contrast with most standard medicinal compounds, nutraceuticals are generally used to prevent rather than to treat disease. Many of the claims for such products are supported by very limited scientific evidence. However, there has recently been a great interest at evaluating the mechanism by which natural products exert their beneficial effects in the gastrointestinal tract. In particular, a major area of interest is for the use of biologically active chemical components of plants, i.e. phytochemicals, in a number of gastrointestinal disorders. While the major focus of phytochemical research has been on cancer prevention, several products of plant origin are being used and/or under study for a variety of other gastrointestinal problems. In this review we discuss the scientific evidence supporting the potential use of nutraceuticals as agents capable to prevent or accelerate healing of gastrointestinal mucosal damage, with a focus on polyphenol extracts obtained from apple. PMID- 22300084 TI - Protective and therapeutic effects of ghrelin in the gut. AB - Ghrelin, a peptide predominantly produced in the stomach exhibits numerous physiological functions, including stimulation of growth hormone release, food intake and gastric empting, and regulation of energy expenditure. This peptide exhibits also some protective and healing-promoting effects. This review summarizes the recent findings concerning animal and human data showing protective and therapeutic effects of ghrelin in the gut. PMID- 22300085 TI - Focus on ulcerative colitis: stable gastric pentadecapeptide BPC 157. AB - Stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419) may be the new drug stable in human gastric juice, effective both in the upper and lower GI tract, and free of side effects. BPC 157, in addition to an antiulcer effect efficient in therapy of inflammatory bowel disease (IBD) (PL 14736) so far only tested in clinical phase II, has a very safe profile, and exhibited a particular wound healing effect. It also has shown to interact with the NO-system, providing endothelium protection and angiogenic effect, even in severely impaired conditions (i.e., it stimulated expression of early growth response 1 gene responsible for cytokine and growth factor generation and early extracellular matrix (collagen) formation (but also its repressor nerve growth factor 1-A binding protein-2)), important to counteract severe complications of advanced and poorly controlled IBD. Hopefully, the lessons from animal studies, particularly advanced intestinal anastomosis healing, reversed short bowel syndrome and fistula healing indicate BPC 157's high significance in further IBD therapy. Also, this supportive evidence (i.e., no toxic effect, limit test negative, LD1 not achieved, no side effect in trials) may counteract the problems commonly exercised in the use of peptidergic agents, particularly those used on a long term basis. PMID- 22300086 TI - MicroRNAs and chronic inflammation contribution to gastrointestinal integrity. AB - Recent studies have revealed that chronic inflammation represents a major basis for different forms of human malignancies. Chronic inflammations are involved in the pathogenesis of 15-25% of human malignancies. Gastrointestinal (GI) cancer is one of the most common causes of mortality in the European Union. The mechanisms leading to cancer development and its progression are not completely understood. Advances are required both in early detection and therapy of GI cancers. There are many factors connecting inflammation and cancer. Cytokines that are small protein molecules regulating growth, differentiation, development and immune response mechanisms in cells. Overexpression of cyclooxynenase-2 is associated with decreased apoptosis, cell to cell adhesion, increased proliferation and angiogenesis contributes to the increased immunosuppresion and mediates carcinogenetic effects. MicroRNAs are regarded as a novel class of gene expression regulators. They are gene-silencing RNAs which negatively regulate gene expression. After binding to target mRNAs they lead either to mRNA destruction or inhibition of translation. Hence, they can play an important role in carcinogenesis. Currently, almost all of the miRNA-related studies on cancers based on the different expression profile of miRNAs in cancer cells compared to normal cells. In summary, miRNAs, proinflammatory cytokines and other factors, may be involved in cancer development based on chronic inflammation by controlling cell differentiation and apoptosis. Assessing the role of miRNAs will provide the new insights on their contribution to the link between chronic inflammation and subsequent cancer, and new markers for cancer diagnoses and cancer therapy. PMID- 22300087 TI - The role of methylglyoxal-modified proteins in gastric ulcer healing. AB - Methylglyoxal is a reactive dicarbonyl compound produced from cellular glycolytic intermediates that reacts nonenzymatically with proteins to form products such as argpyrimidine at arginine residues. Abnormal accumulation of methylglyoxal and methylglyoxal-derived advanced glycation end products (AGEs) occurs under hyperglycemic conditions and has been implicated in endothelium dysfunction, arterial stiffening, and microvascular complications in diabetes. However, the role of methylglyoxal in the healing process of diabetic gastric ulcers has not been fully investigated. Recently, methylglyoxal modification of peroxiredoxin-VI was found to be associated with delayed healing of diabetic gastric ulcers. Thus, inhibition of methylglyoxal modification might have therapeutic potential for the treatment of such ulcers. In this review, we present what is currently known regarding the role of methylglyoxal in the healing of diabetic gastric ulcers. PMID- 22300088 TI - The inhibition of cell proliferation using silencing of N-cadherin gene by siRNA process in human melanoma cell lines. AB - Malignant melanoma is a disease with high mortality rate caused by rapid metastasis. Cell motility is physically and biochemically restricted by cadherin mediated cell interactions and signalling pathways, and alterations in cadherin expression strongly correlate with E to N-cadherin switch as well as the metastasis and progression of tumours. Contrary to E-cadherin, N-cadherin plays an important role in stimulating processes of cell division, migration, differentiation and death. In this study we investigated the role of N-cadherin in proliferation and AKT, ERK, beta-catenin signalling pathway in human melanoma cells: WM793(VGP), WM115(VGP) from the primary tumor site, as well as Lu1205(lung) and WM266-4(skin) from metastatic sites. N-cadherin, pAKT(S473), beta-catenin, pERK1/2(T202/Y204), cyclin D1, cyclin D3, cyclin-dependent kinases CDK4, CDK6, and p15, p16, p21, p27 inhibitors expression was determined by western blot analysis. The study on proliferation of cells was performed with the use of BrdU incorporation and crystal violet staining assays. Knock-out of N cadherin gene expression by siRNA process reduced the expression of: pAKT(S473), pERK1/2(T202/Y204), betacatenin, cyclin D1, cyclin D3, cyclin-dependent kinases CDK4, CDK6 while increasing expression of cell cycle inhibitors p21 and p27, and significantly decreased cell proliferation (50-70%). The collected data indicate that N-cadherin mediates the effect of cell cycle in G1 phase by AKT, beta catenin, and ERK signalling pathway. These results suggest that increased expression of N-cadherin significantly contributes to the increased invasive potential of melanoma cells. Silencing of N-cadherin arrests cell growth at G1 phase and inhibits the entry into S-phase which is of great importance as to its possible future use in cancer treatment. PMID- 22300089 TI - Measurement and theory of hydrogen bonding contribution to isosteric DNA base pairs. AB - We address the recent debate surrounding the ability of 2,4-difluorotoluene (F), a low-polarity mimic of thymine (T), to form a hydrogen-bonded complex with adenine in DNA. The hydrogen bonding ability of F has been characterized as small to zero in various experimental studies, and moderate to small in computational studies. However, recent X-ray crystallographic studies of difluorotoluene in DNA/RNA have indicated, based on interatomic distances, possible hydrogen bonding interactions between F and natural bases in nucleic acid duplexes and in a DNA polymerase active site. Since F is widely used to measure electrostatic contributions to pairing and replication, it is important to quantify the impact of this isostere on DNA stability. Here, we studied the pairing stability and selectivity of this compound and a closely related variant, dichlorotoluene deoxyriboside (L), in DNA, using both experimental and computational approaches. We measured the thermodynamics of duplex formation in three sequence contexts and with all possible pairing partners by thermal melting studies using the van't Hoff approach, and for selected cases by isothermal titration calorimetry (ITC). Experimental results showed that internal F-A pairing in DNA is destabilizing by 3.8 kcal/mol (van't Hoff, 37 degrees C) as compared with T-A pairing. At the end of a duplex, base-base interactions are considerably smaller; however, the net F A interaction remains repulsive while T-A pairing is attractive. As for selectivity, F is found to be slightly selective for adenine over C, G, T by 0.5 kcal mol, as compared with thymine's selectivity of 2.4 kcal/mol. Interestingly, dichlorotoluene in DNA is slightly less destabilizing and slightly more selective than F, despite the lack of strongly electronegative fluorine atoms. Experimental data were complemented by computational results, evaluated at the M06-2X/6 31+G(d) and MP2/cc-pVTZ levels of theory. These computations suggest that the pairing energy of F to A is ~28% of that of T-A, and most of this interaction does not arise from the F...HN interaction, but rather from the CH...N interaction. The nucleobase analogue shows no inherent selectivity for adenine over other bases, and L-A pairing energies are slightly weaker than for F-A. Overall, the results are consistent with a small favorable noncovalent interaction of F with A offset by a large desolvation cost for the polar partner. We discuss the findings in light of recent structural studies and of DNA replication experiments involving these analogues. PMID- 22300090 TI - Prevalence and subtypes of BK virus in pediatric renal transplant recipients in Russia. AB - BKV reactivation is associated with impaired graft function in kidney transplant patients. The objective of our study was to determine the prevalence of BKV infection in consecutive pediatric kidney transplant recipients at our center. Fifty-eight pediatric kidney transplant recipients were studied. The mean age at screening was 9.4 +/- 2.8 yr, and samples were obtained at a median of 2.4 +/- 1.4 yr after transplantation. BKV-DNA was analyzed in urine and plasma by quantitative PCR. Occurrences of BK-DNAuria and BK-DNAemia did not change in the first two yr after transplantation in children and amounted to 21-23% and 7-8%, respectively (p > 0.05). In the third year, the occurrences of BK-DNAuria and BK DNAemia increased insignificantly to 27% and 9% in the pediatric patients. We also determined the subtypes and subgroups of BK virus isolated from Russian renal transplant recipients and found that BKV isolates were composed of subtypes Ib-2 and IV/c2. The data we obtained indicate that although only 5% of BKVAN cases occurred between years two and five post-transplantation, it seems necessary to regularly monitor pediatric patients for BKV infection through the third year after transplantation. PMID- 22300091 TI - Are pharmacokinetic approaches feasible for treatment of cocaine addiction and overdose? PMID- 22300092 TI - The dark side of pharmaceutical chemistry. PMID- 22300094 TI - Bacterial cocaine esterase: a protein-based therapy for cocaine overdose and addiction. AB - Cocaine is highly addictive and there are no pharmacotherapeutic drugs available to treat acute cocaine toxicity or chronic abuse. Antagonizing an inhibitor such as cocaine using a small molecule has proven difficult. The alternative approach is to modify cocaine's pharmacokinetic properties by sequestering or hydrolyzing it in serum and limiting access to its sites of action. We took advantage of a bacterial esterase (CocE) that has evolved to hydrolyze cocaine and have developed it as a therapeutic that rapidly and specifically clears cocaine from the subject. Native enzyme was unstable at 37 degrees C, thus limiting CocE's potential. Innovative computational methods based on the protein's structure helped elucidate its mechanism of destabilization. Novel protein engineering methodologies were applied to substantially improve its stability in vitro and in vivo. These improvements rendered CocE as a powerful and efficacious therapeutic to treat cocaine intoxication and lead the way towards developing a therapy for addiction. PMID- 22300095 TI - Cocaine hydrolase gene therapy for cocaine abuse. AB - Rapid progress in the past decade with re-engineering of human plasma butyrylcholinesterase has led to enzymes that destroy cocaine so efficiently that they prevent or interrupt drug actions in the CNS even though confined to the blood stream. Over the same time window, improved gene-transfer technology has made it possible to deliver such enzymes by endogenous gene transduction at high levels for periods of a year or longer after a single treatment. This article reviews recent advances in this field and considers prospects for development of a robust therapy aimed at aiding recovering drug users avoid addiction relapse. PMID- 22300096 TI - Accelerating cocaine metabolism as an approach to the treatment of cocaine abuse and toxicity. AB - One pharmacokinetic approach to the treatment of cocaine abuse and toxicity involves the development of compounds that can be safely administered to humans and that accelerate the metabolism of cocaine to inactive components. Catalytic antibodies have been developed and shown to accelerate cocaine metabolism, but their catalytic efficiency for cocaine is relatively low. Mutations of human butyrylcholinesterase and a bacterial cocaine esterase found in the soil of coca plants have also been developed. These compounds accelerate cocaine metabolism and antagonize the behavioral and toxic effects of cocaine in animal models. Of these two approaches, the human butyrylcholinesterase mutants show the most immediate promise as they would not be expected to evoke an immune response in humans. PMID- 22300097 TI - l-tetrahydropalamatine: a potential new medication for the treatment of cocaine addiction. AB - Levo-tetrahydropalmatine (l-THP) is an active constituent of herbal preparations containing plant species of the genera Stephania and Corydalis and has been approved and used in China for a number of clinical indications under the drug name Rotundine. The pharmacological profile of l-THP, which includes antagonism of dopamine D1 and D2 receptors and actions at dopamine D3, alpha adrenergic and serotonin receptors, suggests that it may have utility for treating cocaine addiction. In this review, we provide an overview of the pharmacological properties of l-THP and the evidence supporting its development as an anti addiction medication. The results of preclinical work demonstrating that l-THP attenuates cocaine's reinforcing/rewarding effects and reinstatement in rat models of cocaine relapse are summarized, and the outcomes of studies demonstrating efficacy in human addicts are described. Finally, an overview of the safety profile of l-THP is provided and challenges associated with US FDA approval of l-THP are discussed. PMID- 22300098 TI - Latest advances in novel cannabinoid CB(2) ligands for drug abuse and their therapeutic potential. AB - The field of cannabinoid (CB) drug research is experiencing a challenge as the CB(1) antagonist Rimonabant, launched in 2006 as an anorectic/anti-obesity drug, was withdrawn from the European market due to the complications of suicide and depression as side effects. There is interest in developing CB(2) drugs without CB(1) psychotropic side effects for drug-abuse treatment and therapeutic medication. The CB(1) receptor was discovered predominantly in the brain, whereas the CB(2) is mainly expressed in peripheral cells and tissues, and is involved in immune signal transduction. Conversely, the CB(2) receptor was recently detected in the CNS, for example, in the microglial cells and the neurons. While the CB(2) neurons activity remains controversial, the CB(2) receptor is an attractive therapeutic target for neuropathic pain, immune system, cancer and osteoporosis without psychoactivity. This review addresses CB drug abuse and therapeutic potential with a focus on the most recent advances on new CB(2) ligands from the literature as well as patents. PMID- 22300099 TI - Opioid glycopeptide analgesics derived from endogenous enkephalins and endorphins. AB - Over the past two decades, potent and selective analgesics have been developed from endogenous opioid peptides. Glycosylation provides an important means of modulating interaction with biological membranes, which greatly affects the pharmacodynamics and pharmacokinetics of the resulting glycopeptide analogues. Furthermore, manipulation of the membrane affinity allows penetration of cellular barriers that block efficient drug distribution, including the blood-brain barrier. Extremely potent and selective opiate agonists have been developed from endogenous peptides, some of which show great promise as drug candidates. PMID- 22300100 TI - Pharmacokinetic strategies for treatment of drug overdose and addiction. AB - The pharmacokinetic treatment strategy targets the drug molecule itself, aiming to reduce drug concentration at the site of action, thereby minimizing any pharmacodynamic effect. This approach might be useful in the treatment of acute drug toxicity/overdose and in the long-term treatment of addiction. Phase IIa controlled clinical trials with anticocaine and antinicotine vaccines have shown good tolerability and some efficacy, but Phase IIb and III trials have been disappointing because of the failure to generate adequate antibody titers in most participants. Monoclonal antibodies against cocaine, methamphetamine and phencyclidine have shown promise in animal studies, as has enhancing cocaine metabolism with genetic variants of human butyrylcholinesterase, with a bacterial esterase, and with catalytic monoclonal antibodies. Pharmacokinetic treatments offer potential advantages in terms of patient adherence, absence of medication interactions and benefit for patients who cannot take standard medications. PMID- 22300101 TI - Agonist replacement therapy for cocaine dependence: a translational review. AB - Cocaine use disorders are prevalent throughout the world. Agonist replacement therapy is among the most effective strategies for managing substance use disorders including nicotine and opioid dependence. This paper reviews the translational literature, including preclinical experiments, human laboratory studies and clinical trials, to determine whether agonist-replacement therapy is a viable strategy for managing cocaine dependence. Discussion is limited to transporter blockers (i.e., methylphenidate) and releasers (i.e., amphetamine analogs) that are available for use in humans in the hope of impacting clinical research and practice more quickly. The translational review suggests that agonist-replacement therapy, especially monoamine releasers, may be effective for managing cocaine dependence. Future directions for medications development are also discussed because the viability of agonist-replacement therapy for cocaine dependence may hinge on identifying novel compounds or formulations that have less abuse and diversion potential. PMID- 22300103 TI - Lung transplantation in patients with prior cardiothoracic surgical procedures. AB - The full spectrum of prior cardiothoracic procedures in lung transplant candidates and the impact of prior procedures on outcomes after lung transplantation (LTx) remain unknown, though the impact is considered to be large. Patients transplanted at our institution from 2004 to 2009 were identified (n = 554) and divided into two groups: patients who had undergone cardiothoracic surgical (CTS) procedures prior to LTx (n = 238) and patients who had not (non CTS: n = 316). Our primary endpoint was survival. Secondary endpoints included allograft function and the incidence of major complications including reexploration due to bleeding, prolonged ventilation, renal insufficiency and primary graft dysfunction. Long-term survival was not significantly different between the groups whereas postoperative bleeding, nerve injury, respiratory and renal complications were higher in the CTS group. Posttransplant peak FEV1 was lower in the CTS group (73.4% vs. 86.9%, p < 0.05). In multivariate analysis, performance of a chemical pleurodesis procedure and prolonged cardiopulmonary bypass were significantly associated with mortality (OR, 1.7; CI, 1.5-2.0; p < 0.005). Our results suggest that patients with LTx and prior CTS remain technically challenging and experience worse outcomes than patients without prior CTS. A surgical strategy to minimize cardiopulmonary bypass time is critical for these challenging LTx patients. PMID- 22300105 TI - Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice. AB - BACKGROUND AND PURPOSE: Cannabichromene (CBC) is a major non-psychotropic phytocannabinoid that inhibits endocannabinoid inactivation and activates the transient receptor potential ankyrin-1 (TRPA1). Both endocannabinoids and TRPA1 may modulate gastrointestinal motility. Here, we investigated the effect of CBC on mouse intestinal motility in physiological and pathological states. EXPERIMENTAL APPROACH: Inflammation was induced in the mouse small intestine by croton oil. Endocannabinoid (anandamide and 2-arachidonoyl glycerol), palmitoylethanolamide and oleoylethanolamide levels were measured by liquid chromatography-mass spectrometry; TRPA1 and cannabinoid receptors were analysed by quantitative RT-PCR; upper gastrointestinal transit, colonic propulsion and whole gut transit were evaluated in vivo; contractility was evaluated in vitro by stimulating the isolated ileum, in an organ bath, with ACh or electrical field stimulation (EFS). KEY RESULTS: Croton oil administration was associated with decreased levels of anandamide (but not 2-arachidonoyl glycerol) and palmitoylethanolamide, up-regulation of TRPA1 and CB1 receptors and down regulation of CB2 receptors. Ex vivo CBC did not change endocannabinoid levels, but it altered the mRNA expression of TRPA1 and cannabinoid receptors. In vivo, CBC did not affect motility in control mice, but normalized croton oil-induced hypermotility. In vitro, CBC reduced preferentially EFS- versus ACh-induced contractions. Both in vitro and in vivo, the inhibitory effect of CBC was not modified by cannabinoid or TRPA1 receptor antagonists. CONCLUSION AND IMPLICATIONS: CBC selectively reduces inflammation-induced hypermotility in vivo in a manner that is not dependent on cannabinoid receptors or TRPA1. PMID- 22300106 TI - Femoral head osteonecrosis after long-term topical corticosteroid treatment in a psoriasis patient. PMID- 22300107 TI - 3-(2,4-dimethoxybenzylidene)-anabaseine: a promising candidate drug for Alzheimer's disease? AB - 3-(2,4-dimethoxybenzylidene)-anabaseine is an analog of the paralytic alkaloid, anabaseine, from the ribbon worms Amphiporus sp., that shows numerous properties, in particular an agonist activity on alpha 7 nicotinic acetylcholine receptors. This article reviews these properties and explains to what extent they could be valuable to control symptomatology and/or neurodegeneration in Alzheimer's disease. PMID- 22300108 TI - Lack of C4d deposition may reveal susceptibility for ascending aortic dissection. AB - OBJECTIVES: Complement activation as evidenced by C4d deposition indicates immunological tissue reactivity. We sought to study the vascular reactivity of the aortic wall by characterizing C4d deposits. DESIGN: Aortic wall histology and immunohistochemistry for C4d, leukocytes, T- and B-lymphocytes, plasma cells, macrophages, endothelial cells, smooth muscle cells, cell proliferation, elastase, and Van-Gieson-staining were performed to 91 consecutive patients that underwent surgery for ascending aorta, and the samples were grouped according to presence of C4d deposits. RESULTS: Fifty-three out of 91 patients had C4d deposits mainly within the adventitia (C4d +), whereas 38 patients lacked C4d deposits (C4d-) including decreased staining of intra-aortic vessels (p < 0.005). Intimal thickness and cellularity, together with inflammation consisting of plasma cells were increased in C4d- as compared with C4d + (p < 0.05). Receiver operating characteristic curve (ROC) analysis showed that C4d was associated with stabile nondissecting ascending aorta (AUC 0.792; SE 0.053; p = 0.000; 95% CI 0.688-0.895), but not with presence of aortitis per se (AUC 0.523; SE 0.069; p = 0.752; 95 % CI 0.388-0.658). CONCLUSIONS: Lack of C4d may indicate active remodeling of the aortic wall leading to aortic dissection (AD). Immunologic complement factors may be amenable to diagnosis of instability after aortic surgery. PMID- 22300109 TI - Chromoendoscopy for H. pylori infection--time for a reaction? PMID- 22300110 TI - Chromoendoscopy with red phenol in the diagnosis of Helicobacter pylori infection. AB - An analytic study to validate a diagnostic test was carried out at the Institute of Gastroenterology in Havana, Cuba in adult patients of both sexes in whom chromoendoscopy was carried out with red phenol at 0.1% over the gastric mucosa for the detection of Helicobacter pylori infection between November 2008 and December 2010. The staining with red phenol at 0.1% is included in the invasive tests for the diagnosis of Helicobacter pylori infection and of the reactive techniques. The sensibility of red phenol dye in the diagnosis of Helicobacter pylori infection in the patients studied was of 72.6% with a confidence interval (C.I.) of 95% (64.9 to 79.2%) and a specificity of 75.5% C.I. 95% (61.9 to 85.4%). The positive predictive value was of 89.8% C.I. 95% (83.1 to 94.1%) and the negative predictive value of 48.1% C.I. 95% (37.3 to 59.0%). The proportion of false positives was of 24.5% C.I. 95% (14.6 to 38.1%)and the proportion of false negatives was of 27.4% C.I. 95% (20.8 to 35.1%). The diagnostic accuracy of the dye on the patients studied was 73.3% C.I. 95% (66.7 to 79.0%). The diagnostic odds ratio was 8.17 C.I. 95% (3.88 to 17.23), the J Youden ratio of 0.5 and the Kappa coefficient of 0.40 C.I. 95% (0.27 to 0.54). The staining dye with red phenol at 0.1% resulted in a useful method in the diagnosis of Helicobacter pylori infection in the gastric mucosa, it can be applied in our environment and has multiple advantages (topographic localization, avoids contamination and fast and immediate reading). PMID- 22300111 TI - Diagnostic incidence of the presence of positive HBsAg: epidemiologic, clinical, and virological characteristics. AB - OBJECTIVE: To analyze the epidemiological, clinical, and virological characteristics of patients newly diagnosed with active hepatitis B virus (HBV) infection based on the presence of positive hepatitis B surface antigen (HBsAg) in the digestive diseases department of a district hospital. PATIENTS AND METHODS: We performed a 3-year prospective study in patients newly diagnosed with HBV infection. We analyzed epidemiological, clinical, and virological characteristics, complete HBV markers, quantification of HBV DNA, and infection by hepatitis delta virus. We performed genotyping and resistance testing in patients with a high viral load. Results were obtained for patientswho required liver biopsy. RESULTS: We diagnosed 213 patients (18.8/10,000 inhabitants/year). Men accounted for 61%, and 59% were aged 20 to 40 years. Immigrants accounted for 53% of the population: 46% were from Rumania and 37% from Sub-Saharan African countries. At diagnosis, 2.3% had acute hepatitis (all with jaundice) and 3.3% had cirrhosis with portal hypertension. With the exception of cases of acute hepatitis, positive HBeAg was observed in 9%. Serum transaminase levels were normal in 62.2% of patients, HBV DNA was > 2,000 IU/mL in 33.8%, and delta virus was present in 3.3%. Genotyping and resistance testing were performed in 70 patients: the most common genotype was D, followed by A. Resistance was detected at baseline in only 2 cases: to adefovir in one case and to entecavir in another. Among the 36 biopsies performed, 32.4% showed inflammatory activity > or = 2, and 23.5% had fibrosis > or = 2 according to the METAVIR scoring system. According to clinical practice, specific treatment for HBV infection was necessary (any reason) in 17.4% of those diagnosed (3 patients per 100,000 inhabitants/year). CONCLUSIONS: Despite prevention and vaccination, HBV infection is a health problem that most commonly affects the immigrant population and men. Serum transaminase levels are normal in 62.2% of patients. The most frequent genotype is D, followed by A, and baseline resistance is scarce. PMID- 22300112 TI - Effect upon hospital activity of the application of a continued care model centered on patients with inflammatory bowel disease. AB - BACKGROUND: Since 1999, the Crohn-Colitis Care Unit (UACC) has been dedicated to the integral management of patients with Crohn's disease (CD) and ulcerative colitis (UC). The working methodology of the UACC is based on personalized, continued, nonphysical presence, open access and patient-centered care. From its creation, the UACC has experienced an increase in the number of its users and outpatient services. However, the impact of the activity of the UACC upon patient hospitalization is not known. OBJECTIVES: To determine the hospital activity related to CD and UC, and correlate it to the activity of the UACC. METHODS: A retrospective evaluation was made of the physical presence and non-presence activities of the UACC from January 1999 to December 2008, and of the hospital admissions and mean durations of stay due to CD and UC during that same time period. RESULTS: The number of attended patients and of presence and non-presence activities of the UACC has gradually increased. This increase contrasts with the number of annual hospital admissions, which has remained stable during the study period, with 200-300 admissions/year. Consequently, the hospitalized patients / UACC registered patients ratio has decreased from 0.36 at the start of the study period to 0.14 at the end. The median hospital stay has also decreased, from 11 days at the start of the study period to 8 days at the end. CONCLUSIONS: The UACC allows effective management of IBD patient care, since it is able to attend the needs of more patients without increasing the number of admissions, and shortening the duration of hospital stay. PMID- 22300113 TI - Acute hepatitis C in Spain: a retrospective study of 131 cases. AB - BACKGROUND AND AIMS: The management of acute hepatitis C (AHC) is controversial. We have conducted a retrospective study to determine the epidemiological and biochemical aspects, the genotypes, the spontaneous clearance of HCV (SVC), and the treatment responses in patients with AHC. METHODS: We have retrospectively collected data from 131 patients with AHC from 18 Spanish hospitals. RESULTS: The mean age was 43 +/- 16 years (17-83), 69% were symptomatic. The causes of infection were nosocomial in 40% and intravenous drug users in 20%. Eighty two percent had genotype 1. The delay from symptoms-onset to HCV-RNA confirmation was 50 +/- 68 days (range, 11-350 days) and to treatment (in 59%) 14+/-1 3 weeks (range, 2-58 days). In the treated group, 80% achieved sustained virological response (SVR) versus 57% SVC in untreated patients (p = 0.004). Up to 96% of those treated within the first 12 weeks had SVR versus 86% of those treated later (p = 0.04). Patients with HCV-RNA(-) at week 4 resolved with or without treatment more frequently than those HCV-RNA(+) (98% versus 69%, p = 0.005). The treatment was not beneficial if HCV-RNA was undetectable at week 12. No differences in SVR were found in genotype 1 patients treated for 24 or 48 weeks. Patients with low baseline viral load achieved higher SVC and SVR. The SVC in patients with bilirubin > 5 mg/dL was 78 versus 40% in those with lower values (p = 0.004). CONCLUSIONS: The most common transmission route was nosocomial. SVR was higher in patients treated than SVC in non-treated.Early treatment (before week 12) achieved the highest response rate. SVC and SVR were more common in patients with a low baseline viral load. Undetectable HCV-RNA at week 4 was associated with high SVR and SVC rates. Jaundice was related with SVC. PMID- 22300114 TI - Diagnostic protocol for pancreatic neuroendocrine tumors (PNETs). PMID- 22300115 TI - Upper gastrointestinal bleeding due to gastric and duodenal Kaposi's sarcoma. PMID- 22300116 TI - The endoscopic picture of upper digestive hemorrages secondary to stromal tumors (GIST): report of two cases. PMID- 22300117 TI - Recurrent small intestine intussusception in a patient with Peutz-Jeghers syndrome. AB - Peutz-Jeghers syndrome is a rare hereditary autosomal dominant disease caused by a mutation of the tumor suppressor gene serine/threonine kinase 11 located in chromosome 19p13.3. It is characterized by the presence of extensive mucocutaneous pigmentation, especially of the lips and the occurrence of hamartomatous polyps throughout the gastrointestinal tract. Gastrointestinal hamartomas occur predominantly in the small intestine and can become symptomatic leading usually to intestinal obstruction and abdominal pain.We present a case of recurrent intestinal obstruction caused by small bowel intussusception treated by reduction, enterotomy and polypectomy and followed by intraoperative enteroscopy and endoscopic polypectomy. PMID- 22300118 TI - [Use of clips in gastrointestinal endoscopy]. PMID- 22300119 TI - Perianal cutaneous metastases from colorectal adenocarcinoma. PMID- 22300120 TI - Empyema necessitatis in an elderly patient. A rare pathological entity in modern times. PMID- 22300121 TI - Mucinous appendiceal neoplasms. Do we all speak the same language? PMID- 22300122 TI - Idiopathic portal hypertension complicated by ischemic hepatitis: the diagnostic importance of hemodynamics and liver biopsy. PMID- 22300123 TI - Reply: Is there any association between proton pump inhibitors and fundic gland polyps? PMID- 22300125 TI - Complementary and alternative medicine in inflammatory bowel disease. PMID- 22300126 TI - The Fatigue Questionnaire has a good test-retest profile in IBD. PMID- 22300127 TI - Ursodeoxycholic acid in primary sclerosing cholangitis. PMID- 22300128 TI - Carl Friedrich Wilhelm Ludwig, a fabled physiologist and mentor of Scandinavian Physiology Announcing the Carl Ludwig Award for young authors in Acta Physiologica (Oxford). PMID- 22300129 TI - Getting a kick out of thermoregulation. PMID- 22300130 TI - Effects of high temperature on desolvation costs of salt bridges across protein binding interfaces: similarities and differences between implicit and explicit solvent models. AB - The role of salt bridges in protein-protein binding is largely determined by the costs of desolvating the oppositely charged members of the salt bridge upon binding. On the basis of Poisson-Boltzmann (PB) implicit solvent calculations, it has been proposed that the reduced desolvation penalties of salt bridges at high temperatures provide one explanation for the increased abundance of salt bridges in hyperthermophilic proteins. Here, for the first time, we directly compare the PB implicit solvent model with several explicit water models in computing the effects of extremely high temperature (i.e., 100 degrees C) on the desolvation penalties of salt bridges across protein-protein interfaces. With the exception of two outliers, the desolvation costs at 100 degrees C from implicit and explicit solvent calculations are of similar magnitudes and significantly reduced relative to 25 degrees C. The two outliers correspond to salt bridges that are both buried and part of a salt bridge network, a challenging case that should be considered in the development of fast solvation models. PMID- 22300131 TI - Left anterior descending coronary artery pseudoaneurysm compressing the main pulmonary artery in a patient with Behcet's disease. AB - Behcet's disease is a systemic inflammatory vascular disorder that may affect the cardiovascular system. Left anterior descending (LAD) artery aneurysm is a rare but potentially fatal complication of Behcet's disease. An accurate diagnosis of this clinical entity requires multimodal imaging (computerized tomography, angiography, and echocardiography) and is essential to guide appropriate therapeutic management. We report the case of a 22-year-old female with LAD pseudoaneurysm who underwent surgical repair with transesophageal echocardiography guidance. We describe the importance of the use of an alternative view to define the origin and location of this unusual pathology. PMID- 22300132 TI - Infrared multiple photon dissociation spectroscopy and computational studies of O glycosylated peptides. AB - The infrared multiple photon dissociation (IRMPD) spectra of O-glycosylated peptides in the gas phase were studied in the IR scanning range of 5.7-9.5 MUm. Fragmentation of protonated and sodiated O-glycopeptides was investigated using electrospray ionization (ESI) Fourier-transform ion cyclotron resonance (FTICR) mass spectrometry (MS) with a free electron laser (FEL). FEL is used in the IRMPD technique as a tunable IR light source. In the IRMPD spectroscopic analysis of the protonated O-glycopeptide, fragment ions of the b/y and B/Y types were observed in the range of 5.7-9.5 MUm, corresponding to the cleavage of the backbone in the parent amino acid sequence and glycosyl bonds, whereas the spectra of the sodiated glycopeptide showed major peaks of photoproducts of the B/Y type in the range of 8.4-9.5 MUm. The IRMPD spectra of the O-glycopeptides were compared with simulated IR spectra for the structures obtained from the molecular dynamics. PMID- 22300133 TI - Recruiting women with breast cancer in rural communities for a community initiated clinical trial: effective strategies. PMID- 22300134 TI - BCR/ABL1 fusion transcripts generated from alternative splicing: implications for future targeted therapies in Ph+ leukaemias. AB - Philadelphia (Ph+) positive leukaemias are an example of haematological malignant diseases where different chromosomal rearrangements involving both BCR and ABL1 genes generate a variety of chimeric proteins (BCR/ABL1 p210, p190 and p230) which are considered pathological "biomarkers". In addition to these three, there is a variety of fusion transcripts whose origin may depend either on diverse genetic rearrangement or on alternative/atypical splicing of the main mRNAs or on the occurrence of single-point mutations. Although the therapy of Ph+ leukaemias based on Imatinib represents a triumph of medicine, not all patients benefit from such drug and may show resistance and intolerance. Furthermore, interruption of Imatinib administration is often followed by clinical relapse, suggesting a failure in the eradication of residual leukaemic stem cells. Therefore, while the targeted therapy is searching for new and implemented pharmacological inhibitors covering all the possible mutations in the kinase domain, there is urge to identify alternative molecular targets to develop other specific and effective therapeutic approaches. In this review we discuss the importance of recent advances based on the discovery of novel BCR/ABL1 variants and their potential role as new targets/biomarkers of Ph+ leukaemias in the light of the current therapeutic trends. The limits of the pharmacological inhibitors used for treating the disease can be overcome by considering other targets than the kinase enzyme. Our evaluations highlight the potential of alternative perspectives in the therapy of Ph+ leukaemias. PMID- 22300135 TI - Recent advances in GNAS epigenetic research of pseudohypoparathyroidism. AB - Endocrinopathies in patients with hypocalcemia and hyperphosphatemia that share resistance to parathyroid hormone (PTH) are grouped under the term pseudohypoparathyroidism (PHP). Patients with PHP type Ia (PHP-Ia) often present with additional hormonal resistance and show characteristic physical features that are jointly termed as having an Albright's hereditary osteodystrophy (AHO) phenotype. Alternatively, PHPIb patients predominantly have PTH and sometimes TSH resistance but do not present with AHO features. Most of these PHP forms are caused by defects in GNAS, an imprinted gene locus consisting of maternal, paternal and biallelic transcripts. PHP-Ia is caused by heterozygous inactivating mutations in those exons of GNAS encoding the alpha subunit of the stimulatory guanine nucleotide-binding protein (Gsalpha) while PHPIb results from epigenetic GNAS defects. Familial and sporadic forms of PHP-Ib have distinct GNAS imprinting patterns: familial PHP-Ib patients have an exon A/B-only imprinting defect whereas sporadic PHP-Ib cases have abnormal imprinting of the three differentially methylated regions (DMRs) in GNAS. This classification of PHP was made years ago but was recently questioned since different studies showed GNAS epigenetic defects in PHP-Ia patients. In this review, we focus on the epigenetic description and screening methods of GNAS, the associated pathology and the recent need for a PHP reclassification. PMID- 22300137 TI - The PD-1/PD-L1 pathway in human pathology. AB - T-cell activation is dependent on signals delivered through the antigen-specific T-cell receptor and accessory receptors on T-cells. Integration of signals through this family of costimulatory and inhibitory receptors and their ligands regulates the balance between T-cell activation, tolerance, and immunopathology. Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, deliver inhibitory signals and exert a vital and diverse range of immunoregulatory roles in T-cell activation, tolerance, and immune-mediated tissue damage. In this review, we revisit current understanding of the immunoregulatory functions of PD-1 and its ligands and their involvement in immune-mediated diseases. PMID- 22300136 TI - AAV-mediated gene therapy in mouse models of recessive retinal degeneration. AB - In recent years, more and more mutant genes that cause retinal diseases have been detected. At the same time, many naturally occurring mouse models of retinal degeneration have also been found, which show similar changes to human retinal diseases. These, together with improved viral vector quality allow more and more traditionally incurable inherited retinal disorders to become potential candidates for gene therapy. Currently, the most common vehicle to deliver the therapeutic gene into target retinal cells is the adenoassociated viral vector (AAV). Following delivery to the immuno-privileged subretinal space, AAV-vectors can efficiently target both retinal pigment epithelium and photoreceptor cells, the origin of most retinal degenerations. This review focuses on the AAV-based gene therapy in mouse models of recessive retinal degenerations, especially those in which delivery of the correct copy of the wild-type gene has led to significant beneficial effects on visual function, as determined by morphological, biochemical, electroretinographic and behavioral analysis. The past studies in animal models and ongoing successful LCA2 clinical trials, predict a bright future for AAV gene replacement treatment for inherited recessive retinal diseases. PMID- 22300138 TI - Emerging roles of microRNA-22 in human disease and normal physiology. AB - MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs that have critical regulatory functions in various biological processes. MicroRNA-22 (miR 22) is a highly-conserved 22-nt miRNA, whose roles in human diseases and normal physiology are just beginning to emerge. Recently, miR-22 has been connected to a great number of activities that encompass tumorigenesis, epigenetic modification, embryonic development, skeletal metabolism, panic disorder, and cardiomyocyte hypertrophy. Aberrant expression of miR-22 has been identified in multiple human diseases. Here, we describe our current understanding of the roles of miR-22 and its signaling circuitry in pathology and physiology, and discuss important advances that set the scene for applying miR-22 to the prevention and treatment of a wide range of human diseases. PMID- 22300139 TI - The role and therapeutic potential of Ser/Thr phosphatase PP2A in apoptotic signalling networks in human cancer cells. AB - A block in apoptotic cell death is a likely requirement for cancer maintenance. Likewise, drug resistance, one of the key clinical problems in oncology, can often be explained by apoptotic resistance following drug administration. Several signalling pathways can commit cells to death, including intrinsic mitochondrial pathways controlled by the Bcl-2-like proteins, extrinsic Death Receptor triggered pathways, and Dependence Receptor-initiated pathways. In addition, depending on the cell type, external stimulus and context, various other pro- or anti-survival signalling pathways may become repressed or activated. Proper coordination and conversion into a common cellular response is ensured by various ways of inter-pathway crosstalk. As for most signalling cascades, post translational control of the signalling proteins involved is mainly achieved by reversible phosphorylation and thus by the coordinated actions of protein kinases and phosphatases. Despite increasing interest in phosphatases as potential tumour suppressors, their role in controlling apoptotic signalling remains poorly understood. Here we review current knowledge about the regulatory functions of Protein Phosphatase type 2A (PP2A) phosphatases in these apoptotic signalling networks. PP2A represents an abundant class of structurally complex Ser/Thr phosphatases which are of particular interest in this context because of their recently established role as genuine tumour suppressors. In line with these tumour suppressive characteristics, PP2A predominantly displays pro-apoptotic functions, although some PP2A complexes also clearly counteract apoptotic cell death. Finally, we speculate how this knowledge might be exploited for therapeutic purposes, in light of pre-clinical pharmacological approaches, currently demonstrated to target PP2A in cancer cells. PMID- 22300142 TI - Editorial. toxic chemicals in surface waters. PMID- 22300140 TI - The association between leisure-time physical activities and asthma symptoms among 10- to 12-year-old children: the effect of living environment in the PANACEA study. AB - OBJECTIVE: This study evaluated the interrelationships of living environment, physical activity, lifestyle/dietary habits, and nutritional status on the prevalence of childhood asthma. METHODS: In a cross-sectional survey 1125 children (529 boys), 10 to 12 years old, were selected from 18 schools located in an urban environment (Athens, n = 700) and from 10 schools located in rural areas (n = 425) in Greece. RESULTS: Children living in Athens had higher likelihood of "ever had" asthma compared with children living in rural areas (odds ratio (OR) = 1.78, 95% confidence interval (CI) = 1.25-2.54), after adjusting for age and sex. After adjusting for age, sex, body mass index, and adherence to the Mediterranean diet (KIDMED score), leisure-time physical activity was inversely associated with "ever had" asthma. When stratifying by county of residence, a trend toward reduced asthma symptoms among children engaged in outdoor physical activities during their leisure time who reside in rural (but not urban) environment was observed (OR = 0.88, 95% CI = 0.77-1.01). CONCLUSIONS: The inverse relationship between asthma symptoms and leisure-time physical activity in the rural environment and the lack of an association between asthma symptoms and organized sports-related activities should draw the attention of public healthcare authorities. Their efforts should focus on the planning of a sustainable natural environment, which will promote the physical health of children and reduce the burden of childhood asthma. PMID- 22300143 TI - Currents. PMID- 22300144 TI - Airborne toxic elements and organic substances. PMID- 22300145 TI - Waste monitoring. PMID- 22300146 TI - Regulatory Focus: EPA drinking-water proposals: Round two. PMID- 22300147 TI - ES Views: Implementing Superfund. PMID- 22300148 TI - Implications of a gradient in acid and ion deposition across the northern Great Lakes states. PMID- 22300149 TI - Application of mass-transfer theory to the kinetics of a fast gas-liquid reaction: chlorine hydrolysis. PMID- 22300150 TI - Kinetics of the reaction between molecular chlorine and chlorite in aqueous solution. PMID- 22300151 TI - Effects of nonreversibility, particle concentration, and ionic strength on heavy metal sorption. PMID- 22300152 TI - Vertical transport processes of an acid-iron waste in a MERL stratified mesocosm. PMID- 22300154 TI - Products and quantum yields for photolysis of chloroaromatics in water. PMID- 22300153 TI - Aromatic hydrocarbons in New York Bight polychaetes: ultraviolet fluorescence analyses and gas chromatography/gas chromatography-mass spectrometry analyses. PMID- 22300155 TI - A comparative study of combustion in kerosine heaters. PMID- 22300156 TI - Photochemical transformation of pyrene and benzo[a]pyrene vapor-deposited on eight coal stack ashes. PMID- 22300157 TI - Contribution of Gulf area natural sulfur to the North American sulfur budget. PMID- 22300158 TI - Sequential dehalogenation of chlorinated ethenes. PMID- 22300159 TI - Perfluorocarbon measurement using an automated dual-trap analyzer. PMID- 22300161 TI - Combined theoretical and experimental study on high diastereoselective chirality transfer based on [2.2]paracyclophane derivative chiral reagent. AB - We report a paracyclophane N-Me thioamide chiral reagent for the asymmetric thio Claisen rearrangement with high diasteroselectivity. Comparisons between candidate chiral reagent N-phenyl-N-([2.2]paracyclophan-4-yl)amide, N-methyl amide, N-phenyl thioamide, and N-methyl thioamide are made both by experiment and theoretical calculations to clarify the principle behind the high diasteroselectivity. Dynamic (1)H NMR phenomenon tested by varying temperature (VT) experiments has proved that N-Ph amides have triple splitting peaks, while N Ph thioamide would reduce the number to two, further substituting the Ph to Me made dynamic phenomenon disappear. So the side chain is thought to be the most rigid in N-Me thioamide, which accounts for a structure prerequisite favoring high efficient chirality transfer. This is confirmed by theoretical calculation: remarkable energy difference exists between the Re and Si faces of the chiral molecule. To further clarify the possible pathways for thio-Claisen rearrangement, theoretical prediction is adopted. The result implies that the cisoid pathways will dominate the process. Further experiment confirmed this: with N-Me thioamide, the asymmetrical reaction affords gamma-unsaturated thioamides in good yields and high diastereoselectivities up to 98%. After removing the thioamide auxiliaries under hydrolysis conditions, product beta,gamma-substituted chiral alcohols reached high enantiopurity of 98% ee. PMID- 22300160 TI - Subcutaneous adipose tissue fatty acid desaturation in adults with and without rare adipose disorders. AB - BACKGROUND: Elevated stearoyl-CoA desaturase activity has been described in obese states, with an increased desaturation index (DI) suggesting enhanced lipogenesis. Differences in the DI among various phenotypes of abnormal adiposity have not been studied. Abnormal accumulation of subcutaneous adipose tissue occurs in rare adipose disorders (RADs) including Dercum's disease (DD), multiple symmetric lipomatosis (MSL), and familial multiple lipomatosis (FML). Examining the DI in subcutaneous fat of people with DD, MSL and FML may provide information on adipose tissue fatty acid metabolism in these disorders. The aims of this pilot study were: 1) to determine if differences in adipose tissue DIs are present among RADs, and 2) to determine if the DIs correlate to clinical or biochemical parameters. METHODS: Subcutaneous adipose tissue was obtained from human participants with DD (n = 6), MSL (n = 5), FML (n = 8) and obese Controls (n = 6). Fatty acid composition was determined by gas chromatography/mass spectrometry. The DIs (palmitoleic/palmitic, oleic/stearic, vaccenic/stearic ratios) were calculated from the gas chromatogram peak intensities. SCD1 gene expression was determined. Spearman's correlations between the DIs and available clinical or biochemical data were performed. RESULTS: In DD subjects, the vaccenic/stearic index was lower (p < 0.05) in comparison to Controls. Percent of total of the saturated fatty acid myristic acid was higher in DD compared with Controls and FML. Percent of monounsaturated vaccenic acid in DD trended lower when compared with Controls, and was decreased in comparison to FML. In MSL, total percent of the polyunsaturated fatty acids was significantly lower than in the Control group (p < 0.05). In the total cohort of subjects, the palmitoleic/palmitic and oleic/stearic DIs positively correlated with age, BMI, and percent body fat. CONCLUSIONS: The positive associations between the DIs and measures of adiposity (BMI and percent body fat) support increased desaturase activity in obesity. The lower vaccenic/stearic DI in DD SAT compared with Controls suggests presence of other factors involved in fat accumulation in addition to lifestyle. Other mechanisms driving fat accumulation in DD such as inflammation or lymphatic dysfunction should be investigated. PMID- 22300162 TI - Effects of refractive index solutions on the color of different luting cements. AB - PURPOSE: The purpose of this study is to determine the effects of refractive index solutions on the color of different luting cements at different periods. MATERIALS AND METHODS: Fourteen disc-shaped specimens were prepared for three different universal shade luting cements. All specimens were divided into two groups and a phthalate ester and glycerol refractive index solution was applied to the specimens at different periods. Color differences (DeltaE*) were calculated for before and after 5, 15, 60 min and 24 h periods of applying refractive index solutions. Data were analyzed with multiple analysis of variance (ANOVA) and mean values were compared by the Tukey HSD test (alpha = 0.05). RESULTS: Periods and periods-cement interaction were statistically significant (p <= 0.05). There was no statistically significant difference between the mean DeltaE values of refractive index solutions and cement groups (p > 0.05). CONCLUSION: Refractive index solutions affected the color of luting cements. PMID- 22300163 TI - Multiple nodules in a linear pattern on the leg. PMID- 22300164 TI - Fish endocrine disruption responses to a major wastewater treatment facility upgrade. AB - The urban-water cycle modifies natural stream hydrology, and domestic and commercial activities increase the burden of endocrine-disrupting chemicals, such as steroidal hormones and 4-nonylphenol, that can disrupt endocrine system function in aquatic organisms. This paper presents a series of integrated chemical and biological investigations into the occurrence, fate, and effects of endocrine-disrupting chemicals in the City of Boulder Colorado's WWTF and Boulder Creek, the receiving stream. Results are presented showing the effects of a full scale upgrade of the WWTF (that treats 0.6 m(3) s(-1) of sewage) from a trickling filter/solids contact process to an activated sludge process on the removal of endocrine-disrupting compounds and other contaminants (including nutrients, boron, bismuth, gadolinium, and ethylenediaminetetraacetic acid) through each major treatment unit. Corresponding impacts of pre- and postupgrade effluent chemistry on fish reproductive end points were evaluated using on-site, continuous-flow experiments, in which male fathead minnows (Pimephales promelas) were exposed for 28 days to upstream Boulder Creek water and WWTF effluent under controlled conditions. The upgrade of the WWTF resulted in improved removal efficiency for many endocrine-disrupting chemicals, particularly 17beta-estradiol and estrone, and fish exposed to the postupgrade effluent indicated reduction in endocrine disruption relative to preupgrade conditions. PMID- 22300166 TI - Quantifying millisecond exchange dynamics in proteins by CPMG relaxation dispersion NMR using side-chain 1H probes. AB - A Carr-Purcell-Meiboom-Gill relaxation dispersion experiment is presented for quantifying millisecond time-scale chemical exchange at side-chain (1)H positions in proteins. Such experiments are not possible in a fully protonated molecule because of magnetization evolution from homonuclear scalar couplings that interferes with the extraction of accurate transverse relaxation rates. It is shown, however, that by using a labeling strategy whereby proteins are produced using {(13)C,(1)H}-glucose and D(2)O a significant number of 'isolated' side chain (1)H spins are generated, eliminating such effects. It thus becomes possible to record (1)H dispersion profiles at the beta positions of Asx, Cys, Ser, His, Phe, Tyr, and Trp as well as the gamma positions of Glx, in addition to the methyl side-chain moieties. This brings the total of amino acid side-chain positions that can be simultaneously probed using a single (1)H dispersion experiment to 16. The utility of the approach is demonstrated with an application to the four-helix bundle colicin E7 immunity protein, Im7, which folds via a partially structured low populated intermediate that interconverts with the folded, ground state on the millisecond time-scale. The extracted (1)H chemical shift differences at side-chain positions provide valuable restraints in structural studies of invisible, excited states, complementing backbone chemical shifts that are available from existing relaxation dispersion experiments. PMID- 22300167 TI - Development of PCR primers and a DNA macroarray for the simultaneous detection of major Staphylococcus species using groESL gene. AB - Staphylococcus spp., including S. aureus, S. intermedius, S. hyicus, S. epidermidis, S. saprophyticus, S. haemolyticus, S. xylosus, and S. carnosus, are major bacterial species associated with food poisoning, and human and veterinary clinics. Traditional methods for the identification of these staphylococci are time-consuming, laborious, or inaccurate. Therefore, rapid and accurate diagnostic methods are needed. In this study, we designed the DNA probes and polymerase chain reaction (PCR) primers for the detection of the aforementioned Staphylococcus species. These primers were proved to be specific for the detection of their corresponding target strains. Furthermore, by using a consensus primer pair, we were able to co-amplify the intergenic region of groES groEL for these staphylococci. Followed by a chromogenic macroarray system with the specific probes on the plastic chips, these staphylococci in milk products or clinical samples could be simultaneously detected. When the system was used for the inspection of milk or urine samples containing N * 100 target cells per milliliter of the sample, all these staphylococcal species could be identified after an 8-h pre-enrichment step. This system also allowed the adequate diagnosis of bacteremia, since N * 100 target cells per milliliter of the blood samples could be detected after a 12-h pre-enrichment. Compared to the multiplex PCR method, this approach has the additional advantage that it allowed the discrimination of more bacterial strains-even some bacterial strains that may generate PCR products with the same molecular sizes. PMID- 22300168 TI - Does terfenadine-induced ventricular tachycardia/fibrillation directly relate to its QT prolongation and Torsades de Pointes? AB - BACKGROUND AND PURPOSE: Terfenadine has been reported to cause cardiac death. Hence, we investigated its pro-arrhythmic potential in various in vitro models. EXPERIMENTAL APPROACH: Pro-arrhythmic effects of terfenadine were investigated in rabbit isolated hearts and left ventricular wedge preparations. Also, using whole cell patch-clamp recording, we examined its effect on the human ether-a-go-go related gene (hERG) current in HEK293 cells transfected with hERG and on the I(Na) current in rabbit ventricular cells and human atrial myocytes. KEY RESULTS: Terfenadine concentration- and use-dependently inhibited I(Na) in rabbit myocytes and in human atrial myocytes and also inhibited the hERG. In both the rabbit left ventricular wedge and heart preparations, terfenadine at 1 uM only slightly prolonged the QT- and JT-intervals but at 10 uM, it caused a marked widening of the QRS complex, cardiac wavelength shortening, incidences of in-excitability and non-TdP-like ventricular tachycardia/fibrillation (VT/VF) without prolongation of the QT/JT-interval. At 10 uM terfenadine elicited a lower incidence of early afterdepolarizations versus non- Torsades de Pointes (TdP)-like VT/VF (100% incidence), and did not induce TdPs. Although the concentration of terfenadine in the tissue-bath was low, it accumulated within the heart tissue. CONCLUSION AND IMPLICATIONS: Our data suggest that: (i) the induction of non-TdP-like VT/VF, which is caused by slowing of conduction via blockade of I(Na) (like Class Ic flecainide), may constitute a more important risk for terfenadine-induced cardiac death; (ii) although terfenadine is a potent hERG blocker, the risk for non-TdP like VT/VF exceeds the risk for TdPs; and (iii) cardiac wavelength (lambda) could serve as a biomarker to predict terfenadine-induced VT/VF. PMID- 22300169 TI - Immunological detection of osteocalcin in meat and bone meal: a novel heat stable marker for the investigation of illegal feed adulteration. AB - A sandwich ELISA was developed for the detection of bovine meat and bone meal (BMBM) in feed, based on polyclonal rabbit antibodies raised against the synthetic N-terminal amino acid sequence 1-9 (YLDHWLGAP) of bovine osteocalcin. To set up a sandwich ELISA pair, a commercial mouse monoclonal capture antibody binding to a highly conserved epitope in the mid-fragment of the peptide was employed. It is shown that the bone marker osteocalcin is immunologically well detectable in BMBM extracts obtained by a simple EDTA-based procedure even in a sample heated up to 145 degrees C. Furthermore, a genus-specific restriction of the major specificity to cattle and horse was possible. The observed bi specificity is consistent with theoretical predictions. The assay sensitivity with bovine osteocalcin of 1 ng was sufficient to enable the detection of 0.1% BMBM in compound plant feed or fish meal, for which no cross reaction was observed. In general the quantification of osteocalcin in extracts is possible using a standard curve procedure with pure bovine osteocalcin. PMID- 22300170 TI - Cytopathology of cervical mesonephric adenocarcinoma: a report of two cases. PMID- 22300171 TI - Blaschkitis-like eruptions with hypodontia and low IkappaB kinase gamma expression. PMID- 22300173 TI - Re'COG'nition at the Golgi. AB - The conserved oligomeric Golgi (COG) complex co-ordinates retrograde vesicle transport within the Golgi. These vesicles maintain the distribution of glycosylation enzymes between the Golgi's cisternae, and therefore COG is intimately involved in glycosylation homeostasis. Recent years have greatly enhanced our knowledge of COG's composition, protein interactions, cellular function and most recently also its structure. The emergence of COG-dependent human glycosylation disorders gives particular relevance to these advances. The structural data have firmly placed COG in the family of multi-subunit tethering complexes that it shares with the exocyst, Dsl1 and Golgi-associated retrograde protein (GARP) complexes. Here, we review our knowledge of COG's involvement in vesicle tethering at the Golgi. In particular, we consider what this knowledge may add to our molecular understanding of vesicle tethering and how it impacts on the fine tuning of Golgi function, most notably glycosylation. PMID- 22300172 TI - Early metabolic markers that anticipate loss of insulin independence in type 1 diabetic islet allograft recipients. AB - The objective of this study was to identify predictors of insulin independence and to establish the best clinical tools to follow patients after pancreatic islet transplantation (PIT). Sequential metabolic responses to intravenous (I.V.) glucose (I.V. glucose tolerance test [IVGTT]), arginine and glucose-potentiated arginine (glucose-potentiated arginine-induced insulin secretion [GPAIS]) were obtained from 30 patients. We determined the correlation between transplanted islet mass and islet engraftment and tested the ability of each assay to predict return to exogenous insulin therapy. We found transplanted islet mass within an average of 16 709 islet equivalents per kg body weight (IEQ/kg BW; range between 6602 and 29 614 IEQ/kg BW) to be a poor predictor of insulin independence at 1 year, having a poor correlation between transplanted islet mass and islet engraftment. Acute insulin response to IVGTT (AIR(GLU) ) and GPAIS (AIR(max) ) were the most accurate methods to determine suboptimal islet mass engraftment. AIR(GLU) performed 3 months after transplant also proved to be a robust early metabolic marker to predict return to insulin therapy and its value was positively correlated with duration of insulin independence. In conclusion, AIR(GLU) is an early metabolic assay capable of anticipating loss of insulin independence at 1 year in T1D patients undergoing PIT and constitutes a valuable, simple and reliable method to follow patients after transplant. PMID- 22300175 TI - Both conventional indices of cognitive function and frailty predict levels of care required in a long-term care insurance program for memory clinic patients in Japan. AB - AIM: To delineate relationships among cognitive function, frailty and level of care required in the Japanese long-term care insurance program (LTCIP) in outpatient memory clinic patients. METHODS: This was a cross-sectional study carried out at an outpatient memory clinic. Participants were 201 cognitively impaired patients. Cognitive function was measured by the Mini-Mental State Examination (MMSE). Frailty was measured by Timed Up & Go (TUG) and grip strength. Waist circumference, body mass index, living arrangement and level of care required in the LTCIP (rank 1 minor disability to rank 7 severe disability) were also assessed. RESULTS: Mean age, MMSE score, TUG score and grip strength were 78.8 +/- 6.9 years, 19.6 +/- 6.1, 14.6 +/- 6.7 s and 16.9 +/- 7.5 kg, respectively. A total of 70 patients (34.8%) had not applied for the certification, at least in part because of their younger age and existence of family caregivers. LTCIP rank was correlated both with MMSE score (beta: -0.49, P = 0.001), grip strength (beta: -0.27, P = 0.005) and living alone (beta: -0.18, P = 0.03), but not with TUG score (beta: 0.14, P = 0.105). CONCLUSION: In outpatients of a memory clinic, care ranks, which define the upper limit of monthly benefit in the Japanese LTCIP, were influenced by age, cognitive function, frailty and living arrangements. Understanding the relationship among these parameters would be useful in predicting the needs of cognitively impaired patients and important when comparing the possible services provided by long-term care systems for them worldwide. PMID- 22300177 TI - Metabolic syndromes. PMID- 22300176 TI - Ethnic group differences in the relationship between depressive symptoms and smoking. AB - OBJECTIVES: A relationship between depression and smoking has been documented; however, little attention has focused on ethnic variability in how this relationship is manifested. Thus, we examined the interaction between ethnicity and significant depressive symptoms on smoking status. DESIGN: A random digit dial survey (Minnesota Needs Assessment Survey) that oversampled ethnic minorities assessed demographics, smoking status, and depressive symptoms (Patient Health Questionnaire-2 [PHQ-2]). We examined the prevalence of current smoking between individuals with and without depressive symptoms within ethnic group and the interaction of depressive symptoms by ethnic group on smoking status. RESULTS: Of 16,981 participants, 20.8% were current smokers, and 7.7% reported significant depressive symptoms on the PHQ-2 (score >=3). Ethnic differences were observed in smoking rates (Asians 17.2%, Latinos 19.0%, whites 20.4%, African-Americans 23.4%, American Indians 51.2%) and depressive symptoms (Asians 4.9%, Latinos 13.1%, whites 7.0%, African-Americans 19.1%, American Indians 12.5%). Depressive symptoms were associated with a higher prevalence of smoking among Whites (34.5% vs. 19.4%), African-Americans (43.6% vs. 18.9%), and American Indians (81.9% vs. 47.1%), but not among Latinos (14.5% vs. 19.7%) or Asians (19.6% vs. 17.1%). The interaction between ethnicity and depressive symptomatology on current smoking was significant (p=0.02) among Latinos relative to Whites, controlling for other demographics. CONCLUSION: The relationship between depressive symptoms and smoking differs by ethnicity, particularly for Latinos. Understanding these differences may contribute to the development of culturally specific interventions. PMID- 22300179 TI - A 2-year-old male with pneumonia. PMID- 22300180 TI - A 10-year-old girl with fever and labored breathing. PMID- 22300181 TI - The possible link between gynecomastia, topical lavender, and tea tree oil. PMID- 22300182 TI - Metabolic disorders in the pediatric population. PMID- 22300183 TI - The importance of nutrition and physical activity for children. PMID- 22300184 TI - Transitions from adolescent to adult care. PMID- 22300185 TI - Pediatric oncology: "an area of great change". PMID- 22300186 TI - Helping patients achieve lifestyle change. PMID- 22300187 TI - A conversation with Richard F. Jacobs, MD, FAAP. Interview by Stanford T. Shulman. PMID- 22300188 TI - Molecular packing and lateral interactions of distearoylphosphatidylcholine with dihexadecyldimethylammonium bromide in Langmuir monolayers and vesicles. AB - The behavior of distearoylphosphatidylcholine (DSPC) mixed with dihexadecyldimethylammonium bromide (DHDAB) in the monolayer was investigated by means of Langmuir trough, interfacial thermodynamic analysis, and Brewster angle microscopy. It was found that the cationic surfactant, DHDAB, was miscible with DSPC and a condensing effect, indicating stronger contraction of area per molecule and stronger ordering molecular packing, appeared in the mixed DSPC/DHDAB monolayers. Condensed structures of the mixed monolayers were visible as the molar fraction of DHDAB (X(DHDAB)) <= 0.7. The negative deviations of excess area and mixing Gibbs free energy were obtained, and their minimum values occurred at X(DHDAB) = 0.3, suggesting that a DSPC/DHDAB monolayer with this composition exhibited the most pronounced intermolecular interactions with a compact molecular arrangement than the monolayers with separation between individual components. Furthermore, characteristics of mixed DSPC/DHDAB vesicles dispersed in water were studied by dynamic light scattering, transmission electron microscopy, and fluorescence polarization. The DSPC vesicles added with DHDAB showed zeta potentials of about +50 mV and narrower size distributions than those of pure DSPC vesicles. DSPC formed more rigid membranes than DHDAB, and the minimum disordering effect on membrane packing of vesicles was found at X(DHDAB) = 0.5, which was the most stable vesicle composition against aggregation. By contrast, the condensing effect and the increase of intermolecular attraction in mixed DSPC/DHDAB monolayers may be related to the stability enhancement of mixed vesicles as compared with the stability of pure component vesicles. PMID- 22300189 TI - MALDI imaging and structural analysis of rat brain lipid negative ions with 9 aminoacridine matrix. AB - Mass spectrometry imaging is of growing interest for chemical mapping of lipids at the surface of tissue sections. Many efforts have been devoted to optimize matrix choice and deposition technique for positive ion mode analyses. The identification of lipid species desorbed from tissue sections in the negative mode can be significantly improved by using 9-aminoacridine together with a robust deposition method, yielding a superior signal-to-noise ratio and thus a better contrast for the ion images in comparison to classical matrices such as alpha-cyano-4-hydroxycinnamic acid, 2,5-dihydroxybenzoic acid, or 2,4,6 trihydroxyacetophenone. Twenty-eight different lipid species (phosphatidic acids, phosphatidylethanolamines, phosphatidylserines, phosphatidylglycerols, phosphatidylinositols, phosphatidylinositol-phosphates, and sulfatides) were scrutinized on rat brain tissue sections, and systematic MS/MS studies were conducted. It was possible to identify isobaric species differing by their fatty acid chains thanks to the improved sensitivity. PMID- 22300191 TI - Dental injury and its prevention in Swiss rugby. AB - OBJECTIVES: Rugby players are at a high risk of sustaining dental injury because of the high number of tackles implicit to the game. This study aimed to determine the frequency of injuries sustained by players in the Swiss rugby league. METHODS: During the 2010/11 season, 517 rugby players from 19 clubs were questioned about dental trauma as well as the use of mouthguards and other forms of body protection. The level of awareness about tooth avulsion and replantation was also assessed. Participants included athletes from four different leagues; National (155), Premier (122), Women's (90) and Juniors (150). RESULTS: Of the 517 players taking part in the survey, 54.4% had sustained at least one serious injury and 39.5% had sustained a facial injury. One hundred and thirty-nine athletes (37.3%) had observed another player sustain a dental injury during a game, whilst 35 (6.8%) had personally sustained one or more dental injuries. Dental injury rate was considerably higher amongst forwards than backs. Four hundred and fifty-six players (88.2%) wore a mouthguard of which three quarters were tailor-made. Three hundred and thirteen players (60.5%) were aware that an avulsed tooth can be replanted; however, only 27 (5.2%) had heard of the tooth rescue boxes. These results demonstrate that, whilst general injuries occur with regularity in rugby, dental injuries are not amongst the most common forms. This is almost certainly attributable to the high level of mouthguard usage. Particularly for players in the junior league, in which the use of mouthguards was lowest, the risk of dental injury may be reduced by an increased level of education about tooth protection. CONCLUSIONS: To this end, an increased awareness about and usage of tooth rescue boxes would be desirable. It would seem sensible to make the wearing of mouthguards compulsory in contact sports such as rugby. PMID- 22300190 TI - Ohio Appalachian residents' views on smoke-free laws and cigarette warning labels. AB - INTRODUCTION: Smoke-free laws and the addition of graphic warning labels to cigarette packages represent public health policies that can potentially reduce smoking and smoking-related disease. The attitudes and beliefs relating to these policies were examined among residents of Ohio Appalachia, a mostly rural region with high smoking prevalence among its residents. METHODS: Focus groups were conducted with participants from Ohio Appalachia during the summer of 2007. Groups included healthcare providers (n=37), community leaders (n=31), parents (n=19), and young adult women aged 18-26 years (n=27). RESULTS: Most participants were female (94%), non-Hispanic White (94%), and married (65%). Participants believed that most non-smokers supported Ohio's enforced statewide comprehensive smoke-free law that began in 2007, while some smokers opposed the law due to a perceived infringement of their rights. They also reported that most residents and local businesses were abiding by and enforcing the law. Participants supported the addition of graphic warning labels to cigarette packages in the USA. They believed that such warning labels could help deter adolescents and adult non-smokers from smoking initiation, particularly if the negative aesthetic effects of smoking were emphasized. However, they felt the labels would be less effective among current smokers and older individuals living in their communities. CONCLUSIONS: Participants generally held positive views about both the smoke-free law and the addition of graphic warning labels to cigarette packages in the USA. These tobacco-related public health policies are promising strategies for potentially reducing smoking and its associated diseases among residents living in Appalachia. Additional research is needed to further examine support for these policies among more diverse Appalachian populations. PMID- 22300192 TI - A clinical trial of curative surgery under local anesthesia for early breast cancer. PMID- 22300193 TI - Perspectives of allergists/immunologists on the 2009-2010 H1N1 vaccination effort. AB - BACKGROUND: Persons with high-risk conditions such as asthma were a target group for national H1N1 vaccine recommendations. Allergists/immunologists (allergists) are a provider group that could vaccinate persons with asthma and other high-risk conditions. Their level of participation in and experiences with the 2009-2010 H1N1 vaccination campaign are unknown. OBJECTIVE: To describe the experiences of allergists related to the 2009-2010 H1N1 vaccination campaign. METHODS: A cross sectional, mailed survey of a national sample of 1955 allergists providing outpatient care was conducted in June-September 2010. RESULTS: The overall response rate was 72%. Most allergists "strongly recommended" H1N1 vaccine for children, and most "recommended" or "strongly recommended" vaccine for adults. The majority (71%) agreed to participate in the H1N1 vaccine campaign and received vaccine. Vaccine supply was a significant challenge, but otherwise few major problems were experienced with administering H1N1 vaccine. The majority of respondents, particularly among those who participated in the 2009-2010 H1N1 vaccination campaign, felt they would be very likely to vaccinate in the event of future influenza pandemic. CONCLUSIONS: The experiences of allergists in the H1N1 vaccine campaign were generally positive. Most allergists are willing to serve as vaccinators in future influenza pandemics, which will help facilitate broad access to vaccine for patients with asthma and other high-risk conditions. PMID- 22300194 TI - Dynamic internal cavities of dendrimers as constrained media. A study of photochemical isomerizations of stilbene and azobenzene using poly(alkyl aryl ether) dendrimers. AB - Dendritic microenvironments defined by dynamic internal cavities of a dendrimer were probed through geometric isomerization of stilbene and azobenzene. A third generation poly(alkyl aryl ether) dendrimer with hydrophilic exterior and hydrophobic interior was used as a reaction cavity in aqueous medium. The dynamic inner cavity sizes were varied by utilizing alkyl linkers that connect the branch junctures from ethyl to n-pentyl moiety (C(2)G3-C(5)G3). Dendrimers constituted with n-pentyl linker were found to afford higher solubilities of stilbene and azobenzene. Direct irradiation of trans-stilbene showed that C(5)G3 and C(4)G3 dendrimers afforded considerable phenanthrene formation, in addition to cis stilbene, whereas C(3)G3 and C(2)G3 gave only cis-stilbene. An electron-transfer sensitized trans-cis isomerization, using cresyl violet perchlorate as the sensitizer, also led to similar results. Thermal isomerization of cis-azobenzene to trans-azobenzene within dendritic microenvironments revealed that the activation energy of the cis- to trans-isomer was increasing in the series C(5)G3 < C(4)G3 2 mg/L for colistin suggested by European Committee on Antimicrobial Susceptibility Testing (EUCAST) is placed inside the distribution for both Salmonella Dublin and Salmonella Enteritidis. All tested Salmonella Dublin isolates, regardless of MIC colistin value, had identical pmrA and pmrB sequences. Missense mutations were found only in pmrA in one Salmonella Reading and in pmrB in one Salmonella Concord isolate, both with MIC of <=1 for colistin. In conclusion, our study indicates that missense mutations are not necessarily involved in increased MICs for colistin. Increased MICs for colistin seemed to be linked to specific serotypes (Salmonella Dublin and Salmonella Enteritidis). We recommend that Salmonella with MIC of >2 mg/L for colistin be evaluated on the serovar level. PMID- 22300223 TI - Dynamics of Salmonella serotype shifts in an endemically infected dairy herd. AB - Salmonella is a leading cause of foodborne illness in the United States. It is a zoonotic pathogen found in many species of food animals, and contamination of foodstuffs by strains of Salmonella found on farms is an important source of human exposure. Here we describe a long-term (2004-2010) study of Salmonella colonization on a typical dairy farm in the Northeastern United States. The fecal shedding prevalence in the herd ranged from 8% to 97%, and greater than 50% of the herd was shedding Salmonella for more than two-thirds of the study period. Salmonella enterica serotype Cerro was first detected in September 2004, after a small and very short-lived outbreak of Salmonella Kentucky. Cerro persisted within the herd for over 3 years, with no clinical signs of salmonellosis in the animals. In the winter of 2006, Kentucky was again detected within the herd, and over a 2-year period, Kentucky gradually supplanted Cerro. Kentucky was the only serotype detected from March 2008 until September 2009, when Cerro was again detected in 15% of the cows on the farm. Since September 2009, Kentucky and Cerro have coexisted within the herd, which continues to harbor these serotypes at high prevalence. Pulsed-field gel electrophoresis (PFGE) could not discern differences between Cerro strains isolated during this study, but it did suggest that the strain of Kentucky that seemed to behave as a commensal in these dairy cows is distinct from the transient strain isolated in 2004. Understanding the dynamics of competition between these two serotypes that seem to behave as commensal colonizers of dairy cows may provide insights into the mechanisms by which Salmonella establishes infection in the lower gut of dairy cows and may lead to the development of measures to prevent or limit Salmonella colonization of dairy cows. PMID- 22300224 TI - The cytotoxic effect of essential oils from Origanum vulgare L. and/or Rosmarinus officinalis L. on Aeromonas hydrophila. AB - This study aimed to evaluate the antibacterial activities of the essential oils from Origanum vulgare L. (OV) and Rosmarinus officinalis L. (RO), both singly and in combination at sub-inhibitory concentrations (1/4 MIC + 1/4 MIC), against Aeromonas hydrophila and to investigate the possible mechanisms underlying these activities. Used singly (OV: 2.5 MUL/mL; RO: 20 MUL/mL) or in a mixture (OV: 0.625 MUL/mL + RO: 5 MUL/L), these essential oils led to a significant decrease (p<0.01) in bacterial viability after 24 h of exposure. A decrease in glucose consumption by A. hydrophila and release of cellular material were observed immediately after the addition of the essential oils, both singly and as a mixture, and continued for up to 6 h. Electron microscopy of cells exposed to the essential oils revealed severe changes in the plasma membrane, cytoplasmic appearance, and cell shape during the 6-h exposure period. OV and RO essential oils combined at sub-inhibitory concentrations could be rationally applied to inhibit the growth of A. hydrophila in food products, particularly minimally processed vegetables. PMID- 22300225 TI - Seroprevalence and risk factors for brucellosis in a high-risk group of individuals in Bangladesh. AB - Brucellosis is an occupational hazard of livestock farmers, dairy workers, veterinarians, slaughterhouse workers, and laboratory personnel, all of whom are considered to belong to the high-risk occupational group (HROG). A study was undertaken to determine the seroprevalence of brucellosis, identify risk factors associated with brucellosis seropositivity, and detect Brucella at genus level using real-time polymerase chain reaction (PCR) among people in the HROG in the Dhaka division of Bangladesh. A sample of 500 individuals from the HROG was collected from three districts of Dhaka division of Bangladesh. A multiple random effects logistic regression model was used to identify potential risk factors. Two types of real-time PCR methods were applied to detect Brucella genus-specific DNA using serum from seropositive patients. The prevalence of brucellosis based on the three tests was observed to be 4.4% based on a parallel interpretation. The results of the multiple random effects logistic regression analysis with random intercept for district revealed that the odds of brucellosis seropositivity among individuals who had been in contact with livestock for more than 26 years was about 14 times higher as compared to those who had less than 5 years of contact with livestock. In addition, when the contact was with goats, the odds of brucellosis seropositivity were about 60 times higher as compared to when contact was with cattle only. Noticeable variation in brucellosis seropositivity among humans within the three districts was noted. All of the 13 individuals who tested positive for the serological tests were also positive in two types of real-time PCR using the same serum samples. Livestock farmers of brucellosis positive herds had a significantly higher probability to be seropositive for brucellosis. The study emphasized that contact with livestock, especially goats, is a significant risk factor for the transmission of brucellosis among individuals in the HROG. PMID- 22300226 TI - Neurotuberculosis: an overview. AB - Although pulmonary tuberculosis is the most common form of this disease, neurotuberculosis is more severe and presents higher morbidity and mortality. Its diagnosis continues to challenge physicians all over the world. Contributing to this fact is the nonspecificity of its clinical manifestations, the low density of bacilli in the cerebrospinal fluid (CSF), and the delayed recovery of Mycobacterium tuberculosis through culture techniques. Thus, the diagnosis is largely based on suspicious symptoms, and the prognosis is directly related to the stage of the disease at the beginning of treatment. Even thought there is no consensus regarding the best therapeutic regimen, the WHO recommends using the same regimen used for pulmonary tuberculosis with a longer treatment time. It is important to note that in most cases, the doctor will not have a definite diagnosis at the beginning of the treatment. However, this should not delay the initiation of therapy. A delay in initiating treatment, in most cases, is directly associated with a poor prognosis. This review gives an overview of the current state of the neurotuberculosis research. It covers the epidemiological aspects of the infection, pathogenesis, principal clinical presentations, diagnosis highlighting neuroimaging, where a series of imaging are presented, prognosis, prevention and therapeutic regimens. PMID- 22300227 TI - HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP): still an obscure disease. AB - Human T-cell leukemia virus type 1 (HTLV-1) is the ethiologic agent of the neurological disorder HTLV-1- associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the majority of HTLV-1-infected individuals remain asymptomatic during their lifetime, approximately one percent of this population develops a myelopathy consisting of a chronic inflammation of the white and gray matter of the spinal cord. Glucocorticoids are widely used for treatment because of their anti-inflammatory properties, improving symptoms mainly in those patients with only a few years from onset of the disease, when inflammation is more prominent. Interferon-alpha and vitamin C are other therapies presenting some benefits in clinical practice, probably due to their anti-viral and immunomodulatory activities observed ex vivo. Furthermore, inhibitors of histone deacetylase, which increase virus expression but result in a substantial decline in the proviral load, have also been proposed. This review is intended to bridge the gap between clinical and basic science by presenting recent findings on HAM/TSP disease, mechanisms of drug action, and benefits of these therapies in HAM/TSP patients. PMID- 22300228 TI - Neurocysticercosis: the enigmatic disease. AB - Neurocysticercosis (NCC) is an infection of the central nervous system (CNS) caused by the metacestode larval form of the parasite Taenia sp. Many factors can contribute to the endemic nature of cysticercosis. The inflammatory process that occurs in the tissue surrounding the parasite and/or distal from it can result from several associated mechanisms and may be disproportionate with the number of cysts. This discrepancy may lead to difficulty with the proper diagnosis in people from low endemic regions or regions that lack laboratory resources. In the CNS, the cysticerci have two basic forms, isolated cysts (Cysticercus cellulosae=CC) and racemose cysts (Cysticercus racemosus=CR), and may be meningeal, parenchymal, or ventricular or have a mixed location. The clinical manifestations are based on two fundamental syndromes that may occur in isolation or be associated: epilepsy and intracranial hypertension. They may be asymptomatic, symptomatic or fatal; have an acute, sub-acute or chronic picture; or may be in remission or exacerbated. The cerebrospinal fluid (CSF) may be normal, even in patients with viable cysticerci, until the patients begin to exhibit the classical syndrome of NCC in the CSF, or show changes in one or more routine analysed parameters. Computed tomography (CT) and magnetic resonance imaging (MRI) have allowed non-invasive diagnoses, but can lead to false negatives. Treatment is a highly controversial issue and is characterised by individualised therapy sessions. Two drugs are commonly used, praziquantel (PZQ) and albendazole (ABZ). The choice of anti-inflammatory drugs includes steroids and dextrochlorpheniramine (DCP). Hydrocephalus is a common secondary effect of NCC. Surgical cases of hydrocephalus must be submitted to ventricle-peritoneal shunt (VPS) immediately before cysticidal treatment, and surgical extirpation of the cyst may lead to an absence of the surrounding inflammatory process. The progression of NCC may be simple or complicated, have remission with or without treatment and may exhibit symptoms that can disappear for long periods of time or persist until death. Unknown, neglected and controversial aspects of NCC, such as the impaired fourth ventricle syndrome, the presence of chronic brain oedema and psychic complaints, in addition to the lack of detectable glucose in the CSF and re-infection are discussed. PMID- 22300229 TI - Improving cognitive outcome in cerebral malaria: insights from clinical and experimental research. AB - Cerebral Malaria (CM) is a clinical syndrome defined by the World Health Organization (WHO) as a potentially reversible diffuse encephalopathy characterized mainly by coma and the presence of asexual forms of Plasmodium falciparum parasites in peripheral blood smears in the absence of other causes of encephalopathy. A wide range of clinical manifestations follows the disease including cognitive, behavioral and motor dysfunctions, seizures and coma. The underlying mechanisms of CM pathogenesis remain incompletely understood although vascular, immunological and metabolic changes have been described. The classical treatment of CM is based on the administration of antimalarial drugs, especially chloroquine and artemisinin derivates as artesunate. Even with treatment, 15 to 20% of children with CM die and approximately 10 to 17% of those who survive remain with significant long-term cognitive impairment. In this context, neuroprotective and adjuvant therapies have been recently investigated in clinical and experimental studies of CM in an attempt to improve cognitive outcome. A poor understanding of pathophysiological mechanisms, properties of compounds used and patient selection have contributed to the lack of success of these interventions. This review discusses clinical aspects of cognitive sequelae, possible mechanisms involved in the brain injury, perspectives and limitations regarding the pharmacological strategies to improve cognitive outcome in CM. PMID- 22300230 TI - Arboviral encephalitis and RNAi treatment. AB - Encephalitis refers to an acute, usually diffuse, inflammatory process affecting the brain. The clinical hallmark of acute encephalitis is the triad of fever, headache, and altered mental status. The most common and important cause of encephalitis is the infection by a virus although other organisms can cause the disease. This article is a general overview of the most common viral encephalitides, divided into two families, Flavivirus and Alphavirus, and provides details about virus and RNA interference. More detailed descriptions of each viral family are provided below. PMID- 22300231 TI - Symptoms in euthyroid Hashimoto's thyroiditis: is there a role for autoimmunity itself? PMID- 22300232 TI - Perception of earthquake risk in Taiwan: effects of gender and past earthquake experience. AB - This study explored how individuals in Taiwan perceive the risk of earthquake and the relationship of past earthquake experience and gender to risk perception. Participants (n= 1,405), including earthquake survivors and those in the general population without prior direct earthquake exposure, were selected and interviewed through a computer-assisted telephone interviewing procedure using a random sampling and stratification method covering all 24 regions of Taiwan. A factor analysis of the interview data yielded a two-factor structure of risk perception in regard to earthquake. The first factor, "personal impact," encompassed perception of threat and fear related to earthquakes. The second factor, "controllability," encompassed a sense of efficacy of self-protection in regard to earthquakes. The findings indicated prior earthquake survivors and females reported higher scores on the personal impact factor than males and those with no prior direct earthquake experience, although there were no group differences on the controllability factor. The findings support that risk perception has multiple components, and suggest that past experience (survivor status) and gender (female) affect the perception of risk. Exploration of potential contributions of other demographic factors such as age, education, and marital status to personal impact, especially for females and survivors, is discussed. Future research on and intervention program with regard to risk perception are suggested accordingly. PMID- 22300233 TI - Regional quantification of muscarinic acetylcholine receptors and beta adrenoceptors in human airways. AB - BACKGROUND AND PURPOSE Muscarinic acetylcholine receptors (mAChRs) and beta adrenoceptors in the airways and lungs are clinically important in chronic obstructive pulmonary disease (COPD) and asthma. However, the quantitative and qualitative estimation of these receptors by radioligand binding approaches in human airways has not yet been reported because of tissue limitations. EXPERIMENTAL APPROACH The regional distribution and relative proportion of mAChR and beta-adrenoceptor subtypes were evaluated in human bronchus and lung parenchyma by a tissue segment binding method with [(3)H]-N-methylscopolamine ([(3)H]-NMS) for mAChRs and [(3)H]-CGP-12,177 for beta-adrenoceptors. Functional responses to carbachol and isoprenaline were also analysed in the bronchus. KEY RESULTS The M(3) subtype predominantly occurred in the bronchus, but the density decreased from the segmental to subsegmental bronchus, and was absent in lung parenchyma. On the other hand, the M(1) subtype occurred in the lung only, and the M(2) subtype was distributed ubiquitously in the bronchus and lungs. beta(2) adrenoceptors were increased along the airways, and their densities in the subsegmental bronchus and lung parenchyma were approximately twofold higher than those of mAChRs in the same region. beta(1)-adrenoceptors were also detected in lung parenchyma but not in the bronchus. The muscarinic contractions and adrenoceptor relaxations in both bronchial regions were mediated through M(3) mAChRs and beta(2)-adrenoceptors, respectively. CONCLUSIONS AND IMPLICATIONS From the present radioligand binding approach with intact tissue segments, we constructed a distribution map of mAChRs and beta-adrenoceptors in human bronchus and lung parenchyma for the first time, providing important evidence for future pharmacotherapy and new drug development for respiratory disorders. PMID- 22300234 TI - Lipid droplet de novo formation and fission are linked to the cell cycle in fission yeast. AB - Cells sequester neutral lipids in bodies called lipid droplets. Thus, the formation and breakdown of the droplets are important for cellular metabolism; unfortunately, these processes are difficult to quantify. Here, we used time lapse confocal microscopy to track the formation, movement and size changes of lipid droplets throughout the cell cycle in fission yeast Schizosaccharomyces pombe. In theory, the number of lipid droplets in these cells must increase for daughter cells to have the same number of droplets as the parent at a reference point in the cell cycle. We observed stable droplet formation events in G2 phase that were divided evenly between de novo formation of nascent droplets and fission of preexisting droplets. The observations that lipid droplet number is linked to the cell cycle and that droplets can form via fission were both new discoveries. Thus, we scrutinized each fission event for multiple signatures to eliminate possible artifacts from our microscopy. We augmented our time-lapse confocal microscopy with electron microscopy, which showed lipid droplet 'intermediates': droplets shaped like dumbbells that are potentially in transition states between two spherical droplets. Using these complementary microscopy techniques and also dynamic simulations, we show that lipid droplets can form by fission. PMID- 22300237 TI - Ber-EP4 is a useful marker for follicular germinative cell differentiation of cutaneous epithelial neoplasms. AB - Ber-EP4 is a monoclonal antibody that recognizes 34-kDa and 39-kDa non-covalently linked glycopolypeptides expressed by most human epithelial cells and carcinomas. In this study, we performed immunohistochemical staining of 31 cases of basal cell carcinoma (BCC); 20 cases of trichoblastoma (TB), including ten cases of nodular type, eight cases of cribriform type (trichoepithelioma) and two cases of columnar type (desmoplastic trichoepithelioma); 16 cases of actinic keratosis (AK); and 10 cases each of Bowen's disease, poroma and seborrheic keratosis. Six cases of BCC and AK were co-lesions of both neoplasms. In normal skin tissue, Ber EP4 reacted positively with the secretory portion of eccrine glands and follicular germinative cells at the lower end of catagen hairs. Neoplastic cells in 97% of cases with BCC reacted positively with Ber-EP4 in at least 5% of neoplastic cells. Those in 90% with nodular type TB and 50% with trichoepithelioma also reacted positively in at least 5% of neoplastic cells. No cases of poroma, seborrheic keratosis, AK or Bowen's disease were immunohistochemically positive for Ber-EP4 in neoplastic cells. In all six cases with co-lesions of BCC and AK, neoplastic cells of BCC reacted positively with Ber-EP4 and those of AK were negative. Immunohistochemical examination using the Ber-EP4 antibody is a useful tool for diagnosing neoplasms with follicular germinative differentiation, such as TB, TE or BCC, and for differentiating those from squamous cell carcinoma in situ, poroma or seborrheic keratosis. PMID- 22300239 TI - Absolute free energy of binding of avidin/biotin, revisited. AB - The binding of biotin to avidin is one of the strongest in nature with absolute free energy of binding, DeltaA(0) = -20.4 kcal/mol. Therefore, this complex became a target for a large number of computational studies, which all, however, are based on approximate techniques or simplified models and have led to a wide range of results Therefore, DeltaA(0) is calculated here by rigorous statistical mechanical methods and models that consider long-range electrostatics. (1) We apply our method, "hypothetical scanning molecular dynamics with thermodynamic integration" (HSMD-TI) to avidin-biotin modeled by periodic boundary conditions with particle mesh ewald (PME). (2) We apply the double decoupling method (DDM) to this system modeled by the spherical solvent boundary potential (SSBP) and the generalized solvent boundary potential (GSBP). The corresponding results for neutral biotin, DeltaA(0) = -29.1 +/- 0.8 and -25.2 +/- 0.5 kcal/mol are significantly lower than the experimental value; we also provide the result for a charged biotin, DeltaA(0) = -33.3 +/- 0.8 kcal/mol. It is plausible to suggest that this disagreement with the experiment may stem from ignoring the (positive) contribution of a mobile loop that changes its structure upon ligand binding. PMID- 22300240 TI - Children of parents with intellectual disability: facing poor outcomes or faring okay? AB - BACKGROUND: Children of parents with intellectual disability are assumed to be at risk of poor outcomes but a comprehensive review of the literature has not previously been undertaken. METHOD: A database and reference search from March 2010 to March 2011 resulted in 26 studies for review. RESULTS: Two groups of studies were identified. The first investigated an association between parental intellectual disability and child outcomes where there was significant disadvantage. Some findings suggest low parental intellectual capacity can negatively impact child outcomes, but others indicate child development approaches population norms. A second, small group of studies explored narrative accounts of childhood to find that social exclusion, bullying, and stigma are commonplace. Removal from parental care emerged as a significant risk for this group of children. CONCLUSIONS: Studies focusing on child development represent 85% of the literature but reach no consensus about likely developmental or behavioural outcomes. Children studied usually come from clinical populations or other high-risk groups, and are typically young children. PMID- 22300241 TI - Depressive symptoms and level of physical activity in patients with Alzheimer's disease. AB - AIM: The purpose of this study was to determine the presence of depressive symptoms in patients with Alzheimer's disease, to assess whether there was an association between physical activity level and depressive symptoms in this population, and to assess whether more active patients had lower rates of depressive symptoms when compared with less active patients. METHODS: The study included 37 patients with Alzheimer's disease and used the following instruments: the Geriatric Depression Scale, the Cornell Scale for Depression in Dementia and the Baecke Questionnaire Modified for the Elderly. The Shapiro-Wilk test was used to determine whether the data were normally distributed. The Spearman correlation test and the Mann-Whitney U-test was used. P-values less than 5% were considered statistically significant. RESULTS AND DISCUSSION: The prevalence of depressive symptoms in the sample was 35.13%. The Spearman correlation test verified the relationship between level of physical activity and depressive symptoms (rho = 0,4), and between the sports activities domain and depressive symptoms (rho = 0,4). Patients who were more active had lower depressive symptoms. CONCLUSIONS: The prevalence of depressive symptoms in the sample was 35.13%. Patients who were more active had lower rates of depressive symptoms. PMID- 22300243 TI - Depletion of leaf-type ferredoxin-NADP(+) oxidoreductase results in the permanent induction of photoprotective mechanisms in Arabidopsis chloroplasts. AB - Arabidopsis thaliana contains two photosynthetically competent chloroplast targeted ferredoxin-NADP(+) oxidoreductase (FNR) isoforms that are largely redundant in their function. Nevertheless, the FNR isoforms also display distinct molecular phenotypes, as only the FNR1 is able to directly bind to the thylakoid membrane. We report the consequences of depletion of FNR in the F(1) (fnr1 * fnr2) and F(2) (fnr1 fnr2) generation plants of the fnr1 and fnr2 single mutant crossings. The fnr1 * fnr2 plants, with a decreased total content of FNR, showed a small and pale green phenotype, accompanied with a marked downregulation of photosynthetic pigment-protein complexes. Specifically, when compared with the wild type (WT), the quantum yield of photosystem II (PSII) electron transport was lower, non-photochemical quenching (NPQ) was higher and the rate of P700(+) re reduction was faster in the mutant plants. The slight over-reduction of the plastoquinone pool detected in the mutants resulted in the adjustment of the reactive oxygen species (ROS) scavenging systems, as both the content and de epoxidation state of xanthophylls, as well as the content of alpha-tocopherol, were higher in the leaves of the mutant plants when compared with the WT. The fnr1 fnr2 double mutant plants, which had no detectable FNR and possessed an extremely downregulated photosynthetic machinery, survived only when grown heterotrophically in the presence of sucrose. Intriguingly, the fnr1 fnr2 plants were still capable of sustaining the biogenesis of a few malformed chloroplasts. PMID- 22300246 TI - Environmental asbestos exposure in rural Turkey and risk of lung cancer. AB - The aim of this study was to determine the risk of lung cancer in a cohort of villagers with environmental asbestos exposure. The study was carried out as a field-based epidemiological study. Information from 3143 individuals in 15 asbestos exposed villages and 2175 individuals in 12 control villages was obtained. Asbestos fiber type to which villagers were exposed mainly was tremolite or tremolite, actinolite, chrysotile mixtures. The cumulative fiber count of the villagers during their lifespan ranged from 0.19 to 4.61 fiber years/ml. The annual average incidence ratio of lung cancer was 135.21/100,000 persons/year in men and 47.28 in women in the asbestos exposed villages. For the control villages, this ratio was 60.15/100,000 person/year in men and 15.06 in women. Being a male, advanced age, smoking and asbestos exposure were established to increase the risk of lung cancer. Environmental asbestos exposure in rural area is a risk factor for lung cancer independent of smoking. PMID- 22300247 TI - Amicrobial pustulosis associated with autoimmune disease in a patient with Sjogren syndrome and IgA nephropathy. AB - Amicrobial pustulosis associated with autoimmune disease (APAD) is a rare clinical condition, characterized by relapsing pustular eruption, affecting mainly the skin folds. Almost all previously described cases were young women with varying underlying autoimmune diseases. We report a 36-year-old woman with the interesting triad of APAD, Sjogren syndrome and IgA nephropathy. Her rashes responded to oral prednisolone and cyclophosphamide. PMID- 22300248 TI - Reliability and validity of the Norwegian child and parent versions of the DISABKIDS Chronic Generic Module (DCGM-37) and Diabetes-Specific Module (DSM-10). AB - BACKGROUND: International guidelines on type 1 diabetes advocate routine screening of health-related quality of life (HRQOL). DISABKIDS questionnaires are the first instruments developed across cultures and nations to provide age appropriate measures of HRQOL in children with chronic diseases. DISABKIDS includes a Chronic Generic Module 37 (DCGM-37) and disease-specific modules. The purpose of this study was to examine reliability and validity of the Norwegian versions of the DISABKIDS questionnaires in children and adolescents with type 1 diabetes. METHODS: The DCGM-37 and the Diabetes Specific Module-10 (DDM-10) were translated into Norwegian using standard forward-backward translation. Eight to 19 year old children and adolescents with type 1 diabetes scheduled for routine follow-up at three diabetic clinics in Norway and one of their parents were invited to complete the DCGM-37 and the DDM-10. Internal consistency was determined using Cronbach's alpha. Results were compared with those of the Child Health Questionnaire Children Form-87 (CHQ-CF87) and Child Health Questionnaire Parent Form-50 which are established generic questionnaires. DISABKIDS results were related to age, gender, duration of diabetes, mode of insulin delivery and metabolic control. Clinical data were obtained from the Norwegian Childhood Diabetes Registry. RESULTS: Of 198 eligible child-parent dyads, 103 (52%) completed the questionnaires. Mean age was 13.6 (2.6), range 8-19 yrs, 52% were boys. Cronbach's alpha was > 0.70 for all the DISABKIDS sub-scales except two (physical ability and social inclusion). There were moderate to high correlations (0.65-0.81) between the DISABKIDS scales and mental/emotional sub-scales of CHQ CF87. Increasing age and higher HbA1c were significantly associated with reduced HRQOL scores. Parents tended to score their child's HRQOL lower than the children/adolescents themselves. CONCLUSIONS: The study shows that the DISABKIDS instruments are applicable to a Norwegian childhood diabetes population. They seem to be a relevant supplement to other clinical indicators in medical practice and research. PMID- 22300249 TI - Papillary thyroid carcinoma arising from a primary thyroglossal duct cyst with cervical node metastases. PMID- 22300250 TI - Histopathological diagnoses of "accessory" thyroid nodules diagnosed as benign by fine-needle aspiration cytology and ultrasonography. AB - BACKGROUND: Patients who have thyroidectomies for thyroid nodules that are suspected of being malignant, called here "main nodules," occasionally have second nodules, called here "accessory nodules" that are evaluated by ultrasonography (US) and fine-needle aspiration cytology (FNAC). Most accessory nodules are diagnosed as benign based on preoperative US and FNAC. To evaluate the accuracy of US and FNAC for a group of nodules which were likely to be mostly benign we evaluated procedures to diagnose accessory nodules. PATIENTS AND METHODS: In a total of 643 patients who underwent thyroidectomy for their main nodules, 866 accessory nodules were evaluated by US and/or FNAC preoperatively. All were evaluated by histopathological examination postoperatively. Of the 866 accessory nodules, 501 were evaluated by US only and 365 were evaluated by US and FNAC. RESULTS: While the 363 accessory nodules were diagnosed as malignant by histopathology, 235 nodules were malignant by US and histopathology and 115 nodules were malignant by FNAC and histopathology. Among the accessory nodules that were diagnosed as benign by histopathology, 7.2% were malignant by US, and 4.4% were malignant by FNAC. Among the accessory nodules that were diagnosed as benign by FNAC, 15.0% were malignant by histopathology. This was a significantly higher percentage than the value of 6.2% for the accessory nodules diagnosed as benign by US but malignant by histopathology. Accessory nodules with a benign cytology on FNAC that were malignant were significantly smaller than those with a benign cytology and histopathology. Among the 126 accessory nodules that were read as benign by both US and FNAC, only one (0.8%) was diagnosed as papillary thyroid carcinoma by histopathology. CONCLUSION: These data suggest that diagnostic accuracy of benign nodules based on both US and cytological evaluation was supported by the evidence of high-level histopathological compatibility in accessory nodules. FNAC and US have a low but not negligible false-negative diagnostic rate. When FNAC is combined with US the false-negative rate is probably very low. PMID- 22300251 TI - The utility of I-123 pretherapy scan in I-131 radioiodine therapy for thyroid cancer. AB - BACKGROUND: There is a growing belief that a pretherapy scan yields little or no additional information that would impact on radioiodine ablation dosing. In addition, there is some concern regarding on the stunning effect of a pretherapy scan, especially when I-131 radioisotope is used for imaging. We hypothesized that a pretherapy scan provides invaluable information on the amount of thyroid remnant, sometimes indicating the need for two-step I-131 ablation. It may also detect unsuspected local lymph node involvement or distant metastases, indicating the requirement for a higher I-131 dose after thyroidectomy. The aim of this study was to evaluate how effective pretherapy scans are for guiding I-131 therapy planning and augmenting information provided in the pathology reports for thyroidectomy specimens. METHODS: We reviewed 122 patients who underwent I-123 pretherapy scan and I-131 radioablation at Yale New Haven Hospital between January 2006 and August 2007. The percentage of neck uptake and whole-body images were acquired 24 hours following the administration of 51.8 MBq (1.4 mCi) of I 123 NaI. A 24-hour uptake of >3% was used as the cutoff to determine whether there was a greater than desired quantity of thyroid remnant, which would require a two-step treatment protocol. Furthermore, attention was paid to identifying cervical lymph nodes, which may not have presented themselves in the euthyroid state at the time of thyroidectomy. Additional clinical information provided by pretherapy scans was computed as percentages with 95% confidence intervals by using adjusted Wald intervals. RESULTS: Overall, the pretherapy scans provided additional critical information in 25% of the cases (31/122; 95% CI: 18%-34%). For cases demonstrating >3% uptake with midline lymph nodes, the pretherapy scan provided additional information in 50% of the cases (8/16; 95% CI: 28%-72%). CONCLUSIONS: Our study demonstrated that I-123 pretherapy scans provide valuable information with regard to unsuspected lymph nodes or distant metastases, indicating the requirement for a significantly higher I-131 dose, and unexpected large thyroid remnants, suggesting the need for two-step ablation. We should take advantage of stimulated pretherapy scans and adjust the treatment dosing accordingly. PMID- 22300252 TI - Assembly of 3-substituted isocoumarins via a CuI-catalyzed domino coupling/addition/deacylation process. AB - An efficient strategy for the synthesis of a variety of 3-substituted isocoumarins has been developed. The reaction proceeded from o-halobenzoic acids and 1,3-diketones via a copper(I)-catalyzed domino reaction in DMF under the action of K(3)PO(4) at 90-120 degrees C without a ligand to afford the corresponding 3-substituted isocoumarin derivatives in good to excellent yields. o-Halobenzoic acids could be o-iodobenzoic acid, o-bromobenzoic acid, and o chlorobenzoic acid derivatives. 1,3-Diketones could be alkyl- and aryl substituted 1,3-diketones. PMID- 22300254 TI - Transaxillary subpectoral implantation of implantable pulse generator for deep brain stimulation. AB - OBJECTIVES: Deep brain stimulation (DBS) is an effective modality of treating cardinal motor symptoms of several movement disorders such as Parkinson's disease, essential tremor, and dystonia. Although hardware-related complications of DBS have been reported, the cosmetic satisfaction and discomfort associated with infraclavicular subcutaneous implantation of the pulse generator has not been described. The authors adopted a technique of transaxillary subpectoral implantable pulse generator (IPG) placement and investigated the difference in the discomfort, cosmetic satisfaction, mean operation time for IPG implantation, and severity of postoperative pain between infraclavicular subcutaneous placement and transaxillary subpectoral implantation of IPG. MATERIALS AND METHODS: 25 patients who underwent bilateral, infraclavicular subcutaneous IPG placement for DBS and 15 patients who had bilateral, transaxillary subpectoral IPG placement were investigated. RESULTS: The differences in cosmetic satisfaction and discomfort between the two groups were significant. The cosmetic satisfaction was higher and discomfort was less in the subpectoral IPG implantation group (p = 0.002 and p = 0.000). However, more time was needed for IPG implantation, and the postoperative pain was more severe after subpectoral IPG implantation (p = 0.002 and p = 0.000). There was no difference in cosmetic satisfaction according to sex (p = 0.907). There was one transient intercostobrachial nerve injury in the subpectoral IPG implantation group and two infections which needed removal of one side of the DBS hardware in the infraclavicular IPG implantation group. CONCLUSIONS: These results demonstrated that subpectoral transaxillary IPG implantation can provide better cosmetic satisfaction in patients undergoing DBS, with less discomfort and morbidity related to erosion and infection. PMID- 22300255 TI - Parents matter--but relations to parents do not explain gender differences in self-reported health in adolescents. AB - The aim of the study was to explore whether parent-adolescent relations are associated to self-reported health of adolescents. Logistic regression analyses were performed on a cross-sectional data set consisting of 5060 adolescents, grades 7-9, from six municipalities in the northern part of Sweden. The study was approved by the Regional Ethical Review Board in Umea, Sweden. Results showed that, in both boys and girls, experiencing low parental demands as well as perceiving the relationship quality and the communication with parents as poor were significantly associated with having poor general health, somatic complaints and feelings of stress. In general, girls scored lower on self-reported health than boys, but our findings indicate that these gender differences could not be explained by relations to parents. In conclusion, relations to parents play an important role for self-reported health of adolescents. Although no causal-effect statements can be determined in this study, it is implied that there is a need for health professionals, such as school nurses, school welfare officers, etc., to pay special attention to parent-adolescent relations in their work with adolescents. PMID- 22300256 TI - Galactone-gamma-lactone-dependent ascorbate biosynthesis alters wheat kernel maturation. AB - Kernel development and maturation involve several well-characterised events, such as changes in ascorbate (ASC) metabolism, protein synthesis and storage, programmed cell death (PCD) of starchy endosperm and tissue dehydration. Despite many studies focusing on these events, whether and how they are metabolically related to each other, remains to be elucidated. In the present investigation, the changes in ASC-related metabolism, PCD occurrence, kernel filling and dehydration have been analysed during kernel maturation, over a 3-year period in plants grown under normal conditions and in plants displaying modified ASC synthesis. The obtained results suggest that ASC plays a pivotal role in the network of events characterising kernel maturation. During this process, a decrease in ASC content occurs. When ASC biosynthesis is improved in the kernel, by feeding the plants with its immediate precursor, L-galactone-gamma-lactone (GL), the decrease in ASC, observed during kernel maturation, is delayed. As a consequence, ascorbate peroxidase (APX) activity is also enhanced. Moreover, a delay in the ASC decrease permits a delay in PCD occurring in kernel storage tissues and in kernel dehydration. Interestingly, the data emerging from the present investigation suggest that the delay in the decrease in ASC content and APX activity also improves kernel filling. The relevance of the ascorbate dependent redox regulation for kernel productivity is discussed. PMID- 22300253 TI - Regulation of DNA glycosylases and their role in limiting disease. AB - This review will present a current understanding of mechanisms for the initiation of base excision repair (BER) of oxidatively-induced DNA damage and the biological consequences of deficiencies in these enzymes in mouse model systems and human populations. PMID- 22300257 TI - Patterns of communicative interaction between a child with severe speech and physical impairments and her caregiver during a mealtime activity. AB - BACKGROUND: Interaction between caregivers and children with severe impairments is closely related to the demands of daily activities. This study examines the relationship between interaction and the routine mealtime activity at home. METHOD: Patterns of interaction between a child (aged 6 years and 6 months) with severe speech and physical impairments and her caregiver (focus dyad) and a child without impairments (aged 6 years and 6 months) and her caregiver (comparison dyad) were analysed using video recordings and activity-based communication analysis. RESULTS: The focus dyad's interaction was unaided. The dyad did not use the Blissymbol board but communicated using words, vocalisations, word approximations, and body communication. Interaction in the focus dyad included relatively few pauses and frequent interchanges of short and sometimes simultaneous communicative contributions. Strong relations between patterns of interaction and immediate activity management goals such as assisting with eating, eating and drinking were found and compared for the two dyads. Results were discussed with regard to child development and communication intervention. CONCLUSIONS: The focus dyad showed interactive efficiency and the fulfilment of goals relating to basic understanding and closeness, but mainly with regard to immediate mealtime issues. The comparison child and caregiver were more independent in the activity which made it possible for them to reach more extensive, and from a child perspective, age-adequate goals than the focus dyad. PMID- 22300260 TI - Comparison of pregnancy outcomes in natural cycle IVF/M treatment with or without mature oocytes retrieved at time of egg collection. AB - The objective of this study is to compare the pregnancy and live birth rates of a natural cycle in vitro fertilization (IVF) combined with in vitro maturation (IVM) treatment (natural cycle IVF/M) by the presence or absence of mature oocytes retrieved. Infertile women were divided into two groups: (A) patients with mature oocytes found at retrieval and (B) patients with only immature oocytes at retrieval. Patients of group A were further divided into three subgroups: (A1) mature oocytes retrieved from both the leading and the small follicles, (A2) mature oocytes retrieved from the leading follicles only, and (A3) mature oocytes retrieved from the small follicles only. Pregnancy and implantation rates were compared. The results indicate that the clinical pregnancy rates were 40.1% (126/314) and 34.5% (19/55) for groups A and B, respectively. There were no differences in pregnancy rates among the subgroups: A1=44.0% (66/150), A2=34.9% (30/86), and A3=38.5% (30/78). In addition there were no differences in implantation rates among the groups (16.2% =139/859, 15.0% =22/147, 16.8% =69/410, 14.7% =34/232, and 16.6% =36/217, respectively). However, the live birth and miscarriage rates were significantly different between the group A and group B (29.6% =93/314 vs. 16.4% =9/55 and 26.2% =32/126 vs. 52.6% =10/19, respectively). In conclusion, for natural cycle IVF/M treatment, although the clinical pregnancy rates are not different regarding the retrieval of mature oocytes or the time of the egg retrieval, the live birth rate is higher (P < 0.05) when the mature oocytes are obtained at the time of the egg retrieval. PMID- 22300258 TI - Non-systemic drugs: a critical review. AB - Non-systemic drugs act within the intestinal lumen without reaching the systemic circulation. The first generation included polymeric resins that sequester phosphate ions, potassium ions, or bile acids for the treatment of electrolyte imbalances or hypercholesteremia. The field has evolved towards non-absorbable small molecules or peptides targeting luminal enzymes or transporters for the treatment of mineral metabolism disorders, diabetes, gastrointestinal (GI) disorders, and enteric infections. From a drug design and development perspective, non-systemic agents offer novel opportunities to address unmet medical needs while minimizing toxicity risks, but also present new challenges, including developing a better understanding and control of non-transcellular leakage pathways into the systemic circulation. The pharmacokinetic pharmacodynamic relationship of drugs acting in the GI tract can be complex due to the variability of intestinal transit, interaction with chyme, and the complex environment of the surface epithelia. We review the main classes of nonabsorbable agents at various stages of development, and their therapeutic potential and limitations. The rapid progress in the identification of intestinal receptors and transporters, their functional characterization and role in metabolic and inflammatory disorders, will undoubtedly renew interest in the development of novel, safe, non-systemic therapeutics. PMID- 22300262 TI - The omega-3 polyunsaturated fatty acid eicosapentaenoic acid inhibits mouse MC-26 colorectal cancer cell liver metastasis via inhibition of PGE2-dependent cell motility. AB - BACKGROUND AND PURPOSE: The omega-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA) has antineoplastic activity at early stages of colorectal carcinogenesis, relevant to chemoprevention of colorectal cancer (CRC). We tested the hypothesis that EPA also has anti-CRC activity at later stages of colorectal carcinogenesis, relevant to treatment of metastatic CRC, via modulation of E-type PG synthesis. EXPERIMENTAL APPROACH: A BALB/c mouse model, in which intrasplenic injection of syngeneic MC-26 mouse CRC cells leads to development of liver metastases, was used. Dietary EPA was administered in the free fatty acid (FFA) form for 2 weeks before and after ultrasound-guided intrasplenic injection of 1 * 10(6) MC-26 cells (n= 16 each group). KEY RESULTS: Treatment with 5% (w w(-1)) EPA-FFA was associated with a reduced MC-26 mouse CRC cell liver tumour burden compared with control animals (median liver weight 1.03 g vs. 1.62 g; P < 0.034). Administration of 5% EPA-FFA was also linked to a significant increase in tumour EPA incorporation and lower intratumoural PGE(2) levels (with concomitant increased production of PGE(3)). Liver tumours from 5% EPA-FFA- treated mice demonstrated decreased 5-bromo-2-deoxyuridine-positive CRC cell proliferation and reduced phosphorylated ERK 1/2 expression at the invasive edge of tumours. A concentration-dependent reduction in MC-26 CRC cell Transwell(r) migration following EPA-FFA treatment (50-200 uM) in vitro was rescued by exogenous PGE(2) (10 uM) and PGE(1)-alcohol (1 uM). CONCLUSIONS AND IMPLICATIONS: EPA-FFA inhibits MC-26 CRC cell liver metastasis. EPA incorporation is associated with a 'PGE(2) to PGE(3) switch' in liver tumours. Inhibition of PGE(2)-EP(4) receptor-dependent CRC cell motility probably contributes to the antineoplastic activity of EPA. PMID- 22300263 TI - A new multiscale algorithm and its application to coarse-grained peptide models for self-assembly. AB - Peptide self-assembly plays a role in a number of diseases, in pharmaceutical degradation, and in emerging biomaterials. Here, we aim to develop an accurate molecular-scale picture of this process using a multiscale computational approach. Recently, Shell (Shell, M. S. J. Chem. Phys. 2008, 129, 144108-7) developed a coarse-graining methodology that is based on a thermodynamic quantity called the relative entropy, a measure of how different two molecular ensembles behave. By minimizing the relative entropy between a coarse-grained peptide system and a reference all-atom system, with respect to the coarse-grained model's force field parameters, an optimized coarse-grained model can be obtained. We have reformulated this methodology using a trajectory-reweighting and perturbation strategy that enables complex coarse-grained models with at least hundreds of parameters to be optimized efficiently. This new algorithm allows for complex peptide systems to be coarse-grained into much simpler models that nonetheless recapitulate many correct features of detailed all-atom ones. In particular, we present results for a polyalanine case study, with attention to both individual peptide folding and large-scale fibril assembly. PMID- 22300264 TI - Incontinentia pigmenti with NEMO mutation in a Japanese family. PMID- 22300265 TI - A survey of gastrointestinal parasites of olive baboons (Papio anubis) in human settlement areas of Mole National Park, Ghana. AB - Fecal samples from 55 free-ranging olive baboons (Papio anubis) in Mole National Park, Ghana, were collected 22 June-7 July 2008 and analyzed for gastrointestinal parasites. This is the first survey of baboon gastrointestinal parasites in Ghana and provides baseline data for this area. Ninety-three percent of samples were infected, leaving 7% with no parasites observed. Of those infected, there was a 76% prevalence of strongyles, 53% Strongyloides spp., 11% Abbreviata caucasica , 62% prevalence of Balantidium coli (trophozoites and cysts identified), 4% Entomeba hystolytica/dispar, and 47% unidentified protozoan parasites. Of the strongyle infections, 9% were identified as Oesophagostamum sp. One sample contained an unidentified spirurid nematode that resembled Gongylonema sp. Mole has a mixed forest-savanna habitat, and baboons frequently range into human areas, which makes them subject to parasites from each habitat and multiple sources of exposure. We found a high prevalence of nematode parasites, consistent with a wet or cooler forest environment, or high rates of fecal contamination. The presence of Strongyloides sp., E. hystolitica/dispar, and B. coli suggest potential public health risk from baboons, but molecular identification of these parasites, and documentation of their presence in local human populations, would be necessary to confirm zoonotic transmission. PMID- 22300266 TI - A national survey of the use of physical restraint in long-term care hospitals in Japan. AB - AIMS AND OBJECTIVES: To investigate the prevalence of physical restraints in the long-term care hospitals in Japan and to examine the factors of physical restraint use, including the specific skills/techniques that the staff use to minimise the restraints. Background. Despite the national efforts to nullify physical restraint, it is still prevalent in long-term care facilities in and out of Japan. More detailed information regarding what affects physical restraint is needed. DESIGN: Cross-sectional mail survey. METHOD: A questionnaire was sent to a nursing ward manager of the random sample of long-term care facilities in Japan. RESULTS: The average rate of physical restraint was 25.5%. Altogether, 81.0% of the restrained clients were under restraint for more than one month. The most prevalent method of restraint was bilateral bedrails, followed by the use of coveralls and gloves. Factors of restraint were different depending on the type of restraint, suggesting specific approaches are needed for specific type of restraint. CONCLUSIONS: Physical restraint is still prevalent in Japanese long term care hospitals, and nurses need to develop effective intervention approach to redesigning practice related to physical restraints. Specialised intervention approach seems needed depending on the types of restraint. RELEVANCE TO CLINICAL PRACTICE: Specific approach should be developed to minimise the physical restraint in long-term care hospitals in Japan. PMID- 22300268 TI - Panton-Valentine leucocidin-producing Staphylococcus aureus: redefining the significance of pyogenic skin infections. PMID- 22300269 TI - Syntheses, structures, luminescence, and magnetic properties of one-dimensional lanthanide coordination polymers with a rigid 2,2'-bipyridine-3,3',6,6' tetracarboxylic acid ligand. AB - A series of novel one-dimensional (1-D) lanthanide coordination polymers (CPs), with the general formula {[Ln(bptcH)(H(2)O)(2)].H(2)O}(n) (Ln = Nd(III) (1), Eu(III) (2), Gd(III) (3), Tb(III) (4), Dy(III) (5), Ho(III) (6), or Er(III) (7)) have been synthesized by the solvothermal reactions of the corresponding lanthanide(III) picrates and 2,2'-bipyridine-3,3',6,6'-tetracarboxylic acid (bptcH(4)). These polymers have been structurally characterized by single-crystal X-ray diffraction, IR, PXRD, thermogravimetric (TGA), and elemental analysis. Coordination polymers 1-7 are isostructural; they possess the same 3D supramolecular architectures and crystallize in triclinic space group P1. The frameworks constructed from dinuclear lanthanide building blocks exhibit one dimensional double-stranded looplike chain architectures, in which the bptcH(3-) ions adopted hexadentate coordination modes. The Eu(III) (2) and Tb(III) (4) polymers exhibit characteristic photoluminescence in the visible region. The magnetic properties of polymers 2, 3, and 5 have been investigated through the measurement of their magnetic susceptibilities over the temperature range of 1.8 300 K. PMID- 22300270 TI - Technology--a social change agent for global health. PMID- 22300272 TI - Hyperosmotic and isosmotic shrinkage differentially affect protein phosphorylation and ion transport. AB - In the present work, we compared the outcome of hyperosmotic and isosmotic shrinkage on ion transport and protein phosphorylation in C11-MDCK cells resembling intercalated cells from collecting ducts and in vascular smooth muscle cells (VSMC) from the rat aorta. Hyperosmotic shrinkage was triggered by cell exposure to hypertonic medium, whereas isosmotic shrinkage was evoked by cell transfer from an hypoosmotic to an isosmotic environment. Despite a similar cell volume decrease of 40%-50%, the consequences of hyperosmotic and isosmotic shrinkage on cellular functions were sharply different. In C11-MDCK and VSMC, hyperosmotic shrinkage completely inhibited Na(+),K(+)-ATPase and Na(+),P(i) cotransport. In contrast, in both types of cells isosmotic shrinkage slightly increased rather than suppressed Na(+),K(+)-ATPase and did not change Na(+),P(i) cotransport. In C11-MDCK cells, phosphorylation of JNK1/2 and Erk1/2 mitogen activated protein kinases was augmented in hyperosmotically shrunken cells by ~7- and 2-fold, respectively, but was not affected in cells subjected to isosmotic shrinkage. These results demonstrate that the data obtained in cells subjected to hyperosmotic shrinkage cannot be considered as sufficient proof implicating cell volume perturbations in the regulation of cellular functions under isosmotic conditions. PMID- 22300273 TI - Clinicopathologic study of E-cadherin/beta-catenin complex, and topoisomerase-II in a series of 71 liposarcoma cases. AB - BACKGROUND: To investigate the expression of E-cadherin, beta-catenin and topoisomerase-II alpha and examine their clinical relevance in liposarcomas. MATERIALS AND METHODS: The expression of E-cadherin, beta-catenin and topoisomerase II alpha was examined immunohistochemically on formalin-fixed paraffin-embedded tissue specimens from 71 patients who underwent surgical treatment for liposarcomas of the extremities or the retroperitoneum in two major cancer reference centres between 1990 and 2000. Detailed medical notes were available for all patients who were followed for median 82 months (range 5 to 215 months). Obtained expression data were weighted against clinical and pathology parameters of clinical relevance. RESULTS: Patients were mostly male (59%), median age was 56 years for the liposarcomas of the extremities and 60 years for the retroperitoneal liposarcomas. The tumours were of diverse histology, grade and size (median diameters 7 and 17 cm for tumours of the extremities and retroperitoneum respectively). Expression of beta-catenin protein was weakly detected in 15 cases (21.1%). Similarly weak expression of topoisomerase II-alpha was detected in 14 (19.7%) cases of which only two had more than 20% of tumor cells stained positive. E-cadherin was not detected in the studied cohort of liposarcomas. We did not detect associations between the expression of the above proteins by liposarcoma cells and clinical outcome. CONCLUSIONS: Liposarcomas do not express E-cadherin, which matches the absence of epithelioid differentiation in this sarcoma subtype, and have low topoisomerase II-alpha expression, which justifies to some extend their resistance to anthracycline-based chemotherapy. PMID- 22300274 TI - Dual signaling system with an extended-tetrathiafulvalene-phenanthroline dyad acting as an electrooptical cation chemosensor. AB - An efficient synthesis of unprecedented fused extended-tetrathiafulvalene dipyridoquinoxaline (exTTF-dpq) dyad is described through the Horner-Wardsworth Emmons olefination methodology from the dipyrido[3,2-a:2',3'-c] benzo[3,4]phenazine-11,16-quinone (NqPhen) ligand starting material. This exTTF dpq dyad is demonstrated to act as a dual redox and colorimetric sensor for cations exploiting the proximity between the redox tetrathiafulvalene and the optical phenanthroline detecting sites. Its ability for sensing cations from the d-group metal transitions (Fe(2+), Ni(2+), and Zn(2+)) and also with varied cations such as Ca(2+) and Pb(2+) is presented. PMID- 22300275 TI - A morpho-anatomical characterisation of Myrothamnus moschatus (Myrothamnaceae) under the aspect of desiccation tolerance. AB - Morpho-anatomical traits of the rarely studied dicotyledonous desiccation tolerant shrub Myrothamnus moschatus were examined and compared for the first time to Myrothamnus flabellifolius under the aspect of desiccation tolerance. Both species almost exclusively occur on rock outcrops and differ mainly in their geographic range and leaf morphology (fan-shaped in M. flabellifolius, lanceolate in M. moschatus) but have a very similar leaf and wood anatomy, except for the lack of hydathodes in M. moschatus. Both species adopt the parallel leaf venation of monocots, although this is more pronounced in M. moschatus. This provides a mechanical and protective advantage over the net venation pattern of most dicots and facilitates the reversible, drought-induced, accordion-like leaf contraction. The sclerenchyma, as a stabilising tissue, is mainly confined to vascular bundles in leaves of both species. Here, mechanical support seems to be less crucial for survival in long periods of drought than other morpho-anatomical traits (e.g. parallel leaf venation). PMID- 22300276 TI - Does a reduction in dialysate sodium improve blood pressure control in haemodialysis patients? AB - INTRODUCTION: There has been debate as to the value of lower sodium dialysates to control blood pressure in haemodialysis patients, as sodium is predominantly removed by ultrafiltration. METHODS: Re-audit of clinical practice following reduction in dialysate sodium concentration. RESULTS: Overall dialysate sodium concentration decreased from 138.9 +/- 1.7 to 137.8 +/- 1.7 mmol/L (mean +/- standard deviation), resulting in a reduction in pre- and post-dialysis mean arterial pressure (MAP) of 4 mmHg (from 100.6 +/- 15.6 to 97.1 +/- 15.6, P < 0.01 and from 91.7 +/- 15.6 to 87.1 +/- 14.6, P < 0.001 respectively), yet fewer patients were prescribed antihypertensives (49.6 vs 60.6%), and less antihypertensive medications/patient (mean 0.86 vs 1.05), ultrafiltration requirements (2.8% vs 3.2% body weight, P < 0.001), and symptomatic intradialytic hypotension (0.19 vs 0.28 episodes per week, P < 0.001). A multivariable model showed that for a dialysate sodium of 136 mmol/L, younger patients had higher MAP than older patients (0.35 mmHg lower MAP/year older; but with a dialysate sodium of 140 mmol/L, there was minimal association of MAP with age (0.07 mmHg higher MAP/year older). CONCLUSION: Change in clinical practice, amounting to a modest reduction in dialysate sodium was associated with a reduction not only in pre- and post-dialysis blood pressures, but also ultrafiltration requirements and symptomatic intradialytic hypotension. However, this effect on blood pressure was most marked for older patients and women, within minimal effects for younger patients, and lesser effects for men, suggesting that dialysate sodium reduction alone may help improve blood pressure control, but requires additional factors such as dietary sodium restriction to be effective in younger male patients. PMID- 22300277 TI - Hazardous components and health effects of atmospheric aerosol particles: reactive oxygen species, soot, polycyclic aromatic compounds and allergenic proteins. AB - This review outlines recent advances in the investigation of the chemical properties, molecular interactions and health effects of hazardous compounds in atmospheric aerosols, in particular reactive oxygen species (ROS), soot, polycyclic aromatic compounds (PACs) and allergenic proteins. Epidemiological studies show correlations between air particulate matter and adverse health effects of air pollution including allergy, asthma, cardiovascular and respiratory diseases, but the causative relations and mechanisms of interaction on the molecular level are still unclear. ROS generated by photochemical and heterogeneous reactions in the atmosphere seem to play a key role in aerosol health effects and provide a direct link between atmospheric and physiological multiphase processes. Soot and PACs can trigger formation of ROS in vivo, leading to inflammation and cellular damage. PACs as well as allergenic proteins are efficiently oxygenated and nitrated upon exposure to ozone and nitrogen dioxide, which leads to an enhancement of their toxicity and allergenicity. PMID- 22300278 TI - The image of people with intellectual disability in Taiwan newspapers. AB - BACKGROUND: There is limited research on the development of newspaper analysis about the images of people with ID in Chinese newspapers. The purpose of this study was: (a) to understand the general image of persons with ID presented in printed newspapers in Taiwan, and (b) to classify the various images of persons with ID and to measure the relative proportions among these classifications. METHOD: Articles from 2008 from the media databank UDNDATA were analysed by content analysis. RESULTS: Three main images were portrayed. The greatest number of articles revolved around the "dispirited" image (44.5%), followed by "needy" (32.7%), and "affirmative" (22.8%). Articles focused on families with a member with ID made up 20.8% of the total articles, and 81% of these stories had a negative theme. CONCLUSION: The pessimistic portrayal of people with ID is popular and newspapers may create stigma for people with ID in Taiwan. PMID- 22300279 TI - Separation, culture and identification of SD rat corpus cavernosal endothelial cells. AB - The aim of the study is to investigate the methods of separation, culture and identification of Sprague Dawley (SD) rat corpus cavernosal vascular endothelial cells (CCECs). Cavernosal tissues were isolated from male SD rats. Enzymatic digestion was applied to separate CCECs. Purified cells were obtained using immunomagnetic beads and flow cytometric cell sorting and subcultured in EMG-2 medium. The growth curve of CCECs was measured by the tetrazolium salt 3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The cells were identified by von Willebrand factor (vWF) using immunofluorescence, and the positive percentage of vWF expression was detected by flow cytometry. The monomorphic cobblestone-like cells were observed by microscopy. High purification was obtained using immunomagnetic beads. After 2 days of incubation, cells entered the logarithmic growth phase and reached a plateau on the fifth day. The vWF expression in cytoplasm was positive. The purity of cells was 95.8%, which was tested by flow cytometry. SD rat CCECs can be separated and cultured successfully by the method of enzymatic digestion, immunomagnetic beads and flow cytometric cell sorting. PMID- 22300283 TI - DNA barcoding of parasitic nematodes: is it kosher? AB - Nematode parasites were encountered in kosher-certified fish meat and roe, and the question was raised as to whether or not these food products were kosher as concerns food preparation standards-a matter that pertains to the identity and, by extension, the life cycle of the parasites. To ascertain the identities of parasitic nematodes, given the distorted or damaged nature of the specimens, molecular techniques were applied in the form of DNA barcoding. To our knowledge, this is the first application of this technique to an obviously cultural concern as opposed to one of health or economic significance. Results, based both on cytochrome c oxidase subunits I and II, suggested that the parasite species found in the fish products are anisakine species that do not inhabit the intestinal lumen of the fish hosts examined. Thus, there was no evidence of failure to adhere to food preparation practices consistent with the proscriptions of Orthodox Judaism. Notwithstanding the success of DNA barcoding in determining at least the higher taxonomic identities of the parasites, some shortcomings of the DNA barcoding pipeline as it pertains to nematode parasites were encountered; specifically, the paucity of data available for the DNA barcoding locus, even for very common nematode taxa. PMID- 22300281 TI - Luminal cholinergic signalling in airway lining fluid: a novel mechanism for activating chloride secretion via Ca2+-dependent Cl- and K+ channels. AB - BACKGROUND AND PURPOSE: Recent studies detected the expression of proteins involved in cholinergic metabolism in airway epithelial cells, although the function of this non-neuronal cholinergic system is not known in detail. Thus, this study focused on the effect of luminal ACh as a regulator of transepithelial ion transport in epithelial cells. EXPERIMENTAL APPROACH: RT-PCR experiments were performed using mouse tracheal epithelial cells for ChAT and organic cation transporter (OCT) transcripts. Components of tracheal airway lining fluid were analysed with desorption electrospray ionization (DESI) MS. Effects of nicotine on mouse tracheal epithelial ion transport were examined with Ussing-chamber experiments. KEY RESULTS: Transcripts encoding ChAT and OCT1-3 were detected in mouse tracheal epithelial cells. The DESI experiments identified ACh in the airway lining fluid. Luminal ACh induced an immediate, dose-dependent increase in the transepithelial ion current (EC50: 23.3 uM), characterized by a transient peak and sustained plateau current. This response was not affected by the Na+ channel inhibitor amiloride. The Cl--channel inhibitor niflumic acid or the K+ channel blocker Ba2+ attenuated the ACh effect. The calcium ionophore A23187 mimicked the ACh effect. Luminal nicotine or muscarine increased the ion current. Experiments with receptor gene-deficient animals revealed the participation of muscarinic receptor subtypes M1 and M3. CONCLUSIONS AND IMPLICATIONS: The presence of luminal ACh and activation of transepithelial ion currents by luminal ACh receptors identifies a novel non-neuronal cholinergic pathway in the airway lining fluid. This pathway could represent a novel drug target in the airways. PMID- 22300284 TI - Serum leptin, adiponectin, resistin and ghrelin levels in psoriatic patients treated with cyclosporin. AB - Cyclosporin has various effects on adipose tissue and glucose metabolism. This situation may lead to changes in serum levels of adipocyte-derived cytokines which have influence on the pathogenesis of psoriasis. The aim of this study was to evaluate the effect of cyclosporin treatment on some adipocyte-derived cytokines in psoriatic patients. This case-control study was performed between June 2009 and March 2010, at the Department of Dermatology of Meram School of Medicine. Serum leptin, adiponectin, resistin and ghrelin levels were assessed in 26 patients with psoriasis before and after cyclosporin treatment and body mass index-matched 26 healthy control subjects. The adipokines levels were compared between the groups. Serum leptin, ghrelin, resistin and adiponectin levels in patients with psoriasis before the treatment were higher than those of the control group but the differences were not statistically significant. A positive correlation between serum leptin and family history of psoriasis was detected (r = 0.398, P = 0.044). A strong negative correlation between the Psoriasis Area and Severity Index and serum ghrelin levels was seen (r = -0.52, P = 0.001) and there was a strong positive correlation between the Nail Psoriasis Severity Index and serum resistin levels (r = 0.62, P = 0.001). Following the treatment, a significant increase was seen in the serum level of adiponectin (P = 0.02) and resistin (P = 0.003). The correlations between the adipokines and the disease parameters before the treatment were lost after the treatment. Our results suggest that levels of some adipocyte-derived cytokines in psoriatic patients are affected by cyclosporin treatment. PMID- 22300285 TI - Association of small hydrophobic solute in presence of the osmolytes urea and trimethylamine-N-oxide. AB - Influences of two naturally occurring osmolytes, urea and trimethylamine-N-oxide (TMAO), on hydrophobic interactions of methane are investigated by performing molecular dynamics (MD) simulations. In this study, we have used two different models of methane: one is of single united site (UA), and the other contains 5 sites (AA). We observe that two methane models behave similarly in pure water and in aqueous osmolyte solutions except for the fact that AA model of methane behaves slight differently in aqueous binary urea solution. Our potentials of mean force (PMF) calculations followed by association constant estimation and cluster structure analyses suggest urea-induced enhancement of methane association for the methane AA model. For both models, we observe the dehydration of methane molecules in presence of osmolytes. We also find the collapse of the second shell of water by urea and water structure enhancement by TMAO molecules. Our preferential interaction parameter calculations show that in binary aqueous urea solution methane molecules are expelled by urea molecules and this effect is more pronounced for the AA model. On the other hand, in binary aqueous TMAO solution, methane prefers to interact more with TMAO than water. Our water orientational structure calculations show that the orientation of water molecules near to hydrophobic moiety is anisotropic and osmolytes have a negligible effect on it. We also observe the osmolyte-induced water-water hydrogen bond lifetime increase in the hydration shell of methane as well as in the subsequent layers. PMID- 22300286 TI - Serum lipocalin-2 levels are increased in patients with psoriasis. AB - The protein lipocalin (LCN)-2 is known to be related to insulin resistance, obesity and atherosclerotic diseases. Psoriasis is an inflammatory skin disease related to metabolic syndrome. The aim of this study was to examine the relationship between serum LCN2 levels and indicators for metabolic syndrome and inflammatory cytokine levels in patients with psoriasis. Serum LCN2 levels were measured in patients with psoriasis, atopic dermatitis (AD) or bullous pemphigoid (BP), and compared with those of healthy controls. Serum LCN2 levels were also compared with several indicators for metabolic syndrome, and with serum levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha, two markers of inflammation. Serum LCN2 levels in patients with psoriasis were significantly higher than those of healthy controls, but there was no significant correlation between serum LCN2 and body mass index. Serum LCN2 levels also correlated with serum IL-6 and TNF-alpha levels in patients with psoriasis. Serum LCN2 levels are a general indicator for increased inflammation in the patients with psoriasis. PMID- 22300287 TI - Pulp properties and their influence on enzymatic degradability. AB - Endoglucanase treatment of pulp for the adjustment of viscosity and the increase in pulp reactivity is a promising step in the concept for the beneficial production of dissolving pulps from paper grade pulps. To promote the commercial applicability of these enzymes, the influence of pulp properties such as carbohydrate composition, pulp type and cellulose morphology on the enzymatic degradability of a pulp was examined. High contents of hemicelluloses and lignin were shown to impair the accessibility of the cellulose to the enzymes. Due to the elevated swelling capacity of cellulose II, conversion of the cellulose morphology from I to II upon alkaline treatments showed a large increasing effect on the cellulose accessibility, and enzymatic degradability. Reactivity measurements of softwood sulfite pulps after enzymatic degradation and acid catalyzed hydrolysis, respectively, revealed elevated reactivity for the pulp after acid treatment. This is in contrast to effects of enzyme treatments reported for CCE treated kraft pulps. PMID- 22300288 TI - Inhibitory effect of ginsenoside-Rd on carrageenan-induced inflammation in rats. AB - A previous study reported that ginsenoside-Rd reduced the production of tumor necrosis factor-alpha by inhibiting nuclear factor-kappaB in lipopolysaccharide activated N9 microglia in vitro. The aim of the present study was to confirm the anti-inflammatory effects and mechanisms of ginsenoside-Rd in animal experiments involving acute inflammation. The results indicated that ginsenoside-Rd at doses ranging from 12.5 to 50 mg/kg i.m. significantly inhibited the swelling of hind paws in rats for 1-6 h after the carrageenan injection. The levels of proinflammatory cytokines and proinflammatory mediators were markedly reduced by ginsenoside-Rd. Ginsenoside-Rd, when administered intramuscularly at 12.5, 25, and 50 mg/kg doses, showed signicant inhibition of carrageenan-induced production of interleukin-1beta (6.91%, 45.75%, and 55.18%, respectively), tumor necrosis factor-alpha (37.99%, 56.39%, and 47.38%, respectively), prostaglandin E(2) (22.92%, 30.12%, and 36.36%, respectively), and nitric oxide (28.27%, 44.53%, and 53.42%, respectively). In addition, ginsenoside-Rd (12.5, 25, and 50 mg/kg i.m.) effectively decreased the levels of nuclear factor-kappaB (6.77%, 20.28%, and 41.03%, respectively) and phosphorylation of IkappaBalpha (13.23%, 26.92%, and 41.80%, respectively) in the carrageenan-inflamed paw tissues. These results suggest that ginsenoside-Rd has significant anti-inflammatory effects in vivo, which might be due to its blocking of the nuclear factor-kappaB signaling pathway. Thus, it may be possible to develop ginsenoside-Rd as a useful agent for inflammatory diseases. PMID- 22300290 TI - Subendocardial contractile impairment in chronic ischemic myocardium: assessment by strain analysis of 3T tagged CMR. AB - BACKGROUND: The purpose of this study was to quantify myocardial strain on the subendocardial and epicardial layers of the left ventricle (LV) using tagged cardiovascular magnetic resonance (CMR) and to investigate the transmural degree of contractile impairment in the chronic ischemic myocardium. METHODS: 3T tagged CMR was performed at rest in 12 patients with severe coronary artery disease who had been scheduled for coronary artery bypass grafting. Circumferential strain (C strain) at end-systole on subendocardial and epicardial layers was measured using the short-axis tagged images of the LV and available software (Intag; Osirix). The myocardial segment was divided into stenotic and non-stenotic segments by invasive coronary angiography, and ischemic and non-ischemic segments by stress myocardial perfusion scintigraphy. The difference in C-strain between the two groups was analyzed using the Mann-Whitney U-test. The diagnostic capability of C strain was analyzed using receiver operating characteristics analysis. RESULTS: The absolute subendocardial C-strain was significantly lower for stenotic (-7.5 +/- 12.6%) than non-stenotic segment (-18.8 +/- 10.2%, p < 0.0001). There was no difference in epicardial C-strain between the two groups. Use of cutoff thresholds for subendocardial C-strain differentiated stenotic segments from non stenotic segments with a sensitivity of 77%, a specificity of 70%, and areas under the curve (AUC) of 0.76. The absolute subendocardial C-strain was significantly lower for ischemic (-6.7 +/- 13.1%) than non-ischemic segments ( 21.6 +/- 7.0%, p < 0.0001). The absolute epicardial C-strain was also significantly lower for ischemic (-5.1 +/- 7.8%) than non-ischemic segments (-9.6 +/- 9.1%, p < 0.05). Use of cutoff thresholds for subendocardial C-strain differentiated ischemic segments from non-ischemic segments with sensitivities of 86%, specificities of 84%, and AUC of 0.86. CONCLUSIONS: Analysis of tagged CMR can non-invasively demonstrate predominant impairment of subendocardial strain in the chronic ischemic myocardium at rest. PMID- 22300291 TI - Push-pull macrocycles: donor-acceptor compounds with paired linearly conjugated or cross-conjugated pathways. AB - Two-dimensional pi-systems are of current interest in the design of functional organic molecules, exhibiting unique behavior for applications in organic electronics, single-molecule devices, and sensing. Here we describe the synthesis and characterization of "push-pull macrocycles": electron-rich and electron-poor moieties linked by a pair of (matched) conjugated bridges. We have developed a two-component macrocyclization strategy that allows these structures to be synthesized with efficiencies comparable to acyclic donor-bridge-acceptor systems. Compounds with both cross-conjugated (m-phenylene) and linearly conjugated (2,5-thiophene) bridges have been prepared. As expected, the compounds undergo excitation to locally excited states followed by fluorescence from charge transfer states. The m-phenylene-based systems exhibit slower charge recombination rates presumably due to reduced electronic coupling through the cross-conjugated bridges. Interestingly, pairing the linearly conjugated 2,5 thiophene bridges also slows charge recombination. DFT calculations of frontier molecular orbitals show that the direct HOMO-LUMO transition is polarized orthogonal to the axis of charge transfer for these symmetrical macrocyclic architectures, reducing the electronic coupling. We believe the push-pull macrocycle design may be useful in engineering functional frontier molecular orbital symmetries. PMID- 22300292 TI - Pilot randomized trial of a nanopulse retinal laser versus conventional photocoagulation for the treatment of diabetic macular oedema. AB - BACKGROUND: To assess the efficacy of a new nanopulse laser, retinal regeneration therapy for the treatment of diabetic macular oedema. DESIGN: Randomized, non-inferiority, trial. PARTICIPANTS: 20 eyes of 17 subjects in the retinal regeneration therapy group and 18 eyes of 14 subjects in the conventional group were analysed. METHODS: The treatment group received retinal regeneration therapy laser, and the control group received photocoagulation. MAIN OUTCOME MEASURES: The primary outcome was the optical coherence tomography-measured change in central retinal thickness at 6 months. A secondary outcome was the change in logarithm of minimum angle of resolution visual acuity at 6 months. Non inferiority required the one-sided 95% confidence interval of the mean retinal thickness reduction after retinal regeneration therapy to be within 35 um of the reduction after control laser. RESULTS: When outliers were included in the dataset, the difference in retinal thickness reduction by analysis of covariance was 10.9 (standard deviation 17.6) mm in favour of the control laser. The difference between groups in retinal thickness reduction was 40.8 mm. If two extreme outliers were excluded, the difference was 5.6 (standard deviation 14.2) mm in favour of the retinal regeneration therapy laser, and the D optical coherence tomography was 18.5 mm. The visual acuity difference between groups was 0.059, meeting non-inferiority requirements. CONCLUSIONS: Although retinal thickness reduction was not unambiguously non-inferior, in the short-term, retinal regeneration therapy approximates the clinical efficacy of conventional photocoagulation, stabilizing visual acuity and providing motivation for larger trials assessing retinal regeneration therapy. PMID- 22300293 TI - Association of childhood family environments with the risk of social withdrawal ('hikikomori') in the community population in Japan. AB - AIMS: Hikikomori is a form of social withdrawal among those who retreat from social interaction for protracted periods of time. This study examines family related childhood factors for hikikomori using the retrospective data derived from a population-based survey. METHODS: We derived data from World Mental Health Survey Japan. The subjects of this study were community residents aged 20-49 years (n=708). Multiple logistic regression was applied to examine the association between the lifetime experience of hikikomori and childhood family environment, adjusting for sex, age, and respondents' history of common mental disorders. RESULTS: Father's high educational level (odds ratio [OR]=6.0, 95% confidence interval [CI]=1.6-22.9), mother's common mental disorders (OR=5.9, 95%CI=1.1-33.3), and mother's panic disorders (OR=6.6, 95%CI=1.1-39.1) were significantly and positively associated with hikikomori after controlling for respondents' sex, age, and history of mental disorders. CONCLUSIONS: Our findings suggest that hikikomori cases are more likely to occur in families where the parents have high levels of education. Maternal panic disorder may be another risk factor for children to develop hikikomori. PMID- 22300294 TI - Loxapine P-glycoprotein interactions in vitro. AB - The antipsychotic drugs risperidone, paliperidone, olanzapine, quetiapine, aripiprazole, clozapine, haloperidol, and chlorpromazine have been reported to have various degrees of interaction (substrate or inhibitor) with the multidrug resistance transporter, P-glycoprotein (P-gp). An interaction of the antipsychotic drug loxapine with P-gp was recently reported, but an IC50 value was not determined. Loxapine (as the succinate salt) was evaluated as a P-gp substrate, and inhibitor of P-gp mediated transport of digoxin in vitro in Caco-2 cells. Loxapine was not a substrate for P-gp but did exhibit weak-to-moderate inhibition (IC50 = 9.1 MUM). Since the typical steady state maximal plasma concentrations of loxapine in clinical use have been reported to be in the nanomolar range, pharmacokinetic interactions due to the inhibition of P-gp activity are not expected. PMID- 22300295 TI - New insights on dimethylaminoethanol (DMAE) features as a free radical scavenger. AB - Recently, a number of synthetic drugs used in a variety of therapeutic indications have been reported to have antiaging effects. Among them, Dimethylaminoethanol (DMAE), an anologue of dietylaminoethanol, is a precursor of choline, which in turn allows the brain to optimize the production of acetylcholine that is a primary neurotransmitter involved in learning and memory. The data presented here includes new information on the ability of the compound to scavenge specific free radicals, assessed by Electron Spectroscopic Resonance (EPR), to further analyze the role of DMAE as an antioxidant. DMAE ability to directly react with hydroxyl, ascorbyl and lipid radicals was tested employing in vitro assays, and related to the supplemented dose of the compound. PMID- 22300296 TI - Nociceptive and pro-inflammatory effects of dimethylallyl pyrophosphate via TRPV4 activation. AB - BACKGROUND AND PURPOSE: Sensory neuronal and epidermal transient receptor potential ion channels (TRPs) serve an important role as pain sensor molecules. While many natural and synthetic ligands for sensory TRPs have been identified, little is known about the endogenous activator for TRPV4. Recently, we reported that endogenous metabolites produced by the mevalonate pathway regulate the activities of sensory neuronal TRPs. Here, we show that dimethylallyl pyrophosphate (DMAPP), a substance produced by the same pathway is an activator of TRPV4. EXPERIMENTAL APPROACH: We examined the effects of DMAPP on sensory TRPs using Ca2+ imaging and whole-cell electrophysiology experiments with a heterologous expression system (HEK293T cells transfected with individual TRP channels), cultured sensory neurons and keratinocytes. We then evaluated nociceptive behavioural and inflammatory changes upon DMAPP administration in mice in vivo. KEY RESULTS: In the HEK cell heterologous expression system, cultured sensory neurons and keratinocytes, uM concentrations of DMAPP activated TRPV4. Agonistic and antagonistic potencies of DMAPP for other sensory TRP channels were examined and activation of TRPV3 by camphor was found to be inhibited by DMAPP. In vivo assays, intraplantar injection of DMAPP acutely elicited nociceptive flinches that were prevented by pretreatment with TRPV4 blockers, indicating that DMAPP is a novel pain-producing molecule through TRPV4 activation. Further, DMAPP induced acute inflammation and noxious mechanical hypersensitivities in a TRPV4-dependent manner. CONCLUSIONS AND IMPLICATIONS: Overall, we found a novel sensory TRP acting metabolite and suggest that its use may help to elucidate the physiological role of TRPV4 in nociception and associated inflammation. PMID- 22300298 TI - Treatment of ivermectin overdose in a miniature Shetland Pony using intravenous administration of a lipid emulsion. PMID- 22300299 TI - Seroprevalence of Toxoplasma gondii infection in dogs in Jiangsu Province, eastern China. AB - There is a lack of epidemiological data on Toxoplasma gondii infection in dogs from eastern China. In the present study, serum samples from 288 dogs were collected from Xuzhou, Huaiyin, and Yianchen in Jiangsu Province, eastern China, in August 2010; T. gondii antibodies were assayed by a modified agglutination test (MAT). Antibodies to T. gondii were found in 62 of 288 (21.5%) with MAT titers of 1?25 in 21 dogs, 1?50 in 15, 1?100 in 11, 1?200 in 6, and 1?400 and above in 3 dogs. The seroprevalence in >=3-yr-old dogs was significantly higher (P < 0.05) than that in dogs less than 3-yr-old. The results of the present study indicated that infection with T. gondii in household dogs in Jiangsu Province is a public health concern. PMID- 22300300 TI - Spectroscopy and kinetics of tyrosinase catalyzed trans-resveratrol oxidation. AB - The spectroscopy and kinetics of the tyrosinase catalyzed trans-resveratrol oxidation were investigated by measuring both UV-vis absorption spectra over the 200-500 nm range and Raman spectra over the 600-1800 cm(-1) region. Room temperature UV-vis absorption spectra, as a function of time, showed the presence of two isosbestic points located at lambda(1) = 270 nm and lambda(2) = 345.5 nm delimiting two different regions: the reactant region around 300 nm, where the absorption decreased with time, and the product region over the low wavelength (lambda < 260 nm) and high wavelength (lambda > 390 nm) wavelength zone in which the absorption increased with time until, in both cases, constant values were achieved. A first-order kinetics was deduced with a rate coefficient of k(1) = (0.10 +/- 0.001) min(-1), which turned out to be independent of substrate concentration over the 50-5 MUM range; a feature that was rationalized by invoking the limiting case of the Michaelis-Menten scheme appropriate for substrate concentration much lower than the respective Michaelis constant. The observation of the distinct resonance enhanced Raman lines, specifically those peaking at 830 cm(-1), 753 cm(-1), and 642 cm(-1) together with their time evolution, permitted us to gain insight into some crucial features and steps of the catalytic reaction. Namely, that the formation of the so-called trans resveratrol and tyrosinase (S)P complex with its O-O bridge plays a crucial role in the first steps of this enzymatic reaction and that the hydroxylation of the ortho C-H bond of the trans-resveratrol OH group occurs after O-O bond cleavage in the tyrosinase active site. The present study makes clear that a class of potential inhibitors of tyrosinase can be found in compounds able to bind the two Cu (II) ions of the enzyme bidentate form. PMID- 22300301 TI - Dermatoscopy for monitoring treatment of actinic keratosis with imiquimod. PMID- 22300302 TI - Calpastatin overexpression in the skeletal muscle of mice prevents clenbuterol induced muscle hypertrophy and phenotypic shift. AB - Accumulating evidence suggests that the calpain/calpastatin system is involved in skeletal muscle remodelling induced by beta(2) -adrenoceptor agonist treatment. In addition to other pathways, the Akt/mammalian target of rapamycin (mTOR) pathway, controlling protein synthesis, and the calcium/calmodulin-dependent protein kinase 2 (CamK2) and AMP-activated protein kinase (AMPK) pathways, recently identified as calpain substrates, could be relevant in beta(2) adrenoceptor agonist-induced skeletal muscle remodelling. In the present study we investigated muscle hypertrophy and phenotypic shifts, as well as the molecular response of components of the Akt/mTOR pathway (i.e. Akt, eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), ribosomal protein S6 (rpS6), CamK2 and AMPK), in response to calpastatin overexpression in the skeletal muscle of mice treated with 1 mg/kg per day clenbuterol for 21 days. Using gene electrotransfer of a calpastatin expression vector into the tibialis anterior of adult mice, we found that calpastatin overexpression attenuates muscle hypertrophy and phenotypic shifts induced by clenbuterol treatment. At the molecular level, calpastatin overexpression markedly decreased calpain activity, but was ineffective in altering the phosphorylation of Akt, 4E-BP1 and rpS6. In contrast, calpastatin overexpression increased the protein expression of both total AMPK and total CamK2. In conclusion, the results support the contention that the calpain/calpastatin system plays a crucial role in skeletal muscle hypertrophy and phenotypic shifts under chronic clenbuterol treatment, with AMPK and CamK2 probably playing a minor role. Moreover, the calpastatin-induced inhibition of hypertrophy under clenbuterol treatment was not related to a decreased mTOR dependent initiation of protein translation. PMID- 22300303 TI - Coping in relationships: the interplay between individual and dyadic coping and their effects on relationship satisfaction. AB - The main aim of the present study was to determine how individual and dyadic coping efforts are related in the context of relationships. This aim was achieved by studying partners simultaneously and taking into account the interdependent nature of couple data. Specifically tested was whether dyadic coping mediates the influence of individual coping, and whether there is a mutual influence of partners' dyadic coping. Cross-sectional data of 240 German couples were analyzed using structural equation modeling. Results indicated that dyadic coping is a stronger predictor of relationship satisfaction than individual coping, and that it mediates the individual coping efforts. Mutual influence could be demonstrated for pragmatic coping but not for emotional coping. This research highlights the importance of dyadic coping by focusing on the ways in which couples cope together. PMID- 22300304 TI - Drastically lowered protein adsorption on microbicidal hydrophobic/hydrophilic polyelectrolyte multilayers. AB - Polyelectrolyte multilayer films assembled from a hydrophobic N-alkylated polyethylenimine and a hydrophilic polyacrylate were discovered to exhibit strong antifouling, as well as antimicrobial, activities. Surfaces coated with these layer-by-layer (LbL) films, which range from 6 to 10 bilayers (up to 45 nm in thickness), adsorbed up to 20 times less protein from blood plasma than the uncoated controls. The dependence of the antifouling activity on the nature of the polycation, as well as on assembly conditions and the number of layers in the LbL films, was investigated. Changing the hydrophobicity of the polycation altered the surface composition and the resistance to protein adsorption of the LbL films. Importantly, this resistance was greater for coated surfaces with the polyanion on top; for these films, the average zeta potential pointed to a near neutral surface charge, thus, presumably minimizing their electrostatic interactions with the protein. The film surface exhibited a large contact angle hysteresis, indicating a heterogeneous topology likely due to the existence of hydrophobic-hydrophilic regions on the surface. Scanning electron micrographs of the film surface revealed the existence of nanoscale domains. We hypothesize that the existence of hydrophobic/hydrophilic nanodomains, as well as surface charge neutrality, contributes to the LbL film's resistance to protein adsorption. PMID- 22300305 TI - Confined space emergency response: assessing employer and fire department practices. AB - An emergency response plan for industrial permit-required confined space entry is essential for employee safety and is legally required. Maintaining a trained confined space rescue team, however, is costly and technically challenging. Some employers turn to public fire departments to meet their emergency response requirements. The confined space emergency response practices of employers and fire departments have not been previously assessed. We present (1) federal data on the U.S. occurrence between 1992 and 2005 of confined space fatal incidents involving toxic and/or oxygen-deficient atmospheres; (2) survey data from 21 large companies on permit-required confined space emergency response practices; (3) data on fire department arrival times; and (4) estimates by 10 senior fire officers of fire department rescue times for confined space incidents. Between 1992 and 2005, 431 confined space incidents that met the case definition claimed 530 lives, or about 0.63% of the 84,446 all-cause U.S. occupational fatal injuries that occurred during this period. Eighty-seven (20%) incidents resulted in multiple fatalities. Twelve (57%) of 21 surveyed companies reported that they relied on the fire department for permit-required confined space emergency response. Median fire department arrival times were about 5 min for engines and 7 min for technical rescue units. Fire department confined space rescue time estimates ranged from 48 to 123 min and increased to 70 and 173 min when hazardous materials were present. The study illustrates that (1) confined space incidents represent a small but continuing source of fatal occupational injuries in the United States; (2) a sizeable portion of employers may be relying on public fire departments for permit-required confined space emergency response; and (3) in the event of a life-threatening emergency, fire departments usually are not able to effect a confined space rescue in a timely manner. We propose that the appropriate role for the fire department is to support a properly trained and equipped on-site rescue team and to provide advanced life support intervention following extrication and during ambulance transportation. PMID- 22300306 TI - Oxido-bridged di-, tri-, and tetra-nuclear iron complexes bearing bis(trimethylsilyl)amide and thiolate ligands. AB - A series of di-, tri-, and tetra-nuclear iron-oxido clusters with bis(trimethylsilyl)amide and thiolate ligands were synthesized from the reactions of Fe{N(SiMe(3))(2)}(2) (1) with 1 equiv of thiol HSR (R = C(6)H(5) (Ph), 4 (t)BuC(6)H(4), 2,6-Ph(2)C(6)H(3) (Dpp), 2,4,6-(i)Pr(3)C(6)H(2) (Tip)) and subsequent treatment with O(2). The trinuclear clusters [{(Me(3)Si)(2)N}Fe](3)(MU(3)-O){MU-S(4-RC(6)H(4))}(3) (R = H (3a), (t)Bu (3b)) were obtained from the reactions of 1 with HSPh or HS(4-(t)BuC(6)H(4)) and O(2), while we isolated a tetranuclear cluster [{(Me(3)Si)(2)N}(2)Fe(2)(MU SDpp)](2)(MU(3)-O)(2) (4) as crystals from an analogous reaction with HSDpp. Treatment of a tertrahydrofuran (THF) solution of 1 with HSTip and O(2) resulted in the formation of a dinuclear complex [{(Me(3)Si)(2)N}(TipS)(THF)Fe](2)(MU-O) (5). The molecular structures of these complexes have been determined by X-ray crystallographic analysis. PMID- 22300307 TI - Aripiprazole may be free from tachyphylaxis: preliminary findings. AB - Loss of antipsychotic efficacy (tachyphylaxis), possibly linked to an increase in D2 receptor number and sensitivity, is a significant impediment to treatment in chronic schizophrenia patients. Animal studies, however, suggest that aripiprazole may be free from tachyphylaxis. The aim of the present study was to investigate this hypothesis. In this preliminary study, aripiprazole-treated patients were retrospectively investigated for the presence or absence of tachyphylaxis. Clinical Global Impression-Improvement (CGI-I) scores did not significantly change and there was no significant association of CGI scores with fixed dose duration. This suggests that aripiprazole may be free from tachyphylaxis. PMID- 22300308 TI - Enantioselective synthesis of cocaine C-1 analogues using sulfinimines (N sulfinyl imines). AB - The first examples of cocaine analogues having substituents (methyl, ethyl, n propyl, n-pentyl, and phenyl) at the C-1 position of the cocaine tropane skeleton were prepared by heating sulfinimine-derived alpha,beta-unsaturated pyrrolidine nitrones. In the presence of the Lewis acid Al(O(t)Bu)(3) the nitrones undergo an intramolecular [3 + 2] cycloaddition to give tricyclic isoxazolidines that were transformed in three steps to the cocaine analogues. In the absence of the Lewis acid, lactams were formed resulting from rearrangement of the nitrone to an oxaziridine. A novel Pd- and base-promoted rearrangement of methanesulfonate salts of isoxazolidine to bridge bicyclic[4.2.1]isoxazolidines was discovered. PMID- 22300309 TI - Extreme strain localization and sliding friction in physically associating polymer gels. AB - Model physically associating gels deformed in shear over a wide range of reduced rates displayed evidence of strain localization. The nonlinear stress responses and inhomogeneous velocity profiles observed during shear rheometry coupled with particle tracking velocimetry were associated with the occurrence of rate dependent banding and fracture-like responses in the gel. Scaling law analysis from traditional sliding friction studies suggests that, at the molecular level, deformation is confined to a shear zone with thickness comparable to the mesh size of the gel, the smallest structurally relevant length scale in the gel. PMID- 22300310 TI - Close link between development and function of gamma-delta T cells. AB - Murine gammadelta T cells develop as the first T-cell lineage within the fetal thymus and disproportionately localize in mucosal tissues such as lung, skin, uterus, and intestine of adult mice. These unique developmental features and distribution patterns of gammadelta T cells enable rapid functioning against various insults from pathogens. gammadelta T cells are also able to respond to local inflammation and consequently regulate the pathogenesis of autoimmune disorders and development of tumors in mice and humans. Hence, it is clinically important to understand the mechanisms that regulate gammadelta T cell functions. Recent evidence has shown that generations of effector gammadelta T cell subsets producing IFN-gamma, IL-4, and IL-17 are programmed in the murine thymus before their migration to peripheral tissues. This review outlines our current understanding of the development and function of gammadelta T cells as they influence both innate and acquired immunity. PMID- 22300312 TI - Preface: RECOMB Systems Biology, Regulatory Genomics, and DREAM 2011 special issue. PMID- 22300311 TI - Predictors of long-term visual outcome after chemoreduction for management of intraocular retinoblastoma. AB - BACKGROUND: To determine the predictors of long-term visual outcome after chemoreduction for management of intraocular retinoblastoma. DESIGN: Retrospective case series. PARTICIPANTS: One hundred and forty eyes of 96 new retinoblastoma patients. METHODS: The clinical records were reviewed for demographical profile, tumour characteristics, treatment methods, treatment side effects and final visual outcome. Multivariate analysis was used to evaluate factors predictive of final visual acuity. MAIN OUTCOME MEASURE: The clinical data were analysed for main outcome measures of good vision (visual acuity >=6/12) or ambulatory vision (visual acuity >=6/60). The correlation among predictor variables was determined using Pearson's product moment correlation for continuous variables, and t-test and analysis of variance test for categorical baseline variables. RESULTS: Follow-up ranged from 2 years to 14 years (median 75 months). The final mean logarithm of minimum angle of resolution visual acuity was 0.79. Ambulatory vision (>=6/60) was achieved in 100 of 140 (71%) eyes, and vision of >=6/12 was seen in 52 eyes (37%). Extrafoveolar tumour and greater number of tumours in the eye were the only predictors of visual acuity >=20/40. Greater number of tumours correlated with smaller mean basal tumour diameter. The mean basal tumour diameter was 9.8 mm in eyes with multiple tumours and 12.2 mm in eyes with single tumours (P = 0.03). CONCLUSION: Long-term ambulatory vision (>=6/60) was achieved in the majority (71%) of retinoblastoma containing eyes not requiring enucleation after treatment with chemoreduction and adjunctive therapy. Absence of foveolar involvement and greater number of tumours were the predictor of long- term visual outcome of 6/12 or better. PMID- 22300313 TI - Optimization approaches for the in silico discovery of optimal targets for gene over/underexpression. AB - Metabolic engineering (ME) efforts have been recently boosted by the increase in the number of annotated genomes and by the development of several genome-scale metabolic models for microbes of interest in industrial biotechnology. Based on these efforts, strain optimization methods have been proposed to reach the best set of genetic changes to apply to selected host microbes, in order to create strains that are able to overproduce metabolites of industrial interest. Previous work in strain optimization has been mostly based in finding sets of gene (or reaction) deletions that lead to desired phenotypes in computational simulations. In this work, we focus on enlarging the set of possible genetic changes, considering gene over and underexpression. A gene is considered under (over) expressed if its expression value is constrained to be significantly lower (higher) than the one in the wild-type strain, used as a reference. A method is proposed to propagate relative gene expression values to flux constraints over related reactions, making use of the available transcriptional/translational information. The algorithms chosen for the optimization tasks are metaheuristics such as Evolutionary Algorithms (EA) and Simulated Annealing (SA), based on previous successful work on gene knockout optimization. These methods were modified appropriately to accommodate the novel optimization tasks and were applied to study the optimization of succinic and lactic acid production using Escherichia coli as the host. The results are compared with previous ones obtained in gene knockout optimization, thus showing the usefulness of the approach. The methods proposed in this work were implemented in a novel plug-in for OptFlux, an open-source software framework for ME. Supplementary Material is available at www.liebertonline.com/cmb. PMID- 22300314 TI - Anti-cooperative and cooperative protein-protein interactions between TetR isoforms on synthetic enhancers. AB - Protein-protein interactions play an important role in determining the regulatory output of cis regulatory regions. In this work, we revisit the regulatory output functions recorded for the synthetic enhancers that contain binding sites for TetR. We use our thermodynamic model as an analysis tool to infer that two different types of interactions may take place between the TetR molecules. First, a strong mutually exclusive anti-cooperative interaction precludes the synthetic enhancer from being occupied by more than one AT (the aTc bound TetR isoform) protein, and a second weak cooperative interaction exists between the aTc-free TetR isoform (T). Consequently, this work highlights the power of the synthetic enhancer approach as a tool for studying protein-protein interactions via an experimentally verifiable prediction for the general mode of binding of the TetR repressor. PMID- 22300315 TI - Binding profiles of chromatin-modifying proteins are predictive for transcriptional activity and promoter-proximal pausing. AB - The establishment and maintenance of proper gene expression patterns is essential for stable cell differentiation. Using unsupervised learning techniques, chromatin states have been linked to discrete gene expression states, but these models cannot predict continuous gene expression levels, nor do they reveal detailed insight into the chromatin-based control of gene expression. Here, we employ regularized regression techniques to link, in a quantitative manner, binding profiles of chromatin proteins to gene expression levels and promoter proximal pausing of RNA polymerase II in Drosophila melanogaster on a genome-wide scale. We apply stability selection to reliably detect interactions of chromatin features and predict several known, suggested, and novel proteins and protein pairs as transcriptional activators or repressors. Our integrative analysis reveals new insights into the complex interplay of transcriptional regulators in the context of gene expression. Supplementary Material is available at www.libertonline.com/cmb. PMID- 22300316 TI - Fast, sensitive discovery of conserved genome-wide motifs. AB - Regulatory sites that control gene expression are essential to the proper functioning of cells, and identifying them is critical for modeling regulatory networks. We have developed Magma (Multiple Aligner of Genomic Multiple Alignments), a software tool for multiple species, multiple gene motif discovery. Magma identifies putative regulatory sites that are conserved across multiple species and occur near multiple genes throughout a reference genome. Magma takes as input multiple alignments that can include gaps. It uses efficient clustering methods that make it about 70 times faster than PhyloNet, a previous program for this task, with slightly greater sensitivity. We ran Magma on all non-coding DNA conserved between Caenorhabditis elegans and five additional species, about 70 Mbp in total, in <4 h. We obtained 2,309 motifs with lengths of 6-20 bp, each occurring at least 10 times throughout the genome, which collectively covered about 566 kbp of the genomes, approximately 0.8% of the input. Predicted sites occurred in all types of non-coding sequence but were especially enriched in the promoter regions. Comparisons to several experimental datasets show that Magma motifs correspond to a variety of known regulatory motifs. PMID- 22300317 TI - Structural bistability of the GAL regulatory network and characterization of its domains of attraction. AB - Bistability is a system-level property, exploited by many biomolecular interaction networks as a key mechanism to accomplish different cellular functions (e.g., differentiation, cell cycle, switch-like response to external stimuli). Bistability has also been experimentally found to occur in the regulatory network of the galactose metabolic pathway in the model organism Saccharomyces cerevisiae. In this yeast, bistability generates a persistent memory of the type of carbon source available in the extracellular medium: under the same experimental conditions, cells previously grown with different nutrients generate different responses and get stably locked into two distinct steady states. The molecular interactions of the GAL regulatory network have been thoroughly dissected through wet-lab experiments; thus, this system provides a formidable benchmark to our ability to characterize and reproduce in silico the behavior of bistable biological systems. To this aim, a number of models have been proposed in the literature; however, we found that they are not able to replicate the persistent memory behavior observed in (Acar et al., 2005 ). The present study proposes a novel model of the GAL regulatory network, which, in addition to reproducing in silico the experimental findings, can be formally analyzed for structural multistability of the network, using chemical reaction network theory (CRNT), and allows the characterization of the domains of attraction (DA). This work provides further insights into the GAL system and proposes an easily generalizable approach to the study of bistability-associated behaviors in biological systems. PMID- 22300318 TI - Large-scale elucidation of drug response pathways in humans. AB - Elucidating signaling pathways is a fundamental step in understanding cellular processes and developing new therapeutic strategies. Here we introduce a method for the large-scale elucidation of signaling pathways involved in cellular response to drugs. Combining drug targets, drug response expression profiles, and the human physical interaction network, we infer 99 human drug response pathways and study their properties. Based on the newly inferred pathways, we develop a pathway-based drug-drug similarity measure and compare it to two common, gold standard drug-drug similarity measures. Remarkably, our measure provides better correspondence to these gold standards than similarity measures that are based on associations between drugs and known pathways, or on drug-specific gene expression profiles. It further improves the prediction of drug side effects and indications, elucidating specific response pathways that may be associated with these drug properties. Supplementary Material for this article is available at www.liebertonline.com/cmb. PMID- 22300319 TI - An S-System Parameter Estimation Method (SPEM) for biological networks. AB - Advances in experimental biology, coupled with advances in computational power, bring new challenges to the interdisciplinary field of computational biology. One such broad challenge lies in the reverse engineering of gene networks, and goes from determining the structure of static networks, to reconstructing the dynamics of interactions from time series data. Here, we focus our attention on the latter area, and in particular, on parameterizing a dynamic network of oriented interactions between genes. By basing the parameterizing approach on a known power-law relationship model between connected genes (S-system), we are able to account for non-linearity in the network, without compromising the ability to analyze network characteristics. In this article, we introduce the S-System Parameter Estimation Method (SPEM). SPEM, a freely available R software package (http://www.picb.ac.cn/ClinicalGenomicNTW/temp3.html), takes gene expression data in time series and returns the network of interactions as a set of differential equations. The methods, which are presented and tested here, are shown to provide accurate results not only on synthetic data, but more importantly on real and therefore noisy by nature, biological data. In summary, SPEM shows high sensitivity and positive predicted values, as well as free availability and expansibility (because based on open source software). We expect these characteristics to make it a useful and broadly applicable software in the challenging reconstruction of dynamic gene networks. PMID- 22300320 TI - Dynamic modeling of miRNA-mediated feed-forward loops. AB - Given the important role of microRNAs (miRNAs) in genome-wide regulation of gene expression, increasing interest is devoted to mixed transcriptional and post transcriptional regulatory networks analyzing the combinatorial effect of transcription factors (TFs) and miRNAs on target genes. In particular, miRNAs are known to be involved in feed-forward loops (FFLs), where a TF regulates a miRNA and they both regulate a target gene. Different algorithms have been proposed to identify miRNA targets, based on pairing between the 5' region of the miRNA and the 3'UTR of the target gene, and correlation between miRNA host genes and target mRNA expression data. Here we propose a quantitative approach integrating an existing method for mixed FFL identification based on sequence analysis with differential equation modeling approach that permits us to select active FFLs based on their dynamics. Different models are assessed based on their ability to properly reproduce miRNA and mRNA expression data in terms of identification criteria, namely: goodness of fit, precision of the estimates, and comparison with submodels. In comparison with standard approaches based on correlation, our method improves in specificity. As a case study, we applied our method to adipogenic differentiation gene expression data providing potential novel players in this regulatory network. Supplementary Material for this article is available at www.liebertonline.com/cmb. PMID- 22300321 TI - Efficient manipulations of synonymous mutations for controlling translation rate: an analytical approach. AB - Gene translation is a central process in all living organism with important ramifications to almost every biomedical field. Previous systems evolutionary studies in the field have demonstrated that in many organisms coding sequence features undergo selection to optimize this process. In the current study, we report for the first time analytical proofs related to the various aspects of this process and its optimality. Among our results we show that coding sequences with mono- tonic increasing profiles of translation efficiency (i.e., with slower codons near the 5'UTR), mathematically optimize ribosomal allocation by minimizing the number of ribosomes needed for translating a codon per time unit. Thus, the genomic translation efficiency profile reported in previous studies for many organisms is optimal in this sense. In addition, we show that improving translation efficiency of a codon in a gene may result in a decrease in the translation rate of other genes, demonstrating that the relation between codon bias and protein translation rate is less trivial than was assumed before. Based on these observations we describe an efficient heuristic for designing coding sequences with specific translation efficiency and minimal ribosomal allocation for heterologous gene expression. We demonstrate how this heuristic can be used in biotechnology for engineering a heterologous gene before expressing it in a new host. PMID- 22300322 TI - A linearized constraint-based approach for modeling signaling networks. AB - With the unparalleled increase in the availability of biological data over the last couple of decades, accurate and computable models are becoming increasingly important for unraveling complex biological phenomena. Past efforts to model signaling networks have utilized various computational methods, including Boolean and constraint-based modeling (CBM) approaches. These approaches are based on solving mixed integer linear programs; hence, they may not scale up for the analysis of large networks and are not amenable for applications based on sampling the full spectrum of the solution space. Here we propose a new CBM approach that is fully linear and does not involve integer variables, thereby overcoming the aforementioned limitations. We describe a novel optimization procedure for model construction and demonstrate the utility of our approach on a reconstructed model of the human epidermal growth factor receptor (EGFR) pathway, spanning 322 species and 211 connections. We compare our model's predictions to experimental phosphorylation data and to the predictions inferred via an additional Boolean-based EGFR signaling model. Our results show high prediction accuracy (75%) and high similarity to the Boolean model. Considering the marked computational advantages in terms of scalability and sampling utilization obtained by having a linear mode, these results demonstrate the potential promise of this framework for the study of cellular signaling. PMID- 22300323 TI - MetaCluster 4.0: a novel binning algorithm for NGS reads and huge number of species. AB - Next-generation sequencing (NGS) technologies allow the sequencing of microbial communities directly from the environment without prior culturing. The output of environmental DNA sequencing consists of many reads from genomes of different unknown species, making the clustering together reads from the same (or similar) species (also known as binning) a crucial step. The difficulties of the binning problem are due to the following four factors: (1) the lack of reference genomes; (2) uneven abundance ratio of species; (3) short NGS reads; and (4) a large number of species (can be more than a hundred). None of the existing binning tools can handle all four factors. No tools, including both AbundanceBin and MetaCluster 3.0, have demonstrated reasonable performance on a sample with more than 20 species. In this article, we introduce MetaCluster 4.0, an unsupervised binning algorithm that can accurately (with about 80% precision and sensitivity in all cases and at least 90% in some cases) and efficiently bin short reads with varying abundance ratios and is able to handle datasets with 100 species. The novelty of MetaCluster 4.0 stems from solving a few important problems: how to divide reads into groups by a probabilistic approach, how to estimate the 4-mer distribution of each group, how to estimate the number of species, and how to modify MetaCluster 3.0 to handle a large number of species. We show that Meta Cluster 4.0 is effective for both simulated and real datasets. Supplementary Material is available at www.liebertonline.com/cmb. PMID- 22300324 TI - Transforming growth factor-beta impairs glucocorticoid activity in the A549 lung adenocarcinoma cell line. AB - BACKGROUND AND PURPOSE: The lung adenocarcinoma cell line, A549, undergoes epithelial-mesenchymal cell transition (EMT) in response to TGF-beta. Glucocorticoids do not prevent the EMT response, but TGF-beta induced resistance to the cytokine-regulatory action of glucocorticoids. We sought to characterize the impairment of glucocorticoid response in A549 cells. EXPERIMENTAL APPROACH: A549 cells were exposed to TGF-beta for up to 96 h before glucocorticoid treatment and challenge with IL-1alpha to assess glucocorticoid regulation of IL 6 and CXCL8 production. Nuclear localization of the glucocorticoid receptor alpha (GRalpha) was ascertained by immunofluorescence and Western blotting. Transactivation of the glucocorticoid response element (GRE) was measured with a transfected GRE-secreted human placental alkaline phosphatase reporter. KEY RESULTS: TGF-beta (40-400 pM) reduced the maximum inhibitory effect of dexamethasone on IL-1alpha-induced IL-6 and CXCL8 production. The impaired glucocorticoid response was detected with 4 h of TGF-beta (40 pM) exposure (and 4 h IL-1alpha to induce CXCL8 expression) and therefore was not secondary to EMT, a process that requires longer incubation periods and higher concentrations of TGF beta. TGF-beta also impaired dexamethasone regulation of granulocyte-macrophage colony-stimulating factor in thrombin-stimulated BEAS-2B epithelial cells. Impaired regulation of CXCL8 was associated with markedly reduced GRE transactivation and reduced induction of mRNA for IkappaBalpha, the glucocorticoid-inducible leucine zipper and the epithelial sodium channel (SCNN1A). The expression, cellular levels and nuclear localization of GRalpha were reduced by TGF-beta. CONCLUSIONS AND IMPLICATIONS: We have identified mechanisms underlying the impairment of responses to glucocorticoids by TGF-beta in the A549 and BEAS-2B cell lines. PMID- 22300325 TI - Policy challenges for the pediatric rheumatology workforce. PMID- 22300326 TI - Parasites of flier, Centrarchus macropterus, from prairie and channel habitats in the Okefenokee Swamp, Georgia. AB - Flier (Centrarchus macropterus: Centrarchidae) were collected from a channel habitat, a prairie habitat, and a boundary between the 2 habitat types in March 2009 and examined for parasites. Flier from the prairie site had a significantly lower abundance of Pterocleidus acer and a significantly higher abundance of Hysterothylaceum juveniles. Patterns of infracommunity similarity showed a distinct break between the 2 habitat types, with fish collected from the boundary site clustering with either channel or prairie communities, suggesting that the small home range of flier restricts the exposure of individuals to parasites. PMID- 22300328 TI - Experimental soybean meal intoxication in cattle. AB - BACKGROUND: Cattle are commonly fed soybean meal (SBM) and accidental intoxication sometimes occurs. OBJECTIVES: To describe the biologic and clinical features of SBM intoxication. ANIMALS: Four steers with ruminal cannula. METHODS: Controlled experimental trial. SBM was administered once at 1 and 2% of body weight (BW) via cannula at 2-month intervals. RESULTS: This study showed a 2 phase pathogenic course for 2% BW SBM intoxication. The 1st phase (until 10 hours post-administration) is restricted to ruminal modification with volatile fatty acid overproduction and moderate ruminal ammonia concentration. In the 2nd phase (12-22 hours post-administration), ruminal pH returned to initial values and marked ammonia accumulation occurred in blood, inducing severe metabolic alkalosis with hyperglycemia, hyperinsulinemia, and delayed aciduria (30-40 hours post-administration). Among the clinical signs, nervous signs were only observed during the period with increased plasma ammonia concentration. At 1% BW, ruminal and blood modifications were less pronounced than at 2% BW, and clinical signs were not observed. CONCLUSIONS AND CLINICAL RELEVANCE: Ammonia accumulation in blood during the second phase is the consequence of continued ammonia production, decreased carbohydrate fermentation, and overwhelming of hepatic detoxifying capacity. Because ammonia accumulation is associated with the clinical signs, treatment of SBM intoxication could be similar to treatment of urea intoxication, including rumenotomy, oral administration of cold water and vinegar, and measurement of ruminal pH. PMID- 22300330 TI - Conjunctival impression cytology, ocular surface and tear-film changes in patients with lichen planus. AB - BACKGROUND: Lichen planus (LP) is an immune-mediated chronic mucocutaneous disease. Rarely, LP affects the conjunctiva, resulting in conjunctival inflammation, cicatrization and scarring of the subepithelium and cornea, causing keratitis and keratoconjunctivitis sicca. To date, there has been no case-control study examining the ocular findings in LP. AIM: To assess ocular surface health and tear-film changes in patients with LP. METHODS: In total, 20 patients and 24 healthy controls were enrolled in the study. Ocular surface changes were evaluated by conjunctival impression cytology, while tear-film functions were measured by the Schirmer test, break-up time, and fluorescein and lissamine green scoring. RESULTS: There was a significant difference in Schirmer test results, conjunctival lissamine green staining scores, and conjunctival impression cytology grades between the groups. CONCLUSIONS: LP may cause ocular surface changes and reduction in tear production, therefore it seems reasonable to evaluate these patients for symptoms and signs of dry-eye disease. We consider that LP should be included in the differential diagnosis of dry-eye disease, as this has important therapeutic and prognostic implications. PMID- 22300329 TI - Significance of Group III and IV muscle afferents for the endurance exercising human. AB - 1. With the onset of dynamic whole-body exercise, contraction-induced mechanical and biochemical stimuli within locomotor muscle cause an increase in the discharge frequency of thinly myelinated (Group III) and unmyelinated (Group IV) nerve fibres located within the muscle. 2. These thin fibre muscle afferents project to various sites within the central nervous system and thereby substantially influence the exercising human. 3. First, Group III/IV muscle afferents are the afferent arm of cardiovascular and ventilatory reflex responses that are mediated in the nucleus tractus solitarius and the ventrolateral medulla. Therefore, neural feedback from working skeletal muscle is a vital component in providing a high capacity for endurance exercise because muscle perfusion and O2 delivery determine the fatigability of skeletal muscle. 4. Second, Group III/IV muscle afferents facilitate 'central fatigue' (failure, or unwillingness, of the central nervous system to 'drive' motoneurons) by exerting inhibitory influences on central motor drive during exercise. 5. Thus, Group III/IV muscle afferents play a substantial role in a human's susceptibility to fatigue and capacity for endurance exercise. PMID- 22300331 TI - The interface between inhibition of descending noradrenergic pain control pathways and negative affects in post-traumatic pain patients. AB - BACKGROUND: Animal studies have shown that surgical trauma activates the descending noradrenergic pathway. However, perioperative patients have decreased concentrations of noradrenaline (NA) in the cerebrospinal fluid (CSF). We proposed that the descending monoaminergic pathway is altered in post-traumatic pain patients and that CSF monoamine neurotransmitters may be more closely related to affective symptoms. We investigated the levels of monoamine neurotransmitters and assessed pain in these patients. METHODS: Patients were divided into a post-traumatic pain group, a pain-free group, a painful labor group, and a pain-free labor group. CSF was collected from all patients, and concentrations of NA, 3-methoxy-4-hydroxyphenylglycol (MHPG), dopamine, homovanillic acid, and 5-hydroxyindoleacetic acid (5-HIAA) were measured by high performance liquid chromatography. RESULTS: In the post-traumatic pain group, lumbar CSF concentrations of NA and MHPG were significantly decreased (P < 0.01) compared to the control group. The post-traumatic pain group displayed a significant negative correlation between NA and the respective total value of the short form of the McGill pain questionnaire (SF-MPQ), SF-MPQ (affective), and visual analog scale (r = -0.388, r = -0.433, and r = -0.367; P < 0.05). CONCLUSIONS: Post-traumatic pain patients demonstrated decreased concentrations of NAin CSF, indicating that descending noradrenergic pain control pathways may be inhibited. NA is more closely related to negative affects in post-traumatic pain patients. PMID- 22300332 TI - Reflections on having children in the future--interviews with highly educated women and men without children. AB - BACKGROUND: There is a trend to delay birth of the first child until the age at which female reproductive capacity has started to decrease. The aim of the present study was to explore how highly educated women and men reflected on future parenthood. METHODS: Twenty-two women and 18 men, who had started their professional career, were subjected to individual qualitative semi-structured interviews with qualitative content analysis guiding the analysis. RESULTS: All informants, except for three women, planned to have children when some important prerequisites were fulfilled. Women and men reflected in much the same way, and prerequisites for parenthood were being of reasonable age and having a partner in the same phase of life. A reasonable age was considered in relation to reproductive capacity, and both women and men expressed awareness of the natural decline in fertility at higher ages. Good living conditions with stable finances were also important. Parenthood was perceived as a challenge and a sacrifice but also as enriching life. Reasons for having children included being part of the future and settling down to build their own family. Many concluded that there would never be a perfect time for having children. CONCLUSION: Highly educated women and men reflect on various factors when considering family planning. Being of reasonable age and having good living conditions, in particular a sound personal economy, were important. Given their goals, it is not surprising that many postpone parenthood until ages when female reproductive capacity is decreased. PMID- 22300333 TI - Reference values of thirty-one frequently used laboratory markers for 75-year-old males and females. AB - BACKGROUND: We have previously reported reference values for common clinical chemistry tests in healthy 70-year-old males and females. We have now repeated this study 5 years later to establish reference values also at the age of 75. It is important to have adequate reference values for elderly patients as biological markers may change over time, and adequate reference values are essential for correct clinical decisions. METHODS: We have investigated 31 frequently used laboratory markers in 75-year-old males (n = 354) and females (n = 373) without diabetes. The 2.5 and 97.5 percentiles for these markers were calculated according to the recommendations of the International Federation of Clinical Chemistry. RESULTS: Reference values are reported for 75-year-old males and females for 31 frequently used laboratory markers. CONCLUSION: There were minor differences between reference intervals calculated with and without individuals with cardiovascular diseases. Several of the reference intervals differed from Scandinavian reference intervals based on younger individuals (Nordic Reference Interval Project). PMID- 22300334 TI - Clinical outcomes of a coping with stress training program among patients suffering from schizophrenia and schizoaffective disorder: a pilot study. AB - This study evaluated the clinical effects of an intervention aimed at enhancing specific self-efficacy for coping with stress (CSSE) among patients with psychosis. Fourteen patients, 21-60 years old, diagnosed with schizophrenia or schizoaffective disorder voluntarily participated and were randomly assigned to a training and a control group. The Brief Psychiatric Rating Scale-24 was used to assess psychotic symptoms (primary outcomes) at baseline, post-intervention, and three- and six-month follow-ups. The participants also completed self-reports on well-being and satisfaction with intervention outcomes (secondary outcomes) at post-intervention and at the two follow-up assessments. Trained patients showed a significant decrease in all measures of psychotic symptoms (for disorientation, not significant (NS); effect sizes up to d=4.80). This decline in symptoms remained significant at the follow-ups, with clinical enhancements on some of the subscales. By contrast, control participants showed no significant change in their symptoms. Short- and long-term overall well-being and satisfaction with outcomes were higher among the participants who received the training program. Our findings point out the relevance of enhancing CSSE among patients with psychosis, along with enhancing their coping skills for managing their illness. We conclude that CSSE training should be considered in future therapeutic interventions for psychotic disorders. PMID- 22300335 TI - Mechanisms and control of silk-based electrospinning. AB - Silk fibroin (SF) nanofibers, formed through electrospinning, have attractive utility in regenerative medicine due to the biocompatibility, mechanical properties, and tailorable degradability. The mechanism of SF electrospun nanofiber formation was studied to gain new insight into the formation and control of nanofibers. SF electrospinning solutions with different nanostructures (nanospheres or nanofilaments) were prepared by controlling the drying process during the preparation of regenerated SF films. Compared to SF nanospheres in solution, SF nanofilaments had better spinnability with lower viscosity when the concentration of silk protein was below 10%, indicating a critical role for SF morphology, and in particular, nanostructures, for the formation of electrospun fibers. More interesting, the diameter of electrospun fibers gradually increased from 50 to 300 nm as the concentration of SF nanofilaments in the solution increased from 6 to 12%, implying size control by simply adjusting SF nanostructure and concentration. Aside from process parameters investigated in previous studies, such as SF concentration, viscosity, and electrical potential, the present mechanism emphasizes significant influence of SF nanostructure on spinnability and diameter control of SF electrospun fibers, providing a controllable option for the preparation of silk-based electrospun scaffolds for biomaterials, drug delivery, and tissue engineering needs. PMID- 22300336 TI - Treatment of a congenital melanocytic nevus on the forehead with immediate tissue expansion technique: a three-year follow-up. AB - The aim of this case report was to determine the method and basic principles of immediate tissue expansion using a Foley catheter in the forehead region for treating a medium-sized congenital melanocytic nevus. A 4-year-old child presented with a supraorbitally located forehead congenital melanocytic nevus, close to the midline. Total excision and reconstruction with intraoperatively expanded forehead skin below the hairline was performed. Intraoperative tissue expansion using a Foley catheter allowed us to obtain expanded and enhanced local tissue, which had tissue characteristics similar to those of the forehead skin, and thus closure of a medium-sized defect without distorting important anatomic structures such as the brow and frontal hairline was possible. Of the two methods of tissue expansion, immediate expansion using a Foley catheter is a good alternative in single-stage reconstruction of head and neck defects because it has the advantage of omnidirectional expansion. PMID- 22300337 TI - Structure-correlation principles connecting ground state properties and reaction barrier heights for the Cope rearrangement of semibullvalenes. AB - A direct relationship exists between the properties of substituted semibullvalenes and their Cope rearrangement activation barrier. This unique correlation not only enables the determination of kinetic data from ground state information, but also provides a rationalization for the extent to which ground state properties are altered with respect to their "normal" values (i.e., that of their localized Lewis structure). Examination of electron density distribution, geometrical parameters, and J-coupling constant differences between canonical and Lewis structures deliver quantitative evidence for the structure-correlation principle. PMID- 22300338 TI - New fluorogenic sensors for Hg2+ ions: through-bond energy transfer from pentaquinone to rhodamine. AB - New pentaquinone derivatives 5 and 8 having rhodamine moieties have been designed and synthesized that undergo through-bond energy transfer (TBET) in the presence of Hg(2+) ions among the various cations (Cu(2+), Pb(2+), Fe(2+), Fe(3+), Zn(2+), Ni(2+), Cd(2+), Co(2+), Ag(+), Ba(2+), Mg(2+), K(+), Na(+), and Li(+)) tested in mixed aqueous media. PMID- 22300339 TI - Effect of lithium salt on the stability of dispersions of fumed silica in the ionic liquid BMImBF4. AB - We have investigated the stability and interactions in dispersions of colloidal fumed silica, Aerosil 200, and the ionic liquid 1-butyl-3-methylimidazolium tetraflouroborate (BMImBF(4)) as a function of the Li salt concentration (LiBF(4)). Photon correlation spectroscopy was used to study the aggregation behavior at low silica concentrations, and Raman spectroscopy was used to investigate the interactions in the ionic liquid and with the silica surface. We find that the addition of LiBF(4) increases the stability of the dispersions, with smaller agglomerates of silica particles and higher gelation concentrations in the presence of Li salt. The increased stability with the addition of Li salt is explained by the formation of a more stable solvation layer, where Li ions accumulate on the surface. This leads to an increased interaction between lithium ions and the BF(4)(-) anions in the solvation layer, as seen by Raman spectroscopy. Upon gelation, the Li ions are expelled from the surface because hydrogen bonding between the silica particles are formed. For both neat BMImBF(4) and Li-salt-doped BMImBF(4)/silica dispersions, a weak gel phase was found preceding the formation of a strong gel at slightly higher silica concentrations. PMID- 22300340 TI - Right hemispheric dominance and interhemispheric cooperation in gaze-triggered reflexive shift of attention. AB - AIMS: The neural substrate for the processing of gaze remains unknown. The aim of the present study was to clarify which hemisphere dominantly processes and whether bilateral hemispheres cooperate with each other in gaze-triggered reflexive shift of attention. METHODS: Twenty-eight normal subjects were tested. The non-predictive gaze cues were presented either in unilateral or bilateral visual fields. The subjects localized the target as soon as possible. RESULTS: Reaction times (RT) were shorter when gaze-cues were congruent toward than away from targets, whichever visual field they were presented in. RT were shorter in left than right visual field presentations. RT in mono-directional bilateral presentations were shorter than both of those in left and right presentations. When bi-directional bilateral cues were presented, RT were faster when valid cues were presented in the left than right visual fields. CONCLUSION: The right hemisphere appears to be dominant, and there is interhemispheric cooperation in gaze-triggered reflexive shift of attention. PMID- 22300341 TI - Fluids of the ocular surface: concepts, functions and physics. AB - General adoption of the ocular surface (OS) concept has advanced the therapy of the external eye. Fresh physical findings have prompted new concepts; examples taken from each section of the text are: (i) ever-present lipid sealant bridges the palpebral fissure capping the three-dimensional 'OS' sac. The muco-aqueous pool (MAP) is thus enclosed, secluded from atmosphere, evaporation mitigated. Hence, the OS is conceptually, a compartment. The term 'dacruon' (otherwise 'tear film') has been coined for the combined fluids of the OS, viz. lipid film and MAP. (ii) Investigative techniques of physics yield data on (say) surface tension and viscosity, and on functions such as anchorage of dacruon base to the varied mucosae of the OS, lubrication, renovation of intermarginal fluid layers as the eye opens after each blink, and refinement of optics and vision by the fluids attached to the cornea. (iii) Physical events in the opening eye produce the unique 'black line' phenomenon in which capillary force induces subsurface flows into thirsty menisci, bringing about parameniscal dark grooves, pupil-ward of each meniscus. Attenuation of fluorescein in the shallowed fluid gaps behind each groove makes the dye appear unilluminated ('black lines') relative to adjacent full-thickness MAP fluid glowing under cobalt-blue illumination. Isolated from cornea by grooves and gaps, the meniscal fluid cannot pass freely over the cornea. It therefore streams through the menisci to nasolacrimal outflow. PMID- 22300342 TI - Hydrogen sulfide-induced mechanical hyperalgesia and allodynia require activation of both Cav3.2 and TRPA1 channels in mice. AB - BACKGROUND AND PURPOSE: Hydrogen sulfide, a gasotransmitter, facilitates somatic pain signals via activation of Ca(v)3.2 T-type calcium channels in rats. Given evidence for the activation of transient receptor potential ankyrin-1 (TRPA1) channels by H(2)S, we asked whether TRPA1 channels, in addition to Ca(v)3.2 channels, contribute to the H(2)S-induced mechanical hyperalgesia and allodynia in mice. EXPERIMENTAL APPROACH: Mechanical hyperalgesia and allodynia were evaluated by the von Frey test in mice. Ca(v)3.2 or TRPA1 channels in the sensory neurons were silenced by repeated intrathecal administration of antisense oligodeoxynucleotides in mice. KEY RESULTS: Intraplantar administration of NaHS evoked hyperalgesia and allodynia in mice, an effect attenuated or abolished by NNC 55-0396 or mibefradil, T-type calcium channel blockers, and by ascorbic acid or zinc chloride, known to selectively inhibit Ca(v)3.2 channels, out of the three isoforms of T-type calcium channels. Silencing of Ca(v)3.2 channels in the sensory neurons also prevented the NaHS-induced hyperalgesia and allodynia in mice. The NaHS-induced hyperalgesia and allodynia in mice were significantly suppressed by AP18, a TRPA1 channel blocker, and by silencing of TRPA1 channels in the sensory neurons. CONCLUSIONS AND IMPLICATIONS: Mechanical hyperalgesia and allodynia induced by NaHS/H(2)S required activation of both Ca(v)3.2 and TRPA1 channels in mice. PMID- 22300344 TI - Maternal care in the soft tick Antricola marginatus. AB - Among spiders, scorpions, and whip spiders, a common type of maternal care consists of females carrying newly hatched offspring on their body for a few days until they are able to live independently. While this maternal care has been suggested to occur in different argasid tick species, it has been recorded only once, for Antricola marginatus in Cuba; however, this earlier record only superficially mentioned the occurrence of this behavior, with no further details. Here we report the occurrence of maternal care in the argasid tick A. marginatus under natural conditions in a cave at Yucatan, Mexico, where 8 A. marginatus females, while walking on bat guano, had their body entirely covered by a mean number of 305 +/- 112 conspecific unfed larvae (range: 105-466). Larvae covered the entire idiosoma of the female tick, where they were motionless or displayed just slight movement. This result substantially expands the number of unique characters that have been found only in Antricola spp. ticks, when compared to the other tick genera. Our findings also indicate that maternal care evolved independently in different taxa of Arachnida, since it has been reported for species of Araneae, Scorpiones, and Amblypygi, and here for an Acari species. PMID- 22300345 TI - Activation of human leukemic mast cell line LAD2 is modulated by dehydroleucodine and xanthatin. AB - The aim of the present study was to determine whether dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one inhibit the activation of human leukemic LAD2 mast cells induced by compound 48/80 or the calcium ionophore A23187. LAD2 cells were preincubated in the presence of test drugs and then challenged with the secretagogues. This study provides the first evidence in favor of the view that dehydroleucodine and xanthatin inhibit the degranulation of LAD2 cells, thus acting as human mast cell stabilizers. These molecules could be effective in the treatment of human diseases associated with inappropriate mast cell activation. PMID- 22300346 TI - Aberrant methylation and decreased expression of the RIZ1 gene are frequent in adult acute lymphoblastic leukemia of T-cell phenotype. AB - Retinoblastoma protein-interacting zinc finger, RIZ1, is a tumor suppressor gene that is inactivated in various solid tumors. However, the role of the RIZ1 gene has not been well examined in adult acute lymphoblastic leukemia (ALL). We analyzed the expression and promoter methylation status of the RIZ1 gene in patients with newly diagnosed ALL by quantitative real-time reverse transcription polymerase chain reaction (PCR) and methylation-specific PCR, respectively. RIZ1 expression in 67 cases of ALL (mean 1.043) was decreased compared with that in normal bone marrow (mean 1.471) (p = 0.030). Methylation was detected in 11 of 71 patients (15.5%) but not in healthy controls. Methylation was associated with decreased RIZ1 expression in many ALL cases examined, but this was not statistically significant. In T-ALL, RIZ1 methylation was more frequent (63.6%) than in B-ALL (6.7%) (p < 0.0001) and the decrease of RIZ1 expression was more significant than in B-ALL (p = 0.045). 5-Aza-2'-deoxycytidine treatment of MOLT-4 cells with RIZ1 methylation induced demethylation of RIZ1 and restoration of expression. Forced RIZ1 expression in T-ALL cell lines suppressed cell growth accompanied by G2/M arrest and apoptosis. No mutations were found by PCR-single strand conformation polymorphism analysis in hotspots of the gene. These results suggest that RIZ1 is inactivated in adult ALL, and this inactivation is associated with methylation in T-ALL. PMID- 22300347 TI - The role of bone marrow biopsy in Hodgkin lymphoma staging: "to be, or not to be, that is the question"? PMID- 22300348 TI - The potential benefits of participating in early-phase clinical trials in multiple myeloma: long-term remission in a patient with relapsed multiple myeloma treated with 90 cycles of lenalidomide and bortezomib. AB - We present the case of a woman with relapsed multiple myeloma (MM) who received combination lenalidomide and bortezomib therapy for 90 cycles followed by continuous lenalidomide monotherapy and has completed over 100 cycles of treatment to date. The patient was diagnosed with advanced-stage, symptomatic MM in 2001. Following a partial response (PR) to dexamethasone in combination with pamidronate and thalidomide, the patient underwent protocol-directed non myeloablative allogeneic bone marrow transplantation from her matched sibling donor the following year. In 2004, the patient relapsed and was enrolled in a phase I, dose-escalation trial of lenalidomide plus bortezomib for relapsed and refractory MM. After eight cycles of study treatment, the patient achieved a minimal response. The patient received a total of 90 cycles of treatment with lenalidomide 5 mg given for 14 d every 21 d, and 1 mg/m(2) of bortezomib initially given on days 1, 4, 8, and 11 for the first 20 cycles, and then weekly thereafter on days 1 and 8. Bortezomib was discontinued after 90 cycles, and the patient continued to receive lenalidomide monotherapy. As of cycle 100, the patient achieved a PR. Currently, she is clinically stable with response sustained for over 7 yrs. Therapy has been well tolerated with no significant long-term toxicity; no dose reductions of lenalidomide and bortezomib were required. The excellent tolerability of this steroid-free approach and the durable response seen underscore the potential benefits of participating in early phase clinical trials evaluating novel therapies and new drug combinations. This case further supports that combination treatment with lenalidomide and bortezomib is an effective therapy in the management of patients with relapsed and refractory MM. PMID- 22300349 TI - Reduction of graphene oxide by an in-situ photoelectrochemical method in a dye sensitized solar cell assembly. AB - Reduction of graphene oxide [GO] has been achieved by an in-situ photoelectrochemical method in a dye-sensitized solar cell [DSSC] assembly, in which the semiconductor behavior of the reduced graphene oxide [RGO] is controllable. GO and RGO were characterized by X-ray photoelectron spectroscopy, Raman spectroscopy, high-resolution transmission electron microscope, and Fourier transform infrared spectroscopy. It was found that the GO film, which assembled in the DSSC assembly as the counter electrode, was partly reduced. An optimized photoelectrochemical assembly is promising for modulating the reduction degree of RGO and controlling the band structure of the resulting RGO. Moreover, this method appeared to be a green progress for the production of RGO electrodes. PMID- 22300350 TI - Does it matter where we measure blood pressure? AB - Although blood pressure measured at the brachial artery plays a central role in our understanding and management of cardiovascular risk, in recent years great emphasis has been placed on the importance of central blood pressure. It seems straightforward that knowledge of the blood pressure directly affecting the major organs is important for understanding the pathophysiology and treatment of cardiovascular risk. However, the field has been troubled by controversies over measurement techniques and difficulty in designing therapies to modify central but not peripheral blood pressure. In this review, we consider the physiology underlying the change in blood pressure through the arterial tree and how central blood pressure can be measured. In addition, we review the evidence regarding the relationship of central BP to cardiovascular disease and the effects of treatment. New measurement techniques and evidence regarding the specific benefits of therapies in modulating central haemodynamics mean that this is a rapidly developing area, and understanding the concept of central blood pressure will be vital in the future. PMID- 22300351 TI - Topical treatment of cutaneous Kaposi sarcoma with imiquimod 5% in renal transplant recipients: a clinicopathological observation. AB - Kaposi sarcoma (KS) is a vascular neoplasm pathogenetically linked to human herpesvirus 8. Transplant recipients, in particular renal-transplant recipients (RTRs) are at higher risk for post-transplant (P)-KS which affects 0.2-11% of RTRs. The course of P-KS is influenced by the post-transplantation immunosuppressive treatment. Reduction of immunosuppressive drugs can result in tumour regression, and is the treatment of choice for P-KS, but is associated with the risk for transplant rejection. Imiquimod is a topically applied immunomodulator without relevant systemic absorption, and may thus represent a promising treatment for cutaneous KS in RTRs. The aim of this study was to investigate the clinical and histological effects of imiquimod in two RTRs with cutaneous KS. Imiquimod resulted in complete clinical and histologically proven remission in one patient, but in the second patient, although there was clinical remission, histological persistence of KS was found. Imiquimod may represent an effective treatment for RTRs with cutaneous P-KS. However, clinical remission does not necessarily indicate complete tumour regression, as shown in one of our patients, who had a persisting tumour, as shown by biopsy examination. Thus, histological confirmation is crucial to confirm complete response. PMID- 22300352 TI - Childhood blastic plasmacytoid dendritic cell neoplasm treated with allogenic stem cell transplantation. AB - Blastic plasmacytoid dendritic cell neoplasm is an uncommon malignancy with a high incidence of cutaneous involvement, risk of leukemic dissemination, and poor prognosis. We report a 15-year-old boy with blastic plasmacytoid dendritic cell neoplasm who was treated with acute myeloid leukemia-based polychemotherapy and subsequent allogenic stem cell transplantation. PMID- 22300353 TI - Syntheses and structures of Sc2Nb(4-x)Sn5, YNb6Sn6, and ErNb6Sn5: exploratory studies in ternary rare-earth niobium stannides. AB - Three new rare-earth (RE) niobium stannides, namely, Sc(2)Nb(4-x)Sn(5) (x = 0.37, 0.52), YNb(6)Sn(6), and ErNb(6)Sn(5), have been obtained by reacting the mixture of corresponding pure elements at high temperature and structurally characterized by single-crystal X-ray diffraction studies. Sc(2)Nb(4-x)Sn(5) crystallizes in the orthorhombic space group Ibam (No. 72) and belongs to the V(6)Si(5) type. Its structure features a three-dimensional (3D) network composed of two-dimensionally (2D) corrugated [Nb(2)Sn(2)] and [Nb(2)Sn(3)] layers interconnected via Nb-Sn bonds, forming one type of one-dimensional (1D) narrow tunnels along the c axis occupied by Sc atoms. YNb(6)Sn(6) crystallizes in the hexagonal space group P6/mmm (No. 191) and adopts the HfFe(6)Ge(6) type, and ErNb(6)Sn(5) crystallizes in the trigonal space group R3m (No. 166) and belongs to the LiFe(6)Ge(5) type. Their structures both feature 3D networks based on 2D [Nb(3)Sn], [Sn(2)], and [RESn(2)] layers (RE = Y, Er). In YNb(6)Sn(6), one type of [Nb(3)Sn] layer is interconnected by [Sn(2)] and [YSn(2)] layers via Nb-Sn bonds to form a 3D network. However, in ErNb(6)Sn(5), two types of [Nb(3)Sn] layers are interlinked by [Sn(2)] and [ErSn(2)] layers via Nb-Sn bonds into a 3D framework. Electronic structure calculations and magnetic property measurements for "Sc(2)Nb(4)Sn(5)" and YNb(6)Sn(6) indicate that both compounds show semimetallic and temperature independent diamagnetic behavior. PMID- 22300354 TI - Orientation of a dispersion of kaolinite flowing in a jet. AB - Orientational alignment in a dilute dispersion of kaolinite particles has been investigated in a flow pattern that combines both shear and elongational stress, namely flow at a jet created by a 2 mm diameter nozzle inserted in a 6 mm diameter pipe. Spatially-resolved X-ray diffraction with synchrotron radiation permits detailed maps of the alignment to be deduced and compared with fluid mechanics calculations of the flow. The angular distribution of diffracted intensity from a given position in the pipe provides information about the orientation distribution of the particles. This is quantified and presented in terms of order parameters. The cone-shaped nozzle provides a jet of liquid giving a high degree of alignment of the particles that is uniform along lines across the conical section and constant in the small straight-sided region at the exit of the nozzle. The vortex motion that arises from the flow with a modest Reynolds number could be determined as well as the tendency for some particles to align with their large faces perpendicular to the overall flow direction at the flat surface of the nozzle outlet. PMID- 22300355 TI - Double stapled haemorrhoidopexy for haemorrhoidal prolapse: indications, feasibility and safety. AB - AIM: Selected patients with haemorrhoidal prolapse undergoing double stapled anopexy with the procedure for prolapse and haemorrhoids (PPH03) were studied. METHOD: Between March 2007 and March 2010, 235 patients referred with haemorrhoids were included in the study. Patients with obstructed defaecation were excluded. At surgery intraoperative evaluation for double stapled anopexy was carried out based on the criteria of prolapse occupying half or more of the anal circumference and redundant prolapsed tissue determined by the circular anal dilator. Patients fulfilling these criteria were submitted for double stapled anopexy with the PPH03 stapler. All clinical and operative data were recorded in a prospectively maintained database. RESULTS: Among the 142 patients with haemorrhoidal prolapse having surgery 91 had a single and 51 a double stapled technique. The mean operative time was 34.8 min with no major or minor intraoperative complications. Recurrence at 48 months was 1.9% and the mean satisfaction score was 8.9. CONCLUSION: The double stapled PPH03 technique in selected cases was as safe and effective as a single stapling technique with a lower incidence of recurrence over a medium-term follow-up. PMID- 22300356 TI - Influence of alexithymia on health-related quality of life in inflammatory bowel disease: are there any related factors? AB - OBJECTIVE: Alexithymia is a personality trait characterized by difficulty to perceive and express emotions. Previous studies have indicated a high prevalence of alexithymia in patients with inflammatory bowel disease (IBD) but results have been inconsistent. The aim of the present study was to investigate the prevalence of alexithymia in a large IBD cohort and to establish the impact of alexithymia on health-related quality of life (HRQOL) in these patients. MATERIAL AND METHODS: A cross-sectional prospective study was undertaken including 534 consecutive IBD patients. Independent variables were measured using one socio demographic and clinical questionnaire, the hospital anxiety and depression scale (HADS) and the Toronto alexithymia scale (TAS-26). Dependent variables were measured using the short form 36 health survey (SF-36) and the inflammatory bowel disease questionnaire (IBDQ-36). Multiple linear regression and logistic regression were performed to identify factors associated with HRQOL. RESULTS: Participation rate was 91.3%. The overall prevalence of alexithymia was 30.2% (95% CI: 26.0-35.0), with no difference between Crohn's disease and ulcerative colitis. The most affected scales in quality of life were general health (mean = 48.35, 95% CI: 46.43-50.27), vitality (mean = 55.81, 95% CI: 53.59-58.04) and systemic symptoms (mean = 5.19, 95% CI: 5.08-5.29). Alexithymia was significantly associated with an impaired quality of life (OR = 3.34, 95% CI: 1.98-5.65). "Difficulty identifying feelings" and "externally oriented thinking" were the alexithymia factors related to the impaired HRQOL. CONCLUSIONS: Alexithymia is highly prevalent in IBD and represents a significant determinant of HRQOL. Alexithymia and its components need to be taken into consideration in the management of IBD patients. PMID- 22300357 TI - Validation of a new mixing chamber system for breath-by-breath indirect calorimetry. AB - Limited validation research exists for applications of breath-by-breath systems of expired gas analysis indirect calorimetry (EGAIC) during exercise. We developed improved hardware and software for breath-by-breath indirect calorimetry (NEW) and validated this system as well as a commercial system (COM) against 2 methods: (i) mechanical ventilation with known calibration gas, and (ii) human subjects testing for 5 min each at rest and cycle ergometer exercise at 100 and 175 W. Mechanical calibration consisted of medical grade and certified calibration gas ((4.95% CO(2), 12.01% O(2), balance N(2)), room air (20.95% O(2), 0.03% CO(2), balance N(2)), and 100% nitrogen), and an air flow turbine calibrated with a 3-L calibration syringe. Ventilation was mimicked manually using complete 3-L calibration syringe manouvers at a rate of 10.min(-1) from a Douglas bag reservoir of calibration gas. The testing of human subjects was completed in a counterbalanced sequence based on 5 repeated tests of all conditions for a single subject. Rest periods of 5 and 10 min followed the 100 and 175 W conditions, respectively. COM and NEW had similar accuracy when tested with known ventilation and gas fractions. However, during human subjects testing COM significantly under-measured carbon dioxide gas fractions, over-measured oxygen gas fractions and minute ventilation, and resulted in errors to each of oxygen uptake, carbon dioxide output, and respiratory exchange ratio. These discrepant findings reveal that controlled ventilation and gas fractions are insufficient to validate breath-by-breath, and perhaps even time-averaged, systems of EGAIC. The errors of the COM system reveal the need for concern over the validity of commercial systems of EGAIC. PMID- 22300358 TI - Impaired superficial femoral artery vasodilation and leg blood flow in young obese women following an oral glucose tolerance test. AB - This study was designed to test the hypothesis that glucose ingestion following an overnight fast increases leg vascular conductance (LVCd) and superficial femoral artery (SFA) vasodilation in lean but not obese young women. Obese (23.5 +/- 4.0 years, 84.7 +/- 14.7 kg, 37.2% +/- 6.4% fat; mean +/- SD, n = 8) and lean (23.8 +/- 2.4 years, 60.6 +/- 4.0 kg, 22.3% +/- 2.8% fat; n = 8) women arrived in the laboratory at 0830 h after a 12-h overnight fast for body composition (densitometry) assessment. Then, capillary blood glucose (BGlu), plasma insulin, heart rate, cardiac output, mean arterial pressure, leg blood flow (Doppler ultrasound), and LVCd were measured (after 15 min in the supine position), and at 30-min intervals for 2 h following glucose ingestion (75 g glucose load, 12.5% solution). Fasting BGlu concentration was not different between groups (obese = 5.1 +/- 0.47 vs. lean = 4.9 +/- 0.37 mmol.L(-1), p = 0.71) but 60, 90, and 120 min post ingestion BGlu was elevated (p <= 0.03) in the obese women. Insulin differences were not significant. Fasting LVCd was not different between groups (lean = 0.72 +/- 0.49 vs. obese = 0.70 +/- 0.19 mL.min(-1).mm Hg(-1); p = 0.48); however, LVCd, as well as Delta in SFA diameter were significantly elevated (p <= 0.04) in the lean compared with the obese group at 60, 90, and 120 min postglucose ingestion (LVCd, peak lean = 1.4 +/- 0.5 vs. peak obese = 0.8 +/- 0.1 mL.min(-1).mm Hg(-1); Delta in SFA, peak lean = 0.51 +/- 0.30 vs. peak obese = 0.09 +/- 0.45 mm). The reduced LVCd following glucose ingestion could contribute to impaired glucose tolerance. Further, the lack of SFA dilation may be evidence of impaired vascular insulin responsiveness in these obese young women. PMID- 22300359 TI - Combined effects of aerobic exercise and high-carbohydrate meal on plasma acylated ghrelin and levels of hunger. AB - The present study investigated the effect of an aerobic exercise bout associated with a high-carbohydrate (CHO) meal on plasma levels of acylated ghrelin and hunger sensation. Eight healthy males performed an exercise (ET) and a control (CT) trial. In ET, participants performed a 60-min cycling exercise (~70% of maximal oxygen uptake) after consuming a high-CHO meal. In the CT, participants remained at rest throughout the whole period after consuming the high-CHO meal. Hunger sensation was assessed and blood samples were taken to determine the levels of acylated ghrelin, glucose, insulin, total cholesterol (TC), and triglycerides (TG). There was suppression of hunger after consuming the meal in ET and CT (p = 0.028 and p = 0.011, respectively). Hunger increased in CT in the period correspondent to the exercise session (p = 0.017) and remained suppressed in the ET. The area under the curve for acylated ghrelin showed that its levels were lower in the ET compared with CT in the period of the exercise plus the immediate period (1 h) postexercise (60.7 vs. 96.75 pg.mL(-1).2 h(-1), respectively; p = 0.04). Inverse correlations between acylated ghrelin levels and insulin, TC, and TG levels at different time points were observed. In conclusion, these findings suggest that 1 bout of aerobic exercise maintains the meal-induced suppression of hunger. The mechanism underlying this effect may involve the exercise-induced suppression of acylated ghrelin. These results implicate that the combination of a high-CHO meal and aerobic exercise may effectively improve appetite control and body weight management. PMID- 22300361 TI - Circadian type and mood seasonality in adolescents. AB - The aim of the present study was to investigate, for the first time, the relationship between circadian preference and mood seasonality in adolescents. To this end, 1539 participants (881 female; 658 male) completed the Morningness Eveningness Questionnaire for Children and Adolescents and the Seasonal Pattern Assessment Questionnaire for Children and Adolescents to determine circadian preference and mood seasonality, respectively. Evening types achieved significantly higher mood seasonality scores than intermediate and morning types, as intermediates did than morning types. Agreeing with previous studies on young adults and adults, the present data indicate a significant relationship between eveningness and higher mood seasonality in adolescents. PMID- 22300362 TI - Long-term outcomes of phacoemulsification cataract surgery performed by trainees and consultants in an Australian cohort. AB - BACKGROUND: It is unclear whether differences exist in surgical complication rates and long-term visual acuity outcomes between patients whose phacoemulsification cataract surgery was performed by ophthalmological trainees and those performed by consultants. DESIGN: Prospective clinical cohort study. PARTICIPANTS: 1851 participants of the Cataract Surgery and Age-related Macular Degeneration study, aged >=64 years, had cataract surgery performed at Westmead Hospital, Sydney. METHODS: Surgical complication rates and visual acuity at 24 month postoperative visits were compared between patients who were operated on by trainees and those operated on by consultants. MAIN OUTCOME MEASURES: Surgical outcomes included operative complications recorded in surgical audit forms and 24 month postoperative visual acuity. RESULTS: Of 1851 patients, 1274 (68.8%) were reviewed 24 months after surgery. Of these, 976 had data on the type of surgeon who performed the operation. After excluding 152 challenging cases and three cases operated on by first-year trainees at the beginning of their training, 821 patients were included in this study, of those, 498 were operated on by trainees and 323 by consultants. Habitual visual acuity >=6/12 was achieved in 77.3% (n = 385/498) and 74.3% (n = 240/323), respectively, of the two groups of patients 24 months postoperatively. Of 514 patients who had surgical audit data, the major complication rate was numerically greater, but not significantly different for the 330 trainee-operated (6.1%) patients, compared with the 184 consultant operated patients (2.7%, P = 0.091). CONCLUSIONS: We found relatively comparable complication rates and visual outcomes after 2 years between patients operated on by ophthalmological trainees and those by consultants, in a cataract surgical cohort at Westmead Hospital. PMID- 22300364 TI - Replicative aging and differentiation potential of human adipose tissue-derived mesenchymal stromal cells expanded in pooled human or fetal bovine serum. AB - BACKGROUND AIMS: Mesenchymal stromal cells (MSC) are promising candidates for innovative cell therapeutic applications. For clinical-scale manufacturing, different supplements have been evaluated as alternatives for the commonly used fetal bovine serum (FBS). We have reported previously that pooled human AB serum (HS) accelerates the proliferation of adipose tissue-derived MSC (ASC) while maintaining key functions of MSC biology such as differentiation, immune suppression and growth factor secretion. ASC expanded in FBS-supplemented culture media undergo replicative aging that is associated with a progressive loss of differentiation capacity but without indications of cellular transformation. The effects of HS media on ASC long-term culture, however, remain poorly characterized. METHODS: Long-term cultures of ASC in FBS and HS media were analyzed with respect to proliferation, marker expression, differentiation and immune suppression. RESULTS: Despite signs of an accelerated proliferation, extended life span and clonogenic capacity of ASC cultivated in HS-supplemented media, HS and FBS cultures revealed no significant differences with respect to differentiation potential and expression of senescence markers. Anchorage independent growth, which is indicative of tumorigenic properties, was not observed in either culture conditions. Similarly, immune suppressive activities were maintained. Donor variation regarding differentiation potential and marker expression became apparent in this study independent of the culture supplement or culture duration. CONCLUSIONS: We have demonstrated that the use of pooled allogeneic HS maintains the characteristics of ASC even after long-term expansion, further demonstrating that the use of HS is an alternative to FBS. PMID- 22300365 TI - An unusual subcutaneous lump. PMID- 22300366 TI - The World Journal of Biological Psychiatry. Editorial. PMID- 22300368 TI - Application of 204mPb perturbed angular correlation of gamma-rays spectroscopy in coordination chemistry. AB - (204m)Pb perturbed angular correlation of gamma-rays (PAC) spectroscopy has been applied successfully for the first time to detect the nuclear quadrupole interaction in a lead(II) coordination compound in a molecular crystal [tetraphenylarsonium lead(II) isomaleonitriledithiolate ([AsPh(4)](4)[Pb(2)(i mnt)(4)])]. The recorded parameters from a powder crystalline sample are nu(Q) = 0.178(1) GHz and eta = 0.970(7). The electric field gradient (EFG) was determined at the PW91/QZ4P level including relativistic effects using the two-component zeroth-order regular approximation method for both the [Pb(i-mnt)(2)](2-) monomer and the [Pb(2)(i-mnt)(4)](4-) dimer. Only the EFG for the latter compares favorably with the experimental data, indicating that the picture of this complex as a prototypical hemidirected coordination geometry with a stereochemically active lone pair on lead(II) is inadequate. Advantages and limitations of (204m)Pb PAC spectroscopy as a novel technique to elucidate the electronic and molecular structures of lead-containing complexes and biomolecules are presented. PMID- 22300367 TI - Pharmacokinetic interaction study of sulphasalazine in healthy subjects and the impact of curcumin as an in vivo inhibitor of BCRP. AB - BACKGROUND AND PURPOSE An ATP-binding cassette (ABC) transporter, breast cancer resistance protein (BCRP)/ABCG2, limits oral bioavailability of sulphasalazine. Here we examined the effect of curcumin, the principal curcuminoid of turmeric, on oral bioavailability of microdoses and therapeutic doses of sulphasalazine in humans. EXPERIMENTAL APPROACH Effects of curcumin were measured on the ATP dependent sulphasalazine uptake by hBCRP-expressing membrane vesicles and on oral bioavailability of sulphasalazine in wild-type and Bcrp(-/-) mice. Eight healthy Japanese subjects received an oral dose of sulphasalazine suspension (100 ug) or tablets (2 g) alone or after curcumin tablets (2 g). Uptake of sulphasalazine was studied in HEK293 cells transfected with the influx transporter (OATP)2B1. KEY RESULTS Curcumin was a potent hBCRP inhibitor in vitro (K(i) 0.70 +/- 0.41 uM). Curcumin increased the area under the curve (AUC)(0-8) of plasma sulphasalazine eightfold in wild-type mice at 300 and 400 mg.kg(-1), but not in Bcrp(-/-) mice. Curcumin increased AUC(0-24) of plasma sulphasalazine 2.0-fold at microdoses and 3.2-fold at therapeutic doses in humans. Non-linearity of the dose-exposure relationship was observed between microdoses and therapeutic doses of sulphasalazine. Sulphasalazine was a substrate for OATP2B1 (K(m) 1.7 +/- 0.3 uM). Its linear index (dose/K(m)) at the therapeutic dose was high and may saturate OATP2B1. CONCLUSIONS AND IMPLICATIONS Curcumin can be used to investigate effects of BCRP on oral bioavailability of drugs in humans. Besides the limited dissolution, OATP2B1 saturation is a possible mechanism underlying non-linearity in the dose-exposure relationship of sulphasalazine. PMID- 22300369 TI - A novel nonsense mutation in RSPO4 gene underlies autosomal recessive congenital anonychia in a Pakistani family. AB - Congenital anonychia is an inherited autosomal recessive disorder characterized by complete absence of fingernails or toenails, or both. In the present study, we have described a consanguineous Pakistani family having a family member affected with congenital anonychia. Genotyping using polymorphic microsatellite markers showed linkage of the family to gene RSPO4 encoding R-spondin and mapped on human chromosome 20p13. Deoxyribonucleic acid sequence analysis of the gene identified a novel nonsense mutation (c.18C>A; p.Cys6X) in the affected family member. PMID- 22300371 TI - Role of lentivirus-mediated overexpression of programmed death-ligand 1 on corneal allograft survival. AB - To investigate the role of lentivirus-mediated overexpression of programmed death ligand 1 (PD-L1) on rat corneal allograft survival. A fully allogeneic rat cornea transplant model was used for in vivo studies. Lentiviral (LV) vectors are efficient tools for ex vivo genetic modification of cultured corneas. LV vector encoding for PD-L1 (LV.PD-L1) and LV vector encoding for eGFP (LV.eGFP, as control) were constructed and tested. PD-L1 or eGFP expression was increased on corneal cells upon LV.PD-L1 and LV.eGFP transduction, respectively. Both allogeneic controls and allogeneic LV.eGFP transduced corneas were uniformly rejected (MST: 13.8 +/- 1.7 days and 12.3 +/- 1.9 days, respectively). In contrast, allogeneic LV.PD-L1 transduced corneas showed a high percentage (83%) of graft survival (MST > 30 days, n = 5, 15 days, n = 1). Graft opacity of PD-L1 transduced corneas was present but was significantly reduced compared to control or eGFP expressing corneas. Flow cytometric analysis revealed that percentages of CD3(+) CD8(+) CD161(+) and CD3(+) CD8(+) CD161(-) lymphocytes were decreased in animals receiving LV.PD-L1 transduced corneas compared to animals grafted with LV.eGFP transduced corneas. Moreover, reduced expression of proinflammatory cytokines (IFN-gamma and IL-6) in PD-L1 transduced corneas compared to allogeneic controls was also observed. Local PD-L1 gene transfer in cultured corneas is a promising approach for the prolongation of corneal allograft survival and attenuation of graft rejection. PMID- 22300372 TI - A long-term follow-up of allergic diseases in Iceland. AB - INTRODUCTION: Allergic disorders are an increasing health problem in many countries, in particular among children. We have evaluated the prevalence and manifestations of allergy in a cohort of young Icelanders for more than two decades. Variations in the epidemiology and clinical expression of allergy in different communities may help to identify etiological factors contributing to these disorders. METHODS: A cohort of 179 children has been monitored for allergic manifestations for two decades, at the ages of two, four, eight, and 15 years, and most recently at the age of 21 years involving 120 of the participants. RESULTS: Cumulative prevalences of 40%, 45%, and 29% have been observed, respectively, for rhinoconjunctivitis, eczema, and asthma during the study period. None had developed rhinoconjunctivitis at the age of about 2 years, but the point prevalence gradually increased to 33% at the age of 21 years. Conversely, the prevalence of eczema was 31% at the age of 2 years, but gradually declined to 8% at the age of 21 years. The prevalence of asthma peaked at 28% at the age of 4 years, but declined thereafter and has remained stable at about 13% from the age of eight to 21 years. DISCUSSION: The prevalence of allergic diseases is high in Iceland among children and young individuals. Asthma and atopic eczema are very common in childhood, but decreases with age while the prevalence of rhinoconjunctivitis increases markedly. The very high and increasing prevalence of rhinoconjunctivitis among 15- to 21-year-old individuals is noteworthy. PMID- 22300373 TI - Formation of nanometer-sized surface platinum oxide clusters on a stepped Pt(557) single crystal surface induced by oxygen: a high-pressure STM and ambient pressure XPS study. AB - We studied the oxygen-induced restructuring process on a stepped Pt(557) single crystal surface using high-pressure scanning tunneling microscopy (HP-STM) and ambient-pressure X-ray photoelectron spectroscopy (AP-XPS) at O(2) pressures up to 1 Torr. HP-STM has revealed that nanometer-sized clusters are created on Pt(557) at 1 Torr of O(2) and at room temperature. These clusters are identified as surface Pt oxide by AP-XPS. The appearance of clusters is preceded by the formation of 1D chain structures at the step edges. By using a Pt(111) surface as a reference, it was found that the step sites are the nucleation centers for the formation of surface oxide clusters. These surface oxide clusters disappear and the stepped structure is restored on Pt(557) after evacuating O(2) to 10(-8) Torr. Changes in the surface oxide concentration in response to variations in the O(2) gas pressure are repeatable for several cycles. Our results that small clusters are initiated at step sites at high pressures demonstrate the importance of performing in situ characterization of stepped Pt catalysts under reaction conditions. PMID- 22300374 TI - Educating nonmedical prescribers. AB - The last decade has seen developments in nonmedical prescribing, with the introduction of prescribing rights for healthcare professionals. In this article, we focus on the education, training and practice of nonmedical prescribers in the UK. There are around 20,000 nurse independent prescribers, 2400 pharmacist supplementary/independent prescribers, several hundred allied health professional supplementary prescribers and almost 100 optometrist supplementary/independent prescribers. Many are active prescribers, managing chronic conditions or acute episodes of infections and minor ailments. Key aims of nonmedical prescribing are as follows: to improve patient care; to increase patient choice in accessing medicines; and to make better use of the skills of health professionals. Education and training are provided by higher education institutions accredited by UK professional bodies/regulators,namely, the Nursing and Midwifery Council, General Pharmaceutical Council, Health Professions Council and General Optical Council. The programme comprises two main components: a university component equivalent to 26 days full-time education and a period of learning in practice of 12 days minimum under the supervision of a designated medical practitioner. Course content focuses on the following factors: consultation, decision making, assessment and review; psychology of prescribing; prescribing in team context; applied therapeutics; evidence-based practice and clinical governance; legal, policy, professional and ethical aspects; and prescribing in the public health context. Nonmedical prescribers must practise within their competence, demonstrating continuing professional development to maintain the quality engendered during training. Despite the substantial progress, there are several issues of strategy, capacity, sustainability and a research evidence base which require attention to fully integrate nonmedical prescribing within healthcare. PMID- 22300375 TI - Growth of few-wall carbon nanotubes with narrow diameter distribution over Fe-Mo MgO catalyst by methane/acetylene catalytic decomposition. AB - Few-wall carbon nanotubes were synthesized by methane/acetylene decomposition over bimetallic Fe-Mo catalyst with MgO (1:8:40) support at the temperature of 900 degrees C. No calcinations and reduction pretreatments were applied to the catalytic powder. The transmission electron microscopy investigation showed that the synthesized carbon nanotubes [CNTs] have high purity and narrow diameter distribution. Raman spectrum showed that the ratio of G to D band line intensities of IG/ID is approximately 10, and the peaks in the low frequency range were attributed to the radial breathing mode corresponding to the nanotubes of small diameters. Thermogravimetric analysis data indicated no amorphous carbon phases. Experiments conducted at higher gas pressures showed the increase of CNT yield up to 83%. Mossbauer spectroscopy, magnetization measurements, X-ray diffraction, high-resolution transmission electron microscopy, and electron diffraction were employed to evaluate the nature of catalyst particles. PMID- 22300376 TI - Oxidation of the antiviral drug acyclovir and its biodegradation product carboxy acyclovir with ozone: kinetics and identification of oxidation products. AB - The oxidation of the antiviral drug acyclovir (ACV) and its main biotransformation product carboxy-acyclovir (carboxy-ACV) by ozone was investigated. Both compounds have recently been detected in surface water, and carboxy-ACV has also been detected in drinking water. The experiments revealed a strong pH dependence of the oxidation of ACV and carboxy-ACV with reaction rate constants increasing by 4 orders of magnitude between the protonated, positively charged form (k(ox,PH(+)), ~2.5 * 10(2) M(-1) s(-1)) and the deprotonated, negatively charged form (k(ox,P(-)), 3.4 * 10(6) M(-1) s(-1)). At pH 8 a single oxidation product was formed which was identified via LC-LTQ-Orbitrap MS and NMR as N-(4-carbamoyl-2-imino-5-oxoimidazolidin)formamido-N-methoxyacetic acid (COFA). Using Vibrio fischeri , an acute bacterial toxicity was found for COFA while carboxy-ACV revealed no toxic effects. Ozonation experiments with guanine and guanosine at pH 8 led to the formation of the respective 2-imino-5 oxoimidazolidines, confirming that guanine derivatives such as carboxy-ACV are undergoing the same reactions during ozonation. Furthermore, COFA was detected in finished drinking water of a German waterworks after ozonation and subsequent activated carbon treatment. PMID- 22300377 TI - Microbial chemical signaling: a current perspective. AB - Communication among microorganisms is mediated through quorum sensing. The latter is defined as cell-density linked, coordinated gene expression in microbial populations as a response to threshold signal concentrations followed by induction of a synchronized population response. This phenomenon is used by a variety of microbes to optimize their survival in a constantly challenging, dynamic milieu, by correlating individual cellular functions to community-based requirements. The synthesis, secretion, and perception of quorum-sensing molecules and their target response play a pivotal role in quorum sensing and are tightly controlled by complex, multilayered and interconnected signal transduction pathways that regulate diverse cellular functions. Quorum sensing exemplifies interactive social behavior innate to the microbial world that controls features such as, virulence, biofilm maturation, antibiotic resistance, swarming motility, and conjugal plasmid transfer. Over the past two decades, studies have been performed to rationalize bacterial cell-to-cell communication mediated by structurally and functionally diverse small molecules. This review describes the theoretical aspects of cellular and quorum-sensing mechanisms that affect microbial physiology and pathobiology. PMID- 22300378 TI - Transhilar passage in right graft live donor liver transplantation: intrahilar anatomy and its impact on operative strategy. AB - The passage through the hilar plate during right graft live donor liver transplantation (LDLT) can have dangerous consequences for both donors and recipients. The purpose of our study was to delineate hilar transection and biliary reconstruction strategies in right graft LDLT, with special consideration of central and peripheral hilar anatomical variants. A total of 71 consecutive donors underwent preoperative three-dimensional (3D) CT reconstructions and virtual 3D hepatectomies. A three-modal hilar passage strategy was applied, and its impact on operative strategy analyzed. In 68.4% of cases, type I and II anatomical configurations allowed for an en block hilar transection with simple anastomotic reconstructions. In 23.6% of cases, donors had "difficult" type II and types III/IV hilar bile duct anatomy that required stepwise hilar transections and complex graft biliary reconstructions. Morbidity rates for our early (A) and recent (B) experience periods were 67% and 39%, respectively. (1) Our two-level classification and 3D imaging technique allowed for donor individualized transhilar passage. (2) A stepwise transhilar passage was favored in types III and IV inside the right-sided hilar corridor. (3) Reconstruction techniques showed no ameliorating effect on early/late biliary morbidity rates. PMID- 22300379 TI - Molecularly imprinted aptamers of gold nanoparticles for the enzymatic inhibition and detection of thrombin. AB - We prepared thrombin-binding aptamer-conjugated gold nanoparticles (TBA-Au NPs) through a molecularly imprinted (MP) approach, which provide highly efficient inhibition activity toward the polymerization of fibrinogen. Au NPs (diameter, 13 nm), 15-mer thrombin-binding aptamer (TBA(15)) with different thymidine linkers, and 29-mer thrombin-binding aptamer (TBA(29)) with different thymidine linkers (Tn) in the presence of thrombin (Thr) as a template were used to prepare MP-Thr TBA(15)/TBA(29)-Tn-Au NPs. Thrombin molecules were then removed from Au NPs surfaces by treating with 100 mM Tris-NaOH (pH ca. 13.0) to form MP TBA(15)/TBA(29)-Tn-Au NPs. The length of the thymidine linkers and TBA density on Au NPs surfaces have strong impact on the orientation, flexibility, and stability of MP-TBA(15)/TBA(29)-Tn-Au NPs, leading to their stronger binding strength with thrombin. MP-TBA(15)/TBA(29)-T(15)-Au NPs (ca. 42 TBA(15) and 42 TBA(29) molecules per Au NP; 15-mer thymidine on aptamer terminal) provided the highest binding affinity toward thrombin with a dissociation constant of 5.2 * 10(-11) M. As a result, they had 8 times higher anticoagulant (inhibitory) potency relative to TBA(15)/TBA(29)-T(15)-Au NPs (prepared in the absence of thrombin). We further conducted thrombin clotting time (TCT) measurements in plasma samples and found that MP-TBA(15)/TBA(29)-T(15)-Au NPs had greater anticoagulation activity relative to four commercial drugs (heparin, argatroban, hirudin, and warfarin). In addition, we demonstrated that thrombin induced the formation of aggregates from MP-TBA(15)-T(15)-Au NPs and MP-TBA(29)-T(15)-Au NPs, thereby allowing the colorimetric detection of thrombin at the nanomolar level in serum samples. Our result demonstrates that our simple molecularly imprinted approach can be applied for preparing various functional nanomaterials to control enzyme activity and targeting important proteins. PMID- 22300381 TI - Whole genome microarray of the major pelvic ganglion after cavernous nerve injury: new insights into molecular profile changes after nerve injury. AB - What's known on the subject? and What does the study add? With the present study, we aimed to provide a global picture of the molecular processes that are activated by CN injury. The present study used genomic expression profiling to identify candidate genes that might be useful targets in the CN recovery process and, thus, the ultimate preservation of penile erection. Regeneration of the CN and axonal outgrowth clearly involve changes in multiple biochemical pathways that have never been investigated by microarray analysis. We analyzed global gene expression in the major pelvic ganglion at early stages (48 h and 14 days) after CN injury and focused on the detection of changes in genes related to nervous tissue repair and proliferation. The findings of the present study provide important insight into the molecular systems affected by CN injury and identify candidate genes that may be utilized for novel molecular-based therapies for the preservation and protection of the CN during RP. OBJECTIVES: To to examine the complexity of the many molecular systems involved in supporting cavernous nerve (CN) repair and regeneration in a rat model of bilateral crush injury utilizing a microarray analysis approach. Erectile dysfunction (ED) is a common clinical complication after prostate cancer treatment by radical prostatectomy, and recovery of erectile function can take as long as 2 years. There are gaps in our understanding of the autonomic pelvic innervation of the penis that still need to be addressed for the development of an adequate treatment strategy for post prostatectomy ED. The molecular mechanisms of the intrinsic ability of CN to regenerate after an injury have not been elucidated. MATERIALS AND METHODS: We analyzed global gene expression in the major pelvic ganglion 48 h and 14 days after CN injury. Overall, a comparative analysis showed that 325 genes changed at the 48-h time point and 114 genes changed at 14 days. There were 60 changed genes in common with both time points. Using the Ingenuity Pathway Analysis(r) system (Ingenuity Systems, Inc., Redwood City, CA, USA), we were able to analyze the significantly changed genes that were unique and common to each time point by biological function. We focused on the detection of changes related to nervous tissue repair and proliferation, molecular networks of neurotrophic factors, stem cell regulation and synaptic transmission. RESULTS: There was strong evidence of the early mobilization of genes involved in repair and neuroprotection mechanisms (SERPINF1, IGF1, PLAU/PLAUR, ARG1). Genes related to nervous system development (ATF3 GJA1, PLAU, SERPINE1), nerve regeneration (SERPINE2, IGF1, ATF3, ARG1) and synaptic transmission (GJC1, GAL) were changed. Several genes related to proliferation as well as apoptosis (A2M, ATF3, C3, EGR4, FN1, GJA1, GAL) were also changed, possibly as part of a protective mechanism or the initiation of remodelling. CONCLUSIONS: The results obtained show that multiple biological processes are associated with injury and repair of the CN and provide a systematic genome-wide screen for neurotrophic and/or inhibitory pathways of nerve regeneration. These data identify the candidate genes that may be utilized in novel molecular-based therapies for the preservation and protection of the CN during radical prostatectomy. PMID- 22300385 TI - Abstracts of the 10th International Kawasaki Disease Symposium. February 7-10, 2012. Kyoto, Japan. PMID- 22300387 TI - A(3) adenosine receptor: a plausible therapeutic target for cardio-protection in diabetes. AB - Diabetes mellitus categorized as type I and II, is a disease of pancreatic insulin, affecting blood glucose level in the body. Recent evidence suggests that cardiac diseases such as hypertension, coronary artery disease, congestive heart failure, and diabetic cardiomyopathy are associated with diabetes and hyperglycemia. The adenosine receptors (AR) have been reported to play an important role in the regulation of these diseases. Four adenosine receptors have been cloned and characterized from several different mammalian species. The receptors are named adenosine A(1), A(2A), A(2B), and A(3). The A(2A) and A(2B) receptors preferably interact with members of the Gs family of G proteins and the A(1) and A(3) receptors with Gi/o proteins. The ubiquitous levels of adenosine are found in each cell in normal conditions but in disease conditions its level has been shown to increase and activate G-protein mediated signaling pathway leading to artery constriction in cardiovascular diseases and diabetes. Various studies have demonstrated that A(3)AR is a potent cardioprotectant during myocardial ischemeia/ischemic reperfusion. Role of A(3)AR receptor as a possible cardioprotectant in diabetes is under investigation and studies have verified the involvement of cyclooxygenases (COXs) and NADPH oxidase pathways. This review summarizes the possible role of A(3)AR in cardiovascular disease and discusses advancement in the development of therapeutic agents targeting cardioprotection with discussion on recent patents on A(3) agonists that are being utilized in the clinical setting. We anticipate that detailed pharmacological studies of adenosine A(3) receptors could help in understanding the link between cardiovascular disease and diabetes and this can be utilized to develop newer therapies that selectively target A(3) receptor to overcome cardiac challenges. PMID- 22300388 TI - Lens thickness and associated factors. AB - BACKGROUND: To determine the normative data for lens thickness and its associated factors in a population-based study. DESIGN: Population-based study. PARTICIPANTS: The Central India Eye and Medical Study included 4711 subjects (aged 30+ years). METHODS: The subjects underwent a detailed ophthalmological examination including measurement of the lens thickness by sonography. MAIN OUTCOME MEASURE: Sonographic lens thickness measurement. RESULTS: After excluding pseudophakic or aphakic eyes, lens thickness measurements were available for 9046 eyes of 4610 (97.9%) subjects with a mean age of 49.1 +/- 13.2 years (range: 30-100 years) and a mean refractive error of -0.11 +/- 1.77 dioptres (median, 0 dioptres; range, -21.75 to +7.75 dioptres). Mean lens thickness was 3.95 +/- 0.49 mm. In multivariate analysis, a thick lens was significantly associated with higher age (P < 0.001), male gender (P < 0.001), higher body stature (P = 0.02), higher body mass index (P = 0.003), thicker central cornea (P = 0.008), shallower anterior chamber depth (P < 0.001) and hyperopic refractive error (P < 0.001). After adjustment for ocular and systemic parameters, lens thickness decreased with higher degree of nuclear cataract. CONCLUSIONS: In the rural Central Indian population, a thick lens was associated with higher age, male gender, high body stature, high body mass index, hyperopia, thick central cornea, shallow anterior chamber depth and nuclear cataract. The data may be helpful to explain anatomic relationships of the anterior segment of the eye and to elucidate risk factors of diseases associated with ocular dimensions. PMID- 22300389 TI - Dual regulation by ethanol of the inhibitory effects of ketamine on spinal NMDA induced pressor responses in rats. AB - BACKGROUND: Acute exposure of ethanol (alcohol) inhibits NMDA receptor function. Our previous study showed that acute ethanol inhibited the pressor responses induced by NMDA applied intrathecally; however, prolonged ethanol exposure may increase the levels of phosphorylated NMDA receptor subunits leading to changes in ethanol inhibitory potency on NMDA-induced responses. The present study was carried out to examine whether acute ethanol exposure influences the effects of ketamine, a noncompetitive NMDA receptor antagonist, on spinal NMDA-induced pressor responses. METHODS: The blood pressure responses induced by intrathecal injection of NMDA were recorded in urethane-anesthetized rats weighing 250-275 g. The levels of several phosphorylated residues on NMDA receptor GluN1 subunits were determined by western blot analysis. RESULTS: Intravenous injection of ethanol or ketamine inhibited spinal NMDA-induced pressor responses in a dose dependent and reversible manner. Ketamine inhibition of NMDA-induced responses was synergistically potentiated by ethanol when ethanol was applied just before ketamine. However, ketamine inhibition was significantly reduced when applied at 10 min after ethanol administration. Western blot analysis showed that intravenous ethanol increased the levels of phosphoserine 897 on GluN1 subunits (pGluN1-serine 897), selectively phosphorylated by protein kinase A (PKA), in the lateral horn regions of spinal cord at 10 min after administration. Intrathecal administration of cAMPS-Sp, a PKA activator, at doses elevating the levels of pGluN1-serine 897, significantly blocked ketamine inhibition of spinal NMDA induced responses. CONCLUSIONS: The results suggest that ethanol may differentially regulate ketamine inhibition of spinal NMDA receptor function depending on ethanol exposure time and the resulting changes in the levels of pGluN1-serine 897. PMID- 22300390 TI - Real-time mapping of rat stomach lymph nodes by quantum dots. AB - OBJECTIVE: To develop a real-time imaging method to identify the rat stomach lymph node basin with quantum dots (Qdots). MATERIAL AND METHODS: Six Sprague Dawley rats received injections of 0.05 ml Qdots (1 mg/ml) in the subserosal layer in the lesser curvature of the gastric antrum. Subsequently, draining lymphatic channels and lymph nodes were visualized with a near-infrared fluorescence imaging system. Histological examination was required to confirm the presence of lymph nodes. Additionally, rats received injections of Qdots and underwent 2 weeks of observation to confirm if there was any abnormality. The distribution of Qdots was measured by inductively coupled plasma-mass spectrometry. RESULTS: After injection of the Qdots, the gastric sentinel lymph nodes were visualized 15 min later. The fluorescence then began to spread. The intensity of fluorescence increased in the perigastric area at 60 min, and declined at 360 min. Histological analysis of the fluorescent tissue confirmed the presence of nodal tissue. The results of a cadmium assay showed that Qdots were mainly distributed in the liver, spleen and kidney of the rats. No apparent toxicity could be seen during the 2 weeks of observation. CONCLUSIONS: NIR fluorescence imaging of lymph nodes with Qdots is a novel and reliable real-time technique that can be used to assist with identification and resection of stomach lymph nodes. The optimal observation time of perigastric SLNs was 15 min after the injection, and the optimal observation time of perigastric lymph nodes beyond the SLNs was 60-120 min after the injection. PMID- 22300391 TI - Lichen striatus successfully treated with photodynamic therapy. PMID- 22300392 TI - Characterization and evaluation of beta-glucan formulations as injectable implants for protein and peptide delivery. AB - CONTEXT: Injectable implants are biodegradable, syringeable formulations that are injected as liquids, but form a gel inside the body due to a change in pH, ions or temperature. OBJECTIVE: To investigate the effect of polymer concentration, pH, ions and temperature on the gel formation of beta-glucan, a natural cell-wall polysaccharide derived from barley, with particular emphasis on two-phase system formation after addition of dextran or PEG. MATERIALS AND METHODS: Oscillation viscometry was used to evaluate the gel character by measuring flow index (N), storage (G') and loss (G") moduli. Two-phase systems were further characterized for hardness and syringeability using a texture analyzer. Finally, in vitro release characteristics were determined using Franz diffusion cells. RESULTS: Oscillation viscometry revealed that only addition of dextran or PEG resulted in distinct gel formation. This was seen by a decrease in N after polymer addition. Moreover, hardness (in g) of the gels increased significantly (p < 0.001) from 3.65 +/- 0.43 to 34.30 +/- 8.90 (dextran) and 805.80 +/- 5.30 (PEG) 24 h after polymer addition. In vitro release profiles showed significantly (p < 0.05) reduced AUC(0-8 h), k and percentage of drug released from two-phase systems compared to beta-glucan dispersions, with the PEG system resulting in the lowest amount released over 8 h (15.1 +/- 1.6%). DISCUSSION: The unfavorable mixing enthalpy and higher water affinity of PEG resulted in the formation of a dense beta-glucan gel. CONCLUSION: 1.5% (w/w) beta-glucan combined with PEG at a ratio of 1:3 seemed to be the most promising injectable formulation with respect to fastest gel formation, increased hardness and sustained release. PMID- 22300393 TI - Stuve-Wiedemann syndrome and related bent bone dysplasias. AB - Stuve-Wiedemann syndrome (SWS) is a severe congenital skeletal dysplasia associated with life threatening dysautonomic manifestations. Newborns affected with this condition exhibit distinctive shortening and bowing of the long bones with reduced bone volume. The majority of affected newborns die early due to neuromuscular complications namely hyperthermia, apnea, and swallowing difficulties. In this review, we provide an overall picture on the clinical, including long-term management, molecular and cellular aspects of SWS and discuss briefly other related bent bone dysplasias. PMID- 22300394 TI - Pharmacokinetics of verapamil and its metabolite norverapamil in rats with hyperlipidaemia induced by poloxamer 407. AB - In this study, the pharmacokinetics of verapamil and its active metabolite norverapamil were evaluated following intravenous and oral administration of 10 mg/kg verapamil to rats with hyperlipidaemia (HL) induced by poloxamer 407 (HL rats). The total area under the plasma concentration time curve (AUC) of verapamil in HL rats following intravenous administration was significantly greater (by 11.2%) than in control rats due to their slower (by 11%) non-renal clearance. The oral AUC of verapamil in HL rats was also significantly greater (by 116%) compared with controls, with a larger magnitude than the data observed following intravenous administration. This may have been a result of the decreased intestinal metabolism of verapamil in HL rats. The AUC of norverapamil and AUC(norverapamil)/AUC(verapamil) ratios following intravenous and oral administration of verapamil were unchanged in HL rats. Assuming that the HL rat model qualitatively reflects similar changes in patients with HL, the findings of this study have potential therapeutic implications. Further studies in humans are required to determine whether modification of the oral verapamil dosage regimen in HL states is necessary. PMID- 22300395 TI - Allergic contact dermatitis to Pampers Drymax. AB - We present four cases of children less than 2 years of age, seen in four different practices, with a similar, unique, and specific presentation of diaper dermatitis, all while using Pampers Baby Dry with Drymax technology. To date, no reported cases exist of allergic contact dermatitis to Pampers Dryweave in medical literature. PMID- 22300397 TI - Virtual screening and evaluation of Ketol-Acid Reducto-Isomerase (KARI) as a putative drug target for Aspergillosis. AB - Aspergillus is a leading causative agent for fungal morbidity and mortality in immuno-compromised patients. To identify a putative target to design or identify new antifungal drug, against Aspergillus is required. In our previous work, we have analyzed the various biochemical pathways, and we found Ketol Acid Reducto Isomerase (KARI) an enzyme involves in the amino acid biosynthesis, could be a better target. This enzyme was found to be unique by comparing to host proteome through BLASTp analysis. A homology based model of KARI was generated by Swiss model server. The generated model had been validated by PROCHECK and WHAT IF programs. The Zinc library was generated within the limitation of the Lipinski rule of five, for docking study. Based on the dock-score six molecules have been studied for ADME/TOX analysis and subjected for pharmacophore model generation. The Zinc ID of the potential inhibitors is ZINC00720614, ZINC01068126, ZINC0923, ZINC02090678, ZINC00663057 and ZINC02284065 and found to be pharmacologically active agonist and antagonist of KARI. This study is an attempt to Insilco evaluation of the KARI as a drug target and the screened inhibitors could help in the development of the better drug against Aspergillus. PMID- 22300396 TI - Integration of data from multiple sources for simultaneous modelling analysis: experience from nevirapine population pharmacokinetics. AB - AIMS: To propose a modelling strategy to efficiently integrate data from different sources in one simultaneous analysis, using nevirapine population pharmacokinetic data as an example. METHODS: Data from three studies including 115 human immunodeficiency virus-infected South African adults were used. Patients were on antiretroviral therapy regimens including 200 mg nevirapine twice daily and sampled at steady state. A development process was suggested, implemented in NONMEM7 and the final model evaluated with an external data set. RESULTS: A stepwise approach proved efficient. Model development started with the intensively sampled data. Data were added sequentially, using visual predictive checks for inspecting their compatibility with the existing model. Covariate exploration was carried out, and auxiliary regression models were designed for imputation of missing covariates. Nevirapine pharmacokinetics was described by a one-compartment model with absorption through two transit compartments. Body size was accounted for using allometric scaling. The model included a mixture of two subpopulations with different typical values of clearance, namely fast (3.12 l h( 1)) and slow metabolizers (1.45 l h(-1)), with 17% probability of belonging to the latter. Absorption displayed large between-occasion variability, and food slowed the absorption mean transit time from 0.6 to 2.5 h. Concomitant antitubercular treatment including rifampicin typically decreased bioavailability by 39%, with significant between-subject variability. Visual predictive checks of external validation data indicated good predictive performance. CONCLUSIONS: The development strategy succeeded in integrating data from different sources to produce a model with robust parameter estimates. This work paves the way for the creation of a nevirapine mega-model, including additional data from numerous diverse sources. PMID- 22300398 TI - Short-term memory treatment: patterns of learning and generalisation to sentence comprehension in a person with aphasia. AB - Auditory-verbal short-term memory deficits (STM) are prevalent in aphasia and can contribute to sentence comprehension deficits. This study investigated the effectiveness of a novel STM treatment in improving STM (measured with span tasks) and sentence comprehension (measured with the Token Test and the Test for the Reception of Grammar, TROG) in a person with severe aphasia (transcortical motor). In particular, the research questions were: (1) Would STM training improve STM? (2) Would improvements from the STM training generalise to improvements in comprehension of sentences? STM was trained using listening span tasks of serial word recognition. No other language or sentence comprehension skills were trained. Following treatment, STM abilities improved (listening span, forward digit span). There was also evidence of generalisation to untreated sentence comprehension (only on the TROG). Backward digit span, phonological processing and single word comprehension did not improve. Improvements in sentence comprehension may have resulted from resilience to rapid decay of linguistic representations within sentences (words and phrases). This in turn facilitated comprehension. PMID- 22300399 TI - Broadband enhancement in thin-film amorphous silicon solar cells enabled by nucleated silver nanoparticles. AB - Recently plasmonic effects have gained tremendous interest in solar cell research because they are deemed to be able to dramatically boost the efficiency of thin film solar cells. However, despite of the intensive efforts, the desired broadband enhancement, which is critical for real device performance improvement, has yet been achieved with simple fabrication and integration methods appreciated by the solar industry. We propose in this paper a novel idea of using nucleated silver nanoparticles to effectively scatter light in a broadband wavelength range to realize pronounced absorption enhancement in the silicon absorbing layer. Since it does not require critical patterning, experimentally these tailored nanoparticles were achieved by the simple, low-cost and upscalable wet chemical synthesis method and integrated before the back contact layer of the amorphous silicon thin-film solar cells. The solar cells incorporated with 200 nm nucleated silver nanoparticles at 10% coverage density clearly demonstrate a broadband absorption enhancement and significant superior performance including a 14.3% enhancement in the short-circuit photocurrent density and a 23% enhancement in the energy conversion efficiency, compared with the randomly textured reference cells without nanoparticles. Among the measured plasmonic solar cells the highest efficiency achieved was 8.1%. The significant enhancement is mainly attributed to the broadband light scattering arising from the integration of the tailored nucleated silver nanoparticles. PMID- 22300400 TI - Donor brain death inhibits tolerance induction in miniature swine recipients of fully MHC-disparate pulmonary allografts. AB - We have previously shown that a short course of high-dose tacrolimus induces long term tolerance to fully mismatched lung allografts procured from healthy MHC inbred miniature swine. Here, we investigate whether donor brain death affects tolerance induction. Four recipient swine were transplanted with fully mismatched lung grafts from donors that were rendered brain dead and mechanically ventilated for 4 h before procurement (Group 1). These recipients were compared to two control groups (Group 2: 4 h of donor ventilation without brain death [n = 5]; and Group 3: no donor brain death with <1 h of ventilation [n = 6]). All recipients were treated with a 12-day course of tacrolimus. In contrast to both groups of control animals, the swine transplanted with lung allografts from brain dead donors all rejected their grafts by postoperative day 45 and showed persistent responsiveness to donor antigen by MLR. Several additional swine underwent brain death induction and/or mechanical ventilation alone to determine the effects of these procedures on the expression of proinflammatory molecules. Significant increases in serum concentrations of IL-1, TNF-alpha and IL-10 were seen after brain death. Upregulation of IL-1 and IL-6 gene expression was also observed. PMID- 22300401 TI - Transmission of the major skin microbiota, Malassezia, from mother to neonate. AB - BACKGROUND: Skin surface colonization starts after birth. It is thought that early microbial colonization affects the development of skin immune functions. Although Malassezia is the predominant fungus in the skin microbiota in healthy individuals, the microorganism is associated with atopic dermatitis and seborrheic dermatitis. In the present study, transmission of skin microbiota from mothers to their neonates was elucidated using the Malassezia microbiota as an indicator. METHODS: Temporal changes in the level of Malassezia colonization of the skin from 27 neonates and mothers were investigated by real-time polymerase chain reaction assay. The genotypes of Malassezia colonizing the neonate and mother were also determined. RESULTS: Malassezia was detected from 89% and 100% of neonate samples on days 0 and 1 after birth, respectively. Subsequently, the level of Malassezia colonization of the neonates increased with time, whereas that of the mothers did not change. The Malassezia diversity of neonates shifted to the adult type by day 30. The genotype of Malassezia colonizing the skin of neonates agreed well with that of Malassezia colonizing the skin of the mothers. CONCLUSION: Fungal microbiota colonization of neonates began on day 0, and the fungal microbiota of neonates had changed to the adult type by day 30. To our knowledge, this is the first report of a molecular analysis of the fungal microbiota of neonates. PMID- 22300402 TI - Birth order effect on childhood food allergy. AB - Higher birth order is associated with a smaller risk of allergy (birth order effect). The purpose of this study was to compare the significance of the birth order effect on the prevalence of specific allergic diseases [bronchial asthma (BA), atopic dermatitis (AD), allergic rhinitis (AR), allergic conjunctivitis (AC), and food allergy (FA)] among schoolchildren. A questionnaire survey dealing with the prevalence of allergic diseases was administered to the parents of 14,669 schoolchildren aged 7-15 yr. Based on the data, the prevalence of each allergic disease was compared according to birth order (1st, 2nd, and 3rd or later). Multiple regression analysis was performed to test the significance of the differences. There was no significant difference in the prevalence of BA or AD according to birth order. The prevalence of AR, AC, and FA decreased significantly as birth order increased. The prevalence of FA among those with 1st, 2nd, and 3rd or later birth order was 4.0%, 3.4%, and 2.6%, respectively (p = 0.01). With respect to symptoms in infancy, the prevalence of wheeze increased significantly and that of FA and eczema in infancy decreased significantly as birth order increased. The present data show a significant birth order effect on FA. The effect was also observed for the prevalence of FA and eczema in infancy. These data support the concept of early, non-allergen-specific programming of IgE mediated immunity. PMID- 22300403 TI - Cutaneous id reactions: a comprehensive review of clinical manifestations, epidemiology, etiology, and management. AB - Id reactions are a type of secondary inflammatory reaction that develops from a remote localized immunological insult. To date, id reactions caused by various fungal, bacterial, viral, and parasitic infections have been reported. Superficial fungal infections, especially tinea pedis, are the most common cause of id reactions. Id reactions exhibit multiple clinical presentations, including localized or widespread vesicular lesions, maculopapular or scarlatiniform eruptions, erythema nodosum, erythema multiforme, erythema annulare centrifugum, Sweet's syndrome, guttate psoriasis, and autoimmune bullous disease. The mechanisms underlying id reactions vary depending on the type of clinical presentation. The most important aspect of therapy involves the identification and adequate treatment of the underlying infection or dermatitis. This review comprehensively discusses the current state of the field concerning cutaneous id reactions, including diagnostic criteria, clinical presentations, underlying infectious conditions, etiologic agents, immunologic characteristics, histopathologic findings, and management strategies. PMID- 22300404 TI - Medial rectus Botox injection with pterygium excision and autograft as a novel technique for management of recurrent pterygium. PMID- 22300405 TI - Do epigenetic pathways initiate late onset Alzheimer disease (LOAD): towards a new paradigm. AB - Late onset Alzheimer's disease (LOAD) is a non-familial, progressive neurodegenerative disease and the most prominent form of dementia in the elderly. Accumulating evidence suggests that LOAD not only results from the combined effects of variation in a number of genes and environmental factors, but also from epigenetic abnormalities such as histone modifications or DNA methylation. In comparison to monogenic diseases, LOAD exhibits numerous anomalies that suggest an epigenetic component in disease etiology. Evidence against a monogenic course and for an epigenetic component include: 1) the dominance of sporadic cases over familial ones and the low estimated concordance rates for monozygotic twins; 2) gender specific susceptibility and course of disease; 3) parent-of origin effects, and late age of onset; 4) brain chromatin abnormalities, non Mendelian inheritance patterns, and atypical levels of folate and homocysteine; and 5) monoallelic expression patterns of susceptibility genes [1]. The epigenome is particularly susceptible to deregulation during early embryonic and neonatal periods and thus disturbances during these periods can have latent lasting effects. The Latent Early-life Associated Regulation (LEARn) model attempts to explain these consequences from a brain specific point of view. In the present review we present the evidence that support the role of epigenetics in the development of AD and explore the potential pathways and mechanisms that may be involved. PMID- 22300406 TI - Applying epigenetics to Alzheimer's disease via the latent early-life associated regulation (LEARn) model. AB - Alzheimer's disease (AD) is a leading cause of aging related dementia and has been extensively studied by several groups around the world. A general consensus, based on neuropathology, genetics and cellular and animal models, is that the 4 kDa amyloid beta protein (Abeta) triggers a toxic cascade that induces microtubule-associated protein tau (MAPT) hyperphosphorylation and deposition. Together, these lesions lead to neuronal dysfunction and neurodegeneration, modeled in animals, that ultimately causes dementia. Genetic studies show that a simple duplication of the Abeta precursor (APP) gene, as occurs in Down syndrome (trisomy 21), with a 1.5-fold increase in expression, can cause dementia with the complete AD associated neuropathology. The most fully characterized form of AD is early onset familial AD (FAD). Unfortunately, by far the most common form of AD is late onset AD (LOAD). FAD has well-identified autosomally dominant genetic causes, absent in LOAD. It is reasonable to hypothesize that environmental influences play a much stronger role in etiology of LOAD than of FAD. Since AD pathology in LOAD closely resembles FAD with accumulation of both Abeta and MAPT, it is likely that the environmental factors foster accumulation of these proteins in a manner similar to FAD mutations. Therefore, it is important to identify environmentally driven changes that "phenocopy" FAD in order to find ways to prevent LOAD. Epigenetic changes in expression are complex but stable determinants of many complex traits. Some aspects are regulated by prenatal and early post-natal development, others punctuate specific periods of maturation, and still others occur throughout life, mediating predictable changes that take place during various developmental stages. Environmental agents such as mercury, lead, and pesticides can disrupt the natural epigenetic program and lead to developmental deficits, mental retardation, feminization, and other complex syndromes. In this review we discuss latent early- life associated regulation (LEARn), where apparently temporary changes, induced by environmental agents, become latent and present themselves again at maturity or senescence to increase production of Abeta that may cause AD. The model provides us with a novel direction for identifying potentially harmful agents that may induce neurodegeneration and dementia later in life and provides hope that we may be able to prevent age-related neurodegenerative disease by "detoxifying" our environment. PMID- 22300407 TI - A finite element analysis of the vibration behaviour of a cementless hip system. AB - An early diagnosis of aseptic loosening of a total hip replacement (THR) by plain radiography, scintigraphy or arthography has been shown to be less reliable than using a vibration technique. However, it has been suggested that it may be possible to distinguish between a secure and a loose prosthesis using a vibration technique. In fact, vibration analysis methods have been successfully used to assess dental implant stability, to monitor fracture healing and to measure bone mechanical properties. Several studies have combined the vibration technique with the finite element (FE) method in order to better understand the events involved in the experimental technique. In the present study, the main goal is to simulate the change in the resonance frequency during the osseointegration process of a cementless THR (Zweymuller). The FE method was used and a numerical modal analysis was conducted to obtain the natural frequencies and mode shapes under vibration. The effects were studied of different bone and stem material properties, and different contact conditions at the bone-implant interface. The results were in agreement with previous experimental and computational observations, and differences among the different cases studied were detected. As the osseointegration process at the bone-implant interface evolved, the resonance frequency values of the femur-prosthesis system also increased. In summary, vibration analysis combined with the FE method was able to detect different boundary conditions at the bone-implant interface in cases of both osseointegration and loosening. PMID- 22300408 TI - Recipient IL28B polymorphism is an important independent predictor of posttransplant diabetes mellitus in liver transplant patients with chronic hepatitis C. AB - IL28B polymorphisms are strongly associated with response to treatment for HCV infection. IL28B acts on interferon-stimulated genes via the JAK-STAT pathway, which has been implicated in development of insulin resistance. We investigated whether IL28B polymorphisms are associated with posttransplant diabetes mellitus (DM). Consecutive HCV patients who underwent liver transplantation between 1-1995 and 1-2011 were studied. Genotyping of the polymorphism rs12979860 was performed on DNA collected from donors and recipients. Posttransplant DM was screened for by fasting blood glucoses every 1-3 months. Of 221 included patients, 69 developed posttransplant DM (31%). Twenty-two patients with recipient IL28B genotype TT (48%), 25 with IL28B genotype CT (25%) and 22 with IL28B genotype CC (29%) developed posttransplant DM. TT genotype was statistically significantly associated with posttransplant DM over time (log rank p = 0.012 for TT vs. CT and p = 0.045 for TT vs. CC). Multivariate Cox regression analysis correcting for donor age, body mass index, baseline serum glucose, baseline serum cholesterol, recipient age and treated rejection, showed that recipient IL28B genotype TT was independently associated with posttransplant DM (hazard ratio 2.51; 95% confidence interval 1.17-5.40; p = 0.011). We conclude that the risk of developing posttransplant DM is significantly increased in recipients carrying the TT polymorphism of the IL28B gene. PMID- 22300410 TI - Association between obesity and alteration of sperm DNA integrity and mitochondrial activity. AB - What's known on the subject? and What does the study add? The relationship between high levels of BMI and changes in altered standard semen analysis parameters are described in the literature. However, the functional characteristics of the sperm are essential to complete the evaluation of male infertility. Thus, this study provides important information about the functionality of the sperm of men with different levels of BMI. OBJECTIVE: To assess the effect of obesity on semen analysis, sperm mitochondrial activity and DNA fragmentation. MATERIALS AND METHODS: A transversal study of 305 male patients, presenting for clinical evaluation, was carried out. The patients were divided into three groups according to body mass index (BMI) as follows: eutrophic (BMI < 25 kg/m(2), n = 82), overweight (BMI >= 25 kg/m(2) and <30, n = 187) and obese (BMI >= 30 kg/m(2), n = 36). The variables analysed were semen analysis, rate of sperm DNA fragmentation and sperm mitochondrial activity. Groups were compared using one-way analysis of variance followed by a least significant difference post-hoc test. A P-value of <0.05 was considered to indicate statistical significance. RESULTS: No differences were observed in age, ejaculatory abstinence, ejaculate volume, sperm vitality, morphology or round cell and neutrophil count among the groups. The eutrophic group had a higher percentage of sperm with progressive motility (P = 0.001). Mitochondrial activity was lower in the obese group (P = 0.037) when compared to the eutrophic, and the percentage of sperm with DNA damage was higher in the obese group (P = 0.004) than the other two groups. CONCLUSION: Increased BMI values are associated with decreased mitochondrial activity and progressive motility and increased DNA fragmentation. PMID- 22300409 TI - Astroglial pentose phosphate pathway rates in response to high-glucose environments. AB - ROS (reactive oxygen species) play an essential role in the pathophysiology of diabetes, stroke and neurodegenerative disorders. Hyperglycaemia associated with diabetes enhances ROS production and causes oxidative stress in vascular endothelial cells, but adverse effects of either acute or chronic high-glucose environments on brain parenchymal cells remain unclear. The PPP (pentose phosphate pathway) and GSH participate in a major defence mechanism against ROS in brain, and we explored the role and regulation of the astroglial PPP in response to acute and chronic high-glucose environments. PPP activity was measured in cultured neurons and astroglia by determining the difference in rate of (14)CO(2) production from [1-(14)C]glucose and [6-(14)C]glucose. ROS production, mainly H(2)O(2), and GSH were also assessed. Acutely elevated glucose concentrations in the culture media increased PPP activity and GSH level in astroglia, decreasing ROS production. Chronically elevated glucose environments also induced PPP activation. Immunohistochemical analyses revealed that chronic high-glucose environments induced ER (endoplasmic reticulum) stress (presumably through increased hexosamine biosynthetic pathway flux). Nuclear translocation of Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2), which regulates G6PDH (glyceraldehyde-6-phosphate dehydrogenase) by enhancing transcription, was also observed in association with BiP (immunoglobulin heavy-chain-binding protein) expression. Acute and chronic high-glucose environments activated the PPP in astroglia, preventing ROS elevation. Therefore a rapid decrease in glucose level seems to enhance ROS toxicity, perhaps contributing to neural damage when insulin levels given to diabetic patients are not properly calibrated and plasma glucose levels are not adequately maintained. These findings may also explain the lack of evidence for clinical benefits from strict glycaemic control during the acute phase of stroke. PMID- 22300412 TI - Pityriasis amiantacea: a distinctive presentation of psoriasis associated with tumour necrosis factor-alpha inhibitor therapy. AB - Pityriasis amiantacea (PA; also known as tinea amiantacea) is a relatively rare but distinctive scalp condition characterized by thick scales that adhere to each other and to the hair shaft, resulting in agglomeration and matting of hair. Temporary alopecia is a common complication. Although a specific cause remains unclear, PA is associated with several inflammatory diseases such as psoriasis and seborrhoeic dermatitis. We present a case of PA as a complication of underlying psoriasis, which developed during tumour necrosis factor (TNF)-alpha inhibitor therapy for Crohn disease. This paradoxical cutaneous reaction to anti TNF-alpha therapy has been recently described as an emerging and perplexing cause of psoriasis and psoriasiform eruptions. PMID- 22300411 TI - Suppressive regulation of KSHV RTA with O-GlcNAcylation. AB - BACKGROUND: The replication and transcription activator (RTA) of Kaposi's sarcoma associated herpesvirus (KSHV) is a molecular switch that initiates a productive replication of latent KSHV genomes. KSHV RTA (K-RTA) is composed of 691 amino acids with high Ser and Thr content (17.7%), but to what extent these Ser and Thr are modified in vivo has not been explored. METHODS: By using tandem mass spectrometric analysis of affinity-purified FLAG tagged K-RTA, we sought to identify Ser and Thr residues that are post-translationally modified in K-RTA. RESULTS: We found that K-RTA is an O-GlcNAcylated protein and Thr-366/Thr-367 is the primary motif with O-GlcNAcylation in vivo. The biological significance of O GlcNAc modified Thr-366 and Thr-367 was assessed by site-specific amino acid substitution. Replacement of Thr with Ala at amino acid 366 or 367 caused a modest enhancement of K-RTA transactivation activity in a luciferase reporter assay and a cell model for KSHV reactivation. By using co-immunoprecipitation coupled with western blot analysis, we showed that the capacity of K-RTA in associating with endogenous PARP1 was significantly reduced in the Thr-366/Thr 367 O-GlcNAc mutants. PARP1 is a documented negative regulator of K-RTA that can be ascribed by the attachment of large negatively charged polymer onto K-RTA via PARP1's poly (ADP-ribose) polymerase activity. In agreement, shRNA-mediated depletion of O-GlcNAc transferase (OGT) in KSHV infected cells augmented viral reactivation and virus production that was accompanied by diminished K-RTA and PARP1 complexes. CONCLUSIONS: KSHV latent-lytic switch K-RTA is modified by cellular O-GlcNAcylation, which imposes a negative effect on K-RTA transactivation activity. This inhibitory effect involves OGT and PARP1, two nutritional sensors recently emerging as chromatin modifiers. Thus, we speculate that the activity of K-RTA on its target genes is continuously checked and modulated by OGT and PARP1 in response to cellular metabolic state. PMID- 22300413 TI - The Aouda.X space suit simulator and its applications to astrobiology. AB - We have developed the space suit simulator Aouda.X, which is capable of reproducing the physical and sensory limitations a flight-worthy suit would have on Mars. Based upon a Hard-Upper-Torso design, it has an advanced human-machine interface and a sensory network connected to an On-Board Data Handling system to increase the situational awareness in the field. Although the suit simulator is not pressurized, the physical forces that lead to a reduced working envelope and physical performance are reproduced with a calibrated exoskeleton. This allows us to simulate various pressure regimes from 0.3-1 bar. Aouda.X has been tested in several laboratory and field settings, including sterile sampling at 2800 m altitude inside a glacial ice cave and a cryochamber at -110 degrees C, and subsurface tests in connection with geophysical instrumentation relevant to astrobiology, including ground-penetrating radar, geoacoustics, and drilling. The communication subsystem allows for a direct interaction with remote science teams via telemetry from a mission control center. Aouda.X as such is a versatile experimental platform for studying Mars exploration activities in a high-fidelity Mars analog environment with a focus on astrobiology and operations research that has been optimized to reduce the amount of biological cross contamination. We report on the performance envelope of the Aouda.X system and its operational limitations. PMID- 22300414 TI - Poly(lactide-co-glycolide)-laponite-F68 nanocomposite vesicles through a single step double-emulsion method for the controlled release of doxorubicin. AB - Poly(lactide-co-glycolide) (PLGA)-laponite-F68 nanocomposite (PNC) vesicles were prepared through a technically facile, single-step water/oil/water double emulsion method using ethyl acetate/water mixture. Vesicles of diameter 100 nm to 1.2 MUm and average membrane thickness 30 nm were produced. Encapsulation with chemotherapeutic drug doxorubicin revealed unilamellar nature of the vesicle wall. PNC exhibited exfoliated morphology, enhanced thermal stability over neat PLGA, and a glass transition temperature of 54.29 degrees C. The zeta potential of -14.1 +/- 0.231 for the vesicles revealed that the negatively charged PLGA surface is covered with neutral F68 in the vesicle wall. F68-Assisted formation of water/oil/water double emulsion of PNC in ethyl acetate/water mixture is proposed for the formation of the vesicles. Release characteristics of doxorubicin in phosphate-buffered saline (pH 7.4), cytotoxicity of bare and drug loaded PNC vesicles with L929 cells, and uptake of doxorubicin with C6 fibroblast glioma cell line were also investigated. PMID- 22300415 TI - Enhance the dissolution rate and oral bioavailability of pranlukast by preparing nanosuspensions with high-pressure homogenizing method. AB - PURPOSE: Pranlukast, one of the potential therapeutic tools in the treatment of asthma, has limited clinical applications due to its poor water solubility. The study is aimed to provide a platform for better utilizing pranlukast with enhancement of the dissolution rate and, thus, the oral bioavailability of pranluka'st by preparing nanosuspensions through high-pressure homogenization method. METHOD: Poloxamer407 and PEG200 were chosen as stabilizer and surfactant. The formulation was investigated systematically with the dissolution tests as predominant method. Nanosuspensions were prepared by programmed high-pressure homogenization method. The product was characterized by particle size analysis, TEM and XRD are evaluated by in vitro dissolution tests and in vivo absorption examination. In addition, nanosuspensions with only pranlukast were prepared and compared with formulated nanosuspensions. RESULTS: The optimal values of formulation were 0.5% (w/v) pranlukast with 0.375% (w/v) Poloxamer407, 0.375% (w/v) PEG200 and the screened programming homogenizing procedure parameters were 680 bar for the first 15 circles, 1048 bar for the next 9 circles and 1500 bar for the last 9 circles. Nanosuspensions of 318.2 +/- 7.3 nm, -29.3 +/- 0.8 mV were obtained. The XRD analysis indicated no change of crystalline occurred in the process of homogenization. The in vitro dissolution behavior of nanosuspensions exhibited complete release in 30 min with a remarkable fast dissolution rate. The in vivo bioavailability of formulated pranlukast nanosuspensions demonstrated its enhancement of fast onset of therapeutic drug effects with 4.38-fold improved compared to that of raw crystals. CONCLUSION: The study provides a feasible, practical thinking of industry development in the clinical use of pranlukast. PMID- 22300416 TI - The effectiveness of a standardised preoperative preparation in reducing child and parent anxiety: a single-blind randomised controlled trial. AB - AIMS: To evaluate the effect of a structured preoperative preparation on child and parent state anxiety, child behavioural change and parent satisfaction. BACKGROUND: It is estimated that around 50-70% of hospitalised children experience severe anxiety and distress prior to surgery. Children who are highly anxious and distressed preoperatively are likely to be distressed on awakening and have negative postoperative behaviour. Although education before surgery has been found to be useful mostly in North America, the effectiveness of preoperative preparation programme adapted to the Australian context remains to be tested. DESIGN: This single-blind randomised controlled study was conducted at a tertiary referral hospital for children in Western Australia. METHODS: Following ethics approval and parental consent, 73 children and one of their carers (usually a parent) were randomly assigned into two groups. The control group had standard practice with no specific preoperative education and the experimental group received a preoperative preparation, including a photo file, demonstration of equipment using a role-modelling approach and a tour. RESULTS: The preoperative preparation reduced parent state anxiety significantly (-2.32, CI -4.06 to -0.56, p = 0.009), but not child anxiety (-0.59, CI -1.23 to 0.06, p = 0.07). There was no significant difference in child postoperative behaviour or parent satisfaction between the groups. There was a significant two-point pain score reduction in the preoperative preparation group, when compared with the control group median 2 (IQR 5) and 4 (IQR 4), respectively (p = 0.001). CONCLUSIONS: Preoperative preparation was more efficient on parent than child. Although the preoperative preparation had limited effect on child anxiety, it permitted to decrease pain experience in the postoperative period. RELEVANCE TO CLINICAL PRACTICE: Parents should be actively involved in their child preoperative preparation. PMID- 22300417 TI - 5d early-transition-metal corroles: a trioxo-bridged binuclear tungsten(VI) derivative. AB - The synthesis and full characterization of the first tungsten corrole reveal that it is a binuclear trioxo-bridged complex of tungsten(VI), a coordination motif without precedence for tungsten chelated by other ligands. PMID- 22300418 TI - Mandibular distraction in neonates: indications, technique, results. AB - BACKGROUND: The Pierre Robin Sequence features were first described by Robin in 1923 and include micrognathia, glossoptosis and respiratory distress with an incidence estimated as 1:8,500 to 1:20,000 newborns. Upper airway obstruction and feeding difficulties are the main concerns related to the pathology. Mandibular distraction should be considered a treatment option (when other treatments result inadequate). PATIANTS AND METHODS: Ten patients between the ages of 1 month and 2 years with severe micrognathia and airway obstruction were treated with Mandibular Distraction Osteogenesis (MDO).All patients underwent fibroscopic examination of the upper airway and a radiographic imaging and/or computed tomography scans to detect malformations and to confirm that the obstruction was caused by posterior tongue displacement. All patients were evaluated by a multidisciplinary team. Indications for surgery included frequent apneic episodes with severe desaturation (70%). Gavage therapy was employed in all patients since oral feeding was not possible. The two tracheotomy patients were 5 months and 2 years old respectively, and the distraction procedure was performed to remove the tracheotomy tube. All patients were treated with bilateral mandibular distraction: two cases with an external multivector distraction device, six cases with an internal non-resorbable device and two cases with an internal resorbable device. In one case, the patient with Goldenhar's Syndrome, the procedure was repeated. RESULTS: The resolution of symptoms was obtained in all patients, and, when present, tracheotomy was removed without complications. Of the two patients with pre-existing tracheotomies, in the younger patient (5 months old) the tracheotomy was removed 7 days postoperatively. In the Goldenhar's syndrome case (2 years old) a Montgomery device was necessary for 6 months due to the presence of tracheotomy-inducted tracheomalacia. Patients were discharged when the endpoint was obtained: symptoms and signs of airway obstruction were resolved, PAS and maxillomandibular relationship improved, and tracheotomy, when present, removed. During the follow-up, no injury to the inferior alveolar nerve was noted and scarring was significant in only the two cases treated with external devices. CONCLUSION: Mandibular Distraction Osteogenesis is a good solution in solving respiratory distress when other procedures are failed in paediatric patients with severe micrognatia. PMID- 22300419 TI - Scaling of pharmacokinetics across paediatric populations: the lack of interpolative power of allometric models. AB - AIM: The objective of this investigation was to assess the performance of an allometric model as the basis for interpolating drug exposure in the context of pharmacokinetic bridging across paediatric subpopulations. METHODS: Midazolam was selected as a paradigm compound. Two nonlinear mixed effects models were developed to describe midazolam pharmacokinetics in infants, toddlers and adults (model 1) and in children and adolescents (model 2). Subsequently, systemic drug exposure, expressed in terms of the area under the concentration vs. time curve (AUC), in children and adolescents was interpolated based on pharmacokinetic parameter distributions obtained from the model describing infants, toddlers and adults (model 1). Results were compared with the values obtained from modelling of the data in the corresponding population (model 2). RESULTS: The two pharmacokinetic models accurately described midazolam exposure in the population on which they were built. However, the model based on data from infants, toddlers and adults failed to predict the exposure observed in children and adolescents: the mean difference between the predicted and estimated AUC(0-180) was of -17.8%, with a range of -6.8 to -38.4%.The discrepancy between estimated and interpolated exposure increased proportionally with body weight. CONCLUSIONS: The current results indicate that irrespective of whether extrapolation or interpolation methods are to be applied during paediatric drug development, model predictions beyond the range of the data used for parameter estimation may be biased. For accurate inter- or extrapolation to different populations, the assumption of identical parameter-covariate correlations across age groups may not be taken for granted. PMID- 22300420 TI - Acute genital ulcers in nonsexually active young girls: case series, review of the literature, and evaluation and management recommendations. AB - Acute genital ulcers rarely occur in nonsexually active young girls. When present, they can cause significant physical and emotional distress for the patient and her parents, and prompt an evaluation for sexual abuse and sexually transmitted diseases. With this review, we aim to further characterize acute genital ulcers in nonsexually active young girls by reviewing the medical records of patients with this disorder and to offer an approach to the diagnosis, evaluation, and treatment of acute genital ulcers based on our understanding and knowledge of this condition. We retrospectively review our understanding and knowledge of acute genital ulcers in nonsexually active girls at a pediatric hospital. A review of the recent literature on acute genital ulcers and a multidisciplinary approach to the diagnosis, evaluation, and treatment of acute genital ulcers are also presented. Twelve patients presented with acute genital ulcers, 11 of which were hospitalized for evaluation and pain management. Extensive work-up failed to reveal a specific infectious or autoimmune etiology in all but one patient, who was diagnosed with acute mycoplasma pneumonia. Acute genital ulcers in nonsexually active young girls likely represent a form of idiopathic vulvar aphthosis. Evaluation of a first episode of acute genital ulcers with mild prodromal symptoms should be limited. Treatment consists primarily of supportive care and symptom relief. PMID- 22300421 TI - The transitional heterojunction behavior of PbS/ZnO colloidal quantum dot solar cells. AB - The nature of charge separation at the heterojunction interface of solution processed lead sulphide-zinc oxide colloidal quantum dot solar cells is investigated using impedance spectroscopy and external quantum efficiency measurements to examine the effect of varying the zinc oxide doping density. Without doping, the device behaves excitonically with no depletion region in the PbS layer such that only charge carriers generated within a diffusion length of the PbS/ZnO interface have a good probability of being harvested. After the ZnO is photodoped such that the doping density is near or greater than that of the PbS, a significant portion of the depletion region is found to lie within the PbS layer increasing charge extraction (p-n operation). PMID- 22300422 TI - Mathematical modeling of solid cancer growth with angiogenesis. AB - BACKGROUND: Cancer arises when within a single cell multiple malfunctions of control systems occur, which are, broadly, the system that promote cell growth and the system that protect against erratic growth. Additional systems within the cell must be corrupted so that a cancer cell, to form a mass of any real size, produces substances that promote the growth of new blood vessels. Multiple mutations are required before a normal cell can become a cancer cell by corruption of multiple growth-promoting systems. METHODS: We develop a simple mathematical model to describe the solid cancer growth dynamics inducing angiogenesis in the absence of cancer controlling mechanisms. RESULTS: The initial conditions supplied to the dynamical system consist of a perturbation in form of pulse: The origin of cancer cells from normal cells of an organ of human body. Thresholds of interacting parameters were obtained from the steady states analysis. The existence of two equilibrium points determine the strong dependency of dynamical trajectories on the initial conditions. The thresholds can be used to control cancer. CONCLUSIONS: Cancer can be settled in an organ if the following combination matches: better fitness of cancer cells, decrease in the efficiency of the repairing systems, increase in the capacity of sprouting from existing vascularization, and higher capacity of mounting up new vascularization. However, we show that cancer is rarely induced in organs (or tissues) displaying an efficient (numerically and functionally) reparative or regenerative mechanism. PMID- 22300423 TI - Varenicline as a smoking cessation aid in a Greek population: a subanalysis of an observational study. AB - BACKGROUND: Greece has the highest proportion of smokers in the European Union with 42% of Greeks admitting that they smoke, based on a 2009 survey. This post hoc analysis of a prospective, observational study evaluated the effectiveness and safety profile of the smoking cessation aid varenicline, as well as potential predictors of quit success in a Greek population. METHODS: Participants were prescribed varenicline according to the recommendations of the European Summary of Product Characteristics (1 mg twice daily). The 7-day point prevalence of abstinence at Week 12 was determined based on verbal reporting using a nicotine use inventory. Abstinence was confirmed by carbon monoxide measurements of exhaled air at the last visit of the study. The safety profile of varenicline was also assessed. RESULTS: At baseline, the Greek subsample (n = 196) had a mean age of 42.6 years, with 54.6% of them being men. Participants had a smoking history of 23.5 years and a Fagerstrom Test for Nicotine Dependence total score of 6.6. After 12 weeks of varenicline therapy, 70.4% (95% CI, 64.0-76.7) of all participants had quit smoking. This increased to 86.2% among participants who had taken the study medication for 80% of the planned number of treatment days. Age was a significant predictor of quit success. The most frequently observed treatment-emergent adverse event was nausea, occurring in 13.3% of participants. CONCLUSIONS: In this 'real-world' observational study, 70.4% of Greek smokers successfully quit smoking after 12 weeks of varenicline therapy, providing support that varenicline is an effective smoking cessation medication. Further studies with longer follow-up are warranted. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00669240. PMID- 22300424 TI - Infantile systemic hyalinosis associated with a putative splice-site mutation in the ANTXR2 gene. AB - Infantile systemic hyalinosis (ISH) is a rare autosomal recessive genetic disorder characterized by dermal and subcutaneous fibromatosis, joint contractures and bone deformities. The condition usually presents at birth, resulting in death in infancy. ISH is caused by mutations in the anthrax toxin receptor 2 gene, ANTXR2, also known as CMG2. We report an Indian child with ISH in whom we identified a homozygous acceptor splice site mutation, IVS2-4G>A. In silico analysis of this sequence showed that it changed predicted cryptic splicing, leading to out-of-frame transcripts and little, if any, functional protein. Mutations in the ANTXR2 gene can also cause juvenile hyaline fibromatosis (JHF). Although there are currently no effective treatments for ISH or JHF, identification of pathogenetic mutations in the ANTXR2 gene makes DNA based prenatal diagnosis feasible for subsequent pregnancies. PMID- 22300425 TI - Which factors influence the ability of a computational model to predict the in vivo deformation behaviour of skeletal muscle? AB - Deep tissue injury (DTI) is a severe form of pressure ulcer where tissue damage starts in deep tissues underneath intact skin. Tissue deformation may play an important role in the aetiology, which can be investigated using an experimental numerical approach. Recently, an animal-specific finite element model has been developed to simulate experiments in which muscle tissue was compressed with an indenter. In this study, the material behaviour and boundary conditions were adapted to improve the agreement between model and experiment and to investigate the influence of these adaptations on the predicted strain distribution. The use of a highly nonlinear material law and including friction between the indenter and the muscle both improved the quality of the model and considerably influenced the estimated strain distribution. With the improved model, the required sample size to detect significant differences between loading conditions can be diminished, which is clearly relevant in experiments involving animals. PMID- 22300426 TI - Circulating antibody free light chains and risk of posttransplant lymphoproliferative disorder. AB - Posttransplant lymphoproliferative disorder (PTLD) is a major complication of solid-organ transplantation. With human immunodeficiency virus infection (an analogous immunosuppressive state), elevated kappa and lambda immunoglobulin free light chains (FLCs) in peripheral blood are associated with increased risk of lymphoma. To assess the role of B-cell dysfunction in PTLD, we measured circulating FLCs among Canadian transplant recipients, including 29 individuals with PTLD and 57 matched transplant recipients who were PTLD-free. Compared with controls, PTLD cases had higher kappa FLCs (median 1.53 vs. 1.07 times upper limit of normal) and lambda FLCs (1.03 vs. 0.68). Using samples obtained on average 3.5 months before PTLD diagnosis, cases were more likely to have polyclonal FLC elevations (i.e. elevated kappa and/or lambda with normal kappa/lambda ratio: odds ratio [OR] 4.2, 95%CI 1.1-15) or monoclonal elevations (elevated kappa and/or lambda with abnormal ratio: OR 3.0, 95%CI 0.5-18). Strong FLC-PTLD associations were also observed at diagnosis/selection. Among recipients with Epstein-Barr virus (EBV) DNA measured in blood, EBV DNAemia was associated with FLC abnormalities (ORs 6.2 and 3.2 for monoclonal and polyclonal elevations). FLC elevations are common in transplant recipients and associated with heightened PTLD risk. FLCs likely reflect B-cell dysfunction, perhaps related to EBV-driven lymphoproliferation. PMID- 22300427 TI - Clinical characteristics of neonates with VACTERL association. AB - BACKGROUND: The VACTERL association (VA) is the non-random co-occurrence of vertebral anomalies, anal atresia, cardiovascular malformations, tracheoesophageal fistula and/or esophageal atresia, renal anomalies, and/or limb anomalies, and is referred to by the first letters of its components. Studies investigating the clinical characteristics of VA patients and probing of the observed current six component types are limited, and none of them is focused on neonates. We investigated the clinical characteristics of our patients diagnosed as having VA in the newborn period. METHODS: We retrospectively reviewed the neonates whose final diagnosis was VACTERL association. Presence of at least three components of previously reported six anomalies was accepted as VACTERL association. Sex, birthweight, gestational age, postnatal age, anomalies of the systems that are included in VA, and the other features were recorded. RESULTS: There was a male predominance (14/11) of 28 patients; and there were three patients with ambiguous genitalia. The most common observed VACTERL component was vertebral anomalies (n= 26), followed by anal atresia (n= 19), tracheoesophageal fistula/esophageal atresia (n= 17), renal anomalies (n= 15), limb anomalies (n= 15) and cardiac anomalies (n= 14). The most frequent combination was VCTL (n= 4). Fifteen (57%) patients had non-VACTERL anomalies and the most frequent of these was ambiguous genitalia (n= 3). CONCLUSION: VA patients may have different clinical characteristics in different populations, and clinicians may miss some component features if the patients are evaluated after the neonatal period. PMID- 22300428 TI - Size and composition control of Pt-In nanoparticles prepared by seed-mediated growth using bimetallic seeds. AB - A two-step method has been developed for precise size and composition control of bimetallic Pt-In nanoparticles. Very small (1.62 nm) PtIn seed nanoparticles with 1:1 metal ratio were prepared in the absence of capping agents followed by growth of Pt on their surface in the presence of oleyl amine as reducing and stabilizing agent. Nanoparticles with bulk compositions of Pt(4)In, Pt(3)In, and Pt(2)In could be synthesized with average diameter smaller than 3 nm. TEM, EDX, and XPS provided evidence for homogeneous growth without separate nucleation of pure platinum nanoparticles in the reaction solution. Pt(3)In nanoparticles were deposited onto SiO(2) surface by incipient wetness impregnation. Temperature induced changes in the particle surface were monitored by in situ IR spectroscopy and CO adsorption. It was found that surface alloy composition of the particles could be tuned by using oxidizing or reducing atmospheres. PMID- 22300429 TI - LF immunomodulatory strategies: mastering bacterial endotoxin. AB - Lactoferrin (LF), an iron-binding glycoprotein expressed in most biological fluids, represents a major component of mammalian innate immune system. The multiple activities of LF rely not only on its capacity to bind iron but also to interact with molecular and cellular components of both the host and pathogens. LF can bind and sequester lipopolysaccharide thus preventing proinflammatory pathway activation, sepsis, and tissue damage. However, the interplay between LF and lipopolysaccharide is complex and may lead to different outcomes including both the suppression of inflammatory response and immune activation. Understanding the molecular basis and the functional consequences of this complex interaction is critically relevant in the development of LF-based therapeutic interventions in humans. PMID- 22300430 TI - Relationship between progression of visual field damage and choroidal thickness in eyes with normal-tension glaucoma. AB - BACKGROUND: To measure choroidal thickness in normal eyes and in patients with normal-tension glaucoma using enhanced depth imaging optical coherence tomography and evaluate the association between choroidal thickness and progression of visual field damage. DESIGN: Cross-sectional comparative study. PARTICIPANTS: A total of 62 eyes of 62 normal subjects and 45 eyes of 45 normal-tension glaucoma patients were examined. METHODS: The choroid was measured at the fovea and 3 mm nasal and temporal from the fovea. In the separate study, both eyes of the patients with normal-tension glaucoma were included in the analyses. Visual fields were measured with automated perimetry. Changes in mean deviation per year (dB/year), that is, mean deviation slope, were calculated. MAIN OUTCOME MEASURES: Difference in the choroidal thickness between the normal subjects and the patients with normal-tension glaucoma. The relationship between mean deviation slope and the choroidal thickness in eyes with normal-tension glaucoma was analysed. RESULTS: Compared with normal subjects, the choroidal thickness was significantly thinner in eyes with normal-tension glaucoma at 3 mm nasal from the fovea (P = 0.02). There was a significant correlation between the choroidal thickness at 3 mm nasal from the fovea and the mean deviation slope (Pearson's r = 0.413; P < 0.001). CONCLUSION: The decrease in the thickness of the choroid at 3 mm nasal from the fovea in eyes with normal-tension glaucoma may be associated with progressive visual field loss. Thus, choroidal abnormalities may play a role in the pathogenesis of normal-tension glaucoma. PMID- 22300431 TI - Three-year outcomes from BENEFIT-EXT: a phase III study of belatacept versus cyclosporine in recipients of extended criteria donor kidneys. AB - Recipients of extended-criteria donor (ECD) kidneys have poorer long-term outcomes compared to standard-criteria donor kidney recipients. We report 3-year outcomes from a randomized, phase III study in recipients of de novo ECD kidneys (n = 543) assigned (1:1:1) to either a more intensive (MI) or less intensive (LI) belatacept regimen, or cyclosporine. Three hundred twenty-three patients completed treatment by year 3. Patient survival with a functioning graft was comparable between groups (80% in MI, 82% in LI, 80% in cyclosporine). Mean calculated GFR (cGFR) was 11 mL/min higher in belatacept-treated versus cyclosporine-treated patients (42.7 in MI, 42.2 in LI, 31.5 mL/min in cyclosporine). More cyclosporine-treated patients (44%) progressed to GFR <30 mL/min (chronic kidney disease [CKD] stage 4/5) than belatacept-treated patients (27-30%). Acute rejection rates were similar between groups. Posttransplant lymphoproliferative disorder (PTLD) occurrence was higher in belatacept-treated patients (two in MI, three in LI), most of which occurred during the first 18 months; four additional cases (3 in LI, 1 in cyclosporine) occurred after 3 years. Tuberculosis was reported in two MI, four LI and no cyclosporine patients. In conclusion, at 3 years after transplantation, immunosuppression with belatacept resulted in similar patient survival, graft survival and acute rejection, with better renal function compared with cyclosporine. As previously reported, PTLD and tuberculosis were the principal safety findings associated with belatacept in this study population. PMID- 22300432 TI - Oxygen activation in neuronal NO synthase: resolving the consecutive mono oxygenation steps. AB - The vital signalling molecule NO is produced by mammalian NOS (nitric oxide synthase) enzymes in two steps. L-arginine is converted into NOHA (Nomega-hydroxy L-arginine), which is converted into NO and citrulline. Both steps are thought to proceed via similar mechanisms in which the cofactor BH4 (tetrahydrobiopterin) activates dioxygen at the haem site by electron transfer. The subsequent events are poorly understood due to the lack of stable intermediates. By analogy with cytochrome P450, a haem-iron oxo species may be formed, or direct reaction between a haem-peroxy intermediate and substrate may occur. The two steps may also occur via different mechanisms. In the present paper we analyse the two reaction steps using the G586S mutant of nNOS (neuronal NOS), which introduces an additional hydrogen bond in the active site and provides an additional proton source. In the mutant enzyme, BH4 activates dioxygen as in the wild-type enzyme, but an interesting intermediate haem species is then observed. This may be a stabilized form of the active oxygenating species. The mutant is able to perform step 2 (reaction with NOHA), but not step 1 (with L-arginine) indicating that the extra hydrogen bond enables it to discriminate between the two mono-oxygenation steps. This implies that the two steps follow different chemical mechanisms. PMID- 22300433 TI - Cough and dyspnoea may discriminate allergic and infectious respiratory phenotypes in infancy. AB - Asthma symptoms are non-specific during infancy, making the identification of different subgroups among preschool children with early respiratory manifestations an important challenge. We previously used a clustering approach to identify bronchial obstructive phenotypes in 1-yr-old infants from the Pollution and Asthma Risk: an Infant Study (PARIS) birth cohort. In the present study, we examined whether these phenotypes were stable at 3 yr and studied their comorbidity and risk factors. Partitioning around medoids (PAM) method was applied at 1 and 3 yr of age to cluster children according to wheezing, dry night cough, dyspnoea with sleep disturbance and breathlessness. The resulting groups were used to derive phenotypes in 2084 children during their first 3 yr of life. Analysis of associated comorbidity and risk factors was conducted using multinomial logistic regression. PAM groups were similarly defined at both ages so that two respiratory phenotypes were identified between birth and 3 yr: cough phenotype (CP) and dyspnoea phenotype (DP) including 14.1% and 30.7% of children, respectively. CP infants experienced more often allergic features than DP, dominated by respiratory infections. Parental history of allergy, potential allergen exposure and psychosocial factors were associated with CP. Day care centre attendance was more frequent in DP as well as exposure to domestic chemical pollution, suggesting a greater vulnerability to pathogens. Finally, dry night cough and dyspnoea disturbing the sleep appear to be markers of two respiratory profiles potentially allergic and infectious before 3 yr old. PMID- 22300434 TI - Soil sampling and isolation of extracellular DNA from large amount of starting material suitable for metabarcoding studies. AB - DNA metabarcoding refers to the DNA-based identification of multiple species from a single complex and degraded environmental sample. We developed new sampling and extraction protocols suitable for DNA metabarcoding analyses targeting soil extracellular DNA. The proposed sampling protocol has been designed to reduce, as much as possible, the influence of local heterogeneity by processing a large amount of soil resulting from the mixing of many different cores. The DNA extraction is based on the use of saturated phosphate buffer. The sampling and extraction protocols were validated first by analysing plant DNA from a set of 12 plots corresponding to four plant communities in alpine meadows, and, second, by conducting pilot experiments on fungi and earthworms. The results of the validation experiments clearly demonstrated that sound biological information can be retrieved when following these sampling and extraction procedures. Such a protocol can be implemented at any time of the year without any preliminary knowledge of specific types of organisms during the sampling. It offers the opportunity to analyse all groups of organisms using a single sampling/extraction procedure and opens the possibility to fully standardize biodiversity surveys. PMID- 22300436 TI - Ripened dairy products differentially affect hepatic lipid content and adipose tissue oxidative stress markers in obese and type 2 diabetic mice. AB - Growing evidence suggests that the consumption of dairy products may contribute to a reduced incidence of cardiovascular risk factors, such as obesity, dyslipidemia, and type 2 diabetes. The fatty acid composition in milk fat, the duration of ripening, and the complexity of the food matrices are important factors that may interfere with the physiological impact. In this study, we treated genetic obese and type 2 diabetic mice (db/db) for 4 weeks with different dairy (cheese-based) products, differing by the duration of ripening (0, 15, or 35 days). We found that 35 days ripened product significantly improved glucose tolerance, an effect associated with a decreased adipose tissue lipid peroxide markers (TBARS and NAPDH-oxidase mRNA expression), without affecting body weight, food intake, and fat mass. Both fermented matrices significantly decreased the hepatic lipid content, without modifying plasma triglycerides or plasma total cholesterol. These data suggest that dairy products issued from longer ripening positively impact glucose tolerance, hepatic steatosis, and adipose tissue oxidative stress. Further investigations are warranted to decipher the interactions between milk products fermentation, lipids, and host metabolism. PMID- 22300437 TI - Self-assembly of [M8L4] and [M4L2] fluorescent metallomacrocycles with carbazole based dipyrazole ligands. AB - Fluorescent carbazole-based dipyrazole ligands (H(2)L(1-4)) were employed to coordinate with dipalladium corners ([(phen)(2)Pd(2)(NO(3))(2)](NO(3))(2), [(dmbpy)(2)Pd(2)(NO(3))(2)](NO(3))(2), or [(15-crown-5 phen)(2)Pd(2)(NO(3))(2)](NO(3))(2), where phen = 1,10-phenanthroline and dmbpy = 4,4'-dimethyl-2,2'-bipyridine, in aqueous solution to afford a series of positively charged [M(8)L(4)](8+) or [M(4)L(2)](4+) multimetallomacrocycles with remarkable water solubility. Their structures were characterized by (1)H NMR spectroscopy, electrospray ionization mass spectrometry, and elemental analysis and in the cases of 1.8BF(4)(-) ([(phen)(8)Pd(8)L(1)(4)](BF(4))(8)), and 3.4BF(4)(-) ([(phen)(4)Pd(4)L(2)(2)](BF(4))(4)) by single-crystal X-ray diffraction analysis. Complexes 3-8 are square-type hybrid metallomacrocycles, while complexes 1 and 2 exhibit folding cyclic structures. Interestingly, in single-crystal structures of 1.8BF(4)(-) and 3.4BF(4)(-), BF(4)(-) anions are trapped in the dipalladium clips through anion-pi interaction. The luminescence properties and interaction toward anions of these metallomacrocycles were discussed. PMID- 22300438 TI - Conversion rates of abstracts presented at the Urological Society of Australia and New Zealand (USANZ) Annual Scientific Meeting into full-text journal articles. AB - What's known on the subject? and What does the study add? It is well known that the transition of a presented abstract in a scientific meeting to a journal article improves the quality of the meeting and prevents an abstract being incorporated into meta-analyses or practice guidelines without proper appraisal. This is the first analysis of USANZ Annual Scientific Meeting abstracts' conversion to full publication. With relatively low publication rates compared to other international meetings, this review identifies the need for mechanisms to encourage USANZ researchers to convert their abstracts into published articles. The numbers and characteristics of the abstracts presented at the Annual Scientific Meetings (ASM) of the Urological Society of Australia and New Zealand (USANZ) that are converted to peer-reviewed publications have not previously been analysed and published. We undertook a review of all abstracts presented at the USANZ ASM from 2005 to 2009. A PubMed search was performed between 15 June and 15 July 2012, using a search algorithm to identify the full-text publications of the presented abstracts. Correlation between abstract characteristics and publication rate was then examined to distinguish the predictors for publications. Of 614 abstracts that were presented at USANZ ASM between 2005 and 2009, 183 papers were published, giving a publication rate of 29.80%. The papers were predominantly published in urological journals and were more likely to be published if they were presented by an international author or were retrospective studies or if basic science research. The mean (SD) time to publication was 14.46 (13.89) months and the mean Impact Factor of journals where papers were published was 2.90. The overall publication rate was relatively low compared with other urological meetings held in America and Europe. USANZ has a challenge of encouraging higher-quality research from the authors to further enhance its publication rate and consequently the calibre of the meeting itself. PMID- 22300439 TI - The pharmacokinetics of oxypurinol in people with gout. AB - AIMS: Our aim was to identify and quantify the sources of variability in oxypurinol pharmacokinetics and explore relationships with plasma urate concentrations. METHODS: Non-linear mixed effects modelling was applied to concentration-time data from 155 gouty patients with demographic, medical history and renal transporter genotype information. RESULTS: A one compartment pharmacokinetic model with first order absorption best described the oxypurinol concentration-time data. Renal function and concomitant medicines (diuretics and probenecid), but not transporter genotype, significantly influenced oxypurinol pharmacokinetics and reduced the between subject variability in the apparent clearance of oxypurinol (CL/F(m)) from 65% to 29%. CL/F(m) for patients with normal, mild, moderate and severe renal impairment was 1.8, 0.6, 0.3 and 0.18 l h(-1), respectively. Model predictions showed a relationship between plasma oxypurinol and urate concentrations and failure to reach target oxypurinol concentrations using suggested allopurinol dosing guidelines. CONCLUSIONS: In conclusion, this first established pharmacokinetic model provides a tool to achieve target oxypurinol plasma concentrations, thereby optimizing the effectiveness and safety of allopurinol therapy in gouty patients with various degrees of renal impairment. PMID- 22300440 TI - Positive association of polymorphisms in estrogen biosynthesis gene, CYP19A1, and metabolism, GST, in breast cancer susceptibility. AB - PURPOSE: This case-control study was conducted in order to evaluate the potential role of polymorphic genes encoding enzymes involved in estrogen biosynthesis (CYP19A1) and metabolism (GSTM1, GSTT1, and GSTP1), and their action in modulating individual susceptibility to breast cancer. METHODS: Genomic DNA was extracted from blood samples of 101 patients with histological diagnosis of breast cancer and 121 healthy women. Genotyping analyses of CYP19A1 codon 39 Trp/Arg (T/C), GSTM1 and GSTT1 homozygous deletions, and GSTP1 codon 105 Ile/Val (A/G) were performed by polymerase chain reaction-based methods. RESULTS: Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by unconditional logistic regression. Significant statistical association of the TC/CC genotypes combined with breast cancer risk was found, with reference to TT genotype (OR=1.770; 95% CI=1.036-3.024; p=0.036). Also, CYP19A1 arginine allele in homozygosity or heterozygosity (TC/CC) was associated with a significant increased risk for breast cancer when associated to GSTM1 null genotype (OR=6.158; 95% CI=2.676-14.171; p<0.001) and GSTT1 null genotype (OR=4.870; 95% CI=2.216-10.700; p<0.001). The three-way combination of CYP19A1 TC/CC, GSTM1 null, and GSTT1 null polymorphism was related with significant increased risk for breast cancer (OR=11.429; 95% CI=3.590-36.385; p<0.001). Valine alleles compared with isoleucine alleles in codon 105 in GSTP1, in combination with CYP19A1 genotypes, were not associated with an increase of breast cancer development. CONCLUSIONS: Our results suggest that the effect of CYP19A1 T/C polymorphism in susceptibility to breast cancer development can be modulated by the presence of GSTM1 and GSTT1, but not GSTP1. PMID- 22300441 TI - Successful treatment of severe accidental hypothermia with cardiac arrest for a long time using cardiopulmonary bypass - report of a case. AB - Accidental hypothermia is defined as an unintentional decrease in body temperature to below 35 degrees C, and cases in which temperatures drop below 28 degrees C are considered severe and have a high mortality rate. This study presents the case of a 57-year-old man discovered drifting at sea who was admitted to our hospital suffering from cardiac arrest. Upon admittance, an electrocardiogram indicated asystole, and the patient's temperature was 22 degrees C. Thirty minutes of standard CPR and external rewarming were ineffective in raising his temperature. However, although he had been in cardiac arrest for nearly 2 h, it was decided to continue resuscitation, and a cardiopulmonary bypass (CPB) was initiated. CPB was successful in gradually rewarming the patient and restoring spontaneous circulation. After approximately 1 month of rehabilitation, the patient was subsequently discharged, displaying no neurological deficits. The successful recovery in this case suggests that CPB can be considered a useful way to treat severe hypothermia, particularly in those suffering from cardiac arrest. PMID- 22300442 TI - Mono-allelic retrotransposon insertion addresses epigenetic transcriptional repression in human genome. AB - BACKGROUND: Retrotransposons have been extensively studied in plants and animals and have been shown to have an impact on human genome dynamics and evolution. Their ability to move within genomes gives retrotransposons to affect genome instability. METHODS: we examined the polymorphic inserted AluYa5, evolutionary young Alu, in the progesterone receptor gene to determine the effects of Alu insertion on molecular environment. We used mono-allelic inserted cell lines which carry both Alu-present and Alu-absent alleles. To determine the epigenetic change and gene expression, we performed restriction enzyme digestion, Pyrosequencing, and Chromatin Immunoprecipitation. RESULTS: We observed that the polymorphic insertion of evolutionally young Alu causes increasing levels of DNA methylation in the surrounding genomic area and generates inactive histone tail modifications. Consequently the Alu insertion deleteriously inactivates the neighboring gene expression. CONCLUSION: The mono-allelic Alu insertion cell line clearly showed that polymorphic inserted repetitive elements cause the inactivation of neighboring gene expression, bringing aberrant epigenetic changes. PMID- 22300443 TI - Long-term outcomes of psychodynamic residential treatment for severely disturbed young adults: a naturalistic study at a Swedish therapeutic community. AB - AIMS: This study examined the long-term effectiveness of a treatment model at a Swedish therapeutic community for young adults with severe personality disorders, combining milieu therapy and inpatient long-term psychodynamic psychotherapy. METHODS: Data were collected for the 56 residents between 1994 and 2008 at intake, termination and 2-year follow-up. Patient residency ranged from 2 to 60 months, with average psychotherapy duration of 30 months. Self-rated outcome was measured using the Symptom Checklist-90-R. Expert-rated outcomes comprised the Global Assessment of Functioning, the Strauss-Carpenter Outcome Scale and the Integration/Sealing-over Scale. A series of mixed-model analyses of variance with one fixed factor (time) was performed to examine the outcomes for the total sample of completers. Effect sizes for within-group change and percentages of improved, unchanged and deteriorated patients were calculated for patients participating in the data collection on all three time points. RESULTS: All outcome measures showed significant improvement on a group level from intake to discharge. Most patients had maintained the therapeutic gains at the 2-year follow-up. The effect sizes were high and the Reliable Change Index provided evidence of good outcome for 92% of the patients at follow-up. The expert ratings gave somewhat larger effect sizes than the patients' self-ratings. CONCLUSIONS: The effect sizes and success rates are at a comparable level with corresponding studies of long-term treatments of personality disorders. Most patients had a substantial individual improvement from intake to termination and follow-up. This indicates the effectiveness of this highly specialized and intensive treatment approach for severely disturbed young adult patients. PMID- 22300444 TI - Magnetoelectric charge trap memory. AB - It is demonstrated that a charge-trapping layer placed in proximity to a ferromagnetic metal enables efficient electrical and optical control of the metal's magnetic properties. Retention of charge trapped inside the charge trapping layer provides nonvolatility to the magnetoelectric effect and enhances its efficiency by an order of magnitude. As such, an engineered charge-trapping layer can be used to realize the magnetoelectric equivalent to today's pervasive charge trap flash memory technology. Moreover, by supplying trapped charges optically instead of electrically, a focused laser beam can be used to imprint the magnetic state into a continuous metal film. PMID- 22300445 TI - Multiple hyperacute rejections in the absence of detectable complement activation in a patient with endothelial cell reactive antibody. AB - This case involves a 54-year-old patient with polycystic kidney disease and a history of hyperacute allograft rejections. Two previous compatible live donor transplants functioned immediately but failed within the first 12 h due to antibody-injury. This patient was referred for a third transplant due to decreased vascular access and progressive hypotension from uremic autonomic dysfunction. He was broadly sensitized to HLA; however, a live donor was identified through kidney paired donation for whom he had no donor-specific HLA antibody (HLA-DSA). This patient received one plasmapheresis (PP) and intravenous immunoglobulin (IVIg) treatment, anti-CD25, and anti-CD20 antibodies prior to transplant. The allograft functioned immediately but became anuric within 24 h. A biopsy revealed antibody-mediated injury in the absence of C4d. Daily PP/IVIg, a second dose of anti-CD20, and eculizumab were administered. A retrospective endothelial cell crossmatch (ECXM) was positive with serum drawn 3 days prior to transplant and these EC antibodies were enriched for IgG2 and IgG4, noncomplement activating subclasses. Postoperative day (POD) 3, HLA-DSA remained negative but a rescue splenectomy was performed. Cultured splenocytes produced antibodies that bound donor ECs but not lymphocytes. Bortezomib was initiated on POD5. Despite aggressive therapy, the allograft never regained function. PMID- 22300447 TI - Physical, social and societal functioning of children with congenital adrenal hyperplasia (CAH) and their parents, in a Dutch population. AB - BACKGROUND: Most research concerning congenital adrenal hyperplasia (CAH) and related conditions caused by primary adrenal insufficiency, such as Addison's or Cushing's disease, has focused on medical aspects rather than on patients' quality of life. Therefore, our objective was to investigate the physical, social and societal functioning of children with CAH and their parents in a Dutch population. METHODS: The study is descriptive and cross-sectional. Self-designed questionnaires, based on questionnaires developed in the Netherlands for different patient groups, were sent to parents of children with CAH between 0 and 18 years old. Participants were recruited through the Dutch patient group for Adrenal Disease (NVACP) and six hospitals in the Netherlands. Three different questionnaires were designed for parents: for children aged 0 - 4, aged 4 - 12 and aged 12 - 18. Additionally, a fourth questionnaire was sent to adolescents with CAH aged 12 - 18. Main outcome measures were experienced burden of the condition, self-management and participation in several areas, such as school and leisure time. RESULTS: A total of 106 parents returned the questionnaire, 12 regarding pre-school children (0-4 years), 63 regarding primary school children (4-12 years), and 32 regarding secondary school children (12-18 years), combined response rate 69.7%. Also, 24 adolescents returned the questionnaire. Children and adolescents with CAH appear to be capable of self-management at a young age. Experienced burden of the condition is low, although children experience several health related problems on a daily basis. Children participate well in school and leisure time. Few children carry a crisis card or emergency injection with them. CONCLUSIONS: Overall, our research shows that, according to their parents, children with CAH experience few negative effects of the condition and that they participate well in several areas such as school and leisure time. However, improvements can be made concerning the measures parents and children must take to prevent an adrenal crisis. PMID- 22300446 TI - Cocaine decreases expression of neurogranin via alterations in thyroid receptor/retinoid X receptor signaling. AB - Mounting evidence suggests a potential link between cocaine abuse, disruptions in hypothalamic-pituitary-thyroid axis signaling, and neuroplasticity, but molecular mechanisms remain unknown. Neurogranin (Ng) is a gene containing a thyroid hormone-responsive element within its first intron that is involved in synaptic plasticity. Transcriptional activation requires heterodimerization of thyroid hormone receptor (TR) and retinoid X receptor (RXR) bound by their respective ligands, tri-iodothryonine and 9-cis-retinoic acid (9-cis-RA), and subsequent binding of this complex to the thyroid hormone-responsive element of the Ng gene. In this study, the effects of chronic cocaine abuse on Ng expression in euthyroid and hypothyroid mice were assessed. In cocaine-treated mice, decreased Ng expression was observed in the absence of changes in levels of thyroid hormones or other hypothalamic-pituitary-thyroid signaling factors. Therefore, we hypothesized that cocaine decreases Ng expression via alterations in 9-cis-RA availability and TR/RXR signaling. In support of this hypothesis, RXR-gamma was significantly decreased in brains of cocaine-treated mice while CYP26A1, the main enzyme responsible for neuronal RA degradation, was significantly increased. Results from this study provide the first evidence for a direct effect of cocaine abuse on TR/RXR signaling, RA metabolism, and transcriptional regulation of Ng, a gene essential for adult neuroplasticity. PMID- 22300448 TI - Tracheal colonization in preterm infants supported with nasal continuous positive airway pressure. AB - BACKGROUND: The aim of this study was to examine endotracheal bacteriological status in premature infants who are supported by nasal continuous positive airway pressure (CPAP) without any history of tracheal intubation. METHODS: In this prospective study, we enrolled 60 premature infants with respiratory distress; of these, 30 were supported by CPAP without tracheal intubation, and 30 were intubated and mechanically ventilated. Infants were enrolled at a postnatal age of < 24 h. Endotracheal (ET) cultures were taken at 24 h and at the 5th day of life. In the CPAP group, a suction catheter was sterilely inserted into the trachea while directly visualizing the vocal cords using a laryngoscope. RESULTS: ET cultures taken on the 1st day of life showed colonization in 7/30 (23%) in the CPAP group versus 19/30 (63%) in the mechanically ventilated group (P= 0.002). Tracheal cultures on day 5 were positive in 5/30 (17%) and 11/30 (37%), respectively (P= 0.093). Klebsiella ssp. represented the most frequently isolated organism in both groups. A positive tracheal culture at 5 days was associated with a longer duration of respiratory support in the CPAP group (P= 0.05) but not in the ventilation group. Endotracheal culture at 5 days was associated with mortality in the ventilation group (8/11 vs 5/19, P= 0.02), but not in the CPAP group (1/5 vs 2/25, P= 0.45). Early endotracheal cultures did not relate with mortality in either of the groups. CONCLUSION: The trachea of premature infants supported with CPAP is at risk for bacterial colonization. Predisposing factors, mechanisms and clinical implications of these novel findings need to be studied. PMID- 22300449 TI - Soft tissue structures resisting anterior instability in a computational glenohumeral joint model. AB - The glenohumeral joint is the most dislocated joint in the body due to the lack of bony constraints and the dependence on soft tissue for stability. The roles that various structures provide to joint function are important for understanding injury treatment and orthopaedic device design purposes. The goal of this study was to develop a computational model of the glenohumeral joint whereby joint behaviour was dictated by articular contact, ligamentous constraints, muscle loading and external perturbations. The bone structure of the computational model consisted of assembled computer tomographic images of the scapula, humerus and clavicle. The soft tissue elements were composed of forces and tension-only springs that represented muscles and ligaments. Validation of this model was achieved by comparing computational predictions to the results of a cadaveric experiment in which the relative contribution of muscles and ligaments to anterior joint stability was examined. The computational model predicted an anterior subluxation force that was similar to the cadaveric experimental results in humeral external rotation. The individual structure results showed the subscapularis to be critical to stabilisation in both neutral and external rotations, the biceps stabilised the joint in neutral but not in external rotation, and the inferior glenohumeral ligament resisted anterior displacement only in external rotation. The model's predictions were similar to the conclusions of the cadaveric experiment and the literature. Knowledge gained from this type of model could assist in further understanding the contribution of soft tissue stabilisers to joint function, pre-operative planning or the design of orthopaedic implants. PMID- 22300450 TI - A molecular diffusion based utility model for Drosophila larval phototaxis. AB - BACKGROUND: Generally, utility based decision making models focus on experimental outcomes. In this paper we propose a utility model based on molecular diffusion to simulate the choice behavior of Drosophila larvae exposed to different light conditions. METHODS: In this paper, light/dark choice-based Drosophila larval phototaxis is analyzed with our molecular diffusion based model. An ISCEM algorithm is developed to estimate the model parameters. RESULTS: By applying this behavioral utility model to light intensity and phototaxis data, we show that this model fits the experimental data very well. CONCLUSIONS: Our model provides new insights into decision making mechanisms in general. From an engineering viewpoint, we propose that the model could be applied to a wider range of decision making practices. PMID- 22300451 TI - Self-assembled, nanostructured polypyrrole films grown in a high-gravity environment. AB - A simple, novel method of synthesizing self-assembled, nanostructured conducting polymer films has been developed. Applying an increased centrifugal force on the electrodes during the electrochemical deposition process yields high surface area, micro- or nanostructured polymer films. Scanning electron microscopy showed that as the applied g-force increased, the polymers progressed from having smooth, "cauliflower" morphologies, to intermediate microstructured surfaces, to finally dense nanostructured surfaces with pore sizes as small as 50 nm. Cyclic voltammetry revealed that films grown at higher centrifugal accelerations (higher than 500g) exhibited less degradation after electrochemical cycling and more capacitive behavior. PMID- 22300452 TI - Prescribing patterns of low doses of antipsychotic medications in older Asian patients with schizophrenia, 2001-2009. AB - BACKGROUND: This study examined the use of low doses of antipsychotic medications (300 mg/day CPZeq or less) in older Asian patients with schizophrenia and its demographic and clinical correlates. METHODS: Information on hospitalized patients with schizophrenia, aged 55 years or older, was extracted from the database of the Research on Asian Psychotropic Prescription Patterns (REAP) study (2001-2009). Data on 1,452 patients in eight Asian countries and territories including China, Hong Kong, Japan, Korea, Singapore, Taiwan, India, and Malaysia were analyzed. Sociodemographic and clinical characteristics and antipsychotic prescriptions were recorded using a standardized protocol and data collection procedure. RESULTS: The prescription frequency for low doses of antipsychotic medications was 40.9% in the pooled sample. Multiple logistic regression analysis of the whole sample showed that patients on low doses of antipsychotic medications were more likely to be female, have an older age, a shorter length of illness, and less positive symptoms. Of patients in the six countries and territories that participated in all the surveys between 2001 and 2009, those in Japan were less likely to receive low doses of antipsychotics. CONCLUSION: Low doses of antipsychotic medications were only applied in less than half of older Asian patients with schizophrenia. PMID- 22300453 TI - CobB1 deacetylase activity in Streptomyces coelicolor. AB - Silent information regulators are NAD(+)-dependent enzymes that display differential specificity toward acetylated substrates. This report provides first evidence for deacetylation activity of CobB1 in Streptomyces coelicolor. The protein is highly conserved in streptomycetes. The CobB1 protein catalytically removes the acetyl group from acetylated bovine serum albumin. In the absence of NAD+ or when NAD+ was substituted with nicotinamide, deacetylation was stopped. We isolated gene encoding AcetylCoA synthetaseA. The recombinant enzyme produces Acetyl-CoA from acetate. The highest acsA-mRNA level was detected in cells from the exponential phase of growth, and then decreased in transition and stationary phases of growth. Acetylated acsA loses the ability to transfer acetate to CoA. Deacetylation of the enzyme required CobB1, ATP-Mg2, and NAD+. Using specific antibodies against acetylated lys, CobB1, and acsA, we found relationship between level of CobB1 and acetylation of acsA, indicating that CobB1 is involved in regulating the acetylation level of acsA and consequently its activity. It was found that 1-acetyl-tetrahydroxy and 1-acetyl pentahydroxy antraquinone inhibit the deacetylation activity of CobB1. PMID- 22300454 TI - Singapore Malay Eye Study: rationale and methodology of 6-year follow-up study (SiMES-2). AB - BACKGROUND: To describe the rationale and study design of a follow-up epidemiological eye study among Singaporean Malay adults. DESIGN: Follow-up prospective population-based study. PARTICIPANTS: Participants of the Singapore Malay Eye Study (SiMES-1), which was conducted from August 2004 to June 2006. METHODS: This is a follow-up study of the 3280 participants who participated in the SiMES-1 and are residing in Singapore. All participants of this follow-up study will undergo various standardized validated questionnaires on socio demographics, quality of life and impact of visual impairment. Participants will undergo assessment of blood pressure, anthropometry, presenting and best corrected visual acuity, subjective refraction, ocular biometry, slit lamp and dilated eye examination, Goldmann tonometry, optic disc imaging, digital lens and retinal photography. Retinal tomography, retinal optical coherence topography and fundus autofluorescence will also be performed. Gonioscopy and visual fields examination will be performed on selected individuals. MAIN OUTCOME MEASURES: Incidence, risk factors and impact of visual impairment and major eye diseases. RESULTS: A total of 3280 people who participated in the SiMES-1 will be contacted and invited to participate in this follow-up study. It is estimated that 12.8% of the participants will be deceased and there will be an 80% participation rate for the survivors of SiMES-1 (approximately 2288 participants). CONCLUSION: SiMES-2 will be one of the few follow-up epidemiological eye studies among Asians and will determine the cumulative 6-year incidence, progression, risk factors and impact of major eye diseases in Singaporean Malay adults. PMID- 22300455 TI - Direct experimental evidence that early-life farm environment influences regulation of immune responses. AB - BACKGROUND: In mammals, early-life environmental variations appear to affect microbial colonization and therefore competent immune development, and exposure to farm environments in infants has been inversely correlated with allergy development. Modelling these effects using manipulation of neonatal rodents is difficult due to their dependency on the mother, but the relatively independent piglet is increasingly identified as a valuable translational model for humans. This study was designed to correlate immune regulation in piglets with early-life environment. METHODS: Piglets were nursed by their mother on a commercial farm, while isolator-reared siblings were formula fed. Fluorescence immunohistology was used to quantify T-reg and effector T-cell populations in the intestinal lamina propria and the systemic response to food proteins was quantified by capture ELISA. RESULTS: There was more CD4(+) and CD4(+) CD25(+) effector T-cell staining in the intestinal mucosa of the isolator-reared piglets compared with their farm-reared counterparts. In contrast, these isolator-reared piglets had a significantly reduced CD4(+) CD25(+) Foxp3(+) regulatory T-cell population compared to farm-reared littermates, resulting in a significantly higher T-reg-to effector ratio in the farm animals. Consistent with these findings, isolator reared piglets had an increased serum IgG anti-soya response to novel dietary soya protein relative to farm-reared piglets. CONCLUSION: Here, we provide the first direct evidence, derived from intervention, that components of the early life environment present on farms profoundly affects both local development of regulatory components of the mucosal immune system and immune responses to food proteins at weaning. We propose that neonatal piglets provide a tractable model which allows maternal and treatment effects to be statistically separated. PMID- 22300457 TI - Sirolimus conversion for renal dysfunction in liver transplant recipients: the devil really is in the details.... PMID- 22300456 TI - The co-occurring use and misuse of cannabis and tobacco: a review. AB - AIMS: Cannabis and tobacco use and misuse frequently co-occur. This review examines the epidemiological evidence supporting the life-time co-occurrence of cannabis and tobacco use and outlines the mechanisms that link these drugs to each other. Mechanisms include (i) shared genetic factors; (ii) shared environmental influences, including (iii) route of administration (via smoking), (iv) co-administration and (v) models of co-use. We also discuss respiratory harms associated with co-use of cannabis and tobacco, overlapping withdrawal syndromes and outline treatment implications for co-occurring use. METHODS: Selective review of published studies. RESULTS: Both cannabis and tobacco use and misuse are influenced by genetic factors, and a proportion of these genetic factors influence both cannabis and tobacco use and misuse. Environmental factors such as availability play an important role, with economic models suggesting a complementary relationship where increases in price of one drug decrease the use of the other. Route of administration and smoking cues may contribute to their sustained use. Similar withdrawal syndromes, with many symptoms in common, may have important treatment implications. Emerging evidence suggests that dual abstinence may predict better cessation outcomes, yet empirically researched treatments tailored for co-occurring use are lacking. CONCLUSIONS: There is accumulating evidence that some mechanisms linking cannabis and tobacco use are distinct from those contributing to co-occurring use of drugs in general. There is an urgent need for research to identify the underlying mechanisms and harness their potential etiological implications to tailor treatment options for this serious public health challenge. PMID- 22300458 TI - Insulin use is not significantly predictive for prostate cancer mortality in diabetic patients: a 12-year follow-up study. AB - What's known on the subject? and What does the study add? Even though a lower risk of prostate cancer has been reported in patients with diabetes, they may have a higher risk of cancer development involving the liver, pancreas, endometrium, colorectum, breast and bladder. Insulin may have mitogenic properties besides its metabolic function. However, whether exogenous insulin use for glycaemic control in diabetic patients could increase the risk of prostate cancer has rarely been studied. This is the first prospective follow-up study for up to 12 years to show that exogenous insulin use for glycaemic control in the diabetic patients is not significantly predictive for prostate cancer mortality. OBJECTIVE: To evaluate whether insulin use in diabetic patients could be predictive for prostate cancer mortality. PATIENTS AND METHODS: A total of 39 135 diabetic men aged >=40 years from a nationally representative cohort were followed prospectively from 1995 to 2006 for prostate cancer mortality. Cox proportional hazards models were used to estimate the hazard ratios for the following independent variables: age, diabetes type, diabetes duration, body mass index, smoking, insulin use and area of residence. The models were created for patients aged >=40 years and >=65 years, separately; and before and after excluding patients with a duration between onset of diabetes and prostate cancer mortality <5 years. RESULTS: A total of 105 diabetic men died of prostate cancer during follow-up. Age was the only significant risk factor. Insulin use was associated with an insignificantly higher risk of prostate cancer mortality ranging from 24% to 49%. When stratified by the duration of insulin use <5 and >=5 years, a lack of significant association was also observed. CONCLUSIONS: Insulin use in diabetic patients does not significantly predict the mortality from prostate cancer. Further confirmation in other ethnicities is needed. PMID- 22300459 TI - Management of bacterial infections in cirrhosis. AB - Bacterial infections are very frequent in advanced cirrhosis and become the first cause of death of these patients. Despite numerous experimental data and significant advances in the understanding of the pathogenesis of sepsis in cirrhosis, the outcome remains poor. Classical diagnostic parameters such as C reactive protein and SIRS criteria have less diagnostic capacity in the cirrhotic population, often delaying the diagnosis and the management of bacterial infection. Prompt and appropriate empirical antibiotic treatment of infection and early resuscitation of patients with severe sepsis or septic shock are essential in determining patient's outcome. A strategy of careful restriction of prophylactic antibiotics to the high-risk populations could reduce the spread of multidrug resistant bacteria. This review is focused on the currently recommended diagnostic, therapeutic and prophylactic strategies for bacterial infections in the cirrhotic population. PMID- 22300460 TI - Trends in liver transplantation 2011. AB - This review will highlight some of the important recent trends in liver transplantation. When possible, we will compare and contrast these trends across various regions of the world, in an effort to improve global consensus and better recognition of emerging data. PMID- 22300461 TI - Management of treatment failure in chronic hepatitis B. AB - Antiviral therapy of chronic hepatitis B remains a clinical challenge. The primary goal of therapy is to prevent liver disease progression. Because of the mechanism of viral persistence in infected hepatocytes, long-term antiviral therapy is needed in the majority of patients. Incomplete viral suppression and emergence of drug resistance is a major concern. The correct choice of a first line potent therapy to achieve sustained long-term suppression of viral replication provides the best chance of preventing treatment failure and drug resistance. Clinical studies have demonstrated that drugs with a high barrier to resistance, such as entecavir and tenofovir, have significantly lower rates of resistance when compared with those with a low barrier to resistance such as lamivudine, adefovir, or telbivudine. Management of treatment failure requires a precise clinical and accurate virologic monitoring as well as an early treatment intervention with appropriate complementary drugs with respect to their cross resistance profile. Long-term surveillance for treatment efficacy and possible emergence of drug resistance is necessary for those patients who have been sequentially treated with multiple antivirals. Finally, the identification of novel treatment targets remains a major research challenge to improve the efficacy of current antiviral therapy. PMID- 22300462 TI - Management of critically-ill cirrhotic patients. AB - Cirrhotic patients are prone to develop life-threatening complications that require emergency care and ICU admission. They can present specific decompensations related to cirrhosis such as variceal bleeding and hepatorenal syndrome (HRS) or other critical events also observed in the general population such as severe sepsis or septic shock. Clinical management of all these entities requires a specific approach in cirrhosis. Cirrhotic patients have a hyperdynamic circulation with high cardiac output and low systemic vascular resistance in the absence of infection. Circulatory dysfunction increases the susceptibility of critically-ill cirrhotic patients to develop multiple organ failure and attenuates vascular reactivity to vasopressor drugs. HRS, a severe functional renal failure occurring in patients with advanced cirrhosis and ascites, is also secondary to this circulatory dysfunction that leads to an extreme renal vasoconstriction. Moreover, hypotensive cirrhotic patients require a carefully balanced replacement of volemia, since overtransfusion increases portal hypertension and the risk of variceal bleeding and undertransfusion causes tissue hypoperfusion which increases the risk of multiple organ failure. Cirrhotic patients are also at a high risk for development of other bleeding complications and are more susceptible to nosocomial infections. This extreme complexity of critically-ill cirrhotic patients requires a specific medical approach that should be known by general intensivists since it has a negative impact on patient prognosis. This review will focus on the diagnostic approach and treatment strategies currently recommended in the critical care management of patients with cirrhosis. PMID- 22300463 TI - Management of hepatic vascular diseases. AB - Primary damage to hepatic vessels is rare. (i) Hepatic arterial disorders, related mostly to iatrogenic injury and occasionally to systemic diseases, lead to ischemic cholangiopathy. (ii) Hepatic vein or inferior vena cava thrombosis, causing primary Budd-Chiari syndrome, is related typically to a combination of underlying prothrombotic conditions, particularly myeloproliferative neoplasms, factor V Leiden, and oral contraceptive use. The outcome of Budd-Chiari syndrome has markedly improved with anticoagulation therapy and, when needed, angioplasty, stenting, TIPS, or liver transplantation. (iii) Extrahepatic portal vein thrombosis is related to local causes (advanced cirrhosis, surgery, malignant or inflammatory conditions), or general prothrombotic conditions (mostly myeloproliferative neoplasms or factor II gene mutation), often in combination. Anticoagulation at the early stage prevents thrombus extension and, in 40% of the cases, allows for recanalization. At the late stage, gastrointestinal bleeding related to portal hypertension can be prevented in the same way as in cirrhosis. (iv) Sinusoidal obstruction syndrome (or venoocclusive disease), caused by agents toxic to bone marrow progenitors and to sinusoidal endothelial cells, induces portal hypertension and liver dysfunction. Decreasing the intensity of myeloablative regimens reduces the incidence of sinusoidal toxicity. (v) Obstruction of intrahepatic portal veins (obliterative portal venopathy) can be associated with autoimmune diseases, prothrombotic conditions, or HIV infection. The disease can eventually be complicated with end-stage liver disease. Extrahepatic portal vein obstruction is common. Anticoagulation should be considered. (vi) Nodular regenerative hyperplasia is induced by the uneven perfusion due to obstructed sinusoids, or portal or hepatic venules. It causes pure portal hypertension. PMID- 22300464 TI - Management of alcoholic hepatitis. PMID- 22300465 TI - Managing systemic symptoms in chronic liver disease. AB - Improved medical management and the changing disease demographic mean that the majority of patients with chronic liver disease are living with the disease rather than dying from it. Historically, the perception has been that the impact of chronic liver disease is related entirely to the consequences of endstage liver disease; however, more recently a number of systemic symptoms have been recognised that can occur at any point in the natural history of chronic liver disease and which can be associated with functional impairment and reduced quality of life. The most characteristic of these systemic symptoms is fatigue, which frequently associates with sleep disturbance and autonomic dysfunction, particularly manifest as abnormality of blood pressure regulation. Cognitive symptoms can occur even in non-cirrhotic patients. Falls can present in patients with autonomic dysfunction, complicated by the presence of peripheral muscle strength problems. Importantly for clinicians managing chronic liver disease, the severity of these systemic symptoms is typically not related to liver disease severity, and therefore despite optimal liver disease management, patients can often continue to experience debilitating symptoms. The similarity in systemic symptoms between different chronic liver diseases (and indeed chronic inflammatory conditions affecting other organs) suggests the possibility of shared pathogenetic processes and raises the possibility of common management strategies, although further research is urgently needed to confirm this. In primary biliary cirrhosis, where our understanding of systemic symptoms is arguably most developed, structured management strategies have been shown to improve the quality of life of patients. It is highly likely that similar approaches will have comparable benefits for other chronic liver disease groups. Here, we review the current understanding of systemic symptoms in chronic liver disease and offer recommendations regarding the successful management of these symptoms. Critical for successful treatment is use of a structured and systematic approach to management in which all contributing factors are addressed in an organised fashion. We believe that such a systematic approach, when applied to research as well as to clinical management, will allow us to reduce the overall burden of chronic liver disease, improve quality of life and enhance functional ability. PMID- 22300466 TI - The interaction of metabolic factors with HCV infection: does it matter? AB - Given the pandemic spread of the hepatitis C virus (HCV) infection and the metabolic syndrome (MS), the burden of their interaction is a major public health issue, bound to increase in the near term. A better appreciation of the clinical consequences of the relationship between HCV and MS is needed, not only due to their potential synergism on liver disease severity, but also because of the multifaceted interactions between HCV and glucose and lipid metabolism. HCV infection per se does not carry an increased risk of MS, but is able to perturb glucose homeostasis through several direct and indirect mechanisms, leading to both hepatic and extrahepatic insulin resistance. This translates into accelerated liver disease progression (including the development of hepatocellular carcinoma), reduced response to antivirals and, in susceptible individuals, increased risk of developing full-blown type 2 diabetes. HCV may also cause hepatic steatosis, especially in patients infected with genotype 3, although the clinical impact of viral steatosis is debated. Possibly as a result of HCV-induced insulin resistance, and despite a paradoxically favourable lipid profile, the cardiovascular risk is moderately increased in chronic hepatitis C. In addition, the interaction with the MS further increases the risks of cirrhosis, hepatocellular carcinoma, diabetes, and cardiovascular events. Thus, targeted lifestyle and pharmacological measures are urgently warranted in chronic hepatitis C with metabolic alterations. PMID- 22300467 TI - Anti-fibrotic therapy: lost in translation? AB - While preclinical development of potential anti-fibrotics is far advanced, with numerous pharmacological targets and promising agents, almost none has entered clinical validation. Reasons are manifold, including the usually slow progression of liver fibrosis, requiring high numbers of well-stratified patients undergoing long-term treatment when conventional liver biopsy based parameters or hard liver related endpoints are used. Importantly, there is a notorious lack of sensitive and specific surrogate markers or imaging technologies for liver fibrosis progression or regression that would permit a rapid clinical screening for potential anti-fibrotics. Nonetheless, in view of an urgent need for anti fibrotics that positively impact morbidity and mortality from chronic liver diseases, the field is now moving more quickly towards clinical translation. This development is driven by thoughtful preclinical validation, a better study design and improved surrogate readouts using currently available methodologies. Moreover, upcoming novel biomarkers and imaging technologies will soon permit a more exact and efficient assessment of fibrosis progression and regression. PMID- 22300468 TI - Management of HCC. AB - Hepatocellular carcinoma (HCC) is a highly prevalent and lethal neoplasia, the management of which has significantly improved during the last few years. A better knowledge of the natural history of the tumor and the development of staging systems that stratify patients according to the characteristics of the tumor, the liver disease, and the performance status, such as the BCLC (Barcelona Clinic Liver Cancer) system, have led to a better prediction of prognosis and to a most appropriate treatment approach. Today curative therapies (resection, transplantation, ablation) can improve survival in patients diagnosed at an early HCC stage and offer a potential long-term cure. Patients with intermediate stage HCC benefit from chemoembolization and those diagnosed at advanced stage benefit from sorafenib, a multikinase inhibitor with antiangiogenic and antiproliferative effects. In this article we review the current management in HCC and the new advances in this field. PMID- 22300469 TI - Antiviral strategies in hepatitis C virus infection. AB - Resolution of the three-dimensional structures of several hepatitis C virus (HCV) proteins, together with the development of replicative cell culture systems, has led to the identification of a number of potential targets for direct-acting antiviral (DAA) agents. Numerous families of drugs that potently inhibit the HCV lifecycle in vitro have been identified, and some of these molecules have reached early to late clinical development. Two NS3/4A protease inhibitors, telaprevir and boceprevir, were approved in Europe and the United States in 2011 in combination with pegylated interferon (IFN)-alpha and ribavirin for the treatment of chronic hepatitis C related to HCV genotype 1, in both treatment-naive and treatment-experienced patients. Sustained virological response rates in the range of 6675% and 5966% (2988% if the response to the first course of therapy is taken into account) have been achieved in these two patient populations, respectively, with treatment durations of 24 to 48 weeks. A number of other DAAs are at the clinical developmental stage in combination with pegylated IFN-alpha and ribavirin or with other DAAs in IFN-free regimens, with or without ribavirin. They include second-wave, first-generation, and second-generation NS3/4A protease inhibitors, nucleoside/nucleotide analogue inhibitors and non-nucleoside inhibitorsof HCVRNA-dependent RNA polymerase, inhibitors of nonstructural protein 5A (NS5A) and host-targeted compounds, such as cyclophilin inhibitors and silibinin. The proof of concept that IFN-free regimens may lead to HCV eradication has recently been brought. However, new drugs may be associated with troublesome side effects and drugdrug interactions, and the ideal IFN-free DAA combination remains to be found. PMID- 22300470 TI - Disease progress and response to treatment as predictors of survival, disability, cognitive impairment and depression in Parkinson's disease. AB - AIM: To describe the time to clinical events (death, disability, cognitive impairment and depression) in Parkinson's disease using the time course of disease status and treatment as explanatory variables. METHODS: Disease status based on the Unified Parkinson's Disease Rating Scale (UPDRS) and the time to clinical outcome events were obtained from 800 patients who initially had early Parkinson's disease. Parametric hazard models were used to describe the time to the events of interest. RESULTS: Time course of disease status (severity) was an important predictor of clinical outcome events. There was an increased hazard ratio for death 1.4 (95% CI 1.31, 149), disability 2.75 (95% CI 2.30, 3.28), cognitive impairment 4.35 (95% CI 1.94, 9.74), and depressive state 1.43 (95% CI 1.26, 1.63) with each 10 unit increase of UPDRS. Age at study entry increased the hazard with hazard ratios of 49.1 (95% CI 8.7, 278) for death, 4.76 (95% CI 1.10, 20.6) for disability and 90.0 (95% CI 63.3-128) for cognitive impairment at age 60 years. Selegiline treatment had independent effects as a predictor of death at 8 year follow-up with a hazard ratio of 2.54 (95% CI 1.51, 4.25) but had beneficial effects on disability with a hazard ratio of 0.363 (95% CI 0.132, 0.533) and depression with a hazard ratio of 0.372 (95% CI 0.12, 0.552). CONCLUSIONS: Our findings show that the time course of disease status based on UPDRS is a much better predictor of future clinical events than any baseline disease characteristic. Continued selegiline treatment appears to increase the hazard of death. PMID- 22300471 TI - PCI-32765: a novel Bruton's tyrosine kinase inhibitor for the treatment of lymphoid malignancies. AB - INTRODUCTION: There has been a significant paradigm shift in the manner in which lymphoid malignancies are treated and managed. Treatment has been moving away from conventional chemotherapy and towards targeted therapy. The success of new classes of agents such as monoclonal antibodies, proteasome inhibitors and immunomodulatory derivatives has sparked further searches for novel pathways to inhibit. The Bruton's tyrosine kinase (Btk) pathway is a downstream mediator of the B-cell receptor (BCR) pathway, which is crucial in B-cell production and maintenance, and a potential therapeutic target. AREAS COVERED: This review will summarize the current knowledge of the Btk pathway and its role in lymphoid malignancies. It will also discuss the present data about PCI-32765 in both the preclinical and clinical setting. EXPERT OPINION: PCI-32765 is an oral irreversible Btk inhibitor with high potency and both preclinical and clinical activity in chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL). Phase I studies have demonstrated that it is well tolerated and has an excellent safety profile. Further studies are ongoing as a single agent and in combination with other targeted and conventional therapies. PCI-32765 is a very promising targeted therapy, and the data from these trials will ultimately decide its future role and success. PMID- 22300472 TI - An experimental protocol for mimicking pathomechanisms of traumatic brain injury in mice. AB - Traumatic brain injury (TBI) is a result of an outside force causing immediate mechanical disruption of brain tissue and delayed pathogenic events. In order to examine injury processes associated with TBI, a number of rodent models to induce brain trauma have been described. However, none of these models covers the entire spectrum of events that might occur in TBI. Here we provide a thorough methodological description of a straightforward closed head weight drop mouse model to assess brain injuries close to the clinical conditions of human TBI. PMID- 22300473 TI - Characterization of diabetic microaneurysms by simultaneous fluorescein angiography and spectral-domain optical coherence tomography. AB - PURPOSE: To correlate spectral-domain optical coherence tomography (SD-OCT) findings of perfused diabetic microaneurysms with leakage status on fluorescein angiography (FA) using simultaneous FA and SD-OCT. DESIGN: Retrospective, observational case series. METHODS: A total of 173 microaneurysms were analyzed in 50 eyes (14 mild nonproliferative diabetic retinopathy [NPDR]; 22 moderate NPDR; 9 severe NPDR; 5 proliferative diabetic retinopathy) of 40 diabetic patients using simultaneous FA and SD-OCT. The characteristics of microaneurysms were evaluated by 2 masked observers using SD-OCT and correlated with leakage status on FA. RESULTS: External diameter of microaneurysms averaged 104 MUm (range 43-266 MUm). Some microaneurysm centers (15/173; 9%) and the outermost extent of microaneurysms (113/173; 68%) were localized to the outer half of the retina. Almost all microaneurysms spanned more than 1 retinal layer (157/173; 91%). Most microaneurysms had an internal lumen with homogeneous reflectivity (109/173; 63%) and moderate reflectivity (87/173; 50%). Retinal thickness through microaneurysms as well as the presence of adjacent hyporeflectivity on SD-OCT correlated with increasing leakage status seen on FA (P < .001). Microaneurysm dimensions, percent depth within the retina, retinal layer location, and internal reflectivity by SD-OCT did not correlate significantly with FA leakage status. CONCLUSIONS: Simultaneous FA and SD-OCT allows detailed characterization of perfused diabetic microaneurysms. Increased FA leakage of diabetic microaneurysms positively correlated with perianeurysm fluid and retinal thickness. Perfused microaneurysms seen by SD-OCT were localized deeper than the inner nuclear layer. PMID- 22300474 TI - Fermentation enhances the biological activity of Allium cepa bulb extracts. AB - In this study, we compared the analytical fingerprint and bioactivity of three onion extracts, including an aqueous, a methanol, and a fermented aqueous extract. The extracts were characterized by HPLC-DAD, LC-MS, and GC-MS analyses. The antibacterial, antigenotoxic, and antiproliferative activity of these extracts was assessed by means of agar disk diffusion, bacterial growth kinetics, a comet assay, cell cycle distribution analysis, and cell viability testing. Both the aqueous and methanolic extracts showed a typical flavonol-fingerprint as assessed by HPLC measurements and showed little to no bioactivity. The fermented aqueous extract, which lacks the usual onion flavonoid profile, was found to be the most active in all of the assays. This finding indicates that metabolites of onion compounds, generated by lactic acid fermentation, may be more active than their precursor substances. PMID- 22300475 TI - Effects of nanoparticle zinc oxide on spatial cognition and synaptic plasticity in mice with depressive-like behaviors. AB - BACKGROUND: Nanomaterials, as a new kind of materials, have been greatly applied in different fields due to their special properties. With the industrialization of nanostructured materials and increasing public exposure, the biosafety and potential influences on central nervous system (CNS) have received more attention. Nanosized zinc oxide (nanoZnO) was suggested to up-regulate neuronal excitability and to induce glutamate release in vitro. Therefore, we hypothesized nanoparticles of nanoZnO may lead to changes in balance of neurotransmitter or neuronal excitability of CNS. This study was to investigate if there were effects of nanoZnO on animal model of depression. METHODS: Male Swiss mice were given lipopolysaccharides (LPS, 100 MUg/kg, 100 MUg/ml, every other day, 8 times, i.p.) from weaning to induce depressive-like behaviors. NanoZnO (5.6 mg/kg, 5.6 mg/ml, every other day, 8 times, i.p.) was given as the interaction. The mouse model was characterized using the methods of open field test, tail suspension test and forced swim test. Furthermore, the spatial memory was evaluated using Morris water maze (MWM) and the synaptic plasticity was assessed by measuring the long term potentiation (LTP) in the perforant pathway (PP) to dentate gyrus (DG) in vivo. RESULTS: Results indicated that model mice showed disrupted spatial memory and LTP after LPS injections and the behavioral and electrophysiological improvements after nanoZnO treatment. CONCLUSION: Data suggested that nanoZnO may play some roles in CNS of mental disorders, which could provide some useful direction on the new drug exploring and clinical researches. PMID- 22300476 TI - High energy conversion efficiency in nanofluidic channels. AB - It is proposed that the layering of large ions at the wall/liquid interface of nanofluidic channels can be used to achieve high efficiency (possibly >50%) in the conversion of hydrostatic energy into electrical power. Large ions tend to produce peaks and troughs in their concentration profiles at charged walls, producing high concentrations far from the walls where the ions' pressure-driven velocity is high. This increases the streaming conductance and the energy conversion efficiency. PMID- 22300477 TI - "Magic goggles": a distraction technique for pediatric dermatology procedures. AB - The sight of needles and surgical equipment can often cause anxiety in children. We describe the use of "Magic Goggles," a distraction technique of use in pediatric dermatology procedures. PMID- 22300478 TI - With respect to elderly patients: finding kidneys in the context of new allocation concepts. AB - The elderly have benefited from increased access to renal transplantation in recent years. New allocation concepts would shift distribution of kidneys to younger recipients, making expanded criteria and living donor kidneys more relevant for seniors. Current issues impacting expanded criteria donor kidney availability and living donor transplant opportunities for the elderly are explored. It is hoped that the kidney donor profile index will improve risk assessment and utilization of marginal kidneys. The usefulness of procurement biopsy remains controversial. Dual kidney transplantation and machine perfusion appear to be effective mechanisms to increase organ availability. "Old-for-old" allocation systems, donation service area variation and regulatory and reimbursement issues highlight disparities and disincentives affecting expanded criteria donor organ utilization, and considerations for the way forward are discussed. Living donor transplantation, even with older donors, may provide the best option for elderly recipients, and careful expansion of the living donor pool appears appropriate. In light of new allocation concepts, it will be important to understand issues pertinent to seniors and develop effective strategies to maintain or improve their access to the benefits of transplantation. PMID- 22300479 TI - Outbreaks of virulent diarrheagenic Escherichia coli--are we in control? AB - Shiga toxin-producing Escherichia coli (STEC) are the most virulent diarrheagenic E. coli known to date. They can be spread with alarming ease via food as exemplified by a large sprout-borne outbreak of STEC O104:H4 in 2011 that was centered in northern Germany and affected several countries. Effective control of such outbreaks is an important public health task and necessitates early outbreak detection, fast identification of the outbreak vehicle and immediate removal of the suspected food from the market, flanked by consumer advice and measures to prevent secondary spread.In our view, opportunities to improve control of STEC outbreaks lie in early clinical suspicion for STEC infection, timely diagnosis of all STEC at the serotype-level and integrating molecular subtyping information into surveillance systems. Furthermore, conducting analytical studies that supplement patients' imperfect food history recall and performing, as an investigative element, product tracebacks, are pivotal but underutilized tools for successful epidemiologic identification of the suspected vehicle in foodborne outbreaks. As a corollary, these tools are amenable to tailor microbiological testing of suspected food. Please see related article: http://www.biomedcentral.com/1741-7015/10/12. PMID- 22300480 TI - How does muscle stiffness affect the internal deformations within the soft tissue layers of the buttocks under constant loading? AB - Mechanical loading of soft tissues covering bony prominences can cause skeletal muscle damage, ultimately resulting in a severe pressure ulcer termed deep tissue injury (DTI). Deformation plays an important role in the aetiology of DTI. Therefore, it is essential to minimise internal muscle deformations in subjects at risk of DTI. As an example, spinal cord-injured (SCI) individuals exhibit structural changes leading to a decrease in muscle thickness and stiffness, which subsequently increase the tissue deformations. In the present study, an animal specific finite element model, where the geometry and boundary conditions were derived from magnetic resonance images, was developed. It was used to investigate the internal deformations in the muscle, fat and skin layers of the porcine buttocks during loading. The model indicated the presence of large deformations in both the muscle and the fat layers, with maximum shear strains up to 0.65 in muscle tissue and 0.63 in fat. Furthermore, a sensitivity analysis showed that the tissue deformations depend considerably on the relative stiffness values of the different tissues. For example, a change in muscle stiffness had a large effect on the muscle deformations. A 50% decrease in stiffness caused an increase in maximum shear strain from 0.65 to 0.99, whereas a 50% increase in stiffness resulted in a decrease in maximum shear strain from 0.65 to 0.49. These results indicate the importance of restoring tissue properties after SCI, with the use of, for example, electrical stimulation, to prevent the development of DTI. PMID- 22300481 TI - Fukushima fallout at Milano, Italy. AB - The radionuclides (131)I, (137)Cs and (134)Cs were observed in the Milano region (45 degrees ) of Italy early after the nuclear accident in Fukushima, Japan. Increased atmospheric radioactivity was observed on an air filter taken on 30 March 2011, while the maximum activity of 467 MUBq m(-3) for (131)I was recorded at April 3-4, 2011. The first evidence of Fukushima fallout was confirmed with (131)I and (137)Cs measured in precipitation at two sampling sites at Milano on 28 March, 2011, with the concentrations of (131)I and (137)Cs in the rainwater equal to 0.89 Bq L(-1) and 0.12 Bq L(-1), respectively. A sample of dry deposition that was collected 9 days after the first rainfall event of 27-28 March, 2011 showed that the dry deposition was more effective in the case of (137)Cs than it was for (131)I, probably because iodine was mainly in gaseous form whereas caesium was rapidly bound to aerosols and thus highly subject to dry deposition. The relatively high observed values of (137)Cs in grass, soil and fresh goat and cow milk samples were probably from Chernobyl fallout and global fallout from past nuclear tests rather than from the Fukushima accident. Finally, a dose assessment for the region of investigation showed clearly that the detected activities in all environmental samples were very far below levels of concern. PMID- 22300482 TI - Airborne fission products in the High Arctic after the Fukushima nuclear accident. AB - High-volume aerosol samples were collected at the Mt. Zeppelin Global Atmosphere Watch station, Ny-Alesund, Svalbard (78 degrees 58'N, 11 degrees 53'E). The samples were analysed to find out if the radionuclide emissions from the Fukushima nuclear power plant accident in March 2011 could be detected also in the atmosphere of the High Arctic. Iodine-131 and (134)Cs and (137)Cs were observed from 25 March 2011 onwards. The maximum (131)I, (134)Cs and (137)Cs activity concentrations were 810 +/- 20, 659 +/- 13, and 675 +/- 7 MUBq/m(3), respectively. The comparison between the measured (131)I activity concentrations at Mt. Zeppelin and those calculated with the SILAM dispersion model revealed that the timing of plume movements could be rather well predicted with the model. The activity concentration levels between the measurements and the model calculations deviated. This can be due to the inaccuracies in the source term. The (134)Cs:(137)Cs activity ratio recorded in Svalbard was high compared to earlier incidents. The ratio was close to 1 which is in agreement with other studies of the Fukushima releases. This distinctive activity ratio in the Fukushima debris could be used as a tracer in Arctic radioecology studies if the activity concentrations are high enough to be detected. PMID- 22300483 TI - Nanotitanium dioxide toxicity in mouse lung is reduced in sanding dust from paint. AB - BACKGROUND: Little is known of how the toxicity of nanoparticles is affected by the incorporation in complex matrices. We compared the toxic effects of the titanium dioxide nanoparticle UV-Titan L181 (NanoTiO2), pure or embedded in a paint matrix. We also compared the effects of the same paint with and without NanoTiO2. METHODS: Mice received a single intratracheal instillation of 18, 54 and 162 MUg of NanoTiO2 or 54, 162 and 486 MUg of the sanding dust from paint with and without NanoTiO2. DNA damage in broncheoalveolar lavage cells and liver, lung inflammation and liver histology were evaluated 1, 3 and 28 days after intratracheal instillation. Printex 90 was included as positive control. RESULTS: There was no additive effect of adding NanoTiO2 to paints: Therefore the toxicity of NanoTiO2 was reduced by inclusion into a paint matrix. NanoTiO2 induced inflammation in mice with severity similar to Printex 90. The inflammatory response of NanoTiO2 and Printex 90 correlated with the instilled surface area. None of the materials, except of Printex 90, induced DNA damage in lung lining fluid cells. The highest dose of NanoTiO2 caused DNA damage in hepatic tissue 1 day after intratracheal instillation. Exposure of mice to the dust from paints with and without TiO2 was not associated with hepatic histopathological changes. Exposure to NanoTiO2 or to Printex 90 caused slight histopathological changes in the liver in some of the mice at different time points. CONCLUSIONS: Pulmonary inflammation and DNA damage and hepatic histopathology were not changed in mice instilled with sanding dust from NanoTiO2 paint compared to paint without NanoTiO2. However, pure NanoTiO2 caused greater inflammation than NanoTiO2 embedded in the paint matrix. PMID- 22300484 TI - Outcomes of trauma patients: direct transport versus transfer after stabilisation at another hospital. AB - BACKGROUND: In this study, we attempted to identify differences in the outcomes of patients with severe trauma who were directly transported to our hospital, and those who were stabilised initially at other hospitals in south-central Taiwan. METHODS: We performed a prospective observational study to review the records of 231 patients with major trauma (Injury Severity Scores (ISS) >15) who visited our hospital's emergency department from January 2010 to December 2010. Among these patients, 75 were referred from other hospitals. Logistic regression was performed to assess the effects of transfer on mortality. RESULTS: Patients in the transfer group had a shorter interval between trauma and admission to the first hospital (25.3 min vs. 28.1 min), and the average interval between the two hospital arrivals was 138.3 min. Transfer from another hospital was not significantly correlated with mortality in this study (odds ratio: 1.124, 95% confidence interval: 0.276-4.578). CONCLUSION: In trauma patients with ISS>15, there is no difference in mortality between those transferred from another hospital after initial stabilisation and those who visited our emergency department directly. PMID- 22300485 TI - Biodiversity as a barrier to glioma cell invasion. AB - Gliomas are extremely aggressive and lethal forms of brain cancer. Unlike many other cancer types, glioma cells rarely metastasize. They spread throughout the brain and invasiveness of glioma cells is a major cause of therapeutic failure. In plant ecosystem, biodiversity acts locally as a barrier to ecological invasion. By analogy, we hypothesize that the low cell diversity of differentiated tissues, a counterpart of their functional specificity, opens the way to local cancer cell invasion. Seeding the brain tumor microenvironment with heterogeneous cell populations could be a mean to limit cancer cell invasion by enhancing cell biodiversity. PMID- 22300486 TI - The validity of amnestic MCI and non-amnestic MCI at age 75 in the prediction of Alzheimer's dementia and vascular dementia. AB - BACKGROUND: Clinical subtypes of mild cognitive impairment (MCI) were assigned as potential prodromes to various types of dementia. Amnestic MCI (aMCI) is said to have a high likelihood of progressing to Alzheimer's dementia (AD) and non amnestic MCI (naMCI) subtypes are assumed to have a higher likelihood of progressing to non-AD dementia. The aim of this study was to investigate the prognostic accuracy of aMCI and naMCI for the development of AD, vascular dementia (VaD), and mixed dementia. METHODS: In this longitudinal study, 487 subjects without dementia (cognitively healthy: n = 387; MCI cases: n = 115) aged 75 years at baseline, who participated in a population-based cohort study (Vienna Transdanube Aging study), were available for analysis. The observation period was 90 months. The diagnoses of the clinical MCI subtypes were made according to common criteria. The outcome (AD, VaD, mixed dementia) was described for both MCI subtypes. Diagnostic values of aMCI and naMCI according to incident AD, VaD, and mixed dementia were determined. RESULTS: AD was the most common type of dementia following both MCI subtypes. Participants with aMCI were more likely to progress to AD than participants with naMCI. The proportion of incident VaD and mixed dementia did not differ concerning the MCI subtypes. The positive predictive value for both MCI subtypes was low (range: 1%-46%), whereas the negative predictive value was high (range: 86%-99%). CONCLUSIONS: The increased risk of clinical MCI subtypes for a particular type of dementia could only be confirmed for aMCI and incident AD. PMID- 22300487 TI - Intravenous labetalol compared with intravenous nicardipine in the management of hypertension in critically ill patients. AB - BACKGROUND: Critically ill patients with acute hypertension often require titratable rapid blood pressure (BP) reductions using parenteral administration of drugs. There are few comparative studies available to make informed drug product selection decisions. The purpose of this study was to evaluate the short term clinical outcomes and costs of intravenous labetalol or intravenous nicardipine in the management of hypertension in critically ill patients. METHODS: This study was a retrospective analysis of consecutive patients receiving intravenous labetalol or intravenous nicardipine in the intensive care unit with acute elevations in either systolic (>160 mm Hg) or diastolic (>90 mm Hg) BP. Patient demographics, clinical characteristics, and short-term clinical outcomes were abstracted from the medical record. Hospital costs were calculated from hospital billing forms. RESULTS: A total of 189 patients receiving labetalol and 193 patients receiving nicardipine were included in the analysis. The average hourly dose was 37.3 +/- 9.4 mg/h for labetalol compared with 7.1 +/- 5.6 mg/h for nicardipine (P < .001). The average total dose of labetalol was 170.9 +/- 32.6 mg compared with 112.2 +/- 29.1 mg for nicardipine (P = .02). The duration of therapy was significantly shorter for labetalol (8.2 +/- 6.2 hours) compared with nicardipine (15.8 +/- 4.4 hours) (P = .03). There were a greater number of dose titrations with labetalol (6.1 +/- 6.2) than with nicardipine (4.7 +/- 4.9), but this difference was not significantly different (P = .29). There were no significant differences in the magnitude of the average change in systolic (P = .79) or diastolic (P = .82) BP between labetalol and nicardipine. The proportion of patients achieving their BP targets was significantly greater with nicardipine (83%) than with labetalol (67%) (P = .04). The proportion of patients requiring an alternate antihypertensive agent was significantly greater with labetalol than with nicardipine (31% vs 17%; P = .02). The total number of all-cause adverse events was significantly greater with labetalol (61%) than with nicardipine (48%) (P = .04). Labetalol was associated with a significantly greater incidence of hypotension and bradycardia or atrioventricular block compared with nicardipine. There was no significant difference in the frequency of other adverse events between these 2 drugs. The median hospital costs were not significantly different between patients receiving labetalol and patients receiving nicardipine. CONCLUSION: Our study suggests that nicardipine is a more effective antihypertensive agent than labetalol in an unselected group of patients who develop hypertension in the intensive care unit setting. A major advantage of nicardipine compared with labetalol was fewer adverse effects. Nicardipine was associated with less hypotension and bradycardia or atrioventricular block, resulting in a lower rate of drug discontinuation compared with labetalol. PMID- 22300488 TI - Use of wireless motility capsule to determine gastric emptying and small intestinal transit times in critically ill trauma patients. AB - PURPOSE: The purpose of this study is to use a novel wireless motility capsule to compare gastric emptying and small bowel transit times in critically ill trauma patients and healthy volunteers. MATERIALS AND METHODS: We evaluated gastric emptying, small bowel transit time, and total intestinal transit time in 8 critically ill trauma patients. These data were compared with those obtained in 87 healthy volunteers from a separate trial. Data were obtained with a motility capsule that wirelessly transmitted pH, pressure, and temperature to a recorder attached to each subject's abdomen. RESULTS: The gastric emptying time was significantly longer in critically ill patients (median, 13.9; interquartile range [IQR], 6.6-48.3 hours) than in healthy volunteers (median, 3.0; IQR, 2.5 3.9 hours), P < .001. The small bowel transit time in critically ill patients was significantly longer than in healthy volunteers (median, 6.7 hours; IQR, 4.4-8.5 hours vs median, 3.8 hours; IQR, 3.1-4.7 hours), P = .01. Furthermore, the capsules passed after 10 (IQR, 8.5-13) days in the critical care group and 1.2 (IQR, 0.9-1.9) days in healthy volunteers (P < .001). CONCLUSIONS: Both gastric emptying and small bowel transit were delayed in critically ill trauma patients. PMID- 22300489 TI - Variation in the care of septic shock: the impact of patient and hospital characteristics. AB - PURPOSE: The aim of this study was to examine treatments of septic shock in a sample of US hospitals and to assess whether patient and hospital characteristics are associated with use of sepsis therapies. MATERIALS AND METHODS: We studied 192 hospitals that treated 50 or more adults with septic shock between 2004 and 2006. We examined hospital-level variation in commonly used therapies including mechanical ventilation, activated protein C (APC), hydrocortisone, central venous pressure (CVP) monitoring, albumin/colloid, and pulmonary artery catheters. We calculated interquartile range to assess the hospital-level variation in treatment. We developed hierarchical mixed-effects logistic regression models to examine the association between patient and hospital characteristics and selected treatments. RESULTS: A total of 22702 patients met the inclusion criteria. When compared with patients younger than 45 years, patients 75 years or older were as likely to receive mechanical ventilation but less likely to receive APC (odds ratio [OR], 0.35 [95% confidence interval, 0.27-0.45]), hydrocortisone (OR, 0.65 [0.56-0.75]), or CVP monitoring (OR, 0.73 [0.63-0.84]). Compared with whites, black patients were more likely to be mechanically ventilated (OR, 1.15 [1.05 1.25]) but less likely to receive hydrocortisone (OR, 0.86 [0.78-0.95]) or APC (0.70 [0.58-0.86]). CONCLUSION: Treatment of septic shock varies across hospitals. In contrast to mechanical ventilation, treatments with weaker supporting evidence showed greater variation, especially among black and older patients. PMID- 22300490 TI - The role of total bile acid in oral secretions in ventilator-associated pneumonia. AB - PURPOSE: The aim of this study was to investigate the role of inflammatory biomarkers and total bile acid (TBA) in oral secretions in the development of ventilator-associated pneumonia (VAP). MATERIALS: This prospective study was conducted in an intensive care unit. Oral secretions were collected from mechanically ventilated patients who met the selection criteria for VAP prevention protocol. The levels of interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor alpha, soluble intercellular adhesion molecule-1, monocyte chemoattractant protein-1, C-reactive protein, surfactant protein D, and TBA in oral secretions were measured and compared between the patients with and those without VAP. RESULTS: Thirty-nine patients with and 39 patients without VAP were studied. The levels of inflammatory biomarkers in oral secretions showed no significant difference between the 2 groups. However, the patients with VAP had significantly higher values of TBA in oral secretions than did those without VAP (median and 25th-75th interquartile range, 9.59 and 1.37-24.66 MUmol/L vs 2.74 and 0.00-8.22 MUmol/L; P < .003). No significant correlations were found between TBA and inflammatory biomarkers in oral secretions. CONCLUSIONS: Duodenogastroesophageal reflux as evidenced by the presence of TBA in oral secretions is common in mechanically ventilated patients and may play a role in the development of VAP. PMID- 22300491 TI - Comparative study of pressure- and volume-controlled ventilation on stroke volume variation as a predictor of fluid responsiveness in patients undergoing major abdominal surgery. AB - PURPOSE: We hypothesized that the 2 ventilation modes might have a different influence on the stroke volume variation (SVV). This study investigated the effect of the ventilation modes on SVV as a predictor of fluid responsiveness during major abdominal surgery. MATERIALS AND METHODS: Sixty patients were randomly allocated to volume-controlled ventilation (VCV, n = 30) or pressure controlled ventilation (PCV, n = 30) modes. After the induction of anesthesia, hemodynamic variables and SVV were measured before and after volume expansion (VE) with colloid solution of 10 mL/kg. The ability of SVV to predict the fluid responsiveness was tested by calculation of the area under a receiver operating characteristic curve for an increase in stroke volume index of at least 15% after VE. RESULTS: There were 10 and 16 responders in the VCV and PCV groups, respectively. The area under a receiver operating characteristic curve (95% confidence interval) for SVV before VE was 0.723 (0.538-0.907) and 0.799 (0.625 0.973) in the VCV and PCV groups, respectively. The optimal threshold value of SVV was 11% and 14% in the VCV and PCV groups, respectively. CONCLUSIONS: Stroke volume variation can predict fluid responsiveness during both VCV and PCV modes. However, the optimal threshold values of SVV may differ according to the ventilation modes. PMID- 22300492 TI - Association of platelet counts decline and mortality in severely burnt patients. AB - Although the dramatic fluctuation of platelet counts (PCs) has always been observed in severely burnt patients, the underlying relationship between the decline of PCs and mortality has never been well defined. In this study, we evaluated the prognostic implications of PC decline in severely burnt patients. We performed a 3-year retrospective chart of adult patients with a burn index of 50 or greater admitted to 2 burn centers. A total of 97 survivors and 51 nonsurvivors were included in this study. The trends of PCs in 2 groups within first 10 days after admission are seen to constitute 2 stages, with a slump to a nadir during the first 3 days and then a variable recovery. With respect to 30 day mortality, the areas under the receiver operating characteristic curve for the percentage decline of PCs (PPC) during the first 3 days and Acute Physiology And Chronic Health Evaluation II score were 0.784 and 0.871, respectively (P = .0549). Furthermore, an optimal cutoff of PPC during the first 3 days, which discriminated survivors with nonsurvivors, was 65.53% using the maximum Youden index (0.4853). Although the sensitivity and specificity of PPC during the first 3 days were not as high as the Acute Physiology And Chronic Health Evaluation II score in the present study, Kaplan-Meier estimation and multiple logistic regression models both indicated that a PPC of 65% or greater during the first 3 days was significantly associated with 30-day death (odds ratio, 1.054; 95% confidence interval, 1.006-1.104; P = .028). In summary, an initial slump of PCs, especially a PPC of 65% or greater during the first 3 days, provides prognostic significance for 30-day mortality in severely burnt patients. PMID- 22300493 TI - Clotrimazole and enilconazole distribution within the frontal sinuses and nasal cavity of nine dogs with sinonasal aspergillosis. AB - OBJECTIVES: Multiple topical treatments are often required for clinical cure of mycotic rhinosinusitis in dogs. The objective of this study was to describe the distribution and retention of enilconazole and clotrimazole solutions using a temporary trephination protocol. METHODS: Nine client-owned dogs diagnosed with mycotic rhinosinusitis between March 2008 and December 2009 were prospectively enrolled and were sequentially allocated to receive treatment with either clotrimazole (1% in polyethylene glycol) or enilconazole (10% solution), after imaging and rhinoscopic assessment. Both frontal sinuses were trephined, debrided and flushed with saline. Infusion was administered via frontal sinuses with dogs in sternal recumbency and computed tomography (CT) performed 5 minutes after completion. Distribution was scored 1 to 4 at the canine tooth, premolar 4, cribriform plate and frontal sinus on both sides, for a maximum score of 32. RESULTS: Distribution of antifungal agents to all regions of the nasal cavity and frontal sinuses was achievable, but varied considerably. Retention was poor in 10 of 18 regions assessed. CLINICAL SIGNIFICANCE: Distribution of antifungal agents within the frontal sinuses is achievable using temporary trephination; however, distribution is variable and retention is often poor. PMID- 22300495 TI - Phenotypic and genetic divergence among harbour porpoise populations associated with habitat regions in the North Sea and adjacent seas. AB - Determining the mechanisms that generate population structure is essential to the understanding of speciation and the evolution of biodiversity. Here, we investigate a geographical range that transects two habitat gradients, the North Sea to North Atlantic transition, and the temperate to subpolar regions. We studied the harbour porpoise (Phocoena phocoena), a small odontocete inhabiting both subpolar and temperate waters. To assess differentiation among putative populations, we measured morphological variation at cranial traits (N = 462 individuals) and variation at eight microsatellite loci for 338 of the same individuals from Norwegian, British and Danish waters. Significant morphological differentiation reflected the size of the buccal cavity. Porpoises forage in relatively shallow waters preying mainly on benthic species in British and Danish waters, and on mesopelagic and pelagic fish off the coast of Norway. We suggest that the observed differentiation may be explained by resource specialization and either adaptation or developmental responses to different local habitats. PMID- 22300494 TI - Banff 2011 Meeting report: new concepts in antibody-mediated rejection. AB - The 11th Banff meeting was held in Paris, France, from June 5 to 10, 2011, with a focus on refining diagnostic criteria for antibody-mediated rejection (ABMR). The major outcome was the acknowledgment of C4d-negative ABMR in kidney transplants. Diagnostic criteria for ABMR have also been revisited in other types of transplants. It was recognized that ABMR is associated with heterogeneous phenotypes even within the same type of transplant. This highlights the necessity of further refining the respective diagnostic criteria, and is of particular significance for the design of randomized clinical trials. A reliable phenotyping will allow for definition of robust end-points. To address this unmet need and to allow for an evidence-based refinement of the Banff classification, Banff Working Groups presented multicenter data regarding the reproducibility of features relevant to the diagnosis of ABMR. However, the consensus was that more data are necessary and further Banff Working Group activities were initiated. A new Banff working group was created to define diagnostic criteria for ABMR in kidneys independent of C4d. Results are expected to be presented at the 12th Banff meeting to be held in 2013 in Brazil. No change to the Banff classification occurred in 2011. PMID- 22300496 TI - Biodynamers: self-organization-driven formation of doubly dynamic proteoids. AB - Polypeptide-type dynamic biopolymers (biodynamers) have been generated by polycondensation via acylhydrazone and imine formation of amino-acid-derived components that polymerize driven by self-organization. They have been characterized as globular particles, reminiscent of folded proteins, by cryo-TEM, LS, DOSY NMR, and SANS studies. The reversible polymers obtained show remarkably low dispersity and feature double covalent dynamics allowing for fine-tuning of both exchange and incorporation processes through pH control. In the course of build-up, they perform a selection of the most suitable building block, as indicated by the preferential incorporation of the more hydrophobic amino-acid component with increased rate and higher molecular weight of the polymer formed. The system described displays nucleation-elongation behavior driven by hydrophobic effects and represents a model for the operation of adaptation processes in the evolution of complex matter. PMID- 22300497 TI - Linking structural change with functional regulation-insights from mass spectrometry. AB - A wide range of biophysical approaches has been applied to structural biology, all with the same overall goal-to understand the molecular machines that allow cells to function. While knowledge of the identity and composition of component protein subunits is an important foundation for understanding these macromolecular complexes it has become increasingly clear that knowledge of the exact composition alone is insufficient for understanding dynamic interactions and regulatory mechanisms. In this review we focus on recent developments of mass spectrometry (MS) that allow us to unravel the functional 'secrets' of non covalent molecular machines. PMID- 22300498 TI - Three-dimensional tumour volume and cancer-specific survival for patients undergoing nephrectomy to treat pT1 clear-cell renal cell carcinoma. AB - Study Type - Prognosis (case series) Level of Evidence 4. What's known on the subject? and What does the study add? The positive association of tumour size (largest tumour dimension on pathology review) and risk of RCC progression and survival following nephrectomy is well documented. Moreover, several clinicopathological scoring systems (i.e. nomograms and algorithms) have been developed to predict outcomes for surgically treated RCC patients and each of these includes tumour size as an independent predictor of RCC outcome. There is still the question of whether information on three-dimensional tumour volume (cm(3) ) can provide additional prognostic information, particularly among patients with small pT1 tumours where the range of tumour size is more limited. Our study demonstrates that increasing tumour volume is associated with a greater risk of RCC-specific death in patients with pT1 ccRCC, with a more pronounced association in pT1a tumours specifically. In addition, we observed evidence that tumour volume may provide more accurate prognostic information than tumour size alone in pT1a patients. Tumour volume may add prognostic information specifically in pT1a RCC. OBJECTIVE: To address whether information on three-dimensional tumour volume can provide additional prognostic information for patients with small, localized renal cell carcinoma (RCC) superior to tumour size alone. PATIENTS AND METHODS: We identified 955 patients treated with radical nephrectomy or nephron-sparing surgery for unilateral, sporadic, pT1, pN0/NX, M0, non-cystic clear-cell RCC (ccRCC) between 1980 and 2004, including 515 pT1a patients and 440 pT1b patients. * We estimated tumour volume using three tumour dimensions recorded on pathological analysis and the equation for the volume of an ellipsoid [pi/6 (length * width * height)]. For tumour size alone, we used the maximum tumour diameter recorded on pathological analysis. * Univariate and multivariable associations with RCC-specific death were evaluated using Cox proportional hazards regression models summarized with hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among pT1a patients, the risk of RCC death associated with having a tumour volume above the median (HR = 4.55; 95% CI, 1.30-15.83; P= 0.018) was markedly higher than having a tumour size above the median (HR = 2.55; 95% CI 0.83-7.85; P= 0.10). Comparison of concordance (c) index values further supported the idea that additional prognostic information was provided by tumour volume (c= 0.659) compared with tumour size (c= 0.600) for pT1a patients. * Among pT1b patients, we noted that associations of tumour volume and tumour size with RCC-specific death were similar. * Multivariable adjustment did not alter our findings. CONCLUSIONS: Tumour volume could provide valuable prognostic information for patients with pT1a ccRCC but not pT1b ccRCC. * Future investigations are needed to confirm this finding, explore other RCC subtypes and evaluate accuracy of tumour volume determination on radiographic imaging for potential patient management before surgery. PMID- 22300499 TI - A distinct metabolic signature predicts development of fasting plasma glucose. AB - BACKGROUND: High blood glucose and diabetes are amongst the conditions causing the greatest losses in years of healthy life worldwide. Therefore, numerous studies aim to identify reliable risk markers for development of impaired glucose metabolism and type 2 diabetes. However, the molecular basis of impaired glucose metabolism is so far insufficiently understood. The development of so called 'omics' approaches in the recent years promises to identify molecular markers and to further understand the molecular basis of impaired glucose metabolism and type 2 diabetes. Although univariate statistical approaches are often applied, we demonstrate here that the application of multivariate statistical approaches is highly recommended to fully capture the complexity of data gained using high throughput methods. METHODS: We took blood plasma samples from 172 subjects who participated in the prospective Metabolic Syndrome Berlin Potsdam follow-up study (MESY-BEPO Follow-up). We analysed these samples using Gas Chromatography coupled with Mass Spectrometry (GC-MS), and measured 286 metabolites. Furthermore, fasting glucose levels were measured using standard methods at baseline, and after an average of six years. We did correlation analysis and built linear regression models as well as Random Forest regression models to identify metabolites that predict the development of fasting glucose in our cohort. RESULTS: We found a metabolic pattern consisting of nine metabolites that predicted fasting glucose development with an accuracy of 0.47 in tenfold cross validation using Random Forest regression. We also showed that adding established risk markers did not improve the model accuracy. However, external validation is eventually desirable. Although not all metabolites belonging to the final pattern are identified yet, the pattern directs attention to amino acid metabolism, energy metabolism and redox homeostasis. CONCLUSIONS: We demonstrate that metabolites identified using a high-throughput method (GC-MS) perform well in predicting the development of fasting plasma glucose over several years. Notably, not single, but a complex pattern of metabolites propels the prediction and therefore reflects the complexity of the underlying molecular mechanisms. This result could only be captured by application of multivariate statistical approaches. Therefore, we highly recommend the usage of statistical methods that seize the complexity of the information given by high-throughput methods. PMID- 22300500 TI - Regional variations in canine descending aortic tissue mechanical properties change with formalin fixation. AB - BACKGROUND/INTRODUCTION: Diseases of the aorta can alter the local mechanical properties of the tissue, leading to aneurysms and plaque instability. Local tissue properties are best evaluated from surgical samples or autopsy tissue using mechanical testing ex vivo. We examined whether formalin-fixed tissues preserve regional and local variations in tissue properties when compared to fresh tissues in order to determine if fixed tissue can be used to infer mechanical changes associated with tissue remodeling. METHODS: Equibiaxial mechanical tests were performed on canine descending thoracic aorta to quantify the regional and local tissue stiffness. Samples were taken from four locations along the aorta and from the lateral and medial side at each location. Half of the samples were randomly formalin fixed and used to measure the effect of fixation on local thickness, stiffness, and anisotropy. RESULTS: In fresh tissue, regional differences in tissue stiffness and thickness are present. Aortic tissue stiffens and thins along the aorta. Fixation did not alter thickness, significantly increased tissue stiffness, and altered the directional dependency of the mechanical properties (anisotropy) at low strain. Formalin fixation altered local stiffness of the aorta near the aortic arch. CONCLUSION: The changes in mechanical properties along the aorta were preserved in formalin-fixed samples. However, our results show that formalin fixation can change the variation in tissue stiffness and significantly affects the anisotropic properties of vascular tissues. Formalin fixation introduces spurious changes in mechanical properties, and we therefore strongly recommend the use of fresh aortic tissues for biomechanical analysis. PMID- 22300501 TI - Primary and metastatic cardiac tumors: imaging characteristics, surgical treatment, and histopathological spectrum: a 10-year-experience at a German heart center. AB - BACKGROUND: Tumors of the heart are rare compared to other cardiac diseases. Their clinical symptoms vary from absent to nonspecific. This great variation and general paucity of symptoms related to cardiac tumors often result in delayed diagnosis and treatment. METHODS: We retrospectively evaluated all patients who underwent cardiac surgery for a space-occupying lesion in the observation period between 2000 and 2010 at our hospital. Clinicopathological features, imaging characteristics, and disease outcomes were analyzed, and the results were compared with the available English literature. RESULTS: During the last 10 years, 84 patients underwent resection of a cardiac mass at our center, i.e., 0.85% of the total number (n=9829) of all cardiac surgical operations performed in that period. The part of primary cardiac tumors was 73.8% (n=62; 59 benign and 3 malign tumors). In nine cases (10.7%), secondary cardiac tumors represented metastases of malignant tumors from different extracardiac locations. In 13 cases (15.5%), the mass represented cardiac thrombus. The majority of cardiac tumors were benign, and most of them were cardiac myxomas (n=48). Papillary fibroelastoma was the second most common primary tumor. CONCLUSIONS: Our data in this study were comparable to the literature regarding the frequency and allocation of the different cardiac tumors. Our data are in line with previous reports that patients with benign cardiac tumors profit from surgical resection compared to those subjected to conservative treatment with the risk of central or peripheral embolisms. Concerning malignant primary cardiac tumors and cardiac metastases, surgery represents only a palliative strategy in most of the cases. PMID- 22300502 TI - Deletion of tenascin-C gene exacerbates atherosclerosis and induces intraplaque hemorrhage in Apo-E-deficient mice. AB - AIMS: Tenascin-C (TNC), a matricellular protein, is up-regulated in atherosclerotic plaques. We investigated whether the deletion of TNC gene affects the development of atherosclerosis in a murine model. METHODS: TNC-/-/apo E-/- mice were generated and used for atherosclerosis studies. We compared these results to those observed in control groups of apo E-/- mice. RESULTS: The en face analysis of aortic area showed that the mean aortic lesion area of the double knockout (KO) mice was significantly higher than that of control mice at different times after feeding of atherogenic diet; the accumulation of lesional macrophages and lipids was significantly higher. Analysis of cell adhesion molecules revealed that vascular cell adhesion molecule-1 (VCAM-1), but not intercellular adhesion molecule-1, was up-regulated 1 week after feeding of atherogenic diet in the double KO mouse as compared to apo E-/- mouse. Cell culture studies revealed that the expression of VCAM-1 in endothelial cells isolated from the double KO mouse is more sensitive to the tumor necrosis factor alpha stimulation than the cells isolated from apo E-/- mice. Cell adhesion studies showed that the adherence of RAW monocytic cells to the endothelial cells was significantly enhanced in the cultured endothelial cells from the TNC gene deleted cells. Following the prolonged feeding of an atherogenic diet (28-30 weeks), the aortic and carotid atherosclerotic lesions frequently demonstrated large grossly visible areas of intraplaque hemorrhage in the double KO mice compared to control. CONCLUSIONS: These data unveil a protective role for TNC in atherosclerosis and suggest that TNC signaling may have the potential to reduce atherosclerosis, in part by modulating VCAM-1 expression. PMID- 22300503 TI - Retrospective analysis of stored dried blood spots from children with cystic fibrosis and matched controls to assess the performance of a proposed newborn screening protocol in Switzerland. AB - BACKGROUND: Newborn screening (NBS) for Cystic Fibrosis (CF) has been introduced in many countries, but there is no ideal protocol suitable for all countries. This retrospective study was conducted to evaluate whether the planned two step CF NBS with immunoreactive trypsinogen (IRT) and 7 CFTR mutations would have detected all clinically diagnosed children with CF in Switzerland. METHODS: IRT was measured using AutoDELFIA Neonatal IRT-Kit in stored NBS cards. RESULTS: Between 2006 and 2009, 66 children with CF were reported, 4 of which were excluded for various reasons (born in another country, NBS at 6 months, no informed consent). 98% (61/62) had significantly higher IRT compared to matched control group. There was one false negative IRT result in an asymptomatic child with atypical CF (normal pancreatic function and sweat test). CONCLUSIONS: All children but one with atypical CF would have been detected with the planned two step protocol. PMID- 22300505 TI - From hospital to home: a brief nurse practitioner intervention for vulnerable older adults. AB - A randomized controlled trial was conducted to evaluate the impact of a brief nurse practitioner (NP) intervention on care transitions among older hospitalized adults discharged to home (N = 199). Immediately following discharge, participants randomly assigned to the intervention received up to three home visits and two telephone calls from a registered NP that included medication review, care coordination, assessment of medical care needs, and brief coaching in self-management skills. Usual care participants received all standard medical care, including access to case management services. Intervention participants reported improved satisfaction with medical care (p = 0.008) and self-efficacy in managing medical conditions (p = 0.001) and had fewer primary care visits (p = 0.036) but no change in hospital readmissions at 6 months following enrollment. These findings suggest that intervening at the point of transition may extend the reach of the primary care physician by improving patient outcomes through nursing support at a high-risk period of care-the transition from hospital to home. PMID- 22300504 TI - Ozone-induced lung injury and sterile inflammation. Role of toll-like receptor 4. AB - Inhalation of toxic doses of ozone is associated with a sterile inflammatory response characterized by an accumulation of macrophages in the lower lung which are activated to release cytotoxic/proinflammatory mediators that contribute to tissue injury. Toll-like receptor 4 (TLR4) is a pattern recognition receptor present on macrophages that has been implicated in sterile inflammatory responses. In the present studies we used TLR4 mutant C3H/HeJ mice to analyze the role of TLR4 in ozone-induced lung injury, oxidative stress and inflammation. Acute exposure of control C3H/HeOuJ mice to ozone (0.8ppm for 3h) resulted in increases in bronchoalveolar lavage (BAL) lipocalin 24p3 and 4-hydroxynonenal modified protein, markers of oxidative stress and lipid peroxidation. This was correlated with increases in BAL protein, as well as numbers of alveolar macrophages. Levels of surfactant protein-D, a pulmonary collectin known to regulate macrophage inflammatory responses, also increased in BAL following ozone inhalation. Ozone inhalation was associated with classical macrophage activation, as measured by increased NF-kappaB binding activity and expression of TNFalpha mRNA. The observation that these responses to ozone were not evident in TLR4 mutant C3H/HeJ mice demonstrates that functional TLR4 contributes to ozone induced sterile inflammation and macrophage activation. PMID- 22300506 TI - Is low dose inhaled corticosteroid therapy as effective for inflammation and remodeling in asthma? A randomized, parallel group study. AB - BACKGROUND: While most of the clinical benefits of inhaled corticosteroid (ICS) therapy may occur at low doses, results of dose-ranging studies are inconsistent. Although symptom/lung function response to low and high dose ICS medication is comparable, it is uncertain whether low dose ICSs are as effective as high dose in the treatment of inflammation and remodeling. METHODS: 22 mild or moderate asthmatic adult subjects (corticosteroid free for > 2 months) participated in a randomized, parallel group study to compare effects of fluticasone propionate (FP) 200 mcg/day and 1000 mcg/day. Alveolar macrophage (AM)-derived cytokines and basement membrane thickness (BMT) were measured at baseline and after 7 weeks treatment while symptoms, spirometry, exhaled nitric oxide (eNO) and airway hyperresponsiveness (AHR) to mannitol at baseline and 6 weeks. RESULTS: FP improved spirometry, eNO, symptoms and AHR with no difference between low and high dose FP. Both high and low dose FP reduced GM-CSF, TNF-alpha and IL-1ra, with no change in BMT and with no differences between low and high dose FP. CONCLUSIONS: 200 MUg/day of FP was as effective as 1000 MUg/day in improving asthma control, airway inflammation, lung function and AHR in adults in the short term. Future studies should examine potential differential effects between low and high dose combination therapy (ICS/long acting beta agonist) on inflammation and airway remodeling over longer treatment periods. PMID- 22300507 TI - How O-substitution of sialyl donors affects their stereoselectivity. AB - The profound effect of substituents at C-5 of glycosyl sialosides on their stereoselectivity is well-known although the exact nature of this effect is somewhat less understood. Presented herein is a comparative study of a range of novel sialyl donors with various O-substituents. It is demonstrated that O substituents at C-4 and C-7 may also have a significant effect on the reactivity of sialyl donors and on the stereoselectivity of chemical sialylation. PMID- 22300508 TI - Differential expression of microRNAs during allograft rejection. AB - MicrorRNA are small noncoding RNA molecules that regulate the posttranscriptional expression of target genes. In addition to being involved in many biologic processes, microRNAs are important regulators in innate and adaptive immune responses. Distinct sets of expressed microRNAs are found in different cell types and tissues and aberrant expression of microRNAs is associated with many disease states. MicroRNA expression was examined in a model of heterotopic heart transplantation by microarray analyses and a unique profile was detected in rejecting allogeneic transplants (BALB/c -> C57BL/6) as compared to syngeneic transplants (C57BL/6 -> C57BL/6). The microRNA miR-182 was significantly increased in rejecting cardiac allografts and in mononuclear cells that infiltrate the grafts. Forkhead box (FOX) proteins are a family of important transcription factors and FOXO1 is a target of miR-182. As miR-182 increases after transplant, there is a concomitant posttranscriptional decrease in FOXO1 expression in heart allografts that is localized to both the cardiomyocytes and CD3(+) T cells. The microRNA miR-182 is significantly increased in both peripheral blood mononuclear cells and plasma during graft rejection suggesting potential as a biomarker of graft status. Our results identify microRNAs that may regulate alloimmune responses and graft outcomes. PMID- 22300509 TI - Organic complexed superphosphates (CSP): physicochemical characterization and agronomical properties. AB - A new type of superphosphate (organic complexed superphosphate (CSP)) has been developed by the introduction of organic chelating agents, preferably a humic acid (HA), into the chemical reaction of single superphosphate (SSP) production. This modification yielded a product containing monocalcium phosphate complexed by the chelating organic agent through Ca bridges. Theoretically, the presence of these monocalcium-phosphate-humic complexes (MPHC) inhibits phosphate fixation in soil, thus increasing P fertilizer efficiency. This study investigateed the structural and functional features of CSP fertilizers produced employing diverse HA with different structural features. To this end were used complementary analytical techniques: solid-phase 31P NMR, 13C NMR, laser-confocal microscopy, X ray diffraction, and molecular modeling. Finally, the agronomical efficiency of four CSP have been compared with that of SSP as P sources for wheat plants grown in both alkaline and acidic soils in greenhouse pot trials under controlled conditions. The results obtained from the diverse analytical studies showed the formation of MPHC in CSP. Plant-soil studies showed that CSP products were more efficient than SSP in providing available phosphate for wheat plants cultivated in various soils with different physicochemical features. This fact is probably associated with the ability of CSP complexes to inhibit phosphate fixation in soil. PMID- 22300511 TI - Constructed molecular sensor to enhance metal detection by bacterial ribosomal switch-ion channel protein interaction. AB - Molecular biosensors are useful tools that detect metal ions or other potentially toxic chemicals. However, the efficiency of conventional sensors is limited in mixed metals substrates, which is the common way they are found in nature. The use of biosensors constructed from genetically modified living microbial systems has the potential of providing sensitive detection systems for specific toxic targets. Consequently, our investigation was aimed at assembling different genetic building blocks to produce a focused microbial biosensor with the ability to detect specific metals. This objective was achieved by using a synthetic biology approach. Our genetic building blocks, including a synchronized ribosomal switch-iron ion channel, along with sequences of promoters, metal-binding proteins (Fe, Pb), ribosomal binding sites, yellow fluorescence reporter protein (YFRP), and terminators, were constructed within the same biobrick in Escherichia coli. We used an rpoS ribosomal switch containing an aptamer, which responds to the specific metal ligands, in synchronization with an iron ion channel, TonB. This switch significantly stimulates translation, as expressed by higher fluorescence, number of colonies, and concentration of RNA in E. coli. The positive results show the effectiveness of using genetically tailored synchronized ribosomal switch-ion channels to construct microbial biosensors to detect specific metals, as tested in iron solutions. PMID- 22300510 TI - Treatment of enterohemorrhagic Escherichia coli (EHEC) infection and hemolytic uremic syndrome (HUS). AB - Verotoxigenic Escherichia coli (VTEC) are a specialized group of E. coli that can cause severe colonic disease and renal failure. Their pathogenicity derives from virulence factors that enable the bacteria to colonize the colon and deliver extremely powerful toxins known as verotoxins (VT) or Shiga toxins (Stx) to the systemic circulation. The recent devastating E. coli O104:H4 epidemic in Europe has shown how helpless medical professionals are in terms of offering effective therapies. By examining the sources and distribution of these bacteria, and how they cause disease, we will be in a better position to prevent and treat the inevitable future cases of sporadic disease and victims of common source outbreaks. Due to the complexity of pathogenesis, it is likely a multitargeted approach is warranted. Developments in terms of these treatments are discussed. PMID- 22300512 TI - Oriented immobilization of the tobacco etch virus protease for the cleavage of fusion proteins. AB - The tobacco etch virus (TEV) protease is a useful tool for the removal of fusion tags from recombinant proteins. The difficulty in obtaining this enzyme led us to look for an optimal method for its use. In this work, we produced both the wild type and the S219V mutant TEV proteases fused to the Streptag II affinity sequence (Streptag II-TEV(WT), and Streptag II-TEV(S219V), respectively). The two enzymes were affinity immobilized on a streptavidin-agarose matrix and compared to their respective free forms. Both immobilized Streptag II-TEV(WT) and Streptag II-TEV(S219V) were active on the 74-kDa Streptag II substrate with a retained activity of 83.5% and 81%, respectively compared to their free corresponding forms. The slight enzyme activity decrease caused by the immobilization was balanced by the enhanced stability and the successful repetitive use of the proteolytic columns. Thus, the wild-type and the mutant immobilized proteases were used, during a period of 18 months, for nine batch reactions with retention of 38% and 51% of their initial activities, respectively. The present results demonstrate that immobilized TEV protease on streptavidin-agarose is an attractive and efficient tool for fusion protein cleavage, especially when the target protein is fused to a streptagged fusion partner. Using this strategy, the total process can be shortened by performing the cleavage and the recovery of the purified target protein in one step. PMID- 22300513 TI - Laboratory-developed test--SynFRAME: an approach for assessing laboratory developed tests synthesized from prior appraisal frameworks. AB - Since the late 1990 s, there has been an unprecedented growth in the development of new molecular and proteomic assays for clinical decision making. Despite the thousands of tests available, a standardized, well-defined, and coherent evaluation framework for these molecular assays is still lacking. We aim to summarize the publicly available appraisal criteria and to develop a succinct and accessible set of criteria that can provide a roadmap for the appraisal of gene based laboratory developed tests (LDTs). We conducted a systematic literature review of the available molecular diagnostic framework in PubMed MD and CINAHL and identified 91 articles on existing appraisal criteria. We provided a summary of the historical appraisal system and developed an analysis of these appraisal systems, LDT-SynFRAME, which details the major criteria for evaluating molecular diagnostics in the clinical setting. Our goal with the LDT-SynFRAME system is to promote a well-informed dialog among all the stakeholders responsible for the development, approval, reimbursement, and use of new molecular classifiers. PMID- 22300514 TI - Carbon black nanoparticle instillation induces sustained inflammation and genotoxicity in mouse lung and liver. AB - BACKGROUND: Widespread occupational exposure to carbon black nanoparticles (CBNPs) raises concerns over their safety. CBNPs are genotoxic in vitro but less is known about their genotoxicity in various organs in vivo. METHODS: We investigated inflammatory and acute phase responses, DNA strand breaks (SB) and oxidatively damaged DNA in C57BL/6 mice 1, 3 and 28 days after a single instillation of 0.018, 0.054 or 0.162 mg Printex 90 CBNPs, alongside sham controls. Bronchoalveolar lavage (BAL) fluid was analyzed for cellular composition. SB in BAL cells, whole lung and liver were assessed using the alkaline comet assay. Formamidopyrimidine DNA glycosylase (FPG) sensitive sites were assessed as an indicator of oxidatively damaged DNA. Pulmonary and hepatic acute phase response was evaluated by Saa3 mRNA real-time quantitative PCR. RESULTS: Inflammation was strongest 1 and 3 days post-exposure, and remained elevated for the two highest doses (i.e., 0.054 and 0.162 mg) 28 days post exposure (P < 0.001). SB were detected in lung at all doses on post-exposure day 1 (P < 0.001) and remained elevated at the two highest doses until day 28 (P < 0.05). BAL cell DNA SB were elevated relative to controls at least at the highest dose on all post-exposure days (P < 0.05). The level of FPG sensitive sites in lung was increased throughout with significant increases occurring on post exposure days 1 and 3, in comparison to controls (P < 0.001-0.05). SB in liver were detected on post-exposure days 1 (P < 0.001) and 28 (P < 0.001). Polymorphonuclear (PMN) cell counts in BAL correlated strongly with FPG sensitive sites in lung (r = 0.88, P < 0.001), whereas no such correlation was observed with SB (r = 0.52, P = 0.08). CBNP increased the expression of Saa3 mRNA in lung tissue on day 1 (all doses), 3 (all doses) and 28 (0.054 and 0.162 mg), but not in liver. CONCLUSIONS: Deposition of CBNPs in lung induces inflammatory and genotoxic effects in mouse lung that persist considerably after the initial exposure. Our results demonstrate that CBNPs may cause genotoxicity both in the primary exposed tissue, lung and BAL cells, and in a secondary tissue, the liver. PMID- 22300515 TI - When the profession becomes personal: dementia care practitioners as family caregivers. AB - BACKGROUND: Little is known about the impact of caring experience on the practice of dementia care professionals. Few research studies covering dementia practice ask about personal experiences of providing care or having a family member with dementia. In England and Wales, the Mental Capacity Act (MCA) 2005 provided a new legal framework for planning and decision-making in the event of possible loss of capacity. Professional activities in this area include advice and assistance with arranging proxy decision-making, establishing wishes, and advance decisions. The aim of this paper is to present interview data from dementia care professionals with family experiences of dementia and their reflections on decision-making frameworks. METHODS: A total of 123 dementia care professionals working in community and care home settings were interviewed (2007-2010) about their experiences and expectations of the MCA 2005. Additional questions covered experiences of being family members or carers of a person with dementia and any use of the planning and decision-making provisions of the MCA in personal and family contexts. Data were analyzed thematically. RESULTS: Seventy practitioners had experience of family members with dementia and family caring. Decision-making and planning were viewed as easier under the MCA but tensions could arise around loss of decision-making capacity or family dispute. Empathy for caregiving situations and how things could have been different were reflected upon. CONCLUSIONS: Trainers, clinical supervisors, and researchers in dementia care may build upon personal experience of some practitioners to promote empathy with other family carers and the provision of timely information and advice. PMID- 22300516 TI - The New Phytologist Tansley Medal 2011. PMID- 22300517 TI - A molecular guide to the taxonomy of arbuscular mycorrhizal fungi. PMID- 22300518 TI - Safe sex in plants. PMID- 22300519 TI - Hsp70 protein levels and thermotolerance in Drosophila subobscura: a reassessment of the thermal co-adaptation hypothesis. AB - Theory predicts that geographic variation in traits and genes associated with climatic adaptation may be initially driven by the correlated evolution of thermal preference and thermal sensitivity. This assumes that an organism's preferred body temperature corresponds with the thermal optimum in which performance is maximized; hence, shifts in thermal preferences affect the subsequent evolution of thermal-related traits. Drosophila subobscura evolved worldwide latitudinal clines in several traits including chromosome inversion frequencies, with some polymorphic inversions being apparently associated with thermal preference and thermal tolerance. Here we show that flies carrying the warm-climate chromosome arrangement O(3+4) have higher basal protein levels of Hsp70 than their cold-climate O(st) counterparts, but this difference disappears after heat hardening. O(3+4) carriers are also more heat tolerant, although it is difficult to conclude from our results that this is causally linked to their higher basal levels of Hsp70. The observed patterns are consistent with the thermal co-adaptation hypothesis and suggest that the interplay between behaviour and physiology underlies latitudinal and seasonal shifts in inversion frequencies. PMID- 22300520 TI - A common peripheral blood gene set for diagnosis of operational tolerance in pediatric and adult liver transplantation. AB - To identify biomarkers of operational tolerance in pediatric and adult liver transplant recipients, transcriptional profiles were examined from 300 samples by microarrays and Q-PCR measurements of blood specimens from pediatric and adult liver transplant recipients and normal tissues. Tolerance-specific genes were validated in independent samples across two different transplant programs and validated by Q-PCR. A minimal set of 13 unique genes, highly expressed in natural killer cells (p = 0.03), were significantly expressed in both pediatric and adult liver tolerance, irrespective of different clinical and demographic confounders. The performance of this gene set by microarray in independent samples was 100% sensitivity and 83% specificity and the AUC was 0.988 for only three genes by Q PCR. 26% of adults and 64% of children with excellent liver allograft function, on minimal or dual immunosuppression, showed high prediction scores for tolerance. Novel peripheral transcriptional profiles can be identified in operational tolerance in pediatric and adult recipients of liver allografts, suggesting a high incidence of a pro-tolerogenic phenotype in stable patients on chronic immunosuppression. Given the high incidence of viral infections and malignancies in liver transplant recipients, this gene set provides an important monitoring tool that can move the field toward personalized and predictive medicine in organ transplantation. PMID- 22300521 TI - Rectangular bunched rutile TiO2 nanorod arrays grown on carbon fiber for dye sensitized solar cells. AB - Because of their special application in photovoltaics, the growth of one dimensional single-crystalline TiO(2) nanostructures on a flexible substrate is receiving intensive attention. Here we present a study of rectangular bunched TiO(2) nanorod (NR) arrays grown on carbon fibers (CFs) from titanium by a "dissolve and grow" method. After a corrosion process in a strong acid solution, every single nanorod is etched into a number of small nanowires. Tube-shaped dye sensitized solar cells are fabricated by using etched TiO(2) NRs-coated CFs as the photoanode. An absolute energy conversion efficiency of 1.28% has been demonstrated under 100 mW cm(-2) AM 1.5 illumination. This work demonstrates an innovative method for growing bunched TiO(2) NRs on flexible substrates that can be applied in flexible devices for energy harvesting and storage. PMID- 22300522 TI - Analysis of the salivary microbiome using culture-independent techniques. AB - BACKGROUND: The salivary microbiota is a potential diagnostic indicator of several diseases. Culture-independent techniques are required to study the salivary microbial community since many of its members have not been cultivated. METHODS: We explored the bacterial community composition in the saliva sample using metagenomic whole genome shotgun (WGS) sequencing, the extraction of 16S rRNA gene fragments from metagenomic sequences (16S-WGS) and high-throughput sequencing of PCR-amplified bacterial 16S rDNA gene (16S-HTS) regions V1 and V3. RESULTS: The hierarchical clustering of data based on the relative abundance of bacterial genera revealed that distances between 16S-HTS datasets for V1 and V3 regions were greater than those obtained for the same V region with different numbers of PCR cycles. Datasets generated by 16S-HTS and 16S-WGS were even more distant. Finally, comparison of WGS and 16S-based datasets revealed the highest dissimilarity.The analysis of the 16S-HTS, WGS and 16S-WGS datasets revealed 206, 56 and 39 bacterial genera, respectively, 124 of which have not been previously identified in salivary microbiomes. A large fraction of DNA extracted from saliva corresponded to human DNA. Based on sequence similarity search against completely sequenced genomes, bacterial and viral sequences represented 0.73% and 0.0036% of the salivary metagenome, respectively. Several sequence reads were identified as parts of the human herpesvirus 7. CONCLUSIONS: Analysis of the salivary metagenome may have implications in diagnostics e.g. in detection of microorganisms and viruses without designing specific tests for each pathogen. PMID- 22300523 TI - Identifying changes in comfort and worry among pediatric nursing students following clinical rotations. AB - Pediatric nursing clinicals often cause feelings of worry, thus hindering students' discovery. This study sought to identify worry-provoking elements before and after pediatric clinical rotations. Participants included 100 pediatric nursing students. A descriptive, exploratory, quantitative design was used to explore student worry using the Pediatric Student Comfort and Worry Assessment Tool. Pre- and post-test scores were calculated to evaluate changes in worry and comfort. The item that changed the most was comfort in assessment, whereas worry regarding causing a child pain changed the least. These data suggest the significant need in identifying worries to improve confidence in performance for pediatric clinical. PMID- 22300524 TI - Administration burden associated with recombinant human growth hormone treatment: perspectives of patients and caregivers. AB - Patients treated with recombinant human growth hormone (rhGH) for growth hormone disorders follow a challenging treatment schedule. This study assessed patient and caregiver experiences with rhGH therapy treatment regimens. Patients 13 years or older with growth hormone deficiency and caregivers completed Web-based surveys. A total of 61 patients and 239 caregivers participated. Storage of rhGH was considered burdensome by more than a third. More than 51% considered storage "somewhat more" to "much more of a burden" relative to the burden while not traveling. "Away from home or traveling" was the most frequently endorsed reason for missing a dose. rhGH treatment while traveling is challenging because of rhGH storage burden. PMID- 22300525 TI - Rb1 mRNA expression in developing mouse teeth. AB - Rb1 is a tumor suppressor gene that regulates cell cycle progression through interactions with E2F transcription factors. In recent years, new roles for Rb1 in regulating cellular differentiation have also emerged. For example, it has been shown that Rb1 regulates osteoblast differentiation in a cell cycle independent manner, by binding to the transcription factor Runx2, and facilitating the up-regulation of late bone differentiation markers. Based on the facts that Runx2 also functions in tooth development, and that little is known about potential roles for Rb1 in mammalian tooth development, here we evaluated the expression of Rb1 mRNA in developmentally staged mouse teeth. Our data show that Rb1 mRNA is expressed in both dental epithelial and dental mesenchymal progenitor cells. In addition, Rb1 mRNA appears upregulated in differentiating ameloblasts and odontoblasts, suggesting roles for Rb1 in tooth differentiation. PMID- 22300526 TI - Mechanisms of alloimmunization and subsequent bone marrow transplantation rejection induced by platelet transfusion in a murine model. AB - For many nonmalignant hematological disorders, HLA-matched bone marrow transplantation (BMT) is curative. However, due to lack of neoplasia, the toxicity of stringent conditioning regimens is difficult to justify, and reduced intensity conditioning is used. Unfortunately, current reduced intensity regimens have high rates of BMT rejection. We have recently reported in a murine model that mHAs on transfused platelet products induce subsequent BMT rejection. Most nonmalignant hematological disorders require transfusion support prior to BMT and the rate of BMT rejection in humans correlates with the number of transfusions given. Herein, we perform a mechanistic analysis of platelet transfusion-induced BMT rejection and report that unlike exposure to alloantigens during transplantation, platelet transfusion primes alloimmunity but does not stimulate full effector function. Subsequent BMT is itself an additional and distinct immunizing event, which does not induce rejection without antecedent priming from transfusion. Both CD4(+) and CD8(+) T cells are required for priming during platelet transfusion, but only CD8(+) T cells are required for BMT rejection. In neither case are antibodies required for rejection to occur. PMID- 22300527 TI - The identification and interpretation of differences in the transcriptomes of organically and conventionally grown potato tubers. AB - In the European integrated research project SAFEFOODS, one of the aims was to further establish the potential of transcriptomics for the assessment of differences between plant varieties grown under different environmental conditions. Making use of the knowledge of cellular processes and interactions is one of the ways to obtain a better understanding of the differences found with transcriptomics. For the present study the potato genotype Sante was grown under both organic and conventional fertilizer, and each combined with either organic or conventional crop protection, giving four different treatments. Samples were derived from the European project QualityLowInputFood (QLIF). Microarray data were analyzed using different statistical tools (multivariate, principal components analysis (PCA); univariate, analysis of variance (ANOVA)) and with pathway analysis (hypergeometric distribution (HGD) and gene set enrichment analysis (GSEA)). Several biological processes were implicated as a result of the different treatments of the plants. Most obvious were the lipoxygenase pathway, with higher expression in organic fertilizer and lower expression in organic crop protection; the starch synthase pathway, with higher expression in both organic crop protection and fertilizer; and the biotic stress pathway, with higher expression in organic fertilizer. This study confirmed that gene expression profiling in combination with pathway analysis can identify and characterize differences between plants grown under different environmental conditions. PMID- 22300528 TI - Systemic inflammatory profile and response to anti-tumor necrosis factor therapy in chronic obstructive pulmonary disease. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by progressive worsening of airflow limitation associated with abnormally inflamed airways in older smokers. Despite correlative evidence for a role for tumor necrosis factor-alpha in the pathogenesis of COPD, the anti-tumor necrosis factor alpha, infliximab did not show clinical efficacy in a double-blind, placebo controlled, phase II clinical trial. This study sought to evaluate the systemic inflammatory profile associated with COPD and to assess the impact of tumor necrosis factor neutralization on systemic inflammation. METHODS: Serum samples (n = 234) from the phase II trial were collected at baseline and after 24 weeks of placebo or infliximab. Additionally, baseline serum samples were obtained from an independent COPD cohort (n = 160) and 2 healthy control cohorts (n = 50; n = 109). Serum concentrations of a broad panel of inflammation-associated analytes were measured using a 92-analyte multiplex assay. RESULTS: Twenty-five proteins were significantly elevated and 2 were decreased in COPD, including highly elevated CD40 ligand, brain-derived neurotrophic factor, epidermal growth factor, acute-phase proteins, and neutrophil-associated proteins. This profile was largely independent of smoking status, age, and clinical phenotype. The majority of these associations of serum analytes with COPD are novel findings. Increased serum creatine kinase-muscle/brain and myoglobin correlated modestly with decreased forced expiratory volume at 1 second, suggesting cardiac involvement. Infliximab did not affect this systemic inflammatory profile. CONCLUSIONS: A robust systemic inflammatory profile was associated with COPD. This profile was generally independent of disease severity. Because anti-tumor necrosis factor alpha did not influence systemic inflammation, how to control the underlying pathology beyond symptom suppression remains unclear. PMID- 22300529 TI - Neighborhood characteristics and depressive mood among older adults: an integrative review. AB - BACKGROUND: There is growing evidence that neighborhood environments are related to depressive mood in the general population. Older adults may be even more vulnerable to neighborhood factors than other adults. The aim of this paper is to review empirical findings on the relationships between neighborhood characteristics and depressive mood among older adults. METHODS: A search of the literature was undertaken in PsycINFO and MEDLINE. RESULTS: Nineteen studies were identified. Study designs were most often cross-sectional, included large sample sizes, and controlled for major individual characteristics. Mediational effects were not investigated. Statistical analysis strategies often included multilevel models. Spatial delimitations of neighborhood of residence were usually based on administrative and statistical spatial boundaries. Six neighborhood characteristics were assessed most often: neighborhood socioeconomic disadvantage, neighborhood poverty, affluence, racial/ethnic composition, residential stability, and elderly concentration. Selected neighborhood characteristics were associated with depressive mood after adjusting for individual variables. These associations were generally theoretically meaningful. CONCLUSIONS: Neighborhood variables seem to make a unique and significant contribution to the understanding of depressive mood among older adults. However, few studies investigated these associations and replication of results is needed. Several substantive neighborhood variables have been ignored or neglected in the literature. The implications of neighborhood effects for knowledge advancement and public health interventions remain unclear. Recommendations for future research are discussed. PMID- 22300530 TI - Synergistic cytogenetic and antineoplastic effects by the combined action of esteric steroidal derivatives of nitrogen mustards. AB - We studied the effect of five newly synthesized steroidal derivatives of nitrogen mustards. These derivatives have as alkylators either P-N, N-bis(2 chloroethyl)aminophenyl-butyrate (CHL) or P-N, N-bis(2-chloroethyl)aminophenyl acetate (PHE) groups esterified with different modified steroidal nuclei. We examined them alone or in combination, on sister chromatid exchange rates and on human lymphocyte proliferation kinetics. The antitumor activity of these compounds, alone or in combination, was also tested on Leukemia P388-bearing mice. A pronounced cytogenetic and antineoplastic action was demonstrated by the compounds that contain either PHE or CHL as alkylators and are esterified with a steroidal nucleus having added a cholestene group in the 17 position of the D ring. The exocyclical insertion of an -NHCO- group in the D-ring of the steroidal nucleus esterified with PHE (amide ester of PHE) yielded a compound demonstrating a distinct cytogenetic and antineoplastic effect. In contrast, the ketone group in the D-ring being inserted endocyclically in the steroidal nucleus (androstene) esterified with either CHL or with PHE gave negative cytogenetic and antineoplastic effects. However, the combined action of cholestene esterified with either CHL or with PHE in combination with either the androstene ester of PHE or with the androstene ester of CHL, respectively, gave synergistic cytogenetic and antineoplastic effects. Also the amide ester of PHE in combination with the androstene ester of CHL gave distinct cytogenetic and antineoplastic effects in a synergistic manner. PMID- 22300531 TI - Differences in gene expression and cytokine production by crystalline vs. amorphous silica in human lung epithelial cells. AB - BACKGROUND: Exposure to respirable crystalline silica particles, as opposed to amorphous silica, is associated with lung inflammation, pulmonary fibrosis (silicosis), and potentially with lung cancer. We used Affymetrix/GeneSifter microarray analysis to determine whether gene expression profiles differed in a human bronchial epithelial cell line (BEAS 2B) exposed to cristobalite vs. amorphous silica particles at non-toxic and equal surface areas (75 and 150 * 106MUm2/cm2). Bio-Plex analysis was also used to determine profiles of secreted cytokines and chemokines in response to both particles. Finally, primary human bronchial epithelial cells (NHBE) were used to comparatively assess silica particle-induced alterations in gene expression. RESULTS: Microarray analysis at 24 hours in BEAS 2B revealed 333 and 631 significant alterations in gene expression induced by cristobalite at low (75) and high (150 * 106MUm2/cm2) amounts, respectively (p < 0.05/cut off >= 2.0-fold change). Exposure to amorphous silica micro-particles at high amounts (150 * 106MUm2/cm2) induced 108 significant gene changes. Bio-Plex analysis of 27 human cytokines and chemokines revealed 9 secreted mediators (p < 0.05) induced by crystalline silica, but none were induced by amorphous silica. QRT-PCR revealed that cristobalite selectively up-regulated stress-related genes and cytokines (FOS, ATF3, IL6 and IL8) early and over time (2, 4, 8, and 24 h). Patterns of gene expression in NHBE cells were similar overall to BEAS 2B cells. At 75 * 106MUm2/cm2, there were 339 significant alterations in gene expression induced by cristobalite and 42 by amorphous silica. Comparison of genes in response to cristobalite (75 * 106MUm2/cm2) revealed 60 common, significant gene alterations in NHBE and BEAS 2B cells. CONCLUSIONS: Cristobalite silica, as compared to synthetic amorphous silica particles at equal surface area concentrations, had comparable effects on the viability of human bronchial epithelial cells. However, effects on gene expression, as well as secretion of cytokines and chemokines, drastically differed, as the crystalline silica induced more intense responses. Our studies indicate that toxicological testing of particulates by surveying viability and/or metabolic activity is insufficient to predict their pathogenicity. Moreover, they show that acute responses of the lung epithelium, including up-regulation of genes linked to inflammation, oxidative stress, and proliferation, as well as secretion of inflammatory and proliferative mediators, can be indicative of pathologic potential using either immortalized lines (BEAS 2B) or primary cells (NHBE). Assessment of the degree and magnitude of these responses in vitro are suggested as predictive in determining the pathogenicity of potentially harmful particulates. PMID- 22300532 TI - Combined use of delta13C, delta18O and delta15N tracks nitrogen metabolism and genotypic adaptation of durum wheat to salinity and water deficit. AB - * Accurate phenotyping remains a bottleneck in breeding for salinity and drought resistance. Here the combined use of stable isotope compositions of carbon (delta13C), oxygen (delta18O) and nitrogen (delta15N) in dry matter is aimed at assessing genotypic responses of durum wheat under different combinations of these stresses. * Two tolerant and two susceptible genotypes to salinity were grown under five combinations of salinity and irrigation regimes. Plant biomass, delta13C, delta18O and delta15N, gas-exchange parameters, ion and N concentrations, and nitrate reductase (NR) and glutamine synthetase (GS) activities were measured. * Stresses significantly affected all traits studied. However, only delta13C, delta18O, delta15N, GS and NR activities, and N concentration allowed for clear differentiation between tolerant and susceptible genotypes. Further, a conceptual model explaining differences in biomass based on such traits was developed for each growing condition. * Differences in acclimation responses among durum wheat genotypes under different stress treatments were associated with delta13C. However, except for the most severe stress, delta13C did not have a direct (negative) relationship to biomass, being mediated through factors affecting delta18O or N metabolism. Based upon these results, the key role of N metabolism in durum wheat adaptation to salinity and water stress is highlighted. PMID- 22300533 TI - Bifunctionality of the thiamin diphosphate cofactor: assignment of tautomeric/ionization states of the 4'-aminopyrimidine ring when various intermediates occupy the active sites during the catalysis of yeast pyruvate decarboxylase. AB - Thiamin diphosphate (ThDP) dependent enzymes perform crucial C-C bond forming and breaking reactions in sugar and amino acid metabolism and in biosynthetic pathways via a sequence of ThDP-bound covalent intermediates. A member of this superfamily, yeast pyruvate decarboxylase (YPDC) carries out the nonoxidative decarboxylation of pyruvate and is mechanistically a simpler ThDP enzyme. YPDC variants created by substitution at the active center (D28A, E51X, and E477Q) and on the substrate activation pathway (E91D and C221E) display varying activity, suggesting that they stabilize different covalent intermediates. To test the role of both rings of ThDP in YPDC catalysis (the 4'-aminopyrimidine as acid-base, and thiazolium as electrophilic covalent catalyst), we applied a combination of steady state and time-resolved circular dichroism experiments (assessing the state of ionization and tautomerization of enzyme-bound ThDP-related intermediates), and chemical quench of enzymatic reaction mixtures followed by NMR characterization of the ThDP-bound intermediates released from YPDC (assessing occupancy of active centers by these intermediates and rate-limiting steps). Results suggest the following: (1) Pyruvate and analogs induce active site asymmetry in YPDC and variants. (2) The rare 1',4'-iminopyrimidine ThDP tautomer participates in formation of ThDP-bound intermediates. (3) Propionylphosphinate also binds at the regulatory site and its binding is reflected by catalytic events at the active site 20 A away. (4) YPDC stabilizes an electrostatic model for the 4'-aminopyrimidinium ionization state, an important contribution of the protein to catalysis. The combination of tools used provides time-resolved details about individual events during ThDP catalysis; the methods are transferable to other ThDP superfamily members. PMID- 22300534 TI - Deleterious effect of CTLA4-Ig on a Treg-dependent transplant model. AB - Blockade of the B7:CD28 costimulatory pathway has emerged as a promising therapy to prevent allograft rejection. However, results from the belatacept phase III clinical trial demonstrated a higher rejection rate when compared to cyclosporine, raising concern about potential deleterious effects of this agent. In this study, we investigated the consequences of B7:CD28 blockade by hCTLA4Ig on regulator T cell (Treg) generation in different major histocompatibility complex (MHC) mismatch transplant models. Administration of hCTLA4Ig significantly decreased the amount of Tregs in B6 WT animals and this effect was predominant in thymus-induced Tregs (Helios(+) ). Although hCTLA4Ig prevented rejection in a fully allogeneic mismatch model, it accelerated rejection in a MHC class-II mismatch model (MST = 26, p < 0.0001), in which long-term allograft survival is dependent on Tregs. This accelerated rejection was associated with a marked reduction in thymus-induced Tregs and led to a higher effector/regulatory T-cell ratio in secondary lymphoid organs and in the allograft. This study confirms the importance of the B7:CD28 pathway in Treg homeostasis in an in vivo transplant model and suggests that hCTLA4Ig therapy may be deleterious in circumstances where engraftment is dependent on Tregs. PMID- 22300535 TI - Molecular phylogenetics reveals a pattern of biome conservatism in New World anchovies (family Engraulidae). AB - Evolutionary transitions between marine and freshwater biomes are relatively rare events, yielding a widespread pattern of biome conservatism among aquatic organisms. We investigated biome transitions in anchovies (Engraulidae), a globally distributed clade of economically important fishes. Most anchovy species are near-shore marine fishes, but several exclusively freshwater species are known from tropical rivers of South America and were previously thought to be the product of six or more independent freshwater invasions. We generated a comprehensive molecular phylogeny for Engraulidae, including representatives from 15 of 17 currently recognized genera. Our data support previous hypotheses of higher-level relationships within Engraulidae, but show that most New World genera are not monophyletic and in need of revision. Ancestral character reconstruction reveals that New World freshwater anchovies are the product of a single marine to freshwater transition, supporting a pattern of biome conservatism. We argue that competition is the principal mechanism that regulates aquatic biome transitions on a continental scale. PMID- 22300536 TI - Specific post-translational histone modifications of neutrophil extracellular traps as immunogens and potential targets of lupus autoantibodies. AB - INTRODUCTION: Autoreactivity to histones is a pervasive feature of several human autoimmune disorders, including systemic lupus erythematosus (SLE). Specific post translational modifications (PTMs) of histones within neutrophil extracellular traps (NETs) may potentially drive the process by which tolerance to these chromatin-associated proteins is broken. We hypothesized that NETs and their unique histone PTMs might be capable of inducing autoantibodies that target histones. METHODS: We developed a novel and efficient method for the in vitro production, visualization, and broad profiling of histone-PTMs of human and murine NETs. We also immunized Balb/c mice with murine NETs and profiled their sera on autoantigen and histone peptide microarrays for evidence of autoantibody production to their immunogen. RESULTS: We confirmed specificity toward acetyl modified histone H2B as well as to other histone PTMs in sera from patients with SLE known to have autoreactivity against histones. We observed enrichment for distinctive histone marks of transcriptionally silent DNA during NETosis triggered by diverse stimuli. However, NETs derived from human and murine sources did not harbor many of the PTMs toward which autoreactivity was observed in patients with SLE or in MRL/lpr mice. Further, while murine NETs were weak autoantigens in vivo, there was only partial overlap in the immunoglobulin G (IgG) and IgM autoantibody profiles induced by vaccination of mice with NETs and those seen in patients with SLE. CONCLUSIONS: Isolated in vivo exposure to NETs is insufficient to break tolerance and may involve additional factors that have yet to be identified. PMID- 22300537 TI - Markov Chain Ontology Analysis (MCOA). AB - BACKGROUND: Biomedical ontologies have become an increasingly critical lens through which researchers analyze the genomic, clinical and bibliographic data that fuels scientific research. Of particular relevance are methods, such as enrichment analysis, that quantify the importance of ontology classes relative to a collection of domain data. Current analytical techniques, however, remain limited in their ability to handle many important types of structural complexity encountered in real biological systems including class overlaps, continuously valued data, inter-instance relationships, non-hierarchical relationships between classes, semantic distance and sparse data. RESULTS: In this paper, we describe a methodology called Markov Chain Ontology Analysis (MCOA) and illustrate its use through a MCOA-based enrichment analysis application based on a generative model of gene activation. MCOA models the classes in an ontology, the instances from an associated dataset and all directional inter-class, class-to-instance and inter instance relationships as a single finite ergodic Markov chain. The adjusted transition probability matrix for this Markov chain enables the calculation of eigenvector values that quantify the importance of each ontology class relative to other classes and the associated data set members. On both controlled Gene Ontology (GO) data sets created with Escherichia coli, Drosophila melanogaster and Homo sapiens annotations and real gene expression data extracted from the Gene Expression Omnibus (GEO), the MCOA enrichment analysis approach provides the best performance of comparable state-of-the-art methods. CONCLUSION: A methodology based on Markov chain models and network analytic metrics can help detect the relevant signal within large, highly interdependent and noisy data sets and, for applications such as enrichment analysis, has been shown to generate superior performance on both real and simulated data relative to existing state-of-the-art approaches. PMID- 22300538 TI - Donor-specific HLA antibodies in a cohort comparing everolimus with cyclosporine after kidney transplantation. AB - Donor-specific HLA antibodies (DSA) have a negative impact on kidney graft survival. Therefore, we analyzed the occurrence of DSA and antibody-mediated rejection (AMR) in patients from two prospective randomized trials in our center. At 3-4.5 months posttransplant 127 patients were randomized to continue cyclosporine or converted to everolimus therapy. The presence of DSA was prospectively assessed using Luminex assays. AMR was defined according to the Banff 2009 classification. Antibody screening was available in 126 patients with a median follow-up of 1059 days. Seven out of 65 (10.8%) patients on cyclosporine developed DSA after a median of 991 days. In comparison, 14/61 patients (23.0%) randomized to everolimus developed DSA after 551 days (log-rank: p = 0.048). Eight patients on everolimus compared to two patients on cyclosporine developed AMR (log-rank: p = 0.036). Four of 10 patients with AMR-all in the everolimus group-lost their graft. A multivariate regression model revealed everolimus, >3 mismatches and living donor as significant risk factors for DSA. Acute rejection within the first year, >3 mismatches, everolimus and living donor were independent risk factors for AMR. This single center analysis demonstrates for the first time that everolimus-based immunosuppression is associated with an increased risk for the development of DSA and AMR. PMID- 22300539 TI - Neuroprotective effects of xanthohumol, a prenylated flavonoid from hops (Humulus lupulus), in ischemic stroke of rats. AB - Xanthohumol is the principal prenylated flavonoid in hops (Humulus lupulus L.), an ingredient of beer. Xanthohumol was found to be a potent chemopreventive agent; however, no data are available concerning its neuroprotective effects. In the present study, the neuroprotective activity and mechanisms of xanthohumol in rats with middle cerebral artery occlusion (MCAO)-induced cerebral ischemia were examined. Treatment with xanthohumol (0.2 and 0.4 mg/kg; intraperitoneally) 10 min before MCAO dose-dependently attenuated focal cerebral ischemia and improved neurobehavioral deficits in cerebral ischemic rats. Xanthohumol treatment produced a marked reduction in infarct size compared to that in control rats. MCAO-induced focal cerebral ischemia was associated with increases in hypoxia inducible factor (HIF)-1alpha, tumor necrosis factor (TNF)-alpha, inducible nitric oxide synthase (iNOS), and active caspase-3 protein expressions in ischemic regions. These expressions were obviously inhibited by treatment with xanthohumol. In addition, xanthohumol (3-70 MUM) concentration-dependently inhibited platelet aggregation stimulated by collagen (1 MUg/mL) in human platelet-rich plasma. An electron spin resonance (ESR) method was used to examine the scavenging activity of xanthohumol on free radicals which had formed. Xanthohumol (1.5 and 3 MUM) markedly reduced the ESR signal intensity of hydroxyl radical (OH*) formation in the H2O2/NaOH/DMSO system. In conclusion, this study demonstrates for the first time that in addition to its originally being considered an agent preventing tumor growth, xanthohumol possesses potent neuroprotective activity. This activity is mediated, at least in part, by inhibition of inflammatory responses (i.e., HIF-1alpha, iNOS expression, and free radical formation), apoptosis (i.e., TNF-alpha, active caspase-3), and platelet activation, resulting in a reduction of infarct volume and improvement in neurobehavior in rats with cerebral ischemia. Therefore, this novel role of xanthohumol may represent high therapeutic potential for treatment or prevention of ischemia-reperfusion injury-related disorders. PMID- 22300540 TI - Is that a belt or a snake? Object attentional selection affects the early stages of visual sensory processing. AB - BACKGROUND: There is at present crescent empirical evidence deriving from different lines of ERPs research that, unlike previously observed, the earliest sensory visual response, known as C1 component or P/N80, generated within the striate cortex, might be modulated by selective attention to visual stimulus features. Up to now, evidence of this modulation has been related to space location, and simple features such as spatial frequency, luminance, and texture. Additionally, neurophysiological conditions, such as emotion, vigilance, the reflexive or voluntary nature of input attentional selection, and workload have also been related to C1 modulations, although at least the workload status has received controversial indications. No information is instead available, at present, for objects attentional selection. METHODS: In this study object- and space-based attention mechanisms were conjointly investigated by presenting complex, familiar shapes of artefacts and animals, intermixed with distracters, in different tasks requiring the selection of a relevant target-category within a relevant spatial location, while ignoring the other shape categories within this location, and, overall, all the categories at an irrelevant location. EEG was recorded from 30 scalp electrode sites in 21 right-handed participants. RESULTS AND CONCLUSIONS: ERP findings showed that visual processing was modulated by both shape- and location-relevance per se, beginning separately at the latency of the early phase of a precocious negativity (60-80 ms) at mesial scalp sites consistent with the C1 component, and a positivity at more lateral sites. The data also showed that the attentional modulation progressed conjointly at the latency of the subsequent P1 (100-120 ms) and N1 (120-180 ms), as well as later latency components. These findings support the views that (1) V1 may be precociously modulated by direct top-down influences, and participates to object, besides simple features, attentional selection; (2) object spatial and non spatial features selection might begin with an early, parallel detection of a target object in the visual field, followed by the progressive focusing of spatial attention onto the location of an actual target for its identification, somehow in line with neural mechanisms reported in the literature as "object based space selection", or with those proposed for visual search. PMID- 22300541 TI - Haptoglobin 2-2 genotype is associated with increased risk of type 2 diabetes mellitus in northern Chinese. AB - The aim of this study was to investigate the association between haptoglobin (Hp) gene polymorphism and occurrence of type 2 diabetes mellitus (T2DM) in a northern Chinese population. We studied the association of the Hp gene polymorphism with T2DM in 584 unrelated T2DM patients and 690 control subjects with normal glucose tolerance among northern Chinese. The patients were diagnosed in accordance with the guidelines of the American Diabetes Association. The clinical characteristics of the study population were recorded, and the Hp genotype was determined. The frequencies of the genotypes in the group of T2DM patients and the controls were as follows: Hp2-2, 51.7% and 44.1%; Hp2-1, 39.7% and 45.1%; and Hp1-1, 8.6% and 10.9%, respectively. There was significant difference for the genotypic and allelic distribution between the two groups (p=0.021 and p=0.007, respectively). Even after readjusting for the confounding effects of age, gender, and body mass index, a significant effect of genotypes on T2DM was still found in the recessive model for the Hp2 allele tested (p=0.002). Those who had the Hp2-2 genotype had a significantly higher risk for T2DM than those with other genotypes (odds ratio=1.441, 95% confidence interval=1.143-1.817). The results showed that the Hp2-2 genotype is associated with increased risk of T2DM in the northern Chinese Han population. PMID- 22300542 TI - Using informant reports to detect cognitive decline in mild cognitive impairment. AB - BACKGROUND: The use of informant rating scales in older adults at risk of dementia may assist with early detection and intervention strategies. This study aims to evaluate whether informants rate greater cognitive change in patients with mild cognitive impairment (MCI) compared to cognitively intact individuals, and to determine the relationship between informant ratings of cognitive change and neuropsychological performance. METHODS: One hundred and nine health-seeking older adults underwent clinical and neuropsychological assessments, and informants completed the Cambridge Behavioral Inventory-Revised (CBI-R). Patients were rated according to MCI criteria, including amnestic and non-amnestic subtypes, or as being cognitively intact. CBI-R ratings were evaluated with respect to MCI diagnosis and neuropsychological performance. RESULTS: Compared to cognitively intact individuals, informants rated patients with MCI as having significantly more change in overall functioning (p < 0.05) as well as in specific domains of memory and orientation (p < 0.01), everyday skills (p < 0.05), and motivation (p < 0.05), even after controlling for depressive symptom severity. In further analyses, the non-amnestic MCI subgroup only had more informant-rated mood changes compared to the amnestic subgroup. In relation to neuropsychological performance, informant ratings were related to poorer visual memory, verbal learning and memory, language, and psychomotor speed, with correlations ranging from -0.19 to -0.43 (p < 0.05). CONCLUSIONS: These findings indicate that informants are sensitive to subtle early cognitive change in individuals with MCI, and that their ratings are related to objectively measured neuropsychological performance. Thus, the CBI-R may be valuable in assisting early screening and intervention processes. PMID- 22300543 TI - Comment on "Randomized intervention study of solar disinfection of drinking water in the prevention of dysentery in Kenyan children aged under 5 years". PMID- 22300544 TI - Design of a bioactive small molecule that targets the myotonic dystrophy type 1 RNA via an RNA motif-ligand database and chemical similarity searching. AB - Myotonic dystrophy type 1 (DM1) is a triplet repeating disorder caused by expanded CTG repeats in the 3'-untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. The transcribed repeats fold into an RNA hairpin with multiple copies of a 5'CUG/3'GUC motif that binds the RNA splicing regulator muscleblind-like 1 protein (MBNL1). Sequestration of MBNL1 by expanded r(CUG) repeats causes splicing defects in a subset of pre-mRNAs including the insulin receptor, the muscle-specific chloride ion channel, sarco(endo)plasmic reticulum Ca(2+) ATPase 1, and cardiac troponin T. Based on these observations, the development of small-molecule ligands that target specifically expanded DM1 repeats could be of use as therapeutics. In the present study, chemical similarity searching was employed to improve the efficacy of pentamidine and Hoechst 33258 ligands that have been shown previously to target the DM1 triplet repeat. A series of in vitro inhibitors of the RNA-protein complex were identified with low micromolar IC(50)'s, which are >20-fold more potent than the query compounds. Importantly, a bis-benzimidazole identified from the Hoechst query improves DM1-associated pre-mRNA splicing defects in cell and mouse models of DM1 (when dosed with 1 mM and 100 mg/kg, respectively). Since Hoechst 33258 was identified as a DM1 binder through analysis of an RNA motif-ligand database, these studies suggest that lead ligands targeting RNA with improved biological activity can be identified by using a synergistic approach that combines analysis of known RNA-ligand interactions with chemical similarity searching. PMID- 22300545 TI - Barley mutants with low rates of endosperm starch synthesis have low grain dormancy and high susceptibility to preharvest sprouting. AB - * Studies of embryo dormancy in relation to preharvest sprouting (PHS) in cereals have focused on ABA and other hormones. The relationship between these phenomena and the rate of grain filling has not been investigated. * A collection of barley mutants impaired in starch synthesis was assessed for preharvest sprouting in the field. In subsequent glasshouse experiments, developing grains were assayed for germination index, sugars, abscisic acid (ABA) and the effects of temperature and exogenous ABA on germination. * Mutant lines displayed greater preharvest sprouting in the field than parental lines. In the glasshouse, nondeep physiological dormancy was reduced in developing grains of five lines with mutations affecting proteins involved in endosperm starch synthesis. Inhibition of germination by exogenous ABA and elevated temperature was decreased in developing mutant grains. Sugar concentrations were high but embryo and endosperm ABA contents were unaltered. * We reveal a direct connection between grain filling and the extent of grain dormancy. Impaired endosperm starch synthesis directly influences the acquisition of embryo dormancy, perhaps because endosperm sugar concentrations modulate the ABA responsiveness of the embryo. Thus environmental or genetic factors that reduce grain filling are likely to reduce dormancy and enhance susceptibility to PHS. PMID- 22300546 TI - Capillary ion electrophoresis of inorganic anions and uric acid in human saliva using a polyvinyl alcohol coated capillary column and hexamethonium chloride as additive of background electrolyte. AB - A combination of polyvinyl alcohol chemically coated capillary (PVA capillary) and background electrolyte (BGE) with ion-pair reagent (hexamethonium dichloride, HMC) was used on capillary ion electrophoresis-UV detection (CIE-UV) for analysis of Br-, I-, NO2-, NO3-, SCN- and uric acid in human saliva. The PVA capillary prepared in our laboratory minimized electro-osmotic flow (EOF) at the BGE in pH 3-10, and did not affect the UV detection at 210 nm by the PVA-layer on capillary wall. Therefore, use of the PVA capillary was suitable for sensitive UV detection for analyte anions, as well as suppression of protein adsorption. In this study, we optimized the BGE of 10 mM phosphate plus 10 mM HMC with applying a voltage of -15 kV. HMC as an additive to BGE could manipulate the electrophoretic mobility of anions, without electrostatic adsorption to the PVA capillary. The CIE-UV could separate and determine analyte anions in human saliva containing proteins by the direct injection without pretreatments such as dilution or deproteinization within 13 min. The relative standard deviations (n=10) were ranged of 0.5-1.6% in migration times, 2.2-6.8% in peak heights and 2.8-8.4% in peak areas. The limits of detection (S/N=3) were ranged of 3.42-6.87 MUM. The peak height of anions in this system was gradually decreased through the successive injections of saliva samples, but the problem was successfully solved by periodically conditioning the PVA capillary. The quantifiability of anions in human saliva samples by the CIE-UV was evaluated through the recoveries by standard addition methods and comparison of other representative analytical methods, as well as identification by ion chromatography (IC). From the anion analyses in 12 different saliva samples, the CIE-UV demonstrated that can obtain obvious differences in concentrations of SCN- between of smoker and non-smoker and those of uric acid between male and female with satisfactory results. PMID- 22300547 TI - Investigation of endogenous metabolic changes in the urine of pseudo germ-free rats using a metabolomic approach. AB - Gut microflora are recognized as an active metabolic compartment in whole body systems. Understanding their impact on host physiology is an ongoing process, although many studies demonstrate that they play significant roles in host life. To assess the impact of gut microflora on host physiology in normal or close to normal conditions of the intestine, we prepared pseudo germ-free rats by antibiotic treatment, and we investigated urinary metabolite profiles of pseudo germ-free rats using UPLC-QTOF-MS based on metabolomics. The repeatability and stability of the analysis were evaluated using QC samples and testmixes in both positive and negative ionization modes. When data sets were analyzed with OPLS DA, 25 metabolites related to the activities of gut microflora were identified. The changes of amino acid metabolism, especially aromatic or sulfur amino acids, and alternations of bioactive nutrients, such as isoflavonoid and riboflavin were observed in the pseudo germ-free rats. Among the sulfur amino acid metabolites, the metabolites reflecting oxidative stress increased in the urine of pseudo germ free animals, which imply that the activities of intestinal microorganisms can affect the host redox homeostasis. Altered isoflavonoid metabolism due to lack of gut bacteria may impact on steroid hormone metabolism in the body, especially estrogen metabolism. These results indicate that the some essential metabolic pathways are sensitive to the activities of gut microorganism and directly or indirectly affected by the state of intestinal bacteria, thus gut microflora plays an important role in whole body physiology. PMID- 22300548 TI - Acquired antithrombin type IIb deficiency after liver transplantation: a case report. AB - A 3-year-old girl with multifocal hepatoblastoma was referred to our clinic for living-donor liver transplantation, the patient's father being the donor. Pretransplant evaluation revealed that the father presented partial asymptomatic antithrombin (AT) deficiency, with no inherited AT deficiency found in the girl. The genetic testing showed an AT type IIb deficiency responsible for a defect in the heparin-binding region of AT which is less thrombogenic but more common than the other AT qualitative defects. Her mother was ABO incompatible. Despite the thrombophilia on the father's side, transplantation was successfully performed under replacement therapy with intravenous AT concentrate and low-molecular weight heparin thromboprophylaxis given to both the recipient and the donor. No thrombotic complications occurred. In the posttransplantation course, acquired partial AT deficiency was detected in the recipient, who received adjuvant chemotherapy without thrombotic complications. This case report highlights the relevance of full thrombophilic work-up before liver transplantation from a living donor, while illustrating that the procedure can be successfully performed in the case of AT deficiency on the donor's side provided that appropriate AT supplementation and thromboprophylaxis are administered to both the recipient and the donor. PMID- 22300549 TI - A true science of consciousness explains phenomenology: comment on Cohen and Dennett. PMID- 22300550 TI - Socioeconomic disparities in home health care service access and utilization: a scoping review. AB - Home health care services are expanding at a rapid pace in order to meet the needs of the growing population of older adults and those with chronic illnesses. Because of current restrictions on home health care as an insured service in some countries, individuals may be required to pay for some or all of their home care services out of pocket. These payments may potentially limit access to needed home care services for persons in the lowest socioeconomic strata. Previous research demonstrates a clear socioeconomic gradient in access to acute and primary care services, where those most in need of services are the most disadvantaged and under-serviced. There has been little attention paid thus far, however, to the way in which socioeconomic status may affect the receipt of home health care services. OBJECTIVE: To determine what is known from existing literature about socioeconomic disparities in home health care access and utilization. DESIGN: A scoping review was used to map the extent and nature of the literature in this area. DATA SOURCES: A search of the databases CINAHL, Medline, SocIndex and Sociological Abstracts as well as Dissertations International. REVIEW METHODS: A total of 206 potentially relevant articles were published between 2000 and April 2011. Two reviewers independently reviewed the articles, leaving 15 research articles to be included in the scoping review. RESULTS: The majority of articles reported secondary analyses of administrative datasets related to utilization of home health care. Several studies examined access and utilization using qualitative approaches. The distinction between professional and supportive home care services was not always clear in the articles. Individual and composite measures of socioeconomic status were reported, with the most frequently used indicator being income. Several studies used more complex composite ecological indicators of socieconomic status. There was general agreement that utilization of home health services favored persons with greater economic disadvantage. Education, rurality and race were less frequently reported. CONCLUSIONS: In contrast to well-documented socioeconomic gradient seen with primary and acute care services, we found general agreement that persons of lower socioeconomic status are favored and not disadvantaged in terms of home health care services. PMID- 22300551 TI - Complications following interventional laser surgery for oral cancer and precancerous lesions. AB - Interventional carbon dioxide laser surgery is the preferred method to treat oral precancerous lesions and early invasive squamous cell carcinomas (SCCs). Little is known, however, about the complications that patients experience after such treatment. We retrospectively reviewed the hospital records of 82 patients with new dysplastic oral lesions or early invasive oral SCCs treated by laser surgery in the maxillofacial unit at Newcastle General Hospital. The most common postoperative complications were pain for more than two weeks after operation (n=28), bleeding (n=4), difficulties with speech (n=5), paraesthesia of the lingual nerve (n=17), difficulty swallowing (n=2), obstructive swelling of the submandibular gland (n=22), and tethering of the tongue (n=10). Overall, 78% of patients had one or more complication. In the absence of randomised controlled trials, this study provides the best available evidence for complication rates following interventional surgery. In addition to aiding in the preoperative counselling of patients, the data will help to inform and advise patients particularly during the immediate postoperative period. PMID- 22300552 TI - Patient information preferences and behaviour in relation to oral biopsies. AB - Our aim was to study the impact of information on the behaviour of patients who were to have an oral biopsy specimen taken. Patients were randomly assigned either to be given the basic information about oral biopsy or a more extensive amount of information. The Krantz Health Opinion Survey was used as a measure of preferences in decisions made about oral biopsy, and we used a questionnaire to assess anxiety. A total of 260 patients were studied. The participants were satisfied with the information provided (both form and content), but significantly more of those given basic information would have liked to know more (p=0.02). We conclude that information exerts a clear effect on patients' attitude to oral biopsy. Provision of preoperative information leads to significantly less anxiety in all patients having a procedure under local anaesthesia. The results emphasise that patients need to be adequately informed about oral biopsy. PMID- 22300553 TI - Does quinone or phenol enrichment of humic substances alter the primary compound from a non-algicidal to an algicidal preparation? AB - Dissolved organic matter (DOM) has been shown to affect phytoplankton species directly. These interactions largely depend on the origin and molecular size of DOM and are different in prokaryotes and eukaryotes. In a preceding study, however, two humic substance preparations did not adversely affect coccal green algae or cyanobacterial growth even at high concentrations of dissolved organic carbon (DOC). These results contradicted previous findings, showing a clear, negative response of different phototrophs to much lower DOC concentrations. To test whether or not at least defined building blocks of humic substances (HSs) are effective algicidal structures, we enriched two humic preparations with hydroquinone and p-benzoquinone, respectively, and exposed two different green algae, Pseudokirchneriella subcapitata and Monoraphidium braunii, and two cyanobacterial species, Synechocystis sp. and Microcystis aeruginosa, to the unmodified and enriched HSs. As response variables, growth rates in terms of biomass increase, chlorophyll-a content, and photosynthetic yield were measured. The highest concentration (4.17 mM DOC) of the modified HSs clearly inhibited growth; the cyanobacterial species were much more sensitive than the green algal species. However, realistic ecological concentrations did not adversely affect growth. Aerating the exposure solution for 24 h strongly reduced the inhibitory effect of the modified HSs. The algicidal effect was obviously caused by monomers and not by polymerised high molecular weight HSs themselves. Furthermore, the maximum quantum yield (Phi PSII max) was stimulated in the green algal species by low and medium DOC concentrations, but reduced in the cyanobacterial species upon exposure to higher HS concentrations. The quinone- and phenol-enriched HSs only showed algicidal activity at high concentrations of 4.17 mM DOC and lost their effects over time, presumably by oxidation and subsequent polymerisation. This study confirms that the applied humic substances themselves are not effective algicides even if enriched in effective structures. PMID- 22300554 TI - Pharmaceutical and personal care products in groundwater, subsurface drainage, soil, and wheat grain, following a high single application of municipal biosolids to a field. AB - Dewatered municipal biosolids (DMBs) were applied to a field at a rate of ~22 Mg dw ha(-1) in October 2008. Pharmaceuticals and personal care products (PPCPs) were monitored in groundwater, tile drainage, soil, DMB aggregates incorporated into the soil post-land application, and in the grain of wheat grown on the field for a period of ~1 year following application. Over 80 PPCPs were analyzed in the source DMB. PPCPs selected for in-depth monitoring included: antibiotics (tetracyclines, fluoroquinolones), bacteriocides (triclosan, triclocarban), beta blockers (atenolol, propranolol, metaprolol), antidepressants (fluoxetine, citalopram, venlafaxine, sertraline), antifungals (miconazole), analgesics (acetaminophen, ibuprofen) and anticonvulsants (carbamazepine). PPCPs in tile were observed twice, ~3 weeks and 2 months post-application. Of all PPCPs measured in tile drainage, only carbamazepine, ibuprofen, acetaminophen, triclosan, triclocarban, venlafaxine, and citalopram were detected (5-74 ng L( 1)). PPCPs were not detected in groundwater >2 m depth below the soil surface, and concentrations above detection limits at 2 m depth were only observed once just after the first rain event post-application. In groundwater, all compounds found in tile, except carbamazepine, acetaminophen and citalopram, were detected (10-19 ng L(-1)). PPCPs were detected in DMB aggregates incorporated in soil up to 1 year post-application, with miconazole and fluoxetine having the lowest percent reductions over 1 year (~50%). For several compounds in these aggregates, concentration declines were of exponential decay form. No PPCPs were detected in the grain of wheat planted post-application on the field. No PPCPs were ever detected in water, soil or grain samples from the reference plot, where no DMB was applied. PMID- 22300555 TI - Identification of two new cytochrome P450 genes and RNA interference to evaluate their roles in detoxification of commonly used insecticides in Locusta migratoria. AB - Cytochrome P450 monooxygenases (cytochrome P450s), found in virtually all living organisms, play an important role in the metabolism of xenobiotics such as drugs, pesticides, and plant toxins. We have previously evaluated the responses of the oriental migratory locust (Locusta migratoria) to the pyrethroid insecticide deltamethrin and revealed that increased cytochrome P450 enzyme activity was due to increased transcription of multiple cytochrome P450 genes. In this study, we identified for the first time two new cytochrome P450 genes, which belong to two novel cytochrome P450 gene families. CYP409A1 belongs to CYP409 family whereas CYP408B1 belongs to CYP408 family. Our molecular analysis indicated that CYP409A1 was mainly expressed in fatbodies, midgut, gastric caecum, foregut and Malpighian tubules of the third- and fourth-instar nymphs, whereas CYP408B1 was mainly expressed in foregut, hindgut and muscle of the insects at all developmental stages examined. The expression of these two cytochrome P450 genes were differentially affected by three representative insecticides, including carbaryl (carbamate), malathion (organophosphate) and deltamethrin (pyrethroid). The exposure of the locust to carbaryl, malathion and deltamethrin resulted in reduced, moderately increased and significantly increased transcript levels, respectively, of the two cytochrome P450 genes. Our further analysis of their detoxification roles by using RNA interference followed by deltamethrin bioassay showed increased nymph mortalities by 21.1% and 16.7%, respectively, after CYP409A1 and CYP408B1 were silenced. These results strongly support our notion that these two new cytochrome P450 genes play an important role in deltamethrin detoxification in the locust. PMID- 22300556 TI - An attempt to electrically enhance phytoremediation of arsenic contaminated water. AB - Water polluted with arsenic presents a challenge for remediation. A combination of phyto- and electro-remediation was attempted in this study. Four tanks were setup in order to assess the arsenic removal ability of the two methods separately and in combination. Lemna minor was chosen for As remediation and collected from a ditch in Utrecht, The Netherlands. The tanks were filled with surface water without any pre-cleaning, therefore containing various elements including metals as Mn (2.9 mg L(-1)), Cu (0.05 mg L(-1)), Fe (1.39 mg L(-1)), and Ba (0.13 mg L(-1)). This water was then spiked with As and allocated to a feed container, guaranteeing a continuous flow of 0.12 mL s(-1) to each tank. Two experiments were performed: Exp. 1 with 3 consecutive stages with rising applied voltage and Exp. 2, with a constant voltage over a period of 6 d. Measurements of pH and temperature were taken every working day, as well as water samples from outlets of all tanks including feed container for control. From the present study, there was no evidence that As had been taken up by the plants, but a strong depletion of As was observed in the tanks where current was applied. Preliminary results clearly showed that applying voltage to the electrodes caused 90% removal of As from the spiked surface water. PMID- 22300557 TI - Effect of seepage conditions on chemical attenuation of arsenic by soils across an abandoned mine site. AB - The effect of seepage velocity on the As leaching/adsorption by soils collected from abandoned mine sites was evaluated under batch equilibrium and different seepage settings. The breakthrough curves (BTCs) of As leaching from the mine soil column initially displayed the peak export and gradually leveled off over the leaching experiment. A similar As peak was observed after a flow interruption period. Adsorption by downgradient soils was clearly nonlinear, as Freundlich N was <1. In the BTCs of the layered columns, where downgradient soils were overloaded above the mine soil, the extended lag period of As appearance and lower steady-state As concentration observed for slow seepage velocity supported the idea of kinetically limited As attenuation driven by soil adsorption. The perturbation of As concentration was insignificant when the intra-column As concentration gradient was higher. The As concentration drop and time to recovery were greater for less adsorptive soil and fast seepage velocity. Desorption of As from soils retrieved from both batch adsorption and column experiment demonstrate hysteric behavior. The results of this work demonstrated that the risk of As leaching from an abandoned mine site can be greatly attenuated by intermediate downgradient soils via chemical adsorption, which tends to be kinetically limited and energetically hysteric (i.e., non-identical energy pathway). PMID- 22300558 TI - Sequence of radiotherapy and chemotherapy in breast cancer after breast conserving surgery. AB - PURPOSE: The optimal sequence of radiotherapy and chemotherapy in breast conserving therapy is unknown. METHODS AND MATERIALS: From 1983 through 2007, a total of 641 patients with 653 instances of breast-conserving therapy (BCT), received both chemotherapy and radiotherapy and are the basis of this analysis. Patients were divided into three groups. Groups A and B comprised patients treated before 2005, Group A radiotherapy first and Group B chemotherapy first. Group C consisted of patients treated from 2005 onward, when we had a fixed sequence of radiotherapy first, followed by chemotherapy. RESULTS: Local control did not show any differences among the three groups. For distant metastasis, no difference was shown between Groups A and B. Group C, when compared with Group A, showed, on univariate and multivariate analyses, a significantly better distant metastasis-free survival. The same was noted for disease-free survival. With respect to disease-specific survival, no differences were shown on multivariate analysis among the three groups. CONCLUSION: Radiotherapy, as an integral part of the primary treatment of BCT, should be administered first, followed by adjuvant chemotherapy. PMID- 22300559 TI - Sexual function and the use of medical devices or drugs to optimize potency after prostate brachytherapy. AB - PURPOSE: Prospective evaluation of sexual outcomes after prostate brachytherapy with iodine-125 seeds as monotherapy at a tertiary cancer care center. METHODS AND MATERIALS: Subjects were 129 men with prostate cancer with I-125 seed implants (prescribed dose, 145 Gy) without supplemental hormonal or external beam radiation therapy. Sexual function, potency, and bother were prospectively assessed at baseline and at 1, 4, 8, and 12 months using validated quality-of life self-assessment surveys. Postimplant dosimetry values, including dose to 10% of the penile bulb (D10), D20, D33, D50, D75, D90, and penile volume receiving 100% of the prescribed dose (V100) were calculated. RESULTS: At baseline, 56% of patients recorded having optimal erections; at 1 year, 62% of patients with baseline erectile function maintained optimal potency, 58% of whom with medically prescribed sexual aids or drugs. Variables associated with pretreatment-to posttreatment decline in potency were time after implant (p = 0.04) and age (p = 0.01). Decline in urinary function may have been related to decline in potency. At 1 year, 69% of potent patients younger than 70 years maintained optimal potency, whereas 31% of patients older than 70 maintained optimal potency (p = 0.02). Diabetes was related to a decline in potency (p = 0.05), but neither smoking nor hypertension were. For patients with optimal potency at baseline, mean sexual bother scores had declined significantly at 1 year (p < 0.01). Sexual potency, sexual function, and sexual bother scores failed to correlate with any dosimetric variable tested. CONCLUSIONS: Erections firm enough for intercourse can be achieved at 1 year after treatment, but most men will require medical aids to optimize potency. Although younger men were better able to maintain erections firm enough for intercourse than older men, there was no correlation between potency, sexual function, or sexual bother and penile bulb dosimetry. PMID- 22300560 TI - Is primary prostate cancer treatment influenced by likelihood of extraprostatic disease? A surveillance, epidemiology and end results patterns of care study. AB - PURPOSE: To examine the patterns of primary treatment in a recent population based cohort of prostate cancer patients, stratified by the likelihood of extraprostatic cancer as predicted by disease characteristics available at diagnosis. METHODS AND MATERIALS: A total of 157,371 patients diagnosed from 2004 to 2008 with clinically localized and potentially curable (node-negative, nonmetastatic) prostate cancer, who have complete information on prostate specific antigen, Gleason score, and clinical stage, were included. Patients with clinical T1/T2 disease were grouped into categories of <25%, 25%-50%, and >50% likelihood of having extraprostatic disease using the Partin nomogram. Clinical T3/T4 patients were examined separately as the highest-risk group. Logistic regression was used to examine the association between patient group and receipt of each primary treatment, adjusting for age, race, year of diagnosis, marital status, Surveillance, Epidemiology and End Results database region, and county level education. Separate models were constructed for primary surgery, external beam radiotherapy (RT), and conservative management. RESULTS: On multivariable analysis, increasing likelihood of extraprostatic disease was significantly associated with increasing use of RT and decreased conservative management. Use of surgery also increased. Patients with >50% likelihood of extraprostatic cancer had almost twice the odds of receiving prostatectomy as those with <25% likelihood, and T3-T4 patients had 18% higher odds. Prostatectomy use increased in recent years. Patients aged 76-80 years were likely to be managed conservatively, even those with a >50% likelihood of extraprostatic cancer (34%) and clinical T3-T4 disease (24%). The proportion of patients who received prostatectomy or conservative management was approximately 50% or slightly higher in all groups. CONCLUSIONS: There may be underutilization of RT in older prostate cancer patients and those with likely extraprostatic disease. Because more than half of prostate cancer patients do not consult with a radiation oncologist, a multidisciplinary consultation may affect the treatment decision-making process. PMID- 22300561 TI - Similar survival with breast conservation therapy or mastectomy in the management of young women with early-stage breast cancer. AB - PURPOSE: To evaluate survival outcomes of young women with early-stage breast cancer treated with breast conservation therapy (BCT) or mastectomy, using a large, population-based database. METHODS AND MATERIALS: Using the Surveillance, Epidemiology, and End Results (SEER) database, information was obtained for all female patients, ages 20 to 39 years old, diagnosed with T1-2 N0-1 M0 breast cancer between 1990 and 2007, who underwent either BCT (lumpectomy and radiation treatment) or mastectomy. Multivariable and matched pair analyses were performed to compare overall survival (OS) and cause-specific survival (CSS) of patients undergoing BCT and mastectomy. RESULTS: A total of 14,764 women were identified, of whom 45% received BCT and 55% received mastectomy. Median follow-up was 5.7 years (range, 0.5-17.9 years). After we accounted for all patient and tumor characteristics, multivariable analysis found that BCT resulted in OS (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.83-1.04; p = 0.16) and CSS (HR, 0.93; CI, 0.83-1.05; p = 0.26) similar to that of mastectomy. Matched pair analysis, including 4,644 BCT and mastectomy patients, confirmed no difference in OS or CSS: the 5-, 10-, and 15-year OS rates for BCT and mastectomy were 92.5%, 83.5%, and 77.0% and 91.9%, 83.6%, and 79.1%, respectively (p = 0.99), and the 5 , 10-, and 15-year CSS rates for BCT and mastectomy were 93.3%, 85.5%, and 79.9% and 92.5%, 85.5%, and 81.9%, respectively (p = 0.88). CONCLUSIONS: Our analysis of this population-based database suggests that young women with early-stage breast cancer have similar survival rates whether treated with BCT or mastectomy. These patients should be counseled appropriately regarding their treatment options and should not choose a mastectomy based on the assumption of improved survival. PMID- 22300562 TI - Adjuvant chemotherapy with or without pelvic radiotherapy after simultaneous surgical resection of rectal cancer with liver metastases: analysis of prognosis and patterns of recurrence. AB - PURPOSE: To investigate the outcomes of adjuvant chemotherapy (CT) or chemoradiotherapy (CRT) after simultaneous surgical resection in rectal cancer patients with liver metastases (LM). MATERIALS AND METHODS: One hundred and eight patients receiving total mesorectal excision for rectal cancer and surgical resection for LM were reviewed. Forty-eight patients received adjuvant CRT, and 60 were administered CT alone. Recurrence patterns and prognosis were analyzed. Disease-free survival (DFS) and overall survival (OS) rates were compared between the CRT and CT groups. The inverse probability of the treatment-weighted (IPTW) method based on the propensity score was used to adjust for selection bias between the two groups. RESULTS: At a median follow-up period of 47.7 months, 77 (71.3%) patients had developed recurrences. The majority of recurrences (68.8%) occurred in distant organs. By contrast, the local recurrence rate was only 4.7%. Median DFS and OS were not significantly different between the CRT and CT groups. After applying the IPTW method, we observed no significant differences in terms of DFS (hazard ratio [HR], 1.347; 95% confidence interval [CI], 0.759-2.392; p = 0.309) and OS (HR, 1.413; CI, 0.752-2.653; p = 0.282). Multivariate analyses showed that unilobar distribution of LM and normal preoperative carcinoembryonic antigen level (<6 mg/mL) were significantly associated with longer DFS and OS. CONCLUSIONS: The local recurrence rate after simultaneous resection of rectal cancer with LM was relatively low. DFS and OS rates were not different between the adjuvant CRT and CT groups. Adjuvant CRT may have a limited role in this setting. Further prospective randomized studies are required to evaluate optimal adjuvant treatment in these patients. PMID- 22300563 TI - Long-term outcomes after high-dose postprostatectomy salvage radiation treatment. AB - PURPOSE: To review the impact of high-dose radiotherapy (RT) in the postprostatectomy salvage setting on long-term biochemical control and distant metastases-free survival, and to identify clinical and pathologic predictors of outcomes. METHODS AND MATERIALS: During 1988-2007, 285 consecutive patients were treated with salvage RT (SRT) after radical prostatectomy. All patients were treated with either three-dimensional conformal RT or intensity-modulated RT. Two hundred seventy patients (95%) were treated to a dose >=66 Gy, of whom 205 (72%) received doses >=70 Gy. Eighty-seven patients (31%) received androgen-deprivation therapy as a component of their salvage treatment. All clinical and pathologic records were reviewed to identify treatment risk factors and response. RESULTS: The median follow-up time after SRT was 60 months. Seven-year actuarial prostate specific antigen (PSA) relapse-free survival and distant metastases-free survival were 37% and 77%, respectively. Independent predictors of biochemical recurrence were vascular invasion (p < 0.01), negative surgical margins (p < 0.01), presalvage PSA level >0.4 ng/mL (p < 0.01), androgen-deprivation therapy (p = 0.03), Gleason score >=7 (p = 0.02), and seminal vesicle involvement (p = 0.05). Salvage RT dose >=70 Gy was not associated with improvement in biochemical control. A doubling time <3 months was the only independent predictor of metastatic disease (p < 0.01). There was a trend suggesting benefit of SRT dose >=70 Gy in preventing clinical local failure in patients with radiographically visible local disease at time of SRT (7 years: 90% vs. 79.1%, p = 0.07). CONCLUSION: Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in patients with greater burden of disease at time of SRT as reflected by either radiographic imaging or a greater PSA level. Salvage radiation doses >=70 Gy may ultimately be most beneficial in these patients, but this needs to be further studied. PMID- 22300564 TI - Decreased risk of radiation pneumonitis with incidental concurrent use of angiotensin-converting enzyme inhibitors and thoracic radiation therapy. AB - PURPOSE: Angiotensin-converting enzyme (ACE) inhibitors have been shown to mitigate radiation-induced lung injury in preclinical models. The aim of this study was to evaluate whether ACE inhibitors decrease the risk of radiation pneumonitis in lung cancer patients receiving thoracic irradiation. METHODS AND MATERIALS: Patients with Stage I through III small-cell and non-small-cell lung cancer treated definitively with radiation from 2004-2009 at the Clement J. Zablocki Veterans Affairs Medical Center were retrospectively reviewed. Acute pulmonary toxicity was quantified within 6 months of completion of treatment according to the Common Terminology Criteria for Adverse Events version 4. The use of ACE inhibitors, nonsteroidal anti-inflammatory drugs, inhaled glucocorticosteroids, statins, and angiotensin receptor blockers; dose-volume histogram parameters; and patient factors were assessed for association with Grade 2 or higher pneumonitis. RESULTS: A total of 162 patients met the criteria for inclusion. The majority of patients had Stage III disease (64%) and received concurrent chemotherapy (61%). Sixty-two patients were identified as ACE inhibitor users (38%). All patients had acceptable radiation plans based on dose volume histogram constraints (V20 [volume of lung receiving at least 20 Gy] <=37% and mean lung dose <=20 Gy) with the exception of 2 patients who did not meet both criteria. Grade 2 or higher pulmonary toxicity occurred in 12 patients (7.4%). The rate of Grade 2 or higher pneumonitis was lower in ACE inhibitor users vs. nonusers (2% vs. 11%, p = 0.032). Rates of Grade 2 or higher pneumonitis were significantly increased in patients aged greater than 70 years (16% vs. 2%, p = 0.005) or in whom V5 (volume of lung receiving at least 5 Gy) was 50% or greater (13% vs. 4%, p = 0.04). V10 (volume of lung receiving at least 10 Gy), V20, V30 (volume of lung receiving at least 30 Gy), and mean lung dose were not independently associated with Grade 2 or higher pneumonitis. CONCLUSION: ACE inhibitors may decrease the incidence of radiation pneumonitis in patients receiving thoracic radiation for lung cancer. These findings are consistent with preclinical evidence and should be prospectively evaluated. PMID- 22300565 TI - Outcome and prognostic factors in endometrial stromal tumors: a Rare Cancer Network study. AB - PURPOSE: To provide further understanding regarding outcome and prognostic factors of endometrial stromal tumors (EST). METHODS AND MATERIALS: A retrospective analysis was performed on the records of 59 women diagnosed with EST and treated with curative intent between 1983 and 2007 in the framework of the Rare Cancer Network. RESULTS: Endometrial stromal sarcomas (ESS) were found in 44% and undifferentiated ESS (UES) in 49% of the cases. In 7% the grading was unclear. Of the total number of patients, 33 had Stage I, 4 Stage II, 20 Stage III, and 1 presented with Stage IVB disease. Adjuvant chemotherapy was administered to 12 patients, all with UES. External-beam radiotherapy (RT) was administered postoperatively to 48 women. The median follow-up was 41.4 months. The 5-year overall survival (OS) rate was 96.2% and 64.8% for ESS and UES, respectively, with a corresponding 5-year disease-free survival (DFS) rate of 49.4% and 43.4%, respectively. On multivariate analysis, adjuvant RT was an independent prognostic factor for OS (p = 0.007) and DFS (p = 0.013). Locoregional control, DFS, and OS were significantly associated with age (<=60 vs. >60 years), grade (ESS vs. UES), and International Federation of Gynecology and Obstetrics stage (I-II vs. III-IV). Positive lymph node staging had an impact on OS (p < 0.001). CONCLUSION: The prognosis of ESS differed from that of UES. Endometrial stromal sarcomas had an excellent 5-year OS, whereas the OS in UES was rather low. However, half of ESS patients had a relapse. For this reason, adjuvant treatment such as RT should be considered even in low-grade tumors. Multicenter randomized studies are still warranted to establish clear guidelines. PMID- 22300566 TI - Quality assurance of multifractionated pelvic interstitial brachytherapy for postoperative recurrences of cervical cancers: a prospective study. AB - PURPOSE: To evaluate three-dimensional needle displacements during multifractionated interstitial brachytherapy (BT) for cervical cancers. METHODS AND MATERIALS: Patients scheduled to undergo pelvic interstitial BT for postoperative and or postradiation vault recurrences were included from November 2009 to December 2010. All procedures were performed under spinal anesthesia. Postprocedure BT planning CT scans were obtained with patients in supine position with arms on the chest (interslice thickness of 3 mm). Thereafter, verification CT was repeated at every alternate fraction. Needle displacements were measured in reference to a relocatable bony point. The mean cranial, caudal, anteroposterior, and mediolateral displacements were recorded. Statistical significance of mean interfraction displacements was evaluated with Wilcoxon Test. RESULTS: Twenty patients were included. Seventeen received boost BT (20 Gy/5 fractions/3 days) after external radiation, three received radical BT alone (36 Gy/9 fractions/5-8 days). An average of three scans (range, 2-3) were available per patient, and 357 needle displacements were analyzed. For the entire study cohort, the average of mean needle displacement was 2.5 mm (range, 0-7.4), 17.4 mm (range, 0-27.9), 1.7 mm (range, 0-6.7), 2.1 mm (range, 0-9.5), 1.7 mm (range, 0-9.3), and 0.6 mm (range, 0-7.8) in cranial, caudal, anterior, posterior, right, and left directions, respectively. The mean displacement in the caudal direction was higher between Days 1 and 2 than that between Days 2 and 3 (13.4 mm vs. 3.8 mm; p = 0.01). The average caudal displacements were no different between reirradiation and boost cohort (15.2 vs. 17.8 mm). CONCLUSIONS: Clinically significant caudal displacements occur during multifractionated pelvic brachytherapy. Optimal margins need to be incorporated while preplanning brachytherapy to account for interfraction displacements. PMID- 22300567 TI - Predicting rectal and bladder overdose during the course of prostate radiotherapy using dose-volume data from initial treatment fractions. AB - PURPOSE: To evaluate whether information from the initial fractions can determine which patients are likely to consistently exceed their planning dose-volume constraints during the course of radiotherapy for prostate cancer. METHODS AND MATERIALS: Ten patients with high-risk prostate cancer were treated with helical tomotherapy to a dose of 60 Gy in 20 fractions. The prostate, rectum, and bladder were recontoured on their daily megavoltage computed tomography scans and the dose was recalculated. The bladder and rectal volumes (in mL) receiving >=100% and >=70% of the prescribed dose in each fraction and in the original plans were recorded. A fraction for which the difference between planned and delivered was more than 2 mL was considered a volume failure. Similarly if the difference in the planned and delivered maximum dose (D(max)) was >=1% for the rectum and bladder, the fraction was considered a dose failure. Each patient's first 3 to 5 fractions were analyzed to determine if they correctly identified those patients who would consistently fail (i.e., >=20% of fractions) during the course of their radiotherapy. RESULTS: Six parameters were studied; the rectal volume (RV) and bladder volumes (BV) (in mL) received >=100% and >=70% of the prescribed dose and maximum dose to 2 mL of the rectum and bladder. This was given by RV100, RV70, BV100, BV70, RD(max), and BD(max), respectively. When more than 1 of the first 3 fractions exceed the planning constraint as defined, it accurately predicts consistent failures through the course of the treatment. This method is able to correctly identify the consistent failures about 80% (RV70, BV100, and RV100), 90% (BV70), and 100% (RD(max) and BD(max)) of the times. CONCLUSIONS: This study demonstrates the feasibility of a method accurately identifying patients who are likely to consistently exceed the planning constraints during the course of their treatment, using information from the first 3 to 5 fractions. PMID- 22300568 TI - Effectiveness of reirradiation for painful bone metastases: a systematic review and meta-analysis. AB - PURPOSE: Reirradiation of painful bone metastases in nonresponders or patients with recurrent pain after initial response is performed in up to 42% of patients initially treated with radiotherapy. Literature on the effect of reirradiation for pain control in those patients is scarce. In this systematic review and meta analysis, we quantify the effectiveness of reirradiation for achieving pain control in patients with painful bone metastases. METHODS AND MATERIALS: A free text search was performed to identify eligible studies using the MEDLINE, EMBASE, and the Cochrane Collaboration library electronic databases. After study selection and quality assessment, a pooled estimate was calculated for overall pain response for reirradiation of metastatic bone pain. RESULTS: Our literature search identified 707 titles, of which 10 articles were selected for systematic review and seven entered the meta-analysis. Overall study quality was mediocre. Of the 2,694 patients initially treated for metastatic bone pain, 527 (20%) patients underwent reirradiation. Overall, a pain response after reirradiation was achieved in 58% of patients (pooled overall response rate 0.58, 95% confidence interval = 0.49-0.67). There was a substantial between-study heterogeneity (I2 = 63.3%, p = 0.01) because of clinical and methodological differences between studies. CONCLUSIONS: Reirradiation of painful bone metastases is effective in terms of pain relief for a small majority of patients; approximately 40% of patients do not benefit from reirradiation. Although the validity of results is limited, this meta-analysis provides a comprehensive overview and the most quantitative estimate of reirradiation effectiveness to date. PMID- 22300569 TI - Prognostic value of subclassification using MRI in the t4 classification nasopharyngeal carcinoma intensity-modulated radiotherapy treatment. AB - PURPOSE: To subclassify patients with the T4 classification nasopharyngeal carcinoma (NPC), according to the seventh edition of the American Joint Committee on Cancer staging system, using magnetic resonance imaging (MRI), and to evaluate the prognostic value of subclassification after intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: A total of 140 patients who underwent MRI and were subsequently histologically diagnosed with nondisseminated classification T4 NPC received IMRT as their primary treatment and were included in this retrospective study. T4 patients were subclassified into two grades: T4a was defined as a primary nasopharyngeal tumor with involvement of the masticator space only; and T4b was defined as involvement of the intracranial region, cranial nerves, and/or orbit. RESULTS: The 5-year overall survival (OS) rate and distant metastasis-free survival (DMFS) rate for T4a patients (82.5% and 87.0%, respectively), were significantly higher than for T4b patients (62.6% and 66.8%; p = 0.033 and p = 0.036, respectively). The T4a/b subclassification was an independent prognostic factor for OS (hazard ratio = 2.331, p = 0.032) and DMFS (hazard ratio = 2.602, p = 0.034), and had no significant effect on local relapse-free survival. CONCLUSIONS: Subclassification of T4 patients, as T4a or T4b, using MRI according to the site of invasion, has prognostic value for the outcomes of IMRT treatment in NPC. PMID- 22300570 TI - MRI-based preplanning using CT and MRI data fusion in patients with cervical cancer treated with 3D-based brachytherapy: feasibility and accuracy study. AB - PURPOSE: Magnetic resonance imaging (MRI)-assisted radiation treatment planning enables enhanced target contouring. The purpose of this study is to analyze the feasibility and accuracy of computed tomography (CT) and MRI data fusion for MRI based treatment planning in an institution where an MRI scanner is not available in the radiotherapy department. METHODS AND MATERIALS: The registration inaccuracy of applicators and soft tissue was assessed in 42 applications with CT/MRI data fusion. The absolute positional difference of the center of the applicators was measured in four different planes from the top of the tandem to the cervix. Any inaccuracy of registration of soft tissue in relation to the position of applicators was determined and dose-volume parameters for MRI preplans and for CT/MRI fusion plans with or without target and organs at risk (OAR) adaptation were evaluated. RESULTS: We performed 6,132 measurements in 42 CT/MRI image fusions. Median absolute difference of the center of tandem on CT and MRI was 1.1 mm. Median distance between the center of the right ovoid on CT and MRI was 1.7 and 1.9 mm in the laterolateral and anteroposterior direction, respectively. Corresponding values for the left ovoid were 1.6 and 1.8 mm. Rotation of applicators was 3.1 degrees . Median absolute difference in position of applicators in relation to soft tissue was 1.93, 1.50, 1.05, and 0.84 mm in the respective transverse planes, and 1.17, 1.28, 1.27, and 1.17 mm in selected angular directions. The dosimetric parameters for organs at risk on CT/MRI fusion plans without OAR adaptation were significantly impaired whereas the target coverage was not influenced. Planning without target adaptation led to overdosing of the target volume, especially high-risk clinical target volume--D90 88.2 vs. 83.1 (p < 0.05). CONCLUSIONS: MRI-based preplanning with consecutive CT/MRI data fusion can be safe and feasible, with an acceptable inaccuracy of soft tissue registration. PMID- 22300571 TI - In vivo dosimetry for single-fraction targeted intraoperative radiotherapy (TARGIT) for breast cancer. AB - PURPOSE: In vivo dosimetry provides an independent check of delivered dose and gives confidence in the introduction or consistency of radiotherapy techniques. Single-fraction intraoperative radiotherapy of the breast can be performed with the Intrabeam compact, mobile 50 kV x-ray source (Carl Zeiss Surgical, Oberkochen, Germany). Thermoluminescent dosimeters (TLDs) can be used to estimate skin doses during these treatments. METHODS AND MATERIALS: Measurements of skin doses were taken using TLDs for 72 patients over 3 years of clinical treatments. Phantom studies were also undertaken to assess the uncertainties resulting from changes in beam quality and backscatter conditions in vivo. RESULTS: The mean measured skin dose was 2.9 +/- 1.6 Gy, with 11% of readings higher than the prescription dose of 6 Gy, but none of these patients showed increased complications. Uncertainties due to beam hardening and backscatter reduction were small compared with overall accuracy. CONCLUSIONS: TLDs are a useful and effective method to measure in vivo skin doses in intraoperative radiotherapy and are recommended for the initial validation or any modification to the delivery of this technique. They are also an effective tool to show consistent and safe delivery on a more frequent basis or to determine doses to other critical structures as required. PMID- 22300572 TI - Intensity-modulated radiotherapy is associated with improved global quality of life among long-term survivors of head-and-neck cancer. AB - PURPOSE: To compare the long-term quality of life among patients treated with and without intensity-modulated radiotherapy (IMRT) for head-and-neck cancer. METHODS AND MATERIALS: The University of Washington Quality of Life instrument scores were reviewed for 155 patients previously treated with radiation therapy for locally advanced head-and-neck cancer. All patients were disease free and had at least 2 years of follow-up. Eighty-four patients (54%) were treated with IMRT. The remaining 71 patients (46%) were treated with three-dimensional conformal radiotherapy (3D CRT) by use of initial opposed lateral fields matched to a low anterior neck field. RESULTS: The mean global quality of life scores were 67.5 and 80.1 for the IMRT patients at 1 and 2 years, respectively, compared with 55.4 and 57.0 for the 3D CRT patients, respectively (p < 0.001). At 1 year after the completion of radiation therapy, the proportion of patients who rated their global quality of life as "very good" or "outstanding" was 51% and 41% among patients treated by IMRT and 3DCRT, respectively (p = 0.11). At 2 years, the corresponding percentages increased to 73% and 49%, respectively (p < 0.001). On multivariate analysis accounting for sex, age, radiation intent (definitive vs. postoperative), radiation dose, T stage, primary site, use of concurrent chemotherapy, and neck dissection, the use of IMRT was the only variable independently associated with improved quality of life (p = 0.01). CONCLUSION: The early quality of life improvements associated with IMRT not only are maintained but apparently become more magnified over time. These data provide powerful evidence attesting to the long-term benefits of IMRT for head-and-neck cancer. PMID- 22300573 TI - The number of high-risk factors and the risk of prostate cancer-specific mortality after brachytherapy: implications for treatment selection. AB - PURPOSE: To determine whether an increasing number of high-risk factors is associated with higher prostate cancer-specific mortality (PCSM) among men treated with brachytherapy (BT)-based treatment, and whether supplemental therapy has an impact on this risk. METHODS AND MATERIALS: We analyzed the cases of 2234 men with localized prostate cancer treated between 1991 and 2007 with low-dose rate BT monotherapy (n = 457) or BT with supplemental external-beam radiotherapy (EBRT, n = 229), androgen suppression therapy (AST, n = 424), or both (n = 1124). All men had at least one high-risk factor (prostate-specific antigen >20 ng/mL, biopsy Gleason score 8-10, or clinical stage >=T2c). Competing-risks multivariable regressions were performed to determine whether the presence of at least two high-risk factors was associated with an increased risk of PCSM, with adjustment for age, comorbidity, and the type of supplemental treatment. RESULTS: The median follow-up time was 4.3 years. The number of men with at least two high risk factors was highest in the group treated with BT, EBRT, and AST (21%), followed by BT plus EBRT or AST (13%), and BT alone (8%) (p(trend) < 0.001). The adjusted hazard ratio (AHR) for PCSM for those with at least two high-risk factors (as compared with one) was 4.8 (95% confidence interval [CI], 2.8-8.0; p < 0.001). The use of both supplemental EBRT and AST was associated with a decreased risk of PCSM (AHR 0.5; 95% CI, 0.2-0.9; p = 0.03) compared with BT alone. When the high-risk factors were analyzed separately, Gleason score 8-10 was most significantly associated with increased PCSM (AHR 6.2; 95% CI, 3.5-11.2; p < 0.001). CONCLUSIONS: Men with high-risk prostate adenocarcinoma treated with BT have decreased PCSM if they receive trimodailty therapy that includes EBRT and AST. This benefit is likely most important in men with multiple determinants of high risk. PMID- 22300574 TI - Radiation dose to the brachial plexus in head-and-neck intensity-modulated radiation therapy and its relationship to tumor and nodal stage. AB - PURPOSE: The purpose of this retrospective study was to determine tumor factors contributing to brachial plexus (BP) dose in head-and-neck cancer (HNC) patients treated with intensity-modulated radiotherapy (IMRT) when the BP is routinely contoured as an organ at risk (OAR) for IMRT optimization. METHODS AND MATERIALS: From 2004 to 2011, a total of 114 HNC patients underwent IMRT to a total dose of 69.96 Gy in 33 fractions, with the right and left BP prospectively contoured as separate OARs in 111 patients and the ipsilateral BP contoured in 3 patients (total, 225 BP). Staging category T4 and N2/3 disease were present in 34 (29.8%) and 74 (64.9%) patients, respectively. During IMRT optimization, the intent was to keep the maximum BP dose to <=60 Gy, but prioritizing tumor coverage over achieving the BP constraints. BP dose parameters were compared with tumor and nodal stage. RESULTS: With a median follow-up of 16.2 months, 43 (37.7%) patients had >=24 months of follow-up with no brachial plexopathy reported. Mean BP volume was 8.2 +/- 4.5 cm(3). Mean BP maximum dose was 58.1 +/- 12.2 Gy, and BP mean dose was 42.2 +/- 11.3 Gy. The BP maximum dose was <=60, <=66, and <=70 Gy in 122 (54.2%), 185 (82.2%), and 203 (90.2%) BP, respectively. For oropharynx, hypopharynx, and larynx sites, the mean BP maximum dose was 58.4 Gy and 63.4 Gy in T0-3 and T4 disease, respectively (p = 0.002). Mean BP maximum dose with N0/1 and N2/3 disease was 52.8 Gy and 60.9 Gy, respectively (p < 0.0001). CONCLUSIONS: In head-and-neck IMRT, dose constraints for the BP are difficult to achieve to <=60 to 66 Gy with T4 disease of the larynx, hypopharynx, and oropharynx or N2/3 disease. The risk of brachial plexopathy is likely very small in HNC patients undergoing IMRT, although longer follow-up is required. PMID- 22300575 TI - Critical appraisal of Acuros XB and Anisotropic Analytic Algorithm dose calculation in advanced non-small-cell lung cancer treatments. AB - PURPOSE: To assess the clinical impact of the Acuros XB algorithm (implemented in the Varian Eclipse treatment-planning system) in non-small-cell lung cancer (NSCLC) cases. METHODS AND MATERIALS: A CT dataset of 10 patients presenting with advanced NSCLC was selected and contoured for planning target volume, lungs, heart, and spinal cord. Plans were created for 6-MV and 15-MV beams using three dimensional conformal therapy, intensity-modulated therapy, and volumetric modulated arc therapy with RapidArc. Calculations were performed with Acuros XB and the Anisotropic Analytical Algorithm. To distinguish between differences coming from the different heterogeneity management and those coming from the algorithm and its implementation, all the plans were recalculated assigning Hounsfield Unit (HU) = 0 (Water) to the CT dataset. RESULTS: Differences in dose distributions between the two algorithms calculated in Water were <0.5%. This suggests that the differences in the real CT dataset can be ascribed mainly to the different heterogeneity management, which is proven to be more accurate in the Acuros XB calculations. The planning target dose difference was stratified between the target in soft tissue, where the mean dose was found to be lower for Acuros XB, with a range of 0.4% +/- 0.6% (intensity-modulated therapy, 6 MV) to 1.7% +/- 0.2% (three-dimensional conformal therapy, 6 MV), and the target in lung tissue, where the mean dose was higher for 6 MV (from 0.2% +/- 0.2% to 1.2% +/- 0.5%) and lower for 15 MV (from 0.5% +/- 0.5% to 2.0% +/- 0.9%). Mean doses to organs at risk presented differences up to 3% of the mean structure dose in the worst case. No particular or systematic differences were found related to the various modalities. Calculation time ratios between calculation time for Acuros XB and the Anisotropic Analytical Algorithm were 7 for three-dimensional conformal therapy, 5 for intensity-modulated therapy, and 0.2 for volumetric modulated arc therapy with RapidArc. CONCLUSION: The availability of Acuros XB could improve patient dose estimation, increasing the data consistency of clinical trials. PMID- 22300576 TI - Large-scale isotype-specific quantification of Serum amyloid A 1/2 by multiple reaction monitoring in crude sera. AB - Quantification is an essential step in biomarker development. Multiple reaction monitoring (MRM) is a new modified mass spectrometry-based quantification technology that does not require antibody development. Serum amyloid A (SAA) is a positive acute-phase protein identified as a lung cancer biomarker in our previous study. Acute SAA exists in two isoforms with highly similar (92%) amino acid sequences. Until now, studies of SAA have been unable to distinguish between SAA1 and SAA2. To overcome the unavailability of a SAA2-specific antibody, we developed MRM methodology for the verification of SAA1 and SAA2 in clinical crude serum samples from 99 healthy controls and 100 lung adenocarcinoma patients. Differential measurement of SAA1 and SAA2 was made possible for the first time with the developed isotype-specific MRM method. Most healthy control samples had small or no MS/MS peaks of the targeted peptides otherwise, higher peak areas with 10- to 34-fold increase over controls were detected in lung cancer samples. In addition, our SAA1 MRM data demonstrated good agreement with the SAA1 enzyme linked immunosorbent assay (ELISA) data. Finally, successful quantification of SAA2 in crude serum by MRM, for the first time, shows that SAA2 can be a good biomarker for the detection of lung cancers. PMID- 22300577 TI - Exploring the proteomes of the venoms of the Peruvian pit vipers Bothrops atrox, B. barnetti and B. pictus. AB - We report the comparative proteomic characterization of the venoms of Bothrops atrox, B. barnetti and B. pictus. The venoms were subjected to RP-HPLC and the resulting fractions analyzed by SDS-PAGE. The proteins were cut from the gels, digested with trypsin and identified via peptide mass fingerprint and manual sequencing of selected peptides by MALDI-TOF/TOF mass spectrometry. Around 20-25 proteins were identified belonging to only 6-7 protein families. Metalloproteinases of the classes P-I and P-III were the most abundant proteins in all venoms (58-74% based on peak area A214 nm), followed by phospholipases A(2) (6.4-14%), disintegrins (3.2-9%) and serine proteinases (7-11%), and some of these proteins occurred in several isoforms. In contrast cysteine-rich secretory proteins and L-amino acid oxidases appeared only as single isoforms and were found only in B. atrox and B. barnetti. C-type lectins were also detected in all venoms but at low levels (~ 5%). Furthermore, the venoms contain variable numbers of peptides (<3 kDa) and non-protein compounds which were not considered in this work. The protein composition of the investigated Bothrops species is in agreement with their pharmacological and pathological effects. PMID- 22300578 TI - Characterization of the glycated human cerebrospinal fluid proteome. AB - Protein glycation is a nonenzymatic modification that involves pathological functions in neurological diseases. Despite the high number of studies showing accumulation of advanced end glycation products (AGEs) at clinical stage, there is a lack of knowledge about which proteins are modified, where those modifications occur, and to what extent. The goal of this study was to achieve a comprehensive characterization of proteins modified by early glycation in human cerebrospinal fluid (CSF). Approaches based on glucose diferential labeling and mass spectrometry have been applied to evaluate the glycated CSF proteome at two physiological conditions: native glucose level and in vitro high glucose content. For both purposes, detection of glycated proteins was carried out by HCD-MS2 and CID-MS3 modes after endoproteinase Glu-C digestion and boronate affinity chromatography. The abundance of glycation was assessed by protein labeling with (13)C(6)-glucose incubation. The analysis of native glycated CSF identified 111 glycation sites corresponding to 48 glycated proteins. Additionally, the in vitro high glucose level approach detected 265 glycation sites and 101 glycated proteins. The comparison of glycation levels under native and 15 mM glucose conditions showed relative concentration increases up to ten folds for some glycated proteins. This report revealed for the first time a number of key glycated CSF proteins known to be involved in neuroinflammation and neurodegenerative disorders. Altogether, the present study contains valuable and unique information, which should further help to clarify the pathological role of glycation in central nervous system pathologies. This article is part of a Special Issue entitled: Translational Proteomics. PMID- 22300579 TI - Quantitative analysis of proteins in the tear fluid of patients with diabetic retinopathy. AB - Diabetic retinopathy is the leading cause of new cases of legal blindness among adults in the developed countries. Approximately 40% of all people with diabetes have diabetic retinopathy and 5% of these have sight-threatening form. As the advanced stage, where there is a high risk for vision loss, can develop without any serious symptoms, sometimes it is hard to detect it. A non invasive method to detect biomarkers characteristic for diabetic retinopathy from the tear fluid was developed. Tear samples from diabetic patients with no retinopathy, non proliferative and proliferative stages of diabetic retinopathy were analyzed and the protein content of each sample was compared to the protein content of tear pool from healthy volunteers. The samples were labeled with iTRAQ fourplex labels and were analyzed with nanoHPLC coupled ESI-MS/MS mass spectrometry. The lipocalin 1, lactotransferrin, lacritin, lysozyme C, lipophilin A and immunoglobulin lambda chain were identified as possible biomarker candidates with significantly higher relative levels in the tear of patients with diabetic retinopathy. PMID- 22300580 TI - Assessment of the humoral immune response to cancer. AB - One of the deadly hallmarks of cancer is its ability to prosper within the constraints of the host immune system. Recent advances in immunoproteomics and high-throughput technologies have lead to profiling of the antibody repertoire in cancer patients. This in turn has lead to the identification of tumour associated antigens/autoantibodies. Autoantibodies are extremely attractive and promising biomarker entities, however there has been relatively little discussion on how to interpret the humoral immune response. It may be that autoantibody profiles hold the key to ultimately uncovering neoplastic associated pathways and through the process of immunosculpting the tumour may have yielded an immune response in the early stages of malignant tumour development. The aim of this review is to discuss the utility of the autoantibody response that is elicited as a result of malignancy and discuss the advantages and limitations of autoantibody profiling. This article is part of a Special Issue entitled: Translational Proteomics. PMID- 22300581 TI - Livestock-associated MRSA prevalence in veal calf production is associated with farm hygiene, use of antimicrobials, and age of the calves. AB - Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is highly prevalent in pork and veal production chains. In this study, we used data from a cross-sectional survey on 2151 calves from 102 veal calf farms to identify potential risk factors, with the goal of reducing MRSA prevalence by developing intervention strategies. Overall, calves from rose veal farms had a lower risk of LA-MRSA carriage than calves from white veal farms. Data were analysed separately for white and rose veal calves, because management systems of the two production chains were largely different. Group treatment with antimicrobials appeared to be a risk factor for MRSA carriage in white veal calves in univariate analyses, but was not included in the final multiple regression model that included age of the calves and rodent control. Number of start treatment days was positively associated with LA-MRSA carriage in rose veal calves, and was the only risk factor selected for the final multiple regression model for this group. Interpretation of the results from this cross-sectional study is complicated by the strong correlation between antimicrobial use, LA-MRSA carriage and age of the calves. Other age-related factors may be more influential. However, taken together these findings emphasize the need for prudent use of antimicrobials, and point to improvement of farm hygiene as a control measure. PMID- 22300582 TI - Ventilatory mechanics from maniraptoran theropods to extant birds. AB - Shared behavioural, morphological and physiological characteristics are indicative of the evolution of extant birds from nonavian maniraptoran dinosaurs. One such shared character is the presence of uncinate processes and respiratory structures in extant birds. Recent research has suggested a respiratory role for these processes found in oviraptorid and dromaeosaurid dinosaurs. By measuring the geometry of fossil rib cage morphology, we demonstrate that the mechanical advantage, conferred by uncinate processes, for movements of the ribs in the oviraptorid theropod dinosaur, Citipati osmolskae, basal avialan species Zhongjianornis yangi, Confuciusornis sanctus and the more derived ornithurine Yixianornis grabaui, is of the same magnitude as found in extant birds. These skeletal characteristics provide further evidence of a flow-through respiratory system in nonavian theropod dinosaurs and basal avialans, and indicate that uncinate processes are a key adaptation facilitating the ventilation of a lung air sac system that diverged earlier than extant birds. PMID- 22300583 TI - Rudhira/BCAS3 is a cytoskeletal protein that controls Cdc42 activation and directional cell migration during angiogenesis. AB - Cell migration is a common cellular process in angiogenesis and tumor metastasis. Rudhira/BCAS3 (Breast Cancer Amplified Sequence 3) is a conserved protein expressed in the embryonic vasculature and malignant tumors. Here, we show for the first time that Rudhira plays an active role in directional cell migration. Rudhira depletion in endothelial cells inhibits Matrigel-induced tube formation and retards healing of wounded cell monolayers. We demonstrate that during wound healing, Rudhira rapidly re-localizes and promotes Cdc42 activation and recruitment to the leading edge of migrating cells. Rudhira deficient cells show impaired downstream signaling of Cdc42 leading to dramatic changes in actin organization and classic cell polarity defects such as loss of microtubule organizing center (MTOC) and Golgi re-orientation. Biochemical assays and co localization studies show that Rudhira interacts with microtubules as well as intermediate filaments. Thus, Rudhira could control directional cell migration and angiogenesis by facilitating crosstalk between cytoskeletal elements. PMID- 22300584 TI - Identification of an emerging recombinant cluster in porcine circovirus type 2. AB - Porcine circovirus type 2 (PCV2) is continuously evolving through point mutation and genome recombination. In the present study, genetic affiliations of 40 PCV2 strains were determined by amplification, sequencing and phylogenetic analyses during the nationwide molecular epidemiology investigation from 2009 to 2010 in mainland China. The results revealed that PCV2b was the predominant genotype in mainland China from 2009 to 2010 and PCV2b-1C within PCV-2b genotype was an emerging predominant subtype. More interestingly, five strains (09HaiN-1, 09HaiN 2, 10AH, 10GX and 10QH) were classified into a novel cluster along with the two main PCV2 genotypes PCV2a and PCV2b. Further analyses revealed that this novel cluster arose from recombination between PCV2a and PCV2b stains within the ORF2 gene. Moreover, BLAST search on NCBI website revealed that PCV2 strains of the novel cluster also emerged in Thailand, Indonesia and Laos, indicating that the novel cluster of PCV2 has also been circulating in some other Asian countries. This study is the first time to perform comprehensive analyses to demonstrate a cluster of PCV2 strains derived from the same type of inter-genotypic recombination pattern. Our findings provide valuable information on PCV2 evolution. PMID- 22300585 TI - Conservation and divergence of chemical defense system in the tunicate Oikopleura dioica revealed by genome wide response to two xenobiotics. AB - BACKGROUND: Animals have developed extensive mechanisms of response to xenobiotic chemical attacks. Although recent genome surveys have suggested a broad conservation of the chemical defensome across metazoans, global gene expression responses to xenobiotics have not been well investigated in most invertebrates. Here, we performed genome survey for key defensome genes in Oikopleura dioica genome, and explored genome-wide gene expression using high density tiling arrays with over 2 million probes, in response to two model xenobiotic chemicals - the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) the pharmaceutical compound Clofibrate (Clo). RESULTS: Oikopleura genome surveys for key genes of the chemical defensome suggested a reduced repertoire. Not more than 23 cytochrome P450 (CYP) genes could be identified, and neither CYP1 family genes nor their transcriptional activator AhR was detected. These two genes were present in deuterostome ancestors. As in vertebrates, the genotoxic compound BaP induced xenobiotic biotransformation and oxidative stress responsive genes. Notable exceptions were genes of the aryl hydrocarbon receptor (AhR) signaling pathway. Clo also affected the expression of many biotransformation genes and markedly repressed genes involved in energy metabolism and muscle contraction pathways. CONCLUSIONS: Oikopleura has the smallest number of CYP genes among sequenced animal genomes and lacks the AhR signaling pathway. However it appears to have basic xenobiotic inducible biotransformation genes such as a conserved genotoxic stress response gene set. Our genome survey and expression study does not support a role of AhR signaling pathway in the chemical defense of metazoans prior to the emergence of vertebrates. PMID- 22300586 TI - Role of physicochemical characteristics in the uptake of TiO2 nanoparticles by fibroblasts. AB - The relation between the physico-chemical properties of nanoparticles (NPs) and the degree of cellular uptake is incompletely elucidated. In this study, we investigated the influence on the cellular uptake of a wide range of fully characterized TiO2 NPs. L929 fibroblasts were exposed for 24 h to clinically relevant concentrations of nano-TiO2 and the degree of their association was assessed by ultrahigh resolution imaging microscopy (URI), scanning (SEM) and transmission (TEM) electron microscopy, as well as inductivity coupled plasma mass spectroscopy (ICP-MS). The role of actin polymerization, a central feature of active internalization, was also studied and the results indicated that the internalization of TiO2 NPs involves a combination of actin-dependent uptake of large agglomerates as well as non actin-dependent uptake of small agglomerates. SEM and TEM revealed that the agglomerates of all NPs types were attached to the cellular membrane as well as internalized and confined inside cytoplasmic vesicles. URI and ICP-MS demonstrated that the particle association with cells was dose-dependent. The highest association was observed for spherical particles having mixed anatase-rutile crystallographic phase and the lowest for spindle shaped rutile particles. ICP-MS revealed that the association was size-dependent in the order 5>10>40 nm for anatase spherical nanoparticles. PMID- 22300587 TI - Determination of 49 organophosphorus pesticide residues and their metabolites in fish, egg, and milk by dual gas chromatography-dual pulse flame photometric detection with gel permeation chromatography cleanup. AB - A new method for the quantitative determination of 49 kinds of organophosphorus pesticide residues and their metabolites in fish, egg, and milk by dual gas chromatography-dual pulse flame photometric detection was developed. Homogenized samples were extracted with acetone and methylene chloride (1 + 1, v/v), and then the extracts were cleaned up by gel permeation chromatography (GPC). The response of each organophosphorus pesticide showed a good linearity with its concentration; the linearity correlation was not less than 0.99. The detection limits (S/N = 3) of pesticides were in the range of 0.001-0.025 mg kg-1. The recovery experiments were performed by blank sample spiked at low, medium, and high fortification levels. The recoveries for fish, egg, and milk were 50.9 142.2, 53.3-137.2, and 50.3-139.4% with relative standard deviations (RSD, n = 6) of 2.3-24.9, 4.3-26.7, and 2.8-32.2%, respectively. The method was applied to detect organophosphorus pesticides in samples collected from the market, and satisfactory results were obtained. This quantitative method was highly sensitive and exact and could be applied to the accurate determination of organophosphorus contaminants in fish, egg, and milk. PMID- 22300589 TI - Save the date for APIC 2012. PMID- 22300588 TI - ERG protein expression reflects hormonal treatment response and is associated with Gleason score and prostate cancer specific mortality. AB - BACKGROUND: ERG (ETS regulated gene) protein expression has been shown to reflect ERG genomic rearrangements in prostate cancer (PCA). However, ERG protein expression prognostic value has not been yet investigated. DESIGN: ERG protein expression was investigated in a cohort of 312 men with PCA diagnosed in transurethral resection of the prostate. RESULTS: ERG expression was detected in 76/293 (25.9%) of patients. Overall ERG expression was associated with Gleason score (GS) (p<0.0001), tumour volume (p=0.04) and with cancer specific mortality (p=0.15). Low ERG intensity was significantly associated with higher GS (p=0.02) and marginally with cancer specific mortality (p=0.11). The association with cancer specific mortality was more significant in patients without any hormonal manipulation (p=0.02). Multivariate Cox model using GS, tumour volume and ERG intensity to predict time to cancer specific death yielded a marginally significant effect for high versus low ERG protein expression (hazard ratio (HR)=0.36; 95% confidence interval (CI): 0.10-1.38; p=0.14) and a non-significant effect for GS >7 (HR=4.85; 95%CI: 0.48, 48.65; p=0.18). Men with ERG expression showed longer free progression time to castration resistant disease compared to men with no ERG expression (mean 11.39 versus 6.1 months, p=0.08). CONCLUSION: We report significant association between ERG protein levels and each of GS, progression to castration resistant and cancer specific mortality. High ERG intensity was associated with lower GS, better overall survival and longer free progression times to castration resistant disease. ERG protein levels may have prognostic and therapeutic role in PCA and should be investigated in future studies. PMID- 22300590 TI - Frequency of outbreak investigations in US hospitals: results of a national survey of infection preventionists. AB - BACKGROUND: A survey of infection preventionists was conducted to determine the frequency of outbreak investigations in US hospitals. METHODS: A 2-part electronic survey was sent to Association for Professionals in Infection Control and Epidemiology, Inc, members in US hospitals in January 2010. Part 1 of the survey tool involved hospital demographics and the infection prevention/control program. Part 2 explored specific outbreak investigations allowing responses for up to 8 investigations within the previous 24 months. RESULTS: A final sample of 822 responses was analyzed representing 386 outbreak investigations in 289 US hospitals. Nearly 60% of the outbreaks were caused by 4 organisms: norovirus (18%), Staphylococcus aureus (17%), Acinetobactor spp (14%), and Clostridium difficile (10%). Norovirus occurred most often in behavioral health and rehabilitation/long-term acute care units, whereas the other organisms occurred in medical/surgical units. Unit/department closure was reported in 22.6% of investigations and most often associated with norovirus. Outbreak investigations are triggered by unusual organisms, rate above baseline for specific site of infection, and rate above baseline for specific unit. Investigations were most frequently conducted in community/nonteaching hospitals and facilities with 201 to 300 beds. Mean number of confirmed cases was 10; mean duration was 58 days. CONCLUSION: Norovirus is emerging as an increasingly common hospital-associated organism causing outbreaks in nonacute settings and may lead to unit/department closures. PMID- 22300591 TI - Patient, center and geographic characteristics of nationally placed livers. AB - Once a liver offer has been refused locally and regionally, it is offered nationally. We characterized nationally (n = 1567) versus locally (n = 19 893) placed grafts from adult, nonfulminant, deceased donor liver transplants (LT) from 2/1/05 to 1/31/10. Donors of nationally versus locally placed livers differed by age (50 vs. 42 years), positive HCV antibody (11 vs. 2%) and death from stroke (51 vs. 42%) (p < 0.001 for all). Recipients of nationally versus locally placed livers differed by LT-MELD (20 vs. 24), rates of ascites (35 vs. 37%), encephalopathy (12 vs. 15%), hepatocellular (17 vs. 24%) and nonhepatocellular exceptions (6 vs. 11%) (p <= 0.03 for all). Six (5%) centers utilized 64% of the nationally placed grafts while 43 (38%) centers accepted zero during the 5-year period; all high volume centers used >=1. Compared to local distribution, transplantation with a nationally placed liver was associated with a similar adjusted risk of graft (HR, 0.99; 95% CI, 0.86-1.14) and patient (HR, 0.98; 95% CI, 0.84-1.14; p = 0.77) survival. In conclusion, utilization of nationally placed livers is highly concentrated in very few centers, with no increased adjusted risk of graft loss. These findings provide the foundation for a more informed discussion about changing our current liver allocation and distribution policies. PMID- 22300592 TI - Statistical and analytical approaches for assessing biomarkers: new approaches, new technologies, with the same-old rigor for evaluation. PMID- 22300593 TI - Quality, and not just quantity, of education accounts for differences in psychometric performance between african americans and white non-hispanics with Alzheimer's disease. AB - The effect of race on cognitive test performance in the evaluation of Alzheimer's disease (AD) remains controversial. One factor that may contribute substantially to differences in cognitive test performance in diverse populations is education. The current study examined the extent to which quality of education, even after controlling for formal years of education, accounts for differences in cognitive performance between African Americans and White Non-Hispanics (WNHs). The retrospective cohort included 244 patients diagnosed with AD who self-identified as African Americans (n = 51) or WNHs (n = 193). The Wechsler Test of Adult Reading (WTAR) was used as an estimate of quality of education. In an analysis that controlled for traditional demographics, including age, sex, and years of formal education, African Americans scored significantly lower than WNHs on the Mini-Mental State Examination, as well as on neuropsychological tests of memory, attention, and language. However, after also adjusting for reading level, all previously observed differences were significantly attenuated. The attenuating effect remained even after controlling for disease severity, indicating that reading scores are not confounded by severity of dementia. These findings suggest that quality, and not just quantity, of education needs to be taken into account when assessing cognitive performance in African Americans with AD. PMID- 22300594 TI - Association between eating out of home and body weight. AB - Eating outside of the home environment on a frequent basis has been associated with weight gain. Food choices when eating out are usually high in energy content, which contributes to excessive energy intake; however, the available data on out-of-home eating and obesity are far from conclusive. This systematic review assesses the association between out-of-home eating and body weight in adults over 18 years of age. The literature databases searched included Medline, Embase, Lilacs, The Cochrane Library, and the ISI Web of Knowledge. The review includes a comprehensive quality assessment of all included observational studies, 20 cross-sectional studies, and 8 prospective cohort studies. All but one of the prospective cohort studies and about half of the cross-sectional analyses found a positive association between out-of-home eating and body weight. However, many methodological differences among the studies were found, such as the definition of out-of-home eating and its assessment, which limits comparisons. The results of the present analysis suggest that in future studies fast-food restaurants and other out-of-home dining venues should be analyzed separately, assessments based on a single 24-h recall should be avoided, and controls for at-home choices (which were not included in any of the studies reviewed) are necessary to evaluate this association. PMID- 22300595 TI - Evaluation of the evidence between consumption of refined grains and health outcomes. AB - This review evaluates the available evidence on the relationship between consumption of refined grains and health outcomes. A total of 135 relevant articles were identified from database searches of studies published between 2000 and 2010. The great majority found no associations between the intake of refined grain foods and cardiovascular disease, diabetes, weight gain, or overall mortality. A few studies found that very high intakes might be associated with some types of cancers, but at moderate levels of consumption the risks were not significant. The totality of evidence shows that consumption of up to 50% of all grain foods as refined-grain foods (without high levels of added fat, sugar, or sodium) is not associated with any increased disease risk. Nonetheless, eating more whole-grain foods remains an important health recommendation, and most consumers will need to reduce their current consumption of refined grains to no more than one-third to one-half of all grains in order to meet the targets for whole-grain foods. PMID- 22300596 TI - Role of pancreatic-derived factor in type 2 diabetes: evidence from pancreatic beta cells and liver. AB - Pancreatic-derived factor (PANDER) is a cytokine-like protein that is highly expressed in pancreatic islets. In vitro, PANDER pretreatment or viral-mediated overexpression promotes apoptosis of islet beta cells. Under conditions of insulin resistance, chronic hyperglycemia potently activates PANDER expression and stimulates the cosecretion of insulin and PANDER in beta cells. PANDER binds to the liver cell membrane and induces insulin resistance, resulting in increased gluconeogenesis. Recently, PANDER was found to be expressed in rodent and human liver, and its expression is increased in the liver of diabetic mice and rats. Hepatic overexpression of PANDER promotes lipogenesis in the liver and induces insulin resistance in C57BL/6 mice, whereas the inactivation of hepatic PANDER markedly reduces steatosis, insulin resistance, and hyperglycemia in db/db mice. PANDER deficiency protects mice from high-fat-diet-induced hyperglycemia by decreasing gluconeogenesis in the liver. In summary, PANDER plays an important role in the progression of type 2 diabetes by negatively regulating islet beta cell function and insulin sensitivity in the liver. PMID- 22300597 TI - Anticoagulant activity of select dietary supplements. AB - This review considers the potential of certain dietary supplements, including garlic, Ginkgo biloba, ginger, ginseng, fish oil, and vitamin E, to interfere with hemostasis. Dietary supplements are common components of the diet in the United States, with about half the US adult population taking some type of dietary supplement regularly. It has been suggested that some supplements could adversely affect coagulation when taken alone or in combination with antiplatelet medications. Supplements could alter hemostasis by a variety of mechanisms, such as reducing platelet aggregation or inhibiting arachidonic acid, a cellular signaling messenger and inflammatory intermediate. To conduct this review, multiple databases were searched using a variety of search terms to ensure relevant papers were located. Moderate to severe adverse events, such as spinal epidural hematoma, spontaneous intracerebral hemorrhage, retrobulbar hemorrhage, subarachnoid hemorrhage, spontaneous hyphema, and postoperative bleeding, have occasionally been anecdotally associated with consumption of dietary supplements. However, the number of controlled studies in the literature is too limited to demonstrate consistent anticoagulant effects of dietary supplements alone or in combination with drug therapy. PMID- 22300598 TI - Improving the effectiveness of nutritional information policies: assessment of unconscious pleasure mechanisms involved in food-choice decisions. AB - The rise in obesity in many countries has led to the emergence of nutritional information policies that aim to change people's diets. Changing an individual's diet is an ambitious goal, since numerous factors influence a person's food choice decisions, many of which are made unconsciously. These frequently subconscious processes should not be underestimated in food-choice behavior, as they play a major role in food diet composition. In this review, research in cognitive experimental psychology and neuroscience provides the basis for a critical analysis of the role of pleasure in eating behaviors. An assessment of the main characteristics of nutritional policies is provided, followed by recent findings showing that food choices are guided primarily by automatic emotional processes. Neuroimaging and behavioral studies, which provide new insights into the relationships between emotions and food both in lean persons and in persons with eating disorders, are reported as well. Lastly, the argument is presented that future nutritional policies can be more effective if they associate healthy food with eating pleasure. PMID- 22300600 TI - Visual mismatch negativity elicited by facial expressions: new evidence from the equiprobable paradigm. AB - BACKGROUND: Converging evidence revealed that facial expressions are processed automatically. Recently, there is evidence that facial expressions might elicit the visual mismatch negativity (MMN), expression MMN (EMMN), reflecting that facial expression could be processed under non-attentional condition. In the present study, using a cross modality task we attempted to investigate whether there is a memory-comparison-based EMMN. METHODS: 12 normal adults were instructed to simultaneously listen to a story and pay attention to a non patterned white circle as a visual target interspersed among face stimuli. In the oddball block, the sad face was the deviant with a probability of 20% and the neutral face was the standard with a probability of 80%; in the control block, the identical sad face was presented with other four kinds of face stimuli with equal probability (20% for each). Electroencephalogram (EEG) was continuously recorded and ERPs (event-related potentials) in response to each kind of face stimuli were obtained. Oddball-EMMN in the oddball block was obtained by subtracting the ERPs elicited by the neutral faces (standard) from those by the sad faces (deviant), while controlled-EMMN was obtained by subtracting the ERPs elicited by the sad faces in the control block from those by the sad faces in the oddball block. Both EMMNs were measured and analyzed by ANOVAs (Analysis of Variance) with repeated measurements. sLORETA (standardized low-resolution brain electromagnetic tomography) was used to investigate the cortical generators of controlled-EMMN. RESULTS: Both the oddball-EMMN in deviant-standard comparison and the controlled-EMMN in deviant-control comparison were observed at occipital temporal regions with right hemisphere predominance. The oddball-EMMN was bigger and earlier than the controlled-EMMN because, besides the memory-based comparison, the former included a difference of refractoriness due to the distinction of presented probability between the deviant and standard face stimuli. The source analysis of controlled-EMMN indicated a current source primarily involved in posterior areas including superior temporal gyrus, postcentral gyrus, inferior parietal lobule as well as the insula. CONCLUSIONS: The valid EMMN properly reflecting the memory-based comparison of facial expressions could be obtained, i.e., the controlled-EMMN. PMID- 22300601 TI - A new diagnostic algorithm for antibody-mediated microcirculation inflammation in kidney transplants. AB - We studied the significance of microcirculation inflammation in kidney transplants, including 329 indication biopsies from 251 renal allograft recipients, who were mostly nonpresensitized (crossmatch negative). Glomerulitis (g) and peritubular capillaritis (ptc) were often associated with antibody mediated rejection (65% and 75%, respectively), but were also found in other diseases in the absence of donor-specific antibody (DSA): T-cell-mediated rejection (ptc, g), glomerulonephritis (g) and acute tubular necrosis (ptc). To develop rules for reducing the nonspecificity of microcirculation inflammation and defining the best grading thresholds associated with DSA, we built and validated a decision tree to predict DSA. The decision tree revealed that g + ptc sum (addition of g-score plus ptc-score) was the best predictor of DSA, followed by time posttransplant, then C4d, which had a small role. Late biopsies with g + ptc > 0 showed higher frequency of DSA compared to early biopsies with g + ptc > 0 (79% vs. 27%). Microcirculation inflammation in early biopsies was often false positive (antibody-independent). The decision tree predicted DSA with higher sensitivity and accuracy than C4d staining. Microcirculation inflammation sum score predicted graft failure independently of time, C4d and transplant glomerulopathy. Thus any degree of microcirculation inflammation in late kidney transplant biopsies strongly indicates presence of DSA and predicts progression to graft failure. PMID- 22300602 TI - Treatment of Erdheim-Chester disease with long-term high-dose interferon-alpha. AB - OBJECTIVES: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, characterized by a foamy CD68+, CD1a- histiocyte tissue infiltration. Efficacy of standard doses of interferon-alpha-2a (IFNalpha) has been suggested in a small series but with variation, depending on the organs involved. Our aim was to report our single-center experience about the use of high-dose IFNalpha in ECD. METHODS: Twenty-four ECD patients have received high dose IFNalpha (IFNalpha >=18 mIU/wk or pegylated-IFNalpha >=180 MUg/wk). IFNalpha efficacy was evaluated clinically and morphologically using a standardized protocol (median follow-up 19 months). RESULTS: Indication for treatment was central nervous system and/or heart involvement (n = 20), exophthalmos (n = 1), and standard-dose IFNalpha inefficacy (n = 3). High-dose IFNalpha was effective in 16 patients (67%) with improvement (n = 11, 46%) and stabilization (n = 5, 21%). Late and gradual improvement was observed during prolonged follow-up in most patients. The efficacy of high-dose IFNalpha was dependent on the organs involved: central nervous system and heart improvement or stabilization occurred in 7/11 (64%) and 11/14 (79%) patients, respectively. Six patients (25%) worsened. High doses of IFNalpha were well-tolerated: 13 (54.2%) patients had side effects but treatment interruption was infrequent (n = 3, 12.5%). CONCLUSIONS: High-dose IFNalpha may be effective in severe ECD. Improvement may be slow, and high-dose IFNalpha treatment should be prolonged. PMID- 22300603 TI - Gait analysis of the lower limb in patients with rheumatoid arthritis: a systematic review. AB - INTRODUCTION: In rheumatoid arthritis (RA), signs and symptoms of feet and ankle are common. To evaluate the dynamic function of feet and ankles, namely walking, a variety of gait studies have been published. In this systematic review, we provide a systematic overview of the available gait studies in RA, give a clinimetrical assignment, and review the general conclusions regarding gait in RA. METHODS: A systematic literature search within the databases PubMed, CINAHL, sportdiscus, Embase, and Scopus was described and performed and delivered 78 original gait studies that were included for further data extraction. RESULTS: The clinimetrical quality of the 78 included RA gait studies measured according a tailored QUADAS item list and proposed clinimetrical criteria by Terwee and coworkers are moderate. General conclusions regarding the walking abnormalities of RA patients point to a slower walk, longer double support time, and avoidance of extreme positions. Frequently found static features in RA are hallux valgus, pes planovalgus, and hind foot abnormalities. CONCLUSIONS: Gait studies in RA patients show moderate clinimetrical properties, but are a challenging way of expressing walking disability. Future gait research should focus on more uniformity in methodology. When this need is satisfied, more clinical applicable conclusions can be drawn. PMID- 22300604 TI - [Endocrine disruptors and obesity: obesogens]. AB - Incidence and prevalence of owerweight and obesity have greatly increased over the past three decades in almost all countries around the world. This phenomenon is not easily explained by lifestyle changes in populations with very different initial habits. This has led to consider the influence of other factors, the so called endocrine disruptors, and more specifically obesogens. This study reviewed the available evidence about polluting chemical substances which may potentially be obesogens in humans: DES, genistein, bisphenol A, organotins (TBT, TPT), and phthalates. The first three groups of substances mainly act upon estrogen receptors, while organotins and phthalates activate PPARgamma. It was concluded that evidence exists of the obesogenic effect of these chemical substances in tissues and experimental animals, but few data are available in humans. PMID- 22300605 TI - The role of gut hormones in controlling the food intake: what is their role in emerging diseases? AB - Central nervous system (CNS) receives peripheral relevant information that are able to regulate individual's energy balance through metabolic, neural, and endocrine signals. Ingested nutrients come into contact with multiple sites in the gastrointestinal tract that have the potential to alter peptide and neural signaling. There is a strong relationship between CNS and those peripheral signals (as gastrointestinal hormones) in the control of food intake. The purpose of this review is to give updated information about the role of gut hormones as mediators of feeding behavior and of different nutrients in modulating gut hormones production. The role of gut hormones in the pathogenesis of emerging diseases as obesity and non-alcoholic fatty liver disease (NAFLD) is also discussed together with the possible role of these peripheral signals as targets of future therapeutic options. PMID- 22300606 TI - Mechanisms underlying CO2 diffusion in leaves. AB - Plants provide an excellent system to study CO(2) diffusion because, under light saturated conditions, photosynthesis is limited by CO(2) availability. Recent findings indicate that CO(2) diffusion in leaves can be variable in a short time range. Mesophyll CO(2) conductance could change independently from stomata movement or CO(2) fixing reactions and it was suggested that, beside others, the membranes are mesophyll CO(2) conductance limiting components. Specific aquaporins as membrane intrinsic pore proteins are considered to have a function in the modification of membrane CO(2) conductivity. Because of conflicting data, the mechanism of membrane CO(2) diffusion in plants and animals is a matter of a controversy vivid debate in the scientific community. On one hand, data from biophysics are in favor of CO(2) diffusion limiting mechanisms completely independent from membrane structure and membrane components. On the other, there is increasing evidence from physiology that a change in membrane composition has an effect on CO(2) diffusion. PMID- 22300607 TI - Urinary morbidity after permanent prostate brachytherapy - impact of dose to the urethra vs. sources placed in close vicinity to the urethra. AB - BACKGROUND AND PURPOSE: The impact of the dose to the urethra and sources placed close to the urethra on urinary morbidity after permanent prostate brachytherapy (PPB) is not well known. MATERIALS AND METHODS: Fifty-nine patients were surveyed prospectively before treatment (A), 1 month after (B) and > 1 year after PPB (C) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Computed tomography (CT) postimplant scans were performed at days 1 (Foley catheter in situ) and 30 after PPB and sources within 5mm of the urethra at day 1 were identified. RESULTS: As opposed to the urethral dose-volume histogram, a larger number of sources within 5mm of the urethra at day 1 predicted significantly larger urinary bother score changes at times B and C - with an impact on incontinence and frequency (e.g. moderate/big problem with leaking urine in 25% vs. 3%, p = 0.02; moderate/big problem with frequent urination in 33% vs. 7%, p < 0.01, at time C with vs. without >= 3 sources in a single strand placed close to the urethra). CONCLUSIONS: Placement of sources with a minimum distance of a few mm to the urethra should be a major aim to avoid urinary morbidity irrespective of the urethral dose-volume histogram. PMID- 22300608 TI - A phase I/II study of gemcitabine-concurrent proton radiotherapy for locally advanced pancreatic cancer without distant metastasis. AB - PURPOSE: We conducted the study to assess the feasibility and efficacy of gemcitabine-concurrent proton radiotherapy (GPT) for locally advanced pancreatic cancer (LAPC). MATERIALS AND METHODS: Of all 50 patients who participated in the study, 5 patients with gastrointestinal (GI)-adjacent LAPC were enrolled in P-1 (50 Gy equivalent [GyE] in 25 fractions) and 5 patients with non-GI-adjacent LAPC in P-2 (70.2 GyE in 26 fractions), and 40 patients with LAPC regardless of GI adjacency in P-3 (67.5 GyE in 25 fractions using the field-within-a-field technique). In every protocol, gemcitabine (800 mg/m(2)/week for 3 weeks) was administered concurrently. Every patient received adjuvant chemotherapy including gemcitabine after GPT within the tolerable limit. RESULTS: The median follow-up period was 12.5 months. The scheduled GPT was feasible for all except 6 patients (12%) due to acute hematologic or GI toxicities. Grade 3 or greater late gastric ulcer and hemorrhage were seen in 5 patients (10%) in P-2 and P-3. The one-year freedom from local-progression, progression-free, and overall survival rates were 81.7%, 64.3%, and 76.8%, respectively. CONCLUSION: GPT was feasible and showed high efficacy. Although the number of patients and the follow-up periods are insufficient, the clinical results seem very encouraging. PMID- 22300609 TI - Prognostic significance of the total dose of cisplatin administered during concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. AB - BACKGROUND AND PURPOSE: Concurrent chemoradiotherapy (CRT) confers survival benefit over radiotherapy (RT) alone in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). This study explored the prognostic significance of the total dose of cisplatin delivered during CRT. MATERIALS AND METHODS: A retrospective analysis was performed in patients with stage II to IVB NPC (AJCC 6th edition) who participated in 3 prospective studies. All patients received cisplatin at a fixed dose of 40 mg/m(2)/week during a 6-7-weeks course of CRT. Chi-square test was used in the univariate analysis. Relationship between prognostic factors, the total dose of cisplatin administered and time-to-event endpoints were analyzed with the Cox Hazards model. RESULTS: Two hundred and forty-one patients were identified with the following stage distribution: Stage II=13.7%, III=45.2%, IV=41.1%. The median total number of cycles of cisplatin administered per patient was 5 cycles (range 1-8 cycles). At a median follow-up of 56.5 months (range 4.2-200.2 months), 93 patients (38.6%) had relapsed and 85 patients (35.2%) died. For all patients, the total number of cycles of cisplatin delivered was significantly associated with survival in the univariate but not the multivariate analysis. In a sub-group analysis of 142 patients with stage II and III NPC, patients who received more than 5 cycles of cisplatin had significantly better overall survival than those who did not (hazard ratio 0.44; 95% confidence interval, 0.23-0.85; p=0.02). CONCLUSION: Number of cycles of cisplatin delivered is an independent prognostic factor in patients with stage II III NPC undergoing CRT with weekly cisplatin. PMID- 22300610 TI - Out-of-field contributions for IMRT and volumetric modulated arc therapy measured using gafchromic films and compared to calculations using a superposition/convolution based treatment planning system. AB - PURPOSE: To quantify the whole-body-dose delivered during the application of new techniques and compare them to the results obtained by treatment planning systems. The ultimate goal being the use of planning data in combination with complication data to assess the impact of low doses of ionizing radiation. METHODS: A film technique using gafchromic films to assess low doses was used on simplified phantoms and compared to data from treatment planning systems as well as a simplified whole body dose calculation system (Peridose). The types of treatment include open fields, intensity modulated radiation therapy (IMRT) and volumetric arc treatments. The film measurements were confirmed using TLDs in Alderson phantoms. In addition neutron contributions were measured as these are not taken into account in the current modern treatment planning systems, but can add significantly to the patient's whole body dose. RESULTS: Dose outside of the treatment plane diminished to 1% of the prescribed dose, this for open fields, IMRT and rotational treatments alike. Noteworthy was an increase at about 20cm from the central plane in IMRT, and in a more limited fashion for volumetric modulated arc treatment. In open fields this was not observed. Treatment planning systems were good at determining the out-of-field doses of single field treatments. In complex plans the TPS underestimated the dose to the patient. At distances greater than 20cm from the field edge, these systems did not predict any dose. The Peridose program performed well in the case of classical treatments. In the case of IMRT treatments, the overall evolution of the dose as a function of the distance to the field was well-modeled. However, an over estimation of the order of 60-80% was observed, leaving the possibility for a corrective factor based on a point measurement. Dose levels over the whole body were of the order 100mGy or higher over a complete treatment for the more complex treatments. Neutron dose levels were of the order single digit mSv for 10MV treatments. For 18MV the level of neutron contribution was in agreement with recent publications, corroborating reports that the dose from neutrons is lower than previously reported. PMID- 22300611 TI - Birthing outside the system: perceptions of risk amongst Australian women who have freebirths and high risk homebirths. AB - BACKGROUND: homebirth for low risk women attended by competent midwives who are networked within a responsive maternity care service is supported by research as safe. Concerns exist over the safety of homebirths which are unattended by trained health professionals, or for women with medically defined risk factors. Both these birth choices are unsupported by mainstream maternity care options in Australia and therefore represent birth choices considered to be 'outside the system'. AIM: to explore the perceptions of risk held by women who choose to have a freebirth (birth at home intentionally unattended by a trained birth attendant) or a 'high-risk' homebirth (professionally attended home birth where a mother or baby has medically defined risk factors). Both of these choices are considered to be 'outside the system'. METHODS: twenty women were interviewed about their choice to 'birth outside the system', nine choosing freebirth and 11 choosing to have an attended homebirth despite the presence of medically defined risk factors; three were primiparous and seventeen were multiparous. Women intending to have, or having had a freebirth or high risk homebirth, were interviewed using semi-structured interviews. Interviews were transcribed and analysed using thematic analysis. FINDINGS: the three main themes about perceptions of risk that were evident in this study were: 'Birth always has an element of risk', 'The hospital is not the safest place to have a baby'; and 'interference is a risk'. DISCUSSION: the participants acknowledge that birth is a time in life that carries an element of risk. They perceive that hospital represents a more risky place to give birth than at home and that interventions and interruptions during labour and birth increase risk. Women who birth outside the system perceive the risks of birth in hospital differently to most women. These women feel that by birthing outside the system they are making a choice that protects them and their babies from the risks associated with birthing in hospital and thus provides them with the best and safest birthing option. CONCLUSION: in pursuing the best for themselves and their babies, women who birth outside the system spent a lot of time and energy considering the risks and weighing these up. For them birth in hospital is considered less safe than birth at home. PMID- 22300612 TI - Targeted oxygen therapy in special care nurseries: is uniformity a good thing? AB - AIM: There is wide variation in the commencement of inspired oxygen (FiO2) and the oxygen saturation (SpO(2) ) targets set in special care nurseries (SCNs). Evidence supports minimising unnecessary oxygen exposure. Does the introduction of a protocol advocating the uniform approach of commencing FiO2 at 30% and targeting SpO2 of 94-96% for infants >= 33 weeks gestation with respiratory distress reduce oxygen exposure? METHODS: A 'Before After' study was undertaken in three SCNs. Data were recorded for all infants admitted to the SCNs who required oxygen over a 3-year period. Infants were analysed in gestational age groups: 33-36 weeks (late preterm) and +37 weeks (term/post-term). RESULTS: Of the 19,830 infants born, 868 (4%) were treated with oxygen. The introduction of an oxygen-targeting protocol resulted in a statistically and clinically significant reduction in the proportion of infants who were treated with any oxygen for 1 h or more, 4 h or more and in the proportion who received >30% FiO2 for 1 h or more (all P <= 0.01). This reduction was significant for infants of both gestational age groups. The median duration of oxygen for term/post-term infants was reduced from 12 h pre-protocol to 10 h post-protocol (P= 0.01); however, no significant difference was found for the preterm group (reduced from 11 to 8 h, P= 0.07). CONCLUSION: Introduction of a uniform oxygen protocol in SCNs for infants >= 33 weeks gestation with respiratory distress reduces the number of infants receiving oxygen and, in term infants, the duration of oxygen exposure. PMID- 22300614 TI - Long-term outcome of isolated diaphyseal radius fractures with and without dislocation of the distal radioulnar joint. AB - PURPOSE: We tested the hypothesis that there are no differences between apparently isolated fractures of the radial diaphysis and isolated fractures of the radial diaphysis with concomitant dislocation of the distal radioulnar joint (DRUJ) in function, disability, and DRUJ stability more than 13 years after near anatomic open reduction with plate and screw fixation. METHODS: We evaluated 17 adult patients with a diaphyseal fracture of the radius without a fracture of the ulna an average of 19 years after surgery (range, 13-33 y). Of these patients, 7 had concomitant dislocation of the DRUJ (Galeazzi fracture). At the long-term follow-up, we evaluated function with several composite scores, stability of the DRUJ, and arm-specific disability by using the Disabilities of Arm, Shoulder, and Hand questionnaire. RESULTS: The average scores were 96 (range, 85-100) on the Mayo Modified Wrist Score, 95 (range, 80-100) on the Mayo Elbow Performance Index, and 5 (range, 0-33) on the Disabilities of Arm, Shoulder, and Hand questionnaire. There were no significant differences between patients with and without DRUJ dislocation. No patients had greater laxity of the DRUJ than the opposite uninjured side. CONCLUSIONS: Near-anatomic open reduction and internal fixation of diaphyseal radius fractures with and without associated DRUJ dislocation have comparable long-term results. PMID- 22300613 TI - Influence of berry polyphenols on receptor signaling and cell-death pathways: implications for breast cancer prevention. AB - Breast cancer is the most commonly diagnosed cancer among women worldwide. Many women have become more aware of the benefits of increasing fruit consumption, as part of a healthy lifestyle, for the prevention of cancer. The mechanisms by which fruits, including berries, prevent breast cancer can be partially explained by exploring their interactions with pathways known to influence cell proliferation and evasion of cell-death. Two receptor pathways, estrogen receptor (ER) and tyrosine kinase receptors, especially the epidermal growth factor receptor (EGFR) family, are drivers of cell proliferation and play a significant role in the development of both primary and recurrent breast cancer. There is strong evidence to show that several phytochemicals present in berries such as cyanidin, delphinidin, quercetin, kaempferol, ellagic acid, resveratrol, and pterostilbene interact with and alter the effects of these pathways. Furthermore, they also induce cell death (apoptosis and autophagy) via their influence on kinase signaling. This review summarizes in vitro data regarding the interaction of berry polyphenols with the specific receptors and the mechanisms by which they induce cell death. This paper also presents in vivo data of primary breast cancer prevention by individual compounds and whole berries. Finally, a possible role for berries and berry compounds in the prevention of breast cancer and a perspective on the areas that require further research are presented. PMID- 22300615 TI - Thrombin stimulates stress fiber assembly in RPE cells by PKC/CPI-17-mediated MLCP inactivation. AB - Most retinal proliferative diseases involve blood-retinal barrier (BRB) breakdown, exposing the retinal pigment epithelium (RPE) to thrombin, which triggers cell transformation, proliferation and migration through the activation of PAR-1. These processes require the assembly of contractile stress fibers containing actin and non-muscle myosin II, which allow cell movement upon phosphorylation of the myosin light chains (MLCs). PKC family of kinases promotes agonist-mediated contraction in smooth muscle and endothelial cells through the activation of its downstream target, the PKC-potentiated inhibitory protein of 17 kDa (CPI-17), which specifically inhibits MLC phosphatase. Although the participation of PKC in RPE cell transdifferentiation has been suggested, the role of PKC/CPI-17 signaling has not been investigated. The purpose of this study was to analyze the involvement of specific PKC isoenzymes and their effector protein CPI-17 in thrombin-induced MLC phosphorylation and actin stress fiber assembly in RPE cells. Rat RPE cells in primary culture were shown to respond to thrombin stimulation by activation of conventional, novel and atypical PKC isoforms and the downstream phosphorylation of CPI-17 and MLC, which in turn promoted actin stress fiber assembly. These effects were prevented by the pharmacological inhibition of conventional PKC isoenzymes (Ro-32-0432) and novel PKCdelta (rottlerin and deltaV1-1 antagonist peptide), as well as by myristoylated pseudosubstrates specifically directed to conventional and atypical PKC isoforms. Thrombin effects were mimicked by phorbol 12-myristate 13-acetate (PMA), further confirming the involvement of diacylglycerol (DAG)-sensitive classical and novel PKC isoforms in thrombin-induced actin cytoskeleton modification. The present work shows, for the first time, the functional expression of the oncoprotein CPI-17 in RPE cells and suggests that PKC/CPI-17 signaling is involved in the control of actin cytoskeletal remodeling leading to cell motility in RPE cells exposed to thrombin, and hence could contribute to the development of proliferative eye diseases. PMID- 22300616 TI - Effects of cardiotonic steroids on trabecular meshwork cells: search for mediator of ouabain-enhanced outflow facility. AB - Lowering intraocular pressure (IOP) is currently the only strategy documented to slow the onset and progression of glaucomatous blindness. Ouabain, a cardiotonic glycoside inhibitor of Na(+), K(+)-activated ATPase, was recently reported to enhance outflow facility in porcine anterior segments at concentrations as low as 30 nM for >=4 h, suggesting a novel approach to lowering IOP. The underlying mechanism is unknown, but associated cytoskeletal changes were observed in porcine trabecular meshwork cells. We have previously found that changes in ATP release and subsequent ectoenzymatic conversion to adenosine may play a role in linking cytoskeletal remodeling with modulation of outflow resistance. We now tested whether altered ATP release might also be a mediator of ouabain's effect on outflow facility. ATP release from transformed human TM5 and explant-derived human trabecular meshwork cells was measured by the luciferin-luciferase reaction. Matrix metalloproteinases (MMPs) were studied by zymography, cell Na(+) concentration by SBFI fluorometry, gene expression of ATP-release pathways by real-time PCR, cell volume by electronic cell sorting and cell viability by the LDH and MTT methods. Actin was examined by confocal microscopy of phalloidin stained cells. Contrary to expectation, ouabain at concentrations >=10 nM inhibited swelling-triggered ATP release from TM5 cells after >=4 h of exposure. Inhibition was enhanced by increasing ouabain concentration and exposure time. Similar effects were produced by the reversible cardiac aglycone strophanthidin. Ouabain also inhibited swelling-activated ATP release from explant-derived native human TM cells. Ouabain (4 h, 30 nM and 100 nM) did not alter gene expression of the ATP-release pathways, and cell viability was unchanged by exposure to ouabain (30 nM-1 MUM). Preincubation with 30 nM ouabain for 4 h did not detectably change Na(+) level, the regulatory volume decrease (RVD) or the actin cytoskeleton of TM5 cells, but did inhibit hypotonicity-elicited ATP release. Moreover, even when N-methyl-d-glucosamine replaced Na(+) in the extracellular fluid, ouabain still inhibited swelling-initiated ATP release at 100 nM. In the absence of ouabain, extracellular ATP stimulated MMP secretion, which was largely blocked by inhibiting conversion of ATP to adenosine, as expected. In contrast, ouabain reduced ATP release, but did not alter secretion of MMP-2 and MMP-9 from cells pretreated for <=4 h. The results suggest that: (1) ouabain can trigger enhancement of outflow facility independent of its transport and actin restructuring effects exerted at higher concentration and longer duration; (2) ouabain exerts parallel independent effects on ATP release and outflow facility; and (3) these effects likely reflect ouabain-induced changes in the scaffolding and/or signaling functions of Na(+), K(+)-activated ATPase. PMID- 22300617 TI - Pulmonary rehabilitation for bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation. AB - Bronchiolitis obliterans syndrome (BOS) is a progressive, insidious lung disease affecting allogeneic hematopoietic stem cell transplantation recipients. Unfortunately, there is no standardized approach for treatment of BOS in post hematopoietic stem cell transplantation patients. Pulmonary rehabilitation is a standard treatment in emphysema, an irreversible obstructive lung disease secondary to tobacco abuse. The National Emphysema Treatment Trial (NETT) demonstrated improved exercise tolerance, decrease dyspnea, and increase of quality of life in patients with severe emphysema after pulmonary rehabilitation. We hypothesized that pulmonary rehabilitation may benefit patients with BOS. Patients with BOS were identified retrospectively from January 2005 to the present. Patients who enrolled in pulmonary rehabilitation were included in the study. We obtained summaries via chart review of each patient's progress after pulmonary rehabilitation enrollment from his or her respective rehabilitation centers. Six-minute walk distances, spirometry, and pulmonary symptoms were compared before and after the completion of pulmonary rehabilitation. We identified 11 patients with BOS documented from their pulmonologist's clinical notes who were enrolled into pulmonary rehabilitation. Ten of the 11 patients completed pulmonary rehabilitation. All patients had improvement in their 6 minute walk distances after the completion of pulmonary rehabilitation, with an average improvement in distance of 307 feet (P value = .005). Six of the 10 patients completed Short Form-36 (SF-36) questionnaires before and after rehabilitation. There was a significant improvement in the physical functioning score (P value = 0.029). Pulmonary rehabilitation seems to improve 6-minute walk distance, subjective symptoms of dyspnea, and exercise tolerance in patients with BOS. This may be an important adjunctive therapy for a debilitating disease with limited treatment options. PMID- 22300618 TI - Toll-like 4 receptor variant, Asp299Gly, and reduced risk of hemorrhagic cystitis after hematopoietic stem cell transplantation. AB - Hemorrhagic cystitis (HC) is a major cause of morbidity after hematopoietic stem cell transplantation. Toll-like receptor 4 (TLR4) is a pattern recognition receptor of the innate immune system and induces inflammation. Individuals with the single nucleotide polymorphisms Thr399Ile (rs4986791) or Asp299Gly (rs4986790) of TLR4 show diminished inflammatory responsiveness to endotoxins. The genotype of TLR4 was determined in 166 children who underwent allogeneic hematopoietic stem cell transplantation and in their donors. Asp299Gly was present in 21 patients (13%) and 24 donors (14%). Thr399Ile was found in 22 patients (13%) and 25 donors (15%). The incidence of HC was significantly lower in patients with Asp299Gly (0% vs 23%; P = .009) and in patients who underwent transplantation from a donor with Asp299Gly (4% vs 23%; P = .05). The trend was the same for Thr399Ile-donor positive (8% vs 22%; P = .17), recipient positive (9% vs 22%; P = .25), donor or recipient positive (8% vs 23%; P = .04). Multivariate analysis revealed age, conditioning with busulfan, and absence of Asp299Gly as independent risk factors for HC. In conclusion, the TLR4 Asp299Gly variant seems to confer protection against hemorrhagic cystitis. This study provides the first indication that the innate immune system through TLR4 signaling pathway plays a role in the pathogenesis of HC after hematopoietic stem cell transplantation. PMID- 22300619 TI - Transgene expression and local tissue distribution of naked and polymer-condensed plasmid DNA after intradermal administration in mice. AB - DNA vaccination using cationic polymers as carriers has the potential to be a very powerful method of immunotherapy, but typical immune responses generated have been less than robust. To better understand the details of DNA vaccine delivery in vivo, we prepared polymer/DNA complexes using three structurally distinct cationic polymers and fluorescently labeled plasmid DNA and injected them intradermally into mice. We analyzed transgene expression (luciferase) and the local tissue distribution of the labeled plasmid at the injection site at various time points (from hours to days). Comparable numbers of luciferase expressing cells were observed in the skin of mice receiving naked plasmid or polyplexes one day after transfection. At day 4, however, the polyplexes appeared to result in more transfected skin cells than naked plasmid. Live animal imaging revealed that naked plasmid dispersed quickly in the skin of mice after injection and had a wider distribution than any of the three types of polyplexes. However, naked plasmid level dropped to below detection limit after 24h, whereas polyplexes persisted for up to 2 weeks. The PEGylated polyplexes had a significantly wider distribution in the tissue than the nonPEGylated polyplexes. PEGylated polyplexes also distributed more broadly among dermal fibroblasts and allowed greater interaction with antigen-presenting cells (APCs) (dendritic cells and macrophages) starting at around 24h post-injection. By day 4, co-localization of polyplexes with APCs was observed at the injection site regardless of polymer structure, whereas small amounts of polyplexes were found in the draining lymph nodes. These in vivo findings demonstrate the superior stability of PEGylated polyplexes in physiological milieu and provide important insight on how cationic polymers could be optimized for DNA vaccine delivery. PMID- 22300620 TI - Nasal drug delivery - recent developments and future prospects. AB - The present review sets out to discuss recent developments and prospects of absorption promoters and absorption modulator systems being developed commercially by companies specialising in nasal drug delivery of normal small molecular weight drugs and biological drugs such as peptide and proteins. The absorption promoter systems selected for discussion in this review are those with the most promising preclinical and/or clinical data and sufficient toxicology data and/or company development efforts to warrant use in marketed products i.e. CPE-215 (cyclopenta decalactone (azone)) developed by CPEX Pharma, Intravail (alkylsaccharides) developed by Aegis Therapeutics, ChiSys(TM) (chitosan) and PecSys(TM) (low methylated pectin) in development by Archimedes Pharma and CriticalSorb(TM) (polyglycol mono- and diesters of 12-hydroxystearate (70%), polyethylene glycol (30%)) developed by Critical Pharmaceuticals. PMID- 22300621 TI - Evaluation of selective tumor detection by clinical magnetic resonance imaging using antibody-conjugated superparamagnetic iron oxide. AB - Active targeting by monoclonal antibodies (mAbs) combined with nanosize superparamagnetic iron oxide (SPIO) is a promising technology for magnetic resonance imaging (MRI) diagnosis. However, the clinical applicability of this technology has not been investigated using appropriate controls. It is important to evaluate the targeting technology using widely used clinical 1.5-Tesla MRI in addition to the high-Tesla experimental MRI. In this study, we measured mAb conjugated dextran-coated SPIO nanoparticles (CMDM) in vivo using clinical 1.5 Tesla MRI. MRI of tumor-bearing mice was performed using a simple comparison between positive and negative tumors derived from the same genetic background in each mouse. The system provided significant tumor-targeting specificity of the target tumor. To the best of our knowledge, this is the first report on the specific detection of target tumors by mAb-conjugated SPIO using clinical 1.5 Tesla MRI. Our observations provide clues for reliable active targeting using mAb conjugated SPIO in clinical applications. PMID- 22300622 TI - Polyelectrolyte multilayer nanoshells with hydrophobic nanodomains for delivery of Paclitaxel. AB - Efficient and effective delivery of poorly water-soluble drug molecules, which constitute a large part of commercially available drugs, is a major challenge in the field of drug delivery. Several drugs including paclitaxel (PTX) which are used for cancer treatment are hydrophobic, exhibit poor aqueous solubility and need to be delivered using an appropriate carrier. In the present work, we engineered PTX-loaded polyelectrolyte films and microcapsules by pre-complexing PTX with chemically modified derivative of hyaluronic acid (alkylamino hydrazide) containing hydrophobic nanocavities, and subsequent assembly with either poly(l lysine) (PLL) or quaternized chitosan (QCHI) as polycations. The PTX loading capacity of the films was found to be dependent on number of layers in the films as well as on the initial concentration of PTX pre-complexed to hydrophobic HA, with a loading capacity up to 5000-fold the initial PTX concentration. The films were stable in physiological medium and were degraded in the presence of hyaluronidase. The PTX-loaded microcapsules were found to decrease the viability and proliferation of MDA MB 231 breast cancer cells, while unloaded microcapsules did not impact cell viability. All together, our results highlight the potential of hyaluronan-based assemblies containing hydrophobic nanodomains for hydrophobic drug delivery. PMID- 22300623 TI - The pathogenesis of tumor-related epilepsy and its implications for clinical treatment. AB - Approximately 30-50% of patients with brain tumors present with seizures as the initial symptom. Seizures play a very important role in the quality of life, particularly in patients with slow-growing primary brain tumors. Tumor-related seizures are often refractory to antiepileptic treatment. Despite the importance of this subject to the fields of neurology, neurosurgery and neurooncology, the pathogenesis of tumor-related epilepsy remains poorly understood. This review summarizes possible mechanisms underlying the pathogenesis of tumor-related epilepsy, including both tumoral and peri-tumoral aspects. Tumor cells themselves may create intrinsic epileptogenicity, and inadequate homeostasis in the peri tumoral tissues may lead to seizure susceptibility. Other local changes in electrolytes, perfusion, metabolism, and enzymes could also contribute. It is generally accepted that changes in amino acid neurotransmission are the most important mechanism underlying tumor-related seizures, and changes in extracellular ions also play an important role. Hypoxia, acidosis, and metabolic, immunological, and inflammatory changes may also be involved in the occurrence of seizures. Knowledge of these mechanisms may provide guidance in the search for new strategies for the surgical and medical treatment of tumor-related epilepsy. PMID- 22300624 TI - 8p deletion and 9p duplication in two children with electrical status epilepticus in sleep syndrome. AB - We describe two individuals with the same chromosomal aberrations derived from an unbalanced translocation between chromosomes 8p and 9p, who presented with intellectual disabilities, dysmorphic features, and localization-related epilepsy. Several years after the onset of epilepsy, aggravation of widespread epileptic discharges during sleep resulted in the emergence of absence and/or atonic seizures in both patients; one patient additionally presented with psychomotor deterioration. These symptoms completely disappeared after treatment with ethosuximide and benzodiazepines, and marked improvement was observed in electroencephalographic findings. We review the clinical features of der(8)t(8;9) with particular focus on epileptic complications. We conclude that particular types of chromosomal aberrations may have a propensity to develop the condition categorized as electrical status epilepticus in sleep. PMID- 22300626 TI - New minimally invasive technique of perpulmonary device closure of patent ductus arteriosus through a parasternal approach. AB - BACKGROUND: Transcatheter closure and previous surgical techniques of patent ductus arteriosus (PDA) have different drawbacks. We describe a new minimally invasive technique of perpulmonary device closure of a PDA and evaluate the feasibility, safety, and advantages of this technique. METHODS: Seventy-nine patients aged 0.4 to 52 years (mean, 18+/-15 years) underwent perpulmonary device closure of PDA. A 2- to 3-cm parasternal incision was made in the left second intercostal space. The pericardium was incised. A specially designed delivery sheath loaded with the device was inserted through the pursestring sutures into the pulmonary trunk. Under transesophageal echocardiographic guidance, it was advanced through the PDA into the descending aorta, and the device was subsequently deployed. In patients with a large PDA or significant pulmonary hypertension, a device stay suture was passed through the device and tied down with the pursestring sutures after device release to avoid device dislocation. RESULTS: The procedure was successful in 78 patients (99%). The device stay suture was used in 21 patients. The mean minimum PDA diameter was 6.0+/-3.4 mm (range, 1.7 to 18.0 mm). The implanted device size was 9.6+/-4.1 mm (range, 4 to 24 mm). The mean intrapulmonary manipulation time was 15+/-13 minutes (range, 2 to 55 minutes). During the follow-up period of 3 to 24 months, a minor residual shunt was found in 2 patients. CONCLUSIONS: Perpulmonary device closure of a PDA is simple, safe, and efficacious. It has the advantages of more accurate device positioning and reduces the risk of device embolization by using the device stay suture. PMID- 22300625 TI - 2012 ACCF/AATS/SCAI/STS expert consensus document on transcatheter aortic valve replacement: developed in collaboration with the American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Failure Society of America, Mended Hearts, Society of Cardiovascular Anesthesiologists, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance. PMID- 22300627 TI - Assessment of the relationship between Contegra conduit size and early valvar insufficiency. AB - BACKGROUND: Contegra bovine jugular vein (BJV) conduit results vary widely, and little attention has been directed at assessment of early conduit insufficiency. Conduit insufficiency is graded subjectively, and criteria vary. Several studies have used branch pulmonary artery flow reversal (BPAFR) to define severe conduit insufficiency. BJV valves are larger than human pulmonary valves of similar diameter. We hypothesize that anatomic differences between BJV and human pulmonary valves limit the use of BPAFR in the evaluation of BJV competence. Our purposes were to (1) assess the prevalence of early and 6-month BJV conduit insufficiency in our patients, (2) determine if conduit size affects BJV competence, and (3) determine if BPAFR is a specific discriminator of severe conduit insufficiency. METHODS: We reviewed 135 BJV conduits. One cardiologist blinded to original reports reviewed postoperative and 6-month echocardiograms. Conduits were grouped by size: group 1, 12 to 14 mm (n=51), and group 2, 16 to 22 mm (n=84). Moderate or greater insufficiency was considered clinically significant. RESULTS: Early conduit insufficiency was common in group 1 (37%) and rare in group 2 (5%, p<0.0001). After excluding conduits with significant insufficiency, BPAFR occurred in 18% (group 1, 27%; group 2, 13%; p=0.02). At follow-up, insufficiency worsened in group 1 but was stable in group 2. CONCLUSIONS: Early conduit insufficiency is common and worsens with follow-up in small BJVs. Conduit insufficiency is limited in larger sizes and remains stable. BJV exhibits BPAFR commonly in the absence of significant conduit insufficiency. BPAFR should not be used as a primary criterion for grading insufficiency in BJV conduits. PMID- 22300628 TI - Colorful molecular diagnostics. PMID- 22300629 TI - Refining noninvasive prenatal diagnosis with single-molecule next-generation sequencing. PMID- 22300630 TI - Comparative genomic analysis of two brucellaphages of distant origins. AB - Here, we present the first complete genome sequence of brucellaphage Tbilisi (Tb) and compared it with that of Pr, a broad host-range brucellaphage recently isolated in Mexico. The genomes consist of 41,148 bp (Tb) and 38,253 bp (Pr), they differ mainly in the region encoding structural proteins, in which the genome of Tb shows two major insertions. Both genomes share 99.87% nucleotide identity, a high percentage of identity among phages isolated at so globally distant locations and temporally different occasions. Sequence analysis revealed 57 conserved ORFs, three transcriptional terminators and four putative transcriptional promoters. The co-occurrence of an ORF encoding a putative DnaA like protein and a putative oriC-like origin of replication was found in both brucellaphages genomes, a feature not described in any other phage genome. These elements suggest that DNA replication in brucellaphages differs from other phages, and might resemble that of bacterial chromosomes. PMID- 22300631 TI - Age-associated DNA methylation in pediatric populations. AB - DNA methylation (DNAm) plays diverse roles in human biology, but this dynamic epigenetic mark remains far from fully characterized. Although earlier studies uncovered loci that undergo age-associated DNAm changes in adults, little is known about such changes during childhood. Despite profound DNAm plasticity during embryogenesis, monozygotic twins show indistinguishable childhood methylation, suggesting that DNAm is highly coordinated throughout early development. Here we examine the methylation of 27,578 CpG dinucleotides in peripheral blood DNA from a cross-sectional study of 398 boys, aged 3-17 yr, and find significant age-associated changes in DNAm at 2078 loci. These findings correspond well with pyrosequencing data and replicate in a second pediatric population (N = 78). Moreover, we report a deficit of age-related loci on the X chromosome, a preference for specific nucleotides immediately surrounding the interrogated CpG dinucleotide, and a primary association with developmental and immune ontological functions. Meta-analysis (N = 1158) with two adult populations reveals that despite a significant overlap of age-associated loci, most methylation changes do not follow a lifelong linear pattern due to a threefold to fourfold higher rate of change in children compared with adults; consequently, the vast majority of changes are more accurately modeled as a function of logarithmic age. We therefore conclude that age-related DNAm changes in peripheral blood occur more rapidly during childhood and are imperfectly accounted for by statistical corrections that are linear in age, further suggesting that future DNAm studies should be matched closely for age. PMID- 22300632 TI - A vast collection of microbial genes that are toxic to bacteria. AB - In the process of clone-based genome sequencing, initial assemblies frequently contain cloning gaps that can be resolved using cloning-independent methods, but the reason for their occurrence is largely unknown. By analyzing 9,328,693 sequencing clones from 393 microbial genomes, we systematically mapped more than 15,000 genes residing in cloning gaps and experimentally showed that their expression products are toxic to the Escherichia coli host. A subset of these toxic sequences was further evaluated through a series of functional assays exploring the mechanisms of their toxicity. Among these genes, our assays revealed novel toxins and restriction enzymes, and new classes of small, non coding toxic RNAs that reproducibly inhibit E. coli growth. Further analyses also revealed abundant, short, toxic DNA fragments that were predicted to suppress E. coli growth by interacting with the replication initiator DnaA. Our results show that cloning gaps, once considered the result of technical problems, actually serve as a rich source for the discovery of biotechnologically valuable functions, and suggest new modes of antimicrobial interventions. PMID- 22300633 TI - The diversity of cyanobacterial metabolism: genome analysis of multiple phototrophic microorganisms. AB - BACKGROUND: Cyanobacteria are among the most abundant organisms on Earth and represent one of the oldest and most widespread clades known in modern phylogenetics. As the only known prokaryotes capable of oxygenic photosynthesis, cyanobacteria are considered to be a promising resource for renewable fuels and natural products. Our efforts to harness the sun's energy using cyanobacteria would greatly benefit from an increased understanding of the genomic diversity across multiple cyanobacterial strains. In this respect, the advent of novel sequencing techniques and the availability of several cyanobacterial genomes offers new opportunities for understanding microbial diversity and metabolic organization and evolution in diverse environments. RESULTS: Here, we report a whole genome comparison of multiple phototrophic cyanobacteria. We describe genetic diversity found within cyanobacterial genomes, specifically with respect to metabolic functionality. Our results are based on pair-wise comparison of protein sequences and concomitant construction of clusters of likely ortholog genes. We differentiate between core, shared and unique genes and show that the majority of genes are associated with a single genome. In contrast, genes with metabolic function are strongly overrepresented within the core genome that is common to all considered strains. The analysis of metabolic diversity within core carbon metabolism reveals parts of the metabolic networks that are highly conserved, as well as highly fragmented pathways. CONCLUSIONS: Our results have direct implications for resource allocation and further sequencing projects. It can be extrapolated that the number of newly identified genes still significantly increases with increasing number of new sequenced genomes. Furthermore, genome analysis of multiple phototrophic strains allows us to obtain a detailed picture of metabolic diversity that can serve as a starting point for biotechnological applications and automated metabolic reconstructions. PMID- 22300634 TI - Intrauterine growth and neuropsychological performance in very low birth weight preschoolers. AB - In this study we examined the association between intrauterine growth, indexed either as a categorical variable or continuous dimension, and neuropsychological outcome, in a very low birth weight (VLBW) sample of 143 preschoolers. When the commonly used split at the 10th percentile rank was applied to classify intrauterine growth restriction (IUGR), we found that the growth restricted group (n = 25) exhibited significantly poorer performance in the global motor domain, but not on any other neuropsychological measure. In contrast, when adequacy of intrauterine growth was indexed by standardized birth weight, a continuous dimension, this early risk factor explained a unique portion of the variance in global cognitive abilities and visuospatial skills, as well as in global, fine, and gross motor skills. These findings are consistent with recent magnetic resonance imaging data disclosing global neurodevelopmental changes in the brains of preterm infants with IUGR. When cases classified with IUGR (<10th percentile) were excluded, the relationship between adequacy of intrauterine growth and global cognitive abilities remained significant despite range restriction. Hence, an association between appropriateness of intrauterine growth and global intellectual outcome may be observed even within the population of VLBW preschoolers with adequate standardized birth weight. PMID- 22300635 TI - The conclusiveness of less-invasive imaging techniques (computer tomography, X ray) with regard to their identification of bone diseases in a primate model (Callithrix jacchus). AB - BACKGROUND: Although common marmosets seem to be appropriate animal models to examine bone diseases, no data about the conclusiveness of less-invasive techniques are available. Therefore, the aim was to combine different techniques to analyse changes in bone metabolism of common marmosets with bone diseases. METHODS: Five monkeys were examined by X-ray, computer tomography (CT), histology and immunohistochemistry (IHC). RESULTS: Monkeys with lowest bone mineral density (BMD) showed increased bone marrow, decreased cancellous bone and decreased contrast in X-ray. Highest alkaline phosphatase (AP)-levels were detected in bones with low elastic modulus. Expression of osteopontin (OPN), osteocalcin (OC) and runt-related transcriptions factor 2 (RUNX 2) was detected in bones with high modulus. No expression was present in bones with lower modulus. Collagen type I and V were found in every bone. CONCLUSIONS: In conclusion, CT, X-ray and AP are useful techniques to detect bone diseases in common marmosets. These observations could be confirmed by IHC. PMID- 22300636 TI - Effect of supplementary carbon addition in the treatment of low C/N high technology industrial wastewater by MBR. AB - The effect of supplementary carbon addition for the treatment of high-technology industrial wastewater in a membrane bioreactor (MBR) was investigated. The MBR was operated for 302 days under different C/N (BOD(L)/NH(4)(+)-N) ratios, i.e. 0.9-1 to 20 days, 1.6-21 to 42 days, 2.9-43 to 82 days, 3.6-83 to 141 days, 4.8 165 to 233 days and 9.3-240 to 302 days. Irrespective of the C/N ratios investigated, SS and BOD(5) removal efficiencies were above 95% and above 80% COD removal efficiency was observed. In addition, complete nitrification was observed throughout the investigation. However, denitrification and total nitrogen removal efficiencies reached their maximum values at the highest C/N ratio (9.3) investigated. Real-time PCR analysis revealed 10 times higher ammonia oxidizing bacteria to total bacteria ratio under the highest C/N ratio condition (9.3) compared to the low C/N ratio condition (1.6). PMID- 22300637 TI - Effect of quantity and composition of waste on the prediction of annual methane potential from landfills. AB - A study was conducted to investigate the effect of waste composition change on the methane production in landfills. An empirical equation for the methane potential of the mixed waste is derived based on the methane potential values of individual waste components and the compositional ratio of waste components. A correction factor was introduced in the equation and was determined from the BMP and lysimeter tests. The equation and LandGEM were applied for a full size landfill and the annual methane potential was estimated. Results showed that the changes in quantity of waste affected the annual methane potential from the landfill more than the changes of waste composition. PMID- 22300638 TI - Bed mixing and leachate recycling strategies to overcome pressure drop buildup in the biofiltration of hydrogen sulfide. AB - The effects of leachate recycling and bed mixing on the removal rate of H(2)S from waste gas stream were investigated. The experimental setup consisted of an epoxy-coated three-section biofilter with an ID of 8 cm and effective bed height of 120 cm. Bed material consisted of municipal solid waste compost and PVC bits with an overall porosity of 54% and dry bulk density of 0.456 g cm(-3). Leachate recycling had a positive effect of increasing elimination capacity (EC) up to 21 g S m(-3) bed h(-1) at recycling rates of 75 ml d(-1), but in the bed mixing period EC declined to 8 g S m(-3) bed h(-1). Pressure drop had a range of zero to 18 mm H(2)O m(-1) in the course of leachate recycling. Accumulation of sulfur reduced removal efficiency and increased pressure drop up to 110 mm H(2)O m(-1) filter during the bed mixing stage. PMID- 22300639 TI - Effects of a short text message reminder system on emergency department length of stay. AB - PURPOSE: Specialty consultations and waiting for admission to a hospital bed are major contributors to increased length of stay and overcrowding in the emergency department. We implemented a computerized short messaging service to inform care providers of patient delay in order to reduce length of stay. The purpose of this study was to evaluate the effects of this strategy on length of stay in the emergency department. METHODS: This was a before-and-after observational study. Prior to this study, we registered the mobile phone numbers of all board certified specialists into a computerized physician order entry database and developed an auto-sending short messaging program linked to consultation orders. The short message was transmitted at 2 and 4h after consultation, when a disposition was not yet established, and at 8h after the admission order if the patient was still waiting. The length of stay of consulted patients and intervals such as consultation time (registration-consultation), disposition time (consultation-admission decision), and boarding time (admission decision hospitalization) of admitted patients were compared between the pre implementation (September 2009) and post-implementation period (November 2009). Subgroup analyses of disposition time were performed according to time of consultation and the number of consultations. RESULTS: A total of 7518 patients visited the emergency department during the pre-periods and post-periods. Among them, 3335 patients required specialty consultations. The median length of stay of consulted patients decreased significantly after implementation of the messaging system (pre-207 min vs. post-193 min, p<0.001). Among admitted patients, the median length of stay decreased by 36 min from 294 min to 258 min (p<0.001). In the subgroup analysis, times for establishing patient dispositions decreased significantly when the consultation was performed at night and when there was only one department consulted. The numbers of patients with disposition times within 2 and 4h and boarding times within 8h were all increased after implementation of the short message service program. CONCLUSIONS: This study suggested that the computerized physician order entry-based short messaging service program, used to inform decision-makers of patient delay, could reduce the length of stay for consulted patients in the emergency department. PMID- 22300640 TI - A risk-prediction model for in-hospital mortality after heart transplantation in US children. AB - We sought to develop and validate a quantitative risk-prediction model for predicting the risk of posttransplant in-hospital mortality in pediatric heart transplantation (HT). Children <18 years of age who underwent primary HT in the United States during 1999-2008 (n = 2707) were identified using Organ Procurement and Transplant Network data. A risk-prediction model was developed using two thirds of the cohort (random sample), internally validated in the remaining one third, and independently validated in a cohort of 338 children transplanted during 2009-2010. The best predictive model had four categorical variables: hemodynamic support (ECMO, ventilator support, VAD support vs. medical therapy), cardiac diagnosis (repaired congenital heart disease [CHD], unrepaired CHD vs. cardiomyopathy), renal dysfunction (severe, mild-moderate vs. normal) and total bilirubin (>= 2.0, 0.6 to <2.0 vs. <0.6 mg/dL). The C-statistic (0.78) and the Hosmer-Lemeshow goodness-of-fit (p = 0.89) in the model-development cohort were replicated in the internal validation and independent validation cohorts (C statistic 0.75, 0.81 and the Hosmer-Lemeshow goodness-of-fit p = 0.49, 0.53, respectively) suggesting acceptable prediction for posttransplant in-hospital mortality. We conclude that this risk-prediction model using four factors at the time of transplant has good prediction characteristics for posttransplant in hospital mortality in children and may be useful to guide decision-making around patient listing for transplant and timing of mechanical support. PMID- 22300641 TI - Regulatory T cells exhibit decreased proliferation but enhanced suppression after pulsing with sirolimus. AB - Although regulatory T cells (Tregs) suppress allo-immunity, difficulties in their large-scale production and in maintaining their suppressive function after expansion have thus far limited their clinical applicability. Here we have used our nonhuman primate model to demonstrate that significant ex vivo Treg expansion with potent suppressive capacity can be achieved and that Treg suppressive capacity can be further enhanced by their exposure to a short pulse of sirolimus. Both unpulsed and sirolimus-pulsed Tregs (SPTs) are capable of inhibiting proliferation of multiple T cell subpopulations, including CD4(+) and CD8(+) T cells, as well as antigen-experienced CD28(+) CD95(+) memory and CD28(-) CD95(+) effector subpopulations. We further show that Tregs can be combined in vitro with CTLA4-Ig (belatacept) to lead to enhanced inhibition of allo-proliferation. SPTs undergo less proliferation in a mixed lymphocyte reaction (MLR) when compared with unpulsed Tregs, suggesting that Treg-mediated suppression may be inversely related to their proliferative capacity. SPTs also display increased expression of CD25 and CTLA4, implicating signaling through these molecules in their enhanced function. Our results suggest that the creation of SPTs may provide a novel avenue to enhance Treg-based suppression of allo-immunity, in a manner amenable to large-scale ex vivo expansion and combinatorial therapy with novel, costimulation blockade-based immunosuppression strategies. PMID- 22300642 TI - Kaiso uses all three zinc fingers and adjacent sequence motifs for high affinity binding to sequence-specific and methyl-CpG DNA targets. AB - Kaiso is a Cys(2)His(2) zinc finger (ZF) protein that mediates methyl-CpG dependent and sequence-specific transcriptional repression. As a first step towards elucidating the structural and molecular basis for recognition of these disparate DNA sequences, the minimal binding region of Kaiso was identified and optimal DNA sequences for high-affinity interactions were characterized. Contrary to previous findings, Kaiso requires all three zinc fingers plus adjacent protein regions for DNA recognition. An N-terminal extension contributes to structural stability, while an extended C-terminal region augments DNA binding. Complexes formed between the optimized Kaiso construct and both DNA sequences are suitable for future structural evaluation. PMID- 22300643 TI - A change in the sensitivity of elongation factor G to oxidation protects photosystem II from photoinhibition in Synechocystis sp. PCC 6803. AB - The repair of photosystem II (PSII) after photodamage is particularly sensitive to oxidative stress and inhibition of such repair is associated with the oxidation of specific cysteine residues in elongation factor G (EF-G), a key translation factor, in the cyanobacterium Synechocystis sp. PCC 6803. Expression of mutated EF-G with a target cysteine residue replaced by serine in Synechocystis resulted in the protection of PSII from photoinhibition. This protection was attributable to the enhanced repair of PSII via acceleration of the synthesis of the D1 protein, which might have been due to reduced sensitivity of protein synthesis to oxidative stress. PMID- 22300644 TI - The interdependence of subtype and severity: contributions of clinical and neuropsychological features to melancholia and non-melancholia in an outpatient sample. AB - Major depressive disorder is often considered to be a homogenous disorder that changes in terms of severity; however, the presence of distinct subtypes and a variety of presenting symptoms suggests much heterogeneity. Aiming to better understand the relationship between heterogeneity and diagnosis we used an exploratory approach to identify subtypes of depression on the basis of clinical symptoms and neuropsychological performance. Cluster analysis identified two groups of patients distinguished by level of cognitive dysfunction with the more severe cluster being associated with melancholic depression. While the relationship between cluster and subtype was significant, only 58% of melancholic patients were assigned to cluster 1 (the more severe cluster) and 66% of non melancholic patients assigned to cluster 2. Subtypes also displayed a distinctive profile of impairment such that melancholic patients (n = 65) displayed more variability in attention while non-melancholic patients (n = 59) displayed memory recall impairment. While melancholia and non-melancholia are associated with a more severe and less severe form of depression respectively, findings indicate that differences between melancholia and non-melancholia are more than simple variation on severity. In summary, findings provide support for the heterogeneity of depression. PMID- 22300645 TI - Nitric oxide in adaptation to altitude. AB - This review summarizes published information on the levels of nitric oxide gas (NO) in the lungs and NO-derived liquid-phase molecules in the acclimatization of visitors newly arrived at altitudes of 2500 m or more and adaptation of populations whose ancestors arrived thousands of years ago. Studies of acutely exposed visitors to high altitude focus on the first 24-48 h with just a few extending to days or weeks. Among healthy visitors, NO levels in the lung, plasma, and/or red blood cells fell within 2h, but then returned toward baseline or slightly higher by 48 h and increased above baseline by 5 days. Among visitors ill with high-altitude pulmonary edema at the time of the study or in the past, NO levels were lower than those of their healthy counterparts. As for highland populations, Tibetans had NO levels in the lung, plasma, and red blood cells that were at least double and in some cases orders of magnitude greater than other populations regardless of altitude. Red blood cell-associated nitrogen oxides were more than 200 times higher. Other highland populations had generally higher levels although not to the degree shown by Tibetans. Overall, responses of those acclimatized and those presumed to be adapted are in the same direction, although the Tibetans have much larger responses. Missing are long-term data on lowlanders at altitude showing how similar they become to the Tibetan phenotype. Also missing are data on Tibetans at low altitude to see the extent to which their phenotype is a response to the immediate environment or expressed constitutively. The mechanisms causing the visitors' and the Tibetans' high levels of NO and NO derived molecules at altitude remain unknown. Limited data suggest processes including hypoxic upregulation of NO synthase gene expression, hemoglobin-NO reactions, and genetic variation. Gains in understanding will require integrating appropriate methods and measurement techniques with indicators of adaptive function under hypoxic stress. PMID- 22300646 TI - Systemic oxidative stress is implicated in the pathogenesis of brain edema in rats with chronic liver failure. AB - Chronic liver failure leads to hyperammonemia, a central component in the pathogenesis of hepatic encephalopathy (HE); however, a correlation between blood ammonia levels and HE severity remains controversial. It is believed oxidative stress plays a role in modulating the effects of hyperammonemia. This study aimed to determine the relationship between chronic hyperammonemia, oxidative stress, and brain edema (BE) in two rat models of HE: portacaval anastomosis (PCA) and bile-duct ligation (BDL). Ammonia and reactive oxygen species (ROS) levels, BE, oxidant and antioxidant enzyme activities, as well as lipid peroxidation were assessed both systemically and centrally in these two different animal models. Then, the effects of allopurinol (xanthine oxidase inhibitor, 100mg/kg for 10days) on ROS and BE and the temporal resolution of ammonia, ROS, and BE were evaluated only in BDL rats. Similar arterial and cerebrospinal fluid ammonia levels were found in PCA and BDL rats, both significantly higher compared to their respective sham-operated controls (p<0.05). BE was detected in BDL rats (p < 0.05) but not in PCA rats. Evidence of oxidative stress was found systemically but not centrally in BDL rats: increased levels of ROS, increased activity of xanthine oxidase (oxidant enzyme), enhanced oxidative modifications on lipids, as well as decreased antioxidant defense. In PCA rats, a preserved oxidant/antioxidant balance was demonstrated. Treatment with allopurinol in BDL rats attenuated both ROS and BE, suggesting systemic oxidative stress is implicated in the pathogenesis of BE. Analysis of ROS and ammonia temporal resolution in the plasma of BDL rats suggests systemic oxidative stress might be an important "first hit", which, followed by increases in ammonia, leads to BE in chronic liver failure. In conclusion, chronic hyperammonemia and oxidative stress in combination lead to the onset of BE in rats with chronic liver failure. PMID- 22300647 TI - Quantifying the effects of body mass index on safety: reliability of a video coding procedure and utility of a rhythmic walking task. AB - OBJECTIVES: To evaluate the association between body mass index (BMI) and motor actions related to safety risks (primary aim), and to examine the reliability of a video coding procedure and the utility of a rhythmic walking task in identifying safety risks (secondary aims). DESIGN: Using a cross-sectional design, participants were filmed during a rhythmic walking task at slow, normal, and fast audio metronome paces. A video coding procedure was used to quantify signs of safety risks from the videotaped sessions. SETTING: Motor development laboratory in a university. PARTICIPANTS: Adults (N=32) with normal (n=15) and overweight (n=17) BMI scores participated. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Chi-squared analyses were conducted to compare the occurrence of coded motor actions (forward and lateral tripping) between participants with normal and overweight BMI scores. A kappa coefficient was computed as a measure of interrater reliability on the video codes. RESULTS: Participants who were overweight exhibited more safety risks compared with participants with normal BMI scores at the slow (chi(2)(1,N=32)=3.94, P<.05, d=.75) and fast (chi(2)(1,N=32)=3.85, P<.05, d=.74) metronome paces. Interrater reliability was high (kappa=.90, P<.01). CONCLUSIONS: In support of the primary aim, the findings show a relationship between overweight BMI scores and safety risks. Toward the secondary aims, the results demonstrate that a video coding procedure can be reliably used to assess safety risks and that creating tasks appropriate for assessing safety risks in overweight adults is needed. PMID- 22300648 TI - Post-genomic analyses of fungal lignocellulosic biomass degradation reveal the unexpected potential of the plant pathogen Ustilago maydis. AB - BACKGROUND: Filamentous fungi are potent biomass degraders due to their ability to thrive in ligno(hemi)cellulose-rich environments. During the last decade, fungal genome sequencing initiatives have yielded abundant information on the genes that are putatively involved in lignocellulose degradation. At present, additional experimental studies are essential to provide insights into the fungal secreted enzymatic pools involved in lignocellulose degradation. RESULTS: In this study, we performed a wide analysis of 20 filamentous fungi for which genomic data are available to investigate their biomass-hydrolysis potential. A comparison of fungal genomes and secretomes using enzyme activity profiling revealed discrepancies in carbohydrate active enzymes (CAZymes) sets dedicated to plant cell wall. Investigation of the contribution made by each secretome to the saccharification of wheat straw demonstrated that most of them individually supplemented the industrial Trichoderma reesei CL847 enzymatic cocktail. Unexpectedly, the most striking effect was obtained with the phytopathogen Ustilago maydis that improved the release of total sugars by 57% and of glucose by 22%. Proteomic analyses of the best-performing secretomes indicated a specific enzymatic mechanism of U. maydis that is likely to involve oxido-reductases and hemicellulases. CONCLUSION: This study provides insight into the lignocellulose degradation mechanisms by filamentous fungi and allows for the identification of a number of enzymes that are potentially useful to further improve the industrial lignocellulose bioconversion process. PMID- 22300649 TI - Addition of plasma exchange to glucocorticosteroids for the treatment of severe Henoch-Schonlein purpura in adults: a case series. AB - BACKGROUND: Adult Henoch-Schonlein purpura (HSP) has been associated with poor outcome and end-stage renal disease in >20% of cases. Although the benefit of adding another immunosuppressant to steroids in severe adult HSP has not been shown, the benefit of plasma exchange (PE) therapy has been poorly evaluated. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 11 consecutive patients with severe and newly diagnosed HSP since 1988 who were treated with steroids and PE. OUTCOME & MEASUREMENT: Patients' characteristics and outcome were analyzed. Birmingham Vasculitis Activity Score (BVAS), estimated glomerular filtration rate (eGFR), and proteinuria were measured at baseline, at the end of PE treatment, at months 6 and 12, and at the last visit. Side effects of corticoid treatment and PE were recorded. RESULTS: 11 patients were identified in 1988-2010. Patients received intravenous corticoid pulses in 64% of cases, followed by oral prednisone for a median of 6.6 months. They received a median of 12 PE sessions. BVAS, eGFR, and proteinuria improved significantly between baseline and the last PE at a median of 2 months. PE sessions were well tolerated, except in one patient who developed central catheter-associated septicemia. One patient required dialysis therapy 15 days after HSP diagnosis and did not recover kidney function. At the last medical evaluation at a mean follow-up of 6 years, median eGFR and proteinuria were 83 +/- 22 mL/min/1.73 m(2) and protein excretion of 140 +/- 10 mg/d, respectively. 3 women had pregnancy without complications. LIMITATIONS: This case series did not have a control group. CONCLUSIONS: The combination of PE and corticoid therapy in severe forms of HSP was associated with fast improvement and good long-term outcome. PMID- 22300650 TI - Decreased kidney function among agricultural workers in El Salvador. AB - BACKGROUND: An epidemic of chronic kidney disease of unknown cause has emerged along the Pacific coast of Central America, particularly in relatively young male sugarcane workers. In El Salvador, we examined residence and occupations at different altitudes as surrogate risk factors for heat stress. STUDY DESIGN: Cross-sectional population-based survey. SETTING & PARTICIPANTS: Populations aged 20-60 years of 5 communities in El Salvador, 256 men and 408 women (participation, 73%): 2 coastal communities with current sugarcane and past cotton production and 3 communities above 500 m with sugarcane, coffee, and service-oriented economies. PREDICTOR: Participant sex, age, residence, occupation, agricultural history by crop and altitude, and traditional risk factors for CKD. OUTCOMES: Serum creatinine (SCr) level greater than the normal laboratory range for sex, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, and proteinuria categorized as low (protein excretion >= 30-< 300 mg/dL) and high grade (>= 300 mg/dL). RESULTS: Of the men in the coastal communities, 30% had elevated SCr levels and 18% had eGFR < 60 mL/min/1.73 m2 compared with 4% and 1%, respectively, in the communities above 500 m. For agricultural workers, prevalences of elevated SCr levels and eGFR < 60 mL/min/1.73 m2 were highest for coastal sugarcane and cotton plantation workers, but were not increased in sugarcane workers at 500 m or subsistence farmers. Women followed a weaker but similar pattern. Proteinuria was infrequent, of low grade, and not different among communities, occupations, or sexes. The adjusted ORs of decreased kidney function for 10-year increments of coastal sugarcane or cotton plantation work were 3.1 (95% CI, 2.0-5.0) in men and 2.3 (95% CI, 1.4 3.7) in women. LIMITATIONS: The cross-sectional nature of the study limits etiologic interpretations. CONCLUSION: Agricultural work on lowland sugarcane and cotton plantations was associated with decreased kidney function in men and women, possibly related to strenuous work in hot environments with repeated volume depletion. PMID- 22300651 TI - Caries-preventive effect of sealants produced with altered glass-ionomer materials, after 2 years. AB - OBJECTIVES: The aim of the present study was to investigate the caries-preventive effect of sealants produced with a high-viscosity glass-ionomer with an elevated powder-liquid ratio (ART), of having energy added to this glass-ionomer, and that of glass-carbomer, in comparison to that of resin composite sealants. METHODS: The randomized controlled trial covered 407 children, with a mean age of 8 years. At a school compound three dentists placed sealants in pits and fissures of high caries-risk children. Evaluation by two independent evaluators was conducted after 0.5, 1 and 2 years. The Kaplan-Meier survival method, ANOVA and t-test were used in analyzing the data. RESULTS: 1352 first permanent molars were sealed. 6.6% of children and 6.8% of sealants dropped out within 2 years. 27 re-exposed pits and fissures, 20 in occlusal and 7 in smooth surfaces, in 25 children, developed a dentin carious lesion. The cumulative survival of dentin carious lesion-free pits and fissures in the glass-carbomer sealant group was statistically significantly lower (97.4%) than those in the high-viscosity glass ionomer with energy supplied (99%) and the resin-composite (98.9%) sealant groups. There was no statistically significant difference in the cumulative survival of dentin carious lesion-free pits and fissures, between the high viscosity glass-ionomer with (99%) and without (98.3%) energy supplied sealant groups, after 2 years. SIGNIFICANCE: The survival of dentin carious lesion-free pits and fissures was high in all sealant types. More dentin carious lesions were observed in the glass-carbomer sealant group. PMID- 22300652 TI - Plasma citrulline levels in preterm neonates with necrotizing enterocolitis. AB - BACKGROUND AND AIM: Citrulline is a non-protein amino acid synthesized in the small intestine. In children with short-bowel syndrome, citrulline has served as a reliable marker of the residual bowel length and parenteral nutrition (PN) independence. In the present study we aim to assess the value of citrulline measurement in preterm neonates developing necrotizing enterocolitis (NEC). METHODS: Plasma citrulline levels were measured prospectively in 17 preterm neonates with NEC stage II during the entire course of the disease. Serial citrulline determinations in 24 healthy preterm neonates on 2, 7, 14, 21 and 28 days of life (DOL), served as reference values. RESULTS: In healthy preterm neonates plasma citrulline levels showed a progressive increase in relation to age. In neonates presenting with NEC, mean citrulline levels were significantly lower as compared to controls' citrulline levels of the most approximate day of life (DOL 7: 16.85+/-4.2 vs 20.5+/-4.5 MUmol/L, p<0.05; DOL 14: 18+/-4.2 vs 23.5+/-4.3 MUmol/L, p<0.01; DOL 21: 17+/-2.5 vs 30+/-5.7 MUmol/L, p<0.01). The optimal citrulline cut-off distinguishing NEC patient from controls was 17.75 MUmol/L (sensitivity 76%, specificity 87%). Plasma citrulline at presentation correlated inversely with the duration of parenteral nutrition (r=-0.49, p<0.05). Consecutive citrulline determinations revealed that plasma citrulline increased during reintroduction and gradual increase of enteral nutrition. CONCLUSIONS: Our findings provide preliminary evidence that citrulline levels that are reduced in preterm neonates with NEC in comparison to age-matched controls and serial citrulline determinations could help to monitor improvement of functional enterocyte mass during the course and resolution of NEC. PMID- 22300653 TI - Advances in simultaneous DSC-FTIR microspectroscopy for rapid solid-state chemical stability studies: some dipeptide drugs as examples. AB - The solid-state chemistry of drugs has seen growing importance in the pharmaceutical industry for the development of useful API (active pharmaceutical ingredients) of drugs and stable dosage forms. The stability of drugs in various solid dosage forms is an important issue because solid dosage forms are the most common pharmaceutical formulation in clinical use. In solid-state stability studies of drugs, an ideal accelerated method must not only be selected by different complicated methods, but must also detect the formation of degraded product. In this review article, an analytical technique combining differential scanning calorimetry and Fourier-transform infrared (DSC-FTIR) microspectroscopy simulates the accelerated stability test, and simultaneously detects the decomposed products in real time. The pharmaceutical dipeptides aspartame hemihydrate, lisinopril dihydrate, and enalapril maleate either with or without Eudragit E were used as testing examples. This one-step simultaneous DSC-FTIR technique for real-time detection of diketopiperazine (DKP) directly evidenced the dehydration process and DKP formation as an impurity common in pharmaceutical dipeptides. DKP formation in various dipeptides determined by different analytical methods had been collected and compiled. Although many analytical methods have been applied, the combined DSC-FTIR technique is an easy and fast analytical method which not only can simulate the accelerated drug stability testing but also at the same time enable to explore phase transformation as well as degradation due to thermal-related reactions. This technique offers quick and proper interpretations. PMID- 22300654 TI - Temperature sensitivity of capillary-driven flow: application to age monitoring devices. AB - The effects of time-dependent temperature fluctuations on surface-tension driven fluid flow inside a capillary are modeled using classical hydrodynamics. To begin, Newton's second law is evoked to derive a nondimensional equation of motion that describes the time-evolution of the fluid front position and velocity as a function of system geometry, fluid properties, and fluid temperature. This model is used to examine how temperature excursions affect the instantaneous and long-term position and velocity of the fluid front inside the capillary. Next, the effects of orientation on the movement of high viscosity fluids through a capillary are examined. From these findings, a procedure is developed for designing non-powered time-temperature integration devices for recording the cumulative temperature exposure history of an environment. PMID- 22300655 TI - Common variable immunodeficiency (CVID): exploring the multiple dimensions of a heterogeneous disease. AB - Common variable immunodeficiency (CVID) represents a large heterogeneous group of antibody deficiency syndromes associated with a plethora of clinical features and as yet largely undefined molecular causes. We are now seeing this heterogeneous group being increasingly defined into single-gene and polygenic disorders after stratification into homogeneous patient subgroups based on improved clinical and immunological criteria, including molecular, functional, immunohistological, and longitudinal and outcome information. In this perspective, we highlight recent developments in CVID, addressing mainly its genetic and immunological dimensions. PMID- 22300656 TI - Detection of ganciclovir resistance mutations by pyrosequencing in HCMV-infected pediatric patients. AB - BACKGROUND: Human cytomegalovirus (HCMV) is an opportunistic pathogen especially for immuno-suppressed subjects that might develop pharmacological resistance in patients undergoing prolonged antiviral treatment. Ganciclovir (GCV) is the drug used as first choice therapy in affected children and a GCV-resistant phenotype is mainly linked to mutations of the viral protein kinase UL97. OBJECTIVES: Here a new quantitative pyrosequence (PSQ) method is presented that allows detection and quantification of the viral species carrying the more frequent UL97 mutations responsible for GCV resistance in clinical samples (>80% of known cases). STUDY DESIGN: The system has been validated using two independent approaches (cloning and sequencing of UL-97 gene fragments and real-time PCR) and clinical samples derived from 3 pediatric patients. RESULTS: The UL97 pyrosequencing analysis has indicated a significant increase of mutant viruses carrying the H520Q and C592G mutations. In particular, the H520Q viral mutation, known to increase GCV resistance (IC50=10) increased around 5 times during hospitalization. In addition, C592G (known to have IC50=2.9) also increased 3 times. CONCLUSIONS: PSQ is a quick, cheap, high throughput and sensitive analysis method to detect GCV associated resistance mutation useful to follow antiviral therapy in perinatal CMV-infection as well as in immune-suppressed patients. PMID- 22300657 TI - Hit to lead SAR study on benzoxazole derivatives for an NPY Y5 antagonist. AB - We report a hit to lead study on a novel benzoxazole NPY Y5 antagonist. Starting from HTS hit 1, structure-activity relationships were developed. Compound 12 showed reduction of food intake and a tendency to suppress body weight gain over the 21-day experimental period. PMID- 22300658 TI - The use of small molecule probes to study spatially separated stimulus-induced signaling pathways. AB - Simultaneous activation of signaling pathways requires dynamic assembly of higher order protein complexes at the cytoplasmic domains of membrane-associated receptors in a stimulus-specific manner. Here, using the paradigm of cellular activation through cytokine and innate immune receptors, we demonstrate the proof of-principle application of small molecule probes for the dissection of receptor proximal signaling processes, such as activation of the transcription factor NF kappaB and the protein kinase p38. PMID- 22300659 TI - Small molecule inhibitors of the HPV16-E6 interaction with caspase 8. AB - High-risk strains of human papillomaviruses (HPVs) cause nearly all cases of cervical cancer as well as a growing number of head and neck cancers. The oncogenicity of these viruses can be attributed to the activities of their two primary oncoproteins, E6 and E7. The E6 protein has among its functions the ability to prevent apoptosis of infected cells through its binding to FADD and caspase 8. A small molecule library was screened for candidates that could inhibit E6 binding to FADD and caspase 8. Flavonols were found to possess this activity with the rank order of myricetin>morin>quercetin>kaempferol=galangin?(apigenin, 7-hydroxyflavonol, rhamnetin, isorhamnetin, geraldol, datiscetin, fisetin, 6-hydroxyflavonol). Counter screening, where the ability of these chosen flavonols to inhibit caspase 8 binding to itself was assessed, demonstrated that myricetin, morin and quercetin inhibited GST-E6 and His-caspase 8 binding in a specific manner. The structure-activity relationships suggested by these data are unique and do not match prior reports on flavonols in the literature for a variety of anticancer assays. PMID- 22300660 TI - Adamantyl N-benzylbenzamide: new series of depigmentation agents with tyrosinase inhibitory activity. AB - A new series of polyhydroxylated N-benzylbenzamide derivatives containing an adamantyl moiety has been synthesized, and the depigmenting and tyrosinase inhibitory activities of the molecules were evaluated. The lipophilic character of the adamantyl moiety appeared to confer greater depigmentation power on the benzamide derivatives as compared to those lacking adamantyl substitution. Molecular modeling was applied in order to elucidate the interactions between ligands and tyrosinase that led to inhibition. PMID- 22300661 TI - Discovery of the first small molecule inhibitor of human DDX3 specifically designed to target the RNA binding site: towards the next generation HIV-1 inhibitors. AB - Efficacy of currently approved anti-HIV drugs is hampered by mutations of the viral enzymes, leading invariably to drug resistance and chemotherapy failure. Recent data suggest that cellular co-factors also represent useful targets for anti-HIV therapy. Here we describe the identification of the first small molecules specifically designed to inhibit the HIV-1 replication by targeting the RNA binding site of the human DEAD-Box RNA helicase DDX3. Optimization of a easily synthetically accessible hit (1) identified by application of a high throughput docking approach afforded the promising compounds 6 and 8 which proved to inhibit both the helicase and ATPase activity of DDX3 and to reduce the viral load of peripheral blood mononuclear cells (PBMC) infected with HIV-1. PMID- 22300663 TI - R-on-T and cardiac arrest from dual-chamber pacing without an atrial lead. PMID- 22300662 TI - Plasma BIN1 correlates with heart failure and predicts arrhythmia in patients with arrhythmogenic right ventricular cardiomyopathy. AB - BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder involving diseased cardiac muscle. Bridging integrator 1 (BIN1) is a membrane associated protein important to cardiomyocyte homeostasis and is downregulated in cardiomyopathy. We hypothesized that BIN1 could be released into the circulation and that blood-available BIN1 can provide useful data on the cardiac status of patients whose hearts are failing secondary to ARVC. OBJECTIVE: To determine whether plasma BIN1 levels can be used to measure disease severity in patients with ARVC. METHODS: We performed a retrospective cohort study of 24 patients with ARVC. Plasma BIN1 levels were assessed for their ability to correlate with cardiac functional status and predict ventricular arrhythmias. RESULTS: Mean plasma BIN1 levels were decreased in patients with ARVC with heart failure (15 +/ 7 vs 60 +/- 17 in patients without heart failure, P <.05; the plasma BIN1 level was 60 +/- 10 in non-ARVC normal controls). BIN1 levels correlated inversely with number of previous ventricular arrhythmia (R = -.47; P <.05), and low BIN1 levels correctly classified patients with advanced heart failure or ventricular arrhythmia (receiver operator curve area under the curve of 0.88 +/- 0.07). Low BIN1 levels also predicted future ventricular arrhythmias (receiver operator curve area under the curve of 0.89 +/- 0.09). In a stratified analysis, BIN1 levels could predict future arrhythmias in patients without severe heart failure (n = 20) with an accuracy of 82%. In the 7 patients with ARVC with serial blood samples, all of whom had evidence of disease progression during follow-up, plasma BIN1 levels decreased significantly (a decrease of 63%; P <.05). CONCLUSIONS: Plasma BIN1 level seems to correlate with cardiac functional status and the presence or absence of sustained ventricular arrhythmias in a small cohort of patients with ARVC and can predict future ventricular arrhythmias. PMID- 22300664 TI - The phenomenon of "QT stunning": the abnormal QT prolongation provoked by standing persists even as the heart rate returns to normal in patients with long QT syndrome. AB - BACKGROUND: Patients with long QT syndrome (LQTS) have inadequate shortening of the QT interval in response to the sudden heart rate accelerations provoked by standing-a phenomenon of diagnostic value. We now validate our original observations in a cohort twice as large. We also describe that this abnormal QT interval response persists as the heart rate acceleration returns to baseline. OBJECTIVES: To describe a novel observation, termed "QT stunning" and to validate previous observations regarding the "QT-stretching" phenomenon in patients with LQTS by using our recently described "standing test." METHODS: The electrocardiograms of 108 patients with LQTS and 112 healthy subjects were recorded in the supine position. Subjects were then instructed to stand up quickly and remain standing for 5 minutes during continuous electrocardiographic recording. The corrected QT interval was measured at baseline (QTc(base)), when heart rate acceleration without appropriate QT-interval shortening leads to maximal QT stretching (QTc(stretch)) and upon return of heart rate to baseline (QTc(return)). RESULTS: QTc(stretch) lengthened significantly more in patients with LQTS (103 +/- 80 ms vs 66 +/- 40 ms in controls; P <.001) and so did QTc(return) (28 +/- 48 ms for patients with LQTS vs -3 +/- 32 ms for controls; P <.001). Using a sensitivity cutoff of 90%, the specificity for diagnosing LQTS was 74% for QTc(base), 84% for QTc(return), and 87% for QTc(stretch). CONCLUSIONS: The present study extends our previous findings on the abnormal response of the QT interval in response to standing in patients with LQTS. Our study also shows that this abnormal response persists even after the heart rate slows back to baseline. PMID- 22300665 TI - EGFR, CD10 and proliferation marker Ki67 expression in ameloblastoma: possible role in local recurrence. AB - BACKGROUND: Ameloblastoma is an odontogenic neoplasm characterized by local invasiveness and tendency towards recurrence. AIMS: Studying the role played by EGFR, CD10 and Ki67 in the recurrence of ameloblastoma. METHODS: This study was carried out on 22 retrospective cases of mandibular ameloblastoma from the period from Jan 2002 to Jan 2008 with follow up period until Jan 2011 (3 to 8 years follow up peroid). Archival materials were obtained from pathology department, Mansoura university. Paraffin sections of tumor tissue from all cases were submitted for routine H&E stains and immunohistochemistry using EGFR, CD10 and Ki67 monoclonal antibodies. Statistical analysis using of clinical data for all patients, tumor type, EGFR, CD10 and Ki67 expression in relation to recurrence were evaluated. RESULTS: Among the 22 cases, 10 cases were males and 12 were females with sex ratio 1:1.2. Age ranged from 34 to 59 years old with a mean age 44.18 year. Five cases showed local recurrence within studied period and proved by biopsy. No statistically significant relation was found between local recurrence and patient age, tumor size, tumor type, EGFR expression. There was a significant relation between CD10 expression as well as Ki67 labelling index and recurrence (P value = 0.003, 0.000 respectively). CONCLUSION: Evaluation of CD10 and Ki67 status together with conventional histological evaluation can help in providing more information about the biologic behavior of the tumor, while EGFR could be a target of an expanding class of anticancer therapies. Since ameloblastomas are EGFR-positive tumors, anti-EGFR agents could be considered to reduce the size of large tumors and to treat unresectable tumors that are in close proximity to vital structures. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1902106905645651. PMID- 22300666 TI - Neurodevelopmental functioning in very young children undergoing treatment for non-CNS cancers. AB - OBJECTIVE: We initiated a prospective study of very young children with cancer, in comparison with matched healthy children, to investigate neurodevelopmental consequences of non-CNS cancers and treatment. METHODS: A total of 61 children (<=42 months) with non-CNS cancers and 61 matched controls underwent an identical age-appropriate neuropsychological test battery. RESULTS: Children with cancer manifested deficits compared to healthy controls in motor, mental, and language development, but were similar to controls in cognitive representational abilities and emotional relationships in interaction with their mothers. Better physician rated health status at diagnosis and mother-rated behavioral status 1 month prior to assessment were associated with better motor and mental performance in the cancer group. CONCLUSIONS: This study identifies deficits as well as spared functions in children with non-CNS cancers; the results suggest ways parents and healthcare professionals may plan specific remediations to enhance quality of life in young cancer survivors. PMID- 22300668 TI - GluN1 hypomorph mice exhibit wide-ranging behavioral alterations. AB - The psychotomimetic effects of N-methyl-d-aspartate receptor (NMDA) antagonists such as ketamine and phencyclidine suggest a role for reduced NMDA receptor mediated neurotransmission in schizophrenia. GluN1 'hypomorph' (GluN1(hypo) ) mice exhibit reduced NMDA receptor expression and have been suggested as a mouse model of schizophrenia. However, NMDA receptors are ubiquitous and are implicated in many physiological and pathological processes. The GluN1(hypo) mice have a global reduction of NMDA receptors and the consequences of such a global manipulation are likely to be wide-ranging. We therefore assessed GluN1(hypo) mice on a battery of behavioral tests, including tests of naturalistic behaviors, anxiety and cognition. GluN1(hypo) mice exhibited impairments on all tests of cognition that we employed, as well as reduced engagement in naturalistic behaviors, including nesting and burrowing. Behavioral deficits were present in both spatial and non-spatial domains, and included deficits on both short- and long-term memory tasks. Results from anxiety tests did not give a clear overall picture. This may be the result of confounds such as the profound hyperactivity seen in GluN1(hypo) mice, although hyperactivity cannot account for all of the results obtained. When viewed against this background of far-reaching behavioral abnormalities, the specificity of any one behavioral deficit is inevitably called into question. Indeed, the present data from GluN1(hypo) mice are indicative of a global impairment rather than any specific disease. The deficits seen go beyond what one would expect from a mouse model of schizophrenia, thus questioning their utility as a selective model of this disease. PMID- 22300669 TI - Depersonalised doctors: a cross-sectional study of 564 doctors, 760 consultations and 1876 patient reports in UK general practice. AB - OBJECTIVES: The objectives of this study were to assess burnout in a sample of general practitioners (GPs), to determine factors associated with depersonalisation and to investigate its impact on doctors' consultations with patients. DESIGN: Cross-sectional, postal survey of GPs using the Maslach Burnout Inventory (MBI). Patient survey and tape-recording of consultations for a subsample of respondents stratified by their MBI scores, gender and duration of General Medical Council registration. SETTING: UK general practice. PARTICIPANTS: GPs within NHS Essex. PRIMARY AND SECONDARY OUTCOME MEASURES: Scores on MBI subscales (depersonalisation, emotional exhaustion, personal accomplishment); scores on Doctors' Interpersonal Skills Questionnaire and patient-centredness scores attributed to tape-recorded consultations by independent observers. RESULTS: In the postal survey, 564/789 (71%) GPs completed the MBI. High levels of emotional exhaustion (261/564 doctors, 46%) and depersonalisation (237 doctors, 42%) and low levels of personal accomplishment (190 doctors, 34%) were reported. Depersonalisation scores were related to characteristics of the doctor and the practice. Male doctors reported significantly higher (p<0.001) depersonalisation than female doctors. Doctors registered with the General Medical Council under 20 years had significantly higher (p=0.005) depersonalisation scores than those registered for longer. Doctors in group practices had significantly higher (p=0.001) depersonalisation scores than single handed practitioners. Thirty-eight doctors agreed to complete the patient survey (n=1876 patients) and audio-record consultations (n=760 consultations). Depersonalised doctors were significantly more likely (p=0.03) to consult with patients who reported seeing their 'usual doctor'. There were no significant associations between doctors' depersonalisation and their patient-rated interpersonal skills or observed patient-centredness. CONCLUSIONS: This is the largest number of doctors completing the MBI with the highest levels of depersonalisation reported. Despite experiencing substantial depersonalisation, doctors' feelings of burnout were not detected by patients or independent observers. Such levels of burnout are, however, worrying and imply a need for action by doctors themselves, their medical colleagues, professional bodies, healthcare organisations and the Department of Health. PMID- 22300670 TI - Iowa gambling task performance in overweight children and adolescents at risk for obstructive sleep apnea. AB - Obstructive sleep apnea (OSA) is a nocturnal respiratory disorder associated with cognitive and behavioral sequelae, including impairments in executive functioning (EF). Previous literature has focused on "cool" EF, meaning abilities such as working memory and planning that do not involve affective control requirements. Little is known about the impact OSA may have on "hot" EF that involves regulation of affect and risk-related decision-making, and that may be particularly salient during adolescence, when these skills are rapidly developing. This study examined performance on the Iowa Gambling Task (IGT), a task believed to assess aspects of "hot" EF, in overweight adolescents at risk for OSA. Consistent with hypotheses, individuals without OSA made more beneficial decisions on the IGT over time, but participants with OSA did not benefit from feedback and continued to make choices associated with higher initial rewards, but greater long-term losses. The relationship between developmental level and IGT performance was moderated by OSA status. Individuals with OSA did not demonstrate the expected developmental gains in performance during the IGT. This finding suggests that OSA may impact the development of critical aspects of EF, or at least the expression of these skills during the developmentally important period of adolescence. PMID- 22300671 TI - New opportunities in challenging times: but we need to act now. PMID- 22300675 TI - Testing the evolvability of an insect carboxylesterase for the detoxification of synthetic pyrethroid insecticides. AB - Esterases have been implicated in metabolic resistance to synthetic pyrethroids in several insect species but little is yet known of the molecular basis for these effects. In this work modern directed evolution technology was used to test to what extent it is possible to genetically enhance the pyrethroid hydrolytic activity of the E3 carboxylesterase from the blowfly Lucilia cuprina. High throughput screening of a random mutant library with individual stereoisomers of fluorogenic analogues of two type II pyrethroids identified 17 promising variants that were then also tested with the commercial pyrethroid deltamethrin. Between them, these variants displayed significantly improved activities for all the substrates tested. Amino acid substitutions at ten different residues were clearly implicated in the improvements, although most only enhanced activity for a subset of the stereoisomers. Several new combinations of the most promising amino acid substitutions were then made, and negative epistatic effects were found in most of the combinations, but significant improvements were also found in a minority of them. The best mutant recovered contained three amino acid changes and hydrolysed deltamethrin at more than 100 times the rate of wild-type E3. Structural analysis shows that nine of the ten mutated residues improving pyrethroid or analogue activities cluster in putative substrate binding pockets in the active site, with the three mutations of largest effect all increasing the volume of the acyl pocket. PMID- 22300676 TI - Variation in maternal and anxiety-like behavior associated with discrete patterns of oxytocin and vasopressin 1a receptor density in the lateral septum. AB - The relationship between anxiety and maternal behavior has been explored across species using a variety of approaches, yet there is no clear consensus on the nature or direction of this relationship. In the current study, we have assessed stable individual differences in anxiety-like behavior in a large cohort (n=57) of female F2 hybrid mice. Using open-field behavior as a continuous and categorical (high vs. low) measure we examined the relationship between the anxiety-like behavior of virgin F2 females and the subsequent maternal behavior of these females. In addition, we quantified oxytocin (OTR) and vasopressin (V1a) receptor density within the lateral septum to determine the possible correlation with anxiety-like and maternal behavior. We find that, though activity levels within the open-field do predict latency to engage in pup retrieval, anxiety-like measures on this test are otherwise not associated with subsequent maternal behavior. OTR density in the dorsal lateral septum was found to be negatively correlated with activity levels in the open-field and positively correlated with frequency of nursing behavior. V1a receptor density was significantly correlated with postpartum licking/grooming of pups. Though we do not find support for the hypothesis that individual differences in trait anxiety predict variation in maternal behavior, we do find evidence for the role of OTR and V1a receptors in predicting maternal behavior in mice and suggest possible methodological issues (such as distinguishing between trait and state anxiety) that will be a critical consideration for subsequent studies of the anxiety-maternal behavior relationship. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior. PMID- 22300677 TI - Industry influenced evidence production in collaborative research communities: a network analysis. AB - OBJECTIVE: To measure the relative influence that industry authors have on collaborative research communities and evidence production. STUDY DESIGN AND SETTING: Using 22 commonly prescribed drugs, 6,711 randomized controlled trials (RCTs), and 28,104 authors, 22 collaboration networks were constructed and analyzed. The directly industry-affiliated (DIA) authors were identified in the networks according to their published affiliations. Measures of influence (network centrality) and impact (citations) were determined for every author. Network-level measures of community structure and collaborative preference were used to further characterize the groups. RESULTS: Six percent (1,741 of 28,104) of authors listed a direct affiliation with the manufacturer of a drug evaluated in the RCT. These authors received significantly more citations (P<0.05 in 19 networks) and were significantly more central in the networks (P<0.05 in 20 networks). The networks show that DIA authors tend to have greater reach in the networks and collaborate more often with non-DIA authors despite a preference toward their own group. Potential confounders include publication bias, trial sizes, and conclusions. CONCLUSIONS: Industry-based authors are more central in their networks and are deeply embedded within highly connected drug research communities. As a consequence, they have the potential to influence information flow in the production of evidence. PMID- 22300678 TI - Gendered pathways in school burnout among adolescents. AB - The aim of this study is to examine differences in student burnout by gender, time status with two time points before and after an educational transition, and educational track (academic vs. vocational). The definition of burnout is based on three components: exhaustion due to school demands, a disengaged and cynical attitude toward school, and feelings of inadequacy as a student (Salmela-Aro, Kiuru, Leskinen, & Nurmi, 2009). A total of 770 Finnish adolescents (M age = 16) were examined at the beginning of their last year in comprehensive school, and three times annually during their secondary education both on academic and vocational tracks. Among boys on the academic track, overall school burnout and its three components, exhaustion, cynicism and inadequacy, increased, whereas among boys on the vocational track, no changes in school burnout emerged. Among girls on the academic track, overall school burnout and inadequacy increased, whereas among girls on the vocational track, cynicism decreased. Finally, school burnout was highest among girls on the academic track, but increased most among boys on the academic track. PMID- 22300679 TI - Plasma lipoprotein-associated phospholipase A2 is inversely correlated with proprotein convertase subtilisin-kexin type 9. AB - BACKGROUND AND AIMS: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a pro-atherogenic phospholipase A(2), which is predominantly complexed to low density lipoprotein (LDL) particles. Proprotein convertase subtilisin-kexin type 9 (PCSK9) provides a key step in LDL metabolism by stimulating LDL receptor degradation. We determined relationships between plasma PCSK9 and Lp-PLA(2) mass. METHODS: Lp-PLA(2) mass (turbidimetric immunoassay), PCSK9 (enzyme-linked immunosorbent assay) and (apo) lipoproteins were measured in 53 nondiabetic subjects (27 women) with body mass index <30 kg/m(2). RESULTS: Lp-PLA(2) and PCSK9 levels were both correlated positively with LDL cholesterol and non-high density lipoprotein (HDL) cholesterol (r = 0.330 to r = 0.382, p <=0.02). Remarkably, Lp-PLA(2) was inversely related to PCSK9 (r = -0.388, p = 0.004). The Lp-PLA(2)/apolipoprotein B ratio, as a measure of the Lp-PLA(2) content in apolipoprotein B-containing lipoproteins, was also inversely correlated with PCSK9 (r = -0.575, p <0.001). The inverse relationships of Lp-PLA(2) (p = 0.023) and the Lp-PLA(2)/apolipoprotein B ratio (p = 0.001) with PCSK9 levels remained significant after controlling for age, gender, triglycerides and HDL cholesterol. CONCLUSIONS: Despite increasing effects on LDL cholesterol, higher PCSK9 levels are unlikely to confer impaired Lp-PLA(2) metabolism. We propose to evaluate the possible influence of PCSK9 inhibiting strategies on Lp-PLA(2) regulation and vice versa to determine effects of Lp-PLA(2) inhibitors on the PCSK9 pathway. PMID- 22300680 TI - Identification of the mutations in the tissue-nonspecific alkaline phosphatase gene in two Chinese families with hypophosphatasia. AB - BACKGROUND AND AIMS: Hypophosphatasia is a genetic disorder characterized by defective bone and tooth mineralization and a deficiency of serum and bone alkaline phosphatase activity. To date, few studies have identified gene mutations in Chinese patients with hypophosphatasia. We sought to characterize the clinical manifestations and identify the mutations associated with the disease in Chinese hypophosphatasia patients. METHODS: All 12 exons and the exon intron boundaries of the ALPL gene were amplified and directly sequenced in two probands from unrelated Chinese families. The mutation sites were identified in other unaffected members of these two families and 100 healthy controls. RESULTS: In family 1, the proband displayed one novel splice site mutation, c.298-1G>A, which consisted of a homozygous G>A transition at nucleotide 298-1 in intron 4. The proband's mother displayed the heterozygous G/A ALPL gene mutation, but her father was identified as G/G homozygous. A paternity test ruled out false paternity and therefore confirmed that this splicing mutation occurred de novo either in the paternal germline or in the early development of the patient. In family 2, the proband revealed a novel missense mutation (c.1271T>C) in exon 11, which resulted in p.Val424Ala in the mature ALPL polypeptide. Furthermore, c.298 1G>A and c.1271T>C mutations were not found in unaffected family members of these two Chinese families and 100 unrelated controls. CONCLUSIONS: Our study shows that the novel de novo splicing mutation c.298-1G>A in intron 4 and the missense mutation c.1271T>C in exon 11 of the ALPL gene are responsible for hypophosphatasia in some Chinese patients. PMID- 22300681 TI - Production of IL-10, TNF and IL-12 by peripheral blood mononuclear cells in Mexican workers exposed to a mixture of benzene-toluene-xylene. AB - BACKGROUND AND AIMS: Occupational exposure to low-level benzene and the joint action of toluene-xylene probably cause effects on circulating monocytes immune response. We undertook this study to determine relationship between occupational exposure to benzene-toluene-xylene mixture (BTX) and IL-10, TNF and IL-12 production by peripheral blood mononuclear cells. METHODS: Exposure was estimated in 54 workers from a paint company in Mexico City through BTX accumulated potential dose (BTX-APD). Two exposure groups were formed: high and low BTX-APD established with a cutoff point at >=1.0 of BTX-APD, as a function of the geometric mean of the estimator's value distribution and the higher agreement between BTX-APD >=1.0 and the areas referred as using (or not) organic solvents in the work process. IL-10, TNF and IL-12 concentrations were measured with ELISA. Through multiple linear regression models, the production of each of the proposed cytokines and of the whole set was assessed. RESULTS: Workers with high BTX-APD showed a significant reduction in TNF production (beta = -1,196.0 pg/mL; p = 0.01); a reduction for IL-10 (beta = -520.3; p = 0.13) and IL-12 (beta = 843.3; p = 0.09) was also observed, although without statistical significance. CONCLUSIONS: TNF production assessed in workers with a high BTX-APD is lower than in those with a low BTX-APD, but not in IL-10 and IL-12 production. PMID- 22300682 TI - Serum chemokines RANTES and monocyte chemoattractant protein-1 in Egyptian patients with atopic asthma: relationship to disease severity. AB - BACKGROUND AND AIMS: Asthma is a highly prevalent, complex inflammatory disease of the airways often associated with bronchial hyperreactivity and atopy. The chemokine RANTES (regulated upon activation, normal T -cell expressed and secreted) is an important element for the chemotaxis at the site of allergic inflammation. This study aimed to assess the serum levels of the chemokines RANTES and monocyte chemoattractant protein-1 (MCP-1) in Egyptian patients with atopic asthma and to evaluate their possible relation t the severity of airway obstruction. METHODS: The study included 60 Egyptian patients with atopic asthma and 20 healthy volunteers. Serum levels of the chemokines RANTES and MCP-1 were measured. Total serum IgE level and absolute eosinophil counts were determined. The severity of airway obstruction was assessed using spirometric measurement (FEV(1)). RESULTS: The serum levels of RANTES were significantly higher in all asthmatic patients than the controls (p <0.001). Moreover, RANTES levels were significantly increased in patients with moderate and severe asthma as compared to those with mild asthma (p <0.001). Serum RANTES correlated positively with absolute eosinophil counts and total serum IgE and negatively with FEV(1), whereas there was no significant correlation with serum MCP-1 in all asthmatic patients. CONCLUSIONS: Serum RANTES may be used as a useful noninvasive marker of airway obstruction and a potential diagnostic tool for monitoring asthma severity. In this regard, identification and blocking of this chemokine and/or its receptor may be a promising therapeutic approach to asthmatic patients. PMID- 22300683 TI - Impact of testosterone on the expression of organic anion transporting polypeptides (OATP-1A2, OATP-2B1, OATP-3A1) in malignant and non-malignant human breast cells in vitro. AB - OBJECTIVES: Postmenopausal hormone therapy (HT) increases local estrogen formation in breast tissue. The enzymatic substrates depend on transmembrane anion transporting polypeptides (OATPs) to reach intracellular enzymes. The aim of this study was to investigate the effect of testosterone (T) on the expression of OATP-1A2, OATP-2B1, and OATP-3A1 in malignant (MCF-7, BT-474) and non malignant (HBL-100) breast cells in vitro. STUDY DESIGN: Cells were incubated in RPMI 1640 medium containing 5% steroid-depleted fetal calf serum for 3d, and subsequently incubated in the absence or presence of T, anastrozole (A), and T+A (10(-6)M) for 24h at 37 degrees C. MAIN OUTCOME MEASURES: OATP expression was determined by immunocytochemical staining. Expression intensity was graded as low, moderate, or strong. Hormone receptor (AR, PR, ESR1, ESR2) expression was investigated by qPCR and Western blotting. Rank variance analysis was performed for statistical analysis (p<=0.05). RESULTS: OATP-1A2, OATP-2B1, and OATP-3A1 expression was present in all untreated breast cell lines examined, with OATP-1A2 and OATP-3A1 being the predominant ones. There was a trend for a higher baseline expression in untreated HBL-100 and BT-474 in comparison to MCF-7 cells, which was significant for OATP-2B1. T treatment led to decreased OATP-1A2, -2B1, and 3A1 expression in BT-474 and HBL-100 cells, respectively. In contrast, in MCF-7 cells, OATP-2B1 expression was significantly increased. T-induced upregulation of AR and PR protein expression in BT-474 and MCF-7 cells was reduced by A treatment. CONCLUSIONS: T may constitute a signal for differential regulation of mammary OATP expression. In non-malignant breast cells T seems to have a beneficial effect by reducing the availability of substrates for the intracellular formation of potent estrogens. PMID- 22300684 TI - Primary ovarian insufficiency: relation to changes in body composition and adiposity. AB - There are several causes of primary ovarian insufficiency (POI) but all result in a premature cessation of female reproductive potential, mimicking the normal menopause. In normal menopause, there is increased cardiovascular risk associated with changes in body composition (specifically increasing adiposity). We sought to review the literature on POI in relation to changes in adiposity and related cardiometabolic risk factors. We conclude that POI patients are usually less obese than reference groups. PMID- 22300685 TI - Stopping menopausal hormone therapy: if breast cancer really decreased, why did colorectal cancer not increase? AB - OBJECTIVE: The Women's Health Initiative (WHI) study of postmenopausal hormone therapy (HT) found that estrogen plus progestogen therapy (EPT) decreased colorectal cancer risk. Thus, the decline in EPT use from 2002 to 2003 should have precipitated an increase in the incidence of colorectal cancer. We tested this prediction using the SEER 9 epidemiologic database. METHODS: We analyzed WHI data concerning the effects of EPT and estrogen therapy (ET) on colorectal cancer risks. We also examined HT prescription sales data, as well as SEER 9 colorectal cancer incidences from 2001 to 2004. RESULTS: In the WHI study, the incidence of colorectal cancer was comparable in EPT placebo-users, ET users, and ET placebo users, but significantly lower in EPT users. Assuming that 30% of eligible women used HT in 2001, the decline in EPT sales from 2002 to 2003 of 63% should have increased the incidence of colorectal cancer by 2.8% in the overall population at risk. However, the SEER 9 colorectal cancer incidence fell by 5.9% in this population, which is comparable to the 6.7% decrease observed for invasive breast cancer from 2002 to 2003. CONCLUSIONS: Declining EPT use from 2002 to 2003 should have precipitated an increase in the incidence of colorectal cancer, but the opposite trend was seen in the SEER 9 database during this time. The incidences of invasive breast cancer and colorectal cancer both declined by a similar amount from 2002 to 2003, despite the results of the WHI study predicting opposing trends for the two different types of cancer. Thus, the SEER 9 findings are fundamentally incompatible with expectations from the WHI findings. This implies that reductions in HT use from 2002 to 2003 cannot account for the contemporaneous changes in invasive breast cancer and colorectal cancer incidences. Alternative explanations must be found. PMID- 22300686 TI - Incidence of nonunion of the unfixated, isolated evans calcaneal osteotomy: a systematic review. AB - The Evans calcaneal osteotomy is frequently implemented in flatfoot reconstructive surgery for correction of planar deformity. Rigid fixation across an osteotomy is a documented, accepted technique to gain stability. However, since the original description of this osteotomy, which involved no internal fixation, debate has existed regarding the necessity of fixation. Conventional wisdom suggests that the nonunion rate would increase with an unfixated osteotomy. Thus, in an effort to determine the incidence of nonunion of the unfixated, isolated Evans calcaneal osteotomy, we conducted a systematic review. Studies were eligible for inclusion only if they included the following: the nonunion rate for unfixated, isolated Evans calcaneal osteotomy, follow-up of at least 1 year and a sample size of at least 5 feet. After considering all potentially eligible studies, 2 evidence-based medicine level 2 and 3 evidence based medicine level 3 studies met our inclusion criteria. A total of 73 feet, with a weighted mean age of 22.6 years, were included. The weighted mean follow up of the included studies was 3.6 years. A total of 1 nonunion (1.4%) was reported. The results of our systematic review revealed an acceptably low rate of nonunion for the unfixated, isolated Evans calcaneal osteotomy. However, considering the limited data available, additional prospective investigations are warranted to further validate the nonunion rate with this technique. PMID- 22300687 TI - Automatic detection and analysis of the EEG sharp wave-slow wave patterns evoked by fluorinated inhalation anesthetics. AB - OBJECTIVE: The aim of this study was to develop a method for the automatic detection of sharp wave-slow wave (SWSW) patterns evoked in EEG by volatile anesthetics and to identify the patterns' characteristics. METHODS: The proposed method consisted in the k-NN classification with a reference set obtained using expert knowledge, the morphology of the EEG patterns and the condition for their synchronization. The decision rules were constructed and evaluated using 24h EEG records in ten patients. RESULTS: The sensitivity, specificity and selectivity of the method were 0.88 +/- 0.10, 0.81 +/- 0.13 and 0.42 +/- 0.16, respectively. SWSW patterns' recruitment was strictly dependent on anesthetic concentration. SWSW patterns evoked by different types of anesthetics expressed different characteristics. CONCLUSIONS: Synchronization criterion and adequately selected morphological features of "slow wave" were sufficient to achieve the high sensitivity and specificity of the method. SIGNIFICANCE: The monitoring of SWSW patterns is important in view of possible side effects of volatile anesthetics. The analysis of SWSW patterns' recruitment and morphology could be helpful in the diagnosis of the anesthesia effects on the CNS. PMID- 22300688 TI - A longitudinal study on diarrhoea and vomiting in young dogs of four large breeds. AB - BACKGROUND: Prospective studies to document the occurrence of canine diarrhoea and vomiting are relatively scarce in dogs, and the majority of published studies are based on information from clinical records. This study investigates the incidence risk of diarrhoea and vomiting as well as potential risk factors. METHODS: A cohort study of 585 privately owned dogs of four breeds: Newfoundland, Labrador retriever, Leonberger, and Irish wolfhound. The owners maintained a continuous log regarding housing, exercise, nutrition, and health of their dogs. Episodes of diarrhoea and vomiting were recorded in a consecutive manner in a booklet. The owners completed the questionnaires and reported information at three, four, six, 12, 18, and 24/25 months of age, called observational ages.Associations with potential risk factors for diarrhoea and vomiting were investigated in separate generalized estimating equation analyses. RESULTS: The incidence of both diarrhoea and vomiting was influenced by breed. Both diarrhoea and vomiting were relatively common in young dogs, occurring most frequently during the first months of life. After three months of age, the odds of diarrhoea were significantly lower when compared to the observational period seven weeks to three months (OR ranging from 0.31 to 0.70 depending on the period). More males than females suffered from diarrhoea (OR = 1.42). The occurrence of diarrhoea was more common in dogs that also experienced episode(s) of vomiting during the study period (OR = 5.43) and vice versa (OR = 5.50). In the majority of dogs episodes of diarrhoea and vomiting did not occur at the same time. Dogs in urban areas had higher odds (OR = 1.88) of getting diarrhoea compared to dogs living in rural areas. The occurrence of both diarrhoea and vomiting demonstrated a seasonal variation with higher incidence during the summer months. CONCLUSION: Both diarrhoea and vomiting occurred most frequently during the first months of life. The incidence of diarrhoea and vomiting was significantly different between breeds. Diarrhoea occurred more frequently in males and in dogs living in urban areas. Also, a positive association between the occurrence of diarrhoea and vomiting in the same dog was found. PMID- 22300689 TI - Effects of radiation exposure from cardiac imaging: how good are the data? AB - Concerns about medical exposure to ionizing radiation have become heightened in recent years as a result of rapid growth in procedure volumes and the high radiation doses incurred from some procedures. This paper summarizes the evidence base undergirding concerns about radiation exposure in cardiac imaging. After classifying radiation effects, explaining terminology used to quantify the radiation received by patients, and describing typical doses from cardiac imaging procedures, this paper will address the major epidemiological studies having bearing on radiation effects at doses comparable to those received by patients undergoing cardiac imaging. These include studies of atomic bomb survivors, nuclear industry workers, and children exposed in utero to x-rays, all of which have evidenced increased cancer risks at low doses. Additional higher-dose epidemiological studies of cohorts exposed to radiation in the context of medical treatment are described and found to be generally compatible with these cardiac dose-level studies, albeit with exceptions. Using risk projection models developed by the U.S. National Academies that incorporate these data and reflect several evidence-based assumptions, cancer risk from cardiac imaging can be estimated and compared with the benefits from imaging. Several ongoing epidemiological studies will provide better understanding of radiation-associated cancer risks. PMID- 22300690 TI - Sex-related differences in clinical presentation and outcome of transcatheter aortic valve implantation for severe aortic stenosis. AB - OBJECTIVES: The purpose of this study was to clarify the impact of sex-related differences in transcatheter aortic valve implantation (TAVI) for high-risk patients with severe aortic stenosis. BACKGROUND: Although TAVI is becoming a mature technique, the impact of sex differences remains unclear. METHODS: The TAVI patients were included prospectively in a dedicated database from October 2006. The proportion of women (n = 131) was similar to that of men (n = 129). The Edwards valve (85.4%) and CoreValve (14.6%) were used through the transfemoral (65.0%), subclavian (3.1%), or transapical (31.9%) approach. All events were defined according to Valve Academic Research Consortium criteria. RESULTS: Age was similar (83.1 +/- 6.3 years), but women had less coronary and peripheral disease, less previous cardiac surgery, higher ejection fraction, and lower EuroSCORE (European System for Cardiac Operative Risk Evaluation [22.3 +/- 9.0% vs. 26.2 +/- 13.0%, p = 0.005]). Minimal femoral size (7.74 +/- 1.03 mm vs. 8.55 +/- 1.34 mm, p < 0.001), annulus size (20.9 +/- 1.4 vs. 22.9 +/- 1.7 mm, p < 0.001), and valve size (23.9 +/- 1.6 mm vs. 26.3 +/- 1.5 mm, p < 0.001) were smaller in women. Device success was similar (90.8% vs. 88.4%, p = 0.516) despite more frequent iliac complications (9.0% vs. 2.5%, p = 0.030). Residual mean aortic pressure gradient (11.6 +/- 4.9 vs. 10.9 +/- 4.9, p = 0.279) was also similar. The 1-year survival rate was higher for women, 76% (95% confidence interval: 72% to 80%), than for men, 65% (95% confidence interval: 60% to 69%); and male sex (hazard ratio: 1.62, 95% confidence interval: 1.03 to 2.53, p = 0.037) was identified as a predictor of midterm mortality by Cox regression analysis. CONCLUSIONS: Female sex is associated with better baseline clinical characteristics and improved survival, and is identified as a predictor of midterm survival after TAVI. PMID- 22300691 TI - Meta-analysis of statin effects in women versus men. AB - OBJECTIVES: The aim of this study was to evaluate the effect of statins in decreasing cardiovascular events in women and men. BACKGROUND: Published data reviews have suggested that statins might not be as effective in women as in men in decreasing cardiovascular events. METHODS: Published data searches and contacts with investigators identified 18 randomized clinical trials of statins with sex-specific outcomes (N = 141,235, 40,275 women, 21,468 cardiovascular events). Odds ratios (ORs) and 95% confidence intervals (CIs) for cardiovascular events were calculated for women and men separately with random effects meta analyses. RESULTS: The cardiovascular event rate was lower among those randomized to statin intervention than in those randomized to control (low-dose statin in 4 studies, placebo in 11 studies, usual care in 3 studies) and similar in women and men (OR: 0.81, 95% CI: 0.75 to 0.89; p < 0.0001, and OR: 0.77, 95% CI: 0.71 to 0.83, p < 0.0001, respectively). The benefit of statins was statistically significant in both sexes, regardless of the type of control, baseline risk, or type of endpoint and in both primary and secondary prevention. All-cause mortality was also lower with statin therapy both in women and men without significant interaction by sex (p for interaction = 0.4457). CONCLUSIONS: Statin therapy is associated with significant decreases in cardiovascular events and in all-cause mortality in women and men. Statin therapy should be used in appropriate patients without regard to sex. PMID- 22300692 TI - Controversy and consensus about statin use: it is not about the sex. PMID- 22300693 TI - Ursodeoxycholic acid in patients with chronic heart failure: a double-blind, randomized, placebo-controlled, crossover trial. AB - OBJECTIVES: This study sought to assess the effects of ursodeoxycholic acid (UDCA) on endothelial function and inflammatory markers in patients with chronic heart failure (CHF). BACKGROUND: Endothelial dysfunction is commonly observed in patients with CHF, and it contributes to the limitation in exercise capacity that accompanies this condition. Bacterial lipopolysaccharide may trigger proinflammatory cytokine release and promote further endothelial dysfunction. UDCA, a bile acid used in the treatment of cholestatic liver disease, has anti inflammatory and cytoprotective properties and may contribute to the formation of mixed micelles around lipopolysaccharide. These properties may help to improve peripheral blood flow in patients with CHF. METHODS: We performed a prospective, single-center, double-blind, randomized, placebo-controlled crossover study of UDCA in 17 clinically stable male patients with CHF (New York Heart Association functional class II/III, left ventricular ejection fraction <45%). Patients received in random order 500 mg UDCA twice daily for 4 weeks and placebo for another 4 weeks. The primary endpoint was post-ischemic peak peripheral arm blood flow as assessed by strain-gauge plethysmography. RESULTS: Sixteen patients completed the study. UDCA was well tolerated in all patients. Compared with placebo, UDCA improved peak post-ischemic blood flow in the arm (+18%, p = 0.038), and a trend for improved peak post-ischemic blood flow in the leg was found (+17%, p = 0.079). Liver function improved: compared with placebo, levels of gamma-glutamyl transferase, aspartate transaminase, and soluble tumor necrosis factor alpha receptor 1 were lower after treatment with UDCA than after placebo (all p < 0.05). There was no change in 6-min walk test or New York Heart Association functional class, and levels of tumor necrosis factor alpha and interleukin-6 were unchanged or increased compared with placebo. CONCLUSIONS: UDCA is well tolerated in patients with CHF. UDCA improves peripheral blood flow and is associated with improved markers of liver function. PMID- 22300694 TI - Bile salts for the treatment of heart failure: out on a limb for a gut feeling? PMID- 22300695 TI - Atrial conduction slows immediately before the onset of human atrial fibrillation: a bi-atrial contact mapping study of transitions to atrial fibrillation. AB - OBJECTIVES: The aim of this study was to determine whether onset sites of human atrial fibrillation (AF) exhibit conduction slowing, reduced amplitude, and/or prolonged duration of signals (i.e., fractionation) immediately before AF onset. BACKGROUND: Few studies have identified functional determinants of AF initiation. Because conduction slowing is required for reentry, we hypothesized that AF from pulmonary vein triggers might initiate at sites exhibiting rate-dependent slowing in conduction velocity (CV restitution) or local slowing evidenced by signal fractionation. METHODS: In 28 patients with AF (left atrial size 43 +/- 5 mm; n = 13 persistent) and 3 control subjects (no AF) at electrophysiological study, we measured bi-atrial conduction time (CT) electrogram fractionation at 64 or 128 electrodes with baskets in left (n = 17) or both (n = 14) atria during superior pulmonary vein pacing at cycle lengths (CL) accelerating from 500 ms (120 beats/min) to AF onset. RESULTS: Atrial fibrillation initiated in 19 of 28 AF patients and no control subjects. During rate acceleration, conduction slowed in 23 of 28 AF patients (vs. no control subjects, p = 0.01) at the site of AF initiation (15 of 19) or latest activated site (20 of 28). The CT lengthened from 79 +/- 23 ms to 107 +/- 39 ms (p < 0.001) on acceleration, in a spectrum from persistent AF (greatest slowing) to control subjects (least slowing; p < 0.05). Three patterns of CV restitution were observed: 1) broad (gradual CT prolongation, 37% patients); 2) steep (abrupt prolongation, at CL 266 +/- 62 ms, 42%); and 3) flat (no prolongation, 21% AF patients, all control subjects). The AF initiation was more prevalent in patients with CV restitution (17 of 23 vs. 2 of 8; p = 0.03) and immediately followed abrupt re-orientation of the activation vector in patients with broad but not steep CV restitution (p < 0.01). Patients with broad CV restitution had larger atria (p = 0.03) and were more likely to have persistent AF (p = 0.04). Notably, neither amplitude nor duration (fractionation) of the atrial signal at the AF initiation site were rate dependent (both p = NS). CONCLUSIONS: Acceleration-dependent slowing of atrial conduction (CV restitution) precedes AF initiation, whereas absence of CV restitution identifies inability to induce AF. Conduction restitution, but not fractionated electrograms, may thus track the functional milieu enabling AF initiation and has implications for guiding AF ablation and pharmacological therapy. PMID- 22300696 TI - Incidence of and risk factors for sudden cardiac death in children with dilated cardiomyopathy: a report from the Pediatric Cardiomyopathy Registry. AB - OBJECTIVES: The purpose of this study was to establish the incidence of and risk factors for sudden cardiac death (SCD) in pediatric dilated cardiomyopathy (DCM). BACKGROUND: The incidence of SCD in children with DCM is unknown. The ability to predict patients at high risk of SCD will help to define who may benefit most from implantable cardioverter-defibrillators. METHODS: The cohort was 1,803 children in the PCMR (Pediatric Cardiomyopathy Registry) with a diagnosis of DCM from 1990 to 2009. Cumulative incidence competing-risks event rates were estimated. We achieved risk stratification using Classification and Regression Tree methodology. RESULTS: The 5-year incidence rates were 29% for heart transplantation, 12.1% non-SCD, 4.0% death from unknown cause, and 2.4% for SCD. Of 280 deaths, 35 were SCD, and the cause was unknown for 56. The 5-year incidence rate for SCD incorporating a subset of the unknown deaths is 3%. Patients receiving antiarrhythmic medication were at higher risk of SCD (hazard ratio: 3.0, 95% confidence interval: 1.1 to 8.3, p = 0.025). A risk stratification model based on most recent echocardiographic values had 86% sensitivity and 57% specificity. Thirty of 35 SCDs occurred in patients who met all these criteria: left ventricular (LV) end-systolic dimension z-score >2.6, age at diagnosis younger than 14.3 years, and the LV posterior wall thickness to end-diastolic dimension ratio <0.14. Sex, ethnicity, cause of DCM, and family history were not associated with SCD. CONCLUSIONS: The 5-year incidence rate of SCD in children with DCM is 3%. A risk stratification rule (86% sensitivity) included age at diagnosis younger than 14.3 years, LV dilation, and LV posterior wall thinning. Patients who consistently meet these criteria should be considered for implantable cardioverter-defibrillator placement. PMID- 22300697 TI - In vivo detection of oxidation-specific epitopes in atherosclerotic lesions using biocompatible manganese molecular magnetic imaging probes. AB - OBJECTIVES: This study sought to evaluate the in vivo magnetic resonance imaging (MRI) efficacy of manganese [Mn(II)] molecular imaging probes targeted to oxidation-specific epitopes (OSE). BACKGROUND: OSE are critical in the initiation, progression, and destabilization of atherosclerotic plaques. Gadolinium [Gd(III)]-based MRI agents can be associated with systemic toxicity. Mn is an endogenous, biocompatible, paramagnetic metal ion that has poor MR efficacy when chelated, but strong efficacy when released within cells. METHODS: Multimodal Mn micelles were generated to contain rhodamine for confocal microscopy and conjugated with either the murine monoclonal IgG antibody MDA2 targeted to malondialdehyde (MDA)-lysine epitopes or the human single-chain Fv antibody fragment IK17 targeted to MDA-like epitopes ("targeted micelles"). Micelle formulations were characterized in vitro and in vivo, and their MR efficacy (9.4-T) evaluated in apolipoprotein-deficient (apoE(-/-)) and low density lipoprotein receptor negative (LDLR(-/-)) mice (0.05 mmol Mn/kg dose) (total of 120 mice for all experiments). In vivo competitive inhibition studies were performed to evaluate target specificity. Untargeted, MDA2-Gd, and IK17-Gd micelles (0.075 mmol Gd/kg) were included as controls. RESULTS: In vitro studies demonstrated that targeted Mn micelles accumulate in macrophages when pre-exposed to MDA-LDL with ~10* increase in longitudinal relativity. Following intravenous injection, strong MR signal enhancement was observed 48 to 72 h after administration of targeted Mn micelles, with colocalization within intraplaque macrophages. Co-injection of free MDA2 with the MDA2-Mn micelles resulted in full suppression of MR signal in the arterial wall, confirming target specificity. Similar MR efficacy was noted in apoE(-/-) and LDLR(-/-) mice with aortic atherosclerosis. No significant differences in MR efficacy were noted between targeted Mn and Gd micelles. CONCLUSIONS: This study demonstrates that biocompatible multimodal Mn-based molecular imaging probes detect OSE within atherosclerotic plaques and may facilitate clinical translation of noninvasive imaging of human atherosclerosis. PMID- 22300698 TI - Stent in the heart. PMID- 22300699 TI - President's page: a transformational troika. PMID- 22300700 TI - Differences in treatment patterns and outcomes between Hispanics and non-Hispanic Whites treated for ST-segment elevation myocardial infarction: results from the NCDR ACTION Registry-GWTG. PMID- 22300701 TI - Intracardiac electrogram and ischemia alert. PMID- 22300702 TI - Thrombotic obstruction of mechanical prosthetic valve in mitral position the old "x-ray" fights the new 3-dimensional transesophageal echocardiography. PMID- 22300703 TI - A meta-analysis of male breast cancer in Africa. AB - To characterize male breast cancer in Africa in recent decades, we systematically reviewed literature and conducted a meta-analysis of available data on male breast cancer in Africa. A paper was included if both male and female breast cancer were available. If two publications covered the same geographic area, only the publication with a longer study period was included. Random effects models and mixed effect meta-regressions were used to analyze data of 1201 male and 36,172 female breast cancer patients from 27 African countries. We showed that the male-to-female breast cancer ratio was 0.042 overall and it has decreased in recent years. Additionally, male breast cancer patients in Africa had the disease at age 54.6 on average, 7 years older than female patients. In conclusion, male breast cancers in Africa are characterized as late onset and male-to-female breast cancer ratio in Africa is higher than populations in developed countries. PMID- 22300704 TI - Angiogenesis and expression of vascular endothelial growth factor, tumour necrosis factor-alpha and hypoxia inducible factor-1alpha in canine renal cell carcinoma. AB - The aim of the present study was to determine the distribution and characteristics of microvessels in various histological types of canine renal cell carcinoma (RCC). The study compared microvessel density (MVD) and distribution of blood vessels according to histological type and evaluated the presence of angiogenesis-related proteins. Nine archival samples of canine RCC were studied. MVD was calculated as the mean number of blood vessels per mm(2). The diameter of blood vessels was calculated by determining either the length of the long axis of blood vessels (diameter(max)) or the mean distance from the centre of each blood vessel to the tunica adventia (diameter(mean)). A significant difference in MVD was evident between RCCs and normal kidneys (46.6 +/- 28.0 versus 8.4 +/- 2.2 microvessels/mm(2)). Diameter(max) in canine RCCs (34.1 +/- 14.7 MUm) was also significantly different from normal canine kidney (23.2 +/- 3.4 MUm). Vascular endothelial growth factor (VEGF) was expressed by tumour cells and vascular endothelial cells and tumour necrosis factor (TNF) alpha expression was observed in vascular endothelial cells in both neoplastic and normal kidney. Although VEGF is involved in angiogenesis and correlates with tumour stage of development, no correlation was found between VEGF expression and MVD. Tumour-associated macrophages expressing TNF-alpha and hypoxia inducible factor 1alpha were identified in peritumoural tissue and may play an important role in angiogenesis. PMID- 22300705 TI - Histological subtypes of oral non-tonsillar squamous cell carcinoma in dogs. AB - Several histological subtypes and grades of oral squamous cell carcinoma (SCC) are described in human literature and these subtypes have distinct morphological features and biological behaviour. This retrospective study (1990-2010) included 84 dogs diagnosed with SCC of the oral cavity and oropharynx, excluding the tonsils. Sixty-nine of the SCCs (82.1%) were further diagnosed as conventional SCC (CSCC) (33 [47.8%] well-differentiated, 31 [44.9%] moderately-differentiated and five [7.3%] poorly-differentiated), five (5.95%) each as papillary SCC and basaloid SCC, three (3.6%) as adenosquamous carcinoma and two (2.4%) as spindle cell carcinoma. Compared with the general hospital population, neutered female dogs, dogs aged 10 to <15 years, English springer spaniels and Shetland sheepdogs were overrepresented. The majority (78.1%) of SCCs were proliferative with or without associated ulceration, although no significant association was observed between the gross appearance and different SCC subtypes. 71.4% of SCCs were located in dentate jaws; however, well-differentiated CSCC more often affected the tongue and other non-dentate mucosal surfaces (P=0.0022). No significant association was found between any of the SCC subtypes and tumour-associated inflammation (TAI), perineural and lymphovascular invasion (PNI, LVI), or between gross appearance of the tumour and tumour location, PNI, LVI or TAI or PNI, LVI, TAI and tumour location. PMID- 22300706 TI - Mucocutaneous candidiasis in a mandrill (Mandrillus sphinx). AB - An adult male mandrill (Mandrillus sphinx) suffered from chronic ulceration of the facial and gluteal skin and the oral and nasal mucosa. The ulcers were resistant to therapy and led to deterioration in the general condition of the animal. Microscopical examination revealed a severe, chronic, multifocal, granulomatous and eosinophilic dermatitis and panniculitis. There was also stomatitis and rhinitis with numerous intralesional fungal elements. These organisms were identified by immunohistochemistry, transmission electron microscopy, polymerase chain reaction and fungal culture as Candida albicans. Species identification was confirmed by MALDI-TOF mass spectrometry. A specific predisposing immunosuppressive factor for the deep chronic mucocutaneous candidiasis was not identified; however, social stress and/or a primary defect in cell-mediated immunity could not be excluded as possible causes for a predisposing immunodeficiency in the animal. PMID- 22300707 TI - Imatinib mesylate prevents cerebral vasospasm after subarachnoid hemorrhage via inhibiting tenascin-C expression in rats. AB - Platelet-derived growth factor (PDGF) has been implicated in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH), but the mechanism remains unknown. The purpose of this study was to assess whether imatinib mesylate (imatinib), an inhibitor of the tyrosine kinases of PDGF receptors (PDGFRs), prevents cerebral vasospasm after SAH in rats, and to elucidate if tenascin-C (TNC), a matricellular protein, is involved in the mechanism. Imatinib (10 or 50 mg/kg body weight) was administered intraperitoneally to rats undergoing SAH by endovascular perforation, and the effects were evaluated by neurobehavioral tests and India-ink angiography at 24-72 h post-SAH. Western blotting and immunohistochemistry were performed to explore the underlying mechanisms in cerebral arteries at 24h post-SAH. Recombinant TNC was administered intracisternally to imatinib-treated SAH rats, and the effects were evaluated by neurobehavioral tests, India-ink angiography and immunohistochemistry at 24 h post-SAH. Both dosages of imatinib significantly prevented post-SAH neurological impairments and vasospasm at 24-72 h. SAH caused PDGFR-beta upregulation, PDGFR activation, mitogen-activated protein kinase activation, and TNC upregulation in the spastic cerebral arteries, all of which were significantly suppressed by imatinib treatment. Recombinant TNC reversed the anti-vasospastic effects and protein expression changes by imatinib. This study suggests that imatinib prevents cerebral vasospasm at least partly via inhibiting the upregulation of TNC, implying that TNC may be a new therapeutic target for post-SAH vasospasm. PMID- 22300708 TI - Fibroblast growth factors preserve blood-brain barrier integrity through RhoA inhibition after intracerebral hemorrhage in mice. AB - Fibroblast growth factors (FGFs) maintain and promote vascular integrity; however whether FGFs protect the blood-brain barrier (BBB) after intracerebral hemorrhage (ICH) remains unexplored. In this present study, we hypothesized that exogenous FGF administration attenuates brain injury after ICH, specifically by preserving endothelial adherens junctions, therefore reducing vasogenic brain edema and attenuating neurofunctional deficits in mice subjected to experimental ICH. Acid fibroblast growth factor (FGF1) or basic fibroblast growth factor (FGF2) was administered intracerebroventricularly (ICV) at 0.5 h after intrastriatal injection of bacterial collagenase (cICH) or autologous whole blood (bICH). Fibroblast growth factor receptor (FGFR) inhibitor PD173074 and phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 were additionally administered with FGF2. The selective Rho-associated coiled-coil forming protein serine/threonine kinase (ROCK) inhibitor Y27632 was independently administered at 0.5 h after cICH. Brain water content and neurofunctional deficits were evaluated at 24 and 72h after ICH induction. Evans blue extravasation as well as Western blot analysis for the quantification of activated FGFR, Akt, Ras-related C3 botulinum toxin substrate 1 (Rac1), Ras homolog gene family member A (RhoA) and adherens junction proteins (p120-catenin, beta-catenin and VE-cadherin) were conducted at 72 h post-cICH. FGF treatment reduced perihematomal brain edema and improved neurofunctional deficits at 72 h after experimental ICH (p<0.05, compared to vehicle); however, FGFR and PI3K inhibition reversed these neuroprotective effects. Exogenous FGF2 increased activated FGFR, Akt, and Rac1 but reduced activated RhoA protein expression at 72 h after cICH (p<0.05, compared to vehicle), which was reversed by FGFR and PI3K inhibition. Y27632 treatment reduced brain injury at 72 h after cICH (p<0.05, compared to vehicle) and increased the expression of catenins (p120-catenin, beta-catenin). In conclusion, our findings suggest that exogenous FGF treatment reduced RhoA activity via FGFR-induced activation of the PI3K-Akt-Rac1 signaling pathway, thus preserving BBB integrity, and therefore attenuating secondary brain injury after experimental ICH in mice. PMID- 22300709 TI - Quantitative trait loci on chromosome 1 for cataract and AMD-like retinopathy in senescence-accelerated OXYS rats. AB - Age-related macular degeneration (AMD) and cataract are common age-related diseases in humans. Previously we showed that senescence-accelerated OXYS rats develop retinopathy and cataract, which are comparable to human AMD and senile cataract. Here we focused on the identification of quantitative trait loci (QTLs), which affect early-onset cataract and retinopathy in OXYS rats, using F2 hybrids bred by a reciprocal cross (OXYS*WAG and WAG*OXYS). Chromosome 1 showed significant associations between retinopathy and loci in the regions of markers D1Rat30 and D1Rat219 (QTL1) as well as D1Rat219 and D1Rat81 (QTL2); and between early cataract development with the locus in the region of the markers D1Rat219 and D1Rat81 (QTL2). To determine the effects of these QTLs, we generated two congenic strains by transferring chromosome 1 regions from OXYS into WAG background. Both congenic strains (named WAG/OXYS-1.1 and WAG/OXYS-1.2, respectively) display early cataract and retinopathy development. Thus, we confirmed that genes located in the analyzed regions of chromosome 1 are associated with the development of these diseases in OXYS rats. PMID- 22300710 TI - Concurrent impairments in sleep and memory in amnestic mild cognitive impairment. AB - Whereas patients with Alzheimer's disease (AD) experience difficulties forming and retrieving memories, their memory impairments may also partially reflect an unrecognized dysfunction in sleep-dependent consolidation that normally stabilizes declarative memory storage across cortical areas. Patients with amnestic mild cognitive impairment (aMCI) exhibit circumscribed declarative memory deficits, and many eventually progress to an AD diagnosis. Whether sleep is disrupted in aMCI and whether sleep disruptions contribute to memory impairment is unknown. We measured sleep physiology and memory for two nights and found that aMCI patients had fewer stage-2 spindles than age-matched healthy adults. Furthermore, aMCI patients spent less time in slow-wave sleep and showed lower delta and theta power during sleep compared to controls. Slow-wave and theta activity during sleep appear to reflect important aspects of memory processing, as evening-to-morning change in declarative memory correlated with delta and theta power during intervening sleep in both groups. These results suggest that sleep changes in aMCI patients contribute to memory impairments by interfering with sleep-dependent memory consolidation. PMID- 22300711 TI - Long term respiratory outcomes of very premature birth (<32 weeks). AB - Many very prematurely born infants develop bronchopulmonary dysplasia (BPD), remaining oxygen dependent for many months and requiring frequent rehospitalisations. Troublesome, recurrent respiratory symptoms requiring treatment and lung function abnormalities at follow-up are common. The most severely affected may remain symptomatic with evidence of airways obstruction even as adults. Data from adolescents and adults on the respiratory outcome of extreme prematurity, however, are usually from patients who have had 'classical' BPD with severe respiratory failure in the neonatal period. Nowadays, infants have 'new' BPD developing chronic oxygen dependence despite initially minimal or even no respiratory distress. Affected patients do suffer chronic respiratory morbidity and their lung function may deteriorate during the first year after birth. Infants who suffer respiratory syncytial virus lower respiratory tract infections are most likely to require rehospitalisation and suffer chronic respiratory morbidity, but this may reflect greater abnormal premorbid lung function. PMID- 22300712 TI - Sex steroids in Sjogren's syndrome. AB - The purpose of the review is to consider pathomechanisms of Sjogren's syndrome (SS), which could explain the female dominance (9:1), the most common age of onset (40-50 years) and targeting of the exocrine glands. Estrogens seem to specifically protect secretory glandular acinar cells against apoptosis whereas lack of estrogens during menopause and climacterium specifically leads to increased apoptosis of the exocrine secretory cells. Male gonads produce testosterone and convert it in exocrine glands to dihydrotesterosterone (DHT), which is anti-apoptotic and protects against acinar cell apoptosis. Estrogen deficient women need to produce dehydroepiandrosterone (DHEA) in the adrenal glands and convert it to DHT in exocrine glands in a complex and branching reaction network in which individual enzymatic reactions are catalyzed in forward and backward directions by a myriad of different isoforms of steroidogenic enzymes. Tailoring DHT in peripheral tissues is much more complex and vulnerable in women than in men. In SS the intracrine steroidogenic enzyme machinery is deranged. These endo-/intracrine changes impair acinar remodeling due to impaired integrin alpha1beta1 and integrin alpha2beta1 expression so that the intercalated duct progenitor cells are unable to migrate to the acinar space, to differentiate to secretory acinar cells upon contact with laminin-111 and laminin-211 specifically found in the acinar basement membrane. The disarranged endo /intracrine estrogen/androgen balance induces acinar cells to release microparticles and apoptotic bodies and to undergo apoptotis and/or anoikis. Membrane particles contain potential autoantigens recognized by T- (TCRs) and B cell receptors (BCRs) and danger-associated molecular patterns (DAMPs) recognized by Toll-like receptors (TLRs). In membrane particles (or carrier-complexes) antigen/adjuvant complexes could stimulate professional antigen capturing, processing and presenting cells, which can initiate auto-inflammatory and autoimmune cascades, break the self-tolerance and finally lead to SS. PMID- 22300713 TI - Socioeconomic pathways to depressive symptoms in adulthood: evidence from the National Longitudinal Survey of Youth 1979. AB - The existence of a direct effect of early socioeconomic position (SEP) on adult mental health outcomes net of adult SEP is still debated. This question demands the explicit modeling of pathways linking early SEP to adult SEP and mental health. In light of this background, we pursue two objectives in this study. First, we examine whether depressive symptoms in adulthood can be fit in a trajectory featuring both an intercept, or baseline range of depressive symptoms that varied between individuals, and a slope describing the average evolution of depressive symptoms over the years. Second, we estimate the direct and indirect pathways linking early SEP, respondents' education and adult household income, with a particular focus on whether early SEP retains a significant direct effect on the trajectory of depressive symptoms once adult SEP is entered into the pathway model. Drawing from 29 years of cohort data from the National Longitudinal Survey of Youth 1979, a survey that has been following a national probability sample of American civilian and military youth (Zagorsky and White, 1999), we used structural equation models to estimate the pathways between parents' education, respondent's education, and latent growth curves of household income and depressive symptoms. We found that the effect of parents' education was entirely mediated by respondent's education. In turn, the effect of respondent's education was largely mediated by household income. In conclusion, our findings showed that the socioeconomic attainment process that is rooted in parents' education and leads to respondent's education and then to household income is a crucial pathway for adult mental health. These results suggest that increasing educational opportunities may be an effective policy to break the intergenerational transmission of low socioeconomic status and poor mental health. PMID- 22300714 TI - Uses and abuses of the resilience construct: loss, trauma, and health-related adversities. PMID- 22300715 TI - Attachment style contributes to the outcome of a multimodal lifestyle intervention. AB - BACKGROUND & AIMS: The long-term success of life-style interventions in the treatment of obesity is limited. Although psychological factors have been suggested to modify therapeutic effects, specifically the implications of attachment styles and the patient-therapist relationship have not been examined in detail yet. METHODS: This study included 44 obese patients who participated in a one-year multimodal weight-reduction program. Attachment style was analyzed by the Adult Attachment Prototype Rating (AAPR) inventory and its relation to a one year weight reduction program was studied. The patient-therapist-relationship was assessed using the Helping Alliance Questionnaire. RESULTS: Attachment style was secure in 68% of participants and insecure (preoccupied and dismissing) in 32%. Interestingly a significantly higher weight-reduction was found in securely (SAI) compared to insecurely attached individuals (UAI; p < 0.05). This estimation correlated positively also to the quality of helping alliance (p = 0.004). CONCLUSIONS: The frequency of insecure attachment in obese individuals was comparable to that of the normal population. Our data suggest a greater weight reduction for SAI than for UAI, and the patient-therapist relationship was rated more positively. The conclusion can be drawn that a patient's attachment style plays a role in an interdisciplinary treatment program for obesity and has an influence on the effort to lose weight. PMID- 22300716 TI - Isolation of a novel alkaline-induced laccase from Flammulina velutipes and its application for hair coloring. AB - Laccase is a member of the multi-copper oxidase family and a promising for hair coloring. In this study, we isolated a novel alkaline-induced laccase from the white-rot fungus Flammulina velutipes and studied the possibility to apply the enzyme for hair coloring. Laccase activity detected in the culture supernatant of F. velutipes was found to significantly increase when exchanging the medium to laccase inducing one whose pH was adjusted to 9.0. Three isozymes were detected by activity staining on non-denaturing SDS-PAGE. The major isozyme, Flac1, was purified from the culture supernatant after being induced at pH 9.0 by ion exchange column chromatography. The N-terminal peptide sequence of Flac1 was determined, revealing clear homology with laccases from other white-rot fungi. Optimum pH of oxidation was found to be around pH 5.0-6.5 regardless of several different substrates used. Oxidation activities of Flac1 to several hair dye agents as substrate showed the higher activity at pH 6.5 than that at pH 9.0. Oxidation activity was also detected at pH 9.0 which was suitable for hair coloring. When the purified Flac1 was applied for hair coloring system without using hydrogen peroxide, effective coloring was observed at the protein amount of 0.25mg/1g of hair used. These results indicated that this alkaline-induced novel laccase isolated from the culture supernatant of F. velutipes might be a useful enzyme for hair color. PMID- 22300717 TI - Isolation process of industrially useful Clostridium bifermentans from natural samples. AB - A selective isolation procedure of clostridial strains from natural samples able to convert glycerol to 1,3-propanediol (1,3-PD) and organic acids was investigated. The modified PY medium of high concentration of NaHCO(3) was shown to be highly selective for Clostridium bifermentans. Obtained isolates produced mainly 1,3-PD, lactic, acetic, and formic acids from glycerol. PMID- 22300718 TI - The influence of BCG vaccine strain on mycobacteria-specific and non-specific immune responses in a prospective cohort of infants in Uganda. AB - BACKGROUND: Globally, BCG vaccination varies in efficacy and has some non specific protective effects. Previous studies comparing BCG strains have been small-scale, with few or no immunological outcomes and have compared TB-specific responses only. We aimed to evaluate both specific and non-specific immune responses to different strains of BCG within a large infant cohort and to evaluate further the relationship between BCG strain, scarring and cytokine responses. METHODS: Infants from the Entebbe Mother and Baby Study (ISRCTN32849447) who received BCG-Russia, BCG-Bulgaria or BCG-Denmark at birth, were analysed by BCG strain group. At one year, interferon-gamma (IFN-gamma), interleukin (IL)-5, IL-13 and IL-10 responses to mycobacteria-specific antigens (crude culture filtrate proteins and antigen 85) and non-mycobacterial stimuli (tetanus toxoid and phytohaemagglutinin) were measured using ELISA. Cytokine responses, scar frequency, BCG associated adverse event frequency and mortality rates were compared across groups, with adjustments for potential confounders. RESULTS: Both specific and non-specific IFN-gamma, IL-13 and IL-10 responses in 1341 infants differed between BCG strain groups including in response to stimulation with tetanus toxoid. BCG-Denmark immunised infants showed the highest cytokine responses. The proportion of infants who scarred differed significantly, with BCG scars occurring in 52.2%, 64.1% and 92.6% of infants immunised with BCG Russia, BCG-Bulgaria and BCG-Denmark, respectively (p<0.001). Scarred infants had higher IFN-gamma and IL-13 responses to mycobacterial antigens only than infants without a scar. The BCG-Denmark group had the highest frequency of adverse events (p=0.025). Mortality differences were not significant. CONCLUSIONS: Both specific and non-specific immune responses to the BCG vaccine differ by strain. Scarring after BCG vaccination is also strain-dependent and is associated with higher IFN gamma and IL-13 responses to mycobacterial antigens. The choice of BCG strain may be an important factor and should be evaluated when testing novel vaccine strategies that employ BCG in prime-boost sequences, or as a vector for other vaccine antigens. PMID- 22300719 TI - Knowledge, attitude and practice in primary and secondary cervical cancer prevention among young adult Italian women. AB - In Italy since 2007 vaccination against human papillomavirus (HPV) is offered to 11-year-old females, whereas vaccination for older age groups is still a matter of debate. To assess Italian young women's knowledge, attitudes and practice regarding primary and secondary cervical cancer prevention a cross-sectional study among young women aged 18-26 years was conducted in 2008. The survey collected information on in-depth awareness and knowledge regarding Pap testing, HPV infection, HPV vaccine and cervical cancer. The response rate was 57.7% with a wide range of variability (34-84%) amongst local health units. Among 667 women who participated in the survey poor awareness and various misconceptions regarding HPV and cervical cancer prevention were detected. Overall women were found to be more knowledgeable about Pap smears and cervical cancer than about HPV infection and the HPV vaccine. Respondents pointed to their healthcare providers as their most trusted source for medical information. Understanding women's knowledge on cervical cancer prevention, as well as related factors is important in helping to achieve and maintain adherence to cervical cancer preventive strategies. Moreover in order to minimize cervical cancer risk by improving women's adherence to preventive strategies, appropriate and adequate information dissemination, and guidance from health professionals appear to be crucial elements. PMID- 22300720 TI - Is the pneumococcal vaccine Advance Market Commitment motivating innovation and increasing manufacturing capacity? Some preliminary answers. AB - This paper seeks to give some preliminary evidence on the potential outcome of the pneumococcal vaccine Advance Market Commitment (AMC), with a focus on its impact on innovation in 'emerging' vaccine manufacturers in developing countries. The evidence is derived from a series of interviews with executives at industrial vaccine developing organizations with pneumococcal vaccines in their R&D portfolio, including both multinational pharmaceutical companies and 'emerging' manufacturers. The main findings are that so far there is no evidence to support any claim that the AMC is speeding innovation of pneumococcal vaccines, or that it is contributing to productive capacity expansion. Representatives of emerging manufacturers consistently state that the AMC is either irrelevant or inappropriate for supporting their innovative activities on pneumococcal vaccines. PMID- 22300721 TI - Barriers to and facilitators of child influenza vaccine - perspectives from parents, teens, marketing and healthcare professionals. AB - BACKGROUND: The CDC recommends annual influenza vaccination for all children age 6 months and older, yet vaccination rates remain modest. Effective strategies to improve influenza vaccination for children are needed. METHODS: Eight focus groups with 91 parents, teens, pediatric healthcare staff and providers, and immunization and marketing experts were conducted, audiotaped, transcribed verbatim, and coded based on grounded theory. RESULTS: Three themes emerged: barriers, facilitators, and strategies. Barriers included fear, misinformation, and mistrust, with exacerbation of these barriers attributed to media messages. Many considered influenza vaccination unnecessary and inconvenient, but would accept vaccination if recipients or other family members were considered high risk, if recommended by their doctor or another trusted person, or if offered or mandated by the school. Access to better information regarding influenza disease burden and vaccine safety and efficacy were notable facilitators, as were prevention of the inconvenience of missing work or important events, and if the child requests to receive the vaccine. Marketing strategies included incentives, jingles, videos, wearable items, strategically-located information sheets or posters, and promotion by informed counselors. Practice-based strategies included staff buy-in, standing orders protocols, vaccination clinics, and educational videos. Teen-specific strategies included message delivery through schools, texting, internet, and social networking sites. CONCLUSION: To improve influenza vaccination rates for children using practice-based interventions, participants suggested campaigns that provide better information regarding the vaccine, the disease and its implications, and convenient access to vaccination. Strategies targeting adolescents should use web-based social marketing technologies and campaigns based in schools. PMID- 22300722 TI - Immunogenicity study of plant-made oral subunit vaccine against porcine reproductive and respiratory syndrome virus (PRRSV). AB - Currently, killed-virus and modified-live PRRSV vaccines are used to control porcine reproductive and respiratory syndrome disease (PRRS). However, very limited efficacy of killed-virus vaccines and serious safety concerns for modified-live virus vaccines demand the development of novel PRRSV vaccines. In this report, we investigated the possibility of using transgenic plants as a cost effective and scalable system for production and delivery of a viral protein as an oral subunit vaccine against PRRSV. Corn calli were genetically engineered to produce PRRSV viral envelope-associated M protein. Both serum and intestine mucosal antigen-specific antibodies were induced by oral administration of the transgenic plant tissues to mice. In addition, serum and mucosal antibodies showed virus neutralization activity. The neutralization antibody titers after the final boost reached 6.7 in serum and 3.7 in fecal extracts, respectively. A PRRSV-specific IFN-gamma response was also detected in splenocytes of vaccinated animals. These results demonstrate that transgenic corn plants are an efficient subunit vaccine production and oral delivery system for generation of both systemic and mucosal immune responses against PRRSV. PMID- 22300723 TI - Yeast expressed classical swine fever E2 subunit vaccine candidate provides complete protection against lethal challenge infection and prevents horizontal virus transmission. AB - Classical swine fever (CSF) caused by the classical swine fever virus (CSFV) is a highly contagious swine disease resulting in large economical losses worldwide. The viral envelope glycoprotein E(rns) and E2 are major targets for eliciting antibodies against CSFV in infected animals. A Pichia pastoris yeast expressed E2 protein (yE2) has been shown to induce a protective immune response against CSFV challenge. The purpose of this study is to determine the optimal dose of yE2 and its efficacy on the prevention of virus horizontal transmission. A yeast expressed E(rns) (yE(rns)) protein was also included to evaluate its immunogenicity. The yE(rns) vaccinated pigs seroconverted to CSFV-E(rns)-specific antibody but no neutralizing antibody was detected and none survived after challenge infection, suggesting yE(rns) and yE2 retain correct immunogenicity but only the yE2 is able to induce a protective immune response. All three doses of yE2 (200, 300, and 400MUg) could elicit high titers of neutralizing antibodies and protective responses after challenge. The yE2/200 group demonstrated a mild fever response but recovered soon, and none of the yE2/300 and yE2/400 pigs became febrile. The optimal dose of yE2 was recommended to be 300MUg of the total amount of secreted proteins. In addition, the yE2 vaccine could cross-protect from all three genotypes of viruses. Further, the yE2 vaccine efficacy in preventing virus horizontal transmission was evaluated by cohabitation of unimmunized sentinels 3 days after challenge infection. All the sentinel pigs were alive and had no clinical symptoms confirming yE2 vaccine could confer a protective immune response and prevent horizontal transmission of CSFV. PMID- 22300724 TI - Vaccination of chickens with Salmonella Pathogenicity Island (SPI) 1 and SPI2 defective mutants of Salmonella enterica serovar Enteritidis. AB - In this study we were interested in the vaccine potential of two attenuated mutants of Salmonella enterica serovar Enteritidis for poultry. The first mutant was attenuated by the removal of the whole Salmonella Pathogenicity Island 1 (SPI1) and the second mutant was devoid of the whole SPI2. These 2 mutants were used for oral vaccination of 2 chicken lines; Lohmann Brown and ISA Brown. Chickens were vaccinated orally on day 1 of life, revaccinated on day 21 and challenged on day 42. The challenge was performed either orally or intravenously. Despite a slightly different response between the two chicken lines, both the mutants gave protection to poultry against S. Enteritidis challenge as documented by findings such as the bacterial counts in tissues, spleen weight, antibody production and cytokine response (namely IL-17 and IL-22). When the 2 mutants were compared, vaccination with the SPI1 mutant proved to be more effective in the protection of poultry against S. Enteritidis challenge than the vaccination with the SPI2 mutant. On the other hand, vaccination with the SPI2 mutant stimulated a slightly higher antibody production and such a mutant might therefore be a better choice if Salmonella is used as a vector for the delivery of heterologous antigens with a desired stimulation of the humoral part of the immune system. PMID- 22300725 TI - Prospective epidemiologic surveillance of invasive pneumococcal disease and pneumonia in children in San Jose, Costa Rica. AB - BACKGROUND: Streptococcus pneumoniae (SP) is the leading cause of vaccine preventable death in children <5 years of age, globally. This surveillance determined incidence rates of invasive pneumococcal disease (IPD), clinical and chest radiograph-confirmed pneumonia (CXR+Pn); and SP serotype distribution and antimicrobial susceptibility in children in San Jose, Costa Rica. METHODS: This was a 2-year prospective, population-based surveillance conducted in 2007-2009 in children aged 28 days to 36 months presenting to participating healthcare centers. Eligibility criteria for study inclusion were as follows: temperature >= 39.0 degrees C within 24h and/or clinical suspicion of IPD or pneumonia. RESULTS: 8801 subjects were enrolled. Median age: 14.5 months. A total of 25 children had invasive pneumococcal disease with S. pneumoniae isolated from nonduplicative cultures (22) or detected solely by PCR and a clinical picture consistent with IPD (3). Sources of positive cultures (some children had >1 positive culture) were: blood (20), pleural fluid (4), and cerebrospinal fluid (3). Of the 3 cases detected solely by PCR, 2 were from cerebrospinal fluid and 1 from pleural fluid. The overall IPD incidence rates for culture-positive only cases for children aged 28 days to <3 years was 33.7/100,000 per year for years 1 and 2 combined. Age stratification of culture-positive only subjects showed a peak during year 1 (106.8/100,000) in children 28 days to <6 months of age group, and in year 2 (45.5/100,000) in children 12 months to <24 months of age group. Most common serotypes were 14 (28.6%), followed by 3, 4, 6A, 19A, and 22F (9.5% each). Of 22 nonduplicative IPD isolates, 42.9% were penicillin- and trimethoprim/sulfamethoxazole nonsusceptible isolates. Consideration of PCR positive cases increases the incidence of IPD for children aged 28 days to <3 years to 46.0/100,000. Overall incidence of clinical pneumonia and CXR+Pn was 1968/100,000 and 551/100,000, respectively. CONCLUSIONS: There is a considerable burden of IPD and pneumonia in children in San Jose. These epidemiologic data serve as a baseline to evaluate the effectiveness of the incorporation of new conjugate pneumococcal vaccines into the National Immunization Program in Costa Rican children. PMID- 22300726 TI - Attention-related modulation of auditory-cortex responses to speech sounds during dichotic listening. AB - Event-related magnetic fields (ERFs) were measured with magnetoencephalography (MEG) in fifteen healthy right-handed participants listening to sequences of consonant-vowel syllable pairs delivered dichotically (one syllable presented to the left ear and another syllable simultaneously to the right ear). The participants were instructed to press a response button to occurrences of a particular target syllable. In a condition with no other instruction (the non forced condition, NF), they showed the well-known right-ear advantage (REA), that is, the participants responded more often to target syllables delivered to the right ear than to targets delivered to the left ear. The same was true in the forced-right (FR) condition, where the participants were instructed to attend selectively to the right-ear syllables and respond only to targets among them. In the forced-left (FL) condition, where they were instructed to respond only to left-ear targets, they responded more often to targets in this ear than to targets in the right ear. At 300-500 ms from syllable pair onset, a sustained field (SF) in ERFs to the syllable pairs was stronger in the left auditory cortex than in the right auditory cortex in the NF and FR conditions, while the opposite was true in the FL condition. Thus selective attention during dichotic listening leads to stronger processing of speech sounds in the auditory cortex contralateral to the attended direction. Our results also suggest that the REA observed for dichotic speech may involve a bias of attention to the right side even when there is no instruction to do so. This supports Kinsbourne's (1970) model of attention bias as a general principle of laterality. PMID- 22300727 TI - A new approach to the determination of concentration profiles in atom probe tomography. AB - Atom probe tomography (APT) provides three-dimensional analytical imaging of materials with near-atomic resolution using pulsed field evaporation. The processes of field evaporation can cause atoms to be placed at positions in the APT reconstruction that can deviate slightly from their original site in the material. Here, we describe and model one such process--that of preferential retention of solute atoms in multicomponent systems. Based on relative field evaporation probabilities, we calculate the point spread function for the solute atom distribution in the "z," or in-depth direction, and use this to extract more accurate solute concentration profiles. PMID- 22300728 TI - Gait symmetry and velocity differ in their relationship to age. AB - Measurement of gait is essential for identifying underlying deficits contributing to gait dysfunction, guiding clinical decisions and measuring rehabilitation outcomes. Velocity is commonly used to measure gait, however, its interpretation in patient populations is complicated by the confound of age. Gait symmetry may be an additional and valuable measure since it may not feature the same age related changes as velocity. The purpose of this study was to determine if gait symmetry is related to age. METHODS: Spatiotemporal gait parameters were recorded for 172 individuals with stroke and 81 healthy adults walking across a pressure sensitive mat at their preferred speed. Swing time, stance time and step length symmetry ratios were calculated. The relationship of age to velocity and symmetry was examined using Pearson correlations. RESULTS: There was a significant negative association between velocity and age in the healthy group (r=-0.57, p<0.01). There were no significant relationships between age and any of the three symmetry ratios for either the stroke or healthy groups. CONCLUSIONS: The main finding of the current study is that gait symmetry ratios are not significantly associated with age in either a healthy or a post-stroke group. Gait symmetry ratios may therefore, allow the clinician and the researcher to make judgments about the effects of disease (such as stroke) on the control of an individual's gait without the confound of age. PMID- 22300729 TI - The influence of heel height on lower extremity kinematics and leg muscle activity during gait in young and middle-aged women. AB - The aim of this study was to evaluate the changes in electromyographic (EMG) activity of the lower limb muscles, and hip, knee and ankle kinematics during gait while wearing low- (4-cm) and high-heeled (10-cm) shoes in 31 young and 15 middle-aged adult women. We observed an increase in knee flexion and decrease in ankle eversion associated with elevated heel heights suggesting that compensatory mechanisms attenuating ground reaction forces may be compromised during gait with higher-heeled shoes. Additionally, we observed increased muscle activity during high-heeled gait that may exacerbate muscle fatigue. Collectively, these findings suggest that permanent wearing of heeled footwear could contribute to muscle overuse and repetitive strain injuries. PMID- 22300730 TI - Ambulatory measurement of the scapulohumeral rhythm: intra- and inter-operator agreement of a protocol based on inertial and magnetic sensors. AB - To measure the scapulohumeral rhythm (SHR) in outpatient settings, the motion analysis protocol named ISEO (INAIL Shoulder and Elbow Outpatient protocol) was developed, based on inertial and magnetic sensors. To complete the sensor-to segment calibration, ISEO requires the involvement of an operator for sensor placement and for positioning the patient's arm in a predefined posture. Since this can affect the measure, this study aimed at quantifying ISEO intra- and inter-operator agreement. Forty subjects were considered, together with two operators, A and B. Three measurement sessions were completed for each subject: two by A and one by B. In each session, the humerus and scapula rotations were measured during sagittal and scapular plane elevation movements. ISEO intra- and inter-operator agreement were assessed by computing, between sessions, the: (1) similarity of the scapulohumeral patterns through the Coefficient of Multiple Correlation (CMC(2)), both considering and excluding the difference of the initial value of the scapula rotations between two sessions (inter-session offset); (2) 95% Smallest Detectable Difference (SDD(95)) in scapula range of motion. Results for CMC(2) showed that the intra- and inter-operator agreement is acceptable (median>=0.85, lower-whisker >= 0.75) for most of the scapula rotations, independently from the movement and the inter-session offset. The only exception is the agreement for scapula protraction-retraction and for scapula medio-lateral rotation during abduction (inter-operator), which is acceptable only if the inter-session offset is removed. SDD(95) values ranged from 4.4 degrees to 8.6 degrees for the inter-operator and between 4.9 degrees and 8.5 degrees for the intra-operator agreement. In conclusion, ISEO presents a high intra- and inter-operator agreement, particularly with the scapula inter-session offset removed. PMID- 22300731 TI - Automated method to distinguish toe walking strides from normal strides in the gait of idiopathic toe walking children from heel accelerometry data. AB - Toe walking mainly occurs in children due to medical condition or physical injury. When there are no obvious signs of any medical condition or physical injury, a diagnosis of Idiopathic Toe Walking (ITW) is made. ITW children habitually walk on their toes, however can modify their gait and walk with a heel toe gait if they want to. Correct gait assessment in ITW children therefore becomes difficult. To solve this problem, we have developed an automated way to assess the gait in ITW children using a dual axis accelerometer. Heel acceleration data was recorded from the gait of ITW children using boots embedded with the sensor in the heel and interfaced to a handheld oscilloscope. An innovative signal processing algorithm was developed in IgorPro to distinguish toe walking stride from normal stride using the acceleration data. The algorithm had an accuracy of 98.5%. Based on the statistical analysis of the heel accelerometer data, it can be concluded that the foot angle during mid stance in ITW children tested, varied from 36 degrees to 11.5 degrees while as in normal children the foot stance angle is approximately zero. This algorithm was later implemented in a system (embedded in the heel) which was used remotely to differentiate toe walking stride from normal stride. Although the algorithm classifies toe walking stride from normal stride in ITW children, it can be generalized for other applications such as toe walking in Cerebral Palsy or Acquired Brain Injury subjects. The system can also be used to assess the gait for other applications such as Parkinson's disease by modifying the algorithm. PMID- 22300732 TI - The secondary heart field is a new site of calcineurin/Nfatc1 signaling for semilunar valve development. AB - Semilunar valve malformations are common human congenital heart defects. Bicuspid aortic valves occur in 2-3% of the population, and pulmonic valve stenosis constitutes 10% of all congenital heart disease in adults (Brickner et al., 2000) [1]. Semilunar valve defects cause valve regurgitation, stenosis, or calcification, leading to endocarditis or congestive heart failure. These complications often require prolonged medical treatment or surgical intervention. Despite the medical importance of valve disease, the regulatory pathways governing semilunar valve development are not entirely clear. In this report we investigated the spatiotemporal role of calcineurin/Nfatc1 signaling in semilunar valve development. We generated conditional knockout mice with calcineurin gene disrupted in various tissues during semilunar valve development. Our studies showed that calcineurin/Nfatc1 pathway signals in the secondary heart field (SHF) but not in the outflow tract myocardium or neural crest cells to regulate semilunar valve morphogenesis. Without SHF calcineurin/Nfatc1 signaling, the conal endocardial cushions-the site of prospective semilunar valve formation- first develop and then regress due to apoptosis, resulting in a striking phenotype with complete absence of the aortic and pulmonic valves, severe valve regurgitation, and perinatal lethality. This role of calcineurin/Nfatc1 signaling in the SHF is different from the requirement of calcineurin/Nfatc1 in the endocardium for semilunar valve formation (Chang et al., 2004) [2], indicating that calcineurin/Nfatc1 signals in multiple tissues to organize semilunar valve development. Also, our studies suggest distinct mechanisms of calcineurin/Nfat signaling for semilunar and atrioventricular valve morphogenesis. Therefore, we demonstrate a novel developmental mechanism in which calcineurin signals through Nfatc1 in the secondary heart field to promote semilunar valve morphogenesis, revealing a new supportive role of the secondary heart field for semilunar valve formation. PMID- 22300733 TI - microRNAs in cardiovascular development. AB - Heart development requires precise temporal-spatial regulation of gene expression, in which the highly conserved modulation networks of transcription factors accurately control the signaling pathways required for normal cardiovascular development. Even slight perturbation of such programming during cardiogenesis can cause congenital heart defects and late neonatal or adult heart disease. microRNAs (miRNAs), a class of "small" non-coding RNAs, have recently drawn a lot of attention for their "big" impact on cardiovascular development and diseases. miRNAs negatively regulate the expression of their target genes in most biological organisms through post-transcriptional processes. Here, we review the roles of miRNAs in cardiovascular development and function, looking inside the molecular mechanisms by which miRNAs act as "fine tuners" and/or "safeguards" to maintain the homeostasis of cardiovascular system. We also propose new directions for therapeutic potential of these tiny molecules. PMID- 22300734 TI - Prevention of trinitrobenzene sulfonic acid-induced experimental colitis by oral administration of a poly(lactic-coglycolic acid) microsphere containing prostaglandin E2 receptor subtype 4 agonist. AB - Prostaglandin E2 receptor subtype 4 (EP4) agonists are known to reduce intestinal inflammation and enhance epithelium regeneration. We explored the possibility of colonic delivery of an EP4 agonist, 2-[(4-{[2-((1R,2R,3R)-3-hydroxy-2-{(1E,3S)-3 hydroxy-4-[3-(methoxymethyl)phenyl]but-1-enyl}-5 oxocyclopentyl)ethyl]sulfanyl}butanoyl)oxy]ethyl nonanoate (ONO-AE2-724), using poly(lactic-coglycolic acid) (PLGA) microspheres. Colitis was induced in mice by the intrarectal administration of trinitrobenzene sulfonic acid (TNBS). ONO-AE2 724-PLGA microspheres (EP4-MS) were prepared by the standard technique. Drug distributions after oral administration of EP4-MS were determined by liquid chromatography-tandem mass spectrometry analysis. To evaluate the protective effect of EP4-MS, animals were orally treated by gavage with single doses of EP4 MS 24 h before TNBS instillation. The changes in body weight, histopathology, immunohistochemistry, and expression of inflammatory cytokines were evaluated. Oral administration of EP4-MS enhanced colonic tissue drug concentration without any increase in the serum concentration during the 48 h after intake. EP4-MS pretreatment, but not unloaded ONO-AE2-724, significantly attenuated TNBS-induced colitis and diminished colonic mRNA expression levels of proinflammatory cytokines. In addition, a significant increase in the expression of CD25 and FoxP3 was found in isolated lamina propria CD4+ T cells of EP4-MS-treated mice. Immunohistochemical analysis of Ki-67 and single-stranded DNA revealed that EP4 MS pretreatment significantly suppressed apoptosis of colonic cells and promoted epithelial cell proliferation. These results suggest that EP4-MS protect mice from TNBS-induced colitis by intestinal local ONO-AE2-724 delivery. The EP4-MS may offer a promising new therapeutic strategy to treat inflammatory bowel diseases. PMID- 22300736 TI - Pediatric primary care services in Manitoba: is the health of the next generation of children at risk? AB - OBJECTIVES: Physician resource planning is an important part of health policy, but to date there are no studies measuring the primary care service needs of a particular population. The aim of this study was to project the expected provision of physician services for the pediatric population of one Canadian province for 2020. METHODS: A novel standardized measure of physician service provision, the equivalent services measure, was developed using mathematical modeling. Population projections and past use of services were used to calculate the projected service needs for the pediatric population of Manitoba. RESULTS: Despite projecting a small increase in the pediatric population (2.8%), our model predicted a decrease of 13.4% in the services that would be provided. CONCLUSIONS: The findings of this study indicate that the health of future generations of children may be at risk. Further research is needed to determine the effect of the reduction in pediatric service provision on the health of the pediatric population. PMID- 22300735 TI - Genetic predisposition factors and nasopharyngeal carcinoma risk: a review of epidemiological association studies, 2000-2011: Rosetta Stone for NPC: genetics, viral infection, and other environmental factors. AB - While infection with Epstein-Barr virus (EBV) is known to be an essential risk factor for the development of nasopharyngeal carcinoma (NPC), other co-factors including genetic factors are thought to play an important role. In this review, we summarize association studies conducted over the past decade to evaluate the role of genetic polymorphisms in NPC development. A review of the literature identified close to 100 studies, including 3 genome-wide association studies (GWAS), since 2000 that evaluated genetic polymorphisms and NPC risk in at least 100 NPC cases and 100 controls. Consistent evidence for associations were reported for a handful of genes, including immune-related HLA Class I genes, DNA repair gene RAD51L1, cell cycle control genes MDM2 and TP53, and cell adhesion/migration gene MMP2. However, for most of the genes evaluated, there was no effort to replicate findings and studies were largely modest in size, typically consisting of no more than a few hundred cases and controls. The small size of most studies, and the lack of attempts at replication have limited progress in understanding the genetics of NPC. Moving forward, if we are to advance our understanding of genetic factors involved in the development of NPC, and of the impact of gene-gene and gene-environment interations in the development of this disease, consortial efforts that pool across multiple, well designed and coordinated efforts will most likely be required. PMID- 22300737 TI - Association of hyperuricemia with renal outcomes, cardiovascular disease, and mortality. AB - BACKGROUND AND OBJECTIVES: Hyperuricemia is an independent risk factor for mortality, cardiovascular disease, and renal disease in general population. However, the relationship between hyperuricemia with clinical outcomes in CKD remains controversial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study investigated the association between uric acid with all-cause mortality, cardiovascular events, renal replacement therapy, and rapid renal progression (the slope of estimated GFR was less than -6 ml/min per 1.73 m(2)/y) in 3303 stages 3-5 CKD patients that were in the integrated CKD care system in one medical center and one regional hospital in southern Taiwan. RESULTS: In all subjects, the mean uric acid level was 7.9 +/- 2.0 mg/dl. During a median 2.8 year follow-up, there were 471 (14.3%) deaths, 545 (16.5%) cardiovascular events, 1080 (32.3%) participants commencing renal replacement therapy, and 841 (25.5%) participants with rapid renal progression. Hyperuricemia increased risks for all cause mortality and cardiovascular events (the adjusted hazard ratios for quartile four versus quartile one of uric acid [95% confidence interval] were 1.85 [1.40-2.44] and 1.42 [1.08-1.86], respectively) but not risks for renal replacement therapy (0.96 [0.79-1.16]) and rapid renal progression (1.30 [0.98 1.73]). CONCLUSIONS: In stages 3-5 CKD, hyperuricemia is a risk factor for all cause mortality and cardiovascular events but not renal replacement therapy and rapid renal progression. PMID- 22300738 TI - Interpretation of body mass index in children with CKD. AB - BACKGROUND AND OBJECTIVES: Clinical practice guidelines recommend that body mass index (BMI) in children with CKD be expressed relative to height-age (BMI-height age-z) rather than chronologic age (BMI-age-z) to account for delayed growth and sexual maturation. This approach has not been validated. This study sought to (1) compare children who have CKD with healthy children regarding the relationships between BMI-age-z and each of relative lean mass (LM) and adiposity and (2) determine whether BMI-height-age-z reflects relative LM and adiposity in CKD in the same way that BMI-age-z does in healthy children. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a cross-sectional study, dual-energy x-ray absorptiometry was used to assess whole-body fat mass (FM) and LM in 143 participants with CKD and 958 healthy participants (age, 5-21 years); FM and LM were expressed as sex-specific Z-scores relative to height (LM-height-z, FM height-z), with healthy participants as the reference. BMI-age-z and BMI-height age-z were determined using the 2000 Centers for Disease Control and Prevention reference data. RESULTS: Compared with healthy children of the same sex, age, race, and BMI-age-z, LM-height-z was significantly higher in males with all CKD stages (by 0.41-0.43 SDs) and in females with mild to moderate CKD (by 0.38 SD); FM-height-z was significantly higher in both males (by 0.26 SD) and females (by 0.52 SD) with severe CKD. Underestimation of relative LM and adiposity was improved by expressing BMI relative to height-age. CONCLUSIONS: In children with CKD, BMI-height-age-z reflects relative LM and adiposity in the same way that BMI age-z does in healthy children. PMID- 22300739 TI - Randomized trial assessing the effects of ergocalciferol administration on circulating FGF23. AB - BACKGROUND AND OBJECTIVES: Fibroblast growth factor 23 is a phosphate- and vitamin D-regulating hormone. The objective of this study was to determine the effect of ergocalciferol administration on fibroblast growth factor 23 levels in healthy vitamin D-deficient subjects. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this 12-week trial conducted in a clinical research center, 18- to 45-year-old subjects (n=90) with 25-hydroxyvitamin D levels <=20 ng/ml (by chemiluminescent immunoassay) were randomized to weekly ergocalciferol treatment of 50,000 international units or placebo, while consuming a self-selected diet. Changes in fibroblast growth factor 23, 25-hydroxyvitamin D (by liquid chromatography/tandem mass spectroscopy), 1,25-dihydroxyvitamin D, parathyroid hormone, and serum phosphate were measured. RESULTS: Mean 25-hydroxyvitamin D (P<0.0001), 1,25-dihydroxyvitamin D (P=0.01), and fibroblast growth factor 23 (P=0.003) increased in the treatment versus placebo group. In the treatment group, 25-hydroxyvitamin D increased from 18 +/- 7 to 40 +/- 12 ng/ml at week 4 (P<0.0001) and remained stable at 43 +/- 12 ng/ml at week 12 (P<0.0001); 1,25 dihydroxyvitamin D increased from 42 +/- 17 to 52 +/- 18 pg/ml at week 4 (P<0.001) and then remained stable, and fibroblast growth factor 23 increased from 43 +/- 17 to 60 +/- 33 pg/ml at week 8 (P=0.001) and 74 +/- 42 pg/ml at week 12 (P<0.0001). Urinary phosphate excretion increased within the treatment group, but parathyroid hormone and serum phosphate were unchanged. CONCLUSIONS: Ergocalciferol administration increases circulating fibroblast growth factor 23. When measuring fibroblast growth factor 23, concurrent 25-hydroxyvitamin D measurements should be obtained, because vitamin D deficiency may lower circulating fibroblast growth factor 23 levels. PMID- 22300740 TI - A computerized treatment algorithm trial to optimize mineral metabolism in ESRD. AB - BACKGROUND AND OBJECTIVES: Achievement of mineral targets in patients receiving dialysis remains challenging. This study sought to evaluate outcomes for phosphorus, calcium, and parathyroid hormone when a dialysis population was switched from a predominantly active vitamin D analogue treatment regimen to a computerized algorithm incorporating both cinacalcet and active vitamin D as potential first-line therapies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This longitudinal prospective trial enrolled 92 patients undergoing maintenance hemodialysis. Baseline measures (the average of the 3 months before computerized algorithm implementation) were compared with the proportion of patients achieving the prespecified targets at 6 and 12 months. RESULTS: After 6 months there was a statistically significant improvement in the percentage of patients achieving the primary and secondary phosphorus targets (primary: phosphorus <= 5.5 mg/dl, increase from 41% to 75%, P<0.001; secondary: phosphorus 3.0-4.6 mg/dl, increase from 16% to 38%; P=0.005). These improvements were sustained at 12 months. There was a statistically significant improvement in the percentage of patients achieving all three prespecified secondary endpoints (an increase from 12.8% to 25.6% at 12 months; P=0.04); however, this was mainly driven by improved phosphorus control. The proportion of patients achieving the primary or secondary parathyroid hormone targets did not improve. CONCLUSIONS: A greater proportion of dialysis patients achieved improved phosphorus but not parathyroid hormone control by switching from a predominantly active vitamin D analogue-based treatment regimen for mineral and bone disorder to a computer-driven algorithm that incorporated cinacalcet and low-dose active vitamin D analogues as first line therapy. PMID- 22300742 TI - Human papillomavirus distribution in vulvar intraepithelial neoplasia. AB - This pilot study investigated the prevalence and distribution of human papillomavirus (HPV) type in vulvar lesions in women with a history of vulvar intraepithelial neoplasia. Fifty-two specimens were collected. Uncommon HPV subtypes were found among the specimens, which may have implications for HPV vaccination coverage. PMID- 22300741 TI - Semiquantitative analysis of maximum standardized uptake values of regional lymph nodes in inflammatory breast cancer: is there a reliable threshold for differentiating benign from malignant? AB - RATIONALE AND OBJECTIVES: The aim of this study was to determine an optimum standardized uptake value (SUV) threshold for identifying regional nodal metastasis on 18F-fluorodeoxyglucose (FDG) positron emission tomographic (PET)/computed tomographic (CT) studies of patients with inflammatory breast cancer. MATERIALS AND METHODS: A database search was performed of patients newly diagnosed with inflammatory breast cancer who underwent 18F-FDG PET/CT imaging at the time of diagnosis at a single institution between January 1, 2001, and September 30, 2009. Three radiologists blinded to the histopathology of the regional lymph nodes retrospectively analyzed all 18F-FDG PET/CT images by measuring the maximum SUV (SUVmax) in visually abnormal nodes. The accuracy of 18F-FDG PET/CT image interpretation was correlated with histopathology when available. Receiver-operating characteristic curve analysis was performed to assess the diagnostic performance of PET/CT imaging. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated using three different SUV cutoff values (2.0, 2.5, and 3.0). RESULTS: A total of 888 regional nodal basins, including bilateral axillary, infraclavicular, internal mammary, and supraclavicular lymph nodes, were evaluated in 111 patients (mean age, 56 years). Of the 888 nodal basins, 625 (70%) were negative and 263 (30%) were positive for metastasis. Malignant lymph nodes had significantly higher SUVmax than benign lymph nodes (P < .0001). An SUVmax of 2.0 showed the highest overall sensitivity (89%) and specificity (99%) for the diagnosis of malignant disease. CONCLUSIONS: SUVmax of regional lymph nodes on 18F-FDG PET/CT imaging may help differentiate benign and malignant lymph nodes in patients with inflammatory breast cancer. An SUV cutoff of 2 provided the best accuracy in identifying regional nodal metastasis in this patient population. PMID- 22300743 TI - The use of hyaluronan to regulate protein adsorption and cell infiltration in nanofibrous scaffolds. AB - Electrospun nanofibers are prepared with mixtures of natural and synthetic polymers that can behave cooperatively to demonstrate combinations of mechanical, structural and biochemical properties for tissue engineering applications. However, the large surface area and inherent small pores of these structures give nanofibrous scaffolds high non-specific protein adsorption and poor cell infiltration. In this study, we developed a protein resistant and porous nanofibrous scaffold composed of hyaluronan (HA), silk fibroin (SF), and polycaprolactone (PCL) blends via one-step emulsion electrospinning. The scaffolds were characterized and evaluated for nanostructures, chemical composition, mechanical properties, hydrophilicity, and protein adsorption. Swelling and degradation studies revealed the formation of oriented pore structures within the body of the scaffolds and increasing the pore size between fibers. Addition of HA component transformed current PCL/SF components into hydrophilic fibers, which caused the suppression of non-specific protein adsorption, resulting in the reduction of fibrosis tissue thickness and macrophages adhesion in vivo. Importantly, HA-based scaffolds significantly enhanced cell infiltration in vitro and tissue ingrowth in vivo. In vitro cultivation of human primary skin fibroblasts on the HA-based scaffolds showed a significant increase in cell proliferation and filopodia protrusions, but decreased in collagen I production. Furthermore, HA and HA-based scaffolds interacted with cell surface receptor CD44 to activate TGF-beta1/MMPs signaling pathways that conducive to cell migration. These findings suggest that such an HA based nanofibrous scaffold resists protein adsorption and enhances cell infiltration, may offer possibilities to overcome the limitations of electrospinning technology. PMID- 22300744 TI - Ion-induced cell sheet detachment from standard cell culture surfaces coated with polyelectrolytes. AB - Polyelectrolyte multilayers (PEMs), formed by alternating layer-by-layer deposition of polyanions and polycations, are an ideal substrate for controlling cellular adhesion and behavior. In the present study we propose a simple mechanism for the controlled detachment of C(2)C(12) myoblasts cell sheets from PEMs consisting of poly(l-lysine) and hyaluronic acid with a topmost layer of fibronectin. The multilayers were deposited on two standard cell culture surfaces: glass and polystyrene. Adding a low concentration of nontoxic ferrocyanide to the cell culture medium resulted in erosion of the polyelectrolyte multilayer and rapid detachment of viable cell sheets. Additional Quartz Crystal Microbalance and Atomic Force Microscopy measurements indicated that the detached cells retained their extracellular matrix and that no polyelectrolyte molecules remained bound to the cell sheets. The dissolution of polyelectrolyte multilayers by multivalent ions is a promising approach to cell sheet engineering that could potentially be used for regenerative medicine. PMID- 22300745 TI - Involvement of descending serotonergic and noradrenergic pathways in CB1 receptor mediated antinociception. AB - Cannabinoids produce antinociceptive and antihyperalgesic effects mainly through activation of the inhibitory CB1 receptors. The demonstration that antinociceptive effects of systemic cannabinoids are significantly diminished following surgical dorsolateral funiculus lesion provides evidence that supraspinal sites and descending pain modulatory pathways play crucial roles in systemic cannabinoid analgesia. In this review, we will firstly provide a background, brief overview of descending modulatory pathways followed by descending pathways implicated in cannabinoid analgesia. We will then describe the recent evidence of the involvement of descending serotonergic and noradrenergic pathways in CB1 receptor-mediated antinociception. This review will provide evidences that systemically administered cannabinoids reinforce the descending serotonergic and noradrenergic pathways to produce acute antinociceptive effects via spinal 5-HT7, 5-HT2A and alpha-2 adrenoceptors activation. PMID- 22300746 TI - Interactions between the cannabinoid and dopaminergic systems: evidence from animal studies. AB - There is a prominent role of the cannabinoid system to control basal ganglia function, in respect to reward, psychomotor function and motor control. Cannabinoid dysregulations might have a pathogenetic role in dopamine- and basal ganglia related neuropsychiatric disorders, such as drug addiction, psychosis, Parkinson's disease and Huntington's disease. This review highlights interactions between cannabinoids, and dopamine, to modulate neurotransmitter release and synaptic plasticity in the context of drug addiction, psychosis and cognition. Modulating endocannabinoid function, as a plasticity based therapeutic strategy, in the above pathologies with particular focus on cannabinoid receptor type 1 (CB1 receptor) antagonists/inverse agonists, is discussed. On the basis of the existing literature and of new experimental evidence presented here, CB1 receptor antagonists might be beneficial in disease states associated with hedonic dysregulation, and with cognitive dysfunction in particular in the context of psychosis. It is suggested that this effects might be mediated via a hyperglutamatergic state through metabotropic glutamate activation. Indications for endocannabinoid catabolism inhibitors in psychiatric disorders, that might be CB1 receptor independent and might involve TRPV1 receptors, are also discussed. PMID- 22300747 TI - Agmatine, an endogenous ligand of imidazoline receptor protects against memory impairment and biochemical alterations in streptozotocin-induced diabetic rats. AB - Agmatine, a polycationic amine synthesized via decarboxylation of l-arginine by arginine decarboxylase is reported to exhibit anti-hyperglycemic, antioxidant and memory enhancing effects. Therefore, we tested its influence against cognitive dysfunction in streptozotocin-induced diabetic rats using Morris water maze and object recognition paradigm. Lipid peroxidation and glutathione levels as parameters of oxidative stress and choline esterase (ChE) activity as a marker of cholinergic function were assessed in the cerebral cortex and hippocampus. Thirty days after diabetes induction rats showed a severe deficit in learning and memory associated with increased lipid peroxidation, decreased reduced glutathione, and elevated ChE activity. In contrast, chronic treatment with agmatine (5-10mg/kg, i.p. for 30 days) improved cognitive performance, lowered hyperglycemia, oxidative stress, and ChE activity in diabetic rats. Further, memory improving effects of agmatine were independent of adrenal I(2) imidazoline receptors. In a separate set, agmatine treatment for an initial 15 days after diabetes confirmation also significantly reduced memory impairment during training trials after 30 days of diabetes confirmation. Moreover, treatment during training trials (30 days after diabetes) also significantly reduced memory impairment in diabetic rats. In conclusion, the present study demonstrates that treatment with agmatine prevents changes in oxidative stress and ChE activity, and probably consequent memory impairment in diabetic rats. PMID- 22300748 TI - Algorithm for the diagnosis and treatment of pediatric OSA: a proposal of two pediatric sleep centers. AB - There is currently no consensus on the best method of managing of obstructive sleep apnea (OSA) in childhood. In the present paper, an algorithm for the diagnosis and treatment of the disorder is proposed. Sleep apnea is suspected when parents report relevant symptoms or when there are abnormalities that predispose to OSA such as adenotonsillar hypertrophy, obesity, craniofacial anomalies, or neuromuscular disorders. OSA-associated morbidity including elevated blood pressure, daytime sleepiness or learning problems, growth failure, and enuresis should be recognized. Severity of intermittent upper airway obstruction during sleep can be determined objectively by polysomnography or, if polysomnography is not available, by nocturnal pulse oximetry. Risk factors predicting persistence of OSA in adolescence (male gender, development of obesity) need to be identified. Children with moderate-to-severe OSA, or with mild OSA, but accompanied by morbidity, or by risk factors predicting persistence of the disorder should have priority for treatment. An individualized and multifaceted therapeutic approach which addresses in a step-by-step fashion all abnormalities that contribute to upper airway obstruction during sleep is necessary. PMID- 22300749 TI - Somatic comorbidity in anorexia nervosa: First results of a 21-year follow-up study on female inpatients. AB - BACKGROUND: Anorexia nervosa is a severe psychosomatic disease with somatic complications in the long-term course and a high mortality rate. Somatic comorbidities independent of anorexia nervosa have rarely been studied, but pose a challenge to clinical practitioners. We investigated somatic comorbidities in an inpatient cohort and compared somatically ill anorexic patients and patients without a somatic comorbidity. In order to evaluate the impact of somatic comorbidity for the long-term course of anorexia nervosa, we monitored survival in a long-term follow-up. METHOD: One hundred and sixty-nine female inpatients with anorexia nervosa were treated at the Charite University Medical Centre, Campus Benjamin Franklin, Berlin, between 1979 and 2011. We conducted retrospective analyses using patient's medical and psychological records. Information on survival and mortality were required through the local registration office and was available for one hundred patients. The mean follow up interval for this subgroup was m = 20.9 years (sd = 4.7, min = 13.3, max = 31.6, range = 18.3). We conducted survival analysis using cox regression and included somatic comorbidity in a multivariate model. RESULTS: N = 41 patients (24.3%) showed a somatic comorbidity, n = 13 patients (7.7%) showed somatic comorbidities related to anorexia nervosa and n = 26 patients (15.4%) showed somatic comorbidities independent of anorexia nervosa, n = 2 patients showed somatic complications related to other psychiatric disorders. Patients with a somatic comorbidity were significantly older (m = 29.5, sd = 10.3 vs m = 25.0, sd = 8.7; p = .006), showed a later anorexia nervosa onset (m = 24.8, sd = 9.9 vs. m = 18.6, sd = 5.1; p < .000) and a longer duration of treatment in our clinic (m = 66.6, sd = 50.3 vs. m = 50.0, sd = 47; p = .05) than inpatients without somatic comorbidity. Out of 100 patients, 9 patients (9%) had died, on average at age of m = 37 years (sd = 9.5). Mortality was more common among inpatients with somatic comorbidity (n = 6, 66.7%) than among inpatients without a somatic disease (n = 3, 33.3%; p = .03). Somatic comorbidity was a significant coefficient in a multivariate survival model (B = 2.32, p = .04). CONCLUSION: Somatic comorbidity seems to be an important factor for anorexia nervosa outcome and should be included in multivariate analyses on the long-term course of anorexia nervosa as an independent variable. Further investigations are needed in order to understand in which way anorexia nervosa and a somatic disease can interact. PMID- 22300750 TI - Stereotactic body radiotherapy (SBRT) for solitary pulmonary nodules clinically diagnosed as lung cancer with no pathological confirmation: comparison with non small-cell lung cancer. AB - INTRODUCTION: In non-surgical candidates with solitary pulmonary nodules (SPNs) and no histological confirmation, optimal management remains uncertain. METHODS: Between February 2005 and February 2011 we treated 298 lung cancers with stereotactic body radiotherapy (SBRT), including SPNs clinically diagnosed as lung cancer (CDLC). Among them, we extracted patients treated with a total dose of 40-50 Gy per 5 fractions and followed up more than 6 months. Patients who had a history of previously treated lung cancer, or were diagnosed pathologically, or suspected as having small-cell lung cancer or large cell neuroendcrine cancer were excluded from this study. The remaining patients were divided into two groups; CDLC and non-small-cell lung cancer (NSCLC) patients and their outcomes were assessed and compared. RESULTS: Fifty-eight CDLC and 115 NSCLC patients were included in this study. The proportions of female and inoperable cases were significantly higher in the CDLC group. Other characteristics, including T stage and standard uptake value, were well balanced. Median follow-up durations were 20.2 (range, 6.0-58.8) and 21.2 (range, 6-63.7) months, respectively. The 3-year local control, regional-free, metastasis-free, progression-free, cause-specific survival, and overall survival rates were 80% and 87% (p = 0.73), 88% and 91% (p = 0.72), 70% and 74% (p = 0.57), 64% and 67% (p = 0.45), 74% and 71% (p = 0.17), 54% and 57% (p = 0.48), respectively. CONCLUSION: These results indicate that the treatment outcome of CDLC group was almost identical to that of NSCLC and that few benign lesions seemed to be included. We advocate that SBRT can be legitimately applied to CDLC, provided that they are carefully diagnosed by integrating various clinical findings. PMID- 22300751 TI - Stromal CD4/CD25 positive T-cells are a strong and independent prognostic factor in non-small cell lung cancer patients, especially with adenocarcinomas. AB - Within the concert of immune reactions against tumour cells cytotoxic and regulatory T-cells are of utmost importance. Several studies revealed contradictory results on this issue. We therefore focused on functional expression patterns and localization of tumour-infiltrating T-lymphocytes in non small cell lung cancer (NSCLC) and their impact on patient's survival. 232 curatively operated NSCLC patients were included. After histological reevaluation and construction of tissue-multi-arrays immunohistochemical doublestains for CD3/CD8 and CD4/CD25 were performed to evaluate the total number of T-cells and their subsets of cytotoxic and activated T-cells. Additionally, the localization of the lymphocytes was included in the analysis. Hereby, T-cells within the tumour stroma were regarded as stromal, those among cancer cells as intraepithelial. The number of lymphocytes differed significantly between the histological subtypes being most prominent in large cell carcinomas. Survival analysis showed that high numbers of stromal T-lymphocytes are of beneficial prognostic influence in NSCLC patients. This also proved to be an independent prognostic factor in adenocarcinomas. Thus, in a large and well characterized cohort of NSCLC this is the first study to determine the prognostic value of stromal T-lymphocytes, as these are an independent prognosticator in NSCLC especially in adenocarcinomas whereas intraepithelial T-cells are not. PMID- 22300752 TI - Correlations between serial pro-gastrin-releasing peptide and neuron-specific enolase levels, and the radiological response to treatment and survival of patients with small-cell lung cancer. AB - INTRODUCTION: To investigate whether decrease in the serum levels of pro-gastrin releasing peptide (ProGRP) and neuron-specific enolase (NSE) were correlated with the radiological response in patients with small-cell lung cancer (SCLC). METHODS: Of the 196 patients, we retrospectively reviewed 118 patients elevated baseline levels of ProGRP and NSE prior to the initial therapy (IT) who survived for more than 1 month. The radiological response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST 1.1). RESULTS: Decrease in the serum ProGRP was strongly correlated with the decrease of the sum of the tumor diameters (SOD) before the third course (rho=0.50) and after the fourth course (rho=0.42) of IT. Decrease in the serum NSE was weakly correlated with the decrease of the SOD after the fourth course (rho=0.27), but not before the third courses (rho=0.22). In the receiver operating characteristic (ROC) curves predicting 1-year survivors, the area under the curve (AUC) for percent changes in serum ProGRP before the third course were significantly larger than those for NSE (0.714 vs. 0.527, p=0.004). CONCLUSIONS: Percent changes in serum ProGRP showed better correlation to SOD and prognostic impact than that of NSE. PMID- 22300753 TI - Antivirals for management of herpes zoster including ophthalmicus: a systematic review of high-quality randomized controlled trials. AB - BACKGROUND: There is lack of consensus from randomized controlled trials on the efficacy of antivirals in the management of herpes zoster. Therefore, a systematic review and meta-analysis was undertaken to provide better understanding of effectiveness of antivirals in management of herpes zoster. METHODS: A total of 12 randomized controlled trials with 7,277 patients were included in the review. Trials compared one antiviral to another (aciclovir, valaciclovir, famciclovir or brivudin) for a minimum of 7 days in immunocompetent patients presenting with herpes zoster diagnosed within 72 h of symptom onset. Primary outcome was reduction in pain. RESULTS: Compared with aciclovir, valaciclovir showed significant reduction in herpes-zoster-associated pain up to 112 days. The largest risk reduction in pain (36%) was seen at 21-30 days (relative risk [RR] 0.64, 95% CI 0.59, 0.70) with number needed to treat to benefit (NNT) of 3 (95% CI 2.7, 3.8). Famciclovir was also superior to aciclovir with a 46% reduction in risk of pain at 28-30 days (RR 0.54, 95% CI 0.48, 0.68) with NNT of 3 (95% CI 2, 5). Time to lesion healing and adverse effect profile was comparable. CONCLUSIONS: Evidence from quality trials have shown significant reduction in risk of pain with valaciclovir and famciclovir for management of herpes zoster including ophthalmicus. Valaciclovir or famciclovir should be preferred treatment options in patients with herpes zoster as they both provide significant reduction in risk of herpes-zoster-associated pain. Furthermore, the superior pharmacokinetics and more convenient dosing regimens with the use of valaciclovir and famciclovir clearly make them the preferred treatment option. PMID- 22300754 TI - Simultaneous expression of recombinant proteins in the insect cell-baculovirus system: production of virus-like particles. AB - The insect cell-baculovirus system (IC-BEVS) is widely used for the production of recombinant viral proteins for vaccine applications. It is especially suitable for the production of virus-like particles, which often require the simultaneous production of several recombinant proteins. Here, the available tools and process requirements for the simultaneous production of several recombinant proteins using the IC-BEVS are discussed. The production of double-layered rotavirus like particles is used as a specific example for the simultaneous production of two recombinant proteins. Methods to quantify VLP in small samples are described. The multiplicity and time of infection are presented as tools to manipulate protein concentration, and the effect on protein concentration ratios on the assembly efficiency of double-layered rotavirus like particles is discussed. It was found that not only the ratio between the recombinant proteins is determinant of VLP assembly efficiency, but also that assembly efficiency is related to the characteristics of the assembled proteins. This is the first time that kinetics of VLP production are followed during cultures, and that the assembly efficiency is quantitatively determined. PMID- 22300755 TI - Detailed biopsy pathologic features as predictive factors for initial reclassification in prostate cancer patients eligible for active surveillance. AB - OBJECTIVE: To evaluate the impact of detailed biopsy characteristics such as positive cores location or multifocality on the risk of initial reclassification in prostate cancer (CaP) patients eligible for active surveillance (AS). MATERIALS AND METHODS: We reviewed data from 300 consecutive men eligible for AS (PSA <= 10 ng/ml, clinical stage T1c, Gleason score <= 6, <3 positive cores, extent of cancer in any core < 50%) who have undergone a radical prostatectomy (RP). Reclassification was defined as upstaged disease and/or upgraded disease in RP specimens. RESULTS: Biopsy features showed 36% of CaP involving 2 cores and a mean total tumor length of 2.63 mm. The 2 most frequently positive sites were base and apex. Mean total tumor length was significantly associated with upgraded disease (P = 0.025). In a multivariate model taking into account PSA, PSAD, number of positive cores and total tumor length, a total tumor length > 5 mm were independently predictor for a upgraded disease (OR 1.93, P = 0.046). The number, the multifocality and the bilaterality of positive cores were not associated with reclassification. Upgraded disease was significantly less reported in case of positivity at midline zone compared with positivity at base, apex, or transition zone (P = 0.013). CONCLUSIONS: Detailed biopsy data provide additional information on the initial risk of reclassification in AS patients. Patients having a total tumor length < 5 mm and positive cores at midline zone are more likely to have favorable pathologic characteristics at diagnosis. These variables can be used for selection and monitoring improvement in AS programs. PMID- 22300756 TI - Summary of the 6th Annual Bladder Cancer Think Tank: new directions in urologic research. AB - The 6th Annual Bladder Cancer Think Tank brought together a multidisciplinary group of clinicians, researchers, and representatives from the National Cancer Institute and Industry in an effort to advance bladder cancer research efforts. This year's meeting comprised panel discussions and research involving 5 separate working groups, including the Survivorship, Clinical Trials, Standardization of Care, Data Mining, and Translational Science working groups. In this manuscript, the accomplishments and objectives of the working groups are summarized. Notable efforts include: (1) the development of a survivorship care plan for early and late-stage bladder cancer; (2) the development of consensus criteria for eligibility and endpoints for bladder cancer clinical trials; (3) an improved understanding of current practice patterns regarding the use of perioperative chemotherapy in an effort to standardize care; (4) creation of a comprehensive handbook to assist researchers with developing bladder cancer databases; and (5) identification of response to therapy of high-grade non muscle invasive disease through a collaborative exchange of expertise and resources. PMID- 22300757 TI - Ureterorenoscopic biopsy and urinary cytology according to the 2004 WHO classification underestimate tumor grading in upper urinary tract urothelial carcinoma. AB - OBJECTIVES: To determine accuracy of upper tract cytology and ureteroscopic biopsy according to the 2004 World Health Organization (WHO) classification in predicting the correct tumor grade in patients with urothelial cancer of the upper urinary tract (UUT-UC). METHODS: Pathology reports of 77 nephroureterectomy specimens were retrospectively analyzed for tumor grade and compared with preoperatively gained cytology and ureteroscopic biopsy results. For analysis, the 2004 WHO classification was used. RESULTS: Overall sensitivity of cytology and biopsy in diagnosis of UUT-UC was 64% and 74%, respectively. Accuracy of cytology and biopsy in predicting high grade cancer was 53% and 58%, respectively. Combination of cytology and biopsy could improve sensitivity (84%) and accuracy (68%), but even for this combination, 15% of high grade tumors were misinterpreted as low grade cancer. CONCLUSION: Our results show only limited accuracy for preoperative cytology and ureterorenoscopically performed biopsies in the prediction of the correct tumor grading of an UUT-UC. Therefore, we suggest the use of additional diagnostic procedures before the decision for definitive surgical treatment in patients with UUT-UC is made. PMID- 22300758 TI - A metabolic network approach for the identification and prioritization of antimicrobial drug targets. AB - For many infectious diseases, novel treatment options are needed in order to address problems with cost, toxicity and resistance to current drugs. Systems biology tools can be used to gain valuable insight into pathogenic processes and aid in expediting drug discovery. In the past decade, constraint-based modeling of genome-scale metabolic networks has become widely used. Focusing on pathogen metabolic networks, we review in silico strategies used to identify effective drug targets and highlight recent successes as well as limitations associated with such computational analyses. We further discuss how accounting for the host environment and even targeting the host may offer new therapeutic options. These systems-level approaches are beginning to provide novel avenues for drug targeting against infectious agents. PMID- 22300759 TI - Diverse microbial interactions with the basement membrane barrier. AB - During primary contact with susceptible hosts, microorganisms face an array of barriers that thwart their invasion process. Passage through the basement membrane (BM), a 50-100-nm-thick crucial barrier underlying epithelia and endothelia, is a prerequisite for successful host invasion. Such passage allows pathogens to reach nerve endings or blood vessels in the stroma and to facilitate spread to internal organs. During evolution, several pathogens have developed different mechanisms to cross this dense matrix of sheet-like proteins. To breach the BM, some microorganisms have developed independent mechanisms, others hijack host cells that are able to transverse the BM (e.g. leukocytes and dendritic cells) and oncogenic microorganisms might even trigger metastatic processes in epithelial cells to penetrate the underlying BM. PMID- 22300760 TI - Synthesis of a sulfonic acid mimetic of the sulfated Lewis A pentasaccharide. AB - The first sulfonic acid mimetic of the sulfated Lewis A pentasaccharide in which the natural L-fucose unit is replaced by a D-arabinose ring was synthesized. Formation of the sulfonic acid moiety at a pentasaccharide level could be successfully achieved by means of introduction of an acetylthio moiety into the terminal D-galactose residue and subsequent oxidation. The equatorial arrangement of the acetylthio group linked to C-3 of the galactose ring could be obtained by double nucleophilic substitutions; efficient formation of the gulo-triflate derivatives required low-power microwave (MW) activation. Oxidation of the acetylthio group was carried out using Oxone in the presence of acetic acid. PMID- 22300761 TI - World Diabetes Congress, Dubai--4th-8th December, 2011--commentary from a UK perspective. PMID- 22300762 TI - Dimensional quantification of embedded voids or objects in three dimensions using X-ray tomography. AB - Scientific digital imaging in three dimensions such as when using X-ray computed tomography offers a variety of ways to obtain, filter, and quantify data that can produce vastly different results. These opportunities, performed during image acquisition or during the data processing, can include filtering, cropping, and setting thresholds. Quantifying features in these images can be greatly affected by how the above operations are performed. For example, during binarization, setting the threshold too low or too high can change the number of objects as well as their measured diameter. Here, two facets of three-dimensional quantification are explored. The first will focus on investigating the question of how many voxels are needed within an object to have accurate geometric statistics that are due to the properties of the object and not an artifact of too few voxels. These statistics include but are not limited to percent of total volume, volume of the individual object, Feret shape, and surface area. Using simple cylinders as a starting point, various techniques for smoothing, filtering, and other processing steps can be investigated to aid in determining if they are appropriate for a specific desired statistic for a real dataset. The second area of investigation is the influence of post-processing, particularly segmentation, on measuring the damage statistics in high purity Cu. The most important parts of the pathways of processing are highlighted. PMID- 22300763 TI - Structural basis of substrate binding specificity revealed by the crystal structures of polyamine receptors SpuD and SpuE from Pseudomonas aeruginosa. AB - The type III secretion system (T3SS) of Pseudomonas aeruginosa is a key virulence determinant whose expression is induced by polyamine signals from mammalian host. SpuD and SpuE were postulated to be spermidine-preferential binding proteins, which regulate the polyamine content in this bacterial pathogen. In this study, we found that SpuD is a putrescine-preferential binding protein, while SpuE binds to spermidine exclusively. We have determined the crystal structures of SpuD in free form and in complex with putrescine and SpuE in free form and in complex with spermidine. Upon ligand binding, SpuD and SpuE undergo an "open-to-closed" conformational switch with the resultant closed ligand-bound forms, SpuD putrescine and SpuE-spermidine, similar to their Escherichia coli counterparts PotF-putrescine and PotD-spermidine, respectively. Structural comparison suggested that two aromatic residues, Trp271 of SpuE and Phe273 of SpuD in segment II region, are the key structural determinants for putrescine/spermidine recognition specificity. Mutagenesis combined with isothermal titration calorimetry showed that substitution of Trp271 by Phe enabled SpuE to gain substantial binding affinity for putrescine, while replacement of Phe273 by Trp reduced the binding affinity of SpuD toward putrescine by 250-fold. Altogether, these results revealed the molecular mechanism governing polyamine recognition specificity by SpuD and SpuE and provide the basis for further structural and functional studies of polyamine signal importation system in P. aeruginosa. PMID- 22300764 TI - CNP-1 (ARRD-17), a novel substrate of calcineurin, is critical for modulation of egg-laying and locomotion in response to food and lysine sensation in Caenorhabditis elegans. AB - Calcineurin is a Ca(2+)/calmodulin-dependent protein phosphatase involved in calcium signaling pathways. In Caenorhabditis elegans, the loss of calcineurin activity causes pleiotropic defects including hyperadaptation of sensory neurons, hypersensation to thermal difference and hyper-egg-laying when worms are refed after starvation. In this study, we report on arrd-17 as calcineurin-interacting protein-1 (cnp-1), which is a novel molecular target of calcineurin. CNP-1 interacts with the catalytic domain of the C. elegans calcineurin A subunit, TAX 6, in a yeast two-hybrid assay and is dephosphorylated by TAX-6 in vitro. cnp-1 is expressed in ASK, ADL, ASH and ASJ sensory neurons as TAX-6. It acts downstream of tax-6 in regulation of locomotion and egg-laying after starvation, ASH sensory neuron adaptation and lysine chemotaxis, that is known to be mediated by ASK neurons. Altogether, our biochemical and genetic evidence indicates that CNP-1 is a direct target of calcineurin and required in stimulated egg-laying and locomotion after starvation, adaptation to hyperosmolarity and attraction to lysine, which is modulated by calcineurin. We suggest that the phosphorylation status of CNP-1 plays an important role in regulation of refed stimulating behaviors after starvation and attraction to amino acid, which provides valuable nutritious information. PMID- 22300765 TI - Structural properties of EGCG-induced, nontoxic Alzheimer's disease Abeta oligomers. AB - The green tea compound epigallocatechin-3-gallate (EGCG) inhibits Alzheimer's disease beta-amyloid peptide (Abeta) neurotoxicity. Solution-state NMR allows probing initial EGCG-Abeta interactions. We show that EGCG-induced Abeta oligomers adopt a well-defined structure and are amenable for magic angle spinning solid-state NMR investigations. We find that EGCG interferes with the aromatic hydrophobic core of Abeta. The C-terminal part of the Abeta peptide (residues 22-39) adopts a beta-sheet conformation, whereas the N-terminus (residues 1-20) is unstructured. The characteristic salt bridge involving residues D23 and K28 is present in the structure of these oligomeric Abeta aggregates as well. The structural analysis of small-molecule-induced amyloid aggregates will open new perspectives for Alzheimer's disease drug development. PMID- 22300766 TI - VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. AB - Cancer is a disease driven by genetic variation and mutation. Exome sequencing can be utilized for discovering these variants and mutations across hundreds of tumors. Here we present an analysis tool, VarScan 2, for the detection of somatic mutations and copy number alterations (CNAs) in exome data from tumor-normal pairs. Unlike most current approaches, our algorithm reads data from both samples simultaneously; a heuristic and statistical algorithm detects sequence variants and classifies them by somatic status (germline, somatic, or LOH); while a comparison of normalized read depth delineates relative copy number changes. We apply these methods to the analysis of exome sequence data from 151 high-grade ovarian tumors characterized as part of the Cancer Genome Atlas (TCGA). We validated some 7790 somatic coding mutations, achieving 93% sensitivity and 85% precision for single nucleotide variant (SNV) detection. Exome-based CNA analysis identified 29 large-scale alterations and 619 focal events per tumor on average. As in our previous analysis of these data, we observed frequent amplification of oncogenes (e.g., CCNE1, MYC) and deletion of tumor suppressors (NF1, PTEN, and CDKN2A). We searched for additional recurrent focal CNAs using the correlation matrix diagonal segmentation (CMDS) algorithm, which identified 424 significant events affecting 582 genes. Taken together, our results demonstrate the robust performance of VarScan 2 for somatic mutation and CNA detection and shed new light on the landscape of genetic alterations in ovarian cancer. PMID- 22300767 TI - Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques. AB - Over the course of ontogenesis, the human brain and human cognitive abilities develop in parallel, resulting in a phenotype strikingly distinct from that of other primates. Here, we used microarrays and RNA-sequencing to examine human specific gene expression changes taking place during postnatal brain development in the prefrontal cortex and cerebellum of humans, chimpanzees, and rhesus macaques. We show that the most prominent human-specific expression change affects genes associated with synaptic functions and represents an extreme shift in the timing of synaptic development in the prefrontal cortex, but not the cerebellum. Consequently, peak expression of synaptic genes in the prefrontal cortex is shifted from <1 yr in chimpanzees and macaques to 5 yr in humans. This result was supported by protein expression profiles of synaptic density markers and by direct observation of synaptic density by electron microscopy. Mechanistically, the human-specific change in timing of synaptic development involves the MEF2A-mediated activity-dependent regulatory pathway. Evolutionarily, this change may have taken place after the split of the human and the Neanderthal lineages. PMID- 22300768 TI - Copy number variation of individual cattle genomes using next-generation sequencing. AB - Copy number variations (CNVs) affect a wide range of phenotypic traits; however, CNVs in or near segmental duplication regions are often intractable. Using a read depth approach based on next-generation sequencing, we examined genome-wide copy number differences among five taurine (three Angus, one Holstein, and one Hereford) and one indicine (Nelore) cattle. Within mapped chromosomal sequence, we identified 1265 CNV regions comprising ~55.6-Mbp sequence--476 of which (~38%) have not previously been reported. We validated this sequence-based CNV call set with array comparative genomic hybridization (aCGH), quantitative PCR (qPCR), and fluorescent in situ hybridization (FISH), achieving a validation rate of 82% and a false positive rate of 8%. We further estimated absolute copy numbers for genomic segments and annotated genes in each individual. Surveys of the top 25 most variable genes revealed that the Nelore individual had the lowest copy numbers in 13 cases (~52%, chi(2) test; P-value <0.05). In contrast, genes related to pathogen- and parasite-resistance, such as CATHL4 and ULBP17, were highly duplicated in the Nelore individual relative to the taurine cattle, while genes involved in lipid transport and metabolism, including APOL3 and FABP2, were highly duplicated in the beef breeds. These CNV regions also harbor genes like BPIFA2A (BSP30A) and WC1, suggesting that some CNVs may be associated with breed specific differences in adaptation, health, and production traits. By providing the first individualized cattle CNV and segmental duplication maps and genome wide gene copy number estimates, we enable future CNV studies into highly duplicated regions in the cattle genome. PMID- 22300769 TI - Effects of sequence variation on differential allelic transcription factor occupancy and gene expression. AB - A complex interplay between transcription factors (TFs) and the genome regulates transcription. However, connecting variation in genome sequence with variation in TF binding and gene expression is challenging due to environmental differences between individuals and cell types. To address this problem, we measured genome wide differential allelic occupancy of 24 TFs and EP300 in a human lymphoblastoid cell line GM12878. Overall, 5% of human TF binding sites have an allelic imbalance in occupancy. At many sites, TFs clustered in TF-binding hubs on the same homolog in especially open chromatin. While genetic variation in core TF binding motifs generally resulted in large allelic differences in TF occupancy, most allelic differences in occupancy were subtle and associated with disruption of weak or noncanonical motifs. We also measured genome-wide differential allelic expression of genes with and without heterozygous exonic variants in the same cells. We found that genes with differential allelic expression were overall less expressed both in GM12878 cells and in unrelated human cell lines. Comparing TF occupancy with expression, we found strong association between allelic occupancy and expression within 100 bp of transcription start sites (TSSs), and weak association up to 100 kb from TSSs. Sites of differential allelic occupancy were significantly enriched for variants associated with disease, particularly autoimmune disease, suggesting that allelic differences in TF occupancy give functional insights into intergenic variants associated with disease. Our results have the potential to increase the power and interpretability of association studies by targeting functional intergenic variants in addition to protein coding sequences. PMID- 22300770 TI - Increased CD34+/KDR+ cells are not associated with carotid artery intima-media thickness progression in chronic HIV-positive subjects. AB - BACKGROUND: Endothelial progenitor cells (EPCs) are involved in the endothelium repair. Low circulating EPC levels are predictive of cardiovascular events in HIV negative subjects. The impact of HIV infection on EPCs, and the role of EPCs in HIV-associated cardiovascular disease, is not known. We hypothesized that circulating EPCs would be inversely associated with carotid artery intima-media thickness (c-IMT) changes in HIV-infected subjects. METHODS: EPCs (CD34(+)/KDR(+), CD133(+)/KDR(+) and CD34(+)/CD133(+)/KDR(+)) were defined retrospectively by flow cytometry in cryopreserved peripheral blood mononuclear cells collected longitudinally from 66 chronic HIV-infected subjects and cross sectionally from 50 at-risk HIV-negative subjects. The HIV-infected subjects participated in the Study of the Consequences of the Protease Inhibitor Era (SCOPE) cohort, were receiving antiretroviral therapy (59/66) and had two sequential measurements of c-IMT 1 year apart. Two distinct groups of HIV infected subjects were identified a priori: rapid c-IMT progressors (subjects with rapid c-IMT progression, n=13, Deltac-IMT>0.2 mm) and slow c-IMT progressors (subjects with slow or no c-IMT progression, n=53, Deltac-IMT<0.2 mm). RESULTS: Although cryopreservation reduced sensitivity of detection, EPC frequency in HIV infected subjects was still significantly higher compared to at-risk HIV-negative subjects (CD34(+)/KDR(+); P=0.01) and correlated positively with CD4(+) T-cell count (CD34(+)/KDR(+), r=0.27; P=0.03). No association was found between the change of EPC frequencies over time (DeltaEPC) and Deltac-IMT or between EPC frequencies and c-IMT or Deltac-IMT. CONCLUSIONS: The lack of an association between EPCs and c-IMT in our cohort does not support HIV-associated reductions in EPC frequency as a cause of accelerated atherosclerosis. PMID- 22300771 TI - Behavioral interventions for coronary heart disease patients. AB - INTRODUCTION: There is a strong clinical need to provide effective stress reduction programs for patients with an acute coronary syndrome. Such programs for men have been implemented and their cardiovascular health benefit documented. For women such programs are scarce.In this report, The feasibility of a cognitive method that was recently demonstrated to prolong lives of women is tested. A setting with gender segregated groups was applied. METHOD: The principles of a behavioural health educational program originally designed to attenuate the stress of patients with coronary prone behaviours were used as a basis for the intervention method. For the groups of female patients this method was tailored according to female stressors and for the groups of men according to male stressors. The same core stress reduction program was used for women and men, but the contents of discussions and responses to the pre planned program varied. These were continuously monitored throughout the fifteen sessions. Implementation group: Thirty consecutive patients, eleven women and nineteen men, hospitalized for an acute coronary syndrome were included in this intervention. All expressed their need to learn how to cope with stress in daily life and were highly motivated. Five groups, three groups of men and two groups of women were formed. Psychological assessments were made immediately before and after completion of the program. RESULTS: No gender differences in the pre planned programs were found, but discussion styles varied between the women and men, Women were more open and more personal. Family issues were more frequent than job issues, although all women were employed outside their homes. Men talked about concrete and practical things, mostly about their jobs, and not directly about their feelings. Daily stresses of life decreased significantly for both men and women, but more so for women. Depressive thoughts were low at baseline, and there was no change over time. In contrast, anxiety scores were high at baseline and decreased significantly, but more so for women than for men. CONCLUSION: Women are likely to benefit from women's groups. Men may prefer to have one or two women in the group, but women fare better in gender segregated groups. PMID- 22300772 TI - Chemical composition of five wild edible mushrooms collected from Southwest China and their antihyperglycemic and antioxidant activity. AB - Evaluation of the chemical composition and antihyperglycemic and antioxidant activity of five wild edible mushrooms (Clitocybe maxima, Catathelasma ventricosum, Stropharia rugoso-annulata, Craterellus cornucopioides and Laccaria amethystea) from Southwest China. The chemical composition assay includes proximate analysis (moisture, ash, crude protein, crude fat, total carbohydrates and total energy), bioactive compounds analysis (total phenolic, flavonoid, ascorbic acid, ergosterol, tocopherol), fatty acid analysis, amino acid analysis, phenolic compounds analysis and mineral analysis of these mushrooms. Furthermore, assays of alpha-glucosidase inhibitory and alpha-amylase inhibitory activity were used for evaluating antihyperglycemic activity of the mushrooms, and assays of reducing power, chelating effect on ferrous ions, scavenging effect on hydroxyl free radicals and 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity were used for evaluating antioxidant activity of the mushrooms. Based on the results, ethanolic and aqueous extract of these mushroom all showed antihyperglycemic and antioxidant potential. In particular, the aqueous extract of C. ventricosum revealed the highest alpha-glucosidase inhibitory activity (EC50 value 2.74 MUg/mL), DPPH radical scavenging activity (EC50 value 2.86 mg/mL) and reducing power (EC50 value 0.96 mg/mL), while the aqueous extract of L. amethystea showed the highest alpha-amylase inhibitory activity (EC50 value 4.37 MUg/mL) and metal chelating activity (EC50 value 2.13 mg/mL). PMID- 22300773 TI - Gynecologists' characteristics associated with the likelihood of performing laparoscopic-assisted hysterectomy: a nationwide population-based study. AB - OBJECTIVE: With continuing development of minimally invasive techniques in gynecology, hysterectomy with laparoscopic assistance is increasingly performed. This study aimed to examine the relationship between the characteristics of gynecologists and the likelihood of performing laparoscopic-assisted hysterectomy (LH) under the case payment system of Taiwan's National Health Insurance. STUDY DESIGN: A retrospective population-based study was conducted based on the data from Taiwan's National Health Insurance Research Database. A total of 56,532 female residents aged 20 years and older who underwent total hysterectomy with or without laparoscopic assistance between 2004 and 2006 were included in the study. The gender, age and practice volume of their gynecologists were noted. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by univariate and multivariate logistic regression analyses. RESULTS: Of the women selected, 30,478 underwent traditional total hysterectomy (TH) and 26,054 underwent LH. After controlling for clinical and nonclinical factors, male gynecologists (OR 1.65, 95% CI 1.55-1.76) were more likely to perform LH than their female colleagues. Gynecologists aged 60 years and older (OR 0.31, 95% CI 0.29-0.39) had the lowest likelihood of performing LH compared with their counterparts. In addition, surgeons with low-volume practice (OR 0.31, 95% CI 0.29-0.33) also had a significantly lower probability of performing LH compared with other surgeons. CONCLUSION: A higher likelihood of performing LH was observed among male and younger gynecologists with high-volume practice in Taiwan. This finding suggests that differences in practice patterns and surgical treatment decision may explain the variation in the approaches to laparoscopy-assisted hysterectomies. CONDENSATION: Differences in practice patterns and surgical treatment decisions may explain the variation in the approaches to laparoscopic-assisted hysterectomies. PMID- 22300774 TI - On being smart. The value of creativity in research. PMID- 22300775 TI - The Heart Failure Society of America in 2020: a vision for the future. PMID- 22300776 TI - Indications for cardiac resynchronization therapy: 2011 update from the Heart Failure Society of America Guideline Committee. AB - Cardiac resynchronization therapy (CRT) improves survival, symptoms, quality of life, exercise capacity, and cardiac structure and function in patients with New York Heart Association (NYHA) functional class II or ambulatory class IV heart failure (HF) with wide QRS complex. The totality of evidence supports the use of CRT in patients with less severe HF symptoms. CRT is recommended for patients in sinus rhythm with a widened QRS interval (>=150 ms) not due to right bundle branch block (RBBB) who have severe left ventricular (LV) systolic dysfunction and persistent NYHA functional class II-III symptoms despite optimal medical therapy (strength of evidence A). CRT may be considered for several other patient groups for whom evidence of benefit is clinically significant but less substantial, including patients with a QRS interval of >=120 to <150 ms and severe LV systolic dysfunction who have persistent mild to severe HF despite optimal medical therapy (strength of evidence B), some patients with atrial fibrillation, and some with ambulatory class IV HF. Several evidence gaps remain that need to be addressed, including the ideal threshold for QRS duration, QRS morphology, lead placement, degree of myocardial scarring, and the modality for evaluating dyssynchrony. Recommendations will evolve over time as additional data emerge from completed and ongoing clinical trials. PMID- 22300777 TI - Change in intrathoracic impedance measures during acute decompensated heart failure admission: results from the Diagnostic Data for Discharge in Heart Failure Patients (3D-HF) Pilot Study. AB - BACKGROUND: Despite the high number of admissions for acute decompensated heart failure (ADHF), there are no specific criteria for discharge readiness. A number of patients have implantable devices that might provide data to assist in determining readiness for discharge. METHODS AND RESULTS: The 3D-HF (Diagnostic Data for Discharge in Heart Failure Patients) study was a prospective observational pilot study enrolling HF patients with Optivol-capable cardiac devices within 48 hours of a hospital admission characterized by worsening HF symptoms. The primary end point was the difference in times from admission to 50% improvement in impedance and to when patient was medically ready for discharge. The nonparametric sign test was used to determine if the difference was significant. A total of 20 subjects were enrolled over a 24-month period. The median ADHF length of stay was 7 days. Of the 20 subjects, 18 achieved the intrathoracic impedance improvement threshold before discharge. The time to reach the threshold for improvement was 2.5 days (interquartile range 2.0-6.0). The difference between days to 50% impedance and days to provider's discharge decision was 3.0 (P = .0072). CONCLUSIONS: Intrathoracic impedance changes were evident over a short duration in the majority of patients admitted for ADHF and may be a potential criterion for discharge readiness. PMID- 22300778 TI - Trastuzumab adjuvant chemotherapy and cardiotoxicity in real-world women with breast cancer. AB - BACKGROUND: Adjuvant trastuzumab therapy improves survival of human epidermal growth factor receptor 2 (HER2)-positive women with early breast cancer (EBC). A careful monitoring of cardiac function is needed due to potential trastuzumab cardiotoxicity (Tcardiotox). To date, the incidence, timing, and phenotype of patients with Tcardiotox in clinical practice are not well known. METHODS AND RESULTS: A total of 499 consecutive HER2-positive women (mean age 55 +/- 11 years) with EBC treated with trastuzumab between January 2008 and June 2009 at 10 Italian institutions were followed for 1 year. We evaluated incidence, time of occurrence, and clinical features associated with Tcardiotox. Left ventricular ejection fraction (LVEF) was evaluated by echocardiography at baseline and at 3, 6, 9, and 12 months during trastuzumab therapy. Tcardiotox was recognized in 133 patients (27%): 102 (20%) showed asymptomatic reduction in LVEF of >10% but <=20% (grade 1 Tcardiotox); 15 (3%) had asymptomatic decline of LVEF of >20% or <50% (grade 2); and 16 (3%) had symptomatic heart failure (grade 3). Trastuzumab was discontinued due to cardiotoxicity in 24 patients (5%) and restarted in 13 after LVEF recovery. Forty-one percent of Tcardiotox cases occurred within the first 3 months of follow-up, most prevalently in older patients with higher creatinine levels and in patients pretreated with doxorubicin and radiotherapy. CONCLUSIONS: In clinical practice, Tcardiotox is frequent in HER2-positive women with EBC and occurs in the first 3 months of therapy. Cardiac dysfunction is mild and asymptomatic in the majority of patients. The interruption of treatment is a rare event which occurs, however, in a significantly higher percentage than reported in randomized clinical trials. PMID- 22300779 TI - Coincidence of apical ballooning syndrome (tako-tsubo/stress cardiomyopathy) and posterior reversible encephalopathy syndrome: potential common substrate and pathophysiology? AB - BACKGROUND: Apical ballooning syndrome (ABS) and posterior reversible encephalopathy syndrome (PRES) are recently described, seemingly unrelated, reversible conditions. The precise pathophysiology of these syndromes remains unknown. The aim of this study was to describe the clinical characteristics and outcomes of a unique series of patients with both ABS and PRES. METHODS AND RESULTS: In a retrospective study of 224 consecutive patients diagnosed with ABS between 2002 and 2010, 6 (2.7%) were also diagnosed with PRES. All were female with a mean age of 63.7 +/- 12.5 years. All patients had preceding medical comorbidities and physical stress triggers that precipitated ABS and PRES. Mean peak troponin T levels and left ventricular ejection fraction at presentation were 0.47 +/- 0.48 mg/dL and 31.5 +/- 8.2%, respectively. Characteristic left ventricular wall motion abnormalities (regional wall motion score index 2.22 +/- 0.37) were noted in all patients, and magnetic resonance imaging of the brain was significant for vasogenic edema, predominantly in the posterior circulation. All patients recovered left ventricular (ejection fraction at follow-up 60.2 +/- 6.0%) and neurologic function with supportive management. Two patients had recurrence of ABS and 1 of PRES during follow-up. CONCLUSIONS: ABS and PRES can occur simultaneously during an acute illness. Patients with ABS who develop neurologic dysfunction should be evaluated for PRES and vice versa. Because transient sympathetic overactivity and microvascular dysfunction have been observed in both reversible syndromes, we speculate that they may represent the shared pathophysiologic mechanism. PMID- 22300780 TI - High-intensity interval exercise in chronic heart failure: protocol optimization. AB - BACKGROUND: There are little data on the optimization of high-intensity aerobic interval exercise (HIIE) protocols in patients with chronic heart failure (CHF). Therefore, we compared acute cardiopulmonary responses to 4 different HIIE protocols to identify the optimal one. METHODS AND RESULTS: Twenty men with stable systolic CHF performed 4 different randomly ordered single HIIE sessions with measurement of gas exchange. For all protocols (A, B, C, and D) exercise intensity was set at 100% of peak power output (PPO). Interval duration was 30 seconds (A and B) or 90 seconds (C and D), and recovery was passive (A and C) or active (50% of PPO in B and D). Time spent above 85% of VO(2peak) and time above the ventilatory threshold were similar across all 4 HIIE protocols. Total exercise time was significantly longer in protocols with passive recovery intervals (A: 1,651 +/- 347 s; C: 1,574 +/- 382 s) compared with protocols with active recovery intervals (B: 986 +/- 542 s; D: 961 +/- 556 s). All protocols appeared to be safe, with exercise tolerance being superior during protocol A. CONCLUSION: Among the 4 HIIE protocols tested, protocol A with short intervals and passive recovery appeared to be superior. PMID- 22300781 TI - Impact of ventricular dyssynchrony on postexercise accommodation of systolic myocardial motion in hypertensive patients with heart failure and a normal ejection fraction: a tissue-Doppler echocardiography study. AB - BACKGROUND: We hypothesized left ventricular (LV) dyssynchrony would affect postexercise accommodation of regional myocardial motion in patients with heart failure and a normal ejection fraction (HFNEF). METHODS AND RESULTS: Tissue Doppler echocardiography was studied in 100 hypertensive patients with LV ejection fraction >50%. Among them, 70 HFNEF patients were classified into the systolic dyssynchrony (Dys: >65 ms difference of electromechanical delay between septal and lateral segments) (43 patients) and nondyssynchrony (Ndys: 27 patients) groups, and the other 30 patients were as the control (Ctrl). The systolic myocardial velocities (Sm) of 6-basal LV segments at baseline and after exercise were analyzed. When compared with the Ctrl group, the baseline lower mean Sm of 6 LV segments in the Ndys group could increase to a similar postexercise level as that in the Ctrl group, whereas that in the Dys group remained lower after exercise (7.8 +/- 1.3 versus Ndys: 8.6 +/- 1.5 and Ctrl: 8.9 +/- 1.2 cm/s, P < .05, respectively). This is mainly due to a much higher percentage increase of lateral Sm after exercise in the Ndys group (Ndys: 49 versus Dys: 29%, P < .05). CONCLUSIONS: Dyssynchrony-related regional myocardial contractile abnormality after exercise in HFNEF patients suggested the detrimental impact of electromechanical uncoupling on HF symptoms. PMID- 22300782 TI - Survival benefit of implantable cardioverter-defibrillators in left ventricular assist device-supported heart failure patients. AB - BACKGROUND: Implantable cardioverter-defibrillators (ICDs) reduce mortality in heart failure (HF). In patients requiring a ventricular assist device (VAD), the benefit from ICD therapy is not well established. The aim of this study was to define the impact of ICD on outcomes in VAD-supported patients. METHODS AND RESULTS: We reviewed data for consecutive adult HF patients receiving VAD as a bridge to transplantation from 1996 to 2003. The primary outcome was survival to transplantation. A total of 144 VADs were implanted [85 left ventricular (LVAD), 59 biventricular (BIVAD), mean age 50 +/- 12 years, 77% male, left ventricular ejection fraction 18 +/- 9%, 54% ischemic]. Mean length of support was 119 days (range 1-670); 103 patients (72%) survived to transplantation. Forty-five patients had an ICD (33 LVAD, 12 BIVAD). More LVAD patients had an appropriate ICD shock before implantation than after (16 vs 7; P = .02). There was a trend toward higher shock frequency before LVAD implant than after (3.3 +/- 5.2 vs 1.1 +/- 3.8 shocks/y; P = .06). Mean time to first shock after VAD implant was 129 +/ 109 days. LVAD-supported patients with an ICD were significantly more likely to survive to transplantation [1-y actuarial survival to transplantation: LVAD: 91% with ICD vs 57% without ICD (log-rank P = .01); BIVAD: 54% vs 47% (log-rank P = NS)]. An ICD was associated with significantly increased survival in a multivariate model controlling for confounding variables (odds ratio 2.54, 95% confidence interval 1.04-6.21; P = .04). CONCLUSIONS: Shock frequency decreases after VAD implantation, likely owing to ventricular unloading, but appropriate ICD shocks still occur in 21% of patients. An ICD is associated with improved survival in LVAD-supported HF patients. PMID- 22300783 TI - Progressive rise in red cell distribution width is associated with disease progression in ambulatory patients with chronic heart failure. AB - BACKGROUND: Single red cell distribution width (RDW) assessment is a consistent prognostic marker of poor outcomes in heart failure as well as in other patient cohorts. The objective of this study was to determine the prognostic value of sequential RDW assessment in ambulatory patients with chronic heart failure. METHODS AND RESULTS: We reviewed 6,159 consecutive ambulatory patients with chronic heart failure between 2001-2006 and examined changes in RDW values from baseline to 1-year follow-up. Clinical, demographic, laboratory, and ICD-9 coding data were extracted from electronic health records, and all-cause mortality was followed over a mean follow-up of 4.4 +/- 2.4 years. In this study cohort, median baseline RDW was 14.9%. RDW >16% at baseline (18.5% of cohort) was associated with a higher mortality rates than RDW <=16%. For each +1% increment of baseline RDW, the risk ratio for all-cause mortality was 1.17 (95% confidence interval [CI] 1.15-1.19; P < .0001). At 12-month follow-up (n = 1,601), a large majority of subjects (68% in first tertile, 56% in second tertile of baseline RDW) showed rising RDW and correspondingly higher risk for all-cause mortality (risk ratio for +1% increase in changes in RDW was 1.08 (95% CI 1.03-1.13; P = .001). This effect was independent of anemia status or other baseline cardiac or renal indices, and particularly strong in those with lower baseline RDW. CONCLUSIONS: In our ambulatory cohort of patients with chronic heart failure, baseline and serial increases in RDW were associated with poor long-term outcomes independently from standard cardiac, hematologic, and renal indices. PMID- 22300784 TI - Cardiac resynchronization therapy in the real world: comparison with the COMPANION study. AB - BACKGROUND: Several clinical trials have confirmed that cardiac resynchronization therapy (CRT) improves outcomes in well defined patient populations. It is uncertain, however, whether outcomes are similar in real-world clinical settings. This study compared outcomes after CRT with defibrillator (CRT-D) in a large real world private-practice cardiology setting with those in the COMPANION multicenter trial. METHODS AND RESULTS: A total of 429 consecutive patients who received CRT D for standard indications (group 1) were retrospectively compared with the 595 patients (group 3) in the COMPANION CRT-D cohort regarding survival and survival free of cardiovascular (CV) hospitalization. A subgroup of the group 1 patients who met the COMPANION entrance criteria (group 2) was also compared with the COMPANION cohort (group 3) both with and without propensity-matching statistical analysis. Survival and survival free of CV hospitalization was better in group 1 than in group 3. Survival in group 2 with and without propensity matching was similar to group 3. However, survival free of CV hospitalization was better in the real-world patients (group 2) even after adjustment for differences in baseline characteristics. CONCLUSIONS: Survival and CV hospitalization outcomes in a real-world clinical setting are as good as, or better than, those demonstrated in the COMPANION research trial. PMID- 22300785 TI - Echocardiographic evaluation of left ventricular structure and function: new modalities and potential applications in clinical trials. AB - Advances in modern echocardiography for quantification of cardiac structure and function have not been translated in clinical trial or practice applications to date. Imaging endpoints are especially well-suited for early trials with investigational therapies for heart failure as most drugs and devices approved for heart failure have shown favorable effects on cardiac structure and function also. Echocardiography is versatile and can be performed in most clinical settings. The modest interobserver and test-retest reproducibility of specific structural and functional parameters with conventional echocardiography can be improved on by using contemporary modalities, including 3-dimensional (3D) echocardiography for assessment of volumes and ejection fraction and speckle tracking for detailed functional assessment of the ventricles with mechanics based parameters (strain and strain rate). The appropriate imaging endpoints (global vs. regional, systolic vs. diastolic) should be tailored to the specific research question and the mode of action of the therapy under investigation. The newer echocardiographic modalities, namely 3D echocardiography and speckle tracking, are more demanding in terms of equipment and personnel and therefore are better suited for implementation in experienced research centers with central interpretation. However, these modalities provide the best opportunity currently available to demonstrate treatment effects on the myocardium with investigational therapies and provide mechanistic insights for future directions. PMID- 22300786 TI - Characterization and biological function analysis of the trim3a gene from zebrafish (Danio rerio). AB - The biological significance of tripartite motif (TRIM) proteins is increasingly being appreciated due to their roles in a broad range of biological processes that associated with innate immunity. In this study, we have described the structural and functional analysis of TRIM3a from zebrafish. Annotation of domain architectures found that the TRIM3a fulfills the TRIM-NHL rule of domain composition with a Filamin/ABP280 domain and NHL repeats at its C-terminal region. In addition, the mRNA expression level of TRIM3a was the highest in brain, and with a relatively higher level in spleen, liver, and gill. A strong expression starting at 36 h post fertilization (hpf) was observed by real-time PCR and could be detected in brain by in situ hybridization, suggesting that TRIM3a protein might play an important role in brain development in zebrafish. Considering that TRIM3a has a RING finger domain, we expressed and purified the TRIM3a protein and performed ubiquitylation assays, our results showed that TRIM3a underwent self-polyubiquitylation in combination with E1, UbcH5c, biotin ubiquitin in vitro. Meanwhile, TRIM3a-R without the RING domain was expressed and purified as well, in vitro ubiquitylation assays showed that the self ubiquitylation of TRIM3a was dependent on its RING domain, suggesting that TRIM3a might function as a RING finger E3 ubiquitin ligase. PMID- 22300787 TI - A teleostean angiotensinogen from Oplegnathus fasciatus responses to immune and injury challenges. AB - Angiotensinogen (AGT) is the precursor of the renin-angiotensin system and contributes to osmoregulation, acute-phase and immune responses. A full-length cDNA of the AGT (2004 bp with a 1389 bp coding region) was isolated from rock bream (Rb), Oplegnathus fasciatus. The encoded polypeptide of 463 amino acids had a predicted molecular mass of 51.6 kDa. RbAGT possessed a deduced signal peptide of 22 residues upstream of a putative angiotensin I sequence ((23)NRVYVHPFHL(32)). RbAGT possessed a specific domain profile and a signature motif which are characteristics of the serpin family. Sequence homology and phylogenetic analysis indicated that RbAGT was evolutionarily closest to AGT of Rhabdosargus sarba. The mRNA expression profile of RbAGT was determined by quantitative RT-PCR and it demonstrated a constitutive and tissue-specific expression with the highest transcript level in the liver. Significantly up regulated RbAGT expression was elicited by systemic injection of a lipopolysaccharide, rock bream iridovirus (RBIV) and bacteria (Edwardsiella tarda and Streptococcus iniae), revealing its pathogen inducibility. RbAGT manifested a down-regulated response to systemic injury, contemporaneously with two other serpins, protease nexin-1 (PN-1), and heparin cofactor II (HCII). In addition, a synchronized expression pattern was elicited by RbAGT and RbTNF-alpha in response to injury, suggesting that TNF-alpha might be a potential modulator of AGT transcription. PMID- 22300788 TI - Differentiation of follicular cells in polytrophic ovaries of Neuroptera (Insecta: Holometabola). AB - Mechanisms that underlie differentiation and diversification of the ovarian follicular epithelium in insects have been best characterized in a fruit fly, Drosophila melanogaster. Recent comparative analyses have shown that dipterans evolved a common, specific system of early patterning of their follicular epithelium, while some of the follicular cells acquired an ability to undertake active and invasive migrations. To gain insight into the evolution of the differentiation pathways we extended comparative analyses to Neuroptera, one of the most archaic holometabolan insects with polytrophic ovaries. Here, we show that the follicular cell differentiation pathway in neuropteran ovaries significantly differs from that observed in Drosophila and its relatives. In neuropteran ovaries differentiation of the germ line cells precedes the organization of the follicular epithelium. In consequence, at early stages of egg chamber formation germ cell clusters are not enveloped completely by the regular follicular epithelium but associate with two types of somatic cells: interstitial and prefollicular cells. Interstitial cells do not contribute to the formation of the follicular epithelium, while prefollicular cells diversify into a number of follicular cell subgroups. Some follicular cells remain in contact with the nurse cell compartment. The remaining ones associate with the lateral aspects of the oocyte and diversify into the mainbody follicular cells and the anterior and posterior centripetal cells. In the advanced stages of vitellogenesis protrusions of the anterior and posterior centripetal cells penetrate the nurse cell-oocyte interface and dragging behind their neighboring mainbody cells, eventually encapsulate the oocyte pole(s) with a confluent epithelial layer. The follicular cells in neuropteran ovaries are not migratory at all. They may only change their position relative to the germ line cells. Almost complete immobility of follicular cells in neuropteran egg chambers results in a lower number of diversified subpopulations when compared to Drosophila and other true flies. PMID- 22300789 TI - mGluR3 and not mGluR2 receptors mediate the efficacy of NAAG peptidase inhibitor in validated model of schizophrenia. PMID- 22300790 TI - Surgical results of arachnoid-preserving posterior fossa decompression for Chiari I malformation with associated syringomyelia. AB - We analyzed the outcome of posterior fossa decompression accompanied by widening of the cisterna magna, without disturbing the arachnoid, in patients with Chiari I malformation (CMI) associated with syringomyelia. Twenty-five adult patients with CMI and syringomyelia, who underwent surgery between October 2000 and December 2008, were enrolled in this study. All patients underwent foramen magnum decompression with C1 decompression, with or without C2 decompression. Three surgeons performed a dura opening with duraplasty in 20 patients, and another surgeon excised the outer layer of the dura without duraplasty in five patients. Clinical and radiological assessments were performed preoperatively and during the follow-up period. After surgery, 20 (80%) patients achieved a significant improvement in their clinical symptoms. However, four patients (16%) achieved only a stable state, and one patient's symptoms worsened. Radiological analysis showed that 17 patients (68%) had a favorable result; that is, a total collapse, or a marked reduction, of the syrinx. Seven patients (28%) were stable in terms of syrinx size. However, the syrinx enlarged in one patient who had undergone excision of the outer dura. Twenty-four patients achieved a widened cisterna magna with ascent of the cerebellar tonsils into the posterior fossa and acquisition of a more rounded shape. Postoperative complications included a transient headache and vomiting in three patients and transient motor weakness in one patient. Two patients developed a superficial wound infection. This study shows that arachnoid-preserving posterior fossa decompression is a safe and effective treatment for patients with CMI with associated syringomyelia. PMID- 22300791 TI - The effect of ischemic post-conditioning on hippocampal cell apoptosis following global brain ischemia in rats. AB - We evaluated the effect of brain ischemic post-conditioning on cell apoptosis in the hippocampus following global brain ischemia in rats. Adult male Sprague Dawley rats were randomly divided into three groups (n=15/group): sham operation, ischemia/reperfusion (I/R) and ischemic post-conditioning (I PostC). Global brain ischemia was induced by four-vessel occlusion. Ischemic post-conditioning consisted of six cycles of 10s/10s reperfusion/reocclusion at the onset of reperfusion. All rats were sacrificed 24 hours or 72 hours after reperfusion. The hippocampal CA1 regions were analysed using the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end-labelling (Tunel) staining technique for determining cell apoptosis. Levels of caspase-3 and Bcl-2 were measured by Western blotting. After 72 hours, fewer Tunel-positive brain cells were observed in rats from the I PostC group than in rats from the I/R group (10.3 +/- 2.7% versus 40.8 +/- 6.2%, p<0.01). After reperfusion at 24 hours and 72 hours, expression of caspase-3 in the I PostC group was significantly decreased (p<0.01) and expression of Bcl-2 in the I PostC group was significantly increased (p<0.01) compared with the I/R group. We conclude that down-regulation of caspase-3 and up-regulation of Bcl-2 by ischemic post conditioning may underlie the protective effects of post-conditioning. PMID- 22300792 TI - Downregulation of PCDH9 predicts prognosis for patients with glioma. AB - Recent evidence has indicated that biological markers are essential in estimating the prognosis of patients with gliomas. The aim of this study was to determine the status and clinical significance of a novel tumor suppressor, PCDH9 (protocadherin 9) in glioma using tissue microarrays and immunohistochemistry. Normal brain tissue showed strong positive immunostaining for PCDH9, but this was downregulated in the primary cerebral glial tumor samples (51.7%). Loss of PCDH9 expression was associated significantly with a higher histological grade. Survival analysis demonstrated that patients with PCDH9-negative tumors had significantly shorter survival times than those with PCDH9-positive tumors and that PCDH9 was an independent prognostic factor. Our results suggest that PCDH9 might function as a tumor suppressor during cancer development and progression and could be regarded as a useful biomarker for predicting the outcome of patients with cerebral glial tumors. PMID- 22300793 TI - A rare brainstem hemorrhage during transvenous embolization of a cavernous dural arteriovenous fistula. AB - Intravascular treatment of cavernous dural arteriovenous fistula (dAVF) is usually safe and effective. However, we describe a patient with a rare brainstem hemorrhage during transvenous embolization (TVE). A 79-year-old woman suffered from left chemosis and diplopia. Cerebral angiography revealed a left cavernous dAVF with cortical venous drainage. The patient underwent TVE of the cavernous sinus (CS) via the left inferior petrosal sinus. Superior petrosal sinus (SPS) outflow occlusion was performed to avoid venous congestion, followed by superficial middle cerebral vein outflow occlusion, selective shunt occlusion of the middle meningeal artery, and superior orbital vein outflow occlusion. The patient's condition suddenly deteriorated during CS packing. A CT scan revealed a massive brainstem hemorrhage. Cerebral angiography did not show SPS reopening or redistributed drainage to the posterior fossa. Thus, TVE for cavernous dAVF can result in life-threatening vascular complications. Well-planned treatment strategies could avert this rare complication. PMID- 22300794 TI - Morphology of preimaginal stages of Calliphora vicina Robineau-Desvoidy, 1830 (Diptera, Calliphoridae): a comparative study. AB - A comparative morphological study of preimaginal stages (larvae and pupae) of Calliphora vicina Robineau-Desvoidy, 1830 is presented. The entomological samples came from laboratory colonies bred under controlled environmental conditions (25 degrees C and 60% relative humidity). In this study, a recently published technique to clear Diptera larvae for light microscopy and a standard protocol for scanning electron microscopy were used. For the morphological comparison of larval instars I, II and III, and pupae of C. vicina, different larval regions (cephalic, thoracic and abdominal, including anal division), as well the internal chitinised cephalopharyngeal skeleton, were considered separately. Our results focus on showing the changes observed throughout development for the most important structures in the cephalic region (sensilla of maxillary palpus, antennae and oral ridges), the thoracic region (the first segment and its anterior spinose band) and in the anal division of the abdominal region (posterior spiracles and shape of the papillae). In addition, some morphological structures are described or pictured for the first time, such as the ventral organ and the anterior spiracle of larva I and the antenna sensilla, Keilin's organ and wrinkled area of the anal division of all instars. The cephalopharyngeal skeleton is an important structure for the taxonomy of Diptera larvae in all instars, including Calliphoridae. Our observations in C. vicina indicate that an in-depth review of the sclerite composition is needed. Pupae and larvae stages can only be compared by following the segmentary spinose bands and the anal segment, where the morphology of the posterior spiracles and papillae can be observed, in some cases despite the reduced condition of the latter. PMID- 22300795 TI - Quantitative analysis of methamphetamine in hair of children removed from clandestine laboratories--evidence of passive exposure? AB - In New Zealand many children have been removed from clandestine laboratories following Police intervention. In the last few years it has become standard procedure that these children have hair samples taken and these samples are submitted to the laboratory for analysis. There are various mechanisms for the incorporation of drugs into hair. The hair follicle has a rich blood supply, so any drug that may be circulating in the blood can be incorporated into the growing hair. Another mechanism is via external contamination, such as spilling a drug on the hair or through exposure to fumes or vapours. Hair samples were analysed for methamphetamine and amphetamine. From the 52 cases analysed 38 (73%) were positive for methamphetamine (>0.1 ng/mg) and amphetamine was detected in 34 of these cases. In no case was amphetamine detected without methamphetamine. The hair washes (prior to extraction) were also analysed (quantified in 30 of the positive cases) and only 3 had a wash to hair ratio of >0.1 (all were <0.5), which may be indicative of a low level of external contamination. This low level of evidence of external contamination suggests that the children are exposed to methamphetamine and are incorporating it into the hair through the blood stream. PMID- 22300796 TI - The first international proficiency test on ketamine and norketamine in hair. AB - This paper discusses the organization of the first international proficiency test (PT) programme on ketamine (K) and norketamine (NK) in hair samples. The primary objective of the programme was to evaluate the analytical capability of participating laboratories on hair analysis for K and NK via comparison of results. Authentic samples, instead of spiked samples were used in the programme to mimic the analysis of incorporated illicit drugs in real-life situations. Eight of the ten participating medical or forensic laboratories from Australia, France, Hong Kong, Italy, Singapore and the USA returned results to the organizer. Quantification methods from these laboratories were confined to GC-MS and LC-MS/MS. Performance assessment based on z-score indicated that only three laboratories achieved satisfactory results for both the analysis of K and NK. It was concluded that the overall performance of the participating laboratories was fair and there is still room for further improvement. Additional similarly designed PT programmes are recommended to be organized in order to encourage reliable measurements of illicit drugs in hair samples. Taking into account the substantial effect on the consensus values within limited number of data points, a recommendation on the provision of reference values assigned by accurate methods will be of benefit to small size PT programmes in the forensic field. PMID- 22300797 TI - A heuristic approach to RNA-RNA interaction prediction. AB - RNA-RNA interaction is used in many biological processes such as gene expression regulation. In this process, an RNA molecule prohibits the translation of another RNA molecule by establishing stable interactions with it. In this regard, some algorithms have been formed to predict the structure of the interaction between two RNA molecules. One common pitfall in the most algorithms is their high computational time. In this paper, we introduce a novel algorithm called TIRNA to accurately predict the secondary structure between two RNA molecules based on minimum free energy (MFE). The algorithm is stand on a heuristic approach which employs some dot matrices for finding the secondary structure of each RNA and between two RNAs. The proposed algorithm has been performed on some standard datasets such as CopA-CopT, R1inv-R2inv, Tar-Tar*, DIS-DIS and IncRNA54-RepZ in the Escherichia coli bacteria. The time and space complexity of the algorithm are 0(k2 log k2) and 0(k2), respectively, where k indicates the sum of the length of two RNAs. The experimental results show the high validity and efficiency of the TIRNA. PMID- 22300798 TI - Economic analysis of the use of facemasks during pandemic (H1N1) 2009. AB - A large-scale pandemic could cause severe health, social, and economic impacts. The recent 2009 H1N1 pandemic confirmed the need for mitigation strategies that are cost-effective and easy to implement. Typically, in the early stages of a pandemic, as seen with pandemic (H1N1) 2009, vaccines and antivirals may be limited or non-existent, resulting in the need for non-pharmaceutical strategies to reduce the spread of disease and the economic impact. We construct and analyze a mathematical model for a population comprised of three different age groups and assume that some individuals wear facemasks. We then quantify the impact facemasks could have had on the spread of pandemic (H1N1) 2009 and examine their cost effectiveness. Our analyses show that an unmitigated pandemic could result in losses of nearly $832 billion in the United States during the length of the pandemic. Based on present value of future earnings, hospital costs, and lost income estimates due to illness, this study estimates that the use of facemasks by 10%, 25%, and 50% of the population could reduce economic losses by $478 billion, $570 billion, and $573 billion, respectively. The results show that facemasks can significantly reduce the number of influenza cases as well as the economic losses due to a pandemic. PMID- 22300799 TI - Impact of endothelium roughness on blood flow. AB - Cell free layer (CFL), a plasma layer bounded by the red blood cell (RBC) core and the endothelium, plays an important physiological role. Its width affects the effective blood viscosity as well as the scavenging and production of nitric oxide (NO). Measurements of the CFL and its spatio-temporal variability are highly uncertain, exhibiting random fluctuations. Yet traditional models of blood flow and NO scavenging treat the CFL's bounding surfaces as deterministic and smooth. We investigate the effects of the endothelium roughness and uncertain (random) spatial variability on blood flow and the estimates of effective blood viscosity. PMID- 22300800 TI - The limitations of scaling laws in the prediction of performance in endurance events. AB - In the twentieth century, scientists have examined running speed over various distances, analyzing world records and studying the ability of an athlete to sustain a given speed. Assuming that running speed expresses the response of a non-linear multisystemic behavior, the relationship between these two variables (distance vs. velocity) can therefore be evaluated by applying scaling laws that fulfill the key principles of specificity and individuality of each athlete, yet responding to bioenergetic and functional patterns that are well-known to sports physiology. Since speed loss as distance increases exhibits fractal behavior, with small changes in the speed-reduction curve due to the effect of fatigue, it must be recognized that no universal scaling law can account, with acceptable precision, for the effect exerted by fatigue on potential speed at any given moment in a race. Power laws using a range of scaling exponents provide technical staff and athletes with a reliable, non-invasive tool for planning of training schedules, predicting athletes' performances over various distances and comparing the performance of specialists in different track events. The equations for the scaling laws for the distances investigated here were: V1500=15.00 * D-0.10 (R2=0.99); V3000=12.76 * D-0.08 (R2=0.99); V5000=11.55 * D-0.07 (R2=0.99); V10,000=11.59 * D-0.07 (R2=0.99); V21,095=10.78 * D-0.06 (R2=0.97); V42,175=10.27 * D-0.057 (R2=0.99). PMID- 22300801 TI - Characterization of micro- and nanophase separation of dentin bonding agents by stereoscopy and atomic force microscopy. AB - The aim was to study the effect of solvents on the phase separation of four commercial dental adhesives. Four materials were tested: ClearfilTM SE Bond (CSE), Clearfil Protect Bond (CPB), Clearfil S3 Bond (CS3), and One-Up Bond F Plus (OUB). Distilled water or ethanol was used as a solvent (30 vol%) for microphase separation studies, by stereoscopy. For nanophase images, the mixtures were formulated with two different solvent concentrations (2.5 versus 5 vol%) and observed by atomic force microscopy. Images were analyzed by using MacBiophotonics ImageJ to measure the area of bright domains. Macrophase separations, identified as a loss of clarity, were only observed after mixing the adhesives with water. Nanophase separations were detected with all adhesive combinations. The area of bright domains ranged from 132 to 1,145 nm2 for CSE, from 15 to 285 nm2 for CPB, from 149 to 380 nm2 for CS3, and from 26 to 157 nm2 for OUB. In water-resins mixtures, CPB was the most homogeneous and OUB showed the most heterogeneous phase formation. In ethanol-resin mixtures, CSE attained the most homogeneous structure and OUB showed the most heterogeneous phase. Addition of 5 vol% ethanol to resins decreased the nanophase separation when compared with the control materials. PMID- 22300802 TI - The attenuation of microorganisms in on-site wastewater effluent discharged into highly permeable subsoils. AB - An extensive field study on percolation areas receiving both septic tank and secondary treated on-site effluents from single houses in Ireland was carried out to investigate the attenuation capacity of highly permeable subsoils with respect to E. coli bacteria and spiked bacteriophages (MS2, PhiX174 and PR772). The development of biomats across the percolation areas receiving the secondary effluent was restricted compared to the percolation area receiving septic tank effluent, promoting a much higher areal hydraulic loading which created significant differences in the potential microbiological loading to groundwater. Greatest E. coli removal in the subsoil occurred within the first 0.35 m of unsaturated subsoil for all effluent types. Analysis showed, however, that more evidence of faecal contamination occurred at depth in the subsoils receiving secondary treated effluents than that receiving septic tank effluent, despite the lower bacterial influent load. All three bacteriophages were reduced to their minimum detection limit (<10 PFU/mL) at a depth of 0.95 m below the percolation trenches receiving septic tank effluent, although isolated incidences of PhiX174 and PR772 were measured below one trench. However again, slightly higher breakthroughs of MS2 and PR772 contamination were detected at the same depth under the trenches receiving secondary treated effluent. PMID- 22300803 TI - Molecular structure refinement by direct fitting of atomic coordinates to experimental ESR spectra. AB - An attempt is made to bypass spectral analysis and fit internal coordinates of radicals directly to experimental liquid- and solid-state electron spin resonance (ESR) spectra. We take advantage of the recently introduced large-scale spin dynamics simulation algorithms and of the fact that the accuracy of quantum mechanical calculations of ESR parameters has improved to the point of quantitative correctness. Partial solutions are offered to the local minimum problem in spectral fitting and to the problem of spin interaction parameters (hyperfine couplings, chemical shifts, etc.) being very sensitive to vibrational excursions from the equilibrium geometry. PMID- 22300804 TI - Control of HBV replication by antiviral microRNAs transferred by lentiviral vectors for potential cell and gene therapy approaches. AB - BACKGROUND: Because molecular mechanisms regulating host cell and virus interactions are not fully understood, we further defined roles of antiviral microRNAs (miRNAs) in HBV replication. METHODS: We studied small interfering RNA sequences inserted into the miR-30 backbone in cell systems. Antiviral sequences were cloned into lentiviral vectors upstream of a green fluorescent protein reporter. Transduced cells included HepG2 or HepG2 2.2.15 cell lines and hTERT-FH B fetal human liver cells. HBV replication was analysed by several assays. RESULTS: In 2.2.15 cells treated with constructs primarily targeting HBV polymerase and surface antigen or HBV polymerase and X open reading frames, HBV core protein, HBV DNA and HBV RNA expression decreased. This antiviral effect was more pronounced when the two constructs were expressed together. Similarly, antiviral constructs decreased HBV replication in HepG2 cells transduced with adenoviral vector to express HBV. Although antiviral sequences were expressed in hTERT-FH-B cells, these cells were non-permissive for HBV, possibly owing to expression of miRNAs reported to inhibit HBV replication, whereas these miRNAs were absent in HepG2 cells. Expression of antiviral miRNAs did not affect cell viability or proliferation and no deleterious changes were observed in expression of native cellular miRNAs. Moreover, expression of antiviral miRNA did not affect engraftment and survival of transplanted cells in mice. CONCLUSIONS: Identification of effective antiviral miRNAs and transfer of suitable constructs by lentiviral vectors will be helpful for pathophysiological studies of host cell virus interactions. Simultaneously, this will advance potential mechanisms for cell/gene therapy in those afflicted with chronic hepatitis and refractory liver disease. PMID- 22300805 TI - Parasite-specific aptamers as biosynthetic reagents and potential pharmaceuticals. AB - Aptamers are short, synthetic nucleic acid molecules. They are generated by a Darwinian-type in vitro evolution method known as 'systematic evolution of ligands by exponential enrichment' (SELEX). SELEX represents an experimental platform to identify rare ligands with predetermined functionality from combinatorial nucleic acid libraries. Since its discovery about 20 years ago the method has been instrumental in identifying a large number of aptamers that recognize targets of very different chemistry and molecular complexity. Although aptamers have been converted into sophisticated biomolecular tools for a diverse set of technologies, only a limited number of aptamers have been selected as binding reagents for parasites or parasite-derived molecules. Here the published examples of aptamers that target Leishmania-, Trypanosoma- and Plasmodia-specific molecules are reviewed. PMID- 22300806 TI - Feeding strategies of anthropophilic mosquitoes result in increased risk of pathogen transmission. AB - Vector-borne disease specialists have traditionally assumed that in each egg laying cycle mosquitoes take a single bloodmeal that is used for egg development and feed on plant sugars for flight and production of energy reserves. Here we review research showing that for two of the most important vectors of human pathogens (Anopheles gambiae and Aedes aegypti) imbibing multiple bloodmeals during a gonotrophic cycle while foregoing sugar feeding is a common behaviour, not an exception. By feeding preferentially and frequently on human blood these species increase their fitness and exponentially boost the basic reproduction rate of pathogens they transmit. Although the epidemiological outcome is similar, there are important differences in processes underlying frequent human contact by these species that merit more detailed investigation. PMID- 22300807 TI - Malaria's deadly secret: a skin stage. AB - The role skin plays in malaria infection has long been overlooked. Recent analysis, however, suggests skin-infecting sporozoites initiate rapid suppression of immunity, establishing early tolerance to subsequent lifecycle stages. This explains susceptibility to reinfection by mosquito bite, independent of blood stage-induced immunosuppression or semi-immunity. Vaccine trials corroborate skin initiated immunosubversion due to skin-infecting forms, tightly correlating bite pre-exposure, live parasites in the skin and endemic vaccine failure. Rapidly advancing skin immunobiology and recently described parasite development in host skin further substantiate the proposed model, consolidating a new concept in parasite biology, exemplified by malaria: natural infection has a defined, potently immunosubversive skin stage, crucially affecting vaccine function and vitally relevant to eradication. PMID- 22300808 TI - The accuracy of ultrasonography in the preoperative diagnosis of cervical lymph node (LN) metastasis in patients with papillary thyroid carcinoma: A meta analysis. PMID- 22300809 TI - Magnetic resonance as an alternative imaging method for the evaluation of patients with pulmonary hypertension. PMID- 22300811 TI - Distinct neural networks underlie encoding of categorical versus coordinate spatial relations during active navigation. AB - It has been proposed that spatial relations are encoded either categorically, such that the relative positions of objects are defined in prepositional terms; or in terms of visual coordinates, such that the precise distances between objects are represented. In humans, it has been assumed that a left hemisphere neural network subserves categorical representations, and that coordinate representations are right lateralised. However, evidence in support of this distinction has been garnered exclusively from tasks that involved static, two dimensional (2D) arrays. We used functional magnetic resonance imaging (fMRI) to identify neural circuits underlying categorical and coordinate representations during active spatial navigation. Activity in the categorical condition was significantly greater in the parietal cortex, whereas the coordinate condition revealed greater activity in medial temporal cortex and dorsal striatum. In addition, activity in the categorical condition was greater in parietal cortex within the left hemisphere than within the right. Our findings are consistent with analogous studies in rodents, and support the suggestion of distinct neural circuits underlying categorical and coordinate representations during active spatial navigation. The findings also support the claim of a left hemispheric preponderance for the processing of categorical spatial relations. PMID- 22300812 TI - Functional activity of the right temporo-parietal junction and of the medial prefrontal cortex associated with true and false belief reasoning. AB - Since false belief reasoning requires mental state representation independently of the state of reality, it is seen as a key ability in Theory of Mind (ToM). Although true beliefs do not have to be processed independently of the state of reality, growing behavioural evidence indicates that true belief reasoning is different from just reasoning about the state of reality. So far, neural studies on true and false belief reasoning revealed inconsistent findings in the medial prefrontal cortex (MPFC) and in the right temporo-parietal junction (R-TPJ), brain regions that are hypothesized to play an important role in ToM. To further explore true and false belief reasoning, the present functional magnetic resonance imaging (fMRI) study in eighteen adult subjects used methodological refinements such as ensuring that the true belief trials did not elicit false belief reasoning, as well as including paralleled control conditions requiring reasoning about the state of reality. When compared to its control condition, common R-TPJ activity was observed for true and false belief reasoning, supporting its role in belief reasoning in general, and indicating that, at least in adults, also true belief reasoning appears to be different from reasoning about the state of reality. Differential activity was observed in a broad network of brain regions such as the MPFC, the inferior frontal cortex, and the precuneus. False over true belief reasoning induced activation in the posterior MPFC (pMPFC), supporting its role in the decoupling mechanisms, which is defined as processing a mental state independently of the state of reality. PMID- 22300813 TI - Evidence of a direct influence between the thalamus and hMT+ independent of V1 in the human brain as measured by fMRI. AB - In the present study we employed Conditional Granger Causality (CGC) and Coherence analysis to investigate whether visual motion-related information reaches the human middle temporal complex (hMT+) directly from the Lateral Geniculate Nucleus (LGN) of the thalamus, by-passing the primary visual cortex (V1). Ten healthy human volunteers underwent brain scan examinations by functional magnetic resonance imaging (fMRI) during two optic flow experiments. In addition to the classical LGN-V1-hMT+ pathway, our results showed a significant direct influence of the blood oxygenation level dependent (BOLD) signal recorded in LGN over that in hMT+, not mediated by V1 activity, which strongly supports the existence of a bilateral pathway that connects LGN directly to hMT+ and serves visual motion processing. Furthermore, we evaluated the relative latencies among areas functionally connected in the processing of visual motion. Using LGN as a reference region, hMT+ exhibited a statistically significant earlier peak of activation as compared to V1. In conclusion, our findings suggest the co-existence of an alternative route that directly links LGN to hMT+, bypassing V1. This direct pathway may play a significant functional role for the faster detection of motion and may contribute to explain persistence of unconscious motion detection in individuals with severe destruction of primary visual cortex (blindsight). PMID- 22300814 TI - Epidermogenesis in a skin wound deep through the basement membrane contributes to scar formation. PMID- 22300815 TI - Non-coding RNAs: key regulators of mammalian transcription. AB - Non-coding RNAs (ncRNAs) are now recognized as active participants in controlling many biological processes. Indeed, these products of transcription can even control the process of transcription itself. In the past several years, ncRNAs have been found to regulate transcription of single genes, as well as entire transcriptional programs, affecting the expression of hundreds to thousands of genes in response to developmental or environmental signals. Compared to more classical protein regulators, the list of ncRNAs that regulate mRNA transcription in mammalian cells is still small; however, the rate at which new ncRNA transcriptional regulators are being discovered is rapid, suggesting that models for how gene expression is controlled will continue to be redefined as this field develops. PMID- 22300816 TI - CGH and SNP array using DNA extracted from fixed cytogenetic preparations and long-term refrigerated bone marrow specimens. AB - BACKGROUND: The analysis of nucleic acids is limited by the availability of archival specimens and the quality and amount of the extracted material. Archived cytogenetic preparations are stored in many laboratories and are a potential source of total genomic DNA for array karyotyping and other applications. Array CGH using DNA from fixed cytogenetic preparations has been described, but it is not known whether it can be used for SNP arrays. Diagnostic bone marrow specimens taken during the assessment of hematological malignancies are also a potential source of DNA, but it is generally assumed that DNA must be extracted, or the specimen frozen, within a day or two of collection, to obtain DNA suitable for further analysis. We have assessed DNA extracted from these materials for both SNP array and array CGH. RESULTS: We show that both SNP array and array CGH can be performed on genomic DNA extracted from cytogenetic specimens stored in Carnoy's fixative, and from bone marrow which has been stored unfrozen, at 4 degrees C, for at least 36 days. We describe a procedure for extracting a usable concentration of total genomic DNA from cytogenetic suspensions of low cellularity. CONCLUSIONS: The ability to use these archival specimens for DNA based analysis increases the potential for retrospective genetic analysis of clinical specimens. Fixed cytogenetic preparations and long-term refrigerated bone marrow both provide DNA suitable for array karyotyping, and may be suitable for a wider range of analytical procedures. PMID- 22300817 TI - Shoulder arthroplasty. Part 1: Prosthesis terminology and classification. AB - Shoulder arthroplasty is the third most common joint replacement procedure in the UK, and there are a number of different implant options available to surgeons to treat a variety of shoulder disorders. With an increasing burden placed on clinical follow-up, more patients are remaining under the care of their general practitioners and musculoskeletal triage assessment services and are not necessarily being seen by specialists. Referrals to orthopaedic specialists are therefore often prompted by radiological reports describing evidence of implant failure. This article is the first of two reviews on shoulder arthroplasty, concentrating on implant features and the indications for their use. The second article will address the modes of failure of shoulder arthroplasty and describe the relevant associated radiological features. PMID- 22300818 TI - Medico-legal issues in breast imaging. AB - AIM: To identify medico-legal issues that occur in the diagnosis and radiological management of breast disease and to propose measures to reduce the risk of patient complaints and legal action in breast radiology and diagnosis. MATERIALS AND METHODS: Institutional review board approval was not applicable for this study. A retrospective study was undertaken and records of 120 medico-legal investigations over a 10 year period were examined. The reports were compiled by two consultant breast radiologists. RESULTS: The mean age of the patients represented in this study was 48.3 years. The main complaint in this series was a delay in diagnosis (92%) followed by inappropriate or inadequate treatment (8%). 81% of cases were patients who had presented to the symptomatic clinic. The main presenting symptom was a palpable lump (65%). Substandard care was cited in 49/120 cases (41%). The mean average delay in diagnosis was 15.6 months. Of the cases cited as substandard care, 61% were considered the fault of the radiologist and 14% considered the fault of the breast surgeon. Of the cases where the radiologist was considered to be at fault, microcalcification was the most common mammographic sign to be missed or misinterpreted (12/26 cases, 46%). CONCLUSION: The most common complaint in this series was delay in diagnosis with microcalcification being the main mammographic sign that was either not seen or misinterpreted by the radiologist. Clear and precise written protocols are recommended for all breast imaging practice to ensure that medico-legal investigations will be greatly reduced. PMID- 22300819 TI - Re: Imaging male breast cancer. PMID- 22300820 TI - A proposed new imaging pathway for patients with suspected lung cancer. AB - AIMS: PET-CT scans are routinely performed in patients with lung cancer after investigation by chest x-ray (CXR) and CT scan, when these have demonstrated potentially curable disease. If the majority of patients with lung cancer potentially suitable for curative treatment could be identified earlier in the diagnostic pathway on the basis of CXR findings they could be referred for PET-CT imaging without a prior CT scan. We investigated the clinical and financial implications of adopting such a strategy. MATERIALS AND METHODS: The details of 1187 patients referred with suspected lung cancer between July 2006 and August 2009 were analysed. The initial CXR and subsequent imaging of patients fit for curative treatment (Performance Status 0/1, FEV1 > 1.0) were reviewed (n = 251). The clinical and financial implications of referring patients for first line PET CT if deemed potentially curable based on CXR findings were assessed. RESULTS: 107 of 1187 patients had potentially curable lung cancer on PS, lung function, CT and PET-CT. 96 of these 107 patients (90%) were correctly identified on CXR. 149 patients overall were diagnosed as potentially curable on CXR. Referring suitable patients for an immediate PET-CT scan resulted in a reduction in the time to complete staging investigations. CONCLUSIONS: Early PET-CT scanning for patients with suspected lung cancer, potentially suitable for curative therapy could result in more efficient staging with little additional cost. PMID- 22300821 TI - Value of subtraction MRI in assessing treatment response following image-guided loco-regional therapies for hepatocellular carcinoma. AB - AIM: To compare contrast-enhanced subtraction magnetic resonance imaging (MRI) with contrast-enhanced standard MRI in assessing treatment response following loco-regional therapies for hepatocellular carcinoma (HCC). METHOD AND MATERIALS: Institutional review board approval was obtained and informed consent was waived for this retrospective study. All patients were analysed from our institution's liver tumour database that had loco-regional HCC therapy and the following: (1) a contrast-enhanced MRI <=6 weeks post-treatment, (2) an unenhanced T1-weighted high-signal treatment zone (TZ) >=1 cm, (3) follow-up contrast-enhanced MRI performed >=6 months post-treatment. Randomized standard and subtraction TZ datasets were independently assessed by three blinded radiology readers for either complete treatment necrosis or residual disease. The standard of reference (SOR) comprised a consensus read by two radiologists with knowledge of the follow up MRI and all available clinical data. Statistical analyses were performed using receiver operating characteristics (ROC), t-test, and kappa statistic. RESULTS: Twenty-six patients (19 male and seven female patients; mean age 60 years, standard deviation 10.9 years, range 46-88 years) had a total of 45 corresponding HCCs and TZs. For ROC, the area under the curve (AUC) was 0.93 (subtraction protocol) versus 0.90 (standard protocol; p = 0.49). For the t-test, the mean reader confidence level was 4.4, 3.6, and 4.4 (subtraction protocol) versus 3, 3, and 3.7 (standard protocol; p <= 0.011). The kappa statistic for reader-to-SOR agreement was 0.83, 0.63, and 0.71 (subtraction protocol) versus 0.51, 0.36, and 0.64 (standard protocol). CONCLUSION: Subtraction MRI significantly improves the reader confidence level in the assessment of treatment response following loco regional therapies for HCC. PMID- 22300822 TI - [Evaluation of renal oxygen content by BOLD MRI]. AB - Blood Oxygen Level-Dependent (BOLD) MRI signal is a new method of renal functional imaging which allows renal cortical and medullary oxygen contents measurement in a noninvasive way and without injection of potentially nephrotoxic contrast product. Several clinical and experimental studies showed its potential interest in measuring renal oxygen content and its variation during different renal injuries, allowing new progress in the comprehension of the pathophysiology of several nephropathies. PMID- 22300823 TI - Introduction: The role of the pediatrician in military medicine. PMID- 22300824 TI - Pediatric medical education in the United States military. PMID- 22300825 TI - Early neonatal research at Wilford Hall US Air Force Medical Center. PMID- 22300826 TI - Pediatric infectious diseases: 60 years of contributions by military pediatricians. PMID- 22300827 TI - Military children, families, and communities: supporting those who serve. PMID- 22300828 TI - American pediatricians at war: a legacy of service. PMID- 22300829 TI - Autoantibodies associated with RNA are more enriched than anti-dsDNA antibodies in circulating immune complexes in SLE. AB - To what extent different autoantibodies accumulate in systemic lupus erythematosus (SLE) immune complexes (ICs), and whether such accumulation is associated with disease activity has been investigated. ICs were isolated from SLE sera by both polyethylene glycol (PEG) precipitation and C1q-binding. Autoantibody specificities were determined using a lineblot assay quantified by densitometry. To compare the relative levels of autoantibodies, levels were normalized to the total levels of IgG measured by ELISA in sera and parallel ICs. Samples were investigated both in a cross-sectional design as well as in a paired design with samples obtained during both active and inactive SLE. All investigated autoantibody specificities except anti-dsDNA were enriched in circulating ICs as compared with parallel sera. The group of antibodies against RNA-associated antigens (anti-RNP/Sm, anti-Sm, anti-SSA/Ro60, anti-SSA/Ro52, anti SSB/La) all exhibited higher median enrichment than the DNA-associated (anti dsDNA, anti-histones, anti-nucleosomes) or cytoplasmic (anti-ribosomal P) antigens. In particular autoantibodies against RNP/Sm and SSA/Ro52 had the highest degree of enrichment in SLE PEG precipitates. These findings were corroborated by analysis of autoantibody content in C1q-bound ICs. There was no difference in degree of IC accumulation of the investigated autoantibodies during active and inactive SLE. Our findings demonstrate a difference in enrichment between autoantibodies against RNA- and DNA-associated autoantigens in isolated SLE IC, suggesting that the RNA-associated autoantibodies are more prone to form circulating ICs in SLE, in contrast to antibodies against DNA-associated autoantigens such as dsDNA. These finding have implications in understanding mechanisms of differential autoantibody accumulation in target organs in SLE. PMID- 22300830 TI - Idiopathic intracranial hypertension as a significant cause of intractable headache in patients with systemic lupus erythematosus: a 15-year experience. AB - OBJECTIVE: To evaluate the occurrence of idiopathic intracranial hypertension (IIH) in patients with systemic lupus erythematosus (SLE) and to describe the manifestations, treatments and outcomes in these patients. METHODS: We reviewed the medical records of 1084 patients with SLE followed up from January 1997 to June 2011 in our unit. We identified patients with IIH and analyzed the demographic, clinical and laboratory characteristics of these patients. RESULTS: Among the 1084 SLE patients, 47 underwent cerebrospinal fluid studies because of their intractable headache and eight (17%) of these were diagnosed as IIH. All were females aged 14 to 32 years. Nobody belonged to the obesity group. Headache, nausea, vomiting and blurred vision were the most common presenting symptoms. All patients had active SLE at the time of admission (SLE disease activity index >=6). Five patients had lupus nephritis. In eight patients, there were two with antiphospholipid antibodies, two with anti-ribosomal P antibodies and six with anti-Ro antibodies. All subjects recovered without any complication after high dose steroid therapy. CONCLUSIONS: IIH accounts for a considerable part of the causes of intractable headache in SLE patients and steroids should be considered as a first-line treatment. PMID- 22300831 TI - Production of anti-double-stranded DNA antibodies in activated lymphocyte derived DNA induced lupus model was dependent on CD4+ T cells. AB - Our previous study demonstrated that activated lymphocyte derived DNA (ALD-DNA) could function as an autoantigen to induce production of anti-double-stranded DNA (anti-dsDNA) antibodies in syngeneic BALB/c mice. Here we carefully evaluated the potential role of T cells in the induction of anti-dsDNA antibody. We demonstrated that ALD-DNA could effectively induce production of anti-dsDNA antibodies in vivo and in vitro. In contrast, ALD-DNA could not induce the generation of anti-dsDNA antibodies in nude mice. We further showed that in vivo depletion of CD3(+) T cells blocked the induction of anti-dsDNA antibodies in BALB/c mice. Notably, we demonstrated that CD4(+) but not CD8(+) T cells conferred ALD-DNA to induce anti-dsDNA antibodies. Finally, we demonstrated that adoptive transfer of CD4(+) T cells could rescue ALD-DNA induced anti-dsDNA antibodies in nude mice. Our results suggested that T helper cells were required for ALD-DNA to induce anti-dsDNA antibodies. These findings could further our understanding about the immunogenic properties of DNA and throw new light on SLE pathogenesis. PMID- 22300832 TI - Cytokine imbalance in systemic lupus erythematosus: a study on northern Indian subjects. AB - OBJECTIVE: The phenotype of systemic lupus erythematosus (SLE) in Asian Indians is more severe as compared with that in Caucasians. The reason is not clear. In this context, we studied serum levels of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4) and interlekin-10 (IL 10). Their interrelations and correlation with SLEDAI scores were evaluated. MATERIALS AND METHODS: Forty patients with active SLE and 40 controls were studied. The mean SLEDAI score and anti-ds DNA level of the patients were 21.45 +/- 8.61 and 176.68 +/- 81.31 (IU/ml), respectively. Cytokines were estimated by enzyme-linked immunosorbent assay. RESULTS: In controls, the levels of IFN-gamma were highest, followed by TNF-alpha, IL-10 & IL-4. In patients, however, the levels of TNF-alpha were highest, followed by IFN-gamma, IL-10 & IL-4. IL-10 and IL-4 correlated negatively, and IFN-gamma and TNF-alpha correlated positively with the SLEDAI scores. As compared with controls, in patients, the mean values of TNF-alpha, IL-10 and TNF-alpha/IL-10 ratio were higher by 6.9, 2.9 and 2.3 times, respectively (p < 0.001). Significant positive correlation was found between these two cytokines in patients (r = 0.327, p < 0.05) but not in controls. The levels and ratio of IL-4 and IFN-gamma were comparable between patients and controls. These two cytokines correlated negatively both in controls (r = -0.358, p < 0.05) and patients (r = -0.990, p < 0.001). The ratio of TNF alpha/IL-4 was 4.2 times higher, and those of IFN-gamma/IL-4 and IFN-gamma/IL-10 were 1.89 and 3.40 times lower in patients as compared with controls. A positive correlation between IL-10 and IL-4 (r = 0.345, p < 0.05) and a negative correlation between IL-10 and IFN-gamma (r = -0.382, p < 0.05) were observed only in patients. CONCLUSION: This study showed a distinct profile of cytokine imbalance in patients with SLE from the northern plains of India. The levels, ratios and correlations of cytokines in patients suggested significant deviation from normal. Correlations of cytokines with SLEDAI scores indicated that TNF alpha contributes significantly to the pathological manifestations of SLE in patients from the region. A detailed study is warranted. PMID- 22300833 TI - Multiple Spitz nevi: a clinicopathologic study of 9 patients. AB - BACKGROUND: Whether agminated, within a speckled lentiginous nevus/nevus spilus, or randomly scattered, multiple Spitz nevi (SN), defined as two or more SN, is a rare entity. OBJECTIVE: The aim of this study was to evaluate patients presenting with multiple SN. METHODS: We conducted a search of the database of the Yale Spitzoid Neoplasm Repository from May 1990 to June 2010 to identify patients with multiple SN. The clinicopathologic features of these patients are the subject of this study. RESULTS: Nine patients with a total of 38 SN were identified retrospectively during a 20-year period. Patients ranged in age from 2 to 34 years (mean 22 years). The total number of histologically confirmed SN in each patient ranged from 2 to 13 (mean 5; median 2). These SN were more commonly diagnosed clinically as atypical nevi rather than as SN. The histopathologic findings ranged from those of a classic SN to an atypical Spitzoid neoplasm that was difficult to distinguish from a Spitzoid melanoma. Of the SN examined histologically in this series, the majority (53%) showed no atypical histopathologic features and none had recurred after a re-excision. LIMITATIONS: The low number of patients with multiple SN is a limitation. CONCLUSION: The presence of multiple SN is a rare phenomenon. The majority display histopathologic characteristics of classic SN or a few atypical features. PMID- 22300834 TI - Anthocyanin kinetics are dependent on anthocyanin structure. AB - The kinetics of anthocyanin metabolism was investigated in a human feeding trial. Volunteers (n 12) consumed purple carrots containing five anthocyanin forms: cyanidin-3-(xylose-glucose-galactoside), cyanidin-3-(xylose-galactoside), cyanidin-3-(xylose-sinapoyl-glucose-galactoside), cyanidin-3-(xylose-feruloyl glucose-galactoside) and cyanidin-3-(xylose-coumuroyl-glucose-galactoside). The purple carrots were served as three different treatments in a crossover design with a 3-week washout between treatments. Purple carrot treatments were 250 g raw carrots, 250 g cooked carrots and 500 g cooked carrots. Serial blood and urine samples were collected for 8 and 24 h after the dose, respectively, and analysed for anthocyanins. Of the anthocyanin forms ingested, four were detected in plasma and urine: cyanidin-3-(xylose-glucose-galactoside), cyanidin-3-(xylose galactoside), cyanidin-3-(xylose-sinapoyl-glucose-galactoside) and cyanidin-3 (xylose-feruloyl-glucose-galactoside). The time courses of plasma and urine anthocyanin contents were evaluated with compartmental modelling. Results showed that absorption, gastrointestinal transit and plasma elimination are dependent on anthocyanin structure. Absorption efficiencies of acylated compounds (cyanidin-3 (xylose-sinapoyl-glucose-galactoside) and cyanidin-3-(xylose-feruloyl-glucose galactoside)) were less than those for non-acylated anthocyanins (cyanidin-3 (xylose-glucose-galactoside) and cyanidin-3-(xylose-galactoside)). The acylated anthocyanins exhibited a shorter half-life for gastrointestinal absorption than the non-acylated anthocyanins. Fractional elimination of non-acylated compounds was slower than that for acylated anthocyanins. These results provide the first information about the kinetics of individual anthocyanins in human beings. PMID- 22300835 TI - Memantine potentiates hippocampal theta oscillations at a therapeutic dose in anesthetized mice: a mechanistic link to its cognitive-enhancing properties. AB - Memantine is an uncompetitive, low-affinity NMDA receptor antagonist clinically used for the treatment of cognitive deficits in moderate to severe Alzheimer's disease. Both neurophysiological and behavioral studies in rodents have suggested a beneficial effect of memantine on synaptic plasticity and learning performances. In the present study, we investigated the effect of memantine on pedonculopontine-elicited theta oscillations in the hippocampus of urethane anesthetized mice, a model shown to be sensitive to several pharmacological agents exhibiting cognitive-enhancing properties. We found that a low dose of memantine potentiated elicited theta power while a high dose was disruptive. The low dose of memantine used was shown to yield an unbound brain concentration well within the range of therapeutic concentrations reported in rodent brain extracellular fluid and human cerebrospinal fluid. For further comparison, the effect of another uncompetitive NMDA receptor antagonist with higher affinity, i.e. MK-801, was also investigated. MK-801 was at a low dose devoid of effect on elicited theta power, while a high dose, within the range of doses reported to induce cognitive deficits in a variety of hippocampal-dependent learning paradigms in mice, was found disruptive on elicited theta waves. Taken together, our results suggest that clinically relevant doses of memantine promote neuronal network synchronization in the hippocampus, which may represent an underlying mechanism for the reported cognitive-enhancing properties in both preclinical and clinical studies. PMID- 22300836 TI - Heterocomplex formation of 5-HT2A-mGlu2 and its relevance for cellular signaling cascades. AB - Dopamine, serotonin and glutamate play a role in the pathophysiology of schizophrenia. In the brain a functional crosstalk between the serotonin receptor 5-HT(2A) and the metabotropic glutamate receptor mGlu(2) has been demonstrated. Such a crosstalk may be mediated indirectly through neuronal networks or directly by receptor oligomerization. A direct link of the 5-HT(2A)-mGlu(2) heterocomplex formation to receptor function, i.e. to intracellular signaling, has not been fully demonstrated yet. Here we confirm the formation of 5-HT(2A)-mGlu(2) heterocomplexes using quantitative Snap/Clip-tag based HTRF methods. Additionally, mGlu(2) formed complexes with 5-HT(2B) and mGlu(5) but not 5-HT(2C) indicating that complex formation is not specific to the 5-HT(2A)-mGlu(2) pair. We studied the functional consequences of the 5-HT(2A)-mGlu(2) heterocomplex addressing cellular signaling pathways. Co-expression of receptors in HEK-293 cells had no relevant effects on signaling mediated by the individual receptors when mGlu(2) agonists, antagonists and PAMs, or 5-HT(2A) hallucinogenic and non hallucinogenic agonists and antagonists were used. Hallucinogenic 5-HT(2A) agonists induced signaling through G(q/11), but not G(i) and thus did not lead to modulation of intracellular cAMP levels. In membranes of the medial prefrontal cortex [(3)H]-LY341495 binding competition of mGlu(2/3) agonist LY354740 was not influenced by 2,5-dimethoxy-4-iodoamphetamine (DOI). Taken together, the formation of GPCR heterocomplexes does not necessarily translate into second messenger effects. These results do not put into question the well-documented functional cross-talk of the two receptors in the brain, but do challenge the biological relevance of the 5-HT(2A)-mGlu(2) heterocomplex. PMID- 22300837 TI - Optimizing bone health in anorexia nervosa and hypothalamic amenorrhea: new trials and tribulations. PMID- 22300838 TI - Searching for people low in copper. PMID- 22300839 TI - Symposium on fresh whole blood for severe hemorrhagic shock: from in-hospital to far forward resuscitations. AB - This report is prepared for The Hemostasis and Oxygenation Research (THOR) Network and based on presentations of invited THOR investigators. In order to make it available to a larger group of interested readers it has been agreed to publish the report in TRASCI, as a "what is happening?" in view of its importance and novelty. On June 14th 2011 the first symposium on fresh whole blood (FWB) was held in Bergen, Norway. THOR network leadership, which includes Tor Hervig, PhD, MD, Geir Strandenes, MD, Erling Bekkestad Rein, MD, and Philip C. Spinella, MD, organized the event. It was sponsored by the Royal Norwegian Navy Medical Service, Norwegian Armed Forces Medical Services and Caridian BCT. The objective of this meeting was to bring together investigators from around the world who are interested in analyzing the efficacy and safety of FWB for patients with severe traumatic hemorrhagic shock and to determine the initial steps in developing a research program in this area. The THOR network is specifically interested in determining if FWB can improve morbidity and mortality in combat casualties with life threatening hemorrhagic shock. A three-year research proposal has been developed by the THOR network to determine (1) if FWB donation adversely affects donor performance of combat related skills, (2) the optimal storage solution, temperature, and acceptable storage duration for FWB, (3) the logistics of providing FWB in a combat environment safely to include optimal transport and administration methods. The symposium speakers were tasked with reviewing current data on; coagulopathy associated with massive traumatic bleeding, immunology of transfusion, outcomes associated with FWB use, logistic and medical issues of the use of FWB in far forward situations, training required for medics on FWB collection and administration, the risks of FWB and stored blood components and methods to mitigate these risks. The meeting concluded with a discussion of the THOR network's three-year research program. PMID- 22300840 TI - The prevalence of darunavir-associated mutations in HIV-1-infected children in the UK. AB - BACKGROUND: We examined the prevalence of ritonavir-boosted darunavir (DRV) resistance-associated mutations (RAMs) in HIV-infected children in the UK to determine the drug's potential clinical utility as a first-line or second-line protease inhibitor (PI). METHODS: The prevalence of DRV RAMs, identified from IAS 2010 and Stanford, and the Stanford susceptibility score, were estimated in PI naive and PI-experienced children in the Collaborative HIV Paediatric Study and the UK HIV Drug Resistance Database 1998-2008. Associations between type/duration of PI exposure and area under the viraemia curve on PI with the number of RAMs were investigated using multivariate Poisson regression. RESULTS: A total of 17/417 (4%) children with a resistance test when PI-naive had one IAS DRV RAM, and 1 had a Stanford mutation; none had multiple DRV RAMs. A total of 177 PI experienced children had a test after a median 2.7 years (IQR 1.1-5.2) on PIs; 19 (11%) had one IAS DRV RAM, 7 (4%) had two RAMs, 1 (0.6%) had three RAMs and 1 (0.6%) had four RAMs. DRV RAMs were independently associated with increased years on a PI, a larger area under the viraemia curve since starting PIs, and any exposure to PIs other than lopinavir (all P<=0.05). Only 6 (3%) PI-experienced children had intermediate-level DRV/ritonavir resistance; none had high-level resistance. CONCLUSIONS: DRV resistance was negligible in PI-naive children and those with lopinavir PI exposure alone. However resistance increased with increasing time, and with higher levels of viraemia, on PIs. Once-daily DRV/ritonavir would be valuable as a second PI or an alternative first PI, particularly if coformulated with a booster in an appropriate formulation for children. PMID- 22300841 TI - Accessibility of sexual health services in teenage sexual health service users: local area geospatial analysis. AB - BACKGROUND: Teenage pregnancy rates in the UK are the highest in Western Europe. Causes of teenage pregnancies are multifaceted with complex interplay of social, lifestyle and wider determinants influencing risk. Improving access to sexual health services through community services is an important factor in attempting to tackle this issue, but few studies have examined factors that influence this. METHODS: Geospatial analysis was conducted on community sexual health service users and teenage conceptions from local sexual health services were recorded. Univariate and multinomial regression was performed to test associations between service type and socio-economic status. RESULTS: No significant differences in accessibility of services between teenage girls who have conceived and those seeking sexual health services were found. Females aged 17 and under were more likely to use a young people's sexual health service than mainstream services (P < 0.001). However, a young person living in the most deprived quintiles was more likely to use a mainstream service if it was closer to their home address (adjusted odds ratios: 2.154, 95% confidence intervals: 1.533-3.027). CONCLUSIONS: Service type and socio-economic status impact upon the choices young people make when accessing community sexual health services. The study supports policy for locating young person services within the most deprived areas of a community. PMID- 22300842 TI - Phylogenetics of Chondrichthyes and the problem of rooting phylogenies with distant outgroups. AB - Erroneous estimates of ingroup relationships can be caused by attributes in the outgroup chosen to root the tree. Phylogenetic analyses of DNA sequences frequently yield incorrect estimates of ingroup relationships when the outgroup used to "root" the tree is highly divergent from the ingroup. This is especially the case when the outgroup has a different base composition than the ingroup. Unfortunately, in many instances, alternative less divergent outgroups are not available. In such cases, investigators must either target genes with attributes that minimize the problem (slowly evolving genes with stationary base compositions--which are often not ideal for estimating relationships among the more closely related ingroup taxa) or use inference models that are explicitly tailored to deal with an attenuated historical signal with a superimposed non stationary base composition. In this paper we explore the problem both empirically and through simulation. For the empirical component we looked at the phylogenetic relationships among elasmobranch fishes (sharks and rays), a group whose closest living outgroup, the holocephalan Ghost fishes, are separated from the elasmobranchs by more than 100 million years of evolution. We compiled a data set for analysis comprising 10 single-copy nuclear protein-coding genes (12,096 bp) for representatives of the major lineages within elasmobranchs and holocephalans. For the simulation, we used an evolutionary model on a fixed tree topology to generate DNA sequence data sets which varied both in their distance to the outgroup, and in their base compositional difference between ingroup and outgroup. Results from both the empirical data set and the simulation, support the idea that deviation from base compositional stationarity, in conjunction with distance from the root can act in concert to compromise accuracy of estimated relationships within the ingroup. We tested several approaches to mitigate such problems. We found, that excluding genes with overall faster rates and heterogeneous base compositions, while the least sophisticated of the methods evaluated, seemed to be the most effective. PMID- 22300843 TI - Prospective study of gait function before and 2 years after total knee arthroplasty. AB - PURPOSE: To perform a prospective evaluation of gait before and 2 years after total knee arthroplasty (TKA) and examine the influence of comorbidity and other joint problems on gait characteristics and their improvement after TKA. METHODS: One hundred and eleven patients scheduled for TKA took part (34 men, 65 +/- 10 y; 77 women, age 68 +/- 9 y). Gait velocity, cadence, and ground reaction force parameters were measured before and 2 years after surgery. Patients completed a questionnaire to rate their pain and other joint problems. Comorbidity was measured with the American Society of Anaesthesiologists (ASA) score. RESULTS: Two years after TKA there were significant improvements (each p<0.05) in gait velocity and cadence and most of the ground reaction parameters, though forces during loading/unloading remained lower for the operated leg than for the contralateral leg. Higher comorbidity and other painful joints of the lower extremities/spine had a consistent, negative influence (p<0.05) on the absolute values achieved for the gait parameters although their improvement compared with baseline was independent of these factors. CONCLUSIONS: Comorbidity and other joint problems negatively influenced gait performance. These confounders should be taken into account when setting realistic patient expectations and when interpreting the success of TKA in the individual patient. Improvement in gait is however still possible, within the bounds of concomitant comorbidity. PMID- 22300844 TI - Posterior cruciate substituting versus posterior cruciate retaining total knee arthroplasty prostheses: a meta-analysis. AB - PURPOSE: The arguments about whether posterior-substituting prostheses or cruciate-retaining prostheses are superior to the other after total knee arthroplasty never stop. This meta-analysis was conducted to evaluate the clinical effects of these two different designs. METHODS: The study was performed according to the guidelines described in the Cochrane handbook for systematic reviews of interventions. Methodological features were collected and extracted by two reviewers independently. RESULTS: Nine randomized controlled trials with 1261 knees were eligible for pooled analysis. The meta-analysis demonstrated there were no statistical differences in the Knee Society Score, Hospital for Special Surgery, Western Ontario and McMaster Universities index, tibial component alignment, femoral component alignment, tibial posterior slope, joint line, and incidence of complications with short-to medium-term follow-up (p>0.01). Statistically difference in postoperative range of motion (WMD: 4.34 degrees , 95% CI: 3.18 degrees to 5.50 degrees ) in favor of PS prostheses was found between groups (p<0.01). CONCLUSION: The findings indicate there were no significant statistical differences in knee scores, radiological outcomes, and complications between the two types of implants. Statistically significant difference in postoperative ROM was found between the two groups, but no clinical difference. PMID- 22300845 TI - Relationships between lumbar bone mineral density and biochemical parameters in phenylketonuria patients. AB - BACKGROUND: The etiology of reduced bone mineral density (BMD) in phenylketonuria (PKU) is unknown. Reduced BMD may be inherent to PKU and/or secondary to its dietary treatment. MATERIALS AND METHODS: Lumbar BMD was measured by dual-energy X-ray absorptiometry in 53 early and continuously treated PKU patients (median age 16, range 2-35 years). First, Z-scores of BMD were correlated to age group, clinical severity of PKU, mean phenylalanine (Phe) concentration and Phe variation in the year prior to DXA scanning, as well as to blood vitamin, mineral, and alkaline phosphatase concentrations. Second, parameters were compared between subjects with reduced BMD (Z-score<-2 SD) and subjects with normal BMD. RESULTS: BMD was significantly reduced in our cohort (p=0.000). Z scores of BMD were neither significantly correlated to age group, nor clinical severity of PKU. Both mean Phe concentration and Phe variation in the year prior to DXA scanning did not significantly correlate with Z-scores of BMD. Higher blood calcium concentrations were significantly associated with lower BMD (r(2)= 0.485, p=0.004). Other biochemical parameters, including vitamin B12 availability markers, did not show significant correlations with Z-score of BMD. Subjects with reduced BMD had significantly higher blood phosphorus concentrations than subjects with normal BMD (p=0.009). No other significant differences were found between both BMD groups. CONCLUSION: Reduced BMD in PKU is present from early age onward and does not progress with age. Therefore, BMD deserves attention from early age onward in PKU patients. Our findings are consistent with increased bone turnover in PKU. It remains unclear whether reduced BMD is inherent to PKU and/or secondary to its dietary treatment. PMID- 22300846 TI - SIMD statement on investigational new drugs for rare disease therapies. PMID- 22300847 TI - Quantification of phenylalanine hydroxylase activity by isotope-dilution liquid chromatography-electrospray ionization tandem mass spectrometry. AB - BACKGROUND: Residual phenylalanine hydroxylase (PAH) activity is the key determinant for the phenotype severity in phenylketonuria (PKU) patients and correlates with the patient's genotype. Activity of in vitro expressed mutant PAH may predict the patient's phenotype and response to tetrahydrobiopterin (BH(4)), the cofactor of PAH. METHODS: A robust LC-ESI-MSMS PAH assay for the quantification of phenylalanine and tyrosine was developed. We measured PAH activity a) of the PAH mutations p.Y417C, p.I65T, p.R261Q, p.E280A, p.R158Q, p.R408W, and p.E390G expressed in eukaryotic COS-1 cells; b) in different cell lines (e.g. Huh-7, Hep3B); and c) in liver, brain, and kidney tissue from wild type and PKU mice. RESULTS: The PAH assay was linear for phenylalanine and tyrosine (r(2)>=0.99), with a detection limit of 105 nmol/L for Phe and 398 nmol/L for Tyr. Intra-assay and inter-assay coefficients of variation were <5.3% and <6.2%, respectively, for the p.R158Q variant in lower tyrosine range. Recovery of tyrosine was 100%. Compared to the wild-type enzyme, the highest PAH activity at standard conditions (1 mmol/L L-Phe; 200 MUmol/L BH(4)) was found for the mutant p.Y417C (76%), followed by p.E390G (54%), p.R261Q (43%), p.I65T (33%), p.E280A (15%), p.R158Q (5%), and p.R408W (2%). A relative high PAH activity was found in kidney (33% of the liver activity), but none in brain. CONCLUSIONS: This novel method is highly sensitive, specific, reproducible, and efficient, allowing the quantification of PAH activity in different cells or tissue extracts using minimum amounts of samples under standardized conditions. PMID- 22300848 TI - Field-effect tunneling transistor based on vertical graphene heterostructures. AB - An obstacle to the use of graphene as an alternative to silicon electronics has been the absence of an energy gap between its conduction and valence bands, which makes it difficult to achieve low power dissipation in the OFF state. We report a bipolar field-effect transistor that exploits the low density of states in graphene and its one-atomic-layer thickness. Our prototype devices are graphene heterostructures with atomically thin boron nitride or molybdenum disulfide acting as a vertical transport barrier. They exhibit room-temperature switching ratios of ~50 and ~10,000, respectively. Such devices have potential for high frequency operation and large-scale integration. PMID- 22300849 TI - Founder effects persist despite adaptive differentiation: a field experiment with lizards. AB - The extent to which random processes such as founder events contribute to evolutionary divergence is a long-standing controversy in evolutionary biology. To determine the respective contributions of founder effects and natural selection, we conducted an experiment in which brown anole (Anolis sagrei) lizard populations were established on seven small islands in the Bahamas, from male female pairs randomly drawn from the same large-island source. These founding events generated significant among-island genetic and morphological differences that persisted throughout the course of the experiment despite all populations adapting in the predicted direction-shorter hindlimbs-in response to the narrower vegetation on the small islands. Thus, using a replicated experiment in nature, we showed that both founder effects and natural selection jointly determine trait values in these populations. PMID- 22300850 TI - ER cargo properties specify a requirement for COPII coat rigidity mediated by Sec13p. AB - Eukaryotic secretory proteins exit the endoplasmic reticulum (ER) via transport vesicles generated by the essential coat protein complex II (COPII) proteins. The outer coat complex, Sec13-Sec31, forms a scaffold that is thought to enforce curvature. By exploiting yeast bypass-of-sec-thirteen (bst) mutants, where Sec13p is dispensable, we probed the relationship between a compromised COPII coat and the cellular context in which it could still function. Genetic and biochemical analyses suggested that Sec13p was required to generate vesicles from membranes that contained asymmetrically distributed cargoes that were likely to confer opposing curvature. Thus, Sec13p may rigidify the COPII cage and increase its membrane-bending capacity; this function could be bypassed when a bst mutation renders the membrane more deformable. PMID- 22300851 TI - Extremely long-lived nuclear pore proteins in the rat brain. AB - To combat the functional decline of the proteome, cells use the process of protein turnover to replace potentially impaired polypeptides with new functional copies. We found that extremely long-lived proteins (ELLPs) did not turn over in postmitotic cells of the rat central nervous system. These ELLPs were associated with chromatin and the nuclear pore complex, the central transport channels that mediate all molecular trafficking in and out of the nucleus. The longevity of these proteins would be expected to expose them to potentially harmful metabolites, putting them at risk of accumulating damage over extended periods of time. Thus, it is possible that failure to maintain proper levels and functional integrity of ELLPs in nonproliferative cells might contribute to age-related deterioration in cell and tissue function. PMID- 22300852 TI - Pollinator-mediated selection on flower color allele drives reinforcement. AB - Reinforcement is the process by which reduced hybrid fitness generates selection favoring the evolution of stronger prezygotic reproductive barriers between emerging species. Using common-garden field experiments, we quantified the strength of reinforcing selection in nature by demonstrating strong selection favoring an allele conferring increased pigment intensity in the plant Phlox drummondii in areas of sympatry with the closely related species Phlox cuspidata. Incomplete hybrid sterility between the two species generates selection for traits that decrease interspecies hybridization. In contrast, selection on this locus is undetectable in the absence of P. cuspidata. We demonstrate that reinforcing selection is generated by nonrandom pollinator movement, in which pollinators move less frequently between intensely pigmented P. drummondii and P. cuspidata than between lightly pigmented P. drummondii and P. cuspidata. PMID- 22300853 TI - Ovarian cancer: breaking the silence. PMID- 22300854 TI - Medical paternalism: who knows best? PMID- 22300855 TI - A tale of two tumours and a plea for progress. PMID- 22300857 TI - Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine. PMID- 22300858 TI - A STEPP too far for FLEX? PMID- 22300860 TI - Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. AB - Here we provide the updated version of the guidelines of the European Association for Palliative Care (EAPC) on the use of opioids for the treatment of cancer pain. The update was undertaken by the European Palliative Care Research Collaborative. Previous EAPC guidelines were reviewed and compared with other currently available guidelines, and consensus recommendations were created by formal international expert panel. The content of the guidelines was defined according to several topics, each of which was assigned to collaborators who developed systematic literature reviews with a common methodology. The recommendations were developed by a writing committee that combined the evidence derived from the systematic reviews with the panellists' evaluations in a co authored process, and were endorsed by the EAPC Board of Directors. The guidelines are presented as a list of 16 evidence-based recommendations developed according to the Grading of Recommendations Assessment, Development and Evaluation system. PMID- 22300861 TI - Chordoma: current concepts, management, and future directions. AB - Chordoma is a rare bone cancer that is aggressive, locally invasive, and has a poor prognosis. Chordomas are thought to arise from transformed remnants of notochord and have a predilection for the axial skeleton, with the most common sites being the sacrum, skull base, and spine. The gold standard treatment for chordomas of the mobile spine and sacrum is en-bloc excision with wide margins and postoperative external-beam radiation therapy. Treatment of clival chordomas is unique from other locations with an enhanced emphasis on preservation of neurological function, typified by a general paradigm of maximally safe cytoreductive surgery and advanced radiation delivery techniques. In this Review, we highlight current standards in diagnosis, clinical management, and molecular characterisation of chordomas, and discuss current research. PMID- 22300862 TI - Consensus-based standards for best supportive care in clinical trials in advanced cancer. AB - Best supportive care is poorly defined in clinical trials, and a standard framework for delivery of such care is needed, using best available evidence and allowing replication of studies. We convened a panel of 36 experts to develop consensus statements via the Delphi method. The first round included open-ended questions; subsequent rounds sought to develop consensus-based standards. Consensus was assessed by use of a 5-point Likert agreement scale; more than 70% of panellists had to give a score of 5 to meet a-priori levels of consensus. The panel identified four key domains of best supportive care in clinical trials: multidisciplinary care; supportive care documentation; symptom assessment; and symptom management. Consensus was reached on 11 statements within these four domains. For example, 24 (96%) panellists recommended that the intervals between symptom assessments should be identical for control and experimental groups. Availability of resources was cited as a challenge to implementation of best supportive care standards. PMID- 22300863 TI - The developing cancer stem-cell model: clinical challenges and opportunities. AB - During the past decade, a stem-cell-like subset of cancer cells has been identified in many malignancies. These cells, referred to as cancer stem cells (CSCs), are of particular interest because they are believed to be the clonogenic core of the tumour and therefore represent the cell population that drives growth and progression. Many efforts have been made to design therapies that specifically target the CSC population, since this was predicted to be the crucial population to eliminate. However, recent insights have complicated the initial elegant model, by showing a dominant role for the tumour microenvironment in determining CSC characteristics within a malignancy. This is particularly important since dedifferentiation of non-tumorigenic tumour cells towards CSCs can occur, and therefore the CSC population in a neoplasm is expected to vary over time. Moreover, evidence suggests that not all tumours are driven by rare CSCs, but might instead contain a large population of tumorigenic cells. Even though these results suggest that specific targeting of the CSC population might not be a useful therapeutic strategy, research into the hierarchical cellular organisation of malignancies has provided many important new insights in the biology of tumours. In this Personal View, we highlight how the CSC concept is developing and influences our thinking on future treatment for solid tumours, and recommend ways to design clinical trials to assess drugs that target malignant disease in a rational fashion. PMID- 22300864 TI - Antipsychotic medication and prefrontal cortex activation: a review of neuroimaging findings. AB - Decreased prefrontal activation (hypofrontality) in schizophrenia is thought to underlie negative symptoms and cognitive impairments, and may contribute to poor social outcome. Hypofrontality does not always improve during treatment with antipsychotics. We hypothesized that antipsychotics, which share antagonism at dopamine receptors, with a relatively low dopamine receptor affinity and high serotonin receptor affinity may have a sparing effect on prefrontal function compared to strong dopamine receptor antagonists. We systematically investigated the relation between serotonin and dopamine antagonism of antipsychotics and prefrontal functioning by reviewing neuroimaging studies. The weight of the evidence was consistent with our hypothesis that antipsychotics with low dopaminergic receptor affinity and moderate to high serotonergic affinity were associated with higher activation of the prefrontal cortex. However, clozapine, a weak dopamine and strong serotonin antagonist, was associated with decrease in prefrontal activation. Future studies should further elucidate the link between prefrontal activation and negative symptoms using prospective designs and advanced neuroimaging techniques, which may ultimately benefit the development of treatments for disabling negative symptoms. PMID- 22300865 TI - Fluorescence in situ hybridization (FISH) detection of nitrite reductase transcripts (nirS mRNA) in Pseudomonas stutzeri biofilms relative to a microscale oxygen gradient. AB - Microsensor measurements of oxygen were combined with mRNA-targeted fluorescence in situ hybridization (FISH) to relate the expression of nitrite reductase (nirS) to oxygen concentrations in artificial biofilms of the denitrifier Pseudomonas stutzeri. A distinct zone of nirS transcript-containing cells was detected at the oxic-anoxic transition zone, below an oxygen threshold concentration of 0.7 2.5MUM, depending on incubation conditions. Although not a routine technique yet, the possibility of coupling microsensor and mRNA-targeted FISH analyses described here opens for studies addressing microenvironment, identity, and actual activity of microbes in stratified environments at single cell resolution. PMID- 22300866 TI - What causes hepatitis A in travellers to endemic countries? Travel is necessary but not sufficient--a risk factor, not a cause. PMID- 22300867 TI - Endoscopic forehead lift in patients with male pattern baldness. AB - PURPOSE: The presence of male pattern baldness poses a significant challenge when attempting to optimize treatment of the upper third of the face. The purpose of this study is to demonstrate and discuss results of the endoscopic forehead lift in patients with male pattern baldness. MATERIALS AND METHODS: This was a retrospective case series done in an academic medical center. Eleven patients with male pattern baldness (Norwood class IV-VII) underwent endoscopic forehead lift for forehead creases and brow ptosis. RESULTS: All patients achieved smoothing of the forehead and elevation of the brow with no scalp anesthesia at 1 month postoperatively. All patients were pleased with the healing of their incisions in midline, paramedian, and temporal regions. Alloplastic fixation devices used were visible postoperatively in 2 patients initially. CONCLUSIONS: The endoscopic forehead lift is a suitable approach for treating the upper third of the face in the presence of male pattern baldness. The use of alloplastic fixation devices may be used in this patient population, but other fixation methods should be considered. PMID- 22300868 TI - Feasibility of partnering with emergency medical services to identify people at risk for uncontrolled high blood pressure. AB - INTRODUCTION: Uncontrolled high blood pressure (HBP) is a significant health problem and often goes undetected. In the prehospital care-delivery system of 9-1 1 emergency medical services (EMS) calls, emergency medical technicians (EMTs) routinely collect medical information, including blood pressure values, that may indicate the presence of chronic disease. This information is usually archived without any further follow-up. We conducted several planning activities during the fall of 2006 to determine if a partnership between researchers at the Health Marketing Research Center at the University of Washington, Public Health Seattle King County EMS division, and several large fire departments could be developed to help identify community residents with uncontrolled HBP and determine the most effective way to communicate HBP information to them. METHODS: We partnered with 4 King County, Washington, fire departments that provide 9-1-1 EMS to develop an intervention for people with uncontrolled HBP who were attended by EMTs in response to a 9-1-1 call for assistance. On the basis of discussions with EMS personnel at all levels, we developed a system by which we could identify at-risk community residents by using medical incident report forms that EMS personnel completed; we consulted with EMS personnel to determine the most effective means of reaching these people. In addition we developed a survey to assess community residents' beliefs about blood pressure control, the role of EMTs as health care providers, and the convenience of fire stations as places to have blood pressure checked. Using contact information that EMS personnel obtained, we surveyed 282 community residents from a total of 794 people whom EMTs had identified as at risk for uncontrolled HBP to help us understand our target audience. RESULTS: In consultation with EMS personnel, we determined that direct mail was the most effective way to reach people with uncontrolled HBP identified from EMS records to advise them of their risk. On the basis of the number with a known response to each question, 67% (n = 180/269) of the respondents reported that a doctor or other health professional had told them they had HBP, 95% (246/259) believed that regular screening for HBP was important, 65% (166/254) said that EMTs were highly credible health care providers, and 82% (136/165) said that they would feel comfortable receiving blood pressure screening at a local fire station. CONCLUSION: Partnering with local EMS may be an effective way to identify and reach community residents with uncontrolled HBP with information on their medical condition and to encourage them to have follow-up screening. PMID- 22300869 TI - The simple health system rules that create value. AB - In 1991, Plsek sought to improve the quality of health care by challenging the readers of Crossing the Quality Chasm to find the few simple rules that might guide the local development of the 21st century health system. We have analyzed our health system's activities in the context of systems science as it seeks to create value (improve population health and patient experience, and reduce costs) for its stakeholders. We have concluded that 5 rules are simultaneously necessary and sufficient for success: 1) The stakeholders agree on a set of mutual, measurable goals for the health system; 2) the extent to which the goals are being achieved is reported to the public; 3) resources are available to achieve the goals; 4) stakeholder incentives, imperatives, and sanctions are aligned with the agreed-on health system goals; and 5) leaders among all stakeholders endorse and promote the agreed-on health system goals. PMID- 22300870 TI - The evolution of the steps program, 2003-2010: transforming the federal public health practice of chronic disease prevention. AB - The Steps program, formerly known as Steps to a HealthierUS, was the first Centers for Disease Control and Prevention (CDC) program to support a community based, integrated approach to chronic disease prevention. Steps interventions addressed both diseases and risk factors, focusing on the 3 leading causes of preventable deaths in the United States--tobacco use, poor nutrition, and physical inactivity--and the associated chronic conditions of asthma, diabetes, and obesity. When Steps shifted from interventions focused on individual health risk behaviors to the implementation of policy, systems, and environmental changes, the program became an integral part of changing the way CDC addressed chronic disease prevention. In this article, we describe the shift in intervention strategies that occurred among Steps communities, the model that was developed as Steps evolved, common interventions implemented before and after the shift in approach, challenges experienced by Steps communities, and CDC programs that were modeled after Steps. PMID- 22300871 TI - Benefits of a primary care clinic co-located and integrated in a mental health setting for veterans with serious mental illness. AB - INTRODUCTION: Efficacy trials have shown that primary care co-located in the mental health setting improves the receipt of high-quality medical care among people with serious mental illness. We tested whether implementation of such a program affected health service use and cardiovascular risk factor control among veterans with serious mental illness who had previously demonstrated limited primary care engagement. METHODS: We performed a cohort study of veterans enrolled in a co-located, integrated primary care clinic in the mental health outpatient unit through targeted chart review. Two successive 6-month periods in the year before and in the year following enrollment in the co-located primary care clinic were examined for primary care and emergency department use and for goal attainment of blood pressure, fasting blood lipids, body mass index (BMI), and, among patients with diabetes, hemoglobin A1c (HbA1c). We used repeated measures logistic regression to analyze goal attainment and repeated measures Poisson regression to analyze service use. RESULTS: Compared with the period before enrollment, the 97 veterans enrolled in the clinic had significantly more primary care visits during 6 months and significantly improved goal attainment for blood pressure, low-density lipoprotein cholesterol, triglycerides, and BMI. Changes with regard to goal attainment for high-density lipoprotein cholesterol and HbA1c were not significant. CONCLUSION: Enrollment in a co-located, integrated clinic was associated with increased primary care use and improved attainment of some cardiovascular risk goals among veterans with serious mental illness. Such a clinic can be implemented effectively in the mental health setting. PMID- 22300872 TI - Validation of the rapid assessment procedure for loiasis (RAPLOA) in the Democratic Republic of Congo. AB - BACKGROUND: A simple method called RAPLOA, to rapidly assess what proportion of people in a community are infected with L. loa and hence which communities are at high risk of severe adverse reactions following ivermectin treatment, was developed in Cameroon and Nigeria. The method needed further validation in other geographical and cultural contexts before its application in all endemic countries. The present study was designed to validate RAPLOA in two regions in the North East and South West of the Democratic Republic of Congo. METHODS: In each study region, villages were selected from different bio-ecological zones in order to cover a wide range of loiasis endemicity. In each selected community, 80 people above the age of 15 years were interviewed for a history of eye worm (migration of adult L. loa under the conjunctiva of the eye) and parasitologically examined for the presence and intensity of L. loa infection. In total, 8100 individuals from 99 villages were enrolled into the study. RESULTS: The results confirmed the findings of the original RAPLOA study: i) the eye worm phenomenon was well-known in all endemic areas, ii) there was a clear relationship between the prevalence of eye worm history and the prevalence and intensity of L. loa microfilaraemia, and iii) using a threshold of 40%, the prevalence of eye worm history was a sensitive and specific indicator of high risk communities. CONCLUSION: Following this successful validation, RAPLOA was recommended for the assessment of loiasis endemicity in areas targeted for ivermectin treatment by lymphatic filariasis and onchocerciasis control programmes. PMID- 22300874 TI - Inherited prion disease with 4-octapeptide repeat insertion linked to valine at codon 129. PMID- 22300875 TI - Pictures as a neurological tool: lessons from enhanced and emergent artistry in brain disease. AB - Pictures created spontaneously by patients with brain disease often display impaired or diminished artistry, reflecting the patient's cerebral damage. This article explores the opposite: those pictures created in the face of brain disease that show enhanced or enduring artistry, and those that emerge for the first time in artistically naive patients. After comments on background issues relating to the patient and the viewer, the paintings and drawings are considered in relation to the heterogeneous conditions in which this artistic creativity is seen. These conditions include various dementias-most notably frontotemporal lobar dementia, stroke, Parkinson's disease, autism and related disorders and psychiatric disease, epilepsy, migraine and trauma. In the discussion, it is argued that evidence of underlying brain dysfunction revealed by these pictures often rests on the abnormal context in which the pictures are created, or on changes in artistry demonstrated by a sequence of pictures. In the former, the compulsive element and sensory and emotional accompaniments are often important features; in the latter, evolving changes are evident, and have included depiction of increasing menace in portrayal of faces. The occurrence of synaesthesia, and its relation to creativity, are briefly discussed in respect of two unusual patients, followed by considering the role of the anterior and frontal lobes, mesolimbic connections and the right hemisphere. In at least some patients, impaired inhibition leading to paradoxical functional facilitation, with compensatory changes particularly in the right posterior hemisphere, is likely to be pivotal in enabling unusual artistry to emerge; preservation of language, however, is not a prerequisite. Many patients studied have been artists, and it appears possible that some of those with an artistic predisposition may be more likely to experience pathologically obsessive creativity. The discussion concludes that occasionally pictures created by these rare individuals unexpectedly prove to be an invaluable but little studied tool for investigating the dysfunctioning brain. PMID- 22300873 TI - Distinct clinical and pathological characteristics of frontotemporal dementia associated with C9ORF72 mutations. AB - The identification of a hexanucleotide repeat expansion in the C9ORF72 gene as the cause of chromosome 9-linked frontotemporal dementia and motor neuron disease offers the opportunity for greater understanding of the relationship between these disorders and other clinical forms of frontotemporal lobar degeneration. In this study, we screened a cohort of 398 patients with frontotemporal dementia, progressive non-fluent aphasia, semantic dementia or mixture of these syndromes for mutations in the C9ORF72 gene. Motor neuron disease was present in 55 patients (14%). We identified 32 patients with C9ORF72 mutations, representing 8% of the cohort. The patients' clinical phenotype at presentation varied: nine patients had frontotemporal dementia with motor neuron disease, 19 had frontotemporal dementia alone, one had mixed semantic dementia with frontal features and three had progressive non-fluent aphasia. There was, as expected, a significant association between C9ORF72 mutations and presence of motor neuron disease. Nevertheless, 46 patients, including 22 familial, had motor neuron disease but no mutation in C9ORF72. Thirty-eight per cent of the patients with C9ORF72 mutations presented with psychosis, with a further 28% exhibiting paranoid, deluded or irrational thinking, whereas <4% of non-mutation bearers presented similarly. The presence of psychosis dramatically increased the odds that patients carried the mutation. Mutation bearers showed a low incidence of motor stereotypies, and relatively high incidence of complex repetitive behaviours, largely linked to patients' delusions. They also showed a lower incidence of acquired sweet food preference than patients without C9ORF72 mutations. Post-mortem pathology in five patients revealed transactive response DNA-binding protein 43 pathology, type A in one patient and type B in three. However, one patient had corticobasal degeneration pathology. The findings indicate that C9ORF72 mutations cause some but not all cases of frontotemporal dementia with motor neuron disease. Other mutations remain to be discovered. C9ORF72 mutations are associated with variable clinical presentations and pathology. Nevertheless, the findings highlight a powerful association between C9ORF72 mutations and psychosis and suggest that the behavioural characteristics of patients with C9ORF72 mutations are qualitatively distinct. Mutations in the C9ORF72 gene may be a major cause not only of frontotemporal dementia with motor neuron disease but also of late onset psychosis. PMID- 22300876 TI - The clinical and pathological phenotype of C9ORF72 hexanucleotide repeat expansions. AB - There is increasing evidence that frontotemporal dementia and amyotrophic lateral sclerosis are part of a disease continuum. Recently, a hexanucleotide repeat expansion in C9orf72 was identified as a major cause of both sporadic and familial frontotemporal dementia and amyotrophic lateral sclerosis. The aim of this study was to investigate clinical and neuropathological characteristics of hexanucleotide repeat expansions in C9orf72 in a large cohort of Dutch patients with frontotemporal dementia. Repeat expansions were successfully determined in a cohort of 353 patients with sporadic or familial frontotemporal dementia with or without amyotrophic lateral sclerosis, and 522 neurologically normal controls. Immunohistochemistry was performed in a series of 10 brains from patients carrying expanded repeats using a panel of antibodies. In addition, the presence of RNA containing GGGGCC repeats in paraffin-embedded sections of post-mortem brain tissue was investigated using fluorescence in situ hybridization with a locked nucleic acid probe targeting the GGGGCC repeat. Hexanucleotide repeat expansions in C9orf72 were found in 37 patients with familial (28.7%) and five with sporadic frontotemporal dementia (2.2%). The mean age at onset was 56.9 +/- 8.3 years (range 39-76), and disease duration 7.6 +/- 4.6 years (range 1-22). The clinical phenotype of these patients varied between the behavioural variant of frontotemporal dementia (n = 34) and primary progressive aphasia (n = 8), with concomitant amyotrophic lateral sclerosis in seven patients. Predominant temporal atrophy on neuroimaging was present in 13 of 32 patients. Pathological examination of the 10 brains from patients carrying expanded repeats revealed frontotemporal lobar degeneration with neuronal transactive response DNA binding protein-positive inclusions of variable type, size and morphology in all brains. Fluorescence in situ hybridization analysis of brain material from patients with the repeat expansion, a microtubule-associated protein tau or a progranulin mutation, and controls did not show RNA-positive inclusions specific for brains with the GGGGCC repeat expansion. The hexanucleotide repeat expansion in C9orf72 is an important cause of frontotemporal dementia with and without amyotrophic lateral sclerosis, and is sometimes associated with primary progressive aphasia. Neuropathological hallmarks include neuronal and glial inclusions, and dystrophic neurites containing transactive response DNA binding protein. Future studies are needed to explain the wide variation in clinical presentation. PMID- 22300877 TI - The time course of retrograde trans-synaptic degeneration following occipital lobe damage in humans. AB - Following damage to the human post-geniculate visual pathway retrograde trans synaptic degeneration of the optic nerve fibres occurs. It has been known for some time from investigations carried out in primates that a decline in the number of retinal ganglion cells follows occipital lobectomy. However, this is not detectable in all species studied and whether this occurs in humans was controversial until recent studies that have shown that following lesions of the occipital lobe, the retinal nerve fibre layer thickness measured by optical coherence tomography is reduced and corresponding shrinkage of the optic tract can be demonstrated by magnetic resonance imaging. The time course of the degeneration in humans is, however, unknown. In the present study, we have used optical coherence tomography to demonstrate for the first time progressive thinning of the retinal nerve fibre layer following occipital lobe/optic radiation damage due to stroke. First, in a group of 38 patients the measurement was taken on a single occasion at a known time interval since the stroke, ranging from 6 days to 67 years. Here, a negative straight line relationship (linear regression r = 0.54, P < 0.001) was found between nerve fibre layer thickness and elapsed time since injury in log years, giving a rate of decline of 9.08 um per log year after adjusting for age. This indicates a decelerating rate of loss that differs from the rate of decline found with chronological age in this same group, which shows a steady rate of thinning by 0.4 um per year (P = 0.006) after adjusting for duration of the disease. In a second study serial measurements were taken following the acute event in a group of seven patients with homonymous hemianopia; here a negative straight line relationship was found between time and nerve fibre layer thickness in micrometres over a period of data collection beginning at a mean of 36.9 days post-stroke (range 5-112) and ending at a mean of 426.6 days post-stroke (range 170-917). Evidence from clinical observation (funduscopy) suggested that retrograde trans-synaptic degeneration occurred in humans only where the damage to the post-geniculate pathway occurred prenatally. The results reported herein add weight to the previous demonstration that this type of degeneration does indeed occur in the human visual system by showing that it can be monitored over time and hence may provide a model for trans-synaptic degeneration in the human central nervous system. PMID- 22300878 TI - Opa1 is essential for retinal ganglion cell synaptic architecture and connectivity. AB - Retinal ganglion cell dendritic pruning has been reported in association with a 50% reduction in Opa1 transcript and protein in retinal and neural tissue, which manifests as visual dysfunction in the heterozygous mutant mouse, B6;C3 Opa1(Q285STOP). Here we report a marked reduction in retinal ganglion cell synaptic connectivity in the absence of soma loss and explore the mechanism and relationship between mitochondrial integrity and synaptic connectivity. We observed decreased levels of postsynaptic density protein 95 in Opa1(+/-) mutant mice consistent with synaptic loss in the inner plexiform layer. Glutamatergic but not gamma-aminobutyric acid-ergic synaptic sites were reduced in Opa1(+/-) mice. We observed increased synaptic vesicle number in bipolar cell terminal arbours assessed by immunohistochemistry, electron microscopy and western blot analysis. These changes occur without significant loss of mitochondrial membrane potential in retina and optic nerve. Analysis of biolistically transfected retinal ganglion cells shows the retraction of mitochondria towards the soma, and mitochondrial fragmentation, preceding dendritic loss. These processes cast light on the intimate relationship between normal mitochondrial fusion and fission balances, as influenced by the OPA1 protein, in neural cell connectivity in the mammalian retina. PMID- 22300879 TI - The clinical, quality of life, and economic consequences of chronic anemia and transfusion support in patients with myelodysplastic syndromes. AB - Most patients with myelodysplastic syndromes (MDS) require transfusions due to chronic anemia. Apart from the acute risks associated with transfusions, chronic anemia and red blood cell (RBC) transfusion dependence impact negatively on survival and quality of life (QoL), and are associated with iron overload, potentially leading to organ damage. QoL studies demonstrate that regular transfusions do not correct the impact of chronic anemia. Furthermore, chronic transfusion support requires substantial resources. Therefore, major goals are to prevent or effectively treat anemia. Indeed, innovative drugs have been shown to be effective in achieving transfusion independence by altering the natural course of MDS. PMID- 22300880 TI - The multiple-lemma representation of Italian compound nouns: a single case study of deep dyslexia. AB - It is not clear how compound words are represented within the influential framework of the lemma-lexeme theory. Theoretically, compounds could be structured through a multiple lemma architecture, in which the lemma nodes of both the compound and its constituents are involved in lexical processing. If this were the case, syntactic properties of both the compound and its constituents should play a role when performing tasks involving compound processing, e.g., compound-word reading. This issue is investigated in the present study through an assessment of the performance of a deep dyslexic patient (GR) in three compound-reading experiments. In the first experiment, verb-noun (VN) compound nouns (e.g., lavapiatti, "dishwasher", lit. wash-dishes) were employed as stimuli, while in the second, VN compound stimuli were embedded in sentences, and were compared to paired verb phrases (e.g., lui lava piatti, "he washes dishes"). Position-specific effects were ruled out by means of a third experiment, which investigated the retrieval of noun-noun compounds (e.g., pescespada, "swordfish", lit. fishsword). In experiment 1, GR made errors on the verb constituent more frequently than on the noun, an effect that did not emerge in Experiment 2: when embedded in sentences, VN compounds were read significantly better than verb-phrases and no grammatical-class effect emerged. In Experiment 3, the first and the second constituent were read with the same level of accuracy. The disproportionate impairment, which emerged in reading the verb component of nominal VN compounds, indicates that the grammatical properties of constituents are being retrieved, and thus confirms access to the constituent lemma-nodes. However, the results suggested a whole-word representation when compounds are embedded in sentences; since the sentence context affects the access to compounds through syntactic constraints, whole-word representation is arguably at the lemma level as well (multiple-lemma representation). Experiment 3 indicates that these effects cannot be accounted for by a position-specific impairment. PMID- 22300881 TI - Valuing health: a brief report on subjective well-being versus preferences. PMID- 22300882 TI - [Effectiveness and safety of goal directed nurse-led blood glucose control in an intensive care unit: a prospective observational study]. AB - OBJECTIVE: to evaluate the effectiveness and safety of a nurse-led blood glucose control protocol in a medical ICU. METHOD: a descriptive, prospective study was carried out for a period of 13 months. All blood glucose values from patients on insulin therapy for intensive glycemic control were recorded daily. RESULTS: A total of 12,677 blood glucose determinations were performed on the 69 patients under glycemic control; 57.9% of the determinations had predetermined study target values for blood glucose (100-140 mg/dl) and 68.8% of the determinations had physiological blood glucose values (80-140 mg/dl); no values under 40 mg/dl were obtained, and only 0.2% were between 40-60 mg/dl. CONCLUSIONS: For an adequate blood glucose control using intensive insulin therapy, individual management of insulin infusion regimen is essential, adjusted to the characteristics of each patient. A nurse-led intervention has allowed better results to be obtained in comparison with other studies in which different protocols for insulin infusion are used. PMID- 22300883 TI - [Limiting and facilitating factors of changes in the care of families of the critically ill patient]. AB - INTRODUCTION: Participatory action research (PAR) was conducted in an intensive care unit (UCI), with the general purpose of fostering change in clinical practice so as to improve the care offered to families of critically ill patients. As a result of this process, four change-related initiatives were introduced. One specific additional objective was to explore how the unit's background context limited or facilitated change. This paper presents findings based on this objective. MATERIALS AND METHODS: Qualitative methodology. DESIGN: Participatory-action research (PAR). DATA GATHERING TECHNIQUES: 11 discussion groups incorporating professionals, 5 in-depth interviews with professionals, field diaries kept by the participants, and field diary kept by the lead researcher. Eleven professionals took part in the discussion groups (each one conveyed information made known to them by 3-5 colleagues), 5 professionals were involved in the interviews, and 11 professionals filled in a field diary. A content analysis was performed. RESULTS: Factors limiting change included: 1) Not acknowledging the legitimacy of scientific evidence regarding the families of critically ill patients; 2) Imbalanced power relationships among the members of multi-disciplinary teams; 3) Nurses' lack of involvement in information flow; 4) The organization of time and physical space in the unit. Factors facilitating change: 1) A sense of individual and shared commitment; 2) Leadership in day-to day matters; 3) A process based on reflection. CONCLUSIONS: A process of participatory action research can lead to change in clinical practice, although this is complex and requires substantial input in terms of personal energy. Contextual factors limiting this change are related to the actual structure of the unit, while factors facilitating it are circumstantial ones and are dependent upon individual people. In this sense, professionals working at the bedside are capable of introducing changes to the context in which they work. PMID- 22300884 TI - Selective and slow-binding inhibition of shikonin derivatives isolated from Lithospermum erythrorhizon on glycosyl hydrolase 33 and 34 sialidases. AB - Sialidases are enzymes that catalyze the hydrolysis of sialic acid residues from various glycoconjugates, which are widely found in a number of viral and microbial pathogens. In this study, we investigated the biological evaluation of isolated six shikonins (1-6) and three shikonofurans (7-9) from Lithospermum erythrorhizon. The nine isolated compounds 1-9 showed strong and selective inhibition of glycosyl hydrolase (GH) 33 and -34 sialidases activities. In GH33 bacterial-sialidase inhibition assay, the inhibitory activities against GH33 siadliase of all shikonofuran derivatives (7-9) were greater than shikonin derivatives (1-6). Shikonofuran E (8) exhibited the most potent inhibitory activity toward GH33 sialidases (IC(50)=0.24MUM). Moreover, our detailed kinetic analysis of these species unveiled that they are all competitive and simple reversible slow-binding inhibitors. Otherwise, they showed different inhibitory capacities and kinetic modes to GH34 viral-sialidase activity. All the naphthoquinone derivatives (1-6) were of almost equal efficiency with IC(50) value of 40MUM and shikonofurans (7-9) did not show the significant inhibitory effect to GH34 sialidase. Kinetic analyses indicated that naphthoquinones acted via a noncompetitive mechanism. PMID- 22300885 TI - Determining the mode of action of bioactive compounds. AB - Matching bioactive molecules with molecular targets is key to understanding their modes of action (MOA). Moving beyond the mere discovery of drugs, investigators are now just beginning to integrate both biochemical and chemical-genetic approaches for MOA studies. Beginning with simple screens for changes in cell phenotype upon drug treatment, drug bioactivity has been traditionally explored with affinity chromatography, radiolabeling, and cell-based affinity tagging procedures. However, such approaches can present an oversimplified view of MOA, especially in light of the recent realization of the extent of polypharmacology and the unexpected complexity of drug-target interactions. With the advent of more sophisticated tools for genetic manipulation, a flood of powerful techniques has been used to create characteristic drug MOA 'fingerprints'. In particular, whole genome expression profiling and deletion and overexpression libraries have greatly enhanced our understanding of bioactive compounds in vivo. Here we highlight challenges and advances in studying bioactive compound-target interactions. PMID- 22300886 TI - Synthesis, molecular docking and biological evaluation of 1,3,4-oxadiazole derivatives as potential immunosuppressive agents. AB - A series of novel 1,3,4-oxadiazole derivatives (5a-5s) have been designed, synthesized and evaluated for their immunosuppressive activity. Most of these synthesized compounds were proved to have potent immunosuppressive activity and low toxicity. Among them, compounds (5m-5r) showed the most potent biological activity against lymph node cells. The results of flow cytometry (FCM) and western blotting demonstrated that compound 5q induce cell apoptosis by the inhibition of PI3K/AKT pathway. Molecular docking was performed to position compound 5q into PI3Kgamma binding site in order to explore the potential target. PMID- 22300887 TI - QSAR study and synthesis of new phenyltropanes as ligands of the dopamine transporter (DAT). AB - The dopamine transporter (DAT) plays a pivotal role in the regulation of dopamine neurotransmission, and is involved in a number of physiological functions and brain disorders. Furthermore the DAT analysis by molecular imaging techniques is a useful tool for the diagnosis and follow up treatment of diseases involving the DAT. In order to predict the affinity of new derivatives for the DAT, different QSAR molecular modeling models based on cocaine were compared. We have evaluated in these models tropane derivatives synthesized with original synthons which coupled properties of both fluorine and iodine atoms. One compound showed a high in vitro affinity and selectivity for the DAT (K(i)=0.87+/-0.04 nM). This compound should be radiolabeled with radioiodine for further investigations by SPECT. PMID- 22300888 TI - Redox potentials, laccase oxidation, and antilarval activities of substituted phenols. AB - Laccases are copper-containing oxidases that are involved in sclerotization of the cuticle of mosquitoes and other insects. Oxidation of exogenous compounds by insect laccases may have the potential to produce reactive species toxic to insects. We investigated two classes of substituted phenolic compounds, halogenated di- and trihydroxybenzenes and substituted di-tert-butylphenols, on redox potential, oxidation by laccase and effects on mosquito larval growth. An inverse correlation between the oxidation potentials and laccase activity of halogenated hydroxybenzenes was found. Substituted di-tert-butylphenols however were found to impact mosquito larval growth and survival. In particular, 2,4-di tert-butyl-6-(3-methyl-2-butenyl)phenol (15) caused greater than 98% mortality of Anophelesgambiae larvae in a concentration of 180nM, whereas 2-(3,5-di-tert-butyl 4-hydroxyphenyl)-2-methylpropanal oxime (13) and 6,8-di-tert-butyl-2,2-dimethyl 3,4-dihydro-2H-chromene (33) caused 93% and 92% mortalities in concentrations of 3.4 and 3.7MUM, respectively. Larvae treated with di-tert-butylphenolic compounds died just before pupation. PMID- 22300889 TI - Surgical treatment of unruptured intracranial aneurysms in a low-volume hospital- outcome and review of literature. AB - BACKGROUND: The aim of this study was to evaluate surgical outcome of unruptured intracranial aneurysms (UIAs) in a low-volume hospital and compare the results with the recent literature. METHODS: A retrospective review of all consecutive craniotomies for UIA from July 1999 through June 2009 was performed. Morbidity was defined as modified Rankin Scale (mRS) >= 3 and evaluated six weeks after surgery. Cognitive function was evaluated at rehabilitation-to-home discharge. A PubMed database search (2001-2011) seeking retrospective, single-center studies reporting on surgical outcome of UIAs was performed. RESULTS: There were 47 procedures performed in 42 patients to treat 50 UIAs (mean of 5 annual craniotomies). The mean age was 54.7 +/- 12.1 years and mean aneurysm size was 7.6 +/- 4.0mm. Favorable outcome (mRS 0-2) at six weeks after surgery was achieved in 45 of 47 procedures (95.7%). Aneurysm size >= 12 mm was statistically significant related to adverse outcome defined as mRS change >= 1 (71% vs. 29%; p = 0.018). Five patients (10.6%) with favorable neurological outcome (mRS 2) presented with cognitive impairment at rehabilitation-to-home discharge. There was no significant difference in overall morbidity and mortality comparing low- and high-volume hospitals (4.0% vs. 4.8%; p = 0.85). CONCLUSIONS: Low-volume hospitals may achieve good results for surgical treatment of UIAs. The results indicate that defining numeric operative volume thresholds is not feasible to guide centralization of aneurysm treatment. PMID- 22300890 TI - Restorative neurology: consideration of the new anatomy and physiology of the injured nervous system. AB - The adult human nervous system is an incredibly complex set of thousands to tens of thousands of connections between a hundred billion neurons that develops via an intricate spatial-temporal process and is shaped by experience. In addition, any one anatomical arrangement of neural circuits is usually capable of multiple physiological states. Following neurological injury, a new anatomy, and consequently a new spectrum of physiology, emerges within this nervous system with its mix of both injured and uninjured parts. It is this new combination of neural components that determines the extent to which natural functional recovery can occur and the extent to which clinical interventions can further that recovery. Detecting the new anatomy and physiology of the injured human nervous system is difficult but not impossible and some methods can track over time changes in neural structure or, more often, functions that correlate with neurological improvement. The goal of restorative neurology is to make best use of this new anatomy and physiology to facilitate neurological recovery. While we are still learning about how neurorehabilitation interventions generate functional recovery, we can begin to test hypothesis regarding the underlying mechanisms of neural plasticity and attempt to augment those processes. PMID- 22300891 TI - The androgen receptor. PMID- 22300892 TI - Continuous interferon-alpha2b infusion in combination with ribavirin for chronic hepatitis C in treatment-experienced patients. AB - BACKGROUND: Sustained virological response (SVR) rates in previous non-responders to pegylated interferon (PEG-IFN)-alpha and ribavirin for chronic HCV remain low (~10%). We hypothesize that continuous subcutaneous delivery of fully potent interferon (IFN)-alpha2b via an external pump will lead to stable blood concentrations and thereby prevent subtherapeutic trough levels associated with viral breakthrough. The aims of the study were to assess safety, tolerability and virological response in patients who were previous PEG-IFN-alpha/ribavirin non responders. METHODS: We randomized 30 HCV genotype 1 (n=24) and genotype 4 (n=6) patients to receive 6, 9 or 12 million units (MU) IFN-alpha2b daily by continuous subcutaneous administration using an insulin pump (MiniMed((r)) 508; Medtronic Inc., Minneapolis, MN, USA) in combination with ribavirin (1,000-1,600 mg) for 48 weeks. RESULTS: The magnitude of viral decline in the 12 MU group after 4 weeks of treatment was 2.67 log HCV RNA compared with 1.21 and 1.27 log HCV RNA in the 9 and 6 MU groups, respectively (P=0.001). In the intention-to-treat analysis, the SVR rate was 20% (6/30). The per-protocol SVR rate was 25% (6/24), of which four out of six patients in the high-dose arm achieved SVR. Adverse events appeared dose-dependent, were mostly mild-to-moderate and were typical of IFN therapy. Five patients developed irritation and/or abscesses at the injection site. Six serious adverse events were reported in five patients. CONCLUSIONS: Continuous delivery of IFN-alpha2b can induce a strong dose-dependent viral suppression. This could be an effective approach in conjunction with, or as lead in therapy prior to, treatment with a direct antiviral agent. PMID- 22300893 TI - A practical review of the Glasgow Coma Scale and Score. AB - Since the Glasgow Coma Scale was introduced in 1974,(1) it has become the most common method of describing a patient's level of consciousness. However, despite its almost universal use, there remain a number of misunderstandings, particularly regarding the appropriate situations in which to use the Glasgow Coma Score rather than the Scale, and also in the correct way to elicit and record the motor responses. This article, aimed at non-neurosurgeons, addresses these problems, and provides a reference for those wishing to learn or teach the Glasgow Coma Scale and Score. PMID- 22300894 TI - Implementation of an antibiotic prophylaxis protocol in an intensive care unit. AB - BACKGROUND: When properly employed, the prophylactic use of antimicrobials is associated with a reduction in surgical site infections (SSIs). We found that the appropriate use of antimicrobial prophylaxis was only 50.5% (53/105) among patients undergoing surgery in the adult intensive care unit of our hospital. In 2001, a protocol was designed to improve compliance with recommended practice. METHODS: We used a prospective interventional study and a case control study carried out between 2001 and 2007, including follow-up and daily intervention to improve compliance with antimicrobial prophylaxis guidelines and to monitor antimicrobial consumption and SSI rates. Cases of noncompliance to the prophylaxis protocol (group I) were matched to controls (group II) with appropriate prophylaxis and compared with regards to type of surgery, operative duration, intraoperative antimicrobial use, type of antimicrobial used, length of hospital stay, severity of illness, comorbidities, invasive devices, possible adverse reactions, and death. RESULTS: Compliance with antimicrobial prophylaxis metrics reached 85%; however, we were unable to detect a change in SSI rate or consumption and cost of antimicrobials. Inappropriate use was not associated with higher likelihood of death. There were no other significant differences between the 2 groups. CONCLUSION: Our intervention increased compliance with appropriate antimicrobial surgical prophylaxis with no negative impact on patient safety. PMID- 22300895 TI - An expert panel report of a proposed scientific model demonstrating the effectiveness of antibacterial handwash products. AB - In 2005, a US Food and Drug Administration Nonprescription Drug Advisory Committee (NDAC) review of consumer antiseptic handwash product studies concluded that the data regarding existing products failed to demonstrate any association between specific log reductions of bacteria achieved by antiseptic handwashing and reduction of infection. The NDAC recommended that consumer antibacterial handwashing products should demonstrate a reduction in infection compared with non-antibacterial handwash products. In response to the NDAC review, a consumer product industry-sponsored expert panel meeting was held in October 2007 to review new methods for assessing the efficacy of antibacterial handwashes. The expert panel reviewed a newly proposed model for linking the effectiveness of antibacterial handwashing to infection reduction and made recommendations for conducting future studies designed to demonstrate the efficacy of antibacterial handwash formulations. The panel concluded that using the surrogate infection model to demonstrate efficacy has a sound scientific basis, that the use of Shigella flexneri as a test organism coupled with a modified hand contamination procedure is supported by published data, and that the model represents a realistic test for the efficacy of consumer antibacterial handwash products. This article summarizes the expert panel's deliberations, conclusions, and recommendations. PMID- 22300896 TI - Role of phospholipase A2 pathway in regulating activation of Bufo arenarum oocytes. AB - Transient increases in the concentration of cytosolic Ca(2+) are essential for triggering egg activation events. Increased Ca(2+) results from its rapid release from intracellular stores, mainly mediated by one or both intracellular calcium channels: the inositol trisphosphate receptor (IP3R) and the ryanodine receptor (RyR). Several regulatory pathways that tailor the response of these channels to the specific cell type have been proposed. Among its many modulatory actions, calcium can serve as an activator of a cytosolic phospholipase A(2) (cPLA2), which releases arachidonic acid from phospholipids of the endoplasmic reticulum as well as from the nuclear envelope. Previous studies have suggested that arachidonic acid and/or its metabolites were able to modulate the activity of several ion channels. Based on these findings, we have studied the participation of the phospholipase A(2) (PLA(2)) pathway in the process of Bufo arenarum oocyte activation and the interrelation between any of its metabolites and the ion channels involved in the calcium release from the intracellular reservoirs at fertilization. We found that addition of both melittin, a potent PLA(2) activator, and arachidonic acid, the main PLA(2) reaction metabolite, was able to induce activation events in a bell-shaped manner. Differential regulation of IP3Rs and RyRs by arachidonic acid and its products could explain melittin and arachidonic acid behaviour in Bufo arenarum egg activation. The concerted action of arachidonic acid and/or its metabolites could provide controlled mobilization of calcium from intracellular reservoirs and useful tools for understanding calcium homeostasis in eggs that express both types of receptors. PMID- 22300897 TI - TRPM2 channel protective properties of N-acetylcysteine on cytosolic glutathione depletion dependent oxidative stress and Ca2+ influx in rat dorsal root ganglion. AB - N-acetylcysteine (NAC) is a thiol-containing (sulphydryl donor) antioxidant, which contributes to regeneration of glutathione (GSH) and also acts through a direct reaction with free radicals. Thiol depletion has been implicated in the neurobiology of sensory neurons and pain. We reported recently an activator role of intracellular GSH depletion on calcium influx through transient receptor potential melastatin-like 2 (TRPM2) channels in rat dorsal root ganglion (DRG). NAC may have a protective role on calcium influx through regulation of TRPM2 channels in the neurons. Therefore, we tested the effects of NAC on TRPM2 channel currents in cytosolic GSH depleted DRG in rats. DRG neurons were freshly isolated from rats and the neurons were incubated for 24 h with buthionine sulfoximine (BSO). In whole-cell patch clamp experiments, TRPM2 currents in the DRG incubated with BSO were gated by H(2)O(2). TRPM2 channels current densities, cytosolic free Ca(2+) content, and lipid peroxidation values in the neurons were higher in H(2)O(2) and BSO + H(2)O(2) group than in controls; however GSH and GSH peroxidase (GSH-Px) values were decreased. BSO + H(2)O(2)-induced TRPM2 channel gating was totally inhibited by extracellular NAC and partially inhibited by 2 aminoethyl diphenylborinate. GSH-Px activity, lipid peroxidation and GSH levels in the DRG neurons were also modulated by NAC. In conclusion, we observed a modulator role of NAC on Ca(2+) influx through a TRPM2 channel in intracellular GSH depleted DRG neurons. NAC incubation before BSO exposure appears to be more protective than NAC incubation after BSO exposure. Since cytosolic thiol group depletion is a common feature of neuropathic pain, our findings are relevant to the etiology and treatment of pain neuropathology in DRG neurons. PMID- 22300898 TI - Facile construction of functional biosurface via SI-ATRP and "click glycosylation". AB - Construction of high density glycosylated surfaces is important in the investigation of interactions between pathogens and surface carbohydrates. In this work, we provided a flexible method for glycosyl surface fabrication by combination of surface-initiated atom transfer radical polymerization (SI-ATRP) and copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reaction. Through this strategy, we got a very high surface glycosyl density of about 4 nmol/cm(2) with the surface "click" efficiency of nearly 50%. Then the carbohydrate decorated surfaces were used to mimic cell surfaces and specific recognition of mannose with Escherichia coli was observed. We believe the methodology provided here can be used as a facile way for construction of a wide range of functional biosurfaces. PMID- 22300899 TI - Zwitterionic lipid (DPPC)-protein (BSA) complexes at the air-water interface. AB - Complexation of zwitterionic lipid, dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and protein, bovine serum albumin (BSA) at the air-water interface has been studied by surface pressure (pi) - mean molecular area (A) isotherms and X ray reflectivity. Although BSA has isoelectric point nearly at pH~4.8, possibility of complex formation with lipid molecules has been investigated from low (~4.0) to high (~9.0) pH range in presence of divalent cation, Ca(2+) in the water subphase. Both the isotherm and reflectivity analysis show that the interaction of BSA with lipid monolayer takes place from that low to high subphase pH range, i.e., complexation occurs both below and above of the isoelectric point. Only one layer of BSA forms below the lipid monolayer and the probable reasons for such complex formation have been proposed. PMID- 22300900 TI - The economic cost of chronic noncancer pain in Ireland: results from the PRIME study, part 2. AB - To assess the economic cost of chronic pain in Ireland, information was gathered from 140 people with chronic pain. Direct and indirect costs attributable to chronic pain and medical conditions of which chronic pain was a feature were recorded retrospectively for 12 months. Mean cost per chronic pain patient was estimated at ?5,665 per year across all grades of pain, with mean costs increasing according to the severity of pain. A small proportion of patients account for the bulk of costs-the top 5% most expensive patients accounted for 26.4% of costs, with a mean cost per patient of ?29,936, and the 10% most expensive patients were responsible for 42.8% of all costs. Total cost for individuals aged 20 and above was estimated at ?5.34 billion per year, or 2.86% of Irish GDP in 2008. Those with clinically elevated depression scores had costs that were twice as high as people who scored below the depression cut-off score. Chronic pain services in Ireland are generally underresourced. Improved coordination and better management of patients via interdisciplinary pain rehabilitation program is essential and may offer a means of reducing the sizeable economic burden of chronic pain. PERSPECTIVE: The cost of chronic pain per patient was ?5,665 per year extrapolated to ?5.34 billion or 2.86% of GDP per year. Those with clinically significant depression had costs twice as high as those without depression. The significant burden of chronic pain highlights the need for cost effective interventions to reduce long-term disability. PMID- 22300901 TI - A cytokine study of adult patients with obsessive-compulsive disorder. AB - OBJECTIVES: We aimed to determine the plasma levels of cytokines in patients with obsessive-compulsive disorder (OCD) as compared with healthy controls and to investigate whether there is any association between their concentrations and OCD clinical and therapeutic features. METHODS: Forty patients with OCD and 40 healthy controls had their plasmas assessed for a range of cytokines (tumor necrosis factor-alpha, or TNF-alpha), chemokines (CCL2, CCL3, CCL11, CCL24, CXCL8, CXCL9, CXCL10), and other mediators (TNF soluble receptors sTNFR1 and sTNFR2 and interleukin-1 receptor antagonist) by enzyme-linked immunosorbent assay. Patients with OCD were further examined with the Mini-International Neuropsychiatric Interview, the Obsessive-Compulsive Inventory-Revised, and the Beck Depression Inventory. RESULTS: Compared with healthy controls, patients with OCD exhibited significantly increased plasma levels of CCL3, CXCL8, sTNFR1, and sTNFR2. Among patients with OCD, there was a positive correlation between relative antidepressant dose and sTNFr2 levels. Furthermore, although the levels of sTNFR1 correlated positively with the severity of washing symptoms, CCL24 levels correlated negatively with the severity of hoarding. CONCLUSIONS: The levels of certain immune markers are increased in adult patients with OCD and seem to vary according to predominant symptoms dimensions. Other studies are required to establish whether our findings truly reflect immunologic dysfunction in OCD or are the result of other hidden confounding factors. PMID- 22300902 TI - Symptom-specific attentional bias to threatening stimuli in obsessive-compulsive disorder. AB - OBJECTIVE: There is mixed evidence as to whether patients with obsessive compulsive disorder (OCD) have excessive attentional engagement and emotional response to OCD-related stimuli in the environment. Here we investigate the occurrence of an attentional bias toward specific OCD-related stimuli and its relationship with obsessive-compulsive symptom dimensions. METHODS: Forty-eight patients with OCD participated in an attentional bias task containing OCD- and non-OCD-related stimuli and had their performance compared with that of 24 age-, sex-, and education-matched healthy control subjects. Severity of obsessive compulsive and comorbid depressive symptoms was assessed using the Obsessive Compulsive Inventory-Revised and the Beck Depression Inventory, respectively. RESULTS: Although there were significant and almost significant group effects on the reaction time (RT) toward OCD- and non-OCD-related figures, respectively, no difference between patients with OCD and controls was noted with regard to RT toward OCD-related figures minus RT toward non-OCD-related figures. Nevertheless, within the OCD group, partial correlational analysis controlled for age and severity of depression unveiled positive correlations between (1) obsessional symptoms and RT toward checking-related pictures and (2) ordering symptoms and RT toward ordering-related pictures. CONCLUSIONS: The positive correlations between RT to content-specific stimuli and the severity of corresponding obsessive compulsive symptoms suggest that patients with OCD experience difficulty in disengaging attention from personally salient stimuli. PMID- 22300903 TI - Gambling on the stock market: an unexplored issue. AB - OBJECTIVE: Stock market investment (SMI) is one of the most socially acceptable types of gambling, which, however, can turn into a gambling problem. Because it is barely examined, we compared a series of clinical, psychopathologic, and personality variables in SMI gambling patients (both as primary and secondary problem) with a group of traditional pathologic gamblers (PGs). METHOD: A total sample of 1470 PGs (1376 patients without SMIs [PG-SMI], 76 patients with SMI as a secondary gambling problem [PG+SMI], and 18 patients with SMI as a primary gambling problem [SMI+PG]) participated in this study. All participants were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. The following instruments were used: the South Oaks Gambling Screen, the Symptom Check List-90 Items-Revised, the Temperament and Character Inventory-Revised, and other clinical and psychopathologic indices. RESULTS: The 3 patient groups' profiles were statistically similar in psychometrical measures. The risk of having SMI increased for patients with higher education, and the presence of SMI as a primary problem in PGs increased with university study level and higher scores on the personality trait of cooperativeness. CONCLUSIONS: The results of this study indicate comparability of SMI gamblers with PGs in their general clinical profile and in psychopathology and personality. PMID- 22300904 TI - Borderline personality disorder in adolescents: evidence in support of the Childhood Interview for DSM-IV Borderline Personality Disorder in a sample of adolescent inpatients. AB - Empirical evidence is increasing in support of the validity of the construct of borderline personality disorder (BPD) in adolescence. There is growing consensus that the early identification and treatment of emerging borderline traits may be an important focus. However, few diagnostic (questionnaire- or interview-based) measures specifically developed or adapted for adolescents and children exist. The Childhood Interview for DSM-IV Borderline Personality Disorder (CI-BPD) [Zanarini, 2003] is a promising interview-based measure of adolescent BPD. Currently, no studies have explicitly been designed to examine the psychometric properties of the CI-BPD. The aim of the current study was to examine various psychometric properties of the CI-BPD in an inpatient sample of adolescents (n = 245). A confirmatory factor analytic approach was used to examine the internal factor structure of the 9 CI-BPD items. In addition, internal consistency, interrater reliability, convergent validity (with clinician diagnosis and 2 questionnaire-based measures of BPD), and concurrent validity (with Axis I psychopathology and deliberate self-harm) were examined. Similar to several adult studies, the confirmatory factor analytic results supported a unidimensional factor structure for the CI-BPD, indicating that the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria on which the CI-BPD is based constitute a coherent combination of traits and symptoms even in adolescents. In addition, other validity criteria were excellent. Taken together, the current study provides strong evidence for the validity of the CI-BPD for use in adolescents. PMID- 22300905 TI - Cognitive impairment in school-aged children with early trauma. AB - Exposure to traumatic events during childhood is often associated with the development of psychiatric disorders, cognitive impairment, and poor functioning in adulthood. However, few studies have examined cognitive function, including executive function, memory, and attention, in school-aged children with early trauma compared with age- and sex-matched controls. We recruited 30 medication naive children between 5 and 12 years of age with a history of early severe trauma from a foster care home, along with 30 age- and sex-matched controls. Psychiatric diagnoses were based on Kiddie Schedule for Affective Disorders and Schizophrenia Epidemiologic Version (K-SADS-E) for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and were confirmed with a clinical interview. The neuropsychologic battery was tailored to assess broad cognitive domains such as learning/working memory, executive function, attention, verbal/premorbid intellectual functioning, and impulsivity. There was a higher prevalence of subsyndromal symptoms in children with a history of childhood trauma, although they rarely met all of the diagnostic criteria for a disorder. Moreover, lower estimated intellectual functioning scores were associated with subsyndromal symptoms in children with a history of trauma, and they performed more poorly on the Digits Span Test of the Wechsler Intelligence Scale for Children-III Edition, suggesting attention impairment. There is a high prevalence of subsyndromal symptoms in school-aged children with trauma and an attention impairment, which may contribute to a cumulative deficit early in cognitive development. These findings further support the need for early interventions that can prevent cognitive impairment when childhood trauma occurs. PMID- 22300906 TI - ICH guidance in practice: degradation behaviour of oseltamivir phosphate under stress conditions. AB - Oseltamivir phosphate was subjected to stress degradation conditions prescribed by ICH guideline Q1A (R2). A total of five degradation products (Os I to Os V) were generated under hydrolytic (acid and alkaline) stress conditions. Their unambiguous structural elucidation was carried out using LC-MS, LC-NMR and HR-NMR data. First, accurate masses of Os I, Os II, Os IV and Os V were determined by LC MS/TOF. Subsequently, (1)H and COSY NMR studies were carried on the drug and these four degradation products using LC-NMR. The structure of Os III was elucidated after preparative isolation and purification, followed by MS/TOF and HR-NMR studies. The degradation products, Os II, Os IV and Os V were characterized as 4-acetamido-5-amino-3-(pentan-3-yloxy)cyclohex-1-ene carboxylic acid, 4,5-diamino-3-(pentan-3-yloxy)cyclohex-1-ene carboxylic acid and ethyl 4,5 diamino-3-(pentan-3-yloxy)cyclohex-1-ene carboxylate, respectively. Os I and Os III were identified as positional isomers of Os II and the drug, respectively, involving N,N-acyl migration from 4-amino to 5-amino position in the ring. Two degradation products (Os IV and Os V) were found to be new and previously unreported. The degradation pathway for all five was outlined and justified mechanistically. In silico toxicity of the drug and degradation products was also assessed using TOPKAT and DEREK software and compared. PMID- 22300907 TI - Evaluation of inhibition of cancer cell proliferation in vitro with different berries and correlation with their antioxidant levels by advanced analytical methods. AB - Dimethylsulfoxide extracts of Chilean berries [Myrteola nummularia, 'Murtilla like'] vs. well known 'Murtilla', Chilean and Polish blueberries, and Chilean raspberries were investigated for their antioxidant, quenching and antiproliferative activities. The significantly highest levels of polyphenols, flavonoids, flavanols and their antioxidant activities were estimated in 'Murtilla' (MT) berries (P<0.05), than in other investigated samples. DPPH kinetic measurements were calculated to compare, distinguish and discriminate the antiradical activity among berry extracts by multivariate analysis. The lowest IC(50) values, 751 and 858 MUg/ml, were obtained for MT extract on colon cancer cell lines HT-29 and SW48. HT-29 cells treated with MT extract showed a decrease in G1 phase cells from 77% to 56% (P<0.05). At the highest concentration of 2000 MUg/ml MT extract caused 90-100% cell growth inhibition. Percentage of death cells treated with MT extract was 80.1% and 72.5% for SW48 and HT-29 cells, respectively. The inhibition of cancer cell proliferation highly correlated with the levels of polyphenols, flavonoids and their antioxidant activities. The interaction between drugs and serum albumin plays an important role in the distribution and metabolism of drugs, therefore the complexation reaction between flavonoids, and berries extracts, and bovine serum albumin (BSA) was investigated by 3-D fluorescence and FTIR spectroscopy. The results indicated that flavonoids and polyphenol extracts have strong ability to quench the intrinsic fluorescence of BSA by forming complexes. A shift in the maximum of amides FTIR-bands appeared. In conclusion, these findings suggest that the intake of a new kind of berry, as a source of natural antioxidants, may reduce colon cancer risk. PMID- 22300908 TI - An improved simple LC-MS/MS method for the measurement of serum aripiprazole and its major metabolite. AB - BACKGROUND AND OBJECTIVES: Current liquid chromatographic tandem mass spectrometry (LC-MS/MS) methods to measure serum levels of aripiprazole (Ar) and dehydroaripiprazole (DHAr) are sensitive, but difficult to use in a hospital context. We aimed to develop a rapid LC-MS/MS method allowing reliable level measurement in the presence of co-administered drugs, withdrawing samples from 22 patients with acute agitation receiving 9.75 mg aripiprazole IM injection. METHOD: We developed a sensitive and selective HPLC-MS/MS method to measure serum Ar and DHAr levels in a hospital laboratory, requiring minimal sample preparation and inferior sample volume compared to previous LC-MS/MS methods. Analytes were separated on a reversed-phase HPLC (run-time, 10 min). A triple quadrupole tandem mass spectrometer was used for quantitative analysis in positive mode by a multiple reaction monitoring. Samples were drawn 2, 4, 6, and 24h post-injection. RESULTS: Calibration curves (2-1000 ng/mL for Ar and 3.5-500 ng/mL for DHAr) were linear, with mean correlation coefficient >0.9998. Within- and between-day precision and accuracy were within 10%. Mean recovery was 95.2 +/- 4.5% for Ar and 97.6 +/- 7.2% for DHAr. Ar and DHAr peaks were not affected by other co administered psychotropic drugs. CONCLUSION: Our method measured Ar and DHAr concentrations reliably, simply and rapidly without employing many reagents, as currently existing methods. PMID- 22300909 TI - Determination of maternal-fetal biomarkers of prenatal exposure to ethanol: a review. AB - The deleterious effects exerted by prenatal ethanol exposure include physical, mental, behavioural and/or learning disabilities that are included in the term fetal alcohol spectrum disorder (FASD). Objective assessment of exposure to ethanol at both prenatal and postnatal stages is essential for early prevention and intervention. Since pregnant women tend to underreport alcohol drinking by questionnaires, a number of biological markers have been proposed and evaluated for their capability to highlight gestational drinking behaviour. These biomarkers include classical biomarkers (albeit indirect) of alcohol-induced pathology (mean corpuscular volume (MCV), gamma glutamyltransferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) acetaldehyde derived conjugates, and finally derivatives of non-oxidative ethanol metabolism (fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG), ethyl sulphate (EtS) and phosphaditylethanol (PEth)). Since ethanol itself and acetaldehyde are only measured few hours after ethanol intake in conventional matrices such as blood, urine and sweat, they are only useful to detect recent ethanol exposure. In the past few years, the non-oxidative ethanol metabolites have received increasing attention because of their specificity and in some case wide time-window of detection in non-conventional matrices from the pregnant mother (oral fluid and hair) and fetus-newborn (neonatal hair, meconium, placenta and umbilical cord). This article reviews bioanalytical procedures for the determination of these markers of ethanol consumption during pregnancy and related prenatal exposure. In addition, clinical toxicological applications of these procedures are presented and discussed. PMID- 22300910 TI - The economic burden of child maltreatment in the United States and implications for prevention. AB - OBJECTIVES: To present new estimates of the average lifetime costs per child maltreatment victim and aggregate lifetime costs for all new child maltreatment cases incurred in 2008 using an incidence-based approach. METHODS: This study used the best available secondary data to develop cost per case estimates. For each cost category, the paper used attributable costs whenever possible. For those categories that attributable cost data were not available, costs were estimated as the product of incremental effect of child maltreatment on a specific outcome multiplied by the estimated cost associated with that outcome. The estimate of the aggregate lifetime cost of child maltreatment in 2008 was obtained by multiplying per-victim lifetime cost estimates by the estimated cases of new child maltreatment in 2008. RESULTS: The estimated average lifetime cost per victim of nonfatal child maltreatment is $210,012 in 2010 dollars, including $32,648 in childhood health care costs; $10,530 in adult medical costs; $144,360 in productivity losses; $7,728 in child welfare costs; $6,747 in criminal justice costs; and $7,999 in special education costs. The estimated average lifetime cost per death is $1,272,900, including $14,100 in medical costs and $1,258,800 in productivity losses. The total lifetime economic burden resulting from new cases of fatal and nonfatal child maltreatment in the United States in 2008 is approximately $124 billion. In sensitivity analysis, the total burden is estimated to be as large as $585 billion. CONCLUSIONS: Compared with other health problems, the burden of child maltreatment is substantial, indicating the importance of prevention efforts to address the high prevalence of child maltreatment. PMID- 22300911 TI - Prospets of stem cell research and regeneration medicine. PMID- 22300912 TI - The arresting phase determines the total healing time of a locally irradiated skin wound in swine. AB - OBJECTIVE: Radiation is an important cause of delayed wound healing, and there still exist many questions regarding the patterns and mechanisms of wound healing. This study investigated the characteristics of wound healing after varying doses of local radiation and explored possible causes of the delay in healing caused by radiation. METHODS: A full-thickness dorsal longitudinal skin tissue, 2 cm in diameter, was excised after local irradiation on one side of the back of swine, and the other side was wounded as a control. The size of the wound area was recorded every two days after injury. Pathological changes, proliferating cell nuclear antigen (PCNA, immunohisto- chemistry) and apoptosis levels (TUNEL assay) were measured at different time points after wounding. RESULTS: The course of wound healing can be divided into four phases, namely: the arresting phase, the healing priming phase, the fast healing phase, and the healed phase. Although the total wound healing time was closely correlated to the dose of irradiation (R(2) equal to 0.9758), it was more dependent on the length of the arresting phase (R(2) equal to 0.9903) because once the arresting phase ended, the wound healed at a similar speed regardless of radiation doses. Pathological analysis showed that compared with the control side there were more necrotic tissues, slower epithelial crawling, as well as fewer blood vessels and cellular components in the irradiated side at the arresting phase, while other phases revealed no significant difference concerning these measurements. Immunohistochemistry showed that the irradiated wounds had significantly less PCNA-positive and more TUNEL-positive labeling of cells in the arresting phase than in other phases. Moreover, the changes were positively related to the radiation doses, but there was no obvious difference in cell proliferation or apoptosis among the healing priming phase, fast healing phase or healed phase, whether on the control side or on the irradiated side. CONCLUSIONS: After local irradiation, the length of the arresting phase determines the wound healing time. Increased apoptosis and decreased cell proliferation might be an important reason for the formation of the arresting phase. PMID- 22300913 TI - One-stage apertura thoracis superior approach for four-vessel occlusion in rats. AB - OBJECTIVE: There are a great number of modified models based on the four-vessel occlusion (4VO) model of Pulsinelli and Brierley which has been used worldwide for brain ischemia research. However, up to now the problems of collateral circulations of 4VO and the difficulty in arranging a surgery to occlude the basilar artery in other models are not satisfactorily solved yet. In this study, an improved 4-vessel occlusion (I4VO) rat model which is easy to handle and able to decrease the effect of collateral circulation is reported. METHODS: The common carotid arteries and the beginning of the subclavical arteries of rats were occluded for different time by one-stage apertura thoracis superior approach. Neurological deficit scores defined by the modified Garcia scoring system and histopathological method were used to evaluate the effects of this model up to 7 days after reperfusion. RESULTS: The neurological scores in the 15-min and 25-min groups decreased significantly at 24, 48 and 72 hours after reperfusion (P less than 0.05), and the histopathologic study showed that there were stable, symmetrical changes of lesions in bilateral hippocampus in all the ischemia samples from two ischemia groups compared with sham operated group (P less than 0.05). CONCLUSION: This modified model is safe, easy, reliable, stable, mini invasive as well as time-saving in making bilateral hemispheric ischemia, which can effectively decrease collateral circulations and meanwhile lead to stable lesions in hippocampus and cortex. PMID- 22300914 TI - Is management of acute traumatic brain injury effective? A literature review of published Cochrane Systematic Reviews. AB - OBJECTIVE: To evaluate all the possible therapeutic measures concerning the acute management of traumatic brain injury (TBI) mentioned in Cochrane Systematic Reviews published in the Cochrane Database of Systematic Reviews (CDSR). METHODS: An exhausted literature search for all published Cochrane Systematic Reviews discussing therapeutic rather than prevention or rehabilitative interventions of TBI was conducted. We retrieved such databases as CDSR and Cochrane Injury Group, excluded the duplications, and eventually obtained 20 results, which stand for critical appraisal for as many as 20 different measures for TBI patients. The important data of each systematic review, including total population, intervention, outcome, etc, were collected and presented in a designed table. Besides, we also tried to find out the possible weakness of these clinical trials included in each review. RESULTS: Analysis of these reviews yielded meanfuling observations: (1) The effectiveness of most ordinary treatments in TBI is inconclusive except that corticosteroids are likely to be ineffective or harmful, and tranexamic acid, nimodipine and progesterone show a promising effect in bleeding trauma, traumatic subarachnoid hemorrhage, TBI or severe TBI. (2) A majority of the systematic reviews include a small number of clinical trials and the modest numbers of patients, largely due to the uncertainty of the effectiveness. (3) The quality of most trials reported in the systematic reviews is more or less questionable. (4) In addition, lots of other complex factors together may lead to the inconclusive results demonstrated in the Cochrane Systematic Reviews. CONCLUSIONS: For clinical physicians, to translate these conclusions into practice with caution is essential. Basic medication and nursing care deserve additional attention as well and can be beneficial. For researchers, high quality trials with perfect design and comprehensive consideration of various factors are urgently required. PMID- 22300915 TI - Posterior malleolar fracture: technique and clinical experience of the posterolateral approach. AB - OBJECTIVE: To introduce the postero- lateral surgical approach to the posterior malleolar fracture and report its clinical outcomes in 32 cases. METHODS: This study consisted of 32 cases, 22 males and 10 females with the mean age of 48 years (range, 21-63 years), suffering from posterior malleolar fracture. All cases were treated with the posterolateral surgical approach to the ankle. The average follow-up period was 28 months (range, 24-35 months). The clinical outcomes of these cases were evaluated on the basis of the Olerud-Molander Ankle (OMA) score and plain radiographs. RESULTS: All cases showed radiological evidence of bony union at follow-up. The average OMA score was 82 points; 21 cases had excellent scores (90-100 points), 9 good (61-90 points), and 2 fair (31 60 points). The excellent-to-good rate was 93.8%. Although most cases did not show any wound dehiscence or necrosis, one patient had a superficial infection which healed after using antibiotic dressing and one had sural cutaneous nerve injury that underwent spontaneous remission without any treatment after three months. In addition, one presented with mild symptoms of peroneal tendonitis that disappeared after plate removal. CONCLUSION: The posterolateral approach offers an effective technique for fracture reduction and fixation of large posterior malleolar fragments. PMID- 22300916 TI - Comparative analysis of characteristics and risk factors of traffic injury in aged people from urban and rural areas in Chongqing. AB - OBJECTIVE: To study the epidemiologic characteristics of traffic injuries among people over 60 years old in the Nan'an district (urban) and Jiangjin district (rural) of Chongqing, and to discuss the corresponding strategies for its prevention and cure. METHODS: Records of traffic injuries in people over 60 years old registered by the traffic police between 2000 and 2006 in Nan'an district and Jiangjin district were collected in the Database of Road Traffic Accidents and Traffic Injuries. Epidemiologic characteristics of traffic injuries among the aged people were analyzed and compared. RESULTS: Between the year 2000 and 2006, the average annual incidence of traffic injuries and mortality rate in the aged people in Nan'an district were 124.62/100 000 and 13.85/ 100 000 respectively, higher than that in Jiangjin district (27.49/ 100 000, 7.13/100 000, P less than 0.01). However, the mortality rate for the aged people who were involved in traffic injuries in Jiangjin district was 20.60%, higher than that in Nan'an district (10.00%, P less than 0.01). Head injury was the primary cause of death. Totally 76.58% of casualties were pede-strians. Over 90% of the traffic accidents occurred in the areas with no traffic signal or traffic control system. CONCLUSIONS: The traffic environment is unfavorable to the aged people. It is important to enhance traffic safety consciousness of drivers and the elderly and to strengthen traffic safety system and traffic law, so as to provide a safe road traffic environment for the aged people. PMID- 22300917 TI - Dorsalis pedis arterialized venous flap for hand and foot reconstruction. AB - OBJECTIVE: To report the results of repair of skin defects in the extremities with arterialized venous flap harvested from the lateral aspect of the dorsum of the foot. METHODS: Six cases of skin and soft tissue defects over the foot and hands were resurfaced by free arterialized venous flaps, including five patients with skin defects of the hands, and one with defects at the dorsum of the foot. The flaps were harvested from the lateral aspect of the dorsum of the foot with the sizes ranging from 2 cm multiply 5.5 cm to 6 cm multiply 11 cm. Two veins at the proximal margin of the flap were retained, one of which was anastomosed to a recipient bed artery to provide arterial inflow and the other was anastomosed to a recipient bed vein for venous outflow. RESULTS: All flaps demonstrated mild edema and survived completely. Blisters appeared on four flaps. Using this technique, we achieved good functional and cosmetic results in this series. CONCLUSIONS: Dorsalis pedis arterialized venous flap with rich vascular communications could enhance peripheral perfusion and decrease congestion of venous flaps, thereby improves reliability and utility for extremity reconstruction. PMID- 22300918 TI - Cervical spinal canal narrowing and cervical neurological injuries. AB - Cervical spinal canal narrowing can lead to injury of the spinal cord and neurological symptoms including neck pain, headache, weakness and parasthesisas. According to previous and recent clinical researches, we investigated the geometric parameters of normal cervical spinal canal including the sagittal and transverse diameters as well as Torg ratio. The mean sagittal diameter of cervical spinal canal at C(1) to C(7) ranges from 15.33 mm to 20.46 mm, the mean transverse diameter at the same levels ranges from 24.45 mm to 27.00 mm and the mean value of Torg ratio is 0.96. With respect to narrow cervical spinal canal, the following charaterstics are found: firstly, extension of the cervical spine results in statistically significant stenosis as compared with the flexed or neutral positions; secondly, females sustain cervical spinal canal narrowing more easily than males; finally, the consistent narrowest cervical canal level is at C(4) for all ethnicity, but there is a slight variation in the sagittal diameter of cervical spinal stenosis (less than or equal to 14 mm in Whites, less than or equal to 12 mm in Japanese, less than or equal to 13.7 mm in Chinese). Narrow sagittal cervical canal diameter brings about an increased risk of neurological injuries in traumatic, degenerative and inflammatory conditions and is related with extension of cervical spine, gender, as well as ethnicity. It is hoped that this review will be helpful in diagnosing spinal cord and neurological injuries with the geometric parameters of cervical spine in the future. PMID- 22300919 TI - Causes of death after hip fracture in senile patients. AB - Hip trauma has been a leading cause of death in senile patients for more than a centenary. Although the mortality decreased due to the advanced technique in medication, surgery and nursing, the increasing mortality should not be neglected in elders after orthopedic operation nowadays. Many factors are considered to influence the causes of death after trauma, such as age, gender, personal customs, comorbidities, types of fracture, timing of surgery, procedure, anesthesia, complications, medical treatment, activity of daily living, or even marriage status. This article reviews these causes from the aspects of patient's own factors, iatrogenic factors, medical treatment and other factors and provides some clues for further clinical application according to the recent foreign and domestic researches. According to the present research, it is essential for surgeons to perform a comprehensive estimation for patients suffering from hip trauma. PMID- 22300920 TI - Rare case of impalement of two occupants of a vehicle by the same object: insights into the management of complex thoracic impalements. AB - Thoracic impalement injuries are very rare and the majority of patients do not survive to reach a medical care facility. In this case report, we describe the successful outcome of a case of double thoracic impalement by two steel tors, of which one steel tor had impaled two patients simultaneously. The case report highlights all aspects of managing such rare and complex cases right from prehospital care; extrication process which happened under controlled environment at the trauma centre itself, till the definitive management of the impaled thoracic objects. Thoracic impalement injuries are dramatic and appear very challenging. However presence of mind of the managing team, coordinated team effort and availability of adequate facilities can lead to a successful outcome. PMID- 22300921 TI - Simultaneous bilateral patellar tendon rupture without predisposing systemic disease or steroid use: a case report. AB - There is a dearth of case reports describing simultaneous bilateral patellar tendon ruptures in the medical literature. These ruptures are often associated with systemic disorders such as lupus erythematosus or chronic steroid use. The author describes a case of a 24-year-old man who sustained traumatic bilateral patellar tendon ruptures without any history of systemic disease or steroidal medication. We repaired and reattached the ruptured tendons to the patella and augmented our procedure with allogeneic tendon followed by wire loop reinforcement. One year after operation, the patient regained a satisfactory range of motion of both knees with good quadriceps strength and no extensor lag. The recurrent microtrauma from a history of intense sports activity and a high body mass index may have played an important role in this trauma event. PMID- 22300922 TI - A successful treatment of traumatic bronchobiliary fistula by endoscopic retrograde biliary drainage. AB - Bronchobiliary fistula (BBF) is a rare condition in which there is a nonnatural communication between the biliary tract and the bronchial trees. It is usually aroused by the complications of hepatic hydatidosis, hepatic amebic, biliary obstruction, trauma, neoplasm and hepatic abscess formation. In this paper, we described a patient suffering from BBF that is secondary to trauma or surgery. Especially, BBF was detected in the left lung. Finally, we managed this case successfully without an open surgery. PMID- 22300923 TI - Scapular dislocation from trivial trauma: a rare case. AB - Dislocation of the scapula between the ribs and into the thoracic cage is a very rare event. Scapulothoracic dissociation though has been reported, usually occurs after a severe injury and is often associated with other serious injuries like brachial plexus or chest injury, etc. Ainscow has described a rare type that may occur due to slight violence with a pre-existing condition. Cases of isolated scapular dislocation after minor trauma have not been reported frequently in the literature. It is a distinct clinical entity and needs to be differentiated from other similar conditions. Here, we present a case of painless scapular dislocation associated with trivial trauma followed by spontaneous reduction in a 10 years old girl. The patient had a recurrence of the dislocation before presenting to us. But she did not have any pre-existing condition for scapular dislocation. PMID- 22300924 TI - Flow-diverter silk stent for the treatment of intracranial aneurysms: 1-year follow-up in a multicenter study. AB - BACKGROUND AND PURPOSE: FD stent placement is a promising therapy for challenging intracranial aneurysms. Long-term evaluations about angiographic and morphologic results are still missing. This is the aim of this multicenter series. MATERIALS AND METHODS: We report our experience and 1-year FU in a retrospective chart review of 65 consecutive subjects with 77 unruptured or recanalized aneurysms that were treated with Silk FD stents at 6 centers in France. Both angiographic and clinical results were recorded before treatment and at 6 and 12 months after treatment. At the 12-month FU, relationships between angiographic aneurysm occlusion and shrinkage of the thrombosed aneurysm sac were evaluated. RESULTS: Stent deployment was achieved in 64 cases (98.5%) and failed in 1 case (1.5%). Seven misdeployments of the Silk stent caused the occlusion of 6 parent arteries. Overall acute/subacute procedural morbidity was 7.7%, and mortality was zero. Delayed complications were observed in 10.9% of subjects. At the 6-month FU, permanent morbidity was 7.8% and mortality was 3%. Complete occlusion occurred within 6 months in 68% of aneurysms and within 12 months after treatment in 84.5% of aneurysms. At the 12-month FU, in angiographically complete occluded aneurysms, MR imaging/CT analysis showed the complete disappearance of the thrombosed aneurysm in 30% of cases and partial shrinkage in 52%; furthermore, thrombosed aneurysms were stable in 11% of cases and enlarged in 7%. CONCLUSIONS: The Silk stent is an effective tool for the treatment of challenging aneurysms because it allows complete occlusion in most cases 1 year after treatment. Permanent morbidity was 7.8%, and mortality was 3%. PMID- 22300925 TI - Noninvasive evaluation of cerebral arteriovenous malformations by 4D-MRA for preoperative planning and postoperative follow-up in 56 patients: comparison with DSA and intraoperative findings. AB - BACKGROUND AND PURPOSE: 4D-MRA is a promising technique in the diagnosis and follow-up of cAVMs. The purpose of this study was to compare 4D-MRA in the pre- and postoperative evaluation of cAVMs with DSA or intraoperative findings as the standards of reference regarding qualitative and quantitative parameters. MATERIALS AND METHODS: Fifty-six consecutive patients with cAVMs (30 women) underwent both 4D-MRA and DSA. Preoperative 4D-MRA was excluded from analysis in 1 patient (movement artifacts). Twenty-five patients underwent surgery on cAVMs and underwent both imaging modalities pre- and postoperatively. 4D-MRA was performed with either 0.5-mol/L gadolinium-diethylene-triamine pentaacetic acid (group 1: voxel size, 1.1 * 1.1 * 1.4 mm(3); 608 ms/dynamic frame; 19 patients) or 1.0-mol/L gadobutrol (group 2: voxel size, 1.1 * 1.1 * 1.1 mm(3); 572 ms/dynamic frame; additional alternating view sharing; 37 patients). Two readers independently reviewed 4D-MRA and DSA regarding the Spetzler-Martin classification, arterial feeders, and postoperative residual filling. Vessel sharpness, vessel diameter, and VBC of 4D-MRA were quantified. RESULTS: Preoperative Spetzler-Martin classification 4D-MRA and DSA ratings matched in 55/55 patients (Spetzler-Martin grades: I, 12; II, 22; III, 15; IV, 5; V, 1), and 93/100 arterial feeders were correctly identified by preoperative 4D-MRA (7 additional arterial feeders identified by DSA only: group 1, 3/19; group 2, 4/36). Postoperative 4D-MRA and DSA matched in 25/25 patients (residual filling, 1/25). Vessel sharpness and diameters did not differ substantially between the 2 groups. VBC was significantly higher in group 2 (P < .005). CONCLUSIONS: 4D-MRA is a reliable tool that allows predicting Spetzler-Martin classification and postoperative residual filling; it hence allows substituting DSA in the pre- and postoperative evaluation of patients with cerebral AVMs. PMID- 22300926 TI - Multimodal reperfusion therapy for large hemispheric infarcts in octogenarians: is good outcome a realistic goal? AB - BACKGROUND AND PURPOSE: MMRT may be beneficial in a subset of patients with large hemispheric stroke who cannot be treated with systemic thrombolysis. Because most previous studies only included relatively young patients, the outcome of very old patients given MMRT remains unknown. MATERIALS AND METHODS: Consecutive patients with large hemispheric stroke treated with MMRT and admitted to intensive care were included. We compared neurologic and functional outcomes between patients younger and older than 80 years. RESULTS: We included 14 patients older than 80 years and compared them with 66 patients who were younger than 80. Cerebrovascular risk factor profile, admission NIHSS scores, stroke etiology and pathogenesis, and procedure-related variables did not differ between the groups except for a higher prevalence of smoking in younger patients. Excellent target vessel recanalization (Thrombolysis in Myocardial Infarction score of 3) and good outcome at 90 days (modified Rankin Score <= 2) were more common in younger patients (45% versus 14%, P = .047, and 41% versus 0%, P = .008, respectively). In contrast, mortality rates were higher in octogenarians (43% versus 17%, respectively). CONCLUSIONS: In this study, very old patients had higher chances of mortality and a very low probability of achieving functional independence even after MMRT. Further prospective studies are needed to examine the futility of MMRT in the very old. PMID- 22300927 TI - Diffusion tensor imaging of the normal pediatric spinal cord using an inner field of view echo-planar imaging sequence. AB - BACKGROUND AND PURPOSE: DTI in the brain has been well established, but its application in the spinal cord, especially in pediatrics, poses several challenges. The small cord size has inherent low SNR of the diffusion signal intensity, respiratory and cardiac movements induce artifacts, and EPI sequences used for obtaining diffusion indices cause eddy-current distortions. The purpose of this study was to 1) evaluate the accuracy of cervical spinal cord DTI in children using a newly developed iFOV sequence with spatially selective 2D-RF excitations, and 2) examine reproducibility of the DTI measures. MATERIALS AND METHODS: Twenty-five typically developing subjects were imaged twice using a 3T scanner. Axial DTI images of the cervical spinal cord were acquired with this sequence. After motion correction, DTI indices were calculated using regions of interest manually drawn at every axial section location along the cervical spinal cord for both acquisitions. Various DTI indices were calculated: FA, AD, RD, MD, RA, and VR. Geometric diffusion measures were also calculated: Cp, Cl, and Cs. RESULTS: The following average values for each index were obtained: FA = 0.50 +/- 0.11; AD = 0.97 +/- 0.20 * 10(-3)mm(2)/s; RD = 0.41 +/- 0.13 * 10(-3)mm(2)/s; MD = 0.59 +/- 0.15 * 10(-3)mm(2)/s; RA = 0.35 +/- 0.08; VR = 0.03 +/- 0.00; Cp = 0.13 +/- 0.07; Cl = 0.29 +/- 0.09; and Cs = 0.58 +/- 0.11. The reproducibility tests showed moderate to strong ICC in all subjects for all DTI parameters (ICC>0.72). CONCLUSIONS: This study showed that accurate and reproducible DTI parameters can be estimated in the pediatric cervical spinal cord using an iFOV EPI sequence. PMID- 22300928 TI - Ultrasound-based diagnostic classification for solid and partially cystic thyroid nodules. AB - BACKGROUND AND PURPOSE: The ability of US to differentiate benign thyroid nodules from malignant ones is still a matter of debate. The aim of this study was to assess the diagnostic efficacy of a US-based classification system for solid and PCTNs through a prospectively designed study. MATERIALS AND METHODS: We studied 1289 thyroid nodules in 1036 patients who underwent thyroid US, US-FNA, and thyroid surgery. Each thyroid nodule was prospectively classified into 1 of 5 diagnostic categories following real-time US examination: benign, probably benign, borderline, possibly malignant, and malignant. Solid nodules were classified by using all 5 categories, and PCTNs were classified by all except the borderline category. We calculated the diagnostic efficacy of thyroid US by comparing US diagnoses with histopathologic results of surgically resected thyroid nodules. RESULTS: One thousand fifty-five solid nodules and 234 PCTNs were prospectively classified as benign (n = 435 and 179), probably benign (n = 213 and 25), borderline (n = 94 and 0), possibly malignant (n = 115 and 15), and malignant (n = 198 and 15), respectively. Of these 1289 nodules, 505 were surgically resected and confirmed by pathology (191 benign and 314 malignant nodules); there were 44 resected solid nodules with a borderline category. For solid nodules and PCTNs, the sensitivity, specificity, positive and negative predictive values, and accuracy of US diagnosis were 86.1 and 66.7, 90.0 and 88.9, 94.3 and 75.0, 77.3 and 84.2, and 87.5% and 81.5%, respectively, based on 505 surgical specimens and excluding the 42 solid borderline nodules. CONCLUSIONS: Our US-based classification system can provide helpful guidance for the management of thyroid nodules. PMID- 22300929 TI - Cavernous sinus segment internal carotid artery aneurysms: whether and how to treat. PMID- 22300930 TI - Low kilovoltage CT of the neck with 70 kVp: comparison with a standard protocol. AB - BACKGROUND AND PURPOSE: CT protocols should aim for radiation doses being as low as reasonably achievable. The purpose of our study was to assess the image quality and radiation dose of neck CT at a tube potential of 70 kVp. MATERIALS AND METHODS: Twenty patients (7 female, mean age 51.4 years, age range 19-81 years) underwent contrast-enhanced 64-section CT of the neck at 70 kVp (ATCM, effective tube current-time product 614 eff.mAs, range 467-713 eff.mAs). All 20 patients had a previous neck CT at 120 kVp on the same scanner. Two radiologists assessed image quality and artifacts in the upper, middle, and lower neck. Image noise and attenuation were measured, and the CNR was calculated. Effective radiation dose was calculated. RESULTS: Interobserver agreement regarding image quality of soft tissue for 70-kVp and 120-kVp scans was good to excellent. At 70 kVp, soft tissues were of diagnostic image quality in all scans, whereas the lower cervical spine was not of diagnostic quality in 3 and 4 scans per both readers. No difference was found among 70-kVp and 120-kVp scans for soft tissue image quality in the upper neck, while image quality was significantly better in the middle at 70 kVp (P < .05) and better in the lower third at 120 kVp (P < .05). CNR was significantly higher at 70 kVp in all levels for both readers (P < .001). Effective radiation dose at 70 kVp was significantly lower (0.88 +/- 0.2 mSv) than at 120 kVp (1.33 +/- 0.2 mSv, P < .001). CONCLUSIONS: CT of the cervical soft tissues at 70 kVp is feasible, provides diagnostic image quality with improved CNR, and reduces radiation dose by approximately 34% compared with a standard protocol at 120 kVp. In contrast, low kVp CT of the lower cervical spine suffers from compromised image quality. PMID- 22300931 TI - Explaining clinical effects of deep brain stimulation through simplified target specific modeling of the volume of activated tissue. AB - BACKGROUND AND PURPOSE: Although progress has been made in understanding the optimal anatomic structures as target areas for DBS, little effort has been put into modeling and predicting electromagnetic field properties of activated DBS electrodes and understanding their interactions with the adjacent tissue. Currently, DBS is performed with the patient awake to assess the effectiveness and the side effect spectrum of stimulation. This study was designed to create a robust and rather simple numeric and visual tool that provides sufficient and practical relevant information to visualize the patient's individual VAT. MATERIALS AND METHODS: Multivariate polynomial fitting of previously obtained data from a finite-element model, based on a similar DBS system, was used. The model estimates VAT as a first-approximation sphere around the active DBS contact, using stimulation voltages and individual tissue-electrode impedances. Validation uses data from 2 patients with PD by MR imaging, DTI, fiber tractography, and postoperative CT data. RESULTS: Our model can predict VAT for impedances between 500 and 2000 Omega with stimulation voltages up to 10 V. It is based on assumptions for monopolar DBS. Evaluation of 2 DBS cases showed a convincing correspondence between predicted VAT and neurologic (side) effects (internal capsule activation). CONCLUSIONS: Stimulation effects during DBS can be readily explained with this simple VAT model. Its implementation in daily clinical routine might help in understanding the types of tissues activated during DBS. This technique might have the potential to facilitate DBS implantations with the patient under general anesthesia while yielding acceptable clinical effectiveness. PMID- 22300932 TI - Widespread microstructural white matter involvement in amyotrophic lateral sclerosis: a whole-brain DTI study. AB - BACKGROUND AND PURPOSE: The extensive application of advanced MR imaging techniques to the study of ALS has undoubtedly improved our knowledge of disease pathophysiology, even if the actual spread of the neurodegenerative process throughout the central nervous system is not fully understood. The present study aimed to detect WM patterns of microstructural abnormalities to better investigate the pathologic process in ALS, within but also beyond CSTs, in a whole-brain analysis. MATERIALS AND METHODS: DTI was performed in 19 patients with ALS and 20 matched healthy controls, by using whole-brain TBSS and VOI analyses. RESULTS: We observed a significant decrease of FA in the body of CC of the ALS group (P < .05). At the VOI level, both FA decrease and RD increase in the body of CC significantly correlated with the UMN score (P = .003 and P = .02). Additionally, significant voxelwise positive correlations between FA and the ALSFRS-R were detected in the WM tracts underneath the left premotor cortex (P < .05). CONCLUSIONS: The correlations between reduction of FA and increase of RD in the body of CC with the UMN score indicate that the WM degeneration in the CC is strictly related to the ALS pyramidal impairment, while the correlation between FA and ALSFRS-R in the associative tracts underneath the left premotor cortex might reflect the progressive spread of the disease from the motor toward the extramotor areas. PMID- 22300933 TI - Quality control in neuroradiology: impact of trainees on discrepancy rates. AB - BACKGROUND AND PURPOSE: Prior studies have found a 2%-8% clinically significant error rate in radiology practice. We compared discrepancy rates of studies interpreted by subspecialty-trained neuroradiologists working with and without trainees. MATERIALS AND METHODS: Subspecialty-trained neuroradiologists reviewed 2162 studies during 41 months. Discrepancies between the original and "second opinion" reports were scored: 1, no change; 2, clinically insignificant detection discrepancy; 3, clinically insignificant interpretation discrepancy; 4, clinically significant detection discrepancy; and 5, clinically significant interpretation discrepancy. Faculty alone versus faculty and trainee discrepancy rates were calculated. RESULTS: In 87.6% (1894/2162), there were no discrepancies with the original report. The neuroradiology division had a 1.8% (39/2162; 95% CI, 1.3%-2.5%) rate of clinically significant discrepancies. In cases reviewed solely by faculty neuroradiologists (16.2% = 350/2162 of the total), the rate of discrepancy was 1.7% (6/350). With fellows (1232/2162, 57.0% of total) and residents (580/2162, 26.8% of total), the rates of discrepancy were 1.6% (20/1232) and 2.2% (13/580), respectively. The odds of a discrepant result were 26% greater (OR = 1.26; 95% CI, 0.38-4.20) when reading with a resident and 8% less (OR = 0.92; 95% CI, 0.35-2.44) when reading with a fellow than when reading alone. CONCLUSIONS: There was a 1.8% rate of clinically significant detection or interpretation discrepancy among academic neuroradiologists. The difference in the discrepancy rates between faculty only (1.7%), fellows and faculty (1.6%), and residents and faculty (2.2%) was not statistically significant but showed a trend indicating that reading with a resident increased the odds of a discrepant result. PMID- 22300934 TI - Zuckerkandl tubercle of the thyroid: a common imaging finding that may mimic pathology. AB - BACKGROUND AND PURPOSE: The posterior thyroid tubercle, also known as ZT, is an important surgical landmark due to its close proximity to the recurrent laryngeal nerve. A recent case of ZT with a nodular configuration caused clinical concern but was shown on biopsy to be normal thyroid tissue. The purpose of this study was to review a series of CT neck studies to identify how often ZT-specifically, a nodular subtype-was present. MATERIALS AND METHODS: A total of 96 neck CTs from sequential patients were retrospectively identified from January 2010 to July 2010. ZT was defined on imaging as a thyroid lobe extending posterior to the tracheoesophageal groove. A nodular subtype was defined as having a narrowed neck at the level of the tracheoesophageal groove. RESULTS: There were 31 women and 45 men (mean age of 56.1 years, range 22-100 years) who met inclusion criteria. Sixty-seven patients had thyroid glands that extended posterior to the tracheoesophageal groove at CT imaging; this finding was bilateral in 43 patients, more commonly on the right (60 versus 49). Thirty-two of these patients (42.1%; 16 male, 16 female) had a nodular subtype. CONCLUSIONS: ZT is an important surgical landmark of the thyroid that has important radiologic variations. It has a nodular shape in over a third of CT neck studies in our series. Recognition of this feature of the thyroid gland at CT imaging can obviate the need for biopsy and avoid potential recurrent laryngeal nerve injury. PMID- 22300935 TI - Automatic voxel-based morphometry of structural MRI by SPM8 plus diffeomorphic anatomic registration through exponentiated lie algebra improves the diagnosis of probable Alzheimer Disease. AB - BACKGROUND AND PURPOSE: The necessity for structural MRI is greater than ever to both diagnose AD in its early stage and objectively evaluate its progression. We propose a new VBM-based software program for automatic detection of early specific atrophy in AD. MATERIALS AND METHODS: A target VOI was determined by group comparison of 30 patients with very mild AD and 40 age-matched healthy controls by using SPM. Then this target VOI was incorporated into a newly developed automated software program independently running on a Windows PC for VBM by using SPM8 plus DARTEL. ROC analysis was performed for discrimination of 116 other patients with AD with very mild stage (n = 45), mild stage (n = 30) and moderate-to-advanced stages (n = 41) from 40 other age-matched healthy controls by using a z score map in the target VOI. RESULTS: Medial temporal structures involving the entire region of the entorhinal cortex, hippocampus, and amygdala showed significant atrophy in the patients with very mild AD and were determined as a target VOI. When we used the severity score of atrophy in this target VOI, 91.6%, 95.8%, and 98.2% accuracies were obtained in the very mild AD, mild AD, and moderate-to-severe AD groups, respectively. In the very mild AD group, a high specificity of 97.5% with a sensitivity of 86.4% was obtained, and age at onset of AD did not influence this accuracy. CONCLUSIONS: This software program with application of SPM8 plus DARTEL to VBM provides a high performance for AD diagnosis by using MRI. PMID- 22300936 TI - Acute bilateral deafness as the first symptom of Wernicke encephalopathy. PMID- 22300937 TI - Altered fetal cerebral and cerebellar development in twin-twin transfusion syndrome. AB - BACKGROUND AND PURPOSE: Neurodevelopmental disability is common in twins with TTTS in utero; however, the responsible neuropathology remains uncertain. We proposed to document the frequency of brain abnormalities on clinical fetal MR images and to determine if quantitative fetal brain biometric analysis in twin fetuses with TTTS was different from those in healthy control fetuses. MATERIALS AND METHODS: We reviewed the fetal brain MR images of 33 twin pairs with TTTS clinically evaluated in our institution. Eighteen fetal MR images of "healthy" twins with TTTS were further studied with biometric analysis in comparison with GA-matched singleton fetuses to detect quantitative differences in brain growth and development. RESULTS: A higher incidence of anomalies (11/33, 33.3%) was found than previously reported. The most frequent abnormality was ventriculomegaly (7/11, 63%) in both donor and recipient. In "healthy" twins with TTTS, biometric analysis revealed persistently small measurements (cBTD, CMT, TCD, and VAPD) in the donor cerebrum and cerebellum in comparison with their recipient cotwin and healthy control fetuses. These differences were preserved when normalized by cBTD. CONCLUSIONS: Our findings show that significant brain abnormalities are common in TTTS. In addition, diffuse subtle abnormalities are also present in normal-appearing donor fetal brains that cannot be solely explained by overall growth restriction. Such subtle fetal brain anomalies may explain the high incidence of poor long-term neurodevelopmental outcomes of survivors, and they need to be further investigated with more sophisticated quantitative fetal imaging methodologies. PMID- 22300938 TI - A comparison of 2 stroke devices: the new Aperio clot-removal device and the solitaire AB/FR. AB - BACKGROUND AND PURPOSE: Several studies have shown promising results for the use of self-expandable intracranial stents for the treatment of acute ischemic stroke. This new technique combines immediate flow restoration after stent deployment with high recanalization rates. In the present study, the safety and efficacy of the new Aperio clot-removal device was tested in comparison with the Solitaire AB device. MATERIALS AND METHODS: The experiments were performed in swine with a weight of 35-50 kg following established models. The experimental thrombi were prepared by using a new flow model (Thrombus Loop) to produce radiopaque thrombi. Thrombi were cut into lengths of 10 mm and injected into the target vessel. The occlusion was verified by DSA and rated with the help of the TICI score. A microcatheter was placed distal to the thrombus. The devices were placed with the proximal third within the thrombus and were retrieved under continuous aspiration in their released state into the guiding sheath. We performed 23 procedures with the Aperio device and 18 procedures with the Solitaire AB and FR devices. Control angiograms were obtained 3 and 5 minutes after device deployment to evaluate the flow restoration. The number of attempts to reach a TICI 2/3 score was recorded as well as the time to recanalization and the device-related complications. Vasospasm, vascular perforation, intramural arterial dissection, or embolization of a previously uninvolved territory was defined as a device-related complication. RESULTS: Defined radiopaque thrombi from whole blood could reliably be created by using the Thrombus Loop. Both devices demonstrated a high recanalization rate of 100% (TICI 3) in the target vessel with no device-related complications. No significant differences were found between the 2 devices. CONCLUSIONS: In this small study, we could show that radiopaque thrombi of whole blood with a defined diameter could be reliably created by using the Thrombus Loop. The new "stent-retriever" (Aperio System) seems to be a very efficient and safe addition to the existing repertoire of clot removal devices. PMID- 22300939 TI - Effects of perianeurysmal environment during the growth of cerebral aneurysms: a case study. AB - BACKGROUND AND PURPOSE: The natural history of cerebral aneurysms is thought to be governed by multifactorial processes involving hemodynamics, biomechanics, mechanobiology, and perianeurysmal environment. The purpose of this study was to highlight the importance of considering the influence of contacts with perianeurysmal environment structures on the hemodynamics and geometric evolution of intracranial aneurysms. MATERIALS AND METHODS: A large aneurysm of the basilar artery in contact with bone and observed to grow during a 4-year follow-up period was selected for study. Anatomic models were constructed from longitudinal CTA images acquired at 1-year intervals during the observation period. Computational fluid dynamics simulations were carried out under pulsatile flow conditions to analyze the blood flow pattern and WSS distribution in the aneurysm during its evolution. RESULTS: The aneurysm was observed to grow against the bone, resulting in a geometric change of the proximal parent artery, which, in turn, induced substantial changes in the aneurysm hemodynamics. In particular, a region of elevated WSS created by the inflow streams was observed to shift locations around the place where the aneurysm enlarged in contact with the bone as the aneurysm progressed. In addition, a "notch" near the distal end of the aneurysm, away from the bone and subject to relatively high WSS, was observed to grow and, later, completely disappear. CONCLUSIONS: Contacts with perianeurysmal structures need to be considered and analyzed to assess whether they could exert a significant influence on the geometric evolution of each individual intracranial aneurysm and its hemodynamics. PMID- 22300940 TI - Further refining the analysis of interpretation errors in CT angiography of the head and neck. PMID- 22300942 TI - [On the use of SQUIRE]. PMID- 22300941 TI - Deregulation of apoptosis-related genes is associated with PRV1 overexpression and JAK2 V617F allele burden in Essential Thrombocythemia and Myelofibrosis. AB - BACKGROUND: Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) are Chronic Myeloproliferative Neoplasms (MPN) characterized by clonal myeloproliferation/myeloaccumulation without cell maturation impairment. The JAK2 V617F mutation and PRV1 gene overexpression may contribute to MPN physiopathology. We hypothesized that deregulation of the apoptotic machinery may also play a role in the pathogenesis of ET and PMF. In this study we evaluated the apoptosis-related gene and protein expression of BCL2 family members in bone marrow CD34+ hematopoietic stem cells (HSC) and peripheral blood leukocytes from ET and PMF patients. We also tested whether the gene expression results were correlated with JAK2 V617F allele burden percentage, PRV1 overexpression, and clinical and laboratory parameters. RESULTS: By real time PCR assay, we observed that A1, MCL1, BIK and BID, as well as A1, BCLW and BAK gene expression were increased in ET and PMF CD34+ cells respectively, while pro-apoptotic BAX and anti-apoptotic BCL2 mRNA levels were found to be lower in ET and PMF CD34+ cells respectively, in relation to controls. In patients' leukocytes, we detected an upregulation of anti-apoptotic genes A1, BCL2, BCL-XL and BCLW. In contrast, pro apoptotic BID and BIMEL expression were downregulated in ET leukocytes. Increased BCL-XL protein expression in PMF leukocytes and decreased BID protein expression in ET leukocytes were observed by Western Blot. In ET leukocytes, we found a correlation between JAK2 V617F allele burden and BAX, BIK and BAD gene expression and between A1, BAX and BIK and PRV1 gene expression. A negative correlation between PRV1 gene expression and platelet count was observed, as well as a positive correlation between PRV1 gene expression and splenomegaly. CONCLUSIONS: Our results suggest the participation of intrinsic apoptosis pathway in the MPN physiopathology. In addition, PRV1 and JAK2 V617F allele burden were linked to deregulation of the apoptotic machinery. PMID- 22300943 TI - Conserved regulators of the cell separation process in Schizosaccharomyces. AB - The fission yeasts (Schizosaccharomyces) representing a highly divergent phylogenetic branch of Fungi evolved from filamentous ancestors by gradual transition from mycelial growth to yeast morphology. For the transition, a mechanism had been developed that separates the sister cells after the completion of cytokinesis. Numerous components of the separation mechanism have been characterised in Schizosaccharomycespombe, including the zinc-finger transcription factor Ace2p and the fork-head transcription factor Sep1p. Here we show that both regulators have regions conserved within the genus. The most conserved parts contain the DNA-binding domains whose amino-acid sequences perfectly reflect the phylogenetic positions of the species. The less conserved parts of the proteins contain sequence blocks specific for the whole genus or only for the species propagating predominantly or exclusively as yeasts. Inactivation of either gene in the dimorphic species Schizosaccharomycesjaponicus abolished cell separation in the yeast phase conferring hypha-like morphology but did not change the growth pattern to unipolar and did not cause extensive polar vacuolation characteristic of the true mycelium. Neither mutation affected the mycelial phase, but both mutations hampered the hyphal fragmentation at the mycelium-to-yeast transition. Ace2p(Sj) acts downstream of Sep1p(Sj) and regulates the orthologues of the Ace2p-dependent S.pombe genes agn1(+) (1,3-alpha glucanase) and eng1(+) (1,3-beta-glucanase) but does not regulate the orthologue of cfh4(+) (chitin synthase regulatory factor). These results and the complementation of the cell separation defects of the ace2(-) and sep1(-) mutations of S.pombe by heterologously expressed ace2(Sj) and sep1(Sj) indicate that the cell separation mechanism is conserved in the Schizosaccharomyces genus. PMID- 22300944 TI - The GATA factors AREA and AREB together with the co-repressor NMRA, negatively regulate arginine catabolism in Aspergillus nidulans in response to nitrogen and carbon source. AB - The filamentous fungus Aspergillus nidulans can utilize arginine both as a nitrogen and carbon source. Analysis of areA and areB single and double mutants has shown that the two GATA transcription factors AREA and AREB negatively regulate the expression of arginine catabolism genes agaA and otaA under nitrogen repressing conditions. AREA is necessary for the ammonium repression of agaA and otaA under carbon repressing conditions, while AREB is involved under carbon limiting conditions. The ability of both AREA and AREB to sense the status of carbon metabolism is most probably dependent on NMRA, and not on the transcription factor CREA, which mediates general carbon catabolite repression in A. nidulans. NMRA is a co-repressor which has previously been shown to bind the C terminus of AREA and inhibits its activity under conditions of nitrogen sufficiency, in response to high intracellular glutamine levels. We therefore propose a novel function for NMRA, the modulation of AREA and AREB activity in response to the carbon status of the cell. PMID- 22300945 TI - Radioluminescence of red-emitting Eu-doped phosphors for fiberoptic dosimetry. AB - Fiberoptic dosimetry (FOD) technique has become an attractive method for real time dosimetry. Al(2)O(3):Cis one of the most used radioluminescence materials for FOD due to its high efficiency but it presents the drawback of emitting in the spectral region, where spurious luminescence is also important. Optical filtering is the simplest technique to remove spurious luminescence, but is useful when red-emitting scintillators are employed. In this work, the feasibility of using red-emitting Eu-doped phosphors as FOD scintillators has been investigated. PMID- 22300946 TI - Evidence for a shift to anaerobic metabolism in adipose tissue in efavirenz containing regimens for HIV with different nucleoside backbones. AB - BACKGROUND: Antiretroviral (ARV) treatment has been associated with abnormalities in lipid and mitochondrial metabolism. We compared patterns of gene expression in the subcutaneous adipose tissue (SAT) of HIV-positive subjects before and after 18-24 months of ARV therapy with HIV-negative controls. METHODS: HIV patients naive to ARV were randomized to receive zidovudine (AZT), lamivudine (3TC) with efavirenz (EFV) or tenofovir disoproxil fumarate (TDF) with emtricitabine (FTC) and EFV. Healthy controls (n=15) were matched for age, ethnicity and gender. Patients on a regimen containing abacavir (ABC), 3TC and EFV for 18-24 months were also tested. Genes involved in adipocyte glucocorticoid, lipid and mitochondrial metabolism, and adipocyte differentiation, were profiled with real time PCR. RESULTS: AZT led to increased visceral adipose tissue (VAT; P=0.012) and VAT:SAT ratio (P=0.036), whereas TDF increased SAT (P=0.047) and peripheral fat/lean body mass ratio (P=0.017). HIV treatment-naive patients had lower plasma lipoprotein lipase (LPL) activity (P=0.0001) versus controls (remaining below controls after ARV; P=0.038-0.0001). The overall pattern of gene expression was similar across all treatment groups, being most marked with AZT and least with TDF. There was up-regulation of peroxisome proliferator-activated receptor-gamma coactivator-1alpha, uncoupling protein-2 and hexose 6-phosphate dehydrogenase, and down-regulation of nuclear respiratory factor-1, cytochrome oxidase B, cytochrome c oxidase-4, uncoupling protein-3, 11beta-hydroxysteroid dehydrogenase type-1, glucocorticoid receptor-alpha, fatty acid synthase, fatty acid binding protein-4, LPL and hormone sensitive lipase (18-24 months post-treatment versus pretreatment levels and controls; P<0.05 to <0.0001). CONCLUSIONS: The decreased expression of genes involved in lipid and mitochondrial metabolism 18-24 months post-ARV treatment in SAT of HIV patients, in conjunction with the increase in uncoupling protein-2 and decrease in cytochrome oxidase B gene expression, provides evidence of mitochondrial dysfunction and a shift to anaerobic metabolism within SAT in EFV-containing ARV regimens. PMID- 22300947 TI - Recurrent self-limited hyperthermia following ECT for catatonia in a young man with cerebral palsy. PMID- 22300948 TI - Involvement of G protein and purines in Rhinella arenarum oocyte maturation. AB - We investigated the participation of G(alphai) protein and of intracellular cAMP levels on spontaneous and progesterone-mediated maturation in Rhinella arenarum fully grown follicles and denuded oocytes. Although progesterone is the established maturation inducer in amphibians, Rhinella arenarum oocytes obtained during the reproductive period (competent oocytes) resume meiosis with no need for an exogenous hormonal stimulus if deprived of their enveloping follicular cells, a phenomenon called spontaneous maturation. In amphibian oocytes, numerous signalling mechanisms have been involved in the rapid, non-genomic, membrane effects of progesterone, but most of these are not fully understood. The data presented here demonstrate that activation of the G(alphai) protein by Mas-7 induced maturation in non-competent oocytes and also an increase in GVBD (germinal vesicle breakdown) in competent oocytes. Similar results were obtained with intact follicles independent of the season. The activation of adenylyl cyclase (AC) by forskolin seems to inhibit both spontaneous and progesterone induced GVBD. In addition, the high intracellular levels of cAMP caused by activation of AC by forskolin treatment or addition of db-cAMP inhibited maturation that had been induced by Mas-7 and in a dose-dependent manner. Treatment with H-89, a protein kinase A (PKA) inhibitor, was able to trigger GVBD in a dose-dependent manner in non-competent oocytes and increased the percentages of GVBD in oocytes competent to mature spontaneously. The results obtained with whole follicles and denuded oocytes were similar, which suggested that effects on AC and PKA were not mediated by follicle cells. The fact that Mas-7 was able to induce maturation in non-competent oocytes in a similar manner to progesterone and to increase spontaneous maturation suggests that G(alphai) activation could be an important step in meiosis resumption. Thus, the decrease in cAMP as a result of the regulation of the G proteins on AC and the inactivation of PKA by H 89 could contribute to the activation of MPF (maturation promoting factor) and induce maturation of the oocytes of Rhinella arenarum. PMID- 22300949 TI - Clinicopathological significance of non-small cell lung cancer with high prevalence of Oct-4 tumor cells. AB - BACKGROUND: Expression of the stem cell marker octamer 4 (Oct-4) in various neoplasms has been previously reported, but very little is currently known about the potential function of Oct-4 in this setting. The purpose of this study was to assess the prognostic value of Oct-4 expression after surgery in primary non small cell lung cancer (NSCLC) and investigate its possible molecular mechanism. METHODS: We measured Oct-4 expression in 113 NSCLC tissue samples and three cell lines by immunohistochemical staining and RT-PCR. The association of Oct-4 expression with demographic characteristics, proliferative marker Ki67, microvessel density (MVD), and expression of vascular endothelial growth factor (VEGF) were assessed. RESULTS: Oct-4 expression was detected in 90.3% of samples and was positively correlated with poor differentiation and adenocarcinoma histology, and Oct-4 mRNA was found in each cell lines detected. Overexpression of Oct-4 had a strong association with cells proliferation in all cases, MVD negative, and VEGF-negative subsets. A Kaplan-Meier analysis showed that overexpression of Oct-4 was associated with shorter overall survival in all cases, adenocarcinoma, squamous cell carcinoma, MVD-negative, and VEGF-negative subsets. A multivariate analysis demonstrated that Oct-4 level in tumor tissue was an independent prognostic factor for overall survival in all cases, MVD negative, and VEGF-negative subsets. CONCLUSION: Our findings suggest that, even in the context of vulnerable MVD status and VEGF expression, overexpression of Oct-4 in tumor tissue represents a prognostic factor in primary NSCLC patients. Oct-4 may maintain NSCLC cells in a poorly differentiated state through a mechanism that depends on promoting cell proliferation. PMID- 22300950 TI - Alzheimer's disease and age-related macular degeneration have different genetic models for complement gene variation. AB - Alzheimer's disease (AD) and age-related macular degeneration (AMD) are both neurodegenerative disorders which share common pathological and biochemical features of the complement pathway. The aim of this study was to investigate whether there is an association between well replicated AMD genetic risk factors and AD. A large cohort of AD (n = 3898) patients and controls were genotyped for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), the Age related maculopathy susceptibility protein 2 (ARMS2) the complement component 2 (C2), the complement factor B (CFB), and the complement component 3 (C3) genes. While significant but modest associations were identified between the complement factor H, the age-related maculopathy susceptibility protein 2, and the complement component 3 single nucleotide polymorphisms and AD, these were different in direction or genetic model to that observed in AMD. In addition the multilocus genetic model that predicts around a half of the sibling risk for AMD does not predict risk for AD. Our study provides further support to the hypothesis that while activation of the alternative complement pathway is central to AMD pathogenesis, it is less involved in AD. PMID- 22300952 TI - Acute moderate exercise enhances compensatory brain activation in older adults. AB - A growing number of reports state that regular exercise enhances brain function in older adults. Recently a functional near-infrared spectroscopy (fNIRS) study revealed that an acute bout of moderate exercise enhanced activation of the left dorsolateral prefrontal cortex (L-DLPFC) associated with Stroop interference in young adults. Whether this acute effect is also applicable to older adults was examined. Sixteen older adults performed a color-word matching Stroop task before and after 10 minutes of exercise on a cycle ergometer at a moderate intensity. Cortical hemodynamics of the prefrontal area was monitored with a fNIRS during the Stroop task. We analyzed Stroop interference (incongruent-neutral) as Stroop performance. Though activation for Stroop interference was found in the bilateral prefrontal area before the acute bout of exercise, activation of the right frontopolar area (R-FPA) was enhanced after exercise. In the majority of participants, this coincided with improved performance reflected in Stroop interference results. Thus, an acute bout of moderate exercise improved Stroop performance in older adults, and this was associated with contralateral compensatory activation. PMID- 22300951 TI - Expression pattern of oxidative stress and antioxidant defense-related genes in the aging Fischer 344/NHsd rat cochlea. AB - The biological mechanisms that give rise to age-related hearing loss (ARHL) are still poorly understood. However, there is growing recognition that oxidative stress may be an important factor. To address this issue, we measured the changes in the expression of cochlear oxidative stress and antioxidant defense-related genes in young (2 months old), middle-aged (12 months old), and old (21-25 months old) Fischer 344/NHsd (F344/NHsd) rats and compared gene expression changes with ARHL. A quantitative real-time reverse transcription polymerase chain reaction array revealed a significant age-related downregulation of only 1 gene, stearoyl coenzyme A desaturase 1, and upregulation of 12 genes: 24-dehydrocholesterol reductase; aminoadipate-semialdehyde synthase; cytoglobin; dual oxidase 2; glutathione peroxidase 3; glutathione peroxidase 6; glutathione S-transferase, kappa 1; glutathione reductase; nicotinamide adenine dinucleotide phosphate (NAD(P)H) dehydrogenase, quinone 1; solute carrier Family 38, Member 5; thioredoxin interacting protein; and vimentin. Statistical analyses revealed significant correlations between gene expression and auditory function in 8 genes. Our results identified specific subsets of oxidative stress genes that appear to play an important role in ARHL in the Fischer 344/NHsd rat. PMID- 22300953 TI - Role of age and tumour stage in the temporal pattern of 'cure' from stomach cancer: a population-based study in Osaka, Japan. AB - OBJECTIVES: To evaluate progress in stomach cancer care in Japan since 1975. DESIGN: Population-based study of data extracted from the Osaka Cancer Registry. SETTING: Population-based cancer registry in the area of Osaka Prefecture. PARTICIPANTS: All 66,032 cases diagnosed with a stomach cancer in Osaka Prefecture, Japan between 1975 and 2000 and registered in the Osaka Cancer Registry. MAIN OUTCOME MEASURES: 'Cure' fraction and median survival time for 'uncured' patients were estimated with multivariable mixture 'cure' model. The role played by age and stage at diagnosis on the changes in 'cure' parameters between 1975 and 2000 was evaluated. Missing stage was handled by multiple imputation approach. RESULTS: More than 50% of the patients diagnosed with a stomach cancer in 1996-2000 were estimated 'cured' from their cancer, corresponding to a 20% increase since 1975-1980. Median survival time for 'uncured' patients however remained unchanged at about 8 months. 'Cure' fraction was over 85% for localised tumours and 30% for regional tumours, but stayed as low as 2.5% for distant metastatic cancers. Improvement was underestimated by about 10% because of ageing of cancer patients. Changes in stage distribution explained up to 40% of the increase in 'cure' fraction among men and up to 13% in women. Overdiagnosis was unlikely to play any role in these patterns. CONCLUSIONS: 'Cure' fraction from stomach cancer dramatically increased in Osaka, Japan since 1975, partly because of earlier stage at diagnosis, but mostly due to improvement in treatment of stomach cancer patients. This study, based on a leading country in term of stomach cancer management, provides insightful results for other countries in which 'cure' fraction is usually much lower. PMID- 22300954 TI - The presence of genes encoding for different virulence factors in clonally related Escherichia coli that produce CTX-Ms. AB - Successful international clones have recently emerged among Escherichia coli that produce CTX-M beta-lactamases as important causes of community-onset urinary tract and bloodstream infections. One hundred and seven isolates that belong to sequence types (STs) ST38, ST131, ST405, ST648, and 38 nonrelated CTX-M-producing E. coli from Canada and the Netherlands were assigned to phylogenetic groups and tested for the presence of genes encoding for virulence factors (VFs) using established multiplex polymerase chain reaction. The STs E. coli were significantly more resistant to antibiotics--ST38, ST405, and ST648 belonged to phylogenetic group D while ST131 belonged to B2. Secreted autotransporter toxin (sat), aerobactin receptor, and pathogenicity island marker were significantly more common among the STs; the heat-resistant agglutinin (hra) was present in ST38, sat, and uropathogenic-specific protein, and putative adhesin-siderophore receptor was more common in ST131, while outer membrane protease T was present in ST648. ST131 had a significantly higher VF score. In conclusion, the precise role of these VFs remains to be elucidated; however, we have identified certain putative VFs that possibly contribute to the fitness and success of certain sequence types. PMID- 22300955 TI - Fecal colonization of VIM-1-producing Klebsiella pneumoniae and in vivo transfer of multidrug-resistant IncN plasmid in a renal transplant patient. AB - We report a case of long-term colonization of a carbapenemase (VIM)-producing Klebsiella pneumoniae clone in a renal transplant patient and demonstrate the in vivo transmission of a broad-host-range multidrug-resistant IncN plasmid containing bla(VIM), bla(SHV-12), and qnrS to Escherichia coli. PMID- 22300956 TI - Evaluation of the PrimerDesignTM genesig real-time reverse transcription polymerase chain reaction assay and the INFINITI(r) Respiratory Viral Panel Plus assay for the detection of human metapneumovirus in Kuwait. AB - Human metapneumovirus (hMPV) is a respiratory pathogen that was discovered in 2001 and is considered a major cause of both upper and lower respiratory tract infections. A sensitive, fast, and high-throughput diagnostic test is needed for the detection of hMPV that may assist in the clinical management as well as in the reduction of inappropriate therapy. Therefore, a comparison assessment was performed in this study between the PrimerDesignTM genesig real-time reverse transcription-polymerase chain reaction (RT-PCR) Assay and the INFINITI((r)) Respiratory Viral Panel Plus Assay (RVP-Plus) for the detection of hMPV infection in patients with respiratory tract infections. A total of 200 respiratory samples were collected from 185 hospitalized patients, during the winter season in Kuwait. Of 185 patients, 10 (5.4%) were positive for hMPV RNA by the in-house RT PCR assay, while 7 (4%) were positive for hMPV RNA by the real-time RT-PCR assay and 9 (5%) were positive for hMPV RNA by the INFINITI((r)) RVP-Plus assay. The high incidence rate (60%) of hMPV infection was in January 2011. The sensitivity of the real-time RT-PCR and INFINITI((r)) RVP-Plus assays was 70% and 90%, respectively, with specificity of 100% for both assays. hMPV types A and B could be identified in this study; however, discordant genotyping results were found between the direct sequencing method and the INFINITI((r)) RVP-Plus assay in 33% of hMPV-positive patients. PMID- 22300957 TI - Ultrasonographic evaluation of knee joints in patients with Lyme disease. AB - OBJECTIVE: The aim of this study was to evaluate the ultrasonographic images of patients with chronic knee pain and serologic features of Lyme disease. METHODS: Seventy-six patients hospitalized in The Department of Infectious Diseases and Neuroinfections of the Medical University in Bialystok, Poland were included in the study. Patients were divided into two groups: (1) the Lyme disease group included patients with pain in one or both knees and anti-Borrelia burgdorferi antibodies with symptoms lasting for over 6 months; (2) the control group included patients suffering from pain in one or both knees for over 6 months, but for whom B. burgdorferi infection was excluded. RESULTS: The most frequent ultrasonographic finding in the Lyme disease group was effusion, and its frequency was significantly higher than in the control group. No patient in the control group presented with synovitis or cartilage damage, while these were quite frequent findings in the Lyme disease group. Baker's cysts were more frequent in the Lyme disease group, but this was statistically non-significant. CONCLUSIONS: Ultrasonography may be useful in following the sequelae of Lyme disease. The abnormalities found in Lyme disease patients are non-specific and ultrasonography is not useful in the differential diagnosis. PMID- 22300958 TI - The expanding appreciation of heparanase in human disease. PMID- 22300959 TI - Radiation dosimetry of the translocator protein ligands [18F]PBR111 and [18F]PBR102. AB - INTRODUCTION: The translocator protein (TSPO) ligands [18F]PBR111 and [18F]PBR102 show promise for imaging neuroinflammation. Our aim was to estimate the radiation dose to humans from primate positron emission tomography (PET) studies using these ligands and compare the results with those obtained from studies in rodents. METHODS: [18F]PBR111 and [18F]PBR102 PET-computed tomography studies were carried out in baboons. The cumulated activity in the selected source organs was obtained from the volume of interest time-activity curves drawn on coronal PET slices and adjusted for organ mass relative to humans. Radiation dose estimates were calculated in OLINDA/EXM Version 1.1 from baboon studies and compared with those calculated from Sprague-Dawley rat tissue concentration studies, also adjusted for relative organ mass. RESULTS: In baboons, both ligands cleared rapidly from brain, lung, kidney and spleen and more slowly from liver and heart. For [18F]PBR111, the renal excretion fraction was 6.5% and 17% for hepatobiliary excretion; for [18F]PBR102, the renal excretion was 3.0% and 15% for hepatobiliary excretion. The estimated effective dose in humans from baboon data was 0.021 mSv/MBq for each ligand, whilst from rat data, the estimates were 0.029 for [18F]PBR111 and 0.041 mSv/MBq for [18F]PBR102. CONCLUSION: Biodistribution in a nonhuman primate model is better suited than the rat model for the calculation of dosimetry parameters when translating these ligands from preclinical to human clinical studies. Effective dose calculated from rat data was overestimated compared to nonhuman primate data. The effective dose coefficient for both these TSPO ligands determined from PET studies in baboons is similar to that for [18F]FDG. PMID- 22300960 TI - A fast chemoenzymatic synthesis of [11C]-N5,N10-methylenetetrahydrofolate as a potential PET tracer for proliferating cells. AB - INTRODUCTION: Thymidylate synthase and folate receptors are well-developed targets of cancer therapy. Discovery of a simple and fast method for the conversion of 11CH3Ito[11C]-formaldehyde (11CH2O) encouraged us to label the co factor of this enzyme. Preliminary studies conducted on cell lines have demonstrated a preferential uptake of [11-14C]-(R)-N5,N10-methylene-5,6,7,8 tetrahydrofolate (14CH2H4folate) by cancerous cell vs. normal cells from the same organ (Saeed M., Sheff D. and Kohen A. Novel positron emission tomography tracer distinguishes normal from cancerous cells. J Biol Chem 2011;286:33872-33878), pointing out 11CH2H4folate as a positron emission tomography (PET) tracer for cancer imaging. Herein we report the synthesis of 11CH2H4folate, which may serve as a potential PET tracer. METHODS: In a remotely controlled module, methyl iodide (11CH3I) was bubbled into a reaction vial containing trimethylamine N oxide in N,N-Dimethylformamide (DMF) and heated to 70 degrees C for 2 min. Formaldehyde (11CH2O) formed after the completion of reaction was then mixed with a solution of freshly prepared tetrahydrofolate (H4folate) by using a fast chemoenzymatic approach to accomplish synthesis of 11CH2H4folate. Purification of the product was carried out by loading the crude reaction mixture on a SAX cartridge, washing with water to remove unbound impurities and finally eluting with a saline solution. RESULTS: The synthesis and purification of 11CH2H4folate were completed within 5 min. High-performance liquid chromatography analysis of the product after SAX purification indicates that more than 90% of the radioactivity that was retained on the SAX cartridge was in 11CH2H4folate, with minor (<10%) radioactivity due to unreacted 11CH2O. CONCLUSION: We present a fast (~5 min) synthesis and purification of 11CH2H4folate as a potential PET tracer. The final product is received in physiologically compatible buffer (100 mM sodium phosphate, pH 7.0 containing 500 mM NaCl) and ready for use in vivo. PMID- 22300961 TI - The vitamin D receptor gene bAt (CCA) haplotype impairs the response to pegylated interferon/ribavirin-based therapy in chronic hepatitis C patients. AB - BACKGROUND: Chronic hepatitis C infection is a major cause of end-stage liver disease. Therapy outcome is influenced by 25-OH vitamin D deficiency. To further address this observation, our study investigates the impact of the vitamin D receptor (NR1I1) haplotype and combined effects of plasma vitamin D levels in a well-described cohort of hepatitis C patients. METHODS: A total of 155 chronic hepatitis C patients were recruited from the Swiss Hepatitis C Cohort Study for NR1I1 genotyping and plasma 25-OH vitamin D level measurement. NR1I1 genotype data and combined effects of plasma 25-OH vitamin D level were analysed regarding therapy response (sustained virological response). RESULTS: A strong association was observed between therapy non-response and the NR1I1 CCA (bAt) haplotype consisting of rs1544410 (BsmI) C, rs7975232 (ApaI) C and rs731236 (TaqI) A alleles. Of the HCV patients carrying the CCA haplotype, 50.3% were non responders (odds ratio [OR] 1.69, 95% CI 1.07, 2.67; P=0.028). A similar association was observed for the combinational CCCCAA genotype (OR 2.94, 95% CI 1.36, 6.37; P=0.007). The combinational CCCCAA genotype was confirmed as an independent risk factor for non-response in multivariate analysis (OR 2.50, 95% CI 1.07, 5.87; P=0.034). Analysing combined effects, a significant impact of low 25-OH vitamin D levels on sustained virological response were only seen in patients with the unfavourable NR1I1 CCA (bAt) haplotype (OR for non-SVR 3.55; 95% CI 1.005, 12.57; P=0.049). CONCLUSIONS: NR1I1 vitamin D receptor polymorphisms influence response to pegylated-interferon/ribavirin-based therapy in chronic hepatitis C and exert an additive genetic predisposition to previously described low 25-OH vitamin D serum levels. PMID- 22300962 TI - Diffusion tensor imaging localization of the pyramidal tract and spectroscopy in diencephalic pilocytic astrocytoma: a case report. PMID- 22300963 TI - A new in vivo model for luteolysis using systemic pulsatile infusions of PGF(2alpha). AB - A new in vivo model for studying luteolysis was developed in sheep to provide a convenient method for collecting corpora lutea for molecular, biochemical, and histological analysis during a procedure that mimics natural luteolysis. It was found that the infusion of prostaglandin F(2alpha) (PGF(2alpha)) at 20 MUg/min/h into the systemic circulation during the mid luteal phase of the cycle allowed sufficient PGF(2alpha) to escape across the lungs and thus mimic the transient 40% decline in the concentration of progesterone in peripheral plasma seen at the onset of natural luteolysis in sheep. Additional 1h-long systemic infusions of PGF(2alpha), given at physiological intervals, indicated that two infusions were not sufficient to induce luteolysis. However, an early onset of luteolysis and estrus was induced in one out of three sheep with three infusions, two out of three sheep with four infusions, and three out of three sheep with five infusions. Reducing the duration of each systemic infusion of PGF(2alpha) from 1h to 30 min failed to induce luteolysis and estrus even after six systemic infusions indicating that, not only are the amplitude and frequency of PGF(2alpha) pulses essential for luteolysis, but the actual duration of each pulse is also critical. We conclude that a minimum of five systemic pulses of PGF(2alpha), given in an appropriate amount and at a physiological frequency and duration, are required to mimic luteolysis consistently in all sheep. The five pulse regimen thus provides a new accurate in vivo model for studying molecular mechanisms of luteolysis. PMID- 22300964 TI - Non-participation in screening: the case of cervical cancer in Denmark. AB - OBJECTIVE: To determine the impact of comprehensiveness of cytology registration on the proportion of cervical cancer patients without a recent screening history. METHODS: For Danish women diagnosed with cervical cancer in 2003-2007, we used cytology data from the nationwide Danish Pathology Data Bank and the National Health Service Register. In five steps, we included data from an increasing number of cervical screening laboratories into the analysis, and calculated the proportions of screened women who had cytology registered in two screening rounds prior to the cancer diagnosis. RESULTS: In total, 1867 cervical cancer patients were included in the analysis. When looking only at the screening history in the laboratory that diagnosed the cancer, it appeared that only 40% of women were screened in the last two rounds. This proportion increased to 55% when nationwide screening data were used. This corresponded to a 25% decrease in the proportion of patients without a recent screening history. CONCLUSION: The level of comprehensiveness of screening data makes a measurable difference when evaluating the screening histories of women with cervical cancer. It is important that actions for the improvement of a screening program are based on comprehensive cytology registrations. PMID- 22300965 TI - [Contrast-enhanced ultrasound in the diagnosis of hepatocellular carcinoma. Yes, it is possible]. PMID- 22300966 TI - [Spontaneous hematoma of the atrial wall]. AB - The clinical signs of heart masses tend to be nonspecific, generally depending more on their repercussions on heart function caused by their location rather than on their type. Imaging techniques make it possible to limit the differential diagnosis of heart masses based on their location, morphology, and characteristics of echogenicity, density, or intensity, depending on the technique used to study them. We present the case of a woman with squeezing mid chest pain irradiating to her shoulder and positive cardiac markers in whom a left atrial mass was identified at echocardiography. This finding was confirmed at chest CT. The signs at chest CT were compatible with a mural hematoma and this diagnosis was confirmed after intraoperative biopsy. PMID- 22300967 TI - [Noninvasive imaging techniques to study coronary artery aneurysms]. AB - Given the growing evidence about the use of membrane-covered stents to treat coronary artery aneurysms, it is fundamental to know the exact anatomy of the aneurysm to enable patients to be selected correctly. Invasive heart catheterization has limitations for diagnostic purposes and can underestimate the size of the aneurysm. In this article, we review the noninvasive diagnostic imaging techniques for the study of coronary artery aneurysms, illustrating the usefulness of each technique. PMID- 22300968 TI - Abnormal methylation of KCNQ1OT1 and differential methylation of H19 imprinting control regions in human ICSI embryos. AB - Summary To evaluate the integrity of genomic imprinting in embryos that failed to develop normally following intracytoplasmic sperm injection (ICSI), we analysed the methylation profile of H19 and KCNQ1OT1 imprinting control regions, H19DMR and KvDMR1 respectively, in high-grade blastocysts and in embryos that exhibited developmental anomalies. Significant hypomethylation of KvDMR1 was specifically observed in 5/5 atypical blastocysts graded BC, which probably reflected the vulnerability of the imprint in the inner cell mass during the methylation remodelling phase in the early embryo. In addition, KvDMR1 was hypermethylated in 2/5 CC graded atypical blastocysts and in 2/8 embryos that exhibited developmental delay. H19DMR appeared differentially methylated in all groups of embryos. DNA methyltransfersase 1 (DNMT1) expression was similar in most of the tested embryos and could not account for the abnormal methylation patterns of KvDMR1 observed. PMID- 22300969 TI - Importation of Hyalomma marginatum, vector of Crimean-Congo haemorrhagic fever virus, into the United Kingdom by migratory birds. AB - Hyalomma marginatum ticks are an important vector of Crimean-Congo haemorrhagic fever virus which can result in a severe and potentially fatal disease in humans. Given the continued emergence of clinical cases in Eurasia and focalised upsurges of H. marginatum populations in Europe, it seemed prudent to assess the potential of this vector species to be introduced into the United Kingdom. Immature forms of H. marginatum are frequent ectoparasites of passerine birds many of which migrate from Africa to the UK each spring. Incoming birds were inspected for ticks during the spring migration in 2010 and 2011. A total of 68 ticks was collected from 971 birds (29 bird species), 21% (14) of the ticks were identified as H. marginatum. Oenanthe oenanthe (Northern wheatear) and Sylvia communis (Whitethroat) were found to be infested by this tick in both years and with multiple ticks. Single specimens were also removed from Acrocephalus schoenobaenus (Sedge warbler) and Phoenicurus phoenicurus (Common redstart) in 2010. This study provides the first contemporary evidence for substantial importation of this tick species into the UK. PMID- 22300970 TI - Sudden unexpected death on fingolimod. PMID- 22300971 TI - Impact of pregnancy on conversion to clinically isolated syndrome in a radiologically isolated syndrome cohort. AB - BACKGROUND: In multiple sclerosis (MS), the relapse rate declines during pregnancy and increases during the first three months post-partum before returning to the pre-pregnancy rate. It is unknown whether pregnancy impacts the risk of clinical conversion in those within the presymptomatic period. OBJECTIVES: We investigate the impact of pregnancy on developing a clinical event in women diagnosed with radiologically isolated syndrome (RIS). METHODS: All women with RIS underwent clinical and radiological assessments as part of an observational, prospective, longitudinal study. Clinical and MRI outcomes were analyzed during and after pregnancy. Subjects who became pregnant were compared with an age-matched female RIS group who did not become pregnant during the same follow-up period. RESULTS: A total of 60 women with RIS were followed for up to seven years. Among them, seven became pregnant and were compared with 53 age matched control women with RIS who did not become pregnant during the observation period. A significantly shorter time of conversion to the first neurological event was observed in the pregnant group [15.3 months (10-18)] compared with the non-pregnant controls [35.7 months (8-76)], yielding an absolute difference of 20.4 months (p<0.05). The mean (SD) number of active lesions on a subsequent brain MRI scan was significantly higher in the pregnant group [3.2 (+/-1.7)] compared with the control group [1.8 (+/-0.6)]. CONCLUSIONS: The risk for clinical conversion from RIS to a clinical event and new MRI disease activity seems to be influenced by pregnancy. Pregnancy related physiological changes could operate as early as the presymptomatic period in patients with MS. PMID- 22300972 TI - Evaluation of performance of two different chest tubes with either a sharp or a blunt tip for thoracostomy in 100 human cadavers. AB - BACKGROUND: Emergent placement of a chest tube is a potentially life-saving procedure, but rate of misplacement and organ injury is up to 30%. In principle, chest tube insertion can be performed by using Trocar or Non-trocar techniques. If using trocar technique, two different chest tubes (equipped with sharp or blunt tip) are currently commercially available. This study was performed to detect any difference with respect to time until tube insertion, to success and to misplacement rate. METHODS: Twenty emergency physicians performed five tube thoracostomies using both blunt and sharp tipped tube kits in 100 fresh human cadavers (100 thoracostomies with each kit). Time until tube insertion served as primary outcome. Complications and success rate were examined by pathological dissection and served as further outcomes parameters. RESULTS: Difference in mean time until tube insertion (63 s vs. 59 s) was statistically not significant. In both groups, time for insertion decreased from the 1st to the 5th attempt and showed dependency on the cadaver's BMI and on the individual physician. Success rate differed between both groups (92% using blunt vs. 86% using sharp tipped kits) and injuries and misplacements occurred significantly more frequently using chest tubes with sharp tips (p = 0.04). CONCLUSION: Data suggest that chest drain insertion with trocars is associated with a 6-14% operator-related complication rate. No difference in average time could be found. However, misplacements and organ injuries occurred more frequently using sharp tips. Consequently, if using a trocar technique, the use of blunt tipped kits is recommended. PMID- 22300973 TI - The Wurzburg Anatomical Institute and its supply of corpses (1933-1945). AB - The Wurzburg Anatomical Institute was one of the largest institutions of its kind in early 20th-century Germany. Little is known so far, however, about its history in the Third Reich. This paper presents the first results of current research on the Institute's directors Hans Petersen (1925-1940) and Curt Elze (1940-1945) and the sources from which it received its corpses during that period. For both directors there is little evidence for a marked affinity to National-Socialist ideology but a substantial degree of opportunism emerges from the surviving sources, at least in the case of Elze. Elze not only joined the NSDAP, by his own admission, without strict necessity. He also did not protest when Werner Heyde, principal medical actor in the Nazi "euthanasia" program, supplied him with 80 corpses of men and women who clearly had been murdered with carbon monoxide. The Institute's supply of corpses is analyzed based on the registers of received corpses and other, supplementary sources. Before 1933, the Wurzburg Institute received most of its corpses from hospitals, old age homes. Between 1933 and 1945 some marked changes occurred. In particular, the number of corpses not only from psychiatric hospitals but also from other places of institutional care declined, presumably due, at least to a substantial degree, to "euthanasia". On the other hand, the number of corpses delivered from execution sites, prisons and Gestapo rose dramatically, reflecting the massive increase of the number of death sentences as well as, by all appearances, that of deaths from physical violence and torture in the prisons. PMID- 22300974 TI - 2012 ACCF/AATS/SCAI/STS expert consensus document on transcatheter aortic valve replacement. PMID- 22300975 TI - Use of clinical scores to detect dysglycaemia in overweight or obese women. AB - AIMS: To test if the use of either HbA(1c) level or calculated clinical scores including two published scores and a new score (the Bondy score) could help in selecting overweight or obese women who should benefit from oral glucose tolerance test (OGTT) to detect dysglycaemia. METHODS: The French Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) score and the Finnish Diabetes risk score (Findrisk) were calculated, whereas the Bondy score was built in a development sample of 698 women, BMI 37+/-7 kg/m(2), without known diabetes. External validation was performed in a validation sample of 212 women. RESULTS: A dysglycaemia (according to OGTT results, WHO criteria) was diagnosed in 161 (23.1%) patients. Sensitivity of fasting plasma glucose (FPG)>=6.1 mmol/l and HbA(1c)>=6% to identify dysglycaemia were respectively 27 and 41%. Areas under Receiver Operator Curve (AROC) of HbA(1c), DESIR score and Findrisk to detect dysglycaemia were 0.630 [95% confidence interval 0.580-0.680], 0.606 [0.561-0.652] and 0.635 [0.588-0.683], respectively. The Bondy score, based on age and waist circumference, had a better AROC (0.674 [0.626-0.721]) than the DESIR score (P<0.05). These performances were confirmed in the validation sample. Performing OGTT only in subjects with a Bondy score>=4 (41% of the sample) had a sensitivity of 61% and a better net benefit (0.128) than measuring FPG in all subjects (0.069). CONCLUSION: Performing OGTT in obese women selected on a simple clinical score is more sensitive to identify dysglycaemia than measuring FPG in all of them and may be cost-effective. PMID- 22300976 TI - Wnt signaling in the vertebrate central nervous system: from axon guidance to synaptic function. AB - Regulation of cell signaling by Wnt proteins is critical for the formation of neuronal circuits. Wnts modulate axon pathfinding, dendritic development, and synaptic assembly. Through different receptors, Wnts activate diverse signaling pathways that lead to local changes on the cytoskeleton or global cellular changes involving nuclear function. Recently, a link between neuronal activity, essential for the formation and refinement of neuronal connections, and Wnt signaling has been uncovered. Indeed, neuronal activity regulates the release of Wnt and the localization of their receptors. Wnts mediate synaptic structural changes induced by neuronal activity or experience. New emerging evidence suggests that dysfunction in Wnt signaling contributes to neurological disorders. In this article, the attention is focused on the function of Wnt signaling in the formation of neuronal circuits in the vertebrate central nervous system. PMID- 22300978 TI - Epithelial-mesenchymal transition: general principles and pathological relevance with special emphasis on the role of matrix metalloproteinases. AB - Epithelial-mesenchymal transition (EMT) is a physiological process in which epithelial cells acquire the motile and invasive characteristics of mesenchymal cells. Although EMT in embryonic development is a coordinated, organized process involving interaction between many different cells and tissue types, aspects of the EMT program can be inappropriately activated in response to microenvironmental alterations and aberrant stimuli, and this can contribute to disease conditions including tissue fibrosis and cancer progression. Here we will outline how EMT functions in normal development, how it could be activated in pathologic conditions-especially by matrix metalloproteinases-and how it may be targeted for therapeutic benefit. PMID- 22300977 TI - Building muscle: molecular regulation of myogenesis. AB - The genesis of skeletal muscle during embryonic development and postnatal life serves as a paradigm for stem and progenitor cell maintenance, lineage specification, and terminal differentiation. An elaborate interplay of extrinsic and intrinsic regulatory mechanisms controls myogenesis at all stages of development. Many aspects of adult myogenesis resemble or reiterate embryonic morphogenetic episodes, and related signaling mechanisms control the genetic networks that determine cell fate during these processes. An integrative view of all aspects of myogenesis is imperative for a comprehensive understanding of muscle formation. This article provides a holistic overview of the different stages and modes of myogenesis with an emphasis on the underlying signals, molecular switches, and genetic networks. PMID- 22300979 TI - On hormone action in the mammary gland. PMID- 22300980 TI - Ventral tegmental area neurons are either excited or inhibited by cocaine's actions in the peripheral nervous system. AB - Cocaine's multiple pharmacological substrates are ubiquitously present in the peripheral and central nervous system. Thus, upon its administration, cocaine acts in the periphery before directly acting in the brain. We determined whether cocaine alters ventral tegmental area (VTA) neuronal activity via its peripheral actions. In urethane-anesthetized rats, we recorded VTA neuron's responses to intravenous injections of two cocaine analogs: cocaine-hydrochloride (HCl, 0.25 mg/kg), which readily cross the blood-brain barrier (BBB), and cocaine-methiodide (MI, 0.33 mg/kg), which does not cross the BBB. Both cocaine analogs produced sustained changes in discharge rates that began 5 s after the initiation of a 10 s drug infusion. Within the first 90 s post-injection, the magnitudes of neuronal responsiveness of both cocaine analogs were comparable, but later the effects of cocaine-HCl were stronger and persisted longer than those of cocaine-MI. The proportion of neurons responsive to cocaine-HCl was twice that of cocaine-MI (74% and 35%, respectively). Both analogs also differed in their response onsets. Cocaine-MI rarely evoked responses after 1 min, whereas cocaine-HCl continued to evoke responses within 3 min post-injection. VTA neurons were either excited or inhibited by both cocaine analogs. Most units responsive to cocaine-MI, regardless of whether they were excited or inhibited, had electrophysiological characteristics of putative dopamine (DA) neurons. Units inhibited by cocaine-HCl also had characteristics of DA neurons, whereas excited neurons had widely varying action potential durations and discharge rates. Cocaine-MI and cocaine HCl each produced changes in VTA neuron activity under full DA receptor blockade. However, the duration of inhibition was shortened and the number of excitations increased, and they occurred with an earlier onset during DA receptor blockade. These findings indicate that cocaine acts peripherally with a short latency and alters the activity of VTA neurons before its well-known direct actions in the brain. PMID- 22300981 TI - Mephedrone ("bath salt") pharmacology: insights from invertebrates. AB - Psychoactive bath salts (also called meph, drone, meow meow, m-CAT, bounce, bubbles, mad cow, etc.) contain a substance called mephedrone (4-methylcathinone) that may share psychostimulant properties with amphetamine and cocaine. However, there are only limited studies of the neuropharmacological profile of mephedrone. The present study used an established invertebrate (planarian) assay to test the hypothesis that acute and repeated mephedrone exposure produces psychostimulant like behavioral effects. Acute mephedrone administration (50-1000 MUM) produced stereotyped movements that were attenuated by a dopamine receptor antagonist (SCH 23390) (0.3 MUM). Spontaneous discontinuation of mephedrone exposure (1, 10 MUM) (60 min) resulted in an abstinence-induced withdrawal response (i.e. reduced motility). In place conditioning experiments, planarians in which mephedrone (100, 500 MUM) was paired with the non-preferred environment during conditioning displayed a shift in preference upon subsequent testing. These results suggest that mephedrone produces three behavioral effects associated with psychostimulant drugs, namely dopamine-sensitive stereotyped movements, abstinence-induced withdrawal, and environmental place conditioning. PMID- 22300982 TI - Interaction between the carbon monoxide and nitric oxide pathways in the locus coeruleus during fever. AB - We have documented that the locus coeruleus (LC), the main noradrenergic nucleus in the brain, is part of a thermoeffector neuronal pathway in fever induced by lipopolysaccharide (LPS). Following this pioneering study, we have investigated the role of the LC carbon monoxide (CO) and nitric oxide (NO) pathways in fever. Interestingly, despite both CO and NO are capable of activating the same intracellular target, soluble guanylate cyclase (sGC), our data have shown that LC CO is an antipyretic molecule, whereas LC NO is propyretic. Thus, aiming at further exploring the mechanisms underlying their anti- and propyretic properties, we investigated the putative interplay between the LC CO and NO pathways. Male Wistar rats were implanted with a guide cannula in the fourth ventricle (4V) and a temperature datalogger capsule in the peritoneal cavity. The animals were microinjected into the 4V with an inhibitor of heme oxygenase (HO) (ZnDPBG [zinc(II)deuteroporphyrin IX 2,4 bis ethylene glycol]), or a CO donor (CORM-2 [tricarbonyldichlororuthenium-(II)-dimer]), or an inhibitor of nitric oxide synthase (NOS) (l-NMMA [N(G)-monomethyl-L-arginine acetate]), or an NO donor (NOC12 [3-ethyl-3-(ethylaminoethyl)-1-hydroxy-2-oxo-1-triazene]), and injected with LPS (100 MUg/kg i.p.). Two hours later, the rats were decapitated, and the brains were frozen and cut in a cryostat. LC punches were processed to assess LC bilirubin and nitrite/nitrate (NOx) levels. Microinjection of ZnDPBG reduced LC bilirubin and increased LC NOx, whereas l-NMMA diminished LC NOx and reduced LC bilirubin. Furthermore, NOC12 caused an increase in LC bilirubin, whereas CORM-2 caused a reduction in LC NOx. These findings are consistent with the notion that in the LC during LPS fever the CO pathway downmodulates NOS activity and the NO pathway upmodulates HO activity, and, together with previous data, allow us to conjecture that LC CO blunts fever by downmodulating NOS (antipyretic property), LC NO upmodulates HO and sGC activities favoring the development of LPS fever (propyretic effect). PMID- 22300983 TI - Neuropeptide S promotes wakefulness through activation of the posterior hypothalamic histaminergic and orexinergic neurons. AB - In spite of the initial and pivotal findings that the newly identified neuropeptide S (NPS) promotes arousal associated with locomotor and anxiolytic like effects, the mechanisms through which NPS acts to modulate sleep-waking states remain unclear. The present study was undertaken to investigate in the rat the effects of i.c.v. injection of NPS on the EEG, sleep-wake cycle, and brain c Fos expression. NPS at 0.1 and 1 nmol increased significantly wakefulness (W) during the first 2 h (54.7 +/- 3.2 and 64.9 +/- 2.1 min, respectively, vs. 41.4 +/- 2.5 min seen with saline injections, P<0.01 and P<0.001), accompanied by an increase in EEG high frequency activities (14.5-60 Hz). In the meanwhile, slow wave sleep (SWS) and paradoxical sleep (PS) decreased significantly. Ex-vivo Fos immunohistochemistry in the posterior hypothalamus revealed that, as compared with saline-treated rats, NPS enhanced c-Fos expression in histaminergic neurons by 76.0% in the ventral tuberomammillary nucleus (TMN) and 57.8% in the dorsal TMN, and in orexinergic neurons by 28.2% in the perifornical nucleus (PeF), 24.3% in the dorsomedial hypothalamic nucleus (DMH), and 13.7% in the lateral hypothalamic area (LH) of the posterior hypothalamus. The NPS-induced c-Fos expression in histaminergic neurons and orexinergic neurons where NPS receptor (NPSR) mRNA is highly expressed, suggests that NPS activates histaminergic and orexinergic neurons to promote W. PMID- 22300984 TI - Epigenetic differences in normal colon mucosa of cancer patients suggest altered dietary metabolic pathways. AB - We have compared DNA methylation in normal colon mucosa between patients with colon cancer and patients without cancer. We identified significant differences in methylation between the two groups at 114 to 874 genes. The majority of the differences are in pathways involved in the metabolism of carbohydrates, lipids, and amino acids. We also compared transcript levels of genes in the insulin signaling pathway. We found that the mucosa of patients with cancer had significantly higher transcript levels of several hormones regulating glucose metabolism and significantly lower transcript levels of a glycolytic enzyme and a key regulator of glucose and lipid homeostasis. These differences suggest that the normal colon mucosa of patients with cancer metabolizes dietary components differently than the colon mucosa of controls. Because the differences identified are present in morphologically normal tissue, they may be diagnostic of colon cancer and/or prognostic of colon cancer susceptibility. PMID- 22300985 TI - Bral1: "Superglue" for the extracellular matrix in the brain white matter. AB - Bral1 is a link protein that stabilizes the binding between lecticans and hyaluronic acid and thus maintains the extracellular matrix assembly in the CNS. Bral1 is specifically located in the white matter around the nodes of Ranvier. Recent studies suggest its function in promoting saltatory neural conduction. This article reviews the current knowledge about the structure, expression and function of this link protein. PMID- 22300986 TI - PSA-NCAM: synaptic functions mediated by its interactions with proteoglycans and glutamate receptors. AB - Dynamic regulation of glycosylation of the neural cell adhesion molecule (NCAM) by an unusual large negatively charged polysialic acid (PSA) is the major prerequisite for correct formation of brain circuitries during development and for normal synaptic plasticity, learning and memory in the adult. Traditionally, PSA is viewed as a de-adhesive highly hydrated molecule, which interferes with cell adhesion and promotes cellular/synaptic dynamics by steric hindrance. Analysis of synaptic functions of PSA-NCAM highlighted additional features of this molecule. First, PSA promotes interaction of NCAM with heparan sulfate proteoglycans and thus stimulates synaptogenesis. Second, PSA-NCAM modulates glutamate receptors: it restrains activity of extrasynaptic GluN2B-containing NMDA receptors and facilitates activity of a subset of AMPA receptors. Perturbation in polysialylation and/or NCAM expression in mouse models recapitulates many symptoms of human brain disorders such as schizophrenia, depression, anxiety and Alzheimer's disease. PMID- 22300987 TI - Carboxy-terminus of CXCR7 regulates receptor localization and function. AB - Chemokine receptor CXCR7 is essential for normal development, and this receptor promotes initiation and progression of diseases including cancer and autoimmunity. To understand normal and pathologic functions of CXCR7 and advance development of therapeutic agents, there is a need to define structural domains that regulate this receptor. We generated mutants of CXCR7 with deletion of different lengths of the predicted intracellular tail and analyzed effects on CXCR7 signaling and function in cell-based assays. While wild-type CXCR7 predominantly localized to intracellular vesicles, progressive deletion of the carboxy terminus redistributed the receptor to the plasma membrane. Truncating the intracellular tail of CXCR7 did not alter binding to CXCL12, but mutant receptors had reduced scavenging of this chemokine. Using a firefly luciferase complementation system, we established that deletions of the carboxy terminus decreased basal interactions and eliminated ligand-dependent recruitment of the scaffolding protein beta-arrestin-2 to receptors. Deleting the carboxy terminus of CXCR7 impaired constitutive internalization of the receptor and reduced activation of ERK1/2 by CXCL12-CXCR7. Inhibiting dynamin, a molecule required for internalization of CXCR7, increased ligand-dependent association of the receptor with beta-arrestin-2 and enhanced activation of ERK1/2. These studies establish mechanisms of action for CXCR7 and establish the intracellular tail of CXCR7 as a critical determinant of receptor trafficking, chemokine scavenging, and signaling. PMID- 22300988 TI - Radiologic case study. Avulsion of the right adductor longus from the symphysis pubis. PMID- 22300990 TI - Telescopic mating technique for bulk allograft reconstruction. AB - Bulk allograft reconstruction plays an important role in limb-salvage reconstructive surgery but is complicated by nonunion in up to one-third of cases. Because allograft-host healing is mediated via creeping substitution, intimate bone contact is desirable. Intraoperative assessment and optimization of the allograft-host junction site using a conventional transverse osteotomy is challenging and may result in slight gapping. Speculatively, this may result in longer healing times and may contribute to the high rate of non-union. Minimizing the nonunion rate and time to union are of value. This article describes the telescopic mating technique, which allows for substantially greater bone contact across the allograft-host junction site. PMID- 22300991 TI - Minimally invasive hip surgery. PMID- 22300992 TI - Strategies for the management of rheumatoid arthritis. AB - Rheumatoid arthritis is a chronic, systemic inflammatory autoimmune disease that, untreated, can lead to permanent joint damage, decrease in quality of life, and disability. Health care professionals play a vital role in caring for patients with rheumatoid arthritis. The therapeutic possibilities in the management of rheumatoid arthritis have changed, with newer biologic therapies that target the inflammatory cascade seen in rheumatoid arthritis. As new treatments become increasingly available, it is important for health care professionals to stay informed. This article provides physicians with a review of biologic therapies currently used for the treatment of rheumatoid arthritis and describe how those therapies are used to manage rheumatoid arthritis. PMID- 22300994 TI - Anterolateral approach for tibial pilon fractures. AB - The anterolateral approach to the tibia has been popularized for management of tibial pilon fractures. This approach offers the benefit of improved soft tissue coverage and the potential for a lower rate of wound-healing complications by avoiding incision placement over the subcutaneous border of the tibia. Although the fracture pattern dictates specific plate use, antomically designed anterolateral plates are useful for fixation of common fracture patterns. Additional exposures may be required to address other areas of the fracture, such as the medial malleolus, which cannot be accessed through this approach. PMID- 22300995 TI - Diagnosis of periprosthetic joint infection: the utility of a simple yet unappreciated enzyme. PMID- 22300996 TI - Bankart repair. PMID- 22300997 TI - Monteggia fractures in pediatric and adult populations. AB - A Monteggia fracture is a fracture of the proximal ulna coupled with a radial head dislocation. These fractures are an uncommon class of forearm fractures. Numerous classification systems have been developed to characterize these fractures, with the Bado classification being the most common. Elbow radiographs are the primary diagnostic modality, demonstrating dislocation when a line drawn extending through the radial head from the radial shaft does not penetrate the capitellum in all views. Notable differences exist in the prevalence, treatment, and outcomes of Monteggia fractures for pediatric and adult patient populations, with adolescents often achieving a better prognosis. Nonoperative management with closed reduction and cast immobilization often prevails in pediatric patients, dictated by the pattern of the ulnar fracture more so than the direction of the radial head dislocation. However, in adults, operative intervention is frequently indicated because angulation and shortening of the ulna often occur after closed reduction. Although the orthopedic community's understanding of these fractures has evolved, the fractures themselves remain a challenging clinical phenomenon. This article reviews the relevant anatomy and pathogenesis, classification, clinical presentation, diagnostic studies, management, outcomes, and complications of Monteggia fractures in children and adults. PMID- 22300999 TI - Silver nanoparticles/multiwalled carbon nanotube/polyaniline film for amperometric glutathione biosensor. AB - A new silver nanoparticles (AgNPs)/carboxylated multiwalled carbon nanotubes (c MWCNT)/polyaniline (PANI) film has been synthesized on Au electrode using electrochemical techniques. The enzyme glutathione oxidase (GSHOx) (EC 1.8.3.3) was immobilized covalently on the surface of AgNPs/c-MWCNT/PANI/Au electrode to construct the glutathione biosensor. The modified electrode was characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and Fourier transform infrared (FTIR) spectrophotometry. The biosensor showed optimum response within 4s at +0.4V vs. Ag/AgCl, pH 6.0 and 35 degrees C, with a linear working range of 0.3-3500 MUM and a detection limit of 0.3 MUM. The glutathione biosensor was employed for measurement of glutathione content in hemolysated erythrocyte (RBC). The sensor was evaluated with 97.77% and 99.16% recovery of added glutathione in hemolysated RBC and 2.4% and 6.3% within and between batch coefficients of variation (CVs) respectively. The enzyme electrode lost 50% of its initial activity after 300 uses over a period of 3 months, when stored at 4 degrees C. The biosensor has the advantages over earlier biosensors in terms of greater stability, lower response time and no interference by a number of RBC hemolysate substances. PMID- 22301000 TI - Thermal stability and enzymatic activity of RNase A in the presence of cationic gemini surfactants. AB - The thermal stability and enzymatic activity of bovine pancreatic ribonuclease A (RNase A) have been investigated in the presence of a homologous series of cationic gemini surfactants (alkanediyl-alpha,omega-bis(hydroxyethyl methyl hexadecyl ammonium bromide)). UV, circular dichorism and fluorescence spectroscopies have been used for this study. The denaturation curves at various surfactant concentrations were analyzed on basis of a two-transition model to obtain values of T(m) (temperature at the midpoint of denaturation) and DeltaH(m) (enthalpy change at T(m)) of each transition. The main conclusion of this study is that these cationic gemini surfactants slightly activate and stabilize RNase A below their critical micelle concentrations at pH 5.0. The cationic gemini surfactant with the shorter spacer interacts more efficiently with RNase A than those with longer spacers. PMID- 22301001 TI - Modification of chitosan membrane with poly(vinyl alcohol) and biocompatibility evaluation. AB - This work aimed to overcome chitosan (CS) membrane' drawbacks: mainly stiffness and hydrophobic surface by adding poly(vinyl alcohol) (PVA) and evaluate their biocompatibility. The chemical structure, crystalline and thermal properties were studied by FT-IR, XRD and DSC. The mechanical properties and wettability of CS/PVA membranes were studied by tensile test and static contact angle measurement. In vitro biocompatibility was also evaluated by MTS cytotoxicity assay and SEM examination. The results suggest that adding PVA into CS membrane could greatly improve CS membrane's flexibility and wettability. All the membranes prepared were biocompatible and have potential applications in GTR technology. PMID- 22301002 TI - Anti-hepatoma activity in mice of a polysaccharide from the rhizome of Anemone raddeana. AB - A neutral polysaccharide fraction (ARP) prepared from the rhizome of Anemone raddeana was tested for its anticancer activity in H22 tumor-bearing mice by oral administration. ARP could not only significantly inhibit the growth of H22 transplantable tumor, but also remarkably promote splenocytes proliferation, NK cell and CTL activity, as well as serum IL-2 and TNF-alpha production in tumor bearing mice. In addition, ARP treatment to tumor bearing mice had no toxicity to body weight, the liver and kidney. Moreover it could reverse the hematological parameters induced by 5-fluorouracil (5-FU) to near normal. The above results suggested that the antitumor activity of ARP might be achieved by improving immune response, and they could act as antitumor agent with immunomodulatory activity. PMID- 22301003 TI - In vitro and in vivo evaluation of oridonin-loaded long circulating nanostructured lipid carriers. AB - The purpose of this study was to develop poly(ethylene glycol)-coated nanostructured lipid carriers (PEG-NLC) for parenteral delivery of oridonin (ORI) to prolong drug circulation time in blood. Oridonin-loaded PEG-NLC (ORI-PEG-NLC) consisting of PEG(2000)-stearate, glycerol monostearate and medium chain triglycerides were prepared by emulsion-evaporation and low temperature solidification technique. Oridonin-loaded NLC (ORI-NLC) were also prepared as control. ORI-PEG-NLC were observed by transmission election microscope and the morphology was in rotiform shape. The mean particle size of ORI-PEG-NLC was 329.2 nm and entrapment efficacy was 71.18%. The results of differential scanning calorimetry and X-ray diffraction revealed a low-crystalline structure of ORI and verified the incorporation of ORI into the nanoparticles. In vitro drug release of ORI-PEG-NLC exhibited biphasic drug release patterns with burst release initially and prolonged release afterwards. Pharmacokinetic analysis showed that the mean residence time of ORI-PEG-NLC was prolonged and AUC (area under tissue concentration-time curve) value was also improved compared with ORI-NLC and ORI solution. In conclusion, ORI-PEG-NLC could be a potential carrier to get prolonged retention time of oridonin in blood. PMID- 22301004 TI - Effect of PVA on the gel temperature of MC and release kinetics of KT from MC based ophthalmic formulations. AB - The effect of molecular weight of poly(vinyl alcohol) (PVA) and sodium chloride on the gelation temperature of methylcellulose (MC) was studied with the objective to develop a MC based formulation for sustained delivery of ketorolac tromethamine a model ophthalmic drug. Pure MC showed sol-gel transition at 61.2 degrees C. In order to reduce the gelation temperature of MC and to increase the drug release time, PVA was used. Different techniques such as test tube tilting method, UV-vis spectroscopy, viscometry and rheometry were used to measure gelation temperature of all the binary combinations of MC and PVA. It was observed that the gelation temperature of MC was reduced with the addition of 4% PVA and also the extent of reduction of the gelation temperature of MC was dependent on the molecular weight of PVA. The strong interactions between MC and PVA molecules were established using Fourier transform infrared spectroscopy. To study the in vitro drug release properties of the MC-PVA binary combinations, 6% sodium chloride was used to reduce the gelation temperature further up to physiological temperature. It was observed that the drug release time increased from 5 to 8h with the increase of molecular weight of PVA from 9*10(3) to 1.3*10(5) and this was due to the higher viscosity, better gel strength and greater interactions between the drug and PVA molecules in case of PVA (1.3*10(5)) compared to PVA (9*10(3)). In order to have an idea about the nature of interactions between the functional moieties of the drug and the polymer unit of PVA, a theoretical study was carried out. PMID- 22301005 TI - Prognosis of 2009 A(H1N1) influenza in hospitalized pregnant women in a context of early diagnosis and antiviral therapy. AB - BACKGROUND: Initial reports suggested that novel A(H1N1) influenza virus (2009 A[H1N1]v) infection was significantly more severe in pregnant than in non pregnant women. In Spain, antiviral therapy was recommended for pregnant women from the beginning of the 2009 pandemic. METHODS: The prospective cohort study included consecutive pregnant and non-pregnant women of reproductive age with a proven diagnosis of 2009 A(H1N1)v admitted to any of the 13 participating Spanish hospitals between 12 June and 10 November 2009. RESULTS: In total, 98 pregnant and 112 non-pregnant women with proven 2009 A(H1N1)v hospitalized during the study period were included. Influenza was more severe among non-pregnant patients than pregnant patients with respect to outcomes of both intensive care unit admission (18% versus 2%; P<0.001) and death (5 versus 0; P=0.06). Pregnant women had fewer associated comorbid conditions other than pregnancy (18% versus 44%; P<0.001); they were also admitted earlier than non-pregnant women (median days since onset of symptoms: 2 versus 3; P<0.001) and a higher percentage received early antiviral therapy (41% versus 28%; P=0.03). Neither a multivariate nor a matched cohort analysis found pregnancy to be associated with greater severity than that associated with hospitalized, seriously ill non-pregnant women. CONCLUSIONS: 2009 A(H1N1)v influenza was not associated with worse outcomes in hospitalized pregnant women compared with non-pregnant ones of reproductive age in a context of early diagnosis and antiviral therapy. PMID- 22301006 TI - In vivo priming of IL-17(+) uveitogenic T cells is enhanced by Toll ligand receptor (TLR)2 and TLR4 agonists via gammadelta T cell activation. AB - We investigated the in vivo priming of IL-17(+) autoreactive T cells in experimental autoimmune uveitis-prone C57BL/6 (B6) and B10RIII mice using a combination of approaches, including limiting dilution assay. High numbers of in vivo primed IL-17(+) interphotoreceptor retinoid-binding protein (IRBP)-specific T cells were found in mice immunized with a uveitogenic peptide emulsified in CFA, but not the same peptide emulsified in IFA. Both in vitro and in vivo, at least part of the effect of mycobacterial antigen in CFA could be replaced by TLR2 or TLR4 ligands. TCR-delta(-/-) mice immunized with IRBP peptide in CFA generated significantly lower numbers of IL-17(+) T cells than immunized wild type B6 mice. Administration of a small number of activated gammadelta T cells to TCR-delta(-/-) mice significantly increased the number of IL-17(+), but not IFN gamma(+), IRBP-specific T cells in these mice. gammadelta T cells from CFA- or IFA plus TLR ligand-treated mice were activated and injection of naive TCR-delta( /-) mice with gammadelta T cells from TLR ligand-treated, but not untreated, B6 mice promoted the in vivo priming of IL-17(+) IRBP-reactive T cells. In conclusion, in vivo priming of IL-17(+) uveitogenic T cells in mice is significantly affected by TLR ligation, and is also influenced by activated gammadelta T cells. PMID- 22301007 TI - Science education for tomorrow's health professionals. PMID- 22301008 TI - Biomechanics of human movement and its clinical applications. AB - All life forms on earth, including humans, are constantly subjected to the universal force of gravitation, and thus to forces from within and surrounding the body. Through the study of the interaction of these forces and their effects, the form, function and motion of our bodies can be examined and the resulting knowledge applied to promote quality of life. Under gravity and other loads, and controlled by the nervous system, human movement is achieved through a complex and highly coordinated mechanical interaction between bones, muscles, ligaments and joints within the musculoskeletal system. Any injury to, or lesion in, any of the individual elements of the musculoskeletal system will change the mechanical interaction and cause degradation, instability or disability of movement. On the other hand, proper modification, manipulation and control of the mechanical environment can help prevent injury, correct abnormality, and speed healing and rehabilitation. Therefore, understanding the biomechanics and loading of each element during movement using motion analysis is helpful for studying disease etiology, making decisions about treatment, and evaluating treatment effects. In this article, the history and methodology of human movement biomechanics, and the theoretical and experimental methods developed for the study of human movement, are reviewed. Examples of motion analysis of various patient groups, prostheses and orthoses, and sports and exercises, are used to demonstrate the use of biomechanical and stereophotogrammetry-based human motion analysis studies to address clinical issues. It is suggested that further study of the biomechanics of human movement and its clinical applications will benefit from the integration of existing engineering techniques and the continuing development of new technology. PMID- 22301009 TI - New concepts of science and medicine in science and technology studies and their relevance to science education. AB - Science education often adopts a narrow view of science that assumes the lay public is ignorant, which seemingly justifies a science education limited to a promotional narrative of progress in the form of scientific knowledge void of meaningful social context. We propose that to prepare students as future concerned citizens of a technoscientific society, science education should be informed by science, technology, and society (STS) perspectives. An STS-informed science education, in our view, will include the following curricular elements: science controversy education, gender issues, historical perspective, and a move away from a Eurocentric view by looking into the distinctive patterns of other regional (in this case of Taiwan, East Asian) approaches to science, technology, and medicine. This article outlines the significance of some major STS studies as a means of illustrating the ways in which STS perspectives can, if incorporated into science education, enhance our understanding of science and technology and their relationships with society. PMID- 22301010 TI - Physical aspects of medical science. AB - Physical aspects of medical science involve making physical models, physical approaches, and measurements by physical instruments. Among these, the physical approach is the most important for an exact elucidation of the physiological function of living materials. What is a physical approach? In the first step, the molecular mechanism of visual transduction will be demonstrated by considering the physical characteristics of diffusion of second messengers. In the next step, I will consider how frequency modulation-type impulse signaling is converted from amplitude modulation-type electric signaling. In the last section, I will discuss how impulse signaling (i.e., the train of action potentials) is processed by the neural network in the brain and eventually is recognized in the frontal cortex using near infrared spectroscopy. In order to obtain such a physical model of vision, many physical concepts are used, such as light reflex, energy transduction, diffusion of molecules, threshold, the Coulomb interaction, light absorption, and cluster analysis. Among them, the Coulomb interaction, light absorption, and diffusion of molecules are three essential keywords for the physical process. PMID- 22301011 TI - Physics teaching in the medical schools of Taiwan. AB - We describe and analyze the statistics of general physics and laboratory courses in the medical schools of Taiwan. We explore the development of the general physics curriculum for medical students of Taiwan. Also, an approach to designing a general physics course in combination with its application to medical sciences is proposed. We hope this preliminary study can provide a useful reference for physics colleagues in the medical schools of Taiwan to revolutionize the dynamics of teaching physics to the medical students of Taiwan. PMID- 22301012 TI - Applying principles from "Scientific Foundations for Future Physicians" to teaching chemistry in the department of medicine at Chang Gung University. AB - Similar to the current trends in America that were recognized by the Association of American Medical College and the Howard Hughes Medical Institute in their 2009 report titled "Scientific Foundations for Future Physicians," Taiwanese medical students are lacking in their ability to apply their knowledge of basic sciences to real-life situations. The report recommended developing a competency-based approach to learning and also called for an increase in integrated and interdisciplinary courses in the education of medical students. Such a class, which would encourage students to look at biological concepts through chemical and physical principles, has been developed at Chang Gung University, and it strives to develop the medical student's ability to work in groups, think critically, and clearly and convincingly present ideas. The course requires students to present biological topics in groups after working closely with a teacher, and it trains the students to identify useful and trustworthy sources, to constructively criticize each other, and work together to present a cohesive and informative presentation for their peers. From my teaching experience, classes such as this have led me to conclude that the teacher's role does not simply encompass that of the informant, but also the facilitator of the academic success of the students, and this has led me to create certain class policies for teachers that help students of any field success in class. PMID- 22301013 TI - Teaching professionalism in science courses: anatomy to zoology. AB - Medical professionalism is reflected in attitudes, behaviors, character, and standards of practice. It is embodied by physicians who fulfill their duties to patients and uphold societies' trust in medicine. Professionalism requires familiarity with the ethical codes and standards established by international, governmental, institutional, or professional organizations. It also requires becoming aware of and responsive to societal controversies. Scientific uncertainty may be used to teach aspects of professionalism in science courses. Uncertainty about the science behind, and the health impacts of, climate change is one example explored herein that may be used to teach both professionalism and science. Many medical curricula provide students with information about professionalism and create opportunities for students to reflect upon and strengthen their individually evolving levels of professionalism. Faculties in basic sciences are rarely called upon to teach professionalism or deepen medical students understanding of professional standards, competencies, and ethical codes. However they have the knowledge and experience to develop goals, learning objectives, and topics relevant to professionalism within their own disciplines and medical curricula. Their dedication to, and passion for, science will support basic science faculties in designing innovative and effective approaches to teaching professionalism. This paper explores topics and formats that scientists may find useful in teaching professional attitudes, skills, and competencies in their medical curriculum. It highlights goals and learning objectives associated with teaching medical professionalism in the basic sciences. PMID- 22301014 TI - The process of decline in advanced activities of daily living: a qualitative explorative study in mild cognitive impairment. AB - BACKGROUND: The notion of "minimal impairment in instrumental activities of daily living (i-ADL)" is important in the diagnosis of mild cognitive impairment (MCI), but is presently not adequately operationalized. ADL is stratified according to difficulty, complexity, and also to vulnerability to early cognitive changes in a threefold hierarchy: basic activities of daily living (b-ADL), i-ADL, and advanced activities of daily living (a-ADL). This study aims to gain a deeper understanding of the functional decline in the process of MCI. METHODS: In a qualitative design, 37 consecutive patients diagnosed with amnestic (a)-MCI and their proxies were interviewed at two geriatric day hospitals. Constant comparative analysis was used for the analysis. RESULTS: The a-ADL-concept emerged as important in the diagnosis of MCI. All participants were engaged in a wide range of activities, which could be clustered according to the International Classification of Functioning, Disability and Health (ICF). Participants reported subtle difficulties in performance. A process of functional decline was identified in which adaptation and coping mechanisms interacted with the process of reduced skills, leading to an activity disruption and an insufficiency in functioning. CONCLUSION: This study asserts the inclusion of an evaluation of a ADL in the assessment of older persons. When evaluating ADL at three levels (b ADL, i-ADL, and a-ADL), all the activities one can perform in daily living are covered. PMID- 22301015 TI - [Intestinal pneumatosis]. PMID- 22301016 TI - Effects of anticoccidial and antibiotic growth promoter programs on broiler performance and immune status. AB - This study investigated the effects of various coccidiosis control programs in combination with antibiotic growth promoters (AGPs) on growth performance and host immune responses in broiler chickens. The coccidiosis programs that were investigated included in ovo coccidiosis vaccination (CVAC) with Inovocox or in feed medication with diclazuril as Clinacox (CLIN) or salinomycin (SAL). The AGPs were virginiamycin or bacitracin methylene disalicylate plus roxarsone. As a negative control, chickens were non-vaccinated and fed with non-supplemented diets (NONE). All animals were exposed to used litter from a commercial broiler farm with confirmed contamination by Eimeria parasites to simulate in-field exposure to avian coccidiosis. Broiler body weights in the CVAC group were greater at 14 and 32 days of age, but not at day 42, compared with the NONE, CLIN, and SAL groups. At day 14, the SAL group showed decreased body weight and reduced ConA-stimulated spleen cell proliferation compared with the CLIN and SAL groups. In contrast, at days 34 and 43, splenocyte proliferation was greater in the CVAC and CLIN groups compared with the NONE and SAL groups. Lymphocyte subpopulations and cytokine mRNA expression levels in the intestine and spleen were also altered by the denoted treatments. Collectively, these results suggest that in ovo coccidiosis vaccination or coccidiostat drug medication programs in combination with AGPs influences chicken growth and immune status in an Eimeria contaminated environment. PMID- 22301017 TI - [State of acute phase markers and oxidative stress in patients with kidney stones in the urinary tract]. AB - OBJECTIVE: This present study has aimed to assess the state of acute phase markers and oxidative stress in patients with kidney stones. MATERIAL AND METHODS: A prospective study was carried out on 100 patients with kidney stones and 25 healthy controls. Albumin, beta2 microglobulin, Gamma-glutamyl transpepsidase, Lactate dehydrogenase, Tumor necrosis factor alpha, Interleukin 1 and Interleukin-6 were evaluated as acute phase markers and lipid peroxidation products, Superoxide dismutase and Glutathione peroxidase levels acted as oxidative stress markers. RESULTS: An increase in renal cell damage markers as expressed by the beta2 microglobulin (p=0.04), albumin (p=0.004), Lactate dehydrogenase (p=0.001) and Gamma glutamyl transpepsidasa (p=0.01) was observed in the patient group. There was a direct correlation between levels of beta2 microglobulin and stone size (r=0.3, p=0.03). The association between stone size and cytokine activation was observed to be stronger in patients with staghorn calculi. In these patients, Tumor necrosis factor alpha (p=0.011), Interleukin 1 (p=0.004) and Interleukin 6 (p=0.004) were significantly higher. Patients with stones in the urinary tract showed data of significantly higher oxidative stress, expressed as an increase in levels of lipid peroxidation products (p=0.03) and a decrease in the antioxidant activity of Superoxide dismutase (p=0.03) and Glutathione peroxidase (p=0.002). CONCLUSIONS: Patients undergoing urolithiasis showed an elevation of acute phase markers, associated with oxidative stress as expressed by an increase in lipid peroxidation products and a decrease in the antioxidant enzyme activity. PMID- 22301018 TI - [Increased expression of hypoxia-inducible factor-1alpha and connective tissue growth factor accompanied by fibrosis in the rat testis of varicocele]. AB - OBJECTIVE: We investigated hypoxia inducible factor-1alpha (HIF-1alpha), connective tissue growth factor (CTGF) expression and fibrosis in the testis of rats with surgically induced varicocele. MATERIAL AND METHODS: A total of 47 adult male Sprague-Dawley rats were arranged in 3 groups, namely group 1 (varicocele operation 4 weeks ago, n=10; sham operation 4 weeks ago, n=5), group 2 (8 weeks, n=11; n=5), and group 3 (12 weeks, n=11; n=5). The rats in every group underwent bilateral orchiectomy 4, 8, and 12 weeks after the operations, respectively. HIF-1alpha and CTGF expression of both testes in group 3 were studied by real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Fibrotic change was assessed by quantitative image analysis. RESULTS: HIF-1alpha mRNA expression in testes tissues in varicocele operation and sham controls showed no significant differences in RT-PCR. However, CTGF mRNA expressions in left testes were found to be significantly different between varicocele operation and sham controls. HIF-1alpha staining was present in both testes of all specimens and CTGF staining was present in 10 left and 8 right testes of 11 specimens. However HIF-1alpha and CTGF staining were absent in control group. There were significant fibrotic changes of both testes in groups 2 and 3. There were significant differences in fibrotic change along the durations of surgical varicocele. CONCLUSIONS: This study reveals that experimental varicocele in the rat is associated with HIF-1alpha and CTGF expression and it is accompanied by fibrotic change in the testis. PMID- 22301019 TI - First evaluation of an improved assay for molecular genetic detection of tuberculosis as well as rifampin and isoniazid resistances. AB - The commercially available line probe assay MTBDRplus 2.0 (Hain Lifescience, Nehren, Germany) was evaluated for its ability to detect Mycobacterium tuberculosis complex (MTBC) and mutations conferring resistance to rifampin (RMP) and isoniazid (INH) directly in smear-negative and smear-positive pulmonary clinical specimens under routine laboratory conditions. A total of 348 samples originating from Moldova, a high-incidence country for tuberculosis (TB), were investigated. Two hundred fifty-seven (73.9%) were smear negative, 12 samples were excluded, and 81 (23.3%) were smear positive. Two DNA extraction methods were applied. Compared to culture and clinical data as the reference standard (adapted from Vadwai V et al., J. Clin. Microbiol. 49:2540-2545, 2011), overall sensitivity and specificity were 87.6 and 99.2%, respectively. One hundred four of the 257 smear-negative samples turned out to be culture positive, and 20 were MTBC culture negative but were positive based on clinical symptoms. The combined sensitivity and specificity in the subgroup of smear-negative samples were calculated to be 79.8 and 99.2%, respectively. MTBDRplus 2.0 detected RMP and INH resistance with sensitivity and specificity of 94.3 and 96.0%, respectively. In conclusion, the MTBDRplus 2.0 assay is a rapid and highly sensitive test for the detection of M. tuberculosis strains from smear-positive and -negative clinical specimens and provides additional information on RMP and INH resistance status, which can easily be included in routine laboratory work flow. PMID- 22301020 TI - Evaluation of new biomarker genes for differentiating Haemophilus influenzae from Haemophilus haemolyticus. AB - PCR detecting the protein D (hpd) and fuculose kinase (fucK) genes showed high sensitivity and specificity for identifying Haemophilus influenzae and differentiating it from H. haemolyticus. Phylogenetic analysis using the 16S rRNA gene demonstrated two distinct groups for H. influenzae and H. haemolyticus. PMID- 22301021 TI - Quantitative real-time PCR for detection of Acinetobacter baumannii colonization in the hospital environment. AB - A real-time PCR assay was developed for detecting the presence of Acinetobacter baumannii on hospital equipment and compared to conventional bacterial culture using 100 hospital environmental samples. The real-time PCR detected contaminated surfaces in 4 h with high sensitivity (100%) compared to conventional culture. Thirty-eight percent of samples were positive by real-time PCR and negative by bacterial culture (false positives), possibly indicating the widespread presence of bacterial DNA that is not associated with viable bacteria. PMID- 22301022 TI - Species identification of clinical Prevotella isolates by matrix-assisted laser desorption ionization-time of flight mass spectrometry. AB - The performance of matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) for species identification of Prevotella was evaluated and compared with 16S rRNA gene sequencing. Using a Bruker database, 62.7% of the 102 clinical isolates were identified to the species level and 73.5% to the genus level. Extension of the commercial database improved these figures to, respectively, 83.3% and 89.2%. MALDI-TOF MS identification of Prevotella is reliable but needs a more extensive database. PMID- 22301023 TI - Human papillomavirus (HPV) DNA triage of women with atypical squamous cells of undetermined significance with cobas 4800 HPV and Hybrid Capture 2 tests for detection of high-grade lesions of the uterine cervix. AB - The triage of women with high-risk (HR) human papillomavirus (HPV)-positive smears for atypical squamous cells of undetermined significance (ASC-US) to colposcopy is now an integrated option in clinical guidelines. The performance of cobas 4800 HPV and that of Hybrid Capture 2 (HC2) for HR HPV DNA detection in cervical samples in PreservCyt were compared in 396 women referred to colposcopy for ASC-US. Of these, 316 did not have cervical intraepithelial neoplasia (CIN), 47 had CIN1, 29 had CIN2 or CIN3 (CIN2+), and 4 had CIN of unknown grade. HR HPV was detected in 129 (32.6%) and 149 (37.6%) samples with HC2 and cobas 4800 HPV, respectively (P = 0.15). The clinical sensitivities and specificities for detecting CIN2+ were 89.7% (95% confidence interval [CI], 72.8 to 97.2%) and 66.7% (95% CI, 61.7 to 71.3%) with cobas 4800 HPV and 93.1% (95% CI, 77.0 to 99.2%) and 72.2% (95% CI 67.4 to 76.5%) with HC2. The performance of cobas 4800 HPV was similar to that of HC2 for identifying women with ASC-US who would benefit the most from colposcopy. PMID- 22301024 TI - Performance of tuberculosis drug susceptibility testing in U.S. laboratories from 1994 to 2008. AB - We present a statistical summary of results from the Model Performance Evaluation Program (MPEP) for Mycobacterium tuberculosis Drug Susceptibility Testing, 1994 to 2008, implemented by the U.S. Centers for Disease Control and Prevention (CDC). During that period, a total of 57,733 test results for culture isolates were reported by 216 participating laboratories for the first-line antituberculosis drugs used in the United States-isoniazid (INH), rifampin (RMP), ethambutol (EMB), and pyrazinamide (PZA). Using Clinical Laboratory and Standards Institute (CLSI)-recommended concentrations for one or more of three methods, agar proportion (AP), BACTEC460 (Bactec), and MGIT-960 (MGIT), yielded overall agreement of 97.0% for first-line drugs. For susceptible strains, agreement was 98.4%; for resistant strains, agreement was 91.0%, with significantly lower accuracy (chi-square test, P < 0.0001). For resistant strains, overall agreement by methods was 91.3% for AP, 93.0% for Bactec, and 82.6% for MGIT and by drugs was 92.2% for INH, 91.5% for RMP, 79.0% for EMB, and 97.5% for PZA. For some strains, performance by method varied significantly. Use of duplicate strains in the same shipment and repeat strains over time revealed consistent performance even for strains with higher levels of interlaboratory discordance. No overall differences in performance between laboratories were observed based on volume of testing or type of facility (e.g., health department, hospital, independent). By all methods, decreased performance was observed for strains with low-level INH resistance, RMP resistance, and EMB-resistant strains. These results demonstrate a high level of performance in detection of drug-resistant M. tuberculosis in U.S. laboratories. PMID- 22301025 TI - Detection of galactomannan in bronchoalveolar lavage fluid samples of patients at risk for invasive pulmonary aspergillosis: analytical and clinical validity. AB - Invasive pulmonary aspergillosis (IPA) is frequent and often fatal in immunosuppressed patients. Timely diagnosis of IPA improves survival but is difficult to make. We examined the analytical and clinical validity of galactomannan (GM) testing of bronchoalveolar lavage (BAL) fluid in diagnosing IPA in a mixed population by retrospectively reviewing records of 251 consecutive at-risk patients for whom BAL fluid GM testing was ordered. The performance of the enzyme immunoassay was evaluated by using a range of index cutoffs to define positivity. Three samples were associated with proven IPA, 56 were associated with probable IPA, 63 were associated with possible invasive fungal disease (IFD), and 129 were associated with no IFD. Using a BAL fluid GM index of >=0.8 (optimal optical density [OD] index cutoff identified by a receiver operating characteristic curve), the sensitivity in diagnosing proven and probable IPA was 86.4%, and the specificity was 90.7%. At this cutoff, positive and negative predictive values were 81% and 93.6%, respectively. However, an OD index value of >=3.0 corresponded to a 100% specificity, thus ruling the disease in, irrespective of the pretest probability. Conversely, an OD index cutoff of <0.5 corresponded to a high sensitivity, virtually always ruling the disease out. For all values in between, the posttest probability of IPA depends largely on the prevalence of disease in the at-risk population and the likelihood ratio of the OD index value. Detection of GM in BAL fluid samples of patients at risk of IPA has an excellent diagnostic accuracy provided results are interpreted in parallel with clinico-radiological findings and pretest probabilities. PMID- 22301026 TI - Identification of hepatitis C virus transmission using a next-generation sequencing approach. AB - Here, we describe a transmission event of hepatitis C virus (HCV) among injection drug users. Next-generation sequencing (NGS) was used to assess the intrahost viral genetic variation. Deep amplicon sequencing of HCV hypervariable region 1 allowed for a detailed analysis of the structure of the viral population. Establishment of the genetic relatedness between cases was accomplished by phylogenetic analysis. NGS is a powerful tool with applications in molecular epidemiology studies and outbreak investigations. PMID- 22301027 TI - Glutamate dehydrogenase is highly conserved among Clostridium difficile ribotypes. AB - gluD was highly conserved and glutamate dehydrogenase (GDH) was readily expressed in vitro by all 77 Clostridium difficile ribotypes assayed. All ribotypes, including ARL 002, ARL 027, and ARL 106, were reactive in assays that detect C. difficile GDH. PMID- 22301028 TI - Molecular markers for detection and differentiation of Plasmodium falciparum and Plasmodium vivax in human blood samples by pyrosequencing. AB - PCR amplification coupled with pyrosequencing was used to measure molecular markers that could be used to detect and differentiate Plasmodium falciparum and Plasmodium vivax in human blood samples. The detection rates were in agreement with the results of Giemsa-stained film microscopy, which is the current gold standard for detection. This method provides an exciting alternative for malaria diagnosis. PMID- 22301029 TI - An invasive Haemophilus haemolyticus isolate. PMID- 22301030 TI - Evidence implicating Thamnostylum lucknowense as an etiological agent of rhino orbital mucormycosis. AB - In this report, we present a case of rhino-orbital mucormycosis in a 57-year-old female with poorly controlled diabetes mellitus. The only mold cultured at 25 degrees C, 37 degrees C, and 40 degrees C from a specimen of the nasal crust was identified phenotypically and independently using nuclear ribosomal DNA sequence data as Thamnostylum lucknowense. To our knowledge, this report presents the first data implicating this mucoraceous fungus as a mycotic agent of human infection. PMID- 22301031 TI - Childhood antecedents to adult cardiovascular disease. AB - Through research in the prevention and treatment of adult diseases, it has become clear that many adult diseases have their origins in childhood. As illustrated in this review, these antecedents are largely a function of the nutrition, physical activity, and habits of developing children. There is also increasing evidence that chronic and toxic levels of stress can play a significant role not only in the development of mental and behavioral conditions but in the developmental pathways that lead to a number of chronic physical health conditions. Internists, family medicine physicians, and medicine-pediatrics physicians generally are comfortable managing patients with a number of cardiovascular risk factors or conditions. Although pediatric clinical guidelines have recommended universal screening for hypertension since 1977 and targeted screening for dyslipidemia since 1992 and type 2 DM since 2000, this screening is not yet common practice in general pediatrics. As the population of children and youth with risk factors for metabolic syndrome--hypertension, dyslipidemia, and type 2 DM--increases as a result of the obesity epidemic, pediatricians will have to screen routinely, and diagnose and treat these conditions in the primary care setting. Pediatric residency programs and continuing medical education programs will have to provide knowledge and clinical training in the management of these conditions before primary care pediatricians are comfortable treating children and youth with multiple cardiovascular conditions. PMID- 22301032 TI - Pediatric systemic lupus erythematosus: more than a positive antinuclear antibody. AB - Based on strong research evidence and consensus, the most common disease manifestations at diagnosis of pSLE are constitutional symptoms, arthritis, and malar rash. Based on some research evidence and consensus, patients with pSLE tend to have major organ system involvement (renal/central nervous system) and a greater disease burden compared with adults. Despite these findings, mortality is low. Based on some research evidence and consensus, the diagnosis of pSLE is unlikely if the ANA is negative, and most patients with SLE have a positive ANA at a titer >=1:160. Based on strong research evidence, both MMF and cyclophosphamide can be used for induction therapy in class III and IV lupus nephritis. Based on strong research evidence, patients with SLE and anticardiolipin antibodies or LA have a two and six times greater risk of venous thrombosis, respectively, compared with patients with SLE without antiphospholipid antibodies. Based on strong research evidence, patients with pSLE have a higher risk for subclinical atherosclerosis when there is weight adjusted prednisone use, azathioprine use, increasing age, male gender, high BMI, abnormal creatinine clearance, and elevated lipoprotein(a) levels. PMID- 22301033 TI - Consultation with the specialist: thyroid nodules. AB - Based on strong research evidence, thyroid nodules in children and teenagers are more likely to be malignant than in adults. Based on strong research evidence, a history of ionizing radiation to the head or neck is an independent risk factor for the development of thyroid malignancies. There is strong research evidence, including a recent meta-analysis, supporting the use of fine-needle aspiration biopsy in the evaluation of all pediatric and adolescent patients presenting with a thyroid nodule. The surgical management and postoperative care of pediatric and adolescent patients who have well-differentiated thyroid carcinomas remains controversial, because the rarity of the disease limits the ability to conduct randomized, prospective research studies. Numerous studies have demonstrated that, despite presenting with more advanced disease, pediatric and adolescent patients with thyroid carcinoma have a higher survival rate than adults. The American Thyroid Association has issued strong evidence-based recommendations for the management of medullary thyroid carcinoma, including RET mutation testing and early prophylactic total thyroidectomy in children with high-risk mutations. PMID- 22301034 TI - Complementary, holistic, and integrative medicine: Crohn disease. AB - Although the use of CAM in pediatric CD is common, quality evidence-based research is limited. There is clearly a need for further randomized controlled trials. The role of psychosocial distress in children with CD should not be overlooked and thus biobehavioral techniques should be considered and incorporated when possible. Considering the potential for growth failure and need for surgical intervention in CD, any CAM therapies that are not harmful should be used only in combination with conventional medical treatment. The importance of all health care providers partnering with their patients and asking about CAM use, as well as maintaining an awareness of efficacy, safety, harm, drug supplement interactions, and appropriate referral sources, should be kept in mind when caring for those afflicted with this chronic disease. PMID- 22301035 TI - An infant who has dome-shaped papules. AB - JXG is a benign disorder of early childhood and primarily occurs in infants and children <2 years of age. It is characterized by solitary or multiple yellow-red nodules on the skin and, rarely, in other organs. The clinical diagnosis of solitary cutaneous JXG usually requires confirmation by biopsy. Referral to a dermatologist should be obtained to exclude other disorders if multiple lesions are present. Clinicians should rule out ocular lesions with referral to an ophthalmologist if the patient is <2 years of age and has multiple lesions of JXG. If ophthalmologic consultation reveals no ocular lesions, screening every 6 months for the first 2 years of life is advised. PMID- 22301036 TI - Index of suspicion. Case 1: Lymphadenopathy, prolonged hematuria, proteinuria, and weight loss in a teenage boy. Case 2: Red, Swollen, painful eye in a 12-year old boy with methylmalonic acidemia. Case 3: Ptosis and diplopia after a respiratory infection in a 7-year-old girl. PMID- 22301037 TI - Ethics for the pediatrician: a brave new pediatrics? Managing the desire for better children through biotechnological enhancement. PMID- 22301038 TI - The effect of academic "misrepresentation" on residency match outcomes. AB - PURPOSE: Studies have uniformly demonstrated misrepresentation of accomplishments by applicants to residency programs; yet it is unknown whether such applicants have a competitive advantage in the MATCH. Herein we identify the factors that influence an applicant's successful selection to a competitive residency. METHOD: Comparative study of 317 dermatology residency applicants during the 2007 application season. MAIN OUTCOME MEASURE: successful matching of an applicant into a U.S. dermatology residency. RESULTS: Factors positively associated with matching in univariate analysis included age (p=0.023); membership, Alpha Omega Alpha honors society (p=0.007); medical school research rank (p=0.013); USMLE scores (p<0.001); and number of unpublished manuscripts (p<0.001). Factors not associated with matching included the number of published manuscripts (p=0.460) and the combined impact factor of all published manuscripts (p=0.490). Multivariate analysis revealed that the USMLE Step 1 score (p=0.001), medical school research rank (p=0.040), and total number of unpublished manuscripts (p=0.046) were significantly associated matching in dermatology. Male gender trended towards but did not reach significance (p=0.054). CONCLUSIONS: Applicants that list multiple unpublished manuscripts have a significant competitive advantage in matching into a dermatology residency, even if these manuscripts remain unpublished. PMID- 22301039 TI - Hidradenitis suppurativa resulting in systemic amyloid A amyloidosis: a case report and review of the literature. AB - Hidradenitis suppurativa is a chronic, inflammatory disease of the follicular epithelium that presents as tender, subcutaneous nodules in an intertriginous distribution with sinus tract formation. Most commonly, hidradenitis suppurativa results in local complications, such as scarring and infection. However, systemic complications, such as anemia and arthropathies, have also been described. Herein, we report an unusual case of systemic amyloid A secondary to hidradenitis suppurativa. We describe a 39-year-old man with a long history of recurrent, tender, erythematous nodules in the axillary and anogenital regions, resulting in abscesses, sinus tract formation, and large areas of scarring. After 21 years of cutaneous disease with concurrent elevated systemic inflammatory markers, the patient was noted to have significant proteinuria. A kidney biopsy and immunostaining revealed deposits of amyloid A. Echocardiogram and electrocardiogram showed ventricular and atrial wall thickening with an appearance consistent with cardiac amyloid deposition. Systemic amyloid A amyloidosis is a serious, but rare, complication of chronic inflammatory disorders, including hidradenitis suppurativa, with potential multi-organ involvement including renal and cardiac manifestations. Amyloid A amyloidosis should be suspected in patients with chronic inflammatory cutaneous diseases who present with renal abnormalities, especially proteinuria or the nephrotic syndrome. PMID- 22301040 TI - Two distinct viral infections complicating pemphigus foliaceus. AB - We describe a patient with pemphigus foliaceus who developed two distinct disseminated cutaneous viral infections. Our patient is an 83-year-old female with a recent diagnosis of pemphigus foliaceus, who presented with painful ulcerations while on corticosteroids. Histopathology examination revealed disseminated herpes simplex virus (HSV). Despite adequate treatment with anti herpetic treatment, some ulcerations failed to heal. A second biopsy revealed the presence of cytomegalovirus (CMV). This was treated successfully with appropriate antiviral therapy. In patients with autoimmune bullous disease, the development of new skin pain or new constitutional symptoms, change in primary morphology, rapid disease progression, or failure to respond to appropriate therapies should prompt the clinician to consider a concurrent cutaneous viral infection. There should be a low threshold to perform ancillary tests, to re-biopsy, and in severe cases, to consider empiric treatment with antiviral treatment therapy and modification of immunosuppressive regimens. PMID- 22301041 TI - Actinomycetoma of the chest wall attributed to Nocardia nova after reconstructive surgery. AB - A 29-year-old man, presented with multiple ulcers, nodules, abscesses, fistulae, and atrophic scars, over the right chest wall. Six years prior, the patient had a car accident, which resulted in skin loss of the right arm, shoulder, thoracic wall. In addition, he suffered a supracondylar fracture; orthopedic surgery and skin grafts were required. Material discharging from sinus tracts was obtained for mycological and bacteriological studies. Direct microscopic examination revealed small white grains. Cultures on Sabouraud and Lowenstein-Jensen media isolated orange-white colonies suggestive of Nocardia. PCR assay identified Nocardia nova. Thoracic and right upper limb CT showed signs of chronic osteomyelitis. Treatment with imipenem/cilastatin for 8 weeks, followed by amoxicillin clavulanate for 6 months, resulted in healing of lesions and improvement in the patient's general health. Primary cutaneous nocardiosis remains a diagnostic challenge. Nocardia are soil-borne filamentous gram-positive bacteria. Identification of characteristic granules on examination of discharge smears from discharge or tissue biopsy is essential for diagnosing mycetoma. Because grain discharge is discontinuous, multiple clinical specimens should be submitted for microscopic examination and culture. Sulfonamides have been the mainstay of Nocardia actinomycetoma treatment. However, our patient's strain was resistant to Co-trimoxazole. Therefore, treatment with imipenem followed by amoxicillin clavulanate was favored, with good clinical and analytical response. PMID- 22301042 TI - Radiation port dermatophytosis: tinea corporis occurring at the site of irradiated skin. AB - Radiation port dermatophytosis is the occurrence of tinea corporis within the area of radiation therapy delivery. A 68-year-old man, while receiving proton beam radiation for adenocarcinoma of the prostate, developed a dermatophyte infection in the area of the radiotherapy port. Including this patient, 4 patients with radiation port dermatophytosis have been reported in the world literature. The epidemiology, clinical manifestations, histopathology, diagnosis, pathogenesis, and treatment of this condition are discussed. The diagnosis of radiation port dermatophytosis may be missed because it is misinterpreted as radiation-induced dermatitis. Thus, it is possible that radiation port dermatophytosis may be more prevalent in patients receiving radiation therapy. PMID- 22301043 TI - HIV photodermatitis presenting with widespread vitiligo-like depigmentation. AB - HIV photodermatitis encompasses a variety of clinical manifestations. We report a rare clinical presentation of HIV photodermatitis with widespread vitiligo-like depigmentation. PMID- 22301044 TI - Non-dermatophyte mold onychomycosis in Sri Lanka. AB - Dermatophytic and non-dermatophytic onychomycosis (NDM) was indistinguishable clinically in our case series. Making a clinical diagnosis of onychomycosis without mycology is the routine practice in Sri Lanka. The prevalence of NDM (45.8%) was very high in our patient population, followed by yeasts (34.1%); dermatophyte infection made up only 20%. Therefore, the treatment of onychomycosis with griseofulvin seems futile. Close contact with soil, the habit of walking barefoot, frequent emersion of hands in water, and a hot, humid climate partly explain the variation in causative pathogens in this case series. PMID- 22301045 TI - Langerhans cell histiocytosis: two clinical presentations in the same patient. AB - Langerhans cell histiocytosis (LCH) is a heterogeneous group of diseases characterized by a pathological proliferation of cells phenotypically similar to Langerhans cells. The disease course is variable, alternating between resolving and potentially fatal forms. The diagnosis is based on clinical appearance and confirmed by CD1a positivity and / or immunohistochemistry. We report the case of a male child of 3 months with two different presentations of Langerhans cell histiocytosis (LCH) at different times. The first presentation was classified as a self-healing LCH (formerly known as Hashimoto-Pritzker). The last presentation, although clinically suggestive of Letterer-Siwe (former designation), was not associated with systemic disease. This emphasizes that LCH cannot be compartmentalized into four groups, but considered a single disease with a wide spectrum of clinical presentations. This case underscores the importance of frequent and long-term follow-up of these patients. PMID- 22301046 TI - Epidermolysis bullosa simplex with mottled pigmentation. AB - Epidermolysis bullosa is a rare disorder with several variants. Included in this disorder is epidermolysis bullosa with mottled pigmentation (EBS-MP). We report a case of a young child with this rare disorder and explain the genetic cause. PMID- 22301047 TI - Multiple keratotic papules on palm. AB - Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is a rare nonhereditary malformation of the eccrine duct. A relationship with linear porokeratosis is not yet established; some consider it as a rare variant of porokeratosis involving the acrosyringium, whereas others consider it a separate entity based on distinctive clinical features and histologic accentuation within ostial structures. A 7-year-old girl presented with multiple asymptomatic keratotic papules over her right palm, present since the age of 6 months. These papules were arranged in a linear distribution over the palm and middle finger of the right hand. Most of the papules were discrete. However, lesions on the middle finger coalesced to form a plaque. Histology revealed a keratin filled deep invagination of the epidermis, notable for a column of parakeratosis ("cornoid lamella"). The dermis was notable for dilated eccrine ducts and absent inflammation. Considering the clinical and histological evidence, a diagnosis of PEODDN was made. Its clinical resemblance to linear lichen planus and linear porokeratosis is discussed. Also, we provide a brief review of this rare condition. PMID- 22301048 TI - Psoriasis and oral lesions: multicentric study of Oral Mucosa Diseases Italian Group (GIPMO). AB - OBJECTIVE: This is a multicentric, observational and controlled study designed to verify the existence of a significant association between plaque-type psoriasis and oral lesions, such as geographic tongue and/or fissured tongue. STUDY DESIGN: during a period of 9 months all consecutive patients with plaque-type psoriasis were enrolled using simple nonrandom (sequential) sampling. The control group included healthy subjects presenting to the same Dermatology centers to monitor pigmented skin lesions; the patients were matched for age and sex. All patients were examined for oral lesions. RESULTS: Out of a total of 535 psoriatic patients and 436 control group patients, oral mucosal lesions were detected in 188 (35.1%) and 86 (19.7%) cases, respectively, and the difference is statistically significant. Fissured tongue (FT) and geographic tongue (GT), which were most frequently detected, were seen more frequently in psoriatic patients (FT: 22.6%; GT: 9.1%) than the control group (FT: 10.3%; GT: 5.2%) (p<0.05). CONCLUSIONS: On the basis of the similar studies reported in the literature and the large number of patients involved in our study, we can conclude that FT and GT can be clearly suggested as oral manifestations of plaque-type psoriasis, although the reason for this association is not clear. PMID- 22301049 TI - Refractory pyoderma gangrenosum associated with ulcerative colitis successfully treated with infliximab. AB - Pyoderma gangrenosum (PG) is a rare, immune-mediated ulcerating skin disease. In up to 50 percent of the cases, PG is associated with underlying systemic disorders, most commonly inflammatory bowel diseases, connective tissue diseases, or hematological disorders. Herein, we present a case of refractory PG associated with ulcerative colitis (UC), successfully treated with infliximab. PMID- 22301050 TI - Another pitfall of sentinel lymph node biopsy: scar after lymph node biopsy 30 years ago revealed a sentinel lymph node. AB - In recent years, sentinel lymph node (SLN) biopsy has been used as a diagnostic and prognostic indicator for a number of tumors, including malignant melanoma. Sentinel lymph node biopsy using combined dye-radiotracer technique improved the detection rate and made the method easier. However, many pitfalls on the SLN procedure have been reported. Herein, we present a new pitfall. A formation of scar and lymph node tissue was detected as a SLN 30 years after lymph node biopsy. PMID- 22301051 TI - A case of idiopathic Mondor disease. AB - We report a case of very clinically prominent Mondor disease for which no precipitating etiology could be determined. PMID- 22301052 TI - Facial angiofibromas treated with topical rapamycin: an excellent choice with fast response. AB - Tuberous sclerosis (TS) is the second most common genodermatosis in our country and one of its main characteristics is the presence of facial angiofibromas. These benign tumors can be really bothersome for some patients and there is not a gold-standard treatment. Laser therapy has been used with good responses but it is a painful option and recurrence is guaranteed. TS develops as a result of a mutation of one of two genes, TSC1 or TSC2, which encode for hamartin and tuberin, respectively. TSC1 and TSC2 are tumor suppressors that inhibit mTOR, which if mutated results in mTOR activation, leading to an increase in protein translation. This eventually induces formation of hamartomatous tumors in patients with TSC. Oral rapamycin had been reported to be effective for the treatment of various tumors, apparently because of its action of inhibiting the m TOR complex. Recently it has been suggested that the drug may be effective when applied topically. We report the 6th case of facial AF treated with topical rapamycin, 1 percent, once per day. An excellent response was achieved surprisingly rapidly. We propose this option as a safe and effective therapy. PMID- 22301053 TI - Recent advances in oocyte and ovarian tissue cryopreservation and transplantation. AB - Options for preserving fertility in women include well-established methods such as fertility-sparing surgery, shielding to reduce radiation damage to reproductive organs, and emergency in-vitro fertilisation after controlled ovarian stimulation, with the aim of freezing embryos. The practice of transfering frozen or thawed embryos has been in place for over 25 years, and today is a routine clinical treatment in fertility clinics. Oocytes may also be frozen unfertilised for later thawing and fertilisation by intracytoplasmic sperm injection in vitro. In recent years, oocyte cryopreservation methods have further developed, reaching promising standards. More than 1000 children are born worldwide after fertilisation of frozen and thawed oocytes. Nevertheless, this technique is still considered experimental. In this chapter, we focus on options for fertility preservation still in development that can be offered to women. These include freezing of oocytes and ovarian cortex and the transplantation of ovarian tissue. PMID- 22301054 TI - Malignant ovarian germ-cell tumours. AB - Malignant ovarian germ-cell tumours account for about 5% of all ovarian malignancies and typically present in the teenage years. They are almost always unilateral and are exquisitely chemosensitive. As such, the surgical approach in young women with such tumours confined to a single ovary should aim to preserve fertility. In early disease, a unilateral salpingo-oophorectomy with careful surgical staging is of great importance in selecting appropriate adjuvant therapy. In advanced disease, the role of aggressive cytoreducation is not well defined, and removal of both ovaries does not confer improvement in outcome. Bleomycin, etoposide and cisplatin combination chemotherapy is regarded as the gold standard for adjuvant therapy. Studies evaluating ovarian and reproductive capacity after conservative surgery and chemotherapy for malignant ovarian germ cell tumours have consistently demonstrated excellent prognosis, with the return of normal menstrual function and fertility rates in these women with no increase in the risk of teratogenicity. PMID- 22301055 TI - Gynaecological cancer in pregnancy. AB - Cancer in pregnancy, fortunately, is uncommon. This is even more so for gynaecological cancer. Fertility preservation in gynaecological cancer is already a difficult issue, as the common gynaecological cancers affect organs intimately associated with conception and delivery. The presence of a viable pregnancy with gynaecological cancer presents tremendous challenges to the clinician, especially if the woman wants to conserve both her pregnancy and fertility. In this chapter, we address issues involved in such circumstances and suggest management decisions. PMID- 22301056 TI - Detailed examination of Mg2+ and pH sensitivity of human TRPM7 channels. AB - TRPM7 channel kinase is a protein highly expressed in cells of hematopoietic lineage, such as lymphocytes. Studies performed in native and heterologous expression systems have shown that TRPM7 forms nonselective cation channels functional in the plasma membrane and activated on depletion of cellular Mg(2+). In addition to internal Mg(2+), cytosolic pH and the phospholipid phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P(2)] are potent physiological regulators of this channel: protons inhibit, while PI(4,5)P(2) is required for TRPM7 channel activity. These channels are also inhibited from inside by other metal cations and polyamines. While the regulation of TRPM7 channels by internal metal ions, acidic pH, and PI(4,5)P(2) is voltage independent, extracellular metal cations and polyamines block voltage dependently at micromolar concentrations and appear to occupy a distinct blocking site. In the present study we investigated intracellular Mg(2+) and pH dependence of native TRPM7 currents using whole cell patch-clamp electrophysiology in human Jurkat T lymphocytes and HEK293 cells. Our main findings are 1) Mg(2+) inhibition involves not one but two separate sites of high (~10 MUM) and low (~165 MUM) affinity; and 2) while sharing certain characteristics with Mg(2+) inhibition, protons most likely inhibit through one inhibitory site, corresponding to the low-affinity Mg(2+) site, with an estimated IC(50) of pH 6.3. Additionally, we present data on amplitude distribution of preactivated TRPM7 currents in Jurkat T lymphocytes in the absence of prior Mg(2+) or proton depletion. PMID- 22301057 TI - Abl regulates smooth muscle cell proliferation by modulating actin dynamics and ERK1/2 activation. AB - Abl is a nonreceptor tyrosine kinase that has a role in regulating migration and adhesion of nonmuscle cells as well as smooth muscle contraction. The role of Abl in smooth muscle cell proliferation has not been investigated. In this study, treatment with endothelin-1 (ET-1) and platelet-derived growth factor (PDGF) increased Abl phosphorylation at Tyr(412) (an indication of Abl activation) in vascular smooth muscle cells. To assess the role of Abl in smooth muscle cell proliferation, we generated stable Abl knockdown cells by using lentivirus mediated RNA interference. ET-1- and PDGF-induced cell proliferation was attenuated in Abl knockdown cells compared with cells expressing control shRNA and uninfected cells. Abl silencing also arrested cell cycle progression from G(0)/G(1) to S phase. Furthermore, activation of smooth muscle cells with ET-1 and PDGF induced phosphorylation of ERK1/2 and Akt. Abl knockdown attenuated ERK1/2 phosphorylation in smooth muscle cells stimulated with ET-1 and PDGF. However, Akt phosphorylation upon stimulation with ET-1 and PDGF was not reduced. Because Abl is known to regulate actin polymerization in smooth muscle, we also evaluated the effects of inhibition of actin polymerization on phosphorylation of ERK1/2. Pretreatment with the actin polymerization inhibitor latrunculin-A also blocked ERK1/2 phosphorylation during activation with ET-1 and PDGF. The results suggest that Abl may regulate smooth muscle cell proliferation by modulating actin dynamics and ERK1/2 phosphorylation during mitogenic activation. PMID- 22301058 TI - Molecular assembly and dynamics of fluorescent protein-tagged single KCa1.1 channel in expression system and vascular smooth muscle cells. AB - The large-conductance Ca(2+)-activated K(+) (K(Ca)1.1, BK) channel has pivotal roles in the regulation of vascular tone. To clarify the molecular dynamics of BK channels and their functionally coupled protein on the membrane surface, we examined single-molecule imaging of fluorescent-labeled BK subunits in the plasma membrane using total internal reflection fluorescence (TIRF) microscopy. The dynamic mobility of yellow fluorescent protein (YFP)-tagged BKalpha subunit (BKalpha-YFP) expressed in human embryo kidney 293 (HEK) cells was detected in TIRF regions at the level of individual channels and their clusters on the plasma membrane with a diffusion coefficient of 6.7 * 10(3) nm(2)/s. When BKalpha-YFP was coexpressed with cyan fluorescent protein (CFP)-tagged BKbeta1 subunit (BKbeta1-CFP) in HEK cells, the mobility was reduced by ~50%. Fluorescent image analyses suggest that green fluorescent protein (GFP)-tagged BKalpha subunit (BKalpha-GFP) expressed in vascular smooth muscle cells (VSMCs), at low density, preferentially formed a heterotetrameric molecular assembly with native BKalpha subunits, rather than homotetrameric BKalpha-GFP. Movement of BKalpha-YFP in VSMCs (0.29 * 10(3) nm(2)/s) was far more restricted than BKalpha-YFP/BKbeta1-CFP in HEK cells (2.5 * 10(3) nm(2)/s). Actin disruption by pretreatment with cytochalasin D in VSMCs appeared to increase the mobile behavior of BKalpha-YFP, which was then significantly reduced by addition of jasplakinolide. Most BKalpha YFP colocalized with caveolin 1 (Cav1)-CFP in VSMCs, but unexpectedly not frequently in HEK cells. Fluorescence resonance energy transfer analyses showed the direct interaction between BKalpha-YFP and Cav1-CFP, particularly in VSMCs. These results, obtained by single molecule imaging in living cells, indicate that the dynamics of BKalpha molecules on the membrane surface are strongly restricted or regulated by its auxiliary beta-subunit, cytoskeleton, and direct interaction with Cav1 in VSMCs. PMID- 22301059 TI - Mouse SGLT3a generates proton-activated currents but does not transport sugar. AB - Sodium-glucose cotransporters (SGLTs) are secondary active transporters belonging to the SLC5 gene family. SGLT1, a well-characterized member of this family, electrogenically transports glucose and galactose. Human SGLT3 (hSGLT3), despite sharing a high amino acid identity with human SGLT1 (hSGLT1), does not transport sugar, although functions as a sugar sensor. In contrast to humans, two different genes in mice and rats code for two different SGLT3 proteins, SGLT3a and SGLT3b. We previously cloned and characterized mouse SGLT3b (mSGLT3b) and showed that, while it does transport sugar like SGLT1, it likely functions as a physiological sugar sensor like hSGLT3. In this study, we cloned mouse SGLT3a (mSGLT3a) and characterized it by expressing it in Xenopus laevis oocytes and performing electrophysiology and sugar transport assays. mSGLT3a did not transport sugar, and sugars did not induce currents at pH 7.4, though acidic pH induced inward currents that increased in the presence of sugar. Moreover, mutation of residue 457 from glutamate to glutamine resulted in a Na(+)-dependent transport of sugar that was inhibited by phlorizin. To corroborate our results in oocytes, we expressed and characterized mSGLT3a in mammalian cells and confirmed our findings. In addition, we cloned, expressed, and characterized rat SGLT3a in oocytes and found characteristics similar to mSGLT3a. In summary, acidic pH induces currents in mSGLT3a, and sugar-induced currents are increased at acidic pH, but wild-type SGLT3a does not transport sugar. PMID- 22301060 TI - Increased Na+/H+ exchanger activity on the apical surface of a cilium-deficient cortical collecting duct principal cell model of polycystic kidney disease. AB - Pathophysiological anomalies in autosomal dominant and recessive forms of polycystic kidney disease (PKD) may derive from impaired function/formation of the apical central monocilium of ductal epithelia such as that seen in the Oak Ridge polycystic kidney or orpk (Ift88(Tg737Rpw)) mouse and its immortalized cell models for the renal collecting duct. According to a previous study, Na/H exchanger (NHE) activity may contribute to hyperabsorptive Na(+) movement in cilium-deficient ("mutant") cortical collecting duct principal cell monolayers derived from the orpk mice compared with cilium-competent ("rescued") monolayers. To examine NHE activity, we measured intracellular pH (pH(i)) by fluorescence imaging with the pH-sensitive dye BCECF, and used a custom-designed perfusion chamber to control the apical and basolateral solutions independently. Both mutant and rescued monolayers exhibited basolateral Na(+)-dependent acid-base transporter activity in the nominal absence of CO(2)/HCO(3)(-). However, only the mutant cells displayed appreciable apical Na(+)-induced pH(i) recoveries from NH(4)(+) prepulse-induced acid loads. Similar results were obtained with isolated, perfused collecting ducts from orpk vs. wild-type mice. The pH(i) dependence of basolateral cariporide/HOE-694-sensitive NHE activity under our experimental conditions was similar in both mutant and rescued cells, and 3.5- to 4.5-fold greater than apical HOE-sensitive NHE activity in the mutant cells (pH(i) 6.23-6.68). Increased apical NHE activity correlated with increased apical NHE1 expression in the mutant cells, and increased apical localization in collecting ducts of kidney sections from orpk vs. control mice. A kidney-specific conditional cilium-knockout mouse produced a more acidic urine compared with wild type littermates and became alkalotic by 28 days of age. This study provides the first description of altered NHE activity, and an associated acid-base anomaly in any form of PKD. PMID- 22301061 TI - [From bench to bedside: experience of the glioblastoma model for the optimization of radiosensitization]. AB - Despite significant progress in the treatment of glioblastoma, the prognosis of these radioresistant, invasive and hypoxic tumours remain dark. The constant relapse after treatment of this tumour is in part due to its intra-cellular but also micro-environmental radioresistance, largely controlled by growth factors and their receptors. The complexity of the biology of these tumours and the presence of numerous cross-talks between the pathways of these different growth factors can be in part responsible for the negative results obtained in clinical trials associating radiotherapy and targeted drugs designed without previous in vitro and in vivo studies validating the proof of concept of a specific target as key factor of radioresistance. In the aim to optimize the treatment of glioblastoma and to reduce the risks of failure of new trials, several laboratories and clinical departments are developing translational research in radiotherapy and radiobiology, validating in vitro and then in orthotopic xenografts interesting targets, then studying the radiosensitizing effect of targeted drugs directed against these proteins, studying the mechanisms of action and resistance of these drugs, validating these proteins as predictive factors of response to radiotherapy in the patients, and then designing clinical trials, integrating metabolic or functional imaging and surrogate markers to better understand the mechanism of action of these associations. We describe in this article the main translational research axis developed for radiosensitizing glioblastoma, which our lab and department have pursued for several years. PMID- 22301062 TI - Development of a novel coding scheme (SABICS) to record nurse-child interactive behaviours in a community dental preventive intervention. AB - OBJECTIVE: To develop and validate the St Andrews Behavioural Interaction Coding Scheme (SABICS): a tool to record nurse-child interactive behaviours. METHODS: The SABICS was developed primarily from observation of video recorded interactions; and refined through an iterative process of applying the scheme to new data sets. Its practical applicability was assessed via implementation of the scheme on specialised behavioural coding software. Reliability was calculated using Cohen's Kappa. Discriminant validity was assessed using logistic regression. RESULTS: The SABICS contains 48 codes. Fifty-five nurse-child interactions were successfully coded through administering the scheme on The Observer XT8.0 system. Two visualization results of interaction patterns demonstrated the scheme's capability of capturing complex interaction processes. Cohen's Kappa was 0.66 (inter-coder) and 0.88 and 0.78 (two intra-coders). The frequency of nurse behaviours, such as "instruction" (OR = 1.32, p = 0.027) and "praise" (OR = 2.04, p = 0.027), predicted a child receiving the intervention. CONCLUSIONS: The SABICS is a unique system to record interactions between dental nurses and 3-5 years old children. It records and displays complex nurse-child interactive behaviours. It is easily administered and demonstrates reasonable psychometric properties. PRACTICE IMPLICATIONS: The SABICS has potential for other paediatric settings. Its development procedure may be helpful for other similar coding scheme development. PMID- 22301063 TI - Ten-year relative survival and causes of death in elderly patients treated with R CHOP or CHOP in the GELA LNH-985 trial. PMID- 22301064 TI - Dexmedetomidine prevents remifentanil-induced postoperative hyperalgesia and decreases spinal tyrosine phosphorylation of N-methyl-d-aspartate receptor 2B subunit. AB - Numerous studies have demonstrated that prolonged opioid exposure can enhance pain sensitivity that presents as opioid-induced hyperalgesia (OIH). Activation of spinal alpha2-adrenergic receptor may play an important role in the development of OIH. Dexmedetomidine is an alpha2-adrenergic agonist that has been shown to synergize with opioids. The aim of this study was to investigate the antihyperalgesia effects of dexmedetomidine on remifentanil-induced postinfusion hyperalgesia in a rat model of incision pain. We also evaluated whether the antihyperalgesic effects of dexmedetomidine were associated with suppression of NMDAR excitability, as measured by a reduction in spinal cord NR2B phosphorylation. Dexmedetomidine (12.5 MUg/kg, 25 MUg/kg, 50 MUg/kg) was administered subcutaneously 30 min before plantar incision. Pretreatment with dexmedetomidine significantly decreased remifentanil-induced hyperalgesia, as indicated by increased paw withdrawal latencies and thresholds to thermal and mechanical stimulation respectively. Correlated with the pain behavior changes, Western blotting experiments also revealed that dexmedetomidine could decrease NR2B subunit phosphorylation (Tyr1472 site) in the dorsal horn, which was upregulated after remifentanil infusion. These results suggest that dexmedetomidine can efficiently alleviate OIH and it may be an effective novel option for the treatment of OIH. Our data also provide evidence that dexmedetomidine's anti-hyperalgesic effect may depend on its ability to modulate spinal cord NMDAR activation via suppression of NR2B phosphorylation. PMID- 22301065 TI - Differences and discrepancies between 2005 and 2008 Abbreviated Injury Scale versions - time to standardise. AB - The aim of this letter is to facilitate the standardisation of Abbreviated Injury Scale (AIS) codesets used to code injuries in trauma registries. We have compiled a definitive list of the changes which have been implemented between the AIS 2005 and Update 2008 versions. While the AIS 2008 codeset appears to have remained consistent since its release, we have identified discrepancies between the codesets in copies of AIS 2005 dictionaries. As a result, we recommend that use of the AIS 2005 should be discontinued in favour of the Update 2008 version. PMID- 22301066 TI - Ranibizumab for macular edema due to retinal vein occlusions: long-term follow-up in the HORIZON trial. AB - PURPOSE: To assess long-term safety and efficacy of intraocular ranibizumab injections in patients with macular edema after retinal vein occlusion (RVO). DESIGN: Open-label extension trial of the 12-month Ranibizumab for the Treatment of Macular Edema following Branch Retinal Vein Occlusion: Evaluation of Efficacy and Safety (BRAVO) and Central Retinal Vein Occlusion Study: Evaluation of Efficacy and Safety (CRUISE) trials. PARTICIPANTS: We included 304 patients who completed BRAVO and 304 patients who completed CRUISE. METHODS: Patients were seen at least every 3 months and given an intraocular injection of 0.5 mg ranibizumab if they met prespecified retreatment criteria. MAIN OUTCOME MEASURES: Primary outcomes were incidence and severity of ocular and nonocular adverse events (AEs). Key efficacy outcomes included mean change from baseline best corrected visual acuity (BCVA) letter score by Early Treatment Diabetic Retinopathy Study protocol and central foveal thickness. RESULTS: In patients who completed month 12, the mean number of injections (excluding month 12 injection) in the sham/0.5-, 0.3/0.5-, and 0.5-mg groups was 2.0, 2.4, and 2.1 (branch RVO) and 2.9, 3.8, and 3.5 (central RVO), respectively. The incidence of study eye ocular serious AEs (SAEs) and SAEs potentially related to systemic vascular endothelial growth factor inhibition across treatment arms was 2% to 9% and 1% to 6%, respectively. The mean change from baseline BCVA letter score at month 12 in branch RVO patients was 0.9 (sham/0.5 mg), -2.3 (0.3/0.5 mg), and -0.7 (0.5 mg), respectively. The mean change from baseline BCVA at month 12 in central RVO patients was -4.2 (sham/0.5 mg), -5.2 (0.3/0.5 mg), and -4.1 (0.5 mg), respectively. CONCLUSIONS: No new safety events were identified with long-term use of ranibizumab; rates of SAEs potentially related to treatment were consistent with prior ranibizumab trials. Reduced follow-up and fewer ranibizumab injections in the second year of treatment were associated with a decline in vision in central RVO patients, but vision in branch RVO patients remained stable. Results suggest that during the second year of ranibizumab treatment of RVO patients, follow-up and injections should be individualized and, on average, central RVO patients may require more frequent follow-up than every 3 months. PMID- 22301067 TI - Molecular characterisation of porcine miR-155 and its regulatory roles in the TLR3/TLR4 pathways. AB - MiR-155 plays very important roles in host inflammation and immunity. However, few studies have focused on miR-155 in livestock. In this study, the molecular characterisation of miR-155 and its functional roles in TLR3/TLR4 signalling pathways were investigated in pigs. The results indicated that miR-155 was highly expressed in the spleen and fat tissues of the pig. In PK-15 cells, miR-155 was up-regulated 4h after LPS stimulation and up-regulated 12h and 24h after poly (I:C) stimulation. Furthermore, the overexpression of miR-155 significantly activated the TLR3/TLR4 signalling pathways, and the inhibition of miR-155 suppressed these pathways. Thus, miR-155 played positive regulatory roles in TLR3/TLR4 signalling pathways. Additionally, one T/C SNP of miR-155 was significantly associated with basophil percentage (BA%), absolute eosinophili value (EO) and the distribution width of the least squares mean of CD3-CD4-CD8+ T cells (DWT) in pigs. Our study offers new evidence on the immune function of miR 155 in pigs. PMID- 22301068 TI - Intubated patients developing tracheobronchitis or pneumonia have distinctive complement system gene expression signatures in the pre-infection period: a pilot study. AB - INTRODUCTION: It remains unknown why some intubated patients remain infection free while others develop tracheobronchitis (VAT) or pneumonia (VAP). OBJECTIVE: To identify and compare VAP/VAT gene expression "signatures" using genome-wide oligonucleotide microarrays. MATERIAL AND METHODS: A prospective translational study of gene expression profiles of VAP and VAT groups was carried out, establishing comparisons in both pre-infection and infection phases. Pathway and functional analyses were performed with Ingenuity Pathway Analysis (IPA). Data analysis and hierarchical clustering of the genes involved in the signalling pathways expressed differentially in the two groups were performed with GeneSpring GX 11.0. RESULTS: Eight patients developing respiratory infections (3 VAP and 5 VAT) after 4 days of mechanical ventilation were assessed. Comparison of gene expression profiles in the pre-infection period revealed 5595 genes expressed differentially between VAP and VAT (p<0.01, fold change >2). Comparative IPA analysis identified a significant depression of the complement system signalling pathway in the VAP group, affecting the classical pathway along with the final common pathway (p<0.05). In addition, the cAMP and calcium signalling pathways were also significantly depressed in the VAP group during the pre-infection phase also. CONCLUSION: Intubated patients complicated with pneumonia developed immune impairment in the pre-infection period, manifesting as a relatively lower expression of genes involved in the complement system that differed from patients developing tracheobronchitis. These findings suggest that a significant proportion of VAP episodes cannot be prevented, but might be treatable through pre-emptive therapy. PMID- 22301069 TI - Assessment of genotoxicity of herbal medicinal products: a co-ordinated approach. AB - The submission of data on genotoxicity is a precondition for marketing authorisation respectively registration of herbal medicinal products (HMPs) with well established or traditional use in some countries. In European regulatory guidelines prepared by the Committee on Herbal Medicinal Products (HMPC) of the European drug regulatory agency EMA, a test strategy is defined giving a pragmatic framework adapted to the assessment of the potential genotoxicity of HMPs. It describes a stepwise approach, including the possibility to reduce the number of extracts of a herbal drug to be tested by the use of a bracketing and matrixing approach. According to this strategy, Kooperation Phytopharmaka, a scientific society in the field of HMPs, has so far coordinated the conduction of genotoxicity tests for 30 herbal drugs within the frame of a joint project of several manufacturers of HMPs. Results are delivered to the cooperation partners for use in regulatory applications. PMID- 22301070 TI - Medicinal chemistry matters - a call for discipline in our discipline. AB - Medicinal chemistry makes a vital contribution to small molecule drug discovery, and the quality of it contributes directly to research effectiveness as well as to downstream costs, speed and survival in development. In recent years, the discipline of medicinal chemistry has evolved and witnessed many noteworthy contributions that propose and offer potential improvements to medicinal chemistry practice; however, the impact of these ideas is limited by their acceptance and deployment into every-day activity and, as a result, the quality of medicinal chemistry remains variable. For the good of the industry and the medicinal chemistry discipline, there is a need to move from retrospective learning to prospective control of medicinal chemistry practice to improve cost effectiveness, probability of success and survival rates. PMID- 22301071 TI - If you want to shoot for the moon, you gotta have the right stuff. PMID- 22301072 TI - Effect of abacavir on acute changes in biomarkers associated with cardiovascular dysfunction. AB - BACKGROUND: This study examined the effect of abacavir on acute changes in biomarkers associated with cardiovascular dysfunction. METHODS: Among the Study to Understand the Natural History of HIV/AIDS in the Era of Effective therapy (SUN) participants, we identified 25 individuals (cases) who were HLA-B5701 negative and who had >= 2 weeks without abacavir exposure at one visit and >= 2 weeks with abacavir exposure at the consecutive visit while maintaining viral suppression. We identified 43 individuals (controls) similarly unexposed and exposed to tenofovir. We assessed concentrations of prothrombin fragment F(1+2), D-dimer, high-sensitivity C-reactive protein, interleukin-8, intercellular adhesion molecule-1, vascular adhesion molecule-1, E-selectin, P-selectin, serum amyloid A and serum amyloid P. We examined the median percentage change of these biomarkers from the unexposed to exposed state among cases and controls compared with the expected assay variability using a sign test, and compared changes among cases with controls using the Wilcoxon rank-sum test. RESULTS: Baseline characteristics were similar between cases and controls: median age 45 versus 46 years, 80% versus 81% male, 64% versus 63% non-Hispanic White and median CD4(+) T cell count 538 versus 601 cells/mm(3), respectively. Mean exposure times were 65 and 15 weeks for abacavir and tenofovir, respectively. We observed no significant changes in biomarkers from the unexposed to exposed state among cases or controls compared with the expected assay variability. We found that no biomarkers were significantly increased among cases compared with controls; however, prothrombin fragment F(1+2) was significantly lower among controls (P=0.035). CONCLUSIONS: In virologically suppressed contemporary HIV-infected patients, abacavir exposure was not associated with increases in biomarkers associated with increased cardiovascular risk. PMID- 22301073 TI - Is there any advantage to three-dimensional planning for vaginal cuff brachytherapy? AB - PURPOSE: To evaluate whether the three-dimensional (3D) CT-based high-dose rate planning for vaginal cuff brachytherapy offers any advantage over the 2D orthogonal film-based library plans for adjuvant treatment of endometrial cancers. METHODS AND MATERIALS: Eighty-four consecutive postoperative patients with endometrial cancers treated with vaginal brachytherapy as an adjuvant treatment were analyzed. Patients had CT imaging-based plans. Clinical target volume (CTV) was defined by expanding the upper 2.5cm of the cylinder by 5mm in all directions and editing to exclude any bladder and rectum. The dose prescribed was 7Gy with three fractions at 5mm depth with a goal of D(90) >=100% for CTV. All dosimetric parameters were compared with library-based plans. RESULTS: Both the 2D- and 3D-based plans allowed sufficient dosage to the CTV (D(90) for CTV >=95%). The doses of 0.1, 1, and 2cc to rectum and bladder were significantly higher for 2D-based plans (p<=0.001 in each parameter). D(2 cc) with 2D plan for rectum and bladder was >100% (range: 103-116%) in 7 (8%) and 6 (7%) patients, respectively. In contrast, no patients had D(2 cc) >100% with 3D planning for both organs. CONCLUSION: Three-dimensional CT-based planning for high-dose rate vaginal cuff brachytherapy helps to decrease dose to critical organs without compromising coverage of CTV by customizing the dosimetry according to individual patient anatomy. PMID- 22301074 TI - Manual GO annotation of predictive protein signatures: the InterPro approach to GO curation. AB - InterPro amalgamates predictive protein signatures from a number of well-known partner databases into a single resource. To aid with interpretation of results, InterPro entries are manually annotated with terms from the Gene Ontology (GO). The InterPro2GO mappings are comprised of the cross-references between these two resources and are the largest source of GO annotation predictions for proteins. Here, we describe the protocol by which InterPro curators integrate GO terms into the InterPro database. We discuss the unique challenges involved in integrating specific GO terms with entries that may describe a diverse set of proteins, and we illustrate, with examples, how InterPro hierarchies reflect GO terms of increasing specificity. We describe a revised protocol for GO mapping that enables us to assign GO terms to domains based on the function of the individual domain, rather than the function of the families in which the domain is found. We also discuss how taxonomic constraints are dealt with and those cases where we are unable to add any appropriate GO terms. Expert manual annotation of InterPro entries with GO terms enables users to infer function, process or subcellular information for uncharacterized sequences based on sequence matches to predictive models. Database URL: http://www.ebi.ac.uk/interpro. The complete InterPro2GO mappings are available at: ftp://ftp.ebi.ac.uk/pub/databases/GO/goa/external2go/interpro2go. PMID- 22301075 TI - Nitazoxanide for the empiric treatment of pediatric infectious diarrhea. AB - We conducted a double-blind, placebo-controlled clinical trial to demonstrate the efficacy of nitazoxanide suspension for the treatment of presumed infectious diarrhea in children. Eligible patients must have had diarrheal illness lasting 3 29 days. Patients were randomized to receive either nitazoxanide or placebo twice daily for three days. The primary endpoint was time from first dose to resolution of symptoms. One hundred children mean age 3.3 years were enrolled. The median time to resolution of symptoms for nitazoxanide treated patients was 23 hours (IQR 4-48 hours) vs 103.5 hours (IQR 63->168 hours) for placebo (p<0.001). An analysis by disease subset indicated nitazoxanide treated patients had statistically shorter durations of diarrheal illness associated with Giardia lamblia (n=32, p<0.001) and those with no identified enteropathogen (n=38, p=0.008), when compared to placebo. The study medication was well tolerated. Overall, nitazoxanide was effective at reducing the duration of diarrheal illness associated with multiple etiologies, including patients with no identified enteropathogen. These results suggest nitazoxanide may be a viable therapeutic option for the empiric treatment of diarrheal illness in children where the etiology is unknown or presumed to be of infectious origin. Clinical trial registry number NCT01326338. PMID- 22301076 TI - Clinical features and epidemiology of cutaneous leishmaniasis and Leishmania major/HIV co-infection in Cameroon: results of a large cross-sectional study. AB - Cutaneous leishmaniasis (CL) is endemic in Central Africa, including Cameroon. However, data on its prevalence and co-infection with HIV are scarce. Here we present the results of a large cross-sectional study reporting the prevalence, clinical features and species identification of CL and HIV co-infection in northern Cameroon. A total of 32 466 subjects were clinically screened for CL during a door-to-door survey, followed by parasitological diagnosis in the field laboratory. Amongst the subjects surveyed, 146 (0.4%) were diagnosed with active CL. Seven (4.8%) of these 146 CL patients tested positive for HIV-1 and/or HIV-2. The number of lesions per CL patient ranged from 1 to 20. Three of the five subjects with >10 active lesions were co-infected with HIV. In both CL and HIV co infected subjects, three successful parasite isolates were identified as Leishmania major by PCR. This first report of L. major/HIV co-infection in Cameroon and Central Africa confirms the endemicity of CL in the region and highlights a worsened CL pathology in HIV co-infected individuals. These findings provide important data necessary for the development and implementation of successful control programmes against CL and HIV in this geographical area. PMID- 22301077 TI - Depressive symptoms, antidepressant use, and future cognitive health in postmenopausal women: the Women's Health Initiative Memory Study. AB - BACKGROUND: Antidepressants are commonly prescribed medications in the elderly, but their relationship with incident mild cognitive impairment (MCI) and probable dementia is unknown. METHODS: The study cohort included 6,998 cognitively healthy, postmenopausal women, aged 65-79 years, who were enrolled in a hormone therapy clinical trial and had baseline depressive symptoms and antidepressant use history assessments at enrollment, and at least one postbaseline cognitive measurement. Participants were followed annually and the follow-up averaged 7.5 years for MCI and probable dementia outcomes. A central adjudication committee classified the presence of MCI and probable dementia based on extensive neuropsychiatric examination. RESULTS: Three hundred and eighty-three (5%) women were on antidepressants at baseline. Antidepressant use was associated with a 70% increased risk of MCI, after controlling for potential covariates including the degree of depressive symptom severity. Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) were both associated with MCI (SSRIs: hazard ratios (HR), 1.78 [95% CI, 1.01-3.13]; TCAs: HR, 1.78 [95% CI, 0.99-3.21]). Depressed users (HR, 2.44 [95% CI, 1.24-4.80]), non-depressed users (HR, 1.79 [95% CI, 1.13-2.85]), and depressed non-users (HR, 1.62 [95% CI, 1.13 2.32]) had increased risk of incident MCI. Similarly, all three groups had increased risk of either MCI or dementia, relative to the control cohort. CONCLUSIONS: Antidepressant use and different levels of depression severity were associated with subsequent cognitive impairment in a large cohort of postmenopausal women. Future research should examine the role of antidepressants in the depression-dementia relationship and determine if antidepressants can prevent incident MCI and dementia in individuals with late-life depression subtypes with different levels of severity. PMID- 22301078 TI - CFD analysis of dense gas dispersion in indoor environment for risk assessment and risk mitigation. AB - Environmental risks are inherent in the operation of any complex chemical process industry. The indoor release of hazardous chemicals that are denser than air is a topic of special concern, since dense clouds tend to persist at ground level or human breath level which leads to a magnification of their harmful potential. In the present work, we propose a computational fluid dynamics (CFD) based model for indoor risk assessment considering accidental release of a sustained, small, undetected leak of a dense toxic gas (chlorine) in an industrial indoor environment. Results from simulations show that the denser chlorine gas spreads like a liquid and flows all along the floor. At the same time, its concentration at a point away from the ground level increases slowly, thus showing that both stratification and dilution effects are present as the dense gas spreads. The implications of this spreading pattern from a risk assessment and risk mitigation point of view are discussed. PMID- 22301079 TI - Biodegradation of ethylene dibromide (1,2-dibromoethane [EDB]) in microcosms simulating in situ and biostimulated conditions. AB - Although 1,2-dibromoethane (EDB) is a common groundwater contaminant, there is the lack of knowledge surrounding EDB biodegradation, especially under aerobic conditions. We have performed an extensive microcosm study to investigate the biodegradation of EDB under simulated in situ and biostimulated conditions. The materials for soil microcosms were collected from an EDB-contaminated aquifer at the Massachusetts Military Reservation in Cape Cod, MA. This EDB plume has persisted for nearly 40 years in both aerobic and anaerobic EDB zones of the aquifer. Microcosms were constructed under environmentally relevant conditions (field EDB and DO concentrations; incubated at 12 degrees C). The results showed that natural attenuation occurred under anaerobic conditions but not under aerobic conditions, explaining why aerobic EDB contamination is so persistent. EDB degradation rates were greater under biostimulated conditions for both the aerobic and anaerobic microcosms. Particularly for aerobic biostimulation, methane-amended microcosms degraded EDB, on average, at a first order rate eight times faster than unamended microcosms. The best performing replicate achieved an EDB degradation rate of 7.0 yr(-1) (half-life (t(1/2))=0.10 yr). Residual methane concentrations and the emergence of methanotrophic bacteria, measured by culture independent bacterial analysis, provided strong indications that EDB degradation in aerobic methane-amended microcosms occurred via cometabolic degradation. These results indicate the potential for enhanced natural attenuation of EDB and that methane could be considered co-substrate for EDB bioremediation for the EDB contaminated groundwater in aerobic zone. PMID- 22301080 TI - Effect of silicon on reducing cadmium toxicity in durum wheat (Triticum turgidum L. cv. Claudio W.) grown in a soil with aged contamination. AB - Agricultural soil contamination and subsequently crops still require alternative solutions to reduce associated environmental risks. The effects of silica application on alleviating cadmium (Cd) phytotoxicity in wheat plants were investigated in a 71-day pot experiment conducted with a historically contaminated agricultural soil. We used amorphous silica (ASi) that had been extracted from a diatomite mine for Si distribution at 0, 1, 10 and 15 ton ASi ha(-1). ASi applications increased plant biomass and plant Si concentrations, reduced the available Cd in the soil and the Cd translocation to shoots, while Cd was more efficiently sequestrated in roots. But ASi is limiting for Si uptake by plants. We conclude that significant plant-available Si in soil contributes to decreased Cd concentrations in wheat shoots and could be implemented in a general scheme aiming at controlling Cd concentrations in wheat. PMID- 22301081 TI - Problem recognition, intention to stop use, and treatment use among regular heroin injectors. AB - This study investigated frequency of recent use as an explanatory variable in problem recognition and intention to stop use among regular injection heroin users. Data from the NEURO-HIV Epidemiologic Study, an investigation of neuropsychological and social-behavioral risk factors for HIV and hepatitis A, B, and C among injection and noninjection drug users, were used in the analyses. Participants (N = 337) consisted of those who reported injecting heroin daily or nearly daily for a period of 3 months. Multiple linear regression analysis revealed that frequency of recent injection drug use predicted problem recognition (beta = .17), but not intention to stop use; although marginal, being female (beta = .15), and homeless (beta = .14) contributed to intention to stop use. Past 6-month treatment participation was 48%, and current treatment enrollment was 26% among study participants. This study highlights the importance of capitalizing on injection drug users' recent use as a mechanism for treatment interventions. PMID- 22301082 TI - Developing an evidence-based, multimedia group counseling curriculum toolkit. AB - Training community-based addiction counselors in empirically supported treatments (ESTs) far exceeds the ever-decreasing resources of publicly funded treatment agencies. This feasibility study describes the development and pilot testing of a group counseling toolkit (an approach adapted from the education field) focused on relapse prevention (RP). When counselors (N = 17) used the RP toolkit after 3 hours of training, their content adherence scores on "coping with craving" and "drug refusal skills" showed significant improvement, as indicated by very large effect sizes (Cohen's d = 1.49 and 1.34, respectively). Counselor skillfulness, in the "adequate-to-average" range at baseline, did not change. Although this feasibility study indicates some benefit to counselor EST acquisition, it is important to note that the impact of the curriculum on client outcomes is unknown. Because a majority of addiction treatment is delivered in group format, a multimedia curriculum approach may assist counselors in applying ESTs in the context of actual service delivery. PMID- 22301083 TI - Physicians in the substance abuse treatment workforce: understanding their employment within publicly funded treatment organizations. AB - The employment of physicians by substance abuse treatment organizations is understudied, despite physicians' importance in implementing pharmacotherapy and integrating treatment into the broader system of medical care. Drawing on data collected from 249 publicly funded treatment organizations, this study examined organizational and environmental factors associated with the employment of physicians in these settings. A negative binomial regression model indicated that greater numbers of physicians were employed when organizations offered detoxification services, were embedded in health care settings, and were larger in size. Funding barriers, including the costs of physicians and inadequate reimbursement by funders, were negatively associated with physician employment. Programs unaware that they could use state contract funding to pay for medical staff employed fewer numbers of physicians than programs aware of this type of state policy. Attempts to increase physician employment in substance abuse treatment may require attention to both organizational and environmental factors rather than simply trying to attract individuals to the field. Increasing physician employment may be challenging in the current economic climate. PMID- 22301084 TI - Comparing buprenorphine induction experience with heroin and prescription opioid users. AB - Prescription opioid (PO)-dependent treatment presentations are becoming increasingly common; however, most research on the treatment of opioid-dependent populations has been conducted in heroin users. The aim of this secondary data analysis was to compare the buprenorphine induction experience of 167 heroin and 61 PO users. Results demonstrate that although the groups differed on some baseline characteristics, many of the key induction experience variables were comparable between the groups. Heroin users were found to have significantly higher preinduction Clinical Opiate Withdrawal Scale (COWS) scores (p = .014) and postinduction COWS score (p = .008) compared with the PO users. No differences between groups were found for self-reported craving and withdrawal scores, mean buprenorphine dose on Day 1, or retention at the end of the first week. The findings of this study suggest that existing buprenorphine induction practices developed for heroin users appear to be equally effective with PO users. PMID- 22301085 TI - Addiction treatment-related employment barriers: the impact of methadone maintenance. AB - Employment is commonly upheld as an important outcome of addiction treatment. To explore this attribution, we assessed whether treatment enrollment predicts employment initiation among participants enrolled in a community-recruited Canadian cohort of people who inject drugs (IDU; N = 1,579). Survival analysis initially found no association between addiction treatment enrollment and employment initiation. However, when methadone maintenance therapy (MMT) was separated from other treatment modalities, non-MMT treatment positively predicted employment transitions, whereas MMT was negatively associated with employment initiation. Subanalyses examining transitions into temporary, informal, and under the-table income generation echo these results. Findings suggest that individual factors impacting employment transitions may systematically apply to MMT clients and that, in this setting, the impact of treatment on employment outcomes is contingent on treatment type and design. Treatment-specific differences underscore the need to expand low-threshold MMT, explore MMT alternatives, and evaluate the impact of treatment design on the social and economic activity of IDU. PMID- 22301086 TI - Two approaches to tailoring treatment for cultural minority adolescents. AB - At this time, compared with mainstream (Caucasian) youth, cultural minority adolescents experience more severe substance-related consequences and are less likely to receive treatment. Although several empirically supported interventions (ESIs), such as motivational interviewing (MI), have been evaluated with mainstream adolescents, fewer published studies have investigated the fit and efficacy of these interventions with cultural minority adolescents. In addition, many empirical evaluations of ESIs have not explicitly attended to issues of culture, race, and socioeconomic background in their analyses. As a result, there is some question about the external validity of ESIs, particularly in disadvantaged cultural minority populations. This review seeks to take a step toward filling this gap, by addressing how to improve the fit and efficacy of ESIs like MI with cultural minority youth. Specifically, this review presents the existing literature on MI with cultural minority groups (adult and adolescent), proposes two approaches for evaluating and adapting this (or other) behavioral interventions, and elucidates the rationale, strengths, and potential liabilities of each tailoring approach. PMID- 22301087 TI - Treating depression and substance use: a randomized controlled trial. AB - Few integrated substance use and depression treatments have been developed for delivery in outpatient substance abuse treatment settings. To meet the call for more "transportable" interventions, we conducted a pilot study to test a group cognitive-behavioral therapy (CBT) for depression and substance use that was designed for delivery by outpatient substance abuse treatment counselors. Seventy three outpatient clients were randomized to usual care enhanced with group CBT or usual care alone and assessed at three time points (baseline and 3 and 6 months postbaseline). Our results demonstrated that the treatment was acceptable and feasible for delivery by substance abuse treatment staff despite challenges with recruiting clients. Both depressive symptoms and substance use were reduced by the intervention but were not significantly different from the control group. These results suggest that further research is warranted to enhance the effectiveness of treatment for co-occurring disorders in these settings. PMID- 22301088 TI - LICSS - a chemical spreadsheet in microsoft excel. AB - BACKGROUND: Representations of chemical datasets in spreadsheet format are important for ready data assimilation and manipulation. In addition to the normal spreadsheet facilities, chemical spreadsheets need to have visualisable chemical structures and data searchable by chemical as well as textual queries. Many such chemical spreadsheet tools are available, some operating in the familiar Microsoft Excel environment. However, within this group, the performance of Excel is often compromised, particularly in terms of the number of compounds which can usefully be stored on a sheet. SUMMARY: LICSS is a lightweight chemical spreadsheet within Microsoft Excel for Windows. LICSS stores structures solely as Smiles strings. Chemical operations are carried out by calling Java code modules which use the CDK, JChemPaint and OPSIN libraries to provide cheminformatics functionality. Compounds in sheets or charts may be visualised (individually or en masse), and sheets may be searched by substructure or similarity. All the molecular descriptors available in CDK may be calculated for compounds (in batch or on-the-fly), and various cheminformatic operations such as fingerprint calculation, Sammon mapping, clustering and R group table creation may be carried out.We detail here the features of LICSS and how they are implemented. We also explain the design criteria, particularly in terms of potential corporate use, which led to this particular implementation. CONCLUSIONS: LICSS is an Excel-based chemical spreadsheet with a difference:* It can usefully be used on sheets containing hundreds of thousands of compounds; it doesn't compromise the normal performance of Microsoft Excel* It is designed to be installed and run in environments in which users do not have admin privileges; installation involves merely file copying, and sharing of LICSS sheets invokes automatic installation* It is free and extensibleLICSS is open source software and we hope sufficient detail is provided here to enable developers to add their own features and share with the community. PMID- 22301089 TI - Recent hybridization between Taenia asiatica and Taenia saginata. AB - Five Taenia tapeworms collected from humans in Tibetan Plateau, Sichuan, China, where three species of human Taenia are sympatrically endemic, were examined for the mitochondrial cox1 gene and two nuclear genes, ef1 and elp. Phylogenetic analyses of these genes revealed that two adult worms showed nuclear mitochondrial discordance, suggesting that they originated from hybridization between Taenia saginata and Taenia asiatica. One of two worms had T. asiatica type mtDNA, whereas another worm had T. saginata-type mtDNA, indicating that reciprocal hybridization between T. saginata and T. asiatica could occur. The worm having T. asiatica-type mtDNA was heterozygous at both nuclear loci with T. saginata-type alleles and T. asiatica-type alleles. In another worm, the ef1 locus was heterozygous with a T. saginata-type alleles and T. asiatica-type alleles, while the elp locus was homozygous with T. saginata-type alleles. Self fertilization is the main reproductive method of the genus Taenia. Since self fertilization represents a type of inbreeding, each locus in the offspring would become homozygous over generations with genetic drift. The fact that some nuclear loci are still heterozygous means that hybridization might have occurred recently. Hybridization between T. asiatica and T. saginata is probably an ongoing event in many areas in which they are sympatrically endemic. PMID- 22301090 TI - [About the article of S. Huard, S. Rochet, D. Lepage, P. Garbuio and L. Obert: New treatment of advanced Kienbock disease: replacement of lunate with costochondral autograft. Chir Main 2011;30(3):211-217]. PMID- 22301091 TI - Gastrostomy tube placement in gastric remnant at gastric bypass: a rat model for selective gut stimulation. AB - BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery achieves high remission rates of type 2 diabetes mellitus in obese diabetic patients. It has been hypothesized that the changes in bowel nutrient exposure after RYGB results in altered release of gut hormones and improved glucose homeostasis. Our objective was to assess the feasibility of, and report on, our technique and initial experience with selective gut stimulation in a gastric bypass rat model at an academic medical center in the United States. METHODS: We performed RYGB with simultaneous placement of a gastrostomy tube in the excluded gastric remnant in 8 obese Sprague-Dawley rats. A second group of 8 obese Sprague-Dawley rats underwent gastrostomy tube placement without gastric bypass and served as the controls. Each rat was tested for oral glucose tolerance preoperatively. On postoperative days 14 and 28, glucose tolerance was re-evaluated using the oral and gastrostomy tube routes. RESULTS: The gastrostomy tubes were successfully inserted in all the rats with no tube-related complications. The area under the curve after oral glucose gavage decreased significantly after gastric bypass (P = .01 at 14 d and P = .003 at 28 d). The gastric remnant glucose gavage after RYGB essentially reversed the effects of surgery on glucose metabolism. The areas under the curve showed no significant differences in the control group between the preoperative and postoperative oral or tube results. CONCLUSION: Placing a gastrostomy tube into the gastric remnant at RYGB in a rat model is technically feasible. Our initial findings support the role of duodenal exclusion in improving glucose metabolism after RYGB. PMID- 22301092 TI - Downsizing pregnancy complications: a study of paired pregnancy outcomes before and after bariatric surgery. AB - BACKGROUND: Overweight and obesity have been shown to be associated with increased adverse pregnancy outcomes. Weight reduction improves maternal health status and reduces the risk of pregnancy complications, as well as long-term consequences. Our objective was to compare the pregnancy outcomes of the same women who delivered before and after bariatric surgery. METHODS: A retrospective study comparing pregnancy outcomes, of the same women, delivered before and after a bariatric surgery was conducted. The observed deliveries occurred from 1988 to 2008 at Soroka University Medical Center, the sole tertiary hospital in the southern region of Israel. RESULTS: The present study included 288 paired pregnancies: 144 deliveries before and 144 after bariatric surgery. A significant reduction in the prepregnancy and predelivery maternal body mass index was noted after bariatric surgery (36.37 +/- 5.2 versus 30.50 +/- 5.4 kg/m(2), P < .001; and 40.15 +/- 4.92 versus 34.41 +/- 5.42 kg/m(2), P < .001; respectively). Only 8 patients (5.6%) were admitted during their pregnancy for bariatric complications. Pregnancy complications, such as hypertensive disorders (31.9% versus 16.6%; P = .004) and diabetes mellitus (20.8% versus 7.6%; P = .001), were significantly reduced after bariatric surgery. The rate of cesarean deliveries because of labor dystocia was significantly lower after bariatric surgery (5.6% versus 2.1%, P < .05). Using a multiple logistic regression model, controlling for maternal age, the reduction in hypertensive disorders (odds ratio .4, 95% confidence interval .2-.8) and diabetes mellitus (odds ratio .15, 95% confidence interval .1-.4) remained significant. CONCLUSION: A significant decrease in pregnancy complications, such as hypertensive disorders and diabetes mellitus, is achieved after bariatric surgery. PMID- 22301093 TI - [Free hospital choice does not mean less planning of services]. PMID- 22301094 TI - HIV-1 Tat protein impairs adipogenesis and induces the expression and secretion of proinflammatory cytokines in human SGBS adipocytes. AB - BACKGROUND: HIV-1 Tat protein has been shown to play multiple roles in the pathogenesis of AIDS; however, there is no information currently available on its effects on adipose tissue alterations. We have studied the effects of Tat on SGBS adipocytes to gain insight on its role on the development of lipodystrophy. METHODS: SGBS preadipocytes were exposed to Tat during and after differentiation. Acquisition of adipocyte morphology, expression of gene markers of adipogenesis and inflammation, release of adipokines and cytokines to the medium, and glucose uptake were measured. The action of Tat on tumour necrosis factor (TNF)-alpha regulated messenger RNA expression was determined in differentiated adipocytes. The capacity of rosiglitazone, resveratrol and parthenolide to influence the action of Tat was also assessed. RESULTS: Tat treatment reduced the number of SGBS preadipocytes that acquired adipocyte morphology. It also led to repression of adipogenic gene expression and induced the coordinate expression and release of proinflammatory cytokines in human adipose cells. Moreover, combined treatment with Tat and TNF-alpha produced an additive effect on the repression of adipocyte genes. The observed effects of Tat on gene transcription in adipocytes were due, in part, to TNF-alpha that was secreted as a consequence of intracellular exposure to Tat. CONCLUSIONS: Tat impairs adipogenesis in human SGBS preadipocytes and increases the expression and release of proinflammatory cytokines. Positive crosstalk between Tat and TNF-alpha contributes to the anti adipogenic and proinflammatory effects. HIV-1 Tat protein may play a role in the adipose tissue alterations that ultimately lead to lipoatrophy and systemic metabolic disturbances observed in HIV-1-infected patients. PMID- 22301095 TI - Reaction time as a measure of human associative learning. AB - Studies of human associative learning have often used causal/predictive learning preparations in which participants decide whether or not a first event is effective in causing or predicting a second event (i.e., an outcome). Those preparations have proved successful in replicating many Pavlovian phenomena. In the present paper we tested a novel associative learning preparation in which visually presented letters were paired with a visual outcome. Reaction times (RTs) were recorded to assess associative strength between specific cues and the outcome. Combining two different dependent variables (RTs and type of response given), we propose a rule for evaluating the associative strength between two events. The preparation and the data transformation rule were successful in producing several Pavlovian phenomena including excitatory acquisition, extinction, overshadowing, and latent inhibition, as well as established summation effects. Advantages and limitations of this new preparation based on the use of RT are discussed. PMID- 22301096 TI - Behavioral effects of bidirectional selection for behavior towards human in virgin and lactate Norway rats. AB - Although numerous studies have demonstrated strong differences in behavioral, hormonal and neurobiological characteristics between male rats selected for elimination (tame) and enhancement (aggressive) of aggressiveness towards humans, few studies have examined changes in female behavior under this selection. The objective of the current work was to evaluate the effects of bidirectional selection for aggressiveness towards humans on behavioral profiles of virgin and lactating rats compared with the behavior in tame, aggressive and unselected (wild-type) females. The behavior of virgin females was studied using the light dark box, the startle response test and the modified glove test. Tame females were less anxious and more tolerant towards humans than unselected and aggressive rats. Principal component analysis of all behavioral parameters produced three independent factors, explaining 66.37% of the total variability. The measures of behavior towards humans and the measures of anxiety mainly loaded on PC1 (first principal component) which separated the tame females from the unselected and aggressive ones. These data suggest the genetic correlation between the selected behavior towards humans and anxiety-related behavior in virgin rats. No significant effect of line was found for PC2 scores, associated with risk assessment behavior. Measurements of freezing behavior mainly loaded on PC3, and this component separated rats of different genetic groups from each other. The behavior of lactating rats was studied in maternal defense and pup retrieval tests. Females of selected lines did not significantly differ in behavioral measurements of these tests and were characterized by higher maternal motivation than unselected rats. It is suggested that long-term breeding of tame and aggressive rats in captivity has reduced the threshold for maternal behavior. PMID- 22301097 TI - Visual outcomes and safety of a small diameter intrastromal refractive inlay for the corneal compensation of presbyopia. AB - PURPOSE: To investigate the outcomes and safety of an intrastromal refractive inlay (Invue Lens, Biovision AG) for the corneal compensation of presbyopia. METHODS: This prospective, noncomparative, interventional clinical study comprised 45 emmetropic presbyopes with a mean age of 52.3 +/- 3.3 years (range: 47 to 58 years). The refractive inlay was inserted in the non-dominant eye within a corneal pocket that was created using a mechanical microkeratome. Last follow up was 12 months in all patients and examinations were scheduled at 1 week and 1, 3, 6, and 12 months after surgery. Visual, wavefront, contrast sensitivity, and topographic outcomes as well as structural corneal alteration were evaluated. RESULTS: Twelve months after surgery, uncorrected near visual acuity was 20/32 or better in 98% of operated eyes and binocularly, whereas uncorrected distance visual acuity was 20/40 or better in 93% of operated eyes and 20/25 or better in all patients binocularly. Three patients lost one line of corrected distance visual acuity in the operated eye. Overall, higher order aberrations were increased and contrast sensitivity was decreased in the operated eye. No tissue alterations were found using corneal confocal microscopy. No intra- or postoperative complications occurred. CONCLUSIONS: The intracorneal refractive inlay (Invue Lens) seems to be an effective surgical method for the corneal compensation of presbyopia in emmetropes aged between 45 and 60 years. PMID- 22301098 TI - Intraoperative cyclorotation and pupil centroid shift during LASIK and PRK. AB - PURPOSE: To determine the degree of cyclorotation and centroid shift in the x and y axis that occurs intraoperatively during LASIK and photorefractive keratectomy (PRK). METHODS: Intraoperative cyclorotation and centroid shift were measured in 63 eyes from 34 patients with a mean age of 34 years (range: 20 to 56 years) undergoing either LASIK or PRK. Preoperatively, an iris image of each eye was obtained with the VISX WaveScan Wavefront System (Abbott Medical Optics Inc) with iris registration. A VISX Star S4 (Abbott Medical Optics Inc) laser was later used to measure cyclotorsion and pupil centroid shift at the beginning of the refractive procedure and after flap creation or epithelial removal. RESULTS: The mean change in intraoperative cyclorotation was 1.48+/-1.11 degrees in LASIK eyes and 2.02+/-2.63 degrees in PRK eyes. Cyclorotation direction changed by >2 degrees in 21% of eyes after flap creation in LASIK and in 32% of eyes after epithelial removal in PRK. The respective mean intraoperative shift in the x axis and y axis was 0.13+/-0.15 mm and 0.17+/-0.14 mm, respectively, in LASIK eyes, and 0.09+/-0.07 mm and 0.10+/-0.13 mm, respectively, in PRK eyes. Intraoperative centroid shifts >100 MUm in either the x axis or y axis occurred in 71% of LASIK eyes and 55% of PRK eyes. CONCLUSIONS: Significant changes in cyclotorsion and centroid shifts were noted prior to surgery as well as intraoperatively with both LASIK and PRK. It may be advantageous to engage iris registration immediately prior to ablation to provide a reference point representative of eye position at the initiation of laser delivery. PMID- 22301099 TI - Unilateral sulcus implantation of the crystalens HD. AB - PURPOSE: To evaluate the results after unilateral sulcus implantation of the Crystalens HD (Bausch & Lomb) accommodative intraocular lens (IOL). METHODS: This retrospective interventional case series comprised six eyes from three patients who underwent cataract surgery and bilateral Crystalens HD accommodative IOL implantation. The Crystalens HD was implanted in the bag in one eye (non-sulcus group) and, due to posterior capsule rupture, the lens was positioned in the ciliary sulcus in the fellow eye (sulcus group). RESULTS: Mean patient age was 66.3 +/- 4.9 years (range: 60 to 72 years). Mean follow-up was 14.3 +/- 3.2 months (range: 12 to 18 months) for the non-sulcus group and 14 +/- 2 months (range: 12 to 16 months) for the sulcus group. Uncorrected distance visual acuity improved from 20/100 to 20/33 in the non-sulcus group and from 20/63 to 20/32 in the sulcus group during last follow-up. Corrected distance visual acuity improved from 20/35 to 20/20 in the non-sulcus group and from 20/27 to 20/23 in the sulcus group. Regarding near vision, all eyes in the sulcus group and 66.7% of eyes in the non-sulcus group achieved J1-J2 (Birkhauser reading chart). None of the eyes had any intra- (except posterior capsule rupture in the sulcus cases) or postoperative complications. CONCLUSIONS: Based on this small series, ciliary sulcus implantation of the Crystalens HD seems to be associated with no significant morbidity and provides satisfactory visual acuity outcomes. PMID- 22301100 TI - Change in epithelial thickness profile 24 hours and longitudinally for 1 year after myopic LASIK: three-dimensional display with Artemis very high-frequency digital ultrasound. AB - PURPOSE: To longitudinally follow epithelial thickness profile changes after myopic LASIK for 1 year to determine when and how epithelial changes occur and when epithelial stability is reached. METHODS: Epithelial thickness was measured with Artemis very high-frequency digital ultrasound (ArcScan Inc) across the central 10-mm corneal diameter in 11 eyes before and 1 day, and 1, 3, 6, and 12 months after myopic femtosecond LASIK. For each consecutive pair of time points, maps of the mean change in epithelial thickness and paired t test P value were plotted. RESULTS: Mean preoperative spherical equivalent refraction was -3.34 +/- 1.51 diopters (D) (range: -1.50 to -5.13 D). Overnight, there was a central 5-mm zone of epithelial thickening (0.5 to 1.5 MUm, P<.05) surrounded by epithelial thinning (4 to 6 MUm, P<.05) extending to the 8-mm zone. Between 1 day and 1 month, the epithelium thickened within the 7-mm zone by up to 5 MUm (P<.05) in a lenticular pattern with greater thickening centrally and progressively less thickening centrifugally. Between 1 and 3 months, the epithelium continued to thicken in the central 7-mm zone by approximately 1 MUm (P<.05). No change in epithelial thickness occurred after 3 months (P>.05). CONCLUSIONS: A lenticular change occurred in the epithelial thickness profile, with more thickening centrally than paracentrally; 22% of the total increase in central thickness occurred overnight, 58% between 1 day and 1 month, and 20% between 1 and 3 months, with stability between 3 and 12 months. The lenticular epithelial changes contribute to the observed myopic shift after myopic LASIK during the first 3 months. PMID- 22301101 TI - Bioactivity and prognostic significance of growth differentiation factor GDF15 secreted by bone marrow mesenchymal stem cells in multiple myeloma. AB - Overexpression of growth differentiation factor 15 (GDF15) by bone marrow mesenchymal stem cells occurs widely in patients with multiple myeloma, but the pathophysiologic effects of GDF15 in this setting remain undefined. GDF15 has been described in numerous solid tumors but never in hematologic malignancies. In this study, we report that GDF15 significantly increases survival of stroma dependent multiple myeloma cells including primary multiple myeloma cells. In particular, GDF15 conferred resistance to melphalan, bortezomib, and to a lesser extent, lenalidomide in both stroma-dependent and stroma-independent multiple myeloma cells. Akt-dependent signaling was critical to mediate the effects of GDF15, whereas Src and extracellular signal-regulated kinase 1/2 signaling pathways were not involved. Given these results, we tested the clinical significance of plasma concentrations of GDF15 (pGDF15) in 131 patients with multiple myeloma and found that it correlated with disease prognosis. Specifically, patients with high levels of pGDF15 had lower probabilities of event-free and overall survival 30 months after diagnosis than patients with low pGDF15 levels. Our findings suggest that tumor microenvironment-derived GDF15 is a key survival and chemoprotective factor for multiple myeloma cells, which is pathophysiologically linked to both initial parameters of the disease as well as patient survival. PMID- 22301102 TI - Is it valid to calculate the 3-kilohertz threshold by averaging 2 and 4 kilohertz? AB - Many guidelines for reporting hearing results use the threshold at 3 kilohertz (kHz), a frequency not measured routinely. This study assessed the validity of estimating the missing 3-kHz threshold by averaging the measured thresholds at 2 and 4 kHz. The estimated threshold was compared to the measured threshold at 3 kHz individually and when used in the pure-tone average (PTA) of 0.5, 1, 2, and 3 kHz in audiometric data from 2170 patients. The difference between the estimated and measured thresholds for 3 kHz was within +/- 5 dB in 72% of audiograms, +/- 10 dB in 91%, and within +/- 20 dB in 99% (correlation coefficient r = 0.965). The difference between the PTA threshold using the estimated threshold compared with using the measured threshold at 3 kHz was within +/- 5 dB in 99% of audiograms (r = 0.997). The estimated threshold accurately approximates the measured threshold at 3 kHz, especially when incorporated into the PTA. PMID- 22301103 TI - Atypical mycobacterium detection in refractory chronic rhinosinusitis. AB - OBJECTIVES: Atypical mycobacterium (AM) involvement in refractory chronic rhinosinusitis (CRS) is sought by some surgeons with customary acid-fast bacilli cultures (AFBC) in the operating room (OR). We evaluate our experience with AM in CRS by describing (1) associated risk factors, (2) species identified, and (3) frequency of positive cultures in clinic versus OR. STUDY DESIGN: Case series with chart review. SETTING: Tertiary rhinology practice. SUBJECTS AND METHODS: AFBC taken between 2005 and 2011 were identified from a microbiology laboratory database. Charts were reviewed for gender, age, medical history, risk factors for AM, pathogen types, and treatments, with statistical comparison using Pearson chi(2). The benefit of "targeted AFBC" for cases with high clinical suspicion was compared with "customary AFBC" in the OR. RESULTS: Thirty-seven patients were identified with AM, of which 10 had one or more risk factors for AM including foreign body (n = 4), non-HIV immune dysfunction (n = 4), and previous chemoradiation (n = 4). Six different AM species were identified: most frequently Mycobacterium abscessus (57.1%), followed by Mycobacterium avium-intracellulare complex (14.3%) and Mycobacterium chelonae (14.3%). "Targeted AFBC" from the outpatient setting were positive in 10 of 190 (5.3%) patients, whereas 10 of 373 (2.6%) patients of "customary AFBC" in the OR were positive (P = .12). Macrolide therapy was employed in 23 of 37 (62%) patients with AM-associated CRS but was not prescribed in patients with positive "customary AFBC" alone. CONCLUSION: AM associated CRS is an uncommon condition that can occur in the absence of foreign body or overtly altered innate/adaptive immunity. Indications and efficacy of macrolide therapy, as well as the potential relationships between existence of AM in tap water, AM biofilms, and frequent use of nasal irrigations warrant further investigation in refractory CRS. PMID- 22301104 TI - The value of routine pH monitoring in the diagnosis and treatment of laryngopharyngeal reflux. AB - OBJECTIVE: To assess the need for pH testing in diagnosing laryngopharyngeal reflux (LPR). STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary care center. SUBJECTS AND METHODS: On the basis of symptoms and/or abnormal endoscopic findings, more than 500 patients underwent 24-hour pharyngeal pH testing at a single center (using the Dx-pH probe) between January 2009 and June 2011. A total of 163 patients not on proton-pump inhibitors at the time of study and with complete data available for analysis (pH results, body mass index, smoking status, pretest reflux symptom index) were divided into 2 groups by positive (n = 70) and negative (n = 93) Ryan Score. The Reflux Symptom Index (RSI) was compared between groups and assessed overall against Ryan Score parameters at different pH thresholds. The diagnostic utility of an RSI >= 13 for prediction of Ryan Score was assessed. RESULTS: No significant difference in RSI was seen between Ryan-positive (17.50 +/- 11.47) and Ryan-negative (14.95 +/- 11.43) patients (P = .161). Overall, RSI correlated poorly with percentage time spent below pH thresholds 6.5, 6.0, 5.5, and 5.0 and upright and supine Ryan parameters at these thresholds (as determined by linear regression analysis). The sensitivity, specificity, positive predictive value, and negative predictive value of RSI >= 13 for Ryan positivity were 55.7%, 47.3%, 44.3%, and 58.7%, respectively. CONCLUSION: Our findings show that in our population of otolaryngology patients, the diagnosis of LPR cannot be reliably made on the basis of symptoms alone. Diagnosis, and in particular treatment decisions, should ideally be made on the basis of a combination of symptoms, signs, and confirmatory testing. PMID- 22301105 TI - Does mannose-binding lectin have a role in adult Turkish patients with nasal polyposis? AB - OBJECTIVE: Mannose-binding lectin is an important component of innate immunity; it initiates the lectin pathway of complement activation critical for innate immunity. Failure of local innate defenses may result in defective responses that lead to the persistent carriage of microorganisms or ongoing inflammation. This study investigated the role of mannose-binding lectin levels and the frequency of the 6 functional mannose-binding lectin polymorphisms in Turkish individuals with nasal polyposis. STUDY DESIGN: A case-control study. SETTING: University hospital. SUBJECTS AND METHODS: Fifty-one patients with nasal polyposis and 53 healthy controls were enrolled. Serum mannose-binding lectin levels were obtained by enzyme-linked immunosorbent assay (ELISA) using the mannose-binding lectin oligomer ELISA kit. Mannose-binding lectin 2 genotyping was performed by isolating the genomic DNA from leukocytes. RESULTS: Mean mannose-binding lectin levels were 1693.2 and 1887.8 in the patient and control group, respectively. Although mannose-binding lectin levels were lower in the patient group, the difference was not statistically significant (P > .05). No overall association was observed between the mannose-binding lectin genotype and susceptibility to nasal polyposis (95% confidence interval = 0.716-4.389, odds ratio = 1.773). The mutant allele frequencies of the 3 structural polymorphisms did not differ significantly between the nasal polyposis patients and the controls (P = .659). CONCLUSIONS: Mannose-binding lectins are not involved in the pathogenesis of nasal polyposis in adult Turkish patients, but additional research is needed for further comment. PMID- 22301106 TI - Factors associated with revision adenoidectomy. AB - OBJECTIVE: To determine whether patient factors (eg, indication for initial surgery, medical comorbidity, or age) are associated with adenoid regrowth and subsequent need for revision adenoidectomy and whether surgical factors (eg, surgical technique or level of surgeon's training) are associated with adenoid regrowth and subsequent need for revision adenoidectomy. STUDY DESIGN: Historical cohort study. SETTING: Tertiary care academic medical center. SUBJECTS AND METHODS: Children (<=18 years) who underwent adenoidectomy or adenotonsillectomy between 1980 and May 2009 were identified. Medical and surgical records were reviewed for sex, age at surgery, indication for surgery, training level of surgeon, surgical technique, and history of allergies, asthma, or gastroesophageal reflux disease. RESULTS: Of 8245 surgical cases (53.8% male), 163 were revision adenoidectomies. Age at initial adenoidectomy was a significant factor for revision adenoidectomy, with younger ages associated with higher increased risk. Indication for adenoidectomy was also a significant risk factor; adjusted for age, patients with ear rather than infectious indications were about 10 times more likely to require revision. A diagnosis of gastroesophageal reflux disease was a significant risk factor (hazard ratio, 2.23; P = .002). CONCLUSION: Several risk factors are associated with revision adenoidectomy: young age at initial procedure, indication for adenoidectomy, and diagnosis of gastroesophageal reflux disease. Surgical technique, level of experience of the initial surgeon, and diagnosis of asthma or allergies were not significant risk factors for revision adenoidectomy. PMID- 22301107 TI - Advance II: a prospective, randomized study assessing safety and efficacy of bioabsorbable steroid-releasing sinus implants. AB - OBJECTIVE: Endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) may be compromised by postoperative inflammation, polyposis, and adhesions, often requiring subsequent intervention. To address this issue, the authors investigated the safety and effectiveness of controlled delivery of mometasone furoate to the sinus mucosa via bioabsorbable implants deployed at the time of ESS. STUDY DESIGN: Prospective, multicenter, randomized, controlled, double-blind trial using an intrapatient control design. SETTING: Otolaryngology-head and neck surgery centers; both academic and private practices. SUBJECTS AND METHODS: The study enrolled 105 patients with CRS undergoing bilateral ethmoidectomy to compare the effect of drug-releasing to non-drug-releasing implants using an intrapatient control design. Postoperative interventions, polyposis, and adhesions were assessed postoperatively. Efficacy was determined through independent analysis of randomized video-endoscopies by 3 blinded sinus surgeons. Safety assessments included ocular examinations. RESULTS: Implants were successfully deployed in all 210 ethmoid sinuses. Compared with control sinuses with non-drug-releasing implants, the drug-releasing implant provided a 29.0% relative reduction in postoperative interventions (P = .028) and a 52% (P = .005) decrease in lysis of adhesions. The relative reduction in frank polyposis was 44.9% (P = .002). Similar reductions were observed in real-time grading performed by the clinical investigators. No clinically significant changes from baseline in intraocular pressure or cataracts were observed. CONCLUSION: This study provides a high level of evidence that use of steroid-releasing implants that apply a sustained release of corticosteroid improves surgical outcomes by reducing synechiae formation, polyposis, and the need for postoperative interventions, with no observable ocular safety risk. PMID- 22301108 TI - Evidence of maxillary sinus inflammation in seasonal allergic rhinitis. AB - OBJECTIVE: Allergic rhinitis has been frequently associated with both acute and chronic sinusitis. Previous studies have shown an influx of eosinophils into the maxillary sinus after nasal challenge with allergen. The objective of this study was to determine, in humans, if the development of seasonal allergic inflammation, secondary to natural allergen exposure, leads to similar inflammation within the maxillary sinus. STUDY DESIGN: Prospective, longitudinal study. Setting. Academic medical center and research laboratory. SUBJECTS AND METHODS: Eighteen subjects were evaluated in and out of the ragweed allergy season using subjective measures (nasal symptoms, quality of life), nasal secretory response to methacholine challenge, and evaluation of biomarkers in nasal and sinus lavages. RESULTS: The subjects became symptomatic during the season and reported worse quality of life and increased nasal reactivity to methacholine. The total number of eosinophils obtained by nasal lavage during the season (median= 35,691) was significantly higher compared with out of season (median = 2811, P <= .02). Similarly, there were significantly more eosinophils, albeit to a lesser magnitude, in the maxillary sinus during the season (median = 4248) compared with the out-of-season samples (median = 370, P <= .02). CONCLUSION: The authors provide evidence that natural exposure to pollen during an individual's allergy season leads to both nasal and sinus inflammation, strengthening the association between allergic rhinitis and sinusitis. The mechanism of this inflammatory response needs to be elucidated. PMID- 22301109 TI - Ursodeoxycholate modulates bile flow and bile salt pool independently from the cystic fibrosis transmembrane regulator (Cftr) in mice. AB - Cystic fibrosis liver disease (CFLD) is treated with ursodeoxycholate (UDCA). Our aim was to evaluate, in cystic fibrosis transmembrane regulator knockout (Cftr(-/ )) mice and wild-type controls, whether the supposed therapeutic action of UDCA is mediated via choleretic activity or effects on bile salt metabolism. Cftr(-/-) mice and controls, under general anesthesia, were intravenously infused with tauroursodeoxycholate (TUDCA) in increasing dosage or were fed either standard or UDCA-enriched chow (0.5% wt/wt) for 3 wk. Bile flow and bile composition were characterized. In chow-fed mice, we analyzed bile salt synthesis and pool size of cholate (CA). In both Cftr(-/-) and controls intravenous TUDCA stimulated bile flow by ~250% and dietary UDCA by ~500%, compared with untreated animals (P < 0.05). In non-UDCA-treated Cftr(-/-) mice, the proportion of CA in bile was higher compared with that in controls (61 +/- 4 vs. 46 +/- 4%; P < 0.05), accompanied by an increased CA synthesis [16 +/- 1 vs. 10 +/- 2 MUmol.h(-1).100 g body wt (BW)(-1); P < 0.05] and CA pool size (28 +/- 3 vs. 19 +/- 1 MUmol/100 g BW; P < 0.05). In both Cftr(-/-) and controls, UDCA treatment drastically reduced the proportion of CA in bile below 5% and diminished CA synthesis (2.3 +/- 0.3 vs. 2.2 +/- 0.4 MUmol.day(-1).100 g BW(-1); nonsignificant) and CA pool size (3.6 +/- 0.6 vs. 1.5 +/- 0.3 MUmol/100 g BW; P < 0.05). Acute TUDCA infusion and chronic UDCA treatment both stimulate bile flow in cystic fibrosis conditions independently from Cftr function. Chronic UDCA treatment reduces the hydrophobicity of the bile salt pool in Cftr(-/-) mice. These results support a potential beneficial effect of UDCA on bile flow and bile salt metabolism in cystic fibrosis conditions. PMID- 22301110 TI - TNF-alpha induces upregulation of EGFR expression and signaling in human colonic myofibroblasts. AB - The myofibroblast has recently been identified as an important mediator of tumor necrosis factor-alpha (TNF-alpha)-associated colitis and cancer, but the mechanism(s) involved remains incompletely understood. Recent evidence suggests that TNF-alpha is a central regulator of multiple inflammatory signaling cascades. One important target of TNF-alpha may be the signaling pathway downstream of the epidermal growth factor receptor (EGFR), which has been associated with many human cancers. Here, we show that long-term exposure of 18Co cells, a model of human colonic myofibroblasts, with TNF-alpha led to a striking increase in cell surface EGFR expression, an effect that was completely inhibited by cycloheximide. Subsequent EGFR binding by EGF and heparin binding (HB)-EGF was associated with enhanced EGFR tyrosine kinase activity, prolonged ERK activation, and a significant increase in cyclooxygenase-2 (COX-2) expression compared with 18Co cells treated with EGF and HB-EGF alone. TNF-alpha also increased EGFR expression and signaling in primary myofibroblasts isolated from human colon tissue. TNF-alpha-induced upregulation of EGFR may be a plausible mechanism to explain the exaggerated cellular responsiveness that characterizes inflammatory bowel disease and that may contribute to a microenvironment that predisposes to colitis-associated cancer through enhanced COX-2 expression. PMID- 22301111 TI - Platelets orchestrate remote tissue damage after mesenteric ischemia-reperfusion. AB - Ischemia-reperfusion (I/R) injury is a leading cause of morbidity and mortality. A functional role for platelets in tissue damage after mesenteric I/R is largely unknown. The hypothesis that mesenteric I/R local and remote injury are platelet dependent was tested. Using a murine mesenteric I/R model, we demonstrate that platelets orchestrate remote lung tissue damage that follows mesenteric I/R injury and also contribute, albeit to a lesser degree, to local villi damage. While lung damage is delayed compared with villi damage, it increased over time and was characterized by accumulation of platelets in the pulmonary vasculature early, followed by alveolar capillaries and extravasation into the pulmonary space. Both villi and lung tissues displayed complement deposition. We demonstrate that villi and lung damage are reduced in mice made platelet deficient before I/R injury and that platelet transfusion into previously platelet-depleted mice before I/R increased both villi and lung tissue damage. Increased C3 deposition accompanied platelet sequestration in the lung, which was mostly absent in platelet-depleted mice. In contrast, C3 deposition was only minimally reduced on villi of platelet-depleted mice. Our findings position platelets alongside complement as a significant early upstream component that orchestrates remote lung tissue damage after mesenteric I/R and strongly suggest that reperfusion injury mitigating modalities should consider the contribution of platelets. PMID- 22301112 TI - The decreased expression of Beclin-1 correlates with progression to esophageal adenocarcinoma: the role of deoxycholic acid. AB - Beclin-1 has a central role in the regulation of autophagy. Barrett's esophagus (BE) is associated with a significantly increased risk for the development of esophageal adenocarcinoma (EAC). In the current study, we evaluated the role of Beclin-1 and autophagy in the EAC. Biopsies obtained from patients with BE and EAC, tissues from a rat model of BE and EAC, and esophageal cell lines were evaluated for the expression of Beclin-1 by immunohistochemistry, immunoblotting, or RT-PCR. Since reflux of bile acids is important in EAC, we also evaluated the effect of exposure to deoxycholic acid (DCA) on autophagy and Beclin-1 expression. Beclin-1 expression was high in squamous epithelium and nondysplastic BE, whereas its expression was low in dysplastic BE and EAC. The same pattern of expression was observed in rat tissues and in esophageal cell lines. Normal esophageal epithelium and HET-1A cells (derived from normal squamous epithelium) show high levels of Beclin-1, but lower levels of Beclin-1 were found in BE and EAC cell lines (CP-A, CP-C, and OE33). Acute exposure to DCA led to increased Beclin-1 expression and increased autophagy as evaluated by electron microscopy and counting percentage of GFP-LC3-positive BE cells with punctate pattern. In contrast, chronic exposure to DCA did not result in the alteration of Beclin-1 levels or autophagy. In summary, these data suggest that autophagy is initially activated in response to bile acids, but chronic exposure to bile acids leads to decreased Beclin-1 expression and autophagy resistance. PMID- 22301113 TI - Preproendothelin-1 expression is negatively regulated by IFNgamma during hepatic stellate cell activation. AB - Endothelin-1 (ET-1), a powerful vasoconstrictor peptide, is produced by activated hepatic stellate cells (HSC) and promotes cell proliferation, fibrogenesis, and contraction, the latter of which has been thought to be mechanistically linked to portal hypertension in cirrhosis. Interferon-gamma (IFNgamma), a Th1 cytokine produced by T cells, inhibits stellate cell proliferation, fibrogenesis, and muscle-specific gene expression. Whether IFNgamma-induced inhibitory effects are linked to regulation of ET-1 expression in activated stellate cells remains unknown. Here we examined IFNgamma's effects on preproET-1 mRNA expression and the signaling pathways underlying this process. We demonstrated that preproET-1 mRNA expression in HSCs was prominently increased during cell culture-induced activation; IFNgamma significantly inhibited both preproET-1 mRNA expression and ET-1 peptide production. Similar results were found in an in vivo model of liver injury and intraperitoneal administration of IFNgamma. PreproET-1 promoter analysis revealed that IFNgamma-induced inhibition of preproET-1 mRNA expression was closely linked to the AP-1 and Smad3 signaling pathways. Furthermore, IFNgamma reduced JNK phosphorylation, which tightly was associated with decreased phosphorylation of downstream factors c-Jun and Smad3 and decreased binding activity of c-Jun and Smad3 in the preprpET-1 promoter. Importantly, IFNgamma reduced both c-Jun mRNA and protein levels. Given the important role of ET-1 in wound healing, our results suggest a novel negative signaling network by which IFNgamma inhibits preproET-1 expression, highlighting one potential molecular mechanism for IFNgamma-induced host immunomodulation of liver fibrogenesis. PMID- 22301114 TI - The endocannabinoid N-arachidonoyl dopamine (NADA) selectively induces oxidative stress-mediated cell death in hepatic stellate cells but not in hepatocytes. AB - The endocannabinoid system is a crucial regulator of hepatic fibrogenesis. We have previously shown that the endocannabinoid anandamide (AEA) is a lipid mediator that blocks proliferation and induces death in hepatic stellate cells (HSCs), the main fibrogenic cell type in the liver, but not in hepatocytes. However, the effects of other endocannabinoids such as N-arachidonoyl dopamine (NADA) have not yet been investigated. The NADA-synthesizing enzyme tyrosine hydroxylase was mainly expressed in sympathetic neurons in portal tracts. Its expression pattern stayed unchanged in normal or fibrotic liver. NADA dose dependently induced cell death in culture-activated primary murine or human HSCs after 2-4 h, starting from 5 MUM. Despite caspase 3 cleavage, NADA-mediated cell death showed typical features of necrosis, including ATP depletion. Although the cannabinoid receptors CB1, CB2, or transient receptor potential cation channel subfamily V, member 1 were expressed in HSCs, their pharmacological or genetic blockade failed to inhibit NADA-mediated death, indicating a cannabinoid-receptor independent mechanism. Interestingly, membrane cholesterol depletion with methyl beta-cyclodextrin inhibited AEA- but not NADA-induced death. NADA significantly induced reactive oxygen species formation in HSCs. The antioxidant glutathione (GSH) significantly decreased NADA-induced cell death. Similar to AEA, primary hepatocytes were highly resistant against NADA-induced death. Resistance to NADA in hepatocytes was due to high levels of GSH, since GSH depletion significantly increased NADA-induced death. Moreover, high expression of the AEA-degrading enzyme fatty acid amide hydrolase (FAAH) in hepatocytes also conferred resistance towards NADA-induced death, since pharmacological or genetic FAAH inhibition significantly augmented hepatocyte death. Thus the selective induction of cell death in HSCs proposes NADA as a novel antifibrogenic mediator. PMID- 22301115 TI - Development of the Risk Assessment Suicidality Scale (RASS): a population-based study. AB - BACKGROUND: Suicide and suicide attempts are significant and costly public health problems. In order to prevent suicidal and other self-injurious behaviors, research on the multiple factors involved in these behaviors with comprehensive and user-friendly instruments is necessary. The aim of the current study was to construct a self-report instrument with emphasis on items describing suicide related behavior itself rather than strongly related clinical features on the basis of a general population study. METHODS: Twelve items comprising a new scale were applied to 734 subjects from the general population (40.6% males and 59.4% females) aged 40.8+/-11.5 along with the STAI and the CES-D. RESULTS: The scoring method was developed on the basis of frequency table of responses to the individual scale items. The factor analysis returned 3 factors explaining 59.19% of total variance (Intention, Life, and History). The Cronbach's alpha was 0.85 for the Intention, 0.69 for the Life and 0.52 for the History subscale. LIMITATION: The findings need replication in clinical and epidemiologic studies. CONCLUSION: The RASS is a reliable and valid instrument which might prove valuable in the assessment of suicidal risk in the general population as well as in mental patients. PMID- 22301116 TI - Reduced temporal mismatch negativity in late-life depression: an event-related potential index of cognitive deficit and functional disability? AB - BACKGROUND: Depression in older people has been consistently linked with a variety of neurobiological brain changes. One measure of preattentive auditory processing, the mismatch negativity (MMN), has not been previously examined in late-life depression. This study examined MMN elicited by duration deviant stimuli in older people with lifetime depression, and explored its relationship with neuropsychological functioning and disability. METHODS: Twenty-two older health-seeking patients (mean age=65.2 years) with lifetime major depressive disorder and twelve age and sex-matched control participants (mean age=64.6 years) completed detailed clinical and neuropsychological assessments and the WHO DAS as a measure of disability. MMN amplitudes were elicited using a two-tone passive auditory oddball paradigm and measured at frontal (Fz), central (Cz) and temporal (left and right mastoid: M1 and M2, respectively) sites. RESULTS: Patients with depression demonstrated reduced mean MMN amplitude at temporal (M1, t=3.1, p<0.01; M2, t=3.8, p<0.01), but not fronto-central sites. Reduced temporal MMN amplitudes did not relate to depressive symptom severity, but were associated with reduced semantic fluency and greater self-rated functional disability. LIMITATIONS: The contribution of depressive symptom 'state' and medications on MMN need to be considered. CONCLUSIONS: Reduced mean amplitudes of mastoid MMN in older patients with lifetime depression may reflect underlying brain changes. This preattentive marker relates to neuropsychological probes of frontotemporal circuits, and importantly, is associated with disability. Longitudinal analysis of MMN in this group will determine its predictive utility as a biomarker for ongoing cognitive decline and illness chronicity. PMID- 22301117 TI - Increased QT interval dispersion predicts 15-year cardiovascular mortality in type 2 diabetic subjects: the population-based Casale Monferrato Study. AB - OBJECTIVE: To evaluate the predictive role of increased corrected QT (QTc) and QT interval dispersion (QTd) on all-cause and cardiovascular mortality in a large, unselected type 2 diabetic population. RESEARCH DESIGN AND METHODS: The prospective study included 1,357 type 2 diabetic patients from the Casale Monferrato Study. At baseline, QTc intervals >0.44 s and QTd intervals >0.08 s were considered abnormally prolonged. Both all-cause and cardiovascular mortality were assessed 15 years after the baseline examination. RESULTS: During the follow up period, 862 subjects per 12,450 person-years died. Multivariate analysis showed that the hazard ratio (HR) of cardiovascular mortality was significantly increased in subjects with prolonged QTd (1.26 [95% CI 1.02-1.55]) and was only slightly reduced after multiple adjustments. Conversely, prolonged QTc did not increase the HRs for all-cause or cardiovascular mortality. CONCLUSIONS: Increased QTd predicts cardiovascular mortality after a long-term follow-up period in a large, unselected population of type 2 diabetic subjects. PMID- 22301118 TI - Association of coexisting diabetes and depression with mortality after myocardial infarction. AB - OBJECTIVE: Diabetes and depression are both linked to an increased mortality risk after myocardial infarction (MI). Population-based studies suggest that having both diabetes and depression results in an increased mortality risk, beyond that of having diabetes or depression alone. The purpose of this study was to examine the joint association of diabetes and depression with mortality in MI patients. RESEARCH DESIGN AND METHODS: Data were derived from two multicenter cohort studies in the Netherlands, comprising 2,704 patients who were hospitalized for MI. Depression, defined as a Beck Depression Inventory score >=10, and diabetes were assessed during hospitalization. Mortality data were retrieved for 2,525 patients (93%). RESULTS: During an average follow-up of 6.2 years, 439 patients died. The mortality rate was 14% (226 of 1,673) in patients without diabetes and depression, 23% (49 of 210) in patients with diabetes only, 22% (118 of 544) in patients with depression only, and 47% (46 of 98) in patients with both diabetes and depression. After adjustment for age, sex, smoking, hypertension, left ventricular ejection fraction, prior MI, and Killip class, hazard ratios for all cause mortality were 1.38 (95% CI 1.00-1.90) for patients with diabetes only, 1.39 (1.10-1.76) for patients with depression only, and as much as 2.90 (2.07 4.07) for patients with both diabetes and depression. CONCLUSIONS: We observed an increased mortality risk in post-MI patients with both diabetes and depression, beyond the association with mortality of diabetes and depression alone. PMID- 22301119 TI - East Africans in Sweden have a high risk for type 1 diabetes. AB - OBJECTIVE: To investigate the prevalence of type 1 diabetes in children with an origin in Sub-Saharan Africa in Sweden. RESEARCH DESIGN AND METHODS: Nationwide register study based on retrieved prescriptions of insulin during 2009 in children aged 0-18 years. The study population consisted of 35,756 children in families with an origin in Sub-Saharan Africa and 1,666,051 children with native Swedish parents. RESULTS: The odds ratio (OR) for insulin medication in Swedish born children in families originating in East Africa was 1.29 (95% CI 1.02-1.63) compared with offspring of native Swedish parents, after adjustment for age and sex, and less common in children who themselves were born in East Africa: 0.50 (0.34-0.73). Offspring of parents from other parts of Sub-Saharan Africa had a comparatively low risk for insulin medication. CONCLUSIONS: This study indicates that Swedish-born children with an origin in East Africa have a high risk of type 1 diabetes. PMID- 22301120 TI - Impact of diabetes among revascularized patients in Japan and the U.S. AB - OBJECTIVE: Approximately 25% of patients who undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) have diabetes, and the diagnosis of diabetes roughly doubles the mortality risk associated with coronary artery disease. However, the impact of diabetes may differ according to ethnicity. Our objective was to examine the impact of diabetes on long-term survival among U.S. and Japanese patients who underwent PCI or CABG. RESEARCH DESIGN AND METHODS: For the current analysis, we included 8,871 patients from a Japanese multicenter registry (Coronary Revascularization Demonstrating Outcome database in Kyoto; median follow-up 3.5 years; interquartile range [IQR] 2.6-4.3) and 7,229 patients from a U.S. multipractice registry (Texas Heart Institute Research Database; median follow-up 5.2 years; IQR 3.8-6.5). RESULTS: Diabetes was more prevalent among Japanese than U.S. patients (39.2 vs. 31.0%; P < 0.001). However, after revascularization, long-term all-cause mortality was lower in diabetic Japanese patients than in diabetic U.S. patients (85.4 vs. 82.2%; log rank test P = 0.009), whereas it was similar in nondiabetic Japanese and U.S. patients (89.1 vs. 89.5%; P = 0.50). The national difference in crude mortality was also significant among insulin-using patients with diabetes (80.8 vs. 74.9%; P = 0.023). When long-term mortality was adjusted for known predictors, U.S. location was associated with greater long-term mortality risk than Japanese location among nondiabetic patients (hazard ratio 1.58 [95% CI 1.32-1.88]; P < 0.001) and, especially, diabetic patients (1.88 [1.54-2.30]; P < 0.001). CONCLUSIONS: Although diabetes was less prevalent in U.S. patients than in Japanese patients, U.S. patients had higher overall long-term mortality risk. This difference was more pronounced in diabetic patients. PMID- 22301121 TI - Distinguishing colonization from infection with Staphylococcus aureus in diabetic foot ulcers with miniaturized oligonucleotide arrays: a French multicenter study. AB - OBJECTIVE: To extend our previous work on evaluating the use of oligonucleotide arrays to discriminate colonization from infection owing to Staphylococcus aureus in diabetic foot ulcers (DFUs). RESEARCH DESIGN AND METHODS: Patients admitted to 14 French diabetic foot departments for a DFU were screened for entry into the study. At admission, ulcers were classified based on clinical examination according to the Infectious Diseases Society of America system. Only patients with monomicrobial culture for S. aureus were included. In persons with an uninfected ulcer, a second wound bacterial specimen was obtained 1 month later. Using oligonucleotide arrays, S. aureus resistance and virulence genes were determined, and each isolate was affiliated to a clonal complex (CC). RESULTS: S. aureus was initially isolated from 75 uninfected and 120 infected ulcers; 35 were methicillin resistant. A total of 44 (59%) strains from uninfected DFUs belonged to CC5/CC8 clones vs. 6 (5%) from infected DFUs (P < 0.001). During follow-up, 57 (76%) of uninfected DFUs healed or had a favorable outcome; the strain in 49 (86%) of them belonged to CC5/CC8. Conversely, 18 (24%) had a poor outcome but not a single strain belonged to CC5/CC8 clone. Moreover, lukDE was significantly associated with a favorable outcome of the wound. CONCLUSIONS: As suggested by our previous study, the use of DNA arrays appears to be a promising technique that might help distinguishing uninfected from infected wounds, predicting ulcer outcome and then contributing to a more adequate use of antibiotics. PMID- 22301122 TI - Effect of glycemic control on sudomotor denervation in type 2 diabetes. AB - OBJECTIVE: Sudomotor symptoms are a common component of diabetic autonomic neuropathy, but the pathology of sudomotor innervation and its relationship with glycemic control have remained obscured. RESEARCH DESIGN AND METHODS: We enrolled 42 patients (26 males and 16 females aged 56.64 +/- 12.67 years) with diabetic neuropathy defined by symmetric distally predominant sensory symptoms, abnormal nerve conduction studies, and reduced intraepidermal nerve fiber density in the leg. Skin biopsies of the distal leg were immunostained with antiprotein gene product 9.5 for nerve fibers and counterstained with Congo red for sweat glands. Sweat gland innervation index (SGII) was quantified with a new computerized area based morphometric system. RESULTS: Protein gene product 9.5(+) nerve terminals surrounded secretory coils of the sweat glands in the skin of control subjects. Sudomotor denervation was present in diabetic patients, manifesting as depletion of periglandular nerve fibers with lower SGII compared with 42 age- and sex matched control subjects (2.54 +/- 1.87 vs. 4.68 +/- 1.51%, P < 0.001). The SGII was correlated with HbA(1c) (P = 0.011) and was lower in patients with anhidrosis of the feet compared with those with normal sweating of the feet (0.82 +/- 0.69 vs. 3.00 +/- 1.81%, P = 0.001). Sudomotor denervation was concordant with cardiac autonomic dysfunction as assessed with reduced heart rate variability (P = 0.003). CONCLUSIONS: Sudomotor denervation is a significant presentation of diabetic neuropathy, and the SGII was associated with HbA(1c). A skin biopsy offers a structural assessment of sudomotor innervation. PMID- 22301123 TI - Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: associations of maternal A1C and glucose with pregnancy outcomes. AB - OBJECTIVE: To compare associations of maternal glucose and A1C with adverse outcomes in the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and determine, based on those comparisons, if A1C measurement can provide an alternative to an oral glucose tolerance test (OGTT) in pregnant women. RESEARCH DESIGN AND METHODS: Eligible pregnant women underwent a 75-g OGTT at 24 32 weeks' gestation. A sample for A1C was also collected. Neonatal anthropometrics and cord serum C-peptide were measured. Associations with outcomes were assessed using multiple logistic regression with adjustment for potential confounders. RESULTS: Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, 21,064 had a nonvariant A1C result. The mean +/- SD A1C was 4.79 +/- 0.40%. Associations were significantly stronger with glucose measures than with A1C for birth weight, sum of skinfolds, and percent body fat >90th percentile and for fasting and 1-h glucose for cord C-peptide (all P < 0.01). For example, in fully adjusted models, odds ratios (ORs) for birth weight >90th percentile for each measure higher by 1 SD were 1.39, 1.45, and 1.38, respectively, for fasting, 1-, and 2-h plasma glucose and 1.15 for A1C. ORs for cord C-peptide >90th percentile were 1.56, 1.45, and 1.35 for glucose, respectively, and 1.32 for A1C. ORs were similar for glucose and A1C for primary cesarean section, preeclampsia, and preterm delivery. CONCLUSIONS: On the basis of associations with adverse outcomes, these findings suggest that A1C measurement is not a useful alternative to an OGTT in pregnant women. PMID- 22301124 TI - Age-related loss of brain volume and T2 relaxation time in youth with type 1 diabetes. AB - OBJECTIVE: 2 Childhood-onset type 1 diabetes is associated with neurocognitive deficits, but there is limited evidence to date regarding associated neuroanatomical brain changes and their relationship to illness variables such as age at disease onset. This report examines age-related changes in volume and T2 relaxation time (a fundamental parameter of magnetic resonance imaging that reflects tissue health) across the whole brain. RESEARCH DESIGN AND METHODS: Type 1 diabetes, N = 79 (mean age 20.32 +/- 4.24 years), and healthy control participants, N = 50 (mean age 20.53 +/- 3.60 years). There were no substantial group differences on socioeconomic status, sex ratio, or intelligence quotient. RESULTS: Regression analyses revealed a negative correlation between age and brain changes, with decreasing gray matter volume and T2 relaxation time with age in multiple brain regions in the type 1 diabetes group. In comparison, the age related decline in the control group was small. Examination of the interaction of group and age confirmed a group difference (type 1 diabetes vs. control) in the relationship between age and brain volume/T2 relaxation time. CONCLUSIONS: We demonstrated an interaction between age and group in predicting brain volumes and T2 relaxation time such that there was a decline in these outcomes in type 1 diabetic participants that was much less evident in control subjects. Findings suggest the neurodevelopmental pathways of youth with type 1 diabetes have diverged from those of their healthy peers by late adolescence and early adulthood but the explanation for this phenomenon remains to be clarified. PMID- 22301126 TI - Efficacy and safety of taspoglutide monotherapy in drug-naive type 2 diabetic patients after 24 weeks of treatment: results of a randomized, double-blind, placebo-controlled phase 3 study (T-emerge 1). AB - OBJECTIVE: To evaluate the efficacy and safety of taspoglutide monotherapy in drug-naive patients with type 2 diabetes inadequately controlled. RESEARCH DESIGN AND METHODS: In this 24-week double-blind, placebo-controlled, multicenter trial, 373 patients with type 2 diabetes naive to antihyperglycemic medication were randomized to weekly subcutaneous taspoglutide 10 or 20 mg or placebo. RESULTS: HbA(1c) reductions from baseline were greater with taspoglutide 10 and 20 mg than placebo (least squares mean [SE] changes: -1.01% [0.07], -1.18% [0.06], and 0.09% [0.07], respectively; both P < 0.0001 vs. placebo). Decreases in bodyweight were greater with taspoglutide 10 mg (-1.45 kg [0.32]) and with 20 mg (-2.25 kg [0.30]) than placebo (-1.23 kg [0.31]; P = 0.61 and P = 0.02 for taspoglutide 10 and 20 mg vs. placebo, respectively). Gastrointestinal adverse events and injection site reactions were more common with taspoglutide than placebo. CONCLUSIONS: In drug-naive patients, once-weekly taspoglutide improved glycemic control, reduced body weight, and was generally well tolerated. PMID- 22301125 TI - Global prevalence and major risk factors of diabetic retinopathy. AB - OBJECTIVE: To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes. RESEARCH DESIGN AND METHODS: A pooled analysis using individual participant data from population-based studies around the world was performed. A systematic literature review was conducted to identify all population-based studies in general populations or individuals with diabetes who had ascertained DR from retinal photographs. Studies provided data for DR end points, including any DR, proliferative DR, diabetic macular edema, and VTDR, and also major systemic risk factors. Pooled prevalence estimates were directly age-standardized to the 2010 World Diabetes Population aged 20-79 years. RESULTS: A total of 35 studies (1980-2008) provided data from 22,896 individuals with diabetes. The overall prevalence was 34.6% (95% CI 34.5-34.8) for any DR, 6.96% (6.87-7.04) for proliferative DR, 6.81% (6.74-6.89) for diabetic macular edema, and 10.2% (10.1 10.3) for VTDR. All DR prevalence end points increased with diabetes duration, hemoglobin A(1c), and blood pressure levels and were higher in people with type 1 compared with type 2 diabetes. CONCLUSIONS: There are approximately 93 million people with DR, 17 million with proliferative DR, 21 million with diabetic macular edema, and 28 million with VTDR worldwide. Longer diabetes duration and poorer glycemic and blood pressure control are strongly associated with DR. These data highlight the substantial worldwide public health burden of DR and the importance of modifiable risk factors in its occurrence. This study is limited by data pooled from studies at different time points, with different methodologies and population characteristics. PMID- 22301127 TI - Integrating an Automated Diabetes Management System into the family management of children with type 1 diabetes: results from a 12-month randomized controlled technology trial. AB - OBJECTIVE: The study objective was to evaluate how the use of a pervasive blood glucose monitoring (BGM) technology relates to glycemic control, report of self care behavior, and emotional response to BGM of children with type 1 diabetes and their parents. RESEARCH DESIGN AND METHODS: Forty-eight children aged less than 12 years (mean 8.8 years) with type 1 diabetes were randomly assigned to one of two study groups, a control group (conventional care without technology) or an experimental group (conventional care with technology), and followed for 12 months. Families in the experimental group were given the Automated Diabetes Management System (ADMS), which automatically collects blood glucose (BG) values and sends to parent(s) a 21-day BG trending report via e-mail each night. Measures of glycemic control (HbA(1c)) were collected at baseline and at quarterly diabetes clinic visits; BGM effect and diabetes self-care behavior measures were obtained at the baseline, 6-month, and 12-month visits. RESULTS: Children in the experimental group had significantly (P = 0.01) lower HbA(1c) at 12 months (7.44 +/- 0.94, -0.35 from baseline) than controls (8.31 +/- 1.24, +0.15 from baseline). Improvement in HbA(1c) was more profound in families using the ADMS more frequently. In addition, in these families, parents showed a significant improvement in BGM effect (P = 0.03) and children became more meticulous in diabetes self-care (P = 0.04). Children in both experimental and control groups experienced no change in their emotional response to BGM. CONCLUSIONS: Using the ADMS 1-3 times/week may help children with type 1 diabetes improve glycemic control and gain diabetes self-management skills, as well as improve the BGM effect of parents. PMID- 22301128 TI - Impaired insulin sensitivity as indexed by the HOMA score is associated with deficits in verbal fluency and temporal lobe gray matter volume in the elderly. AB - OBJECTIVE: Impaired insulin sensitivity is linked to cognitive deficits and reduced brain size. However, it is not yet known whether insulin sensitivity involves regional changes in gray matter volume. Against this background, we examined the association between insulin sensitivity, cognitive performance, and regional gray matter volume in 285 cognitively healthy elderly men and women aged 75 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. RESEARCH DESIGN AND METHODS: Insulin sensitivity was calculated from fasting serum insulin and plasma glucose determinations using the homeostasis model assessment of insulin resistance (HOMA-IR) method. Cognitive performance was examined by a categorical verbal fluency. Participants also underwent a magnetic resonance imaging (MRI) brain scan. Multivariate analysis using linear regression was conducted, controlling for potential confounders (sex, education, serum LDL cholesterol, mean arterial blood pressure, and abdominal visceral fat volume). RESULTS: The HOMA-IR was negatively correlated with verbal fluency performance, brain size, and temporal lobe gray matter volume in regions known to be involved in speech production (Brodmann areas 21 and 22, respectively). No such effects were observed when examining diabetic (n = 55) and cognitively impaired (n = 27) elderly subjects as separate analyses. CONCLUSIONS: These cross-sectional findings suggest that both pharmacologic and lifestyle interventions improving insulin signaling may promote brain health in late life but must be confirmed in patient studies. PMID- 22301129 TI - Mutant flower morphologies in the wind orchid, a novel orchid model species. PMID- 22301130 TI - Constitutive activation of transcription factor OsbZIP46 improves drought tolerance in rice. AB - OsbZIP46 is one member of the third subfamily of bZIP transcription factors in rice (Oryza sativa). It has high sequence similarity to ABA-responsive element binding factor (ABF/AREB) transcription factors ABI5 and OsbZIP23, two transcriptional activators positively regulating stress tolerance in Arabidopsis (Arabidopsis thaliana) and rice, respectively. Expression of OsbZIP46 was strongly induced by drought, heat, hydrogen peroxide, and abscisic acid (ABA) treatment; however, it was not induced by salt and cold stresses. Overexpression of the native OsbZIP46 gene increased ABA sensitivity but had no positive effect on drought resistance. The activation domain of OsbZIP46 was defined by a series of deletions, and a region (domain D) was identified as having a negative effect on the activation. We produced a constitutive active form of OsbZIP46 (OsbZIP46CA1) with a deletion of domain D. Overexpression of OsbZIP46CA1 in rice significantly increased tolerance to drought and osmotic stresses. Gene chip analysis of the two overexpressors (native OsbZIP46 and the constitutive active form OsbZIP46CA1) revealed that a large number of stress-related genes, many of them predicted to be downstream genes of ABF/AREBs, were activated in the OsbZIP46CA1 overexpressor but not (even down-regulated) in the OsbZIP46 overexpressor. OsbZIP46 can interact with homologs of SnRK2 protein kinases that phosphorylate ABFs in Arabidopsis. These results suggest that OsbZIP46 is a positive regulator of ABA signaling and drought stress tolerance of rice depending on its activation. The stress-related genes activated by OsbZIP46CA1 are largely different from those activated by the other rice ABF/AREB homologs (such as OsbZIP23), further implying the value of OsbZIP46CA1 in genetic engineering of drought tolerance. PMID- 22301131 TI - An emerging toolkit for targeted cancer therapies. PMID- 22301132 TI - Translational genomics: the challenge of developing cancer biomarkers. AB - Early detection and definitive treatment of cancer have been shown to decrease death and suffering in epidemiologic and intervention studies. Application of genomic approaches to many malignancies has produced thousands of candidate biomarkers for detection and prognostication, yet very few have become established in clinical practice. Fundamental issues related to tumor heterogeneity, cancer progression, natural history, and biomarker performance have provided challenges to biomarker development. Technical issues in biomarker assay detection limits, specificity, clinical deployment, and regulation have also slowed progress. The recent emergence of biomarkers and molecular imaging strategies for treatment selection and monitoring demonstrates the promise of cancer biomarkers. Organized efforts by interdisciplinary teams will spur progress in cancer diagnostics. PMID- 22301133 TI - Translating cancer 'omics' to improved outcomes. AB - The genomics era has yielded great advances in the understanding of cancer biology. At the same time, the immense complexity of the cancer genome has been revealed, as well as a striking heterogeneity at the whole-genome (or omics) level that exists between even histologically similar tumors. The vast accrual and public availability of multi-omics databases with associated clinical annotation including tumor histology, patient response, and outcome are a rich resource that has the potential to lead to rapid translation of high-throughput omics to improved overall survival. We focus on the unique advantages of a multidimensional approach to genomic analysis in this new high-throughput omics age and discuss the implications of the changing cancer demographic to translational omics research. PMID- 22301134 TI - Paramyxovirus V proteins interact with the RNA Helicase LGP2 to inhibit RIG-I dependent interferon induction. AB - RIG-I and mda-5 are activated by viral RNA and stimulate type I interferon production. Laboratory of genetics and physiology 2 (LGP2) shares homology with RIG-I and mda-5 but lacks the CARD domains required for signaling. The V proteins of paramyxoviruses limit interferon induction by binding mda-5 and preventing its activation; however, they do not bind RIG-I and have not been considered inhibitors of RIG-I signaling. Here we uncover a novel mechanism of RIG-I inhibition in which the V protein of parainfluenzavirus type 5 (PIV5; formerly known as simian virus type 5 [SV5]) interacts with LGP2 and cooperatively inhibits induction by RIG-I ligands. A complex between RIG-I and LGP2 is observed in the presence of PIV5-V, and we propose that this complex is refractory to activation by RIG-I ligands. The V proteins from other paramyxoviruses also bind LGP2 and demonstrate LGP2-dependent inhibition of RIG-I signaling. This is significant, because it demonstrates a general mechanism for the targeting of the RIG-I pathway by paramyxoviruses. PMID- 22301135 TI - HIV-1 capsid-targeting domain of cleavage and polyadenylation specificity factor 6. AB - The antiviral factor CPSF6-358 restricts human immunodeficiency virus type 1 (HIV 1) infection through an interaction with capsid (CA), preventing virus nuclear entry and integration. HIV-1 acquires resistance to CPSF6-358 through an N74D mutation of CA that impairs binding of the antiviral factor. Here we examined the determinants within CPSF6-358 that are necessary for CA-specific interaction. Residues 314 to 322 include amino acids that are essential for CPSF6-358 restriction of HIV-1. Fusion of CPSF6 residues 301 to 358 to rhesus TRIM5alpha is also sufficient to restrict wild-type but not N74D HIV-1. Restriction is lost if CPSF6 residues in the amino acid 314 to 322 interaction motif are mutated. Examination of the CA targeting motif in CPSF6-358 did not reveal evidence of positive selection. Given the sensitivity of different primate lentiviruses to CPSF6-358 and apparent conservation of this interaction, our data suggest that CPSF6-358-mediated targeting of HIV-1 could provide a broadly effective antiviral strategy. PMID- 22301136 TI - Residue Y161 of influenza virus hemagglutinin is involved in viral recognition of sialylated complexes from different hosts. AB - Influenza A virus glycoprotein hemagglutinin (HA) binds to host cell surface sialic acid (SA)-terminated sugars in glycoproteins to initiate viral entry. It is thought that avian influenza viruses preferentially bind to N-acetylneuraminic acid alpha3 (NeuAcalpha3) sugars, while human influenza viruses exhibit a preference for NeuAcalpha6-containing sugars. Thus, species-specific SA(s) is one of the determinants in viral host tropism. The SA binding pocket of the HA1 subunit has been extensively studied, and a number of residues important for receptor binding have been identified. In this study, we examined the potential roles of seven highly conserved HA surface-located amino acid residues in receptor binding and viral entry using an H5 subtype. Among them, mutant Y161A showed cell-type-dependent viral entry without obvious defects in HA protein expression or viral incorporation. This mutant also displayed dramatically different ability in agglutinating different animal erythrocytes. Oligosaccharide binding analysis showed that substituting alanine at Y161 of HA changed the SA binding preference from NeuAc to N-glycolylneuraminic acid (NeuGc). Rescued mutant Y161A viruses demonstrated a 5- to 10-fold growth defect, but they were robust in viral replication and plaque forming ability. Our results demonstrate that Y161 is a critical residue involved in recognition of different SA species. This residue may play a role in determining influenza virus host tropism. PMID- 22301137 TI - A noncanonical mu-1A-binding motif in the N terminus of HIV-1 Nef determines its ability to downregulate major histocompatibility complex class I in T lymphocytes. AB - Downregulation of major histocompatibility complex class I (MHC-I) by HIV-1 Nef protein is indispensable for evasion of protective immunity by HIV-1. Though it has been suggested that the N-terminal region of Nef contributes to the function by associating with a mu-1A subunit of adaptor protein 1, the structural basis of the interaction between Nef and mu-1A remains elusive. We found that a tripartite hydrophobic motif (Trp13/Val16/Met20) in the N terminus of Nef was required for the MHC-I downregulation. Importantly, the motif functioned as a noncanonical mu 1A-binding motif for the interaction with the tyrosine motif-binding site of the mu-1A subunit. Our findings will help understanding of how HIV-1 evades the antiviral immune response by selectively redirecting the cellular protein trafficking system. PMID- 22301138 TI - Herpes simplex virus 1 tegument protein US11 downmodulates the RLR signaling pathway via direct interaction with RIG-I and MDA-5. AB - The interferon (IFN)-mediated antiviral response is a major defense of the host immune system. In order to complete their life cycle, viruses must modulate host IFN-mediated immune responses. Herpes simplex virus 1 (HSV-1) is a large DNA virus containing more than 80 genes, many of which encode proteins that are involved in virus-host interactions and show immune modulatory capabilities. In this study, we demonstrate that the US11 protein, an RNA binding tegument protein of HSV-1, is a novel antagonist of the beta IFN (IFN-beta) pathway. US11 significantly inhibited Sendai virus (SeV)-induced IFN-beta production, and its double-stranded RNA (dsRNA) binding domain was indispensable for this inhibition activity. Additionally, wild-type HSV-1 coinfection showed stronger inhibition than US11 mutant HSV-1 in SeV-induced IFN-beta production. Coimmunoprecipitation analysis demonstrated that the US11 protein in HSV-1-infected cells interacts with endogenous RIG-I and MDA-5 through its C-terminal RNA-binding domain, which was RNA independent. Expression of US11 in both transfected and HSV-1-infected cells interferes with the interaction between MAVS and RIG-I or MDA-5. Finally, US11 dampens SeV-mediated IRF3 activation. Taken together, the combined data indicate that HSV-1 US11 binds to RIG-I and MDA-5 and inhibits their downstream signaling pathway, preventing the production of IFN-beta, which may contribute to the pathogenesis of HSV-1 infection. PMID- 22301139 TI - Interleukin-27 inhibits vaccine-enhanced pulmonary disease following respiratory syncytial virus infection by regulating cellular memory responses. AB - Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract disease in young children. In the 1960s, infants vaccinated with formalin-inactivated RSV developed a more severe disease characterized by excessive inflammatory immunopathology in lungs upon natural RSV infection. The fear of causing the vaccine-enhanced disease (VED) is an important obstacle for development of safe and effective RSV vaccines. The recombinant vaccine candidate G1F/M2 immunization also led to VED. It has been proved that cellular memory induced by RSV vaccines contributed to VED. Interleukin-27 (IL-27) and IL-23 regulate Th1, Th17, and/or Th2 cellular immune responses. In this study, mice coimmunized with pcDNA3-IL-27 and G1F/M2 were fully protected and, importantly, did not develop vaccine-enhanced inflammatory responses and immunopathology in lungs after RSV challenge, which was correlated with moderate Th1-, suppressed Th2-, and Th17-like memory responses activated by RSV. In contrast, G1F/M2- or pcDNA3-IL-23+G1F/M2-immunized mice, in which robust Th2- and Th17-like memory responses were induced, developed enhanced pulmonary inflammation and severe immunopathology. Mice coimmunized with G1F/M2 and the two cytokine plasmids exhibited mild inflammatory responses as well as remarkable Th1-, suppressed Th2 , and Th17-like memory responses. These results suggested that Th1-, Th2-, and Th17-like memory responses and, in particular, excessive Th2- and Th17-like memory responses were closely associated with VED; IL-27 may inhibit VED following respiratory syncytial virus infection by regulating cellular memory responses. PMID- 22301140 TI - The genome sequence of the emerging common midwife toad virus identifies an evolutionary intermediate within ranaviruses. AB - Worldwide amphibian population declines have been ascribed to global warming, increasing pollution levels, and other factors directly related to human activities. These factors may additionally be favoring the emergence of novel pathogens. In this report, we have determined the complete genome sequence of the emerging common midwife toad ranavirus (CMTV), which has caused fatal disease in several amphibian species across Europe. Phylogenetic and gene content analyses of the first complete genomic sequence from a ranavirus isolated in Europe show that CMTV is an amphibian-like ranavirus (ALRV). However, the CMTV genome structure is novel and represents an intermediate evolutionary stage between the two previously described ALRV groups. We find that CMTV clusters with several other ranaviruses isolated from different hosts and locations which might also be included in this novel ranavirus group. This work sheds light on the phylogenetic relationships within this complex group of emerging, disease-causing viruses. PMID- 22301141 TI - HIV-1 virus-like particles bearing pure env trimers expose neutralizing epitopes but occlude nonneutralizing epitopes. AB - Hypothetically, since native HIV-1 Env trimers are exclusively recognized by neutralizing antibodies, they might induce the neutralizing antibodies in a vaccine setting. This idea has not been evaluated due to the difficulty of separating trimers from nonfunctional Env (uncleaved gp160 and gp41 stumps). The latter are immunodominant and induce nonneutralizing antibodies. We previously showed that nonfunctional Env can be selectively cleared from virus-like particle (VLP) surfaces by enzyme digests (E. T. Crooks, T. Tong(,) K. Osawa, and J. M. Binley, J.Virol. 85:5825, 2011). Here, we investigated the effects of these digests on the antigenicity of VLPs and their sensitivity to neutralization. Before digestion, WT VLPs (bearing wild-type Env) and UNC VLPs (bearing uncleaved gp160) were recognized by various Env-specific monoclonal antibodies (MAbs), irrespective of their neutralizing activity, a result which is consistent with the presence of nonfunctional Env. After digestion, only neutralizing MAbs recognized WT VLPs, consistent with selective removal of nonfunctional Env (i.e., "trimer VLPs"). Digests eliminated the binding of all MAbs to UNC VLPs, again consistent with removal of nonfunctional Env. An exception was MAb 2F5, which weakly bound to digested UNC VLPs and bald VLPs (bearing no Env), perhaps due to lipid cross-reactivity. Trimer VLPs were infectious, and their neutralization sensitivity was largely comparable to that of undigested WT VLPs. However, they were ~100-fold more sensitive to the MAbs 4E10 and Z13e1, suggesting increased exposure of the gp41 base. Importantly, a scatterplot analysis revealed a strong correlation between MAb binding and neutralization of trimer VLPs. This suggests that trimer VLPs bear essentially pure native trimer that should allow its unfettered evaluation in a vaccine setting. PMID- 22301142 TI - Disulfide linkages mediating nucleocapsid protein dimerization are not required for porcine arterivirus infectivity. AB - The nucleocapsid (N) proteins of the North American (type II) and European (type I) genotypes of porcine reproductive and respiratory syndrome virus (PRRSV) share only approximately 60% genetic identity, and the functionality of N in both genotypes, especially its role in virion assembly, is still poorly understood. In this study, we demonstrated that the ORF7 3' untranslated region or ORF7 of type I is functional in the type II PRRSV background. Based on these results, we postulated that the cysteine at position 90 (Cys90) of the type II N protein, which corresponds to an alanine in the type I protein, is nonessential for virus infectivity. The replacement of Cys90 with alanine confirmed this hypothesis. We then hypothesized that all of the cysteines in the N protein could be replaced by alanines. Mutational analysis revealed that, in contradiction to previously reported findings, the replacement of all of the cysteines, either singly or in combination, did not impair the growth of either type II or type I PRRSV. Treatment with the alkylating agent N-ethylmaleimide inhibited cysteine-mediated N dimerization in living cells but not in released virions. Additionally, bimolecular fluorescence complementation assays revealed noncovalent interactions in living cells among the N and C termini and between the N-terminal and C terminal regions of the N proteins of both genotypes of PRRSV. These results demonstrate that the disulfide linkages mediating the N dimerization are not required for PRRSV viability and help to promote our understanding of the mechanism underlying arterivirus particle assembly. PMID- 22301143 TI - Virus-activated interferon regulatory factor 7 upregulates expression of the interferon-regulated BST2 gene independently of interferon signaling. AB - BST-2/tetherin is an interferon (IFN)-inducible host restriction factor that inhibits the release of many enveloped viruses and functions as a negative feedback regulator of IFN production by plasmacytoid dendritic cells. Currently, mechanisms underlying BST2 transcriptional regulation by type I IFN remain largely unknown. Here, we demonstrate that the BST2 promoter is a secondary target of the IFN cascade and show that a single IRF binding site is sufficient to render this promoter responsive to IFN-alpha. Interestingly, expression of IRF 1 or virus-activated forms of IRF-3 and IRF-7 stimulated the BST2 promoter even under conditions where type I IFN signaling was inhibited. Indeed, vesicular stomatitis virus could directly upregulate BST-2 during infection of mouse embryonic fibroblasts through a process that required IRF-7 but was independent from the type I IFN cascade; however, in order to achieve optimal BST-2 induction, the type I IFN cascade needed to be engaged through activation of IRF 3. Furthermore, using human peripheral blood mononuclear cells, we show that BST 2 upregulation is part of an early intrinsic immune response since TLR8 and TLR3 agonists, known to trigger pathways that mediate activation of IRF proteins, could upregulate BST-2 prior to engagement of the type I IFN pathway. Collectively, our findings reveal that BST2 is activated by the same signals that trigger type I IFN production, outlining a regulatory mechanism ensuring that production of type I IFN and expression of a host restriction factor involved in the IFN negative-feedback loop are closely coordinated. PMID- 22301144 TI - A replication-incompetent PB2-knockout influenza A virus vaccine vector. AB - Vaccination is the primary form of protection from influenza virus infection. We recently developed a replication-incompetent PB2-knockout (PB2-KO) influenza virus that possesses a reporter gene (the green fluorescent protein gene) in the coding region of the PB2 segment. This virus replicated to high titers in PB2 expressing, but not unmodified, cells, suggesting its potential safety and feasibility as a vaccine. Here, we tested its efficacy in a murine model. The levels of IgG and IgA antibodies against influenza virus in sera, nasal washes, and bronchoalveolar lavage fluids of mice immunized with the PB2-KO virus were higher than those induced by a conventional inactivated vaccine. All PB2-KO virus immunized mice survived challenges with lethal doses of influenza virus. Moreover, importantly, mice immunized with the PB2-KO virus produced antibodies against the reporter protein, suggesting that the PB2-KO virus has potential as a multivalent vaccine to combat infection with not only influenza virus but also other pathogens. PMID- 22301145 TI - Human immunodeficiency virus type 1 capsid mutation N74D alters cyclophilin A dependence and impairs macrophage infection. AB - The antiviral factor CPSF6-358 interferes with the nuclear entry of human immunodeficiency virus type 1 (HIV-1). HIV-1 acquires resistance to CPSF6-358 through the N74D mutation of the capsid (CA), which alters its nuclear entry pathway. Here we show that compared to wild-type (WT) HIV-1, N74D HIV-1 is more sensitive to cyclosporine, has increased sensitivity to nevirapine, and is impaired in macrophage infection prior to reverse transcription. These phenotypes suggest a difference in the N74D reverse transcription complex that manifests early after infection and prior to interaction with the nuclear pore. Overall, our data indicate that N74D HIV-1 replication in transformed cells requires cyclophilin A but is dependent on other interactions in macrophages. PMID- 22301146 TI - Mouse norovirus 1 utilizes the cytoskeleton network to establish localization of the replication complex proximal to the microtubule organizing center. AB - Human noroviruses (family Caliciviridae) are the leading cause of nonbacterial gastroenteritis worldwide. Although Human noroviruses are significant enteric pathogens, there exists no reliable vaccine or therapy to treat infected individuals. To date, attempts to cultivate Human noroviruses within the laboratory have met with little success; however, the related murine norovirus mouse norovirus 1 (MNV-1) has provided an ideal model system to study norovirus replication due to the ease with which the virus is cultivated and the ability to infect a small animal model with this virus. Previously we have identified the association between MNV-1 and components of the host secretory pathway and proposed a role for the viral open reading frame 1 proteins in the replication cycle. Here we describe for the first time a role for cytoskeletal components in early MNV-1 replication events. We show that the MNV-1 utilizes microtubules to position the replication complex adjacent to the microtubule organizing center. Chemical disruption of the microtubule network disperses the sites of MNV-1 replication throughout the cell and impairs production of viral protein and infectious virus. Furthermore, we demonstrate the ability of MNV-1 to redistribute acetylated tubulin to the replication complex and that this association is potentially mediated via the MNV-1 major structural protein, VP1. Transient expression of MNV-1 VP1 exhibited extensive colocalization with both alpha-tubulin and acetylated tubulin and was observed to alter the distribution of acetylated tubulin in transfected cells. This study highlights the role of the cytoskeleton in early virus replication events and demonstrates the importance of this interaction in establishing the intracellular location of MNV-1 replication complexes. PMID- 22301147 TI - Induced pluripotent stem cell clones reprogrammed via recombinant adeno associated virus-mediated transduction contain integrated vector sequences. AB - Fibroblasts can be reprogrammed into induced pluripotent stem cells (iPSC) by ectopic expression of key transcription factors. Current methods for the generation of integration-free iPSC are limited by the low efficiency of iPSC generation and by challenges in reprogramming methodology. Recombinant adeno associated virus (rAAV) is a potent gene delivery vehicle capable of efficient transduction of transgenic DNA into cells. rAAV stays mainly as an episome in nondividing cells, and the extent of integration is still poorly defined for various replicating cells. In this study, we aimed to induce iPSC from mouse and human fibroblasts by using rAAV vector-mediated transient delivery of reprogramming factors. We succeeded in deriving induced pluripotent stem cells from mouse but not human fibroblasts. Unexpectedly, the rAAV vector-mediated reprogramming led to frequent genomic integration of vector sequences during the reprogramming process, independent of the amount of virus used, and to persistent expression of reprogramming factors in generated iPSC clones. It thus appears that rAAV vectors are not compatible with the derivation of integration-free iPSC. PMID- 22301148 TI - Characterization of the 55-residue protein encoded by the 9S E1A mRNA of species C adenovirus. AB - Early region 1A (E1A) of human adenovirus (HAdV) has been the focus of over 30 years of investigation and is required for the oncogenic capacity of HAdV in rodents. Alternative splicing of the E1A transcript generates mRNAs encoding multiple E1A proteins. The 55-residue (55R) E1A protein, which is encoded by the 9S mRNA, is particularly interesting due to the unique properties it displays relative to all other E1A isoforms. 55R E1A does not contain any of the conserved regions (CRs) present in the other E1A isoforms. The C-terminal region of the 55R E1A protein contains a unique sequence compared to all other E1A isoforms, which results from a frameshift generated by alternative splicing. The 55R E1A protein is thought to be produced preferentially at the late stages of infection. Here we report the first study to directly investigate the function of the species C HAdV 55R E1A protein during infection. Polyclonal rabbit antibodies (Abs) have been generated that are capable of immunoprecipitating HAdV-2 55R E1A. These Abs can also detect HAdV-2 55R E1A by immunoblotting and indirect immunofluorescence assay. These studies indicate that 55R E1A is expressed late and is localized to the cytoplasm and to the nucleus. 55R E1A was able to activate the expression of viral genes during infection and could also promote productive replication of species C HAdV. 55R E1A was also found to interact with the S8 component of the proteasome, and knockdown of S8 was detrimental to viral replication dependent on 55R E1A. PMID- 22301149 TI - Transmission of influenza B viruses in the guinea pig. AB - Epidemic influenza is typically caused by infection with viruses of the A and B types and can result in substantial morbidity and mortality during a given season. Here we demonstrate that influenza B viruses can replicate in the upper respiratory tract of the guinea pig and that viruses of the two main lineages can be transmitted with 100% efficiency between inoculated and naive animals in both contact and noncontact models. Our results also indicate that, like in the case for influenza A virus, transmission of influenza B viruses is enhanced at colder temperatures, providing an explanation for the seasonality of influenza epidemics in temperate climates. We therefore present, for the first time, a small animal model with which to study the underlying mechanisms of influenza B virus transmission. PMID- 22301150 TI - Two distinct broadly neutralizing antibody specificities of different clonal lineages in a single HIV-1-infected donor: implications for vaccine design. AB - Plasma from a small subset of subjects chronically infected with HIV-1 shows remarkable magnitude and breadth of neutralizing activity. From one of these individuals (CH0219), we isolated two broadly neutralizing antibodies (bnAbs), CH01 and VRC-CH31, from two clonal lineages of memory B cells with distinct specificities (variable loop 1 and 2 [V1V2] conformational specificity and CD4 binding site specificity, respectively) that recapitulate 95% of CH0219 serum neutralization breadth. These data provide proof of concept for an HIV-1 vaccine that aims to elicit bnAbs of multiple specificities. PMID- 22301151 TI - Passively transmitted gp41 antibodies in babies born from HIV-1 subtype C seropositive women: correlation between fine specificity and protection. AB - HIV-exposed, uninfected (EUN) babies born to HIV-infected mothers are examples of natural resistance to HIV infection. In this study, we evaluated the titer and neutralizing potential of gp41-specific maternal antibodies and their correlation with HIV transmission in HIV-infected mother-child pairs. Specific gp41-binding and -neutralizing antibodies were determined in a cohort of 74 first-time mother child pairs, of whom 40 mothers were infected with HIV subtype C. Within the infected mother cohort, 16 babies were born infected and 24 were PCR negative and uninfected at birth (i.e., exposed but uninfected). Thirty-four HIV-uninfected and HIV-unexposed mother-child pairs were included as controls. All HIV-positive mothers and their newborns showed high IgG titers to linear epitopes within the HR1 region and to the membrane-proximal (MPER) domain of gp41; most sera also recognized the disulfide loop immunodominant epitope (IDE). Antibody titers to the gp41 epitopes were significantly lower in nontransmitting mothers (P < 0.01) and in the EUN babies (P < 0.005) than in HIV-positive mother-child pairs. Three domains of gp41, HR1, IDE, and MPER, elicited antibodies that were effectively transmitted to EUN babies. Moreover, in EUN babies, epitopes overlapping the 2F5 epitope (ELDKWAS), but not the 4E10 epitope, were neutralization targets in two out of four viruses tested. Our findings highlight important epitopes in gp41 that appear to be associated with exposure without infection and would be important to consider for vaccine design. PMID- 22301152 TI - The human immunodeficiency virus type 1 Nef and Vpu proteins downregulate the natural killer cell-activating ligand PVR. AB - The human immunodeficiency virus type 1 (HIV-1) evades the immune responses of natural killer (NK) cells through mechanisms that have been partially deciphered. Here we show that in HIV-1-infected T lymphocytes, the early viral Nef protein downmodulates PVR (CD155, Necl-5), a ligand for the activating receptor DNAM-1 (CD226) expressed by all NK cells, CD8(+) T cells, and other cell types. This novel Nef activity is conserved by Nef proteins of laboratory HIV-1 strains (NL4 3, SF2) and of a patient-derived virus, but it is not maintained by HIV-2. Nef uses the same motifs to downregulate PVR and HLA-I molecules, likely by the same mechanisms. Indeed, as previously demonstrated for HLA-I, Nef reduces the total amounts of cell-associated PVR. Optimal downregulation of cell surface PVR by Nef also requires the presence of the late viral factor Vpu. In line with PVR reduction, the NK cell-mediated lysis of T cells infected by a wild-type but not Nef-deficient virus is virtually abrogated upon blocking of both DNAM-1 and another activating receptor, NKG2D, previously shown to mediate killing of HIV infected cells. Together, these data demonstrate that the PVR downmodulation by Nef and Vpu is a strategy evolved by HIV-1 to prevent NK cell-mediated lysis of infected cells. The PVR downregulation reported here has the potential to affect the immune responses of other DNAM-1-positive cells besides NK cells and to alter multiple PVR-mediated cellular processes, such as adhesion and migration, and may thus greatly influence HIV-1 pathogenesis. PMID- 22301153 TI - The coronavirus endoribonuclease Nsp15 interacts with retinoblastoma tumor suppressor protein. AB - Coronaviruses encode an endoribonuclease, Nsp15, which has a poorly defined role in infection. Sequence analysis revealed a retinoblastoma protein-binding motif (LXCXE/D) in the majority of the Nsp15 of the severe acute respiratory syndrome coronavirus (SARS-CoV) and its orthologs in the alpha and beta coronaviruses. The endoribonuclease activity of the SARS-CoV Nsp15 (sNsp15) was stimulated by retinoblastoma protein (pRb) in vitro, and the two proteins can be coimmunoprecipitated from cellular extracts. Mutations in the pRb-binding motif rendered sNsp15 to be differentially modified by ubiquitin in cells, and cytotoxicity was observed upon its expression. Expression of the sNsp15 in cells resulted in an increased abundance of pRb in the cytoplasm, decreased overall levels of pRb, an increased proportion of cells in the S phase of the cell cycle, and an enhanced expression from a promoter normally repressed by pRb. The endoribonuclease activity of the mouse hepatitis virus (MHV) A59 Nsp15 was also increased by pRb in vitro, and an MHV with mutations in the LXCXE/D-motif, named vLC, exhibited a smaller plaque diameter and reduced the virus titer by ~1 log. Overexpression of pRb delayed the viral protein production by wild-type MHV but not by vLC. This study reveals that pRb and its interaction with Nsp15 can affect coronavirus infection and adds coronaviruses to a small but growing family of RNA viruses that encode a protein to interact with pRb. PMID- 22301154 TI - Amino acid substitutions at positions 122 and 145 of hepatitis B virus surface antigen (HBsAg) determine the antigenicity and immunogenicity of HBsAg and influence in vivo HBsAg clearance. AB - A variety of amino acid substitutions, such as K122I and G145R, have been identified around or within the a determinant of hepatitis B surface antigen (HBsAg), impair HBsAg secretion and antibody binding, and may be responsible for immune escape in patients. In this study, we examined how different substitutions at amino acid positions 122 and 145 of HBsAg influence HBsAg expression, secretion, and recognition by anti-HBs antibodies. The results showed that the hydrophobicity, the presence of the phenyl group, and the charges in the side chain of the amino acid residues at position 145 reduced HBsAg secretion and impaired reactivity with anti-HBs antibodies. Only the substitution K122I at position 122 affected HBsAg secretion and recognition by anti-HBs antibodies. Genetic immunization in mice demonstrated that the priming of anti-HBs antibody response was strongly impaired by the substitutions K122I, G145R, and others, like G145I, G145W, and G145E. Mice preimmunized with wild-type HBsAg (wtHBsAg) or variant HBsAg (vtHBsAg) were challenged by hydrodynamic injection (HI) with a replication-competent hepatitis B virus (HBV) clone. HBsAg persisted in peripheral blood for at least 3 days after HI in mice preimmunized with vtHBsAg but was undetectable in mice preimmunized with wtHBsAg, indicating that vtHBsAgs fail to induce proper immune responses for efficient HBsAg clearance. In conclusion, the biochemical properties of amino acid residues at positions 122 and 145 of HBsAg have a major effect on antigenicity and immunogenicity. In addition, the presence of proper anti-HBs antibodies is indispensable for the neutralization and clearance of HBsAg during HBV infection. PMID- 22301155 TI - Bovine type III interferon significantly delays and reduces the severity of foot and-mouth disease in cattle. AB - Interferons (IFNs) are the first line of defense against viral infections. Although type I and II IFNs have proven effective to inhibit foot-and-mouth disease virus (FMDV) replication in swine, a similar approach had only limited efficacy in cattle. Recently, a new family of IFNs, type III IFN or IFN-lambda, has been identified in human, mouse, chicken, and swine. We have identified bovine IFN-lambda3 (boIFN-lambda3), also known as interleukin 28B (IL-28B), and demonstrated that expression of this molecule using a recombinant replication defective human adenovirus type 5 (Ad5) vector, Ad5-boIFN-lambda3, exhibited antiviral activity against FMDV in bovine cell culture. Furthermore, inoculation of cattle with Ad5-boIFN-lambda3 induced systemic antiviral activity and upregulation of IFN-stimulated gene expression in the upper respiratory airways and skin. In the present study, we demonstrated that disease could be delayed for at least 6 days when cattle were inoculated with Ad5-boIFN-lambda3 and challenged 24 h later by intradermolingual inoculation with FMDV. Furthermore, the delay in the appearance of disease was significantly prolonged when treated cattle were challenged by aerosolization of FMDV, using a method that resembles the natural route of infection. No clinical signs of FMD, viremia, or viral shedding in nasal swabs was found in the Ad5-boIFN-lambda3-treated animals for at least 9 days postchallenge. Our results indicate that boIFN-lambda3 plays a critical role in the innate immune response of cattle against FMDV. To this end, this work represents the most successful biotherapeutic strategy so far tested to control FMDV in cattle. PMID- 22301156 TI - Overreliance on the hexon gene, leading to misclassification of human adenoviruses. AB - The genome of human adenovirus (HAdV) D30 was sequenced in depth. Sequence assembly and analysis revealed two distinct viral sequences with identical hexon genes, which were the same as the one previously reported for HAdV-D30. However, one of the two viruses was found to be a recombinant of HAdV-D29. Exclusive reliance on serum neutralization can lead to mischaracterization of adenoviruses and miss coinfections. Whole-genome sequencing remains the gold standard for proper classification of HAdVs. PMID- 22301157 TI - Annexin A2 is involved in the formation of hepatitis C virus replication complex on the lipid raft. AB - The hepatitis C virus (HCV) RNA replicates in hepatic cells by forming a replication complex on the lipid raft (detergent-resistant membrane [DRM]). Replication complex formation requires various viral nonstructural (NS) proteins as well as host cellular proteins. In our previous study (C. K. Lai, K. S. Jeng, K. Machida, and M. M. Lai, J. Virol. 82:8838-8848, 2008), we found that a cellular protein, annexin A2 (Anxa2), interacts with NS3/NS4A. Since NS3/NS4A is a membranous protein and Anxa2 is known as a lipid raft-associated scaffold protein, we postulate that Anxa2 helps in the formation of the HCV replication complex on the lipid raft. Further studies showed that Anxa2 was localized at the HCV-induced membranous web and interacted with NS4B, NS5A, and NS5B and colocalized with them in the perinuclear region. The silencing of Anxa2 decreased the formation of membranous web-like structures and viral RNA replication. Subcellular fractionation and bimolecular fluorescence complementation analysis revealed that Anxa2 was partially associated with HCV at the lipid raft enriched with phosphatidylinositol-4-phosphate (PI4P) and caveolin-2. Further, the overexpression of Anxa2 in HCV-nonsusceptible HEK293 cells caused the enrichment of HCV NS proteins in the DRM fraction and increased the colony-forming ability of the HCV replicon. Since Anxa2 is known to induce the formation of the lipid raft microdomain, we propose that Anxa2 recruits HCV NS proteins and enriches them on the lipid raft to form the HCV replication complex. PMID- 22301158 TI - Quantification and analysis of thymidine kinase expression from acyclovir resistant G-string insertion and deletion mutants in herpes simplex virus infected cells. AB - To be clinically relevant, drug-resistant mutants must both evade drug action and retain pathogenicity. Many acyclovir-resistant herpes simplex virus mutants from clinical isolates have one or two base insertions (G8 and G9) or one base deletion (G6) in a homopolymeric run of seven guanines (G string) in the gene encoding thymidine kinase (TK). Nevertheless, G8 and G9 mutants express detectable TK activity and can reactivate from latency in mice, a pathogenicity marker. On the basis of studies using cell-free systems, ribosomal frameshifting can explain this ability to express TK. To investigate frameshifting in infected cells, we constructed viruses that express epitope-tagged versions of wild-type and mutant TKs. We measured TK activity by plaque autoradiography and expression of frameshifted and unframeshifted TK polypeptides using a very sensitive immunoprecipitation-Western blotting method. The G6 mutant expressed ~0.01% of wild-type levels of TK polypeptide. For the G9 mutant, consistent with previous results, much TK expression could be ascribed to reversion. For the G8 mutant, from these assays and pulse-labeling studies, we determined the ratio of synthesis of frameshifted to unframeshifted polypeptides to be 1:100. The effects of stop codons before or after the G string argue that frameshifting can initiate within the first six guanines. However, frameshifting efficiency was altered by stop codons downstream of the string in the 0 frame. The G8 mutant expressed only 0.1% of the wild-type level of full-length TK, considerably lower than estimated previously. Thus, remarkably low levels of TK are sufficient for reactivation from latency in mice. PMID- 22301159 TI - The cellular antiviral protein APOBEC3G interacts with HIV-1 reverse transcriptase and inhibits its function during viral replication. AB - The cytidine deaminase APOBEC3G (A3G) exerts a multifaceted antiviral effect against HIV-1 infection. First, A3G was shown to be able to terminate HIV infection by deaminating the cytosine residues to uracil in the minus strand of the viral DNA during reverse transcription. Also, a number of studies have indicated that A3G inhibits HIV-1 reverse transcription by a non-editing-mediated mechanism. However, the mechanism by which A3G directly disrupts HIV-1 reverse transcription is not fully understood. In the present study, by using a cell based coimmunoprecipitation (Co-IP) assay, we detected the direct interaction between A3G and HIV-1 reverse transcriptase (RT) in produced viruses and in the cotransfected cells. The data also suggested that their interaction did not require viral genomic RNA bridging or other viral proteins. Additionally, a deletion analysis showed that the RT-binding region in A3G was located between amino acids 65 and 132. Overexpression of the RT-binding polypeptide A3G(65-132) was able to disrupt the interaction between wild-type A3G and RT, which consequently attenuated the anti-HIV effect of A3G on reverse transcription. Overall, this paper provides evidence for the physical and functional interaction between A3G and HIV-1 RT and demonstrates that this interaction plays an important role in the action of A3G against HIV-1 reverse transcription. PMID- 22301160 TI - Fucoidan, a sulfated polysaccharide from brown algae, improves cognitive impairment induced by infusion of Abeta peptide in rats. AB - Fucoidan is a complex sulfated polysaccharide, derived from marine brown seaweed. In the present study, we investigated the effects of fucoidan on improving learning and memory impairment in rats induced by infusion of Abeta (1-40), and its possible mechanisms. The results indicated that fucoidan could ameliorate Abeta-induced learning and memory impairment in animal behavioral tests. Furthermore, fucoidan reversed the decreased activity of choline acetyl transferase (ChAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and content of acetylcholine (Ach), as well as the increased activity of acetylcholine esterase (AchE) and content of malondialdehyde (MDA) in hippocampal tissue of Abeta-injected rats. Moreover, these were accompanied by an increase of Bcl-2/Bax ratio and a decrease of caspase-3 activity. These results suggested that fucoidan could ameliorate the learning and memory abilities in Abeta-induced AD rats, and the mechanisms appeared to be due to regulating the cholinergic system, reducing oxidative stress and inhibiting the cell apoptosis. PMID- 22301161 TI - Let-7 g is involved in doxorubicin induced myocardial injury. AB - OBJECTIVES: To investigate whether let-7 g (miRNA) was involved in doxorubicin induced cardiotoxicity. METHODS: Rats were treated with doxorubicin at increasing doses (0mg/kg, 6 mg/kg, 12 mg/kg, 18 mg/kg). Heart rate, pulse pressure and plasma cardiac troponin T concentrations were measured. Primary cultured myocardial cells were incubated with DOX at increasing concentrations (0 MUmol/l, 0.004 MUmol/l, 0.02 MUmol/l, 0.1 MUmol/l, 0.5 MUmol/l) for 24h. Cellular viability and the beat frequency were measured. For both rats and cultured cells, miRNA content was measured by real-time reverse-transcription PCR. RESULTS: All DOX-treated rats had a decrease in heart rate, an increase in pulse pressure compared with control group after injections (p<0.05). Concentration of cTnT was increased significantly in 18 mg/kg group. Content of let-7 g decreased significantly (p<0.05) in 18 mg/kg group in vivo and all the doxorubicin treated group in vitro. CONCLUSIONS: The down regulation of let-7 g in the myocardial injury model suggests that let-7 g may play an important role in the development of cardiac disease. PMID- 22301162 TI - Microcystin-LR causes cytotoxicity effects in rat testicular Sertoli cells. AB - Microcystins (MCs) are produced by cyanobacteria. The most toxic and widely distributed MC is microcystin-LR (MC-LR). The aim of this study was to investigate whether exposure to MC-LR could induce oxidative stress, leading the further toxicity effects on Sertoli cells in vitro. Sertoli cells obtained from rats were cultured with a medium containing 0, 0.5, 5, 50 or 500 nM/l MC-LR. We examined the decrease of mitochondrial membrane potential (MMP), the increase of reactive oxygen species (ROS) production, the increase of lipid peroxidation and decrease of superoxide dismutase (SOD) activity in Sertoli cells after treatment with MC-LR in vitro, and higher expression of caspase-9 and caspase-3, the increase of apoptosis rate. Therefore, we deduced that direct exposure to microcystin-LR could induce oxidative stress generation in Sertoli cells, and subsequently depressed cellular viability and caused cells to undergo apoptosis, resulting in the reproductive toxicity in male rats. PMID- 22301163 TI - The influence of Cd2+, Hg2+ and Pb2+ on taxifolin binding to bovine serum albumin by spectroscopic methods: with the viewpoint of toxic ions/drug interference. AB - The effect of heavy metal ions, Cd(2+), Hg(2+) and Pb(2+) on taxifolin binding to bovine serum albumin (BSA) has been investigated by spectroscopic methods. The results indicated that the presence of heavy metal ions significantly affected the binding modes and binding affinities of taxifolin to BSA, and the effects depended on the type of heavy metal ions. One binding mode was found for taxifolin with and without Cd(2+), while two binding modes-a weaker one at low concentration and a stronger one at high concentration-were found for taxifolin in the presence of Hg(2+) and Pb(2+). Cd(2+) decreased the binding affinity of taxifolin for BSA by 7.3%; however, Hg(2+) increased the binding affinity of taxifolin for BSA by 13.3% in lower concentration and 33.3% in higher concentration. Pb(2+) decreased the binding affinity of taxifolin for BSA by 28.4% in lower concentration, and increased the binding affinity of taxifolin for BSA by 20.6% in higher concentration. The decreased binding affinity of taxifolin for BSA in the presence of Cd(2+) was mainly because of the existence of competitive binding between taxifolin and Cd(2+). However, the conformational change of BSA may the main reason for the changed binding affinity and binding distance of taxifolin for BSA in the presence of Hg(2+) and Pb(2+). PMID- 22301164 TI - Effect of chronic exposure to simazine on oxidative stress and antioxidant response in common carp (Cyprinus carpio L.). AB - We investigated the chronic effect of simazine, an s-triazine herbicide commonly present in aquatic environments, on the antioxidant system and oxidative stress indices in common carp (Cyprinus carpio L.). Fish were exposed to sub-lethal concentrations of 0.06 MUg l(-1) (environmental concentration in Czech rivers), 2 mg l(-1), and 4 mg l(-1) for 14, 28 and 60 days. Indices of oxidative stress [reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS)], and antioxidant parameters [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH)] in fish brain, gill, muscle, liver, and intestine were measured. Chronic exposure to simazine showed the impact of the increased production of ROS leading to oxidative damage to lipids, proteins, and inhibition of antioxidant capacity. Activity of the antioxidant enzymes SOD, CAT, GPx and GSH in groups with high concentrations (2 mg l(-1), 4 mg l(-1)) increased at 14 and 28 days, but decreased after 60 days exposure (p<0.01) as compared with the control group. Changes in enzyme activity were mainly in the liver, but also in gills and brain. Prolonged exposure to simazine resulted in excess ROS formation finally resulting in oxidative damage to cell lipids and proteins and also inhibited antioxidant capacities in common carp tissue. PMID- 22301165 TI - Does non-steroidal anti-inflammatory (NSAID) ibuprofen induce antioxidant stress and endocrine disruption in mussel Mytilus galloprovincialis? AB - Ibuprofen (IBU) is one of the most sold over-the-counter non-steroidal anti inflammatory drugs (NSAID) and widely detected in the aquatic ecosystems. Nevertheless, the information regarding IBU effects in biota is still sparse. The goal of this study was to assess IBU potential effect as oxidative stress and endocrine disruption inducer in mussel Mytilus galloprovincialis applying a battery of biomarkers. Over two weeks of exposure to IBU (250 ngL(-1)), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), phase II glutathione S-transferase (GST) activities and lipid peroxidation (LPO) levels were determined in the digestive gland and alkali-labile phosphates (ALP) were carried out in sex-differentiated mussels' gonads. The results confirm a transitory induction of antioxidant activities responses concomitant to lipid peroxide formation outline and an increase of ALP levels over time, particularly in exposed males which may lead to mussels' reproductive fitness impairment highlighting a higher impact of IBU as an endocrine disruptor than as a short term reactive oxygen species (ROS)-generator. PMID- 22301166 TI - Eco-toxicological effect of carbamazepine on Scenedesmus obliquus and Chlorella pyrenoidosa. AB - The acute and chronic toxicological effects of carbamazepine (CBZ) on Scenedesmus obliquus and Chlorella pyrenoidosa were explored for the first time in this study. The results showed that CBZ could significantly inhibit the growth of the two algae in almost all treatment groups. EC(50) values indicated that, CBZ had a relatively limited acute toxic effect (0-144 h) on S. obliquus and C. pyrenoidosa, while, chronic tests (5-30 d) displayed higher toxicity. Chlorophyll a syntheses were nearly all inhibited by CBZ exposure. However, superoxide dismutase (SOD) and catalase (CAT) activities in acute tests of both algae were markedly promoted. According to the results, Chlorophyll a content and CAT activity of S. obliquus were more sensitive to CBZ than that of C. pyrenoidosa. While for SOD, quite to the contrary, C. pyrenoidosa was more vulnerable. We obtained a similar result in chronic tests. This research furthers our understanding of CBZ toxicity to aquatic organisms. PMID- 22301167 TI - Astrocyte mediated protection of fetal cerebral cortical neurons from rotenone and paraquat. AB - Primary cultures of fetal rat cortical neurons and astrocytes were used to test the hypothesis that astrocyte-mediated control of neuronal glutathione (GSH) is a potent factor in neuroprotection against rotenone and paraquat. In neurons, rotenone (0.025-1 MUM) for 4 and 24 h decreased viability as did paraquat (2-100 MUM). Rotenone (30 nM) decreased neuronal viability and GSH by 24% and 30%, while ROS were increased by 56%. Paraquat (30 MUM) decreased neuronal viability and GSH by 36% and 70%, while ROS were increased by 23%. When neurons were co-cultured with astrocytes, their GSH increased 1.5 fold and 5 fold at 12 and 24 h. Co culturing with astrocytes blocked neuronal death and damage by rotenone and paraquat. Astrocyte-mediated neuroprotection was dependent on the activity of components of the gamma-glutamyl cycle. These studies illustrate the importance of astrocyte-mediated glutathione homeostasis for protection of neurons from rotenone and paraquat and the role of the gamma-glutamyl cycle in this neuroprotection. PMID- 22301168 TI - Dynamic and static mechanical analysis of resin luting cements. AB - Various types of indirect restorations are available for dental treatment and resin cements are commonly used as a luting medium. The aim of this study was to evaluate the mechanical properties of contemporary resin luting agents under different testing conditions and temperatures. The materials tested were Choice 2 (CH), Clearfil Esthetic Cement (EC), Resicem (RC) and RelyX Unicem (RX). Each material was examined after 24 h of storage at 21 degrees C dry and wet at 21, 37 and 50 degrees C under dynamic and static testing and parameters such as shear and flexural modulus, loss tangent, dynamic viscosity and Poisson's ratio were calculated. The resin cements were also subjected to creep testing under different constant loads for 3 h and a recovery time of 50 h. The material with the highest modulus was CH, while RX had the lowest. All resin cements were affected by the presence of water with RX being the least affected and by the increase of temperature, with RC being the least susceptible. None of the materials exhibited full recovery after creep testing and permanent deformation ranged from 0.43% to 5.53%. The resin cements tested in this study showed no major transitions under the different testing conditions. Their behavior was satisfactory for restorations that do not require increased mechanical properties. However, in the case of stress-bearing restorations the conditions in the oral cavity may affect the performance of these materials. PMID- 22301169 TI - Laser processed TiN reinforced Ti6Al4V composite coatings. AB - The purpose of this first generation investigation is to evaluate fabrication, in vitro cytotoxicity, cell-material interactions and tribological performance of TiN particle reinforced Ti6Al4V composite coatings for potential wear resistant load bearing implant applications. The microstructural analysis of the composites was performed using scanning electron microscope and phase analysis was done with X-ray diffraction. In vitro cell-material interactions, using human fetal osteoblast cell line, have been assessed on these composite coatings and compared with Ti6Al4V alloy control samples. The tribological performance of the coatings were evaluated, in simulated body fluids, up to 1000 m sliding distance under 10 N normal load. The results show that the composite coatings contain distinct TiN particles embedded in alpha+beta phase matrix. The average top surface hardness of Ti6Al4V alloy increased from 394+/-8 HV to 1138+/-61 HV with 40 wt% TiN reinforcement. Among the composite coatings, the coatings reinforced with 40 wt% TiN exhibited the highest wear resistance of 3.74*10(-6) mm(3)/Nm, which is lower than the wear rate, 1.04*10(-5) mm(3)/Nm, of laser processed CoCrMo alloy tested under identical experimental conditions. In vitro biocompatibility study showed that these composite coatings were non-toxic and provides superior cell-material interactions compared to Ti6Al4V control, as a result of their high surface energy. In summary, excellent in vitro wear resistance and biocompatibility of present laser processed TiN reinforced Ti6Al4V alloy composite coatings clearly show their potential as wear resistant contact surfaces for load bearing implant applications. PMID- 22301170 TI - Comparison of biaxial mechanical properties of coronary sinus tissues from porcine, ovine and aged human species. AB - Due to its proximity to the mitral valve, the coronary sinus (CS) vessel serves as a conduit for the deployment and implantation of the percutaneous transvenous mitral annuloplasty (PTMA) devices that can potentially reduce the mitral regurgitation. Because CS vessel is a venous tissue and seldom diseased, its mechanical properties have not been well studied. In this study, we performed a multi-axial mechanical test and histological analysis to characterize the mechanical and structural properties of the aged human, porcine and ovine CS tissues. The results showed that the aged human CS tissues exhibited much stiffer and highly anisotropic behaviors compared to the porcine and ovine. Both of the porcine and ovine CS vessel walls were thicker and mainly composed of striated muscle fibers (SMF), whereas the thinner aged human CS had higher collagen, less SMF, and more fragmented elastin fibers, which are possibly due to aging effects. We also observed that the anatomical features of porcine CS vessel might be not suitable for PTMA deployment. These differences between animal and human models raise questions for the validity of using animal models to investigate the biomechanics involved in the PTMA intervention. Therefore, caution must be taken in future studies of PTMA stents using animal models. PMID- 22301171 TI - Lubrication of metal-on-metal hip joints: the effect of protein content and load on film formation and wear. AB - Lubricant films were measured for a series of bovine serum and protein containing (albumin, globulin) saline solutions for CoCrMo femoral component sliding against a glass disc. Central film thickness was measured by optical interferometry as a function of time (constant mean speed: 0 and 10 mm/s) and variable mean speed (0 50 mm/s). The effect of load (5-20 N) on film thickness was also studied. The development of the wear scar on the CoCrMo surface was monitored by measuring the width of the contact zone during the film thickness tests. The results showed film thickness increased with time for both the static and sliding tests. Films formed in the static, loaded test were typically in the range of 3-40 nm. The globulin containing solutions formed the thickest films. In the sliding tests a wear scar rapidly formed on the implant component for the bovine serum and albumin fluids, negligible wear was observed for the globulin solutions. Film thickness increased with sliding time for all test solutions and was much greater than predicted by isoviscous EHL models. The film increase was found to correlate with increasing wear scar size and thus decreasing contact pressure. A new lubricating mechanism is proposed whereby during sliding the fluid undergoes bulk phase separation rheology, so that an elevated protein phase forms in the inlet zone. This protein phase is a high-viscosity biphasic matrix, which is periodically entrained into the contact forming a thick protective hydro-gel film. One of the main findings of this study is that film thickness was very sensitive to load; to a much greater extent than predicted by EHL models. Thus film formation in MoM hip joints is very susceptible to high contact pressures which might be due to implant misalignment and edge-loading. PMID- 22301172 TI - Experimental study of cancellous bone under large strains and a constitutive probabilistic model. AB - Experimental study of bovine cancellous bone up to compaction under uniaxial compression and up to fracture under tension, has been pursued in this article. Compression experiments have revealed the known three stages of the constitutive response, namely the initial increasing and softening branches at moderate strains, the plateau region at large strains and the hardening part at very large strains under compaction. Tension tests have quantified the increasing and softening branches of the stress-strain curve up to fracture. Subsequently, a constitutive mechanical model, for the simulation of the experimental findings up to very large strains (75% engineering strain under compression), is proposed. The model is based on the statistical description of (a) the failure process of the trabecular structure at small and moderate strains and (b) the compaction process of the trabecular mass at very large strains under compression. Several fitting cases indicated that the presented constitutive law can capture the evolution of the experimental results. PMID- 22301173 TI - Improved mechanical performance and delayed corrosion phenomena in biodegradable Mg-Zn-Ca alloys through Pd-alloying. AB - The influence of partial substitution of Mg by Pd on the microstructure, mechanical properties and corrosion behaviour of Mg(72-x)Zn(23)Ca(5)Pd(x) (x=0, 2 and 6 at.%) alloys, synthesized by copper mould casting, is investigated. While the Mg(72)Zn(23)Ca(5) alloy is mainly amorphous, the addition of Pd decreases the glass-forming ability, thus favouring the formation of crystalline phases. From a mechanical viewpoint, the hardness increases with the addition of Pd, from 2.71 GPa for x=0 to 3.9 GPa for x=6, mainly due to the formation of high-strength phases. In turn, the wear resistance is maximized for an intermediate Pd content (i.e., Mg(70)Zn(23)Ca(5)Pd(2)). Corrosion tests in a simulated body fluid (Hank's solution) indicate that Pd causes a shift in the corrosion potential towards more positive values, thus delaying the biodegradability of this alloy. Moreover, since the cytotoxic studies with mouse preosteoblasts do not show dead cells after culturing for 27 h, these alloys are potential candidates to be used as biomaterials. PMID- 22301174 TI - Mechanical properties, anisotropic swelling behaviours and structures of jellyfish mesogloea. AB - Learning from nature is a promising way for designing and fabricating new materials with special properties. As the first step, we need to understand the structures and properties of the natural materials. In this work, we paid attention to the mesogloea of an edible jellyfish (Rhopilema esculenta Kishinouye) and mainly focused on its structure, mechanical and swelling properties. Scanning electron microscope (SEM) investigations show that jellyfish mesogloea has a well-developed anisotropic microstructure, which consists of nano sized membranes connected with many fibres. The tensile and compressive properties of swollen and dried jellyfish mesogloea samples are measured. The jellyfish mesogloea displays very high tensile strength (0.17 MPa) and compressive strength (1.43 MPa) even with 99 wt % water. The mechanical properties of jellyfish mesogloea exceed most synthetic hydrogels with similar or even lower water contents. Swelling in acidic and basic buffer solutions weakens the mechanical properties of jellyfish mesogloea. The dried jellyfish mesogloea has very high tensile strength and modulus, which are very similar to those of synthetic plastics. The swelling properties of jellyfish mesogloea in solutions with different pH values were studied. The jellyfish mesogloea exhibits pH sensitive and anisotropic swelling properties. The jellyfish mesogloea swells (expands) in height but deswells (shrinks) in length and width, without significant change in the volume. This phenomenon has never been reported for synthetic hydrogels. This study may provide gel scientists new ideas in designing and fabricating hydrogels with well-defined microstructures and unique mechanical and swelling properties. PMID- 22301175 TI - Characterization of the effects of 3DSS peptide on remineralized enamel in artificial saliva. AB - Aspartate-serine-serine (DSS) repeats are abundant in naturally occurring proteins that are critical for tooth formation. In this study, we reported a possible role of triplet repeats of aspartate-serine-serine (3DSS) peptides in promoting mineral deposition onto human enamel from free ions. Human enamel specimens were acid demineralized, exposed briefly to 3DSS peptide solution, and then immersed in artificial saliva. At various stages of treatments, nanomechanical behaviors, surface morphology, surface roughness and the sorts of deposited minerals were characterized by nanoindentation, scanning electron microscopy (SEM), atomic force microscopy (AFM) and X-ray diffraction (XRD), respectively. The results indicated that treatment with 3DSS peptide promoted the uniform deposition of apatites with small crystalline size, in terms of prohibiting deformation, which resulted in a smaller average surface roughness and higher average values of nanohardness and elastic modulus of demineralized enamel treated with 33.3 MUM 3DSS peptide and immersed in artificial saliva compared to that without peptide treatment. PMID- 22301176 TI - Triblock copolymers of epsilon-caprolactone, trimethylene carbonate, and L lactide: effects of using random copolymer as hard-block. AB - A series of triblock copolymers comprising end block of PLLA modified with PCL, and random copolymer of PCL and PTMC as soft segment were synthesized. DSC data show that PCL disrupted the crystallinity of PLLA, making the hard block to be completely amorphous when the PCL content is 50%. Correspondingly, the addition of PCL into PLLA block enhances the elongation of the triblock considerably. With regards to the elasticity, however, creep test results show that adding PCL to PLLA block seems to reduce the "equilibrium" recovery, while cyclic test results shows that the instantaneous recovery increased significantly with more PCL inside PLLA block. It was also observed that the degradation rate of triblock with added PCL inside the PLLA was slower compared to triblock with pure PLLA hard block. Compared to biodegradable polyurethane, these polymers are expected to yield less harmful degradation products, and offer more variables for the manipulation of properties. These polymers are also processable from the melt at temperatures exceeding about 130 degrees C. We expect to use these polymers in a variety of applications, including stent coatings, fully-degradable stents and atrial septal defect occluders. PMID- 22301177 TI - Titanium and zirconium based alloys modified by intensive plastic deformation and nitrogen ion implantation for biocompatible implants. AB - Titanium and zirconium alloys are considered to be promising materials for orthopaedics because of their biocompatibility with tissues. Their main drawbacks for application as implants have generally been considered to be insufficient levels of mechanical and tribological properties. In this research the influence of equal channel angular pressing and nitrogen ion implantation on the structure and properties of Ti and Zr alloys has been investigated to ensure the optimum combination of the bulk material and surface layer properties. The data obtained showed that equal channel angular pressing and nitrogen ion implantation can be efficiently used to improve bulk and surface properties of Ti and Zr based implants. PMID- 22301178 TI - Comparative study on the mechanical and fracture properties of acrylic bone cements prepared with monomers containing amine groups. AB - In this work, the effect of the incorporation of comonomers containing amine groups on the mechanical and fracture properties of acrylic bone cements was studied. Cements were prepared with either diethyl amino ethyl acrylate (DEAEA), dimethyl amino ethyl methacrylate (DMAEM) or diethyl amino ethyl methacrylate (DEAEM) as comonomer in the liquid phase. It was found that strength and modulus decreased with increasing comonomer content in the bending and compressive tests. It was also observed that fracture toughness (K(IC)) and the critical strain energy release rate (G(IC)) increase with increasing comonomer concentration and are significantly higher compared to the control formulation. The mechanical and fracture properties of cements were also evaluated after soaking the specimens in Simulated Body Fluid (SBF) for 3 and 6 months. It was found that the mechanical properties of cements decreased when the samples were stored in SBF, although the impact strength increased in the first 3 months and then decreased. SEM micrographs were in agreement with the results obtained during mechanical characterization as the increase in toughness was confirmed by the appearance of ductile tearing pattern which is associated with plastic deformation. PMID- 22301179 TI - Compressive behavior of a turtle's shell: experiment, modeling, and simulation. AB - The turtle's shell acts as a protective armor for the animal. By analyzing a turtle shell via finite element analysis, one can obtain the strength and stiffness attributes to help design man-made armor. As such, finite element analysis was performed on a Terrapene carolina box turtle shell. Experimental data from compression tests were generated to provide insight into the scute through-thickness behavior of the turtle shell. Three regimes can be classified in terms of constitutive modeling: linear elastic, perfectly inelastic, and densification regions, where hardening occurs. For each regime, we developed a model that comprises elasticity and densification theory for porous materials and obtained all the material parameters by correlating the model with experimental data. The different constitutive responses arise as the deformation proceeded through three distinctive layers of the turtle shell carapace. Overall, the phenomenological stress-strain behavior is similar to that of metallic foams. PMID- 22301180 TI - Variation of the superelastic properties and nickel release from original and reused NiTi orthodontic archwires. AB - Reuse of NiTi orthodontic wires has become increasingly common in dental clinics. For sterilization and recovery of the original superelastic properties of the wires, a heat treatment is usually performed between 500 and 600 degrees C. The aim of this study was to analyze the effect of these thermal treatments on the mechanical behavior and the microstructure of NiTi archwires of different compositions. A reduction of the Ni content was observed in the matrix of the thermally treated archwires, due to the formation of Ti(3)Ni(4) precipitates. The nickel-rich precipitates were observed and characterized by Transmission Electron Microscopy (TEM) and electron diffraction. They were found to alter the mechanical properties of the wires, decreasing the transformation stresses, and causing a loss of activation of the NiTi archwires. The release of nickel was higher in the original archwires than in the reused ones, due to the matrix nickel depletion caused by the precipitation of Ti(3)Ni(4). PMID- 22301181 TI - Measuring residual stress in ceramic zirconia-porcelain dental crowns by nanoindentation. AB - Residual stress plays a critical role in failure of ceramic dental crowns. The magnitude and distribution of residual stress in the crown system are largely unknown. Determining the residual stress quantitatively is challenging since the crown has such complex contours and shapes. This work explored the feasibility and validity of measuring residual stress of zirconia and porcelain in ceramic crowns by nanoindentation. Nanoindentation tests were performed on the cross section of a crown for both porcelain and zirconia along four critical locations: the thickest, thinnest and medium porcelain thicknesses. Zirconia and porcelain pieces, chipped off from the crown and annealed at 400 degrees C, were used as reference samples. The residual stress was determined by comparing the measured hardness of the stressed sample with that of the reference sample. Nanoindentation impression images were acquired through a scanning probe microscope (SPM) equipped with a Hysitron Triboindenter. Zirconia showed large pile-up. Residual stress is determined along the thickness of crowns at the chosen locations for both porcelain and zirconia. The measured results were compared with the results from X-ray diffraction (XRD) and finite element modeling (FEM). Results show there are large amounts of residual stresses in the dental crown and their magnitude differs between locations due to the complex shape of the crown. The average residual stress readings were as high as -637 MPa and 323 MPa for zirconia and porcelain respectively. PMID- 22301182 TI - Using scratch testing to measure the adhesion strength of calcium phosphate coatings applied to poly(carbonate urethane) substrates. AB - Bioactive coatings are applied to components of modern orthopaedic implants to improve the host tissue response to the implants. Such coatings cannot be applied to polymeric implants by high-temperature techniques, because the use of high temperatures may critically degrade the polymer substrate. Regardless of the coating technique that is used, the coating must be sufficiently well adhered to the underlying substrate to provide any practical benefit. This paper investigates the use of scratch testing to measure the adhesion strength of calcium phosphate (CaP) coatings that were applied to a poly(carbonate urethane) (PCU) substrate by an aqueous process at temperatures of 19, 28, 37, and 50 degrees C. This work represents the first time that scratch testing analysis has been used to study CaP coatings deposited by an aqueous, low-temperature process on to a polymer substrate. Scratch testing was shown to be a useful technique for obtaining comparative, rather than absolute, values of adhesion strength for hard coatings formed on a compliant substrate. Generally, the coating temperature was not found to influence the CaP-PCU adhesion strength. Although CaP coatings formed at 19 degrees C exhibited considerably lower adhesion strengths than CaP coatings formed at 28, 37, and 50 degrees C, this finding was attributable to the inconsistency of CaP coatings formed on the PCU substrates at 19 degrees C. The coating-substrate adhesion strength was measured for CaP coatings of four different coating ages (0, 1, 2, and 3 years). CaP coatings that were aged for 0, 1, or 2 years exhibited similar coating-substrate adhesion strengths to each other. In contrast, CaP coatings that were aged for 3 years demonstrated considerably lower coating-substrate adhesion strengths. The observed reduction in adhesion strength with age was thought to be attributable to suspected "drying out" of the CaP coatings. PMID- 22301183 TI - The fracture toughness of soft tissues. AB - Fracture toughness is important for any material, but to date there have been few investigations of this mechanical property in soft mammalian tissues. This paper presents new data on porcine muscle tissue and a detailed analysis of all previous work. The conclusion is that, in most cases, fracture toughness has not in fact been measured for these tissues. Reanalysis of the previous work shows that failure of the test specimens generally occurred at the material's ultimate strength, implying that no information about toughness can be obtained from the results. This finding applied to work on cartilage, artificial neocartilage, muscle and the TMJ disc. Our own data, which was also found to be invalid, gave measured fracture toughness values which were highly variable and showed a strong dependence on the crack growth increment. The net-section failure stress and failure energy were relatively constant in large specimens, independent of crack length, whilst for smaller specimens they showed a strong size effect. These findings are explained by the fact that the process zone size, estimated here using the critical distance parameter L, was similar to, or larger than, critical specimen dimensions (crack length and specimen width). Whilst this analysis casts doubt on much of the published literature, a useful finding is that soft tissues are highly tolerant of defects, able to withstand the presence of cracks several millimetres in length without significant loss of strength. PMID- 22301184 TI - Micromechanical analysis of native and cross-linked collagen type I fibrils supports the existence of microfibrils. AB - The mechanical properties of individual collagen fibrils of approximately 200 nm in diameter were determined using a slightly adapted AFM system. Single collagen fibrils immersed in PBS buffer were attached between an AFM cantilever and a glass surface to perform tensile tests at different strain rates and stress relaxation measurements. The stress-strain behavior of collagen fibrils immersed in PBS buffer comprises a toe region up to a stress of 5 MPa, followed by the heel and linear region at higher stresses. Hysteresis and strain-rate dependent stress-strain behavior of collagen fibrils were observed, which suggest that single collagen fibrils have viscoelastic properties. The stress relaxation process of individual collagen fibrils could be best fitted using a two-term Prony series. Furthermore, the influence of different cross-linking agents on the mechanical properties of single collagen fibrils was investigated. Based on these results, we propose that sliding of microfibrils with respect to each other plays a role in the viscoelastic behavior of collagen fibrils in addition to the sliding of collagen molecules with respect to each other. Our finding provides a better insight into the relationship between the structure and mechanical properties of collagen and the micro-mechanical behavior of tissues. PMID- 22301185 TI - Tissue deformation analysis using a laser based digital image correlation technique. AB - A laser based technique for planar time-resolved measurements of tissue deformation in transparent biomedical materials with high spatial resolution is developed. The approach is based on monitoring the displacement of micrometer particles previously embedded into a semi-transparent sample as it is deformed by some form of external loading. The particles are illuminated in a plane inside the tissue material by a thin laser light sheet, and the pattern is continuously recorded by a digital camera. Image analysis yields the locally and temporally resolved sample deformation in the measurement plane without the need for any in situ measurement hardware. The applicability of the method for determination of tissue deformation and material strain during the insertion of a needle probe into a soft material sample is demonstrated by means of an in vitro trial on gelatin. PMID- 22301186 TI - Towards child versus adult brain mechanical properties. AB - The characterization of brain tissue mechanical properties is of crucial importance in the development of realistic numerical models of the human head. While the mechanical behavior of the adult brain has been extensively investigated in several studies, there is a considerable paucity of data concerning the influence of age on mechanical properties of the brain. Therefore, the implementation of child and infant head models often involves restrictive assumptions like properties scaling from adult or animal data. The present study presents a step towards the investigation of the effects of age on viscoelastic properties of human brain tissue from a first set of dynamic oscillatory shear experiments. Tests were also performed on three different locations of brain (corona radiata, thalamus and brainstem) in order to investigate regional differences. Despite the limited number of child brain samples a significant increase in both storage and loss moduli occurring between the age of 5 months and the age of 22 months was found, confirmed by statistical Student's t-tests (p=0.104,0.038 and 0.054 for respectively corona radiata, thalamus and brain stem samples locations respectively). The adult brain appears to be 3-4 times stiffer than the young child one. Moreover, the brainstem was found to be approximately 2 3 times stiffer than both gray and white matter from corona radiata and thalamus. As a tentative conclusion, this study provides the first rheological data on the human brain at different ages and brain regions. This data could be implemented in numerical models of the human head, especially in models concerning pediatric population. PMID- 22301187 TI - Characterization of the mechanical properties of a new grade of ultra high molecular weight polyethylene and modeling with the viscoplasticity based on overstress. AB - Enhancements to the service life and performance of orthopedic implants used in total knee and hip replacement procedures can be achieved through optimization of design and the development of superior biocompatible polymeric materials. The introduction of a new or modified polymer must, naturally, be preceded by a rigorous testing program. This paper presents the assessment of the mechanical properties of a new filled grade of ultra high molecular weight polyethylene (UHMWPE) designated AOX(TM) and developed by DePuy Orthopaedics Inc. The deformation behavior was investigated through a series of tensile and compressive tests including strain rate sensitivity, creep, relaxation, and recovery. The polymer was found to exhibit rate-reversal behavior for certain loading histories: strain rate during creep with a compressive stress can be negative, positive, or change between the two during a test. Analogous behavior occurs during relaxation as well. This behavior lies beyond the realm of most numerical models used to computationally investigate and improve part geometry through finite element analysis of components. To address this shortcoming, the viscoplasticity theory based on overstress (VBO) has been suitably modified to capture these trends. VBO is a state variable based model in a differential formulation. Numerical simulation and prediction of all of the aforementioned tests, including good reproduction of the rate reversal behavior, is presented in this study. PMID- 22301188 TI - Modification of alginate degradation properties using orthosilicic acid. AB - Biopolymers such as alginates have been widely researched for clinical use. Their clinical application, however, have been limited due to their unpredictable and often rapid degradation rates. Here we show that the degradation of an alginate hydrogel can be tailored through the addition of orthosilicic acid (OSA). On immersion in aqueous media a negligible quantity of orthosilicic acid was released from the gel matrix. The presence of the OSA within the gel was shown to significantly slow degradation of the alginate hydrogel when immersed in a potent calcium chelator (EDTA) when compared with the control group. Sample degradation was associated with a significant calcium release from the non-modified gel; however, the orthosilicic acid modified gel did not release detectable levels of calcium over the same period. This suggests that the orthosilicic acid inhibits degradation of the gel by forming an interaction with the calcium cross-links. A rapid reduction in the storage modulus G', was observed in alginate made without OSA, however, the G'exhibited by the orthosilicic acid modified alginate did not reduce significantly (p<0.05). Furthermore, although both the OSA and alginate exhibit negative charges in solution, it is likely that they form weak interactions, this hypothesis was proven by demonstrating the efficacy of OSA for binding the alginate hydrocolloid. The findings of this study are likely to have utility in applications where controlling gel degradation is desirable, such as in cell delivery or in the controlled release of molecules in the body. PMID- 22301189 TI - Number of mitochondria in tissue. PMID- 22301190 TI - A p53-inducible microRNA-34a downregulates Ras signaling by targeting IMPDH. AB - p53 is a well-known transcription factor that controls cell cycle arrest and cell death in response to a wide range of stresses. Moreover, p53 regulates glucose metabolism and its mutation results in the metabolic switch to the Warburg effect found in cancer cells. Nucleotide biosynthesis is also critical for cell proliferation and the cell division cycle. Nonetheless, little is known about whether p53 regulates nucleotide biosynthesis. Here we demonstrated that p53 inducible microRNA-34a (miR-34a) repressed inosine 5'-monophosphate dehydrogenase (IMPDH), a rate-limiting enzyme of de novo GTP biosynthesis. Treatment with anti miR-34a inhibitor relieved the expression of IMPDH upon DNA damage. Ultimately, miR-34a-mediated inhibition of IMPDH resulted in repressed activation of the GTP dependent Ras signaling pathway. In summary, we suggest that p53 has a novel function in regulating purine biosynthesis, aided by miR-34a-dependent IMPDH repression. PMID- 22301191 TI - Anti-mitotic potential of 7-diethylamino-3(2'-benzoxazolyl)-coumarin in 5 fluorouracil-resistant human gastric cancer cell line SNU620/5-FU. AB - In this study, we investigate an anti-mitotic potential of the novel synthetic coumarin-based compound, 7-diethylamino-3(2'-benzoxazolyl)-coumarin, in 5 fluorouracil-resistant human gastric cancer cell line SNU-620-5FU and its parental cell SNU-620. It exerts the anti-proliferative effects with similar potencies against both cancer cells, which is mediated by destabilization of microtubules and subsequent mitotic arrest. Furthermore, this compound enhances caspase-dependent apoptotic cell death via decreased expression of anti-apoptotic genes. Taken together, our data strongly support anti-mitotic potential of 7 diethylamino-3(2'-benzoxazolyl)-coumarin against drug-resistant cancer cells which will prompt us to further develop as a novel microtubule inhibitor for drug resistant cancer chemotherapy. PMID- 22301192 TI - Novel agents for the treatment of HIV-2 infection. AB - Many of the antiretrovirals used against HIV-1 are either ineffective or less effective in HIV-2 infection. There is in vitro evidence of the potency of maraviroc and several investigational agents against HIV-2. We conclude that, whilst specific boosted protease inhibitors combined with nucleoside analogues should still be considered the mainstays of HIV-2 treatment, maraviroc, T-1249, TAK-779 and AMD3100, as well as raltegravir, could contribute to regimens for treatment-experienced individuals. Factors bearing on the use and timing of these alternative agents are discussed. PMID- 22301193 TI - Strategies of newcastle disease vaccination for commercial ostrich farms in Japan. AB - Strategies of Newcastle disease (ND) vaccination were demonstrated in a commercial ostrich farm in Japan. Three of 13 seven-month-old ostriches kept in a pen were vaccinated with a live ND vaccine by eye dropping for the 1st and 2nd vaccinations and spraying for the 3rd to 5th vaccinations. Antibodies against ND virus (NDV) were detected in all of the unvaccinated ostriches by virus neutralization test. At 2.5 months post final vaccination, 2 ostriches introduced into the pen raised antibodies against NDV. These data indicate that NDV may be transmitted from vaccinated to unvaccinated ostriches in the flock and that the virus may be sustained for a certain period in the flock. These data may be helpful for ND vaccination management in ostrich farms. PMID- 22301194 TI - Effects of Food and Drug Administration-approved medications for Alzheimer's disease on clinical progression. AB - BACKGROUND: Observational studies suggest that cholinesterase inhibitors and/or memantine may delay clinical progression of Alzheimer's disease (AD) in 40% of individuals taking the medications. Given this response and existence of side effects, we sought to quantify medication use and benefits in a population-based study of incident AD cases. METHODS: The Cache County Dementia Progression Study enrolled and followed a cohort of 327 incident AD cases for a maximum of 9 years. Drug exposure was expressed using a persistency index (PI), calculated as total years of drug use divided by total years of observation. Linear mixed-effects models examined PI, and interactions with sex and apolipoprotein E (APOE) as predictors of clinical progression on the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes. RESULTS: A total of 69 participants (21.1%) reported having ever used cholinesterase inhibitors or memantine. There was a strong three-way interaction between PI, sex, and time. Among women, a higher PI (i.e., greater duration of use) of cholinesterase inhibitors was associated with slower progression on the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes, particularly among those with an APOE E4 allele. In contrast, higher PI was associated with faster progression in males. CONCLUSION: A low percentage of individuals with AD in the community are taking cholinesterase inhibitors or memantine. This study suggests that women, particularly those with an APOE E4 allele, may benefit the most from these medications. With the newly approved increased dose of donepezil, it will be imperative to determine whether a higher dose is needed in men or whether other factors warrant consideration. PMID- 22301196 TI - Transforming semi-structured life science diagrams into meaningful domain ontologies with DiDOn. AB - Bio-ontology development is a resource-consuming task despite the many open source ontologies available for reuse. Various strategies and tools for bottom-up ontology development have been proposed from a computing angle, yet the most obvious one from a domain expert perspective is unexplored: the abundant diagrams in the sciences. To speed up and simplify bio-ontology development, we propose a detailed, micro-level, procedure, DiDOn, to formalise such semi-structured biological diagrams availing also of a foundational ontology for more precise and interoperable subject domain semantics. The approach is illustrated using Pathway Studio as case study. PMID- 22301195 TI - Citalopram for agitation in Alzheimer's disease: design and methods. AB - BACKGROUND: Agitation is one of the most common neuropsychiatric symptoms of Alzheimer's disease (AD), and is associated with serious adverse consequences for patients and caregivers. Evidence-supported treatment options for agitation are limited. The citalopram for agitation in Alzheimer's disease (CitAD) study was designed to evaluate the potential of citalopram to ameliorate these symptoms. METHODS: CitAD is a randomized, double-masked, placebo-controlled multicenter clinical trial, with two parallel treatment groups assigned in a 1:1 ratio and randomization stratified by clinical center. The study included eight recruiting clinical centers, a chair's office, and a coordinating center located in university settings in the United States and Canada. A total of 200 individuals having probable AD with clinically significant agitation and without major depression were recruited for this study. Patients were randomized to receive citalopram (target dose of 30 mg/d) or matching placebo. Caregivers of patients in both treatment groups received a structured psychosocial therapy. Agitation was compared between treatment groups using the NeuroBehavioral Rating Scale and the AD Cooperative Study- Clinical Global Impression of Change, which are the primary outcomes. Functional performance, cognition, caregiver distress, and rates of adverse and serious adverse events were also measured. CONCLUSION: The authors believe the design elements in CitAD are important features to be included in trials assessing the safety and efficacy of psychotropic medications for clinically significant agitation in AD. PMID- 22301197 TI - Development of a new quantitative real-time HHV-6-PCR and monitoring of HHV-6 DNAaemia after liver transplantation. AB - A quantitative HHV-6 PCR (qPCR) assay was developed and compared to an "in-house" qualitative PCR and to the commercial quantitative Argene CMV, HHV6, 7, 8 R geneTM test. Clinical specimens consisting of 127 whole blood and 57 cerebrospinal fluid (CSF) specimens were tested using the two qPCRs and the qualitative PCR in parallel. When the qualitative PCR was used as a "gold standard," the sensitivities of the qPCRs for the blood samples were 86% for the "in-house" qPCR and 76% for the Argene's test and the specificities were 96% and 92%, respectively. With CSF specimens the sensitivities were 92% and 80% and the specificities 98% and 82%, respectively. Furthermore, the two qPCRs were compared in the monitoring of liver transplant patients and retrospectively correlated to HHV-6 antigenaemia. In total, 223 blood specimens were tested. HHV-6 antigenaemia had been found in 21/36 (58%) patients and HHV-6 DNAaemia was demonstrated in 18/36 (50%). Viral loads by the "in-house" test varied from 280 to 19700 copies/ml (median 1200) and by Argene's test from 120 to 24070 copies/ml (median 458). The correlation of viral loads between the two qPCRs was good (R=0.94, p<0.01). The new in-house test was found to be reliable for the detection and quantitation of HHV-6 DNA in clinical specimens. PMID- 22301198 TI - The relationship between the regional abdominal adipose tissue distribution and the serum uric acid levels in people with type 2 diabetes mellitus. AB - BACKGROUND: Hyperuricemia is associated with obesity. The visceral adiposity and subcutaneous adiposity may be associated with the differential metabolic risk, and the distribution of abdominal adipose tissue was significantly altered in people with type 2 diabetes mellitus (DM) compared to healthy people. Our study was performed to determine to the association between the regional abdominal adipose tissue distribution and serum uric acid levels in people with type 2 DM. METHODS: A total of 699 people with type 2 DM and who had undergone abdominal computed tomography assessment of the visceral fat area and subcutaneous fat area were included. The serum uric acid levels were measured by the uricase method. Hyperuricemia was defined by cut-off value of > 7 mg/dl for men and > 6 mg/dl for women. RESULTS: The visceral fat area was positively associated with the serum uric acid levels after adjustment for age, sex, systolic blood pressure, diastolic blood pressure, serum creatinine, hemoglobin, serum albumin, serum high density lipoprotein, serum triglyceride and hemoglobin A1c (beta-coefficient = 0.117, p < 0.001). The logistic regression analysis showed that the visceral fat area was the significant independent predictor of hyperuricemia (OR 2.33, 95% CI, 1.21-4.50, p = 0.012). But there was no significant association between the subcutaneous fat area and the serum uric acid levels (beta-coefficient = 0.061, p = 0.255). CONCLUSIONS: our data shows that the visceral fat area was positively associated with the serum uric acid levels, but the subcutaneous fat area was not in people with type 2 DM. PMID- 22301199 TI - [An uncommon complication of unsafe induced abortion: bowel prolapse through uterine perforation]. AB - The authors report one case of bowel prolapse through uterus following induced abortion. The eviscerated bowel was completely gangrenous, devoided from its mesentery and entrapped in the uterus wall. The treatment was a bowel resection and ileo-ileum anastomosis; the uterus was evacuated of retained products of conception and then sutured. The patient recovered uneventfully; fertility prognosis is expected to be poor because of abortion sequelae. If the abortion law still remains in Ivory Coast, more effort should be directed at reducing the incidence of unwanted pregnancy. This could be best archived by a better information on contraception and better health education programs. PMID- 22301200 TI - Patch testing and allergen-specific serum IgE and IgG antibodies in the diagnosis of canine adverse food reactions. AB - Adverse food reaction (AFR) is a common differential diagnosis for pruritic dogs. The only way to diagnose AFR is an elimination diet of 6-8 weeks with a protein and a carbohydrate source not previously fed. In humans, patch testing has been shown to be a useful tool to diagnose food allergies. In veterinary medicine, serum food allergen-specific antibody testing is widely offered to identify suitable ingredients for such diets. The aim of this study was to determine sensitivity, specificity, negative and positive predictability of patch testing with and serum antibody testing for a variety of common food stuffs. Twenty-five allergic dogs underwent an elimination diet and individual rechallenge with selected food stuffs, food patch testing and serum testing for food-antigen specific IgE and IgG. Eleven clinically normal control dogs only were subjected to patch and serum testing. The sensitivity and specificity of the patch test were 96.7 and 89.0% respectively, negative and positive predictability were 99.3 and 63.0%. For IgE and IgG the sensitivity was 6.7 and 26.7%, specificity were 91.4 and 88.3%, the negative predictive values 80.7 and 83.7% and the positive predictive values were 15.4 and 34.8%. Based on these results, a positive reaction of a dog on these tests is not very helpful, but a negative result indicates that this antigen is tolerated well. We conclude that patch testing (and to a lesser degree serum testing) can be helpful in choosing ingredients for an elimination diet in a dog with suspected AFR. PMID- 22301201 TI - Identical sequence patterns in the ends of exons and introns of human protein coding genes. AB - Intron splicing is one of the most important steps involved in the maturation process of a pre-mRNA. Although the sequence profiles around the splice sites have been studied extensively, the levels of sequence identity between the exonic sequences preceding the donor sites and the intronic sequences preceding the acceptor sites has not been examined as thoroughly. In this study we investigated identity patterns between the last 15 nucleotides of the exonic sequence preceding the 5' splice site and the intronic sequence preceding the 3' splice site in a set of human protein-coding genes that do not exhibit intron retention. We found that almost 60% of consecutive exons and introns in human protein-coding genes share at least two identical nucleotides at their 3' ends and, on average, the sequence identity length is 2.47 nucleotides. Based on our findings we conclude that the 3' ends of exons and introns tend to have longer identical sequences within a gene than when being taken from different genes. Our results hold even if the pairs are non-consecutive in the transcription order. PMID- 22301202 TI - The teaching of anesthesia history in US residency programs: results of a nationwide survey. AB - STUDY OBJECTIVE: To determine the extent to which history of anesthesia-related topics are included in the didactic curriculum of United States residency programs in anesthesiology. DESIGN: Survey instrument. SETTING: University affiliated hospital. MEASUREMENTS: In addition to information related to the identity of the respondent and institution, we inquired about the presence of faculty members with an interest in the history of anesthesia (HOA), the inclusion of HOA-related lectures in the didactic curriculum, whether the program would consider inviting an outside lecturer for a session devoted to HOA, the inclusion of HOA-related tours, and whether the program would allow residents an elective rotation of one to three months devoted to a research project related to HOA. MAIN RESULTS: On the basis of responses from 46 of 132 residency programs (35%), 54% of programs had at least one faculty member with an interest in HOA, and 45% of programs included lectures related to HOA in their didactic curriculum. An encouraging finding was that 83% of programs (without such didactic sessions) were willing to invite visiting professors to deliver lectures on HOA. The vast majority (91%) did not conduct tours related to HOA, while 74% indicated a willingness to allow residents interested in HOA to devote one to three months to undertake such projects. CONCLUSIONS: The low rate of interest in HOA among faculty members, and the lower rate of inclusion of lectures related to HOA during residency training, suggests that substantial barriers exist within the academic community towards a wider acceptance of the importance of HOA. Two positive indicators were the willingness to invite outside speakers and the receptivity to allowing residents to devote one to three months to projects related to HOA. PMID- 22301203 TI - Low social support is associated with an increased risk of postoperative delirium. AB - STUDY OBJECTIVE: To examine the predictive value of social support in postoperative delirium. DESIGN: Prospective observational study. SETTING: Postoperative recovery room and orthopedic surgery department. PATIENTS: 106 consecutive patients undergoing a planned orthopedic surgery with general anesthesia. MEASUREMENTS: All patients completed questionnaires to assess depressive mood (the Beck Depression Inventory) and social support (Sarason's Social Support Questionnaire) during the preanesthesia visit. Postoperative delirium symptoms were assessed daily using the Memorial Delirium Assessment Scale. Demographic, clinical, and biological data, including anesthesia procedure, were recorded. MAIN RESULTS: Controlling for various potential confounders through multivariate binary logistic regression, postoperative delirium was independently predicted by satisfaction with social support, but neither by depressive mood nor the number of supportive persons. Other significant predictors were the preoperative use of benzodiazepines, age, and type of surgery. CONCLUSION: Patients who report low satisfaction with social support may present with a particular vulnerability to postoperative delirium, even after controlling for physical confounding variables and depressive mood. PMID- 22301204 TI - Shoulder and head elevation improves laryngoscopic view for tracheal intubation in nonobese as well as obese individuals. AB - STUDY OBJECTIVE: To determine whether shoulder and head elevation, such that the patient's ear lies at or higher than the sternum ("ramp"), improves laryngoscopic grade in adult patients of various body mass index (BMI) values. DESIGN: Prospective, unblinded study, with patients and laryngoscopists acting as their own controls. SETTING: Operating room of a university-affiliated hospital. PATIENTS: 189 adult ASA physical status 1, 2, and 3 patients. INTERVENTIONS: After performing a standard preoperative airway evaluation and inducing general anesthesia, the anesthetist performed and graded two laryngoscopies: one in the "ramp" position and one in the "sniff" position. MEASUREMENTS: Patient BMI, Mallampati airway class, thyromental distance, neck circumference, cervical extension ability, Cormack and Lehane laryngoscopic grade for each laryngoscopy, subjective lifting force required, and need for external laryngeal pressure were recorded. MAIN RESULTS: Use of the "ramp" provided significantly better or equal laryngoscopic views, relative to those with the "sniff" position, in the entire study population. CONCLUSIONS: Shoulder and head elevation by any means that brings the patient's sternum onto the horizontal plane of the external auditory meatus maintains or improves laryngoscopic view significantly. PMID- 22301205 TI - Hemodynamic effects of laparoscopic radiofrequency ablation of liver tumors versus laparoscopic hepatic ultrasound examination. AB - STUDY OBJECTIVE: To compare the hemodynamic changes that occur during laparoscopic radiofrequency ablation of liver metastases with those occurring during laparoscopic ultrasound hepatic examination alone. DESIGN: Prospective, observational study. SETTING: Operating rooms of a university-affiliated hospital. PATIENTS: 40 ASA physical status 2 and 3 patients with liver metastases. INTERVENTIONS: 20 patients underwent laparoscopic radiofrequency ablation of liver tumors following laparoscopic ultrasound examination, and 20 had laparoscopic ultrasound examination alone. The anesthetic technique was standardized. MEASUREMENTS: The primary endpoint of the study was the number of episodes of mean arterial pressure (MAP) < 70 mmHg. Secondary endpoints were significant differences between the groups in MAP, heart rate, cardiac index, ejection fraction (EF; both measured with thoracic bioimpedance), calculated systemic vascular resistance index (SVRI), and central venous pressure. MAIN RESULTS: The number of episodes of MAP < 70 mmHg did not differ between groups: there were 9 episodes in the ultrasound alone group and 7 in the radiofrequency group (P = 0.668). Cardiac index, EF, and SVRI were similar between groups. Central venous pressure was slightly higher in the radiofrequency group [11.99 (10.8-13.2) mmHg vs. 10.3 (9.2-11.4) mmHg, P = 0.04]. CONCLUSIONS: Hemodynamic profiles were similar when comparing laparoscopic radiofrequency ablation of liver metastases with laparoscopic ultrasound hepatic examination alone. PMID- 22301206 TI - Optimal shoulder roll height for internal jugular venous cannulation: a study of awake adult volunteers. AB - STUDY OBJECTIVE: To explore the influence of shoulder roll height on internal jugular vein (IJV) diameter and IJV/common carotid artery (CCA) overlap. DESIGN: Cross-sectional study. SETTING: University-affiliated hospital. PATIENTS: 40 healthy participants. MEASUREMENTS: Ultrasonography to measure the effects of using shoulder rolls ranging between 0 and 5 cm high on IJV diameter, CCA diameter, and percentage overlap of the CCA. MAIN RESULTS: The percentage overlap of CCA decreased for both left (LIJV) and right IJV (RIJV) with the use of higher shoulder rolls. Greater values were seen in depth from skin surface to anterior wall of left IJV in almost all stages, with the exception of Stages 0 and 1 (P < 0.016); and the use of a 5 cm shoulder roll resulted in a significantly decreased anteroposterior (AP) diameter of both RIJVs and LIJVs (both P < 0.008). CONCLUSIONS: Shoulder rolls can reduce the overlap between the IJV and CCA, and may be useful in positioning patients for IJV puncture. PMID- 22301207 TI - Systemic lidocaine decreases the Bispectral Index in the presence of midazolam, but not its absence. AB - STUDY OBJECTIVE: To evaluate the effects of intravenous (IV) lidocaine on the Bispectral Index (BIS) in the presence or absence of midazolam. DESIGN: Prospective, randomized, double-blinded, placebo-controlled clinical study. SETTING: Operating room of a university hospital. PATIENTS: 96 ASA physical status 1, 2, and 3 patients undergoing general anesthesia. INTERVENTIONS: Patients were assigned to one of 6 treatment groups to receive IV midazolam (0.03 mg/kg) or placebo, followed 5 minutes later by one of three IV preinduction doses of lidocaine: 0.5, 1.0, or 1.5 mg/kg. MEASUREMENTS: BIS values were recorded before administration of lidocaine and at 30-second intervals afterwards for three minutes. The primary endpoint was the average BIS level recorded. MAIN RESULTS: Baseline BIS values were lower in the midazolam group (94 +/- 4 vs. 90 +/- 7, P < 0.001). There was no significant decrease in BIS values in the placebo group for any of the three lidocaine doses. However, in the midazolam groups, significant decreases in BIS levels versus baseline values were measured. CONCLUSION: IV lidocaine decreases BIS in the presence of midazolam, suggesting that the effect of lidocaine on BIS is not direct, but rather results from modulation by midazolam. PMID- 22301208 TI - Does the covering of children during induction of anesthesia have an effect on body temperature at the end of surgery? AB - STUDY OBJECTIVES: To determine whether the covering of healthy children during anesthetic induction reduces hypothermia at the end of minor surgeries. DESIGN: Randomized, single-blinded, prospective study. SETTING: Operating room and postoperative recovery area of a university-affiliated hospital. PATIENTS: 50 ASA physical status 1 patients, aged 6 months to 3.5 years, scheduled for simple urological surgeries. INTERVENTIONS: Subjects were randomly assigned to one of two groups: covered or uncovered. Children in the covered group (Group C) were actively warmed on arrival in the operating room (OR) using cotton blankets and a warm forced-air blanket set at 43 degrees C. Children in the uncovered group (Group U) remained uncovered during the induction of general anesthesia. Children in both groups were actively warmed following placement of surgical drapes. MEASUREMENTS: Temperature (in Celsius) during the study procedure was recorded for each patient. MAIN RESULTS: Mean core body temperature at the end of induction did not differ in the two groups, 36.4 degrees C in Group C and 36.6 degrees C in Group U. Mean core body temperature at the end of surgery did not differ between the two groups: 36.9 degrees C in Group C and 37.0 degrees C in Group U. CONCLUSION: Leaving healthy children uncovered during induction of general anesthesia does not have a clinically significant effect on core temperature at the end of induction or of surgery. PMID- 22301209 TI - Unanticipated dispositions after ambulatory surgery: an important topic with multiple factors. PMID- 22301210 TI - Results for primary bypass versus primary angioplasty/stent for intermittent claudication due to superficial femoral artery occlusive disease. AB - BACKGROUND: Percutaneous transluminal angioplasty +/- stent (PTA/S) and surgical bypass are both accepted treatments for claudication due to superficial femoral artery (SFA) occlusive disease. However, long-term results comparing these modalities for primary intervention in patients who have had no prior intervention have not been reported. We report our results with 3-year follow-up. METHODS: We reviewed all lower extremity bypass procedures at Beth Israel Deaconess Medical Center from 2001 through 2009 and all PTA/S performed from 2005 through 2009 for claudication. We excluded all limb salvage procedures and included only those that were undergoing their first intervention for claudication due to SFA disease. We recorded patient demographics, comorbidities, perioperative medications, TASC classification, and runoff. Outcomes included complications, restenosis, symptom recurrence, reinterventions, major amputation, and mortality. RESULTS: We identified 113 bypass grafts and 105 PTA/S of femoral popliteal lesions without prior interventions. Bypasses were above the knee in 62% (45% vein) and below the knee in 38% (100% vein). Mean age was 63 (bypass) versus 69 (PTA/S; P < .01). Mean length of stay (LOS) was 3.9 versus 1.2 days (P < .01). Bypass grafts were used less for TASC A (17% vs 40%; P < .01) and more for TASC C (36% vs 11%; P < .01) and TASC D (13% vs 3%; P < .01) lesions. There were no differences in perioperative (2% vs 0%; not significant [NS]) or 3-year mortality (9% vs 8%; NS). Wound infection was higher with bypass (16% vs 0%; P < .01). None involved grafts. Bypass showed improved freedom from restenosis (73% vs 42% at 3 years; hazard ratio [HR], 0.4; 95% confidence interval [CI], .23 .71), symptom recurrence (70% and 36% at 3 years; HR, 0.37; 95% CI, .2-.56), and freedom from symptoms at last follow-up (83% vs 49%; HR, 0.18; 95% CI, .08-.40). There was no difference in freedom from reintervention (77% vs 66% at 3 years; NS). Multivariable analysis of all patients showed that restenosis was predicted by PTA/S (HR, 2.5; 95% CI, 1.4-4.4) and TASC D (HR, 3.7; 95% CI, 3.5-9) lesions. Recurrence of symptoms was similarly predicted by PTA/S (HR, 3.0; 95% CI, 1.8-5) and TASC D lesions (HR, 3.1; 95% CI, 1.4-7). Statin use postoperatively was predictive of patency (HR, 0.6; 95% CI, .35-.97) and freedom from recurrent symptoms (HR, 0.6; 95% CI, .36-.93). CONCLUSIONS: Surgical bypass for the primary treatment of claudication showed improved freedom from restenosis and symptom relief despite treatment of more extensive disease, but was associated with increased LOS and wound infection. Statins improved freedom from restenosis and symptom recurrence overall. PMID- 22301211 TI - First results of clampless distal anastomosis in peripheral vascular bypass with LeGoo, a thermoreversible polymer. AB - BACKGROUND: We report our initial experience with LeGoo (Pluromed Inc, Woburn, Mass), a temporary thermoreversible occlusive gel, in peripheral vascular revascularization. METHODS: Between 2007 and 2010, LeGoo was used to occlude target vessels during bypass surgery in 14 patients who required infrainguinal revascularization. RESULTS: Proximal occlusion of the target vessel was obtained with a mean quantity of 0.25 mL of LeGoo. Distal occlusion of the vessel was obtained with a mean quantity of 0.28 mL. One injection of LeGoo was sufficient to prevent backbleeding in 11 of 14 patients. The mean occlusion time was 13.4 +/ 3.3 minutes. An injection of saline through the graft or better directly into the arteries was used to dissolve the gel. For our first case, a Fogarty catheter was used to remove residual gel from the anterior tibial artery. CONCLUSIONS: LeGoo gel can be used to stop blood flow in small-bore arteries in the lower limbs to allow anastomoses to be performed. PMID- 22301212 TI - Duplex velocity criteria for native celiac/superior mesenteric artery stenosis vs in-stent stenosis. AB - BACKGROUND: Duplex velocity criteria (DVC) to identify in-stent celiac artery (CA) and superior mesenteric artery (SMA) stenosis is not well defined. Only one study has been published which concluded that DVC for native SMA stenosis overestimated stenosis in stented SMAs. The purpose of this study was to analyze DVC in detecting CA/SMA in-stent stenosis (ISS). METHODS: Forty-three patients with 62 stents (32 SMAs and 30 CAs), who had concurrent postoperative duplex ultrasound scan and angiograms for significant ISS by DVC were analyzed. A receiver operator curve (ROC) analysis was used to determine optimal DVC (peak systolic velocity [PSV], end-diastolic velocity [EDV], and CA or SMA/aortic systolic ratios) for detecting >=50% and >=70% ISS. These were compared to duplex velocities obtained from 97 native CAs and 74 native SMAs with >=50% stenosis done in the same study period. RESULTS: The mean stented celiac PSV (cm/s), EDV, and systolic ratio for >=50% ISS were 447, 136, and 7.1 vs 379, 104, and 5.2 for >=50% native stenosis (P = .067, .106, and < .01). The mean stented SMA PSV, EDV, and ratio for >=50% ISS were 410, 114, and 6.2 vs 405, 76, and 2.0 for >=50% native stenosis (P = .885, .037, and < .0001). The PSV cutpoints for detecting >=50% SMA ISS was 325 cm/s (sensitivity 89%, specificity 100%, and overall accuracy 91%) vs 295 cm/s for >=50% native SMA and for >=70% SMA ISS was 412 (sensitivity 100%, specificity 95%, and overall accuracy 97%) vs 400 for native stenosis. The PSV cutpoints for >=50% CA ISS was 274 cm/s (sensitivity 96%, specificity 86%, and overall accuracy 93%) vs 240 cm/s for >=50% native stenosis and for >=70% CA ISS was 363 (sensitivity 88%, specificity 92%, and overall accuracy 90%) vs 320 cm/s for native stenosis (sensitivity 80, specificity 89%, and overall accuracy 85%). ROC analysis also showed that both PSVs and EDVs were equal predictors for SMA and CA >=50% and >=70% ISS. For >=50% SMA ISS, the area under the curve (AUC) for PSV equals 0.91, EDV = 0.81, P = .341. For CA, PSV, AUC = 0.99, EDV = 0.88, P = .063. CONCLUSIONS: There is a tendency toward higher velocities in stented CA/SMAs in comparison to native arteries. Caution must be exercised in using duplex velocity cutoffs for native CA/SMA stenosis for stented CA/SMA. Further prospective validation studies are needed. PMID- 22301213 TI - Design and synthesis of 5-(substituted benzylidene)thiazolidine-2,4-dione derivatives as novel tyrosinase inhibitors. AB - In continuing our search for novel tyrosinase inhibitors, a series of 5 (substituted benzylidene)thiazolidine-2,4-diones were rationally designed and synthesized, and their inhibitory effects on mushroom tyrosinase activity were evaluated. Twelve target compounds 2a-2l were designed and synthesized based on the structural characteristics of N-phenylthiourea, a tyrosinase inhibitor, and tyrosine and L-DOPA, the natural substrates of tyrosinase. Among them, (Z)-5-(4 hydroxybenzylidene)thiazolidine-2,4-dione (2a) and (Z)-5-(3-hydroxy-4 methoxybenzylidene)thiazolidine-2,4-dione (2f) exhibited much higher tyrosinase inhibitory activities, with IC(50) values of 13.36 and 9.87 MUM, respectively, than kojic acid (IC(50) = 24.72 MUM). Kinetic analysis of tyrosinase inhibition revealed that 2a and 2f are competitive inhibitors of mushroom tyrosinase. In addition, through prediction of the potato catechol oxidase tertiary structure and simulation of docking with compounds 2a and 2f using DOCK6, we found that these inhibitors likely bind to the active site of the enzyme. Docking simulation results suggested that 2a and 2f have high binding affinities with potato catechol oxidase. In addition, compounds 2a and 2f effectively inhibited tyrosinase activity and reduced melanin levels in B16 cells treated with alpha melanocyte-stimulating hormone (alpha-MSH). These data strongly suggest that compounds 2a and 2f suppress the production of melanin via the inhibition of tyrosinase activity. PMID- 22301214 TI - Design, synthesis and pharmacological evaluation of new series of naphthalenic analogues as melatoninergic (MT1/MT2) and serotoninergic 5-HT2C dual ligands (I). AB - As part of our ongoing interest in developing new melatoninergic ligands bearing the same pharmacological profile as agomelatine, we focused our attention on this compound as a lead. Several chemical modifications have been performed on positions C-3 and 8 of the naphthalene ring determined as primary targets for the agomelatine metabolism. Herein we report the modulation of the positions C-3 and 7 in addition of the amide side chain because of this later prominent role in the affinity profile of such ligands. Synthesized compounds were then biologically evaluated at human cloned melatoninergic and serotoninergic receptors and showed different binding affinity and intrinsic activity profiles. Compounds bearing fluoroacetamide group (compounds 4 and 5) showed a high melatoninergic binding affinity particularly towards MT(1) receptor subtype. Thus, the fluoroacetamide 4 exhibited a good melatoninergic (MT(1)/MT(2)) binding affinity (70 pM) higher than the lead. Moreover, other compounds (10a, 10e, 16, 17 and 18) issued from these modulations behaved as MT(1) and MT(2) agonists and exhibited a sub nanomolar binding affinity towards these receptors. However, only compounds 10e, 17 and 18 showed a sub-nanomolar binding affinity at 5-HT(2C) higher than the agomelatine. PMID- 22301215 TI - 1,4-diarylpiperazines and analogs as anti-tubercular agents: synthesis and biological evaluation. AB - Despite progress in modern chemotherapy to combat tuberculosis, the causative pathogen Mycobacterium tuberculosis (M.tb.) is far from eradicated. Bacillary resistance to anti-mycobacterial agents, bacillary persistence and human immunodeficiency virus (HIV) co-infection hamper current drug treatment to completely cure the infection, generating a constant demand for novel drug candidates to tackle these problems. A small library of novel heterocyclic compounds was screened in a rapid luminometric in vitro assay against the laboratory M.tb. strain H37Rv. A group of amidines was found to have the highest potency and was further evaluated for acute toxicity against C3A hepatocytes. Next, the most promising compounds were evaluated for activity against a multi drug resistant clinical isolate. The group of amidines was also tested for their ability to kill intracellular M.tb. residing in mouse J774A.1 macrophages. Finally, we report on a correlation between the structural differences of the compounds and their anti-mycobacterial activity. PMID- 22301216 TI - Structure-activity relationships of novel alkylides: 3-O-arylalkyl clarithromycin derivatives with improved antibacterial activities. AB - A series of novel alkylides, possessing 3-O-arylalkyl group instead of 3-O cladinose, were designed, synthesized and evaluated for in vitro antibacterial activities. The increased potency clearly ranked by the order of 3-O-(3-aryl-2 propargyl), 3-O-(3-aryl-E-prop-2-enyl), 3-O-(3-aryl-propyl), and 3-O-(3-aryl-Z prop-1-enyl) groups. Some alkylides, exemplified by 7a, 10a, 21, 22, 26, 27 and 33, showed improved activities against inducible MLS(B) resistance and efflux resistance compared to the second-generation macrolides. Among them, 26 possessed comparable activities against erythromycin-susceptible Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes (MICs of 0.016-0.5 MUg/mL). Moreover, 26 displayed dramatically enhanced potency against both efflux resistant and inducibly MLS(B) resistant strains (MICs of 0.125-0.5 MUg/mL) resistant to clarithromycin and azithromycin (MICs of 1- >254 MUg/mL), independent of methicillin-susceptible and methicillin-resistant phenotypes. PMID- 22301217 TI - High-resolution melting and real-time PCR for quantification and detection of drug-resistant HBV mutants in a single amplicon. AB - BACKGROUND: Antiviral therapy by nucleoside/nucleotide analogues (NAs) effectively reduces HBV replication in chronic hepatitis B (CHB) patients. Because long-term NA treatments will eventually select for drug-resistant mutants, early detection of mutants and frequent monitoring of viral loads is crucial for successful NA therapy. Because no efficient test for one-tube quantification and qualification of various HBV-resistant mutants exists, we propose to use high-resolution melting (HRM) analysis in combination with real time PCR to achieve this unmet need. METHODS: We developed a single amplicon for detecting HBV mutants resistant to lamivudine (LMV), adefovir (ADV) and entecavir (ETV), which are commonly used for CHB treatment. Our design consists of two steps: real-time PCR for viral quantification, and hybridization probe HRM analysis for detection of specific drug-resistant mutants. RESULTS: Assay quantification was accurate (R=0.98) for viral loads from 10(3) to 10(9) copies/ml. HRM analysis produced distinct melting temperatures that clearly distinguished the mutants, rtM204V/I (LMV), rtA181V and rtN236T (ADV), and rtT184G and rtM250V (ETV), from their respective wild types. The assay detected mutants at only 10-25% of the HBV population. The clinical applicability of this assay was tested in a pilot study with serial samples from patients receiving LMV treatment. CONCLUSIONS: Flexibility, speed and cost-efficiency are additional benefits unique to our assay. The clinical sample results further support the feasibility of applying our design to frequent and long-term monitoring of CHB patients receiving NA treatments in the clinical setting. PMID- 22301218 TI - Initial management and classification of pelvic fractures. AB - Pelvic fractures represent a significant transfer of kinetic energy to the body, and more than 80% of patients with unstable pelvic fractures have additional musculoskeletal injuries. A systematic approach with prompt intervention is critical in the initial management of patients with pelvic fractures. If intra abdominal bleeding is suspected, diagnostic peritoneal lavage, focused assessment with sonography for trauma, or a CT examination is usually performed. CT angiography and interventional radiographic angiography are useful tools for determining the location of bleeding and the amount of blood loss. Patients presenting in extremis should undergo immediate pelvic stabilization and laparotomy with pelvic packing if indicated. Stable patients can undergo CT angiography. If a large pelvic hematoma or contrast blush is present, extraperitoneal packing or angiography can be performed based on the availability of the needed subspecialists. The orthopaedic surgeon provides prompt stabilization using external immobilizers, external fixation, or traction. The bladder, urethra, and nerve roots have an intimate location within the pelvis and are predisposed to injury in patients with pelvic fractures. Appropriately identifying associated abdominal, urologic, or neurologic injuries will provide important opportunities to reduce patient morbidity and improve long-term outcomes. PMID- 22301219 TI - Techniques of anterior pelvic fixation. AB - Although definitive fixation of anterior pelvic ring injuries is usually referred to an orthopaedic trauma surgeon or a surgeon proficient in pelvic surgery, all orthopaedic surgeons should be familiar with the initial management and resuscitation of patients with high-energy pelvic ring injuries. The initial treatment may be limited to sheet or binder application in the emergency department to allow transfer of the patient to a trauma center or the application of an external fixator by an on-call surgeon, even though that surgeon may not be responsible for definitive fixation. It is important to understand the general principles and approaches used at the time of definitive surgery because decisions made by the initial treating physician may affect (or limit) the ability of the orthopaedic traumatologist to provide definitive care. PMID- 22301220 TI - Posterior pelvic ring injuries: when to perform open reduction and internal fixation. AB - Unstable posterior pelvic ring injuries are commonly treated with percutaneous iliosacral screw fixation. Despite the efficiency of the minimally invasive technique, complications and failures occur. To maximize reduction quality and fixation stability, open techniques for pelvic ring fixation exist. Timing, approaches, clamp positioning, and implant options determine the effectiveness of the open techniques. PMID- 22301221 TI - Surgical techniques for complex proximal tibial fractures. AB - In managing complex proximal tibia fractures, several options are available to the treating surgeon. Closed management with or without external fixation, formal open reduction and internal fixation, and intramedullary nail fixation have been described in the literature. There is a lack of consensus regarding the optimal treatment method for complex bicondylar patterns or proximal metadiaphyseal fractures with or without involvement of the articular surface. It is helpful to review the standard and alternative surgical approaches to bicondylar tibial plateau fractures and to be aware of the intramedullary nail as an alternative approach for complex proximal metadiaphyseal patterns. PMID- 22301222 TI - Staged treatment and associated complications of pilon fractures. AB - Historically, the treatment and outcomes related to pilon fractures have been variable despite anatomic reduction and fixation. Early results with treatment via early primary open reduction and internal fixation yielded mixed clinical outcomes, especially suboptimal complication rates, including infection, malunion, and nonunion. Treatment with external fixation also exhibited similar outcomes with mixed support reported in the literature. Despite continued controversy, the advent of newer implant technologies, improved surgical techniques, and management with a staged protocol have resulted in encouraging clinical outcomes with minimization of postoperative complications. Crucial decisions made during treatment can help to maximize outcomes while minimizing complication rates. Particular attention to the fracture pattern with radiographic guidance can help direct surgical decision making with appropriate care given to optimize soft-tissue status. A variety of available incisions can facilitate proper bony and articular reduction. During the late and failed stages of fracture management, additional treatment options include external ring fixation, arthrodesis, and arthroplasty. As complications arise, meticulous, prompt care can help to achieve the best possible outcomes. PMID- 22301223 TI - Scaphoid fractures: what's hot, what's not. AB - The scaphoid is the most commonly fractured carpal bone of the wrist. It is an unusual carpal bone in that it bridges both the proximal and the distal rows; this subjects it to continuous shearing and bending forces. Approximately 80% of the scaphoid is covered by cartilage, which limits its ligamentous attachment and vascular supply. Most scaphoid fractures occur at the waist. Acute stable fractures or incomplete fractures of the scaphoid may be treated nonsurgically; a high rate of union can be expected. However, there is considerable debate about the type of immobilization needed. Although closed treatment of stable wrist fractures of the scaphoid achieve a high rate of healing, prolonged cast immobilization may lead to complications, including muscle atrophy, possible joint contracture, and disuse osteopenia. Because of this, internal fixation of minimally displaced fractures of the scaphoid has recently become popular. There is consensus in the literature that nonunion of the scaphoid and proximal pole fractures should be treated surgically. In the past several decades, percutaneous arthroscopic techniques of scaphoid stabilization, which minimize surgical morbidity, have become popular. There also has been a significant improvement in the management of difficult scaphoid nonunions, with or without deformity. Improved techniques include open and dorsal approaches and vascularized bone grafting of resistant scaphoid nonunions. Declining in popularity is the prolonged immobilization of unstable fractures when surgical stabilization may have been a better treatment option. PMID- 22301224 TI - Surgical anatomy of the shoulder. AB - The glenohumeral articulation is a versatile joint that requires a complex integration of bony ligamentous, musculotendinous, and neurovascular structures for proper function. Injuries resulting from dysfunction are common and potentially debilitating. Many of these injuries can be managed nonsurgically; however, if surgical treatment is indicated, a thorough knowledge of the anatomy of the shoulder girdle is critical. It is important for the surgeon to be aware of commonly used arthroscopic and surgical approaches to the glenohumeral joint along with anatomic structures at risk with each surgical approach and methods of avoiding injury. PMID- 22301225 TI - Decision making in massive rotator cuff tears. AB - Although many definitions have been used to define massive rotator cuff tears, a tear is generally considered massive if it is greater than 5 cm in diameter. Most massive rotator cuff tears are chronic, and patients commonly present with an insidious onset of gradually worsening pain and weakness in the involved shoulder. In rare situations, patients without preexisting rotator cuff disease may experience an acute injury and present with a massive rotator cuff tear. A thorough history and physical examination is important to establish the diagnosis and determine the most appropriate treatment. Because most massive rotator cuff tears are chronic in nature, the quality of the underlying rotator cuff tissue is often poor, making repair difficult. Other treatment options include physical therapy, biceps tenotomy or tenodesis, suprascapular nerve release, rotator cuff repair with tissue augmentation, tendon transfer, and reconstruction with hemiarthroplasty or reverse shoulder arthroplasty. Integrating findings from the history, physical examination, and diagnostic imaging is the basis of clinical decision making. PMID- 22301226 TI - The role of the biceps tendon in massive rotator cuff tears. AB - Tendinopathy of the long head of the biceps (LHB) tendon commonly occurs in patients with rotator cuff tears, and the inflammation of one head tends to lead to inflammation of the other. Many theories have been proposed regarding the function of the LHB tendon; however, its exact purpose is poorly understood. It has been described as an important stabilizer of the glenohumeral joint, a depressor of the humeral head, and as a vestigial structure. The LHB tendon can be a significant source of pain in patients with rotator cuff tears. The appropriate treatment depends on the patient's age, comorbidities, activity level, extent of disability, the presence of rotator cuff arthropathy, and the quality of the rotator cuff tissue. Conservative treatment is usually attempted first, with modalities such as nonsteroidal anti-inflammatory drugs, corticosteroid injections, physical therapy, and activity modification. If symptoms persist, biceps tenotomy or tenodesis may be combined with rotator cuff repair, depending on the quality of the rotator cuff tissue, the severity of rotator cuff arthropathy, and the willingness of the patient to comply with postoperative immobilization and rehabilitation. Even when rotator cuff repair is not possible, isolated tenotomy or tenodesis of the LHB tendon can provide substantial pain relief. PMID- 22301227 TI - Arthroscopic repair techniques for massive rotator cuff tears. AB - Patients with massive rotator cuff tears present with pain, weakness, and loss of function. Candidates for arthroscopic repair include symptomatic, young, active patients; those with an acute tear or tears with early changes of atrophy; and patients willing to comply with recovery and rehabilitation processes after surgery. As massive rotator cuff tears extend, the glenohumeral articulation is destabilized, allowing superior migration. Repair of the force couples and reinforcement of the anterosuperior rotator cuff cable can restore functional elevation via the deltoid. Muscle changes, including rotator cuff atrophy and fatty infiltration, will affect shoulder strength and function. As chronic changes become more extensive (such as the absence of the acromiohumeral interval and degenerative joint changes), other repair options may be more durable. Other arthroscopic options, including partial rotator cuff closure, graft to augment the repair, and use of the long head of the biceps tendon, have been helpful in pain relief and functional gains. PMID- 22301228 TI - How to minimize complications in shoulder instability and rotator cuff surgery. AB - Arthroscopic instability and rotator cuff repair techniques have rapidly evolved over the past decade with expanding indications; however, there has been a corresponding increase in complications. Careful attention to detail and patient selection will result in satisfactory outcomes for most patients. PMID- 22301229 TI - Massive rotator cuff tears without arthropathy: when to consider reverse shoulder arthroplasty. AB - Massive rotator cuff tears often present a challenge for the treating orthopaedic surgeon. A multitude of surgical approaches have been described to manage this condition, ranging from biceps tenotomy to complex muscle transfers to reverse shoulder arthroplasty. Among these procedures, reverse shoulder arthroplasty is increasingly advocated to relieve pain and restore function; however, the exact role of this arthroplasty procedure continues to be defined, particularly in patients without any evidence of associated glenohumeral arthritis. In this patient population, the reverse shoulder prosthesis is used primarily to address the instability associated with massive rotator cuff tears, as opposed to the more common application of arthroplasty to manage cartilage disease. Currently accepted indications for reverse shoulder arthroplasty include patients with pseudoparalysis and irreparable rotator cuff tears, with or without anterosuperior escape. Surgeons must be aware of conditions that may clinically mimic pseudoparalysis caused by a rotator cuff tear, such as axillary nerve injury, deltoid dehiscence, or cervical radiculopathy. These conditions produce deltoid insufficiency and are unlikely to benefit from a reverse shoulder arthroplasty. Caution is also warranted when considering this procedure in patients with massive rotator cuff tears in whom active forward elevation greater than 90 degrees is preserved. These patients may achieve little benefit in range of motion and pain relief with a reverse shoulder arthroplasty. PMID- 22301230 TI - Complications of the reverse prosthesis: prevention and treatment. AB - Reverse total shoulder arthroplasty was developed in the late 1980s for elderly patients with rotator cuff arthropathy. Several biomechanical advantages of the reverse shoulder arthroplasty result in improved deltoid function, which improves shoulder motion and function compared to other types of shoulder arthroplasty. The main indication for the reverse prosthesis is painful rotator cuff tear arthropathy. The indications for reverse shoulder arthroplasty have continued to expand since it was first performed in the United States in 2004. Although the results of reverse total shoulder arthroplasty have been generally favorable, the complication rate is higher than that of conventional total shoulder arthroplasty. Complications include those common to other shoulder procedures (infection, instability, and nerve injury) and those unique to reverse total shoulder arthroplasty (scapular notching, glenoid baseplate failure, component disassociation, and scapular stress fractures). It is helpful for orthopaedic surgeons to understand ways to avoid these complications and methods with which to treat them. PMID- 22301231 TI - How to minimize complications in acromioclavicular joint and clavicle surgery. AB - Up to 50% of all athletic shoulder injuries are acromioclavicular joint separations. The ideal treatment for type III injuries remains controversial. Current reconstruction techniques include anatomic coracoclavicular reconstructions and newly developed arthroscopic techniques. Clavicle fractures have traditionally been treated nonsurgically based largely on early reports of surgical complications, but there has been a dramatic surge in the surgical treatment of clavicle fractures over the past 5 years because of recent reports of poorer outcomes with nonsurgical management. PMID- 22301232 TI - MRI and arthroscopy correlations of the shoulder: a case-based approach. AB - Over the past three decades, shoulder arthroscopy and MRI have seen significant advancements. Initially, distinguishing between normal and pathologic anatomy was one of the greatest challenges. Radiologists and arthroscopic shoulder surgeons have provided feedback to each other based on their experiences with selected shared patients, thereby accelerating the understanding of the arthroscopic and MRI appearance of both normal and pathologic anatomy. This process has led to the current refined understanding of both the basics and subtleties of MRI and arthroscopy correlations in the shoulder. Using a case-based approach provides examples of the correlation between MRI and arthroscopic findings in selected shoulder conditions. PMID- 22301233 TI - Distal humeral fractures: role of internal fixation and elbow arthroplasty. AB - Fractures of the distal humerus can be challenging to treat. Advances in imaging, internal fixation, and arthroplasty have resulted in improved management of these injuries. Preoperative CT with three-dimensional reconstruction allows a better understanding of fracture patterns and helps the surgeon to select the best treatment options. Parallel plating techniques often provide stable internal fixation constructs, even in fractures with severe comminution. Precontoured periarticular plates facilitate internal fixation. More attention is now paid to recognizing and managing bone loss through metaphyseal shortening and/or bone grafting. Elbow arthroplasty appears to provide good early outcomes for elderly patients with severe elbow injury. Distal humeral hemiarthroplasty can be considered for elbow fractures with severe damage to the articular surface if the patient is too young and active to comply with the restrictions recommended after total elbow arthroplasty. Advances are still needed to reduce the overall complication rates associated with the treatment of distal humeral fractures. PMID- 22301234 TI - Ligament injury and the use of hinged external fixators at the elbow. AB - The indications and techniques for managing collateral ligament deficiencies after traumatic elbow injuries are continuing to evolve. Essentially, the lateral collateral ligament must be repaired, whereas the medial collateral ligament will heal in some instances. The repair of the medial collateral ligament is needed only in competitive athletes who place high valgus stress on the elbow joint. An understanding of the role of external fixators is also evolving. External fixation is effective in managing acute elbow trauma that results in an unstable elbow and reconstructive procedures in which the collateral ligaments or articular surface require protection in circumstances requiring movement of the elbow joint. Using half pins and a laterally placed external fixator provides the mechanical stability required in most traumatic settings. PMID- 22301235 TI - Complex fractures of the proximal ulna: the critical importance of the coronoid fragment. AB - Complex fractures of the proximal ulna with associated elbow instability represent challenging disorders with a high incidence of complications, including malunion, arthrosis, stiffness, and recurrent instability. If a significant coronoid fragment is present, there is an increased risk of a poor outcome. Proper management of this coronoid fragment can be critical to a successful outcome. Information on identifying, reducing, and fixing the coronoid fragment in complex proximal ulnar fractures will help the treating orthopaedic surgeon maximize results with this difficult injury pattern. PMID- 22301236 TI - MRI and arthroscopy correlations of the elbow: a case-based approach. AB - The number of elbow arthroscopies and indications for the procedure have increased significantly since the advent of modern elbow arthroscopy in the 1980s. In addition to the patient history, physical examination, and plain radiography, MRI is an important tool for the clinician in diagnosing several pathologies within and around the elbow. Understanding the pathophysiology and clinical presentation and being familiar with the MRI characteristics of a variety of elbow conditions will assist the physician in making an accurate diagnosis and help guide appropriate treatment. PMID- 22301237 TI - New frontiers in cartilage imaging of the hip. AB - High-resolution MRI for cartilage mapping is a rapidly evolving field that is contributing to a better understanding of osteoarthritis. The basic science of cartilage imaging uses different modalities (such as T1rho, T2 mapping, delayed gadolinium-enhanced MRI of cartilage) and has clinical applicability for treating hip disorders in the young adult. These imaging techniques rely on biomarkers to quantify early cartilage degeneration. The common biomarkers are proteoglycan concentration and collagen integrity. Imaging the hip presents unique challenges because of its sphericity, the close apposition of the two cartilage layers, and the limitations in using surface coils. PMID- 22301238 TI - Pathomorphology and treatment of femoroacetabular impingement. AB - Femoroacetabular impingement is recognized as a major cause of hip pain and early hip joint osteoarthritis in young adults. The dynamic conflict between the femoral neck and the acetabular rim has been shown to result in labral tears, cartilage lesions, and early osteoarthritis. To be successful, the treatment strategy should address the underlying pathomorphology at the femoral neck, the acetabulum, or both. An overview of the various pathomorphologies leading to femoroacetabular impingement and a treatment algorithm intended to preserve the native hip joint should be helpful to the orthopaedic surgeon treating patients with this condition. PMID- 22301239 TI - Open surgical dislocation for the treatment of femoroacetabular impingement: past, present, and future. AB - Femoroacetabular impingement results from a lack of clearance between the femoral neck and the acetabulum. This condition is most commonly seen in the young adult presenting with hip pain after activity. There have been rapid advancements in the understanding of femoroacetabular impingement to include diagnostic, imaging, and treatment options. An open surgical dislocation approach has been developed that offers a safe and effective method to dislocate the hip and allow direct visualization and full access to treat the often complex intra-articular pathologies of femoroacetabular impingement. The ultimate goal of treatment in carefully selected patients is relief of hip pain and preservation of the hip joint. PMID- 22301240 TI - Arthroscopic management of hip pathomorphology. AB - The role for the arthroscopic correction of femoroacetabular impingement continues to evolve. As the understanding of hip pathomorphology improves and arthroscopic techniques for managing these disorders advance, the indications for arthroscopic femoroacetabular correction become clearer. Attention to detail with respect to diagnoses and surgical management is critical to optimize outcomes in this patient population. Studies have shown comparable outcomes for arthroscopic management and open surgical techniques. Further study is required to better define the role for arthroscopic versus open surgical management of selected pathomorphologies of the hip. PMID- 22301241 TI - Approaches for revision total hip replacement. AB - Choosing the approach for revision total hip replacement is an essential part of surgical planning and should be done well before the patient enters the operating room. Planning includes selecting patient positioning, the location of the incision, techniques for managing previous incisions, the needed exposure equipment, and the steps needed to extend the exposure. More extensive exposure on both the acetabular and femoral sides is often required in revision surgery. PMID- 22301242 TI - How to do a revision total hip arthroplasty: revision of the acetabulum. AB - The need for revision total hip arthroplasty continues to increase as the indications for total hip replacement broaden and the average life expectancy of patients and their demands for activity increase. To achieve a successful long term outcome after revision acetabular surgery, the surgical reconstruction must provide a mechanically stable construct that will minimize micromotion, allow bone ingrowth, and restore appropriate hip biomechanics. Achieving these goals during revision acetabular surgery can be challenging because of periacetabular bone loss and a compromised biologic environment. Acetabular classifications can help to preoperatively predict areas of bone loss to guide treatment options. Most acetabular defects can be managed with a hemispheric or elliptic porous acetabular component; however, large areas of segmental or cavitary bone loss may require alternative treatments such as custom implants, metal/allograft augmentation, or an acetabular cage reconstruction. PMID- 22301243 TI - Femoral fixation in revision total hip arthroplasty. AB - Management of the femur during revision total hip arthroplasty can be challenging. Strategies for femoral reconstruction are based on understanding the degree of femoral bone loss. Numerous options exist for femoral reconstruction depending on the quantity and quality of the remaining femoral bone stock, including cemented fixation, cementless fixation using proximally porous-coated implants, cylindrical extensively porous-coated implants, modular and nonmodular tapered fluted stems, impaction bone grafting, allograft-prosthetic composites, and proximal femoral replacements (megaprostheses). An understanding of the results of various methods of femoral reconstruction is helpful in guiding the revision surgeon faced with a challenging femoral revision. PMID- 22301244 TI - MRI and arthroscopy correlations of the hip: a case-based approach. AB - Disorders of the hip joint can be physically disabling for the patient and a diagnostic challenge for the physician. Advances in imaging the hip with MRI can help the physician determine a more specific diagnosis for patients with acute or chronic hip pain. MRI and particularly magnetic resonance arthrography have helped raised awareness of nonarthritic hip problems and have made the diagnosis of hip problems much easier. Intra-articular and extra-articular processes can be evaluated with MRI; multiple sequences are available to increase the sensitivity and specificity for detecting specific pathology around the hip. Because the hip is a deep joint within a large soft-tissue envelope, MRI more precisely delineates the sources of hip pain by evaluating the soft tissues and ligamentous structures around the hip. It is helpful to understand the role of MRI in evaluating common pathologic conditions within the hip joint, including labral tears, chondral lesions, loose bodies, tears of the ligamentum teres, femoral acetabular impingement, developmental dysplasia of the hip, and pigmented villonodular synovitis. Hip arthroscopy, a less invasive technique for treating hip problems, has also contributed to the rapid growth of interest in this area of orthopaedic surgery. Hip arthroscopy can be used to evaluate disorders in the intra-articular region (central and peripheral compartments) and periarticular region (iliopsoas bursa and tendon disorders) as well as those in the peritrochanteric region. PMID- 22301245 TI - Current controversies in partial knee arthroplasty. AB - Partial knee arthroplasty has enjoyed renewed interest during the past decade. It is helpful to be familiar with the classic and current indications, contraindications, and technical aspects of partial knee arthroplasty, including patellofemoral, medial unicompartmental, and lateral unicompartmental knee arthroplasty. Various implant choices for partial knee arthroplasty can be compared and evaluated based on patient characteristics, design qualities, and reported outcomes. It is also helpful to review the indications and techniques for performing medial or lateral unicompartmental knee arthroplasty in combination with arthroscopically assisted reconstruction of the anterior cruciate ligament. PMID- 22301246 TI - Current and innovative pain management techniques in total knee arthroplasty. AB - Pain management is a major concern for patients contemplating total knee replacement surgery and is one of the leading causes of dissatisfaction after knee replacement. Substantial progress has been made over the past several years in improving pain control after total knee replacement using multimodal pain control, preemptive analgesia, and periarticular injections. PMID- 22301247 TI - Multimodal pain management with peripheral nerve blocks for total knee arthroplasty. AB - Multimodal pain management techniques using femoral and sciatic nerve blocks can dramatically improve a patient's experience after total knee arthroplasty. Nerve blocks reduce postoperative pain and the need for parenteral opioids and result in fewer medical complications associated with opioid use. Peripheral nerve blocks have traditionally been underutilized in lower extremity surgery; however, more modern techniques now allow for safe, efficient, and reliable femoral and sciatic blocks. Peripheral nerve blocks are now routinely used in both primary and revision total knee arthroplasty. Although it is difficult to isolate the added benefit of sciatic nerve blocks, there is a growing body of evidence for using femoral and/or sciatic nerve blocks as part of a multimodal approach to pain management. With many years of experience and published results on thousands of patients, it is clear that the risks of peripheral nerve blocks are minimal, whereas the benefits are substantial. PMID- 22301248 TI - Complications after total knee arthroplasty: how to manage patients with osteolysis. AB - Total knee arthroplasty generally is a highly successful orthopaedic procedure, but mechanical failure sometimes occurs. Debris particles, especially from polyethylene, can affect the long-term durability of the implant. Revision total knee arthroplasty is complex, and preoperative planning must consider alignment, stability, fixation, and knee motion. The reason for failure must be identified before complex reconstruction in the presence of osteolysis, and the procedure must appropriately augment the defective bone and place a stable, well-fixed implant. PMID- 22301249 TI - Evaluation and management of complications of the extensor mechanism. AB - Extensor mechanism and patellofemoral joint complications occur infrequently following total knee arthroplasty but represent a high percentage of clinically significant problems. Accurately diagnosing and identifying specific complications of the underlying etiology are the keys to successful treatment. Patellofemoral joint complications may be broadly categorized into implant related problems, tendinous and patellar bone integrity issues, and soft-tissue imbalance or instability of the patellofemoral joint. It is also important to be aware of issues surrounding implant selection, surgical technique, and the available treatment options for patellofemoral joint complications. PMID- 22301250 TI - Infection following total knee arthroplasty: prevention and management. AB - Despite diligent efforts to prevent infection, prosthetic knee infection occurs in up to 2% of patients treated with total knee arthroplasty. Although the risk of infection is relatively low, the effects are considerable. The number of total knee arthroplasties is projected to increase by more than 600% by 2030, resulting in 3.48 million knee replacements, with a possible 70,000 prosthetic knee infections. Infection will be the most common indication for revision total knee arthroplasty. Prophylactic antibiotics and minimizing patient risk factors are critical in preventing infections. Staphylococcus is the most common organism in infected total knee arthroplasties. Prompt diagnosis and treatment are crucial to the long-term outcomes of patients with prosthetic joint infections. The erythrocyte sedimentation rate, C-reactive protein level, and interleukin-6 serum level should be checked in all patients with clinical signs of infection or unexplained pain or stiffness. The surgical management of a prosthetic knee infection depends on several factors, but none is more important than the timing of infection in relationship to the index surgery. With a success rate of 80% to 90%, two-stage component exchange remains the treatment of choice for chronically infected total knee arthroplasties. PMID- 22301251 TI - Charcot foot: a surgical algorithm. AB - The historic treatment of Charcot foot has entailed non-weight-bearing immobilization during the acute active phase, followed by longitudinal management with accommodative bracing. This treatment plan yields poor outcomes, even in cases classified as successful. An appreciation of poor outcomes convinced experts to attempt correction of the resultant deformities. Early attempts at surgical correction of the acquired deformities in patients with medical comorbidities were complicated by infection, wound failure, and mechanical loss of correction. New surgical techniques have been designed to obtain and maintain correction and minimize the risks for complications and poor outcomes in this complex patient population. PMID- 22301252 TI - Advanced techniques in cervical spine surgery. AB - Many disorders of the cervical spine can be effectively treated through a posterior approach. Generally, posterior decompressions such as a laminectomies, laminoplasties, and/or foraminotomies result in fewer postoperative complications compared with anterior approaches for multilevel surgery. Complications can include dysphagia, dysphonia, and pseudarthrosis. Fusion is indicated in spinal conditions that involve cervical instability, subluxation, or severe sagittal imbalance. During the past decade, techniques have been developed for instrumentation of the upper and subaxial cervical spine. Several recent studies have led to a better understanding of the cervical spine anatomy, which has helped limit complications and facilitate surgical procedures. PMID- 22301253 TI - Cervical spine surgery: anterior microsurgery. AB - Anterior cervical decompression and fusion is one of the most commonly used procedures to treat myelopathy and radiculopathy. With the addition of the surgical microscope, enhanced visualization of the microanatomy has allowed the safe and efficient treatment of compressive pathology. It is important to understand the critical steps required to successfully treat cervical spine pathology from an anterior approach with the assistance of a surgical microscope, the factors involved in choosing a decompressive method, the technical considerations for intervertebral grafting, and the use of cervical plating. The knowledge of surgical pearls may optimize spinal cord and nerve root decompression, increase fusion rates, and give patients the best chance for a successful clinical outcome. PMID- 22301254 TI - Cervical spine surgery: cervical laminaplasty. AB - Multilevel cervical spondylosis resulting in myelopathy is a complex condition to treat surgically. Several anterior and posterior procedures have been described. Cervical laminaplasty is a procedure that provides multilevel posterior cord decompression while attempting to eliminate the postoperative development of instability and kyphosis by retaining the posterior elements. Because laminaplasty does not involve arthrodesis, more postoperative motion is preserved and early range of motion is encouraged to avoid stiffness. Although laminaplasty is a relatively straightforward procedure, understanding several key points can help avoid common technical challenges and ensure the best possible outcomes for patients. A variety of fixation techniques, each with advantages and limitations, are available to keep the laminaplasty door open. The surgeon should be aware of the complications associated with cervical laminaplasty. PMID- 22301255 TI - Patient evaluation and clinical assessment of adult spinal deformity. AB - The clinical evaluation of adults with spinal deformity can be challenging for both general orthopaedic surgeons and spinal specialists. To properly treat these patients, the physician must be aware of the various types of adult spinal deformity and the basic principles of spinal misalignment. A complete patient assessment must include a thorough history and physical examination. Appropriate imaging studies can be used to characterize the extent of the deformity and determine the need for surgical intervention or referral to a spine specialist. The ultimate goal of the evaluation of an adult with spinal deformity is to determine the impact of the deformity on the patient's quality of life, including the ability to work and perform activities of daily living. For patients considering surgical treatment, additional factors must be included in the assessment because of the high rate of complications associated with adult deformity procedures. PMID- 22301256 TI - Pediatric spinal deformity: what every orthopaedic surgeon needs to know. AB - Pediatric spinal deformity is an integral part of orthopaedic surgical practice. In a general or specialized practice, the well-versed orthopaedic surgeon should be aware of the diagnostic methods and the natural history from which practice standards are derived. It is important to be aware of the spectrum of spinal deformity in children (from early-onset scoliosis to adolescent idiopathic scoliosis, kyphosis, and spondylolisthesis) and current principles of growth and maturation as applied to the spine and the thorax. This information should be helpful in attaining the appropriate diagnosis, treatment, and/or referral for a pediatric patient with a spinal deformity. PMID- 22301257 TI - Spine problems in young athletes. AB - As the number of young people involved in sports activities increases, acute and chronic back pain has become more common. With a careful medical history and physical examination, along with the judicious use of imaging modalities, the causes of back pain can be correctly diagnosed and treated so that young athletes can quickly return to sports participation. Although most back pain in these young patients is muscular in origin, findings that should trigger increased concern include night pain, marked hamstring tightness, pain with lumbar spine hyperextension, or any neurologic finding. When recently developed vague back pain is present, a delay in radiographic imaging is warranted. With new back pain after trauma, AP and lateral radiographs of the symptomatic spinal area are indicated. CT, bone scans, and MRI should be reserved for special circumstances. Spondylolysis is the most common bony cause of back pain in young athletes. Spondylolysis can be treated with activity limitation, a specific exercise program, a thoracolumbar orthosis, and/or surgery. Treatment should be based on the amount of pain as well as the desire of the young athlete to continue in the sports activity that caused the pain. Other significant causes of back pain that require more extensive treatment in these young athletes include spondylolisthesis, lumbar disk disorders, and sacral stress fractures. It is anticipated that nearly all young athletes can return to sports activity after successful treatment. Even if surgical treatment is needed, return to all sports is expected, with the occasional exception of collision sports. PMID- 22301258 TI - Diagnosis and management of patients with instability of the knee. AB - Instability of a total knee arthroplasty is a fundamentally different problem from instability of the knee without an arthroplasty. Revision surgery to correct the inciting forces will usually be necessary, and ligament reconstruction alone is usually unsuccessful. Because it may be the presenting complaint for any of the usual conditions that require revision arthroplasty, instability as reported by a patient should be considered a symptom that requires detailed evaluation rather than immediate surgery. Evaluation should be systematic and comprehensive, meaning that the same algorithm or system should be applied to all knee arthroplasties, and all diagnostic entities should be considered. There are several common types of instability, each requiring a different surgical strategy. Any dysfunction of the extensor mechanism, including pain inhibition (even from the ipsilateral hip) may result in buckling. Structural recurvatum, often originating from relative quadriceps weakness, may require arthrodesis if extensor function is completely absent. Varus or valgus instability will require stabilization in the form of constrained implants, with or without ligament releases, advancements, or substitution. Realignment will almost always be advantageous. Flexion instability is invariably linked to flexion gaps that are larger or more lax than the extension gap, requiring revision with attention to gap balance, and in many cases, some degree of mechanically constrained devices. Arthritic knee joints in obese patients and those with severe angular deformity or fixed flexion contractures are at particular risk for instability after total knee arthroplasty. Instability that becomes apparent intraoperatively is a challenging condition, particularly when there is no immediate recourse to using constrained implants. PMID- 22301259 TI - MRI-arthroscopy correlation: the knee. AB - MRI findings can often be helpful in diagnosing and managing common knee injuries. The association between the normal and pathologic changes in the surgical anatomy of the knee commonly found on MRI and those found at arthroscopy can be demonstrated by examining a series of cases that correlate MRI and arthroscopy findings. Regular interactions are recommended between surgeons and musculoskeletal radiologists to improve MRI interpretation and achieve better surgical outcomes for patients. PMID- 22301260 TI - Imaging interpretation of oncologic musculoskeletal conditions. AB - There is considerable overlap in the clinical and imaging presentation of general orthopaedic conditions and musculoskeletal neoplasms. At centers that treat orthopaedic oncologic conditions, it is not uncommon to see patients with spine and extremity tumors previously treated for presumed general orthopaedic ailments. It is important for orthopaedic surgeons to understand how to interpret commonly ordered radiographic studies (radiographs, MRIs, and CT scans) as they relate to bone and soft-tissue tumors, to be familiar with the imaging appearance of common musculoskeletal lesions in the extremities and spine, and to understand what imaging findings should trigger a referral to an orthopaedic oncologist. PMID- 22301261 TI - Evaluation of the patient presenting with a malignant spinal tumor. AB - Malignant spinal tumors are frequently encountered in clinical practice. Most of these lesions are caused by metastatic or hematopoietic disease processes. It is useful for the practicing surgeon to have a framework for evaluating and treating these conditions. Equally important is the ability to recognize the rare patient who presents with a primary spinal malignancy, which requires a significantly different treatment protocol. PMID- 22301262 TI - Communication for all your patients. AB - Because communication is something that is often taken for granted, many people do not consciously think about communication habits and behaviors. When patients are questioned concerning important attributes of a doctor, they say they want someone who respects and listens to them. In a time of increasing malpractice litigation, physicians need to examine their communication skills. In an increasingly more diverse world, social and cultural beliefs, attitudes, and behaviors have a considerable effect on the health of communities. Patient safety, satisfaction, and successful outcomes rely on understanding the patient's medical and cultural needs. The concept of becoming a "cultural anthropologist" is improbable, but becoming aware of the demographics of the community in which the physician serves will improve communication and lead to improved patient and physician satisfaction, better patient compliance, and improved health outcomes. PMID- 22301263 TI - Practical research methods for orthopaedic surgeons. AB - Inherent to understanding an orthopaedic study is a fundamental knowledge of the study's design principles and statistics. Statistics, in part, allow a researcher to sample a portion of the population and use probability to decide whether the findings from the sample are likely to apply to the whole population. Although statistical jargon can be confusing, several simple principles guide the approach to research design. It is helpful for orthopaedic surgeons to review different study designs and their levels of evidence, to understand statistical jargon and the selection of the statistical test that is appropriate for given types of data, and to be familiar with the process of sample size calculations. Knowledge gained from statistical principles and research design is used to interpret study results. Such knowledge is invaluable for judging the value of new clinical evidence and for designing future studies. PMID- 22301264 TI - Maintenance of certification and keys to passing the recertification examination. AB - The American Board of Orthopaedic Surgery requires that each board-certified orthopaedic surgeon recertify every 10 years. This formal procedure of demonstrating competence as a surgeon, which used to be known as recertification, has been replaced by a more comprehensive process termed maintenance of certification (MOC). Even an experienced orthopaedic surgeon may find achieving MOC a daunting prospect. Simply preparing for and taking the recertification examination is an enormous challenge, but it is important to remember that the examination is merely one aspect of maintaining certification. Prior to sitting for the examination, each physician is required to complete the other MOC requirements, including amassing continuing medical education credits, compiling a case list, and soliciting peer recommendations. Familiarity with the MOC process, understanding the details of the examination, and proper preparation techniques will help orthopaedic surgeons gain insights into how to approach MOC. PMID- 22301265 TI - Real-world solutions for orthopaedic on-call problems. AB - An increasing percentage of emergency departments are reporting an inadequate number of on-call specialists. This situation is causing a growing crisis in emergency department on-call coverage for patients requiring orthopaedic care. Many orthopaedic surgeons are electing to opt out of emergency department on-call service. For many reasons, including a dwindling supply of eager participants, more medical groups are finding it difficult to fulfill their on-call obligations. This problem demands a variety of strategies to address the multiple causative factors that occur in practice settings. Initially, it may be necessary to incentivize on-call service so more surgeons are willing to participate. Incentives may include improving the group governance and bylaws to avoid confusion on the rules for providing on-call coverage. The on-call experience may require financial improvements, outsourcing with locum tenens, or a complete restructuring of the on-call arrangement with the formation of a hospitalist program. PMID- 22301266 TI - The evolution of MHC diversity: evidence of intralocus gene conversion and recombination in a single-locus system. AB - Gene conversion, the unidirectional exchange of genetic material between homologous sequences, is thought to strongly influence patterns of genetic diversity. The high diversity of major histocompatibility complex (MHC) genes in many species is thought to reflect a long history of gene conversion events both within and among loci. Theoretical work suggests that intra- and interlocus gene conversion leave characteristic signatures of nucleotide diversity, but empirical studies of MHC variation have rarely been able to analyze the effects of conversion events in isolation, due to the presence of multiple gene copies in most species. The potbellied seahorse (Hippocampus abdominalis), a species with a single copy of the MH class II beta-chain gene (MHIIb), provides an ideal system in which to explore predictions on the effects of intralocus gene conversion on patterns of genetic diversity. The genetic diversity of the MHIIb peptide binding region (PBR) is high in the seahorse, similar to other vertebrate species. In contrast, the remainder of the gene shows a total absence of synonymous variation and low levels of intronic sequence diversity, concentrated in 3 short repetitive regions and 1-12 SNPs per intron. The distribution of substitutions across the gene results in a patchwork pattern of shared polymorphism between otherwise divergent sequences. The pattern of nucleotide diversity observed in the seahorse MHIIb gene is congruent with theoretical expectations for intralocus gene conversion, indicating that this evolutionary mechanism has played an important role in MHC gene evolution, contributing to both the high diversity in the PBR and the low diversity outside this region. Neutral variation at this locus may be further reduced due to biases in nucleotide composition and functional constraints. PMID- 22301267 TI - C-reactive protein down-regulates endothelial nitric oxide synthase expression and promotes apoptosis in endothelial progenitor cells through receptor for advanced glycation end-products. AB - OBJECTIVE: C-reactive protein (CRP), the prototypic marker of inflammation, has been shown to be an independent predictor of atherosclerosis. CRP can regulate receptor for advanced glycation end-products (RAGE) expression in endothelial progenitor cells (EPCs). Endothelial nitric oxide synthase (eNOS) deficiency is a pivotal event in atherogenesis. It is believed that decreased eNOS bioactivity occurs early in atherogenesis. Therefore, we tested the hypothesis that CRP can alter eNOS expression and promote apoptosis in EPCs through RAGE. METHODS AND RESULTS: EPCs, isolated from bone marrow, were cultured in the presence or absence of LPS-free CRP (5, 10, 15, 20, and50MUg/ml). RAGE protein expression and siRNA were measured by flow cytometric analysis. PCR was used to detect eNOS mRNA expression. eNOS protein expression was measured by Western blot analysis. A spectrophotometer was used to assess eNOS activity. A modified Boyden's chamber was used to assess the migration of EPCs and the number of recultured EPCs was counted to measure adhesiveness. A MTT assay was used to determine proliferation. Apoptosis was evaluated by annexin V immunostaining and TUNEL staining. Co culturing with CRP caused a significant down-regulation of eNOS expression, inhibited the proliferation, migration, and adhesion of EPCs, and induced EPC apoptosis. In addition, these effects were attenuated during RAGE protein expression blockade by siRNA. CONCLUSIONS: CRP, at concentrations known to predict cardiovascular event, directly quenches the expression of eNOS and diminishes NO production, and may serve to impair EPC function and promote EPC apoptosis through RAGE. These data further support a direct role of CRP in the development and/or progression of atherosclerosis and indicate a new pathophysiologic mechanism of disturbed vascular adaptation in atherosclerosis. PMID- 22301268 TI - Analysis of the role of p38 MAP kinase in epidermal growth factor-induced JB6 Cl41 cell transformation by cDNA array. AB - To further explore the mechanism of p38 MAP kinase in regulation of JB6 Cl41 cell transformation. cDNA array was employed to scan the differential expression genes between DN-p38 cells and CMV-neo JB6 Cl41 cells after EGF stimuli. We found that up-expression genes including oncogenes and tumor suppressor genes, p53 associated protein, transcription repressors, apoptosis-associated genes, and growth arrest and DNA damage-inducible protein 153 were detected in DN-p38 cells, but low expression in CMV-neo JB6 Cl41 cells after EGF treatment. Meanwhile, some proto-oncogenes, such as c-Myc, and signal transducer and activator of transcription 1 (STAT1) were lowly expressed in EGF-stimulated DN-p38 cells, but had relatively high expression level in CMV-neo JB6 Cl41 cells under the same stimuli. Four of the differential expression genes were further confirmed by quantitative RT-PCR analysis. Our results indicate that p38 MAP kinase is involved in EGF-induced JB6 Cl41 cell transformation through effecting on more genes expression levels including transcription factors, proto-oncogene, apoptosis-related genes and growth arrest genes. PMID- 22301269 TI - Identification of ORF sequences and exercise-induced expression change in thoroughbred horse OXCT1 gene. AB - In the mitochondrial matrix, the OXCT1 gene catalyzes the reversible transfer of coenzyme A from succinyl-CoA to acetoacetate in a reaction related to energy production from ketone bodies. Here, horse OXCT1 gene containing coenzyme A transferase domain was identified in the transcriptome analysis of cDNAs derived from skeletal muscles. Horse OXCT1 gene consisted of 1761 [corrected] nucleotide sequences with an open reading frame of 1560 nucleotides encoding a protein of 520 putative amino acid residues.The number of non-synonymous substitutions was lower than the number of synonymous substitutions in the OXCT1 genes of other species, indicating that purifying selection occurred in the OXCT1 genes during evolutionary radiation. Quantitative real-time RT-RCR analysis showed a dominant expression pattern of horse OXCT1 gene in the cerebrum, heart, and skeletal muscle. Different expression levels of horse OXCT1 transcripts between before- and after-exercise samples were also measured in the skeletal muscles of six horses. These data could be of great use for further investigation of the relationship between energy products and horse OXCT1 gene. PMID- 22301270 TI - An enzyme-linked immunosorbent assay (ELISA) for quantification of human collectin 11 (CL-11, CL-K1). AB - Collectin 11 (CL-11), also referred to as collectin kidney 1 (CL-K1), is a pattern recognition molecule that belongs to the collectin group of proteins involved in innate immunity. It interacts with glycoconjugates on pathogen surfaces and has been found in complex with mannose-binding lectin-associated serine protease 1 (MASP-1) and/or MASP-3 in circulation. Mutation in the CL-11 gene was recently associated with the developmental syndrome 3MC. In the present study, we established and thoroughly validated a sandwich enzyme-linked immunosorbent assay (ELISA) based on two different monoclonal antibodies. The assay is highly sensitive, specific and shows excellent quantitative characteristics such as reproducibility, dilution linearity and recovery (97.7 104%). The working range is 0.15-34 ng/ml. The CL-11 concentration in two CL-11 deficient individuals affected by the 3MC syndrome was determined to be below 2.1 ng/ml. We measured the mean serum CL-11 concentration to 284 ng/ml in 100 Danish blood donors, with a 95% confidence interval of 269-299 ng/ml. There was no significant difference in the CL-11 concentration measured in matched serum and plasma samples. Storage of samples and repeated freezing and thawing to a certain extent did not influence the ELISA. This ELISA offers a convenient and reliable method for studying CL-11 levels in relation to a variety of human diseases and syndromes. PMID- 22301271 TI - The Lagerlunda collision and the introduction of color vision testing. AB - In histories of vision testing, the origins of occupational screening for color blindness are often traced to a fatal railroad accident that occurred in Sweden on the night of 14-15 November 1875. The scene of the accident was the estate of Baron Lagerfelt in Ostergotland, but the critical events were played out at Linkoping (the normal passing place for the northbound and southbound expresses) and at Bankeberg (a small station to which the passing place was reassigned at a few minutes' notice). First to arrive at Bankeberg, the northbound express slowed almost to a halt, but then inexplicably accelerated forwards towards the Lagerlunda estate, despite a sequence of signals from the stationmaster, Uno Bjorkelund, and a lineman, Oskar Johansson. Soon after the accident, the ophthalmologist Frithiof Holmgren suggested that the engineer of the northbound express, Andersson, or his oiler, Larsson, had been color blind. Neither survived to be tested. Using the records of the subsequent trial and other archival materials, we have re-examined the role of color blindness in the Lagerlunda incident and conclude that the accident cannot be attributed to color blindness alone. Yet the accident undoubtedly had a central role in the introduction of color vision testing by European and North American railroads. To persuade the railroad management to introduce universal screening of employees for color blindness, Holmgren used a dramatic coup de theatre and some unashamed subterfuge. PMID- 22301272 TI - Cytochrome P450 3A-mediated microsomal biotransformation of 1alpha,25 dihydroxyvitamin D3 in mouse and human liver: drug-related induction and inhibition of catabolism. AB - The biological activities of vitamin D(3) are exerted through the dihydroxy metabolite of vitamin D(3) [1alpha,25(OH)(2)D(3)]. Hepatic biotransformation of 1alpha,25(OH)(2)D(3) by cytochrome P450 (P450) enzymes could be an important determinant of bioavailability in serum and tissues. In the present study, we investigated the comparative biotransformation of 1alpha,25(OH)(2)D(3) in mouse and human liver microsomes and determined the effects of commonly used drugs on the catabolism of 1alpha,25(OH)(2)D(3). Severe symptoms of vitamin D deficiency have historically been observed in patients who received dexamethasone. To compare the effects of clinically important glucocorticoids with hepatic biotransformation of 1alpha,25(OH)(2)D(3), adult male CD-1 mice were given intraperitoneal injections of either vehicle (50% ethanol), dexamethasone (80 mg/kg per day), or prednisone (80 mg/kg per day) for three consecutive days. Hydroxy metabolite formation pattern and the extent of substrate depletion were similar in mouse liver microsomes (MLM) from vehicle- or prednisone-treated mice, whereas treatment with dexamethasone led to the emergence of additional metabolites and increased substrate depletion, as determined by liquid chromatography/mass spectrometry. The metabolite formation profile in vehicle treated mice was different from that of human liver microsomes (HLM). Selective P450 chemical inhibitors have demonstrated that CYP3A isoforms are responsible for the microsomal biotransformation of 1alpha,25(OH)(2)D(3) in MLM. Coincubation of 1alpha,25(OH)(2)D(3) with commonly used drugs led to approximately 60 to 100% inhibition of CYP3A4-mediated catabolism of 1alpha,25-(OH)(2)D(3) in HLM. A species-based difference was identified between CYP3A-mediated hepatic microsomal metabolism of 1alpha,25(OH)(2)D(3) in humans and mice. We have shown that the clinical importance of glucocorticoids differentially modulates catabolism of active vitamin D(3) and that commonly used drugs could affect vitamin D homeostasis. PMID- 22301273 TI - The ganglioside G(D2) induces the constitutive activation of c-Met in MDA-MB-231 breast cancer cells expressing the G(D3) synthase. AB - We have recently established and characterized cellular clones deriving from MDA MB-231 breast cancer cells that express the human G(D3) synthase (GD3S), the enzyme that controls the biosynthesis of b- and c-series gangliosides. The GD3S positive clones show a proliferative phenotype in the absence of serum or growth factors and an increased tumor growth in severe immunodeficient mice. This phenotype results from the constitutive activation of the receptor tyrosine kinase c-Met in spite of the absence of ligand and subsequent activation of mitogen-activated protein kinase/extracellular signal-regulated kinase and phosphoinositide 3-kinase/Akt pathways. Here, we show by mass spectrometry analysis of total glycosphingolipids that G(D3) and G(D2) are the main gangliosides expressed by the GD3S positive clones. Moreover, G(D2) colocalized with c-Met at the plasma membrane and small interfering RNA silencing of the G(M2)/G(D2) synthase efficiently reduced the expression of G(D2) as well as c-Met phosphorylation and reversed the proliferative phenotype. Competition assays using anti-G(D2) monoclonal antibodies also inhibit proliferation and c-Met phosphorylation of GD3S positive clones in serum-free conditions. Altogether, these results demonstrate the involvement of the disialoganglioside G(D2) in MDA MB-231 cell proliferation via the constitutive activation of c-Met. The accumulation of G(D2) in c-Met expressing cells could therefore reinforce the tumorigenicity and aggressiveness of breast cancer tumors. PMID- 22301274 TI - Emergent literacy in children with autism: an exploration of developmental and contextual dynamic processes. AB - PURPOSE: This investigation describes emergent literacy skills, print motivation, and home literacy environments in a linguistically diverse group of children with autism spectrum disorders (ASD). METHOD: Emergent literacy skills were directly assessed in 41 children between the ages of 4 and 8 years. Parent report was solicited to provide additional information concerning the children's emergent literacy skills, as well as their print motivation and home literacy environments. The achievements of children with differential language abilities were compared, and associations among the children's language and emergent literacy abilities were explored. RESULTS: Narrowly, children with typical language achieved significantly higher scores on an emergent literacy composite than those with mild-to-moderate or severe language impairments; broadly, these scores were highly correlated (rho = .56) with the children's language. Skill performance was varied but was characterized by relative strengths in discrete skills, such as letter name identification, and weaknesses in more holistic skills, such as print functions. Parents generally described the children as being motivated by print materials and the home environments as offering high levels of parent-child engagement in literacy activities. CONCLUSION: Profiles were associated with language and were illustrated by heterogeneity with potentially unequal achievements between code- and meaning-based skills. Implications for speech-language pathologists and other educators are provided. PMID- 22301275 TI - A polymerizable GFP variant. AB - Flagellin has the ability to polymerize into long filaments under appropriate conditions. Our work aims at the construction of flagellin-based fusion proteins which possess polymerization ability and preserve the functional properties of the fusion partner as well. The hypervariable D3 domain of Salmonella flagellin, containing residues 190-283, is a good target for genetic engineering studies since it can be extensively modified or removed without disturbing the self assembling ability. In this work a fusion construct of flagellin and the superfolder mutant of the green fluorescent protein were created by replacing D3 with superfolder green fluorescent protein (GFP). The obtained GFP variant was capable of forming stable, highly fluorescent filamentous assemblies. Our results imply that other proteins (enzymes, binding proteins, etc.) can also be furnished by polymerization ability in a similar way. This approach paves the way for the construction of multifunctional tubular nanostructures. PMID- 22301276 TI - The role of tryptophan in protein fibrillogenesis: relevance of Trp7 and Trp14 to the amyloidogenic properties of myoglobin. AB - In order to understand the role of tryptophan in the mechanisms of fibrils formation, the ability of a series of analogs of the residue 7-18 span of myoglobin to form amyloid-like fibrils was investigated. Alternatively one or both tryptophans were substituted with alanine and leucine, to determine the contribution of hydrophobicity and aromaticity. The scale of aggregation propensity of the peptides determined indicates that tryptophan is crucial for the amyloidogenic process. Since the rare tryptophan residue is generally engaged in structural roles in proteins, or when exposed serves as binding sites, we surmise that its exposure in the amyloidogenic fragments allows for intermolecular clustering with residues from other molecules leading to the formation of amyloid aggregates. PMID- 22301277 TI - Does somatic illness explain the association between common mental disorder and elevated mortality? Findings from extended follow-up of study members in the UK Health and Lifestyle Survey. AB - BACKGROUND: Common mental disorder (psychological distress) is associated with an increased risk of disease-specific mortality. Given that physical illness is related to both exposure and outcome, it may explain this relation through confounding or mediation. METHODS: The authors used a 20-year follow-up of the UK Health and Lifestyle Survey (6127 men and women) in which common mental disorder was ascertained at baseline using the 30 item General Health Questionnaire and physical illness using a range of enquiries. Study members were an average of 45.2 years (SD 17.0) at study induction. RESULTS: In age-adjusted analyses, a 1 SD increase in common mental disorder score was associated with an elevated risk of mortality outcomes coronary heart disease (CHD) in men (HR 1.11, 95% CI 0.96 to 1.27), CHD in women (1.33, 1.16 to 1.51); plus, in men and women combined, stroke (1.13, 0.96 to 1.30), respiratory disease (1.31, 1.15 to 1.48), lung cancer (1.11, 0.92 to 1.33), 'other' cancer (1.14, 1.03 to 1.26) and all causes (1.18, 1.12 to 1.23). Controlling for prior physical illness effectively eliminated the common mental disorder-mortality relation in all analyses with the exception of CHD in women. CONCLUSION: That physical illness largely explains the link between common mental disorder and mortality in the present cohort is compatible with either a confounding or mediation explanation. PMID- 22301278 TI - Diabetes and raised blood glucose as risk factors for future suicide: cohort study of 1 234 927 Korean men and women. AB - BACKGROUND: A diagnosis of diabetes has been shown to be a risk factor for suicide in selected studies. The link between blood glucose and future suicide has yet to be examined. AIM: To examine if diabetes and blood glucose level are associated with a raised risk of suicide. Methods The Korean Cancer Prevention Study is a cohort of 1,329,525 individuals (482,618 women) aged 30-95 years at baseline. A fasting serum specimen was assayed for blood glucose, and diabetes status was categorised into five groups based on existing definitions. Study members were followed for mortality experience over 14 years. RESULTS: There were 472 suicide deaths (389 in men and 83 in women) during the follow-up. In men, there was a 'J'-shaped diabetes-suicide death relation. Thus, while the highest suicide rates were apparent in those with type 2 diabetes and there was an incremental fall in suicide risk with decreasing blood glucose level, an inflection was seen in the low-normal group. Similar results were apparent in women, although there was no raised risk in the lowest blood glucose group. CONCLUSION: In the present cohort, diabetes (both existing and study detected) but not raised blood glucose was a risk factor for completed suicide. PMID- 22301279 TI - Lamin A/C protein is overexpressed in tissue-invading prostate cancer and promotes prostate cancer cell growth, migration and invasion through the PI3K/AKT/PTEN pathway. AB - Prostate cancer (PC) remains the second most common cause of cancer-related death in Western countries. A previous proteomics study suggested that the nuclear membrane protein lamin A/C to be a maker to discriminate low- and high-Gleason score tumors and to identify high-risk cancers. To characterize its function in PC cells, we performed a detailed expression analysis in PC tissue and explored the consequences of down or upregulation of lamin A/C in PC cells. Our results confirm an increased lamin A/C protein expression in high-risk cancers and show association of expression with tumor cell formations at the invasion fronts of tumors and in invasion 'spearheading' tumor cell clusters. In the prostate tumor cell lines, LNCaP, DU145, and PC3 small hairpin RNA knockdown or overexpression of lamin A/C resulted in inhibition or stimulation, respectively, of cell growth, colony formation, migration and invasion. Further mechanism studies suggested that the lamin A/C-related malignant behavior is regulated through modulation of the phosphoinositide 3-kinase (PI3K)/AKT/PTEN signaling pathway. Western blot results indicated that knockdown or overexpression of lamin A/C decreased or increased, respectively, protein levels of the PI3K subunits p110 and p85 in all three cell lines; phosphor-AKT in the PTEN-negative cell lines LNCaP and PC3, and, increased or decreased, respectively, PTEN protein levels in PTEN-positive DU145 cells. Together, our data suggest that lamin A/C proteins are positively involved in malignant behavior of PC cells through the PI3K/AKT/PTEN pathway. Lamin A/C may represent a new oncogenic factor and a novel therapeutic target for PC. PMID- 22301280 TI - Small molecules that bind the Mdm2 RING stabilize and activate p53. AB - p53 is a tumor suppressor that responds to a variety of stresses such as oncogenes and DNA damage by activating its transcriptional targets to allow repair or elimination of damaged cells. In the absence of stress signals, p53 needs to be kept in check and this is achieved by the E3 ligase MDM2. For tumors that retain wild-type p53, therapeutic strategies aimed at removing the inhibitory activity of MDM2 on p53 are under development and to date have focused on drugs that prevent the binding of p53 to MDM2. Here, we report the analysis of a group of synthetic analogs derived from 5-deazaflavin compounds previously identified in a screen as inhibitors of MDM2 autoubiquitination. Using measurement of surface plasmon resonance, we demonstrated that active 5 deazaflavin analogs bind to the MDM2 RING, whereas inactive compounds show no binding. In cellular assays, these active MDM2 RING binding compounds inhibited the ubiquitination of p53, stabilized p53, led to increased expression of p53 targets and caused corresponding cell cycle effects. Deazaflavin analogs therefore function to activate p53 through a novel mechanism, by inhibiting the E3 ligase activity of MDM2 in a manner that involves binding to the MDM2 RING. PMID- 22301281 TI - Genetic variants in carcinogen-metabolizing enzymes, cigarette smoking and pancreatic cancer risk. AB - Individual susceptibility to the toxic effects of cigarette smoke may be modified by inherited variability in carcinogen metabolism. The purpose of the present study was to investigate pancreatic cancer risk associated with cigarette smoking and 33 variants within carcinogen metabolism genes and examine whether these variants modify the association between smoking and pancreatic cancer. A population-based study was conducted with 455 pancreatic cancer cases and 893 controls. Epidemiological and smoking data were collected from questionnaires and variants were genotyped by mass spectrometry. Age- and sex-adjusted odds ratio (ASOR) and multivariate-adjusted odds ratio (MVOR) estimates were obtained using multivariate logistic regression, and interactions between each variant and smoking were investigated. Current smoker status [MVOR = 2.29, 95% confidence interval (95% CI): 1.62, 3.22], 10-27 pack-years (MVOR = 1.57, 95% CI: 1.13, 2.18), >27 pack-years (MVOR = 1.77, 95% CI: 1.27, 2.46) and longer durations of smoking (19-32 years: MVOR = 1.46, 95% CI: 1.05, 2.05; >32 years: MVOR = 1.78, 95% CI: 1.30, 2.45) were associated with increased pancreatic cancer risk. CYP1B1 4390-GG (ASOR = 0.36, 95% CI: 0.15, 0.86) and Uridine 5'-diphospho glucuronosyltransferase 1 family, polypeptide A7-622-CT (ASOR = 0.77, 95% CI: 0.60, 0.99) were associated with reduced risk. N-acetyltransferase 1-640-GT/GG (ASOR = 1.75, 95% CI: 1.00, 3.05), GSTM1 (rs737497)-GG (ASOR = 1.41, 95% CI: 1.02, 1.95), GSTM1 gene deletion (ASOR = 4.89, 95% CI: 3.52, 6.79) and glutathione S-transferase theta-1 gene deletion (ASOR = 4.41, 95% CI: 2.67, 7.29) were associated with increased risk. Significant interactions were observed between pack-years and EPHX1-415 (P = 0.04) and smoking status and N acetyltransferase 2-857 (P = 0.03). Variants of carcinogen metabolism genes are independently associated with pancreatic cancer risk and may modify the risk posed by smoking. PMID- 22301283 TI - The global knowledge society. PMID- 22301282 TI - Id-1 and the p65 subunit of NF-kappaB promote migration of nasopharyngeal carcinoma cells and are correlated with poor prognosis. AB - Inhibitor of differentiation (Id)-1 and nuclear factor-kappa B (NF-kappaB) have been detected in many malignant tumors, and their presence has been correlated with the metastatic potential of these tumors. This study was undertaken to investigate the prognostic significance of the expression of Id-1 and the p65 subunit of NF-kappaB (NF-kappaB/p65) and the proteins' roles in the invasion process of nasopharyngeal carcinoma (NPC) cells. The messenger RNA (mRNA) and protein levels of Id-1 and NF-kappaB/p65 in normal nasopharyngeal epithelial cells and NPC cell lines were examined using reverse transcription-PCR and western blot analysis, whereas the mRNA and protein levels of Id-1 and NF kappaB/p65 in clinical NPC specimens were determined by reverse transcription-PCR and immunohistochemistry. Short hairpin RNA (shRNA) was used to silence Id-1 and NF-kappaB/p65 to allow for the examination of matrix metalloproteinase (MMP)-9 expression and migratory capacity changes in CNE-2 cells. Multivariate Cox analysis revealed that elevated Id-1 expression was a significant independent predictor of the 5 year overall survival rate (hazards ratio = 16.720, P = 0.005). Furthermore, elevated expression of both Id-1 and NF-kappaB/p65 was associated with poor clinical survival (P = 0.049). Targeting Id-1 and NF kappaB/p65 mRNA with shRNA in CNE-2 cells inhibited MMP-9 expression and decreased the migratory capacity of CNE-2 cells. In conclusion, Id-1 expression is a novel independent prognostic marker molecule that helps identify NPC patients with a poor prognosis. Additionally, combined analysis of Id-1 and NF kappaB/p65 can be useful for identifying patients at risk for unfavorable clinical outcomes. Id-1 or/and NF-kappaB/p65 enhanced tumor cell migration, which is associated with the secretion of MMP-9. PMID- 22301288 TI - Avian influenza. The limits of avian flu studies in ferrets. PMID- 22301289 TI - Cell biology. Donation spurs a cell observatory--and bigger plans. PMID- 22301290 TI - Astronomy. Celebrated exoplanet vanishes in a cloud of dust--or maybe not. PMID- 22301291 TI - Genomics. China's sequencing powerhouse comes of age. PMID- 22301292 TI - Ecology. Rebuilding wetlands by managing the muddy Mississippi. PMID- 22301293 TI - Oil resources. Technology is turning U.S. oil around but not the world's. PMID- 22301294 TI - 2011 International Science & Engineering Visualization Challenge. PMID- 22301300 TI - Investing in Libya's education. PMID- 22301301 TI - Invasive species unchecked by climate. PMID- 22301304 TI - Comment on "Abiotic pyrite formation produces a large Fe isotope fractionation". AB - Guilbaud et al. (Reports, 24 June 2011, p. 1548) suggest that the geologic record of Fe isotope fractionation can be explained by abiological precipitation of pyrite. We argue that a detailed understanding of the depositional setting, mineralogy, and geologic history of Precambrian sedimentary rocks indicates that the Fe isotope record dominantly reflects biological fractionations and Fe redox processes. PMID- 22301306 TI - Proceed with planning despite multiple models. PMID- 22301307 TI - Scientific publications. Coercive citation in academic publishing. PMID- 22301308 TI - Economics. Ready, steady, compete. PMID- 22301309 TI - Evolution. Surviving in a toxic world. PMID- 22301310 TI - Neuroscience. To stop or not to stop? PMID- 22301311 TI - Climate change. Marching in near lock-step. PMID- 22301312 TI - Physics. Seeing the superfluid transition of a gas. PMID- 22301313 TI - Nanoscopy in a living mouse brain. AB - We demonstrated superresolution optical microscopy in a living higher animal. Stimulated emission depletion (STED) fluorescence nanoscopy reveals neurons in the cerebral cortex of a mouse with <70-nanometer resolution. Dendritic spines and their subtle changes can be observed at their relevant scales over extended periods of time. PMID- 22301314 TI - Spin-down of radio millisecond pulsars at genesis. AB - Millisecond pulsars are old neutron stars that have been spun up to high rotational frequencies via accretion of mass from a binary companion star. An important issue for understanding the physics of the early spin evolution of millisecond pulsars is the impact of the expanding magnetosphere during the terminal stages of the mass-transfer process. Here, I report binary stellar evolution calculations that show that the braking torque acting on a neutron star, when the companion star decouples from its Roche lobe, is able to dissipate >50% of the rotational energy of the pulsar. This effect may explain the apparent difference in observed spin distributions between x-ray and radio millisecond pulsars and help account for the noticeable age discrepancy with their young white dwarf companions. PMID- 22301315 TI - Iron catalysts for selective anti-Markovnikov alkene hydrosilylation using tertiary silanes. AB - Alkene hydrosilylation, the addition of a silicon hydride (Si-H) across a carbon carbon double bond, is one of the largest-scale industrial applications of homogeneous catalysis and is used in the commercial production of numerous consumer goods. For decades, precious metals, principally compounds of platinum and rhodium, have been used as catalysts for this reaction class. Despite their widespread application, limitations such as high and volatile catalyst costs and competing side reactions have persisted. Here, we report that well-characterized molecular iron coordination compounds promote the selective anti-Markovnikov addition of sterically hindered, tertiary silanes to alkenes under mild conditions. These Earth-abundant base-metal catalysts, coordinated by optimized bis(imino)pyridine ligands, show promise for industrial application. PMID- 22301316 TI - Natural variation in a chloride channel subunit confers avermectin resistance in C. elegans. AB - Resistance of nematodes to anthelmintics such as avermectins has emerged as a major global health and agricultural problem, but genes conferring natural resistance to avermectins are unknown. We show that a naturally occurring four amino-acid deletion in the ligand-binding domain of GLC-1, the alpha-subunit of a glutamate-gated chloride channel, confers resistance to avermectins in the model nematode Caenorhabditis elegans. We also find that the same variant confers resistance to the avermectin-producing bacterium Streptomyces avermitilis. Population-genetic analyses identified two highly divergent haplotypes at the glc 1 locus that have been maintained at intermediate frequencies by long-term balancing selection. These results implicate variation in glutamate-gated chloride channels in avermectin resistance and provide a mechanism by which such resistance can be maintained. PMID- 22301317 TI - Affirmative action policies promote women and do not harm efficiency in the laboratory. AB - Gender differences in choosing to enter competitions are one source of unequal labor market outcomes concerning wages and promotions. Given that studying the effects of policy interventions to support women is difficult with field data because of measurement problems and potential lack of control, we evaluated, in a set of controlled laboratory experiments, four interventions: quotas, where one of two winners of a competition must be female; two variants of preferential treatment, where a fixed increment is added to women's performance; and repetition of the competition, where a second competition takes place if no woman is among the winners. Compared with no intervention, all interventions encourage women to enter competitions more often, and performance is at least equally good, both during and after the competition. PMID- 22301318 TI - Untangling genomes from metagenomes: revealing an uncultured class of marine Euryarchaeota. AB - Ecosystems are shaped by complex communities of mostly unculturable microbes. Metagenomes provide a fragmented view of such communities, but the ecosystem functions of major groups of organisms remain mysterious. To better characterize members of these communities, we developed methods to reconstruct genomes directly from mate-paired short-read metagenomes. We closed a genome representing the as-yet uncultured marine group II Euryarchaeota, assembled de novo from 1.7% of a metagenome sequenced from surface seawater. The genome describes a motile, photo-heterotrophic cell focused on degradation of protein and lipids and clarifies the origin of proteorhodopsin. It also demonstrates that high-coverage mate-paired sequence can overcome assembly difficulties caused by interstrain variation in complex microbial communities, enabling inference of ecosystem functions for uncultured members. PMID- 22301319 TI - Sequential signaling crosstalk regulates endomesoderm segregation in sea urchin embryos. AB - The segregation of embryonic endomesoderm into separate endoderm and mesoderm fates is not well understood in deuterostomes. Using sea urchin embryos, we showed that Notch signaling initiates segregation of the endomesoderm precursor field by inhibiting expression of a key endoderm transcription factor in presumptive mesoderm. The regulatory circuit activated by this transcription factor subsequently maintains transcription of a canonical Wnt (cWnt) ligand only in endoderm precursors. This cWnt ligand reinforces the endoderm state, amplifying the distinction between emerging endoderm and mesoderm. Before gastrulation, Notch-dependent nuclear export of an essential beta-catenin transcriptional coactivator from mesoderm renders it refractory to cWnt signals, insulating it against an endoderm fate. Thus, we report that endomesoderm segregation is a progressive process, requiring a succession of regulatory interactions between cWnt and Notch signaling. PMID- 22301320 TI - Growth of Western Australian corals in the anthropocene. AB - Anthropogenic increases of atmospheric carbon dioxide lead to warmer sea surface temperatures and altered ocean chemistry. Experimental evidence suggests that coral calcification decreases as aragonite saturation drops but increases as temperatures rise toward thresholds optimal for coral growth. In situ studies have documented alarming recent declines in calcification rates on several tropical coral reef ecosystems. We show there is no widespread pattern of consistent decline in calcification rates of massive Porites during the 20th century on reefs spanning an 11 degrees latitudinal range in the southeast Indian Ocean off Western Australia. Increasing calcification rates on the high latitude reefs contrast with the downward trajectory reported for corals on Australia's Great Barrier Reef and provide additional evidence that recent changes in coral calcification are responses to temperature rather than ocean acidification. PMID- 22301321 TI - Abnormal brain structure implicated in stimulant drug addiction. AB - Addiction to drugs is a major contemporary public health issue, characterized by maladaptive behavior to obtain and consume an increasing amount of drugs at the expense of the individual's health and social and personal life. We discovered abnormalities in fronto-striatal brain systems implicated in self-control in both stimulant-dependent individuals and their biological siblings who have no history of chronic drug abuse; these findings support the idea of an underlying neurocognitive endophenotype for stimulant drug addiction. PMID- 22301322 TI - Safety surrounding parenteral nutrition systems. AB - Parenteral nutrition (PN) is one of the most complex medications administered to hospitalized and ambulatory patients. Despite the successful clinical use of PN for over 3 decades, adverse events continue to occur, resulting in serious morbidity or even mortality. There are multiple points within the PN process for errors to occur: prescribing, transcription, preparation, and administration. Because of the lack of published literature about PN errors, a formal study was conducted to document the nature and severity of harm resulting from medication errors during the PN process. PMID- 22301323 TI - Parenteral nutrition therapy over the next 5-10 years: where are we heading? AB - Parenteral nutrition (PN) is one of the most complex medical therapies prescribed by healthcare professionals because it is dependent on the compounding of multiple base solutions to arrive at the final formulation. The delivery of PN is associated with errors in ordering, transcribing, compounding, and delivery of the PN formulations. New compounding technologies will attempt to minimize the potential for these errors. In addition, the associated infectious complications associated with PN therapy need to be minimized. Commercially prepared, premixed, terminally sterilized PN solutions may have an impact. Broader decontamination technologies will be implemented to reduce the incidence of overall nosocomial infections. Modification of PN nutrients, particularly intravenous fat emulsions, will be provided by alternative biological sources, creating fats that may have an improved impact on the patient's immune system and ultimately affecting clinical outcomes. PMID- 22301324 TI - Compounding vs standardized commercial parenteral nutrition product: pros and cons. AB - Standardized commercial parenteral nutrition (PN) formulations have advantages and disadvantages as compared with PN formulations compounded using an automated compounding device. These advantages and disadvantages are discussed along with the supporting available research. PMID- 22301325 TI - Parenteral nutrition prescribing processes using computerized prescriber order entry: opportunities to improve safety. AB - The prescribing and processing of parenteral nutrition (PN) orders for pediatric patients may involve multiple steps, be time-consuming, and have opportunity for error if safety measures are not in place. The process can vary from institution to institution. The authors conducted a comparison of their system for the prescribing and processing of PN orders with the American Society for Parenteral and Enteral Nutrition's (A.S.P.E.N.'s) Safe Practices for Parenteral Nutrition guidelines. Using a computerized prescriber order entry (CPOE) system allowed for compliance with most of the elements. The safety data demonstrated an overall low rate of transcription errors, an inherent risk when the CPOE system does not communicate directly with the automated compounding device (ACD). There was a 5% overall pharmacist intervention rate on PNs, similar to the 6%-8% rate seen with other medications. Approximately 6% of these PN interventions had an outcome associated with preventing an adverse drug reaction, toxicity, or medication error. Implementation of additional safety measures and standardization may have a positive impact on the complicated process of prescribing and processing PN orders at the authors' institution. PMID- 22301326 TI - Introduction and goals of the A.S.P.E.N. parenteral nutrition safety summit. PMID- 22301327 TI - Drug shortages and training. PMID- 22301328 TI - Safety: Not just a "buzzword" but an "action word" for A.S.P.E.N. PMID- 22301329 TI - Oxidative stress. AB - Oxidative stress is defined by an imbalance between increased levels of reactive oxygen species (ROS) and a low activity of antioxidant mechanisms. An increased oxidative stress can induce damage to the cellular structure and potentially destroy tissues. However, ROS are needed for adequate cell function, including the production of energy by the mitochondria. Increased oxidative stress has been incriminated in physiological conditions, such as aging and exercise, and in several pathological conditions, including cancer, neurodegenerative diseases, cardiovascular diseases, diabetes, inflammatory diseases, and intoxications. However, prevention by antioxidants has been mostly inefficient. Therefore, a rigorous scientific evaluation in well-defined conditions is mandatory to define the appropriate place for manipulations of the oxidative pathways in human medicine. PMID- 22301330 TI - Fatty emaciation: a case report of suspected fat overload syndrome in oral refeeding. AB - Refeeding syndrome has been observed in patients receiving nutrition after a prolonged period of malnourishment and is characterized by multiple metabolic derangements. Besides hypophosphatemia and hypoglycemia, lipemia has been described in association with parenteral nutrition administration to the malnourished. The authors describe one anorexic patient who developed lipemia during oral refeeding, followed by a precipitous drop in hematocrit suggestive of fat overload syndrome. PMID- 22301331 TI - The Canadian Home Total Parenteral Nutrition (HTPN) Registry: vitamin K supplementation and bone mineral density. AB - BACKGROUND: Vitamin K supplementation improves bone health, and its absence might be associated with low bone mineral density (BMD). The authors aim to assess vitamin K supplementation practices in Canadian home parenteral nutrition (HPN) programs and their relationship with BMD. METHODS: This is a cross-sectional study of 189 patients from the Canadian HPN registry. RESULTS: All 189 patients studied received M.V.I.-12, which does not contain vitamin K. Of those, 41.3% were supplemented with 10 mg of intravenous vitamin K (VK+) weekly, whereas the others did not receive vitamin K except via lipid emulsion (VK-). Short bowel syndrome accounted for 69% of VK+ and 46% of VK- patients. On univariate analysis, VK+ patients had substantially lower body mass index (BMI) and received lower bisphosphonate infusion than did VK-patients. There were no statistically significant differences in HPN calcium or lipid content, liver function test results, age, sex, or reason for HPN between the 2 groups. Patients who were VK+ had higher lumbar spine T scores and hip T scores than did VK-patients. General linear modeling analysis, adjusted for BMI, age, PN magnesium, PN phosphate, PN calcium, and bisphosphonate as possible predictors of BMD, showed a trend toward better hip T scores (P = .063) for VK+ patients compared with VK- patients. CONCLUSION: In HPN patients supplemented with vitamin K, the trend toward a better hip BMD compared with no supplementation suggests a role for vitamin K in preserving BMD. This requires further study. PMID- 22301332 TI - Consensus of parenteral nutrition safety issues and recommendations. PMID- 22301333 TI - No pain no gain? Pursuing a competing goal inhibits avoidance behavior. AB - This experiment investigated pain-related avoidance behavior in context of competing goals. Participants (N=56) were presented trials of 2 different tasks of which 1 task could produce pain. They were free to decide whether or not to perform trials of these tasks. In half of the participants, a competing goal was activated by instructing them that they would receive a monetary reward corresponding to the number of pain task trials actually performed (competition group). In the other half of the participants, no competing goal was installed (control group). Results showed that the competition group showed less frequent avoidance behavior than the control group. Furthermore, the association between pain-related avoidance behavior and fear of pain was smaller in the competition group than in the control group. The findings indicate that the emergence of pain related avoidance behavior depends upon the motivational context, and that the association between pain-related fear and avoidance is not stable. This study has implications for our understanding of disability, and points to the need to consider avoidance behavior within a broad context of multiple, often competing, goals. PMID- 22301334 TI - Synthesis and characterization of betaine-like diacyl lipids: zwitterionic lipids with the cationic amine at the bilayer interface. AB - We synthesized and characterized a series of zwitterionic, acetate-terminated, quaternized amine diacyl lipids (AQ). These lipids have an inverted headgroup orientation as compared to naturally occurring phosphatidylcholine (PC) lipids; the cationic group is anchored at the membrane interface, while the anionic group extends into the aqueous phase. AQ lipids preferentially interact with highly polarizable anions (ClO(4)(-)) over less polarizable ions (Cl(-)), in accord with the Hofmeister series, as measured by the change in zeta potential of AQ liposomes. Conversely, AQ lipids have a weaker association with calcium than do PC lipids. The transition temperatures (Tm) of the AQ lipids are similar to the Tm observed with phosphatidylethanolamine (PE) lipids of the same chain length. AQ lipids form large lipid sheets after heating and sonication; however, in the presence of cholesterol (Chol), these lipids form stable liposomes that encapsulate carboxyfluorescein. The AQ:Chol liposomes retain their contents in the presence of serum at 37 degrees C, and when injected intravenously into mice, their organ biodistribution is similar to that observed with PC:Chol liposomes. AQ lipids demonstrate that modulating the headgroup charge orientation significantly alters the biophysical properties of liposomes. For the drug carrier field, these new materials provide a non-phosphate containing zwitterlipid for the production of lipid vesicles. PMID- 22301335 TI - Endovascular treatment of descending thoracic aortic disease: single-center, 15 year experience. AB - PURPOSE: To report the experience with thoracic endovascular aortic repair (TEVAR) in a single center over a 15-year period. MATERIALS AND METHODS: All patients undergoing TEVAR during the period 1994-2009 were retrospectively evaluated. RESULTS: The study comprised 133 patients (96 men, age 69.5 years +/- 14.7) who underwent 21 emergency and 112 elective TEVAR procedures. Aortic pathologies included 91 aneurysms, 14 pseudoaneurysms, 14 penetrating ulcers with or without pseudoaneurysms or intramural hematomas, 8 type B dissections (3 acute and 5 chronic), and 6 traumatic transections. Technical success was 97.7% with a 30-day mortality of 7.5%. There were 101 patients followed to 1 year, 35 patients followed to 5 years, and 6 patients followed to 10-15 years. The overall estimated survivals at 1 year, 5 years, and 10 years were 81%, 48%, and 36%. The 30-day mortality rates in emergency and elective TEVAR procedures were 23.9% and 4.5% (P = .005). However, among patients who survived > 30 days, there was no significant difference in mortality between groups undergoing emergency and elective TEVAR procedures (P = .9, hazard ratio [HR] 0.94, confidence interval [CI] 0.4-2.2). There was no significant gender survival difference. The 30-day mortality rate in octogenarians (n = 31) was higher than in younger patients (P = .03). Incidences of stroke and paraplegia within 30 days of TEVAR were 6.8% and 2.2%. Endoleaks were found in 39 (29%) patients, and secondary interventions were performed in 6 (4.5%) patients. CONCLUSIONS: The data support the safety and efficacy of TEVAR for aortic pathologies with a low mortality rate. Younger patients have fewer complications after TEVAR. After the acute perioperative period, TEVAR procedures performed emergently are as durable as the procedures performed electively. PMID- 22301336 TI - [Editorial]. PMID- 22301337 TI - Determination of the orientational order parameter of the homologous series of 4 cyanophenyl 4-alkylbenzoate (n.CN) by different methods. AB - The orientational order parameters of a homologous series of 4-cyanophenyl 4 alkylbenzoates have been determined at different temperatures from (13)C-NMR, x ray diffraction, optical birefringence, high resolution density and diamagnetic susceptibility anisotropy measurements. To determine the temperature dependence of the orientational order parameter from the (13)C chemical shift values, the two-dimensional polarization inversion spin exchange at the magic angle (PISEMA) method was also used for the measurement of (13)C-(1)H dipolar couplings at different sites in the oriented phase. The nematic order parameters determined from each of these methods have been compared. Apart from a slight shift in their values their trends with temperature are very similar. The differences among the results obtained by these five different methods have been discussed. From the high resolution density data, the values of the critical exponents near the T(N I) transition are found to lie between the Ising model and tricritical behaviour. PMID- 22301338 TI - New 10F soft and pliable polyurethane stents decrease the migration rate compared with conventional 10F polyethylene stents in hilar biliary obstruction: results of a pilot study. AB - BACKGROUND: Migration of biliary stents is a well-documented problem that can result in a variety of complications. The newly designed polyurethane (PU) stent, which is made of a soft and pliable material, may prevent distal and proximal stent migration. OBJECTIVE: To compare the migration rate of the PU stent with that of the conventional polyethylene stent (PE). DESIGN: Prospective, comparative, randomized trial. SETTING: Tertiary academic medical centers. PATIENTS: Fifty patients with a hilar stricture who had not undergone a previous drainage procedure. INTERVENTION: In patients with hilar stricture, random assignment of either a PU stent or PE stent. MAIN OUTCOME MEASUREMENT: The rate of early proximal or distal migration before stent occlusion. RESULTS: Overall and distal migration rates were significantly lower in the PU group than in the PE group (4.5% vs 29%, P = .032 and 4.5% vs 26.1%, P = .049, respectively). There was no significant difference between the migration rate in benign and malignant biliary strictures (5.9% vs 21.4%, P = .167). Sex, stent length, preprocedure bilirubin level, and Bismuth type were not associated with migration rate in either the PU or PE group. Median stent patency was 148 days (range 36-224 days) in the PU group and 151 days (range 40-241 days) in the PE group (P = .891). LIMITATIONS: Small sample size. CONCLUSIONS: Use of the new PU stent, which is soft and pliable, decreased distal migration. The PU stent patency rates appear similar, but this study is not powered to demonstrate equivalency of patency. PMID- 22301339 TI - Diagnostic yield of colonoscopy to evaluate melena after a nondiagnostic EGD. AB - BACKGROUND: Melena can be caused by bleeding from lower GI sources. Colonoscopy is frequently used to investigate melena after a nondiagnostic EGD. OBJECTIVE: To determine the diagnostic yield and rate of therapeutic intervention during colonoscopy in patients with melena and a nondiagnostic EGD. DESIGN: Retrospective case-control study. SETTING: Community and academic centers over a diverse geographic area in the United States. PATIENTS: This study involved patients in the Clinical Outcomes Research Initiative database with a colonoscopy performed to investigate melena within 30 days of a nondiagnostic EGD for the same indication. A control group had colonoscopies performed for average-risk screening. MAIN OUTCOME MEASUREMENTS: The endoscopic finding of a suspected bleeding source defined as right-sided arteriovenous malformation, colitis, polyp >= 20 mm, tumor, or ulcer. Rate of therapeutic intervention during colonoscopy. RESULTS: Colonoscopy found a suspected bleeding source in 4.8% of patients with melena, more frequently than in the control group (odds ratio [OR] 2.17; 95% confidence interval [CI], 1.65-2.86; P < .0001). The rate of therapeutic intervention during melena-related colonoscopy was 1.7%. Patients with melena were more likely to have a colon tumor (OR 2.87; 95% CI, 1.82-5.51; P < .0001) than were control patients. LIMITATIONS: Retrospective design, conclusions being dependent on the accuracy of database input, and lack of pertinent clinical data (eg, hemoglobin). CONCLUSION: The diagnostic yield of colonoscopy to investigate melena after nondiagnostic EGD is low. The need for therapeutic intervention during colonoscopy for this indication is very low. This population should undergo colonoscopy because they are at increased risk of colorectal cancer. Colonoscopy can potentially be performed electively in stable patients without continued bleeding. PMID- 22301340 TI - Laparoscopy-assisted versus balloon enteroscopy-assisted ERCP in bariatric post Roux-en-Y gastric bypass patients. AB - BACKGROUND: Data on balloon enteroscopy-assisted ERCP (BEA-ERCP) versus laparoscopy-assisted ERCP (LA-ERCP) in post-Roux-en-Y gastric bypass (RYGB) patients are lacking. OBJECTIVES: To compare BEA-ERCP with LA-ERCP in post-RYGB patients and to identify factors that predict therapeutic success with BEA-ERCP. DESIGN: Retrospective chart review. SETTING: A single North American tertiary referral center. PATIENTS: The review included 56 bariatric post-RYGB patients who underwent ERCP. INTERVENTIONS: BEA-ERCP or LA-ERCP. MAIN OUTCOME MEASUREMENTS: Cannulation rate, therapeutic success, hospital stay, complications, procedure duration, endoscopist time, and cost. RESULTS: A total of 32 patients underwent BEA-ERCP, and 24 underwent LA-ERCP. LA-ERCP was superior to BEA-ERCP in papilla identification (100% vs 72%, P = .005), cannulation rate (100% vs 59%, P < .001), and therapeutic success (100% vs 59%, P < .001). The total procedure time was shorter (P < .001) and endoscopist time was longer (P = .006) for BEA-ERCP. There was no difference in postprocedure hospital stay (P = .127) or complication rate (P = .392) between the 2 groups. In the BEA-ERCP group, in patients having a Roux limb + biliopancreatic (from ligament of Treitz to jejunojejunal anastomosis), a limb length less than 150 cm was associated with therapeutic success. Starting with BEA-ERCP and continuing with LA-ERCP after a failed BEA-ERCP saved $1015 compared with starting with LA-ERCP. LIMITATIONS: Single center, retrospective study. CONCLUSIONS: In centers with expertise in deep enteroscopy and ERCP, post-RYGB patients with a Roux + ligament of Treitz to jejunojejunal anastomosis limb length less than 150 cm should first be offered deep enteroscopy-assisted ERCP. In patients with Roux + ligament of Treitz to jejunojejunal anastomosis (LTJJ) limb length 150 cm or longer, LA-ERCP should be the preferred approach because of the lack of need for a second procedure, equivalent morbidity and hospital stay, decreased endoscopist time, and decreased cost. PMID- 22301341 TI - Endoscopic submucosal dissection for pig esophagus by using photocrosslinkable chitosan hydrogel as submucosal fluid cushion. AB - BACKGROUND: Hypertonic saline solution (HS) as a submucosal fluid cushion (SFC) for endoscopic submucosal dissection (ESD) has several disadvantages, including a short effect duration and increased risk of bleeding and perforation. Photocrosslinkable chitosan hydrogel in DMEM/F12 medium (PCH) can be converted into an insoluble hydrogel by UV irradiation for 30 seconds. OBJECTIVE: To evaluate the feasibility, usefulness, and safety of PCH as an SFC for ESD of esophagi, compared with HS and sodium hyaluronate (SH). DESIGN: Survival animal study. SETTINGS: Research laboratory study of 24 pig models in vivo. INTERVENTIONS: Twenty-four pigs were used in the 2 steps: First, ESD of the esophagus was performed with PCH, SH, or HS (each n = 6) as an SFC, and the effects of these agents on wound healing were examined endoscopically and histologically. Second, in vivo degradation of PCH (n = 3) and HS (n = 3) was examined in independent pig esophagi. MAIN OUTCOME MEASUREMENTS: Outcome measurements included feasibility and safety of PCH-assisted ESD of esophagus, gross and histologic evidence of the treated esophagus, biodegradation of injected PCH, and clinical tolerance by the animals. RESULT: PCH injection led to a longer-lasting elevation with clearer margins compared with SH and HS, thus enabling precise ESD along the margins of the elevated mucosa without complications such as bleeding and perforation. The aspects of wound repair after PCH-assisted ESD were similar to those of SH- and HS-assisted ESDs. Biodegradation of PCH was confirmed to be almost completed within 8 weeks on the basis of endoscopic and histologic observations. LIMITATIONS: In vivo animal model study. CONCLUSION: PCH permits more reliable ESD of the esophagus without complications than do SH and HS. Furthermore, the applied PCH appeared to be completely biodegraded within 8 weeks. Thus, PCH is a promising agent as an SFC in ESD of the esophagus. PMID- 22301342 TI - First report of endoscopic closure of a gastrocolic fistula using an over-the scope clip system (with video). PMID- 22301343 TI - Vital-dye enhanced fluorescence imaging of GI mucosa: metaplasia, neoplasia, inflammation. AB - BACKGROUND: Confocal endomicroscopy has revolutionized endoscopy by offering subcellular images of the GI epithelium; however, the field of view is limited. Multiscale endoscopy platforms that use widefield imaging are needed to better direct the placement of high-resolution probes. DESIGN: Feasibility study. OBJECTIVE: This study evaluated the feasibility of a single agent, proflavine hemisulfate, as a contrast medium during both widefield and high-resolution imaging to characterize the morphologic changes associated with a variety of GI conditions. SETTING: The University of Texas MD Anderson Cancer Center, Houston, Texas, and Mount Sinai Medical Center, New York, New York. PATIENTS, INTERVENTIONS, AND MAIN OUTCOME MEASUREMENTS: Resected specimens were obtained from 15 patients undergoing EMR, esophagectomy, or colectomy. Proflavine hemisulfate, a vital fluorescent dye, was applied topically. The specimens were imaged with a widefield multispectral microscope and a high-resolution microendoscope. The images were compared with histopathologic examination. RESULTS: Widefield fluorescence imaging enhanced visualization of morphology, including the presence and spatial distribution of glands, glandular distortion, atrophy, and crowding. High-resolution imaging of widefield abnormal areas revealed that neoplastic progression corresponded to glandular heterogeneity and nuclear crowding in dysplasia, with glandular effacement in carcinoma. These widefield and high-resolution image features correlated well with the histopathologic features. LIMITATIONS: This imaging approach must be validated in vivo with a larger sample size. CONCLUSIONS: Multiscale proflavine-enhanced fluorescence imaging can delineate epithelial changes in a variety of GI conditions. Distorted glandular features seen with widefield imaging could serve as a critical bridge to high-resolution probe placement. An endoscopic platform combining the two modalities with a single vital dye may facilitate point-of-care decision making by providing real-time, in vivo diagnoses. PMID- 22301344 TI - Intraductal aspiration: a promising new tissue-sampling technique for the diagnosis of suspected malignant biliary strictures. AB - BACKGROUND: Brushing is the most commonly used technique for biliary sampling at ERCP, despite its limited sensitivity. OBJECTIVE: To evaluate intraductal aspiration (IDA) as a new combined endoscopic technique for cytodiagnosis, its cellular adequacy, diagnostic accuracy for cancer detection, feasibility, and safety. DESIGN: Prospective, observational study. SETTING: Single tertiary referral center. MAIN OUTCOME MEASUREMENTS: IDA cellular adequacy, diagnostic accuracy for cancer detection, feasibility, and safety. PATIENTS AND METHODS: From April 2009 to September 2010, 42 consecutive patients with suspected malignant biliary stricture underwent ERCP, with tissue sampling obtained with IDA. IDA included performance of standard brushing in all patients. After standard brushing, to perform IDA, we removed the brush from its catheter and used the tip of the catheter as a scraping device. The tip was scraped back and forth across the stricture at least 10 times. The catheter and a suction line were connected to a specimen trap to obtain intraductal aspiration of fluids and samplings. RESULTS: Our cytopathologists found adequate cellular yield in 39 of the 42 IDA samples (92.8%) versus 15 of the 42 brushing samples (35.7%) (P < .001). IDA showed a significantly higher sensitivity than brushing (89% vs 78% for adequate samples and 89% vs 37% for all samples) and provided significantly superior cellular adequacy (92.8% vs 35.7%). LIMITATIONS: Observational study, small number of patients. CONCLUSIONS: IDA significantly improves brushing cellular adequacy and has high sensitivity for cancer detection. It was also safe, simple, rapid, and applicable during routine diagnostic ERCP, with no additional costs. PMID- 22301345 TI - Dose-dependent depth of tissue injury with carbon dioxide cryotherapy in porcine GI tract. AB - BACKGROUND: Cryotherapy is a method of endoscopic mucosal ablation that involves delivery of a cryogen to result in tissue destruction by extreme low temperature. Its effects are influenced by the dosage of cryogen and thawing of ice. There are limited data on the tissue effects of multiple freeze and thaw cycles of carbon dioxide (CO(2)) cryotherapy on GI tissues. OBJECTIVE: To investigate the extent of tissue injury due to escalating doses of CO(2) cryotherapy on the esophagus, stomach, and colon of pigs. DESIGN: Animal experiment. INTERVENTION: Varying doses of CO(2) cryotherapy with increasing number of freeze-thaw cycles were applied to each site. The animals were allowed to survive for 48 hours. MAIN OUTCOME MEASUREMENTS: Depth of tissue injury assessed in blinded fashion by varying doses of cryotherapy on a defined area of porcine esophagus, stomach, and colon. RESULTS: There was a dose-dependent relationship of CO(2) cryogen and depth of injury (P = .0001 and P = .002, respectively). In the stomach, the dose response relationship was significant (P = .007), but the average grades of injury across the various doses were lower when compared with the esophagus at comparable cryogen doses (P = .0004). The estimated depth of tissue injury from the mucosal surface in the porcine esophagus and colon tissue ranged from 1.2 to 2.5 mm and 1.3 to 2.5 mm, respectively. LIMITATIONS: The study was performed in a normal porcine model. CONCLUSION: There was a dose-dependent relationship between the dose of CO(2) cryotherapy and the depth of tissue injury in the porcine esophagus, stomach, and colon. PMID- 22301346 TI - Injectable drug-eluting elastomeric polymer: a novel submucosal injection material. AB - BACKGROUND: Biodegradable hydrogels can deliver therapeutic payloads with great potentials in EMR and endoscopic submucosal dissection (ESD) to yield improvements in efficacy and foster mucosal regeneration. OBJECTIVE: To assess the efficacy of an injectable drug-eluting elastomeric polymer (iDEEP) as a submucosal injection material. DESIGN: Comparative study of 3 different solutions by using material characterization tests and ex vivo and in vivo porcine models. SETTING: Academic hospital. INTERVENTIONS: Thirty gastric submucosal cushions were achieved with saline solution (0.9%), sodium hyaluronate (0.4%), and iDEEP (n = 10) in ex vivo porcine stomachs. Four porcine gastric submucosal cushions were then created in vivo by using iDEEP. MAIN OUTCOME MEASUREMENTS: Maximum injection pressure, rebamipide release rate, submucosal elevation duration, and assessment of in vivo efficacy by en bloc resection. RESULTS: No significant difference in injection pressures between iDEEP (28.9 +/- 0.3 psi) and sodium hyaluronate (29.5 +/- 0.4 psi, P > .05) was observed. iDEEP gels displayed a controlled release of rebamipide up to 2 weeks in vitro. The elevation height of iDEEP (5.7 +/- 0.5 mm) was higher than that of saline solution (2.8 +/- 0.2 mm, P < .01) and sodium hyaluronate (4.2 +/- 0.2 mm, P < .05). All EMR procedures were successfully performed after injection of iDEEP, and a large gel cushion was noted after the resection procedure. LIMITATIONS: Benchtop, ex vivo, and nonsurvival pig study. CONCLUSIONS: A novel injection solution was evaluated for endoscopic resection. These results suggest that iDEEP may provide a significant step toward the realization of an ideal EMR and endoscopic submucosal dissection injection material. PMID- 22301347 TI - Clinical evaluation of a novel lumen-apposing metal stent for endosonography guided pancreatic pseudocyst and gallbladder drainage (with videos). AB - BACKGROUND: Tubular plastic and metal stents have inherent shortcomings when used for transenteric drainage of fluid collections. OBJECTIVE: To evaluate a novel lumen-apposing, self-expandable metal stent for EUS-guided drainage of pancreatic pseudocysts and the gallbladder. DESIGN: Retrospective case series. SETTING: Tertiary-care academic medical center. PATIENTS: This study involved 15 patients (median age 54 years) with symptomatic pancreatic pseudocysts who underwent 12 transgastric and 3 transduodenal pseudocyst drainage procedures. Five patients (median age 69.5 years) with acute cholecystitis underwent 4 cholecystoduodenostomies and 1 cholecystogastostomy. INTERVENTION: Stent deployment under EUS guidance, passage of an endoscope through the stent lumen for pseudocystoscopy or cholecystoscopy, transenteric endoscopy-guided interventions including biopsy, necrosectomy, and stone removal. MAIN OUTCOME MEASUREMENTS: Technical and clinical success. RESULTS: All stents were successfully deployed without complication, with a median time to removal of 35 days. All pseudocysts resolved after a single drainage procedure. One stent migrated into the stomach, and the remaining 14 were found to be patent at the time of removal. There was no pseudocyst recurrence during the 11.4-month median follow-up period. One gallbladder stent remains indwelling and fully patent at 12 months. Resolution of acute cholecystitis was observed immediately after stent implantation. No recurrence of symptoms was observed during a median follow-up period of 9 months. LIMITATIONS: Retrospective study, small sample size, lack of control patients. CONCLUSION: Transenteric drainage of pancreatic pseudocysts and the gallbladder by using a novel, lumen-apposing, metal stent was accomplished with high technical and clinical success in this pilot observational study. Further studies are warranted. PMID- 22301348 TI - Generation of induced pluripotent stem cells from skin fibroblasts of a patient with olivopontocerebellar atrophy. AB - Generation of induced pluripotent stem (iPS) cells from somatic cells of patients represents a powerful tool for disease modeling, and they may have a wide range of applications in cell therapies. Olivopontocerebellar atrophy (OPCA) is a rare and debilitating neurologic disease of insidious onset, characterized by atrophy of the cerebellum pons and inferior olivary nuclei with concomitant ambulation deficits and dyscoordination. Here, we report the generation of iPS cells from skin fibroblasts of a 56-year-old female patient with familial OPCA. OPCA is classified in the autosomal dominant ataxia that is also named spinocerebellar ataxia (SCA) 7. The disease allele of SCA7 gene of the patient contains 45 CAG trinucleotide repeats, the number of which is larger than the normal repeat number (4 to 36 CAG repeats). The OPCA-iPS cells were generated via ectopic expression of four transcription factors: OCT4, SOX2, KLF4 and c-MYC. The OPCA iPS cells expressed the pluripotency markers, and they can be differentiated into various somatic cell types in vitro and in vivo. Furthermore, the iPS cells also can be committed to differentiate into neural cells. Therefore, the OPCA-iPS cells offer an unprecedented cell model to investigate disease mechanisms, discover novel drugs, and develop new therapies for OPCA. PMID- 22301349 TI - Loss in risk-taking: absence of optimal gain or reduction in one's own resources? AB - Determining how living beings react to tasks that reflect realistic situations of risk has given rise to a vast literature. However, I argue that the methodologies traditionally used to test humans and nonhumans relative to risk often fail to achieve their goal. When risk is modelled in laboratory, potential decision cost (or potential loss) typically denotes an absence of optimal gain. In contrast, when risk occurs in real-life situations, potential loss denotes the reduction in an individual's limited resources - whether energetic, social, financial, etc. This conceptual difference about the nature of risk may have important implications for the understanding of the parameters that control risk-taking behaviour. PMID- 22301350 TI - Effects of nicotine exposure on locomotor activity and pCREB levels in the ventral striatum of adolescent rats. AB - Behavioral reactivity to novel stimuli, which is greater in the adolescent than young adult population, is associated with drug abuse liability, suggesting that the increased addiction vulnerability of adolescents may be related to heightened novel stimulus reactivity and underlying cellular processes. We examined the hypothesis that adolescent animals who exhibit higher novel stimulus reactivity, exhibit greater locomotor activity in response to nicotine than adolescents who exhibit lower novel stimulus reactivity, and that this difference is associated with alterations in CREB expression and activity in the ventral striatum (vStr) and prefrontal cortex (PFC). Adolescents exhibiting high locomotor activity (HLA) in the novel open field developed tolerance to the locomotor depressant effects of nicotine with fewer exposures and at lower doses than adolescents with low locomotor activity (LLA). Further, HLA adolescents exhibited lower CREB activity in the vStr than LLA adolescents and this difference was attenuated by repeated exposure to high, but not low doses of nicotine. Thus, inherent differences in the reactivity to novel stimulation during the adolescent period appear to predict sensitivity to the behavioral and cellular effects of nicotine and may underlie differences in progression to addiction. PMID- 22301351 TI - The salience network contributes to an individual's fluid reasoning capacity. AB - Fluid reasoning is the ability to think flexibly and logically, analyze novel problems and identify the relationships that underpin these problems independent of acquired knowledge. Although many functional imaging studies have investigated brain activation during fluid reasoning tasks, the neural correlates of fluid reasoning remain elusive. In the present study, we aimed to uncover the neural correlates of fluid reasoning by analyzing correlations between Raven's Standard Progressive Matrices (RSPM), an effective measure of fluid reasoning, and measures of regional gray matter volume (GMV) and regional homogeneity (ReHo) in a voxel-wise manner throughout the whole brain in 297 healthy young adults. The most important finding was that RSPM scores were positively correlated with both GMV and ReHo values in brain areas that belong to the salience network, including the dorsal anterior cingulate cortex and the fronto-insular cortex. Additionally, we found positive or negative correlations between RSPM scores and GMV or ReHo values in brain areas of the central-executive, default-mode, sensorimotor and visual networks. Our findings suggest that fluid reasoning ability is related to a variety of brain areas and emphasize the important contribution of the salience network to this ability. PMID- 22301352 TI - Fos expression in the orbital prefrontal cortex after exposure to the fixed interval peak procedure. AB - It has been proposed that cortico-striato-thalamo-cortical circuits that incorporate the prefrontal cortex and dorsal striatum regulate interval timing behaviour. The present experiment examined whether performance on the fixed interval peak procedure (FIPP), an immediate timing schedule, would induce neuronal activity in cortical and striatal areas, as revealed by enhanced expression of the Fos protein, a marker for neuronal activation. Regional Fos expression was compared between rats trained on the FIPP and rats trained on a variable-interval (VI) schedule matched to the FIPP for overall response rate and reinforcer delivery. Response rate in the peak trials of the FIPP conformed to a temporally differentiated pattern, which was well described by a modified Gaussian function; in agreement with previous findings, the peak time occurred close to the time at which the reinforcer was delivered in the fixed-interval trials, and the Weber fraction was within the range of values reported previously. The density of Fos-positive neurones (counts mm(-2)) in the orbital prefrontal cortex (OPFC) was greater in rats exposed to the FIPP than in rats exposed to the VI schedule, suggesting a greater activation of this area during the performance of the former task. This is consistent with the results of previous studies that have implicated the OPFC in interval timing behaviour. However, there was no significant difference between the levels of Fos expression in the dorsal or ventral striatum of the rats trained under the two schedules. PMID- 22301353 TI - Functional mannose-binding lectin levels in patients with end-stage renal disease on maintenance hemodialysis. AB - BACKGROUND: Innate immunity is generally impaired in chronic renal failure (CRF). Mannose-binding lectin (MBL) has an important role in first-line host defense against pathogens via the lectin pathway. We recently reported that functional MBL was significantly lower in CRF patients than in healthy subjects. In this study, we aimed to determine whether functional MBL would be improved following hemodialysis (HD) therapy. METHODS: This study included 22 patients with end stage renal disease (ESRD) on maintenance HD. Functional MBL was measured every 6 months for 1 year after HD using an enzyme-linked immunosorbent assay. RESULTS: Median serum functional MBL levels of ESRD patients were significantly higher after 6 and 12 months than at the start of HD therapy (p < 0.05 and p < 0.01, respectively). Furthermore, median functional MBL levels at 12 months were significantly higher than those at 6 months (p < 0.05). CONCLUSIONS: We found significant increases in serum functional MBL levels in patients on HD. Our results indicated that HD tailored to remove uremic toxins could improve functional MBL levels in these patients. PMID- 22301354 TI - Rhinoconjunctivitis prevalence and associated factors in school children aged 6-7 and 13-14 years old in Bogota, Colombia. AB - OBJECTIVE: Allergic rhinitis is one of the most frequent chronic diseases among children. The objective of the study was to assess the prevalence of rhinoconjunctivitis and determine clinical, social and environmental associated factors, among school children aged 6-7 years and adolescents aged 13-14 years in Bogota, Colombia. METHODS: We used ISAAC (International Study of Asthma and Allergies in Childhood) phase III study methodology and questionnaire for design and data collection, and we did a secondary analysis of these data. The sample consisted of 3830 registers from adolescents between 13 and 14 years old and 3256 registers from children between 6 and 7 years. RESULTS: The prevalence of rhinoconjunctivitis symptoms in the last year was 17.2% (95% CI, 15.9-18.5) in children vs. 24.9% (95% CI, 23.6-26.3) in adolescents. In both groups there was a female predominance in children (17.8% vs. 16.5%), and in the teenagers group (28.0% vs. 21.4%), though the differences were not statistically significant. The factors associated with rhinoconjunctivitis in the group of 6-7 years where: asthma [OR 3.9; (95% CI, 2.8-5.4)], atopic dermatitis [OR 2.3; (95% CI, 1.7 3.1)], use of acetaminophen in the last year [OR 2.6; (95% CI, 1.4-4.9)], use of antibiotics in the first year of live [OR 1.7; (95% CI, 1.3-2.3)], higher maternal education [OR 1.5; (95% CI, 1.0-2.3)] and cesarean delivery [OR 1.6; (95% CI, 1.2-2.1)]. Among the 13-14 year age-group, factors associated with rhinoconjunctivitis included: asthma [OR 2.6; (95% CI, 2.0-3.4)], atopic dermatitis [OR 1.8; (95% CI, 1.4-2.3)], use of acetaminophen in the last year [OR 1.8; (95% CI, 1.4-2.4)], consumption of fast-food three times or more per week [OR 1.5; (95% CI, 1.2-2.0), ever smoked [OR 1.4; (95% CI, 1.2-1.7)] and meat consumption was protective factor [OR 0.7; (95% CI, 0.5-0.9)]. CONCLUSION: In both studied groups, the estimated prevalence of rhinoconjunctivitis symptoms was relatively high. Future in-depth research is needed to assess the complex interactions between allergic rhinoconjunctivitis symptoms and social and environmental factors. PMID- 22301355 TI - A case of Klippel-Feil syndrome with congenital enlarged Eustachian tube. AB - The Klippel-Feil syndrome is a congenital anomaly characterized by fusion of the cervical vertebrae. It is often associated with serious congenital anomalies of the nervous, cardiovascular and urogenital systems. One of the anomalies which have not been thoroughly investigated to date are that accompanying Klippel-Feil syndrome and enlarged Eustachian tube. We report a case of type III Klippel-Feil syndrome with associated rib anomalies such as hypoplastic and bifid ribs, scoliosis and elevated scapula (Sprengel's disease). The patient also presented hemifacial microsomia and central facial palsy of the lower right side of the face, urogenital and cardiovascular anomaly, congenital anorectal atresia and right-sided congenital aural atresia with microtia. Computer tomography of temporal bone showed abnormal extension of the right Eustachian tube with anomalies of the middle and inner ear on this particular side. In this case report we discuss the associated anomalies of the patient with Klippel-Feil syndrome. The aim of this case report is to draw attention to very rare case of patient with Klippel-Feil syndrome and enlarged pharyngotympanic tube. PMID- 22301356 TI - Spinodal decomposition of polymer solutions: molecular dynamics simulations of the two-dimensional case. AB - As a generic model system for phase separation in polymer solutions, a coarse grained model for hexadecane/carbon dioxide mixtures has been studied in two dimensional geometry. Both the phase diagram in equilibrium (obtained from a finite size scaling analysis of Monte Carlo data) and the kinetics of state changes caused by pressure jumps (studied by large scale molecular dynamics simulations) are presented. The results are compared to previous work where the same model was studied in three-dimensional geometry and under confinement in slit geometry. For deep quenches the characteristic length scale l(t) of the formed domains grows with time t according to a power law close to [Formula: see text]. Since in this problem both the polymer density rho(p) and the solvent density rho(s) matter, the time evolution of the density distribution P(L)(rho(p),rho(s),t) in L * L subboxes of the system is also analyzed. It is found that in the first stage of phase separation the system separates locally into low density carbon dioxide regions that contain no polymers and regions of high density polymer melt that are supersaturated with this solvent. The further coarsening proceeds via the growth of domains of rather irregular shapes. A brief comparison of our findings with results of other models is given. PMID- 22301357 TI - Catastrophic failure of hip arthroscopy due to iatrogenic instability: can partial division of the ligamentum teres and iliofemoral ligament cause subluxation? AB - Hip arthroscopy is an evolving surgical tool, and with any new procedure, it is important to learn from the complications encountered. A patient with mild hip dysplasia and a symptomatic labral tear underwent uneventful hip arthroscopy and labral repair including partial debridement of a hypertrophied ligamentum teres. Despite preservation of the labrum, no pincer resection, and a modest capsulotomy, 3 months, subluxation and joint space narrowing were noted. One year, end-stage arthritis was present, requiring total hip replacement. Instability after hip arthroscopy is due to a number of factors, including excessive rim trimming, capsulotomy, overzealous labral resection, or inadequate labral repair. This report emphasizes the importance of the ligamentum teres and small disruptions of the capsule in patients with mild dysplasia. PMID- 22301358 TI - Anterior cruciate ligament femoral footprint anatomy: systematic review of the 21st century literature. AB - PURPOSE: The purpose of our study was to systematically review current arthroscopic and related literature and to characterize the anatomic centrum of the anterior cruciate ligament (ACL) femoral footprint. METHODS: On June 2, 2011, 2 independent reviewers performed a Medline search using the terms "anterior cruciate ligament" or "ACL," "femur" or "femoral," and "anatomy" or "origin" or "footprint." We included anatomic, cadaveric, and radiographic studies of adult, human, ACL femoral anatomy. Studies not published in the English language, studies published before January 1, 2000, and review articles were excluded. References of included articles were also searched according to our inclusion/exclusion criteria. Included studies were subjectively and quantitatively synthesized to define the anatomic centrum of the ACL femoral footprint. RESULTS: The Medline search produced 533 articles. After application of inclusion and exclusion criteria and reference search, 20 articles were included and systematically reviewed. With regard to arthroscopically measurable landmarks, the anatomic centrum of the ACL femoral footprint is, on average, (1) in the sagittal plane, 43% of the distance from the proximal articular margin (arthroscopically visualized osteochondral junction) to the distal articular margin on the lateral wall of the intercondylar notch, and (2) in the axial plane, socket radius plus 2.5 mm anterior to the posterior articular margin, with a 2.5-mm rim of bone between the posterior ACL fibers and the posterior articular cartilage margin. CONCLUSIONS: Our results show that the anatomic centrum of the ACL femoral footprint is 43% of the proximal-to-distal length of lateral, femoral intercondylar notch wall and femoral socket radius plus 2.5 mm anterior to the posterior articular margin. CLINICAL RELEVANCE: This systematic review of basic science studies may have clinical relevance for surgeons who believe that anatomic ACL reconstruction can result in improved outcomes. PMID- 22301359 TI - Anterior cruciate ligament tibial footprint anatomy: systematic review of the 21st century literature. AB - PURPOSE: The purpose of this study was to systematically review current arthroscopic and related literature and to characterize the anatomic centrum of the anterior cruciate ligament (ACL) tibial footprint. METHODS: On January 31, 2011, 2 independent reviewers performed a Medline search using the terms "anterior cruciate ligament" or "ACL," "tibia" or "tibial," and "anatomy" or "footprint." We included anatomic, cadaveric, and radiographic studies of adult, human, ACL tibial anatomy. Studies not published in the English language, studies published before January 1, 2000, and review articles were excluded. References of included articles were also searched according to our inclusion/exclusion criteria. Included studies were subjectively synthesized, to define the anatomic centrum of the ACL tibial footprint. RESULTS: The Medline search produced 1,224 articles. After application of our inclusion and exclusion criteria and additional search of article references, 19 articles were included and systematically reviewed. With regard to arthroscopically relevant landmarks, (1) in the anterior-to-posterior plane, the anatomic centrum of the ACL tibial footprint as a whole is 15 mm anterior to the posterior cruciate ligament (PCL), the anatomic centrum of the anteromedial bundle is 20 mm anterior to the PCL, and the anatomic centrum of the posterolateral bundle is 11 mm anterior to the PCL and (2) in the medial-to-lateral (ML) plane, the anatomic centrum of the ACL tibial footprint as a whole is two-fifths the ML width of the interspinous distance, the anatomic centrum of the anteromedial bundle is one-half the ML width of the interspinous distance, and the anatomic centrum of the posterolateral bundle is one-fourth the ML width of the interspinous distance. CONCLUSIONS: Our results show that the anatomic centrum of the ACL tibial footprint is 15 mm anterior to the PCL and two-fifths the ML width of the interspinous distance. CLINICAL RELEVANCE: This systematic review of basic science studies may have clinical relevance for surgeons who believe that anatomic ACL reconstruction can result in improved outcomes. PMID- 22301360 TI - Biomechanical evaluation of classic solid and novel all-soft suture anchors for glenoid labral repair. AB - PURPOSE: To evaluate the biomechanical performance of an all-soft suture anchor (JuggerKnot; Biomet, Warsaw, IN) in comparison with a classic solid suture anchor (2.4-mm biocomposite SutureTak; Arthrex, Naples, FL) in an in vitro labral repair model. METHODS: We dissected 12 cadaveric shoulders (mean age, 61 +/- 9.4 years), leaving the labrum intact, and bone mineral density was obtained (mean, 0.375 +/- 0.06 g/cm(3)). Simulated labral tears were made at the anteroinferior and posteroinferior edges of the labrum. Repairs used 2 all-soft suture anchors (JuggerKnot) or 2 solid anchors with free, high-strength No. 2 suture (FiberWire; Arthrex) spanning the operative construct to load the repair. Differential variable reluctance transducers were used to measure labral displacement for each specimen. The testing protocol consisted of a preconditioning phase at 10 N for 10 cycles (1 Hz) and then a final load-to-failure testing at a rate of 3 mm/min. Labral displacement of 2 mm was determined as the primary outcome. RESULTS: There was no statistical difference (P = .22) in ultimate load to failure and displacement at ultimate failure (anchor pullout) between the all-soft JuggerKnot (146.0 +/- 43.0 N and 19.8 +/- 5.4 mm, respectively) and the solid SutureTak (171.9 +/- 52.6 N and 22.3 +/- 6.8 mm, respectively). The solid anchor had a significantly higher ultimate load at 2 mm of labral displacement than the all soft suture anchor (84.1 +/- 19.0 N and 39.2 +/- 10.6 N, respectively; P < .001). CONCLUSIONS: Whereas both the solid SutureTak and the all-soft JuggerKnot displayed similar results on ultimate load-to-failure testing, the solid anchor required significantly greater load for 2 mm of labral displacement than the all soft anchor. CLINICAL RELEVANCE: The all-soft anchor (JuggerKnot) is similar in biomechanical performance to the classic solid anchor (SutureTak) with the exception of load at 2 mm of labral displacement, suggesting micromotion of the device. PMID- 22301361 TI - Open lateral patellar retinacular lengthening versus open retinacular release in lateral patellar hypercompression syndrome: a prospective double-blinded comparative study on complications and outcome. AB - PURPOSE: To compare complication rates and outcome of open lateral retinacular (LR) lengthening and open LR release in the treatment of lateral patellar hypercompression syndrome (LPHS). METHODS: In a prospective double-blinded study, 28 patients (mean age, 48 years; 21 women and 7 men) received either LR release (14 patients) or LR lengthening (14 patients) in alternating fashion over the same lateral parapatellar skin incision for LPHS (blinding of patients to surgical procedure [i.e., single blinding]). Strict inclusion criteria (retinacular pain, tight retinaculum, decreased patellar mobility) were used to exclude other reasons for anterior knee pain (patellar instability, leg malalignment or maltorsion, trochlear dysplasia, patella alta). The surgeon and postsurgical rehabilitation were the same. Preoperatively and at 3, 6, 12, and 24 months postoperatively, complications, muscle atrophy, and Kujala patellofemoral outcome score were documented by examiners blinded to the surgical procedure (double blinding). All patients completed 2 years of follow-up. RESULTS: The results of 2 years of follow-up showed that recurrence of LPHS, as indicated by the patellar tilt test and decreased medial patellar glide test, developed in 2 cases after LR release and 1 case after LR lengthening (P > .999). Medial patellar subluxation, as indicated by the gravitation-subluxation test and increased medial patellar glide test, developed in 5 cases after LR release and no case after LR lengthening (P = .041). Quadriceps atrophy, as indicated by the mean circumference difference compared with the healthy contralateral side, was significantly higher (P = .001) in the LR release group (1.8 cm) than in the LR lengthening group (0.2 cm). The mean Kujala score was significantly lower (P = .035) in the LR release group (77.2 points) than in the LR lengthening group (88.4 points). CONCLUSIONS: In this prospective double-blinded study, retinacular lengthening showed less medial instability, less quadriceps atrophy, and a better clinical outcome at 2 years compared with retinacular release. We believe that this may be explained by the controlled preservation of the lateral patellar muscle-capsuloligamentous continuity after retinacular lengthening. LEVEL OF EVIDENCE: Level II, prospective double-blinded comparative study. PMID- 22301362 TI - Femoral anteversion in the hip: comparison of measurement by computed tomography, magnetic resonance imaging, and physical examination. AB - PURPOSE: The purpose of this study was to evaluate the correlation between computed tomography (CT) and magnetic resonance imaging (MRI) measurements of femoral anteversion, as well as the relation of anteversion with physical examination and radiographic findings. METHODS: Preoperative CT and MRI measurements of anteversion along with clinical examination were performed on 129 consecutive hips before hip arthroscopy for nonarthritic hip injuries. All anteversion measurements were performed by 2 musculoskeletal radiologists. The radiographic findings and physical examination findings were analyzed for statistically significant correlations. For statistical analysis purposes, the patients were divided into 3 groups according to the mean CT anteversion measurement: group I (low), less than 10 degrees ; group II (medium), 10 degrees to 22 degrees ; and group III (high), greater than 22 degrees . RESULTS: High interobserver correlation was found for femoral anteversion measurement by CT and MRI (r = 0.95 and r = 0.86, respectively; P < .0001 for both). CT and MRI measurements showed high correlation with each other (r = 0.80, P < .0001). However, in 96% of the cases, the CT measurement was larger, with a mean difference of 8.9 degrees (range, -37 degrees to 1.5 degrees ). A significant correlation coefficient was found between internal rotation and anteversion angles as measured by CT (r = 0.36, P < .0001). However, no correlation was found with other hip movement measurements. Abnormal femoral acetabular bony architecture of the hip was found in 64% of the patients; isolated cam impingement was more prevalent in group I, whereas isolated pincer impingement was more prevalent in group III (P = .01). CONCLUSIONS: Although high correlation was found between anteversion angle measurements by CT and MRI, significant discrepancies in the absolute anteversion number between the 2 techniques suggest that they may not be interchangeable. Furthermore, CT was found to have higher interobserver reliability than MRI. There was a significant correlation between CT and examination of internal rotation of the hip. Clinically, the findings of the study show that the diagnosis of excessive femoral anteversion or retroversion should have different thresholds according to MRI and CT measurements; moreover, the diagnosis should not rely exclusively on either examination or radiologic criteria. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 22301363 TI - Arthroscopic side-to-side repair of massive and contracted rotator cuff tears using a single uninterrupted suture: the shoestring bridge technique. AB - PURPOSE: This study was performed to evaluate the clinical effectiveness of a new side-to-side repair technique for massive rotator cuff tears using a single uninterrupted suture in the configuration of a shoestring in a medial-to-lateral progression. METHODS: Thirty-one consecutive patients with a mean age of 59 years (SD, 4.7 years) had primary arthroscopic repair of their massive, U-shaped, contracted supraspinatus and infraspinatus tear by the shoestring bridge technique. Preoperatively and postoperatively, we measured active forward flexion and determined the visual analog scale score for pain, Simple Shoulder Test score, and Disabilities of the Arm, Shoulder and Hand (DASH) score. Repair integrity was evaluated by ultrasonography. RESULTS: At a mean follow-up of 26.5 months, all scores had significantly improved: active forward flexion, mean of 70 degrees (SD, 29 degrees ) preoperatively to 139 degrees (SD, 39 degrees ) postoperatively (P < .001); visual analog scale score for pain, 8.0 +/- 1.4 points to 2.5 +/- 1.8 points (P < .001); Simple Shoulder Test score, 15% +/- 19% to 72% +/- 23% (P < .001); and Disabilities of the Arm, Shoulder and Hand score, 62 +/- 17 points to 21 +/- 14 points (P < .001). Ultrasound evaluation showed that 25 of 31 patients (81%) had heeled tendons. Of 31 patients, 6 (19%) had a complete retear. Only 3 of these 6 patients were not satisfied with the result. CONCLUSIONS: Arthroscopic side-to-side repair by the shoestring bridge technique is effective in the treatment of massive, U-shaped, contracted supraspinatus and infraspinatus tears. It provides the shoulder surgeon a treatment modality with significant improvement in pain and function, high patient satisfaction, and a low retear rate. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 22301364 TI - Potent immune activation in chronic hepatitis C patients upon administration of an oral inducer of endogenous interferons that acts via Toll-like receptor 7. AB - BACKGROUND: ANA773, an oral prodrug of a small-molecule Toll-like receptor (TLR)7 agonist, induces a dose-related decrease in serum HCV RNA levels in chronic hepatitis C patients. METHODS: The prodrug ANA773 was administered to healthy individuals and chronic hepatitis C patients. At different time points during the course of treatment, modulation of the phenotype and function of peripheral leukocytes were evaluated to determine the role of distinct immune cells on the clinical outcome of therapy. RESULTS: Early after administration of the TLR7 agonist, a mild transient reduction of the number of lymphocytes was observed in both healthy individuals and chronic hepatitis C patients. Moreover, repeated administration of ANA773 resulted in transiently reduced numbers of myeloid and plasmacytoid dendritic cells (DC) in blood. Interestingly, reduced plasmacytoid DC numbers as well as increased serum interferon (IFN)-alpha and IFN-gamma inducible protein (IP)-10 levels were observed only in virological responders (>=1 log(10) IU/ml reduction of HCV RNA levels upon ANA773 treatment), but were absent in virological non-responders. In vitro stimulation of peripheral blood mononuclear cells from virological responders showed a high frequency of IFN alpha-producing plasmacytoid DC upon stimulation in vitro with ANA773, whereas no IFN-alpha was induced in non-responders. CONCLUSIONS: These findings indicate that the viral load decline in chronic hepatitis C patients treated with the TLR7 agonist ANA773 is likely due to intrinsic differences in the induction of endogenous IFNs and IFN-stimulated gene products (IFN-alpha and IP-10) upon TLR7 ligation. PMID- 22301365 TI - The effect of dimensionality on growth and differentiation of neural progenitors from different regions of fetal rat brain in vitro: 3-dimensional spheroid versus 2-dimensional monolayer culture. AB - Three-dimensional (3-D) spheroids are widely used for culturing cells. However, 2 dimensional (2-D) monolayer cultures have also been adopted for culture and used in a broad range of cell biology studies. To address the effect of dimensionality on the growth and differentiation of neuroprogenitor cells in 3-D spheroids and 2 D monolayer cultures, cells were isolated from cerebral cortex, cerebella and brainstem of fetal rat brain then cultured in serum-free DMEM/F12 medium or DMEM with 10% FBS. The growth and differentiation of neuroprogenitor cells from three brain regions in spheroids was compared with that in monolayer cultures, and the differentiation components of neuroprogenitor cells were compared with in vivo brain sections. Neuroprogenitor cells in spheroids proliferate actively over 10 days in culture as showed by Ki67 incorporation and increase in spheroid diameter. More neuroprogenitor cells underwent neuronal differentiation in spheroids than in monolayer cultures. In comparison with fixed rat brain sections, the neuron to astrocyte ratio, as shown by neurofilament to glial fibrillary acidic protein immunoreactivity, in spheroids is similar to that found in adult rat tissue sections. Our results suggest that the spheroid culture system mimics the in vivo cytoarchitecture to a greater extent and more closely reflects the cellular composition in adult brain tissue. This supports the notion that the intercellular niche in spheroids is more favorable for the survival and differentiation of neuronal precursors, while the cues in monolayer cultures may favor glial cell survival. It is therefore concluded that dimensionality plays a significant role in determining cellular behavior in vitro. PMID- 22301366 TI - DNA immobilization and detection on cellulose paper using a surface grown cationic polymer via ATRP. AB - Cationic polymers with various structures have been widely investigated in the areas of medical diagnostics and molecular biology because of their unique binding properties and capability to interact with biological molecules in complex biological environments. In this work, we report the grafting of a linear cationic polymer from an atom transfer radical polymerization (ATRP) initiator bound to cellulose paper surface. We show successful binding of ATRP initiator onto cellulose paper and grafting of polymer chains from the immobilized initiator with ATRP. The cellulose paper grafted polymer was used in combination with PicoGreen (PG) to demonstrate detection of nucleic acids in the nanogram range in homogeneous solution and in a biological sample (serum). The results showed specific identification of hybridized DNA after addition of PG in both solutions. PMID- 22301368 TI - Comparison of biolimus eluted from an erodible stent coating with bare metal stents in acute ST-elevation myocardial infarction (COMFORTABLE AMI trial): rationale and design. AB - AIMS: Compared with bare metal stents (BMS), early generation drug-eluting stents (DES) reduce the risk of revascularisation in patients with ST-elevation myocardial infarction (STEMI) at the expense of an increased risk of very late stent thrombosis (ST). Durable polymer coatings for controlled drug release have been identified as a potential trigger for these late adverse events and this has led to the development of newer generation DES with durable and biodegradable polymer surface coatings with improved biocompatibility. In a recent all-comers trial, biolimus-eluting stents with a biodegradable polymer surface coating were found to reduce the risk of very late ST by 80% compared with sirolimus-eluting stents with durable polymer, which also translated into a lower risk of cardiac death and myocardial infarction (MI) beyond one year. METHODS AND RESULTS: The multicentre COMFORTABLE AMI trial (NCT00962416) randomly assigned 1,161 patients to treatment with biolimus-eluting stents with biodegrable polymer and bare metal stents of otherwise identical design at 11 international sites. The primary endpoint is a composite of cardiac death, target-vessel MI and target lesion revascularisation at one year. Assuming a relative risk reduction of 40% in event rates of the primary endpoint in favour of biolimus-eluting stents with biodegradable polymer, 1,064 patients will provide 80% power to demonstrate superiority. Clinical follow-up will be continued through five years. CONCLUSIONS: The COMFORTABLE AMI trial will determine whether biolimus-eluting stents with biodegradable polymer are superior to bare metal stents of otherwise identical design. This is the first randomised controlled trial (RCT) investigating DES with a biodegradable polymer surface coating for drug release in the treatment of patients with STEMI. PMID- 22301369 TI - A metabolomics approach to characterise and identify various Mycobacterium species. AB - We investigated the potential use of gas chromatography mass spectrometry (GC MS), in combination with multivariate statistical data processing, to build a model for the classification of various tuberculosis (TB) causing, and non-TB Mycobacterium species, on the basis of their characteristic metabolite profiles. A modified Bligh-Dyer extraction procedure was used to extract lipid components from Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium bovis, and Mycobacterium kansasii cultures. Principle component analyses (PCA) of the GC-MS generated data showed a clear differentiation between all the Mycobacterium species tested. Subsequently, the 12 compounds best describing the variation between the sample groups were identified as potential metabolite markers, using PCA and partial least-squares discriminant analysis (PLS-DA). These metabolite markers were then used to build a discriminant classification model based on Bayes' theorem, in conjunction with multivariate kernel density estimation. This model subsequently correctly classified 2 "unknown" samples for each of the Mycobacterium species analysed, with probabilities ranging from 72 to 100%. Furthermore, Mycobacterium species classification could be achieved in less than 16 h, and the detection limit for this approach was 1*10(3)bacteriamL(-1). This study proves the capacity of a GC-MS, metabolomics pattern recognition approach for its possible use in TB diagnostics and disease characterisation. PMID- 22301370 TI - Function and biochemical characterization of RecJ in Deinococcus radiodurans. AB - The single-stranded DNA-specific nuclease RecJ is found in most bacteria where it is involved in the RecFOR double-stranded break (DSBs) repair pathway. DSBs repair mainly occurs via the RecFOR pathway in Deinococcus radiodurans, a well known radiation-resistant bacterium. A recJ null mutant was constructed to investigate the role of recJ in D. radiodurans. recJ inactivation caused growth defects and sensitivity to high temperatures. However, the radiation resistance of the recJ mutant was only moderately decreased. The full-length D. radiodurans RecJ (DrRecJ) protein was expressed and purified to further characterize its biochemical properties. DrRecJ possessed a Mn(2+) concentration-dependent nuclease activity where the optimal Mn(2+) concentration was 0.1mM. DrRecJ had a similar activity profile after adding 10mM Mg(2+) to reactions with different Mn(2+) concentrations, indicating that Mn(2+) is a RecJ regulator. Escherichia coli RecJ has no activity on 5' ssDNA tails shorter than 6-nt, but DrRecJ could effectively degrade DNA with a 4-nt 5' ssDNA tail, suggesting that DrRecJ may have a wider range of DNA substrates. Moreover, SSB in D. radiodurans stimulated the DrRecJ exonuclease activity, whereas DdrB inhibited it and provided protection to ssDNA. Overall, our results indicate that recJ is a nonessential gene in D. radiodurans and that the activity of DrRecJ is regulated by Mn(2+) and SSB-DdrB. PMID- 22301371 TI - Cognitive function in health and disease: the role of epigenetic mechanisms. AB - Epigenetic mechanisms regulate the interaction between the genome and the environment and have been implicated in the etiology of various brain diseases. One type of epigenetic modification, histone acetylation, is dynamically altered during memory formation. Histone acetylation is regulated by the activities of histone deacetylase (HDAC) and histone acetyltransferase enzymes. The use of HDAC inhibitors has emerged as a promising new strategy for the therapeutic intervention of neurodegenerative disease. We used a combination of pharmacological and mouse genetic approaches that allowed us to identify HDAC2 as a specific negative regulator of synaptic plasticity and memory formation. Our results suggest that HDAC inhibitors enhance cognitive function by inhibiting HDAC2, which renders HDAC2 target genes more accessible to transcriptional activators and coactivators recruited by neuronal activity stimulation. The data presented at the 2011 Barcelona ADPD Conference delineate a novel and important role for HDAC2 activity in the cognitive impairments associated with neurodegenerative disease. PMID- 22301372 TI - Assay performance improved, but which "scorecard" designation for Vitros Troponin I? AB - BACKGROUND: Since cardiac troponins assay technology should comply with the recommendations of scientific societies (i.e. imprecision (10%) at the 99th percentile value observed in healthy subjects being the analytical qualifying aspect), the aim of the present study was to evaluate whether an improved troponin assay (Vitros Troponin I ES) provides data that meet the "guideline acceptable"criteria recently defined in a proposed scorecard. METHODS: Vitros Troponin I ES, an enhanced chemiluminescence immunoassay, was evaluated in a multicenter study considering: limit of blank (LOB, 60 replicates of 0 calibrators), limit of detection (LOD, 12 measurements for each of 5 serum pools), precision, linearity using control materials and serum plasma pool; matrix samples study matching serum and lithium-heparin plasma (n=107 hospitalized patients); the 99th percentile limit in serum samples from 500 healthy Caucasian donors. RESULTS: LOB and LOD, 0.0029 MUg/L and 0.0030 MUg/L respectively; coefficients of variation (total CV%), obtained by running 3 levels of control materials and 10 serum pools, from 15.2% (x(-)=0.014 MUg/L) to 2.0% (x(-)=5.324 MUg/L); method, linear up to 70 MUg/L. No significant differences were found between serum and lithium-heparin matched sample (p=0.48) values; 99th percentile limit of cTnI distribution in healthy donors, 0.021 MUg/L. CONCLUSION: Since its analytical reliability meets the proposed performance and scorecard requirements, the Vitros TropI method can be considered "contemporary" and "guideline acceptable". PMID- 22301373 TI - Is serum anti-cyclic citrullinated peptide level useful in the diagnosis of rheumatoid arthritis? AB - BACKGROUND: To find out whether serum level of anti-cyclic citrullinated peptides (anti-CCP) could be useful in the diagnosis of rheumatoid arthritis (RA). METHODS: The study was performed against 1972 patients who visited Hanyang University Medical Center and were tested positive for anti-CCP. RESULTS: When test results were classified into 6 groups according to the anti-CCP level, diagnostic rates of RA in each group were distributed from 73.6% to 77.2%. The increase of serum level did not have any correlation with the diagnostic rate of RA. CONCLUSIONS: The level of serum anti-CCP was not useful in the diagnosis of RA. PMID- 22301374 TI - Interference in a glucose dehydrogenase-based glucose meter revisited. PMID- 22301375 TI - Laboratory screening of potential predators of the poultry red mite (Dermanyssus gallinae) and assessment of Hypoaspis miles performance under varying biotic and abiotic conditions. AB - The poultry red mite, Dermanyssus gallinae (De Geer), is the most important ectoparasitic pest of layer hens worldwide and difficult to control through 'conventional' synthetic acaricides. The present study aimed to identify a suitable predator of D. gallinae that could potentially form the basis of biological control in commercial poultry systems. From four selected predatory mite species (Hypoaspis miles (Berlese), Hypoaspis aculeifer (Canestrini), Amblyseius degenerans (Berlese) and Phytoseiulus persimilis (Athias-Henriot)), Hypoaspis mites demonstrated the greatest potential as predators of D. gallinae. Experiments were also conducted to assess the effect of environmental (temperature and dust), physical (presence of harbourages) and biological (presence of alternative prey) factors on the predatory efficacy of H. miles. Predation of D. gallinae per se was observed under all conditions tested, though was found to be temperature-dependent and reduced by the presence of alternative prey. PMID- 22301376 TI - Direct anthelmintic and immunostimulatory effects of oral dosing semi-purified phytohaemagglutinin lectin in sheep infected with Teladorsagia circumcincta and Trichostrongylus colubriformis. AB - Lectins are plant secondary compounds that can have anthelmintic properties in vitro. In particular, the phytohaemagglutinin lectin extracted from Phaseolus vulgaris has been shown to inhibit the feeding of Trichostrongylus colubriformis and Teladorsagia circumcincta L1 larvae. However, little is known about the potential anthelmintic properties of this lectin in vivo and its suitability to control gastrointestinal parasite infections in lambs. In a 2 * 2 study, lambs were either orally dosed, or not, with 2.3mg semi-purified PHA lectin per kg live weight (LW) per day, whilst concurrently infected, or not, with 1000 T. circumcincta and 1000 T. colubriformis L3 infective larvae per day for 42 days. There were no adverse clinical effects observed with this dose of PHA lectin. Although worm burdens were similar, animals dosed with PHA lectin had reduced concentration of nematode eggs in the faeces compared with their non-lectin dosed counterparts (P=0.026), suggesting that there may be a direct effect of PHA lectin on parasite fecundity. Irrespective of infection, PHA lectin had immune stimulatory properties with increased eosinophillia in both abomasal and small intestine tissue sections taken at slaughter on day 42 (P<0.02 for both) and a tendency for decreased ability of Teladorsagia larvae to penetrate abomasal tissue explants (P=0.06). Compared with infection alone, concurrent PHA lectin dosing and infection further increased the number of eosinophils (P<0.01), PAS positive (mucin-producing cells) (P=0.03) and tended to increase the number of T helper cells (P=0.06). No interactions were observed for cell populations in small intestine tissue sections. These results suggest PHA lectin could have two possible modes of action against T. circumcincta and T. colubriformis, a direct anthelmintic effect on nematode fecundity and an indirect effect through enhancing local immune responses in the host. PMID- 22301377 TI - Crossroads in the evaluation of paraoxonase 1 for protection against nerve agent and organophosphate toxicity. AB - Human paraoxonase 1 (PON1), a 45kDa arylesterase associated with circulating high density lipoproteins (HDL), has been described as an anti-atherogenic element in cardiovascular disorders. The efficacy of PON1 as a catalytic bioscavenger against OP and CWNA toxicity has been on debate for the last few decades. Hydrolysis of various organophosphates (OPs) and chemical warfare nerve agents (CWNAs) by PON1 has been demonstrated in both in vitro and in vivo experiments. Recently, we established the protective efficacy of human and rabbit serum purified PON1 as well as human recombinant PON1 expressed in Trichoplusia ni larvae against nerve agent toxicity in guinea pigs. Exogenous administration of purified PON1 was effective in protecting against 1.2 X LCt(50) of sarin and soman administered endotracheally with microinstillation technology. However, the short half-life of exogenously administered PON1, probably due to poor association with circulating HDL, warrant alternative approaches for successful utility of PON1 in the treatment of OP/CWNA toxicity. In this mini review, we address the pros and cons of current PON1 prophylaxis and propose potential solutions for successful development of PON1 as an effective catalytic bioscavenger. PMID- 22301378 TI - Quantitative analysis of GFAP- and S100 protein-immunopositive astrocytes to investigate the severity of traumatic brain injury. AB - Previous studies have shown that diffuse cortical astrocyte damage is seen in acute deaths due to brain injury and mechanical asphyxiation. The present study quantitatively investigated the number of astrocytes that showed GFAP- and S100 protein immunopositivity in the cerebral white matter and hippocampus at the sites distant from primary injury with regard to survival time, complication, and the immediate cause of death of brain injury cases. Autopsy cases of brain injury (8-48 h postmortem) comprising acute/subacute deaths (survival time, <3/6 h-3 days; n=27/42) and delayed deaths (survival time >3 days) with/without complications (n=30/22) were examined. Delayed death cases with complications were subdivided into those in which the immediate cause of death had been determined as cerebral dysfunction (n=22) and those that had been determined as due to fatal complications (n=8). For controls, natural deaths from pneumonias (n=12) and sudden cardiac deaths (n=27) were used. In brain injury cases, the numbers of astrocytes in the cerebral white matter and hippocampal CA4 region were significantly lower for subacute death and delayed death without complications (p<0.05-0.001). Delayed death with fatal complications showed a significant increase in the number of astrocytes (p<0.05). Among delayed death cases, the numbers of astrocytes were higher in the cases with fatal complications than in those without complications and with non-fatal complications, although the latter cases showed large variations in the numbers of these astrocytes. These findings suggest that critical brain injury causes acute death without evident astrocyte pathology and that subacute death is associated with progressive brain damage accompanied by an astrocyte loss. In delayed death cases, the numbers astrocytes might be closely related to the severity of posttraumatic brain injury. GFAP and S100-immunopositivity might be useful for elucidating the cause and process of deaths due to brain injury. PMID- 22301379 TI - Airway obstruction lability helps distinguish levels of disease activity in asthma. AB - Classifying disease activity in asthma relies on clinical and physiological variables, but these variables do not capture all aspects of asthma that distinguish levels of disease activity. We used data from two pivotal trials of montelukast in asthma to classify disease activity as "high" or "low". We performed a principal component analysis (PCA) of disease activity using 21 efficacy outcome variables, including several novel derived outcome variables reflecting clinical and airway obstruction lability. Then we performed discriminant analysis (DA) based on disease activity classification. PCA revealed 6 factors (daytime asthma control, nighttime-predominant asthma control, airway obstruction, exacerbations, clinical lability, airway obstruction lability) that explained 76% of the variance between outcome variables. Although airway obstruction lability (comprising both diurnal variability in peak expiratory flow and diurnal variability in beta-agonist use) accounted for only 6% of the explained variance in PCA, in DA it was more accurate (canonical coefficient 0.75) than traditional measures of asthma severity such as obstruction (-0.54) and daytime control (-0.56) in distinguishing between high and low disease activity. We conclude that airway obstruction lability, a parameter not typically captured in clinical trials, may contribute to more complete assessment of asthma disease activity and may define an emerging clinical target of future therapy. PMID- 22301380 TI - Evaluation of hepatic structures by transesophageal echocardiography. PMID- 22301381 TI - Acute-onset dyspnea and superior vena cava syndrome during dialysis. PMID- 22301382 TI - Suppression of the cough reflex by inhibition of ERK1/2 activation in the caudal nucleus tractus solitarii of the rabbit. AB - The caudal nucleus tractus solitarii (cNTS), the predominant site of termination of cough-related afferents, has been shown to be a site of action of some centrally acting antitussive agents. A role of ERK1/2 has been suggested in acute central processing of nociceptive inputs. Because pain and cough share similar features, we investigated whether ERK1/2 activation could also be involved in the central transduction of tussive inputs. For this purpose, we undertook the present research on pentobarbital sodium-anesthetized, spontaneously breathing rabbits by using microinjections (30-50 nl) of an inhibitor of ERK1/2 activation (U0126) into the cNTS. Bilateral microinjections of 25 mM U0126 caused rapid and reversible reductions in the cough responses induced by both mechanical and chemical (citric acid) stimulation of the tracheobronchial tree. In particular, the cough number and peak abdominal activity decreased. Bilateral microinjections of 50 mM U0126 completely suppressed the cough reflex without affecting the Breuer-Hering inflation reflex, the pulmonary chemoreflex, and the sneeze reflex. These U0126-induced effects were, to a large extent, reversible. Bilateral microinjections of 50 mM U0124, the inactive analog of U0126, at the same cNTS sites had no effect. This is the first study that provides evidence that ERK1/2 activation within the cNTS is required for the mediation of cough reflex responses in the anesthetized rabbit. These results suggest a role for ERK1/2 in the observed effects via nontranscriptional mechanisms, given the short time involved. They also may provide hints for the development of novel antitussive strategies. PMID- 22301383 TI - Probiotic and postbiotic activity in health and disease: comparison on a novel polarised ex-vivo organ culture model. AB - BACKGROUND AND AIMS: Probiotics and their metabolic products, here called postbiotics, have been proposed as food supplements for a healthier intestinal homeostasis, but also as therapeutic aids in inflammatory bowel disease (IBD) with, however, very little clinical benefit. This may be due to the lack of reliable preclinical models for testing the efficacy of different strains. METHODS: The activity of three probiotic strains of Lactobacillus (or a postbiotic) was analysed and compared with a pathogenic strain of Salmonella on a novel organ culture system of human healthy and IBD intestinal mucosa developed in our laboratory. The system maintains an apical to basolateral polarity during stimulation due to the presence of a glued cave cylinder. The cylinder is detached at the end of the experiment and the tissue is processed for histology and immunohistochemistry. Cytokines released from the basolateral side are analysed. RESULTS: The model system provides several physiological characteristics typical of a mucosal microenvironment including the presence of an organised mucus layer and an apical to basolateral polarity. Polarised administration of bacteria is critical to control the ensuing immune response as it mimics the physiological entrance of bacteria. The authors show that probiotics are not always beneficial for the healthy host and can also be detrimental in inflamed IBD. This study shows that a potent postbiotic can protect against the inflammatory properties of invasive Salmonella on healthy tissue and also downregulate ongoing inflammatory processes in IBD tissue. CONCLUSIONS: Probiotics can have inflammatory activities in both healthy and IBD tissue. Valid preclinical data on proper model systems should therefore be obtained before specific probiotic strains enter the clinics, especially if administered during acute inflammatory responses. Postbiotics may be a safe alternative for the treatment of patients with IBD in the acute inflammatory phase. PMID- 22301384 TI - A R2R3-type MYB gene, OsMYB2, is involved in salt, cold, and dehydration tolerance in rice. AB - MYB-type transcription factors play a diverse role in plant development and response to abiotic stress. This study isolated a rice R2R3-type MYB gene, OsMYB2, and functionally characterized its role in tolerance to abiotic stress by generating transgenic rice plants with overexpressing and RNA interference OsMYB2. Expression of OsMYB2 was up-regulated by salt, cold, and dehydration stress. OsMYB2 was localized in the nucleus with transactivation activity. No difference in growth and development between the OsMYB2-overexpressing and wild type plants was observed under normal growth conditions, but the OsMYB2 overexpressing plants were more tolerant to salt, cold, and dehydration stresses and more sensitive to abscisic acid than wild-type plants. The OsMYB2 overexpressing plants accumulated greater amounts of soluble sugars and proline than wild-type plants under salt stress. Overexpression of OsMYB2 enhanced up regulation of genes encoding proline synthase and transporters. The OsMYB2 overexpressing plants accumulated less amounts of H(2)O(2) and malondialdehyde. The enhanced activities of antioxidant enzymes, including peroxidase, superoxide dismutase, and catalase, may underlie the lower H(2)O(2) contents in OsMYB2 overexpressing plants. There was greater up-regulation of stress-related genes, including OsLEA3, OsRab16A, and OsDREB2A, in the OsMYB2-overexpressing plants. Microarray analysis showed that expression of numerous genes involving diverse functions in stress response was altered in the OsMYB2-overexpressing plants. These findings suggest that OsMYB2 encodes a stress-responsive MYB transcription factor that plays a regulatory role in tolerance of rice to salt, cold, and dehydration stress. PMID- 22301385 TI - Review of cerebral microangiopathy and Alzheimer's disease: relation between white matter hyperintensities and microbleeds. AB - Although Alzheimer's disease (AD) is basically considered to be a neurodegenerative disorder, cerebrovascular disease is also involved. The role of vascular risk factors and vascular disease in the progression of AD remains incompletely understood. With the development of brain MRI, it is now possible to detect small-vessel disease, whose prevalence and severity increase with age. The first types of small-vessel disease to be described were white matter hyperintensities (WMHs). More recently, small areas of signal loss on T(2)* weighted images, also called microbleeds (MBs), have been reported. Cerebral MBs are focal deposits of hemosiderin that indicate prior microhemorrhages around small vessels, related to either ruptured atherosclerotic microvessels or amyloid angiopathy. Consequently, using brain MRI for the detection of microangiopathy may prove useful to improve our understanding of the impact of the vascular burden in AD pathology. The relationship between microangiopathy and the clinical course of AD or the conversion of mild cognitive impairment to AD remains questionable in terms of cognitive or affective symptoms, particularly if we consider MBs. PMID- 22301386 TI - Changes of learning and memory in aged rats after isoflurane inhalational anaesthesia correlated with hippocampal acetylcholine level. AB - BACKGROUND AND PURPOSE: It has not been clearly described for mechanisms of postoperative cognitive dysfunction (POCD), but not yet for narcotic in connection with POCD. Acetylcholine plays important roles in learning and memory especially in elderly people. It is not very clear that cholinergic changes in the hippocampus are in relation to spatial memory impairment. The effects of isoflurane, a commonly used inhalation anaesthetic, as well as acetylcholine on learning and memory in the brain tissue of aged rats were observed in present study. We investigated the inhalation anaesthesia drug's effect on cholinergic system to examine whether the regional and progressive cholinergic changes may lead to POCD. METHODS: Seventeen-month-old rats were randomly assigned to either an isoflurane anaesthesia group (n=17) or propofol anaesthesia group (n=17). In isoflurane anaesthesia experiment group, isoflurane (1.4 to 1.7% for 2 hours) was delivered via a ventilator to make freely moving microdialysis model. In propofol group, propofol was administered by continuous infusion via a tail vein catheter to make freely moving microdialysis model. They were all mechanically ventilated. Morris Water Maze test was used to assess the learning and memory abilities of all the two groups' rats twice a day for 5 days. Microdialysis was performed on the freely moving rats to determine the levels of acetylcholine in the brain tissues immediately after each Water Maze test. RESULTS: The isoflurane anaesthesia treatment increased the escape latency contrast to propofol anaesthesia group. The isoflurane anaesthesia's rats were then divided into isoflurane-induced severe learning/memory impairment group (n=6, mean escape latency is 1.96 times more than that of in propofol anaesthesia group) and the isoflurane-induced mild learning/memory impairment group (n=11, mean escape latency is equal or less than 1.96 times of that in propofol anaesthesia group). The results demonstrated that those rats that were categorized in the isoflurane induced severe learning/memory impairment group had decreased levels of acetylcholine in the brain tissue as compared to those rats categorized in the mild learning/memory impairment group and in propofol anaesthesia group. CONCLUSION: The results indicated that isoflurane may impair learning and memory in aged rats. PMID- 22301387 TI - Global stability of plasma proteomes for mass spectrometry-based analyses. AB - Peptide-based mass spectrometry approaches, such as multiple reaction monitoring, provide a powerful means to measure candidate protein biomarkers in plasma. A potential confounding problem is the effect of preanalytical variables, which may affect the integrity of proteins and peptides. Although some blood proteins undergo rapid physiological proteolysis ex vivo, the stability of most plasma proteins to preanalytical variables remains largely unexplored. We applied liquid chromatography-tandem mass spectrometry shotgun proteomics and multiple reaction monitoring analyses to characterize the stability of proteins at the peptide level in plasma. We systematically evaluated the effects of delay in plasma preparation at different temperatures, multiple freeze-thaw cycles and erythocyte hemolysis on peptide and protein inventories in prospectively collected human plasma. Time course studies indicated few significant changes in peptide and protein identifications, semitryptic peptides and methionine-oxidized peptides in plasma from blood collected in EDTA plasma tubes and stored for up to a week at 4 degrees C or room temperature prior to plasma isolation. Similarly, few significant changes were observed in similar analyses of plasma subjected to up to 25 freeze-thaw cycles. Hemolyzed samples produced no significant differences beyond the presence of hemoglobin proteins. Finally, paired comparisons of plasma and serum samples prepared from the same patients also yielded few significant differences, except for the depletion of fibrinogen in serum. Blood proteins thus are broadly stable to preanalytical variables when analyzed at the peptide level. Collection protocols to generate plasma for multiple reaction monitoring-based analyses may have different requirements than for other analyses directed at intact proteins. PMID- 22301388 TI - Analysis of high accuracy, quantitative proteomics data in the MaxQB database. AB - MS-based proteomics generates rapidly increasing amounts of precise and quantitative information. Analysis of individual proteomic experiments has made great strides, but the crucial ability to compare and store information across different proteome measurements still presents many challenges. For example, it has been difficult to avoid contamination of databases with low quality peptide identifications, to control for the inflation in false positive identifications when combining data sets, and to integrate quantitative data. Although, for example, the contamination with low quality identifications has been addressed by joint analysis of deposited raw data in some public repositories, we reasoned that there should be a role for a database specifically designed for high resolution and quantitative data. Here we describe a novel database termed MaxQB that stores and displays collections of large proteomics projects and allows joint analysis and comparison. We demonstrate the analysis tools of MaxQB using proteome data of 11 different human cell lines and 28 mouse tissues. The database wide false discovery rate is controlled by adjusting the project specific cutoff scores for the combined data sets. The 11 cell line proteomes together identify proteins expressed from more than half of all human genes. For each protein of interest, expression levels estimated by label-free quantification can be visualized across the cell lines. Similarly, the expression rank order and estimated amount of each protein within each proteome are plotted. We used MaxQB to calculate the signal reproducibility of the detected peptides for the same proteins across different proteomes. Spearman rank correlation between peptide intensity and detection probability of identified proteins was greater than 0.8 for 64% of the proteome, whereas a minority of proteins have negative correlation. This information can be used to pinpoint false protein identifications, independently of peptide database scores. The information contained in MaxQB, including high resolution fragment spectra, is accessible to the community via a user-friendly web interface at http://www.biochem.mpg.de/maxqb. PMID- 22301389 TI - Multiclass primary antiretroviral drug resistance in a patient presenting HIV-1/2 dual infection. PMID- 22301390 TI - Periodontal disease-associated compensatory expression of osteoprotegerin is lost in type 1 diabetes mellitus and correlates with alveolar bone destruction by regulating osteoclastogenesis. AB - Alveolar bone resorption results from the inflammatory response to periodontal pathogens. Systemic diseases that affect the host response, such as type 1 diabetes mellitus (DM1), can potentiate the severity of periodontal disease (PD) and accelerate bone resorption. However, the biological mechanisms by which DM1 modulates PD are not fully understood. The aim of this study was to determine the influence of DM1 on alveolar bone resorption and to evaluate the role of receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin (OPG) in osteoclastogenesis in rats. PD was induced by means of ligature in nondiabetic and in streptozotocyn-induced DM1 rats. Morphological and morphometric analyses, stereology and osteoclast counting were performed. RANKL and OPG mRNA levels, protein content, and location were determined. PD caused alveolar bone resorption, increased the number of osteoclasts in the alveolar bone crest and also promoted changes in RANKL/OPG mRNA expression. DM1 alone showed alveolar bone destruction and an increased number of osteoclasts at the periapical and furcal regions. DM1 exacerbated these characteristics, with a greater impact on bone structure, resulting in a low OPG content and a higher RANKL/OPG ratio, which correlated with prominent osteoclastogenesis. This work demonstrates that the effects of PD and DM1 enhance bone destruction, confirms the importance of the RANKL signaling pathway in bone destruction in DM1 in animal models and suggests the existence of alternative mechanisms potentiating bone degradation in PD. PMID- 22301391 TI - The association of rate pressure product (RPP) and myocardial perfusion imaging (MPI) findings: a preliminary study. AB - INTRODUCTION: The product of heart rate and systolic blood pressure, termed as rate-pressure product (RPP), is a very reliable indicator of myocardial oxygen demand and is widely used clinically. There have been previous attempts to describe the relationship between RPP and the onset of pain in angina pectoris. The current study aimed to evaluate the association between RPP results and scan findings. MATERIALS AND METHODS: In total, 497 patients with suspected coronary artery disease (CAD) underwent gated, single-photon emission computed tomography (SPECT) imaging with dipyridamole, exercise, or dobutamine stress, and were included in this study. Baseline and maximum heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and electrocardiogram (ECG) results were recorded. The rate-pressure product (RPP) was calculated as the product of heart rate and systolic arterial pressure for both baseline and maximum measures. The difference between the RPP max and the basal RPP is known as the RPP reserve. Researchers also obtained semi-quantitative analyses of myocardial perfusion imaging (MPI), using gated software, demographic information, risk factors of CAD, and pretest likelihoods of CAD using nomograms. RESULT: Four hundred and ninety-seven cases, including 426 patients with dipyridamole stress, 59 with exercise stress, and 12 with dobutamine stress, underwent myocardial perfusion imaging. Scan results were positive in 194 (45.5%) and negative in 232 (54.5%) patients with dipyridamole stress. In patients with exercise stress, the scan was positive in 24 (40.7%) cases and negative in 35 (59.3%) cases. In dobutamine stressed patients, the scan was positive in 6 (50%) cases and negative in the 6 remaining cases. Dipyridamole stress resulted in a significant difference between HR at rest and at maximum (28.95 +/- 24.53, p value<0.0001), between systolic BP at rest and maximum (6.75 +/- 12.50, p value<0.0001) and between diastolic BP at rest and maximum (1.45 +/- 5.80; p value<0.0001). There was a significant correlation between sum stress scores (SSS) and reserved RPP (r= -0.12, p-value<0.001) which, in dipyridamole patients, was r=-0.18, p-value=0.0001). In addition, there was a significant association between reserved RPP and risk of CAD (p-value<0.001). In the patients with dipyridamole stress, the ejection fraction (EF) change (odds ratio =0.92; 95% CI: 0.86-0.98; p=0.01), reserve RPP (odds ratio =1.00; 95% CI: 1.00-1.00; p=0.04), risk of CAD (odds ratio =5.80; 95% CI: 3.21-10.50; p<0.0001) and age (odds ratio =0.94; 95% CI: 0.89-0.98; p=0.01) were associated significantly with MPI results, using multiple logistic regressions. CONCLUSION: The study demonstrated that RPP is associated with MPI findings using gated SPECT imaging with dipyridamole stress. However, to confirm this preliminary result, further studies are mandatory. PMID- 22301392 TI - Anticoagulation monitoring during extracorporeal circulation with the Hepcon/HMS device. AB - OBJECTIVE: The objective of our study was to compare the standard protocol of anticoagulation to the Hepcon/HMS. METHOD: This study included forty-four patients who underwent coronary bypass grafting surgery (CABG), or biological aortic valve replacement (AVR). Unfractionated heparin (UH) was used for patients who underwent operations in the control group (n = 22) (300U/Kg of UH with a goal of an ACT of 400s). The heparin was antagonized dose/dose by protamine. For the patients who underwent operations in the HMS group (n = 22), the heparin and protamine doses were assessed by the Hepcon/HMS device. RESULTS: The sex ratio amounted to 1.93 (29 men and 15 women) and the mean age was 70 +/- 11 years. The patients in the HMS group had a chest closure time that was significantly shorter than patients in the control group. The times were, respectively, 42 +/- 15 minutes and 68 +/- 27 minutes (p = 0.001). The protamine/heparin ratio was significantly lower in the HMS group (0.62 +/- 0.13 vs. 1 +/- 0.11) (p = 0.0001). The postoperative bleeding amounted to 804 +/- 729 ml in the HMS group versus 1416 +/- 1103 in the control group (p = 0.016). In multivariate linear regression analysis, only two independent factors were significantly associated with bleeding: the Hepcon/HMS (OR = 0.1-p = 0.03) and the preoperative hemoglobin rate (OR = 1.4 - p = 0.05). Postoperatively, within 72 hours, the red blood cell transfusion was 1.04 +/- 1.5 units for the HMS group and 2.1 +/- 1.87 units for the control group (p = 0.05). CONCLUSION: During cardiac surgery under CPB, heparin and protamine titration with the Hepcon/HMS device could predict a lower protamine dose and lower postoperative bleeding without higher thromboembolic events, and lower perioperative red blood cell transfusion with a shorter chest closure time. PMID- 22301393 TI - Eosinophilia during psoriasis treatment with TNF antagonists. PMID- 22301394 TI - Camptothecin fails to induce apoptosis in tumor necrosis factor-alpha-treated HaCaT cells. AB - Camptothecin (CPT), a DNA topoisomerase I inhibitor, was originally isolated from the fruits of the Chinese Camptotheca acuminata tree. CPT and its derivatives have been used in the treatment of psoriasis and cancer in China for decades. It is well known that tumor necrosis factor-alpha (TNF-alpha) is a key proinflammatory cytokine in the pathogenesis of psoriasis. In this study, we investigated the effect of CPT on TNF-alpha-treated HaCaT cells. The results indicated that CPT in the concentration range of 0.5-2.0 MUg.ml(-1) failed to show any proapoptotic effect in HaCaT cells. It was found that both CPT and TNF alpha up-regulated the expression of TRAIL receptor 1/2 but not TRAIL in HaCaT cells. Furthermore, the expression of antiapoptotic proteins (IAP1, IAP2, and Bcl X(L)) was up-regulated by TNF-alpha and suppressed by CPT in HaCaT cells. Because these gene products are known to be regulated by nuclear factor-kappa B (NF kappaB), we examined the role of CPT on NF-kappaB activation. It was found that CPT not only failed to inhibit TNF-alpha-induced NF-kappaB activation but also contributed to NF-kappaB activation. In addition to these effects, CPT also promoted the production of interleukin-6, similar to TNF-alpha, in HaCaT cells. In conclusion, despite ample evidence supporting CPT-induced carcinoma cell apoptosis, our study clearly shows that CPT fails to show any proapoptotic effects in HaCaT cells, even though it enhanced TRAIL receptor 1/2 expression and inhibited the expression of TNF-alpha-induced antiapoptotic proteins. Taken together, this study demonstrates that CPT fails to block the activity of TNF alpha. With respect to the NF-kappaB-activating role of CPT, we suggest that the benefit of CPT in the treatment of psoriasis should be reevaluated. PMID- 22301395 TI - Neoadjuvant endocrine therapy: for whom, for how long? PMID- 22301396 TI - Nanoparticle delivery systems for cancer therapy: advances in clinical and preclinical research. AB - Conventional anticancer drugs display significant shortcomings which limit their use in cancer therapy. For this reason, important progress has been achieved in the field of nanotechnology to solve these problems and offer a promising and effective alternative for cancer treatment. Nanoparticle drug delivery systems exploit the abnormal characteristics of tumour tissues to selectively target their payloads to cancer cells, either by passive, active or triggered targeting. Additionally, nanoparticles can be easily tuned to improve their properties, thereby increasing the therapeutic index of the drug. Liposomes, polymeric nanoparticles, polymeric micelles and polymer- or lipid-drug conjugate nanoparticles incorporating cytotoxic therapeutics have been developed; some of them are already on the market and others are under clinical and preclinical research. However, there is still much research to be done to be able to defeat the limitations of traditional anticancer therapy. This review focuses on the potential of nanoparticle delivery systems in cancer treatment and the current advances achieved. PMID- 22301397 TI - Tyrosine kinase inhibitors and drug interactions: a review with practical recommendations. AB - The adverse effects associated to traditional chemotherapy are well known and broadly studied. In the recent years several tyrosine kinase inhibitors have been approved for cancer treatment and numerous are under investigation. These drugs target specific mutated/overexpressed tyrosin kinase receptors and frecuently their pharmacokinetic/pharmacodinamic behavior is not fully elucidated. These new drugs may interact with non-antineoplastic drugs leading to undesirable adverse effects. In this article, we will discuss different types of drug interactions and briefly review the pharmacokinetics and mechanisms of action of tyrosine kinase inhibitors in clinical use, with a particular emphasis on the risk of the occurrence of such interactions based on currently available scientific evidence. PMID- 22301398 TI - Review of Chinese clinical trials on CIK cell treatment for malignancies. AB - China is the country where the most clinical trials on CIK cells have been performed. We aimed to provide definite evidence for using CIK cell treatment and extrapolate a common applicative standard for malignancies. We chose the VIP database of Chinese scientific and technological journals to search the literature. We entered the keywords "CIK" or "xi bao yin zi you dao de sha shang xi bao" (the equivalent Chinese phrase for CIK cells, by Chinese characters) and searched for in vivo human trials. In 24 collected trials, 936 patients were treated with CIK cells, 525 men and 246 women. The cultivation time of CIK cells ranged from 7 to 28 days. In five studies, CIK cells were co-cultured with dendritic cells. The total number of CIK cells used ranged from 6*10(6) to 1.5*10(10). The total number of DC-CIK cells used ranged from 1*10(9) to 1.3*10(10). In all studies, those immune parameters and tumour markers examined increased, but not all increased significantly. Of the reported 563 patients, 40 had a complete response, 126 had a partial response, 125 had a minimal response, 135 had stable disease and 58 had progressive disease. The remaining 76 patients did not reach an objective response. The total response rate was 51.7% (291/563). The toxicities were slight. CIK cell treatment is a promising and safe modality for treating malignancies. We proposed a standard for cultivating CIK cells. PMID- 22301399 TI - Ten-year results of a phase II study with a single fraction of high-dose-rate brachytherapy (FAST-boost) after whole breast irradiation in invasive breast carcinoma. AB - PURPOSE: We present the results of a prospective ten-year follow-up study to prove the effectiveness of a single fraction of 192-Ir high-dose-rate (HDR) brachytherapy (BT) as a boost. PATIENTS AND METHODS: Between 1999 and 2000, 84 consecutive patients with invasive breast carcinoma, with over 4 mm free margins after conservative surgery, were treated. All cases were stages T1-2, except for one case, a stage T3, 81% pN0, 19% pN1-2. Chemotherapy was used in 47% and hormonal therapy in 87%. Whole breast external beam radiotherapy (46 Gy) was followed 1-2 weeks later by an implant with metallic needles. A 7 Gy single dose of HDR BT to the 90% isodose line was delivered on an outpatient basis. Dosimetry was performed theoretically. This technique is called FAST-boost because the whole treatment is delivered in about two hours. RESULTS: With a median follow-up of 120 months, three patients relapsed in the margin of the implant and two in a different quadrant (5/84, 6%). Actuarial local control at five and ten years was 98.5% and 95.6%. Overall survival was 92.7% and 90.2%, and disease-free survival 90.2% and 79.9%. Cosmetic results were good or excellent in 92.5%. CONCLUSIONS: A single-fraction HDR boost with rigid needles (FAST-boost) is a good, quick, simple technique when surgical margins are free. PMID- 22301400 TI - Association of increased DNA methyltransferase expression with carcinogenesis and poor prognosis in pancreatic ductal adenocarcinoma. AB - INTRODUCTION: Epigenetic modifications play an important role in multistage carcinogenesis. The role of the three functional DNA methyltransferases (DNMTs) in pancreatic carcinogenesis has not been fully understood. The main goal of this study was to examine DNMT expression in different stages of pancreatic ductal adenocarcinoma (PDAC), and evaluate their prognostic significance in PDAC. MATERIALS AND METHODS: A large number of premalignant and malignant pancreatic lesions were obtained by manual microdissection. Quantitative real-time RT-PCR was used to detect DNMTs mRNA expression. Nonparametric test, logrank test and Cox regression analysis were used to evaluate the clinical significance of DNMT expression. RESULTS: The mRNA expression of the three DNMTs increased with the development of pancreatic cancer from normal duct to pancreatic intraductal neoplasia and further to PDAC, and were statistically correlated with each other. Expression of the three DNMTs was statistically correlated with TNM staging and history of chronic pancreatitis. DNMT3A and DNMT3B, but not DNMT1 expression, was statistically correlated with tumour size. Patients with higher levels of DNMT1, DNMT3A and/or DNMT3B expression had an overall lower survival than those with lower levels of expression. Univariate analysis showed that high expression levels of DNMTs, alcohol consumption, tumour differentiation and TNM staging were statistically significant risk factors. Multivariate analysis showed that high level of DNMT3B expression and tumour differentiation were statistically significant independent poor prognostic factors. CONCLUSIONS: These results suggested that pancreatic carcinogenesis involves an increased mRNA expression of three DNMTs, and they may become valuable diagnostic and prognostic markers as well as potential therapeutic targets for pancreatic cancer. PMID- 22301401 TI - Phase II trial with letrozole to maximum response as primary systemic therapy in postmenopausal patients with ER/PgR[+] operable breast cancer. AB - PURPOSE: Letrozole is superior to tamoxifen in terms of response and breast preservation rates as primary systemic therapy (PST) in postmenopausal women with ER-positive early breast cancer. However, the optimum duration of endocrine PST remains uncertain. METHODS: A phase 2 multicentre, open-label trial was conducted to evaluate the efficacy of letrozole over a preoperative period of 4 months to 1 year. Seventy postmenopausal patients (over 65 years) were recruited in four centers. The primary endpoint was to establish the optimal duration of treatment defined as the time required to attain the maximum response by clinical palpation. RESULTS: The median age of the group was 79 years (66-91) and the median tumour size 35 mm (range 25-100 mm). No severe adverse events were reported. Fifty-six patients were evaluable for the primary objective. A total of 43 patients (76.8%) achieved an objective response; 29 (51.8%) being partial and 14 (25.0%) complete. The median time to objective response was 3.9 months (95% CI, 3.3-4.5) and the median time to maximum response was 4.2 months (95% CI, 4.0 4.5), although 20 (37.1%) patients achieved the maximal response within 6-12 months. CONCLUSIONS: Letrozole shows a high activity and excellent tolerability as neoadjuvant therapy in elderly patients with endocrine-dependent breast cancer. Four to six months of letrozole as PST is an optimum duration with modest benefits thereafter. PMID- 22301402 TI - Interobserver variability in target volume delineation in postoperative radiochemotherapy for gastric cancer. A pilot prospective study. AB - INTRODUCTION: The aim of this study is to determine the interobserver variability (IV) between radiation oncologists (RO) in target volume delineation for postoperative gastric cancer (GC) radiotherapy planning. MATERIALS AND METHODS: Four physicians were asked to delimitate clinical target volume (CTV) on the same 3D CT images in 9 postoperative radiochemotherapy GC patients. Instructions were given to include tumour bed, remaining stomach, anastomosis, duodenal loop and local lymph nodes. The principal variable was spatial volume discrepancy between the main observer (called "A") and other observers (all called "B"), which were compared using the mathematical formula A?B/A?B, applied to the 3D CT images using Boolean operators. Analysis of variance with two random effects (observers and patients) was performed. RESULTS: Mean volumes were 1410 cm(3) for OBA, 1231 cm(3) for OB2, 734.6 cm(3) for OB3 and 1350 cm(3) for OB4. Discrepancies were 519.9+/-431.6 cm(3) for OB2, 652.1+/-294.36 cm(3) for OB3 and 225.90+/-237.07 cm(3) for OB4. Standard deviation ascribed to patients as random effect was 898.6 cm(3) and that ascribed to observers was 198.10 cm(3), considered as a statistically significant difference. CONCLUSIONS: A significant IV in target delineation that can be attributed to many factors depends more on patients' characteristics than RO delineating decisions. PMID- 22301403 TI - Examination of Smad2 and Smad4 copy-number variations in skin cancers. AB - BACKGROUND: Smad2 and Smad4 transcription factors were identified as the signalling mediators of transforming growth factor Beta (TGF Beta) pathway. Copy number variations (CNVs) have been discovered to have phenotypic consequences and be associated with various types of cancers. CNVs of Smad2 and Smad4 were found to be associated with cancer pathogenesis in the recent array-based study. However, no such study has been performed in skin cancer yet. In this study, we aim to examine the CNVs of Smad2 and Smad4 in skin samples. METHODS: A total of 195 paired samples including basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and actinic keratosis (AK) were included. Real-time PCR was used for the quantification of Smad2 and Smad4 copy numbers. RESULTS: CNVs of Smad2 showed statistical differences between cancer samples (both SCC and BCC) and normal tissues (p<0.05). For Smad4, statistical difference was observed only in SCC samples (p=0.014), but not in BCC and AK samples (p=0.173 and 0.314, respectively). Association analysis showed that the frequencies of Smad2 and Smad4 CNVs were correlated with the severity of skin abnormalities (p=0.002 for Smad2 and p=0.029 for Smad4). CONCLUSIONS: CNVs of Smad2 are associated with SCC and BCC, while CNVs of Smad4 are associated with SCC but not BCC. PMID- 22301404 TI - JAK/STAT signal pathway activation promotes progression and survival of human oesophageal squamous cell carcinoma. AB - OBJECTIVE: Inappropriate activation of JAK/STAT pathway occurs with high frequency in human cancers and is associated with cancer cell survival and proliferation. However, its role in oesophageal squamous cell carcinoma (ESCC) is unknown. METHODS: By immunohistochemistry, we analysed the expression of two components of this pathway, phosphorylated JAK-1 (pJAK-1) and phosphorylated STAT 3 (pSTAT-3), in 100 ESCC tumours and paired non-neoplastic oesophageal epithelia. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients. RESULTS: We found that pJAK-1 and pSTAT-3 expression was not detectable in normal oesophageal squamous cells. Primary ESCC with pJAK-1 positive and pSTAT-3-positive expression was detected in the cancer cell nests of 78 and 72 cases, respectively. In addition, the Pearson's correlation coefficient between pJAK-1 and pSTAT-3 expression was 0.806 (p<0.001). Moreover, pJAK-1 and pSTAT-3 expression was correlated with N stage (lymph node metastasis, both p=0.01), pTNM stage (p=0.008 and 0.009, respectively) and metastatic status (both p=0.01). Furthermore, pJAK-1 and pSTAT-3 expression was associated with shorter overall survival (both p<0.001) and shorter disease-free survival (p=0.005 and 0.006, respectively). By multivariate analysis, TNM clinical classification (T, p<0.001; N, p=0.002; M, p=0.02), pJAK-1 (p=0.002) and pSTAT-3 (p=0.003) were independent prognosis predictors of ESCC. CONCLUSION: These results provide convincing evidence for the first time that the JAK/STAT pathway may participate in the progress of ESCC. PMID- 22301405 TI - Circulating tumour cells in prostate cancer patients receiving salvage radiotherapy. AB - INTRODUCTION: Within 10 years of radical prostatectomy (RP), up to 30% of prostate cancer (PCa) patients will have a rise in prostate-specific antigen (PSA), requiring radiation therapy (RT). However, with current technology, distinction between local and distant recurrent PCa is not possible. This lack of an accurate test constrains the decision whether to offer systemic or local treatment. We hypothesise tests for detecting circulating tumour cells (CTCs) within the blood may assist with clinical decision-making and in this pilot study we investigated whether CTCs could be detected in this patient population using the CellSearch(r) system. MATERIALS AND METHODS: Blood samples were collected from PCa patients (n=26) prior to RT and 3 months following completion of RT. Samples were analysed for PSA level via immunoassay and CTC number using the CellSearch(r) system. RESULTS: CTCs could be detected in this patient population and following RT CTCs appeared to decrease. However, no association was observed between a higher PSA and an increased number of CTCs pre- or post-RT. Interestingly, patients who failed RT trended toward an increased/ unchanged number of CTCs following RT vs. a decreased number in patients with RT response. CONCLUSIONS: Our results demonstrate that CTCs can be detected in early-stage PCa and suggest the possibility that post-treatment reduction in CTC levels may be indicative of RT response . We are currently evaluating CTCs in a larger cohort of patients to validate our preliminary findings and further investigate the prognostic value of CTCs in this patient population. PMID- 22301406 TI - CYP2D6*4 allele and breast cancer risk: is there any association? AB - BACKGROUND: CYP2D6 is an important cytochrome P450 enzyme. These enzymes catalyse the oxidative biotransformation of about 25% of clinically important drugs as well as the metabolism of numerous environmental chemical carcinogens. The most frequent null allele of CYP2D6 in European populations, CYP2D6*4, has been studied here in order to elucidate whether a relationship exists between this allele and the risk of developing breast cancer in a Spanish population. MATERIALS AND METHODS: Ninety-six breast cancer Spanish patients and one hundred healthy female volunteers were genotyped for the CYP2D6*4 allele using AmpliChip CYP450 Test technology. RESULTS: Homozygous CYP2D6*4 frequency was significant lower in breast cancer patients than in the control group (OR=0.22, p=0.04). The heterozygous CYP2D6*4 group also displayed lower values in patients than in controls but the difference was not significant (OR=0.698, p=0.28). Therefore, the presence of the CYP2D6*4 allele seems to decrease susceptibility to breast carcinoma in the selected population. CONCLUSIONS: A possible decreased transformation of procarcinogens by CYP2D6*4 poor metabolisers could result in a protective effect against carcinogens. PMID- 22301407 TI - Spanish Society of Medical Oncology (SEOM) Cancer and Thrombosis Working Group. PMID- 22301408 TI - Preattentive processing of feared stimuli in blood-injection-injury fearful subjects. AB - This research aimed to study the defence responses of blood-injection-injury (BII) fearful subjects elicited by the preattentive processing of their feared objects and by an abrupt acoustic stimulus. We selected 21 BII fearful subjects and 25 non-fearful controls from an initial sample of 128 women, according to their scores on the Fear Survey Scale (damage subscale) and the Mutilation Questionnaire. Subjects were exposed to a burst of white noise to promote a defence response, and to 48 pictures, depicting mutilations, as well as other affective contents, displayed through a backward masking procedure. Heart rate (HR), skin conductance response (SCR) and corrugator supercilii activity were continuously recorded throughout the task. Both groups showed similar SCRs, EMG activity and cardiac defence responses to the acoustic stimulus, though fearful subjects showed greater initial HR deceleration than controls. While BII fearful subjects displayed the usual defence response when exposed to a non-feared threatening stimulus, the preattentive processing of the pictures did not reveal autonomic differences between fearful subjects and controls. Mutilation pictures, however, evoked the greatest EMG activity, but only in the fearful group. These data further extend previous research on conscious perception of blood-related stimuli in BII fearful subjects, by showing a failure to recruit autonomic defence responses when blood-related pictures appear outside of conscious awareness. PMID- 22301409 TI - Diastolic dysfunction is associated with myocardial viral load in simian immunodeficiency virus-infected macaques. AB - OBJECTIVE: To establish the relationship between HIV-induced cardiac diastolic dysfunction, immune responses, and virus replication in the heart using the simian immunodeficiency virus (SIV)/macaque model. DESIGN: Cardiac diastolic dysfunction is common in HIV-infected individuals including asymptomatic patients and those treated with combination antiretroviral therapy. SIV-infected macaques develop cardiac dysfunction, serving as a useful model to establish mechanisms underlying HIV-induced cardiac dysfunction. To understand the relationship between functional cardiac impairment, viral replication in the heart, and associated host inflammatory responses, cardiac function was evaluated in SIV infected macaques and functional decline was correlated with features of the host immune response and the extent of viral replication in both the myocardium and plasma. METHODS: Cardiac function was evaluated longitudinally in 22 SIV-infected and eight uninfected macaques using mitral inflow and tissue Doppler echocardiography. Myocardial macrophage populations were evaluated by CD68 and CD163 immunostaining. SIV RNA levels in both myocardium and plasma were measured by qRT-PCR. RESULTS: Echocardiographic abnormalities developed in SIV-infected macaques that closely resembled diastolic dysfunction reported in asymptomatic HIV-infected individuals. Although CD68 and CD163 were upregulated in the myocardium of SIV-infected animals, neither macrophage marker correlated with functional decline. SIV-induced diastolic dysfunction was strongly correlated with extent of SIV replication in the myocardium, implicating virus or viral proteins in the initiation and progression of cardiac dysfunction. CONCLUSION: This study demonstrated a strong correlation between cardiac functional impairment and extent of SIV replication in the myocardium, suggesting that persistent viral replication in myocardial macrophages induces cardiomyocyte damage manifest as diastolic dysfunction. PMID- 22301410 TI - Effect of intermittent interleukin-2 therapy on CD4+ T-cell counts following antiretroviral cessation in patients with HIV. AB - BACKGROUND: Interleukin (IL)-2 therapy impacts T-cell homeostasis. Whether IL-2 expanded CD4(+) T cells may persist following viral rebound has not been fully investigated. METHODS: Patients with CD4(+) T cells 500/MUl or more and HIV RNA less than 50 copies/ml were randomized to continue antiretroviral therapy (ART) either alone (n = 67) or combined with three IL-2 cycles (n = 81; 6 million units) twice daily for 5 days at weeks 0, 8, and 16 before stopping ART (week 24). Patients were followed up to 168 weeks. RESULTS: At week 24, median CD4(+) T cell counts were 1198 and 703 cells/MUl in the IL-2 and control groups, respectively (P < 0.001). At week 72, 27% (IL-2 group) and 45% (control group; P = 0.03) of patients were in failure (defined as no interruption of ART at week 24, CD4 drop below 350 cells/MUl or ART resumption). After week 24, a biphasic decline (before and after week 32) of CD4 was noted -106 and -7 cells/MUl per month in controls and -234 and -17 in IL-2 group (all P <= 0.0001). At week 96, IL-2-expanded CD4(+)CD25(+) T cells remained higher than in the control group (26 vs. 16%, P = 0.006). CONCLUSION: In IL-2-treated patients, CD4(+)CD25(+) T cells persisting despite viral replication allow a longer period of ART interruption. PMID- 22301411 TI - Osteoporotic fracture risk associated with cumulative exposure to tenofovir and other antiretroviral agents. AB - BACKGROUND: Whereas tenofovir (TDF) exposure has been associated with decreased bone density, it remains unclear whether it is associated with increased risk of osteoporotic fractures. METHODS: Patients with any osteoporotic fracture (defined as wrist, vertebral or hip fracture) occurring after HIV diagnosis were identified by International Classification of Diseases - 9th Revision (ICD-9) code in the Veterans Affairs' Clinical Case Registry from 1988 to 2009. Osteoporotic fracture risk associated with cumulative exposure to TDF and other antiretrovirals was examined in univariate analysis and multivariate model 1 (MV1 - controlling for race, age, tobacco use, diabetes, body mass index, and hepatitis C status) and model 2 (MV2 - controlling for MV1 variables + concomitant antiretroviral exposures). RESULTS: Among 56,660 patients evaluated, TDF exposure (total 46,062 person-years) was associated with an osteoporotic fracture hazard ratio of 1.080 [95% confidence interval (CI) 1.02-1.15, P < 0.001] in univariate analysis, 1.06 (0.99-1.12) in MV1 and 1.06 (0.99-1.14) in MV2. Among patients entering the cohort in the highly active antiretroviral therapy (HAART) era (n = 32,439), TDF exposure was associated with a yearly hazard ratio for osteoporotic fracture of 1.16 (95% CI 1.08-1.24, P < 0.001) in univariate model, 1.13 (1.05-1.21, P = 0.001) in MV1 and 1.12 (1.03-1.21, P = 0.011) in MV2. Boosted protease inhibitor exposure was associated with hazard ratio of 1.11 (1.05-1.18, P = 0.001) in univariate model, 1.08 (1.01-1.15, P = 0.026) in MV1 and 1.05 (0.97-1.13, P = 0.237) in MV2. Among protease inhibitors, lopinavir/ritonavir (LPV/RTV) had an osteoporotic fracture hazard ratio of 1.09 (CI 1.00-1.20, P = 0.051) in MV2. CONCLUSION: Cumulative exposure to TDF and, among protease inhibitors, LPV/RTV was independently predictive of increased risk of osteoporotic fracture in the HAART era. PMID- 22301412 TI - Novel clinical trial designs for the development of new antiretroviral agents. AB - The resounding success of combination antiretroviral efficacy for both treatment naive and treatment-experienced patients - with 70-90% viral suppression rates in recent studies - has made registration trials for new agents challenging. With the inevitable specter of drug resistance, new agents must have a pathway to approval. The Forum for Collaborative HIV Research obtained input from concerned stakeholders including industry, clinical sciences, community advocacy, and regulatory sciences (Food and Drug Administration and European Medicines Agency) to discuss how safety and efficacy of new agents could be demonstrated. Recognizing the shortfalls of superiority or noninferiority trials in this environment, a new trial design for treatment-experienced patients, minimizing the risk for drug resistance but allowing full assessment of safety, was proposed. The antiviral efficacy of an active investigational drug would be assessed by comparison to placebo as an add-on to a failing regimen in a short, 10-14-day study followed by institution of an optimized background regimen (OBR) in both arms with investigational drug given to all patients. The follow-on stage would assess dose response, safety, durability of initial response, and development of resistance. Additionally, a second safety trial could be conducted comparing patients randomized to the investigational agent with a new OBR to those on a new OBR and placebo. Finally, approval decisions could consider other long-term safety endpoints. Exposing treatment-naive patients to investigational agents remains a controversial issue; stakeholders have different interpretations of risk-benefit for trials in this population that necessitate careful consideration before initiating trials in them. PMID- 22301413 TI - Overall benefit of antiretroviral treatment on the risk of fracture in HIV: nested case-control analysis in a health-insured population. AB - OBJECTIVES: Fractures are common and associated with multiple risk factors. We assessed the risks of fracture associated with time-dependent, differential antiretroviral drug exposures among a cohort of persons with HIV infection. DESIGN: Nested case-control study from an HIV cohort of 59,594 medically insured persons with HIV infection enrolled in a medical care between January 1997 and March 2008. METHODS: Cases were participants with a low-impact, nontraumatic fracture identified by ICD-9-CM codes; noncases were 1:4 matched and without fracture. RESULTS: Cases included 2,477 persons with HIV infection with fractures, who were risk-set matched to 9,144 persons with HIV infection without fractures. Exposure to antiretroviral therapy by drug class and by duration (any drug/class) was associated with reduced risk for fracture. Drug-specific antiretroviral exposures over time identified an increased risk for fracture associated with darunavir, delavirdine and saquinavir, whereas reduced risk was associated with efavirenz, emtricitabine, lamivudine, tenofovir, and zidovudine. An initial null risk became a reduced risk with increased duration for nevirapine. In a similar pattern, abacavir, didanosine, nelfinavir, ritonavir and stavudine were initially associated with increased risk for fracture, after which the risk became null with increased duration of exposure. Null or uncertain risk for fracture was associated with amprenavir, atazanavir, enfuvirtide, fosamprenavir, indinavir, lopinavir, tipranavir, and zalcitabine. CONCLUSION: Our findings suggest an overall reduced risk for facture in persons treated versus not treated with antiretroviral drugs for HIV infection. Differential drug specific exposure-response relationships for fracture will need to be further evaluated in other study populations. PMID- 22301414 TI - Pathogen prevalence may determine maintenance of antigen-specific T-cell responses in HIV-infected individuals. AB - OBJECTIVE: To assess the effect of antigen-exposure on the T-cell repertoire in the chronic phase of HIV-infection. DESIGN: This is a prospective cross-sectional study. METHODS: HIV-seropositive patients and immunocompetent controls from tuberculosis low and high-endemic countries were recruited. Mycobacterium tuberculosis (purified protein derivative; PPD)-specific CD4 T-cell responses were quantified directly from whole blood using flow-cytometric analysis of intracellular cytokines after specific stimulation. T-cell reactivity toward cytomegalovirus (CMV) or Staphylococcus aureus Enterotoxin B (SEB) served as control. RESULTS: In a low-endemic region, HIV-seropositive patients showed lower frequencies of PPD-specific T cells compared to immunocompetent individuals. This was not due to a general loss of immunity toward recall antigens, as T-cell immunity toward CMV or SEB was preserved. In line with continuous antigen exposure, HIV-seropositive patients from a high-endemic region showed preserved PPD-specific T-cell frequencies that were not different from those found in HIV seronegative controls. Likewise, both groups did not differ in recall T-cell responses toward CMV or SEB. CONCLUSION: A lower prevalence and frequency of PPD specific immunity is a typical feature of HIV-related immunosuppression in low endemic regions. In contrast, PPD-specific responses are maintained in HIV seropositive individuals in regions with high tuberculosis prevalence. This suggests constant skewing and restriction of specific T-cell immunity toward environmental antigens in HIV-seropositive individuals. PMID- 22301415 TI - Elevated cytokine and chemokine levels in the placenta are associated with in utero HIV-1 mother-to-child transmission. AB - OBJECTIVE: To determine whether there is an association between cytokine and chemokine levels in plasma isolated from the placenta and HIV-1 mother-to-child transmission (MTCT). DESIGN: We designed a case-control study of HIV-infected, pregnant women enrolled in the Malaria and HIV in Pregnancy cohort. Participants were recruited in Blantyre, Malawi, from 2000 to 2004. Patients were women whose children were HIV-1 DNA-positive at birth (in-utero MTCT) or HIV-1 DNA-negative at birth and HIV-1 DNA-positive at 6 weeks postpartum (intrapartum MTCT); controls were women whose children were HIV-1 DNA-negative both at birth and 6 weeks postpartum. METHODS: After delivery, blood was isolated from an incision on the basal plate of the placenta. We used a Bio-Plex human cytokine assay (Bio Rad, Hercules, California USA) to simultaneously quantify 27 cytokines, chemokines and growth factors in placental plasma. HIV-1 RNA copies were quantified with the Roche Amplicor kit. RESULTS: Levels of interleukin (IL) 4, IL 5, IL-6, IL-7, IL-9, eotaxin, IL-1Ra and interferon gamma-induced protein 10 (IP 10) were significantly elevated in placental plasma isolated from cases of in utero HIV-1 MTCT. In contrast, only granulocyte colony-stimulating factor was elevated in placental plasma isolated from cases of intrapartum MTCT. After adjusting for maternal age, gestational age and peripheral CD4(+) T-cell count, every log(10) increase in placental IP-10 was associated with a three-fold increase in the prevalence of in-utero HIV-1 MTCT. CONCLUSION: Elevated cytokine and chemokine levels in placental plasma were associated with in-utero and not intrapartum MTCT. IP-10, which is both a T-cell chemokine and potentiator of HIV replication, was robustly and independently associated with prevalent, in-utero MTCT. PMID- 22301416 TI - CD4 T-cell regeneration in HIV-1 elite controllers. AB - BACKGROUND: Elite controllers spontaneously control HIV-1 replication, which in many cases is associated with preservation of normal CD4 T-cell counts. However, a subset of elite controllers has progressive CD4 T-cell losses despite undetectable viral loads, for reasons that remain undefined. Here, we assessed mechanisms of CD4 T-cell homeostasis in elite controllers with progressive vs. nonprogressive HIV-1 disease courses. METHODS: Flow cytometry assays were used to determine the proliferation, activation and apoptosis levels of naive T cells in elite controllers with high or low CD4 T-cell counts and reference cohorts of HIV 1-negative and HAART-treated persons. Thymic output was measured by single-joint T-cell receptor excision circle (sjTREC)/beta T-cell receptor excision circle (betaTREC) ratios, and the frequency of circulating recent thymic emigrants was flow cytometrically determined by surface expression of protein tyrosine kinase 7. RESULTS: Proportions of naive T cells in elite controllers were severely reduced and closely resemble those of HIV-1 patients with progressive disease. Despite reductions in naive T cells, most elite controllers were able to maintain normal total CD4 T-cell counts by preservation of uncompromised thymic function in conjunction with extrathymic processes that led to elevated levels of circulating recent thymic emigrants. In contrast, elite controllers with low CD4 T-cell counts had reduced thymic output that mirrored thymic dysfunction during untreated progressive HIV-1 infection. CONCLUSION: These results indicate that both thymic and extrathymic mechanisms contribute to CD4 T-cell maintenance in elite controllers and support the idea that CD4 T-cell homeostasis and control of viral replication are distinct but frequently coinciding processes. PMID- 22301417 TI - Nevirapine pharmacokinetics and risk of rash and hepatitis among HIV-infected sub Saharan African women. AB - OBJECTIVES: To estimate nevirapine (NVP) pharmacokinetics and examine its association with rash and/or hepatotoxicity in women starting antiretroviral treatment in the AIDS Clinical Trials Group A5208/OCTANE study in Africa. DESIGN: In HIV-infected, nonpregnant women with screening CD4 cell count less than 200 cells/MUl randomized to NVP (twice daily, after 14-day once-daily lead-in period) and tenofovir/emtricitabine, single NVP blood samples were collected 14 and 28 days following randomization. Rash and hepatotoxicity that occurred during therapy, or within 7 days after the last dose of NVP, were defined as toxicity. METHODS: NVP pharmacokinetics were modeled by population pharmacokinetic analysis. Individual Bayesian pharmacokinetic estimates were used to calculate clearance, 24-h area under the curve, and predicted plasma concentrations. RESULTS: Median week 4 NVP clearance was 2 l/h. Among the 359 women, 194 (54%) developed a rash of any grade; 82 (23%) had grade 2+ and nine (3%) had grade 3+ rash. Median clearance was 1.7 l/h for participants exhibiting 3+ rash versus 2 l/h in women without 3+ rash (P = 0.046). The odds of developing 3+ rash was 50% higher for every 20% decrease in clearance (P = 0.046). NVP discontinuation due to rash/liver toxicity was significantly more common among women with pretreatment CD4 cell count more than 250 cells/MUl (P = 0.003). CONCLUSION: In this study, HIV-infected African women starting a NVP-based antiretroviral regimen had a lower NVP clearance compared to previous reports. Severe rash, but not hepatotoxicity, was associated with higher NVP exposure. Albeit observed in a small number of women, baseline CD4 cell count at least 250 cells/MUl was significantly associated with NVP toxicity. PMID- 22301418 TI - Survival of rat functional dental pulp cells in vascularized tissue engineering chambers. AB - Regenerative endodontics aims to preserve, repair or regenerate the dental pulp tissue. Dental pulp stem cells, have a potential use in dental tissue generation. However, specific requirements to drive the dental tissue generation are still obscured. We established an in vivo model for studying the survival of dental pulp cells (DPC) and their potential to generate dental pulp tissue. DPC were mixed with collagen scaffold with or without slow release bone morphogenic protein 4 (BMP-4) and fibroblast growth factor 2 (FGF2). The cell suspension was transplanted into a vascularized tissue engineering chamber in the rat groin. Tissue constructs were harvested after 2, 4, 6, and 8 weeks and processed for histomorphological and immunohistochemical analysis. After 2 weeks newly formed tissue with new blood vessel formation were observed inside the chamber. DPC were found around dentin, particularly around the vascular pedicle and also close to the gelatin microspheres. Cell survival, was confirmed up to 8 weeks after transplantation. Dentin Sialophosphoprotein (DSPP) positive matrix production was detected in the chamber, indicating functionality of dental pulp progenitor cells. This study demonstrates the potential of our tissue engineering model to study rat dental pulp cells and their behavior in dental pulp regeneration, for future development of an alternative treatment using these techniques. PMID- 22301420 TI - Environmental stress responsive expression of the gene li16 in Rana sylvatica, the freeze tolerant wood frog. AB - Wood frogs (Rana sylvatica) can endure weeks of subzero temperature exposure during the winter with up to 65% of their body water frozen as extracellular ice. Associated with freezing survival is elevated expression of a number of genes/proteins including the unidentified gene, li16, first described in liver. The current study undertakes a broad analysis of li16 expression in response to freezing in 12 tissues of wood frogs as well as expression responses to anoxia and dehydration. Transcript levels of li16 increased significantly after 24h freezing (at -2.5 degrees C) demonstrating increases of approximately 3-fold in testes, greater than 2-fold in heart, ventral skin and lung, and over 1.5-fold in brain, liver and hind leg muscle as compared to unfrozen controls at 5 degrees C. Increased li16 transcript levels in brain, muscle and heart were mirrored by elevated Li16 protein in frozen frogs. Significant upregulation of li16 in response to both anoxia and dehydration (both components of freezing) was demonstrated in brain, kidney and heart. Overall, the results indicate that Li16 protein has a significant role to play in cell/organ responses to freezing in wood frogs and that its up-regulation may be linked with oxygen restriction that is a common element in the three stress conditions examined. PMID- 22301419 TI - Persufflation (or gaseous oxygen perfusion) as a method of organ preservation. AB - Improved preservation techniques have the potential to improve transplant outcomes by better maintaining donor organ quality and by making more organs available for allotransplantation. Persufflation, (PSF, gaseous oxygen perfusion) is potentially one such technique that has been studied for over a century in a variety of tissues, but has yet to gain wide acceptance for a number of reasons. A principal barrier is the perception that ex vivo PSF will cause in vivo embolization post-transplant. This review summarizes the extensive published work on heart, liver, kidney, small intestine and pancreas PSF, discusses the differences between anterograde and retrograde PSF, and between PSF and other conventional methods of organ preservation (static cold storage, hypothermic machine perfusion). Prospective implications of PSF within the broader field of organ transplantation, and in the specific application with pancreatic islet isolation and transplant are also discussed. Finally, key issues that need to be addressed before PSF becomes a more widely utilized preservation strategy are summarized and discussed. PMID- 22301421 TI - Utility of exercise stress echocardiography in pediatric cardiac transplant recipients: a single-center experience. AB - BACKGROUND: Annual coronary angiography (ANG) to assess for significant epicardial coronary artery disease (CAD) is an integral part of follow-up care for pediatric cardiac transplant recipients at Children's Hospital Boston. Exercise stress echocardiography (ESE) is an important, non-invasive tool for the detection of ischemia in adults but has been rarely used in children. Therefore, the aim of this study was to assess the feasibility and utility of ESE in excluding ANG-detected epicardial CAD at our center, where ESE has been implemented since 2007. METHODS: We conducted a retrospective review of all pediatric cardiac transplant recipients at our institution who had undergone ESE and ANG between January 2007 and December 2010, and with testing performed < 12 months apart. ESE results were compared against ANG. RESULTS: The study cohort comprised 47 cardiac transplant recipients. One patient's ESE images were inadequate for interpretation. Of the remaining 46 patients, ESE had a sensitivity of 88.9% (95% confidence limits [CL], 51.8%, 99.7%), a specificity of 91.9% (95% CL, 71.8%, 98.3%), and a negative predictive value of 97% (95% CL, 85.1%, 99.1%) for the ANG-detected CAD. CONCLUSIONS: This large, single-center study showed ESE was feasible and had a high specificity and excellent negative predictive value in excluding epicardial CAD in pediatric cardiac transplant recipients. Future prospective, large-scale studies are needed to confirm these findings and help identify a subset of children for whom a negative ESE could decrease the frequency of routine ANG. PMID- 22301422 TI - The role of the Heart Failure Survival Score and psychosocial stress in predicting event-free survival in patients referred for heart transplantation. PMID- 22301423 TI - A two-stage reverse dialysis in vitro dissolution testing method for passive targeted liposomes. AB - A novel two-stage reverse dialysis method has been developed for in vitro release testing of liposomal drug product with passive targeting characteristics. The first stage of the test is to mimic the circulation of liposomes in the body, whereas the second stage is to imitate the drug release process at the target. Buffer and surfactant solution were used during the first and second stages, respectively. For formulations containing high phase transition temperature lipids and high cholesterol content, no drug leakage was observed during the first stage of test. In the second stage, however, formulations with different compositions showed significant differences in terms of drug release rate, and discriminatory ability of the method was demonstrated. On comparing two different membrane diffusion techniques, dialysis and reverse dialysis methods, the reverse dialysis method showed significantly lower variation, and therefore is the preferred method. The developed in vitro release testing method should help to distinguish formulations with varied compositions for quality control testing purposes. This two-stage reverse dialysis method may pave the way to the development of more bio-relevant release testing methods for liposomal drug products. PMID- 22301424 TI - Anticancer efficacy, tissue distribution and blood pharmacokinetics of surface modified nanocarrier containing melphalan. AB - The objectives of the present study were to circumvent the moisture-associated instability, enhance bioavailability and achieve enhanced passive targeting of melphalan to the ovaries. Solubility of the drug was determined in various excipients to select the components of nanoemulsion. Pseudoternary phase diagrams were constructed using aqueous titration method. Formulations selected from the pseudoternary phase diagram were subjected to thermodynamic stability and dispersibility studies to select the final test formulations which were characterized for average globule size, polydispersity index (PDI), zeta potential, viscosity, refractive index, in-vitro drug release and percentage transmittance to optimize the final formulation. Pharmacokinetic and biodistribution studies of the optimized formulation in comparison to the pure drug suspension were done using gamma-scintigraphy on female Balb/c mice. In vitro cytotoxicity study on Hela cervical cancer cell lines was also done to compare the anticancer activity of the developed formulation with respect to the pure drug solution. In vitro-in vivo correlation was established for the amount of drug released and the amount of drug absorbed using suitable deconvolution. Stability studies on the final formulation were performed at 40 +/- 2 degrees C and 75 +/- 5% RH for 3 months and the shelf life was determined. Capmul MCM, Tween 80 and Transcutol P (S(mix)) were selected as the oil, surfactant and co surfactant respectively on the basis of solubility studies. Out of 17 formulations prepared, six formulations were selected as the final test formulations on the basis of thermodynamic stress and dispersibility tests. The optimized formulation composed of oil (10%, v/v), S(mix) (35%, v/v), and double distilled water (55%, v/v). Bioavailability studies revealed 4.83 folds enhancement in bioavailability of the drug from nanoemulsion as compared to that from suspension. Biodistribution studies revealed more than 2 folds increase in uptake of the drug from nanoemulsion by ovaries as compared to that from the suspension. In vitro cytotoxicity studies demonstrated augmented anticancer potential of the drug in the form of nanoemulsion formulation in comparison to the drug solution. Level A correlation was established between the amount of drug released and the amount of drug absorbed. The shelf life of the formulation was found to be 1.30 years. The results demonstrate surface modified nanoemulsion to be a promising approach so as to increase stability, bioavailability and cellular uptake of the drug. PMID- 22301425 TI - Nanoporous multilayer poly(L-glutamic acid)/chitosan microcapsules for drug delivery. AB - Nanoporous poly(L-glutamic acid)/chitosan (PLGA/CS) multilayer microcapsules were fabricated by layer-by-layer (LbL) assembly using the porous silica particles as sacrificial templates. The LbL assembled nanoporous PLGA/CS microcapsules were characterized by Zeta-potential analyzer, FTIR, TGA, SEM, TEM and CLSM. 5 Fluorouracil (5-FU) was chosen as model drug. The drug loading content of PLGA/CS microcapsules depends on loading time, loading temperature, pH value and NaCl concentration. High loading capacity of microcapsules can be achieved by simply adjusting pH value and salt concentration. Moreover, 5-Fu loaded microcapsules take on a sustained release behavior, especially in an acid solution, in contrast to burst release of bare 5-Fu. The kinetics of 5-Fu release from PLGA/CS microcapsules conforms to Korsmeyer-Peppas and Baker-Lonsdale models, the mechanism of which can be ascribed to priority of drug diffusion and subordination of polymer degradation. The MTT cytotoxicity assay in vitro reveals the satisfactory anticancer activity of the drug-loaded PLGA/CS microcapsules. Therefore, the novel nanoporous PLGA/CS microcapsules is expected to find application in drug delivery systems. PMID- 22301426 TI - Dry powder inhalers of gentamicin and leucine: formulation parameters, aerosol performance and in vitro toxicity on CuFi1 cells. AB - The high hygroscopicity of gentamicin (G) as raw material hampers the production of respirable particles during aerosol generation and prevents its direct use as powder for inhalation in patients suffering from cystic fibrosis (CF). Therefore, this research aimed to design a new dry powder formulation of G studying dispersibility properties of an aminoacid, L-leucine (leu), and appropriate process conditions. Spray-dried powders were characterized as to water uptake, particle size distribution, morphology and stability, in correlation with process parameters. Aerodynamic properties were analyzed both by Single Stage Glass Impinger and Andersen Cascade Impactor. Moreover, the potential cytotoxicity on bronchial epithelial cells bearing a CFTR F508/F508 mutant genotype (CuFi1) were tested. Results indicated that leu may improve the aerosol performance of G-dried powders. The maximum fine particle fraction (FPF) of about 58.3% was obtained when water/isopropyl alcohol 7:3 system and 15-20% (w/w) of leu were used, compared to a FPF value of 13.4% for neat G-dried powders. The enhancement of aerosol efficiency was credited both to the improvement of the powder flowability, caused by the dispersibility enhancer (aminoacid), and to the modification of the particle surface due to the influence of the organic co solvent on drying process. No significant degradation of the dry powder was observed up to 6 months of storage. Moreover, particle engineering did not affect either the cell viability or cell proliferation of CuFi1 over a 24 h period. PMID- 22301427 TI - An evaluation of process parameters to improve coating efficiency of an active tablet film-coating process. AB - Effects of material and manufacturing process parameters on the efficiency of an aqueous active tablet film-coating process in a perforated pan coater were evaluated. Twenty-four batches representing various core tablet weights, sizes, and shapes were coated at the 350-500 kg scale. The coating process efficiency, defined as the ratio of the amount of active deposited on tablet cores to the amount of active sprayed, ranged from 86 to 99%. Droplet size and velocity of the coating spray were important for an efficient coating process. Factors governing them such as high ratios of the suspension spray rate to atomization air flow rate, suspension spray rate to pattern air flow rate, or atomization air flow rate to pattern air flow rate improved the coating efficiency. Computational fluid dynamics modeling of the droplets showed that reducing the fraction of the smaller droplets, especially those smaller than 10 MUm, resulted in a marked improvement in the coating efficiency. Other material and process variables such as coating suspension solids concentration, pan speed, tablet velocity, exhaust air temperature, and the length of coating time did not affect the coating efficiency profoundly over the ranges examined here. PMID- 22301428 TI - Indomethacin uptake into poly(2-hydroxyethyl methacrylate-co-3,9-divinyl-2,4,8,10 tetraoxaspiro [5.5]-undecane) network: In vitro and in vivo controlled release study. AB - Networks based on poly(2-hydroxyethyl methacrylate-co-3,9-divinyl-2,4,8,10 tetraoxaspiro [5.5]-undecane), synthesized through radical dispersion polymerization, were used as template for indomethacin (INN) as model drug. The copolymers were characterized by swelling studies at three pH values (2.4, 5.5 and 7.4) and two temperatures (room temperature 24 degrees C and physiological temperature 37 degrees C). Fourier transform infrared (FTIR) spectroscopic analysis was used to sustain the copolymer structures. Scanning electron microscopy (SEM) and thermogravimetric (TG) investigations were used to examine microstructure and appreciate the thermal stability of the polymer samples. The studies of the INN drug release from the copolymer networks were in vitro performed. The in vivo study results (biocompatibility tests, somatic nociceptive experimental model (tail flick test) and visceral nociceptive experimental model (writhing test)) are also reported in this paper. PMID- 22301429 TI - Lower limb lengthening and deformity correction using the Fitbone motorized nail system in the adolescent patient. AB - Leg lengthening by an external fixation is associated with various difficulties. Pin-tract infections are commonly encountered, and muscle contractures and joint stiffness are additional complications associated with this method. Several researchers explored a purely intramedullary solution for leg lengthening since the 1970s. The purpose of this study was to evaluate the results of 10 adolescent patients who underwent leg lengthening with a motorized intramedullary lengthening device (the Fitbone System). We aimed to evaluate the effectiveness of the Fitbone system in deformity correction and lengthening of the femur and tibia in the pediatric and adolescent patients looking at whether the incidence of complications commonly associated with external fixators could be reduced. We compared our preliminary results with those from other reports, with a focus on leg length achieved and rate of complications. Ten patients were included, nine femoral nails and five tibial nails were implanted. The average lengthening distance was 4.8 cm (range, 2.8-10 cm). In 10 patients, leg lengthening was combined with successful correction of the mechanical axis alignment in three patients. The consolidation index averaged 24 days/cm (range, 20-39 days/cm). The average hospital stay was 8 days. No bone or soft tissue infections were observed. Only one patient had irritation and pain from the antenna system after lengthening and recovered fully after antenna removal. Our results suggest that the difficulties commonly associated with external fixators can be reduced with this method. It also allows good angular correction in patients with mechanical axis deviation. These features combined with a short time of hospitalization make it a promising procedure for limb lengthening in adolescent patients. PMID- 22301430 TI - A hip resurfacing implant in an adolescent with cerebral palsy. AB - Pain or skin irritation due to the femoral stump after proximal femoral resection for chronic spastic hip dislocation in children with severe cerebral palsy may be encountered. We describe a technique that, to our knowledge, has been unreported earlier and can deal with this phenomenon to improve the patient's comfort level and help the patient to sit more comfortably. PMID- 22301431 TI - Metachronous aneurysmal bone cyst in a 9-year-old boy: case report and review of the literature. AB - Aneurysmal bone cyst (ABC) is a locally aggressive, benign bone tumor that commonly affects children. Metachronous ABCs are rare, and have been described only three times in the literature. Here we present a fourth case in a 9-year-old boy who presented with an ABC of the scapula; 21/2 years later he presented with a tibial ABC. We also review the literature and discuss the pathological and clinical characteristics of this lesion. PMID- 22301432 TI - Safe care spaces and places: exploring urban Aboriginal families' access to preventive care. AB - Many Aboriginal children living in Canadian cities experience high levels of perinatal and infant health challenges. Despite efforts to reduce inequities in early childhood development, numerous urban Aboriginal families have poor access to preventive care. In this paper, we challenge conventional notions of access and use a postcolonial population health perspective to explain how access to preventive care for Aboriginal families is influenced by safety and responsiveness within care experiences. We explore an approach to care that addresses the safety of care spaces and care places. The potential of this approach for improving access to preventive services for Aboriginal families may be of considerable interest to urban preventive health policy or health system managers. PMID- 22301433 TI - Reduced miR-31 and let-7 maintain the balance between differentiation and quiescence in lung cancer stem-like side population cells. AB - Recent studies have indicated that side population (SP) cells, which are an enriched source of cancer stem cells (CSCs), drive and maintain many types of human malignancies. SP cells have distinguishing biological characteristics and are thought to contribute to metastasis, therapy resistance, and tumor recurrence. In the present study, the miRNA expression profiles of SP cells and non-SP cells were compared using miRNA array analysis. Both let-7 and miR-31 were significantly down-regulated in SP cells compared to non-SP cells. The results were confirmed by real-time PCR. Engineered repression of miR-31 caused marked repression of both lung cancer SP cell and non-SP cell growth in vitro. In contrast, engineered repression of let-7 caused marked promotion of both lung cancer SP and non-SP cells growth in vitro. Cell cycle studies further revealed that reduced miR-31 could inhibit SP cell proliferation by a cell cycle arrest in the G0/G1 phase, whereas reduced let-7 induced SP cell proliferation by accelerating G1/S phase transition. Notably, reduced miR-31 prevented SP cell differentiation, whereas reduced let-7 promoted SP cell differentiation under differentiation conditions. These findings indicate that reduced miR-31 and let-7 are involved in maintaining the balance between differentiation and quiescence in SP cells. PMID- 22301434 TI - Serotonin transporter gene, stress and raphe-raphe interactions: a molecular mechanism of depression. AB - Reports of gene-environment interactions (GxE) between the serotonin transporter gene and stress on risk of depression have generated both excitement and controversy. The controversy persists in part because a mechanistic account of this GxE on serotonergic neurotransmission and risk of depression has been lacking. In this Opinion, we draw on recent discoveries in the functional neuroanatomy of the serotonergic dorsal raphe nucleus (DR) to propose such a mechanistic account. We argue that genetically produced variability in serotonin reuptake during stressor-induced raphe-raphe interactions alters the balance in the amygdala-ventromedial prefrontal cortex (VMPFC)-DR circuitry underlying stressor reactivity and emotion regulation. In particular, the recently characterized stressor-responsive serotonergic interneurons originating from the dorsolateral DR may hold a key to unlocking the GxE mechanism of depression. PMID- 22301435 TI - Association between nerve growth factor gene polymorphism and executive dysfunction in Japanese patients with early-stage Alzheimer's disease and amnestic mild cognitive impairment. AB - BACKGROUND/AIMS: To address the clinical neurocognitive roles of nerve growth factor (NGF) genetic polymorphism in early-stage Alzheimer's disease (AD) and amnestic mild cognitive impairment (A-MCI), we investigated the association between this single-nucleotide polymorphism (SNP) and executive dysfunction as a nonmemory cognitive impairment. METHODS: Among 200 outpatients with dementia and MCI whose NGF SNP rs6330 genotype was identified, those with A-MCI (n = 35) and early-stage AD (n = 67) were recruited and divided into three groups according to genotype (C/C: n = 58, C/T: n = 39, T/T: n = 5). Then, the Frontal Assessment Battery (FAB) scores were compared among the three (C/C, C/T, T/T) or two (C/C, T carrier) genotype groups. RESULTS: Among the subtests, a significant difference was only noted for the go/no-go scores (p < 0.01) between C/C and T carriers. However, no significant differences in the demographic variables and other neuropsychological subtest scores reflecting attentional and memory function were observed among the genotypes. CONCLUSION: Regarding the functional roles of neurotrophin polymorphisms as they relate to executive dysfunction, the NGF gene rs6330 might influence the inhibition task in Japanese patients with early-stage AD or A-MCI. PMID- 22301436 TI - High-throughput approaches for the analysis of extrinsic regulators of stem cell fate. AB - The complexity of stem cell niches poses a tremendous challenge to understanding mechanisms of extrinsic regulation of stem cell fate. In order to better understand niche signaling and its effect on stem cell fate choices, in vitro systems are being engineered which recapitulate, in a simplistic but increasingly sophisticated manner, native stem cell niches. New technologies or new combinations of existing technologies allow more systematic ways to probe niche signaling in high-throughput. Systems biology approaches in experimental design, data acquisition and analysis will be necessary to tackle the challenges that lie ahead. PMID- 22301437 TI - Nucleofection induces transient eIF2alpha phosphorylation by GCN2 and PERK. AB - Nucleofection permits efficient transfection even with difficult cell types such as primary and non-dividing cells, and is used to deliver various nucleic acids, including DNA, mRNA, and small interfering RNA. Unlike DNA and small interfering RNA, mRNA is subject to rapid degradation, which necessitates instant early translation following mRNA delivery. We examined the factors that are important in translation following nucleofection and observed rapid phosphorylation of eukaryotic initiation factor 2 alpha (eIF2alpha) following nucleofection, which occurred in the absence of the delivered nucleic acid. We studied the involvement of three ubiquitous kinases capable of phosphorylating eIF2alpha in mammalian cells and identified that nucleofection-mediated phosphorylation of eIF2alpha was dependent on general control non-derepressible 2 (GCN2) and RNA-dependent protein kinase (PKR)-like endoplasmic reticulum kinase (PERK) but not PKR. A reduction in translation due to eIF2alpha phosphorylation was observed post nucleofection, demonstrating functional significance. Understanding the impact of nucleofection on translational machinery has important implications for therapeutics currently under development based on the delivery of mRNA, DNA, and small interfering RNA. Strategies to circumvent eIF2alpha phosphorylation and other downstream effects of activating GCN2 and PERK will facilitate further advancement of nucleic acid based therapies. PMID- 22301438 TI - Cardiac gene therapy in large animals: bridge from bench to bedside. AB - Several clinical trials are evaluating gene transfer as a therapeutic approach to treat cardiac diseases. Although it has just started on the path to clinical application, recent advances in gene delivery technologies with increasing knowledge of underlying mechanisms raise great expectations for the cardiac gene therapy. Although in vivo experiments using small animals provide the therapeutic potential of gene transfer, there exist many fundamental differences between the small animal and the human hearts. Before applying the therapy to clinical patients, large animal studies are a prerequisite to validate the efficacy in an animal model more relevant to the human heart. Several key factors including vector type, injected dose, delivery method and targeted cardiac disease are all important factors that determine the therapeutic efficacy. Selecting the most optimal combination of these factors is essential for successful gene therapy. In addition to the efficacy, safety profiles need to be addressed as well. In this regard, large animal studies are best suited for comprehensive evaluation at the preclinical stages of therapeutic development to ensure safe and effective gene transfer. As the cardiac gene therapy expands its potential, large animal studies will become more important to bridge the bench side knowledge to the clinical arena. PMID- 22301439 TI - Evolution of HIV-1 genotype in plasma RNA and peripheral blood mononuclear cells proviral DNA after interruption and resumption of antiretroviral therapy. AB - BACKGROUND: Structured antiretroviral therapy interruption (TI) is discouraged because of poorer AIDS and non-AIDS-related outcomes, but is often inevitable in clinical practice. Certain strategies could reduce the emergence of resistance mutations related to TI. METHODS: A total of 106 HIV-1-infected patients on stable HAART with undetectable plasma viral load were randomized to therapy continuation (n=50) or CD4(+) T-cell-guided TI (n=56). Staggered interruption involved stopping non-nucleoside reverse transcriptase inhibitors (NNRTIs) 7 days before the nucleoside backbone. Genotypic resistance testing (GRT) was performed on proviral DNA from peripheral blood mononuclear cells (PBMCs) at baseline and before each TI, and on plasma RNA after each TI. RESULTS: At baseline, GRT on PBMCs detected mutations in nine patients and only two major mutations were identified. GRT on plasma samples performed after TIs showed nucleoside reverse transcriptase inhibitors (NRTI), NNRTI and protease inhibitor major resistance associated mutations in 10/56, 3/46 and 1/8 patients receiving these drugs, respectively. Only in two patients had the same mutations been observed in GRT on PBMCs at baseline. Three patients presented virological failure after resumption of therapy, all receiving NNRTIs. In one of them, resistance mutations detected at failure had been also observed previously in GRT on plasma after TI. CONCLUSIONS: Staggered interruption of NNRTIs 7 days before the nucleoside backbone does not avoid resistance emergence completely, but does not necessarily lead to virological failure after treatment resumption. Plasma HIV-1 RNA genotype after the interruption and the patient's treatment history seem to be more useful than baseline proviral DNA genotype to assess the risk of virological failure after restarting therapy. PMID- 22301440 TI - Serum levels of the ovarian cancer biomarker HE4 are decreased in pregnancy and increase with age. AB - OBJECTIVE: The purpose of this study was to establish normal ranges for human epididymis protein 4 (HE4) serum levels in healthy women. STUDY DESIGN: HE4 levels were measured in healthy women and analyzed by age, menopausal status, and pregnancy status. Upper 95th percentiles were determined for normal ranges. RESULTS: Serum samples from 1101 healthy women and 67 pregnant women were analyzed. Above the age of 40 years significant elevations in HE4 concentrations emerged with advancing age. The upper 95th percentile for HE4 levels was 89 pmol/L for premenopausal women, 128 pmol/L for postmenopausal women, and 115 pmol/L for all women. There was a significant difference in the median serum HE4 levels in premenopausal women (46.6 pmol/L) compared with postmenopausal women (57.6 pmol/L; P < .001). In pregnant women, median HE4 concentrations were significantly lower than their premenopausal counterparts (P < .001). CONCLUSION: HE4 serum concentrations vary significantly on the basis of age. These variations must be considered when the upper limit of normal for HE4 is determined. PMID- 22301441 TI - The effects of apolipoproteins E3 and E4 on the transforming growth factor-beta system in targeted replacement mice. AB - BACKGROUND: This study examined the possibility that apolipoprotein E4 (apoE4), the most prevalent genetic risk factor of Alzheimer's disease, interacts isoform specifically with the transforming growth factor (TGF)-beta system. METHODS: This was pursued by measurements of the effects of apoE3 and apoE4 on the levels of TGF-beta ligands and on activation of the Smad system in brains of human apoE targeted replacement mice, utilizing Western blot. RESULTS: The study revealed that apoE4 reduces, isoform specifically, the levels of TGF-beta(1), TGF-beta(2) and TGF-beta(3) in the septum and of TGF-beta(3) in the hippocampus. In contrast, the levels and extent of phosphorylation of Smad1, 5 and 8 as well as of Smad2 and Smad3 in these brain areas were not affected by apoE4, suggesting that the apoE4-driven effects on the TGF-beta system may be mediated via the Smad independent non-canonical pathway. CONCLUSION: The possible role of the TGF-beta system in mediating the pathological effects of apoE4 is discussed. PMID- 22301442 TI - Thoracic ultrasound demonstrates variable location of the intercostal artery. AB - BACKGROUND: Ultrasound (US) guidance is advocated to reduce complications from thoracocentesis or intercostal catheter (ICC) insertion. Although imaging of the intercostal artery (ICA) with Doppler US has been reported, current thoracic guidelines do not advocate this, and bleeding from a lacerated ICA continues to be a rare but serious complication of thoracocentesis or ICC insertion. OBJECTIVES: It was the aim of this study to describe a method to visualise the ICA at routine US-guided thoracocentesis and map its course across the posterior chest wall. METHOD: The ICA was imaged in 22 patients undergoing US-guided thoracocentesis, at 4 positions across the back to the axilla. Its location, relative to the overlying rib, was calculated as the fraction of the intercostal space (ICS) below the inferior border of that rib. RESULTS: An ICA was identified in 74 of 88 positions examined. The ICA migrated from a central 'vulnerable' location within the ICS near the spine (0.28, range 0.21-0.38; p < 0.001) towards the overlying rib (0.08, range 0.05-0.11; p < 0.001) in the axilla. CONCLUSIONS: The ICA can be visualised with US and is more exposed centrally within the ICS in more posterior positions; however, there is a marked variation between individuals, such that the ICA may lie exposed in the ICS even as far lateral as the axilla. Future studies need to identify which patients are at risk for a 'low lying' ICA to further define the role of US imaging of the ICA during thoracocentesis or ICC insertion. PMID- 22301443 TI - Antitumor effect of Croton lechleri Mull. Arg. (Euphorbiaceae). AB - ETHNOPHARMAGOLOGICAL RELEVANCE: Medicinal plants are an important source of antitumor compounds. This study evaluated the acute toxicity in mice, as well as the cytotoxic and antitumoral effects of methanolic extracts of Croton lechleri leaves (CLE). MATERIALS AND METHODS: The cytotoxicity of CLE on human cancer cell lines and human non-cancerous cells was evaluated using the MTT and apoptosis assays. Apoptosis induced by CLE on human cancer cell lines was determined using flow cytometry with annexin-Alexa 488/propidium iodide. The acute toxicity in mice was performed according to the Lorke procedure. Different doses of CLE were injected intraperitoneally daily into athymic mice bearing tumor during 18 days. The growth and weight of tumors was measured. RESULTS: CLE showed low IC(50) values on HeLa (17MUg/ml) cells but lack toxic effects against human normal cells. Induction of cell death in HeLa cells by CLE was confirmed by an increase of apoptosis (Annexin/PI) by 30% compared to untreated cells. The LD(50) was 356mg/kg by intraperitoneal route (i.p.) and 500mg/kg by oral route. CLE administrated at 1, 10 and 50mg/kg i.p. inhibited the tumor growth by 38%, 48% and 59%, respectively, in mice bearing HeLa tumor. CONCLUSION: Croton lechleri shows moderate toxic effects in vivo, exerts cytotoxic effects on HeLa cells and has antitumor effects in mice bearing HeLa tumor. PMID- 22301444 TI - Aqueous extract of Centella asiatica promotes corneal epithelium wound healing in vitro. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Centella asiatica is a traditional herbal medicine that has been shown to have pharmacological effect on skin wound healing, and could be potential therapeutic agent for corneal epithelial wound healing. AIM OF THE STUDY: This study was done to evaluate the effects of Centella asiatica on the proliferation and migration of rabbit corneal epithelial (RCE) cells in the in vitro wound healing model. MATERIALS AND METHODS: RCE cells were cultured with or without supplementation of Centella asiatica aqueous extract. Viability and proliferation of the RCE cells was determined by MTT assay and cell cycle was analyzed by flow cytometry. In vitro re-epithelization was studied by scratch assay and migration rate was evaluated quantitatively by image analyzer. Expression of corneal specific differentiation markers, CK12 and connexin 43, were studied via RT-PCR. RESULTS: It was found that supplementation of Centella asiatica did not show any significant effect on the RCE cells proliferation at the concentration up to 500ppm, while at the concentration of 1000ppm significantly inhibited RCE cells proliferation (p<0.05). However, at the concentration up to 62.5ppm, RCE cells shows significant enhancement of migration rate compared to the control group (p<0.05). It was also found that the supplementation of Centella asiatica aqueous extract did not alter the expression of differentiation markers and cell cycle. CONCLUSION: In conclusion, supplementation of Centella asiatica aqueous extract at low concentrations could be useful to promote corneal epithelium wound healing. PMID- 22301445 TI - Inhibition of human calcineurin and yeast calcineurin-dependent gene expression by Jasminum humile leaf and root extracts. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Jasminum humile are used to treat skin disorders in a way which resembles the use of modern topical anti inflammatory drugs. Ethanolic extracts of the roots and leaves were shown to inhibit calcineurin which is a regulator of inflammatory gene expression. MATERIALS AND METHODS: A novel yeast calcineurin reporter gene assay suitable for a 96 well plate format was developed to test for inhibition of calcineurin dependent gene expression. Calmodulin/calcineurin phosphatase assays were then used to further elucidate the mode of action of the extracts. RESULTS AND CONCLUSIONS: Jasminum humile root and leaf extract exhibited calcineurin inhibition activity that was shown to be mediated through a direct interaction with calcineurin enzyme. The activity is sufficient to block calcineurin dependent gene expression in a yeast model. The activity of the plant supports its traditional use in the treatment of inflammatory skin disorders. The specially adapted yeast reporter assay was found to be a highly effective way of detecting calcineurin inhibitors in plant extracts. PMID- 22301446 TI - A report on anti-oedemogenic activity of Byttneria herbacea roots--possible involvement of histamine receptor (type I). AB - ETHNOPHARMACOLOGICAL RELEVANCE: The traditional healers of the Kol tribes of West Bengal, Bihar and Jharkhand (India), widely use the woody rootstock of Byttneria herbacea to reduce the swelling of limbs, due to filariasis. Besides filariasis different part of this plant is used for the treatment of cholera, diarrhoea and asthma. AIM OF THIS STUDY: This study is a preliminary attempt to evaluate the anti-oedemogenic activity of the roots of Byttneria herbacea. MATERIALS AND METHODS: The anti-oedemogenic activity of the hydroalcoholic extract of the roots of Byttneria herbacea (HBH) was evaluated against carrageenan and histamine induced rat paw oedema, acetic acid induced writhing and histamine induced vascular permeability in mice. Further, the effect of HBH on the expression of human histamine receptor type I (H1R) was studied in HeLa cells. RESULTS: HBH exhibited significant dose-dependent inhibition (*p<0.05) against carrageenan and histamine induced rat paw oedema. Similar significant dose-dependent inhibition was observed against acetic acid induced writhing and histamine-induced vascular permeability in mice. Moreover, H1R specific mRNA expression was also significantly (*p<0.05) suppressed by HBH. CONCLUSION: HBH was observed to possess anti-oedemogenic activity which is probably mediated through suppression of H1R. PMID- 22301447 TI - Anticonvulsant activity of the essential oil and methanolic extract of Bunium persicum (Boiss). B. Fedtsch. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Bunium persicum is an endemic plant to Iran which its seeds have a long history of medicinal uses. AIM OF THE STUDY: This work aimed to study the anticonvulsant effect of the essential oil and methanolic extract of the plant. MATERIALS AND METHODS: The essential oil and methanolic extract of the plant were studied against pentylenetetrazole (PTZ) and maximal electroshock (MES) induced convulsions in mice in different doses. The neurotoxicity of the essential oil and methanolic extract was investigated using rotarod method. RESULTS: The essential oil and methanolic extract prolonged the onset of clonic and tonic seizures in PTZ. The tonic seizures were prevented by essential oil in both methods at dose of 1mL/kg and higher doses. The methanolic extract inhibited PTZ-convulsions at dose 3g/kg and was ineffective against MES induced convulsion. CONCLUSIONS: The essential oil of the plant might be useful to control absence and grand mal seizures at dose 1mL/kg. This activity might be due to its content of monoterpenes. PMID- 22301448 TI - Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Ziziphus extracts have been used in Traditional Chinese Medicine for the treatment of cancer. AIM OF THE STUDY: In the present study we have investigated the effects of Ziziphus jujube extracts (ZEs) on breast cancer. MATERIALS AND METHODS: We evaluated the effects of increasing concentrations of ZEs on ERalpha positive MCF-7 and ERalpha negative SKBR3 breast cancer cell proliferation using MTT assays. Apoptosis was analyzed by evaluating the involvement of some pro-apoptotic proteins, including Bax, Bad, Bid and PARP cleavage by immunoblotting analysis. Moreover, the effects of ZEs treatment on apoptosis were tested by both DNA fragmentation and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) staining. By using chromatographic techniques, we identified the constituents of the effective extracts. RESULTS: ZE1, ZE2, and ZE4 exerted significant antiproliferative effects on estrogen receptor alpha (ERalpha) positive MCF-7 (IC(50) values of 14.42, 7.64, 1.69MUg/mL) and ERalpha negative SKBR3 (IC(50) values of 14.06, 6.21, 3.70MUg/mL) human breast cancer cells. Remarkably, ZEs did not affect cell viability of both normal human fibroblasts BJ1-hTERT and nonmalignant breast epithelial MCF-10A cells. Treatment with ZEs induced cell death by apoptosis in both malignant breast cells. We found that the most effective extracts ZE2 and ZE4 shared a number of triterpenic acids, already known for their anticancer activities. CONCLUSIONS: Our data provide a rational base for the use of Ziziphus extracts in the treatment of breast cancer in Traditional Chinese Medicine. PMID- 22301449 TI - Antimalarial plant remedies from Burkina Faso: their potential for prophylactic use. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Saye, a combination remedy prepared from Cochlospermum planchonii Hook.f. (Cochlospermaceae), Cassia alata L. (Fabaceae) and Phyllanthus amarus Schumach. et Thonn. (Euphorbiaceae), N'Dribala, a Cochlospermum planchonii root decoction, and a fruit preparation of Azadirachta indica A. Juss. (Meliaceae) are plant remedies of the folk medicine in Burkina Faso and are commonly used by traditional healers for the treatment of malaria. AIM OF THE STUDY: This study aimed at validating the antiplasmodial activity of the preparations and at estimating their potential for prophylaxis, using the murine malaria system Plasmodium berghei/Anopheles stephensi. MATERIALS AND METHODS: Aqueous extracts were orally administered to mice (6 animals per treatment group) at a daily dose of 200mg/kg body weight for nine days, applying protocols that mimic as much as possible traditional recipes and treatment schemes. RESULTS: Saye, N'Dribala and Azadirachta indica preparations revealed prophylactic activity, reducing parasitaemia in treated mice, with respect to controls, by 52.0% (CI(95) 46.1-57.9), 45.5% (CI(95) 44.5-46.5) and 45.0% (CI(95) 41.1-48.9), respectively. No evidence of transmission blocking effects was detected with any of the tested remedies. CONCLUSIONS: This study confirms, in the murine malaria system, the antiplasmodial properties of the examined remedies on the Plasmodium stages developing in the vertebrate host, thus encouraging studies aiming at identifying the active fractions and compounds responsible for the described activity and to develop standardized prophylactic remedies. PMID- 22301450 TI - Differential treatment regimen-related effects of HU210 on CB(1) and D(2)-like receptor functionality in the rat basal ganglia. AB - BACKGROUND/AIMS: Functional linkages between the cannabinoid CB(1) and the dopaminergic systems have been reported although the observations and the mechanisms hypothesizing their interactions at the G protein-coupled receptor (GPCR) functionality level are conflicting. METHODS: Administration of a potent cannabinoid agonist, HU210, at various doses (25-100 MUg/kg) and treatment regimens (1- to 14-day treatment) in rats was carried out to investigate the effect of HU210 treatment on the CB(1) and D(2)-like agonist-mediated GPCR activation. RESULTS: The desensitizations (reduced coupling) of both D(2) agonist and CB(1) agonist-mediated GPCR activation was found to be treatment duration dependent and region specific, suggesting implication of receptor tolerance and adaptation due to the cannabinoid treatment. The effect of HU210 on the CB(1) agonist-mediated GPCR desensitization in all treatment groups was not dose dependent. CONCLUSIONS: The desensitization of D(2)-like receptors found after a cannabinoid treatment in this study strengthens the evidence that the two neurotransmitter systems interact at the intercellular level; this interaction might occur via multiple mechanisms, which also vary according to region. PMID- 22301451 TI - Metabolic assessment of intracranial tuberculomas using 11C-methionine and 18F FDG PET/CT. AB - BACKGROUND: 18F-fluorodeoxyglucose (18F-FDG) has limited specificity in the evaluation of intracranial lesions as it is taken up by inflammatory and granulomatous lesions as well. 11C-methionine is known to have a higher specificity in tumor detection, delineation, and differentiation of benign from malignant lesions. However, its uptake in granulomatous lesions remains unclarified. OBJECTIVE: The aim of this study was to explore the value of 11C methionine PET/CT and 18F-FDG in the evaluation of intracranial tuberculomas. METHODS: 11C-methionine PET/CT followed by 18F-FDG PET/CT study was performed on 12 patients with intracranial tuberculomas. The diagnosis was confirmed for all cases on histopathological evaluation and/or follow-up. Quantitative analysis was performed for all cases by measuring the lesion-to-normal gray matter uptake ratio. RESULTS: A high lesion-to-normal gray matter uptake ratio was observed on both 11C-methionine (1.8 +/- 0.38) and 18F-FDG scans (1.64 +/- 0.26) in all newly diagnosed cases. Lesion detection and delineation was superior on 11C-methionine PET/CT. In addition, 11C-methionine appeared to be a more sensitive indicator for assessing early therapeutic response and incomplete therapeutic response in intracranial tuberculomas. There was complete concordance in the number and sites of lesions detected on 11C-methionine PET/CT and radiological imaging modalities (namely, CT and MRI). CONCLUSION: This preliminary study suggests that in newly diagnosed, untreated intracranial tuberculomas, 11C-methionine, like 18F-FDG, may have limited specificity in distinguishing it from a neoplastic lesion. However, it may play an important role in assessing the response to antitubercular treatment. Further studies are warranted to explore the potential of 11C methionine in this regard. PMID- 22301452 TI - Structural properties of Pb2MnW(1-x)Re(x)O6 double perovskites. AB - Pb2MnW(1-x)Re(x)O6 samples have been synthesized and their structure determined by powder x-ray diffraction. These samples undergo a first order structural phase transition between 413 and 445 K depending on the composition. Above this temperature, the samples are cubic. Below the transition temperature, solid solutions are found for x <= 0.2 and x >= 0.5. The W-rich samples adopt an orthorhombic cell whereas the Re-rich compounds are monoclinic. In the intermediate region, 0.2 < x < 0.5, both phases coexist. X-ray absorption spectra did not reveal significant changes in the local structure for Pb, Mn or Re atoms across the structural phase transition. All the atoms exhibit distorted environments in the whole series. In the case of Pb and W(Re) atoms, the local distortion remains in the high temperature phase. Samples with x <= 0.2 also show a sharp discontinuity in the dielectric permittivity at the phase transition temperature indicating the presence of a concomitant electrical ordering in the bulk grains. Such an anomaly in the dielectric constant is not observed for the x >= 0.5 samples, compatible with the lack of dipole ordering for this composition range. The different electrical behaviours also explain the differences in the entropy content for the two types of transition. PMID- 22301453 TI - Beyond the comparator model. PMID- 22301454 TI - Is that what I wanted to do? Cued vocalizations influence the phenomenology of controlling a moving object. AB - The phenomenology of controlled action depends on comparisons between predicted and actually perceived sensory feedback called action-effects. We investigated if intervening task-irrelevant but semantically related information influences monitoring processes that give rise to a sense of control. Participants judged whether a moving box "obeyed" or "disobeyed" their own arrow keystrokes (Experiments 1 and 2) or visual cues representing the computer's choices (Experiment 3). During 1s delays between keystrokes/cues and box movements, participants vocalized directions ("up", "down", "left", or "right") cued by letters inside the box. Congruency of cued vocalizations was manipulated relative to previously selected keystrokes and upcoming box movements. In Experiment 1, reported obey moves and feelings of control reflected the true frequency of obey moves, but were also modulated by vocalizations. Incongruent vocalizations reduced reported obey moves, whereas congruent vocalizations increased them. In Experiment 2, vocalizations had stronger effects when their congruence with primary-task box movement was consistent for several consecutive moves before congruence changed. In Experiment 3, analogous impacts of vocalizations occurred when the computer selected the directions and participants judged whether the computer had control of the box. We conclude that predicted and perceived action effects associated with semantically related but separate and ostensibly irrelevant actions can be conflated with one another. This interference is not restricted to actions performed with the same effector or within the same modality, or even by the same actor. Thus in estimating degrees of control, the mind integrates across ongoing action systems, whether or not they are logically task-relevant. PMID- 22301455 TI - Solvent controlled sugar-rhodamine fluorescence sensor for Cu(2+) detection. AB - A "turn-on" fluorescence probe for Cu(2+) detection has been reported according to a Cu(2+) triggered spirolactam ring-opening reaction. The probe is a double responsive fluorescent and colorimetric Cu(2+)-specific sensor in aqueous solution containing 20% of acetonitrile with high selectivity and excellent sensitivity (limit of detection is 12 MUg L(-1)). Furthermore, the significant color changes visible to the naked eye at the concentration of 3 MUM (ca. 0.20 mg L(-1)) are about ten times lower than the WHO (World Health Organization) recommended level (2.0 mg L(-1)) for Cu(2+) ions in drinking water. PMID- 22301457 TI - Working memory benefits creative insight, musical improvisation, and original ideation through maintained task-focused attention. AB - Anecdotes from creative eminences suggest that executive control plays an important role in creativity, but scientific evidence is sparse. Invoking the Dual Pathway to Creativity Model, the authors hypothesize that working memory capacity (WMC) relates to creative performance because it enables persistent, focused, and systematic combining of elements and possibilities (persistence). Study 1 indeed showed that under cognitive load, participants performed worse on a creative insight task. Study 2 revealed positive associations between time-on task and creativity among individuals high but not low in WMC, even after controlling for general intelligence. Study 3 revealed that across trials, semiprofessional cellists performed increasingly more creative improvisations when they had high rather than low WMC. Study 4 showed that WMC predicts original ideation because it allows persistent (rather than flexible) processing. The authors conclude that WMC benefits creativity because it enables the individual to maintain attention focused on the task and prevents undesirable mind wandering. PMID- 22301461 TI - Characterization and modelling of the heat transfers in a pilot-scale reactor during composting under forced aeration. AB - The paper focused on the modelling of the heat transfers during composting in a pilot-scale reactor under forced aeration. The model took into account the heat production and the transfers by evaporation, convection between material and gas crossing the material, conduction and surface convection between gas and material in bottom and upper parts of the reactor. The model was adjusted thanks to the measurements practised during fifteen composting experiments in which five organic wastes were, each, composted under three constant aeration rates. Heat production was considered proportional to oxygen consumption rate and the enthalpy per mole oxygen consumed was assumed constant. The convective heat transfer coefficients were determined on basis of the continuous measurements of the temperatures of both the lid and the bottom part of the reactor. The model allowed a satisfying prediction of the temperature of the composting material. In most cases, the mean absolute discard between the experimental and the simulated temperatures was inferior to 2.5 degrees C and the peaks of temperature occurred with less than 8h delay. For the half of the experiments the temperature discard between the simulated peak and the experimental one was inferior to 5 degrees C. On basis of the calculation of a stoichiometric production of water through oxidation of the biodegradable organic matter, the simulation of water going out from material as vapour also allowed a rather satisfying prediction of the mass of water in final mixture. The influence of the aeration rate on every type of heat loss was characterized. Finally, the model was used to evaluate the impacts on material temperature caused by the change of the insulation thickness, the ambient temperature, take the lid away, the increase or the decrease of the mass of waste to compost. PMID- 22301462 TI - Self- and informant ratings of personality in mild cognitive impairment, reviewed. AB - AIMS: To examine the degree of agreement between self- and informant ratings of personality in relation to cognitive function in patients with mild cognitive impairment (MCI), subjective cognitive impairment (SCI) and healthy controls (HC). METHODS: Thirty-two patients and informants with MCI, 23 with SCI and 22 HC completed the Swedish universities Scales of Personality (SSP). Correlations and incongruence between self- and informant ratings were calculated. The Mini Mental State Examination (MMSE) was used to assess cognitive function. RESULTS: The correlations between self- and informant ratings were fair-to-moderate on a majority of SSP scales and significant in 44%. The incongruence between patients and informants was significantly larger in MCI than in HC across SSP scales. There was a significant negative correlation between the incongruence index and the MMSE for all subjects. CONCLUSIONS: Self-informant agreement on ratings of patients' personality was reasonable. Incongruence between patients and their informants was associated with MCI but not SCI or HC. Disagreement between patients and informants indicates cognitive impairment. PMID- 22301463 TI - SNP rs11190870 near LBX1 is associated with adolescent idiopathic scoliosis in southern Chinese. AB - A study was conducted to validate the most significant single nucleotide polymorphism (SNP) from a genome-wide association study of Japanese adolescent idiopathic scoliosis (AIS) patients in an independent southern Chinese population. In total, 300 AIS patients fulfilled the clinical criteria and 788 controls with MRI scans of the spine were included in the replication study. We employed case-control analysis to study the association of SNP rs11190870 near LBX1 (ladybird homeobox 1) with AIS in a southern Chinese population. The results suggest that SNP rs11190870 is significantly associated with AIS (P=9.1 * 10( 10); odds ratio=1.85; 95% confidence interval=1.52-2.25). The results of this study confirm that SNP rs11190870 is associated with AIS. PMID- 22301464 TI - A family of oculofaciocardiodental syndrome (OFCD) with a novel BCOR mutation and genomic rearrangements involving NHS. AB - Oculofaciocardiodental syndrome (OFCD) is an X-linked dominant disorder associated with male lethality, presenting with congenital cataract, dysmorphic face, dental abnormalities and septal heart defects. Mutations in BCOR (encoding BCL-6-interacting corepressor) cause OFCD. Here, we report on a Korean family with common features of OFCD including bilateral 2nd-3rd toe syndactyly and septal heart defects in three affected females (mother and two daughters). Through the mutation screening and copy number analysis using genomic microarray, we identified a novel heterozygous mutation, c.888delG, in the BCOR gene and two interstitial microduplications at Xp22.2-22.13 and Xp21.3 in all the three affected females. The BCOR mutation may lead to a premature stop codon (p.N297IfsX80). The duplication at Xp22.2-22.13 involved the NHS gene causative for Nance-Horan syndrome, which is an X-linked disorder showing similar clinical features with OFCD in affected males, and in carrier females with milder presentation. Considering the presence of bilateral 2nd-3rd toe syndactyly and septal heart defects, which is unique to OFCD, the mutation in BCOR is likely to be the major determinant for the phenotypes in this family. PMID- 22301465 TI - Missense mutations in the DNA-binding/dimerization domain of NFIX cause Sotos like features. AB - Sotos syndrome is characterized by prenatal and postnatal overgrowth, characteristic craniofacial features and mental retardation. Haploinsufficiency of NSD1 causes Sotos syndrome. Recently, two microdeletions encompassing Nuclear Factor I-X (NFIX) and a nonsense mutation in NFIX have been found in three individuals with Sotos-like overgrowth features, suggesting possible involvements of NFIX abnormalities in Sotos-like features. Interestingly, seven frameshift and two splice site mutations in NFIX have also been found in nine individuals with Marshall-Smith syndrome. In this study, 48 individuals who were suspected as Sotos syndrome but showing no NSD1 abnormalities were examined for NFIX mutations by high-resolution melt analysis. We identified two heterozygous missense mutations in the DNA-binding/dimerization domain of the NFIX protein. Both mutations occurred at evolutionally conserved amino acids. The c.179T>C (p.Leu60Pro) mutation occurred de novo and the c.362G>C (p.Arg121Pro) mutation was inherited from possibly affected mother. Both mutations were absent in 250 healthy Japanese controls. Our study revealed that missense mutations in NFIX were able to cause Sotos-like features. Mutations in DNA-binding/dimerization domain of NFIX protein also suggest that the transcriptional regulation is abnormally fluctuated because of NFIX abnormalities. In individuals with Sotos like features unrelated to NSD1 changes, genetic testing of NFIX should be considered. PMID- 22301466 TI - Interleukin 28B genetic polymorphisms and viral factors help identify HCV genotype-1 patients who benefit from 24-week pegylated interferon plus ribavirin therapy. AB - BACKGROUND: Interleukin 28B (IL28B) single nucleotide polymorphism (SNP) genotypes and viral factors can predict sustained virological response (SVR) in HCV genotype-1 (HCV-1) patients receiving 48 weeks of pegylated interferon and ribavirin. Whether these factors would identify those patients who can benefit from a shorter duration of therapy remains unclear. METHODS: Treatment-naive HCV 1 patients (n=662) receiving 24 or 48 weeks of combination therapy were enrolled. Baseline demographic data, HCV viral load, IL28B SNP genotypes (rs8099917), duration of therapy and rapid virological response (RVR) were evaluated to predict SVR. The SVR rates were further stratified by the independent factors and compared. RESULTS: The IL28B rs8099917 TT genotype, low baseline viral load (HCV RNA<=600,000 IU/ml), RVR and 48-week therapy independently predicted SVR. In RVR patients with the IL28B rs8099917 TT genotype, the SVR rate of 24-week therapy was comparable to 48-week therapy (95% versus 99%; P=0.21) at low baseline viral load, but was inferior to 48-week therapy (70% versus 97%; P<0.001) at high baseline viral load. In non-RVR patients, the SVR rate of 24-week therapy was inferior to 48-week therapy for those with the IL28B rs8099917 TT genotype but high baseline viral load (23% versus 62%; P<0.001), and those with the IL28B rs8099917 GT/GG genotype but low baseline viral load (0% versus 33%; P=0.02). CONCLUSIONS: HCV-1 patients simultaneously bearing the IL28B rs8099917 TT genotype, low baseline viral load and RVR can benefit from a shorter duration of combination therapy. PMID- 22301467 TI - Neuroinflammation and blood-brain barrier changes in capillary amyloid angiopathy. AB - INTRODUCTION: beta-Amyloid (Abeta) accumulation in cortical capillaries is a variant of cerebral amyloid angiopathy (CAA) referred to as capillary CAA (capCAA). capCAA is associated with a neuroinflammatory response. In vitro studies indicate that Abeta induces reactive oxygen species (ROS) production, mainly generated through NADPH oxidase (NOX), by activated microglia. ROS in turn can induce altered expression of tight junctions (TJ), which are essential for blood-brain barrier (BBB) function. Whether the function of the BBB is affected in the brains of Alzheimer's disease (AD) patients with comorbid capCAA remains elusive. Cases with capCAA and no other AD-related changes allow studying capCAA associated BBB alterations independent of AD pathology. AIM: In this study, we have investigated BBB alterations in capCAA and addressed the role of the neuroinflammatory response. METHODS: Human postmortem brain tissue with capCAA was analyzed by immunohistochemical staining. RESULTS: In this study, we show for the first time a dramatic loss of TJ proteins claudin-5, occludin and ZO-1 in Abeta-laden capillaries. In addition, affected capillaries are associated with clusters of NOX-2-positive activated microglia. Disrupted BBB function was observed by increased presence of fibrinogen around the affected capillaries. CONCLUSIONS: Our data provide support for the early observation that neuroinflammatory response is involved in the altered expression of TJs in endothelial cells and loss of BBB integrity in capCAA. PMID- 22301468 TI - Amelogenin exons 8 and 9 encoded peptide enhances leucine rich amelogenin peptide mediated dental pulp repair. AB - Amelogenins containing exons 8 and 9 are alternatively spliced variants of amelogenin. Some amelogenin spliced variants have been found to promote pulp regeneration following pulp exposure. The function of the amelogenin spliced variants with the exons 8 and 9 remains unknown. In this study, we synthesized recombinant leucine rich amelogenin peptide (LRAP, A-4), LRAP plus exons 8 and 9 peptide (LRAP 8, 9) or exons 8 and 9 peptide (P89), to determine their effects on odontoblasts. In vivo analyses were completed following the insertion of agarose beads containing LRAP or LRAP 8, 9 into exposed cavity preparations of rat molars. After 8, 15 or 30 days' exposure, the pulp tissues were analyzed for changes in histomorphometry and cell proliferation by PCNA stainings. In vitro analyses included the effects of the addition of the recombinant proteins or peptide on cell proliferation, differentiation and adhesion of postnatal human dental pulp cells (DPCs). These studies showed that in vivo LRAP 8, 9 enhanced the reparative dentin formation as compared to LRAP. In vitro LRAP 8, 9 promoted DPC proliferation and differentiation to a greater extent than LRAP. These data suggest that amelogenin exons 8 and 9 may be useful in amelogenin-mediated pulp repair. PMID- 22301469 TI - Mining administrative health databases to advance medical science: geographical considerations and untapped potential in Canada. PMID- 22301470 TI - Photoinduced electron transfer between a donor and an acceptor separated by a capsular wall. AB - The efficient photoinduced electron transfer from a stilbene derivative incarcerated within a negatively charged organic nanocapsule to positively charged acceptors (methyl viologen and a pyridinium salt) adsorbed outside and the back electron transfer were controlled by supramolecular effects. PMID- 22301472 TI - 13-valent pneumococcal conjugate vaccine given with meningococcal C-tetanus toxoid conjugate and other routine pediatric vaccinations: immunogenicity and safety. AB - BACKGROUND: As multiple vaccines are administered concomitantly during routine pediatric immunizations, it is important to ascertain the potential interference of any new vaccine on the immune response to the concomitantly administered vaccines. Immune responses to meningococcal serogroup C-tetanus toxoid conjugate vaccine (MnCC-TT) and the diphtheria and tetanus antigens in routine pediatric vaccines (diphtheria, tetanus, acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenza type b [DTaP-HBV-IPV/Hib] and DTaP-IPV+Hib) when given concomitantly with the 13-valent pneumococcal conjugate vaccine (PCV13) were compared with responses when given with PCV7. In addition, the immunogenicity and safety of PCV13 were assessed. METHODS: Healthy infants were randomized to receive PCV13 or PCV7 (ages 2, 4, 6 and 15 months), concomitant with MnCC-TT (2, 4 and 15 months), DTaP-HBV-IPV/Hib (2, 4 and 6 months), and DTaP IPV+Hib (15 months). RESULTS: Immune responses to MnCC-TT and to the diphtheria and tetanus antigens administered with PCV13 were noninferior to the responses observed when the vaccines were administered with PCV7; >=96.6 (postinfant) and >=99.4% (posttoddler) subjects achieved prespecified immune response levels to each antigen in each group. After the infant series, >=93.0% of subjects receiving PCV13 achieved pneumococcal anticapsular immunoglobulin G concentrations >=0.35 ug/mL for all serotypes except serotype 3 (86.2%), increasing to 98.1-100% for most serotypes (serotype 3: 93.6%) after the toddler dose. Local and systemic reactions were similar between groups. CONCLUSIONS: Immune responses to MnCC-TT, and other childhood vaccines (DTaP-HBV-IPV/Hib, DTaP IPV+Hib) were noninferior when concomitantly administered with PCV13 compared with PCV7. PCV13 does not interfere with MnCC-TT. PCV13 is highly immunogenic with a favorable safety profile. PMID- 22301473 TI - In vitro studies of toxic shock toxin-1-secreting Staphylococcus aureus and implications for burn care in children. AB - BACKGROUND: The main etiologic agent of toxic shock syndrome is the toxic shock syndrome toxin-1 (TSST-1) protein secreted by Staphylococcus aureus. Diagnosis of toxic shock syndrome is difficult and is significantly underdiagnosed in young children with burns due to the nonspecific presentation coupled with a rapid deterioration in patient condition. METHODS: The lytic and cytolytic activity of a number of clinical and laboratory TSST-1-positive strains of methicillin susceptible S. aureus (101, 253, 279 and RN4282, respectively) and Pseudomonas aeruginosa PAO1 strain were tested in vitro using an assay designed to assess the relative exotoxin activity of bacteria using phospholipid vesicles and a T cell toxicity assay. In addition, the activity of lytic exotoxins such as delta -toxin and the secretion of nonlytic TSST-1 toxin from S. aureus was measured using the vesicle assay and Western blotting over the 20-hour growth of TSST-1-positive S. aureus culture. RESULTS: Both the vesicle and T cell assays suggest a lytic exotoxin-mediated mechanism of vesicle rupture and T cell death, with high levels of vesicle lysis and T cell toxicity. It is important to note that the clinical TSST-1-positive methicillin-susceptible S. aureus strains exhibited lytic exotoxin production as well as TSST-1 expression as confirmed by Western blot. CONCLUSION: We suggest that there is no correlation between the expression of TSST-1 and lack of exotoxin production. We also suggest that apurulence in an S. aureus-infected burn wound in a child should not be used to rule out toxic shock syndrome. PMID- 22301474 TI - Bartonella vinsonii endocarditis in an adolescent with congenital heart disease. AB - We report the second human case of Bartonella vinsonii subsp. berkhoffii endocarditis in a 19-year-old male with congenital heart disease. Diagnosis was established by Bartonella antibodies detected by immunofluorescence, and polymerase chain reaction amplification and sequencing from blood. PMID- 22301475 TI - Differential diagnosis of Chikungunya, dengue viral infection and other acute febrile illnesses in children. AB - BACKGROUND: Clinical manifestations of chikungunya (CHIK) are similar to those of dengue. It would be useful to be able to identify clinical manifestations that could reliably help to differentiate CHIK from dengue and other acute febrile illnesses during a CHIK outbreak in a dengue-endemic area. METHODS: A prospective cohort study was conducted between April and July 2009 in children aged 1 month to 15 years who lived in a CHIK outbreak area in southern Thailand and who had fever <7 days with arthralgia/arthritis, myalgia or rash. CHIK was confirmed by real-time polymerase chain reaction or the indirect immunofluorescence test. RESULTS: Fifty patients were suspected of having CHIK, of whom 32 were confirmed, 1 had coinfection with dengue viral infection (DVI), 10 had dengue alone and 7 had an acute febrile illness. The specificity and positive predictive value of fever and arthralgia together to diagnose CHIK were 47.1% and 74.2%, and the corresponding values of the standard clinical triad (fever, arthralgia, rash) were 70.6% and 83.3%, respectively. Fever <= 2 days, skin rash during fever and white blood cell count >= 5000 cells/mm(3) were independently and significantly associated with CHIK in comparison with DVI and acute febrile illnesses, with relative risk ratios (95% confidence intervals) of 10.4 (0.9-116) and 13.7 (1.3 145), 13.8 (1.2-164) and 14.8 (1.6-168), and 18.3 (1.7-194) and 1.8 (0.1-20.6), respectively. CONCLUSIONS: During a CHIK outbreak in a DVI-endemic area, overdiagnosis of CHIK was common. Skin rash during fever and white blood cell count >= 5000 cells/mm(3) or specific antigen testing (if available) can be helpful in differentiating CHIK from DVI. PMID- 22301476 TI - Immunogenicity, safety and reactogenicity of a mammalian cell-culture-derived influenza vaccine in healthy children and adolescents three to seventeen years of age. AB - BACKGROUND: The safety and immunogenicity of the cell-culture-derived seasonal trivalent influenza vaccine ([CCIV]; Optaflu) has been reported previously in adults and the elderly. In this study, we compared the safety, reactogenicity and immunogenicity of CCIV with a conventional egg-derived trivalent influenza vaccine (TIV) in a healthy pediatric population. METHODS: A total of 3604 subjects were randomized to receive 2 doses of CCIV or TIV (3-8 years, n = 2630) at a 28-day interval or a single vaccination (9-17 years, n = 974). Antibody levels on days 1, 29 and 50 were measured by hemaglutination inhibition assay using egg-derived and cell-derived test antigens. Adverse reactions were solicited via memory aids for 7 days after each injection, and unsolicited adverse events/serious adverse events were collected for 6 months postvaccination. RESULTS: Noninferiority of CCIV versus TIV was demonstrated for most immunogenicity measures, particularly by using cell-derived antigen in the hemaglutination inhibition assay. In 3- to 8-year-olds (the primary objective), both CCIV and TIV met all 3 Committee for Medicinal Products for Human Use immunogenicity criteria for A/H1N1 and A/H3N2 strains. Lower immune responses were observed against the B strain, fulfilling Committee for Medicinal Products for Human Use criteria only for geometric mean ratio (TIV, CCIV) and seroconversion rate (TIV, CCIV [cell-derived antigen]). Both CCIV and TIV were safe and well tolerated, with no differences in local and systemic solicited reactions or in unsolicited adverse events/serious adverse events. CONCLUSION: CCIV produced in mammalian cell culture is a safe, well-tolerated and immunogenic alternative to conventional egg-derived influenza vaccines for children and adolescents. PMID- 22301477 TI - A randomized study of tenofovir disoproxil fumarate in treatment-experienced HIV 1 infected adolescents. AB - BACKGROUND: There are few data on the safety and antiviral activity of tenofovir disoproxil fumarate (TDF) in HIV-1 infected adolescents. METHODS: A randomized, double-blinded, placebo-controlled study was conducted. Ninety adolescents (12 to <18 years) who were viremic while receiving antiretroviral treatment were randomized to receive TDF 300 mg (mean, 216.8 mg/m(2)) or placebo in combination with an optimized background regimen (OBR) for 48 weeks. The primary efficacy endpoint was time-weighted average change in plasma HIV-1 RNA from baseline at week 24 RESULTS: Eighty-seven subjects (45 TDF, 42 placebo) received the study drug. Through week 24, the median time-weighted average change in plasma HIV-1 RNA was not different between the TDF and placebo groups (-1.6 versus -1.6 log(10)copies/mL, P = 0.55). The percentages of subjects who achieved HIV-1 RNA <400 copies/mL were similar at week 24 (40.9 versus 41.5%). One fourth of subjects in the TDF and placebo groups (24.4 versus 28.6%) had at least 3 active agents in the OBR. Many subjects in both groups had baseline genotypic resistance to TDF (48.9 versus 33.3%). TDF was generally safe and well tolerated. There were no statistically significant differences in changes of renal function and bone mineral density between the 2 groups. CONCLUSION: This study of TDF in combination with an OBR in antiretroviral-experienced adolescents did not meet its primary or secondary efficacy endpoints. The effectiveness of the OBR and baseline genotypic resistance to TDF in both groups may have confounded the efficacy findings. No clinically relevant TDF-related renal or bone toxicities were observed in this adolescent population. PMID- 22301478 TI - Pharmacokinetics of micafungin in pediatric patients with invasive candidiasis and candidemia. AB - Although micafungin pharmacokinetic values were comparable between younger (<5 years) and older children (>=5 years) with candidemia and invasive candidiasis, younger children had a lower peak plasma micafungin concentration, lower micafungin exposure and larger micafungin clearance. Half-life remained unchanged with repeated dosing. Metabolite plasma concentrations remained low in older children; however, metabolite M-5 concentrations were higher in younger children. PMID- 22301479 TI - Therapeutic monitoring of voriconazole in children less than three years of age: a case report and summary of voriconazole concentrations for ten children. AB - Voriconazole is the treatment of choice for invasive aspergillosis and its use is increasing in pediatrics. Minimal pharmacokinetic data exist in young children. We report voriconazole concentrations for 10 children <3 years of age and pharmacokinetic parameters for 1 infant who had therapeutic drug monitoring performed. Trough concentrations were unpredictable based on dose, highlighting the need to follow values during therapy. PMID- 22301480 TI - When co-colonizing the nasopharynx haemophilus influenzae predominates over Streptococcus pneumoniae except serotype 19A strains to cause acute otitis media. AB - Of 368 acute otitis media (AOM) cases among 7-valent pneumococcal conjugate vaccinated children, 43.5% were colonized by multiple otopathogens in the nasopharynx but only 7.1% experienced polymicrobial AOM. When co-colonization occurred, Haemophilus influenzae predominated over all Streptococcus pneumoniae strains except 19A strains to cause AOM. Haemophilus influenzae and Streptococcus pneumoniae both predominated over Moraxella catarrhalis to cause AOM. PMID- 22301481 TI - Apophysomyces trapeziformis infection associated with a tornado-related injury. AB - This report defines the role of Apophysomyces as an aggressive fungal pathogen seen after a tornado injury. Clinical and laboratory manifestations of infections after environmentally contaminated wounds incurred during a tornado are outlined, emphasizing mechanism of injury, comorbidities, and diagnostic and treatment challenges. Therapy with systemic antifungal therapy and aggressive serial tissue debridement was successful in achieving cure. PMID- 22301482 TI - Predictive factors of low risk for bacteremia in infants with urinary tract infection. AB - We studied 140 febrile infants between 30 and 90 days of age who had a positive urine culture to analyze the risk for complications. Patients with a healthy appearance and C-reactive protein blood value less than 40 mg/L had a very small probability of complications. PMID- 22301483 TI - Commentary: procalcitonin to detect invasive bacterial infection in febrile infants. PMID- 22301484 TI - Neurologic symptoms and diarrhea in a 15-year-old boy. PMID- 22301485 TI - Group A streptococcus ventriculoperitoneal shunt infection in a child. PMID- 22301486 TI - High-order Ho multipoles in HoB2C2 observed with soft resonant x-ray diffraction. AB - Soft resonant x-ray Bragg diffraction (SRXD) at the Ho M4,5 edges has been used to study Ho 4f multipoles in the combined magnetic and orbitally ordered phase of HoB2C2. A full description of the energy dependence for both sigma and pi incident x-rays at two different azimuthal angles, as well as the ratio I(sigma)/I(pi) as a function of azimuthal angle for a selection of energies, allows a determination of the higher order multipole moments of rank 1 (dipole) to 6 (hexacontatetrapole). The Ho 4f multipole moments have been estimated, indicating a dominant hexadecapole (rank 4) order with an almost negligible influence from either the dipole or the octupole magnetic terms. The analysis incorporates both the intra-atomic magnetic and quadrupolar interactions between the 3d core and 4f valence shells as well as the interference of contributions to the scattering that behave differently under time reversal. Comparison of SRXD, neutron diffraction and non-resonant x-ray diffraction shows that the magnetic and quadrupolar order parameters are distinct. The (001/2) component of the magnetic order exhibits a Brillouin type increase below the orbital ordering temperature T(Q), while the quadrupolar order increases more sharply. We conclude that the quadrupolar interaction is strong, but quadrupolar order only occurs when the magnetic order gives rise to a quasi-doublet ground state, which results in a lock-in of the orbitals at T(Q). PMID- 22301487 TI - A chromenoquinoline-based fluorescent off-on thiol probe for bioimaging. AB - A new chromenoquinoline-based fluorescent off-on thiol probe 2 is reported. In aqueous buffer solutions at physiological pH, the probe exhibited 223-fold enhancement in fluorescence intensity by a Michael addition of cysteine to the maleimide appended to a chromenoquinoline. Cell permeability and live cell imaging of thiols are also demonstrated. PMID- 22301488 TI - Peculiarities in cases of spina bifida cystica managed recently in south-east Nigeria: could antimalarial drugs be a major but unrecognized etiologic factor? AB - BACKGROUND: Spina bifida is a long-known disease arising from the incomplete fusion of the caudal neuropore in the first month of intrauterine life. It is thought to have a multifactorial etiology, the most important of which is folic acid deficiency. In evaluating its etiology, the role of antifolate agents like antimalarial drugs is rarely given a strong mention. METHODS/PATIENTS: This is a 44-month prospective study of consecutive cases of spina bifida cystica presenting to the Neurosurgery Unit of Nnamdi Azikiwe University Teaching Hospital, Nnewi, South-East Nigeria. Data collection was with a structured proforma from presentation, and collation done with Microsoft Excel broadsheet and data analysis with SPSS and chi2 test. RESULTS: A total of 41 cases of spina bifida were attended to within the period, with 92.7% cases of spina bifida cystica. Most presented by >12-24 months, with a consistent history of maternal ingestion of antimalarial drugs during the first trimester of pregnancy. CONCLUSION: Spina bifida cystica was diagnosed mostly in children whose mothers ingested antimalarial drugs during the first trimester of gestation. There may be a need to critically evaluate the contribution of antimalarial drugs to the etiopathogenesis of this malformation and develop safer antimalarial treatment in pregnancy. PMID- 22301489 TI - Primary pediatric skull tumors. AB - BACKGROUND/AIMS: To review the pathological distribution of pediatric primary skull tumors, and to determine the diagnostic value of lesion location, patient age and lesion size. METHODS: A retrospective chart review identified 51 consecutive pediatric patients with 54 primary skull tumors, treated between 2005 and 2010. RESULTS: The most common diagnoses were dermoid cysts (n = 34) and fibrous dysplasia (n = 5). While dermoid tumors could reside anywhere (sensitivity = 0.41), a midline lesion had a specificity of 0.9 and a positive predictive value of 0.88. All of the fibrous dysplasia lesions were laterally placed, with a negative predictive value (NPV) of 1. Patient age < or >5 years had a high sensitivity and NPV for dermoid cysts and fibrous dysplasia, respectively. Size appeared to be sensitive (0.91, 0.8), but not specific (0.6, 0.78), with good NPV (0.8, 0.97) when considering dermoid cysts (<=2 cm) or fibrous dysplasia (>2 cm), respectively. CONCLUSION: Dermoid cysts followed by fibrous dysplasia are the most common primary skull tumors. Lesion location, patient age and lesion size give important clues as to the diagnosis. For the majority of cases, a clinical diagnosis based on CT is sufficient for presurgical evaluation. PMID- 22301490 TI - Unusual Resolution of a depressed skull fracture following repeat head trauma: the two-hit hypothesis? AB - An infant sustained a significant depressed skull fracture from a fall. Before the planned surgical repair of the fracture could be carried out, the child sustained a second fall that led to the complete resolution of the depressed fracture. Mechanisms to explain this unusual phenomenon are discussed. PMID- 22301491 TI - HPV-associated neuroendocrine carcinoma of the oropharynx: a rare new entity with potentially aggressive clinical behavior. AB - High-grade neuroendocrine carcinoma of the head and neck is an aggressive neoplasm which rarely arises in the oropharynx. Here we report a series of 8 oropharyngeal neuroendocrine carcinomas associated with both human papillomavirus (HPV) infection and tobacco exposure. The tumor occurred predominantly in male patients (6 of 8) at a mean age of 59 years. Histologically, these cases were all classified as poorly differentiated neuroendocrine carcinoma (small cell carcinoma) with high mitotic activity [mean 53.3 mitoses per 10 HPF], necrosis, high nuclear-to-cytoplasmic ratio, and nuclear molding. One case also exhibited a moderately differentiated component, and one other case had a component of squamous cell carcinoma with basaloid features. Neuroendocrine differentiation was confirmed by immunoreactivity for synaptophysin and/or chromogranin A in all cases. P63 staining was negative, except in 1 case. Seven of the 8 cases showed strong and diffuse p16 expression, a surrogate marker for high-risk HPV infection. HPV infection was confirmed in 6 of these 7 cases by HPV in situ hybridization and/or polymerase chain reaction analysis. HPV subtypes 16, 18, and 33 were identified in 1 case each by polymerase chain reaction testing. Six of the 7 patients for whom clinical history was available presented with advanced disease (4 with regional lymph node metastases, 1 with distant metastases, and 1 with distant and locoregional metastases). Disease recurred in 5 of the 6 patients with available clinical follow-up, with 3 developing distant metastases to brain, bones, lung, pleura, adrenal glands, and pancreas. These 3 cases were all from the HPV-positive group. In summary, neuroendocrine carcinoma of the oropharynx represents a rare novel HPV-associated entity with high-grade histologic features and aggressive clinical behavior. PMID- 22301492 TI - Use of mismatch repair immunohistochemistry and microsatellite instability testing: exploring Canadian practices. AB - BACKGROUND: The mismatch repair (MMR) status of tumors is being increasingly recognized as a prognostic, predictive, and possible germline predisposition/Lynch syndrome (LS) biomarker in colorectal cancer and other cancer types, particularly in endometrial cancer. Current methods (clinical history and tumor morphology) to predict MMR deficiency (dMMR) are suboptimal, and implementation of reflex laboratory testing of appropriate tumors has been recommended, a strategy requiring test standardization and clinical coordination. METHODS: Two web-based questionnaires were administered, a general and a specialist laboratory questionnaire, to establish the availability of such tests, requisite clinical/pathology integration, current mode of test initiation, reporting and recommendation practices, and education and attitudes among pathologists. Technical aspects were reviewed on the basis of specialist laboratory practice. RESULTS: Of 76 respondents, 21.5% were unaware or were uncertain whether they had access to MMR immunohistochemistry. Although 78.9% of respondents had access to such testing, an integrated approach to the identification of patients with LS is lacking, being limited to just 9 centers. The majority (70%) of testing is clinician initiated, with variable implementation of reflex testing and divergent practices in recommendation to test. Standardized reporting is lacking in many centers. Education on MMR in endometrial cancer is poor compared with that in colorectal cancer (P<0.0001). INTERPRETATION: This multicenter questionnaire highlights heterogenous practices in dMMR testing and LS identification, both in clinical terms and with regard to technical aspects of testing. An integrated multidisciplinary approach is lacking, and there is a need to educate physicians and resolve ethical issues. A Canadian consensus statement and national guidelines on dMMR testing are urgently needed, requiring input from pathologists, clinicians, and genetic counselors. PMID- 22301493 TI - Urachal carcinomas of the nonglandular type: salient features and considerations in pathologic diagnosis. AB - The vast majority of malignant urachal epithelial tumors have a glandular morphology (ie, adenocarcinoma), to which our principal understanding of urachal carcinoma and its prevailing set of diagnostic criteria are largely ascribed. The 2004 World Health Organization classification of genitourinary tumors recognizes other rarer histologic types of urachal carcinomas such as urothelial, squamous cell, and other carcinomas. However, the clinicopathologic data for these nonglandular groups of urachal carcinomas are very limited, being detailed only in sporadic case reports. Some of the criteria recommended for pathologic confirmation of urachal carcinomas were formulated almost exclusively for urachal adenocarcinoma and may not be relevant or applicable for nonglandular tumors. Here, we present 7 examples of pure (5) and mixed predominant (2) nonglandular urachal carcinomas. Patients were 45 to 85 years of age (mean, 64.1) with a male predominance (male-to-female ratio=6:1). Six tumors were related to the bladder [dome (3) or dome/supravesical (3)] and 1 was entirely supravesical. Histologically, 5 were urothelial carcinomas, of pure or mixed histology, all were high grade and invasive, and 2 were small cell carcinomas. Two urothelial carcinomas had focal (<5%) glandular differentiation and signet ring cell change, and 1 had admixed focal malignant squamous cells and high-grade dedifferentiated components. Four of 5 urachal urothelial carcinomas exhibited solid and partly cavitary or luminal growth with papillary structures and a variable amount of necrosis within the cavity. The 2 small cell carcinomas were pure, had classic undifferentiated neuroendocrine histology, were situated at the bladder dome, and were partly cavitary filled with necrotic debris. Urachal remnant was identified in 6 tumors mainly with dysplastic transitional cells in the urachal canal or rudimentary nests and tubules. All 6 bladder-related urachal tumors exhibited reverse invasive front from the surface, including 2 tumors that ulcerated the bladder mucosa. One tumor had concomitant in situ and noninvasive high-grade papillary urothelial carcinomas in the main bladder lumen. Sheldon stages at presentation were IIIA (2), IVA (3), and IVB (2). Follow-up in all 7 cases (<1 to 60 mo; median, 12.5 mo) showed that 6 patients had died of disease, including the 2 patients with small cell carcinoma. In conclusion, nonglandular urachal carcinoma may occur with pure histology or admixed with high-grade dedifferentiated morphologies and a minor adenocarcinoma component. These tumors may arise as deep-seated bladder-related or completely supravesical tumors along the urachal tract and may exhibit reverse invasive spread toward the bladder surface. Cavitary or luminal growth may occur that could be attributed to the intraurachal neoplastic proliferation. Urachal urothelial carcinomas in particular may contain papillary structures within the tumor and urachal cavity. Concomitant primary urothelial carcinoma outside of the urachus and tumor extension to bladder mucosa may occur, which should not negate diagnosis of an urachal primary. Behavior appears poor, as most tumors present with higher stage. PMID- 22301494 TI - Infarct-like necrosis: a distinct form of necrosis seen in colorectal carcinoma liver metastases treated with perioperative chemotherapy. AB - The response of colorectal adenocarcinoma liver metastases to perioperative chemotherapy can be assessed histologically in partial hepatectomy specimens. Necrosis in this scenario may represent a lack of treatment effect or a therapeutic response to chemotherapy. This study sought to validate the histologic classification of necrosis into 2 types: usual necrosis (UN) representing an absence of treatment effect, and infarct-like necrosis (ILN) representing a therapeutic response to chemotherapy. Tumor regression grade (TRG) is a previously described prognosticating method that estimates tumor replacement by fibrosis. We incorporated ILN into a modified TRG (mTRG) and compared its performance as a prognostic factor against TRG. A retrospective clinical and histologic review was undertaken of all partial hepatectomies performed for colorectal liver metastases at our center between 2004 and 2010. Clinicopathologic features were compared between the 2 types of necrosis, including survival stratified by TRG and mTRG. A total of 109 cases were reviewed, with 46 patients receiving perioperative chemotherapy. ILN was identified in 12 cases, and all of these cases were associated with perioperative chemotherapy. ILN was significantly associated with perioperative treatment with bevacizumab. In patients receiving perioperative chemotherapy, those with ILN had superior disease-free survival compared with those with UN (P=0.047). mTRG1 to 2 scores were associated with significantly better survival compared with mTRG3 to 5 scores. In contrast, use of TRG did not demonstrate a significant difference in disease-free and overall survival. ILN represents a form of treatment effect and should be distinguished from UN. A modified grading system that incorporates ILN may enhance the prognostic utility of TRG. PMID- 22301495 TI - Gamma heavy-chain disease: defining the spectrum of associated lymphoproliferative disorders through analysis of 13 cases. AB - Gamma heavy-chain disease (gHCD) is defined as a lymphoplasmacytic neoplasm that produces an abnormally truncated immunoglobulin gamma heavy-chain protein that lacks associated light chains. There is scant information in the literature regarding the morphologic findings in this rare disorder, but cases have often been reported to resemble lymphoplasmacytic lymphoma (LPL). To clarify the spectrum of lymphoproliferative disorders that may be associated with gHCD, this study reports the clinical, morphologic, and phenotypic findings in 13 cases of gHCD involving lymph nodes (n=7), spleen (n=2), bone marrow (n=8), or other extranodal tissue biopsies (n=3). Clinically, patients showed a female predominance (85%) with frequent occurrence of autoimmune disease (69%). Histologically, 8 cases (61%) contained a morphologically similar neoplasm of small lymphocytes, plasmacytoid lymphocytes, and plasma cells that was difficult to classify with certainty, whereas the remaining 5 cases (39%) showed the typical features of one of several other well-defined entities in the 2008 WHO classification. This report demonstrates that gHCD is associated with a variety of underlying lymphoproliferative disorders but most often shows features that overlap with cases previously reported as "vaguely nodular, polymorphous" LPL. These findings also provide practical guidance for the routine evaluation of small B-cell neoplasms with plasmacytic differentiation that could represent a heavy-chain disease and give suggestions for an improved approach to the WHO classification of gHCD. PMID- 22301496 TI - Tumor invasion of muscular vessels predicts poor prognosis in patients with pancreatic ductal adenocarcinoma who have received neoadjuvant therapy and pancreaticoduodenectomy. AB - Lymphovascular invasion (LVI) is a prognostic factor in many types of human malignancies, including pancreatic ductal adenocarcinoma (PDAC). However, the prognostic significance of LVI in patients with PDAC who have received neoadjuvant therapy and pancreaticoduodenectomy is unclear. In this study, we analyzed LVI in 212 patients who had received neoadjuvant chemoradiation and subsequent pancreaticoduodenectomy at our institution between January 1999 and December 2007. LVI was present in 61.8% (131/212) of the patients. Of the 131 patients who were positive for LVI, 67 (31.6%) had tumor invasion into lymphovascular spaces without muscle layer (nonmuscular lymphovascular spaces), and 64 (30.2%) had tumor invasion into muscular vessels. Tumor invasion into muscular vessels correlated with higher frequencies of positive resection margin, lymph node metastasis, and locoregional/distant recurrence. Patients with tumor invasion into muscular vessels had significantly shorter disease-free survival and overall survival than did patients who had no LVI or who had tumor invasion of nonmuscular lymphovascular spaces (P<0.01). Tumor invasion into muscular vessels is an independent prognostic factor in patients with PDAC who have received neoadjuvant therapies. Our results showed that tumor invasion into muscular vessels plays an important role in the progression of PDAC and in predicting prognosis in this group of patients. PMID- 22301498 TI - Diagnostic utility of p16, CDK4, and MDM2 as an immunohistochemical panel in distinguishing well-differentiated and dedifferentiated liposarcomas from other adipocytic tumors. AB - Adipocytic tumors are the most common type of soft tissue neoplasms. Distinguishing atypical lipomatous tumor-well-differentiated liposarcoma (WDL) from benign adipocytic neoplasms and dedifferentiated liposarcoma (DDL) from pleomorphic or myxoid liposarcoma (LPS) can be difficult. WDL and DDL characteristically harbor amplifications of the MDM2 and CDK4 cell cycle oncogenes with protein overexpression and can also overexpress the cell cycle regulator p16. We assessed the utility of immunohistochemistry for CDK4, MDM2, and p16 in the routine histopathologic diagnosis of WDL/DDL from other adipocytic tumors. Immunohistochemistry for the trio of markers was performed on 216 adipocytic neoplasms (31 WDLs, 57 DDLs, 11 myxoid LPS, 2 pleomorphic LPS, 91 lipomas (including intramuscular, fibro, angio, and ossifying subtypes), 18 spindle/pleomorphic lipomas, and 6 hibernomas. Sixty-eight percent of WDLs and 72% of DDLs expressed all 3 antigens, whereas 100% of WDLs and 93% of DDLs expressed at least 2 antigens. The sensitivity and specificity of the trio for detecting WDLs/DDLs were 71% and 98%, respectively. The sensitivity and specificity of CDK4 for detecting WDLs/DDLs were 86% and 89%, those of MDM2 were 86% and 74%, and those of p16 were 93% and 92%, respectively. The immunohistochemical trio of CDK4, MDM2, and p16 is a useful ancillary diagnostic tool that provides strong support in distinguishing WDLs and DDLs from other adipocytic neoplasms and is potentially more sensitive than previously assessed combinations of CDK4 and MDM2. p16 was the most sensitive and specific marker for detecting WDL/DDL, and the combination of CDK4 and p16 is of more discriminatory value than the combination of either with MDM2, the least sensitive and specific of the 3 markers. PMID- 22301497 TI - Perineural and intraneural invasion in posttherapy pancreaticoduodenectomy specimens predicts poor prognosis in patients with pancreatic ductal adenocarcinoma. AB - Perineural invasion (PNI) is one of the established prognostic factors in pancreatic ductal adenocarcinoma (PDAC). However, the prognostic significance of PNI in patients with PDAC who received neoadjuvant therapy and pancreaticoduodenectomy is not clear. In this study, we performed a detailed examination of neural invasion in pancreaticoduodenectomy specimens from 212 patients with PDAC who received neoadjuvant chemoradiation (treated group) and in 60 untreated patients at our institution between January 1999 and December 2007. The frequency of PNI was higher in the untreated group (80%, 48/60) than in the treated group (58%, 123/212). For the 123 treated cases that were positive for PNI, extratumoral PNI, intratumoral PNI, intrapancreatic PNI only, extrapancreatic PNI, and intraneural invasion were identified in 86 (69.9%), 37 (30.1%), 11 (8.9%), 112 (91.1%), and 35 cases (28.5%), respectively. The presence of PNI correlated with tumor size, margin status, lymph node metastasis, pathologic tumor, and American Joint Committee on Cancer stages in the treated group. Tumor involvement of nerves >0.8 mm correlated with higher frequency of positive margin compared with tumors with PNI involving nerves <=0.8 mm but not with other clinicopathologic parameters and survival. In the treated group, the presence of PNI or intraneural invasion correlated significantly with shorter disease-free survival and overall survival compared with no PNI or PNI only, respectively. PNI was an independent prognostic factor for both disease-free survival and overall survival in multivariate analysis. Our results showed that PNI plays an important role in the progression of PDAC and in predicting prognosis in this group of patients. PMID- 22301499 TI - Expression of OCT3/4 in renal medullary carcinoma represents a potential diagnostic pitfall. AB - Renal medullary carcinoma (RMC) is a rare aggressive renal tumor that classically afflicts young black patients with sickle cell trait. The tumor shows overlapping pathologic and clinical characteristics with collecting duct carcinoma and urothelial carcinoma, which often results in a diagnostic conundrum. When the tumor presents in a metastatic site in the absence of a history of renal tumor, germ-cell tumor is often a primary diagnostic consideration, given the young age of most patients. OCT3/4 is an immunohistochemical marker that is routinely used in clinical practice and is widely considered to be a specific marker for germ cell tumor. We studied the pathologic and immunohistochemical characteristics of 14 cases of RMC. Immunohistochemical staining for OCT3/4 staining was noted in 10/14 RMCs with strong nuclear staining in 8 cases and was absent in all cases of collecting duct carcinoma and urothelial carcinoma. OCT3/4 expression is not specific to germ-cell tumor and is seen in the majority of RMC cases. Caution must be exercised in interpreting the presence of OCT3/4 staining in a poorly differentiated neoplasm, especially at a metastatic site as a germ-cell tumor, as this may represent a potential diagnostic pitfall. PMID- 22301500 TI - NUT midline carcinoma: report of 2 cases suggestive of pulmonary origin. AB - In this study, we report 2 pediatric cases of nuclear protein of the testis (NUT) midline carcinoma (NMC) suggestive of pulmonary origin: case 1 was a 14-year-old Japanese boy and case 2 was a 7-year-old Japanese girl. Initial symptoms of both cases were prolonged cough and chest pain, and the case 2 patient also complained of lumbago and lumbar mass due to bone metastases. Imaging studies revealed that pulmonary tumors from both patients were located at the hilar region of the lower lobe. Biopsies of the tumors showed undifferentiated carcinoma in case 1 and combined undifferentiated and squamous cell carcinoma in case 2. Despite intensive treatment with chemotherapy and radiation, progression of neither tumor was controlled, and both patients died of the tumors at 1 year (case 1) and 4 months (case 2) after onset of disease. Both tumors were diffusely positive for p63 and NUT expression and were partially positive for various cytokeratins. Reverse transcription polymerase chain reaction analysis and subsequent direct sequencing revealed that the bromodomain-containing protein 4-NUT chimeric gene was present in tumor tissue of both patients, leading to a diagnosis of NMC. The tumor cells of case 1 were also positive for thyroid transcription factor-1 expression, but those of case 2 were negative. Histologic examination of the surgically removed lung tumor of case 1 indicated that the origin of the tumor was basal cells of the bronchiolar epithelia. PMID- 22301501 TI - MDM2 and CDK4 immunohistochemical coexpression in high-grade osteosarcoma: correlation with a dedifferentiated subtype. AB - Low-grade osteosarcomas comprise a distinct subset of osteosarcomas. They may occasionally dedifferentiate into high-grade tumors, typically in the form of high-grade osteosarcoma, which are histologically indistinguishable from conventional osteosarcomas. MDM2 and CDK4 are often amplified in low-grade osteosarcomas and their dedifferentiated counterparts, and the encoded proteins are accordingly overexpressed. As MDM2/CDK4 expression was reportedly rare in conventional osteosarcoma, we hypothesized that these markers may help separate dedifferentiated osteosarcoma from the conventional type. To test this, we performed MDM2 and CDK4 immunohistochemistry on 81 primary and 26 recurrent/metastatic high-grade osteosarcomas and correlated these data with the histology of the primary resection material, with particular attention to the potential presence of any coexisting low-grade osteosarcomatous components. MDM2 and CDK4 coexpression was identified in 7 cases, and on careful histologic review 6 of them were discovered to contain foci of coexisting low-grade elements. One case was a known dedifferentiated parosteal osteosarcoma, and the remaining 5 cases were newly identified dedifferentiated osteosarcomas in which the limited low-grade components were originally unrecognized. An additional 11 cases expressed either marker alone, whereas the remaining 89 cases were negative for both markers; no resection material from these 100 cases presented with a low grade component. MDM2/CDK4 gene amplification status, determined by quantitative polymerase chain reaction in selected cases, was largely concordant with immunoexpression. Our data suggest that MDM2 and CDK4 coexpression in high-grade osteosarcomas is sensitive and specific to those that progressed from low-grade osteosarcomas, and immunohistochemistry may help identify this dedifferentiated subgroup to facilitate accurate subclassification. PMID- 22301502 TI - Low-grade sinonasal sarcoma with neural and myogenic features: a clinicopathologic analysis of 28 cases. AB - Sarcomas of the sinonasal region are rare. We describe a distinct spindle cell sarcoma of the sinonasal region characterized by concomitant neural and myogenic differentiation. Consultation files and surgical cases from Mayo Clinic were reviewed. Twenty-eight cases were identified that met the inclusion criteria. Clinical data were collected from medical records, consultation letters, and referring pathologists. Reverse transcriptase-polymerase chain reaction for synovial sarcoma fusion transcripts was performed on 18 cases. Cytogenetic studies were performed on 2 cases. The 21 female and 7 male patients ranged in age from 24 to 85 years (mean, 52 y). All cases showed a characteristic histology, which included a cellular spindle cell neoplasm with uniform, elongate nuclei and an infiltrative growth pattern. All tumors demonstrated expression of S-100 with actin positivity in 96% of cases tested. Reverse transcriptase polymerase chain reaction for synovial sarcoma fusion transcripts was negative in all cases tested. Cytogenetic studies conducted on 2 cases demonstrated the chromosomal translocation t(2;4). The nasal cavity (54%) and ethmoid sinus (57%) were the most commonly involved areas, singly or in combination. Follow-up information was available for 57% (16/28) of cases, with a mean of 8.3 years. Of these, 44% (7/16) experienced at least 1 recurrence. No patient has developed metastases or died of disease. We describe a unique tumor with a characteristic morphologic, immunophenotypic, and cytogenetic profile. On the basis of the locally aggressive nature of this lesion we believe it is best considered a low grade sarcoma and suggest the term low-grade sinonasal sarcoma with neural and myogenic features. PMID- 22301503 TI - The profile of acinic cell carcinoma after recognition of mammary analog secretory carcinoma. AB - To determine the influence of the newly described mammary analog secretory carcinoma (MASC) with ETV6 translocation on our understanding of salivary acinic cell carcinoma (AciCC), we reviewed 81 cases of AciCC: 64 "classic" AciCCs, 11 AciCCs with high-grade transformation (HGT), and 17 zymogen granule poor AciCCs. ETV6 fluorescence in situ hybridization revealed that classic AciCC (7 of 7 tested) and AciCC-HGT (4 of 4 tested) have intact ETV6. However, 10 of 17 zymogen granule poor AciCCs showed ETV6 translocation and were reclassified as MASC; the diagnosis of AciCC was retained for cases with intact ETV6. MASCs were distinguished by the lack of zymogen granules, mucin production, and stronger S100 reactivity. MASC showed a striking male predilection (male-to-female ratio, 8:2) in contrast to AciCC (male-to-female ratio, 1:1.5; P<0.01). Compared with cases of confirmed AciCC, AciCC-HGT occurred in older patients (mean age of 66.2 y vs. 47.7 y, P=0.007) and showed a poorer mean overall survival [40.2 mo (95% confidence interval (CI), 7.5-73 mo) vs. 125 mo (95% CI: 98-151 mo); P<0.001]. Patients with confirmed AciCC without HGT showed a recurrence rate of 15% (9/60) and a 7.9% (3/38) incidence of regional lymph node involvement. It appears that more than half of zymogen granule poor AciCCs are likely to represent MASC. Even after excluding cases of MASC, the presence of HGT in AciCC predicts poorer overall survival. PMID- 22301504 TI - Angiofibroma of soft tissue: clinicopathologic characterization of a distinctive benign fibrovascular neoplasm in a series of 37 cases. AB - Thirty-seven cases of a distinctive benign fibrovascular soft tissue tumor that may be mistaken for a low-grade sarcoma are described. There were 25 female and 12 male patients, ranging in age from 6 to 86 years (median, 49 y). The tumors presented most commonly as a slowly growing painless mass located in the soft tissues of the extremities, mainly the lower extremity, often in relationship to joints or fibrotendinous structures. Most lesions (29 cases) were well circumscribed, ranging in size from 1.2 to 12 cm (median, 3.5 cm). The microscopic appearance was remarkably consistent and was characterized by 2 components: a relatively uniform proliferation of bland, spindle-shaped cells with inconspicuous cytoplasm and ovoid-to-tapering nuclei set in a variably collagenous or myxoid stroma and a prominent vascular network composed of numerous small, branching, thin-walled blood vessels, often accompanied by medium sized round or irregular and ectatic vessels. Mitoses (1-4/10 hpf) were occasionally observed (9 cases). Mild degenerative nuclear atypia was uncommon (5 cases). Tumor cells expressed epithelial membrane antigen at least focally in 16 of 36 cases (44%), CD34 and smooth muscle actin in 5 cases (14%), and desmin in 4 cases (11%); none expressed S100 protein. Five out of 6 cases analyzed cytogenetically showed a simple karyotype with a balanced t(5;8) chromosomal translocation. Treatment consisted of surgical resection: either simple excision (29 cases), wide excision (6 cases), or amputation (1 case). Follow-up information was available for 28 patients (range, 6 to 144 mo; mean, 51.9 mo). Most patients were alive with no evidence of disease, regardless of the status of surgical resection margins. Four patients developed local recurrence 9, 13, 36, and 120 months after the primary tumor was removed; only in 1 case was there an association with extensively positive surgical resection margins. One of these patients developed a second recurrence 2 months after the first one. None of the patients developed metastasis. The designation "angiofibroma of soft tissue" is proposed to reflect both the likely fibroblastic nature of the proliferating cells and the prominent vascularization of this benign soft tissue neoplasm. PMID- 22301505 TI - Calcium, phosphate and the risk of cardiovascular events and all-cause mortality in a population with stable coronary heart disease. AB - OBJECTIVE: High serum calcium and phosphate levels have been linked to cardiovascular diseases and all-cause mortality but evidence from longitudinal studies is scarce, especially among patients with pre-existing coronary heart disease. The association between baseline calcium and phosphate and prognosis was examined in a cohort study of patients with stable coronary heart disease. METHODS: Serum calcium and phosphate were measured in a cohort of initially 1206 patients undergoing a 3 week rehabilitation programme after an acute cardiovascular event and subsequently being followed-up for 8 years. Multivariate Cox regression was employed to assess the association of quartiles and continuous levels of calcium and phosphate with secondary cardiovascular events and all cause mortality. RESULTS: No significant risk elevations were observed for secondary cardiovascular event incidence in models adjusted for a variety of potential confounders. High calcium levels, however, were strongly associated with mortality risk in adjusted models (HR(Q4vsQ1)=2.39 (1.22 to 4.66)). In additional multivariable analyses, the calcium/albumin ratio was predictive for all-cause mortality (HR(Q4vsQ1)=2.66 (1.35 to 5.22)) and marginally predictive for cardiovascular event incidence (HR(Q4vsQ1)=1.74 (1.00 to 3.05)). CONCLUSIONS: Calcium and the ratio of calcium with albumin, its major binding protein, were strongly associated with all-cause mortality among patients with coronary heart disease. The underlying mechanisms and the clinical implications of these findings deserve further study. PMID- 22301506 TI - Bivalirudin in acute myocardial infarction: NICE guidance. PMID- 22301507 TI - TNFalpha theory for the beneficial effects of acupuncture on infantile colic: formula-fed infants and probiotic treatments. PMID- 22301508 TI - Multimodal stepped care approach with acupuncture and PPAR-alpha agonist palmitoylethanolamide in the treatment of a patient with multiple sclerosis and central neuropathic pain. AB - Central neuropathic pain is a common debilitating symptom in patients with multiple sclerosis. Side effects of analgesics often limit reaching therapeutic dosages. In this case report, a 61-year-old woman with chronic central neuropathic pain due to multiple sclerosis is described. Acupuncture could only partly and temporarily reduce the pain. However, after adding the natural compound palmitoylethanolamide, a glial modulator and peroxisome proliferator activated receptor-alpha agonist, pain reduction was more pronounced and the interval between acupuncture sessions could be increased. A multimodal stepped care approach is demonstrated, with acupuncture and palmitoylethanolamide both influencing non-neuronal cells, such as activated glial cells, which are key factors in the development and maintenance of neuropathic pain. PMID- 22301509 TI - Using the Mini-Mental State Examination to screen for delirium in elderly patients with hip fracture. AB - BACKGROUND: The main aim of this paper was to examine the usefulness of the Mini Mental State Examination (MMSE) for screening delirium in elderly patients with hip fracture. METHODS: The sample included 364 elderly patients with hip fracture admitted to two hospitals in Oslo. Delirium was assessed by the Confusion Assessment Method (CAM) as an approximation of the gold standard, DSM-IV. To evaluate the psychometric properties of the MMSE scale, we used the Mokken nonparametric latent trait model for unidimensional scaling. RESULTS: In total, 76 (21%) patients were diagnosed with delirium based on the CAM, and 141 (43%) had preexisting cognitive impairment. As a screening tool, the recommended MMSE cut-point of 24 showed an acceptable sensitivity of 88% with a specificity of 54%. The prediction of delirium, based on logistic regression on the MMSE total score and on the 5 items selected by the stepwise logistic regression procedure, gave clearly less acceptable results. CONCLUSIONS: Our study indicates that the MMSE may be useful in screening for delirium, but the high percentage of false positives shows that it does not have diagnostic potential in patients with hip fracture. PMID- 22301510 TI - Solvothermal synthesis of monodisperse nanocrystals. AB - Monodisperse nanocrystals have drawn tremendous interests in terms of their fundamental sciences and practical applications. In this review, some recent developments in the solvothermal synthesis of monodisperse nanocrystals are discussed, and we present an outlook on the field. PMID- 22301516 TI - Fe3O4/Fe/carbon composite and its application as anode material for lithium-ion batteries. AB - A plum pudding-like Fe(3)O(4)/Fe/carbon composite was synthesized by a sol-gel polymerization followed by a heat-treatment process and characterized by X-ray diffraction, Raman spectroscopic analysis, thermogravimetric analysis, scanning electron microscopy with energy-dispersive spectroscopy, transmission electron microscopy, and electrochemical test. In this composite, uniform spherical Fe(3)O(4)/Fe nanoparticles of about 100 nm were embedded into carbon matrix with high monodispersion. As-prepared Fe(3)O(4)/Fe/carbon composite electrode exhibits a stable and reversible capacity of over 600 mA h g(-1) at a current of 50 mA g( 1) between 0.002 V and 3.0 V, as well as excellent rate capability. The plum pudding-like structure, in which trace Fe promotes conductivity and carbon matrix mediates the volume change, can enhance the cycling performance and rate capability of Fe(3)O(4) electrode. This unique structure is valuable for the preparation of other electrode materials. PMID- 22301517 TI - Entecavir versus lamivudine in the treatment of chronic hepatitis B patients with hepatic decompensation. AB - BACKGROUND: Lamivudine has been widely used in chronic hepatitis B patients with hepatic decompensation, but its use is limited by drug resistance. This outcome research aimed to investigate the comparative efficacy and safety of entecavir versus lamivudine in decompensated patients. METHODS: Between November 2004 and February 2010, 126 consecutive treatment-naive patients received either entecavir (n=53) or lamivudine (n=73) for decompensated chronic hepatitis B. All patients presented with both hyperbilirubinaemia and coagulopathy. Primary outcome was mortality within 1 year; secondary outcomes included liver-related mortality, biochemical and virological response, and improvement of hepatic dysfunction. RESULTS: Both treatment groups were comparable in baseline characteristics. A total of 19 (35.8%) entecavir and 33 (45.2%) lamivudine receivers expired within 1 year, respectively (P=0.29, log rank test). Age (hazard ratio [HR] 1.04 per year, 95% CI 1.01, 1.06), cirrhosis (HR 2.07, 95% CI 1.02, 4.23), and international normalized ratio for prothrombin time (HR 1.44, 95% CI 1.20, 1.74) were independent baseline predictors for all-cause mortality. Antiviral therapy was also unrelated to liver-specific death. However, more patients taking entecavir tended to attain aminotransferase normalization (76.5% versus 52.5%; P=0.05) and viral DNA undetectability (100% versus 58.3%; P=0.06). Moreover, entecavir was associated with significantly greater reduction of the model for end-stage liver disease scores (median 10.0 versus 4.3; P=0.02). Overall, 3 (7.5%) lamivudine but no entecavir users acquired drug resistance in 1 year (P=0.25). CONCLUSIONS: Entecavir as compared with lamivudine is similar in the effect on short-term mortality but is associated with greater clinical improvement among chronic hepatitis survivors who recovered from hepatic decompensation. PMID- 22301518 TI - The correlation of maternal uric acid concentration with small-for-gestational age fetuses in normotensive pregnant women. AB - AIM: Elevated maternal serum uric acid is associated with small-for-gestational age (SGA) fetuses. We investigated whether uric acid concentrations in normotensive pregnant women are correlated with fetal growth and related to kidney function. METHODS: We carried out a case-control study using 40 patients who delivered SGA fetuses identified from the perinatal database and 80 patients who delivered appropriate-for-gestational-age (AGA) fetuses as the controls at Okayama University Hospital. Blood pressure, serum uric acid and creatinine level were measured in the patients' third trimester. RESULTS: Maternal serum uric acid (p = 0.0003) and creatinine (p < 0.0001) concentrations, as well as systolic and diastolic blood pressures (p =0.014 and 0.037, respectively), were significantly increased in the SGA group. There was a strong negative correlation between serum uric acid levels and birth weights (r = -0.59; p = 0.006) and a significant positive correlation between maternal serum uric acid and creatinine levels (r = 0.43; p < 0.05) in cases of severe SGA (<5th percentile). Multiple linear regression analysis indicated that uric acid is an independent risk factor for SGA. CONCLUSIONS: Increasing maternal uric acid concentrations were associated with slightly impaired kidney function and SGA in normotensive pregnant women. PMID- 22301519 TI - Voluntary attention modulates processing of eye-specific visual information. AB - Visual attention functions to select relevant information from a vast amount of visual input that is available for further processing. Information from the two eyes is processed separately in early stages before converging and giving rise to a coherent percept. Observers normally cannot access eye-of-origin information. In the research reported here, we demonstrated that voluntary attention can be eye-specific, modulating visual processing within a specific monocular channel. Using a modified binocular-rivalry paradigm, we found that attending to a monocular cue while remaining oblivious to its eye of origin significantly enhanced the competition strength of a stimulus presented to the cued eye, even when the stimulus was suppressed from consciousness. Furthermore, this eye specific attentional effect was insensitive to low-level properties of the cue (e.g., size and contrast) but sensitive to the attentional load. Together, these findings suggest that top-down attention can have a significant modulation effect at the eye-specific stage of visual information processing. PMID- 22301520 TI - Early conceptual and linguistic processes operate in independent channels. AB - Language and concepts are intimately linked, but how do they interact? In the study reported here, we probed the relation between conceptual and linguistic processing at the earliest processing stages. We presented observers with sequences of visual scenes lasting 200 or 250 ms per picture. Results showed that observers understood and remembered the scenes' abstract gist and, therefore, their conceptual meaning. However, observers remembered the scenes at least as well when they simultaneously performed a linguistic secondary task (i.e., reading and retaining sentences); in contrast, a nonlinguistic secondary task (equated for difficulty with the linguistic task) impaired scene recognition. Further, encoding scenes interfered with performance on the nonlinguistic task and vice versa, but scene processing and performing the linguistic task did not affect each other. At the earliest stages of conceptual processing, the extraction of meaning from visually presented linguistic stimuli and the extraction of conceptual information from the world take place in remarkably independent channels. PMID- 22301523 TI - Correlated disorder in a Kondo lattice. AB - Motivated by recent experiments on Yb-doped CeCoIn5, we study the effect of correlated disorder in a Kondo lattice. Correlations between the impurities are considered at the two-particle level. We use a mean-field theory approximation for the Anderson lattice model to calculate how the emergence of coherence in the Kondo lattice is impacted by correlations between impurities. We show that the rate at which disorder suppresses coherence temperature depends on the length of the impurity correlations. As the impurity concentration increases, we generally find that the suppression of coherence temperature is significantly reduced. The results are discussed in the context of available experimental data. PMID- 22301521 TI - Shrinking lung syndrome successfully treated with rituximab and cyclophosphamide. AB - Shrinking lung syndrome (SLS) is an uncommon feature of systemic lupus erythematosus (SLE) characterized by dyspnea, pleuritic chest pain, diaphragmatic elevation, restrictive ventilatory defect and reduced respiratory muscle strength as measured by volitional tests. We report the case of a 28-year-old woman with overlapping features of SLE and Sjogren syndrome who developed severe SLS while receiving corticosteroids and azathioprine for severe polyarthritis. She was treated with a combination of rituximab and cyclophosphamide, which led to a dramatic improvement in her clinical condition and respiratory function tests. The increase in vital capacity was one of the highest among 35 published cases of SLS. Thus, restoring a near-normal lung function is an achievable goal in SLS, and the use of rituximab, with or without concomitant cyclophosphamide, certainly deserves further study in this setting. PMID- 22301524 TI - Domestic violence screening of obstetric triage patients in a military population. AB - OBJECTIVE: The objective was to estimate the self-reported prevalence of domestic violence in a pregnant military population presenting for emergency care, and to determine the acceptability of domestic violence screening. STUDY DESIGN: A prospective observational survey of patients presenting for obstetric emergency care. Women were anonymously screened for domestic violence using the Abuse Assessment Screen. RESULT: A total of 499 surveys were distributed, with 26 duplicate surveys. After excluding the 12 blank surveys, a total of 461 surveys were included in the final analysis. The lifetime prevalence of domestic violence (including physical, emotional and sexual abuse) was 22.6% (95% CI=19.0 to 26.4) with 4.1% (95% CI=2.3-6.0) of women reporting physical abuse in the past year and 2.8% (95% CI=1.3-4.3) reporting abuse since becoming pregnant. The majority of women 91.8% (95% CI=88.7-94.2) were not offended by domestic violence screening and 88.8% (95% CI=82.0-88.9) felt that patients should be routinely screened. CONCLUSION: The self-reported prevalence of domestic violence in a pregnant military population presenting for emergency care was 22.6%. Most women are not offended by domestic violence screening and support routine screening. PMID- 22301525 TI - NIDCAP improves brain function and structure in preterm infants with severe intrauterine growth restriction. AB - OBJECTIVE: The effect of NIDCAP (Newborn Individualized Developmental Care and Assessment Program) was examined on the neurobehavioral, electrophysiological and neurostructural development of preterm infants with severe intrauterine growth restriction (IUGR). STUDY DESIGN: A total of 30 infants, 27-33 weeks gestation, were randomized to control (C; N=17) or NIDCAP/experimental (E; N=13) care. Baseline health and demographics were assessed at intake; electroencephalography (EEG) and magnetic resonance imaging (MRI) at 35 and 42 weeks postmenstrual age; and health, growth and neurobehavior at 42 weeks and 9 months corrected age (9 months). RESULTS: C and E infants were comparable in health and demographics at baseline. At follow-up, E infants were healthier, showed significantly improved brain development and better neurobehavior. Neurobehavior, EEG and MRI discriminated between C and E infants. Neurobehavior at 42 weeks correlated with EEG and MRI at 42 weeks and neurobehavior at 9 months. CONCLUSION: NIDCAP significantly improved IUGR preterm infants' neurobehavior, electrophysiology and brain structure. Longer-term outcome assessment and larger samples are recommended. PMID- 22301526 TI - Does increasing body mass index affect cerclage efficacy? AB - OBJECTIVE: To study the relationship between body mass index (BMI) and gestational age (GA) at delivery in patients with cervical insufficiency (CI) undergoing cerclage. STUDY DESIGN: We accessed a database of patients with singleton gestations undergoing cerclage (N=168) for a well-characterized history of CI, shortened cervix <2.5 cm with a history of prior preterm delivery or prolapse of membranes through the external os. Univariate and multivariate logistic regression analysis were performed to compare obstetrical outcomes between obese and normal-weight patients. RESULT: Prior preterm delivery <35 weeks in obese vs normal-weight patients was significantly higher (44% vs 9%), odds ratio=6.9 (95% CI: 2.5, 18.5), with lower mean GA at delivery (32.6+/-7.0 vs 37.2+/-3.4 weeks, P<0.001). After controlling for confounders, BMI remained significantly predictive of prematurity (coefficient: -0.12, adjusted R (2)=0.24), such that every additional 1 unit of BMI was associated with a 1-day reduction in GA at delivery (P=0.03). CONCLUSION: An inverse correlation exists between BMI and GA at delivery in patients with CI receiving cerclage. The findings are unexpected given the protective effect of obesity on spontaneous preterm delivery. PMID- 22301527 TI - History of the birth certificate: from inception to the future of electronic data. AB - Enumerations of people were carried out long before the birth of Jesus. Data related to births were recorded in church registers in England as early as the 1500s. However, not until the 1902 Act of Congress was the Bureau of Census established as a permanent agency to develop birth registration areas and a standard registration system. Although all states had birth records by 1919, the use of the standardized version was not uniformly adopted until the 1930's. In the 1989 US Standard Birth Certificate revision, the format was finally uniformly adopted to include checkboxes to improve data quality and completeness. The evolution of the 12 federal birth certificate revisions is reflected in the growth of the number of items from 33 in 1900 to more than 60 items in the 2003 birth certificate. As birth registration has moved from paper to electronic, the birth certificate's potential utility has broadened, yet issues with updating the electronic format and maintaining quality data continue to evolve. Understanding the birth certificate within its historical context allows for better insight as to how it has been and will continue to be used as an important public-health document shaping medical and public policies. PMID- 22301528 TI - Nasal intermittent positive pressure ventilation after surfactant treatment for respiratory distress syndrome in preterm infants <30 weeks' gestation: a randomized, controlled trial. AB - OBJECTIVE: To compare the effect of early extubation to nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) on the need for mechanical ventilation via endotracheal tube (MVET) at 7 days of age in preterm infants <30 weeks' gestation requiring intubation and surfactant for respiratory distress syndrome (RDS) within 60 min of delivery. STUDY DESIGN: Multicenter, randomized, controlled trial. A total of 57 infants were randomized within 120 min of birth to NCPAP (BW 1099 g and GA 27.8 weeks) and 53 infants to NIPPV (BW 1052 g, and GA 27.8 weeks). Infants were stabilized on NCPAP at birth and were given poractant alfa combined with MVET within 60 min of age. When stabilized on MVET, they were extubated within the next hours or days to NCPAP or NIPPV. RESULT: A total of 42% [corrected] of infants needed MVET at 7 days of age in the NCPAP group compared with 17% in the NIPPV group (OR: 3.6; 95% CI: 1.5, 8.7). Days on MVET were 12 +/- 11 days in NCPAP group compared with 7.5 +/- 12 days in the NIPPV group (median 1 vs 7 days; P=0.006). Clinical bronchopulmonary dysplasia (BPD) was 39% in the NCPAP group compared to 21% in the NIPPV group (OR: 2.4; 95% CI: 1.02, 5.6). Physiological BPD was 46% in the NCPAP group compared with 11% in the NIPPV group (OR: 6.6, 95% CI: 2.4, 17.8; P=0.001). There were no differences in any other outcomes between the two groups. CONCLUSION: NIPPV compared with NCPAP reduced the need for MVET in the first week, duration of MVET, and clinical as well as physiological BPD in preterm infants receiving early surfactant for RDS. PMID- 22301529 TI - Evaluation of cerebrospinal fluid parameters in preterm infants with intraventricular reservoirs. AB - OBJECTIVE: Intraventricular reservoirs (IVRs) are used to drain cerebrospinal fluid (CSF) in neonates with post-hemorrhagic ventricular dilatation (PHVD). The objectives of this case-control study were to evaluate changes in CSF parameters in serial IVR taps and to compare CSF parameters in culture-positive and negative specimens. STUDY DESIGN: Clinical and laboratory data from serial (up to 7) reservoir taps at 5- to 8-day intervals were collected on preterm neonates with PHVD and IVR insertion. RESULT: The median (range) gestational age and birth weight of our cohort (n=52) was 26 (23 to 33) weeks and 796 (450 to 1620) grams. Significant decreases in percentage of CSF neutrophils and protein were noted in later taps, compared with the first tap at insertion of IVR. Five (9.6%) infants had positive CSF cultures on 10 occasions. Compared with negative specimens (n=266), the mean (s.d.) proportion of neutrophils in CSF (55% (33) vs 26% (23)) was significantly higher and ratio of CSF to serum glucose significantly lower (0.19 (0.08) vs 0.29 (0.13)) in culture-positive specimens (n=10). The area under the curve was 0.82 (95% confidence interval (CI) 0.72 to 0.93) for CSF white blood cell (WBC) count, 0.79 (95% CI 0.68 to 0.90) for CSF protein and 0.75 (95% CI 0.56 to 0.95) for percentage of neutrophils. The sensitivities and specificities for diagnosis of infection was 90 and 63% for CSF WBC count > 42 mm(-3), 89 and 58% for CSF protein at > 250 mg dl(-1) and 80 and 67% for CSF neutrophil proportion >31.5%. CONCLUSION: CSF parameters from IVR taps, specifically proportion of neutrophils and proteins are higher at insertion and progressively normalize over time. Although they vary widely, CSF WBC, protein and neutrophil proportion using higher cut-off values have good sensitivity in the diagnosis of infection. PMID- 22301530 TI - Effect of heparin and other factors associated with complications of peripherally inserted central venous catheters in neonates. AB - OBJECTIVE: To identify factors associated with complications necessitating unplanned removal of peripherally inserted central venous catheters (PICCs) in neonates. STUDY DESIGN: A before-and-after comparison following the exclusion of heparin from continuous infusions through PICCs placed by a designated team. Duration of use was assessed during epochs immediately preceding and following the practice change. Multivariable logistic regression was performed to identify independent risk factors associated with unplanned catheter removal. RESULT: We analyzed 189 PICC placements with heparin (epoch 1) and 188 with no heparin (epoch 2) added to infusions. Rates of complication (23.7 vs 17.2 per 1000 catheter days) and median durations of use (7 vs 8 days) did not differ significantly between the epochs. Non-central position of the catheter tip, use of dual lumen catheters and placement through the cephalic vein were independently associated with complications (each P<0.05). CONCLUSION: In neonates requiring short-term intravenous access, heparin may be safely omitted from continuous infusions without compromising catheter usability. PMID- 22301531 TI - Use of smoking reduction strategies among U.S. tobacco quitlines. AB - INTRODUCTION: Tobacco quitlines (QLs) are efficacious and have assisted many smokers in achieving tobacco abstinence. However, most smokers are not able to achieve tobacco abstinence with QL services. QL counseling interventions for smokers who do not quit on their target quit date (TQD) and decline to set a new TQD after missing their TQD have not been systematically evaluated. METHODS: A telephone survey of tobacco QLs in the United States (US) was conducted to examine systematic approaches used with smokers who do not quit on their TQD and decline to set a new TQD. Tobacco QLs service providers were identified through the North American Quitline Consortium (NAQC). RESULTS: Fourteen service providers managing QLs of all 50 US states were identified and completed the voluntary survey. All providers recommended setting a new quit TQD if smokers did not achieve smoking cessation by their initial TQD. Six percent of US state QLs used brief motivational interviewing utilizing the "5R's" (relevance, risk, rewards, roadblocks, repetition). However, 90% of QLs had intervention protocols emphasizing smoking rate reduction. CONCLUSION: Although some US QLs utilized the "5Rs," the majority provided smoking reduction interventions for smokers not achieving tobacco cessation by their initial TQD and declining to set a new TQD. Research is needed to evaluate the efficacy of smoking rate reduction methods implemented through QLs for increasing smoking abstinence rates. PMID- 22301532 TI - Visible-light harvesting iridium complexes as singlet oxygen sensitizers for photooxidation of 1,5-dihydroxynaphthalene. AB - Visible-light harvesting cyclometalated Ir(III) complexes were used as (1)O(2) sensitizers for the photooxidation of 1,5-dihydroxynaphthalene (DHN) and substantially improved photooxidation capability was observed compared to the conventional Ir(III) complex sensitizers that show no visible light-harvesting capabilities. PMID- 22301533 TI - In situ electrogeneration of o-benzoquinone and high yield reaction with benzenethiols in a microflow system. AB - We have successfully demonstrated that a microflow reactor is extremely useful in controlling reactions involving an unstable o-benzoquinone. The key features of the method are an effective o-benzoquinone generation and its rapid use for the following reaction without decomposition in a microflow system. PMID- 22301534 TI - Patient advocacy and protection. PMID- 22301537 TI - Breastfeeding the premature infant and nursing implications. AB - Research indicates that feeding preterm infants at the breast is physiologically less stressful than bottle-feeding. Poor sucking reflexes make it difficult to initiate breastfeeding for these high-risk infants. Mothers need to understand the difficulties of breastfeeding, as well as the advantages for herself and her baby. It is important for nurses to be well educated on how preterm infants are breastfed and how to best support the mother through her experience. The nurse must focus on caring for the infant as well as fostering the mother-infant connection to promote breastfeeding. A mother will need continual support, encouragement, and advice from the nurse, while teaching her baby how to breastfeed. PMID- 22301538 TI - Efficacy of inhaled nitric oxide in preterm neonates. AB - Over the past 20 years, the recognition of nitric oxide (NO) as an endothelial derived vasodilator has led to remarkable advances in vascular biology awareness. The signaling molecule NO, produced by NO synthase, is a molecule that is widespread in the body and important in multiple organ systems. Soon after its discovery, investigators found NO to be a potent pulmonary vasodilator in term neonates. Nitric oxide has come to perform a key function in neonatal therapy and management since its identification, especially in those with respiratory failure. It is conventionally used in the neonatal population for the treatment of persistent pulmonary hypertension, resulting in hypoxic respiratory failure of the term or near-term newborn. Inhaled NO has been successful in acutely improving oxygenation and in reducing the need for extracorporeal membrane oxygenation treatment. In recent years, the efficacy of inhaled NO for the prevention of pulmonary disability as well as its neuroprotective capabilities in preterm infants has been explored. PMID- 22301540 TI - Carnitine palmitoyltransferase-1A deficiency: a look at classic and arctic variants. AB - Carnitine palmitoyltransferase-1A (CPT-1A) deficiency is a defect of fatty acid metabolism that presents as an autosomal recessive inheritance. Carnitine palmitoyltransferase-1A is the rate-limiting enzyme that allows the body to process fats to provide energy during times of fasting and illness. Patients usually present between birth and 18 months of age following an illness with various symptoms including hypoketotic hypoglycemia, lethargy, and seizures. Diagnosis can be achieved through newborn metabolic screening. Long-term treatment is managed through dietary management. A milder form has been found to occur at a much higher incidence in the Inuit population. Since the recent discovery of CPT-1A deficiency, much is yet to be learned. Researchers are busy identifying and studying groups of people who are presenting with CPT-1A deficiency at significantly higher rates than the general population. This research will lead to a better understanding and future care of individuals diagnosed with CPT-1A deficiency. PMID- 22301541 TI - A model program for perinatal palliative services. AB - Despite the fact that parents of infants with lethal anomalies may not want "full blown" medical care for their infants after birth, most such infants die in neonatal intensive care units. Although neonatal nurses are trained to administer life-saving treatments, they may suffer from moral distress when faced with caring for babies with incompatible-with-life conditions. This article describes a Perinatal Comfort Care program in which (a) care is provided at the time of diagnoses/antenatally and includes home visits by members of an interdisciplinary hospice team; (b) care is collaborative, community-based, and family-centered, and takes place in labor and delivery and on the mother baby unit; and (c) follow up to the family continues for 1 year after the death. Neonatal nurses can become involved either by initiating efforts to form a perinatal comfort care program or by joining an existing team. PMID- 22301542 TI - The art of effective handoffs: what is the evidence? PMID- 22301543 TI - Implementing practice guidelines and education to improve care of infants with neonatal abstinence syndrome. AB - PURPOSE: : To develop and implement a program for the management of neonatal abstinence syndrome (NAS) and the use of the Finnegan Neonatal Abstinence Scoring Tool (FNAST). We evaluated knowledge gain in nurses as a result of implementation of the practice guidelines and education. SUBJECTS: : Participants included 68 nurses employed in a neonatal intensive care unit (NICU) at a single facility. DESIGN: : A nonexperimental, pretest/posttest study evaluated change in nursing knowledge about NAS and the use of the FNAST after implementation of evidence based clinical practice guidelines and an educational project. METHODS: : Nurses were tested before and after participation in education about NAS. A subset of 10 nurses was evaluated using the FNAST with videos of infants having NAS. RESULTS: : Volunteer participation in the NAS educational project occurred in 81% of the NICU nurses. All nurses showed some improvement in scores on the posttest, with 2% to 44% improvement. All 10 nurses who participated in the interactive DVD test scored 90% or more against the FNAST criterion 1 week after participation in the educational project. CONCLUSION: : Evidence-based clinical practice guidelines and education around NAS and the FNAST equip caregivers with the necessary tools to consistently and accurately assess an infant with NAS when using the FNAST. PMID- 22301544 TI - Enteral feeding practices in the NICU: results from a 2009 Neonatal Enteral Feeding Survey. AB - PURPOSE: : The purpose of this study was to examine the current management of the enteral feeding regimens of premature infants cared for in the neonatal intensive care unit (NICU). SUBJECTS: : The study included responses from 70 neonatal nurses who participated in a 2009 Neonatal Enteral Feeding Survey distributed electronically to the National Association of Neonatal Nurses membership. These respondents were representative of both the United States and Canada, with 29 US states represented. The majority of respondents (95.7%) reported current nursing employment in a level III NICU. DESIGN: : Survey research was used in this exploratory study. The survey, Enteral Tube Feeding Practices in the Neonatal Intensive Care Unit, was developed in collaboration with expert neonatal nurses and nutritionists, pilot tested, and distributed via electronic means. METHODS: : Survey research was conducted according to the Dillman methodology. Data analysis included descriptive statistics and univariate analysis of variance assessing for significant differences in specific neonatal feeding practices reported. Thematic analysis was used to analyze the qualitative data reported. OUTCOME MEASURES: : The outcome measures included the survey responses to the questions asked about the implementation of an enteral feeding protocol and various aspects of enteral feeding practices in the NICU. RESULTS: : The majority of participants (60.9%) reported that an enteral feeding protocol was implemented in practice, but that it was inconsistently followed because of individual physician or nurse practice patterns, or highly individualized feeding plans required of specific clinical care needs of the patient. Respondents indicated that gestational age was the leading criteria used to initiate feedings, and patent ductus arteriosis treatment was the primary contraindication to enteral feedings. The leading factor reported to delay or alter enteral feedings was the presence of gastric residuals. Survey data indicated that other contraindicating factors to enteral feeding are variable across NICUs and, as reported, are often inconsistent with the current research published to date. CONCLUSIONS: : Research is needed to provide a foundation on which to develop effective enteral feeding protocols that are appropriate for the diversity of infants cared for in the NICU. Such research findings will culminate in the development and implementation of enteral feeding protocols in the NICU, which will result in improved nutrition, growth, and development outcomes for premature infants. PMID- 22301545 TI - Structural and functional characterization of a novel nonglycosidic type I NKT agonist with immunomodulatory properties. AB - Activation of type I NKT (iNKT) cells by CD1d-presented agonists is a potent immunotherapeutic tool. alpha-Galactosylceramide (alpha-GalCer) is the prototypic agonist, but its excessive potency with simultaneous production of both pro- and anti-inflammatory cytokines hampers its potential therapeutic use. In search for novel agonists, we have analyzed the structure and function of HS44, a synthetic aminocyclitolic ceramide analog designed to avoid unrestrained iNKT cell activation. HS44 is a weaker agonist compared with alpha-GalCer in vitro, although in vivo it induces robust IFN-gamma production, and highly reduced but still functional Th2 response. The characteristic cytokine storm produced upon alpha-GalCer activation was not induced. Consequently, HS44 induced a very efficient iNKT cell-dependent antitumoral response in B16 animal model. In addition, intranasal administration showed the capacity to induce lung inflammation and airway hyperreactivity, a cardinal asthma feature. Thus, HS44 is able to elicit functional Th1 or Th2 responses. Structural studies show that HS44 binds to CD1d with the same conformation as alpha-GalCer. The TCR binds to HS44 similarly as alpha-GalCer, but forms less contacts, thus explaining its weaker TCR affinity and, consequently, its weaker recognition by iNKT cells. The ability of this compound to activate an efficient, but not massive, tailored functional immune response makes it an attractive reagent for immune manipulation. PMID- 22301546 TI - The MC159 protein from the molluscum contagiosum poxvirus inhibits NF-kappaB activation by interacting with the IkappaB kinase complex. AB - Molluscum contagiosum virus (MCV) causes persistent neoplasms in healthy and immunocompromised people. Its ability to persist likely is due to its arsenal of viral immunoevasion proteins. For example, the MCV MC159 protein inhibits TNF-R1 induced NF-kappaB activation and apoptosis. The MC159 protein is a viral FLIP and, as such, possesses two tandem death effector domains (DEDs). We show in this article that, in human embryonic kidney 293 T cells, the expression of wild-type MC159 or a mutant MC159 protein containing the first DED (MC159 A) inhibited TNF induced NF-kappaB, or NF-kappaB activated by PMA or MyD88 overexpression, whereas a mutant protein lacking the first DED (MC159 B) did not. We hypothesized that the MC159 protein targeted the IkappaB kinase (IKK) complex to inhibit these diverse signaling events. Indeed, the MC159 protein, but not MC159 B, coimmunoprecipitated with IKKgamma. MC159 coimmunoprecipitated with IKKgamma when using mouse embryonic fibroblasts that lack either IKKalpha or IKKbeta, suggesting that the MC159 protein interacted directly with IKKgamma. MC159 IKKgamma coimmunoprecipitations were detected during infection of cells with either MCV isolated from human lesions or with a recombinant MC159-expressing vaccinia virus. MC159 also interacts with TRAF2, a signaling molecule involved in NF-kappaB activation. However, mutational analysis of MC159 failed to reveal a correlation between MC159-TRAF2 interactions and MC159's inhibitory function. We propose that MC159-IKK interactions, but not MC159-TRAF2 interactions, are responsible for inhibiting NF-kappaB activation. PMID- 22301547 TI - HER2/HER3 signaling regulates NK cell-mediated cytotoxicity via MHC class I chain related molecule A and B expression in human breast cancer cell lines. AB - Overexpression of the receptor tyrosine kinases HER2 and HER3 is associated with a poor prognosis in several types of cancer. Presently, HER2- as well as HER3 targeted therapies are in clinical practice or evaluated within clinical trials, including treatment with mAbs mediating growth inhibition and/or activation of Ab induced innate or adaptive cellular immunity. A better understanding of how HER2/HER3 signaling in tumors influences cellular immune mechanisms is therefore warranted. In this study, we demonstrate that HER2/HER3 signaling regulates the expression of MHC class I-related chain A and B (MICA and MICB) in breast cancer cell lines. The MICA and MICB (MICA/B) molecules act as key ligands for the activating receptor NK group 2, member D (NKG2D) and promote NK cell-mediated recognition and cytolysis. Genetic silencing of HER3 but not HER2 downregulated the expression of MICA/B, and HER3 overexpression significantly enhanced MICA expression. Among the major pathways activated by HER2/HER3 signaling, the PI3K/AKT pathway was shown to predominantly regulate MICA/B expression. Treatment with the HER3-specific ligand neuregulin 1beta promoted the expression in a process that was antagonized by pharmacological and genetic interference with HER3 but not by the ataxia-telangiectasia-mutated (ATM) and ATM and Rad3-related protein kinases inhibitor caffeine. These observations further emphasize that HER2/HER3 signaling directly, and not via genotoxic stress, regulates MICA/B expression. As anticipated, stimulating HER2/HER3 enhanced the NKG2D-MICA/B dependent NK cell-mediated cytotoxicity. Taken together, we conclude that signaling via the HER2/HER3 pathway in breast carcinoma cell lines may lead to enhanced NKG2D-MICA/B recognition by NK cells and T cells. PMID- 22301548 TI - Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. AB - It is estimated that 1 billion people around the world are vitamin D deficient. Vitamin D deficiency has been linked to various inflammatory diseases. However, the mechanism by which vitamin D reduces inflammation remains poorly understood. In this study, we investigated the inhibitory effects of physiologic levels of vitamin D on LPS-stimulated inflammatory response in human blood monocytes and explored potential mechanisms of vitamin D action. We observed that two forms of the vitamin D, 1,25(OH)(2)D(3), and 25(OH)D(3), dose dependently inhibited LPS induced p38 phosphorylation at physiologic concentrations, IL-6 and TNF-alpha production by human monocytes. Upon vitamin D treatment, the expression of MAPK phosphatase-1 (MKP-1) was significantly upregulated in human monocytes and murine bone marrow-derived macrophages (BMM). Increased binding of the vitamin D receptor and increased histone H4 acetylation at the identified vitamin D response element of the murine and human MKP-1 promoters were demonstrated. Moreover, in BMM from MKP1(-/-) mice, the inhibition of LPS-induced p38 phosphorylation by vitamin D was completely abolished. Vitamin D inhibition of LPS-induced IL-6 and TNF-alpha production by BMM from MKP-1(-/-) mice was significantly reduced as compared with wild-type mice. In conclusion, this study identified the upregulation of MKP-1 by vitamin D as a novel pathway by which vitamin D inhibits LPS-induced p38 activation and cytokine production in monocytes/macrophages. PMID- 22301551 TI - Real-time assessment of community health needs and concerns. AB - The August 2011 Clinical and Translational Science Awards conference "Using IT to Improve Community Health: How Health Care Reform Supports Innovation" convened four "Think Tank" sessions. This report summarizes the content of one session centered on "Social Networking: Community Connections and Health Outcomes." We discuss the efforts of HealthStreet to facilitate ongoing, real-time assessment of community health needs, concerns, and opportunities to participate in research. PMID- 22301550 TI - Using health information technology to engage communities in health, education, and research. AB - The August 2011 Clinical and Translational Science Awards conference "Using IT to Improve Community Health: How Health Care Reform Supports Innovation" convened four "Think Tank" sessions. Thirty individuals, representing various perspectives on community engagement, attended the "Health information technology (HIT) as a resource to improve community health and education" session, which focused on using HIT to improve patient health, education, and research involvement. Participants discussed a range of topics using a semistructured format. This article describes themes and lessons that emerged from that session, with a particular focus on using HIT to engage communities to improve health and reduce health disparities in populations. PMID- 22301552 TI - Meaningful use of electronic behavioral health data in primary health care. AB - In August 2011, scientists and policy-makers held a conference entitled "Using IT to Improve Community Health: How Health Care Reform Supports Innovation." One of the conference sessions was entitled "Electronic health records: Meaningful use implementation challenges, innovation, and regulations." This Meeting Report discusses the meaningful use of behavioral health data for the treatment of mental health and substance abuse conditions and optimization of behavioral wellness by primary care physicians. PMID- 22301553 TI - Geomapping health-related data. AB - In August 2011, scientists and policy-makers held a conference entitled "Using IT to Improve Community Health: How Health Care Reform Supports Innovation." One of the conference sessions was entitled "Geo-mapping: Framing health needs and issues as an individual and community concern." This Meeting Report describes how geographical information systems can be used to analyze health-related data for medical care and policy making. PMID- 22301554 TI - Massage therapy attenuates inflammatory signaling after exercise-induced muscle damage. AB - Massage therapy is commonly used during physical rehabilitation of skeletal muscle to ameliorate pain and promote recovery from injury. Although there is evidence that massage may relieve pain in injured muscle, how massage affects cellular function remains unknown. To assess the effects of massage, we administered either massage therapy or no treatment to separate quadriceps of 11 young male participants after exercise-induced muscle damage. Muscle biopsies were acquired from the quadriceps (vastus lateralis) at baseline, immediately after 10 min of massage treatment, and after a 2.5-hour period of recovery. We found that massage activated the mechanotransduction signaling pathways focal adhesion kinase (FAK) and extracellular signal-regulated kinase 1/2 (ERK1/2), potentiated mitochondrial biogenesis signaling [nuclear peroxisome proliferator activated receptor gamma coactivator 1alpha (PGC-1alpha)], and mitigated the rise in nuclear factor kappaB (NFkappaB) (p65) nuclear accumulation caused by exercise induced muscle trauma. Moreover, despite having no effect on muscle metabolites (glycogen, lactate), massage attenuated the production of the inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and reduced heat shock protein 27 (HSP27) phosphorylation, thereby mitigating cellular stress resulting from myofiber injury. In summary, when administered to skeletal muscle that has been acutely damaged through exercise, massage therapy appears to be clinically beneficial by reducing inflammation and promoting mitochondrial biogenesis. PMID- 22301555 TI - CXCL12-induced monocyte-endothelial interactions promote lymphocyte transmigration across an in vitro blood-brain barrier. AB - The accumulation of inflammatory cells in the brain parenchyma is a critical step in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). Chemokines and adhesion molecules orchestrate leukocyte transmigration across the blood-brain barrier (BBB), but the dynamics of chemokine receptor expression during leukocyte transmigration are unclear. We describe an in vitro BBB model system using human brain microvascular endothelial cells that incorporates shear forces mimicking blood flow to elucidate how chemokine receptor expression is modulated during leukocyte transmigration. In the presence of the chemokine CXCL12, we examined modulation of its receptor CXCR4 on human T cells, B cells, and monocytes transmigrating across the BBB under flow conditions. CXCL12 stimulated transmigration of CD4(+) and CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes. Transmigration was blocked by CXCR4 neutralizing antibodies. Unexpectedly, CXCL12 selectively down-regulated CXCR4 on transmigrating monocytes, but not T cells. Monocytes underwent preferential CXCL12-mediated adhesion to the BBB in vitro compared with lymphocytes. These findings provide new insights into leukocyte-endothelial interactions at the BBB under conditions mimicking blood flow and suggest that in vitro BBB models may be useful for identifying chemokine receptors that could be modulated therapeutically to reduce neuroinflammation in diseases such as MS. PMID- 22301556 TI - The anti-trypanosome drug fexinidazole shows potential for treating visceral leishmaniasis. AB - Safer and more effective oral drugs are required to treat visceral leishmaniasis, a parasitic disease that kills 50,000 to 60,000 people each year in parts of Asia, Africa, and Latin America. Here, we report that fexinidazole, a drug currently in phase 1 clinical trials for treating African trypanosomiasis, shows promise for treating visceral leishmaniasis. This 2-substituted 5-nitroimidazole drug is rapidly oxidized in vivo in mice, dogs, and humans to sulfoxide and sulfone metabolites. Both metabolites of fexinidazole were active against Leishmania donovani amastigotes grown in macrophages, whereas the parent compound was inactive. Pharmacokinetic studies with fexinidazole (200 mg/kg) showed that fexinidazole sulfone achieves blood concentrations in mice above the EC(99) (effective concentration inhibiting growth by 99%) value for at least 24 hours after a single oral dose. A once-daily regimen for 5 days at this dose resulted in a 98.4% suppression of infection in a mouse model of visceral leishmaniasis, equivalent to that seen with the drugs miltefosine and Pentostam, which are currently used clinically to treat this tropical disease. In African trypanosomes, the mode of action of nitro drugs involves reductive activation via a NADH (reduced form of nicotinamide adenine dinucleotide)-dependent bacterial like nitroreductase. Overexpression of the leishmanial homolog of this nitroreductase in L. donovani increased sensitivity to fexinidazole by 19-fold, indicating that a similar mechanism is involved in both parasites. These findings illustrate the potential of fexinidazole as an oral drug therapy for treating visceral leishmaniasis. PMID- 22301557 TI - Talking to patients: barriers to overcome. PMID- 22301558 TI - Posttraumatic stress disorder, depression, and suicide in veterans. AB - Suicidal behavior is a critical problem in war veterans. Combat veterans are not only more likely to have suicidal ideation, often associated with posttraumatic stress disorder (PTSD) and depression, but they are more likely to act on a suicidal plan. Especially since veterans may be less likely to seek help from a mental health professional, non-mental-health physicians are in a key position to screen for PTSD, depression, and suicidal ideation in these patients. The authors discuss the association of PTSD, depression, and suicide in veterans, keys to assessment of suicide risk, and interventions. PMID- 22301559 TI - A 48-year-old woman with an ecchymotic rash. PMID- 22301560 TI - Chest pain followed by sudden collapse. PMID- 22301561 TI - Deep brain stimulation: what can patients expect from it? AB - Deep brain stimulation has largely replaced ablative procedures for the treatment of advanced Parkinson disease, essential tremor, and dystonia. It is also approved for obsessive-compulsive disorder. Although not curative, it improves symptoms and quality of life. PMID- 22301562 TI - Finding the cause of acute kidney injury: which index of fractional excretion is better? AB - The fractional excretion of urea (FEU) is a useful index for differentiating the main categories of causes of acute kidney injury, ie, prerenal causes and intrinsic causes. It may be used in preference to the more widely used fractional excretion of sodium (FENa) in situations in which the validity of the latter is limited, such as in patients taking a diuretic. PMID- 22301563 TI - Overcoming health care disparities via better cross-cultural communication and health literacy. AB - Health care disparities have multiple causes; the dynamics of the physician patient encounter is one of the causes that can be modified. Here, we discuss specific recommendations related to cross-cultural communication and health literacy as practical steps to providing more equitable health care to all patients. PMID- 22301564 TI - New and future therapies for lupus nephritis. AB - Based on data from randomized controlled trials over the past decade, oral mycophenolate (CellCept) now rivals intravenous cyclophosphamide (Cytoxan) as a first-line therapy for lupus nephritis, offering similar efficacy but less toxicity. The roles of rituximab (Rituxan) and new immunomodulatory agents are being explored. Creativity in treating lupus nephritis is needed; one regimen does not fit all. PMID- 22301565 TI - A 37-year-old man with a chronic cough. PMID- 22301566 TI - A study of M-X-BR3 (M = Pt, Pd or Rh; X = Cl or I) interactions in square planar ambiphilic ligand complexes: structural, spectroscopic, electrochemical and computational comparisons with borane-free analogues. AB - Reaction of [PtCl(2)(COD)] and [PtI(2)(COD)] with 2,7-di-tert-butyl-5 diphenylboryl-4-diphenylphosphino-9,9-dimethylthioxanthene (TXPB) afforded square planar [PtCl(2)(TXPB)] (1B) and [PtI(2)(TXPB)] (4B), both of which were crystallographically characterized. Single-crystal X-ray quality crystals were also obtained for [PdCl(2)(TXPB)] (2B; Emslie et al., Organometallics, 2008, 27, 5317) as 2B.2CH(2)Cl(2) and solvent-free 2B. Both the chloro and iodo TXPB complexes exhibit metal-halide-borane bridging interactions similar to those in previously reported [RhCl(CO)(TXPB)] (3B) and [RhI(CO)(TXPB)] (5B) (Emslie et al., Organometallics, 2006, 25, 583 and Inorg. Chem., 2010, 49, 4060). To facilitate a more detailed analysis of M-X-BR(3) (X = Cl and I) interactions, a borane-free analogue of the TXPB ligand, 2,7-di-tert-butyl-4-diphenylphosphino 9,9-dimethylthioxanthene (TXPH), was prepared. Reaction with [PtX(2)(COD)] (X = Cl or I), [PdCl(2)(COD)] and 0.5 [{RhCl(CO)(2)}(2)] provided square planar [PtCl(2)(TXPH)] (1H), [PdCl(2)(TXPH)] (2H), [RhCl(CO)(TXPH)] (3H) and [PtI(2)(TXPH)] (4H). M-Cl-BR(3) and M-I-BR(3) bonding in 1B-5B was then probed through the use of structural comparisons, IR and NMR spectroscopy, cyclic voltammetry, and DFT calculations (Slater-type orbitals, Mayer bond orders, Hirshfeld charges, fragment analysis, SCF deformation density isosurfaces, and energy decomposition analysis). PMID- 22301567 TI - Type D personality and Alexithymia among psychiatric outpatients. PMID- 22301568 TI - Fetoscopy and risk of iatrogenic preterm premature rupture of membranes: not as high as it may seem (in experienced hands). PMID- 22301569 TI - Does vaginal irrigation with saline solution in women with infectious vaginitis contribute to the clinical and microbiological results of antibiotic therapy? AB - AIM: To compare the clinical and microbiological results between patients with infectious vaginitis receiving vaginal irrigation with saline or no irrigation before standard antibiotic therapy. METHODS: Women with vaginitis (n = 109) were randomized to receive vaginal irrigation with saline or no irrigation before standard antibiotic therapy. The vaginal symptoms perceived by subjects and clinical findings were assessed with a standardized scale during four follow-up visits, and Gram stain Nugent scores and vaginal fluid cultures were analyzed at each visit. RESULTS: Vaginal discharge (z = 7.159; p < 0.001), pruritus (z = 5.169; p < 0.001), itching (z = 2.969; p < 0.003) and odor scores (z = 2.303; p < 0.021) were significantly reduced in the study group compared to the control group between the first visit and 3-5 days after irrigation, before the start of antibiotic therapy. The second and third visits (15 and 30-45 days after antibiotic therapy) showed that the patients' symptoms and amounts of visible vaginal discharge did not differ between the two groups. Moreover, the microbiological cures of patients in each group did not differ at these visits (z = 0.447; p = 0.655). CONCLUSION: Vaginal irrigation with saline significantly reduces self-reported symptoms in the short term but has no effect on long-term clinical and laboratory results in women with infectious vaginitis. PMID- 22301570 TI - Intrauterine exposure to mild analgesics during pregnancy and the occurrence of cryptorchidism and hypospadia in the offspring: the Generation R Study. AB - BACKGROUND: Recently, over-the-counter mild analgesic use during pregnancy has been suggested to influence the risk of reproductive disorders in the offspring. We examined the influence of maternal exposure to mild analgesics during pregnancy on the occurrence of cryptorchidism and hypospadia in their offspring. METHODS: Associations between maternal exposure to mild analgesics during pregnancy and cryptorchidism or hypospadia in the offspring were studied in 3184 women participating in a large population-based prospective birth cohort study from early pregnancy onwards in the Netherlands (2002-2006), the Generation R Study. Cryptorchidism and hypospadia were identified during routine screening assessments performed in child health care centres by trained physicians. The use of mild analgesics was assessed in three prenatal questionnaires in pregnancy, resulting in four periods of use, namely, periconception period, first 14 weeks of gestation, 14-22 weeks of gestation and 20-32 weeks of gestation. Logistic regression analyses were used to study the associations between maternal exposure to mild analgesics and cryptorchidism and hypospadia. RESULTS: The cumulative prevalence over 30 months of follow up was 2.1% for cryptorchidism and 0.7% for hypospadia. Use of mild analgesics in the second period of pregnancy (14-22 weeks) increased the risk of congenital cryptorchidism [adjusted odds ratio (OR) 2.12; 95% confidence interval (CI) 1.17-3.83], primarily due to the use of acetaminophen (paracetamol) (adjusted OR 1.89; 95% CI 1.01-3.51). Among mothers of cryptorchid sons, 33.8% reported (23 of 68) the use of mild analgesics during pregnancy, compared with 31.8% (7 of 22) of mothers with a boy with hypospadia and 29.9% (926 of 3094) of mothers with healthy boys. CONCLUSIONS: Our results suggest that intrauterine exposure to mild analgesics, primarily paracetamol, during the period in pregnancy when male sexual differentiation takes place, increases the risk of cryptorchidism. PMID- 22301571 TI - Predictors of adverse outcomes on an acute geriatric rehabilitation ward. AB - BACKGROUND: multidisciplinary rehabilitation is of proven benefit in the management of older inpatients. However, the identification of patients who will do well with rehabilitation currently lacks a strong evidence base. OBJECTIVES: the aims of this study were to compare the importance of chronological age, gender, co-morbidities and frailty in the prediction of adverse outcomes for patients admitted to an acute geriatric rehabilitation ward. DESIGN: prospective observational cohort study. SUBJECTS AND SETTING: two hundred and sixty-five patients admitted consecutively to an acute geriatric rehabilitation ward at a tertiary care teaching hospital. METHODS: frailty status was measured by an index of accumulated deficits, giving a potential score from 0 (no deficits) to 1.0 (all 40 deficits present). Patients were stratified into three outcomes: good (discharged to original residence within 28 days), intermediate (discharged to original residence but longer hospital stay) and poor (newly institutionalised or died). RESULTS: patients were old (82.6 +/- 8.6 years) and frail (mean frailty index (FI) 0.34 +/- 0.09). Frailty status correlated significantly with length of stay and was a predictor of poor functional gain. The odds ratio of intermediate and poor outcome relative to a good outcome was 4.95 (95% CI = 3.21, 7.59; P < 0.001) per unit increase in FI. Chronological age, gender and co-morbidity showed no significant association with outcomes. CONCLUSION: frailty is associated with adverse rehabilitation outcomes. The FI may have clinical utility, augmenting clinical judgement in the management of older inpatients. PMID- 22301572 TI - The arcuate nucleus of the C57BL/6J mouse hindbrain is a displaced part of the inferior olive. AB - The arcuate nucleus is a prominent cell group in the human hindbrain, characterized by its position on the pial surface of the pyramid. It is considered to be a precerebellar nucleus and has been implicated in the pathology of several disorders of respiration. An arcuate nucleus has not been convincingly demonstrated in other mammals, but we have found a similarly positioned nucleus in the C57BL/6J mouse. The mouse arcuate nucleus consists of a variable group of neurons lying on the pial surface of the pyramid. The nucleus is continuous with the ventrolateral part of the principal nucleus of the inferior olive and both groups are calbindin positive. At first we thought that this mouse nucleus was homologous with the human arcuate nucleus, but we have discovered that the neurons of the human nucleus are calbindin negative, and are therefore not olivary in nature. We have compared the mouse arcuate neurons with those of the inferior olive in terms of molecular markers and cerebellar projection. The neurons of the arcuate nucleus and of the inferior olive share three major characteristics: they both contain neurons utilizing glutamate, serotonin or acetylcholine as neurotransmitters; they both project to the contralateral cerebellum, and they both express a number of genes not present in the major mossy fiber issuing precerebellar nuclei. Most importantly, both cell groups express calbindin in an area of the ventral hindbrain almost completely devoid of calbindin-positive cells. We conclude that the neurons of the hindbrain mouse arcuate nucleus are a displaced part of the inferior olive, possibly separated by the caudal growth of the pyramidal tract during development. The arcuate nucleus reported in the C57BL/6J mouse can therefore be regarded as a subgroup of the rostral inferior olive, closely allied with the ventral tier of the principal nucleus. PMID- 22301574 TI - A versatile platform for highly sensitive detection of protein: DNA enriching magnetic nanoparticles based rolling circle amplification immunoassay. AB - A novel rolling circle amplification (RCA) immunoassay based on DNA enriching magnetic nanoparticles and assembled fluorescent DNA nanotags, magnetic nanoparticles-RCA immunoassay, is developed as a versatile fluorescence assay platform for highly sensitive proteins detection. PMID- 22301575 TI - Iodine-stabilized Cu nanoparticle chitosan composite for antibacterial applications. AB - We report herein the synthesis of a new composite consisting of Cu nanoparticles (NPs) and chitosan (CS), which has been found to be stable in the presence of molecular iodine and has also high antimicrobial activities. The composite could be obtained when aqueous CuSO(4) was treated with hydrazine in the presence of CS. The spherical Cu NPs present in the composite were of average diameters 8+/-4 nm. The NPs were unstable in atmospheric conditions leading to the formation of oxides of Cu. On the other hand, when molecular iodine was added to the medium following synthesis the NPs were rather stable. Studies of antibacterial property were carried out on Gram-negative green fluorescent expressing Escherichia coli bacteria & Gram-positive Bacillus cereus bacteria. The minimum inhibitory concentration (MIC) of the iodinated composite on Escherichia coli was found to be 130.8 MUg/mL, which contained 21.5 MUg/mL Cu NPs. This determined value of MIC for Cu NPs was much lower than those reported in the literature. Zeta potential (zeta) measurements supported an attractive interaction between iodinated CS-Cu NP composite and bacteria which was further supported by electron microscopic images. Electron microscopic and flow cytometric studies revealed that the iodinated CS-Cu NP composite was attached to the bacterial cell wall, which caused irreversible damage to the membrane, eventually leading to cell death. Mechanism of bactericidal action of the iodinated composite is discussed in light of our findings. PMID- 22301576 TI - A self-consistent DFT + DMFT scheme in the projector augmented wave method: applications to cerium, Ce2O3 and Pu2O3 with the Hubbard I solver and comparison to DFT + U. AB - An implementation of full self-consistency over the electronic density in the DFT + DMFT framework on the basis of a plane wave-projector augmented wave (PAW) DFT code is presented. It allows for an accurate calculation of the total energy in DFT + DMFT within a plane wave approach. In contrast to frameworks based on the maximally localized Wannier function, the method is easily applied to f electron systems, such as cerium, cerium oxide (Ce2O3) and plutonium oxide (Pu2O3). In order to have a correct and physical calculation of the energy terms, we find that the calculation of the self-consistent density is mandatory. The formalism is general and does not depend on the method used to solve the impurity model. Calculations are carried out within the Hubbard I approximation, which is fast to solve, and gives a good description of strongly correlated insulators. We compare the DFT + DMFT and DFT + U solutions, and underline the qualitative differences of their converged densities. We emphasize that in contrast to DFT + U, DFT + DMFT does not break the spin and orbital symmetry. As a consequence, DFT + DMFT implies, on top of a better physical description of correlated metals and insulators, a reduced occurrence of unphysical metastable solutions in correlated insulators in comparison to DFT + U. PMID- 22301605 TI - Improvements in compliance with resuscitation bundles and achievement of end points after an educational program on the management of severe sepsis and septic shock. AB - The objectives of this study were to determine whether an educational program could improve compliance with resuscitation bundles and the outcomes of patients with severe sepsis or septic shock and to evaluate which resuscitation bundle end points were associated with in-hospital mortality. This was a retrospective observational study of 366 patients (163 of historical controls and 203 of treatment patients) with severe sepsis or septic shock who presented to the emergency department between May 2007 and July 2009. Compliance with resuscitation bundles and achievement of the corresponding end points were compared before and after the 3-month educational program. Compliance with central line insertion and monitoring of central venous pressure (29% vs. 67%, P < 0.001) and central venous oxygen saturation (ScvO2) (25% vs. 68%, P < 0.001) was significantly improved after the educational program. The achievement of target ScvO2 within the first 6 h was significantly improved (62% vs. 88%, P < 0.001). In-hospital mortality was independently associated with adequate fluid challenge (odds ratio [OR], 0.161; 95% confidence interval [CI], 0.046-0.559) and the achievement of target mean arterial pressure (OR, 0.056; 95% CI, 0.008-0.384) and ScvO2 (OR, 0.251; 95% CI, 0.072-0.875) among the five sepsis resuscitation bundles. In conclusion, an educational program can improve compliance with resuscitation bundles and achievement of their corresponding end points. PMID- 22301606 TI - Structural changes of the heart during severe sepsis or septic shock. AB - Cardiovascular dysfunction is common in severe sepsis or septic shock. Although functional alterations are often described, the elevated serum levels of cardiac proteins and autopsy findings of myocardial immune cell infiltration, edema, and damaged mitochondria suggest that structural changes to the heart during severe sepsis and septic shock may occur and may contribute to cardiac dysfunction. We explored the available literature on structural (versus functional) cardiac alterations during experimental and human endotoxemia and/or sepsis. Limited data suggest that the structural changes could be prevented, and myocardial function improved by (pre-)treatment with platelet-activating factor, cyclosporin A, glutamine, caffeine, simvastatin, or caspase inhibitors. PMID- 22301607 TI - Guanine-nucleotide exchange factor H1 mediates lipopolysaccharide-induced interleukin 6 and tumor necrosis factor alpha expression in endothelial cells via activation of nuclear factor kappaB. AB - The development of sepsis is multifactorial. Tissue damage and organ dysfunction may be caused not only by the microorganisms but also by the inflammatory mediators released in response to the infection. Interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) levels in serum are well known to be upregulated in humans with sepsis and can be used to predict outcome. Using human umbilical vein endothelial cells, we analyzed the role of guanine-nucleotide exchange factor H1 (GEF-H1) on lipopolysaccharide (LPS)-dependent IL-6/TNF-alpha expression in endothelial cells. Lipopolysaccharide upregulated IL-6 secretion in a dose- and time-dependent manner. Specific inactivation of RhoA/Cdc42/Rac1 by Clostridium difficile toxin B-10463 (TcdB-10463) reduced LPS-induced nuclear factor kappaB (NF-kappaB) p65 phosphorylation, IL-6/TNF-alpha messenger RNA (mRNA), and IL-6/TNF-alpha protein productions. Guanine-nucleotide exchange factor H1 protein expression remained on a high level among 1 to 9 h in response to LPS challenge of endothelial cells. Inhibition of GEF-H1 by specific small interfering RNA or inactivation of Rho-associated kinase with Y-27632 not only significantly reduced LPS-induced p38 and extracellular signal-regulated kinase 1/2 (ERK1/2) activities but also blocked LPS-induced NF-kappaB translocation and activation, thereby inhibiting IL-6/TNF-alpha mRNA and protein productions. Furthermore, SB203580 (p38 inhibitor) but not PD98059 (ERK1/2 inhibitor) blocked LPS-induced NF-kappaB activation; however, both inhibitors significantly suppressed IL-6/TNF-alpha mRNA and protein expression. In summary, our data suggest that LPS rapidly upregulates GEF-H1 expression. Activated Rho-associated kinase by GEF-H1 subsequently activates p38 and ERK1/2, thereby increasing IL 6/TNF-alpha expression in endothelial cells. P38 and ERK1/2 regulate LPS-induced IL-6/TNF-alpha expression through an NF-kappaB-dependent manner and an NF-kappaB independent manner, respectively. PMID- 22301608 TI - The carcinoembryonic antigen level in pancreatic juice and mural nodule size are predictors of malignancy for branch duct type intraductal papillary mucinous neoplasms of the pancreas. AB - OBJECTIVE: Identification of predictors of malignancy for branch duct type intraductal papillary mucinous neoplasms (IPMN). BACKGROUND: Main duct type IPMN has been recommended for resection. However, the indications for resection of the branch duct type IPMN have been controversial. METHODS: We retrospectively analyzed the clinicopathological factors of 134 patients undergoing resection for branch duct type IPMN, excluding main duct type IPMN, to identify predictors of the malignant behavior of this neoplasm. The cutoff values of tumor size, main pancreatic duct (MPD) size, mural nodule size, and carcinoembryonic antigen (CEA) level in the pancreatic juice obtained during preoperative endoscopic retrograde pancreatography (ERP) were analyzed using receiver-operator characteristic curves. RESULTS: We found 7 significant predictors for malignancy in the branch duct type IPMN in a univariate analysis; jaundice, tumor occupying the pancreatic head, MPD size >5 mm, mural nodule size >5 mm, serum carbohydrate antigen (CA)19 9 level, positive cytology in the pancreatic juice, and CEA level in the pancreatic juice >30 ng/mL. In a multivariate analysis, a mural nodule size >5 mm and a CEA level in the pancreatic juice >30 ng/mL were independent factors associated with malignancy. The positive predictive value of a mural nodule size >5 mm and a CEA level in the pancreatic juice >30 ng/mL was 100%, and the negative predictive value was 96.3%. CONCLUSIONS: We identified 2 useful predictive factors for malignancy in branch duct type IPMN; a mural nodule size >5 mm and a CEA level in the pancreatic juice obtained by preoperative ERP >30 ng/mL. PMID- 22301609 TI - Meta-analysis of clinical efficacy of pulsed radio frequency energy treatment. AB - OBJECTIVE: To statistically evaluate published clinical efficacy data related to the use of pulsed radio frequency energy (PRFE) therapy in 3 clinical applications. BACKGROUND: Numerous clinical studies have reported efficacy outcomes for PRFE therapy use in the palliative treatment of both postoperative and nonpostoperative pain and edema, and for its use as an adjunctive wound healing (WH) therapeutic. Although diverse in design and endpoint, these studies are amenable to systematic review using both a vote-counting and P-value combination meta-analytic technique. METHODS: A meta-analysis of efficacy outcomes reported in clinical trials was performed using a vote-counting procedure. In addition, when possible, the sum of logs method of P-value combination was used to determine a significance level for the combined evidence within each endpoint and clinical area. RESULTS: Of the 186 clinical articles identified after application of selection criteria, there were 25 controlled trials that met criteria for inclusion in vote-counting and P-value combination methods and were used for formal statistical analysis. In total, 1332 patients receiving PRFE treatment were studied. Vote-counting procedure applied to clinical outcomes from controlled studies resulted in a greater number of positive outcomes than neutral outcomes, and zero negative outcomes, for each of the clinical application groups evaluated. The sum of logs P-value method found statistically significant improvement in pain, reduction in edema, and improvement in WH outcomes. CONCLUSIONS: On the basis of statistical evaluation of published clinical efficacy data, there is strong statistical evidence that PRFE therapy is effective in the treatment of postoperative and nonpostoperative pain and edema and in WH applications. PMID- 22301611 TI - Gastroenteritis caused by Campylobacter concisus. AB - We describe a case of gastroenteritis caused by Campylobacter concisus. The pathogenic potential of C. concisus has yet to be elucidated. Recent studies indicate an association with enteric disease in immunocompromised patients and inflammatory bowel disease in children. Molecular identification methods may be necessary for identifying certain Campylobacter species because of phenotypic similarity. PMID- 22301612 TI - Kytococcus schroeteri endocarditis successfully managed with daptomycin: a case report and review of the literature. AB - Kytococcus shroeteri is a rare cause of prosthetic valve endocarditis. Here, we report what is believed to be the first case of K. schroeteri endocarditis to be treated successfully by daptomycin and review the published literature of K. schroeteri endocarditis. There are no published daptomycin susceptibility data for Kytococcus and additional work was carried out on six other isolates stored at the Laboratory of HealthCare Associated Infections (LHCAI), Health Protection Agency (HPA) Centre for Infections, Colindale, London. PMID- 22301613 TI - Interaction of Burkholderia pseudomallei and Burkholderia thailandensis with human monocyte-derived dendritic cells. AB - Burkholderia pseudomallei is the causative agent of melioidosis, a disease endemic in areas of South-East Asia and northern Australia, and is classed as a category B select agent by the Centers for Disease Control and Prevention (CDC). Factors that determine whether host infection is achieved or if disease is chronic or acute are unknown but the type of host immune response that is mounted is important. B. pseudomallei can replicate within macrophages, causing them to multinucleate. In light of the common lineage of macrophages with dendritic cells (DCs), and the role played by DCs in orchestration of the immune response, we investigated the interactions of a variety of B. pseudomallei and B. thailandensis strains with DCs. This study demonstrates that, in the majority of cases, infection of human monocyte-derived dendritic cells is dramatically decreased or cleared by 12 h post-infection, showing a lack of ability to replicate and survive within DCs. Additionally we have shown that B. pseudomallei activates DCs, as measured by cytokine secretion, and live bacteria are not required for activation. PMID- 22301614 TI - Qualitative and semiquantitative analysis of Lactobacillus species in the vaginas of healthy fertile and postmenopausal Chinese women. AB - The present study aimed to investigate the prevalence and quantity of Lactobacillus species in the vaginas of healthy Chinese women. Vaginal samples from 92 fertile and 22 postmenopausal healthy Chinese women were analysed using a 16S rRNA gene clone library and species-specific PCR followed by sequencing and real-time PCR. A total of 13 different Lactobacillus species were detected. Species-specific PCR showed that 3% of the fertile women were colonized by one species of Lactobacillus and 97% were colonized by two or more species. Among the postmenopausal women, 91% were colonized by one species of Lactobacillus and 9% were colonized by two species. In the fertile women, L. iners (82.61%), L. crispatus (70.65%) and L. gasseri (67.39%) were more prevalent than L. jensenii (40.22%), L. acidophilus (39.13%), L. brevis (23.91%), L. plantarum (5.43%), L. johnsonii (3.26%), L. fermentum (2.17%), L. salivarius (2.17%), L. rhamnosus (1.09%), L. reuteri (1.09%) and L. paracasei (1.09%); L. delbrueckii was not detected. In the postmenopausal women, L. fermentum, L. rhamnosus, L. reuteri and L. delbrueckii were not detected, and the other 10 species were detected in just a few samples. The prevalence of these species according to the clone library differed from the prevalence indicated by the species-specific PCR. According to the semiquantitative analysis, the total Lactobacillus DNA concentrations were higher in fertile women than in postmenopausal women. Sixty-one per cent of the fertile women were predominantly colonized by L. iners, 35% by L. crispatus, and 2% by L. gasseri. Associations between pairs of Lactobacillus species in fertile women were significant (P<0.05) between the following pairs: L. iners and L. gasseri, L. iners and L. jensenii, L. iners and L. acidophilus, L. gasseri and L. acidophilus, and L. gasseri and L. jensenii. In conclusion, this study provided detailed information on Lactobacillus species colonizing the vaginas of healthy Chinese fertile and postmenopausal women. The study also showed that the diversity of Lactobacillus species in fertile women was higher than in postmenopausal women. According to our study, different techniques, such as species-specific PCR and comparison against a 16S rRNA gene clone library, resulted in different findings regarding species prevalence. These findings highlight the importance of standardization of techniques used for evaluation of bacterial communities. According to our findings regarding species associations, L. iners and L. gasseri may have influences on colonization and proliferation of other vaginal Lactobacillus species. PMID- 22301615 TI - Multidrug-resistant North American pulsotype 2 Clostridium difficile was the predominant toxigenic hospital-acquired strain in the province of Manitoba, Canada, in 2006-2007. AB - The objective of the current study was to determine whether the antimicrobial susceptibility profile or genotype of hospital-acquired isolates of Clostridium difficile differed from isolates causing community-acquired disease. Five hundred diarrhoeal stool samples (one >2 ml sample per patient) from patients across Manitoba, Canada, in 2006-2007 that were reported as C. difficile toxin positive were cultured, resulting in 432 isolates of toxin-positive C. difficile for analysis. Of these 432 isolates, acquisition status could be determined for 235 (54.4%); 182 (77.4%) isolates were hospital acquired and 53 (22.6%) were community acquired. North American pulsotype (NAP) designations based on SmaI PFGE could be defined for 52.3% of the 432 isolates, with NAP2 (n=122) being the most common. Ninety-one per cent (71/78) of NAP2 isolates were recovered from patients with hospital-acquired C. difficile disease. Other NAP types and isolates with non-NAP-type PFGE patterns were less frequently associated with hospital-acquired disease. Community-acquired disease (35.3% of isolates) was associated with a wide variety of NAP types. NAP2 isolates were homogeneous (85.5% had SmaI PFGE pattern 0003) and demonstrated low susceptibility to moxifloxacin (6.6%) and clindamycin (1.6%) compared with non-NAP2 isolates (64.1 93.2% moxifloxacin susceptible; 14.1-28.2% clindamycin susceptible). All isolates of C. difficile in Manitoba were susceptible to metronidazole, piperacillin tazobactam, amoxicillin-clavulanate and meropenem. NAP2 isolates of toxigenic C. difficile were approximately three times more common than NAP1 isolates (28.2 vs 9.1%) in Manitoba in 2006-2007, and these isolates demonstrated high levels of clonality and multidrug resistance, and were associated with hospital acquisition. PMID- 22301616 TI - Persistent Helicobacter pullorum colonization in C57BL/6NTac mice: a new mouse model for an emerging zoonosis. AB - Helicobacter pullorum, an enterohepatic Helicobacter species, is associated with gastroenteritis and hepatobiliary disease in humans and chickens. Recently, a novel H. pullorum outbreak in barrier-maintained rats and mice was described. In this study, persistence of infection and serological responses were further evaluated in H. pullorum-infected female C57BL/6NTac and C3H/HeNTac mice obtained from the barrier outbreak. C57BL/6NTac mice (n=36) aged 10-58 weeks were confirmed to be chronically infected with H. pullorum by PCR or culture of caecum, colon and faeces, with no evidence of hepatic infection; two of three C3H/HeNTac mice cleared H. pullorum infection by 26 weeks of age. A quantitative PCR (qPCR) assay based on the cdtB gene specific to H. pullorum demonstrated that colonization was high in the caecum and colon at 10(4)-10(6) c.f.u. equivalents per ug host DNA, and decreased by several logs from 32 to 58 weeks of age. Infected mice were seropositive by ELISA, and H. pullorum-specific IgG levels decreased as colonization was lost over time in selected mice. Consistent with the lack of pathology associated with chronic infection of C57BL/6 mice with other murine enteric helicobacters, C57BL/6NTac and C3H/HeNTac mice infected with H. pullorum did not develop gross or histological lesions of the liver or gastrointestinal tract. The cdtB-based qPCR assay can be used in screening animals, food sources and environmental samples for H. pullorum, as this food borne pathogen has zoonotic potential. These findings will also allow future studies in murine models to dissect potential pathogenic mechanisms for this emerging pathogen. PMID- 22301617 TI - Garlic ointment inhibits biofilm formation by bacterial pathogens from burn wounds. AB - When thermal injury damages the skin, the physical barrier protecting underlying tissues from invading micro-organisms is compromised and the host's immune system becomes supressed, facilitating colonization and infection of burn wounds with micro-organisms. Within the wound, bacteria often develop biofilms, which protect the bacteria from the immune response and enhance their resistance to antibiotics. As the prophylactic use of conventional antibiotics drives selection of drug-resistant strains, the use of novel agents to prevent biofilm formation by wound pathogens is essential. In the present study, we utilized our recently developed in vitro wound biofilm model to examine the antibiofilm activity of garlic (Allium sativum). Wound pathogens were inoculated on sterile cellulose discs, exposed to formulated garlic ointment (GarO) or ointment base, and incubated to allow biofilm development. Biofilms were quantified and visualized microscopically. GarO prevented biofilm development by Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae, and caused a 2-5 log reduction of the bioburden within Enterococcus faecalis biofilms. Additionally, GarO disrupted partially developed biofilms produced by S. aureus, S. epidermidis and A. baumannii. The antistaphylococcal activity of GarO was stable for over 3 months at room temperature. Thus, GarO could be used as a prophylactic therapy to prevent wound biofilms caused by both Gram-negative and Gram-positive bacteria from forming, and may be a potential therapy for disrupting established staphylococcal biofilms. PMID- 22301618 TI - PERTHESE implant-identical cohesive-gel sizers in breast augmentation: a prospective report on 200 consecutive cases and implications for treatment of breast asymmetry. AB - BACKGROUND: The insertion of sizers in breast augmentation surgery is a common method of predicting the final volume of prosthesis required. However, saline filled sizers may not accurately represent the shape of the cohesive-gel augmented breast. PERTHESE cohesive-gel breast implants are produced with matching sets of reusable (sterilizable) cohesive-gel-filled sizers that accurately predict the form of the augmented breast. OBJECTIVES: The authors assess the efficacy of PERTHESE sizers and implants in 200 consecutive patients who presented for breast augmentation. METHODS: Data were prospectively collected for all patients who underwent bilateral breast augmentation between 2003 and 2010 with the senior author (BGHL), during which time he inserted PERTHESE implants exclusively in his clinical practice. The 200 patients included in this series were analyzed according to demographic details, preoperative findings (including the presence of breast asymmetry), surgical approach, postoperative patient and surgeon satisfaction scores, and complications. RESULTS: Less than 2% of patients in this series experienced complications such as hematoma, seroma formation, or infection. Capsular contracture developed in 7% of patients, but there were no visible or painful capsules. Only 2% of patients elected to undergo surgical revision for aesthetic reasons. A high proportion (87%) of the 27 patients who had significant preoperative breast asymmetry were satisfied with the aesthetic outcome of their surgery. Likewise, a significant percentage (92%) of the 148 patients who had preoperative breast symmetry were satisfied with their outcome. CONCLUSIONS: Application of intraoperative form-stable cohesive gel sizers can enhance the surgeon's ability to predict the final appearance of the augmented breast. The placement of these form-stable sizers and implants is a particular advantage in cases of established breast asymmetry. PMID- 22301619 TI - Inducible kidney-specific Sgk1 knockout mice show a salt-losing phenotype. AB - The expression of the serum- and glucocorticoid-regulated kinase 1 (Sgk1) is induced by mineralocorticoids and, in turn, upregulates the renal epithelial Na(+) channel (ENaC). Total inactivation of Sgk1 has been associated with transient urinary Na(+) wasting with a low-Na(+) diet, while the aldosterone mediated ENaC channel activation was unchanged in the collecting duct. Since Sgk1 is ubiquitously expressed, we aimed to study the role of renal Sgk1 and generated an inducible kidney-specific knockout (KO) mouse. We took advantage of the previously described TetOn/CreLoxP system, in which rtTA is under the control of the Pax8 promotor, allowing inducible inactivation of the floxed Sgk1 allele in the renal tubules (Sgk1fl/fl/Pax8/LC1 mice). We found that under a standard Na(+) diet, renal water and Na(+)/K(+) excretion had a tendency to be higher in doxycycline-treated Sgk1 KO mice compared with control mice. The impaired ability of Sgk1 KO mice to retain Na(+) increased significantly with a low-salt diet despite higher plasma aldosterone levels. On a low-Na(+) diet, the Sgk1 KO mice were also hyperkaliuric and lost body weight. This phenotype was accompanied by a decrease in systolic and diastolic blood pressure. At the protein level, we observed a reduction in phosphorylation of the ubiquitin protein-ligase Nedd4-2 and a decrease in the expression of the Na(+)-Cl(-)-cotransporter (NCC) and to a lesser extent of ENaC. PMID- 22301620 TI - Protein kinase C-alpha mediates hypertonicity-stimulated increase in urea transporter phosphorylation in the inner medullary collecting duct. AB - The UT-A1 urea transporter plays a critical role in the production of concentrated urine. Both vasopressin and hypertonicity increase urea permeability in rat terminal inner medullary collecting ducts (IMCD). Each agonist independently increases UT-A1 phosphorylation and apical plasma membrane accumulation. Vasopressin activates PKA and phosphorylates UT-A1 at serines 486 and 499. Hypertonicity stimulates urea permeability through protein kinase C (PKC) and intracellular calcium. To determine whether the hypertonic stimulation of urea permeability results from a PKC-mediated phosphorylation of UT-A1, rat IMCDs were metabolically labeled with [(32)P]. Hypertonicity stimulated UT-A1 phosphorylation, and this increase was blocked by preincubation with a PKC inhibitor. IMCDs were biotinylated to assess plasma membrane UT-A1. Hypertonicity increased biotinylated UT-A1, and this increase was blocked by preincubation with a PKC inhibitor. When PKC was directly activated using a phorbol ester, total UT A1 phosphorylation increased, but phosphorylation at serine 486 was not increased, indicating that PKC did not phosphorylate UT-A1 at the same residue as PKA. Since PKC-alpha is a calcium-dependent PKC isoform and PKC-alpha knockout mice have a urine-concentrating defect, it suggested that PKC-alpha may mediate the response to hypertonicity. Consistent with this hypothesis, hypertonicity increased phospho-PKC-alpha in rat IMCDs. Finally, PKC-alpha knockout mice were used to determine whether hypertonicity could stimulate UT-A1 phosphorylation in the absence of PKC-alpha. Hypertonicity significantly increased UT-A1 phosphorylation in wild-type mice but not in PKC-alpha knockout mice. We conclude that PKC-alpha mediates the hypertonicity-stimulated increase in UT-A1 phosphorylation in the IMCD. PMID- 22301621 TI - Increased urinary excretion of nephrin, podocalyxin, and betaig-h3 in women with preeclampsia. AB - Emerging evidence has shown that podocyte injury and reduced specific podocyte protein expressions contribute to proteinuria in preeclampsia. We collected urine specimens from women with preeclampsia to study whether podocyte-specific protein shedding is associated with renal barrier dysfunction. Urine specimens from women with normal pregnancies and from pregnant women complicated by chronic hypertension were used for comparison. We determined soluble podocyte slit protein nephrin levels in the urine specimens. Podocalyxin, betaig-h3, and VEGF concentrations were also measured. We found that nephrin and podocalyxin were barely detectable in the urine specimens from normal pregnant women and from women with chronic hypertension. In preeclampsia, urinary nephrin and podocalyxin concentrations were significantly increased and highly correlated to each other, r(2) = 0.595. Nephrin and podocalyxin were also correlated with urine protein concentrations. betaig-h3 was detected in the urine specimens from women with preeclampsia, and it is highly correlated with nephrin and podocalyxin concentrations in preeclampsia. betaig-h3 was undetectable in normal pregnancy and pregnancy complicated by chronic hypertension. Elevated VEGF levels were also found in women with preeclampsia compared with those of normal pregnancy and pregnancy complicated by chronic hypertension. These results provide strong evidence that podocyte protein shedding occurs in preeclampsia, and their levels are associated with proteinuria. The finding of urinary betaig-h3 excretion in preeclampsia suggests that increased transforming growth factor activity might also be involved in the kidney lesion in this pregnancy disorder. PMID- 22301623 TI - Cohesion of epithelial ion homeostasis: implementing calcium transport with sodium transporters? PMID- 22301622 TI - PTEN loss defines a TGF-beta-induced tubule phenotype of failed differentiation and JNK signaling during renal fibrosis. AB - We investigated the signaling basis for tubule pathology during fibrosis after renal injury. Numerous signaling pathways are activated physiologically to direct tubule regeneration after acute kidney injury (AKI) but several persist pathologically after repair. Among these, transforming growth factor (TGF)-beta is particularly important because it controls epithelial differentiation and profibrotic cytokine production. We found that increased TGF-beta signaling after AKI is accompanied by PTEN loss from proximal tubules (PT). With time, subpopulations of regenerating PT with persistent loss of PTEN (phosphate and tension homolog) failed to differentiate, became growth arrested, expressed vimentin, displayed profibrotic JNK activation, and produced PDGF-B. These tubules were surrounded by fibrosis. In contrast, PTEN recovery was associated with epithelial differentiation, normal tubule repair, and less fibrosis. This beneficial outcome was promoted by TGF-beta antagonism. Tubule-specific induction of TGF-beta led to PTEN loss, JNK activation, and fibrosis even without prior AKI. In PT culture, high TGF-beta depleted PTEN, inhibited differentiation, and activated JNK. Conversely, TGF-beta antagonism increased PTEN, promoted differentiation, and decreased JNK activity. Cre-Lox PTEN deletion suppressed differentiation, induced growth arrest, and activated JNK. The low-PTEN state with JNK signaling and fibrosis was ameliorated by contralateral nephrectomy done 2 wk after unilateral ischemia, suggesting reversibility of the low-PTEN dysfunctional tubule phenotype. Vimentin-expressing tubules with low-PTEN and JNK activation were associated with fibrosis also after tubule-selective AKI, and with human chronic kidney diseases of diverse etiology. By preventing tubule differentiation, the low-PTEN state may provide a platform for signals initiated physiologically to persist pathologically and cause fibrosis after injury. PMID- 22301624 TI - Computer simulations of osmotic ultrafiltration and small-solute transport in peritoneal dialysis: a spatially distributed approach. AB - The aim of this study was to simulate clinically observed intraperitoneal kinetics of dialysis fluid volume and solute concentrations during peritoneal dialysis. We were also interested in analyzing relationships between processes in the peritoneal cavity and processes occurring in the peritoneal tissue and microcirculation. A spatially distributed model was formulated for the combined description of volume and solute mass balances in the peritoneal cavity and flows across the interstitium and the capillary wall. Tissue local parameters were assumed dependent on the interstitial hydration and vasodilatation induced by glucose. The model was fitted to the average volume and solute concentration profiles from dwell studies in 40 clinically stable patients on chronic ambulatory peritoneal dialysis using a 3.86% glucose dialysis solution. The model was able to describe the clinical data with high accuracy. An increase in the local interstitial pressure and tissue hydration within the distance of 2.5 mm from the peritoneal surface of the tissue was observed. The penetration of glucose into the tissue and removal of urea, creatinine, and sodium from the tissue were restricted to a layer located within 2 mm from the peritoneal surface. The initial decline of sodium concentration (sodium dip) was observed not only in intraperitoneal fluid but also in the tissue. The distributed model can provide a precise description of the relationship between changes in the peritoneal tissue and intraperitoneal dialysate volume and solute concentration kinetics. Computer simulations suggest that only a thin layer of the tissue within 2-3 mm from the peritoneal surface participates in the exchange of fluid and small solutes between the intraperitoneal dialysate and blood. PMID- 22301625 TI - Angiotensin II regulates growth of the developing papillas ex vivo. AB - We tested the hypothesis that lack of angiotensin (ANG) II production in angiotensinogen (AGT)-deficient mice or pharmacologic antagonism of ANG II AT(1) receptor (AT(1)R) impairs growth of the developing papillas ex vivo, thus contributing to the hypoplastic renal medulla phenotype observed in AGT- or AT(1)R-null mice. Papillas were dissected from Hoxb7(GFP+) or AGT(+/+), (+/-), ( /-) mouse metanephroi on postnatal day P3 and grown in three-dimentional collagen matrix gels in the presence of media (control), ANG II (10(-5) M), or the specific AT(1)R antagonist candesartan (10(-6) M) for 24 h. Percent reduction in papillary length was attenuated in AGT(+/+) and in AGT(+/-) compared with AGT(-/ ) (-18.4 +/- 1.3 vs. -32.2 +/- 1.6%, P < 0.05, -22.8 +/- 1.3 vs. -32.2 +/- 1.6%, P < 0.05, respectively). ANG II blunted the decrease in papilla length observed in respective media-treated controls in Hoxb7(GFP+) (-1.5 +/- 0.3 vs. -10.0 +/- 1.4%, P < 0.05) or AGT(+/+), (+/-), and (-/-) papillas (-12.8 +/- 0.7 vs. -18.4 +/- 1.3%, P < 0.05, -16.8 +/- 1.1 vs. -23 +/- 1.2%, P < 0.05; -26.2 +/- 1.6 vs. 32.2 +/- 1.6%, P < 0.05, respectively). In contrast, percent decrease in the length of Hoxb7(GFP+) papillas in the presence of the AT(1)R antagonist candesartan was higher compared with control (-24.3 +/- 2.1 vs. -10.5 +/- 1.8%, P < 0.05). The number of proliferating phospho-histone H3 (pH3)-positive collecting duct cells was lower, whereas the number of caspase 3-positive cells undergoing apoptosis was higher in candesartan- vs. media-treated papillas (pH3: 12 +/- 1.4 vs. 21 +/- 2.1, P < 0.01; caspase 3: 3.8 +/- 0.5 vs. 1.7 +/- 0.2, P < 0.01). Using quantitative RT-PCR, we demonstrate that AT(1)R signaling regulates the expression of genes implicated in morphogenesis of the renal medulla. We conclude that AT(1)R prevents shrinkage of the developing papillas observed ex vivo via control of Wnt7b, FGF7, beta-catenin, calcineurin B1, and alpha3 integrin gene expression, collecting duct cell proliferation, and survival. PMID- 22301626 TI - Role of cyclooxygenase-1-mediated prostacyclin synthesis in endothelium-dependent vasoconstrictor activity of porcine interlobular renal arteries. AB - This study aimed to determine whether PGI(2) would be evoked by the endogenous endothelial B(2) receptor agonist bradykinin (BK) in the porcine interlobular renal artery and, if so, to determine how it would influence the vasomotor reaction, and the specific cyclooxygenase (COX) isoform(s) involved in its synthesis. The production of the PGI(2) metabolite 6-keto-PGF(1alpha) was analyzed with HPLC-mass spectroscopy, while vasomotor reaction to PGI(2) or BK was determined with isometric force measurement. Results showed that BK evoked an increase in the production of 6-keto-PGF(1alpha), which was abolished by endothelial denudation that removed COX-1 expression, or was reduced by COX-1 inhibition. Interestingly, PGI(2) evoked a potent contraction, which was prevented by antagonizing thromboxane-prostanoid (TP) receptors and was not enhanced by antagonizing the vasodilator PGI(2) (IP) receptors. The IP receptor agonists MRE-269 and iloprost did not induce any relaxation. Moreover, iloprost, which is also a PGI(2) analog, caused a contraction, which was sensitive to TP receptor antagonism, but was to a significantly lesser extent than that of PGI(2). Indeed, IP receptors were not detected by RT-PCR or Western blotting in the vessel. Following nitric oxide synthase (NOS) inhibition, BK also evoked an endothelium-dependent contraction, which was blocked by TP receptor antagonism. In addition, inhibition of COX-1 (but not COX-2) impeded the vasoconstrictor activity of BK and expedited the relaxation induced by the agonist in NOS-intact vessels. These results demonstrate that in the porcine interlobular renal artery BK evokes endothelial COX-1-mediated PGI(2) synthesis, which mainly leads to the activation of TP receptors and a vasoconstrictor response, possibly due to a scarcity of vasodilator activity mediated by IP receptors. Also, our data suggested that the effect of a PGI(2) analog on TP receptors could be reduced compared with that of PGI(2) due to modified structure as with iloprost. PMID- 22301627 TI - Cardenolides and bufadienolides as hormones: what is missing? PMID- 22301628 TI - Combined inhibition of aromatase activity and dihydrotestosterone supplementation attenuates renal injury in male streptozotocin (STZ)-induced diabetic rats. AB - Our previous studies showed that streptozotocin (STZ)-induced diabetic male rats have increased estradiol and decreased testosterone levels that correlate with renal injury (Xu Q, Wells CC, Garman GH, Asico L, Escano CS, Maric C. Hypertension 51: 1218-1224, 2008). We further showed that either supplementing dihydrotestosterone (DHT) or inhibiting estradiol biosynthesis in these diabetic rats was only partially renoprotective (Manigrasso MB, Sawyer RT, Marbury DC, Flynn ER, Maric C. Am J Physiol Renal Physiol 301: F634-F640, 2011; Xu Q, Prabhu A, Xu S, Manigrassso MB, Maric C. Am J Physiol 297: F307-F315, 2009). The aim of this study was to test the hypothesis that the combined therapy of DHT supplementation and inhibition of estradiol synthesis would afford better renoprotection than either treatment alone. The study was performed in 12-wk-old male nondiabetic (ND), STZ-induced diabetic (D), and STZ-induced diabetic rats that received the combined therapy of 0.75 mg/day of DHT along with 0.15 mg . kg( 1) . day(-1) of an aromatase inhibitor, anastrozole (Dta), for 12 wk. Treatment with the combined therapy resulted in attenuation of albuminuria by 84%, glomerulosclerosis by 55%, and tubulointerstitial fibrosis by 62%. In addition, the combined treatment decreased the density of renal cortical CD68-positive cells by 70% and decreased protein expression of transforming growth factor-beta protein expression by 60%, collagen type IV by 65%, TNF-alpha by 55%, and IL-6 by 60%. We conclude that the combined treatment of DHT and blocking aromatase activity in diabetic male STZ-induced diabetic rats provides superior treatment than either treatment alone in the prevention of diabetic renal disease. PMID- 22301631 TI - The identification of gene duplication and the role of secreted aspartyl proteinase 1 in Candida parapsilosis virulence. AB - In this study, we analyzed the role of Candida parapsilosis-secreted aspartyl proteinase isoenzyme 1 (SAPP1) in virulence. The in silico analysis of SAPP1 sequence revealed a 2871 base pair-duplicated region (SAPP1a and SAPP1b) in the genome of C. parapsilosis. We generated homozygous DeltaDeltasapp1a, DeltaDeltasapp1b, and DeltaDeltasapp1a-DeltaDeltasapp1b mutants. Notably, Sapp1 production in an inducer medium was reduced by approximately 50% in the DeltaDeltasapp1a and DeltaDeltasapp1b mutants, but the other validated SAPP gene (SAPP2) was not affected. In contrast, Sapp2 production was increased in the DeltaDeltasapp1a-DeltaDeltasapp1b mutant relative to wild-type (WT) yeast. The DeltaDeltasapp1a-DeltaDeltasapp1b strain was hypersusceptible to human serum and was attenuated in its capacity to damage host-effector cells. The phagocytosis and killing of DeltaDeltasapp1a-DeltaDeltasapp1b yeasts by human peripheral blood mononuclear cells (PBMCs) and PBMC-derived macrophages (PBMC-DM) was significantly enhanced relative to WT. Phagolysosomal fusion in PBMC-DMs occurred more than twice as frequently with ingested DeltaDeltasapp1a-DeltaDeltasapp1b yeast cells compared with WT. PMID- 22301630 TI - Therapeutic vaccination with recombinant adenovirus reduces splenic parasite burden in experimental visceral leishmaniasis. AB - Therapeutic vaccines, when used alone or in combination therapy with antileishmanial drugs, may have an important place in the control of a variety of forms of human leishmaniasis. Here, we describe the development of an adenovirus based vaccine (Ad5-KH) comprising a synthetic haspb gene linked to a kmp11 gene via a viral 2A sequence. In nonvaccinated Leishmania donovani-infected BALB/c mice, HASPB- and KMP11-specific CD8(+) T cell responses were undetectable, although IgG1 and IgG2a antibodies were evident. After therapeutic vaccination, antibody responses were boosted, and IFNgamma(+)CD8(+) T cell responses, particularly to HASPB, became apparent. A single vaccination with Ad5-KH inhibited splenic parasite growth by ~66%, a level of efficacy comparable to that observed in early stage testing of clinically approved antileishmanial drugs in this model. These studies indicate the usefulness of adenoviral vectors to deliver leishmanial antigens in a potent and host protective manner to animals with existing L. donovani infection. PMID- 22301632 TI - Impaired fitness of Mycobacterium africanum despite secretion of ESAT-6. AB - BACKGROUND: When compared with Mycobacterium tuberculosis, individuals that live in the same household as an active case of smear-positive pulmonary tuberculosis exposed to M. africanum progress less frequently to active disease within 2 years. A putative ESX-1 secretion apparatus member, Rv3879c, is mutated in M. africanum, and individuals infected with M. africanum less frequently demonstrate T-cell responses to the ESX-1-secreted virulence factor ESAT-6 than those infected with M. tuberculosis. We hypothesized that less frequent progression is caused by impaired secretion of ESAT-6. METHODS: We analyzed in vivo growth and in vitro secretion of ESAT-6 and CFP-10, comparing M. tuberculosis to M. africanum and a strain of M. africanum complemented with M. tuberculosis Rv3879c. RESULTS: ESAT-6 and CFP-10 secretion were similar for all strains, although these were enriched in M. africanum cell lysates, suggesting a modest ESX-1 secretion defect unrelated to the Rv3879c mutation. In mice, M. africanum demonstrated smaller bacterial population sizes than M. tuberculosis but similar numbers and frequencies of ESAT-6-responsive T cells in the lungs. CONCLUSIONS: These results confirm impaired fitness of M. africanum in vivo and indicate that Rv3879c is not required for secretion of ESAT-6 or for its presentation as an antigen to T cells in vivo. PMID- 22301633 TI - Toll-like receptor 1 polymorphisms increase susceptibility to candidemia. AB - BACKGROUND: Candidemia is a severe invasive fungal infection with high mortality. Recognition of Candida species is mediated through pattern recognition receptors such as Toll-like receptors (TLRs). This study assessed whether genetic variation in TLR signaling influences susceptibility to candidemia. METHODS: Thirteen mostly nonsynonymous single nucleotide polymorphisms (SNPs) in genes encoding TLRs and signaling adaptors MyD88 and Mal/TIRAP were genotyped in 338 patients (237 white, 93 African American, 8 other race) with candidemia and 351 noninfected controls (263 white, 88 African American). The SNPs significant in univariate analysis were further analyzed with multivariable logistic regression to determine association with clinical outcomes. Functional consequences of these polymorphisms were assessed via in vitro stimulation assays. RESULTS: Analyses of TLR SNPs revealed that 3 TLR1 SNPs (R80T, S248N, I602S) were significantly associated with candidemia susceptibility in whites. This association was not found in African Americans, likely due to lower power in this smaller study population. Furthermore, these TLR1 polymorphisms displayed impaired cytokine release by primary monocytes. No associations with susceptibility to candidemia were observed for SNPs in TLR2, TLR4, TLR6, TLR9, MyD88, or TIRAP. CONCLUSIONS: Nonsynonymous SNPs in TLR1 are associated with impaired TLR1 function, decreased cytokine responses, and predisposition to candidemia in whites. PMID- 22301634 TI - Age of infection and risk of virally associated cancers: new clues to an old puzzle. PMID- 22301635 TI - Early age at time of primary Epstein-Barr virus infection results in poorly controlled viral infection in infants from Western Kenya: clues to the etiology of endemic Burkitt lymphoma. AB - BACKGROUND: Infection with Epstein-Barr virus (EBV) early in life and repeated malaria exposure have been proposed as risk factors for endemic Burkitt lymphoma (eBL). METHODS: Infants were enrolled from 2 rural sites in Kenya: the Kisumu District, where malaria transmission is holoendemic and risk for eBL is high, and the Nandi District, where malaria transmission is limited and the risk for eBL is low. Blood samples were taken from infants through 2 years of age to measure EBV viral load, EBV antibodies, and malaria parasitemia. RESULTS: We observed a significantly younger age at time of primary EBV infection in children from Kisumu compared with children from Nandi (mean age, 7.28 months [+/-0.33 SEM] in Kisumu vs 8.39 months [+/-0.26 SEM] in Nandi), with 35.3% of children in Kisumu infected before 6 months of age. To analyze how different predictors affected EBV viral load over time, we performed multilevel mixed modeling. This modeling revealed that residence in Kisumu and younger age at first EBV infection were significant predictors for having a higher EBV viral load throughout the period of observation. CONCLUSIONS: Children from a region at high risk for eBL were infected very early in life with EBV, resulting in higher viral loads throughout infancy. PMID- 22301636 TI - Assessment of vertical root fractures using three imaging modalities: cone beam CT, intraoral digital radiography and film. AB - OBJECTIVES: The aim of this study was to assess the accuracy of cone beam CT (CBCT) in detecting vertical root fractures and to compare the accuracy with images from an intraoral sensor and from conventional intraoral film. METHODS: 60 extracted, single-rooted human teeth were divided equally into two groups: a control group of 30 teeth and an induced fracture group of 30 teeth. All teeth were randomly placed into sockets in six dry mandibles. Each tooth was imaged by three modalities: CBCT, intraoral digital radiography and intraoral F-speed film. Three beam angulations (an orthogonal projection and additional projections with +/- 20 degrees horizontal shifts of the central ray) were used when radiographs were made using film and a digital sensor. Three oral and maxillofacial radiologists evaluated the presence of root fractures twice in each image modality using a five-point confidence rating scale. Areas under receiver operating characteristic curves (A(z)) were computed for each observer and modality and were tested for statistical differences using the Kruskal-Wallis test. RESULTS: There was no statistical difference in the performance of the three modalities (mean of A(z) values: CBCT = 0.811, film = 0.797 and sensor = 0.775; p = 0.771). CONCLUSIONS: There was no significant difference between intraoral film, a high-resolution complementary metal oxide semiconductor digital imaging system and CBCT in detecting vertical root fractures in mandibular single rooted teeth. PMID- 22301637 TI - Recurrent keratocystic odontogenic tumours: report of 19 cases. AB - OBJECTIVES: The aim of this study was to analyse 19 recurrent keratocystic odontogenic tumours (KCOTs). METHODS: 19 patients with recurrent KCOTs were retrospectively analysed. These patients had been treated by either enucleation or a combination of enucleation and Carnoy's solution. The analyses covered major aspects of primary KCOT and/or recurrent KCOT identities, including patient profile, clinical features, histopathology, radiology, treatment and prognosis. RESULTS: 19 (7.4%) out of 257 primary KCOT cases recurred, with an average patient age of 30.5 years (age range 18-45 years). 15 lesions were in the mandible and the remaining 4 were in the maxilla. There were more unilocular than multilocular occurrences for the primary tumours, with a ratio of 2.2:1. These KCOTs were initially treated by simple enucleation (12 cases) or enucleation with Carnoy's solution (7 cases). After the initial surgery, 15 out of 19 (78.9%) recurred within 6 years, while 4 (21.1%) recurred after 6 years. Evidently, the recurrent lesion was involved with the roots of the teeth in three out of six cases whose teeth were preserved. In addition, the recurrent KCOTs had a tendency to be more multilocular or multifocal than the primary cases, with a unilocular to-multilocular ratio of 1.1:1. CONCLUSIONS: 7.4% of primary KCOTs recurred within 6 years after initial treatment with either enucleation or a combination of enucleation and Carnoy's solution. The recurrent KCOTs were more likely to be multilocular or multifocal than the primary cases and often involved the teeth. The method of operation for these recurrent lesions would be considered as a more aggressive approach. PMID- 22301638 TI - Comparative study between conventional and cone beam CT-synthesized half and total skull cephalograms. AB - OBJECTIVES: The aim of this study was to compare cephalometric measurements obtained from conventional cephalograms with total and half-skull synthesized cone beam CT (CBCT) cephalograms. METHODS: Cephalometric analyses of 30 clinically symmetric patients were conducted by a calibrated examiner on conventional and CBCT-synthesized cephalograms (total, right and left). Reproducibility was investigated using the intraclass correlation coefficient (ICC). The Bland-Altman analysis was used to assess the agreement of the measurements from each factor obtained by conventional, total, right and left CBCT-synthesized cephalograms. RESULTS: The ICC was above 0.9 for most of the 40 cephalometric factors analysed, revealing similar levels of reproducibility. When the measurements obtained from conventional and CBCT-synthesized cephalograms were compared, the Bland-Altman analysis showed a strong agreement between them. CONCLUSIONS: Half-skull CBCT-synthesized cephalograms offer the same diagnostic performance and equivalent reproducibility in terms of cephalometric analysis as observed in conventional and total CBCT-synthesized cephalograms. PMID- 22301639 TI - Perineural spread of adenoid cystic carcinoma in the oral and maxillofacial regions: evaluation with contrast-enhanced CT and MRI. AB - OBJECTIVES: The objective of this study was to compare the accuracy of contrast enhanced CT (CECT) and contrast-enhanced MRI (CEMRI) in the detection of perineural spread (PNS) of adenoid cystic carcinoma (ACC) in the oral and maxillofacial regions. METHODS: This study consisted of 13 ACCs from 13 patients, all of which were histopathologically diagnosed. Both CECT and CEMRI were performed in all patients before the treatment. The images of each patient were retrospectively evaluated for the detection of PNS. The definitions of PNS included abnormal density/signal intensity, contrast enhancement or widening of the pterygopalatine fossa, palatine foramen, incisive canal, mandibular foramen and mandibular canal, and enlargement or excessive contrast enhancement of a nerve. RESULTS: 11 out of 13 cases were proven to exhibit PNS histopathologically. 8 of the 11 cases for which PNS was histopathologically proven exhibited PNS on MR images. Six of the eight cases for which PNS was exhibited on MR images also exhibited PNS on CT images. The sensitivity, specificity and accuracy for the detection of PNS were 55%, 100% and 62% on CT images and 73%, 100% and 77% on MR images, respectively. Although the accuracy of PNS on MR images was slightly superior to that on CT images, there were no statistically significant differences between the detection of PNS on CT images and on MR images. CONCLUSIONS: CT and MR images are equally useful for the detection of PNS of ACC in the oral and maxillofacial regions. PMID- 22301640 TI - Compliance of Iranian dentists with safety standards of oral radiology. AB - OBJECTIVES: Dentists use radiographs in their daily practice. Their knowledge and behaviour towards radiographic examination can affect patients' exposure to radiation. The aim of this study was to survey the knowledge and behaviour of Iranian dentists regarding oral radiology safety standards. METHODS: 1000 questionnaires were given to the participants of the 48th Annual Congress of the Iranian Dental Association, of which 700 were returned. The participants were asked about demographic data, primary knowledge of radiation protection, selection criteria, radiographic equipment and technique, methods of patient and personnel protection and management of radiographic waste. Descriptive analysis of data was performed. RESULTS: 44% of respondents said the initial radiograph they took was of the periapical view of a limited area. 12% preferred the periapical paralleling technique. F-speed film was used by 9% and E-speed film by 62%. Only 2% had digital receptors. Proper exposure time was selected by 26.5%. The use of long and rectangular collimators was 15% and 6%, respectively. 34% occasionally covered their patients with both thyroid shields and lead aprons. 36% used the position and distance rule correctly for their own protection. Proper disposal of the used processing solutions and the lead foils were done by only 1% and 3%, respectively. CONCLUSIONS: It can be concluded that the majority of dentists in the study group did not select the proper method, material and equipment in order to minimize the exposure of their patient to unnecessary radiation in dental radiography. PMID- 22301641 TI - Central giant cell granulomas: a systematic review of the radiographic characteristics with the addition of 20 new cases published in Dentomaxillofacial Radiology 2002; 31: 213-217. PMID- 22301644 TI - Ectocarpus: a model organism for the brown algae. AB - The brown algae are an interesting group of organisms from several points of view. They are the dominant organisms in many coastal ecosystems, where they often form large, underwater forests. They also have an unusual evolutionary history, being members of the stramenopiles, which are very distantly related to well-studied animal and green plant models. As a consequence of this history, brown algae have evolved many novel features, for example in terms of their cell biology and metabolic pathways. They are also one of only a small number of eukaryotic groups to have independently evolved complex multicellularity. Despite these interesting features, the brown algae have remained a relatively poorly studied group. This situation has started to change over the last few years, however, with the emergence of the filamentous brown alga Ectocarpus as a model system that is amenable to the genomic and genetic approaches that have proved to be so powerful in more classical model organisms such as Drosophila and Arabidopsis. PMID- 22301645 TI - Antibody staining of the central nervous system in adult Drosophila. AB - The Drosophila nervous system provides a valuable model for studying various aspects of brain development and function. The postembryonic Drosophila brain is especially useful, because specific neuron types derive from specific progenitors at specific times. Elucidating the means by which diverse neuron types derive from a limited number of progenitors can contribute significantly to our understanding of the genetic and molecular mechanisms involved in developmental neurobiology. Antibody-labeling techniques are particularly useful for examining the Drosophila brain. These methods generally use primary antibodies specific to a protein or a structure of interest and a fluorescently labeled or enzyme coupled secondary antibody to detect the primary antibodies. Immunofluorescence methods allow for simultaneous probing for multiple antigens using different fluorophores, as well as high-resolution confocal examination of deep structures. This protocol describes general procedures for antibody labeling of neural tissue from Drosophila, as well as visualization techniques for fluorescent and enzyme linked probes. PMID- 22301646 TI - X-gal staining of the central nervous system in adult Drosophila. AB - The Drosophila nervous system provides a valuable model for studying various aspects of brain development and function. The postembryonic Drosophila brain is especially useful, because specific neuron types derive from specific progenitors at specific times. Elucidating the means by which diverse neuron types derive from a limited number of progenitors can contribute significantly to our understanding of the genetic and molecular mechanisms involved in developmental neurobiology. beta-Galactosidase, the product of the E. coli lacZ gene, has been used extensively as a reporter in Drosophila research. Staining for beta galactosidase activity can be performed using the substrate X-gal (5-bromo-4 chloro-3-indolyl-beta-D-galactopyranoside), which produces a blue precipitate visible by light microscopy. This detection method is highly sensitive and has the advantage that the results can be observed without the need for specialized microscopy equipment. This protocol describes general procedures for X-gal labeling of neural tissue from Drosophila. PMID- 22301647 TI - Hydroxyurea ablation of mushroom bodies in Drosophila. AB - Chemical ablation is an effective tool for studying nervous system development and function in Drosophila. Hydroxyurea (HU) inhibits ribonucleotide reductase, blocking DNA synthesis, and killing dividing cells. The specificity of HU ablation is thus dependent on developmental events. In this respect, HU is useful in determining temporal patterns of neuroblast proliferation and the origins of neuronal elements in flies and other insects. In Drosophila, an especially fortuitous time window occurs at the end of embryonic development. For the first 8-12 h after larval hatching, only five neuroblasts are proliferating in each brain hemisphere. Four of these are found in the dorsal protocerebrum and give rise to the intrinsic elements (Kenyon cells [KCs] and glia) of the mushroom bodies (MBs). The remaining single neuroblast has an anterolateral position in the brain and is the progenitor of local interneurons (LocI) in the antennal lobe (AL) and a subset of lateral relay interneurons (RIl) in the inner antennocerebral tract (iACT). Treating newly hatched larvae with HU results in adult flies with KCs and AL interneurons of embryonic origin only. This protocol describes methods for collecting newly hatched Drosophila larvae and treating them with HU. PMID- 22301648 TI - Experimental methods for examining synaptic plasticity in Drosophila. AB - The Drosophila neuromuscular junction (NMJ) ranks as one of the preeminent model systems for studying synaptic development, function, and plasticity. In this article, we review the experimental genetic methods that include the use of mutated or reengineered ion channels to manipulate the synaptic connections made by motor neurons onto larval body-wall muscles. We also provide a consideration of environmental and rearing conditions that phenocopy some of the genetic manipulations. PMID- 22301649 TI - Monitoring membrane excitability in Drosophila expressing modified shaker constructs. AB - The Drosophila neuromuscular junction (NMJ) ranks as one of the preeminent model systems for studying synaptic development, function, and plasticity. This protocol describes the use of the two-electrode voltage clamp (TEVC) to examine potassium (K(+)) currents mediated by voltage-gated ion channels, and gives several genetic and pharmacological methods that are used to study the currents. Drosophila larval muscle fibers possess three major K(+) currents. One of these, a fast voltage-activating and inactivating I(A) current, is mediated by the Shaker channel. The Shaker channel is characterized by its sensitivity to the drug 4-aminopyridine (4-AP). Two useful transgenic tools for altering membrane excitability have been developed by making specific modifications of the Shaker channel; their use is described here. PMID- 22301650 TI - Genetic analysis: moving between linkage and association. AB - The approaches to identifying genes and genomic regions associated with human disease can be grouped into two categories: linkage analysis and genetic association analysis. Linkage analysis is useful for diseases of high penetrance that run strongly within families, but is limited in its ability to detect situations where there are multiple genes with smaller effects. An alternative is genetic association studies, which were initially performed on small numbers of candidate genes. This approach identified relatively few genes that were consistently associated with disease, but it is now possible to do a genetic association for the whole genome, making this approach more powerful. In practice, the two types of analysis are often interlinked. This article provides information on the tools needed to perform both genetic linkage and genetic association analysis. PMID- 22301651 TI - Synapto-pHluorins: genetically encoded reporters of synaptic transmission. AB - pHluorins are pH-sensitive mutants of green fluorescent protein (GFP). Attached to proteins with defined cellular locations or itineraries, pHluorins report subcellular pH as well as protein transport between compartments of differing pH. Key applications in neurobiology include the optical detection of neurotransmitter release with synapto-pHluorins and their derivatives, as well as measurements of neurotransmitter receptor trafficking. This article describes the properties and uses of synapto-pHluorins, as well as their advantages and limitations. PMID- 22301652 TI - Fiber-optic calcium monitoring of dendritic activity in vivo. AB - Observing dendritic activity in active animals presents great challenges and there are currently not many options available. This protocol describes the fiber optic-based "periscope" method for recording from populations of layer 5 (L5) neocortical pyramidal dendrites. This is an inexpensive, convenient, and robust method for recording dendritic activity during behavior. The limitations of this approach are discussed and tips are provided for how it might be adapted for different purposes and brain areas. PMID- 22301653 TI - Three-dimensional morphology and gene expression mapping for the Drosophila blastoderm. AB - To properly understand the transcriptional network of animals, we must have full quantitative comprehension of the spatial and temporal expression patterns of transcription factors and their targets. Visual inspection of embryos stained to reveal the patterns of genes shows levels of expression that change from cell to cell in a complex manner. With our current wealth of knowledge regarding the basic biology of animal genomes and the components of their transcriptional regulatory networks, combined with current technologies in optical microscopy, computing, and image and vision analysis, we should be able to capture quantitative, three-dimensional (3D) information about the transcriptional network (all factors and targets) for an entire animal at cellular resolution. It should also be possible to assemble these data into a single computationally analyzable database--an atlas--that could be the basis for uncovering new biology governing regulatory gene networks. This article describes progress toward realizing these goals, with the focus on Drosophila melanogaster. It describes a suite of high-throughput methods that have been used to create the first quantitative 3D description of gene expression and morphology at cellular resolution in a whole animal, and it presents some of the new biology that has been revealed by this quantitative atlas. PMID- 22301654 TI - Using cultured mammalian cells to study mitosis. AB - Diverse cell types have been used to study various aspects of mitosis. Early investigators focused primarily on cells that were suited to morphological studies. More recently, experimental systems have been developed to study both morphology and the molecular basis of chromosome motion and cell-cycle regulation. This article briefly reviews cell types that have been used to study mitosis in live cells. It then discusses cell lines that have been used to examine mitosis in cultured mammalian cells and summarizes the methods that are used to culture and study these cells. PMID- 22301655 TI - Synthesis of linear polyethylenimine and use in transfection. AB - Linear polyethylenimine (LPEI) is an efficient transfection reagent for a broad range of cell lines and primary cells and is also useful for local or systemic gene delivery in vivo. In contrast to many other nonviral transfection methods, LPEI is less dependent on mitosis and also transfects postmitotic cells. Transfections can be performed with a simple protocol, as described here. The presence of serum (up to 10%) during transfection does not markedly decrease transfection efficiency, but it significantly reduces toxicity, especially to primary cells. This is a major advantage compared to most lipidic transfection systems. Toxicity can also be kept to a minimum using low, optimized amounts of the transfection reagent. However, LPEI can be quite toxic when applied at elevated doses in vitro or in vivo. LPEI is a fully synthetic product that can be easily synthesized from rather inexpensive precursors and is suitable for large scale transfections. This protocol describes the synthesis of LPEI from a precursor polymer and the generation of DNA/LPEI polyplexes. Transfection protocols for cells adherent to tissue culture dishes or grown in suspension are given, as are in vivo applications. PMID- 22301656 TI - Design and construction of 2A peptide-linked multicistronic vectors. AB - The need for reliable, multicistronic vectors for multigene delivery is at the forefront of biomedical technology. This article describes the design and construction of 2A peptide-linked multicistronic vectors, which can be used to express multiple proteins from a single open reading frame (ORF). The small 2A peptide sequences, when cloned between genes, allow for efficient, stoichiometric production of discrete protein products within a single vector through a novel "cleavage" event within the 2A peptide sequence. Expression of more than two genes using conventional approaches has several limitations, most notably imbalanced protein expression and large size. The use of 2A peptide sequences alleviates these concerns. They are small (18-22 amino acids) and have divergent amino-terminal sequences, which minimizes the chance for homologous recombination and allows for multiple, different 2A peptide sequences to be used within a single vector. Importantly, separation of genes placed between 2A peptide sequences is nearly 100%, which allows for stoichiometric and concordant expression of the genes, regardless of the order of placement within the vector. PMID- 22301657 TI - Generation of 2A-linked multicistronic cassettes by recombinant PCR. AB - The need for reliable, multicistronic vectors for multigene delivery is at the forefront of biomedical technology. It is now possible to express multiple proteins from a single open reading frame (ORF) using 2A peptide-linked multicistronic vectors. These small sequences, when cloned between genes, allow for efficient, stoichiometric production of discrete protein products within a single vector through a novel "cleavage" event within the 2A peptide sequence. Expression of more than two genes using conventional approaches has several limitations, most notably imbalanced protein expression and large size. The use of 2A peptide sequences alleviates these concerns. They are small (18-22 amino acids) and have divergent amino-terminal sequences, which minimizes the chance for homologous recombination and allows for multiple, different 2A peptide sequences to be used within a single vector. Importantly, separation of genes placed between 2A peptide sequences is nearly 100%, which allows for stoichiometric and concordant expression of the genes, regardless of the order of placement within the vector. This protocol describes the use of recombinant polymerase chain reaction (PCR) to connect multiple 2A-linked protein sequences. The final construct is subcloned into an expression vector. PMID- 22301658 TI - Verification of 2A peptide cleavage. AB - The need for reliable, multicistronic vectors for multigene delivery is at the forefront of biomedical technology. It is now possible to express multiple proteins from a single open reading frame (ORF) using 2A peptide-linked multicistronic vectors. These small sequences, when cloned between genes, allow for efficient, stoichiometric production of discrete protein products within a single vector through a novel "cleavage" event within the 2A peptide sequence. The easiest and most effective way to assess 2A cleavage is to perform transient transfection of 293T cells (human embryonic kidney cells) followed by western blot analysis, as described in this protocol. 293T cells are easy to grow and can be efficiently transfected with a variety of vectors. Cleavage can be assessed by detection with antibodies against the target proteins or anti-2A serum. PMID- 22301659 TI - Experimental strategies for cloning or identifying genes encoding DNA-binding proteins. AB - This article describes experimental strategies for cloning or identifying genes encoding DNA-binding proteins. DNA-binding proteins are most commonly identified by electrophoretic mobility-shift assay (EMSA) or DNase I footprinting. To identify the gene encoding a protein detected by EMSA or DNase footprinting, the protein often needs to be purified and its sequence analyzed, as described here. Other methods are also available which do not resort to protein purification, including the one-hybrid screen, in vitro expression library screen, and mammalian expression cloning. These methods are outlined, and their advantages and disadvantages are discussed. PMID- 22301660 TI - Colocalization of fluorescent probes: accurate and precise registration with nanometer resolution. AB - Colocalization of fluorescent probes is commonly used in cell biology to discern the proximity of two proteins in the cell. Considering that the resolution limit of optical microscopy is on the order of 250 nm, there has not been a need for high-resolution colocalization techniques. However, with the advent of higher resolution techniques for cell biology and single-molecule biophysics, colocalization must also improve. For diffraction-limited applications, a geometric transformation (i.e., translation, scaling, and rotation) is typically applied to one color channel to align it with the other; however, to achieve high resolution colocalization, this is not sufficient. Single-molecule high resolution colocalization (SHREC) of single probes uses the local weighted mean transformation to achieve a colocalization resolution of at least 10 nm. This article describes the process of collecting a calibration data set of fiducials and the appropriate analysis to determine the transformation for colocalization. PMID- 22301661 TI - Single-molecule high-resolution colocalization of single probes. AB - Colocalization of fluorescent probes is commonly used in cell biology to discern the proximity of two proteins in the cell. Considering that the resolution limit of optical microscopy is on the order of 250 nm, there has not been a need for high-resolution colocalization techniques. However, with the advent of higher resolution techniques for cell biology and single-molecule biophysics, colocalization must also improve. For diffraction-limited applications, a geometric transformation (i.e., translation, scaling, and rotation) is typically applied to one color channel to align it with the other; however, to achieve high resolution colocalization, this is not sufficient. Single-molecule high resolution colocalization (SHREC) of single probes uses the local weighted mean transformation to achieve a colocalization resolution of at least 10 nm. This protocol describes the acquisition of registration data and the analysis required to obtain a high-resolution mapping between imaging channels. The total internal reflection fluorescence microscope (TIRFM) system described is designed to excite and image the fluorescent probes Cy3 and Cy5. Modifications may be required depending on the requirements of the individual study. PMID- 22301662 TI - How to cultivate Ectocarpus. AB - This article describes the standard procedure for growing Ectocarpus in the laboratory. The culture is started with partheno-sporophyte (or sporophyte) filaments because this is the stage that is usually maintained in strain collections. The standard medium is Provasoli-enriched natural seawater (PES), but Ectocarpus can also be grown in artificial seawater, which allows more precise control over the culture conditions. The algae can be cultivated either in plastic Petri dishes or in 10-L bottles with bubbling, if large amounts of biomass are required. Standard growth conditions are 13 degrees C with a 12h/12h d/night cycle and 20 umol photons m(-2) s(-1) irradiance using daylight-type fluorescent tubes. All manipulations of Ectocarpus cultures should be performed in a clean environment (if possible, under a laminar flow hood). Forceps should be dipped in ethanol and allowed to dry under the hood. PMID- 22301663 TI - Genetic crosses between Ectocarpus strains. AB - This article describes a procedure for conducting crosses between different strains of Ectocarpus. Crossing gametophytes to obtain the sporophyte generation is the most technically challenging stage of this process because diploid sporophytes have to be distinguished from the haploid partheno-sporophytes that result from the parthenogenetic germination of unfused gametes. This requires careful monitoring of the progeny of the genetic cross until they have developed sufficiently to be transferred to a separate Petri dish. Genetic crosses allow several classical genetic methodologies to be applied in Ectocarpus, including allelic complementation tests, backcrosses, combination of different genetic mutations, and outcrosses to create mapping populations. PMID- 22301665 TI - Supramolecular isomers of metal-organic frameworks: the role of a new mixed donor imidazolate-carboxylate tetradentate ligand. AB - Five new metal-organic frameworks prepared from the ligand 5-bis(3-(1 imidazolyl)propylcarbamoyl)terephthalate (bipta(2-)) and transition metal salts, Zn(2+) (1), Co(2+) (2), Mn(2+) (3, 4) and Cu(2+) (5), are reported. Single crystal X-ray studies reveal that the bipta(2-) ligand acts as a tetradentate ligand and combines with four-coordinate cationic metal nodes to give four connected framework structures. Whilst reaction of bipta(2-) with Zn(II) gives rise to a framework of diamondoid topology 1, the analogous frameworks with Co(II), Mn(II) and Cu(II) afford frameworks that incorporate square-planar nodes. Whereas 2 and 5 form frameworks of Cd(SO(4)) (cds) and square 4(4) nets (sql), respectively, reaction of Mn(II) with bipta(2-) forms two supramolecular isomers of topology cds for 3 and sql for 4. PMID- 22301666 TI - Lower plasma dehydroepiandrosterone concentration in the long term after severe accidental injury. PMID- 22301667 TI - Microglial activation in neuroinflammation: implications for the etiology of neurodegeneration. AB - BACKGROUND: Activated microglia secrete inflammatory cytokines and may play roles in the progression of neurodegenerative diseases. However, the mechanism underlying microglial activation remains unclear. OBJECTIVE: Our aim was to examine the regulation of activated microglia through their cell death and survival pathways. METHODS: We used mouse primary-cultured microglia, which are destined to die within a few days under ordinary culture conditions. The microglia live for longer than 1 month, without any measurable increase in apoptotic or necrotic cell death, when kept activated by sublethal concentrations of lipopolysaccharide (LPS). RESULTS: LPS-treated microglia showed changes in shape. LPS treatment had no effect on the level of the proapoptotic Bcl-2 associated X protein but increased the level of the antiapoptotic protein Bcl-xL at day 1. Furthermore, the level of microtubule-associated light chain 3-II, a marker protein for autophagy, was decreased 3 h after exposure to LPS. CONCLUSION: An increase in Bcl-xL seems to inhibit both apoptosis and autophagy. Our results suggest that long-lived microglia resulting from exposure to the optimal dose of LPS may play critical roles in the progression of neurodegeneration. PMID- 22301668 TI - Sepsis immunopathology: perspectives of monitoring and modulation of the immune disturbances. AB - Septic syndromes are the main cause of death in the intensive care units and although the mortality rates is slowly decreasing, the occurrence of the disease has been increasing. The pathogenesis of sepsis includes countless disturbances of the host immune system starting with a harmful, infection-triggered exaggerated inflammatory cascade, followed by the development of an immunoparalysis state. The latter contributes to the failure in pathogen eradication and leads to secondary infections, which are often the cause of fatal complications. In this review, we consider different novel therapeutic strategies for restoration of immune function. The use of glucocorticoids, intravenous immunoglobulins, heparin, recombinant human activated protein C, granulocyte macrophage colony-stimulating factor, granulocyte colony-stimulating factor, interferon-gamma, statins, macrolides and high-volume hemofiltration are discussed. Even though some clinical trials of these regimens are promising, the key to their successful application seems to be the precise monitoring of the status of immune system followed by implementation of the adequate therapy. Thus, in this paper we present disturbances in the immune system in the course of human sepsis, with special attention to the parameters that could be monitored and serve as markers for immunomodulatory therapies. We conclude by briefly presenting the current sepsis treatment strategy. PMID- 22301669 TI - Combinatorial cell-3D biomaterials cytocompatibility screening for tissue engineering using bioinspired superhydrophobic substrates. AB - We report on the development of a new array-based screening flat platform with the potential to be used as a high-throughput device based on biomimetic polymeric substrates for combinatorial cell/3D biomaterials screening assays in the context of tissue engineering. Polystyrene was used to produce superhydrophobic surfaces based on the so-called lotus effect. Arrays of hydrophilic regions could be patterned in such surfaces using UV/ozone radiation, generating devices onto which combinatorial hydrogel spots were deposited. The biological performance of encapsulated cells in hydrogels could be tested in an in vitro 3D environment assuming that each site was isolated from the others due to the high contrast of wettability between the patterned spots and the superhydrophobic surroundings. Three different polymers-chitosan, collagen and hyaluronic acid-were combined with alginate in different proportions in order to obtain combinatorial binary alginate-based polymeric arrays. The effect of the addition of gelatin to the binary structures was also tested. The gels were chemically analyzed by FTIR microscopic mapping. Cell culture results varied according to the hydrogel composition and encapsulated cell types (L929 fibroblast cells and MC3T3-E1 pre-osteoblast cells). Cell viability and number could be assessed by conventional methods, such as MTS reduction test and dsDNA quantification. Non-destructive image analysis was performed using cytoskeleton and nuclei staining agents and the results were consistent with the ones obtained by conventional sample-destructive techniques. Briefly, L929 cells showed higher number and viability for higher alginate-content and collagen-containing hydrogels, while MC3T3-E1 showed higher cell viability and cell number in lower alginate-content and chitosan containing hydrogels. The addition of gelatin did not influence significantly cell metabolic activity or cell number in any of the encapsulated cell types. PMID- 22301670 TI - Exhaled breath temperature increases after exercise in asthmatics and controls. AB - BACKGROUND: Exhaled breath temperature (EBT) has been suggested as a marker of airway inflammation in asthma. OBJECTIVES: The aim of the present study was to investigate EBT in asthmatic subjects compared to healthy controls after an exercise challenge test, and in subjects with exercise-induced bronchoconstriction compared to subjects without, and to compare with body temperatures. METHODS: A total of 21 healthy controls and 20 asthmatics were included. Forced expiratory volume in 1 s (FEV(1)), EBT and oral, axillary and auricular temperatures were measured before and after an exercise challenge test. RESULTS: FEV(1) % predicted (%p) was significantly lower in asthmatic subjects compared to healthy controls at all time points after exercise. The largest drop in FEV(1)%p correlated with EBT after 5 min. EBT increased markedly 5 min after exercise and remained high for at least 60 min. In asthmatics whose FEV(1) dropped by >10%, EBT was higher after 60 min compared to the remaining asthmatics. EBT correlated with oral temperature at all time points after exercise, with axillary temperature only at 15, 30 and 60 min, and not at all with auricular temperature. CONCLUSIONS: EBT is increased after exercise, and elevated EBT correlated with a drop in FEV(1)%p. The immediate increase in EBT did not differ between asthmatics and controls but remained elevated in the asthmatics whose FEV(1) dropped by >10%, indicating a different vascular response. PMID- 22301671 TI - Recombinant versus urinary gonadotrophin for ovarian stimulation in assisted reproductive technology cycles. A Cochrane review. PMID- 22301672 TI - Reinvestigation of a former concerted proton-electron transfer (CPET), the reduction of a hydrogen-bonded complex between a proton donor and the anion radical of 3,5-di-tert-butyl-1,2-benzoquinone. AB - In 2001, Lehmann and Evans (J. Phys. Chem. B, 2001, 105, 8877-8884) reported that the electrochemical reduction of a hydrogen-bonded complex between a proton donor and the anion radical of 3,5-di-tert-butyl-1,2-benzoquinone in acetonitrile proceeded by a concerted proton-electron transfer (CPET) reaction in which electron transfer from the electrode and proton transfer from proton donor to the quinone moiety occurred concertedly. Support for this conclusion was based upon ruling out both of the competing two-step processes, electron transfer followed by proton transfer (EP) and proton transfer followed by electron transfer (PE). In the course of studies of related compounds it was decided to reinvestigate the reduction of 3,5-di-tert-butyl-1,2-benzoquinone. It was discovered that the earlier conclusion that a CPET reaction was occurring was tenable only for the particular electrolyte that was used, tetrabutylammonium hexafluorophosphate and for lower concentrations of the quinone. Even the small change of carrying out the reduction of the quinone in the presence of water with tetramethylammonium hexafluorophosphate as electrolyte, produced voltammograms with clear signatures that the process was EP rather than CPET. Even more dramatic effects were seen with cesium, potassium or sodium ions in the electrolyte. A general reaction scheme to explain results with all electrolytes will be presented. PMID- 22301673 TI - 'Probabilistic' approach to Richardson equations. AB - It is known that solutions of Richardson equations can be represented as stationary points of the 'energy' of classical free charges on the plane. We suggest considering the 'probabilities' of the system of charges occupying certain states in the configurational space at the effective temperature given by the interaction constant, which goes to zero in the thermodynamical limit. It is quite remarkable that the expression of 'probability' has similarities with the square of the Laughlin wavefunction. Next, we introduce the 'partition function', from which the ground state energy of the initial quantum-mechanical system can be determined. The 'partition function' is given by a multidimensional integral, which is similar to the Selberg integrals appearing in conformal field theory and random-matrix models. As a first application of this approach, we consider a system with the constant density of energy states at arbitrary filling of the energy interval where potential acts. In this case, the 'partition function' is rather easily evaluated using properties of the Vandermonde matrix. Our approach thus yields a quite simple and short way to find the ground state energy, which is shown to be described by a single expression all over from the dilute to the dense regime of pairs. It also provides additional insight into the physics of Cooper-paired states. PMID- 22301674 TI - Carbon nanotube-loaded electrospun LiFePO4/carbon composite nanofibers as stable and binder-free cathodes for rechargeable lithium-ion batteries. AB - LiFePO(4)/CNT/C composite nanofibers were synthesized by using a combination of electrospinning and sol-gel techniques. Polyacrylonitrile (PAN) was used as the electrospinning media and carbon source. Functionalized CNTs were used to increase the conductivity of the composite. LiFePO(4) precursor materials, PAN and functionalized CNTs were dissolved or dispersed in N,N-dimethylformamide separately and they were mixed before electrospinning. LiFePO(4) precursor/CNT/PAN composite nanofibers were then heat-treated to obtain LiFePO(4)/CNT/C composite nanofibers. Fourier transform infrared spectroscopy measurements were done to demonstrate the functionalization of CNTs. The structure of LiFePO(4)/CNT/C composite nanofibers was determined by X-ray diffraction analysis. The surface morphology and microstructure of LiFePO(4)/CNT/C composite nanofibers were characterized using scanning electron microscopy and transmission electron microscopy. Electrochemical performance of LiFePO(4)/CNT/C composite nanofibers was evaluated in coin-type cells. Functionalized CNTs were found to be well-dispersed in the carbonaceous matrix and increased the electrochemical performance of the composite nanofibers. As a result, cells using LiFePO(4)/CNT/C composite nanofibers have good performance, in terms of large capacity, extended cycle life, and good rate capability. PMID- 22301675 TI - Ponatinib is active against imatinib-resistant mutants of FIP1L1-PDGFRA and KIT, and against FGFR1-derived fusion kinases. PMID- 22301676 TI - Spleen tyrosine kinase (Syk) is a potent target for GvHD prevention at different cellular levels. AB - Acute graft-versus-host disease (GvHD) limits the applicability of allogeneic hematopoietic cell transplantation for the treatment of leukemia. GvHD occurs as a consequence of multiple activating events in antigen-presenting cells (APCs) and T cells (Tcs). Spleen tyrosine kinase (Syk) is an intracellular non-receptor tyrosine kinase involved in multiple signaling events of immune cells. Therefore, we hypothesized that Syk may be a promising target to inhibit GvHD, which involves activation of different immune cell populations. In vivo expansion of luciferase(+) donor Tcs in mice developing GvHD was reduced by treatment with the Syk inhibitor Fostamatinib, which led to increased survival and reduced histologically confirmed GvHD severity. Importantly, in vivo and in vitro cytotoxicity against leukemia target cells and anti-murine cytomegalovirus immune responses were not impacted by Fostamatinib. In APCs Syk inhibition reduced the expression of costimulatory molecules and disrupted cytoskeletal organization with consecutive APC migratory defects in vitro and in vivo while phagocytic activity remained intact. On the basis of these immunomodulatory effects on different cell populations, we conclude that Syk targeting in alloantigen activated Tcs and APCs with pharmacologic inhibitors, already applied successfully in anti-lymphoma therapy, has clinical potential to reduce GvHD, especially as anti-leukemia and anti-viral immunity were preserved. PMID- 22301677 TI - Carbazole dendronised triphenylamines as solution processed high Tg amorphous hole-transporting materials for organic electroluminescent devices. AB - Carbazole dendrimers up to 4th generation were synthesized. They showed significantly high T(g), amorphous and stable electrochemical properties, and great potential as solution processed hole-transporting materials for OLEDs. Alq3 based green devices exhibited high luminance efficiency and CIE coordinates of 4.45 cd A(-1) and (0.29, 0.53), respectively. PMID- 22301678 TI - Synthesis and characterization of cobalt(II) complexes with tripodal polypyridine ligand bearing pivalamide groups. Selective formation of six- and seven coordinate cobalt(II) complexes. AB - The reactions of CoX(2) (X = Cl(-), Br(-), I(-) and ClO(4)(-)) with the tripodal polypyridine N(4)O(2)-type ligand bearing pivalamide groups, bis(6-(pivalamide-2 pyridyl)methyl)(2-pyridylmethyl)amine ligand (H(2)BPPA), afforded two types of Co(II) complexes as follows. One type is purple-coloured Co(II) complexes, [CoCl(2)(H(2)BPPA)] (1(Cl)) and [CoBr(2)(H(2)BPPA)] (1(Br)) which were prepared when X = Cl(-) and Br(-), respectively. The other type is pale pink-coloured Co(II) complexes, [Co(MeOH)(H(2)BPPA)](ClO(4)(-))(2) (2.(ClO(4)(-))(2)) and [Co(MeCN)(H(2)BPPA)](I(-))(2) (2.(I(-))(2)), which were obtained when X = I(-) and ClO(4)(-), respectively. From the reaction of 1(Cl) and NaN(3), a purple coloured complex, [Co(N(3))(2)(H(2)BPPA)] (1(azide)), was obtained. These Co(II) complexes were characterized by X-ray structural analysis, IR and reflectance spectroscopies, and magnetic susceptibility measurements. All these Co(II) complexes were shown to be in a d(7) high-spin state based on magnetic susceptibility measurements. The former Co(II) complexes revealed a six coordinate octahedron with one amine nitrogen, three pyridyl nitrogens, and two counter anions, and one coordinated anion, Cl(-), Br(-) and N(3)(-), forming intramolecular hydrogen bonds with two pivalamide N-H groups. On the other hand, the latter Co(II) complexes showed a seven-coordinate face-capped octahedron with one amine nitrogen, three pyridyl nitrogens, two pivalamide carbonyl oxygens and MeCN or MeOH. In these structures, intramolecular hydrogen bonding interaction was not observed, and the metal ion was coordinated by the pivalamide carbonyl oxygens and solvent molecule instead of the counter anions. The difference in coordination geometries might be attributable to the coordination ability and ionic radii of the counteranions; smaller strongly binding anions such as Cl(-), Br(-) and N(3)(-) gave the former complexes, whereas bulky weakly binding anions such as I(-) and ClO(4)(-) afforded the latter ones. In order to demonstrate this hypothesis, the small stronger coordinating ligand, azide, was added to complexes 2.(ClO(4)(-))(2) to obtain the dinuclear cobalt(II) complex in which two six coordinate octahedral cobalt(II) species were bridged with azide, 3.(ClO(4)(-)). Also, the abstraction reaction of halogen anions from complexes 1(Cl) by AgSbF(6) gave a pale pink Co(II) complex assignable to 2.(SbF(6)(-))(2). PMID- 22301679 TI - A randomized controlled trial of a cognitive rehabilitation intervention for persons with multiple sclerosis. AB - OBJECTIVE: To explore the feasibility and effects of a computer-assisted cognitive rehabilitation intervention - Memory, Attention, and Problem Solving Skills for Persons with Multiple Sclerosis (MAPSS-MS) - for persons with multiple sclerosis on cognitive performance, memory strategy use, self-efficacy for control of symptoms and neuropsychological competence in activities of daily living (ADL). DESIGN: A randomized controlled single-blinded trial with treatment and wait list control groups. SETTING: Southwestern United States. SUBJECTS: Convenience sample of 61 persons (34 treatment, 27 wait list control) with multiple sclerosis (mean age 47.9 years, SD 8.8). INTERVENTION: The eight-week MAPSS-MS intervention program included two components: (a) eight weekly group sessions focused on building efficacy for use of cognitive compensatory strategies and (b) a computer-assisted cognitive rehabilitation program with home based training. OUTCOME MEASURES: A neuropsychological battery of performance tests comprising the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) and self-report instruments (use of memory strategies, self efficacy for control of multiple sclerosis and neuropsychological competence in ADL) were completed at baseline, two months (after classes), and at five months. RESULTS: Both groups improved significantly (P < 0.05) over time on most measures in the MACFIMS battery as well as the measures of strategy use and neuropsychological competence in ADL. There was a significant group-by-time interaction for scores on the measures of verbal memory and the use of compensatory strategies. CONCLUSIONS: The MAPSS-MS intervention was feasible and well-accepted by participants. Given the large relative increase in use of compensatory strategies by the intervention group, it holds promise for enhancing cognitive function in persons with multiple sclerosis. PMID- 22301680 TI - Predictors of patient adherence to cognitive-behavioral therapy for obsessive compulsive disorder. PMID- 22301681 TI - Dysregulation of Ca2+ homeostasis in Alzheimer's disease: role in acetylcholinesterase production and AMPA receptor internalization. AB - Amyloid-beta (Abeta)-induced Ca(2+) influx into neurons has been well described since it was first reported almost 20 years ago. Ca(2+) influx can disrupt mechanisms of long-term potentiation and long-term depression and increase neuronal susceptibility to excitotoxicity. Our studies show that Abeta also causes an increase in acetylcholinesterase (AChE) levels and induces AMPA receptor internalization through Ca(2+)-dependent mechanisms. As Abeta-induced Ca(2+) entry may increase neuronal excitability, the increase in AChE and the downregulation of cell surface AMPA receptors may be part of a homeostatic mechanism which maintains normal levels of cholinergic and glutamatergic signaling. PMID- 22301682 TI - Interaction between VEGF receptor-2 gene polymorphisms and dietary patterns on blood glucose and lipid levels in Chinese Malaysian adults. AB - BACKGROUND/AIMS: The prevalence of lifestyle-related chronic diseases is increasing and gene-diet interaction studies are limited among the Malaysian population. This study was conducted to evaluate the association and interaction effects of vascular endothelial growth factor receptor-2(VEGFR2) gene polymorphisms and dietary patterns on anthropometric and biochemical risk factors of chronic diseases in 179 Chinese Malaysian adults. METHODS: Genotyping of rs1870377 and rs2071559 was performed by real-time PCR using TaqMan probes. Dietary patterns were constructed from the food frequency questionnaire using factor analysis. Anthropometric measurements: body mass index (BMI), systolic and diastolic blood pressure and biomarkers: blood glucose, glycated hemoglobin A1c (HbA1c) and lipids were obtained. RESULTS: Two dietary patterns: 'Balanced diet' and 'Meat, rice and noodles diet' (MRND) were extracted. MRND was associated with higher BMI, blood pressure, blood glucose and lipids, while T alleles in both rs1870377 and rs2071559 were associated with higher blood lipids (p < 0.05). The interaction of MRND and rs1870377 had a borderline effect on blood HbA1c after adjusting for confounders (p = 0.057). CONCLUSIONS: A dietary pattern of MRND and VEGFR2 gene polymorphisms were both associated with increased health risks of lifestyle-related chronic diseases particularly blood glucose and lipid levels in Chinese Malaysian adults. PMID- 22301683 TI - Methicillin resistance reduces the virulence of healthcare-associated methicillin resistant Staphylococcus aureus by interfering with the agr quorum sensing system. AB - The difficulty in successfully treating infections caused by methicillin resistant Staphylococcus aureus (MRSA) has led to them being referred to as highly virulent or pathogenic. In our study of one of the major healthcare associated MRSA (HA-MRSA) clones, we show that expression of the gene responsible for conferring methicillin resistance (mecA) is also directly responsible for reducing the ability of HA-MRSA to secrete cytolytic toxins. We show that resistance to methicillin induces changes in the cell wall, which affects the bacteria's agr quorum sensing system. This leads to reduced toxin expression and, as a consequence, reduced virulence in a murine model of sepsis. This diminished capacity to cause infection may explain the inability of HA-MRSA to move into the community and help us understand the recent emergence of community-associated MRSA (CA-MRSA). CA-MRSA typically express less penicillin-binding protein 2a (encoded by mecA), allowing them to maintain full virulence and succeed in the community environment. PMID- 22301684 TI - Miniaturised technologies for the development of artificial lipid bilayer systems. AB - Artificially reproducing cellular environments is a key aim of synthetic biology, which has the potential to greatly enhance our understanding of cellular mechanisms. Microfluidic and lab-on-a-chip (LOC) techniques, which enable the controlled handling of sub-microlitre volumes of fluids in an automated and high throughput manner, can play a major role in achieving this by offering alternative and powerful methodologies in an on-chip format. Such techniques have been successfully employed over the last twenty years to provide innovative solutions for chemical analysis and cell-, molecular- and synthetic- biology. In the context of the latter, the formation of artificial cell membranes (or artificial lipid bilayers) that incorporate membrane proteins within miniaturised LOC architectures offers huge potential for the development of highly sensitive molecular sensors and drug screening applications. The aim of this review is to give a comprehensive and critical overview of the field of microsystems for creating and exploiting artificial lipid bilayers. Advantages and limitations of three of the most popular approaches, namely suspended, supported and droplet based lipid bilayers, are discussed. Examples are reported that show how artificial cell membrane microsystems, by combining together biological procedures and engineering techniques, can provide novel methodologies for basic biological and biophysical research and for the development of biotechnology tools. PMID- 22301685 TI - A metallic surface state with uniaxial spin polarization on Tl/Ge(111)-(1 * 1). AB - We show that a metallic surface state is formed on Tl/Ge(111)-(1 * 1). The surface state forms electron pockets around K of the surface Brillouin zone. A first-principles calculation reveals that the electron pockets are composed of a single branch of a spin-split surface-state band. The spin quantization axis is along the surface normal and inverts according to the time-reversal symmetry. Since this spin-split branch is the unique metallic band on this surface, the surface conductivity should be governed by this spin-split branch, suggesting a possible spin-polarized electric current. PMID- 22301686 TI - Gene-selective histone H3 acetylation in the absence of increase in global histone acetylation in liver of rats chronically fed alcohol. AB - AIMS: The aim of this study was to determine the effect of chronic ethanol feeding on acetylation of histone H3 at lysine 9 (H3-Lys9) at promoter and coding regions of genes for class I alcohol dehydrogenase (ADH I), inducible nitric oxide synthase (iNOS), Bax, p21, c-met and hepatocyte growth factor in the rat liver. METHODS: Rats were fed ethanol-containing liquid diet (5%, w/v) for 1-4 weeks. The global level of acetylation of H3-Lys9 in the liver was examined by western blot analysis. The levels of mRNA for various genes were measured by real time reverse transcriptase-polymerase chain reaction. The association of acetylated histone H3-Lys9 with the different regions of genes was monitored by chromatin immunoprecipitation assay. RESULTS: Chronic ethanol treatment increased mRNA expression of genes for iNOS, c-jun and ADH 1. Chronic ethanol treatment did not cause increase in global acetylation of H3-Lys9, but significantly increased the association of acetylated histone H3-Lys9 in the ADH I gene, both in promoter and in coding regions. In contrast, chronic ethanol treatment did not significantly increase the association of acetylated histone H3-Lys9 with iNOS and c-jun genes. CONCLUSION: Chronic ethanol exposure increased the gene selective association of acetylated H3-Lys9 in the absence of global histone acetylation. Thus, not all genes expressed by ethanol are linked to transcription via histone H3 acetylation at Lys9. PMID- 22301687 TI - Impact of different reference period definitions in the quantification of alcohol consumption: results from a nationwide STEPS survey in Mozambique. AB - AIMS: To compare the estimates of alcohol consumption in Mozambique obtained with different reference period definitions. This is a critical methodological aspect when measuring alcohol consumption and its impact is likely to vary across settings. METHODS: A nationally representative sample of 3264 Mozambicans aged 25 64 years was evaluated in a community-based cross-sectional study conducted between September and November 2005. Face-to-face interviews were conducted following the World Health Organization-Stepwise approach to Surveillance methodology. The amount of alcohol consumed was estimated among current drinkers, using the previous week (1W) and the 12 months (12M) prior to the data collection as the reference. RESULTS: Among drinkers, the prevalence of consumption of >14 drinks/week was higher in men (12M: 18.6 vs. 7.8%; 1W: 16.3 vs. 6.1%), although the prevalence of excessive weekly intake (>7 drinks for women and >14 drinks for men) was higher among women (12M: 25.9 vs. 18.6%; 1W: 18.1 vs. 16.3%). The concordance between the reported intakes according to the reference period was low (kappa = 0.25). CONCLUSION: In this setting where alcohol consumption is a male-dominated behaviour, among drinkers the prevalence of gender-defined excessive amounts was higher in women. The concordance between different recall periods was low and this needs to be taken into account when comparing results from different studies. PMID- 22301688 TI - Sleep in the rock hyrax, Procavia capensis. AB - We investigated sleep in therock hyrax, Procavia capensis, a social mammal that typically lives in colonies on rocky outcrops throughout most parts of Southern Africa. The sleep of 5 wild-captured, adult rock hyraxes was recorded continuously for 72 h using telemetric relay of signals and allowing unimpeded movement. In addition to waking, slow wave sleep (SWS) and an unambiguous rapid eye movement (REM) state, a sleep state termed somnus innominatus (SI), characterized by low-voltage, high-frequency electroencephalogram, an electromyogram that stayed at the same amplitude as the preceding SWS episode and a mostly regular heart rate, were identified. If SI can be considered a form of low-voltage non-REM, the implication would be that the rock hyrax exhibits the lowest amount of REM recorded for any terrestrial mammal studied to date. Conversely, if SI is a form of REM sleep, it would lead to the classification of a novel subdivision of this state; however, further investigation would be required. The hyraxes spent on average 15.89 h (66.2%) of the time awake, 6.02 h (25.1%) in SWS, 43 min (3%) in SI and 6 min (0.4%) in REM. The unambiguous REM sleep amounts were on average less than 6 min/day. The most common state transition pathway in these animals was found to be wake -> SWS -> wake. No significant differences were noted with regard to total sleep time, number of episodes and episode duration for all states between the light and dark periods.Thus, prior classification of the rock hyrax as strongly diurnal does not appear to hold under controlled laboratory conditions. PMID- 22301689 TI - Bim regulates B-cell receptor-mediated apoptosis in the presence of CD40 signaling in CD40-pre-activated splenic B cells differentiating into plasma cells. AB - B-cell receptor (BCR)-mediated apoptosis is critical for B-cell development and homeostasis. CD40 signaling has been shown to protect immature or mature B cells from BCR-mediated apoptosis. In this study, to understand the fate of CD40-pre activated splenic B cells stimulated by BCR engagement in the presence of CD40 signaling, murine splenic B cells were cultured with anti-Igkappa and anti-CD40 antibodies after pre-activation with anti-CD40 antibody. We found that apoptosis was induced in the cultured B cells even in the presence of CD40 signaling during the 3-4 days cultivation. We detected up-regulation of Bim expression followed by Bax activation in this apoptotic process and cessation of the apoptosis in Bim deficient B cells, indicating that Bim is a key regulator of the BCR-mediated apoptosis in the presence of CD40 signaling in CD40-pre-activated B cells. Importantly, this BCR-mediated apoptosis in CD40-pre-activated B cells was shown to be induced at the initiation of plasma cell differentiation at around the preplasmablast stage, and Bim-deficient B cells cultured under these conditions differentiated into plasma cells. Additionally, transforming growth factor-beta was found to protect CD40-pre-activated B cells from BCR-mediated apoptosis in the presence of CD40 signaling. Our identified BCR-mediated apoptosis, which is unpreventable by CD40 signaling, suggests a potential mechanism that regulates the elimination of peripheral B cells, which should be derived from nonspecific T dependent activation of bystander B cells and continuous stimulation with antigens including self-antigens in the presence of T cell help through CD40. PMID- 22301690 TI - Stabilisation of water-soluble platinum nanoparticles by phosphonic acid derivatives. AB - Sodium 2-(diphenylphosphino)ethyl phosphonate (1) was investigated as a stabilising agent for platinum nanoparticles (Pt-NPs) in aqueous solution. This phosphino phosphonate is known to stabilise rhodium nanoparticles (NPs) in water. Here we report that in the case of Pt-NPs this ligand is indirectly involved in the stabilisation mechanism and the actual stabilisation agent is the platinum complex Na(2)[Pt(1)(2)] (2). The reduction of platinum(II) salts in the presence of the phosphonates 1, 2, sodium 2-(diphenylphosphoryl)ethyl phosphonate (3) and 3,3,3-triphenylpropyl phosphonate (4) leads to stable platinum NPs with a remarkably narrow particle size distribution. These platinum NPs show high catalytic activity in the hydrogenation of 1-hexene and 1-chloro-3-nitrobenzene under biphasic as well as heterogeneous (supported on charcoal) conditions. The activity of the supported NPs was 30 times higher than the commercially available catalyst Pt(0) EnCat(r). Furthermore, the single-crystal X-ray structures of (1)(MeOH)(2)(H(2)O)(2), (3)(H(2)O)(4), and (4)(2)(H(2)O)(17) have been determined. PMID- 22301691 TI - beta-Galactomannan and Saccharomyces cerevisiae var. boulardii modulate the immune response against Salmonella enterica serovar Typhimurium in porcine intestinal epithelial and dendritic cells. AB - Salmonella enterica serovar Typhimurium is a facultative intracellular pathogen that causes inflammation, necrosis, and diarrhea in pigs, as well as being an important source of food-borne diseases in humans. Probiotics and prebiotics are promising alternatives to antibiotics to control and prevent intestinal infections. The present work investigated a recently developed beta-galactomannan (betaGM) prebiotic compared to the proven probiotic Saccharomyces cerevisiae var. boulardii on porcine ileum intestinal epithelial cells (IECs) of the IPI-2I line and monocyte-derived dendritic cells (DCs) cocultured in vitro with Salmonella. We observed that both S. cerevisiae var. boulardii and betaGM inhibited the association of Salmonella with IECs in vitro. Our data indicated that betaGM has a higher ability than S. cerevisiae var. boulardii to inhibit Salmonella-induced proinflammatory mRNA (cytokines tumor necrosis factor alpha [TNF-alpha], interleukin-1alpha [IL-1alpha], IL-6, and granulocyte-macrophage colony stimulating factor [GM-CSF] and chemokines CCL2, CCL20, and CXCL8) and at protein levels (IL-6 and CXCL8). Additionally, betaGM and S. cerevisiae var. boulardii induced some effects on DCs that were not observed on IECs: betaGM and S. cerevisiae var. boulardii showed slight upregulation of mRNA for TNF-alpha, GM CSF, and CCR7 receptor on porcine monocyte-derived dendritic cells (DCs). Indeed, the addition of betaGM or S. cerevisiae var. boulardii on DCs cocultured with Salmonella showed higher gene expression (mRNA) for TNF-alpha, GM-CSF, and CXCL8 compared to that of the control with Salmonella. In conclusion, the addition of betaGM inhibits Salmonella-induced proinflammatory profiles in IECs but may promote DC activation, although associated molecular mechanisms remain to be elucidated. PMID- 22301692 TI - Antituberculosis IgG antibodies as a marker of active Mycobacterium tuberculosis disease. AB - Anti-Mycobacterium tuberculosis IgG antibodies may aid in the diagnosis of active M. tuberculosis disease. We studied whether anti-M. tuberculosis IgG antibodies are elevated in active M. tuberculosis disease and assessed factors contributing to false-positive and -negative results. A retrospective study of 2,150 individuals tested by the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay was conducted at the University of Utah, ARUP Laboratories, November 2008 to December 2010. All samples were tested with the InBios Active TbDetect antituberculosis (anti-TB) IgG antibody assay. Of 1,044 patients with a positive QFT-GIT, 59 (5.7%) were positive for M. tuberculosis antibodies. Fourteen of 1,106 (1.3%) with a negative or indeterminate QFT-GIT were positive for M. tuberculosis antibodies. M. tuberculosis antibody tests were positive in 61.5% with confirmed active M. tuberculosis disease and other mycobacterial infections. Over half of the false-negative M. tuberculosis antibody tests occurred in patients >= 90 years of age. False positives were seen in 12.9% of autoimmune patients. The odds ratio of being positive by the QFT-GIT and the InBios TB IgG assay increased with confirmed M. tuberculosis disease or highly suspected M. tuberculosis disease and was 86.7 (95% confidence interval [CI], 34.4 to 218.5) in these two groups compared to patients negative by both tests. Although anti-M. tuberculosis antibodies can be detected in patients with active M. tuberculosis disease, caution should be used with patients where immunoglobulin levels may be decreased or patients with autoantibodies. PMID- 22301693 TI - Antigen targeting to major histocompatibility complex class II with streptococcal mitogenic exotoxin Z-2 M1, a superantigen-based vaccine carrier. AB - Streptococcal mitogenic exotoxin Z-2 (SMEZ-2) is a streptococcal superantigen that primarily stimulates human T cells bearing Vbeta8 and mouse T cells bearing Vbeta11. Mutagenesis of T cell receptor (TCR)-binding residues (W75L, K182Q, D42C) produced a mutant called M1 that was >10(5)-fold less active toward human peripheral blood lymphocytes and splenocytes from transgenic mice that express human CD4 and either human HLA-DR3-DQ2 or HLA-DR4-DQ8. Similarly, cytokine production in response to M1 in lymphocyte culture was rendered undetectable, and no change in the frequency of Vbeta11-bearing T cells in mice receiving M1 was observed. M1 toxoid was tested as a potential vaccine conjugate. Vaccination with 1 to 10 MUg M1 conjugated to ovalbumin (M1-ovalbumin) resulted in more rapid and quantitatively higher levels of anti-ovalbumin IgG, with endpoint titers being 1,000- to 10,000-fold greater than those in animals immunized with unconjugated ovalbumin. Substantially higher levels of anti-ovalbumin IgG were observed in mice transgenic for human major histocompatibility complex (MHC) class II. Substitution of M1 with an MHC class II binding mutant (DM) eliminated enhanced immunity, suggesting that M1 enhanced the delivery of antigen via MHC class II positive antigen-presenting cells that predominate within lymphoid tissue. Immunization of animals with a conjugate consisting of M1 and ovalbumin peptide from positions 323 to 339 generated levels of anti-peptide IgG 100-fold higher than those in animals immunized with peptide alone. Coupling of a TCR-defective superantigen toxoid presents a new strategy for conjugate vaccines with the additional benefit of targeted delivery to MHC class II-bearing cells. PMID- 22301694 TI - The presence of alpha interferon at the time of infection alters the innate and adaptive immune responses to porcine reproductive and respiratory syndrome virus. AB - Porcine reproductive and respiratory syndrome (PRRS) is one of the most devastating and costly diseases to the swine industry worldwide. Overall, the adaptive immune response to PRRS virus (PRRSV) is weak, which results in delayed elimination of virus from the host and inferior vaccine protection. PRRSV has been shown to induce a meager alpha interferon (IFN-alpha) response, and we hypothesized that elevated IFN-alpha levels early in infection would shorten the induction time and increase elements of the adaptive immune response. To test this, we measured both antibody and cell-mediated immunity in pigs after the administration of a nonreplicating human adenovirus type 5 vector expressing porcine IFN-alpha (Ad5-pIFN-alpha) at the time of PRRSV infection and compared the results to those for pigs infected with PRRSV alone. Viremia was delayed, and there was a decrease in viral load in the sera of pigs administered the Ad5-pIFN alpha. Although seroconversion was slightly delayed in pigs receiving Ad5-pIFN alpha, probably due to the early reduction in viral replication, little difference in the overall or neutralizing antibody response was seen. However, there was an increase in the number of virus-specific IFN-gamma-secreting cells detected in the pigs receiving Ad5-pIFN-alpha, as well as an altered cytokine profile in the lung at 14 days postinfection, indicating that the presence of IFN alpha at the time of infection can alter innate and adaptive immune responses to PRRSV. PMID- 22301695 TI - Serological diagnosis of paracoccidioidomycosis through a Western blot technique. AB - Paracoccidioidomycosis (PCM) is a serious infectious disease that progresses toward death if untreated. Its confirmatory diagnosis is made by the detection of the fungus Paracoccidioides brasiliensis in a direct mycological examination or by histopathology. However, these techniques are of low sensitivity. Serological tests seem to be more promising. The objective of this study was to test Western blot (WB) analysis using sera from patients suspected of PCM to determine whether it represents a safe and sensitive serological technique for a rapid and effective diagnosis for this disease. Sera from 517 patients were analyzed through WB analysis and double-immunodiffusion (DID) techniques using a crude exoantigen of P. brasiliensis 339. DID gave positive reactions for 140 sera (27%) and WB for 250 sera (48.4%). All sera that had a positive reaction by DID also had a positive result with a 43-kDa glycoprotein by WB analysis. Among the 377 samples that were negative by DID, 29.1% were reactive in WB analysis. For the cutoff dilution used (1:400), a positive reaction was not observed with any of the 102 sera from patients with other diseases in regions where such diseases are endemic and 30 healthy individuals tested as negative controls. These results prove WB analysis to be a sensitive technique and suggest its inclusion among routine laboratory assays as a safe method for PCM diagnosis. PMID- 22301696 TI - Improved skin test for differential diagnosis of bovine tuberculosis by the addition of Rv3020c-derived peptides. AB - A peptide cocktail derived from the mycobacterial antigens ESAT-6, CFP-10, and Rv3615c allowed differentiation between Mycobacterium bovis-infected and M. bovis bacillus Calmette-Guerin (BCG)-vaccinated cattle when used as a skin test reagent for a "DIVA" test (i.e., a test capable of differentiating infected and uninfected vaccinated animals). Addition of the antigen Rv3020c improves the diagnostic sensitivity without compromising specificity in the face of BCG or Johne's disease vaccination. PMID- 22301697 TI - Delivery of a DNA vaccine for Alzheimer's disease by electroporation versus gene gun generates potent and similar immune responses. AB - BACKGROUND: Induction of a humoral response against amyloid-beta peptide may be beneficial for Alzheimer's disease (AD) patients and may alleviate the onset and progression of AD. DNA-based vaccination provides a unique alternative method of immunization for treatment and prevention of AD. Currently, the two major delivery methods used for enhancing DNA uptake and immune responses to DNA vaccines in humans are electroporation (EP) and gene gun (GG). OBJECTIVE: The goal of this translational study was to evaluate the efficacy of an AD DNA epitope vaccine (DepVac) delivered intramuscularly by EP or intradermally by GG. METHODS: Humoral and cellular immune responses to immunization with DepVac were evaluated by ELISA and ELISPOT, respectively. Functional activity of the antibodies was also assessed. RESULTS: EP- and GG-mediated immunizations with DepVac induced similar anti-amyloid-beta (Abeta) antibody and T cell responses. Anti-Abeta antibodies bound to amyloid plaques in AD brain tissue and to toxic forms of Abeta(42) peptide. CONCLUSION: Both delivery methods are effective at promoting potent antibodies specific for Abeta. PMID- 22301698 TI - Coping styles in chronic fatigue syndrome: findings from a population-based study. PMID- 22301699 TI - Genomic analysis of marginal zone and lymphoplasmacytic lymphomas identified common and disease-specific abnormalities. AB - Lymphoplasmacytic lymphomas and marginal zone lymphomas of nodal, extra-nodal and splenic types account for 10% of non-Hodgkin lymphomas. They are similar at the cell differentiation level, sometimes making difficult to distinguish them from other indolent non-Hodgkin lymphomas. To better characterize their genetic basis, we performed array-based comparative genomic hybridization in 101 marginal zone lymphomas (46 MALT, 35 splenic and 20 nodal marginal zone lymphomas) and 13 lymphoplasmacytic lymphomas. Overall, 90% exhibited copy-number abnormalities. Lymphoplasmacytic lymphomas demonstrated the most complex karyotype (median=7 copy-number abnormalities), followed by MALT (4), nodal (3.5) and splenic marginal zone lymphomas (3). A comparative analysis exposed a group of copy number abnormalities shared by several or all the entities with few disease specific abnormalities. Gain of chromosomes 3, 12 and 18 and loss of 6q23-q24 (TNFAIP3) were identified in all entities. Losses of 13q14.3 (MIRN15A-MIRN16-1) and 17p13.3-p12 (TP53) were found in lymphoplasmacytic and splenic marginal zone lymphomas; loss of 11q21-q22 (ATM) was found in nodal, splenic marginal zone and lymphoplasmacytic lymphomas and loss of 7q32.1-q33 was found in MALT, splenic and lymphoplasmacytic lymphomas. Abnormalities affecting the nuclear factor kappa B pathway were observed in 70% of MALT and lymphoplasmacytic lymphomas and 30% of splenic and nodal marginal zone lymphomas, suggesting distinct roles of this pathway in the pathogenesis/progression of these subtypes. Elucidation of the genetic alterations contributing to the pathogenesis of these lymphomas may guide to design-specific therapeutic approaches. PMID- 22301700 TI - Cholangiocyte cilia are abnormal in syndromic and non-syndromic biliary atresia. AB - Biliary atresia (BA) is a neonatal disorder characterized by aggressive fibroinflammatory obliteration of the biliary tract. Approximately 20 percent of BA patients demonstrate left-right laterality defects (syndromic BA). Cilia participate in important physiological functions in cholangiocytes, and as some ciliopathies have been associated with both laterality defects and hepatic fibrosis, we hypothesized that patients with syndromic BA exhibit abnormalities of cholangiocyte cilia that disrupt cholangiocyte homeostasis. Nine BA specimens were studied, including pre-Kasai diagnostic biopsies (n=7) and liver explants (n=2). Five specimens were from patients with laterality defects. These were compared with normal pediatric livers, as well as livers affected by primary sclerosing cholangitis, Wilson's disease, and cardiac cirrhosis. Biopsy sections were stained with antibodies against keratin 19 (a cholangiocyte marker) and acetylated alpha-tubulin (a cilia marker) and were visualized by confocal microscopy. Computer-assisted relative quantification was used to compare staining of cilia within bile ducts among samples. Surprisingly, cilia in BA specimens were significantly shorter, abnormal in their orientation, and less abundant compared with normal liver and disease controls regardless of the presence of a laterality defect. There are significant abnormalities of cholangiocyte cilia in both syndromic and non-syndromic BA livers compared with normal livers and livers affected by other cholestatic diseases. Although this may result from severe cholestasis or inflammation, it may also reflect common mechanistic pathways in different forms of BA and may have important implications for understanding the progression of the disease. PMID- 22301701 TI - Loss of keratin 13 in oral carcinoma in situ: a comparative study of protein and gene expression levels using paraffin sections. AB - Immunohistochemical loss of keratin (K)13 is one of the most valuable diagnostic criteria for discriminating carcinoma in situ (CIS) from non-malignancies in the oral mucosa while K13 is stably immunolocalized in the prickle cells of normal oral epithelium. To elucidate the molecular mechanism for the loss of K13, we compared the immunohistochemical profiles for K13 and K16 which is not expressed in normal epithelia, but instead enhanced in CIS, with their mRNA levels by in situ hybridization in formalin-fixed paraffin sections prepared from 23 CIS cases of the tongue, which were surgically removed. Reverse transcriptase-PCR was also performed using RNA samples extracted from laser-microdissected epithelial fragments of the serial paraffin sections in seven of the cases. Although more enhanced expression levels for K16 were confirmed at both the protein and gene levels in CIS in these seven cases, the loss of K13 was associated with repressed mRNA levels in four cases, but not in the other three cases. The results suggest that the loss of K13 is partly due to its gene repression, but may also be due to some unknown post-translational events. PMID- 22301702 TI - Clinical assessment of PTEN loss in endometrial carcinoma: immunohistochemistry outperforms gene sequencing. AB - PTEN (phosphatase and tensin homolog) is a tumor suppressor that negatively regulates the PI3K-AKT signaling pathway, which is implicated in the pathogenesis of endometrial carcinoma. Sanger sequencing has been considered to be the gold standard for detection of PTEN sequence abnormalities. However, this approach fails to address the epigenetic mechanisms that contribute to functional PTEN loss. Using a study cohort of 154 endometrioid and non-endometrioid endometrial carcinomas, we performed full-length PTEN sequencing and PTEN immunohistochemistry on each tumor. PTEN sequence abnormalities were detected in a significantly lower proportion of cases (43%) than PTEN protein loss (64%, P=0.0004). Endometrioid tumors had a significantly higher proportion of PTEN sequence abnormalities and PTEN protein loss than non-endometrioid tumors. Within the latter group, PTEN sequence abnormalities and PTEN protein loss were most frequent in undifferentiated carcinomas, followed by mixed carcinomas; they were least frequent in carcinosarcomas. Overall, at least one PTEN sequence abnormality was detected in each exon, and the greatest number of sequence abnormalities was detected in exon 8. Pure-endometrioid tumors had a significantly higher frequency of sequence abnormalities in exon 7 than did the non-endometrioid tumors (P=0.0199). Importantly, no mutational hotspots were identified. While PTEN protein loss by immunohistochemistry was identified in 89% of cases with a PTEN sequence abnormality, PTEN protein loss was detected by immunohistochemistry in 44% of cases classified as PTEN wild type by sequencing. For the first time, we demonstrate that PTEN immunohistochemistry is able to identify the majority of cases with functional PTEN loss. However, PTEN immunohistochemistry also detects additional cases with PTEN protein loss that would otherwise be undetected by gene sequencing. Therefore, for clinical purposes, immunohistochemistry appears to be a preferable technique for identifying endometrial tumors with loss of PTEN function. PMID- 22301703 TI - Loss of ARID1A/BAF250a-expression in endometriosis: a biomarker for risk of carcinogenic transformation? AB - Mutations of the tumor-suppressor gene ARID1A result in the loss of protein expression of the BRG-associated factor 250a (BAF250a), a large subunit of transcription-regulating Human SWI/SNF complexes, which have an important role in the control of cell proliferation and tumor suppression. ARID1A mutations are particularly frequent in endometriosis-associated ovarian clear cell and endometrioid carcinomas, and were recently described as a possible key mechanism and early step in the transformation of endometriosis into cancer. Here, we examined the immunohistochemical expression pattern of BAF250a in a tissue microarray including 74 endometriosis and 30 endometrium samples. Ovarian cancer samples (n=136) served as a control. Epithelial BAF250a expression was assessable in 90/104 (87%) and stromal BAF250a expression in 95/104 (91%) of the endometriosis, and endometrium cases due to lack of adequate tissue in some spots. Complete lack of BAF250a expression was observed in three endometriomas (n=3/20, 15%) and one deep-infiltrating endometriosis sample (n=1/22, 5%), but in none of the peritoneal endometriosis (n=0/16) and eutopic endometrium samples (n=0/30). A comparison of the mean immunoreactivity scores revealed a significantly lower expression rate of BAF250a in endometriomas compared with normal endometrium (P<0.0005), as well as peritoneal (P=0.003) and deep infiltrating endometriosis (P=0.02). Our data demonstrates that a complete loss of BAF250a expression is observable in some endometriotic lesions, especially in endometriomas. In addition, we report that a partial loss of BAF250a expression is occurring in the form of cell clusters indicating a clonal loss of BAF250a expression in these cells. The loss of expression of the tumor-suppressor protein BAF250a in some endometriomas possibly indicates a risk of malignant transformation in these cases, which could be of importance in the determination of individual treatment strategies. However, its role and value as a prognostic parameter in endometriosis needs to be further studied. PMID- 22301704 TI - Semi-quantitative immunohistochemical assay versus oncotype DX((r)) qRT-PCR assay for estrogen and progesterone receptors: an independent quality assurance study. AB - Estrogen receptor (ER) status is a strong predictor of response to hormonal therapy in breast cancer patients. Presence of ER and level of expression have been shown to correlate with time to recurrence in patients undergoing therapy with tamoxifen or aromatase inhibitors. Risk reduction is also known to occur in ER-negative, progesterone receptor (PR)-positive patients treated with hormonal therapy. Since the 1990s, immunohistochemistry has been the primary method for assessing hormone receptor status. Recently, as a component of its oncotype DX((r)) assay, Genomic Health began reporting quantitative estrogen and PR results determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). As part of an ongoing quality assurance program at our institution, we reviewed 464 breast cancer cases evaluated by both immunohistochemistry and oncotype DX((r)) assay for estrogen and PR. We found good correlation for ER status between both assays (98.9% concordance), with immunohistochemistry being slightly more sensitive. Concordance for PR was 94.2% between immunohistochemistry and qRT-PCR with immunohistochemistry again more sensitive than RT-PCR. The results also showed linear correlation between immunohistochemistry H-scores and qRT-PCR expression values for ER (correlation coefficient of 0.579), and PR (correlation coefficient of 0.685). Due to the higher sensitivity of hormone receptor immunohistochemistry and additional advantages (ie preservation of morphology, less expensive, faster, more convenient), we conclude immunohistochemistry is preferable to qRT-PCR for determination of estrogen and PR expression. PMID- 22301705 TI - Reproducibility of endometrial intraepithelial neoplasia diagnosis is good, but influenced by the diagnostic style of pathologists. AB - Endometrial intraepithelial neoplasia (EIN) applies specific diagnostic criteria to designate a monoclonal endometrial preinvasive glandular proliferation known from previous studies to confer a 45-fold increased risk for endometrial cancer. In this international study we estimate accuracy and precision of EIN diagnosis among 20 reviewing pathologists in different practice environments, and with differing levels of experience and training. Sixty-two endometrial biopsies diagnosed as benign, EIN, or adenocarcinoma by consensus of two expert subspecialty pathologists were used as a reference comparison to assess diagnostic accuracy of 20 reviewing pathologists. Interobserver reproducibility among the 20 reviewers provided a measure of diagnostic precision. Before evaluating cases, observers were self-trained by reviewing published textbook and/or online EIN diagnostic guidelines. Demographics of the reviewing pathologists, and their impressions regarding implementation of EIN terminology were recorded. Seventy-nine percent of the 20 reviewing pathologists' diagnoses were exactly concordant with the expert consensus (accuracy). The interobserver weighted kappa values of 3-class EIN scheme (benign, EIN, carcinoma) diagnoses between expert consensus and each of reviewing pathologists averaged 0.72 (reproducibility, or precision). Reviewing pathologists demonstrated one of three diagnostic styles, which varied in the repertoire of diagnoses commonly used, and their nonrandom response to potentially confounding diagnostic features such as endometrial polyp, altered differentiation, background hormonal effects, and technically poor preparations. EIN diagnostic strategies can be learned and implemented from standard teaching materials with a high degree of reproducibility, but is impacted by the personal diagnostic style of each pathologist in responding to potential diagnostic confounders. PMID- 22301706 TI - Inclusion and exclusion in nutrigenetics clinical research: ethical and scientific challenges. AB - BACKGROUND/AIMS: There are compelling reasons to ensure the participation of ethnic minorities and populations of all ages worldwide in nutrigenetics clinical research. If findings in such research are valid for some individuals, groups, or communities, and not for others, then ethical questions of justice--and not only issues of methodology and external validity--arise. This paper aims to examine inclusion in nutrigenetics clinical research and its scientific and ethical challenges. METHODS: In total, 173 publications were identified through a systematic review of clinical studies in nutrigenetics published between 1998 and 2007. Data such as participants' demographics as well as eligibility criteria were extracted. RESULTS: There is no consistency in the way participants' origins (ancestry, ethnicity, or race) and ages are described in publications. A vast majority of the studies identified was conducted in North America and Europe and focused on 'white' participants. Our results show that pregnant women (and fetuses), minors, and the elderly (>= 75 years old) remain underrepresented. CONCLUSION: Representativeness in nutrigenetics research is a challenging ethical and scientific issue. Yet, if nutrigenetics is to benefit whole populations and be used in public and global health agendas, fair representation as well as clear descriptions of participants in publications are crucial. PMID- 22301707 TI - Acoustofluidics 6: Experimental characterization of ultrasonic particle manipulation devices. AB - Because of uncertainties in material and geometrical parameters in ultrasonic devices, experimental characterization is an indispensable part in their successful application for the manipulation of particles or cells. Its miniaturized size precludes the use of many of the usual tools used for macroscopic systems. Also, a further challenge is the fact that the resulting motion due to the electromechanical actuation has both high frequency and small amplitudes. Contactless methods like laser interferometry are therefore promising methods. In addition, as long as there is strong electromechanical coupling between the transducer and the device also electrical measurements like admittance curves give insight into the frequencies at which the devices might work best. This is the case for example for piezoelectric transducers working at one of their resonance frequencies. Because the devices usually are used in resonant modes, narrow frequency detection methods like lock in amplifiers help to improve the signal to noise ratio. Also many analysis tools have been established in the context of modal analysis, which is based on frequency domain methods. Special emphasis is placed here on the determination of the quality factor Q of the resonator, as Q determines the efficiency of a device. PMID- 22301708 TI - Lead growth on Si(111) surfaces reconstructed by indium. AB - We study the Pb growth on both ?3 * ?3-In and 4 * 1-In reconstructed Si(111) surfaces at room and low temperature (160 K). The study takes place with complementary techniques, to investigate the role of the substrate reconstruction and temperature in determining the growth mode of Pb. Specifically, we focus on the correlation between the growth morphology and the electronic structure of the Pb films. The information is obtained by using Auger electron spectroscopy, low energy electron diffraction, soft x-ray photoelectron spectroscopy, scanning tunneling microscopy and spot profile analysis-low energy electron diffraction. The results show that, at low temperature and coverage <=12 ML on the Si(111)?3 * ?3-In surface, Pb does not alter the initial semiconducting character of the substrate and three-dimensional Pb islands with poor crystallinity are grown on a wetting layer. On the other hand, for the same coverage range, Pb growth on the Si(111)4 * 1-In surface results in metallic Pb(111) crystalline islands after the completion of a double incomplete wetting layer. In addition, the bond arrangement of the adatoms is studied, confirming that In adatoms interact more strongly with the silicon substrate than the Pb ones. This promotes a stronger Pb Pb interaction and enhances metallization. The onset of the metallization is correlated with the amount of pre-deposited In on the Si(111) surface. The decoupling of the Pb film from the 4 * 1-In interface can also explain the unusual thermal stability of the uniform height islands observed on this interface. The formation of these Pb islands is driven by quantum size effects. Finally, the different results of Pb growth on the two reconstructed surfaces confirm the importance of the interface, and also that the growth morphology, as well as the electronic structure of the Pb film can be tuned with the initial substrate reconstruction. PMID- 22301709 TI - Does parental involvement make a difference in school-based nutrition and physical activity interventions? A systematic review of randomized controlled trials. AB - OBJECTIVES: Parental involvement is often advocated as important for school-based interventions, however, to date, only inconsistent evidence is available. Therefore, this study aimed at determining the impact of parental involvement in school-based obesity prevention interventions in children and adolescents. METHODS: A systematic review of obesity prevention studies published from 1990 to 2010 including a comparison between school-based interventions with and without parental component was conducted. Only studies reporting effects on health behaviour-related outcomes were included. RESULTS: Some positive effects of parental involvement were found on children's behaviours and behavioural determinants. Parental modules including different strategies and addressing several home-related determinants and parenting practices concerning eating and physical activity behaviours were more likely to be effective. However, no conclusive evidence could be provided concerning the added value of parent involvement, because of the paucity of studies to test this hypothesis. The few studies that are available provide inconsistent evidence. CONCLUSIONS: There is a need for more studies comparing school-based interventions with and without a parental component, and dose, strategies and content of parental components of school-based interventions should be better reported in articles. PMID- 22301710 TI - Salmonella enterotoxin (Stn) regulates membrane composition and integrity. AB - The mechanism of action of Salmonella enterotoxin (Stn) as a virulence factor in disease is controversial. Studies of Stn have indicated both positive and negative effects on Salmonella virulence. In this study, we attempted to evaluate Stn function and its effects on Salmonella virulence. To investigate Stn function, we first performed in vitro and in vivo analysis using mammalian cells and a murine ileal loop model. In these systems, we did not observe differences in virulence phenotypes between wild-type Salmonella and an stn gene-deleted mutant. We next characterized the phenotypes and molecular properties of the mutant strain under various in vitro conditions. The proteomic profiles of the total cell membrane protein fraction differed between wild type and mutant in that there was an absence of a protein in the mutant strain, which was identified as OmpA. By far-western blotting, OmpA was found to interact directly with Stn. To verify this result, the morphology of Salmonella was examined by transmission electron microscopy, with OmpA localization being analyzed by immunogold labeling. Compared with wild-type Salmonella, the mutant strain had a different pole structure and a thin periplasmic space; OmpA was not seen in the mutant. These results indicate that Stn, via regulation of OmpA membrane localization, functions in the maintenance of membrane composition and integrity. PMID- 22301711 TI - Continual low-level MEK inhibition ameliorates cardio-facio-cutaneous phenotypes in zebrafish. AB - Cardio-facio-cutaneous (CFC) syndrome is caused by germline mutations in KRAS, BRAF and MEK1/2. The highly selective and potent MEK inhibitors that have been developed as anti-cancer agents hold potential as therapeutics for CFC syndrome. We have previously shown that the effects of CFC mutations on zebrafish gastrulation can be prevented by a 1-hour treatment with MEK inhibitors within a specific developmental time-window. However, MEK activity is essential for normal development and PD0325901 treatment outside this treatment window leads to additional developmental defects in MEK-dependent tissues. We now test ten different doses of PD0325901 at six developmental time points and assess the effects on body axis length, heart development and craniofacial structures in zebrafish embryos. Notably, we find that a continuous low-level dose of PD0325901 that has only minor inhibition of MEK activity can prevent the action of both the common CFC BRAF(Q257R) kinase-active allele and the BRAF(G596V) kinase-impaired mutant allele through the first 5 days of development. These results provide a detailed study of the effects of PD0325901 in development and show that, unlike in cancer, which requires robust inhibition of MAPK signalling, a partial reduction in phospho-ERK1/2 activity is sufficient to moderate the developmental effects of BRAF(CFC) mutations. PMID- 22301712 TI - Controlling formation of silver/carbon nanotube networks for highly conductive film surface. AB - Flexible polymer films with high electrical conductivity were prepared through a simple coating of well-dispersed silver nanoparticle (AgNP) and multiwalled carbon nanotube (CNT) solution. The hybrid film with surface resistance as low as 1 * 10(-2) Omega/sq was prepared by controlling the annealing temperature in air and by using a suitable composition of silver nitrate/CNT/poly(oxyethylene) oligo(imide) (POE-imide) in the ratio 20:1:20 by weight. During the heating, color of the film surface changed from black to golden to milky white, indicating the accumulation of AgNPs through surface migration and melting into CNT connected networks. Thermogravimetric measurements showed that the transition temperature of 170 degrees C was responsible for the POE-imide degeneration and the subsequent Ag melting with a decrease in the surface resistance from 2.1 * 10(5) to 2.0 * 10(-1) Omega/sq, which was able to illuminate light-emitting diode lamps because of the formation of a continuous Ag network. PMID- 22301713 TI - Electrochemical immunoassay on a 3D microfluidic paper-based device. AB - A high-throughput, simple, fast, low-cost and sensitive paper-based electrochemical immunodevice has been demonstrated based on a functionalized 3D paper-based device for point-of-care diagnosis. PMID- 22301714 TI - Novel biomarkers in cardiovascular disease: research tools or ready for personalized medicine? AB - In recent years, a wide range of novel biomarkers have been evaluated for different cardiovascular disease states (eg, ischemia, congestion, and physiological stress), and many have shown promising results for the prediction of cardiovascular end points. However, to become useful for clinicians and to allow for personalized medicine, each novel biomarker must fulfill 3 fundamental criteria: (1) it must be easy to measure; (2) it must provide new information; and (3) it must help the clinician to manage patients. Although many biomarkers may be useful for prognostication, very few have been shown to improve the treatment of patients with cardiovascular disease when implemented in a clinical setting. PMID- 22301715 TI - Review of radiation reduction strategies in clinical cardiovascular imaging. AB - The use of ionizing radiation for medical diagnostic tests and interventional procedures has grown substantially over the past 2 decades, and there is now considerable concern expressed in both the medical literature and the lay press of the harmful effects of radiation exposure. Although there is some controversy regarding whether this medical radiation is actually harmful, minimizing the dose to the patient is logical and a basic part of proper care. To do this, clinicians must have an understanding of the amount of radiation that is involved with each test. Physicians have a responsibility to keep the level of radiation exposure as low as reasonably achievable. A number of simple and common sense measures can help achieve this goal. Encouragingly, there are also numerous new technologies which can substantially lower radiation dose, especially in cardiovascular studies. This review will highlight various ways to reduce radiation in cardiovascular imaging. PMID- 22301716 TI - Cervical carotid artery dissection: current review of diagnosis and treatment. AB - Carotid artery dissection is a cause of stroke, especially in young and middle aged patients. A dissection occurs when there is an intimal tear or rupture of the vasa vasorum, leading to an intramural hematoma, which is thought to result from trauma or can occur spontaneously, and is likely multifactorial, involving environmental and intrinsic factors. The clinical diagnosis of carotid artery dissection can be challenging, with common presentations including pain, partial Horner syndrome, cranial nerve palsies, or cerebral ischemia. With the use of noninvasive imaging, including magnetic resonance and computed tomography angiography, the diagnosis of carotid dissection has increased in frequency. Treatment options include thrombolysis, antiplatelet or anticoagulation therapy, endovascular or surgical interventions. The choice of appropriate therapy remains controversial as most carotid dissections heal on their own and there are no randomized trials to compare treatment options. PMID- 22301717 TI - Cardiovascular pharmacologic therapies under investigation: 2012. AB - Cardiovascular (CV) diseases and cerebrovascular diseases remain major causes of mortality and morbidity in the United States. Intensive efforts over the past 45 years to develop important pharmacologic treatments have reduced CV risk dramatically. Described in this article are over 150 drugs being developed to prevent and treat CV disease. PMID- 22301718 TI - Combination of biomarkers: PET [18F]flutemetamol imaging and structural MRI in dementia and mild cognitive impairment. AB - BACKGROUND: The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Abeta accumulation and neuronal degeneration or injury. OBJECTIVE: It was the aim of this study to compute hippocampus volume from MRI and a neocortical standard uptake value ratio (SUVR) from [(18)F]flutemetamol PET and investigate the performance of these biomarkers when used individually and when combined. METHODS: Fully automated methods for hippocampus segmentation and for computation of neocortical SUVR were applied to MR and scans with the investigational imaging agent [(18)F]flutemetamol in a cohort comprising 27 AD patients, 25 healthy volunteers (HVs) and 20 subjects with amnestic mild cognitive impairment (MCI). Clinical follow-up was performed 2 years after the initial assessment. RESULTS: Hippocampus volumes showed extensive overlap between AD and HV cases while PET SUVRs showed clear group clustering. When both measures were combined, there was a relatively compact cluster of HV scans and a less compact AD cluster. MCI cases had a bimodal distribution of SUVRs. [(18)F]Flutemetamol-positive MCI subjects showed a large variability in hippocampus volumes, indicating that these subjects were in different stages of neurodegeneration. Some [(18)F]flutemetamol-negative MCI scans had hippocampus volumes that were well below the HV range. Clinical follow-up showed that 8 of 9 MCI to AD converters came from the [(18)F]flutemetamol-positive group. CONCLUSION: Combining [(18)F]flutemetamol PET with structural MRI provides additional information for categorizing disease and potentially predicting shorter time to progression from MCI to AD, but this has to be validated in larger longitudinal studies. PMID- 22301719 TI - Correlation between bladder volume and irradiated dose of small bowel in CT-based planning of intracavitary brachytherapy for cervical cancer. AB - OBJECTIVE: To quantify the effect of bladder volume on the dose distribution of intracavitary brachytherapy in computed tomography-based treatment planning for cervical cancer. METHODS: Ten patients with cervical cancer were treated with high-dose rate radiation brachytherapy. For the three-dimensional analysis, pelvic computed tomographic scans were obtained from patients with indwelling catheters in place and from patients who received 50, 100, 150 and 200 cc injections of sterile water into their bladders ('200 cc' was defined as a full bladder). Additionally, scans were made in the prone position with the full bladder. RESULTS: Bladder fullness significantly affected the dose to the small bowel and bladder. The median of maximal doses to the small bowel was significantly greater with an empty bladder in all factors of hot spot (480 vs. 256 cGy on D-2cc). Although dosimetry revealed lower doses for larger volumes of bladder (D-50 and V-25%), the median maximal dose to the bladder was significantly greater with a full bladder (420 vs. 775 cGy on D-2cc). The rectosigmoid doses were not affected by bladder distension (476 vs. 467 cGy on D 2cc). After changing to the prone position, the hot spot dose of small bowel did not change but that of the bladder significantly decreased, although this procedure was very difficult. CONCLUSIONS: An increase in bladder volume resulted in a significant reduction in the hot spot dose of the small bowel at the expense of an increase in that of the bladder without changing the dose distribution of the rectosigmoid. PMID- 22301720 TI - A series of isostructural mesoporous metal-organic frameworks obtained by ion exchange induced single-crystal to single-crystal transformation. AB - A series of metal-organic frameworks representing a non-interpenetrated framework analogue of MOF-14 have been synthesized by using two different linkers, 4,4',4'' benzene-1,3,5-triyl-benzoic acid (H(3)BTB) and 4,4'-bipyridine (Bpy). Interestingly, the transition metal ions in the paddle-wheel metal clusters could be exchanged by other transition metal ions via a direct single-crystal to single crystal transformation. This post-synthesis route can be used for synthesis of isomorphous metal-organic frameworks that cannot be obtained by direct synthesis. PMID- 22301721 TI - Understanding the mechanism of the intramolecular stetter reaction. A DFT study. AB - The mechanism of the N-heterocyclic carbene (NHC)-catalyzed intramolecular Stetter reaction of salicylaldehyde 1 to yield chromanone 3 has been theoretically studied at the B3LYP/6-31G** level. This NHC-catalyzed reaction takes place through six elementary steps, which involve: (i) formation of the Breslow intermediate IN2; (ii) an intramolecular Michael-Type addition in IN2 to form the new C-C s bond; and (iii) extrusion of the NHC catalyst from the Michael adduct to yield chromanone 3. Analysis of the relative free energies in toluene indicates that while formation of Breslow intermediate IN2 involves the rate determining step of the catalytic process, the intramolecular Michael-type addition is the stereoselectivity determining step responsible for the configuration of the stereogenic carbon a to the carbonyl of chromanone 3. An ELF analysis at TSs and intermediates involved in the Michael-type addition allows for the characterization of the electronic changes along the C-C bond-formation. PMID- 22301722 TI - Sustained growth of the impact factors of MDPI open access journals. AB - Following the tradition established during the past two years, we are pleased to report the newly released Impact Factors of MDPI open access journals by the means of an editorial. This year's edition of the Journal Citation Reports (JCR), which is published annually by Thomson Reuters, includes seven journals published by MDPI, including three that received their first official Impact Factors- Energies, Entropy, and more surprisingly Viruses--the latest with citation data from 2009 only. We are pleased to announce that the continued growth in Impact Factors reported during the past two years has been sustained, and Impact Factors of MDPI journals continue on a growth path. Table 1 reports the latest Impact Factors for 2010. Figure 1 graphically depicts the evolution of the Impact Factors for the four MDPI open access journals that have received Impact Factors in the past. Table 2 reports the ranking of the MDPI journals within the subject categories of the Science Citation Index Expanded (SCIE). PMID- 22301723 TI - Design, synthesis and anti-fibrosis activity study of N1-substituted phenylhydroquinolinone derivatives. AB - Pirfenidone (5-methyl-1-phenyl-2(1H)-pyridone, PFD) is a small-molecule compound acting on multiple targets involved in pathological fibrogenesis and is effective to increase the survival of patients with fibrosis, such as idiopathic pulmonary fibrosis. However, PFD is not active enough, requiring a high daily dose. In this study, to keep the multiple target profiles, N1-substituted phenylhydroquinolinone derivatives, which retain the 1-phenyl-2(1H)-pyridone scaffold were designed and synthesized. The preliminary anti-fibrosis activities for all target compounds were evaluated on a NIH3T3 fibroblast cell line using MTT assay methods. Most compounds showed significant inhibition on NIH3T3 cell proliferation with a IC50 range of 0.09-26 mM, among which 5-hydroxy-1-(4' bromophenyl)-5,6,7,8-tetrahydroquinolin-2(1H)-one (6j) displayed 13 times higher potency (IC50 = 0.3 mM) than that of AKF-PD (IC50 = 4.2 mM). These results suggest that N1-substituted phenylhydroquinolinone is a promising scaffold which can be applied for further investigation and for developing novel anti-fibrosis agents. PMID- 22301724 TI - Conformationally restricted dynamic supramolecular catalysts for substrate selective epoxidations. AB - A second generation of a substrate-selective dynamic supramolecular catalytic system consisting of a catalyst part and a receptor part, connected by a hydrogen bonding motif, has been realized based on rational design. The results from analyses of the equilibrium mixture of the species generated by the components of the first generation system led us to selectively lock the cisoid conformation of the catalyst part to increase the amount of the substrate-selective catalytic cavity in the equilibrium mixture. This was realized by strapping the catalyst part by organic synthesis. This strapping led to an increase in substrate selectivity in the pair-wise competitive epoxidations of pyridyl- vs. phenyl appended styrenes and pyridyl- vs. phenyl-appended stilbenes of both Z- and E- configuration compared to the first generation system, reaching 3.4 : 1 as the highest substrate selectivity for Z-mono-pyridyl-stilbene (27a) vs. the corresponding all-carbon analogue (28a) and for E-dipyridyl-stilbene (26b) vs. the corresponding all-carbon analogue (28b), respectively. PMID- 22301725 TI - Social effectiveness therapy (SET-C) in a boy with Asperger's syndrome: a case report. PMID- 22301726 TI - Hypertrophic cardiomyopathy and planned in vitro fertilization. Genetic testing and clinical evaluation. AB - Hypertrophic cardiomyopathy (HCM) is often transmitted to the offspring of affected individuals. This case report describes the role of genetic screening in a 39-year-old woman with a family history of sudden cardiac death. The patient wished to become pregnant and was seeking medical consultation. In addition to electro- and echocardiograms, genomic DNA was isolated and direct sequencing was employed to screen the patient for some of the most common genes that cause HCM. A pathogenic heterozygous mutation c.700 g > a p.Arg186Gln in TNNI3 was identified, which was not found in 200 normal control chromosomes. Mutation specific genetic testing was also performed in four family members, and the same mutation was absent. Genetic screening appears cost effective in familiar members with a known mutation, provides important information about the affected individual, and can facilitate the future management of family members and offspring. PMID- 22301727 TI - [Hereditary cardiac amyloidosis with transthyretin mutations. A cause of sudden death ]. AB - Hereditary amyloidoses present a clinically and genetically heterogeneous group of autosomal dominant diseases. The most frequent form is associated with mutations of the transthyretin gene. The type of mutation determines the process, the organs primarily involved as well as the time of onset of the disease. Life expectancy is generally limited by the degree of cardiomyopathy. The cases of two male patients who died suddenly and unexpectedly are presented. In both cases, autopsy revealed a biventricular cardiac hypertrophy. Cardiac amyloidosis was diagnosed by means of histologic and genetic analysis. Early diagnosis is essential for those affected, since liver transplantation still represents the only effective treatment. This illustrates the benefit of autopsy investigations for surviving relatives, who may themselves be affected by the disease. PMID- 22301728 TI - Acute inferior myocardial infarction in a young female patient with polyarteritis nodosa. AB - Coronary involvement of polyarteritis nodosa (PAN) has been mostly identified in postmortem studies. We report a case with inferior myocardial infarction (MI) because of coronary dissection and thrombosis in PAN. A 23-year-old woman with chest pain was admitted to the emergency department. The admission ECG was suggestive of inferior MI with no right ventricular infarction. Coronary angiography revealed an occluded right coronary artery because of coronary dissection and concomitant thrombosis. Coronary angioplasty and stent implantation were performed successfully without complications. This report emphasizes the importance of PAN in spontaneous coronary dissection and thrombosis even in young patients. PMID- 22301729 TI - [Patients suffering from atrial fibrillation in Germany. Characteristics, resource consumption and costs]. AB - INTRODUCTION: Atrial fibrillation (Afib) is considered to be the most frequent form of cardiac dysrhythmia and is well known as a key risk factor for arterial thromboembolism. The incidence of Afib will increase in the future due to demographic changes as well as improved treatment options for acute and chronic heart diseases. OBJECTIVE: The primary objectives of this analysis were to describe patient characteristics, to assess the resource consumption associated with Afib and to measure costs of direct treatment as well as consequential costs. A secondary objective was to identify factors that influence the costs or the type of Afib. METHODS: The analysis is based on the representative ATRIUM register (Ambulantes Register zur Morbiditat des Vorhofflimmerns, Ambulatory register on morbidity of atrial fibrillation), a prospective, multicenter cohort study in which general practitioners and family doctors documented the characteristics and resource utilization of consecutively enrolled patients. The documented resource consumption use was subsequently valued with unit costs. The presented results are focused on the baseline documentation and refer to the period 12 months before enrollment. RESULTS: A total of 3,667 patients (mean age 72.1+/-9.2 years, 58% men) fulfilled all inclusion criteria and were included by a total of 730 doctors. The patients had an average of 2.4+/-1.0 risk factors and the most common was hypertension (84% of patients). The most commonly observed comorbidities were heart failure (43%) and coronary heart disease (CHD, 35%). Medicines for oral anticoagulation (86%) and beta blockers (75%) were the most frequently prescribed drugs. A total of 1/3 of all patients received a specific kind of Afib therapy (e. g. drug conversion, cardioversion) during the past 12 months. The disease-specific mean costs of the patients were 3,274+/-5,134 Euro, while the acute (inpatient) treatment represented the largest proportion of these total costs (1,639+/-3,623 Euro). Patients with high treatment costs were significantly younger and suffered from more concomitant diseases. CONCLUSION: Atrial fibrillation is associated with significant patient-related attributable costs that are caused particularly by expenditures of inpatient stay. New, innovative treatment strategies seem to offer particular potential savings if they are able to reduce the number of hospitalizations due to Afib itself or subsequent cardiac events. PMID- 22301730 TI - [Mitral valve surgery in patients with extensively calcified mitral annulus: long term echocardiographic and clinical follow-up]. AB - OBJECTIVE: The aim of this study was the analysis of long-term results in patients with hemodynamically significant mitral valve disease due to extensively calcified mitral annulus who underwent decalcification and patch reconstruction. PATIENTS AND METHODS: Between 1996 and 2008 a total of 109 patients underwent surgery for extensive calcification and severe mitral insufficiency and mitral stenosis. The mean age of the patients (65 women and 44 men) was 66.4 +/- 13.8 years. In 53 patients (49%) mitral valve repair was performed and the remaining 56 patients (51%) received a mitral valve replacement. Of the patients 64 (59%) required concomitant surgery. The mean follow up time was 96 +/- 48 months. RESULTS: The in-hospital and late mortality was 8.3% (9 patients) and 25.6% (28 patients), respectively. The actuarial survival rates at 5, 8 and 12 years were 88.1%, 76.2% and 66.1%, respectively. Echocardiographic follow-up presented a mitral insufficiency grade III in 4 patients (6%). None of the patients had a mitral insufficiency grade IV. A significant reduction of left atrium diameter, of the LVEDD as well as the mean transvalvular gradient was observed. Freedom from reoperation at 5 and 8 years was 96.4% and 91.8%, respectively. Systemic hypertension, diabetes mellitus, age older than 65 years, concomitant aortic valve replacement, concomitant procedures, chronic renal insufficiency and cardiac decompensation in the medical history were found to be predictors for significantly increased early or late mortality. CONCLUSION: The long-term results strongly suggest that en bloc decalcification and patch reconstruction of the mitral annulus can be safely undertaken in high risk patients. PMID- 22301731 TI - Health economic evaluation of the use of drug-eluting stents : First results from the Drug-Eluting Stent Registry (DES.de). AB - OBJECTIVE: The purpose of the economic evaluation of the German Drug-Eluting Stent (DES) registry includes the investigation of the economic impact and cost effectiveness of DES compared to bare-metal stents (BMS) and between paclitaxel eluting (PES) and sirolimus-eluting stents (SES). Here, methodology and initial results are presented. METHODS: Patients were recruited in 2005 and 2006 in 87 centres across Germany. Selection of PES, SES, or BMS was made at the discretion of the cardiologists in charge. Clinical, economic, and quality of life (QoL) data were collected at baseline and up to 12 months. Group comparisons were conducted using Fisher's exact and t test. RESULTS: Overall, 3,930 patients were enrolled: 3,471 (75% male, 65 +/- 11 years) received DES and 458 (74% male, 67 +/ 11 years) BMS. Among the DES patients, 1,821 received PES (75% male, 65 +/- 10 years) and 1,600 SES (76% male, 65 +/- 11 years). There were baseline differences in clinical and procedural characteristics but not in QoL. During the hospital stay, major adverse cardiac and cerebrovascular events occurred in 1.6% of DES (PES 1.9%, SES 1.1%) and 2.2% of BMS patients (BMS vs. DES, PES, and SES p = 0.327, 0.706, and 0.098, respectively). Hospital treatment costs were 4,989 +/- 1,284 and 3,609 +/- 924 , respectively, in DES and BMS patients (p < 0.001) with no significant difference between PES and SES. CONCLUSION: The economic evaluation of the large DES registry demonstrates increased initial hospitalisation costs associated with DES compared to BMS. Further analysis of the economic impact and cost-effectiveness of DES will provide estimates on large "real world" patient populations for decision makers and aid in reimbursement decisions of DES within the German and other health care systems. PMID- 22301732 TI - Coexistence of congenital heart anomalies with noncompaction of the ventricular myocardium. Two case reports. AB - Noncompaction of the ventricular myocardium (NVM) is a rare cardiac anomaly which can lead to the development of cardiomyopathy. NVM can be isolated or associated with congenital heart anomalies such as ventricular septal defect, atrial septal defect, pulmonic stenosis, bicuspid aortic valve, and Ebstein anomaly. NVM usually presents with heart failure symptoms, ventricular tachyarrhythmias, and thromboembolic events. We report two cases of NVM, one associated with a ventricular septal defect and other associated with bicuspid aortic valve. PMID- 22301733 TI - Pannexin protein expression in the rat middle cerebral artery. AB - BACKGROUND: Connexin proteins are well known to participate in cell-to-cell communication within the cerebral vasculature. Pannexins are a recently discovered family of proteins that could potentially be involved in cell-to-cell communication. Herein, we sought to determine whether pannexins are expressed in rat middle cerebral artery (MCA). METHODS: A combination of RT-PCR, immunoblotting and immunohistochemistry techniques was used to characterize the expression pattern of pannexins in rat MCA. A fluorescent dye uptake approach in cultured smooth muscle cells was used to determine whether these cells have functional hemichannels. RESULTS: We report for the first time that pannexins are expressed in the cerebral vasculature. We reveal that pannexin 1 is expressed in smooth muscle but not in endothelium and pannexin 2 is expressed in both endothelium and smooth muscle. Fluorescent dye entered cultured smooth muscle cells in the absence of extracellular calcium or when the cells were depolarized, which was prevented by the putative hemichannel blocker carbenoxolone. CONCLUSIONS: The identification of pannexins in rat MCA indicates that pannexin expression is not restricted to neuronal cells. Dye uptake in cultured smooth muscle cells exhibited properties similar to those of connexin and pannexin hemichannels, which may represent another form of cell-to-cell communication within the vasculature. PMID- 22301734 TI - The role of S100a9 in the pathogenesis of Alzheimer's disease: the therapeutic effects of S100a9 knockdown or knockout. AB - Neuroinflammation is one of the important pathogenic features of Alzheimer's disease (AD). Recently, S100a9 was found to be increased within neuritic plaques and reactive glia and was proposed to participate in the inflammation associated with the pathogenesis of AD. Our study showed that S100a9 expression was increased in the brains of AD mice and AD patients. In Tg2576 mice, knockdown by short hairpin RNA or knockout of the S100a9 gene significantly reduced the neuropathology, greatly improved the learning and memory impairment and reduced the amount of Abeta and APP-CTs by increasing neprilysin and decreasing BACE activity. These results clearly show that the upregulation of the S100a9 gene plays an important role in the neuropathology and memory impairment in AD, suggesting that the knockdown and knockout of this gene have a great therapeutic potential for AD. PMID- 22301735 TI - Microfluidic nanoplasmonic-enabled device for multiplex DNA detection. AB - We describe a rapid, quantitative, multiplex, self-labelled, and real-time DNA biosensor employing Ag nanoparticle-bound DNA hairpin probes immobilized in a microfluidic channel. Capture of complementary target DNAs by the microarrayed DNA hairpin probes results in a positive fluorescence signal via a conformational change of the probe molecules, signalling the presence of target DNAs. The device's capability for quantitative analyses was evaluated and a detection time as low as 6 min (with a target flow rate of 0.5 MUl min(-1)) was sufficient to generate significant detection signals. This detection time translates to merely 3 MUl of target solution consumption. An unoptimized sensitivity of 500 pM was demonstrated for this device. PMID- 22301764 TI - The presence of a (1 * 1) oxygen overlayer on ZnO(0001) surfaces and at Schottky interfaces. AB - The atomic surface and interface structures of uncoated and metal-coated epi polished ZnO(0001) Zn-polar wafers were investigated via surface x-ray diffraction. All uncoated samples showed the presence of a fully occupied (1 * 1) overlayer of oxygen atoms located at the on-top position above the terminating Zn atom, a structure predicted to be unstable by several density functional theory calculations. The same oxygen overlayer was clearly seen at the interface of ZnO with both elemental and oxidized metal Schottky contact layers. No significant atomic relaxations were observed at surfaces and interfaces processed under typical device fabrication conditions. PMID- 22301765 TI - Synthesis of stable AuAg bimetallic nanoparticles encapsulated by diblock copolymer micelles. AB - We present a facile method for the preparation of bimetallic AuAg nanoparticles (NPs) with controlled size and composition rendering them ideally suitable for optical and catalytic applications. In analogy to methods for the generation of monometallic Au and Ag NPs, AuAg NPs were prepared inside polystyrene-b-poly(4 vinylpyridine) (PS-b-P4VP) block-copolymer micelles formed in toluene, by loading the P4VP cores of the micelles first with AgNO(3) and then with HAuCl(4). In contrast to the reverse sequence of loading, homogenously bimetallic AuAg particle arrays were achieved after reduction carried out in solution with hydrazine monohydrate as the reducing agent. TEM reveals that stable and spherical NPs can be prepared well separated from one another and with a narrow size distribution with diameters of ~3 nm. The bimetallic NP composition was confirmed by energy-dispersive X-ray spectroscopy (EDX) of single NPs. The atomic ratio of Ag and Au contained in single particles is in good agreement with the relative concentrations of both metals used in the synthesis which was confirmed by atomic absorption spectroscopy. The atomic ratio Au : Ag was systematically varied between 3 : 1 and 1 : 3. For all ratios UV-vis spectra showed a single plasmon band. Its wavelength varied from 430 for Au : Ag = 1 : 3 to 515 nm for Au : Ag = 3 : 1, showing a linear dependence on the relative amount of gold within the range of plasmon wavelengths from monometallic gold (538 nm) to silver (415 nm). PMID- 22301766 TI - Effects of n-3 fatty acids on major cardiovascular events in statin users and non users with a history of myocardial infarction. AB - AIMS: Recent secondary prevention trials have failed to demonstrate a beneficial effect of n-3 fatty acids on cardiovascular outcomes, which may be due to the growing use of statins since the mid-1990s. The aim of the present study was to assess whether statins modify the effects of n-3 fatty acids on major adverse cardiovascular events in patients with a history of myocardial infarction (MI). METHODS AND RESULTS: Patients who participated in the Alpha Omega Trial were divided into consistent statin users (n = 3740) and consistent statin non-users (n = 413). In these two groups of patients, the effects of an additional daily amount of 400 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA), 2 g alpha-linolenic acid (ALA), or both on major cardiovascular events were evaluated. Multivariable Cox's proportional hazard models were used to calculate adjusted hazard rate ratios (HR(adj)). Among the statin users 495 (13%) and among the statin non-users 62 (15%) developed a major cardiovascular event. In statin users, an additional amount of n-3 fatty acids did not reduce cardiovascular events [HR(adj) 1.02; 95% confidence interval (CI): 0.80, 1.31; P = 0.88]. In statin non-users, however, only 9% of those who received EPA-DHA plus ALA experienced an event compared with 18% in the placebo group (HR(adj) 0.46; 95% CI: 0.21, 1.01; P= 0.051). CONCLUSION: In patients with a history of MI who are not treated with statins, low-dose supplementation with n-3 fatty acids may reduce major cardiovascular events. This study suggests that statin treatment modifies the effects of n-3 fatty acids on the incidence of major cardiovascular events. PMID- 22301767 TI - The efficacy of NMDA receptor antagonists for preventing remifentanil-induced increase in postoperative pain and analgesic requirement: a meta-analysis. AB - BACKGROUND: Meta-analysis was performed to evaluate the preventive effects of N methyl-D-aspartate (NMDA) receptor antagonists on remifentanil-induced increase in postoperative pain and analgesic requirement in patients. METHODS: Pubmed, EMBase, Springer and the Cochrane Controlled Trials Register were searched to identify all randomized controlled trials (RCTs) published to November 2010 which investigated the preventive effects of NMDA receptor antagonists on remifentanil induced postoperative hyperalgesia and/or tolerance. The studies listed at the end of these articles as reference were also searched. Two authors independently assessed the quality of each study met the inclusion criteria and extracted data. Then Meta-analysis was perfomed using RevMan 5.0 software. The outcomes analyzed were the postoperative analgesic consumption, pain intensity scores, time to first analgesic request, and the incidence of adverse effects. RESULTS: A total of 623 patients (223 in the ketamine group, 87 in the magnesium group and 313 in the control group) from 14 prospective RCTs were included in the Meta-analysis. Administration of NMDA receptor antagonists reduced the pain scores at 4 hr after operation (P<0.05), and the standardized mean differences (SMD) was -0.21 (95% confidence interval was -0.41 to -0.01). There were no significant differences in postoperative analgesic consumption, pain scores at other time points, time to first analgesic request and the incidence of adverse effects (P>0.05). Further subgroup analyses based on the type of intervention showed that the results were almost the same. CONCLUSION: These data do not support the use of NMDA receptor antagonists, ketamine and magnesium sulfate to prevent the development of remifentanil-induced postoperative hyperalgesia and tolerance. PMID- 22301768 TI - Synthesis, characterization, and catalytic properties of new half-sandwich zirconium(IV) complexes. AB - A number of new half-sandwich zirconium(IV) complexes bearing N,N-dimethylaniline amido ligands with the general formula Cp*ZrCl(2)[ortho (RNCH(2))(Me(2)N)C(6)H(4)] [R = 2,6-Me(2)C(6)H(3) (1), 2,6-(i)Pr(2)C(6)H(3) (2), (i)Pr (3), (t)Bu (4)] were synthesized by the reaction of Cp*ZrCl(3) with the corresponding ortho-(Me(2)N)C(6)H(4)CH(2)NRLi. All new zirconium complexes were characterized by (1)H and (13)C NMR, elemental analyses and single crystal X-ray diffraction analysis. The molecular structural analysis reveals that the NMe(2) group does not coordinate to the zirconium atom in all cases. Complexes 1-4 all have a pseudo-tetrahedral coordination environment in their solid state structures and adopt a three-legged piano stool geometry for the zirconium atoms with the amide N atom and the two Cl atoms being the three legs and the Cp* ring being the seat. Variable-temperature (1)H NMR experiments for all complexes 1-4 were performed to investigate the possible intramolecular interaction between the N atom in the NMe(2) group and the central zirconium atom in solution. Upon activation with Al(i)Bu(3) and Ph(3)CB(C(6)F(5))(4), complexes 1-4 all exhibit moderate to good catalytic activity for ethylene polymerization and copolymerization with 1-hexene, producing linear polyethylene or poly(ethylene-co 1-hexene) with moderate molecular weight and reasonable 1-hexene incorporation. PMID- 22301769 TI - Detection of interstitial lung disease in systemic sclerosis through partitioning of lung transfer for carbon monoxide. AB - BACKGROUND: Interstitial lung disease (ILD) is a leading cause of death in systemic sclerosis (SSc). Sensitivities and specificities of the current pulmonary function tests (PFTs) for the detection of ILD in SSc are poor. OBJECTIVE: To determine whether diffusion capacity of the lungs for carbon monoxide (DLCO) partitioned into membrane conductance for CO (DmCO) and alveolar capillary blood volume (Vcap) could provide more sensitive clues to ILD than current PFTs. METHODS: DmCO and Vcap were determined in 35 consecutive SSc patients in whom a cardiac and/or pulmonary vascular abnormality had been rejected according to the recommended screening algorithm. ILD was diagnosed with high-resolution computed tomography. RESULTS: Among 35 patients [6 men; median age (first-third quartile) 61.9 years (49.5-67.7)], 22 had no ILD and 13 did. Total lung capacity (TLC), vital capacity and DLCO [percentage of predicted value (%pred)] were lower in patients with ILD [86 (82-103) vs. 106 (98-112), p = 0.01, 96 (88-112) vs. 114 (104-121), p = 0.04, and 67 (59-81) vs. 80 (71-94), p = 0.02, respectively]. DmCO (%pred) and the ratio of DmCO to Vcap were much lower in patients with ILD [54 (48-72) vs. 83 (66-92), p < 0.001, and 0.22 (0.21-0.27) vs. 0.40 (0.35-0.53), p < 0.0001, respectively]. According to receiver operating characteristic analysis, the DmCO:Vcap ratio displayed higher sensitivity and specificity than TLC, vital capacity and DLCO in identifying ILD in our study group (p < 0.01). CONCLUSIONS: These results suggest that the partitioning of DLCO might be of interest for identifying ILD in SSc patients. PMID- 22301770 TI - Ionic liquids in confined geometries. AB - Over recent years the Surface Force Apparatus (SFA) has been used to carry out model experiments revealing structural and dynamic properties of ionic liquids confined to thin films. Understanding characteristics such as confinement induced ion layering and lubrication is of primary importance to many applications of ionic liquids, from energy devices to nanoparticle dispersion. This Perspective surveys and compares SFA results from several laboratories as well as simulations and other model experiments. A coherent picture is beginning to emerge of ionic liquids as nano-structured in pores and thin films, and possessing complex dynamic properties. The article covers structure, dynamics, and colloidal forces in confined ionic liquids; ionic liquids are revealed as a class of liquids with unique and useful confinement properties and pertinent future directions of research are highlighted. PMID- 22301771 TI - Sequential self-assembly for construction of Pt(II)-bridged [3]rotaxanes on gold nanoparticles. AB - An effective self-assembly route for construction of Pt(II)-bridged [3]rotaxane functionalized gold nanoparticles was developed through a stepwise introduction of Pt(II) coordination and gold-thiol binding in turn. The sequential self assembly process can be quantitatively controlled and directly monitored by the naked eye. PMID- 22301772 TI - Mixtures of cationic copolymers and oppositely charged surfactants: effect of polymer charge density and ionic strength on the adsorption behavior at the silica-aqueous interface. AB - This study addresses polymer-surfactant interactions at solid-liquid interfaces and how these can be manipulated by modulating the association between ionic surfactant and oppositely charged polymer, with a particular focus on electrostatic interactions. For this purpose, the interaction of a series of cationic copolymers of vinylpyrrolidone and quaternized vinylimidazol with sodium dodecyl sulfate (SDS) at the silica-aqueous interface was followed by in situ ellipsometry. To reveal the nature of the interaction, we performed measurements for different copolyion charge densities, in the absence and presence of added salt. The path-dependence of the interaction was studied by comparing the adsorption under two different conditions, adsorption from premixed solutions and sequential addition of surfactant to the polymer solution, but the same end state. The reversibility of the adsorption process was studied by following the effect of dilution on the adsorbed layer. All copolyions adsorbed to both silica and hydrophobized silica, revealing the importance of both hydrophobic and electrostatic attractive interactions. On both types of surface, an increase in adsorbed amount was found on lowering the fraction of charged units. An increased ionic strength gave an increased adsorbed amount in all cases, but especially on hydrophobic surfaces. The adsorbed amount on silica from mixtures of the copolyions with SDS peaked at an SDS concentration corresponding closely to the concentration of cationic charges of the different polyions. Around the region of charge equivalence, there was also a phase separation in the bulk. At higher concentrations of SDS, a redissolution in the bulk, and a decrease in adsorbed amount, occurred as a result of excess SDS binding to the complexes. For the most highly charged polyions, we observed a decrease in adsorbed amount, and a shift in the adsorption maxima to lower SDS concentrations, with increasing ionic strength. PMID- 22301773 TI - Coriandrum sativum L. protects human keratinocytes from oxidative stress by regulating oxidative defense systems. AB - BACKGROUND: Oxidative radicals are major environmental causes of human skin damage. Oxidative defense factors, including nuclear factor erythroid-derived 2 related factor 2 (Nrf2), are centrally involved in repairing skin cells or protecting them from oxidative damage. Coriandrum sativum L. (coriander; CS) is a commonly consumed food and a traditional phytomedicine in Asia and Europe. In this study, we examined the protective effects of a standardized CS leaf extract against oxidative stress in human HaCaT keratinocytes. METHODS AND RESULTS: CS significantly and dose-dependently protected cells against reduced cell viability caused by H2O2-induced damage, as assessed using the 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide assay. Other assays demonstrated that CS protected HaCaT cells by increasing the levels of glutathione and activities of oxidative defense enzymes, such as superoxide dismutase and catalase. Moreover, it increased the expression of activated Nrf2, which plays a crucial role in protecting skin cells against oxidative stress. CONCLUSION: These results suggest that CS protects human keratinocytes from H2O2-induced oxidative stress through antioxidant effects. PMID- 22301774 TI - 2-Aminopyrimidine as a novel scaffold for biofilm modulation. AB - An efficient synthetic route to a series of substituted 2-aminopyrimidine (2-AP) derivatives has been developed. Subsequent biofilm screening has allowed comparison between the biological activity of these new derivatives and that of the 2-aminoimidazole class of anti-biofilm compounds. Several derivatives displayed the ability to modulate bacterial biofilm formation, exhibiting greater activity against Gram-positive strains than Gram-negative strains. Additionally some 2-aminopyrmidines were able to suppress MRSA resistance to conventional antibiotics. PMID- 22301775 TI - Expression of high-affinity human antibody fragments in bacteria. AB - Here we describe protocols for the expression of human antibody fragments in Escherichia coli. Antigen-specific clones are identified by soluble fragment ELISA and concentrated by periplasmic preparation. They are then further purified by affinity chromatography. This article provides an overview of expression and purification strategies for human antibody fragments, as well as detailed protocols for the identification of high-affinity binders and for affinity maturation. PMID- 22301776 TI - A pipeline for the generation of shRNA transgenic mice. AB - RNA interference (RNAi) is an extremely effective tool for studying gene function in almost all metazoan and eukaryotic model systems. RNAi in mice, through the expression of short hairpin RNAs (shRNAs), offers something not easily achieved with traditional genetic approaches-inducible and reversible gene silencing. However, technical variability associated with the production of shRNA transgenic strains has so far limited their widespread use. Here we describe a pipeline for the generation of miR30-based shRNA transgenic mice that enables efficient and consistent targeting of doxycycline-regulated, fluorescence-linked shRNAs to the Col1a1 locus. Notably, the protocol details crucial steps in the design and testing of miR30-based shRNAs to maximize the potential for developing effective transgenic strains. In all, this 14-week procedure provides a fast and cost effective way for any laboratory to investigate gene function in vivo in the mouse. PMID- 22301777 TI - Improved biocytin labeling and neuronal 3D reconstruction. AB - In this report, we describe a reliable protocol for biocytin labeling of neuronal tissue and diaminobenzidine (DAB)-based processing of brain slices. We describe how to embed tissues in different media and how to subsequently histochemically label the tissues for light or electron microscopic examination. We provide a detailed dehydration and embedding protocol using Eukitt that avoids the common problem of tissue distortion and therefore prevents fading of cytoarchitectural features (in particular, lamination) of brain tissue; as a result, additional labeling methods (such as cytochrome oxidase staining) become unnecessary. In addition, we provide correction factors for tissue shrinkage in all spatial dimensions so that a realistic neuronal morphology can be obtained from slice preparations. Such corrections were hitherto difficult to calculate because embedding in viscous media resulted in highly nonlinear tissue deformation. Fixation, immunocytochemistry and embedding procedures for light microscopy (LM) can be completed within 42-48 h. Subsequent reconstructions and morphological analyses take an additional 24 h or more. PMID- 22301778 TI - Single-mRNA counting using fluorescent in situ hybridization in budding yeast. AB - Fluorescent in situ hybridization (FISH) allows the quantification of single mRNAs in budding yeast using fluorescently labeled single-stranded DNA probes, a wide-field epifluorescence microscope and a spot-detection algorithm. Fixed yeast cells are attached to coverslips and hybridized with a mixture of FISH probes, each conjugated to several fluorescent dyes. Images of cells are acquired in 3D and maximally projected for single-molecule analysis. Diffraction-limited labeled mRNAs are observed as bright fluorescent spots and can be quantified using a spot detection algorithm. FISH preserves the spatial distribution of cellular RNA distribution within the cell and the stochastic fluctuations in individual cells that can lead to phenotypic differences within a clonal population. This information, however, is lost if the RNA content is measured on a population of cells by using reverse transcriptase PCR, microarrays or high-throughput sequencing. The FISH procedure and image acquisition described here can be completed in 3 d. PMID- 22301779 TI - Contact mechanics for layered materials with randomly rough surfaces. AB - The contact mechanics model of Persson is applied to layered materials. We calculate the M function, which relates the surface stress to the surface displacement, for a layered material, where the top layer (thickness d) has different elastic properties than the semi-infinite solid below. Numerical results for the contact area as a function of the magnification are presented for several cases. As an application, we calculate the fluid leak rate for laminated rubber seals. PMID- 22301780 TI - Minireview: Inflammation: an instigator of more aggressive estrogen receptor (ER) positive breast cancers. AB - Approximately 75% of breast tumors express the estrogen receptor (ER), and women with these tumors will receive endocrine therapy. Unfortunately, up to 50% of these patients will fail ER-targeted therapies due to either de novo or acquired resistance. ER-positive tumors can be classified based on gene expression profiles into Luminal A- and Luminal B-intrinsic subtypes, with distinctly different responses to endocrine therapy and overall patient outcome. However, the underlying biology causing this tumor heterogeneity has yet to become clear. This review will explore the role of inflammation as a risk factor in breast cancer as well as a player in the development of more aggressive, therapy resistant ER-positive breast cancers. First, breast cancer risk factors, such as obesity and mammary gland involution after pregnancy, which can foster an inflammatory microenvironment within the breast, will be described. Second, inflammatory components of the tumor microenvironment, including tumor-associated macrophages and proinflammatory cytokines, which can act on nearby breast cancer cells and modulate tumor phenotype, will be explored. Finally, activation of the nuclear factor kappaB (NF-kappaB) pathway and its cross talk with ER in the regulation of key genes in the promotion of more aggressive breast cancers will be reviewed. From these multiple lines of evidence, we propose that inflammation may promote more aggressive ER-positive tumors and that combination therapy targeting both inflammation and estrogen production or actions could benefit a significant portion of women whose ER-positive breast tumors fail to respond to endocrine therapy. PMID- 22301781 TI - Identification of microRNAs that mediate thyroid cell growth induced by TSH. AB - TSH is a major regulator of thyroid cell growth and endocrine function. It is known that cAMP and phosphatidylinositol 3-kinase (PI3K) are responsible for mediating the action of TSH. Activation of these signals results in the induction of a series of transcription factors and cell cycle regulating proteins, which induce cell proliferation. In addition to such canonical transcriptional regulation, it was recently shown that microRNA (miRNA or miR) constitutes another key mechanism for the regulation of gene expression. However, whether TSH action is mediated by miRNA in the thyroid is unknown. In this study, we have performed miRNA microarray analysis and demonstrated that TSH significantly decreases expression of 47 miRNA in thyroid cells. Among these, we have shown, using their specific agonists, that overexpression of miR-16 and miR-195 suppressed cell cycle progression and DNA synthesis that was induced by TSH. In silico analysis predicted that Mapk8, Ccne1, and Cdc6, the expression of which was up-regulated by TSH, are potential target genes for these miRNA, and overexpression of miR-16 and miR-195 suppressed expression of these target genes. The decrease of miR-16 and miR-195 expression by TSH was reproduced by forskolin and N(6),2'-O-dibutyryladenosine cAMP and reversed by the protein kinase A inhibitor H89 and the PI3K inhibitor LY294002. These results suggest that TSH activates cAMP/protein kinase A and PI3K cascades to decrease miR-16 and miR-195, which induce Mapk8, Ccne1, and Cdc6 to activate cell proliferation. PMID- 22301782 TI - CtBP1 interacts with Ikaros and modulates pituitary tumor cell survival and response to hypoxia. AB - C-terminal binding protein (CtBP) is a transcriptional corepressor that plays an important role in mammalian development and tumorigenesis. We demonstrate that CtBP is expressed in adenohypophyseal cells and is expressed at high levels in human corticotroph, somatotroph, and lactotroph pituitary adenomas. CtBP interacts with Ikaros isoforms in GH4 and AtT20 pituitary tumor cells. Ikaros and CtBP1 expression is coordinately induced by hypoxia, and this response is abrogated by CtBP1 deficiency. Forced reduction of CtBP1 leads to reduced cell growth, up-regulation of Sprouty 2, and down-regulation of ectonucleotide pyrophosphatase phosphodiesterase 2 (Enpp2). Consistent with diminished Enpp2 activity, CtBP1-deficient pituitary cells are more susceptible to hypoxia-induced apoptosis, which is rescued by Enpp2-derived lysophosphatidic acid treatment. These results identify putative oncogenic properties of CtBP1 and provide new insights into the overlapping functions of two members of the chromatin remodeling network in the response to hypoxic pituitary tumor cell drive. PMID- 22301783 TI - The nuclear orphan receptor Nur77 is a lipotoxicity sensor regulating glucose induced insulin secretion in pancreatic beta-cells. AB - The NR4A orphan nuclear receptors Nur77, Nurr1, and Nor1 exert multiple cellular and metabolic functions. These transcriptional regulators are activated in response to extracellular stresses, including lipotoxic fatty acids (FA) and proinflammatory cytokines. The contribution of NR4As to beta-cell pathophysiology is, however, unknown. We have therefore examined the role of NR4As as downstream contributors to FA-induced beta-cell dysfunctions. Human pancreatic islets and insulinoma beta-cells were used to determine transcriptional programs elicited by NR4A, which were compared to those triggered by palmitate treatment. Functional studies evaluated the consequence of an increased NR4A expression on insulin biosynthesis and secretion and cell viability in insulinoma beta-cells. FA and cytokine treatment increased NR4A expression in pancreatic beta-cells, with Nur77 being most highly inducible in murine beta-cells. Nur77, Nurr1, or Nor1 modulated common and distinct clusters of genes involved notably in cation homeostasis and insulin gene transcription. By altering zinc homeostasis, insulin gene transcription, and secretion, Nur77 was found to be a major transcriptional mediator of part of FA-induced beta-cell dysfunctions. The repressive role of Nur77 in insulin gene regulation was tracked down to protein-protein interaction with FoxO1, a pivotal integrator of the insulin gene regulatory network. The present study identifies a member of the NR4A nuclear receptor subclass, Nur77/NR4A1, as a modulator of pancreatic beta-cell biology. Together with its previously documented role in liver and muscle, its role in beta-cells establishes Nur77 as an important integrator of glucose metabolism. PMID- 22301784 TI - V1b and CRHR1 receptor heterodimerization mediates synergistic biological actions of vasopressin and CRH. AB - Vasopressin (AVP) and CRH synergistically regulate adrenocorticotropin and insulin release at the level of the pituitary and pancreas, respectively. Here, we first extended these AVP and CRH coregulation processes to the adrenal medulla. We demonstrate that costimulation of chromaffin cells by AVP and CRH simultaneously induces a catecholamine secretion exceeding the one induced by each hormone alone, thus demonstrating a net potentiation. To further elucidate the molecular mechanisms underlying this synergism, we coexpressed human V1b and CRH receptor (CRHR)1 receptor in HEK293 cells. In this heterologous system, AVP also potentiated CRH-stimulated cAMP accumulation in a dose-dependent and saturable manner. This effect was only partially mimicked by phorbol ester or inhibited by a phospholipase C inhibitor respectively. This finding suggests the existence of an new molecular mechanism, independent from second messenger cross talk. Similarly, CRH potentiated the AVP-induced inositol phosphates production. Using bioluminescence resonance energy transfer, coimmunoprecipitation, and receptor rescue experiments, we demonstrate that V1b and CRHR1 receptors assemble as heterodimers. Moreover, new pharmacological properties emerged upon receptors cotransfection. Taken together, these data strongly suggest that direct molecular interactions between V1b and CRHR1 receptors play an important role in mediating the synergistic interactions between these two receptors. PMID- 22301785 TI - Mice deficient in dual oxidase maturation factors are severely hypothyroid. AB - Dual oxidases (DUOX1 and DUOX2) are evolutionary conserved reduced nicotinamide adenine dinucleotide phosphate oxidases responsible for regulated hydrogen peroxide (H(2)O(2)) release of epithelial cells. Specific maturation factors (DUOXA1 and DUOXA2) are required for targeting of functional DUOX enzymes to the cell surface. Mutations in the single-copy Duox and Duoxa genes of invertebrates cause developmental defects with reduced survival, whereas knockdown in later life impairs intestinal epithelial immune homeostasis. In humans, mutations in both DUOX2 and DUOXA2 can cause congenital hypothyroidism with partial iodide organification defects compatible with a role of DUOX2-generated H(2)O(2) in driving thyroid peroxidase activity. The DUOX1/DUOXA1 system may account for residual iodide organification in patients with loss of DUOX2, but its physiological function is less clear. To provide a murine model recapitulating complete DUOX deficiency, we simultaneously targeted both Duoxa genes by homologous recombination. Knockout of Duoxa genes (Duoxa(-/-) mice) led to a maturation defect of DUOX proteins lacking Golgi processing of N-glycans and to loss of H(2)O(2) release from thyroid tissue. Postnatally, Duoxa(-/-) mice developed severe goitreous congenital hypothyroidism with undetectable serum T4 and maximally disinhibited TSH levels. Heterozygous mice had normal thyroid function parameters. (125)I uptake and discharge studies and probing of iodinated TG epitopes corroborated the iodide organification defect in Duoxa(-/-) mice. Duoxa(-/-) mice on continuous T4 replacement from P6 showed normal growth without an overt phenotype. Our results confirm in vivo the requirement of DUOXA for functional expression of DUOX-based reduced nicotinamide adenine dinucleotide phosphate oxidases and the role of DUOX isoenzymes as sole source of hormonogenic H(2)O(2). PMID- 22301786 TI - Molecular Mechanism of TNFalpha-Induced Down-Regulation of SHBG Expression. AB - The reason why obesity (a chronic low-grade inflammatory disease) is associated with low levels of sex hormone-binding globulin (SHBG) remains to be elucidated. The present study provides evidence that TNFalpha (a proinflammatory cytokine increased in obesity) reduces SHBG production by human HepG2 hepatoblastoma cells. Although the human SHBG promoter contains one nuclear factor-kappaB (NF kappaB) binding site, the human SHBG promoter activity did not change after TNFalpha treatment or transfection with either small interfering RNA against p65 or a p65 expression vector in luciferase reporter gene assays. The effect of TNFalpha on human SHBG expression was indirect, and it was mediated by NF-kappaB through the down-regulation of hepatocyte nuclear factor (HNF)-4A: a key SHBG transcriptional regulator. Furthermore, the HNF-4A proximal promoter contains three putative NF-kappaB binding sites. The HNF-4A promoter activity was decreased by the treatment with TNFalpha or the transfection of a p65 expression vector, and it was increased by the treatment with small interfering RNA against NF-kappaB in luciferase reporter gene assays. Finally, the TNFalpha treatment promotes the NF-kappaB binding to the HNF-4A promoter in chromatin immunoprecipitation assays. We conclude that sustained exposition to elevated levels of TNFalpha decreases SHBG production by reducing hepatic HNF-4alpha levels via NF-kappaB activation in HepG2 cells. PMID- 22301787 TI - DARPP-32 is required for MAPK/ERK signaling in thyroid cells. AB - Modulation of MAPK signaling duration by cAMP defines its physiological output by driving cells toward proliferation or differentiation. Understanding how the kinetics of MAPK signaling are integrated with other cellular signals is a key issue in development and cancer. Here we show that dopamine and cAMP-regulated neuronal phosphoprotein, 32 kDa (DARPP-32), a protein required for thyroid cell differentiation, determines whether MAPK/ERK activation is sustained or transient. Serum, a stimulus that activates MAPK signaling and does not independently increase DARPP-32 levels results in transient activation of the MAPK pathway. By contrast, TSH + (IGF-I) activate MAPK signaling but also independently increase DARPP-32 levels. Our results are consistent with a model in which maintenance of DARPP-32 expression by TSH + IGF-I leads to sustained MAPK signaling. Moreover, the sensitivity of MAPK/ERK signaling in thyroid cells is lost when de novo DARPP-32 expression is blocked by small interfering RNA. Because both DARPP-32 levels and function as inhibitor of protein phosphatase 1, a key inhibitor of MAPK kinase activity, are governed by cAMP/protein kinase A, the results may explain why in thyroid cells cAMP signaling downstream from TSH controls the duration of MAPK pathway activity. Thus, fine-tuning of DARPP-32 levels leads to changes in the kinetics or sensitivity of MAPK/ERK signaling. Given the implications of MAPK signaling in thyroid cancer and the loss of DARPP 32 in tumor and transformed thyroid cells, DARPP-32 may represent a key therapeutic target. PMID- 22301788 TI - Hybridization in nanostructured DNA monolayers probed by AFM: theory versus experiment. AB - Nanografted monolayers (NAMs) of DNA show novel physico-chemical properties that make them ideally suited for advanced biosensing applications. In comparison with alternative solid-phase techniques for diagnostic DNA detection, NAMs have the advantage of combining a small size with a high homogeneity of the DNA surface coverage. These two properties favour the extreme miniaturization and ultrasensitivity in high-throughput biosensing devices. The systematic use of NAMs for quantitative DNA (and protein) detection has so far suffered from the lack of a control on key fabrication parameters, such as the ss- or ds-DNA surface coverage. Here we report on a combined experimental-computational study that allows us to estimate the surface density of the grafted DNA by analyzing the sample mechanical response, that is the DNA patch height vs. applied tip load curves. It is shown that the same analysis scheme can be used to detect the occurrence of hybridization with complementary strands in solution and estimate its efficiency. Thanks to these quantitative relationships it is possible to use a single AFM-based setup to: (i) fabricate a DNA NAM, (ii) control the DNA surface coverage, and (iii) characterize its level of hybridization helping the design of NAMs with pre-determined fabrication parameters. PMID- 22301790 TI - A simple method for imaging Arabidopsis leaves using perfluorodecalin as an infiltrative imaging medium. AB - The problem of acquiring high-resolution images deep into biological samples is widely acknowledged. In air-filled tissue such as the spongy mesophyll of plant leaves or vertebrate lungs further difficulties arise from multiple transitions in refractive index between cellular components, between cells and airspaces and between the biological tissue and the rest of the optical system. Moreover, refractive index mismatches lead to attenuation of fluorophore excitation and signal emission in fluorescence microscopy. We describe here the application of the perfluorocarbon, perfluorodecalin (PFD), as an infiltrative imaging medium which optically improves laser scanning confocal microscopy (LSCM) sample imaging at depth, without resorting to damaging increases in laser power and has minimal physiological impact. We describe the protocol for use of PFD with Arabidopsis thaliana leaf tissue, which is optically complex as a result of its structure (Figure 1). PFD has a number of attributes that make it suitable for this use. The refractive index of PFD (1.313) is comparable with that of water (1.333) and is closer to that of cytosol (approx. 1.4) than air (1.000). In addition, PFD is readily available, non-fluorescent and is non-toxic. The low surface tension of PFD (19 dynes cm-1) is lower than that of water (72 dynes cm-1) and also below the limit (25-30 dyne cm-1) for stomatal penetration, which allows it to flood the spongy mesophyll airspaces without the application of a potentially destructive vacuum or surfactant. Finally and crucially, PFD has a great capacity for dissolving CO2 and O2, which allows gas exchange to be maintained in the flooded tissue, thus minimizing the physiological impact on the sample. These properties have been used in various applications which include partial liquid breathing and lung inflation, surgery, artificial blood, oxygenation of growth media, and studies of ice crystal formation in plants. Currently, it is common to mount tissue in water or aqueous buffer for live confocal imaging. We consider that the use of PFD as a mounting medium represents an improvement on existing practice and allows the simple preparation of live whole leaf samples for imaging. PMID- 22301791 TI - Design considerations for electrostatic microvalves with applications in poly(dimethylsiloxane)-based microfluidics. AB - Microvalves are critical in the operation of integrated microfluidic chips for a wide range of applications. In this paper, we present an analytical model to guide the design of electrostatic microvalves that can be integrated into microfluidic chips using standard fabrication processes and can reliably operate at low actuation potentials (<250 V). Based on the analytical model, we identify design guidelines and operational considerations for elastomeric electrostatic microvalves and formulate strategies to minimize their actuation potentials, while maintaining the feasibility of fabrication and integration. We specifically explore the application of the model to design microfluidic microvalves fabricated in poly(dimethylsiloxane), using only soft-lithographic techniques. We discuss the electrostatic actuation in terms of several microscale phenomena, including squeeze-film damping and adhesion-driven microvalve collapse. The actuation potentials predicted by the model are in good agreement with experimental data obtained with a microfabricated array of electrostatic microvalves actuated in air and oil. The model can also be extended to the design of peristaltic pumps for microfluidics and to the prediction of actuation potentials of microvalves in viscous liquid environments. Additionally, due to the compact ancillaries required to generate low potentials, these electrostatic microvalves can potentially be used in portable microfluidic chips. PMID- 22301792 TI - Proportion of parents agreeing to delay fetal karyotyping until the third trimester of pregnancy in cases with an indication. AB - OBJECTIVE: To assess the extent to which couples who could benefit from fetal karyotyping during the first or second trimester would agree to delay the examination until the third trimester. METHODS: In this prospective monocentric study, the same physician suggested to some couples to delay fetal karyotyping until the third trimester. RESULTS: 458 couples participated in this study. 230 couples (230/458 = 50.2%) refused to delay the examination until the third trimester of pregnancy (group 1). For these patients, four chromosomal abnormalities led to the termination of pregnancy. Fifty-six couples (56/458 = 12.2%) who initially agreed to delay the fetal karyotyping later changed their minds (group 2). 104 couples (104/458 = 22.7%) agreed to delay the examination (group 3). For these patients, one trisomy 21 was diagnosed and led to the subsequent termination of the pregnancy at 33 weeks of amenorrhea. Sixty-eight couples (68/458 = 14.8%) refused any form of invasive prenatal diagnosis (group 4). There was no difference in the rate of preterm premature rupture of membranes, pregnancy term, premature birth rate and birth weight between the four groups. CONCLUSIONS: Our study reports that about a quarter of couples did indeed agree to delay fetal karyotype assessment until the third trimester of pregnancy. PMID- 22301793 TI - Flavivirus infection induces indoleamine 2,3-dioxygenase in human monocyte derived macrophages via tumor necrosis factor and NF-kappaB. AB - Infection with West Nile virus (WNV) via a mosquito bite results in local viral replication in the skin, followed by viremia. Thus, tissue macrophages are ideally located to prevent the dissemination of WNV throughout the host. The current study shows that WNV infection of human monocyte-derived macrophages (MDM) results in increased WNV mRNA, protein, and infectious virions at 24 h p.i. with a decline in titer after 48 h. Concomitant with viral control was the robust induction of indoleamine 2,3-dioxygenase (IDO) and resultant metabolism of L tryptophan (L-Trp) to kynurenine. In WNV-exposed cultures, IDO protein was induced primarily in noninfected versus viral-infected MDM. Whereas WNV infection increased the production of IFN-alpha, IFN-beta, and TNF, only antibody neutralization of TNF attenuated IDO expression and activity. WNV infection also activated NF-kappaB, and inhibition of this pathway with BMS-345541 abrogated IDO induction. Similar results were also obtained with MDM infected with the related flavivirus, Japanese encephalitis virus. Whereas IDO-mediated L-Trp metabolism can exhibit antiviral properties, inhibition of IDO activity in MDM with L-1-MT or the addition of excess L-Trp did not affect viral control. However, culturing MDM in L-Trp-deficient medium or overexpression of IDO in cells prior to infection significantly attenuated WNV replication, which was reversed by adding excess L-Trp. Together, these data support that although IDO is not required by MDM for the clearance of established viral infection, the spread of flavivirus infection is limited by IDO expressed in uninfected, neighboring cells. PMID- 22301794 TI - Platelet-activating factor receptor plays a role in the pathogenesis of graft versus-host disease by regulating leukocyte recruitment, tissue injury, and lethality. AB - PAF is a potent lipid mediator involved in several manifestations of acute inflammation, including leukocyte influx, leukocyte interaction with endothelium, and production of inflammatory cytokines. The present study evaluated the relevance of PAFR for the pathogenesis of acute GVHD using a model of adoptive transfer of splenocytes from WT or PAFR(-/-) C57BL/6J to B6D2F1 mice. Mice, which received PAFR(-/-) splenocytes or treatment with the PAFR antagonist, showed reduced clinical signs of disease and no mortality. In GVHD mice receiving PAFR( /-) splenocytes, there was deceased bacterial translocation and tissue injury. Furthermore, production of proinflammatory cytokines and chemokines (TNF-alpha, IFN-gamma, CCL2, CCL3, and CCL5) and accumulation of CD8(+) cells in intestine and liver were reduced in mice transplanted with the PAFR(-/-) splenocyte. Mechanistically, an absence or pharmacological blockade of PAFR was associated with decreased rolling and adhesion of leukocytes to the mesenteric microcirculation, as assessed by intravital microscopy. Despite decreased GVHD, there was maintained GVL activity when PAFR(-/-) leukocytes were transferred into WT mice. In conclusion, PAFR on donor leukocytes plays a critical role in GVHD by mediating leukocyte influx and cytokine production in target tissues. PAFR antagonist may potentially be useful in the treatment of GVHD in bone marrow transplanted patients. PMID- 22301795 TI - The interplay of metal and supporting ligand in labile coordination to pincer complexes of Ag(I). AB - The bis(imino)pyridine scaffold provides support for the synthesis and characterization of unique Ag(I) pincer complexes [{ArN=CPh}(2)(NPh)]Ag(+)(OTf)( ) (Ar = 2,5-(t)Bu(2)C(6)H(3)3; 2,6-(i)Pr(2)C(6)H(3) 4). The bonding interactions between the cation-anion and between the bis(imino)pyridine ligand and the Ag centre are presented. Coordination of pyridine, toluene, 2-butyne and cyclooctene to the Ag centre led to the isolation and crystallographic characterization of labile transient adduct species. Bonding analysis of the adducts revealed conventional ligand-Ag coordination and important unconventional electron donation from the ligand to a pi*-orbital of the bis(imino)pyridine group. PMID- 22301796 TI - Linear pitting and splinter haemorrhages are more commonly seen in the nails of patients with established psoriasis in comparison to psoriatic arthritis. AB - BACKGROUND: Recently the role of several ligament and tendon insertions around the nail matrix and nail plate have been identified as possible contributory factors that explain the higher prevalence of nail involvement in psoriatic arthritis (PsA). The purpose of this study was to determine whether such anatomical factors might also be associated with different patterns of nail involvement in skin psoriasis and PsA. METHODS: A total of 173 patients were recruited: 121 PsA cases and 52 psoriasis cases. All patients had a standardised assessment of the nails for lesions including pitting, splinter haemorrhages and onycholysis. RESULTS: The overall modified Nail Psoriasis Severity Index scores did not differ between the two groups (psoriasis mean 8.5, SD 7.1; PsA mean 8.3, SD 9.4). In the nail matrix, linear pitting appeared to be more common in skin psoriasis (OR 0.27, 95% CI 0.18-0.41). There were no significant differences in the distribution of nail plate abnormalities other than splinter haemorrhages which were more commonly seen in psoriasis cases (OR 0.23, 95% CI 0.14-0.39). CONCLUSION: The pattern of nail disease in psoriasis and PsA differed with respect to the frequency of linear pitting and splinter haemorrhages, with both features occurring more often in psoriasis. PMID- 22301797 TI - Surface ferromagnetic p-type ZnO nanowires through charge transfer doping. AB - We report first-principles theoretical investigation of p-type charge transfer doping of zinc oxide (ZnO) nanowires by molecular adsorption. We find that spontaneous dissociative adsorption of fluorine molecules introduces half emptying of otherwise fully filled oxygen-derived surface states. The resulting surface Fermi level is so close to the valence band maximum of the ZnO nanowire that the nanowire undergoes significant p-type charge transfer doping. Those half filled surface states are fully spin-polarized and lead to surface ferromagnetism that is stable at room temperature. We also analyze the kinetic control regime of the surface transfer doping and find that it may result in nonequilibrium steady states. The present results suggest that postgrowth engineering of surface states has high potential in manipulating ZnO nanostructures useful for both electronics and spintronics. PMID- 22301799 TI - Comparison of the antiseptic efficacy of tissue-tolerable plasma and an octenidine hydrochloride-based wound antiseptic on human skin. AB - Colonization and infection of wounds represent a major reason for the impairment of tissue repair. Recently, it has been reported that tissue-tolerable plasma (TTP) is highly efficient in the reduction of the bacterial load of the skin. In the present study, the antiseptic efficacy of TTP was compared to that of octenidine hydrochloride with 2-phenoxyethanol. Both antiseptic methods proved to be highly efficient. Cutaneous treatment of the skin with octenidine hydrochloride and 2-phenoxyethanol leads to a 99% elimination of the bacteria, and 74% elimination is achieved by TTP treatment. Technical challenges with an early prototype TTP device could be held responsible for the slightly reduced antiseptic properties of TTP, compared to a standard antiseptic solution, since the manual treatment of the skin surface with a small beam of the TTP device might have led to an incomplete coverage of the treated area. PMID- 22301798 TI - The secret ally: immunostimulation by anticancer drugs. AB - It has recently become clear that the tumour microenvironment, and in particular the immune system, has a crucial role in modulating tumour progression and response to therapy. Indicators of an ongoing immune response, such as the composition of the intratumoural immune infiltrate, as well as polymorphisms in genes encoding immune modulators, have been correlated with therapeutic outcome. Moreover, several anticancer agents--including classical chemotherapeutics and targeted compounds--stimulate tumour-specific immune responses either by inducing the immunogenic death of tumour cells or by engaging immune effector mechanisms. Here, we discuss the molecular and cellular circuitries whereby cytotoxic agents can activate the immune system against cancer, and their therapeutic implications. PMID- 22301800 TI - Elevated levels of the steroidogenic factor 1 are associated with over-expression of CYP19 in an oestrogen-producing testicular Leydig cell tumour. AB - BACKGROUND AND OBJECTIVES: Testicular Leydig cell tumours (LCTs) are rare, steroid-secreting tumours. Elevated levels of aromatase (CYP19 or CYP19A1) mRNA have been previously described in LCTs; however, little is known about the mechanism(s) causing CYP19 over-expression. We report an LCT in a 29-year-old male with elevated plasma oestradiol caused by enhanced CYP19 transcription. DESIGN AND METHODS: First, we measured the intra-tumour expression of CYP19 and determined the use of CYP19 promoters by qPCR. Secondly, we explored CYP19 and promoter II (PII) for gene amplifications and activating mutations in PII by sequencing. Thirdly, we analysed intra-tumour expression of steroidogenic factor 1 (SF-1 (NR5A1)), liver receptor homologue-1 (LRH-1 (NR5A2)) and cyclooxygenase-2 (COX2 (PTGS2)). Finally, we analysed SF-1 for promoter mutations and gene amplifications. RESULTS: Similar to what has been recorded in normal Leydig cells, we first found the bulk of tumour CYP19 transcripts to be PII derived, excluding promoter shift as a cause of enhanced transcription. Secondly, we excluded CYP19 and PII gene amplifications, and activating mutations in PII, as causes of elevated CYP19 mRNA. We found SF-1 mRNA to be up-regulated in the tumour, while LRH-1 and COX2 were down-regulated. The finding of elevated SF-1 levels in the tumour was confirmed by immunohistochemistry. The elevated level of SF-1 was not due to promoter mutations or amplifications of the SF-1 gene. CONCLUSIONS: Our results strongly suggest that the elevated levels of SF-1 have induced PII-regulated CYP19 transcription in this tumour. These findings are of relevance to the understanding of CYP19 up-regulation in general, which may occur in several tissues, including breast cancer. PMID- 22301801 TI - A simple and efficient fluorescent sensor for histidine. AB - A simple coordination complex terpyridine-CuCl(2) is found to be an efficient fluorescent sensor for histidine in aqueous solution with up to 1004 fold fluorescence enhancement. PMID- 22301802 TI - Forced homodimerization of the c-Fos leucine zipper in designed bHLHZ-like hybrid proteins MaxbHLH-Fos and ArntbHLH-Fos. AB - Although the c-Fos leucine zipper (LZ) does not form a homodimer in its native basic region/leucine zipper (bZIP) structure, we found that it is capable of homodimerization and promoting protein folding in engineered basic region/helix loop-helix/leucine zipper (bHLHZ) hybrid proteins MaxbHLH-Fos and ArntbHLH-Fos, in which the bHLH subdomains of Max and Arnt are fused to the c-Fos LZ. By using the in vivo yeast one-hybrid system and in vitro circular dichroism and quantitative fluorescence anisotropy, we demonstrated that attachment of the c Fos LZ to the otherwise unstructured MaxbHLH resulted in a hybrid bHLHZ-like protein now competent for homodimerization and DNA binding at the cognate E-box site, CACGTG. In ArntbHLH-Fos, the c-Fos LZ promoted proper folding of the HLH structure, although unlike MaxbHLH, ArntbHLH alone is capable of homodimerization and DNA binding. In addition, by comparing the E-box binding and secondary structures of MaxbHLH-Fos and two derivatives containing targeted mutations in the c-Fos LZ, we found that cooperative communication exists between the bHLH and LZ: proper folding of the four-helix bundle in the HLH region could be induced by the c-Fos LZ, and the HLH dimerization region could force homodimerization of the c-Fos LZ. These results demonstrate that although intrinsically unfavorable, the c-Fos LZ can homodimerize, demonstrating that the same c-Fos LZ element can yield orthogonal differences in structure and/or DNA-binding function within different transcription factor families, including the bZIP and bHLHZ. PMID- 22301803 TI - Dental fluorosis and its association with the use of fluoridated toothpaste among middle school students of Delhi. AB - INTRODUCTION: Fluorosis can manifest as dental fluorosis (seen mostly in secondary dentition), skeletal fluorosis, and systemic fluorosis. Groundwater with high fluoride concentrations, diet rich in fish and tea, indoor air pollution, and use of fluoride toothpastes may contribute considerably to total exposure. OBJECTIVE: To assess the prevalence of dental fluorosis and associated factors particularly fluoridated toothpastes, among middle school children of a resettlement colony in Delhi. MATERIALS AND METHODS: This survey was conducted among the middle school students (VI th -VIII th ) studying in three government schools of Sangam Vihar, South Delhi. Students were examined for dental fluorosis by experts. A pre-structured questionnaire was used to obtain data regarding age, source of drinking water, toothpaste used, etc. Height, weight, and hemoglobin were recorded. Two repeat visits were made. Out of 432 students enrolled in these schools, 413 students were examined. STATISTICS: Descriptive and chi-square statistics were used. RESULTS: Dental fluorosis was prevalent in 121 (29.3%) study subjects. It was significantly more in children of age 13 years or above, in those who used fluoridated toothpaste for dental cleaning (P=0.033) and in anemic children (P<0.001). However, there was no significant association of disease with gender (P=0.02), source of drinking water (P=0.417), and with BMI (P=0.826). CONCLUSION: As dental fluorosis is very common (in about one-fourth) among the middle school children, in this resettlement colony of Delhi, various control measures e.g. discouraging the fluoridated toothpastes, educating parents about fluorosis, de-fluoridation of water in the high risk areas, etc may help to tackle this situation. PMID- 22301804 TI - Childhood morbidity, household practices and health care seeking for sick children in a tribal district of Maharashtra, India. AB - OBJECTIVES: To find out the magnitude of childhood morbidities, health care seeking behavior and explore the status of 'some desired practices' at household level during episodes of illness in two tribal blocks of Chandrapur district. MATERIALS AND METHODS: The present explanatory mixed-method design of quantitative (survey) and qualitative (focus group discussions, FGDs )methods was undertaken in nine Primary health centers of Warora and Bhadrawati blocks in Chandrapur district. The information of 2,700 under-five children on morbidity, health care seeking behavior and some desired practices at household level was collected by paying home visits and using pre-designed and pre-tested questionnaire. The data was entered and analyzed by using SPSS 12.0.1 and C sample program of epi_info (version 6.04d) software package. The conventional content analysis of FGD data was undertaken. RESULTS: The prevalence of morbidities was high among newborns and children. About 1,811 (67%) children had at least one of the morbidities. Private health care providers and village level faith healers were preferred for seeking treatment of newborn danger sings and childhood morbidities. The status of some desired household practices such as frequent feeding and giving extra fluid to drink during episodes of illness was poor. CONCLUSIONS: In conclusion, considering high prevalence of child morbidities and poor status of some desired household practices of caregivers at household level for sick children, household and community IMNCI strategy needs to be implemented to promote child health and nutrition. Apart from this, health care delivery at village level should be strengthened. PMID- 22301805 TI - Assessment of DNA nucleo base oxidation and antioxidant defense in postmenopausal women under hormone replacement therapy. AB - BACKGROUND AND OBJECTIVE: The aim of the present study was to evaluate oxidative stress by investing oxidatively damaged DNA AS Formamidopyrimidine DNA glycosylase (Fpg) -sensitive sites, glutathione peroxidase (GPx), superoxide dismutase (SOD) activities reduced glutathione (GSH) level and nitrite level as satble end product of in women receiving hormone replacement therapy (HRT). MATERIALS AND METHODS: 127 healthy postmenopausal women receiving HRT and 25 healthy control postmenopausal women were included in this study. Women receiving HRT, comprised surgical menopausal women who underwent surgery for benign conditions and received conjugated equine estrogen, 0.625 mg/day for 1 year (group 1), 5 years (group 2) and more than 10 years (group 3), spontaneous postmenopausal women received conjugated equine estrogen, 0.625 (Premarin) mg/day and medroxyprogesterone acetate, 2.5 mg/day (Premelle) for 1 year (group 4), 5 years (group 5) and more than 5 years (group 6).We investigated in the present study the effects of HRT on nitrite level and GSH level, activities of SOD and GPx and oxidative damage to DNA by comet assays by measuring levels of Fpg sensitive sites. RESULTS: Although no significant differences were found in the SOD activities, in total group receiving HRT, increased DNA oxidation (P<0.001) together with an increased GPx activity (P<0.001) and nitrite level (P<0.001) as well as a decreased GSH level (P < 0.05) as compared with controls were observed. CONCLUSION: Estrogen alone or oestrogen in combination with progesterone and duration of use did not significantly alter the results. We evaluated that caused oxidative stress by investigating oxidative DNA damage as Fp-sensitive sites and GSH.NO levels in women receiving HRT. PMID- 22301806 TI - Computed tomographic pulmonary angiography: utility in acute pulmonary embolism in providing additional information and making alternative clinical diagnosis. AB - OBJECTIVE: To evaluate the role of computed tomographic (CT) pulmonary angiography (CT-PA) in detecting additional information that may help in making an alternative clinical diagnosis in patients referred to CT for a suspected acute pulmonary embolism (PE). MATERIALS AND METHODS: 50 patients (34 males, 16 females) in the age group of 18-72 years (mean 42.3 years), having high clinical suspicion of PE, underwent CTPA over a 2 year period. Chest x-ray, arterial blood gas (ABG) analysis, echocardiography were done in all patients. All patients underwent at least one other imaging examination besides CTPA: ventilation perfusion scan, Doppler ultrasound or compression ultrasound (for DVT). All patients were followed for 3 months after completion of the diagnostic work up at baseline. The final diagnosis was achieved by a combination of clinical, imaging, and laboratory analysis, after adequate imaging, laboratory tests, and follow up. RESULT: CTPA helped correctly identify 29 of 30 patients with PE. In the remaining 20 patients (with no evidence of PE), CT-PA provided additional information (that suggested or confirmed alternate clinical diagnosis) in 15 patients (75%): pleural effusion (n=8), mediastinal or hilar lymphadenopathy (6), pneumonia/airspace consolidation (5), atelectasis/collapse (2), aspergilloma (1), malignancy (1), and others (2). CONCLUSION: CT-PA is highly specific and sensitive for diagnosis of PE. In addition, in a majority of patients who do not have PE, it also provides important ancillary additional information and helps in making an alternative clinical diagnosis. PMID- 22301807 TI - Nephrogenic systemic fibrosis following acute kidney injury and exposure to gadolinium. AB - Nephrogenic systemic fibrosis (NSF) is a scleroderma-like systemic fibrosing condition of unknown etiology described in patients with renal insufficiency. Gadolinium exposure has been strongly associated with the development of NSF though the mechanism of such injury is not known. There are only few reported cases of NSF in the setting of acute renal failure and fewer reported cases where skin lesions developed after kidney function had returned to normal. We report a case of NSF in a young Hispanic woman with lupus nephritis but normal creatinine, who received gadolinium during a brief episode of prerenal acute kidney injury not requiring dialysis, secondary to sepsis. PMID- 22301808 TI - Adrenal sarcomatoid carcinoma: a rare case depicted on multi-detector row computed tomography. AB - Primary adrenal sarcomatoid carcinoma is rare malignant tumor with the characteristics of carcinoma and sarcoma. To date, only one case of primary sarcomatoid carcinoma in the adrenal gland was reported. We present here computed tomography appearance and pathological features of the case with primary adrenal sarcomatoid carcinoma confirmed by pathology. In addition, a brief review of the relevant literature is presented. PMID- 22301809 TI - Application of autologous bone marrow stem cells in giant axonal neuropathy. AB - Giant axonal neuropathy is a rare disorder of autosomal recessive inheritance, morphologically characterized by accumulation of neurofilaments in enlargements of preterminal regions of central and peripheral axons. We present a 7-year-old girl with thick and tightly curled lackluster hair suffering from giant axonal neuropathy. The diagnosis was confirmed on the brain MRI which showed white matter abnormalities in the anterior and posterior periventricular regions as well as the cerebellar white matter. In view of the same, the patient was given intrathecal autologous bone marrow-derived stem cell therapy as part of the neuroregenerative rehabilitation therapy protocol. The patient showed functional improvements in her disability after receiving the therapy. A detailed case report is presented here with. PMID- 22301810 TI - Acute renal failure following electrocution. PMID- 22301811 TI - Efficient HgTe colloidal quantum dot-sensitized near-infrared photovoltaic cells. AB - We have demonstrated the successful fabrication of multiple-layer colloidal quantum dot (CQD)-sensitized near-infrared (NIR) photovoltaic (PV) cells using the solution processable HgTe CQDs and poly-3-(hexylthiophene) (P3HT) as hole conducting polymer. The cells showed a 3.6 fold enhancement in power conversion efficiency under NIR light illumination by the post-ethanedithiol chemical treatment. The performance enhancement was mainly ascribed to the improved interfacial contact between HgTe CQDs by elimination of oleic acid as capping ligand on the surface of HgTe CQDs. In addition, the HgTe CQD-sensitized PV cells could effectively detect weak NIR light and process over 1 kHz level signals. PMID- 22301812 TI - Relationship between memory performance and beta-amyloid deposition at different stages of Alzheimer's disease. AB - BACKGROUND: Postmortem studies have suggested that beta-amyloid (Abeta) deposition was only weakly related to the degree of cognitive impairment in Alzheimer's disease (AD). The development of Abeta ligands for in vivo PET imaging has greatly facilitated the assessment of this question. OBJECTIVE: The objective of the present study was to provide an overview of our current knowledge regarding the relationship between Abeta deposition and episodic memory deficits in nondemented elderly and in patients with mild cognitive impairment or AD. METHODS: Information was obtained both from studies comparing memory performance in individuals with high Pittsburgh compound B (PiB) and those with low PiB and from studies performing correlation analyses between memory performance and PiB retention considered as a continuous variable. RESULTS: Previous studies assessing the relationship between memory and global neocortical PiB reported conflicting findings, and overall suggest that this link is weak, probably indirect, and detectable only in early stages. Assessing the relationship with regional instead of global neocortical PiB, we found a specific relationship between episodic memory deficits and neocortical temporal PiB, independent from hippocampal atrophy, in the predementia stage of the disease. CONCLUSION: There is a relationship between regional Abeta deposition and episodic memory deficits in the presymptomatic stage of AD. PMID- 22301813 TI - Assaying the kinase activity of LRRK2 in vitro. AB - Leucine Rich Repeat Kinase 2 (LRRK2) is a 2527 amino acid member of the ROCO family of proteins, possessing a complex, multidomain structure including a GTPase domain (termed ROC, for Ras of Complex proteins) and a kinase domain. The discovery in 2004 of mutations in LRRK2 that cause Parkinson's disease (PD) resulted in LRRK2 being the focus of a huge volume of research into its normal function and how the protein goes awry in the disease state. Initial investigations into the function of LRRK2 focused on its enzymatic activities. Although a clear picture has yet to emerge of a consistent alteration in these due to mutations, data from a number of groups has highlighted the importance of the kinase activity of LRRK2 in cell death linked to mutations. Recent publications have reported inhibitors targeting the kinase activity of LRRK2, providing a key experimental tool. In light of these data, it is likely that the enzymatic properties of LRRK2 afford us an important window into the biology of this protein, although whether they are potential drug targets for Parkinson's is open to debate. A number of different approaches have been used to assay the kinase activity of LRRK2. Initially, assays were carried out using epitope tagged protein overexpressed in mammalian cell lines and immunoprecipitated, with the assays carried out using this protein immobilised on agarose beads. Subsequently, purified recombinant fragments of LRRK2 in solution have also been used, for example a GST tagged fragment purified from insect cells containing residues 970 to 2527 of LRRK2. Recently, Daniels et al. reported the isolation of full length LRRK2 in solution from human embryonic kidney cells, however this protein is not widely available. In contrast, the GST fusion truncated form of LRRK2 is commercially available (from Invitrogen, see table 1 for details), and provides a convenient tool for demonstrating an assay for LRRK2 kinase activity. Several different outputs for LRRK2 kinase activity have been reported. Autophosphorylation of LRRK2 itself, phosphorylation of Myelin Basic Protein (MBP) as a generic kinase substrate and phosphorylation of an artificial substrate--dubbed LRRKtide, based upon phosphorylation of threonine 558 in Moesin -have all been used, as have a series of putative physiological substrates including alpha-synuclein, Moesin and 4-EBP. The status of these proteins as substrates for LRRK2 remains unclear, and as such the protocol described below will focus on using MBP as a generic substrate, noting the utility of this system to assay LRRK2 kinase activity directed against a range of potential substrates. PMID- 22301814 TI - Green tea extract alleviates arsenic-induced biochemical toxicity and lipid peroxidation in rats. AB - The present work was undertaken to evaluate the protective effect of an aqueous extract of green tea (GT, Camellia sinensis) leaves against arsenic (NaAsO2) induced biochemical toxicity and lipid peroxidation production in experimental rats. The treatment with arsenic exhibited a significant increase in some serum hepatic and renal biochemical parameters (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, albumin, bilirubin, cholesterol, urea and creatinine). But the co-administration of GT has increased the level of plasmatic concentration of biochemical parameters. Exposure of rats to arsenic caused also a significant increase in liver, kidney and testicular thiobarbituric acid reactive substances compared to control. However, the co administration of GT was effective in reducing its level. To conclude, our data suggest that arsenic exposure enhanced an oxidative stress by disturbing the tissue antioxidant defense system, but the GT co-administration alleviates the toxicity induced by arsenic exposure. PMID- 22301815 TI - Changes in carbohydrate metabolism, oxidative stress and loss of cortisol secretion in adrenocortica l cells of Oreochromis niloticus exposed in vitro to endosulfan. AB - The effects of endosulfan, an organochlorine pesticide regularly used in Niger Delta ecological zone, were examined and also its effects on various biochemical parameters in the serum of Oreochromis niloticus, a dominant fish species in Nigeria. One hundred and fifty juveniles of O. niloticus were used for the toxicity study. Lethal concentration of 50% mortality of sample (LC50) was determined using semi-static method. From the result of the LC50 determination, lower concentrations of endosulfan were prepared for sublethal test. Five fish per test concentration in three replicates were exposed to varying concentrations of endosulfan. Glucose level and the enzyme activities were measured spectrophotometrically at the end of 28 days of exposure. Glucose levels and glutathione-S-transferase activities were significantly (p < 0.05) higher than the control and the concentrations increased with increasing concentration of the toxicant and exposure duration. Cortisol secretion was significantly (p = 0.05) lower in the treated fish than the control. These findings indicated that endosulfan altered all the investigated parameters, which is an indication of their suitability as markers for fish and other aquatic organism toxicity study. PMID- 22301816 TI - Effect of Thiovit(R) Jet on the structure of thoracic microtrichia/trichomes in Drosophila melanogaster. AB - Widely used fungicides and pesticides are known to have profound effect on several nontarget organisms, which is a cause of concern. The present study aims to demonstrate the effect of a fungicide, Thiovit((r)) Jet on the structure of epidermal microtrichia (trichome) of the dorsal thorax in Drosophila melanogaster. External morphology and structural variations of thoracic appendages have been extensively studied using scanning electron microscope from flies treated with different concentrations of Thiovit Jet (20, 30, 40 or 200 MUg/ml). Similar to the effect of other fungicides like captan and captafol which are reported to produce somatic mutations in the same organism, the present study successfully demonstrates variation in the trichome/microtrichia structure of the dorsal thorax of D. melanogaster. Structural variations were observed to be associated with different concentrations of Thiovit Jet (30, 40 and 200 MUg/ml), but the maximum notable change was found with 40 MUg/ml treatment. The gross abnormality in the trichome structure may be due to mutation in proteins associated with normal cuticular deposition. PMID- 22301817 TI - Cadmium concentrations in shrimp (Penaeus semisulcatus and Penaeus monodon) caught from the coastal areas in Southern Iran. AB - This study was undertaken to determine the concentration of cadmium in two shrimp species, namely, Penaeus semisulcatus and Penaeus monodon caught from the coastal areas in southern Iran. Cadmium concentration was determined by graphite furnace atomic absorption spectrophotometry in 91 shrimp samples after nitric acid/perchloric acid digestion. Accuracy of the analysis was checked by various methods including the use of reference material. The mean +/- SD of cadmium concentrations in shrimp samples were 0.128 +/- 0.144 (MUg/g). The cadmium concentrations ranged from 0.010 to 0.96 MUg/g of the muscle tissues of shrimp. Higher cadmium concentration in shrimp samples was found in summer (significant p < 0.05). The results show that the mean concentration of cadmium in shrimp is lower than the maximum allowed levels according to International standards, although the concentration of cadmium in only one sample was more than the amount recommended by Food and Agriculture Organization. Therefore, no risk to the consumer arises from the cadmium contents of the shrimp caught in these areas. PMID- 22301818 TI - Screening of immunomodulatory activity of total and protein extracts of some Moroccan medicinal plants. AB - Herbal and traditional medicines are being widely used in practice in many countries for their benefits of treating different ailments. A large number of plants in Morocco were used in folk medicine to treat immune-related disorders. The objective of this study is to evaluate the immunomodulatory activity of protein extracts (PEs) of 14 Moroccan medicinal plants. This activity was tested on the proliferation of immune cells. The prepared total and PEs of the plant samples were tested using MTT (3-(4,5-dimethylthiazol-2yl)-2,5 diphenyltetrazolium bromide) assay on the splenocytes with or without stimulation by concanavalin-A (Con-A), a mitogenic agent used as positive control. The results of this study indicated different activity spectra. Three groups of activities were observed. The first group represented by Citrullus colocynthis, Urtica dioica, Elettaria cardamomum, Capparis spinosa and Piper cubeba showed a significant immunosuppressive activity. The second group that showed a significant immunostimulatory activity was represented by Aristolochia longa, Datura stramonium, Marrubium vulgare, Sinapis nigra, Delphynium staphysagria, Lepidium sativum, Ammi visnaga and Tetraclinis articulata. The rest of the plant extracts did not alter the proliferation induced by Con-A. This result was more important for the PE than for the total extract. In conclusion, this study revealed an interesting immunomodulating action of certain PEs, which could explain their traditional use. The results of this study may also have implications in therapeutic treatment of infections, such as prophylactic and adjuvant with cancer chemotherapy. PMID- 22301819 TI - Proposed remedies for some developmental disorders. AB - Developmental disorders (DDs) are important leading cause of disability in developed countries and also in the United States. DDs are a group of individual conditions that result from abnormal nervous system development and cause altered function. They can begin at any time from prenatal to 22 years of age and the disability usually presents itself throughout a person's life time. Down syndrome, autism, neural tube defects, schizophrenia, cretinism, and attention deficit hyperactivity disorder are among the most common DDs that currently plague numerous countries and have varying incidence rates. Their occurrence may be partially attributable to the lack of certain dietary nutrients. Notably, essential vitamins, minerals, and omega-3 fatty acids are often deficient in the general population of America and developed countries and are exceptionally deficient in patients suffering from mental disorders. Typically, most of these disorders are treated with prescription drugs, but many of these drugs cause unwanted side effects. Therefore, psychiatrists recommend alternative or complementary nutritional remedies to overcome the adverse effects of those drugs. Studies have shown that daily supplements of vital nutrients, such as that contain amino acids, often effectively reduce symptoms of the patients, because they are converted into neurotransmitters that alleviate depression and other mental disorders. The aim of this article is to discuss the role of dietary imbalances in the incidence of DD and to emphasize which dietary supplements can aid in the treatment of the above-mentioned DD. PMID- 22301820 TI - A simple clinical model to estimate the probability of Marfan syndrome. AB - BACKGROUND: Marfan syndrome is a heritable connective tissue disease. Definitive diagnosis is complex, and requires sequencing of a large gene, FBN1. AIM: We aimed to develop a simple model to estimate the pre-test probability of Marfan syndrome. DESIGN: Prospective cross-sectional study. METHODS: We applied diagnostic standards for definitive diagnosis or exclusion of Marfan syndrome in 329 consecutive persons. In 208 persons with random assignment to our derivation group, we performed multivariate logistic regression to assess 14 clinical variables for inclusion in a prediction model with derivation of score points from the estimated coefficients. We created cut-offs to classify low, moderate and high probability of Marfan syndrome. For validation, we applied the model to the remaining 121 persons. RESULTS: We identified seven variables for inclusion in the final model, where we assigned four score points to ectopia lentis, two points to a family history of Marfan syndrome, and one point to previous thoracic aortic surgery, to pectus excavatum, to a wrist and thumb sign, to previous pneumothorax, and to skin striae. In the derivation group 12, 42 and 92% of persons with low (<=1 point), moderate (>1-3.5 points) or high pre-test probability (>3.5 points) had Marfan syndrome, compared to 12, 57 and 91%, respectively, in the validation group. Positive likelihood ratios were 13.96 and 8.54 in the high probability group of the derivation and validation group, respectively. CONCLUSION: A simple prediction model provides evidence for Marfan syndrome. This model can be used to identify patients who require definitive diagnostic work-up. PMID- 22301821 TI - Practical global outreach: translating UK clinical experience. PMID- 22301822 TI - Lyme disease in a British referral clinic. AB - BACKGROUND: Concerns about over-diagnosis and inappropriate management of Lyme disease (LD) are well documented in North America and supported by clinical data. There are few parallel data on the situation in the UK. AIM: To describe the patterns of referral, investigation, diagnosis and treatment of patients with suspected LD referred to an infectious disease unit in Liverpool, UK. Previous management by National Health Service (NHS) and non-NHS practitioners was reviewed. DESIGN: Descriptive study conducted by retrospective casenotes review. METHODS: Retrospective casenotes review of adults referred with possible LD to an infectious disease unit in Liverpool, UK, over 5 years (2006-2010). RESULTS: Of 115 patients, 27 (23%) were diagnosed with LD, 38 (33%) with chronic fatigue syndrome (CFS) and 13 (11%) with other medical conditions. No specific diagnosis could be made in 38 (33%). At least 53 unnecessary antibiotic courses had been given by non-NHS practitioners; 21 unnecessary courses had been prescribed by NHS practitioners. Among 38 patients, 17 (45%) with CFS had been misdiagnosed as having LD by non-NHS practitioners. CONCLUSION: A minority of referred patients had LD, while a third had CFS. LD is over-diagnosed by non-specialists, reflecting the complexities of clinical and/or laboratory diagnosis. Patients with CFS were susceptible to misdiagnosis in non-NHS settings, reinforcing concerns about missed opportunities for appropriate treatment for this group and about the use of inappropriate diagnostic modalities and anti-microbials in non NHS settings. PMID- 22301823 TI - Characteristics of late onset neutropenia in rheumatologic patients treated with rituximab: a case review analysis from a single center. AB - BACKGROUND: Late onset neutropenia (LON) secondary to rituximab has been reported as an adverse event in the treatment of hematological malignancies but reports on autoimmune diseases are scarce. AIM: To review the characteristics of LON in rheumatologic patients from a single center. DESIGN: Retrospective case record study. METHODS: Clinical and laboratory data since the introduction of rituximab in our clinic in 2006 were collected and analyzed retrospectively. LON was defined as an absolute neutrophil count <1.0 * 10(9)/l occurring 4 weeks after the last rituximab infusion. RESULTS: LON was identified in eight patients (6% of all patients receiving rituximab). All patients had complicated and refractory disease and had been treated with a median of 4.5 different immunosuppressive drugs prior to rituximab. LON appeared after a median interval of 23 weeks with recovery of LON after a median of 6.5 days. Four patients had concomitant infection at the onset of neutropenia, when six patients had both low immunoglobulin M and immunoglobulin G. Six patients were rechallenged with rituximab without recurrence of LON. CONCLUSION: The characteristics of LON after rituximab treatment in patients with autoimmune disease are comparable with experiences from hematological malignancies. LON seems to precede B-cell recovery implying a perturbation of the granulocyte homeostasis. LON with its rapid recovery does not seem to increase the risk for serious infection in contrast to the sustained hypogammaglobulinemia that may follow rituximab. The risk of LON recurrence after rechallenge is low. PMID- 22301825 TI - Preparation of a nitrate-coordinated copper(II) complex of 2-(pyrazol-3-yl)-6 (pyrazolate)pyridine as an efficient catalyst for methyl methacrylate polymerization. AB - Treatment of [CuCl(2)(bppyH(2))] (1, bppyH(2) = 2,6-di(1H-pyrazol-3-yl)pyridine) with 2 equiv. of AgNO(3) in DMF gave rise to a binuclear Cu(II) complex [Cu(2)(bppyH)(2)(NO(3))(2)] (bppyH = 2-(pyrazol-3-yl)-6-(pyrazolate)pyridine) (2). Complex 2 was characterized by elemental analysis, IR and single crystal X ray diffraction. Complex 2 has a dimeric structure in which the two Cu(ii) centers are bridged by a couple of the in situ-generated bppyH(-) anions. Each Cu(II) center is further coordinated by one O atom of a NO(3)(-) anion and three N atoms of one bppyH(-) anion. Complex 2 exhibited a higher catalytic activity in the polymerization of methyl methacrylate (MMA) than the precursor complex 1. Even though the ratio of catalyst to MMA was raised up to 1 : 1500, the PDI for 2 (reaction time was fixed at 4 h) is 1.63 and the conversion is up to 72%. The effects of solvent, reaction temperature and the ratio of MMA to catalyst were also investigated. PMID- 22301826 TI - Evaluation of the German guideline for chronic pruritus: results of a retrospective study on 385 patients. AB - OBJECTIVES: The first guideline for the treatment of chronic pruritus was published in 2005. The recommendations are based mainly on case series studies or expert opinions. This retrospective study aimed at analyzing the outcome of treatment according to the German guidelines in a representative cohort of patients. METHODS: 385 consecutive patients with chronic pruritus were evaluated for therapeutic outcome. RESULTS: 268/385 patients (69.6%) reported an antipruritic effect while 117/385 (30.4%) showed no response. Three therapeutic steps were undertaken by 40.3% of the responding patients. CONCLUSIONS: Treating pruritus patients according to the German guideline achieved a high response rate. A prolonged treatment period with multiple therapeutic steps was needed by a high number of patients due to the lack of specific antipruritic substances. Given that multiple therapy steps produce a high disease and economic burden, novel target-specific therapies are eligible. PMID- 22301827 TI - Urinary 8-oxoguanine as a predictor of survival in patients undergoing radiotherapy. AB - BACKGROUND: Because of the importance to identify prognostic indicator for radiotherapy, herein we decided to check whether the parameters which describe oxidative stress/DNA damage may be used as a marker of the therapy. The aim of this work was to investigate whether fractionated radiotherapy of patients with cancer (n = 99) is responsible for oxidative DNA damage on the level of the whole organism and whether the biomarkers of the damage such as 8-oxo-7,8-dihydro-2' deoxyguanosine (8-oxo-dG) and its modified base 8-oxo-7,8-dihydroguanine (8-oxo Gua) in urine and DNA may be used as a predictor of radiotherapy success. METHODS: All the aforementioned modifications were analyzed using techniques which involve high-performance liquid chromatography/electrochemical detection (HPLC/EC) or HPLC/gas chromatography-mass spectroscopy (GC-MS). RESULTS: Of all analyzed parameters only patients with significantly elevated urinary excretion of the 8-oxo-Gua with concomitant unchanged level of 8-oxo-dG in leukocytes DNA in the samples collected 24 hours after the first fraction in comparison to the initial level have significantly increased survival time (60 months after the treatment, survival of 50% of the patients who fulfill the above mentioned criteria, in comparison with 10% of the patients who did not). CONCLUSIONS: Results of our work suggest that patients with higher urinary 8-oxo-Gua and concomitant stable level of 8-oxo-dG in leukocytes DNA, after 24 hours of the first dose should be regarded as better responder to radiotherapy as being at lower risk of mortality. IMPACT: The above mentioned statement could make it possible to use these parameters as markers to predict the clinical success. PMID- 22301828 TI - The associations of advanced glycation end products and its soluble receptor with pancreatic cancer risk: a case-control study within the prospective EPIC Cohort. AB - BACKGROUND: Advanced glycation end products (AGE) and their receptors (RAGE) have been implicated in cancer development through their proinflammatory capabilities. However, prospective data on their association with cancer of specific sites, including pancreatic cancer, are limited. METHODS: Prediagnostic blood levels of the AGE product Nepsilon-(carboxymethyl)lysine (CML) and the endogenous secreted receptor for AGE (esRAGE) were measured using ELISA in 454 patients with exocrine pancreatic cancer and individually matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC). Pancreatic cancer risk was estimated by calculating ORs with corresponding 95% confidence intervals (CI). RESULTS: Elevated CML levels tended to be associated with a reduction in pancreatic cancer risk [OR = 0.57 (95% CI, 0.32-1.01) comparing highest with lowest quintile), whereas no association was observed for esRAGE (OR = 0.98; 95% CI, 0.62-1.54). Adjustments for body mass index and smoking attenuated the inverse associations of CML with pancreatic cancer risk (OR = 0.78; 95% CI, 0.41 1.49). There was an inverse association between esRAGE and risk of pancreatic cancer for cases that were diagnosed within the first 2 years of follow-up [OR = 0.46 (95% CI, 0.22-0.96) for a doubling in concentration], whereas there was no association among those with a longer follow-up (OR = 1.11; 95% CI, 0.88-1.39; P(interaction) = 0.002). CONCLUSIONS AND IMPACT: Our results do not provide evidence for an association of higher CML or lower esRAGE levels with risk of pancreatic cancer. The role of AGE/RAGE in pancreatic cancer would benefit from further investigations. PMID- 22301829 TI - Kinetics of DNA adduct formation in the oral cavity after drinking alcohol. AB - BACKGROUND: Alcohol consumption is one of the top 10 risks for the worldwide burden of disease and an established cause of head and neck cancer, as well as cancer at other sites. Acetaldehyde, the major metabolite of ethanol, reacts with DNA to produce adducts, which are critical in the carcinogenic process and can serve as biomarkers of exposure and, possibly, of disease risk. Acetaldehyde associated with alcohol consumption is considered "carcinogenic to humans." We have previously developed the technology to quantify acetaldehyde-DNA adducts in human tissues, but there are no studies in the literature defining the formation and removal of acetaldehyde-DNA adducts in people who consumed alcohol. METHODS: We investigated levels of N(2)-ethylidene-dGuo, the major DNA adduct of acetaldehyde, in DNA from human oral cells at several time points after consumption of increasing alcohol doses. Ten healthy nonsmokers were dosed once a week for three weeks. Mouthwash samples were collected before and at several time points after the dose. N(2)-Ethylidene-dGuo was measured as its NaBH(3)CN reduction product N(2)-ethyl-dGuo by liquid chromatography-electrospray-tandem mass spectrometry. RESULTS: N(2)-ethylidene-dGuo levels increased as much as 100 fold from baseline within 4 hours after each dose for all subjects and in a dose responsive manner (P = 0.001). CONCLUSION: These results show an effect of alcohol on oral cell DNA adduct formation, strongly supporting the key role of acetaldehyde in head and neck cancer caused by alcohol drinking. IMPACT: Our results provide some of the first conclusive evidence linking exposure to a lifestyle carcinogen and kinetics of DNA adduct formation in humans. PMID- 22301830 TI - Prevalidation of salivary biomarkers for oral cancer detection. AB - BACKGROUND: Oral cancer is the sixth most common cancer with a 5-year survival rate of approximately 60%. Presently, there are no scientifically credible early detection techniques beyond conventional clinical oral examination. The goal of this study is to validate whether the seven mRNAs and three proteins previously reported as biomarkers are capable of discriminating patients with oral squamous cell carcinomas (OSCC) from healthy subjects in independent cohorts and by a National Cancer Institute (NCI)-Early Detection Research Network (EDRN)-Biomarker Reference Laboratory (BRL). METHODS: Three hundred and ninety-five subjects from five independent cohorts based on case controlled design were investigated by two independent laboratories, University of California, Los Angeles (Los Angeles, CA) discovery laboratory and NCI-EDRN-BRL. RESULTS: Expression of all seven mRNA and three protein markers was increased in OSCC versus controls in all five cohorts. With respect to individual marker performance across the five cohorts, the increase in interleukin (IL)-8 and subcutaneous adipose tissue (SAT) was statistically significant and they remained top performers across different cohorts in terms of sensitivity and specificity. A previously identified multiple marker model showed an area under the receiver operating characteristic (ROC) curve for prediction of OSCC status ranging from 0.74 to 0.86 across the cohorts. CONCLUSIONS: The validation of these biomarkers showed their feasibility in the discrimination of OSCCs from healthy controls. Established assay technologies are robust enough to perform independently. Individual cutoff values for each of these markers and for the combined predictive model need to be further defined in large clinical studies. IMPACT: Salivary proteomic and transcriptomic biomarkers can discriminate oral cancer from control subjects. PMID- 22301831 TI - Screening mammography use among current, former, and never hormone therapy users may not explain recent declines in breast cancer incidence. AB - BACKGROUND: Screening mammography and invasive breast cancer and ductal carcinoma in situ (DCIS) rates recently declined in the United States; screening mammography declines among former hormone therapy (HT) users may be an important contributor. We longitudinally examined women and compared mammography use and cancer rates by HT use [current, former, and never users of estrogen + progestin (EPT) and estrogen only (ET)]. METHODS: We studied 163,490 unique women aged 50 79 years enrolled in Group Health (Washington State) between 1994-2009. Electronic data identified HT dispensing, mammography use and incident breast cancer diagnosis. We calculated age-adjusted screening compliance as a time varying variable (screened-within-the-past-26 months, yes/no). RESULTS: Before 2002, screening compliance differed significantly by HT with current EPT users having the highest rates (83%) followed by former EPT (77%), current ET (77%), former ET (72%), and never users (56%). After 2002, screening was high (~81%) among current and former EPT and ET users and significantly increased among never users (~62%). Invasive breast cancer rates significantly decreased over the whole study period (P(trend) <= 0.05) for all HT users, except EPT current users (P(trend) = 0.68); DCIS rates did not change in any group. CONCLUSIONS: Differential screening mammography rates by HT use do not explain invasive breast cancer incidence declines. Our data suggest discontinuing HT has an immediate effect on breast cancer rates, lending support to the mechanism that cessation leads to tumor regression. IMPACT: Studies examining the influence of a changing exposure in relation to outcomes should account for varying exposures, individuals' characteristics, as well as screening methods and frequency. PMID- 22301832 TI - Genetic variation in peroxisome proliferator-activated receptor gamma, soy, and mammographic density in Singapore Chinese women. AB - BACKGROUND: PPARgamma is a transcription factor important for adipogenesis and adipocyte differentiation. Data from animal studies suggest that PPARgamma may be involved in breast tumorigenesis, but results from epidemiologic studies on the association between PPARgamma variation and breast cancer risk have been mixed. Recent data suggest that soy isoflavones can activate PPARgamma. We investigated the interrelations of soy, PPARgamma, and mammographic density, a biomarker of breast cancer risk in a cross-sectional study of 2,038 women who were members of the population-based Singapore Chinese Health Study Cohort. METHODS: We assessed mammographic density using a computer-assisted method. We used linear regression to examine the association between 26 tagging single-nucleotide polymorphisms (SNP) of PPARgamma and their interaction with soy intake and mammographic density. To correct for multiple testing, we calculated P values adjusted for multiple correlated tests (P(ACT)). RESULTS: Out of the 26 tested SNPs in the PPARgamma, seven SNPs were individually shown to be statistically significantly associated with mammographic density (P(ACT) = 0.008-0.049). A stepwise regression procedure identified that only rs880663 was independently associated with mammographic density which decreased by 1.89% per-minor allele (P(ACT) = 0.008). This association was significantly stronger in high-soy consumers as mammographic density decreased by 3.97% per-minor allele of rs880663 in high-soy consumers (P(ACT) = 0.006; P for interaction with lower soy intake = 0.017). CONCLUSIONS: Our data support that PPARgamma genetic variation may be important in determining mammographic density, particularly in high-soy consumers. IMPACT: Our findings may help to identify molecular targets and lifestyle intervention for future prevention research. PMID- 22301833 TI - Carbohydrate ingestion during exercise: effects on performance, training adaptations and trainability of the gut. AB - Carbohydrate feeding has been shown to enhance endurance performance. During exercise of 2 h or more, the delivery of carbohydrates to the muscle is the crucial step and appears to be limited by intestinal absorption. It is therefore important to identify ways to overcome this limitation and study the positive and negative effects of chronic carbohydrate supplementation. There is evidence that intestinal absorption can, at least partly, be overcome by making use of multiple transportable carbohydrates. Ingestion of these carbohydrates may result in higher intestinal absorption rates and has been shown to lead to higher rates of exogenous carbohydrate oxidation which can result in better endurance performance. It also seems possible to increase the absorptive capacity of the intestine by adapting to a high-carbohydrate diet. Carbohydrate supplementation during exercise has been suggested to reduce training adaptations, but at present there is little or no evidence to support this. Despite the fact that it has long been known that carbohydrate supplementation can enhance endurance performance, there are still many unanswered questions. However, there is potential to develop strategies that enhance the delivery of carbohydrates and thereby improve endurance performance. PMID- 22301834 TI - Altering endogenous carbohydrate availability to support training adaptations. AB - Glycogen was first identified in muscle over a century and a half ago. Even though we have known of its existence and its role in metabolism for a long time, recognition of its ability to directly and indirectly modulate signaling and the adaptation to exercise is far more recent. Acute exercise induces a number of changes within the body (i.e. sympathetic nervous system activation and elevation of plasma free fatty acids) and muscle (increased AMP-activated protein kinase activity and fat metabolism) that may underlie the long- term adaptation to training. These changes are also affected by glycogen depletion. This review discusses the effect of exercise in a glycogen-depleted state on metabolism and signaling and how this affects the adaptation to exercise. Although 'training low' may increase cellular markers associated with training and enhance functions such as fat oxidation at sub- maximal exercise intensities, how this translates to performance is unclear. Further research is warranted to identify situations both in health and athletic performance where training with low glycogen levels may be beneficial. In the meantime, athletes and coaches need to weigh the pros and cons of training with low carbohydrate within a periodized training program. PMID- 22301835 TI - Metabolic regulation of fat use during exercise and in recovery. AB - Fat is an important fuel for exercise but plays a secondary role to carbohydrate (CHO). Increasing fat use during exercise can decrease the reliance on CHO and spare CHO for later in training sessions or competitions that depend on CHO for success. The pathways that metabolize and oxidize fat are activated more slowly than CHO at the onset of exercise and reach a maximum at moderate exercise intensities. As exercise intensity increases to ~75% VO(2max) and beyond, fat metabolism is inhibited: using CHO will increase the amount of energy produced per liter of oxygen consumed. The capacity for fat use during exercise is increased by aerobic training and the dietary combination of little or no CHO intake and high fat intake. Fat oxidation is very dependent on the mitochondrial volume of muscle but other key sites of regulation include release of fat from storage forms and fat transport across plasma and mitochondrial membranes. This chapter examines the control of fat metabolism during moderate and intense exercise with an emphasis on human findings and the adaptations that occur with aerobic training and other acute nutritional manipulations. Recent work using molecular and cellular compartmentalization techniques have advanced the knowledge in this area. PMID- 22301836 TI - Fat adaptation science: low-carbohydrate, high- fat diets to alter fuel utilization and promote training adaptation. AB - The effect of manipulating an individual's habitual diet on skeletal muscle fuel utilization has been of longstanding interest to scientists, and it is now well established that changes in dietary intake that alter the concentration of blood borne substrates and hormones cause substantial perturbations in the macronutrient storage profile of muscle and exert profound effects on rates of substrate oxidation during exercise. Only recently, however, has it become appreciated that nutrient-exercise interventions can modulate many contraction- induced responses in muscle, and that fuel availability per se provides a 'trigger' for adaptation. Consumption of low-carbohydrate, high- fat diets in the face of endurance training alters patterns of fuel utilization and subsequent exercise responses. Human studies show how low-carbohydrate, fat-rich diets interact with specific contractile stimulus to modulate many of the acute responses to exercise, thereby promoting or inhibiting subsequent training adaptation. PMID- 22301837 TI - Dietary protein to support muscle hypertrophy. AB - Intact protein, protein hydrolysates, and free amino acids are popular ingredients in contemporary sports nutrition, and have been suggested to augment post-exercise recovery. Protein and/or amino acid ingestion stimulates skeletal muscle protein synthesis, inhibits protein breakdown and, as such, stimulates muscle protein accretion following resistance and endurance type exercise. This has been suggested to lead to a greater adaptive response to each successive exercise bout, resulting in more effective muscle reconditioning. Despite limited evidence, some basic guidelines can be defined regarding the preferred type, amount, and timing of dietary protein that should be ingested to maximize post exercise muscle protein accretion. Whey protein seems most effective in stimulating muscle protein synthesis during acute post-exercise recovery. This is likely attributable to its rapid digestion and absorption kinetics and specific amino acid composition. Ingestion of approximately 20 g protein during and/or immediately after exercise is sufficient to maximize post-exercise muscle protein synthesis rates. Coingestion of a large amount of carbohydrate or free leucine is not warranted to further augment post- exercise muscle protein synthesis when ample protein is already ingested. Future research should focus on the relevance of the acute anabolic response following exercise to optimize the skeletal muscle adaptive response to exercise training. PMID- 22301838 TI - Effect of protein, dairy components and energy balance in optimizing body composition. AB - Weight loss is achieved through the consumption of a hypoenergetic diet and/or increased energy expenditure through exercise. While weight loss is associated with numerous benefits, the pattern of weight loss in terms of body composition changes is not always studied. In our view, the optimum pattern of weight loss is one in which fat mass is lost and lean mass is preserved. The preservation of lean mass has important consequences due to the role of this tissue in contributing to basal metabolic rate, controlling glycemia, and contributing to lipid oxidation. We also propose that a preservation of lean mass would have important consequences in resisting weight regain after loss. We review dietary practices, including reduced consumption of dietary carbohydrate, consuming higher than recommended dietary protein, with an emphasis on dairy sources, as well as dietary calcium, to accelerate the loss of fat mass during dieting and preserve lean mass. Available evidence suggests that each practice has a highly plausible mechanistic and growing clinical rationale in terms of efficacy in promoting fat mass loss and lean mass retention during a hypoenergetic diet. PMID- 22301839 TI - Effect of cell hydration on metabolism. AB - Prerequisites for cell survival include avoidance of excessive cell volume alterations. Cell membranes are highly permeable to water, which follows osmotic gradients. Thus, cell volume constancy requires osmotic equilibrium across cell membranes. Cells accumulate osmotically active organic substances and compensate their osmolarity by lowering cytosolic Cl(-) concentrations. Following cell shrinkage, regulatory cell volume increase is accomplished by ion uptake (activation of Na(+), K(+), 2Cl(-) cotransport, Na(+)/H(+) exchange in - parallel to Cl(-)/HCO(-)(3) exchange and Na(+) channels), by cellular accumulation of organic osmolytes (e.g. myoinositol, betaine, phosphorylcholine, taurine) as well as by proteolysis leading to generation of amino acids and glycogenolysis generating glucose phosphate. Following cell swelling, cell volume is restored by ion exit (activation of K(+) channels and/ - or anion channels, KCl cotransport, parallel activation of K(+)/H(+) exchange and Cl(-)/HCO(-)(3) exchange), release or degradation of organic osmolytes as well as stimulation of protein synthesis and of glycogen synthesis. The activity of cell volume regulatory mechanisms is modified by hormones, transmitters and drugs, which thus influence protein and glycogen metabolism. Moreover, alterations of cell volume modify generation of oxidants and the sensitivity to oxidative stress. Deranged cell volume regulation significantly contributes to the pathophysiology of several disorders such as liver insufficiency, diabetic ketoacidosis, hypercatabolism, ischemia, and fibrosing disease. PMID- 22301840 TI - Practical nutritional recommendations for the athlete. AB - The aim of training is to achieve optimum performance on the day of competition via three processes or paradigms; training hard to create the required training stimulus, training smart to maximize adaptations to the training stimulus, and training specifically to fine- turn the behaviors or physiology needed for competition strategies. Dietary strategies for competition must target the factors that would otherwise cause fatigue during the event, promoting an enhancement of performance by reducing or delaying the onset of these factors. In some cases, the nutritional strategies needed to achieve these various paradigms are different, and even opposite to each other, so athletes need to periodize their nutrition, just as they periodize their training program. The evolution of new knowledge from sports nutrition research, such as presented in this book, usually starts with a stark concept that must be further refined; to move from individual nutrients to food, from 'one size fits all' to the individual needs and practices of different athletes, and from single issues to an integrated picture of sports nutrition. The translation from science to practice usually requires a large body of follow-up studies as well as experimentation in the field. PMID- 22301841 TI - Nanolaminates: increasing dielectric breakdown strength of composites. AB - Processable, low-cost, high-performance hybrid dielectrics are enablers for a vast array of green technologies, including high-temperature electrical insulation and pulsed power capacitors for all-electric transportation vehicles. Maximizing the dielectric breakdown field (E(BD)), in conjunction with minimization of leakage current, directly impacts system performance because of the field's quadratic relationship with electrostatic energy storage density. On the basis of the extreme internal interfacial area and ultrafine morphology, polymer-inorganic nanocomposites (PNCs) have demonstrated modest increases in E(BD) at very low inorganic loadings, but because of insufficient control of the hierarchal morphology of the blend, have yielded a precipitous decline in E(BD) at intermediate and high inorganic volume fractions. Here in, we demonstrate that E(BD) can be increased up to these intermediate inorganic volume fractions by creating uniform one-dimensional nanocomposites (nanolaminates) rather than blends of spherical inorganic nanoparticles and polymers. Free standing nanolaminates of highly aligned and dispersed montmorillonite in polyvinyl butyral exhibited enhancements in E(BD) up to 30 vol % inorganic (70 wt % organically modified montmorillonite). These relative enhancements extend up to five times the inorganic fraction observed for random nanoparticle dispersions, and are anywhere from two to four times greater than observed at comparable volume fraction of nanoparticles. The breakdown characteristics of this model system suggested a trade-off between increased path tortuosity and polymer deficient structural defects. This implies that an idealized PNC morphology to retard the breakdown cascade perpendicular to the electrodes will occur at intermediate volume fractions and resemble a discotic nematic phase where highly aligned, high-aspect ratio nanometer thick plates are uniformly surrounded by nanoscopic regions of polymer. PMID- 22301842 TI - Alopecia areata during treatment of psoriasis with adalimumab and leflunomide: a case and review of the literature. AB - The pathogenesis of alopecia areata (AA) is not clear, even though it is believed to be an autoimmune mechanism which involves T lymphocytes and cytokines such as tumor necrosis factor alpha. We report the case of a 43-year-old man with psoriasis and psoriatic arthritis who developed AA during his treatment with adalimumab and leflunomide. We perform a review of the literature associating AA with biological therapy and leflunomide. We cannot exclude that the use of these therapies and the development of AA could be coincidental. However, we consider that case reports like ours are essential for clinicians as early alerts if similar observations occur. PMID- 22301843 TI - GENOCOP algorithm and hierarchical grid transformation for image warping of two dimensional gel eletrophoretic maps. AB - Hierarchical grid transformation is a powerful approach to SDS 2DPAGE maps warping. The hierarchy of the warping transformation is able to model both global and local deformations of the gels and the algorithm can be stopped when a certain degree of accuracy in the image alignment is obtained. The numerical optimization of the position of the nodes of the grid that are responsible for the image warping is a multivariate task that can be solved efficiently using Genetic Algorithms. The use of Genetic Algorithms ensures that an optimal position of the nodes can be defined with a low computational cost with respect to other methods. The optimal positions of the nodes of the grid can be successfully used for defining a good warping of the gels. PMID- 22301844 TI - Magnetic-field-induced diameter-selective synthesis of single-walled carbon nanotubes. AB - We report a facile and scalable approach to synthesize single-walled carbon nanotubes (SWNTs) with selected diameter distribution by applying a magnetic field perpendicular to the electric field in the arc plasma region. It is found that this magnetic field-induced diameter-selectivity strategy enables the control of the SWNTs with different diameter distributions in different regions, and the diameter-selective efficiency could be enhanced by modifying the direction of magnetic field. Our results indicate that the motions of the catalysts with different particle sizes, positive carbon ions and electrons are significantly influenced by the magnetic field and electromagnetic force, resulting in the different nucleation and growth processes of SWNTs due to the collective interactions between the magnetic field and arc plasma. This approach would enable a viable route towards the synthesis of SWNTs with desired diameter through the tuning of arc parameters in the arc discharge process. PMID- 22301845 TI - Synthesis, molecular and electronic structure of an incomplete cuboidal Re3S4 cluster with an unusual quadruplet ground state. AB - A Re(IV) cluster complex [Re(3)(MU(3)-S)(MU-S)(3)(dppe)(3)Br(3)](+) with nine cluster skeletal electrons (CSE) and a quadruplet ground state has been prepared by treatment of [Re(3)S(7)Br(6)]Br with 1,2-bis(diphenylphosphino)ethane (dppe) in MeCN. PMID- 22301846 TI - Effects of remote ischemic preconditioning with postconditioning in patients undergoing off-pump coronary artery bypass surgery--randomized controlled trial. AB - BACKGROUND: Myocardial injury is associated with an adverse outcome after off pump coronary artery bypass graft surgery (OPCAB). The authors conducted a randomized controlled trial to evaluate whether remote ischemic preconditioning (RIPC) with remote ischemic postconditioning (RIPostC) reduces myocardial injury in patients undergoing OPCAB. METHODS AND RESULTS: Seventy patients scheduled for OPCAB were randomly assigned to an RIPC+RIPostC group (n=35) or a control group (n=35). In the RIPC+RIPostC group, 4 cycles of 5-min ischemia and 5-min reperfusion were done on a lower limb before anastomoses (RIPC) and after anastomoses (RIPostC). RIPC+RIPostC significantly reduced postoperative serum troponin I levels (P=0.001). The area under the curve for postoperative troponin I was 48.7% lower in the RIPC+RIPostC group (median [interquartile range], 21.3 h.ng-1.ml-1, 16.5-53.1 h.ng-1.ml-1 vs. 41.5 h.ng-1.ml-1, 24.6-90.2 h.ng-1.ml-1, P=0.020). There was no significant difference in creatinine levels and PaO2/F(i)O2 ratios between the 2 groups. CONCLUSIONS: RIPC+RIPostC by lower limb ischemia decreased postoperative myocardial enzyme elevation by almost half postoperatively in patients undergoing OPCAB. PMID- 22301847 TI - Improved prognosis of Takayasu arteritis over the past decade--comprehensive analysis of 106 patients. AB - BACKGROUND: We aimed to describe the recent clinical characteristics of Takayasu arteritis (TA). METHODS AND RESULTS: We enrolled 106 consecutive TA patients and compared the clinical characteristics of patients with TA onset before 1999 and after 2000, patients with onset at age less than 39 years and more than 40 years, patients with monophasic and relapsing-remitting clinical course, and patients with and without human lymphocyte antigen (HLA)-B52 allele. Among the patients with TA onset after 2000, the time from onset to diagnosis had decreased; the frequency of occlusion in aortic arch branches and the complication of moderate or severe aortic regurgitation (AR) had decreased, and the maximum dose of prednisolone and the use of immunosuppressive agents had increased. In patients with onset at age more than 40 years, the complications of coronary artery lesions and hypertension had increased, and the incidence of moderate or severe AR had decreased. In the relapsing-remitting group, the maximum dose of prednisolone and the use of immunosuppressive agents had increased, and the mean dose reduction rate of prednisolone was significantly high. There was no significant difference between patients with and without HLA-B52 allele. CONCLUSIONS: The prognosis of TA patients has improved over the past decade, which may be related to early diagnosis because of the development of noninvasive diagnostic imaging tools and improved medical treatments. PMID- 22301848 TI - Comparison of contrast media and low-molecular-weight dextran for frequency domain optical coherence tomography. AB - BACKGROUND: Although an intracoronary frequency-domain optical coherence tomography (FD-OCT) system overcomes several limitations of the time-domain OCT (TD-OCT) system, the former requires injection of contrast media for image acquisition. The increased total amount of contrast media for FD-OCT image acquisition may lead to the impairment of renal function. The safety and usefulness of the non-occlusion method with low-molecular-weight dextran L (LMD L) via a guiding catheter for TD-OCT image acquisition have been reported previously. The aim of the present study was to compare the image quality and quantitative measurements between contrast media and LMD-L for FD-OCT image acquisition in coronary stented lesions. METHODS AND RESULTS: Twenty-two patients with 25 coronary stented lesions were enrolled in this study. FD-OCT was performed with the continuous-flushing method via a guiding catheter. Both contrast media and LMD-L were infused at a rate of 4 ml/s by an autoinjector. With regard to image quality, the prevalence of clear image segments was comparable between contrast media and LMD-L (97.9% vs. 96.5%, P=0.90). Furthermore, excellent correlations were observed between both flushing solutions in terms of minimum lumen area, mean lumen area, and mean stent area. The total volumes of contrast media and of LMD-L needed for OCT image acquisition were similar. CONCLUSIONS: FD-OCT image acquisition with LMD-L has the potential to reduce the total amount of contrast media without loss of image quality. PMID- 22301849 TI - Is the pre-ejection period key to predicting the response to cardiac resynchronization therapy? PMID- 22301851 TI - STAT5 reins in the follicular helpers. PMID- 22301850 TI - Accessory molecules for Toll-like receptors and their function. AB - Toll-like receptors (TLRs) are essential components of the innate immune system. Accessory proteins are required for the biosynthesis and activation of TLRs. Here, we summarize recent findings on TLR accessory proteins that are required for cell-surface and endosomal TLR function, and we classify these proteins based on their function as ligand-recognition and delivery cofactors, chaperones and trafficking proteins. Because of their essential roles in TLR function, targeting of such accessory proteins may benefit strategies aimed at manipulating TLR activation for therapeutic applications. PMID- 22301852 TI - Interference of a new cyclometallated Pt compound with Cu binding to amyloid-beta peptide. AB - Coordination of a cyclometallated Pt(II) complex (1) to an amyloid-beta peptide was probed by NMR and ESI-MS. Furthermore, EPR showed that binding of 1 to the Cu(II)-amyloid-beta species resulted in a reshuffling of the Cu(II) coordination sphere, which was absent or lower for the sister non cyclometallated Pt(II) complexes. PMID- 22301853 TI - Acitretin, an enhancer of alpha-secretase expression, crosses the blood-brain barrier and is not eliminated by P-glycoprotein. AB - BACKGROUND: ADAM10 (a disintegrin and metalloproteinase 10) has been demonstrated to act as the main physiological alpha-secretase. Enzymatic activity of the alpha secretase on the one hand prevents the formation of toxic Abeta peptides and on the other hand promotes the secretion of a neurotrophic and neuroprotective amyloid precursor protein fragment (APPs-alpha) by cleaving the amyloid precursor protein within its Abeta sequence. Enhancement of ADAM10's gene expression may therefore present a valuable therapeutic approach for the treatment of Alzheimer's disease (AD), where Abeta peptides are severely involved in the pathogenesis. OBJECTIVE: In cell culture and in a transgenic mouse model of AD, retinoids led to increased ADAM10 expression and activity. We therefore endeavor to develop a clinical application of synthetic retinoids such as acitretin in AD. METHODS: The effect of synthetic retinoids on ADAM10 gene expression was analyzed by reporter gene assays in human neuroblastoma cell line SH-SY5Y. Penetrance of acitretin into the murine brain was analyzed by high-performance liquid chromatography. P-glycoprotein (P-gp) double-knockout mice with a deficiency in both isoforms, mdr1a and 1b, were used to analyze a possible role of P-gp dependent efflux on acitretin distribution. RESULTS: Acitretin and tamibarotene are both potent activators of ADAM10 promoter activity. Acitretin crosses the murine blood-brain barrier and its level in the mouse brain is not reduced by P gp. CONCLUSION: Synthetic retinoids and especially acitretin seem to be ideal candidates to establish an ADAM10-based AD treatment, and therefore have already entered first clinical trials. PMID- 22301854 TI - Obesity, a health burden of a global nature. PMID- 22301855 TI - A continued saga of Boc5, the first non-peptidic glucagon-like peptide-1 receptor agonist with in vivo activities. AB - Glucagon-like peptide-1 (GLP-1)-based therapy presents a promising option for treating type 2 diabetes. However, there are several limitations relative to the peptidic GLP-1 mimetics currently on the market or under development. This concern has led to a continued interest in the search for non-peptidic agonists for GLP-1 receptor (GLP-1R). Here, we briefly review the discovery, characterization and current status of a novel class of cyclobutane-derivative based non-peptidic agonists for GLP-1R, including Boc5 and its newly discovered analogue WB4-24. Although the oral bioavailability of such compounds still poses great challenges, the progress made so far encourages us to identify a truly 'druggable' small molecule agonist for GLP-1R. PMID- 22301856 TI - Rare adipose disorders (RADs) masquerading as obesity. AB - Rare adipose disorders (RADs) including multiple symmetric lipomatosis (MSL), lipedema and Dercum's disease (DD) may be misdiagnosed as obesity. Lifestyle changes, such as reduced caloric intake and increased physical activity are standard care for obesity. Although lifestyle changes and bariatric surgery work effectively for the obesity component of RADs, these treatments do not routinely reduce the abnormal subcutaneous adipose tissue (SAT) of RADs. RAD SAT likely results from the growth of a brown stem cell population with secondary lymphatic dysfunction in MSL, or by primary vascular and lymphatic dysfunction in lipedema and DD. People with RADs do not lose SAT from caloric limitation and increased energy expenditure alone. In order to improve recognition of RADs apart from obesity, the diagnostic criteria, histology and pathophysiology of RADs are presented and contrasted to familial partial lipodystrophies, acquired partial lipodystrophies and obesity with which they may be confused. Treatment recommendations focus on evidence-based data and include lymphatic decongestive therapy, medications and supplements that support loss of RAD SAT. Associated RAD conditions including depression, anxiety and pain will improve as healthcare providers learn to identify and adopt alternative treatment regimens for the abnormal SAT component of RADs. Effective dietary and exercise regimens are needed in RAD populations to improve quality of life and construct advanced treatment regimens for future generations. PMID- 22301857 TI - Laboratory animals as surrogate models of human obesity. AB - Obesity and obesity-related metabolic diseases represent a growing socioeconomic problem throughout the world. Great emphasis has been put on establishing treatments for this condition, including pharmacological intervention. However, there are many obstacles and pitfalls in the development process from pre clinical research to the pharmacy counter, and there is no certainty that what has been observed pre-clinically will translate into an improvement in human health. Hence, it is important to test potential new drugs in a valid translational model early in their development. In the current mini-review, a number of monogenetic and polygenic models of obesity will be discussed in view of their translational character. PMID- 22301858 TI - Childhood obesity: a life-long health risk. AB - Childhood obesity has become major health concern for physicians, parents, and health agencies around the world. Childhood obesity is associated with an increased risk for other diseases not only during youth but also later in life, including diabetes, arterial hypertension, coronary artery disease, and fatty liver disease. Importantly, obesity accelerates atherosclerosis progression already in children and young adults. With regard to pathophysiological changes in the vasculature, the striking similarities between physiological changes related to aging and obesity-related abnormalities are compatible with the concept that obesity causes "premature" vascular aging. This article reviews factors underlying the accelerated vascular disease development due to obesity. It also highlights the importance of recognizing childhood obesity as a disease condition and its permissive role in aggravating the development of other diseases. The importance of childhood obesity for disease susceptibility later in life, and the need for prevention and treatment are also discussed. PMID- 22301859 TI - Effects of liraglutide and sibutramine on food intake, palatability, body weight and glucose tolerance in the gubra DIO-rats. AB - AIM: To validate the gubra DIO-rats as a useful animal model of human obesity. METHODS: The gubra diet-induced obesity (DIO) rat model was based on male Sprague Dawley rats with ad libitum access to regular chow and a palatable diet rich in fat and sugar. To evaluate the versatility of the gubra DIO-rats as a valid model of human obesity syndrome, the efficacy of 2 weight loss compounds liraglutide and sibutramine with different mechanisms of action were examined in 7-month-old gubra DIO-rats. Liraglutide (200 MUg/kg, sc) was administered bi-daily, and sibutramine (5 mg/kg, po) was administered once daily for 23 d. RESULTS: Both the compounds effectively reduced the food intake, body weight and total fat mass as measured by nuclear magnetic resonance. Whereas the 5-HT reuptake inhibitor/5-HT receptor agonist sibutramine reduced the intake of both chow and the gubra-diet, the GLP-1 analogue liraglutide predominantly reduced the intake of the highly palatable diet, indicating a shift in food preference. Sibutramine lowered the insulin sensitivity index, primarily via reductions in glucose-stimulated insulin secretion. CONCLUSION: This animal model responds well to 2 weight loss compounds with different mechanisms of action. Moreover, the gubra DIO-rat can be particularly useful for the testing of compounds with potential effects on diet preference. PMID- 22301860 TI - Association of ALOX15 gene polymorphisms with obesity-related phenotypes in Chinese nuclear families with male offspring. AB - AIM: Genetic variation in ALOX12, which encoded human 12-lipoxygenase, was found to be associated with fat mass in young Chinese men. The objective of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) and haplotypes in the ALOX15 gene and obesity-related phenotypes in Chinese nuclear families with male offspring. METHODS: We recruited 1,296 subjects from 427 nuclear families with male offspring and genotyped five SNPs (rs9894225, rs748694, rs2619112, rs2619118, and rs916055) in the ALOX15 gene locus. The total fat mass (TFM), trunk fat mass (tFM), leg fat mass (LFM) and arm fat mass (AFM) were measured using dual-energy X-ray absorptiometry (DXA). The percentage of fat mass (PFM) was the ratio of TFM and body weight. The association between SNPs and haplotypes of ALOX15 and obesity-related phenotypic variation was measured using quantitative transmission disequilibrium test (QTDT). RESULTS: Using QTDT to measure family-based genetic association, we found that rs916055 had a statistically significant association with PFM (P=0.038), whereas rs916055 had a marginal but statistically insignificant association with tFM (P=0.093). The multiple-parameter 1000 permutations test agreed with the family-based association results: both showed that rs916055 had a statistically significant association with PFM (P=0.033). CONCLUSION: rs916055 in ALOX15 gene was significantly associated with the percentage of fat mass in Chinese nuclear families with male offspring in the family-based association study using QTDT approach. PMID- 22301861 TI - Exhaustive swimming differentially inhibits P2X1 receptor- and alpha1 adrenoceptor-mediated vasoconstriction in isolated rat arteries. AB - AIM: To investigate the effects of exhaustive swimming exercise on P2X1 receptor- and alpha1-adrenoceptor-mediated vasoconstriction of different types of arteries in rats. METHODS: Male Wistar rats were divided into 2 groups: the sedentary control group (SCG) and the exhaustive swimming exercise group (ESEG). The rats in the ESEG were subjected to a swim to exhaustion once a day for 2 weeks. Internal carotid, caudal, pulmonary, mesenteric arteries and aorta were dissected out. Isometric vasoconstrictive responses of the arteries to alpha,beta-methylene ATP (alpha,beta-MeATP) or noradrenaline (NA) were recorded using a polygraph. RESULTS: The exhaustive swimming exercise did not produce significant change in the EC(50) values of alpha,beta-MeATP or NA in vasoconstrictive response of most of the arteries studied. The exhaustive swimming exercise inhibited the vasoconstrictive responses to P2X1 receptor activation in the internal carotid artery, whereas it reduced the maximal vasoconstrictive responses to alpha1 adrenoceptor stimulation in the caudal, pulmonary, mesenteric arteries and aorta. The rank order of the reduction of the maximal vasoconstriction was as follows: mesenteric, pulmonary, caudal, aorta. CONCLUSION: Exhaustive swimming exercise differentially affects the P2X1 receptor- and alpha1-adrenoceptor-regulated vasoconstriction in internal carotid artery and peripheral arteries. The ability to preserve purinergic vasoconstriction in the peripheral arteries would be useful to help in maintenance of the basal vascular tone during exhaustive swimming exercise. PMID- 22301862 TI - A novel sulfonamide agent, MPSP-001, exhibits potent activity against human cancer cells in vitro through disruption of microtubule. AB - AIM: To evaluate the anti-cancer effects of a new sulfonamide derivative, 2-(N-(3 chlorophenyl)-4-methoxyphenylsulfonamido)-N-hydroxypropanamide (MPSP-001). METHODS: Human cancer cell lines (HepG2, THP-1, K562, HGC-27, SKOV3, PANC-1, SW480, Kba, HeLa, A549, MDA-MB-453, and MCF-7) were examined. The cytotoxicity of MPSP-001 was evaluated using the WST-8 assay. Cell cycle distribution was examined with flow cytometry. Mitotic spindle formation was detected using immunofluorescence microscopy. Apoptosis-related proteins were examined with Western blot using specific phosphorylated protein antibodies. Competitive tubulin-binding assay was performed to test whether the compound competitively bound to the colchicine site. Molecular docking was performed to explore the possible binding conformation. RESULTS: MPSP-001 potently inhibited the growth of the 12 different types of human cancer cells with the IC(50) values ranging from 1.9 to 15.7 MUmol/L. The compound exerted potent inhibition on the drug-resistant Kb/VCR and MCF-7/ADR cells, as on Kba and MCF-7 cells. In HeLa, HGC-27, A549, and other cells, the compound (5 MUmol/L) caused cell cycle arrest at the G(2)/M phase, and subsequently induced cell apoptosis. In Hela cells, it prevented the mitotic spindle formation. Furthermore, the compound dose-dependently inhibited polymerization of tubulin in vitro, and directly bound to the colchicine-site of beta-tubulin. Molecular docking predicted that the compound may form two hydrogen bonds to the binding pocket. The compound showed synergistic effects with colchicine and taxol in blocking mitosis of HeLa cells. CONCLUSION: MPSP-001 shows a broad-spectrum of anti-tumor efficacy in vitro and represents a novel structure with anti-microtubule activity. PMID- 22301863 TI - Piperonal ciprofloxacin hydrazone induces growth arrest and apoptosis of human hepatocarcinoma SMMC-7721 cells. AB - AIM: To investigate the cytotoxic effects of piperonal ciprofloxacin hydrazone (QNT4), a novel antibacterial fluoroquinolone derivative, against human hepatocarcinoma SMMC-7721 cells. METHODS: Human hepatocarcinoma cells (SMMC 7721), human breast adenocarcinoma cells (MCF-7) and human colon adenocarcinoma cells (HCT-8) were tested. The effects of QNT4 on cell proliferation were examined using MTT assay. Cell apoptosis was determined using Hoechst 33258 fluorescence staining, TUNEL assay and agarose gel electrophoresis. The topoisomerase II activity was measured using agarose gel electrophoresis with the DNA plasmid pBR322 as the substrate. Mitochondrial membrane potential (Deltapsim) was measured using a high content screening imaging system. Protein expression of caspase-9, caspase-8, caspase-3, p53, Bcl-2, Bax, and cytochrome c was detected with Western blot analysis. RESULTS: Treatment with QNT4 (0.625-10 MUmol/L) potently inhibited the proliferation of the cancer cells in time- and dose dependent manners (the IC(50) value at 24 h in SMMC-7721 cells, MCF-7 cells and HCT-8 cells was 2.956+/-0.024, 3.710+/-0.027, and 3.694+/-0.030 MUmol/L, respectively). Treatment of SMMC-7721 cells with QNT4 (0.2146, 2.964, and 4.600 MUmol/L) for 24 h dose-dependently increased the percentage of apoptotic cells, elicited characteristic DNA "ladder" bands, and decreased the mitochondrial membrane potential. QNT4 dose-dependently increased topoisomerase II-mediated DNA breaks while inhibiting DNA relegation, thus keeping the DNA in fragments. Treatment of SMMC-7721 cells with QNT4 significantly increased cytochrome c in the cytosol, and decreased cytochrome c in the mitochondrial compartment. QNT4 (3 7.39 MUmol/L) significantly increased the protein expression of p53, Bax, caspase 9, caspase-3, and the cleaved activated forms of caspase-9 and caspase-3 in SMMC 7721 cells. In contrast, the expression of Bcl-2 was decreased, while caspase-8 had no significant change. CONCLUSION: QNT4 induced the apoptosis of SMMC-7721 cells via inhibiting topoisomerase II activity and modulating mitochondrial dependent pathways. PMID- 22301864 TI - In vitro and in vivo investigation of dexibuprofen derivatives for CNS delivery. AB - AIM: Dexibuprofen, the S(+)-isomer of ibuprofen, is an effective therapeutic agent for the treatment of neurodegenerative disorders. However, its clinical use is hampered by a limited brain distribution. The aim of this study was to design and synthesize brain-targeting dexibuprofen prodrugs and to evaluate their brain targeting efficiency using biodistribution and pharmacokinetic analysis. METHODS: In vitro stability, biodistribution and pharmacokinetic studies were performed on male Sprague-Dawley rats. The concentrations of dexibuprofen in biosamples, including the plasma, brain, heart, liver, spleen, lung, and kidney, were measured using high pressure lipid chromatography (HPLC). The pharmacokinetic parameters of the drug in the plasma and tissues were calculated using obtained data and statistics. RESULTS: Five dexibuprofen prodrugs that were modified to contain ethanolamine-related structures were designed and synthesized. Their chemical structures were confirmed using (1)H NMR, (13)C NMR, IR, and HRMS. In the biodistribution study, 10 min after intravenous administration of dexibuprofen (11.70 mg/kg) and its prodrugs (the dose of each compound was equivalent to 11.70 mg/kg of dexibuprofen) in male Sprague-Dawley rats, the dexibuprofen concentrations in the brain and plasma were measured. The C(brain)/C(plasma) ratios of prodrugs 1, 2, 3, 4, and 5 were 17.0-, 15.7-, 7.88-, 9.31-, and 3.42-fold higher than that of dexibuprofen, respectively (P<0.01). Thus, each of the prodrugs exhibited a significantly enhanced brain distribution when compared with dexibuprofen. In the pharmacokinetic study, prodrug 1 exhibited a brain-targeting index of 11.19 {DTI=(AUC(brain)/AUC(plasma))(1)/(AUC(brain)/AUC(plasma))(dexibuprofen)}. CONCLUSION: The ethanolamine-related structures may play an important role in transport across the brain blood barrier. PMID- 22301865 TI - Effects of exercise training on red blood cell production: implications for anemia. AB - Exercise training can increase total Hb and red cell mass, which enhances oxygen carrying capacity. The possible underlying mechanisms are proposed to come mainly from bone marrow, including stimulated erythropoiesis with hyperplasia of the hematopoietic bone marrow, improvement of the hematopoietic microenvironment induced by exercise training, and hormone- and cytokine-accelerated erythropoiesis. Anemia is one of the most common medical conditions in chronic disease. The effects of exercise training on counteracting anemia have been explored and evaluated. The results of the research available to date are controversial, and it seems that significant methodological limitations exist. However, exercise training might be a promising, additional, safe and economical method to help improve anemia. There is a need for further investigation into the effects of and guidelines for exercise interventions (especially strength training) in this population of patients, particularly among cancer patients who are undergoing or have undergone chemotherapy or radiation treatments. As the available data are limited, additional research to uncover the underlying mechanisms associated with the effects of exercise training on anemia is clearly warranted. PMID- 22301866 TI - Imaging in gout: insights into the pathological features of disease. AB - PURPOSE OF REVIEW: Imaging has the potential to assess various pathological manifestations of gout, including monosodium urate (MSU) crystal deposition, tophus formation and cartilage, soft tissue, and bone pathology. This review discusses recent research examining the role of imaging to assess the manifestations of disease. RECENT FINDINGS: Various imaging techniques are used in the assessment of gout, including plain radiography, ultrasonography, conventional computed tomography (CT), dual energy computed tomography (DECT), and MRI. Potential roles for ultrasonography are MSU crystal detection, measurement of tophi, and assessment of disease complications. Ultrasonography may allow detection of MSU crystals in patients with hyperuricaemia, prior to development of clinically apparent gout. Conventional CT allows excellent visualization of tophi and bone erosion. DECT is a promising method of noninvasive MSU crystal detection. MRI allows assessment of tophi, synovial and soft tissue disease, and bone pathology. The relative absence of MRI bone marrow oedema in gout suggests that the mechanisms of bone erosion in gout are quite different from those in other erosive arthropathies. SUMMARY: Imaging modalities have provided important insights into the pathology of gout. The role of various imaging techniques in gout diagnosis, monitoring, and prediction of outcome is rapidly developing. PMID- 22301867 TI - Up-to-date management of gout. AB - PURPOSE OF REVIEW: Gout is a true crystal deposition disease, extremely painful and bone and tissue damaging if untreated. It is the only curable form of arthritis. Although we have many treatments to cure gout, it is a disease that is consistently undertreated/mismanaged and perceived by clinicians and the lay public as a 'laughable condition' with the patients' lifestyle often held erroneously to account. This article would give you a good understanding of modern and established pharmacological and nonpharmacological treatments used in the management of acute and chronic gout and how to 'treat to target' to cure the disease. RECENT FINDINGS: Many of the drugs we use to manage patients with gouty arthritis have been in existence since the 1970s and 1980s. In the past few years, because of the improved physiological understanding of gout, new innovative treatments such as anti-IL inhibitors, a nonxanthine oxidase inhibitor and the uricase enzymes have been developed adding to our armamentarium of drugs. SUMMARY: With the introduction of new research, we have been able to explore how to also use established treatments more effectively, raising the profile of gout and its best management and introducing the principle of treating the patient to urate target. PMID- 22301868 TI - Drug-induced rheumatic diseases: a review of published case reports from the last two years. AB - PURPOSE OF REVIEW: New drugs are continuously being developed and some rheumatic syndromes have been associated with specific drugs. As most of the rheumatic diseases are multisystem, it is worthwhile examining the wider case report literature to see whether any recent studies signify new associations between drugs and the rheumatic diseases. The last 2 years' case reports in English were scrutinized for noninfectious association with the rheumatic diseases. Cross referencing from MEDLINE was performed using several databases including Google scholar; British Medical Journal (BMJ) case reports were also queried separately. RECENT FINDINGS: Fifty-three articles comprising 56 case reports are included in the review, with 27 (48.2%) associated with the vasculitides, eight (14.3%) associated with lupus and 13 (23.2%) were associated with the myositis syndromes. The commonest four groups of drugs to potentially induce rheumatic diseases were anti-tumour necrosis factor (TNF) drugs, oncology drugs, propylthiouracil and interferons. SUMMARY: It is important to recognise that drugs used in other specialties may induce rheumatic disease and vigilance on making a diagnosis is the key. PMID- 22301869 TI - Current world literature. PMID- 22301871 TI - [High-resolution manometry of the upper esophageal sphincter]. AB - BACKGROUND: High-resolution manometry (HRM) represents a valuable tool for the evaluation of peristalsis in the oesophagus. Due to the wide spacing of the pressure transducers, however, examination of the upper oesophageal sphincter's relaxation period has not proved satisfactory as yet. DESIGN: A feasibility study was carried out to clarify whether evaluation of the upper oesophageal sphincter's behaviour during swallows is possible using a catheter with very closely spaced pressure transducers. SETTING: University hospital. PROCEDURE: Healthy subjects were analysed using a specially developed catheter as well as a modified software to evaluate whether swallow-associated behaviour could be verified. RESULTS: Interpreting pressure profiles in terms of resting pressure, residual pressure, relaxation time and maximum peristaltic pressure proved to be feasible. The present analysis supports the existence of distinct dynamic swallow associated phases, which conform to the phases that had previously been postulated. An additional initial phase, however, should be added. CONCLUSION: This newly created catheter design in combination with the modified software enable a very detailed evaluation of the sphincter's swallow-associated behaviour and represent a valuable, minimally invasive tool with no exposure to radiation for dysphagia diagnosis as well as treatment planning. PMID- 22301872 TI - It takes two to transport, or is it one? PMID- 22301873 TI - Cbl exposes its RING finger. PMID- 22301874 TI - A team effort blocks the ribosome in its tracks. PMID- 22301880 TI - Development of diacyltetrol lipids as activators for the C1 domain of protein kinase C. AB - The protein kinase C (PKC) family of serine/threonine kinases is an attractive drug target for the treatment of cancer and other diseases. Diacylglycerol (DAG), phorbol esters and others act as ligands for the C1 domain of PKC isoforms. Inspection of the crystal structure of the PKCdelta C1b subdomain in complex with phorbol-13-O-acetate shows that one carbonyl group and two hydroxyl groups play pivotal roles in recognition of the C1 domain. To understand the importance of two hydroxyl groups of phorbol esters in PKC binding and to develop effective PKC activators, we synthesized DAG like diacyltetrols (DATs) and studied binding affinities with C1b subdomains of PKCdelta and PKCtheta. DATs, with the stereochemistry of natural DAGs at the sn-2 position, were synthesized from (+) diethyl L-tartrate in four to seven steps as single isomers. The calculated EC(50) values for the short and long chain DATs varied in the range of 3-6 MUM. Furthermore, the fluorescence anisotropy values of the proteins were increased in the presence of DATs in a similar manner to that of DAGs. Molecular docking of DATs (1b-4b) with PKCdelta C1b showed that the DATs form hydrogen bonds with the polar residues and backbone of the protein, at the same binding site, as that of DAG and phorbol esters. Our findings reveal that DATs represent an attractive group of C1 domain ligands that can be used as research tools or further structurally modified for potential drug development. PMID- 22301881 TI - Path-directed and maskless fabrication of ordered TiO2 nanoribbons. AB - Highly ordered TiO(2) nanoribbons with a width from 150 nm to several micrometres and a thickness of 60 nm were fabricated by a path-directed and maskless route. Structural analysis and mechanical properties indicate that the nanoribbons are suited for constructing array-nanodevices. The method exhibits many advantages such as designability, precise size control and good transferability. PMID- 22301882 TI - Use of dimethyl carbonate as a solvent greatly enhances the biaryl coupling of aryl iodides and organoboron reagents without adding any transition metal catalysts. AB - The coupling reaction of aryl iodides with arylboronic acids to give biaryl compounds can be efficiently performed without adding a transition metal catalyst. The key to success is the use of dimethyl carbonate as a solvent. This finding provides a new strategy for constructing a biaryl linkage. PMID- 22301883 TI - Fixation of carbon dioxide by macrocyclic lanthanide(III) complexes under neutral conditions producing self-assembled trimeric carbonato-bridged compounds with MU3 eta2:eta2:eta2 bonding. AB - A series of mononuclear lanthanide(III) complexes [Ln(LH(2))(H(2)O)(3)Cl](ClO(4))(2) (Ln = La, Nd, Sm, Eu, Gd, Tb, Lu) of the tetraiminodiphenolate macrocyclic ligand (LH(2)) in 95 : 5 (v/v) methanol-water solution fix atmospheric carbon dioxide to produce the carbonato-bridged trinuclear complexes [{Ln(LH(2))(H(2)O)Cl}(3)(MU(3)-CO(3))](ClO(4))(4).nH(2)O. Under similar conditions, the mononuclear Y(III) complex forms the dimeric compound [{Y(LH(2))(H(2)O)Cl}(MU(2) CO(3)){Y(LH(2))(H(2)O)(2)}](ClO(4))(3).4H(2)O. These complexes have been characterized by their IR and NMR ((1)H, (13)C) spectra. The X-ray crystal structures have been determined for the trinuclear carbonato-bridged compounds of Nd(III), Gd(III) and Tb(III) and the dinuclear compound of Y(III). In all cases, each of the metal centers are 8-coordinate involving two imine nitrogens and two phenolate oxygens of the macrocyclic ligand (LH(2)) whose two other imines are protonated and intramolecularly hydrogen-bonded with the phenolate oxygens. The oxygen atoms of the carbonate anion in the trinuclear complexes are bonded to the metal ions in tris-bidentate MU(3)-eta(2):eta(2):eta(2) fashion, while they are in bis-bidentate MU(2)-eta(2):eta(2) mode in the Y(III) complex. The magnetic properties of the Gd(III) complex have been studied over the temperature range 2 to 300 K and the magnetic susceptibility data indicate a very weak antiferromagnetic exchange interaction (J = -0.042 cm(-1)) between the Gd(III) centers (S = 7/2) in the metal triangle through the carbonate bridge. The luminescence spectral behaviors of the complexes of Sm(III), Eu(III), and Tb(III) have been studied. The ligand LH(2) acts as a sensitizer for the metal ions in an acetonitrile-toluene glassy matrix (at 77 K) and luminescence intensities of the complexes decrease in the order Eu(3+) > Sm(3+) > Tb(3+). PMID- 22301884 TI - Antisense inhibition of apoB synthesis with mipomersen reduces plasma apoC-III and apoC-III-containing lipoproteins. AB - Mipomersen, an antisense oligonucleotide that reduces hepatic production of apoB, has been shown in phase 2 studies to decrease plasma apoB, LDL cholesterol (LDL C), and triglycerides. ApoC-III inhibits VLDL and LDL clearance, and it stimulates inflammatory responses in vascular cells. Concentrations of VLDL or LDL with apoC-III independently predict cardiovascular disease. We performed an exploratory posthoc analysis on a subset of hypercholesterolemic subjects obtained from a randomized controlled dose-ranging phase 2 study of mipomersen receiving 100, 200, or 300 mg/wk, or placebo for 13 wk (n = 8 each). ApoC-III containing lipoproteins were isolated by immuno-affinity chromatography and ultracentrifugation. Mipomersen 200 and 300 mg/wk reduced total apoC-III from baseline by 6 mg/dl (38-42%) compared with placebo group (P < 0.01), and it reduced apoC-III in both apoB lipoproteins and HDL. Mipomersen 100, 200, and 300 mg doses reduced apoB concentration of LDL with apoC-III (27%, 38%, and 46%; P < 0.05). Mipomersen reduced apoC-III concentration in HDL. The drug had no effect on apoE concentration in total plasma and in apoB lipoproteins. In summary, antisense inhibition of apoB synthesis reduced plasma concentrations of apoC-III and apoC-III-containing lipoproteins. Lower concentrations of apoC-III and LDL with apoC-III are associated with reduced risk of coronary heart disease (CHD) in epidemiologic studies independent of traditional risk factors. PMID- 22301885 TI - Do additional cores from MRI cancer-suspicious lesions to systematic 12-core transrectal prostate biopsy give better cancer detection? AB - BACKGROUND: The comparison of systematic prostate biopsies (PBx) with PBx including additional cores based on magnetic resonance imaging (MRI) of lesions suspicious for prostate cancer (PCa) has been controversial. This study focuses on additional cores based on MRI findings for better cancer detection. METHODS: Data were collected from 491 men who underwent transrectal ultrasound-guided PBx: a 12-core PBx (group 1: 395 cases) and a 12-core PBx plus 1-3 additional cores based on MRI (group 2: 96 cases). Comparison of two groups revealed how the additional cores taken with MRI findings affected PCa detection. RESULTS: Group 1 had 205 cases (51.9%) and group 2 had 55 cases (57.3%) of PCa detected. This difference was not statistically significant (p = 0.3444). Only 1 of the 55 patients (1.82%) in group 2 had cancer only in the additional cores based on MRI. In other words, only 1/96 (1.04%) patients was diagnosed with PCa only by the additional core PBx. CONCLUSIONS: We suggest that systematic 12-core PBx (sextant peripheral zone + 4 transitional zone + 2 far lateral peripheral zone) can be considered an excellent tool for PCa detection and there may be no need for additional cores based on MRI findings for PCa detection. PMID- 22301886 TI - Dynamic changes of the Golgi apparatus during bovine in vitro oocyte maturation. AB - For successful fertilization by the male gamete, oocyte cytoplasmic organelles such as the Golgi apparatus have to undergo specific changes: the entire process is known as cytoplasmic maturation. The goal of this study was to unravel the dynamics of the Golgi apparatus in bovine oocytes at critical stages of in vitro maturation, i.e. germinal vesicle (GV), GV breakdown (GVBD), metaphase I (MI) and metaphase II, and to investigate the role of various molecules critically involved therein. The cytoplasmic distribution of proteins was assessed by immunocytochemistry and laser confocal microscopy. We applied specific inhibitors, including nocodazole to unravel the functional role of the microtubular elements; sodium orthovanadate, which primarily inhibits cytoplasmic dynein ATPase activity; monastrol which inhibits the kinesin EG5; and roscovitine to inhibit the kinase cyclin-dependent kinase 2A (CDC2A). Prior to GVBD, the Golgi apparatus was translocated from the centre of the cytoplasm to the cortical area in the periphery, where it underwent fragmentation. A second translocation was observed between GVBD and MI stages, when the Golgi apparatus was moved from the cortex to the centre of the cytoplasm. Incubation with the specific inhibitors revealed that microtubules played an active role in the final localization at GVBD, while CDC2A was essential for Golgi fragmentation at GVBD stage. This partitioning was a precondition for the second movement. In conclusion, for the first time we show basic mechanisms critically involved in the regulation of the dynamic changes of Golgi apparatus during meiosis of the bovine oocyte. PMID- 22301887 TI - The primordial follicle reserve is not renewed after chemical or gamma irradiation mediated depletion. AB - Reports indicate that germ-line stem cells present in adult mice can rapidly generate new oocytes and contribute to the primordial follicle reserve following conditions of ovotoxic stress. We further investigated the hypothesis that adult mice have the capacity to generate new oocytes by monitoring primordial follicle numbers throughout postnatal life and following depletion of the primordial follicle reserve by exposure to doxorubicin (DXR), trichostatin A (TSA), or whole body gamma-irradiation. We show that primordial follicle number remains stable in adult C57BL/6 mice between the ages of 25 and 100 days. However, within 2 days of treatment with DXR or TSA, primordial follicle numbers had declined to 65 and 51% respectively (P<0.05-0.01 when compared to untreated controls), with no restoration of follicle numbers evident after 7 days for either treatment. Furthermore, ovaries from mice subjected to sterilizing doses of gamma irradiation (0.45 or 4.5 Gy) revealed complete ablation of all primordial follicles 5 days after treatment, with no indication of follicular renewal. We conclude that neo-folliculogenesis does not occur following chemical or gamma irradiation mediated depletion of the primordial follicle reserve. PMID- 22301888 TI - Simultaneous occurrence of biphenotypic T cell/myeloid lesions involving t(12;13)(p13;q14) in a pediatric patient. AB - This paper chronicles a 2-year-old girl who presented with acute leukemia/lymphoma syndrome of the T cell immunophenotype. At this time, the cytogenetic analysis of her bone marrow cells showed a reciprocal translocation between the short arm of chromosome 12 and the long arm of chromosome 13, t(12;13)(p13;q14). The immunophenotyping of bone marrow blast cells by flow cytometry revealed a population of cells positive for CD56, CD117, CD45, partial CD33, partial HLA-DR, CD13, CD7, CD2 and CD5. Therefore, a diagnosis of acute leukemia with a mixed T cell/myeloid phenotype was made. The patient had a poor response to classic T cell acute lymphocytic leukemia/lymphoma therapy; thus, her treatment was changed to a myeloid leukemia protocol, which produced a good response. She underwent a successful cord blood transplantation from an unrelated HLA partially matched donor. The coexistence of these two phenotypes prompts questions about the existence of clonal instability, which might influence the choice of therapy. The rarity of the t(12;13)(p13;q14) and the coexistence of T cell/myeloid markers suggest a nonrandom association. To the best of our knowledge, this is the first reported case in which a cell clone bearing a t(12;13)(p13;q14) translocation in a mixed T cell/myeloid lesion was detected. PMID- 22301889 TI - Microsatellite primers in the Chinese dove tree, Davidia involucrata (Cornaceae), a relic species of the Tertiary. AB - PREMISE OF THE STUDY: The first microsatellite primers were developed for Davidia involucrata, an endangered relic species of the Tertiary in China, to further describe its genetic variability and population structure. METHODS AND RESULTS: Using the Fast Isolation by AFLP of Sequences Containing Repeats (FIASCO) protocol, 15 polymorphic microsatellite loci were isolated and characterized in 20 individuals from the germplasm collections of D. involucrata at the Hunan Forest Botanical Garden. High levels of polymorphism were revealed, with the total number of alleles per locus and the number of alleles per locus per individual ranging from two to 13 and from one to six, respectively. CONCLUSIONS: The multibanded patterns of microsatellite loci obtained in the current study confirmed that D. involucrata might be a polyploid species. The primers will be useful for studies of genetic diversity and for guiding conservation strategies for D. involucrata. PMID- 22301890 TI - Phylogenomic analysis of transcriptome data elucidates co-occurrence of a paleopolyploid event and the origin of bimodal karyotypes in Agavoideae (Asparagaceae). AB - PREMISE OF THE STUDY: The stability of the bimodal karyotype found in Agave and closely related species has long interested botanists. The origin of the bimodal karyotype has been attributed to allopolyploidy, but this hypothesis has not been tested. Next-generation transcriptome sequence data were used to test whether a paleopolyploid event occurred on the same branch of the Agavoideae phylogenetic tree as the origin of the Yucca-Agave bimodal karyotype. METHODS: Illumina RNA seq data were generated for phylogenetically strategic species in Agavoideae. Paleopolyploidy was inferred in analyses of frequency plots for synonymous substitutions per synonymous site (K(s)) between Hosta, Agave, and Chlorophytum paralogous and orthologous gene pairs. Phylogenies of gene families including paralogous genes for these species and outgroup species were estimated to place inferred paleopolyploid events on a species tree. KEY RESULTS: K(s) frequency plots suggested paleopolyploid events in the history of the genera Agave, Hosta, and Chlorophytum. Phylogenetic analyses of gene families estimated from transcriptome data revealed two polyploid events: one predating the last common ancestor of Agave and Hosta and one within the lineage leading to Chlorophytum. CONCLUSIONS: We found that polyploidy and the origin of the Yucca-Agave bimodal karyotype co-occur on the same lineage consistent with the hypothesis that the bimodal karyotype is a consequence of allopolyploidy. We discuss this and alternative mechanisms for the formation of the Yucca-Agave bimodal karyotype. More generally, we illustrate how the use of next-generation sequencing technology is a cost-efficient means for assessing genome evolution in nonmodel species. PMID- 22301891 TI - Development of novel low-copy nuclear markers for Hieraciinae (Asteraceae) and their perspective for other tribes. AB - PREMISE OF THE STUDY: The development of three low-copy nuclear markers for low taxonomic level phylogenies in Asteraceae with emphasis on the subtribe Hieraciinae is reported. METHODS AND RESULTS: Marker candidates were selected by comparing a Lactuca complementary DNA (cDNA) library with public DNA sequence databases. Interspecific variation and phylogenetic signal of the selected genes were investigated for diploid taxa from the subtribe Hieraciinae and compared to a reference phylogeny. Their ability to cross-amplify was assessed for other Asteraceae tribes. All three markers had higher variation (2.1-4.5 times) than the internal transcribed spacer (ITS) in Hieraciinae. Cross-amplification was successful in at least seven other tribes of the Asteraceae. Only three cases indicating the presence of paralogs or pseudogenes were detected. CONCLUSIONS: The results demonstrate the potential of these markers for phylogeny reconstruction in the Hieraciinae as well as in other Asteraceae tribes, especially for very closely related species. PMID- 22301892 TI - Next-generation sequencing-based transcriptomic and proteomic analysis of the common reed, Phragmites australis (Poaceae), reveals genes involved in invasiveness and rhizome specificity. AB - PREMISE OF THE STUDY: The common reed (Phragmites australis), one of the most widely distributed of all angiosperms, uses its rhizomes (underground stems) to invade new territory, making it one of the most successful weedy species worldwide. Characterization of the rhizome transcriptome and proteome is needed to identify candidate genes and proteins involved in rhizome growth, development, metabolism, and invasiveness. METHODS: We employed next-generation sequencing technologies including 454 and Illumina platforms to characterize the reed rhizome transcriptome and used quantitative proteomics techniques to identify the rhizome proteome. KEY RESULTS: Combining 336514 Roche 454 Titanium reads and 103350802 Illumina paired-end reads in a de novo hybrid assembly yielded 124450 unique transcripts with an average length of 549 bp, of which 54317 were annotated. Rhizome-specific and differentially expressed transcripts were identified between rhizome apical tips (apical meristematic region) and rhizome elongation zones. A total of 1280 nonredundant proteins were identified and quantified using GeLC-MS/MS based label-free proteomics, where 174 and 77 proteins were preferentially expressed in the rhizome elongation zone and apical tip tissues, respectively. Genes involved in allelopathy and in controlling development and potentially invasiveness were identified. CONCLUSIONS: In addition to being a valuable sequence and protein data resource for studying plant rhizome species, our results provide useful insights into identifying specific genes and proteins with potential roles in rhizome differentiation, development, and function. PMID- 22301893 TI - Coverage-based consensus calling (CbCC) of short sequence reads and comparison of CbCC results to identify SNPs in chickpea (Cicer arietinum; Fabaceae), a crop species without a reference genome. AB - PREMISE OF THE STUDY: Next-generation sequencing (NGS) technologies are frequently used for resequencing and mining of single nucleotide polymorphisms (SNPs) by comparison to a reference genome. In crop species such as chickpea (Cicer arietinum) that lack a reference genome sequence, NGS-based SNP discovery is a challenge. Therefore, unlike probability-based statistical approaches for consensus calling and by comparison with a reference sequence, a coverage-based consensus calling (CbCC) approach was applied and two genotypes were compared for SNP identification. METHODS: A CbCC approach is used in this study with four commonly used short read alignment tools (Maq, Bowtie, Novoalign, and SOAP2) and 15.7 and 22.1 million Illumina reads for chickpea genotypes ICC4958 and ICC1882, together with the chickpea trancriptome assembly (CaTA). KEY RESULTS: A nonredundant set of 4543 SNPs was identified between two chickpea genotypes. Experimental validation of 224 randomly selected SNPs showed superiority of Maq among individual tools, as 50.0% of SNPs predicted by Maq were true SNPs. For combinations of two tools, greatest accuracy (55.7%) was reported for Maq and Bowtie, with a combination of Bowtie, Maq, and Novoalign identifying 61.5% true SNPs. SNP prediction accuracy generally increased with increasing reads depth. CONCLUSIONS: This study provides a benchmark comparison of tools as well as read depths for four commonly used tools for NGS SNP discovery in a crop species without a reference genome sequence. In addition, a large number of SNPs have been identified in chickpea that would be useful for molecular breeding. PMID- 22301894 TI - Burial increases seed longevity of two Artemisia tridentata (Asteraceae) subspecies. AB - PREMISE OF THE STUDY: Seed longevity and persistence in soil seed banks may be especially important for population persistence in ecosystems where opportunities for seedling establishment and disturbance are unpredictable. The fire regime, an important driver of population dynamics in sagebrush steppe ecosystems, has been altered by exotic annual grass invasion. Soil seed banks may play an active role in postfire recovery of the foundation shrub Artemisia tridentata, yet conditions under which seeds persist are largely unknown. METHODS: We investigated seed longevity of two Artemisia tridentata subspecies in situ by retrieving seed bags that were placed at varying depths over a 2 yr period. We also sampled naturally dispersed seeds in litter and soil immediately after seed dispersal and before flowering in subsequent seasons to estimate seed persistence. KEY RESULTS: After 24 mo, seeds buried at least 3 cm below the soil surface retained 30-40% viability whereas viability of seeds on the surface and under litter declined to 0 and < 11%, respectively. The density of naturally dispersed seeds in the seed bank was highly heterogeneous both spatially and temporally, and attrition varied significantly by region. CONCLUSIONS: Our study suggests that Artemisia tridentata has the potential to form a short-term soil seed bank that persists longer than has been commonly assumed, and that burial is necessary for seed longevity. Use of seeding techniques that promote burial of some seeds to aid in formation of a soil seed bank may increase restoration potential. PMID- 22301895 TI - Ultra-barcoding in cacao (Theobroma spp.; Malvaceae) using whole chloroplast genomes and nuclear ribosomal DNA. AB - PREMISE OF STUDY: To reliably identify lineages below the species level such as subspecies or varieties, we propose an extension to DNA-barcoding using next generation sequencing to produce whole organellar genomes and substantial nuclear ribosomal sequence. Because this method uses much longer versions of the traditional DNA-barcoding loci in the plastid and ribosomal DNA, we call our approach ultra-barcoding (UBC). METHODS: We used high-throughput next-generation sequencing to scan the genome and generate reliable sequence of high copy number regions. Using this method, we examined whole plastid genomes as well as nearly 6000 bases of nuclear ribosomal DNA sequences for nine genotypes of Theobroma cacao and an individual of the related species T. grandiflorum, as well as an additional publicly available whole plastid genome of T. cacao. KEY RESULTS: All individuals of T. cacao examined were uniquely distinguished, and evidence of reticulation and gene flow was observed. Sequence variation was observed in some of the canonical barcoding regions between species, but other regions of the chloroplast were more variable both within species and between species, as were ribosomal spacers. Furthermore, no single region provides the level of data available using the complete plastid genome and rDNA. CONCLUSIONS: Our data demonstrate that UBC is a viable, increasingly cost-effective approach for reliably distinguishing varieties and even individual genotypes of T. cacao. This approach shows great promise for applications where very closely related or interbreeding taxa must be distinguished. PMID- 22301896 TI - A comparative transcriptomic study of an allotetraploid and its diploid progenitors illustrates the unique advantages and challenges of RNA-seq in plant species. AB - PREMISE OF THE STUDY: RNA-seq analysis of plant transcriptomes poses unique challenges due to the highly duplicated nature of plant genomes. We address these challenges in the context of recently formed polyploid species and detail an RNA seq experiment comparing the leaf transcriptome profile of an allopolyploid relative of soybean with the diploid species that contributed its homoeologous genomes. METHODS: RNA-seq reads were obtained from the three species and were aligned against the genome sequence of Glycine max. Transcript levels were estimated for each gene, relative contributions of polyploidy-duplicated loci (homoeologues) in the tetraploid were identified, and comparisons of transcript profiles and individual genes were used to analyze the regulation of transcript levels. KEY RESULTS: We present a novel metric developed to address issues arising from high degrees of gene space duplication and a method for dissecting a gene's measured transcript level in a polyploid species into the relative contribution of its homoeologues. We identify the gene family likely contributing to differences in photosynthetic rate between the allotetraploid and its progenitors and show that the tetraploid appears to be using the "redundant" gene copies in novel ways. CONCLUSIONS: Given the prevalence of polyploidy events in plants, we believe many of the approaches developed here to be applicable, and often necessary, in most plant RNA-seq experiments. The deep sampling provided by RNA-seq allows us to dissect the genetic underpinnings of specific phenotypes as well as examine complex interactions within polyploid genomes. PMID- 22301897 TI - Strategies for transcriptome analysis in nonmodel plants. AB - Even with recent reductions in sequencing costs, most plants lack the genomic resources required for successful short-read transcriptome analyses as performed routinely in model species. Several approaches for the analysis of short-read transcriptome data are reviewed for nonmodel species for which the genome of a close relative is used as the reference genome. Two approaches using a data set from Phytophthora-challenged Rubus idaeus (red raspberry) are compared. Over 70000000 86-nt Illumina reads derived from R. idaeus roots were aligned to the Fragaria vesca genome using publicly available informatics tools (Bowtie/TopHat and Cufflinks). Alignment identified 16956 putatively expressed genes. De novo assembly was performed with the same data set and a publicly available transcriptome assembler (Trinity). A BLAST search with a maximum e-value threshold of 1.0 * 10(-3) revealed that over 36000 transcripts had matches to plants and over 500 to Phytophthora. Gene expression estimates from alignment to F. vesca and de novo assembly were compared for raspberry (Pearson's correlation = 0.730). Together, alignment to the genome of a close relative and de novo assembly constitute a powerful method of transcriptome analysis in nonmodel organisms. Alignment to the genome of a close relative provides a framework for differential expression testing if alignments are made to the predefined gene space of a close relative and de novo assembly provides a more robust method of identifying unique sequences and sequences from other organisms in a system. These methods are considered experimental in nonmodel systems, but can be used to generate resources and specific testable hypotheses. PMID- 22301898 TI - Current world literature. PMID- 22301900 TI - Demystifying peer review. PMID- 22301901 TI - Willingness to pay for obesity pharmacotherapy. AB - Several treatments for obesity have received regulatory approval, but health insurers and other payers typically refuse to support access to them. Thus, patients are left to bear significant out-of-pocket costs for obesity pharmacotherapy. This study aimed to assess preferences and willingness to pay (WTP) for obesity medications among people seeking weight loss in the United States and United Kingdom. An online survey was developed based on literature review, clinician interviews, and profiles of available therapies. Participants indicated their preference for hypothetical treatments which varied by seven attributes: percentage of weight loss, long-term health risk reduction, time to noticeable weight loss, delivery mode, side effects, lifestyle modification, and cost; 502 obese participants completed the survey (mean BMI 37.12 kg/m(2) (+/ 4.63); 73.5% female; 47.7 (+/-12.9) years of age). The participants deemed weight loss of >21 kg (United Kingdom) and >28 kg (United State) as "acceptable". All treatment attributes were important (P < 0.001) except "time to noticeable weight loss." The survey found that percentage weight loss was the most important factor for patients and a reduction in long-term health risk was relatively less important. Patients were willing to pay L6.51/$10.49 per month per percentage point of weight loss that a pharmacotherapy could provide. Participants also highly valued therapies that did not require substantial lifestyle modifications and were willing to pay L17.78/$30.77 more per month for a one-pill-per-day treatment vs. a weekly injectable. Participants placed a high value on weight loss and avoiding changes to their lifestyle, and less value on reducing long term risks to health. PMID- 22301902 TI - Validation of five simple models estimating body fat in white postmenopausal women: use in clinical practice and research. AB - The aim of this study was to validate noninvasive models, retrieved from the literature, estimating body fat in white women. The cohort used for the validation consisted of 277 postmenopausal women, and the reference method was dual-energy X-ray absorptiometry (DXA). Five models were retrieved containing anthropometric measurements such as bicep and tricep skinfolds, waist circumference (WC), height, and body weight. Models including only BMI were found to be less biased and more valid than others including skinfolds and circumferences. The model by Visser et al., estimating body density (BD = 0.0226 * sex - 0.0022 * BMI + 1.0605) with the subsequent use of Brozek's (and not Siri's) equation to estimate body fat percentage (%BF), was found to be more valid than the other models for this cohort. In conclusion, it seems that Visser's et al. model, including only BMI, with Brozek's equation, is a fast, noninvasive, and valid method to assess body composition in white postmenopausal women in clinical practice and research. PMID- 22301903 TI - Association of fibrillin-3 and transcription factor-7-like 2 gene variants with metabolic phenotypes in PCOS. AB - Polycystic ovary syndrome (PCOS) is a complex genetic disease characterized by heritable reproductive and metabolic abnormalities. Genetic variants associated with the reproductive phenotype have been mapped to the fibrillin-3 (FBN3) gene and to a novel transcription factor-7-like 2 (TCF7L2) locus (rs11196236 G). The association of these genetic variants with metabolic phenotypes was investigated in 31 PCOS and 18 control women of European ancestry. The insulinogenic index during an oral glucose tolerance test (DeltaI30/DeltaG30) and insulin secretion rates at the maximal dose during a graded-glucose infusion (ISRmax) were used as indexes of insulin secretion. Endogenous glucose production (EGP) and insulin sensitivity (M/I) were determined during a euglycemic clamp. The disposition index (DI) was calculated using M/I and DeltaI30/DeltaG30 or ISRmax. Compared with noncarriers (n = 10) and control (n = 10), M/I was decreased (P = 1.1 * 10( 5)) in heterozygous and homozygous PCOS carriers (n = 14) of rs11196236 G and this variant predicted M/I (partial r(2) = 0.34, P = 0.005) in a regression analysis. Postabsorptive EGP tended to be higher (P = 0.040) in heterozygous and homozygous PCOS carriers of the FBN3-associated allele (n = 12), allele 8 of D19S884 (FBN3(+)), compared to PCOS noncarriers (n = 19). PCOS carriers of the rs12255372 T (TCF7L2 Caucasian type 2 diabetes mellitus (T2D) locus) had no significant associated metabolic phenotypes. We conclude that rs11196236 G TCF7L2 variant is associated with peripheral insulin resistance in PCOS but this effect is not seen in control women. The FBN3 risk allele may be associated with changes in basal glucose homeostasis in PCOS. These findings require replication in additional PCOS cohorts. PMID- 22301904 TI - Optimized TAL effector nucleases (TALENs) for use in treatment of sickle cell disease. AB - TAL effector nucleases (TALENs) represent a new class of artificial nucleases capable of cleaving long, specific target DNA sequences in vivo and are powerful tools for genome editing with potential therapeutic applications. Here we report a pair of custom-designed TALENs for targeted genetic correction of the sickle cell disease mutation in human cells, which represents an example of engineered TALENs capable of recognizing and cleaving a human disease-associated gene. By using a yeast reporter system, a systematic study was carried out to optimize TALEN architecture for maximal in vivo cleavage efficiency. In contrast to the previous reports, the engineered TALENs were capable of recognizing and cleaving target binding sites preceded by A, C or G. More importantly, the optimized TALENs efficiently cleaved a target sequence within the human beta-globin (HBB) gene associated with sickle cell disease and increased the efficiency of targeted gene repair by >1000-fold in human cells. In addition, these TALENs showed no detectable cytotoxicity. These results demonstrate the potential of optimized TALENs as a powerful genome editing tool for therapeutic applications. PMID- 22301906 TI - Development of selective markers linked to a major QTL for parthenocarpy in eggplant (Solanum melongena L.). AB - Parthenocarpy, the ability to set fruits without pollination, is a useful trait for setting fruit under unfavorable conditions. To identify the loci controlling parthenocarpy in eggplant (Solanum melongena L.), we constructed linkage maps by using co-dominant simple sequence repeat and single nucleotide polymorphism markers in F(2) populations derived from intraspecific crosses between two non parthenocarpic lines (LS1934 and Nakate-Shinkuro) and a parthenocarpic line (AE P03). Total map distances were 1,414.6 cM (ALF2: LS1934 x AE-P03) and 1,153.8 cM (NAF2: Nakate-Shinkuro x AE-P03), respectively. Quantitative trait locus (QTL) analyses revealed two QTLs on chromosomes 3 and 8, which we denoted as Controlling parthenocarpy3.1 (Cop3.1) and Cop8.1, respectively. The percentage of phenotypic variance explained (PVE) of Cop3.1 was 6.3% in ALF2 (LOD = 4.2) and 10.6% in NAF2 (LOD = 3.0). The PVE of Cop8.1 was 45.7% in ALF2 (LOD = 23.8) and 29.7% in NAF2 (LOD = 7.9). Using a population of backcross inbred lines, we confirmed the effect of Cop8.1, but there was no evidence to support the contribution of Cop3.1. We need to verify the effect of Cop3.1 under various temperature conditions. In addition, we clarified the effectiveness of selective SSR markers, emf21H22 and emh11J10, mapped on each side of Cop8.1 in other F(2) populations derived from various parental combinations. This is the first report concerning QTL analysis of parthenocarpy in eggplant using molecular markers. It will be useful in marker-assisted selection and in revealing the genomic mechanism underlying parthenocarpy in eggplant. PMID- 22301907 TI - EST-derived genic molecular markers: development and utilization for generating an advanced transcript map of chickpea. AB - Well-saturated linkage maps especially those based on expressed sequence tag (EST)-derived genic molecular markers (GMMs) are a pre-requisite for molecular breeding. This is especially true in important legumes such as chickpea where few simple sequence repeats (SSR) and even fewer GMM-based maps have been developed. Therefore, in this study, 2,496 ESTs were generated from chickpea seeds and utilized for the development of 487 novel EST-derived functional markers which included 125 EST-SSRs, 151 intron targeted primers (ITPs), 109 expressed sequence tag polymorphisms (ESTPs), and 102 single nucleotide polymorphisms (SNPs). Whereas ESTSSRs, ITPs, and ESTPs were developed by in silico analysis of the developed EST sequences, SNPs were identified by allele resequencing and their genotyping was performedusing the Illumina GoldenGate Assay. Parental polymorphism was analyzed between C. arietinum ICC4958 and C. reticulatum PI489777, parents of the reference chickpea mapping population, using a total of 872 markers: 487 new gene-based markers developed in this study along with 385 previously published markers, of which 318 (36.5%) were found to be polymorphic and were used for genotyping. The genotypic data were integrated with the previously published data of 108 markers and an advanced linkage map was generated that contained 406 loci distributed on eight linkage groups that spanned 1,497.7 cM. The average marker density was 3.68 cM and the average number of markers per LG was 50.8. Among the mapped markers, 303 new genomic locations were defined that included 177 gene-based and 126 gSSRs (genomic SSRs) thereby producing the most advanced gene-rich map of chickpea solely based on co-dominant markers. PMID- 22301908 TI - Roles of thioredoxin and thioredoxin reductase in the resistance to oxidative stress in Lactobacillus casei. AB - The Lactobacillus casei strain Shirota used in this study has in the genome four putative thioredoxin genes designated trxA1, trxA2, trxA3 and trxA4, and one putative thioredoxin reductase gene designated trxB. To elucidate the roles of the thioredoxins and the thioredoxin reductase against oxidative stress in L. casei, we constructed gene disruption mutants, in which each of the genes trxA1, trxA2 and trxB, or both trxA1 and trxA2 were disrupted, and we characterized their growth and response to oxidative stresses. In aerobic conditions, the trxA1 (MS108) and the trxA2 (MS109) mutants had moderate growth defects, and the trxA1 trxA2 double mutant (MS110) had a severe growth defect, which was characterized by elongation of doubling time and a lower final turbidity level. Furthermore, the trxB mutant (MS111), which is defective in thioredoxin reductase, lost the ability to grow under aerobic conditions, although it grew partially under anaerobic conditions. The growth of these mutants, however, could be substantially restored by the addition of dithiothreitol or reduced glutathione. In addition, MS110 and MS111 were more sensitive to hydrogen peroxide and disulfide stress than the wild-type. In particular, the stress sensitivity of MS111 was significantly increased. On the other hand, transcription of all these genes was only weakly affected by these oxidative stresses. Taken together, these results suggest that the thioredoxin-thioredoxin reductase system is the major thiol/disulfide redox system and is essential to allow the facultative anaerobe L. casei to grow under aerobic conditions. PMID- 22301909 TI - NdnR is an NAD-responsive transcriptional repressor of the ndnR operon involved in NAD de novo biosynthesis in Corynebacterium glutamicum. AB - The Corynebacterium glutamicum ndnR gene, which is chromosomally located in a gene cluster involved in NAD de novo biosynthesis, negatively regulates expression of the cluster genes, i.e. nadA, nadC, nadS and ndnR itself. Although ndnR encodes a member of the recently identified NrtR family of transcriptional regulators, whether or not the NdnR protein directly regulates these NAD biosynthesis genes remains to be verified. Here, two NdnR binding sites in the promoter region of the ndnR-nadA-nadC-nadS operon in C. glutamicum were confirmed by in vitro DNA binding assay and analysis of in vivo expression of the chromosomally integrated ndnR promoter-lacZ reporter fusion. Electrophoretic mobility shift assay revealed that the NdnR protein binds to the 5'-upstream region of ndnR, and that the binding is significantly enhanced by NAD. Mutation in two 21 bp NdnR binding motifs in the ndnR promoter region inhibited the binding of NdnR in vitro. The mutation also enhanced the promoter activity in cells cultured in the presence of nicotinate, which is utilized in NAD biosynthesis, resulting in the loss of the repression in response to an exogenous NAD precursor; this is consistent with the effect of deletion of ndnR reported in our previous study. These results indicate that NAD acts as a co-repressor for the NdnR protein that directly regulates the ndnR operon involved in NAD de novo biosynthesis; the NAD-NdnR regulatory system likely plays an important role in the control of NAD homeostasis in C. glutamicum. PMID- 22301910 TI - Multiple deletions reveal the essentiality of the DedA membrane protein family in Escherichia coli. AB - The DedA family is a highly conserved, ancient family of membrane proteins with representatives in most sequenced genomes. A characteristic of prokaryotic DedA family genes is extensive gene duplication, with most bacterial genomes carrying two or more homologues. The Escherichia coli genome carries eight DedA genes, each individually nonessential. We previously described an E. coli mutant (BC202; DeltayghB : : kan(R), DeltayqjA : : tet(R)) with in-frame deletions of two DedA genes encoding proteins with 61 % amino acid identity. BC202 fails to complete cell division or grow at elevated temperatures. Here, we report that restoration of normal growth and cell division of BC202 is possible by overexpression of a subset of the eight E. coli DedA genes (yabI, yohD, yqjA and yghB) but not others (dedA, ydjX, ydjZ and yqaA), suggesting the existence of two functional groups within the family. We have constructed individual E. coli strains in which all eight DedA genes are deleted in a nonpolar manner, and growth is supported by a single DedA family gene under control of an inducible promoter. Strain BAL801 (with growth supported by cloned dedA) and BAL802 (with growth supported by cloned yqjA) exhibit slow growth that is absolutely dependent upon the presence of the arabinose inducer. Growth in the presence of glucose results in cell death. These results indicate that while not individually essential, the E. coli DedA family proteins are collectively essential. These observations suggest important functions for the E. coli DedA protein family. PMID- 22301911 TI - A novel GlnR target gene, nnaR, is involved in nitrate/nitrite assimilation in Streptomyces coelicolor. AB - GlnR is the global transcriptional regulator of nitrogen assimilation in Streptomyces coelicolor. Under nitrogen starvation, GlnR controls the transcription of at least nine genes associated with nitrogen metabolism. In this study, we identified a new GlnR target gene, SCO2958, named nnaR (nitrate/nitrite assimilation regulator). In silico analysis of NnaR revealed the presence of two distinct domains: an N-terminal uroporphyrinogen-III synthase (HemD)-like enzymatic domain and a C-terminal DNA binding domain. Complementation experiments with a haemin auxotroph Escherichia coli DeltahemD mutant strain revealed that NnaR has no HemD activity. Physiological studies of an S. coelicolor nnaR : : Tn5062 mutant showed that NnaR is involved in regulating nitrite reduction. By electrophoretic mobility shift assays the functionality of the NnaR DNA binding domain was confirmed, and it was found that NnaR binds in front of the genes narK (putative nitrate extrusion protein), nirB (nitrite reductase), nirA (putative nitrite/sulphite reductase) and nasA (putative nitrate reductase), which are associated with nitrate/nitrite assimilation. Furthermore, a cooperative binding of NnaR together with GlnR to the nirB promoter was observed, suggesting that NnaR may act as a GlnR co-activator. PMID- 22301912 TI - Adherence and associated virulence gene expression in acid-treated Escherichia coli O157 : H7 in vitro and in ligated pig intestine. AB - Escherichia coli O157 : H7 cells that interact with intestinal epithelial cells in animals and humans do so after passage through the low pH of the stomach. This study compared adherence and its associated virulence gene expression in acid treated (AT) and non-acid treated (NAT) E. coli O157 : H7 strain 86-24 in vitro and in ligated pig intestine. It was found that in vitro, AT O157 : H7 had significantly decreased adherence accompanied by decreased expression of stcE and toxB but not of the locus of enterocyte effacement (LEE) genes. Expression of gadE, genes involved in quorum sensing, and the global regulators cyaA, hfq, lrp, fis and himA was significantly increased; notably, ureD expression was increased 29-fold compared with NAT O157 : H7. AT O157 : H7 colonized the pig intestine as effectively as NAT O157 : H7 bacteria. Expression of 70 of 72 virulence genes from bacteria recovered from the intestine was similar between AT and NAT O157 : H7, except ureD, pagC and bax, whose level of expression was reduced in the AT bacteria. Genes involved in acid response, regulators gadE, cyaA and hfq, and toxin synthesis genes (stx2A and stx2B) were expressed at significantly reduced levels in the intestine by both AT and NAT strains. Expression in the intestine of the LEE and putative adhesion factors cahA, iha and lpf2 was at levels similar to those in vitro, while ehaA and ureD in NAT O157 : H7 were expressed significantly more highly in vivo than in vitro. These data indicate that AT and NAT O157 : H7 behave differently, and that expression of their virulence genes is regulated differently in vitro from in vivo. PMID- 22301913 TI - Mass screening of newborns for congenital hypothyroidism of central origin by free thyroxine measurement of blood samples on filter paper. AB - OBJECTIVE: To evaluate the effectiveness of mass screening of newborns for congenital hypothyroidism of central origin (CH-C) by measurement of free thyroxine (FT(4)) and thyroid-stimulating hormone (TSH). DESIGN: Questionnaire based survey of CH-C patients born between 1999 and 2008 in Kanagawa prefecture, Japan. METHODS: TSH and FT(4) levels in dried blood spots on filter paper were measured using ELISA kits, and CH-C was diagnosed at FT(4) levels below a cutoff of 0.7 ng/dl (9.0 pmol/l). Survey results were collated with the database created by the screening organizer. RESULTS: Twenty-four CH-C patients (18 males) were identified, 14 of whom had multiple pituitary hormone deficiencies (group M), eight had isolated CH-C (group I), and two had undetermined pituitary involvement (group U). In groups M, I, and U, the number of patients with FT(4) levels below the cutoff value at screening was five (36%), seven (88%), and one (50%) respectively; other patients had been diagnosed clinically. Thus, 13 patients were true positives, while nine were false negatives, yielding screening sensitivity of 59.1% and positive predictive value of 11.5%. The calculated sensitivity was 81.8% at a higher cutoff value of 0.9 ng/dl (11.6 pmol/l). The overall incidence of CH-C was estimated at 1 in 30, 833 live births, while that of CH of thyroidal origin (CH-T) is 1 in 3472 live births in Kanagawa prefecture (CH-T/CH-C, 8.9). CONCLUSIONS: Newborn screening with combined FT(4) and TSH measurements can identify a significant number of CH-C patients before manifestation of clinical symptoms, but a more appropriate FT(4) cutoff value should be considered. PMID- 22301914 TI - Evidence for association between paraoxonase 1 gene polymorphisms and polycystic ovarian syndrome in southwest Chinese women. AB - OBJECTIVE: The aim of this study was to investigate the relationship between 192Q/R and 55L/M polymorphisms of paraoxonase 1 (PON1) gene and polycystic ovarian syndrome (PCOS) in Chinese women. DESIGN: A case-control study. METHODS: A total of 1113 subjects (610 patients with PCOS and 503 control women) from a population of Chinese Han nationality in Chengdu area were included in this study. PON1 genotypes were studied using PCR and restriction fragment length polymorphism analysis. Clinical and metabolic parameters were analyzed. RESULTS: The frequencies of PON1 192RR genotype and R allele were significantly higher in patients with PCOS than in control women (44.6 vs 36.4%, 0.667 vs 0.610 respectively). The 192RR genotype remained a significant predictor for PCOS (odds ratio (RR/QR)(+)(QQ): 1.656, 95% confidence interval: 1.156-2.371) in prognostic models including age, body mass index, insulin resistance index, triglyceride, HDL, and LDL as covariates. Compared with patients with QQ genotype, patients with RR or QR genotype had significantly higher waist circumference and fasting insulin and triglyceride levels, patients with RR genotype had significantly higher waist-to-hip ratio, and patients with QR genotype had significantly higher homeostasis model assessment of insulin resistance. Such relationships were not detected in the control women. No significant differences were found in the frequencies of PON1 55L/M genotype and allele between PCOS and control groups. CONCLUSIONS: The 192Q/R, but not 55L/M, polymorphism in PON1 gene is associated with the risk of PCOS in south-west Chinese women. PMID- 22301915 TI - Outcomes of transsphenoidal surgery in prolactinomas: improvement of hormonal control in dopamine agonist-resistant patients. AB - CONTEXT: Few studies have recently re-examined the efficacy of neurosurgery in prolactinoma patients operated for various indications. OBJECTIVE: To analyze outcomes of patients with a prolactinoma treated by transsphenoidal surgery, to identify factors associated with remission and relapse, and to evaluate if surgical debulking allows for better hormonal control in patients with preoperative resistance to dopamine agonists (DAs). PATIENTS AND METHODS: This was a retrospective review of patients with a benign prolactinoma followed preoperatively and postoperatively in our department and treated by transsphenoidal surgery (n=63; 45 women; mean age: 31 +/- 14 years). RESULTS: Postoperative remission was obtained in 63% of microprolactinomas, 60% of noninvasive macroprolactinomas, and none of the invasive macroprolactinomas. Better remission rate was independently predicted by lower diagnostic prolactin (PRL) levels and by the lack of abnormal postoperative residual tissue (P<0.05). A recurrence of hyperprolactinemia was observed in 34% of patients after a median follow-up period of 36 (7-164) months. In patients with preoperative DA resistance treated again after surgery, there was a significant reduction in PRL levels postoperatively (26 (6-687) ng/ml) vs preoperatively (70 (22-1514) ng/ml; P<0.01) under a lower DA dose, and about half of the patients had PRL normalization. CONCLUSIONS: Recurrence of hyperprolactinemia is observed in one third of prolactinoma patients after surgical remission and may occur as late as 13 years after surgery. Resistance to DA can be considered as a good surgical indication, as partial tumor resection allows for better hormonal control with a lower dose of DAs. PMID- 22301916 TI - Genetic analysis of mitochondrial protein misfolding in Drosophila melanogaster. AB - Protein misfolding has a key role in several neurological disorders including Parkinson's disease. Although a clear mechanism for such proteinopathic diseases is well established when aggregated proteins accumulate in the cytosol, cell nucleus, endoplasmic reticulum and extracellular space, little is known about the role of protein aggregation in the mitochondria. Here we show that mutations in both human and fly PINK1 result in higher levels of misfolded components of respiratory complexes and increase in markers of the mitochondrial unfolded protein response. Through the development of a genetic model of mitochondrial protein misfolding employing Drosophila melanogaster, we show that the in vivo accumulation of an unfolded protein in mitochondria results in the activation of AMP-activated protein kinase-dependent autophagy and phenocopies of pink1 and parkin mutants. Parkin expression acts to clear mitochondria with enhanced levels of misfolded proteins by promoting their autophagic degradation in vivo, and refractory to Sigma P (ref(2)P), the Drosophila orthologue of mammalian p62, is a critical downstream effector of this quality control pathway. We show that in flies, a pathway involving pink1, parkin and ref(2)P has a role in the maintenance of a viable pool of cellular mitochondria by promoting organellar quality control. PMID- 22301917 TI - Phosphorylation of EBP50 negatively regulates beta-PIX-dependent Rac1 activity in anoikis. AB - We demonstrated a protein kinase C (PKC)-dependent phosphorylation of canine ezrin/radixin/moesin (ERM)-binding phosphoprotein 50 (EBP50) at serine 347/348 by site-directed mutagenesis and a phospho-specific antibody. Cell fractionation and confocal imaging revealed the relocation of EBP50 from the plasma membrane to cytosol that accompanied this phosphorylation event. Increased phosphorylation at these serine residues led to the dissociation of EBP50 from ezrin and beta-PIX, which are two upstream regulators of Rac1 activation. Cells overexpressing an EBP50 mutant, mimicking serine 347/348 phosphorylation, became refractory to hepatocyte growth factor-induced cell spreading and scattering, which is normally mediated by Rac1 activation. Detachment of cells from the substratum also elicited an increase in EBP50 phosphorylation, apparently due to counteracting activities of PKC and protein phosphastase 2A, which resulted in decreased Rac1 activation and induction of anoikis. Cells overexpressing an EBP50 mutant defective in serine 347/348 phosphorylation did not undergo apoptosis in suspension culture. These studies reveal a signaling cascade in which different phosphorylation states and subcellular localization of EBP50 regulate Rac1 function. PMID- 22301918 TI - Back to Stockholm for 'metabolism, epigenetics and cell death'. PMID- 22301919 TI - Suppression of Ras/Mapk pathway signaling inhibits Myc-induced lymphomagenesis. AB - Although the Myc transcription factor has been shown necessary for the oncogenic function of Ras, the contribution of Ras pathway signaling to the oncogenic function of Myc remains unresolved. We report the novel findings that Myc alone induced Ras/Mapk pathway signaling, and increased signaling following growth factor stimulation. Deletion of the scaffold protein kinase suppressor of Ras 1 (Ksr1) attenuated signaling through the Ras/Mapk pathway, including activation following Myc induction. B cells that lacked Ksr1 exhibited reduced proliferation and increased cytokine deprivation-induced apoptosis. Overexpression of Myc rescued the proliferation defect of Ksr1-null B cells, but loss of Ksr1 increased sensitivity of B cells to Myc-induced apoptosis. Notably, there was a significant delay in lymphoma development in Ksr1-null mice overexpressing Myc in B cells (EMU-myc transgenic mice). There was an elevated frequency of p53 inactivation, indicative of increased selective pressure to bypass the p53 tumor suppressor pathway, in Ksr1-null EMU-myc lymphomas. Therefore, loss of Ksr1 inhibits Ras/Mapk pathway signaling leading to increased Myc-induced B-cell apoptosis, and this results in reduced B-cell transformation and lymphoma development. Our data indicate that suppression of Myc-induced Ras/Mapk pathway signaling significantly impairs Myc oncogenic function. These results fill a significant gap in knowledge about Myc and should open new avenues of therapeutic intervention for Myc overexpressing malignancies. PMID- 22301920 TI - HDAC5 is required for maintenance of pericentric heterochromatin, and controls cell-cycle progression and survival of human cancer cells. AB - Histone deacetylases (HDACs) form a family of enzymes, which have fundamental roles in the epigenetic regulation of gene expression and contribute to the growth, differentiation, and apoptosis of cancer cells. In this study, we further investigated the biological function of HDAC5 in cancer cells. We found HDAC5 is associated with actively replicating pericentric heterochromatin during late S phase. We demonstrated that specific depletion of HDAC5 by RNA interference resulted in profound changes in the heterochromatin structure and slowed down ongoing replication forks. This defect in heterochromatin maintenance and assembly are sensed by DNA damage checkpoint pathways, which triggered cancer cells to autophagy and apoptosis, and arrested their growth both in vitro and in vivo. Finally, we also demonstrated that HDAC5 depletion led to enhanced sensitivity of DNA to DNA-damaging agents, suggesting that heterochromatin de condensation induced by histone HDAC5 silencing may enhance the efficacy of cytotoxic agents that act by targeting DNA in vitro. Together, these results highlighted for the first time an unrecognized link between HDAC5 and the maintenance/assembly of heterochromatin structure, and demonstrated that its specific inhibition might contribute to increase the efficacy of DNA alteration based cancer therapies in clinic. PMID- 22301921 TI - Resveratrol inhibits proliferation and induces apoptosis through the hedgehog signaling pathway in pancreatic cancer cell. AB - PURPOSE: To investigate the effect and possible mechanisms of resveratrol on pancreatic cancer cells in vitro. METHODS: After being treated with resveratrol, cell viability, cell cycle phase distribution and apoptosis rate of pancreatic cancer cells were measured by CCK-8 assay and flow cytometer, respectively. The effects of resveratrol on the Hedgehog pathway were studied by real-time RT-PCR and Western blotting. By interfering Gli1 expression in PANC-1 cells and overexpressing Gli1 in BxPC-3 cells, we detected the expressions of Gli1-targeted genes, such as Ptc1, CCND1 and BCL-2, compared with resveratrol experimental group. We further used the luciferase reporter assay to explore the correlation between resveratrol and Gli1. RESULTS: Resveratrol inhibited the growth of pancreatic cancer cells in a dose- and time-dependent manner. Compared with control group, the cells in the G0/G1 phase and the apoptosis rate were significantly increased. Low concentration of resveratrol decreased the expression of the Hedgehog pathway members including Gli1, Ptc1 and Smo. The expression of downstream target genes of the Hedgehog pathway such as Gli1, Ptc1, CCND1 and BCL-2 were significantly decreased after 12.5 MUM resveratrol treatment, which demonstrated a similar change of gene expression when Gli1 was knocked down by the RNAi technique in PANC-1 cells. Resveratrol also downregulated the expression of Gli1, Ptc1, CCND1 and BCL-2 in Gli1-overexpressed BxPC-3 cells. Results of the luciferase assay showed that resveratrol did not act on the Gli1 promoter directly. CONCLUSION: Resveratrol can inhibit pancreatic cancer cell survival and its mechanisms might be partly via the Hedgehog signaling pathway. and IAP. PMID- 22301923 TI - Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials. AB - BACKGROUND: There is substantial interest in chocolate and flavan-3-ols for the prevention of cardiovascular disease (CVD). OBJECTIVE: The objective was to systematically review the effects of chocolate, cocoa, and flavan-3-ols on major CVD risk factors. DESIGN: We searched Medline, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) of chocolate, cocoa, or flavan-3-ols. We contacted authors for additional data and conducted duplicate assessment of study inclusion, data extraction, validity, and random-effects meta-analyses. RESULTS: We included 42 acute or short-term chronic (<=18 wk) RCTs that comprised 1297 participants. Insulin resistance (HOMA-IR: -0.67; 95% CI: -0.98, -0.36) was improved by chocolate or cocoa due to significant reductions in serum insulin. Flow-mediated dilatation (FMD) improved after chronic (1.34%; 95% CI: 1.00%, 1.68%) and acute (3.19%; 95% CI: 2.04%, 4.33%) intakes. Effects on HOMA-IR and FMD remained stable to sensitivity analyses. We observed reductions in diastolic blood pressure (BP; -1.60 mm Hg; 95% CI: -2.77, -0.43 mm Hg) and mean arterial pressure (-1.64 mm Hg; 95% CI: -3.27, -0.01 mm Hg) and marginally significant effects on LDL (-0.07 mmol/L; 95% CI: -0.13, 0.00 mmol/L) and HDL (0.03 mmol/L; 95% CI: 0.00, 0.06 mmol/L) cholesterol. Chocolate or cocoa improved FMD regardless of the dose consumed, whereas doses >50 mg epicatechin/d resulted in greater effects on systolic and diastolic BP. GRADE (Grading of Recommendations, Assessment, Development and Evaluation, a tool to assess quality of evidence and strength of recommendations) suggested low- to moderate-quality evidence of beneficial effects, with no suggestion of negative effects. The strength of evidence was lowered due to unclear reporting for allocation concealment, dropouts, missing data on outcomes, and heterogeneity in biomarker results in some studies. CONCLUSIONS: We found consistent acute and chronic benefits of chocolate or cocoa on FMD and previously unreported promising effects on insulin and HOMA-IR. Larger, longer-duration, and independently funded trials are required to confirm the potential cardiovascular benefits of cocoa flavan-3-ols. PMID- 22301922 TI - Measuring alcohol consumption for genomic meta-analyses of alcohol intake: opportunities and challenges. AB - Whereas moderate drinking may have health benefits, excessive alcohol consumption causes many important acute and chronic diseases and is the third leading contributor to preventable death in the United States. Twin studies suggest that alcohol-consumption patterns are heritable (50%); however, multiple genetic variants of modest effect size are likely to contribute to this heritable variation. Genome-wide association studies provide a tool for discovering genetic loci that contribute to variations in alcohol consumption. Opportunities exist to identify susceptibility loci with modest effect by meta-analyzing together multiple studies. However, existing studies assessed many different aspects of alcohol use, such as typical compared with heavy drinking, and these different assessments can be difficult to reconcile. In addition, many studies lack the ability to distinguish between lifetime and recent abstention or to assess the pattern of drinking during the week, and a variety of such concerns surround the appropriateness of developing a common summary measure of alcohol intake. Combining such measures of alcohol intake can cause heterogeneity and exposure misclassification, cause a reduction in power, and affect the magnitude of genetic association signals. In this review, we discuss the challenges associated with harmonizing alcohol-consumption data from studies with widely different assessment instruments, with a particular focus on large-scale genetic studies. PMID- 22301924 TI - Percentage of body fat cutoffs by sex, age, and race-ethnicity in the US adult population from NHANES 1999-2004. AB - BACKGROUND: To date, there is no consensus regarding adult cutoffs of percentage of body fat or estimated cutoffs on the basis of nationally representative samples with rigorous body-composition measurements. OBJECTIVE: We developed cutoffs of percentage of body fat on the basis of the relation between dual energy x-ray absorptiometry-measured fat mass and BMI (in kg/m(2)) stratified by sex, age, and race-ethnicity by using 1999-2004 NHANES data. DESIGN: A simple regression (percentage of body fat = beta(0) + beta(1) * 1 / BMI) was fit for each combination of sex (men and women), 3 age groups (18-29, 30-49, and 50-84 y of age), and 3 race-ethnicity groups (non-Hispanic whites, non-Hispanic blacks, and Mexican Americans). Model fitting included a consideration of complex survey design and multiple imputations. Cutoffs of percentage of body fat were computed that corresponded to BMI cutoffs of 18.5, 25, 30, 35, and 40 on the basis of estimated prediction equations. RESULTS: R(2) ranged from 0.54 to 0.72 for men (n = 6544) and 0.58 to 0.79 for women (n = 6362). In men, the percentage of body fat that corresponded to a BMI of 18.5, 25, 30, 35, and 40 across age and racial ethnic groups ranged from 12.2% to 19.0%, 22.6% to 28.0%, 27.5% to 32.3%, 31.0% to 35.3%, and 33.6% to 37.6%, respectively; the corresponding ranges in women were from 24.6% to 32.3%, 35.0% to 40.2%, 39.9% to 44.1%, 43.4% to 47.1%, and 46.1% to 49.4%, respectively. The oldest age group had the highest cutoffs of percentage of body fat. Non-Hispanic blacks had the lowest cutoffs of percentage of body fat. Cutoffs of percentage of body fat were higher in women than in men. CONCLUSIONS: Cutoffs of percentage of body fat that correspond to the current US BMI cutoffs are a function of sex, age, and race-ethnicity. These factors should be taken into account when considering the appropriateness of levels of percentage of body fat. PMID- 22301925 TI - Equol status and blood lipid profile in hyperlipidemia after consumption of diets containing soy foods. AB - BACKGROUND: Recent analyses have challenged the effectiveness of soy foods as part of a cardiovascular risk reduction diet. OBJECTIVE: The objective of the study was to show whether equol status determines the effectiveness of soy foods to lower LDL cholesterol and to raise HDL cholesterol. DESIGN: Eighty-five hypercholesterolemic men and postmenopausal women (42 men, 43 women) participated in 1 of 3 studies that represented a range of soy interventions and that followed the same general protocol at a Canadian university hospital research center. Soy foods were provided for 1 mo at doses of 30-52 g/d for the 3 studies as follows: 1) soy foods with either high-normal (73 mg/d) or low (10 mg/d) isoflavones, 2) soy foods with or without a prebiotic to enhance colonic fermentation (10 g polyfructans/d), or 3) soy foods with a low-carbohydrate diet (26% carbohydrate). Studies 1 and 2 were randomized controlled crossover trials, and study 3 was a parallel study. RESULTS: The separation of the group into equol producers (n = 30) and nonproducers (n = 55) showed similar reductions from baseline in LDL cholesterol (-9.3 +/- 2.5% and -11.1 +/- 1.6%, respectively; P = 0.834), with preservation of HDL cholesterol and apolipoprotein A-I only in equol producers compared with reductions in nonproducers (HDL cholesterol: +0.9 +/- 2.7% compared with -4.3 +/- 1.1%, P = 0.006; apolipoprotein A-I: -1.0 +/- 1.1% compared with 4.7 +/- 1.0%; P = 0.011). The amount of urinary equol excreted did not relate to the changes in blood lipids. CONCLUSIONS: Soy foods reduced serum LDL cholesterol equally in both equol producers and nonproducers. However, in equol producers, ~35% of our study population, soy consumption had the added cardiovascular benefit of maintaining higher HDL-cholesterol concentrations than those seen in equol nonproducers. This trial was registered at clinicaltrials.gov as NCT00877825 (study 1), NCT00516594 (study 2), and NCT00256516 (study 3). PMID- 22301926 TI - Longitudinal trends in diet and effects of sex, race, and education on dietary quality score change: the Coronary Artery Risk Development in Young Adults study. AB - BACKGROUND: The food supply and dietary preferences have changed in recent decades. OBJECTIVE: We studied time- and age-related individual and population wide changes in a dietary quality score and food groups during 1985-2006. DESIGN: The Coronary Artery Risk Development in Young Adults (CARDIA) study of 5115 black and white men and women [aged 18-30 y at year 0 (1985-1986)] assessed diet at examinations at study years 0, 7 (1992-1993), and 20 (2005-2006). The dietary quality score, which was validated by its inverse association with cardiovascular disease risk, summed 46 food groups rated by investigators as positive or negative on the basis of hypothesized health effects. We used repeated-measures regression to estimate time-specific mean diet scores and servings per day of food groups. RESULTS: In 2652 participants with all 3 diet assessments, the mean (+/-SD) dietary quality score increased from 64.1 +/- 13.0 at year 0 to 71.1 +/- 12.6 at year 20, which was mostly attributable to increased age. However, the secular trend, which was estimated from differences of dietary quality scores across time at a fixed age (age-matched time trend) decreased. The diet score was higher in whites than in blacks and in women than in men and increased with education, but demographic gaps in the score narrowed over 20 y. There tended to be increases in positively rated food groups and decreases in negatively rated food groups, which were generally similar in direction across demographic groups. CONCLUSIONS: The CARDIA study showed many age-related, desirable changes in food intake over 20 y of observation, despite a secular trend toward a lower diet quality. Nevertheless, demographic disparities in diet persist. PMID- 22301927 TI - Iron metabolism in patients with anorexia nervosa: elevated serum hepcidin concentrations in the absence of inflammation. AB - BACKGROUND: Only a few studies based on small cohorts have been carried out on iron status in anorexia nervosa (AN) patients. OBJECTIVE: The aim of this study was to evaluate the role of hepcidin in hyperferritinemia in AN adolescents. DESIGN: Twenty-seven adolescents hospitalized for AN in the pediatric inpatient unit of Ambroise Pare Academic Hospital were enrolled in the study. The control group comprised 11 patients. Hematologic variables and markers of iron status, including serum hepcidin, were measured before and after nutritional rehabilitation. RESULTS: The mean age of patients was 14.4 y. Except for 2 AN patients and 1 control patient, all patients presented normal hemoglobin, vitamin B-12, and folate concentrations. Markers of inflammation and cytokines were normal throughout the study. None of the muscular lysis markers were elevated. Most AN patients had normal serum iron concentrations on admission. Serum ferritin concentrations were significantly higher in patients than in control subjects (198 compared with 49 MUg/L, respectively; P < 0.001). The median hepcidin concentration was significantly higher in AN patients than in the control group (186.5 compared with 39.5 MUg/L, respectively; P = 0.002). There was a highly significant correlation between ferritinemia and serum hepcidin concentrations (P < 0.0001). After nutritional rehabilitation, a significant reduction was observed (P = 0.004) in serum ferritin. Serum hepcidin analyzed in a smaller number of patients also returned to within the normal range. CONCLUSIONS: Hepcidin and ferritin concentrations were higher in the serum of AN patients, without any evidence of iron overload or inflammation. These concentrations returned to normal after nutritional rehabilitation. These results suggest that nutritional stress induced by malnourishment in the hepatocyte could be yet another mechanism that regulates hepcidin. PMID- 22301928 TI - Is a protein calorie better for weight control? PMID- 22301929 TI - Replacing caloric beverages with water or diet beverages for weight loss in adults: main results of the Choose Healthy Options Consciously Everyday (CHOICE) randomized clinical trial. AB - BACKGROUND: Replacement of caloric beverages with noncaloric beverages may be a simple strategy for promoting modest weight reduction; however, the effectiveness of this strategy is not known. OBJECTIVE: We compared the replacement of caloric beverages with water or diet beverages (DBs) as a method of weight loss over 6 mo in adults and attention controls (ACs). DESIGN: Overweight and obese adults [n = 318; BMI (in kg/m(2)): 36.3 +/- 5.9; 84% female; age (mean +/- SD): 42 +/- 10.7 y; 54% black] substituted noncaloric beverages (water or DBs) for caloric beverages (>=200 kcal/d) or made dietary changes of their choosing (AC) for 6 mo. RESULTS: In an intent-to-treat analysis, a significant reduction in weight and waist circumference and an improvement in systolic blood pressure were observed from 0 to 6 mo.Mean ((+/-SEM) weight losses at 6 mo were -2.5 +/- 0.45% in the DB group, -2.03 +/- 0.40% in the water group, and -1.76 +/- 0.35% in the AC group; there were no significant differences between groups [corrected]. The chance of achieving a 5% weight loss at 6 mo was greater in the DB group than in the AC group (OR: 2.29; 95% CI: 1.05, 5.01; P = 0.04). A significant reduction in fasting glucose at 6 mo (P = 0.019) and improved hydration at 3 (P = 0.0017) and 6 (P = 0.049) mo was observed in the Water group relative to the AC group. In a combined analysis, participants assigned to beverage replacement were 2 times as likely to have achieved a 5% weight loss (OR: 2.07; 95% CI: 1.02, 4.22; P = 0.04) than were the AC participants. CONCLUSIONS: Replacement of caloric beverages with noncaloric beverages as a weight-loss strategy resulted in average weight losses of 2% to 2.5%. This strategy could have public health significance and is a simple, straightforward message. This trial was registered at clinicaltrials.gov as NCT01017783. PMID- 22301930 TI - Effect of breastfeeding compared with formula feeding on infant body composition: a systematic review and meta-analysis. AB - BACKGROUND: Early-life nutrition may influence later body composition. The effect of breastfeeding and formula feeding on infant body composition is uncertain. OBJECTIVE: We conducted a systematic review and meta-analysis of studies that examined body composition in healthy, term infants in relation to breastfeeding or formula feeding. DESIGN: PubMed was searched for human studies that reported the outcomes fat-free mass, fat mass, or the percentage of fat mass in breastfed and formula-fed infants. Bibliographies were hand searched, and authors were contacted for additional data. The quality of studies was assessed. Differences in outcomes between feeding groups were compared at prespecified ages by using fixed-effects analyses except when heterogeneity indicated the use of random effects analyses. RESULTS: We identified 15 studies for inclusion in the systematic review and 11 studies for inclusion in the meta-analysis. In formula fed infants, fat-free mass was higher at 3-4 mo [mean difference (95% CI): 0.13 kg (0.03, 0.23 kg)], 8-9 mo [0.29 kg (0.09, 0.49 kg)], and 12 mo [0.30 kg (0.13, 0.48 kg)], and fat mass was lower at 3-4 mo [-0.09 kg (-0.18, -0.01 kg)] and 6 mo [-0.18 kg (-0.34, -0.01 kg)] than in breastfed infants. Conversely, at 12 mo, fat mass was higher in formula-fed infants [0.29 kg (-0.03, 0.61 kg)] than in breastfed infants. CONCLUSION: Compared with breastfeeding, formula feeding is associated with altered body composition in infancy. PMID- 22301931 TI - Does acute tryptophan depletion affect peripheral serotonin metabolism in the intestine? AB - BACKGROUND: Serotonin (5-hydroxytryptamine; 5-HT), a tryptophan metabolite, plays an important regulatory role in the human central nervous system and in the gastrointestinal tract. Acute tryptophan depletion (ATD) is currently the most widely established method to investigate 5-HT metabolism. OBJECTIVE: The aim of this study was to assess the effect of an acute decrease in the systemic availability of tryptophan on intestinal 5-HT metabolism and permeability. DESIGN: Thirty-three healthy volunteers (17 with ATD, 3 of whom dropped out; 16 placebo) participated in this randomized placebo-controlled study. Plasma and duodenal mucosal concentrations of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and kynurenic acid (KA) were measured by HPLC-mass spectrometry. Intestinal barrier function was assessed with a multisugar plasma test, and analysis of tight junction transcription was performed in duodenal biopsy samples obtained by gastroduodenoscopy. RESULTS: Mucosal 5-HT, 5-HIAA, and KA concentrations remained unaltered by ATD. In contrast, ATD significantly decreased plasma 5-HT (P < 0.05) and 5-HIAA (P < 0.0001) concentrations. After endoscopy, a significant increase in plasma 5-HT concentrations was observed in the placebo group (P = 0.029) compared with the ATD group. Moreover, a significant increase in plasma KA concentrations over time was found in the placebo group (P < 0.05). No changes in intestinal barrier function were observed. CONCLUSIONS: An acute decrease in precursor availability does not affect mucosal concentrations of serotonergic metabolites, in contrast with systemic concentrations. ATD alters biochemical responses to acute stress from the endoscopic examination reflected by lower 5-HT concentrations. Changes in 5-HT concentrations were paralleled by alterations in KA concentrations, which suggest competition between the 2 metabolic pathways for the mutual precursor. This trial was registered at clinicaltrials.gov as NCT00731003. PMID- 22301932 TI - Determinants of urinary methylmalonic acid concentration in an elderly population in the United Kingdom. AB - BACKGROUND: An age-related deterioration of vitamin B-12 status has been well documented. The early detection of deficiency may prevent the development of serious clinical symptoms, but plasma vitamin B-12 concentration is known to be an imperfect measure of vitamin B-12 status. Urinary methylmalonic acid (MMA) may be a more informative biomarker of vitamin B-12 status; however, biochemical, dietary, and other lifestyle determinants are not known. OBJECTIVE: We identified determinants of urinary MMA concentrations in free-living men and women aged >=65 y in the United Kingdom. DESIGN: A cross-sectional study in 591 men and women aged 65-85 y, with no clinical evidence of vitamin B-12 deficiency, was conducted to determine the demographic, clinical, and lifestyle determinants of urinary MMA concentration expressed as the ratio of micromoles of MMA to millimoles of creatinine (uMMA ratio). RESULTS: Twenty percent of subjects had plasma vitamin B 12 concentrations <200 pmol/L. Seventeen percent of the variation in the uMMA ratio could be explained by plasma holotranscobalamin and sex; total vitamin B-12 intake and measures of renal function and gastric function made only a small contribution to the model. The uMMA ratio was lower in people with moderately impaired renal function. CONCLUSIONS: Plasma holotranscobalamin and sex were the most important determinants of uMMA ratio in elderly people with no clinical diagnosis of renal impairment. This biomarker might underestimate vitamin B-12 deficiency in a population in which renal impairment is prevalent. This trial was registered at www.controlled-trials.com as ISRCJN83921062. PMID- 22301933 TI - Effect of increasing protein content of human milk fortifier on growth in preterm infants born at <31 wk gestation: a randomized controlled trial. AB - BACKGROUND: Preterm human milk-fed infants often experience suboptimal growth despite the use of human milk fortifier (HMF). The extra protein supplied in fortifiers may be inadequate to meet dietary protein requirements for preterm infants. OBJECTIVE: We assessed the effect of human milk fortified with a higher protein HMF on growth in preterm infants. DESIGN: This is a randomized controlled trial in 92 preterm infants born at <31 wk gestation who received maternal breast milk that was fortified with HMF containing 1.4 g protein/100 mL (higher-protein group) or 1.0 g protein/100 mL (current practice) until discharge or estimated due date, whichever came first. The HMFs used were isocaloric and differed only in the amount of protein or carbohydrate. Length, weight, and head-circumference gains were assessed over the study duration. RESULTS: Length gains did not differ between the higher- and standard-protein groups (mean difference: 0.06 cm/wk; 95% CI: -0.01, 0.12 cm/wk; P = 0.08). Infants in the higher-protein group achieved a greater weight at study end (mean difference: 220 g; 95% CI: 23, 419 g; P = 0.03). Secondary analyses showed a significant reduction in the proportion of infants who were less than the 10th percentile for length at the study end in the higher-protein group (risk difference: 0.186; 95% CI: 0.370, 0.003; P = 0.047). CONCLUSIONS: A higher protein intake results in less growth faltering in human milk-fed preterm infants. It is possible that a higher-protein fortifier than used in this study is needed. This trial was registered with the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au/) as ACTRN12606000525583. PMID- 22301934 TI - An innovative approach to measure compliance to a gluten-free diet. PMID- 22301935 TI - Association of TMPRSS6 polymorphisms with ferritin, hemoglobin, and type 2 diabetes risk in a Chinese Han population. AB - BACKGROUND: Transmembrane protease serine 6 (TMPRSS6) regulates iron homeostasis by inhibiting the expression of hepcidin. Multiple common variants in TMPRSS6 were significantly associated with serum iron in recent genome-wide association studies, but their effects in the Chinese remain to be elucidated. OBJECTIVE: The objective was to determine whether the TMPRSS6 single nucleotide polymorphisms (SNPs) rs855791(V736A) and rs4820268(D521D) were associated with blood hemoglobin and plasma ferritin concentrations and risk of type 2 diabetes in Chinese individuals. DESIGN: The SNPs rs855791(V736A) and rs4820268(D521D) in the TMPRSS6 gene were genotyped and tested for their associations with plasma iron and type 2 diabetes risk in 1574 unrelated Chinese Hans from Beijing. RESULTS: The 2 TMPRSS6 SNPs rs855791(V736A) and rs4820268(D521D) were both significantly associated with plasma ferritin (P <= 0.0058), hemoglobin (P <= 0.0013), iron overload risk (P <= 0.0068), and type 2 diabetes risk (P <= 0.0314). None of the associations with hemoglobin or plasma ferritin remained significant (P >= 0.1229) when the 2 variants were both included in one linear regression model. A haplotype carrying both iron-lowering alleles from the 2 TMPRSS SNPs showed significant associations with lower hemoglobin (P = 0.0014), lower plasma ferritin (P = 0.0027), and a reduced risk of iron overload (P = 0.0017) and of type 2 diabetes (P = 0.0277). CONCLUSIONS: These findings suggest that TMPRSS6 variants were significantly associated with plasma ferritin, hemoglobin, risk of iron overload, and type 2 diabetes in Chinese Hans. The type 2 diabetes risk conferred by the TMPRSS6 SNPs is possibly mediated by plasma ferritin. PMID- 22301936 TI - Relation between holiday weight gain and total energy expenditure among 40- to 69 y-old men and women (OPEN study). AB - BACKGROUND: A significant proportion of the average annual body weight (BW) gain in US adults (~0.5-1 kg/y) may result from modest episodes of positive energy balance during the winter holiday season. OBJECTIVE: We tested whether holiday BW gain was reduced in participants with high baseline total energy expenditure (TEE) or whether it varied by BMI (in kg/m(2)). DESIGN: In a secondary analysis of previously published data, DeltaBW normalized over 90 d from mid-September/mid October 1999 to mid-January/early March 2000 was analyzed by sex, age, and BMI in 443 men and women (40-69 y of age). TEE was measured by doubly labeled water. High or low energy expenditure was assessed as residual TEE after linear adjustment for age, height, and BW. RESULTS: No correlations between DeltaBW and TEE or TEE residuals were found. Sixty-five percent of men and 58% of women gained >=0.5 kg BW, with ~50% of both groups gaining >=1% of preholiday BW. Obese men (BMI >=30) gained more BW than did obese women. CONCLUSIONS: A high preholiday absolute TEE or residual TEE did not protect against BW gain during the winter holiday quarter. It is not known whether higher than these typical TEE levels would protect against weight gain or if the observed gain may be attributed to increased food consumption and/or reduced physical activity during the holiday quarter. PMID- 22301937 TI - Formation of gold nanorods by a stochastic "popcorn" mechanism. AB - Gold nanorods have significant technological potential and are of broad interest to the nanotechnology community. The discovery of the seeded, wet-chemical synthetic process to produce them may be regarded as a landmark in the control of metal nanoparticle shape. However, the mechanism by which the initial spherical gold seeds acquire anisotropy is a critical, yet poorly understood, factor. Here we examine the very early stages of rod growth using a combination of techniques including cryogenic transmission electron microscopy, optical spectroscopy, and computational modeling. Reconciliation of the available experimental observations can only be achieved by invoking a stochastic, "popcorn"-like mechanism of growth, in which individual seeds lie quiescent for some time before suddenly and rapidly growing into rods. This is quite different from the steady, concurrent growth of nanorods that has been previously generally assumed. Furthermore we propose that the shape is controlled by the ratio of surface energy of rod sides to rod ends, with values of this quantity in the range of 0.3-0.8 indicated for typical growth solutions. PMID- 22301938 TI - Effect of the alpha-glucosidase inhibitor miglitol on the glucose profile in Japanese type 2 diabetic patients receiving multiple daily insulin injections. AB - Strict postprandial glycemic control may have a preventive effect on atherogenesis in patients with type 2 diabetes. The alpha-glucosidase inhibitor (alpha-GI) miglitol is useful for controlling the early postprandial increase of glucose, but the combined effect of miglitol and multiple daily insulin injections (MDI) on glucose excursion has not been evaluated. First, we retrospectively compared the daily glucose profile, evaluated by self-monitoring of blood glucose (SMBG) at nine times on the day before discharge from hospital, between type 2 diabetic patients receiving MDI (n=81) or MDI plus miglitol at 150 mg daily (n=24). Second, we prospectively examined the effect of adding miglitol to MDI on the daily glucose profile (SMBG) in 19 other type 2 diabetic patients. Although the daily insulin dosage and the glucose level before meals did not differ between the two groups, the 1-h postprandial glucose level after each meal, 2-h glucose level after lunch and dinner, mean and standard deviation of glucose, and amplitude of glucose excursion were significantly lower or smaller in the MDI plus miglitol group than in the MDI group. All of these glucose parameters were significantly improved by adding miglitol to MDI in the prospective cohort of 19 patients. In conclusion, adding miglitol to MDI reduces postprandial glucose levels and attenuates daily glucose fluctuation in type 2 diabetic patients. This trial was registered with UMIN (no. UMIN000005383). PMID- 22301939 TI - Potential correlation between plasma total GIP levels and body mass index in Japanese patients with types 1 or 2 diabetes mellitus. AB - Glucose-dependent insulinotropic polypeptide (GIP) secretion in diabetic Europeans with type 1 (T1DM) and type 2 (T2DM) following test meal (TM) has been shown to be normal. In Japanese patients with T2DM, GIP secretion was also normal. We determined whether GIP secretin is influenced by various factors. Plasma glucose (PG), serum insulin (s-IRI), serum C-peptide (s-CPR), and plasma total GIP (p-total GIP) levels were measured at 0, 30, and 60 minutes after TM (560 kcal) in patients with T1DM (n = 15, group 1) and T2DM (n = 29, group 2) treated with various medications. HbA1c was also measured. At baseline, means of age, BMI, HbA1c, PG, s-CPR, SUIT (secretory unit in transplantation) and p total GIP were significantly lower in group 1 than in group 2. Each mean of postprandial p-total GIP levels after TM in all patients was more dramatically increased than other factors. The area under the curve (AUC) of p-total GIP levels in early-phase (0 to 30 min) was significantly positively correlated with BMI in group 2 but not in group 1, and not with other factors. These results indicate that the GIP secretion after TM in diabetic Japanese patients was dramatically increased, and the AUC of GIP secretion in early-phase was positively correlated with BMI in non-obese and obese patients with T2DM, but not with T1DM. The increase was not influenced by gender, age, glycemic control, duration of disease, micro- or macro-vascular disturbances, or oral drugs. PMID- 22301940 TI - Spontaneous asymmetric crystallization of a quartz-type framework from achiral precursors. AB - An enantioenriched three-dimensional quartz-type framework {[Ni(1.5)(tzdc)(H(2)O)(3)].3H(2)O}(n) (H(3)tzdc = 4H-1,2,4-triazole-3,5 dicarboxylic acid) possessing chiral channels is obtained through spontaneous asymmetric crystallization without any enantiopure additive. PMID- 22301941 TI - High yield synthesis of a neutral and carbonyl-rich terminal arylborylene complex. AB - High yield synthesis of trans-[(Me(3)P)(OC)(3)Fe = BDur] (Dur, "Duryl" = 2,3,4,6 Me(4)C(6)H) is achieved by salt elimination and subsequent liberation of trimethylsilylbromide from K[Fe(CO)(3)(PMe(3))SiMe(3)] and Br(2)BDur. PMID- 22301942 TI - Acquired hemophilia A in a patient with essential thrombocythemia. AB - A 69-year-old woman with essential thrombocythemia (ET) developed giant ecchymosis, and she was admitted to hospital. Marked anemia (Hb 8.1 g/dl) accompanied by a prolonged activated partial thromboplastin time (89.6 s) was observed, and she received red blood cells (RBC) and fresh frozen plasma (FFP). On day 2 after admission, consciousness disturbance suddenly occurred, whereas computed tomography of the brain showed no evidence of bleeding. As the ecchymosis progressed, she developed shock. Although RBC and FFP transfusions were administered, she developed multi-organ failure and died 48 h after admission. Low factor VIII activity (<1%) accompanied by factor VIII inhibitor (17 Bethesda units) was found after her death. An autopsy revealed cerebral infarction without cerebral herniation. To date, acquired hemophilia A accompanying ET has been described in only one other patient. Although acquired factor VIII inhibitor is a rare disease, it should be tested for in ET patients with marked hemorrhagic tendency. PMID- 22301943 TI - Deletion of Fas protects islet beta cells from cytotoxic effects of human islet amyloid polypeptide. AB - AIMS/HYPOTHESIS: Islet amyloid, which is mainly composed of human islet amyloid polypeptide (hIAPP), is a pathological characteristic of type 2 diabetes and also forms in cultured and transplanted islets. We used islet beta cells as well as two ex vivo models of islet amyloid formation, cultured human islets and hIAPP expressing transgenic mouse islets with or without beta cell Fas deletion, to test whether: (1) the aggregation of endogenous hIAPP induces Fas upregulation in beta cells; and (2) deletion or blocking of Fas protects beta cells from amyloid toxicity. METHODS: INS-1, mouse or human islet cells were cultured with hIAPP alone, or with amyloid inhibitor or Fas antagonist. Non-transduced islets, and human islets or hIAPP-expressing mouse islets transduced with an adenovirus that delivers a human proIAPP-specific small interfering RNA (siRNA) (Ad-ProhIAPP siRNA) were cultured to form amyloid. Mouse islets expressing hIAPP with or without Fas were similarly cultured. Beta cell Fas upregulation, caspase-3 activation, apoptosis and function, and islet IL-1beta levels were assessed. RESULTS: hIAPP treatment induced Fas upregulation, caspase-3 activation and apoptosis in INS-1 and islet cells. The amyloid inhibitor or Fas antagonist reduced apoptosis in hIAPP-treated beta cells. Islet cells with Fas deletion had lower hIAPP-induced beta cell apoptosis than those expressing Fas. Ad-ProhIAPP siRNA-mediated amyloid inhibition reduced Fas upregulation and IL-1beta immunoreactivity in human and hIAPP-expressing mouse islets. Cultured hIAPP expressing mouse islets with Fas deletion had similar amyloid levels, but lower caspase-3 activation and beta cell apoptosis, and a higher islet beta:alpha cell ratio and insulin response to glucose, compared with islets expressing Fas and hIAPP. CONCLUSIONS/INTERPRETATION: The aggregation of biosynthetic hIAPP produced in islets induces beta cell apoptosis, at least partially, via Fas upregulation and the Fas-mediated apoptotic pathway. Deletion of Fas protects islet beta cells from the cytotoxic effects of endogenously secreted (and exogenously applied) hIAPP. PMID- 22301944 TI - Dual effects of statins on Abeta metabolism: upregulation of the degradation of APP-CTF and Abeta clearance. AB - BACKGROUND/AIMS: Retrospective cohort studies have suggested that statin users have a lower prevalence of dementia. On the other hand, a randomized controlled study failed to show beneficial effects on the cognitive decline in Alzheimer's disease (AD). However, a prospective cohort study demonstrated that users of statins had a lower incidence of AD. One possible interpretation might be that statins could prevent or delay the onset of AD, but not slow cognitive decline once the disease has set in. Given that statins could prevent or delay the onset of AD, what is the responsible mechanism? METHODS: We investigated the effect of fluvastatin on Abeta metabolism at a clinically relevant dose in mice. RESULTS: Fluvastatin reduced the brain Abeta level by increased trafficking of the carboxyl terminal fragment of the amyloid precursor protein (APP-CTF), which was mediated by inhibition of protein isoprenylation. Moreover, the statin reduced the brain Abeta level through enhanced Abeta clearance mediated by upregulation of low-density lipoprotein receptor-related protein 1 (LRP-1) expression. The statin increased LRP-1 expression, mediated by inhibition of protein isoprenylation. CONCLUSION: Statins might prevent the onset of AD through reduced Abeta production by enhancement of APP-CTF degradation and/or upregulation of Abeta clearance. We also showed that promotion of APP-CTF degradation and upregulation of Abeta clearance could be modified by a drug, suggesting possible mechanistic targets for disease-modifying drugs. PMID- 22301945 TI - The distribution profile and oxidation states of biometals in APP transgenic mouse brain: dyshomeostasis with age and as a function of the development of Alzheimer's disease. AB - The enrichment of transition metals in the brain and the dyshomeostasis of metals are thought to be important etiological factors for elderly people in a number of neurodegenerative diseases, including Alzheimer's disease (AD). However, the understanding of how biometals dynamically dysregulate in the stages of AD development, such as the exact time-dependent and site-dependent accumulation in the brain with AD progression, is still limited. Herein, by using the APP/V717I transgenic mouse model and age-matched mice as control, we offer distinctive in situ and quantitative images of metals (Cu, Fe, Zn and Ca) in brain sections by synchrotron radiation micro beam X-ray fluorescence (SR-MUXRF). The images show that Fe and Ca increased with brain aging in both AD and control (CNT) mice, and Cu, Fe, Zn and Ca appeared significantly elevated in AD mice and showed an obvious age-dependent rise. Fe, Cu and Zn were obviously specifically enriched in the cortex and hippocampus, which were also the plaque-formation sensitive brain regions. Our results demonstrate that the enrichment of transition metals with age and metals' dyshomeostasis in specific regions may contribute together to the etiology and development of AD in elderly people. The XANES measurements of Cu and Fe show evidence that Cu may have redox properties in the AD brain. PMID- 22301947 TI - The effect of pre-existing maternal obesity on the placental proteome: two dimensional difference gel electrophoresis coupled with mass spectrometry. AB - Our aim was to study the protein expression profiles of placenta obtained from lean and obese pregnant women with normal glucose tolerance at the time of term Caesarean section. We used two-dimensional difference gel electrophoresis (2D DIGE), utilising narrow-range immobilised pH gradient strips that encompassed the broad pH range of 4-5 and 5-6, followed by MALDI-TOF mass spectrometry of selected protein spots. Western blot and quantitative RT-PCR (qRT-PCR) analyses were performed to validate representative findings from the 2D-DIGE analysis. Eight proteins were altered (six down-regulated and two up-regulated on obese placentas). Annexin A5 (ANXA5), ATP synthase subunit beta, mitochondria (ATPB), brain acid soluble protein 1 (BASP1), ferritin light chain (FTL), heterogeneous nuclear ribonucleoprotein C (HNRPC) and vimentin (VIME) were all lower in obese patients. Alpha-1-antitrypsin (A1AT) and stress-70 protein, mitochondrial (GRP75) were higher in obese patients. Western blot analysis of ANXA5, ATPB, FTL, VIME, A1AT and GRP75 confirmed the findings from the 2D-DIGE analysis. For brain acid soluble protein 1 and HNRPC, qRT-PCR analysis also confirmed the findings from the 2D-DIGE analysis. Immunohistochemical analysis was also used to determine the localisation of the proteins in human placenta. In conclusion, proteomic analysis of placenta reveals differential expression of several proteins in patients with pre-existing obesity. These proteins are implicated in a variety of cellular functions such as regulation of growth, cytoskeletal structure, oxidative stress, inflammation, coagulation and apoptosis. These disturbances may have significant implications for fetal growth and development. PMID- 22301948 TI - Reduction of acute hepatic damage induced by acetaminophen after treatment with diphenyl diselenide in mice. AB - In this study, the authors evaluated the ability of diphenyl diselenide (PhSe)(2) to reverse acute hepatic failure induced by acetaminophen (APAP) in mice. The animals received an APAP dose of 600 mg/kg intraperitoneally (i.p.), and then 1 hour later, they received 15.6 mg/kg i.p. of (PhSe)(2). Three hours after (PhSe)(2) administration, the animals were sacrificed and blood and liver samples were collected for analysis. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. The levels of reduced glutathione (GSH) and oxidized glutathione (GSSG), thiobarbituric acid-reactive substances (TBARS), 2',7'-dichlorofluorescein (DFC), catalase activity (CAT), and myeloperoxidase (MPO) activity were determined in the liver. A methyl-tetrazolium reduction (MTT) assay was also performed on the liver. Histopathological studies were conducted in all groups. Exposure of animals to APAP induced oxidative stress, increased lipid peroxidation (LPO), and the generation of reactive species, reduced the levels of GSH, and caused an increase in the MPO activity. Treatment with (PhSe)(2) reduced LPO and the formation of reactive species and inhibited the processes of inflammation, reducing the hepatic damage induced by APAP. The results of this study show that (PhSe)(2) is a promising therapeutic option for the treatment of acute hepatic failure. PMID- 22301949 TI - Cytokine pathways in allergic disease. AB - Cytokines are critical in allergic intercellular communication networks, and they contribute to disease pathology through the recruitment and activation of pro inflammatory leukocytes and in chronic disease to pro-fibrotic/remodeling events. Th2 cytokines predominate primarily in mild to moderate allergic asthma, although clinical trials with inhibitors of IL-4 and IL-5 have not provided the robust efficacy observed in animal models of allergy. These results not only highlight the complexity of allergic disease, but they also point to the importance of other cytokine networks in driving pathology. The heterogeneous nature of the disease is emphasized by the fact that the Th2/Th1/Th17 cytokine balance can be influenced by the initiating allergic trigger. For example, the house dust mite allergen Der p 2 mimics the activity of MD-2 by presenting lipopolysaccharide to Toll-like receptor-4 for the activation of inflammatory genes including innate type cytokines. Here we discuss the functions of the novel cytokine players, thymic stromal lymphopoetin (TSLP), IL-33, IL-25, and IL-9 and delineate nonredundant roles for IL-4 and IL-13 in allergic disease. Persistent efforts in the characterization of these and other cytokine networks will be essential for understanding the complex pathogenic mechanisms that underpin allergic disease and for guiding targeted therapeutic interventions. PMID- 22301950 TI - The PPARalpha agonists fenofibrate and CP-778875 cause increased beta-oxidation, leading to oxidative injury in skeletal and cardiac muscle in the rat. AB - Weak peroxisome proliferator-activated receptor (PPAR) alpha agonists (fibrates) are used to treat dyslipidemia. This study compared the effects of the potent and selective PPARalpha agonist CP-778875 on peroxisomal beta-oxidation and cardiac and/or skeletal muscle injury with those of the weak PPARalpha agonist fenofibrate. We hypothesized that these muscle effects are mediated through the PPARalpha receptor, leading to increased beta-oxidation and consequent oxidative stress. CP-778875 (5 or 500 mg/kg) and fenofibrate (600 or 2,000->1,200 mg/kg, dose lowered because of intolerance) were administered to rats for six weeks. Standard end points, serum troponin I, heart and skeletal muscle beta-oxidation of palmitoyl-CoA, and acyl co-oxidase (AOX) mRNA were assessed. Both compounds dose-dependently increased the incidence and/or severity of cardiomyocyte degeneration and necrosis, heart weight, troponin I, and skeletal muscle degeneration. Mean heart beta-oxidation (3.4- to 5.1-fold control) and AOX mRNA (2.4- to 3.2-fold control) were increased with CP-778875 500 mg/kg and both doses of fenofibrate. beta-Oxidation of skeletal muscle was not affected by either compound; however, a significant increase in AOX mRNA (1.6- to 2.1-fold control) was observed with CP-778875 500 mg/kg and both doses of fenofibrate. Taken together, these findings were consistent with PPARalpha agonism and support the link between increased cardiac and skeletal muscle beta-oxidation and resultant muscle injury in the rat. PMID- 22301951 TI - Nasal passages of Gottingen minipigs from the neonatal period to young adult. AB - Histopathological examination of the nasal passages requires a standardized approach for recording lesion distribution patterns. Nasal diagrams provide guidance to map the lesions. Information on lesions exists for rodents, dogs, and monkeys, which all have been used in inhalation studies. Recently, minipigs have garnered interest as an inhalation model because minipigs resemble humans in many features of anatomy, physiology, and biochemistry and may be a good alternative to monkeys and dogs. The present work explored the microanatomy and histology of the nasal passages of Gottingen minipigs from postnatal day 1 until 6 months of age. Six nasal levels were selected, which allow examination of the squamous, transitional (nonciliated) and ciliated respiratory, and olfactory epithelia; the nasopharynx; and relevant structures such as the vomeronasal organ, olfactory bulb, and nasal/nasopharynx-associated lymphoid tissue. PMID- 22301952 TI - Biomarkers of collecting duct injury in Han-Wistar and Sprague-Dawley rats treated with N-phenylanthranilic Acid. AB - N-phenylanthranilic acid is a chloride channel blocker that causes renal papillary necrosis in rats. Studies were conducted in two strains of male rats to evaluate novel biomarkers of nephrotoxicity. Han-Wistar rats were given daily oral doses of 50, 350, or up to 700 mg/kg/day of NPAA, and Sprague-Dawley rats were given 50 or 400 mg/kg/day of NPAA. Rats were euthanized on days 8 and 15. The candidate kidney injury biomarkers renal papillary antigen-1 (RPA-1, for collecting duct injury), clusterin (for general kidney injury), alpha-glutathione S-transferase (a proximal tubular marker), and u-glutathione-S-transferase (a distal tubular marker) were measured in urine by enzyme immunoassay. Characteristic degeneration and necrosis of the collecting duct and renal papilla were observed in Han-Wistar rats at the high dose on day 8 and at the mid and high doses on day 15, and in Sprague-Dawley rats given the high dose on days 8 and 15. Increases in urinary RPA-1, and to a lesser extent urine clusterin, were generally associated with the presence of collecting duct injury and were more sensitive than BUN and serum creatinine. On the other hand, decreases in alpha glutathione-S-transferase without proximal tubule lesions in both strains and decreases in u-glutathione-S-transferase in Sprague-Dawley rats only were not associated with morphological proximal or distal tubule abnormalities, so both were of less utility. It was concluded that RPA-1 is a new biomarker with utility in the detection of collecting duct injury in papillary necrosis in male rats. PMID- 22301953 TI - Complementary treatment of siTERT for improving the antitumor effect of TERT specific I-131 therapy. AB - Sodium iodide symporter (NIS)-based radionuclide therapy provides an effective means of treating malignant tumors. However, it is sometimes inadequate because of limited effects on radio-resistant tumors, and thus, combination therapies with other therapeutic options have been requested to enhance its efficacy. Human telomerase reverse transcriptase (hTERT) has been reported to be involved in the progression of most cancers and also been viewed as a good candidate for targeting tumor. Application of TERT-specific radionuclide therapies using NIS gene transfer have been reported to treat TERT-positive tumors, but this approach only demonstrated tumor regression rather than eradication. As inhibiting TERT expression by introducing the hTERT-specific shRNA (siTERT) has been suggested as a therapeutic option, we investigated the complementary role of siTERT treatment after the TERT-specific I-131 therapy and its possibility as a novel anticancer therapeutic strategy. Retroviruses containing TERT promoter/NIS for TERT specific Radionuclide therapy and siTERT for TERT targeting antisense therapy were produced. Hep3B cells expressing TERT specific NIS (Hep3B-TERT/NIS) were xenografted into nude mouse and visualized with micro-SPECT/CT for monitoring NIS activity. The levels of hTERT mRNA, protein and its activity were confirmed by RT PCR, Western blotting and Telomerase repeat amplification protocol assay. Cell proliferation was monitored by MTT assay and induced apoptosis was confirmed by Annexin-V-PI staining. Therapeutic effects of I-131 and/or siTERT were evaluated by clonogenic assay and mouse tumor model. Reduction of hTERT mRNA, protein and TERT activity by siTERT were observed in Hep3B-TERT/NIS cells. The viabilities of the infected cells were significantly decreased to 50% versus siScramble treated controls. The early apoptotic cell population was increased by siTERT. The survival rates of cells treated with siTERT or I-131 alone were 72.4+/-7.6% and 56.2+/-5.2%, respectively. However, the survival rate of cells treated with I-131 and siTERT were decreased to 22.1+/-2.8%. From mouse xenograft model, we also found that the siTERT gene therapy showed synergism to the radioiodine therapy for reducing tumor growth in vivo. Our Results suggested that complementary siTERT gene therapy offers a novel strategy of cancer therapy to improve the therapeutic efficacy of TERT-specific I-131. PMID- 22301954 TI - MYC-driven tumorigenesis is inhibited by WRN syndrome gene deficiency. AB - MYC-induced DNA damage is exacerbated in WRN-deficient cells, leading to replication stress and accelerated cellular senescence. To determine whether WRN deficiency impairs MYC-driven tumor development, we used both xenograft and autochthonous tumor models. Conditional silencing of WRN expression in c-MYC overexpressing non-small cell lung cancer xenografts impaired both tumor establishment and tumor growth. This inhibitory effect of WRN knockdown was accompanied by increased DNA damage, decreased proliferation, and tumor necrosis. In the EMU-Myc mouse model of B-cell lymphoma, a germline mutation in the helicase domain of Wrn (Wrn(Deltahel/Deltahel)) resulted in a significant delay in emergence of lethal lymphomas, extending tumor-free survival by more than 30%. Analysis of preneoplastic B cells from EMU-Myc Wrn mutant mice revealed increased DNA damage, elevation of senescence markers, and decreased proliferation in comparison with cells from age-matched EMU-Myc mice. Immunohistochemical and global gene expression analysis of overt EMU-Myc Wrn(Deltahel/Deltahel) lymphomas showed a marked increase in expression of the CDK inhibitor, p16(Ink4a), as well as elevation of TAp63, a known mediator of senescence. Collectively, these studies show that in the context of Myc-associated tumorigenesis, loss of Wrn amplifies the DNA damage response, both in preneoplastic and neoplastic tissue, engaging activation of tumor suppressor pathways. This leads to inhibition of tumor growth and prolonged tumor-free survival. Targeting WRN or its enzymatic function could prove to be an effective strategy in the treatment of MYC associated cancers. PMID- 22301955 TI - The Charophycean green algae as model systems to study plant cell walls and other evolutionary adaptations that gave rise to land plants. AB - The Charophycean green algae (CGA) occupy a key phylogenetic position as the evolutionary grade that includes the sister group of the land plants (embryophytes), and so provide potentially valuable experimental systems to study the development and evolution of traits that were necessary for terrestrial colonization. The nature and molecular bases of such traits are still being determined, but one critical adaptation is thought to have been the evolution of a complex cell wall. Very little is known about the identity, origins and diversity of the biosynthetic machinery producing the major suites of structural polymers (i. e., cell wall polysaccharides and associated molecules) that must have been in place for land colonization. However, it has been suggested that the success of the earliest land plants was partly based on the frequency of gene duplication, and possibly whole genome duplications, during times of radical habitat changes. Orders of the CGA span early diverging taxa retaining more ancestral characters, through complex multicellular organisms with morphological characteristics resembling those of land plants. Examination of gene diversity and evolution within the CGA could help reveal when and how the molecular pathways required for synthesis of key structural polymers in land plants arose. PMID- 22301956 TI - The M. truncatula SUNN gene is expressed in vascular tissue, similarly to RDN1, consistent with the role of these nodulation regulation genes in long distance signaling. AB - Encoding a conserved protein of unknown function, the Medicago truncatula RDN1 gene is involved in autoregulation of nodulation through signaling in the root. In contrast, the SUNN kinase in M. truncatula has been shown by grafting of mutant scions to control nodule number in the root by communication of a signal from the shoot to the root. GUS staining patterns resulting from expression of the SUNN promoter fused to uidA showed expression of SUNN in most parts of plant including the root, but confined to the vascular tissue, a pattern that overlaps with that published for RDN1. Real Time qRT-PCR analysis showed levels of both SUNN RNA and RDN1 RNA did not change significantly during early nodulation signaling (0-72 hours after inoculation). The similarity in expression in cell types strongly suggests vascular signaling for nodule number regulation, while the lack of changes over early nodule development suggest post transcriptional mechanisms such as protein association or phosphorylation transmit the signal. PMID- 22301957 TI - Pollination: a key event controlling the expression of genes related to phytohormone biosynthesis during grapevine berry formation. AB - Berry formation is the process of ovary conversion into a functional fruit, and is characterized by abrupt changes in the content of several phytohormones, associated with pollination and fertilization. Much effort has been made in order to improve our understanding of berry development, particularly from veraison to post-harvest time. However, the period of berry formation has been poorly investigated, despite its importance. Phytohormones are involved in the control of fruit formation; hence it is important to understand the regulation of their content at this stage. Grapevine is an excellent fleshy-fruit plant model since its fruits have particularities that differentiate them from those of commonly studied organisms. For instance, berries are prepared to cope with stress by producing several antioxidants and they are non-climacteric fruits. Also its genome is fully sequenced, which allows to identify genes involved in developmental processes. In grapevine, no link has been established between pollination and phytohormone biosynthesis, until recently. Here we highlight relevant findings regarding pollination effect on gene expression related to phytohormone biosynthesis, and present unpublished results showing how quickly this effect is achieved. PMID- 22301958 TI - Poplar root exudates contain compounds that induce the expression of MiSSP7 in Laccaria bicolor. AB - Communication between organisms is crucial for their survival, especially for sessile organisms such as plants that depend upon interactions with mutualistic organisms to maximize their nutrient acquisition. This communication can take the form of the exchange of volatile compounds, metabolites or effectors - small protein signals secreted from the colonizing cell that change the biology of the host cell. We recently characterized the first mutualistic effector protein from an ectomycorrhizal fungus, a small secreted protein named MiSSP7 encoded by Laccaria bicolor. Ectomycorrhizal fungi are soil-borne mutualistic organisms whose hyphae wrap around host roots and grow into the root apoplastic space where the fungus exchanges nutrients such as nitrogen and phosphorus in return for plant derived sugars. The MiSSP7 protein is induced by root exudates and is highly expressed throughout the root colonization process. Its presence was responsible for alterations to the plant transcriptomic profile, a mechanism by which MiSSP7 may aid in the formation of the symbiotic interface. Here we further discuss the implications of these findings and, further, we demonstrate that the production of MiSSP7 is induced by two flavonoids, rutin and quercitrin, a class of compounds normally found within the exudates of plant roots. We also consider the interesting similarities between the mechanisms of effector induction and action between pathogenic and mutualistic fungi. PMID- 22301959 TI - Aberrant microtubule organization in dividing root cells of p60-katanin mutants. AB - Aberrant microtubule organization has been recently recorded in dividing root cells of fra2 and lue1 p60-katanin Arabidopsis thaliana mutants. Here, we report similar defects in the bot1 and ktn1-2 mutants of the same plant, proposing that they constitute a consistent phenotype of p60-katanin mutants. In addition, we show that the Targeting Protein for Xklp2 (TPX2) protein co-localizes with microtubules on the surface of prophase nuclei of the mutants, probably participating in multipolar spindle assembly. As microtubule organization defects are not observed in metaphase/anaphase spindles and initiating phragmoplasts, we also discuss the putative association of the observed aberrations with the nuclear envelope and we emphasize on the mechanism of bipolar metaphase spindle organization in the mutants. It seems that chromosome-mediated spindle assembly, probably minimally dependent on microtubule severing by p60-katanin, dominates after nuclear envelope breakdown, restoring bipolarity. PMID- 22301960 TI - Recovery from drought stress in tobacco: an active process associated with the reversal of senescence in some plant parts and the sacrifice of others. AB - Plant response to water deficit and subsequent re-watering is fine tuned at the whole plant level. It differs not only between shoot and root, but also among particular leaves along a plant axis. We estimated the expression of proline metabolism-related genes and the activity of senescence-related promoter in roots and individual leaves of tobacco plants in the course of drought stress and recovery. Proline plays the dual role of an osmoprotectant and an antioxidant under water deficit. High proline concentration in the youngest uppermost leaves contributed to their protection from drought, which was associated with low degree of senescence. During recovery, elevated proline concentrations persisted and the senescence-related promoter was switched off in all surviving leaves. Two mutually exclusive scenarios were followed by tobacco leaves on recovery- restoration of photosynthesis and metabolism, or death, depending on the progress of senescence. PMID- 22301961 TI - Expression pattern and putative function of EXL1 and homologous genes in Arabidopsis. AB - The Arabidopsis EXORDIUM-LIKE1 (EXL1) gene (At1g35140) is required for adaptation to carbon (C)- and energy-limiting growth conditions. An exl1 loss of function mutant showed diminished biomass production in a low total irradiance growth regime, impaired survival during extended night, and impaired survival of anoxia stress. We show here additional expression data and discuss the putative roles of EXL1. We hypothesize that EXL1 suppresses brassinosteroid-dependent growth and controls C allocation in the cell. In-depth expression analysis of homologous genes suggests that the EXL2 (At5g64260) and EXL4 (At5g09440) genes play similar roles. PMID- 22301962 TI - ZFP5 encodes a functionally equivalent GIS protein to control trichome initiation. AB - The Arabidopsis thaliana trichome development is a model system for understanding various aspects of plant cell development and differentiation. The C2H2 zinc finger proteins GIS, GIS2, and ZFP8 play important roles in controlling trichome initiation. In our recent study, we reported that a new C2H2 zinc finger protein, ZINC FINGER PROTEIN 5 (ZFP5), controls trichome cell development through GA signaling. ZFP5 acts upstream of GIS gene family and key trichome initiation regulators, and ZFP8 is the direct target gene of ZFP5. Here we show that ZFP5 encodes a protein functionally equivalent to GIS and GIS2 in controlling trichome initiation. Furthermore, similar to GIS2, ZFP5 is not involved in trichome branching. PMID- 22301963 TI - The Arabidopsis voltage-dependent anion channel 2 is required for plant growth. AB - The voltage-dependent anion channels (VDACs) known as a major group of outer mitochondrial membrane proteins are present in all eukaryotic species. In mammalian cells, they have been established as a key player in mitochondrial metabolism and apoptosis regulation. By contrast, little is known about the function of plant VDACs. Recently, we performed functional analysis of all VDAC gene members in Arabidopsis thaliana, and revealed that each AtVDAC member has a specialized function. Especially, in spite of similar subcellular localization and expression profiling of AtVDAC2 and AtVDAC4, both the T-DNA insertion knockout mutants of them, vdac2-2 and vdac4-2, showed severe growth retardation. These results suggest that AtVDAC2 and AtVDAC4 proteins clearly have distinct functions. Here, we introduced the AtVDAC2 gene into the vdac2-2 mutant, and demonstrated that the miniature phenotype of vdac2-2 plant is abolished by AtVDAC2 expression. PMID- 22301964 TI - Visualization of plastid movement in the pollen tube of Arabidopsis thaliana. AB - Organelle dynamics in the plant male gametophyte has received attention for its importance in pollen tube growth and cytoplasmic inheritance. We recently revealed the dynamic behaviors of plastids in living Arabidopsis pollen grains and tubes, using an inherent promoter-driven FtsZ1-green fluorescent protein (GFP) fusion. Here, we further monitored the movement of pollen tube plastids with an actin1 promoter-driven, stroma-targeted yellow fluorescent protein (YFP). In elongating pollen tubes, most plastids localized to the tube shank, where they displayed either retarded and unsteady motion, or fast, directional, and long distance movement along the tube polarity. Efficient plastid tracking further revealed a population of tip-forwarding plastids that undergo a fluctuating motion(s) before traveling backwards. The behavior of YFP-labeled plastids in pollen basically resembled that of FtsZ1-GFP-labeled plastids, thus validating the use of FtsZ1-GFP for simultaneous visualization of the stroma and the plastid dividing FtsZ ring. PMID- 22301965 TI - Regulation of pyrophosphate levels by H+-PPase is central for proper resumption of early plant development. AB - The synthesis of DNA, RNA, and de novo proteins is fundamental for early development of the seedling after germination, but such processes release pyrophosphate (PPi) as a byproduct of ATP hydrolysis. The over-accumulation of the inhibitory metabolite PPi in the cytosol hinders these biosynthetic reactions. All living organisms possess ubiquitous enzymes collectively called inorganic pyrophosphatases (PPases), which catalyze the hydrolysis of PPi into two orthophosphate (Pi) molecules. Defects in PPase activity cause severe developmental defects and/or growth arrest in several organisms. In higher plants, a proton-translocating vacuolar PPase (H+-PPase) uses the energy of PPi hydrolysis to acidify the vacuole. However, the biological implications of PPi hydrolysis are vague due to the widespread belief that the major role of H+-PPase in plants is vacuolar acidification. We have shown that the Arabidopsis fugu5 mutant phenotype, caused by a defect in H+-PPase activity, is rescued by complementation with the yeast cytosolic PPase IPP1. In addition, our analyses have revealed that increased cytosolic PPi levels impair postgerminative development in fugu5 by inhibiting gluconeogenesis. This led us to the conclusion that the role of H+-PPase as a proton-pump is negligible. Here, we present further evidence of the growth-boosting effects of removing PPi in later stages of plant vegetative development, and briefly discuss the biological role of PPases and their potential applications in different disciplines and in various organisms. PMID- 22301966 TI - The 2b proteins of Cucumber mosaic virus generally have the potential to differentially induce necrosis on Arabidopsis. AB - Plant viral symptoms are rarely explained by direct molecular interaction between a viral protein and a host factor, but rather understood as a consequence of arms race between host RNA silencing and viral silencing suppressors. However, we have recently demonstrated that the 2b protein (2b) of Cucumber mosaic virus (CMV) HL strain could bind to Arabidopsis catalase that is important in scavenging cellular hydrogen peroxide, leading to the induction of distinct necrosis on Arabidopsis. Because we previously used virulent strains of subgroup I CMV in the study, we here further analyzed mild strains of subgroup II CMV, which share 70 to 80% sequence homology with subgroup I, to understand whether the necrosis induction is a general phenomenon to compromise host defense system mediated by catalase in the pathosystem of any CMV strains and Arabidopsis. Based on the results, we concluded that 2bs of subgroup II could also bind to catalase, resulting in decrease in catalase activity and weak necrosis on Arabidopsis. Because the 2b-catalase interaction did not prevent CMVs from spreading, it may eventually operate in favor of CMV. PMID- 22301967 TI - Polar localization and endocytic degradation of a boron transporter, BOR1, is dependent on specific tyrosine residues. AB - Boron (B) is essential for plants, but is toxic in excess. Plants have to strictly regulate the uptake and translocation of B. In Arabidopsis thaliana root cells, a boric acid channel, NIP5;1, and a boric acid/borate exporter, BOR1, localize to the outer (facing soil) and inner plasma membrane domains, respectively, under B limitation. The opposite polar localizations of the importer and exporter would enable plant roots to transport B efficiently towards the xylem. In addition, accumulation of the B transporters is controlled by B conditions. When plants are shifted from low to high B conditions, NIP5;1 transcript accumulation is down-regulated through mRNA degradation. The BOR1 protein is transported to the trans-Golgi network/early endosome and multivesicular body and finally degraded in the vacuole. We have recently shown that both the polar localization and the endocytic degradation of BOR1 are controlled by at least two tyrosine residues in a large loop located in the cytosol. We also showed that ubiquitination is required for the endocytic degradation of BOR1. Here, we analyzed possible involvement of an additional tyrosine residue (Y414) in the loop region and discuss the pathway of the BOR1 trafficking for polar localization and endocytic degradation of BOR1. PMID- 22301968 TI - Role of rice PPS in late vegetative and reproductive growth. AB - The rice peter pan syndrome-1 (pps-1) mutant shows a prolonged juvenile phase and early flowering. Although the early vegetative phase and flowering time of pps-1 have been closely examined, the phenotypes in the late vegetative and reproductive phases are not yet well understood. In the ninth leaf blade of pps 1, the relative length of the midrib was comparable to the sixth leaf blade of wild-type. Moreover, pps-1 had a small inflorescence meristem and small panicles. These phenotypes indicate that in pps-1 the juvenile phase coexists with the late vegetative phase, resulting in small panicles. Gibberellin is known to promote the juvenile-adult phase transition. d18-k is dwarf and has a prolonged juvenile phase. Double mutant (d18-k pps-1) showed the same phenotype as the pps-1, indicating that PPS is upstream of GA biosynthetic genes. PMID- 22301969 TI - SCI1, the first member of the tissue-specific inhibitors of CDK (TIC) class, is probably connected to the auxin signaling pathway. AB - The recent finding of a tissue-specific cell cycle regulator (SCI1) that inhibits cell proliferation/differentiation in the upper pistil points to an unanticipated way of controlling plant morphogenesis. The similarity between the SCI1 RNAi silenced plants and some auxin-related phenotypes suggested that SCI1 could be involved in the auxin signaling pathway. To address this hypothesis, we analyzed the expression of three auxin-related genes in transgenic plants in which SCI1 was silenced and overexpressed. The results showed that the expression levels of the auxin-related genes largely correlated with the SCI1 expression level. Additionally, we analyzed the Arabidopsis SCI1 upstream regulatory region and found putative cis-acting elements also present in the AtCYCB1;1 AtYUC1, AtYUC2 and AtYUC4 URRs, suggesting a cell cycle- and auxin-related transcriptional regulation. Based on our previous and the current studies, we propose SCI1 as a signal transducer engaging auxin signaling and cell division/differentiation. PMID- 22301970 TI - Analysis of LuPME3, a pectin methylesterase from Linum usitatissimum, revealed a variability in PME proteolytic maturation. AB - Pectin methylesterase (PME) catalyses the de-methylesterification of pectin in plant cell walls during cell elongation. (1) Pectins are mainly composed of alpha(1, 4)-D-galacturonosyl acid units that are synthesised in a methylesterified form in the Golgi apparatus to prevent any interaction with Ca2+ ions during their intracellular transport. (2) The highly methylesterified pectins are then secreted into the apoplasm (3) and subsequently de methylesterified in muro by PMEs. This can either induce the formation of pectin gels through the Ca2+ crosslinking of neighbouring non-methylesterified chains or create substrates for pectin-degrading enzymes such as polygalacturonases and pectate lyases for the initiation of cell wall loosening. (4) PMEs belong to a large multigene family. Sixty-six PME-related genes are predicted in the Arabidopsis genome. (1) Among them, we have recently shown that AtPME3 (At3g14310), a major basic PME isoform in A. thaliana, is ubiquitously expressed in vascular tissues and play a role in adventitious rooting. (5) In flax (Linum usitatissimum), three genes encoding PMEs have been sequenced so far, including LuPME3, the orthologue of AtPME3. Analysis of the LuPME3 isoform brings new insights into the processing of these proteins. PMID- 22301971 TI - The role of TaCHP in salt stress responsive pathways. AB - In our previous study, we found wheat TaCHP confers salt tolerance through regulating salt responsive signaling pathways. TaCHP possesses three divergent C1 domains that can specifically bind to phospholipid signaling molecule diacylglycerol (DAG) in animal cells, and most of proteins with this domain have kinase activity. Here, we found that TaCHP localizes both at cytoplasmatic membrane and in nuclei; it has no kinase activity but transcriptional activation activity, and the latter owes to C-terminal two C1 domains. TaCHP transcription was reduced by H2O2 application, but its ectopic expression in Arabidopsis improved both ROS production and scavenging capacity, and enhanced tolerance to H2O2 application. We suggest that TaCHP serve as both a transcription factor and a putative DAG binding protein to confer salt tolerance in part through improving ROS scavenging capacity; which is a component of the cross-talk machinery in the phospholipids-ROS-salt responsive signaling pathways. PMID- 22301972 TI - Green light signaling and adaptive response. AB - To a plant, the sun's light is not exclusively energy for photosynthesis, it also provides information about time and prevailing conditions. The plant's surroundings may dampen or filter solar energies, presenting plants with different spectral profiles of their light environment. Plants use this information to adjust form and physiology, tailoring gene expression to best match ambient conditions. Extensive literature exists on how blue, red and far red light contribute to plant adaptive responses. A growing body of work identifies effects of green light (500-565 nm) that also shape plant biology. Green light responses are known to be either mediated through, or independent of, the cryptochrome blue light receptors. Responses to green light share a general tendency to oppose blue- or red-light-induced responses, including stem growth rate inhibition, anthocyanin accumulation and chloroplast gene expression. Recent evidence demonstrates a role for green light in sensing a shaded environment, independent from far-red shade responses. PMID- 22301973 TI - The modulating effect of bacterial volatiles on plant growth: current knowledge and future challenges. AB - Bacteria interact with plants in many different ways. In recent years, bacterial production of volatiles has emerged as a novel process by which bacteria modulate plant growth. Exposure to the volatiles produced by certain bacterial strains has been shown to lead to up to 5-fold increased plant biomass or to plant death. Despite these drastic growth alterations, the elucidation of the molecules responsible, of the mechanism of perception by the plant and of the specific metabolic changes induced in planta is still in its infancy. This review summarizes the current knowledge and highlights future lines of research that should increase our knowledge of the volatile-mediated dialogue between bacteria and plants. PMID- 22301974 TI - Diverse roles of Groucho/Tup1 co-repressors in plant growth and development. AB - Transcriptional regulation involves coordinated and often complex interactions between activators and repressors that together dictate the temporal and spatial activity of target genes. While the study of developmental regulation has often focused on positively acting transcription factors, it is becoming increasingly clear that transcriptional repression is a key regulatory mechanism underpinning many developmental processes in both plants and animals. In this review, we focus on the plant Groucho (Gro)/Tup1-like co-repressors and discuss their roles in establishing the apical-basal axis of the developing embryo, maintaining the stem cell population in the shoot apex and determining floral organ identity. As well as being developmental regulators, recent studies have shown that these co repressors play a central role in regulating auxin and jasmonate signalling pathways and are also linked to the regulation of pectin structure in the seed coat. These latest findings point to the Gro/Tup1-like co-repressors playing a much broad role in plant growth and development than previously thought; an observation that underlines the central importance of transcriptional repression in plant gene regulation. PMID- 22301975 TI - Salicylic acids: local, systemic or inter-systemic regulators? AB - Salicylic acid is well known phytohormone, emerging recently as a new paradigm of an array of manifestations of growth regulators. The area unleashed yet encompassed the applied agriculture sector to find the roles to strengthen the crops against plethora of abiotic and biotic stresses. The skipped part of integrated picture, however, was the evolutionary insight of salicylic acid to either allow or discard the microbial invasion depending upon various internal factors of two interactants under the prevailing external conditions. The metabolic status that allows the host invasion either as pathogenesis or symbiosis with possible intermediary stages in close systems has been tried to underpin here. PMID- 22301976 TI - The root endophyte fungus Piriformospora indica leads to early flowering, higher biomass and altered secondary metabolites of the medicinal plant, Coleus forskohlii. AB - This study was undertaken to investigate the influence of plant probiotic fungus Piriformospora indica on the medicinal plant C. forskohlii. Interaction of the C. forskohlii with the root endophyte P. indica under field conditions, results in an overall increase in aerial biomass, chlorophyll contents and phosphorus acquisition. The fungus also promoted inflorescence development, consequently the amount of p-cymene in the inflorescence increased. Growth of the root thickness was reduced in P. indica treated plants as they became fibrous, but developed more lateral roots. Because of the smaller root biomass, the content of forskolin was decreased. The symbiotic interaction of C. forskohlii with P. indica under field conditions promoted biomass production of the aerial parts of the plant including flower development. The plant aerial parts are important source of metabolites for medicinal application. Therefore we suggest that the use of the root endophyte fungus P. indica in sustainable agriculture will enhance the medicinally important chemical production. PMID- 22301977 TI - Peroxyacetyl nitrate-induced oxidative and calcium signaling events leading to cell death in ozone-sensitive tobacco cell-line. AB - It has long been concerned that some secondary air pollutants such as smog components, ozone (O3) and peroxyacetyl nitrate (PAN), are highly phytotoxic even at low concentrations. Compared with the biology of O3, we largely lack the information on the toxicity model for PAN at the cellular signaling levels. Here, we studied the cell-damaging impact of PAN using suspension culture of smog sensitive tobacco variety (Bel-W3). The cells were exposed to freshly synthesized PAN and the induced cell death was assessed under microscope after staining with Evans blue. Involvement of reactive oxygen species (ROS) in PAN toxicity was suggested by PAN-dependently increased intracellular H2O2 and also by the cell protective effects of ROS scavengers and related inhibitors. Calcium chelator also lowered the level of PAN-induced cell death, indicating that Ca2+ is also involved. Using a transgenic cell line expressing aequorin, an increase in cytosolic Ca2+ concentration responsive to the pulse of PAN, but sensitive to Ca2+ channel blockers, was recorded, indicating that Ca2+ channels are activated by PAN or PAN-derived signals. Above data show some similarity between the signaling mechanisms responsive to O3 and PAN. PMID- 22301978 TI - Pretreatments, conditioned medium and co-culture increase the incidence of somatic embryogenesis of different Cichorium species. AB - Somatic embryogenesis (SE) in Cichorium involves dedifferentiation and redifferentiation of single cells and can be induced by specific in vitro culture conditions. We have tested the effect of various treatments on the incidence of SE (ISE) of an interspecific embryogenic hybrid (C. endivia x C. intybus) and of different commercial chicories (C. endivia and C. intybus) that are typically recalcitrant to SE in standard culture conditions. We found that the ISE of the hybrid is significantly increased by pretreatment of tissues by submersion in solutions of glycerol, abscisic acid, spermine, putrescine or of combinations of these compounds. Interestingly, the most efficient of these pretreatments also had an unexpectedly high effect on the ISE of the C. intybus cultivars. The ISE of the hybrid and of the commercial chicories were increased when explants were co-cultured with highly embryogenic chicory explants or when they were cultured in conditioned medium. These observations established that unidentified SE promoting factors are released in the culture medium. HPLC analyses of secreted Arabino-Galactan Proteins (AGPs), which are known to stimulate SE, did not allow identifying a fraction containing differentially abundant AGP candidates. However, pointing to their role in promoting SE, we found that the hybrid had a drastically higher ISE when amino sugars and L-Proline, the putative precursors of secreted AGPs, were both added to the medium. PMID- 22301979 TI - Changes in RACK1 expression induce defects in nodulation and development in Phaseolus vulgaris. AB - RACK1 is a scaffold protein with the ability to interact in a regulated manner with a diverse number of ligands from distinct signal-transduction pathways. This assessment allowed us to infer that it may be involved in different processes such as nodulation. In a recent study we showed by silencing, that PvRACK1 has a pivotal role in cell expansion and in symbiosome and bacteroid integrity during nodule development in Phaseolus vulgaris. On the other hand, we have also observed that its over-expression provokes a dramatic phenotype in: (a) seedlings that have been exposed to heat, in which systemic necrosis is induced; and (b) in Agrobacterium rhizogenes-transformed roots, where nodulation is strongly inhibited and nodules show early senescent symptoms. These findings indicate that PvRACK1 may be an integrator of diverse signal-transduction pathways in processes as varied as nodulation, cell expansion, heat stress responses, and systemic activation of necrosis. PMID- 22301980 TI - KNAT1, KNAT2 and KNAT6 act downstream in the IDA-HAE/HSL2 signaling pathway to regulate floral organ abscission. AB - Cell separation processes, such as abscission, are critical for plant development and play key roles from sculpting the form of the plant to scattering seeds. It is however essential that such processes are under tight temporal and spatial regulation. Floral organ abscission in Arabidopsis thaliana is regulated by a ligand-receptor module consisting of the signaling peptide INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) and the two receptor-like kinases HAESA (HAE) and HAESA-LIKE 2 (HSL2), and it is the restricted expression pattern of IDA that hinders cell separation from occurring in the abscission zones (AZs) of other organs where HAE and HSL2 are present. In the July issue of The Plant Cell we report on the identification of additional components acting downstream in the IDA signaling pathway. Through a screen for mutations that restore floral organ abscission in ida mutants, we identified two new alleles of the KNOTTED-LIKE HOMEOBOX gene BREVIPEDICELLUS (BP)/KNOTTED-LIKE FROM ARABIDOPSIS THALIANA1 (KNAT1) and show that BP/KNAT1 is important in regulating the timing of floral abscission by controlling AZ cell size and by regulating KNAT2 and KNAT6. PMID- 22301981 TI - Stabilization of thylakoid membranes in isoprene-emitting plants reduces formation of reactive oxygen species. AB - Isoprene is emitted by a significant fraction of the world's vegetation. Isoprene makes leaves more thermotolerant, yet we do not fully understand how. We have recently shown that isoprene stabilizes thylakoid membranes under heat stress. Here we show that heat-stressed, isoprene-emitting transgenic Arabidopsis plants also produce a lower pool of reactive oxygen and reactive nitrogen species, and that this was especially due to a lower accumulation of H2O2 in isoprene emitting plants. It remains difficult to disentangle whether in heat stressed plants isoprene also directly reacts with and quenches reactive oxygen species (ROS), or reduces ROS formation by stabilizing thylakoids. We present considerations that make the latter a more likely mechanism, under our experimental circumstances. PMID- 22301982 TI - Retrograde signals arise from reciprocal crosstalk within plastids. AB - In addition to the cell nucleus, plant cells also possess genomic DNA and gene expression machineries within mitochondria and plastids. In higher plants, retrograde transcriptional regulation of several nuclear genes encoding plastid located proteins has been observed in response to changes in a wide variety of physiological properties in plastids, including organelle gene expression (OGE) and tetrapyrrole metabolism. This regulation is postulated to be accomplished by plastid-to-nucleus signaling, (1,2) although the overall signal transduction pathway(s) are not well characterized. By applying a specific differentiation system in tobacco Bright Yellow-2 (BY-2) cultured cells, (3,4) we recently reported that the regulatory system of nuclear gene expressions modulated by a plastid signal was also observed during differentiation of plastids into amyloplasts. (5) While retrograde signaling from plastids was previously speculated to consist of several independent pathways, we found inhibition of OGE and perturbation in the cellular content of one tetrapyrrole intermediate, heme, seemed to interact to regulate amyloplast differentiation. Our results thus highlight the possibility that several sources of retrograde signaling in plastids could be integrated in an intraorganellar manner. PMID- 22301983 TI - Characterization of the membrane-associated HaRxL17 Hpa effector candidate. AB - We examined changes to subcellular architecture during the compatible interaction between the biotroph pathogen Hyaloperonospora arabidopsidis (Hpa) and its host Arabidopsis. Live-cell imaging highlighted rearrangements in plant cell membranes upon infection. In particular, the tonoplast appeared close to the extrahaustorial membrane surrounding the haustorium. We investigated the subcellular localization patterns of Hpa RxLR effector candidates (HaRxLs) in planta. This subcellular localization screening led to the identification of an extrahaustorial membrane-localized effector, HaRxL17 that when stably expressed in Arabidopsis increased plant susceptibility to Hpa during compatible and incompatible interactions. Here, we report that the N-terminal part of HaRxL17 is sufficient to target the plant cell membranes. We showed that both C- or N terminal fluorescent-tagged HaRxL17 localizes around Hpa haustoria, in early and in late stages of infection. As with Hpa infection, GFP-HaRxL17 also localizes around haustoria during infection with Albugo laibachii. Thus, HaRxL17 that increases plant susceptibility to Hpa during both compatible and incompatible interactions, localizes around oomycete haustoria when stably expressed in Arabidopsis. PMID- 22301984 TI - Is minimally invasive retroperitoneal pancreatic necrosectomy too aggressive in treating infected pancreatic necrosis. PMID- 22301985 TI - Left superior vena cava: revisited. AB - The persistence of a left-sided superior vena cava is the most common variant of systemic venous drainage. Increased utility of cardiac imaging, in particular cross-sectional techniques such as computed tomography and magnetic resonance (MR), will result in increased detection of the anomaly and its variants. Whilst in the typical form it is often haemodynamically insignificant, its discovery may have clinical significance nonetheless, and its mimics require exclusion. During cardiac development the anomaly results from a failure of the left anterior cardinal vein to obliterate. Recognized anatomical variants include the absence of the right superior vena cava and of an innominate bridging vein. Typical drainage is to the coronary sinus, dilatation of which may be the first hint to the anomaly. Clinical implications with respect to vascular access and arrhythmia are well described. A significant minority drain into the left atrium, potentially creating a haemodynamically significant lesion. Additionally, differentiation from anomalous left upper pulmonary venous drainage via a vertical vein is mandatory. A newly discovered variant runs an intra-atrial course with subsequent typical drainage, and if not recognized as such, may be confused with a left atrial mass. The use of 3D contrast-enhanced MR venography has proven extremely helpful in characterizing anomalous vasculature, and we demonstrate how such techniques can help delineate the anomaly and differentiate from its mimics. PMID- 22301987 TI - The 60-film set with 8-index for examining physicians' proficiency in reading pneumoconiosis chest X-rays. AB - The 60-film set was developed by experts (Expert Group) for examining 8 indices: sensitivity (X(1)) and specificity (X(2)) for pneumoconiosis, sensitivity(X(3)) and specificity for (X(4)) large opacities, sensitivity (X(5)) and specificity (X(6)) for pleural plaque, profusion increment consistency for small opacities (X(7)), and shape differentiation for small opacities (X(8)) of physicians' reading skills on pneumoconiosis X-ray according to ILO 2000 Classification. The aim of this study was to assess the appropriateness of the exam film set for evaluating physicians' reading skills. 29 physicians (A1-Group) and 24 physicians (A2-Group) attended the 1st and 2nd "Asian Intensive Reader of Pneumoconioses" (AIR Pneumo) training course, respectively, and 22 physicians (B-Group) attended Brazilian training course. After training, they took examination of reading 60 film exam set. The examinees' reading results in terms of 8 indices were compared between the examinee groups and the Expert Group by parametric unpaired t-test. The Examinee Group consisting of A1-Group, A2-Group and B-Group was inferior to the Expert Group in all indices. There was no significant difference for X(7) of A1-Group, X(7) and X(8) of A2-Group (p>0.05) compared with the Expert Group. There was a significant difference in X(8) at p<0.05 between A1-Group and A2 Group, in X(3) at p<0.05 between A1-Group and B-Group, in both X(1) and in X(3) at p<0.05 between A2-Group and B-Group. Accordingly, the 60-film set providing 8 indices designed might be a good method for evaluation of the physicians' reading proficiency at different training settings. PMID- 22301988 TI - Influence of the municipal merger on local government employees' stress response in Japan. AB - In Japan, mergers of cities, towns, and villages have occurred rapidly as a result of the Special Law on the Merger of Municipalities, enacted in 2005. These mergers may impact civil servants' psychological adjustment. We developed the Municipal Merger Stress Questionnaire (MMSQ) to measure the impact of the municipal mergers and collected responses from 570 employees who had experienced a municipal merger (Study 1). We examined the relationships among the impact of municipal merger, Stress Responses, Self-concept (self-esteem and interpersonal dependency), and Social Support (Study 2). Two factors (Increased Workload and Worthlessness) were derived from the MMSQ in Study 1. Additionally, a structural equation model showed that the impact of the loss of value of their job (Worthlessness) related to the psychological stress responses, while job discretion did not differentiate an entire stress situation in Study 2. The result implies that psychological aspects of interventions focused on worthlessness are required to maintain good mental health of public servants at workplaces. PMID- 22301990 TI - Autophagy defects in Lafora disease: cause or consequence? AB - Lafora disease (LD) is an inherited and fatal form of neurodegenerative disorder characterized by the presence of an abnormal form of glycogen inclusions, called Lafora bodies, in neurons and other tissues. While Lafora bodies have been thought to underlie the neuropathology in LD, the specific process by which these inclusions might affect the neuronal functions was not very well understood. Here we review one of our recent studies on the LD animal model, wherein we have shown that the Lafora bodies might contribute to the impairment in the endosomal lysosomal and autophagy pathways. PMID- 22301991 TI - Axonal damage, autophagy and neuronal survival. AB - In recent years autophagy modulation has been shown to reduce or increase neuronal cell death in several models of neurodegeneration. How autophagy exerts these dual effects is currently unknown. Here we review recent evidence from our laboratory demonstrating that autophagy can protect the cell soma after axonal traumatic injury. Damage in the optic nerve induces retinal ganglion cell (RGC) death in glaucoma and other retinal diseases and is often modeled by axotomy of the optic nerve in laboratory animals. Using this well-known model of RGC degeneration we show that autophagy is strongly upregulated following the insult and before cell death. Enhancement of autophagy by pharmacological treatment with rapamycin decreases the number of degenerating neurons. Conversely, axotomy in Atg4B (-/-) mice increases the number of dying cells in the retinal ganglion cell layer. Similar findings were observed in Atg5 (flox/flox) mice following specific downregulation of the autophagy regulator ATG5 in RGCs, by intravitreal injection of a cre-expressing vector. Taken together, these findings point to a cytoprotective role of autophagy following axonal damage in vivo. PMID- 22301992 TI - The amplified cancer gene LAPTM4B promotes tumor growth and tolerance to stress through the induction of autophagy. AB - Autophagy is a fundamental salvage pathway that encapsulates damaged cellular components and delivers them to the lysosome for degradation and recycling. This pathway usually conducts a protective cellular response to nutrient deprivation and various stresses. Tumor cells live with metabolic stress and use autophagy for their survival during tumor progression and metastasis. Genomic instability in tumor cells may result in amplification of crucial gene(s) for autophagy and upregulate the autophagic pathway. We demonstrate that a cancer-associated gene, LAPTM4B, plays an important role in lysosomal functions and is critical for autophagic maturation. Its amplification and overexpression promote autophagy, which renders tumor cells resistant to metabolic and genotoxic stress and results in more rapid tumor growth. PMID- 22301993 TI - Targeting HMGB1-mediated autophagy as a novel therapeutic strategy for osteosarcoma. AB - Autophagy is a catabolic process critical to maintaining cellular homeostasis and responding to cytotoxic insult. Autophagy is recognized as "programmed cell survival" in contrast to apoptosis or programmed cell death. Upregulation of autophagy has been observed in many types of cancers and has been demonstrated to both promote and inhibit antitumor drug resistance depending to a large extent on the nature and duration of the treatment-induced metabolic stress as well as the tumor type. Cisplatin, doxorubicin and methotrexate are commonly used anticancer drugs in osteosarcoma, the most common form of childhood and adolescent cancer. Our recent study demonstrated that high mobility group box 1 protein (HMGB1) mediated autophagy is a significant contributor to drug resistance in osteosarcoma cells. Inhibition of both HMGB1 and autophagy increase the drug sensitivity of osteosarcoma cells in vivo and in vitro. Furthermore, we demonstrated that the ULK1-FIP200 complex is required for the interaction between HMGB1 and BECN1, which then promotes BECN1-PtdIns3KC3 complex formation during autophagy. Thus, these findings provide a novel mechanism of osteosarcoma resistance to therapy facilitated by HMGB1-mediated autophagy and provide a new target for the control of drug-resistant osteosarcoma patients. PMID- 22301994 TI - MAP1S enhances autophagy to suppress tumorigenesis. AB - Microtubule-associated protein 1 small form (MAP1S; originally named C19ORF5) was identified as serving as linkers to connect mitochondria with microtubules for trafficking, and to bridge the autophagy machinery with microtubules and mitochondria to affect autophagosomal biogenesis and degradation. We found that MAP1S levels become elevated immediately in response to diethylnitrosamine induced or genome instability-driven metabolic stress in a murine model of hepatocarcinoma. Elevation of MAP1S enhances autophagy to remove p62-associated aggresomes and dysfunctional organelles that trigger DNA double-strand (DSB) breaks and genome instability. The early accumulation of an unstable genome prior to signs of tumorigenesis suggested that genome instability causes tumorigenesis. After tumorigenesis, tumor development then triggers the activation of autophagy to reduce genome instability in tumor foci. We concluded that an increase in MAP1S levels triggers autophagy in order to suppress genome instability so that both the incidence of diethylnitrosamine-induced hepatocarcinogenesis and malignant progression are suppressed. Thus, a link between MAP1S-enhanced autophagy and suppression of genomic instability and tumorigenesis has been established. PMID- 22301995 TI - Alpha-synuclein's degradation in vivo: opening a new (cranial) window on the roles of degradation pathways in Parkinson disease. AB - Progressive accumulation of alpha-synuclein is key to the pathology of many neurodegenerative diseases, including Parkinson disease and dementia with Lewy bodies. Increased intracellular levels of alpha-synuclein may be caused by enhanced expression or alterations in protein degradation pathways. Here we review our recent study showing that the ubiquitin-proteasome system and the autophagy-lysosomal pathway are differentially involved in alpha-synuclein's degradation in vivo. We discuss the key findings obtained with our novel in vivo approach and also present a model for the progression of protein aggregation and dysfunctional degradation in Parkinson disease. PMID- 22301996 TI - (Pro)renin receptor and autophagy in podocytes. AB - Within the kidneys, podocytes are highly specialized postmitotic cells. Podocytes, together with endothelial cells and the glomerular basement membrane (GBM), maintain the filtration barrier and the normal structure of the glomerular capillary, are involved in the remodeling of the GBM and the endocytosis of filtered proteins, and counteract intracapillary hydrostatic pressure. The (pro)renin receptor [(P)RR], as ATP6AP2, is an accessory subunit of the vacuolar H (+) -ATPase, implying more fundamental developmental functions for the (pro)renin receptor in addition to its role in activating the local renin angiotensin system, and is also expressed in podocytes, where it is involved in both tissue angiotensin II production and (P)RR-mediated intracellular signaling. Overexpression of human (P)RR in rats caused slowly progressive proteinuria and glomerular sclerosis, which suggests that (P)RR-mediated signaling is involved in the development of glomerular diseases. However, the physiological role of the (P)RR in podocytes has not yet been fully understood. PMID- 22301997 TI - Direct molecular interactions between Beclin 1 and the canonical NFkappaB activation pathway. AB - General (macro)autophagy and the activation of NFkappaB constitute prominent responses to a large array of intracellular and extracellular stress conditions. The depletion of any of the three subunits of the inhibitor of NFkappaB (IkappaB) kinase (IKKalpha, IKKbeta, IKKgamma/NEMO), each of which is essential for the canonical NFkappaB activation pathway, limits autophagy induction by physiological or pharmacological triggers, while constitutive active IKK subunits suffice to stimulate autophagy. The activation of IKK usually relies on TGFbeta activated kinase 1 (TAK1), which is also necessary for the optimal induction of autophagy in multiple settings. TAK1 interacts with two structurally similar co activators, TAK1-binding proteins 2 and 3 (TAB2 and TAB3). Importantly, in resting conditions both TAB2 and TAB3 bind the essential autophagic factor Beclin 1, but not TAK1. In response to pro-autophagic stimuli, TAB2 and TAB3 dissociate from Beclin 1 and engage in stimulatory interactions with TAK1. The inhibitory interaction between TABs and Beclin 1 is mediated by their coiled-coil domains (CCDs). Accordingly, the overexpression of either TAB2 or TAB3 CCD stimulates Beclin 1- and TAK1-dependent autophagy. These results point to the existence of a direct molecular crosstalk between the canonical NFkappaB activation pathway and the autophagic core machinery that guarantees the coordinated induction of these processes in response to stress. PMID- 22301998 TI - Distribution of total mercury in surface sediments of the western Jade Bay, Lower Saxonian Wadden Sea, southern North Sea. AB - A total of 114 surface sediment samples was equidistantly collected in the western part of the Jade Bay, southern North Sea, to analyse total mercury contents as well as grain size distribution and total organic carbon (TOC) contents. Total mercury was determined by oxygen combustion-gold amalgamation. Validation, precision and accuracy of the method were evaluated and controlled with two certified reference materials (HISS-1 and MESS-3). Total mercury contents varied between 8 and 243 ng/g dry sediment with a mean value of 103 ng/g dw. The mercury levels in surface sediments showed an inhomogeneous spatial distribution with higher contents in near-dike areas. The values are mostly in the range of natural background values (50-100 ng/g dw) and positively related to TOC and clay/silt contents (<63 MUm). The present total mercury contents are compared to those of previous studies, in order to estimate possible temporal trends of mercury contents in the study area over the last decades. Moreover, the comparison to sediment quality guidelines indicated that the surface sediments of the Jade Bay are not mercury contaminated. These results also suggested that the current mercury contents of Jade Bay surficial sediments are mostly affected by atmospheric deposition and re-emission. PMID- 22301999 TI - Protocols, toolboxes and resource papers. AB - In the August 2009 issue of Autophagy, I indicated that we were launching a new category of article, Protocols. At that time, I noted that we would ultimately be placing these articles on a new site online. Well, that time has finally arrived (see www.landesbioscience.com/journals/autophagy/protocols/ for links to these papers). Therefore, it seems appropriate for me to briefly distinguish among three types of community-oriented papers, Protocol, Toolbox and Resource. PMID- 22302000 TI - PKD at the crossroads of necrosis and autophagy. AB - Reactive oxygen species (ROS) that accumulate under oxidative pressure cause severe damage to cellular components, and induce various cellular responses, including apoptosis, programmed necrosis and autophagy, depending on the cellular setting. Various studies have described ROS-induced autophagy, but only a few direct factors that regulate autophagy under oxidative stress are known to date. We have identified DAPK and PKD as such regulators by demonstrating their role in the process of autophagy in general, and specifically during oxidative stress. PKD acts as a downstream effector of DAPk in the regulation of autophagy. Furthermore, PKD functions within the autophagic network as an activator of VPS34, by associating with and phosphorylating VPS34, leading to its activation. Significantly, PKD is recruited to the autophagosomal membranes, placing it within proximity of its autophagic target. PMID- 22302001 TI - Autophagic proteins: new facets of the oxygen paradox. AB - Oxygen (O 2), while essential for aerobic life, can also cause metabolic toxicity through the excess generation of reactive oxygen species (ROS). Pathological changes in ROS production can originate through the partial reduction of O 2 during mitochondrial electron transport, as well as from enzymatic sources. This phenomenon, termed the oxygen paradox, has been implicated in aging and disease, and is especially evident in critical care medicine. Whereas high O 2 concentrations are utilized as a life-sustaining therapeutic for respiratory insufficiency, they in turn can cause acute lung injury. Alveolar epithelial cells represent a primary target of hyperoxia-induced lung injury. Recent studies have indicated that epithelial cells exposed to high O 2 concentrations die by apoptosis, or necrosis, and can also exhibit mixed-phenotypes of cell death (aponecrosis). Autophagy, a cellular homeostatic process responsible for the lysosomal turnover of organelles and proteins, has been implicated as a general response to oxidative stress in cells and tissues. This evolutionarily conserved process is finely regulated by a complex interplay of protein factors. During autophagy, senescent organelles and cellular proteins are sequestered in autophagic vacuoles (autophagosomes) and subsequently targeted to the lysosome, where they are degraded by lysosomal hydrolases, and the breakdown products released for reutilization in anabolic pathways. Autophagy has been implicated as a cell survival mechanism during nutrient-deficiency states, and more generally, as a determinant of cell fate. However, the mechanisms by which autophagy and/or autophagic proteins potentially interact with and/or regulate cell death pathways during high oxygen stress, remain only partially understood. PMID- 22302002 TI - Maternal inheritance of mitochondrial DNA: degradation of paternal mitochondria by allogeneic organelle autophagy, allophagy. AB - Maternal inheritance of mitochondrial DNA (mtDNA) is generally observed in many eukaryotes. Sperm-derived paternal mitochondria and their mtDNA enter the oocyte cytoplasm upon fertilization and then normally disappear during early embryogenesis. However, the mechanism underlying this clearance of paternal mitochondria has remained largely unknown. Recently, we showed that autophagy is required for the elimination of paternal mitochondria in Caenorhabditis elegans embryos. Shortly after fertilization, autophagosomes are induced locally around the penetrated sperm components. These autophagosomes engulf paternal mitochondria, resulting in their lysosomal degradation during early embryogenesis. In autophagy-defective zygotes, paternal mitochondria and their genomes remain even in the larval stage. Therefore, maternal inheritance of mtDNA is accomplished by autophagic degradation of paternal mitochondria. We also found that another kind of sperm-derived structure, called the membranous organelle, is degraded by zygotic autophagy as well. We thus propose to term this allogeneic (nonself) organelle autophagy as allophagy. PMID- 22302003 TI - Carotenoid deficiency triggers autophagy in the model green alga Chlamydomonas reinhardtii. AB - All aerobic organisms have developed sophisticated mechanisms to prevent, detect and respond to cell damage caused by the unavoidable production of reactive oxygen species (ROS). Plants and algae are able to synthesize specific pigments in the chloroplast called carotenoids to prevent photo-oxidative damage caused by highly reactive by-products of photosynthesis. In this study we used the unicellular green alga Chlamydomonas reinhardtii to demonstrate that defects in carotenoid biosynthesis lead to the activation of autophagy, a membrane trafficking process that participates in the recycling and degradation of damaged or toxic cellular components. Carotenoid depletion caused by either the mutation of phytoene synthase or the inhibition of phytoene desaturase by the herbicide norflurazon, resulted in a strong induction of autophagy. We found that high light transiently activates autophagy in wild-type Chlamydomonas cells as part of an adaptation response to this stress. Our results showed that a Chlamydomonas mutant defective in the synthesis of specific carotenoids that accumulate during high light stress exhibits constitutive autophagy. Moreover, inhibition of the ROS-generating NADPH oxidase partially reduced the autophagy induction associated to carotenoid deficiency, which revealed a link between photo-oxidative damage, ROS accumulation and autophagy activation in Chlamydomonas cells with a reduced carotenoid content. PMID- 22302004 TI - A high-throughput FRET-based assay for determination of Atg4 activity. AB - Atg4 is required for cleaving Atg8, allowing it to be conjugated to phosphatidylethanolamine on phagophore membranes, a key step in autophagosome biogenesis. Deconjugation of Atg8 from autophagosomal membranes could be also a regulatory step in controlling autophagy. Therefore, the activity of Atg4 is important for autophagy and could be a target for therapeutic intervention. In this study, a sensitive and specific method to measure the activity of two Atg4 homologs in mammalian cells, Atg4A and Atg4B, was developed using a fluorescence resonance energy transfer (FRET)-based approach. Thus LC3B and GATE-16, two substrates that could be differentially cleaved by Atg4A and Atg4B, were fused with CFP and YFP at the N- and C-terminus, respectively, allowing FRET to occur. The FRET signals decreased in proportion to the Atg4-mediated cleavage, which separated the two fluorescent proteins. This method is highly efficient for measuring the enzymatic activity and kinetics of Atg4A and Atg4B under in vitro conditions. Applications of the assay indicated that the activity of Atg4B was dependent on its catalytic cysteine and expression level, but showed little changes under several common autophagy conditions. In addition, the assays displayed excellent performance in high throughput format and are suitable for screening and analysis of potential modulators. In summary, the FRET-based assay is simple and easy to use, is sensitive and specific, and is suitable for both routine measurement of Atg4 activity and high-throughput screening. PMID- 22302005 TI - Andrographolide sensitizes cisplatin-induced apoptosis via suppression of autophagosome-lysosome fusion in human cancer cells. AB - Suppression of autophagy has been increasingly recognized as a novel cancer therapeutic approach. Andrographolide (Andro), a diterpenoid lactone isolated from an herbal plant Andrographis paniculata, is known to possess anti inflammatory and anticancer activity. In this study, we sought to examine the effect of Andro on autophagy, and to evaluate whether such effect is relevant to the sensitization effect of Andro on apoptosis induced by DNA damage agents in cancer cells. First, we found that Andro is able to significantly enhance autophagic markers in various cancer cell lines, including GFP-LC3 puncta and LC3 II level. Interestingly, Andro treatment also led to marked increase of p62 protein level and addition of chloroquine (CQ) failed to further enhance either LC3-II or p62 level, indicating that Andro is likely to suppress autophagic flux at the maturation and degradation stage. Next, we provided evidence that Andro inhibits autophagosome maturation not by affecting the lysosomal function, but by impairing autophagosome-lysosome fusion. Lastly, we demonstrated that treatment with cisplatin, a DNA damage agent, induces autophagy in cancer cells. Importantly, Andro is capable of sensitizing cisplatin-induced cell killing determined with both short-term apoptosis assays and long-term clonogenic test, via suppression of autophagy, a process independent of p53. In summary, these observations collectively suggest that Andro could be a promising anti-cancer agent in combination therapy via its potent inhibitory effect on autophagy by disrupting autophagosome-lysosome fusion. PMID- 22302006 TI - Enhancing lysosome biogenesis attenuates BNIP3-induced cardiomyocyte death. AB - Hypoxia-inducible pro-death protein BNIP3 (BCL-2/adenovirus E1B 19-kDa interacting protein 3), provokes mitochondrial permeabilization causing cardiomyocyte death in ischemia-reperfusion injury. Inhibition of autophagy accelerates BNIP3-induced cell death, by preventing removal of damaged mitochondria. We tested the hypothesis that stimulating autophagy will attenuate BNIP3-induced cardiomyocyte death. Neonatal rat cardiac myocytes (NRCMs) were adenovirally transduced with BNIP3 (or LacZ as control; at multiplicity of infection = 100); and autophagy was stimulated with rapamycin (100 nM). Cell death was assessed at 48 h. BNIP3 expression increased autophagosome abundance 8 fold and caused a 3.6-fold increase in cardiomyocyte death as compared with control. Rapamycin treatment of BNIP3-expressing cells led to further increase in autophagosome number without affecting cell death. BNIP3 expression led to accumulation of autophagosome-bound LC3-II and p62, and an increase in autophagosomes, but not autolysosomes (assessed with dual fluorescent mCherry-GFP LC3 expression). BNIP3, but not the transmembrane deletion variant, interacted with LC3 and colocalized with mitochondria and lysosomes. However, BNIP3 did not target to lysosomes by subcellular fractionation, provoke lysosome permeabilization or alter lysosome pH. Rather, BNIP3-induced autophagy caused a decline in lysosome numbers with decreased expression of the lysosomal protein LAMP-1, indicating lysosome consumption and consequent autophagosome accumulation. Forced expression of transcription factor EB (TFEB) in BNIP3 expressing cells increased lysosome numbers, decreased autophagosomes and increased autolysosomes, prevented p62 accumulation, removed depolarized mitochondria and attenuated BNIP3-induced death. We conclude that BNIP3 expression induced autophagosome accumulation with lysosome consumption in cardiomyocytes. Forced expression of TFEB, a lysosomal biogenesis factor, restored autophagosome processing and attenuated BNIP3-induced cell death. PMID- 22302007 TI - The fibroblast growth factor signaling axis controls cardiac stem cell differentiation through regulating autophagy. AB - The fibroblast growth factor (FGF) signaling axis plays important roles in heart development. Yet, the molecular mechanism by which the FGF regulates cardiogenesis is not fully understood. Using genetically engineered mouse and in vitro cultured embryoid body (EB) models, we demonstrate that FGF signaling suppresses premature differentiation of heart progenitor cells, as well as autophagy in outflow tract (OFT) myocardiac cells. The FGF also promotes mesoderm differentiation in embryonic stem cells (ESCs) but inhibits cardiomyocyte differentiation of the mesoderm cells at later stages. Furthermore, inhibition of FGF signaling increases myocardial differentiation and autophagy in both ex vivo cultured embryos and EBs, whereas activation of autophagy promotes myocardial differentiation. Thus, a link between FGF signals preventing premature differentiation of heart progenitor cells and suppression of autophagy has been established. These findings provide the first evidence that autophagy plays a role in heart progenitor differentiation, and suggest a new venue to regulate stem/progenitor cell differentiation. PMID- 22302008 TI - Autophagy: a cyto-protective mechanism which prevents primary human hepatocyte apoptosis during oxidative stress. AB - The role of autophagy in the response of human hepatocytes to oxidative stress remains unknown. Understanding this process may have important implications for the understanding of basic liver epithelial cell biology and the responses of hepatocytes during liver disease. To address this we isolated primary hepatocytes from human liver tissue and exposed them ex vivo to hypoxia and hypoxia reoxygenation (H-R). We showed that oxidative stress increased hepatocyte autophagy in a reactive oxygen species (ROS) and class III PtdIns3K-dependent manner. Specifically, mitochondrial ROS and NADPH oxidase were found to be key regulators of autophagy. Autophagy involved the upregulation of BECN1, LC3A, Atg7, Atg5 and Atg 12 during hypoxia and H-R. Autophagy was seen to occur within the mitochondria of the hepatocyte and inhibition of autophagy resulted in the lowering a mitochondrial membrane potential and onset of cell death. Autophagic responses were primarily observed in the large peri-venular (PV) hepatocyte subpopulation. Inhibition of autophagy, using 3-methyladenine, increased apoptosis during H-R. Specifically, PV human hepatocytes were more susceptible to apoptosis after inhibition of autophagy. These findings show for the first time that during oxidative stress autophagy serves as a cell survival mechanism for primary human hepatocytes. PMID- 22302009 TI - A novel method for autophagy detection in primary cells: impaired levels of macroautophagy in immunosenescent T cells. AB - Autophagy is a conserved constitutive cellular process, responsible for the degradation of dysfunctional proteins and organelles. Autophagy plays a role in many diseases such as neurodegeneration and cancer; however, to date, conventional autophagy detection techniques are not suitable for clinical samples. We have developed a high throughput, statistically robust technique that quantitates autophagy in primary human leukocytes using the Image stream, an imaging flow cytometer. We validate this method on cell lines and primary cells knocked down for essential autophagy genes. Also, using this method we show that T cells have higher autophagic activity than B cells. Furthermore our results indicate that healthy primary senescent CD8(+) T cells have decreased autophagic levels correlating with increased DNA damage, which may explain features of the senescent immune system and its declining function with age. This technique will allow us, for the first time, to measure autophagy levels in diseases with a known link to autophagy, while also determining the contribution of autophagy to the efficacy of drugs. PMID- 22302010 TI - A supramolecular hydrogel containing boronic acid-appended receptor for fluorocolorimetric sensing of polyols with a paper platform. AB - A boronic acid-appended fluorescent receptor was incorporated into self-assembled nanofibers containing a hydrophobic FRET-paired dye to develop a gel-based fluorocolorimetric sensor for polyols. We demonstrated that the gel-based sensor is capable of detecting polyols such as catechol and dopamine not only under semi wet conditions, but also under dry conditions using a paper platform. PMID- 22302011 TI - Matrix metalloproteinase (MMP)-2 genetic variants modify the circulating MMP-2 levels in end-stage kidney disease. AB - BACKGROUND: Matrix metalloproteinases (MMPs) play important roles in the pathophysiology of renal diseases, and imbalanced MMP-2 and its endogenous inhibitor (the tissue inhibitor of metalloproteinases-2; TIMP-2) are implicated in the vascular alterations of end-stage kidney disease (ESKD) patients. We have examined whether MMP-2 gene polymorphisms and haplotypes modify MMP-2 and TIMP-2 levels in ESKD patients as well as the effects of hemodialysis on the concentrations of these biomarkers. METHODS: We determined MMP-2 and TIMP-2 plasma levels by gelatin zymography and ELISA, respectively, in 98 ESKD patients and in 38 healthy controls. Genotypes for two relevant MMP-2 polymorphisms (C( 1306)T and C(-735)T in the promoter region) were determined by TaqMan((r)) allele discrimination assay and real-time polymerase chain reaction. The software program PHASE 2.1 was used to estimate the haplotype frequencies. RESULTS: We found increased plasma MMP-2 and TIMP-2 levels in ESKD patients compared to controls (p < 0.05), and hemodialysis decreased MMP-2 (but not TIMP-2) levels (p < 0.05). The T allele for the C(-735)T polymorphism and the C-T haplotype were associated with higher MMP-2 (but not TIMP-2) levels (p < 0.05), whereas the C( 1306)T had no effects. Hemodialysis decreased MMP-2 (but not TIMP-2) levels independently of MMP-2 genotypes or haplotypes (p < 0.05). CONCLUSIONS: MMP-2 genotypes or haplotypes modify MMP-2 levels in ESKD patients, and may help to identify patients with increased MMP-2 activity in plasma. Hemodialysis reduces MMP-2 levels independently of MMP-2 genetic variants. PMID- 22302012 TI - Activation of the unfolded protein response is an early event in Alzheimer's and Parkinson's disease. AB - BACKGROUND: Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by the accumulation and aggregation of misfolded proteins. Disturbed homeostasis in the endoplasmic reticulum leads to accumulation of misfolded proteins, which triggers a stress response called the unfolded protein response (UPR) that protects the cell against the toxic buildup of misfolded proteins. OBJECTIVE: In this paper, we will briefly review the early involvement of the UPR in the pathology of AD and PD. METHODS: Expression of UPR activation markers was analyzed in human brain tissue using immunohistochemistry and Western blot analysis. RESULTS: Neuropathological studies demonstrate that UPR activation markers are increased in neurons in AD and PD. In AD, UPR activation markers are observed in neurons with diffuse staining of phosphorylated tau protein. In PD, increased immunoreactivity for UPR activation markers is detected in neuromelanin containing dopaminergic neurons of the substantia nigra, which colocalize with diffuse alpha-synuclein staining. CONCLUSION: UPR activation is closely associated with the first stages of accumulation and aggregation of the toxic proteins involved in AD and PD. Studies of postmortem brain tissue indicate that UPR activation is an early event in neurodegeneration. PMID- 22302013 TI - A study of quercetin effects on phospholipid membranes containing cholesterol using Laurdan fluorescence. AB - Quercetin (QCT) is an important bioactive natural compound found in numerous edible plants. Since the lipid bilayer represents an essential compound of the cell membrane, QCT's direct interaction with this structure is of great interest. Therefore, we proposed to study the effects of QCT on DMPC liposomes containing cholesterol (Chol), and for this purpose Laurdan fluorescence was used. As a fluorescent probe, Laurdan is able to detect changes in membrane phase properties. When incorporated in lipid bilayers, Laurdan emits from two different excited states, a non-relaxed one when the bilayer packing is tight and a relaxed state when the bilayer packing is loose. The main tool for quantifying QCT's effects on phospholipid membranes containing Chol has been the analysis, the decomposition of Laurdan emission spectra in sums of two Gaussian functions on energy. This kind of approach has allowed good analysis of the balance between the two emitting states of Laurdan. Our results show that both Laurdan emission states are present to different extents in a wide temperature range for DMPC liposomes with Chol. QCT is decreasing the phase transition temperature in pure DMPC liposomes as proved by generalized polarization (GP) values. QCT also quenches Laurdan fluorescence, depending on the temperature and the presence of Chol in the membrane. Stern-Volmer constants were calculated for different lipid membrane compositions, and the conclusion was that the relaxed state favors the nonradiative transitions of the fluorophore. PMID- 22302014 TI - Adjunctive therapy with pregabalin in generalized anxiety disorder patients with partial response to SSRI or SNRI treatment. AB - This study evaluated the efficacy of adjunctive pregabalin versus placebo for treatment of patients with generalized anxiety disorder (GAD) who had not optimally responded to previous or prospective monotherapies. This was a phase 3, randomized, double-blind, placebo-controlled study. Patients diagnosed with GAD who had a historical and current lack of response to pharmacotherapy [Hamilton Anxiety Rating Scale (HAM-A) of >= 22 at screening] were randomized to adjunctive treatment with either pregabalin (150-600 mg/day) or placebo. The primary outcome measure was the change in HAM-A total scores after 8 weeks of combination treatment. Adverse events were regularly monitored. Randomized patients (N=356) were treated with pregabalin (n=180) or placebo (n=176). Mean baseline HAM-A scores were 20.7 and 21.4, respectively. After treatment, the mean change in HAM A was significantly greater for pregabalin compared with placebo (-7.6 vs. -6.4, respectively; P<0.05). HAM-A responder rates (>= 50% reduction) were significantly higher for pregabalin (47.5%) versus placebo (35.2%; P=0.0145). The time-to-sustained response favored pregabalin over placebo (P=0.014). Adverse events were consistent with previous studies and discontinuations were infrequent for pregabalin (4.4%) and placebo (2.3%). The study was discontinued early after an interim analysis. The results indicate that adjunctive pregabalin is an efficacious therapy for patients with GAD who experience an inadequate response to established treatments. PMID- 22302015 TI - Time, evolution and physical reductionism. The arrow of evolutionary time challenges an eventual physical theory of everything. PMID- 22302017 TI - Influence of ligand field stabilization energy on the elastic properties of multiferroic MOFs with the perovskite architecture. AB - We report the mechanical properties of four isostructural metal-organic frameworks (MOFs) that adopt the ABX(3) perovskite topology: [(CH(3))(2)NH(2)]M(HCOO)(3), where M = divalent Mn, Co, Ni, and Zn. Their Young's moduli were measured via single-crystal nanoindentation. We show that the mechanical stability of such isostructural frameworks with octahedral coordination increases with greater ligand field stabilization energy (LFSE). PMID- 22302016 TI - Gene set analysis of survival following ovarian cancer implicates macrolide binding and intracellular signaling genes. AB - BACKGROUND: Genome-wide association studies (GWAS) for epithelial ovarian cancer (EOC), the most lethal gynecologic malignancy, have identified novel susceptibility loci. GWAS for survival after EOC have had more limited success. The association of each single-nucleotide polymorphism (SNP) individually may not be well suited to detect small effects of multiple SNPs, such as those operating within the same biologic pathway. Gene set analysis (GSA) overcomes this limitation by assessing overall evidence for association of a phenotype with all measured variation in a set of genes. METHODS: To determine gene sets associated with EOC overall survival, we conducted GSA using data from two large GWAS (N cases = 2,813, N deaths = 1,116), with a novel Principal Component-Gamma GSA method. Analysis was completed for all cases and then separately for high-grade serous histologic subtype. RESULTS: Analysis of the high-grade serous subjects resulted in 43 gene sets with P < 0.005 (1.7%); of these, 21 gene sets had P < 0.10 in both GWAS, including intracellular signaling pathway (P = 7.3 * 10(-5)) and macrolide binding (P = 6.2 * 10(-4)) gene sets. The top gene sets in analysis of all cases were meiotic mismatch repair (P = 6.3 * 10(-4)) and macrolide binding (P = 1.0 * 10(-3)). Of 18 gene sets with P < 0.005 (0.7%), eight had P < 0.10 in both GWAS. CONCLUSION: This research detected novel gene sets associated with EOC survival. IMPACT: Novel gene sets associated with EOC survival might lead to new insights and avenues for development of novel therapies for EOC and pharmacogenomic studies. PMID- 22302018 TI - Chrysophanol-8-O-glucoside, an anthraquinone derivative in rhubarb, has antiplatelet and anticoagulant activities. AB - Rhubarb is a widely used traditional medicine and has been reported to elicit a number of biological effects including anti-inflammatory and antiplatelet effects. In the present study, we investigated the effects of anthraquinone derivatives isolated from rhubarb on platelet activity. Of four anthraquinone derivatives isolated from rhubarb examined, chrysophanol-8-O-glucoside (CP-8-O glc) was found to have the most potent inhibitory effect on collagen- and thrombin-induced platelet aggregation. CP-8-O-glc-treated mice showed significantly prolonged bleeding times. Furthermore, CP-8-O-glc was found to have a significant inhibitory effect on rat platelet aggregation ex vivo and on thromboxane A(2) formation in vitro. In coagulation tests, CP-8-O-glc did not alter prothrombin time, and it prolonged the activated partial thromboplastin time. However, CP-8-O-glc only inhibited platelet phosphatidylserine exposure, but not exert direct inhibition on intrinsic factors. This study demonstrates the antiplatelet and anticoagulant effects of CP-8-O-glc and suggests that this compound might be of therapeutic benefit for the prevention of platelet-related cardiovascular diseases. PMID- 22302019 TI - Comparison of three tocopherol analogs as an inhibitor of production of proinflammatory mediators in macrophages. AB - Anti-inflammatory effects of tocopherol (TOL) analogs have been attributed to their potent antioxidant activities. However, we and others have separately reported that gammaTOL or alpha-tocopheryl succinate (alphaTOS), despite their lower antioxidant activities, inhibit lipopolysaccharide (LPS)-induced production of prostaglandin E(2) (PGE(2)) in macrophages and lung epithelial cells more effectively than alphaTOL. In the present study, we sought to directly analyze the effect of three TOL analogs (alphaTOL, alphaTOS, and gammaTOL) on LPS-induced production of pro-inflammatory mediators in macrophages. Our data demonstrated that the inhibitory effects of all three TOL analogs on nitric oxide production were very limited. In contrast, alphaTOS dose-dependently and significantly inhibited LPS-induced PGE(2) production in both RAW264.7 cells and peritoneal macrophages, whereas alphaTOL and gammaTOL were much less effective. Although alphaTOS had no effect on LPS-induced cyclooxygenase-2 expression, it did inhibit COX activity in intact cells. alphaTOS in combination with sulforaphane, a compound that blocked LPS-induced COX-2 expression, cooperatively and more significantly inhibited PGE(2) production. These findings suggest that alphaTOS is a more potent inhibitor of the pro-inflammatory mediator PGE(2). The inclusion of alphaTOS in vitamin supplements may further enhance the effectiveness of strategies for preventing diseases associated with inflammation. PMID- 22302020 TI - Synergistic interaction between fentanyl and a tramadol: paracetamol combination on the inhibition of nociception in mice. AB - Multimodal analgesic approaches to manage acute and chronic pain are commonly used in humans. Here, we attempted to characterize a synergistic interaction between fentanyl, tramadol, and paracetamol on the inhibition of nociception in a model of visceral pain in mice. The three-drug combined treatment displayed a potent synergistic antinociceptive effect, together with a significant reduction of gastrointestinal transit inhibition. Furthermore, selective u- and kappa opioid receptor antagonists reversed these synergistic antinociceptive effects, thus suggesting a pivotal role of the opioid system. Overall, this study presents accurate pre-clinical data that might be useful to improve the clinical management of opioid-mediated analgesia. PMID- 22302021 TI - Nicotine- and tar-free cigarette smoke induces cell damage through reactive oxygen species newly generated by PKC-dependent activation of NADPH oxidase. AB - We examined cytotoxic effects of nicotine/tar-free cigarette smoke extract (CSE) on C6 glioma cells. The CSE induced plasma membrane damage (determined by lactate dehydrogenase leakage and propidium iodide uptake) and cell apoptosis {determined by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) 2H-tetrazolium] reduction activity and DNA fragmentation}. The cytotoxic activity decayed with a half-life of approximately 2 h at 37 degrees C, and it was abolished by N-acetyl-L-cysteine and reduced glutathione. The membrane damage was prevented by catalase and edaravone (a scavenger of (*)OH) but not by superoxide dismutase, indicating involvement of (*)OH. In contrast, the CSE-induced cell apoptosis was resistant to edaravone and induced by authentic H(2)O(2) or O(2)(-) generated by the xanthine/xanthine oxidase system, indicating involvement of H(2)O(2) or O(2)(-) in cell apoptosis. Diphenyleneiodonium [NADPH oxidase (NOX) inhibitor] and bisindolylmaleimide I [BIS I, protein kinase C (PKC) inhibitor] abolished membrane damage, whereas they partially inhibited apoptosis. These results demonstrate that 1) a stable component(s) in the CSE activates PKC, which stimulates NOX to generate reactive oxygen species (ROS), causing membrane damage and apoptosis; 2) different ROS are responsible for membrane damage and apoptosis; and 3) part of the apoptosis is caused by oxidants independently of PKC and NOX. PMID- 22302022 TI - Chronic administration of nicotine-free cigarette smoke extract impaired endothelium-dependent vascular relaxation in rats via increased vascular oxidative stress. AB - Cigarette smoking has been implicated in the initiation and progression of cardiovascular disorders and atherosclerosis. Here, we examined the effects of nicotine-free cigarette smoke extract (CSE) on the regulation of cardiovascular function. Rats were subcutaneously administered PBS or nicotine-free CSE at 0.05 to 1.5 mL/day per rat for 4 weeks. Blood pressure, cardiac function, and vascular responsiveness were measured at 4 weeks after administration. Furthermore, acute effects of nicotine-free CSE were also studied in the aorta isolated from normal rats. Blood pressure and left ventricular systolic pressure (LVSP) were significantly increased in the nicotine-free CSE-administered rats, but heart rate, dP/dt(max), and dP/dt(min) were not affected. Endothelium-dependent relaxation by acetylcholine (ACh) in the nicotine-free CSE-treated rats was significantly attenuated compared to PBS-treated rats, but endothelium independent relaxation by sodium nitroprusside (SNP) did not differ. Pretreatment with superoxide dismutase restored the attenuated ACh-induced relaxation. Contractions by phenylephrine, angiotensin II, and KCl did not differ between two groups. In vitro acute nicotine-free CSE treatment did not alter the response to ACh or SNP. These results suggest that chronic nicotine-free CSE administration impairs endothelial function by increased production of superoxide derived from the vascular wall components other than smooth muscles and induces slight hypertension accompanied with LVSP elevation. PMID- 22302023 TI - Transient receptor potential vanilloid 1 - a polymodal nociceptive receptor - plays a crucial role in formaldehyde-induced skin inflammation in mice. AB - Formaldehyde (FA) is irritating to the skin and is the main cause of sick building syndrome. However, the cutaneous reaction induced by long-term FA exposure has not been fully investigated. In our previous study, we demonstrated that repeated painting of 2% - 10% FA on mouse ears caused marked ear swelling and increased mRNA expression of transient receptor potential vanilloid 1 (TRPV1) and neurotrophins in the ear. TRPV1 is reported to be involved in neurogenic inflammation; therefore, in the present study, we investigated the role of TRPV1 in FA-induced skin inflammation using TRPV1 gene-knockout mice. Mice were painted with 5% FA once a week for 5 weeks, and ear swelling and mRNA expression were investigated. Ear swelling and increased expression of neurotrophins mRNA by FA provocation in wild-type mice were attenuated by disruption of the TRPV1 gene. Furthermore, painting with a threshold dose of capsaicin, which does not induce ear swelling in intact mice, caused marked ear swelling after painting the ear 5 times with FA, indicating that inflamed tissues after FA application are hypersensitive to various ligands of TRPV1 in mice. These results demonstrated that neurogenic inflammation via TRPV1 and neurotrophins could be involved in FA induced dermatitis. PMID- 22302024 TI - Expression of microsomal prostaglandin E synthase-1 in the spinal cord in a transgenic mouse model of amyotrophic lateral sclerosis. AB - Prostaglandin E(2) (PGE(2)) is a key molecule involved in the neuroinflammatory processes that characterize amyotrophic lateral sclerosis (ALS). Although PGE(2) synthesis is regulated by PGE(2) synthases (PGESs), the pathological role of PGESs in ALS still remains unknown. Experiments were performed to elucidate the expression of PGESs and the localization of microsomal PGES-1 (mPGES-1) in neurons and glial cells in the spinal cord of ALS model (G93A) mice. Neurological symptom was observed in G93A mice from 14 weeks by the tail suspension test, and rotarod performances were decreased at 16 weeks and older. Western blotting revealed that the level of mPGES-1 was increased in G93A mice at 15 weeks and older. In contrast, the levels of cytosolic PGES and mPGES-2 did not change at any age. Immunohistochemical analysis demonstrated that age-dependent expression of mPGES-1 was found in motor neurons in G93A mice at 11 and 15 weeks. Immunoreactivity of mPGES-1 was also co-localized in Iba1-positive microglia in G93A mice at 15 weeks. These results suggest that mPGES-1 in motor neurons may play a role in the pathogenesis of ALS and that mPGES-1 may work sequentially in motor neurons and activated microglia to produce ALS symptoms in G93A mice. PMID- 22302025 TI - Tachyphylaxis to the sumatriptan-induced contractile effect in the human uterine artery but not in human cerebral blood vessels: pharmacological demonstration of the 5-HT(1B) receptor functionality loss. AB - The in vitro contractile response of the human uterine artery to sumatriptan was compared to that of human cerebral blood vessels. Artery rings were prepared for isometric contraction. Tachyphylaxis to the triptan-induced vascular contraction was observed in the uterine artery, but not in basilar and middle cerebral arteries. To evaluate 5-HT(1) receptor subtypes functionality, concentration response curves to sumatriptan were performed at 0 and 24 h after uterine artery isolation. Both 10 MUmol/l cyanopindolol and 63 nmol/l SB 224,289 (5-HT(1B) receptor antagonists) significantly antagonized the contractile response induced by sumatriptan at 0 h but not after 24 h of uterine artery isolation. The 5 HT(1B/1D) receptor antagonist BRL 15,572 at 10 MUmol/l significantly antagonized the sumatriptan contractile response at both experimental conditions. We conclude that the tachyphylaxis to sumatriptan observed in the non-cerebral blood vessels, and not in the cerebral ones, may be due to loss of functionality of the 5-HT(1B) receptor subtype, increasing the safety of triptans. PMID- 22302026 TI - Contrast-induced acute kidney injury: what is the prevalence of prevention protocols? PMID- 22302027 TI - Retracted article: Concomitant measurement of copeptin and high-sensitivity troponin for fast and reliable rule out of acute myocardial infarction. PMID- 22302028 TI - Renal bioenergetics during early gram-negative mammalian sepsis and angiotensin II infusion. AB - PURPOSE: To measure renal adenosine triphosphate (ATP) (bioenergetics) during hypotensive sepsis with or without angiotensin II (Ang II) infusion. METHODS: In anaesthetised sheep implanted with a renal artery flow probe and a magnetic resonance coil around one kidney, we induced hypotensive sepsis with intravenous Escherichia coli injection. We measured mean arterial pressure (MAP), heart rate, renal blood flow RBF and renal ATP levels using magnetic resonance spectroscopy. After 2 h of sepsis, we randomly assigned sheep to receive an infusion of Ang II or vehicle intravenously and studied the effect of treatment on the same variables. RESULTS: After E. coli administration, the experimental animals developed hypotensive sepsis (MAP from 92 +/- 9 at baseline to 58 +/- 4 mmHg at 4 h). Initially, RBF increased, then, after 4 h, it decreased below control levels (from 175 +/- 28 at baseline to 138 +/- 27 mL/min). Despite decreased RBF and hypotension, renal ATP was unchanged (total ATP to inorganic phosphate ratio from 0.69 +/- 0.02 to 0.70 +/- 0.02). Ang II infusion restored MAP but caused significant renal vasoconstriction. However, it induced no changes in renal ATP (total ATP to inorganic phosphate ratio from 0.79 +/- 0.03 to 0.80 +/- 0.02). CONCLUSIONS: During early hypotensive experimental gram-negative sepsis, there was no evidence of renal bioenergetic failure despite decreased RBF. In this setting, the addition of a powerful renal vasoconstrictor does not lead to deterioration in renal bioenergetics. PMID- 22302029 TI - Sepsis-induced acute kidney injury-is there a lack of energy? PMID- 22302030 TI - Autophagy--alias self-eating--appetite and ageing. PMID- 22302031 TI - Simplicity. PMID- 22302032 TI - alpha-Bridged BODIPY oligomers with switchable near-IR photoproperties by external-stimuli-induced foldamer formation and disruption. AB - We designed and synthesized a series of new alpha-bridged linear BODIPY oligomers, which exhibited strong absorption and high fluorescence efficiency in the near infrared region. The oligomers can be reversibly converted to the first NIR emissive BODIPY foldamers upon selective complexation with Cs(+). PMID- 22302034 TI - Evaluation of the performance of novel Abeta isoforms as theragnostic markers in Alzheimer's disease: from the cell to the patient. AB - BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disorder in the aging population and is characterized by extracellular plaques in the brain. The last decades have witnessed an explosion in studies of the role of amyloid-beta (Abeta) metabolism and aggregation in the pathogenesis of AD which has been translated into novel promising therapies with putative disease modifying effects. OBJECTIVE: The aim is to investigate the performance of truncated Abeta isoforms as theragnostic markers in clinical trials. METHODS: Abeta isoforms were immunoprecipitated from human, mouse and dog cerebrospinal fluid (CSF) or cell media and analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. RESULTS: Abeta1-14, Abeta1-15, and Abeta1-16 are elevated in cell media and in CSF in response to gamma-secretase inhibitor treatment. In a clinical trial including AD patients, Abeta1-14, Abeta1-15, and Abeta1-16 increased dose-dependently in response to treatment with the gamma-secretase inhibitor LY450139. In dogs, Abeta1-37 was significantly increased in response to treatment with the gamma-secretase modulator E2012. CONCLUSIONS: The results presented add to the current knowledge on APP processing and that Abeta isoforms can be used as novel biomarkers to monitor anti-Abeta treatments in clinical trials and may be valuable for making a go/no go decision for large and expensive phase 2 or 3 clinical trials. PMID- 22302033 TI - Multiple roles of cyclin-dependent kinase 4/6 inhibitors in cancer therapy. AB - BACKGROUND: Cyclin-dependent kinases (CDKs) regulate cell proliferation and coordinate the cell cycle checkpoint response to DNA damage. Although inhibitors with varying selectivity to specific CDK family members have been developed, selective CDK4/6 inhibitors have emerged as the most attractive antineoplastic agents because of the importance of CDK4/6 activity in regulating cell proliferation and the toxic effects associated with inhibition of other CDKs (eg, CDK1 and CDK2). METHODS: FVB/N wild-type mice (n = 13) were used to evaluate carboplatin-induced myelosuppression in bone marrow by complete blood cell counts after treatment with the CDK4/6 inhibitor PD0332991. Genetically engineered murine models of retinoblastoma (Rb)-competent (MMTV-c-neu) and Rb-incompetent (C3-TAg) breast cancer (n = 16 MMTV-c-neu mice in the carboplatin plus vehicle control group, n = 17 MMTV-c-neu mice in the carboplatin plus PD0332991 group, n = 17 C3-TAg mice in the carboplatin plus vehicle control group, and n = 14 C3-TAg mice in the carboplatin plus PD0332991 group) were used to investigate the antitumor activity of PD0332991 alone or in combination with chemotherapy. All statistical tests were two-sided. RESULTS: Coadministration of PD0332991 with carboplatin compared with carboplatin alone in FVB/N wild-type mice increased hematocrit (51.2% vs 33.5%, difference = 17.7%, 95% confidence interval [CI] = 26.7% to -8.6%, P < .001), platelet counts (1321 vs 758.5 thousand cells per MUL, difference = 562.5 thousand cells per MUL, 95% CI = -902.8 to -222.6, P = .002), myeloid cells (granulocytes and monocytes; 3.1 vs 1.6 thousand cells per MUL, difference = 1.5 thousand cells per MUL, 95% CI = -2.23 to -0.67, P < .001), and lymphocytes (7.9 vs 5.4 thousand cells per MUL, difference = 2.5 thousand cells per MUL, 95% CI = -4.75 to -0.18, P = .02). Daily administration of PD0332991 exhibited antitumor activity in MMTV-c-neu mice as a single agent. However, the combination of carboplatin plus PD0332991 decreased antitumor activity compared with carboplatin alone in Rb-competent mice (mean percent change in tumor volume at day 21 = -52.6% vs 3.7% for carboplatin and carboplatin plus PD0332991, respectively, difference = 56.3%, 95% CI = -109.0% to -3.6%, P = .04). In contrast, Rb-deficient tumors in C3-Tag mice were resistant to PD0332991, and coadministration of PD0332991 plus carboplatin had no effect on in vivo tumor growth (mean percent change in tumor volume at day 21 = 118.8% and 109.1% for carboplatin and carboplatin plus PD0332991, respectively, difference = 9.7%, 95% CI = -183.5% to 202.9%, P = .92). Finally, in tumor-bearing mice, coadministration of PD0332991 with carboplatin provided statistically significant protection of platelets (P = .04). CONCLUSION: We believe that the present data support a possible role for CDK4/6 inhibitors in a majority of patients with advanced cancer: to either inhibit tumor growth in CDK4/6-dependent tumors or ameliorate the dose-limiting toxicities of chemotherapy in CDK4/6-indepdendent tumors. Our data also suggest CDK4/6 inhibitors should not be combined with DNA damaging therapies, such as carboplatin, to treat tumors that require CDK4/6 activity for proliferation. PMID- 22302035 TI - Lyn kinase controls TLR4-dependent IKK and MAPK activation modulating the activity of TRAF-6/TAK-1 protein complex in mast cells. AB - Mast cells (MCs) control allergic reactions and contribute to protective innate immune responses through TLR4 activation. The tyrosine kinase Lyn is important to the high affinity IgE receptor (FcepsilonRI) signal transduction system in MCs, but its role on the TLR4 signalling cascade is still elusive. Here, we characterized several TLR4-triggered responses in bone marrow-derived mast cells (BMMCs) from wild-type (WT) and Lyn(-/-) mice. We found that Lyn(-/-) MCs secreted lower amounts of TNF-alpha after LPS challenge when compared with WT cells. Lyn(-/-) BMMCs showed less MAPK, IkappaB phosphorylation and NF-kappaB nuclear translocation after TLR-4 triggering than WT cells. LPS-induced MAPK and inhibitor of IkappaB kinase (IKK) phosphorylation were importantly reduced in the absence of Lyn. A constitutive interaction between TNF receptor associated factor 6 (TRAF-6) and phosphorylated TGF-beta-activated kinase (TAK-1) was observed in Lyn(-/-) BMMCs and this complex was insensitive to LPS addition. Lyn kinase was activated and associated to TRAF-6 shortly after LPS addition in WT MCs. Analyzing two local MC-dependent innate immune responses in vivo, we found that Lyn positively controls early TNF-alpha production and immune cell recruitment after an intraperitoneal injection of LPS. Our results indicate that Lyn plays a positive role in TLR4-induced production of TNF-alpha in MCs controlling the activity of the TRAF-6/TAK-1 protein complex. PMID- 22302037 TI - The relation between atherosclerosis and the occurrence of postoperative delirium in vascular surgery patients. AB - Old and frail patients undergoing vascular surgery seem at great risk of developing postoperative delirium (POD). The aim of this review was to identify risk factors for the development of POD in vascular surgery patients. Different aetiological factors have been identified, such as increased age, excessive blood transfusion, preoperative cognitive impairment and depression. Mounting evidence supports a role for inflammation and tobacco exposure in the development of POD. Vascular surgery patients differ from the general surgical population because they suffer from both loco-regional and systemic atherosclerosis. Although current scientific evidence cannot fully link both entities, evidence is growing that suggests a relationship between systemic and cerebrovascular atherosclerosis and the development of POD. PMID- 22302036 TI - Treatment of severe osteochondral defects of the knee by combined autologous bone grafting and autologous chondrocyte implantation using fibrin gel. AB - PURPOSE: Severe symptomatic and unstable osteochondral defects of the knee are difficult to treat. A variety of surgical techniques have been developed. However, the optimal surgical technique is still controversial. We present a novel technique in which autologous bone grafting is combined with gel-type autologous chondrocyte implantation (GACI). METHODS: Isolated severe osteochondral defects of the medial or lateral femoral condyle were treated by a two-step procedure. Firstly, chondrocytes were harvested during arthroscopy and cultured for 6 weeks. Secondly, a full thickness corticospongious autologuos bone graft, harvested from the medial or lateral femur condyle, is impacted in the defect and covered by GACI. The fibrin gel fills up to the exact shape of the chondral lesion and polymerizes within 3 min after application. RESULTS: From 2009 to 2011, 9 patients, median age 35 years (range 23-47), were treated by the combined autologous bone grafting and GACI technique. Median defect size was 7.1 cm2 (range 2.5-12.0), and median depth of the lesion was 0.9 cm (range 0.8-1.2). Median follow-up was 9 months (range 6-12 months). Six patients were available for 12-month follow-up. The mean IKDC score showed a 6-month improvement from 35 (SD +/- 16) to 51 (SD +/- 18) (n = 9; p = 0.01), and a 1-year improvement from 35 (SD +/- 16) to 57 (SD +/- 20) (n = 6; p = 0.03). The mean KOOS improved from 44 (SD +/- 16) to 62 (SD +/- 19) (n = 9; p = 0.07) at 6-month follow-up and from 44 (SD +/- 16) to 65 (SD +/- 24) (n = 6; p = 0.1) at 12-month follow-up. There was one failure that needed conversion to a unicompartmental knee arthroplasty. CONCLUSION: Combined autologous bone grafting and GACI may offer an alternative surgical option for severe and unstable osteochondral defects of the knee. PMID- 22302038 TI - The trochlear cleft: the "black line" of the trochlear trough. AB - OBJECTIVE: The "cartilage black line sign" is a recently described T2 dark cartilage lesion that we have identified appearing as a cleft in the trochlear trough. The purpose of our study was to define the MR imaging characteristics of a trochlear cleft, determine its incidence, and correlate the MR findings with arthroscopy. MATERIALS AND METHODS: A total of 1,300 consecutive MR examinations of the knee were retrospectively reviewed by consensus of two fellowship-trained musculoskeletal radiologists. The MR imaging characteristics and location of a trochlear cleft were determined. Imaging results were compared to arthroscopy when available. Patient age and gender were compared to 25 randomly selected control patients without trochlear clefts. RESULTS: A total of 25 (1.9%) individuals (11 females and 14 males; age range 19-45 years; mean age 28 years) were diagnosed with a trochlear cleft. The control group consisted of 11 females and 14 males; age range 19-83 years; mean age 46 years. Mean cleft length was 7 mm (range 6-12 mm); cleft location was consistently in the lower trochlear trough. No full-thickness cartilage defects were identified in the eight individuals in whom arthroscopic correlation was available. A grade 2 cartilage lesion was identified in a single individual; another progressed from grade 0 to a full-thickness trochlear lesion over an 8-month interval. Eight individuals were athletes. No significant difference in gender was noted between the two groups, however, the study group was significantly younger p < 0.0001. CONCLUSIONS: A trochlear cleft is a rare finding in young active individuals. It most likely indicates an incomplete cartilage fissure which may rarely progress to a full-thickness defect. PMID- 22302040 TI - Protective effect of amlodipine on rat bone tissue after orchidectomy. AB - AIM: Our study aimed to investigate the effect of amlodipine on bone metabolism in orchidectomized rats. METHODS: Eight-week-old rats were divided into three groups. The sham-operated control group (SHAM) and the control group after orchidectomy (ORX) received the standard laboratory diet (SLD). The experimental group after orchidectomy (ORX+AML) received SLD enriched with amlodipine for 12 weeks. Bone marker concentrations in serum of PINP, OPG and IGF-1, and the levels of CTX-I, BAP and BMP-2 in a bone homogenate were measured using enzyme-linked immunosorbent assay. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry. The femurs were used for biomechanical testing. RESULTS: Bone markers (CTX-I, BAP, BMP-2) in ORX were higher versus SHAM. In ORX+AML there was a decrease in PINP, CTX-I, BAP, BMP-2 and OPG versus ORX. IGF-1 was decreased in ORX versus SHAM. In ORX+AML it was increased versus ORX. In ORX, a decrease was demonstrated versus SHAM in BMD of the whole body, in the lumbar vertebrae and in both femurs. In ORX+AML there was an increase in BMD of the whole body versus ORX. Three-point bending test revealed a decrease in maximal load values in ORX versus SHAM. After amlodipine administration there was an increase in the left femur versus ORX. CONCLUSIONS: Amlodipine is capable of mitigating the negative effects of orchidectomy and could be a good prevention of osteoporosis. PMID- 22302041 TI - Angiotensin converting enzyme inhibitors mitigate collagen synthesis induced by a single dose of radiation to the whole thorax. AB - Our long-term goal is to use angiotensin converting enzyme (ACE) inhibitors to mitigate the increase in lung collagen synthesis that is induced by irradiation to the lung, which could result from accidental exposure or radiological terrorism. Rats (WAG/RijCmcr) were given a single dose of 13 Gy (dose rate of 1.43 Gy/min) of X-irradiation to the thorax. Three structurally-different ACE inhibitors, captopril, enalapril and fosinopril were provided in drinking water beginning 1 week after irradiation. Rats that survived acute pneumonitis (at 6-12 weeks) were evaluated monthly for synthesis of lung collagen. Other endpoints included breathing rate, wet to dry lung weight ratio, and analysis of lung structure. Treatment with captopril (145-207 mg/m(2)/day) or enalapril (19-28 mg/m(2)/day), but not fosinopril (19-28 mg/m(2)/day), decreased morbidity from acute pneumonitis. Lung collagen in the surviving irradiated rats was increased over that of controls by 7 months after irradiation. This increase in collagen synthesis was not observed in rats treated with any of the three ACE inhibitors. Analysis of the lung morphology at 7 months supports the efficacy of ACE inhibitors against radiation-induced fibrosis. The effectiveness of fosinopril against fibrosis, but not against acute pneumonitis, suggests that pulmonary fibrosis may not be a simple consequence of injury during acute pneumonitis. In summary, three structurally-different ACE inhibitors mitigate the increase in collagen synthesis 7 months following irradiation of the whole thorax and do so, even when therapy is started one week after irradiation. PMID- 22302042 TI - Dosage-dependent induction of behavioral decline in Caenorhabditis elegans by long-term treatment of static magnetic fields. AB - The aim of this work was to explore the molecular mechanisms associated with possible health hazards induced by static magnetic fields (SMFs). Nematodes were grown under SMFs at field strengths from 0 to 200 mT, and the speed of body movement was measured. The effects of exposure to static magnetic fields were observed to be significant in the higher field strength and longer treatment. To explore the possible molecular mechanisms responsible for these effects, semi quantitative real-time RT-PCR was performed using primers specific to 120 randomly selected genes. Twenty-six differentially expressed genes among apoptosis-, oxidative stress-, and cancer-related genes were identified, indicating that a global molecular response to SMF treatment occurred. The induction of apoptosis was verified by the increase of fluorescence in a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, by the caspase 3 activity assay, and by immunostaining using an antibody against the ced-3 gene product. Mutations in genes involved in major apoptotic pathways, that is, ced-3, ced-4, and ced-9, abolished this SMF-induced behavioral decline; this is consistent with the hypothesis that the apoptosis pathways are involved in the SMF-induced mobility decline. Here we show that long-term and low-dosage exposure to SMF is capable of inducing an apoptosis-mediated behavioral decline in nematodes. PMID- 22302043 TI - The metabolomic approach identifies a biological signature of low-dose chronic exposure to cesium 137. AB - Reports have described apparent biological effects of (137)Cs (the most persistent dispersed radionuclide) irradiation in people living in Chernobyl contaminated territory. The sensitive analytical technology described here should now help assess the relation of this contamination to the observed effects. A rat model chronically exposed to (137)Cs through drinking water was developed to identify biomarkers of radiation-induced metabolic disorders, and the biological impact was evaluated by a metabolomic approach that allowed us to detect several hundred metabolites in biofluids and assess their association with disease states. After collection of plasma and urine from contaminated and non contaminated rats at the end of the 9-months contamination period, analysis with a LC-MS system detected 742 features in urine and 1309 in plasma. Biostatistical discriminant analysis extracted a subset of 26 metabolite signals (2 urinary, 4 plasma non-polar, and 19 plasma polar metabolites) that in combination were able to predict from 68 up to 94% of the contaminated rats, depending on the prediction method used, with a misclassification rate as low as 5.3%. The difference in this metabolic score between the contaminated and non-contaminated rats was highly significant (P = 0.019 after ANOVA cross-validation). In conclusion, our proof-of-principle study demonstrated for the first time the usefulness of a metabolomic approach for addressing biological effects of chronic low-dose contamination. We can conclude that a metabolomic signature discriminated (137)Cs-contaminated from control animals in our model. Further validation is nevertheless required together with full annotation of the metabolic indicators. PMID- 22302044 TI - SirT1 confers hypoxia-induced radioresistance via the modulation of c-Myc stabilization on hepatoma cells. AB - Intratumoral hypoxia is an important contributory factor to tumor cell resistance to radiotherapy. SirT1, a nicotinamide adenine dinucleotide (NAD(+))-dependent histone/protein deacetylase, has been linked to the decrease of radiation-induced DNA damage and seems to be critical for cancer therapy. The purpose of this study was to investigate the role of SirT1 in hypoxia-induced radiation response on hepatoma cells. It was found that the administration with resveratrol, a putative SirT1 activator, enhanced the resistance of HepG2 cells against radiation-induced DNA damage of MN formation under hypoxia condition; while nicotinamide, a well known SirT1 inhibitor, sensitized this radiation damage. Nevertheless, pretreatment of cells with 10058-F4, a specific inhibitor of c-Myc, almost eliminated the nicotinamide-induced radiosensitive effect. Further studies revealed that resveratrol inhibited c-Myc protein accumulation via up-regulation of SirT1 expression and deacetylase activity, and this loss of c-Myc protein was abolished by inhibiting its degradation in the presence of MG132, a potent inhibitor of proteasome. In contrast, nicotinamide attenuated c-Myc protein degradation induced by radiation under hypoxia through inhibition of SirT1 deacetylase activity. Our findings suggest that SirT1 could serve as a novel potent target of radiation-induced DNA damage and thus as a potential strategy to advance the efficiency of radiation therapy in hepatoma entities. PMID- 22302045 TI - Heavy ions can enhance TGFbeta mediated epithelial to mesenchymal transition. AB - TGFbeta is a key modulator of the Epithelial-Mesenchymal Transition (EMT), a process important in cancer progression and metastasis, which leads to the suppression of epithelial genes and expression of mesenchymal proteins. Ionizing radiation was found to specifically induce expression of the TGF-beta1 isoform, which can modulate late post-radiation changes and increase the risk of tumor development and metastasis. Interactions between TGFbeta induced EMT and DNA damage responses have not been fully elucidated, particularly at low doses and following different radiation quality exposures. Further characterization of the relationship between radiation quality, EMT and cancer development is warranted. We investigated whether space radiation induced TGFbeta dependent EMT, using hTERT immortalized human esophageal epithelial cells (EPC2-hTERT) and non transformed mink lung epithelial cells (Mv1Lu). We have observed morphologic and molecular alterations in EPC2 and Mv1Lu cells consistent with EMT after pre treatment with TGFbeta1. This effect could be efficiently inhibited in both cell lines by the use of a TGFbetaRI inhibitor. High-energy silicon or iron nuclei were each able to cause a mild induction of EMT, with the inclusion of TGFbeta1 inducing a greatly enhanced EMT phenotype even when cells were irradiated with doses as low as 0.1 Gy. A further enhancement of EMT was achieved at a higher dose of 2 Gy. TGFbetaRI inhibitor was able to reverse the EMT induced by the combination of TGFbeta1 and radiation. These studies indicate that heavy ions, even at a low dose, may trigger the process of TGFbeta1-induced EMT, and suggest further studies are needed to determine whether the chronic exposures received in space may potentiate this process in astronauts, leading to an increased risk of cancer. PMID- 22302046 TI - Mitochondria-targeted superoxide dismutase (SOD2) regulates radiation resistance and radiation stress response in HeLa cells. AB - Reactive oxygen species (ROS) act as a mediator of ionizing radiation-induced cellular damage. Previous studies have indicated that MnSOD (SOD2) plays a critical role in protection against ionizing radiation in mammalian cells. In this study, we constructed two types of stable HeLa cell lines overexpressing SOD2, HeLa S3/SOD2 and T-REx HeLa/SOD2, to elucidate the mechanisms underlying the protection against radiation by SOD2. SOD2 overexpression in mitochondria enhanced the survival of HeLa S3 and T-REx HeLa cells following gamma irradiation. The levels of gammaH2AX significantly decreased in HeLa S3/SOD2 and T-REx HeLa/SOD2 cells compared with those in the control cells. MitoSox(TM) Red assays showed that both lines of SOD2-expressing cells showed suppression of the superoxide generation in mitochondria. Furthermore, flow cytometry with a fluorescent probe (2',7'-dichlorofluorescein) revealed that the cellular levels of ROS increased in HeLa S3 cells during post-irradiation incubation, but the increase was markedly attenuated in HeLa S3/SOD2 cells. DNA microarray analysis revealed that, of 47,000 probe sets analyzed, 117 and 166 probes showed more than 2-fold changes after 5.5 Gy of gamma-irradiation in control and HeLa S3/SOD2 cells, respectively. Pathway analysis revealed different expression profiles in irradiated control cells and irradiated SOD2-overexpressing cells. These results indicate that SOD2 protects HeLa cells against cellular effects of gamma-rays through suppressing oxidative stress in irradiated cells caused by ROS generated in the mitochondria and through regulating the expression of genes which play a critical role in protection against ionizing radiation. PMID- 22302047 TI - Overexpression of Cks1 increases the radiotherapy resistance of esophageal squamous cell carcinoma. AB - PURPOSES: The Cks1 protein is a member of the highly conserved family of Cks/Suc1 proteins, which interact with Cdks, and was found to be an essential cofactor for efficient Skp2-dependent ubiquitination of p27. The present study was undertaken to examine the expression status of Cks1 in esophageal squamous cell carcinoma and its significance. MATERIALS AND METHODS: The expression of Cks1 in 140 esophageal squamous cell carcinoma patients was examined by immunohistochemistry. The correlations between Cks1 expression and tumor clinicopathologic features were analyzed. The effects of Cks1 expression on radiotherapy results were also examined. RESULTS: In the present study, we found that Cks1 is overexpressed in esophageal squamous cell carcinoma tissues. Elevated expression of Cks1 correlates significantly with tumor stage and positive lymph node metastasis (p < 0.05). Moreover, a significant negative correlation was found between Cks1 expression and the survival of patients who received radiotherapy (p < 0.05). At the molecular level, forced expression of Cks1 promotes the radio-resistance ability of EC9706 cells. Knockdown of Cks1 expression sensitizes cancer cells to radiation, and a wobble mutant of Cks1 that is resistant to Cks1 siRNA can rescue this effect. CONCLUSIONS: These results demonstrate for the first time that overexpression of Cks1 correlates with the increased radiotherapy resistance of esophageal squamous cell carcinoma. PMID- 22302048 TI - Extremely low frequency magnetic fields do not elicit oxidative stress in MCF10A cells. AB - The aim of this study was to determine whether extremely low frequency magnetic fields (ELF-MF) could affect intracellular reactive oxygen species (ROS) levels and antioxidant enzyme activity. After MCF10A human breast epithelial cells were exposed to 1 mT of 60 Hz ELF-MF for 4 hours, intracellular ROS level, superoxide dismutase (SOD) activity, and reduced to oxidized glutathione (GSH/GSSG) ratio were measured. The cells exposed to ELF-MF did not evidence statistically significant changes in the above-mentioned biological parameters as compared to either the incubator controls or sham-exposed cells. By way of contrast, the IR exposed cells exhibited marked changes in ROS level, SOD activity, and GSH/GSSG ratio. When we assessed morphological changes and senescence-associated beta galactosidase (SA-beta-Gal) activity, only the IR-exposed cells were positive. According to our results, it could be concluded that ELF-MF has no effect on intracellular ROS level, SOD activity, and GSH/GSSG ratio under our exposure condition. PMID- 22302049 TI - Evaluation of the relative biological effectiveness of carbon ion beams in the cerebellum using the rat organotypic slice culture system. AB - To clarify the relative biological effectiveness (RBE) values of carbon ion (C) beams in normal brain tissues, a rat organotypic slice culture system was used. The cerebellum was dissected from 10-day-old Wistar rats, cut parasagittally into approximately 600-um-thick slices and cultivated using a membrane-based culture system with a liquid-air interface. Slices were irradiated with 140 kV X-rays and 18.3 MeV/amu C-beams (linear energy transfer = 108 keV/um). After irradiation, the slices were evaluated histopathologically using hematoxylin and eosin staining, and apoptosis was quantified using the TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay. Disorganization of the external granule cell layer (EGL) and apoptosis of the external granule cells (EGCs) were induced within 24 h after exposure to doses of more than 5 Gy from C-beams and X-rays. In the early postnatal cerebellum, morphological changes following exposure to C-beams were similar to those following exposure to X-rays. The RBEs values of C-beams using the EGL disorganization and the EGC TUNEL index endpoints ranged from 1.4 to 1.5. This system represents a useful model for assaying the biological effects of radiation on the brain, especially physiological and time-dependent phenomena. PMID- 22302050 TI - Experimental model of naturally occurring post-radiation sarcoma: interest of positron emission tomography (PET) for early detection. AB - Radiotherapy is an integral part of overall cancer therapy. One of the most serious adverse effects of irradiation concern, for long-term survivors, the development of post-radiation sarcoma (PRS) in healthy tissues located within the irradiated area. PRS have bad prognosis and are often detected at a late stage. Therefore, it is obvious that the early detection PRS is a key-point and the development of preclinical models is worthy to evaluate innovative diagnostic and therapeutic procedures. The aim of this study was to develop a spontaneous rodent model of PRS and to evaluate the potency of Positron Emission Tomography (PET) for early detection. Fifteen Wistars rats were irradiated unilateraly on the hindlimb with a single dose of 30 Gy. Sequential analysis was based on observational staging recordings, Computerized Tomography (CT) scanning and PET. Tumors were removed and, histopathological and immunochemistry analyses were performed. Among the irradiated rats, 12 sarcomas (80%) were detected. All tumors occurred naturallty within the irradiated hindlimb and were highly aggressive since most tumors (75%) were successfully transplanted and maintained by serial transplantation into nude mice. Upon serial staging recordings, using PET, was found to enable the detection of PRS earlier after irradiation than with the other methods (i.e. 11.9 +/- 1.8 vs 12.9 +/- 2.6 months). These results confirmed the interest of experimental models of PRS for the preclinical evaluation of innovative diagnostic strategies and confirmed the potency of PET for early detection of PRS. This preclinical model of PRS can also be proposed for the evaluation of therapeutic strategies. PMID- 22302051 TI - Association of computed tomography-detected pulmonary interstitial changes with severe radiation pneumonitis for patients treated with thoracic radiotherapy. AB - We evaluated associations of interstitial changes with radiation pneumonitis (RP) for patients treated with thoracic radiotherapy. Between 2005 and 2009, patients who received thoracic radiotherapy of 40 Gy or more for lung cancer or thymic tumors and were followed-up for more than 6 months were eligible for this study. Possible risk factors for RP included the presence of interstitial changes on computed tomography before radiotherapy, and elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels; these were compared with the incidences of severe RP. A total of 106 patients were included. The incidences of RP were 4 (4%), 0 (0%), and 5 (5%) for grades 3, 4, and 5, respectively. For those with interstitial changes, the incidence of RP >= grade 3 was significantly increased from 3% (2/79) to 26% (7/27) (p < 0.001). CRP and LDH levels were also associated with increased RP, as were pulmonary emphysema and performance status >= 2. Among 91 patients with RP >= grade 1, RP grade >= 3 occurred significantly earlier than grades 1 and 2. In conclusion, pulmonary interstitial changes, LDH and CRP levels, pulmonary emphysema, and performance status >= 2 were significantly associated with RP >= grade 3. RP grade >= 3 occurred significantly earlier than grades 1 and 2. The early appearance of interstitial changes requires careful management due to the possibility of severe RP. PMID- 22302052 TI - Retinoblastoma 94 enhances radiation treatment of esophageal squamous cell carcinoma in vitro and in vivo. AB - We performed the study to investigate whether adenovirus-mediated retinoblastoma 94 (RB94) gene transfer could enhance radiation treatment of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. ESCC cells (Kyse150 cell line) were cultivated in vitro and tumors originated from the cell line were propagated as xenografts in nude mice. Treatment with Ad-RB94 and/or ionizing radiation (IR) was carried out both in vitro and in vivo with Ad-LacZ control vector and blank control. Cell viability, cell cycle distribution, cell apoptosis, tumor growth and transfected gene expression were evaluated and tumor degeneration was analyzed. The data of quantification real-time PCR assays and immunohistochemistry staining using RB antibody indicated that RB94 was efficiently transfected into Kyse150 cells. In vitro, data of cell growth assay indicated that treatment with Ad-RB94 improved radiation treatment of Kyse150 cells. Tumor xenograft studies, pathological analysis of H.E. staining and Ki67 staining suggested transfecting RB94 enhanced tumor regression induced by radiation treatment in vivo. In addition, data of Annexin V, TUNEL and cell cycle distribution assays proposed combination treatment effectively induced cell apoptosis and cell cycle arresting in G2/M phase. In conclusion, transferring RB94 gene by the adenoviral vector enhances radiation treatment of ESCC. PMID- 22302053 TI - The clinical characteristic differences between thrombosis-related edema and lymphedema following radiotherapy or chemoradiotherapy for patients with cervical cancer. AB - Thrombosis-related edema and lymphedema are two principal types of lower extremity edema results from radiotherapy alone or chemoradiotherapy for patients with cervical cancer. To characterize differences between them, a retrospective study was performed. We collected data including age, race, body weight, FIGO stage, histology type, platelet count, haemoglobin, time of definitely diagnosis, therapeutic regimen, edema type and which leg edema firstly occurred in. Of 40 patients who were eligible for this study, 32 were diagnosed as thrombosis related edema and 8 diagnosed as lymphedema. The differences in patient age (p = 0.004), propotion of race (p = 0.021), the latent time (p = 0.002) and the mean platelet count (p = 0.019) were statistically significant. Among 32 patients with thrombosis-related edema, 34.4% were in stage II and 53.1% in stage III, 78.1% were squamous cell carcinoma. Among 8 patients with lymphedema, 87.5% were in stage II and 62.5% were squamous cell carcinoma. The differences were not statistically significant for weight (p = 0.94), histology type (p = 0.648), edema site (p = 0.236), haemoglobin (p = 0.088) between the two grouping patients. Although the small patient cohort is a limitation, the results suggest that the patients with thrombosis-related edema may have higher proportion, lower age, shorter latent edema time and more platelet count than those with lymphedema. Also, thrombosis-related edema was likely inclined to Uigur and lymphedema to Han race. We did not find statistical differences in weight, edema site, histology type and haemoglobin between patients with thrombosis-related edema and lymphedema. PMID- 22302054 TI - Evaluation of parotid gland function using equivalent cross-relaxation rate imaging applied magnetization transfer effect. AB - Safe imaging modalities are needed for evaluating parotid gland function. The aim of this study was to validate the utility of a magnetic resonance imaging (MRI) tool, equivalent cross-relaxation rate imaging (ECRI), as a measurement of parotid gland function after chemoradiotherapy. Subjects comprised 18 patients with head-neck cancer who underwent ECRI and salivary gland scintigraphy. First, we calculated ECR values (signal intensity on ECRI), maximum uptake rate (MUR) and washout rate (WOR) from salivary gland scintigraphy data at the parotid glands. Second, we investigated correlations between ECR values and each parameter of MUR (uptake function) and WOR (secretory function) obtained by salivary gland scintigraphy at the parotid gland. Next, we investigated each dose response for ECR, MUR and WOR at the parotid gland. A correlation was detected between ECR values and MUR in both the pre- (r = -0.55, p < 0.01) and post treatment (r = -0.50, p < 0.05) groups. A significant post-treatment correlation was detected between the percentage change in ECR values at 3-5 months after chemoradiotherapy and median dose to the parotid gland (Pearson correlation, r = 0.62, p < 0.05). However, no correlations were detected between median dose to the parotid gland and either MUR or WOR. ECRI is a new imaging tool for evaluating the uptake function of the parotid gland after chemoradiotherapy. PMID- 22302055 TI - Involvement of intracellular reactive oxygen species and mitochondria in the radiosensitivity of human hematopoietic stem cells. AB - Reactive oxygen species (ROS) can cause significant biological damage and are produced from low linear energy transfer-ionizing radiation, such as X-rays. Although hematopoietic stem cells (HSCs) are known to be particularly sensitive to ionizing radiation, little is known about the roles of mitochondria and ROS production in determining the radiosensitivity of HSCs. The clonogenic survival of CD34(+) HSCs, intracellular mitochondrial content, and intracellular ROS production after irradiation were investigated to elucidate the involvement of mitochondria and ROS in the individual radiosensitivity of HSCs detected in human placental/umbilical cord blood. The results showed that large individual differences exist in the initial numbers of each progenitor cell type, as well as in the surviving fraction of cells. When supplemented with an appropriate cytokine combination, a statistically significant increase in ROS production was observed at 3 h after 2 or 4 Gy of irradiation (P < 0.05), with nearly a return to initial levels by 6 h. In contrast, no significant difference was observed under cytokine-free conditions. At this stage, no significant correlations were observed between ROS production, intracellular mitochondrial content, and the surviving fractions of each HSC progenitor. These results suggest that the kinetics of ROS generation during the 6 h after ionizing radiation have little effect on the different radiation sensitivity of HSCs. PMID- 22302056 TI - Areal differences in diameter and length of corticofugal projections. AB - Cortical areas differ in the size and distribution of neuronal cell bodies, density, and distribution of myelinated axons, connections, and functional properties. We find that they also differ in the diameter of long corticofugal axons, with the thickest axons originating from primary motor, somatosensory, and visual areas and the thinnest ones from prefrontal and temporal areas. Since diameter is proportional to axonal conduction velocity, it can be inferred that action potentials issued from the different areas will be relayed to their targets at different speed. Conduction delays also depend on conduction distance. By computing conduction velocity and conduction distances, we found the longest conduction delays for the primary visual and temporal areas and the shortest for the premotor, primary motor, and somatosensory areas, compatible with the available electrophysiological data. These findings seem to establish a new principle in cortical organization relevant to the pathophysiology of neurological or psychiatric illnesses as well as to the speed of information processing in cortical circuits. PMID- 22302057 TI - Reduction of tinnitus severity by the centrally acting muscle relaxant cyclobenzaprine: an open-label pilot study. AB - Tinnitus, the phantom perception of sounds, is a highly prevalent disorder. Although a wide variety of drugs have been investigated off label for the treatment of tinnitus, there is no approved pharmacotherapy. We report an open label exploratory pilot study to assess the effect of muscle relaxants acting on the central nervous system on tinnitus patients. Cyclobenzaprine at high (30 mg) and low doses (10 mg), orphenadrine (100 mg), tizanidine (24 mg) and eperisone (50 mg) were administered to a maximum of 20 patients per group over a 12-week period. High-dose cyclobenzaprine resulted in a significant reduction in the Tinnitus Handicap Inventory (THI) score between baseline and week 12 in the intention-to-treat sample. On the other hand, other treatments were not effective. These results were confirmed in an explorative analysis where baseline corrected THI and Clinical Global Impression scores at week 12 were compared between groups. The present open trial presents a new promising pharmacotherapy for tinnitus that should be validated in placebo-controlled double-blind trials. PMID- 22302058 TI - Higher DEFB4 genomic copy number in SLE and ANCA-associated small vasculitis. AB - OBJECTIVE: Evidence shows that defensins are involved in the pathogenesis of SLE and ANCA-associated small vasculitis (AASV). The copy number variation of DEFB4 has been proposed to be susceptible to inflammatory disorders. This study aims to investigate whether the DEFB4 genomic copy number variations associate with the susceptibility to these two autoimmune diseases. METHODS: A total of 1178 Chinese people were enrolled, including panel 1 comprising 240 SLE patients and 275 matched controls, panel 2 comprising 303 SLE patients and 248 matched controls and panel 3 with 112 AASV patients. The DEFB4 copy number was typed by a paralogue ratio test (PRT), and all the subjects in panel 1 were also typed using the restriction enzyme digest variant ratio (REDVR) for validation. RESULTS: The results from PRT and REDVR were highly concordant (R = 0.911, P = 3.85 * 10( 199)) and allowed copy numbers to be assigned into integer classes with high confidence. Comparison of mean DEFB4 copy number revealed a small increase in cases with SLE both in Panel 1 (P = 0.063) and Panel 2 (P = 0.017). When pooling panels 1 and 2 together, the association was reinforced (P = 0.002) in SLE. Such association was also observed in AASV (P = 0.009). CONCLUSION: We found that a higher DEFB4 gene copy number was associated with both SLE and AASV. PMID- 22302059 TI - The provisional ACR/EULAR definition of remission in RA: a comment on the patient global assessment criterion. AB - OBJECTIVES: The provisional ACR/European League Against Rheumatism (EULAR) definition of remission in RA requires a score of <=1 on the patient global assessment (PGA, 0-10 scale). We explored the relation between the PGA criterion and the patient's clinical disease state in an observational dataset. METHODS: Data of 512 newly diagnosed RA patients of the Dutch Rheumatoid Arthritis Monitoring (DREAM) remission induction cohort were analysed. Both 28-joint counts and more comprehensive joint counts (tender joint count-53, swollen joint count 44) were used. RESULTS: ACR/EULAR remission was present in 20.1% of the patients when using 28-joint counts and in 17.4% of the patients when applying more comprehensive joint counts. In 108 patients, the PGA score was >1 despite fulfilment of the remaining criteria (TJC28, SJC28 and CRP in mg/dl <=1). Residual disease activity was observed in 31.5% (34/108) and median (interquartile range) scores on PGA, pain and fatigue were 2.4 (1.8-4.0), 2.0 (1.1-3.0) and 2.7 (1.3-5.0), respectively. Applying more comprehensive joint counts showed comparable results. In 19.5% (100/512) of patients, disease activity was absent (TJC53 = 0, SJC44 = 0, and CRP <=1). In 41% (n = 41) of these patients, the PGA score was >1. Receiver operating characteristic analysis showed moderate accuracy of the PGA to discriminate between fulfilment and no fulfilment of all remaining criteria. CONCLUSION: Frequently, patients did not meet the PGA criterion despite a good clinical disease state. Apparently the PGA is not solely influenced by RA disease activity. In patients with marked divergence between the PGA and objective clinical measurements, caution should be taken when applying the provisional ACR/EULAR definition of remission. PMID- 22302060 TI - IL-7 drives Th1 and Th17 cytokine production in patients with primary SS despite an increase in CD4 T cells lacking the IL-7Ralpha. AB - OBJECTIVE: To study the phenotypic characteristics of and the balance between systemic IL-7 receptor (IL-7R)alpha+ and IL-7Ralpha- Tregs in primary SS (pSS) patients as compared with control subjects and to assess the functional consequences this has for (IL-7-induced) T-cell activation. METHODS: The functional properties of IL-7Ralpha+ and IL-7Ralpha- (CD25+) CD4 T cells from pSS patients were tested in vitro. Expression of CD25 and FoxP3 by IL-7Ralpha+ and IL 7Ralpha- CD4 T cells from pSS patients and healthy controls (HCs) were assessed. Also, the net ex vivo T-cell cytokine production and the capacity of IL-7 to activate total CD4 T cells from pSS patients compared with HCs in vitro was tested. RESULTS: IL-7Ralpha+ T cells from pSS patients strongly proliferated and their numbers were slightly reduced compared with HCs. This reduced number was caused by an increase in both anergic and suppressive IL-7Ralpha- CD25+ T cells expressing high levels of FoxP3, but also by increases in IL-7Ralpha- CD25- CD4 T cells that only moderately expressed FoxP3. This altered balance in IL-7Ralpha+ and IL-7Ralpha- CD4 T cells was accompanied by unchanged ex vivo Th1, Th2 and Th17 cytokine production of total CD4 T cells. Furthermore, the increased numbers of IL-7Ralpha- CD25+ T cells did not prevent specific IL-7-induced Th1 and Th17 cytokine production by IL-7Ralpha+ T cells. CONCLUSION: IL-7Ralpha+ cells are highly proliferating cells that respond strongly to IL-7 despite an increased number of IL-7Ralpha- T cells that express FoxP3 and CD25. The recent finding that IL-7 and IL-7Ralpha+ T cells were both found to be increased in exocrine glands of pSS patients indicates that IL-7 could contribute to glandular inflammation by activation of IL-7Ralpha+ responder T cells despite the increased numbers of Tregs. PMID- 22302061 TI - Ultrasonography of major salivary glands could be an alternative tool to sialoscintigraphy in the American-European classification criteria for primary Sjogren's syndrome. AB - OBJECTIVE: To test the diagnostic accuracy of modified American-European classification criteria (AEC) for primary SS (pSS) by replacing sialoscintigraphy (sSC) with ultrasonography of the major salivary glands. METHODS: One hundred and ninety subjects were evaluated for the diagnosis of pSS, including US of the salivary glands. We tested the diagnostic accuracy of the three different sets of five diagnostic criteria for pSS. Each set combined these four criteria (ocular symptoms, oral symptoms, Schirmer-I test and auto-SS-A antibody) and one of the following: US (US set), sSC (sSC set) or biopsy (Biopsy set). The area under the receiver operating characteristics curve (AUC-ROC) was used to evaluate the diagnostic accuracy of each set of criteria. RESULTS: Out of 190 subjects examined, 140 subjects fulfilled the AEC for the diagnosis of pSS, whereas 50 subjects were classified as non-pSS subjects. US score was positive in 129 (92%), sSC in 123 (88%) and biopsy in 93 (66%) of 140 pSS patients. Among 140 patients with pSS, 88 (63%) patients fulfilled the criteria of the US set, 85 (61%) patients of the sSC set and 71 (51%) patients of the Biopsy set. None of the subjects from the non-pSS group fulfilled any of the sets of criteria. Diagnostic accuracy of each of the three sets of criteria was high and similar [AUC-ROC (s.e.) for the US set was 0.99 (0.00), followed by the sSC set at 0.98 (0.00) and the Biopsy set at 0.97 (0.00)]. CONCLUSION: US finding of major salivary gland involvement could replace sSC in AEC for the diagnosis of pSS. PMID- 22302062 TI - Cyclodiode laser in the treatment of acute angle closure. AB - AIM: To describe the outcome of using diode laser transscleral cyclophotocoagulation (cyclodiode laser) as a safe technique in managing acute angle closure refractory to conventional treatment. METHODS: This is a retrospective case series from two ophthalmic units in the United Kingdom. Five patients with acute angle closure refractory to medical and laser treatment underwent cyclodiode laser treatment. Demographic information, symptoms, medical and surgical treatment, visual outcomes, and intraocular pressure (IOP) control were recorded. CASE REPORTS: All five patients had symptomatic acute angle closure. Conventional management, including topical and systemic medical treatment, laser iridotomy and laser iridoplasty, did not achieve adequate IOP control or relieve symptoms. Emergency cyclodiode laser treatment was performed within 2-23 days of presentation. All patients subsequently required lensectomy at a later date. At final follow-up (6-14 months), all patients had visual acuity of 6/12 or better with well-controlled IOPs (<= 17 mm Hg). Only one patient was on topical treatment. One patient developed a persistent low-grade anterior uveitis. DISCUSSION: Cyclodiode laser is a safe alternative to emergency lensectomy or trabeculectomy in cases of acute angle closure, which do not respond to treatment. PMID- 22302063 TI - Diabetic retinopathy equity profile in a multi-ethnic, deprived population in Northern England. AB - PURPOSE: Equity profiles are an established public health tool used to systematically identify and address inequity within health and health services. Our aim was to conduct an equity profile to identify inequity in eye health across Leeds and Bradford. This paper presents results of findings for diabetic retinopathy in Bradford and Airedale. METHODS: A variety of routine health data were included and sub-analysed by measures of equity, including age, sex, ethnicity, and deprivation to identify inequity in eye health and healthcare. The Spearman Rank Correlation Coefficient was used to determine the association between variables. RESULTS: The prevalence of diagnosed diabetes in Bradford and Airedale district is 6.6% compared to 4.3% in nearby Leeds and 5.1% nationally. The age-standardised prevalence of diagnosed diabetic retinopathy within Bradford and Airedale is 2.21% (95% CI 1.54-2.26%), with a disproportionately high prevalence of disease in the Pakistani population and the most deprived parts of the population. There was a poorer uptake of diabetic retinopathy screening in more deprived parts of the district and the proportions with a higher rate of referral to ophthalmology following the screening in Black and Minority Ethnic populations compared with the white population (13.2% vs 6.9%). Uptake of secondary care outpatient appointments is much lower in more deprived populations. CONCLUSION: Inequalities are inherent in diabetic retinopathy prevalence, diagnosis, and treatment. The reasons for these inequities are multi factorial and further investigation of reasons for poor uptake of services is required. Addressing the inequalities in eye health and healthcare requires cross organisational collaboration. PMID- 22302064 TI - Consent for cataract surgery training: a national trainers' survey. AB - AIMS: To evaluate current trainers' attitudes and practices for informing patients about the trainee participation in cataract surgery within the United Kingdom. METHODS: An anonymous online survey was distributed to current cataract surgery trainers via all Royal College of Ophthalmologists' tutors within the United Kingdom. Trainers were asked specific questions about their current consent practice regarding trainee participation in the cataract surgery. Questions also targeted experiences of patient complaints about training. RESULTS: One hundred and twenty-three trainers completed the survey. Ninety-three percent (n=114) of responders were consultants and 7% (n=8) were non-consultant career-grade doctors or other grades. A total of 34% (n=42) of responders stated that consent was usually taken by themselves or the trainee assigned to the list, whereas 26% (n=32) always took consent themselves. Sixty percent of responders (n=74) stated that consent is taken on the day of surgery; 59% (n=73) indicated consent is taken where listing takes place. Thirty-three percent (n=41) of trainers indicated that they had experienced patient dissatisfaction or complaints. Surgical complications, length of surgery, and discussions during surgery were the leading causes of complaints. Thirty-nine percent (n=48) would operate themselves if patients requested no trainee participation. CONCLUSIONS: There is a wide variety in the current practice of disclosure and level of information given regarding trainee participation in surgery. This will influence patients' expectations, experiences, and satisfaction. PMID- 22302065 TI - Systemic immunoglobulin G4 (IgG4) disease and idiopathic orbital inflammation; removing 'idiopathic' from the nomenclature? AB - The discovery of systemic disease related to raised tissue and serum immunoglobulin G4 (IgG4) is changing diagnostic and therapeutic practice in many medical specialties. Orbital inflammation remains a diverse and heterogeneous group of disorders that can pose a diagnostic and therapeutic challenge, but with improved understanding and corresponding diagnostic advances the previously expansive group of idiopathies is reducing. The recent discovery that IgG4 has a causative role in a subtype of, what is currently termed, idiopathic orbital inflammation is encouraging. The term 'idiopathic' can now be removed from the nomenclature for another subtype of orbital inflammation. IgG4 disease should be especially considered in patients with a bilateral dacryoadenitis and systemic features (eg, lung and gastrointestinal involvement). However, reports are emerging suggesting that IgG4 may be responsible for more diverse disease subtypes. The relationship between IgG4-related disease and lymphoma remains unknown but vigilance is required. PMID- 22302066 TI - Interferon-gamma release assay as a diagnostic test for tuberculosis-associated uveitis. AB - BACKGROUND: To study the use of interferon-gamma release assay (IFN-gamma) (IGRAs) as a diagnostic test for tuberculosis (TB)-associated uveitis (TAU). DESIGN: Prospective cohort study. PARTICIPANTS: Consecutive new patients (n=162) with clinical ocular signs suggestive of TAU, seen >1 year period at a single tertiary center. METHODS: All subjects underwent investigations to rule out underlying disease, including T-SPOT.TB and tuberculin skin test (TST). Twenty one subjects with underlying disease and three with interdeterminate T-SPOT.TB results were excluded. Those with T-SPOT.TB- or TST-positive results were referred to infectious diseases physician for evaluation. Anti-TB therapy (ATT) was prescribed if required. Patients' treatment response and recurrence were monitored for six months after completion of ATT, if given; or 1 year if no ATT was given. MAIN OUTCOME MEASURE: Diagnosis of TAU. RESULTS: Mean age of study cohort (n=138) was 46.8 +/- 15.3 years. Majority were Chinese (n=80, 58.0%) and female (n=75, 54.3%). TST was more sensitive than T-SPOT.TB (72.0% vs 36.0%); but T-SPOT.TB was more specific (75.0% vs 51.1%) for diagnosing TAU. Patients with either a T-SPOT.TB (1.44; 95% confidence intervals (CI), 0.86-2.42) or TST (1.47; 95% CI, 1.12-1.94)-positive result are more likely to have TAU. The accuracy of diagnosing TAU increases when both tests are used in combination (area under the receiver operator curve=0.665; 95% CI, 0.533-0.795). Patients with both tests positive are 2.16 (95% CI, 1.23-3.80) times more likely to have TAU. Negative T SPOT.TB or TST results do not exclude TAU (negative likelihood ratios <1.0). CONCLUSIONS: We recommend using a combination of clinical signs, IGRA, and TST to diagnose TAU. PMID- 22302067 TI - To assess the results of the clinical outcome of high volume cataract operations performed by a fellow and a consultant in Moorfields Eye Hospital. PMID- 22302068 TI - Predictors of perceived empathy among patients visiting primary health-care centers in central Ethiopia. AB - BACKGROUND: Empathy is crucial to the achievement of patient centeredness consultations. However, it has not been frequently studied particularly in resource-limited settings. OBJECTIVE: To identify predictors of patient reports indicating greater empathy among providers during patient visit to primary health care facilities. PARTICIPANTS: A cross-sectional study was conducted to assess the level of satisfaction among 768 out-patients, who consecutively visited six health centers in central Ethiopia. Patients were recruited from health centers under study based on proportional to size allocation. Multiple linear regression was used to assess the relationship between empathy scores and other patient factors. RESULTS: The mean perceived empathy score was 31.34 +/- 8.37 (range of possible values: 10-50). Patient-related factors that were negatively associated with perceived empathy were Tigre and Guraghe ethnicity [beta = -4.45; 95% confidence interval (CI) = -6.86 to -2.03], Wakefena religion (beta = -2.09; 95% CI = -3.82 to -0.35), lack of privacy during consultation (beta = -1.62; 95% CI = -2.57 to -0.68), involvement of family in consultation (beta = -1.45; 95% CI = 2.17 to -0.12) and not revealing one's own private issues (beta = -1.25; 95% CI = -2.17 to -0.33). Positive associations with provider empathy scores were found for those who reported knowing their provider (beta = 2.42; 95 CI = 1.70 to 4.13), non-verbal communication (beta = 0.88; 95% CI = 0.80 to 0.96) and perceived technical competency (beta = 0.12; 95% CI = 0.05 to 0.19). CONCLUSIONS: Perceived empathy in this study was lower than the findings reported in earlier studies. Health-care providers committed to the delivery of patient-centered care should take note of the determinants of better empathy as perceived by their clients. PMID- 22302069 TI - Quality improvement of nurse-led aftercare to outpatients with coronary heart disease: report of a case study. AB - QUALITY ISSUE: Improving preventive care for patients with coronary disease can be difficult to implement effectively with available resources. Assessing the implementation of a new improvement program can also be challenging when resources are constrained. INITIAL ASSESSMENT: In 2006, a nurse-led outpatient clinic was introduced in the hospital. CHOICE OF SOLUTION: The use of quality indicators (QIs), interviews and regular meetings to enable ongoing assessment of the success of implementation. IMPLEMENTATION: Quality improvement was promoted by providing regular reports on QIs to the CARDIOCARE Steering and Working group. Interviews with stakeholders were held, medical records were investigated and minutes of meetings were analyzed. The main change in CARDIOCARE concerned the targeted patient group. EVALUATION: CARDIOCARE performed well in meeting requirements of quality such as clinical effectiveness. There is, however, still room for improvement and some new QIs should be considered by stakeholders; for example, better registration of risk factors is needed. LESSONS LEARNED: An initial period of time is necessary to examine whether QIs stated in the care protocol are realistic in clinical practice and whether it is feasible to collect data about these criteria. Stakeholders should communicate about these indicators on a regular basis. A Plan-Do-Check-Act cycle is needed in order to improve care processes and performance. In addition, systematic administration of data about indicators is required. For nurse-led outpatient secondary prevention, it is advisable to appoint a single nurse as a case manager who is responsible for checking the registration of QIs and their evaluation. PMID- 22302070 TI - Patient Safety Friendly Hospital Initiative: from evidence to action in seven developing country hospitals. AB - QUALITY PROBLEM: Recent evidence in the level of patient safety from hospitals in six developing countries in the Eastern Mediterranean Region has demonstrated the high prevalence of adverse events, the excessive rate of death and permanent disability and their high preventability. The Patient Safety Friendly Hospital Initiative (PSFHI) has been launched to respond to these challenges. INITIAL ASSESSMENT: The principal approach of the PSFHI has been to develop an assessment manual that has 140 patient safety standards across five domains--leadership and management, patients and public involvement, safe evidence-based clinical practices, safe environment and lifelong learning. CHOICE OF SOLUTION AND IMPLEMENTATION: Ministries of health of seven countries--Egypt, Jordan, Morocco, Pakistan, Sudan, Tunisia and Yemen were asked to nominate one hospital for assessment and then follow-up with an improvement plan. EVALUATION: The standards are divided into critical (20), core (90) and developmental (30). The range of critical standards, the compulsory standards with which a hospital has to comply, achieved by participating hospitals was 8-78%. Overall, in the domain of leadership and management the highest compliance was 47%, for patients and public involvement 25%, for safe evidence-based clinical practice 53%, for safe environment 64% and for lifelong learning 27%. LESSONS LEARNED: This is the first systematic multi-country initiative in the Eastern Mediterranean Region, which provides compelling evidence that assessment of patient safety standards is feasible and applicable in resource-poor settings and there are significant opportunities for improving the level of patient safety in these hospitals. PMID- 22302071 TI - Disease-management partnership functioning, synergy and effectiveness in delivering chronic-illness care. AB - OBJECTIVE: This study explored associations among disease-management partnership functioning, synergy and effectiveness in the delivery of chronic-illness care. DESIGN: This study had a cross-sectional design. SETTING AND PARTICIPANTS: The study sample consists of 218 professionals (out of 393) participating in 22 disease-management partnerships in various regions of the Netherlands. MAIN OUTCOME MEASURES: We assessed the relationships among partnership functioning, synergy and effectiveness in the delivery of chronic-illness care. Partnership functioning was assessed through leadership, resources, administration and efficiency. Synergy was considered the proximal outcome of partnership functioning, which, in turn, influenced the effectiveness of disease-management partnerships [measured with the Assessment of Chronic Illness Care (ACIC) survey instrument]. RESULTS: Overall ACIC scores ranged from 3 to 10, indicating basic/intermediate to optimal/comprehensive delivery of chronic-illness care. The results of the regression analysis demonstrate that partnership effectiveness was positively associated with leadership (beta = 0.25; P<= 0.01), and resources (beta = 0.31; P<= 0.001). No significant relationship was found between administration, efficiency and partnership effectiveness. Partnership synergy acted as a mediator for partnership functioning and was statistically significantly associated with partnership effectiveness (beta = 0.25; P<= 0.001). CONCLUSION: Disease-management partnerships seemed better able to deliver higher levels of chronic-illness care when synergy is created between partners. Synergy was more likely to emerge with boundary-spanning leaders who understood and appreciated partners' different perspectives, could bridge their diverse cultures and were comfortable sharing ideas, resources and power. In addition, the acknowledgement of and ability to use members' resources are valuable in engaging partners' involvement and achieving synergy in disease-management partnerships. PMID- 22302072 TI - Uveal melanoma: the inflammatory microenvironment. AB - Uveal melanoma is a highly malignant intraocular tumor with quite homogeneous tumor tissue and a diffuse leukocytic infiltration. In contrast with many other malignancies, the presence of infiltrating macrophages and T cells is associated with a poor prognosis rather than a good one. The clear link between inflammation and cancer in this malignancy provides a paradigm for macrophage plasticity and function. Macrophages in uveal melanoma have an M2-like phenotype and are associated with the loss of one specific chromosome - monosomy 3. The central players involved in this process and discussed in this review include macrophages, T lymphocytes, chemokines and cytokines, including the macrophage attraction molecules. When a tumor acquires the ability to release significant amounts of macrophage-attraction molecules it causes the expansion of a population of myeloid immature cells that may not only help the tumor to suppress immune reactions but also aid in the construction of new blood vessels for tumor growth. A better understanding of the molecular basis of a local myelomonocytic cell population will bring a better understanding of the immunopathology of this disease and will lead to therapeutic interventions in uveal melanoma. This review focuses on the roles of the local inflammatory microenvironment in the development and progression of uveal melanoma. PMID- 22302073 TI - Dehydrogenative Heck coupling of biologically relevant N-heteroarenes with alkenes: discovery of fluorescent core frameworks. AB - A Pd/Cu-catalyzed dehydrogenative Heck coupling is established that allows direct alkenylation of various biologically relevant N-heteroarenes with alkenes. The resulting pi-extended alkenylated N-heteroarenes exhibit interesting fluorescent properties and have proven to be potentially useful fluorescent probes for bioimaging. PMID- 22302074 TI - Marginal structural models for case-cohort study designs to estimate the association of antiretroviral therapy initiation with incident AIDS or death. AB - To estimate the association of antiretroviral therapy initiation with incident acquired immunodeficiency syndrome (AIDS) or death while accounting for time varying confounding in a cost-efficient manner, the authors combined a case cohort study design with inverse probability-weighted estimation of a marginal structural Cox proportional hazards model. A total of 950 adults who were positive for human immunodeficiency virus type 1 were followed in 2 US cohort studies between 1995 and 2007. In the full cohort, 211 AIDS cases or deaths occurred during 4,456 person-years. In an illustrative 20% random subcohort of 190 participants, 41 AIDS cases or deaths occurred during 861 person-years. Accounting for measured confounders and determinants of dropout by inverse probability weighting, the full cohort hazard ratio was 0.41 (95% confidence interval: 0.26, 0.65) and the case-cohort hazard ratio was 0.47 (95% confidence interval: 0.26, 0.83). Standard multivariable-adjusted hazard ratios were closer to the null, regardless of study design. The precision lost with the case-cohort design was modest given the cost savings. Results from Monte Carlo simulations demonstrated that the proposed approach yields approximately unbiased estimates of the hazard ratio with appropriate confidence interval coverage. Marginal structural model analysis of case-cohort study designs provides a cost-efficient design coupled with an accurate analytic method for research settings in which there is time-varying confounding. PMID- 22302075 TI - Physical activity, sedentary behavior, and leukocyte telomere length in women. AB - Leukocyte telomere length (LTL) is a potential indicator of cellular aging; however, its relation to physical activity and sedentary behavior is unclear. The authors examined cross-sectionally associations among activity, sedentary behavior, and LTL among 7,813 women aged 43-70 years in the Nurses' Health Study. Participants self-reported activity by questionnaire in 1988 and 1992 and sedentary behavior in 1992. Telomere length in peripheral blood leukocytes, collected in 1989-1990, was measured by quantitative polymerase chain reaction. The least-squares mean telomere length (z-score) was calculated after adjustment for age and other potential confounders. For total activity, moderately or highly active women had a 0.07-standard deviation (SD) increase in LTL (2-sided P(trend) = 0.02) compared with those least active. Greater moderate- or vigorous-intensity activity was also associated with increased LTL (SD = 0.11 for 2-4 vs. <1 hour/week and 0.04 for >=7 vs. <1 hour/week; 2-sided P(trend) = 0.02). Specifically, calisthenics or aerobics was associated with increased LTL (SD = 0.10 for >=2.5 vs. 0 hours/week; 2-sided P(trend) = 0.04). Associations remained after adjustment for body mass index. Other specific activities and sitting were unassociated with LTL. Although associations were modest, these findings suggest that even moderate amounts of activity may be associated with longer telomeres, warranting further investigation in large prospective studies. PMID- 22302076 TI - Evaluation of moderate alcohol use and cognitive function among men using a Mendelian randomization design in the Guangzhou biobank cohort study. AB - Observational studies usually show that moderate alcohol use is associated with better cognitive function. Such studies are vulnerable to residual confounding arising from systematic differences between moderate alcohol users and others. A Mendelian randomization study carried out in a suitable population, such as southern Chinese men, in which alcohol use is low to moderate and is influenced by genotype, offers an alternative and superior approach for clarifying the causal effect of moderate alcohol use on cognitive function. The authors used aldehyde dehydrogenase 2 (ALDH2) genotype (AA, GA, or GG) as an instrumental variable in 2-stage least squares analysis to obtain unbiased estimates of the relation of alcohol consumption (measured in alcohol units (10 g ethanol) per day) with cognitive function, assessed from delayed 10-word recall score (n = 4,707) and Mini-Mental State Examination (MMSE) score (n = 2,284), among men from the Guangzhou Biobank Cohort Study (2003-2008). ALHD2 genotype was strongly associated with alcohol consumption, with an F statistic of 71.0 in 2-stage least squares analysis. Alcohol consumption was not associated with delayed 10-word recall score (-0.03 words per alcohol unit, 95% confidence interval: -0.18, 0.13) or MMSE score (0.06 points per alcohol unit, 95% confidence interval: -0.22, 0.34). Moderate alcohol use is unlikely to be cognitively protective. PMID- 22302077 TI - Bio-inspired variable structural color materials. AB - Natural structural color materials, especially those that can undergo reversible changes, are attracting increasing interest in a wide variety of research fields. Inspired by the natural creatures, many elaborately nanostructured photonic materials with variable structural colors were developed. These materials have found important applications in switches, display devices, sensors, and so on. In this critical review, we will provide up-to-date research concerning the natural and bio-inspired photonic materials with variable structural colors. After introducing the variable structural colors in natural creatures, we will focus on the studies of artificial variable structural color photonic materials, including their bio-inspired designs, fabrications and applications. The prospects for the future development of these fantastic variable structural color materials will also be presented. We believe this review will promote the communications among biology, bionics, chemistry, optical physics, and material science (196 references). PMID- 22302078 TI - The effect of the ATG16L1 Thr300Ala polymorphism on susceptibility and outcome of patients with epithelial cell-derived thyroid carcinoma. PMID- 22302079 TI - Utility of preoperative examination and magnetic resonance imaging for diagnosis of anterior vaginal wall masses. AB - INTRODUCTION AND HYPOTHESIS: The clinical evaluation of anterior vaginal wall masses can present a dilemma, as there are no well-defined pathways for diagnosis and management. Our objective was to evaluate the role and accuracy of preoperative exam and magnetic resonance imaging (MRI) for these masses. METHODS: We identified women with a mass using billing codes for 10 years. We compared data from the preoperative evaluation to postoperative pathology if available. RESULTS: Analysis after chart review on 47 women was performed. Of the 34 women who had surgery, 28 (82.4%) also underwent an MRI. MRI diagnosis was accurate in 22/28 women compared to histology, inconclusive in 4, and inaccurate in 2. Preoperative diagnosis, including exam, MRI, and cystourethroscopy, had a diagnostic accuracy of 94.1% compared to postoperative diagnosis. The positive predictive value of MRI alone was 91.7%. CONCLUSIONS: Preoperative diagnosis using exam, MRI, and cystourethroscopy have a high diagnostic accuracy for anterior vaginal wall masses. PMID- 22302080 TI - Propofol-induced coved-type electrocardiogram during catheter ablation of paroxysmal atrial fibrillation. A case of Brugada syndrome? AB - We report a case of a young man with paroxysmal atrial fibrillation, in whom a characteristic coved-type Brugada pattern developed during catheter ablation performed under sedation with propofol. After immediate discontinuation of the propofol infusion, coved-type ST-segment elevation gradually resolved and no ventricular arrhythmias occurred. An ajmaline challenge failed to unmask a coved type electrocardiogram and genetic testing was negative for ion channel mutations related to Brugada syndrome. PMID- 22302081 TI - Polysomnography underestimates altered cardiac autonomic control in patients with obstructive sleep apnea. AB - BACKGROUND: Repetitive nocturnal sympathetic activation during episodes of apnea and postapneic hyperventilation increases cardiovascular risk. The effects of hypopnea and non-apneic, non-hypopneic intervals before and after hypopnea/apnea on sympathico-vagal balance have not been assessed yet. HYPOTHESIS: Hypopnea and non-apneic, non-hypopneic intervals before and after hypopnea/apnea cause increased sympathetic activity when compared to normal respiration in nonREM stages 2-4. METHODS: A total of 34 patients were studied using in-laboratory polysomnography including continuous ECG recording. Absolute spectral power of heart rate variability in the very low (VLF), low (LF), and high frequency (HF) bands and low frequency to high frequency power ratio (LF/HF ratio) were analyzed during apnea, hypopnea, and during the pre- and post-phases of such respiratory episodes and compared to spectral powers during normal respiration in nonREM sleep 2-4. RESULTS: Patients with hypopnea and/or obstructive apnea showed higher power of VLF and the LF/HF ratio in intervals of hypopnea/apnea and in non apneic, non-hypopneic intervals before and after hypopnea/apnea compared to normal respiration in nonREM stages 2-4. CONCLUSION: The effect of sleep disordered breathing on alteration of autonomic tone in patients with hypopnea and obstructive apnea is more severe than estimated by conventional polysomnographic assessment of apnea and hypopnea. Patients with sleep apnea show a sympathetic overdrive not only during phases of hypopnea and obstructive apnea but also in non-apnea, non-hypopnea intervals before and after hypopnea, and obstructive apnea. PMID- 22302083 TI - Depression, fatigue, and health-related quality of life in head and neck cancer patients: a prospective pilot study. AB - PURPOSE: To assess the prevalence of depression and fatigue symptoms in head and neck cancer patients during radiotherapy treatment and relate them symptoms with these patients' quality of life. METHOD: This is a prospective study. The Beck Depression Inventory (BDI), Piper Fatigue Scale-revised and Functional Assessment Cancer Therapy Head and Neck (FACT-H&N) were applied to 41 head and neck cancer patients at three times: at the start of treatment (T1), approximately 15 days after the start of treatment (T2) and at the end of treatment (T3), approximately 30 days after the start of the radiotherapy. RESULTS: The mean BDI and PIPER increased during the radiotherapy treatment. BDI scores did not demonstrate the presence of depression, although the number of symptoms increased, and the presence of fatigue rose as treatment advanced. The mean FACT H&N decreased in the middle and at the end of treatment, indicating worsening in these patients' Quality of Life. CONCLUSIONS: Depression and fatigue symptoms increased during radiotherapy treatment, while QoL levels decreased. This demonstrates that these symptoms are strongly correlated and that their presence negatively influenced QoL. At the start of treatment, nurses need to advise patients and plan care, offering interventions to decrease these symptoms and improve QoL. PMID- 22302084 TI - In vitro activities of nisin alone or in combination with vancomycin and ciprofloxacin against methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains. AB - BACKGROUND: We investigated the in vitro activities of nisin alone or in combination with vancomycin and ciprofloxacin against methicillin-resistant (MRSA) and -susceptible Staphylococcus aureus (MSSA) strains. METHODS: The minimum inhibitory concentrations were determined by microbroth dilution technique. Antibiotic combinations were assessed using the checkerboard technique. The time-kill curve method was used for determining the bactericidal activity of nisin alone and in combination. RESULTS: For both MSSA and MRSA strains, the minimum inhibitory concentrations of nisin ranged between 4 and 16 mg/l. With a fractional inhibitory concentration of >=0.5 as borderline, synergistic interactions were seen in three of five isolates with nisin ciprofloxacin compared to two of five isolates with nisin-vancomycin combinations against both MSSA and MRSA. No antagonism was observed. The results of time-kill curve analysis demonstrated concentration-dependent rapid bactericidal activity of nisin and synergism almost in all strains when nisin was used in combination with ciprofloxacin, and early synergistic interactions in some of the strains when it was used in combination with vancomycin. CONCLUSION: Nisin seems to be a good candidate for further investigations in the treatment of Gram-positive bacteria, alone or in combination with antibiotics. PMID- 22302082 TI - Patient-reported outcome instruments used to assess pain and functioning in studies of bisphosphonate treatment for bone metastases. AB - PURPOSE: When treating metastatic bone disease, relief of bone pain is often a key outcome. Because pain cannot be quantified with objective clinical measures, patient-reported outcome (PRO) measures are required to assess patients' subjective experience. The goal of the current review was to examine measures used to assess pain, as well as the impact of pain on functional status and health-related quality of life (HRQL), in trials of bisphosphonates for the treatment of bone metastases. METHODS: A literature search focused on articles published from January 1999 to April 2009. RESULTS: A total of 49 articles were located that used PROs to assess pain-related outcomes of bisphosphonate treatment for bone metastases. The Brief Pain Inventory was the most commonly used multi-item instrument. However, the most common approach for assessing pain was to administer a single-item scale such as a visual analog scale, numerical rating scale, or verbal rating scale. Of the 49 studies, 19 included a PRO assessing functional status or HRQL. CONCLUSIONS: Although pain is an important outcome of trials examining treatment for bone metastases, the current review suggests that there is little consistency in PRO measurement across studies. Furthermore, presentation of measures often lacked clear description, information on measurement properties, citations, clarity regarding method of administration, and consistent instrument names. Recommendations are provided for instrument validation within the target population, assessment of content validity, use of PRO instruments recently developed for patients with bone metastases, clear description of instruments, and implementation of measures consistent with recommendations from instrument developers. PMID- 22302085 TI - Relationship between kidney damage and stroke types in Japanese patients. AB - BACKGROUND: Kidney disease is a known risk factor for stroke. This study investigated the relationship between kidney damage and stroke types. METHODS: A total of 525 incident stroke patients were registered and followed for 1 year. The prevalence of kidney damage [proteinuria and/or renal insufficiency (estimated glomerular filtration rate<60 ml/min/1.73 m(2))] in incident stroke and its effects on 1-year prognosis were examined. RESULTS: Among all stroke patients, kidney damage and its component (proteinuria and renal insufficiency) were commonly observed (48.2, 25.5, and 33.9%, respectively). The prevalence of ischemic stroke was significantly higher in patients with kidney damage (75.9%) than in those without (58.9%). The most frequent type of stroke among all patients with kidney damage and renal insufficiency only was cardioembolic infarction. In contrast, in patients with proteinuria only and patients without kidney damage, the most frequent type was subcortical and subarachnoid hemorrhage, respectively. Multiple logistic regression analysis showed that kidney damage or the combination of its components were independently associated with 1-year death [odds ratio (OR) 3.04, 95% confidence interval (CI) 1.40-6.59, P = 0.005 for kidney damage, OR 2.82, 95% CI 1.05-7.58, P = 0.040 for proteinuria only, and OR 5.77, 95% CI 2.23-15.0, P<0.001 for both proteinuria and renal insufficiency]. In addition, for 1-year outcomes, there were selective associations between ischemic stroke and proteinuria and between hemorrhagic stroke and renal insufficiency. CONCLUSIONS: This study shows that kidney damage is common in Japanese stroke patients, and proteinuria and renal insufficiency are differentially related to development and prognosis, depending stroke types. PMID- 22302086 TI - An explorative analysis of secretory receptor for advanced glycation endproducts in primary focal segmental glomerulosclerosis. AB - BACKGROUND: Despite remarkable medical progress, the main pathogenetic mechanisms of focal segmental glomerulosclerosis (FSGS) have not been fully delineated and its prognosis is poor at present. Recently, it was revealed that the receptor for advanced glycation endproducts (RAGE) was highly expressed at the base of podocytes with an up-regulation mainly in diabetic nephropathy. However, there is no report about the association between glomerulonephritis and RAGE. The aims of the current study were to explore the relationships between several clinical parameters and circulating soluble RAGE in primary FSGS and compare serum levels in primary FSGS with immunoglobulin A nephropathy (IgAN) and controls. METHODS: A total of 35 subjects aged >18 years were enrolled. Thirty-five subjects consisted of three groups: primary FSGS (N = 15), IgAN (N = 10), and normal controls (N = 10). Laboratory measurements of serum carboxymethyl-lysin (CML), soluble RAGE (sRAGE), and endogenous secretory RAGE (esRAGE) were performed. RESULTS: Serum esRAGE level in the FSGS group was higher than that in the IgAN group (0.55 +/- 0.32 ng/mL vs. 0.27 +/- 0.11 ng/mL, p = 0.013). There was no statistical difference between sRAGE and CML among the three groups. Within the FSGS group, esRAGE, but not sRAGE, was positively correlated with 24-h urinary protein (r = 0.553, p = 0.033) and negatively correlated with body mass index (r = -0.623, p = 0.013). In stepwise multiple regression analysis, body mass index and 24-h urinary protein were significant contributors to esRAGE within the FSGS group. CONCLUSION: This study showed that only the serum level of esRAGE, not sRAGE, was higher in the FSGS group than in the IgAN and control groups. The amount of 24-h proteinuria was also related to the serum level of esRAGE in the FSGS group. PMID- 22302087 TI - Low birth weight and end-stage renal disease: demographic analysis by region in Japan. AB - BACKGROUND We have previously shown regional differences in the incidence of end stage renal disease (ESRD)within Japan, which is ethnically homogenous, suggesting that non-genetic factors may contribute to the differences.We examined regional distribution in the incidence of low birth weight (LBW), a surrogate for low nephron number,in our search for an explanation. METHODS: Each year, the Ministry of Health, Labour and Welfare of Japan and the Japanese Society for Dialysis Therapy report the number of LBW babies and patients initiating maintenance dialysis in each prefecture of Japan,respectively. In this study, we calculated the annual incidences of LBW and ESRD in 11 regions of Japan over a 24 year period from 1984 to 2007. RESULTS: There were distinct regional differences in the annual incidences of both LBW and ESRD (p<0.0001).These regional distributions persisted despite consistent increases (p<0.0001) in incidences of both LBW and ESRD during the study period. Compared with the reference group consisting of 3 regions with the lowest LBW incidence, the odds ratios for ESRD (95% confidence interval) of the 5 regions with intermediate LBW incidence and the 3 regions with the highest LBW incidence are 1.09(1.05-1.14) and 1.29 (1.22 1.35), respectively. The annual incidence of LBW was positively correlated with annual incidence of ESRD in their regional distribution across 11 regions (r = 0.66, p = 0.03). CONCLUSIONS: The present study, relating regional distribution between LBW and ESRD dynamics in a nationwide population of Japan, revealed that the marked regional differences in the incidence of ESRD within Japan could be explained by a similar regional distribution in the incidence of LBW. PMID- 22302088 TI - A selective fluorescent turn-on NIR probe for cysteine. AB - A selective and sensitive turn-on fluorescent NIR probe for cysteine has been developed. Cleavage of 2,4-dinitrobenzenesulfonyl (DNBS) with thiols switches the weakly fluorescent aza-BODIPY dye (lambda(em) = 734 nm, Phi(f) = 0.03) to a strongly fluorescent species in the NIR region (lambda(em) = 755 nm, Phi(f) = 0.14). PMID- 22302089 TI - Imaging small human prostate cancer xenografts after pretargeting with bispecific bombesin-antibody complexes and targeting with high specific radioactivity labeled polymer-drug conjugates. AB - PURPOSE: Pretargeting with bispecific monoclonal antibodies (bsMAb) for tumor imaging was developed to enhance target to background activity ratios. Visualization of tumors was achieved by the delivery of mono- and divalent radiolabeled haptens. To improve the ability to image tumors with bsMAb, we have combined the pretargeting approach with targeting of high specific activity radiotracer labeled negatively charged polymers. The tumor antigen-specific antibody was replaced with bombesin (Bom), a ligand that binds specifically to the growth receptors that are overexpressed by many tumors including prostate cancer. Bomanti- diethylenetriaminepentaacetic acid (DTPA) bispecific antibody complexes were used to demonstrate pretargeting and imaging of very small human prostate cancer xenografts targeted with high specific activity 111In- or 99mTc labeled negatively charged polymers. METHODS: Bispecific antibody complexes consisting of intact anti-DTPA antibody or Fab' linked to Bom via thioether bonds (Bom-bsCx or Bom-bsFCx, respectively) were used to pretarget PC-3 human prostate cancer xenografts in SCID mice. Negative control mice were pretargeted with Bom or anti-DTPA Ab. 111In-Labeled DTPA-succinyl polylysine (DSPL) was injected intravenously at 24 h (7.03 +/- 1.74 or 6.88 +/- 1.89 MBq 111In-DSPL) after Bom bsCx or 50 +/- 5.34 MBq of 99mTc-DSPL after Bom-bsFCx pretargeting, respectively. Planar or single photon emission computed tomography (SPECT)/CT gamma images were obtained for up to 3 h and only planar images at 24 h. After imaging, all mice were killed and biodistribution of 111In or 99mTc activities were determined by scintillation counting. RESULTS: Both planar and SPECT/CT imaging enabled detection of PC-3 prostate cancer lesions less than 1-2 mm in diameter in 1-3 h post 111In-DSPL injection. No lesions were visualized in Bom or anti-DTPA Ab pretargeted controls. 111In-DSPL activity in Bom-bsCx pretargeted tumors (1.21 +/ 0.36 %ID/g) was 5.4 times that in tumors pretargeted with Bom or anti-DTPA alone (0.22 +/- 0.08, p = 0.001). PC-3 xenografts pretargeted with Bom-bsFCx and targeted with 99mTc-DSPL were visualizable by 1-3 h. Exquisite tumor uptake at 24 h (6.54 +/- 1.58 %ID/g) was about 15 times greater than that of Bom pretargeted controls (0.44 +/- 0.17, p = 0.002). CONCLUSION: Pretargeting prostate cancer with Bom-bsCx or Bom-bsFCx enabled fast delivery of high specific radioactivity 111In- or 99mTc-labeled polymer-drug conjugates resulting in visualization of lesions smaller than 1- 2 mm in diameter within 3 h. PMID- 22302090 TI - Biodistribution and dosimetry of 123I-mZIENT: a novel ligand for imaging serotonin transporters. AB - PURPOSE: 123I-labelled mZIENT (2beta-carbomethoxy-3beta-(3'-((Z)-2 iodoethenyl)phenyl)nortropane) has been developed as a radioligand for the serotonin transporter. The aim of this preliminary study was to assess its whole body biodistribution in humans and estimate dosimetry. METHODS: Three healthy controls and three patients receiving selective serotonin reuptake inhibitor (SSRI) therapy for depression were included (two men, four women, age range 41-56 years). Whole-body imaging, brain SPECT imaging and blood and urine sampling were performed. Whole-body images were analysed using regions of interest (ROIs), time activity curves were derived using compartmental analysis and dosimetry estimated using OLINDA software. Brain ROI analysis was performed to obtain specific-to nonspecific binding ratios in the midbrain, thalamus and striatum. RESULTS: Initial high uptake in the lungs decreased in later images. Lower uptake was seen in the brain, liver and intestines. Excretion was primarily through the urinary system. The effective dose was estimated to be of the order of 0.03 mSv/MBq. The organ receiving the highest absorbed dose was the lower large intestine wall. Uptake in the brain was consistent with the known SERT distribution with higher specific-to-nonspecific binding in the midbrain, thalamus and striatum in healthy controls compared with patients receiving SSRI therapy. CONCLUSION: 123I-mZIENT may be a promising radioligand for imaging the serotonin transporters in humans with acceptable dosimetry. PMID- 22302091 TI - Correction of an important typographical error in the European Association of Nuclear Medicine (EANM) guidelines. PMID- 22302092 TI - Measuring glomerular filtration rate from plasma clearance of 51Cr-EDTA: quality assurance. PMID- 22302094 TI - Action on AMD. Optimising patient management: act now to ensure current and continual delivery of best possible patient care. AB - In recent years, there have been significant advances in the clinical management of patients with wet age-related macular degeneration (wet AMD)--a rapidly progressing and potentially blinding degenerative eye disease. Wet AMD is responsible for more than half of registered severe sight impairment (blindness) in the United Kingdom, and patients who are being treated for wet AMD require frequent and long-term follow-up for treatment to be most effective. The clinical workload associated with the frequent follow-up required is substantial. Furthermore, as more new patients are diagnosed and the population continues to age, the patient population will continue to increase. It is thus vital that clinical services continue to adapt so that they can provide a fast and efficient service for patients with wet AMD. This Action on AMD document has been developed by eye health-care professionals and patient representatives, the Action on AMD group. It is intended to highlight the urgent and continuing need for change within wet AMD services. This document also serves as a guide for eye health-care professionals, NHS commissioners, and providers to present possible solutions for improving NHS retinal and macular services. Examples of good practice and service development are considered and can be drawn upon to help services meet the recommended quality of care and achieve best possible outcomes. PMID- 22302095 TI - Antihypertensive and cardiorenal protective effects of SM-368229, a novel mineralocorticoid receptor antagonist, in aldosterone/salt-treated rats. AB - The purpose of this study was to evaluate the effects of SM-368229, a novel mineralocorticoid receptor (MR) antagonist, on the blood pressure and cardiorenal injury markers in aldosterone/salt-treated hypertensive rats, in comparison to those of spironolactone (SPI). Uninephrectomized rats, given 1% NaCl to drink, were infused with aldosterone (0.75 MUg/h, s.c.). In experiment 1, SM-368229 (10, 30 mg/kg) or SPI (100 mg/kg) were administered for 14 days immediately after aldosterone/salt loading. In experiment 2, SM-368229 (10 mg/kg) or SPI (100 mg/kg) were administered for 10 days after 10 days of aldosterone/salt loading. In both experiments, SM-368229 prevented the increase in systolic blood pressure, heart/kidney weights, and urinary protein/N-acetyl-beta-D- glucosaminidase excretion caused by aldosterone infusion. In real-time polymerase chain reaction analysis, SM-368229 abolished aldosterone-induced gene expression levels for inflammatory, fibrosis and oxidative stress markers in hearts and kidneys. The antihypertensive effect of SM-368229 (30 mg/kg) was superior to that of SPI, and the antihypertensive and cardiorenal protective effects of SM-368229 (10 mg/kg) were similar to those of SPI (100 mg/kg) in both experiments. These results clearly demonstrated that SM-368229 strongly attenuated the progression of hypertension and exerted cardiorenal protection in aldosterone/salt-treated hypertensive rats. PMID- 22302096 TI - The aurora kinase A inhibitor MLN8237 enhances cisplatin-induced cell death in esophageal adenocarcinoma cells. AB - Esophageal adenocarcinomas are poorly responsive to chemotherapeutics. This study aimed to determine the levels of Aurora kinase A (AURKA) and the therapeutic potential of MLN8237, an investigational AURKA inhibitor, alone and in combination with cisplatin. Using quantitative real-time PCR, we detected frequent AURKA gene amplification (15 of 34, 44%) and mRNA overexpression (37 of 44, 84%) in esophageal adenocarcinomas (P < 0.01). Immunohistochemical analysis showed overexpression of AURKA in more than two-thirds of esophageal adenocarcinoma tissue samples (92 of 132, 70%; P < 0.001). Using FLO-1, OE19, and OE33 esophageal adenocarinoma cell lines, with constitutive AURKA overexpression and mutant p53, we observed inhibition of colony formation with a single treatment of 0.5 MUmol/L MLN8237 (P < 0.05). This effect was further enhanced in combination with 2.5 MUmol/L cisplatin (P < 0.001). Twenty-four hours after treatment with the MLN8237 or MLN8237 and cisplatin, cell-cycle analyses showed a sharp increase in the percentage of polyploid cells (P < 0.001). This was followed by an increase in the percentage of cells in the sub-G(1) phase at 72 hours, concordant with the occurrence of cell death (P < 0.001). Western blot analysis showed higher induction of TAp73beta, PUMA, NOXA, cleaved caspase-3, and cleaved PARP with the combined treatment, as compared with a single-agent treatment. Using xenograft models, we showed an enhanced antitumor role for the MLN8237 and cisplatin combination, as compared with single-agent treatments (P < 0.001). In conclusion, this study shows frequent overexpression of AURKA and suggests that MLN8237 could be an effective antitumor agent, which can be combined with cisplatin for a better therapeutic outcome in esophageal adenocarcinomas. PMID- 22302097 TI - Cigarette smoke induces aberrant EGF receptor activation that mediates lung cancer development and resistance to tyrosine kinase inhibitors. AB - The EGF receptor (EGFR) and its downstream signaling are implicated in lung cancer development. Therefore, much effort was spent in developing specific tyrosine kinase inhibitors (TKI) that bind to the EGFR ATP-pocket, blocking EGFR phosphorylation/signaling. Clinical use of TKIs is effective in a subset of lung cancers with mutations in the EGFR kinase domain, rendering the receptor highly susceptible to TKIs. However, these benefits are limited, and emergence of additional EGFR mutations usually results in TKI resistance and disease progression. Previously, we showed one mechanism linking cigarette smoke to EGFR driven lung cancer. Specifically, exposure of lung epithelial cells to cigarette smoke-induced oxidative stress stimulates aberrant EGFR phosphorylation/activation with impaired receptor ubiquitination/degradation. The abnormal stabilization of the activated receptor leads to uncontrolled cell growth and tumorigenesis. Here, we describe for the first time a novel posttranslational mechanism of EGFR resistance to TKIs. Exposure of airway epithelial cells to cigarette smoke causes aberrant phosphorylation/activation of EGFR, resulting in a conformation that is different from that induced by the ligand EGF. Unlike EGF-activated EGFR, cigarette smoke-activated EGFR binds c-Src and caveolin-1 and does not undergo canonical dimerization. Importantly, the cigarette smoke-activated EGFR is not inhibited by TKIs (AG1478; erlotinib; gefitinib); in fact, the cigarette smoke exposure induces TKI-resistance even in the TKI-sensitive EGFR mutants. Our findings show that cigarette smoke exposure stimulates not only aberrant EGFR phosphorylation impairing receptor degradation, but also induces a different EGFR conformation and signaling that are resistant to TKIs. Together, these findings offer new insights into cigarette smoke-induced lung cancer development and TKI resistance. PMID- 22302098 TI - Navitoclax (ABT-263) reduces Bcl-x(L)-mediated chemoresistance in ovarian cancer models. AB - To examine the potential of combining Bcl-2 family inhibitors with chemotherapy in ovarian cancer, we evaluated a panel of 27 ovarian cancer cell lines for response to the combination of navitoclax (formerly ABT-263) and paclitaxel or gemcitabine. The majority of cell lines exhibited a greater than additive response to either combination, as determined by the Bliss independence model, and more than 50% of the ovarian cell lines exhibited strong synergy for the navitoclax/paclitaxel combination. To identify biomarkers for tumors likely to respond to this combination, we evaluated the protein levels of intrinsic apoptosis pathway components. Bcl-x(L) seems necessary, but not sufficient, for navitoclax/paclitaxel synergy in vitro, suggesting that exclusion of patients whose tumors have low or undetectable Bcl-x(L) would enrich for patients responsive to the combination. We evaluated Bcl-x(L) levels in ovarian cancer tumor tissue from 40 patients (20 taxane responsive and 20 with poor response to taxane) and found that patients with high Bcl-x(L) were less sensitive to taxane treatment (10 of 12) Bcl-x(L) positive patients, P = 0.014). These data support the use of navitoclax in combination with taxane-based therapy in ovarian cancer patients with high levels of Bcl-x(L). PMID- 22302099 TI - The thymidine phosphorylase inhibitor 5'-O-tritylinosine (KIN59) is an antiangiogenic multitarget fibroblast growth factor-2 antagonist. AB - 5'-O-Tritylinosine (KIN59) is an allosteric inhibitor of the angiogenic enzyme thymidine phosphorylase. Previous observations showed the capacity of KIN59 to abrogate thymidine phosphorylase-induced as well as developmental angiogenesis in the chicken chorioallantoic membrane (CAM) assay. Here, we show that KIN59 also inhibits the angiogenic response triggered by fibroblast growth factor-2 (FGF2) but not by VEGF in the CAM assay. Immunohistochemical and reverse transcriptase PCR analyses revealed that the expression of laminin, the major proteoglycan of the basement membrane of blood vessels, is downregulated by KIN59 administration in control as well as in thymidine phosphorylase- or FGF2-treated CAMs, but not in CAMs treated with VEGF. Also, KIN59 abrogated FGF2-induced endothelial cell proliferation, FGF receptor activation, and Akt signaling in vitro with no effect on VEGF-stimulated biologic responses. Accordingly, KIN59 inhibited the binding of FGF2 to FGF receptor-1 (FGFR1), thus preventing the formation of productive heparan sulphate proteoglycan/FGF2/FGFR1 ternary complexes, without affecting heparin interaction. In keeping with these observations, systemic administration of KIN59 inhibited the growth and neovascularization of subcutaneous tumors induced by FGF2-transformed endothelial cells injected in immunodeficient nude mice. Taken together, the data indicate that the thymidine phosphorylase inhibitor KIN59 is endowed with a significant FGF2 antagonist activity, thus representing a promising lead compound for the design of multitargeted antiangiogenic cancer drugs. PMID- 22302100 TI - Mimics of small ribozymes utilizing a supramolecular scaffold. AB - For elucidating the mechanism of the general acid/base catalysis of the hydrolysis of RNA phosphodiester bonds, a number of cleaving agents having two cyclen moieties tethered to a 1,3,5-triazine core have been prepared and their ability to bind and cleave uridylyl-3',5'-uridine (UpU) studied over a wide pH range. Around neutral pH, the cleaving agents form a highly stable ternary complex with UpU and Zn(II) through coordination of the uracil N3 and the cyclen nitrogen atoms to the Zn(II) ions. Under conditions where the triazine core exists in the deprotonated neutral form, hydrolysis of UpU, but not of adenylyl 3',5'-adenosine (ApA), is accelerated by approximately two orders of magnitude in the presence of the cleaving agents, suggesting general base rather than metal ion catalysis. The probable mechanism of the observed catalysis and implications to understanding the general acid/base-catalyzed phosphodiester hydrolysis by ribozymes are discussed. PMID- 22302101 TI - An essential role for p38 MAPK in cerebellar granule neuron precursor proliferation. AB - Development of the cerebellum occurs postnatally and is marked by a rapid proliferation of cerebellar granule neuron precursors (CGNPs). CGNPs are the cells of origin for SHH-driven medulloblastoma, the most common malignant brain tumor in children. Here, we investigated the role of ERK, JNK, and p38 mitogen activated protein kinases in CGNP proliferation. We found high levels of p38alpha in proliferating CGNPs. Concomitantly, members of the p38 pathway, such as ASK1, MKK3 and ATF-2, were also elevated. Inhibition of the Shh pathway or CGNP proliferation blunts p38alpha levels, irrespective of Shh treatment. Strikingly, p38alpha levels were high in vivo in the external granule layer of the postnatal cerebellum, Shh-dependent mouse medulloblastomas and human medulloblastomas of the SHH subtype. Finally, knocking down p38alpha by short hairpin RNA-carrying lentiviruses as well as the pharmacologically inhibiting of its kinase activity caused a marked decrease in CGNP proliferation, underscoring its requirement for Shh-dependent proliferation in CGNPs. The inhibition of p38alpha also caused a decrease in Gli1 and N-myc transcript levels, consistent with reduced proliferation. These findings suggest p38 inhibition as a potential way to increase the efficacy of treatments available for malignancies associated with deregulated SHH signaling, such as basal cell carcinoma and medulloblastoma. PMID- 22302102 TI - TDP-43 pathology in a case of hereditary spastic paraplegia with a NIPA1/SPG6 mutation. AB - Mutations in NIPA1 (non-imprinted in Prader-Willi/Angelman syndrome) have been described as a cause of autosomal dominant hereditary spastic paraplegia (HSP) known as SPG6 (spastic paraplegia-6). We present the first neuropathological description of a patient with a NIPA1 mutation, and clinical phenotype of complicated HSP with motor neuron disease-like syndrome and cognitive decline. Postmortem examination revealed degeneration of lateral corticospinal tracts and dorsal columns with motor neuron loss. TDP-43 immunostaining showed widespread spinal cord and cerebral skein-like and round neuronal cytoplasmic inclusions. We ruled out NIPA1 mutations in 419 additional cases of motor neuron disease. These findings suggest that hereditary spastic paraplegia due to NIPA1 mutations could represent a TDP-43 proteinopathy. PMID- 22302103 TI - Prevalence of vertebral fracture in oldest old nursing home residents. AB - We evaluated vertebral fracture prevalence using DXA-based vertebral fracture assessment and its influence on the Fracture Risk Assessment (FRAX) tool determined 10-year fracture probability in a cohort of oldest old nursing home residents. More than one third of the subjects had prevalent vertebral fracture and 50% osteoporosis. Probably in relation with the prevailing influence of age and medical history of fracture, adding these information into FRAX did not markedly modify fracture probability. INTRODUCTION: Oldest old nursing home residents are at very high risk of fracture. The prevalence of vertebral fracture in this specific population and its influence on fracture probability using the FRAX tool are not known. METHODS: Using a mobile DXA osteodensitometer, we studied the prevalence of vertebral fracture, as assessed by vertebral fracture assessment program, of osteoporosis and of sarcopenia in 151 nursing home residents. Ten-year fracture probability was calculated using appropriately calibrated FRAX tool. RESULTS: Vertebral fractures were detected in 36% of oldest old nursing home residents (mean age, 85.9 +/- 0.6 years). The prevalence of osteoporosis and sarcopenia was 52% and 22%, respectively. Ten-year fracture probability as assessed by FRAX tool was 27% and 15% for major fracture and hip fracture, respectively. Adding BMD or VFA values did not significantly modify it. CONCLUSION: In oldest old nursing home residents, osteoporosis and vertebral fracture were frequently detected. Ten-year fracture probability appeared to be mainly determined by age and clinical risk factors obtained by medical history, rather than by BMD or vertebral fracture. PMID- 22302105 TI - High prevalence of mutations in the EYS gene in Japanese patients with autosomal recessive retinitis pigmentosa. AB - PURPOSE: To screen for disease-causing mutations in the Eyes shut homolog (EYS) gene in Japanese patients with retinitis pigmentosa (RP). Methods. Blood samples were obtained from 68 RP patients and 68 controls. Genomic DNA was extracted from the blood samples and used for screening of mutations in the coding exons by direct sequencing. Each patient underwent a detailed clinical examination. RESULTS: Nine nucleotide sequence variations causing amino acid changes were observed in homozygous or heterozygous alleles in 26 patients but not in 68 controls. Seven truncating mutations were found in 21 (32.8%) of 64 patients with nonsyndromic RP composed of 23 autosomal recessive RP (arRP) and 41 sporadic cases. The most abundant mutation was p.S1653Kfs*2, which was generated by a single adenine insertion into exon 26 (c.4957dupA) and was carried by 15 patients. The mutation p.Y2935*, produced by a single nucleotide substitution (c.8805C>A) in the last exon, was carried by five patients. These two truncating mutations were probably founder mutations because each was carried by the particular haplotype. The patients with homozygous or compound heterozygous truncating mutations showed a severe decline in visual acuity, whereas those with a single truncating mutation showed a mild decline. CONCLUSIONS: One-third of Japanese patients with nonsyndromic arRP carried probable pathogenic mutations in the EYS gene, including two founder mutations. Because the genotype was correlated with the phenotype, genotyping in the EYS gene could be a valuable tool for predicting long-term prognoses of Japanese patients with arRP and thus could be useful for genetic counseling and future gene therapy. PMID- 22302104 TI - Osteocyte regulation of bone mineral: a little give and take. AB - Osteocytes actively participate in almost every phase of mineral handling by bone. They regulate the mineralisation of osteoid during bone formation, and they are also a major RANKL-producing cell. Osteocytes are thus able to liberate bone mineral by regulating osteoclast differentiation and activity in response to a range of stimuli, including bone matrix damage, bone disuse and mechanical unloading, oestrogen deficiency, high-dose glucocorticoid and chemotherapeutic agents. At least some of these activities may be regulated by the osteocyte secreted product, sclerostin. There is also mounting evidence that in addition to regulating phosphate homeostasis systemically, osteocytes contribute directly to calcium homeostasis in the mature skeleton. Osteocyte cell death and the local loss of control of bone mineralisation may be the cause of focal hypermineralisation of bone and osteopetrosis, as seen in aging and pathology. The sheer number of osteocytes in bone means that "a little give and take" in terms of regulation of bone mineral content translates into a powerful whole organism effect. PMID- 22302106 TI - Retrograde intubation during laryngeal cleft repair on cardiopulmonary bypass. AB - Retrograde intubation is part of the difficult airway algorithm in the American Society of Anesthesiologists, but its usage is rare in small pediatric patients with the advent of new intubation techniques. We present our experience of retrograde intubation for a 4-month-old patient who presented for laryngeal cleft repair on cardiopulmonary bypass. This case highlights the unique place for retrograde intubation in small patients in the current era. PMID- 22302107 TI - Apolipoprotein E e4 allele does not increase the risk of early postoperative delirium after major surgery. AB - BACKGROUND: A relationship between patients with a genetic predisposition to and those who develop postoperative delirium has not been yet determined. The aim of this study was to determine whether there is an association between apolipoprotein E epsilon 4 allele (APOE4) and delirium after major surgery. METHODS: Of 230 intensive care patients admitted to the post anesthesia care unit (PACU) over a period of 3 months, 173 were enrolled in the study. Patients' demographics and intra- and postoperative data were collected. Patients were followed for the development of delirium using the Intensive Care Delirium Screening Checklist, and DNA was obtained at PACU admission to determine apolipoprotein E genotype. RESULTS: Fifteen percent of patients developed delirium after surgery. Twenty-four patients had one copy of APOE4. The presence of APOE4 was not associated with an increased risk of early postoperative delirium (4% vs. 17%; P = 0.088). The presence of APOE4 was not associated with differences in any studied variables. Multivariate analysis identified age [odds ratio (OR) 9.3, 95% confidence interval (CI) 2.0-43.0, P = 0.004 for age >=65 years), congestive heart disease (OR 6.2, 95% CI 2.0-19.3, P = 0.002), and emergency surgery (OR 59.7, 95% CI 6.7-530.5, P < 0.001) as independent predictors for development of delirium. The Simplified Acute Physiology Score II (SAPS II) and The Acute Physiology and Chronic Health Evaluation II (APACHE II) were significantly higher in patients with delirium (P < 0.001 and 0.008, respectively). Hospital mortality rates of these patients was higher and they had a longer median PACU stay. CONCLUSIONS: Apolipoprotein e4 carrier status was not associated with an increased risk for early postoperative delirium. Age, congestive heart failure, and emergency surgery were independent risk factors for the development of delirium after major surgery. PMID- 22302108 TI - Radiation measurements around X-ray cabinet systems. AB - Security personnel who operate X-ray units for the control of hand luggage and personal items at airports are generally not under dosimetric surveillance. A significant increase in the number of inspected items per passenger, due to rigorous air traffic security measures, raises a question of extended exposure of these workers to scattered X-ray radiation. A new approach to investigating directions of breaches of scattered X-ray radiation in the area near to an X-ray cabinet system, which is based on using active electronic dosemeters is presented. Influence of the increase in the number of inspected items in time on the dose rate is described. Time-dependent dose rates have showed a very good correlation with passengers undergoing security control prior to boarding an airplane. Measurements confirmed that an increase in the dose rate, coinciding with rush hours, was caused by scattered radiation passing through incompletely closed lead curtains. It is found that the doses at the entrance to the inspection tunnel are 50% higher than those at the exit, which is a consequence of inherent operational characteristics of X-ray cabinet systems. PMID- 22302109 TI - CT/CT angiography and MRI findings predict recurrent stroke after transient ischemic attack and minor stroke: results of the prospective CATCH study. AB - BACKGROUND AND PURPOSE: Transient ischemic attack and minor stroke portend a substantial risk of recurrent stroke. MRI can identify patients at high risk for a recurrent stroke. However, MRI is not commonly available as an emergency. If similarly clinically predictive, a CT/CT angiographic (CTA) imaging strategy would be more widely applicable. METHODS: Five hundred ten patients with consecutive transient ischemic attack and minor stroke underwent CT/CTA and subsequent MRI. We assessed the risk of recurrent stroke within 90 days using standard clinical variables and predefined abnormalities on the CT/CTA (acute ischemia on CT and/or intracranial or extracranial occlusion or stenosis >=50%) and MRI (diffusion-weighted imaging-positive). RESULTS: There were 36 recurrent strokes (7.1%; 95% CI, 5.0-9.6). Median time to the event was 1 day (interquartile range, 7.5). Median time from onset to CTA was 5.5 hours (interquartile range, 6.4 hours) and to MRI was 17.5 hours (interquartile range, 12 hours). Symptoms ongoing at first assessment (hazard ratio, 2.2; 95% CI, 1.02 4.9), CT/CTA abnormalities (hazard ratio, 4.0; 95% CI, 2.0-8.5), and diffusion weighted imaging positivity (hazard ratio, 2.2; 95% CI, 1.05-4.7) predicted recurrent stroke. In the multivariable analysis, only CT/CTA abnormalities predicted recurrent stroke. In a secondary analysis, CT/CTA and MRI were not significantly different in their discriminative value in predicting recurrent stroke (0.67; (95% CI, 0.59-0.76 versus 0.59; 95% CI, 0.52-0.67; P=0.09). CONCLUSIONS: Early assessment of the intracranial and extracranial vasculature using CT/CTA predicts recurrent stroke and clinical outcome in patients with transient ischemic attack and minor stroke. In many institutions, CTA is more readily available than MRI and physicians should access whichever technique is more quickly available at their institution. PMID- 22302110 TI - What the million hearts initiative means for stroke: a presidential advisory from the American Heart Association/American Stroke Association. PMID- 22302111 TI - Cancer stem cells and EMT in carcinoma. AB - The majority of deaths from carcinoma are caused by secondary growths that result from tumour invasion and metastasis. The importance of epithelial-to-mesenchymal transition (EMT) as a driver of invasion and metastasis is increasingly recognised, and recent evidence has highlighted a link between EMT and the cancer stem cells that initiate and maintain tumours and have also been implicated in invasion and metastasis. Here, we review cancer stem cells and their link with EMT, and explore the importance of this link in metastasis and therapeutic resistance of tumours. We also discuss new evidence from our laboratory demonstrating that cancer stem cells display a remarkable phenotypic plasticity that enables them to switch between an epithelial phenotype that drives tumour growth and an EMT phenotype that drives metastasis. As successful therapies must eradicate cancer stem cells in all their guises, the identification of sub-types of cancer stem cells that display therapeutic resistance and phenotypic plasticity has important implications for the future design of therapeutic strategies. The ability to assay the responses of different cancer stem cell phenotypes in vitro holds promise for the rapid development of a new generation of targeted therapies that fulfil this objective. PMID- 22302113 TI - Analysis of the cochlear amplifier fluid pump hypothesis. AB - We use analysis of a realistic three-dimensional finite-element model of the tunnel of Corti (ToC) in the middle turn of the gerbil cochlea tuned to the characteristic frequency (CF) of 4 kHz to show that the anatomical structure of the organ of Corti (OC) is consistent with the hypothesis that the cochlear amplifier functions as a fluid pump. The experimental evidence for the fluid pump is that outer hair cell (OHC) contraction and expansion induce oscillatory flow in the ToC. We show that this oscillatory flow can produce a fluid wave traveling in the ToC and that the outer pillar cells (OPC) do not present a significant barrier to fluid flow into the ToC. The wavelength of the resulting fluid wave launched into the tunnel at the CF is 1.5 mm, which is somewhat longer than the wavelength estimated for the classical traveling wave. This fluid wave propagates at least one wavelength before being significantly attenuated. We also investigated the effect of OPC spacing on fluid flow into the ToC and found that, for physiologically relevant spacing between the OPCs, the impedance estimate is similar to that of the underlying basilar membrane. We conclude that the row of OPCs does not significantly impede fluid exchange between ToC and the space between the row of OPC and the first row of OHC-Dieter's cells complex, and hence does not lead to excessive power loss. The BM displacement resulting from the fluid pumped into the ToC is significant for motion amplification. Our results support the hypothesis that there is an additional source of longitudinal coupling, provided by the ToC, as required in many non-classical models of the cochlear amplifier. PMID- 22302114 TI - Deficits in responding to brief noise offsets in Kcna1 -/- mice reveal a contribution of this gene to precise temporal processing seen previously only for stimulus onsets. AB - The voltage-gated potassium channel subunit Kv1.1 encoded by the Kcna1 gene is expressed in many brainstem nuclei, and electrophysiological studies of Kcna1 null mutant (-/-) single neurons suggest that channels containing this subunit are critical for precise processing of rapid acoustic perturbations. We tested the hypothesis that brief offsets of a background noise are behaviorally less salient for Kcna1 -/- mice, measured by changes in noise offset inhibition of acoustic startle reflexes (ASR). In experiment 1, noise offset was followed by ASR-eliciting sound bursts either after 1-10 ms quiet intervals or after the return of noise for 10-290 ms following 10-ms quiet gaps. ASR inhibition to offset and gaps was initially higher in +/+ mice but persisted longer in -/- mice. Experiment 2 contrasted brief abrupt offsets with ramped offsets of the same duration up to 10 ms, the ramps intended to simulate progressively slower internal decays of afferent processing. Both groups had greater inhibition for abrupt offsets at asymptote, and this difference was evident at the 1-ms interval in +/+ but not -/- mice. Further, the asymptotic effect of ramped offsets in +/+ mice was equal to that produced by abrupt offsets in null mutants, suggesting more perseveration of internal afferent activity following noise offset in -/- mice. Overall, these data are consistent with prior electrophysiological studies showing that the neural mechanisms for processing acoustic transients are less effective in Kcna1 -/- mice and support previous proposals that Kv1.1 contributes to the perception of animal vocalizations and human speech. PMID- 22302115 TI - A lab-on-a-molecule for anions in aqueous solution: using Kolbe electrolysis and radical methylation at iridium for sensing. AB - Iridium complex [(pq)(2)IrCl](2) (1) is established as a quantitatively operating lab-on-a-molecule in aqueous media at physiological pH. Acting as a chemodosimeter, 1 uses two channels, PL and ECL, for the detection of cyanide and acetate, with the former undergoing nucleophilic attack and the latter Kolbe electrolysis and radical-metal combination. PMID- 22302116 TI - The perceived position of moving objects: transcranial magnetic stimulation of area MT+ reduces the flash-lag effect. AB - How does the visual system assign the perceived position of a moving object? This question is surprisingly complex, since sluggish responses of photoreceptors and transmission delays along the visual pathway mean that visual cortex does not have immediate information about a moving object's position. In the flash-lag effect (FLE), a moving object is perceived ahead of an aligned flash. Psychophysical work on this illusion has inspired models for visual localization of moving objects. However, little is known about the underlying neural mechanisms. Here, we investigated the role of neural activity in areas MT+ and V1/V2 in localizing moving objects. Using short trains of repetitive Transcranial Magnetic Stimulation (TMS) or single pulses at different time points, we measured the influence of TMS on the perceived location of a moving object. We found that TMS delivered to MT+ significantly reduced the FLE; single pulse timings revealed a broad temporal tuning with maximum effect for TMS pulses, 200 ms after the flash. Stimulation of V1/V2 did not significantly influence perceived position. Our results demonstrate that area MT+ contributes to the perceptual localization of moving objects and is involved in the integration of position information over a long time window. PMID- 22302117 TI - Contrast-dependent variations in the excitatory classical receptive field and suppressive nonclassical receptive field of cat primary visual cortex. AB - In area V1 of cat and monkey, there is a surround region beyond the classical receptive field (CRF) which alone is unresponsive but may modulate the cell's response. This field is referred to as the "nonclassical receptive field" (nCRF). It has been reported in monkey that the extent of CRF and/or nCRF of V1 neurons is not fixed but varies with stimulus contrast. We reexamined the contrast dependence of V1 neurons in cat to determine whether this differs from previous studies in macaque. By fitting the spatial summation curves obtained at different contrasts with a difference of Gaussians model, we estimated quantitatively the effect of contrast on the spatial extent of the CRF and nCRF as well as the strength of surround suppression. Our results showed that both the CRF and nCRF expanded at low contrast, but the expansion is more marked for the CRF than for the nCRF. Although the effect of contrast on surround suppression was varied, the overall suppression increased significantly at high contrast. Moreover, the contrast-dependent change in the extent of CRF is independent of the change in suppression strength. Overall, our results in cat are in agreement with those obtained in macaque money. PMID- 22302118 TI - Detection and localization of post-operative and post-traumatic bile leak: hybrid SPECT-CT with 99mTc-Mebrofenin. AB - PURPOSE: To evaluate the role of single photon emission tomography-computed tomography (SPECT-CT) with 99mTc-N-(3-bromo-2,4,6-trimethylacetanilide) iminodiacetic acid (Mebrofenin) for detection and localisation of post-operative and post-traumatic bile leak and compare the same with planar hepatobiliary scintigraphy (HBS). METHODS: Data of 32 consecutive patients (Age--35.7 +/- !15.3 years; Female--53.2%) who underwent 99mTc-Mebrofenin planar HBS and SPECT-CT for suspected bile leak was prospectively collected and retrospectively analyzed. Twenty-six patients were post-operative and six had history of abdominal trauma. Planar HBS and SPECTCT images were evaluated by two experienced nuclear medicine physicians. Sensitivity, specificity and predictive values, were calculated for planar HBS and SPECT-CT. Final diagnosis was established based on a combination of re-operative findings, follow up imaging and clinical follow up (1-4 week).For evaluation of observer confidence a third observer used a scoring scale of 1-5, with 1 being definite bile leak and 5 being no leak. Receiver operating characteristic (ROC) curves were drawn and the areas under the curves were compared. RESULTS: The sensitivity, specificity and accuracy of SPECT-CT were 88.8%, 100% and 96.8% while that of planar HBS were 77.7%, 60.8% and 65.6%, respectively. Planar HBS showed very low diagnostic accuracy compared to SPECT-CT (65.6%vs. 96.8%; P = 0.021). It was false positive in nine patients. SPECT-CT also correctly localised the site of bile leak in eight of nine patients. On ROC analysis the observer confidence for SPECT-CT was significantly better than that for planar scintigraphy (P = 0.045). CONCLUSION: 99mTc-Mebrofenin hybrid SPECT-CT is highly sensitive and specific for detection and localisation of post-operative and post-traumatic bile leak. It is more accurate than planar HBS and should be routinely done in such patients. PMID- 22302119 TI - Obscure and occult gastrointestinal bleeding: role of radionuclide imaging. PMID- 22302121 TI - Cross-sectional but not longitudinal association between n-3 fatty acid intake and depressive symptoms: results from the SU.VI.MAX 2 study. AB - Findings regarding the association between n-3 polyunsaturated fatty acid (PUFA) status and depression are conflicting. Thus, the authors studied associations between PUFA intake and depressive symptoms. In 1996, depressive symptoms were assessed in a subsample of participants from the Supplementation with Antioxidant Vitamins and Minerals (SU.VI.MAX) Study using the Center for Epidemiologic Studies Depression Scale (CES-D). In 2007-2009, information on CES-D score, history of depression, and use of antidepressant medication was obtained. Intakes of n-3 PUFAs were estimated from repeated 24-hour dietary records collected during 1994-1996. Subjects with depressive symptoms (cases) were identified using CES-D scores greater than 15 and/or antidepressant use. Logistic regression analyses were used. Cross-sectional (n = 2,744) and longitudinal (n = 1,235) associations between quartiles of PUFA intake and depressive symptoms were estimated. In cross-sectional analyses, quartile of n-3 PUFA intake was associated with lower odds of depressive symptoms (fourth quartile vs. first: odds ratio = 0.74, 95% confidence interval: 0.58, 0.95; P for trend = 0.001). No association between PUFA intake and incidence of depressive symptoms over 13 years was detected. This study provides new insights into the PUFA-depression link. While no association between n-3 PUFA intake and incidence of depressive symptoms was detected, an association was observed in cross-sectional analyses, which may reflect unhealthy dietary patterns among subjects with depressive symptoms. PMID- 22302120 TI - Relation of blood cadmium, lead, and mercury levels to biomarkers of lipid peroxidation in premenopausal women. AB - Exposures to cadmium, lead, and mercury are associated with adverse health effects, including cardiovascular disease, which may be promoted by lipid peroxidation. The authors examined cadmium, lead, and mercury in relation to plasma levels of F(2)-8alpha isoprostanes (isoprostane), 9-hydroperoxy-10,12 octadecadienoic acid (9-HODE), 13-hydroxy-9,11-octadecadienoic acid (13-HODE), and thiobarbituric acid reactive substances (TBARS) in 252 women from western New York State (2005-2007). Healthy premenopausal women were followed for <=2 menstrual cycles, with biomarkers of lipid peroxidation being assessed <=8 times per cycle. Metals were measured at baseline in whole blood. Linear mixed models were used to estimate the association between cadmium, lead, and mercury and lipid peroxidation biomarkers. Median cadmium, lead, and mercury levels were 0.30 MUg/L, 0.86 MUg/dL, and 1.10 MUg/L, respectively. Blood cadmium, lead, and mercury were not associated with increases in isoprostane, TBARS, 9-HODE, or 13 HODE levels. Isoprostane levels decreased 6.80% (95% confidence interval: -10.40, -3.20) per 1% increase in mercury. However, after adjustment for a simulated strong confounding factor, such as precisely measured fish consumption, the observed association was attenuated, suggesting that this unexpected association could be attributable to unmeasured confounding. In this population of healthy premenopausal women with low exposure levels, cadmium, lead, and mercury were not associated with elevated lipid peroxidation biomarkers. PMID- 22302122 TI - Genotoxic potential of methyleugenol and selected methyleugenol metabolites in cultured Chinese hamster V79 cells. AB - Methyleugenol is a substituted alkenylbenzene classified by the European Union's Scientific Committee on Food as a genotoxic carcinogen. We addressed cytotoxicity, genotoxicity and mutagenicity caused by methyleugenol and selected oxidative methyleugenol metabolites in Chinese hamster lung fibroblasts V79 cells. Cytotoxicity was measured by two cell proliferation assays, water soluble tetrazolium salt (WST) 1 and sulforhodamine B (SRB) assays. Genotoxicity was determined by using single cell gel electrophoreses (comet assay) and the in vitro micronuclei test, while mutagenicity was investigated with the hypoxanthinephosphoribosyl transferase (hprt) assay. Methyleugenol and 1' hydroxymethyleugenol showed no or marginal cytotoxic effects, but caused DNA strand breaks at concentrations >=10 MUM. The metabolites methyleugenol-2',3' epoxide and 3'-oxomethylisoeugenol exhibited growth inhibitory properties with IC(50)-values of 70-90 MUM after 48 h or 72 h of incubation. These metabolites significantly enhanced cytotoxicity and DNA damage after 1 h of incubation. Overall, no increase in formamidopyrimidine DNA glycosylase sensitive sites were detected with the comet assay. The metabolites 1'-hydroxymethyleugenol and methyleugenol-2',3'-epoxide exceeded the DNA strand breaking properties of the parent compound methyleugenol. However, only 3'-oxomethylisoeugenol and methyleugenol-2',3'-epoxide induced the formation of micronucleated cells in comparison to the negative control. These compounds were found to be not or rather weakly mutagenic at the hprt locus. In summary, phase I metabolites exceeded the cytotoxic and genotoxic properties of the parent compound methyleugenol. PMID- 22302123 TI - New trinuclear metal string complexes containing rigid Hdzp ligands: synthesis, structure, magnetism and DFT calculation (Hdzp = 1,9-diazaphenoxazine). AB - The synthesis, crystal structure, magnetic properties, and single-molecule conductance of two new trinuclear metal string complexes, [Ni(3)(dzp)(4)(NCS)(2)] (2) and [Co(3)(dzp)(4)(NCS)(2)] (3), containing the rigid Hdzp ligand (1, 1,9 diazaphenoxazine) are reported. X-ray structural analyses show that compounds 2 and 3 exhibit smaller torsion angles and longer metal-metal distances than those exhibited by the corresponding dpa(-) analogues (dpa(-) = dipyridylamido anion) due to the rigidity of Hdzp ligands. The longer metal-metal distance observed for 2 and 3 results in variations in their magnetic properties. The exchange interaction (J = -160 cm(-1)) between two high spin (HS) Ni(II) ions in 2 decreases slightly in comparison with those of trinickel dpa(-) analogues. The doublet-quartet gap of 3 is smaller than that of [Co(3)(dpa)(4)(NCS)(2)] (4), which causes compound 3 to show spin-crossover behavior even at low temperature. PMID- 22302126 TI - The stable cyclic adenosine monophosphate analogue, dibutyryl cyclo-adenosine monophosphate (bucladesine), is active in a model of acute skin inflammation. AB - Anti-inflammatory therapeutic options for the topical treatment of skin diseases with inflammatory or allergic contribution are mostly limited to topical glucocorticoids and calcineurin inhibitors. Both compound classes induce adverse effects. Elevation of intracellular cyclic adenosine monophosphate (cAMP) by inhibition of phosphodiesterase 4 was shown to induce potent anti-inflammatory effects, but the safety profile of currently available compounds is not sufficient. A different approach to increase intracellular cAMP is the substitution of chemically stabilized cAMP analogues. Bucladesine is a stabilized cAMP analogue with an excellent safety profile which had been marketed as topical treatment of impaired wound healing. In the current study, a novel water free emulsion containing bucladesine was evaluated for anti-inflammatory effects. In the arachidonic acid induced ear oedema model in mice, single or multiple administration of an emulsion containing 1.5% was capable of significantly reducing the inflammatory oedema. The data indicate that bucladesine represents an interesting treatment option for skin diseases where an anti-inflammatory activity is indicated. Due to the established clinical safety, this agent may bridge the gap between potent agents such as glucocorticoids or calcineurin inhibitors and emollients without active compounds. PMID- 22302127 TI - Absolute oral bioavailability of almorexant, a dual orexin receptor antagonist, in healthy human subjects. AB - BACKGROUND/AIMS: The aim of this single-center, open-label study was to assess the absolute bioavailability of an oral (tablet) versus intravenous formulation of almorexant in healthy subjects. METHODS: A pilot phase in 3 healthy male subjects, which preceded the main study, consisted of a single 30-min intravenous infusion of 10 mg almorexant. Its objectives were to ensure the tolerability of the intravenous formulation and to select the intravenous dose for the main study. The main study was a randomized, two-way crossover study in 20 healthy subjects (10 males and 10 females). Subjects received a single oral dose of 200 mg almorexant and a single 30-min intravenous infusion of 20 mg almorexant. RESULTS: All 23 subjects completed the study as planned. Almorexant was well tolerated; the main observed adverse events were somnolence and fatigue. A geometric mean total body clearance of 43 l/h (95% CI 39-47) and a volume of distribution of 683 liters (95% CI 552-845) were determined. The absolute oral bioavailability of almorexant was 11.2% (90% CI 9.6-13.1). CONCLUSION: Almorexant seems to possess a pronounced first-pass effect and metabolism. PMID- 22302128 TI - Double cervical ostia after large loop excision of transformation zone. AB - BACKGROUND: Large loop excision of the transformation zone (LLETZ) is the preferred treatment modality among colposcopists for cervical intraepithelial neoplasia. We report a unique case of cervical septum after LLETZ and the subsequent management. CASE: Large loop excision of the transformation zone was performed on a young woman for a severely dyskaryotic cervical smear and colposcopic impression of high-grade abnormality. At her 6-month follow-up, double cervical ostium was seen resulting from cervical septum formation. This was surgically divided to enable a single cervical ostium for future smear taking and follow-up. CONCLUSIONS: This case report is to make clinicians aware of a rare complication such as double cervical ostium after LLETZ and its management. PMID- 22302129 TI - Benign papular lesions of the vulva. AB - The vulva may develop conditions more familiar to dermatologists than to gynecologists. Although gynecologists may be familiar with some of these lesions, a review of these benign and often pruritic papular lesions may be helpful when receiving a diagnosis more commonly seen in dermatologic practice. PMID- 22302130 TI - Conservative treatment of microinvasive adenocarcinoma of uterine cervix: long term follow-up. AB - OBIECTIVE: This study aimed to evaluate the safety of conservative treatment in women desiring preservation of fertility with stage IA adenocarcinoma of the cervix. MATERIALS AND METHODS: Clinical report of all women with stage IA adenocarcinoma of the cervix, endocervical subtype, with clear margins on cone biopsy, diagnosed in our cancer center inclusive between January 1995 and December 2007, were evaluated, after either conservative therapy or hysterectomy. All diagnoses were reviewed by a pathologist expert in gynecologic oncology. Follow-up methods include at least cervical cytology, colposcopy with direct biopsy if indicated, and cervical curettage. RESULTS: Of 783 laser cone biopsy specimens, 7 were diagnostic for microinvasive adenocarcinoma, endocervical subtype (6 stage IA1 lesions and 1 stage IA2 lesion) with clear margins. No lymphovascular space invasion was seen. No residual invasive disease was observed in the specimens of 2 patients treated with hysterectomy after conization. Five women treated with laser cone biopsy only are free of invasive disease at 44, 66, 72, 86 and 100 months; 1 patient was found to have persistent adenocarcinoma in situ on endocervical cytology. CONCLUSIONS: Cone biopsy as definitive therapy is safe in women with stage IA1 adenocarcinoma of the cervix, endocervical subtype, with clear margins and no lymphovascular space invasion. Because of the low reliability of follow-up techniques (cytology, colposcopy, and endocervical curettage), conservative treatment should be reserved only for women strongly desiring to preserve fertility and accepting the risk of recurrent disease. PMID- 22302131 TI - Regulation of genes involved in nitrogen utilization on different C/N ratios and nitrogen sources in the model ectomycorrhizal fungus Hebeloma cylindrosporum. AB - Nitrogen (N) utilization by ectomycorrhizal fungi is an essential aspect of their ecosystem function. N deposition changes both the N pools and the carbon/nitrogen (C/N) ratio of the substrates where ectomycorrhizal fungi are found, and it is important to understand how these changes affect the N forms used by ectomycorrhizal fungi. To overcome the difficulties of studying ectomycorrhizal fungi in situ, we investigated all known N genes in the model fungus, Hebeloma cylindrosporum in a culture study. In addition to studying the regulation of all known N utilization genes, we aimed to understand whether there are gene clusters that undergo similar regulation. Lastly we studied how C/N ratio, N transporter type, and N source affected relative gene expression levels. We grew the D2 strain of H. cylindrosporum on a range of inorganic and organic N sources under low, medium, and high C/N ratios. We found three gene clusters that were regulated in a similar pattern. Lastly, we found C/N ratio, N source and N transporter type all affected gene expression levels. Relative expression levels were highest on the high C/N ratio, BSA and diLeucine N sources, and inorganic N transporters were always expressed at higher levels than organic N transporters. These results suggest that inorganic N sources may always the default preference for H. cylindrosporum, regardless of both the N sources and the C/N ratio of the substrate. PMID- 22302132 TI - The dependence of alpha-tocopheroxyl radical reduction by hydroxy-2,3 diarylxanthones on structure and micro-environment. AB - The flavonoid quercetin is known to reduce the alpha-tocopheroxyl radical (TocO) and reconstitute alpha-tocopherol (TocOH). Structurally related polyphenolic compounds, hydroxy-2,3-diarylxanthones (XH), exhibit antioxidant activity which exceeds that of quercetin in biological systems. In the present study repair of TocO by a series of these XH has been evaluated using pulse radiolysis. It has been shown that, among the studied XH, only 2,3-bis(3,4-dihydroxyphenyl)-9H xanthen-9-one (XH9) reduces TocO, though repair depends strongly on the micro environment. In cationic cetyltrimethylammonium bromide (CTAB) micelles, 30% of TocO radicals are repaired at a rate constant of ~7.4 * 10(6) M(-1) s(-1) by XH9 compared to 1.7 * 10(7) M(-1) s(-1) by ascorbate. Water-soluble Trolox (TrOH) radicals (TrO) are restored by XH9 in CTAB (rate constant ~3 * 10(4) M(-1) s(-1)) but not in neutral TX100 micelles where only 15% of TocO are repaired (rate constant ~4.5 * 10(5) M(-1) s(-1)). In basic aqueous solutions TrO is readily reduced by deprotonated XH9 species leading to ionized XH9 radical species (radical pK(a) ~10). An equilibrium is observed (K = 130) yielding an estimate of 130 mV for the reduction potential of the [X9,H(+)/XH9] couple at pH 11, lower than the 250 mV for the [TrO,H(+)/TrOH] couple. A comparable value (100 mV) has been determined by cyclic voltammetry measurements. PMID- 22302133 TI - Interleukin-1beta enhances the production of soluble MICA in human hepatocellular carcinoma. AB - The production of soluble major histocompatibility complex class I-related chain A (MICA) is thought to antagonize NKG2D-mediated immunosurveillance. Interleukin 1beta (IL-1beta) is elevated in patients with chronic hepatitis C (CH), and this might contribute to the escape of hepatocellular carcinoma (HCC) cells from innate immunity. In this study, we investigated the immunoregulatory role of IL 1beta in the production of soluble MICA of HCC cells. First, we investigated the correlation between the serum IL-1beta levels and soluble MICA in CH patients. Serum IL-1beta levels were associated with soluble MICA levels in CH patients. The serum IL-1beta levels of CH patients with the HCC occurrence were significantly higher than those of CH patients without HCC. We next examined the MICA production of IL-1beta-treated HCC cells. Addition of IL-1beta resulted in significant increase in the production of soluble MICA in HepG2 and PLC/PRF/5 cells, human HCC cells. But soluble MICA was not detected in both non-treated and IL-1beta-treated normal hepatocytes. Addition of IL-1beta did not increase the expressions of membrane-bound MICA on HCC cells. These were observed similarly in various cancer cells including a gastric cancer (MKN1), two colon cancers (HCT116 and HT29) and a cervical cancer (HeLa). Addition of IL-1beta also increased the expression of a disintegrin and metalloproteinase (ADAM)9 in HCC cells, and the knockdown of ADAM9 in IL-1beta-treated HCC cells resulted in the decrease in the production of soluble MICA of HCC cells. These findings indicate that IL-1beta might enhance the production of soluble MICA by activating ADAM9 in human HCC. PMID- 22302134 TI - Triply ferrocene-bridged boroxine cyclophane. AB - Mild solvothermal dehydration of 1,1'-ferrocenediboronic acid produces a triply ferrocene-bridged boroxine cyclophane. Its crystal structure reveals a rigid trigonal prism that presents a minimal boroxine-based covalent organic polyhedron (COP). PMID- 22302136 TI - Clinical and radiographic results from a 2-year comparison of once-weekly versus twice-weekly administration of etanercept in biologics-naive patients with rheumatoid arthritis. AB - OBJECTIVES: The twice-weekly administration of 25 mg of etanercept (TW) has been shown to be effective in patients with rheumatoid arthritis (RA). However, the once-weekly administration of 25 mg of etanercept (OW) was tried in order to address the economic burden of anti-rheumatic biologics. We evaluated the clinical and radiographic results from a 2-year follow-up study of patients receiving OW or TW. METHODS: Sixty-three biologics-naive patients with RA were randomly assigned to receive either OW (n = 42) or TW (n = 21). RESULTS: From baseline to year 2, rates of clinical remission,according to the Disease Activity Score of 28 joints(DAS-28) (based on C-reactive protein; CRP)-with clinical remission being regarded as a DAS-28 (CRP) score of?2.3-were significantly improved in the OW group (from 1.6 to 39.0%) and in the TW group (from 9.5 to 47.6%),but no significant between-group difference was observed at year 2. Radiographic joint damage, quantified with the modified Sharp score, was significantly progressive in the OW group in contrast to findings in the TW group. Thus,among patients receiving TW therapy, the progression of joint damage may have been inhibited or may have shown remission. CONCLUSIONS: These results suggest that, in terms of DAS-28 remission, OW therapy can efficiently substitute for TW therapy in biologics-naive patients with RA. However, TW therapy was indispensable in preventing the worsening of joint damage. PMID- 22302137 TI - The effect of micronutrient supplements on female fertility: a systematic review. AB - PURPOSE: Assessment of the influence of vitamins, trace elements and multivitamin supplements on female fertility. METHODS: Systematic review of published controlled trials and cohort studies investigating the effect of vitamin supplements on female fertility. 13 studies with a total of 90,004 female test persons and patients. INCLUSION CRITERIA: oral, preconceptional administration of single or combination of vitamin supplements; EXCLUSION CRITERIA: experimental studies, pharmacological studies, case control studies, case reports, reviews, meta-analysis. Women with chronic diseases, genetic or physical causes for (primary) sterility, couples with an impaired fertility of both partners; patients undergoing reproductive medicine care (insemination, in vitro fertilization, IVF, intracytoplasmatic sperm injection, ICSI). Determination of the proportion of women that experienced an influence of vitamin supplements on their fertility. RESULTS: Thirteen relevant trials out of 37 studies were included. Some studies suggest a possible effect of micronutrients on female fertility. Emphasized results, for example, were an association between multivitamin substitution on pregnancy rate as well as higher vitamin B6 levels in fertile women compared to infertile women. One randomised controlled study showed a positive effect of vitamin C in women with luteal insufficiency. CONCLUSION: Although some studies suggest possible effects of micronutrients on female fertility general recommendations are not possible since all studies had methodological or statistical limitations. Further investigations using evidence based criteria are necessary to analyze and to confirm these non-evident appearances. PMID- 22302138 TI - Prolonged propriospinal myoclonus following spinal anesthesia for cesarean section: case report and literature review. PMID- 22302139 TI - Effects of ecstasy/polydrug use on memory for associative information. AB - RATIONALE: Associative learning underpins behaviours that are fundamental to the everyday functioning of the individual. Evidence pointing to learning deficits in recreational drug users merits further examination. OBJECTIVES: A word pair learning task was administered to examine associative learning processes in ecstasy/polydrug users. METHODS: After assignment to either single or divided attention conditions, 44 ecstasy/polydrug users and 48 non-users were presented with 80 word pairs at encoding. Following this, four types of stimuli were presented at the recognition phase: the words as originally paired (old pairs), previously presented words in different pairings (conjunction pairs), old words paired with new words, and pairs of new words (not presented previously). The task was to identify which of the stimuli were intact old pairs. RESULTS: Ecstasy/ploydrug users produced significantly more false-positive responses overall compared to non-users. Increased long-term frequency of ecstasy use was positively associated with the propensity to produce false-positive responses. It was also associated with a more liberal signal detection theory decision criterion value. Measures of long term and recent cannabis use were also associated with these same word pair learning outcome measures. Conjunction word pairs, irrespective of drug use, generated the highest level of false-positive responses and significantly more false-positive responses were made in the divided attention condition compared to the single attention condition. CONCLUSIONS: Overall, the results suggest that long-term ecstasy exposure may induce a deficit in associative learning and this may be in part a consequence of users adopting a more liberal decision criterion value. PMID- 22302140 TI - Dinickel(II) complexes: preparation and catalytic activity. AB - Ligands (L(a-c)) based on 2,7-bis(3,5-di-R-pyrazol-1-yl)-1,8-naphthyridine (a, R = H; b, R = CH(3); c, R = Ph) were prepared for the construction of a series of dinickel complexes. Treatment of L(x) with NiCl(2) in an anhydrous methanol/THF solution resulted in the formation of dinuclear complexes [(L(x))(MU Cl)(2)Ni(2)Cl(2)(CH(3)OH)(2)] (3, x = a; 4, x = b; 5, x = c). These new complexes were characterized by elemental analysis, IR and UV-Vis spectroscopic techniques. The structures of complexes 3 and 4 were further confirmed by X-ray diffraction studies. Interestingly, crystals of 4 were obtained as a co-crystallization of 4 and the methanol substituted species [{(L(b))(MU-Cl)(2)Ni(2)Cl(CH(3)OH)(3)}Cl] (4'). These dinickel complexes have been tested in the catalytic homo-coupling of terminal alkynes with the use O(2) as the oxidant, showing excellent activities. A clear improvement on the catalytic activity of these complexes is observed as compared to the mono-nuclear species. PMID- 22302142 TI - The EigenfactorTM Score in highly specific medical fields: the dental model. AB - We sought to compare the Eigenfactor ScoreTM journal rank with the journal Impact Factor over five years, and to identify variables that may influence the ranking differences between the two metrics. Datasets were retrieved from the Thomson Reuters((r)) and Eigenfactor ScoreTM Web sites. Dentistry was identified as the most specific medical specialty. Variables were retrieved from the selected journals to be included in a regression linear model. Among the 46 dental journals included in the analysis, striking variations in ranks were observed according to the metric used. The Bland-Altman plot showed a poor agreement between the metrics. The multivariate analysis indicates that the number of original research articles, the number of reviews, the self-citations, and the citing time may explain the differences between ranks. The Eigenfactor ScoreTM seems to better capture the prestige of a journal than the Impact Factor. In medicine, the bibliometric indicators should focus not only on the overall medical field but also on specialized disciplinary fields. Distinct measures are needed to better describe the scientific impact of specialized medical publications. PMID- 22302143 TI - Noggin is required for early development of murine upper incisors. AB - BMP signaling plays crucial roles in the development of many organs, including the tooth. Equally important is BMP signaling homeostasis, as demonstrated by multiple organ defects in mice lacking the extracellular BMP antagonist Noggin. Here, we show that Noggin is initially expressed in the maxillary mesenchyme adjunct to the upper incisor at the initiation stage, and then in the developing teeth, including incisors and molars, from the bud stage. Noggin mutants develop normal molars and mandibular incisors, but form a single, medially located upper incisor that is arrested at the late bud stage. Histological and molecular marker analyses demonstrated that two distinct upper incisor placodes initiate independently at E11.5, but begin to fuse at E12.5, coupling with elevated cell proliferation rates in the developing tooth germs. We further found that Chordin and Gremlin, two other BMP antagonists, are co-expressed with Noggin in the developing lower incisor and molar teeth. These observations indicate the importance of BMP signaling homeostasis, and suggest a functional redundancy between BMP antagonists during tooth development. PMID- 22302144 TI - Control of cytokine mRNA expression by RNA-binding proteins and microRNAs. AB - Cytokines are critical mediators of inflammation and host defenses. Regulation of cytokines can occur at various stages of gene expression, including transcription, mRNA export, and post- transcriptional and translational levels. Among these modes of regulation, post-transcriptional regulation has been shown to play a vital role in controlling the expression of cytokines by modulating mRNA stability. The stability of cytokine mRNAs, including TNFalpha, IL-6, and IL 8, has been reported to be altered by the presence of AU-rich elements (AREs) located in the 3'-untranslated regions (3'UTRs) of the mRNAs. Numerous RNA binding proteins and microRNAs bind to these 3'UTRs to regulate the stability and/or translation of the mRNAs. Thus, this paper describes the cooperative function between RNA-binding proteins and miRNAs and how they regulate AU-rich elements containing cytokine mRNA stability/degradation and translation. These mRNA control mechanisms can potentially influence inflammation as it relates to oral biology, including periodontal diseases and oral pharyngeal cancer progression. PMID- 22302145 TI - Self-assembled Nano-layering at the Adhesive interface. AB - According to the 'Adhesion-Decalcification' concept, specific functional monomers within dental adhesives can ionically interact with hydroxyapatite (HAp). Such ionic bonding has been demonstrated for 10-methacryloyloxydecyl dihydrogen phosphate (MDP) to manifest in the form of self-assembled 'nano-layering'. However, it remained to be explored if such nano-layering also occurs on tooth tissue when commercial MDP-containing adhesives (Clearfil SE Bond, Kuraray; Scotchbond Universal, 3M ESPE) were applied following common clinical application protocols. We therefore characterized adhesive-dentin interfaces chemically, using x-ray diffraction (XRD) and energy-dispersive x-ray spectroscopy (EDS), and ultrastructurally, using (scanning) transmission electron microscopy (TEM/STEM). Both adhesives revealed nano-layering at the adhesive interface, not only within the hybrid layer but also, particularly for Clearfil SE Bond (Kuraray), extending into the adhesive layer. Since such self-assembled nano-layering of two 10-MDP molecules, joined by stable MDP-Ca salt formation, must make the adhesive interface more resistant to biodegradation, it may well explain the documented favorable clinical longevity of bonds produced by 10-MDP-based adhesives. PMID- 22302146 TI - Effects of Candesartan on Left Ventricular Function, Aldosterone and BNP in Chronic Heart Failure. AB - PURPOSE: Heart failure (HF) is characterized by activation of neurohormonal systems such as aldosterone and natriuretic peptides. In the absence of published data, CandHeart trial was designed to assess the effects on left ventricular (LV) function, aldosterone and brain natriuretic peptide (BNP) of candesartan in patients with HF and preserved (LVEF >= 40%) or depressed (LVEF <40%) LV systolic function. METHODS: A total of 514 patients with stable symptomatic NYHA II-IV HF and any left ventricular ejection fraction (LVEF)were randomized to candesartan (target dose 32 mg once daily) as add-on therapy or standard medical therapy alone. Standardized echocardiographic exams were performed locally under central quality control, whereas biomarkers were assayed in a core laboratory. RESULTS: The majority of patients (73.3%) were NYHA II and on ACE inhibitors (91.8%) and beta-blockers (85.4%). Mean age was 66 +/- 11 years. Mean LVEF was 36.2 +/- 9.7% and 24.9% of patients had LVEF >= 40%. LVEF increased significantly more in the candesartan group (p = 0.09 at 12 weeks and p = 0.01 at 48 weeks) and left ventricular end-diastolic diameter decreased in candesartan group (p = 0.05 at 12 weeks). Candesartan significantly reduced aldosterone at 48 weeks (p = 0.009). BNP was reduced similarly over time in both study groups (p = 0.35 and p = 0.98 at 12 and 48 weeks, respectively). There were 6.6% of discontinuations of candesartan for adverse events. CONCLUSIONS: In CandHeart, the addition of candesartan to standard medical treatment did not reduce circulating BNP more than standard therapy (primary endpoint), but it significantly improved LV function and produced a marked decrease in aldosterone levels at study end. PMID- 22302147 TI - cn.MOPS: mixture of Poissons for discovering copy number variations in next generation sequencing data with a low false discovery rate. AB - Quantitative analyses of next-generation sequencing (NGS) data, such as the detection of copy number variations (CNVs), remain challenging. Current methods detect CNVs as changes in the depth of coverage along chromosomes. Technological or genomic variations in the depth of coverage thus lead to a high false discovery rate (FDR), even upon correction for GC content. In the context of association studies between CNVs and disease, a high FDR means many false CNVs, thereby decreasing the discovery power of the study after correction for multiple testing. We propose 'Copy Number estimation by a Mixture Of PoissonS' (cn.MOPS), a data processing pipeline for CNV detection in NGS data. In contrast to previous approaches, cn.MOPS incorporates modeling of depths of coverage across samples at each genomic position. Therefore, cn.MOPS is not affected by read count variations along chromosomes. Using a Bayesian approach, cn.MOPS decomposes variations in the depth of coverage across samples into integer copy numbers and noise by means of its mixture components and Poisson distributions, respectively. The noise estimate allows for reducing the FDR by filtering out detections having high noise that are likely to be false detections. We compared cn.MOPS with the five most popular methods for CNV detection in NGS data using four benchmark datasets: (i) simulated data, (ii) NGS data from a male HapMap individual with implanted CNVs from the X chromosome, (iii) data from HapMap individuals with known CNVs, (iv) high coverage data from the 1000 Genomes Project. cn.MOPS outperformed its five competitors in terms of precision (1-FDR) and recall for both gains and losses in all benchmark data sets. The software cn.MOPS is publicly available as an R package at http://www.bioinf.jku.at/software/cnmops/ and at Bioconductor. PMID- 22302148 TI - A subgroup of SGS3-like proteins act redundantly in RNA-directed DNA methylation. AB - Plant specific SGS3-like proteins are composed of various combinations of an RNA binding XS domain, a zinc-finger zf-XS domain, a coil-coil domain and a domain of unknown function called XH. In addition to being involved in de novo 2 (IDN2) and SGS3, the Arabidopsis genome encodes 12 uncharacterized SGS3-like proteins. Here, we show that a group of SGS3-like proteins act redundantly in RNA-directed DNA methylation (RdDM) pathway in Arabidopsis. Transcriptome co-expression analyses reveal significantly correlated expression of two SGS3-like proteins, factor of DNA methylation 1 (FDM1) and FDM2 with known genes required for RdDM. The fdm1 and fdm2 double mutations but not the fdm1 or fdm2 single mutations significantly impair DNA methylation at RdDM loci, release transcriptional gene silencing and dramatically reduce the abundance of siRNAs originated from high copy number repeats or transposons. Like IDN2 and SGS3, FDM1 binds dsRNAs with 5' overhangs. Double mutant analyses also reveal that IDN2 and three uncharacterized SGS3-like proteins FDM3, FDM4 and FDM5 have overlapping function with FDM1 in RdDM. Five FDM proteins and IDN2 define a group of SGS3-like proteins that possess all four signature motifs in Arabidopsis. Thus, our results demonstrate that this group of SGS3-like proteins is an important component of RdDM. This study further enhances our understanding of the SGS3 gene family and the RdDM pathway. PMID- 22302149 TI - Perceptions of social support, empowerment and youth risk behaviors. AB - This study examined the association of perceived social support and community empowerment among urban middle-school students living in Matamoros, Mexico and the risk behaviors of fighting, alcohol and tobacco use, and sexual activity. Middle school students (n = 1,181) from 32 public and private Mexican schools were surveyed. Weighted multiple logistic regression analyses were conducted. Among girls, lack of parent/teacher interactions regarding school increased odds for fighting, alcohol and tobacco use. Among boys, lack of empowerment increased odds of alcohol and tobacco use and lack of parent/teacher interactions regarding school increased odds for sexual activity. Community empowerment and perceived social support are uniquely associated with risk behaviors for girls and boys. Additionally, perceived social support from individuals most immediate to the youth are associated with protection against risk for some behaviors, while perceived social support from individuals more removed from youth have mixed association with risk behaviors. PMID- 22302150 TI - Antimigraine (low-amine) diet may be helpful in children with cyclic vomiting syndrome. PMID- 22302151 TI - Bioinformatic software for cerebrospinal fluid spectrophotometry in suspected subarachnoid haemorrhage. AB - BACKGROUND: Diagnosis of subarachnoid haemorrhage (SAH) is firstly based on imaging and secondly on spectrophotometry. Bilirubin may be detected in the cerebrospinal fluid (CSF) for up to two weeks after SAH. CSF pigment analysis is commonly performed according to the Chalmers manual technique but may be prone to operator error. We propose an online software solution, based on the United Kingdom National External Quality Assessment Service (UKNEQAS) recommendations, to support the interpretation of CSF pigment analysis. METHODS: Based on the manual Chalmers technique, we have developed a web application (in Personal Home Page language including JpGraph module and an Oracle database((r))) that enables the calculation of net oxyhaemoglobin absorbance and net bilirubin absorbance. It uses data from the CSF spectrophotometry, CSF and serum protein concentrations, and serum bilirubin concentration to provide an interpretation based on the NEQAS decision tree. The application was retrospectively validated using the spectra from 350 patients, previously analysed by the manual method. RESULTS: In total, 91.1% interpretations from spectra analysed with the web application were in accordance with the results obtained manually. The 8.9% discordant results were mostly related to an incorrect interpretation using the manual technique. CONCLUSIONS: The software developed in our laboratory to interpret CSF pigment analysis results is a precise, robust and useful tool that allows reproducible conclusions to be drawn. This software is available through a web interface. PMID- 22302152 TI - Screening for metabolic vitamin B12 deficiency by holotranscobalamin in patients suspected of vitamin B12 deficiency: a multicentre study. AB - BACKGROUND: Vitamin B(12) deficiency occurs frequently, especially among the elderly. However, screening for vitamin B(12) deficiency is hampered by poor sensitivity of the existing total vitamin B(12) assay. Methylmalonic acid (MMA) is considered as the most representative indicator of metabolic vitamin B(12) deficiency and is used as such in this study. The aim of this study was to validate the clinical usefulness of holotranscobalamin (holoTC) as an initial screening assay for metabolic vitamin B(12) deficiency in a mixed patient population. METHODS: Three hundred and sixty blood samples were collected by five Dutch hospitals. Vitamin B(12) and holoTC in serum were measured (AxSYM; Abbott). MMA in serum was measured by tandem mass spectrometry (LC-MS/MS). RESULTS: Receiver operating curve (ROC) analysis demonstrated a greater area under the curve (AUC) for holoTC than for vitamin B(12) in detecting vitamin B(12) deficiency characterized by three predefined cut-off levels of MMA. A cut-off value of 32 pmol/L of holoTC resulted in the highest sensitivity (83%) with acceptable specificity (60%) in detecting MMA concentrations above 0.45 MUmol/L. The combination of vitamin B(12) and holoTC did not improve diagnostic accuracy at this cut-off level. CONCLUSIONS: HoloTC has a better diagnostic accuracy than vitamin B(12) and can replace the existing vitamin B(12) assay as a primary screening test in patients suspected of vitamin B(12) deficiency. Critical evaluation of cut-off values of holoTC indicated that a cut-off value of 32 pmol/L can be considered in screening for metabolic vitamin B(12) deficiency (defined by MMA > 0.45MUmol/L) in a mixed patient population. PMID- 22302153 TI - Monitoring of atmospheric nitrogen dioxide by long-path pulsed differential optical absorption spectroscopy using two different light paths. AB - Measurements of the local distribution of atmospheric nitrogen dioxide (NO(2)) by long-path pulsed differential optical absorption spectroscopy (LP-PDOAS) in Tokyo during August 2008 are presented. Two LP-PDOAS systems simultaneously measured average NO(2) temporal mixing ratios along two different paths from a single observation point. Two flashing aviation obstruction lights, located 7.0 km north and 6.3 km east from the observation point, were used as light sources, allowing spatiotemporal variations of NO(2) in Tokyo to be inferred. The LP-PDOAS data were compared with ground-based data measured using chemiluminescence. Surface wind data indicated that large inhomogeneities were present in the spatial NO(2) distributions under southerly wind conditions, while northerly wind conditions displayed greater homogeneity between the two systems. The higher correlation in the NO(2) mixing ratio between the two LP-PDOAS systems was observed under northerly wind conditions with a correlation factor R(2) = 0.88. We demonstrated that the combined deployment of two LP-PDOAS systems oriented in different directions provides detailed information on the spatial distribution of NO(2). PMID- 22302154 TI - Gold nanoparticle based signal enhancement liquid crystal biosensors for DNA hybridization assays. AB - A novel signal enhanced liquid crystal biosensor based on using AuNPs for highly sensitive DNA detection has been developed. This biosensor not only significantly decreases the detection limit, but also offers a simple detection process and shows a good selectivity to distinguish perfectly matched target DNA from two base mismatched DNA. PMID- 22302155 TI - The role of congruency in retronasal odor referral to the mouth. AB - Referral of retronasal odors to the mouth is a fundamental phenomenon of flavor perception. A previous study from this laboratory provided evidence that, contrary to prior speculation, taste rather than touch was the primary factor in retronasal odor referral. The present study further investigated this question by studying the role of congruency between taste and odor on retronasal odor referral under conditions that mimicked natural food consumption. Subjects performed odor localization tasks after sampling gelatin stimuli that contained various congruent and incongruent tastes-odor combinations. The results showed that when a congruent taste was added, referral to the oral cavity and tongue were significantly enhanced. In addition, the data also indicate that the degree of congruency between taste and odor may modulate the degree of odor referral to the mouth. These findings suggest that odor referral is maximized when congruent flavor dimensions are combined to trigger perceptual "flavor objects" that represent known or potential foods. The results are discussed in terms of the factors that play a role in the retronasal odor referral as well as the potential neural mechanisms that may underlie it. PMID- 22302156 TI - Mammalian-specific OR37 receptors are differentially activated by distinct odorous fatty aldehydes. AB - The capacity of the mammalian olfactory system to detect an enormous collection of different chemical compounds is based on a large repertoire of odorant receptors (ORs). A small group of these ORs, the OR37 family, is unique due to a variety of special features. Members of this subfamily are exclusively found in mammals, they share a high degree of sequence homology and are highly conserved during evolution. It is still elusive which odorants may activate these atypical receptors. We have reasoned that compounds from skin, hairs, or skin glands might be potential candidates. We have exposed mice to such compounds and monitored activation of glomeruli through the expression of the activity marker c-fos in juxtaglomerular cells surrounding ventrally positioned glomeruli in the olfactory bulb (OB). Employing this methodology it was found that stimulation with long chain alkanes elicits activation in the ventral part of the OB, however, none of the OR37 glomeruli. Analyses of long-chain hydrocarbon compounds with different functional groups revealed that long-chain aliphatic aldehydes elicited an activation of defined OR37 glomeruli, each of them responding preferentially to an aldehyde with different chain lengths. These results indicate that OR37 receptors may be tuned to distinct fatty aldehydes with a significant degree of ligand specificity. PMID- 22302157 TI - Grey matter volume alterations in CADASIL: a voxel-based morphometry study. AB - CADASIL is a hereditary disease characterized by cerebral subcortical microangiopathy leading to early onset cerebral strokes and progressive severe cognitive impairment. Until now, only few studies have investigated the extent and localization of grey matter (GM) involvement. The purpose of our study was to evaluate GM volume alterations in CADASIL patients compared to healthy subjects. We also looked for correlations between global and regional white matter (WM) lesion load and GM volume alterations. 14 genetically proved CADASIL patients and 12 healthy subjects were enrolled in our study. Brain MRI (1.5 T) was acquired in all subjects. Optimized-voxel based morphometry method was applied for the comparison of brain volumes between CADASIL patients and controls. Global and lobar WM lesion loads were calculated for each patient and used as covariate-of interest for regression analyses with SPM-8. Compared to controls, patients showed GM volume reductions in bilateral temporal lobes (p < 0.05; FDR corrected). Regression analysis in the patient group revealed a correlation between total WM lesion load and temporal GM atrophy (p < 0.05; uncorrected), not between temporal lesion load and GM atrophy. Temporal GM volume reduction was demonstrated in CADASIL patients compared to controls; it was related to WM lesion load involving the whole brain but not to lobar and, specifically, temporal WM lesion load. Complex interactions between sub-cortical and cortical damage should be hypothesized. PMID- 22302158 TI - Subtotal laryngectomy: outcomes of 469 patients and proposal of a comprehensive and simplified classification of surgical procedures. AB - Long-term oncological and functional results from a retrospective study on 469 patients over a 10-year period of subtotal laryngectomies (SL), 399 supracricoid partial laryngectomies (SCL) and 70 supratracheal partial laryngectomies (STL) are presented. The mean follow-up time was 97 months (range 60-165 months). Acute complications, types and rates of late sequelae, functional results, 2-year post operative scores of laryngeal function and quality of life are reported. The observed long-term results were: SCL, 5-year overall and disease-free survival: 95.6, and 90.9%, respectively; 2-year post-operative laryngeal function preservation: 95.7%; STL, 5-year overall and disease-free survival: 80 and 72.9%, respectively; 2-year post-operative laryngeal function preservation: 80%. The performance status scale for laryngeal function preservation showed very high 2 year scores, with no significant differences depending on the type and extent of surgery. The adopted type of function-sparing surgery provided overall and disease-free survival rates that were somewhat better than those reported in studies based on organ-sparing protocols with chemoradiotherapy. The rate of total laryngectomy of completion in this series was 4.4%. A new classification of the current horizontal partial laryngectomies is also proposed, namely "Horizontal Laryngectomy System" (HOLS), based on the extent of surgical removal of laryngeal structures. PMID- 22302159 TI - Vocal characteristics in patients with type 2 diabetes mellitus. AB - The objective of this study is to report the vocal characteristics of patients with type 2 diabetes mellitus in relation to disease duration, glycemic control, and neuropathy. This is a prospective study. The setting is institutional setting. A total of 82 patients were recruited for this study, and a healthy control group matched according to age and gender was recruited. Subjects underwent acoustic analysis and perceptual evaluation using the GRABS classification where G stands for grading, R for roughness, A for asthenia, B for breathiness, and S for straining using a scale of 0-3 where o stands for normal and three for severe deviation from normal. There was no significant difference in any of the acoustic variables between diabetic patients and control. There was no significant difference in the mean score of any of the perceptual evaluation parameters between diabetic patients and control, despite the fact that the mean scores were all higher in the diseased group except for roughness. When looking at subgroups, we see that diabetic patients with poor glycemic control and with neuropathy had significantly higher mean score for the G overall grade of the voice compared to controls with P values of 0.005 and 0.009, respectively. What is also worth noting is that diabetic patients with poor glycemic control had more straining compared to controls, P value 0.043. Patients with type 2 diabetes mellitus and poor glycemic control or neuropathy have a significant difference in the grade of their voice compared to controls. PMID- 22302161 TI - Letter to the editor on: Hanna B. Albert, Eva Hauge, Claus Manniche (2011) Centralization in patients with sciatica: are pain responses to repeated movement and positioning associated with outcome or types of disc lesions? Eur Spine J. doi:10.1007/s00586-011-2018-9. PMID- 22302162 TI - Normal morphology, age-related changes and abnormal findings of the cervical spine. Part II: Magnetic resonance imaging of over 1,200 asymptomatic subjects. AB - PURPOSE: The aim of this study is to establish standard MRI values for the cervical spinal canal, dural tube, and spinal cord, to evaluate age-related changes in healthy subjects, and to assess the prevalence of abnormal findings in asymptomatic subjects. METHODS: The sagittal diameter of the spinal canal and the sagittal diameter and cross-sectional area of the dural tube and spinal cord were measured on MRIs of 1,211 healthy volunteers. These included at least 100 men and 100 women in each decade of life between the third (20s) and eighth (70s). Abnormal findings such as spinal cord compression and signal changes in the spinal cord were recorded. RESULTS: The sagittal diameter of the spinal canal was 11.2 +/- 1.4 mm [mean +/- standard deviation (SD)]/11.1 +/- 1.4 mm (male/female) at the mid-C5 vertebral level, and 9.5 +/- 1.8/9.6 +/- 1.6 mm at the C5/6 disc level. The cross-sectional area of the spinal cord was 78.1 +/- 9.4/74.4 +/- 9.4 mm2 at the mid-C5 level and 70.6 +/- 11.7/68.9 +/- 11.3 mm2 at the C5/6 disc level. Both the sagittal diameter and the axial area of the dural tube and spinal cord tended to decrease with increasing age. This tendency was more marked at the level of the intervertebral discs than at the level of the vertebral bodies, especially at the C5/6 intervertebral disc level. The spinal cord occupation rate in the dural tube at the C5 vertebral body level averaged 58.3 +/- 7.0%. Spinal cord compression was observed in 64 cases (5.3%) and a T2 high-signal change was observed in 28 cases (2.3%). CONCLUSIONS: Using MRI data of 1,211 asymptomatic subjects, the standard values for the cervical spinal canal, dural tube, and spinal cord for healthy members of each sex and each decade of life and the age related changes in these parameters were established. The relatively high prevalence of abnormal MRI findings of the cervical spine in asymptomatic individuals emphasizes the dangers of predicating operative decisions on diagnostic tests without precisely correlating these findings with clinical signs and symptoms. PMID- 22302163 TI - Current challenges in compound-specific stable isotope analysis of environmental organic contaminants. AB - Compound-specific stable-isotope analysis (CSIA) has greatly facilitated assessment of sources and transformation processes of organic pollutants. Multielement isotope analysis is one of the most promising applications of CSIA because it even enables distinction of different transformation pathways. This review introduces the essential features of continuous-flow isotope-ratio mass spectrometry (IRMS) and highlights current challenges in environmental analysis as exemplified for the isotopes of nitrogen, hydrogen, chlorine, and oxygen. Strategies and recent advances to enable isotopic measurements of polar contaminants, for example pesticides or pharmaceuticals, are discussed with special emphasis on possible solutions for analysis of low concentrations of contaminants in environmental matrices. Finally, we discuss different levels of calibration and referencing and point out the urgent need for compound-specific isotope standards for gas chromatography-isotope-ratio mass spectrometry (GC IRMS) of organic pollutants. PMID- 22302164 TI - Mass spectrometry: Fifth meeting of the Spanish Society of Mass Spectrometry (SEEM). PMID- 22302165 TI - Electrochemically synthesized polymers in molecular imprinting for chemical sensing. AB - This critical review describes a class of polymers prepared by electrochemical polymerization that employs the concept of molecular imprinting for chemical sensing. The principal focus is on both conducting and nonconducting polymers prepared by electropolymerization of electroactive functional monomers, such as pristine and derivatized pyrrole, aminophenylboronic acid, thiophene, porphyrin, aniline, phenylenediamine, phenol, and thiophenol. A critical evaluation of the literature on electrosynthesized molecularly imprinted polymers (MIPs) applied as recognition elements of chemical sensors is presented. The aim of this review is to highlight recent achievements in analytical applications of these MIPs, including present strategies of determination of different analytes as well as identification and solutions for problems encountered. PMID- 22302166 TI - Reaction of beta-blockers and beta-agonist pharmaceuticals with aqueous chlorine. Investigation of kinetics and by-products by liquid chromatography quadrupole time-of-flight mass spectrometry. AB - The degradation of two beta-blockers (atenolol and propranolol) and one beta receptor agonist (salbutamol) during water chlorination was investigated by liquid chromatography-mass spectrometry (LC-MS). An accurate-mass quadrupole time of-flight system (QTOF) was used to follow the time course of the pharmaceuticals and also used in the identification of the by-products. The degradation kinetics of these drugs was investigated at different concentrations of chlorine, bromide and sample pH by means of a Box-Behnken experimental design. Depending on these factors, dissipation half-lives varied in the ranges 68-145 h for atenolol, 1.3 33 min for salbutamol and 42-8362 min for propranolol. Normally, an increase in chlorine dosage and pH resulted in faster degradation of these pharmaceuticals. Moreover, the presence of bromide in water samples also resulted in a faster transformation of atenolol at low chlorine doses. The use of an accurate-mass high-resolution LC-QTOF-MS system permitted the identification of a total of 14 by-products. The transformation pathway of beta-blockers/agonists consisted mainly of halogenations, hydroxylations and dealkylations. Also, many of these by products are stable, depending on the chlorination operational parameters employed. PMID- 22302167 TI - Current use of high-resolution mass spectrometry in drug screening relevant to clinical and forensic toxicology and doping control. AB - Clinical and forensic toxicology and doping control deal with hundreds or thousands of drugs that may cause poisoning or are abused, are illicit, or are prohibited in sports. Rapid and reliable screening for all these compounds of different chemical and pharmaceutical nature, preferably in a single analytical method, is a substantial effort for analytical toxicologists. Combined chromatography-mass spectrometry techniques with standardised reference libraries have been most commonly used for the purpose. In the last ten years, the focus has shifted from gas chromatography-mass spectrometry to liquid chromatography mass spectrometry, because of progress in instrument technology and partly because of the polarity and low volatility of many new relevant substances. High resolution mass spectrometry (HRMS), which enables accurate mass measurement at high resolving power, has recently evolved to the stage that is rapidly causing a shift from unit-resolution, quadrupole-dominated instrumentation. The main HRMS techniques today are time-of-flight mass spectrometry and Orbitrap Fourier transform mass spectrometry. Both techniques enable a range of different drug screening strategies that essentially rely on measuring a compound's or a fragment's mass with sufficiently high accuracy that its elemental composition can be determined directly. Accurate mass and isotopic pattern acts as a filter for confirming the identity of a compound or even identification of an unknown. High mass resolution is essential for improving confidence in accurate mass results in the analysis of complex biological samples. This review discusses recent applications of HRMS in analytical toxicology. PMID- 22302168 TI - Protein fractionation and detection for metalloproteomics: challenges and approaches. AB - At least one third of all proteins are thought to require a metal ion co-factor for their function. Recognition of the importance of metals in biological systems and major advances in analytical instrumentation and technology have led to the emergence of the new research area of metalloproteomics in recent years. Despite this progress, the experimental determination of in-vivo metal cofactors has remained challenging, because this requires elucidation of protein interactions with non-covalently bound metal ions. This critical review highlights current methodological approaches, focusing, in particular, on issues relating to the fractionation and separation of the metalloproteome, including recent experience with metalloproteomics for marine cyanobacteria in our laboratory. Metalloproteomics promises to deliver novel insights into fundamental biological processes in the future, but it is clear that further methodological advances are necessary to exploit the full potential of this emerging research area. PMID- 22302169 TI - Microscale separation methods for enzyme kinetics assays. AB - Miniaturization continues to be one of the leading trends in analytical chemistry and one that brings advantages that can be particularly beneficial in biochemical research. Use of a miniaturized scale enables efficient analysis in a short time and requires very small amounts of samples, solvents, and reagents. This can result in a remarkable decrease in costs of enzyme kinetics studies, especially when expensive or rare enzymes and/or substrates are involved. Free zone electrophoresis is without a doubt the most common microscale separation technique for capillary and on-chip enzyme assays. Progress and applications in this field are reviewed frequently whereas other modes of separation, although successfully applied, receive only marginal interest in such publications. This review summarizes applications of less common modes of separation in capillary or chip formats, namely micellar electrokinetic chromatography, liquid chromatography, gel electrophoresis, isoelectric focusing, and isotachophoresis. Because these techniques are based on separation mechanisms different from those of free zone electrophoresis, they can be, and have been, successfully used in cases where zone electrophoresis fails. Advantages and drawbacks of these alternative separation techniques are discussed, as also are the difficulties encountered most often and solutions proposed by different research groups. PMID- 22302170 TI - Polar and non-polar organic binder characterization in Pompeian wall paintings: comparison to a simulated painting mimicking an "a secco" technique. AB - The use of Fourier transform infrared spectromicroscopy and mass spectrometry (MS) allowed us to characterize the composition of polar and non-polar binders present in sporadic wall paint fragments taken from Pompeii's archaeological excavation. The analyses of the polar and non-polar binder components extracted from paint powder layer showed the presence of amino acids, sugars, and fatty acids but the absence of proteinaceous material. These results are consistent with a water tempera painting mixture composed of pigments, flours, gums, and oils and are in agreement with those obtained from a simulated wall paint sample made for mimicking an ancient "a secco" technique. Notably, for the first time, we report the capability to discriminate by tandem MS the presence of free amino acids in the paint layer. PMID- 22302171 TI - Development of a UPLC-ESI-MS/MS method for the determination of larotaxel in beagle dog plasma: application to the pharmacokinetic study. AB - A UPLC-ESI-MS/MS method has been developed and validated for the determination of larotaxel in beagle dog plasma. After addition of the internal standard, plasma samples were extracted by liquid-liquid extraction with methyl tert-butyl ether and separated on a 50*2.1 mm ACQUITY 1.7 MUm C18 column (Waters, USA), with acetonitrile and 5 mM ammonium acetate as mobile phase, within a runtime of 3.0 min. The analytes were detected without interference in Multiple Reaction Monitoring mode with positive electrospray ionization. The linear range was 2.5 5,000 ng/mL. The intra-day and inter-day precisions (relative standard deviation, RSD, %) were within 9.3% and 10.2%, respectively, and the accuracy (relative error, RE, %) was less than 11.5%. The validated method was successfully applied to a pharmacokinetic study of larotaxel in beagle dogs after intravenous administration of larotaxel-loaded lipid microsphere with different doses of 0.4, 0.8, and 1.6 mg/kg. The area under the concentration-time curve and the peak concentration of larotaxel seemed to increase with increasing dose proportionally, suggesting linear pharmacokinetics. PMID- 22302172 TI - A photosynthetic biosensor with enhanced electron transfer generation realized by laser printing technology. AB - One of the limits of current electrochemical biosensors is a lack of methods providing stable and highly efficient junctions between biomaterial and solid state devices. This paper shows how laser-induced forward transfer (LIFT) can enable efficient electron transfer from photosynthetic biomaterial immobilized on screen-printed electrodes (SPE). The ideal pattern, in terms of photocurrent signal of thylakoid droplets giving a stable response signal with a current intensity of approximately 335 +/- 13 nA for a thylakoid mass of 28 +/- 4 ng, was selected. It is shown that the efficiency of energy production of a photosynthetic system can be strongly enhanced by the LIFT process, as demonstrated by use of the technique to construct an efficient and sensitive photosynthesis-based biosensor for detecting herbicides at nanomolar concentrations. PMID- 22302174 TI - Rapid and on-site analysis of illegal drugs on the nano-microscale using a deep ultraviolet-visible reflected optical fiber sensor. AB - A deep ultraviolet-visible (DUV-Vis) reflected optical fiber sensor was developed for use in a simple spectrophotometric detection system to detect the absorption of various illegal drugs at wavelengths between 180 and 800 nm. Quantitative analyses performed using the sensor revealed a high specificity and sensitivity for drug detection at a wavelength of approximately 200 nm. Using a double absorption optical path length, extremely small sample volumes were used (32 to 160 nL), which allowed the use of minimal amounts of samples. A portable spectrophotometric system was established based on our optical fiber sensor for the on-site determination and quantitative analysis of common illegal drugs, such as 3,4-methylenedioxymethamphetamine (MDMA), ketamine hydrochloride, cocaine hydrochloride, diazepam, phenobarbital, and barbital. By analyzing the absorbance spectra, six different drugs were quantified at concentrations that ranged from 0.1 to 1000 MUg mL(-1) (16 pg-0.16 MUg). A novel Matching Algorithm of Spectra Space (MASS) was used to accurately distinguish between each drug in a mixture. As an important supplement to traditional methods, such as mass spectrometry or chromatography, our optical fiber sensor offers rapid and low-cost on-site detection using trace amounts of sample. This rapid and accurate analytical method has wide-ranging applications in forensic science, law enforcement, and medicine. PMID- 22302175 TI - Molybdenum(VI) catalysts obtained from eta3-allyl dicarbonyl precursors: synthesis, characterization and catalytic performance in cyclooctene epoxidation. AB - The oxidative decarbonylation of the eta(3)-allyl dicarbonyl complexes [Mo(eta(3) C(3)H(5))Cl(CO)(2)(L)] (L = 2,2'-bipyridine (bipy) (1), 4,4'-di-tert-butyl-2,2' bipyridine (di-tBu-bipy) (2)) by reaction with aqueous tert-butylhydroperoxide (TBHP) or H(2)O(2) gave the following compounds in good to excellent yields: the oxo-bridged dimers [MoO(2)Cl(L)](2)O (L = bipy (3), di-tBu-bipy (6)) using TBHP(10 equiv.)/CH(3)CN/r.t.; the molybdenum oxide/bipyridine hybrid material {[MoO(3)(bipy)][MoO(3)(H(2)O)]}(n) (4) and the octanuclear complex [Mo(8)O(24)(di tBu-bipy)(4)] (7) using TBHP(50 equiv.)/H(2)O/70 degrees C; the oxodiperoxo complexes MoO(O(2))(2)(L) (L = bipy (5), di-tBu-bipy (8)) using H(2)O(2)(10 equiv.)/CH(3)CN/r.t. The structure of 7.x(solvent) (where solvent = CH(2)Cl(2) and/or diethyl ether) was determined by single crystal X-ray diffraction. Despite possessing the same windmill-type complex as that described previously for 7.10CH(2)Cl(2), the crystal structure of 7.x(solvent) is unique due to differences in the crystal packing. Compounds 1-8 were examined as catalysts or catalyst precursors for the epoxidation of cyclooctene using aqueous TBHP or H(2)O(2) as oxidant at 55 or 70 degrees C. Reactions were performed without co solvent or with the addition of water, ethanol or acetonitrile. Cyclooctene oxide was always the only reaction product. Solids recovered after 24 h reaction at 70 degrees C were identified by FT-IR spectroscopy as the hybrid 4 from (1,3 5)/TBHP, complex 5 from (1,3-5)/H(2)O(2), and complex 8 from (2,6-8)/H(2)O(2). With TBHP as oxidant, the highest epoxide yields (for 24 h reaction at 70 degrees C) were obtained using excess H(2)O as solvent (28-38% for 1,3-5; 87-98% for 2,6-8), while with H(2)O(2) as oxidant, the highest epoxide yields were obtained using CH(3)CN as solvent (54-81% for 3-8). PMID- 22302176 TI - Post injury changes in the properties of mesenchymal stem cells derived from human anterior cruciate ligaments. AB - PURPOSE: The anterior cruciate ligament (ACL) rarely heals spontaneously after rupture. Mesenchymal stem cells (MSCs) contribute to healing in various tissues, therefore, they may also have a key role in healing after ACL rupture. The purpose of this study was to investigate the properties of MSCs in ruptured ACLs. METHODS: Human ACL samples were harvested from patients undergoing primary ACL reconstruction, and samples were classified by the number of days post rupture (phase I<21 days; phase II 21-56 days; phase III 57-139 days phase IV>=140 days). We evaluated the characteristics of MSCs, such as colony-forming capacity, differentiation potential and cell-surface markers. RESULTS: There was a tendency for high colony-forming capacity during phases I and II, which tended to decrease in phase III. Chondrogenic, adipogenic and osteogenic differentiation potential was maintained until phase II but decreased in phase III. Most surface-epitope expression was consistent from phase I to III: positive for CD44, CD73, CD90 and CD105; negative for CD11b, CD19, CD34, CD45 and human leukocyte antigen-D-related (HLA-DR). The presence of these surface markers proved the existence of MSCs in ruptured ACL tissue. CONCLUSIONS: Our results suggest that colony-forming and differentiation potential decrease over time. It is important to consider changes in properties of MSCs and use ACL tissue in the acute phase of rupture when biological manipulation is required. PMID- 22302177 TI - Optimal mechanical environment of the healing bone fracture/osteotomy. AB - The aim of this paper is to review recent experimental and clinical publications on bone biology with respect to the optimal mechanical environment in the healing process of fractures and osteotomies. The basic postulates of bone fracture healing include static bone compression and immobilisation/ fixation for three weeks and intermittent dynamic loading treatment afterwards. The optimal mechanical strain should be in the range of 100-2,000 microstrain, depending on the frequency of the strain application, type of bone and location in the bone, age and hormonal status. Higher frequency of mechanical strain application or larger number of repetition cycles result in increased bone mass at the healing fracture site, but only up to a certain limit, values beyond which no additional benefit is observed. Strain application and transition period from non-load bearing to full load-bearing can be modified by implants allowing dynamisation of compression and generating strains at the fracture healing site in a controlled manner. PMID- 22302178 TI - Incongruity of imaging using fluorescent 2-DG conjugates compared to 18F-FDG in preclinical cancer models. AB - PURPOSE: We compared the use of near-infrared conjugates of 2-deoxyglucose (NIR 2 DG) to 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) for the purposes of imaging tumors, as well as response to therapy. PROCEDURES: Uptake of both 18F-FDG and NIR 2-DG within gastrointestinal stromal tumor xenografts were imaged before and after nilotinib treatment. Confocal microscopy was performed to determine NIR 2 DG distribution in tumors. RESULTS: Treatment with nilotinib resulted in a rapid reduction in 18F-FDG uptake and reduced tumor cell viability which was predictive of long-term antitumor efficacy. In contrast, optical imaging with NIR 2-DG probes was unable to differentiate control from niltonib-treated animals, and microscopic analysis revealed no change in probe distribution as a result of treatment. CONCLUSIONS: These results suggest that conjugation of large bulky fluorophores to 2-DG disrupts the facilitated transport and retention of these probes in cells. Therefore, optical imaging of NIR 2-DG probes cannot substitute for 18F-FDG positron emission tomography imaging as a biomarker of tumor cell viability and metabolism. PMID- 22302179 TI - Brain tissue oxygenation and cerebral perfusion pressure thresholds of ischemia in a standardized pig brain death model. AB - BACKGROUND: Neurointensive care of traumatic brain injury (TBI) patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted protocols. Monitoring brain tissue oxygenation (BtipO2) is of considerable clinical interest, but the exact threshold level of ischemia has been difficult to establish due to the complexity of the clinical situation. The objective of this study was to use the Neurovent-PTO (NV) probe, and to define critical cerebral oxygenation- and CPP threshold levels of cerebral ischemia in a standardized brain death model caused by increasing the ICP in pig. Ischemia was defined by a severe increase of cerebral microdialysis (MD) lactate/pyruvate ratio (L/P ratio > 30). METHODS: BtipO2, L/P ratio, Glucose, Glutamate, Glycerol and CPP were recorded using NV and MD probes during gradual increase of ICP by inflation of an epidural balloon catheter with saline until brain death was achieved. RESULTS: Baseline level of BtipO2 was 22.9 +/- 6.2 mmHg, the L/P ratio 17.7 +/- 6.1 and CPP 73 +/- 17 mmHg. BtipO2 and CPP decreased when intracranial volume was added. The L/P ratio increased above its ischemic levels, (>30)when CPP decreased below 30 mmHg and BtipO2 to <10 mmHg. CONCLUSIONS: A severe increase of ICP leading to CPP below 30 mmHg and BtipO2 below 10 mmHg is associated with an increase of the L/P ratio, thus seems to be critical thresholds for cerebral ischemia under these conditions. PMID- 22302180 TI - Neural Regulation of the Stress Response: The Many Faces of Feedback. AB - The mammalian stress response is an integrated physiological and psychological reaction to real or perceived adversity. Glucocorticoids (GCs) are an important component of this response, acting to redistribute energy resources to both optimize survival in the face of challenge and restore homeostasis after the immediate threat has subsided. Release of GCs is mediated by the hypothalamo pituitary-adrenocortical (HPA) axis, driven by a neural signal originating in the paraventricular nucleus (PVN). Stress levels of GCs bind to glucocorticoid receptors (GRs) in multiple body compartments, including brain, and consequently have wide-reaching actions. For this reason, GCs serve a vital function in feedback inhibition of their own secretion. Fast, non-genomic feedback inhibition of the HPA axis is mediated at least in part by GC signaling in the PVN, acting by a cannabinoid-dependent mechanism to rapidly reduce both neural activity and GC release. Delayed feedback termination of the HPA axis response is mediated by forebrain GRs, presumably by genomic mechanisms. GCs also act in the brainstem to attenuate neuropeptidergic excitatory input to the PVN via acceleration of mRNA degradation, providing a mechanism to attenuate future responses to stressors. Thus, rather than having a single defined feedback switch, GCs work through multiple neurocircuits and signaling mechanisms to coordinate HPA axis activity to suit the overall needs of multiple body systems. PMID- 22302181 TI - Quantitative analysis of perfusion studies: strengths and pitfalls. AB - Tools for automated quantification of myocardial perfusion are available to nuclear cardiology practitioners and researchers. These methods have demonstrated superior reproducibility with comparable diagnostic and prognostic performance, when compared with segmental visual scoring by expert observers. A particularly useful application of the quantitative analysis can be in the detection of subtle changes or in precise determination of ischemia. Some challenges remain in the routine application of perfusion quantification. Multiple quantitative parameters may need to be reconciled by the expert reader for the final diagnosis. Computer analysis may be sensitive to imaging artifacts, resulting in false positive scans. Perfusion quantification may require site specific normal limits and some degree of manual interaction. New software improvements have been proposed to address some of these challenges. PMID- 22302183 TI - Investigation on circular asymmetry of geographical distribution in cancer mortality of Hiroshima atomic bomb survivors based on risk maps: analysis of spatial survival data. AB - While there is a considerable number of studies on the relationship between the risk of disease or death and direct exposure from the atomic bomb in Hiroshima, the risk for indirect exposure caused by residual radioactivity has not yet been fully evaluated. One of the reasons is that risk assessments have utilized estimated radiation doses, but that it is difficult to estimate indirect exposure. To evaluate risks for other causes, including indirect radiation exposure, as well as direct exposure, a statistical method is described here that evaluates risk with respect to individual location at the time of atomic bomb exposure instead of radiation dose. In addition, it is also considered to split the risks into separate risks due to direct exposure and other causes using radiation dose. The proposed method is applied to a cohort study of Hiroshima atomic bomb survivors. The resultant contour map suggests that the region west to the hypocenter has a higher risk compared to other areas. This in turn suggests that there exists an impact on risk that cannot be explained by direct exposure. PMID- 22302182 TI - Effect of caffeine on adenosine-induced reversible perfusion defects assessed by automated analysis. AB - OBJECTIVES: This prospective study investigated the effects of caffeine ingestion on the extent of adenosine-induced perfusion abnormalities during myocardial perfusion imaging (MPI). METHODS: Thirty patients with inducible perfusion abnormalities on standard (caffeineabstinent) adenosine MPI underwent repeat testing with supplementary coffee intake. Baseline and test MPIs were assessed for stress percent defect, rest percent defect, and percent defect reversibility. Plasma levels of caffeine and metabolites were assessed on both occasions and correlated with MPI findings. RESULTS: Despite significant increases in caffeine [mean difference 3,106 MUg/L (95% CI 2,460 to 3,752 MUg/L; P < .001)] and metabolite concentrations over a wide range, there was no statistically significant change in stress percent defect and percent defect reversibility between the baseline and test scans. The increase in caffeine concentration between the baseline and the test phases did not affect percent defect reversibility (average change -0.003 for every 100 MUg/L increase; 95% CI -0.17 to 0.16; P = .97). CONCLUSION: There was no significant relationship between the extent of adenosine-induced coronary flow heterogeneity and the serum concentration of caffeine or its principal metabolites. Hence, the stringent requirements for prolonged abstinence from caffeine before adenosine MPI - based on limited studies - appear ill-founded. PMID- 22302184 TI - Radiation effects in generic populations inhabiting a limiting environment. AB - A generic population model is formulated for radiation risk assessment of natural biota. The model demonstrates that effects of radiation on the population survival do not follow directly the effects on individual organisms. Dose rates resulting in population extinction can be analytically calculated. Besides individual radiosensitivity, two key parameters were found to determine the survival potential of a population under chronic radiation stress: the ratio "biomass losses/biomass synthesis," and the lump amount of limiting resource in the environment. A benchmark scenario "Population response to chronic irradiation" developed within the IAEA Programme EMRAS II was calculated for generic populations of mice, hare/rabbit, wolf/wild dog, and deer/goat chronically exposed to different levels of ionizing radiation. In the conditions of the benchmark scenario, model populations survived normally (>90% of the control value) at dose rates below the following levels: 3 mGy day(-1) for wolf/wild dog; 10 mGy day(-1) for deer/goat; 14 mGy day(-1) for hare/rabbit; and 20 mGy day(-1) for mice. The model predictions showed a relatively high survival potential of short-lived and productive species such as mice. At the same time, populations of long-lived animals with slow and radiosensitive reproduction such as wolf/wild dog were candidates to extinction at chronic exposures above 5 mGy day(-1). Recovery of short-lived and productive species took a much shorter time compared with long-lived and slow reproductive species. PMID- 22302185 TI - The socio-political situation of Avicenna's time and his spiritual messages: on the occasion of 1031 st birth anniversary of Avicenna (23 August 980). AB - In the fourth century A.H. (tenth century AD) many thinkers, philosophers, jurisprudents, poets, and authors were present in different scientific, literary and health fields in ancient Iran and Islamic world that by their hard attempts the sciences and literature were safe from incidents and resulted in growth, development and innovation of Islamic sciences. Meanwhile, Avicenna was superior to all others and the most famous scientist. He was a great human that by attempting hard, perseverance, stability, patience, and believing in God could complete supreme scientific ranks and compiled encyclopedia of Canon of Medicine and besides gathering many written important issues that most of them were confiscated at libraries of kings. He added medical experiences of ancient Iran and especially Jondishapour University and also his personal experiences and finally Canon of Medicine by benefiting from monotheistic style and science based on faith was written. He has written a book that is regarded as root and basics of modern medicine and by completing it some infrastructure health viewpoints and common medicine were created. It is a kind of book that in spite of scientific advances and production of modern research tools many of its contents are replaced with modern methods of medicine and health, but still many of its health basic messages, research orientation and monotheism with great dynamic mode is considerable at world's medical references. The aim of this study is evaluate the political situation of Avicenna's time and a review of his Godly writings. This is a library study by using electronic version of Canon of Medicine and other related resources. Findings, include writing style of monotheistic literature, and freeing from nihilism and affiliating diseases to Satan, jinn and such issues. It is necessary that our students within course of Iranian and Islamic culture and civilization to be more familiar with monotheistic thoughts and activities of scientists like Avicenna. PMID- 22302186 TI - Efficient synthesis of 2,5-disubstituted tetrazoles via the Cu2O-catalyzed aerobic oxidative direct cross-coupling of N-H free tetrazoles with boronic acids. AB - We present a new protocol that allows for the synthesis of 2,5-disubstituted tetrazoles via the direct coupling of N-H free tetrazoles and low toxic boronic acids in the presence of only a catalytic amount of Cu(2)O (5 mol%) as catalyst and 1 atm of environmentally benign O(2) as oxidant, without the need for other additives. This method represents a simple, green, and atom-efficient synthesis of 2,5-disubstituted tetrazoles. PMID- 22302187 TI - Trace gas detection of molecular hydrogen H(2) by photoacoustic stimulated Raman spectroscopy (PARS). AB - Photoacoustic stimulated Raman spectroscopy (PARS) has been used for sensitive and selective trace gas detection of molecular hydrogen under ambient conditions. In one experiment, 532 nm output of a seeded pulsed Nd:YAG laser is employed as Raman pump source and a Raman shifter filled with gaseous H(2) to obtain Stokes shifted radiation at 683 nm, suitable to stimulate H(2) Raman detection in a photoacoustic cell. A noise equivalent detection limit of 40 ppm by volume H(2) in 1 atm N(2) is obtained (14 mJ at 532 nm, 18 mJ at 683 nm, 10 Hz repetition rate, 58 s measurement time). Another experiment employs a dye laser for stimulating Raman radiation between 681-684 nm, allowing tuneable PARS. A Gaussian spectral fitting procedure has been applied giving a noise equivalent detection limit of 4.6 ppm by volume H(2) in 1 atm N(2) (35 mJ pulse energy at 532 nm, 45 mJ at 681-684 nm, 10 Hz repetition rate, 256 s measurement time). Spectroscopic detection offers the advantage of high selectivity along with the ability to obtain temperature and dynamic information from the rotational population and a line shape analysis, and also allows the discrimination between ortho- and para-H(2). PMID- 22302188 TI - Comparing the eyes depicted in Japanese portraits of beautiful women: the Meiji and modern periods. AB - BACKGROUND: The women portrayed in the bijin-ga of the past, particularly those from the Meiji Period (1868-1912), tended not to show much resemblance to those of women portrayed in the more modern bijin-ga (from after World War II), and such an observation came across as a possible indication that Japanese standards of beauty have changed over the two eras. To examine whether the apparent discrepancy can be interpreted as an actual change in the standards or not, a study was designed with the aim of assigning numeric values to several aspects of the eyes and testing for the presence of a statistically significant difference in each of the aspects between the Meiji bijin-ga and the modern bijin-ga. METHODS: For this study, 29 Meiji bijin-ga and 36 modern bijin-ga were selected. The eye was chosen as the subject of comparison, and five aspects were categorized and measured: (1) presence or absence of a double fold, (2) eye width, (3) eye height, (4) eyebrow-to-upper lid distance, and (D) corneal diameter. The eye width, the eye height, and the eyebrow-to-upper lid distance were divided by the corneal diameter to derive standardized grounds for comparison. RESULTS: The difference in double-fold frequencies between the Meiji bijin-ga (24%) and the modern bijin-ga (36%) was not found to be statistically significant (p=0.298). There was no difference in the eye width-to-corneal diameter ratio between the Meiji bijin-ga (mean 2.57+/-0.6) and the modern bijin ga (mean 2.61+/-0.85) (p=0.86). The eye height-to-corneal diameter ratio derived from the Meiji bijin-ga (mean 0.62+/-0.15) was significantly smaller than that derived from the modern bijin-ga (mean 0.82+/-0.18) (p=0.000). The eyebrow to upper lid distance-to-corneal diameter ratio derived from the Meiji bijin-ga (mean 2.21+/-0.83) was significantly greater than that derived from the modern bijin-ga (mean 1.36+/-0.78) (p=0.000). CONCLUSIONS: The results of the study support the notion that Westernization contributed to bringing about changes in the Japanese standards of beautiful eyes in the context of bijin-ga. However, the fact that the changeover has not occurred in all the categories in question does not indicate that the Occidental characteristics came to be emulated in their entirety. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at http://www.springer.com/00266. PMID- 22302190 TI - 31P-magnetic resonance spectroscopy (31P-MRS) detects early changes in kidney high-energy phosphate metabolism during a 6-month Valsartan treatment in diabetic and non-diabetic kidney-transplanted patients. AB - (31)P-magnetic resonance spectroscopy ((31)P-MRS) is a non-invasive tool to study high-energy phosphate (HEP) metabolism. We evaluate whether 31P-MRS can detect early changes in kidney HEP metabolism during a 6-month trial with Valsartan. Twenty consecutive stable and normotensive kidney-transplanted patients were enrolled. Nine of them received short-term low-dose Valsartan treatment (80 mg/day) for 6 months, while 11 controls received no medication. Kidney HEP metabolism was evaluated both at baseline and after treatment by (31)P-MRS with a 1.5 T system (Gyroscan Intera Master 1.5 MR System; Philips Medical Systems, Best, The Netherlands). Valsartan-treated patients (n = 9) showed a significant increase in beta-ATP/Pi ratio, a marker of kidney HEP metabolism (baseline = 1.03 +/- 0.08 vs. 6 months = 1.26 +/- 0.07, p = 0.03). In contrast, the b-ATP/Pi ratio in the control group (n = 11) did not change (baseline = 0.85 +/- 0.10 vs. 6 months = 0.89 +/- 0.08, ns). The improvement in the beta-ATP/Pi ratio was not associated with a reduction in arterial blood pressure or in urinary albumin excretion. Kidney-localized (31)P-MRS can detect early changes in kidney HEP metabolism during a short-term low-dose Valsartan treatment in stable normotensive kidney-transplanted patients. PMID- 22302191 TI - A replacement for islet equivalents with improved reliability and validity. AB - Islet equivalent (IE), the standard estimate of isolated islet volume, is an essential measure to determine the amount of transplanted islet tissue in the clinic and is used in research laboratories to normalize results, yet it is based on the false assumption that all islets are spherical. Here, we developed and tested a new easy-to-use method to quantify islet volume with greater accuracy. Isolated rat islets were dissociated into single cells, and the total cell number per islet was determined by using computer-assisted cytometry. Based on the cell number per islet, we created a regression model to convert islet diameter to cell number with a high R2 value (0.8) and good validity and reliability with the same model applicable to young and old rats and males or females. Conventional IE measurements overestimated the tissue volume of islets. To compare results obtained using IE or our new method, we compared Glut2 protein levels determined by Western Blot and proinsulin content via ELISA between small (diameter<=100 MUm) and large (diameter>=200 MUm) islets. When normalized by IE, large islets showed significantly lower Glut2 level and proinsulin content. However, when normalized by cell number, large and small islets had no difference in Glut2 levels, but large islets contained more proinsulin. In conclusion, normalizing islet volume by IE overestimated the tissue volume, which may lead to erroneous results. Normalizing by cell number is a more accurate method to quantify tissue amounts used in islet transplantation and research. PMID- 22302192 TI - Life without nephrin: it's for the birds. PMID- 22302193 TI - Sonic hedgehog signaling mediates epithelial-mesenchymal communication and promotes renal fibrosis. AB - Sonic hedgehog (Shh) signaling is a developmental signal cascade that plays an essential role in regulating embryogenesis and tissue homeostasis. Here, we investigated the potential role of Shh signaling in renal interstitial fibrogenesis. Ureteral obstruction induced Shh, predominantly in the renal tubular epithelium of the fibrotic kidneys. Using Gli1(lacZ) knock-in mice, we identified renal interstitial fibroblasts as Shh-responding cells. In cultured renal fibroblasts, recombinant Shh protein activated Gli1 and induced alpha smooth muscle actin (alpha-SMA), desmin, fibronectin, and collagen I expression, suggesting that Shh signaling promotes myofibroblast activation and matrix production. Blockade of Shh signaling with cyclopamine abolished the Shh-mediated induction of Gli1, Snail1, alpha-SMA, fibronectin, and collagen I. In vivo, the kidneys of Gli1-deficient mice were protected against the development of interstitial fibrosis after obstructive injury. In wild-type mice, cyclopamine did not affect renal Shh expression but did inhibit induction of Gli1, Snail1, and alpha-SMA. In addition, cyclopamine reduced matrix expression and mitigated fibrotic lesions. These results suggest that tubule-derived Shh mediates epithelial-mesenchymal communication by targeting interstitial fibroblasts after kidney injury. We conclude that Shh/Gli1 signaling plays a critical role in promoting fibroblast activation, production of extracellular matrix, and development of renal interstitial fibrosis. PMID- 22302194 TI - Global trends in rates of peritoneal dialysis. AB - Although there is a perception that the use of peritoneal dialysis is declining worldwide, compilations of global data are unavailable to test this hypothesis. We assessed longitudinal trends in the use of peritoneal dialysis from 1997 to 2008 in 130 countries. The preferred data sources were renal registries, followed by nephrology societies, health ministries, academic centers, national experts, and industry affiliates. In 2008, there were approximately 196,000 peritoneal dialysis patients worldwide, representing 11% of the dialysis population. In total, 59% were treated in developing countries and 41% in developed countries. Over 12 years, the number of peritoneal dialysis patients increased in developing countries by 24.9 patients per million population and in developed countries by 21.8 per million population. The proportion of all dialysis patients treated with peritoneal dialysis did not change in developing countries but significantly declined in developed countries by 5.3%. The use of automated peritoneal dialysis increased by 14.5% in developing countries and by 30.3% in developed countries. In summary, the number of patients treated with peritoneal dialysis rose worldwide from 1997 to 2008, with a 2.5-fold increase in the prevalence of peritoneal dialysis patients in developing countries. The proportion of all dialysis patients treated with this modality continues to decline in developed countries. PMID- 22302195 TI - Injection of amniotic fluid stem cells delays progression of renal fibrosis. AB - Injection of amniotic fluid stem cells ameliorates the acute phase of acute tubular necrosis in animals by promoting proliferation of injured tubular cells and decreasing apoptosis, but whether these stem cells could be of benefit in CKD is unknown. Here, we used a mouse model of Alport syndrome, Col4a5(-/-) mice, to determine whether amniotic fluid stem cells could modify the course of progressive renal fibrosis. Intracardiac administration of amniotic fluid stem cells before the onset of proteinuria delayed interstitial fibrosis and progression of glomerular sclerosis, prolonged animal survival, and ameliorated the decline in kidney function. Treated animals exhibited decreased recruitment and activation of M1-type macrophages and a higher proportion of M2-type macrophages, which promote tissue remodeling. Amniotic fluid stem cells did not differentiate into podocyte-like cells and did not stimulate production of the collagen IVa5 needed for normal formation and function of the glomerular basement membrane. Instead, the mechanism of renal protection was probably the paracrine/endocrine modulation of both profibrotic cytokine expression and recruitment of macrophages to the interstitial space. Furthermore, injected mice retained a normal number of podocytes and had better integrity of the glomerular basement membrane compared with untreated Col4a5(-/-) mice. Inhibition of the renin-angiotensin system by amniotic fluid stem cells may contribute to these beneficial effects. In conclusion, treatment with amniotic fluid stem cells may be beneficial in kidney diseases characterized by progressive renal fibrosis. PMID- 22302197 TI - Non-HLA antibodies to immunogenic epitopes predict the evolution of chronic renal allograft injury. AB - Chronic allograft injury (CAI) results from a humoral response to mismatches in immunogenic epitopes between the donor and recipient. Although alloantibodies against HLA antigens contribute to the pathogenesis of CAI, alloantibodies against non-HLA antigens likely contribute as well. Here, we used high-density protein arrays to identify non-HLA antibodies in CAI and subsequently validated a subset in a cohort of 172 serum samples collected serially post-transplantation. There were 38 de novo non-HLA antibodies that significantly associated with the development of CAI (P<0.01) on protocol post-transplant biopsies, with enrichment of their corresponding antigens in the renal cortex. Baseline levels of preformed antibodies to MIG (also called CXCL9), ITAC (also called CXCL11), IFN-gamma, and glial-derived neurotrophic factor positively correlated with histologic injury at 24 months. Measuring levels of these four antibodies could help clinicians predict the development of CAI with >80% sensitivity and 100% specificity. In conclusion, pretransplant serum levels of a defined panel of alloantibodies targeting non-HLA immunogenic antigens associate with histologic CAI in the post transplant period. Validation in a larger, prospective transplant cohort may lead to a noninvasive method to predict and monitor for CAI. PMID- 22302196 TI - The long and short of microRNAs in the kidney. AB - MicroRNAs (miRNAs) are a group of small, noncoding RNAs that act as novel regulators of gene expression through the post-transcriptional repression of their target mRNAs. miRNAs have been implicated in diverse biologic processes, and it is estimated that up to half of all transcripts are regulated by miRNAs. Recent studies also demonstrate a critical role for miRNAs in renal development, physiology, and pathophysiology. Understanding the function of miRNAs in the kidney may lead to innovative approaches to renal disease. PMID- 22302198 TI - Green oncology: cultivating sustainability in medical oncology. AB - INTRODUCTION: Green oncology is a new conceptual and operational paradigm of oncology, which compared to the traditional biomedical model focused on the interest of a single patient and on its exclusive relationship with the doctor, represents a complex evolutionary step towards clinical activities that have to be eco-responsible of the potential current and future impact on the human, professional, structural, technological, and organizational environment, where they arise, as well as on the biosphere. DEFINITION: Green oncology works through ethical and managerial choices that incorporate, besides the traditional criteria of efficiency and effectiveness, the criterion of cultural, economic, environmental, and social sustainability as they are fair, livable, and possible to be realized. PMID- 22302199 TI - Lanthanide complexes assembled from two flexible amide-type tripodal ligands: terminal groups effect on photoluminescence behavior. AB - To explore the effect of terminal groups of tripodal ligands on the photoluminescence behaviors of the complexes, lanthanide (Eu(III), Tb(III)) nitrate complexes with two flexible amide-type tripodal ligands, 2,2',2'' nitrilotris-(N-phenylmethyl)-acetamide (L(I)) and 2,2',2''-nitrilotris-(N naphthalenemethyl)-acetamide (L(II)) were synthesized and characterized. The general formulas of the complexes are [EuL(I)(2)(C(3)H(6)O)].(NO(3))(3).(HCCl(3)).(H(2)O)(4) (1), TbL(I)(2)(NO(3))(3).2H(2)O (2), EuL(II)(NO(3))(3) (3), and TbL(II)(NO(3))(3) (4). Among them, 1, 3, and 4 were characterized by single-crystal X-ray diffraction. Complex 1 demonstrates a 1 : 2 (ML(2)) capsule type stoichiometry, and the complexes 3 and 4 confirm 1 : 1 (ML) type coordination structures. What is more, the triplet energy levels of L(I) and L(II) are 24,331 and 19,802 cm(-1), which were determined from the phosphorescence spectra of the Gd(III) complexes. Ligand modification by changing the terminal groups alters their triplet energy, and results in a different sensitizing ability towards lanthanide ions. The density functional theory (DFT) calculations of energy levels including HOMO, LUMO, singlet, and triplet energies tuned by the different terminal groups are also discussed in detail, and the trends are almost consistent with the experimental conclusions. PMID- 22302200 TI - A case--control study of craniofacial features of children with obstructed sleep apnea. AB - OBJECTIVE: This study aims to analyze differences in the skeletal, dental, and soft tissue components of craniofacial structure predisposing to the pediatric obstructive sleep apnea, by a comparison of the cephalograms between children with obstructive sleep apnea (OSA) and controls. MATERIALS AND METHODS: The study enrolled a total of 30 children who were composed of the following two groups: 15 OSA patients and 15 controls. The two groups were strictly matched by age and sex. Lateral head radiographs were obtained and then cephalometric measurements were compared between the two. Fifty-six measurements were determined to study various skeletal, soft tissue, and airway structure. RESULTS: Marked differences were demonstrated in terms of SNB, PG-NB, lower facial height, H-C3Me, and adenoid (A) and tonsil (T/P). The SNB angle (75.82 +/- 4.30) in case group was smaller than in the control (78.71 +/- 2.61; p = 0.035), the PG/NB value in case group (1.32 +/- 0.84 mm) was higher than that in the control (0.62 +/- 0.60 mm; p = 0.015). The anterior lower facial height was 65.12 +/- 5.91 mm in case group (p = 0.048), while the anterior lower facial height in control was 61.51 +/- 3.22 mm. The position of hyoid was lower in case group (5.30 +/- 3.67 mm) compared with the control one (2.64 +/- 2.58 mm; p = 0.029). Furthermore, the patients with OSA had larger As and T/Ps than the controls. CONCLUSIONS: The case group differed from the control group in the length of mandible, anterior lower facial height, position of hyoid and the chin, and the size of the As and T/Ps. PMID- 22302201 TI - Obstructive pressure peak: a new method for differentiation of obstructive and central apneas under auto-CPAP therapy. AB - PURPOSE: Auto-CPAP devices (APAP) are controlled, e.g.,by the respiratory flow and pressure to adjust the treatment pressure to the variable obstruction in sleep apnea syndromes.By obstruction of the upper airway during inspiration,a pressure difference between the lower airways and the mask can be measured. In case of an opening of the pharynx at the end of the obstruction, the pressure decreases immediately. This brief negative pressure, the so-called obstructive pressure peak (OPP) can be used to identify obstruction or open airways with the algorithm of an APAP device. Useless pressure increases, e.g., after central apneas without obstruction may be avoided. We therefore investigated the association of the OPP signal with respiratory events during APAP therapy. METHODS: In this pilot study, 13 patients with obstructive sleep apnea syndrome were evaluated. Attended automatic CPAP titration (SOMNO balance, Fa Weinmann Hamburg/Germany)was performed. The OPP signal was recorded synchronous lyin parallel with the polysomnographic data. If the OPP signal was within a time range of +/- 5 s of the resumption of normal breathing, it was assigned to the event. RESULTS: A total of 480 sleep-related breathing disorders events were studied. The most common were the mixed apneas associated with more than 90% of all cases with an OPP signal, followed by obstructive sleep apneas (66.7%)and central apneas (38%). The difference in OPP frequency distribution between central apneas and obstructive apneas was significant with p<0.001. CONCLUSIONS: The analysis of the pressure characteristics of APAP treatment with the registration of OPP allows a further differentiation in obstructed and not obstructed upper airways. PMID- 22302202 TI - Characterization of HIV-associated Hodgkin's lymphoma in HIV-infected patients: a single-center experience. AB - INTRODUCTION: Although the incidence and prevalence of AIDS-defining malignancies has decreased in the era of highly active antiretroviral therapy (HAART), the incidence and prevalence of Hodgkin's lymphoma (HL) in the HIV-infected population continues to rise. Compared with the general population, HIV-infected patients exhibit a 5-10-fold increased risk for developing HL. METHODS: A retrospective review of charts and electronic records from 2000-2010 at the HIV outpatient clinic (HOP)-Louisiana State University in New Orleans was conducted, and pathologically confirmed cases of HIV-HL were identified within this cohort. RESULTS: We found a prevalence of 6.3 cases per 1,000 patients per year of HIV-HL over a period of 10 years in our HIV outpatient clinic. The mean absolute CD4 count before treatment was 284 cells/mm(3) and after treatment was 194 cells/mm(3). The average time from the diagnosis of HIV infection to the diagnosis of HIV-HL was 7.6 years. The most common histopathologic type was mixed cellularity followed by lymphocytic predominance. The majority of patients had 6 cycles delivered. In terms of HL staging 87% presented with advanced stages (III B or IV). To the best of our knowledge 5 out of the 14 patients remain alive. CONCLUSIONS: Patients in our cohort were older than most patients identified in other cohorts. All of our patients had coexisting chronic illnesses associated with inflammation, as well as detectable HIV viral loads and CD4 count >200, suggesting a role for both HIV- and non-HIV-associated inflammation in HIV-HL pathogenesis in this population. The role of HIV virus and other oncogenic viruses (EBV, HPV, and others) in the pathogenesis of Hodgkin's lymphoma in this group of patients needs to be elucidated. PMID- 22302203 TI - Restoration of labral anatomy and biomechanics after superior labral anterior posterior repair: comparison of mattress versus simple technique. AB - BACKGROUND: Both simple and mattress repair techniques have been utilized with success for type II superior labral anterior-posterior (SLAP) lesions; however, direct anatomic and biomechanical comparisons of these techniques have yet to be clearly demonstrated. HYPOTHESIS: For type II SLAP lesions, the mattress suture repair technique will result in greater labral height and better position on the glenoid face and exhibit stronger biomechanical characteristics, when cyclically loaded and loaded to failure through the biceps, compared with the simple suture repair technique. STUDY DESIGN: Controlled laboratory study. METHODS: Six matched pairs of cadaveric shoulders were dissected, and a clock face was created on the glenoid from 9 o'clock (posterior) to 3 o'clock (anterior). For the intact specimen, labral height and labral distance from the glenoid edge were measured using a MicroScribe. A SLAP lesion was then created from 10 o'clock to 2 o'clock. Lesions were repaired with two 3.0-mm BioSuture-Tak anchors placed at 11 o'clock and 1 o'clock. For each pair, a mattress repair was used for one shoulder, and a simple repair was used for the contralateral shoulder. After repair, labral height and labral distance from the glenoid edge were again measured. The specimens were then cyclically loaded and loaded to failure through the biceps using an Instron machine. A paired t test was used for statistical analysis. RESULTS: After mattress repair, a significant increase in labral height occurred compared with intact from 2.5 +/- 0.3 mm to 4.3 +/- 0.3 mm at 11 o'clock (P = .013), 2.7 +/- 0.5 mm to 4.2 +/- 0.7 mm at 12:30 o'clock (P = .007), 3.1 +/- 0.5 mm to 4.2 +/- 0.7 mm at 1 o'clock (P = .006), and 2.8 +/- 0.7 mm to 3.7 +/- 0.8 mm at 1:30 o'clock (P = .037). There was no significant difference in labral height between the intact condition and after simple repair at any clock face position. Labral height was significantly increased in the mattress repairs compared with simple repairs at 11 o'clock (mean difference, 2.0 mm; P = .008) and 12:30 o'clock (mean difference, 1.3 mm; P = .044). Labral distance from the glenoid edge was not significantly different between techniques. No difference was observed between the mattress and simple repair techniques for all biomechanical parameters, except the simple technique had a higher load and energy absorbed at 2-mm displacement. CONCLUSION: The mattress technique created a greater labral height while maintaining similar biomechanical characteristics compared with the simple repair, with the exception of load and energy absorbed at 2-mm displacement, which was increased for the simple technique. CLINICAL RELEVANCE: Mattress repair for type II SLAP lesions creates a higher labral bumper compared with simple repairs, while both techniques resulted in similar biomechanical characteristics. PMID- 22302204 TI - Accuracy analysis of a novel electromagnetic navigation procedure versus a standard fluoroscopic method for retrograde drilling of osteochondritis dissecans lesions of the knee. AB - BACKGROUND: Retrograde drilling for osteochondritis dissecans (OCD) remains a challenging operation. PURPOSE: A novel radiation-free electromagnetic navigation system (ENS)-based method was developed and its feasibility and accuracy for retrograde drilling procedures evaluated and compared with the standard freehand fluoroscopic method in an experimental setting. STUDY DESIGN: Controlled laboratory study. METHODS: A controlled laboratory study with 16 standard freehand fluoroscopically and 16 electromagnetically guided retrograde drilling procedures was performed on 8 cadaveric human knees. Four artificial cartilage lesions (2 on each condyle) were set per knee. Drilling accuracy was determined by final distance from the tip of the drill bit to the tip of the probe hook (D1) and distance between the tip of the drill and the marked lesion on the cartilage surface (D2). Intraoperative fluoroscopy exposure times were documented, as were directional readjustments or complete restarts. All procedures were timed using a stopwatch. RESULTS: Successful retrograde drilling was accomplished in all 16 cases using the novel ENS-based method and in 11 cases using the standard fluoroscopic technique. The overall mean time for the fluoroscopy-guided procedures was 10 minutes 55 seconds +/- 3 minutes 19 seconds and for the ENS method was 5 minutes 34 seconds +/- 38 seconds, providing a mean time benefit of 5 minutes 35 seconds (P < .001). Mean D1 was 3.8 +/- 1.6 mm for the standard and 2.3 +/- 0.6 mm using the ENS technique (P = .021), and mean D2 was 2.5 +/- 1.3 mm for the standard and 0.9 +/- 0.7 mm for the ENS-based method (P < .001). CONCLUSION: Compared with the standard fluoroscopic technique, the novel ENS based method used in this study showed superior accuracy, required less time, and utilized no radiation. CLINICAL RELEVANCE: The novel method improves a standard operating procedure in terms of accuracy, operation time for the retrograde drilling procedure, and radiation exposure. PMID- 22302205 TI - Running activity after hip resurfacing arthroplasty: a prospective study. AB - BACKGROUND: The ability to return to sports activities (especially running) after hip resurfacing arthroplasty seems to be very important for young and active patients who have developed osteoarthritis. PURPOSE: To assess the quality of return to sports after hip resurfacing arthroplasty by examining the time spent running, weekly mileage, and the possibility of returning to competition in a series of patients. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A prospective, consecutive series of 202 patients (215 hip resurfacings) was assessed to evaluate the possible resumption of running activity (time spent, weekly mileage, return to competition). Of this initial cohort, 40 patients (43 resurfacings, 21%) practiced running preoperatively. Mean age at hip resurfacing arthroplasty was 50.7 years (range, 31-61 years). No patients underwent revision surgery. A questionnaire was administered to assess the number, type, and level of sports activities. Among patients who practiced running, we determined, preoperatively and at last follow-up, their weekly mileage and whether they were competitors. RESULTS: At last follow-up, 33 of 40 patients (36/43 hips) still practiced running (P = .74), with 91.6% of them resuming running. Mean average recovery time before running at a level assessed as good by patients was 16.4 weeks (range, 5-36 weeks). The number of patients running more than 4 hours per week increased from 18 to 23. Similarly, the time devoted to running at last follow-up remained high (mean, 3.1 hours per week) with no statistically significant difference from the preoperative period (P = .54). Moreover, patients were still engaged in competition without statistical difference between the 2 periods (P = .82). CONCLUSION: Running is possible after hip resurfacing, and runners can even return to some level of competition, but this short follow-up series of hip resurfacing in athletes should be interpreted with caution regarding implant survival. PMID- 22302206 TI - The relationship between femoral tunnels created by the transtibial, anteromedial portal, and outside-in techniques and the anterior cruciate ligament footprint. AB - BACKGROUND: Tunnels created for reconstruction of a torn anterior cruciate ligament (ACL) are critical determinants of joint stability and clinical outcomes. There is limited objective evidence on the ability of transtibial (TT), anteromedial (AM) portal, and outside-in (OI) operative techniques in creating anatomic tunnels. HYPOTHESIS: (1) Tibial tunnel-independent techniques can create tunnels more accurately at the anatomic ACL footprint center than the TT technique, and (2) femoral tunnel exit location of the OI and TT techniques on the lateral cortex will be significantly further away from the lateral epicondyle than the femoral tunnel exit location of the AM portal technique. STUDY DESIGN: Controlled laboratory study. METHODS: Eight cadaveric knee specimens with a mean age of 56 years were used in this study. A digitizing system was used to record points along the outlines of the ACL insertion area and apertures of tunnels created by the TT, AM portal, and OI techniques. The following parameters were measured from the digitized points: (1) amount of ACL, anteromedial bundle, and posterolateral bundle coverage by the tunnels; (2) relationship between the centers of the ACL and the tunnels; and (3) distance between the center of the femoral tunnel exit and the lateral epicondyle. All the recorded parameters were analyzed in 3-dimensional solid modeling software. RESULTS: The percentage of ACL footprint coverage achieved by all 3 surgical techniques was not significantly different from one another. However, larger femoral posterolateral bundle coverage was observed in tunnels created by the AM portal and OI techniques than in the TT tunnel. In terms of anteromedial bundle coverage, no significant differences were observed between the 3 techniques. On average, 27.1% +/- 17.4% of the TT tunnel was outside the ACL footprint. This was significantly larger compared with 13.6% +/- 15.7% with the AM portal technique (P = .01) and 10.8% +/ 10.8% in the OI technique (P = .01). Centers of femoral tunnels created by the TT, AM portal, and OI techniques were located at a distance of 3.0 +/- 1.5 mm, 2.1 +/- 0.9 mm, and 1.5 +/- 1.2 mm, respectively, from the ACL footprint center. The femoral tunnel exit location of the AM portal technique on the lateral femoral cortex was closer to the lateral epicondyle than the femoral tunnel exit location of the OI and TT techniques. CONCLUSION: Findings of this study indicate that a larger posterolateral bundle coverage is achieved by the AM portal and OI techniques than by the TT technique. Centers of the tunnels created by the AM portal and OI techniques were closer to the native ACL footprint center than the center of the TT technique tunnel. The incidence of a posterior femoral tunnel exit relative to the lateral epicondyle is higher in the AM portal technique than in the OI and TT techniques. CLINICAL RELEVANCE: For ACL reconstruction using soft tissue grafts, tibial tunnel-independent techniques can produce more anatomic tunnels than the TT technique. PMID- 22302207 TI - The role of myocardial scintigraphy in the assessment of cardiovascular risk in patients with end-stage chronic kidney disease on the waiting list for renal transplantation. AB - BACKGROUND: The usefulness of stress myocardial perfusion scintigraphy for cardiovascular (CV) risk stratification in chronic kidney disease remains controversial. We tested the hypothesis that different clinical risk profiles influence the test. METHODS: We assessed the prognostic value of myocardial scintigraphy in 892 consecutive renal transplant candidates classified into four risk groups: very high (aged>=50 years, diabetes and CV disease), high (two factors), intermediate (one factor) and low (no factor). RESULTS: The incidence of CV events and death was 20 and 18%, respectively (median follow-up=22 months). Altered stress testing was associated with an increased probability of cardiovascular events only in intermediate-risk (one risk factor) patients [30.3 versus 10%, hazard ratio (HR)=2.37, confidence interval (CI) 1.69-3.33, P<0.0001]. Low-risk patients did well regardless of scan results. In patients with two or three risk factors, an altered stress test did not add to the already increased CV risk. Myocardial scintigraphy was related to overall mortality only in intermediate-risk patients (HR=2.8, CI 1.5-5.1, P=0.007). CONCLUSIONS: CV risk stratification based on myocardial stress testing is useful only in patients with just one risk factor. Screening may avoid unnecessary testing in 60% of patients, help stratifying for risk of events and provide an explanation for the inconsistent performance of myocardial scintigraphy. PMID- 22302208 TI - Combination therapy with an angiotensin II receptor blocker and an HMG-CoA reductase inhibitor in experimental subtotal nephrectomy. AB - BACKGROUND: Angiotensin receptor 1 blockers (ARB) are standard nephroprotective drugs in chronic kidney disease. There is less evidence for a nephroprotective effect of HMG-CoA reductase inhibitors (statins) and much less is known about potential benefits of combination therapy. We evaluated the therapeutic potential of a statin alone or in combination with an ARB in experimental chronic kidney disease. METHODS: Subtotally nephrectomized (5/6 Nx) rats were treated early with vehicle, losartan, cerivastatin or losartan/cerivastatin. Expression of messenger RNA (mRNA) was assessed by real-time reverse transcription-polymerase chain reaction. Tissue proteins were localized by immunohistochemistry. Nuclear factor kappaB (NF-kappaB) activation was measured in whole kidneys. RESULTS: In contrast to the sham group, at 6 weeks, vehicle-treated 5/6 Nx rats displayed renal lesions, albuminuria and increased blood pressure, serum creatinine and total kidney NF-kappaB p65 DNA-binding activity and preproendothelin-1, fibronectin and type I and III collagen mRNA. NF-kappaB activation correlated with albuminuria and histological renal injury. Losartan or combination therapy preserved renal function, abrogated albuminuria and improved glomerular and interstitial histology. Cerivastatin alone preserved renal function and improved interstitial injury but did not influence albuminuria, glomerular histology or NF-kappaB activation. Losartan/cerivastatin normalized kidney NF-kappaB activation and extracellular matrix mRNA expression pattern. The effect of losartan alone on these parameters was less intense. All treatments decreased preproendothelin-1 mRNA and preserved interstitial capillaries. CONCLUSIONS: In a chronic kidney disease model, early treatment with either an ARB or a statin preserved renal function although the mechanisms differed. Combination therapy with an ARB and a statin did not confer clear-cut advantages on biochemical and histological parameters over ARB alone, although it further improved the kidney NF-kappaB and gene expression profile. PMID- 22302209 TI - Relationships between muscle size and hardness of the medial gastrocnemius at different ankle joint angles in young men. AB - BACKGROUND: Measurement of muscle hardness is important for objective evaluation of the muscle condition. Muscle hardness may be related to muscle size, but this relationship has not yet been examined. PURPOSE: To examine the relationship between the size and hardness of the medial gastrocnemius muscle (MG) at different ankle joint angles. MATERIAL AND METHODS: Twelve young male subjects comprised the present study. Muscle thickness of the right MG (MT(MG)) was measured by ultrasonography as an index of muscle size. The MT(MG) was determined at 30% of the lower leg length from the popliteal crease to the lateral malleolus. At the same site, muscle hardness of the right MG (MH(MG)) was measured with ultrasound real-time tissue elastography. Both measurements were taken while each subject was instructed to lie in a prone position on a test bench. The right ankle was secured to a handmade apparatus by a non-elastic belt, with the hip and knee joints fully extended and the ankle positioned at +30 degrees , 0 degrees and -20 degrees (0 degrees : neutral position, positive values indicating plantar flexion). RESULTS: There were no significant differences in the MT(MG) among the ankle joint angles whereas the MH(MG) significantly increased as the ankle was moved from plantar flexion to dorsiflexion. As a result, there was a difference in the MT(MG)-MH(MG) relationship between the angles. The MT(MG) significantly correlated with the MH(MG) only at +30 degrees (r = 0.635, P < 0.05) where passive torque around the ankle has been shown to be near zero in previous studies. CONCLUSION: The hardness of the relaxed MG with no passive tension appears to depend on its size. PMID- 22302210 TI - Value of the US BI-RADS final assessment following mastectomy: BI-RADS 4 and 5 lesions. AB - BACKGROUND: Clinical examination is not entirely sufficient for evaluation of the postoperative site for follow-up of patients with mastectomy. A few studies have reported that postoperative follow-up US evaluation allows early detection and proper management of local tumor recurrence. PURPOSE: To evaluate the diagnostic performance of the American College of Radiology (ACR) ultrasonographic (US) Breast Imaging Reporting and Data System (BI-RADS) categories 4 and 5 breast lesions at the mastectomy site. MATERIAL AND METHODS: Our institutional review board approved this study and waived the need for informed consent. We retrospectively reviewed the consecutive post-mastectomy US exams for palpable and non-palpable lesions in the post-mastectomy chest wall that were categorized as BI-RADS 4 (subcategorized 4a, 4b, and 4c) or 5 between January 2007 and April 2010. The positive predictive value (PPV) for final assessment was evaluated. RESULTS: From 2681 post-mastectomy US examinations, we obtained a study population of 50 patients with 50 lesions (20 palpable, 30 non-palpable). There were nine (45%) malignancies among the palpable lesions and six (20%) malignancies among the non-palpable lesions. The palpability showed no significant correlation with malignancy in overall subcategorization (P >0.05). The PPVs of categories 4 and 5 were 14.3% for category 4a, 62.5% for category 4b, 100% for category 4c, and 100% for category 5. CONCLUSION: The ACR US BI-RADS categorization of 4a, 4b, 4c, and 5 for breast lesions at the mastectomy site is a feasible method for predicting local recurrence. All lesions should be managed according to US characteristics during evaluation of local recurrence at the mastectomy site, regardless of palpability. PMID- 22302211 TI - Community-based case management for the prevention of suicide reattempts in Kaohsiung, Taiwan. AB - Although a previous suicide attempt constitutes a major risk factor for an eventual completed suicide, few interventions specifically designed to prevent suicide reattempt shave been evaluated. The aim of this study was to determine the effectiveness of case management for the prevention of suicide reattempts. A total of 4,765 subjects with a recent suicide attempt referred from medical and non-medical organizations were consecutively recruited from July 2006 to June 2008. The suicide prevention program of Kaohsiung Suicide Prevention Center (KSPC)provided case management and followed up suicide attempt cases for 6 months. Survival analysis showed that the risk of suicide reattempt was significantly lower in the case management group than in the non-contact group throughout a six-month follow-up period (hazard ratio =2.93; 95% CI = 2.47-3.47). The hazard ratio (HR) of the Cox proportional hazard model for sex was 0.77 (95%CI = 0.65-0.91). Case management appears to be effective in preventing suicide reattempts in patients with a recent prior attempt. In addition, case management appeared to be more beneficial in preventing suicide reattempts in male subjects. PMID- 22302212 TI - The Alabama Coalition for a Healthier Black belt: a proof of concept project. AB - The Alabama Coalition for a Healthier Black was a demonstration of concept project. This paper is a descriptive and qualitative overview of this 2.5 year project. Limited key project results are reported here. Located in the rural Black Belt region of Alabama this coalition had several key aims: to develop a collaboration between primary care and mental health care through co-location of services; use of video-conferencing capability to provide mental health services more efficiently; enhanced training in rural healthcare; and development of stigma reduction campaigns along with other coalition partner specific initiatives. Co-location and telepsychiatry implementation produced the major challenges and resulting adaptations to original aims. Despite many challenges these new service patterns were put into place and appear to be sustainable. PMID- 22302213 TI - Early intervention services for psychosis and time until application for disability income support: a survival analysis. AB - Ensuring the financial security of individuals recovering from first episode psychosis is imperative, but disability income programs can be powerful disincentives to employment, compromising the social and occupational aspects of recovery. Survival analysis and Cox regression analysis were used to examine the rate at which individuals served by early intervention for psychosis (EIP) services apply for government disability income benefits and factors that predict rate of application. Health records for 558 individuals served by EIP programs were reviewed. Within the first year of receiving services 30% will make application for disability income; 60% will do so by 5 years. Rate of application is predicted by rate of hospital admission, financial status and engagement in productivity roles at the time of entry to EIP service. The findings suggest the need to examine the extent to which the recovery goals of EI services are undermined by early application for government income support. They also suggest the need to develop best practice guidelines related to ensuring the economic security of individuals served. PMID- 22302214 TI - Secular versus religious norms against smoking: which is more important as a driver of quitting behaviour among Muslim Malaysian and Buddhist Thai smokers? AB - BACKGROUND: This paper prospectively examined two kinds of social normative beliefs about smoking, secular versus religious norms. PURPOSE: The purpose of this paper is to determine the relative importance of these beliefs in influencing quitting behaviour among Muslim Malaysian and Buddhist Thai smokers. METHODS: Data come from 2,166 Muslim Malaysian and 2,463 Buddhist Thai adult smokers who participated in the first three waves of the International Tobacco Control Southeast Asia project. Respondents were followed up about 18 months later with replenishment. Respondents were asked at baseline about whether their society disapproved of smoking and whether their religion discouraged smoking, and those recontacted at follow-up were asked about their quitting activity. RESULTS: Majority of both religious groups perceived that their religion discouraged smoking (78% Muslim Malaysians and 86% Buddhist Thais) but considerably more Buddhist Thais than Muslim Malaysians perceived that their society disapproved of smoking (80% versus 25%). Among Muslim Malaysians, religious, but not societal, norms had an independent effect on quit attempts. By contrast, among the Buddhist Thais, while both normative beliefs had an independent positive effect on quit attempts, the effect was greater for societal norms. The two kinds of normative beliefs, however, were unrelated to quit success among those who tried. CONCLUSIONS: The findings suggest that religious norms about smoking may play a greater role than secular norms in driving behaviour change in an environment, like Malaysia where tobacco control has been relatively weak until more recently, but, in the context of a strong tobacco control environment like Thailand, secular norms about smoking become the dominant force. PMID- 22302215 TI - Fatal thromboembolism following physical restraint in a patient with schizophrenia. AB - Fatal thromboembolism during physical restraint in patients suffering from psychotic disorders is a very rare occurrence. In the case we present here, the criteria used in forensic pathology for the age determination of venous thrombi are applied to a case of pulmonary embolism in a patient suffering from schizophrenia who died after physical restraint. The possible association between conventional antipsychotic drugs and deep venous thrombosis, followed by pulmonary embolism, in a man with no predisposing risk factors, as well as the question concerning the appropriateness of medical care, are discussed. PMID- 22302216 TI - Associations between violent video gaming, empathic concern, and prosocial behavior toward strangers, friends, and family members. AB - Exposure to media violence, including violent video gaming, can have a cognitive desensitization effect, lowering empathic concern for others in need. Since emerging adulthood offers increased opportunities to volunteer, strengthen relationships, and initiate new relationships, decreases in empathic concern and prosocial behavior may prove inhibitive to optimal development during this time. For these reasons, the current study investigated associations between violent video gaming, empathic responding, and prosocial behavior enacted toward strangers, friends, and family members. Participants consisted of 780 emerging adults (M age = 19.60, SD = 1.86, range = 18-29, 69% female, 69% Caucasian) from four universities in the United States. Results showed small to moderate effects between playing violent video gaming and lowered empathic concern for both males and females. In addition, lowered empathic concern partially mediated the pathways between violent video gaming and prosocial behavior toward all three targets (at the level of a trend for females), but was most strongly associated with lower prosocial behavior toward strangers. Discussion highlights how violent video gaming is associated with lower levels of prosocial behavior through the mechanism of decreased empathic concern, how this association can affect prosocial behavior differently across target, and finally what implications this might have for development during emerging adulthood. PMID- 22302217 TI - Invited commentary: seeking a coherent strategy in our response to homeless and street-involved youth: a historical review and suggested future directions. AB - This invited commentary seeks to encourage a critical dialogue about youth homelessness that might assist in re-energizing a field that seems increasingly stagnant with a research body focused primarily on analyses of risk, hopelessly inadequate policy frameworks in most cities, diminishing funds for services, and decreasing media attention. Reviewing major trends in research and public responses to youth homelessness in the past century, I propose that there exist three major culturally-bound dimensions from which we construct our understanding of and responses to youth homelessness. These dimensions, which are considered in a transactional framework, are the scope of responsibility, the location of moral responsibility, and the amount of agency attributed to the youth. In this review I highlight the manner in which our historically binary and uncritical understanding of these dimensional characterizations of youth homelessness has led to major lapses in the effectiveness of our collective efforts to address this problem. I highlight gaps in the existing body of research literature and provide this framework, arguing that a strategic and cohesive response is vital if we are to move from reiterations of risk and hackneyed calls for prevention strategies to the generation of meaningful solutions. PMID- 22302218 TI - Thiol-ene reaction: a versatile tool in site-specific labelling of proteins with chemically inert tags for paramagnetic NMR. AB - Site-specific tagging of proteins with paramagnetic lanthanides generates valuable long-range structure restraints for structural biology by NMR spectroscopy. We show that the thiol-ene addition reaction offers a powerful tool for tagging proteins in a chemically stable manner with very small lanthanide tags. PMID- 22302219 TI - Temporal and spatial variability in the distribution of Vibrio vulnificus in the Chesapeake Bay: a hindcast study. AB - Vibrio vulnificus, an estuarine bacterium, is the causative agent of seafood related gastroenteritis, primary septicemia, and wound infections worldwide. It occurs as part of the normal microflora of coastal marine environments and can be isolated from water, sediment, and oysters. Hindcast prediction was undertaken to determine spatial and temporal variability in the likelihood of occurrence of V. vulnificus in surface waters of the Chesapeake Bay. Hindcast predictions were achieved by forcing a multivariate habitat suitability model with simulated sea surface temperature and salinity in the Bay for the period between 1991 and 2005 and the potential hotspots of occurrence of V. vulnificus in the Chesapeake Bay were identified. The likelihood of occurrence of V. vulnificus during high and low rainfall years was analyzed. From results of the study, it is concluded that hindcast prediction yields an improved understanding of environmental conditions associated with occurrence of V. vulnificus in the Chesapeake Bay. PMID- 22302220 TI - Synthesis of pyrrolyldipyrrinato BF2 complexes by oxidative nucleophilic substitution of boron dipyrromethene with pyrrole. AB - Direct oxidative nucleophilic substitution of the 3-hydrogen of BODIPY dyes by pyrrole has been developed under reflux condition under oxygen, from which a series of pyrrolyldipyrrinato BF(2) complexes 1a-h, as extended BODIPYs, have been synthesized. Most of these BODIPYs show strong fluorescence emissions at wavelengths over 600 nm in six solvents of different polarity. Removal of the BF(2) group from BODIPY 1e gave the corresponding free base pyrrolyldipyrrin 7 as an analog of the natural product prodigiosin, in high yield. PMID- 22302221 TI - Highly sensitive electrochemical detection of proteins using aptamer-coated gold nanoparticles and surface enzyme reactions. AB - A novel electrochemical detection methodology is described for the femtomolar detection of proteins which utilizes both DNA aptamer-functionalized nanoparticles and a surface enzymatic reaction. Immunoglobulin E (IgE) was used as a model protein biomarker, which possesses two distinct epitopes for antibody (anti-IgE) and DNA aptamer binding. A surface sandwich assay format was utilized involving the specific adsorption of IgE onto a gold electrode surface that was pre-modified with a monolayer of aptamer-nanoparticle conjugates followed by the specific interaction of alkaline phosphatase (ALP) conjugated anti-IgE. To clearly demonstrate the signal enhancement associated with nanoparticle use, anodic current measurements of the ALP catalyzed oxidation of the enzyme substrate 4-aminophenylphosphate (APP) were also compared with electrode surfaces upon which the aptamer was directly attached. The detection of an unlabelled protein at concentrations as low as 5 fM is a significant improvement compared to conventional electrochemical-based immunoassay approaches and provides a foundation for the practical use and incorporation of nanoparticle-enhanced detection into electrochemical biosensing technologies. PMID- 22302222 TI - Nuclear DYW-type PPR gene families diversify with increasing RNA editing frequencies in liverwort and moss mitochondria. AB - RNA editing in mitochondria and chloroplasts of land plants alters transcript sequences by site-specific conversions of cytidines into uridines. RNA editing frequencies vary extremely between land plant clades, ranging from zero in some liverworts to more than 2,000 sites in lycophytes. Unique pentatricopeptide repeat (PPR) proteins with variable domain extension (E/E+/DYW) have recently been identified as specific editing site recognition factors in model plants. The distinctive functions of these PPR protein domain additions have remained unclear, although deaminase function has been proposed for the DYW domain. To shed light on diversity of RNA editing and DYW proteins at the origin of land plant evolution, we investigated editing patterns of the mitochondrial nad5, nad4, and nad2 genes in a wide sampling of more than 100 liverworts and mosses using the recently developed PREPACT program (www.prepact.de) and exemplarily confirmed predicted RNA editing sites in selected taxa. Extreme variability in RNA editing frequency is seen both in liverworts and mosses. Only few editings exist in the liverwort Lejeunea cavifolia or the moss Pogonatum urnigerum whereas up to 20% of cytidines are edited in the liverwort Haplomitrium mnioides or the moss Takakia lepidozioides. Interestingly, the latter are taxa that branch very early within their respective clades. Amplicons targeting the E/E+/DYW domains and subsequent random clone sequencing show DYW domains among bryophytes to be highly conserved in comparison with their angiosperm counterparts and to correlate well with RNA editing frequencies regarding their diversities. We propose that DYW proteins are the key players of RNA editing at the origin of land plants. PMID- 22302223 TI - A ternary Cu-Sn-S cluster complex--(NBu4)[Cu19S28(SnPh)12(PEt2Ph)3]. AB - Reaction of a mixture of CuCl, PhSnCl(3) and PEt(2)Ph with S(SiMe(3))(2) in THF resulted initially in the unexpected synthesis of the ionic, mixed copper-tin sulfide cluster [Li(thf)(4)][Cu(19)S(28)(SnPh)(12)(PEt(2)Ph)(3)] in low yields. However, by adding NBu(4)Cl to the reaction solutions we were able to selectively synthesize the structurally similar cluster ion in (NBu(4))[Cu(19)S(28)(SnPh)(12)(PEt(2)Ph)(3)]. Structural characterization by single crystal X-ray analysis reveals that the cluster anions consist in principle of a copper sulfide core decorated by PhSn(3+) groups. Although additional phosphine ligands are attached to copper atoms the clusters possess an open 'Cu(3)S(3)' face mostly protected by the [Li(thf)(4)](+) and (NBu(4))(+) counterions in the crystal structure. The cluster (NBu(4))[Cu(19)S(28)(SnPh)(12)(PEt(2)Ph)(3)] displays near-infrared, temperature dependent photoluminescence at ~820-930 nm in the solid state, which is especially bright at temperatures below ~100 K. PMID- 22302224 TI - A methodology for evaluating and ranking water quantity indicators in support of ecosystem-based management. AB - Ecosystem-based Management (EBM) is an approach that includes different management priorities and requires a balance between anthropogenic and ecological resource demands. Indicators can be used to monitor ecosystem status and trends, and assess whether projects and/or programs are leading to the achievement of management goals. As such, the careful selection of a suite of indicators is a crucial exercise. In this paper we describe an indicator evaluation and selection process designed to support the EBM approach in Puget Sound. The first step in this process was the development of a general framework for selecting indicators. The framework, designed to transparently include both scientific and policy considerations into the selection and evaluation process, was developed and then utilized in the organization and determination of a preliminary set of indicators. Next, the indicators were assessed against a set of nineteen distinct criteria that describe the model characteristics of an indicator. A literature review was performed for each indicator to determine the extent to which it satisfied each of the evaluation criteria. The result of each literature review was summarized in a numerical matrix, allowing comparison, and demonstrating the extent of scientific reliability. Finally, an approach for ranking indicators was developed to explore the effects of intended purpose on indicator selection. We identified several sets of scientifically valid and policy-relevant indicators that included metrics such as annual-7 day low flow and water system reliability, which are supportive of the EBM approach in the Puget Sound. PMID- 22302225 TI - Effects of trampling limitation on coastal dune plant communities. AB - Sandy coastlines are sensitive ecosystems where human activities can have considerable negative impacts. In particular, trampling by beach visitors is a disturbance that affects dune vegetation both at the species and community level. In this study we assess the effects of the limitation of human trampling on dune vegetation in a coastal protected area of Central Italy. We compare plant species diversity in two recently fenced sectors with that of an unfenced area (and therefore subject to human trampling) using rarefaction curves and a diversity/dominance approach during a two year study period. Our results indicate that limiting human trampling seems to be a key factor in driving changes in the plant diversity of dune systems. In 2007 the regression lines of species abundance as a function of rank showed steep slopes and high Y-intercept values in all sectors, indicating a comparable level of stress and dominance across the entire study site. On the contrary, in 2009 the regression lines of the two fenced sectors clearly diverge from that of the open sector, showing less steep slopes. This change in the slopes of the tendency lines, evidenced by the diversity/dominance diagrams and related to an increase in species diversity, suggests the recovery of plant communities in the two fences between 2007 and 2009. In general, plant communities subject to trampling tended to be poorer in species and less structured, since only dominant and tolerant plant species persisted. Furthermore, limiting trampling appears to have produced positive changes in the dune vegetation assemblage after a period of only two years. These results are encouraging for the management of coastal dune systems. They highlight how a simple and cost-effective management strategy, based on passive recovery conservation measures (i.e., fence building), can be a quick (1-2 years) and effective method for improving and safeguarding the diversity of dune plant communities. PMID- 22302226 TI - Health care costs: how do we decide value? When do we decide? How do we particularize the decisions? PMID- 22302228 TI - The ARCAD clinical trials program: an update and invitation. PMID- 22302227 TI - Changes in biomarkers of inflammation and angiogenesis during androgen deprivation therapy for prostate cancer. AB - INTRODUCTION: Angiogenesis and inflammation are both important to the pathogenesis of malignancies. Androgen deprivation therapy (ADT) for prostate cancer causes drastic hormonal changes that alter both disease and host factors. We measured inflammatory and angiogenic biomarkers in ADT-treated and control groups of men with prostate cancer. MATERIALS AND METHODS: Baseline and 12-week plasma samples were collected from 37 ADT-naive men with locally advanced or recurrent prostate cancer. Of those, 23 initiated ADT with a gonadotropin releasing hormone (GnRH) agonist and 14 served as nontreatment controls. Samples were tested for a panel of angiogenic and inflammatory biomarkers. RESULTS: The treatment group had significantly higher concentrations of the inflammatory biomarkers interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and stromal cell-derived factor (SDF)-1alpha. None of the angiogenic biomarkers were significantly different between the groups at baseline. Among patients with a short prostate-specific antigen (PSA) doubling time (<6 months), the proangiogenic factor basic fibroblast growth factor (bFGF) was lower at baseline. In the treatment group, plasma placental growth factor (PlGF) increased and IL-6 decreased after 12 weeks of ADT. Moreover, the treatment group continued to have significantly higher concentrations of the inflammatory biomarkers IL-1beta, IL 8, and SDF-1alpha as well as bFGF than controls. DISCUSSION: These men were characterized by elevations in several traditional markers of aggressive disease and also by higher levels of several inflammatory biomarkers. Although ADT decreased IL-6 levels, IL-1beta, IL-8, and SDF-1alpha remained significantly higher than in controls. The role of these biomarkers should be further explored. PMID- 22302229 TI - Call it cancer. PMID- 22302230 TI - Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function. PMID- 22302231 TI - Assessing the real-world cost-effectiveness of adjuvant trastuzumab in HER-2/neu positive breast cancer. AB - BACKGROUND: Among women with surgically removed, high-risk HER-2/neu-positive breast cancer, trastuzumab has demonstrated significant improvements in disease free and overall survival. The objective of this study is to evaluate the cost effectiveness of the currently recommended 12-month adjuvant protocol of trastuzumab using a Markov modeling approach and real-world cost data. METHODS: A 10-health-state Markov model tracked patients' quarterly transitions between health states in the local and advanced states of breast cancer. Clinical data were obtained from the joint analysis of the National Surgical Adjuvant Breast and Bowel Project and North Central Cancer Treatment Group, as well as from the metastatic study conducted by Norum et al. Clinical outcomes were adjusted for quality of life using utility estimates published in a systematic review. Real cost data were obtained from the British Columbia Cancer Agency and were evaluated from a payer perspective. Costs and utilities were discounted at 5% per year, respectively, for a 28-year time horizon. RESULTS: In the base case analysis, treatment with a 12-month adjuvant trastuzumab regimen resulted in a gain of 1.38 quality-adjusted life years or 1.17 life years gained at a cost of $18,133 per patient. Thus, the cost per QALY gained for the base case is $13,095. Cost per LYG is $15,492. CONCLUSIONS: Over the long term, treatment of HER-2/neu mutation positive breast cancer with a 12-month protocol of trastuzumab in the adjuvant setting is predicted to be cost-effective in a Canadian context. PMID- 22302232 TI - Spatiotemporal expression of testicular protein kinase 1 after rat sciatic nerve injury. AB - Testicular protein kinase 1 (TESK1), a serine/threonine kinase, has been found expressing in various tissues and cell lines. Previous reports have shown that TESK1 plays an important role in regulating actin reorganization of spreading cell on fibronectin via phosphorylating cofilin. Because of the importance of actin reorganization in radial sorting and remyelination of peripheral nerve regeneration, we investigated the spatiotemporal expression of TESK1 in a rat sciatic nerve crush model. We observed that sciatic nerve crush resulted in a significant upregulation of TESK1 from 5 days to 2 weeks and subsequent return to the control level at 4 weeks. At its peak expression, TESK1 expressed mainly in both Schwann cells (SCs) and macrophages of the distal sciatic nerve segment, but had few colocalization in axons. In addition, upregulation of TESK1 was approximately in parallel with Oct-6, and numerous SCs expressing TESK1 were Oct 6 positive. Experiments with Schwann cell primary cultures revealed that TESK1 accumulated at F-actin-rich lamellipodia of the cell periphery when SCs were plated on fibronectin, whereas it was distributed in the cytoplasm in the case of non-stimulated cells. Thus, these findings suggest that TESK1 plays important roles in promyelinating SCs, potentially through subcellular localization change and participation in integrin-mediated actin reorganization. PMID- 22302233 TI - Evaluation of a mindfulness-based intervention program to decrease blood pressure in low-income African-American older adults. AB - Hypertension affects a large proportion of urban African-American older adults.While there have been great strides in drug development, many older adults do not have access to such medicines or do not take them. Mindfulness-based stress reduction (MBSR)has been shown to decrease blood pressure in some populations. This has not been tested in low-income, urban African-American older adults. Therefore, the primary purpose of this pilot study was to test the feasibility and acceptability of a mindfulness-based program for low income, minority older adults provided in residence. The secondary purpose was to learn if the mindfulness-based program produced differences in blood pressure between the intervention and control groups. Participants were at least 62 years old and residents of a low-income senior residence. All participants were African American, and one was male.Twenty participants were randomized to the mindfulness based intervention or a social support control group of the same duration and dose. Blood pressure was measured with the Omron automatic blood pressure machine at baseline and at the end of the 8-week intervention. A multivariate regression analysis was performed on the difference in scores between baseline and post intervention blood pressure measurements, controlling for age,education, smoking status, and anti-hypertensive medication use. Effect sizes were calculated to quantify the magnitude of the relationship between participation in the mindfulness-based intervention and the outcome variable, blood pressure. Attendance remained 980%in all 8 weeks of both the intervention and the control groups. The average systolic blood pressure decreased for both groups post intervention. Individuals in the intervention group exhibited a 21.92-mmHg lower systolic blood pressure compared to the social support control group post intervention and this value was statistically significant(p=0.020). The average diastolic blood pressure decreased in the intervention group postintervention,but increased in the social support group. Individuals in the intervention group exhibited a 16.70-mmHg lower diastolic blood pressure compared to the social support group post-intervention, and this value was statistically significant (p=0.003).Older adults are at a time in life when a reflective, stationary intervention, delivered in residence, could be an appealing mechanism to improve blood pressure. Given our preliminary results, larger trials in this hypertensive study population are warranted. PMID- 22302234 TI - Environmental Audits of Friendliness toward Physical Activity in Three Income Levels. AB - An important research area is the relationship among income status, health, and the environment. This study examined the relationships among income levels, features of the environment and friendliness toward physical activity. We investigated whether low-, middle-, and high-income neighborhoods differ in terms of four environmental characteristics that affect the degree to which an area is conducive to physical activity: population density, land use diversity, street design, and physical disorder in the environment. In a large, urban southwestern county, 30 block groups were randomly selected to represent low-, middle-, and high-income neighborhoods. Using the St. Louis Environmental Checklist Audit, walking audits were conducted and analyzed. The low-income neighborhoods had significantly greater density and land use diversity than the high-income neighborhoods. High- and middle-income neighborhoods had significantly fewer manifestations of physical disorder and incivility than low-income neighborhoods. Features of physical activity-promoting environments were found in each income level neighborhood. PMID- 22302235 TI - Computer-aided volumetric analysis as a sensitive tool for the management of incidental meningiomas. AB - INTRODUCTION: Meningiomas are typically slow-growing lesions that, depending on the location, can be relatively benign. Knowing their exact rate of growth can be helpful in determining whether surgery is necessary. METHODS: In this study we retrospectively reviewed the meningioma practices of the two senior authors (JR, MR). Our goal was to measure meningioma growth using a variety of methods (linear using diameters, and volumetric using the computer-aided perimeter and cross sectional diameter methods) to compare rates of growth among the methods. Of 295 meningioma patients seen over an 8-year period, we identified a cohort of 31 patients with at least 30 months of follow-up. Volumes were calculated using medical imaging software with T1 post-contrast magnetic resonance imaging. Doubling times and growth rates were calculated. RESULTS: Of the 31 patients, 26 (84%) were shown to have growing meningiomas. The perimeter methodology measured higher growth rates than the diameter method for both doubling times as well as percentage annual growth (p<0.01). The mean doubling time was 13.4 years (range, 2.1-72.8 years) and 17.9 years (range, 4-92.3 years) comparing perimeter and diameter methods, respectively. The mean percentage of annual growth was 15.2% (range, 1.8-61.7%) and 5.6% (range, 0.7-12.2%), comparing perimeter and diameter methods, respectively. Linear growth was calculated at 0.7 mm/year. CONCLUSION: Overall, we found that computer-aided perimeter methods showed a more accurate picture of tumor progression than traditional methods, which generally underestimated growth. PMID- 22302236 TI - Single low dose adjuvant gamma knife radiosurgery for thyrotropin secreting pituitary adenoma. PMID- 22302237 TI - Types and severity of operated supraclavicular brachial plexus injuries caused by traffic accidents. AB - BACKGROUND: Brachial plexus injuries occur in up to 5% of polytrauma cases involving motorcycle accidents and in approximately 4% of severe winter sports injuries. One of the criteria for a successful operative therapy is the type of lesion. Upper plexus palsy has the best prognosis, whereas lower plexus palsy is surgically untreatable. The aim of this study was to evaluate a group of patients with brachial plexus injury caused by traffic accidents, categorize the injuries according to type of accident, and look for correlations between type of palsy (injury) and specific accidents. METHODS: A total of 441 brachial plexus reconstruction patients from our department were evaluated retrospectively(1993 to 2011). Sex, age, neurological status, and the type and cause of injury were recorded for each case. Patients with BPI caused by a traffic accident were assessed in detail. RESULTS: Traffic accidents were the cause of brachial plexus injury in most cases (80.7%). The most common type of injury was avulsion of upper root(s) (45.7%) followed by rupture (28.2%), complete avulsion (16.9%) and avulsion of lower root(s) (9.2%). Of the patients, 73.9% had an upper,22.7% had a complete and only 3.4% had a lower brachial plexus palsy. The main cause was motorcycle accidents(63.2%) followed by car accidents (23.5%), bicycle accidents(10.7%) and pedestrian collisions (3.1%) (p<0.001).Patients involved in car accidents had a higher percentage of lower avulsion (22.7%) and a lower percentage of upper avulsion (29.3%), whereas cyclists had a higher percentage of upper avulsion (68.6%) based on the data from the entire group of patients (p<0.001). Lower plexus palsy was significantly increased in patients after car accidents (9.3%,p<0.05). In the two main groups (car and motorcycle accidents),significantly more upper and fewer lower palsies were present. In the bicycle accident group, upper palsy was the most common (89%). CONCLUSION: Study results indicate that the most common injury was an upper plexus palsy. It was characteristic of bicycle accidents, and significantly more common in car and motorcycle accidents. The results also indicate that it is important to consider the potential of a brachial plexus injury after serious traffic accidents and to examine both upper extremities in detail even if some motor function is preserved. PMID- 22302238 TI - Intellectual disability nursing in Ireland: identifying its development and future. AB - As a profession, intellectual disability nursing has often come under scrutiny and been called into question. Since its inception as an individual nursing profession in 1959 in Ireland, both education and service provision philosophies have changed over time. These changes have been in response to national and international reports and changing attitudes. The changes have led to the current position where intellectual disability nurse education in Ireland is a four-year undergraduate course. As the discipline of intellectual disability nursing is unique to Ireland and the United Kingdom, there is a responsibility on intellectual disability nurses to identify their unique identity and their responses to the demands of changing services. This article traces the development of intellectual disability nursing in Ireland and identifies implications for the future. PMID- 22302239 TI - Examining pica in NYC pregnant women with elevated blood lead levels. AB - We sought to describe the impact of pica, the craving for and intentional ingestion of substances not defined as food, as a risk factor for lead poisoning in New York City (NYC) pregnant women. In order to describe pregnant women with elevated blood lead levels (BLLs) who report pica, NYC health department data from 491 cases of lead-poisoned pregnant women from January 2001 to June 2009 were reviewed. Descriptive frequencies were obtained for women reporting pica. Data were compared between women reporting and not reporting pica. In NYC, of the 43 (9%) lead-poisoned pregnant women reporting pica, 42 (97.7%) were immigrants and 28 (64.6%) had consumed soil. Compared to lead-poisoned pregnant women not reporting pica, women reporting pica had higher peak BLLs (29.5 vs. 23.8 MUg/dL, P = 0.0001), were more likely to have had a BLL >= 45 MUg/dL (OR = 3.3, 95% CI, 1.25, 8.68) and receive chelation (OR = 10.88, 95% CI, 1.49, 79.25), more likely to have emigrated from Mexico (OR = 3.05, 95% CI, 1.38-6.72), and less likely to have completed high school (OR = indeterminate; 0 vs. 34%; P = 0.003). Among NYC lead-poisoned pregnant women, pica was associated with higher peak BLLs. Providers in NYC, and possibly other urban settings, should be vigilant and question pregnant women, especially immigrants, about pica and strongly consider testing this at-risk population for lead poisoning. PMID- 22302240 TI - Risk assessment and management of Chlamydia psittaci in poultry processing plants. AB - Chlamydia psittaci causes respiratory disease in poultry and can be transmitted to humans. Historical outbreaks of psittacosis in poultry workers indicated the need for higher awareness and an efficient risk assessment and management. This group reviewed relevant previous research, practical guidelines, and European directives. Subsequently, basic suggestions were made on how to assess and manage the risk of psittacosis in poultry processing plants based on a classical four step approach. Collective and personal protective measures as well as the role of occupational medicine are described. Despite the finding that exposure is found in every branch, abattoir workstations seem to be associated with the highest prevalence of psittacosis. Complete eradication is difficult to achieve. Ventilation, cleaning, hand hygiene, and personal protective equipment are the most important protective measures to limit and control exposure to C. psittaci. Adequate information, communication, and health surveillance belong to the responsibilities of the occupational physician. Future challenges lay in the rigorous reporting of infections in both poultry and poultry workers and in the development of an avian and human vaccine. PMID- 22302241 TI - Antioxidants and chronic pancreatitis: theory of oxidative stress and trials of antioxidant therapy. AB - Chronic pancreatitis (CP) is an inflammatory disease characterized by the progressive destruction of pancreatic tissue and resulting in pancreatic exocrine and endocrine insufficiency. Increased oxidative stress has been implicated as a potential mechanism in its etiology and pathology. A number of studies have demonstrated that CP patients have a compromised antioxidant status, which may be a contributing factor to the enhanced oxidative state associated with the disease. Nutrition is an essential consideration in the treatment of CP, especially since diet is a source of several antioxidants and cofactors required for the production of cellular antioxidant enzymes. Many CP patients have an inadequate intake of macro and micronutrients because of abdominal pain and discomfort, which often increase postprandially and discourage eating. Exocrine insufficiency leads to further complications by preventing adequate digestion and absorption of ingested food, thus causing even greater deficiencies and impairment of antioxidant status. The aims of this article are to review the oxidative stress model of CP and to examine the evidence for nutrition, and, particularly, antioxidants, in the treatment of CP. PMID- 22302242 TI - Myosin light chain kinase is involved in the mechanism of gastrointestinal dysfunction in diabetic rats. AB - BACKGROUND: It is well established that smooth muscle contractility is regulated by an elevation of cytosolic Ca(2+) via myosin light chain phosphorylation, which is activated by myosin light chain kinase (MLCK). Recently, MLCK has been demonstrated to play an important role in smooth muscle contraction and normal gastrointestinal motility. AIMS: The aim of our study is to investigate whether MLCK is involved in the mechanism of gastrointestinal dysfunction and the ameliorating effects of insulin on gastrointestinal dysfunction in diabetic rats. METHODS: A diabetic rat model was established by an intravenous injection with streptozotocin. Rats were randomized into three groups: control group, diabetic group, and insulin-treated group. The gastrointestinal functions were assessed in terms of gastric emptying and intestinal transit. The expression of MLCK in the pylorus and ileum of the three groups was determined by real-time polymerase chain reaction (PCR) and Western blot methods. RESULTS: The diabetic group exhibited a significant delay in gastric emptying and intestinal transit than the control group. Insulin treatment significantly ameliorated the gastric emptying and intestinal transit in diabetic rats. The expression levels of MLCK in the pylorus and ileum of the diabetic group were both significantly decreased compared with the control group, and the changes of MLCK expression in these tissues of diabetic rats were partially reversed after treatment with insulin. CONCLUSIONS: Decreased expression of MLCK in gastrointestinal tissues could be a possible cause for gastrointestinal dysfunction. Insulin may partly ameliorate gastrointestinal dysfunction by restoring the expression of MLCK. PMID- 22302243 TI - Liver stiffness measurement using acoustic radiation force impulse (ARFI) elastography and effect of necroinflammation. AB - BACKGROUND: Acoustic radiation force impulse (ARFI) elastography can be used to assess the degree of liver fibrosis. AIM: We evaluated the performance of ARFI elastography in assessment of liver fibrosis and compared it with the performance of aspartate aminotransferase-to-platelet ratio index (APRI) and transient elastography with Fibroscan (FS). METHODS: We prospectively analyzed 250 consecutive patients who underwent liver biopsy and ARFI from June 2010 to May 2011. Reliable FS values were obtained for 97 (38.8%) patients. RESULTS: The mean age of patients (147 male and 103 female) was 46.6 years. Liver stiffness values obtained by use of ARFI elastography significantly correlated with histological fibrosis stage (R = 0.575, P < 0.001). Area under the receiver operating characteristics curves (AUROCs) of ARFI elastography for predicting significant fibrosis (>=F2) and cirrhosis (F4) was 0.74 (95% confidence interval [CI], 0.64 0.86, P = 0.001) and 0.79 (95% CI, 0.67-0.91, P = 0.001), respectively, and those for APRI were 0.69 (95% CI, 0.58-0.79, P = 0.001) and 0.76 (95% CI, 0.64-0.85, P < 0.001), respectively. The optimum cutoff values for ARFI elastography were 1.13 m/s for >=F2 and 1.98 m/s for F4; these decreased to 1.09 m/s for >=F2 and 1.81 m/s for F4 when 131 patients with normal alanine aminotransferase (ALT) were selected. In the sub-group of 97 patients with reliable FS values, the performance in predicting >=F2 or F4 was equivalent between ARFI elastography and FS. CONCLUSIONS: ARFI elastography is a reliable surrogate marker of liver fibrosis, if its relationship with biochemical markers, for example ALT level, is taken into account. PMID- 22302245 TI - Letter in response to the recently published study: prophylactic pancreatic stents: does size matter? A comparison of 4-Fr and 5-Fr stents in reference to post-ERCP pancreatitis and migration rate. PMID- 22302244 TI - Diabetes mellitus is an independent risk factor for colorectal cancer. AB - BACKGROUND: Epidemiological studies have suggested positive associations between diabetes and colorectal cancer. However, the findings were inconsistent, especially regarding specific sex or cancer subsite. AIMS: To conduct a systematic review with meta-analysis to examine the association of diabetes mellitus with risk of colorectal cancer and to investigate whether the association is dependent on sex, cancer subsite, race/ethnicity, or duration of diabetes. METHODS: Relevant studies were identified by searching Pubmed to May 12, 2011. The reference lists of identified articles were also reviewed. Two authors independently selected the studies and extracted relevant data. The study quality was assessed. RESULTS: Thirty-nine studies (28 cohort studies and 11 case control studies) were included in the final analysis. Compared with non-diabetic subjects, the pooled risk estimate of colorectal cancer for diabetic subjects was 1.29 (95% CI = 1.23-1.35). The subgroup analyses revealed that the risk was significantly increased for both genders, for every cancer subsite, and for both short duration and long duration of diabetes. Exposure to diabetes increased the risk of colorectal cancer for White and Asian, whereas there was no evidence of such an association either among Black or native Hawaiians. CONCLUSIONS: Our results confirmed that subjects with diabetes are at modestly increased risk of developing colorectal cancer. PMID- 22302246 TI - Impairment of gastric nitrergic and NRF2 system in apolipoprotein E knockout mice. AB - BACKGROUND AND AIM: Gastric motility dysfunction is most commonly seen in diabetic and idiopathic gastroparesis patients. Recently we reported that impaired nitrergic relaxation and a reduced NO (nitric oxide) bioavailability were responsible for gastric motility dysfunction in diabetic female rats. One of the main factors involved in the inactivation of the nitrergic system is oxidative stress commonly seen in diabetic patients. Hyperlipidemia may also be one of the detrimental causes for impaired gastric motility associated with diabetes. In the current study, we investigated whether apolipoprotein E knockout mice (ApoE-KO), an oxidative stress animal model with a hyperlipidemia burden, also displays an impaired nitrergic system. To test this, nitrergic relaxation (AUC/mg tissue) was measured at 2 Hz through electric field stimulation using gastric pyloric strips prepared from C57BL WT or ApoE-KO female mice. Protein expression was determined by Western blots. RESULTS: Nitrergic relaxation was reduced in gastric strips from ApoE-KO versus WT mice. Protein levels of nNOS (neuronal nitric oxide synthase), GCH-1 (GTP cyclohydrolase 1), Nrf2 (nuclear factor E-2 related factor 2) and GCSc (glutamate-cysteine ligase catalytic) were also reduced in ApoE-KO compared to controls, with no significant change in GCSm (glutamate-cysteine ligase modifier) and HO-1 (heme oxygenase 1). The activities of DHFR (dihydrofolate reductase) and antioxidant enzymes were also reduced in ApoE-KO mice. CONCLUSIONS: This novel study is the first to reveal that a deficiency in ApoE impairs gastric motility functions, and that hyperlipidemia and the suppression of selective antioxidants may be an underlying mechanism for this pathological change. PMID- 22302248 TI - One IVIG mystery solved, another demands vigilance. PMID- 22302247 TI - Long-term blood pressure control: is there a set-point in the brain? AB - Mean arterial pressure fluctuates depending on physical or psychological activity, but should be stable at rest at around 100 mmHg throughout an entire life in human. The causes of hypertension and the blood pressure regulation mechanisms have been discussed for a long time, and many aspects have recently become more clear. Circulatory shock or short-term hypotension can be treated based on what is now known, but chronic hypertension is still difficult to treat thoroughly. The exact mechanisms for long-term blood pressure regulation have yet not been elucidated. Neuro-humoral interaction has been suggested as one of the mechanisms. Then, from the 1990s, paracrine hormones like nitric oxide or endothelins have been extensively researched in order to develop endothelial local control mechanisms for blood pressure, which have some relationships to long-term control. Although these new ideas and mechanisms are newly developed, no clear explanation for long-term control has yet been discussed, except for renal abnormality. Recently, a central set-point theory has begun to be discussed. This review will discuss the mechanisms for long-term blood pressure control, based on putative biological missions of circulatory function for life support. PMID- 22302249 TI - Medication guides leave their REMS programs behind. PMID- 22302250 TI - Remote technician supervision up and running in Kansas. PMID- 22302251 TI - Using integrated learning modules to increase involvement in ASHP student society. PMID- 22302252 TI - Development and implementation of a clinical pharmacist training and assessment program. PMID- 22302253 TI - Managing peak performers. PMID- 22302254 TI - Strategies to preserve the use of statins in patients with previous muscular adverse effects. AB - PURPOSE: The published evidence on strategies for avoiding the discontinuation of statin therapy due to muscular adverse effects is reviewed. SUMMARY: Statin medications are a cornerstone of the prevention and treatment of coronary heart disease, but about 20% of treated patients develop myalgia or other muscle related adverse effects that can lead to the discontinuation of statin use. As there are no consensus guidelines or firm practice recommendations on continuing or reinitiating statin therapy in patients who experience statin-related muscular adverse effects, a literature search was conducted to evaluate a variety of strategies that have been studied. The search results indicated that the most widely used strategies are (1) alternative statin dosing, (2) co-enzyme Q10 supplementation, (3) vitamin D supplementation, (4) conversion to red yeast rice (RYR) therapy, and (5) conversion to a different statin. While positive results in some patients have been reported with all of the strategies reviewed, the available evidence is insufficient to support the routine use of any of the strategies in clinical practice. In particular, the use of RYR, which contains a naturally occurring statin, is not recommended due to limited and inconsistent study results and uncertainty about the contents of commercially available RYR products. CONCLUSION: In patients intolerant to statin therapy due to myalgia or other muscular adverse effects, strategies such as alternative statin dosing schedules, coenzyme Q10 or vitamin D supplementation, and conversion to RYR or an alternative statin may allow some patients to continue to receive the benefits of lipid-lowering therapy. PMID- 22302255 TI - Persistent elevation of peripheral blood myeloid cell counts associated with omalizumab therapy. AB - PURPOSE: A case of persistent hematologic abnormalities in a patient receiving long-term omalizumab therapy for severe asthma is reported. SUMMARY: During the course of her treatment at an asthma clinic, a 24-year-old woman was noted to have increased white blood cell counts, with elevated myeloid cell counts; the blood abnormalities were first documented more than 12 months previously. The woman had been taking omalizumab for more than 2 years and was also receiving immune globulin therapy for common variable immunodeficiency. Based on the results of bone marrow aspiration and biopsy, she was diagnosed as having mild neutrophilia, possibly related to past corticosteroid therapy, but there was no evidence of a malignancy, a hemophagocytic syndrome, or an infectious, myeloproliferative, or lymphoproliferative process. Pursuant to a multidisciplinary medication review, the use of omalizumab was identified as a potential factor in the myeloid cell elevations and discontinued. About 1 month after omalizumab therapy was halted, the patient's myeloid cell counts normalized. The temporal association of omalizumab use and blood abnormalities in this case, coupled with the lack of data on the drug's long-term hematologic effects, suggests a need for cautious use and close monitoring of omalizumab therapy, particularly in younger patients. CONCLUSION: A patient with asthma and common variable immunodeficiency developed an elevation of peripheral blood myeloid cells that was first noticed 29 months after the initiation of monthly omalizumab injections. Omalizumab was discontinued, and the abnormality persisted for 1 month after the last dose. The patient's blood count results remained within normal limits 3 months after the last dose. PMID- 22302256 TI - Comparison of rates of reported adverse events associated with i.v. iron products in the United States. AB - PURPOSE: An analysis of reported adverse events (AEs) among patients using i.v. iron products, including the newer agent ferumoxytol, is presented. METHODS: All AE reports to the Food and Drug Administration (FDA) citing iron sucrose, ferric gluconate, high- and low-molecular-weight iron dextran products, or ferumoxytol from October 2009 through June 2010 were evaluated. The rates of various classifications of reported AEs were calculated on a per-unit-sold basis and, for comparison of products supplied in different unit sizes, also in terms of 100-mg dose equivalents (DEq) of iron. RESULTS: A total of 197 reported AEs were identified (a cumulative rate of 14.1 AEs per million units sold). The rates of all AE classifications combined ranged from 5.25 to 746 per million units sold for iron sucrose and ferumoxytol, respectively; using the other method of calculation, the rates ranged from 5.24 per million DEq (iron sucrose) to 147 per million DEq (ferumoxytol). Relative to iron sucrose and sodium ferric gluconate, ferumoxytol was associated with significantly elevated risks of death (odds ratio [OR], 475 and 156, respectively; p < 0.0001), serious nonfatal AEs (OR, 263 and 121, respectively; p < 0.0001), and all evaluated AE classifications combined (OR, 142 and 109, respectively; p < 0.05). CONCLUSION: Analysis of reports submitted to FDA revealed large differences among i.v. iron products in reported deaths, serious AEs, other major AEs, and other AEs. Iron sucrose and sodium ferric gluconate were associated with much lower rates of AEs per million units sold than iron dextran or ferumoxytol, which were associated with the highest rates of all reported AE classifications. PMID- 22302257 TI - Monitoring adverse drug reactions across a nationwide health care system using information technology. AB - PURPOSE: The improvement and linkage of two Department of Veterans Affairs (VA) databases for monitoring adverse drug reactions (ADRs) are described, with a discussion of the potential implications for improved medication safety within the VA health care system. SUMMARY: Before 2007, VA had limited capability to track and evaluate ADRs across its nationwide network of health care facilities. Since then, VA has established a standardized monitoring system that has improved the reporting, analysis, and trending of ADRs reported by providers and pharmacists at individual VA facilities. The enhanced system has two components with distinct but complementary functions: the Adverse Reaction Tracking database, which is derived by extracting text-based, patient-specific information entered into the VA electronic medical record system by clinicians at the point of care; and the VA Adverse Drug Event Reporting System (VA ADERS), an external web-based portal that contains aggregated data from 146 VA facilities, with standardized coding of reported events. Both databases allow for ADR reporting at the local, regional, and national levels. The VA ADERS database permits rapid electronic reporting of certain ADRs to the federal MedWatch program. The two databases can be used in tandem for more comprehensive assessments of ADR patterns and reporting rates and to generate a wide range of benchmarking data. CONCLUSION: In recent years, the refinement of two databases for ADR reporting has increased VA's capability to systematically monitor, track, and report ADRs across its national network of health care facilities. Linking the two databases has further strengthened those capabilities, enhancing medication safety practices and aiding in pharmacovigilance. PMID- 22302258 TI - Impact of atrial fibrillation and oral anticoagulation on hospital costs and length of stay. AB - PURPOSE: The results of a study assessing hospital length of stay (LOS) and inpatient costs associated with nonvalvular atrial fibrillation (AF) and AF related warfarin use during hospitalization are presented. METHODS: Managed care administrative claims data were used to construct cohorts of patients hospitalized with AF as a primary (n = 1,868) or secondary (n = 11,200) discharge diagnosis and control groups of patients with similar demographics and clinical characteristics who were hospitalized during the same period (2002-07). Multivariate regression analyses were performed to estimate the incremental impact of AF on hospital LOS and costs per admission, as well as the incremental impact of in hospital warfarin use on the evaluated LOS and cost outcomes. RESULTS: The cohort of patients with AF as a secondary discharge diagnosis had a mean LOS 1.84 days greater (p < 0.001) and a mean hospital costs $3,146 higher (p < 0.001) than the control cohort; in hospital warfarin use in those patients was associated with a mean increase in LOS of 1.45 days (p < 0.001) and a mean increase in hospital costs of $1,761 per admission (p < 0.001). In the cohort of patients with AF as a primary discharge diagnosis, inpatient warfarin therapy was also associated with longer hospital stays (mean increase, 1.26 days; p < 0.001) and higher hospital costs (mean increase, $678; p = 0.031). CONCLUSION: Hospitalizations of patients with a secondary diagnosis of AF are significantly longer and more costly than those of patients without a secondary diagnosis of AF, especially when warfarin is used during the hospital stay. Among patients with a primary diagnosis of AF, warfarin therapy during hospitalization is associated with significant increases in mean LOS and hospital costs. PMID- 22302259 TI - Evaluation of a transplantation specialty pharmacy program. AB - PURPOSE: The value of a transplantation specialty pharmacy (TSP) program, including its impact on patient and health care provider satisfaction, selected clinical outcomes, and the institution's financial margin, was evaluated. METHODS: Patient and health care provider surveys were distributed to evaluate satisfaction with the TSP program. Medication adherence (using continuous measures of medication adherence), hospital readmissions within 90 days of transplantation, and length of hospitalization were examined. Patients enrolled in the TSP program who received kidney transplants between July 1, 2009, and June 30, 2010, were included. Patients who received kidney transplants at the institution between July 1, 2007, and June 30, 2008, served as the control group. RESULTS: Of the 838 patient surveys distributed, 290 (34.6%) were returned. Most patients (84%) reported being satisfied with the program, and 98% would recommend it to others. Ninety-six percent of providers believed the pharmacy improved continuity of care, and 91% reported spending less time on pharmacy-related problems after the program's initiation. Medication adherence appeared to be higher in patients enrolled in the TSP program compared with historical controls. Hospital readmissions and length of stay did not significantly differ between groups. The TSP program generated $7.5 million in revenue during its first fiscal year. Roughly $5.5 million was spent on incremental operating expenses, resulting in over $2 million in margin. CONCLUSION: A TSP program provided a high level of satisfaction to patients and health care providers, may have influenced some clinical outcomes, and served as a source of positive margin for its institution. PMID- 22302260 TI - Pharmacy department not liable for use of contraindicated drug in surgical suite. PMID- 22302261 TI - The new era of APOL1-associated glomerulosclerosis. PMID- 22302262 TI - Salvage hepatectomy for local recurrent hepatocellular carcinoma after ablation therapy. AB - BACKGROUND: The results of salvage hepatectomy for local recurrent hepatocellular carcinoma after incomplete percutaneous ablation therapy are still unclear. METHODS: We conducted a retrospective analysis of 197 consecutive patients with hepatocellular carcinoma who underwent either salvage hepatectomy after prior incomplete percutaneous ablation therapy (salvage group; n=23) or primary hepatectomy as the initial treatment (primary group; n=174). The two groups were compared with respect to intraoperative data, operative mortality and morbidity, and long-term survival. RESULTS: The salvage group showed a significantly longer operation time (385 vs. 300 min; P=0.006) and a significantly greater intraoperative blood loss volume (402 vs. 265 ml; P=0.024). The postoperative mortality rate was zero in both groups, and the morbidity rates were similar. Although the 1-, 3-, and 5-year disease-free survival rates after hepatectomy were significantly worse in the salvage group than in the primary group (65%, 41%, and 33% vs. 81%, 51%, and 45%, respectively; P=0.031), the overall survival rates after hepatectomy did not differ significantly (91%, 91%, and 67% vs. 96%, 79%, and 65%, respectively; P=0.790). The 1-, 3-, and 5-year overall survival and disease-free survival rates after percutaneous ablation therapy were also not different from those in the primary group (100, 96, and 83%, P=0.115; and 96, 60, and 45%, P=0.524, respectively). CONCLUSIONS: The short-term and long-term results of salvage hepatectomy after incomplete percutaneous ablation therapy are equivalent to those of primary hepatectomy. Salvage hepatectomy is an acceptable treatment for patients with local recurrence of hepatocellular carcinoma after ablation therapy. PMID- 22302263 TI - The relationship of lymph node evaluation and colorectal cancer survival after curative resection: a multi-institutional study. AB - BACKGROUND: Esophagectomy remains the mainstay treatment for clinical T1bN0M0 esophageal cancer because pathologic lymph node metastases in these patients are not negligible. Recently, chemoradiotherapy (CRT), which can preserve the esophagus, has been reported to be a promising therapeutic alternative to esophagectomy. However, to our knowledge, no comparative studies of esophagectomy and CRT have been reported in clinical T1bN0M0 esophageal cancer. METHODS: A total of 173 patients with clinical T1bN0M0 squamous cell carcinoma of the thoracic esophagus were enrolled in this study, 102 of whom were treated with radical esophagectomy (S group) and 71 with definitive CRT (CRT group). Treatment results of both groups were retrospectively compared. RESULTS: No statistically significant difference was found in overall survival, but the S group displayed significantly better progression-free survival than the CRT group. Disease recurrence was observed in 12 S group patients and 20 CRT group patients. The incidence of distant recurrence was similar, while local recurrence and lymph node recurrence were significantly more frequent in the CRT group. In the S group, 20 patients had pathologic lymph node metastasis. The progression-free survival of patients with pathologic lymph node metastasis did not differ from those without nodal metastasis. In the CRT group, local recurrence could be controlled by salvage esophagectomy, but treatment results of lymph node recurrence were poor; only 4 of 12 patients with lymph node recurrences were cured. CONCLUSIONS: Selection of patients at high risk of pathologic lymph node metastasis is essential when formulating treatment decisions for clinical T1bN0M0 esophageal cancers. PMID- 22302264 TI - Comparison between radical esophagectomy and definitive chemoradiotherapy in patients with clinical T1bN0M0 esophageal cancer. AB - BACKGROUND: Esophagectomy remains the mainstay treatment for clinical T1bN0M0 esophageal cancer because pathologic lymph node metastases in these patients are not negligible. Recently, chemoradiotherapy (CRT), which can preserve the esophagus, has been reported to be a promising therapeutic alternative to esophagectomy. However, to our knowledge, no comparative studies of esophagectomy and CRT have been reported in clinical T1bN0M0 esophageal cancer. METHODS: A total of 173 patients with clinical T1bN0M0 squamous cell carcinoma of the thoracic esophagus were enrolled in this study, 102 of whom were treated with radical esophagectomy (S group) and 71 with definitive CRT (CRT group). Treatment results of both groups were retrospectively compared. RESULTS: No statistically significant difference was found in overall survival, but the S group displayed significantly better progression-free survival than the CRT group. Disease recurrence was observed in 12 S group patients and 20 CRT group patients. The incidence of distant recurrence was similar, while local recurrence and lymph node recurrence were significantly more frequent in the CRT group. In the S group, 20 patients had pathologic lymph node metastasis. The progression-free survival of patients with pathologic lymph node metastasis did not differ from those without nodal metastasis. In the CRT group, local recurrence could be controlled by salvage esophagectomy, but treatment results of lymph node recurrence were poor; only 4 of 12 patients with lymph node recurrences were cured. CONCLUSIONS: Selection of patients at high risk of pathologic lymph node metastasis is essential when formulating treatment decisions for clinical T1bN0M0 esophageal cancers. PMID- 22302265 TI - Combined diffusion-weighted and gadolinium-enhanced MRI can accurately predict the peritoneal cancer index preoperatively in patients being considered for cytoreductive surgical procedures. AB - PURPOSE: To determine whether abdominal and pelvic magnetic resonance imaging (MRI) with diffusion-weighted and dynamic gadolinium-enhanced imaging can be used to accurately calculate the peritoneal cancer index (PCI) before surgery compared to the PCI tabulated at surgery. METHODS: Thirty-three patients underwent preoperative MRI followed by cytoreductive surgery for primary tumors of the appendix (n = 25), ovary (n = 5), colon (n = 2), and mesothelioma (n = 1). MRIs were retrospectively reviewed to determine the MRI PCI. These scores were then compared to PCI tabulated at surgery. Patients were categorized as having small volume tumors (PCI 0-9), moderate-volume tumors (PCI 10-20), and large-volume tumors (PCI > 20). The respective anatomic site scores for both MRI and surgery were compared. RESULTS: There was no significant difference between the MRI PCI and surgical PCI for the 33 patients (P = 0.12). MRI correctly predicted the PCI category in 29 (0.88) of 33 patients. Compared to surgical findings, MRI correctly predicted small-volume tumor in 6 of 7 patients, moderate-volume tumor in 3 of 4 patients, and large-volume tumor in 20 of 22 patients. MRI and surgical PCI scores were identical in 8 patients (24%). A difference of <5 was noted in 16 patients (49%) and of 5-10 in 9 patients (27%). Compared to surgical-site findings, MRI depicted 258 truly positive sites of peritoneal tumor, 35 falsely negative sites, 35 falsely positive sites, and 101 truly negative sites, with a corresponding sensitivity of 0.88, specificity of 0.74, and accuracy of 0.84. CONCLUSIONS: Combined diffusion-weighted and gadolinium-enhanced peritoneal MRI accurately predicts the PCI before surgery in patients undergoing evaluation for cytoreductive surgery. PMID- 22302266 TI - Cytoreductive surgery with selective versus complete parietal peritonectomy followed by hyperthermic intraperitoneal chemotherapy in patients with diffuse malignant peritoneal mesothelioma: a controlled study. AB - BACKGROUND: Combined treatment involving peritonectomy procedures, multivisceral resections, and hyperthermic intraperitoneal chemotherapy (HIPEC) has reportedly resulted in survival benefit for peritoneal surface malignancies, including diffuse malignant peritoneal mesothelioma (DMPM). Many unanswered questions remain regarding the surgical options in the management of DMPM. The aim of this case-control study was to assess the impact of the type and extent of parietal peritonectomy on survival and operative outcomes. METHODS: Thirty patients with DMPM undergoing selective parietal peritonectomy (SPP) of macroscopically involved regions, and 30 matched patients undergoing routine complete parietal peritonectomy (CPP), regardless of disease distribution, were retrospectively identified from a prospective database. RESULTS: Groups were comparable for all characteristics, except for a higher proportion of patients treated before July 2003 and undergoing preoperative systemic chemotherapy in the SPP group. Median follow-up was 86.2 months in the SPP group and 50.3 months in the CPP group. Median overall survival was 29.6 months in the SPP group and not reached in the CPP group; 5-year overall survival was 40.0% and 63.9%, respectively (P = 0.0269). At multivariate analysis, CPP versus SPP was recognized as an independent predictor of better prognosis, along with complete cytoreduction, negative lymph nodes, epithelial histology, and lower MIB-1 labelling index. Morbidity and reoperation rates were not different between groups. No operative mortality occurred. In 12 of 24 patients undergoing CPP, pathologic examination detected disease involvement on parietal surfaces with no evident tumor at surgical exploration. CONCLUSIONS: CPP improved survival in patients with DMPM undergoing combined treatment. This information may contribute to standardize surgical options for DMPM and other peritoneal malignancies. PMID- 22302267 TI - Importance of histologic subtype in the staging of appendiceal tumors. AB - BACKGROUND: Malignant neoplasms of the appendix have different behavior based on their histologic subtypes in anecdotal series. Current staging systems do not capture the diversity of histologic subtypes in predicting outcomes. METHODS: We queried all patients with appendiceal malignancies captured in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2007. Tumors were classified as colonic type adenocarcinoma, mucinous adenocarcinoma, signet ring cell type, goblet cell carcinoid, and malignant carcinoid. We compared incidence, overall survival, and disease-specific survival for these tumors on the basis of patient, tumor, and therapy characteristics. Estimates from Cox proportional hazard modeling were used to predict hazard ratios for differing histologic subtypes with similar tumor, node, metastasis system (TNM) stages. RESULTS: Of the 5672 patients identified, we included 5655 (99%) in our analysis. The 5-year disease-specific survival rates were 93% for malignant carcinoid, 81% for goblet cell carcinoid, 55% for colonic type adenocarcinoma, 58% for mucinous adenocarcinoma, and 27% for signet ring cell type. Predicted estimates of adjusted hazard ratios revealed an 8-fold difference between histologic subtypes for similar TNM stages. CONCLUSIONS: Histologic subtype is an important predictor of disease-specific survival and overall survival in patients with appendiceal neoplasms. Addition of the histologic subtype to the TNM staging is simple and may improve prognostication. PMID- 22302268 TI - Quality of life outcomes after isolated limb infusion. AB - BACKGROUND: Isolated limb infusion (ILI) for the treatment of in-transit melanoma was originally described more than 10 years ago. Response rates of 45-53% have been reported in U.S. series. Long-term quality of life outcomes after this procedure have not been described. We hypothesized that ILI is rarely associated with long-term limb morbidity. METHODS: ILIs performed at our institution between July 2005 and June 2009 were reviewed. Patients were contacted cross-sectionally at 2 time points. During these interviews, response to treatment and postoperative limb function were assessed. RESULTS: Thirty-two ILIs were performed during the time period. Twenty-seven patients were treated for in transit melanoma; 5 were treated for recurrent Merkel cell carcinoma. The 30-day mortality was 0%. Three patients (9%) required fasciotomy. Durable complete responses were achieved in 41% of patients, with mean follow-up time of 19.4 +/- 9.6 months after infusion; after this period, 53% reported progression of disease. The most common postprocedure symptoms were edema (88%), numbness (59%), and pain (59%). By 3 months and at the time of last follow-up, the most common symptoms were edema (82%), numbness (65%), and stiffness (35%). No patients reported impaired limb function at the time of last follow-up compared to baseline. Median survival was 19.2 +/- 4.2 months after infusion. CONCLUSIONS: ILI for melanoma and Merkel cell carcinoma is associated with postprocedure symptoms in most patients, most commonly edema, color change, and numbness. At last follow-up, no ILI patients had residual functional impairment in the treated limb. PMID- 22302269 TI - Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal sarcomatosis. AB - BACKGROUND: The prognosis of peritoneal sarcomatosis is generally poor and conventional treatments for this disease process are mostly ineffective. The use of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as an aggressive locoregional treatment option remains controversial. METHODS: We reviewed 13 patients with peritoneal sarcomatosis who underwent CRS and closed-abdomen HIPEC with cisplatin and doxorubicin between March 2007 and March 2010. None of the patients was diagnosed with GIST or uterine leiomyosarcoma. Both disease-free survival (DFS) and overall survival (OS) were evaluated. Completeness of cytoreduction (CC) and peritoneal cancer index (PCI) were assessed. RESULTS: There was no operative mortality. Median follow-up was 12 (range, 4-43) months. Peritoneal disease progression occurred in six patients, distant metastases alone in none, and both in two patients. Median DFS and OS were 11 and 12 months, respectively. Completeness of cytoreduction significantly affected survival. Mean DFS and OS in those patients where a CC-0 was achieved was 27.25 +/- 5.71 (median, 20) months and 35.25 +/- 4.75 months (median, not reached). In contrast, patients with gross residual disease (CC >= 1) had a DFS of 4.25 +/- 1.43 months (median, 4 months; P = 0.03) and an OS of 5.25 +/- 2.36 months (median, 4 months; P = 0.02). In addition, PCI influenced survival when evaluated by univariate analysis. Using multivariate analysis, completeness of cytoreduction was the only covariate influencing overall survival (P = 0.012). CONCLUSIONS: A complete cytoreduction and low PCI score appear to be important factors in considering CRS and HIPEC for patients with peritoneal sarcomatosis. PMID- 22302270 TI - Aggressive management of peritoneal carcinomatosis from mucinous appendiceal neoplasms. AB - BACKGROUND: Peritoneal carcinomatosis (PC) in the setting of mucinous appendiceal neoplasms is characterized by the intraperitoneal accumulation of mucinous ascites and mucin-secreting epithelial cells that leads to progressive compression of intra-abdominal organs, morbidity, and eventual death. We assessed postoperative and oncologic outcomes after aggressive surgical management by experienced surgeons. METHODS: We analyzed clinicopathologic, perioperative, and oncologic outcome data in 282 patients with PC from appendiceal adenocarcinomas between 2001 and 2010 from a prospective database. Kaplan-Meier survival curves and multivariate Cox-regression models were used to identify prognostic factors affecting oncologic outcomes. RESULTS: Adequate cytoreduction was achieved in 82% of patients (completeness of cytoreduction score (CC)-0: 49%; CC-1: 33%). Median simplified peritoneal cancer index (SPCI), operative time, and estimated blood loss were 14 (range, 0-21), 483.5 min (range, 46-1,402), and 800 ml (range, 0 14,000), respectively. Pathology assessment demonstrated high-grade tumors in 36% of patients and lymph node involvement in 23% of patients. Major postoperative morbidity occurred in 70 (25%) patients. Median overall survival was 6.72 years (95% confidence interval (CI), 4.17 years not reached), with 5 year overall survival probability of 52.7% (95% CI, 42.4, 62%). In a multivariate Cox regression model, tumor grade, age, preoperative SPCI and chemo-naive status at surgery were joint significant predictors of overall survival. Tumor grade, postoperative CC-score, prior chemotherapy, and preoperative SPCI were joint significant predictors of time to progression. CONCLUSIONS: Aggressive management of PC from mucinous appendiceal neoplasms, by experienced surgeons, to achieve complete cytoreduction provides long-term survival with low major morbidity. PMID- 22302271 TI - Chronic anti-inflammatory drug therapy inhibits gel-forming mucin production in a murine xenograft model of human pseudomyxoma peritonei. AB - BACKGROUND: Intraperitoneal accumulation of mucinous ascites in pseudomyxoma peritonei (PMP) promotes an inflammatory/fibrotic reaction that progresses to bowel obstruction and eventual patient demise. Cytokines and inflammation associated transcription factor binding sites, such as glucocorticoid response elements and COX-2, regulate secretory mucin, specifically MUC2, production. We hypothesized that anti-inflammatory drugs targeting inflammation-associated pathways may reduce mucin production and subsequent disease morbidity in PMP. METHODS: The effects of dexamethasone and Celebrex were assessed in mucin secreting human colon cancer LS174T cells in vitro and murine xenograft models of LS174T and human appendiceal PMP in vivo by serial parametric measurements, MUC2 transcripts via real-time RT-PCR, and MUC2 protein expression via immunofluorescence assays. RESULTS: Dexamethasone significantly inhibited basal MUC2 mRNA levels in LS174T cells, inhibited mucinous tumor accumulation in an intraperitoneal PMP xenograft model, and prolonged survival in a subcutaneous LS174T xenograft model. Celebrex significantly inhibited sodium butyrate stimulated MUC2 mRNA levels in LS174T cells and demonstrated a statistically nonsignificant trend toward reduced mucinous tumor growth and prolonged survival in the xenograft models. MUC2 protein analysis by immunofluorescence demonstrated a dual effect of dexamethasone on mucin production and tumor cell count. CONCLUSIONS: Inflammatory mediators are known to regulate mucin production and may promote overexpression of MUC2 by neoplastic cells with goblet cell phenotype in PMP. Anti-inflammatory drugs, dexamethasone and Celebrex, could inhibit extracellular mucin production in PMP by targeting inflammatory cascades and, therefore, may decrease compressive symptoms, increase the disease-free interval, and reduce the extent or frequency of morbid cytoreductive surgeries. PMID- 22302272 TI - Concepts of regional therapies for advanced malignancy. PMID- 22302274 TI - Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort. AB - The hereditary sensory and autonomic neuropathies (HSAN, also known as the hereditary sensory neuropathies) are a clinically and genetically heterogeneous group of disorders, characterised by a progressive sensory neuropathy often complicated by ulcers and amputations, with variable motor and autonomic involvement. To date, mutations in twelve genes have been identified as causing HSAN. To study the frequency of mutations in these genes and the associated phenotypes, we screened 140 index patients in our inherited neuropathy cohort with a clinical diagnosis of HSAN for mutations in the coding regions of SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 (TRKA) and NGFB. We identified 25 index patients with mutations in six genes associated with HSAN (SPTLC1, RAB7, WNK1/HSN2, FAM134B, NTRK1 and NGFB); 20 of which appear to be pathogenic giving an overall mutation frequency of 14.3%. Mutations in the known genes for HSAN are rare suggesting that further HSAN genes are yet to be identified. The p.Cys133Trp mutation in SPTLC1 is the most common cause of HSAN in the UK population and should be screened first in all patients with sporadic or autosomal dominant HSAN. PMID- 22302275 TI - Rhazes (865-925 AD). PMID- 22302276 TI - Migraine with aura in patients over 50 years of age: the Marseille's registry. AB - The goal of this study was to describe specifically the clinical characteristics of migraine with aura inpatients over the age of 50. During 1 year, three neurologists working in a tertiary headache center included all patients aged 50 years and over presenting migraine with aura in a prospective registry. Fifty seven patients with migraine with aura aged 50 years and over were interviewed using a standardized questionnaire during a consultation. Auras were visual for all the patients, paresthesic for 16 patients, and aphasic for 16. One patient had a sporadic hemiplegic migraine. The headache followed the aura in a large majority of patients and fulfilled the International Headache Society criteria for migraine headache for 38 patients. Typical aura without headache was described in 26 patients and was the only expression of the disease for five patients. Two groups can be defined: in the first one, migraine with aura began before 50 years (39 patients). Thirty-one patients had typical aura with migraine headache and 15 complained of typical aura without headache. The second group (18 patients) included patients who developed migraine with aura over 50 for the first time. Among them, patients may have typical aura with migraine headache (seven patients), typical aura with non-migraine headache (eight patients) and/or typical aura without headache (11 patients). Late-life onset transient visual phenomena are not rare. These symptoms may occur for the first time after 50, in the absence of headache. When migraine with aura began after 50 years, headache has more often the characteristics of typical aura with nonmigraine headache, or migraine may have the presentation of typical migraine without headache. PMID- 22302277 TI - Quantitative assessment of visual behavior in disorders of consciousness. AB - The study of eye behavior is of paramount importance in the differential diagnosis of disorders of consciousness (DoC). In spite of this, assessment of eye movement patterns in patients with vegetative state (VS) or minimally conscious state (MCS) only relies on clinical evaluation. In this study we aimed to provide a quantitative assessment of visual tracking behavior in response to moving stimuli in DoC patients. Nine VS patients and nine MCS patients were recruited in a Neurorehabilitation Unit for patients with chronic DoC; 11 matched healthy subjects were tested as the control group. All participants under went a quantitative evaluation of eye-tracking pattern by means of a computerized infrared eye-tracker system; stimuli were represented by a red circle or a small color picture slowly moving on a PC monitor. The proportion of on- or off-target fixations differed significantly between MCS and VS. Most importantly, the distribution of fixations on or off the target in all VS patients was at or below the chance level, whereas in the MCS group seven out of nine patients showed a proportion of on-target fixations significantly higher than the chance level. Fixation length did not differ among the three groups significantly. The present quantitative assessment of visual behaviour in a tracking task demonstrated that MCS and VS patients differ in the proportion of on-target fixations. These results could have important clinical implications since the quantitative analysis of visual behavior might provide additional elements in the differential diagnosis of DoC. PMID- 22302279 TI - Indian sports nicknames/logos: affective difference between American Indian and non-Indian college students. AB - The use of American Indian (AI) words and images in athletic teams' nicknames, logos, and mascots remains a controversial issue. This study investigated the emotional impact of the University of North Dakota's "Fighting Sioux" nickname/logo on 33 AI and 36 majority culture (MC) students enrolled at the university. Participants completed the Multiple Affect Adjective Checklist Revised (MAACL-R) before viewing two slide presentations of Fighting Sioux related images: one neutral (i.e., non-controversial) and one controversial. Participants completed the MAACL-R after each presentation. They also completed the Nickname and Logo Distress Scale, and AI participants completed the Northern Plains Biculturalism Inventory to assess their degree of cultural orientation. Results showed that AIs experienced higher negative affect following both slide presentations than did MC participants. MC participants' affect was only changed following the controversial slide presentation. The findings suggest AI students may experience significantly higher levels of psychological distress when viewing even neutral images of AI nicknames/logos. PMID- 22302278 TI - Automated external defibrillators and secondary prevention of sudden cardiac death among children and adolescents. AB - Sudden cardiac death is devastating at any age, but it is especially so among children and adolescents. This report discusses the outcomes for patients with out-of hospital cardiac arrest (OHCA) and describes public access defibrillation programs in general and those directed at children and adolescents. In addition, the relatively new concept of cardiopulmonary resuscitation (CPR)-automated external defibrillator (AED) programs directed at schools is discussed. Although limited data are available, some of the preliminary data suggest improved OHCA outcomes associated with CPR-AED programs implemented in schools. These early data provide hope for the future potential reduction in the incidence of sudden cardiac deaths in the school setting, not only among children and adolescents, but also among adults. PMID- 22302280 TI - "It runs in the family": intergenerational transmission of historical trauma among urban American Indians and Alaska Natives in culturally specific sobriety maintenance programs. AB - The aim of this exploratory study, which was informed by ethnographic principles, was to better understand the intergenerational transmission of historical trauma among urban American Indians/Alaska Natives (AI/ANs) in culturally specific sobriety maintenance programs. The results of the study were organized into 3 overarching categories, which included 10 themes that emerged contextually in relation to participants' lived experience of historical and associated traumas, substance abuse, and current involvement in a culturally specific sobriety maintenance program. PMID- 22302281 TI - Chokka-Chaffa' Kilimpi', Chikashshiyaakni' Kilimpi': strong family, strong nation. AB - To encourage the health and well-being of American Indian (AI) communities, it is first necessary to understand the meaning of health for particular tribes. As such, this investigation reports on the meaning of health and well-being for Chickasaw families. Findings from this investigation additionally highlight ways in which characteristics of strong Chickasaw families are both similar to and different from those of other AI tribes. Implications for science and practice are discussed. PMID- 22302282 TI - Outcome following management of dysphagia after laparoscopic anti-reflux surgery. AB - BACKGROUND: Some patients develop troublesome dysphagia after laparoscopic antireflux surgery, and a proportion require further intervention. The management of this problem was evaluated. METHODS: Patients who underwent intervention for dysphagia after laparoscopic fundoplication were identified from a database. Outcomes were prospectively determined from a standardized questionnaire that evaluated symptoms scores for dysphagia for solids and liquids, as well as patient satisfaction with the overall outcome. Outcomes 1 year after reintervention, and at the most recent follow-up were evaluated. RESULTS: From 1994 to 2009, 121 (6.6%) of 1,821 patients who underwent laparoscopic fundoplication for gastroesophageal reflux also underwent endoscopic or surgical reintervention for dysphagia. Of these 121 patients, 56 underwent endoscopic dilatation, and 24 were satisfied with the outcome of dilatation; 18 progressed to surgery, and dysphagia persisted in 14 of them. Overall, 83 patients underwent revisional surgery, and 47 (62.7%) were satisfied with the outcome. Compared to patients who did not undergo any intervention for dysphagia, patients who underwent reintervention had lower satisfaction scores and higher dysphagia scores. CONCLUSIONS: Approximately two thirds of patients with troublesome post fundoplication dysphagia have a satisfactory outcome following either endoscopic dilatation or revisional surgery. However, approximately one third continue to be troubled by symptoms, despite further intervention. PMID- 22302283 TI - Video-assisted versus conventional total thyroidectomy and central compartment neck dissection for papillary thyroid carcinoma. AB - BACKGROUND: Although video-assisted (VA) thyroidectomy emerged as effective treatment for selected patients with papillary thyroid carcinoma (PTC), some concerns remain about obtaining adequate central neck node clearance. We compared patients who underwent VA and conventional total thyroidectomy (TT) and central compartment dissection (CCD) for PTC. METHODS: A total of 52 consecutive patients successfully underwent VA-TT and VA-CCD for PTC (VA group) were compared to 52 controls who underwent conventional TT and CCD (C group) for PTC. RESULTS: The two groups were matched for age (p = 0.75), sex (p = 0.07), and tumor size (p = 1.0). Operating time (p = 0.23), overall postoperative complications (p = 0.41), pT (p = 0.44), and pN (p = 0.84) were similar in the two groups. The mean number of removed nodes was similar (10.6 +/- 4.6 in VA group vs. 12.2 +/- 5.6 in C group) (p = 0.11).Mean postoperative serum thyroglobulin (sTg) off levothyroxine (LT4) suppressive treatment was 3.2 +/- 5.0 ng/ ml in the VA group and 2.6 +/- 7.4 ng/ml in the C-group (P = 0.67). Mean postoperative radioiodine uptake (RAIU) was similar in the two groups (1.5 +/- 1.3 vs. 1.7 +/- 1.3%) (p = 0.49). When pN1a patients alone were considered, no difference was found between the VA group (21 patients) and the controls (24 patients) concerning the mean number of removed nodes (10.3 +/- 4.1 vs. 12.4 +/- 5.6) (p = 0.16), the mean sTg off LT4 (4.4 +/- 6.0 vs. 1.9 +/- 2.7 ng/ml) (p = 0.07) and the mean RAIU (1.9 +/- 1.5 vs. 1.7% +/- 1.3%) (p = 0.63). CONCLUSIONS: The results of VA-TT and CCD in selected cases of PTC appear to be comparable to those of conventional surgery. A longer follow-up and larger series are necessary to draw definitive conclusions concerning longterm outcomes. PMID- 22302284 TI - Clinicopathological profile, airway management, and outcome in huge multinodular goiters: an institutional experience from an endemic goiter region. AB - BACKGROUND: Huge goiters are common in iodine-deficient endemic regions. They are of concern to the surgeons because of the anticipated risk of difficult dissection and increased chances of surgical complications. Similarly, they are of concern to the anesthesiologists because of anticipated intubation-related difficulties and post-thyroidectomy tracheomalacia. In the present study we aimed to present our experience of managing goiters based on their gross weight, highlighting their clinicopathological profile, perioperative airway-related difficulties, and management of surgical morbidity. METHODS: Retrospective analysis of patients who underwent total thyroidectomy in the primary setting at our institute from 1995 to 2009 was carried out based on the gross gland weight. The patients were thus grouped into group A: <=200 g; group B: 201 to <=400 g; group C: 401 to <=600 g; group D: >600 g. RESULTS: Group A (660 cases); group B (108 cases); group C (36 cases); and group D (9 cases) were included. As the goiter size increased, the mean duration of goiter, compressive symptoms, retrosternal extension (RSE), airway deformity, intubation difficulty, and tracheomalacia increased. The rate of tracheostomy, sternotomy, hemorrhage, visceral injury, and hospital stay was high with huge goiters. These features were more marked in malignant goiters compared to benign goiters. However, the postoperative complications were comparable in both of those groups. CONCLUSIONS: Long-standing huge goiters are common in iodine-deficient endemic areas. The majority of patients have symptomatic or clinicoradiological evidence of airway involvement. The incidence of RSE, airway deformity, intubation difficulty, and tracheomalacia is high with huge goiters. The surgery is technically demanding with greater associated chances of injury to native structures. Malignancy influences the presentation and outcome in smaller goiters. In centers with experienced endocrine surgeons and dedicated anesthetists, huge goiters can be successfully managed with minimal short-term and long-term morbidity. PMID- 22302285 TI - Adjuvant vaccination with melanoma antigen-pulsed dendritic cells in stage III melanoma patients. AB - Dendritic cells may be successfully used to induce in vivo-specific anti-tumor responses when combined with the appropriate antigen in the appropriate context. The purpose of this study was to evaluate efficacy of peptide-loaded DC vaccine in high-risk stage III melanoma patients after lymph node dissection (LND). HLA A2+, -A1+, or -A3+ melanoma patients (N=22), stage III, N1b-N3, received 5-16 (median: 11) DC vaccines loaded with MHC class-I-restricted melanoma peptides respective to the patient's haplotype, and with autologous tumor lysate, if available. Vaccinated patients were matched to unvaccinated stage III controls (22 of 869) by sex, number of metastatic lymph nodes, extracapsular involvement, LND type, Breslow stage, and ulceration. Vaccination elicited cutaneous delayed type hypersensitivity (DTH) or/and IFN-gamma-producing CD8+ cell response to melanoma peptides in 15 of 22 patients. Three-year overall survival (OS) rate was 68.2% in the vaccinated group versus 25.7% in the control group, P value accounting for matching: 0.0290. In a Cox regression model, hazard ratio (HR) for death of vaccinated patients was 0.31 [95% confidence interval (CI): 0.10-0.94]. The corresponding values for 3-year disease-free survival rate were 40.9 versus 14.5%, P=0.1083; HR of recurrence for vaccinated, 0.46 (95% CI: 0.18-1.22). There was no grade>1 toxicity. The DC/peptide vaccine was well tolerated and elicited immune responses to melanoma antigens. Vaccinated patients had significantly longer OS after LND than the matched controls, but a significant improvement in the primary endpoint DFS was not achieved. PMID- 22302286 TI - Correlation of LAPTM4B polymorphisms with gallbladder carcinoma susceptibility in Chinese patients. AB - Gallbladder carcinoma (GBC) is a malignancy with an extremely poor prognosis. In order to improve the survival rate, identification of new susceptibility risk factors is of importance. Here, we report findings on the novel cancer-related gene lysosomal protein transmembrane 4 beta (LAPTM4B) that has two alleles designated LAPTM4B*1 and LAPTM4B*2. Allele *1 differs from allele *2 in that it contains one copy of a 19-bp sequence, whereas this sequence is duplicated in exon 1 of allele *2. This study aimed to investigate the relationship of LAPTM4B allelic variation and GBC susceptibility. LAPTM4B genotype was analyzed in 155 healthy individuals and 91 GBC patients by PCR, and the genotypic distribution of LAPTM4B was analyzed with the chi-squared test. The frequency of allele *2 was 37.9 and 24.8% in the GBC and the control groups, respectively, representing a significant difference between these two groups (P<0.001). LAPTM4B allele *2 may be a risk factor associated with genetic susceptibility to GBC. PMID- 22302287 TI - Development of a novel real-time PCR-based strategy for simple and rapid molecular pathotyping of Newcastle disease virus. AB - A novel real-time PCR strategy was applied to simultaneously detect and to discriminate low-pathogenic lentogenic and virulent meso/velogenic Newcastle disease virus (NDV). The pathotyping is achieved by a three-step semi-nested PCR. A pre-amplification of the cleavage site (CS) region of the F gene is followed by a two-level duplex real-time PCR directly targeting the CS, combining detection and pathotyping in a single tube. A wide range of NDV isolates spanning all genotypes were successfully detected and pathotyped. Clinical samples from outbreaks in Sweden in 2010 that were positive by the novel PCR method were also successfully pathotyped. The method is time-saving, reduces labour and costs and provides opportunities for rapid diagnosis at remote locations and in the field. Since the same strategy was also recently applied to avian influenza virus pathotyping, it shows promise of finding broad utility in diagnostics of infectious diseases caused by different RNA viruses in various hosts. PMID- 22302288 TI - Characterization of Epstein-Barr virus type 1 nuclear antigen 3C sequence patterns of nasopharyngeal and gastric carcinomas in northern China. AB - Epstein-Barr virus nuclear antigen protein 3C (EBNA3C) is a 992-amino-acid protein that has been shown to play a complex regulatory role in the transcription of viral and cellular genes. In this study, we successfully amplified 26 Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs), 50 nasopharyngeal carcinomas (NPCs) and 27 throat washing (TW) samples from healthy donors. Based on a phylogenetic tree, the samples could be divided into three patterns. 3C-6 was the predominant subtype in northern China, and the variations between the strains sequenced in our study and those from southern China and Japan were similar, but differences were also identified. The distribution of EBNA3C subtypes among EBVaGCs, NPCs and healthy donors was not significantly different. These data suggest that EBNA3C gene variations are geographically restricted rather than tumor-specific polymorphisms. PMID- 22302289 TI - Stat3 is involved in the motility, metastasis and prognosis in lingual squamous cell carcinoma. AB - The signal transducers and activators of transcription 3 (Stat3) has been detected in many types of cancer and plays an important role in tumour-cell survival, proliferation, self-renewal and invasion. To address the possibility that Stat3 may be involved in the metastasis and prognosis in lingual squamous cell carcinoma, we examined whether Stat3 expression associates with metastasis or survival rate in human clinical samples. We found that there was a significant correlation between Stat3 expression and lymph node metastasis (P=0.009), stages (P=0.029), recurrence (P=0.0032) and death (P=0.0356). The specific knockdown of Stat3 by RNA interference strongly inhibited the motile and invasion activity of tumour cells. Our results suggest that Stat3 is involved in the motility, metastasis and progression in human lingual squamous cell carcinoma, and thus, it may be a therapeutic target for human lingual squamous cell carcinoma. PMID- 22302290 TI - Compliant silver nanowire-polymer composite electrodes for bistable large strain actuation. AB - A new compliant electrode-based on silver nanowire-polymer composite has been developed. The composite electrode has low sheet resistance (as low as 10 Omega/sq), remains conductive (10(2) -10(3) Omega/sq) at strains as high as 140%, and can support Joule heating. The combination of the composite and a bistable electroactive polymer produces electrically-induced, large-strain actuation and relaxation, reversibly without the need of mechanical programming. PMID- 22302291 TI - The pathogenesis of early retinal changes of diabetic retinopathy. AB - Recent successful trials of antibodies to vascular endothelial growth factor (VEGF) in diabetic retinopathy implicate this cytokine as a major cause of diabetic retinopathy (DR) and diabetic macular oedema (DME). The mechanisms which cause VEGF to be over-expressed to cause the vasculopathy are not entirely clear. This review explores the earliest changes to the retina in DR and the factors that predispose or prevent DR, including sleep apnoea, receptor degenerations laser treatment and VEGF polymorphism. The review also presents the evidence that retinal hypoxia, existing in the earliest stages, causes DR. This hypoxia is much increased by dark adaptation, indicating a new and possibly superior therapy. PMID- 22302293 TI - Fused 99m-Tc-GSA SPECT/CT imaging for the preoperative evaluation of postoperative liver function: can the liver uptake index predict postoperative hepatic functional reserve? AB - PURPOSE: To evaluate the role of hepatic asialoglycoprotein receptor analysis in the preoperative estimation of postoperative hepatic functional reserve. METHODS: We obtained technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin (99mTc-GSA) SPECT/CT fusion images in 256 patients with liver disease scheduled for hepatic resection. The liver uptake value corrected for body surface area [LUV(BSA)] and liver uptake ratio (LUR) of the remnant were preoperatively estimated based on the fused images. These values were compared with the postoperative hepatic functional reserve. RESULTS: Significant correlations were observed between LUV(BSA), LUR, and most conventional indicators of hepatic functional reserve. Postoperatively, nonpreserved liver functional reserve was observed in 15 of the 256 patients (5.8%). Remnant LUV(BSA) showed better correlation than remnant LUR or the other indicators. No patients with remnant LUV(BSA) above 28.0 manifested poor nonpreserved functional reserve. Using a LUV(BSA) of 27.0, it was possible to predict postoperative poor hepatic functional reserve at a sensitivity of 91%, specificity of 81%, and accuracy of 81% postoperatively. According to multivariate analysis, a low remnant LUV(BSA) was the only significant independent predictor of poor hepatic functional reserve. CONCLUSIONS: Our 99mTc-GSA SPECT/CT fusion imaging method was clinically useful for evaluating regional hepatic function and for predicting postoperative hepatic functional reserve. PMID- 22302294 TI - Efficacy of prophylactic single-dose therapy using fluoroquinolone for prostate brachytherapy. AB - PURPOSE: There is little definitive evidence to guide the use of prophylactic antibiotics for prostate brachytherapy. The purpose of this study is to evaluate the incidence of postimplant infections in patients who receive antimicrobial prophylaxis with pazufloxacin (PZFX). MATERIALS AND METHODS: A total of 84 patients who underwent prostate brachytherapy received a single intravenous dose of PZFX at 500 mg perioperatively for 1 day. No postimplant antibiotic medication was prescribed. Urinalysis, plasma white blood cell (WBC) count, and C reactive protein (CRP) levels were evaluated before the implantation, on the day after implantation, and on the 7th and 28th days after brachytherapy. RESULTS: None of the 84 patients (0.0%) developed a symptomatic urinary tract infection or had febrile infectious complications after brachytherapy. There were statistically significant elevations in the levels of erythrocytes, leukocytes, bacteria in urine, plasma WBC and CRP postoperatively, but these values did not exceed the normal range or were only slightly elevated on the day after brachytherapy (day 1) and on day 7. All laboratory examinations had returned to the normal range on day 28. CONCLUSION: Single-dose therapy with fluoroquinolone helps to prevent infections after prostate brachytherapy. PMID- 22302295 TI - Loss of cellular viability in areas of ground-glass opacity on computed tomography images immediately after pulmonary radiofrequency ablation in rabbits. AB - PURPOSE: To determine cellular viability of lung parenchyma and neoplastic cells in areas of ground-glass opacity (GGO) on computed tomography (CT) images immediately after pulmonary radiofrequency ablation (RFA) in rabbits. MATERIALS AND METHODS: A LeVeen RFA electrode was placed percutaneously into rabbit lungs with or without metastatic VX2 tumors. Five minutes later, seven isolated lungs were imaged by use of a multi-detector row CT scanner, and the images were compared with histological features. The cellular viability of the lung tissues was assessed by nicotinamide adenine dinucleotide hydrogen (NADH) staining in eight normal lungs and in three lungs with multiple metastatic tumors. RESULTS: All lung lesions appeared as bilayered structures with a central, dense, attenuated area and an outer area of GGO on CT images, and as three-layered structures on macroscopic and microscopic images 5 min after RFA. The GGO areas approximately corresponded to the outer two layers in macroscopic images that were exudative and congestive on microscopic images. Staining for NADH was significantly reduced in the GGO and densely attenuated areas with or without tumor tissue staining compared with the non-ablated area. CONCLUSIONS: Our results suggest that an area of GGO that appears on CT immediately after RFA can be effectively treated by RFA. PMID- 22302296 TI - Direct vasodilation by transdermal administration of nitroglycerin: preliminary, randomized, placebo-controlled trial of nitroglycerin skin spray for premedication before artery puncture. AB - PURPOSE: Transdermal administration of nitroglycerin (NTG) before arterial puncture may improve puncture success. The objective of this study was to evaluate the vasodilation effect of NTG skin spray on brachial arteries. MATERIALS AND METHODS: We recruited 10 healthy volunteers. On different days and in random order we sprayed their skin above the right or left brachial artery with a solution containing 0.3 mg NTG or above the right brachial artery with physiological saline. A radiologist ultrasonographically measured the cross sectional area of right brachial artery before and at 5-min intervals for up to 25 min after spraying and calculated the rate of increase of the area. RESULTS: The average vasodilation rate after spraying with NTG above the right brachial arteries of 10 volunteers was 16.4% at 5 min, 23.6% at 10 min, 19.6% at 15 min, and 16.5% at 20 min; spraying with NTG above the left brachial artery or with physiological saline alone elicited few changes. The vasodilation rate 10 min after spraying with NTG above the right brachial artery was significantly higher than for control groups (P < 0.001). CONCLUSIONS: Transdermal application of NTG spray dilated the targeted brachial artery. This technique may be a good premedication before artery puncture. PMID- 22302297 TI - Exercise pathophysiology in patients with chronic mountain sickness exercise in chronic mountain sickness. AB - BACKGROUND: Chronic mountain sickness (CMS) is characterized by a combination of excessive erythrocytosis,severe hypoxemia, and pulmonary hypertension, all of which affect exercise capacity. METHODS: Thirteen patients with CMS and 15 healthy highlander and 15 newcomer lowlander control subjects were investigated at an altitude of 4,350 m (Cerro de Pasco, Peru). All of them underwent measurements of diffusing capacity of lung for nitric oxide and carbon monoxide at rest, echocardiography for estimation of mean pulmonary arterial pressure and cardiac output at rest and at exercise, and an incremental cycle ergometer cardiopulmonary exercise test. RESULTS: The patients with CMS, the healthy highlanders, and the newcomer lowlanders reached a similar maximal oxygen uptake at 32 1, 32 2, and 33 2 mL/min/kg, respectively, mean SE( P 5 .8), with ventilatory equivalents for C O 2 vs end-tidal P CO 2 , measured at the anaerobic threshold,of 0.9 0.1, 1.2 0.1, and 1.4 0.1 mm Hg, respectively ( P , .001); arterial oxygen content of 26 1, 21 2, and 16 1 mL/dL, respectively ( P , .001); diffusing capacity for carbon monoxide corrected for alveolar volume of 155% 4%, 150% 5%, and 120% 3% predicted, respectively( P , .001), with diffusing capacity for nitric oxide and carbon monoxide ratios of 4.7 0.1 at sea level decreased to 3.6 0.1, 3.7 0.1, and 3.9 0.1, respectively ( P , .05) and a maximal exercise mean pulmonary arterial pressure at 56 4, 42 3, and 31 2 mm Hg, respectively ( P , .001). CONCLUSIONS: The aerobic exercise capacity of patients with CMS is preserved in spite of severe pulmonary hypertension and relative hypoventilation, probably by a combination of increased oxygen carrying capacity of the blood and lung diffusion, the latter being predominantly due to an increased capillary blood volume. PMID- 22302298 TI - The role of conventional bronchoscopy in the workup of suspicious CT scan screen detected pulmonary nodules. AB - BACKGROUND: Up to 50% of the participants in CT scan lung cancer screening trials have at least one pulmonary nodule. To date, the role of conventional bronchoscopy in the workup of suspicious screen-detected pulmonary nodules is unknown. If a bronchoscopic evaluation could be eliminated, the cost effectiveness of a screening program could be enhanced and the potential harms of bronchoscopy avoided. METHODS: All consecutive participants with a positive result on a CT scan lung cancer screening between April 2004 and December 2008 were enrolled. The diagnostic sensitivity and negative predictive value were calculated at the level of the suspicious nodules. In 95% of the nodules, the gold standard for the outcome of the bronchoscopy was based on surgical resection specimens. RESULTS: A total of 318 suspicious lesions were evaluated by bronchoscopy in 308 participants. The mean +/- SD diameter of the nodules was 14.6 +/- 8.7 mm, whereas only 2.8% of nodules were > 30 mm in diameter. The sensitivity of bronchoscopy was 13.5% (95% CI, 9.0%-19.6%); the specificity, 100%; the positive predictive value, 100%; and the negative predictive value, 47.6% (95% CI, 41.8%-53.5%). Of all cancers detected, 1% were detected by bronchoscopy only and were retrospectively invisible on both low-dose CT scan and CT scan with IV contrast. CONCLUSION: Conventional white-light bronchoscopy should not be routinely recommended for patients with positive test results in a lung cancer screening program. PMID- 22302299 TI - Transvenous phrenic nerve stimulation in patients with Cheyne-Stokes respiration and congestive heart failure: a safety and proof-of-concept study. AB - BACKGROUND: Cheyne-Stokes respiration (CSR), which often occurs in patients with congestive heart failure (CHF), may be a predictor for poor outcome. Phrenic nerve stimulation (PNS) may interrupt CSR in patients with CHF. We report the clinical use of transvenous PNS in patients with CHF and CSR. METHODS: Nineteen patients with CHF and CSR were enrolled. A single stimulation lead was placed at the junction between the superior vena cava and brachiocephalic vein or in the left-side pericardiophrenic vein. PNS stimulation was performed using Eupnea System device (RespiCardia Inc). Respiratory properties were assessed before and during PNS. PNS was assessed at a maximum of 10 mA. RESULTS: Successful stimulation capture was achieved in 16 patients. Failure to capture occurred in three patients because of dislocation of leads. No adverse events were seen under maximum normal stimulation parameters for an overnight study. When PNS was applied following a series of central sleep apneic events, a trend toward stabilization of breathing and heart rate as well as improvement in oxygen saturation was seen. Compared with pre-PNS, during PNS there was a significant decrease in apnea-hypopnea index (33.8 +/- 9.3 vs 8.1 +/- 2.3, P = .00), an increase in mean and minimal oxygen saturation as measured by pulse oximetry (89.7% +/- 1.6% vs 94.3% +/- 0.9% and 80.3% +/- 3.7% vs 88.5% +/- 3.3%, respectively, all P = .00) and end-tidal CO2 (38.0 +/- 4.3 mm Hg vs 40.3 +/- 3.1 mm Hg, P = .02), but no significant difference in sleep efficiency (74.6% +/- 4.1% vs 73.7% +/- 5.4%, P = .36). CONCLUSIONS: The preliminary results showed that in a small group of patients with CHF and CSR, 1 night of unilateral transvenous PNS improved indices of CSR and was not associated with adverse events. PMID- 22302300 TI - Prognostic impact of cancer-associated stromal cells in patients with stage I lung adenocarcinoma. AB - BACKGROUND: The tumor microenvironment, of which cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) are the major cellular components, plays an important role in tumor progression. This study evaluated the significance of podoplanin-positive CAFs and CD204-positive TAMs, which may reflect tumor-promoting CAFs and TAMs, as risk factors for recurrence in patients with stage I lung adenocarcinoma. METHODS: The expression of podoplanin in CAFs and CD204 in TAMs was analyzed by immunohistochemistry in 304 patients with stage I lung adenocarcinoma who underwent surgical resection between September 1992 and July 2004. The recurrence-free proportion (RFP) was estimated using the Kaplan Meier method. RESULTS: The presence of podoplanin-positive CAFs and the higher number of CD204-positive TAMs were associated with a lower 5-year RFP (P < .001 and P = .001, respectively). Podoplanin-positive CAFs were an independently statistically significant risk factor for recurrence with the highest hazard ratio (3.474, P = .029, by multivariate Cox proportional hazards model). According to subgroup analyses combining podoplanin-positive CAFs and other independent risk factors (visceral pleural invasion and intratumoral vascular invasion), the 5-year RFPs were 95.6%, 92.3%, 80.5%, and 30.3% (P = .294, P = .067, and P < .001) for patients with zero, one, two, or three risk factors, respectively. CONCLUSIONS: Podoplanin-positive CAFs were the most powerful independent risk factor for recurrence in patients with stage I lung adenocarcinoma. Podoplanin-positive CAFs may be useful for identifying patients with a high risk of recurrence who might benefit from adjuvant chemotherapy. PMID- 22302301 TI - Trends in bronchiectasis among medicare beneficiaries in the United States, 2000 to 2007. AB - BACKGROUND: Bronchiectasis is a potentially serious condition characterized by permanent and abnormal widening of the airways, the prevalence of which is not well described. We sought to describe the trends, associated conditions, and risk factors for bronchiectasis among adults aged >= 65 years. METHODS: A 5% sample of the Medicare outpatient claims database was analyzed for bronchiectasis trends among beneficiaries aged >= 65 years from 2000 to 2007. Bronchiectasis was identified using International Classification of Diseases, Ninth Revision, Clinical Modification claim diagnosis codes for acquired bronchiectasis. Period prevalence was used to describe sex- and race/ethnicity-specific rates, and annual prevalence was used to describe trends and age-specific rates. We estimated trends using Poisson regression and odds of bronchiectasis using multivariate logistic regression. RESULTS: From 2000 to 2007, 22,296 people had at least one claim for bronchiectasis. The 8-year period prevalence of bronchiectasis was 1,106 cases per 100,000 people. Bronchiectasis increased by 8.7% per year. We identified an interaction between the number of thoracic CT scans and race/ethnicity; period prevalence varied by a greater degree by number of thoracic CT scans among Asians compared with whites or blacks. Among people with one CT scan, Asians had a 2.5- and 3.9-fold higher period prevalence compared with whites and blacks. CONCLUSIONS: Bronchiectasis prevalence increased significantly from 2000 to 2007 in the Medicare outpatient setting and varied by age, sex, and race/ethnicity. This increase could be due to a true increase in the condition or an increased recognition of previously undiagnosed cases. PMID- 22302302 TI - Esophageal pressures, polysomnography, and neurobehavioral outcomes of adenotonsillectomy in children. AB - BACKGROUND: Esophageal pressure monitoring during polysomnography in children offers a gold-standard, "preferred" assessment for work of breathing, but is not commonly used in part because prospective data on incremental clinical utility are scarce. We compared a standard pediatric apnea/hypopnea index to quantitative esophageal pressures as predictors of apnea-related neurobehavioral morbidity and treatment response. METHODS: Eighty-one children aged 7.8 +/- 2.8 (SD) years, including 44 boys, had traditional laboratory-based pediatric polysomnography, esophageal pressure monitoring, multiple sleep latency tests, psychiatric evaluations, parental behavior rating scales, and cognitive testing, all just before clinically indicated adenotonsillectomy, and again 7.2 +/- 0.8 months later. Esophageal pressures were used, along with nasal pressure monitoring and oronasal thermocouples, not only to identify respiratory events but also more quantitatively to determine the most negative esophageal pressure recorded and the percentage of sleep time spent with pressures lower than -10 cm H(2)O. RESULTS: Both sleep-disordered breathing and neurobehavioral measures improved after surgery. At baseline, one or both quantitative esophageal pressure measures predicted a disruptive behavior disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined attention-deficit/hyperactivity disorder, conduct disorder, or oppositional defiant disorder) and more sleepiness and their future improvement after adenotonsillectomy (each P < .05). The pediatric apnea/hypopnea index did not predict these morbidities or treatment outcomes (each P > .10). The addition of respiratory effort-related arousals to the apnea/hypopnea index did not improve its predictive value. Neither the preoperative apnea/hypopnea index nor esophageal pressures predicted baseline hyperactive behavior, cognitive performance, or their improvement after surgery. CONCLUSIONS: Quantitative esophageal pressure monitoring may add predictive value for some, if not all, neurobehavioral outcomes of sleep-disordered breathing. PMID- 22302303 TI - Evaluation of TAPSE as a measure of right ventricular output. AB - PURPOSE: This study was designed to show the relationship between tricuspid annular plane systolic excursion (TAPSE) and stroke volume (SV) by thermodilution using three different methods and also to assess whether TAPSE can track hemodynamic changes associated with volume loading and ephedrine administration. METHODS: This was an observational study in 61 elective patients with a pulmonary artery catheter who were undergoing coronary artery bypass graft surgery in a cardiac surgical centre. We measured TAPSE by three methods using transesophageal echocardiography: M mode, speckle tracking at the lateral wall, and tissue tracking at the inferior wall. There were two interventions: leg raising (volume recruitment) or administration of ephedrine 5 mg iv. Echo and hemodynamic measurements were performed before and after each intervention. RESULTS: Eleven patients were excluded due to poor imaging. There were 26 patients in the leg raising group and 24 patients in the ephedrine group. The correlation coefficient between stroke volume (SV) and TAPSE by M mode, speckle tracking, and tissue tracking was 0.48, 0.44, and 0.09, respectively. There was a significant increase in SV following each intervention; however, the changes in TAPSE by any method and velocity were not large enough to reach statistical significance. CONCLUSION: Tricuspid annular plane systolic excursion by M mode and by speckle tracking correlates modestly with SV. There was no correlation between TAPSE and SV by tissue tracking at the inferior wall of the right ventricle. Tricuspid annular plane systolic excursion by M mode and by speckle tracking does not track changes in SV following either volume loading or ephedrine administration. PMID- 22302304 TI - A customized stylet for GlideScope(r) insertion of double lumen tubes. PMID- 22302305 TI - Best evidence in critical care medicine. Early versus late parenteral nutrition in the adult ICU: feeding the patient or our conscience? PMID- 22302306 TI - Phosphorylation of GIT1 tyrosine 321 is required for association with FAK at focal adhesions and for PDGF-activated migration of osteoblasts. AB - Osteoblast migration and proliferation are fundamental processes in bone healing. We demonstrated that the G-protein-coupled receptor kinase interacting protein 1(GIT1) is a key regulator of bone mass and osteoblast cell migration, but little is known about GIT1 regulation by upstream signaling systems or the impact of GIT1 on downstream effectors. We found that platelet-derived growth factor (PDGF) stimulated the GIT1 tyrosine phosphorylation in osteoblast cells and increased the association of GIT1 with focal adhesion kinase (FAK) at osteoblast focal adhesions. The Src inhibitor PP2 and FAK siRNA inhibited GIT1 tyrosine phosphorylation and the increased association between GIT1 and FAK following stimulation with PDGF. The spa2 homology domain (SHD) of GIT1 was required for association with FAK. Furthermore, phosphorylation of tyrosine 321 of GIT1, which is localized within the SHD, was critical for association with FAK. Mutagenesis analysis revealed that GIT1Y321F inhibited the increased association between GIT1 and FAK. Immunofluorescent staining revealed that GIT1Y321F inhibited FAK activation in focal adhesions after PGDF stimulation. A cell spreading assay demonstrated that GIT1Y321F also inhibited osteoblast cell motility, while the Boyden chamber assay demonstrated that the GIT1Y321F mutation inhibited PDGF induced osteoblastic cell migration. Phosphorylation of tyrosine 321 of GIT1 is necessary for PDGF-induced association with FAK, FAK activation in focal adhesions, and for osteoblastic cell migration. PMID- 22302307 TI - Impact of maternal characteristics on fetal growth in the third trimester: a population-based study. AB - OBJECTIVES: To investigate the association between maternal characteristics and fetal growth during the third trimester of pregnancy. METHODS: Using a population based perinatal register, 48809 term singleton pregnancies were identified for which a routine ultrasound examination in the third trimester had been performed between 1995 and 2009. Fetal and infant weight were expressed as gestational age specific standard deviation scores (z-scores) using a Swedish ultrasound-based reference curve. The growth of each fetus was assessed using the difference between the birth-weight z-score and the fetal-weight z-score estimated at the ultrasound examination, adjusted for gestational age, and divided by the time elapsed between the ultrasound examination and delivery. Analyses were performed using multivariable linear and polynomial regression analyses. RESULTS: Positive associations were found between maternal body mass index (BMI), height, pre existing diabetes mellitus, female fetal gender and fetal growth, whereas maternal smoking had a negative association. In the univariate analyses, primiparity and parity with four or more previous children were significantly associated with reduced fetal growth, but in the multivariable analysis, no association between parity and fetal growth could be detected. Both univariate and multivariable analyses revealed a significant inverse U-shaped association between maternal age and fetal growth. CONCLUSIONS: Third-trimester fetal growth was positively associated with increasing maternal BMI, height and pre-existing diabetes mellitus, and negatively associated with maternal smoking. PMID- 22302309 TI - Concise synthesis of an enantiopure bicyclic pyrazinone as constrained peptidomimetic building block. AB - A concise synthetic route has been developed for the preparation of a constrained peptidomimetic pyrazinone building block. From hydroxy-L-lysine, the desired pyrazinone is obtained in 43% overall yield (6 steps) via an efficient deprotection-double cyclization sequence. PMID- 22302308 TI - Reorganization of Cajal bodies and nucleolar targeting of coilin in motor neurons of type I spinal muscular atrophy. AB - Type I spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by loss or mutations of the survival motor neuron 1 (SMN1) gene. The reduction in SMN protein levels in SMA leads to degeneration and death of motor neurons. In this study, we have analyzed the nuclear reorganization of Cajal bodies, PML bodies and nucleoli in type I SMA motor neurons with homozygous deletion of exons 7 and 8 of the SMN1 gene. Western blot analysis is is revealed a marked reduction of SMN levels compared to the control sample. Using a neuronal dissociation procedure to perform a careful immunocytochemical and quantitative analysis of nuclear bodies, we demonstrated a severe decrease in the mean number of Cajal bodies per neuron and in the proportion of motor neurons containing these structures in type I SMA. Moreover, most Cajal bodies fail to recruit SMN and spliceosomal snRNPs, but contain the proteasome activator PA28, a molecular marker associated with the cellular stress response. Neuronal stress in SMA motor neurons also increases PML body number. The existence of chromatolysis and eccentric nuclei in SMA motor neurons correlates with Cajal body disruption and nucleolar relocalization of coil in, a Cajal body marker. Our results indicate that the Cajal body is a pathophysiological target in type I SMA motor neurons. They also suggest the Cajal body-dependent dysfunction of snRNP biogenesis and, therefore, pre-mRNA splicing in these neurons seems to be an essential component for SMA pathogenesis. PMID- 22302310 TI - In ovo effects of perfluorohexane sulfonate and perfluorohexanoate on pipping success, development, mRNA expression, and thyroid hormone levels in chicken embryos. AB - Perfluoroalkyl acids (PFAAs), specifically perfluorinated sulfonates and carboxylates, are synthetic substances known for their chemical stability, resistance to degradation, and potential to biomagnify in food chains. The toxicological and biological effects of PFAAs in avian species are not well characterized, although there is some evidence to suggest that they can impact neurodevelopment and hatching success. Our laboratory recently reported significant effects of perfluorohexane sulfonate (PFHxS) and perfluorohexanoate (PFHxA) on messenger RNA (mRNA) levels of thyroid hormone (TH)-responsive genes in chicken embryonic neuronal cells. In this study, we determined in ovo effects of PFHxS and PFHxA exposure (maximum dose = 38,000 and 9700 ng/g egg, respectively) on embryonic death, developmental endpoints, tissue accumulation, mRNA expression in liver and cerebral cortex, and plasma TH levels. Pipping success was reduced to 63% at the highest dose of PFHxS; no effects were observed for PFHxA. PFHxS exposure (38,000 ng/g) decreased tarsus length and embryo mass. PFHxS and PFHxA accumulated in the three tissue compartments analyzed as follows: yolk sac > liver > cerebral cortex. Type II and type III 5'-deiodinases (D2 and D3) and cytochrome P450 3A37 mRNA levels were induced in liver tissue of chicken embryos exposed to PFHxS, whereas D2, neurogranin (RC3), and octamer motif binding factor 1 mRNA levels were upregulated in cerebral cortex. Plasma TH levels were reduced in a concentration-dependent manner following PFHxS exposure; PFHxA had no effect. This in ovo study successfully validated previous in vitro results concerning the modulation of TH-responsive genes and identified adverse effects associated with TH homeostasis in response to PFHxS treatment. PMID- 22302311 TI - Differential gene expression responses distinguish contact and respiratory sensitizers and nonsensitizing irritants in the local lymph node assay. AB - Genomic approaches have the potential to enhance the specificity and predictive accuracy of existing toxicology endpoints, including those for chemical sensitization. The present study was conducted to determine whether gene expression responses can distinguish contact sensitizers (1-chloro-2,4 dinitrobenzene [DNCB] and hexyl cinnamic aldehyde [HCA]), respiratory sensitizers (ortho-phthalaldehyde and trimellitic anhydride [TMA]), and nonsensitizing irritants (methyl salicylate [MS] and nonanoic acid [NA]) in the local lymph node assay (LLNA). Female Balb/c mice received doses of each chemical as per the standard LLNA dosing regimen on days 1, 2, and 3. Auricular lymph nodes were analyzed for tritiated thymidine ((3)HTdR) incorporation on day 6 and for gene expression responses on days 6 and 10. All chemicals induced dose-dependent increases in stimulation index, which correlated strongly with the number of differentially expressed genes. A majority of genes modulated by the irritants were similarly altered by the sensitizers, consistent with the irritating effects of the sensitizers. However, a select number of responses involved with immune specific functions, such as dendritic cell activation, were unique to the sensitizers and may offer the ability to distinguish sensitizers from irritants. Genes for the mast cell proteases 1 and 8, Lgals7, Tim2, Aicda, Il4, and Akr1c18 were more strongly regulated by respiratory sensitizers compared with contact sensitizers and may represent potential biomarkers for discriminating between contact and respiratory sensitizers. Collectively, these data suggest that gene expression responses may serve as useful biomarkers to distinguish between respiratory and contact sensitizers and nonsensitizing irritants in the LLNA. PMID- 22302312 TI - Overexpression of rice CBS domain containing protein improves salinity, oxidative, and heavy metal tolerance in transgenic tobacco. AB - We have recently identified and classified a cystathionine beta-synthase domain containing protein family in Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa L.). Based on the microarray and MPSS data, we have suggested their involvement in stress tolerance. In this study, we have characterized a rice protein of unknown function, OsCBSX4. This gene was found to be upregulated under high salinity, heavy metal, and oxidative stresses at seedling stage. Transgenic tobacco plants overexpressing OsCBSX4 exhibited improved tolerance toward salinity, heavy metal, and oxidative stress. This enhanced stress tolerance in transgenic plants could directly be correlated with higher accumulation of OsCBSX4 protein. Transgenic plants could grow and set seeds under continuous presence of 150 mM NaCl. The total seed yield in WT plants was reduced by 80%, while in transgenic plants, it was reduced only by 15-17%. The transgenic plants accumulated less Na+, especially in seeds and maintained higher net photosynthesis rate and Fv/Fm than WT plants under NaCl stress. Transgenic seedlings also accumulated significantly less H2O2 as compared to WT under salinity, heavy metal, and oxidative stress. OsCBSX4 overexpressing transgenic plants exhibit higher abiotic stress tolerance than WT plants suggesting its role in abiotic stress tolerance in plants. PMID- 22302313 TI - Molecular Studies on the Transmission of Indian Cassava Mosaic Virus (ICMV) and Sri Lankan Cassava Mosaic Virus (SLCMV) in Cassava by Bemisia tabaci and Cloning of ICMV and SLCMV Replicase Gene from Cassava. AB - Cassava mosaic disease, caused by cassava mosaic geminiviruses are transmitted by Bemisia tabaci. The B. tabaci adults from colonies reared on virus free cassava plant produced from apical meristem culture was studied to determine their ability to transmit Indian cassava mosaic virus (ICMV) and Sri Lankan cassava mosaic virus (SLCMV) from cassava to cassava. Virus free plants were confirmed by polymerase chain reaction (PCR) using geminivirus degenerate primers. The virus acquisition access period (AAP) of 48 h on virus infected cassava leaves and 48 h virus inoculation access periods on virus free healthy leaves were investigated. Both ICMV and SLCMV were absolutely transmitted by whiteflies reared on cassava. Virus specific primers were designed in the replicase region and used to detect virus in B. tabaci after different AAP. The PCR amplified replicase genes from virus transmitted cassava leaves were cloned the plasmid DNA was isolated from a recombinant colony of E. coli DH5alpha after their confirmation by colony PCR and sequenced them. The nucleotide sequences obtained from automated DNA sequencing were confirmed as ICMV and SLCMV replicase gene after homology searching by BLAST and found to be a new isolates. The nucleotide sequences of new isolates were submitted in GenBank (accession number JN652126 and JN595785). PMID- 22302314 TI - Human-induced pluripotent stem cells: in quest of clinical applications. AB - In the field of regenerative medicine, the development of induced pluripotent stem (iPS) cells may represent a potential strategy to overcome the limitations of human embryonic stem cells (ESCs). iPS cells have the potential to mimic human disease, since they carry the genome of the donor. Hypothetically, with iPS cell technology it is possible to screen patients for a genetic cause of disease (genetic mutation), develop cell lines, reprogram them back to iPS cells, finally differentiate them into one or more cell types that develop the disease. Although the creation of multiple lineages with iPS cells can seem limitless, a number of challenges need to be addressed in order to effectively use these cell lines for disease modeling. These include the low efficiency of iPS cell generation without genetic alterations, the possibility of tumor formation in vivo, the random integration of retroviral-based delivery vectors into the genome, and unregulated growth of the remaining cells that are partially reprogrammed and refractory to differentiation. The establishment of protein or RNA-based reprogramming strategies will help generate human iPS cells without permanent genetic alterations. Finally, direct reprogramming strategies can provide rapid production of models of human "diseases in a dish", without first passing the cells through a pluripotent state, so avoiding the challenges of time-consumming and labor-intensive iPS cell line generation. This review will overview methods to develop iPS cells, current strategies for direct reprogramming, and main applications of iPS cells as human disease model, focusing on human cardiovascular diseases, with the aim to be a potential information resource for biomedical scientists and clinicians who exploit or intend to exploit iPS cell technology in a range of applications. PMID- 22302315 TI - Campylobacter fetus infection in three rheumatoid arthritis patients treated with rituximab. PMID- 22302316 TI - Short- and long-term efficacy of intra-articular injections with betamethasone as part of a treat-to-target strategy in early rheumatoid arthritis: impact of joint area, repeated injections, MRI findings, anti-CCP, IgM-RF and CRP. AB - OBJECTIVE: To investigate the short-term and long-term efficacy of intra articular betamethasone injections, and the impact of joint area, repeated injections, MRI pathology, anticyclic citrullinated peptide (CCP) and immunoglobulin M rheumatoid factor (IgM-RF) status in patients with early rheumatoid arthritis (RA). METHODS: During 2 years of follow-up in the CIMESTRA trial, 160 patients received intra-articular betamethasone in up to four swollen joints/visit in combination with disease-modifying antirheumatic drugs. Short term efficacy was assessed by EULAR good response. Long-term efficacy by Kaplan Meier plots of the joint injection survival (ie, the time between injection and renewed flare). Potential predictors of joint injection survival were tested. RESULTS: 1373 Unique joints (ankles, elbows, knees, metacarpophalangeal (MCP), metatarsophalangeal, proximal interphalangeal (PIP), shoulders, wrists) were injected during 2 years. 531 Joints received a second injection, and 262 a third. At baseline, the median numbers of injections (dose of betamethasone) was 4 (28 mg), declining to 0 (0 mg) at subsequent visits. At weeks 2, 4 and 6, 50.0%, 58.1% and 61.7% had achieved a EULAR good response. After 1 and 2 years, respectively, 62.3% (95% CI 58.1% to 66.9%) and 55.5% (51.1% to 60.3%) of the joints injected at baseline had not relapsed. All joint areas had good 2-year joint injection survival, longest for the PIP joints: 73.7% (79.4% to 95.3%). 2 Year joint injection survival was higher for first injections: 56.6% (53.7% to 59.8%) than for the second: 43.4% (38.4% to 49.0%) and the third: 31.3% (25.0% to 39.3%). Adverse events were mild and transient. A high MRI synovitis score of MCP joints and anti-CCP-negativity were associated with poorer joint injection survival, whereas IgM-RF and C-reactive protein were not. CONCLUSION: In early RA, intra-articular injections of betamethasone in small and large peripheral joints resulted in rapid, effective and longlasting inflammatory control. The cumulative dose of betamethasone was low, and the injections were well tolerated. PMID- 22302317 TI - Rapidly involuting congenital haemangioma (RICH) of the liver. AB - BACKGROUND: Rapidly involuting congenital haemangioma (RICH) is a benign neoplasm that may occur in many locations in the body. When RICH occurs in the liver, it may be confused with other lesions. OBJECTIVE: To present a case series from a single institution. MATERIALS AND METHODS: Retrospective review of pathological and imaging findings in infants with biopsy-proven hepatic RICH treated at a single hospital. RESULTS: Four children (2 days to 6 weeks of age) presented between 2002 and 2007 with a solitary hepatic lesion. Needle biopsy excluded the alternative possibility of infantile haemangioma by showing negativity for GLUT1. Serial imaging confirmed rapid involution in each child. CONCLUSION: RICH should be suspected in neonates who present with a solitary liver lesion and normal-for age serum alpha-fetoprotein. Serial US scans should be used to confirm a progressive shrinkage of the lesion. Corticosteroids and beta2-adrenergic antagonists have no proven effect in treating RICH. If the lesion grows, percutaneous needle biopsy is recommended to exclude a malignant tumour and to direct further management. Infants with cardiac failure should be treated medically. Embolization (with or without needle biopsy) should only be performed when this strategy fails. PMID- 22302318 TI - CT radiation dose reduction: can we do harm by doing good? PMID- 22302319 TI - Reply to commentary--'CT radiation dose reduction: can we do harm by doing good?'. PMID- 22302320 TI - Integrated microfluidics platforms for investigating injury and regeneration of CNS axons. AB - We describe the development of experimental platforms to quantify the regeneration of injured central nervous system (CNS) neurons by combining engineering technologies and primary neuronal cultures. Although the regeneration of CNS neurons is an important area of research, there are no currently available methods to screen for drugs. Conventional tissue culture based on Petri dish does not provide controlled microenvironment for the neurons and only provide qualitative information. In this review, we introduced the recent advances to generate in vitro model system that is capable of mimicking the niche of CNS injury and regeneration and also of testing candidate drugs. We reconstructed the microenvironment of the regeneration of CNS neurons after injury to provide as in vivo like model system where the soluble and surface bounded inhibitors for regeneration are presented in physiologically relevant manner using microfluidics and surface patterning methods. The ability to control factors and also to monitor them using live cell imaging allowed us to develop quantitative assays that can be used to compare various drug candidates and also to understand the basic mechanism behind nerve regeneration after injury. PMID- 22302321 TI - Deterioration of stress distribution due to tunnel creation in single-bundle and double-bundle anterior cruciate ligament reconstructions. AB - Bone tunnel enlargement is a common effect associated with knee laxity after anterior cruciate ligament(ACL) reconstruction. Nevertheless, its exact pathomechanism remains controversial. One of the possible reasons could be bone remodeling due to tunnel creation, which changes the stress environment in the joint. The present study aims to characterize the deteriorated stress distribution on the articular surface, which is due to tunnel creation after single-bundle or double-bundle ACL reconstruction. The stress distributions in the knee following ACL reconstruction under the compression, rotation, and valgus torques were calculated using a validated three-dimensional finite element(FE) model. The results indicate that, (a) under compression,von Mises stress is decreased at lateral and posteromedial regions of single/anteromedial (AM) tunnel, whereas it is increased at anterior region of single/AM tunnel in tibial subchondral bone; (b) the concentration of tensile stress is transferred from the articular surface to the location of graft fixation, and tensile stress in subchondral plate is decreased after ACL reconstruction; (c) severe stress concentration occurs between AM and posterolateral tunnels following the double bundle reconstruction, which may contribute to the tunnel communication after surgery. In summary, the present study affirms that the deterioration of stress distribution occurs near the articular surface, which may cause the collapse of the tunnel wall, and lead to tunnel enlargement.The present study provides an insight into the effect of tunnel creation on articular stress deterioration after single-bundle or double-bundle ACL reconstruction. These findings provide knowledge on the effect of tunnel enlargement after ACL reconstruction in the long term. PMID- 22302322 TI - Leadership. PMID- 22302324 TI - Economic grand rounds: the price is right? Changes in the quantity of services used and prices paid in response to parity. AB - The impact of parity coverage on the quantity of behavioral health services used by enrollees and on the prices of these services was examined in a set of Federal Employees Health Benefit (FEHB) Program plans. After parity implementation, the quantity of services used in the FEHB plans declined in five service categories, compared with plans that did not have parity coverage. The decline was significant for all service types except inpatient care. Because a previous study of the FEHB Program found that total spending on behavioral health services did not increase after parity implementation, it can be inferred that average prices must have increased over the period. The finding of a decline in service use and increase in prices provides an empirical window on what might be expected after implementation of the federal parity law and the parity requirement under the health care reform law. PMID- 22302325 TI - Mental health reforms in Europe: Israel's rehabilitation in the community of persons with mental disabilities law: challenges and opportunities. AB - This column describes an innovative, government-sponsored, countrywide mental health reform focusing on rehabilitation and community integration of persons with serious mental illness, which was enacted into law in Israel in 2000. The reform was part of the country's efforts to shift the locus of treatment and care from psychiatric institutions to the community. The authors review preliminary evidence of the impact of reform and offer cautionary notes regarding the future direction of its implementation. The decade after the law's enactment saw an impressive increase in rehabilitation services, a significant reduction in the number of psychiatric beds, and major changes in government budget allocations. The authors examine factors that may endanger the viability of reform and discuss lessons to be learned from the Israeli experience. PMID- 22302326 TI - Personal accounts: surviving and thriving after years of misdiagnosis. PMID- 22302327 TI - Medication use and spending trends among children with ADHD in Florida's Medicaid program, 1996-2005. AB - OBJECTIVE: How the introduction of new pharmaceuticals affects spending for treatment of children with attention-deficit hyperactivity disorder (ADHD) is unknown. This study examined trends in use of pharmaceuticals and their costs among children with ADHD from 1996 to 2005. METHODS: This observational study used annual cohorts of children ages three to 17 with ADHD (N=107,486 unique individuals during the study period) from Florida Medicaid claims to examine ten year trends in the predicted probability for medication use for children with ADHD with and without psychiatric comorbidities as well as mental health spending and its components. Additional outcome measures included average price per day and average number of days filled for medication classes. RESULTS: Overall, the percentage of children with ADHD treated with ADHD drugs increased from 60% to 63%, and the percentage taking antipsychotics more than doubled, from 8% to 18%. In contrast, rates of antidepressant use declined from 21% to 15%, and alpha agonist use was constant, at 15%. Mental health spending increased 61%, with pharmaceutical spending representing the fastest-rising component (up 192%). Stimulant spending increased 157%, mostly because of increases in price per prescription. Antipsychotic spending increased 588% because of increases in both price and quantity (number of days used). By 2005, long-acting ADHD drugs accounted for over 90% of stimulant spending. CONCLUSIONS: Long-acting ADHD drugs have rapidly replaced short-acting stimulant use among children with ADHD. The use of antipsychotics as a second-tier agent in treating ADHD has overtaken traditional agents such as antidepressants or alpha agonists, suggesting a need for research into the efficacy and side effects of second-generation antipsychotics among children with ADHD. PMID- 22302328 TI - Treatment of attention-deficit hyperactivity disorder: patterns of evolving care during the first treatment episode. AB - OBJECTIVE: This study sought to better understand factors associated with different patterns of treatment among children starting treatment for attention deficit hyperactivity disorder (ADHD). METHODS: Factors associated with service utilization and pharmacy claims data for 2,077 Medicaid-enrolled children aged six to 12 who started treatment for ADHD between October 2006 and December 2007 in a large mid-Atlantic state were investigated by using logistic regressions and Cox proportional hazard models. RESULTS: A total of 45% of children started ADHD treatment with a psychosocial intervention alone, 41% of children started treatment with medication alone, and 14% of children started treatment with a combination of both treatments. By the end of the treatment episode, 42% of children who initiated treatment with psychosocial interventions alone had added medication. Within six months of starting treatment, approximately 40% of children had discontinued treatment. Among those who continued receiving treatment, a majority received medication, either alone or with a psychosocial intervention. Treatment with a psychosocial intervention was significantly more likely to be initiated among nonwhite versus white children and among younger versus older children. Younger versus older children and African-American versus Caucasian children were significantly more likely to drop out of treatment sooner. CONCLUSIONS: During the first episode of treatment for ADHD, the interventions children received frequently changed, suggesting dissatisfaction with initial treatment. Further research is needed to better understand what underlies the patterns of evolving care so that all families seeking care for children with ADHD may receive preferred and effective treatment. PMID- 22302329 TI - A national survey of U.S. juvenile mental health courts. AB - OBJECTIVE: The authors surveyed U.S. juvenile mental health courts (JMHCs). METHODS: Forty-one were identified in 15 states, and 34 returned surveys; one was completed on the basis of published information. Topics included the court's history, youths served, inclusion and exclusion criteria, the court process, and services provided. RESULTS: Half (51%) reported that the juvenile court was responsible for the program; for 11% the probation agency had the responsibility, and 17% reported shared responsibility by these entities. Fifty-one percent reported that all youths with any mental disorder diagnosis are eligible. The most commonly reported participant diagnoses are bipolar disorder (27%), depression (23%), and attention-deficit hyperactivity disorder (16%). Seventy percent currently include participants with felony offenses, and 91% with misdemeanors; 67% exclude status offenses, and 21% exclude violent offenses. A guilty plea was required by 63%. Incentives to participate included dismissal of charges (40%), reduction in court hearings (43%), praise by the judge and probation officer (60%), reduction in curfew restrictions (23%), and gift cards or gifts (71%). Sanctions for not participating included increased supervision or hearings (60%), performing community service (54%), and placement in residential detention (60%). Most JMHCs reported use of a multidisciplinary team to coordinate community-based services to prevent protracted justice system involvement. CONCLUSIONS: JMHCs are being developed in the absence of systematically collected outcome data. Although they resemble adult mental health courts, they have unique features that are specific to addressing the complex needs of youths with mental disorders involved in the justice system. These include diagnostic and treatment challenges and issues related to involving families and schools. PMID- 22302330 TI - Impact of capacity reductions in acute public-sector inpatient psychiatric services. AB - OBJECTIVE: This study tested the hypothesis that reductions in acute public sector psychiatric inpatient capacity in a major urban area would be associated with negative impacts on patients and the community. METHODS: The impact of two discrete service changes that reduced acute inpatient capacity by 50% in a single public-sector general hospital setting was examined. Indicators of impact were obtained from existing administrative databases for a 33-month period. Indicators included measures of utilization and case mix on the acute inpatient and psychiatric emergency services, suicides among community mental health clients, and psychiatric evaluations conducted in county jails. RESULTS: Reductions in inpatient capacity were not associated with hypothesized negative impacts, such as increased demand for psychiatric emergency services, decreased access to emergency or inpatient services, or increased recidivism to inpatient care. Similarly, neither the number of suicides among community mental health clients nor the number of jail psychiatric evaluations increased after capacity reduction. CONCLUSIONS: Data from a single urban public-sector setting suggest that acute inpatient psychiatric capacity may be reduced without negative impacts on patients or the community. In this setting, collaboration between inpatient and outpatient providers to speed discharge facilitated reductions in inpatient length of stay that made it possible to serve the same number of patients with fewer resources. Other service system adjustments may be more appropriate in other settings, and alternative approaches to reducing utilization of high-cost inpatient care warrant examination. PMID- 22302331 TI - Unconventional mental health treatment: reexamining the racial-ethnic disparity in treatment-seeking behavior. AB - OBJECTIVE: The aim of this study was to examine whether a more inclusive definition of mental health treatment that incorporates unconventional treatment may partially account for the racial disparity in treatment-seeking behavior. METHODS: Using 2005-2007 pooled data (N=102,749) from the National Survey on Drug Use and Health (NSDUH), logistic regression models were used to examine the relationship between race (non-Hispanic white, non-Hispanic black, and Hispanic) and the type of mental health treatment sought. Treatment types were classified as conventional care (outpatient or inpatient), psychotropic medication, or unconventional treatment. Unconventional treatment was further classified as complementary and alternative medicine or parochial care, defined as treatment that appeals to a specific religious group that is provided at no cost outside a health delivery system. RESULTS: Compared with whites, blacks had 53% lower odds and Hispanics had 41% lower odds of seeking any type of mental health treatment in the past year. Both blacks and Hispanics were significantly less likely to report use of any single type of conventional or unconventional mental health treatment other than parochial care. Blacks had 60% greater odds and Hispanics had 36% greater odds than whites of using parochial care only. CONCLUSIONS: Although blacks and Hispanics were more likely than whites to use parochial mental health treatment, accounting for use of this type of unconventional treatment did not explain the racial disparity in treatment-seeking behavior. PMID- 22302332 TI - Using the cultural formulation to resolve uncertainty in diagnoses of psychosis among ethnoculturally diverse patients. AB - OBJECTIVE: The aim of the study was to assess the impact of systematic use of the DSM-IV-TR cultural formulation on diagnoses of psychotic disorders among patients of ethnic minority and immigrant backgrounds referred to a cultural consultation service (CCS) in Canada. METHODS: The study entailed a review of medical records and case conference transcripts of 323 patients seen in a ten-year period at the CCS to determine factors associated with change in the diagnosis of psychotic disorders by the CCS. Logistic regression analysis was used to identify variables associated with changes in diagnosis. RESULTS: A total of 34 (49%) of the 70 cases with an intake (referral) diagnosis of a psychotic disorder were rediagnosed as nonpsychotic disorders, whereas only 12 (5%) of the 253 cases with an intake diagnosis of a nonpsychotic disorder were rediagnosed as a psychotic disorder (p<.001). Major depression, posttraumatic stress disorder (PTSD), adjustment disorder, and bipolar affective disorder were the common disorders diagnosed with use of the cultural formulation. Rediagnosis of a psychotic disorder as a nonpsychotic disorder was significantly associated with being a recent arrival in Canada (odds ratio [OR]=6.05, 95% confidence interval [CI]=1.56 23.46, p=.009), being nonblack (OR=3.72, CI=1.03-13.41, p=.045), and being referred to the CCS by nonmedical routes (such as social work or occupational therapy) (OR=3.23, CI=1.03-10.13, p=.044). CONCLUSIONS: Misdiagnosis of psychotic disorders occurred with patients of all ethnocultural backgrounds. PTSD and adjustment disorder were misidentified as psychosis among immigrants and refugees from South Asia. Studies are needed that compare clinical outcomes of use of cultural consultation with outcomes from use of other cultural competence models. PMID- 22302333 TI - Concordance between psychotropic prescribing for veterans with PTSD and clinical practice guidelines. AB - OBJECTIVE: Clinical practice guidelines for the pharmacological treatment of posttraumatic stress disorder (PTSD) do not support the use of benzodiazepines and cite insufficient evidence to recommend mood stabilizers. Although guidelines previously recommended second-generation antipsychotics as adjunct medication, recent research findings have also brought this recommendation into question. This study aimed to determine which characteristics of veterans with diagnosed PTSD were associated with receiving prescriptions for benzodiazepines and mood stabilizers and second-generation antipsychotics. METHODS: The survey responses of 482 veterans with PTSD were combined with prescription information from Veterans Affairs national pharmacy databases. The researchers assessed the use of eight classes of psychotropics prescribed for patients with PTSD in the year after a new PTSD diagnosis. Multivariate logistic regressions identified demographic characteristics, symptom severity, co-occurring psychiatric diagnoses, health service use, and attitudinal characteristics associated with prescribing of benzodiazepines, second-generation antipsychotics, and mood stabilizers. RESULTS: In the absence of a clearly indicated co-occurring psychiatric diagnosis, long-term benzodiazepines were prescribed to 14%, second generation antipsychotics to 15%, and mood stabilizers to 18% of veterans with PTSD. Benzodiazepine prescribing was associated with symptoms of insomnia. Having a mental health inpatient stay (odds ratio [OR]=8.01, p<.001) and at least one psychotherapy visit (OR=5.37, p<.001) were predictors of being prescribed a second-generation antipsychotic. Reporting more symptom severity (OR=1.84, p<.001) and fewer alcohol use problems (OR=.36, p<.03) predicted being prescribed a mood stabilizer. CONCLUSIONS: Prescribing patterns appeared generally consistent with treatment guidelines. Notable exceptions and areas worthy of future attention are discussed. PMID- 22302334 TI - Text message reminders of appointments: a pilot intervention at four community mental health clinics in London. AB - OBJECTIVE: Forgetting is commonly stated as a reason for missing mental health appointments. The authors examined the effect of short message service (SMS), or text message, reminders on the attendance of appointments at four community mental health clinics in London. METHODS: Attendance of outpatient appointments roughly between March and June of 2008 (N=648), 2009 (N=1,081), and 2010 (N=1,088) was examined. Reminder messages were sent seven and five days before an appointment in 2009 and seven and three days before an appointment in 2010; patients in the 2008 sample received no reminder messages. Appointment attendance during the sample periods was compared by using multiple logistic regression analysis and adjusting for sociodemographic and clinical confounders. RESULTS: Missed appointments accounted for 36% of appointments in 2008, 26% of appointments in 2009, and 27% of appointments in 2010. The relative risk reduction in failed attendance was 28% between the 2008 and 2009 samples and 25% between the 2008 and 2010 samples. Attendance rates were significantly higher for the 2009 and 2010 samples than for the 2008 sample (p<.001) but did not differ between the two intervention periods. CONCLUSIONS: SMS-based technology can offer a time-, labor-, and cost-efficient strategy for encouraging engagement with psychiatric outpatient services. In England alone, a reduction of 25% to 28% in missed outpatient clinic appointments would translate to national cost savings of more than L150 million, or $245 million, per year, and likely have clinical benefits as well. PMID- 22302335 TI - From adherence to self-determination: evolution of a treatment paradigm for people with serious mental illnesses. AB - Treatment adherence and nonadherence is the current paradigm for understanding why people with serious mental illnesses have low rates of participation in many evidence-based practices. The authors propose the concept of self-determination as an evolution in this explanatory paradigm. A review of the research literature led them to the conclusion that notions of adherence are significantly limited, promoting a value-based perspective suggesting people who do not opt for prescribed treatments are somehow flawed or otherwise symptomatic. Consistent with a trend in public health and health psychology, ideas of decisions and behavior related to health and wellness are promoted. Self-determination frames these decisions as choices and is described herein via the evolution of ideas from resistance and compliance to collaboration and engagement. Developments in recovery and hope-based mental health systems have shepherded interest in self determination. Two ways to promote self-determination are proffered: aiding the rational actor through approaches such as shared decision making and addressing environmental forces that are barriers to choice. Although significant progress has been made toward self-determination, important hurdles remain. PMID- 22302336 TI - Assortative mating. AB - Psychosocial programs that introduce young people with psychosis to each other encourage bonding and, perhaps, marriage. By providing such programs, are we unwittingly promoting assortative mating, with ill effects for offspring? Or, on the other hand, are we ensuring better health for young people with psychosis and perhaps laying the groundwork for stronger marital unions than they would otherwise have formed? Instead of steering young people with psychosis into specialized services, should we be "mainstreaming" them, equipping them in situ with the skills necessary to navigate the larger social world? Should we even be considering the welfare of future generations, or is this beyond psychiatry's ken? PMID- 22302337 TI - Customized adherence enhancement for individuals with bipolar disorder receiving antipsychotic therapy. AB - OBJECTIVE: A three-month prospective trial of a psychosocial intervention- customized adherence enhancement (CAE)--was conducted with 43 medication nonadherent individuals with bipolar disorder. METHODS: CAE modules were administered as indicated by a screen that identifies reasons for nonadherence. The primary outcome was change in adherence to mood-stabilizing medications as measured by the Tablet Routines Questionnaire and pill counts. Secondary outcomes included change in symptoms, measured by the Hamilton Rating Scale for Depression (HAM-D), Young Mania Rating Scale (YMRS), and Brief Psychiatric Rating Scale (BPRS). RESULTS: Participants completed 76% of sessions. Dropout at three months was 13 (30%). Adherence improved from a baseline mean+/-SD of 34%+/-27% of tablets missed in the past month to only 10%+/-15% (p<.001). BPRS, HAM-D, andYMRS scores all indicated significant improvement at three-month follow-up (p<.05). CONCLUSIONS: Although conclusions must be tempered by the uncontrolled design, CAE appeared to be well accepted and was associated with improvements in adherence, symptoms, and functioning. PMID- 22302338 TI - Characteristics of telemental health service use by American Indian veterans. AB - OBJECTIVE: This study examined use by American Indian and Alaska Native veterans of services provided by specialty telemental health clinics focused on posttraumatic stress disorder. These clinics offer services via videoconferencing to address challenges faced by rural veterans in accessing care. METHODS: A retrospective chart and electronic medical record review was conducted for 85 male veterans who used services at two rural telemental health clinics from 2001 through 2006. Service use and other characteristics were documented before and after their initial telemental health intake. RESULTS: After intake, patients' use of any health services (both general medical and mental health services) significantly increased (p<.01), as did the proportion receiving psychotropic medication (p<.01). CONCLUSIONS: This first examination of service use by American Indian and Alaska Native veterans at specialty telemental health clinics will help inform research and clinical strategies for improving telemental health for this and other rural populations. PMID- 22302339 TI - Pharmacotherapy regimens among patients with posttraumatic stress disorder and mild traumatic brain injury. AB - OBJECTIVE: The purpose of this study was to determine if veterans with posttraumatic stress disorder (PTSD) and mild traumatic brain injury (TBI) are treated differently pharmacologically than patients with PTSD alone. METHODS: A retrospective evaluation of PTSD pharmacotherapy of Operation Enduring Freedom/Operation Iraqi Freedom veterans with PTSD (N=707) was conducted between April 1, 2007, and March 31, 2009. A total of 45 veterans had suffered a mild TBI. RESULTS: Compared with the patients with PTSD alone, the patients with PTSD and TBI were more likely to be prescribed an antidepressant (p<.001), a sedative hypnotic (p<.001), or an antipsychotic (p=.024). The patients with TBI were also significantly more likely to receive psychotropic polypharmacy (p=.001) and to receive higher doses of psychiatric medications (p=.03). CONCLUSIONS: The differences in drug therapy found in this study may indicate that patients with TBI and PTSD respond differently to treatment than patients with PTSD alone. PMID- 22302340 TI - Suicide thoughts and attempts and psychiatric treatment utilization: informing prevention strategies. AB - OBJECTIVES: The aim of this study was to investigate the characteristics of nonreceipt of specialty psychiatric treatment among those who experienced suicidal thoughts or who attempted suicide. METHODS: Data were from the 2008-2009 National Survey on Drug Use and Health and included responses from adults 18 years and older who answered mental health and suicide-related questions (N=75,690). RESULTS: Overall, 3.7% of the respondents experienced suicidal thoughts and .5% attempted suicide. Lack of psychiatric treatment was common among these individuals. Men, 18- to 25-year-olds, persons without insurance, and racial-ethnic groups other than white non-Hispanics were least likely to receive treatment. CONCLUSIONS: Prevention and treatment efforts have targeted seekers of specialty treatment at high risk of suicide, but fewer interventions have focused on individuals with suicidal thoughts or attempters who do not seek treatment. More targeted prevention strategies are needed to mitigate suicide in the United States. PMID- 22302346 TI - Slow growth in U.S. health care spending continues. PMID- 22302348 TI - Transcatheter arterial embolization for upper gastrointestinal nonvariceal hemorrhage: is empiric embolization warranted? AB - PURPOSE: To determine whether transcatheter arterial embolization performed in the setting of active gastric or duodenal nonvariceal hemorrhage is efficacious when the bleeding source cannot be identified angiographically. METHODS: Records of 115 adult patients who underwent visceral angiography for endoscopically documented gastric (50 patients) or duodenal (65 patients) nonvariceal hemorrhage were retrospectively reviewed. Patients were subdivided into three groups according to whether angiographic evidence of arterial hemorrhage was present and whether embolization was performed (group 1 = no abnormality, no embolization; group 2 = no abnormality, embolization performed [empiric embolization]; and group 3 = abnormality present, embolization performed). Thirty-day rates and duration of primary hemostasis and survival were compared. RESULTS: For patients with gastric sources of hemorrhage, the rate of primary hemostasis at 30 days after embolization was greater when embolization was performed in the setting of a documented angiographic abnormality than when empiric embolization was performed (67% vs. 42%). The rate of primary hemostasis at 30 days after angiography was greater for patients with duodenal bleeding who either underwent empiric embolization (60%) or embolization in the setting of angiographically documented arterial hemorrhage (58%) compared with patients who only underwent diagnostic angiogram (33%). Patients with duodenal hemorrhage who underwent embolization were less likely to require additional invasive procedures to control rebleeding (p = 0.006). CONCLUSION: Empiric arterial embolization may be advantageous in patients with a duodenal source of hemorrhage but not in patients with gastric hemorrhage. PMID- 22302349 TI - A phase II trial of Erlotinib in combination with gemcitabine and cisplatin in advanced pancreatic cancer. AB - BACKGROUND: Gemcitabine has been recognized as a standard chemotherapy in advanced pancreas cancer(APC). We conducted a phase II study of a triple combination regimen (GPT) consisting of gemcitabine (G), cisplatin(P) and erlotinib (T) in patients with APC. PATIENTS AND METHODS: Chemotherapy-naive patients with locally advanced or metastatic, histologically confirmed adenocarcinoma of the pancreas were treated with erlotinib 100 mg daily, 1,000 mg/m2 of gemcitabine and 25 mg/m2 of cisplatin administered on days 1 and 8, respectively, every 3 weeks.The primary end point was objective response. Secondary end points included progression-free survival, overall survival and toxicity. The study was designed according to the optimal two-stage design. RESULTS: Twenty-two patients were enrolled between June 2009 and August 2010. No complete response was achieved and partial response was observed in 5 patients (26%), Stable disease in 7 (37%), and progressive disease in 7 (37%). The median time to progression was 4.0 months (95% CI: 2.9-5.1 months), and the median overall survival 6.8 months (95% CI: 3.7-9.9 months). The response rate in stage I reached the target (>=3/22,p0010%) established for movement to stage II but this study was determined to close earlier than planned because of unexpected treatment-related deaths (3 patients). CONCLUSION: The triple regimen of GPT is effective for APC. Treatment related mortalities factored early closure of this GPT protocol. Considering effect and toxicity, this triple regimen seems to offer few benefits to the patients compared with gemcitabine based doublets. (ClinicalTrials.gov number, NCT00922896). PMID- 22302350 TI - Somatic mutations in the Notch, NF-KB, PIK3CA, and Hedgehog pathways in human breast cancers. AB - Exome sequencing of human breast cancers has revealed a substantial number of candidate cancer genes with recurring but infrequent somatic mutations. To determine more accurately their mutation prevalence, we performed a mutation analysis of 36 novel candidate cancer genes in 96 human breast cancers. Somatic mutations with potential impact on protein function were observed in the genes ADAM12, CENTB1, CENTG1, DIP2C, GLI1, GRIN2D, HDLBP, IKBKB, KPNA5, NFKB1, NOTCH1, and OTOF. These findings strengthen the evidence for involvement of the Notch, Hedgehog, NF-KB, and PIK3CA pathways in breast cancer development, and point to novel processes that likely are involved. PMID- 22302351 TI - Comparison between the first and second versions of the Copenhagen Psychosocial Questionnaire: psychosocial risk factors for a high need for recovery after work. AB - PURPOSE: The Copenhagen Psychosocial Questionnaire (COPSOQ I) was developed as a tool to assess a broad range of psychosocial work environment factors and was recently revised (COPSOQ II). The research question in this study was: Do COPSOQ II-scales predict a high need for recovery (NFR) after work better than COPSOQ I scales? METHODS: A cross-sectional questionnaire study was conducted in 990 subjects (84.5% response), employed in the public sector. Psychosocial factors were assessed by COPSOQ I and COPSOQ II. Multivariate logistic regression analysis was used to calculate the odds ratios for the presence of a high NFR, controlled for gender, age, physical workload and other relevant occupational and non-occupational factors. Analyses were performed for COPSOQ I and COPSOQ II separately. RESULTS: In both COPSOQ versions, 'quantitative demands' (p < 0.001) and 'job insecurity' (p < 0.005) were significantly associated with a high NFR. Additionally, in the COPSOQ I model, 'demands for hiding emotions' (p < 0.05) and 'degrees of freedom' (p < 0.05), and in the COPSOQ II model 'emotional demands' (p < 0.05) and 'commitment to the workplace' (p < 0.005) were significant as well. 'Degrees of freedom' was omitted by the developers in the revised COPSOQ II. Reintroducing it into the COPSOQ II model did not alter the existing associations, but pointed out 'degrees of freedom' to be an additional important dimension (p < 0.05). The COPSOQ II model with 'degrees of freedom' included also had the best data fit. CONCLUSIONS: The results suggested the COPSOQ II to be better predictive than COPSOQ I for a high NFR, but also indicated that 'degrees of freedom' should be included into the COPSOQ II when studying the NFR as outcome parameter. PMID- 22302352 TI - Differential role of estrogen receptor beta in early versus metastatic non-small cell lung cancer. AB - Although women have an increased susceptibility to lung cancer, they also have a favorable clinical outcome. This may in part be due to female specific genetic and hormonal factors. In the present study, expression of ER-beta was investigated by immunohistochemistry using tissue samples from two cohorts: non small cell lung cancer (NSCLC) diagnosed in 1999 in Manitoba and advanced NSCLC patients from the NCIC-CTG BR.18 trial. In the Manitoba cohort assessable tissue samples available in 79 patients (32 females and 47 males) and the majority (75%) had early stage disease. Fifty-one percent of patients expressed high levels of ER-beta (defined by >=60, the median immunohistochemistry score) and its expression was comparable in males and females. The 3-year overall survival of the group was 53% and males had significantly worse survival compared to females (HR=2.37, 95%CI 1.15-4.91, P=0.02). Higher ER-beta 1 expression was associated with better survival in both univariate (HR=0.41, 95%CI 0.21-0.80, P=0.009) and in multivariate (HR=0.37, 95%CI 0.18-0.77, P=0.008) analysis. In the NCIC-CTG cohort that were more often later stage, assessable tissue samples from 48 cases were available however higher ER beta 1 expression correlated with poorer survival (HR= 1.94, 95%CI 1.01-3.75 P=0.047). These results suggest a differential impact of ER-beta 1 expression on clinical outcome by disease stage, that needs to be explored further and may explain contradictory observations reported in the literature. PMID- 22302353 TI - Regulation of complement factor H (CFH) by multiple miRNAs in Alzheimer's disease (AD) brain. AB - Human brain cells rely on a specific subset of microRNAs (miRNAs or miRs) to shape their gene expression patterns, and this is mediated through microRNA effects on messenger RNA (mRNA) speciation and complexity. In recent studies (a) in short post-mortem interval Alzheimer's disease (AD) brain tissues versus age matched controls, and (b) in pro-inflammatory cytokine- and Abeta42 peptide stressed human neuronal-glial (HNG) cells in primary culture, we have identified several brain-abundant miRNA species found to be significantly up-regulated, including miR-125b and miR-146a. Both of these nuclear factor kappa B (NF-kappaB) activated, 22 nucleotide small non-coding RNAs (sncRNAs) target the mRNA of the key, innate-immune- and inflammation-related regulatory protein, complement factor-H (CFH; chr 1q32), resulting in significant decreases in CFH expression (p < 0.01, ANOVA). Our results further indicate that HNG cells respond to IL-1beta + Abeta42-peptide-induced stress by significant NF-kappaB-modulated up-regulation of miRNA-125b- and miRNA-146a. The complex interactive signaling of NF-kappaB, miR-125b, miR-146a, and perhaps other miRNAs, further illustrate interplay between inducible transcription factors and multiple pro-inflammatory sncRNAs that regulate CFH expression. The novel concept of miRNA actions involving mRNA target convergence and divergence are proposed and discussed. The combinatorial use of NF-kB inhibitors with anti-miRNAs (AMs; antagomirs) may have potential against CFH-driven pathogenic signaling in neurodegenerative disease, and may redirect our therapeutic perspectives to novel treatment strategies that have not yet been considered. PMID- 22302354 TI - Factors affecting clinician educator encouragement of routine HIV testing among trainees. AB - BACKGROUND: Adoption of CDC recommendations for routine, voluntary HIV screening of all Americans age 13-64 years has been slow. One method to increase adherence to clinical practice guidelines is through medical school and residency training. OBJECTIVE: To explore the attitudes, barriers, and behaviors of clinician educators (CEs) regarding advocating routine HIV testing to their trainees. DESIGN/PARTICIPANTS: We analyzed CE responses to a 2009 survey of Society of General Internal Medicine members from community, VA, and university-affiliated clinics regarding HIV testing practices. MAIN MEASURES: Clinician educators were asked about their outpatient practices, knowledge and attitudes regarding the revised CDC recommendations and whether they encouraged trainees to perform routine HIV testing. Associations between HIV testing knowledge and attitudes and encouraging trainees to perform routine HIV testing were estimated using bivariate and multivariable logistic regression. RESULTS: Of 515 respondents, 367 (71.3%) indicated they supervised trainees in an outpatient general internal medicine clinic. These CEs demonstrated suboptimal knowledge of CDC guidelines and over a third reported continued risk-based testing. Among CEs, 196 (53.4%) reported that they encourage trainees to perform routine HIV testing. Higher knowledge scores (aOR 5.10 (2.16, 12.0)) and more positive attitudes toward testing (aOR 8.83 (4.21, 18.5)) were independently associated with encouraging trainees to screen for HIV. Reasons for not encouraging trainees to screen included perceived low local prevalence (37.2%), competing teaching priorities (34.6%), and a busy clinic environment (34.0%). CONCLUSIONS: Clinician educators have a special role in the dissemination of the CDC recommendations as they impact the knowledge and attitudes of newly practicing physicians. Despite awareness of CDC recommendations, many CEs do not recommend universal HIV testing to trainees. Interventions that improve faculty knowledge of HIV testing recommendations and address barriers in resident clinics may enhance adoption of routine HIV testing. PMID- 22302355 TI - Enhancing care for hospitalized older adults with cognitive impairment: a randomized controlled trial. AB - BACKGROUND: Approximately 40% of hospitalized older adults have cognitive impairment (CI) and are more prone to hospital-acquired complications. The Institute of Medicine suggests using health information technology to improve the overall safety and quality of the health care system. OBJECTIVE: Evaluate the efficacy of a clinical decision support system (CDSS) to improve the quality of care for hospitalized older adults with CI. DESIGN: A randomized controlled clinical trial. SETTING: A public hospital in Indianapolis. POPULATION: A total of 998 hospitalized older adults were screened for CI, and 424 patients (225 intervention, 199 control) with CI were enrolled in the trial with a mean age of 74.8, 59% African Americans, and 68% female. INTERVENTION: A CDSS alerts the physicians of the presence of CI, recommends early referral into a geriatric consult, and suggests discontinuation of the use of Foley catheterization, physical restraints, and anticholinergic drugs. MEASUREMENTS: Orders of a geriatric consult and discontinuation orders of Foley catheterization, physical restraints, or anticholinergic drugs. RESULTS: Using intent-to-treat analyses, there were no differences between the intervention and the control groups in geriatric consult orders (56% vs 49%, P = 0.21); discontinuation orders for Foley catheterization (61.7% vs 64.6%, P = 0.86); physical restraints (4.8% vs 0%, P = 0.86), or anticholinergic drugs (48.9% vs 31.2%, P = 0.11). CONCLUSION: A simple screening program for CI followed by a CDSS did not change physician prescribing behaviors or improve the process of care for hospitalized older adults with CI. PMID- 22302356 TI - Inappropriate Medication in Home Health Care. PMID- 22302357 TI - From the Editors' Desk: Improving Performance Through Coaching, Incentives, Feedback, and Practice. PMID- 22302358 TI - Communication and behavior change challenges to limiting the development of antibiotic resistance. PMID- 22302359 TI - Morality in the valley of the moon: The origins of the ethics of neonatal intensive care. AB - One of the first areas of ethical concern in medicine was the neonatal intensive care unit. Questions first seen in this context soon entered the discourse of bioethical debate. The history of the ethics of neonatal care is described from the context of neonatology, and the emerging principles are outlined. PMID- 22302360 TI - The basics of western blotting. PMID- 22302361 TI - Evaluation of metabolic syndrome after hematopoietic stem cell transplantation in children and adolescents. AB - BACKGROUND: To determine the prevalence, characteristics, and risk factors associated with metabolic syndrome (MS) in patients undergoing hematopoietic stem cell transplantation (HSCT) in the Chilean National Program. PROCEDURES: Descriptive and cross-sectional study including 69 patients was conducted. Body mass index, pubertal development, waist circumference, arterial pressure (AP), and triglycerides, HDL-cholesterol, and glucose levels were recorded at the time of study entry. The National Cholesterol Education Program (Adult Treatment Panel III, as modified by the American Heart Association) criteria are often used to diagnose MS in adults; however, for children and adolescents we followed criteria according to De Ferranti and American Diabetes Association. Statistical analyses were performed with a chi-square test or Fisher's exact test according to sample size. RESULTS: Sixty-nine patients were studied. The median age at the time of diagnosis was 12.9 years, and the median time of follow-up post-transplant was 4 years. Forty-three patients were males, 54 patients had malignant diseases, and 59 patients received allogeneic transplants. Of the 69 patients, 32% had MS; the most common MS features were abdominal obesity (73%), hypertriglyceridemia (91%), and a low HDL-cholesterol level (96%). The most significant risk factor for MS was corticosteroid therapy use pre- (P < 0.03) and post-HSCT (P < 0.03), obesity and overweight associated with MS (P < 0.001). No patient developed cardiovascular complications. CONCLUSIONS: The prevalence of MS was 32%, which was significantly higher than in a healthy pediatric population. We recommend prolonged follow-up for transplant recipients, coupled with enforcement of preventive measures, such as early diagnosis and encouragement of a healthy lifestyle. PMID- 22302362 TI - The neutral-niche debate: a philosophical perspective. PMID- 22302363 TI - Influence of sparkle and saccades on tongue electro-stimulation-based vision substitution of 2D vectors. AB - Vision substitution by electro-stimulation has been studied since the 60s beginning with P. Bach-y-Rita. Camera pictures or movies encoded in gray levels are displayed using an electro-stimulation display device on the surface of a body part, such as the skin or the tongue. Medical-technical devices have been developed on this principle to compensate for sensory-motor disabilities such as blindness or loss of balance, or to guide specific actions, such as surgery. However, the electrical signals of stationary or moving slowly moving objects, displayed on a Tongue display unit (TDU), are quickly lost due to saturation of receptors undergoing electrostimulation. We propose to add random saccades or sparkle to the displayed visual scene to increase the quality of pattern recognition by the subjects. In the present experimental trimodal study (normal vision, TDU vision substitution, or both), we show that the presence of a moderate sparkle level enhances the perception of the direction of lines drawn on a TDU and reduces the response time. PMID- 22302364 TI - Site-selective radiolabeling of peptides by (18)F-fluorobenzoylation with [(18F)]SFB in solution and on solid phase: a comparative study. AB - Peptides labeled with short-lived positron-emitting radionuclides are of outstanding interest as probes for molecular imaging by positron emission tomography (PET). Herein, the site-selective incorporation of fluorine-18 into lysine-containing peptides using the prosthetic labeling agent N-succinimidyl 4 [(18)F]fluorobenzoate ([(18)F]SFB) is described. The reaction of [(18)F]SFB with four biologically relevant resin-bound peptides was studied and optimized. For comparison, each peptide was 18F-fluorobenzoylated in solution under different conditions and the product distribution was analyzed confirming the advantages of the solid-phase approach. The method's feasibility for selective radiolabeling either at the N-terminus or at the lysine side chain was demonstrated. Labeling on solid phase with [(18)F]SFB resulted in crude (18)F-fluorobenzoylpeptides whose radiochemical purities were typically greater than 90% and that could be prepared in synthesis times from 65 to 76 min. PMID- 22302365 TI - Taurine ameliorates alloxan-induced diabetic renal injury, oxidative stress related signaling pathways and apoptosis in rats. AB - Hyperglycemia-induced oxidative stress plays a vital role in the progression of diabetic nephropathy. The renoprotective nature of taurine has also been reported earlier; but little is known about the mechanism of this beneficial action. The present study has, therefore, been carried out to explore in detail the mechanism of the renoprotective effect of taurine under diabetic conditions. Diabetes was induced in rats by alloxan (single i.p. dose of 120 mg/kg body weight) administration. Taurine was administered orally for 3 weeks (1% w/v in drinking water) either from the day on which alloxan was injected or after the onset of diabetes. Alloxan-induced diabetic rats showed a significant increase in plasma glucose, enhanced the levels of renal damage markers, plasma creatinine, urea nitrogen and urinary albumin. Diabetic renal injury was associated with increased kidney weight to body weight ratio and glomerular hypertrophy. Moreover, it increased the productions of reactive oxygen species, enhanced lipid peroxidation and protein carbonylation in association with decreased intracellular antioxidant defense in the kidney tissue. In addition, hyperglycemia enhanced the levels of proinflammatory cytokins (TNF-alpha, IL-6, IL-1beta) and Na(+)--K(+)-ATPase activity with a concomitant reduction in NO content and eNOS expression in diabetic kidney. Investigation of the oxidative stress-responsive signaling cascades showed the upregulation of PKCalpha, PKCbeta, PKCepsilon and MAPkinases in the renal tissue of the diabetic animals. However, taurine administration decreased the elevated blood glucose and proinflammatory cytokine levels, reduced renal oxidative stress (via decrease in xanthine oxidase activity, AGEs formation and inhibition of p47phox/CYP2E1 pathways), improved renal function and protected renal tissue from alloxan-induced apoptosis via the regulation of Bcl-2 family and caspase-9/3 proteins. Taurine supplementation in regular diet could, therefore, be beneficial to regulate diabetes-associated renal complications. PMID- 22302366 TI - Antidepressant effect of taurine in diabetic rats. AB - Clinical and preclinical studies have shown that diabetic individuals present more depressive behaviors than non-diabetic individuals. Taurine, one of the most abundant free amino acids in the central nervous system, modulates a variety of biological functions and acts as an agonist at GABAA receptors. Our objective was to assess the antidepressant effect of taurine in diabetic rats. Additionally, we studied the effect of taurine on weight gain, water and food intake, and blood glucose levels in diabetic and non-diabetic rats. Male Wistar rats were divided into control (CTR) and streptozotocin-induced diabetic (STZ) groups and were administered daily 0, 25, 50 or 100 mg/kg of taurine (n = 10 per subgroup) intraperitoneally. After 28 days of treatment, the animals were exposed to the forced swimming test, and their behaviors were recorded. Weight gain, water and food intake, and blood glucose levels were measured weekly. Our results showed that STZ rats had a higher immobility duration than CTR rats, and taurine decreased this depressive-like behavior in STZ rats at doses of 25 and 100 mg/kg. Both of these doses of taurine also decreased water intake and improved weight gain in STZ rats. All doses of taurine decreased the water intake in CTR rats. Taurine, at a dose of 100 mg/kg, decreased food intake and blood glucose levels in STZ rats. Because taurine is a GABA agonist and both amino acids are lower in the plasma of diabetic and depressive individuals, we hypothesize that taurine may represent a new adjuvant drug for the treatment of depression in diabetic individuals. PMID- 22302367 TI - Non-canonical interactions of porphyrins in porphyrin-containing proteins. AB - In this study we have described the noncanonical interactions between the porphyrin ring and the protein part of porphyrin-containing proteins to better understand their stabilizing role. The analysis reported in this study shows that the predominant type of non-canonical interactions at porphyrins are CH....O and CH....N interactions, with a small percentage of CH...pi and noncanonical interactions involving sulfur atoms. The majority of non-canonical interactions are formed from side-chains of charged and polar amino acids, whereas backbone groups are not frequently involved. The main-chain noncanonical interactions might be slightly more linear than the side-chain interactions, and they have somewhat shorter median distances. The analysis, performed in this study, shows that about 44% of the total interactions in the dataset are involved in the formation of multiple (furcated) noncanonical interactions. The high number of porphyrin-water interactions show importance of the inclusion of solvent in protein-ligand interaction studies. Furthermore, in the present study we have observed that stabilization centers are composed predominantly from nonpolar amino acid residues. Amino acids deployed in the environment of porphyrin rings are deposited in helices and coils. The results from this study might be used for structure-based porphyrin protein prediction and as scaffolds for future porphyrin-containing protein design. PMID- 22302368 TI - Transglutaminases: key regulators of cancer metastasis. AB - The ability to metastasize represents the most important characteristic of malignant tumors. The biological details of the metastatic process remain somewhat unknown, due to difficulties in studying tumor cell behaviour with high spatial and temporal resolution in vivo. Several lines of evidence involve transglutaminases (TGs) in the key stages of tumor progression cascade, even though the molecular mechanisms remain controversial. TG expression and activity display a different role in the primary tumor or in metastatic cells. In fact, TG expression is low in the primary tumor mass, but augmented when cells acquire the metastatic phenotype. Nevertheless, in other cases, the use of inducers of TG transamidating activity seems to contrast tumor cell plasticity, migration and invasion. In the following review, the function of TGs in cancer cell migration into the extracellular matrix, adhesion to the capillary endothelium and its basement membrane, invasion and angiogenesis is discussed. PMID- 22302370 TI - Carbon dynamics in trees: feast or famine? AB - Research on the degree to which carbon (C) availability limits growth in trees, as well as recent trends in climate change and concurrent increases in drought related tree mortality, have led to a renewed focus on the physiological mechanisms associated with tree growth responses to current and future climate. This has led to some dispute over the role of stored non-structural C compounds as indicators of a tree's current demands for photosynthate. Much of the uncertainty surrounding this issue could be resolved by developing a better understanding of the potential functions of non-structural C stored within trees. In addition to functioning as a buffer to reconcile temporal asynchrony between C demand and supply, the storage of non-structural C compounds may be under greater regulation than commonly recognized. We propose that in the face of environmental stochasticity, large, long-lived trees may require larger C investments in storage pools as safety margins than previously recognized, and that an important function of these pools may be to maintain hydraulic transport, particularly during episodes of severe stress. If so, survival and long-term growth in trees remain a function of C availability. Given that drought, freeze-thaw events and increasing tree height all impose additional constraints on vascular transport, the common trend of an increase in non-structural carbohydrate concentrations with tree size, drought or cold is consistent with our hypothesis. If the regulated maintenance of relatively large constitutive stored C pools in trees serves to maintain hydraulic integrity, then the minimum thresholds are expected to vary depending on the specific tissues, species, environment, growth form and habit. Much research is needed to elucidate the extent to which allocation of C to storage in trees is a passive vs. an active process, the specific functions of stored C pools, and the factors that drive active C allocation to storage. PMID- 22302369 TI - Induction of NAD(P)H:quinone oxidoreductase 1 expression by cysteine via Nrf2 activation in human intestinal epithelial LS180 cells. AB - In this study, we examined the effects of 20 amino acids on the expression level of NAD(P)H:quinone oxidoreductase 1 (NQO1) in human intestinal LS180 cells. Five amino acids were associated with significant increases in NQO1 mRNA expression; the most substantial increase was induced by cysteine, which markedly increased the NQO1 mRNA level in a time- and dose-dependent manner. Cysteine also increased the protein level of NQO1 and its enzymatic activity in LS180 cells. Furthermore, cysteine significantly up-regulated NQO1 promoter activity, and this induction was completely abolished by mutation of the antioxidant response element, a binding site of the nuclear factor erythroid 2-related factor 2 (Nrf2). Knockdown experiment using siRNA against Nrf2 showed the involvement of Nrf2 on cysteine induced increase in NQO1 mRNA expression. Further, cysteine treatment increased the amount of Nrf2 protein in the nucleus and decreased the amount of Kelch-like ECH-associated protein 1 (a suppressor protein of Nrf2) in the cytosol, suggesting that Nrf2 was activated by cysteine. Oral administration of cysteine to mice significantly increased NQO1 mRNA levels in the mouse intestinal mucosa. These findings show that cysteine induces NQO1 expression in both in vitro and in vivo systems and also suggest that Nrf2 activation is involved in this induction. PMID- 22302371 TI - Survival data analyses in ecotoxicology: critical effect concentrations, methods and models. What should we use? AB - In ecotoxicology, critical effect concentrations are the most common indicators to quantitatively assess risks for species exposed to contaminants. Three types of critical effect concentrations are classically used: lowest/ no observed effect concentration (LOEC/NOEC), LC( x) (x% lethal concentration) and NEC (no effect concentration). In this article, for each of these three types of critical effect concentration, we compared methods or models used for their estimation and proposed one as the most appropriate. We then compared these critical effect concentrations to each other. For that, we used nine survival data sets corresponding to D. magna exposition to nine different contaminants, for which the time-course of the response was monitored. Our results showed that: (i) LOEC/NOEC values at day 21 were method-dependent, and that the Cochran-Armitage test with a step-down procedure appeared to be the most protective for the environment; (ii) all tested concentration-response models we compared gave close values of LC50 at day 21, nevertheless the Weibull model had the lowest global mean deviance; (iii) a simple threshold NEC-model both concentration and time dependent more completely described whole data (i.e. all timepoints) and enabled a precise estimation of the NEC. We then compared the three critical effect concentrations and argued that the use of the NEC might be a good option for environmental risk assessment. PMID- 22302372 TI - Ab initio protein modeling into CryoEM density maps using EM-Fold. AB - EM-Fold was used to build models for nine proteins in the maps of GroEL (7.7 A resolution) and ribosome (6.4 A resolution) in the ab initio modeling category of the 2010 cryo-electron microscopy modeling challenge. EM-Fold assembles predicted secondary structure elements (SSEs) into regions of the density map that were identified to correspond to either alpha-helices or beta-strands. The assembly uses a Monte Carlo algorithm where loop closure, density-SSE length agreement, and strength of connecting density between SSEs are evaluated. Top-scoring models are refined by translating, rotating, and bending SSEs to yield better agreement with the density map. EM-Fold produces models that contain backbone atoms within SSEs only. The RMSD values of the models with respect to native range from 2.4 to 3.5 A for six of the nine proteins. EM-Fold failed to predict the correct topology in three cases. Subsequently, Rosetta was used to build loops and side chains for the very best scoring models after EM-Fold refinement. The refinement within Rosetta's force field is driven by a density agreement score that calculates a cross-correlation between a density map simulated from the model and the experimental density map. All-atom RMSDs as low as 3.4 A are achieved in favorable cases. Values above 10.0 A are observed for two proteins with low overall content of secondary structure and hence particularly complex loop modeling problems. RMSDs over residues in secondary structure elements range from 2.5 to 4.8 A. PMID- 22302373 TI - Kinetics of blood CD34(+) cells after chemotherapy plus G-CSF in poor mobilizers: implications for pre-emptive plerixafor use. AB - Mobilization and collection of stem cells is difficult in a proportion of patients intended for autologous stem cell transplantation (ASCT). We have evaluated mobilization kinetics of blood CD34(+) cells (B-CD34(+)) to form basis for algorithm to facilitate rational pre-emptive plerixafor use. Altogether 390 chemomobilized patients were included.Forty-three patients (11%) did not reach BCD34+count >=10*10(6)/l. Mobilization kinetics differed according to the mobilization capacity observed. Among those who were very poor or inadequate mobilizers (peak BCD34(+)count <=5*10(6)/l and 6-10*10(6)/l, respectively), BCD34+counts rarely rose after white blood cells (WBC) >5-10*10(9)/l, whereas in many standard mobilizers a later rise in CD34(+) counts could be observed. Four algorithms based on WBC and CD34(+) counts were constructed. According to this patient series, algorithm II (WBC >5*109/l and BCD34+<=10*10(6)/l) and algorithm IV (WBC >10*10(9)/l andB-CD34(+) <=10*10(9)/l) were the most applicable. For algorithm II the sensitivity was 0.97 and specificity 1.00, respectively, to identify patients for plerixafor use provided that all patients with B-CD34+ maximum <=10*10(6)/l would have needed plerixafor.This simple model needs a prospective validation. PMID- 22302374 TI - The clinical significance of vancomycin minimum inhibitory concentration in Staphylococcus aureus infections: a systematic review and meta-analysis. AB - BACKGROUND: Emerging data suggest that vancomycin may be less effective against serious methicillin-resistant Staphylococcus aureus (MRSA) infections with minimum inhibitory concentration (MIC) values at the higher end of the susceptibility range. The purpose of this review is to examine the strength of these associations. METHODS: All relevant studies pertaining to treatment outcomes or mortality associated with vancomycin MIC were retrieved from the medical literature from January 1996 through August 2011 and analyzed according to Cochrane guidelines. RESULTS: Of the 270 studies identified, 48 studies were reviewed, with 22 studies included in the final meta-analysis. Vancomycin MIC was significantly associated with mortality for MRSA infection irrespective of the source of infection or MIC methodology (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.14-2.37; P < .01). This mortality association was predominantly driven by bloodstream infections (BSIs; OR, 1.58; 95% CI, 1.06-2.37; P = .03) and isolates with a vancomycin MIC of 2 MUg/mL by Etest (OR, 1.72; 95% CI, 1.34-2.21; P < .01). Vancomycin MIC was significantly associated with treatment failure irrespective of source of infection or MIC methodology (OR, 2.69; 95% CI, 1.60 4.51; P < .01). CONCLUSION: High vancomycin MIC was associated with a higher mortality rate in MRSA BSI. Thus, institutions should consider conducting Etest MICs on all MRSA BSI isolates. Although these data highlight concerns about vancomycin, currently, there are no data to support better survival rates with alternative antibiotics. Data are sorely needed to determine whether other agents can remedy these outcomes observed with vancomycin for MRSA infections with elevated vancomycin MIC values. PMID- 22302375 TI - Methicillin-resistant Staphylococcus aureus and vancomycin: minimum inhibitory concentration matters. PMID- 22302376 TI - Serum-free culture of an embryonic cell line from Bombyx mori and reinforcement of susceptibility of a recombinant BmNPV by cooling. AB - We established the first continuous cell line that uses a serum-free culture from the embryo of Bombyx mori (Lepidoptera: Bombycidae), designated as NIAS-Bm-Ke17. This cell line was serially subcultured in the SH-Ke-117 medium. The cells adhere weakly to the culture flask, and most cells have an oval shape. The cell line was subcultured 154 times, and the population doubling time is 83.67+/-5.22 h. Random amplification of polymorphic DNA-polymerase chain reaction with a tenmar single primer for discrimination of insect cell lines recognized the NIAS-Bm-Ke1 cell line as B. mori. This cell line does not support the growth of the B. mori nuclear polyhedrosis virus (BmNPV) in the absence of the heat-inactivated hemolymph of B. mori. However, the heat-inactivated hemolymph in 1% volume of the medium supported a high level of susceptibility to BmNPV. In addition, the cooling treatment of the cells at 2.5 degrees C also enhanced the susceptibility. We report a new serum-free culture system of the B. mori cell line for the baculovirus expression vector system. PMID- 22302377 TI - The effect of acute exercise with increasing workloads on inactive muscle blood flow and its heterogeneity in humans. AB - The distribution of blood flow between active and inactive skeletal muscles has been sparsely studied in humans. Here we investigated non-exercising leg blood flow in six healthy young women during intermittent isometric one leg knee extension exercise with increasing workloads. Positron emission tomography was used to measure blood flow in hamstring muscles of the exercising leg, and whole thigh muscles as well as its knee extensor and hamstring compartment of the resting leg. Mean blood flow to the hamstrings of the exercising leg (5.8 +/- 2.6 ml/100 g/min during the highest exercise workload) and whole thigh muscle of the resting leg (7.1 +/- 3.8 ml/100 g/min) did not change significantly from rest (4.0 +/- 0.7 and 4.7 +/- 1.9 ml/100 g/min, respectively) to exercise, but flow heterogeneity increased substantially at increasing workloads. Importantly, during the highest exercise workload, mean blood flow in the knee extensors of the resting leg decreased (5.5 +/- 3.0 ml/100 g/min at rest and 3.4 +/- 2.0 ml/100 g/min during exercise, p < 0.01) while flow heterogeneity increased (28 +/ 8% at rest and 83 +/- 26% during exercise, p < 0.05). Conversely, in hamstring muscles of the resting leg blood flow increased from 3.9 +/- 1.0 ml/100 g/min at rest to 11.5 +/- 6.8 ml/100 g/min during exercise (p < 0.05) while flow heterogeneity increased from 30 +/- 7 to 58 +/- 19% (p < 0.05). In conclusion, while mean whole thigh muscle blood flow of the resting leg remains at resting level during one leg exercise of the contralateral leg, redistribution of blood flow between muscle parts occurs within the thigh. Based on previous studies, nervous constraints most probably act to cause this blood flow distribution. PMID- 22302378 TI - The determinants of performance in master swimmers: an analysis of master world records. AB - Human performances in sports decline with age in all competitions/disciplines. Since the effects of age are often compounded by disuse, the study of master athletes provides the opportunity to investigate the effects of age per se on the metabolic/biomechanical determinants of performance. For all master age groups, swimming styles and distances, we calculated the metabolic power required to cover the distance (d) in the best performance time as: E' maxR 1/4 C d=BTP 1/4 C vmax; where C is the energy cost of swimming in young elite swimmers, vmax = d/BTP is the record speed over the distance d, and BTP was obtained form "cross sectional data" (http://www.fina.org). To establish a record performance, E' maxR must be equal to the maximal available metabolic power (E'maxA). This was calculated assuming a decrease of 1% per year at 40 - 70 years, 2% at 70 - 80 years and 3% at 80 - 90 years (as indicated in the literature) and compared to the E' maxR values, whereas up to about 55 years of age E' maxR 1/4 E' maxA; for older subjects E' maxA > E' maxR; the difference increasing linearly by about 0.30% (backstroke), 1.93% (butterfly), 0.92% (front crawl) and 0.37% (breaststroke) per year (average over the 50, 100 and 200 m distances). These data suggest that the energy cost of swimming increases with age. Hence, the decrease in performance in master swimmers is due to both decrease in the metabolic power available (E' maxA) and to an increase in C. PMID- 22302379 TI - [Complete immunization coverage and reasons for non-vaccination in a periurban area of Abidjan]. AB - An immunization coverage survey was conducted among children aged 12-59 months in a suburban neighbourhood in Abidjan. The objective was to determine the complete immunization coverage, the reasons for non-vaccination and factors influencing the immunization status of children. The method of exhaustive sampling enabled us to interview the mothers of 669 children using a questionnaire. Overall vaccination coverage was 68.6% with 1.2%, with 1.2% of children never having received vaccine. The logistic regression analysis showed that the level of education, knowledge of the immunization schedule and the marital status of mothers, as well as the type of habitat, were associated with full immunization of children. These determinants must be taken into account to improve vaccination coverage. PMID- 22302380 TI - [Hospitalization rates for immigrant-related illness among individuals with low income and full health insurance coverage in France, 2009]. AB - Complementary Universal Health Insurance (CMUC) which provides free access to health care has been available in France since 2000 for people with an annual income less than 60% of the poverty threshold. Hospitalization rates in 2009 for common diseases among immigrants were compared between beneficiaries of the general scheme under the age of 60 years with (4.5 millions) or without CMUC (34.1 millions) in 2008 and still alive at the end of the year. Data were derived from the French national health insurance reimbursements and short-stay hospital discharge databases. Age - and sex-adjusted hospitalization rates and relative risk significantly greater overall hospitalization rates (17.5% vs 13.2%) (males RR= 2.0, female RR 2.3) and each parasitic diseases (RR = 2.1), which include viral diseases and fevers of unknown origin (1.1/1000, RR =1.6), septicaemia (0.4/1000, RR = 2.2), HIV infection (0.7/1000, RR = 3.5), other infectious and parasitic diseases (0.7/1000, RR= 2.5) and, more precisely, measles (2.7/1000, RR = 5.0). Hospitalization for sickle cell disease (3%, RR = 4.5) were also more frequent as also for lead poisoning (0.12/1000, RR = 5.2). In this low-income population with free access to health care, hospitalizations were higher for many diseases that are targets for prevention and screening actions. This is tha case for immigrant with CMUC coverage arriving in France and when they travel to their country of origin. PMID- 22302381 TI - [Haitian women living with HIV/AIDS in Guadeloupe: pregnancy between medical stakes, social benefits and administrative vulnerability. A qualitative study]. AB - Guadeloupe (French West Indies) is a part of French departments which has the large number of persons living with HIV/AIDS. A large part of them consists of foreign women, mainly native of Haiti. This article is based on an anthropological study conducted in 2009 among professionals of health, social and associative sectors taking care of persons living with HIV in Guadeloupe, and among 10 infected women, 6 of them are native of Haiti. Semi-directive and individual qualitative interviews were conducted with each of these persons. During their course of illness and migration, many women experienced one or several pregnancies. The analysis of their discourses and trajectories underlines the articulation of the multiple stakes - medical, social, political, emotional stakes - with which they are confronted. PMID- 22302382 TI - Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. PMID- 22302383 TI - Functional silk: colored and luminescent. AB - Silkworm silk is among the most widely used natural fibers for textile and biomedical applications due to its extraordinary mechanical properties and superior biocompatibility. A number of physical and chemical processes have also been developed to reconstruct silk into various forms or to artificially produce silk-like materials. In addition to the direct use and the delicate replication of silk's natural structure and properties, there is a growing interest to introduce more new functionalities into silk while maintaining its advantageous intrinsic properties. In this review we assess various methods and their merits to produce functional silk, specifically those with color and luminescence, through post-processing steps as well as biological approaches. There is a highlight on intrinsically colored and luminescent silk produced directly from silkworms for a wide range of applications, and a discussion on the suitable molecular properties for being incorporated effectively into silk while it is being produced in the silk gland. With these understanding, a new generation of silk containing various functional materials (e.g., drugs, antibiotics and stimuli-sensitive dyes) would be produced for novel applications such as cancer therapy with controlled release feature, wound dressing with monitoring/sensing feature, tissue engineering scaffolds with antibacterial, anticoagulant or anti inflammatory feature, and many others. PMID- 22302384 TI - Does additional confounder information alter the estimated risk of bleeding associated with phenprocoumon use--results of a two-phase study. AB - PURPOSE: Claims databases are an important source for pharmacoepidemiological studies although they often lack information on some confounders. Two-phase methodology was used to estimate the bleeding risk in patients treated with phenprocoumon from claims data combined with additional information on body mass index (BMI) and smoking. METHODS: We conducted a nested case-control study using claims data from 2004 to 2007 (phase 1). Additional information was obtained from interviews in a subset of 505 insurants (phase 2). Adjusted bleeding OR were calculated using logistic regression using data from the complete case-control dataset. Furthermore, a two-phase analysis was conducted, taking into consideration phase 2 data on BMI and smoking. RESULTS: The phase 1 sample included 1248 cases and 24,960 controls. In phase 1, we observed an adjusted bleeding ORs of 3.93 (95%CI: 2.75-5.61) for male subjects aged 55 years taking phenprocoumon. The bleeding risk associated with phenprocoumon use decreased with increasing age. The two-phase analysis revealed smoking and a high BMI as risk factors for bleeding. The OR for phenprocoumon obtained from the two-phase analysis was of similar size as the phase 1 estimate. DISCUSSION: Phase 2 data added valuable information on smoking and BMI. However, phase 1 results did not change dramatically after accounting for phase 2 information, which is reassuring for the validity of database studies. PMID- 22302385 TI - Evaluation of cardiovascular risk in patients with rheumatoid arthritis: do cardiovascular biomarkers offer added predictive ability over established clinical risk scores? AB - OBJECTIVE: To determine whether adding C-reactive protein, anti-cyclic citrullinated peptide antibodies, rheumatoid factor, N-terminal pro-brain natriuretic peptide (NT-proBNP), oxidized low-density lipoprotein (ox-LDL), or anti-apolipoprotein A-I (anti-Apo A-I) IgG to the Framingham 10-year cardiovascular (CV) risk score (FRS) could improve its CV prognostic accuracy in rheumatoid arthritis (RA). METHODS: We performed an ancillary study derived from a prospective single-center cohort consisting of 118 RA patients without CV disease at baseline. The FRS and the various biomarkers were assessed at enrollment and their prognostic accuracy was determined using receiver operating characteristic (ROC) curve analysis. The incremental predictive ability of biomarkers was assessed using the integrated discrimination improvement (IDI) statistics. RESULTS: During a median followup period of 9 years, the incidence of CV events was 16%. Both the FRS and 3 of the biomarkers (NT-proBNP, ox-LDL, and anti-Apo A-I) were significant predictors of subsequent CV events (area under the ROC curve [AUC] between 0.68 and 0.73). Anti-Apo A-I was the only biomarker to significantly improve the prognostic ability of the FRS, with AUCs increasing from 0.72 to 0.81 and the IDI improving by 175% (P < 0.001). CONCLUSION: Among the biomarkers tested, only anti-Apo A-I significantly improved the FRS predictive ability. PMID- 22302386 TI - Population-based review of tetralogy of Fallot with absent pulmonary valve: is prenatal diagnosis really associated with a poor prognosis? AB - OBJECTIVES: Tetralogy of Fallot with absent pulmonary valve syndrome (TETAPV) is reported in obstetric literature to have an extremely poor prognosis. We sought to determine the clinical outcome associated with TETAPV and whether prenatal diagnosis confers a poor prognosis. METHODS: All cases of TETAPV diagnosed in British Columbia between 1980 and 2009 were reviewed and grouped according to time of diagnosis, either prenatal or postnatal. The groups were compared with respect to mortality, respiratory problems, number of interventions and functional capacity at last follow-up. RESULTS: Eight and 11 patients were included in the prenatally and postnatally diagnosed groups, with overall long term survival of 71% and 82%, respectively. There was no significant difference in mortality, frequency of preoperative intubation, number of interventions or functional capacity between groups. CONCLUSION: From a population-based retrospective analysis of TETAPV cases identified over three decades it is concluded that the prognosis for TETAPV is better than that previously reported in the obstetric literature. This information should be used to guide prenatal counseling. PMID- 22302387 TI - The novel 172 sheep (Ovis aries) microRNAs and their targets. AB - MicroRNAs (miRNAs) are small, non-coding and regulatory RNAs about ~22 nucleotides in length. The comparative genomics approach due to their conserved nature is a good source for the novel miRNAs discovery. In this study, total 172 novel miRNAs from 140 precursor sequences belonging to 114 families were identified in sheep (Ovis aries), the most important livestock animal. All the miRNA families (oar-mir-95, 129, 130, 186, 214, 219, 223, 324, 339, 423, 450, 499, 544, 562, 568, 584, 669, 671, 763, 935, 1281, 1282, 1306, 1552, 1584, 1587, 1603, 1607, 1706, 1711, 1718, 1732, 1738, 1761, 1771, 1777, 1778, 1780, 1807, 1843, 1895, 1930, 2127, 2139, 2182, 2284, 2287, 2295, 2296, 2310, 2311, 2314, 2315, 2316, 2320, 2359, 2378, 2381, 2382, 2395, 2400, 2404, 2410, 2412, 2423, 2426, 2435, 2470, 2477, 2482, 2487, 2881, 2883, 2885, 2888, 2889, 2896, 2901, 2904, 2917, 2964, 3063, 3064, 3074, 3080, 3432, 3529, 3533, 3613, 3649, 3654, 3658, 3661, 3662, 3940, 3960, 4273, 4426, 4447, 4459, 4468, 4493, 4507, 4647, 4680, 4785, 4788, 4800, 5102, 5105, 5109, 5115, 5125 and 5132) are found for the first time in Sheep. All 140 miRNA precursors form stable minimum free energy stem loop and the mature miRNAs reside in the stem portion of the stem loop structure. Their putative targets are involved in transcription factors (26%), signaling (19%), metabolism (18%), transportation (10%), immunity (9%), cancer and tumor related (5%), growth and development (5%), stress related (4%), and structural proteins (3%). PMID- 22302388 TI - Systematic analysis of plant-specific B3 domain-containing proteins based on the genome resources of 11 sequenced species. AB - B3 domain-containing proteins constitute a large transcription factor superfamily. The plant-specific B3 superfamily consists of four family members, i.e., LAV (LEC2 [LEAFY COTYLEDON 2]/ABI3 [ABSCISIC ACID INSENSITIVE 3] - VAL [VP1/ABI3-LIKE]), RAV (RELATED to ABI3/VP1), ARF (AUXIN RESPONSE FACTOR) and REM (REPRODUCTIVE MERISTEM) families. The B3 superfamily plays a central role in plant life, from embryogenesis to seed maturation and dormancy. In previous research, we have characterized ARF family, member of the B3 superfamily in silico (Wang et al., Mol Biol Rep, 2011, doi:10.1007/s11033-011-0991-z). In this study, we systematically analyzed the diversity, phylogeny and evolution of B3 domain-containing proteins based on genomic resources of 11 sequenced species. A total of 865 B3 domain-containing genes were identified from 11 sequenced species through an iterative strategy. The number of B3 domain-containing genes varies not only between species but between gene families. B3 domain-containing genes are unevenly distributed in chromosomes and tend to cluster in the genome. Numerous combinations of B3 domains and their partner domains contribute to the sequences and structural diversification of the B3 superfamiy. Phylogenetic results showed that moss VAL proteins are related to LEC2/ABI3 instead of VAL proteins from higher plants. Lineage-specific expansion of ARF and REM proteins was observed. The REM family is the most diversified member among the B3 superfamily and experiences a rapid divergence during selective sweep. Based on structural and phylogenetic analysis results, two possible evolutional modes of the B3 superfamily were presented. Results presented here provide a resource for further characterization of the B3 superfamily. PMID- 22302389 TI - Proteomic analysis of differentially expressed proteins in the lymphoid organ of Vibrio harveyi-infected Penaeus monodon. AB - The protein expression profiles of the lymphoid organ, taken from mock and systemic Vibrio harveyi-infected Penaeus monodon at 6 and 48 h post infection, were revealed. The considerable changes in the expression level of several proteins were observed between the mock and V. harveyi-infected shrimps. From 30 analyzed protein spots with 27 differentially expressed, 21 were known proteins with the most common of these being cytoskeleton proteins (33%) which were all down-regulated upon systemic bacterial infection. Other six proteins including four proteins that are involved in the shrimp immunity (alpha-2-macroglobulin, transglutaminase, heat shock protein 1 and hemocyanin subunit Y), and two proteins that are involved in metabolism (triosephosphate isomerase) and cell signaling (14-3-3 like protein), displayed significantly decreased expression levels. There was, however, an increase in the expression level of the ATP synthase beta subunit, a protein involved in energy balance. Transcription levels of ATP synthase beta subunit and 14-3-3 like protein were up- and down-regulated, respectively, in accord with the observed protein expression levels, but the alpha-2-macroglobulin transcript levels were significantly increased in contrast to the decreased protein expression levels. Interestingly, partial gene silencing of ATP synthase beta subunit revealed a high cumulative mortality of the knockdown shrimps (73.3%) and a dramatic reduction of the total hemocyte numbers in the survival shrimps. These altered proteins are likely to play essential roles in shrimp defense against the pathogenic bacterium V. harveyi. PMID- 22302390 TI - Diagnosis of mitochondrial disorders applying massive pyrosequencing. AB - Mitochondrial disorders are a frequent cause of neurological disability affecting children and adults. Traditionally, molecular diagnosis of mitochondrial diseases was mostly accomplished by the use of Sanger sequencing and PCR-RFLP. However, there are particular drawbacks associated with the use of these methods. Recent multidisciplinary advances have led to new sequencing methods that may overcome these limitations. Our goal was to explore the use of a next generation sequencing platform in the molecular diagnosis of mitochondrial diseases reporting our findings in adult patients that present with a clinical pathological diagnosis of a mitochondrial encephalomyopathy. Complete genomic sequences of mitochondrial DNA were obtained by 454 massive pyrosequencing from blood samples. The analysis of these sequences allowed us to identify two diagnostic pathogenic mutations and 74 homoplasmic polymorphisms, useful for obtaining high-resolution mitochondrial haplogroups. In summary, molecular diagnosis of mitochondrial disorders could be efficiently done from readily accessible samples, such as blood, with the use of a new sequencing platform. PMID- 22302391 TI - Hydroquinone-induced apoptosis of human lymphocytes through caspase 9/3 pathway. AB - Hydroquinone (HQ) is a major benzene metabolite, which is produced after benzene biotransformation. In this study, we investigated the toxic effect of HQ on lymphocytes. HQ significantly induced the apoptosis of lymphocytes isolated from normal peripheral blood in both dose and time dependent courses. Volatile organic compounds such as benzene, phenol, formaldehyde, o- and p-xylene, and toluene have no effect on lymphocyte apoptosis. HQ induced the cleavage of procaspase 3 and procaspase 9, indicating activation of the pro-apoptotic enzymes. Supernatant was collected from normal lymphocytes after HQ treatment and it significantly induced the apoptosis of normal lymphocytes as compared to supernatant collected from normal lymphocytes without HQ treatment. HQ reduced the secretion of MCP-1, IL-6 and IL-8 increased by in vitro incubation, although benzene and phenol are not effective in cytokine production. HQ increased the intracellular ROS production of lymphocytes. Benzene and phenol also increased the ROS production. In summary, HQ has a cytotoxic effect on lymphocytes by apoptosis induction and the pro-apoptotic signaling is involved in caspase 9/3 pathway. Our results demonstrated that HQ induces apoptosis by activating caspases 9/3 pathway and that the toxic effect seems to be dependent on lymphocyte metabolism. PMID- 22302392 TI - Genome-wide identification of palmitate-regulated immediate early genes and target genes in pancreatic beta-cells reveals a central role of NF-kappaB. AB - Free fatty acid-induced pancreatic beta-cell dysfunction plays a key role in the pathogenesis of type 2 diabetes. We conducted gene expression microarray analysis to comprehensively investigate the transcription machinery of palmitate-regulated genes in pancreatic beta-cells in vitro. In particular, mouse pancreatic betaTC3 cells were treated with palmitate in the presence or absence of cycloheximide (CHX), which blocks protein synthesis and thereby allows us to distinguish immediate early genes (IEGs) from their target genes. The microarray experiments identified 34 palmitate-regulated IEGs and 74 palmitate-regulated target genes. In silico promoter analysis revealed that transcription factor binding sites for NF-kappaB were over-represented, regulating approximately one-third of the palmitate-regulated target genes. In cells treated with CHX, nfkb1 showed an up regulation by palmitate, suggesting that NF-kappaB could be an IEG. Functional enrichment analysis of 27 palmitate-regulated genes with NF-kappaB binding sites showed an over-representation of genes involved in immune response, inflammatory response, defense response, taxis, regulation of cell proliferation, and regulation of cell death pathways. Electrophoretic mobility shift assay showed that palmitate stimulates NF-kappaB activity both in the presence and absence of CHX. In conclusion, by identifying IEGs and target genes, the present study depicted a comprehensive view of transcription machinery underlying palmitate induced inflammation and cell proliferation/death in pancreatic beta-cells and our data demonstrated the central role of NF-kappaB. PMID- 22302393 TI - Alpha-lipoic acid attenuates atherosclerotic lesions and inhibits proliferation of vascular smooth muscle cells through targeting of the Ras/MEK/ERK signaling pathway. AB - An infectious burden has been suggested to be associated with atherosclerosis in humans, based on the shared and underlying inflammatory responses during infection and atherosclerosis. However, the efficacy of anti-atherogenic drugs is yet to be tested against atherosclerosis in a scenario involving an infectious burden. We have examined alpha-lipoic acid (ALA) for anti-atherogenic effects in a hypercholesterolemic diet-induced atherosclerotic mouse model with inflammatory stimulation. C57BL/6 mice were fed with a hypercholesterolemic diet for 12 weeks to induce atherosclerosis. Lipopolysaccharide was intraperitoneally injected for the 1st week of study to simulate underlying infectious burden during development of atherosclerosis. ALA treatment alleviated atherosclerotic pathologies and reduced serum cholesterol and inflammatory cytokines. Consistently, atherosclerotic markers were improved by ALA treatment. In addition, ALA attenuated the proliferation and migration of vascular smooth muscle cells upon platelet-derived growth factor stimulation through the targeting of the Ras MEK1/2-ERK1/2 pathway. This study demonstrates the efficacy of ALA on atherosclerosis with immunological complication, by showing that ALA modulates multiple pathogenic aspects of atherosclerosis induced by a hypercholesterolemic diet with inflammatory stimulation consisting of hypercholesterolemia, inflammation and VSMC activation. PMID- 22302394 TI - Quercetin attenuates lindane induced oxidative stress in Wistar rats. AB - A wide number of pesticides, including highly persistent organochlorine compounds, such as lindane (gamma-Hexachlorocyclohexane), have deteriorative effect on fauna and flora by inducing oxidative stress. Lindane induces cell damage by producing free radicals and reactive oxygen species. Quercetin, a dietary flavonoid, is ubiquitous in fruits and vegetables and plays an important role in human health by virtue of its antioxidant function. In this study the flavonoid quercetin was used to investigate its antioxidative effect against lindane induced oxidative stress in rats. The level of lipid peroxidation, reduced glutathione (GSH) were analysed in addition to the antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione-s-transferase (GST) activities in the liver and kidney tissue. Levels of hepatic marker enzymes in serum like Aspartate transaminase (AST), Alanine transaminase (ALT), Alkaline phosphatase (ALP) and Lactate dehydrogenase (LDH) and renal markers like serum creatinine and serum urea were estimated. Administration of Lindane induced histopathological alterations and increased levels of serum hepatic and renal markers and malondialdehyde (MDA) with a significant decrease in GSH content and CAT, SOD, GPx and GST activities. Cotreatment of quercetin along with lindane significantly decreased the lindane induced alteration in histology, serum hepatic and renal markers and MDA and also improved the cellular antioxidant status. The results show that Quercetin ameliorates Lindane induced oxidative stress in liver and kidney. The quercetin exhibited chemopreventive effect when administered along with lindane. PMID- 22302395 TI - Influence of MIF, CD40, and CD226 polymorphisms on risk of rheumatoid arthritis. AB - Macrophage migration inhibitory factor (MIF) is a key pro-inflammatory mediator. It plays an important role part in the pathogenesis of several inflammatory and immune diseases. A functional single nucleotide polymorphism (SNP) of MIF -173 G/C is known to influence MIF promoter activity in T lymphoblast cell lines and is associated with a higher serum MIF level. The CD40 is also crucial for some relevant functions of the immune system and may be related to rheumatoid arthritis (RA). And CD226 is an important cell-surface receptor molecule involved in the adhesion and activation of T-cell. We hypothesized that these polymorphisms may contribute to RA susceptibility. We studied MIF -173 G/C, CD40, and CD226 gene polymorphisms in 214 patients with RA and 478 controls in a Chinese population. Genotyping was done by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). When the MIF -173 GG homozygote genotype was used as the reference group, the CC genotype was associated with a significantly increased risk for RA. In the recessive model, when the MIF -173 GG/GC genotypes were used as the reference group, the CC homozygote genotype was associated with a significant 1.56-fold increased susceptibility to RA. None of the CD40 rs1883832 C/T and CD226 rs763361 C/T polymorphisms achieved a significant difference in genotype distributions between cases and controls. In the stratification analyzes, a significantly increased risk for RA associated with the MIF -173 CC genotype was evident among CRP negative patients compared with the MIF -173 GG/GC genotype. For the CD40 rs1883832 C/T variant, the risk effects of CD40 rs1883832 TT versus CD40 rs1883832 CC/CT were significant in men. These findings suggested that the functional SNP MIF -173 G/C variant allele was associated with the development of RA. However, CD40 and CD226 gene polymorphisms may not be associated with RA susceptibility. Due to the limitation of sample size, this study should be considered preliminary. PMID- 22302396 TI - Identification of genes associated with tumor development in CaSki cells in the cosmic space. AB - It is important to understand the mechanisms of tumor development for curing cervical cancer. However, the molecular basis determining the different characteristics of tumor remains unclear. Space environment as a special study model can expand the study field of tumor development. To approach this, after human cervical carcinoma CaSki cells were flown on "Shen Zhou IV" space shuttle mission, the cell morphology and proliferation was investigated after flying to ground. We found that the growth of 48A9 CaSki cell (flight group) became slow compared with ground groups. Observation of cells by light microscopy revealed differences in cell morphology between ground controls and flight groups, and the flight group exhibited morphologic differences, characterized by rounder, smoother, decreased, smaller and low-adhension cells. Transmission electron microscope images showed the structure of the ultrastructural characteristics of 48A9 CaSki cells were clearly distinct from those of the ground CaSki cells in aspects of mitochondrion, cytoplasm, nucleus and ribosomes. MTT and soft agar assay showed that 48A9 CaSki cells grew slowly compared to ground control. Furthermore, suppression subtractive hybridization combining with reverse Northern blot was used to identify differently expression genes between flight and ground groups. These differentially expressed genes included cytoskeleton, cell differentiation, cell apoptosis, signal transduction, DNA repair, protein synthesis, substance metabolism, and antigen presentation. The identification of differently expressed genes which is likely to increase our understanding of the molecular processes underlying tumor development will provide new insight into tumor development mechanisms, and may facilitate the development of new anticancer strategies. PMID- 22302397 TI - ERCC1 expression as a prognostic and predictive factor in patients with non-small cell lung cancer: a meta-analysis. AB - It is hypothesized that high expression of the excision repair cross complementation group 1 (ERCC1) gene might be a positive prognostic factor, but predict decreased sensitivity to platinum-based chemotherapy. Results from the published data are inconsistent. To derive a more precise estimation of the relationship between ERCC1 and the prognosis and predictive response to chemotherapy of non-small cell lung cancer (NSCLC), a meta-analysis was performed. An electronic search of the PubMed and Embase database was performed. Hazard ratio (HR) for overall survival (OS) was pooled in early stage patients received surgery alone to analyze the prognosis of ERCC1 on NSCLC. HRs for OS in patients received surgery plus adjuvant chemotherapy and in patients received palliative chemotherapy and relative risk (RR) for overall response to chemotherapy were aggregated to analyze the prediction of ERCC1 on NSCLC. The pooled HR indicated that high ERCC1 levels were associated with longer survival in early stage patients received surgery alone (HR, 0.69; 95% confidence interval (CI), 0.58-0.83; P = 0.000). There was no difference in survival between high and low ERCC1 levels in patients received surgery plus adjuvant chemotherapy (HR, 1.41; 95% CI, 0.93-2.12; P = 0.106). However, high ERCC1 levels were associated with shorter survival and lower response to chemotherapy in advanced NSCLC patients received palliative chemotherapy (HR, 1.75; 95% CI, 1.39-2.22; P = 0.000; RR, 0.77; 95% CI, 0.64-0.93; P = 0.007; respectively). The meta-analysis indicated that high ERCC1 expression might be a favourable prognostic and a drug resistance predictive factor for NSCLC. PMID- 22302398 TI - Effects of ghrelin gene genotypes on the growth traits in Chinese cattle. AB - Ghrelin is an important peptide that stimulates food intake and regulates energy balance of animals. Single nucleotide polymorphisms of ghrelin gene in three Chinese cattle populations were investigated through PCR-SSCP and DNA sequencing. Five over-lapped DNA fragments were analyzed and a total of three ones exhibited different genotypes. Three genotypes and four SNPs (-415 A > G, -414 T > C, -321 C > A, and -172 A > G) were found on the -544 to +35 bp region (G-1) of ghrelin gene. On the locus of -1037 to -509 bp (G-2), two genotypes and one SNP (-726 A > T) were discovered. And in the exon1, exon2, and intron1 (G-4 locus, (+4 to +427)), two genotypes and one SNP were detected (+205 C > T, located in intron1). Positions of the five SNPs in the 5' regulatory region might be the transcription factor binding sites. The SNPs at -415 and -414 in the core binding sequence were found to cause the change of the site. Though the SNP at -172 did not change the binding site, it generated one new site at the same time. The frequencies of the genotypes varied differently in the three breeds. Results of ANOVA showed that G 1 was correlative to the ischium width (IW) of Nanyang cattle aged 18 months (p = 0.043). The least square analysis between genotypes at G-1 locus and growth traits in Nanyang cattle showed that the individuals (aged 18 months) with C genotype had greater IW than that of the other two genotypes. The C genotype might serve as one potential candidate genetic marker for cattle growth and development. PMID- 22302399 TI - DNA repair XRCC1 Arg399Gln polymorphism is associated with the risk of development of end-stage renal disease. AB - Patients with end-stage renal disease (ESRD) display enhanced genomic damage. DNA repair gene polymorphisms may affect DNA repair capacity and modulate susceptibility to ESRD. In this study, we aimed to determine the frequency of polymorphisms in two DNA repair enzyme genes, Xeroderma pigmentosum complementation group D (XPD) and X-ray cross-complementing group 1 (XRCC1), in patients with ESRD and to evaluate their association with ESRD development. By using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), we genotyped four single nucleotide polymorphisms (SNPs) in XPD codons 312 and 751 and XRCC1 codons 194 and 399 in 136 dialysis patients (71 patients undergoing hemodialysis and 65 subjected to peritoneal dialysis) and 147 healthy controls. Patients having XRCC1 399 Arg/Gln (OR:1.98; 95% CI: 1.21-3.25, P = 0.007) or XRCC1-399 Gln/Gln (OR: 3.95; 95% CI: 1.45-10.76, P = 0.005) genotype had a significantly higher risk of ESRD than those with XRCC1 399 Arg/Arg genotype. We also found a significantly higher frequency of the XRCC1 399Gln allele in patients with ESRD than in controls, with OR = 2.03 (95% CI = 1.08-3.81, P = 0.03). We further investigated the potential combined effect of these DNA repair variants on the risk of ESRD development. It was found that combination of the Arg/Gln or Gln/Gln genotypes of XRCC1 Arg399Gln polymorphism with the two possible genotypes of XPD-Asp312Asn or with the Lys/Gln or Gln/Gln genotypes of XPD Lys751Gln was significantly associated with the development of ESRD. This is the first report showing an association between DNA repair gene polymorphisms and ESRD development, and suggests that XRCC1 Arg399Gln polymorphism may confer increased risk for the development of the disease. Further larger studies should be conducted to confirm these results. PMID- 22302400 TI - The neurologic findings in Taybi-Linder syndrome (MOPD I/III): case report and review of the literature. AB - Taybi-Linder syndrome, also known as microcephalic osteodysplastic primordial dwarfism types I and III, is a rare disorder with presumed autosomal recessive inheritance. It is characterized by intrauterine growth retardation, distinctive bone dysplasia, and central nervous system malformations. We present two siblings with Taybi-Linder syndrome, with an emphasis on the neurological profile in this disease, which includes brain malformations, intractable epilepsy, sensory deficits, profound cognitive deficits, and neuroendocrine dysfunction. We also present distinctive correlative neuroimaging (MRI) and electroencephalographic (EEG) findings. Increased knowledge of the neurological profile of Taybi-Linder syndrome may be helpful for clinicians and genetic counselors managing these patients. PMID- 22302401 TI - Sandbar-regulated hydrodynamic influences on river hydrochemistry at Mengabang Telipot River, Peninsular Malaysia. AB - Influences of river hydrodynamic behaviours on hydrochemistry (salinity, pH, dissolved oxygen saturations and dissolved phosphorus) were evaluated through high spatial and temporal resolution study of a sandbar-regulated coastal river. River hydrodynamic during sandbar-closed event was characterized by minor dependency on tidal fluctuations, very gradual increase of water level and continual low flow velocity. These hydrodynamic behaviours established a hydrochemistry equilibrium, in which water properties generally were characterized by virtual absence of horizontal gradients while vertical stratifications were significant. In addition, the river was in high trophic status as algae blooms were visible. Conversely, river hydrodynamic in sandbar opened event was tidal-controlled and showed higher flow velocity. Horizontal gradients of water properties became significant while vertically more homogenised and with lower trophic status. In essence, this study reveals that estuarine sandbar directly regulates river hydrodynamic behaviours which in turn influences river hydrochemistry. PMID- 22302402 TI - Profile of child labor in Indian railways. AB - OBJECTIVES: To determine the socio-medical profile of child workers in Indian railways. METHODS: This was a prospective longitudinal survey over one year. The children up to the age of 14 y entering the reserved second class sleeper compartment of long distance trains in Indian railways were included. The data were collected regarding their profile by the investigators either by interviewing or observation as per situation in the moving train in a predesigned proforma. Data pertaining to the social, demographic and medical aspects were collected. RESULTS: A total of eighty one children were noted in 22500 kilometers of train journey. Sex distribution (8:1) was unequal with males outnumbering females. CONCLUSIONS: This study, first of its kind, attempted to delineate a distinctive socio-medical profile in a special group of children. It might, on the behalf of social pediatrics, increase the awareness and help the society to formulate a rehabilitation policy in collaboration with national and international organizations. PMID- 22302403 TI - Hypocalcemic tetany: an infrequently recognized association with acute dengue infection. PMID- 22302404 TI - A case control study on specific learning disorders in school going children in Bikaner city. AB - OBJECTIVE: To asses the prevalence of learning disorders in school going children and to compare the socio-demographic variables and other related factors with learning disorder. METHODS: All the 500 students of class III to V with all sections were given the dyslexia assessment questionnaire (DAQ) to fill; 468 students returned the completed forms.Statistical analysis was done using chi square test. Only 68 children scored >= 4 on DAQ were given MISIC (Mallin's intelligence scale for Indian children) for IQ assessment and DST-J for dyslexia screening. Forty-eight students were labeled as dyslexia and further diagnosis was confirmed by DSM IV- TR classification. RESULTS: Prevalence of learning disorders (LD) was found to be 10.25% with higher in males than females (11.40% vs. 7.14%).The delivery complications (20.83% vs. 4.17%; X 2-4.667, p value 0.031) were more in LD and more family members were left handed (16.67% vs. 2.08%; X 2-4.41, p value-0.036) as compared to control group. In classroom behavior, children with LD asked questions less (10.42% vs. 75%; X 2-40.91, p value-0.0001), answered questions less frequently (6.25% vs. 79.16%; X 2-52.15, p value-0.0001) and took notes less attentively than control group (4.17% vs. 58.33%; X 2-32.77, p value-0.0001). CONCLUSIONS: The current study, therefore, is an attempt to identify children with learning disorders and explore the prevalence of the problem and etiological factors e.g., family environment, social factors and developmental issues of child and associated co-morbidities. More studies with larger sample size should be undertaken to get accurate picture of these disorders.There is also need for some community based programme to raise the level of awareness and knowledge about these disorders in general population. PMID- 22302405 TI - A novel and simple method of production and biophysical characterization of a mini-membrane protein, Ost4p: a subunit of yeast oligosaccharyl transferase. AB - Asparagine-linked glycosylation is an essential and highly conserved protein modification reaction. In eukaryotes, oligosaccharyl transferase (OT), a multi subunit membrane-associated enzyme complex, catalyzes this reaction in newly synthesized proteins. In Saccharomyces cerevisiae, OT consists of nine nonidentical membrane proteins. Ost4p, the smallest subunit, bridges the catalytic subunit Stt3p with Ost3p. Mutation of transmembrane residues 18-24 in Ost4p has negative effect on OT activity, disrupts the Stt3p-Ost4p-Ost3p complex, results in temperature-sensitive phenotype, and hypoglycosylation. Heterologous expression and purification of integral membrane proteins are the bottleneck in membrane protein research. The authors report the cloning, successful overexpression and purification of recombinant Ost4p with a novel but simple method producing milligram quantities of pure protein. GB1 protein was found to be the most suitable tag for the large scale production of Ost4p. The cleavage of Ost4p conveniently leaves GB1 protein in solution eliminating further purification. The precipitated pure Ost4p is reconstituted in appropriate membrane mimetic. The recombinant protein is highly helical as indicated by the far-UV CD spectrum. The well-dispersed heteronuclear single quantum coherence spectrum indicates that this minimembrane protein is well-folded. The successful production of pure recombinant Ost4p with a novel yet simple method may have important ramification for the production of other membrane proteins. PMID- 22302406 TI - Pharmacokinetics and tissue and tumor exposure of CP-31398, a p53-stabilizing agent, in rats. AB - PURPOSE: CP-31398 (N0-[2-[(E)-2-(4-methoxyphenyl)ethenyl] quinazolin-4-yl]-N,N dimethylpropane-1,3-diamine hydrochloride) is one of the new class of agents that can stabilize the DNA-binding domain of p53 and thereby maintain the activity of p53 as a tumor suppressor and transcription factor. Through its activity as a p53 stabilizer, CP-31398 demonstrates significant cancer preventive and therapeutic activity in several in vivo animal models. The objective of the current study was to describe the pharmacokinetic profile and tissue distribution of this novel agent following intravenous or oral (gavage and dietary) administration. METHODS: CP-31398 was administered to male CD and F344 rats as a single intravenous bolus dose or by daily oral gavage dosing. Male F344 rats also received drug as an ad libitum dietary supplement. Plasma, liver, skin, colon, and colon tumor samples were collected after oral dosing. Concentrations of CP-31398 in plasma and tissue samples were analyzed using LC-MS/MS, and the resultant data were subjected to a non-compartmental pharmacokinetic analysis. RESULTS: Bioavailability (12-32%), elimination half-life (14-20 h), clearance (4.2-4.8 l/h/kg), and volume of distribution (70-82 l/kg) were determined. Tissue levels of CP-31398 after oral (gavage or diet) administration were several orders of magnitude higher than were corresponding plasma concentrations; CP-31398 levels were especially high in colon and liver. Levels of CP-31398 in tissues were higher after gavage dosing than after dietary administration. CONCLUSIONS: CP-31398 is bioavailable and has a relatively long elimination half-life, which supports the achievement of plasma steady-state levels with a once daily dosing regimen. CP-31398 exhibits a dramatically high volume of distribution, which is consistent with its tissue concentrations being much higher than corresponding plasma levels. It is accumulated in colon tumor tissues, albeit at lower concentrations than found in liver, skin, and colon. PMID- 22302407 TI - Optimization of patient selection for EGFR-TKIs in advanced non-small cell lung cancer by combined analysis of KRAS, PIK3CA, MET, and non-sensitizing EGFR mutations. AB - BACKGROUND: We present a comprehensive analysis of KRAS, PIK3CA, MET, and non sensitizing EGFR mutations in advanced non-small cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitors (TKIs), with the aim of clarifying the relative contribution of these molecular alterations to resistance. PATIENTS AND METHODS: One hundred and sixty-six patients with advanced NSCLC treated with EGFR-TKIs with available archival tissue specimens were included. EGFR (exons 18-21), KRAS (exons 2, 3), PIK3CA (exons 9, 20), and MET (exons 14, 15) mutations were analyzed using PCR-based sequencing. Among all the mutations evaluated, only KRAS, PIK3CA, MET, and non-sensitizing EGFR mutations, defined as "TKI non-sensitizing mutations" were used for response, time to progression (TTP), and overall survival (OS) analysis. RESULTS: TKI non sensitizing mutations were associated with disease progression (p = 0.001), shorter TTP (p < 0.0001), and worse OS (p = 0.03). Cox's multivariate analysis including histology and performance status showed that TKI non-sensitizing mutations were independent factors for shorter TTP (p < 0.0001) and worse OS (p = 0.01). CONCLUSIONS: When KRAS, PIK3CA, MET, and non-sensitizing EGFR mutations are concomitant, up to 96.0% of NSCLC patients unlikely to respond to TKIs can be identified, and they represented independent negative prognostic factors. Comprehensive molecular dissection of EGFR signaling pathways should be considered to select advanced NSCLC patients for TKIs therapies. PMID- 22302408 TI - RRM1 and ERCC1 expression in peripheral blood versus tumor tissue in gemcitabine/carboplatin-treated advanced non-small cell lung cancer. AB - PURPOSE: To comparatively evaluate the prognostic or predictive value of ribonucleotide reductase M1 (RRM1) and excision repair cross-complementation 1 (ERCC1) gene expression in peripheral blood versus tumor tissue from patients with advanced non-small cell lung cancer (NSCLC) treated by gemcitabine/platinum chemotherapy. METHODS: A total of 49 patients with advanced NSCLC receiving gemcitabine plus carboplatin chemotherapy were studied. RRM1 and ERCC1 mRNA levels in the peripheral blood and tumor tissue were determined by real-time fluorescent quantitative PCR. The relationships between gene expression and clinical and pathological factors, response to chemotherapy as well as prognosis, were evaluated. RESULTS: RRM1 expression in peripheral blood and tumor tissue, but not ERCC1 expression, was found to be positively correlated (r = 0.332, 0.258; P = 0.020, 0.073; respectively). RRM1 and ERCC1 expression levels were nearly synchronous in both peripheral blood (r = 0.351; P = 0.013) and tumor tissue (r = 0.634; P < 0.001). Neither was correlated with clinical and pathological factors. PATIENTS: with low RRM1 expression in peripheral blood or low RRM1 or ERCC1 expression in tumor tissue experienced better response to chemotherapy (50.0 vs. 16.0%, 50.0 vs. 16.0%, and 54.2 vs. 12.0%; P = 0.012, 0.012, and 0.003; respectively), longer median survival (18.5 vs. 13.0 months, 18.5 vs. 12.0 months, and 19.8 vs. 12.5 months; P = 0.043, 0.014 and 0.007; respectively), and longer progression-free survival (6.0 vs. 4.0 months, 7.8 vs. 3.9 months, and 5.8 vs. 3.8 months; P = 0.044, 0.016, and 0.008; respectively). Cox multivariate regression analysis showed that ERCC1 expression in tumor tissue was independent indicator for overall survival. CONCLUSIONS: Advanced NSCLC patients with low RRM1 mRNA expression both in peripheral blood and in tumor tissue could benefit from gemcitabine/carboplatin chemotherapy. ERCC1 mRNA expression in tumor tissue may be a predictive and prognostic indicator in advanced NSCLC patients receiving gemcitabine/carboplatin chemotherapy. PMID- 22302409 TI - Predicting platinum resistance in primary advanced ovarian cancer patients with an in vitro resistance index. AB - PURPOSE: We aimed to identify primary platinum resistance in epithelial ovarian cancer (OC) patients with FIGO stage III-IV disease by an in vitro drug-response assay and to correlate the findings with clinical response. We considered whether neoadjuvant chemotherapy or anatomic sample site and tumor heterogeneity would influence the results. METHODS: We combined the ATP-based tumor-chemosensitivity and the extreme drug resistance assays for testing of 85 biopsies from 58 patients. Tumors were classified as sensitive or resistant by a resistance index (RI). We did separate analyses of primary tumors and metastases and compared chemo-naive samples with samples obtained after neoadjuvant chemotherapy. Results were analyzed for association with clinical platinum resistance, progression-free survival (PFS), and overall survival (OS). RESULTS: RI . 250 predicted primary platinum resistance, without misclassification of sensitive patients. The test sensitivity for primary tumors was 15/15, specificity 3/10, negative predictive value 3/3, and positive predictive value 15/22. Patients with in vitro platinum resistant samples had shorter PFS compared with patients with sensitive samples (3.4 vs. 10.0 months, p = 0.02). Comparing patient-matched primary and metastatic samples, there was about 1/3 mismatch in resistance. RI for platinum was lower in primary tumors exposed to neoadjuvant chemotherapy than in chemo-naive tumors (p < 0.01). CONCLUSIONS: This in vitro assay predicted primary platinum resistance, without misclassification of sensitive OC patients, and the results were significantly associated with PFS. We suggest that samples from primary tumor and metastatic samples have different responses to chemotherapy and that exposure to chemotherapy might induce in vitro platinum resistance. PMID- 22302410 TI - Multilevel latent variable models for global health-related quality of life assessment. AB - Quality of life (QOL) assessment is a key component of many clinical studies and frequently requires the use of single global summary measures that capture the overall balance of findings from a potentially wide-ranging assessment of QOL issues. We propose and evaluate an irregular multilevel latent variable model suitable for use as a global summary tool for health-related QOL assessments. The proposed model is a multiple indicator and multiple cause style of model with a two-level latent variable structure. We approach the modeling from a general multilevel modeling perspective, using a combination of random and nonrandom cluster types to accommodate the mixture of issues commonly evaluated in health related QOL assessments--overall perceptions of QOL and health, along with specific psychological, physical, social, and functional issues. Using clinical trial data, we evaluate the merits and application of this approach in detail, both for mean global QOL and for change from baseline. We show that the proposed model generally performs well in comparing global patterns of treatment effect and provides more precise and reliable estimates than several common alternatives such as selecting from or averaging observed global item measures. A variety of computational methods could be used for estimation. We derived a closed-form expression for the marginal likelihood that can be used to obtain maximum likelihood parameter estimates when normality assumptions are reasonable. Our approach is useful for QOL evaluations aimed at pharmacoeconomic or individual clinical decision making and in obtaining summary QOL measures for use in quality adjusted survival analyses. PMID- 22302411 TI - How does visuomotor priming differ for biological and non-biological stimuli? A review of the evidence. AB - Visuomotor priming occurs when our actions are influenced by observing a compatible or incompatible action. Here we ask whether visuomotor priming is specific to human, biological actions or generalises to non-biological movements, such as abstract shapes or robots. Reviewing the evidence indicates that priming occurs for both types of stimuli and emphasises the contributions of both bottom up (e.g. stimulus saliency, appearance, kinematics) and top-down (e.g. attention and prior knowledge) factors. We propose a model suggesting that although bottom up features play a critical role, the degree of difference in priming for biological versus non-biological stimuli can be ultimately shaped by top-down factors. PMID- 22302412 TI - Chemometrics applications in biotech processes: assessing process comparability. AB - A typical biotech process starts with the vial of the cell bank, ends with the final product and has anywhere from 15 to 30 unit operations in series. The total number of process variables (input and output parameters) and other variables (raw materials) can add up to several hundred variables. As the manufacturing process is widely accepted to have significant impact on the quality of the product, the regulatory agencies require an assessment of process comparability across different phases of manufacturing (Phase I vs. Phase II vs. Phase III vs. Commercial) as well as other key activities during product commercialization (process scale-up, technology transfer, and process improvement). However, assessing comparability for a process with such a large number of variables is nontrivial and often companies resort to qualitative comparisons. In this article, we present a quantitative approach for assessing process comparability via use of chemometrics. To our knowledge this is the first time that such an approach has been published for biotech processing. The approach has been applied to an industrial case study involving evaluation of two processes that are being used for commercial manufacturing of a major biosimilar product. It has been demonstrated that the proposed approach is able to successfully identify the unit operations in the two processes that are operating differently. We expect this approach, which can also be applied toward assessing product comparability, to be of great use to both the regulators and the industry which otherwise struggle to assess comparability. PMID- 22302413 TI - Emerging drugs of abuse: what was new yesterday is new today. PMID- 22302414 TI - Learning through inter- and intradisciplinary problem solving: using cognitive apprenticeship to analyse doctor-to-doctor consultation. AB - Today's healthcare can be characterised by the increasing importance of specialisation that requires cooperation across disciplines and specialities. In view of the number of educational programmes for interdisciplinary cooperation, surprisingly little is known on how learning arises from interdisciplinary work. In order to analyse the learning and teaching practices of interdisciplinary cooperation, a multiple case study research focused on how consults, i.e., doctor to-doctor consultations between medical doctors from different disciplines were carried out: semi-structured interviews with doctors of all levels of seniority from two hospital sites in Switzerland were conducted. Starting with a priori constructs based on the 'methods' underpinning cognitive apprenticeship (CA), the transcribed interviews were analysed according to the principles of qualitative content analysis. The research contributes to three debates: (1) socio-cognitive and situated learning, (2) intra- and interdisciplinary learning in clinical settings, and (3), more generally, to cooperation and problem solving. Patient cases, which necessitate the cooperation of doctors in consults across boundaries of clinical specialisms, trigger intra- as well as interdisciplinary learning and offer numerous and varied opportunities for learning by requesting doctors as well as for on-call doctors, in particular those in residence. The relevance of consults for learning can also be verified from the perspective of CA which is commonly used by experts, albeit in varying forms, degrees of frequency and quality, and valued by learners. Through data analysis a model for collaborative problem-solving and help-seeking was developed which shows the interplay of pedagogical 'methods' of CA in informal clinical learning contexts. PMID- 22302415 TI - Nanowire piezo-phototronic photodetector: theory and experimental design. AB - The piezo-phototronic effect is about the use of the inner crystal piezoelectric potential to tune/control charge carrier generation, separation, transport and/or recombination in optoelectronic devices. In this paper, a theoretical model for describing the characteristics of a metal-nanowire-metal structured piezo phototronic photodetector is constructed. Numerical simulations fit well to the experimental results of a CdS and ZnO nanowire based visible and UV detector, respectively. PMID- 22302416 TI - Stress-free state of the red blood cell membrane and the deformation of its skeleton. AB - The response of a red blood cell (RBC) to deformation depends on its membrane, a composite of a lipid bilayer and a skeleton, which is a closed, two-dimensional network of spectrin tetramers as its bonds. The deformation of the skeleton and its lateral redistribution are studied in terms of the RBC resting state for a fixed geometry of the RBC, partially aspirated into a micropipette. The geometry of the RBC skeleton in its initial state is taken to be either two concentric circles, a references biconcave shape or a sphere. It is assumed that in its initial state the skeleton is distributed laterally in a homogeneous manner with its bonds either unstressed, presenting its stress-free state, or prestressed. The lateral distribution was calculated using a variational calculation. It was assumed that the spectrin tetramer bonds exhibit a linear elasticity. The results showed a significant effect of the initial skeleton geometry on its lateral distribution in the deformed state. The proposed model is used to analyze the measurements of skeleton extension ratios by the method of applying two modes of RBC micropipette aspiration. PMID- 22302417 TI - Abatacept in subjects who switch from intravenous to subcutaneous therapy: results from the phase IIIb ATTUNE study. AB - OBJECTIVE: To assess safety, immunogenicity and efficacy in rheumatoid arthritis (RA) patients switched from long-term intravenous to subcutaneous (SC) abatacept. METHODS: In this phase IIIb, open-label, single-arm trial, patients who completed >=4 years of intravenous abatacept (in long-term extensions of two phase III studies) were enrolled to receive SC abatacept (125 mg/week). The primary objective was safety during the first 3 months after switching from intravenous therapy. RESULTS: 123 patients entered the study (mean Disease Activity Score 28 (based on C reactive protein) and HAQ-DI of 3.4 and 0.94, respectively). At month 3, 120 (97.6%) patients were continuing to receive SC abatacept; no patients discontinued due to lack of efficacy. Adverse events (AEs) were reported in 49 (39.8%) patients through month 3. One patient (0.8%) discontinued due to an AE and one patient (0.8%) experienced a serious AE. Two (1.6%) patients had SC injection site reactions (erythema, pain), both with mild intensity. Clinical efficacy was maintained throughout. Limited impact on immunogenicity was observed when switching routes of administration. CONCLUSION: These data demonstrate that patients can switch from long-term monthly intravenous abatacept to a weekly fixed dose of 125 mg SC abatacept with no increased safety concerns. This study further supports SC abatacept as an alternative treatment option for patients with RA. PMID- 22302418 TI - Setting pay for performance targets: do poor performers give up? AB - We examine the effect of a health plan's pay for performance incentives on the percentage of outpatient drug prescriptions that are filled with generic rather than brand-name drugs in physicians' practices in an established physician network - the generic prescription rate (GPR). The financial reward was based on the performance of the entire network, but the network implemented rewards at the practice level. Practice-level rewards were awarded on an all-or-nothing basis if the GPR met or exceeded specialty-specific targets that increased each year. Although that design gave the practices a strong incentive to meet the target, practices performing far below the target might 'give up', costing the network its reward. Using a partial adjustment model, we estimate that in the absence of pay for performance, the average equilibrium value of GPR was 58.3%. We estimate that GPR would be maximized if the target were set at 77%. The GPR-maximizing target would induce an improvement in average GPR from 58.3% to 65.8% or 7.5 percentage points. When the target is set above 80%, practices with equilibrium GPR below 58.3% will 'give up' in the sense that they will not improve relative to their equilibrium value. PMID- 22302419 TI - On the covariance of two correlated log-odds ratios. AB - In many applications two correlated estimates of an effect size need to be considered simultaneously to be combined or compared. Apparently, there is a need for calculating their covariance, which however requires access to the individual data that may not be available to a researcher performing the analysis. We present a simple and efficient method for calculating the covariance of two correlated log-odds ratios. The method is very simple, is based on the well-known large sample approximations, can be applied using only data that are available in the published reports and more importantly, is very general, because it is shown to encompass several previously derived estimates (multiple outcomes, multiple treatments, dose-response models, mutually exclusive outcomes, genetic association studies) as special cases. By encompassing the previous approaches in a unified framework, the method allows easily deriving estimates for the covariance concerning problems that were not easy to be obtained otherwise. We show that the method can be used to derive the covariance of log-odds ratios from matched and unmatched case-control studies that use the same cases, a situation that has been addressed in the past only using individual data. Future applications of the method are discussed. PMID- 22302420 TI - Simulation optimization of PSA-threshold based prostate cancer screening policies. AB - We describe a simulation optimization method to design PSA screening policies based on expected quality adjusted life years (QALYs). Our method integrates a simulation model in a genetic algorithm which uses a probabilistic method for selection of the best policy. We present computational results about the efficiency of our algorithm. The best policy generated by our algorithm is compared to previously recommended screening policies. Using the policies determined by our model, we present evidence that patients should be screened more aggressively but for a shorter length of time than previously published guidelines recommended. PMID- 22302421 TI - Quantitative structure-activity relationships of antimicrobial fatty acids and derivatives against Staphylococcus aureus. AB - Fatty acids and derivatives (FADs) are resources for natural antimicrobials. In order to screen for additional potent antimicrobial agents, the antimicrobial activities of FADs against Staphylococcus aureus were examined using a microplate assay. Monoglycerides of fatty acids were the most potent class of fatty acids, among which monotridecanoin possessed the most potent antimicrobial activity. The conventional quantitative structure-activity relationship (QSAR) and comparative molecular field analysis (CoMFA) were performed to establish two statistically reliable models (conventional QSAR: R(2)=0.942, Q(2)(LOO)=0.910; CoMFA: R(2)=0.979, Q(2)=0.588, respectively). Improved forecasting can be achieved by the combination of these two models that provide a good insight into the structure-activity relationships of the FADs and that may be useful to design new FADs as antimicrobial agents. PMID- 22302422 TI - Survey of antioxidant capacity and phenolic composition of blueberry, blackberry, and strawberry in Nanjing. AB - Berries are a good source of natural antioxidants. In the present study, the total antioxidant capacity and phenolic composition of three berry fruits (blueberry, blackberry, and strawberry) cultivated in Nanjing were investigated. Blueberry, with a Trolox equivalent antioxidant capacity (TEAC) value of 14.98 mmol Trolox/100 g dry weight (DW), exhibited the strongest total antioxidant capacity using both the 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods. Blueberry also had the highest total phenolic content (TPC, 9.44 mg gallic acid/g DW), total flavonoid content (TFC, 36.08 mg rutin/g DW), and total anthocyanidin content (TAC, 24.38 mg catechin/g DW). A preliminary analysis using high performance liquid chromatography (HPLC) showed that the blueberry, blackberry, and strawberry samples tested contained a range of phenolic acids (including gallic acid, protocatechuic acid, p-hydroxybenzoic acid, vanillic acid, caffeic acid, p-coumaric acid, ferulic acid, ellagic acid, and cinnamic acid) and various types of flavonoids (flavone: luteolin; flavonols: rutin, myricetin, quercetrin, and quercetin; flavanols: gallocatechin, epigallocatechin, catechin, and catechin gallate; anthocyanidins: malvidin-3-galactoside, malvidin-3-glucoside, and cyanidin). In particular, the blueberries had high levels of proanthocyanidins and anthocyanidins, which might be responsible for their strong antioxidant activities. These results indicate a potential market role for berries (especially blueberries) as a functional food ingredient or nutraceutical. PMID- 22302423 TI - Optimization of succinic acid fermentation with Actinobacillus succinogenes by response surface methodology (RSM). AB - Succinic acid is considered as an important platform chemical. Succinic acid fermentation with Actinobacillus succinogenes strain BE-1 was optimized by central composite design (CCD) using a response surface methodology (RSM). The optimized production of succinic acid was predicted and the interactive effects between glucose, yeast extract, and magnesium carbonate were investigated. As a result, a model for predicting the concentration of succinic acid production was developed. The accuracy of the model was confirmed by the analysis of variance (ANOVA), and the validity was further proved by verification experiments showing that percentage errors between actual and predicted values varied from 3.02% to 6.38%. In addition, it was observed that the interactive effect between yeast extract and magnesium carbonate was statistically significant. In conclusion, RSM is an effective and useful method for optimizing the medium components and investigating the interactive effects, and can provide valuable information for succinic acid scale-up fermentation using A. succinogenes strain BE-1. PMID- 22302424 TI - Immobilization of foreign protein into polyhedra of Bombyx mori nucleopolyhedrovirus (BmNPV). AB - In the late phase of Bombyx mori nucleopolyhedrovirus (BmNPV) infection, a large amount of polyhedra appear in the infected cell nucleolus, these polyhedra being dense protein crystals protecting the incorporated virions from the harsh environment. To investigate whether the foreign protein could be immobilized into the polyhedra of BmNPV, two recombinant baculoviruses were generated by a novel BmNPV polyhedrin-plus (polh(+)) Bac-to-Bac system, designated as vBmBac(polh(+)) enhanced green fluorescent protein (EGFP) and vBmBac(polh(+))-LacZ, which can express the polyhedrin and foreign protein simultaneously. Light microscopy analysis showed that all viruses produced polyhedra of normal appearance. Green fluorescence can be apparently detected on the surface of the vBmBac(polh(+)) EGFP polyhedra, but not the BmNPV polyhedra. Fluorescence analysis and anti desiccation testing confirmed that EGFP was embedded in the polyhedra. As expected, the vBmBac(polh(+))-LacZ polyhedra contained an amount of LacZ and had a higher beta-galactosidase activity. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting were also performed to verify if the foreign proteins were immobilized into polyhedra. This study provides a new inspiration for efficient preservation of useful proteins and development of new pesticides with toxic proteins. PMID- 22302425 TI - Development of an electrochemical immunoassay for detection of gatifloxacin in swine urine. AB - To detect gatifloxacin (GAT) residue in swine urine, an electrochemical immunoassay was established. An indirect competitive immunoassay was developed, in which the coating antigen is immobilized in an enzyme-linked immunosorbent assay (ELISA) plate and GAT residue from the sample competes with the limited binding sites in added anti-GAT antibody. Horseradish peroxidase (HRP) conjugated to goat anti-rabbit IgG was used as the enzymatic label. A carbon fiber working electrode was constructed and current signals were detected by using hydrogen peroxide as a substrate and hydroquinone as an electrochemical mediator. The electrochemical immunoassay was evaluated by analysis of GAT in buffer or swine urine and an average value of half inhibition concentration (IC(50)) of 8.9 ng/ml was obtained. Excellent specificity of the antibody was achieved with little cross-reaction with lomefloxacin (3.0%), ciprofloxacin (3.0%), and ofloxacin (1.9%) among commonly used (fluoro)quinolones. In conclusion, the immunoassay system developed in this research can be used as a rapid, powerful and on-site analytical tool to detect GAT residue in foods and food products. PMID- 22302426 TI - Alternaria toxin-induced resistance against rose aphids and olfactory response of aphids to toxin-induced volatiles of rose plants. AB - The search for active toxins for managing weeds or plant diseases is believed to be a promising avenue of investigation. However, the effects of Alternaria toxins on insects have just begun to be investigated. Bioactivities of toxins from four strains of Alternaria alternata on Rosa chinensis and rose aphid Macrosiphum rosivorum were tested in the present study. At a concentration of 50.0 MUg/ml, the crude extract (toxin) of strain 7484 was found not to be harmful to rose plants with excised leaf-puncture method (P>=0.079), and rose plants showed enhanced resistance to rose aphids when this Alternaria toxin was sprayed on the plants (P<=0.001). However, this toxin caused no detrimental effects on aphids in insecticidal bioassay at a concentration of 10.0 to 160.0 MUg/ml (P>=0.096). Therefore, the Alternaria toxin had significantly induced the resistance of rose plants against rose aphids, demonstrating that the resistance mechanism triggered by the Alternaria toxin in the rose plant may also be used by the plant to defend itself against insects. Further bioassays aimed to discover the olfactory responses of aphids to the toxin-induced volatiles of host plants. The aphids were significantly more attracted to both volatiles emitted and collected from control rose plants than to both volatiles emitted and collected from the toxin treated rose plants (P<=0.014). This result showed that the toxin-induced resistance related to the volatile changes of host plants. PMID- 22302427 TI - Chlorocholine chloride and paclobutrazol treatments promote carbohydrate accumulation in bulbs of Lilium Oriental hybrids 'Sorbonne'. AB - The present study was to test the hypothesis that the plant growth retardants chlorocholine chloride (CCC) and paclobutrazol (PBZ) could improve the carbohydrate accumulation in lily bulbs by enhancing photosynthetic capacity and changing endogenous hormones. Plants of Lilium Oriental hybrids 'Sorbonne' were treated with a foliar spray of CCC or PBZ (both at 300 mg/L) solution, at six weeks after planting (6 WAP). The morphological parameters, endogenous hormone contents (gibberellic acid (GA), abscisic acid (ABA), and indole-3-acetic acid (IAA)), and carbohydrate contents were measured from 6 to 18 WAP, at 2-week intervals. The results showed that CCC increased the biomass of leaves and stems which might produce more photoassimilates available for transportation and utilization. However, PBZ treatment suppressed vegetative growth and favored photoassimilate transportation into bulbs. A slight delay of bud and anthesis formation was observed in both treated plants. CCC and PBZ treatments substantially enhanced the sucrose contents in leaves probably due to the increase of chlorophyll contents. Treatment with CCC or PBZ decreased GA but increased IAA contents in lily bulbs which might stimulate starch accumulation and formation of new scales. Our experiment suggested that CCC or PBZ treatment is an effective method to promote carbohydrate accumulation in lily bulbs. PMID- 22302428 TI - Neural network and principal component regression in non-destructive soluble solids content assessment: a comparison. AB - Visible and near infrared spectroscopy is a non-destructive, green, and rapid technology that can be utilized to estimate the components of interest without conditioning it, as compared with classical analytical methods. The objective of this paper is to compare the performance of artificial neural network (ANN) (a nonlinear model) and principal component regression (PCR) (a linear model) based on visible and shortwave near infrared (VIS-SWNIR) (400-1000 nm) spectra in the non-destructive soluble solids content measurement of an apple. First, we used multiplicative scattering correction to pre-process the spectral data. Second, PCR was applied to estimate the optimal number of input variables. Third, the input variables with an optimal amount were used as the inputs of both multiple linear regression and ANN models. The initial weights and the number of hidden neurons were adjusted to optimize the performance of ANN. Findings suggest that the predictive performance of ANN with two hidden neurons outperforms that of PCR. PMID- 22302429 TI - Protein sequence analysis based on hydropathy profile of amino acids. AB - Biology sequence comparison is a fundamental task in computational biology. According to the hydropathy profile of amino acids, a protein sequence is taken as a string with three letters. Three curves of the new protein sequence were defined to describe the protein sequence. A new method to analyze the similarity/dissimilarity of protein sequence was proposed based on the conditional probability of the protein sequence. Finally, the protein sequences of ND6 (NADH dehydrogenase subunit 6) protein of eight species were taken as an example to illustrate the new approach. The results demonstrated that the method is convenient and efficient. PMID- 22302430 TI - Familial 4.8 MB deletion on 18q23 associated with growth hormone insufficiency and phenotypic variability. AB - The deletion of the long arm of chromosome 18 causes a contiguous gene deletion syndrome with a highly variable phenotype, usually related to the extent of the deleted region. The most commonly reported clinical features include: decreased growth, microcephaly, facial abnormalities, hypotonia, developmental delay, intellectual disability, congenital aural atresia with hearing impairment and limb anomalies. Here we report on a familial terminal deletion of 18q23 region transmitted from a mother to two daughters, resulting in a remarkable phenotypic variability. The deletion was first detected by conventional cytogenetic analysis in one daughter and subsequently characterized using fluorescence in situ hybridization (FISH) and array-CGH. FISH analysis using subtelomeric 18p and 18q probes confirmed the 18qter deletion in the three patients, and FISH with a whole chromosome painting probe specific for chromosome 18 excluded rearrangements with other chromosomes. Array-CGH analysis allowed us to precisely define the extent of the deletion, which spans 4.8 Mb from 71,236,891 to 76,093,303 genomic positions and includes GALR1 and MBP genes, among others. High-resolution analysis of the deletion, besides a detailed clinical assessment, has provided important data for phenotype-genotype correlation and genetic counseling in this family. Furthermore, this study adds valuable information for phenotype-genotype correlation in 18q- syndrome and might facilitate future search for candidate genes involved in each phenotypic trait. PMID- 22302431 TI - Comparison of quality of life between Native and non-Native cancer survivors: Native and non-Native cancer survivors' QOL. AB - This paper compares quality of life (QOL) outcomes between Native American and non-Native cancer survivors. Native Patient Navigators helped Native cancer patients complete a 114-item QOL survey and access survivorship information available on the NACES website. The survey was modified from Ferrell et. al's QOL measure and assessed the four domains of cancer survivorship: physical, psychological, social, and spiritual. Findings from Native survivors were compared to Ferrell's findings. This is the first time that QOL outcomes have been compared between Native and Non-Native cancer survivors. Natives scored lower for physical and social QOL, the same for psychological QOL, and higher for spiritual QOL in comparison to non-Natives. Overall QOL scores were the same. Although this is the largest sample of Native cancer survivors reported in peer reviewed manuscripts, these Native survivorship data are based on a self-selected group and it is unknown if the findings are generalizable to others. PMID- 22302432 TI - Prefrontal cortex cytoarchitecture in normal aging and Alzheimer's disease: a relationship with IQ. AB - We have previously shown that the minicolumnar spacing of neurons in the cerebral cortex relates to cognitive ability, and that minicolumn thinning occurs in old age. The present study examines further the relationship between cognitive ability and cortical fine structure(minicolumn organization and neuropathology) in the dorsolateral prefrontal cortex (dlPFC) and the parahippocampal gyrus (PHG) in mild cognitive impairment (MCI)and Alzheimer's disease (AD). Premortem neuropsychological scores were related to postmortem microanatomy in 58 adults (20 normal controls, 18 MCI, and 20 confirmed AD patients). We found a correspondence between minicolumn thinning in the dlPFC and IQ decline in dementia.In mild impairment, IQ remained stable, as did dlPFC minicolumn width and dlPFC plaque load. IQ only declined as dlPFC minicolumn thinning occurred and dlPFC plaque load increased in more severe dementia. By contrast, plaque load increased and minicolumns became steadily thinner in the PHG, where minicolumn width correlated with declining mini-mental state examination score across both MCI and severe dementia. By including a further 14 younger control subjects, we found that in normal healthy aging, minicolumn width decreased in the dlPFC, whereas PHG minicolumn width did not change.AD patients in our dataset with higher IQ were older at time of death and had less pathology, which supports a neural basis for the cognitive reserve hypothesis. PMID- 22302433 TI - A VBM study demonstrating 'apparent' effects of a single dose of medication on T1-weighted MRIs. AB - Voxel-based morphometry (VBM) studies have interpreted longitudinal medication- or behaviorally induced changes observed on T1-weighted magnetic resonance images (MRIs) as changes in neuronal structure. Although neurogenesis or atrophy certainly occurs, the use of T1-weighted scans to identify change in brain structure in vivo in humans has vulnerability: the T1 relaxation time for arterial blood and gray matter are not clearly distinguishable and therefore, apparent reported structural findings might be at least partially related to changes in blood flow or other physiological signals. To examine the hypothesis that apparent structural modifications may reflect changes introduced by additional mechanisms irrespective of potential neuronal growth/atrophy, we acquired a high-resolution T1-weighted structural scan and a 5-min perfusion fMRI scan (a measurement of blood flow), before and after administration of an acute pharmacological manipulation. In a within-subject design, 15 subjects were either un-medicated or were administered a 20 mg dose of baclofen (an FDA-approved anti spastic) approximately 110 min before acquiring a T1-weighted scan and a pseudo continuous arterial spin labeled perfusion fMRI scan. Using diffeomorphic anatomical registration through exponentiated lie algebra within SPM7, we observed macroscopic, and therefore implausible, baclofen-induced decreases in VBM 'gray matter' signal in the dorsal rostral anterior cingulate (family wise error corrected at p<0.04, T = 6.54, extent: 1,460 voxels) that overlapped with changes in blood flow. Given that gray matter reductions are unlikely following a single dose of medication these findings suggest that changes in blood flow are masquerading as reductions in gray matter on the T1-weighted scan irrespective of the temporal interval between baseline measures and longitudinal manipulations. These results underscore the crucial and immediate need to develop in vivo neuroimaging biomarkers for humans that can uniquely capture changes in neuronal structure dissociable from those related to blood flow or other physiological signals. PMID- 22302435 TI - "If we're going to change things, it has to be systemic:" systems change in children's mental health. AB - Communities that undertake systems change in accordance with the system of care philosophy commit to creating new systems entities for children and adolescents with serious emotional disturbance. These new entities are values-based, voluntary, and cross-agency alliances that include formal child-serving entities, youth, and families. Describing the scope and intent of one such implementation of systems of care, a mental health administrator commented, "If we're going to change things, it has to be systemic" (B. Baxter, personal communication, December 2, 2005). This paper explores the concept of "systemic" in the context of systems of care. Systems theory is used to understand strategies of purposeful systems change undertaken by stakeholders in established system of care communities. The paper presents a conceptual model of systems change for systems of care that is grounded in data from a national study of system of care implementation (Research and Training Center for Children's Mental Health in Case Studies of system implementation: Holistic approaches to studying community-based systems of care: Study 2, University of South Florida, Louis de la Parte Florida Mental Health Institute, Research and Training Center for Children's Mental Health, Tampa, FL, 2004). The model is based on Soft Systems Methodology, an application of systems theory developed to facilitate practical action around systems change in human systems (Checkland in Systems thinking, systems practice, Wiley, Chichester, 1999). The implications of these findings to real world actions associated with systems change in systems of care are discussed. PMID- 22302436 TI - Fostering marginalized youths' political participation: longitudinal roles of parental political socialization and youth sociopolitical development. AB - This study examines the roles of parental political socialization and the moral commitment to change social inequalities in predicting marginalized youths' (defined here as lower-SES youth of color) political participation. These issues are examined by applying structural equation modeling to a longitudinal panel of youth. Because tests of measurement invariance suggested racial/ethnic heterogeneity, the structural model was fit separately for three racial/ethnic groups. For each group, parental political socialization: discussion predicted youths' commitment to produce social change and for two groups, longitudinally predicted political participation. This study contributes to the literature by examining civic/political participation among disparate racial/ethnic groups, addresses an open scholarly question (whether youths' commitment to create social change predicts their "traditional" participation), and emphasizes parents' role in fostering marginalized youths' civic and political participation. PMID- 22302437 TI - Low-power upconversion in dye-doped polymer nanoparticles. AB - Examples of nanoscale low-power upconverting systems are rapidly increasing because of their potential application in numerous areas such as bioimaging or drug delivery. The fabrication of dye-doped cross-linked rubbery nanoparticles that exhibit upconversion even at relatively low power densities is reported here. The nanoparticles were prepared by surfactant-free emulsion polymerization of n-butylacrylate with divinylbenzene as a cross-linker, followed by dyeing of the resulting particles with a two-chromophore system composed of a palladium porphyrin sensitizer, and diphenylanthracene. Blue emission (~440 nm) of these systems was observed upon excitation at 532 nm. In addition to their optical properties, the particles were characterized by electron microscopy and dynamic light scattering. PMID- 22302438 TI - Reduced graphene oxide-mediated growth of uniform tin-core/carbon-sheath coaxial nanocables with enhanced lithium ion storage properties. AB - Tin-core/carbon-sheath coaxial nanocables directly integrated into a reduced graphene oxide (RGO) surface are constructed by a new strategy involving a RGO mediated procedure. The as-synthesized nanocables, with uniform diameter and high aspect ratio, are versatile and exhibit excellent lithium storage properties, as revealed by electrochemical evaluation. PMID- 22302439 TI - Anti-Xa Levels 4 h After Subcutaneous Administration of 5,700 IU Nadroparin Strongly Correlate with Lean Body Weight in Morbidly Obese Patients. AB - BACKGROUND: Morbidly obese patients (BMI > 40 kg/m(2)) are at increased risk for venous thromboembolism, especially after surgery. Despite limited evidence, morbidly obese patients are often administered a double dose of nadroparin for thromboprophylaxis compared to non-obese patients. The aim of this study was to evaluate the influence of different body size descriptors on anti-Xa levels after a double dose of nadroparin (5,700 IU) in morbidly obese patients. METHODS: In 27 morbidly obese patients with a mean total body weight of 148 kg (range 107-260 kg), anti-Xa levels were determined peri-operatively until 24 h after administration of a subcutaneous dose of 5,700 IU of nadroparin. RESULTS: Anti-Xa level 4 h after administration (A(4h), mean 0.22 +/- 0.07 IU/ml) negatively correlated strongly with lean body weight (r = -0.66 (p < 0.001)) and moderately with total body weight (r = -0.56 (p = 0.003)) and did not correlate with body mass index (r = -0.26 (p = 0.187)). The area under the anti-Xa level-time curve from 0 to 24 h (AUA(0-24h), mean 2.80 +/- 0.97 h IU/ml) correlated with lean body weight (r = -0.63 (p = 0.007)), but did not correlate with total body weight (r = -0.44 (p = 0.075)) or body mass index (r = -0.10 (p = 0.709)). CONCLUCIONS: Following a subcutaneous dose of nadroparin 5,700 IU, A(4h) and AUA(0-24h) were found to negatively correlate strongly with lean body weight. From these results, individualized dosing of nadroparin based on lean body weight should be considered in morbidly obese patients. PMID- 22302440 TI - In vitro Candida albicans biofilm induced proteinase activity and SAP8 expression correlates with in vivo denture stomatitis severity. AB - Denture stomatitis is a common inflammatory disorder of the palatal mucosa amongst denture wearers. The pathological changes are induced by Candida albicans biofilm on the fitting surface of the upper denture, and different individuals experience different levels of disease. C. albicans is known to produce secreted aspartyl proteinases (SAPs) to aid adhesion, invasion and tissue destruction. We hypothesised that differential expression and activity of SAPs from denture stomatitis isolates results in different levels of disease amongst denture wearers. We selected C. albicans isolates from asymptomatic controls and three different severities of disease [Newton's type (NT) 0, I, II and III]. We assessed biofilm formation and proteinase activity for each biofilm and investigated the transcriptional profile of SAPs 1, 2, 5, 6 and 8 from early (12 h) and mature (24 h) biofilms. There were no significant differences between isolates with respect to biofilm formation, whereas proteinase activity normalised to biofilm growth was significantly increased in the diseased groups (p < 0.0001). Proteinase activity correlated strongly with SAP expression (p < 0.0001). SAP8 expression was the greatest, followed by SAP5, 6, 2 and 1. The diseased groups showed the greatest levels of SAP expression, with significant differences also observed between the groups (p < 0.005). All SAPs except SAP5 were expressed in greater amounts in the mature biofilms compared to early biofilms. Overall, this study suggests that SAP activity in biofilms determined in vitro may help to explain differences in disease severity. SAP8 has been shown for the first time to play a prominent role in biofilms. PMID- 22302441 TI - Solid-state NMR [13C,15N] resonance assignments of the nucleotide-binding domain of a bacterial cyclic nucleotide-gated channel. AB - Channels regulated by cyclic nucleotides are key signalling proteins in several biological pathways. The regulatory aspect is conferred by a C-terminal cyclic nucleotide-binding domain (CNBD). We report resonance assignments of the CNBD of a bacterial mlCNG channel obtained using 2D and 3D solid-state NMR under Magic angle Spinning conditions. A secondary chemical shift analysis of the 141 residue protein suggests a three-dimensional fold seen in earlier X-ray and solution state NMR work and points to spectroscopic polymorphism for a selected set of resonances. PMID- 22302442 TI - Predictive power to assist phase 3 go/no go decision based on phase 2 data on a different endpoint. AB - One of the most critical decision points during drug development is to make a phase 3 go/no go decision after a phase 2 proof of concept trial is conducted. It is particularly challenging in oncology drug development where oftentimes the primary endpoint for phase 3 trial is overall survival (OS), but the phase 2 proof of concept trial is powered only for an early endpoint, typically progression-free survival (PFS), whose relationship to OS is often unclear. We propose the use of predictive power to assist the phase 3 go/no go decision by evaluating the strength of actual observed phase 2 efficacy effects in terms of how likely it will predict the chance of OS success in the subsequent phase 3 trial. The formula is provided for calculation of predictive power based on either observed PFS effect only, or observed OS effect only, or both. An example is provided to compare these three predictive powers, which shows that when there is little prior information about PFS and OS, the predictability based on the observed phase 2 PFS effect is low and not sensitive to the size of the trial and extent of the observed PFS effect, and it also has limited added value to the predictability based on the observed phase 2 OS effect. Therefore, one should be cautious of inherently high risk of making a phase 3 go/no go decision based on phase 2 PFS outcome alone and should take the phase 2 OS data into consideration whenever possible. PMID- 22302443 TI - Nerve conduits for nerve repair or reconstruction. AB - Advances in treating peripheral nerve lesions have resulted from research in nerve regeneration and the use biomaterials as well as synthetic materials. When direct tensionless repair of peripheral nerve lesions is not possible, nerve conduits may be used to bridge digital sensory nerve gaps of <=3 cm. Nerve autograft is the benchmark for larger, longer, mixed, or motor nerve defects. Biologic, autogenous conduits-typically veins or, rarely, arteries-have demonstrated their utility in nerve gaps <3 cm in length. Three types of bioabsorbable conduit have been approved by the US Food and Drug Administration, constructed of collagen, polyglycolic acid, or caprolactone. Caprolactone conduits have been found to be equivalent in results to autograft. Collagen conduits are next best, and polyglycolic acid conduits are functionally inferior. Further research and prospective, multicenter, large-scale trials are needed to help establish the role of synthetic, bioabsorbable conduits in peripheral nerve reconstruction. PMID- 22302444 TI - Management of supracondylar humerus fractures in children: current concepts. AB - Supracondylar humerus fractures are the most common elbow fractures in the pediatric population. Type I fractures are managed nonsurgically, but most displaced injuries (types II, III, and IV) require surgical intervention. Closed reduction and percutaneous pinning remains the mainstay of surgical management. Numerous studies have reported recent alterations in important aspects of managing these fractures. Currently, many surgeons wait until 12 to 18 hours after injury to perform surgery provided the child's neurovascular and soft tissue statuses permit. Increasingly, type II fractures are managed surgically; cast management is reserved for fractures with extension displacement only. Two to three lateral pins are adequate for stabilizing most fractures. Evolving management concepts include those regarding pin placement, the problems of a pulseless hand, compartment syndrome, and posterolateral rotatory instability. PMID- 22302445 TI - Factitious disorders of the upper extremity. AB - Factitious disorders of the upper extremity can manifest in many different forms; therefore, it is critical to recognize warning signs in the history and examination indicating that the patient may be creating the symptoms and physical manifestations of the presenting illness. These disorders present in such predictable patterns as lymphedema, Secretan syndrome, ulcerations and wound manipulation, clenched fist, subcutaneous emphysema, pachydermodactyly, nail deformities, and self-mutilation. Management recommendations include assigning therapeutic responsibility to one person and the involvement of a multidisciplinary team. Thorough documentation is essential for the protection of both the patient and the treating physician. Treatment of patients with factitious disorders of the upper extremity requires patience and insight to avoid being manipulated into performing unnecessary surgical procedures. PMID- 22302446 TI - Biomechanical testing of fracture fixation constructs: variability, validity, and clinical applicability. AB - Biomechanical testing of fracture fixation implants is crucial in preclinical evaluation and in comparing new devices with standard devices. Many variables must be considered when planning and implementing a biomechanical in vitro experiment. The type of test selected (eg, load-to-failure, stiffness, cyclic fatigue) depends on the research question being asked. For example, cyclic fatigue testing attempts to replicate clinical situations; thus, the load magnitudes and directions and the number of cycles should be decided accordingly. Most important, each bone and region of bone experiences specific in vivo forces based on muscular and other forces. Debate persists regarding whether cadaver or synthetic bone is optimal. The use of either material in biomechanical testing should be carefully considered and justified in the context of the study hypothesis. Appropriate study design is the main factor that affects the clinical applicability of the findings and the accuracy of the conclusions. PMID- 22302447 TI - Contributing factors to surgical site infections. AB - Surgical site infections (SSIs) are the most common nosocomial infections. These complications lead to revision surgery, delayed wound healing, increased use of antibiotics, and increased length of hospital stay, all of which have a significant impact on patients and the cost of health care. Such intraoperative factors as proper skin preparation, adherence to sterile technique, surgical duration, and traffic in the operating room contribute more to SSIs than do patient-related risk factors such as diabetes mellitus, obesity, and preexisting colonization with methicillin-resistant Staphylococcus aureus. Surgeons have a responsibility to understand the current evidence regarding the factors that affect the rates of SSIs so as to provide the highest level of patient care. PMID- 22302448 TI - Postarthroscopic glenohumeral chondrolysis. AB - Postarthroscopic glenohumeral chondrolysis (PAGCL) is a rare complication in which the articular cartilage of the shoulder undergoes rapid, degenerative changes shortly after arthroscopic surgery. Patients with PAGCL are often young (eg, aged 10 to 40 years) and develop deep shoulder pain with progressive loss of motion that begins months after the initial arthroscopic surgery. PAGCL should be considered in the differential diagnosis in the patient with deep, unexplained shoulder pain following arthroscopic surgery. Although the etiology of PAGCL is not yet fully understood, the pathophysiology is likely multifactorial. Inherent patient factors and risk factors for PAGCL have been identified, but it is unclear how these factors interact. Current surgical practices need to be examined and new practices developed to prevent PAGCL. Proud placement of nonabsorbable suture anchors during surgery to correct instability, as well as the use of thermal devices and intra-articular pain pumps, should be avoided. PMID- 22302449 TI - Adult Scheuermann kyphosis: evaluation, management, and new developments. AB - Scheuermann kyphosis is a structural hyperkyphosis defined radiographically as anterior wedging of >=5 degrees of at least three consecutive vertebral bodies. Typically, the disease develops during adolescence but may not present until adulthood. The etiology remains unknown. Indications for management include progressive deformity, pain, cosmesis, neurologic deficit, and cardiopulmonary compromise. Surgical intervention is indicated in patients with persistent pain and unacceptable deformity caused by significant kyphosis. Surgery can be performed through posterior-only, anterior-only, or combined anterior-posterior approaches. Correction should include the entire length of the kyphosis and should not exceed 50% of the original deformity. The most common postoperative complications are wound infection and loss of correction. PMID- 22302451 TI - Removing hexazinone from groundwater with microbial bioreactors. AB - Hexazinone, a triazine herbicide that is often detected as a ground and surface water contaminant, inhibits electron transport in photosynthetic organisms and is toxic to primary producers that serve as the base of the food chain. This laboratory study evaluated the ability of two types of microbial reactors, i.e., a vegetable oil-based nitrogen-limiting biobarrier and an aerobic slow sand filter, as methods for removing hexazinone from simulated groundwater. The N limiting biobarriers degraded hexazinone, but did so with a 52 week incubation period and a removal efficiency that varied greatly among replicates, with one biobarrier showing a removal efficiency of ~95% and the other an efficiency of ~50%. More consistent degradation was obtained with the aerobic sand biobarriers. Four aerobic biobarriers were evaluated and all behaved in a similar manner degrading hexazinone with removal efficiencies of ~97%; challenging two of the aerobic biobarriers with large amounts of influent hexazinone showed that these barriers are capable of efficiently remediating large amounts (>100 mg L(-1)) of hexazinone at high efficiency. The remediation process was due to biological degradation rather than abiotic processes. The long lag phase observed in both types of reactors suggests that an acclimation process, where microorganisms capable of degrading hexazinone increased in numbers, was required. Also, the isolation of bacteria that show a positive growth response to the presence of hexazinone in their growth media suggests biological degradation. PMID- 22302452 TI - High growth rate downregulates fumA mRNA transcription but is dramatically compensated by its mRNA stability in Escherichia coli. AB - Little is known about the association among the transcription, post transcription, and protein production of the fumA gene. This study demonstrates that increasing growth rate (k) from 0.24/h to 0.96/h causes a marked eightfold reduction in fumA transcription as assessed using the beta-galactosidase activity from fumA promoter fused with a lacZ reporter. It was further confirmed using Northern blot analysis. Most interestingly, the FumA protein levels remained unchanged over the growth rate, as indicated by Western blot analysis. Therefore, whether the reduced fumA mRNA expression under the high growth rate can be overcome by increasing the stability of the fumA mRNA was tested. The half-life of fumA mRNA was established to significantly increase by fivefold when the growth rate was increased to 0.96/h. This finding suggests that the cells could turn down the expression of fumA mRNA because of increased stability of its mRNA under the high growth rate. This notion indicates that mRNA stability plays an essential role in maintaining a critical cellular level of a given protein when the mRNA transcript is downregulated by a metabolic event. PMID- 22302453 TI - Effect of nonsurgical periodontal therapy and strict plaque control on preterm/low birth weight: a randomized controlled clinical trial. AB - OBJECTIVE: This randomized controlled clinical trial was carried out to assess the effect of comprehensive nonsurgical periodontal treatment and strict plaque control performed during pregnancy on the reduction of preterm and/or low birth weight rates (PTLBW). MATERIAL AND METHODS: Three hundred and three women were randomly allocated to receive periodontal treatment either during pregnancy (n = 147, test group) or after delivery (n = 156, control group). During pregnancy, the control group received only one session of supragingival scaling and oral hygiene instruction. In contrast, the test group received comprehensive periodontal treatment including multiple sessions of scaling and root planing, oral hygiene instructions, and frequent maintenance visits. RESULTS: At baseline, periodontal inflammation was observed in approximately 50% of sites and attachment loss affected <15% of sites. Compared to controls, women in the test group had significant reductions in the percentage of sites with plaque (48.5% vs. 10.3%, p < 0.001), gingival bleeding (23.3% vs. 2.5%, p < 0.001), calculus (21.3% vs. 4.1%, p < 0.001), bleeding on probing (38.1% vs. 2.6%, p < 0.001) and probing depth >=3 mm (19.97% vs. -2.45%, p < 0.001). No significant differences were observed between the groups in the occurrence of PT (11.7% vs. 9.1%, p = 0.57), LBW (5.6 % vs. 4.1%, p = 0.59), and PTLBW (4.15% vs. 2.60%, p = 0.53). CONCLUSIONS: Comprehensive periodontal treatment and strict plaque control significantly improved periodontal health; however, no reduction of PTLBW rates was observed. Thus, remaining periodontal inflammation posttreatment cannot explain the lack of effect of periodontal treatment on PTLBW. Clinical relevance This study demonstrated that periodontal diseases may be successfully treated during pregnancy. Our results do not support a potential beneficial effect of periodontal treatment on PTLBW. PMID- 22302454 TI - Accuracy of transfer of bite recording to simulated prosthetic reconstructions. AB - OBJECTIVES: A key aspect of complex restorative therapy is reconstruction of a new three-dimensional jaw relation. The objective of this study was to test the hypotheses that the initially recorded jaw relation would deviate substantially from the jaw position of the prosthetic reconstruction and that activity ratios of the jaw muscles would be significantly different for each of these jaw positions. MATERIALS AND METHODS: In 41 healthy subjects, 41 examiners incorporated intraoral occlusal devices fabricated with all the technical details and procedures commonly used during prosthetic reconstructions. The jaw positions in centric relation with the incorporated occlusal devices were telemetrically measured in the condylar, first molar and incisal regions, relative to intercuspation. Electromyographic (EMG) activity of the temporalis and masseter muscles was recorded, and activity ratios were calculated for homonymous and heteronymous muscles. RESULTS: The recorded jaw relation differed significantly (p < 0.001) from the jaw position reconstructed with the intraoral occlusal devices. The initially recorded jaw relation was reproduced with the intraoral occlusal device with spatial accuracy of approximately 0.3 mm in the condylar, molar and incisal regions. The EMG ratios between centric relations and the reconstructed positions were significantly different (p < 0.05) for the temporal muscle and the temporalis/masseter ratio. CONCLUSIONS: The findings revealed that three-dimensional jaw-relation recording may be reproduced in a simulated prosthetic reconstruction within the accuracy reported for replicate intraoral bite recordings. CLINICAL RELEVANCE: Centric relation recordings may be reproduced in a prosthetic reconstruction with the spatial accuracy of 0.3 mm. PMID- 22302455 TI - Assessing health-related quality of life of Chinese-American breast cancer survivors: a measurement validation study. AB - BACKGROUND: This study reports on the internal consistency and construct validity of the Functional Assessment of Cancer Therapy - General (FACT-G v.4) and 12-item Short Form Health Survey (SF-12 v.2) health-related quality of life (HRQOL) instruments with Chinese-American breast cancer survivors (BCS). METHODS: Participants completed mailed questionnaires at baseline and 12-month follow-up. HRQOL was measured using the FACT-G and the SF-12. The measures were evaluated by construct validity and reliability tests. Factor analyses were performed in a two wave assessment through exploratory and confirmatory analyses at baseline and follow-up. RESULTS: Seventy-four Chinese-American BCS participated. Excellent internal consistency (alpha > 0.85) and good construct validity for the FACT-G (five factors) and the SF-12 (two factors) were observed. Factor structure of both measures accounted for 70% of the common variance in physical, social/family, emotional, and functional well-being subscales for the FACT-G and in physical and mental components for the SF-12. CONCLUSIONS: Our data demonstrated good internal consistency and construct validity of the measures. The psychometric findings demonstrate the utility of the FACT-G and the SF-12 to assess HRQOL among Chinese-American BCS. PMID- 22302456 TI - Ophthalmic features of CHARGE syndrome with CHD7 mutations. AB - Coloboma and various ocular abnormalities have been described in CHARGE syndrome, although the severity of visual impairment varies from case to case. We conducted a multicenter study to clarify the ophthalmic features of patients with molecularly confirmed CHARGE syndrome. Thirty-eight eyes in 19 patients with CHARGE syndrome and confirmed CHD7 mutations treated at four centers were retrospectively studied. Colobomata affected the posterior segment of 35 eyes in 18 patients. Both retinochoroidal and optic disk colobomata were bilaterally observed in 15 patients and unilaterally observed in 3 patients. The coloboma involved the macula totally or partially in 21 eyes of 13 patients. We confirmed that bilateral large retinochoroidal colobomata represents a typical ophthalmic feature of CHARGE syndrome in patients with confirmed CHD7 mutations; however, even eyes with large colobomata can form maculas. The anatomical severity of the eye defect was graded according to the presence of colobomata, macula defect, and microphthalmos. A comparison of the severity in one eye with that in the other eye revealed a low-to-moderate degree of agreement between the two eyes, reflecting the general facial asymmetry of patients with CHARGE syndrome. The location of protein truncation and the anatomical severity of the eyes were significantly correlated. We suggested that the early diagnosis of retinal morphology and function may be beneficial to patients, since such attention may determine whether treatment for amblyopia, such as optical correction and patching, will be effective in facilitating the visual potential or whether care for poor vision will be needed. PMID- 22302457 TI - Functions and outcomes of a clinical medical ethics committee: a review of 100 consults. AB - CONTEXT: Established in 1997, Summa Health System's Medical Ethics Committee (EC) serves as an educational, supportive, and consultative resource to patients/families and providers, and serves to analyze, clarify, and ameliorate dilemmas in clinical care. In 2009 the EC conducted its 100th consult. In 2002 a Palliative Care Consult Service (PCCS) was established to provide supportive services for patients/families facing advanced illness; enhance clinical decision making during crisis; and improve pain/symptom management. How these services affect one another has thus far been unclear. OBJECTIVES: This study describes EC consults: types, reasons, recommendations and utilization, and investigates the impact the PCCS may have on EC consult requests or recommendations. METHODS: Retrospective reviews of 100 EC records explored trends and changes in types of consults, reasons for consults, and EC recommendations and utilization. RESULTS: There were 50 EC consults each in the 6 years pre- and post-PCCS. Differences found include: (1) a decrease in number of reasons for consult requests (133-62); (2) changes in top two reasons for EC consult requests from 'Family opposed to withdrawing life-sustaining treatment (LST)' and 'Patient capacity in question' to 'Futility' and 'Physician opposed to providing LST'; (3) changes in top two recommendations given by the EC from 'Emotional Support for Patient/Family' and 'Initiate DNR Order' to 'Comfort Care' and 'Withdraw Treatment.' Overall, 88% of recommendations were followed. CONCLUSION: PCCS availability and growth throughout the hospital may have influenced EC consult requests. EC consults regarding family opposition to withdrawing LST and EC recommendations for patient/family support declined. PMID- 22302458 TI - RSV hospitalisation and healthcare utilisation in moderately prematurely born infants. AB - Respiratory syncytial virus (RSV) infection is associated with chronic respiratory morbidity in infants born very prematurely. Our aims were to determine if infants born moderately prematurely (32--35 weeks of gestation) who had had an RSV hospitalisation, compared to those who had not, had greater healthcare utilisation and related cost of care in the first 2 years. Two thousand and sixty-six eligible infants' records were examined to identify three groups: 20 infants admitted for an RSV lower respiratory tract infection (RSV), 30 admitted for another respiratory problem (other respiratory) and 108 admitted for a nonrespiratory problem/never admitted (non-respiratory).Healthcare utilisation was assessed by examining hospital and general practitioner records and cost of care calculated using the National Scheme of Reference costs and the British National Formulary prices. The mean cost of care in the RSV group (L12,505) was greater than the non-respiratory(L1,178) (95% CI for difference L5,015 to L17,639, p=00.002) and the other respiratory (L3,356) groups (95% CI for difference L2,963 to L15,606, p<0.001). The adjusted mean differences in the cost of care were L11,186 between the RSV and non-respiratory groups (95% CI L4,763 to L17,609) and L9,076 (95% CI L2,515 to L15,637) between the RSV and the other respiratory groups. Forty-two of 2,066 eligible infants had an RSV hospitalisation (2%);thus, assuming prophylaxis would reduce the hospitalisation rate by 50%, the number needed to treat was 98. In conclusion,RSV hospitalisation in moderately prematurely born infants is associated with increased health related cost of care. Nevertheless, if RSV prophylaxis is to be cost effective,a high risk group of moderately prematurely born infants needs to be identified. PMID- 22302459 TI - Double-blind, placebo-controlled trial on the effect of piracetam on breath holding spells. AB - Breath-holding spells (BHS) are apparently frightening events occurring in otherwise healthy children.The aim of this study was to evaluate the efficacy of piracetam in the treatment of breath-holding spells. Forty patients with BHS (who were classified into two groups)were involved in a double-blinded placebo controlled prospective study. Piracetam was given to group A while group B received placebo. Patients were followed monthly for a total period of 4 months. The numbers of attacks/month before and monthly after treatment were documented, and the overall number of attacks/month after treatment was calculated in both groups. The median number of attacks/month before treatment in the two groups was 5.5 and 5,respectively, while after the first month of treatment, it was 2 and 5, respectively. The median overall number of attacks/month after treatment in both groups was 1 and 5, respectively.There was a significant decline of number of attacks after piracetam treatment compared to placebo (p value<0.001). There were no reported side effects of the piracetam throughout the study period. In conclusion, piracetam is a safe and effective drug for the treatment of breath holding spells in children. PMID- 22302460 TI - A 2-month-old infant with vomiting, seizures, and progressive apathy. AB - A 2-month-old infant was admitted to hospital because of recurrent vomiting for 1 week, progressive apathy, and focal seizures. The cranial MRI showed a noticeable result. PMID- 22302461 TI - Cardiac malformation of partial trisomy 7p/monosomy 18p and partial trisomy 18p/monosomy 7p in siblings as a result of reciprocal unbalanced malsegregation- and review of the literature. AB - We report two unbalanced translocations involving the short arms of chromosomes 7 and 18 due to a balanced translocation 7;18 in the mother. Karyotyping and fluorescence in situ hybridization analysis of the female fetus revealed an unbalanced subtelomeric translocation(karyotype 46,XX,der(18)t(7;18)(p22.3;p11.32)mat resulting in a partial trisomy 7p and a partial monosomy 18p.Array comparative genomic hybridization (CGH) detected a4.44 Mb heterozygous duplication at 7p22.3 to 7p22.1 and a0.178-Mb heterozygous deletion at 18p11.32. Clinical characteristics comprised a mildly stenotic bicuspid aortic valve and a small aortic arch without coarctation. The patient's older brother displayed a reciprocal version of her chromosomal aberration (46,XY,der(7)t(7;18)(p22;p11.32) resulting in a partial monosomy 7p and a partial trisomy 18p. Array CGH revealed a 4.75-Mb heterozygous deletion at 7p22.3p22.1 and a 0.579-Mb duplication at 18p11.32. He presented with tetralogy of Fallot, cleft palate, microcephalus without craniosynostosis, growth retardation, ptosis of the right eyelid, right-sided renal agenesis, unilateral cryptorchism,and mental retardation. In this report, we present the clinical phenotype in patients with aberrations of chromosomes 7p and 18p and reviewed the literature to summarize cardiovascular malformations in these patients. PMID- 22302462 TI - Investigating the effect of dose rate and maximum allowable MLC leaf velocity in dynamic IMRT. AB - The purpose of this study is to analyze the effect of various dose rates (DR) and maximum allowable MLC leaf velocities (MLV) in dynamic Intensity Modulated Radiotherapy (IMRT) planning and delivery of head and neck patients. Five head and neck patients were retrospectively included in this study. The initial dynamic IMRT 'reference plans' were created for all these patients, using a DR of 400 MU/min and MLV of 2.5 cm/s. Additional plans were generated by varying the DR and MLV values. The DR value was varied from 100 to 600 MU/min, in increments of 100 MU/min, for a MLV of 2.5 cm/s. Also the MLV was varied from 0.5 to 3 cm/s, in increments of 0.5 cm, for a DR of 400 MU/min. In order to maintain the prescribed dose to the PTV, the DR was allowed to vary ('beam hold or DR modulation' during delivery) when the MLV was changed and the MLV was allowed to vary when the DR was changed. The mean doses to the PTV as well as parotids, maximum dose of spinal cord and total MU were recorded for analysis. The effect of DR and MLV on treatment delivery was analyzed using the portal dosimetry for all the above plans. The predicted portal dose fluences of the TPS were compared with the measured EPID fluences using gamma evaluation criteria of 2% dose difference and 2 mm distance to agreement. A small proportional increase in OAR doses with DR was observed. Increases to MLV value resulted in decreases of the OAR doses and this effect was considerable for values below 1.5 cm/s. DR and MLV both resulted in no appreciable dose variation to the target. The total MU to deliver the plan increases with increasing DR and decreasing MLV. When comparing portal images derived from the treatment plans with portal images obtained by delivering the treatments, it was observed that the treatments was most reliably delivered when the DRs were set to lower values and when the MLVs were set to higher values. PMID- 22302463 TI - Four dimensional CT imaging: a review of current technologies and modalities. AB - Organ motion is a substantial concern in the treatment of thoracic tumours using radiotherapy. A number of technologies have evolved in order to address this both during computed tomography (CT) imaging and radiation delivery. This review paper investigates the various technologies which have been developed in the field of CT scanning as well as their accuracy, cost and the implications of their clinical implementation. The scanning modalities covered include: slow CT, breath hold CT, gated CT and retrospectively correlated CT (4DCT). It was found that there are advantages and drawbacks to each of the mentioned techniques relating to patient dose, scan time, extra equipment and workload. Also some scanning techniques are only compatible with certain treatment modalities which would further influence the decision as to which technologies to implement. PMID- 22302464 TI - Digital chest radiography image quality assessment with dose reduction. AB - A retrospective study of digital chest radiography was performed to compare the image quality and dose parameters from two X-ray rooms in different areas of the same hospital using identical X-ray units but different local protocol for obtaining chest PA and lateral radiographs. Image quality of radiographs was assessed from the printed films using well established European guidelines and modified criteria. Patient entrance surface air kerma was calculated using technical data recorded for each radiograph and measured output of the X-ray unit. Effective dose and dose to radiosensitive organs was estimated using dose calculation software PCXMC. There was no statistical significant difference in the evaluated image quality using either technique, median entrance surface air kerma to the patient reduced significantly with added filtration technique and use of normal density setting. Phantom measurements indicated that an additional filtration of 0.1 mm Cu + 1 mm Al in the X-ray beam alone reduced the entrance surface air kerma by 35%. PMID- 22302465 TI - The Australian radiation protection and nuclear safety agency megavoltage photon thermoluminescence dosimetry postal audit service 2007-2010. AB - The Australian radiation protection and nuclear safety agency (ARPANSA) has continuously provided a level 1 mailed thermoluminescence dosimetry audit service for megavoltage photons since 2007. The purpose of the audit is to provide an independent verification of the reference dose output of a radiotherapy linear accelerator in a clinical environment. Photon beam quality measurements can also be made as part of the audit in addition to the output measurements. The results of all audits performed between 2007 and 2010 are presented. The average of all reference beam output measurements calculated as a clinically stated dose divided by an ARPANSA measured dose is 0.9993. The results of all beam quality measurements calculated as a clinically stated quality divided by an ARPANSA measured quality is 1.0087. Since 2011 the provision of all auditing services has been transferred from the Ionizing Radiation Standards section to the Australian Clinical Dosimetry Service (ACDS) which is currently housed within ARPANSA. PMID- 22302466 TI - Effect of Roux-en-Y gastric bypass on testosterone and prostate-specific antigen. AB - BACKGROUND: Obese men have lower serum levels of testosterone, dehydroepiandrosterone (DHEA) and prostate-specific antigen (PSA), but an increased risk of dying from prostate cancer. The aim of this study was to examine the effect of surgically induced weight loss on serum testosterone, DHEA and PSA levels in obese men. METHODS: Consecutive men undergoing Roux-en-Y gastric bypass (RYGB) participated in a prospective, longitudinal study. Main outcomes were changes were body mass index (BMI), percentage excess weight loss, serum levels of testosterone, DHEA and PSA, PSA mass and plasma volume, measured before operation and 3, 6 and 12 months later. RESULTS: In 64 patients, mean BMI fell from 48.2 kg/m(2) before operation to 39.2, 35.6 and 32.4 kg/m(2) at 3, 6 and 12 months after RYGB. Testosterone levels rose significantly from 259 ng/dl to 386, 452 and 520 ng/dl respectively. Serum PSA levels increased significantly from 0.51 ng/ml to 0.67 ng/ml at 12 months. There were no significant changes in DHEA or PSA mass. CONCLUSION: RYGB normalizes the serum testosterone level. PSA levels increase with weight loss and may be inversely correlated with changes in plasma volume, indicating that PSA levels may be artificially low in obese men owing to haemodilution. PMID- 22302468 TI - Komagataella populi sp. nov. and Komagataella ulmi sp. nov., two new methanol assimilating yeasts from exudates of deciduous trees. AB - Two new species of the methanol assimilating ascosporic yeast genus Komagataella are described. Komagataella populi sp. nov. (NRRL YB-455, CBS 12362, type strain, MycoBank accession number = 564110) was isolated from an exudate on a cottonwood tree (Populus deltoides), Peoria, Illinois, USA, and Komagataella ulmi sp. nov. (NRRL YB-407, CBS 12361, type strain, MycoBank accession number = 564111) was isolated from the exudate on an elm tree (Ulmus americana), also growing in Peoria, Illinois. The species were resolved from divergence in gene sequences for domains D1/D2 LSU rRNA, ITS1-5.8S-ITS2, mitochondrial small subunit rRNA, RNA polymerase subunit 1 and translation elongation factor-1alpha. Species of Komagataella assimilate few carbon compounds and are unlikely to be resolved from differences in standard growth and fermentation tests. For this reason, separation of species is dependent on gene sequence analysis. PMID- 22302469 TI - Preparation of responsive micrometer-sized microgel particles with a highly functionalized shell. AB - We describe a facile approach for the synthesis of micrometer-sized (~3.5 MUm), pH-responsive microgel particles, which have functional carboxylic acid groups concentrated in the shell. The large size offers the possibility to directly study the interactions between individual, isolated microgel particles with active ingredients by optical microscopy. Our results show that the synthesized microgel particles can load and release active ingredients via changing pH values. The complexation of Ca(2+) with the -COOH functional groups located at the microgel surfaces not only regulates the active ingredient's uptake efficiency, but also provides a novel way to reveal the spatial distribution of the functional groups inside the microgel particles. PMID- 22302470 TI - A pathway analysis method for genome-wide association studies. AB - For genome-wide association studies, we propose a new method for identifying significant biological pathways. In this approach, we aggregate data across single-nucleotide polymorphisms to obtain summary measures at the gene level. We then use a hierarchical Bayesian model, which takes the gene-level summary measures as data, in order to evaluate the relevance of each pathway to an outcome of interest (e.g., disease status). Although shifting the focus of analysis from individual genes to pathways has proven to improve the statistical power and provide more robust results, such methods tend to eliminate a large number of genes whose pathways are unknown. For these genes, we propose to use a Bayesian multinomial logit model to predict the associated pathways by using the genes with known pathways as the training data. Our hierarchical Bayesian model takes the uncertainty regarding the pathway predictions into account while assessing the significance of pathways. We apply our method to two independent studies on type 2 diabetes and show that the overlap between the results from the two studies is statistically significant. We also evaluate our approach on the basis of simulated data. PMID- 22302471 TI - Prognostic factors in patients aged 50 years or older undergoing allogeneic hematopoietic stem cell transplantation for hematologic malignancy. AB - We retrospectively analyzed patients aged C 50 years with hematologic malignancies who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) to identify preoperative variables predicting the outcome. There were 71 patients with a median age of 57 years (range: 50-63 years) who had acute leukemia (n = 53) or myelodysplastic syndrome (n = 18). Myeloablative conditioning was done in 35 patients and 36 patients had reduced-intensity conditioning. The 5-year overall survival rate (OS), cumulative relapse rate, and non-relapse mortality rate (NRM) were 45, 24, and 33%, respectively. According to multivariate analysis, high-risk disease (HR 3.50, 95% CI 1.43-8.56, P = 0.006), a hematopoietic cell transplantation comorbidity index (HCT-CI) score >= 3 (HR 4.41, 95% CI 1.31-14.77, P = 0.016), and an HLA-mismatched unrelated donor (HR 4.03, 95% CI 1.46-11.10, P = 0.007) were significant predictors of worse OS. Highrisk disease was also significantly associated with a higher cumulative relapse rate (HR 4.59, 95% CI 0.94-6.92, P = 0.065). Furthermore, an HCT-CI score >= 3 (HR 3.02, 95% CI 1.01-20.78, P = 0.048) and an HLA-mismatched unrelated donor (HR 3.02, 95% CI 1.04-8.74, P = 0.042) were risk factors for NRM. These results suggest that the disease risk, HCT-CI score, and donor type/histocompatibility are prognostic factors for elderly patients, while the conditioning regimen and age are not predictors. PMID- 22302472 TI - Synthesis and characterization of a thermoresponsive polyoxometalate-polymer hybrid. AB - We report the synthesis of the first organo-POM with thermoresponsive properties. Our concept will provide chemists with a new tool to design POMs whose solubility is reversibly controllable through an external stimulus. POM-polymer TBA(7)[POM] poly(N,N-diethylacrylamide) (POM-PDEAAm), was prepared by grafting PDEAAm-NH(2) (obtained by RAFT polymerization) onto the activated Dawson acyl-POM, alpha(2) [P(2)W(17)O(61)SnCH(2)CH(2)C(=O)](6-). Extensive MS analysis was used to monitor the chain-functionalization steps and to confirm the formation of the hybrid. Aqueous solutions of the (NH(4))(7)[POM-PDEAAm] exhibited a LCST of 38 degrees C. Thus, the solubility/aggregation of the hybrid was reversibly controlled by changing the temperature. Above 38 degrees C, the solution became cloudy, and cleared again upon cooling. Dynamic light scattering (DLS) revealed the formation of small aggregates in the range 100 nm. We assumed that the charged POM head units prevented the formation of the larger-scattering aggregates that are usually observed for PDEAAm, and promoted the formation of micelle-like structures. The conjugate exhibited a temperature transition, which was different from that of the polymer and depended on the counterions associated with the POM. This result demonstrates the potential for merging organic (in this case, polymer) and inorganic structures to afford materials that exhibit new properties. PMID- 22302473 TI - Reconstruction of extended Petri nets from time-series data by using logical control functions. AB - The aim of this work is to extend a previously presented algorithm (Durzinsky et al. 2008b in Computational methods in systems biology, LNCS, vol 5307. Springer, Heidelberg, pp 328-346; Marwan et al. 2008 in Math Methods Oper Res 67:117-132) for the reconstruction of standard place/transition Petri nets from time-series of experimental data sets. This previously reported method finds provably all networks capable to reproduce the experimental observations. In this paper we enhance this approach to generate extended Petri nets involving mechanisms formally corresponding to catalytic or inhibitory dependencies that mediate the involved reactions. The new algorithm delivers the set of all extended Petri nets being consistent with the time-series data used for reconstruction. It is illustrated using the phosphate regulatory network of enterobacteria as a case study. PMID- 22302474 TI - Normal variation in behavioral adjustment relates to regional differences in cortical thickness in children. AB - Neuroanatomical correlates of developmental psychopathology such as attention deficit hyperactivity and conduct disorder have been identified. The majority of studies point to lesser gray matter in psychopathology,often involving prefrontal cortices. The goal of this study was to test whether similar neural correlates exist for behavioral variance in healthy children and adolescents. A large sample (n = 106) aged 8-19 years underwent MR scanning and their parents completed the Strength and Difficulties Questionnaire. The relationships between cortical thickness and conduct problems and hyperactivity/inattention scale scores were investigated throughout the cerebrum. No associations were found between normal variance in hyperactivity/inattention and cortical thickness.Normal variance in conduct problems was associated with thinner left hemisphere prefrontal and supramarginal cortices. Relationships between conduct problems and cortical thickness interacted with age, with the greatest differences in cortical thickness seen in the younger children. These interactions were observed in the anterior cingulate,orbitofrontal, middle and superior frontal, as well as lateral and medial temporal cortices. In conclusion, the results indicate neurobiological continuity between symptoms of conduct problems within the normal range, and conduct disorder. Relationships of thinner cortices and conduct problems were primarily seen in younger children, and appeared to decrease with age, indicative of different maturational trajectories in the groups. The long-term consequences are unknown, and the results point to a need for longitudinal studies of developmental trajectories of neuroanatomical foundations of behavioral adjustment. PMID- 22302475 TI - Child psychiatry and the developmental perspective. PMID- 22302476 TI - The importance of advanced parental age in the origin of neurofibromatosis type 1. AB - Von Recklinghausen neurofibromatosis (NF1) is an autosomal dominant disorder with a prevalence about 1/3,000 (1/2,000-1/5,000 in various population-based studies). About 30-50% of cases are sporadic, resulting from a new mutation. NF1 is fully penetrant by mid-childhood, stigmata, and medical problems (neurological, dermatological, endocrine, ophthalmological, oncological) are highly variable. Advanced paternal age (APA) has been known to increase the risk of new germline mutations that contribute to the presence of a variety of genetic diseases in the human population. The trend in developed countries has been toward higher parental age due to various reasons. In a cross-sectional study, in two university hospital centers, data on parental age of 103 children (41 female) born between 1976 and 2005 with sporadic NF1 were analyzed. Parental age at birth was compared with the Czech general population matched to birth year. The mean NF1 sporadic case paternal age at birth was 32.0 years (95% CI 30.7-33.3 years) compared with 28.8 years (95% CI 28.6-29.1 years) in the general population (P < 0.001). The mean maternal age at birth was 27.4 years (95% CI 26.3-28.5 years) compared with 25.8 years (95% CI 25.5-26.0 years) in the general population (P < 0.05). The case-control difference in the father's age was higher than it was for the mother's age. Sporadic NF1 cases accounted for 35.6% of our entire NF1 cohort. We confirmed an association of advanced parental and particularly paternal age with the occurrence of sporadic NF1. PMID- 22302477 TI - Variability in susceptibility of voles (Arvicolinae) to experimental infection with Cryptosporidium muris and Cryptosporidium andersoni. AB - The infectivity of Cryptosporidium muris and Cryptosporidium andersoni in various species of voles was studied using experimental infections. None of the experimental voles inoculated with 1 * 10(5) oocysts of Cryptosporidium spp. shed any oocysts during 40 DPI, except Brandt's vole (Lasiopodomys brandtii), which was susceptible to C. muris infection. Experiments confirmed the resistance of voles of the genus Microtus sensu stricto to infection with mammalian gastric cryptosporidia, which provides a new study model with prospects to more fully understand the processes involved in the phenomenon of host specificity of this group of protists. PMID- 22302478 TI - Biomarkers of antimony resistance: need for expression analysis of multiple genes to distinguish resistance phenotype in clinical isolates of Leishmania donovani. AB - Resistance to antimony is a major cause of failure to therapy in a large proportion of visceral leishmaniasis cases. Methods to distinguish resistant and sensitive parasite are urgently needed as the standard in vitro intracellular drug susceptibility assays are cumbersome and time consuming. Differential expression profiling studies have led to the identification of several antimony resistance-associated genes; however, their efficacy as a potential biomarker for monitoring antimony resistance remains imprecise. We analysed the expression of eight genes [antimony metabolism-associated genes - multidrug resistance protein A (MRPA), gamma-glutamylcysteine synthetase (gamma-GCS) and aquaporin-1 (AQP1) - and genes identified by proteome/transcriptome profiling-heat shock protein 83, mitogen-activated protein kinase 1 and histones H1, H2A and H4) in antimony resistant (n=10) and antimony-sensitive (n=4) clinical isolates of Leishmania donovani by quantitative real-time PCR, in comparison with a lab-generated resistant and a standard sensitive isolate. We observed a significant differential expression of MRPA, histone H1 (p<0.01), gamma-GCS, HSP83 (p<0.005) and histone H2A and H4 (p<0.0001) in a group of sodium antimony gluconate resistant isolates compared to sensitive isolates. Preferential AQP1 expression was observed in all the sensitive isolates (p<0.0001). Overall, expression profile in field isolates for all the genes studied showed altered expression in majority of isolates, while in some, the expression was static. All the isolates showed a mosaic of expression pattern of the genes analysed indicating constellation of genes contributes towards the drug susceptibility of parasite. As none of the genes exhibit an absolute correlation with phenotype, targeted expression analysis of a set of genes should be considered as biomarker for distinguishing the antimony-resistant and antimony-sensitive parasite. PMID- 22302479 TI - Immunolocalization of beta- and delta-giardin within the ventral disk in trophozoites of Giardia duodenalis using multiplex laser scanning confocal microscopy. AB - Immunolocalization of beta- and delta-giardin in Giardia duodenalis trophozoites revealed that both giardins are strictly associated with the ventral disk (VD). Optical sectioning of the immunolabeled VD, together with quantitative colocalization of delta- and beta-giardin immunoreactivity, demonstrated that delta-giardin is primarily localized to the ventral side, and beta-giardin is localized to the dorsal side of the VD. PMID- 22302480 TI - Camelina meal increases egg n-3 fatty acid content without altering quality or production in laying hens. AB - Camelina sativa is an oilseed plant rich in n-3 and n-6 fatty acids and extruding the seeds results in high protein meal (*40%) containing high levels of n-3 fatty acids. In this study, we examined the effects of feeding extruded defatted camelina meal to commercial laying hens, measuring egg production, quality, and fatty acid composition. Lohmann White Leghorn hens (29 weeks old) were randomly allocated to three dietary treatment groups (n = 25 per group) and data was collected over a 12 week production period. All the treatment groups were fed a corn soy based experimental diet containing 0% (control), 5, or 10% extruded camelina meal. We found no significant differences in percent hen-day egg production and feed consumed per dozen eggs. Egg shell strength was significantly higher in both camelina groups compared to the controls. Egg total n-3 fatty acid content increased 1.9- and 2.7-fold in 5 and 10% camelina groups respectively relative to the control. A similar increase in DHA content also occurred. Further camelina meal did not alter glucosinolate levels and no detectable glucosinolates or metabolic product isothiocyanates were found in the eggs from either the 5 or 10% camelina groups. These results indicate that camelina meal is a viable dietary source of n-3 fatty acids for poultry and its dietary inclusion results in eggs enriched with n-3 fatty acids. PMID- 22302481 TI - Intolerance of uncertainty, fear of anxiety, and adolescent worry. AB - A 5 year, ten wave longitudinal study of 338 adolescents assessed the association between two forms of cognitive vulnerability (intolerance of uncertainty and fear of anxiety) and worry. Multilevel mediational analyses revealed a bidirectional and reciprocal relation between intolerance of uncertainty and worry in which change in one variable partially explained change in the other. Fear of anxiety and worry also showed evidence of a bidirectional relation, although change in fear of anxiety had a much weaker mediational effect on change in worry than vice versa. The findings show that relative to fear of anxiety, intolerance of uncertainty may play a greater role in the etiology of worry in adolescents. PMID- 22302482 TI - Involvement of heme oxygenase-1 in Korean colon cancer. AB - Heme oxygenase-1 (HO-1) catabolizes heme into carbon monoxide, biliverdin, and free iron which mediate its protective effect against oxidative stress. The aim of the present study was to determine the expression level and activity of HO-1 in Korean colon cancer tissues and cell lines. HO-1 protein expression was higher (>1.5-fold) in tumor tissues than in adjacent normal tissues in 14 of 20 colon cancer patients, and HO-1 protein expression was closely correlated with HO-1 enzyme activity in cancer tissues. Immunohistochemical data confirmed that HO-1 protein was expressed at a higher level in colon cancer tissues than in normal mucosa. Furthermore, HO-1 mRNA and protein expression and enzyme activity were higher in the colon cancer cell lines Caco-2, SNU-407, SNU-1033, HT-29, and SW 403 than in the normal fetal human colon cell line FHC. Treatment with the HO-1 inhibitor zinc protoporphyrin decreased the viability of colon cancer cell lines. These data indicate that HO-1 may serve as a clinically useful biomarker of colon cancer and as a target for anticolon cancer drugs. PMID- 22302483 TI - Clinicopathological significance of cathepsin D expression in non-small cell lung cancer is conditional on apoptosis-associated protein phenotype: an immunohistochemistry study. AB - Cathepsin D is a well-known peptidase which belongs to the family of aspartic peptidases. It has been found to be overexpressed in many malignant tumors and associated with cancer metastasis and clinical outcome. However, its function in cancers remains controversial. Recently, increasing evidence shows that cathepsin D may play important roles in cell apoptosis. In the current study, we examined the expression of cathepsin D and a group of apoptosis-associated proteins including bcl-2, caspase 3, fas, fasL, p53, and survivin in nonsmall cell lung cancer (NSCLC) tissues to investigate the possible association between cathepsin D and these apoptosis-associated proteins and the clinicopathological features using immunohistochemistry. Cathepsin D expression was detected in cancer tissues including cancer cells (positive rate 64.5%(49/76)) and stromal parts including leukocytes, fibroblasts, capillary endothelial cells, and the matrix. No significant difference was found between the expression of cathepsin D in cancer cells and the corresponding non-tumor portions including bronchial epithelia and submucosal glands (positive rate 53.3% (8/15)) (p>0.05). Immunofluorescence study on formalin-fixed, paraffin-embedded specimens confirmed the cytoplasmic expression of cathepsin D in cancer cells and non-tumor portions. Western blot study detected both mature and immature forms of cathepsin D in lung and NSCLC tissues, while the expression level of neither form showed a significant difference between these tissues (p>0.05). Positive association was found between cathepsin D expression and fas status (p<0.01) but not with the other apoptosis associated proteins (p>0.05) in cancer cells. Cathepsin D expression alone was not associated with any of the clinicopathological features (p>0.05), while multiplemarker analysis revealed that two immunostaining phenotypes based on the expression of cathepsin D and one of the apoptosis-associated proteins, namely, cathepsin D+/caspase 3- and cathepsin D+/p53+ showed clinicopathological significance. The cathepsin D+/caspase 3- group was associated with advanced tumor node metastasis stages (III and IV) (p<0.05), while the cathepsin D+/p53+ group was associated with lymph node metastasis (p<0.05). The present findings indicate that the expression of cathepsin D in non-small cell lung cancer may have possible contributions to cancer development which is conditional on apoptosis-associated protein phenotype. PMID- 22302484 TI - Nuclisome--targeting the tumor cell nucleus. AB - The Nuclisome concept builds on a novel two-step targeting strategy with the aim to deliver short-range Auger-electron-emitting radionuclides to nuclear DNA of tumor cells. The concept is based on the use of Nuclisome-particles, i.e., tumor targeted PEG-stabilized liposomes loaded with a unique DNA-intercalating compound that enables specific and effective delivery of radionuclides to DNA. The specific and potent two-step targeting leads to eradication of tumor cells while toxicity to normal organs is reduced to a minimum. Results of in vitro and in vivo studies point towards the Nuclisome concept as a promising strategy for the treatment of small tumor masses and, in particular, for the elimination of spread single cells and micrometastases. PMID- 22302485 TI - Influence of attitudes towards change and self-directness on dropout in eating disorders: a 2-year follow-up study. AB - OBJECTIVE: This study examined dropout-related factors at the Outpatient Eating Disorders Treatment Programme. METHOD: One hundred ninety-six eating disorders patients following DSM-IV diagnostic criteria that consecutively commenced treatment were recruited and followed up for a 2-year period. A total of 151 patients completed the whole assessment with a set of questionnaires evaluating eating and general psychopathology. The Attitudes towards Change in Eating Disorders questionnaire was used, and personality was evaluated using the Temperament and Character Inventory. During the follow-up period, patients were re-assessed. Two years later, 102 patients continued on treatment. RESULTS: Scores on Precontemplation at the beginning were predictors for dropout at 2-year follow-up. Character variables, as Responsibility, Integrity and Self-acceptance were protective factors to be at Precontemplation stage. DISCUSSION: The clinician's challenge is to help eating disorders patients to develop an unyielding sense of responsibility and self-acceptance, aimed to integrate the therapeutic choice into their own intrapersonal frame of goals. PMID- 22302486 TI - Magnetic fields in Earth-like exoplanets and implications for habitability around M-dwarfs. AB - We present estimations of dipolar magnetic moments for terrestrial exoplanets using the Olson & Christiansen (EPS Lett 250:561-571, 2006) scaling law and assuming their interior structure is similar to Earth. We find that the dipolar moment of fast rotating planets (where the Coriolis force dominates convection in the core), may amount up to ~80 times the magnetic moment of Earth, M ?, for at least part of the planets' lifetime. For slow rotating planets (where the force of inertia dominates), the dipolar magnetic moment only reaches up to ~1.5 M [symbol in text]. Applying our calculations to confirmed rocky exoplanets, we find that CoRoT-7b, Kepler-10b and 55 Cnc e can sustain dynamos up to ~18, 15 and 13 M [symbol in text], respectively. Our results also indicate that the magnetic moment of rocky exoplanets not only depends on rotation rate, but also on their formation history, thermal state, age, composition, and the geometry of the field. These results apply to all rocky planets, but have important implications for the particular case of planets in the Habitable Zone of M-dwarfs. PMID- 22302487 TI - Wanted: dead or alive? Isotopic analysis (delta13C and delta15N) of Pygoscelis penguin chick tissues supports opportunistic sampling. AB - RATIONALE: Physiological stress and starvation have been shown to affect delta(13)C and delta(15)N isotope values and, given that animals often die from starvation, the cause of death may be an important factor to consider in stable isotope analyses of opportunistically collected samples. METHODS: We addressed this issue by comparing tissue stable isotope values of living and deceased Adelie (Pygoscelis adeliae) and Chinstrap Penguin (P. antarctica) chicks collected from the same respective populations. RESULTS: No significant difference was found between living and deceased penguin chick feather, down, and toenail isotope values and both groups displayed similar isotopic trends between tissue types. In addition, similar relationships were observed between both species and across several seasons. Furthermore, sub-dermal adiposity and cause of death (starvation and/or predation) had no significant effect on the delta(13)C and delta(15)N values. CONCLUSIONS: Our findings suggest that tissues from deceased penguins can be isotopically representative of tissues obtained from the living population, despite the cause of death, and support the use of opportunistic sampling in stable isotope analyses. PMID- 22302488 TI - The significance of ambient-temperature on pharmaceutical and endogenous compound abundance and distribution in tissues sections when analyzed by matrix-assisted laser desorption/ionization mass spectrometry imaging. AB - RATIONALE: Mass spectrometry imaging has proven to be a complementary assay to the traditional labeled-compound studies employed in drug research and development. However, there has been limited examination of the technical limitations of the technique with respect to small molecule stability in samples. METHODS: Raclopride dosed rat brain tissue sections (single dose i.v. 2 mg/kg) were allowed to warm to room temperature for 0 to 5 min prior to either a solvent based wet matrix-assisted laser desorption/ionization (MALDI) matrix or a solvent free dry MALDI matrix being applied. Subsequent MS imaging analysis was at a spatial resolution of 200 um, performed using a MALDI TOF/TOF (Ultraflex II, Bruker Daltonics). RESULTS: MALDI-MS has been used to monitor the time-dependent appearance and loss of small molecule abundance in tissue sections brought rapidly to room temperature for short periods of time. The abundances of a range of markers were seen to vary across the time course, both increasing and decreasing. The intensity of some markers changed significantly within 1 min. Importantly, the abundance of raclopride was seen to decrease over the 5-min time period examined. CONCLUSIONS: The results strongly indicate that considerable care is required to allow comparison of both pharmaceutical and endogenous compounds between MALDI-MSI experiments and also has implications for the standard practice of thaw-mounting multiple tissue sections onto MALDI-MS targets during MSI experiments. PMID- 22302489 TI - Comparison between a high-resolution single-stage Orbitrap and a triple quadrupole mass spectrometer for quantitative analyses of drugs. AB - The capabilities of a high-resolution (HR), accurate mass spectrometer (Exactive MS) operating in full scan MS mode was investigated for the quantitative LC/MS analysis of drugs in patients' plasma samples. A mass resolution of 50,000 (FWHM) at m/z 200 and a mass extracted window of 5 ppm around the theoretical m/z of each analyte were used to construct chromatograms for quantitation. The quantitative performance of the Exactive-MS was compared with that of a triple quadrupole mass spectrometer (TQ-MS), TSQ Quantum Discovery or Quantum Ultra, operating in the conventional selected reaction monitoring (SRM) mode. The study consisted of 17 therapeutic drugs including 8 antifungal agents (anidulafungin, caspofungin, fluconazole, itraconazole, hydroxyitraconazole posaconazole, voriconazole and voriconazole-N-oxide), 4 immunosuppressants (ciclosporine, everolimus, sirolimus and tacrolimus) and 5 protein kinase inhibitors (dasatinib, imatinib, nilotinib, sorafenib and sunitinib). The quantitative results obtained with HR-MS acquisition show comparable detection specificity, assay precision, accuracy, linearity and sensitivity to SRM acquisition. Importantly, HR-MS offers several benefits over TQ-MS technology: absence of SRM optimization, time saving when changing the analysis from one MS to another, more complete information of what is in the samples and easier troubleshooting. Our work demonstrates that U/HPLC coupled to Exactive HR-MS delivers comparable results to TQ-MS in routine quantitative drug analyses. Considering the advantages of HR-MS, these results suggest that, in the near future, there should be a shift in how routine quantitative analyses of small molecules, particularly for therapeutic drugs, are performed. PMID- 22302490 TI - Studying trophic interactions between a plant pathogen and two different antagonistic microorganisms using a 13C-labeled compound and isotope ratio mass spectrometry. AB - RATIONALE: The study of the interactions among microorganisms, especially between pathogens and other microorganisms, is a very useful way to identify possible biocontrol agents (BCAs). In this study we verified the capability of delta(13)C analysis using isotope ratio mass spectrometry (IRMS) to detect active parasitism or metabolic assimilation of (13)C-labeled Armillaria mellea (plant pathogen) by Trichoderma atroviride and Pseudomonas fluorescens (two BCAs). METHODS: The three microorganisms were labeled in pure-culture using a specific medium to which D glucose (13)C was added. The delta(13)C analysis of mycelia/cells and DNA was undertaken using IRMS at different times, to study the uptake kinetics of (13)C. The mechanisms of interaction were studied by implementing dual-culture tests and measuring the delta(13)C values of the two BCAs after 29 days of contact with the labeled pathogen. RESULTS: A. mellea absorbed (13)C more slowly (plateau at 21 days) than T. atroviride and P. fluorescens (3 and 1 day, respectively) in pure-culture. The maximum delta(13)C values were higher in A. mellea and T. atroviride mycelia (8,019.90/00 and 10,383.70/00, respectively) than in P. fluorescens (953.40/00 in cells). In dual-culture the mycelia of T. atroviride which remained in direct contact with labeled A. mellea showed an increased delta(13)C value with respect to the unlabeled treatment (66.40/00 and -26.60/00, respectively), due to active interaction. Lower assimilation of (13)C was detected in P. fluorescens. CONCLUSIONS: This work demonstrates that IRMS can be used for the in-depth study of direct parasitism and interaction process between biocontrol agents and labeled pathogens, allowing the screening of potential new BCAs. PMID- 22302491 TI - Using stable isotope analysis to discriminate gasoline on the basis of its origin. AB - RATIONALE: Leakage of gasoline and diesel from underground tanks has led to a severe environmental problem in many countries. Tracing the production origin of gasoline and diesel is required to enable the development of dispute resolution and appropriate remediation strategies for the oil-contaminated sites. METHODS: We investigated the bulk and compound-specific isotopic compositions of gasoline produced by four oil companies in South Korea: S-Oil, SK, GS and Hyundai. The relative abundance of several compounds in gasoline was determined by the peak height of the major ion (m/z 44). RESULTS: The delta(13)C(Bulk) and deltaD(Bulk) values of gasoline produced by S-Oil were significantly different from those of SK, GS and Hyundai. In particular, the compound-specific isotopic value (delta(13)C(CSIA)) of methyl tert-butyl ether (MTBE) in S-Oil gasoline was significantly lower than that of gasoline produced by other oil companies. The abundance of several compounds in gasoline, such as n-pentane, MTBE, n-hexane, toluene, ethylbenzene and o-xylene, differed widely among gasoline from different oil companies. CONCLUSIONS: This study shows that gasoline can be forensically discriminated according to the oil company responsible for its manufacture using stable isotope analysis combined with multivariate statistical analysis. PMID- 22302492 TI - Perfluorooctanoic acid and ammonium perfluorooctanoate: volatile surfactants for proteome analysis? AB - RATIONALE: Fluorinated surfactants are being explored as mass spectrometry (MS) friendly alternatives to sodium dodecyl sulfate (SDS) for proteome analysis. Previous work demonstrates perfluorooctanoic acid (PFOA) to be compatible with electrospray ionization (ESI)-MS. The high volatility of PFOA provides an intrinsic approach to potentially eliminate the surfactant during ESI, or alternatively through solvent evaporation prior to MS. The ammonium salt of PFOA, ammonium perfluorooctanoate (APFO), is likely favored for proteome experiments; the MS and liquid chromatography (LC)/MS tolerance of APFO has not been established for proteome applications. METHODS: Standard proteins and peptides, as well as a yeast proteome mixture, were individually spiked with surfactants (APFO, PFOA, SDS), and subjected to direct infusion ESI-MS, LC/MS/MS and LC/UV. The level of fluorinated surfactant remaining after solvent evaporation under varying conditions (time, pH, salt and protein content) was quantified and compared to the threshold tolerance level of the surfactant in an MS experiment (determined herein). RESULTS: Whereas PFOA is found ineffective at assisting protein solubilization, APFO is as effective as SDS for resolubilization of acetone-precipitated yeast proteins (~100% recovery). Unfortunately, the LC and MS threshold tolerance of APFO is only minimally greater than SDS (~2-fold higher concentration to cause 50% suppression). Nonetheless, the benefits of APFO in a proteome experiment are realized following a one-step evaporation protocol for removal of the surfactant in acidified solvent. CONCLUSIONS: APFO is considered a favoured alternative to SDS for proteome solubilization. Strictly speaking, APFO is not an 'MS-friendly' surfactant for proteome characterization; the detergent not only suppresses ESI signals at high concentration, but also perturbs reversed phase separation. However, the simplicity of APFO removal ahead of LC/MS justifies its use over the conventional SDS. PMID- 22302493 TI - Interactions of oligomers of organic polyethers with histidine amino acid. AB - RATIONALE: Knowledge on noncovalent intermolecular interactions of organic polyethers with amino acids is essential to gain a better understanding on how polymers assemble in organic nanoparticles which are promising for drug delivery and cryoprotection. The main objective of the present study was to determine how polyethers assemble around ionizable amino acids such as histidine. METHODS: Electrospray mass spectrometry was applied to probe the interactions in model systems consisting of polyethylene glycol PEG-400 or oxyethylated glycerol OEG-5 and amino acid histidine hydrochloride. Molecular dynamics simulation was utilized to visualize the structure of complexes of polyether oligomers with histidine in different charge states. RESULTS: Stable gas-phase clusters composed of polyether oligomers (PEG(n), OEG(n)) with protonated histidine- PEG(n)*His*H(+), OEG(n)*His*H(+), OEG(n)*OEG(m)*His*H(+) and chlorine counterion- PEG(n)*Cl(-), OEG(n)*Cl(-), were observed under electrospray conditions. Molecular dynamics simulation of representative polyether-histidine complexes revealed the stabilization of oligomers by multiple hydrogen and coordination bonds whereby charged groups are wrapped by the polymeric chains. CONCLUSIONS: The self-organization of polyether chains around the protonated imidazole group of histidine was revealed. This finding should be considered when modelling a pegylated protein structure and polyether-based organic nanoparticles. PMID- 22302494 TI - Using complementary mass spectrometric approaches for the determination of methylprednisolone metabolites in human urine. AB - RATIONALE: The metabolism of methylprednisolone is revisited in order to find new metabolites that could be important for distinguishing between different routes of administration. Recently developed liquid chromatography/tandem mass spectrometry (LC/MS/MS) strategies for the detection of corticosteroid metabolites have been applied to the study of methylprednisolone metabolism. METHODS: The structures of these metabolites were studied using two complementary mass spectrometric techniques: LC/MS/MS in product ion scan mode with electrospray ionization and gas chromatography/mass spectrometry (GC/MS) in full scan mode with electron ionization. Metabolites were also isolated by semipreparative liquid chromatography fractionation. Each fraction was divided into two aliquots; one was studied by LC/MS/MS and the other by GC/MS after methoxyamine-trimethylsilyl derivatization. RESULTS: The combination of all the structural information allowed us to propose a comprehensive picture of methylprednisolone metabolism in humans. Overall, 15 metabolites including five previously unreported compounds have been detected. Specifically, 16beta,17alpha,21-trihydroxy-6alpha-methylpregna-1,4-diene-3,11,20-trione, 17alpha,20beta,21-trihydroxy-6alpha-methylpregna-1,4-diene-3, 11-dione, 11beta,17alpha,21-trihydroxy-6alpha-hydroxymethylpregna-1,4-diene-3,20-dione, 11beta,17alpha,20xi,21-tetrahydroxy-6alpha-hydroxymethylpregna-1,4-diene-3-one, and 17alpha,21-dihydroxy-6alpha-hydroxymethylpregna-1,4-diene-3,11,20-trione are proposed as feasible structures for the novel metabolites. In addition to the expected biotransformations: reduction of the C20 carbonyl, oxidation of the C11 hydroxy group, and further 6beta-hydroxylation, we propose that hydroxylation of the 6alpha-methyl group can also take place. CONCLUSIONS: New metabolites have been identified in urine samples collected after oral administration of 40 mg of methylprednisolone. All identified metabolites were found in all samples collected up to 36 h after oral administration. However, after topical administration of 5 g of methylprednisolone aceponate, neither the parent compound nor any of the metabolites were detected. PMID- 22302495 TI - Improved accuracy in high-temperature conversion elemental analyzer delta18O measurements of nitrogen-rich organics. AB - RATIONALE: The use of high-temperature conversion (HTC) reduction systems interfaced with isotope ratio mass spectrometers for delta(18)O measurements of nitrogen-containing organic materials is complicated by isobaric interference from (14)N(16)O(+). This ion is produced in the ion source when N(2) reacts with trace oxygen shifting the m/z 30 baseline prior to elution of CO. METHODS: We compared adaptations to a typical HTC system (TC/EA) to determine the best method to measure the delta(18)O values of nitrogen-rich organic substrates including: (1) 0.6 and 1.5 m 5 A molecular sieve GC columns; (2) reduction of N(2) peak via He dilution; and (3) diversion of N(2) to waste via an automated four-port valve. These methods were applied to caffeine (IAEA-600), glycine, 4-nitroacetanilide, pentaerythritol tetranitrate (PETN) and cyclotrimethylene trinitramine (RDX), as well as pure and sodium azide-doped benzoic acid (IAEA-601) and sucrose (IAEA CH6). RESULTS: The efficiency of N(2) production in the HTC interface was highly variable among these compounds. Both the longer column and the dilutor improved, but did not eliminate, the adverse effects of nitrogen. CONCLUSIONS: The diversion of N(2) adequately addressed the nitrogen-induced problems as indicated by: (1) consistent m/z 30 background offset between reference and sample CO for both N-free and N-rich materials; (2) production of the highest delta(18)O values; and (3) high correlation between the increase in the delta(18)O values relative to the GC-only measurements and the N(2) peak area. Additional validation would require N-rich oxygen isotope standards for inter-laboratory comparisons. Further, more stringent methodology may improve the poor inter laboratory delta(18)O reproducibility of IAEA-600. PMID- 22302496 TI - Analysis of cipadesin limonoids from Cipadessa cinerascens using electrospray ionization quadrupole time-of-flight tandem mass spectrometry and quantum chemical calculations. AB - RATIONALE: Limonoids, a class of tetranortriterpenoids, exhibit various biological effects, such as insect antifeedant and growth regulating activities, antimicrobial activity, potent cell adhesion inhibitory effects, antimalarial activity, anticancer activities, and antioxidant activity. The potential application brings the need for reliable, fast and low-cost analysis of this class of compounds. METHODS: Six cipadesin limonoids (1-6), including a pairs of isomers, from leaves and barks of Cipadessa cinerascens were investigated by electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI QTOF-MS/MS) in positive-ion mode. Characteristic processes were further studied by theoretical calculations. RESULTS: 1,3-Hydrogen rearrangement might play a significant role in the cleavage of -O- bridge bond in ring B and further produces some characteristic ions. For [M + Na](+) precursor ions, the product ion at m/z 133 might indicate the structure of ring A and the losses of CO(2) and AcOH occur readily. Interestingly, the radical product ion at m/z 460 from [M + Na](+) ions seems to be the characteristic ion for compound 1. A deuterium labeling experiment supported the processes forming the radical ion. For [M + NH(4)](+) ions, high-abundance product ions resulting from sequential loss of AcOH can be observed. In addition, a pairs of isomers was unambiguously differentiated based on MS or MS/MS spectra. CONCLUSIONS: In summary, sufficient information obtained from fragmentation experiments of [M + Na](+), [M + NH(4)](+) or [M + H](+) precursor ions is especially valuable for rapid identification of these limonoids or their metabolites in complex mixtures. The high-abundance radical product ion is of scientific interest. PMID- 22302497 TI - Differentiation of two industrial oil sands process-affected waters by two dimensional gas chromatography/mass spectrometry of diamondoid acid profiles. AB - RATIONALE: Processing of the oil sands of Canada has produced large amounts of process-affected water (OSPW). Concerns have been raised over the possible environmental impacts of any leakage of OSPW from storage lagoons which contain toxicants, including organic acids. Natural weathering of oil sands deposits may also produce the toxicants, including the acids. Therefore, there is a need for differentiation of the possible natural and industrial sources of such toxicants and also for methods suitable for monitoring changes in the composition of OSPW during long-term storage. METHODS: Here we show in a simple preliminary study of the two samples currently available to us, by use of comprehensive two dimensional gas chromatography/time-of-flight mass spectrometry (GCxGC/ToF-MS), the distributions of methyl esters of individual isomeric diamondoid acids in OSPW from lagoons with different histories and from different industrial operators. RESULTS: We show that the distributions of methyl esters of individual isomeric diamondoid acids, including methyladamantane carboxylic and ethanoic acids, identified by comparison with data for reference compounds, can be differentiated readily. The use of acids with known structures, each verified by authentic acids, known toxicities and known and/or predictable physicochemical properties, to distinguish the different sources is advantageous, since factors likely to control the fate and dispersion of the acids can then more easily be predicted. It is postulated that the differences observed in the relative amounts of some of the acids result from variable extents of bacterial transformation of the organic matter in OSPW. CONCLUSIONS: The differences in distributions of diamondoid acids clearly vary between the two samples of OSPW and may prove very useful for monitoring the fate of different sources of OSPW both in storage and in the wider environment, once a wider collection of representative samples is available for study. PMID- 22302498 TI - Generation of negative ions from SF6 gas by means of hot surface ionization. AB - RATIONALE: Sulfur hexafluoride (SF(6)) is a man-made compound with many industrial applications. This compound is also one of the most powerful greenhouse gases with a relatively long atmospheric lifetime. Therefore, it is important to investigate processes leading to SF(6) decomposition. METHODS: A magnetic sector mass spectrometer with a thermoemission gaseous ion source was used in this study. The filament temperature was changed and monitored pyrometrically during the course of the studies. In the hot surface ionization process, negative ions may be generated both by free electron attachment to a molecule and by thermal dissociation followed by electron capture to the one of the fragments formed. RESULTS: Eight ion species: SF(5)(-), F(-), SF(6)(-), SF(4)(-), SF(3)(-), SF(2)(-), SF(-) and F(2)(-), with ion current intensities ratios of 1000:200:100:10:5:0.5:0.5:0.05, respectively, were detected. The filament temperature dependencies of the SF(5)(-), F(-), SF(6)(-), SF(4)(-) ion current intensities were measured. The optimal temperatures at which the maximum of the ion current intensity is observed were estimated in the 1830-2000 +/- 10 degrees C range. The formation of F(2)(-) ions is probably disturbed by a dissociation process at high temperatures. CONCLUSIONS: Negative surface ionization on the hot filament is a relatively simple and effective method for carrying out negative ion formation studies. Eight SF(6) decomposition channels leading to the formation of negative ions have been detected and analyzed using this technique. PMID- 22302499 TI - Human Biology Association archives at the Smithsonian Institution National Anthropological Archives. PMID- 22302500 TI - Molecular characterization and mRNA expression of grp78 and hsp90A in the estuarine copepod Eurytemora affinis. AB - The present study aimed to develop a method of quantification of heat shock protein transcript levels in the estuarine copepod Eurytemora affinis. For that, the full-length cDNA of the 78-kDa glucose-regulated protein (Ea-grp78) and the cytosolic 90-kDa heat shock protein (Ea-hsp90A) from this species have been cloned. These cDNA revealed, respectively, 2,370 and 2,299 bp with 1,971 and 2,124 bp open reading frames encoding 656 and 707 amino acids. Main features, sequence identities and phylogenetic analysis with other species were described. Then, the expression profiles were analysed using reverse transcription/real-time quantitative PCR method from copepods subjected to different thermic and osmotic stresses in laboratory, and from copepods directly sampled into the natural population of the Seine Estuary (France) along a salinity gradient. Thermic shock (7.5 degrees C, 22.5 degrees C and 30 degrees C during 90 min) significantly induced increases of transcript quantities ranged between 1.7- and 19.7-fold the levels observed in control conditions (15 degrees C). Hypo- and hyper-osmotic shocks (salinities of 1 and 30 during 90 min) caused a 2-fold induction of Ea hsp90A transcript level in comparison to controls (salinity of 15) whereas no significant change was measured for Ea-grp78. On the other hand, similar expression profiles were observed for the two transcripts after 72 h of exposition to salinities of 1 and 25 with a significant 2-fold induction observed for the lower salinity. To finish, strong expression inductions of both Ea-grp78 and Ea-hsp90A genes were observed in field copepods sampled at low salinity during the campaigns of June 2009 and May 2010. These results tend to show that the low salinity and the increase of temperature seem to have a synergic effect on stress condition of copepods. PMID- 22302501 TI - Dynamic contrast enhanced ultrasound assessment of the vascular effects of novel therapeutics in early stage trials. AB - Imaging is key in the accurate monitoring of response to cancer therapies targeting tumour vascularity to inhibit its growth and dissemination. Dynamic contrast enhanced ultrasound (DCE ultrasound) is a quantitative method with the advantage of being non-invasive, widely available, portable, cost effective, highly sensitive and reproducible using agents that are truly intravascular. Under the auspices of the initiative of the Experimental Cancer Medicine Centre Imaging Network, bringing together experts from the UK, Europe and North America for a 2-day workshop in May 2010, this consensus paper aims to provide guidance on the use of DCE ultrasound in the measurement of tumour vascular support in clinical trials. Key Points * DCE ultrasound can quantify and extract specific blood flow parameters, such as flow velocity, relative vascular volume and relative blood flow rate. * DCE ultrasound can be performed repeatedly and is therefore ideally suited for pharmacokinetic and pharmacodynamic studies evaluating vascular-targeted drugs. * DCE ultrasound provides a reproducible method of assessing the vascular effects of therapy in pre-clinical and early clinical trials, which is easily translatable into routine clinical practice. PMID- 22302502 TI - Chronic mesenteric ischaemia: 28-year experience of endovascular treatment. AB - OBJECTIVE: To report the outcomes associated with endovascular therapy for patients with chronic mesenteric ischemia (CMI). METHODS: A retrospective review of patients who underwent endovascular therapy for CMI between April 1981 and September 2009 at a single institution was performed. Procedural details, mesenteric arteries treated, technical and clinical success rates, outcomes per patient and per vessel were assessed. RESULTS: In 166 patients treatment was attempted using a variety of balloon and stent platforms during the 28-year period. The technical success rate was 97% per patient and 94% per vessel. The technical success rate of stenting (99.4%) was higher than for percutaneous transluminal angioplasty (PTA; 86%; P = 0.0001). Immediate clinical improvement was seen in 146 out of 166 (88.2%). The type of guidewire or device platform, brachial vs. femoral artery access, balloon and/or stent diameters used, and stenosis vs. occlusion had no statistical impact on mortality or the primary patency of any mesenteric artery outcomes. The outcome of the superior mesenteric artery (SMA) with PTA appears to be superior to that of stenting (P = 0.014). CONCLUSION: Technical success rates are improved with the use of stents; however, PTA use in the SMA seems to offer better primary patency rates. KEY POINTS: * Superior mesenteric artery (SMA) stenosis is often responsible for ischaemic symptoms. * Treatment with percutaneous transluminal angioplasty (PTA) seems superior to stenting * Although technical success rates are improved with the use of stents. * Higher mortality in the elderly and those presenting with nausea/vomiting/bloody stools. PMID- 22302503 TI - MR relaxometry of the liver: significant elevation of T1 relaxation time in patients with liver cirrhosis. AB - OBJECTIVES: To evaluate hepatic relaxation times T1, T2 and T2* in healthy subjects and patients with liver cirrhosis stratified by the Child-Pugh classification (CPC). METHODS: Sixty-one consecutive patients were stratified by CPC (class A026; B020; C015) and compared with age-matched controls (n = 31). Relaxometry measurements were performed at 1.5 T using six saturation recovery times (200-3,000 ms) to determine liver T1, six echo times (TE 14-113 ms) for T2 and eight TE (4.8-38 ms) for T2* assessment. Signal intensities in selected regions of interest in the liver parenchyma were fitted to theoretical models with least squares minimisation algorithms to determine T1, T2 and T2*. RESULTS: The most significant difference was the higher T1 values (852 +/- 132 ms) in cirrhotic livers compared with controls (678 +/- 45 ms, P < 0.0001). A less significant difference was seen for T2* (23 +/- 5 vs. 26 +/- 7 ms). Subdifferentiation showed a statistically significant difference between control group and individual CPC classes as well as between class C and classes A or B for T1 relaxation times. CONCLUSION: Measurement of T1 relaxation time can differentiate healthy subjects from patients with liver cirrhosis, and can distinguish between mild/moderate disease (CPC A/B) and advanced disease (CPC C). KEY POINTS: * Significantly elevated magnetic resonance T1 relaxation times are found in liver cirrhosis. * T1 relaxation times can distinguish healthy subjects from patients with liver cirrhosis. * T1 relaxation times can distinguish Child Pugh classes Aand B from C. PMID- 22302504 TI - Prevalence and stability of self-reported sexual orientation identity during young adulthood. AB - Based on date from Wave 3 and Wave 4 from National Longitudinal Survey of Adolescent Health (N=12,287), known as Add Health, the majority of young adults identified their sexual orientation as 100% heterosexual. The second largest identity group,''mostly heterosexual,''was larger than all other nonheterosexual identities combined. Comparing distributions across waves, which were approximately 6 years apart, stability of sexual orientation identity wasmore common than change. Stability was greatest among men and those identifying as heterosexual. Individuals who identified as 100% homosexual reported nearly the same level of stability as 100% heterosexuals. The bisexual categorywas themost unstable, with one quarter maintaining that status at Wave 4. Bisexual men who changed their identity distributed themselves among all other categories; among bisexual women, themost common shiftwas toward mostly heterosexual. Reflecting changes in identity, the proportion of heterosexuals decreased between the two waves. PMID- 22302505 TI - A mixed non-homogeneous hidden Markov model for categorical data, with application to alcohol consumption. AB - Hidden Markov models (HMMs) are frequently used to analyse longitudinal data, where the same set of subjects is repeatedly observed over time. In this context, several sources of heterogeneity may arise at individual and/or time level, which affect the hidden process, that is, the transition probabilities between the hidden states. In this paper, we propose the use of a finite mixture of non homogeneous HMMs (NH-HMMs) to face the heterogeneity problem. The non-homogeneity of the model allows us to take into account observed sources of heterogeneity by means of a proper set of covariates, time and/or individual dependent, explaining the variations in the transition probabilities. Moreover, we handle the unobserved sources of heterogeneity at the individual level, due to, for example, omitted covariates, by introducing a random term with a discrete distribution. The resulting model is a finite mixture of NH-HMM that can be used to classify individuals according to their dynamic behaviour or to estimate a mixed NH-HMM without any assumption regarding the distribution of the random term following the non-parametric maximum likelihood approach. We test the effectiveness of the proposal through a simulation study and an application to real data on alcohol abuse. PMID- 22302506 TI - Density functional study on the derivatives of purine. AB - The derivatives of purine are designed through substituting the hydrogen atoms on it for nitro and amino functional groups. Geometries and frequency are analyzed at the B3LYP/6-31 G** level of density functional theory(DFT). Heats of formation (HOF), bond dissociation energy(BDE) and detonation parameters (detonation velocity and detonation pressure) are obtained in detail at the same level. It is found that the BDE values of all derivatives are over 120KJ.mol(-1), and have high positive heats of formation. These derivatives possess excellent detonation properties, for B1, B2, and C, the detonation velocity are 9.58, 9.57,and 9.90 km.s(-1), and the detonation pressure are 43.40,46.05, and 46.37 Gpa, respectively, the detonation performances are better than cyclotrimethylenetrinitramine (RDX)and cyclotetramethylenetetranitramine (HMX). Hence, the derivations of purine may be promising well-behaved high energy density materials. PMID- 22302507 TI - Managing Perianal Crohn's Disease. AB - Perianal Crohn's Disease (CD) is a significant cause of morbidity in CD patients. Accurate identification of perianal involvement requires advanced imaging techniques in addition to physical exam. Treatment of the disease is aimed at improving both the perianal and intestinal manifestations. Proper treatment depends upon the severity of the disease and combines current medical and surgical therapies to maximize response. The ability to improve perianal disease has grown significantly since the introduction of anti-TNF agents which are now a mainstay of treatment along with antibiotics and immunomodulators. New experimental therapies are limited by lack of research to support their use. PMID- 22302508 TI - Have genomic discoveries in inflammatory bowel disease translated into clinical progress? AB - Inflammatory bowel disease (IBD) is a heterogeneous disease that can be challenging to diagnose and manage. As a result, significant efforts have been made in attempting to identify clinical, genomic, and serologic markers of disease that can aid in patient assessment and treatment. Recent genomic discoveries have the potential to change clinical practice by identifying those susceptible to IBD, predict natural history and guide choice of therapy. Panels of genetic and genomic markers are more likely to emerge as clinical tools, as opposed to individual allelic variants. Serology and biomarkers are already being used and guiding management but await integration with genomic panels before achieving their maximal potential. This article reviews the current state of IBD genetics and evolving molecular approaches that may have potential clinical impact. PMID- 22302509 TI - Promoting Task Accuracy and Independence in Students with Autism Across Educational Setting Through the Use of Individual Work Systems. AB - Strategies that promote the independent demonstration of skills across educational settings are critical for improving the accessibility of general education settings for students with ASD. This research assessed the impact of an individual work system on the accuracy of task completion and level of adult prompting across educational setting. Student accuracy and adult prompting were measured in both special and general education settings during academic work periods. Work systems, an element of structured teaching developed by Division TEACCH, are organized sets of visual information that inform a student about participation in work areas. A multiple-probe-across-participants design was used to evaluate the effects of the individual work systems. All participants demonstrated increased accuracy yet required less adult support across special and general education settings. Results were maintained when measured during a1 month follow-up probe. PMID- 22302510 TI - How to cheat when you cannot lie? Deceit pollination in Begonia gracilis. AB - Mimicry between rewarding and non-rewarding flowers within individuals has been accepted as a strategy favored by selection to deceive pollinators. It has been proposed that this mechanism relies on the exploitation of pollinator's sensory biases, but field evidence is still scarce. In this study, we describe the mechanism of deceit pollination in the monoecious herb Begonia gracilis, a species with exposed rewarding structures (pollen) and intersexual mimicry. Specifically, we test the role of mimicry and exploitation of sensory biases on the reproductive success of male (pollination visitation) and female flowers (probability of setting fruits). We show that pollinators' perception of the amount of reward provided by male flowers is influenced by the independent variation in the sizes of the androecium and the perianth. Large rewarding structures and small perianths were preferred by pollinators, suggesting a central role of the relative size of the rewarding structure on pollinators' foraging decisions. Hence, rewarding male flowers cheat pollinators by exploiting their sensory biases, a strategy followed by non-rewarding female flowers. We suggest that intersexual mimicry operates through the functional resemblance of male flowers' deceit strategy. Artificial manipulation of the flowers supports our findings in natural conditions. Overall, we propose that the continuous and independent variation in the size of the perianth and the reproductive organs among male and female flowers could itself be adaptive. PMID- 22302511 TI - Elevated CO2 differentially affects photosynthetic induction response in two Populus species with different stomatal behavior. AB - To understand dynamic photosynthetic characteristics in response to fluctuating light under a high CO(2) environment, we examined photosynthetic induction in two poplar genotypes from two species, Populus koreana 9 trichocarpa cv. Peace and Populus euramericana cv. I-55, respectively. Stomata of cv. Peace barely respond to changes in photosynthetic photon flux density (PFD), whereas those of cv. I-55 show a normal response to variations in PFD at ambient CO(2). The plants were grown under three CO2 regimes (380, 700, and 1,020 MUmol CO(2) mol(-1) in air) for approximately 2 months. CO2 gas exchange was measured in situ in the three CO2 regimes under a sudden PFD increase from 20 to 800 MUmol m(-2) s(-1). In both genotypes, plants grown under higher CO(2) conditions had a higher photosynthetic induction state, shorter induction time, and reduced induction limitation to photosynthetic carbon gain. Plants of cv. I-55 showed a much larger increase in induction state and decrease in induction time under high CO(2) regimes than did plants of cv. Peace. These showed that, throughout the whole induction process, genotype cv. I-55 had a much smaller reduction of leaf carbon gain under the two high CO(2) regimes than under the ambient CO(2) regime, while the high CO(2) effect was smaller in genotype cv. Peace. The results suggest that a high CO(2) environment can reduce both biochemical and stomatal limitations of leaf carbon gain during the photosynthetic induction process, and that a rapid stomatal response can further enhance the high CO(2) effect. PMID- 22302512 TI - Incorporating clonal growth form clarifies the role of plant height in response to nitrogen addition. AB - Nutrient addition to grasslands consistently causes species richness declines and productivity increases. Competition, particularly for light, is often assumed to produce this result. Using a long-term dataset from North American herbaceous plant communities, we tested whether height and clonal growth form together predict responses to fertilization because neither trait alone predicted species loss in a previous analysis. Species with a tall-runner growth form commonly increased in relative abundance in response to added nitrogen, while short species and those with a tall-clumped clonal growth form often decreased. The ability to increase in size via vegetative spread across space, while simultaneously occupying the canopy, conferred competitive advantage, although typically only the abundance of a single species within each height-clonal growth form significantly responded to fertilization in each experiment. Classifying species on the basis of two traits (height and clonal growth form) increases our ability to predict species responses to fertilization compared to either trait alone in predominantly herbaceous plant communities. Electronic supplementary material The online version of this article (doi:10.1007/s00442-012-2264-5) contains supplementary material, which is available to authorized users. PMID- 22302513 TI - Ontogenetic shifts in a prey's chemical defences influence feeding responses of a snake predator. AB - Foraging theory suggests that predator responses to potential prey should be influenced by prey chemical defences, but the effects of ontogenetic variation in such defences on prey vulnerability to predators remain unclear. Cane toads (Rhinella marina) are toxic to anurophagous snakes, including the keelback (Tropidonophis mairii, a natricine colubrid that occurs within the toads' invasive range in Australia). Toxin levels and diversity change through toad ontogeny, decreasing from the egg stage to metamorphosis, then increasing in postmetamorphic toads. If the toxin content of a prey item influences predator responses, we predict that keelbacks should exhibit selective predation on toads close to metamorphosis. The results of our laboratory trials on adult (field collected, and thus toad-experienced) and hatchling (laboratory-incubated, and thus toad-naive) keelbacks supported this prediction. The snakes selectively consumed later-stage rather than earlier-stage tadpoles, and earlier-stage rather than later-stage metamorphs. Our data are thus consistent with the hypothesis that ontogenetic changes in toxin content can affect individuals' vulnerability to predation. PMID- 22302514 TI - Foraging speed in staging flocks of semipalmated sandpipers: evidence for scramble competition. AB - Foraging speed is a key determinant of fitness affecting both foraging success and predator attack survival. In a scramble for food, for instance, evolutionary stable strategy models predict that speed should increase with competitor density and decrease when the risk of attack by predators increases. Foraging speed should also decrease in richer food patches where the level of competition is reduced. I tested these predictions in fall staging flocks of semipalmated sandpipers (Calidris pusilla) foraging for an evasive prey. Capture rate of these prey decreased with sandpiper density as the presence of competitors reduced the availability of resources for those behind. Foraging speed was evaluated indirectly by measuring the time needed to cross fixed boundaries on mudflats over 6 years. As predicted, foraging speed increased with sandpiper density and decreased with food density, but, unexpectedly, increased closer to obstructive cover where predation risk was deemed higher. When foraging closer to cover, from where predators launch surprise attacks, the increase in foraging speed may compensate for an increase in false alarms that interrupted foraging. While foraging in denser flocks decreases foraging success, joining such flocks may also increase safety against predators. In semipalmated sandpipers that occupy an intermediate position in the food chain, foraging behavior is influenced simultaneously by the evasive responses of their prey and by the risk of attack from their own predators. PMID- 22302515 TI - First reported case of interstitial 15 q15.3-q21.3 deletion diagnosed prenatally and characterized with array CGH in a fetus with an isolated short femur. AB - We report on a fetus with an isolated short femur detected by ultrasound and a de novo interstitial deletion of chromosome 15. The deletion was diagnosed prenatally by karyotype and further mapped by fluorescence in situ hybridization (FISH) and array comparative genomic hybridization (array-CGH) to bands 15q15.3 to 15q21.3 with a size of 11.11 Mb. Fetal autopsy showed characteristic minor anomalies, urinary abnormalities, and delayed bone maturation, but neither craniosynostosis, nor congenital heart defects as observed in previously reported cases. Despite the existence of ultrasound abnormalities, all five cases reported so far were diagnosed after birth. This is the first case of an interstitial deletion involving chromosomal band 15q15.3-q21.3 diagnosed prenatally and characterized at the molecular level. Our observation suggests the absence of imprinted genes in the area of 15q15-q22 and strengthens the hypothesis that a critical region for craniosynostosis may be mapped outside the deleted region in the present patient. PMID- 22302517 TI - Fifth Annual Huntington Disease Clinical Research Symposium. Organized by the Huntington Study Group. PMID- 22302516 TI - Reflective functioning in 70 patients suffering from bulimia nervosa. AB - OBJECTIVE: This study is the first to evaluate the reflective functioning abilities of patients suffering from bulimia nervosa (BN). METHOD: Seventy patients fulfilling Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for BN were interviewed with the Adult Attachment Interview, which was subsequently coded for reflective functioning (RF). RESULTS: On average, the sample of patients suffering from BN had close to normal mentalizing abilities. However, the distribution of RF scores was significantly different from the distribution of RF in a non-clinical control group, showing a more polarized pattern with more low and high RF scores. CONCLUSION: The study indicates that the theory of mentalization may contribute to understanding BN. However, bulimic pathology may develop and be maintained despite good mentalizing abilities. PMID- 22302518 TI - Total thyroidectomy with ultrasonic scalpel: a multicenter, randomized controlled trial. AB - BACKGROUND: The ultrasonic scalpel is a recently introduced device in head and neck surgery. Total thyroidectomy is the most common endocrine procedure performed by surgeons. METHODS: This was an open, phase IV, multicenter, randomized controlled trial (RCT) that compared the use of an ultrasonic scalpel with a conventional technique in patients who underwent total thyroidectomy. The outcomes were surgical complication rate, operative time, drainage volume, postoperative pain, and costs. RESULTS: In all, 261 patients were included in 11 centers. There was a mean difference of 17% of operative time in favor of the ultrasonic scalpel group. There were no differences in postoperative complications. There was a difference in costs of 14% in favor of the ultrasonic scalpel group, but it was not statistically significant. CONCLUSIONS: The use of an ultrasonic scalpel was as safe as that of the conventional technique and had the advantage of a shorter operative time and lower postoperative drainage. Costs were not different between groups. PMID- 22302519 TI - Early prediction of response to Vorinostat in an orthotopic rat glioma model. AB - Glioblastoma is the most common primary brain tumor and is uniformly fatal despite aggressive surgical and adjuvant therapy. As survival is short, it is critical to determine the value of therapy early on in treatment. Improved early predictive assessment would allow neuro-oncologists to personalize and adjust or change treatment sooner to maximize the use of efficacious therapy. During carcinogenesis, tumor suppressor genes can be silenced by aberrant histone deacetylation. This epigenetic modification has become an important target for tumor therapy. Suberoylanilide hydroxamic acid (SAHA, Vorinostat, Zolinza) is an orally active, potent inhibitor of histone deacetylase (HDAC) activity. A major shortcoming of the use of HDAC inhibitors in the treatment of patients with brain tumors is the lack of reliable biomarkers to predict and determine response. Histological evaluation may reflect tumor viability following treatment, but is an invasive procedure and impractical for glioblastoma. Another problem is that response to SAHA therapy is associated with tumor redifferentiation and cytostasis rather than tumor size reduction, thus limiting the use of traditional imaging methods. A noninvasive method to assess drug delivery and efficacy is needed. Here, we investigated whether changes in (1)H MRS metabolites could render reliable biomarkers for an early response to SAHA treatment in an orthotopic animal model for glioma. Untreated tumors exhibited significantly elevated alanine and lactate levels and reduced inositol, N-acetylaspartate and creatine levels, typical changes reported in glioblastoma relative to normal brain tissues. The (1)H MRS-detectable metabolites of SAHA-treated tumors were restored to those of normal-like brain tissues. In addition, reduced inositol and N-acetylaspartate were found to be potential biomarkers for mood alteration and depression, which may also be alleviated with SAHA treatment. Our study suggests that (1)H MRS can provide reliable metabolic biomarkers at the earliest stage of SAHA treatment to predict the therapeutic response. PMID- 22302520 TI - Identifying representative trees from ensembles. AB - Tree-based methods have become popular for analyzing complex data structures where the primary goal is risk stratification of patients. Ensemble techniques improve the accuracy in prediction and address the instability in a single tree by growing an ensemble of trees and aggregating. However, in the process, individual trees get lost. In this paper, we propose a methodology for identifying the most representative trees in an ensemble on the basis of several tree distance metrics. Although our focus is on binary outcomes, the methods are applicable to censored data as well. For any two trees, the distance metrics are chosen to (1) measure similarity of the covariates used to split the trees; (2) reflect similar clustering of patients in the terminal nodes of the trees; and (3) measure similarity in predictions from the two trees. Whereas the latter focuses on prediction, the first two metrics focus on the architectural similarity between two trees. The most representative trees in the ensemble are chosen on the basis of the average distance between a tree and all other trees in the ensemble. Out-of-bag estimate of error rate is obtained using neighborhoods of representative trees. Simulations and data examples show gains in predictive accuracy when averaging over such neighborhoods. We illustrate our methods using a dataset of kidney cancer treatment receipt (binary outcome) and a second dataset of breast cancer survival (censored outcome). PMID- 22302521 TI - Accurate prediction of glucuronidation of structurally diverse phenolics by human UGT1A9 using combined experimental and in silico approaches. AB - PURPOSE: Catalytic selectivity of human UGT1A9, an important membrane-bound enzyme catalyzing glucuronidation of xenobiotics, was determined experimentally using 145 phenolics and analyzed by 3D-QSAR methods. METHODS: Catalytic efficiency of UGT1A9 was determined by kinetic profiling. Quantitative structure activity relationships were analyzed using CoMFA and CoMSIA techniques. Molecular alignment of substrate structures was made by superimposing the glucuronidation site and its adjacent aromatic ring to achieve maximal steric overlap. For a substrate with multiple active glucuronidation sites, each site was considered a separate substrate. RESULTS: 3D-QSAR analyses produced statistically reliable models with good predictive power (CoMFA: q2 = 0.548, r2 = 0.949, r pred 2 = 0.775; CoMSIA: q2 = 0.579, r2 = 0.876, r pred 2 = 0.700). Contour coefficient maps were applied to elucidate structural features among substrates that are responsible for selectivity differences. Contour coefficient maps were overlaid in the catalytic pocket of a homology model of UGT1A9, enabling identification of the UGT1A9 catalytic pocket with a high degree of confidence. CONCLUSION: CoMFA/CoMSIA models can predict substrate selectivity and in vitro clearance of UGT1A9. Our findings also provide a possible molecular basis for understanding UGT1A9 functions and substrate selectivity. PMID- 22302522 TI - A nebulized gelatin nanoparticle-based CpG formulation is effective in immunotherapy of allergic horses. AB - PURPOSE: In the recent years, nanotechnology has boosted the development of potential drug delivery systems and material engineering on nanoscale basis in order to increase drug specificity and reduce side effects. A potential delivery system for immunostimulating agents such as cytosine-phosphate-guanine oligodeoxynucleotides (CpG-ODN) needs to be developed to maximize the efficacy of immunotherapy against hypersensitivity. In this study, an aerosol formulation of biodegradable, biocompatible and nontoxic gelatin nanoparticle-bound CpG-ODN 2216 was used to treat equine recurrent airway obstruction in a clinical study. METHODS: Bronchoalveolar lavage fluid was obtained from healthy and allergic horses to quantify Th1/Th2 cytokine levels before and after inhalation regimen. Full clinical examinations were performed to evaluate the therapeutic potential of this nebulized gelatin nanoparticle-based CpG formulation. RESULTS: Most remarkable was that regulatory anti-inflammatory and anti-allergic cytokine IL-10 expression was significantly triggered by five consecutive inhalations. Thorough assessment of clinical parameters following nanoparticle treatment indicated a partial remission of the allergic condition. CONCLUSION: Thus this study, for the first time, showed effectiveness of colloidal nanocarrier-mediated immunotherapy in food-producing animals with potential future applicability to other species including humans. PMID- 22302523 TI - Hepatocellular necrosis, fibrosis and microsomal activity determine the hepatic pharmacokinetics of basic drugs in right-heart-failure-induced liver damage. AB - PURPOSE: To explore how liver damage arising from cardio-hepatic syndromes in RHF affect the hepatic pharmacokinetics of basic drugs. METHODS: The hepatic pharmacokinetics of five selected basic drugs with different physicochemical properties were studied in IPRL from control rats and rats with RHF. Hepatic pharmacokinetic modelling was performed with a two-phase physiologically-based organ pharmacokinetic model with the vascular space and dispersion evaluated with the MID technique. The liver damage arising from RHF was assessed by changes in liver biochemistry and histopathology. The expression of various CYP isoforms was evaluated by real-time RT-PCR analysis. RESULTS: Four of the five basic drugs had a significantly lower E in RHF rat livers compared to the control rat livers. Hepatic pharmacokinetic analysis showed that both the CL int and PS were significantly decreased in the RHF rat livers. Stepwise regression analysis showed that the alterations in the pharmacokinetic parameters (E, CL int and PS) can be correlated to the observed histopathological changes (NI, CYP concentration and FI) as well as to the lipophilicity of the basic drugs (logP app). CONCLUSIONS: Serious hepatocellular necrosis and fibrosis induced by RHF affects both hepatic microsomal activity and hepatocyte wall permeability, leading to significant impairment in the hepatic pharmacokinetics of basic drugs. PMID- 22302526 TI - Vibration detection and discrimination in the masked birch caterpillar (Drepana arcuata). AB - Leaf-borne vibrations are potentially important to caterpillars for communication and risk assessment. Yet, little is known about the vibratory environment of caterpillars, or how they detect and discriminate between vibrations from relevant and non-relevant sources. We measured the vibratory 'landscape' of the territorial masked birch caterpillar Drepana arcuata (Drepanidae), and assessed its ability to detect and respond to vibrations generated by conspecific and predatory intruders, wind and rain. Residents of leaf shelters were shown to respond to low amplitude vibrations generated by a crawling conspecific intruder, since removal of the vibrations through leaf incision prevented the resident's response. Residents did not respond to large amplitude, low frequency disturbances caused by wind and rain alone, but did respond to approaching conspecifics under windy conditions, indicating an ability to discriminate between these sources. Residents also responded differently in the presence of vibrations generated by approaching predators (Podisus) and conspecifics. An analysis of vibration characteristics suggests that despite significant overlap between vibrations from different sources, there are differences in frequency and amplitude characteristics that caterpillars may use to discriminate between sources. Caterpillars live in a vibration-rich environment that we argue forms a prominent part of the sensory world of substrate bound holometabolous larvae. PMID- 22302527 TI - Computerized detection of lung nodules by CT for radiologic technologists in preliminary screening. AB - In Japan, radiologists and radiologic technologists are endeavoring to improve the quality of lung CT screening. In particular, preliminary screening by radiologic technologists is expected to decrease radiologists' burden and improve the accuracy of CT screening. We considered that an application of computer-aided detection (CAD) would also be as useful in preliminary screening as in the radiologist's regular reading. Our purpose in this study was to investigate the potential of the application of CAD to preliminary screening. CAD software that we developed was applied to 17 lung CT scans that radiologic technologists had pre-interpreted. A radiologist recognized 29 lung nodules from the CT images, whereas radiologic technologists did not recognize 11 of the 29 nodules at their pre-reading. Our CAD software detected lung nodules at an accuracy of 100% (29/29), with 4.1 false positives per case. The 11 nodules that radiologic technologists did not recognize were included in the CAD-detected nodules. This result suggests that the application of CAD may aid radiologic technologists in their preliminary screening. PMID- 22302528 TI - Bulimic behaviors and alcohol use: shared genetic influences. AB - Bulimic behaviors are frequently associated with alcohol use disorders. However, extant family and twin study findings have been inconsistent with regard to whether these behaviors share etiologic influences. A sample of 292 young adult, female twins was used to examine genetic and environmental factors underlying the association between binge eating and compensatory behaviors (e.g., vomiting)and alcohol use. Binge eating and compensatory behaviors were assessed using the Minnesota Eating Behavior Survey.Alcohol use was measured using the Alcohol Use Disorders Identification Test. Univariate models indicated that the heritability of binge eating, compensatory behaviors, and alcohol use was 41, 28, and 78%, respectively, with the remaining variance due to nonshared environmental effects.Bivariate models indicated that there was a moderate-to-large degree of overlap (genetic correlation = 0.31-0.61) in additive genetic factors between alcohol use and binge eating and compensatory behaviors, and no overlap in environmental effects. Findings suggest that these phenotypes co-aggregate in families and that similar genes or heritable traits may be contributing to their co-occurrence. PMID- 22302529 TI - Genetic influences on four measures of executive functions and their covariation with general cognitive ability: the Older Australian Twins Study. AB - "Executive functions" (EF) is a multidimensional construct which encompasses many higher-order cognitive control operations, and is considered a potential mediator of age-associated changes in other cognitive domains. Here we examine the heritability of four measures of EF, and the genetic influences on their covariation with general cognitive abilities (GCA) from the Older Australian Twins Study. Participants included 117 pairs of monozygotic twins, 98 pairs of dizygotic twins, and 42 single twins, with a mean age of 71. Genetic modeling showed that additive genetic factors contributed to 59, 63,29, and 31% of the variance in the four measures: working memory, verbal fluency, response inhibition and cognitive flexibility, respectively. The phenotypic associations among the four EF measures were modest, which is in line with other evidence that EF is a multi-dimensional construct.All of the covariation between the EF measures was attributable to a common genetic factor. Similarly, all of the covariation between EF and General Cognitive Ability was explained by a common genetic factor, with no significant covariance due to environmental (E) factors. The genetic correlations between the measures were moderately high, suggesting that they may have common biological underpinnings. The genetic influence in the covariation of the EF measures and GCA also suggests that some aspects of EF and GCA share the same genes or same set of genes. PMID- 22302530 TI - Vitamin E effect on controlled ovarian stimulation of unexplained infertile women. AB - PURPOSE: To determine Vit E effect on the treatment outcomes of women with unexplained infertility undergoing controlled ovarian stimulation and intrauterine insemination (IUI). METHODS: The study group (Group A, n053) underwent controlled ovarian stimulation with clomiphene citrate with Vit E administration, 400 IU/day p.o. while the control group(Group B, n050) underwent ovulation induction without VitE. Treatment outcomes were compared between the groups. RESULTS: There were no significant differences between the two groups with respect to the demographic outcomes. The difference in endometrial thickness on the day of hCG administration was significant between the two groups (p00.001).The effect of receiving Vit E on the implantation and the on going pregnancy rates were assesed Odds Ratio (OR) and corresponding 95% Confidence Intervals (CI). Receiving Vit E was not significantly associated with the implantation and the ongoing pregnancy rates; OR 0 1.22, 95% CI (0.44-3.4)and OR 0 1.43, 95% CI (0.49-4.1), respectively. CONCLUSION: Vit E administration may improve the endometrial response in unexplained infertile women via the likely antioxidant and the anticoagulant effects. It may also modulate the antiestrogenic effect of clomiphene citrate and the problem of a thin endometrium in these cycles may beadjusted PMID- 22302532 TI - Endoscopic laser fragmentation and removal of a nonremovable metal esophageal stent for persistent dysphagia: a technical note. AB - BACKGROUND: Self-expanding metal stents are widely used in the palliation of esophageal diseases (Todd, N Engl J Med 344(22):1681-1687, 2001). The majority are inserted for end-stage malignancy and are not designed to be removed. METHODS: We report the first recorded successful endoscopic removal of an "irremovable" stent by laser fragmentation after its placement became redundant. A 72-year-old man who had persistent dysphagia after esophageal stent insertion for Boerhaave's syndrome had his stent removed by Nd-YAG laser fragmentation at staged endoscopies. RESULTS: The stent was removed in its entirety and the patients' symptoms resolved. CONCLUSIONS: We describe a successful technique for the removal of a nonretrievable stent using laser fracture and endoscopic retrieval. This method of stent removal has not been previously reported. PMID- 22302531 TI - The link between the renin-angiotensin-aldosterone system and renal injury in obesity and the metabolic syndrome. AB - Obesity is a risk factor for type 2 diabetes mellitus (DM) and is associated with chronic kidney disease. Activation of the renin-angiotensin-aldosterone system (RAAS) is common in obesity. The RAAS is an important mediator of hypertension. Mechanisms involved in activation of the RAAS in obesity include sympathetic stimulation, synthesis of adipokines in the RAAS by visceral fat, and hemodynamic alterations. The RAAS is known for its role in regulating blood pressure and fluid and electrolyte homeostasis. The role of local/tissue RAAS in specific tissues has been a focus of research. Urinary angiotensinogen (UAGT) provides a specific index of the intrarenal RAAS. Investigators have demonstrated that sex steroids can modulate the expression and activity of the different components of the intrarenal RAAS and other tissues. Our data suggest that obese women without DM and hypertension have significantly higher levels of UAGT than their male counterparts. These differences existed without any background difference in the ratio of microalbumin to creatinine in the urine or the estimated glomerular filtration rate, raising a question about the importance of baseline gender differences in the endogenous RAAS in the clinical spectrum of cardiovascular diseases and the potential utility of UAGT as a marker of the intrarenal RAAS. Animal studies have demonstrated that modifying the amount of angiotensin, the biologically active component of the RAAS, directly influences body weight and adiposity. This article reviews the role of the RAAS in renal injury seen in obesity and the metabolic syndrome. PMID- 22302533 TI - Randomized controlled trial of laparoscopic gastric ischemic conditioning prior to minimally invasive esophagectomy, the LOGIC trial. AB - INTRODUCTION: Minimally invasive esophagectomy (MIE) is a viable alternative to open resection for the management of esophagogastric cancer. However, the technique may relate to a higher incidence of ischemia-related gastric conduit complications. Laparoscopic ischemic conditioning (LIC) by ligating the left gastric vessels 2 weeks before MIE may have a protective role, possibly through an improvement of conduit perfusion. This project was designed to evaluate whether LIC influenced ultimate conduit perfusion. METHODS: A randomized controlled trial was designed to compare MIE with LIC (L) against MIE without (N). The project began in May 2009 and was offered to consecutive patients with the objective of recruiting 22 in each arm. Sample size calculations were based on data from previous clinical series. The main outcome measure was perfusion recorded by validated laser Doppler fluximetry, at the fundus (F) and greater curve (G); performed at routine staging laparoscopy and every stage of an MIE. A perfusion coefficient measured as ratio at stage of MIE over baseline was used for statistical analysis. RESULTS: Sixteen patients were recruited before an interim analysis of the trial data. At staging laparoscopy perfusion at F was higher than at G (p = 0.016). In the L cohort, an apparent rise in perfusion at G is observed post intervention (p = 0.176). At MIE, baseline perfusion is comparable for both arms; however, a significant drop is observed at both locations once the stomach is mobilized and exteriorized (p = 0.001). Once delivered at the neck, perfusion coefficient is approximately 38% of baseline levels. However, there was no discernible difference between the L (38.3 +/- 12) and N (37.7 +/- 16.8) cohorts (p = 0.798). CONCLUSIONS: LIC does not translate into an improved perfusion of the gastric conduit tip. The benefits reported from published clinical series suggest that the resistance of the conduit to ischemia occurs through alternative possibly microcellular mechanisms. PMID- 22302534 TI - The use of novel hemostatic sealant (Tisseel) in laparoscopic myomectomy: a case control study. AB - BACKGROUND: This is the first case-control study on the use of a fibrin sealant (Tisseel) on uterine suture during laparoscopic myomectomy (LM), with the primary endpoint to evaluate the intraoperative bleeding and postoperative blood loss. In addition, we evaluated the time required to achieve hemostasis using Tisseel and how much it can influence operative time. METHODS: From December 2009 to January 2011, consecutive patients older than 18 years with symptomatic isolate intramural myoma with maximal diameter B6 cm and >= 4 cm and with a sonographically diagnosed free myometrium margin >= 0.5 cm were included in the study. We selected from our institute's database a group of consecutive patients with homogeneous features of the study group, who underwent laparoscopic myomectomy without Tisseel application. RESULTS: Fifteen women with symptomatic myoma were enrolled in the study (group A). Regarding the control group (group B), we selected a homogenous group of 15 patients with the same preoperative characteristics of the study group. Mean operative time was 47.7 min and 62.1 min, for groups A and B respectively (p < 0.05). Mean time required to achieve complete haemostasis was 195.5 s in group A and 361.8 in control group B (p < 0.0001). Mean estimated blood loss was 111.3 mL and 230 mL in groups A and B, respectively (p < 0.05). Mean hemoglobin decrease was 1.36 g/dL and 2.04 g/dL in groups A and B, respectively (p < 0.05). CONCLUSIONS: The use of Tisseel during LM may represent a valid alternative solution for obtaining hemostasis, reducing intra- and postoperative bleeding. Furthermore, it may help the surgeon to obtain a rapid healing of the injured surfaces, probably reducing the use of electrocoagulationand traumatisms. PMID- 22302535 TI - The optimal strategy for proximal mesh fixation during laparoscopic ventral rectopexy for rectal prolapse: an ex vivo study. AB - BACKGROUND: Laparoscopic ventral rectopexy (LVR) is an established technique for the treatment of rectal prolapse. Several techniques and devices can be used for proximal mesh fixation on the sacral promontory during this procedure. The aim of this study was to compare the fixation strength of a recently introduced screw for mesh fixation on the promontory during LVR with two other frequently used techniques. METHODS: An ex vivo experimental model using a porcine spinal column was designed to measure the strength of proximal mesh fixation. In a laparoscopic box trainer, a polypropylene mesh was anchored on the spinal column using three different fixation methods, i.e., the Protack 5-mm tacker device, Ethibond Excel 2-0 stitches, and the Karl Storz screw. Subsequently, increasing traction was applied to the mesh. This traction was applied at a standardized angle as determined by measuring the mean angle between the site of distal mesh fixation on the rectum and a line straight through the sacral promontory on 12 random dynamic MR scans of the pelvic floor after the LVR procedure. The applied force was measured at the moment that the fixation broke, using a calibrated electronic Newton meter. All fixation methods were tested ten times. RESULTS: The mean angle, as measured on the MR scans, was 100 degrees . The mean disruption force, which led to a break of the proximal mesh fixation, was 58 N for the three Protack tacks, 55 N for the two stitches, and 70 N for the new screw. The use of a screw therefore led to a significantly stronger fixation compared to the use of stitches (p <= 0.05). No significant difference was determined between the tacks and the screw fixation and between the tacks and the stitches fixation. CONCLUSION: The new screw for proximal mesh fixation during LVR procedures offers similar fixation strength when compared to tacks. The use of one screw for proximal mesh fixation is therefore a reasonable alternative to the use of several tacks or sutures. PMID- 22302536 TI - The burden of endoscopic retrograde cholangiopancreatography (ERCP) performed with the patient under conscious sedation. AB - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an invasive procedure that proves burdensome to patients. Nevertheless, very little data are available on patient tolerance of this procedure that may improve practice guidelines and could aid in decreasing the burden of ERCP. This study therefore investigated the burden of ERCP performed with the patient under conscious sedation. METHODS: Consecutive patients receiving ERCP under conscious sedation between November 2007 and December 2008 at the University Medical Center Utrecht and Erasmus MC Rotterdam (The Netherlands) were asked to participate in this study. The patients completed questionnaires on demographics, medical history, burden of ERCP (mental health, discomfort, and pain), symptoms and the EuroQol-5D (EQ-5D), including the EQ-VAS (lower EQ-5D scores and higher EQ-VAS scores represent a better quality of life). The paired t-test, the Kruskal-Wallis test, Pearson correlation, and logistic regression were used to evaluate the results. RESULTS: The questionnaire was returned by 149 (54%) of 276 eligible patients, 139 of whom completed the entire questionnaire (54% males; mean age, 60 +/- 14 years). Throat ache (p < 0.001) was the only symptom higher than baseline value 1 day after the ERCP. On day 1, about one-tenth of the patients experienced moderate to severe mental health problems, which were associated with a higher EQ 5D score before ERCP (p = 0.01). Slightly fewer than half of the patients experienced pain and discomfort during and immediately after ERCP. More discomfort was experienced by patients who underwent therapeutic ERCP (p < 0.05) and those with a higher EQ-5D score (p < 0.001) or lower VAS (p < 0.01). Pain was associated with younger age (p < 0.01), higher EQ-5D score (p < 0.001), and lower VAS (p < 0.01). CONCLUSION: One-third to one-half of patients experience pain and discomfort during and immediately after ERCP when it is performed with conscious sedation for the patient. Other sedation strategies, such as the use of general anesthesia or propofol, may well reduce the burden of ERCP, particularly for patients with a higher EQ-5D score, younger age, or therapeutic ERCP treatment. However, randomized trials are warranted. PMID- 22302537 TI - Comparable early changes in gastrointestinal hormones after sleeve gastrectomy and Roux-En-Y gastric bypass surgery for morbidly obese type 2 diabetic subjects. AB - BACKGROUND: Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGBP) are associated with similar type 2 diabetes mellitus (T2DM) resolution rates for morbidly obese subjects. However, the mechanisms underlying the resolution of T2DM after SG have not been clarified to date. This study aimed to compare the early changes in gastrointestinal hormones involved in insulin and glucagon secretion in morbidly obese T2DM subjects undergoing SG or RYGBP. METHODS: This prospective study investigated 12 subjects with T2DM who had undergone SG (n = 6) or RYGBP (n = 6). Five body mass index (BMI)-matched obese non-diabetic subjects and five BMI-matched obese diabetic subjects served as control subjects. Glucose, insulin, glucagon, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and GLP-2 were determined after a standardized mixed liquid meal before surgery and 6 weeks afterward. RESULTS: After 6 weeks, five of the six subjects in each surgical group presented with T2DM remission, although the area under the curve (AUC)0-120 of glucose was greater than that of the non-diabetic control subjects (P < 0.01). Postsurgically, the indices of insulin and glucagon secretion were comparable between the two surgical groups. The AUC0-120 of GLP-1 (P < 0.05) and GLP-2 (P < 0.05) was significantly and comparably enlarged after SG and RYGB. The postsurgical GIP response was significantly associated with the glucagon response throughout the meal test (rho = 0.747; P < 0.01). CONCLUSIONS: The data show that in a cohort of morbidly obese T2DM subjects, SG and RYGBP are associated with an early improvement in glucose tolerance, similar changes in insulin and glucagon secretion, and a similar GLP 1, GIP, and GLP-2 response to a standardized mixed liquid meal. PMID- 22302538 TI - A meningioma with peripheral rim enhancement on MRI. AB - Meningiomas are common, typically benign intracranial neoplasms with well demarcated borders.Meningiomas with indistinct boundaries have been reported.These can invade surrounding structures, and present surgical and diagnostic challenges. We present the case of an unusual meningioma in a 53-year old male in which preoperative magnetic resonance imaging (MRI) revealed an irregular lesion with clear boundaries and peripheral rim enhancement. Intraoperatively, however, no cleavage plane was apparent. Histological examination showed an increase of fibroconnective tissue with proliferation of dilated vessels in the periphery of the tumor concordant with the rim.Immunohistochemical staining of the tumor was positive for EMA and CD34, but negative for CEA, Ki67, and GFAP. Immunohistochemical staining of proliferating vessels in the periphery of the tumor was positive for CD34. A so-called 'capsule' structure was suggested according to MRI findings and pathological examination.The tumor was diagnosed as a mixed type meningioma,WHO grade I. PMID- 22302539 TI - Characterization of a novel KRAS mutation identified in Noonan syndrome. AB - Noonan syndrome (NS) is the most common non-chromosomal syndrome seen in children and is characterized by short stature, dysmorphic facial features, chest deformity, a wide range of congenital heart defects and developmental delay of variable degree. Mutations in the Ras/mitogen-activated protein kinase (MAPK) signaling pathways cause about 70% of NS cases with a KRAS mutation present in about 2%. In a cohort of 65 clinically confirmed NS patients of Japanese origin, we screened for mutations in the RAS genes by direct sequencing. We found a novel mutation in KRAS with an amino acid substitution of asparagine to serine at codon 116 (N116S). We analyzed the biological activity of this mutant by ectopic expression of wild-type or mutant KRAS. NS-associated KRAS mutation resulted in Erk activation and active Ras-GTP levels, and exhibited mild cell proliferation. In addition, kras-targeted morpholino knocked-down zebrafish embryos caused heart and craniofacial malformations, while the expression of mutated kras resulted in maldevelopment of the heart. Our findings implicate that N116S change in KRAS is a hyperactive mutation which is a causative agent of NS through maldevelopment of the heart. PMID- 22302540 TI - Self-powered microscale pumps based on analyte-initiated depolymerization reactions. PMID- 22302541 TI - Concurrent administration of atypical antipsychotics and donepezil: drug interaction study in rats. AB - Psychotic and behavioral symptoms are common in patients with dementia. Thus, it is rational to assume that patients with dementia would gain benefit from combination therapy of an antipsychotic agent and a cognitive enhancer. Antipsychotics are not approved by the US FDA in elderly patients with dementia but their use is still prevalent in other population. In the current study, we investigate the effect of atypical antipsychotics on acetylcholine modulation by donepezil. In addition, the plasma pharmacokinetics on concurrent administration of these drugs was studied. Acetylcholine modulation was carried out in the ventral hippocampus of Sprague-Dawley rats using brain microdialysis technique. In a parallel group of animals, pharmacokinetic parameters were evaluated on administration of donepezil (5.0 mg kg(-1), ip) alone and in combination with olanzapine, clozapine, or quetiapine. Donepezil produced 348% increase in hippocampal acetylcholine levels. Coadministration of olanzapine and donepezil produced 393% increase in extracellular acetylcholine, and the effect was supported by a significantly (p < 0.05) decreased clearance of donepezil in plasma. Whereas, other plasma pharmacokinetic parameters of donepezil "AUC(0 24h), T (1/2) and T (max)" were moderately altered after this combination treatment. Concurrent administrations of clozapine or quetiapine with donepezil produced a non-significant change in acetylcholine levels in comparison to donepezil alone. The plasma pharmacokinetics of donepezil was unaltered. Results from this preclinical investigation indicate that extrapyramidal side effects may precipitate upon coadministration of donepezil with olanzapine. Care must be exercised by physicians and caregivers while administering these two drugs together. PMID- 22302542 TI - Superficial temporal artery aneurysm: Diagnosis and treatment options. AB - BACKGROUND: Superficial temporal artery (STA) aneurysms are an uncommon entity and mostly described in case studies. The purpose of this review was to show the studied clinical presentation, diagnostic modalities, and treatment modalities of STA aneurysms. METHODS: A review was performed of reports on STA aneurysms published until December 2010, using the MEDLINE and Cochrane databases. RESULTS: One hundred sixty-six pseudoaneurysms and 20 true aneurysms were described. The majority of patients presented with a painless pulsatile mass. Historically, angiography was most often used, but ultrasound scan, CT, and MRI may be superior. Surgical resection was performed in 128 pseudoaneurysms and 20 true aneurysms with 1 recurrence and few complications. Endovascular approaches were used in 13% of pseudoaneurysms with an 80% success rate. CONCLUSION: Pseudoaneurysms are mostly the result of blunt trauma as opposed to true aneurysms which usually occur spontaneously. Surgical resection is a safe treatment modality, but endovascular treatment might be considered in a selected group of patients. (c) 2012 Wiley Periodicals, Inc. Head Neck, 2013. PMID- 22302543 TI - Serologic diagnosis of NMO: a multicenter comparison of aquaporin-4-IgG assays. AB - OBJECTIVES: Neuromyelitis optica (NMO) immunoglobulin G (IgG) (aquaporin-4 [AQP4] IgG) is highly specific for NMO and related disorders, and autoantibody detection has become an essential investigation in patients with demyelinating disease. However, although different techniques are now used, no multicenter comparisons have been performed. This study compares the sensitivity and specificity of different assays, including an in-house flow cytometric assay and 2 commercial assays (ELISA and transfected cell-based assay [CBA]). METHODS: Six assay methods (in-house or commercial) were performed in 2 international centers using coded serum from patients with NMO (35 patients), NMO spectrum disorders (25 patients), relapsing-remitting multiple sclerosis (39 patients), miscellaneous autoimmune diseases (25 patients), and healthy subjects (22 subjects). RESULTS: The highest sensitivities were yielded by assays detecting IgG binding to cells expressing recombinant AQP4 with quantitative flow cytometry (77; 46 of 60) or visual observation (CBA, 73%; 44 of 60). The fluorescence immunoprecipitation assay and tissue-based immunofluorescence assay were least sensitive (48%-53%). The CBA and ELISA commercial assays (100% specific) yielded sensitivities of 68% (41 of 60) and 60% (36 of 60), respectively, and sensitivity of 72% (43 of 60) when used in combination. CONCLUSIONS: The greater sensitivity and excellent specificity of second-generation recombinant antigen-based assays for detection of NMO-IgG in a clinical setting should enable earlier diagnosis of NMO spectrum disorders and prompt initiation of disease-appropriate therapies. PMID- 22302544 TI - The next step in understanding the prognosis of cerebral cavernous malformations. PMID- 22302545 TI - Natalizumab-associated PML identified in the presymptomatic phase using MRI surveillance. PMID- 22302546 TI - Fatal PML associated with efalizumab therapy: insights into integrin alphaLbeta2 in JC virus control. AB - OBJECTIVES: Progressive multifocal leukoencephalopathy (PML) has become much more common with monoclonal antibody treatment for multiple sclerosis and other immune mediated disorders. METHODS: We report 2 patients with severe psoriasis and fatal PML treated for >=3 years with efalizumab, a neutralizing antibody to alphaLbeta2 leukointegrin (LFA-1). In one patient, we conducted serial studies of peripheral blood and CSF including analyses of leukocyte phenotypes, migration ex vivo, and CDR3 spectratypes with controls coming from HIV-infected patients with PML. Extensive pathologic and histologic analysis was done on autopsy CNS tissue of both patients. RESULTS: Both patients developed progressive cognitive and motor deficits, and JC virus was identified in CSF. Despite treatment including plasma exchange (PE) and signs of immune reconstitution, both died of PML 2 and 6 months after disease onset. Neuropathologic examination confirmed PML. Efalizumab treatment was associated with reduced transendothelial migration by peripheral T cells in vitro. As expression levels of LFA-1 on peripheral T cells gradually rose after PE, in vitro migration increased. Peripheral and CSF T-cell spectratyping showed CD8+ T-cell clonal expansion but blunted activation, which was restored after PE. CONCLUSIONS: From these data we propose that inhibition of peripheral and intrathecal T-cell activation and suppression of CNS effector phase migration both characterize efalizumab-associated PML. LFA-1 may be a crucial factor in homeostatic JC virus control. PMID- 22302547 TI - Understanding epileptogenesis in calcified neurocysticercosis with perfusion MRI. AB - OBJECTIVES: Calcified cysticercus larva with perilesional abnormality is thought to be responsible for seizures in patients with neurocysticercosis (NCC). However, it is not well understood why some calcified cysts are associated with seizures even without perilesional abnormality. METHODS: The study group consists of 30 subjects from an ongoing survey for disease burden estimation of a swine farming community who had a single calcified lesion without any perilesional abnormality with or without presentation of seizures. Each group consisted of 15 patients with calcified cysts and was labeled as asymptomatic and symptomatic. We performed dynamic contrast-enhanced (DCE) MRI on all these subjects and determined serum matrix metalloproteinase-9 (MMP-9) levels and MMP-9 gene polymorphisms. RESULTS: DCE-MRI-derived rate transfer constant (k(ep)) and serum MMP-9 levels showed significant differences between symptomatic and asymptomatic subjects. We observed an increase in the MMP-9 levels, k(ep), and the volume transfer coefficient (k(trans)) in these lesions. We also observed a significant increase in MMP-9 (R279Q) gene polymorphism in symptomatic subjects compared with asymptomatic and control subjects. CONCLUSIONS: Perilesional inflammation, which varies from symptomatic to asymptomatic subjects, can be quantified using DCE-MRI in calcified cysticercosis and may help distinguish these 2 groups with similar imaging findings. The observed increase in k(ep) with serum MMP-9 levels suggests that the former may serve as a biomarker of MMP-9 levels in these subjects. The significant MMP-9 (R279Q) gene polymorphism in symptomatic subjects might explain the differences in the observed DCE-MRI indices between symptomatic and asymptomatic subjects. PMID- 22302548 TI - Accelerated cortical atrophy in cognitively normal elderly with high beta-amyloid deposition. AB - OBJECTIVE: Given the recent and growing interest in the concepts of prodromal and presymptomatic Alzheimer disease, it is crucial to determine whether the presence of beta-amyloid (Abeta) in the brain of asymptomatic elderly individuals is a pathologic condition associated with accelerated neuronal and synaptic loss. The aim of the present study was to assess whether Abeta influences the rate of atrophy in cognitively normal elderly individuals. METHODS: Seventy-four healthy elderly individuals underwent an MRI scan and a 11C-Pittsburgh compound B (PiB) PET scan at baseline and a second MRI scan 18 months later. Voxel-wise analyses were performed using maps of annual rate of atrophy generated from the serial MRI scans, including comparison between individuals with high vs low neocortical PiB and correlation with baseline neocortical PiB. RESULTS: The rate of atrophy was significantly higher in the normal elderly individuals with high PiB compared with those with low PiB and was significantly correlated with baseline neocortical PiB, with the highest significance in the temporal neocortex and the posterior cingulate cortex. CONCLUSIONS: Our findings show that the presence of Abeta in the brain, known to occur in about one-third of asymptomatic elderly individuals, is actually a pathologic state associated with accelerated atrophy. They also suggest that therapy aimed to reduce the neurodegenerative process should be commenced in presymptomatic individuals with high PiB. PMID- 22302550 TI - beta-Amyloid burden in healthy aging: regional distribution and cognitive consequences. AB - OBJECTIVE: Several lines of evidence suggest that pathologic changes underlying Alzheimer disease (AD) begin years prior to the clinical expression of the disease, underscoring the need for studies of cognitively healthy adults to capture these early changes. The overall goal of the current study was to map the cortical distribution of beta-amyloid (Abeta) in a healthy adult lifespan sample (aged 30-89), and to assess the relationship between elevated amyloid and cognitive performance across multiple domains. METHODS: A total of 137 well screened and cognitively normal adults underwent Abeta PET imaging with radiotracer (18)F-florbetapir. Abeta load was estimated from 8 cortical regions. Participants were genotyped for APOE and tested for processing speed, working memory, fluid reasoning, episodic memory, and verbal ability. RESULTS: Abeta deposition is distributed differentially across the cortex and progresses at varying rates with age across cortical brain regions. A subset of cognitively normal adults aged 60 and over show markedly elevated deposition, and also had a higher rate of APOE epsilon4 (38%) than nonelevated adults (19%). Abeta burden was linked to poorer cognitive performance on measures of processing speed, working memory, and reasoning. CONCLUSIONS: Even in a highly selected lifespan sample of adults, Abeta deposition is apparent in some adults and is influenced by APOE status. Greater amyloid burden was related to deleterious effects on cognition, suggesting that subtle cognitive changes accrue as amyloid progresses. PMID- 22302551 TI - What causes seizures in patients with calcified neurocysticercal lesions? PMID- 22302552 TI - Levels of heparin-releasable TFPI are increased in first-ever lacunar stroke patients. AB - OBJECTIVES: New insights in the pathophysiology of lacunar stroke (LS) suggest that it is caused by increased permeability of the blood-brain barrier due to endothelial activation. Because endothelial cells are the major production and storage site of tissue factor pathway inhibitor (TFPI), this protein can be used as marker of endothelial activation. In this observational study we measured the different pools of TFPI, as a marker of endothelial function, in first-ever lacunar stroke patients. METHODS: We determined antigen levels of total and free full-length (FL) TFPI using ELISA in 149 patients and 42 controls. Heparin releasable free FL TFPI was determined in a random subset of 17 patients and 15 controls. By brain MRI, we classified LS patients as having isolated lacunar infarct (ILA) or silent ischemic lesions (SILs). RESULTS: Plasma levels of total TFPI were highest in patients with SILs compared with those with ILA, but this association disappeared after correction for age and levels of low-density lipoprotein cholesterol. However, levels of heparin-releasable free FL TFPI were higher in patients than in controls. CONCLUSIONS: Although ambient plasma levels of total TFPI were not different in subtypes of LS, the increased levels of heparin-releasable TFPI in patients suggest a role of endothelial activation in the pathogenesis of LS. PMID- 22302553 TI - Prospective hemorrhage risk of intracerebral cavernous malformations. AB - OBJECTIVE: Our goal was to describe the prospective risk and timing of symptomatic hemorrhage in a large cohort of followed patients with intracerebral cavernous malformations (ICMs). METHODS: All patients between 1989 and 1999 with the radiographic diagnosis of intracerebral cavernous malformation were identified retrospectively. The records and radiographic data were reviewed, and follow-up after diagnosis was obtained. An incidence rate was used to calculate annual risk of symptomatic hemorrhage. Predictive factors for outcomes used univariate and multivariable analysis with p < 0.05. RESULTS: A total of 292 patients were identified (47.3%male) with 2,035 patient years of follow-up. Seventy-four patients presented with hemorrhage, 108 with symptoms not related to hemorrhage (seizure or focal deficit), and 110 as asymptomatic. The overall annual rate of hemorrhage in those presenting initially with hemorrhage, with symptoms not related to hemorrhage, or as an incidental finding was 6.19%, 2.18%, and 0.33%, respectively. Patients who presented initially with symptomatic hemorrhage (hazard ratio 5.14; 95% confidence interval [CI] 2.54-10.4; p < 0.001) were at higher risk for future hemorrhage, and hemorrhage risk decreased with time. Male gender (hazard ratio 2.36; 95% CI 1.14-4.89; p = 0.02), and multiplicity of ICMs (hazard ratio 2.65; 95% CI 1.30-5.43; p = 0.01) also increased the risk of hemorrhage. The median time from first to second hemorrhage was 8 months. CONCLUSIONS: This study provides an estimate of prospective annual symptomatic hemorrhage risk in patients with ICMs stratified by initial presenting symptom. Prior hemorrhage, male gender, and multiplicity of ICMs may predict future hemorrhage. Hemorrhage risk decreases with time in those initially presenting with hemorrhage. PMID- 22302554 TI - Age and diagnostic performance of Alzheimer disease CSF biomarkers. AB - OBJECTIVES: Core CSF changes in Alzheimer disease (AD) are decreased amyloid beta(1-42), increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD type brain pathology in cognitively unaffected elderly. METHODS: We investigated effects of age on the diagnostic performance of CSF biomarkers in a uniquely large multicenter study population, including a cross-sectional cohort of 529 patients with AD dementia (median age 71, range 43-89 years) and 304 controls (67, 44-91 years), and a longitudinal cohort of 750 subjects without dementia with mild cognitive impairment (69, 43-89 years) followed for at least 2 years, or until dementia diagnosis. RESULTS: The specificities for subjects without AD and the areas under the receiver operating characteristics curves decreased with age. However, the positive predictive value for a combination of biomarkers remained stable, while the negative predictive value decreased only slightly in old subjects, as an effect of the high AD prevalence in older ages. CONCLUSION: Although the diagnostic accuracies for AD decreased with age, the predictive values for a combination of biomarkers remained essentially stable. The findings highlight biomarker variability across ages, but support the use of CSF biomarkers for AD even in older populations. PMID- 22302557 TI - Blood oxygen level dependent angiography (BOLDangio) and its potential applications in cancer research. AB - Clinically, development of anti-angiogenic drugs for cancer therapy is pivotal. Longitudinal monitoring of tumour angiogenesis can help clinicians determine the effectiveness of anti-angiogenic therapy. Blood oxygen level dependent (BOLD) effect has been widely used for functional imaging and tumour oxygenation assessment. In this study, the BOLD effect is investigated under different levels of oxygen inhalation for the development of a novel angiographic MRI technique, blood oxygen level dependent angiography (BOLDangio). Under short-term (<10 min) generalized hypoxia induced by inhalation of 8% oxygen, we measure BOLD contrast as high as 25% from vessels at 9.4T using a simple gradient echo (GRE) pulse sequence. This produces high-resolution 2D and 3D maps of normal and tumour brain vasculature in less than 10 minutes. Additionally, this technique reliably detects metastatic tumours and tumour-induced intracranial hemorrhage. BOLDangio provides a sensitive research tool for MRI of vasculature under normal and pathological conditions. Thus, it may be applied as a simple monitoring technique for measuring the effectiveness of anti-angiogenic drugs in a preclinical environment. PMID- 22302558 TI - Evaluation of exercise capacity using wave intensity in chronic heart failure with normal ejection fraction. AB - Impaired exercise capacity has been found in patients with diastolic dysfunction with preserved systolic function. Although conventional transthoracic echocardiography (TTE) provides useful clinical information about systolic and diastolic cardiac function, its capability to evaluate exercise capacity has been controversial. The inertia force of late systolic aortic flow is known to have a tight relationship with left ventricular (LV) performance during the period from near end-systole to isovolumic relaxation. The inertia force and the time constant of LV pressure decay during isovolumic relaxation can be estimated noninvasively using the second peak (W(2)) of wave intensity (WI), which is measured with an echo-Doppler system. We sought to determine whether W(2) is associated with exercise capacity in patients with chronic heart failure with normal ejection fraction (HFNEF) and to compare its ability to predict exercise capacity with parameters obtained by conventional TTE including tissue Doppler imaging. Sixteen consecutive patients with chronic HFNEF were enrolled in this study. Wave intensity was obtained with a color Doppler system for measurement of blood velocity combined with an echo-tracking system for detecting changes in vessel diameter. Concerning conventional TTE, we measured LV ejection fraction (EF), peak velocities of early (E) and late (A) mitral inflow using pulse-wave Doppler, and early (Ea) and late (Aa) diastolic velocities using tissue Doppler imaging. Left ventricular EF, E/A ratio, Ea, and E/Ea ratio did not correlate with exercise capacity, whereas W(2) significantly correlated with peak VO(2) (r = 0.54, p = 0.03), VE/VCO(2) slope (r = -0.53, p = 0.03), and DeltaVO(2)/DeltaWR (r = 0.56, p = 0.02). W(2) was associated with exercise capacity in patients with chronic HFNEF. In conclusion, W(2) is considered to be clinically more useful than conventional TTE indices for evaluating exercise capacity in patients with chronic HFNEF. PMID- 22302559 TI - A nonparametric test for equality of survival medians. AB - In clinical trials, researchers often encounter testing for equality of survival medians across study arms based on censored data. Even though Brookmeyer and Crowley introduced a method for comparing medians of several survival distributions, still some researchers misuse procedures that are designed for testing the homogeneity of survival curves. These procedures include the log rank, Wilcoxon, and Cox models. This practice leads to inflation of the probability of a type I error, particularly when the underlying assumptions of these procedures are not met. We propose a new nonparametric method for testing the equality of several survival medians based on the Kaplan-Meier estimation from randomly right-censored data. We derive asymptotic properties of this test statistic. Through simulations, we compute and compare the empirical probabilities of type I errors and the power of this new procedure with those of the Brookmeyer-Crowley, log-rank, and Wilcoxon methods. Our simulation results indicate that the performance of these test procedures depends on the level of censoring and appropriateness of the underlying assumptions. When the objective is to test homogeneity of survival medians rather than survival curves and the assumptions of these tests are not met, some of these procedures severely inflate the probability of a type I error. In these situations, our test statistic provides an alternative to the Brookmeyer-Crowley test. PMID- 22302560 TI - Gamma knife stereotactic radiosurgery for drug resistant or intolerant invasive prolactinomas. AB - We evaluated the efficacy of Gamma knife stereotactic radiosurgery (GKSR) as an adjunctive management modality for patients with drug resistant or intolerant cavernous sinus invasive prolactinomas. Twenty-two patients with cavernous sinus invasive prolactinoma underwent GKSR between 1994 and 2009. Thirteen patients were dopamine agonist (DA) resistant. Six patients were intolerant to DA. Three patients chose GKSR as their initial treatment modality in hopes they might avoid life long suppression medication. The median tumor volume was 3.0 cm3 (range 0.3 11.6). The marginal tumor dose (median= 15 Gy, range 12-25 Gy) prescribed was based on the dose delivered to the optic apparatus. The median follow-up interval was 36 months (range, 12-185). Endocrine normalization was defined as a normal serum prolactin level off DA (cure) or on DA. Endocrine improvement was defined asa decreased but still elevated serum prolactin level. Endocrine deterioration was defined as an increased serum prolactin level. Endocrine normalization was achieved in six(27.3%) patients. Twelve (54.5%) patients had endocrine improvement. Four patients (18.2%) developed delayed increased prolactin. Imaging defined local tumor control was achieved in 19 (86.4%) patients, 12 of whom had tumor regression. Three patients had a delayed tumor progression and required additional management. One patient developed a new pituitary axis deficiency after GKSR. Invasive prolactinomas continue to pose management challenges. GKSR is a non invasive adjunctive option that may reduce prolactin levels in patients who are resistant to or intolerant of suppression medication. In a minority of cases, patients may no longer require long term suppression therapy. PMID- 22302561 TI - Synergistic antibacterial efficacy of early combination treatment with tobramycin and quorum-sensing inhibitors against Pseudomonas aeruginosa in an intraperitoneal foreign-body infection mouse model. AB - OBJECTIVES: Quorum sensing (QS)-deficient Pseudomonas aeruginosa biofilms formed in vitro are more susceptible to tobramycin than QS-proficient P. aeruginosa biofilms, and combination treatment with a QS inhibitor (QSI) and tobramycin shows synergistic effects on the killing of in vitro biofilms. We extended these results to an in vivo P. aeruginosa foreign-body biofilm model. The effect of treatment initiated prophylactically was compared with treatment initiated 11 days post-insertion. METHODS: Silicone tube implants pre-colonized with wild-type P. aeruginosa were inserted into the peritoneal cavity of BALB/c mice. Mice were treated with intraperitoneal or subcutaneous injections of the QSIs furanone C 30, ajoene or horseradish juice extract in combination with tobramycin. Mice were euthanized on day 1, 2, 3 or 14 post-infection for the estimation of quantitative bacteriology, histopathology and cytokine measurements. RESULTS: Combination treatment of P. aeruginosa resulted in a significantly lower cfu per implant as compared with the placebo groups for all QSIs tested. For early-initiated treatment, a significant difference in clearing was also observed between the combination group and the single-treatment groups, and between the placebo group and the single-treatment groups. In one case a significant difference in clearing was found between the two single-treatment groups. CONCLUSIONS: Synergistic antimicrobial efficacy could be achieved when treating mice with both a QSI and tobramycin, resulting in an increased clearance of P. aeruginosa in a foreign body infection model. Our study highlights the important prospects in developing an early combinatory treatment strategy for chronic infections. PMID- 22302562 TI - Trends of transmitted drug resistance of HIV-1 and its impact on treatment response to first-line antiretroviral therapy in Taiwan. AB - OBJECTIVES: To determine the impact of transmitted drug resistance (TDR) of HIV-1 on treatment outcome in areas where routine testing for drug resistance mutations may not be available before combination antiretroviral therapy (cART) is initiated. METHODS: Genotypic resistance assays were performed on HIV isolates from archived blood samples obtained from 1349 antiretroviral-naive HIV-1 infected patients in Taiwan from 2000 to 2010. Resistance mutations were interpreted with the use of the HIVdb program of the Stanford University HIV Drug Resistance Database. The genotypic sensitivity score (GSS) of the regimens prescribed was calculated. A matched case-control study was conducted to assess the impact of TDR on treatment outcomes. RESULTS: The overall prevalence of TDR to any antiretroviral agent was 8.0%, declining from 12.3% in 2003-06 to 5.1% in 2007-10. In the matched case-control study, 31 patients with high- or intermediate-level resistance, 16 with low-level resistance and 89 controls were enrolled. Compared with regimens with GSS >2.5, initiation of regimens with GSS <=2.5 was associated with a higher treatment failure rate (39.3% versus 15.7%, P = 0.02) and shorter time to treatment failure (log-rank P < 0.001). In patients receiving regimens with GSS <=2.5, protease inhibitor-based regimens were less likely to result in treatment failure, compared with non-nucleoside reverse transcriptase inhibitor-based regimens (hazard ratio 0.26, 95% CI 0.06-1.12, P = 0.07). CONCLUSIONS: In Taiwan the prevalence of TDR of HIV-1 strains declined and stabilized between 2007 and 2010. Receipt of antiretroviral regimens with GSS <=2.5 was associated with poorer treatment responses than regimens with GSS >2.5. PMID- 22302563 TI - Use of dried blood spots for the determination of plasma concentrations of nevirapine and efavirenz. AB - OBJECTIVES: Plasma concentrations are frequently used for therapeutic drug monitoring of antiretroviral drugs. Dried blood spot sampling offers a patient friendly and easy alternative to plasma sampling. However, dried blood spot concentrations are not necessarily equal to plasma concentrations and therefore the objective of this work was to establish the relationship between nevirapine and efavirenz dried blood spot and plasma concentrations to facilitate clinical implementation of dried blood spot sampling. METHODS: Paired dried blood spot and plasma samples were obtained from 40 HIV-infected patients on nevirapine and 40 on efavirenz treatment. All samples were analysed using validated HPLC-tandem mass spectrometry methods for the two matrices. Theoretical plasma concentrations were calculated from dried blood spot concentrations using the formula [dried blood spot concentration/(1 - haematocrit)] * fraction bound to plasma proteins = plasma concentration. Linear regression and Bland-Altman analysis were used to compare the two methods. RESULTS: Dried blood spot and plasma concentrations of nevirapine and efavirenz correlated well (r(2) = 0.867 and 0.972, respectively), although efavirenz dried blood spot concentrations were 39.8% (SD 7.1%) lower than plasma concentrations. Theoretical plasma concentrations (using patient specific haematocrit) of nevirapine and efavirenz were similar to measured plasma concentrations, with a mean difference between the two methods of 0.29 mg/L (SD 1.35 mg/L) and 0.08 mg/L (SD 0.31 mg/L), respectively. CONCLUSIONS: Dried blood spot concentrations of nevirapine and efavirenz were equal to plasma concentrations after correction for haematocrit and compound-specific plasma protein binding and can therefore be used in clinical practice. PMID- 22302564 TI - High burden of transmitted HIV-1 drug resistance in Italian patients carrying F1 subtype. AB - BACKGROUND: Transmitted drug resistance (TDR) is mainly restricted to individuals carrying B subtype, with low prevalence among non-B subtypes when grouped together. Subtype F1 is the most frequent non-B variant found in subjects living in Italy, allowing a specific assessment of TDR associated with this clade. METHODS: We analysed pol sequences of HIV-1-positive individuals carrying the F1 variant included in the Antiretroviral Resistance Cohort Analysis database in the 1998-2009 period. Mutations were analysed with the Surveillance Drug Resistance Mutation and the International AIDS Society lists for naive and treated patients, respectively. RESULTS: Among 343 HIV-1-infected patients carrying an F1 subtype, resistance was evaluated in a subset of 221 patients whose treatment status was known (169 drug naive and 52 drug experienced). The prevalence of TDR was 15.4% (11.8% for nucleoside/nucleotide reverse transcriptase inhibitors, 6.5% for non nucleoside reverse transcriptase inhibitors and 7.1% for protease inhibitors). Among the 169 naive patients, 75.1%, 10.1% and 7.1% were Italians, South Americans and Romanians, respectively. Heterosexuals were prevalent among Italians and Romanians, while men who have sex with men were predominant among South Americans. The overall frequency of TDR declined from 21.4% to 7.1% in the 1998-2009 period. Although no statistical difference was detected, the frequency of TDR was higher in South Americans (23.5%) compared with Italian and Romanian naive patients (15% and 8.3%, respectively). DISCUSSION: Our study shows a remarkable frequency of TDR in the F1 subtype-infected population. The high prevalence of TDR detected in South American subjects is linked to the homosexual route of infection. However, TDR was considerably high also in Italian subjects harbouring the F1 subtype, deserving careful monitoring. PMID- 22302566 TI - A preface to the international forum as a source of diversity opinions. PMID- 22302565 TI - Environmental intervention for house dust mite control in childhood bronchial asthma. AB - OBJECTIVES: This study was carried out to determine the effectiveness of physical and chemical environmental control measures for house dust mites (HDM) in controlling bronchial asthma in children. METHODS: A total of 160 asthmatic children who were sensitized to HDM underwent clinical and environmental assessment. The children were randomly allocated into one of four groups according to the intervention (chemical, physical, both chemical and physical, none) and the effectiveness of the intervention was assessed at 8 and 16 weeks. RESULTS: The group for which physical control measures were used showed significant improvement in all outcome measures, including mean differences of forced expiratory volume after 1 s (FEV1) and peak expiratory flow rate (PEFR), which were 2.05% and 4.65 l/min, respectively, at the 8-week follow-up evaluation. The percentage of severe asthma decreased from 45 to 22%. Similar results were obtained for the group with both chemical (tannic acid) and physical interventions (p < 0.05 for all measures). In the group where tannic acid was used as a chemical measure, the number of children with moderate and severe asthma decreased from 15 in each category to 11 and 7, respectively. In the control group, only the mean difference of PEFR (1.62 l/min) was significant after 16 weeks. Despite these promising findings, only the FEV1 was significantly different (p = 0.014) when the four groups were compared. CONCLUSIONS: Based on these results, we conclude that simple physical control measures have the potential to contribute to the control of asthma symptoms in asthmatic children sensitized to HDM allergen. PMID- 22302567 TI - Membrane-bound toll-like receptors are overexpressed in peripheral blood and synovial fluid mononuclear cells of enthesitis-related arthritis category of juvenile idiopathic arthritis (JIA-ERA) patients and lead to secretion of inflammatory mediators. AB - We examined expression and function of TLRs in enthesitis-related arthritis (ERA) patients. RNA levels of TLR1, TLR3, and TLRs 5-8 were measured in 24 ERA peripheral blood mononuclear cells (PBMC), 18 synovial fluid mononuclear cells (SFMC), and IRAK1, IRAK4, TRIF, TRAF3, and TRAF6 in 18 PBMC and 10 SFMC. IL-6 and IL-8 were measured in supernatants from ERA PBMC (n=7), SFMC (n=3), and healthy PBMC (n=5) cultured with ligands for TLR1/2 (Pam 3-cys), TLR3 (polyI:C), TLR5 (flagellin), and TLR2/6 (zymosan). TLRs 1, 3, 5, and 6 were measured in whole blood (n=20 ERA, seven healthy) and SFMC (n=2) by flow cytometry. ERA PBMC compared to healthy PBMC and SFMC compared to ERA PBMC had higher RNA expression of TLR1, TLR3, TLR5, TLR6, IRAK1, IRAK4, TRIF, TRAF3, and TRAF6. TLR7 and TLR8 RNA expression was similar in all study groups. IL-6 and IL-8 levels were higher in stimulated ERA SFMC compared to ERA PBMC and in ERA PBMC compared to control PBMC. TLRs 1, 3, and 6 were also overexpressed at the protein level. PMID- 22302568 TI - Hadoop-BAM: directly manipulating next generation sequencing data in the cloud. AB - Hadoop-BAM is a novel library for the scalable manipulation of aligned next generation sequencing data in the Hadoop distributed computing framework. It acts as an integration layer between analysis applications and BAM files that are processed using Hadoop. Hadoop-BAM solves the issues related to BAM data access by presenting a convenient API for implementing map and reduce functions that can directly operate on BAM records. It builds on top of the Picard SAM JDK, so tools that rely on the Picard API are expected to be easily convertible to support large-scale distributed processing. In this article we demonstrate the use of Hadoop-BAM by building a coverage summarizing tool for the Chipster genome browser. Our results show that Hadoop offers good scalability, and one should avoid moving data in and out of Hadoop between analysis steps. PMID- 22302569 TI - ArchTEx: accurate extraction and visualization of next-generation sequence data. AB - MOTIVATION: The extension of mapped sequence tags is a common step in the analysis of single-end next-generation sequencing (NGS) data from protein localization and chromatin studies. The optimal extension can vary depending on experimental and technical conditions. Improper extension of sequence tags can obscure or mislead the interpretation of NGS results. We present an algorithm, ArchTEx (Architectural Tag Extender), which identifies the optimal extension of sequence tags based on the maximum correlation between forward and reverse tags and extracts and visualizes sites of interest using the predicted extension. AVAILABILITY AND IMPLEMENTATION: ArchTEx requires Java 1.6 or newer. Source code and the compiled program are freely available at http://sourceforge.net/projects/archtex/ CONTACT: mjbuck@buffalo.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22302570 TI - Retraction. Reconstructing disease phenome-genome association by bi-random walk. PMID- 22302571 TI - Evaluating the Drosophila Bicoid morphogen gradient system through dissecting the noise in transcriptional bursts. AB - MOTIVATION: We describe a statistical model to dissect the noise in transcriptional bursts in a developmental system. RESULTS: We assume that, at any given moment of time, each copy of a native gene inside a cell can exist in either a bursting (active) or non-bursting (inactive) state. The experimentally measured total noise in the transcriptional states of a gene in a population of cells can be mathematically dissected into two contributing components: internal and external. While internal noise quantifies the stochastic nature of transcriptional bursts, external noise is caused by cell-to-cell differences including fluctuations in activator concentration. We use our developed methods to analyze the Drosophila Bicoid (Bcd) morphogen gradient system. For its target gene hunchback (hb), the noise properties can be recapitulated by a simplified gene regulatory model in which Bcd acts as the only input, suggesting that the external noise in hb transcription is primarily derived from fluctuations in the Bcd activator input. However, such a simplified gene regulatory model is insufficient to predict the noise properties of another Bcd target gene, orthodenticle (otd), suggesting that otd transcription is sensitive to additional external fluctuations beyond those in Bcd. Our results show that analysis of the relationship between input and output noise can reveal important insights into how a morphogen gradient system works. Our study also advances the knowledge about transcription at a fundamental level. CONTACT: jun.ma@cchmc.org SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22302572 TI - pymzML--Python module for high-throughput bioinformatics on mass spectrometry data. AB - SUMMARY: pymzML is an extension to Python that offers (i) an easy access to mass spectrometry (MS) data that allows the rapid development of tools, (ii) a very fast parser for mzML data, the standard data format in MS and (iii) a set of functions to compare or handle spectra. AVAILABILITY AND IMPLEMENTATION: pymzML requires Python2.6.5+ and is fully compatible with Python3. The module is freely available on http://pymzml.github.com or pypi, is published under LGPL license and requires no additional modules to be installed. CONTACT: christian@fufezan.net. PMID- 22302573 TI - Gencrypt: one-way cryptographic hashes to detect overlapping individuals across samples. AB - Meta-analysis across genome-wide association studies is a common approach for discovering genetic associations. However, in some meta-analysis efforts, individual-level data cannot be broadly shared by study investigators due to privacy and Institutional Review Board concerns. In such cases, researchers cannot confirm that each study represents a unique group of people, leading to potentially inflated test statistics and false positives. To resolve this problem, we created a software tool, Gencrypt, which utilizes a security protocol known as one-way cryptographic hashes to allow overlapping participants to be identified without sharing individual-level data. PMID- 22302574 TI - Breakpointer: using local mapping artifacts to support sequence breakpoint discovery from single-end reads. AB - SUMMARY: We developed Breakpointer, a fast algorithm to locate breakpoints of structural variants (SVs) from single-end reads produced by next-generation sequencing. By taking advantage of local non-uniform read distribution and misalignments created by SVs, Breakpointer scans the alignment of single-end reads to identify regions containing potential breakpoints. The detection of such breakpoints can indicate insertions longer than the read length and SVs located in repetitve regions which might be missd by other methods. Thus, Breakpointer complements existing methods to locate SVs from single-end reads. AVAILABILITY: https://github.com/ruping/Breakpointer CONTACT: ruping@molgen.mpg.de SUPPLEMENTARY INFORMATION: Supplementary material is available at Bioinformatics online. PMID- 22302575 TI - Predicting kinase substrates using conservation of local motif density. AB - MOTIVATION: Protein kinases represent critical links in cell signaling. A central problem in computational biology is to systematically identify their substrates. RESULTS: This study introduces a new method to predict kinase substrates by extracting evolutionary information from multiple sequence alignments in a manner that is tolerant to degenerate motif positioning. Given a known consensus, the new method (ConDens) compares the observed density of matches to a null model of evolution and does not require labeled training data. We confirmed that ConDens has improved performance compared with several existing methods in the field. Further, we show that it is generalizable and can predict interesting substrates for several important eukaryotic kinases where training data is not available. AVAILABILITY AND IMPLEMENTATION: ConDens can be found at http://www.moseslab.csb.utoronto.ca/andyl/. CONTACT: alan.moses@utoronto.ca SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22302576 TI - Effects of Active and Passive Smoking on Ear Infections. AB - Otitis media (OM) is one of the most frequent diseases in young children, causing to visit a physician, and also the most common indication for antibiotic prescription. The peak incidence and prevalence of OM is 6 to 18 months of age. In children, second-hand smoke (SHS) exposure is associated with upper and lower respiratory tract infections, such as acute otitis media (AOM), pneumonia, and bronchitis. Despite the overwhelming evidence of the role of SHS exposure on infant health, a very high proportion of children still continue to be exposed. This important relationship between all kinds of smoking and poor health may not be appreciated universally. With this article, we aim to review tobacco smoke exposure and OM connection. How this exposure may cause OM especially in young children? What can be done to prevent and to reduce the harmfull effects of tobacco smoking? PMID- 22302577 TI - Emerging Sexual Health Issues Among Women Who Have Sex with Women. AB - Women who have sex with women (WSW) comprise a diverse group of people who evidence a spectrum of sexual identity, sexual behaviors, sexual practices, and risk behaviors. WSW are at risk of acquiring a diversity of sexually transmitted infections (STIs) from current and prior partners, both male and female. Notably, human papillomavirus (HPV) is sexually transmitted between female partners, and Pap smear guidelines should be followed in this group. Bacterial vaginosis is common among WSW. WSW should not be presumed to be at low or no risk for STIs based on sexual orientation, and reporting of same sex behavior by women should not deter providers from considering and performing screening for STIs, including Chlamydia trachomatis, according to current guidelines. Effective delivery of sexual health services to WSW requires a comprehensive and open discussion of sexual and behavioral risks, beyond sexual identity, between care providers and their female clients. PMID- 22302578 TI - Rapid charge transport in dye-sensitized solar cells made from vertically aligned single-crystal rutile TiO(2) nanowires. AB - A rapid solvothermal approach was used to synthesize aligned 1D single-crystal rutile TiO(2) nanowire (NW) arrays on transparent conducting substrates as electrodes for dye-sensitized solar cells. The NW arrays showed a more than 200 times faster charge transport and a factor four lower defect state density than conventional rutile nanoparticle films. PMID- 22302579 TI - Superior mesenteric artery aneurysm in a 9-year-old boy with classical Ehlers Danlos syndrome. AB - A 9-year-old boy with the classical type of Ehlers-Danlos syndrome (EDS) developed a symptomatic aneurysm of the superior mesenteric artery. His EDS diagnosis had been confirmed biochemically and genetically. Vascular complications are known to be associated with the vascular type of EDS, but this is the first report of a child with classical EDS who developed a major vascular complication. Clinicians should be aware that severe vascular complications albeit rare, can also occur in classical EDS. PMID- 22302580 TI - Increased [3H]D-aspartate release and changes in glutamate receptor expression in the hippocampus of the mnd mouse. AB - Neuronal ceroid lipofuscinoses (NCLs) are a group of hereditary childhood diseases characterized mainly by lipopigment accumulation and a multisystemic pattern of symptoms including mental retardation, seizures, motor impairment, and blindness. The mnd mouse, carrying a mutation in the Cln8 gene, has been proposed as a model of epilepsy with mental retardation (EPMR, ornorthern epilepsy). We recently showed neuronal hyperexcitability and seizure hypersusceptibility in mnd mice. To elucidate the cellular mechanisms related to hippocampal hyperexcitability, the glutamatergic transmission and the expression of postsynaptic glutamate receptors were investigated in hippocampus. A significant increase in either spontaneous or KCl-stimulated overflow of [3H]D-aspartate was found in mnd mice compared with controls. This increase was maintained after DL threo-beta-benzyloxyaspartic acid (TBOA) treatment, suggesting a nonrelevant role for transporter-mediated release and supporting the involvement of exocytotic [3H]D-aspartate release. Accordingly, Ca2+-dependent overflow induced by ionomycin was also increased in mnd mice. Levels of glutamate 1-3 AMPA receptor subunits were increased, and levels of the NR2A NMDA receptor subunit were decreased in the hippocampus of mnd mice, suggesting an adaptive response to glutamate overstimulation. PMID- 22302581 TI - Life-threatening cervical spine collapse as a result of postradiation osteonecrosis-case report and review of the literature. AB - BACKGROUND: Mandibular osteoradionecrosis (ORN) is a well-known complication of head and neck radiotherapy; however, ORN of the cervical spine is rarely reported. METHODS: Herein, we present a patient with a history of tonsillar carcinoma treated with chemoradiation who developed acute, severe progressive neck pain due to cervical spine collapse as a result of ORN. We also discuss diagnosis and treatment of cervical ORN based on a review of the literature. RESULTS: The patient was successfully treated with antibiotics and surgical debridement and fixation. CONCLUSION: Delayed diagnosis of cervical ORN can result in marked disability and pain due to spinal cord compression, as well as serious deformity and instability requiring surgical intervention, and even death. It is important for otolaryngologists who treat head and neck malignancies to be aware of this potential complication so that patients may be diagnosed as early as possible and treated with conservative measures. PMID- 22302582 TI - Allogeneic transplantation of umbilical cord-derived mesenchymal stem cells for diffuse alveolar hemorrhage in systemic lupus erythematosus. AB - Umbilical cord-derived mesenchymal stem cell transplantation (UC-MSCT) has been proved to be effective in the treatment of systemic lupus erythematosus (SLE), based on animal experiments and clinical trials. Diffuse alveolar hemorrhage (DAH) is a rare complication of SLE with a high mortality usually over 50%. This study aimed to assess the efficacy of UC-MSCT in the treatment of SLE-associated DAH. Four SLE patients complicated with DAH, who underwent UC-MSCT, were included. Clinical changes before and after transplantation were assessed by measurements of hemoglobin, platelet level, oxygen saturation, and serological factors. High-resolution CT (HRCT) scans of the chest were performed to evaluate pulmonary manifestation. All the four patients showed dramatic improvements of their clinical manifestations. Hemoglobin was elevated after UC-MSCT and was sustained at a normal level 6 months after UC-MSCT in the four patients. Platelet level was upregulated in two patients who had thrombocytopenia at baseline. Oxygen saturation appeared to be normal at 1 month after UC-MSCT, and this result was confirmed by the HRCT scan of the chest. Serum albumin elevated to 3.5 g/dl 6 months after transplantation. Our findings suggest that UC-MSCT results in amelioration of oxygen saturation as well as hematological and serologic changes, which revealed that UC-MSCT could be applied as a salvage strategy for DAH patients. PMID- 22302584 TI - Ligand binding assays in the 21st Century laboratory: automation. PMID- 22302585 TI - Benet L Z and Galeazzi R L: noncompartmental determination of the steady-state volume of distribution, J Pharm Sci 68, 1071-1074, 1979--the backstory. PMID- 22302586 TI - Prospective risk of late stillbirth in monochorionic twins: a regional cohort study. AB - OBJECTIVE: Monochorionic (MC) pregnancies are routinely delivered electively at late preterm gestation with the aim of avoiding stillbirth at term. The aim of this study was to evaluate the prospective risk of late stillbirth in a large regional cohort of twin pregnancies of known chorionicity. METHODS: This was a retrospective study of all twin pregnancy births of known chorionicity between 2000 and 2009 from a large regional cohort consisting of nine hospitals. Prospective risk was calculated per 1000 fetuses rather than pregnancies, as each twin pregnancy had two gestations at risk of stillbirth. RESULTS: A total of 3005 twin pregnancies delivered after 26 weeks' gestation in the Southwest Thames Obstetric Research Collaborative. The total risk of stillbirth after 26 weeks in MC twins (19.1 per 1000 fetuses) was significantly higher than in dichorionic (DC) twins (6.5 per 1000 fetuses), with an odds ratio (OR) of 2.97 (95% CI, 1.71 5.18). The risk of stillbirth in MC twins did not change significantly between 26 weeks (1.8 per 1000 fetuses) and 36 weeks (3.4 per 1000 fetuses), with an OR of 1.85 (95% CI, 0.3-13.2). The equivalent figures for DC twins were 0.6 per 1000 fetuses and 2.1 per 1000 fetuses, respectively (OR, 3.4 (95% CI, 0.9-13.2)). CONCLUSIONS: The risk of stillbirth in MC twins does not appear to increase significantly near term. This may be due to a policy of routine surveillance and elective delivery from 36 weeks. The data do not support a policy of elective delivery before 36 weeks' gestation in MC pregnancies. PMID- 22302587 TI - Technology transfer. PMID- 22302588 TI - Dipolar DC collisional activation in a "stretched" 3-D ion trap: the effect of higher order fields on rf-heating. AB - Applying dipolar DC (DDC) to the end-cap electrodes of a 3-D ion trap operated with a bath gas at roughly 1 mTorr gives rise to 'rf-heating' and can result in collision-induced dissociation (CID). This approach to ion trap CID differs from the conventional single-frequency resonance excitation approach in that it does not rely on tuning a supplementary frequency to coincide with the fundamental secular frequeny of the precursor ion of interest. Simulations using the program ITSIM 5.0 indicate that application of DDC physically displaces ions solely in the axial (inter end-cap) dimension whereupon ion acceleration occurs via power absorption from the drive rf. Experimental data shows that the degree of rf heating in a stretched 3-D ion trap is not dependent solely on the ratio of the dipolar DC voltage/radio frequency (rf) amplitude, as a model based on a pure quadrupole field suggests. Rather, ion temperatures are shown to increase as the absolute values of the dipolar DC and rf amplitude both decrease. Simulations indicate that the presence of higher order multi-pole fields underlies this unexpected behavior. These findings have important implications for the use of DDC as a broad-band activation approach in multi-pole traps. PMID- 22302589 TI - Sodium cation affinities of commonly used MALDI matrices determined by guided ion beam tandem mass spectrometry. AB - The sodium cation affinities of six commonly used MALDI matrices are determined here using guided ion beam tandem mass spectrometry techniques. The collision induced dissociation behavior of six sodium cationized MALDI matrices, Na+(MALDI), with Xe is studied as a function of kinetic energy. The MALDI matrices examined here include: nicotinic acid, quinoline, 3-aminoquinoline, 4 nitroaniline, picolinic acid, and 3-hydroxypicolinic acid. In all cases, the primary dissociation pathway corresponds to endothermic loss of the intact MALDI matrix. The cross section thresholds are interpreted to yield zero and 298 K Na+ MALDI bond dissociation energies (BDEs), or sodium cation affinities, after accounting for the effects of multiple ion-neutral collisions, the kinetic and internal energy distributions of the reactants, and dissociation lifetimes. Density functional theory calculations at the B3LYP/6-311+G(2d,2p)//B3LYP/6-31G* and MP2(full)/6-311+G(2d,2p)//B3LYP/6-31G* levels of theory are used to characterized the structures and energetics for these systems. The calculated BDEs exhibit very good agreement with the measured values for most systems. The experimental and theoretical Na+-MALDI BDEs determined here are compared with those previously measured by cation transfer equilibrium methods. PMID- 22302591 TI - Genome sequence of the fungus Glarea lozoyensis: the first genome sequence of a species from the Helotiaceae family. AB - The anamorphic fungus Glarea lozoyensis mutant strain 74030 is an overproducer of pneumocandin B(0), which is chemically converted into Cancidas, a potent antibiotic against clinically important fungal pathogens. Pneumocandins are acylated, cyclic hexapeptides with unusual hydroxylated amino acids. With the Glarea lozoyensis genome, the first species from the large polyphyletic family Helotiaceae has been sequenced. PMID- 22302592 TI - Fungicide impacts on photosynthesis in crop plants. AB - Fungicides are widely used to control pests in crop plants. However, it has been reported that these pesticides may have negative effects on crop physiology, especially on photosynthesis. An alteration in photosynthesis might lead to a reduction in photoassimilate production, resulting in a decrease in both growth and yield of crop plants. For example, a contact fungicide such as copper inhibits photosynthesis by destroying chloroplasts, affecting photosystem II activity and chlorophyll biosynthesis. Systemic fungicides such as benzimidazoles, anilides, and pyrimidine are also phytotoxic, whereas azoles stimulate photosynthesis. This article focuses on the available information about toxic effects of fungicides on photosynthesis in crop plants, highlighting the mechanisms of perturbation, interaction, and the target sites of different classes of fungicides. PMID- 22302593 TI - Early complications after stoma formation: a prospective cohort study in 100 patients with 1-year follow-up. AB - PURPOSE: This study aims to provide an overview of all complications that may occur after construction of an ileostomy or colostomy (loop or end) in daily practice. METHODS: Between July 2007 and April 2008, all adult patients who underwent any type of intestinal stoma formation were asked to participate in this prospective cohort study. All relevant patient characteristics were gathered.Patients were evaluated for complications eight times in a1-year postoperative period. Enterostomal therapy nurses scored complications on specially designed forms. RESULTS: One hundred patients were included; two patients were lost before initial follow-up (FU). During FU, 21% of the patients deceased, and 15% were lost, physically unable to visit the outpatient clinic or withdrew from FU. In 37% of the patients, bowel continuity was restored. Only 26% of the patients were able to complete FU. Overall, 82% of all the patients had one or more stoma-related complications. Most common complications were skin irritation (55%), fixation problems (46%) and leakage (40%). Superficial necrosis,bleeding and retraction occurred in 20%, 14% and 9% of patients, respectively. More stoma related complications were found in stoma's on inappropriate locations. CONCLUSIONS: In this heterogenic patient population with formation of different stoma types, a high complication rate was detected. PMID- 22302594 TI - Biofilm lifestyle enhances diesel bioremediation and biosurfactant production in the Antarctic polyhydroxyalkanoate producer Pseudomonas extremaustralis. AB - Diesel is a widely distributed pollutant. Bioremediation of this kind of compounds requires the use of microorganisms able to survive and adapt to contaminated environments. Pseudomonas extremaustralis is an Antarctic bacterium with a remarkable survival capability associated to polyhydroxyalkanoates (PHAs) production. This strain was used to investigate the effect of cell growth conditions--in biofilm versus shaken flask cultures--as well as the inocula characteristics associated with PHAs accumulation, on diesel degradation. Biofilms showed increased cell growth, biosurfactant production and diesel degradation compared with that obtained in shaken flask cultures. PHA accumulation decreased biofilm cell attachment and enhanced biosurfactant production. Degradation of long-chain and branched alkanes was observed in biofilms, while in shaken flasks only medium-chain length alkanes were degraded. This work shows that the PHA accumulating bacterium P. extremaustralis can be a good candidate to be used as hydrocarbon bioremediation agent, especially in extreme environments. PMID- 22302595 TI - Degradation of difluorobenzenes by the wild strain Labrys portucalensis. AB - This study focuses on the biodegradation of difluorobenzenes (DFBs), compounds commonly used as intermediates in the industrial synthesis of various pharmaceutical and agricultural chemicals. A previously isolated microbial strain (strain F11), identified as Labrys portucalensis, able to degrade fluorobenzene (FB) as sole carbon and energy source, was tested for its capability to degrade 1,2-, 1,3- and 1,4-DFB in batch cultures. Strain F11 could use 1,3-DFB as a sole carbon and energy source, with quantitative release of fluoride, but 1,4-DFB was only degraded and defluorinated when FB was supplied simultaneously. Growth of strain F11 with 0.5 mM of 1,3-DFB led to stoichiometric release of fluoride ion. The same result was obtained in cultures fed with 1 mM of 1,3-DFB or 0.5 mM of 1,4-DFB, in the presence of 1 mM of FB. No growth occurred with 1,2-DFB as substrate, and degradation of FB was inhibited when supplied simultaneously with 1,2-DFB. To our knowledge, this is the first time biodegradation of 1,3-DFB as a sole carbon and energy source, and cometabolic degradation of 1,4-DFB, by a single bacterium, is reported. PMID- 22302596 TI - Surfactant mediated enhanced biodegradation of hexachlorocyclohexane (HCH) isomers by Sphingomonas sp. NM05. AB - Environmental biodegradation of several chlorinated pesticides is limited by their low solubility and sorption to soil surfaces. To mitigate this problem we quantified the effect of three biosurfactant viz., rhamnolipid, sophorolipid and trehalose-containing lipid on the dissolution, bioavailability, and biodegradation of HCH-isomers in liquid culture and in contaminated soil. The effect of biosurfactants was evaluated through the critical micelle concentration (CMC) value as determined for each isomer. The surfactant increased the solubilization of HCH isomers by 3-9 folds with rhamnolipid and sophorolipid being more effective and showing maximum solubilization of HCH isomers at 40 MUg/mL, compared to trehalose-containing lipid showing peak solubilization at 60 MUg/mL. The degradation of HCH isomers by Sphingomonas sp. NM05 in surfactant amended liquid mineral salts medium showed 30% enhancement in 2 days as compared to degradation in 10 days in the absence of surfactant. HCH-spiked soil slurry incubated with surfactant also showed around 30-50% enhanced degradation of HCH which was comparable to the corresponding batch culture experiments. Among the three surfactants, sophorolipid offered highest solubilization and enhanced degradation of HCH isomers both in liquid medium and soil culture. The results of this study suggest the effectiveness of surfactants in improving HCH degradation by increased bioaccessibility. PMID- 22302597 TI - Fluorescence and electrochemical recognition of nucleosides and DNA by a novel luminescent bioprobe Eu(III)-TNB. AB - The luminescence arising from lanthanide cations offers several advantages over organic fluorescent molecules: sharp, distinctive emission bands allow for easy resolution between multiple lanthanide signals; long emission lifetimes (MUs -ms) make them excellent candidates for time-resolved measurements; and high resistance to photo bleaching allow for long or repeated experiments. A method is presented for determination of nucleosides using the effect of enhancement of fluorescence of the easily accessible europium(III)-TNB in presence of different nucleosides. The latter coordinates to Eu(III) -TNB and enhances its luminescence intensity as a result of the displacement of water from the inner coordination sphere of the central metal. A similar method for the determination of DNA based on the quenching of Eu(III)-TNB has been established. The interaction of Eu(III) 4,4,4 trifluoro-1-(2-naphthyl)1,3-butanedione (TNB) complex with nucleosides (NS) (guanosine, adenosine, cytidine, inosine) and DNA has been studied using normal and time-resolved luminescence techniques. Binding constants were determined at 293 K, 298 K, 303 K, 308 K and 313 K by using Benesi-Hildebrand equation. A thermodynamic analysis showed that the reaction is spontaneous with DeltaG being negative. The enthalpy DeltaH and the entropy DeltaS of reactions were all determined. The formation of binary and ternary complexes of Eu(III) with nucleosides and TNB has been studied potentiometrically at (25.0 +/- 0.1) degrees C and ionic strength I = 0.1 mol.dm(-3) (KNO3) . The formation of the 1:1 binary and 1:1:1 ternary complexes are inferred from the corresponding titration curves. Initial estimates of the formation constants of the resulting species and the protonation constants of the different ligands used have been refined with the HYPERQUAD computer program. Electrochemical investigations for the systems under investigations have been carried out using cyclic voltammetry (CV), differential pulse polarography (DPP), and square wave voltammetry (SWV) on a glassy carbon electrode in I = 0.1 mol/L p-toluenesulfonate as supporting electrolyte. PMID- 22302599 TI - Epigenetics and developmental programming of adult onset diseases. AB - Maternal perturbations or sub-optimal conditions during development are now recognized as contributing to the onset of many diseases manifesting in adulthood. This "developmental programming" of disease has been explored using animal models allowing insights into the potential mechanisms involved. Impaired renal development, resulting in a low nephron number, has been identified as a common outcome that is likely to contribute to the development of hypertension in the offspring as adults. Changes in other organs and systems, including the heart and the hypothalamic-pituitary-adrenal axis, have also been found. Evidence has recently emerged suggesting that epigenetic changes may occur as a result of developmental programming and result in permanent changes in the expression patterns of particular genes. Such epigenetic modifications may be responsible not only for an increased susceptibility to disease for an individual, but indirectly for the establishment of a disease state in a subsequent generation. Further research in this field, particularly examination as to whether epigenetic changes to genes affecting kidney development do occur, are essential to understanding the underlying mechanisms of developmental programming of disease. PMID- 22302600 TI - Palladium-catalyzed amidation by chemoselective C(sp3)-H activation: concise route to oxindoles using a carbamoyl chloride precursor. AB - Quite select: a new strategy was developed for the synthesis of various oxindoles from carbamoyl chlorides. Under the optimum reaction conditions, with Ad(2)PBu as a ligand, tBuCONHOH as an additive, and a CO atmosphere, selective C(sp(3))-H activation proceeded in the presence of a C(sp(2))-H bond. Ad=adamantyl. PMID- 22302601 TI - Targeted therapy in bone and soft tissue sarcoma in children and adolescents. AB - Pediatric soft-tissue and bone sarcomas are a heterogeneous group of tumors of mesenchymal origin which affect approximately 1,500 children in the United States each year. Using multimodal therapy (surgery, radiation, and chemotherapy),the overall 5-year survival rate for children with soft-tissue and bone sarcomas is approximately 60%-70%. However, the prognosis for children with metastatic or recurrent disease is poor; and, furthermore, the improvements in the overall cure rate have slowed. It is highly unlikely that further advances in the treatment of pediatric soft-tissue and bone sarcomas will come from traditional cytotoxic chemotherapy. Based on research advances in understanding the biology of pediatric soft-tissue and bone sarcomas, improved cure rates will likely be driven by new types of treatment which target the specific abnormalities within these tumors. These new targeted therapies may include small molecules, antibodies, or other immunotherapies. This review briefly describes the biology of the major types of pediatric sarcomas, discusses potential targets for new therapy, and highlights some recent and current clinical trials using targeted therapy. PMID- 22302602 TI - Photographs in lunch tray compartments and vegetable consumption among children in elementary school cafeterias. PMID- 22302603 TI - Radiological clues to the early diagnosis of hypochondroplasia in the neonatal period: report of two patients. AB - Hypochondroplasia (HCH) is the mildest phenotype among fibroblast growth factor receptor 3 (FGFR3)-associated skeletal dysplasias. Affected individuals usually presents with mild short stature in preschool age. It was uncommon that a diagnosis of HCH is made in young affected children. Recently, however, prenatal ultrasound (US) has increased likelihood of detecting in utero mild short limbs. There have been a few reports on the early diagnosis of HCH in the neonatal period preceded by a suspicion of skeletal dysplasia on fetal US. However, the proper diagnosis of HCH is hampered by absence of the radiological criteria relevant to age, particularly those in the neonatal period. We report on the clinical and radiological findings in two HCH children with a FGFR3 mutation. In both children, fetal US showed short femora and relatively increased biparietal diameter (BPD). However, postnatal assessment failed to make a specific diagnosis in the neonatal period. The correct diagnosis of HCH was accomplished by reassessment after exacerbation of postnatal short stature. In retrospective radiological review, the radiological findings relevant to HCH were discernible more easily in the neonatal period than at age of 3 years. PMID- 22302604 TI - DAPT protects brain against cerebral ischemia by down-regulating the expression of Notch 1 and nuclear factor kappaB in rats. AB - Gamma-secretase inhibitor, N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S phenylglycine t-butyl ester (DAPT) suppresses the activation of Notch 1 signaling, which is recognized as the cell fate signaling and may participate in inflammatory processes together with NF-kappaB pathway that contributes to the brain damage after stroke. DAPT has important pharmacological roles in many diseases. However, little is known about the effect of DAPT on NF-kappaB during cerebral ischemia. This study investigated the time course expression of Notch 1 and the effects of DAPT on Notch 1 and NF-jB after MCAO. The results showed that Notch 1 signaling was up-regulated at the early stage after MCAO, DAPT down regulated the expression of Notch 1 and NF-kappaB and protected brain from damage caused by MCAO. These results may indicate that the downregulation of Notch 1-NF kappaB pathway after ischemia by administration of DAPT is a potential mechanism for its protection. PMID- 22302605 TI - Hyperparathyroidism-jaw tumor syndrome. AB - BACKGROUND: Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a rare autosomal dominant multiple tumor syndrome characterized by hyperparathyroidism due to single or multiple-gland parathyroid tumor(s). Since it was first described in 1990, the genetics underlying the syndrome have been elucidated and typical clinical presentations are becoming clarified as literature describing this rare entity amasses. METHODS AND RESULTS: A 22-year-old man presented with a 2-year history of fatigue, weight loss, nausea, and vomiting. Anemia workup indicated severe hypercalcemia. Investigations were consistent with a diagnosis of HPT-JT. The patient underwent a total 4-gland parathyroidectomy with single gland reimplantation. CONCLUSION: HPT-JT is a complex syndrome with phenotypic manifestations that can seem physiologically and temporally unrelated. The risk of parathyroid carcinoma is elevated in patients with HPT-JT, necessitating rapid treatment and complete tumor resection to reduce the morbidity and mortality associated with intractable hypercalcemia due to local recurrence or metastatic disease. PMID- 22302606 TI - Ischemic tolerance in the brain: endogenous adaptive machinery against ischemic stress. AB - Although more than 100 drugs have been examined clinically, tissue plasminogen activator remains the only drug approved for the treatment of acute ischemic stroke. Since the discovery of ischemic tolerance, it has been widely recognized that the brain possesses an endogenous protective machinery to protect against ischemic stress. Recent studies have clarified that both the upregulation of neuroprotective signaling and the downregulation of inflammatory or apoptotic pathways are involved equally in the acquisition of ischemic tolerance. The triggering stimuli for ischemic stresses are divided into hypoxic, oxidant/inflammatory, and glutamate stress. Glutamate stress, particularly the synaptic stimulation of the N-methyl-D-aspartate receptor, leads to activation of the cAMP response element-binding protein, which could subsequently induce gene expression of several neuroprotective molecules. Gene reprogramming and metabolic downregulation are intimately involved in ischemic tolerance as well as in hibernation and hypothermia. Micro-RNAs may be a key player for tuning the level of gene expression in ischemic tolerance. Future research should be performed to investigate the most effective combination for brain protection, enhancement of cell survival signaling, and inhibition of the inflammatory or apoptotic pathways. PMID- 22302607 TI - Alginate films containing viable Lactobacillus plantarum: preparation and in vitro evaluation. AB - The objective of the study was to develop calcium alginate films, containing Lactobacillus plantarum ATCC 8040 with preserved and stable viability and antibacterial activity. L. plantarum-loaded films containing different calcium concentrations were physically characterized for mechanical and bioadhesive properties and lactobacilli release. The viability and antibacterial activity of L. plantarum was studied before and after processing, and during 6 months of storage. A multiresistant clinical isolate, VIM-2-metalo-beta-lactamase producing Pseudomonas aeruginosa, was used as an indicator strain. Interference between L. plantarum and films enhanced films elasticity, water absorption ability, release of lactobacilli, and decreased films adherence. A decrease of L. plantarum viability in alginate films (<=1 log unit) was observed after freeze drying. L. plantarum, at cell concentrations of 108 cfu/ml, was inhibitory active. The viability and antibacterial activity of the immobilized lactobacilli remained stable during 6 months of storage. The study has proved the potential of alginate films to deliver L. plantarum in high numbers to individuals. PMID- 22302608 TI - Enucleation of vagal nerve schwannoma using intraoperative nerve monitoring. AB - Vagal nerve schwannomas are rare, benign, neural sheath tumors. The treatment of enlarging or symptomatic vagal nerve schwannomas is surgical resection. Transecting the vagus nerve results in significant morbidity, and attempts at nerve preservation should be made whenever possible. We introduce a nerve-sparing technique using meticulous microsurgical dissection and intraoperative nerve monitoring for vagal schwannomas. A 61-year old patient presented with an enlarging 2-cm right vagal nerve schwannoma. She underwent resection via a transcervical approach. The patient was intubated with an electromyographic (EMG) endotracheal tube that allowed for monitoring of the recurrent laryngeal nerve intraoperatively. A microsurgical subcapsular dissection was performed after branches of the vagus nerve were identified using a nerve probe and preserved. At the conclusion of the resection the nerve was intact and stimulated along its entire course. Postoperatively, the patient had normal vagal nerve function. We introduced the role of intraoperative nerve monitoring using an EMG endotracheal tube for successful enucleation of vagal schwannomas. In conjunction with meticulous microsurgical dissection, nerve monitoring allows for successful preservation of the vagus nerve and decreased postoperative morbidity. PMID- 22302609 TI - Effect of arterioarterial anastomosis on early-onset umbilical artery flow abnormality in a monochorionic-diamniotic twin. PMID- 22302610 TI - The dopamine metabolite aminochrome inhibits mitochondrial complex I and modifies the expression of iron transporters DMT1 and FPN1. AB - Hallmarks of idiopathic and some forms of familial Parkinson's disease are mitochondrial dysfunction, iron accumulation and oxidative stress in dopaminergic neurons of the substantia nigra. There seems to be a causal link between these three conditions, since mitochondrial dysfunction can give rise to increased electron leak and reactive oxygen species production. In turn, recent evidence indicates that diminished activity of mitochondrial complex I results in decreased Fe-S cluster synthesis and anomalous activation of Iron Regulatory Protein 1. Thus, mitochondrial dysfunction could be a founding event in the process that leads to neuronal death. Here, we present evidence showing that at low micromolar concentrations, the dopamine metabolite aminochrome inhibits complex I and ATP production in SH-SY5Y neuroblastoma cells differentiated into a dopaminergic phenotype. This effect is apparently direct, since it is replicated in isolated mitochondria. Additionally, overnight treatment with aminochrome increased the expression of the iron import transporter divalent metal transporter 1 and decreased the expression of the iron export transporter ferroportin 1. In accordance with these findings, cells treated with aminochrome presented increased iron uptake. These results suggest that aminochrome is an endogenous toxin that inhibits by oxidative modifications mitochondrial complex I and modifies the levels of iron transporters in a way that leads to iron accumulation. PMID- 22302611 TI - Depressed neurofilament expression associates with apolipoprotein E3/E4 genotype in maturing human fetal neurons exposed to HIV-1. AB - Exposure of differentiating human neural progenitor cells (NEP) to HIV-1 results in a neuronal"failure to thrive" phenotype characterized by a relative decrease in neurofilament-light (NF-L) expression. However,when NEP were segregated by their apolipoproteinE genotype, differentiating apolipoprotein E3/E4 cells showed reduced NF-L expression upon HIV-1 exposure,but differentiating apolipoprotein E3/E3 or apolipoproteinE4/E4 cells did not. These data suggest that apolipoproteinE genotype is a host factor that could affect the development of neurocognitive dysfunction in HIV-1 infected individuals. PMID- 22302612 TI - A novel full-length isoform of murine pregnancy-specific glycoprotein 16 (psg16) is expressed in the brain but does not mediate murine coronavirus (MHV) entry. AB - The mouse pregnancy-specific glycoprotein 16 (PSG16) has been reported to be an alternative receptor for mouse hepatitis virus (MHV), some strains of which cause encephalitis in mice lacking the canonical receptor CEACAM1a. The known isoforms of PSG16 are N-terminally truncated relative to other PSG family proteins and are expressed in neurons as well as in the placenta. We have cloned a novel full length isoform of psg16 that is also expressed in the brain, placenta, and retina but, like the truncated form, lacks MHV receptor activity when expressed on 293T cells, suggesting that PSG16 does not mediate CEACAM1a-independent spread of MHV. PMID- 22302613 TI - A comparison of the accuracy of self-reported intake with measured intake of a laboratory overeating episode in overweight and obese women with and without binge eating disorder. AB - PURPOSE: Research has demonstrated significant underreporting of food intake in obese individuals with and without binge eating disorder (BED). An improved understanding of the accuracy of self-reported food intake is central to diagnosis of eating disorders and monitoring response to treatment. The purpose was to: (1) confirm those with BED consume significantly more kilocalories (kcal) than overweight/obese controls when instructed to overeat in the laboratory and (2) compare dietary recall data with measured intake. METHODS: Fifteen women fulfilling BED criteria and 17 controls participated in an overeating episode and completed a 24-h dietary recall. RESULTS: BED participants consumed significantly more kilocalories according to both methodologies. The BED group self-reported 90% of the measured intake compared to 98% for the control group. Mean differences between the methods indicated that on average both groups underreported intake; however, the mean difference between methods was significantly greater in the BED group. CONCLUSIONS: Findings confirm that those with BED consume significantly more than controls during a laboratory binge and controls tended to be more accurate in recalling their intake 24 h later. PMID- 22302614 TI - Effect of a combination of genistein, polyunsaturated fatty acids and vitamins D3 and K1 on bone mineral density in postmenopausal women: a randomized, placebo controlled, double-blind pilot study. AB - PURPOSE: Many postmenopausal women desire non-pharmaceutical alternatives to hormone therapy for protection against osteoporosis. Soybean isoflavones, especially genistein, are being studied for this purpose. This study examined the effects of synthetic genistein in combination with other potential bone protective dietary molecules on bone mineral density (BMD) in early postmenopausal women. METHODS: In this 6-month double-blind pilot study, 70 subjects were randomized to receive daily either calcium only or the geniVidaTM bone blend (GBB), which consisted of genistein (30 mg/days), vitamin D3 (800 IU/days), vitamin K1 (150 MUg/days) and polyunsaturated fatty acids (1 g polyunsaturated fatty acids as ethyl ester: eicosapentaenoic acid/docosahexaenoic acid ratio = ~2/1). Markers of bone resorption and formation and BMD at the femoral neck, lumbar spine, Ward's triangle, trochanter and intertrochanter, total hip and whole body were assessed. RESULTS: Subjects supplemented with the GBB (n = 30) maintained femoral neck BMD, whereas in the placebo group (n = 28), BMD significantly decreased (p = 0.007). There was also a significant difference (p < 0.05) in BMD between the groups at Ward's triangle in favor of the GBB group. Bone-specific alkaline phosphatase and N-telopeptide significantly increased in the GBB group in comparison with those in baseline and in the placebo group. The GBB was well tolerated, and there were no significant differences in adverse events between groups. CONCLUSIONS: The GBB may help to prevent osteoporosis and reduce fracture risk, at least at the hip, in postmenopausal women. Larger and longer-term clinical trials are warranted. PMID- 22302615 TI - Accuracy and measures of association of anthropometric indexes of obesity to identify the presence of hypertension in adults: a population-based study in Southern Brazil. AB - PURPOSE: This study proposes to examine the accuracy of four anthropometric indexes of obesity to identify the presence of hypertension and assess differences in the estimation and strength of effect measures of the association between each anthropometric measure and hypertension in Brazilian adults. METHODS: A population-based cross-sectional study was carried out with a sample of 1,720 adults from Florianopolis, Brazil. Receiver operating characteristic (ROC) curves were performed to identify the sensitivity and specificity of the best cutoff values for anthropometric indexes (body mass index-BMI, waist circumference-WC, waist-to height ratio-WHtR and conicity index-C-index) for prediction of hypertension. The associations between anthropometric indexes and hypertension were analyzed by Poisson regression expressed as Prevalence Ratios (95% CI) adjusted for socio-demographic variables, health behavior, height, and anthropometric indexes. RESULTS: Of the four anthropometric indexes studied, BMI, WC, and WHtR were found to have the largest areas under the ROC curve relative to hypertension in both sexes. The cutoff values in women and men associated with presence of hypertension were BMI of 24.9 and 24.6 kg/m(2), WC of 86.2 and 89.5 cm, WHtR of 0.49 and 0.50, and C-index of 1.15 and 1.18, respectively. WC and BMI had greater magnitude of association with presence of hypertension, adjusting for socio-demographic variables, health behavior, height, and anthropometric indexes in women and men, respectively. CONCLUSIONS: Anthropometric indexes provide an effective, simple, inexpensive, and non-invasive means for a first-level screening for hypertension. PMID- 22302616 TI - Vitamin D status: sunshine is nice but other factors prevail. PMID- 22302617 TI - Treatment for vitamin D deficiency: here and there do not mean everywhere. PMID- 22302618 TI - Measuring preference-based quality of life in children aged 6-7 years: a comparison of the performance of the CHU-9D and EQ-5D-Y--the WAVES pilot study. AB - PURPOSE: To examine the performance of the child health utility 9D (CHU-9D) and EuroQol 5D-youth (EQ-5D-Y) in children aged 6-7 years. METHOD: The CHU-9D and EQ 5D-Y were interviewer-administered to 160 children aged 6-7 years at six schools across the West Midlands. Missing values, time taken to complete instruments and interviewer ratings were recorded to assess feasibility/acceptability. Construct validity was assessed by testing convergent validity hypotheses. Reliability was examined via a test-retest of a sub-sample. Psychometric properties were further examined by exploring distributions of utility scores, qualitative notes and design of the questionnaires. RESULTS: No missing responses were recorded with over 80% of children's understanding being rated as good/excellent for both questionnaires. The average completion time for both instruments was less than 3 minutes, demonstrating excellent feasibility/acceptability. Evidence of construct validity was recorded with 12 of the 13 convergent hypotheses being supported. Test-retest reliability was relatively poor for both instruments with weighted kappa coefficients ranging from fair to moderate. CONCLUSION: Children aged 6-7 years can feasibly complete utility instruments when interviewer-administered. The reliability of the instruments is of concern and requires further study. With respect to content validity and other psychometric properties, the CHU-9D is favoured to the EQ-5D-Y. Until the EuroQol group produces tariff values for the EQ-5D-Y, we recommend that the EQ-5D-Y is not used for utility elicitation in this age group. PMID- 22302619 TI - A procedure for obtaining impact of cancer version 2 scores using version 1 responses. AB - PURPOSE: Psychometric scales often change over time, complicating comparison of scores across different versions. The Impact of Cancer (IOC) scale was developed to measure quality of life of long-term cancer survivors. We sought to develop a method for scoring the earlier version, IOCv1, to obtain scores comparable to IOCv2, which is the recommended version. METHODS: Data from 1,828 cancer survivors who had completed a questionnaire including all IOCv1 and IOCv2 items were randomly split into training, validation and test sets. The training and validation sets were used to develop and validate linear regression models for predicting each IOCv2 item missing from IOCv1. The models were then applied to the test set to obtain pseudo-IOCv2 scores, which were compared to observed scores to assess predictive performance of the models in independent data. RESULTS: Observed and pseudo-IOCv2 scale scores were highly correlated in the test sample and had mean differences near zero. The models performed especially well in predicting summary scale scores, with correlations exceeding 0.98. CONCLUSIONS: The approach facilitates comparison across samples of survivors surveyed using different versions of the IOC and may be useful to other investigators trying to compare participants surveyed using different versions of the same instrument. PMID- 22302620 TI - Genetic counseling as a tool for type 2 diabetes prevention: a genetic counseling framework for common polygenetic disorders. AB - Advances in genetic epidemiology have increased understanding of common, polygenic preventable diseases such as type 2 diabetes. As genetic risk testing based on this knowledge moves into clinical practice, we propose that genetic counselors will need to expand their roles and adapt traditional counseling techniques for this new patient set. In this paper, we present a genetic counseling intervention developed for a clinical trial [Genetic Counseling/Lifestyle Change for Diabetes Prevention, ClinicalTrials.gov identifier: NCT01034319] designed to motivate behavioral changes for diabetes prevention. Seventy-two phenotypically high-risk participants received counseling that included their diabetes genetic risk score, general education about diabetes risk factors, and encouragement to participate in a diabetes prevention program. Using two validated genetic counseling scales, participants reported favorable perceived control and satisfaction with the counseling session. Our intervention represents one model for applying traditional genetic counseling principles to risk testing for polygenetic, preventable diseases, such as type 2 diabetes. PMID- 22302621 TI - Direct-to-consumer personal genomic testing: a case study and practical recommendations for "genomic counseling". AB - Technological advances and information-seeking consumers have pushed forward the movement of direct-to consumer(DTC) genetic testing. Just like with other types of testing, there are potential risks, benefits and limitations. A major limitation of DTC testing is the incomplete view it provides regarding lifetime risk for common, complex diseases,since most tests only analyze 1-2 single nucleotide polymorphisms (SNPs) and do not include evaluation of medical or family histories, which is necessary to risk assessment. Further, it is not currently well-established whether personal genomic testing results will lead toward improved health behaviors, adverse psychological effects or potential overuse of the health care system. To display these and other issues, we present an in-depth case study of an individual who ordered DTC genetic testing and subsequently sought genetic counseling. This case presents a unique learning experience for the field of genomic counseling, as the patient did not fit the typical assumptions regarding 'early adopters' of DTC testing. It also allowed the genetics health care providers involved in the case to identify gaps in current genetic counseling practice that need to be filled and approaches to employ for successful delivery of genomic counseling. Based on our experience, we developed practical recommendations for genomic counseling, which include novel approaches to case preparation, use of electronic tools during the counseling session, and focusing on education as the major component of the genomic counseling session, in order to provide patients with the knowledge necessary to independently interpret and understand large amounts of genomic testing information provided to them. PMID- 22302622 TI - The clinical spectrum of juvenile idiopathic arthritis in a large urban population. AB - Urban populations present particular challenges for medical providers. Patients are extremely diverse, with varied socioeconomic, cultural, and ethnic backgrounds. Physicians caring for children with juvenile idiopathic arthritis must be prepared to interact effectively with many types of families who bring with them varied experiences and expectations. Pediatric rheumatologists should be familiar with patient characteristics that can influence disease outcomes. Access to care is affected by place of residence, referral delays, parental education, and the child's insurance status. Patients of different ethnic backgrounds vary in their trust of physicians and health systems. Understanding of risk in medical decision making is influenced by ethnicity as well. Adherence also varies by ethnic group, with African American patients reporting lower adherence than Caucasian patients. Issues of doctor- patient communication and use of complementary and alternative medicine are also affected by cultural factors. Especially for physicians working in a large metropolitan area, an understanding of societal factors influencing patient behavior is essential to provide optimal care for children with juvenile idiopathic arthritis. PMID- 22302623 TI - Synthesis of cyclic peptides and cyclic proteins via ligation of peptide hydrazides. AB - Intramolecular ligation of peptide hydrazides is reported to occur readily, causing the lactamization of fully unprotected peptides in an epimerization-free manner. This method relies on the routine procedures of Fmoc solid-phase peptide synthesis. It can be used to prepare cyclic peptides and cyclic proteins under simpler, mild conditions at lower costs. PMID- 22302624 TI - Circulating concentrations, cerebral output of the CINC-1 and blood-brain barrier disruption in Wistar rats after pneumococcal meningitis induction. AB - Pneumococcal meningitis is a severe infectious illness of the central nervous system (CNS), with high rates of lethality and morbidity, being that the microorganism and the host's inflammatory response are responsible for cerebral complications. Moreover, the blood-brain barrier (BBB) itself secretes cytokines and, because of the bipolar nature of the BBB, these substances can be secreted into either the CNS compartment or in the blood, so patients with acute bacterial meningitis frequently develop sepsis. Therefore, the aim of this study was to evaluate the cytokine/chemokine levels in different vessels and the BBB integrity after pneumococcal meningitis induction. Wistar rats were infected with Streptococcus pneumoniae, and the BBB integrity was investigated using Evan's blue dye. Also, blood from the carotid artery and jugular vein was collected in order to perform tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL 1beta), interleukin-6 (IL-60 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) analyses by enzyme-linked immunosorbent assay (ELISA). CINC-1 levels were increased at 6 h in the arterial plasma and at 3 and 6 h in the jugular plasma. We observed BBB breakdown between 12 and 24 h in the hippocampus and at 12 and 18 h in the cortex after pneumococcal meningitis induction. The increase of CINC-1 occurred prior to the BBB breakdown. CINC-1 is a neutrophil chemoattractant and it may be related to early events in the pneumococcal meningitis pathophysiology. PMID- 22302625 TI - Venous thromboembolism in patients with head and neck cancer after surgery. AB - BACKGROUND: The purpose of this study was to report the incidence of venous thromboembolism (VTE) in patients with head and neck cancer after surgery. METHODS: This was a single-institution, retrospective cohort: 134 patients underwent resection and simultaneous microvascular reconstruction. The primary endpoint was identification of confirmed or suspicious VTE within 30 days of surgery. RESULTS: Two subjects (1.4%) with confirmed VTE (1 pulmonary embolism, 1 deep venous thrombosis) and 6 subjects (4.4%) with suspicious VTE (1 acute respiratory failure, 1 sudden cardiac arrest, and 4 cases of leg edema without imaging) were identified. The strongest predictors of possible VTE were prior VTE (p = .004; odds ratio [OR], 25.11; 95% confidence interval [CI], 1.13-556.40), red cell transfusion (p = .009; OR, 1.80; 95% CI, 1.16-2.80), high body mass index (p = .015, OR, 1.29, 95% CI, 1.05-1.58), and older age (p = .046; OR, 1.10; 95% CI, 1.00-1.19). CONCLUSION: The incidence of VTE in patients with head and neck cancer after resection and microvascular reconstruction ranged from 1.4% to 5.8%. PMID- 22302626 TI - Cellular mechanisms of plasmalemmal sealing and axonal repair by polyethylene glycol and methylene blue. AB - Mammalian neurons and all other eukaryotic cells endogenously repair traumatic injury within minutes by a Ca2+-induced accumulation of vesicles that interact and fuse with each other and the plasmalemma to seal any openings. We have used uptake or exclusion of extracellular fluorescent dye to measure the ability of rat hippocampal B104 cells or rat sciatic nerves to repair (seal) transected neurites in vitro or transected axons ex vivo. We report that endogenous sealing in both preparations is enhanced by Ca2+-containing solutions and is decreased by Ca2+-free solutions containing antioxidants such as dithiothreitol (DTT), melatonin (MEL), methylene blue (MB), and various toxins that decrease vesicular interactions. In contrast, the fusogen polyethylene glycol (PEG) at 10-50 mM artificially seals the cut ends of B104 cells and rat sciatic axons within seconds and is not affected by Ca2+ or any of the substances that affect endogenous sealing. At higher concentrations, PEG decreases sealing of transected axons and disrupts the plasmalemma of intact cells. These PEG-sealing data are consistent with the hypothesis that lower concentrations of PEG directly seal a damaged plasmalemma. We have considered these and other data to devise a protocol using a well-specified series of solutions that vary in tonicity, Ca2+, MB, and PEG content. These protocols rapidly and consistently repair (PEG-fuse) rat sciatic axons in completely cut sciatic nerves in vivo rapidly and dramatically to restore long-lasting morphological continuity, action potential conduction, and behavioral functions. PMID- 22302627 TI - Chromosome 4q deletion syndrome: narrowing the cardiovascular critical region to 4q32.2-q34.3. AB - The 4q deletion syndrome is a rare chromosome deletion syndrome with a wide range of clinical phenotypes. There is limited clinical phenotype and molecular correlation for congenital heart defects (CHDs) reported so far for this region primarily because many cases are large deletions, often terminal, and because high-resolution array has not been reported in the evaluation of this group of patients. CHDs are reported in about 60% of patients with 4q deletion syndrome, occurring in the presence or absence of dHAND deletion, implying the existence of additional genes in 4q whose dosage influences cardiac development. We report an 8-month-old patient with a large mid-muscular to outlet ventricular septal defect (VSD), moderate-sized secundum-type atrial septal defect (ASD), thickened, dysplastic pulmonary valve with mild stenosis and moderate pulmonic regurgitation, and patent ductus arteriosus (PDA). Illumina CytoSNP array analysis disclosed a de novo, heterozygous, interstitial deletion of 11.6 Mb of genomic material from the long arm of chromosome 4, at 4q32.3-q34.3 (Chr4:167236114-178816031; hg18). The deleted region affects 37 RefSeq genes (hg18), including two provisional microRNA stemloops. Three genes in this region, namely TLL1 (Tolloid-like-1), HPGD (15-hydroxyprostaglandin dehydrogenase), and HAND2 (Heart and neural crest derivatives-expressed protein 2), are known to be involved in cardiac morphogenesis. This report narrows the critical region responsible for CHDs seen in 4q deletion syndrome. PMID- 22302628 TI - A rural community intervention targeting biomass combustion sources: effects on air quality and reporting of children's respiratory outcomes. AB - OBJECTIVE: Improvements in urban air quality are largely driven by controls on industrial and mobile source emissions, but such factors may have limited influence on many rural environments where biomass combustion (eg, wood stoves) serves as the primary source of fine particulate matter (PM(2.5)). The authors tracked changes in children's respiratory health during a wood stove intervention in a rural mountain valley community heavily impacted by wood smoke-derived PM(2.5). METHODS: Community-wide impacts on children's health were assessed by prospectively collecting surveys from parents of school children during four winter periods in Libby, Montana. Generalised estimating equations with a logit link were used to estimate the effect of reduction in ambient PM(2.5) on wheeze prevalence and other reported symptoms and infections. RESULTS: Over 1100 wood stoves were replaced with new lower emission wood stoves or other heating sources. Ambient PM(2.5) was 27.6% lower in the winters following the changeout programme compared with baseline winters. There was a 26.7% (95% CI 3.0% to 44.6%) reduced odds of reported wheeze for a 5 MUg/m(3) decrease in average winter PM(2.5). Lower ambient PM(2.5) was also associated with reduced odds for reported respiratory infections, including cold (25.4% (95% CI 7.6% to 39.7%)), bronchitis (54.6% (95% CI 24.2% to 72.8%)), influenza (52.3% (95% CI 42.5% to 60.5%)) and throat infection (45.1% (95% CI 29.0% to 57.6%)). CONCLUSION: This wood stove intervention provided a unique opportunity to prospectively observe health benefits resulting from a targeted air pollution reduction strategy in a rural community. PMID- 22302629 TI - Does self-reported computer work add biologically relevant information beyond that of objectively recorded computer work? PMID- 22302630 TI - Neurodevelopmental delay in small babies at term: a systematic review. AB - OBJECTIVE: Being small for gestational age (SGA) or having fetal growth restriction (FGR) may be associated with poorer neurodevelopmental outcomes compared to being appropriate for gestational age (AGA). The aim of this paper was to evaluate the existence and magnitude of decrease in neurodevelopmental scores in SGA and FGR infants born at term from a systematic review of the existing literature. METHODS: Studies of neurodevelopment in SGA/FGR babies were identified from a search of the internet scientific databases. Studies that included preterm births and those that did not define absolute indices of standardized cognitive outcome were excluded. SGA was defined as birth weight below the 10(th) centile for gestation and FGR as the same birth-weight standard with abnormal umbilical artery Doppler ultrasound or evidence of abnormal placentation on pathology specimen studies. Effect size was calculated as the standardized mean difference between neurodevelopment scores of controls and SGA/FGR children. RESULTS: There were 28 studies of SGA, with a total of 7861 SGA and 91 619 control AGA babies, and three studies of FGR, with a total of 119 FGR and 49 control AGA babies. Data synthesis showed that standardized neurodevelopmental scores in SGA babies were 0.32 SD (95% CI, 0.25-0.38) below those for normal controls, though with heterogeneity between studies (I(2) = 68.3%). Insufficient data were available for FGR babies. CONCLUSION: The findings of the study demonstrate that among babies born at term, being SGA is associated with lower scores on neurodevelopmental outcomes compared to AGA controls. A trial designed to evaluate the effects of intervention in small fetuses born at term in order to improve the neurodevelopmental outcome is urgently needed. PMID- 22302631 TI - Lack of cardiac nerve sprouting after intramyocardial transplantation of bone marrow-derived stem cells in a swine model of chronic ischemic myocardium. AB - Previous experimental studies suggested that mesenchymal stem cell transplantation causes cardiac nerve sprouting; however, whether bone marrow (BM) derived mononuclear cells (MNC) and endothelial progenitor cells (EPC) can also lead to cardiac nerve sprouting and alter gap junction expression remains unclear. We investigated the effect of electroanatomical mapping-guided direct intramyocardial transplantation of BM-MNC (n = 8) and CD31+EPC (n = 8) compared with saline control (n = 8) on cardiac nerve sprouting and gap junction expression in a swine model of chronic ischemic myocardium. At 12 weeks after transplantation, the distribution and density of cardiac nerve sprouting were determined by staining of tyrosine hydroxylase (TH) and growth associated protein 43(GAP-43) and expression of connexin 43 in the targeted ischemic and remote normal myocardium. After 12 weeks, no animal developed sudden death after the transplantation. There were no significant differences in the number of cells with positive staining of TH and GAP-43 in the ischemic and normal myocardium between three groups. Furthermore, expression of connexin 43 was also similar in the ischemic and normal myocardia in each group of animals (P > 0.05). The results of this study demonstrated that intramyocardial BM-derived MNC or EPC transplantation in a large animal model of chronic myocardial ischemia was not associated with increased cardiac nerve sprouting over the ischemic myocardium. PMID- 22302632 TI - Specificity and transfer effects in time production skill: examining the role of attention. AB - Two experiments examined transfer of a prospective, time production skill under conditions involving changes in concurrent task requirements. Positive transfer of the time production skill might be expected only when the attentional demands of the concurrent task were held constant from training to test. However, some positive transfer was found even when the concurrent task at retraining was made either easier or more difficult than the concurrent task learned during training. The amount and direction of transfer depended more on the pacing of the stimuli in the secondary task than on the difficulty of the secondary task, even though difficulty affects attentional demands more. These findings are consistent with the procedural reinstatement principle of skill learning, by which transfer from one task to another depends on an overlap in procedures required by the two skills. PMID- 22302634 TI - A functional variation in the hypocretin neuropeptide precursor gene may be associated with obstructive sleep apnea syndrome in Japan. AB - OBJECTIVES/HYPOTHESIS: To evaluate the association of hypocretin neuropeptide precursor gene (HCRT) variations with obstructive sleep apnea syndrome (OSAS) in a cohort of Japanese patients and to further evaluate whether the significant HCRT variations have potential functional consequences on HCRT expression. STUDY DESIGN: Case-control genetic association study. METHODS: We studied the genetic variations within the HCRT gene. The study population consisted of 100 OSAS patients and 100 control subjects. The HCRT gene was amplified by polymerase chain reaction in all study subjects followed by direct sequencing and analysis of sequencing data. RESULTS: Two genetic variations within the HCRT intron, IVS1+16T>C (rs9902709) and IVS1-69G>C, were identified with significant differences between patients and controls (P < .05). A reporter gene assay using HeLa cells showed that the construct containing the C allele of the rs9902709 variation had significantly higher luciferase activity compared with the construct containing the T allele (P = .002). Furthermore, enzyme immunoassay revealed that subjects with T/C and C/C genotypes for rs9902709 had 1.4-fold and 1.5-fold increases in sera levels of orexin-A, respectively. CONCLUSIONS: Our genetic association study, followed by functional and quantitative phenotyping assays, demonstrated a functional locus within the HCRT gene, which may act to increase HCRT expression and lead to a protective effect against the development of OSAS. PMID- 22302635 TI - Improving test properties for neonatal cystic fibrosis screening in the Netherlands before the nationwide start by May 1st 2011. AB - When new technical possibilities arise in health care, often attunement is needed between different actors from the perspectives of research, health care providers, patients, ethics and policy. For cystic fibrosis (CF) such a process of attunement in the Netherlands started in a committee of the Health Council on neonatal screening in 2005. In the balancing of pros and cons according to Wilson and Jungner criteria, the advantages for the CF patient were considered clear, even though CF remains a severe health problem with treatment. Nevertheless, screening was not started then, mainly since the specificity of the tests available at that time was considered too low. Many healthy infants would have been referred for sweat testing and much uncertainty would arise in their parents. Also the limited sensitivity for immigrants and the detection of less severe phenotypes and carriers were considered problematic. The Health Council recommended a pilot screening project which was subsequently performed in some provinces, leading to a 4-step protocol: IRT, PAP, screening for a CFTR mutation panel, and sequencing of the CFTR gene. This would lead to the identification of 23 cases of classical CF, two infants with less severe forms and 12 carriers per year in the Netherlands. Thus many CF patients can be diagnosed early, while limiting the number of referrals, the number of infants with less severe forms diagnosed and the number of carriers identified. Technical solutions were found to limit the ethical problems. A nationwide program using this four step protocol started by 1 May 2011. PMID- 22302636 TI - Biochemical predictors of cardiac rhythm at 1 year follow-up in patients with non valvular atrial fibrillation. AB - C-reactive protein (CRP) is increased in patients with atrial fibrillation (AF) and it might predict the lack of sinus rhythm maintenance in the long term follow up. Scarce data have been reported relating endothelial dysfunction and/or haemostatic or platelet markers to sinus rhythm maintenance in AF patients. We aimed to determine whether some biochemical markers including soluble thrombomodulin (sTM), soluble P-selectin, thrombin-antithrombin (TAT) complex and CRP levels could predict sinus rhythm maintenance at 1 year follow-up in non valvular AF patients. 130 patients (70 males, mean age 67 +/- 13 years) with newly diagnosed AF naive of antithrombotic or antiplatelet therapy were studied. Baseline CRP, P-selectin, sTM and TAT levels were compared to those of 20 matched healthy subjects in sinus rhythm. AF patients had significantly higher plasma CRP (10.5 +/- 2.2 vs 3.25 +/- 0.3 mg/l, p = 0.001), P-selectin (219 +/- 141 vs 126 ng/ml, p = 0.01), and TAT (54 +/- 237 vs 2.7 +/- 3.3 ng/l, p = 0.001) levels compared with controls. Soluble TM levels, although higher than controls, did not reach statistical significance. Multivariate regression analyses showed that elevated CRP (OR = 4.8, p = 0.02) and sTM (OR = 1.05, p = 0.04) were the only two predictors of lack of sinus rhythm at 1 year follow-up. An altered inflammatory, haemostatic, endothelial and platelet environment exists in newly diagnosed AF patients. CRP and sTM levels might be used as biochemical markers to predict the status of cardiac rhythm at 1 year follow-up in some AF patients. PMID- 22302637 TI - Apparent heparin resistance in a patient with infective endocarditis secondary to elevated factor VIII levels. AB - Heparin resistance (HR) is defined as increasing requirements of heparin to maintain a therapeutic activated partial thromboplastin time (aPTT). It is commonly associated with antithrombin deficiency, increased heparin clearance and elevations in heparin binding proteins. Elevated factor VIII levels can cause decrease the aPTT levels (anticoagulant effect) without disturbing heparin activity measured by anti-Xa assay (antithrombotic effect) leading to an apparent heparin resistant state rather than a true heparin resistance. We highlight the importance of increasing awareness of apparent HR and early distinction from true resistance to avoid major life threatening hemorrhagic complications. We hereby report an unusual case of heparin resistance due to increased factor VIII levels in an elderly male with infective endocarditis. PMID- 22302638 TI - Lasers for the treatment of intraocular tumors. AB - Lasers are used extensively in ophthalmology for a variety of conditions, including many choroidal and retinal tumors. With technologic advances, current therapy attempts not only to maximize survival with globe-salvaging treatment, but also to preserve vision. Each neoplasm has different indications for primary and adjuvant therapy, as well as differing laser treatment protocols. Additionally, there are numerous laser applications available for use, including laser photocoagulation, transpupillary thermotherapy (TTT), and photodynamic therapy (PDT). The current review outlines the basic principles of laser treatment for intraocular tumors, focusing on the indications, treatment protocols, efficacy, and safety, while also presenting the latest advances in intraocular tumor treatment. PMID- 22302639 TI - Acute Treatment Options for Spinal Cord Injury. AB - OPINION STATEMENT: Most treatment options for acute traumatic spinal cord injury (SCI) are directed at minimizing progression of the initial injury and preventing secondary injury. Failure to adhere to certain guiding principles can be detrimental to the long-term neurologic and functional outcome of these patients. Therapy for the hyperacute phase of traumatic SCI focuses on stabilizing vital signs and follows the Advanced Trauma Life Support (ATLS) algorithm for ensuring stability of airway, breathing and circulation, and disability (neurologic evaluation)-with spinal stabilization-and exposure. Spinal stabilization, with cervical collars and long backboards, is used to prevent movement of a potentially unstable spinal column injury to prevent further injury to the spinal cord and nerve roots, especially during prehospital transport. Surgery to stabilize the spine is undertaken after life-threatening injuries (hemorrhage, evacuation of intracranial hemorrhage, acute vascular compromise) are addressed. Intensive care unit (ICU) admission is to be considered for all patients with high SCI or hemodynamic instability, as well as those with other injuries that independently warrant ICU admission. Avoidance of hypotension and hypoxia may minimize secondary neurologic injury. Elevating the mean arterial pressure above 85 mmHg for 7 days should be considered, to allow for spinal cord perfusion. The use of intravenous steroids (methylprednisolone) is controversial. Early tracheostomy in patients with lesions above C5 may reduce the number of ventilator days and the incidence of ventilator-associated pneumonia. Select patients may benefit from the placement of a diaphragmatic pacer. Aggressive measures, including CoughAssist and Intermittent Positive Pressure Breaths (IPPB), should be used to maintain lung recruitment and aid in the mobilization of secretions. Some patients with high SCI who are dependent on mechanical ventilation can eventually be liberated from the ventilator with consistent efforts from both the patient and the caregiver, along with some patience. Intermittent catheterization by the patient or a caregiver may be associated with a lower incidence of urinary tract infections, compared with an in-dwelling urinary catheter. Early mobilization of patients and a multidisciplinary approach (including respiratory therapists, nutritional experts, physical therapists, and occupational therapists) can streamline care and may improve long-term outcomes. A number of investigational drugs and therapies offer hope of neurologic recovery for some patients. PMID- 22302640 TI - Design of photocontrolled RNA-binding peptidomimetics. AB - Positively constrained: the first examples of photocontrolled RNA binding peptides are described. The large number of positively charged sides chains in the Rev response element (RRE) of an HIV type I targeting alpha-helix imposes constraints on the choice of azobenzene-derived crosslinker. PMID- 22302641 TI - Unilateral neck therapy in the human papillomavirus ERA: accepted regional spread patterns. AB - BACKGROUND: The purpose of this study was to determine whether the incidence of bilateral neck disease tonsillar cancer is rising. METHODS: We reviewed tonsillar cancer incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. RESULTS: The annual incidence of advanced neck disease (>=N2) with small primary tonsillar cancer is increasing (annual percent change [APC]; p < .05) during 2 evaluable time frames (1988-2003 and 2004-2008). The increase for small primary tonsillar cancer from 2004 to 2008 is associated with increased ipsilateral disease (ie, T1-2N2a-b, APC 10.6%; p < .05) rather than bilateral neck disease (T1-2N2c, APC 5.9%, APC = NS). The increase in bilateral neck disease is less than the overall rise in T1 to 2 tonsillar cancer (APC 7.2%; p < .05). CONCLUSION: In the human papillomavirus (HPV) era, bilateral neck disease is increasingly common. This seems to be a consequence of the increasing incidence of tonsillar cancer rather than a new biologic behavior. PMID- 22302642 TI - Family history of cleft lip and palate in subjects diagnosed with leukemia. PMID- 22302643 TI - Clinical importance of androgen receptor in breast cancer patients treated with adjuvant tamoxifen monotherapy. AB - BACKGROUND: Despite many studies, the clinicopathological importance of the androgen receptor (AR) in breast cancer is not well established, and its significance as an independent predictor of clinical outcome is controversial. A large and systematic study is needed to address these issues. The aim of the present study was to elucidate whether AR has independent clinical value, examining its importance in a large and well-predefined patient group with a long follow-up period and complete clinicopathological data. METHODS: Archival materials of 403 invasive breast cancers from women treated with adjuvant tamoxifen monotherapy (median follow-up period 11.0 years) were subjected to immunohistochemical study using anti-AR monoclonal antibody. AR expression was compared with established clinicopathological factors, estrogen receptor (ER) beta expression, and clinical outcome. RESULTS: AR positivity was correlated with ER-alpha positivity, progesterone receptor positivity, ER-beta positivity, and a lower nuclear grade. Patients with AR-positive carcinomas exhibited a significantly better clinical outcome than those with AR-negative carcinomas (P = 0.0165 for disease-free survival, P = 0.0344 for overall survival). Multivariate analysis did not yield significant differences in clinical outcome according to the AR status, whereas the ER-beta status showed significant differences in multivariate analysis. CONCLUSIONS: Although, and in agreement with previous reports, AR positivity correlated with some established favorable prognostic factors and with ER-beta positivity, AR was not an independent predictor of clinical outcome. Controversy regarding the value of AR as an independent predictor of clinical outcome may at least partly reflect the relatively limited power of AR in breast cancer. PMID- 22302644 TI - An optimal adjustment procedure to minimize experiment time in decisions with multiple alternatives. AB - Decisions between multiple alternatives typically conform to Hick's Law: Mean response time increases log-linearly with the number of choice alternatives. We recently demonstrated context effects in Hick's Law, showing that patterns of response latency and choice accuracy were different for easy versus difficult blocks. The context effect explained previously observed discrepancies in error rate data and provided a new challenge for theoretical accounts of multialternative choice. In the present article, we propose a novel approach to modeling context effects that can be applied to any account that models the speed accuracy trade-off. The core element of the approach is "optimality" in the way an experimental participant might define it: minimizing the total time spent in the experiment, without making too many errors. We show how this approach can be included in an existing Bayesian model of choice and highlight its ability to fit previous data as well as to predict novel empirical context effects. The model is shown to provide better quantitative fits than a more flexible heuristic account. PMID- 22302645 TI - The relationship between color-object associations and color preference: further investigation of ecological valence theory. AB - Ecological valence theory (EVT; Palmer & Schloss, Proceedings of the National Academy of Sciences 107:8877-8882, 2010) proposes that color preferences are due to affective responses to color-associated objects: That is, people generally like colors to the degree that they like the objects associated with those colors. Palmer and Schloss found that the average valence of objects associated with a color, when weighted by how well the objects matched the color (weighted affective valence estimates: WAVE) explained 80% of the variation in preference across colors. Here, we replicated and extended Palmer and Schloss's investigation to establish whether color-object associations can account for sex differences in color preference and whether the relationship between associated objects and color preference is equally strong for males and females. We found some degree of sex specificity to the WAVEs, but the relationship between WAVE and color preference was significantly stronger for males than for females (74% shared variance for males, 45% for females). Furthermore, analyses identified a significant inverse relationship between the number of objects associated with a color and preference for the color. Participants generally liked colors associated with few objects and disliked colors associated with many objects. For the sample overall and for females alone, this association was not significantly weaker than the association of the WAVE and preference. The success of the WAVE at capturing color preference was partly due to the relationship between the number of associated objects and color preference. The findings identify constraints of EVT in its current form, but they also provide general support for the link between color preference and color-object associations. PMID- 22302646 TI - Rapid, effective, and long-lasting behavioral recovery produced by microsutures, methylene blue, and polyethylene glycol after completely cutting rat sciatic nerves. AB - Behavioral function lost in mammals (including humans) after peripheral nerve severance is slowly (weeks to years) and often poorly restored by 1-2-mm/day, nonspecifically directed outgrowths from proximal axonal stumps. To survive, proximal stumps must quickly repair (seal) plasmalemmal damage. We report that, after complete cut- or crush-severance of rat sciatic nerves, morphological continuity, action potential conduction, and behavioral functions can be consistently (>98% of trials), rapidly (minutes to days), dramatically (70-85% recovery), and chronically restored and some Wallerian degeneration prevented. We assess axoplasmic and axolemmal continuity by intra-axonal dye diffusion and action potential conduction across the lesion site and amount of behavioral recovery by Sciatic Functional Index and Foot Fault tests. We apply well specified sequences of solutions containing FDA-approved chemicals. First, severed axonal ends are opened and resealing is prevented by hypotonic Ca2+-free saline containing antioxidants (especially methylene blue) that inhibit plasmalemmal sealing in sciatic nerves in vivo, ex vivo, and in rat B104 hippocampal cells in vitro. Second, a hypotonic solution of polyethylene glycol (PEG) is applied to open closely apposed (by microsutures, if cut) axonal ends to induce their membranes to flow rapidly into each other (PEG-fusion), consistent with data showing that PEG rapidly seals (PEG-seals) transected neurites of B104 cells, independently of any known endogenous sealing mechanism. Third, Ca2+ containing isotonic saline is applied to induce sealing of any remaining plasmalemmal holes by Ca2+-induced accumulation and fusion of vesicles. These and other data suggest that PEG-sealing is neuroprotective, and our PEG-fusion protocols that repair cut- and crush-severed rat nerves might rapidly translate to clinical procedures. PMID- 22302647 TI - Paradoxical air embolism following contrast material injection through power injectors in patients with a patent foramen ovale. AB - In patients with a patent foramen ovale, use of air filters during intravenous infusions is common, but they are not compatible with power injection. Therefore we aimed to assess the incidence of paradoxical air embolism on CT of the chest and brain following contrast material injection through a power injector in patients with a patent foramen ovale, without the use of a filter. In this IRB approved, HIPAA compliant retrospective study, two independent radiologists reviewed 289 CT scans of the chest (n = 233) and brain (n = 56) for vascular air embolism following contrast material injection through a power injector in 93 subjects (43 men, mean age 66 y) with a known patent foramen ovale. The location and amount of the air were assessed. The medical records were reviewed for embolic symptoms. The prevalence and location of right sided and systemic luminal air were determined and inter-observer agreement for detection of intraluminal vascular air was calculated. Vascular air embolism was observed in 19.3% (56/289) of the studies; small in 52 and moderate in 4. In 42 studies, intravascular air was seen in a single territory and 14 studies had intravascular air in multiple territories. None had air in the left side of the heart or brain to suggest paradoxical air embolism. The inter-observer agreement for detection of vascular air was moderate (k = 0.6). Paradoxical air embolism in patients with a patent foramen ovale following contrast material injection with a power injector is rare. PMID- 22302648 TI - A new quantification method for mechanical dyssynchrony with three-dimensional echocardiography; segmental time and volume loss for prediction of response to cardiac resynchronisation therapy. AB - A novel method to assess left ventricular (LV) mechanical dyssynchrony using three-dimensional echocardiography (3DE) and semi-automated border detection was investigated, which might be superior in prediction of response to cardiac resynchronisation therapy (CRT) compared to traditional measures that rely solely on segmental time-to-contraction. Twenty-eight heart failure patients underwent real-time 3DE before CRT and at 6-12 months follow-up. Analysis of 3DE was performed using TomTec Research-Arena software featuring semi-automated endocardial border detection. The following echocardiographic parameters were calculated in a 16-segment model: areas under segmental time-volume-curves (STV); delay between contraction of the earliest and latest segment (L-E); and standard deviation of segmental time-to-contraction (SDI). Response to CRT was defined as >=10% decrease in LV end-systolic volume at follow-up. Baseline Pre-STV had a higher sensitivity than SDI for prediction of response (94 vs 67%, respectively), with equal specificity (78%) and a higher area under receiver operator characteristic curve. In contrast, L-E had a sensitivity of 83% and a specificity of 56%. Using 3DE, methods that combine segmental time-to-contraction with segmental contractility might improve LV dyssynchrony assessment compared to traditional methods based on segmental time-to-contraction alone. Pre-STV might be a better predictor of response to CRT than SDI. PMID- 22302649 TI - Radiofrequency volumetric tissue reduction of the inferior turbinate in a sheep model. AB - OBJECTIVES/HYPOTHESIS: To validate the sheep model for endoscopic nasal surgery, and to utilize this model to compare the immediate and early postoperative histopathologic effects of four electrosurgical turbinate reduction techniques. STUDY DESIGN: Pilot comparative study of electrosurgical devices for inferior turbinate reduction using a sheep model. METHODS: Three radiofrequency devices (one monopolar and two bipolar) were compared to monopolar electrosurgery in a sheep model of inferior turbinate reduction. Procedures were performed according to device manufacturer guidelines using standard endoscopic instruments. Normative acoustic rhinometry data were obtained for the sheep model. Histopathologic analysis of turbinate specimens was performed at postoperative day 0 and 21. RESULTS: Turbinate reduction was performed on seven sheep, one procedure on each side, yielding 14 turbinate specimens. Acoustic rhinometry was validated in the sheep model and demonstrated increased nasal volumes following decongestion and turbinate reduction. Submucosal destruction of glands and venous sinusoids and replacement with fibrosis were demonstrated as a common mechanism of action for all four electrosurgical devices. Epithelial disruption was seen with all devices on postoperative day 0. Squamous metaplasia and normal respiratory epithelial regeneration were documented variably between devices at postoperative day 21. CONCLUSIONS: The sheep model is useful for study of both the anatomic and histopathologic effects of endonasal procedures. Standard endoscopic instruments and acoustic rhinometry can be used in this model with reproducible results. In this pilot animal study, radiofrequency devices for inferior turbinate reduction demonstrated greater preservation of normal nasal mucosal respiratory epithelium when compared to monopolar electrosurgery. PMID- 22302650 TI - Spatiotemporal image correlation-derived volumetric Doppler impedance indices from spherical samples of the placenta: intraobserver reliability and correlation with conventional umbilical artery Doppler indices. AB - OBJECTIVE: Volumetric impedance indices derived from spatiotemporal image correlation (STIC) power Doppler ultrasound (PDU) might overcome the influence of machine settings and attenuation. We examined the feasibility of obtaining these indices from spherical samples of anterior placentas in healthy pregnancies, and assessed intraobserver reliability and correlation with conventional umbilical artery (UA) impedance indices. METHODS: Uncomplicated singleton pregnancies with anterior placenta were included in the study. A single observer evaluated UA pulsatility index (PI), resistance index (RI) and systolic/diastolic ratio (S/D) and acquired three STIC-PDU datasets from the placenta just above the placental cord insertion. Another observer analyzed the STIC-PDU datasets using Virtual Organ Computer-aided AnaLysis (VOCAL) spherical samples from every frame to determine the vascularization index (VI) and vascularization flow index (VFI); maximum, minimum and average values were used to determine the three volumetric impedance indices (vPI, vRI, vS/D). Intraobserver reliability was examined by intraclass correlation coefficients (ICC) and association between volumetric indices from placenta, and UA Doppler indices were assessed by Pearson's correlation coefficient. RESULTS: A total of 25 pregnant women were evaluated but five were excluded because of artifacts observed during analysis. The reliability of measurement of volumetric indices of both VI and VFI from three STIC-PDU datasets was similar, with all ICCs >= 0.78. Pearson's r values showed a weak and non-significant correlation between UA pulsed-wave Doppler indices and their respective volumetric indices from spherical samples of placenta (all r >= 0.23). VOCAL indices from specific phases of the cardiac cycle showed good repeatability (ICC >= 0.92). CONCLUSION: Volumetric impedance indices determined from spherical samples of placenta are sufficiently reliable but do not correlate with UA Doppler indices in healthy pregnancies. PMID- 22302651 TI - Assessing the effectiveness of a community-based sensitization strategy in creating awareness about HPV, cervical cancer and HPV vaccine among parents in North West Cameroon. AB - In 2010, the Cameroon Baptist Convention Health Services (CBCHS) received a donation of HPV vaccine (Gardasil(r)) to immunize girls of ages 9-13 years in the North West Region of Cameroon. We evaluated the effectiveness of the CBCHS campaign program in sensitizing parents/guardians to encourage HPV vaccine uptake, identified factors that influence parents' decisions to vaccinate girls, and examined the uptake of cervical cancer screening among mothers. We conducted a cross-sectional survey in four healthcare facilities run by CBCHS, churches and other social settings. A total of 350 questionnaires were distributed and 317 were used for the analysis. There were high levels of awareness about cervical cancer, HPV and HPV vaccine. 75.5% understood HPV is sexually transmitted and 90.3% were aware of the use of vaccine as a preventive measure. Effectiveness of the vaccine (31.8%) and side effects/safety (18.4%) were the major barriers for parents to vaccinate their daughters. Bivariate analysis further revealed that the level of education (p = 0.0006), income level (p = 0.0044) and perceived risks (p = 0.0044) are additional factors influencing parents' decisions to vaccinate girls. 35.3% of women had sought a cervical cancer screening, significantly higher than the general estimated rate of screening (<10%) in other parts of Cameroon and sub-Saharan Africa. These results support the viability of a community-tailored sensitization strategy to increase awareness among the targeted audience of parents/guardians, who are critical decision-makers for vaccine delivery to children. PMID- 22302652 TI - Ethnic differences in prevalence and barriers of HBV screening and vaccination among Asian Americans. AB - Our study identifies the prevalence of HBV virus (HBV) screening and vaccination among Asian Americans, and ethnic differences for factors associated with screening and vaccination behaviors. In 2009-2010 we recruited 877 Korean, Chinese, and Vietnamese Americans 18 years of age and above through several community organizations, churches and local ethnic businesses in Maryland for a health education intervention and a self-administered survey. Prevalence of HBV screening, screening result and vaccinations were compared by each ethnic group. We used logistic regression analysis to understand how sociodemographics, familial factors, patient-, provider-, and resource-related barriers are associated with screening and vaccination behaviors, using the total sample and separate analysis for each ethnic group. Forty-seven percent of participants reported that they had received HBV screening and 38% had received vaccinations. Among the three groups, the Chinese participants had the highest screening prevalence, but lowest self-reported infection rate; Vietnamese has the lowest screening and vaccination prevalence. In multivariate analysis, having better knowledge of HBV, and family and physician recommendations was significantly associated with screening and vaccination behaviors. Immigrants who had lived in the US for more than a quarter of their lifetime were less likely to report ever having been screened (OR = 0.39, 95% CI: 0.28-0.55) or vaccinated (OR = 0.62, 95% CI: 0.44-0.88). In ethnic-specific analysis, having a regular physician (OR = 4.46, 95% CI: 1.62-12.25) and doctor's recommendation (OR = 2.11, 95% CI: 1.05 4.22) are significantly associated with Korean's vaccination behaviors. Health insurance was associated with vaccination behaviors only among Vietnamese (OR = 2.66, 95% CI: 1.21-5.83), but not among others. PMID- 22302653 TI - Attitudes toward hepatitis B virus among Vietnamese, Chinese and Korean Americans in the Houston area, Texas. AB - We explored attitudes about prevention, screening and treatment of hepatitis B virus (HBV) infection in Chinese, Korean and Vietnamese communities. We use qualitative methods in 12 focus groups (n = 113) of adults who self-reported their ethnicity to be Chinese, Korean, or Vietnamese. We use grounded theory (i.e., consensus-building between co-coders about recurring, emerging themes) for analysis. Diet, nutrition, fatigue and stress were misidentified as HBV causes. Improving hygiene, diet, exercise, and holistic methods were misidentified as viable HBV prevention methods. Common screening problems included not affording test and not understanding test results. Participants shared reasons for using complementary and alternative medicine--when Western medicine fails or becomes unaffordable. Participants sought information from medical providers and fellow community members, but also from the internet. Many of the attitudes and opinions that emerged may deter participation in HBV screening, prevention and treatment, insofar as community members may factor them into healthcare decision-making, choose alternative but ineffective methods of prevention and treatment, and undervalue the benefits of screening. More patient education in both traditional and new media is necessary for clarifying transmission, screening and treatment misunderstandings. PMID- 22302654 TI - Hyalinizing clear cell adenocarcinoma of the oropharynx. AB - BACKGROUND: Hyalinizing clear cell adenocarcinoma (HCCA) is a rare salivary gland malignancy. To our knowledge, there are no published reports of primary clear cell carcinoma of the vallecula. METHODS: A 59-year-old man with progressive dysphagia and otalgia underwent direct laryngoscopy with biopsy of a vallecular mass. The pathology results returned as clear cell adenocarcinoma. He underwent a wide local excision for his T2N0M0 stage II tumor. RESULTS: Clear cell adenocarcinoma of the oropharynx typically presents as a painless neck mass and it can be difficult to distinguish from other clear cell malignancies. CONCLUSION: Immunohistochemical staining is essential for narrowing the differential diagnosis of these lesions. Treatment is controversial but usually consists of wide local excision and possibly a neck dissection. PMID- 22302655 TI - Operating room traffic is a major concern during total joint arthroplasty. AB - BACKGROUND: Periprosthetic joint infection (PJI) is a challenging complication associated with total joint arthroplasty(TJA). Traffic in the operating room (OR) increases bacterial counts in the OR, andmay lead to increased rates of infection. QUESTION/PURPOSES: Our purposes were to (1) define the incidence of door opening during primary and revision TJA,providing a comparison between the two types of procedures,and (2) identify the causes of door opening in order to develop a strategy to reduce traffic in the operating room. METHODS: An observer collected data during 80 primary and 36 revision TJAs. Surgeries were performed under vertical, laminar flow. Operating room personnel were unaware of the observer, thus removing bias from traffic. The observer documented the number, reason, and personnel involved in the event of a door opening from time of tray opening to closure of the surgical site. RESULTS: The average operating time for primary and revision procedures was 92 and 161 minutes, respectively. Average door openings were 60 in primary cases and 135 in revisions, yielding per minute rates of 0.65 and 0.84, respectively. The circulating nurse and surgical implant representatives constituted the majority of OR traffic. CONCLUSIONS: Traffic in the OR is a major concern during TJA. Revision cases demonstrated a particularly high rate of traffic. Implementation of strategies, such as storage of instruments and components in the operating room and education of OR personnel, is required to reduce door openings in the OR. PMID- 22302656 TI - Anatomic mapping of short external rotators shows the limit of their preservation during total hip arthroplasty. AB - BACKGROUND: The direct anterior approach in THA requires no detachment of muscle insertions. However, damage to the short external rotator muscles may occur when attempting to elevate the femur for exposure. Although the anatomic insertions of these muscles are approximately known, there are no quantitative data regarding their locations. QUESTIONS/PURPOSES: We therefore asked where and how the tendons attach to the inner aspect of the greater trochanter. METHODS: In 20 cadaveric hips we identified the attachments of the short external rotator tendons on the medial aspect of the greater trochanter. Mapping of the attachment site was performed by defining coordinate axes; the total width and height of the greater trochanter represented 100% and distances of the attachment from the anteroinferior reference point were given. RESULTS: The mean anterior border location of the conjoined tendon (obturator internus, gemellus superior, and gemellus inferior) attachment was located at 29% (13 mm from the anteroinferior reference point), its posterior border at 53% (23 mm), its mean superior border at 70% (15 mm), and its mean inferior border at 24% (5 mm). The mean anterior border of the piriformis tendon attachment was located at 57% (25 mm), its mean posterior border at 78% (34 mm), its mean superior border at 64% (17 mm), and its inferior border at 55% (12 mm). There was considerable variation in these attachment sites among individuals. CONCLUSIONS: The insertion of the conjoined tendon extends to the anterosuperior aspect of the greater trochanter. Together with the considerable variation of the attachment site, external rotator muscles remain at risk of being damaged during the capsular release. PMID- 22302657 TI - Value-based healthcare and orthopaedic surgery. PMID- 22302658 TI - Does limb-salvage surgery offer patients better quality of life and functional capacity than amputation? AB - INTRODUCTION: Patients with aggressive lower extremity musculoskeletal tumors may be candidates for either above-knee amputation or limb-salvage surgery. However, the subjective and objective benefits of limb-salvage surgery compared with amputation are not fully clear. QUESTIONS/PURPOSES: We therefore compared functional status and quality of life for patients treated with above-knee amputation versus limb-salvage surgery. METHODS: We reviewed 20 of 51 patients aged 15 years and older treated with above-knee amputation or limb-salvage surgery for aggressive musculoskeletal tumors around the knee between 1994 and 2004 as a retrospective cohort study. At last followup we obtained the Physiological Cost Index, the Reintegration to Normal Living Index, SF-36, and the Toronto Extremity Salvage Score questionnaires. The minimum followup was 12 months (median, 56 months; range, 12-108 months). RESULTS: Compared with patients having above-knee amputation, patients undergoing limb-salvage surgery had superior Physiological Cost Index scores and Reintegration to Normal Living Index. The Toronto Extremity Salvage scores and SF-36 scores were similar in the two groups. CONCLUSION: These data suggest that limb-salvage surgery offers better gait efficiency and return to normal living compared with above-knee amputation, but does not improve the patient's perception of quality of life. PMID- 22302659 TI - The Role of Regulatory T Cells in Mesothelioma. AB - Malignant mesothelioma (MM) appears to be responsive to immunotherapy. The lack of complete tumour cure as a result of many immunotherapies tested to date suggests that the immune response to MM is complex and multi-parametric. Regulatory T (Treg) cells are prevalent within murine and human mesotheliomas with their removal shown to result in tumour growth inhibition and the release of anti-tumour effector T cells from immunosuppression. The targeting of immune checkpoints as treatments for various solid tumours has recently shown promise in clinical settings. In addition, synergy between chemotherapy and immunotherapy has been demonstrated for many cancers, including mesothelioma. Here we demonstrate Treg cells as critical mediators of the anti-tumour immune response to MM and potential targets for anti-tumour immunotherapy; though the timing and dosage of Treg cell manipulating immunotherapies need to be optimised. PMID- 22302661 TI - Soluble ST2 is associated with adverse outcome in patients with heart failure of ischaemic aetiology. AB - AIMS: In patients with ischaemic heart failure (HF), myocardial dysfunction often progresses. Elevated levels of soluble ST2 (sST2) are associated with a poor prognosis, but an association between sST2 and worsening heart failure per se has not been established. We assessed the association between sST2 and cause-specific outcome in 1449 patients enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA study). METHODS AND RESULTS: Soluble ST2 was measured with a highly sensitive immunoassay in 1449 patients >=60 years of age with left ventricular ejection fraction (LVEF) <=40% due to ischaemic heart disease. By Cox regression analyses, we found sST2 to be associated with the primary endpoint, i.e. a composite of cadiovascular (CV) death, non-fatal myocardial infarction, or stroke, as well as all pre-defined secondary endpoints in the CORONA study, even after adjustment for baseline clinical variables. After adjustment for N-terminal pro brain natriuretic peptide and C-reactive protein, the association between sST2 and the primary endpoint was attenuated and no longer statistically significant. However, sST2 remained associated with death due to worsening HF, hospitalization due to worsening HF, and hospitalization due to any CV cause, even after full adjustment. CONCLUSIONS: Soluble ST2 is associated with adverse outcomes in older patients with systolic, ischaemic HF. In particular, sST2 is independently associated with worsening HF. PMID- 22302662 TI - Use of procalcitonin for the diagnosis of pneumonia in patients presenting with a chief complaint of dyspnoea: results from the BACH (Biomarkers in Acute Heart Failure) trial. AB - AIMS: Biomarkers have proven their ability in the evaluation of cardiopulmonary diseases. We investigated the utility of concentrations of the biomarker procalcitonin (PCT) alone and with clinical variables for the diagnosis of pneumonia in patients presenting to emergency departments (EDs) with a chief complaint of shortness of breath. METHODS AND RESULTS: The BACH trial was a prospective, international, study of 1641 patients presenting to EDs with dyspnoea. Blood samples were analysed for PCT and other biomarkers. Relevant clinical data were also captured. Patient outcomes were assessed at 90 days. The diagnosis of pneumonia was made using strictly validated guidelines. A model using PCT was more accurate [area under the curve (AUC) 72.3%] than any other individual clinical variable for the diagnosis of pneumonia in all patients, in those with obstructive lung disease, and in those with acute heart failure (AHF). Combining physician estimates of the probability of pneumonia with PCT values increased the accuracy to >86% for the diagnosis of pneumonia in all patients. Patients with a diagnosis of AHF and an elevated PCT concentration (>0.21 ng/mL) had a worse outcome if not treated with antibiotics (P = 0.046), while patients with low PCT values (<0.05 ng/mL) had a better outcome if they did not receive antibiotic therapy (P = 0.049). CONCLUSION: Procalcitonin may aid in the diagnosis of pneumonia, particularly in cases with high diagnostic uncertainty. Importantly, PCT may aid in the decision to administer antibiotic therapy to patients presenting with AHF in which clinical uncertainty exists regarding a superimposed bacterial infection. PMID- 22302663 TI - Clinical characteristics and outcomes of hospitalized heart failure patients with systolic dysfunction and chronic obstructive pulmonary disease: findings from OPTIMIZE-HF. AB - AIMS: Chronic obstructive pulmonary disease (COPD) is common in heart failure (HF) patients, yet the population is poorly characterized and associated with conflicting outcomes data. We aimed to evaluate the clinical characteristics and outcomes of HF patients with systolic dysfunction and COPD in a large acute HF registry. METHODS AND RESULTS: OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) was a performance-improvement registry of patients hospitalized with HF (n =48 612), which included a pre-specified subgroup of patients (n =5,701) with 60- to 90-day follow-up. We performed a retrospective analysis of the clinical characteristics and outcomes (length of stay, and in-hospital and 60-day mortality) of patients with systolic dysfunction according to baseline COPD status. COPD was present in 25% of the patients. These patients had more co-morbidities compared with patients without COPD. They were less likely to receive a beta-blocker or angiotensin-converting enzyme inhibitor during hospitalization and at discharge (P < 0.001). COPD was associated with an increased median length of stay [5 days (interquartile range 3-8) vs. 4 days (interquartile range 3-7), P < 0.0001] and increased in-hospital all-cause and non-cardiovascular (CV) mortality, with rates of 4.5% vs. 3.7% (P =0.01) and 1.0% vs. 0.6% (P =0.01), respectively, for the two endpoints, but similar 60-day mortality (6.2% vs. 6.0%, P =0.28). After risk adjustment, the in-hospital non-CV mortality remained increased (odds ratio 1.65, 95% confidence interval 1.12-2.41; P =0.01). CONCLUSION: The presence of COPD in HF patients with systolic dysfunction is associated with an increased burden of co-morbidities, lower use of evidence-based HF medications, longer hospitalizations, and increased in-hospital non-CV mortality, but similar post discharge mortality. PMID- 22302664 TI - Isovolemic hemodilution-red cell exchange for prevention of cerebrovascular accident in sickle cell anemia: the standard operating procedure. AB - Red blood cell exchange is an accepted superior therapy to simple chronic transfusion, due to minimal risk of iron overload, for secondary prevention of cerebrovascular accidents in selected patients with sickle cell anemia. Recently, we described our experience of Isovolemic Hemodilution-Red Blood Cell Exchange (IHD-RBCx), a two-step modification of the conventional RBCx with several advantages, including cost reduction. We are describing our standard operating procedure for IHD-RBCx with COBE Spectra apheresis system to make it widely available to the apheresis centers interested in implementing this procedure. PMID- 22302665 TI - Topical corticosteroids applied with a squirt system are more effective than a nasal spray for steroid-dependent olfactory impairment. AB - OBJECTIVES/HYPOTHESIS: Oral corticosteroids may restore conductive olfactory dysfunction that has been defined as steroid-dependent olfactory loss, but the effect may be temporary. This study was designed to evaluate whether applying topical corticosteroids with a squirt system was more effective than using a nasal spray to maintain olfactory improvement following oral corticosteroids. STUDY DESIGN: Prospective randomized trial enrolling 32 patients. METHODS: Patients were enrolled if they had suffered from olfactory dysfunction for more than 3 months, and if their composite scores of odor threshold, discrimination, and identification scores in Sniffin' Sticks olfactory tests increased by more than six points after 1 week of oral corticosteroid treatment. A total of 32 patients were enrolled and randomized into two groups. All patients were treated with topical corticosteroids for 2 months using either the spray or squirt system, respectively. RESULTS: Both measured and self-rated olfactory functions after 1 and 2 months of topical corticosteroid treatment were better in the squirt group than in the spray group. However, 2 months of topical corticosteroid treatment with the squirt system only partially maintained olfactory improvement. CONCLUSIONS: The application of topical corticosteroids with a squirt system was more effective than with a spray in maintaining olfactory improvement with oral corticosteroid treatment. Nevertheless, it only partially maintained the improvement so that topical corticosteroid treatment using a squirt system needs to be combined with intervals of short-term oral corticosteroids to treat steroid dependent olfactory loss while avoiding the side effects of long-term oral corticosteroid use. PMID- 22302666 TI - Multimodality approach for advanced-stage juvenile nasopharyngeal angiofibromas. AB - BACKGROUND: Juvenile nasopharyngeal angiofibromas (JNAs) with significant skull base involvement and intracranial extension are challenging tumors. We evaluated our experience in the treatment of extensive JNAs through resection followed by radiosurgery. METHODS: From 1999 to 2007, 10 advanced JNAs (Andrews grade IV) were treated by primary surgical resection followed by gamma knife radiosurgery of residual tumor. Tumor control and treatment morbidity were evaluated. RESULTS: Six months after radiosurgery and annually thereafter, an imaging study was done that revealed decrement in tumor size in 3 patients and no change in 7 patients, after a 3-year minimum follow-up. Clinically, patients are asymptomatic. CONCLUSION: An efficient strategy in the management of extensive JNAs is the use of a multimodality approach, in which surgical resection is followed by the treatment with radiosurgery in critical locations. These therapeutic schemes are safe and offer long-term tumor control. PMID- 22302667 TI - High-intensity focused ultrasound treatment for twin reversed arterial perfusion sequence. AB - Twin reversed arterial perfusion (TRAP) sequence is a serious complication of monochorionic twin pregnancies, in which arterioarterial anastomoses allow blood flow from a 'pump' fetus to an acardiac fetus via reversed flow in the latter's umbilical artery. Several trial treatments for TRAP sequence have been reported, but all of these have been invasive. We present a case of TRAP sequence in which high-intensity focused ultrasound (HIFU) was applied to the umbilical artery of the anomalous twin at 26 weeks as a non-invasive fetal therapy. The HIFU intensity was set at approximately 2300 W/cm(2) with exposure periods of 10 s. Color Doppler ultrasound showed a decrease in blood supply to the anomalous twin, although complete occlusion of the targeted vessel was not achieved. Delivery was by Cesarean section at 29 weeks' gestation and the pump twin survived, without severe clinical complications at 6 months. PMID- 22302668 TI - Differences in predictors of return to work among long-term sick-listed employees with different self-reported reasons for sick leave. AB - INTRODUCTION: The present study aimed to gain insight in the predictors of full return to work (RTW) among employees on long-term sick leave due to three different self-reported reasons for sick leave: physical, mental or co-morbid physical and mental problems. This knowledge can be used to develop diagnosis specific interventions that promote earlier RTW. METHODS: This prospective cohort study with a two-year follow-up employs a sample of 682 Dutch employees, sick listed for 19 weeks (SD = 1.68), who filled out two questionnaires: at 19 weeks and 2 years after the start of sick leave. The dependent measure was duration until full RTW, the independent measures were cause of sick leave, health characteristics, individual characteristics and work characteristics. RESULTS: Reporting both physical and mental problems as reasons for sick leave was associated with a longer duration until full RTW. Nonparametric Cox survival analysis showed that partial RTW at baseline and lower age were strong predictors of earlier RTW in all three groups, and that RTW self-efficacy predicted earlier RTW in two groups. Other predictors of full RTW varied among groups. CONCLUSIONS: Tailoring for different reasons for sick leave might improve the effects of new interventions because the predictors of full RTW differ among groups. Enhancement of partial RTW and RTW self-efficacy may be relevant components of any intervention, as these were predictors of full RTW in at least two groups. PMID- 22302669 TI - Effect of Cerebellohypothalamic Glutamatergic Projections on Immune Function. AB - Our previous work has shown that lesions of the cerebellar interposed nuclei (IN) suppress immune cell functions. Since there is no direct structural connection between the cerebellum and immune system, we explored the pathway mediating the cerebellar immunomodulation at the profile of cerebellohypothalamic projections to understand this modulation. Anterograde tracing of nerve tracts from the cerebellar IN to the hypothalamus was conducted by injection of anterograde tracer dextran-texas red (dextran-TR) in the cerebellar IN. We observed that dextran-TR-labeled nerve fibers, which were sent by cerebellar IN neurons, traveled in the superior cerebellar peduncle (SCP), crossed in SCP decussation, and entered the hypothalamus. In the hypothalamus, the fibers mostly terminated in the lateral hypothalamic area (LHA). Retrograde tracing by injection of retrograde tracer fluoro-ruby (FR) in the LHA found that FR-labeled neurons appeared in contralateral cerebellar IN. Fluorescent immunohistochemistry for glutamate revealed that many of the FR-labeled neurons were glutamatergic. These results demonstrate a direct glutamatergic projection from the cerebellar IN to the LHA. Reduction of the cerebellohypothalamic glutamatergic projections by microinjection of 6-diazo-5-oxo- L-norleucine (DON), an inhibitor of glutaminase for glutamate synthesis, in bilateral cerebellar IN led to suppression of peripheral lymphocyte number, T lymphocyte proliferation, and serum anti-sheep red blood cell IgM level. But the DON injection in the cerebellar cortex that does not send axons to the hypothalamus did not significantly alter all the immune parameters. These findings suggest that cerebellohypothalamic glutamatergic projection modulates immune function, and that via the pathway, the cerebellum implements its immunoregulatory effect. PMID- 22302672 TI - Should registrars be reporting after-hours CT scans? A calculation of error rate and the influencing factors in South Africa. AB - BACKGROUND: There is a heavy reliance on registrars for after-hours CT reporting with a resultant unavoidable error rate. PURPOSE: To determine the after-hours CT reporting error rate by radiology registrars and influencing factors on this error rate. MATERIAL AND METHODS: A 2-month prospective study was undertaken at two tertiary, level 1 trauma centers in Johannesburg, South Africa. Provisional CT reports issued by the registrar on call were reviewed by a qualified radiologist the following morning and information relating to the number, time and type of reporting errors made as well as the body region scanned, indication for the scan, year of training of the registrar, and workload during the call were recorded and analyzed. RESULTS: A total of 1477 CT scans were performed with an overall error rate of 17.1% and a major error rate of 7.7%. The error rate for 2nd, 3rd, and 4th year registrars was 19.4%, 15.1%, and 14.5%, respectively. A significant difference was found between the error rate in reporting trauma scans (15.8%) compared to non-trauma scans (19.2%) although the difference between emergency scans (16.9%) and elective scans (22.6%) was found to be not significant, a finding likely due to the low number of elective scans performed. Abdominopelvic scans elicited the highest number of errors (33.9%) compared to the other body regions such as head (16.5%) and cervical, thoracic, or lumbar spine (11.7%). Increasing workload resulted in a significant increase in error rate when analyzed with a generalized linear model. There was also a significant difference noted in the time of scan groups which we attributed to a workload effect. Missed findings were the most frequent errors seen (57.3%). CONCLUSION: We found an increasing error rate associated with increasing workload and marked increase in errors with the reporting of abdominopelvic scans. There was a decrease in the error rate when looking an increasing year of training although this there was only found to be significant difference between the 2nd and 3rd year registrars. PMID- 22302673 TI - A new sequence for single-shot diffusion-weighted NMR spectroscopy by the trace of the diffusion tensor. AB - Diffusion-weighted spectroscopy is a unique tool for exploring the intracellular microenvironment in vivo. In living systems, diffusion may be anisotropic, when biological membranes exhibit particular orientation patterns. In this work, a volume selective diffusion-weighted sequence is proposed, allowing single-shot measurement of the trace of the diffusion tensor, which does not depend on tissue anisotropy. With this sequence, the minimal echo time is only three times the diffusion time. In addition, cross-terms between diffusion gradients and other gradients are cancelled out. An adiabatic version, similar to localization by adiabatic selective refocusing sequence, is then derived, providing partial immunity against cross-terms. Proof of concept is performed ex vivo on chicken skeletal muscle by varying tissue orientation and intra-voxel shim. In vivo performance of the sequence is finally illustrated in a U87 glioblastoma mouse model, allowing the measurement of the trace apparent diffusion coefficient for six metabolites, including J-modulated metabolites. Although measurement performed along three separate orthogonal directions would bring similar accuracy on trace apparent diffusion coefficient under ideal conditions, the method described here should be useful for probing intimate properties of the cells with minimal experimental bias. PMID- 22302674 TI - Heat shock protein 27 and p16 immunohistochemistry in cervical intraepithelial neoplasia and squamous cell carcinoma. AB - Heat shock protein 27 (hsp27) is expressed by squamous cell carcinoma of the uterine cervix. Results from an earlier study by our group indicted that hsp27 may be a diagnostic marker for cervical intraepithelial neoplasia (CIN) and carcinoma. p16 expression is known to be elevated in intraepithelial uterine cervical cancer and grades 2 and 3 lesions (CIN2, CIN3), but has also been reported to be negative in 5-20% of cervical cancer and CIN lesions. The aim of our study was to confirm immunohistochemically the expression of hsp27 and p16 in cervical lesions. Formalin-fixed, paraffin-embedded cervical tissue specimens obtained between 2002 and 2010 were investigated for hsp27 and p16 expression. Positive staining was detected for hsp27 in 63% of normal cervical tissues, 47% of CIN1 lesions, 75% of CIN2 lesions, 92% of CIN3 lesions, and 100% of squamous cell carcinomas (SCC); the corresponding rates for p16 positivity were 29, 47, 67, 92, and 75%, respectively. Positive staining for both hsp27 and p16 was observed in 6% of normal cervical tissues and in 19% of CIN1, 18% of CIN2, 85% of CIN3, and 75% of SCC specimens. Hsp27 or p16 positivity had a sensitivity of 95.6 or 84.7% and a specificity of 37.2 or 70.5%, respectively, for the identification of CIN3 or SCC lesions; when both hsp27 and p16 were assessed, both the sensitivity and specificity were improved. In conclusion, both hsp27 and p16 immunohistochemistry is a useful tool for the diagnosis of CIN3 lesions or cervical SCC. PMID- 22302675 TI - What is the Functional Role of N-terminal Transmembrane Helices in the Metabolism Mediated by Liver Microsomal Cytochrome P450 and its Reductase? AB - We sought to clarify on the hitherto unresolved role of N-terminal transmembrane segments (TMS) of cytochrome P450 (CYP) and its' reductase (CPR) in protein interaction/catalysis. TMS analyses show little evolutionary conservation in CYPs. The conserved CPR's TMS poses limited scope for predictable/consistent hetero-recognition with the wide bevy of CYPs' TMS, as evident from preliminary analyses and TMhit server predictions for inter-helical binding. Further, experimentations with four different CPR preparations (preps) and two liver microsomal CYPs (2C9 and 2E1) shows that the hydroxylated product formation rate is not quantitatively correlated to the extent of integrity of the CPR N-terms. Incorporation of cytochrome b (5) in some reactions afforded similar rates while employing either fully intact or partially intact CPR. A survey of literature shows that liver microsomal CYPs function quite well even without the TMS or with significantly altered TMS. These observations negate the hypothesis that N-term TMS of CPR or CYP is obligatory for CYP-CPR interaction and catalysis. Also, in CYP2E1-mediated hydroxylation of para-nitrophenol, the extent of intactness or truncation did not significantly affect the CPR preps' catalytic role at very low or high substrate concentrations. To interpret these results, we draw support from recently published research on reduced nicotinamide adenide dinucleotide phosphate oxidase (Takac et al., J Biol Chem, 286:13304-13313, 2011) and from our pertinent earlier works. We infer that CPR' free TMS segment could alter the diffusible reactive oxygen species' dynamics in the microenvironment, thereby altering the reaction outcome. Based on the evidence, we conclude that TMS merely facilitates "interaction/catalysis" by anchoring the CYP and CPR in the lipid interface. PMID- 22302676 TI - Health care system performance of 27 OECD countries. AB - The article is based on a multidimensional conception of healthcare system performance. Our objectives are to assess the performance of the healthcare systems of 27 Organisation for Economic Co-operation and Development (OECD) countries and to discern the countries' profiles according to the homogeneity of their healthcare systems' levels of performance. The analyses were carried out on data collected from the 27 high-income OECD countries, primarily using the OECD Health Data 2007 database, the World Health Organization 2008 statistics, OECD Health at a Glance and OECD Social Indicators. Each healthcare system's performance was assessed on the basis of the volume of available resources, services produced and health outcomes achieved and efficiency, effectiveness and productivity, thus characterizing the investments made in proportion to the available resources and services produced. Overall performance profiles were constructed taking into account simultaneously the level of all these components. Using multiple clusters analysis, we were able to group the countries into four profiles (satisfactory, promising, weak-polarized and limited) according to the homogeneity of their performance levels. This article offers a broad overview of the performance of these healthcare systems. The results will enable decision makers to know the strengths and weaknesses of their own health care system and also to compare it with those of other countries. PMID- 22302678 TI - Clinical value of endosonography in the assessment of laryngeal cancer. AB - BACKGROUND: Endosonography has been successfully used in staging gastrointestinal cancer, but its value is as yet undetermined in laryngology. METHODS: This prospective study includes 84 patients undergoing microlaryngoscopy for laryngeal cancer. The results of endosonography were compared with those of CT and MRI in the 76 surgical cases. RESULTS: In the assessment of laryngal cancer, endosonography was superior to current imaging techniques, whereas CT and MRI showed similar results (accuracy of 89% vs 77% and 77%, respectively). CONCLUSIONS: This study confirms that endosonography is highly effective in staging laryngeal cancer. Therefore, the latter may constitute a complementary diagnostic tool in these tumors and additionally may assist in choosing an adequate treatment. PMID- 22302679 TI - Effect of age on aldosterone/renin ratio (ARR) and comparison of screening accuracy of ARR plus elevated serum aldosterone concentration for primary aldosteronism screening in different age groups. AB - The serum aldosterone concentration (SAC)/plasma renin activity (PRA) ratio (ARR) is considered a useful screening test in the differential diagnosis of essential hypertension (EH) and primary aldosteronism (PA). The purpose of this study is to investigate the effect of age on ARR and compare the screening accuracy of ARR plus elevated SAC for PA screening in different age groups. Thirty-nine patients with PA, 274 patients with EH, and 153 healthy volunteers were recruited. Blood was sampled for SAC and PRA measuring under keeping upright posture for 1 h. Levels of SAC, PRA, and ARR were compared at different ages range for the respective three groups of subjects. The screening accuracy of ARR plus elevated SAC was compared in different age groups and PA patients served as the same positive subjects. In the EH group, logarithmically transformed ARR (Log-ARR) increased with advancing age and reached its peak in the >= 60 years group; in the normotensives group, Log-ARR reached its peak in the 40-49 years group and slightly declined with advancing age. In the PA group, Log-ARR was not age dependent. Screening accuracy increased when combined index of ARR and SAC was used in the >= 40 years group but not in the <40 years group. Although the number of EH patients with elevated ARR increased with advancing age, but the screening accuracy and cutoff values of ARR were not affected by age. Using the combined index of ARR and SAC increased the screening accuracy for the patients older than 40 years, but not necessary for the patients younger than 40 years. PMID- 22302680 TI - Estrogen suppresses expression of the matrix metalloproteinase inhibitor reversion-inducing cysteine-rich protein with Kazal motifs (RECK) within the mouse uterus. AB - RECK (reversion-inducing cysteine-rich protein with Kazal motifs) is a membrane anchored glycoprotein which regulates MMP2 and MMP9 activity and has been proposed to play a role in embryo implantation while misexpression of RECK has been associated with a variety of carcinomas. Unfortunately, understanding on the steroidal regulation of uterine RECK is lacking. To address this gap in our knowledge, we examined steroidal regulation and cellular expression of Reck mRNA and protein within the mouse uterus in vivo. Uterine Reck mRNA and protein were decreased by estrogen, while progesterone alone had no effect. The estrogen induced down regulation could be partially blocked by progesterone. RECK was localized primarily to luminal and glandular epithelial cells and the level of expression was regulated in a similar fashion as in whole tissue by the steroids. Knock-down of endogenous RECK in human endometrial epithelial and stromal cells resulted in a significant increase in active MMP9 expression but not that of pro MMP9 or MMP2. These studies demonstrate that RECK expression in the mouse uterus is steroidally regulated and that within endometrial epithelial and stromal cells, RECK regulates MMP9, but not MMP2 activity. PMID- 22302681 TI - Biomechanical properties of the mid-shaft femur in middle-aged hypophysectomized rats as assessed by bending test. AB - Both stiffness and strength of bones are thought to be controlled by the "bone mechanostat". Its natural stimuli would be the strains of bone tissue (sensed by osteocytes) that are induced by both gravitational forces (body weight) and contraction of regional muscles. Body weight and muscle mass increase with age. Biomechanical performance of load-bearing bones must adapt to these growth induced changes. Hypophysectomy in the rat slows the rate of body growth. With time, a great difference in body size is established between a hypophysectomized rat and its age-matched control, which makes it difficult to establish the real effect of pituitary ablation on bone biomechanics. The purpose of the present investigation was to compare mid-shaft femoral mechanical properties between hypophysectomized and weight-matched normal rats, which will show similar sizes and thus will be exposed to similar habitual loads. Two groups of 10 female rats each (H and C) were established. H rats were 12-month-old that had been hypophysectomized 11 months before. C rats were 2.5-month-old normals. Right femur mechanical properties were tested in 3-point bending. Structural (load bearing capacity and stiffness), geometric (cross-sectional area, cortical sectional area, and moment of inertia), and material (modulus of elasticity and maximum elastic stress) properties were evaluated. The left femur was ashed for calcium content. Comparisons between parameters were performed by the Student's t test. Average body weight, body length, femur weight, femur length, and gastrocnemius weight were not significantly different between H and C rats. Calcium content in ashes was significantly higher in H than in C rats. Cross sectional area, medullary area, and cross-sectional moment of inertia were higher in C rats, whereas cortical area did not differ between groups. Structural properties (diaphyseal stiffness, elastic limit, and load at fracture) were about four times higher in hypophysectomized rats, as were the bone material stiffness or Young's modulus and the maximal elastic stress (about 7*). The femur obtained from a middle-aged H rat was stronger and stiffer than the femur obtained from a young-adult C rat, both specimens showing similar size and bone mass and almost equal geometric properties. The higher than normal structural properties shown by the hypophysectomized femur were entirely due to changes in the intrinsic properties of the bone; it was thus stronger at the tissue level. The change of the femoral bone tissue was associated with a high mineral content and an unusual high modulus of elasticity and was probably due to a diminished bone and collagen turnover. PMID- 22302682 TI - AlloDerm and DermaMatrix implants for parotidectomy reconstruction: a histologic study in the rat model. AB - BACKGROUND: We analyzed tissue incorporation, immune response, and neovascularization of AlloDerm and DermaMatrix in a rat model of postparotidectomy reconstruction. METHODS: In 8 male Sprague-Dawley rats, 3 dimensionally folded AlloDerm implants were placed in the left postparotidectomy bed and 3 in the anterior dorsum as controls. The same was done for DermaMatrix on the right side and posterior dorsum. Two animals were euthanized at 4, 8, and 12 days. A blinded pathologist assessed the degree of fibroblast proliferation, neovascularization, and inflammation. RESULTS: When compared with the dorsum, DermaMatrix implants in the parotid bed had significantly higher numbers of inflammatory cells at 8 and 12 days (p = .049 and .0046). AlloDerm acted more consistently between the postparotidectomy bed and dorsum. CONCLUSIONS: AlloDerm reacts similarly when comparing the postparotidectomy bed to the dorsum. DermaMatrix induces a more marked inflammatory reaction in the postparotidectomy bed when compared with the dorsum. PMID- 22302683 TI - Uncoupling of RAD51 focus formation and cell survival after replication fork stalling in RAD51D null CHO cells. AB - In vertebrate cells, the five RAD51 paralogs (XRCC2/3 and RAD51B/C/D) enhance the efficiency of homologous recombination repair (HRR). Stalling and breakage of DNA replication forks is a common event, especially in the large genomes of higher eukaryotes. When cells are exposed to agents that arrest DNA replication, such as hydroxyurea or aphidicolin, fork breakage can lead to chromosomal aberrations and cell killing. We assessed the contribution of the HRR protein RAD51D in resistance to killing by replication-associated DSBs. In response to hydroxyurea, the isogenic rad51d null CHO mutant fails to show any indication of HRR initiation, as assessed by induction RAD51 foci, as expected. Surprisingly, these cells have normal resistance to killing by replication inhibition from either hydroxyurea or aphidicolin, but show the expected sensitivity to camptothecin, which also generates replication-dependent DSBs. In contrast, we confirm that the V79 xrcc2 mutant does show increased sensitivity to hydroxyurea under some conditions, which was correlated to its attenuated RAD51 focus response. In response to the PARP1 inhibitor KU58684, rad51d cells, like other HRR mutants, show exquisite sensitivity (>1000-fold), which is also associated with defective RAD51 focus formation. Thus, rad51d cells are broadly deficient in RAD51 focus formation in response to various agents, but this defect is not invariably associated with increased sensitivity. Our results indicate that RAD51 paralogs do not contribute equally to cellular resistance of inhibitors of DNAreplication, and that the RAD51 foci associated with replication inhibition may not be a reliable indicator of cellular resistance to such agents. PMID- 22302684 TI - Increased radioresistance via G12S K-Ras by compensatory upregulation of MAPK and PI3K pathways in epithelial cancer. AB - BACKGROUND: Irradiation-induced signaling via the 2 pathways, Raf-MEK-ERK and PI3K-Akt, is known to be closely associated with a limited response to radiotherapy. In the present study we analyzed the relevance of constitutively active K-Ras for postradiogenic pathway stimulation and the option of coordinated inhibition to overcome these rescue mechanisms. METHODS: We used 2 epithelial tumor cell lines as a model system, one of them harboring a G12S K-Ras mutation. Cells were irradiated and the effect of combined treatment with ionizing radiation and inhibitors on the expression of pERK and pAkt was determined by Western blotting. Additionally, clonogenic assays were performed to functionally analyze survival of the cell lines. RESULTS: Compared with the nonmutated cells we observed the G12S cell line showing a clearly reduced response to inhibitor treatment under irradiation. In the case of pharmacologic inhibition of 1 of the pathways a compensatory upregulation of the second cascade leading to increased clonogenic survival seems feasible. However, there was a good functional response of this cell line to double inhibition with both compounds represented by minimized colony forming ability. The activation of ERK and Akt after irradiation was confirmed in xenotransplants showing elevated postradiogenic protein levels. CONCLUSION: With our data we confirmed our hypothesis of postradiogenic constitutive activation of the 2 pathways both required for Ras-mediated radioresistance in epithelial cells. If this effect should prove itself as a general mechanism in Ras-mutated tumors, application of specific inhibitors to block both cascades in parallel could contribute to enhance radiosensitivity in these types of cancer. PMID- 22302685 TI - A recurrent variant branch of the inferior alveolar nerve: is it unique? AB - The only named branch of the inferior alveolar nerve (IAN) before it enters the mandibular foramen is the mylohyoid nerve. However, several variations have been reported in the literature. In this study, a recurrent variant branch of the IAN arising just below the origin of the mylohyoid nerve was investigated in adult Indian cadavers allotted for dissection to the first year dental students of Government Dental College, Ahmedabad (India). The dissection was performed by the lateral approach to the infratemporal fossa. The nerve was found in 12 of 35 sides (34.3%) and 8 of 18 cadavers (44.4%). Thus, in our study it was not a rare variation of the IAN, where in most cases it innervated the lateral pterygoid muscle. In some cases, it terminated in the lateral pterygoid muscle. In others, it penetrated the muscle to join the anterior or posterior division of the mandibular nerve or its branches; thus, the variant nerve in such cases might be regarded as an additional root of the IAN. Because the concerned primordia of the nerves and muscles migrate extensively during development and growth, alternative routes of migration may bring about variants like the one under study. The variant appeared to be unique in some of its features. It may be a source of neuropathic and referred pain. Failure of the conventional inferior alveolar nerve block anesthesia and the peripheral neurectomy used for the treatment of trigeminal neuralgia may be partly due to the presence of this variation. PMID- 22302686 TI - A zinc-dependent mechanism regulates meiotic progression in mammalian oocytes. AB - Precise coordination of meiotic progression is a critical determinant of an egg's capacity to be fertilized successfully, and zinc has emerged as a key regulatory element in this process. An early manifestation of a regulatory role for this transition metal is the significant increase in total intracellular zinc. This accumulation is essential for meiotic progression beyond telophase I and the establishment of meiotic arrest at metaphase II. The subsequent developmental event, fertilization, induces a rapid expulsion of labile zinc that is a hallmark event in meiotic resumption. In the present study, we show that the zinc fluxes work, in part, by altering the activity of the cytostatic factor (CSF), the cellular activity required for the establishment and maintenance of metaphase II arrest in the mature, unfertilized egg. We propose a model in which zinc exerts concentration-dependent regulation of meiosis through the CSF component EMI2, a zinc-binding protein. Together, the data support the conclusion that zinc itself, through its interaction with EMI2, is a central component of the CSF. PMID- 22302687 TI - Ciliary activity in the oviduct of cycling, pregnant, and muscarinic receptor knockout mice. AB - The transport of the oocyte and the embryo in the oviduct is managed by ciliary beating and muscular contractions. Because nonneuronally produced acetylcholine influences ciliary beating in the trachea via the muscarinic receptors M2 and M3, we supposed that components of the cholinergic system may also modulate ciliary activity in the oviduct. To address this issue, we analyzed the expression profile of muscarinic receptors (CHRMs) in the murine oviduct by RT-PCR and assessed ciliary beat frequency (CBF) and cilia-driven particle transport speed (PTS) on the mucosal surface of opened oviductal segments in correlation with histomorphological investigations. RT-PCR of laser-assisted microdissected epithelium revealed expression of Chrm subtypes Chrm1 and Chrm3. In opened isthmic segments, particle transport was barely seen, correlating with a significantly lower number of ciliated cells compared to the ampulla. In the ampulla, basal PTS and CBF were high (71 MUm/sec and 21 Hz, respectively) both in cycling and pregnant wild-type mice and in mice with targeted deletion of the Chrm genes Chrm1, Chrm3, Chrm4, and Chrm5. In contrast to the trachea, where basal ciliary activity was low and largely enhanced by muscarinic stimulation, muscarinic agonists and antagonists did not affect the high ampullar PTS. Our results imply that this high oviductal autonomous ciliary activity is independent from the intrinsic cholinergic system and serves to maintain optimal clearance of the tube throughout all stages of the estrous cycle and early pregnancy. PMID- 22302688 TI - The industrial chemical bisphenol A (BPA) interferes with proliferative activity and development of steroidogenic capacity in rat Leydig cells. AB - The presence of bisphenol A (BPA) in consumer products has raised concerns about potential adverse effects on reproductive health. Testicular Leydig cells are the predominant source of the male sex steroid hormone testosterone, which supports the male phenotype. The present report describes the effects of developmental exposure of male rats to BPA by gavage of pregnant and lactating Long-Evans dams at 2.5 and 25 MUg/kg body weight from Gestational Day 12 to Day 21 postpartum. This exposure paradigm stimulated Leydig cell division in the prepubertal period and increased Leydig cell numbers in the testes of adult male rats at 90 days. Observations from in vitro experiments confirmed that BPA acts directly as a mitogen in Leydig cells. However, BPA-induced proliferative activity in vivo is possibly mediated by several factors, such as 1) protein kinases (e.g., mitogen activated protein kinases or MAPK), 2) growth factor receptors (e.g., insulin like growth factor 1 receptor-beta and epidermal growth factor receptors), and 3) the Sertoli cell-secreted anti-Mullerian hormone (also called Mullerian inhibiting substance). On the other hand, BPA suppressed protein expression of the luteinizing hormone receptor (LHCGR) and the 17beta-hydroxysteroid dehydrogenase enzyme (HSD17B3), thereby decreasing androgen secretion by Leydig cells. We interpret these findings to mean that the likely impact of deficits in androgen secretion on serum androgen levels following developmental exposure to BPA is alleviated by increased Leydig cell numbers. Nevertheless, the present results reinforce the view that BPA causes biological effects at environmentally relevant exposure levels and its presence in consumer products potentially has implication for public health. PMID- 22302689 TI - Photoperiodic modulation of the suppressive actions of prolactin and dopamine on the pituitary gonadotropin responses to gonadotropin-releasing hormone in sheep. AB - In a variety of species, the LH-secretory response to gonadotropin-releasing hormone (GnRH) is completely suppressed by the combined actions of prolactin (PRL) and dopamine (DA). In sheep, this effect is only observed under long days (nonbreeding season [NBS]). To investigate the level at which these mechanisms operate, we assessed the effects of PRL and bromocriptine (Br), a DA agonist, on the gonadotropin-secretory and mRNA responses to GnRH in pituitary cell cultures throughout the ovine annual reproductive cycle. As expected, the LH-secretory response to GnRH was only abolished during the NBS following combined PRL and Br application. Conversely, the LHB subunit response to GnRH was reduced during both the BS and NBS by the combined treatment and Br alone. Similar results were obtained in pars distalis-only cultures, indicating that the effects are pars tuberalis (PT)- independent. Further signaling studies revealed that PRL and Br alter the LH response to GnRH via convergence at the level of PLC and PKC. Results for FSH generally reflected those for LH, except during the BS where removal of the PT allowed PRL and Br to suppress the FSH-secretory response to GnRH. These data show that suppression of the LH-secretory response to GnRH by PRL and DA is accompanied by changes in mRNA synthesis, and that the photoperiodic modulation of this inhibition operates primarily at the level of LH release through alterations in PKC and PLC. Furthermore, the suppressive effects of PRL and DA on the secretion of FSH are photoperiodically regulated in a PT dependent manner. PMID- 22302691 TI - Tissue remodeling in the female reproductive tract--a complex process becomes more complex: the role of Hox genes. PMID- 22302690 TI - Prenatal testosterone exposure leads to hypertension that is gonadal hormone dependent in adult rat male and female offspring. AB - Prenatal testosterone exposure impacts postnatal reproductive and endocrine function, leading to alterations in sex steroid levels. Because gonadal steroids are key regulators of cardiovascular function, it is possible that alteration in sex steroid hormones may contribute to development of hypertension in prenatally testosterone-exposed adults. The objectives of this study were to evaluate whether prenatal testosterone exposure leads to development of hypertension in adult males and females and to assess the influence of gonadal hormones on arterial pressure in these animals. Offspring of pregnant rats treated with testosterone propionate or its vehicle (controls) were examined. Subsets of male and female offspring were gonadectomized at 7 wk of age, and some offspring from age 7 to 24 wk received hormone replacement, while others did not. Testosterone exposure during prenatal life significantly increased arterial pressure in both male and female adult offspring; however, the effect was greater in males. Prenatal androgen-exposed males and females had more circulating testosterone during adult life, with no change in estradiol levels. Gonadectomy prevented hyperandrogenism and also reversed hypertension in these rats. Testosterone replacement in orchiectomized males restored hypertension, while estradiol replacement in ovariectomized females was without effect. Steroidal changes were associated with defective expression of gonadal steroidogenic genes, with Star, Sf1, and Hsd17b1 upregulation in testes. In ovaries, Star and Cyp11a1 genes were upregulated, while Cyp19 was downregulated. This study showed that prenatal testosterone exposure led to development of gonad-dependent hypertension during adult life. Defective steroidogenesis may contribute in part to the observed steroidal changes. PMID- 22302692 TI - 1,25-dihydroxyvitamin D3 treatment shrinks uterine leiomyoma tumors in the Eker rat model. AB - Uterine leiomyomas (fibroids) are the most common benign tumors in women of reproductive age. These tumors are three to four times more prevalent in African American women, who also have a 10 times higher incidence of hypovitaminosis D than white women. Recent studies have demonstrated the antitumor effects of 1,25 dihydroxyvitamin D3 on several cancers, but its effects on uterine leiomyomas are still unknown. To determine the antitumor and therapeutic effects of 1,25 dihydroxyvitamin D3 on uterine leiomyomas, female Eker rats (14-16 mo old) harboring uterine leiomyomas were randomized into control and experimental groups and were given vehicle versus 1,25-dihydroxyvitamin D3 (0.5 MUg/kg per day) subcutaneously for 3 wk, respectively. At the end of the experiment, the rats were euthanized, and the leiomyoma tumors were analyzed. Treatment with 1,25 dihydroxyvitamin D3 significantly reduced leiomyoma tumor size in Eker rats. It also reduced leiomyoma size by suppressing cell growth and proliferation-related genes (Pcna, cyclin D1 [Ccnd1], Myc, Cdk1, Cdk2, and Cdk4), antiapoptotic genes (Bcl2 and Bcl2l1 [Bcl-x]), and estrogen and progesterone receptors. Additionally, immunohistochemistry revealed decreased expression of PCNA and MKI67 (a marker of proliferation) and increased expression of caspase 3 in 1,25-dihydroxyvitamin D3 treated Eker rat leiomyomas. Toxicity analyses using serum samples showed similar levels of SGOT, SGPT, calcium, and total bilirubin in 1,25-dihydroxyvitamin D3 treated and vehicle-treated control Eker rats. These results support that 1,25 dihydroxyvitamin D3 is an antitumor agent that may be a potential safe, nonsurgical therapeutic option for the treatment of uterine leiomyomas. PMID- 22302693 TI - Measurement and applications of long-range heteronuclear scalar couplings: recent experimental and theoretical developments. AB - The use of long-range heteronuclear couplings, in association with (1)H-(1)H scalar couplings and NOE restraints, has acquired growing importance for the determination of the relative stereochemistry, and structural and conformational information of organic and biological molecules. However, the routine use of such couplings is hindered by the inherent difficulties in their measurement. Prior to the advancement in experimental techniques, both long-range homo- and heteronuclear scalar couplings were not easily accessible, especially for very large molecules. The development of a large number of multidimensional NMR experimental methodologies has alleviated the complications associated with the measurement of couplings of smaller strengths. Subsequent application of these methods and the utilization of determined J-couplings for structure calculations have revolutionized this area of research. Problems in organic, inorganic and biophysical chemistry have also been solved by utilizing the short- and long range heteronuclear couplings. In this minireview, we discuss the advantages and limitations of a number of experimental techniques reported in recent times for the measurement of long-range heteronuclear couplings and a few selected applications of such couplings. This includes the study of medium- to larger sized molecules in a variety of applications, especially in the study of hydrogen bonding in biological systems. The utilization of these couplings in conjunction with theoretical calculations to arrive at conclusions on the hyperconjugation, configurational analysis and the effect of the electronegativity of the substituents is also discussed. PMID- 22302694 TI - Yersinia enterocolitica bacteremia and enterocolitis in a previously healthy 20 month-old girl. AB - Yersinia enterocolitica is a gram-negative bacillus that can cause illness ranging from a self-limiting enterocolitis to life-threatening bacteremia. Y. enterocolitica biotype 1B, serotype O:8 (1B/O:8), is the most pathogenic of the Yersinia species because of the presence of the high-pathogenicity island and the Yersinia virulence plasmid (pYV). Here, we report a pediatric case of Y. enterocolitica 1B/O:8 bacteremia and enterocolitis. A 20-month-old girl was admitted to hospital with fever,pharyngitis, and abdominal pain on day 2. Blood culture on admission was positive for Y. enterocolitica 1B/O:8. Stool culture on day 5 after cefotaxime treatment was also positive for Y. enterocolitica 1B/O:8, but only after cold enrichment at 4 degrees C for 3 weeks. PCR assays identified the pYV only in stool specimens, indicating that strains from routine blood culture at 37 degrees C lacked the pYV. The present case showed the usefulness of stool culture with cold enrichment and agglutination test for the diagnosis of Y. enterocolitica infection. We would therefore like to emphasize the importance of collection and preservation of stool specimens for the identification of pYV. To our knowledge, this is the first reported pediatric case of Y. enterocolitica 1B/O:8 bacteremia. PMID- 22302695 TI - Should urologists care for the pharyngeal infection of Neisseria gonorrhoeae or Chlamydia trachomatis when we treat male urethritis? AB - Detection of Neisseria gonorrhoeae (NG) or Chlamydia trachomatis (CT) from the pharynx of women or men is not uncommon. However, there is no recommendation how urologists should care for the pharyngeal infection of men with urethritis in Japan. The aim of this study is to clarify the prevalence of NG or CT infection in the pharynx of men and to show a recommendation for urologists. The Japanese reports about the detection of NG or CT from the pharynx or the oral cavity of men in Japan are reviewed in the literature from 1990 to 2011. The prevalence of NG or CT in the pharynx was 4% or 6% in men who attended clinics, and 20% or 6% in men who were positive for NG or CT from genital specimens, respectively. Single 1-g dose ceftriaxone was recommended to treat pharyngeal NG, but no evidence was found for pharyngeal CT. There was not enough evidence for recommendation. However, when men with urethritis only caused by NG or CT are treated through the guideline of the Japanese Society of Sexually Transmitted Infection, we do not think additional tests or treatment for the pharynx are needed when a single 1-g dose ceftriaxone for gonococcal urethritis or a single 1 or 2- g dose azithromycin is prescribed for chlamydial urethritis in Japan. PMID- 22302696 TI - Antimicrobial susceptibility and genetic characteristics of Haemophilus influenzae isolated from community-acquired respiratory tract infection patients in Shanghai City, China. AB - Haemophilus influenzae is an important causative pathogen of community-acquired respiratory infection in China. In this study we investigated 37 H. influenzae strains isolated from patients with community-acquired respiratory tract infections (CARTI) in Shanghai city between Dec 2008 and Apr 2009. H. influenzae clinical isolates were identified, and b-lactamase production tests were conducted and minimal inhibitory concentrations(MIC) were measured. Pulsed-field gel electrophoresis(PFGE) was introduced as an effective finger printing method. Two isolates (5.4%) were verified as serotype b strains, and 30 strains (81.1%) were nontypeable H. influenzae. Furthermore, 10 (27.0%) were b-lactamase producing ampicillin-resistance (BLPAR) (TEM-1 type)strains, 11 (29.8%) were low b-lactamase-nonproducing ampicillin-resistant H. influenzae (Low-BLNAR) strains,and the rest were b-lactamase-negative ampicillin-susceptible(BLNAS) strains. Minimum inhibitory concentrations(MIC90; lg/ml) were 2 for ampicillin/sulbactam, 0.05 force fotaxime, 16 for cefaclor, 2 for azithromycin, 0.12 for levofloxacin, and 4 for imipenem. Fingerprint typing by PFGE revealed 23 independent patterns for the isolates. Pattern A (defined in this study) was predominant in BLPAR strains, and a variety of other patterns were detected in Low-BLNAR and BLNAS strains. Although the incidence of ampicillin resistant H. influenzae is increasing in CARTI patients in China, current antimicrobial chemotherapy seems to be effective. PMID- 22302697 TI - Managing major data of genetically modified mice: from scientific demands to legal obligations. AB - The number of genetically modified mice is increasing rapidly. Several limitations when working with these animals are to be considered: small colonies, the continued danger of loss, often a limited breeding-success, the need to keep those mutants in stock, difficult and costly import-procedures, and also a major (scientific) value of those mutants often available only with major restrictions. To gather relevant information about all active and archived genetically modified mouse lines available in-house (>1.500) and to deal with a unique resource for several, quite different purposes, a data base was developed enabling optimum knowledge management and easy access. The data base covers also legal restraints and is being linked with the institutional publication repository. To identify the lines available detailed information is provided for each line, as the international designation, a short name, the characterization/description, and the genetic modification including the technique used therefore. The origin of the mutation (gene-ID# and donor organism), the origin of regulatory elements and their donors are listed as well as the genetic background, back-cross generation, phenotype, possible publications, keywords, and some in-house information. Also aspects of animal welfare, obligations to record genetically modified organisms, and technology transfer are displayed; the latter to make licenses possible (if legally permitted). Material transfer agreements, patents, or legal restrictions are listed. This data base helps to avoid double-imports, saves animals and costs since a redundant generation or import can be omitted. However, this is a contribution to the 3R principles developed by Russell and Burch. PMID- 22302698 TI - Mediastinal goiter presenting with ventricular tachycardia. AB - BACKGROUND: We report a rare case of a mediastinal goiter confined to the thoracic inlet and cavity presenting with ventricular tachycardia as the sole clinical manifestation. METHODS AND RESULTS: The patient did not have any of the typical features of a mediastinal goiter such as neck swelling, dysphagia, or respiratory difficulty, but instead had spontaneous onset of wide-complex tachycardia requiring emergency treatment. This atypical presentation led to initial misinterpretation of imaging studies and delayed diagnosis of the mediastinal mass. The large, completely intrathoracic thyroid goiter abutted the cardiac muscle and required a combined transcervical and median sternotomy approach for removal. The arrhythmia resolved postoperatively. CONCLUSION: To our knowledge, this case represents the first documented presentation of ventricular tachycardia as a unique and sole feature of mediastinal goiter. PMID- 22302699 TI - Dextrocardia, atrial septal defect, severe developmental delay, facial anomalies, and supernumerary ribs in a child with a complex unbalanced 8;22 translocation including partial 8p duplication. AB - We report on a child with dextrocardia, atrial septal defect (ASD), severe developmental delay, hypotonia, 13 pairs of ribs, left preauricular choristoma, hirsutism, and craniofacial abnormalities. Prenatal cytogenetic evaluation showed karyotype 46,XY,?dup(8p)ish del(8)pter. Postnatal array CGH demonstrated a 6.8 Mb terminal deletion at 8p23.3-p23, an interstitial 31.1 Mb duplication within 8p23.1-p11, and a terminal duplication of 0.24 Mb at 22q13.33, refining the karyotype to 46,XY,der(8)dup(8)(p23.1p11.1)t(8;22)(p23.1;q13.1).ish der(8)dup(8)(p23.1p11.1)t(8;22)(p23.1;q13.1) (D8S504-,MS607 + ,ARSA + ,D8Z1 + , RP115713 + +). Previous reports of distal 8p deletion, 8p duplication, and distal 22q duplication have shown similar manifestations, including congenital heart disease, intellectual impairment, and multiple minor anomalies. We correlate the patient's clinical findings with these particular areas of copy number. This case study supports the use of aCGH to identify subtle chromosomal rearrangement in infants with cardiac malformation as their most significant or only apparent birth defect. Additionally, it illustrates why aCGH is essential in the description of chromosome rearrangements, even those seemingly visible via routine karyotype. This method shows that there is often greater complexity submicroscopically, essential to an adequate understanding of a patient's genotype and phenotype. PMID- 22302700 TI - Compatibility of the HINTEGRA prostheses with Korean ankles as evaluated on the basis of cadaveric measurements. AB - The purpose of this study was to obtain anatomical measurements of the distal tibia and talus of Korean ankles and to evaluate, based on those measurements, the compatibility of the HINTEGRA prostheses in the context of total ankle replacement (TAR). We measured the length, width, height, and angles of the distal tibia and talus of 51 cadavers and compared these measurements with the corresponding dimensions of the HINTEGRA prostheses. The male ankles were larger than the female ones as was expected, but their overall shapes did not differ, which fact validates use of the prostheses irrespective of patients' sex. The dimensions of the talus itself did not differ significantly from those previously reported for American whites and blacks and South African whites. This might suggest a possibility that the HINTEGRA prostheses, being used in these countries, would be compatible to Korean ankles, too. In fact, the length range of the talar components was generally compatible with those derived from cadaveric measurements of the trochlea. However, the widths of the tibial and talar components were not completely compatible to Korean ankles. Above all, the length of the large-sized tibial components was much longer than the largest ankles, which would confine the choice of prosthesis mainly to small-sized ones for arthroplasty in Korea. Even though these prostheses are currently used, some modifications are needed to extend their usability in Korea, such as shortening and width/length ratio adjustment of the tibial component, and of the talar component accordingly. PMID- 22302701 TI - Probing the chemical functionalization of single-walled carbon nanotubes with multiple carbon ad-dimer defects. AB - Drying-tube-shaped single-walled carbon nanotubes (SWCNTs) with multiple carbon ad-dimer (CD) defects are obtained from armchair (n,n,m) SWCNTs (n=4, 5, 6, 7, 8; m=7, 13). According to the isolated-pentagon rule (IPR) the drying-tube-shaped SWCNTs are unstable non-IPR species, and their hydrogenated, fluorinated, and chlorinated derivatives are investigated. Interestingly, chemisorptions of hydrogen, fluorine, and chlorine atoms on the drying tube-shaped SWCNTs are exothermic processes. Compared to the reaction energies for binding of H, F, and Cl atoms to perfect and Stone-Wales-defective armchair (5,5) nanotubes, binding of F with the multiply CD defective SWCNTs is stronger than with perfect and Stone-Wales-defective nanotubes. The reaction energy for per F(2) addition is between 85 and 88 kcal mol(-1) more negative than that per H(2) addition. Electronic structure analysis of their energy gaps shows that the CD defects have a tendency to decrease the energy gap from 1.98-2.52 to 0.80-1.17 eV. After hydrogenation, fluorination, and chlorination, the energy gaps of the drying-tube shaped SWCNTs with multiple CD defects are substantially increased to 1.65-3.85 eV. Furthermore, analyses of thermodynamic stability and nucleus-independent chemical shifts (NICS) are performed to analyze the stability of these molecules. PMID- 22302702 TI - Consanguinity and occurrence of cleft lip/palate: a hospital-based registry study in Riyadh. AB - This paper focuses on the influence of consanguinity on the occurrence of orofacial clefts. All patients with orofacial clefts registered at King Faisal Specialist Hospital and Research Center, Riyadh since June 1999 until December 2009 were included in this study. Patients were classified in two distinct groups: cleft lip with or without cleft palate (CL +/- P) and isolated cleft palate (CP). Chi-squared test was used to test independence of variables. Intracluster correlation coefficient was estimated to assess the degree of concordance between siblings. Among 1,171 total patients, CL +/- P was found to be more common (64.0%). Males were more likely to be affected with CL +/- P (M:F = 1.5:1) and females were more likely to be affected with CP (M:F = 0.9:1; P < 0.0001). About a third of patients had a family history of clefts; family history was more likely to be positive for patients with CL +/- P than for patients with CP (33.6% vs. 22.0%; P < 0.0001). Consanguineous relationships were seen in 56.8% of our patients' parents. Family history was more likely to be positive for patients whose parents were consanguineous than those who were non-consanguineous (34.2% vs. 25.8%; P = 0.003), both for the CL +/- P and CP groups. Recurrence among siblings did not differ between those born to consanguineous versus non consanguineous parents. Recurrence of clefts in offspring was higher among parents affected by cleft compared to those who were not affected (51.4% vs. 11.4%; P < 0.0001), both for CL +/- P and CP groups. Education about anticipated genetic consequences of consanguinity is important for populations with a high degree of consanguinity. PMID- 22302703 TI - Effect of management on reproductive performances of the Achai cattle in the Hindu Kush (Northern Pakistan). AB - This study evaluates the effect of management on the undocumented Achai cattle reproductive performance in transhumant farming systems (TFS) and in sedentary farming systems (SFS) in northwestern Pakistan. Data were collected from 172 households in TFS and 270 households in SFS to analyze the effect of farming systems, parity, and calving season on key reproductive traits. The results show that farming systems significantly affect pubertal age, while parity has no significant effect on any of the key traits. The calving season significantly affects the postpartum anoestrus interval in TFS only. More than 50% of the cows in both systems have postpartum anoestrus intervals and calving intervals within the recommended values for cows in tropical countries. Achai cows have high first service conception rates (70% and 71% for TFS and SFS, respectively) and require a relatively small number of services per conception (1.53 +/- 0.06 and 1.48 +/- 0.05 SE for TFS and SFS, respectively). This local breed thus warrants conservation under both farming systems. PMID- 22302704 TI - Antiviral activity of crude extracts from Commiphora swynnertonii against Newcastle disease virus in ovo. AB - Studies were carried out to investigate the effect of crude extracts from resin, leaves, stem barks and root barks of Commiphora swynnertonii against Newcastle disease virus (NDV) using an in ovo assay. Nine-day-old embryonated chicken eggs were divided into seven groups (n = 6) and received various treatments. Six groups were inoculated with velogenic NDV strain; five groups out of these were treated with different concentrations of the four extracts or a diluent, dimethylsulphoxide. The uninoculated and inoculated groups were left as negative and positive controls, respectively. Embryo survival was observed daily and embryo weights were measured day 5 post-inoculation; a few eggs from selected groups were left to hatch. Allantoic fluid from treated eggs and serum from hatched chicks were collected for hemagglutination and hemagglutination inhibition (HI) tests to detect NDV in the eggs and antibodies against NDV in the hatched chicks respectively. Results showed that embryo survival and mean embryo weight were significantly higher (p < 0.001) in those groups which were treated with the crude extracts from C. swynnertonii than the positive control group. Also the extracts significantly (p < 0.001) reduced virus titres, whereas no viruses were detected in the allantoic fluids of the resin-treated group at the highest concentration of 500 MUg/mL. Furthermore, the HI test results showed very low levels of antibodies against NDV in chicks hatched from resin and root bark extract-treated eggs suggesting that these plant materials were capable of destroying the NDV before stimulating the developing chick's immunity. The current findings have clearly demonstrated that crude extracts especially that of resin from C. swynnertonii have strong antiviral activity against NDV in ovo. In vivo trials are needed to validate the use of resin from the tree in controlling Newcastle disease in chickens. PMID- 22302705 TI - Two-photon continuous flow lithography. AB - A new approach for microfluidics-based production of polymeric particles, namely two-photon continuous flow lithography, is reported. This technique takes advantage of two-photon lithography to create objects with sub-micrometer and 3D features, and overcomes the traditional process limitations of two-photon lithography by using multiple beam production under continuous flow. Polymeric fibers, helical and bow-tie particles with sub-diffraction resolution and surface roughness as low as 10 nm are demonstrated. PMID- 22302706 TI - Contribution of germline mutations to PARK2 gene inactivation in lung adenocarcinoma. AB - Homozygous germline mutations of the PARK2 gene are responsible for the development of early-onset Parkinson's disease (PD). Homozygous PARK2 mutations have been also detected in lung adenocarcinoma (LADC). However, since heterozygous PARK2 germline mutations are present in a subset of non-PD individuals, the timing for the occurrence of two-hit PARK2 mutations in LADC progression is unclear. Therefore, we comprehensively analyzed mutations, expression and copy number variations of the PARK2 gene in 267 primary LADCs together with the corresponding noncancerous lung cells and 39 LADC cell lines. Heterozygous germline exonic deletions were detected in five patients with LADC, and loss of heterozygosity including the PARK2 locus was detected in 31/267 (11.6%) LADCs. However, homozygous PARK2 inactivation was not detected in any of them, including the five patients with germline mutations. Homozygous PARK2 inactivation was detected in 6/39 (15%) cell lines, two exonic deletions, one exonic duplication, and three point mutations, while heterozygous PARK2 inactivation was detected in two cell lines (both by exonic deletions). These results strongly indicate that somatic PARK2 mutations occur rarely (or do not occur) in LADC development and that germline PARK2 mutations could contribute to LADC progression but not to LADC development. PMID- 22302707 TI - Suitability of epididymal and testicular ultrasonography and computerized image analysis for assessment of current and future semen quality in the ram. AB - Breeding soundness evaluation (BSE) is the primary assessment for determining the reproductive potential of male animals. This method, however, cannot be used to evaluate semen frequently or to predict future semen quality. Computerized analysis of ultrasonographic images provides information on histophysiological changes in male reproductive organs. We hypothesized that: (i) semen parameters would correlate with ultrasonographic characteristics of the distal region (cauda) of the epididymis and (ii) testicular ultrasound images and/or circulating testosterone concentration would predict future semen quality in the ram. Six adult rams underwent BSE and scrotal ultrasonography approximately 60 d apart (average duration of the spermatogenic cycle) both during the breeding (December and February) and non-breeding (June and August) seasons. An inverse correlation was found between pixel intensity (numerical pixel values) of the epididymes and percentage of sperm in semen with normal morphology (r = -0.46, P < 0.05). Pixel heterogeneity (standard deviation of pixel values) correlated negatively with percentage of sperm with normal morphology (r = -0.42, P < 0.05) and directly with percentage of spermatozoa with abnormal tails (r = 0.43, P < 0.05). Pixel heterogeneity of testicular parenchyma obtained approximately 60 d prior to semen evaluation inversely correlated with percentage of sperm with normal morphology (r = -0.73, P < 0.01) and sperm progressive motility (r = 0.76, P < 0.01), and directly with percentage of sperm with abnormal tails (r = 0.72, P < 0.01) and loose heads (r = 0.79, P < 0.01). We concluded that scrotal ultrasonography combined with computer-assisted analyses of epididymal and testicular echotexture in the ram was a valuable method for determining certain current and future semen parameters, respectively. PMID- 22302708 TI - Chitosan oligosaccharides promote reverse cholesterol transport and expression of scavenger receptor BI and CYP7A1 in mice. AB - Chitosan oligosaccharides (COS) are beneficial in improving plasma lipids and diminishing atherosclerotic risks. In this study, we examined the effects of COS on reverse cholesterol transport (RCT) in C57BL/6 mice. (3)H-cholesterol-laden macrophages were injected intraperitoneally into mice fed with various dosage of COS (250, 500, 1000 mg/kg mouse weight, respectively) or vehicle by gastric gavages. Plasma lipid level was determined and (3)H-cholesterol was traced in plasma, liver, bile and feces. The effects of COS on hepatic cholesterol 7 alpha hydroxylase (CYP7A1) and scavenger receptor BI (SR-BI) expression were also investigated. COS administration led to a significant decrease in plasma total cholesterol and low-density lipoprotein (LDL) cholesterol and a significant increase in peritoneal macrophage-derived (3)H-cholesterol in liver and bile as well as in feces. Liver protein expressions of CYP7A1, SR-BI and LDL receptor (LDL-R) were improved in a dosage-dependent manner in COS-administered mice. Our findings provide the first in vivo demonstration of a positive role for COS in RCT pathway and hepatic CYP7A1 and SR-BI expression in mice. Additionally, the LDL cholesterol lowering effect might be relative to hepatic LDL-R expression stimulated by COS in mice. PMID- 22302709 TI - Role of myocyte enhancing factor 2B in epithelial myofibroblast transition of human gingival keratinocytes. AB - It has recently emerged that the myogenic contribution of the epithelial mesenchymal transition plays a role in neoplastic invasion and metastasis. Myocyte enhancing factor 2B (MEF2B) is the only MEF2 isoform expressed during early embryonic development, and is herein proposed to transactivate the downstream target proteins of the epithelial myofibroblast transition (EMyT). We have previously generated eight preneoplastic cell lines with spindle and cobblestone morphology from human gingival mucosal keratinocytes immortalized by E6/E7 of human papillomavirus type 16. Spindle cells formed tubulogenic morphogenesis on Matrigel and exhibited contractility, anchorage-independent growth and invasiveness to a greater extent than cobblestone cells. Expression of MEF2B mRNA and myofibroblast proteins was higher in spindle cells compared with cobblestone cells. Epidermal growth factor (EGF) treatment of cobblestone cells also induced expression of these genes. Knockdown of MEF2B in a cobblestone cell line abolished EGF-induced upregulation of MEF2, vimentin and non-muscle caldesmon proteins, but enhanced basal expression of mesenchymal vimentin and fibronectin. Differential regulation of intermediate filaments revealed an unrecognized role of MEF2B in myogenic transformation of the epithelial to a myofibroblast phenotype, which occurs as epithelioid variants in some soft tissue sarcomas. PMID- 22302710 TI - Epinephrine-dependent control of glucose metabolism in white adipose tissue: the role of alpha- and beta-adrenergic signalling. AB - Epinephrine controls many important and sometimes opposite processes. This pleiotropic effect is achieved via coupling to different receptor/effector systems. In epididymal white adipose tissue (EWAT) of Wistar rats, we showed that epinephrine stimulated protein kinase B (PKB) phosphorylation on Ser(473). Epinephrine further increased the glucose incorporation into glyceride-glycerol without decreasing glucose availability for other metabolic pathways (i.e. lactate production). Wortmannin (phosphatidylinositol 3-kinase inhibitor) treatment significantly decreased glucose incorporation into glyceride-glycerol and elevated the epinephrine-induced release of free fatty acids (FFA) from the adipose tissue without any change in the intensity of lipolysis measured as glycerol release. Using specific cyclic adenosine monophosphate (cAMP) analogs we demonstrated that cAMP-protein kinase A (PKA) signalling resulted in a strong PKB dephosphorylation and significantly lowered the glucose availability in EWAT. Specific activation of the Epac (exchange protein activated by cAMP)-dependent pathway had only a moderately negative effect on PKB phosphorylation and glucose metabolism. In contrast, alpha(1) agonist methoxamine increased PKB phosphorylation and lactate production. This effect of methoxamine was additive to the effect of insulin and it was abolished by wortmannin treatment. In EWAT of spontaneously dyslipidemic hereditary hypertriglyceridemic (HHTg) rats, we demonstrated significantly lower epinephrine-induced glucose utilization but higher sensitivity to its lipolytic effect. We conclude that in EWAT, epinephrine controls two opposite processes (FFA release and FFA retention) via two different effector systems. The impairment of alpha(1)-dependent, epinephrine-stimulated, glycolysis-dependent FFA esterification may contribute to the establishment of dyslipidemia in insulin resistance. PMID- 22302711 TI - The antioxidant enzyme peroxiredoxin and its protective role in neurological disorders. AB - Peroxiredoxin (Prx) represents a family of sulfhydryl-dependent peroxidases that reduce hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. There are six known mammalian isozymes (Prx1-6), classified as typical 2-Cys, atypical 2-Cys, or 1-Cys Prxs. In addition to their well established peroxide-scavenging activity, Prxs also participate in the regulation of various cell signaling pathways. Experimental studies provide substantial evidence for a protective role of Prxs in various neurological disorders involving oxidative and inflammatory stress. There is also evidence suggesting a potential benefit of Prxs in certain neurological diseases in human subjects. This review first describes the biochemical properties and molecular regulation of Prxs, then summarizes the major findings on the neuroprotective functions of Prxs and finally discusses the feasibility of using natural compounds, including those from herbal remedies to augment Prx expression to counteract oxidative neurological disorders. PMID- 22302712 TI - DNA methylation in plants: relationship to small RNAs and histone modifications, and functions in transposon inactivation. AB - DNA methylation is a type of epigenetic marking that strongly influences chromatin structure and gene expression in plants and mammals. Over the past decade, DNA methylation has been intensively investigated in order to elucidate its control mechanisms. These studies have shown that small RNAs are involved in the induction of DNA methylation, that there is a relationship between DNA methylation and histone methylation, and that the base excision repair pathway has an important role in DNA demethylation. Some aspects of DNA methylation have also been shown to be shared with mammals, suggesting that the regulatory pathways are, in part at least, evolutionarily conserved. Considerable progress has been made in elucidating the mechanisms that control DNA methylation; however, many aspects of the mechanisms that read the information encoded by DNA methylation and mediate this into downstream regulation remain uncertain, although some candidate proteins have been identified. DNA methylation has a vital role in the inactivation of transposons, suggesting that DNA methylation is a key factor in the evolution and adaptation of plants. PMID- 22302713 TI - Metabolic engineering of the Chl d-dominated cyanobacterium Acaryochloris marina: production of a novel Chl species by the introduction of the chlorophyllide a oxygenase gene. AB - In oxygenic photosynthetic organisms, the properties of photosynthetic reaction systems primarily depend on the Chl species used. Acquisition of new Chl species with unique optical properties may have enabled photosynthetic organisms to adapt to various light environments. The artificial production of a new Chl species in an existing photosynthetic organism by metabolic engineering provides a model system to investigate how an organism responds to a newly acquired pigment. In the current study, we established a transformation system for a Chl d-dominated cyanobacterium, Acaryochloris marina, for the first time. The expression vector (constructed from a broad-host-range plasmid) was introduced into A. marina by conjugal gene transfer. The introduction of a gene for chlorophyllide a oxygenase, which is responsible for Chl b biosynthesis, into A. marina resulted in a transformant that synthesized a novel Chl species instead of Chl b. The content of the novel Chl in the transformant was approximately 10% of the total Chl, but the level of Chl a, another Chl in A. marina, did not change. The chemical structure of the novel Chl was determined to be [7-formyl]-Chl d(P) by mass spectrometry and nuclear magnetic resonance spectroscopy. [7-Formyl]-Chl d(P) is hypothesized to be produced by the combined action of chlorophyllide a oxygenase and enzyme(s) involved in Chl d biosynthesis. These results demonstrate the flexibility of the Chl biosynthetic pathway for the production of novel Chl species, indicating that a new organism with a novel Chl might be discovered in the future. PMID- 22302714 TI - Unique properties vs. common themes: the atypical cyanobacterium Gloeobacter violaceus PCC 7421 is capable of state transitions and blue-light-induced fluorescence quenching. AB - The atypical unicellular cyanobacterium Gloeobacter violaceus PCC 7421, which diverged very early during the evolution of cyanobacteria, can be regarded as a key organism for understanding many structural, functional, regulatory and evolutionary aspects of oxygenic photosynthesis. In the present work, the performance of two basic photosynthetic adaptation/protection mechanisms, common to all other oxygenic photoautrophs, had been challenged in this ancient cyanobacterium which lacks thylakoid membranes: state transitions and non photochemical fluorescence quenching. Both low temperature fluorescence spectra and room temperature fluorescence transients show that G. violaceus is capable of performing state transitions similar to evolutionarily more recent cyanobacteria, being in state 2 in darkness and in state 1 upon illumination by weak blue or far red light. Compared with state 2, variable fluorescence yield in state 1 is strongly enhanced (almost 80%), while the functional absorption cross-section of PSII is only increased by 8%. In contrast to weak blue light, which enhances fluorescence yield via state 1 formation, strong blue light reversibly quenches Chl fluorescence in G. violaceus. This strongly suggests regulated heat dissipation which is triggered by the orange carotenoid protein whose presence was directly proven by immunoblotting and mass spectrometry in this primordial cyanobacterium. The results are discussed in the framework of cyanobacterial evolution. PMID- 22302715 TI - Defining a polymethine dye for fluorescence anisotropy applications in the near infrared spectral range. AB - Fluorescence anisotropy in the near-infrared (NIR) spectral range is challenging because of the lack of appropriate NIR fluorescent labels. We have evaluated polymethine fluorescent dyes to identify a leading candidate for NIR anisotropy applications. The NIR dye LS601 demonstrated low fluorescence anisotropy values (r) as a result of its relatively long fluorescent lifetime 1.3 ns. The r value of LS601 unbound and coupled to biological macromolecules was found to have a sufficient dynamic range from 0.24 to 0.37, demonstrating the feasibility of fluorescence anisotropy in the NIR. The viability of fluorescence anisotropy using a NIR label was demonstrated by characterization of dye-protein conjugates. These results open the door to a number of applications in drug discovery, fluorescence anisotropy imaging and contrast agent development. PMID- 22302716 TI - A small terminal deletion 11q in a boy without Jacobsen syndrome: narrowing the critical region for the 11q Jacobsen syndrome phenotype. PMID- 22302717 TI - The microRNAs, MiR-31 and MiR-375, as candidate markers in Barrett's esophageal carcinogenesis. AB - There is a critical need to identify molecular markers that can reliably aid in stratifying esophageal adenocarcinoma (EAC) risk in patients with Barrett's esophagus. MicroRNAs (miRNA/miR) are one such class of biomolecules. In the present cross-sectional study, we characterized miRNA alterations in progressive stages of neoplastic development, i.e., metaplasia-dysplasia-adenocarcinoma, with an aim to identify candidate miRNAs potentially associated with progression. Using next generation sequencing (NGS) as an agnostic discovery platform, followed by quantitative real-time PCR (qPCR) validation in a total of 20 EACs, we identified 26 miRNAs that are highly and frequently deregulated in EACs (>= 4 fold in >50% of cases) when compared to paired normal esophageal squamous (nSQ) tissue. We then assessed the 26 EAC-derived miRNAs in laser microdissected biopsy pairs of Barrett's metaplasia (BM)/nSQ (n = 15), and high-grade dysplasia (HGD)/nSQ (n = 14) by qPCR, to map the timing of deregulation during progression from BM to HGD and to EAC. We found that 23 of the 26 candidate miRNAs were deregulated at the earliest step, BM, and therefore noninformative as molecular markers of progression. Two miRNAs, miR-31 and -31*, however, showed frequent downregulation only in HGD and EAC cases suggesting association with transition from BM to HGD. A third miRNA, miR-375, showed marked downregulation exclusively in EACs and in none of the BM or HGD lesions, suggesting its association with progression to invasive carcinoma. Taken together, we propose miR-31 and -375 as novel candidate microRNAs specifically associated with early- and late-stage malignant progression, respectively, in Barrett's esophagus. PMID- 22302718 TI - Vascular endothelial growth factor in malignant and benign pericardial effusion. AB - BACKGROUND: The pathogenetic role of vascular endothelial growth factor (VEGF) in malignant pericardial effusion and diagnostic value of pericardial VEGF levels to discriminate malignant from benign pericardial effusions are uncertain. HYPOTHESIS: We hypothesized that pericardial VEGF levels would be higher in malignant than benign pericardial effusion and that VEGF would be a useful marker for the diagnosis of malignant pericardial effusion. METHODS: Using an enzyme linked immunosorbent assay, we assessed pericardial and serum VEGF levels in patients with malignant pericardial effusion (n = 19), in patients with nonmalignant pericardial effusion (n = 30), and for control, in patients without pericardial disease (n = 26). RESULTS: Vascular endothelial growth factor pericardial levels in malignant pericardial effusion (13 593.8 +/- 22 410.24 pg/mL) were significantly higher compared with VEGF in nonmalignant effusion (610.63 +/- 1289.08 pg/mL; P = 0.001) and pericardial fluid (5.5 +/- 15.97 pg/mL; P < 0.001). In serum, VEGF was significantly higher in patients with nonmalignant pericardial effusion (188.3 +/- 240.35 pg/mL) compared with patients with malignant pericardial effusion (67.52 +/- 125.77 pg/mL; P = 0.024) and coronary artery disease patients (29.13 +/- 76.26 pg/mL; P < 0.001). Pericardial VEGF levels were significantly higher than matched serum levels only in patients with malignant pericardial effusion (P = 0.023). Pericardial VEGF levels >=2385 pg/mL had 75% sensitivity and 90% specificity for the recognition of malignant pericardial effusion in patients with breast or lung cancer. CONCLUSIONS: Vascular endothelial growth factor levels in pericardial effusion are markedly elevated in patients with malignant pericardial effusion, indicating abundant local release within the pericardial cavity. It is thus possible that VEGF participates in the pathogenesis of malignant pericardial effusion. Measurement of VEGF in pericardial effusion offers potential as a diagnostic tool to discriminate malignant from benign effusions in patients with breast or lung cancer. PMID- 22302719 TI - Effect of letrozole on uterine artery Doppler flow indices prior to first trimester termination of pregnancy: a randomized controlled trial. AB - OBJECTIVE: We previously demonstrated that a sequential regimen of letrozole and misoprostol resulted in a marked reduction in the serum estradiol concentration and in a higher efficacy of first-trimester termination of pregnancy than misoprostol alone. The aim of this study was to evaluate the effect of letrozole on uterine artery Doppler flow indices during early pregnancy. METHODS: This was a randomized controlled trial. Thirty women requesting termination of pregnancy up to 63 days' gestation were randomized into two groups: a letrozole group receiving 10 mg of letrozole, daily, for 3 days, and a control group receiving a placebo for 3 days. Serum estradiol, progesterone and human chorionic gonadotropin (hCG) concentrations were measured before drug administration and then daily for 6 days. Ultrasound scanning for fetal viability and measurement of the pulsatility (PI) and resistance (RI) indices of the uterine arteries was performed before drug administration, and then on day 3 and day 7 after starting letrozole or placebo. All pregnancies were terminated by surgical evacuation on day 7 or day 8. RESULTS: Uterine artery PI and RI decreased significantly in the letrozole group, but not in the control group. Serum estradiol concentrations were significantly lower in the letrozole group than in the control group from day 2 onwards. Serum progesterone and hCG concentrations were comparable for the two groups throughout the 7 days. There were significantly more women in the letrozole group with vaginal bleeding. CONCLUSION: We have demonstrated that the use of letrozole in the first trimester of pregnancy suppresses serum estradiol levels but results in an increase in blood flow to the uterus. Further studies should be carried out to elucidate the mechanism of letrozole pretreatment in medical abortion. PMID- 22302720 TI - Editorial. PMID- 22302721 TI - Brain mechanisms of social cognition. PMID- 22302722 TI - Brain mechanisms for 'having a theory of mind'. PMID- 22302723 TI - Psychopharmacology of maternal behaviour. PMID- 22302724 TI - Psychosocial factors and depression and anxiety disorders- some possible implications for biological research. PMID- 22302725 TI - 5 -HT, antidepressant drugs and the psychosocial origins of depression. PMID- 22302726 TI - Behavioural and neurochemical effects of early social deprivation in the rat. AB - The behavioural and neurochemical sequelae of rearing in early social isolation are reviewed. Rats isolated from their peers at ~ 20 days of age are hyperactive, exhibit ambivalent responses to novelty, altered response to stressors, and cognitive impairments when tested as adults. They also overrespond to stimuli predictive of reinforcement, as shown by their elevated levels of conditioned activity when the presentation of food reliably follows daily activity tests in photocell cages. The dose-effect curve for D-amphetamine is shifted to the left in this situation, confirming the enhanced locomotor and stereotyped behaviours seen following systemic treatment with a variety of other psychomotor stimulant drugs. In vivo measurement of amine activity in isolates using microdialysis shows elevations in dopamine concentration in both the nucleus accumbens (ventral striatum) and the caudate-putamen. There are also changes in central 5-HT metabolism. These results are considered in the light of recent studies in isolates using the latent inhibition or pre-pulse inhibition procedures, two putative models of the attentional dysfunction in schizophrenia. Finally, the implications of these findings are considered and future problems requiring resolution are raised. PMID- 22302727 TI - Social communication and its disorder in autism and Asperger syndrome. PMID- 22302728 TI - The psychopharmacology of autism and related disorders. PMID- 22302729 TI - Stimulant-induced disruption of non-human primate social behavior and the psychopharmacology of schizophrenia. PMID- 22302730 TI - Sexual selection as the mechanism of evolution of Machiavellian intelligence: a Darwinian theory of the origins of psychosis. PMID- 22302731 TI - Non-immune hydrops fetalis: a short review of etiology and pathophysiology. AB - Hydrops fetalis is an excessive accumulation of fetal fluid. Hydrops is traditionally classified into either immune or non-immune hydrops (NIHF), but in practice, nowadays in the Western world >90% of hydrops is of non-immune origin. The basis of the disorder is an imbalance in the regulation of fetal fluid movement between the vascular and interstitial space. We previously suggested a diagnostic flow-chart for NIHF. In this short review we describe the main mechanisms leading to NIHF. PMID- 22302732 TI - Cultural adaptation, validity, reliability and responsiveness of the Swedish version of the effective musculoskeletal consumer scale (EC-17). AB - BACKGROUND: Endorsed by the Outcome MEasures in Rheumatoid Arthritis in Clinical Trials (OMERACT) group, The Effective Consumer Scale (EC-17) was developed in English for patients with musculoskeletal diseases to assess the skills and perceptions important for participating in and managing health care. The objective of this study was culturally to adapt the questionnaire into Swedish and to study its psychometric properties. METHODS: After translation of the questionnaire into Swedish, two different groups of outpatients from two specialist rheumatology departments participated in the study. Face validity was assessed, together with internal consistency, test-retest and responsiveness of the questionnaire. Construct validity was assessed using the Arthritis Self Efficacy Scale (ASES), and responsiveness to a five day educational intervention was analysed using the standardized response mean (SRM). RESULTS: Analyses were based on 124 patients with inflammatory rheumatic diseases, of whom 50 attended the intervention. Data quality met the requirements, with missing values <5%, and floor and ceiling effects <15%. Item total correlations were all >0.4, ranging from 0.49 to 0.88. Cronbach's alpha was 0.93 and 0.95 for the two groups. The test-retest correlation (ICC2.1) was 0.94, and there was a significant improvement as a result of the intervention, with an SRM of 0.43. However, the questionnaire had a higher construct validity with the ASES subscale 'other symptoms' than hypothesized a priori (r(s) 0.75). CONCLUSION: The Swedish version of the EC-17 met the required recommendations for face validity, internal consistency, test-retest reliability and responsiveness. Its construct validity needs to be further established, and the questionnaire needs further testing in different groups of patients and in different interventions. PMID- 22302733 TI - Peritonitis in recent years: clinical findings and predictors of treatment response of 170 episodes at a single Brazilian center. AB - PURPOSE: Peritonitis continues to be a major cause of dropout in peritoneal dialysis (PD) patients. Changes in the prevalence of peritonitis etiologies and an increase in the frequency of methicillin-resistant coagulase-negative staphylococci (CoNS) and Gram-negative species resistant to commonly used antibiotics have been reported. As a consequence, the current clinical presentation and patient outcome may differ from classical descriptions. The objectives of this study were to describe the clinical and microbiological characteristics of PD-related peritonitis episodes that occurred over a period of 6 years at a single Brazilian dialysis center and to identify predictors of outcome. METHODS: A total of 170 peritonitis episodes that occurred in 92 PD patients between January 2004 and December 2009 were reviewed. Multivariate analysis was used to identify demographic, clinical, and microbiological factors predicting endpoints (resolution and peritonitis-related death). Patients' characteristics and peritonitis incidence, etiology and outcomes were compared with a series of 232 episodes that occurred in the first 6 years (1995-2000) of the PD program at the same center. RESULTS: The overall peritonitis rate was 0.65 episodes/patient-year. Gram-positive cocci were identified in 79 (46.5%) episodes, whereas Gram-negative bacilli were isolated from 48 (28.2%). CoNS were the main Gram-positive species identified in 48 episodes. Of these, 56.3% were resistant to methicillin. Among Gram-negative species, amikacin resistance was observed in 60% of non-fermentative Gram-negative bacilli (NFGNB) and in only 3.6% of Enterobacteriaceae. The overall resolution rate was 44.1%. Oxacillin resistance and NFGNB etiology were strong predictors of non-resolution, whereas older age was the only predictor of death. Antibiotic protocols did not influence outcome. Comparison with the results obtained for the 1990-1995 period showed a lower peritonitis rate, a strong decline in the proportion of Staphylococcus aureus episodes, a significant increase in the frequency of oxacillin-resistant CoNS and amikacin-resistant NFGNB, and a significantly lower resolution and higher death rate. CONCLUSIONS: The current clinical characteristics and outcome suggest a greater severity of peritonitis episodes and higher risk of death, possibly due to bacterial resistance. Older age is a risk factor for death. PMID- 22302734 TI - Can we identify the limits of the puborectalis/pubovisceralis muscle on tomographic translabial ultrasound? AB - OBJECTIVE: In order to determine the relative locations of puborectalis/pubovisceralis (PR/PV) and iliococcygeus (IC) muscles, we undertook an analysis of four-dimensional (4D) ultrasound datasets obtained after suburethral sling placement. METHODS: This was a retrospective analysis of ultrasound volume data obtained in 110 women after undergoing the Monarc suburethral sling procedure. Tomographic ultrasound imaging (TUI) was performed with eight slices in the axial plane, from 5 mm below to 12.5 mm above the plane of minimal hiatal dimensions. Hyperechogenic tape material was rated as absent, present or as producing an anechoic acoustic shadow overlying the muscle in each slice. RESULTS: Slices 7 and 8 virtually always showed evidence of the implant or its acoustic shadow on the pelvic sidewall (98% for slice 8 and 96% for slice 7), suggesting that these slices are located at the level of the obturator foramen. This implies that these slices do not generally contain PR/PV muscle, but rather IC muscle. CONCLUSION: On standardized tomographic imaging of the levator hiatus and muscle, slices located >= 1 cm over the plane of minimal dimensions are very likely to contain IC muscle rather than PR/PV muscle. PMID- 22302735 TI - Core-shell potential-derived point charges. AB - The present work details the development of a core-shell model for the purposes of obtaining potential-derived point charges from the ab initio molecular electrostatic potential. In contrast to atomic point charge models, the core shell model decomposes all atoms into a core with static charge located at a fixed atomic position and a shell with variable charge and position. The optimization of shell charges and positions is discussed. The core-shell model was found to significantly improve description of the ab initio electrostatic potential when compared to potential-derived net atomic point charge models as well as distributed multipoles with contributions up to atomic quadrupole moments. The core-shell model was found to produce similar results as the Weller Williams lone-pair model and differences in the implementation of the models are discussed. PMID- 22302736 TI - Chromosome 22q11.2 duplication is rare in a population-based cohort of Danish children with cardiovascular malformations. AB - The prevalence of the 22q11.2 duplication is unknown in children with cardiovascular malformations (CVMs). As most individuals with the duplication are detected in the search for other conditions, especially the 22q11.2 deletion, CVMs associated with the duplication are subject to referral bias. We circumvented this bias by investigating the prevalence of the 22q11.2 duplication in a population-based cohort of children with CVMs. The study population was defined as children born in 2000-2008, who were registered in the Danish National Patient Registry with a diagnosis of CVM from one of the two national university departments of pediatric cardiology. Sensitive multiplex ligation-dependent probe amplification was performed on dried blood spot samples from each individual's neonatal screening test. The study population consisted of 2,952 children with CVMs, 2,424 of whom were eligible for genetic testing; 13 individuals (0.5% [0.3 0.9%]) carried the duplication. Nine individuals (69%) had not previously been tested for a copy number variation on chromosome 22q11.2 in the clinical setting for children with CVMs. We conclude that 22q11.2 duplication is rare in children with CVMs, and is primarily found in malformations that are also associated with the 22q11.2 deletion. PMID- 22302737 TI - How I treat with anticoagulants in 2012: new and old anticoagulants, and when and how to switch. AB - Two novel oral anticoagulants, dabigatran and rivaroxaban, have recently been approved. They differ in many ways from warfarin, including rapid onset of action, shorter half-life, fewer drug-drug interactions, lack of need for monitoring, and no need for titration or dose adjustments. These novel agents represent a landmark shift in anticoagulant care; however, many aspects of their use will be unfamiliar to practicing clinicians, despite the imminent widespread use of these agents in the community. The management of these anticoagulants when transitioning from or back to warfarin, around surgery or in case of major hemorrhage, requires knowledge of their pharmacokinetics and mechanism of action. Unfortunately, there is a limited evidence base to inform decisions around management of these agents. We present our practice in these settings supported, where available, with literature evidence. PMID- 22302738 TI - Human CD300a binds to phosphatidylethanolamine and phosphatidylserine, and modulates the phagocytosis of dead cells. AB - CD300a is an immunoreceptor tyrosine-based inhibitory motif (ITIM) containing molecule that belongs to the CD300 family of paired activating/inhibitory receptors. It has been shown that its ligation inhibits activation signals on cells of both myeloid and lymphoid lineages. The ligands for CD300a have not been identified. Here, we show that a CD300a-Ig fusion protein specifically binds to apoptotic cells that are evolutionary apart, such as human and insect cells, suggesting that the ligand has to be conserved. Using surface plasmon resonance, ultracentrifugation, ELISA, and reporter cell assays, we identified phosphatidylethanolamine (PE) and phosphatidylserine (PS), 2 phospholipids that translocate to the outer leaflet of the plasma membrane of dead cells, as the ligands for CD300a. Mutational and structural modeling studies identified residues that are involved in the binding of CD300a to PE and PS and that form a cavity where the hydrophilic heads of PE and PS, can penetrate. CD300a down regulates the uptake of apoptotic cells by macrophages and its ectopic expression in CD300a-negative cell lines also decreased the engulfment of dead cells. Collectively, our results indicate that PE and PS are ligands for CD300a, and that this interaction plays an important role in regulating the removal of dead cells. PMID- 22302740 TI - Improvement of light emission of Mn-doped Zn2 SiO4 phosphors with sodium. AB - Mn-doped willemite (Zn2 SiO4 :Mn) green phosphor were synthesized by sol-gel technology. The effect of the addition of sodium, as in the composition Zn((1.92 X)) Na(X) Mn(0.08) SiO4, on the emission behavior was studied. FT-IR and EPR results revealed that sodium ion is incorporated into the lattice and results in the formation of isolated Mn2+ and Mn-Mn pairs. The maximum emission intensity of the sample under ultraviolet (UV) excitation occurred at the sodium concentration of x = ~0.03. The green emission at about 525 nm is assigned to Mn2+ -Mn2+ pair centres on nearest neighbour Zn sites. The highest intensity of the green emission for x = ~0.03 is well close to the highest concentration of the Mn2+ Mn2+ pair. PMID- 22302739 TI - B cell-intrinsic deficiency of the Wiskott-Aldrich syndrome protein (WASp) causes severe abnormalities of the peripheral B-cell compartment in mice. AB - Wiskott Aldrich syndrome (WAS) is caused by mutations in the WAS gene that encodes for a protein (WASp) involved in cytoskeleton organization in hematopoietic cells. Several distinctive abnormalities of T, B, and natural killer lymphocytes; dendritic cells; and phagocytes have been found in WASp deficient patients and mice; however, the in vivo consequence of WASp deficiency within individual blood cell lineages has not been definitively evaluated. By conditional gene deletion we have generated mice with selective deficiency of WASp in the B-cell lineage (B/WcKO mice). We show that this is sufficient to cause a severe reduction of marginal zone B cells and inability to respond to type II T-independent Ags, thereby recapitulating phenotypic features of complete WASp deficiency. In addition, B/WcKO mice showed prominent signs of B-cell dysregulation, as indicated by an increase in serum IgM levels, expansion of germinal center B cells and plasma cells, and elevated autoantibody production. These findings are accompanied by hyperproliferation of WASp-deficient follicular and germinal center B cells in heterozygous B/WcKO mice in vivo and excessive differentiation of WASp-deficient B cells into class-switched plasmablasts in vitro, suggesting that WASp-dependent B cell-intrinsic mechanisms critically contribute to WAS-associated autoimmunity. PMID- 22302741 TI - Cranial osteopathic manipulative medicine's growing evidence base. PMID- 22302742 TI - Role of the musculoskeletal system and the prevention of falls. AB - Approximately 30% of older adults fall at least once per year, with falls being the leading cause of fatal and nonfatal injuries for individuals in this age group. Because of projected increases in the older adult population, the annual cost of fatal and nonfatal fall-related injuries is estimated to reach $32.4 billion in 2020. Falls in older adults are likely due to an interaction of multiple risk factors, including vitamin D deficiency, diminished strength and coordination, depression, multiple medications, and home hazards. Ultimately, the evidence supports a multifaceted approach to screening for fall-related risk factors and targeting treatment to address specific risks for each patient. While keeping in mind that the patient is the product of the dynamic interaction of body, mind, and spirit, the osteopathic physician is well suited to provide comprehensive, patient-centered care. PMID- 22302743 TI - Use of therapies other than disease-modifying agents, including complementary and alternative medicine, by patients with multiple sclerosis: a survey study. AB - CONTEXT: Many patients with multiple sclerosis use complementary and alternative medicine (CAM) to supplement their traditional treatment. OBJECTIVE: To identify both the prevalence and frequency of use of therapies other than disease modifying agents (DMAs), including CAM, among patients with multiple sclerosis. DESIGN: The authors administered a 13-question survey regarding patients' current use of non-DMA therapies-including dietary supplements, exercise, and "true" CAM (eg, acupuncture, chiropractic, massage)-and mainstream treatments, including physical therapy and osteopathic manipulative treatment. Patients rated their level of disability on a scale of 1 to 10 (with 10 being most severe). SETTING: A hospital outpatient clinic in Philadelphia, Pennsylvania. PATIENTS: Inclusion criteria were physician-confirmed multiple sclerosis (either relapsing-remitting or progressive), regardless of sex, duration of disease, age at onset, disability level, or type of disease. Patients were excluded if they were younger than 18 years. MAIN OUTCOME MEASURE: Patient-reported use of non-DMA therapies and perception of disability. RESULTS: A total of 111 patients with multiple sclerosis completed the survey properly. All respondents used non-DMA therapies. Twenty-three patients (20.7%) used these therapies without concomitantly taking a DMA. A plurality (34.8%) of those patients reported a disability score of 7 or 8. Sixty-two of the 88 participants (70.5 %) who used DMAs reported disability scores of 5 or less. Sixty-five patients (58.6.%) reported exercising on a weekly basis. Among those patients, 47 (72.3%) reported a disability score of 5 or less. Sixty-four patients (57.7%) used such CAM therapies as acupuncture and massage, or such other non-DMA treatments as osteopathic manipulative treatment and psychotherapy. Among those patients, 37 (64.9%) reported a disability score of 5 or less. CONCLUSION: Many patients with multiple sclerosis are seeking more than traditional medical treatment. Physicians and other health care professionals must be aware of the extensive use of alternative modalities among these patients, and these professionals must provide guidance and monitoring in use of these therapies to improve outcomes. PMID- 22302744 TI - Megacolon presenting as anemia. PMID- 22302747 TI - R179H mutation in ACTA2 expanding the phenotype to include prune-belly sequence and skin manifestations. AB - Mutations in ACTA2 (smooth muscle cell-specific isoform of alpha-actin) lead to a predisposition to thoracic aortic aneurysms and other vascular diseases. More recently, the ACTA2 R179H mutation has been described in individuals with global smooth muscle dysfunction. We report a patient heterozygous for the mutation in ACTA2 R179H who presented with megacystis at 13 weeks gestational age and, at birth, with prune-belly sequence. He also had deep skin dimples and creases on his palms and soles, a finding not previously described but possibly related to ACTA2. To our knowledge, this is the first report of the R179H mutation in ACTA2 in a child with prune-belly sequence. We think the R179H mutation in ACTA2 should be included in the differential diagnosis of individuals presenting with the sequence without an identified mechanical obstruction. Furthermore, as ACTA2 R179H has been reported in patients with severe vasculomyopathy and premature death, we recommend that molecular testing for this mutation be considered in fetuses presenting with fetal megacystis with a normal karyotype, particularly if the bladder diameter is 15 mm or more, to allow expectant parents to make an informed decision. PMID- 22302748 TI - Quantification of fetal head direction using transperineal ultrasound: an easier approach. PMID- 22302749 TI - Minimally ablative resurfacing with the confluent 2,790 nm erbium:YSGG laser: a pilot study on safety and efficacy. AB - BACKGROUND: The 2,790 nm Er:YSGG wavelength has a lower water absorption coefficient than the 2,940 nm Er:YAG, but a higher coefficient than the 10,600 nm CO(2) laser. This allows ablative resurfacing with mild thermal coagulation, which may increase clinical efficacy while reducing patient downtime. OBJECTIVES: To evaluate the efficacy and safety of the confluent 2,790 nm Erbium:YSGG (PearlTM, Cutera) laser for facial rejuvenation. STUDY DESIGN/MATERIALS AND METHODS: Eleven subjects (mean age 50, skin types I-III) with mild to moderate photodamage and wrinkles had two facial treatments with the 2,790 nm Er:YSGG laser using a fluence of 3.5 J/cm(2), pulse duration of 0.4 msecond, and 20% overlap. Treatments were performed 6 weeks apart. Pre-auricular biopsies from five subjects were evaluated at baseline and 6 weeks after the final treatment. Data from blinded photo assessments and subjects' self-assessment of improvement were analyzed 6 weeks after the final treatment. Additionally, long-term safety and efficacy were evaluated 2 years after the final treatment. RESULTS: Histologically, 80% of subjects had new collagen formation in the dermal grenz zone, and 60% had increased epidermal thickness. Almost all subjects (91%) showed improvement in tone/texture, 82% of subjects showed improvement in dyschromia and fine lines, and 54% showed improvement in wrinkles 6 weeks after the final treatment. Subjects' self assessment indicated "significant" to "dramatic" improvement in dyschromia (91% of subjects) and tone/texture (82%) 6 weeks after the final treatment. All subjects saw "mild" to "significant" improvement in fine lines and wrinkles. At the 2-year follow-up visit, 57% of the overall improvement achieved at 6 weeks was maintained. No adverse events were reported throughout the study. CONCLUSION: Ablative resurfacing with the 2,790 nm Er:YSGG laser demonstrated visible improvement in photodamage with good tolerability and minimal downtime. Subjects were highly satisfied, especially with respect to dyschromia, skin tone, and texture. PMID- 22302750 TI - When silence is broken: polycomb group proteins in heart development. PMID- 22302751 TI - Nur77turing macrophages in atherosclerosis. PMID- 22302752 TI - Endonuclease G: the link between mitochondria and cardiac hypertrophy? PMID- 22302753 TI - James Willerson: leading the Texans' fight against heart disease. Interview by Ruth Williams. PMID- 22302754 TI - Introduction to the series on microRNAs in the cardiovascular system. AB - Until recently, microRNAs (miRNAs) were considered to be relatively small players in biological systems by having a balancing function through moderate effects on gene expression levels. However, it has become appreciated that miRNAs are actually much more relevant during both development and disease, which is underscored by the attention they have been receiving. The goal of this thematic review series is to highlight current knowledge of miRNA function during cardiovascular development, their dysregulation under disease conditions and the disease modifying functions they have been shown to exert in the cardiovascular system. These reviews, in addition to discussing the recent advancements in using miRNAs as circulating biomarkers or therapeutic modalities, will hopefully be able to provide a strong basis for future research to further expand our insights into miRNA function in cardiovascular biology. PMID- 22302755 TI - Circulating microRNAs: novel biomarkers and extracellular communicators in cardiovascular disease? AB - In the past few years, the crucial role of different micro-RNAs (miRNAs) in the cardiovascular system has been widely recognized. Recently, it was discovered that extracellular miRNAs circulate in the bloodstream and that such circulating miRNAs are remarkably stable. This has raised the possibility that miRNAs may be probed in the circulation and can serve as novel diagnostic markers. Although the precise cellular release mechanisms of miRNAs remain largely unknown, the first studies revealed that these circulating miRNAs may be delivered to recipient cells, where they can regulate translation of target genes. In this review, we will discuss the nature of the stability of miRNAs that circulate in the bloodstream and discuss the available evidence regarding the possible function of these circulating miRNAs in distant cell-to-cell communication. Furthermore, we summarize and discuss the usefulness of circulating miRNAs as biomarkers for a wide range of cardiovascular diseases such as myocardial infarction, heart failure, atherosclerosis, hypertension, and type 2 diabetes mellitus. PMID- 22302756 TI - Developing microRNA therapeutics. AB - Rarely a new research area has gotten such an overwhelming amount of attention as have microRNAs. Although several basic questions regarding their biological principles still remain to be answered, many specific characteristics of microRNAs in combination with compelling therapeutic efficacy data and a clear involvement in human disease have triggered the biotechnology community to start exploring the possibilities of viewing microRNAs as therapeutic entities. This review serves to provide some general insight into some of the current microRNAs targets, how one goes from the initial bench discovery to actually developing a therapeutically useful modality, and will briefly summarize the current patent landscape and the companies that have started to explore microRNAs as the next drug target. PMID- 22302757 TI - MicroRNAs in vascular and metabolic disease. AB - Recent findings demonstrated the importance of microRNAs (miRNAs) in the vasculature and the orchestration of lipid metabolism and glucose homeostasis. MiRNA networks represent an additional layer of regulation for gene expression that absorbs perturbations and ensures the robustness of biological systems. This function is very elegantly demonstrated in cholesterol metabolism where miRNAs reducing cellular cholesterol export are embedded in the very same genes that increase cholesterol synthesis. Often their alteration does not affect normal development but changes under stress conditions and in disease. A detailed understanding of the molecular and cellular mechanisms of miRNA-mediated effects on metabolism and vascular pathophysiology could pave the way for the development of novel diagnostic markers and therapeutic approaches. In the first part of this review, we summarize the role of miRNAs in vascular and metabolic diseases and explore potential confounding effects by platelet miRNAs in preclinical models of cardiovascular disease. In the second part, we discuss experimental strategies for miRNA target identification and the challenges in attributing miRNA effects to specific cell types and single targets. PMID- 22302758 TI - Circadian variations of infarct size in STEM1. PMID- 22302759 TI - Population-based survival for childhood cancer patients diagnosed during 2002 2005 in Shanghai, China. AB - BACKGROUND: There have been no population-based studies on cancer survival among children aged 0-14 years in China. In this study, we aimed to characterize the cancer survival among children in Shanghai. PROCEDURE: Childhood cancer cases registered by the Shanghai Cancer Registry between 2002 and 2005 and enrolled in the Shanghai Childhood Survival Study were included in this study. We used Kaplan Meier product-limit method for survival analysis and Cox proportional hazards models for investigating the effects of various prognostic factors. RESULTS: The median follow-up time was 5.4 years (range 0-8.9 years). The 5-year observed survival for all childhood cancers combined was 55.7% (95% CI: 51.7-59.6%). For leukemia, lymphoma, and central nervous system tumors, the three most common types of childhood cancer, 5-year survival rates were 52.2%, 58.8%, and 41.2%, respectively. Higher 5-year survival rates were observed for epithelial cancer (88.9%), malignant renal tumors (86.7%), germ cell and other gonadal tumors (78.4%), and retinoblastoma (75.0%). Cancers with poor prognosis included sympathetic nervous system tumors (57.9%), soft tissue sarcoma (54.1%), bone tumors (52.6%), and liver cancer (33.3%). There were no significant differences between survival rates by gender and age groups. Compared with those reported in the USA and Europe, the survival rates for all cancers combined and the three most common types in Shanghai were lower. CONCLUSIONS: The survival rate for children aged 0-14 diagnosed with cancer in Shanghai during 2002-2005 was at the medium level. There was a substantial survival difference from childhood cancers between Shanghai and specific developed countries. PMID- 22302760 TI - Informing on prenatal screening for Down syndrome prior to conception. An empirical and ethical perspective. AB - In most Western countries, information on prenatal screening for Down syndrome is provided in the first-trimester of pregnancy. The purpose of this study was to examine whether this information should additionally be provided before pregnancy to improve the informed decision-making process. In an empirical study, we obtained data from pregnant women with respect to their preferences regarding information on prenatal screening preconceptionally. Questionnaire data (n = 510) showed that 55.7% of responding women considered participating in prenatal screening for Down syndrome before pregnancy. 28.0% of women possessed information on prenatal screening preconceptionally. 84.6% preferred not to receive information preconceptionally in retrospect. In an ethical analysis, we elaborated on these preferences by weighing pros and cons. We considered two arguments against the provision of information on prenatal screening preconceptionally: women's preference to receive information in a step-by-step manner, and the risk of providing a directive message. We identified three reasons supporting its provision preconceptionally: the likelihood of making an informed decision could, firstly, be increased by "unchaining" the initial information from possible subsequent decisions, and, secondly, by providing women sufficient time to deliberate. Thirdly, the probability of equal access to prenatal screening may increase. To conclude with, we propose to incorporate an information offer on prenatal screening for Down syndrome in preconception care consultations. By offering information, instead of providing information, prospective parents are enabled to either accept or decline the information, which respects both their right to know and their right not-to-know. PMID- 22302761 TI - Can fractional lasers enhance transdermal absorption of topical lidocaine in an in vivo animal model? AB - BACKGROUND AND OBJECTIVE: It has been shown in vitro that pretreatment of skin with fractional lasers enhances transdermal delivery of drugs. The aim of this study is to demonstrate in vivo firstly that laser enhances transdermal drug absorption and secondly that this can be manipulated by altering laser settings. STUDY DESIGN/MATERIALS AND METHODS: Four pigs were used in the IACUC approved animal study. On day 0, 5 g of 4% topical lidocaine was applied under occlusion for 60 minutes to a 400 cm(2) area on the abdomen. Blood was drawn at 0, 60, 90, 120, 180, and 240 minutes. On day 7, the Er:YAG laser was used at 500, 250, 50, and 25 um ablative depth, respectively, over a 400 cm(2) area on the abdomen. Five grams of 4% topical lidocaine was applied immediately with occlusion for 60 minutes, and then removed. Blood was drawn at 0, 60, 90, 120, 180, and 240 minutes. The serum was extracted and analyzed for lidocaine and its metabolite monoethylglycinexylidide (MEGX). RESULTS: Serum levels of lidocaine and MEGX were undetectable in untreated skin. Following laser treatment both lidocaine and MEGX were detectable. Peak levels of lidocaine were significantly higher (P = 0.0002) at 250 um (0.62 mg/L), compared to 500 um (0.45 mg/L), 50 um (0.48 mg/L), and 25 um (0.3 mg/L). Peak levels of MEGX were significantly higher (P <= 0.0001) at 250 um (0.048 mg/L), compared to 500 um (0.018 mg/L), 50 um (0.036 mg/L), and 25 um (0.0144 mg/L). CONCLUSIONS: This study demonstrates that laser pretreatment significantly increases absorption of topical lidocaine so that it is detectable in the blood and that manipulating laser settings can affect drug absorption. Future work will look at translating this effect into clinical benefit. PMID- 22302762 TI - Dynamic telecytopathology for on-site preliminary diagnosis of endoscopic ultrasound-guided fine needle aspiration of pancreatic masses. AB - We evaluated dynamic telecytopathology for on-site-evaluation of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) samples of the pancreas. Realtime images of stained cytology smears were assessed by a cytopathologist while communicating with the on-site operator by telephone. A total of 55 consecutive cases was assessed; preliminary diagnoses of benign, atypical/suspicious and positive for malignancy were 69%, 7% and 24%. We also reviewed 55 consecutive cases of EUS-guided FNA of pancreas which had had conventional microscopic on-site evaluation prior to the introduction of telecytopathology. Preliminary diagnoses of benign, atypical/suspicious and positive for malignancy were 60%, 9% and 31%. The overall concordance between the preliminary and final diagnosis was 84% for telecytopathology and 87% for conventional microscopy. Neuroendocrine neoplasms and well-differentiated adenocarcinoma were diagnostically challenging for both telecytopathology and conventional microscopy. Telecytopathology was similar in accuracy of preliminary diagnosis to conventional microscopy during EUS-FNA of pancreas. PMID- 22302763 TI - An analysis of a videoconference-based teleconsultation system in Bangladesh. PMID- 22302764 TI - The use of telehealth to assist remote hospital resuscitation and aeromedical retrieval tasking: a 12-month case review. AB - We evaluated the use of telehealth for patients who had suffered a cardiac or respiratory arrest, and were medically coordinated from the Queensland coordination hub at Townsville. We conducted a review of all cardiac or respiratory arrest cases where teleheath had been used prior to aeromedical retrieval. The doctors involved in the cases completed an evaluation form about the use of telehealth during the resuscitation. During the 12-month study period 6460 patients were medically coordinated from Townsville. Telehealth was used 51 times, i.e. for 0.8% of all transfers. Of the 51 uses of telehealth, nine were for patients having a cardiac/respiratory arrest, i.e. 18% of telehealth use at Townsville was for patients undergoing resuscitation following cardiac or respiratory arrest. All eight medical coordinators and three of eight referring doctors responded to the survey. Most medical coordinators stated that telehealth assisted communication and aided assessment. Most medical coordinators and some referring doctors felt that it improved the quality of patient care. The free text comments on telehealth use for remote area resuscitation were generally very supportive. While the telehealth equipment was easy to use, minor audio problems reinforce the need for systems to be wholly reliable. A set of guidelines to aid future telehealth assisted resuscitation was produced. The present study suggests that telehealth use is beneficial during active resuscitation efforts. PMID- 22302765 TI - Personalised electronic messages to improve sun protection in young adults. AB - We studied the acceptability and feasibility of delivering sun protection messages via electronic media such as short message services (SMS) to people aged 18-40 years. An online survey was conducted using a pre-established panel of volunteers. We compared the characteristics of those who indicated that they would like to be alerted to the UV index, with those who would not, using bivariate logistic regression. Characteristics found to be associated with a desire to receive such advice were entered into a multivariate logistic regression analysis. The median age of the 141 participants was 34 years. Overall, 80% of participants agreed that they would like to receive some form of sun protection advice. Of these, 20% preferred to receive it via SMS and 42% via email. Willingness to receive electronic messages about the UV index was associated with being unsure about whether a suntanned person would look healthy and greater use of sun protection in the past. Careful attention to message framing and timing of message delivery, and focus on the short-term effects of sun exposure such as sunburn and skin ageing should increase the acceptability of such messages to young people. Sun protection messages delivered to young adults via electronic media appear to be feasible and acceptable. PMID- 22302766 TI - Prefrontal space ratio: comparison between trisomy 21 and euploid fetuses in the second trimester. AB - OBJECTIVE: To evaluate a novel ultrasound measurement, the prefrontal space ratio (PFSR), in second-trimester trisomy 21 and euploid fetuses. METHODS: Stored three dimensional volumes of fetal profiles from 26 trisomy 21 fetuses and 90 euploid fetuses at 15-25 weeks' gestation were examined. A line was drawn between the leading edge of the mandible and the maxilla (MM line) and extended in front of the forehead. The ratio of the distance between the leading edge of the skull and that of the skin (d(1)) to the distance between the skin and the point where the MM line was intercepted (d(2)) was calculated (d(2)/d(1)). The distributions of PFSR in trisomy 21 and euploid fetuses were compared, and the relationship with gestational age in each group was evaluated by Spearman's rank correlation coefficient (r(s) ). RESULTS: The PFSR in trisomy 21 fetuses (mean, 0.36; range, 0-0.81) was significantly lower than in euploid fetuses (mean, 1.48; range, 0.85 2.95; P < 0.001 (Mann-Whitney U-test)). There was no significant association between PFSR and gestational age in either trisomy 21 (r(s) = 0.25; 95% CI, - 0.15 to 0.58) or euploid (r(s) = 0.06; 95% CI, - 0.15 to 0.27) fetuses. CONCLUSION: The PFSR appears to be a highly sensitive and specific marker of trisomy 21 in the second trimester of pregnancy. PMID- 22302767 TI - Chromenopyrazoles: non-psychoactive and selective CB1 cannabinoid agonists with peripheral antinociceptive properties. AB - The unwanted psychoactive effects of cannabinoid receptor agonists have limited their development as medicines. These CB1-mediated side effects are due to the fact that CB1 receptors are largely expressed in the central nervous system (CNS). As it is known that CB1 receptors are also located peripherally, there is growing interest in targeting cannabinoid receptors located outside the brain. A library of chromenopyrazoles designed analogously to the classical cannabinoid cannabinol were synthesized, characterized, and tested for cannabinoid activity. Radioligand binding assays were used to determine their affinities at CB1 and CB2 receptors. Structural features required for CB1/CB2 affinity and selectivity were explored by molecular modeling. Some compounds in the chromenopyrazole series were observed to be selective CB1 ligands. These modeling studies suggest that full CB1 selectivity over CB2 can be explained by the presence of a pyrazole ring in the structure. The functional activities of selected chromenopyrazoles were evaluated in isolated tissues. In vivo behavioral tests were then carried out on the most effective CB1 cannabinoid agonist, 13 a. Chromenopyrazole 13 a did not induce modifications in any of the tested parameters on the mouse cannabinoid tetrad, thus discounting CNS-mediated effects. This lack of agonistic activity in the CNS suggests that this compound does not readily cross the blood-brain barrier. Moreover, 13 a can induce antinociception in a rat peripheral model of orofacial pain. Taking into account the negative results obtained with the hot plate test, the antinociception induced by 13 a in the orofacial test could be mediated through peripheral mechanisms. PMID- 22302768 TI - Weekend compared with weekday presentations of peritoneal dialysis-associated peritonitis. AB - OBJECTIVE: Management of peritoneal dialysis (PD)-associated peritonitis requires timely intervention by experienced staff, which may not be uniformly available throughout the week. The aim of the present study was to examine the effects of weekend compared with weekday presentation on peritonitis outcomes. METHODS: The study, which used data from the Australia and New Zealand Dialysis and Transplant Registry, included all Australian patients receiving PD between 1 October 2003 and 31 December 2008. The independent predictors of weekend presentation and subsequent peritonitis outcomes were assessed by multivariate logistic regression. RESULTS: Peritonitis presentation rates were significantly lower on Saturdays [0.46 episodes per year; 95% confidence interval (CI): 0.42 to 0.49 episodes per year] and on Sundays (0.43 episodes per year; 95% CI: 0.40 to 0.47 episodes per year) than all other weekdays; they peaked on Mondays (0.76 episodes per year; 95% CI: 0.72 to 0.81 episodes per year). Weekend presentation with a first episode of peritonitis was independently associated with lower body mass index and residence less than 100 km away from the nearest PD unit. Patients presenting with peritonitis on the weekend were significantly more likely to be hospitalized [adjusted odds ratio (OR): 2.32; 95% CI: 1.85 to 2.90], although microbial profiles and empiric antimicrobial treatments were comparable between the weekend and weekday groups. Antimicrobial cure rates were also comparable (79% vs 79%, p = 0.9), with the exception of cure rates for culture-negative peritonitis, which were lower on the weekend (80% vs 88%, p = 0.047). Antifungal prophylaxis was less likely to be co-prescribed for first peritonitis episodes presenting on weekdays (OR: 0.68; 95% CI: 0.05 to 0.89). CONCLUSIONS: Patients on PD are less likely to present with peritonitis on the weekend. Nevertheless, the microbiology, treatment, and outcomes of weekend and weekday PD peritonitis presentations are remarkably similar. Exceptions include the associations of weekend presentation with a higher hospitalization rate and a lower cure rate in culture-negative infection. PMID- 22302769 TI - Ultrafiltration and dialysis adequacy with various daily schedules of dialysis fluids. AB - Dialysis regimens for continuous ambulatory peritoneal dialysis (CAPD) patients vary with the need for fluid removal, but also because of concerns about the local and systemic consequences of high glucose exposure. The implications of various regimens for dialysis adequacy--that is, fluid and small-solute removal- are not always clear. We therefore analyzed ultrafiltration (UF) and adequacy indices for 4 different combinations of dialysis fluid. Collections of 24-hour dialysate and urine were carried out in 99 patients on CAPD. On 4 separate occasions, each patient performed 4 exchanges in 24 hours, including 3 daily exchanges with 1.36% glucose and 1 night exchange with either 1.36% glucose (G1 schedule), 2.27% glucose (G2 schedule), 3.86% glucose (G3 schedule), or icodextrin (Ico schedule). Weekly, total, and dialysis Kt/V and KT were calculated for both urea and creatinine. The mean values of urea Kt/V and KT were significantly lower for the G1 schedule than for the G3 and Ico schedules. The adequacy indices for overnight application of 3.86% glucose and icodextrin were similar. Using dialysis fluids with 1.36% and 2.27% glucose overnight reduces glucose exposure, but those schedules may provide inadequate UF and small-solute removal in some patients (UF < 1 L daily, Kt/V < 1.7). PMID- 22302770 TI - The effect on peritoneal dialysis pathogens of changing topical antibiotic prophylaxis. AB - BACKGROUND: Prophylactic gentamicin 0.1% cream has demonstrated efficacy in preventing both exit-site infection (ESI) and peritonitis attributable to gram positive and gram-negative organisms; however, the effect of this practice on the gentamicin susceptibility patterns of bacterial pathogens isolated from such infections is unknown. We therefore examined the effect of a change in our prophylactic topical antibiotic exit-site protocol (from mupirocin 2% cream to gentamicin 0.1% cream) on infection rates and susceptibility patterns. METHODS: This retrospective observational cohort study examined two periods of time: before and after the change in exit-site protocol. Each period was 30 months in duration, with a 2-month implementation period between, during which patient data were excluded. Demographic, clinical, and microbiology data were collected for each patient and episode of infection. RESULTS: Overall, 377 patients were evaluated. In the mupirocin period (MUP), 145 infections occurred in 79 patients, and in the gentamicin period, 145 infections occurred in 93 patients. No significant effect was found either in overall episodes of infection (0.53 per year) or in episodes of peritonitis (0.429 vs 0.375 per year), but episodes of ESI increased significantly (0.098 vs 0.153 per year; p = 0.024; odds ratio: 1.55; 95% confidence interval: 1.05 to 2.28). Episodes of Staphylococcus aureus peritonitis increased by 38% (0.018 vs 0.025 per year), and episodes of S. aureus ESI increased significantly by 150% (0.022 vs 0.055 per year; p = 0.03; hazard ratio: 3.00; 95% confidence interval: 1.09 to 8.26). Episodes of pseudomonal peritonitis declined by 68% (0.022 vs 0.007 per year), and episodes of pseudomonal ESI increased by 150% (0.007 vs 0.018 per year). The gentamicin susceptibility for gram-positive isolates demonstrated no significant change; however, the gentamicin susceptibility for Enterobacteriaceae decreased by 12% and for Pseudomonas, by 14%. CONCLUSIONS: The significant increase in episodes of ESI and the decrease in susceptibility for both Enterobacteriaceae and Pseudomonas isolates represent a concerning trend. Centers should examine trends in infection rates and in bacterial susceptibilities to determine the most appropriate agent for ESI prophylaxis. PMID- 22302771 TI - In vitro microbiology studies on a new peritoneal dialysis connector. AB - OBJECTIVE: We evaluated the ability of a recently developed peritoneal dialysis (PD) connector to prevent the risk of bacterial transfer to the fluid path after simulated touch and airborne contamination. METHODS: Staphylococcus epidermidis ATCC1228 and Pseudomonas aeruginosa ATCC27853 strains were used. For touch contamination, 2 MUL of a standardized inoculum [1*10(8) colony-forming units (CFU) per milliliter] were deposited on top of the pin closing the fluid path of the patient connector. For airborne contamination, the patient connector was exposed for 15 seconds to a nebulized standardized inoculum. To simulate the patient peritoneum and effluent, the patient connector was pre-attached to a 2-L bag of sterile PD solution. After contamination, the patient connector was attached to the transfer set, the pin was captured, flow control was turned to simulate "patient drain" into the empty bag, and then "patient fill" using the bag pre-attached to the connector. Finally, a new pin was recaptured. The PD solution collected in the bag pre-attached to the connector was run through a 0.20-MUm filter for colony counts. RESULTS: No infected connector transferred bacteria to the fluid path, regardless of the challenge procedure or the strain used. CONCLUSIONS: Our results show that the new PD connector may fully obviate the risk of bacterial infection, even in the presence of heavy contamination. Further studies are in progress to test our PD connector in a clinical setting. PMID- 22302772 TI - Diagnostic sensitivity of serum and lumbar CSF bHCG in newly diagnosed CNS germinoma. AB - BACKGROUND: Marked elevations of AFP and bHCG in serum or CSF may serve as surrogate diagnostic markers in lieu of histology for primary CNS mixed, malignant germ cell tumors. There is less information on the diagnostic sensitivity of bHCG assays in germinoma. PROCEDURE: We report baseline serum and lumbar CSF bHCG values in 58 newly diagnosed, histologically confirmed germinoma patients gathered from two prospective clinical trials which required that patients have a normal AFP and bHCG <=50 mIU/ml in serum and lumbar CSF. RESULTS: The location of the primary tumors was: suprasellar(23); pineal(20); suprasellar/pineal(9); and other sites(6). The mean age of the study population was 13.5 (4.3-25.9) years. A total of 23(40%) patients had elevations of bHCG in either serum or CSF, 20(34.5%) of whom had only bHCG elevations in CSF. The patients' bHCG profiles were divided into four categories: I (normal serum and lumbar CSF bHCG), 35(60%); II (normal serum and elevated CSF bHCG), 20(34.5%); III (elevated serum and CSF bHCG), 2(3.5%); and IV (elevated serum and normal CSF bHCG), 1(2%). The median CSF bHCG level was 7.7(2.5-16) in the 22 patients with abnormal CSF values and the lumbar value was higher than the serum value in 20 of 23(87%) patients with bHCG elevations. CONCLUSIONS: Lumbar CSF was a more informative screen for bHCG than serum but the majority of patients (60%) had normal bHCG values at diagnosis. Until a more sensitive tumor marker for germinoma is devised, histologic confirmation remains the standard of care. Pediatr Blood Cancer 2012; 59: 1180-1182. (c) 2012 Wiley Periodicals, Inc. PMID- 22302773 TI - Immunohistochemistry of angiogenesis mediators before and after pulsed dye laser treatment of angiomas. AB - BACKGROUND AND OBJECTIVE: Tissue effects of vascular lesion laser treatment are incompletely understood. Injury caused by pulsed dye laser (PDL) treatment may result in altered expression of mediators associated with angiogenesis. MATERIALS AND METHODS: Eight human subjects had one angioma treated with PDL (7 mm, 1.5 millisecond pulse duration, 9 J/cm(2), cryogen spray cooling of 30 millisecond with a 30 millisecond delay). One week later, three biopsies were taken: normal skin, untreated angioma, angioma post-PDL. Tissue was frozen and sections processed for immunohistochemistry staining of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), matrix metalloproteinase 9 (MMP 9), and angiopoietin 2 (ANG-2). Images were graded in a blinded fashion by a board certified dermatopathologist. RESULTS: There were no clear trends in VEGF expression in the epidermis, dermis, or endothelial cells. As compared to normal skin, angiomas demonstrated the following: bFGF was decreased in the epidermis; MMP-9 was decreased or unchanged in the epidermis and increased in the endothelial cells; ANG-2 was increased in the endothelial cells. When comparing normal skin to angiomas + PDL, bFGF was decreased in the epidermis and increased in the dermis; MMP-9 was decreased or unchanged in the epidermis; ANG-2 was again increased in the endothelial cells. Comparison of staining in angioma to angioma + PDL samples revealed increased dermal bFGF expression. CONCLUSION: Alterations in angiogenesis mediators were noted after PDL. Angiogenesis mediator changes associated with PDL treatment differed from those previously reported for incisional biopsies. This pilot study can guide future work on laser-induced alterations in vascular lesions and such information may ultimately be used to optimize treatment outcomes. PMID- 22302774 TI - Radiofrequency ablation vs bipolar umbilical cord coagulation in the management of complicated monochorionic pregnancies. AB - OBJECTIVE: The application of radiofrequency ablation (RFA) termination procedures to complicated cases involving monochorionic twins offers the potential of a less invasive option when compared to endoscopic techniques. The purpose of this study was to compare outcomes between these two techniques. METHODS: A retrospective review was undertaken of all cases of complicated monochorionic twin gestations treated at the Children's Hospital of Philadelphia from July 1996 to December 2010. Cases were identified from the fetal treatment database and data extracted in a uniform fashion from the patients' charts. RESULTS: A total of 149 cases were identified with procedures performed on 146. Indications for selective termination of one fetus were twin reversed arterial perfusion sequence in 53, severe twin-to-twin transfusion syndrome in 43, discordance for fetal anomalies in 26 and selective intrauterine growth restriction in 24. Eighty-eight cases were managed with bipolar cord coagulation (BCC) and 58 with RFA. The procedures in all cases were technically successful in achieving selective termination. The mean gestational age at the time of the procedure was 20.9 +/- 2.7 weeks in the BCC group vs 20.2 +/- 2.2 weeks in the RFA group (P = 0.1). The median gestational age at delivery was 34.7 (interquartile range (IQR), 29.2-38.6) weeks for the BCC group vs 33.0 (IQR, 23.4 38.9) weeks in the RFA group (P = 0.073). Mean birth weight did not differ between the two groups. The procedure-to-delivery time was 87.1 +/- 42.1 days for the BCC group vs 73.8 +/- 47.2 days for the RFA group (P = 0.1). Overall survival was 85.2% in the BCC group vs 70.7% in the RFA group (P = 0.014). This was attributed primarily to a survival rate of 10.5% in the RFA group compared with 31.6% in the BCC group for cases where delivery occurred before 28 weeks' gestation (P = 0.01). Premature rupture of the membranes occurred in 27.3% in the BCC group vs 13.7% in the RFA group (P = 0.05). Preterm labor was more common in the BCC group than in the RFA group (22.4 vs 7%, respectively; P = 0.009). CONCLUSION: Despite the smaller caliber of the instrument, RFA is not associated with a decrease in the overall complication rate for selective termination procedures. The technique used for selective termination should still be determined by technical considerations but patients should be informed of the survival rate associated with each technique. PMID- 22302775 TI - A 2,6-disubstituted 4-anilinoquinazoline derivative facilitates cardiomyogenesis of embryonic stem cells. AB - Chemical approaches are widely used in directed differentiation of embryonic stem (ES) cells. In our search for novel lead compounds that could facilitate cardiomyogenesis of ES cells, we designed a two-step screening system based on P19 embryonic carcinoma and mouse ES cells. Application of this system to a quinazoline compound library including 2,3-disubstituted 8-arylamino-3H imidazo[4,5-g]quinazolines and 2,6-disubstituted 4-anilinoquinazoline led us to the discovery of compound 62, which exhibits a stable cardiomyogenic effect on both P19 and mouse ES cells at a concentration of 0.1 MUM. An EGFR inhibition assay and molecular docking studies confirmed 62 as a potent EGFR inhibitor with a tyrosine kinase IC(50) value of 101 nM. However, major differences in cardiomyogenic activity were observed between iressa and 62, indicating that other molecular events are also involved in compound 62-induced cardiomyogenesis of ES cells. PMID- 22302776 TI - Qualitative inquiry into women's menopause experiences in southeastern Iran. AB - Menopause is defined as amenorrhea for one year. Signs and symptoms are categorized as physical and psychological changes, including depression, hot flushes and ageing. Woman's responses to menopause are governed by lifestyle factors. The purpose of this study was to determine how Iranian women experience menopause and hormone therapy. A qualitative inquiry was conducted through semistructured, in-depth interviews to explore study questions in 11 menopausal women. Participants had positive and negative menopause experiences. Negative menopause experiences are due to severity of symptoms. Menopause can be facilitated by increasing women's knowledge about this phase and ways to cope with it. PMID- 22302777 TI - Pitfalls in diagnosis of uterine artery pseudoaneurysm after Cesarean section. PMID- 22302778 TI - Feasibility, reliability, and validity of the Pediatric Quality of Life Inventory TM generic core scales, cancer module, and multidimensional fatigue scale in long term adult survivors of pediatric cancer. AB - BACKGROUND: Most health-related quality of life assessments are designed for either children or adults and have not been evaluated for adolescent and young adult survivors of pediatric cancer. The objective of this study was to examine the feasibility, reliability, and validity of the Pediatric Quality of Life Inventory (PedsQL TM Generic Core Scales, Cancer Module, and Multidimensional Fatigue Scale in adult survivors of pediatric cancer. METHODS: Adult survivors (n = 64; Mean age 35 year old; >2 years after treatment) completed the PedsQLTM Generic Core Scales, Cancer Module, and Multidimensional Fatigue Scale. Feasibility was examined with floor and ceiling effects; and internal consistency was determined by Cronbach's coefficient alpha calculations. Inter-factor correlations were also assessed. RESULTS: Significant ceiling effects were observed for the scales of social function, nausea, procedural anxiety, treatment anxiety, and communication. Internal consistency for all subscales was within the recommended ranges (alpha >= 0.70). Moderate to strong correlations between most Cancer Module and Generic Core Scales (r = 0.25 to r = 0.76) and between the Multidimensional Fatigue Scale and Generic Core Scales (r = 0.37 to r = 0.73). CONCLUSIONS: The PedsQLTM Generic Core Scales, Cancer Module, and Multidimensional Fatigue Scale appear to be feasible for an older population of pediatric cancer survivors; however, some of the Cancer Module Scales (nausea, procedural/treatment anxiety, and communication) were deemed not relevant for long-term survivors. More information is needed to determine whether the issues addressed by these modules are meaningful to long-term adult survivors of pediatric cancers. PMID- 22302779 TI - A prescription for improving antibiotic prescribing in primary care. PMID- 22302781 TI - Cholestasis secondary to anabolic steroid use in young men. PMID- 22302780 TI - Effectiveness of multifaceted educational programme to reduce antibiotic dispensing in primary care: practice based randomised controlled trial. AB - OBJECTIVE: To evaluate the effectiveness and costs of a multifaceted flexible educational programme aimed at reducing antibiotic dispensing at the practice level in primary care. DESIGN: Randomised controlled trial with general practices as the unit of randomisation and analysis. Clinicians and researchers were blinded to group allocation until after randomisation. SETTING: 68 general practices with about 480,000 patients in Wales, United Kingdom. PARTICIPANTS: 34 practices were randomised to receive the educational programme and 34 practices to be controls. 139 clinicians from the intervention practices and 124 from control practices had agreed to participate before randomisation. Practice level data covering all the clinicians in the 68 practices were analysed. INTERVENTIONS: Intervention practices followed the Stemming the Tide of Antibiotic Resistance (STAR) educational programme, which included a practice based seminar reflecting on the practices' own dispensing and resistance data, online educational elements, and practising consulting skills in routine care. Control practices provided usual care. MAIN OUTCOME MEASURES: Total numbers of oral antibiotic items dispensed for all causes per 1000 practice patients in the year after the intervention, adjusted for the previous year's dispensing. Secondary outcomes included reconsultations, admissions to hospital for selected causes, and costs. RESULTS: The rate of oral antibiotic dispensing (items per 1000 registered patients) decreased by 14.1 in the intervention group but increased by 12.1 in the control group, a net difference of 26.1. After adjustment for baseline dispensing rate, this amounted to a 4.2% (95% confidence interval 0.6% to 7.7%) reduction in total oral antibiotic dispensing for the year in the intervention group relative to the control group (P=0.02). Reductions were found for all classes of antibiotics other than penicillinase-resistant penicillins but were largest and significant individually for phenoxymethylpenicillins (penicillin V) (7.3%, 0.4% to 13.7%) and macrolides (7.7%, 1.1% to 13.8%). There were no significant differences between intervention and control practices in the number of admissions to hospital or in reconsultations for a respiratory tract infection within seven days of an index consultation. The mean cost of the programme was L2923 (?3491, $4572) per practice (SD L1187). There was a 5.5% reduction in the cost of dispensed antibiotics in the intervention group compared with the control group (-0.4% to 11.4%), equivalent to a reduction of about L830 a year for an average intervention practice. CONCLUSION: The STAR educational programme led to reductions in all cause oral antibiotic dispensing over the subsequent year with no significant change in admissions to hospital, reconsultations, or costs. Trial registration ISRCT No 63355948. PMID- 22302782 TI - Rare combination of exomphalos with umbilical cord teratoma. PMID- 22302783 TI - Gemcitabine and docetaxel (GEMDOX) for the treatment of relapsed and refractory pediatric sarcomas. AB - BACKGROUND: Patients with relapsed pediatric sarcomas have a poor outcome and are in need of novel effective therapies. METHODS: We retrospectively reviewed the records of patients at Children's Healthcare of Atlanta who were treated with gemcitabine (675 mg/m(2)) intravenously (IV) on Day 1 and Day 8, and docetaxel (75 mg/m(2)) IV on Day 8, repeated every 3 weeks. RESULTS: Nineteen patients with a median age of 11 years were treated from 2006-2010 and received 123 total courses. Two patients (11%), both with rhabdomyosarcoma, demonstrated objectives responses [one complete response (CR) and one partial response (PR)]. Seven other patients (39%) had stable disease (SD). The 1-year progression-free survival (PFS) of the entire cohort was 24% +/- 10% with a median time to progression of 2 months (range: 0.5-14 months). The 1-year overall survival (OS) was 43% +/- 11%. Grade 3 or 4 toxicities occurred in 14 patients (74%) and 52 courses (42%), and were most commonly hematologic (neutropenia = 37, anemia = 17, and thrombocytopenia = 23 courses). CONCLUSIONS: The dismal outcomes for patients with relapsed and refractory sarcomas and the lack of effective sarcoma salvage regimens highlight the need for new approaches. This report of the therapeutic activity of gemcitabine and docetaxel (GEMDOX) in rhabdomyosarcoma and other pediatric reports describing activity in osteosarcoma and Ewing sarcoma suggest that this combination should be considered for formal evaluation in a pediatric specific clinical trial. At a minimum, it appears to offer a reasonable, tolerable, palliative option. PMID- 22302784 TI - [Health service costs in people with severe mental illness: patient report vs. administrative records]. AB - OBJECTIVE: During the last years, self-reported measures of mental health service use for people with mental illness have become increasingly popular. Yet, little is known about the differences between patient report and administrative records and how these may be explained. METHODS: 82 of the 294 participants of the study "Outcome monitoring and outcome management in in-patient psychiatric care" were insured with a major statutory health insurance (AOK Schwaben) and gave informed consent to researchers to access their AOK administrative records. For a 6-month period prior to psychiatric hospital admission, these were compared to the costs as assessed via the German version of the "Client Sociodemographic and Service Receipt Inventory" (CSSRI-EU). RESULTS: Median total monthly treatment costs were 112.23 ? (patient-reported) vs. 254.23 ? (administrative records; paired Wilcoxon Z = - 3.75; p < 0.001). Cost differences were independent of participants' socioeconomic and clinical characteristics. Correspondence between total treatment costs was substantial for total costs (rho = 0.48; p < 0.001) and all subtypes of costs (in- and outpatient services, medication). CONCLUSIONS: Despite a general tendency to underreport service use, self-report data adequately reflect the "real" health service costs as evident in the health insurance records of people with mental illness. PMID- 22302785 TI - Hyperphosphorylation of the cardiac ryanodine receptor at serine 2808 is not involved in cardiac dysfunction after myocardial infarction. AB - RATIONALE: Abnormal behavior of the cardiac ryanodine receptor (RyR2) has been linked to cardiac arrhythmias and heart failure (HF) after myocardial infarction (MI). It has been proposed that protein kinase A (PKA) hyperphosphorylation of the RyR2 at a single residue, Ser-2808, is a critical mediator of RyR dysfunction, depressed cardiac performance, and HF after MI. OBJECTIVE: We used a mouse model (RyRS2808A) in which PKA hyperphosphorylation of the RyR2 at Ser-2808 is prevented to determine whether loss of PKA phosphorylation at this site averts post MI cardiac pump dysfunction. METHODS AND RESULTS: MI was induced in wild type (WT) and S2808A mice. Myocyte and cardiac function were compared in WT and S2808A animals before and after MI. The effects of the PKA activator Isoproterenol (Iso) on L-type Ca(2+) current (I(CaL)), contractions, and [Ca(2+)](I) transients were also measured. Both WT and S2808A mice had depressed pump function after MI, and there were no differences between groups. MI size was also identical in both groups. L type Ca(2+) current, contractions, Ca(2+) transients, and SR Ca(2+) load were also not significantly different in WT versus S2808A myocytes either before or after MI. Iso effects on Ca(2+) current, contraction, Ca(2+) transients, and SR Ca(2+) load were identical in WT and S2808A myocytes before and after MI at both low and high concentrations. CONCLUSIONS: These results strongly support the idea that PKA phosphorylation of RyR-S2808 is irrelevant to the development of cardiac dysfunction after MI, at least in the mice used in this study. PMID- 22302786 TI - The IL-17A/IL-17RA axis plays a proatherogenic role via the regulation of aortic myeloid cell recruitment. AB - RATIONALE: Atherosclerosis is a disease of large- and medium-sized arteries that is characterized by chronic vascular inflammation. While the role of Th1, Th2, and T-regulatory subsets in atherogenesis is established, the involvement of IL 17A-producing cells remains unclear. OBJECTIVE: To investigate the role of the IL 17A/IL-17RA axis in atherosclerosis. METHODS AND RESULTS: We bred apolipoprotein E-deficient (Apoe(-/-)) mice with IL-17A-deficient and IL-17 receptor A-deficient mice to generate Il17a(-/-)Apoe(-/-) and Il17ra(-/-)Apoe(-/-) mice. Western diet fed Il17a(-/-)Apoe(-/-) and Il17ra(-/-)Apoe(-/-) mice had smaller atherosclerotic plaques in the aortic arch and aortic roots, but showed little difference in plaque burden in the thoracoabdominal aorta in comparison with Apoe(-/-) controls. Flow cytometric analysis of Il17a(-/-)Apoe(-/-) and Il17ra(-/-)Apoe(-/ ) aortas revealed that deficiency of IL-17A/IL-17RA preferentially reduced aortic arch, but not thoracoabdominal aortic T cell, neutrophil, and macrophage content in comparison with Apoe(-/-) aortic segments. In contrast to ubiquitous IL-17RA expression throughout the aorta, IL-17A was preferentially expressed within the aortic arch of WD-fed Apoe(-/-) mice. Deficiency of IL-17A or IL-17RA reduced aortic arch, but not thoracoabdominal aortic TNFalpha and CXCL2 expression. Aortic vascular IL-17RA supports monocyte adherence to explanted aortas in ex vivo adhesion assays. Short-term homing experiments revealed that the recruitment of adoptively transferred monocytes and neutrophils to the aortas of Il17ra(-/ )Apoe(-/-) mice is impaired in comparison with Apoe(-/-) recipients. CONCLUSIONS: The IL-17A/IL-17RA axis increases aortic arch inflammation during atherogenesis through the induction of aortic chemokines, and the acceleration of neutrophil and monocyte recruitment to this site. PMID- 22302787 TI - A caveolae-targeted L-type Ca2+ channel antagonist inhibits hypertrophic signaling without reducing cardiac contractility. AB - RATIONALE: The source of Ca(2+) to activate pathological cardiac hypertrophy is not clearly defined. Ca(2+) influx through the L-type Ca(2+) channels (LTCCs) determines "contractile" Ca(2+), which is not thought to be the source of "hypertrophic" Ca(2+). However, some LTCCs are housed in caveolin-3 (Cav-3) enriched signaling microdomains and are not directly involved in contraction. The function of these LTCCs is unknown. OBJECTIVE: To test the idea that LTCCs in Cav 3-containing signaling domains are a source of Ca(2+) to activate the calcineurin nuclear factor of activated T-cell signaling cascade that promotes pathological hypertrophy. METHODS AND RESULTS: We developed reagents that targeted Ca(2+) channel-blocking Rem proteins to Cav-3-containing membranes, which house a small fraction of cardiac LTCCs. Blocking LTCCs within this Cav-3 membrane domain eliminated a small fraction of the LTCC current and almost all of the Ca(2+) influx-induced NFAT nuclear translocation, but it did not reduce myocyte contractility. CONCLUSIONS: We provide proof of concept that Ca(2+) influx through LTCCs within caveolae signaling domains can activate "hypertrophic" signaling, and this Ca(2+) influx can be selectively blocked without reducing cardiac contractility. PMID- 22302789 TI - Different tests for a difference: how do we do research? PMID- 22302788 TI - Ephrin-B1 is a novel specific component of the lateral membrane of the cardiomyocyte and is essential for the stability of cardiac tissue architecture cohesion. AB - RATIONALE: Cardiac tissue cohesion relying on highly ordered cardiomyocytes (CM) interactions is critical because most cardiomyopathies are associated with tissue remodeling and architecture alterations. OBJECTIVE: Eph/ephrin system constitutes a ubiquitous system coordinating cellular communications which recently emerged as a major regulator in adult organs. We examined if eph/ephrin could participate in cardiac tissue cyto-organization. METHODS AND RESULTS: We reported the expression of cardiac ephrin-B1 in both endothelial cells and for the first time in CMs where ephrin-B1 localized specifically at the lateral membrane. Ephrin-B1 knock-out (KO) mice progressively developed cardiac tissue disorganization with loss of adult CM rod-shape and sarcomeric and intercalated disk structural disorganization confirmed in CM-specific ephrin-B1 KO mice. CMs lateral membrane exhibited abnormal structure by electron microscopy and notably increased stiffness by atomic force microscopy. In wild-type CMs, ephrin-B1 interacted with claudin-5/ZO-1 complex at the lateral membrane, whereas the complex disappeared in KO/CM-specific ephrin-B1 KO mice. Ephrin-B1 deficiency resulted in decreased mRNA expression of CM basement membrane components and disorganized fibrillar collagen matrix, independently of classical integrin/dystroglycan system. KO/CM specific ephrin-B1 KO mice exhibited increased left ventricle diameter and delayed atrioventricular conduction. Under pressure overload stress, KO mice were prone to death and exhibited striking tissue disorganization. Finally, failing CMs displayed downregulated ephrin-B1/claudin-5 gene expression linearly related to the ejection fraction. CONCLUSIONS: Ephrin-B1 is necessary for cardiac tissue architecture cohesion by stabilizing the adult CM morphology through regulation of its lateral membrane. Because decreased ephrin-B1 is associated with molecular/functional cardiac defects, it could represent a new actor in the transition toward heart failure. PMID- 22302790 TI - The anoctamin (TMEM16) gene family: calcium-activated chloride channels come of age. PMID- 22302791 TI - Muscles bring breathing alive. PMID- 22302792 TI - Phleboliths from venous malformations of the head and neck. AB - OBJECTIVES/HYPOTHESIS: Phleboliths in venous malformations (VM) of the head and neck are often observed and may cause significant symptoms. Only a few articles refer to the morphology and composition of the phleboliths in VM. The objective of this study was to analyse and to demonstrate their composition and morphology. METHODS: Patients with VM presenting to a vascular anomalies centre during a three-year period were identified. The incidence of phleboliths was analysed followed by morphological and structural analysis with cone beam tomography and X ray diffraction. RESULTS: Phleboliths were identified in 28/98 patients with VM of the head and neck. Seven patients underwent conventional surgery to reduce the volume of the VM or to remove the phleboliths, which were localized in the cheek (3 cases), submandibular region (2 cases), infrahyoidal neck or upper eyelid (1 case each). The structural analysis showed that more advanced lamination and an increasing radiopacity of the cortex was observed in larger phleboliths. X-ray powder diffraction analysis revealed that the main constituent in the pulverized phleboliths was carbonate-fluorohydroxylapatite. CONCLUSION: This study shows in a vivid way that phleboliths from VM of the head and neck area show a laminar structure and consist of apatite, without any indication of differences in their chemical composition. Treatment of localized intravascular coagulopathy in VM might be able to prevent the formation and the progression of phleboliths. Hypothetically, another option might be lithotripsy. PMID- 22302793 TI - Right axillosubclavian vein thrombosis resolved by percutaneous rheolytic thrombectomy in a patient with a recurrent gastrointestinal stromal tumour undergoing imatinib mesylate treatment. AB - The manifestation and management of spontaneous axillosubclavian vein thrombosis in patients with gastrointestinal stromal tumour (GIST) undergoing oral chemotherapy have never been described. We report a patient with a recurrent GIST who was receiving maintenance imatinib yet developed a right axillosubclavian vein thrombotic occlusion. The occluded vein was unresponsive to systemic anticoagulation but was reopened by percutaneous rheolytic thrombectomy and has shown good long-term patency. Thus, for patients with recurrent GIST undergoing imatinib therapy, axillosubclavian vein thrombosis might manifest as a complication and could be managed with rheolytic thrombectomy, which thoroughly removes intravascular thrombus and effectively re-vascularizes the thrombosed vessel uneventfully. PMID- 22302794 TI - Using interocular suppression and EEG to study semantic processing. PMID- 22302795 TI - The nucleosome remodeling and deacetylase chromatin remodeling (NuRD) complex is required for peripheral nerve myelination. AB - Several key transcription factors and coregulators important to peripheral nerve myelination have been identified, but the contributions of specific chromatin remodeling complexes to peripheral nerve myelination have not been analyzed. Chromodomain helicase DNA-binding protein 4 (Chd4) is the core catalytic subunit of the nucleosome remodeling and deacetylase (NuRD) chromatin remodeling complex. Previous studies have shown Chd4 interacts with Nab (NGFI-A/Egr-binding) corepressors, which are required for early growth response 2 (Egr2/Krox20), to direct peripheral nerve myelination by Schwann cells. In this study, we examined the developmental importance of the NuRD complex in peripheral nerve myelination through the generation of conditional Chd4 knock-out mice in Schwann cells (Chd4(loxP/loxP); P0-cre). Chd4 conditional null mice were found to have delayed myelination, radial sorting defects, hypomyelination, and the persistence of promyelinating Schwann cells. Loss of Chd4 leads to elevated expression of immature Schwann cell genes (Id2, c-Jun, and p75), and sustained expression of the promyelinating Schwann cell gene, Oct6/Scip, without affecting the levels of Egr2/Krox20. Furthermore, Schwann cell proliferation is upregulated in Chd4-null sciatic nerve. In vivo chromatin immunoprecipitation studies reveal recruitment of Chd4 and another NuRD component, Mta2, to genes that are positively and negatively regulated by Egr2 during myelination. Together, these results underscore the necessity of Chd4 function to guide proper terminal differentiation of Schwann cells and implicate the NuRD chromatin remodeling complex as a requisite factor in timely and stable peripheral nerve myelination. PMID- 22302796 TI - Neuronal glutamate transporters regulate glial excitatory transmission. AB - In the CNS, excitatory amino acid transporters (EAATs) localized to neurons and glia terminate the actions of synaptically released glutamate. Whereas glial transporters are primarily responsible for maintaining low ambient levels of extracellular glutamate, neuronal transporters have additional roles in shaping excitatory synaptic transmission. Here we test the hypothesis that the expression level of the Purkinje cell (PC)-specific transporter, EAAT4, near parallel fiber (PF) release sites controls the extrasynaptic glutamate concentration transient following synaptic stimulation. Expression of EAAT4 follows a parasagittal banding pattern that allows us to compare regions of high and low EAAT4 expressing PCs. Using EAAT4 promoter-driven eGFP reporter mice together with pharmacology and genetic deletion, we show that the level of neuronal transporter expression influences extrasynaptic transmission from PFs to adjacent Bergmann glia (BG). Surprisingly, a twofold difference in functional EAAT4 levels is sufficient to alter signaling to BG, although EAAT4 may only be responsible for removing a fraction of released glutamate. These results demonstrate that physiological regulation of neuronal transporter expression can alter extrasynaptic neuroglial signaling. PMID- 22302797 TI - Mimicking phosphorylation at serine 87 inhibits the aggregation of human alpha synuclein and protects against its toxicity in a rat model of Parkinson's disease. AB - Several lines of evidence suggest that phosphorylation of alpha-synuclein (alpha syn) at S87 or S129 may play an important role in regulating its aggregation, fibrillogenesis, Lewy body formation, and neurotoxicity in vivo. However, whether phosphorylation at these residues enhances or protects against alpha-syn toxicity in vivo remains unknown. In this study, we investigated the cellular and behavioral effect of overexpression of wild-type (WT), S87A, and S87E alpha-syn to block or to mimic S87 phosphorylation, respectively, in the substantia nigra of Wistar rats using recombinant adeno-associated vectors. Our results revealed that WT and S87A overexpression induced alpha-syn aggregation, loss of dopaminergic neurons, and fiber pathology. These neuropathological effects correlated well with the induction of hemi-parkinsonian motor symptoms. Strikingly, overexpression of the phosphomimic mutant S87E did not show any toxic effect on dopaminergic neurons and resulted in significantly less alpha-syn aggregates, dystrophic fibers, and motor impairment. Together, our data demonstrate, for the first time, that mimicking phosphorylation at S87 inhibits alpha-syn aggregation and protects against alpha-syn-induced toxicity in vivo, suggesting that phosphorylation at this residue would play an important role in controlling alpha-syn neuropathology. In addition, our results provide strong evidence for a direct correlation between alpha-syn-induced neurotoxicity, fiber pathology, and motor impairment and the extent of alpha-syn aggregation in vivo, suggesting that lowering alpha-syn levels and/or blocking its aggregation are viable therapeutic strategies for the treatment of Parkinson's disease and related synucleinopathies. PMID- 22302798 TI - Inflammatory effects of highly pathogenic H5N1 influenza virus infection in the CNS of mice. AB - The A/VN/1203/04 strain of the H5N1 influenza virus is capable of infecting the CNS of mice and inducing a number of neurodegenerative pathologies. Here, we examined the effects of H5N1 on several pathological aspects affected in parkinsonism, including loss of the phenotype of dopaminergic neurons located in the substantia nigra pars compacta (SNpc), expression of monoamines and indolamines in brain, alterations in SNpc microglia number and morphology, and expression of cytokines, chemokines, and growth factors. We find that H5N1 induces a transient loss of the dopaminergic phenotype in SNpc and now report that this loss recovers by 90 d after infection. A similar pattern of loss and recovery was seen in monoamine levels of the basal ganglia. The inflammatory response in lung and different regions of the brain known to be targets of the H5N1 virus (brainstem, substantia nigra, striatum, and cortex) were examined at 3, 10, 21, 60, and 90 d after infection. In each of these brain regions, we found a significant increase in the number of activated microglia that lasted at least 90 d. We also quantified expression of IL-1alpha, IL-1beta, IL-2, IL-6, IL-9, IL 10, IL-12(p70), IL-13, TNF-alpha, IFN-gamma, granulocyte-macrophage colony stimulating factor, granulocyte colony-stimulating factor, macrophage colony stimulating factor, eotaxin, interferon-inducible protein 10, cytokine-induced neutrophil chemoattractant, monocyte chemotactic protein-1, macrophage inflammatory protein (MIP) 1alpha, MIP-1beta, and VEGF, and found that the pattern and levels of expression are dependent on both brain region and time after infection. We conclude that H5N1 infection in mice induces a long-lasting inflammatory response in brain and may play a contributing factor in the development of pathologies in neurodegenerative disorders. PMID- 22302799 TI - Natural versus synthetic stimuli for estimating receptive field models: a comparison of predictive robustness. AB - An ultimate goal of visual neuroscience is to understand the neural encoding of complex, everyday scenes. Yet most of our knowledge of neuronal receptive fields has come from studies using simple artificial stimuli (e.g., bars, gratings) that may fail to reveal the full nature of a neuron's actual response properties. Our goal was to compare the utility of artificial and natural stimuli for estimating receptive field (RF) models. Using extracellular recordings from simple type cells in cat A18, we acquired responses to three types of broadband stimulus ensembles: two widely used artificial patterns (white noise and short bars), and natural images. We used a primary dataset to estimate the spatiotemporal receptive field (STRF) with two hold-back datasets for regularization and validation. STRFs were estimated using an iterative regression algorithm with regularization and subsequently fit with a zero-memory nonlinearity. Each RF model (STRF and zero-memory nonlinearity) was then used in simulations to predict responses to the same stimulus type used to estimate it, as well as to other broadband stimuli and sinewave gratings. White noise stimuli often elicited poor responses leading to noisy RF estimates, while short bars and natural image stimuli were more successful in driving A18 neurons and producing clear RF estimates with strong predictive ability. Natural image-derived RF models were the most robust at predicting responses to other broadband stimulus ensembles that were not used in their estimation and also provided good predictions of tuning curves for sinewave gratings. PMID- 22302800 TI - Differential DNA methylation patterns define status epilepticus and epileptic tolerance. AB - Prolonged seizures (status epilepticus) produce pathophysiological changes in the hippocampus that are associated with large-scale, wide-ranging changes in gene expression. Epileptic tolerance is an endogenous program of cell protection that can be activated in the brain by previous exposure to a non-harmful seizure episode before status epilepticus. A major transcriptional feature of tolerance is gene downregulation. Here, through methylation analysis of 34,143 discrete loci representing all annotated CpG islands and promoter regions in the mouse genome, we report the genome-wide DNA methylation changes in the hippocampus after status epilepticus and epileptic tolerance in adult mice. A total of 321 genes showed altered DNA methylation after status epilepticus alone or status epilepticus that followed seizure preconditioning, with >90% of the promoters of these genes undergoing hypomethylation. These profiles included genes not previously associated with epilepsy, such as the polycomb gene Phc2. Differential methylation events generally occurred throughout the genome without bias for a particular chromosomal region, with the exception of a small region of chromosome 4, which was significantly overrepresented with genes hypomethylated after status epilepticus. Surprisingly, only few genes displayed differential hypermethylation in epileptic tolerance. Nevertheless, gene ontology analysis emphasized the majority of differential methylation events between the groups occurred in genes associated with nuclear functions, such as DNA binding and transcriptional regulation. The present study reports select, genome-wide DNA methylation changes after status epilepticus and in epileptic tolerance, which may contribute to regulating the gene expression environment of the seizure-damaged hippocampus. PMID- 22302801 TI - Changing microcircuits in the subplate of the developing cortex. AB - Subplate neurons (SPNs) are a population of neurons in the mammalian cerebral cortex that exist predominantly in the prenatal and early postnatal period. Loss of SPNs prevents the functional maturation of the cerebral cortex. SPNs receive subcortical input from the thalamus and relay this information to the developing cortical plate and thereby can influence cortical activity in a feedforward manner. Little is known about potential feedback projections from the cortical plate to SPNs. Thus, we investigated the spatial distribution of intracortical synaptic inputs to SPNs in vitro in mouse auditory cortex by photostimulation. We find that SPNs fell into two broad classes based on their distinct spatial patterns of synaptic inputs. The first class of SPNs receives inputs from only deep cortical layers, while the second class of SPNs receives inputs from deep as well as superficial layers including layer 4. We find that superficial cortical inputs to SPNs emerge in the second postnatal week and that SPNs that receive superficial cortical input are located more superficially than those that do not. Our data thus suggest that distinct circuits are present in the subplate and that, while SPNs participate in an early feedforward circuit, they are also involved in a feedback circuit at older ages. Together, our results show that SPNs are tightly integrated into the developing thalamocortical and intracortical circuit. The feedback projections from the cortical plate might enable SPNs to amplify thalamic inputs to SPNs. PMID- 22302802 TI - LRRK2 inhibition attenuates microglial inflammatory responses. AB - Missense mutations in leucine-rich repeat kinase 2 (LRRK2) cause late-onset Parkinson's disease (PD), and common genetic variation in LRRK2 modifies susceptibility to Crohn's disease and leprosy. High levels of LRRK2 expression in peripheral monocytes and macrophages suggest a role for LRRK2 in these cells, yet little is known about LRRK2 expression and function in immune cells of the brain. Here, we demonstrate a role for LRRK2 in mediating microglial proinflammatory responses and morphology. In a murine model of neuroinflammation, we observe robust induction of LRRK2 in microglia. Experiments with toll-like receptor 4 (TLR4)-stimulated rat primary microglia show that inflammation increases LRRK2 activity and expression, while inhibition of LRRK2 kinase activity or knockdown of protein attenuates TNFalpha secretion and nitric oxide synthase (iNOS) induction. LRRK2 inhibition blocks TLR4 stimulated microglial process outgrowth and impairs ADP stimulated microglial chemotaxis. However, actin inhibitors that phenocopy inhibition of process outgrowth and chemotaxis fail to modify TLR4 stimulation of TNFalpha secretion and inducible iNOS induction, suggesting that LRRK2 acts upstream of cytoskeleton control as a stress-responsive kinase. These data demonstrate LRRK2 in regulating responses in immune cells of the brain and further implicate microglial involvement in late-onset PD. PMID- 22302803 TI - Organization of vomeronasal sensory coding revealed by fast volumetric calcium imaging. AB - A long-standing goal in neuroscience is to perform exhaustive recording of each neuron in a functional local circuit. To achieve this goal, one promising approach is optical imaging of fluorescent calcium indicators, but typically the tens or hundreds of cells imaged simultaneously comprise only a tiny percentage of the neurons in an intact circuit. Here, we show that a recent innovation, objective-coupled planar illumination (OCPI) microscopy, permits simultaneous recording from three-dimensional volumes containing many thousand neurons. We used OCPI microscopy to record chemosensory responses in the mouse vomeronasal epithelium, for which expression of hundreds of receptor types implies high functional diversity. The implications of this diversity for sensory coding were examined using several classes of previously reported vomeronasal ligands, including sulfated steroids. A collection of just 12 sulfated steroids activated more than a quarter of the neurons in the apical vomeronasal epithelium; unexpectedly, responses were functionally organized into a modest number of classes with characteristic spatial distribution. Recording from a whole sensory system thus revealed new organizational principles. PMID- 22302804 TI - 5-HT1A receptor-responsive pedunculopontine tegmental neurons suppress REM sleep and respiratory motor activity. AB - Serotonin type 1A (5-HT(1A)) receptor-responsive neurons in the pedunculopontine tegmental nucleus (PPTn) become maximally active immediately before and during rapid eye movement (REM) sleep. A prevailing model of REM sleep generation indicates that activation of such neurons contributes significantly to the generation of REM sleep, and if correct then inactivation of such neurons ought to suppress REM sleep. We test this hypothesis using bilateral microperfusion of the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 10 MUm) into the PPTn; this tool has been shown to selectively silence REM sleep active PPTn neurons while the activity of wake/REM sleep-active PPTn neurons is unaffected. Contrary to the prevailing model, bilateral microperfusion of 8-OH DPAT into the PPTn (n = 23 rats) significantly increased REM sleep both as a percentage of the total recording time and sleep time, compared with both within animal vehicle controls and between-animal time-controls. This increased REM sleep resulted from an increased frequency of REM sleep bouts but not their duration, indicating an effect on mechanisms of REM sleep initiation but not maintenance. Furthermore, an increased proportion of the REM sleep bouts stemmed from periods of low REM sleep drive quantified electrographically. Targeted suppression of 5-HT(1A) receptor-responsive PPTn neurons also increased respiratory rate and respiratory-related genioglossus activity, and increased the frequency and amplitude of the sporadic genioglossus activations occurring during REM sleep. These data indicate that 5-HT(1A) receptor-responsive PPTn neurons normally function to restrain REM sleep by elevating the drive threshold for REM sleep induction, and restrain the expression of respiratory rate and motor activities. PMID- 22302805 TI - Bimodal optomotor response to plaids in blowflies: mechanisms of component selectivity and evidence for pattern selectivity. AB - Many animals estimate their self-motion and the movement of external objects by exploiting panoramic patterns of visual motion. To probe how visual systems process compound motion patterns, superimposed visual gratings moving in different directions, plaid stimuli, have been successfully used in vertebrates. Surprisingly, nothing is known about how visually guided insects process plaids. Here, we explored in the blowfly how the well characterized yaw optomotor reflex and the activity of identified visual interneurons depend on plaid stimuli. We show that contrary to previous expectations, the yaw optomotor reflex shows a bimodal directional tuning for certain plaid stimuli. To understand the neural correlates of this behavior, we recorded the responses of a visual interneuron supporting the reflex, the H1 cell, which was also bimodally tuned to the plaid direction. Using a computational model, we identified the essential neural processing steps required to capture the observed response properties. These processing steps have functional parallels with mechanisms found in the primate visual system, despite different biophysical implementations. By characterizing other visual neurons supporting visually guided behaviors, we found responses that ranged from being bimodally tuned to the stimulus direction (component selective), to responses that appear to be tuned to the direction of the global pattern (pattern-selective). Our results extend the current understanding of neural mechanisms of motion processing in insects, and indicate that the fly employs a wider range of behavioral responses to multiple motion cues than previously reported. PMID- 22302806 TI - PTEN regulation of local and long-range connections in mouse auditory cortex. AB - Autism spectrum disorders (ASDs) are highly heritable developmental disorders caused by a heterogeneous collection of genetic lesions. Here we use a mouse model to study the effect on cortical connectivity of disrupting the ASD candidate gene PTEN (phosphatase and tensin homolog deleted on chromosome 10). Through Cre-mediated recombination, we conditionally knocked out PTEN expression in a subset of auditory cortical neurons. Analysis of long-range connectivity using channelrhodopsin-2 revealed that the strength of synaptic inputs from both the contralateral auditory cortex and from the thalamus onto PTEN-cko neurons was enhanced compared with nearby neurons with normal PTEN expression. Laser-scanning photostimulation showed that local inputs onto PTEN-cko neurons in the auditory cortex were similarly enhanced. The hyperconnectivity caused by PTEN-cko could be blocked by rapamycin, a specific inhibitor of the PTEN downstream molecule mammalian target of rapamycin complex 1. Together, our results suggest that local and long-range hyperconnectivity may constitute a physiological basis for the effects of mutations in PTEN and possibly other ASD candidate genes. PMID- 22302807 TI - Dynamic correlation between whisking and breathing rhythms in mice. AB - Sniffing, a high-frequency, highly rhythmic inhalation and exhalation of air through the nose, plays an important role in rodent olfaction. Similarly, whisking, the active rhythmic movement of whiskers, plays an important role in rodent tactile sensation. Rodents whisk and sniff during exploratory behavior to sample odorants and surfaces. Whisking is thought to be coordinated with sniffing and normal respiratory behavior, but the precise temporal relationships between these movements are not known. Here, using direct measurements of whisking and respiratory movements, we examined the strength and temporal dynamics of the correlation between large-amplitude whisker movements and respiratory rhythm in mice. Whisking movements were detected using an optical sensor, and respiration was monitored with a thermistor placed close to the nostril. Our measurements revealed that breathing and whisking movements were significantly correlated only when the whisking rhythm was <5 Hz. Only a fraction (~13%) of all large-amplitude whisker movements occurred during episodes of high-frequency (>5 Hz) respiration typically associated with sniffing. Our results show that that the rhythms of respiratory and whisking movements are correlated only during low-frequency whisking and respiration. High-frequency whisking and sniffing behaviors are not correlated. We conclude that whisking and respiratory rhythms are generated by independent pattern-generating mechanisms. PMID- 22302808 TI - Noise overexposure alters long-term somatosensory-auditory processing in the dorsal cochlear nucleus--possible basis for tinnitus-related hyperactivity? AB - The dorsal cochlear nucleus (DCN) is the first neural site of bimodal auditory somatosensory integration. Previous studies have shown that stimulation of somatosensory pathways results in immediate suppression or enhancement of subsequent acoustically evoked discharges. In the unimpaired auditory system suppression predominates. However, damage to the auditory input pathway leads to enhancement of excitatory somatosensory inputs to the cochlear nucleus, changing their effects on DCN neurons (Shore et al., 2008; Zeng et al., 2009). Given the well described connection between the somatosensory system and tinnitus in patients we sought to determine whether plastic changes in long-lasting bimodal somatosensory-auditory processing accompany tinnitus. Here we demonstrate for the first time in vivo long-term effects of somatosensory inputs on acoustically evoked discharges of DCN neurons in guinea pigs. The effects of trigeminal nucleus stimulation are compared between normal-hearing animals and animals overexposed with narrow band noise and behaviorally tested for tinnitus. The noise exposure resulted in a temporary threshold shift in auditory brainstem responses but a persistent increase in spontaneous and sound-evoked DCN unit firing rates and increased steepness of rate-level functions. Rate increases were especially prominent in buildup units. The long-term somatosensory enhancement of sound-evoked responses was strengthened while suppressive effects diminished in noise-exposed animals, especially those that developed tinnitus. Damage to the auditory nerve is postulated to trigger compensatory long-term synaptic plasticity of somatosensory inputs that might be an important underlying mechanism for tinnitus generation. PMID- 22302809 TI - Neuronal responses in the nucleus accumbens shell during sexual behavior in male rats. AB - Previous behavioral studies have indicated that the nucleus accumbens (NAc) shell of a male rat is involved in its sexual behavior; however, no previous studies have investigated neuronal activities in the male rat NAc shell during sexual behavior. To investigate this issue, we recorded single unit activities in the NAc shell of male rats during sexual behavior. Of 123 NAc shell neurons studied, 53, 47, and 40 neurons exhibited significantly changed firing rates at various times during intromission, genital auto-grooming, and sniffing of females, respectively. The two types of NAc shell neurons [putative fast spiking interneurons (pFSIs) and medium spiny neurons (pMSNs)] responded differently during sexual behavior. First, more pFSIs than pMSNs exhibited inhibitory responses to thrusting with intromission and genital grooming, while pFSIs and pMSNs responded similarly to sniffing of females. Second, both pFSIs and pMSNs responded differently to thrusting with and without intromission. Furthermore, NAc shell neuronal activity was significantly different across the different phases of sexual behavior, and the number of NAc shell neurons with delta oscillation, which is related to behavioral inhibition, and high gamma oscillation, which is related to reward perception, increased after ejaculation. Together, our results suggest that the NAc shell is deeply involved in sexual behavior, and changes in NAc shell neuronal activity are related to performance of sexual behavior, encoding cues or contexts related to sexual behavior, reward related processing, and the inhibition of sexual behavior after ejaculation. PMID- 22302810 TI - Astrocytes control the development of the migration-promoting vasculature scaffold in the postnatal brain via VEGF signaling. AB - New neurons are constantly being generated in the postnatal subventricular zone. They have to migrate long distances via the rostral migratory stream (RMS) to reach their final destination in the olfactory bulb (OB). In adults, these neuronal precursors migrate in chains, ensheathed by astrocytic processes, and travel toward the OB along blood vessels (BVs) that topographically outline the RMS. The molecular and cellular mechanisms leading to the development of the RMS and the formation of the migration-promoting vasculature scaffold in the adult mice remain unclear. We now reveal that astrocytes orchestrate the formation and structural reorganization of the vasculature scaffold in the RMS and, during early developmental stages, the RMS contains only a few BVs oriented randomly with respect to the migrating neuroblasts. The first parallel BVs appeared at the outer border of the RMS, where vascular endothelial growth factor (VEGF) expressing astrocytes are located. Gain-of-function and loss-of-function experiments revealed that astrocyte-derived VEGF plays a crucial role in the formation and growth of new BVs. Real-time videoimaging also showed that the migration of neuronal precursors in the developing RMS differs substantially from neuronal displacement in the adult migratory stream partially because of not yet fully developed vasculature scaffold. The downregulation of VEGF in vivo, specifically in the astrocytes of the developing RMS, affected the development of the vasculature scaffold and led to alterations in neuroblast migration. Altogether, our results demonstrate that astrocytes orchestrate the formation and growth of parallel BVs, crucial migration-promoting scaffolds in the adult migratory stream, via VEGF signaling. PMID- 22302811 TI - Contrast-enhanced magnetic resonance microangiography reveals remodeling of the cerebral microvasculature in transgenic ArcAbeta mice. AB - Amyloid-beta (Abeta) deposition in the cerebral vasculature is accompanied by remodeling which has a profound influence on vascular integrity and function. In the current study we have quantitatively assessed the age-dependent changes of the cortical vasculature in the arcAbeta model of cerebral amyloidosis. To estimate the density of the cortical microvasculature in vivo, we used contrast enhanced magnetic resonance microangiography (CE-MUMRA). Three-dimensional gradient echo datasets with 60 MUm isotropic resolution were acquired in 4- and 24-month-old arcAbeta mice and compared with wild-type (wt) control mice of the same age before and after administration of superparamagnetic iron oxide nanoparticles. After segmentation of the cortical vasculature from difference images, an automated algorithm was applied for assessing the number and size distribution of intracortical vessels. With CE-MUMRA, cerebral arteries and veins with a diameter of less than the nominal pixel resolution (60 MUm) can be visualized. A significant age-dependent reduction in the number of functional intracortical microvessels (radii of 20-80 MUm) has been observed in 24-month-old arcAbeta mice compared with age-matched wt mice, whereas there was no difference between transgenic and wt mice of 4 months of age. Immunohistochemistry demonstrated strong fibrinogen and Abeta deposition in small- and medium-sized vessels, but not in large cerebral arteries, of 24-month-old arcAbeta mice. The reduced density of transcortical vessels may thus be attributed to impaired perfusion and vascular occlusion caused by deposition of Abeta and fibrin. The study demonstrated that remodeling of the cerebrovasculature can be monitored noninvasively with CE-MUMRA in mice. PMID- 22302812 TI - Novel GalphaS-protein signaling associated with membrane-tethered amyloid precursor protein intracellular domain. AB - Numerous physiological functions, including a role as a cell surface receptor, have been ascribed to Alzheimer's disease-associated amyloid precursor protein (APP). However, detailed analysis of intracellular signaling mediated by APP in neurons has been lacking. Here, we characterized intrinsic signaling associated with membrane-bound APP C-terminal fragments, which are generated following APP ectodomain release by alpha- or beta-secretase cleavage. We found that accumulation of APP C-terminal fragments or expression of membrane-tethered APP intracellular domain results in adenylate cyclase-dependent activation of PKA (protein kinase A) and inhibition of GSK3beta signaling cascades, and enhancement of axodendritic arborization in rat immortalized hippocampal neurons, mouse primary cortical neurons, and mouse neuroblastoma. We discovered an interaction between BBXXB motif of APP intracellular domain and the heterotrimeric G-protein subunit Galpha(S), and demonstrate that Galpha(S) coupling to adenylate cyclase mediates membrane-tethered APP intracellular domain-induced neurite outgrowth. Our study provides clear evidence that APP intracellular domain can have a nontranscriptional role in regulating neurite outgrowth through its membrane association. The novel functional coupling of membrane-bound APP C-terminal fragments with Galpha(S) signaling identified in this study could impact several brain functions such as synaptic plasticity and memory formation. PMID- 22302813 TI - Differentiated participation of thalamocortical subnetworks in slow/spindle waves and desynchronization. AB - During sleep, the electroencephalogram exhibits synchronized slow waves that desynchronize when animals awaken [desynchronized states (DSs)]. During slow-wave states, the membrane potentials of cortical neurons oscillate between discrete depolarized states ("Up states") and periods of hyperpolarization ("Down states"). To determine the role of corticothalamic loops in generating Up/Down oscillations in rats, we recorded unit activities of layer 5 (L5) corticothalamic (CTh) cells in the frontal cortex, neurons in the thalamic reticular nucleus, and basal ganglia- and cerebellum-linked thalamic relay nuclei, while simultaneously monitoring the local cortical field potential to identify slow-wave/spindle oscillations and desynchronization. We found that (1) some basal ganglia-linked and reticular thalamic cells fire preferentially near the beginning of Up states; (2) thalamic cells fire more selectively at a given Up-state phase than do CTh cells; (3) CTh and thalamic cells exhibit different action potential timings within spindle cycles; and (4) neurons exhibit different firing characteristics when comparing their activity during Up states and DSs. These data demonstrate that cortico-thalamo-cortical subnetworks are temporally differentiated during slow and spindle oscillations, that the basal ganglia-linked thalamic nuclei are closely related with Up-state initiation, and that Up states and DSs are distinguished as different depolarization states of neurons within the network. PMID- 22302814 TI - Psychophysiological analyses demonstrate the importance of neural envelope coding for speech perception in noise. AB - Understanding speech in noisy environments is often taken for granted; however, this task is particularly challenging for people with cochlear hearing loss, even with hearing aids or cochlear implants. A significant limitation to improving auditory prostheses is our lack of understanding of the neural basis for robust speech perception in noise. Perceptual studies suggest the slowly varying component of the acoustic waveform (envelope, ENV) is sufficient for understanding speech in quiet, but the rapidly varying temporal fine structure (TFS) is important in noise. These perceptual findings have important implications for cochlear implants, which currently only provide ENV; however, neural correlates have been difficult to evaluate due to cochlear transformations between acoustic TFS and recovered neural ENV. Here, we demonstrate the relative contributions of neural ENV and TFS by quantitatively linking neural coding, predicted from a computational auditory nerve model, with perception of vocoded speech in noise measured from normal hearing human listeners. Regression models with ENV and TFS coding as independent variables predicted speech identification and phonetic feature reception at both positive and negative signal-to-noise ratios. We found that: (1) neural ENV coding was a primary contributor to speech perception, even in noise; and (2) neural TFS contributed in noise mainly in the presence of neural ENV, but rarely as the primary cue itself. These results suggest that neural TFS has less perceptual salience than previously thought due to cochlear signal processing transformations between TFS and ENV. Because these transformations differ between normal and impaired ears, these findings have important translational implications for auditory prostheses. PMID- 22302815 TI - The loop diuretic bumetanide blocks posttraumatic p75NTR upregulation and rescues injured neurons. AB - Injured neurons become dependent on trophic factors for survival. However, application of trophic factors to the site of injury is technically extremely challenging. Novel approaches are needed to circumvent this problem. Here, we unravel the mechanism of the emergence of dependency of injured neurons on brain derived neurotrophic factor (BDNF) for survival. Based on this mechanism, we propose the use of the diuretic bumetanide to prevent the requirement for BDNF and consequent neuronal death in the injured areas. Responses to the neurotransmitter GABA change from hyperpolarizing in intact neurons to depolarizing in injured neurons. We show in vivo in rats and ex vivo in mouse organotypic slice cultures that posttraumatic GABA(A)-mediated depolarization is a cause for the well known phenomenon of pathological upregulation of pan neurotrophin receptor p75(NTR). The increase in intracellular Ca(2+) triggered by GABA-mediated depolarization activates ROCK (Rho kinase), which in turn leads to the upregulation of p75(NTR). We further show that high levels of p75(NTR) and its interaction with sortilin and proNGF set the dependency on BDNF for survival. Thus, application of bumetanide prevents p75(NTR) upregulation and neuronal death in the injured areas with reduced levels of endogenous BDNF. PMID- 22302816 TI - Generation of multiple classes of V0 neurons in zebrafish spinal cord: progenitor heterogeneity and temporal control of neuronal diversity. AB - The developing spinal cord is subdivided into distinct progenitor domains, each of which gives rise to different types of neurons. However, the developmental mechanisms responsible for generating neuronal diversity within a domain are not well understood. Here, we have studied zebrafish V0 neurons, those that derive from the p0 progenitor domain, to address this question. We find that all V0 neurons have commissural axons, but they can be divided into excitatory and inhibitory classes. V0 excitatory neurons (V0-e) can be further categorized into three groups based on their axonal trajectories; V0-eA (ascending), V0-eB (bifurcating), and V0-eD (descending) neurons. By using time-lapse imaging of p0 progenitors and their progeny, we show that inhibitory and excitatory neurons are produced from different progenitors. We also demonstrate that V0-eA neurons are produced from distinct progenitors, while V0-eB and V0-eD neurons are produced from common progenitors. We then use birth-date analysis to reveal that V0-eA, V0 eB, and V0-eD neurons arise in this order. By perturbing Notch signaling and accelerating neuronal differentiation, we predictably alter the generation of early born V0-e neurons at the expense of later born ones. These results suggest that multiple types of V0 neurons are produced by two distinct mechanisms; from heterogeneous p0 progenitors and from the same p0 progenitor, but in a time dependent manner. PMID- 22302817 TI - Neural correlates of humor detection and appreciation in children. AB - Humor is a vital component of human well-being. Neuroimaging studies conducted with adults indicate that humor activates specific brain regions, including the temporo-occipito-parietal junction (TOPJ), involved in incongruity resolution, and mesolimbic regions, involved in reward processing. However, no study to date has used neuroimaging to examine humor in typically developing children. Here, we illuminate the neural network involved in the detection and appreciation of humor in childhood. Fifteen typically developing children (ages, 6-12 years) were invited to watch and respond to video clips while neural activity was imaged with a 3T GE Discovery MR750 scanner. Before presentation during functional imaging, the clips were evaluated by age-matched controls and were representative of three categories: Funny, Positive (enjoyable but not funny), and Neutral (not intended to evoke any emotional response). We found TOPJ and mesolimbic activation in children's response to humor, suggesting these regions may form a humor-essential neural network already present in childhood. Furthermore, in a novel comparison of Funny to Positive stimuli, we found that bilateral TOPJ activation may be specific to humor processing and not part of a general constellation of neural activity in response to reward. Finally, we observed greater activation in the inferior frontal gyrus and nucleus accumbens in younger participants, indicating humor activation intensity changes during development. By providing a crucial link in studying the neurodevelopment of humor processing across the lifespan, our findings contribute valuable information about the evolution of how children understand their world. PMID- 22302818 TI - Internalized timing of isochronous sounds is represented in neuromagnetic beta oscillations. AB - Moving in synchrony with an auditory rhythm requires predictive action based on neurodynamic representation of temporal information. Although it is known that a regular auditory rhythm can facilitate rhythmic movement, the neural mechanisms underlying this phenomenon remain poorly understood. In this experiment using human magnetoencephalography, 12 young healthy adults listened passively to an isochronous auditory rhythm without producing rhythmic movement. We hypothesized that the dynamics of neuromagnetic beta-band oscillations (~20 Hz)-which are known to reflect changes in an active status of sensorimotor functions-would show modulations in both power and phase-coherence related to the rate of the auditory rhythm across both auditory and motor systems. Despite the absence of an intention to move, modulation of beta amplitude as well as changes in cortico cortical coherence followed the tempo of sound stimulation in auditory cortices and motor-related areas including the sensorimotor cortex, inferior-frontal gyrus, supplementary motor area, and the cerebellum. The time course of beta decrease after stimulus onset was consistent regardless of the rate or regularity of the stimulus, but the time course of the following beta rebound depended on the stimulus rate only in the regular stimulus conditions such that the beta amplitude reached its maximum just before the occurrence of the next sound. Our results suggest that the time course of beta modulation provides a mechanism for maintaining predictive timing, that beta oscillations reflect functional coordination between auditory and motor systems, and that coherence in beta oscillations dynamically configure the sensorimotor networks for auditory-motor coupling. PMID- 22302819 TI - A TrkB small molecule partial agonist rescues TrkB phosphorylation deficits and improves respiratory function in a mouse model of Rett syndrome. AB - Rett syndrome (RTT) results from loss-of-function mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2) and is characterized by abnormal motor, respiratory and autonomic control, cognitive impairment, autistic-like behaviors and increased risk of seizures. RTT patients and Mecp2-null mice exhibit reduced expression of brain-derived neurotrophic factor (BDNF), which has been linked in mice to increased respiratory frequency, a hallmark of RTT. The present study was undertaken to test the hypotheses that BDNF deficits in Mecp2 mutants are associated with reduced activation of the BDNF receptor, TrkB, and that pharmacologic activation of TrkB would improve respiratory function. We characterized BDNF protein expression, TrkB activation and respiration in heterozygous female Mecp2 mutant mice (Het), a model that recapitulates the somatic mosaicism for mutant MECP2 found in typical RTT patients, and evaluated the ability of a small molecule TrkB agonist, LM22A-4, to ameliorate biochemical and functional abnormalities in these animals. We found that Het mice exhibit (1) reduced BDNF expression and TrkB activation in the medulla and pons and (2) breathing dysfunction, characterized by increased frequency due to periods of tachypnea, and increased apneas, as in RTT patients. Treatment of Het mice with LM22A-4 for 4 weeks rescued wild-type levels of TrkB phosphorylation in the medulla and pons and restored wild-type breathing frequency. These data provide new insight into the role of BDNF signaling deficits in the pathophysiology of RTT and highlight TrkB as a possible therapeutic target in this disease. PMID- 22302820 TI - Increased excitability of somatosensory cortex in aged humans is associated with impaired tactile acuity. AB - Aging affects all levels of neural processing, including changes of intracortical inhibition and cortical excitability. Paired-pulse stimulation, the application of two stimuli in close succession, is a useful tool to investigate cortical excitability in humans. The paired-pulse behavior is characterized by the second response being significantly suppressed at short stimulus onset asynchronies. While in rat somatosensory cortex, intracortical inhibition has been demonstrated to decline with increasing age, data from human motor cortex of elderly subjects are controversial and there are no data for the human somatosensory cortex (SI). Moreover, behavioral implications of age-related changes of cortical excitability remain elusive. We therefore assessed SI excitability by combining paired-pulse median nerve stimulation with recording somatosensory evoked potentials in 138 healthy subjects aged 17-86 years. We found that paired-pulse suppression was characterized by substantial interindividual variability, but declined significantly with age, confirming reduced intracortical inhibition in elderly subjects. To link the age-related increase of cortical excitability to perceptual changes, we measured tactile two-point discrimination in a subsample of 26 aged participants who showed either low or high paired-pulse suppression. We found that tactile performance was particularly impaired in subjects showing markedly enhanced cortical excitability. Our data demonstrate that paired-pulse suppression of human SI is significantly reduced in older adults, and that age related enhancement of cortical excitability correlates with degradation of tactile perception. These findings indicate that cortical excitability constitutes an important mechanism that links age-related neurophysiological changes to behavioral alterations in humans. PMID- 22302822 TI - JNK1 inhibits GluR1 expression and GluR1-mediated calcium influx through phosphorylation and stabilization of Hes-1. AB - The GluR1 subunit of the AMPA receptor plays an important role in excitatory synaptic transmission and synaptic plasticity in the brain, but the regulation mechanism for GluR1 expression is largely unknown. Hairy and enhancer of split 1 (Hes-1) is a mammalian transcription repressor that regulates neuronal differentiation and development, but the role of Hes-1 in differentiated neurons is also less known. Here, we examined the molecular mechanism in regulation of GluR1 expression in rat cultured cortical neurons. We found that Hes-1 suppressed GluR1 promoter activity and decreased GluR1 expression through direct binding to the N-box and through preventing Mash1/E47 from binding to the E-box of GluR1 promoter. We also found that Hes-1 could be regulated by c-Jun N-terminal kinase (JNK1). JNK1 directly phosphorylates Hes-1 at Ser-263. Furthermore, JNK1 phosphorylation of Hes-1 stabilized the Hes-1 protein and enhanced the suppressing effect of Hes-1 on GluR1 expression. These effects were demonstrated both in the soma and at the synapse. Moreover, this JNK1-mediated signaling pathway was found to inhibit AMPA-evoked calcium influx in cortical neurons and this regulation mechanism is Notch independent. Here, we provided the first evidence that Hes-1 plays an important role in synaptic function in differentiated neurons. We also identified a novel JNK1-Hes-1 signaling pathway that regulates GluR1 expression involved in synaptic function in rat cortical neurons. PMID- 22302821 TI - Arrest of myelination and reduced axon growth when Schwann cells lack mTOR. AB - In developing peripheral nerves, differentiating Schwann cells sort individual axons from bundles and ensheath them to generate multiple layers of myelin. In recent years, there has been an increased understanding of the extracellular and intracellular factors that initiate and stimulate Schwann cell myelination, together with a growing appreciation of some of the signaling pathways involved. However, our knowledge of how Schwann cell growth is regulated during myelination is still incomplete. The mammalian target of rapamycin (mTOR) is a core kinase in two major complexes, mTORC1 and mTORC2, that regulate cell growth and differentiation in a variety of mammalian cells. Here we show that elimination of mTOR from murine Schwann cells prevented neither radial sorting nor the initiation of myelination. However, normal postnatal growth of myelinating Schwann cells, both radially and longitudinally, was highly retarded. The myelin sheath in the mutant was much thinner than normal; nevertheless, sheath thickness relative to axon diameter (g-ratio) remained constant in both wild-type and mutant nerves from P14 to P90. Although axon diameters were normal in the mutant at the initiation of myelination, further growth as myelination proceeded was retarded, and this was associated with reduced phosphorylation of neurofilaments. Consistent with thinner axonal diameters and internodal lengths, conduction velocities in mutant quadriceps nerves were also reduced. These data establish a critical role for mTOR signaling in both the longitudinal and radial growth of the myelinating Schwann cell. PMID- 22302823 TI - Calpains are downstream effectors of bax-dependent excitotoxic apoptosis. AB - Excitotoxicity resulting from excessive Ca(2+) influx through glutamate receptors contributes to neuronal injury after stroke, trauma, and seizures. Increased cytosolic Ca(2+) levels activate a family of calcium-dependent proteases with papain-like activity, the calpains. Here we investigated the role of calpain activation during NMDA-induced excitotoxic injury in embryonic (E16-E18) murine cortical neurons that (1) underwent excitotoxic necrosis, characterized by immediate deregulation of Ca(2+) homeostasis, a persistent depolarization of mitochondrial membrane potential (Deltapsi(m)), and insensitivity to bax-gene deletion, (2) underwent excitotoxic apoptosis, characterized by recovery of NMDA induced cytosolic Ca(2+) increases, sensitivity to bax gene deletion, and delayed Deltapsi(m) depolarization and Ca(2+) deregulation, or (3) that were tolerant to excitotoxic injury. Interestingly, treatment with the calpain inhibitor calpeptin, overexpression of the endogenous calpain inhibitor calpastatin, or gene silencing of calpain protected neurons against excitotoxic apoptosis but did not influence excitotoxic necrosis. Calpeptin failed to exert a protective effect in bax-deficient neurons but protected bid-deficient neurons similarly to wild type cells. To identify when calpains became activated during excitotoxic apoptosis, we monitored calpain activation dynamics by time-lapse fluorescence microscopy using a calpain-sensitive Forster resonance energy transfer probe. We observed a delayed calpain activation that occurred downstream of mitochondrial engagement and directly preceded neuronal death. In contrast, we could not detect significant calpain activity during excitotoxic necrosis or in neurons that were tolerant to excitotoxic injury. Oxygen/glucose deprivation-induced injury in organotypic hippocampal slice cultures confirmed that calpains were specifically activated during bax-dependent apoptosis and in this setting function as downstream cell-death executioners. PMID- 22302824 TI - Electrical brain stimulation improves cognitive performance by modulating functional connectivity and task-specific activation. AB - Excitatory anodal transcranial direct current stimulation (atDCS) can improve human cognitive functions, but neural underpinnings of its mode of action remain elusive. In a cross-over placebo ("sham") controlled study we used functional magnetic resonance imaging (fMRI) to investigate neurofunctional correlates of improved language functions induced by atDCS over a core language area, the left inferior frontal gyrus (IFG). Intrascanner transcranial direct current stimulation-induced changes in overt semantic word generation assessed behavioral modulation; task-related and task-independent (resting-state) fMRI characterized language network changes. Improved word-retrieval during atDCS was paralleled by selectively reduced task-related activation in the left ventral IFG, an area specifically implicated in semantic retrieval processes. Under atDCS, resting state fMRI revealed increased connectivity of the left IFG and additional major hubs overlapping with the language network. In conclusion, atDCS modulates endogenous low-frequency oscillations in a distributed set of functionally connected brain areas, possibly inducing more efficient processing in critical task-relevant areas and improved behavioral performance. PMID- 22302825 TI - Independent vesicle pools underlie different modes of release during neuronal development. AB - Mature presynaptic terminals release neurotransmitter both in response to activity and spontaneously. We found that axons of rat hippocampal neurons initially show very high levels of exclusively spontaneous release, which progressively switches over to the mature phenotype during synapse formation. These two modes of vesicle cycling derive from distinct pools throughout development and the initiation of activity-dependent release was independent of postsynaptic contacts, suggesting it is an autonomous presynaptic event. PMID- 22302826 TI - MU- and delta-opioid-related processes in the accumbens core and shell differentially mediate the influence of reward-guided and stimulus-guided decisions on choice. AB - Two motivational processes affect choice between actions: (1) changes in the reward value of the goal or outcome of an action and (2) changes in the predicted value of an action based on outcome-related stimuli. Here, we evaluated the role of MU-opioid receptor (MOR) and delta-opioid receptor (DOR) in the nucleus accumbens in the way these motivational processes influence choice using outcome revaluation and pavlovian-instrumental transfer tests. We first examined the effect of genetic deletion of MOR and DOR in specific knock-out mice. We then assessed the effect of infusing the MOR antagonist d-Phe-Cys-Tyr-D-Trp-Arg-Thr Pen-Thr-NH(2) (CTAP) or the DOR antagonist naltrindole into the core or shell subregions of the nucleus accumbens on these tests in rats. We found that, whereas MOR knock-outs showed normal transfer, they failed to show a selective outcome revaluation effect. Conversely, DOR knock-outs showed normal revaluation but were insensitive to the influence of outcome-related cues on choice. This double dissociation was also found regionally within the nucleus accumbens in rats. Infusion of naltrindole into the accumbens shell abolished transfer but had no effect on outcome revaluation and did not influence either effect when infused into the accumbens core. Conversely, infusion of CTAP into the accumbens core abolished sensitivity to outcome revaluation but had no effect on transfer and did not influence either effect when infused into the accumbens shell. These results suggest that reward-based and stimulus-based values exert distinct motivational influences on choice that can be doubly dissociated both neuroanatomically and neurochemically at the level of the nucleus accumbens. PMID- 22302828 TI - Specialized cortical subnetworks differentially connect frontal cortex to parahippocampal areas. AB - How information is manipulated and segregated within local circuits in the frontal cortex remains mysterious, in part because of inadequate knowledge regarding the connectivity of diverse pyramidal cell subtypes. The frontal cortex participates in the formation and retrieval of declarative memories through projections to the perirhinal cortex, and in procedural learning through projections to the striatum/pontine nuclei. In rat frontal cortex, we identified two pyramidal cell subtypes selectively projecting to distinct subregions of perirhinal cortex (PRC). PRC-projecting cells in upper layer 2/3 (L2/3) of the frontal cortex projected to perirhinal area 35, while neurons in L5 innervated perirhinal area 36. L2/3 PRC-projecting cells partially overlapped with those projecting to the basolateral amygdala. L5 PRC-projecting cells partially overlapped with crossed corticostriatal cells, but were distinct from neighboring corticothalamic (CTh)/corticopontine cells. L5 PRC-projecting and CTh cells were different in their electrophysiological properties and dendritic/axonal morphologies. Within the frontal cortex, L2/3 PRC-projecting cells innervated L5 PRC-projecting and CTh cells with similar probabilities, but received feedback excitation only from PRC-projecting cells. These data suggest that specific neuron subtypes in different cortical layers are reciprocally excited via interlaminar loops. Thus, two interacting output channels send information from the frontal cortex to different hierarchical stages of the parahippocampal network, areas 35 and 36, with additional collaterals selectively targeting the amygdala or basal ganglia, respectively. Combined with the hierarchical connectivity of PRC-projecting and CTh cells, these observations demonstrate an exquisite diversification of frontal projection neurons selectively connected according to their participation in distinct memory subsystems. PMID- 22302827 TI - Gene coexpression networks in human brain identify epigenetic modifications in alcohol dependence. AB - Alcohol abuse causes widespread changes in gene expression in human brain, some of which contribute to alcohol dependence. Previous microarray studies identified individual genes as candidates for alcohol phenotypes, but efforts to generate an integrated view of molecular and cellular changes underlying alcohol addiction are lacking. Here, we applied a novel systems approach to transcriptome profiling in postmortem human brains and generated a systemic view of brain alterations associated with alcohol abuse. We identified critical cellular components and previously unrecognized epigenetic determinants of gene coexpression relationships and discovered novel markers of chromatin modifications in alcoholic brain. Higher expression levels of endogenous retroviruses and genes with high GC content in alcoholics were associated with DNA hypomethylation and increased histone H3K4 trimethylation, suggesting a critical role of epigenetic mechanisms in alcohol addiction. Analysis of cell-type-specific transcriptomes revealed remarkable consistency between molecular profiles and cellular abnormalities in alcoholic brain. Based on evidence from this study and others, we generated a systems hypothesis for the central role of chromatin modifications in alcohol dependence that integrates epigenetic regulation of gene expression with pathophysiological and neuroadaptive changes in alcoholic brain. Our results offer implications for epigenetic therapeutics in alcohol and drug addiction. PMID- 22302829 TI - Successful reduction of clinical relevant neovascularization with a modified crossectomy combined with a barrier technique after 10-year follow-up. AB - OBJECTIVE: The aim of this retrospective study was to assess the long-term results of stripping the insufficient great saphenous vein (GSV) with stump coagulation, closure of the cribriform fascia and some additional measures, which will be described in detail. METHODS: Patients treated from 1998 to 1999 for varicose veins had been invited in 2009 for follow-up colour-coded duplex sonography and had been asked to answer a quality-of-life questionnaire. In 2009, the examinations for the study were conducted at a clinic of angiology by an independent and experienced sonographer. RESULTS: From a total of 165 patients, 91 (136 limbs) had been willing to participate in the study. Duplex ultrasound after a mean follow-up of 10.7 years revealed only clinically non-relevant (? < 0.3 cm) neovascularizations in 1.5% of all treated legs. No clinical relevant varicosities from the groin had developed. CONCLUSION: The crossectomy combined with stump coagulation and suture of the fossa ovalis, completed with some additional measures, is a successful method to reduce neovascularization and recurrent varicosities, even for redo-crossectomies, without increasing the risk of perioperative complications. PMID- 22302830 TI - Nutrient deprivation regulates DNA damage repair in cardiomyocytes via loss of the base-excision repair enzyme OGG1. AB - Oxidative stress contributes to the pathogenesis of many diseases, including heart failure, but the role and regulation of oxidative DNA damage in many cases have not been studied. Here, we set out to examine how oxidative DNA damage is regulated in cardiomyocytes. Compared to normal healthy controls, human hearts in end-stage cardiomyopathy (EsCM) showed a high degree of DNA damage by histological evidence of damage markers, including 8-oxoG and gammaH2AX (8-oxoG: 4.7+/-0.88 vs. 99.9+/-0.11%; gammaH2AX: 2.1+/-0.33 vs. 85.0+/-13.8%; P<0.01) This raised the possibility that defective DNA repair may be partly responsible. Indeed, nutrient deprivation led to impaired base-excision repair (BER) in cardiomyocytes in vitro, accompanied by loss of the BER enzyme OGG1, while BER activity was rescued by recombinant OGG1 (control vs. nutrient deprived vs. nutrient deprived+OGG1; 100+/-2.96 vs. 68.2+/-7.53 vs. 94.0+/-0.72%; ANOVA, P<0.01). Hearts from humans with EsCM and two murine models of myocardial stress also showed a loss of OGG1 protein. OGG1 loss was inhibited by the autophagy inhibitor bafilomycin and in autophagy-deficient Atg5(-/-) mouse embryonic fibroblasts. However, pharmacological activation of autophagy, itself, did not induce OGG1 loss, suggesting that autophagy is necessary but not sufficient for OGG1 turnover, and OGG1 loss requires concurrent nutrient deprivation. Finally, we found that the role of autophagy in nutrient starvation is complex, since it balanced the positive effects of ROS inhibition against the negative effect of OGG1 loss. Therefore, we have identified a central role for OGG1 in regulating DNA repair in cardiomyopathy. The manipulation of OGG1 may be used in future studies to examine the direct contribution of oxidative DNA damage to the progression of heart failure. PMID- 22302832 TI - Synthesis and preliminary evaluation of 18F-labeled pyridaben analogues for myocardial perfusion imaging with PET. AB - In this study the (18)F-labeled pyridaben analogs 2-tertbutyl-4-chloro-5-(4-(2 (18)F-fluoroethoxy))benzyloxy-2H-pyridazin-3-one ((18)F-FP1OP) and 2-tertbutyl-4 chloro-5-(4-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy))benzyloxy-2H-pyridazin-3 one ((18)F-FP3OP) were synthesized, characterized, and evaluated as potential myocardial perfusion imaging (MPI) agents with PET. METHODS: The tosylate labeling precursors of 2-tert-butyl-4-chloro-5-(4-(2-tosyloxy-ethoxy))-benzyloxy 2H-pyridazin-3-one (OTs-P1OP), 2-tert-butyl-4-chloro-5-(4-(2-(2-(2-tosyloxy ethoxy)ethoxy)ethoxy))-benzyloxy-2H-pyridazin-3-one (OTs-P3OP), and the corresponding nonradioactive compounds ((19)F-FP1OP and (19)F-FP3OP) were synthesized and characterized by infrared, (1)H nuclear magnetic resonance, (13)C nuclear magnetic resonance, and mass spectrometry analysis. (18)F-FP1OP and (18)F FP3OP were obtained by 1-step nucleophilic substitution of tosyl with (18)F and evaluated as MPI agents in vitro (physicochemical properties, stability), ex vivo (autoradiography), and in vivo (toxicity and biodistribution in normal mice; cardiac PET in healthy Chinese mini swine and in acute myocardial infarction and chronic myocardial ischemia models). RESULTS: The total radiosynthesis time of both tracers, including final high-pressure liquid chromatography purification, was about 70-90 min. Typical decay-corrected radiochemical yields were about 50%, and the radiochemical purities were more than 98% after purification. (18)F-FP1OP had lower hydrophilicity and higher water stability than that of (18)F-FP3OP. In biodistribution studies, both (18)F-FP1OP and (18)F-FP3OP had high heart uptake (31.13 +/- 6.24 and 31.10 +/- 3.72 percentage injected dose per gram at 2 min after injection, respectively) and high heart-to-liver, heart-to-lung, and heart to-blood ratios at all time points after injection. Further autoradiography evaluation of (18)F-FP1OP showed that the heart uptake could be blocked effectively by rotenone or nonradioactive (19)F-FP1OP. Clear cardiac PET images of (18)F-FP1OP were obtained in healthy Chinese mini swine at 2, 15, 30, 60, and 120 min after injection, and the uptake of perfusion deficit areas was much lower than in normal tissue in both acute myocardial infarction and chronic myocardial ischemia models. CONCLUSION: The (18)F-labeled pyridaben analogs reported in this study have high heart uptake and low background uptake in both the mouse model and the Chinese mini swine model. The tracer with the shorter radiolabeling side chain ((18)F-FP1OP) has better stability, faster clearance from the major organs, and a higher heart-to-liver ratio than the other tracer ((18)F-FP3OP). On the basis of the promising biologic properties, this mitochondrial complex I-targeted tracer ((18)F-FP1OP) is worthy to be developed as an MPI agent and to be compared with the other PET MPI agents in the future. PMID- 22302831 TI - Interferon-gamma biphasically regulates angiotensinogen expression via a JAK-STAT pathway and suppressor of cytokine signaling 1 (SOCS1) in renal proximal tubular cells. AB - Renal inflammation modulates angiotensinogen (AGT) production in renal proximal tubular cells (RPTCs) via inflammatory cytokines, including interleukin-6, tumor necrosis factor alpha, and interferon-gamma (IFN-gamma). Among these, the effects of IFN-gamma on AGT regulation in RPTCs are incompletely delineated. This study aimed to elucidate mechanisms by which IFN-gamma regulates AGT expression in RPTCs. RPTCs were incubated with or without IFN-gamma up to 48 h. AGT expression, STAT1 and STAT3 activities, and SOCS1 expression were evaluated. RNA interference studies against STAT1, SOCS1, and STAT3 were performed to elucidate a signaling cascade. IFN-gamma decreased AGT expression at 6 h (0.61+/-0.05, ratio to control) and 12 h (0.47+/-0.03). In contrast, longer exposure for 24 and 48 h increased AGT expression (1.76+/-0.18, EC(50)=3.4 ng/ml, and 1.45+/-0.08, respectively). IFN-gamma treatment for 6 h strongly induced STAT1 phosphorylation and SOCS1 augmentation, and decreased STAT3 activity. However, STAT1 phosphorylation and SOCS1 augmentation waned at 24 h, while STAT3 activity increased. RNA interference studies revealed that activation of STAT1-SOCS1 axis decreased STAT3 activity. Thus, IFN-gamma biphasically regulates AGT expression in RPTCs via STAT3 activity modulated by STAT1-SOCS1 axis, suggesting the STAT1 SOCS1 axis is important in IFN-gamma-induced activation of the intrarenal renin angiotensin system. PMID- 22302833 TI - A 43 year old woman with a 40 year history of exertional chest pain. PMID- 22302834 TI - Fall in suicides among mental health patients linked to improvements in mental health services. PMID- 22302835 TI - US board says censuring research on avian flu was necessary to prevent a potential catastrophe. PMID- 22302836 TI - "Golden Pill" award remains unfilled for the fourth year running. PMID- 22302837 TI - Private firm launches 16 point transformation plan for failing NHS hospital. PMID- 22302838 TI - Blockade of the nuclear factor-kappaB pathway in the endothelium prevents insulin resistance and prolongs life spans. AB - BACKGROUND: Nuclear factor-kappaB (NF-kappaB) signaling plays critical roles in physiological and pathological processes such as responses to inflammation and oxidative stress. METHODS AND RESULTS: To examine the role of endothelial NF kappaB signaling in vivo, we generated transgenic mice expressing dominant negative IkappaB under the Tie2 promoter/enhancer (E-DNIkappaB mice). These mice exhibited functional inhibition of NF-kappaB signaling specifically in endothelial cells. Although E-DNIkappaB mice displayed no overt phenotypic changes when young and lean, they were protected from the development of insulin resistance associated with obesity, whether diet- or genetics-induced. Obesity induced macrophage infiltration into adipose tissue and plasma oxidative stress markers were decreased and blood flow and mitochondrial content in muscle and active-phase locomotor activity were increased in E-DNIkappaB mice. In addition to inhibition of obesity-related metabolic deteriorations, blockade of endothelial NF-kappaB signaling prevented age-related insulin resistance and vascular senescence and, notably, prolonged life span. These antiaging phenotypes were also associated with decreased oxidative stress markers, increased muscle blood flow, enhanced active-phase locomotor activity, and aortic upregulation of mitochondrial sirtuin-related proteins. CONCLUSIONS: The endothelium plays important roles in obesity- and age-related disorders through intracellular NF kappaB signaling, thereby ultimately affecting life span. Endothelial NF-kappaB signaling is a potential target for treating the metabolic syndrome and for antiaging strategies. PMID- 22302839 TI - Endothelial nuclear factor kappaB in obesity and aging: is endothelial nuclear factor kappaB a master regulator of inflammation and insulin resistance? PMID- 22302840 TI - Very late coronary stent thrombosis of a newer-generation everolimus-eluting stent compared with early-generation drug-eluting stents: a prospective cohort study. AB - BACKGROUND: Early-generation drug-eluting stents releasing sirolimus (SES) or paclitaxel (PES) are associated with increased risk of very late stent thrombosis occurring >1 year after stent implantation. It is unknown whether the risk of very late stent thrombosis persists with newer-generation everolimus-eluting stents (EES). METHODS AND RESULTS: We assessed the risk of stent thrombosis in a cohort of 12 339 patients with unrestricted use of drug-eluting stents (3819 SES, 4308 PES, 4212 EES). Results are incidence rates per 100 person-years after inverse probability of treatment weighting to adjust for group differences. During follow-up of up to 4 years, the overall incidence rate of definite stent thrombosis was lower with EES (1.4 per 100 person-years) compared with SES (2.9; hazard ratio, 0.41; 95% confidence interval, 0.27-0.62; P<0.0001) and PES (4.4; hazard ratio, 0.33; 95% confidence interval, 0.23-0.48; P<0.0001). The incidence rate per 100 person-years of early (0-30 days), late (31 days-1 year), and very late stent thrombosis amounted to 0.6, 0.1, and 0.6 among EES-treated patients; 1.0, 0.3, and 1.6 among SES-treated patients; and 1.3, 0.7, and 2.4 among PES treated patients. Differences in favor of EES were most pronounced beyond 1 year, with a hazard ratio of 0.33 (EES versus SES; P=0.006) and 0.34 (EES versus PES; P<0.0001). There was a lower risk of cardiac death or myocardial with EES compared with PES (hazard ratio, 0.65; 95% confidence interval, 0.56-0.75; P<0.0001), which was directly related to the lower risk of stent thrombosis associated events (EES versus PES: hazard ratio, 0.36; 95% confidence interval, 0.23-0.57). CONCLUSION: Current treatment with EES is associated with a lower risk of very late stent thrombosis compared with early-generation drug-eluting stents. PMID- 22302841 TI - Evidence of safety and effectiveness for a drug-eluting stent: how should we respond this time? PMID- 22302842 TI - Goal-directed behavior under emotional distraction is preserved by enhanced task specific activation. AB - Despite the distracting effects of emotional stimuli on concurrent task performance, humans are able to uphold goal-directed behavior. Here, we investigated the hypothesis that this effect is due to the enhanced recruitment of task-specific neural resources. In a two-step functional magnetic resonance imaging study, we first localized those areas involved in mental arithmetics by contrasting arithmetic problems with a number detection task. The resulting activation maps were then used as masks in a second experiment that compared the effects of neutral and emotional distracter images on mental arithmetics. We found increased response times in the emotional distracter condition, accompanied by enhanced activation in task-specific areas, including superior parietal cortex, dorsolateral and dorsomedial prefrontal cortex. This activation increase correlated with larger behavioral impairment through emotional distraction. Similar error rates in both conditions indicate that cognitive task performance is preserved through enhanced recruitment of task-specific neural resources when emotional distracter stimuli are present. PMID- 22302843 TI - Developmental changes in mu suppression to observed and executed actions in autism spectrum disorders. AB - There has been debate over whether disruptions in the mirror neuron system (MNS) play a key role in the core social deficits observed in autism spectrum disorders (ASD). EEG mu suppression during the observation of biological actions is believed to reflect MNS functioning, but understanding of the developmental progression of the MNS and EEG mu rhythm in both typical and atypical development is lacking. To provide a more thorough and direct exploration of the development of mu suppression in individuals with ASD, a sample of 66 individuals with ASD and 51 typically developing individuals of 6-17 years old were pooled from four previously published studies employing similar EEG methodology. We found a significant correlation between age and mu suppression in response to the observation of actions, both for individuals with ASD and typical individuals. This relationship was not seen during the execution of actions. Additionally, the strength of the correlation during the observation of actions did not significantly differ between groups. The results provide evidence against the argument that mirror neuron dysfunction improves with age in individuals with ASD and suggest, instead, that a diagnosis-independent developmental change may be at the root of the correlation of age and mu suppression. PMID- 22302844 TI - Leptospirosis after typhoon. AB - Leptospirosis is a zoonotic disease with protean manifestations. A 35-year-old male presented with pneumonia after the Typhoon Morakot. Skin rash, conjunctival suffusion, and subconjunctival hemorrhage led us to the diagnosis of leptospirosis and the microscopic agglutination test confirmed the diagnosis. This patient well demonstrated the picture of conjunctival suffusion and reminded us of the alertness of leptospirosis after a typhoon. PMID- 22302845 TI - Recommendations for publication of viral genetic data and sample access for novel viruses and strains. PMID- 22302846 TI - How do we best diagnose malaria in Africa? PMID- 22302847 TI - False-negative rapid diagnostic tests for malaria and deletion of the histidine rich repeat region of the hrp2 gene. AB - We identified 480 persons with positive thick smears for asexual Plasmodium falciparum parasites, of whom 454 had positive rapid diagnostic tests (RDTs) for the histidine-rich protein 2 (HRP2) product of the hrp2 gene and 26 had negative tests. Polymerase chain reaction (PCR) amplification for the histidine-rich repeat region of that gene was negative in one-half (10/22) of false-negative specimens available, consistent with spontaneous deletion. False-negative RDTs were found only in persons with asymptomatic infections, and multiplicities of infection (MOIs) were lower in persons with false-negative RDTs (both P < 0.001). These results show that parasites that fail to produce HRP2 can cause patent bloodstream infections and false-negative RDT results. The importance of these observations is likely to increase as malaria control improves, because lower MOIs are associated with false-negative RDTs and false-negative RDTs are more frequent in persons with asymptomatic infections. These findings suggest that the use of HRP2-based RDTs should be reconsidered. PMID- 22302848 TI - Performance of two malaria rapid diagnostic tests in febrile adult patients with and without human immunodeficiency virus-1 infection in Blantyre, Malawi. AB - The performance of two histidine-rich protein type-2-based malaria rapid diagnostic tests (mRDTs) was examined in a rural area with a high prevalence of malaria and human immunodeficiency virus type-1 (HIV-1) infection in 113 and 445 febrile patients >= 15 years of age with and without HIV-1 infection, respectively. Patients were tested for HIV-1 infection by using a standard assay and for Plasmodium falciparum by using two mRDTs and microscopy. When microscopy was used as the gold standard, both mRDTs performed similarly in patients with and without HIV-1 infection: Bioline SD Malaria Antigen P.f, sensitivity 94.4% (95% confidence interval [CI]: 81.3-99.3%) versus 97.1% (95% CI:92.8-99.2%) and specificity 50.6% (95% CI: 39.0-62.2%) versus 47.2% (95% CI: 41.4-53.1%); and ICT diagnostics Malaria Pf, sensitivity 94.4% (95% CI: 81.3-99.3%) versus 97.1% (95% CI: 92.8-99.2%) and specificity 50.6% (95% CI:39.0-62.2%) versus 50.3% (95% CI: 44.4-56.1%). Infection with HIV-1 does not appear to affect the performance of these histidine-rich protein type-2 (HRP-2)-based mRDTs. PMID- 22302849 TI - Compliance, safety, and effectiveness of fixed-dose artesunate-amodiaquine for presumptive treatment of non-severe malaria in the context of home management of malaria in Madagascar. AB - Home management of malaria is recommended for prompt, effective antimalarial treatment in children less than five years of age. Compliance, safety, and effectiveness of the new fixed-dose artesunate-amodiaquine regimen used to treat suspected malaria were assessed in febrile children enrolled in a 24-month cohort study in two settings in Madagascar. Children with fever were asked to visit community health workers. Presumptive antimalarial treatment was given and further visits were scheduled for follow-up. The primary endpoint was the risk of clinical/parasitologic treatment failure. Secondary outcomes included fever/parasite clearance, change in hemoglobin levels, and frequency of adverse events. The global clinical cure rate was 98.4% by day 28 and 97.9% by day 42. Reported compliance was 83.4%. No severe adverse effects were observed. This study provides comprehensive data concerning the clinical cure rate obtained with artesunate-amodiaquine and evidence supporting the scaling up of home management of malaria. PMID- 22302850 TI - Different patterns of pfcrt and pfmdr1 polymorphisms in P. falciparum isolates from Nigeria and Brazil: the potential role of antimalarial drug selection pressure. AB - The effect of antimalarial drug selection on pfcrt and pfmdr1 polymorphisms in Plasmodium falciparum isolates from two distinct geographical locations was determined in 70 and 18 P. falciparum isolates from Nigeria and Brazil, respectively, using nested polymerase chain reaction and direct DNA sequencing approaches. All isolates from Brazil and 72% from Nigeria harbored the mutant SVMNT and CVIET pfcrt haplotype, respectively. The pfcrt CVMNT haplotype was also observed in (7%) of the Nigerian samples. One hundred percent (100%) and 54% of the parasites from Brazil and Nigeria, respectively, harbored wild-type pfmdr1Asn86. We provide first evidence of emergence of the CVMNT haplotype in West Africa. The high prevalence of pfcrt CVIET and SVMNT haplotypes in Nigeria and Brazil, respectively, is indicative of different selective pressure by chloroquine and amodiaquine. Continuous monitoring of pfcrt SVMNT haplotype is required in endemic areas of Africa, where artesunate-amodiaquine combination is used for treatment of acute uncomplicated malaria. PMID- 22302851 TI - Systemic antibody responses to the immunodominant p23 antigen and p23 polymorphisms in children with cryptosporidiosis in Bangladesh. AB - Cryptosporidium is a major cause of diarrhea in children in developing countries. However, there is no vaccine available and little is known about immune responses to protective antigens. We investigated antibody responses to p23, a putative vaccine candidate, in children in Bangladesh with cryptosporidiosis and diarrhea (cases) and uninfected children with diarrhea (controls), and p23 gene polymorphisms in infecting species. Serum IgM, IgG, and IgA responses to p23 were significantly greater in cases than controls after three weeks of follow-up. Cases with acute diarrhea had significantly greater serum IgA and IgM responses than those with persistent diarrhea, which suggested an association with protection from prolonged disease. The p23 sequences were relatively conserved among infecting species and subtype families. Although most children were infected with Cryptosporidium hominis, there was a cross-reactive antibody response to C. parvum antigen. These results support further development of p23 as a vaccine candidate. PMID- 22302852 TI - Evaluation of the solar water disinfection process (SODIS) against Cryptosporidium parvum using a 25-L static solar reactor fitted with a compound parabolic collector (CPC). AB - Water samples of 0, 5, and 30 nephelometric turbidity units (NTU) spiked with Cryptosporidium parvum oocysts were exposed to natural sunlight using a 25-L static solar reactor fitted with a compound parabolic collector (CPC). The global oocyst viability was calculated by the evaluation of the inclusion/exclusion of the fluorogenic vital dye propidium iodide and the spontaneous excystation. After an exposure time of 8 hours, the global oocyst viabilities were 21.8 +/- 3.1%, 31.3 +/- 12.9%, and 45.0 +/- 10.0% for turbidity levels of 0, 5, and 30 NTU, respectively, and these values were significantly lower (P < 0.05) that the initial global viability of the isolate (92.1 +/- 0.9%). The 25-L static solar reactor that was evaluated can be an alternative system to the conventional solar water disinfection process for improving the microbiological quality of drinking water on a household level, and moreover, it enables treatment of larger volumes of water (> 10 times). PMID- 22302853 TI - Mannose-binding lectin and Toll-like receptor polymorphisms and Chagas disease in Chile. AB - Mannose-binding lectin (MBL) and Toll-like receptor (TLR) polymorphisms may influence susceptibility and manifestation of Trypanosoma cruzi infection. In northern Chile, we examined 61 asymptomatic patients with chronic Chagas disease (CD), 64 patients with chronic Chagas cardiomyopathy (CCC), and 45 healthy individuals. Low-producer MBL2*B genotypes were more common in CD patients (48%) than healthy individuals (31%; adjusted odds ratio = 2.3, 95% confidence interval = 1.01-5.4, P = 0.047) but did not differ with manifestation. In contrast, the heterozygous Toll-like receptor 4 (TLR4)-deficiency genotype D299G/T399I occurred more frequently in asymptomatic (14.8%) than CCC patients (3.1%; P = 0.02). TLR1 I602S, TLR2-R753Q, TLR6-S249P, and MAL/TIRAP-S180L did not associate with CD or CCC. These findings support the complement system to be involved in defense against Trypanosoma cruzi infection and indicate that curbed TLR4 activation might be beneficial in preventing CCC. PMID- 22302854 TI - Detection and transmission of Dientamoeba fragilis from environmental and household samples. AB - Dientamoeba fragilis is a commonly occurring pathogenic protozoan often detected at higher rates in stool samples than Giardia intestinalis. However, little is known about its life cycle and mode of transmission. A total of 210 environmental and household samples were examined for the presence of D. fragilis by culture and polymerase chain reaction. Of 100 environmental samples, D. fragilis was detected only in untreated sewage. In the household samples D. fragilis was detected in 30% of household contacts tested and was not detected in any domestic pets. This study provides evidence that environmental transmission of D. fragilis is unlikely and that pets played no role in transmission of the disease in this study. Direct transmission from infected persons is the most likely mode of transmission for D. fragilis. The study also highlights the need for household contacts to be screened, given the propensity of close contacts to become infected with the organism. PMID- 22302855 TI - Verbal autopsy for neurological diseases. AB - Verbal autopsy is an interview-based technique to determine the cause distribution of death in a population. The use of verbal autopsy for understanding neurological diseases is crucial to burden of disease analyses in many countries, particularly in locations where civil registration systems are non-functioning or absent. We review the purposes, strengths, and weaknesses in the use of verbal autopsy for neurological diseases. PMID- 22302856 TI - Predictors of acute bacterial meningitis in children from a malaria-endemic area of Papua New Guinea. AB - Predictors of acute bacterial meningitis (ABM) were assessed in 554 children in Papua New Guinea 0.2-10 years of age who were hospitalized with culture-proven meningitis, probable meningitis, or non-meningitic illness investigated by lumbar puncture. Forty-seven (8.5%) had proven meningitis and 36 (6.5%) had probable meningitis. Neck stiffness, Kernig's and Brudzinski's signs and, in children < 18 months of age, a bulging fontanel had positive likelihood ratios (LRs) >= 4.3 for proven/probable ABM. Multiple seizures and deep coma were less predictive (LR = 1.5-2.1). Single seizures and malaria parasitemia had low LRs (<= 0.5). In logistic regression including clinical variables, Kernig's sign and deep coma were positively associated with ABM, and a single seizure was negatively associated (P <= 0.01). In models including microscopy, neck stiffness and deep coma were positively associated with ABM and parasitemia was negatively associated with ABM (P <= 0.04). In young children, a bulging fontanel added to the model (P < 0.001). Simple clinical features predict ABM in children in Papua New Guinea but malaria microscopy augments diagnostic precision. PMID- 22302857 TI - Infectious etiologies of acute febrile illness among patients seeking health care in south-central Cambodia. AB - The agents of human febrile illness can vary by region and country suggesting that diagnosis, treatment, and control programs need to be based on a methodical evaluation of area-specific etiologies. From December 2006 to December 2009, 9,997 individuals presenting with acute febrile illness at nine health care clinics in south-central Cambodia were enrolled in a study to elucidate the etiologies. Upon enrollment, respiratory specimens, whole blood, and serum were collected. Testing was performed for viral, bacterial, and parasitic pathogens. Etiologies were identified in 38.0% of patients. Influenza was the most frequent pathogen, followed by dengue, malaria, and bacterial pathogens isolated from blood culture. In addition, 3.5% of enrolled patients were infected with more than one pathogen. Our data provide the first systematic assessment of the etiologies of acute febrile illness in south-central Cambodia. Data from syndromic-based surveillance studies can help guide public health responses in developing nations. PMID- 22302858 TI - Saw-scaled viper bites in Sri Lanka: is it a different subspecies? Clinical evidence from an authenticated case series. AB - The saw-scaled viper (SSV) (Echis carinatus) is considered to be a highly venomous snake in Sri Lanka despite any published clinical justification. Being a rarity, the clinical profile of SSV bites is not well established in Sri Lanka. We report a series of 48 (n-48) SSV bites from the Northern Province of Sri Lanka. The majority (65%) of victims had evidence of local envenoming at the site of the bite; however, 29% showed spontaneous bleeding and 71% had coagulopathy. There were no deaths in the series. The envenoming was mild in contrast to the mortality and significant morbidity associated with SSV bites in West Africa and some parts of India. These observations need to be further explored with laboratory studies to identify the venom components, study of morphological characteristics, and genetic profiling of the Sri Lankan SSV to see if it is different from the subspecies found elsewhere. PMID- 22302859 TI - Unusual presentations of pediatric neurobrucellosis. AB - Neurobrucellosis is an uncommon complication of pediatric brucellosis. Acute meningitis and encephalitis are the most common clinical manifestations, however symptoms may be protean and diagnosis requires a high index of suspicion in patients from endemic areas. Diagnosis is often based on neurological symptoms, serology, and suggestive brain imaging because cerebrospinal fluid culture yields are low. Two cases of pediatric neurobrucellosis with unusual clinical and radiologic findings are presented. PMID- 22302860 TI - An unusual cutaneous tumor: African histoplasmosis following mudbaths: case report and review. AB - African histoplasmosis, caused by Histoplasma capsulatum var. duboisii, is endemic in Africa. The disease usually involves the skin, subcutaneous tissue, and bones. A case of African histoplasmosis presenting as a cutaneous tumor and non-healing wound in a 66-year-old immunocompetent male residing in Africa, the first ever reported following mudbaths and acupuncture, is hereby reported. Diagnosis was confirmed by means of polymerase chain reaction performed on tissue material. The patient was started on long-term itraconazole therapy and he responded well. African histoplasmosis should be included in the differential diagnosis of non-healing wounds or tumor-like lesions, especially in the context of mudbaths in an endemic area. PMID- 22302861 TI - Recurrent disseminated intravascular coagulation caused by intermittent dosing of rifampin. AB - Daily rifampin therapy is associated with minimal adverse effects, but administration on an intermittent or interrupted basis has been associated with severe immunoallergic reactions such as hemolytic anemia, acute renal failure, and disseminated intravascular coagulation. We describe a patient with Mycobacterium leprae infection who experienced recurrent episodes of disseminated intravascular coagulation after intermittent exposures to rifampin, and review eight previously reported cases of rifampin-associated disseminated intravascular coagulation. In six (75%) cases, previous exposure to rifampin was reported and seven (87.5%) patients were receiving the medication on an intermittent or interrupted basis. Clinical features of rifampin-associated disseminated intravascular coagulation included fever, hypotension, abdominal pain, and vomiting within hours of ingestion. Average time to reaction was 3-6 doses if rifampin was being administered on a monthly schedule. Three (37.5%) of eight reported cases were fatal. A complete history of previous exposure to rifampin is recommended before intermittent therapy with this medication. PMID- 22302862 TI - Pseudotumoral form of neuroschistosomiasis: report of three cases in Ganzi, China. AB - The authors report three rare cases of neuroschistosomiasis lacking extracranial involvement. No parasitic eggs were detected in the stool with the Kato-Katz thick smear methods. Computed tomography of the brains showed hypodense signals, and magnetic resonance imaging showed isointense signals on T1-weighted images, hyperintense signals on T2-weighted images, and intensely enhancing nodules in the brain after intravenous administration of gadolinium. High-grade gliomas were suspected, and operations or radiosurgery was performed. Cerebral schistosomiasis was confirmed in all cases by biopsy of the brain lesions, revealing granulomas containing embedded Schistosoma japonicum eggs. All cases were definitively diagnosed as brain schistosomiasis japonica. Praziquantel and corticosteroids were administered, and the prognoses were good for all case patients. Although the aforementioned pattern of imaging examinations is not present in all cases of neuroschistosomiasis, a diagnosis of neuroschistosomiasis should be considered when this pattern of imaging is observed; cerebrospinal fluid serological exams are also recommended. PMID- 22302863 TI - Non-invasive assessment of fibrosis using color Doppler ultrasound in patients with hepatitis C virus in the Amazon rainforest, Brazil. AB - The purpose of this study was to correlate morphologic and hemodynamic Doppler ultrasound findings as indicators of the degree of inflammation and fibrosis and to diagnose chronic vital hepatitis complications and progression. A prospective, descriptive study of a case series was conducted that analyzed Doppler ultrasound images of the liver and portal system and used the portal vein congestion index, hepatic and splenic artery impedance indices, and the liver vascular index. Of 50 patients positive for antibodies against hepatitis C virus, morphologic changes highlighted increased hepatic parenchyma echogenicity in 24%, and increased gall blander echogenicity and wall thickness in 4%. The most common hemodynamic changes observed were reduced flow velocity in the portal vein trunk in 26%, congestion index changes in 12%, liver vascular index changes in 16%, and splenic and hepatic artery impedance index changes in 14%. These indices were shown to be associated with alanine aminotransferase levels, which suggested that they are important liver damage indicators in the early phase of infection with hepatitis C virus. PMID- 22302864 TI - Prediction of child health by household density and asset-based indices in impoverished indigenous villages in rural Panama. AB - Chronic infection over a 16-month period and stunting of preschool children were compared between more spatially dense versus dispersed households in rural Panama. Chronic protozoan infection was associated with higher household density, lower household wealth index, poor household water quality, yard defecation, and the practice of not washing hands with soap before eating. Models for chronic diarrhea confirmed the importance of household wealth, water quality, sanitation, and hygiene practices. Furthermore, chronic protozoan infection was an important predictor for low height-for-age, along with low household wealth index scores, but not household density. Thus, despite better access to health related infrastructure in the more densely populated households, chronic protozoan infection was more common, and was associated with higher rates of child stunting, compared with more dispersed households. PMID- 22302865 TI - Sexually transmitted infections in newly arrived refugees: is routine screening for Neisseria gonorrheae and Chlamydia trachomatis infection indicated? AB - More than 340 million cases of bacterial and protozoal sexually transmitted infections (STIs) occur annually. Approximately 70,000 refugees arrive in the United States on a yearly basis. Refugees are a particularly disenfranchised and vulnerable population. The prevalence of Chlamydia and gonorrhea in refugee populations has not been described, and the utility of routine screening is unknown. We performed a descriptive evaluation of 25,779 refugees who completed a screening medical examination in Minnesota during 2003-2010. A total of 18,516 (72%) refugees were tested for at least one STI: 183 (1.1%) of 17,235 were seropositive for syphilis, 15 (0.6%) of 2,512 were positive for Chlamydia, 5 (0.2%) of 2,403 were positive for gonorrhea, 136 (2.0%) of 6,765 were positive for human immunodeficiency virus, and 6 (0.1%) of 5,873 were positive for multiple STIs. Overall prevalence of Chlamydia (0.6%) and gonorrhea (0.2%) infection was low, which indicated that routine screening may not be indicated. However, further research on this subject is encouraged. PMID- 22302866 TI - Factors associated with resistance to Schistosoma mansoni infection in an endemic area of Bahia, Brazil. AB - Detailed knowledge of factors associated with resistance to Schistosoma mansoni infection in endemic areas might facilitate more effective schistosomiasis control. We conducted a cross-sectional study of persons resistant to schistosomiasis and found no association between socioeconomic status and resistance to infection. Mononuclear cells of resistant subjects produced higher levels of interleukin-5 (IL-5), IL-13 and interferon-gamma upon stimulation with soluble egg antigen (SEA) compared with infected persons. When stimulated with Sm21.6 or Sm22.6, levels of IL-10 were higher in cell culture of resistant persons. Levels of IgE against soluble adult worm antigen (SWAP) and against interleukin-4-inducing principle from S. mansoni eggs (IPSE) and levels of IgG4 against SWAP, SEA, and Sm22.6 were lower in the resistant group compared with the susceptible group. Our data suggest that socioeconomic status could not fully explain resistance to S. mansoni infection observed in the studied area. However, a mixture of Th1 and Th2 immune responses and low levels of specific IgG4 against parasite antigens could be mediating resistance to infection. PMID- 22302867 TI - Comparative analysis of severe pediatric and adult leptospirosis in Sao Paulo, Brazil. AB - Although leptospirosis may be fatal in childhood, the experience of many clinicians working in disease-endemic areas is that classic Weil's disease and death are less common among pediatric patients. The aim of the study was to ascertain disease spectrum and outcome differences in severe pediatric and adult leptospirosis in a large at-risk population. Epidemiologic, clinical, and laboratory data were obtained on hospitalized cases from Sao Paulo during 2004 2006. A total of 42 case-patients < 18 years of age and 328 case-patients >= 18 years of age were tested during the study. Compared with children, adults had higher rates of jaundice (P = 0.01), elevated serum bilirubin levels (P < 0.01), oliguria (P = 0.02), and elevated creatinine levels (P = 0.01) but not for thrombocytopenia or pulmonary involvement. The overall case-fatality rate was 27% (adult) versus 5% (pediatric) (P < 0.01). Severe pediatric leptospirosis may be less likely to show all classic features of Weil's disease and may be less fatal than in adults. PMID- 22302868 TI - Leptospirosis in American Samoa 2010: epidemiology, environmental drivers, and the management of emergence. AB - Leptospirosis has recently been reported as an emerging disease worldwide, and a seroprevalence study was undertaken in American Samoa to better understand the drivers of transmission. Antibodies indicative of previous exposure to leptospirosis were found in 15.5% of 807 participants, predominantly against three serovars that were not previously known to occur in American Samoa. Questionnaires and geographic information systems data were used to assess behavioral factors and environmental determinants of disease transmission, and logistic regression was used to identify factors associated with infection. Many statistically significant factors were consistent with previous studies, but we also showed a significant association with living at lower altitudes (odds ratio [OR] = 1.53, 95% confidence interval [CI]: 1.03-2.28), and having higher numbers of piggeries around the home (OR = 2.63, 95% CI: 1.52-4.40). Our findings support a multifaceted approach to combating the emergence of leptospirosis, including modification of individual behavior, but importantly also managing the evolving environmental drivers of risk. PMID- 22302869 TI - Human risk of infection with Borrelia burgdorferi, the Lyme disease agent, in eastern United States. AB - The geographic pattern of human risk for infection with Borrelia burgdorferi sensu stricto, the tick-borne pathogen that causes Lyme disease, was mapped for the eastern United States. The map is based on standardized field sampling in 304 sites of the density of Ixodes scapularis host-seeking nymphs infected with B. burgdorferi, which is closely associated with human infection risk. Risk factors for the presence and density of infected nymphs were used to model a continuous 8 km*8 km resolution predictive surface of human risk, including confidence intervals for each pixel. Discontinuous Lyme disease risk foci were identified in the Northeast and upper Midwest, with a transitional zone including sites with uninfected I. scapularis populations. Given frequent under- and over-diagnoses of Lyme disease, this map could act as a tool to guide surveillance, control, and prevention efforts and act as a baseline for studies tracking the spread of infection. PMID- 22302870 TI - Factors associated with dengue mortality in Latin America and the Caribbean, 1995 2009: an ecological study. AB - In this study, we aimed to estimate the effect that environmental, demographic, and socioeconomic factors have on dengue mortality in Latin America and the Caribbean. To that end, we conducted an observational ecological study, analyzing data collected between 1995 and 2009. Dengue mortality rates were highest in the Caribbean (Spanish-speaking and non-Spanish-speaking). Multivariate analysis through Poisson regression revealed that the following factors were independently associated with dengue mortality: time since identification of endemicity (adjusted rate ratio [aRR] = 3.2 [for each 10 years]); annual rainfall (aRR = 1.5 [for each 10(3) L/m(2)]); population density (aRR = 2.1 and 3.2 for 20-120 inhabitants/km(2) and > 120 inhabitants/km(2), respectively); Human Development Index > 0.83 (aRR = 0.4); and circulation of the dengue 2 serotype (aRR = 1.7). These results highlight the important role that environmental, demographic, socioeconomic, and biological factors have played in increasing the severity of dengue in recent decades. PMID- 22302871 TI - Molecular detection and typing of dengue viruses from archived tissues of fatal cases by rt-PCR and sequencing: diagnostic and epidemiologic implications. AB - Diagnosis of dengue virus (DENV) infection in fatal cases is challenging because of the frequent unavailability of blood or fresh tissues. For formalin-fixed, paraffin-embedded (FFPE) tissues immunohistochemistry (IHC) can be used; however, it may not be as sensitive and serotyping is not possible. The application of reverse transcription-polymerase chain reaction (RT-PCR) for the detection of DENV in FFPE tissues has been very limited. We evaluated FFPE autopsy tissues of 122 patients with suspected DENV infection by flavivirus and DENV RT-PCR, sequencing, and DENV IHC. The DENV was detected in 61 (50%) cases by RT-PCR or IHC. The RT-PCR and sequencing detected DENV in 60 (49%) cases (DENV-1 in 16, DENV-2 in 27, DENV-3 in 8, and DENV-4 in 6 cases). No serotype could be identified in three cases. The IHC detected DENV antigens in 50 (40%) cases. The RT-PCR using FFPE tissue improves detection of DENV in fatal cases and provides sequence information useful for typing and epidemiologic studies. PMID- 22302872 TI - A three-component biomarker panel for prediction of dengue hemorrhagic fever. AB - Dengue virus infections are a major cause of morbidity in tropical countries. Early detection of dengue hemorrhagic fever (DHF) may help identify individuals that would benefit from intensive therapy. Predictive modeling was performed using 11 laboratory values of 51 individuals (38 DF and 13 DHF) obtained on initial presentation using logistic regression. We produced a robust model with an area under the curve of 0.9615 that retained IL-10 levels, platelets, and lymphocytes as the major predictive features. A classification and regression tree was developed on these features that were 86% accurate on cross-validation. The IL-10 levels and platelet counts were also identified as the most informative features associated with DHF using a Random Forest classifier. In the presence of polymerase chain reaction-proven acute dengue infections, we suggest a complete blood count and rapid measurement of IL-10 can assist in the triage of potential DHF cases for close follow-up or clinical intervention improving clinical outcome. PMID- 22302873 TI - Assessing the risk of international spread of yellow fever virus: a mathematical analysis of an urban outbreak in Asuncion, 2008. AB - Yellow fever virus (YFV), a mosquito-borne virus endemic to tropical Africa and South America, is capable of causing large urban outbreaks of human disease. With the ease of international travel, urban outbreaks could lead to the rapid spread and subsequent transmission of YFV in distant locations. We designed a stochastic metapopulation model with spatiotemporally explicit transmissibility scenarios to simulate the global spread of YFV from a single urban outbreak by infected airline travelers. In simulations of a 2008 outbreak in Asuncion, Paraguay, local outbreaks occurred in 12.8% of simulations and international spread in 2.0%. Using simple probabilistic models, we found that local incidence, travel rates, and basic transmission parameters are sufficient to assess the probability of introduction and autochthonous transmission events. These models could be used to assess the risk of YFV spread during an urban outbreak and identify locations at risk for YFV introduction and subsequent autochthonous transmission. PMID- 22302874 TI - The safety of yellow fever vaccine 17D or 17DD in children, pregnant women, HIV+ individuals, and older persons: systematic review. AB - Yellow fever vaccine provides long-lasting immunity. Rare serious adverse events after vaccination include neurologic or viscerotropic syndromes or anaphylaxis. We conducted a systematic review of adverse events associated with yellow fever vaccination in vulnerable populations. Nine electronic bibliographic databases and reference lists of included articles were searched. Electronic databases identified 2,415 abstracts for review, and 32 abstracts were included in this review. We identified nine studies of adverse events in infants and children, eight studies of adverse events in pregnant women, nine studies of adverse events in human immunodeficiency virus-positive patients, five studies of adverse events in persons 60 years and older, and one study of adverse events in individuals taking immunosuppressive medications. Two case studies of maternal-neonate transmission resulted in serious adverse events, and the five passive surveillance databases identified very small numbers of cases of yellow fever vaccine-associated viscerotropic disease, yellow fever vaccine-associated neurotropic disease, and anaphylaxis in persons >= 60 years. No other serious adverse events were identified in the other studies of vulnerable groups. PMID- 22302875 TI - Relationship of climate, geography, and geology to the incidence of Rift Valley fever in Kenya during the 2006-2007 outbreak. AB - We estimated Rift Valley fever (RVF) incidence as a function of geological, geographical, and climatological factors during the 2006-2007 RVF epidemic in Kenya. Location information was obtained for 214 of 340 (63%) confirmed and probable RVF cases that occurred during an outbreak from November 1, 2006 to February 28, 2007. Locations with subtypes of solonetz, calcisols, solonchaks, and planosols soil types were highly associated with RVF occurrence during the outbreak period. Increased rainfall and higher greenness measures before the outbreak were associated with increased risk. RVF was more likely to occur on plains, in densely bushed areas, at lower elevations, and in the Somalia acacia ecological zone. Cases occurred in three spatial temporal clusters that differed by the date of associated rainfall, soil type, and land usage. PMID- 22302877 TI - Suppression of progenitor differentiation requires the long noncoding RNA ANCR. AB - Long noncoding RNAs (lncRNAs) regulate diverse processes, yet a potential role for lncRNAs in maintaining the undifferentiated state in somatic tissue progenitor cells remains uncharacterized. We used transcriptome sequencing and tiling arrays to compare lncRNA expression in epidermal progenitor populations versus differentiating cells. We identified ANCR (anti-differentiation ncRNA) as an 855-base-pair lncRNA down-regulated during differentiation. Depleting ANCR in progenitor-containing populations, without any other stimuli, led to rapid differentiation gene induction. In epidermis, ANCR loss abolished the normal exclusion of differentiation from the progenitor-containing compartment. The ANCR lncRNA is thus required to enforce the undifferentiated cell state within epidermis. PMID- 22302876 TI - Endocrine fibroblast growth factors 15/19 and 21: from feast to famine. AB - We review the physiology and pharmacology of two atypical fibroblast growth factors (FGFs)-FGF15/19 and FGF21-that can function as hormones. Both FGF15/19 and FGF21 act on multiple tissues to coordinate carbohydrate and lipid metabolism in response to nutritional status. Whereas FGF15/19 is secreted from the small intestine in response to feeding and has insulin-like actions, FGF21 is secreted from the liver in response to extended fasting and has glucagon-like effects. FGF21 also acts in an autocrine fashion in several tissues, including adipose. The pharmacological actions of FGF15/19 and FGF21 make them attractive drug candidates for treating metabolic disease. PMID- 22302878 TI - Role of Itk signalling in the interaction between influenza A virus and T-cells. AB - Although the T-cell-mediated immune response to influenza virus has been studied extensively, little information is available on the direct interaction between influenza virus and T-cells that pertains to severe diseases in humans and animals. To address these issues, we utilized the BALB/c mouse model combined with primary T-cells infected with A/WSN/33 influenza virus to investigate whether influenza virus has an affinity for T-cells in vivo. We observed that small proportions of CD4(+) T-cells and CD8(+) T-cells in spleen and thymus expressed viral proteins in infected mice. A significant proportion of mouse primary T-cells displayed expression of alpha-2,6 sialic acid-linked influenza virus receptor and were infected directly by influenza A virus. These experiments reveal that there exists a population of T-cells that is susceptible to influenza A virus infection. Furthermore, we employed human Jurkat T-cells to investigate the virus-T-cell interaction, with particular emphasis on understanding whether Itk (interleukin-2-inducible T-cell kinase), a Tec family tyrosine kinase that regulates T-cell activation, is involved in virus infection of T-cells. Interestingly, influenza virus infection resulted in an increased recruitment of Itk to the plasma membrane and an increased level of phospholipase C-gamma1 (PLC gamma1) phosphorylation, suggesting that Itk/PLC-gamma1 signalling is activated by the virus infection. We demonstrated that depletion of Itk inhibited the replication of influenza A virus, whereas overexpression of Itk increased virus replication. These results indicate that Itk is required for efficient replication of influenza virus in infected T-cells. PMID- 22302879 TI - E2F1, ARID3A/Bright and Oct-2 factors bind to the Epstein-Barr virus C promoter, EBNA1 and oriP, participating in long-distance promoter-enhancer interactions. AB - The Epstein-Barr virus (EBV) C promoter (Cp) regulates several genes required for B-cell proliferation in latent EBV infection. The family of repeats (FR) region of the latent origin of plasmid replication (oriP) functions as an Epstein-Barr nuclear antigen 1 (EBNA1)-dependent distant enhancer of Cp activity, and the enhancer-promoter interaction is mediated by a higher-order multi-protein complex containing several copies of EBNA1. Using DNA-affinity purification with a 170 bp region of the Cp in combination with mass spectrometry, we identified the cell cycle-regulatory protein E2F1, the E2F-binding protein ARID3A, and the B-cell specific transcription factor Oct-2 as components of this multi-protein complex. Binding of the three factors to the FR region of oriP was determined by DNA affinity and immunoblot analysis. Co-immunoprecipitation and proximity ligation analysis revealed that the three factors, E2F1, ARID3A and Oct-2, interact with each other as well as with EBNA1 in the nuclei of EBV-positive cells. Using the chromatin immunoprecipitation assay, we showed that E2F1 and Oct-2 interacted with the FR part of oriP and the Cp, but the ARID3A interaction was, however, only detected at the Cp. Our findings support the hypothesis that EBNA1 initiates transcription at the Cp via interactions between multiple EBNA1 homodimers and cellular transcription factors in a large molecular machinery that forms a dynamic interaction between Cp and FR. PMID- 22302880 TI - Promotion of viral internal ribosomal entry site-mediated translation under amino acid starvation. AB - Cap-dependent and internal ribosomal entry site (IRES)-mediated translation are regulated differently within cells. Viral IRES-mediated translation often remains active when cellular cap-dependent translation is severely impaired under cellular stresses induced by virus infection. To investigate how cellular stresses influence the efficiency of viral IRES-mediated translation, we used a bicistronic luciferase reporter construct harbouring IRES elements from the following viruses: encephalomyocarditis virus (EMCV), foot-and-mouth disease virus (FMDV), hepatitis C virus (HCV) or human rhinovirus (HRV). NIH3T3 cells transfected with these bicistronic reporter constructs were subjected to different cellular stresses. Increased translation initiation was only observed under amino acid starvation when EMCV or FMDV IRES elements were present. To identify cellular mechanisms that promoted viral IRES-mediated translation, we tested the involvement of eukaryotic initiation factor 4E-binding protein (4E BP), general control non-depressed 2 (GCN2) and eukaryotic initiation factor 2B (eIF2B), as these are known to be modulated under amino acid starvation. Knockdown of 4E-BP1 impaired the promotion of EMCV and FMDV IRES-mediated translation under amino acid starvation, whereas GCN2 and eIF2B were not involved. To further investigate how 4E-BP1 regulates translation initiated by EMCV and FMDV IRES elements, we used a phosphoinositide kinase-3 inhibitor (LY294002), an mTOR inhibitor (Torin1) or leucine starvation to mimic 4E-BP1 dephosphorylation induced by amino acid starvation. 4E-BP1 dephosphorylation induced by the treatments was not sufficient to promote viral IRES-mediated translation. These results suggest that 4E-BP1 regulates EMCV and FMDV IRES mediated translation under amino acid starvation, but not via its dephosphorylation. PMID- 22302883 TI - Flumazenil-precipitated panic and dysphoria in patients dependent on benzodiazepines: a possible aid to abstinence. AB - Ten long-term users of benzodiazepines (average daily dose, 20 mg of diazepam or equivalent) who had experienced problems in withdrawing from the drugs were given an i.v. challenge with either the benzodiazepine antagonist flumazenil (1 mg injected over 30 s) or placebo (vehicle solution) in a randomized double-blind design. There were no 'pseudo withdrawal' responses to either single-blind or double-blind placebo injections, whereas flumazenil produced dramatic panic reactions in all four subjects tested, followed by characteristic benzodiazepine withdrawal symptoms. There were also small but significant rises in pulse rate and blood pressure, but no change in serum cortisol. Flumazenil-induced panic could not be entirely accounted for by a past or present diagnosis of panic disorder, and did not seem to be related to previous withdrawal problems, present benzodiazepine dosage, or to the severity of withdrawal symptoms precipitated by flumazenil in the same challenge test. Attempts to reduce benzodiazepine intake over the next 3 weeks tended to be more successful in the flumazenil group. The results are discussed with reference to possible changes in the GABA benzodiazepine system in long-term benzodiazepine users. PMID- 22302882 TI - Bovine PrP expression levels in transgenic mice influence transmission characteristics of atypical bovine spongiform encephalopathy. AB - Until recently, transmissible spongiform encephalopathy (TSE) disease in cattle was thought to be caused by a single agent strain, bovine spongiform encephalopathy (BSE) (classical BSE or BSE-C). However, due to the initiation of a large-scale surveillance programme throughout Europe, two atypical BSE strains, bovine amyloidotic spongiform encephalopathy (BASE, also named BSE-L) and BSE-H have since been discovered. These atypical BSE isolates have been previously transmitted to a range of transgenic mouse models overexpressing PrP from different species at different levels, on a variety of genetic backgrounds. To control for genetic background and expression level in the analysis of these isolates, we performed here a comprehensive comparison of the neuropathological and molecular properties of all three BSE agents (BASE, BSE-C and BSE-H) upon transmission into the same gene-targeted transgenic mouse line expressing the bovine prion protein (Bov6) and a wild-type control of the same genetic background. Significantly, upon challenge with these BSE agents, we found that BASE did not produce shorter survival times in these mice compared with BSE-C, contrary to previous studies using overexpressing bovine transgenic mice. Amyloid plaques were only present in mice challenged with atypical BSE and neuropathological features, including intensity of PrP deposition in the brain and severity of vacuolar degeneration were less pronounced in BASE compared with BSE-C-challenged mice. PMID- 22302884 TI - Commentary on 'Flumazenil-precipitated panic and dysphoria in patients dependent on benzodiazpines: a possible aid to abstinence'. PMID- 22302885 TI - Flumazenil-precipitated panic and dysphoria in patients dependent on benzodiazepines: a possible aid to abstinence--authors' response. PMID- 22302886 TI - Alprazolam withdrawal symptoms in agoraphobia with panic disorder: observations from a controlled Anglo-Canadian study. AB - The study examines the effect of discontinuing alprazolam in panic disorder+agoraphobia patients. Fifty-seven alprazolam and 50 placebo agoraphobia+panic disorder patients, who had participated in an 8 week double- blind controlled study of alprazolam at average doses of 5 mg daily, were withdrawn gradually from their medication over the subsequent 8 weeks. The effects of discontinuation of medication on anxiety, panic, depression, phobia and withdrawal symptoms were examined during the taper phase and over the following 6 months. Alprazolam patients deteriorated on anxiety, panics, Hamilton depression and phobia. There was no difference between the two drug groups on rebound. Serious withdrawal symptoms did not arise, but weight loss, sweating and muscle twitching were more common in alprazolam patients. The deterioration in alprazolam patients persisted up to 6 months post-taper. A high dose of alprazolam at week 8 was the best predictor of subsequent deterioration. Discontinuation of alprazolam leads to recurrence of the original disorder in some patients. Rebound and severe withdrawal reactions were not found during gradual taper of alprazolam, but minor withdrawal symptoms did arise. The study shows the importance of using gradual taper to minimize withdrawal effects. PMID- 22302881 TI - Efficient transmission and persistence of low-frequency SIVmac251 variants in CD8 depleted rhesus macaques with different neuropathology. AB - Infection of CD8-depleted rhesus macaques with the genetically heterogeneous simian immunodeficiency virus (SIV)mac251 viral swarm provides a rapid-disease model for simian acquired immune deficiency syndrome and SIV-encephalitis (SIVE). The objective was to evaluate how the diversity of the swarm influences the initial seeding of the infection that may potentially affect disease progression. Plasma, lymphoid and non-lymphoid (brain and lung) tissues were collected from two infected macaques euthanized at 21 days post-infection (p.i.), as well as longitudinal specimens and post-mortem tissues from four macaques followed throughout the infection. About 1300 gp120 viral sequences were obtained from the infecting SIVmac251 swarm and the macaques longitudinal and post-mortem samples. Phylogenetic and amino acid signature pattern analyses were carried out to assess frequency, transmission dynamics and persistence of specific viral clusters. Although no significant reduction in viral heterogeneity was found early in infection (21 days p.i.), transmission and replication of SIV variants was not entirely random. In particular, two distinct motifs under-represented (<4 %) in the infecting swarm were found at high frequencies (up to 14 %) in all six macaques as early as 21 days p.i. Moreover, a macrophage tropic variant not detected in the viral swarm (<0.3 %) was present at high frequency (29-100 %) in sequences derived from the brain of two macaques with meningitis or severe SIVE. This study demonstrates the highly efficient transmission and persistence in vivo of multiple low frequency SIVmac251 founder variants, characterized by specific gp120 motifs that may be linked to pathogenesis in the rapid-disease model of neuroAIDS. PMID- 22302887 TI - Caffeine withdrawal symptoms and rate of metabolism. AB - Forty normal subjects (mean age 36) had their caffeine intake estimated by keeping a diary (n=40) and also by analysing provided samples of tea and coffee (n=28). A test dose of caffeine (500 mg) was given and a series of salivary samples analysed to estimate pharmacokinetic measures of the rate of caffeine metabolism. They then underwent 48 h of placebo substitution using double-blind procedures. A wide range of physiological, psychological and subjective measures were taken on successive days during withdrawal and resumption of caffeine. On withdrawal, 27 subjects reported tiredness and 18 developed headache. Electroencephalograph, skin conductance and blood pressure changes were apparent. Sleep improved on withdrawal but subjects reported feeling less alert and more tired. The higher the usual caffeine intake, the greater the unpleasant feelings on withdrawal and the more marked the reversal of feelings on resumption. The faster the metabolism of caffeine, the less the drop in anxiety during withdrawal and the less its return on resumption. These correlations were, however, rather weak and sporadic. PMID- 22302888 TI - Regional differences in the effect of haloperidol and atypical neuroleptics on interstitial levels of DOPAC in the rat forebrain: an in vivo microdialysis study. AB - The effect of 'typical' and 'atypical' neuroleptics on interstitial levels of the dopamine metabolite 3,4- dihydroxyphenylacetic acid ([DOPAC]e) in the dorsolateral striatum (DLSt), the nucleus accumbens (NAc) and the medial prefrontal cortex (PFC) was investigated in awake rats by use of the microdialysis technique. All neuroleptics increased [DOPAC]e in the DLSt, NAc and in PFC. However, the 'atypical' neuroleptics clozapine, risperidone, sertindole and NNC 22-0031 showed an apparent cortical selectivity by preferentially elevating [DOPAC]e in the PFC compared with the DLSt and NAc, a feature which was not observed with the 'typical' neuroleptic haloperidol. Our data suggest that 'atypical' neuroleptics can be differentiated from the 'typical' neuroleptic, haloperidol, with respect to their ability to increase [DOPAC]e in PFC relative to DLSt and NAc. PMID- 22302889 TI - Some behavioural and neurochemical effects of ipsapirone in two rodent models of depression. AB - The effect of ipsapirone (3 and 10 mg/kg once daily, i.p. for 21 days), was assessed in two animal models of depression, namely the forced swim test and on the hyperactive response of the olfactory bulbectomized (OB) rat in the 'open field' test. The response to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.15 mg/ kg, s.c.)-induced hypothermia in rats was examined on day 16 of ipsapirone treatment. In the forced swim test, subacute treatment with ipsapirone (3 and 10 mg/kg) significantly reduced the immobility time in both sham and OB groups. In the OB rat model, chronic treatment with 10 mg/kg ipsapirone antagonized the lesion- induced hyperactivity in the 'open field' apparatus. The hypothermic response to 8-OH-DPAT was attenuated after chronic treatment with 3 mg/kg ipsapirone in both sham and OB groups, while 10 mg/kg ipsapirone attenuated this temperature reduction only in the sham group (p<0.05). Ipsapirone (10 mg/kg) significantly increased home cage locomotor activity counts on days 15 and 21 of drug treatment in the OB dose group, but only on day 21 in the sham dose group (p < 0.05). Ipsapirone (10 mg/kg) caused a significant reduction in rectal temperature 30 min following drug administration in the sham group on day 1 (p < 0.05) but in the OB group on days 1, 7, 15 and 22 (p < 0.05) of drug treatment. No significant differences in basal serum corticosterone concentrations were found either associated with olfactory bulbectomy or drug treatment. Chronic ipsapirone treatment did not attenuate the reductions in noradrenaline and serotonin in the frontal cortex of OB animals. It can be concluded that ipsapirone shows antidepressant-like activity in the forced swim test and the OB rat model of depression. PMID- 22302890 TI - The effects of sub-anaesthetic doses of ketamine on memory, cognitive performance and subjective experience in healthy volunteers. AB - The cognitive and subjective effects of sub-anaesthetic doses of ketamine on healthy volunteers were examined. Twelve healthy volunteers received 25 mg ketamine, 10 mg ketamine and saline placebo, i.m. in a double-blind, Latin square design. A cognitive, perceptual and self-report test battery was administered over 45 min. The order of tests was rotated to control for timing effects. Ketamine (25 mg) significantly affected verbal learning and memory, parallel visual search, some measures of psychomotor performance, measures of arousal, subjective mood ratings and visual perception. Measures of attention and frontal lobe functioning were relatively unaffected. Thus, low doses of ketamine had selective, dose-related effects on memory, perceptual and psychomotor functions. The disruption of memory and perceptual processes may help to explain the unique subjective state induced by ketamine. PMID- 22302891 TI - Sedative antidepressants impair visual detection mechanisms in humans. AB - The safety of sedative antidepressants is a topical issue in the treatment of depression, with driving impairment being of particular concern. We have recently completed a study with normal male volunteers comparing the actions of dothiepin (a traditional, sedating antidepressant) with those of fluvoxamine (one of the selective serotonin re-uptake-inhibiting SSRI class of newer antidepressants) on psychomotor functions relevant to driving. We set out to investigate whether these drugs impair visual selective attention (focused and divided) by employing the 'odd-ball' task. Subjects were required to respond to letters of the alphabet (T for target and other letters for non-targets) that were presented at the centre and/or periphery of the computer screen. The task has been shown to be useful in detecting differences between drugs in their effects on selective attention. Preliminary results show that dothiepin delayed responses to single targets compared with fluvoxamine and placebo. There was also preliminary evidence that it mainly affected response times to peripheral targets. Furthermore, there was preliminary evidence that both drugs delayed responses to central targets compared with placebo on the divided attention trials. Finally, response accuracy in detecting peripheral targets was greater under placebo compared with fluvoxamine and dothiepin. The impairment produced by dothiepin is presumably a consequence of the central blockade of cholinergic muscarinic or histaminergic H1 receptors. It could contribute to the reported association between the tricyclic class of antidepressants and road traffic accidents, and would be worth further investigation in depressed patients taking both classes of drug. PMID- 22302892 TI - The effect of chlorpromazine and benzhexol on memory and psychomotor function in healthy volunteers. AB - Both antipsychotic and anticholinergic drugs have been implicated in the production of the memory deficits seen in schizophrenia. We compared the effects of chlorpromazine (50 mg) and benzhexol (5 mg) with placebo on a battery of tests of memory, psychomotor function and mood, in 12 healthy volunteers. Benzhexol, but not chlorpromazine, impaired both word recall and word recognition. Neither drug had an effect on long-term memory Both active compounds were associated with self-rated sedation, and chlorpromazine produced impairment in saccadic eye movements. This study supports the contention that sedation is unlikely to be the mechanism by which anticholinergic drugs exert their amnestic effect. PMID- 22302893 TI - Effects of chronic desipramine on waiting behaviour for a food reward in olfactory bulbectomized rats. AB - The effects of olfactory bulbectomy (OB) on the 'waiting behaviour' of rats for a food reward in a T-maze, as well as the effect of chronic treatment with desipramine (7.5 mg/kg, i.p. x 14 days) prior to and throughout testing was assessed. In the T-maze, the time spent in locating a reward was longer in OB rats during the first phase of the food reward test. However, all groups chose the larger reward in at least 80% of trials by day 5 of test. Upon imposition of a delay in acquisition of the larger reward (phase 2), sham-operated rats chose the larger reward in correspondingly fewer trials until, by day 5, only 13% (control sham group) and 29% (desipramine-treated sham group) of trials were for the larger but delayed reward. By contrast, both OB rat groups continued to choose the larger but delayed reward throughout phase 2 in the majority of trials. The typical behavioural hyperactivity of OB rats in the 'open field' apparatus was attenuated by chronic administration of DMI. The results suggest that the OB rat has a deficit in food-motivated behaviour and appears to have reduced adaptation of this learned response when the conditions of the test are altered. Chronic desipramine treatment did not attenuate this effect. PMID- 22302894 TI - Alterations of bromocriptine-induced penile erection by chronic lithium in rats. AB - In the present study, the effects of chronic lithium pre-treatment (30 days) on penile erection (PE) induced by bromocriptine were investigated in rats. Intraperitoneal administration of the dopamine receptor agonist, bromocriptine (4 32 mg/kg) induced PE in a biphasic manner. The maximum response was obtained with 8 mg/kg of bromocriptine and the effect was decreased with increasing doses of the drug from 8 to 32 mg/kg. When animals were pre-treated with different doses of the D-1 dopamine receptor antagonist, SCH 23390, or the D-2 dopamine receptor antagonist, sulpiride, the PE response was decreased. The response induced by bromocriptine (4-32mg/kg) was reduced in animals pre-treated with chronic lithium. SCH 23390 did not produce a larger inhibitory effect on the bromocriptine response in animals pre-treated with chronic lithium, but the inhibitory effect of sulpiride was increased in this condition. It is concluded that chronic lithium treatment may alter the D-1/D-2 receptor activity and inhibit bromocriptine-induced PE. PMID- 22302895 TI - A comparative trial use of sulpiride and risperidone in Huntington's disease: a pilot study. AB - Sulpiride and risperidone treatment significantly improved the abnormal involuntary movements of two patients with Huntington's disease on both actometer and clinical assessments. However, treatment with risperidone, but not sulpiride, significantly improved the functional activities as assessed by the Functional Disability Scale. To the best of our knowledge this is the first report of the successful treatment of Huntington's disease with risperidone. PMID- 22302896 TI - Successful treatment of urinary incontinence with clozapine in a schizophrenic patient. AB - There is evidence that urinary incontinence (UI) can develop without any organic aetiology as a direct side effect of typical antipsychotic medication. Clozapine was administered to a chronic schizophrenic patient with UI who was refractory to typical antipsychotic medication. After various laboratory and functional tests, UI was demonstrated to be unrelated to any organic aetiology. UI was monitored throughout the study as frequency (wetting the bed) per day and night. The Brief Psychiatric Rating Scale (BPRS) was also rated. Clozapine (dose-dependently) reduced both the BPRS score and frequency of UI, which were refractory to trifluoperazine and sulpiride. This is the first report of a dramatic resolution of UI in a schizophrenic patient after clozapine treatment. It is suggested that preference should be given to clozapine in such cases, since various other antipsychotic medications were ineffective and in some cases worsened the existing UI. PMID- 22302897 TI - Narrative, history and accuracy. PMID- 22302898 TI - Abstracts: the psychopharmacology of nicotine and smoking. PMID- 22302899 TI - Molecular pathways: microsatellite instability in colorectal cancer: prognostic, predictive, and therapeutic implications. AB - Microsatellite instability (MSI) is the molecular fingerprint of the deficient mismatch repair (MMR) system, which characterizes ~15% of colorectal cancers. MSI develops as a result of germline mutations in MMR genes or, more commonly, from epigenetic silencing of MLH1 in sporadic tumors occurring in a background of methylation of CpG islands in gene promoter regions and in tumors that frequently show hotspot mutations in the BRAF oncogene. MSI tumors have distinct phenotypic features and have been consistently associated with a better stage-adjusted prognosis compared with microsatellite stable tumors. MSI negatively predicts response to 5-fluorouracil and may also determine responsiveness to other drugs used for treatment of colorectal cancers. Recent data have expanded the molecular heterogeneity of MSI tumors and may contribute to our understanding of differential chemosensitivity. The ability to identify deficient MMR has important implications for patient management, and it holds promise for therapeutic exploitation and for the development of novel therapeutics. PMID- 22302900 TI - Phospho-specific flow: fixating on the target. AB - Targeted therapies are all the rage in oncology research these days. The problem remains as to how to confirm that the target is actually being hit in vivo. This report describes the application of phospho-specific flow cytometry to establish in vivo target inhibition in real time. PMID- 22302901 TI - Boundaries of the psychosis phenotype. PMID- 22302902 TI - Comparing retrospective reports to real-time/real-place mobile assessments in individuals with schizophrenia and a nonclinical comparison group. AB - Retrospective reports are often used as the primary source of information for important diagnostic decisions, treatment, and clinical research. Whether such reports accurately represent individuals' past experiences in the context of a serious mental illness such as schizophrenia is unclear. In the current study, 24 individuals with schizophrenia and 26 nonclinical participants used a mobile device to complete multiple real-time/real-place assessments daily, over 7 consecutive days. At the end of the week, participants were also asked to provide a retrospective report summarizing the same period. Comparison of the data captured by the 2 methods showed that participants from both groups retrospectively overestimated the intensity of negative and positive daily experiences. In the clinical group, overestimations for affect were greater than for psychotic symptoms, which were relatively comparable to their retrospective reports. In both samples, retrospective reports were more closely associated with the week's average than the most intense or most recent ratings captured with a mobile device. Multilevel modeling revealed that much of the variability in weekly assessments was not explained by between-person differences and could not be captured by a single retrospective estimate. Based on the findings of this study, clinicians and researchers should be aware that while retrospective summary reports of the severity of certain symptoms compare relatively well with average momentary ratings, they are limited in their ability to capture variability in one's affective or psychotic experiences over time. PMID- 22302903 TI - Only as strong as the weakest link. PMID- 22302904 TI - Cancellation of elective operations on the day of intended surgery in a Hong Kong hospital: point prevalence and reasons. AB - OBJECTIVE: To determine the point prevalence of elective surgical case cancellations and the reasons. DESIGN: Cross-sectional study. SETTING: Teaching hospital, Hong Kong. PATIENTS; Operating theatre records of elective surgery cancellations from 1 January 2009 to 31 December 2009 were retrospectively reviewed. MAIN OUTCOME MEASURES. Cancellation of scheduled elective surgery on the day of surgery and the corresponding reasons. RESULTS: Of 6234 cases scheduled, 476 were cancelled, which yielded a point prevalence of 7.6%, with a 95% confidence interval of 7.0-8.3%. The highest number of cancellations occurred in patients scheduled for major general surgical procedures (n=94, 20%), major urological procedures (n=64, 13%), major orthopaedic surgery (n=38, 8%), and ultra-major cardiothoracic surgery (n=29, 6%). The most common category for cancellation was facility (73%), followed by work-up (17%), patient (10%), and surgeon (1%). No available operating room time due to overrun of the previous surgery was the most common reason for case cancellation (n=310). Compared to general surgery, the odds of no available operating time was significantly less in orthopaedics (odds ratio=0.26; 95% confidence interval, 0.17-0.39), otolaryngology (0.25; 0.13-0.46), neurosurgery (0.36; 0.16-0.70), paediatrics (0.53; 0.31-0.87), gynaecology (0.18; 0.11-0.29), ophthalmology (0.19; 0.07 0.41), and dentistry (0.10; 0.00-0.60). CONCLUSIONS. Case cancellations were mainly due to facility factors, such as no operating room time being available. The odds of having no operating room time available varied between surgical specialties. PMID- 22302905 TI - Predictors of successful outcomes after external cephalic version in singleton term breech pregnancies: a nine-year historical cohort study. AB - OBJECTIVE: To study the success rate, predictors for success, and pregnancy outcomes after external cephalic version. DESIGN: Historical cohort study. SETTING: Regional hospital, Hong Kong. PATIENTS: All women who had singleton term breech pregnancies at term and opted for external cephalic version during 2001 and 2009. Their demographic data, clinical and ultrasound findings, procedure details, complications, and delivery outcomes were analysed. MAIN OUTCOME MEASURES: Predictive factors for successful external cephalic version. RESULTS: A total of 209 external cephalic versions were performed during the 9-year period. The success rate was 63% (75% for multiparous and 53% for nulliparous women). There was no significant complication. On univariate analysis, predictors of successful external cephalic version were: multiparity, unengaged presenting part, higher amniotic fluid index (>= 10 cm), thin abdominal wall, low uterine tone, and easily palpable fetal head (subjective assessment by practitioners before external cephalic version). On multivariate analysis, only multiparity, non-engagement of the fetal buttock and thin maternal abdomen were associated with successful external cephalic version. In all, 69% of those who had successful external cephalic version succeeded in the first roll (P<0.001), and 82% of the women with successful external cephalic versions had vaginal deliveries (93% in multiparous and 69% in nulliparous women). Uptake rate of external cephalic version was studied in the latter part of the study period (2006-2009). Whilst 735 women were eligible for external cephalic version, 131 women chose to have the procedure resulting in an uptake rate of 18%. CONCLUSION: External cephalic version was effective in reducing breech presentations at term and corresponding caesarean section rates, but the uptake rate was low. Further work should address the barriers to the low acceptance of external cephalic version. The results of this study could encourage women to opt for external cephalic version. PMID- 22302906 TI - In-house human immunodeficiency virus-1 genotype resistance testing to determine highly active antiretroviral therapy resistance mutations in Hong Kong. AB - OBJECTIVE: To determine the frequency of highly active antiretroviral therapy resistance mutations in the viral pol gene of human immunodeficiency virus-1 (HIV 1) genotypes that circulate in Hong Kong, by means of an in-house HIV-1 genotyping system. DESIGN: Retrospective study. SETTING: Two HIV clinics in Hong Kong. PATIENTS: A modified in-house genotyping resistance test was used to sequence the partial pol gene in 1165 plasma samples from 965 patients. The performance of our test was cross-compared with the US Food and Drug Administration-approved ViroSeq HIV-1 genotyping system. The results of genotyping were submitted to the Stanford HIV-1 drug resistance database for analysis. RESULTS: The cost-effective in-house genotypic resistance test (US$40) demonstrated comparable performance to the US Food and Drug Administration approved ViroSeq system. The detection limit of this in-house genotypic resistance test could reach 400 copies/mL for both HIV-1 subtype B and CRF01_AE, which were the predominant genotypes in Hong Kong. Drug resistance mutations were detected only in post-treatment samples from treatment-failure patients. However, there was no significant difference in the frequency of drug resistance mutations between subtype B and CRF01_AE. CONCLUSION: Our cost-effective in-house genotypic resistance test detected no significant difference in drug resistance-related mutations frequencies between HIV-1 subtype B and CRF01_AE in Hong Kong. A drug resistance-related mutations database for different HIV-1 genotypes should be established in Hong Kong to augment guidance for HIV treatment. PMID- 22302907 TI - Uses and abuses of paediatric electroencephalography. AB - OBJECTIVE: To investigate whether requests for standard paediatric electroencephalograms accord with guideline recommendations, subsequent changes in clinical management according to reported results, and extent to which the service meets waiting time targets. DESIGN: Case series. SETTING: Regional hospital, Hong Kong. PATIENTS: All patients aged less than 18 years who underwent electroencephalography between December 2009 and February 2010. MAIN OUTCOME MEASURES: Appropriateness of the electroencephalogram request and the impact of its findings on clinical management. RESULTS: A total of 109 patients were recruited, but requests for standard electroencephalograms were considered 'inappropriate' with respect to guidelines in 44% of the patients, of which 50% were made to diagnose 'funny turns'. The standard electroencephalogram contributed to the diagnosis or management in only 28% of patients. In all of the latter, the request for an electroencephalogram had been appropriate. Nonspecialists made referrals for 86% of the patients. Inadequate information was provided in 66% of the requests. Standard electroencephalograms were performed within guideline targets, the wait being less than 4 weeks in 95% of requests. CONCLUSION: An effective electroencephalogram service was being provided, though abuses were common. These were mainly because of misconceptions regarding the role and limitations of standard electroencephalograms. Through an educative, non confrontational approach, and with time to explain guideline recommendations to clinicians, sustainable change in practice could be achieved so as to benefit patients, clinicians, and service provision. PMID- 22302908 TI - Analgesic effects of preoperative gabapentin after tongue reconstruction with the anterolateral thigh flap. AB - OBJECTIVE: To investigate gabapentin's role in head and neck cancer surgery following the demonstration of the effectiveness of gabapentin in reducing postoperative pain. DESIGN: Non-randomised open-label trial. SETTING: Prince of Wales Hospital, Hong Kong. MAIN OUTCOME MEASURES: Pain scores, analgesic usage, and the frequency of adverse effects. PATIENTS: In patients undergoing anterolateral thigh flap reconstruction after resection of tongue carcinoma, those who had an oral dose of gabapentin before surgery were compared to those who did not. RESULTS: Postoperative pain was reduced in the gabapentin group (1.2) compared to the control group (1.7) [P=0.05]. In the gabapentin group, mean morphine (patient-controlled analgesia) use (3.5 mg), sedation scores (1.0), and antiemetic usage (0 mg metoclopramide) were all significantly reduced in comparison to the controls with respective figures of 11.4 mg, 1.6, and 12.2 mg. CONCLUSION: Single preoperative doses of gabapentin led to significant reductions in postoperative pain and nausea with reduced analgesic and antiemetic usage, without additional side-effects or increases in operative complications. PMID- 22302909 TI - Serial transverse enteroplasty for short bowel syndrome: Hong Kong experience. AB - OBJECTIVE: To report our experience with the first series of serial transverse enteroplasty operations (a novel bowel-lengthening procedure for patients with short bowel syndrome). DESIGN. Case series. SETTING: A tertiary paediatric surgery referral centre in Hong Kong. PATIENTS: Four patients with short bowel syndrome aged 11 months to 14 years underwent serial transverse enteroplasty between November 2007 and June 2010. RESULTS: A total of six such serial procedures were performed; two patients had repeated operations. Median pre serial transverse enteroplasty small bowel length was 17.5 cm. The median increase in small bowel length was 90%. One patient experienced transient postoperative intestinal obstruction that resolved after conservative management. The median postoperative follow-up period was 31 months. The median enteral nutrition tolerance increased from 24% to 47%. The median weight-for-age z score increased by 0.55, and the median weight-for-height z score increased by 0.98. One patient had successfully weaned off parenteral nutrition. CONCLUSION: Serial transverse enteroplasty is a feasible and safe treatment for short bowel syndrome patients, which helps to improve enteral nutrition and promote growth. Repeated serial transverse enteroplasty can be performed in patients with ultra-short bowel lengths. Follow-up is necessary to assess the long-term outcomes. PMID- 22302910 TI - Green pit viper antivenom from Thailand and Agkistrodon halys antivenom from China compared in treating Cryptelytrops albolabris envenomation of mice. AB - OBJECTIVE: To compare the relative efficacy of the green pit viper antivenom from Thailand and Agkistrodon halys antivenom from China. DESIGN. In-vivo experimental study. SETTING: A wildlife conservation organisation, a university, a poison information centre, and a regional hospital in Hong Kong. MAIN OUTCOME MEASURES: Pre- and post-antivenom lethal dose 50 (LD50) of the Cryptelytrops albolabris venom, median effective dose (ED50) of green pit viper antivenom and Agkistrodon halys antivenom against a lethal dose of the venom. SUBJECTS. Adult mice. RESULTS: The intraperitoneal LD50 of the venom from locally caught Cryptelytrops albolabris was 0.14 microL. After post-exposure treatment with 10 microL of antivenom, it was elevated to 0.36 microL and 0.52 microL by the green pit viper antivenom and the Agkistrodon halys antivenom, respectively. The ED50 was 32.02 microL for green pit viper antivenom and 6.98 microL for Agkistrodon halys antivenom. Both green pit viper antivenom and Agkistrodon halys antivenom ameliorated the lethality of Cryptelytrops albolabris venom in mice. CONCLUSION: The overall superior neutralisation capacity of Agkistrodon halys antivenom over green pit viper antivenom may be related to the geographic proximity of the venoms used for antivenom preparation. The results point towards the need for further comparison of the two antivenoms on protein or immunoglobulin weight basis, and with respect to non-lethal clinically significant toxicities. PMID- 22302911 TI - Workshop 4--Sources of bias in case-referent studies. PMID- 22302912 TI - Reviewing evidences on the management of patients with motor neuron disease. AB - OBJECTIVE: To review evidences on the management of patients with motor neuron disease. DATA SOURCES: PubMed literature searches from January 1982 up to January 2011. STUDY SELECTION: Key words for literature search were "motor neuron disease review (MND)". Only the articles which concentrated on the ventilation, nutrition, cognitive or multidisciplinary approaches for motor neuron disease were included. Case reports were not included in the review. In addition, publications were identified using the World Wide Web from references in these papers. Only articles in English were considered. DATA EXTRACTION: A total of 782 articles were retrieved using the key word search, of which 72 concentrated on ventilation, nutrition, cognitive or multidisciplinary approaches. From these, 43 articles were eventually included and formed the basis of this review. DATA SYNTHESIS: Motor neuron disease is an adult-onset neurodegenerative disease that leads to weakness of limb, bulbar, and respiratory muscles. It displays an ethnic variation in incidence; 90% of cases are sporadic and 10% are familial. New diagnostic criteria have been proposed to increase diagnostic sensitivity. Proper clinical studies, electrophysiology, and neuroimaging are necessary before reaching a diagnosis of motor neuron disease. Riluzole remains the only disease modifying drug approved for this disease; it prolongs life by 3 to 4 months. Multidisciplinary care units are important in the management of motor neuron disease patients. Non-invasive positive pressure ventilation prolongs life in motor neuron disease patients with respiratory failure. Enteral feeding is usually recommended for affected patients with malnutrition. Cognitive impairment is common in these patients, for whom a formal neuropsychiatric assessment is recommended. Appropriate palliative care is needed for these patients in order to improve their quality of dying. CONCLUSION: Motor neuron disease is an incurable disease, for which a highly effective treatment is still pending. Symptomatic treatment remains the mainstay of management. A multidisciplinary approach embracing advances in non-invasive ventilation and gastrostomy can improve quality of life and extend the survival of motor neuron disease patients. PMID- 22302913 TI - Rehabilitation in older people: know more, gain more. AB - Functional decline is common among older patients during or even prior to hospitalisation, in spite of treatment of acute illnesses. An effective rehabilitation programme is vital to improve the motor and functional states of the older patients. Knowing factors affecting rehabilitation of older persons is important for their effective and efficient rehabilitation. This article, with special reference to local studies, examines age, gender, cognitive function, and serum albumin levels as to how they influence rehabilitation in the elderly. The conclusion is that we should not exclude patients of advanced age from rehabilitation programmes, based on poor cognitive function and low serum albumin levels as they can achieve similar gains in motor and functional outcomes. A nutritional programme to improve the albumin level of older persons could speed up the rehabilitation progress, rendering it more efficient. A gender-specific rehabilitation programme is needed to improve functional outcome in men and motor outcome in women. Moreover, knowing the factors influencing residential care home placement affords an opportunity to reduce reliance on institutionalisation after rehabilitation. PMID- 22302914 TI - Neonatal herpes: what lessons to learn. AB - Vesicular rashes in neonates are challenging in terms of diagnosis and management. Herpes infection is an important diagnostic consideration. We report two illustrative neonatal cases of herpesvirus infections with vesicular rashes. Such babies may be remarkably asymptomatic. A high index of suspicion leading to a prompt diagnosis, timely quarantine measures, and institution of antiviral treatment are pivotal for desirable outcomes. PMID- 22302915 TI - Acute ischaemic stroke during short-term travel to high altitude. AB - This is a case report of a young healthy adult who had acute cerebral infarcts after a short-term visit to high-altitude area. He developed acute onset of right sided limb weakness and right hemianopia a few hours after arrival at an altitude of 3600 m by train. He was initially treated for high-altitude cerebral oedema but later computed tomography and magnetic resonance imaging confirmed ischaemic infarcts in the medial left occipital lobe and left thalamus. Subsequent investigations, including laboratory tests and imaging including an echocardiogram, revealed no culpable predisposing factors. PMID- 22302916 TI - Giant urethral diverticulum calculus presenting as scrotal abscess. AB - We report herein a patient with a urethral calculus associated with urethral diverticulum. A 39-year-old man presented with scrotal swelling and acute retention of urine. Computed tomography of the pelvis and cystoscopy demonstrated a giant calculus in the proximal penile urethra. Emergency in-situ lithotripsy was performed. Complete stone clearance was achieved and a large urethral diverticulum was encountered. The rare occurrence of urethral diverticulum and associated stone disease were discussed. PMID- 22302917 TI - Cough mixture abuse and rhabdomyolysis. AB - Cough mixture abuse is an emerging problem among young men in Oriental countries. Its metabolic consequences have been recognised only recently. Such abusers can develop severe folate deficiency, which may be related to peripheral and central nervous system defects. We report three cough mixture abusers with rhabdomyolysis. All suffered from folate deficiencies and also had a history of anti-psychotic drug use. This represents one more life-threatening side-effect from cough mixture abuse. PMID- 22302918 TI - Osteoid osteoma of the calcaneum: a small painful lesion causing confusing symptoms. PMID- 22302919 TI - Occult posterior cruciate ligament avulsion fracture in a paediatric patient: easily missed diagnosis. PMID- 22302920 TI - Strategies to consider: telestroke and 24-hour primary stroke centres. PMID- 22302921 TI - An appeal to medical journal editors: the need for a full description of laboratory methods and specimen handling in clinical study reports. PMID- 22302922 TI - A role for fibrocytes in peritoneal fibrosis? PMID- 22302923 TI - Peritoneal dialysis patients with critical illness: insurance may be hard to come by. PMID- 22302924 TI - Intraperitoneal IL-6 signaling in incident patients treated with icodextrin and glucose bicarbonate/lactate-based peritoneal dialysis solutions. AB - OBJECTIVE: In this study, we compared the activity of interleukin-6 (IL-6), a marker of ongoing peritoneal inflammation and biocompatibility, and its other signaling components, the soluble IL-6 receptor (sIL-6R) and soluble Gp130 (sGp130), in peritoneal effluent from patients treated with icodextrin-based (E) peritoneal dialysis (PD) solution and glucose-based bicarbonate/lactate-buffered (P) solution. METHODS: Using baseline peritoneal ultrafiltration capacity, 33 stable incident PD patients were allocated either to P only (n = 20) or to P plus E for the overnight dwell (n = 13). We used ELISA to determine IL-6, sIL-6R, and sGp130 in timed overnight effluent at 1, 6, and 12 months after PD initiation. Flow cytometry was used to measure expression of IL-6R and Gp130 on isolated peritoneal leukocytes at the same time points. Peritonitis was an exclusion criterion. RESULTS: At all time points, levels of IL-6 and sIL-6R, and the appearance rates of IL-6 (90.5 pg/min vs. 481.1 pg/min, p < 0.001; 138.6 pg/min vs. 1187.5 pg/min, p < 0.001; and 56.1 pg/min vs. 1386.0 pg/min, p < 0.001), sIL 6R (2035.3 pg/min vs. 4907.0 pg/min, p < 0.01; 1375.0 pg/min vs. 6348.4 pg/min, p < 0.01; and 1881.3 pg/min vs. 5437.8 pg/min, p < 0.01), and sGp130 (37.6 ng/min vs. 65.4 ng/min, p < 0.01; 39.2 ng/min vs. 80.6 ng/min, p < 0.01; 27.8 ng/min vs. 71.0 ng/min, p < 0.01) were significantly higher in peritoneal effluent from E treated patients than from P-treated patients. Expression of IL6-R and Gp130 on individual leukocyte types isolated from PD effluent did not differ between E- and P-treated patients. The numbers of white blood cells present in effluent were higher in E-treated than in P-treated patients at all time points, but no significant differences were seen in the differential counts or in the number of exfoliated mesothelial cells. The IL-6 parameters in effluent from E-treated patients correlated with their plasma C-reactive protein. Despite the increased activation of the IL-6 system, no increase in peritoneal permeability as assessed by the dialysate-to-plasma ratio of creatinine in E effluent or by systemic inflammation was observed throughout the study. CONCLUSIONS: Higher levels of IL 6, its soluble receptors, and leukocyte expression were observed in E-treated than in P-treated patients, but this difference was not associated with alterations in peritoneal permeability or systemic inflammation during 1 year of follow-up. Leukocyte counts in effluent from E-treated patients were within the normal range previously reported for glucose solutions. This lack of clinical consequences may be a result of a parallel rise in sIL-6R and sGp130, which are known to control the biologic activity of IL-6. The utility of IL-6 level determinations, in isolation, for assessing the biocompatibility of PD solutions is questionable. PMID- 22302925 TI - Residual renal function calculated from serum cystatin C measurements and knowledge of the weekly standard Kt/V urea. PMID- 22302926 TI - Patient able to stay on peritoneal dialysis after retroperitoneal-approach radical nephrectomy. PMID- 22302927 TI - Spontaneous cure of migrated peritoneal catheter. PMID- 22302928 TI - Early reinstitution of peritoneal dialysis, without interim hemodialysis, after hand-assisted retroperitoneoscopic radical nephroureterectomy. PMID- 22302929 TI - Cloudy peritoneal fluid attributable to non-dihydropyridine calcium channel blocker. PMID- 22302930 TI - Aliskiren-induced chyloperitoneum in a patient on peritoneal dialysis. PMID- 22302931 TI - Recurrent peritonitis episodes in a continuous ambulatory peritoneal dialysis patient after gynecologic procedures. PMID- 22302932 TI - Candida glabrata renal abscesses in a peritoneal dialysis patient. PMID- 22302933 TI - Ineffective normobaric LHTL: room confinement or inappropriate training intensity? PMID- 22302936 TI - Tel1(ATM) and Rad3(ATR) phosphorylate the telomere protein Ccq1 to recruit telomerase and elongate telomeres in fission yeast. AB - In fission yeast, the DNA damage sensor kinases Tel1(ATM) and Rad3(ATR) exist at telomeres and are required for telomere maintenance, but the biological role they play at telomeres is not known. Here we show that the telomere protein Ccq1 is phosphorylated at Thr 93 (threonine residue at amino acid 93) by Tel1(ATM) and Rad3(ATR) both in vitro and in vivo. A ccq1 mutant in which alanine was substituted for Thr 93 failed to recruit telomerase to telomeres and showed gradual shortening of telomeres. These results indicate that the direct phosphorylation of Ccq1 Thr 93 by Tel1 and Rad3 is involved in the recruitment of telomerase to elongate telomeres. PMID- 22302937 TI - Structural basis of agrin-LRP4-MuSK signaling. AB - Synapses are the fundamental units of neural circuits that enable complex behaviors. The neuromuscular junction (NMJ), a synapse formed between a motoneuron and a muscle fiber, has contributed greatly to understanding of the general principles of synaptogenesis as well as of neuromuscular disorders. NMJ formation requires neural agrin, a motoneuron-derived protein, which interacts with LRP4 (low-density lipoprotein receptor-related protein 4) to activate the receptor tyrosine kinase MuSK (muscle-specific kinase). However, little is known of how signals are transduced from agrin to MuSK. Here, we present the first crystal structure of an agrin-LRP4 complex, consisting of two agrin-LRP4 heterodimers. Formation of the initial binary complex requires the z8 loop that is specifically present in neuronal, but not muscle, agrin and that promotes the synergistic formation of the tetramer through two additional interfaces. We show that the tetrameric complex is essential for neuronal agrin-induced acetylcholine receptor (AChR) clustering. Collectively, these results provide new insight into the agrin-LRP4-MuSK signaling cascade and NMJ formation and represent a novel mechanism for activation of receptor tyrosine kinases. PMID- 22302935 TI - NF-kappaB, the first quarter-century: remarkable progress and outstanding questions. AB - The ability to sense and adjust to the environment is crucial to life. For multicellular organisms, the ability to respond to external changes is essential not only for survival but also for normal development and physiology. Although signaling events can directly modify cellular function, typically signaling acts to alter transcriptional responses to generate both transient and sustained changes. Rapid, but transient, changes in gene expression are mediated by inducible transcription factors such as NF-kappaB. For the past 25 years, NF kappaB has served as a paradigm for inducible transcription factors and has provided numerous insights into how signaling events influence gene expression and physiology. Since its discovery as a regulator of expression of the kappa light chain gene in B cells, research on NF-kappaB continues to yield new insights into fundamental cellular processes. Advances in understanding the mechanisms that regulate NF-kappaB have been accompanied by progress in elucidating the biological significance of this transcription factor in various physiological processes. NF-kappaB likely plays the most prominent role in the development and function of the immune system and, not surprisingly, when dysregulated, contributes to the pathophysiology of inflammatory disease. As our appreciation of the fundamental role of inflammation in disease pathogenesis has increased, so too has the importance of NF-kappaB as a key regulatory molecule gained progressively greater significance. However, despite the tremendous progress that has been made in understanding the regulation of NF-kappaB, there is much that remains to be understood. In this review, we highlight both the progress that has been made and the fundamental questions that remain unanswered after 25 years of study. PMID- 22302938 TI - Dietary obesity-associated Hif1alpha activation in adipocytes restricts fatty acid oxidation and energy expenditure via suppression of the Sirt2-NAD+ system. AB - Dietary obesity is a major factor in the development of type 2 diabetes and is associated with intra-adipose tissue hypoxia and activation of hypoxia-inducible factor 1alpha (HIF1alpha). Here we report that, in mice, Hif1alpha activation in visceral white adipocytes is critical to maintain dietary obesity and associated pathologies, including glucose intolerance, insulin resistance, and cardiomyopathy. This function of Hif1alpha is linked to its capacity to suppress beta-oxidation, in part, through transcriptional repression of sirtuin 2 (Sirt2) NAD(+)-dependent deacetylase. Reduced Sirt2 function directly translates into diminished deacetylation of PPARgamma coactivator 1alpha (Pgc1alpha) and expression of beta-oxidation and mitochondrial genes. Importantly, visceral adipose tissue from human obese subjects is characterized by high levels of HIF1alpha and low levels of SIRT2. Thus, by negatively regulating the Sirt2 Pgc1alpha regulatory axis, Hif1alpha negates adipocyte-intrinsic pathways of fatty acid catabolism, thereby creating a metabolic state supporting the development of obesity. PMID- 22302939 TI - FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis. AB - Certain white adipose tissue (WAT) depots are readily able to convert to a "brown like" state with prolonged cold exposure or exposure to beta-adrenergic compounds. This process is characterized by the appearance of pockets of uncoupling protein 1 (UCP1)-positive, multilocular adipocytes and serves to increase the thermogenic capacity of the organism. We show here that fibroblast growth factor 21 (FGF21) plays a physiologic role in this thermogenic recruitment of WATs. In fact, mice deficient in FGF21 display an impaired ability to adapt to chronic cold exposure, with diminished browning of WAT. Adipose-derived FGF21 acts in an autocrine/paracrine manner to increase expression of UCP1 and other thermogenic genes in fat tissues. FGF21 regulates this process, at least in part, by enhancing adipose tissue PGC-1alpha protein levels independently of mRNA expression. We conclude that FGF21 acts to activate and expand the thermogenic machinery in vivo to provide a robust defense against hypothermia. PMID- 22302940 TI - A monocarboxylate transporter required for hepatocyte secretion of ketone bodies during fasting. AB - To find new genes that influence liver lipid mass, we performed a genetic screen for zebrafish mutants with hepatic steatosis, a pathological accumulation of fat. The red moon (rmn) mutant develops hepatic steatosis as maternally deposited yolk is depleted. Conversely, hepatic steatosis is suppressed in rmn mutants by adequate nutrition. Adult rmn mutants show increased liver neutral lipids and induction of hepatic lipid biosynthetic genes when fasted. Positional cloning of the rmn locus reveals a loss-of-function mutation in slc16a6a (solute carrier family 16a, member 6a), a gene that we show encodes a transporter of the major ketone body beta-hydroxybutyrate. Restoring wild-type zebrafish slc16a6a expression or introducing human SLC16A6 in rmn mutant livers rescues the mutant phenotype. Radiotracer analysis confirms that loss of Slc16a6a function causes diversion of liver-trapped ketogenic precursors into triacylglycerol. Underscoring the importance of Slc16a6a to normal fasting physiology, previously fed rmn mutants are more sensitive to death by starvation than are wild-type larvae. Our unbiased, forward genetic approach has found a heretofore unrecognized critical step in fasting energy metabolism: hepatic ketone body transport. Since beta-hydroxybutyrate is both a major fuel and a signaling molecule in fasting, the discovery of this transporter provides a new direction for modulating circulating levels of ketone bodies in metabolic diseases. PMID- 22302942 TI - A double-blind, placebo-controlled study of tacrine in patients with Alzheimer's disease using SPET. AB - BACKGROUND: the effect of single-dose and long-term cholinergic enhancement with tacrine on regional cerebral perfusion was examined in patients with Alzheimer's disease using single-photon emission tomography (SPET). METHOD: 23 patients with probable Alzheimer's disease (DSM-III-R and NINCDS-ADRDA criteria) were scanned before and after a single oral dose of tacrine at the start of the study and again after 12 weeks of randomized, double-blind treatment with tacrine or placebo, using high resolution (99m)Tc-Exametazime SPET. Patients also underwent neuropsychological testing with the CAMCOG, the Mini-Mental State Examination and the Rivermead Behavioural Memory Test before and after 12 weeks of treatment. RESULTS: occipital count ratios in all regions of interest declined by 3% over 12 weeks, indicating a progression of the disease. Acute tacrine challenge resulted in a 16% increase in the superior frontal and a 11% decrease in the anterior temporal cortex. The acute effects of tacrine were modified by 12 weeks of treatment, particularly in the medial frontal (cingulate) cortex where active treatment was associated with a reduced acute tacrine response. There were no changes in cognitive function associated with active treatment. CONCLUSION: the study demonstrates the sensitivity of cerebral perfusion measures to changes during acute and medium-term tacrine treatment. PMID- 22302941 TI - The Gal3p transducer of the GAL regulon interacts with the Gal80p repressor in its ligand-induced closed conformation. AB - A wealth of genetic information and some biochemical analysis have made the GAL regulon of the yeast Saccharomyces cerevisiae a classic model system for studying transcriptional activation in eukaryotes. Galactose induces this transcriptional switch, which is regulated by three proteins: the transcriptional activator Gal4p, bound to DNA; the repressor Gal80p; and the transducer Gal3p. We showed previously that NADP appears to act as a trigger to kick the repressor off the activator. Sustained activation involves a complex of the transducer Gal3p and Gal80p mediated by galactose and ATP. We solved the crystal structure of the complex of Gal3p-Gal80p with alpha-D-galactose and ATP to 2.1 A resolution. The interaction between the proteins occurs only when Gal3p is in a "closed" state induced by ligand binding. The structure of the complex provides a rationale for the phenotypes of several well-known Gal80p and Gal3p mutants as well as the lack of galactokinase activity of Gal3p. PMID- 22302943 TI - 5-HT3 receptor antagonism and psychoactivity. AB - The purpose of this study was to assess the acute psychoactive and physiological properties of 5-HT( 3) antagonism using ondansetron as a probe. Ondansetron is used clinically as an anti-emetic but is also under treatment consideration for a range of psychiatric disorders including drug abuse. A 15 min infusion of 40 mg ondansetron, a 1 min infusion of 25 mg of cocaine (positive control) and their respective placebos were tested intravenously in eight volunteers with histories of drug abuse in a blinded cross-over study. Ondansetron responses could not be distinguished from the placebo. Cocaine produced typical subjective and physiological effects. These findings indicate that the prototypic 5-HT( 3) receptor antagonist ondansetron does not produce acute psychoactive effects when infused at doses of up to 40 mg and has no rewarding effects with this regime. PMID- 22302944 TI - Systemic idazoxan impairs performance in a non-reversal shift test: implications for the role of the central noradrenergic systems in selective attention. AB - Two experiments examined the effect of pharmacological stimulation of the locus coeruleus in a non-reversal shift paradigm to test predictions concerning the role of the ceruleo-cortical noradrenergic system in processes of selective attention. Food-deprived rats were trained to make either visual (experiment 1) or spatial (experiment 2) discriminations in a parallel alley with both sets of cues being present at all times. Two groups of rats received treatments of either 2 mg/kg i.p. of the selective alpha(2) adrenoceptor antagonist idazoxan or saline control injections before each daily block of trials. Following attainment of criterion, the reinforcement contingencies were altered according to a non reversal shift design, so that the alternative (i.e. either spatial or visual) set of cues now predicted reward. Rats treated with idazoxan were not impaired in the acquisition of either the spatial or visual discrimination task, but they were impaired in both forms of non-reversal shift. These deficits are interpreted as resulting from narrowed attention in idazoxan-treated rats, thus supporting a selective attention hypothesis of locus coeruleus function. PMID- 22302945 TI - A novel test of visual learning in the rat: effects of 8 -OH-DPAT and WAY-100579. AB - The 5-HT(1A) agonist 8-OH-DPATand the 5-HT(3) antagonist WAY-100579 were tested in a novel computerized visual learning task. Since rats show substantial learning of new problems within each single session, drug effects on new learning could be compared within subjects. Both the reaction time (RT) and choice accuracy were measured. A dose of 0.3 mg/kg of 8-OH-DPAT lengthened the RTs while 0.1 mg/kg of 8-OH-DPAT and 0.1 mg/kg of WAY-100579 shortened the RTs. In the absence of drugs, accuracy was independent of the RT for RTs > 1.5 s. Therefore, in order to unconfound the drug effects on accuracy from motor effects, only responses with longer RTs were analysed. Both 0.3 and 0.1 mg/kg of 8-OH-DPAT and 0.1 mg/kg of WAY-100579 significantly impaired accuracy, though some learning was seen in all cases. These findings may have implications for animal models of Alzheimer's disease. PMID- 22302946 TI - Comparison of benzodiazepine (BZ) receptor agonists in two rodent activity tests. AB - The effects of four BZ receptor ligands in an operant test were compared with a rotarod test. In the operant test, rats were trained to pull a chain on a schedule that regulates the probability of delivery of food pellets to maintain a steady chain-pulling rate across a 1 h test session. For the rotarod test, mice were trained to remain on a rotarod for 2 min. Diazepam (0.1-3.0 mg/kg, i.p.), FG 8205 (0.1-3.0 mg/kg, i.p.), quazepam (3.0-60.0 mg/kg, i.p.) and zolpidem (0.3 10.0 mg/kg, i.p.) each produced dose-related impairments of performance in both the chain- pulling test and the mouse rotarod test. Furthermore, the impairment in performance induced by FG 8205 (10.0 mg/kg, p.o.) was dose-dependently reversed by the BZ receptor antagonist, flumazenil (1.0-10.0 mg/kg, i.p.), indicating that the chain-pulling deficit was mediated via BZ receptor activation. Diazepam, FG 8205 and quazepam all had comparable potencies in both the rotarod assay and the chain-pulling test. However, zolpidem suppressed the chain-pulling rates at a dose 30-fold lower than that required to induce a significant deficit in the rotarod performance. As zolpidem is a preferentially sedative compound, this pattern of results is consistent with the hypothesis that the chain-pulling test is sensitive to sedation induced by BZ receptor agonists. PMID- 22302947 TI - The NMDA antagonist dizocilpine (M K801) attenuates tolerance to nicotine in rats. AB - The N-methyl-D-aspartate antagonist dizocilpine (MK801) has been shown to attenuate neuroadaptations of the locomotor activity responses seen after chronic nicotine administration in rats. The aim of the present study was primarily to examine the effects of dizocilpine on tolerance to the aversive stimulus effect of nicotine, as measured in a conditioned taste aversion (CTA) paradigm. A second aim was to determine whether the previously reported effect of dizocilpine on tolerance to the locomotor depressant effect of nicotine could be confirmed. CTA was assessed from changes in the consumption of saccharin and salt solutions and locomotor activity was measured during 30 min sessions in photocell cages. In control rats, the administration of nicotine (0.4 mg/kg s.c.) produced strong CTA and a biphasic effect on locomotor activity (depression followed by facilitation). Daily treatment for 7 days with nicotine (0.4 mg/kg s.c.) produced tolerance to the CTA and motor effects. This tolerance was not detectable in rats that had received dizocilpine (0.3 mg/kg s.c.) 30 min before each daily injection of nicotine during the period of chronic treatment. The chronic administration of dizocilpine alone did not prevent locomotor effects and CTA when nicotine was administered subsequently. These results suggest that the NMDA receptor may be involved in adaptation to both unconditioned and conditioned behavioural responses to nicotine. PMID- 22302948 TI - Involvement of 5 -HT1D receptors in cortical extracellular 5-HT release in guinea pigs on exposure to the elevated plus maze. AB - Previous studies have shown that guinea-pigs handled daily from birth exhibit on exposure to the elevated plus maze similar behaviour to rats and increased cortical extracellular 5-HT determined by in vivo microdialysis. The present study investigates the effects of a non-selective 5-HT(1) agonist 5 carboxamidotryptamine (5-CT) and the 5-HT(1D) antagonist GR 127935 on behaviour and the release of cortical extracellular 5-HT both in a familiar environment and on exposure to the elevated plus maze. In the familiar environment of the home cage GR 127935 (0.3mg/kg i.p.) had no effect on extracellular 5-HT. The non selective agonist 5-CT (0.1 mg/kg i.p) produced a prolonged decrease (-25%) in cortical 5-HT release, an effect noT antagonized by GR 127935 (0.3mg/kg). Under aversive conditions, exposure to the elevated plus maze, the release of extracellular 5-HT increased (155% of basal release), an effect abolished by 5 CT. Pre-treatment with the selective 5.HT(1D) antagonist GR 127935 antagonized the effect of 5-CT on the aversion-induced increase in extracellular 5-HT on exposure to the elevated plus maze, but did not change the effects of 5-CT on basal 5-HT release. The results suggest that GR 127935 is an effective antagonist at the 5 -HT(1D) terminal autoreceptor in vivo under conditions of increased 5- HT function. Furthermore, the results indicate that the 5-HT( 1D) receptor in the frontal cortex is functionally active under aversive conditions. PMID- 22302949 TI - Interference effects on verbal memory function, following oral lorazepam. AB - Previous studies have consistently reported deficits in verbal memory following oral lorazepam administration. The possible role of susceptibility to interference effects as a contributory mechanism in benzodiazepine amnesia has not been examined as an independent variable. In addition, most studies of benzodiazepine amnesia have not controlled for the possible confounding effects of alcohol consumption, recently reported to affect the degree of amnesia produced by lorazepam. The present study assessed the verbal memory capabilities of 24 low social drinkers (MAST score < 3) receiving either oral lorazepam (2 mg) or placebo. Interference effects on verbal memory were assessed using the Auditory herbal Learning Test, with either the interference word list (trial B) or a counting backwards task. Lorazepam significantly reduced the recall scores for list B, compared to the first presentation of list A, suggesting lorazepam may increase susceptibility to proactive interference. There was no drug effect on retroactive interference. With regard to recall per se, lorazepam impaired verbal learning for initial acquisition trials (trials 2 and 3) but not subsequent trials, where learning was comparable to the placebo. Lorazepam did not produce significant impairment in immediate and delayed recall trials. This pattern of recall does not conform to the classic profile of benzodiazepine induced amnesia; potential explanations for this are discussed. PMID- 22302950 TI - Use of a dietary manipulation to deplete plasma tyrosine and phenylalanine in healthy subjects. AB - The aim of the present study was to lower plasma concentrations of tyrosine, the amino acid precursor of noradrenaline and to determine whether this manipulation impaired noradrenergic function as measured by the evening rise in concentrations of plasma melatonin. Eight healthy volunteers received three drinks: (i) an essential amino acid load with tyrosine, (ii) the same load without tyrosine and its precursor, phenylalanine and (iii) tap water. The tyrosine- and phenylalanine deficient drink lowered plasma tyrosine by approximately 50% over 5 h. However, this did not alter the evening plasma melatonin levels compared to the other two drinks. The results suggest that amino acid loading produces a modest decline in plasma tyrosine levels but this does not lower noradrenergic neurotransmission in the pineal gland. PMID- 22302951 TI - A multicentre, double-blind, amitriptyline-controlled study of mirtazapine in patients with major depression. AB - BACKGROUND: the efficacy and tolerability of the new antidepressant mirtazapine were evaluated in a multicentre, randomized, double-blind, amitriptyline controlled, 5 week clinical study. METHOD: 156 patients with a DSM-III diagnosis of major depressive episode and 21-item Hamilton Psychiatric Rating Scale for Depression (HPRSD) score >= 18, were randomized to treatment with either mirtazapine 20-60 mg/day or amitriptyline 75-225 mg/day. RESULTS: mirtazapine and amitriptyline were equally effective in reducing depressive symptoms, as assessed by the 17-item HPRSD and MADRS scales. Mirtazapine was better tolerated than amitriptyline, with fewer drop-outs due to adverse events and lower incidences of adverse events both at the beginning and at the end of the trial. CONCLUSION: this study shows that mirtazapine is as effective as amitriptyline in treating major depression, while at the same time better tolerated. PMID- 22302952 TI - Safety and tolerability of combined treatment with moclobemide and SSRIs: a preliminary study of 19 patients. AB - Nineteen major depressed patients, resistant to previous pharmacotherapies, were treated by the addition of moclobemide (up to 600 mg/day) to paroxetine or fluoxetine (20 mg/day) for 6 weeks in an open study to assess the adverse events and tolerability. There were 77 emergent events, insomnia, headache, nausea and dizziness being the most common. Many events were rated as severe. The high rate of adverse events suggests that there may be clinically significant interactions between moclobemide and SSRIs. However, the uncontrolled data on effectiveness is encouraging and the combination deserves further attention as a strategy for treating intractable major depression. PMID- 22302953 TI - Anxiogenic activity of quinolinic acid and kynurenine in the social interaction test in mice. AB - Quinolinic acid, a metabolite of tryptophan on the kynurenine pathway, shortened the duration of social contacts (sniffings) in C57BL/6 mice which had been previously isolated for 24 h. This effect was observed at the following time intervals after i.c.v. administration: 2-6, 22-26 and 32-36 min. Locomotion was significantly less inhibited and only during the first interval. L-Kynurenine sulphate was less active. It shortened the duration of contacts only during the 32-36 min interval after i.c.v. administration. Grooming was significantly reduced by quinolinic acid at 7-11, 12-16 and 17-21 min after administration. These effects of quinolinic acid in the social interaction test are similar to those of standard anxiogens and suggest that quinolinic acid belongs to the putative endogenous anxiogens (and not only to the endogenous convulsants). The same assumption about L-kynurenine based on data in other models of anxiety has been made previously. PMID- 22302954 TI - Effect of castration and castration with hormone replacement on the plasma prolactin responses to neuroendocrine challenge with i.v. mCPP in the male rat following a low tryptophan diet. AB - Previous studies have shown that castration increased brain 5-HT synthesis and that sex steroid hormone treatment can reverse this effect. Tryptophan (TRP) depletion has been shown to reduce brain 5-HT synthesis and to cause the post synaptic 5-HT receptors to up-regulate. We have studied the effects of castration and hormone replacement on the prolactin responses to neuroendocrine challenge with the post-synaptic 5-HT agonist, m-chlorophenylpiperazine (m-CPP) in male rats on a low TRP diet. Intact rats on a low TRP diet for 6 days showed significantly enhanced PRL reponses to mCPP as compared to intact rats on a complementary control diet. Animals castrated 20 days prior to neuroendocrine testing and on a low TRP diet demonstrated a loss of the enhanced PRL response to mCPP. The enhanced PRL response was restored by treatment with 25 mg/ kg of testosterone proprionate (TP) 24 h prior to testing. Rats treated with oestradiol benzoate (OB) from initial castration, showed significantly raised basal PRL concentrations but did not show enhanced PRL responses to mCPP in animals on either a low TRP diet or on a control diet as compared to castrated controls. It is suggested that castration increases brain 5-HT in these animals which leads to a down-regulation of post-synaptic 5-HT receptors. When the animals are then subjected to a low TRP diet for 6 days, a reduction in brain 5-HT synthesis occurs, causing a rebound up-regulation of the 5-HT receptors and therefore the end effect is a stalemate between the two initial effects resulting in the loss of the enhanced response. TP but not OB treatment in these animals restores the enhanced PRL response to mCPP by reducing brain 5 -HT synthesis and returning the post synaptic 5-HT receptors to a state of up-regulation. PMID- 22302955 TI - The effectiveness of cognitive-behavior therapy for panic disorder without concurrent medication treatment: a reply to Power and Sharp. PMID- 22302956 TI - Biomarkers for oxidative stress in acute lung injury induced in rabbits submitted to different strategies of mechanical ventilation. AB - Oxidative damage has been said to play an important role in pulmonary injury, which is associated with the development and progression of acute respiratory distress syndrome (ARDS). We aimed to identify biomarkers to determine the oxidative stress in an animal model of acute lung injury (ALI) using two different strategies of mechanical ventilation. Rabbits were ventilated using either conventional mechanical ventilation (CMV) or high-frequency oscillatory ventilation (HFOV). Lung injury was induced by tracheal saline infusion (30 ml/kg, 38 degrees C). In addition, five healthy rabbits were studied for oxidative stress. Isolated lymphocytes from peripheral blood and lung tissue samples were analyzed by alkaline single cell gel electrophoresis (comet assay) to determine DNA damage. Total antioxidant performance (TAP) assay was applied to measure overall antioxidant performance in plasma and lung tissue. HFOV rabbits had similar results to healthy animals, showing significantly higher antioxidant performance and lower DNA damage compared with CMV in lung tissue and plasma. Total antioxidant performance showed a significant positive correlation (r = 0.58; P = 0.0006) in plasma and lung tissue. In addition, comet assay presented a significant positive correlation (r = 0.66; P = 0.007) between cells recovered from target tissue and peripheral blood. Moreover, antioxidant performance was significantly and negatively correlated with DNA damage (r = -0.50; P = 0.002) in lung tissue. This study indicates that both TAP and comet assay identify increased oxidative stress in CMV rabbits compared with HFOV. Antioxidant performance analyzed by TAP and oxidative DNA damage by comet assay, both in plasma, reflects oxidative stress in the target tissue, which warrants further studies in humans. PMID- 22302957 TI - Tuning of the ocular vestibular evoked myogenic potential to bone-conducted sound stimulation. AB - Ocular vestibular evoked myogenic potentials (oVEMPs) are a recently described clinical measure of the vestibulo-ocular reflex. Studies demonstrating differences in frequency tuning between air-conducted and bone-conducted (BC) oVEMPs suggest a separate vestibular (otolith) origin for each stimulus modality. In this study, 10 healthy subjects were stimulated with BC stimuli using a hand held minishaker. Frequencies were tested in the range of 50-1,000 Hz using both a constant-force and constant-acceleration method. Subjects were stimulated at the mastoid process and the forehead. For constant-force stimulation at both sites, maximum acceleration occurred around 100 Hz, in differing axes. Both forms of stimulation had low-frequency peaks of oVEMP amplitudes (constant force: mastoid, 80-150 Hz; forehead, 50-125 Hz; constant acceleration: mastoid, 100-200 Hz; forehead, 80-150 Hz), for both sites of application, despite differences in the magnitude and direction of evoked head acceleration. For mastoid stimulation, ocular responses changed from out of phase to in phase for 400 Hz and above. Our results demonstrate that BC stimuli show tuning around 100 Hz, independent of stimulus site, that is not due to skull properties. The findings are consistent with an effect on a receptor with a resonance around 100 Hz, most likely the utricle. PMID- 22302958 TI - Transcriptome signature of resistance exercise adaptations: mixed muscle and fiber type specific profiles in young and old adults. AB - This investigation examined the effects of acute resistance exercise (RE), progressive resistance training (PRT), and age on the human skeletal muscle Transcriptome. Two cohorts of young and old adults [study A: 24 yr, 84 yr (n = 28); study B: 25 yr, 78 yr (n = 36)] were studied. Vastus lateralis biopsies were obtained pre- and 4 h post-RE in conjunction with the 1st and 36th (last) training session as part of a 12-wk PRT program in study A, whereas biopsies were obtained in the basal untrained state in study B. Additionally, the muscle fiber type specific (MHC I and MHC IIa) Transcriptome response to RE was examined in a subset of young and old women from study A. Transcriptome profiling was performed using HG U133 Plus 2.0 Arrays. The main findings were 1) there were 661 genes affected by RE during the 1st and 36th training bout that correlated with gains in muscle size and strength with PRT (termed the Transcriptome signature of resistance exercise adaptations); 2) the RE gene response was most pronounced in fast-twitch (MHC IIa) muscle fibers and provided additional insight into the skeletal muscle biology affected by RE; 3) skeletal muscle of young adults is more responsive to RE at the gene level compared with old adults and age also affected basal level skeletal muscle gene expression. These skeletal muscle Transcriptome findings provide further insight into the molecular basis of sarcopenia and the impact of resistance exercise at the mixed muscle and fiber type specific level. PMID- 22302959 TI - Contraction level-related modulation of corticomuscular coherence differs between the tibialis anterior and soleus muscles in humans. AB - The sensorimotor cortex activity measured by scalp EEG shows coherence with electromyogram (EMG) activity within the 15- to 35-Hz frequency band (beta-band) during weak to moderate intensity of isometric voluntary contraction. This coupling is known to change its frequency band to the 35- to 60-Hz band (gamma band) during strong contraction. This study aimed to examine whether such contraction level-related modulation of corticomuscular coupling differs between muscles with different muscle compositions and functions. In 11 healthy young adults, we quantified the coherence between EEG over the sensorimotor cortex and rectified EMG during tonic isometric voluntary contraction at 10-70% of maximal voluntary contraction of the tibialis anterior (TA) and soleus (SOL) muscles, respectively. In the TA, the EEG-EMG coherence shifted from the beta-band to the gamma-band with increasing contraction level. Indeed, the magnitude of beta-band EEG-EMG coherence was significantly decreased, whereas that of gamma-band coherence was significantly increased, when the contraction level was above 60% of maximal voluntary contraction. In contrast to the TA, the SOL showed no such frequency changes of EEG-EMG coherence with alterations in the contraction levels. In other words, the maximal peak of EEG-EMG coherence in the SOL existed within the beta-band, irrespective of the contraction levels. These findings suggest that the central nervous system regulates the frequency of corticomuscular coupling to exert the desired levels of muscle force and, notably, that the applicable rhythmicity of the coupling for performing strong contractions differs between muscles, depending on the physiological muscle compositions and functions of the contracting muscle. PMID- 22302960 TI - Promising new photon detection concepts for high-resolution clinical and preclinical PET. AB - The ability of PET to visualize and quantify regions of low concentration of PET tracer representing subtle cellular and molecular signatures of disease depends on relatively complex biochemical, biologic, and physiologic factors that are challenging to control, as well as on instrumentation performance parameters that are, in principle, still possible to improve on. Thus, advances to the latter can somewhat offset barriers of the former. PET system performance parameters such as spatial resolution, contrast resolution, and photon sensitivity contribute significantly to PET's ability to visualize and quantify lower concentrations of signal in the presence of background. In this report we present some technology innovations under investigation toward improving these PET system performance parameters. We focus particularly on a promising advance known as 3-dimensional position-sensitive detectors, which are detectors capable of distinguishing and measuring the position, energy, and arrival time of individual interactions of multi-interaction photon events in 3 dimensions. If successful, these new strategies enable enhancements such as the detection of fewer diseased cells in tissue or the ability to characterize lower-abundance molecular targets within cells. Translating these advanced capabilities to the clinic might allow expansion of PET's roles in disease management, perhaps to earlier stages of disease. In preclinical research, such enhancements enable more sensitive and accurate studies of disease biology in living subjects. PMID- 22302961 TI - Performance of 18F-fluoro-ethyl-tyrosine (18F-FET) PET for the differential diagnosis of primary brain tumor: a systematic review and Metaanalysis. AB - For the past decade, PET with (18)F-fluoro-ethyl-tyrosine ((18)F-FET) has been used in the evaluation of patients with primary brain tumors (PBTs), but so far series have reported only a limited number of patients. The purpose of this systematic review and metaanalysis was to assess the diagnostic performance of (18)F-FET PET in patients with suspicion of PBT. METHODS: We examined studies published in the literature using MEDLINE and EMBASE databases. Inclusion criteria were use of (18)F-FET PET for initial assessment of patients with a newly diagnosed brain lesion; patients who had no radiotherapy, surgery, or chemotherapy before (18)F-FET PET; and use of histology as a gold standard. Metaanalysis was performed on a per-patient basis. We secondarily performed receiver-operating-characteristic analysis of pooled patients to determine tumor to-background ratio (TBR) of (18)F-FET uptake and best diagnostic value. RESULTS: Thirteen studies totaling 462 patients were included. For the diagnosis of PBT, (18)F-FET PET demonstrated a pooled sensitivity of 0.82 (95% confidence interval [CI], 0.74-0.88), specificity of 0.76 (95% CI, 0.44-0.92), area under the curve of 0.84 (95% CI, 0.80-0.87), positive likelihood ratio of 3.4 (95% CI, 1.2-9.5), and negative likelihood ratio of 0.24 (95% CI, 0.14-0.39). Receiver-operating characteristic analysis indicated that a mean TBR threshold of at least 1.6 and a maximum TBR of at least 2.1 had the best diagnostic value for differentiating PBTs from nontumoral lesions. CONCLUSION: (18)F-FET PET demonstrated excellent performance for diagnosing PBTs. Strict standardization of PET acquisition protocols and prospective, multicenter studies investigating the added value over current MRI are now needed to establish (18)F-FET PET as a highly relevant tool for patient management. PMID- 22302962 TI - Dosimetry based on 99mTc-macroaggregated albumin SPECT/CT accurately predicts tumor response and survival in hepatocellular carcinoma patients treated with 90Y loaded glass microspheres: preliminary results. AB - Radioembolization of liver cancers using (90)Y-loaded microspheres is experiencing more widespread use. However, few data are available concerning the doses delivered to the tumors and the healthy liver. This retrospective study was conducted to calculate the tumor dosimetry (planned tumor dose [T(plan) D]) and nontumor dosimetry in patients treated by (90)Y-loaded glass microspheres and determine whether tumor dosimetry could predict response and survival. METHODS: Thirty-six patients with hepatocellular carcinoma (HCC), including 16 with portal vein thrombosis (PVT), were treated with (90)Y-loaded glass microspheres. The T(plan) D and the dose delivered to the injected healthy liver were calculated using a quantitative analysis of the (99m)Tc-macroaggregated albumin ((99m)Tc MAA) SPECT/CT exam. Responses were assessed after 3 mo, using the criteria of the European Association for the Study of the Liver. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier tests. RESULTS: The response rate was 69% for the overall population and 75% for the PVT patients. The dose delivered to the tumor was the only parameter associated with response with multivariate analysis (P = 0.019). A threshold T(plan) D value of 205 Gy was predictive of response, with a sensitivity of 100% and an accuracy of 91%. Quantitative (99m)Tc-MAA SPECT/CT allowed us to increase the injected activity for 4 patients with large lesions. PFS was only 5.2 mo and OS 9 mo when using a T(plan) D of less than 205 Gy versus 14 mo (P = 0.0003) and 18 mo (P = 0.0322), respectively, with a T(plan) D of 205 Gy or more. CONCLUSION: Quantitative (99m)Tc-MAA SPECT/CT is predictive of response, PFS, and OS. Dosimetry based on (99m)Tc-MAA SPECT/CT can be used for the selection of patients and for an adaptation of treatment planning, especially in selected patients (particularly in the case of large tumors). These results also confirm the efficacy and safety of (90)Y-loaded microspheres in treating HCC, even in the presence of PVT (and especially when (99m)Tc-MAA uptake is seen inside the PVT). PMID- 22302963 TI - Modern nuclear imaging for paragangliomas: beyond SPECT. AB - Paragangliomas are rare neuroendocrine tumors that may arise anywhere along the paraganglial system, with a high frequency of hereditary forms or multifocal disease. Most often, paragangliomas are benign and progress slowly, but metastases may occur in about 10% of patients. In this respect, nuclear imaging in combination with anatomic imaging may be required to fully delineate the extent of the disease. PET has been increasingly used in imaging paraganglioma, paralleled by great efforts toward the development of new tracers. Recent data indicate that the choice of PET tracers should be tailored to tumor localization and to the patient's genetic status. This article provides insight into the many PET radiotracers that are currently available and others that are still only under research and guides clinicians toward appropriate use in relation to genetic carrier status. In addition, this article provides nuclear medicine physicians with the background knowledge required for understanding relationships between imaging phenotypes and molecular genetics. PMID- 22302964 TI - Stratification of nucleoside analog chemotherapy using 1-(2'-deoxy-2'-18F-fluoro beta-D-arabinofuranosyl)cytosine and 1-(2'-deoxy-2'-18F-fluoro-beta-L arabinofuranosyl)-5-methylcytosine PET. AB - The ability to measure tumor determinants of response to nucleoside analog (NA) chemotherapy agents such as gemcitabine and related compounds could significantly affect the management of several types of cancer. Previously we showed that the accumulation in tumors of the new PET tracer 1-(2'-deoxy-2'-(18)F-fluoro-beta-d arabinofuranosyl)cytosine ((18)F-FAC) is predictive of responses to gemcitabine. (18)F-FAC retention in cells requires deoxycytidine kinase (dCK), a rate-limiting enzyme in the deoxyribonucleoside salvage metabolism and in gemcitabine conversion from an inactive prodrug to a cytotoxic compound. The objectives of the current study were to determine whether (18)F-FAC tumor uptake is also influenced by cytidine deaminase (CDA), a determinant of resistance to gemcitabine; to develop a new PET assay using (18)F-FAC and the related probe 1 (2'-deoxy-2'-(18)F-fluoro-beta-l-arabinofuranosyl)-5-methylcytosine (l-(18)F FMAC) to profile tumor lesions for both dCK and CDA enzymatic activities; and to determine whether this PET assay can identify the most effective NA chemotherapy against tumors with differential expression of dCK and CDA. METHODS: Isogenic murine leukemic cell lines with defined dCK and CDA activities were generated by retroviral transduction. A cell viability assay was used to determine the sensitivity of the isogenic cell lines to the dCK-dependent NA prodrugs gemcitabine and clofarabine. In vitro enzymatic and cell-based tracer uptake assays and in vivo PET with (18)F-FAC and l-(18)F-FMAC were used to predict tumor responses to gemcitabine and clofarabine. RESULTS: dCK and CDA activities measured by kinase and tracer uptake assays correlated with the sensitivity of isogenic cell lines to gemcitabine and clofarabine. Coexpression of CDA decreased the sensitivity of dCK-positive cells to gemcitabine treatment in vitro by 15 fold but did not affect responses to clofarabine. Coexpression of CDA decreased (18)F-FAC but not l-(18)F-FMAC, phosphorylation, and uptake by dCK-positive cells. (18)F-FAC and l-(18)F-FMAC PET estimates of the enzymatic activities of dCK and CDA in tumor implants in mice were predictive of responses to gemcitabine and clofarabine treatment in vivo. CONCLUSION: These findings support the utility of PET-based phenotyping of tumor nucleoside metabolism for guiding the selection of NA prodrugs. PMID- 22302965 TI - Molecular imaging of early alphavbeta3 integrin expression predicts long-term left-ventricle remodeling after myocardial infarction in rats. AB - (18)F-galacto-RGD ((18)F-RGD) is a PET tracer binding to alpha(v)beta(3) integrin receptors that are upregulated after myocardial infarction (MI) as part of the healing process. We studied whether myocardial (18)F-RGD uptake early after MI is associated with long-term left-ventricle (LV) remodeling in a rat model. METHODS: Wistar rats underwent sham operation (n = 9) or permanent coronary ligation (n = 25). One week after MI, rats were injected with (18)F-RGD to evaluate alpha(v)beta(3) integrin expression using a preclinical PET system. In the same rats, LV volumes and defect size were measured 1 and 12 wk after MI by (13)N ammonia PET and MRI, respectively. RESULTS: One week after MI, (18)F-RGD uptake was increased in the defect area as compared with the remote myocardium of MI rats or sham-operated controls (percentage injected dose per cubic centimeter, 0.20 +/- 0.05 vs. 0.06 +/- 0.03 and 0.07 +/- 0.04, P < 0.001). At this time, (18)F-RGD uptake was associated with capillary density in histologic sections. Average (18)F-RGD uptake in the defect area was lowest in the rats demonstrating greater than 20% relative increase in the LV end-diastolic volume from 1 to 12 wk (percentage injected dose per centimeter cubed, 0.15 +/- 0.07 vs. 0.21 +/- 0.05, P < 0.05). In a multivariable logistic regression analysis, low (18)F-RGD uptake was a significant predictor of increase in end-diastolic volume (r = 0.51, P < 0.05). CONCLUSION: High levels of (18)F-RGD uptake in the perfusion defect area early after MI were associated with the absence of significant LV remodeling after 12 wk of follow-up. These results suggest that alpha(v)beta(3) integrin expression is a potential biomarker of myocardial repair processes after MI and enables the monitoring of these processes by molecular imaging to derive possible prognostic information. PMID- 22302966 TI - From the newsline editor. PMID- 22302967 TI - MedPAC: imaging spending down. PMID- 22302968 TI - What is an NMAA? PMID- 22302969 TI - SNM submits imaging endpoint comments to FDA. PMID- 22302970 TI - Strengthening our profession through community and collaboration. PMID- 22302971 TI - Epinephrine and fear of bodily sensations in panic disorder and social phobia. AB - Fear of bodily symptoms of arousal has been implicated in the pathogenesis of both spontaneously occurring and experimentally provoked panic. Fear of bodily symptoms may be characteristic for panic disorder (PD) and is hypothesized to predict state anxiety and panic frequency during experimentally induced peripheral arousal. Twenty-eight subjects, 14 with PD and 14 with social phobia (SP) were infused with placebo and epinephrine (20, 40 and 80 ng/kg bodyweight/min) according to a fixed schedule in a single blind design. Fear of bodily symptoms was higher in subjects with PD, who also reported more bodily symptoms and higher state anxiety scores during the experiment. The panic rate (five out of 14), however, was the same in both groups. Panickers did not differ from non-panickers in trait- or baseline measures except for fear of bodily symptoms, which was marginally higher in panickers. Panickers showed greater reactivity in heart rate, diastolic blood pressure and capillary PCO(2). Our data do not support the hypothesis of a major role for fear of bodily symptoms in epinephrine-induced panic. Also, our results do not demonstrate a different reaction to epinephrine in PD and SP with situational panic attacks. PMID- 22302972 TI - Inhibition of basal and stress-induced dopamine release in the cerebral cortex and nucleus accumbens of freely moving rats by the neurosteroid allopregnanolone. AB - The neurosteroid allopregnanolone is a potent and efficacious modulator of gamma aminobutyric acid (GABA) type A receptors. The effects of intracerebroventricular injection of allopregnanolone (5 to 15 MUg in 5 MUl) on basal and stress-induced changes in the extracellular concentrations of dopamine were investigated by microdialysis in various brain areas of freely moving rats and compared with those of the benzodiazepine midazolam (1 to 10 MUg in 5 MUl). Allopregnanolone reduced (by a maximum of 65 to 75%) basal dopamine content in the prefrontal cortex and nucleus accumbens in a dose-dependent manner, but had no effect on dopamine output in the striatum. Allopregnanolone (10 to 15 MUg) also completely prevented the increase in extracellular dopamine concentrations in the nucleus accumbens and cerebral cortex induced by foot-shock stress. Midazolam reduced basal dopamine content in all three brain regions studied as well as the stress- induced increase in dopamine content in the nucleus accumbens and cerebral cortex with a greater potency than allopregnanolone. These results suggest that endogenous neurosteroids may participate in the GABAergic modulation of dopaminergic transmission in the rat cerebral cortex and nucleus accumbens, two brain areas which are important in the regulation of emotional processes. These agents do not appear to affect striatal dopaminergic transmission which modulates motor function. PMID- 22302973 TI - Discriminative stimulus produced by the imidazoline I2 site ligand, 2 -BFI. AB - 2-(2-Benzofuranyl)-2-imidazoline, RX801077 (2-BFI) which has high affinity for imidazoline I(2) binding sites and very low aflinity for alpha(2)-adrenoceptors, has been investigated for its ability to produce a discriminative stimulus (cue) in drug-discrimination studies in rats since the existence of such a cue could assist in determining the functionality of I(2) sites. All rats subjected to training proved able to discriminate the training dose of 2-BFI (33 MUmol/kg i.p) from saline vehicle and lower (5-14 MUmol/kg) doses exhibited dose-dependent substitution. The mixed alpha(2)-adrenoceptor/I( 2) site ligand idazoxan fully substituted at 40MUmol/kg. However, ethoxy idazoxan (11 MUmol/kg) and fluparoxan (13 MUmol/kg), selective alpha( 2)-adrenoceptor antagonists, also fully substituted for 2- BFI as did the monoamine oxidase (MAO) inhibitors moclobemide (99 MUmol/kg) and pargyline (153 MUmol/kg). A lower dose of moclobemide (16 MUmol/kg) exhibited partial substitution. The alpha( 2)-adrenoceptor agonists clonidine (0.1 MUmol/kg) and guanabenz (1.4 MUmol/kg), and the benzodiazepine diazepam (14 MUmol/kg), failed to substitute for 2-BFI indicating cue specificity. However, 2-BFI (14-50 MUmol/kg) substituted partially but dose dependently for clonidine (0.1 MUmol/kg) in rats trained to distinguish the latter from saline. Changes in rates of response were independent of the degree of substitution. The observed pattern of drug substitution is consistent with the previously reported ability of 2-BFI to decrease MAO activity and thus increase extracellular monoamines. PMID- 22302974 TI - The inhibition of the pupillary light reflex by the threat of an electric shock: a potential laboratory model of human anxiety. AB - It has been shown that the eye-blink response evoked by an abrupt loud white noise ('acoustic startle') is potentiated when the subjects anticipate an aversive stimulus, e.g. an electric shock ('fear-potentiated startle'). It has been proposed that this paradigm may be a useful laboratory model of human anxiety. We examined whether the threat of an electric shock, as used in the fear potentiated startle paradigm, would affect the pupillary light reflex, in 12 healthy volunteers. Light stimuli (0.32 mW/cm(2), 200 msec) were generated by a light-emitting diode, and pupil diameter was monitored by computerized binocular infrared television pupillometry in the dark. The light reflex was recorded during either the anticipation of a shock ('threat' blocks) or periods in which no shocks were anticipated ('safe' blocks). The shock consisted of a single square wave current pulse (1.5 mA, 50 msec) applied to the median nerve. At the end of each 'threat' or 'safe' block, subjects rated their anxiety using visual analogue scales. Two-factor analysis of variance (condition x block) showed that in the 'threat' condition there was a consistent increase in initial pupil diameter, a decrease in light reflex amplitude and an increase in alertness and anxiety ratings. These effects were observable before the subjects received any shock (a single stimulation of the median nerve). These results show that the anticipation of an electric shock can modify not only the startle reflex response but also the pupillary light reflex, suggesting that the inhibition of the light reflex by threat may be another suitable laboratory model of human anxiety. PMID- 22302975 TI - A study of the pharmacodynamic interaction between befloxatone and ethanol on performance and mood in healthy volunteers. AB - The effects of befloxatone (20 mg o.d. for 10 days) alone and in combination with ethanol on psychomotor performance, memory and mood were assessed in a randomized, double-blind, placebo controlled study. On treatment days 6, 8 and 10, subjects received 0.5 and 0.8 g/kg ethanol and ethanol placebo in randomly assigned, balanced orders, 2 h post-drug. Critical fusion frequency, choice reaction time, postural instability, critical tracking and mood were measured 1h before ethanol and 1, 3 and 5 h afterwards. Divided attention, sustained attention and memory (immediate and delayed recall) were also measured in single tests, 2.5-5 h post-ethanol.Ethanol's effects were generally significant when blood alcohol concentrations (BAC) after both doses were the highest; i.e. 0.48 0.67 and 0.96-1.10 mg/ml. Those effects were virtually gone after the subjects' mean BACs fell below 0.40 mg/ml. Befloxatone alone had no significant impairing effect in any test. Neither did it significantly interact with ethanol to cause any greater impairment than the latter alone. It was concluded that befloxatone does not potentiate the sedating and impairing effects of ethanol. PMID- 22302976 TI - Plasma lipid peroxide and serum vitamin E levels in subjects taking antipsychotic drugs. AB - Fourteen non-schizophrenic subjects were identified in a group general practice as taking antipsychotic medication. They were matched with a control group on age, gender and smoking status. Blood samples were taken to measure plasma lipid peroxide, serum vitamin E and cholesterol and vitamin E:cholesterol ratios. The majority of subjects were taking thioridazine (mean daily dose 42 mg, range 20 100 mg). There were no statistically significant differences between subjects and controls in any of the laboratory measures. The results in this small study therefore do not support the hypothesis that a possible source of increased free radical activity in schizophrenic patients is antipsychotic medication. PMID- 22302977 TI - Changes in head twitch response induced by a 5-hydroxytryptamine agonist in mice fed a low-protein diet. AB - Long-term intake of a protein diet in infants causes the malnutrition syndrome known as kwashiorkor. Neurological symptoms in kwashiorkor have been reported occasionally. We studied the effects of malnutrition on murine behaviour by feeding growing mice a long-term low-protein diet. Three groups of 3-week-old male ddY mice were fed protein-controlled diets of 8,15 and 25% (control group) of total diet weight for 11 weeks immediately after weaning. The number of head twitches in 2 min were measured 2 min after injection of 10 mg/kg 5 -methoxy- N,N dimethyltryptamine (5-MeODMT), a 5 -hydroxytryptamine (5 -HT) receptor agonist i.p. Organs were weighed after 10 weeks of feeding. Intracerebral monoamines and their metabolites were assayed using high performance liquid chromatography with electrochemical detection. Bodyweights of mice that were fed the 8% protein diet for 10 weeks were lower than in the other groups. The frequencies of the 5 MeODMT-induced head twitch in mice that were fed the 8% low-protein diet for 4, 7 and 10 weeks were, respectively, 37.4, 21.4 and 45.2% those of the control group. The frequencies of head twitch also decreased in mice that were fed the 15% low protein diet for 7 or 10 weeks. The locomotor activity of the mice was unchanged by the amount of protein in the diet. In assays of intracerebral monoamines, 5-HT and 5-HIAA in the whole brain and metabolic turnover of 5-HT increased significantly in mice that were fed the 8% low-protein diet for 11 weeks. Results suggest that head twitches in mice on long-term low-protein diets are suppressed due to the changes in the intracerebral serotonin system. PMID- 22302978 TI - The effect of psychotropic medication on seizure duration during bilateral electroconvulsive therapy: a retrospective study. AB - A five-year retrospective study investigating the effects of psychotropic medication on first seizure length was undertaken on 109 patients who received 131 courses of electroconvulsive therapy (ECT). Bilateral ECT was administered under methohexitone anaesthesia. Induction of a seizure was successful in 105 patients. Stepwise linear regression analysis showed that except for selective serotonin reuptake inhibitors (SSRIs) seizure length was not affected by psychotropic medication, SSRIs were associated with prolonged seizure length (p=0.0012). Less than one-third of the subjects had drugs with anticonvulsant properties omitted before treatment. Drugs with anticonvulsant properties did not shorten seizure length. Though this study suggests that SSRIs may prolong fit length, further clarification of the predictors for seizure duration is required. PMID- 22302979 TI - Benzodiazepine receptor agonists and inverse agonists yield concordant rather than opposing effects on startle responses. AB - Benzodiazepine receptor agonists and inverse agonists exert generally opposite actions at both the cellular and behavioural levels. The present study, however, reveals that both the benzodiazepine receptor agonist, chlordiazepoxide and the partial inverse agonist, FG7142, yield a dose-dependent (2-16 mg/kg, i.p) reduction in the amplitude of the acoustic startle response in the rat. The similarity in drug effects on startle was not attributable to congruent effects on basal somatic activity, as chlordiazepoxide resulted in a dose-dependent decrease in activity whereas FG7142 was associated with a small but non significant increase in activity. As these results contrast with the bidirectional actions of benzodiazepine receptor agonists and inverse agonists in behavioural tests of fear or anxiety, the neuronal mechanisms mediating the effects of benzodiazepine receptor ligands on the acoustic startle response may be distinct from those that underlie the specific fear- attenuating and potentiating actions, respectively, of benzodiazepine receptor agonists and inverse agonists. PMID- 22302980 TI - Dizziness predicts initial worsening in panic disorder: an otoneurological investigation. AB - Dizziness is a frequent complaint during the initial worsening of panic patients treated with clomipramine. In order to investigate the relationship between dizziness and initial worsening mechanisms, otoneurological tests were administered to 32 consecutive patients with panic disorder, with or without agoraphobia, before treatment, 36 h after the first dose of 25 mg clomipramine and after treatment and full remission of the panic and agoraphobic symptoms. A pretreatment complaint of 'dizziness during panic attacks' but not the occurrence of otoneurological abnormalities, predicted the occurrence of clinical worsening at the start of treatment. A specific pattern of otoneurological abnormalities was not found, but only three patients had normal results in all three sessions. The inconsistent test results suggest that functional vestibular pathology is frequently associated with panic disorder. PMID- 22302981 TI - Risperidone in the treatment of Tourette syndrome: a retrospective case note study. AB - Nineteen patients with Tourette syndrome (TS) were treated with risperidone, at a mean daily dose of 1.5 mg. Of those, 41% responded positively, 35% felt that it had made no difference, while it made 24% worse. Although 53% of the patients experienced side-effects, none had extrapyramidal side-effects. At follow-up, 8 to 11 months later, only two of 19 (11 %) patients were still taking risperidone. We suggest that risperidone does have a role in a minority of TS sufferers but it is not suggested as the first line treatment. More placebo-controlled studies using risperidone are clearly indicated. PMID- 22302982 TI - Enhanced GABAb receptor-mediated transmission in alcohol-dependence syndrome. AB - We have studied the GABAb receptor-mediated neurotransmissions of alcoholic patients by administering baclofen 10 mg orally and measuring the growth hormone (GH) response. There was a minimal GH response to the baclofen in one of eight control subjects and a greater GH response in 11 of the 16 alcoholic patients. There is thus evidence for increased transmission at the GABAb receptor in detoxified patients with alcohol-dependence syndrome. PMID- 22302983 TI - Acute psychosis following intravenous abuse of pseudoephedrine: a case report. AB - A case is reported of acute psychosis, including florid visual and tactile hallucinations, in an 18-year-old male after intravenous misuse of 60 mg of pseudoephedrine hydrochloride. The literature is reviewed for other cases of psychosis following pseudoephedrine use. PMID- 22302984 TI - Autophagy plays an essential role in the clearance of Pseudomonas aeruginosa by alveolar macrophages. AB - Intracellular bacteria have been shown to cause autophagy, which impacts infectious outcomes, whereas extracellular bacteria have not been reported to activate autophagy. Here, we demonstrate that Pseudomonas aeruginosa, a Gram negative extracellular bacterium, activates autophagy with considerably increased LC3 punctation in both an alveolar macrophage cell line (MH-S) and primary alveolar macrophages. Using the LC3 Gly120 mutant, we successfully demonstrated a hallmark of autophagy, conjugation of LC3 to phosphatidylethanolamine (PE). The accumulation of typical autophagosomes with double membranes was identified morphologically by transmission electron microscopy (TEM). Furthermore, the increase of PE-conjugated LC3 was indeed induced by infection rather than inhibition of lysosome degradation. P. aeruginosa induced autophagy through the classical beclin-1-Atg7-Atg5 pathway as determined by specific siRNA analysis. Rapamycin and IFN-gamma (autophagy inducers) augmented bacterial clearance, whereas beclin-1 and Atg5 knockdown reduced intracellular bacteria. Thus, P. aeruginosa-induced autophagy represents a host protective mechanism, providing new insight into the pathogenesis of this infection. PMID- 22302985 TI - Neuropilin-2 regulates alpha6beta1 integrin in the formation of focal adhesions and signaling. AB - The neuropilins (NRPs) contribute to the function of cancer cells in their capacity as VEGF receptors. Given that NRP2 is induced in breast cancer and correlates with aggressive disease, we examined the role of NRP2 in regulating the interaction of breast cancer cells with the ECM. Using epithelial cells from breast tumors, we defined NRP2(high) and NRP2(low) populations that differed in integrin expression and adhesion to laminin. Specifically, the NRP2(high) population adhered more avidly to laminin and expressed high levels of the alpha6beta1 integrin than the NRP2(low) population. The NRP2(high) population formed numerous focal adhesions on laminin that were not seen in the NRP2(low) population. These results were substantiated using breast carcinoma cell lines that express NRP2 and alpha6beta1 integrin. Depletion experiments revealed that adhesive strength on laminin but not collagen is dependent on NRP2, and that VEGF is needed for adhesion on laminin. A specific interaction between NRP2 and alpha6beta1 integrin was detected by co-immunoprecipitation. NRP2 is necessary for focal adhesion formation on laminin and for the association of alpha6beta1 integrin with the cytoskeleton. NRP2 also facilitates alpha6beta1-integrin mediated activation of FAK and Src. Unexpectedly, we discovered that NRP2 is located in focal adhesions on laminin. The mechanism by which NRP2 regulates the interaction of alpha6beta1 integrin with laminin to form focal adhesions involves PKC activation. Together, our data reveal a new VEGF-NRP2 signaling pathway that activates the alpha6beta1 integrin and enables it to form focal adhesions and signal. This pathway is important in the pathogenesis of breast cancer. PMID- 22302986 TI - Tiam1-regulated osteopontin in senescent fibroblasts contributes to the migration and invasion of associated epithelial cells. AB - The tumor microenvironment undergoes changes concurrent with neoplastic progression. Cancer incidence increases with aging and is associated with tissue accumulation of senescent cells. Senescent fibroblasts are thought to contribute to tumor development in aging tissues. We have shown that fibroblasts deficient in the Rac exchange factor Tiam1 promote invasion and metastasis of associated epithelial tumor cells. Here, we use a three-dimensional culture model of cellular invasiveness to outline several steps underlying this effect. We find that stress-induced senescence induces decreased fibroblast Tiam1 protein levels and increased osteopontin levels, and that senescent fibroblast lysates induce Tiam1 protein degradation in a calcium- and calpain-dependent fashion. Changes in fibroblast Tiam1 protein levels induce converse changes in osteopontin mRNA and protein. Senescent fibroblasts induce increased invasion and migration in co cultured mammary epithelial cells. These effects in epithelial cells are ameliorated by either increasing fibroblast Tiam1 or decreasing fibroblast osteopontin. Finally, in seeded cell migration assays we find that either senescent or Tiam1-deficient fibroblasts induce increased epithelial cell migration that is dependent on fibroblast secretion of osteopontin. These findings indicate that one mechanism by which senescent fibroblasts promote neoplastic progression in associated tumors is through degradation of fibroblast Tiam1 protein and the consequent increase in secretion of osteopontin by fibroblasts. PMID- 22302987 TI - Presenilin-2 regulates the degradation of RBP-Jk protein through p38 mitogen activated protein kinase. AB - Transcriptional regulation performs a central role in Notch1 signaling by recombining binding protein Suppressor of Hairless (RBP-Jk)--a signaling pathway that is widely involved in determination of cell fate. Our earlier work demonstrated the possible regulation of the Notch1-RBP-Jk pathway through protein degradation of RBP-Jk; however, the potential regulator for the degradation of RBP-Jk remains to be determined. Here, we report that the expression of endogenous and exogenous RBP-Jk was increased significantly in cells treated with proteasome- and lysosome-specific inhibitors. The effects of these inhibitors on RBP-Jk occurred in a dose- and time-dependent manner. The level of RBP-Jk protein was higher in presenilin-2 (PS2)-knockout cells than in presenilin-1 (PS1) knockout cells. Furthermore, the level of RBP-Jk was decreased by expression of PS2 in PS1 and PS2 double-knockout cells. We also found that PS1-knockout cells treated with a specific inhibitor of p38 mitogen-activated protein kinase ? (MAPK) had significantly increased levels of RBP-Jk. p38 MAPK phosphorylates RBP Jk at Thr339 by physical binding, which subsequently induces the degradation and ubiquitylation of the RBP-Jk protein. Collectively, our results indicate that PS2 modulates the degradation of RBP-Jk through phosphorylation by p38 MAPK. PMID- 22302988 TI - CFTR regulation in human airway epithelial cells requires integrity of the actin cytoskeleton and compartmentalized cAMP and PKA activity. AB - The cystic fibrosis transmembrane conductance regulator (CFTR) mutation DeltaF508CFTR still causes regulatory defects when rescued to the apical membrane, suggesting that the intracellular milieu might affect its ability to respond to cAMP regulation. We recently reported that overexpression of the Na(+)/H(+) exchanger regulatory factor NHERF1 in the cystic fibrosis (CF) airway cell line CFBE41o-rescues the functional expression of DeltaF508CFTR by promoting F-actin organization and formation of the NHERF1-ezrin-actin complex. Here, using real-time FRET reporters of both PKA activity and cAMP levels, we find that lack of an organized subcortical cytoskeleton in CFBE41o-cells causes both defective accumulation of cAMP in the subcortical compartment and excessive cytosolic accumulation of cAMP. This results in reduced subcortical levels and increased cytosolic levels of PKA activity. NHERF1 overexpression in CFBE41o-cells restores chloride secretion, subcortical cAMP compartmentalization and local PKA activity, indicating that regulation of DeltaF508CFTR function requires not only stable expression of the mutant CFTR at the cell surface but also depends on both generation of local cAMP signals of adequate amplitude and activation of PKA in proximity of its target. Moreover, we found that the knockdown of wild-type CFTR in the non-CF 16HBE14o-cells results in both altered cytoskeletal organization and loss of cAMP compartmentalization, whereas stable overexpression of wt CFTR in CF cells restores cytoskeleton organization and re-establishes the compartmentalization of cAMP at the plasma membrane. This suggests that the presence of CFTR on the plasma membrane influences the cytoskeletal organizational state and, consequently, cAMP distribution. Our data show that a sufficiently high concentration of cAMP in the subcortical compartment is required to achieve PKA-mediated regulation of CFTR activity. PMID- 22302989 TI - Altered nanofeature size dictates stem cell differentiation. AB - The differentiation of stem cells can be modulated by physical factors such as the micro- and nano-topography of the extracellular matrix. One important goal in stem cell research is to understand the concept that directs differentiation into a specific cell lineage in the nanoscale environment. Here, we demonstrate that such paths exist by controlling only the micro- and nano-topography of polymer surfaces. Altering the depth (on a nanometric scale) of micro-patterned surface structures allowed increased adhesion of human mesenchymal stem cells (hMSCs) with specific differentiation into osteoblasts, in the absence of osteogenic medium. Small (10 nm) depth patterns promoted cell adhesion without noticeable differentiation, whereas larger depth patterns (100 nm) elicited a collective cell organization, which induced selective differentiation into osteoblast-like cells. This latter response was dictated by stress through focal-adhesion-induced reorganization of F-actin filaments. The results have significant implications for understanding the architectural effects of the in vivo microenvironment and also for the therapeutic use of stem cells. PMID- 22302990 TI - Direct role of Bardet-Biedl syndrome proteins in transcriptional regulation. AB - Primary cilia are conserved organelles that play crucial roles as mechano- and chemosensors, as well as transducing signaling cascades. Consequently, ciliary dysfunction results in a broad range of phenotypes: the ciliopathies. Bardet Biedl syndrome (BBS), a model ciliopathy, is caused by mutations in 16 known genes. However, the biochemical functions of the BBS proteins are not fully understood. Here we show that the BBS7 protein (localized in the centrosomes, basal bodies and cilia) probably has a nuclear role by virtue of the presence of a biologically confirmed nuclear export signal. Consistent with this observation, we show that BBS7 interacts physically with the polycomb group (PcG) member RNF2 and regulate its protein levels, probably through a proteasome-mediated mechanism. In addition, our data supports a similar role for other BBS proteins. Importantly, the interaction with this PcG member is biologically relevant because loss of BBS proteins leads to the aberrant expression of endogenous RNF2 targets in vivo, including several genes that are crucial for development and for cellular and tissue homeostasis. Our data indicate a hitherto unappreciated, direct role for the BBS proteins in transcriptional regulation and potentially expand the mechanistic spectrum that underpins the development of ciliary phenotypes in patients. PMID- 22302991 TI - A dual role for Rac1 GTPases in the regulation of cell motility. AB - Rac proteins are the only canonical Rho family GTPases in Dictyostelium, where they act as key regulators of the actin cytoskeleton. To monitor the dynamics of activated Rac1 in Dictyostelium cells, a fluorescent probe was developed that specifically binds to the GTP-bound form of Rac1. The probe is based on the GTPase-binding domain (GBD) from PAK1 kinase, and was selected on the basis of yeast two-hybrid, GST pull-down and fluorescence resonance energy transfer assays. The PAK1 GBD localizes to leading edges of migrating cells and to endocytotic cups. Similarly to its role in vertebrates, activated Rac1 therefore appears to control de novo actin polymerization at protruding regions of the Dictyostelium cell. Additionally, we found that the IQGAP-related protein DGAP1, which sequesters active Rac1 into a quaternary complex with actin-binding proteins cortexillin I and cortexillin II, localizes to the trailing regions of migrating cells. Notably, PAK1 GBD and DGAP1, which both bind to Rac1-GTP, display mutually exclusive localizations in cell migration, phagocytosis and cytokinesis, and opposite dynamics of recruitment to the cell cortex upon stimulation with chemoattractants. Moreover, cortical localization of the PAK1 GBD depends on the integrity of the actin cytoskeleton, whereas cortical localization of DGAP1 does not. Taken together, these results imply that Rac1 GTPases play a dual role in regulation of cell motility and polarity in Dictyostelium. PMID- 22302992 TI - Localization of glypican-4 in different membrane microdomains is involved in the regulation of Wnt signaling. AB - Glypicans are members of the heparan sulfate proteoglycans (HSPGs) and are involved in various growth factor signaling mechanisms. Although HSPGs affect the beta-catenin-dependent and -independent pathways of Wnt signaling, how they regulate distinct Wnt pathways is not clear. It has been suggested that the beta catenin-dependent pathway is initiated through receptor endocytosis in lipid raft microdomains and the independent pathway is activated through receptor endocytosis in non-lipid raft microdomains. Here, evidence is presented that glypican-4 (GPC4) is localized to both membrane microdomains and that the localization affects its ability to regulate distinct Wnt pathways. GPC4 bound to Wnt3a and Wnt5a, which activate the beta-catenin-dependent and -independent pathways, respectively, and colocalized with Wnts on the cell surface. LRP6, one of Wnt3a coreceptors, was present in lipid raft microdomains, whereas Ror2, one of Wnt5a coreceptors, was localized to non-lipid raft microdomains. Expression of GPC4 enhanced the Wnt3a-dependent beta-catenin pathway and the Wnt5a-dependent beta-catenin-independent pathway, and knockdown of GPC4 suppressed both pathways. A GPC4 mutant that was localized to only non-lipid raft microdomains inhibited the beta-catenin-dependent pathway but enhanced the beta-catenin-independent pathway. These results suggest that GPC4 concentrates Wnt3a and Wnt5a to the vicinity of their specific receptors in different membrane microdomains, thereby regulating distinct Wnt signaling. PMID- 22302993 TI - NF-kappaB regulates protein quality control after heat stress through modulation of the BAG3-HspB8 complex. AB - We previously found that the NF-kappaB transcription factor is activated during the recovery period after heat shock; moreover, we demonstrated that NF-kappaB is essential for cell survival after heat shock by activating autophagy, a mechanism that probably helps the cell to cope with hyperthermic stress through clearance of damaged proteins. In this study, we analyze the involvement of NF-kappaB in basal and heat-stress-induced protein quality control, by comparing the level of multiubiquitylated and/or aggregated proteins, and proteasome and autophagic activity in NF-kappaB-competent and NF-kappaB-incompetent cells. We show that NF kappaB has only a minor role in basal protein quality control, where it modulates autophagosome maturation. By contrast, NF-kappaB is shown to be a key player in protein quality control after hyperthermia. Indeed, NF-kappaB-incompetent cells show highly increased levels of multiubiquitylated and/or aggregated proteins and aggresome clearance defects; a phenotype that disappears when NF-kappaB activity is restored to normal. We demonstrate that during heat shock recovery NF-kappaB activates selective removal of misfolded or aggregated proteins--a process also called 'aggrephagy'--by controlling the expression of BAG3 and HSPB8 and by modulating the level of the BAG3-HspB8 complex. Thus NF-kappaB-mediated increase in the level of the BAG3-HspB8 complex leads to upregulation of aggrephagy and clearance of irreversibly damaged proteins and might increase cell survival in conditions of hyperthermia. PMID- 22302994 TI - GBF1 (Gartenzwerg)-dependent secretion is required for Drosophila tubulogenesis. AB - Here we report on the generation and in vivo analysis of a series of loss-of function mutants for the Drosophila ArfGEF, Gartenzwerg. The Drosophila gene gartenzwerg (garz) encodes the orthologue of mammalian GBF1. garz is expressed ubiquitously in embryos with substantially higher abundance in cells forming diverse tubular structures such as salivary glands, trachea, proventriculus or hindgut. In the absence of functional Garz protein, the integrity of the Golgi complex is impaired. As a result, both vesicle transport of cargo proteins and directed apical membrane delivery are severely disrupted. Dysfunction of the Arf1 COPI machinery caused by a loss of Garz leads to perturbations in establishing a polarized epithelial architecture of tubular organs. Furthermore, insufficient apical transport of proteins and other membrane components causes incomplete luminal diameter expansion and deficiencies in extracellular matrix assembly. The fact that homologues of Garz are present in every annotated metazoan genome indicates that secretion processes mediated by the GBF-type ArfGEFs play a universal role in animal development. PMID- 22302995 TI - GCP6 is a substrate of Plk4 and required for centriole duplication. AB - Centriole duplication occurs once per cell cycle and requires Plk4, a member of the Polo-like kinase family. A key component of the centrosome is the gamma tubulin ring complex (gamma-TuRC) that nucleates microtubules. GCP6 is a member of the gamma-TuRC, but its role in human cells and the regulation of its functions remain unclear. Here we report that depletion of human GCP6 prevents assembly of the gamma-TuRC and induces a high percentage of monopolar spindles. These spindles are characterized by a loss of centrosomal gamma-tubulin and reduced centriole numbers. We found that GCP6 is localized in the pericentriolar material but also at distal portions of centrioles. In addition, GCP6 is required for centriole duplication and Plk4-induced centriole overduplication. GCP6 interacts with and is phosphorylated by Plk4. Moreover, we find that Plk4 dependent phosphorylation of GCP6 regulates centriole duplication. These data suggest that GCP6 is a target of Plk4 in centriole biogenesis. PMID- 22302996 TI - Orai1 deficiency leads to heart failure and skeletal myopathy in zebrafish. AB - Mutations in the store-operated Ca2+ entry pore protein ORAI1 have been reported to cause myopathies in human patients but the mechanism involved is not known. Cardiomyocytes express ORAI1 but its role in heart function is also unknown. Using reverse genetics in zebrafish, we demonstrated that inactivation of the highly conserved zebrafish orthologue of ORAI1 resulted in severe heart failure, reduced ventricular systolic function, bradycardia and skeletal muscle weakness. Electron microscopy of Orai1-deficient myocytes revealed progressive skeletal muscle instability with loss of myofiber integrity and ultrastructural abnormalities of the z-disc in both skeletal and cardiac muscle. Isolated Orai1 deficient cardiomyocytes showed loss of the calcineurin-associated protein calsarcin from the z-discs. Furthermore, we found mechanosignal transduction was affected in Orai1-depleted hearts, indicating an essential role for ORAI1 in establishing the cardiac signaling transduction machinery at the z-disc. Our findings identify ORAI1 as an important regulator of cardiac and skeletal muscle function and provide evidence linking ORAI1-mediated calcium signaling to sarcomere integrity and cardiomyocyte function. PMID- 22302997 TI - Flow cytometry analysis reveals a decrease in intracellular sodium during sperm capacitation. AB - Mammalian sperm require time in the female tract in order to be able to fertilize an egg. The physiological changes that render the sperm able to fertilize are known as capacitation. Capacitation is associated with an increase in intracellular pH, an increase in intracellular calcium and phosphorylation of different proteins. This process is also accompanied by the hyperpolarization of the sperm plasma membrane potential. Recently, we presented evidence showing that epithelial Na+ channels (ENaC) are present in mature sperm and that ENaCs are blocked during capacitation. In the present work, we used flow cytometry to analyze changes in intracellular Na+ concentration ([Na+](i)) during capacitation in individual cells. Our results indicate that capacitated sperm have lower Na+ concentrations. Using sperm with green fluorescent protein in their acrosomes, it was shown that the lower [Na+](i) concentration only occurs in sperm having intact acrosomes. ENaC inhibition has been shown in other cell types to depend on the activation of cystic fibrosis transmembrane conductance regulator (CFTR). In non-capacitated sperm, amiloride, an ENaC inhibitor, and genistein, a CFTR activator, caused a decrease in [Na+](i), suggesting that also in these cells [Na+](i) is dependent on the crosstalk between ENaC and CFTR. In addition, PKA inhibition blocked [Na+](i) decrease in capacitated sperm. Altogether, these data are consistent with the hypothesis that the capacitation-associated hyperpolarization involves a decrease in [Na+](i) mediated by inhibition of ENaC and regulated by PKA through activation of CFTR channels. PMID- 22302998 TI - E-cadherin inhibits nuclear accumulation of Nrf2: implications for chemoresistance of cancer cells. AB - Nrf2 has an anti-carcinogenic effect. However, an increase in Nrf2 activity is also implicated in cancer chemoresistance. A switch from E-cadherin to N-cadherin affects the transdifferentiation and metastasis of cancer cells. In view of the key role of this switch in cancer malignancy, we investigated the regulatory effect of E-cadherin on Nrf2. In HEK293 cells, overexpression of E-cadherin inhibited the nuclear accumulation of Nrf2, and prevented Nrf2-dependent gene induction. GST pull-down and immunocytochemical assays verified the interaction between E-cadherin and Nrf2: E-cadherin bound the C-terminus of Nrf2, but not its N-terminus, which comprises the Neh2 domain responsible for phosphorylation of Ser40. Our finding that the mutation of Ser40 to alanine in Nrf2 did not affect the ability of E-cadherin to bind Nrf2 and repress target gene transactivation suggests that E-cadherin might not disturb the phosphorylation. Studies using mutant constructs of E-cadherin suggested that the beta-catenin-binding domain contributes to the inhibitory effect of E-cadherin on Nrf2. Consistently, knockdown of beta-catenin attenuated not only the effect of E-cadherin binding to Nrf2, but also Keap1-dependent ubiquitylation of Nrf2, and thereby increased Nrf2 activity, supporting the involvement of beta-catenin in the interactions. Collectively, E-cadherin recruits Nrf2 through beta-catenin, and assists the function of Keap1 for the inhibition of nuclear localization and transcriptional activity of Nrf2. In HepG2 cells, the loss of E-cadherin by either siRNA knockdown or treatment with TGFbeta1 enhanced the constitutive or inducible activity of Nrf2, implying that chemoresistance of cancer cells upon the loss of E-cadherin might be associated with Nrf2. PMID- 22302999 TI - Dynamics within tetraspanin pairs affect MHC class II expression. AB - Late endosomal multivesicular bodies (MVBs) are complicated organelles with various subdomains located at the limiting membrane and the internal vesicles (ILVs). ILVs accumulate tetraspanins such as CD63 and CD82 that might form protein assemblies, including major histocompatibility complex class II (MHC-II) and its chaperone human leukocyte antigen (HLA)-DM. Here, we studied the effect of four late endosomal tetraspanin proteins on MHC-II expression. Silencing CD9, CD63 and CD81 enhanced MHC-II expression whereas silencing CD82 did not. No effect on peptide loading was observed. Using confocal FRET technology, we measured the dynamics of CD63 and CD82 interaction with MHC-II and its chaperone HLA-DM. CD63-CD82 interactions remained unaltered in the two MVB subdomains whereas the interactions between CD63 or CD82 homologous pairs changed. CD63 stably associated with MHC-II, and CD82 with HLA-DM, on both MVB subdomains whereas the CD82-MHC-II and CD63-HLA-DM interactions changed. These data visualize for the first time the protein dynamics of tetraspanin assemblies in MVB subdomains. CD63, unlike CD82, stably interacts with MHC-II at both MVB subdomains and controls MHC-II expression. PMID- 22303000 TI - Assembly of Bazooka polarity landmarks through a multifaceted membrane association mechanism. AB - Epithelial cell polarity is essential for animal development. The scaffold protein Bazooka (Baz/PAR-3) forms apical polarity landmarks to organize epithelial cells. However, it is unclear how Baz is recruited to the plasma membrane and how this is coupled with downstream effects. Baz contains an oligomerization domain, three PDZ domains, and binding regions for the protein kinase aPKC and phosphoinositide lipids. With a structure-function approach, we dissected the roles of these domains in the localization and function of Baz in the Drosophila embryonic ectoderm. We found that a multifaceted membrane association mechanism localizes Baz to the apical circumference. Although none of the Baz protein domains are essential for cortical localization, we determined that each contributes to cortical anchorage in a specific manner. We propose that the redundancies involved might provide plasticity and robustness to Baz polarity landmarks. We also identified specific downstream effects, including the promotion of epithelial structure, a positive-feedback loop that recruits aPKC, PAR-6 and Crumbs, and a negative-feedback loop that regulates Baz. PMID- 22303001 TI - Src-mediated phosphorylation of mammalian Abp1 (DBNL) regulates podosome rosette formation in transformed fibroblasts. AB - Podosomes are dynamic actin-based structures that mediate adhesion to the extracellular matrix and localize matrix degradation to facilitate cell motility and invasion. Drebrin-like protein (DBNL), which is homologous to yeast mAbp1 and is therefore known as mammalian actin-binding protein 1 (mAbp1), has been implicated in receptor-mediated endocytosis, vesicle recycling and dorsal ruffle formation. However, it is not known whether mAbp1 regulates podosome formation or cell invasion. In this study, we found that mAbp1 localizes to podosomes and is necessary for the formation of podosome rosettes in Src-transformed fibroblasts. Despite their structural similarity, mAbp1 and cortactin play distinct roles in podosome regulation. Cortactin was necessary for the formation of podosome dots, whereas mAbp1 was necessary for the formation of organized podosome rosettes in Src-transformed cells. We identified specific Src phosphorylation sites, Tyr337 and Tyr347 of mAbp1, which mediate the formation of podosome rosettes and degradation of the ECM. In contrast to dorsal ruffles, the interaction of mAbp1 with WASP-interacting protein (WIP) was not necessary for the formation of podosome rosettes. Finally, we showed that depletion of mAbp1 increased invasive cell migration, suggesting that mAbp1 differentially regulates matrix degradation and cell invasion. Collectively, our findings identify a role for mAbp1 in podosome rosette formation and cell invasion downstream of Src. PMID- 22303002 TI - Sphingolipid-modulated exosome secretion promotes clearance of amyloid-beta by microglia. AB - Amyloid beta-peptide (Abeta), the pathogenic agent of Alzheimer disease, is a physiological metabolite whose levels are constantly controlled in normal brain. Recent studies have demonstrated that a fraction of extracellular Abeta is associated with exosomes, small membrane vesicles of endosomal origin, although the fate of Abeta in association with exosome is largely unknown. In this study, we identified novel roles for neuron-derived exosomes acting on extracellular Abeta, i.e. exosomes drive conformational changes in Abeta to form nontoxic amyloid fibrils and promote uptake of Abeta by microglia. The Abeta internalized together with exosomes was further transported to lysosomes and degraded. We also found that blockade of phosphatidylserine on the surface of exosomes by annexin V not only prevented exosome uptake but also suppressed Abeta incorporation into microglia. In addition, we demonstrated that secretion of neuron-derived exosomes was modulated by the activities of sphingolipid-metabolizing enzymes, including neutral sphingomyelinase 2 (nSMase2) and sphingomyelin synthase 2 (SMS2). In transwell experiments, up-regulation of exosome secretion from neuronal cells by treatment with SMS2 siRNA enhanced Abeta uptake into microglial cells and significantly decreased extracellular levels of Abeta. Our findings indicate a novel mechanism responsible for clearance of Abeta through its association with exosomes. The modulation of the vesicle release and/or elimination may alter the risk of AD. PMID- 22303003 TI - Platelet-activating factor receptor agonists mediate xeroderma pigmentosum A photosensitivity. AB - To date, oxidized glycerophosphocholines (Ox-GPCs) with platelet-activating factor (PAF) activity produced non-enzymatically have not been definitively demonstrated to mediate any known disease processes. Here we provide evidence that these Ox-GPCs play a pivotal role in the photosensitivity associated with the deficiency of the DNA repair protein xeroderma pigmentosum type A (XPA). It should be noted that XPA-deficient cells are known to have decreased antioxidant defenses. These studies demonstrate that treatment of human XPA-deficient fibroblasts with the pro-oxidative stressor ultraviolet B (UVB) radiation resulted in increased reactive oxygen species and PAF receptor (PAF-R) agonistic activity in comparison with gene-corrected cells. The UVB irradiation-generated PAF-R agonists were inhibited by antioxidants. UVB irradiation of XPA-deficient (Xpa-/-) mice also resulted in increased PAF-R agonistic activity and skin inflammation in comparison with control mice. The increased UVB irradiation mediated skin inflammation and TNF-alpha production in Xpa-/- mice were blocked by systemic antioxidants and by PAF-R antagonists. Structural characterization of PAF-R-stimulating activity in UVB-irradiated XPA-deficient fibroblasts using mass spectrometry revealed increased levels of sn-2 short-chain Ox-GPCs along with native PAF. These studies support a critical role for PAF-R agonistic Ox-GPCs in the pathophysiology of XPA photosensitivity. PMID- 22303004 TI - Phosphorylation of Sar1b protein releases liver fatty acid-binding protein from multiprotein complex in intestinal cytosol enabling it to bind to endoplasmic reticulum (ER) and bud the pre-chylomicron transport vesicle. AB - Native cytosol requires ATP to initiate the budding of the pre-chylomicron transport vesicle from intestinal endoplasmic reticulum (ER). When FABP1 alone is used, no ATP is needed. Here, we test the hypothesis that in native cytosol FABP1 is present in a multiprotein complex that prevents FABP1 binding to the ER unless the complex is phosphorylated. We found on chromatography of native intestinal cytosol over a Sephacryl S-100 HR column that FABP1 (14 kDa) eluted in a volume suggesting a 75-kDa protein complex that contained four proteins on an anti-FABP1 antibody pulldown. The FABP1-containing column fractions were chromatographed over an anti-FABP1 antibody adsorption column. Proteins co-eluted from the column were identified as FABP1, Sar1b, Sec13, and small VCP/p97-interactive protein by immunoblot, LC-MS/MS, and MALDI-TOF. The four proteins of the complex had a total mass of 77 kDa and migrated on native PAGE at 75 kDa. When the complex was incubated with intestinal ER, there was no increase in FABP1-ER binding. However, when the complex member Sar1b was phosphorylated by PKCzeta and ATP, the complex completely disassembled into its component proteins that migrated at their monomer molecular weight on native PAGE. FABP1, freed from the complex, was now able to bind to intestinal ER and generate the pre-chylomicron transport vesicle (PCTV). No increase in ER binding or PCTV generation was observed in the absence of PKCzeta or ATP. We conclude that phosphorylation of Sar1b disrupts the FABP1 containing four-membered 75-kDa protein complex in cytosol enabling it to bind to the ER and generate PCTV. PMID- 22303005 TI - Structural requirements of membrane phospholipids for M-type potassium channel activation and binding. AB - M-channels are voltage-gated potassium channels that regulate cell excitability. They are heterotetrameric assemblies of Kv7.2 and Kv7.3 subunits. Their opening requires the presence of the membrane phospholipid phosphatidylinositol 4,5 bisphosphate (PI(4,5)P(2)). However, the specificity of PI(4,5)P(2) as a binding and activating ligand is unknown. Here, we tested the ability of different phosphoinositides and lipid phosphates to activate or bind to M-channel proteins. Activation of functional channels was measured in membrane patches isolated from cells coexpressing Kv7.2 and Kv7.3 subunits. Channels were activated to similar extents (maximum open probability of ~0.8 at 0 mV) by 0.1-300 MUM dioctanoyl homologs of the three endogenous phosphoinositides, PI(4)P, PI(4,5)P(2), and PI(3,4,5)P(3), with sensitivity increasing with increasing numbers of phosphates. Non-acylated inositol phosphates had no effect up to 100 MUM. Channels were also activated with increasing efficacy by 1-300 MUM concentrations of the monoacyl monophosphates fingolimod phosphate, sphingosine 1-phosphate, and lysophosphatidic acid but not by phosphate-free fingolimod or sphingosine or by phosphate-masked phosphatidylcholine or phosphatidylglycerol. An overlay assay confirmed that a fusion protein containing the full-length C terminus of Kv7.2 could bind to a broad range of phosphoinositides and phospholipids. A mutated Kv7.2 C-terminal construct with reduced sensitivity to PI(4,5)P showed significantly less binding to most polyphosphoinositides. We concluded that M channels bind to, and are activated by, a wide range of lipid phosphates, with a minimum requirement for an acyl chain and a phosphate headgroup. In this, they more closely resemble inwardly rectifying Kir6.2 potassium channels than the more PI(4,5)P(2)-specific Kir2 channels. Notwithstanding, the data also support the view that the main endogenous activator of M-channels is PI(4,5)P(2). PMID- 22303006 TI - Heme utilization in the Caenorhabditis elegans hypodermal cells is facilitated by heme-responsive gene-2. AB - The roundworm Caenorhabditis elegans is a heme auxotroph that requires the coordinated actions of HRG-1 heme permeases to transport environmental heme into the intestine and HRG-3, a secreted protein, to deliver intestinal heme to other tissues including the embryo. Here we show that heme homeostasis in the extraintestinal hypodermal tissue was facilitated by the transmembrane protein HRG-2. Systemic heme deficiency up-regulated hrg-2 mRNA expression over 200-fold in the main body hypodermal syncytium, hyp 7. HRG-2 is a type I membrane protein that binds heme and localizes to the endoplasmic reticulum and apical plasma membrane. Cytochrome heme profiles are aberrant in HRG-2-deficient worms, a phenotype that was partially suppressed by heme supplementation. A heme-deficient yeast strain, ectopically expressing worm HRG-2, revealed significantly improved growth at submicromolar concentrations of exogenous heme. Taken together, our results implicate HRG-2 as a facilitator of heme utilization in the Caenorhabditis elegans hypodermis and provide a mechanism for the regulation of heme homeostasis in an extraintestinal tissue. PMID- 22303007 TI - Direct role for proliferating cell nuclear antigen in substrate recognition by the E3 ubiquitin ligase CRL4Cdt2. AB - The E3 ubiquitin ligase Cullin-ring ligase 4-Cdt2 (CRL4(Cdt2)) is emerging as an important cell cycle regulator that targets numerous proteins for destruction in S phase and after DNA damage, including Cdt1, p21, and Set8. CRL4(Cdt2) substrates contain a "PIP degron," which consists of a canonical proliferating cell nuclear antigen (PCNA) interaction motif (PIP box) and an adjacent basic amino acid. Substrates use their PIP box to form a binary complex with PCNA on chromatin and the basic residue to recruit CRL4(Cdt2) for substrate ubiquitylation. Using Xenopus egg extracts, we identify an acidic residue in PCNA that is essential to support destruction of all CRL4(Cdt2) substrates. This PCNA residue, which adjoins the basic amino acid of the bound PIP degron, is dispensable for substrate binding to PCNA but essential for CRL4(Cdt2) recruitment to chromatin. Our data show that the interaction of CRL4(Cdt2) with substrates requires molecular determinants not only in the substrate degron but also on PCNA. The results illustrate a potentially general mechanism by which E3 ligases can couple ubiquitylation to the formation of protein-protein interactions. PMID- 22303008 TI - Bacterial degradation of benzoate: cross-regulation between aerobic and anaerobic pathways. AB - We have studied for the first time the transcriptional regulatory circuit that controls the expression of the box genes encoding the aerobic hybrid pathway used to assimilate benzoate via coenzyme A (CoA) derivatives in bacteria. The promoters responsible for the expression of the box cluster in the beta proteobacterium Azoarcus sp., their cognate transcriptional repressor, the BoxR protein, and the inducer molecule (benzoyl-CoA) have been characterized. The BoxR protein shows a significant sequence identity to the BzdR transcriptional repressor that controls the bzd genes involved in the anaerobic degradation of benzoate. Because the boxR gene is present in all box clusters so far identified in bacteria, the BoxR/benzoyl-CoA regulatory system appears to be a widespread strategy to control this aerobic hybrid pathway. Interestingly, the paralogous BoxR and BzdR regulators act synergistically to control the expression of the box and bzd genes. This cross-regulation between anaerobic and aerobic pathways for the catabolism of aromatic compounds has never been shown before, and it may reflect a biological strategy to increase the cell fitness in organisms that survive in environments subject to changing oxygen concentrations. PMID- 22303009 TI - Protein interacting with C kinase 1 (PICK1) reduces reinsertion rates of interaction partners sorted to Rab11-dependent slow recycling pathway. AB - The scaffolding protein PICK1 (protein interacting with C kinase 1) contains an N terminal PSD-95/Discs large/ZO-1 (PDZ) domain and a central lipid-binding Bin/amphiphysin/Rvs (BAR) domain. PICK1 is thought to regulate trafficking of its PDZ binding partners but different and even opposing functions have been suggested. Here, we apply ELISA-based assays and confocal microscopy in HEK293 cells with inducible PICK1 expression to assess in an isolated system the ability of PICK1 to regulate trafficking of natural and engineered PDZ binding partners. The dopamine transporter (DAT), which primarily sorts to degradation upon internalization, did not form perinuclear clusters with PICK1, and PICK1 did not affect DAT internalization/recycling. However, transfer of the PICK1-binding DAT C terminus to the beta(2)-adrenergic receptor, which sorts to recycling upon internalization, led to formation of PICK1 co-clusters in Rab11-positive compartments. Furthermore, PICK1 inhibited Rab11-mediated recycling of the receptor in a BAR and PDZ domain-dependent manner. In contrast, transfer of the DAT C terminus to the delta-opioid receptor, which sorts to degradation, did not result in PICK1 co-clusters or any change in internalization/recycling. Further support for a role of PICK1 determined by its PDZ cargo was obtained for the PICK1 interaction partner prolactin-releasing peptide receptor (GPR10). GPR10 co localized with Rab11 and clustered with PICK1 upon constitutive internalization but co-localized with the late endosomal marker Rab7 and did not cluster with PICK1 upon agonist-induced internalization. Our data suggest a selective role of PICK1 in clustering and reducing the recycling rates of PDZ domain binding partners sorted to the Rab11-dependent recycling pathway. PMID- 22303010 TI - During replication stress, non-SMC element 5 (NSE5) is required for Smc5/6 protein complex functionality at stalled forks. AB - The Smc5/6 complex belongs to the SMC (structural maintenance of chromosomes) family, which also includes cohesin and condensin. In Saccharomyces cerevisiae, the Smc5/6 complex contains six essential non-Smc elements, Nse1-6. Very little is known about how these additional elements contribute to complex function except for Nse2/Mms21, which is an E3 small ubiquitin-like modifier (SUMO) ligase important for Smc5 sumoylation. Characterization of two temperature-sensitive mutants, nse5-ts1 and nse5-ts2, demonstrated the importance of Nse5 within the Smc5/6 complex for its stability and functionality at forks during hydroxyurea induced replication stress. Both NSE5 alleles showed a marked reduction in Smc5 sumoylation to levels lower than those observed with mms21-11, a mutant of Mms21 that is deficient in SUMO ligase activity. However, a phenotypic comparison of nse5-ts1 and nse5-ts2 revealed a separation of importance between Smc5 sumoylation and the function of the Smc5/6 complex during replication. Only cells carrying the nse5-ts1 allele exhibited defects such as dissociation of the replisome from stalled forks, formation of fork-associated homologous recombination intermediates, and hydroxyurea sensitivity that is additive with mms21-11. These defects are attributed to a failure in Smc5/6 localization to forks in nse5-ts1 cells. Overall, these data support the premise that Nse5 is important for vital interactions between components within the Smc5/6 complex, and for its functionality during replication stress. PMID- 22303011 TI - Crystal structure of mitochondrial fission complex reveals scaffolding function for mitochondrial division 1 (Mdv1) coiled coil. AB - The mitochondrial fission machinery is best understood in the yeast Saccharomyces cerevisiae, where Fis1, Mdv1, and Dnm1 are essential components. Fis1 is a mitochondrial outer membrane protein that recruits the dynamin-related GTPase Dnm1 during the fission process. This recruitment occurs via Mdv1, which binds both Fis1 and Dnm1 and therefore functions as a molecular adaptor linking the two molecules. Mdv1 has a modular structure, consisting of an N-terminal extension that binds Fis1, a central coiled coil for dimerization, and a C-terminal WD40 repeat region that binds Dnm1. We have solved the crystal structure of a dimeric Mdv1-Fis1 complex that contains both the N-terminal extension and coiled-coil regions of Mdv1. Consistent with previous studies, Mdv1 binds Fis1 through a U shaped helix-loop-helix motif, and dimerization of the Mdv1-Fis1 complex is mediated by the antiparallel coiled coil of Mdv1. However, the complex is surprisingly compact and rigid due to two additional contacts mediated by the surface of the Mdv1 coiled coil. The coiled coil packs against both Fis1 and the second helix of the Mdv1 helix-loop-helix motif. Mutational analyses showed that these contacts are important for mitochondrial fission activity. These results indicate that, in addition to dimerization, the unusually long Mdv1 coiled coil serves a scaffolding function to stabilize the Mdv1-Fis1 complex. PMID- 22303012 TI - Alternating access to the transmembrane domain of the ATP-binding cassette protein cystic fibrosis transmembrane conductance regulator (ABCC7). AB - The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is a member of the ATP-binding cassette (ABC) protein family, most members of which act as active transporters. Actively transporting ABC proteins are thought to alternate between "outwardly facing" and "inwardly facing" conformations of the transmembrane substrate pathway. In CFTR, it is assumed that the outwardly facing conformation corresponds to the channel open state, based on homology with other ABC proteins. We have used patch clamp recording to quantify the rate of access of cysteine-reactive probes to cysteines introduced into two different transmembrane regions of CFTR from both the intracellular and extracellular solutions. Two probes, the large [2-sulfonatoethyl]methanethiosulfonate (MTSES) molecule and permeant Au(CN)(2)(-) ions, were applied to either side of the membrane to modify cysteines substituted for Leu-102 (first transmembrane region) and Thr-338 (sixth transmembrane region). Channel opening and closing were altered by mutations in the nucleotide binding domains of the channel. We find that, for both MTSES and Au(CN)(2)(-), access to these two cysteines from the cytoplasmic side is faster in open channels, whereas access to these same sites from the extracellular side is faster in closed channels. These results are consistent with alternating access to the transmembrane regions, however with the open state facing inwardly and the closed state facing outwardly. Our findings therefore prompt revision of current CFTR structural and mechanistic models, as well as having broader implications for transport mechanisms in all ABC proteins. Our results also suggest possible locations of both functional and dysfunctional ("vestigial") gates within the CFTR permeation pathway. PMID- 22303013 TI - Two distinct states of Escherichia coli cells that overexpress recombinant heterogeneous beta-galactosidase. AB - The mechanism by which inclusion bodies form is still not well understood, partly because the dynamic processes of the inclusion body formation and its solubilization have hardly been investigated at an individual cell level, and so the important detailed information has not been acquired for the mechanism. In this study, we investigated the in vivo folding and aggregation of Aspergillus phoenicis beta-D-galactosidase fused to a red fluorescence protein in individual Escherichia coli cells. The folding status and expression level of the recombinant beta-D-galactosidase at an individual cell level was analyzed by flow cytometry in combination with transmission electron microscopy and Western blotting. We found that individual E. coli cells fell into two distinct states, one containing only inclusion bodies accompanied with low galactosidase activity and the other containing the recombinant soluble galactosidase accompanied with high galactosidase activity. The majority of the E. coli cells in the later state possessed no inclusion bodies. The two states of the cells were shifted to a cell state with high enzyme activity by culturing the cells in isopropyl 1-thio-beta-D galactopyranoside-free medium after an initial protein expression induction in isopropyl 1-thio-beta-D-galactopyranoside-containing medium. This shift of the cell population status took place without the level change of the beta-D galactosidase protein in individual cells, indicating that the factor(s) besides the crowdedness of the recombinant protein play a major role in the cell state transition. These results shed new light on the mechanism of inclusion body formation and will facilitate the development of new strategies in improving recombinant protein quality. PMID- 22303014 TI - Interconnection of salt-induced hydrophobic compaction and secondary structure formation depends on solution conditions: revisiting early events of protein folding at single molecule resolution. AB - What happens in the early stage of protein folding remains an interesting unsolved problem. Rapid kinetics measurements with cytochrome c using submillisecond continuous flow mixing devices suggest simultaneous formation of a compact collapsed state and secondary structure. These data seem to indicate that collapse formation is guided by specific short and long range interactions (heteropolymer collapse). A contrasting interpretation also has been proposed, which suggests that the collapse formation is rapid, nonspecific, and a trivial solvent related compaction, which could as well be observed by a homopolymer (homopolymer collapse). We address this controversy using fluorescence correlation spectroscopy (FCS), which enables us to monitor the salt-induced compaction accompanying collapse formation and the associated time constant directly at single molecule resolution. In addition, we follow the formation of secondary structure using far UV CD. The data presented here suggest that both these models (homopolymer and heteropolymer) could be applicable depending on the solution conditions. For example, the formation of secondary structure and compact state is not simultaneous in aqueous buffer. In aqueous buffer, formation of the compact state occurs through a two-state co-operative transition following heteropolymer formalism, whereas secondary structure formation takes place gradually. In contrast, in the presence of urea, a compaction of the protein radius occurs gradually over an extended range of salt concentration following homopolymer formalism. The salt-induced compaction and the formation of secondary structure take place simultaneously in the presence of urea. PMID- 22303015 TI - GABRB3 mutation, G32R, associated with childhood absence epilepsy alters alpha1beta3gamma2L gamma-aminobutyric acid type A (GABAA) receptor expression and channel gating. AB - A GABA(A) receptor beta3 subunit mutation, G32R, has been associated with childhood absence epilepsy. We evaluated the possibility that this mutation, which is located adjacent to the most N-terminal of three beta3 subunit N glycosylation sites, might reduce GABAergic inhibition by increasing glycosylation of beta3 subunits. The mutation had three major effects on GABA(A) receptors. First, coexpression of beta3(G32R) subunits with alpha1 or alpha3 and gamma2L subunits in HEK293T cells reduced surface expression of gamma2L subunits and increased surface expression of beta3 subunits, suggesting a partial shift from ternary alphabeta3gamma2L receptors to binary alphabeta3 and homomeric beta3 receptors. Second, beta3(G32R) subunits were more likely than beta3 subunits to be N-glycosylated at Asn-33, but increases in glycosylation were not responsible for changes in subunit surface expression. Rather, both phenomena could be attributed to the presence of a basic residue at position 32. Finally, alpha1beta3(G32R)gamma2L receptors had significantly reduced macroscopic current density. This reduction could not be explained fully by changes in subunit expression levels (because gamma2L levels decreased only slightly) or glycosylation (because reduction persisted in the absence of glycosylation at Asn 33). Single channel recording revealed that alpha1beta3(G32R)gamma2L receptors had impaired gating with shorter mean open time. Homology modeling indicated that the mutation altered salt bridges at subunit interfaces, including regions important for subunit oligomerization. Our results suggest both a mechanism for mutation-induced hyperexcitability and a novel role for the beta3 subunit N terminal alpha-helix in receptor assembly and gating. PMID- 22303016 TI - Determinants of murein hydrolase targeting to cross-wall of Staphylococcus aureus peptidoglycan. AB - Cells of eukaryotic or prokaryotic origin express proteins with LysM domains that associate with the cell wall envelope of bacteria. The molecular properties that enable LysM domains to interact with microbial cell walls are not yet established. Staphylococcus aureus, a spherical microbe, secretes two murein hydrolases with LysM domains, Sle1 and LytN. We show here that the LysM domains of Sle1 and LytN direct murein hydrolases to the staphylococcal envelope in the vicinity of the cross-wall, the mid-cell compartment for peptidoglycan synthesis. LysM domains associate with the repeating disaccharide beta-N-acetylmuramic acid, (1->4)-beta-N-acetylglucosamine of staphylococcal peptidoglycan. Modification of N-acetylmuramic acid with wall teichoic acid, a ribitol-phosphate polymer tethered to murein linkage units, prevents the LysM domain from binding to peptidoglycan. The localization of LytN and Sle1 to the cross-wall is abolished in staphylococcal tagO mutants, which are defective for wall teichoic acid synthesis. We propose a model whereby the LysM domain ensures septal localization of LytN and Sle1 followed by processive cleavage of peptidoglycan, thereby exposing new LysM binding sites in the cross-wall and separating bacterial cells. PMID- 22303017 TI - Structural basis for antifreeze activity of ice-binding protein from arctic yeast. AB - Arctic yeast Leucosporidium sp. produces a glycosylated ice-binding protein (LeIBP) with a molecular mass of ~25 kDa, which can lower the freezing point below the melting point once it binds to ice. LeIBP is a member of a large class of ice-binding proteins, the structures of which are unknown. Here, we report the crystal structures of non-glycosylated LeIBP and glycosylated LeIBP at 1.57- and 2.43-A resolution, respectively. Structural analysis of the LeIBPs revealed a dimeric right-handed beta-helix fold, which is composed of three parts: a large coiled structural domain, a long helix region (residues 96-115 form a long alpha helix that packs along one face of the beta-helix), and a C-terminal hydrophobic loop region ((243)PFVPAPEVV(251)). Unexpectedly, the C-terminal hydrophobic loop region has an extended conformation pointing away from the body of the coiled structural domain and forms intertwined dimer interactions. In addition, structural analysis of glycosylated LeIBP with sugar moieties attached to Asn(185) provides a basis for interpreting previous biochemical analyses as well as the increased stability and secretion of glycosylated LeIBP. We also determined that the aligned Thr/Ser/Ala residues are critical for ice binding within the B face of LeIBP using site-directed mutagenesis. Although LeIBP has a common beta-helical fold similar to that of canonical hyperactive antifreeze proteins, the ice-binding site is more complex and does not have a simple ice binding motif. In conclusion, we could identify the ice-binding site of LeIBP and discuss differences in the ice-binding modes compared with other known antifreeze proteins and ice-binding proteins. PMID- 22303018 TI - Constitutive production of catalytic antibodies to a Staphylococcus aureus virulence factor and effect of infection. AB - Antibodies that recognize microbial B lymphocyte superantigenic epitopes are produced constitutively with no requirement for adaptive immune maturation. We report cleavage of the Staphylococcus aureus virulence factor extracellular fibrinogen-binding protein (Efb) by catalytic antibodies produced with no exposure to the bacterium and reduction of the catalytic antibody activity following infection. IgG catalytic antibodies that specifically hydrolyzed Efb via a nucleophilic catalytic mechanism were found in the blood of healthy humans and aseptic mice free of S. aureus infection. IgG hydrolyzed peptide bonds on the C-terminal side of basic amino acids, including a bond located within the C3b binding domain of Efb. Efb digested with the IgG lost its ability to bind C3b and inhibit complement-dependent antibody-mediated red blood cell lysis. In addition to catalysis, the IgG expressed saturable Efb binding activity. IgG from S. aureus-infected mice displayed reduced Efb cleaving activity and increased Efb binding activity compared with uninfected controls, suggesting differing effects of the infection on the antibody subsets responsible for the two activities. IgG from children hospitalized for S. aureus infection also displayed reduced Efb cleavage compared with healthy children. These data suggest a potential defense function for constitutively produced catalytic antibodies to a putative superantigenic site of Efb, but an adaptive catalytic response appears to be proscribed. PMID- 22303019 TI - Curcumin suppresses T cell activation by blocking Ca2+ mobilization and nuclear factor of activated T cells (NFAT) activation. AB - Curcumin is the active ingredient of the spice turmeric and has been shown to have a number of pharmacologic and therapeutic activities including antioxidant, anti-microbial, anti-inflammatory, and anti-carcinogenic properties. The anti inflammatory effects of curcumin have primarily been attributed to its inhibitory effect on NF-kappaB activity due to redox regulation. In this study, we show that curcumin is an immunosuppressive phytochemical that blocks T cell-activation induced Ca(2+) mobilization with IC(50) = ~12.5 MUM and thereby prevents NFAT activation and NFAT-regulated cytokine expression. This finding provides a new mechanism for curcumin-mediated anti-inflammatory and immunosuppressive function. We also show that curcumin can synergize with CsA to enhance immunosuppressive activity because of different inhibitory mechanisms. Furthermore, because Ca(2+) is also the secondary messenger crucial for the TCR-induced NF-kappaB signaling pathway, our finding also provides another mechanism by which curcumin suppresses NF-kappaB activation. PMID- 22303020 TI - Novel bacterial lipoprotein structures conserved in low-GC content gram-positive bacteria are recognized by Toll-like receptor 2. AB - Bacterial lipoproteins/lipopeptides inducing host innate immune responses are sensed by mammalian Toll-like receptor 2 (TLR2). These bacterial lipoproteins are structurally divided into two groups, diacylated or triacylated lipoproteins, by the absence or presence of an amide-linked fatty acid. The presence of diacylated lipoproteins has been predicted in low-GC content gram-positive bacteria and mycoplasmas based on the absence of one modification enzyme in their genomes; however, we recently determined triacylated structures in low-GC gram-positive Staphylococcus aureus, raising questions about the actual lipoprotein structure in other low-GC content gram-positive bacteria. Here, through intensive MS analyses, we identified a novel and unique bacterial lipoprotein structure containing an N-acyl-S-monoacyl-glyceryl-cysteine (named the lyso structure) from low-GC gram-positive Enterococcus faecalis, Bacillus cereus, Streptococcus sanguinis, and Lactobacillus bulgaricus. Two of the purified native lyso-form lipoproteins induced proinflammatory cytokine production from mice macrophages in a TLR2-dependent and TLR1-independent manner but with a different dependence on TLR6. Additionally, two other new lipoprotein structures were identified. One is the "N-acetyl" lipoprotein structure containing N-acetyl-S-diacyl-glyceryl cysteine, which was found in five gram-positive bacteria, including Bacillus subtilis. The N-acetyl lipoproteins induced the proinflammatory cytokines through the TLR2/6 heterodimer. The other was identified in a mycoplasma strain and is an unusual diacyl lipoprotein structure containing two amino acids before the lipid modified cysteine residue. Taken together, our results suggest the existence of novel TLR2-stimulating lyso and N-acetyl forms of lipoproteins that are conserved in low-GC content gram-positive bacteria and provide clear evidence for the presence of yet to be identified key enzymes involved in the bacterial lipoprotein biosynthesis. PMID- 22303021 TI - The vital role of polymerase zeta and REV1 in mutagenic, but not correct, DNA synthesis across benzo[a]pyrene-dG and recruitment of polymerase zeta by REV1 to replication-stalled site. AB - The DNA synthesis across DNA lesions, termed translesion synthesis (TLS), is a complex process influenced by various factors. To investigate this process in mammalian cells, we examined TLS across a benzo[a]pyrene dihydrodiol epoxide derived dG adduct (BPDE-dG) using a plasmid bearing a single BPDE-dG and genetically engineered mouse embryonic fibroblasts (MEFs). In wild-type MEFs, TLS was extremely miscoding (>90%) with G -> T transversions being predominant. Knockout of the Rev1 gene decreased both the TLS efficiency and the miscoding frequency. Knockout of the Rev3L gene, coding for the catalytic subunit of pol zeta, caused even greater decreases in these two TLS parameters; almost all residual TLS were error-free. Thus, REV1 and pol zeta are critical to mutagenic, but not accurate, TLS across BPDE-dG. The introduction of human REV1 cDNA into Rev1(-/-) MEFs restored the mutagenic TLS, but a REV1 mutant lacking the C terminus did not. Yeast and mammalian three-hybrid assays revealed that the REV7 subunit of pol zeta mediated the interaction between REV3 and the REV1 C terminus. These results support the hypothesis that REV1 recruits pol zeta through the interaction with REV7. Our results also predict the existence of a minor REV1-independent pol zeta recruitment pathway. Finally, although mutagenic TLS across BPDE-dG largely depends on RAD18, experiments using Polk(-/-) Polh(-/ ) Poli(-/-) triple-gene knockout MEFs unexpectedly revealed that another polymerase(s) could insert a nucleotide opposite BPDE-dG. This indicates that a non-Y family polymerase(s) can insert a nucleotide opposite BPDE-dG, but the subsequent extension from miscoding termini depends on REV1-polzeta in a RAD18 dependent manner. PMID- 22303022 TI - Assembly, purification, and pre-steady-state kinetic analysis of active RNA dependent RNA polymerase elongation complex. AB - NS5B is the RNA-dependent RNA polymerase responsible for replicating hepatitis C virus (HCV) genomic RNA. Despite more than a decade of work, the formation of a highly active NS5B polymerase.RNA complex suitable for mechanistic and structural studies has remained elusive. Here, we report that through a novel way of optimizing initiation conditions, we were able to generate a productive NS5B.primer.template elongation complex stalled after formation of a 9-nucleotide primer. In contrast to previous reports of very low proportions of active NS5B, we observed that under optimized conditions up to 65% of NS5B could be converted into active elongation complexes. The elongation complex was extremely stable, allowing purification away from excess nucleotide and abortive initiation products so that the purified complex was suitable for pre-steady-state kinetic analyses of polymerase activity. Single turnover kinetic studies showed that CTP is incorporated with apparent K(d) and k(pol) values of 39 +/- 3 MUM and 16 +/- 1 s(-1), respectively, giving a specificity constant of k(pol)/K(d) of 0.41 MUM(-1) s(-1). The kinetics of multiple nucleotide incorporation during processive elongation also were determined. This work establishes a novel way to generate a highly active elongation complex of the medically important NS5B polymerase for structural and functional studies. PMID- 22303023 TI - Right hemifield deficits in judging simultaneity: a perceptual learning study. AB - Prior reports demonstrate that simultaneity is judged less precisely in the right visual field (RVF) than in the left visual field (LVF). The present psychophysical study was conducted to provide new information about why and when (i.e., the visual information stage at which) RVF deficits arise in simultaneity judgments. In Experiment 1, participants judged either the simultaneity or the relative spatial frequency of Gabor targets in the right or left hemifield while distractors were randomly absent or present. When attention was not needed to exclude distractors, signal detection theory analyses revealed an RVF simultaneity deficit with an error pattern that implicates low RVF temporal acuity, not excessive RVF neural noise. Adding attentionally demanding distractors introduced a separate, significant RVF simultaneity deficit with error patterns that implicate the inappropriate integration of temporal asynchronies from distractor locations. Neither the distractor-independent RVF acuity deficit nor the distractor-induced RVF excessive spatial integration occurred for spatial frequency discrimination at the same retinal locations. In Experiment 2, a perceptual learning procedure significantly improved RVF simultaneity judgments. The learning was task-specific but generalized to the untrained (left) visual field and to novel retinal locations. This observation implicates the simultaneity decision as the visual information stage that sets the limit on performance. PMID- 22303024 TI - Wide two-dimensional field laser ray-tracing aberrometer. AB - There is an increasing interest in measuring the peripheral optical quality of the eye. Optical aberrations have been studied extensively in the center of the visual field due to the development of Hartmann-Shack wavefront sensor. However, experimental data of the peripheral field of view are still scarce, partly due to the fact that this evaluation presents various challenges. Here, we propose a novel device based on the laser ray-tracing (LRT) aberrometer, which is well suited for measuring the off-axis aberrations. The proposed instrument is able to measure a wide (+/-40 degrees ) 2D visual field and is based on three main design principles: spiral-shaped sampling of the visual field, real-time detection of the eye's entrance pupil, and automatic shaping and delivering of the ray bundle that optimally samples the eye pupil. We present experimental data obtained on 11 healthy subjects and a novel analysis based on a 2D quadratic model of the aberrations as a function of visual field and azimuth. The obtained results are consistent with previous findings. PMID- 22303028 TI - Recommended childhood and adolescent immunization schedules--United States, 2012. PMID- 22303032 TI - Ecstasy (MDMA)-induced hyponatraemia is associated with genetic variants in CYP2D6 and COMT. AB - We hypothesised that genetically determined poor metabolism of 3,4-methylene dioxymetamphetamine (MDMA) due either to the presence of CYP2D6 genotypes giving absent or low CYP2D6 enzyme activity, or a COMT genotype predicting low COMT enzyme activity would be associated with a greater degree of MDMA-induced reduction in plasma sodium and osmolality than other genotypes at these genes following consumption of 'ecstasy' tablets by clubbers. Of the 48 subjects who returned to the test site post-clubbing, 30 provided samples for measurement of vasopressin (AVP), plasma sodium, urea and plasma and urine osmolality. Genotyping was performed for functional variants in CYP2D6 (n = 29) and COMT (Val158Met, n = 30). In subjects with urinary MDMA detected post-clubbing, there was a significant association between change in plasma osmolality (p = 0.009) and in plasma sodium (p = 0.012) and CYP2D6 genotypic category. Individuals with the low-activity but readily inhibitable CYP2D6 extensive metaboliser/intermediate metaboliser (EM/IM) genotype showed greater reductions in these measures than all other CYP2D6 genotypic categories. COMT low-activity genotypes (Met/Met and Val/Met) were also significantly associated with reductions in plasma osmolality (p = 0.028) and in plasma sodium (p = 0.003). On conservative Bonferroni correction for two independent genes, the CYP2D6 and COMT plasma sodium findings remain significant. The relatively high frequency of the low-activity CYP2D6 and COMT genotypes in the population warrants further attention, since consumption of free water following ingestion of MDMA in these individuals may trigger dilutational hyponatraemia and increased risk of syndrome of inappropriate antidiuretic hormone secretion. PMID- 22303033 TI - Substance-Related Knowledge, Attitude, and Behavior among College Students: Opportunities for Health Education. AB - OBJECTIVE: To examine substance-related attitudes and behaviors among college students across an academic semester. DESIGN: Pre-post quasi-experimental survey design. SETTING: A large Midwestern University. METHOD: Surveys were completed by 299 undergraduates enrolled in three courses: drugs and behavior, abnormal psychology, and normal personality theories. RESULTS: Although students enrolled in the drug course were not more knowledgeable about drugs than others at baseline, their knowledge increased by semester's end, while the others' did not. Perceived prevalence of alcohol use was more accurate and became increasingly accurate among drugs and behavior students. Class enrollment, gender, and baseline substance use were associated with baseline attitudes and behaviors as well as changes over time. CONCLUSION: This study offers implications for substance use education opportunities on college campuses. PMID- 22303034 TI - Exploring new frontiers in neuropsychopharmacology: SSRIs for stroke. PMID- 22303035 TI - Effect of marriage on pre-existing psychoses. PMID- 22303037 TI - Sexuality: desire, activity and intimacy in the elderly. AB - BACKGROUND: Sexual function and activity in old age have been inadequately studied world over. It is important to know that aging processes are not confined to persons beyond the age of 60 years; many changes in elderly have their antecedents in the middle age. AIMS: This study sought to determine the patterns of sexual activity and function in individuals over 50 years of age. It also sought to discuss barriers such as chronic illness that may interfere with sexual function. MATERIALS AND METHODS: We conducted a study of subjects above the age of 50 years in various outpatient departments (OPDs) of a teaching municipal hospital in Mumbai, by interviewing 60 individuals who attended the OPDs, after taking their informed consent. Socio-demographic and other information on their sexual function and activities were obtained. Data was analyzed using statistical package for social sciences v15. RESULTS: 72% individuals below 60 were sexually active, while only 57% above 60 were active. Others had become completely abstinent at some time in their lives. Statistical analysis revealed significant gender, health and educational status based differences in the sample. CONCLUSION: Our study showed significant presence of sexual desire, activity and function even after the age of 50 years; a decline by the age of 60 and above was a finding that reflected more in women. Chronic illness did affect sexual function and desire. PMID- 22303036 TI - Serotonin transporter gene polymorphism and psychiatric disorders: is there a link? AB - Though still in infancy, the field of psychiatric genetics holds great potential to contribute to the development of new diagnostic and therapeutic options to treat these disorders. Among a large number of existing neurotransmitter systems, the serotonin system dysfunction has been implicated in many psychiatric disorders and therapeutic efficacy of many drugs is also thought to be based on modulation of serotonin. Serotonin transporter gene polymorphism is one of the most extensively studied polymorphisms in psychiatric behavioral genetics. In this article, we review the status of evidence for association between the serotonin gene polymorphism and some common mental disorders like affective disorders, post-traumatic stress disorder, obsessive-compulsive disorder, suicide, autism, and other anxiety and personality disorders. Going beyond traditional association studies, gene-environment interaction, currently gaining momentum, is also discussed in the review. While the existing information of psychiatric genetics is inadequate for putting into practice genetic testing in the diagnostic work-up of the psychiatric patient, if consistent in future research attempts, such results can be of great help to improve the clinical care of a vast majority of patients suffering from such disorders. PMID- 22303038 TI - Proton magnetic resonance spectroscopy in depression. AB - Magnetic Resonance Spectroscopy (MRS) is a unique technique that can directly assess the concentration of various biochemical metabolites in the brain. Thus, it is used in the study of molecular pathophysiology of different neuropsychiatric disorders, such as, the major depressive disorder and has been an area of active research. We conducted a computer-based literature search using the Pubmed database with 'magnetic resonance spectroscopy', 'MRS', 'depression', and 'major depressive disorder' as the key words, supplemented by a manual search of bibliographic cross-referencing. Studies in depression report abnormalities in the frontal cortex, basal ganglia, hippocampus, anterior cingulate cortex, and the occipital cortex. These abnormalities improve after treatment with selective serotonin reuptake inhibitor, electroconvulsive therapy, and yoga, and thus, are possibly state-dependent. The findings are consistent with other morphometric and clinical studies and support the proposed pathophysiological theory of dysfunction in the neuronal circuits involving the frontal cortex, limbic cortex, and basal ganglia. Spectroscopy also has potential implications in predicting the response to treatment and formulating individualized pharmacotherapy. PMID- 22303039 TI - Are anxiety disorders associated with a more severe form of bipolar disorder in adolescents? AB - BACKGROUND: Anxiety disorders are common among children and adolescents with bipolar disorder. Among adults, anxiety disorder comorbidity is associated with a more severe form of bipolar disorder and a poorer outcome. There is limited data on the effect of comorbid anxiety disorder on bipolar disorder among children and adolescents. AIM: To study the prevalence of anxiety disorders among adolescents with remitted bipolar disorder and examine their association with the course and severity of illness, global functioning, and quality of life. MATERIALS AND METHODS: We evaluated 46 adolescents with DSM IV bipolar disorder (I and II) who were in remission, using the Schedule for Affective Disorders and Schizophrenia for School-Age Children. We measured quality of life using the Pediatric Quality of Life Inventory and global functioning using the Children's Global Assessment Scale, and then compared these parameters between adolescents with and without current anxiety disorders. We also compared the two groups on other indicators of severity such as number of episodes, suicidal ideation, presence of psychotic symptoms, and response to treatment. RESULTS: Among the 46 subjects, the prevalence of current and lifetime anxiety disorders were 28% (n=13) and 41% (n=19), respectively. Compared with others, adolescents with anxiety had more lifetime suicidal ideation, more number of episodes, lower physical, psychosocial, and total subjective quality of life, and lower global functioning. CONCLUSIONS: Among adolescents with bipolar disorder, anxiety disorders are associated with a poorer course, lower quality of life, and global functioning. In these subjects, anxiety disorders should be promptly recognized and treated. PMID- 22303040 TI - Prospective study of duration of untreated psychosis and outcome of never-treated patients with schizophrenia in India. AB - CONTEXT: Longer duration of untreated psychosis (DUP) is known to be associated with poorer outcome of schizophrenia. DUP is also known to be longer in lower- and middle-income countries. Methodologically sound studies that have examined the association of DUP and outcome of schizophrenia in these countries are lacking. AIM: The aim was to evaluate the association between DUP and outcome of never-treated schizophrenia patients. SETTING AND DESIGN: This study was conducted at the National Institute of Mental Health and Neurosciences, Bangalore, using a prospective cohort design. MATERIALS AND METHODS: 119 patients with schizophrenia/schizophreniform disorder diagnosed using the computerized diagnostic interview schedule for DSM-IV (CDIS-IV) were further assessed for DUP with the interview for retrospective assessment of onset of schizophrenia (IRAOS). After a mean (SD) follow-up period of 55.9 (37.2) weeks, the social and occupational functioning and psychopathology of 93 (80.2% of the surviving patients) patients were assessed using the social and occupational functioning scale (SOFS) and the positive and negative syndrome scale (PANSS), by raters blind to the DUP data. Spearman's correlation and Kendall's tau-B test were used to analyze the relationship between DUP and the outcome variables. RESULTS: The mean DUP was 90.2 (median=30.1; SD=121.9) weeks. SOFS and PANSS scores at follow up were statistically significantly associated with DUP, but not with other baseline variables (SOFS: rho=0.22, P=0.03; PANSS: rho=0.23, P=0.03). Among those with the shortest DUP (<16 weeks; n=33), 45.5%, 30.3%, and 24.2% had no impairment, mild-moderate impairment, and severe impairment, respectively. In contrast, 19.4%, 38.7%, and 41.9% of those with the longest DUP (>72 weeks; n=31) had no, mild-moderate, and severe impairment, respectively (Kendall's Tau b=0.194; P=0.025). CONCLUSIONS: The delay in accessing treatment among patients with psychosis is considerable in India, a lower- to middle-income country. Longer DUP is associated with poorer psychopathological and functional outcomes in persons with schizophrenia/schizophreniform disorder. PMID- 22303041 TI - Myths, beliefs and perceptions about mental disorders and health-seeking behavior in Delhi, India. AB - OBJECTIVES: To assess the myths, beliefs and perceptions about mental disorders and health-seeking behavior in general population and medical professionals of India. MATERIALS AND METHODS: A cross-sectional study was carried out with a sample of 436 subjects (360 subjects from urban and rural communities of Delhi and 76 medical professionals working in different organizations in Delhi). A pre tested questionnaire consisting items on perceptions, myths, and beliefs about causes, treatment, and health-seeking behavior for mental disorders was used. The collected data were statistically analyzed using computer software package Epi info. Appropriate tests of significance were applied to detect any significant association. RESULTS: The mental disorders were thought to be because of loss of semen or vaginal secretion (33.9% rural, 8.6% urban, 1.3% professionals), less sexual desire (23.7% rural, 18% urban), excessive masturbation (15.3% rural, 9.8% urban), God's punishment for their past sins (39.6% rural, 20.7% urban, 5.2% professionals), and polluted air (51.5% rural, 11.5% urban, 5.2% professionals). More people (37.7%) living in joint families than in nuclear families (26.5%) believed that sadness and unhappiness cause mental disorders. 34.8% of the rural subjects and 18% of the urban subjects believed that children do not get mental disorders, which means they have conception of adult-oriented mental disorders. 40.2% in rural areas, 33.3% in urban areas, and 7.9% professionals believed that mental illnesses are untreatable. Many believed that psychiatrists are eccentric (46.1% rural, 8.4% urban, 7.9% professionals), tend to know nothing, and do nothing (21.5% rural, 13.7% urban, 3.9% professionals), while 74.4% of rural subjects, 37.1% of urban subjects, and 17.6% professionals did not know that psychiatry is a branch of medicine. More people in rural areas than in urban area thought that keeping fasting or a faith healer can cure them from mental illnesses, whereas 11.8% of medical professionals believed the same. Most of the people reported that they liked to go to someone close who could listen to their problems, when they were sad and anxious. Only 15.6% of urban and 34.4% of the rural population reported that they would like to go to a psychiatrist when they or their family members are suffering from mental illness. CONCLUSION: It can be concluded from this study that the myths and misconceptions are significantly more prevalent in rural areas than in urban areas and among medical professionals, and the people need to be communicated to change their behavior and develop a positive attitude toward mental disorders so that health-seeking behavior can improve. PMID- 22303042 TI - Relationship between religiosity and psychopathology in patients with depression. AB - OBJECTIVE: To compare the psychopathology between depressed patients with low religiosity and those with high religiosity and to correlate the level of religiosity with the psychopathology in the psychiatric clinic of a general hospital in Chandigarh, North India. MATERIALS AND METHODS: Thirty depressed patients with low religiosity and 30 patients with high religiosity were assessed on the Religiosity Scale, Beck Depression Inventory, Hamilton Depression Rating Scale, Beck Hopelessness Scale and Suicidal Intent Questionnaire. RESULTS: In the patients with depression, hopelessness and suicidal intent correlated negatively with the level of religiosity. CONCLUSION: In depressed patients, hopelessness and suicidal intent are inversely related to the level of religiosity. PMID- 22303043 TI - Developing a model for resource room training for slow learners in normal schools. AB - BACKGROUND: A significant number of children with scholastic backwardness in normal schools are slow learners. The aim of the present study was to evaluate the effectiveness of an individualized education program (IEP) for slow learners, modeled on resource room training in normal schools. MATERIALS AND METHODS: 15 children with IQ in the 70-90 range were given individualized education for a period of 4 months. The children were divided into three equal groups and were given individualized training in reading, writing and mathematics for 5 hours a week in two sessions. The academic level of each child was rated before and after the training program by independent assessors. RESULTS: After the training, 87% of children had improvement in either mathematics, reading or writing and 47% had improvement in all the three areas. The overall academic improvement was statistically significant. CONCLUSION: IEP will lead to improvement in academic functioning of children who are slow learners. PMID- 22303044 TI - Augmentation effect of repetitive transcranial magnetic stimulation over the supplementary motor cortex in treatment refractory patients with obsessive compulsive disorder. AB - BACKGROUND: There are only a few effective treatment options currently available for treatment-refractory obsessive compulsive disorder (OCD). The supplementary motor area (SMA) has been reported to play an important role in the pathophysiology of OCD. Functional neuroimaging studies indicate that OCD is associated with increased activity in the SMA, caudate nucleus, and anterior cingulate gyrus. Novel treatment strategies like repetitive transcranial magnetic stimulation (rTMS) have been proposed for OCD refractory to standard treatments. These clinic-based data report on the efficacy of rTMS in medication-resistant OCD. MATERIALS AND METHODS: Twelve right-handed persons with medication-resistant OCD were administered rTMS as an add-on treatment. Stimulation was given at 1 Hz for 10 seconds followed by 15 seconds pause and 100 trains of stimulus over the SMA per session for 5 days in a week. Assessments were done on yale brown obsessive compulsive scale (Y-BOCS) at baseline and at the end of rTMS intervention. RESULTS: The subjects had a mean age of 33.17+/-12.74 years. Mean scores on Y-BOCS were 26.17 at baseline and 17.17 at the end of treatment, reflecting significant improvement. The subjects did not report any significant side effects except one person with known bipolar illness, who developed manic symptoms after the 3(rd) session of the rTMS. CONCLUSIONS: Low-frequency rTMS over the SMA appears a promising treatment strategy as an add-on treatment in treatment-refractory patients of OCD. PMID- 22303045 TI - The ongoing process of amendments in MHA-87 and PWD Act-95 and their implications on mental health care. PMID- 22303046 TI - Maternal mental health in pregnancy and child behavior. AB - Maternal mental health research is a public health priority due to its impact on both maternal and child health. Despite the growing number of empirical studies in this area, particularly from developing countries, there is a paucity of synthetic review articles. Therefore, attempting to synthesize the existing literature in this area seems relevant to appraise the readers of the field's progress and to infer directions for future research. The present review aims to provide an overview of the literature on maternal mental health and its association with birth outcomes and child behavior. Specifically, the literature on mental health during pregnancy and in the postpartum period and its influence on birth outcomes and child behavior have been reviewed. Further, a conceptual and methodological evaluation of the existing literature has been provided to identify gaps in the literature and to suggest directions for future research. PMID- 22303047 TI - How to read a research paper: Reading between and beyond the lines. AB - BACKGROUND: Despite peer review, publications in scientific journals are not always well written, sometimes contain errors, and often exhibit deliberate or unintended biases. It is necessary to learn how to identify such limitations. It is also necessary to learn how to read between and beyond the lines of papers no matter how well written they are and no matter how highly ranked the journal is. MATERIALS AND METHODS: This paper critically examines an important article in a leading journal with a view to help the reader learn how to place the findings of a study in perspective, understand its limitations, and glean information beyond that actually presented and discussed in the text. RESULTS: Several issues are examined; these relate to case-control research designs, confounding, propensity matching, absolute risk, confidence intervals, interpretation of findings, real world relevance, ecological validity, and definition of a cause-effect relationship. CONCLUSIONS: The issues examined in this paper reflect common themes in research, and a reader aware of these themes will more easily identify them in his future readings. PMID- 22303048 TI - Acute disseminated encephalomyelitis presenting as depressive episode. AB - A 9-year-old girl presented to the Child Guidance Clinic with clinical features suggestive of depressive episode of 1 week duration. There was history of short febrile illness 3 weeks prior to the onset of the depressive symptoms. MRI scan of brain showed features of acute disseminated encephalomyelitis. PMID- 22303049 TI - Negative symptoms presenting as neuropsychiatric manifestation of vitamin B12 deficiency. AB - Long lists of psychiatric illness or symptoms have been documented to be caused by vitamin B12 deficiency. We describe an atypical case of a young adult who presented with predominant negative symptoms followed by neurological symptoms consistent with vitamin B12 deficiency. The symptoms showed complete remission after vitamin B12 supplementation. The uniqueness of this case is that vitamin B12 deficiency presented with predominant negative symptoms without other psychotic and manic symptoms, which has not been reported previously. PMID- 22303050 TI - Serotonin syndrome while switching antidepressants. PMID- 22303051 TI - Folie 'a famillie in a family multiply affected with schizophrenia. PMID- 22303052 TI - Indianizing psychiatry. PMID- 22303053 TI - Ethics in clinical research: the Indian perspective. AB - Ethics in clinical research focuses largely on identifying and implementing the acceptable conditions for exposure of some individuals to risks and burdens for the benefit of society at large. Ethical guidelines for clinical research were formulated only after discovery of inhumane behaviour with participants during research experiments. The Nuremberg Code was the first international code laying ethical principles for clinical research. With increasing research all over, World Health Organization formulated guidelines in the form of Declaration of Helsinki in 1964. The US laid down its guidelines for ethical principles in the Belmont Report after discovery of the Tuskegee's Syphilis study. The Indian Council of Medical Research has laid down the 'Ethical Guidelines for Biomedical Research on Human Subjects' in the year 2000 which were revised in 2006. It gives twelve general principles to be followed by all biomedical researchers working in the country. The Ethics Committee stands as the bridge between the researcher and the ethical guidelines of the country. The basic responsibility of the Ethics Committee is to ensure an independent, competent and timely review of all ethical aspects of the project proposals received in order to safeguard the dignity, rights, safety and well-being of all actual or potential research participants. A well-documented informed consent process is the hallmark of any ethical research work. Informed consent respects individual's autonomy, to participate or not to participate in research. Concepts of vulnerable populations, therapeutic misconception and post trial access hold special importance in ethical conduct of research, especially in developing countries like India, where most of the research participants are uneducated and economically backward. PMID- 22303054 TI - Increased in vitro Cell Proliferation by Chitosan/pGM-CSF Complexes. AB - Granulocyte macrophage colony stimulating factor, a potent hematopoietic cytokine, has been shown to stimulate production of white blood cells following chemotherapy. Therefore, the granulocyte macrophage colony stimulating factor gene is a potential candidate for the treatment of different pathological conditions. The purpose of this study is to investigate the suitability of chitosan as carrier for pORF-hGMCSF plasmid encoding granulocyte macrophage colony stimulating factor gene and also to study the effect of complexes on protein production and cell proliferation. Chitosan/pGM-CSF complexes were prepared using different (+/-) ratios (from 0.01/1 to 5/1). Complex formation was checked with agarose gel electrophoresis. The size and zeta potential values were measured. Enzyme and serum stability of complexes were studied. In vitro transfection properties of complexes were studied in HeLa cells. According to agarose gel electrophoresis, full complexation was obtained at 0.1/1 and higher chitosan/pGM-CSF ratios. Complexes having about 132 nm size and +13.7 mV zeta potential value were obtained. Chitosan complexes protected plasmid against enzymatic and serum effects. The gene expression-dependent cell proliferation after transfection of chitosan/pGM-CSF complexes at 72 h was markedly increased in comparision with the level of control group. These results indicate that the effect of chitosan/pGM-CSF complexes on cell proliferation was changed with N/P ratio and time-dependently. For GM-CSF therapy, chitosan/pGM-CSF complexes may be used as alternative to conventional protein treatments. Chitosan may be a good carrier for pORF-hGMCSF. Further, in vivo study is ongoing. PMID- 22303055 TI - Antihyperglycemic and antihyperlipidemic activity of plectranthus amboinicus on normal and alloxan-induced diabetic rats. AB - The present study was undertaken to investigate the antihyperglycemic and antihyperlipidemic effects of ethanol extract of Plectranthus amboinicus in normal and alloxan-induced diabetic rats. Diabetes was induced in Wistar rats by single intraperitoneal administration of alloxan monohydrate (150 mg/kg). Normal as well as diabetic rats were divided into groups (n=6) receiving different treatments. Graded doses (200 mg/kg and 400 mg/kg) of ethanol extract of Plectranthus amboinicus were studied in both normal and alloxan-induced diabetic rats for a period of 15 days. Glibenclamide (600 MUg/kg) was used as a reference drug. Oral administration with graded doses of ethanol extract of Plectranthus amboinicus exhibited hypoglycemic effect in normal rats and significantly reduced the peak glucose levels after 120 min of glucose loading. In alloxan-induced diabetic rats, the daily oral treatment with ethanol extract of Plectranthus amboinicus showed a significant reduction in blood glucose. Besides, administration of ethanol extract of Plectranthus amboinicus for 15 days significantly decreased serum contents of total cholesterol, triglycerides whereas HDL-cholesterol, total proteins and calcium were effectively increased. Furthermore, effect of ethanol extract of Plectranthus amboinicus showed profound elevation of serum amylase and reduction of serum lipase. Histology examination showed ethanol extract of Plectranthus amboinicus exhibited almost normalization of damaged pancreatic architecture in rats with diabetes mellitus. Studies clearly demonstrated that ethanol extract of Plectranthus amboinicus leaves possesses hypoglycemic and antihyperlipidemic effects mediated through the restoration of the functions of pancreatic tissues and insulinotropic effect. PMID- 22303056 TI - Estimation of phytochemical content and antioxidant activity of some selected traditional Indian medicinal plants. AB - The powder samples and methanol extract of 11 medicinal plants were subjected to analysis of proximate composition and measurement of antioxidant activity. Different parameters studied include phenolic contents, moisture, ash, crude fiber, fats and waxes. The assays employed were ferric reducing antioxidant power, trolox equivalent antioxidant capacity and scavenging effect on the 1,1 diphenyl-2-picrylhydrazyl free radical. Results obtained indicate that the antioxidant potential varied significantly from plant to plant. The total phenolic contents were determined spectrophotometrically using Folin-Ciocalteu reagent. Significant correlation is observed between ferric reducing antioxidant power and phenolic contents (R(2) = 0.96). These findings show that the polyphenolic constituents in the extracts are responsible for free radical scavenging capacity. PMID- 22303057 TI - Exacerbation of alcohol-induced oxidative stress in rats by polyunsaturated Fatty acids and iron load. AB - The hypothesis that excessive intake of vegetable oil containing polyunsaturated fatty acids and iron load precipitate alcohol-induced liver damage was investigated in a rat model. In order to elucidate the mechanism underlying this synergism, the serum levels of iron, total protein, serum glutamate pyruvate transaminase, liver thiobarbituric acid reactive substances, and activities of antioxidant enzymes superoxide dismutase, catalase in liver of rats treated with alcohol, polyunsaturated fatty acids and iron per se and in combination were examined. Alcohol was fed to the rats at a level of 10-30% (blood alcohol was maintained between 150-350 mg/dl by using head space gas chromatography), polyunsaturated fatty acids at a level of 15% of diet and carbonyl iron 1.5-2% of diet per se and in combination to different groups for 30 days. Hepatotoxicity was assessed by measuring serum glutamate pyruvate transaminase, which was elevated and serum total protein, which was decreased significantly in rats fed with a combination of alcohol, polyunsaturated fatty acids and iron. It was also associated with increased lipid peroxidation and disruption of antioxidant defense in combination fed rats as compared to rats fed with alcohol or polyunsaturated fatty acids or iron. The present study revealed significant exacerbation of the alcohol-induced oxidative stress in presence of polyunsaturated fatty acids and iron. PMID- 22303058 TI - Benzoxazinones as Human Peroxisome Proliferator Activated Receptor Gamma (PPARgamma) Agonists: A Docking Study Using Glide. AB - The purpose of the present study is to undertake a docking study of some benzoxazinone derivatives on human peroxisome proliferator activated receptor co crystallized with an alpha-aryloxyphenylacetic acid agonist using Glide 4.5. The QikProp program was used to obtain the absorption, distribution, metabolism and excretion properties of the analogues. The intermolecular hydrogen bonding interaction of the best-fit ligands were found to be associated with Tyr473, Ser289, Hie 449, Hip 323, Ser 342 and Gly 284 amino acid residue at the receptor active site. Among all the observed interaction with similar binding pattern, the presence of methyl carboxypentyl side chain (Lig. No. 21) showed additional interaction with Ser 342 and the affinity was increased by carboxyl oxygen (as hydrogen bond acceptor) with a best Glide score of -14.54 as compared to the co crystallized aryloxyphenyl acetic acid which achieved a glide score of -12.50. PMID- 22303059 TI - 2D QSAR Studies of Several Potent Aminopyridine, Anilinopyrimidine and Pyridine Carboxamide-based JNK Inhibitors. AB - The c-Jan N-terminal kinases are members of the mitogen activated protein kinase family of signaling proteins. Amino pyridine based compounds, 4-anilino pyrimidine derivatives, and 2-pyridine carboxamide derivatives have been identified as potent JNK inhibitors with good cellular activity. In this study we calculated molecular topological and quantum chemical descriptors of 15 training compounds and three quantitative structure activity relationships models have been constructed. The significance of three models is judged on the basis of correlation, Fischer F test and quality factor (Q). This study is helpful for screening potent inhibitors of protein kinases. PMID- 22303060 TI - Synthesis and biological evaluation of some novel 3,4-disubstituted isocoumarins. AB - In this paper we report the synthesis of a new family of 4-alkyl isocoumarin derivatives having bromo carbonyl and amino carbonyl group at 3(rd) position of the heterocyclic ring. Synthesis, spectral analysis and bioactivity of new isocoumarin derivatives are discussed in this paper. Some of the synthesized compounds displayed comparable antibacterial activity and some of the new compounds showed an interesting inhibitory effect on the growth of four pathogen fungi involved in plant diseases. A fair number of compounds were found to have good analgesic property on comparing with standard drug analgin. PMID- 22303061 TI - Mixed hydrotropy: novel science of solubility enhancement. AB - Conventional furosemide tablets are practically insoluble in water, have slow onset of action (45-60 min) and poor bioavailability (39-53%), and therefore cannot be given in emergency clinical situations like hypertension or pulmonary edema. So purpose of research was to provide a fast dissolving oral dosage form of furosemide, which can provide quick onset of action by using concept of mixed hydrotropy. Initially solubility of furosemide was determined individually in 4 hydrotropic agents namely urea, sodium acetate, sodium benzoate, sodium citrate at concentration of 10, 20, 30 and 40% w/v solutions using purified water as solvent. Highest solubility was obtained in 40% sodium benzoate solution. Then different combinations of 2, 3 and 4 hydrotropic agents in different ratios were used to determine solubility, so that total concentration of hydrotropic agents was always 40%. Highest solubility was obtained in solution of urea+sodium benzoate+sodium citrate at optimum ratio of 15:20:5. This optimized combination was utilized in preparing solid dispersions by common solvent technique using distilled water as solvent. Solid dispersions were evaluated for flow properties, XRD, DSC, SEM and were also compressed to form tablets. Dissolution studies of conventional and prepared tablets were done using USP Type II apparatus. It was concluded that the concept of mixed hydrotropic solid dispersion is novel, safe and cost-effective technique for enhancing bioavailability of poorly water soluble drugs by dissolving drug in nonionized form. The magical enhancement in solubility of furosemide is clear indication of its potential to be used in future for other poorly water-soluble drugs in which low bioavailability is major concern. PMID- 22303062 TI - Design and optimization of a novel method for extraction of genistein. AB - Genistein, an isoflavone, has been demonstrated to promote the health of human beings by reducing the incidence of specific chronic diseases, namely, cancer and atherosclerosis. The present investigation explores a novel method of extraction of genistein from soy source which consists of a bioconversion reaction using fermentation by microorganism namely Streptomyces roseolus NRRL B-5424. In situ bioconversion of genistein glycoside to aglycone was carried out by the microbe. Such methodology has not been reported hitherto. Optimization of upstream and downstream parameters was done for maximum extraction of genistein. Genistein was isolated in a powder form by column chromatography and preparative thin layer chromatography and was characterized using massspectrometry, nuclear magnetic resonance and infrared spectroscopy and its purity determined using high performance liquid chromatography. Genistein was extracted with 91.04% purity and extraction efficiency was 67.01%. PMID- 22303063 TI - Influence of proton pump inhibitors on dexamethasone-induced gastric mucosal damage in rats. AB - The present study was designed to compare the curative role of proton pump inhibitors, omeprazole, rabeprazole and lansoprazole against dexamethasone induced ulcer model. Dexamethasone (5 mg/kg/day) was used as an ulcerogen. Dexamethasone suspended in 1% CMC in water was given orally to all rats. Omeprazole (20 mg/kg), rabeprazole (20 mg/kg), and lansoprazole (20 mg/kg) were administered by oral route 30 minutes prior to dexamethasone for ulcer protective studies, gastric secretion and mucosal studies. Effects of proton pump inhibitors were determined by the evaluation of various biochemical parameters such as estimation of myeloperoxidase, cortisol, alkaline phosphatase, malondialdehyde, endogenous anti-oxidants like superoxide dismutase, catalase and reduced glutathione. In dexamethasone induced ulcer model, omeprazole showed significant decrease in malondialdehyde, myeloperoxidase, alkaline phosphatase level and increase in superoxide dismutase, catalase and reduced glutathione level as compared to rabeprazole and lansoprazole. Omeprazole showed significant reduction in cortisol content where as rabeprazole and lansoprazole did not show significant changes as compared to control. The result indicates that omeprazole is the most effective and selective proton pump inhibitor in dexamethasone induced ulcer model as compared to rabeprazole and lansoprazole. PMID- 22303064 TI - Microwave-assisted Heterocyclic Dicarboxylic Acids as Potential Antifungal and Antibacterial Drugs. AB - A series of new dicarboxylic acid derivatives of 1,3,4-thiadiazines, 1,4 benzopiperizines, 1,4-thiazines, 1,3-thiazoles, 1,3-oxazoles and 1,3-imidazoles have been synthesized in 80-87% yield by the environmentally benign microwave induced technique involving the cyclocondensation of 2,3-dibromosuccinic acid with 2-aminothiophenol, o-phenylene diamine, 1,2,4-triazole, amidinothiocarbamide, amidinocarbamide and guanidine hydrochloride. The structures of all newly synthesized compounds have been established on the basis of analytical and spectral data. Evaluation of antibacterial and antifungal activity showed that almost all compounds exhibited better results than reference drugs thus they could be promising candidates for novel drugs. PMID- 22303065 TI - Formulation and evaluation of a sustained-release tablets of metformin hydrochloride using hydrophilic synthetic and hydrophobic natural polymers. AB - Metformin hydrochloride has relatively short plasma half-life, low absolute bioavailability. The need for the administration two to three times a day when larger doses are required can decrease patient compliance. Sustained release formulation that would maintain plasma level for 8-12 h might be sufficient for daily dosing of metformin. Sustained release products are needed for metformin to prolong its duration of action and to improve patient compliances. The overall objective of this study was to develop an oral sustained release metformin hydrochloride tablet by using hydrophilic Eudragit RSPO alone or its combination with hydrophobic natural polymers Gum copal and gum damar as rate controlling factor. The tablets were prepared by wet granulation method. The in vitro dissolution study was carried out using USP 22 apparatus I, paddle method and the data was analysed using zero order, first order, Higuchi, Korsmeyer and Hixson Crowell equations. The drug release study revealed that Eudragit RSPO alone was unable to sustain the drug release. Combining Eudragit with gum Copal and gum Damar sustained the drug release for more than 12 h. Kinetic modeling of in vitro dissolution profiles revealed the drug release mechanism ranges from diffusion controlled or Fickian transport to anomalous type or non-Fickian transport. Fitting the in vitro drug release data to Korsmeyer equation indicated that diffusion along with erosion could be the mechanism of drug release. PMID- 22303066 TI - Estimation of Embelin in Embelia tsjeriam-cottam Fruits by HPLC to Standardize Harvesting Time. AB - Embelin (2,5-dihydroxy-3-undecyl-2,5-cyclohexadiene-1,4-benzoquinone) is a phenolic compound found in the fruits of Embelia tsjeriam-cottam and is responsible for the medicinal properties of the plant Thus the fruits are harvested at a large scale before maturity leading to depletion of population. Since the chemical constituents of medicinal plants are directly associated with the harvesting time, a study was conducted in different forest areas of Chhattisgarh, India, to standardize the harvesting time of Baividang fruits on the basis of their embelin content during 2005-08. The embelin content was determined by RP-HPLC and varied from 1.09 to 5.21% (w/w). The immature fruits collected in October contain an average of 1.67% embelin whereas mature fruits collected in December on an average contain 4.64% embelin. On the basis of our findings it can be concluded that fruits should be harvested after attaining maturity to get better quality produce and also to maintain the sustainability of plant. PMID- 22303067 TI - Analytical Method for the Simultaneous Estimation of Hydrochlorothiazide and Metoprolol Tartrate using RP HPLC. AB - The present study deals with the estimation by RP-HPLC of two different drug components hydrochlorothiazide and metoprolol tartrate present in a tablet formulation. It is a simple, fast, precise and accurate high performance liquid chromatographic method. It is performed using phosphate buffer along with methanol as mobile phase, in the proportion of 60:40. The separation is done on a C(18) column and it is estimated at a lambda(max) of 226 nm with a flow of 1 ml/min. The detection limits range from a 0.013 to 0.075 mg/ml for hydrochlorothiazide and 0.10 to 0.60 mg/ml for metoprolol tartrate, respectively. The specificity for interference of any peak with main peak of interest is checked. A scan of the individual drug was taken for assuring the lambda(max). The system suitability by precision is also checked to ensure the analytical method. The method was found to be accurate and precise for estimation of the two drugs simultaneously. PMID- 22303068 TI - Antimicrobial Screening of Actinobacteria using a Modified Cross-Streak Method. AB - Out of the 30 actinobacterial cultures screened for antimicrobial activity, 28 cultures were found to produce active products against various pathogenic microorganisms such as Gram-negative, Gram-positive bacteria and yeast, using a modified cross streak method. The modified method helped in easy quantification of results and also in ruling out probable mutual antibiosis. The actinobacterial strains that showed the ability to produce antimicrobial compounds belonged to Streptomyces (53%), Micromonospora (13%) and Actinomadura (10%) genera. Streptomyces sp. strain MMA-5 showed the highest multispecific antibiosis efficiency score value. Broad antibiotic spectrum activity was exhibited by Streptomyces sp. strain MMA-2 and Micromonospora sp. strain MMA-8. The multidrug resistant human pathogenic yeast strain Candida albicans was inhibited by 18 actinobacterial strains. PMID- 22303069 TI - Diuretic activity of leaves of garcinia cambogia in rats. AB - The present study was undertaken to establish the diuretic activity of ethanol and aqueous extract of dried leaves of Garcinia cambogia in rats. Aqueous and ethanol extracts of leaves were administered to experimental rats orally at doses of 100 and 200 mg/kg and compared with furosemide (20 mg/kg, intraperitoneally) as the standard. The parameters measured for diuretic activity were total urine volume, urine concentration electrolytes such as sodium, potassium and chloride have been evaluated . The rats treated with ethanol extract of Garcinia cambogia and aqueous extract of Garcinia cambogia in a dose of 100 and 200 mg/kg showed higher urine output when compared to the respective control. Both ethanol and aqueous extracts have showed a significant dose-dependent increase in the excretion of electrolytes when compared to the control group. PMID- 22303070 TI - Triterpenoids from Schleichera oleosa of Darjeeling Foothills and Their Antimicrobial Activity. AB - Two triterpenoids, taraxerone and tricadenic acid A were isolated from the methanol extract of the outer bark of Schleichera oleosa available in Darjeeling foothills. A preliminary study on their antimicrobial activities was also performed against some fungal and bacterial species. The structure of these compounds was determined by means of chemical characterisation and IR, NMR spectral data. PMID- 22303071 TI - Seasonal Variation in Essential Oil Content and Composition of Thyme, Thymus serpyllum L. Cultivated in Uttarakhand Hills. AB - Thymus serpyllum L. grown in Kumaon region of Western Himalaya was investigated for essential oil content and composition in different seasons. The oils of fresh samples were obtained by hydrodistillation. The yield of essential oil (% v/w) during different seasons varied from 0.07 to 0.28% with the highest in summer season, at vegetative stage. The oils were analyzed by GC and GC-MS. Major components of all the samples were thymol (19.4-60.1%), gamma-terpinene (0.3 13.8%) and p-cymene (3.5-10.4%). The results clearly indicated that season has significant effect on quality and quantity of thyme oil. PMID- 22303072 TI - Immunomodulatory Potential of Methanol Extract of Aegle marmelos in Animals. AB - The aim of the current research was to evaluate the immunomodulatory potential of methanol extract of Aegle marmelos in an experimental animal model of cellular and humoral immunity. Administration of methanol extract of Aegle marmelos (500 and 1000 mg/kg, p.o.) and Ocimum sanctum (100 mg/kg, p.o.), produced significant increase in adhesion of neutrophils and an increase in phagocytic index in carbon clearance assay. Both doses of Aegle marmelos prevented the mortality induced by bovine Pasteurella multocida in mice. Moreover, all treated groups demonstrated significant elevation in circulating antibody titre in the indirect haemagglunation test. From the above results, it can be concluded that methanol extract of Aegle marmelos possess immunomodulatory potential by stimulating cellular and humoral immune mechanisms. However, low dose of methanol extract of Aegle marmelos was more effective for augmenting cellular immunity, whereas, high dose was more inclined towards humoral immunity. PMID- 22303073 TI - Simultaneous determination of withanolide a and bacoside a in spansules by high performance thin-layer chromatography. AB - The objective of this work was to develop and validate a simple, rapid, precise, and accurate high performance thin layer chromatography method for simultaneous determination of withanolide A and bacoside A in combined dosage form. The stationary phase used was silica gel G60F(254). The mobile phase used was mixture of ethyl acetate: methanol: toluene: water (4:1:1:0.5 v/v/v/v). The detection of spots was carried out at 320 nm using absorbance reflectance mode. The method was validated in terms of linearity, accuracy, precision and specificity. The calibration curve was found to be linear between 200 to 800 ng/spot for withanolide A and 50 to 350 ng/spot for bacoside A. The limit of detection and limit of quantification for the withanolide A were found to be 3.05 and 10.06 ng/spot, respectively and for bacoside A 8.3 and 27.39 ng/spot, respectively. The proposed method can be successfully used to determine the drug content of marketed formulation. PMID- 22303074 TI - In vitro Dissolution Studies on Solid Dispersions of Mefenamic Acid. AB - Solid dispersions of mefanamic acid with a water-soluble polymer polyvinyl pyrrolidine and a super disintegrant, primojel were prepared by common solvent and solvent evaporation methods employing methanol as the solvent. The dissolution rate and dissolution efficiency of the prepared solid dispersions were evaluated in comparison to the corresponding pure drug. Solid dispersions of mefenamic acid showed a marked enhancement in dissolution rate and dissolution efficiency. At 1:4 ratio of mefenamic acid-primojel a 2.61 fold increase in the dissolution rate of mefenamic acid was observed with solid dispersion. The solid dispersions in combined carriers gave much higher rates of dissolution than super disintegrants alone. Mefanamic acid-primojel-polyvinyl pyrrolidine (1:3.2:0.8) solid dispersion gave a 4.11 fold increase in the dissolution rate of mefenamic acid. Super disintegrants alone or in combination with polyvinyl pyrrolidine could be used to enhance the dissolution rate of mefenamic acid. PMID- 22303075 TI - In vitro Evaluation of Antifungal Activity of the Seed Extract of Embelia Ribes. AB - Antifungal activity of Embelia ribes was evaluated on eight different fungal species by employing various concentrations of seed extract (0.5-2.0 mg). All the concentrations of seed extract inhibited the fungal growth, whereas maximum activity was observed at 2.0 mg concentration of seed extract. Among different doses, the diameter of inhibition zones ranged from 9 to 18 mm in various fungal species and increased with the increase in the concentration of test solution. Among all the fungi, high inhibition zones were observed in Colletotricum crassipes (18 mm). This was followed by Cladosporium (17.5 mm), Armillaria mellea (17 mm), Colletotricum capsici (17 mm), Aspergillus niger (16.5 mm), Rhizopus oryzae (16.5 mm), respectively. Aspergillus terreus and Candida albicans showed less inhibition zones (15.5 and 16.0 mm) compared to other organisms. The present study clearly demonstrated the antifungal properties of Embelia ribes. PMID- 22303076 TI - Protective Effect of Hydroalcoholic Root Extract of Rubia cordifolia in Indomethacin-Induced Enterocolitis in Rats. AB - This study was undertaken to investigate the possible effect of hydroalcoholic root extract of Rubia cordifolia against indomethacin-induced enterocolitis in rats. Male Wistar rats received vehicle or hydroalcoholic root extract of Rubia cordifolia (300 and 600 mg/kg) for 11 consecutive days. Enterocolitis was induced by subcutaneous administration of indomethacin (7.5 mg/kg) on 8(th) and 9(th) day. The colonic mucosal injury was assessed by macroscopic scoring and histopathological examination. Furthermore, the serum lactate dehydrogenase activity was estimated. Indomethacin treatment to rats produced acute intestinal inflammation, manifested by a thickening of the bowel wall, mesenteric haemorrhage, mesentery adhesion and multiple mucosal ulcers of small intestine and colon. Treatment with hydroalcoholic root extract of Rubia cordifolia revealed less damage to intestinal tissue and decreased serum lactate dehydrogenase activity which was elevated by induction of colitis. The present data suggests protective effect of Rubia cordifolia in indomethacin-induced enterocolitis and may be beneficial in patients with inflammatory bowel diseases. PMID- 22303077 TI - Spin Chemistry: Coherent Spin Dynamics Rules Chemical Reactions. PMID- 22303078 TI - N Photo-CIDNP MAS NMR To Reveal Functional Heterogeneity in Electron Donor of Different Plant Organisms. AB - In plants and cyanobacteria, two light-driven electron pumps, photosystems I and II (PSI, PSII), facilitate electron transfer from water to carbon dioxide with quantum efficiency close to unity. While similar in structure and function, the reaction centers of PSI and PSII operate at widely different potentials with PSI being the strongest reducing agent known in living nature. Photochemically induced dynamic nuclear polarization (photo-CIDNP) in magic-angle spinning (MAS) nuclear magnetic resonance (NMR) measurements provides direct excess to the heart of large photosynthetic complexes (A. Diller, Alia, E. Roy, P. Gast, H.J. van Gorkom, J. Zaanen, H.J.M. de Groot, C. Glaubitz, J. Matysik, Photosynth. Res. 84, 303-308, 2005; Alia, E. Roy, P. Gast, H.J. van Gorkom, H.J.M. de Groot, G. Jeschke, J. Matysik, J. Am. Chem. Soc. 126, 12819-12826, 2004). By combining the dramatic signal increase obtained from the solid-state photo-CIDNP effect with (15)N isotope labeling of PSI, we were able to map the electron spin density in the active cofactors of PSI and study primary charge separation at atomic level. We compare data obtained from two different PSI proteins, one from spinach (Spinacia oleracea) and other from the aquatic plant duckweed (Spirodella oligorrhiza). Results demonstrate a large flexibility of the PSI in terms of its electronic architecture while their electronic ground states are strictly conserved. PMID- 22303079 TI - Exploring Chromophore-Binding Pocket: High-Resolution Solid-State H-C Interfacial Correlation NMR Spectra with Windowed PMLG Scheme. AB - High-resolution two-dimensional (2D) (1)H-(13)C heteronuclear correlation spectra are recorded for selective observation of interfacial 3-5.5 A contacts of the uniformly (13)C-labeled phycocyanobilin (PCB) chromophore with its unlabeled binding pocket. The experiment is based on a medium- and long-distance heteronuclear correlation (MELODI-HETCOR) method. For improving (1)H spectral resolution, a windowed phase-modulated Lee-Goldburg (wPMLG) decoupling scheme is applied during the t(1) evolution period. Our approach allows for identification of chromophore-protein interactions, in particular for elucidation of the hydrogen-bonding networks and charge distributions within the chromophore-binding pocket. The resulting pulse sequence is tested on the cyanobacterial (Cph1) phytochrome sensory module (residues 1-514, Cph1Delta2) containing uniformly (13)C- and (15)N-labeled PCB chromophore (u-[(13)C,(15)N]-PCB-Cph1Delta2) at 17.6 T. PMID- 22303080 TI - Single incision laparoscopic cholecystectomy: A review on the complications. AB - BACKGROUND: The aim of this study was to establish the incidence of postoperative complications after single incision laparoscopic cholecystectomy. MATERIALS AND METHODS: A literature search was performed using the PubMed database. Search terms included single incision laparoscopic cholecystectomy, single port cholecystectomy, minimal invasive laparoscopic cholecystectomy, nearly scarless cholecystectomy and complications. RESULTS: A total of 38 articles meeting the selection criteria were reviewed. A total of 1180 patients were selected to undergo single incision laparoscopic cholecystectomy. Introduction of extra ports was necessary in 4% of the patients. Conversion to open cholecystectomy was required in 0.4% of the patients. Laparoscopic cholangiography was attempted in 4% of the patients. The incidence of major complications requiring surgical intervention or ERCP with stenting was 1.7%. The mortality rate was zero. CONCLUSION: Although the number of complications after single incision laparoscopic cholecystectomy seems favourable, it is too early to conclude that single incision laparoscopic cholecystectomy is a safe procedure. Large randomised controlled trials will be necessary to further establish its safety. PMID- 22303081 TI - The "BASE-FIRST" technique in laparoscopic appendectomy. AB - BACKGROUND: Appendicitis is the most common cause of acute abdomen, and appendectomy is the most frequent surgical procedure performed in the world. In recent times, laparoscopic appendectomy has been gaining increasing consensus, although comparison with traditional open surgery is still debated. Recent reports seem to agree in recognizing laparoscopy as the favourable approach in cases of non-complicated appendicitis, in women and in obese patients. The use of a linear stapler to close the appendiceal stump also seems to guarantee a dramatic decrease of complications and this observation could be the rationale for considering the laparoscopic approach to also be safe in complicated appendicitis. In these cases, dissection of the mesoappendix and isolation of the viscum could be very difficult and could cause complications. By proposing this technique using a laparoscopic approach, we try to permit a simple and safe section of the appendix leaving the detachment from vessels and from the neighbourhood to a second moment. MATERIALS AND METHODS: We report our initial experience including the first 50 cases and proposing our personal technique of laparoscopic appendectomy. RESULTS AND CONCLUSION: We recorded only one intraoperative haemorrhage, one bladder perforation due to trocar insertion and no conversion. Our goal is to standardize and simplify the laparoscopic approach in order to give any surgeon, even non-expert ones, a simple way to remove the viscum especially in complicated pictures. PMID- 22303082 TI - The barrier-free trocar technique in three laparoscopic standard procedures. AB - BACKGROUND: Numerous technical and surgical innovations took place in laparoscopic surgery in the recent past. It is debatable whether single-access surgery or natural orifice surgery (NOS) will establish for several standard procedures. Most of the NOS-procedures are controversial and single-access surgery still has to prove its equality in controlled trials. In the intention to reduce the ingress incisons and to facilitate instrumentation, we decided to test the barrier-free AirSeal((r))-trocar in clinical practice. MATERIALS AND METHODS: Laparoscopically we performed a cholecystectomy, gastric wedge-resection and a fundoplication using the barrier-free AirSeal((r)) 12-mm-trocar. This trocar works without any mechanical barrier so that via this trocar the use of two instruments is possible. RESULTS: All three operations were successful. CONCLUSION: Laparoscopic standard procedures are feasible using this barrier-free trocar without a higher degree of difficulty. Because of the facilitated instrumentation, it is possible to work more efficiently and to maintain the focus on the surgical field. PMID- 22303083 TI - Laparoscopic resection of extra-adrenal pheochromocytoma in paediatric age. AB - Today, in the era of minimally invasive surgery, paediatric laparoscopy has become widely popular. Extra-adrenal pheochromocytoma is a very rare entity, especially in the paediatric age group and utility of the laparoscopic approach is not established in this population. Early diagnosis and surgical excision are integral part of treatment of childhood pheochromocytoma. We present a case study of a child with hormonally active extra-adrenal pheochromocytoma that was resected laparoscopically. Laparoscopic approach provides excellent exposure with magnification and allows proper identification of the tumour and its relation to surrounding structures; complete resection of tumour was achieved with adequate vascular control. With our initial experience, we suggest laparoscopic resection is an appropriate and feasible tool in such cases. PMID- 22303084 TI - Laparoscopic release of median arcuate ligament. AB - Median arcuate ligament (MAL) syndrome, also known as the celiac axis compression syndrome, is rare. It is a diagnosis of exclusion, characterised by the clinical triad of postprandial abdominal pain, weight loss and vomiting. Computed tomographic angiography is the gold standard for making the diagnosis of MAL and colour Doppler is essential to confirm the diagnosis. The classic management involves the surgical division of the MAL fibres. We report successful management of two patients diagnosed as MAL syndrome and treated by laparoscopic release of the MAL. PMID- 22303085 TI - Successful management of pleural lipoma by video-assisted thoracoscopic surgery. AB - Pleural lipoma is an extremely rare clinical entity. Symptomatic pleural lipoma is rarer. We report a case of symptomatic pleural lipoma which was successfully managed by video-assisted thoracoscopic surgery (VATS). A brief review of relevant literature has been included in the article. PMID- 22303086 TI - Laparoscopic right radical hemicolectomy. AB - Laparoscopic right hemicolectomy is an advanced cancer surgery in today's era. With increasing experience, we have described novel technique for this procedure. To prevent falling down of the colon in the operative field and to have early control on vessels, we go from medial to lateral approach. PMID- 22303087 TI - Boerhaave syndrome. PMID- 22303088 TI - Imaging in ureteric stones. PMID- 22303089 TI - High-performance liquid chromatography analysis of plant saponins: An update 2005 2010. AB - Saponins are widely distributed in plant kingdom. In view of their wide range of biological activities and occurrence as complex mixtures, saponins have been purified and separated by high-performance liquid chromatography using reverse phase columns at lower wavelength. Mostly, saponins are not detected by ultraviolet detector due to lack of chromophores. Electrospray ionization mass spectrometry, diode array detector , evaporative light scattering detection, and charged aerosols have been used for overcoming the detection problem of saponins. PMID- 22303090 TI - Wesley College Ignites Potential with Undergraduate Research Program. PMID- 22303091 TI - Synthesis and Crystal Structure of the Azoxydichinyl Helicene, Pyrido[3,2 f]quinolino[6,5-c]cinnoline 5-Oxide Monohydrate. AB - The helicene, pyrido[3,2-f]quinolino[6,5-c]cinnoline 5-oxide, was prepared by treatment of 6-hydroxylaminoquinoline with xanthine oxidase or treatment of 6 nitroquinoline with glucose in 30% NaOH and the product characterized using NMR, high resolution mass spectrometry, and X-ray crystallography. The hydrogens on carbons 7 and 12 of the terminal aromatic rings are separated by 2.495 A creating an angle of 25.0 degrees between the planes of the two quinoline ring systems. In the crystal, water molecules serve to link the helicenes into a one dimensional chain structure forming a hydrogen bonded bridge between N2 of one molecule and N4 of another. The molecule (C(18)H(10)N(4)O*H(2)O) crystallized in the monoclinic P2(1)/n space group. Unit cell parameters for pyrido[3,2 f]quinolino[6,5-c]cinnoline 5-oxide monohydrate: a = 7.0829(12), b = 18.559(3), c = 11.0985(19) A, beta = 107.736(2) degrees , and Z = 4. PMID- 22303092 TI - On some surface structures of potential taxonomic importance in families of the suborders Polydesmidea and Dalodesmidea (Polydesmida, Diplopoda). AB - Surface structures have rarely been the subject of a comprehensive study in Polydesmida despite their tremendous variety within this order. A number of these peripheral structures are here studied in most families of the suborders Polydesmidea and Dalodesmidea (sensu Hoffman 1980), using scanning electron microscopy. An illustrated description of the surface sculpture of the prozonite, the limbus and the intercalary cuticular micro-scutes on the metazonite is given for the first time for the studied families, together with an account of some other poorly known surface structures. Taken together, these characters allow us to recognize two main groupings of families. The families Ammodesmidae, Cryptodesmidae, Cyrtodesmidae, Haplodesmidae, Oniscodesmidae and Pyrgodesmidae have knobs on the posterior part of the prozonites, a toothed to lobed limbus, and no micro-scutes on the metazonites, wheras the families Fuhrmannodesmidae, Polydesmidae, Dalodesmidae, Macrosternodesmidae, Nearctodesmidae, Opisotretidae and Trichopolydesmidae have no knobs on the posterior part of the prozonites, a spiky or reduced limbus, and intercalary micro-scutes on the metazonites. The results are complemented with literature records and compared with current taxonomic and phylogenetic interpretations of the group. PMID- 22303093 TI - A revision of the millipede genus Riukiupeltis Verhoeff, 1939 (Diplopoda, Polydesmida, Paradoxosomatidae), with comments on the status of related species. AB - The East Asian millipede genus Riukiupeltis Verhoeff, 1939 is revised, and is restricted to a single species, Riukiupeltis jamashinai Verhoeff, 1939. Examination of the type specimens and freshly collected material from the Ryukyu Archipelago and Vietnam show that both subsequently allocated species, Riukiupeltis uenoi Murakami, 1975, and Riukiupeltis falcatus (originally Haplogonosoma falcatum Attems, 1953, reallocated by Jeekel 1968), do not belong to this genus; moreover, they are not even congeneric with each other. According to our morphological observations, including the gonopods, Riukiupeltis uenoi is closer to the widespread Chamberlinius hualienensis Wang, 1956, hence we propose the new combination Chamberlinius uenoi (Murakami, 1975), comb. n.Riukiupeltis falcatus, on the other hand, represents a separate, as yet monotypic, genus Simplogonomorphagen. n., distinct both from Haplogonosoma Brolemann, 1916 sensu Golovatch et al. (1995), and from Verhoeff's original Riukiupeltis. Additionally, Simplogonomorpha falcata (Attems, 1953), comb. n is re-described here based on fresh material from Vietnam. A key and colour habitus-illustrations to all three species are also provided here. PMID- 22303094 TI - Additional moults into 'elongatus' males in laboratory-reared Polydesmus angustus Latzel, 1884 (Diplopoda, Polydesmida, Polydesmidae) - implications for taxonomy. AB - The number of stadia during post-embryonic development is supposed to be fixed in most species of the millipede order Polydesmida. For the first time since 1928, additional moults were observed in two males of Polydesmus angustus Latzel, 1884 reared in the laboratory. These 'elongatus' males sensu Verhoeff reached stadium IX instead of stadium VIII, with addition of a further podous ring (32 pairs of legs). One male had well-developed gonopods at stadium VIII, which regressed at stadium IX; the other had no gonopods at stadium VIII, which developed at stadium IX. The two cases correspond to the 'regressionis' and 'progressionis' forms described by Verhoeff in Polydesmus complanatus (Linnaeus, 1761), which confirms entirely his results. Additional moults appear to be associated with small body sizes and possible underlying mechanisms are discussed. Comparisons between millipede orders indicate that post-embryonic development is less strictly canalized in Polydesmida than in Chordeumatida. This implies that the adult number of body rings is of limited taxonomic value in Polydesmida and should not be viewed as a character of generic importance. PMID- 22303095 TI - Detecting taxonomic signal in an under-utilised character system: geometric morphometrics of the forcipular coxae of Scutigeromorpha (Chilopoda). AB - To date, the forcipules have played almost no role in determining the systematics of scutigeromorph centipedes though in his 1974 review of taxonomic characters Markus Wurmli suggested some potentially informative variation might be found in these structures. Geometric morphometric analyses were used to evaluate Wurmli's suggestion, specifically to determine whether the shape of the forcipular coxa contains information useful for diagnosing species. The geometry of the coxae of eight species from the genera Sphendononema, Scutigera, Dendrothereua, Thereuonema, Thereuopoda, Thereuopodina, Allothereua and Parascutigera was characterised using a combination of landmark- and semi-landmark-based sampling methods to summarize group-specific morphological variation. Canonical variates analysis of shape data characterizing the forcipular coxae indicates that these structures differ significantly between taxa at various systematic levels. Models calculated for the canonical variates space facilitate identification of the main shape differences between genera, including overall length/width, curvature of the external coxal margin, and the extent to which the coxofemoral condyle projects laterally. Jackknifed discriminant function analysis demonstrates that forcipular coxal training-set specimens were assigned to correct species in 61% of cases on average, the most accurate assignments being those of Parascutigera (Parascutigera guttata) and Thereuonema (Thereuonema microstoma). The geographically widespread species Thereuopoda longicornis, Sphendononema guildingii, Scutigera coleoptrata, and Dendrothereua linceci exhibit the least diagnostic coxae in our dataset. Thereuopoda longicornis populations sampled from different parts of East and Southeast Asia were significantly discriminated from each other, suggesting that, in this case, extensive synonymy may be obscuring diagnosable inter-species coxal shape differences. PMID- 22303096 TI - A remarkable case of mosaic parapatry in millipedes. AB - The parapatric boundary between Tasmaniosoma compitale Mesibov, 2010 and Tasmaniosoma hickmanorum Mesibov, 2010 (Polydesmida: Dalodesmidae) in northwest Tasmania was mapped in preparation for field studies of parapatry and speciation. Both millipede species can be collected as adults throughout the year, are often abundant in eucalypt forest and tolerate major habitat disturbance. The parapatric boundary between the two species is ca 100 m wide in well-sampled sections and ca 230 km long. It runs from sea level to 600-700 m elevation, crosses most of the river catchments in northwest Tasmania and several major geological boundaries, and one portion of the boundary runs along a steep rainfall gradient. The location of the boundary is estimated here from scattered sample points using a method based on Delaunay triangulation. PMID- 22303097 TI - Two remarkable new species of Penicillata (Diplopoda, Polyxenida) from Table Mountain National Park (Cape Town, South Africa). AB - Two new species of the families Polyxenidae and Synxenidae, are described from Table Mountain National Park, South Africa. Propolyxenus squamatussp. n. (Polyxenidae) has tergites I-X mostly covered by scale-shaped trichomes directed caudally, a character previously known only in Synxenidae. The structure of scale shaped dorsal trichomes is different to that of the scales in Phryssonotus and Condexenus species. Phryssonotus brevicapensissp. n. (Synxenidae) is the only known species of the genus Phryssonotus having 11 tergites, (including collum and telson) and 15 pairs of legs, as in Condexenus biramipalpus Nguyen Duy-Jacquemin, 2006. These two species therefore appear to occupy an intermediate position between Phryssonotus (12 tergites) and Polyxenoidea (maximum of 11 tergites). PMID- 22303098 TI - The genus Unixenus Jones, 1944 (Diplopoda, Penicillata, Polyxenida) in Australia. AB - The penicillate genus Unixenus Jones, 1944 is widespread, with species found in Africa, Madagascar, India and Australia. Each of the two Australian species was originally described from single samples from Western Australia. In this study, collections of Penicillata from museums in all states of Australia were examined to provide further details of the two described species, to revise the diagnoses for both the genus and the species, and to better understand the distribution of the two species in Australia. In addition, two new species Unixenus karajinensissp. n. and Unixenus corticolussp. n. are described. PMID- 22303099 TI - Barcoding Fauna Bavarica: Myriapoda - a contribution to DNA sequence-based identifications of centipedes and millipedes (Chilopoda, Diplopoda). AB - We give a first account of our ongoing barcoding activities on Bavarian myriapods in the framework of the Barcoding Fauna Bavarica project and IBOL, the International Barcode of Life. Having analyzed 126 taxa (including 122 species) belonging to all major German chilopod and diplopod lineages, often using four or more specimens each, at the moment our species stock includes 82% of the diplopods and 65% of the chilopods found in Bavaria, southern Germany. The partial COI sequences allow correct identification of more than 95% of the current set of Bavarian species. Moreover, most of the myriapod orders and families appear as distinct clades in neighbour-joining trees, although the phylogenetic relationships between them are not always depicted correctly. We give examples of (1) high interspecific sequence variability among closely related species; (2) low interspecific variability in some chordeumatidan genera, indicating that recent speciations cannot be resolved with certainty using COI DNA barcodes; (3) high intraspecific variation in some genera, suggesting the existence of cryptic lineages; and (4) the possible polyphyly of some taxa, i.e. the chordeumatidan genus Ochogona. This shows that, in addition to species identification, our data may be useful in various ways in the context of species delimitations, taxonomic revisions and analyses of ongoing speciation processes. PMID- 22303100 TI - Body size of Chrysomelidae (Coleoptera, Insecta) in areas with different levels of conservation in South Brazil. AB - Body size is correlated with many species traits such as morphology, physiology, life history and abundance as well; it is one of the most discussed topics in macroecological studies. The aim of this paper was to analyze the body size distribution of Chrysomelidae, caught with Malaise traps during two years in four areas with different levels of conservation in the Araucaria Forest, Parana, Brazil, determining if body size is a good predictor of abundance, and if body size could be used to indicate environmental quality. Body size was considered the total length of the specimen from the anterior region of head to the apex of abdomen/elytron. Measurements were taken for up to ten specimens of each species for each area and for all specimens of those species represented by fewer than ten individuals. The highest abundance and richness of Chrysomelidae were obtained in the lowest body size classes. This herbivorous group showed a trend toward a decrease in body size with increasing abundance, but body size was not a good predictor of its abundance. There was a trend toward a decrease in body size from the less to the most conserved areas; however, the definition of a pattern in successional areas not seems to be entirely clear. PMID- 22303101 TI - Altitudinal and temporal distribution of Plagiometriona Spaeth, 1899 (Coleoptera, Chrysomelidae, Cassidinae) in a tropical forest in southeast Brazil. AB - Species richness and abundance of seven Plagiometriona species on their host plants were studied along a single trail in the mountainous Serra dos Orgaos National Park in the State of Rio de Janeiro, Brazil. Six sites were chosen along an altitudinal gradient ranging from 1300 m to 2050 m, where all Solanaceae host plants were inspected in search of adults every two months from June 2006 to June 2007. Species richness did not vary clearly with altitude, but abundance increased up to 1800 m, where the highest mean host plant density was found, and abruptly decreased at the last elevational site. Most species showed a restricted distribution and just one occurred across the entire gradient. For at least four species, altitudinal distribution seems to be strongly related to host plant availability, while for the others it is difficult to access which factors are decisive, due to their low numbers. Only in October all species were found in the field, although February was the month with the highest total abundance. Over the course of the study, the greatest abundances were recorded from October to February, comprehending the hottest and rainiest months, and the lowest abundances were found from June to August, which include the coldest and driest months. Thus, species seasonal distribution, supported by other studies in the same area, seems to be related to the local climate. PMID- 22303102 TI - Rhyparida foaensis (Jolivet, Verma & Mille, 2007), comb. n. (Coleoptera, Chrysomelidae) and implications for the colonization of New Caledonia. AB - The study of external morphology of the New Caledonian leaf beetle Dematochroma foaensis Jolivet, Verma & Mille (Chrysomelidae, Eumolpinae, Colaspoidini) substantiates its new combination into the genus Rhyparida Baly (Chrysomelidae, Eumolpinae, Nodinini). The species is redescribed here to highlight characters important for suprageneric diagnosis. This is the second species of Nodinini found in New Caledonia, otherwise rich in species of Colaspoidini, raising questions about the paucity of Rhyparida and this tribe in New Caledonian fauna, when they are dominant in surrounding archipelagoes, and very rich in potential source areas such as Australia and New Guinea. Some alternative explanations for this pattern are advanced, serving as alternative hypotheses until our knowledge on the ecology of these species improves or supported phylogenetic scenarios become available for this group. PMID- 22303103 TI - Hispines (chrysomelidae, cassidinae) of la selva biological station, costa rica. AB - Survey work from 1992-2001 identified 139 species of hispines at the lowland part of La Selva Biological Station, Costa Rica. The tribe Cephaloleiini was the most speciose with 58 species (41.7%) followed by the Chalepini with 55 (39.5%). The fauna is most closely related to that in South America but with some genera which are more speciose in the Nearctic Region. Plant associations are known for 88 (63.3%) of the species but many of these are merely collecting records, not host plant associations. The first plant associations are reported for Alurnus ornatus, Alurnus salvini, and Acentroptera nevermanni. PMID- 22303104 TI - Cytogenetics, cytotaxonomy and chromosomal evolution of Chrysomelinae revisited (Coleoptera, Chrysomelidae). AB - Nearly 260 taxa and chromosomal races of subfamily Chrysomelinae have been chromosomally analyzed showing a wide range of diploid numbers from 2n = 12 to 2n = 50, and four types of male sex-chromosome systems. with the parachute-like ones Xy(p) and XY(p) clearly prevailing (79.0%), but with the XO well represented too (19.75%). The modal haploid number for chrysomelines is n = 12 (34.2%) although it is not probably the presumed most plesiomorph for the whole subfamily, because in tribe Timarchini the modal number is n = 10 (53.6%) and in subtribe Chrysomelina n = 17 (65.7%). Some well sampled genera, such as Timarcha, Chrysolina and Cyrtonus, are variable in diploid numbers, whereas others, like Chrysomela, Paropsisterna, Oreina and Leptinotarsa, are conservative and these differences are discussed. The main shifts in the chromosomal evolution of Chrysomelinae seems to be centric fissions and pericentric inversions but other changes as centric fusions are also clearly demonstrated. The biarmed chromosome shape is the prevalent condition, as found in most Coleoptera, although a fair number of species hold a few uniarmed chromosomes at least. A significant negative correlation between the haploid numbers and the asymmetry in size of karyotypes (r = -0.74) has been found from a large sample of 63 checked species of ten different genera. Therefore, the increases in haploid number are generally associated with a higher karyotype symmetry. PMID- 22303105 TI - The adipokinetic hormone family in Chrysomeloidea: structural and functional considerations. AB - The presented work is a hybrid of an overview and an original research paper on peptides belonging to the adipokinetic hormone (AKH) family that are present in the corpora cardiaca of Chrysomeloidea. First, we introduce the AKH/red pigment concentrating hormone (RPCH) peptide family. Second, we collate the available primary sequence data on AKH peptides in Cerambycidae and Chrysomelidae, and we present new sequencing data (from previously unstudied species) obtained by liquid-chromatography coupled with ion trap electrospray ionisation mass spectrometry. Our expanded data set encompasses the primary structure of AKHs from seven species of Cerambycidae and three species of Chrysomelidae. All of these species synthesise the octapeptide code-named Peram-CAH-I (pGlu-Val-Asn-Phe Ser-Pro-Asn-Trp amide). Whereas this is the sole AKH peptide in Cerambycidae, Chrysomelidae demonstrate a probable event of AKH gene duplication, thereby giving rise to an additional AKH. This second AKH peptide may be either Emppe-AKH (pGlu-Val-Asn-Phe-Thr-Pro-Asn-Trp amide) or Peram-CAH-II (pGlu-Leu-Thr-Phe-Thr Pro-Asn-Trp amide). The peptide distribution and structural data suggest that both families are closely related and that Peram-CAH-I is the ancestral peptide. We hypothesise on the molecular evolution of Emppe-AKH and Peram-CAH-II from the ancestral peptide due to nonsynonymous missense single nucleotide polymorphism in the nucleotide coding sequence of prepro-AKH. Finally, we review the biological significance of the AKH peptides as hyperprolinaemic hormones in Chrysomeloidea, i.e. they cause an increase in the circulating concentration of proline. The mobilisation of proline has been demonstrated during flight in both cerambycid and chrysomelid beetles. PMID- 22303106 TI - Biology of Blepharida-group flea beetles with first notes on natural history of Podontia congregata Baly, 1865 an endemic flea beetle from southern India (Coleoptera, Chrysomelidae, Galerucinae, Alticini). AB - The biology, host plants, and pest status of Podontia Dalman, 1824 species are reviewed. Natural history of Podontia congregata Baly, 1865 a flea beetle endemic to southern India, is reported for the first time. It is distributed from the Western Ghats Mountains westward to the plains. Clusiaceae is reported as a new host plant family for Blepharida-group species, with Garcinia gummi-gutta (L.) N. Robson (Clusiaceae) as the host plant for Podontia congregata. Pentatomid bugs attack the larvae but not eggs, pupae, or adults. A new egg parasitoid species, Ooencyrtus keralensis Hayat and Prathapan, 2010 (Hymenoptera: Encyrtidae), was discovered. Aspects of Podontia congregata host selection, life cycle, and larval fecal defenses are consistent with its inclusion in the Blepharida-genus group. PMID- 22303107 TI - Types of geographical distribution of leaf beetles (Chrysomelidae) in Central Europe. AB - A comparison of the geographical distribution patterns of 647 species of Chrysomelidae in Central Europe revealed 13 types of distribution: (1) widely distributed, (2) southern, (3) southeastern, (4) southwestern, (5) northern, (6) eastern, (7) south east quarter, (8) south west quarter, (9) fragmented, (10) montane, (11) subalpine & alpine, (12) scattered, (13) unusual, and irregular patterns produced by insufficient data. Some of these distributions are trivial (e. g. northern, eastern, etc., alpine) but others are surprising. Some cannot be explained, e. g. the remarkable gaps in the distribution of Chrysolina limbata (Fabricius, 1775) and in Aphthona nonstriata (Goeze, 1777). Although our 63.000 records are necessarily tentative, we found that the distribution maps from these data reflect in many cases the common knowledge on the occurrence of leaf beetles in specific areas. PMID- 22303108 TI - On whose shoulders we stand - the pioneering entomological discoveries of Karoly Sajo. AB - The excellence of Karoly Sajo as a researcher into Hungary's natural history has been undeservedly neglected. Yet he did lasting work, especially in entomology, and a number of his discoveries and initiatives were before their time.Born in 1851 in Gyor, he received his secondary education there and went to Pest University. He taught in a grammar school in 1877-88 before spending seven years as an entomologist at the National Phylloxera Experimental Station, later the Royal Hungarian State Entomological Station. Pensioned off at his own request in 1895, he moved to Orszentmiklos, where he continued making entomological observations on his own farm and wrote the bulk of his published materials: almost 500 longer or shorter notes, articles and books, mainly on entomological subjects.Sajo was among the first in the world to publish in 1896 a study of how the weather affects living organisms, entitled Living Barometers. His Sleep in Insects, which appeared in the same year, described his discovery, from 1895 observations of the red turnip beetle, Entomoscelis adonidis (Pallas, 1771), of aestivation in insects - in present-day terms diapause.It was a great loss to universal entomology when Sajo ceased publishing about 25 years before his death. His unpublished notes, with his library and correspondence, were destroyed in the World War II. His surviving insect collection is now kept in the Hungarian Natural History Museum, Budapest. PMID- 22303109 TI - A revision of the stylasteridae (cnidaria, hydrozoa, filifera) from alaska and adjacent waters. AB - The stylasterid fauna of Alaska is revised, consisting of the description or redescription and illustration of 21 species, one additional subspecies, and a geographically adjacent species: Stylaster venustus. Six new species and one new subspecies are described: Errinopora fisheri, Errinopora undulata, Errinopora disticha, Errinopora dichotoma, Stylaster crassiseptum, Stylaster repandus, and Stylaster parageus columbiensis. Four subspecies are raised to species rank: Stylaster leptostylus, Stylaster trachystomus, Stylaster parageus, and Distichopora japonica, and five species and one subspecies were synonymized. A dichotomous key to the Errinopora species and tabular keys to the Errinopora and Alaskan Stylaster species are provided. The focus of the study was on the stylasterids from Alaska, primarily those from the diverse Aleutian Islands, but also including records from British Columbia. This is the first revisionary work on this fauna since the seminal report by Fisher in 1938. PMID- 22303110 TI - New records of water mites of the family Sperchontidae Thor, 1900 from China (Acari, Hydrachnidia), with descriptions of two new species. AB - Five species of water mites of the family Sperchontidae Thor, 1900 are reported from China. Two of them are new to science, Sperchon (Sperchon) orbipatellasp.n. and Sperchon (Sperchon) urumqiensissp. n., and the other three are new to China, i.e., Sperchon (Palpisperchon) nikkoensis Imamura, 1976, Sperchon (Sperchon) sounkyo Imamura, 1954 and Sperchonopsis (Sperchonopsella) whiteshellensis Conroy, 1991. The first descriptions of the female of Sperchon nikkoensis and the male of Sperchon sounkyo are also given. The subgenus Sperchonopsella Conroy is new to the fauna of China. PMID- 22303111 TI - A new genus and species of termites (Isoptera, Termitidae, Nasutitermitinae) from the rainforest of northern Peru. AB - A new genus and species of nasutitermitine termites are described and illustrated, based on soldier and worker characters. Sinqasapatermesgen. n., can be distinguished from all other nasutitermitine genera by its singular worker gut coiling and enteric valve characters: distal margin of the enteric valve not everted into the paunch but bending towards the ileum, that is, directed against the flow of food; enteric valve armature with one ring of six equal subtriangularly-shaped ridges, each ridge with short spines on the entire surface; enteric valve armature situatedonexternal face of cone, facing the internal ileum wall; enteric valve seating tri-lobed and separated from remaining portionof the paunch; paunch subdivided. Sinqasapatermes sachaesp. n., was collected on a tree in a very narrow flattened tunnel that was well concealed beneath lichens in a northern Peru rainforest (Arcadia, Loreto Province). PMID- 22303112 TI - Sinosciapus from Taiwan with description of a new species (Diptera, Dolichopodidae). AB - Sinosciapus liuaesp. n. is newly described from Taiwan. The genus Sinosciapus is discussed and a key to the three known Oriental species is provided. PMID- 22303113 TI - Revision of the world species of Zambion (Hymenoptera, Ichneumonidae, Tryphoninae). AB - The world species of Zambion Kasparyan (Hymenoptera: Ichneumonidae: Tryphoninae) are revised including re-descriptions of Zambion monodon Kasparyan and Zambion hirtum Delobel. Five new species are described: Zambion kasparyanisp. n., Zambion rogerisp. n., Zambion eileenaesp. n., Zambion wahlisp. n. andZambion broadisp. n. A key to species is provided. The genus is endemic to Africa (Angola to Kenya) and is one of only three genera of the tribe Tryphonini recorded from the Afrotropical region. PMID- 22303114 TI - Euglossa williamsi, a new species of orchid bee from the Amazon Basin of Ecuador and Peru, with notes on its taxonomic association and biogeography (Hymenoptera, Apidae). AB - Euglossa williamsisp. n. is here described from the lowland Amazonian region in Ecuador and Peru, and as part of a small species assemblage within Euglossa consisting of Euglossa dodsoni Moure and Euglossa obtusa Dressler. An identification key to the males of the group is provided plus detailed figures of the new species and representative illustrations for the others. A brief discussion of the taxonomic and biogeographical implications of the new species is provided. New records in Honduras and Nicaragua are provided for the related Euglossa dodsoni. PMID- 22303115 TI - New species of the Eastern Hemisphere genera Afroheriades and Noteriades (Hymenoptera, Megachilidae), with keys to species of the former. AB - New species of the rarely encountered megachilid genera Afroheriades Peters from South Africa, Afroheriades hyalinussp. n., and Noteriades Cockerell from Myanmar and Thailand, Noteriades jenniferaesp. n. and Noteriades spinosussp. n., are described and illustrated. The species are described to make their names available for forthcoming publications on phylogenetic studies of the family Megachilidae. Taxonomic notes and a comparative diagnosis for each genus are presented. Afroheriades hennigi (Peters) and Afroheriades reicherti (Brauns) are new junior synonyms of Afroheriades dolichocephalus (Friese). A key to the known species of Afroheriades is provided. PMID- 22303116 TI - Review of Anhoplocampa Wei (Hymenoptera, Tenthredinidae), with description of a new species and a new combination. AB - Anhoplocampa is redescribed based on new material. Anhoplocampa bicoloricornissp. n. from China is described. Anhoplocampa yunanensis (Haris & Roller, 1999), comb. n. is transferred from Trichiocampus. A key to species of Anhoplocampa is provided. The differences between Anhoplocampa and Trichiocampus Hartig, 1837, Priophorus Dahlbom, 1835, Hoplocampa Hartig, 1837 and Renonerva Wei & Nie, 1998 are briefly discussed. PMID- 22303117 TI - A new horsehair worm, Chordodes formosanus sp. n. (Nematomorpha, Gordiida) from Hierodula mantids of Taiwan and Japan with redescription of a closely related species, Chordodes japonensis. AB - A new species of horsehair worm, Chordodes formosanussp. n., is described and compared to a closely related species, Chordodes japonensis. Although both species possess the same six cuticular structures of areoles on the surface, the significantly longer filaments on the female crowned areoles can be used as diagnostic characters for the new species. The different taxonomic status of these two species was also confirmed after analyzing the partial cytochrome oxidase subunit I sequence, and the mantid hosts, which are respectively limited to the genus Tenodera for Chordodes japonensis and Hierodula for Chordodes formosanussp. n. In addition, the immature stages of eggs and larvae of the new species are also described and discussed in detail. PMID- 22303118 TI - Further records of non-cryptic New Zealand earthworms. AB - Current descriptions add natives Aporodrilus aoteasp. n., Aporodrilus pongasp. n. and Notoscolex repangasp. n., plus new exotic records to the numbers of megadrile earthworms known from New Zealand, which are now raised from 193 to 222 species in five families, viz: Acanthodrilidae, Octochaetidae and Megascolecidae, plus Lumbricidae and Glossoscolecidae for exotics. Overlooked spermathecal diverticula have been located for Notoscolex equestris Benham, 1942 and for Megascolex animae Lee, 1959 and non-tubular prostrates were misconstrued as tubular in Megascolides tasmani Lee, 1959. Of these latter three species, a lectotype is designated for Notoscolex equestris and holotypes of the other two are briefly redescribed. Whereas Megascolides tasmani now belongs in Notoscolex Fletcher, 1887 and Megascolides animae belongs in Anisochaeta Beddard, 1890, further lack of dorsal pores in Notoscolex equestris as with Notoscolex esculentus (Benham, 1904) and Notoscolex mortenseni (Michaelsen, 1924) newly qualifies all three as additional combs. novae in primarily Tasmanian genus Aporodrilus Blakemore, 2000. PMID- 22303119 TI - First record of the subgenus Damaeus (Paradamaeus) Bulanova-Zachvatkina (Oribatida, Damaeidae) from China, with description of a new species. AB - A new species Damaeus (Paradamaeus) yushuensissp. n. is described from Three Rivers' Headwaters National Natural Reserve, Qinghai province, China. This is the first record of this subgenus in China. A key is given to distinguish all species of the genus. PMID- 22303120 TI - Descriptions of a new Brazilian Tacora species and the female of Tacora saturata, and a key to the species of the genus (Insecta, Hemiptera, Cicadellidae, Cicadellini). AB - Tacora johanni, a new species from Rondonia State, North Brazil, is described and illustrated. The new species can be recognized by the male genital features, especially the subgenital plates with the basal half distinctly expanded and with outer lateral margin round, the long and slender preapical pygofer process, and the styles with apical half strongly curved. Also, the genus is recorded for the first time from Venezuela, based on specimens of Tacora saturata Young, 1977, while the female of this species (here described in detail for the first time) shows two unusual features of the genitalia. A key to males of all known Tacora species and a map showing the known distribution of the genus are provided. PMID- 22303121 TI - New genus and species of broad-nosed weevils from Baltic amber and notes on fossils of the subfamily Entiminae (Coleoptera, Curculionidae). AB - Arostropsis groehnigen. et sp. n. is described from Baltic amber and temporarily placed in the tribe Naupactini. It differs from all recent Naupactini genera with open corbels by very short and flattened scape, distinct lateral carina of the pronotum and elytra, and the rostrum distinctly narrower than the head capsule. The shape of head in the extinct genus is somewhat similar to that of the extant Naupactini genera with enclosed corbels (Platyomus Sahlberg, 1823 and Aptolemus Schoenherr, 1842), but differs in the slender body, open corbels, very short antennal scape and epifrons without a median sulcus (only a longitudinal depression is slightly visible). It is also similar to the Tanymecine genus Pandeleteius Schoenherr, 1834 in general appearance, but distinct by the straight anterior edge of the pronotum, lack of postocular spurs, lobes, and vibrissae, a slightly sloping elytral declivity, lateral ridges on the pronotum, subflattened antennal scape, elongate rostrum, and sparsely setose epistome. A new synonymy of the generic names Protonaupactus Zherikhin, 1971 and Sucinophyllobius Wanat & Borowiec, 1986, syn. n., is established. The Madagascan genus Corecaulus Fairmaire, 1903 is transferred from the tribe Naupactini to the Brachyderini because of its connate claws and the similarity in chaetotaxy of the epistomal area with African and Madagascar Brachyderini genera. A key to the identification of known Baltic amber genera of Entiminae is proposed. A checklist of the prepleistocene fossil Entiminae, based on V.V. Zherikhin's data, with remarks and corrections, is presented. PMID- 22303122 TI - Revision of New World Species of the Shore-fly Subgenus Allotrichoma Becker of the Genus Allotrichoma with Description of the Subgenus Neotrichoma (Diptera, Ephydridae, Hecamedini). AB - The New World species of the subgenera Allotrichoma Becker and Neotrichoma (new subgenus) are revised, including a phylogenetic analysis of the species groups and subgenera within the genus Allotrichoma. For phylogenetic perspective and to document the monophyly of the genus Allotrichoma and its included subgenera and species groups, we also provide a cladistic analysis of genera within the tribe Hecamedini. The ingroup included seven exemplar congeners from within Allotrichoma. Outgroup sampling included exemplars of other genera within Hecamedini and from the putative sister group, Lipochaetini, and to root the analysis, we used an exemplar of the tribe Discocerinini. Analyses with successive weighting and implied weighting recovered a monophyletic Allotrichoma and indicated clades within the genus. Eight new species are described (type locality in parenthesis): Allotrichoma bifurcatum (Utah. Utah: Lake Shore (40 degrees 06.9'N, 111 degrees 41.8'W; 1370 m)), Allotrichoma dynatum (Oregon. Benton: Finley National Wildlife Refuge (44 degrees 24.6'N, 123 degrees 19.5'W)), Allotrichoma occidentale (Oregon. Lake: Lakeview (44 km E; Drake Creek; 42 degrees 11'N, 119 degrees 59.3'W)), Allotrichoma robustum (California. Kern: Kern River (35 degrees 16.1'N, 119 degrees 18.4'W)), Allotrichoma sabroskyi (New Mexico. Sandoval: La Cueva (Junction of Highways 126 and 4; 35 degrees 52'N, 106 degrees 38.4'W; 2342 m)), Allotrichoma wallowa (Oregon Baker: Goose Creek (35 km E Baker City; 44 degrees 49.2'N, 117 degrees 27.79'W; 825 m)), Allotrichoma baliops (Florida. Monroe: Key West (Willie Ward Park; 24 degrees 32.9'N, 81 degrees 47.9'W)), and Allotrichoma insulare (Dominica. Cabrits Swamp (15 degrees 35'N, 61 degrees 29'W)). Within Allotrichoma, we recognize three subgenera of which one, Neotrichoma (type species: Allotrichoma atrilabre), is newly described. All known species from the New World are described with an emphasis on structures of the male terminalia, which are fully illustrated. Detailed locality data and distribution maps for the New World species are provided. A lectotype is designated for Discocerina simplex Loew and a neotype is designated for Allotrichoma bezzii Becker. Allotrichoma filiforme Becker, Allotrichoma trispinum Becker, and Allotrichoma dahli Beschovski are reported as new synonyms of Allotrichoma simplex (Loew) and Allotrichoma yosemite Cresson is a new synonym of Allotrichoma atrilabre Cresson. We also clarify the status of previously described species, including those with Holarctic distributions. For perspective and to facilitate genus-group and species-group recognition, the tribe Hecamedini is diagnosed and a key to included genera is provided. PMID- 22303123 TI - Review of the Nearctic genus Lacconotus LeConte (Coleoptera, Mycteridae, Eurypinae). AB - Lacconotus LeConte, the sole Nearctic representative of the eurypine Mycteridae, is revised, based on morphological features of adults. The following syn. n. is proposed: Lacconotus pallidus Van Dyke, 1928 = Lacconotus pinicola Horn, 1879. The former is a light-colored form with a southern California distribution. A subgen. n.,Alcconotus, is described for Lacconotus pinicola, producing the following comb. n.: Lacconotus (Alcconotus) pinicola (Horn). A lectotype is designated for Lacconotus pinicola. A key separating the two subgenera and species is provided, as are photographs and illustrations of salient structures of adults, and maps showing collection localities. Lacconotus punctatus is newly recorded in Alabama, Arkansas, Massachusetts, Oklahoma, Texas, and Wisconsin; Lacconotus pinicola is newly recorded in Arizona and Utah in the USA, and Baja California Norte in Mexico. Phenology information shows a north-to-south gradation in occurrence time. PMID- 22303124 TI - Rove beetle subtribes Quediina, Amblyopinina and Tanygnathinina: systematic changes affecting Central European fauna (Coleoptera, Staphylinidae, Staphylinini). AB - In preparation for the new edition of the identification keys of rove beetles of Central Europe (Volume 4 of the "Die Kafer Mitteleuropas"), the following systematic problems affecting the Central European fauna of the tribe Staphylinini are addressed: phylogeny-based, new concepts for the subtribes Quediina and Amblyopinina; status of the subtribe Tanygnathinina; systematic position of the genus Astrapaeus; status of Quedionuchus, the subgenus of Quedius; identity of some species of Quedius and Heterothops. As a result, new wordwide and Central Europe-based diagnoses are given for the subtribes Quediina and Amblyopinina; earlier recognized but not widely accepted synonymies of the genera Quedius and Velleius, and of the species Heterothops praevius and Heterothops niger, are justified; new synonyms are established for: Quedius pseudonigriceps Reitter, 1909 (= Quediusnoricus Bernhauer, 1927, syn. n.); Quedius maurorufus (Gravenhorst, 1806) (= Quedius richteri Korge, 1966, syn. n.); Quedius suturalis Kiesenwetter, 1845 (= Quedius merlini Drugmand & Bruge 1991, syn. n.); lectotypes are designated for Quedius meridiocarpathicus Smetana, 1958, Quedius noricus Bernhauer, 1927, and Quedius pseudonigriceps Reitter, 1909. As a result of synonymy of Quedius and Velleius, the following new combinations are proposed: Quedius amamiensis (Watanabe, 1990), comb. n.; Quedius circumipectus (Cho, 1996), comb. n.; Quedius elongatus (Naomi, 1986), comb. n.; Quedius japonicus (Watanabe, 1990), comb. n.; Quedius pectinatus (Sharp, 1874), comb. n.; Quedius setosus (Sharp, 1889), comb. n.; Quedius simillimus (Fairmaire, 1891), comb. n. As a result of new combinations, Quedius japonicus (Watanabe, 1990) (non Quedius japonicus Sharp, 1874) is replaced with the new name Quedius watanabei Solodovnikov, nom. n., while Quedius pectinatus Lea, 1908 (non Quedius pectinatus (Sharp, 1874)) is replaced with the new name Quedius arthuri Solodovnikov, nom. n. PMID- 22303125 TI - Revision of Tipula (Yamatotipula) stackelbergi Alexander (Diptera, Tipulidae), and a short discussion on subspecies among crane flies. AB - All available type material of Tipula stackelbergi Alexander, Tipula usuriensis Alexander and Tipula subpruinosa Mannheims were examined. Tipula (Yamatotipula) stackelbergistat. rev. is elevated from a subspecies of Tipula (Yamatotipula) pruinosa Wiedemann to a valid species. Two new synonyms are proposed: Tipula usuriensissyn. n. proved to be a junior synonym of. Tipula (Yamatotipula) pruinosa and Tipula subpruinosasyn. n. a junior synonym of Tipula (Yamatotipula) freyana Lackschewitz. Tipula (Yamatotipula) stackelbergi is redescribed, male and female terminalia of Tipula (Yamatotipula) pruinosa are illustrated and discussed. Female terminalia of Tipula (Yamatotipula) freyana are described and illustrated for the first time. A key to both sexes of Tipula (Yamatotipula) stackelbergi and Tipula (Yamatotipula) pruinosa, and a key to females of Tipula (Yamatotipula) chonsaniana, Tipula (Yamatotipula) freyana and Tipula (Yamatotipula) moesta are provided. Subspecies are not uncommon among crane flies, but their ranges and traits are poorly known. An interdisciplinary approach (genetics, ecology, taxonomy) is suggested if subspecific ranks are to be used in tipuloid systematics. PMID- 22303126 TI - A conspectus on the Canacidae (Diptera) of Brazil. AB - Species of Canacidaesensu lato of Brazil are reviewed, including the subfamilies Canacinae and Tethininae. Included are seven species in five genera with two species, Nocticanace austra and Nocticanace packhamorum, from southern Brazil being newly described. To facilitate identification, we have included keys and diagnose to taxa at all levels. PMID- 22303127 TI - A troglomorphic spider from Java (Araneae, Ctenidae, Amauropelma). AB - A new troglomorphic spider from caves in Central Java, Indonesia, is described and placed in the ctenid genus Amauropelma Raven, Stumkat & Gray, until now containing only species from Queensland, Australia. Only juveniles and mature females of the new species are known. We give our reasons for placing the new species in Amauropelma, discuss conflicting characters, and make predictions about the morphology of the as yet undiscovered male that will test our taxonomic hypothesis. The description includes DNA barcode sequence data. PMID- 22303128 TI - Commensal Leucothoidae (Crustacea, Amphipoda) of the Ryukyu Archipelago, Japan. Part I: ascidian-dwellers. AB - Commensal leucothoid amphipods have been collected from the branchial chambers of their ascidian hosts throughout the Ryukyu Archipelago, Japan. Seven new species are described in two genera with valuable location data and host records. An identification key to ascidian-dwelling Leucothoidae of the Ryukyu Archipelago is provided. PMID- 22303129 TI - A new species and first record of the genus Triacanthella Schaffer, 1897 (Collembola, Poduromorpha, Hypogastruridae) for Africa. AB - The first species of the genus Triacanthella to be recorded from Africa is described. Triacanthella madibasp. n. belongs to the Southern Hemisphere group of the genus. It is morphologically closely related to Triacanthella vogeli Weiner & Najt, 1997 from Chile, and appears to be a gondwanian relict. The new species is also the first Triacanthella recorded from a guano habitat. PMID- 22303130 TI - Description of a new species of Platynus Bonelli from the Appalachian Mountains of eastern North America (Coleoptera, Carabidae). AB - A new species of the genus Platynus Bonelli, Platynus daviesi, is described from specimens collected in the Appalachian Mountains. The species is structurally most similar to Platynus parmarginatus Hamilton but differs in having the coloration of the body dorsally darker on average, the elytra proportionally longer and wider, the vertex and disc of pronotum with well impressed microsculpture, the elytral interval 3 with four or five discal setae in most specimens, and the median lobe of aedeagus less curved overall. DNA barcoding was performed on several species of eastern North American Platynus species and Platynus daviesi was found to be genetically distinct from Platynus parmarginatus. A key to the 12 species of Platynus found east of the Mississippi River is provided. PMID- 22303131 TI - Discovery of the genus Meggoleus Townes, 1971 (Hymenoptera, Ichneumonidae, Tersilochinae) in Peru, with the description of two new species. AB - The genus Meggoleus Townes, 1971 (Ichneumonidae, Tersilochinae) currently comprises two species, one from Brazil and one from Gabon. The genus is recorded from Peru for the first time, with a range extension of the type species, Meggoleus spirator Townes, 1971, and the discovery of two new species - Meggoleus fuscatussp. n. and Meggoleus pampahermosensissp. n. A key to the world's species is provided. PMID- 22303132 TI - Circular High-Q Resonating Isotropic Strain Sensors with Large Shift of Resonance Frequency under Stress. AB - We present circular architecture bioimplant strain sensors that facilitate a strong resonance frequency shift with mechanical deformation. The clinical application area of these sensors is for in vivo assessment of bone fractures. Using a rectangular geometry, we obtain a resonance shift of 330 MHz for a single device and 170 MHz for its triplet configuration (with three side-by-side resonators on chip) under an applied load of 3,920 N. Using the same device parameters with a circular isotropic architecture, we achieve a resonance frequency shift of 500 MHz for the single device and 260 MHz for its triplet configuration, demonstrating substantially increased sensitivity. PMID- 22303133 TI - Non-Linearity in Wide Dynamic Range CMOS Image Sensors Utilizing a Partial Charge Transfer Technique. AB - The partial charge transfer technique can expand the dynamic range of a CMOS image sensor by synthesizing two types of signal, namely the long and short accumulation time signals. However the short accumulation time signal obtained from partial transfer operation suffers of non-linearity with respect to the incident light. In this paper, an analysis of the non-linearity in partial charge transfer technique has been carried, and the relationship between dynamic range and the non-linearity is studied. The results show that the non-linearity is caused by two factors, namely the current diffusion, which has an exponential relation with the potential barrier, and the initial condition of photodiodes in which it shows that the error in the high illumination region increases as the ratio of the long to the short accumulation time raises. Moreover, the increment of the saturation level of photodiodes also increases the error in the high illumination region. PMID- 22303134 TI - A featured-based strategy for stereovision matching in sensors with fish-eye lenses for forest environments. AB - This paper describes a novel feature-based stereovision matching process based on a pair of omnidirectional images in forest stands acquired with a stereovision sensor equipped with fish-eye lenses. The stereo analysis problem consists of the following steps: image acquisition, camera modelling, feature extraction, image matching and depth determination. Once the depths of significant points on the trees are obtained, the growing stock volume can be estimated by considering the geometrical camera modelling, which is the final goal. The key steps are feature extraction and image matching. This paper is devoted solely to these two steps. At a first stage a segmentation process extracts the trunks, which are the regions used as features, where each feature is identified through a set of attributes of properties useful for matching. In the second step the features are matched based on the application of the following four well known matching constraints, epipolar, similarity, ordering and uniqueness. The combination of the segmentation and matching processes for this specific kind of sensors make the main contribution of the paper. The method is tested with satisfactory results and compared against the human expert criterion. PMID- 22303135 TI - Acoustic sensor planning for gunshot location in national parks: a pareto front approach. AB - In this paper, we propose a solution for gunshot location in national parks. In Spain there are agencies such as SEPRONA that fight against poaching with considerable success. The DiANa project, which is endorsed by Cabaneros National Park and the SEPRONA service, proposes a system to automatically detect and locate gunshots. This work presents its technical aspects related to network design and planning. The system consists of a network of acoustic sensors that locate gunshots by hyperbolic multi-lateration estimation. The differences in sound time arrivals allow the computation of a low error estimator of gunshot location. The accuracy of this method depends on tight sensor clock synchronization, which an ad-hoc time synchronization protocol provides. On the other hand, since the areas under surveillance are wide, and electric power is scarce, it is necessary to maximize detection coverage and minimize system cost at the same time. Therefore, sensor network planning has two targets, i.e., coverage and cost. We model planning as an unconstrained problem with two objective functions. We determine a set of candidate solutions of interest by combining a derivative-free descent method we have recently proposed with a Pareto front approach. The results are clearly superior to random seeding in a realistic simulation scenario. PMID- 22303136 TI - DNA hybridization sensors based on electrochemical impedance spectroscopy as a detection tool. AB - Recent advances in label free DNA hybridization sensors employing electrochemical impedance spectroscopy (EIS) as a detection tool are reviewed. These sensors are based on the modulation of the blocking ability of an electrode modified with a probe DNA by an analyte, i.e., target DNA. The probe DNA is immobilized on a self assembled monolayer, a conducting polymer film, or a layer of nanostructures on the electrode such that desired probe DNA would selectively hybridize with target DNA. The rate of charge transfer from the electrode thus modified to a redox indicator, e.g., [Fe(CN)(6)](3-/4-), which is measured by EIS in the form of charge transfer resistance (R(ct)), is modulated by whether or not, as well as how much, the intended target DNA is selectively hybridized. Efforts made to enhance the selectivity as well as the sensitivity of DNA sensors and to reduce the EIS measurement time are briefly described along with brief future perspectives in developing DNA sensors. PMID- 22303137 TI - A flexible flow sensor system and its characteristics for fluid mechanics measurements. AB - In this paper, we present a novel micromachined hot-film flow sensor system realized by a technique using a film depositing processes and incorporating a standard printed circuit. Sensor electrodes and electronic circuits are preprinted on a flexible substrate of polyimide (PI), i.e., a flexible printed circuit board (FPCB). The sensing element, which is made of Cr/Ni/Pt with a temperature coefficient of resistance around 2,000 ppm/K, is fabricated on the FPCB by either magnetron sputtering technology or pulsed laser deposition (PLD). The sensor can be packed efficiently at high-density and integrated with signal processing circuits without additional pads. A simple fabrication process using mature technique and materials selection guarantees that the time and costs are greatly reduced. Both steady-state and transient characteristics of the sensors are experimentally tested, and the results presented to validate the effectiveness of the sensors. PMID- 22303138 TI - Determination of viscoelastic property in polyethylene crystallization using a quartz crystal resonator. AB - A new generalized relationship between the viscoelastic properties of an overlayer placed on the electrode interface of a quartz crystal resonator and its resonant characteristic is developed from the mechanics of the quartz movement. The relationship is used to estimate the viscoelastic properties from the experimentally measured resonant characteristic. It is utilized in the estimation of viscosity and elastic shear modulus of a polyethylene overlayer during its crystallization. The measurements are compared with the viscosity and elastic shear modulus of a polyethylene melt measured using a rheometer. It is found that the development of this study is useful in the determination of viscoelastic property of polymer materials by measuring the resonant frequency and conductance of the polymer overlayer placed on the resonator electrode. PMID- 22303139 TI - A capacitive displacement sensing technique for early detection of unbalanced loads in a washing machine. AB - Horizontal axis washing machines are water and energy efficient and becoming popular in the USA. Unlike a vertical axis washer, these do not have an agitator and depend solely on tumbling for the agitation of laundry during the wash cycle. However, due to the constant shifting of laundry during washing, the load distribution is often unbalanced during the high speed spin cycle. We present a displacement-based sensing method to detect unbalance early while the spin rate (rpm) is well below the resonance frequency so that corrective actions may be taken prior to the high speed spin cycle. Experimental and analytical characterizations of the sensor configuration are presented. Results show that the displacement sensor is more appropriate than an accelerometer for this application and offer the potential for a simple, reliable, low cost detection of unbalance. PMID- 22303140 TI - Contact-free Measurement of Heart Rate Variability via a Microwave Sensor. AB - Measures of heart rate variability (HRV) are widely used to assess autonomic nervous system (ANS) function. HRV can be recorded via electrocardiography (ECG), which is both non-invasive and widely available. However, ECG needs three electrodes touching the body of the subjects, which makes them feel nervous and uncomfortable, thus potentially affecting the recording. Contact-free detection of the heartbeat via a microwave sensor constitutes another means of determining the timing of cardiac cycles by continuous monitoring of mechanical contraction of the heart. This technique can measure the heartbeat without any electrodes touching human body and penetrate the clothes at some distances, which in some instances may prove a practical basis for HRV analysis. Comparison of 5-minute recordings demonstrated that there were no significant differences in the temporal, frequency domains and in non-linear dynamic analysis of HRV measures derived from heartbeat and ECG, which suggested this technique may prove a practical alternative to ECG for HRV analysis. PMID- 22303141 TI - Interrelationship of Pyrogenic Polycyclic Aromatic Hydrocarbon (PAH) Contamination in Different Environmental Media. AB - Interrelationships between pyrogenic polycyclic aromatic hydrocarbons (PAHs) were assessed in air, soil, water, sediment, and tree leaves by using multi-media monitoring data. Concurrent concentration measurements were taken bimonthly for a year for the multi-media at urban and suburban sites. PAH level correlations between air and other media were observed at the urban site but were less clear at the suburban site. Considering a closer PAHs distribution/fate characteristics to soil than suspended solids, contamination in sediment seemed to be governed primarily by that in soil. The partitioning of PAHs in waters could be better accounted for by sorption onto black carbon and dissolved organic carbon. PMID- 22303142 TI - Evaporation estimation of rift valley lakes: comparison of models. AB - Evapotranspiration (ET) accounts for a substantial amount of the water flux in the arid and semi-arid regions of the World. Accurate estimation of ET has been a challenge for hydrologists, mainly because of the spatiotemporal variability of the environmental and physical parameters governing the latent heat flux. In addition, most available ET models depend on intensive meteorological information for ET estimation. Such data are not available at the desired spatial and temporal scales in less developed and remote parts of the world. This limitation has necessitated the development of simple models that are less data intensive and provide ET estimates with acceptable level of accuracy. Remote sensing approach can also be applied to large areas where meteorological data are not available and field scale data collection is costly, time consuming and difficult. In areas like the Rift Valley regions of Ethiopia, the applicability of the Simple Method (Abtew Method) of lake evaporation estimation and surface energy balance approach using remote sensing was studied. The Simple Method and a remote sensing-based lake evaporation estimates were compared to the Penman, Energy balance, Pan, Radiation and Complementary Relationship Lake Evaporation (CRLE) methods applied in the region. Results indicate a good correspondence of the models outputs to that of the above methods. Comparison of the 1986 and 2000 monthly lake ET from the Landsat images to the Simple and Penman Methods show that the remote sensing and surface energy balance approach is promising for large scale applications to understand the spatial variation of the latent heat flux. PMID- 22303143 TI - Photoacoustic techniques for trace gas sensing based on semiconductor laser sources. AB - The paper provides an overview on the use of photoacoustic sensors based on semiconductor laser sources for the detection of trace gases. We review the results obtained using standard, differential and quartz enhanced photoacoustic techniques. PMID- 22303144 TI - Bundle Block Adjustment with 3D Natural Cubic Splines. AB - Point-based methods undertaken by experienced human operators are very effective for traditional photogrammetric activities, but they are not appropriate in the autonomous environment of digital photogrammetry. To develop more reliable and accurate techniques, higher level objects with linear features accommodating elements other than points are alternatively adopted for aerial triangulation. Even though recent advanced algorithms provide accurate and reliable linear feature extraction, the use of such features that can consist of complex curve forms is more difficult than extracting a discrete set of points. Control points that are the initial input data, and break points that are end points of segmented curves, are readily obtained. Employment of high level features increases the feasibility of using geometric information and provides access to appropriate analytical solutions for advanced computer technology. PMID- 22303145 TI - Data centric sensor stream reduction for real-time applications in wireless sensor networks. AB - This work presents a data-centric strategy to meet deadlines in soft real-time applications in wireless sensor networks. This strategy considers three main aspects: (i) The design of real-time application to obtain the minimum deadlines; (ii) An analytic model to estimate the ideal sample size used by data-reduction algorithms; and (iii) Two data-centric stream-based sampling algorithms to perform data reduction whenever necessary. Simulation results show that our data centric strategies meet deadlines without loosing data representativeness. PMID- 22303146 TI - Survey of visual and force/tactile control of robots for physical interaction in Spain. AB - Sensors provide robotic systems with the information required to perceive the changes that happen in unstructured environments and modify their actions accordingly. The robotic controllers which process and analyze this sensory information are usually based on three types of sensors (visual, force/torque and tactile) which identify the most widespread robotic control strategies: visual servoing control, force control and tactile control. This paper presents a detailed review on the sensor architectures, algorithmic techniques and applications which have been developed by Spanish researchers in order to implement these mono-sensor and multi-sensor controllers which combine several sensors. PMID- 22303147 TI - Low Magnetic Field Detection Using a CuPt Nano Structure Made on a SiO(2)/Si Structure. AB - A Si/SiO(2)/CuPt structure is formed by depositing a very thin SiO(2) layer between CuPt and P-type Si layers using e-beam evaporation. SEM images show the formation of CuPt nano clusters with an average size of less than 100 nm. This structure shows high sensitivity to applied magnetic fields at 77K and at low and high dc voltages such that magnetic field as low as 6 mT is detected using I-V and I-B measurements. The variation of current with various magnetic field strength at the constant voltage shows also an oscillatory behavior. The sensitivity of this structure to magnetic fields is believed to be due to small nano size of the platinum-copper structures as well as their discrete energy states and the tunneling of carriers into the insulating layer. Our results indicate that this structure may be a good candidate for small, simple, low cost and sensitive low magnetic field detectors. PMID- 22303148 TI - Photoreactions and structural changes of anabaena sensory rhodopsin. AB - Anabaena sensory rhodopsin (ASR) is an archaeal-type rhodopsin found in eubacteria. The gene encoding ASR forms a single operon with ASRT (ASR transducer) which is a 14 kDa soluble protein, suggesting that ASR functions as a photochromic sensor by activating the soluble transducer. This article reviews the detailed photoreaction processes of ASR, which were studied by low temperature Fourier-transform infrared (FTIR) and UV-visible spectroscopy. The former research reveals that the retinal isomerization is similar to bacteriorhodopsin (BR), but the hydrogen-bonding network around the Schiff base and cytoplasmic region is different. The latter study shows the stable photoproduct of the all-trans form is 100% 13-cis, and that of the 13-cis form is 100% all-trans. These results suggest that the structural changes of ASR in the cytoplasmic domain play important roles in the activation of the transducer protein, and photochromic reaction is optimized for its sensor function. PMID- 22303149 TI - SAW RFID-Tags for Mass-Sensitive Detection of Humidity and Vapors. AB - One-port surface acoustic wave (SAW) devices with defined reflector patterns give characteristic signal patterns in the time domain making them identifiable and leading to so-called RFID-Tags. Each sensor responds with a burst of signals, their timed positions giving the identification code, while the amplitudes can be related to the analyte concentration. This paper presents the first combination of such a transducer with chemically sensitive layer materials. These include crosslinked polyvinyl alcohol for determining relative humidity and tert butylcalix[4]arene for detecting solvent vapors coated on the free space between the reflectors. In going from the time domain to the frequency domain by Fourier transformation, changes in frequency and phase lead to sensor responses. Hence, it is possible to measure the concentration of tetrachloroethene in air down to 50 ppm, as well as 1% changes in relative humidity. PMID- 22303150 TI - Molecular sensing by nanoporous crystalline polymers. AB - Chemical sensors are generally based on the integration of suitable sensitive layers and transducing mechanisms. Although inorganic porous materials can be effective, there is significant interest in the use of polymeric materials because of their easy fabrication process, lower costs and mechanical flexibility. However, porous polymeric absorbents are generally amorphous and hence present poor molecular selectivity and undesired changes of mechanical properties as a consequence of large analyte uptake. In this contribution the structure, properties and some possible applications of sensing polymeric films based on nanoporous crystalline phases, which exhibit all identical nanopores, will be reviewed. The main advantages of crystalline nanoporous polymeric materials with respect to their amorphous counterparts are, besides a higher selectivity, the ability to maintain their physical state as well as geometry, even after large guest uptake (up to 10-15 wt%), and the possibility to control guest diffusivity by controlling the orientation of the host polymeric crystalline phase. The final section of the review also describes the ability of suitable polymeric films to act as chirality sensors, i.e., to sense and memorize the presence of non-racemic volatile organic compounds. PMID- 22303151 TI - Application of poincare-mapping of voiced-speech segments for emotion sensing. AB - The following paper introduces a group of novel speech-signal descriptors that reflect phoneme-pronunciation variability and that can be considered as potentially useful features for emotion sensing. The proposed group includes a set of statistical parameters of Poincare maps, derived for formant-frequency evolution and energy evolution of voiced-speech segments. Two groups of Poincare map characteristics were considered in the research: descriptors of sample scatter, which reflect magnitudes of phone-uttering variations and descriptors of cross-correlations that exist among samples and that evaluate consistency of variations. It has been shown that inclusion of the proposed characteristics into the pool of commonly used speech descriptors, results in a noticeable increase-at the level of 10%-in emotion sensing performance. Standard pattern recognition methodology has been adopted for evaluation of the proposed descriptors, with the assumption that three- or four-dimensional feature spaces can provide sufficient emotion sensing. Binary decision trees have been selected for data classification, as they provide with detailed information on emotion-specific discriminative power of various speech descriptors. PMID- 22303152 TI - Use of terrestrial laser scanning technology for long term high precision deformation monitoring. AB - The paper presents a new methodology for high precision monitoring of deformations with a long term perspective using terrestrial laser scanning technology. In order to solve the problem of a stable reference system and to assure the high quality of possible position changes of point clouds, scanning is integrated with two complementary surveying techniques, i.e., high quality static GNSS positioning and precise tacheometry. The case study object where the proposed methodology was tested is a high pressure underground pipeline situated in an area which is geologically unstable. PMID- 22303153 TI - All-plastic electrochemical transistor for glucose sensing using a ferrocene mediator. AB - We demonstrate a glucose sensor based on an organic electrochemical transistor (OECT) in which the channel, source, drain, and gate electrodes are made from the conducting polymer poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS). The OECT employs a ferrocene mediator to shuttle electrons between the enzyme glucose oxidase and a PEDOT:PSS gate electrode. The device can be fabricated using a one-layer patterning process and offers glucose detection down to the micromolar range, consistent with levels present in human saliva. PMID- 22303154 TI - Gas sensors based on semiconducting metal oxide one-dimensional nanostructures. AB - This article provides a comprehensive review of recent (2008 and 2009) progress in gas sensors based on semiconducting metal oxide one-dimensional (1D) nanostructures. During last few years, gas sensors based on semiconducting oxide 1D nanostructures have been widely investigated. Additionally, modified or doped oxide nanowires/nanobelts have also been synthesized and used for gas sensor applications. Moreover, novel device structures such as electronic noses and low power consumption self-heated gas sensors have been invented and their gas sensing performance has also been evaluated. Finally, we also point out some challenges for future investigation and practical application. PMID- 22303155 TI - Locating acoustic events based on large-scale sensor networks. AB - Research on acoustic source localization is actively being conducted to enhance accuracy and coverage. However, the performance is inherently limited due to the use of expensive sensor nodes and inefficient communication methods. This paper proposes an acoustic source localization algorithm for a large area that uses low cost sensor nodes. The proposed mechanism efficiently handles multiple acoustic sources by removing false-positive errors that arise from the different propagation ranges of radio and sound. Extensive outdoor experiments with real hardware validated that the proposed mechanism could localize four acoustic sources within a 3 m error in a 60 m by 60 m area, where conventional systems could hardly achieve similar performance. PMID- 22303156 TI - A Reduced Three Dimensional Model for SAW Sensors Using Finite Element Analysis. AB - A major problem that often arises in modeling Micro Electro Mechanical Systems (MEMS) such as Surface Acoustic Wave (SAW) sensors using Finite Element Analysis (FEA) is the extensive computational capacity required. In this study a new approach is adopted to significantly reduce the computational capacity needed for analyzing the response of a SAW sensor using the finite element (FE) method. The approach is based on the plane wave solution where the properties of the wave vary in two dimensions and are uniform along the thickness of the device. The plane wave solution therefore allows the thickness of the SAW device model to be minimized; the model is referred to as a Reduced 3D Model (R3D). Various configurations of this novel R3D model are developed and compared with theoretical and experimental frequency data and the results show very good agreement. In addition, two-dimensional (2D) models with similar configurations to the R3D are developed for comparison since the 2D approach is widely adopted in the literature as a computationally inexpensive approach to model SAW sensors using the FE method. Results illustrate that the R3D model is capable of capturing the SAW response more accurately than the 2D model; this is demonstrated by comparison of centre frequency and insertion loss values. These results are very encouraging and indicate that the R3D model is capable of capturing the MEMS-based SAW sensor response without being computationally expensive. PMID- 22303157 TI - Polyester sulphonic Acid interstitial nanocomposite platform for peroxide biosensor. AB - A novel enzyme immobilization platform was prepared on a platinum disk working electrode by polymerizing aniline inside the interstitial pores of polyester sulphonic acid sodium salt (PESA). Scanning electron microscopy study showed the formation of homogeneous sulphonated polyaniline (PANI) nanotubes (~90 nm) and thermogravimetric analysis (TGA) confirmed that the nanotubes were stable up to 230 degrees C. The PANI:PESA nanocomposite showed a quasi-reversible redox behaviour in phosphate buffer saline. Horseradish peroxidase (HRP) was immobilized on to this modified electrode for hydrogen peroxide detection. The biosensor gave a sensitivity of 1.33 MUA (MUM)(-1) and a detection limit of 0.185 MUM for H(2)O(2). Stability experiments showed that the biosensor retained more than 64% of its initial sensitivity over four days of storage at 4 degrees C. PMID- 22303158 TI - A lyapunov-based extension to particle swarm dynamics for continuous function optimization. AB - The paper proposes three alternative extensions to the classical global-best particle swarm optimization dynamics, and compares their relative performance with the standard particle swarm algorithm. The first extension, which readily follows from the well-known Lyapunov's stability theorem, provides a mathematical basis of the particle dynamics with a guaranteed convergence at an optimum. The inclusion of local and global attractors to this dynamics leads to faster convergence speed and better accuracy than the classical one. The second extension augments the velocity adaptation equation by a negative randomly weighted positional term of individual particle, while the third extension considers the negative positional term in place of the inertial term. Computer simulations further reveal that the last two extensions outperform both the classical and the first extension in terms of convergence speed and accuracy. PMID- 22303159 TI - A polygon model for wireless sensor network deployment with directional sensing areas. AB - The modeling of the sensing area of a sensor node is essential for the deployment algorithm of wireless sensor networks (WSNs). In this paper, a polygon model is proposed for the sensor node with directional sensing area. In addition, a WSN deployment algorithm is presented with topology control and scoring mechanisms to maintain network connectivity and improve sensing coverage rate. To evaluate the proposed polygon model and WSN deployment algorithm, a simulation is conducted. The simulation results show that the proposed polygon model outperforms the existed disk model and circular sector model in terms of the maximum sensing coverage rate. PMID- 22303160 TI - A neuro-fuzzy system for extracting environment features based on ultrasonic sensors. AB - In this paper, a method to extract features of the environment based on ultrasonic sensors is presented. A 3D model of a set of sonar systems and a workplace has been developed. The target of this approach is to extract in a short time, while the vehicle is moving, features of the environment. Particularly, the approach shown in this paper has been focused on determining walls and corners, which are very common environment features. In order to prove the viability of the devised approach, a 3D simulated environment has been built. A Neuro-Fuzzy strategy has been used in order to extract environment features from this simulated model. Several trials have been carried out, obtaining satisfactory results in this context. After that, some experimental tests have been conducted using a real vehicle with a set of sonar systems. The obtained results reveal the satisfactory generalization properties of the approach in this case. PMID- 22303161 TI - Real-time accumulative computation motion detectors. AB - The neurally inspired accumulative computation (AC) method and its application to motion detection have been introduced in the past years. This paper revisits the fact that many researchers have explored the relationship between neural networks and finite state machines. Indeed, finite state machines constitute the best characterized computational model, whereas artificial neural networks have become a very successful tool for modeling and problem solving. The article shows how to reach real-time performance after using a model described as a finite state machine. This paper introduces two steps towards that direction: (a) A simplification of the general AC method is performed by formally transforming it into a finite state machine. (b) A hardware implementation in FPGA of such a designed AC module, as well as an 8-AC motion detector, providing promising performance results. We also offer two case studies of the use of AC motion detectors in surveillance applications, namely infrared-based people segmentation and color-based people tracking, respectively. PMID- 22303162 TI - On-chip immunoassay for determination of urinary albumin. AB - An immunoassay performed on a portable microfluidic device was evaluated for the determination of urinary albumin. An increase in absorbance at 500 nm resulting from immunoagglutination was monitored directly on the poly(dimethylsiloxane) (PDMS) microchip using a portable miniature fibre-optic spectrometer. A calibration curve was linear up to 10 mg L(-1) (r(2) = 0.993), with a detection limit of 0.81 mg L(-1) (S/N = 3). The proposed system showed good precision, with relative standard deviations (RSDs) of 5.1%, when evaluated with 10 mg L(-1) albumin (n = 10). Determination of urinary albumin with the proposed system gave results highly similar to those determined by the conventional spectrophotometric method using immunoturbidimetric detection (r(2) = 0.995; n = 15). PMID- 22303163 TI - Sensors for 3D Imaging: Metric Evaluation and Calibration of a CCD/CMOS Time-of Flight Camera. AB - 3D imaging with Time-of-Flight (ToF) cameras is a promising recent technique which allows 3D point clouds to be acquired at video frame rates. However, the distance measurements of these devices are often affected by some systematic errors which decrease the quality of the acquired data. In order to evaluate these errors, some experimental tests on a CCD/CMOS ToF camera sensor, the SwissRanger (SR)-4000 camera, were performed and reported in this paper. In particular, two main aspects are treated: the calibration of the distance measurements of the SR-4000 camera, which deals with evaluation of the camera warm up time period, the distance measurement error evaluation and a study of the influence on distance measurements of the camera orientation with respect to the observed object; the second aspect concerns the photogrammetric calibration of the amplitude images delivered by the camera using a purpose-built multi resolution field made of high contrast targets. PMID- 22303164 TI - Registration Combining Wide and Narrow Baseline Feature Tracking Techniques for Markerless AR Systems. AB - Augmented reality (AR) is a field of computer research which deals with the combination of real world and computer generated data. Registration is one of the most difficult problems currently limiting the usability of AR systems. In this paper, we propose a novel natural feature tracking based registration method for AR applications. The proposed method has following advantages: (1) it is simple and efficient, as no man-made markers are needed for both indoor and outdoor AR applications; moreover, it can work with arbitrary geometric shapes including planar, near planar and non planar structures which really enhance the usability of AR systems. (2) Thanks to the reduced SIFT based augmented optical flow tracker, the virtual scene can still be augmented on the specified areas even under the circumstances of occlusion and large changes in viewpoint during the entire process. (3) It is easy to use, because the adaptive classification tree based matching strategy can give us fast and accurate initialization, even when the initial camera is different from the reference image to a large degree. Experimental evaluations validate the performance of the proposed method for online pose tracking and augmentation. PMID- 22303165 TI - Multi-hop routing mechanism for reliable sensor computing. AB - Current research on routing in wireless sensor computing concentrates on increasing the service lifetime, enabling scalability for large number of sensors and supporting fault tolerance for battery exhaustion and broken nodes. A sensor node is naturally exposed to various sources of unreliable communication channels and node failures. Sensor nodes have many failure modes, and each failure degrades the network performance. This work develops a novel mechanism, called Reliable Routing Mechanism (RRM), based on a hybrid cluster-based routing protocol to specify the best reliable routing path for sensor computing. Table driven intra-cluster routing and on-demand inter-cluster routing are combined by changing the relationship between clusters for sensor computing. Applying a reliable routing mechanism in sensor computing can improve routing reliability, maintain low packet loss, minimize management overhead and save energy consumption. Simulation results indicate that the reliability of the proposed RRM mechanism is around 25% higher than that of the Dynamic Source Routing (DSR) and ad hoc On-demand Distance Vector routing (AODV) mechanisms. PMID- 22303166 TI - Remote sensing and skywave digital communication from antarctica. AB - This paper presents an overview of the research activities undertaken by La Salle and the Ebro Observatory in the field of remote sensing. On 2003 we started a research project with two main objectives: implement a long-haul oblique ionospheric sounder and transmit the data from remote sensors located at the Spanish Antarctic station Juan Carlos I to Spain. The paper focuses on a study of feasibility of two possible physical layer candidates for the skywave link between both points. A DS-SS based solution and an OFDM based solution are considered to achieve a reliable low-power low-rate communication system between Antarctica and Spain. PMID- 22303167 TI - Capacitive micro pressure sensor integrated with a ring oscillator circuit on chip. AB - The study investigates a capacitive micro pressure sensor integrated with a ring oscillator circuit on a chip. The integrated capacitive pressure sensor is fabricated using the commercial CMOS (complementary metal oxide semiconductor) process and a post-process. The ring oscillator is employed to convert the capacitance of the pressure sensor into the frequency output. The pressure sensor consists of 16 sensing cells in parallel. Each sensing cell contains a top electrode and a lower electrode, and the top electrode is a sandwich membrane. The pressure sensor needs a post-CMOS process to release the membranes after completion of the CMOS process. The post-process uses etchants to etch the sacrificial layers, and to release the membranes. The advantages of the post process include easy execution and low cost. Experimental results reveal that the pressure sensor has a high sensitivity of 7 Hz/Pa in the pressure range of 0-300 kPa. PMID- 22303168 TI - New passive instruments developed for ocean monitoring at the remote sensing lab universitat politecnica de catalunya. AB - Lack of frequent and global observations from space is currently a limiting factor in many Earth Observation (EO) missions. Two potential techniques that have been proposed nowadays are: (1) the use of satellite constellations, and (2) the use of Global Navigation Satellite Signals (GNSS) as signals of opportunity (no transmitter required). Reflectometry using GNSS opportunity signals (GNSS-R) was originally proposed in 1993 by Martin-Neira (ESA-ESTEC) for altimetry applications, but later its use for wind speed determination has been proposed, and more recently to perform the sea state correction required in sea surface salinity retrievals by means of L-band microwave radiometry (T(B)). At present, two EO space-borne missions are currently planned to be launched in the near future: (1) ESA's SMOS mission, using a Y-shaped synthetic aperture radiometer, launch date November 2nd, 2009, and (2) NASA-CONAE AQUARIUS/SAC-D mission, using a three beam push-broom radiometer. In the SMOS mission, the multi-angle observation capabilities allow to simultaneously retrieve not only the surface salinity, but also the surface temperature and an "effective" wind speed that minimizes the differences between observations and models. In AQUARIUS, an L-band scatterometer measuring the radar backscatter (sigma(0)) will be used to perform the necessary sea state corrections. However, none of these approaches are fully satisfactory, since the effective wind speed captures some sea surface roughness effects, at the expense of introducing another variable to be retrieved, and on the other hand the plots (T(B)-sigma(0)) present a large scattering. In 2003, the Passive Advance Unit for ocean monitoring (PAU) project was proposed to the European Science Foundation in the frame of the EUropean Young Investigator Awards (EURYI) to test the feasibility of GNSS-R over the sea surface to make sea state measurements and perform the correction of the L-band brightness temperature. This paper: (1) provides an overview of the Physics of the L-band radiometric and GNSS reflectometric observations over the ocean, (2) describes the instrumentation that has been (is being) developed in the frame of the EURYI funded PAU project, (3) the ground-based measurements carried out so far, and their interpretation in view of placing a GNSS-reflectometer as secondary payload in future SMOS follow-on missions. PMID- 22303169 TI - Distance and cable length measurement system. AB - A simple, economic and successful design for distance and cable length detection is presented. The measurement system is based on the continuous repetition of a pulse that endlessly travels along the distance to be detected. There is a pulse repeater at both ends of the distance or cable to be measured. The endless repetition of the pulse generates a frequency that varies almost inversely with the distance to be measured. The resolution and distance or cable length range could be adjusted by varying the repetition time delay introduced at both ends and the measurement time. With this design a distance can be measured with centimeter resolution using electronic system with microsecond resolution, simplifying classical time of flight designs which require electronics with picosecond resolution. This design was also applied to position measurement. PMID- 22303170 TI - Numerical Analysis of Dynamic Effects of a Nonlinear Vibro-Impact Process for Enhancing the Reliability of Contact-Type MEMS Devices. AB - This paper reports on numerical modeling and simulation of a generalized contact type MEMS device having large potential in various micro-sensor/actuator applications, which are currently limited because of detrimental effects of the contact bounce phenomenon that is still not fully explained and requires comprehensive treatment. The proposed 2-D finite element model encompasses cantilever microstructures operating in a vacuum and impacting on a viscoelastic support. The presented numerical analysis focuses on the first three flexural vibration modes and their influence on dynamic characteristics. Simulation results demonstrate the possibility to use higher modes and their particular points for enhancing MEMS performance and reliability through reduction of vibro impact process duration. PMID- 22303171 TI - Sonar sensor models and their application to mobile robot localization. AB - This paper presents a novel approach to mobile robot localization using sonar sensors. This approach is based on the use of particle filters. Each particle is augmented with local environment information which is updated during the mission execution. An experimental characterization of the sonar sensors used is provided in the paper. A probabilistic measurement model that takes into account the sonar uncertainties is defined according to the experimental characterization. The experimental results quantitatively evaluate the presented approach and provide a comparison with other localization strategies based on both the sonar and the laser. Some qualitative results are also provided for visual inspection. PMID- 22303172 TI - A multi-agent system architecture for sensor networks. AB - The design of the control systems for sensor networks presents important challenges. Besides the traditional problems about how to process the sensor data to obtain the target information, engineers need to consider additional aspects such as the heterogeneity and high number of sensors, and the flexibility of these networks regarding topologies and the sensors in them. Although there are partial approaches for resolving these issues, their integration relies on ad hoc solutions requiring important development efforts. In order to provide an effective approach for this integration, this paper proposes an architecture based on the multi-agent system paradigm with a clear separation of concerns. The architecture considers sensors as devices used by an upper layer of manager agents. These agents are able to communicate and negotiate services to achieve the required functionality. Activities are organized according to roles related with the different aspects to integrate, mainly sensor management, data processing, communication and adaptation to changes in the available devices and their capabilities. This organization largely isolates and decouples the data management from the changing network, while encouraging reuse of solutions. The use of the architecture is facilitated by a specific modelling language developed through metamodelling. A case study concerning a generic distributed system for fire fighting illustrates the approach and the comparison with related work. PMID- 22303173 TI - Nonrigid Registration of Brain Tumor Resection MR Images Based on Joint Saliency Map and Keypoint Clustering. AB - This paper proposes a novel global-to-local nonrigid brain MR image registration to compensate for the brain shift and the unmatchable outliers caused by the tumor resection. The mutual information between the corresponding salient structures, which are enhanced by the joint saliency map (JSM), is maximized to achieve a global rigid registration of the two images. Being detected and clustered at the paired contiguous matching areas in the globally registered images, the paired pools of DoG keypoints in combination with the JSM provide a useful cluster-to-cluster correspondence to guide the local control-point correspondence detection and the outlier keypoint rejection. Lastly, a quasi inverse consistent deformation is smoothly approximated to locally register brain images through the mapping the clustered control points by compact support radial basis functions. The 2D implementation of the method can model the brain shift in brain tumor resection MR images, though the theory holds for the 3D case. PMID- 22303174 TI - Electrodynamics sensor for the image reconstruction process in an electrical charge tomography system. AB - Electrical charge tomography (EChT) is a non-invasive imaging technique that is aimed to reconstruct the image of materials being conveyed based on data measured by an electrodynamics sensor installed around the pipe. Image reconstruction in electrical charge tomography is vital and has not been widely studied before. Three methods have been introduced before, namely the linear back projection method, the filtered back projection method and the least square method. These methods normally face ill-posed problems and their solutions are unstable and inaccurate. In order to ensure the stability and accuracy, a special solution should be applied to obtain a meaningful image reconstruction result. In this paper, a new image reconstruction method - Least squares with regularization (LSR) will be introduced to reconstruct the image of material in a gravity mode conveyor pipeline for electrical charge tomography. Numerical analysis results based on simulation data indicated that this algorithm efficiently overcomes the numerical instability. The results show that the accuracy of the reconstruction images obtained using the proposed algorithm was enhanced and similar to the image captured by a CCD Camera. As a result, an efficient method for electrical charge tomography image reconstruction has been introduced. PMID- 22303175 TI - Field measurements and guidelines for the application of wireless sensor networks to the environment and security. AB - Frequently, Wireless Sensor Networks (WSN) are designed focusing on applications and omitting transmission problems in these wireless networks. In this paper, we present a measurement campaign that has been carried out using one of the most commonly used WSN platforms, the micaZ from Crossbow((c)). Based on these measurements, some guidelines to deploy a robust and reliable WSN are provided. The results are focused on security and environmental applications but can also be extrapolated to other scenarios. A main conclusion that can be extracted is that, from the transmission point of view, a dense WSN is one of the best choices to overcome many of the transmission problems such as the existence of a transitional region, redundance, forwarding, obstructions or interference with other systems. PMID- 22303176 TI - A 3D Sensor Based on a Profilometrical Approach. AB - An improved method which considers the use of Fourier and wavelet transform based analysis to infer and extract 3D information from an object by fringe projection on it is presented. This method requires a single image which contains a sinusoidal white light fringe pattern projected on it, and this pattern has a known spatial frequency and its information is used to avoid any discontinuities in the fringes with high frequency. Several computer simulations and experiments have been carried out to verify the analysis. The comparison between numerical simulations and experiments has proved the validity of this proposed method. PMID- 22303177 TI - Algorithmic error correction of impedance measuring sensors. AB - This paper describes novel design concepts and some advanced techniques proposed for increasing the accuracy of low cost impedance measuring devices without reduction of operational speed. The proposed structural method for algorithmic error correction and iterating correction method provide linearization of transfer functions of the measuring sensor and signal conditioning converter, which contribute the principal additive and relative measurement errors. Some measuring systems have been implemented in order to estimate in practice the performance of the proposed methods. Particularly, a measuring system for analysis of C-V, G-V characteristics has been designed and constructed. It has been tested during technological process control of charge-coupled device CCD manufacturing. The obtained results are discussed in order to define a reasonable range of applied methods, their utility, and performance. PMID- 22303179 TI - Flow injection chemiluminescent immunoassay for carcinoembryonic antigen using boronic immunoaffinity column. AB - A flow injection chemiluminescence immunoassay for rapid and sensitive detection of carcinoembryonic antigen (CEA) by using a phenylboronic acid-based immunoaffinity column as a glycoprotein collector was proposed in this paper. The column was prepared by coupling of 3-aminophenylboronic acid on the glass beads through a gamma-glycidoxypropyltrimethoxysilane (GPMS) linkage. Based on an indirect competitive immunoreaction, the mixture of CEA sample and enzyme conjugated CEA antibody (HRP-anti-CEA) was incubated in advance, followed by direct injection to the column to capture free HRP-labeled CEA antibody in the column. The trapped HRP-labeled antibody was detected by flow inject chemiluminescence in the presence of luminol and hydrogen peroxide. The decreased chemiluminescent signal was proportional to the concentration of CEA in the range of 3.0-30.0 ng/mL with a correlation coefficient of 0.998. The column showed an acceptable reproducibility and stability and is potentially used for practical clinical detection of the serum CEA level. PMID- 22303180 TI - A new experimental method for in situ corrosion monitoring under alternate wet dry conditions. AB - A new experimental method was applied in in situ corrosion monitoring of mild steel Q235 under alternate wet-dry conditions. The thickness of the electrolyte film during the wet cycle was monitored by a high-precision balance with a sensibility of 0.1 mg. At the same time, an electrochemical impedance technique was employed to study the effect of film thickness on corrosion rates. Experimental results showed that there was a critical electrolyte film condition for which the corrosion rate reached a maximum during wet-dry cycles. For the substrate, the critical condition could be described by a film thickness of about 17 MUm. For the rusted specimen, the critical condition could be described by an electrolyte amount of about 0.038 g, which is equivalent to a film thickness of 38 MUm. This monitoring system was very useful for studying atmospheric corrosion of metals covered by corrosion products. PMID- 22303178 TI - Aptamer-functionalized nano-biosensors. AB - Nanomaterials have become one of the most interesting sensing materials because of their unique size- and shape-dependent optical properties, high surface energy and surface-to-volume ratio, and tunable surface properties. Aptamers are oligonucleotides that can bind their target ligands with high affinity. The use of nanomaterials that are bioconjugated with aptamers for selective and sensitive detection of analytes such as small molecules, metal ions, proteins, and cells has been demonstrated. This review focuses on recent progress in the development of biosensors by integrating functional aptamers with different types of nanomaterials, including quantum dots, magnetic nanoparticles (NPs), metallic NPs, and carbon nanotubes. Colorimetry, fluorescence, electrochemistry, surface plasmon resonance, surface-enhanced Raman scattering, and magnetic resonance imaging are common detection modes for a broad range of analytes with high sensitivity and selectivity when using aptamer bioconjugated nanomaterials (Apt NMs). We highlight the important roles that the size and concentration of nanomaterials, the secondary structure and density of aptamers, and the multivalent interactions play in determining the specificity and sensitivity of the nanosensors towards analytes. Advantages and disadvantages of the Apt-NMs for bioapplications are focused. PMID- 22303181 TI - Novel absolute displacement sensor with wide range based on malus law. AB - The paper presents a novel wide range absolute displacement sensor based on polarized light detection principle. The sensor comprises of two sets of polarized light detecting systems which are coupled by pulleys. The inherent disadvantage in optic system like light source intensity drift is solved and absolute measurement with wide-range is achieved. A prototype and the relevant test bed have been built. The test results are in good agreement with expectation. Its measurement range is 540 mm, and its linearity is better than 0.05%. PMID- 22303182 TI - Perfluorinated plastic optical fiber tapers for evanescent wave sensing. AB - In this work we describe the fabrication and the characterization of perfluorinated plastic-cladded optical fiber tapers. The heat-and-pull procedure has been used to fabricate symmetric tapers. Devices with different taper ratio have been produced and the repeatability of the process has been verified. The very low refractive indexes of the core-cladding perfluorinated polymers (n = 1.35-1.34) permit a strong enhancement of the evanescent wave power fraction in aqueous environments (n = 1.33), making them very attractive for evanescent wave sensing. The tapers have been characterized carrying out evanescent field absorbance measurements with different concentrations of methylene blue in water and fluorescence collection measurements in an aqueous solution containing Cy5 dye. A good sensitivity, tightly related to the low refractive index of the core cladding materials and the geometrical profile, has been shown. PMID- 22303183 TI - Sensor for Distance Estimation Using FFT of Images. AB - In this paper, the problem of how to estimate the distance between an infrared emitter diode (IRED) and a camera from pixel grey-level intensities is examined from a practical standpoint. Magnitudes that affect grey level intensity were defined and related to the zero frequency component from the FFT image. A general model was also described and tested for distance estimation over the range from 420 to 800 cm using a differential methodology. Method accuracy is over 3%. PMID- 22303185 TI - A cluster-based architecture to structure the topology of parallel wireless sensor networks. AB - A wireless sensor network is a self-configuring network of mobile nodes connected by wireless links where the nodes have limited capacity and energy. In many cases, the application environment requires the design of an exclusive network topology for a particular case. Cluster-based network developments and proposals in existence have been designed to build a network for just one type of node, where all nodes can communicate with any other nodes in their coverage area. Let us suppose a set of clusters of sensor nodes where each cluster is formed by different types of nodes (e.g., they could be classified by the sensed parameter using different transmitting interfaces, by the node profile or by the type of device: laptops, PDAs, sensor etc.) and exclusive networks, as virtual networks, are needed with the same type of sensed data, or the same type of devices, or even the same type of profiles. In this paper, we propose an algorithm that is able to structure the topology of different wireless sensor networks to coexist in the same environment. It allows control and management of the topology of each network. The architecture operation and the protocol messages will be described. Measurements from a real test-bench will show that the designed protocol has low bandwidth consumption and also demonstrates the viability and the scalability of the proposed architecture. Our ccluster-based algorithm is compared with other algorithms reported in the literature in terms of architecture and protocol measurements. PMID- 22303184 TI - Laser spectroscopy for atmospheric and environmental sensing. AB - Lasers and laser spectroscopic techniques have been extensively used in several applications since their advent, and the subject has been reviewed extensively in the last several decades. This review is focused on three areas of laser spectroscopic applications in atmospheric and environmental sensing; namely laser induced fluorescence (LIF), cavity ring-down spectroscopy (CRDS), and photoluminescence (PL) techniques used in the detection of solids, liquids, aerosols, trace gases, and volatile organic compounds (VOCs). PMID- 22303186 TI - Mood, Weight, and Physical Activity Among Obese Individuals Enrolled In a Long term Weight-loss Program: Trajectories and Associations with Gender. AB - OBJECTIVE: To examine the trajectories of mood, weight and physical activity, and associations between mood, weight, and gender, among 213 obese individuals. METHODS: Prospective, longitudinal design. Assessments at baseline and 6, 12, and 18 months of Profile of Mood States, Paffenbarger Physical Activity Questionnaire, and weight. RESULTS: Total mood disturbance decreased from baseline to 6 months, with no change thereafter. Weight decreased from baseline to 6 to 12 months, and increased from 12 to 18 months. Physical activity increased from baseline to 6 months, and 12 to 18 months. Increased physical activity predicted greater vigor and less fatigue over time. Females high in distress at 6 months lost less weight than females low in distress and at 18 months gained more weight than those low in distress. There were no such associations among males. CONCLUSION: The trajectories of mood, weight and physical activity were synchronous only in the short-term. Distress monitoring, targeted to females who relapse, may be warranted. PMID- 22303187 TI - Taxonomy and phylogeny of Arabidopsis (brassicaceae). AB - Detailed taxonomic, cytological, and phylogenetic accounts of Arabidopsis are presented. As currently delimited, the genus consists of nine species all of which are indigenous to Europe, with the ranges of two species extending into northern and eastern Asia and North American into central United States. A survey of chromosome numbers in the genus is presented, and the country of origin for each count is given. Detailed descriptions of all species and subspecies and keys to all taxa are provided. Generic assignments are updated for the 50 species previously included in Arabidopsis. A cladogram of the species of Arabidopsis based on molecular phylogenetic studies by the authors is given. PMID- 22303188 TI - Ecology and evolutionary biology of Arabidopsis. AB - Arabidopsis thaliana is now widely used as a model system in molecular and developmental biology, as well as in physiology and cell biology. However, ecologists and evolutionary biologists have turned their attention to the mouse ear cress only much more recently and almost reluctantly. The reason for this is the perception that A. thaliana is not particularly interesting ecologically and that it represents an oddity from an evolutionary standpoint. While there is some truth in both these attitudes, similar criticisms apply to other model systems such as the fruit fly Drosophila melanogaster, which has been extensively studied from an organismal perspective. Furthermore, the shortcomings of A. thaliana in terms of its restricted ecological niche are counterbalanced by the wealth of information on the molecular and developmental biology of this species, which makes possible to address evolutionary questions that can rarely be pursued in other species. This chapter reviews the history of the use of A. thaliana in organismal biology and discusses some of the recent work and future perspectives of research on a variety of field including life history evolution, phenotypic plasticity, natural selection and quantitative genetics. I suggest that the future of both molecular and especially organismal biology lies into expanding our knowledge from limited and idiosyncratic model systems to their phylogenetic neighborhood, which is bound to be more varied and biologically interesting. PMID- 22303189 TI - Sterol metabolism. PMID- 22303190 TI - Repair of damaged bases. PMID- 22303191 TI - Brassinosteroids. PMID- 22303192 TI - Molecular and developmental biology of inorganic nitrogen nutrition. PMID- 22303193 TI - The oxylipin pathway in Arabidopsis. AB - Oxylipins are acyclic or cyclic oxidation products derived from the catabolism of fatty acids which regulate many defense and developmental pathways in plants. The dramatic increase in the volume of publications and reviews on these compounds since 1997 documents the increasing interest in this compound and its role in plants. Research on this topic has solidified our understanding of the chemistry and biosynthetic pathways for oxylipin production. However, more information is still needed on how free fatty acids are produced and the role of beta-oxidation in the biosynthetic pathway for oxylipins. It is also becoming apparent that oxylipin content and composition changes during growth and development and during pathogen or insect attack. Oxylipins such as jasmonic acid (JA) or 12-oxo phytodienoic acid modulate the expression of numerous genes and influence specific aspects of plant growth, development and responses to abiotic and biotic stresses. Although oxylipins are believed to act alone, several examples were presented to illustrate that JA-induced responses are modulated by the type and the nature of crosstalk with other signaling molecules such as ethylene and salicylic acid. How oxylipins cause changes in gene expression and instigate a physiological response is becoming understood with the isolation of mutations in both positive and negative regulators in the jasmonate signaling pathway and the use of cDNA microarrays. PMID- 22303194 TI - Cuticular waxes of Arabidopsis. PMID- 22303195 TI - Sulfate metabolism. PMID- 22303196 TI - Purine and pyrimidine nucleotide synthesis and metabolism. PMID- 22303197 TI - Storage proteins. AB - Plants accumulate storage substances such as starch, lipids and proteins in certain phases of development. Storage proteins accumulate in both vegetative and reproductive tissues and serve as a reservoir to be used in later stages of plant development. The accumulation of storage protein is thus beneficial for the survival of plants. Storage proteins are also an important source of dietary plant proteins. Here, we summarize the genome organization and regulation of gene expression of storage protein genes in Arabidopsis. PMID- 22303198 TI - The biopolymers cutin and suberin. PMID- 22303199 TI - ArabidopsisChitinases: a Genomic Survey. AB - Plant chitinases (EC 3.2.1.14) belong to relatively large gene families subdivided in classes that suggest class-specific functions. They are commonly induced upon the attack of pathogens and by various sources of stress, which led to associating them with plant defense in general. However, it is becoming apparent that most of them display several functions during the plant life cycle, including taking part in developmental processes such as pollination and embryo development. The number of chitinases combined with their multiple functions has been an obstacle to a better understanding of their role in plants. It is therefore important to identify and inventory all chitinase genes of a plant species to be able to dissect their function and understand the relations between the different classes. Complete sequencing of the Arabidopsis genome has made this task feasible and we present here a survey of all putative chitinase encoding genes accompanied by a detailed analysis of their sequence. Based on their characteristics and on studies on other plant chitinases, we propose an overview of their possible functions as well as modified annotations for some of them. PMID- 22303201 TI - Molecular Genetics of Non-processive Glycosyltransferases. PMID- 22303200 TI - Phosphate transport and homeostasis in Arabidopsis. PMID- 22303202 TI - Cytochromes p450. AB - There are 272 cytochrome P450 genes (including 26 pseudogenes) in the Arabidopsis genome. P450s thus form one of the largest families of proteins in higher plants. This explosion of the P450 family is thought to have occurred via gene duplication and conversion, and to result from the need of sessile plants to adapt to a harsh environment and to protect themselves from pathogens and predators. P450s sometimes share less than 20% identity and catalyze extremely diverse reactions. Their biological functions range from the synthesis of structural macromolecules such as lignin, cutin or suberin, to the synthesis or catabolism of all types of hormone or signaling molecules, the synthesis of pigments and defense compounds, and to the metabolism of xenobiotics. In despite of a huge acceleration in our understanding of plant P450 functions in the recent years, the vast majority of these functions remain completely unknown. PMID- 22303203 TI - Interactions Between Xanthomonas Species and Arabidopsis thaliana. AB - Arabidopsis has been well studied as a model plant for plant pathogen interactions. While a large portion of the literature has been devoted to interactions between Arabidopsis and Pseudomonas and Peronospora species, a small cadre of researchers have been making inroads on the response of Arabidopsis to Xanthomonas. Differential responses of Arabidopsis accessions to isolates of Xanthomonas campestris pv campestris include tolerance, a hypersensitive response, resistance without a hypersensitive response and disease which is characterized by chlorosis and necrosis. Loci that govern the recognition of X. c. campestris have been identified and are the focus of on-going positional cloning efforts. Signaling and other downstream molecules involved in manifestation of resistance to Xanthomonas have been investigated resulting in the identification of many components of the resistance response. Parallel to the characterization of the host response, molecular and genomic efforts focused on the pathogen have the potential to reveal the mechanisms by which this bacterium can invade and colonize host tissues. ABBREVIATIONS: colony forming units (CFU), Columbia (Col-0), days post inoculation (dpi), hypersensitive response (HR), Landsberg erecta (Ler), pathogenesis-related protein 1 (PR-1), phenylalanine ammonia lyase (PAL), Xanthomonas campestris pv campestris (Xcc). PMID- 22303205 TI - The Use of Arabidopsis to Study Interactions between Parasitic Angiosperms and Their Plant Hosts. AB - Parasitic plants invade host plants in order to rob them of water, minerals and nutrients. The consequences to the infected hosts can be debilitating and some of the world's most pernicious agricultural weeds are parasitic. Parasitic genera of the Scrophulariaceae and Orobanchaceae directly invade roots of neighboring plants via underground structures called haustoria. The mechanisms by which these parasites identify and associate with host plants present unsurpassed opportunities for studying chemical signaling in plant-plant interactions. Seeds of some parasites require specific host factors for efficient germination, thereby insuring the availability of an appropriate host root prior to germination. A second set of signal molecules is required to induce haustorium development and the beginning of heterotrophy. Later stages in parasitism also require the presence of host factors, although these have not yet been well characterized. Arabidopsis is being used as a model host plant to identify genetic loci associated with stimulating parasite germination, haustorium development, and parasite support. Arabidopsis is also being employed to explore how host plants respond to parasite attack. Current methodologies and recent findings in Arabidopsis - parasitic plant interactions will be discussed. PMID- 22303204 TI - Arabidopsis and the genetic potential for the phytoremediation of toxic elemental and organic pollutants. AB - In a process called phytoremediation, plants can be used to extract, detoxify, and/or sequester toxic pollutants from soil, water, and air. Phytoremediation may become an essential tool in cleaning the environment and reducing human and animal exposure to potential carcinogens and other toxins. Arabidopsis has provided useful information about the genetic, physiological, and biochemical mechanisms behind phytoremediation, and it is an excellent model genetic organism to test foreign gene expression. This review focuses on Arabidopsis studies concerning: 1) the remediation of elemental pollutants; 2) the remediation of organic pollutants; and 3) the phytoremediation genome. Elemental pollutants include heavy metals and metalloids (e.g., mercury, lead, cadmium, arsenic) that are immutable. The general goal of phytoremediation is to extract, detoxify, and hyperaccumulate elemental pollutants in above-ground plant tissues for later harvest. A few dozen Arabidopsis genes and proteins that play direct roles in the remediation of elemental pollutants are discussed. Organic pollutants include toxic chemicals such as benzene, benzo(a)pyrene, polychlorinated biphenyls, trichloroethylene, trinitrotoluene, and dichlorodiphenyltrichloroethane. Phytoremediation of organic pollutants is focused on their complete mineralization to harmless products, however, less is known about the potential of plants to act on complex organic chemicals. A preliminary survey of the Arabidopsis genome suggests that as many as 700 genes encode proteins that have the capacity to act directly on environmental pollutants or could be modified to do so. The potential of the phytoremediation proteome to be used to reduce human exposure to toxic pollutants appears to be enormous and untapped. PMID- 22303206 TI - Oxidative stress and acclimation mechanisms in plants. PMID- 22303207 TI - The Arabidopsis thaliana-pseudomonas syringae interaction. PMID- 22303208 TI - Arabidopsis thaliana: A Model for the Study of Root and Shoot Gravitropism. AB - For most plants, shoots grow upward and roots grow downward. These growth patterns illustrate the ability for plant organs to guide their growth at a specified angle from the gravity vector (gravitropism). They allow shoots to grow upward toward light, where they can photosynthesize, and roots to grow downward into the soil, where they can anchor the plant as well as take up water and mineral ions.Gravitropism involves several steps organized in a specific response pathway. These include the perception of a gravistimulus (reorientation within the gravity field), the transduction of this mechanical stimulus into a physiological signal, the transmission of this signal from the site of sensing to the site of response, and a curvature-response which allows the organ tip to resume growth at a predefined set angle from the gravity vector.The primary sites for gravity sensing are located in the cap for roots, and in the endodermis for shoots. The curvature response occurs in the elongation zones for each organ. Upon gravistimulation, a gradient of auxin appears to be generated across the stimulated organ, and be transmitted to the site of response where it promotes a differential growth response. Therefore, while the gravity-induced auxin gradient has to be transmitted from the cap to the elongation zones in roots, there is no need for a longitudinal transport in shoots, as sites for gravity sensing and response overlap in this organ.A combination of molecular genetics, physiology, biochemistry and cell biology, coupled with the utilization of Arabidopsis thaliana as a model system, have recently allowed the identification of a number of molecules involved in the regulation of each phase of gravitropism in shoots and roots of higher plants. In this review, we attempt to summarize the results of these experiments, and we conclude by comparing the molecular and physiological mechanisms that underlie gravitropism in these organs. ABBREVIATIONS: GSPA: gravitational set point angle; IAA: indole-3-acetic acid; NAA: 1-naphthalene acetic acid; NPA: 1-N-naphthylphthalamic acid; 2,4-D: 2,4 dichlorphenoxy acetic acid; TIBA: 2,3,5-triiodobenzoic acid. PMID- 22303209 TI - The Arabidopsis circadian system. AB - Rhythms with periods of approximately 24 hr are widespread in nature. Those that persist in constant conditions are termed circadian rhythms and reflect the activity of an endogenous biological clock. Plants, including Arabidopsis, are richly rhythmic. Expression analysis, most recently on a genomic scale, indicates that the Arabidopsis circadian clock regulates a number of key metabolic pathways and stress responses. A number of sensitive and high-throughput assays have been developed to monitor the Arabidopsis clock. These assays have facilitated the identification of components of plant circadian systems through genetic and molecular biological studies. Although much remains to be learned, the framework of the Arabidopsis circadian system is coming into focus.DedicationThis review is dedicated to the memory of DeLill Nasser, a wonderful mentor and an unwavering advocate of both Arabidopsis and circadian rhythms research. PMID- 22303210 TI - Salt tolerance. AB - Studying salt stress is an important means to the understanding of plant ion homeostasis and osmo-balance. Salt stress research also benefits agriculture because soil salinity significantly limits plant productivity on agricultural lands. Decades of physiological and molecular studies have generated a large body of literature regarding potential salt tolerance determinants. Recent advances in applying molecular genetic analysis and genomics tools in the model plant Arabidopsis thaliana are shading light on the molecular nature of salt tolerance effectors and regulatory pathways. PMID- 22303211 TI - Photomorphogenesis. PMID- 22303213 TI - Root hairs. PMID- 22303214 TI - Cytokinins. PMID- 22303212 TI - Abscisic Acid biosynthesis and response. PMID- 22303215 TI - Stomatal development in Arabidopsis. AB - Stomata consist of two guard cells around a pore and act as turgor-operated valves for gas exchange. Arabidopsis stomata develop from one or more asymmetric divisions followed by the symmetric division of the guard mother cell. Stomatal number is partly a function of the availability of smaller epidermal cells that are competent to divide asymmetrically. Stomata are spaced apart from each other by at least one neighbor cell. Pattern generation may involve cell-cell signaling that transmits spatial cues used to orient specific classes of asymmetric divisions. TOO MANY MOUTHS may function in receiving or transducing these cues to orient asymmetric divisions. TMM also is a negative or positive regulator of entry into the stomatal pathway, with the direction of the response dependent on organ and location. STOMATAL DENSITY AND DISTRIBUTION1 is a negative regulator of stomatal formation throughout the shoot and encodes a processing protease that may function in intercellular communication. FOUR LIPS apparently controls the number symmetric divisions at the guard mother cell stage. In some organs, such as the hypocotyl, the placement of stomata may be coordinated with internal features and involves genes that also regulate root hair and trichome formation. Other mutations affect guard cell morphogenesis, cytokinesis, and stomatal number in response to carbon dioxide concentration. The molecular analysis of stomatal development promises advances in understanding intercellular signaling, the control of the plane and polarity of asymmetric division, the specification of cell fate, and the regulation of cell differentiation and shape. PMID- 22303216 TI - Ethylene. PMID- 22303217 TI - Leaf development. AB - The shoot system is the basic unit of development of seed plants and is composed of a leaf, a stem, and a lateral bud that differentiates into a lateral shoot. The most specialized organ in angiosperms, the flower, can be considered to be part of the same shoot system since floral organs, such as the sepal, petal, stamen, and carpel, are all modified leaves. Scales, bracts, and certain kinds of needle are also derived from leaves. Thus, an understanding of leaf development is critical to an understanding of shoot development. Moreover, leaves play important roles in photosynthesis, respiration and photoperception. Thus, a full understanding of leaves is directly related to a full understanding of seed plants.The details of leaf development remain unclear. The difficulties encountered in studies of leaf development, in particular in dicotyledonous plants such as Arabidopsis thaliana (L.) Henyn., are derived from the complex process of leaf development, during which the division and elongation of cells occur at the same time and in the same region of the leaf primordium (Maksymowych, 1963; Poethig and Sussex, 1985). Thus, we cannot divide the entire process into unit processes in accordance with the tenets of classical anatomy.Genetic approaches in Arabidopsis, a model plant (Meyerowitz and Pruitt, 1985), have provided a powerful tool for studies of mechanisms of leaf development in dicotyledonous plants, and various aspects of the mechanisms that control leaf development have been revealed in recent developmental and molecular genetic studies of Arabidopsis (for reviews, see Tsukaya, 1995 and 1998; Van Lijsebettens and Clarke, 1998; Sinha, 1999; Van Volkenburgh, 1999; Tsukaya, 2000; Byrne et al., 2001; Dengler and Kang, 2001; Dengler and Tsukaya, 2001; Tsukaya, 2001). In this review, we shall examine the information that is currently available about various mechanisms of leaf development in Arabidopsis. Vascular patterning is also an important factor in the determination of leaf shape, and this topic is reviewed in this resource by Turner (see also Dengler and Kang, 2001). The interested reader is also referred to work on the basic characterization of the vascular patterning in foliage leaves of Arabidopsis has been carried out by Candela et al. (1999) and Semiarti et al. (2001). For terminology, see (Fig. 1). PMID- 22303218 TI - Arabidopsis variegation mutants. PMID- 22303219 TI - Transcription and tyranny in the nucleolus: the organization, activation, dominance and repression of ribosomal RNA genes. PMID- 22303222 TI - Root development. PMID- 22303220 TI - Transcriptional regulation: a genomic overview. AB - The availability of the Arabidopsis thaliana genome sequence allows a comprehensive analysis of transcriptional regulation in plants using novel genomic approaches and methodologies. Such a genomic view of transcription first necessitates the compilation of lists of elements. Transcription factors are the most numerous of the different types of proteins involved in transcription in eukaryotes, and the Arabidopsis genome codes for more than 1,500 of them, or approximately 6% of its total number of genes. A genome-wide comparison of transcription factors across the three eukaryotic kingdoms reveals the evolutionary generation of diversity in the components of the regulatory machinery of transcription. However, as illustrated by Arabidopsis, transcription in plants follows similar basic principles and logic to those in animals and fungi. A global view and understanding of transcription at a cellular and organismal level requires the characterization of the Arabidopsis transcriptome and promoterome, as well as of the interactome, the localizome, and the phenome of the proteins involved in transcription. PMID- 22303221 TI - Genes and proteins for solute transport and sensing. PMID- 22303223 TI - Primary N-assimilation into Amino Acids in Arabidopsis. PMID- 22303224 TI - Vascular patterning. PMID- 22303225 TI - The Arabidopsis cytoskeletal genome. AB - In the past decade the first Arabidopsis genes encoding cytoskeletal proteins were identified. A few dozen genes in the actin and tubulin cytoskeletal systems have been characterized thoroughly, including gene families encoding actins, profilins, actin depolymerizing factors, alpha-tubulins, and beta-tubulins. Conventional molecular genetics have shown these family members to be differentially expressed at the temporal and spatial levels with an ancient split separating those genes expressed in vegetative tissues from those expressed in reproductive tissues. A few members of other cytoskeletal gene families have also been partially characterized, including an actin-related protein, annexins, fimbrins, kinesins, myosins, and villins. In the year 2001 the Arabidopsis genome sequence was completed. Based on sequence homology with well-characterized animal, fungal, and protist sequences, we find candidate cytoskeletal genes in the Arabidopsis database: more than 150 actin-binding proteins (ABPs), including monomer binding, capping, cross-linking, attachment, and motor proteins; more than 200 microtubule-associated proteins (MAPs); and, surprisingly, 10 to 40 potential intermediate filament (IF) proteins. Most of these sequences are uncharacterized and were not identified as related to cytoskeletal proteins. Several Arabidopsis ABPs, MAPs, and IF proteins are represented by individual genes and most were represented as as small gene families. However, several classes of cytoskeletal genes including myosin, eEF1alpha, CLIP, tea1, and kinesin are part of large gene families with 20 to 70 potential gene members each. This treasure trove of data provides an unprecedented opportunity to make rapid advances in understanding the complex plant cytoskeletal proteome. However, the functional analysis of these proposed cytoskeletal proteins and their mutants will require detailed analysis at the cell biological, molecular genetic, and biochemical levels. New approaches will be needed to move more efficiently and rapidly from this mass of DNA sequence to functional studies on cytoskeletal proteins. PMID- 22303226 TI - Phytochrome signaling mechanism. PMID- 22303227 TI - Fruit development in Arabidopsis. PMID- 22303229 TI - Storage reserve mobilisation and seedling establishment in Arabidopsis. PMID- 22303228 TI - A molecular portrait of Arabidopsis meiosis. AB - Meiosis is essential for eukaryotic sexual reproduction and important for genetic diversity among individuals. Efforts during the last decade in Arabidopsis have greatly expanded our understanding of the molecular basis of plant meiosis, which has traditionally provided much information about the cytological description of meiosis. Through both forward genetic analysis of mutants with reduced fertility and reverse genetic studies of homologs of known meiotic genes, we now have a basic knowledge about genes important for meiotic recombination and its relationship to pairing and synapsis, critical processes that ensure proper homolog segregation. In addition, several genes affecting meiotic progression, spindle assembly, chromosome separation, and meiotic cytokinesis have also been uncovered and characterized. It is worth noting that Arabidopsis molecular genetic studies are also revealing secrets of meiosis that have not yet been recognized elsewhere among eukaryotes, including gene functions that might be unique to plants and those that are potentially shared with animals and fungi. As we enter the post-genomics era of plant biology, there is no doubt that the next ten years will see an even greater number of discoveries in this important area of plant development and cell biology. ABBREVIATIONS: DAPI, 4',6-diamidino-2 phenylindole; DSB, double strand break; DSBR, double strand break repair; SC, synaptonemal complex; TEM, transmission electron microscopy. PMID- 22303231 TI - Arabidopsis-insect interactions. PMID- 22303230 TI - The Protein Phosphatases and Protein Kinases of Arabidopsis thaliana. PMID- 22303232 TI - Polar auxin transport and asymmetric auxin distribution. PMID- 22303233 TI - DNA methylation and demethylation in Arabidopsis. PMID- 22303234 TI - Gibberellin metabolism, perception and signaling pathways in Arabidopsis. AB - Bioactive gibberellins (GAs) are diterpene phytohormones that modulate growth and development throughout the whole life cycle of the plant. Arabidopsis genes encoding most GA biosynthesis and catabolism enzymes, as well as GA receptors (GIBBERELLIN INSENSITIVE DWARF1, GID1) and early GA signaling components have been identified. Expression studies on the GA biosynthesis genes are beginning to reveal the potential sites of GA biosynthesis during plant development. Biochemical and genetic analyses demonstrate that GA de-represses its signaling pathway by binding to GID1s, which induce degradation of GA signaling repressors (DELLAs) via an ubiquitin-proteasome pathway. To modulate plant growth and development, the GA pathway is also regulated by endogenous signals (other hormones) and environmental cues (such as light, temperature and salt stress). In many cases, these internal and external cues directly affect GA metabolism and bioactive GA levels, and indirectly alter DELLA accumulation and GA responses. Importantly, direct negative interaction between DELLA and PIF3 and PIF4 (2 phytochrome interacting transcription factors) appears to integrate the effects of light and GA on hypocotyl elongation. PMID- 22303235 TI - Chloroplast biogenesis: control of plastid development, protein import, division and inheritance. AB - The chloroplast is a multi-copy cellular organelle that not only performs photosynthesis but also synthesizes amino acids, lipids and phytohormones. The plastid also responds to environmental stimuli such as gravitropism. Biogenesis of chloroplasts is initiated from proplastids in shoot meristems, and involves a series of important events. In the last decade, considerable progress has been made towards understanding various aspects of chloroplast biogenesis at the molecular level, via studies in model systems such as Arabidopsis. This review focuses on two important aspects of chloroplast biogenesis, synthesis/assembly and division/transmission. Chloroplasts originated through endosymbiosis from an ancestor of extant cyanobacteria, and thus contain their own genomes. DNA in chloroplasts is organized into complexes with proteins, and these are called nucleoids. The synthesis of chloroplast proteins is regulated at various steps. However, a majority of proteins are synthesized in the cytosol, and their proper import into chloroplast compartments is a prerequisite for chloroplast development. Fundamental aspects of plastid gene expression/regulation and chloroplast protein transport are described, together with recent proteome analyses of the organelle. Chloroplasts are not de novo synthesized, but instead are propagated from pre-existing plastids. In addition, plastids are transmitted from generation to generation with a unique mode of inheritance. Our current knowledge on the division machinery and the inheritance of plastids is described. PMID- 22303237 TI - Two-component signaling elements and histidyl-aspartyl phosphorelays. AB - Two-component systems are an evolutionarily ancient means for signal transduction. These systems are comprised of a number of distinct elements, namely histidine kinases, response regulators, and in the case of multi-step phosphorelays, histidine-containing phosphotransfer proteins (HPts). Arabidopsis makes use of a two-component signaling system to mediate the response to the plant hormone cytokinin. Two-component signaling elements have also been implicated in plant responses to ethylene, abiotic stresses, and red light, and in regulating various aspects of plant growth and development. Here we present an overview of the two-component signaling elements found in Arabidopsis, including functional and phylogenetic information on both bona-fide and divergent elements. PMID- 22303236 TI - Mitochondrial biogenesis and function in Arabidopsis. AB - Mitochondria represent the powerhouse of cells through their synthesis of ATP. However, understanding the role of mitochondria in the growth and development of plants will rely on a much deeper appreciation of the complexity of this organelle. Arabidopsis research has provided clear identification of mitochondrial components, allowed wide-scale analysis of gene expression, and has aided reverse genetic manipulation to test the impact of mitochondrial component loss on plant function. Forward genetics in Arabidopsis has identified mitochondrial involvement in mutations with notable impacts on plant metabolism, growth and development. Here we consider the evidence for components involved in mitochondria biogenesis, metabolism and signalling to the nucleus. PMID- 22303238 TI - Storage reserve accumulation in Arabidopsis: metabolic and developmental control of seed filling. AB - In the life cycle of higher plants, seed development is a key process connecting two distinct sporophytic generations. Seed development can be divided into embryo morphogenesis and seed maturation. An essential metabolic function of maturing seeds is the deposition of storage compounds that are mobilised to fuel post germinative seedling growth. Given the importance of seeds for food and animal feed and considering the tremendous interest in using seed storage products as sustainable industrial feedstocks to replace diminishing fossil reserves, understanding the metabolic and developmental control of seed filling constitutes a major focus of plant research. Arabidopsis thaliana is an oilseed species closely related to the agronomically important Brassica oilseed crops. The main storage compounds accumulated in seeds of A. thaliana consist of oil stored as triacylglycerols (TAGs) and seed storage proteins (SSPs). Extensive tools developed for the molecular dissection of A. thaliana development and metabolism together with analytical and cytological procedures adapted for very small seeds have led to a good description of the biochemical pathways producing storage compounds. In recent years, studies using these tools have shed new light on the intricate regulatory network controlling the seed maturation process. This network involves sugar and hormone signalling together with a set of developmentally regulated transcription factors. Although much remains to be elucidated, the framework of the regulatory system controlling seed filling is coming into focus. PMID- 22303239 TI - The Clickable Guard Cell, Version II: Interactive Model of Guard Cell Signal Transduction Mechanisms and Pathways. AB - Guard cells are located in the leaf epidermis and pairs of guard cells surround and form stomatal pores, which regulate CO(2) influx from the atmosphere into leaves for photosynthetic carbon fixation. Stomatal guard cells also regulate water loss of plants via transpiration to the atmosphere. Signal transduction mechanisms in guard cells integrate a multitude of different stimuli to modulate stomatal apertures. Stomata open in response to light. Stomata close in response to drought stress, elevated CO(2), ozone and low humidity. In response to drought, plants synthesize the hormone abscisic acid (ABA) that triggers closing of stomatal pores. Guard cells have become a highly developed model system for dissecting signal transduction mechanisms in plants and for elucidating how individual signaling mechanisms can interact within a network in a single cell. Many new findings have been made in the last few years. This chapter is an update of an electronic interactive chapter in the previous edition of The Arabidopsis Book (Maser et al. 2003). Here we focus on mechanisms for which genes and mutations have been characterized, including signaling components for which there is substantial signaling, biochemical and genetic evidence. Ion channels have been shown to represent targets of early signal transduction mechanisms and provide functional signaling and quantitative analysis points to determine where and how mutations affect branches within the guard cell signaling network. Although a substantial number of genes and proteins that function in guard cell signaling have been identified in recent years, there are many more left to be identified and the protein-protein interactions within this network will be an important subject of future research. A fully interactive clickable electronic version of this publication can be accessed at the following web site: http://www biology.ucsd.edu/labs/schroeder/clickablegc2/. The interactive clickable version includes the following features: Figure 1. Model for the roles of ion channels in ABA signaling.Figure 2. Blue light signaling pathways in guard cells.Figure 3. ABA signaling pathways in guard cells.Figure 1 is linked to explanations that appear upon mouse-over. Figure 2 and Figure 3 are clickable and linked to info boxes, which in turn are linked to TAIR, to relevant abstracts in PubMed, and to updated background explanations from Schroeder et al (2001), used with permission of Annual Reviews of Plant Biology. PMID- 22303240 TI - The Powdery Mildew Disease of Arabidopsis: A Paradigm for the Interaction between Plants and Biotrophic Fungi. AB - The powdery mildew diseases, caused by fungal species of the Erysiphales, have an important economic impact on a variety of plant species and have driven basic and applied research efforts in the field of phytopathology for many years. Although the first taxonomic reports on the Erysiphales date back to the 1850's, advances into the molecular biology of these fungal species have been hampered by their obligate biotrophic nature and difficulties associated with their cultivation and genetic manipulation in the laboratory. The discovery in the 1990's of a few species of powdery mildew fungi that cause disease on Arabidopsis has opened a new chapter in this research field. The great advantages of working with a model plant species have translated into remarkable progress in our understanding of these complex pathogens and their interaction with the plant host. Herein we summarize advances in the study of Arabidopsis-powdery mildew interactions and discuss their implications for the general field of plant pathology. We provide an overview of the life cycle of the pathogens on Arabidopsis and describe the structural and functional changes that occur during infection in the host and fungus in compatible and incompatible interactions, with special emphasis on defense signaling, resistance pathways, and compatibility factors. Finally, we discuss the future of powdery mildew research in anticipation of the sequencing of multiple powdery mildew genomes. The cumulative body of knowledge on powdery mildews of Arabidopsis provides a valuable tool for the study and understanding of disease associated with many other obligate biotrophic pathogen species. PMID- 22303241 TI - The secretory system of Arabidopsis. AB - Over the past few years, a vast amount of research has illuminated the workings of the secretory system of eukaryotic cells. The bulk of this work has been focused on the yeast Saccharomyces cerevisiae, or on mammalian cells. At a superficial level, plants are typical eukaryotes with respect to the operation of the secretory system; however, important differences emerge in the function and appearance of endomembrane organelles. In particular, the plant secretory system has specialized in several ways to support the synthesis of many components of the complex cell wall, and specialized kinds of vacuole have taken on a protein storage role-a role that is intended to support the growing seedling, but has been co-opted to support human life in the seeds of many crop plants. In the past, most research on the plant secretory system has been guided by results in mammalian or fungal systems but recently plants have begun to stand on their own as models for understanding complex trafficking events within the eukaryotic endomembrane system. PMID- 22303243 TI - Web-based Arabidopsis functional and structural genomics resources. AB - As plant research moves to a "post-genomic" era, many diverse internet resources become available to the international research community. Arabidopsis thaliana, because of its small size, rapid life cycle and simple genome, has been a model system for decades, with much research funding and many projects devoted to creation of functional and structural genomics resources. Different types of data, including genome, transcriptome, proteome, phenome, metabolome and ionome are stored in these resources. In this chapter, a variety of genomics resources are introduced, with simple descriptions of how some can be accessed by laboratory researchers via the internet. PMID- 22303242 TI - Sugar sensing and signaling. AB - Plants, restricted by their environment, need to integrate a wide variety of stimuli with their metabolic activity, growth and development. Sugars, generated by photosynthetic carbon fixation, are central in coordinating metabolic fluxes in response to the changing environment and in providing cells and tissues with the necessary energy for continued growth and survival. A complex network of metabolic and hormone signaling pathways are intimately linked to diverse sugar responses. A combination of genetic, cellular and systems analyses have uncovered nuclear HXK1 (hexokinase1) as a pivotal and conserved glucose sensor, directly mediating transcription regulation, while the KIN10/11 energy sensor protein kinases function as master regulators of transcription networks under sugar and energy deprivation conditions. The involvement of disaccharide signals in the regulation of specific cellular processes and the potential role of cell surface receptors in mediating sugar signals add to the complexity. This chapter gives an overview of our current insight in the sugar sensing and signaling network and describes some of the molecular mechanisms involved. PMID- 22303244 TI - Seed dormancy and germination. AB - Seed dormancy allows seeds to overcome periods that are unfavourable for seedling established and is therefore important for plant ecology and agriculture. Several processes are known to be involved in the induction of dormancy and in the switch from the dormant to the germinating state. The role of plant hormones, the different tissues and genes involved, including newly identified genes in dormancy and germination are described in this chapter, as well as the use transcriptome, proteome and metabolome analyses to study these mechanistically not well understood processes. PMID- 22303245 TI - Powerful partners: Arabidopsis and chemical genomics. AB - Chemical genomics (i.e. genomics scale chemical genetics) approaches capitalize on the ability of low molecular mass molecules to modify biological processes. Such molecules are used to modify the activity of a protein or a pathway in a manner that it is tunable and reversible. Bioactive chemicals resulting from forward or reverse chemical screens can be useful in understanding and dissecting complex biological processes due to the essentially limitless variation in structure and activities inherent in chemical space. A major advantage of this approach as a powerful addition to conventional plant genetics is the fact that chemical genomics can address loss-of-function lethality and redundancy. Furthermore, the ability of chemicals to be added at will and to act quickly can permit the study of processes that are highly dynamic such as endomembrane trafficking. An important aspect of utilizing small molecules effectively is to characterize bioactive chemicals in detail including an understanding of structure-activity relationships and the identification of active and inactive analogs. Bioactive chemicals can be useful as reagents to probe biological pathways directly. However, the identification of cognate targets and their pathways is also informative and can be achieved by screens for genetic resistance or hypersensitivity in Arabidopsis thaliana or other organisms from which the results can be translated to plants. In addition, there are approaches utilizing "tagged" chemical libraries that possess reactive moieties permitting the immobilization of active compounds. This opens the possibility for biochemical purification of putative cognate targets. We will review approaches to screen for bioactive chemicals that affect biological processes in Arabidopsis and provide several examples of the power and challenges inherent in this new approach in plant biology. PMID- 22303246 TI - The Arabidopsis cell division cycle. AB - Plant cells have evolved a complex circuitry to regulate cell division. In many aspects, the plant cell cycle follows a basic strategy similar to other eukaryotes. However, several key issues are unique to plant cells. In this chapter, both the conserved and unique cellular and molecular properties of the plant cell cycle are reviewed. In addition to division of individual cells, the specific characteristic of plant organogenesis and development make that cell proliferation control is of primary importance during development. Therefore, special attention should be given to consider plant cell division control in a developmental context. Proper organogenesis depends on the formation of different cell types. In plants, many of the processes leading to cell differentiation rely on the occurrence of a different cycle, termed the endoreplication cycle, whereby cells undergo repeated full genome duplication events in the absence of mitosis and increase their ploidy. Recent findings are focusing on the relevance of changes in chromatin organization for a correct cell cycle progression and, conversely, in the relevance of a correct functioning of chromatin remodelling complexes to prevent alterations in both the cell cycle and the endocycle. PMID- 22303247 TI - Aspartate-Derived Amino Acid Biosynthesis in Arabidopsis thaliana. AB - The aspartate-derived amino acid pathway in plants leads to the biosynthesis of lysine, methionine, threonine, and isoleucine. These four amino acids are essential in the diets of humans and other animals, but are present in growth limiting quantities in some of the world's major food crops. Genetic and biochemical approaches have been used for the functional analysis of almost all Arabidopsis thaliana enzymes involved in aspartate-derived amino acid biosynthesis. The branch-point enzymes aspartate kinase, dihydrodipicolinate synthase, homoserine dehydrogenase, cystathionine gamma synthase, threonine synthase, and threonine deaminase contain well-studied sites for allosteric regulation by pathway products and other plant metabolites. In contrast, relatively little is known about the transcriptional regulation of amino acid biosynthesis and the mechanisms that are used to balance aspartate-derived amino acid biosynthesis with other plant metabolic needs. The aspartate-derived amino acid pathway provides excellent examples of basic research conducted with A. thaliana that has been used to improve the nutritional quality of crop plants, in particular to increase the accumulation of lysine in maize and methionine in potatoes. PMID- 22303248 TI - Trehalose Metabolites in Arabidopsis-elusive, active and central. AB - Trehalose is an alpha, alpha-1, 1-linked glucose disaccharide. In plants, trehalose is synthesized in two steps. Firstly, trehalose-6-phosphate synthase (TPS) converts UDP-glucose and glucose-6-phosphate to trehalose-6-phosphate (T6P); secondly, T6P-phosphatase (TPP) converts T6P into trehalose and Pi. Trehalose is further cleaved into glucose by trehalase. In extracts of most plants, including Arabidopsis, levels of both trehalose and T6P are low, nearing detection limits, and this has delayed research into their function. Trehalose is transported widely in plants, but transport of T6P is not thought to occur except possibly at the subcellular level. Feeding trehalose to Arabidopsis seedlings alters carbon allocation with massive starch accumulation in cotyledons and leaves and absence of starch and growth in shoot and root apices.The Arabidopsis genome has experienced extensive radiation of genes likely encoding enzymes of T6P metabolism: 4 and 10 genes are found with homology to TPS and TPP respectively and 7 genes are found with homology to both TPS and TPP. Complementation of Saccharomyces cerevisiae mutants has shown that AtTPS1, AtTPPA and AtTPPB are functional enzymes. In contrast just a single gene encoding a protein with trehalase activity has been found. Whilst most TPS proteins appear cytosolic, strikingly, some TPPs appear targeted to chloroplasts; trehalase on the other hand is extracellular. Transporters of trehalose and T6P have yet to be described. Arabidopsis tps1 mutants are embryo lethal and results suggest that T6P is essential for several other steps in development including root growth and floral transition. Accordingly, altering T6P content has a profound effect on plant habitus and impacts metabolite profiles, sugar utilization and photosynthesis. These large effects have hindered dissection of cause and effect. In contrast, plants with large alterations in sucrose-6-phosphate concentrations are indistinguishable from wild type, suggesting very different functions for these compounds. Recently, T6P at low micromolar concentrations has been shown in vitro and in vivo to inhibit SnRK1 of the SNF1/AMPK group of protein kinases. This supports a function for T6P as a sugar signaling molecule integrating metabolism and development in plants in relation to carbon supply.Genetic engineering of Arabidopsis as well as tobacco, potato and rice with TPS or TPS/TPP protein fusions reveals that trehalose metabolism also mediates multiple abiotic stress tolerances. Trehalose applications also mediate biotic stress resistances. Both Escherichia coli and Saccharomyces cerevisiae TPS/TPP protein fusions can be used to engineer stress tolerance suggesting that metabolites rather than proteins of the trehalose pathway are key stress tolerance elicitors. Results underscore the central role of trehalose metabolites in integrating carbon metabolism and stress responses with plant development. PMID- 22303250 TI - Embryogenesis: pattern formation from a single cell. AB - During embryogenesis a single cell gives rise to a functional multicellular organism. In higher plants, as in many other multicellular systems, essential architectural features, such as body axes and major tissue layers are established early in embryogenesis and serve as a positional framework for subsequent pattern elaboration. In Arabidopsis, the apicalbasal axis and the radial pattern of tissues wrapped around it are already recognizable in young embryos of only about a hundred cells in size. This early axial pattern seems to provide a coordinate system for the embryonic initiation of shoot and root. Findings from genetic studies in Arabidopsis are revealing molecular mechanisms underlying the initial establishment of the axial core pattern and its subsequent elaboration into functional shoots and roots. The genetic programs operating in the early embryo organize functional cell patterns rapidly and reproducibly from minimal cell numbers. Understanding their molecular details could therefore greatly expand our ability to generate plant body patterns de novo, with important implications for plant breeding and biotechnology. PMID- 22303249 TI - Peroxisome biogenesis and function. AB - Peroxisomes are small and single membrane-delimited organelles that execute numerous metabolic reactions and have pivotal roles in plant growth and development. In recent years, forward and reverse genetic studies along with biochemical and cell biological analyses in Arabidopsis have enabled researchers to identify many peroxisome proteins and elucidate their functions. This review focuses on the advances in our understanding of peroxisome biogenesis and metabolism, and further explores the contribution of large-scale analysis, such as in sillco predictions and proteomics, in augmenting our knowledge of peroxisome function In Arabidopsis. PMID- 22303251 TI - From perception to activation: the molecular-genetic and biochemical landscape of disease resistance signaling in plants. AB - More than 60 years ago, H.H. Flor proposed the "Gene-for-Gene" hypothesis, which described the genetic relationship between host plants and pathogens. In the decades that followed Flor's seminal work, our understanding of the plant pathogen interaction has evolved into a sophisticated model, detailing the molecular genetic and biochemical processes that control host-range, disease resistance signaling and susceptibility. The interaction between plants and microbes is an intimate exchange of signals that has evolved for millennia, resulting in the modification and adaptation of pathogen virulence strategies and host recognition elements. In total, plants have evolved mechanisms to combat the ever-changing landscape of biotic interactions bombarding their environment, while in parallel, plant pathogens have co-evolved mechanisms to sense and adapt to these changes. On average, the typical plant is susceptible to attack by dozens of microbial pathogens, yet in most cases, remains resistant to many of these challenges. The sum of research in our field has revealed that these interactions are regulated by multiple layers of intimately linked signaling networks. As an evolved model of Flor's initial observations, the current paradigm in host-pathogen interactions is that pathogen effector molecules, in large part, drive the recognition, activation and subsequent physiological responses in plants that give rise to resistance and susceptibility. In this Chapter, we will discuss our current understanding of the association between plants and microbial pathogens, detailing the pressures placed on both host and microbe to either maintain disease resistance, or induce susceptibility and disease. From recognition to transcriptional reprogramming, we will review current data and literature that has advanced the classical model of the Gene-for Gene hypothesis to our current understanding of basal and effector triggered immunity. PMID- 22303252 TI - Phototropism: mechanism and outcomes. AB - Plants have evolved a wide variety of responses that allow them to adapt to the variable environmental conditions in which they find themselves growing. One such response is the phototropic response - the bending of a plant organ toward (stems and leaves) or away from (roots) a directional blue light source. Phototropism is one of several photoresponses of plants that afford mechanisms to alter their growth and development to changes in light intensity, quality and direction. Over recent decades much has been learned about the genetic, molecular and cell biological components involved in sensing and responding to phototropic stimuli. Many of these advances have been made through the utilization of Arabidopsis as a model for phototropic studies. Here we discuss such advances, as well as studies in other plant species where appropriate to the discussion of work in Arabidopsis. PMID- 22303254 TI - Regulation by polycomb and trithorax group proteins in Arabidopsis. AB - Polycomb group (PcG) and trithorax group (trxG) proteins are key regulators of homeotic genes and have crucial roles in cell proliferation, growth and development. PcG and trxG proteins form higher order protein complexes that contain SET domain proteins, with a histone methyltransferase (HMTase) activity, responsible for the different types of lysine methylation at the N-terminal tails of the core histone proteins. In recent years, genetic studies along with biochemical and cell biological analyses in Arabidopsis have enabled researchers to begin to understand how PcG and trxG proteins are recruited to chromatin and how they regulate their target genes and to elucidate their functions. This review focuses on the advances in our understanding of the biological roles of PcG and trxG proteins, their molecular mechanisms of action and further examines the role of histone marks in PcG and trxG regulation in Arabidopsis. PMID- 22303255 TI - Jasmonates. AB - ARABIDOPSIS IS A SUPERB MODEL FOR THE STUDY OF AN IMPORTANT SUBGROUP OF OXYLIPINS: the jasmonates. Jasmonates control many responses to cell damage and invasion and are essential for reproduction. Jasmonic acid (JA) is a prohormone and is conjugated to hydrophobic amino acids to produce regulatory ligands. The major receptor for active jasmonate ligands is closely related to auxin receptors and, as in auxin signaling, jasmonate signaling requires the destruction of repressor proteins. This chapter uses a frequently asked question (FAQ) approach and concludes with a practical section. PMID- 22303253 TI - Flower development. AB - Flowers are the most complex structures of plants. Studies of Arabidopsis thaliana, which has typical eudicot flowers, have been fundamental in advancing the structural and molecular understanding of flower development. The main processes and stages of Arabidopsis flower development are summarized to provide a framework in which to interpret the detailed molecular genetic studies of genes assigned functions during flower development and is extended to recent genomics studies uncovering the key regulatory modules involved. Computational models have been used to study the concerted action and dynamics of the gene regulatory module that underlies patterning of the Arabidopsis inflorescence meristem and specification of the primordial cell types during early stages of flower development. This includes the gene combinations that specify sepal, petal, stamen and carpel identity, and genes that interact with them. As a dynamic gene regulatory network this module has been shown to converge to stable multigenic profiles that depend upon the overall network topology and are thus robust, which can explain the canalization of flower organ determination and the overall conservation of the basic flower plan among eudicots. Comparative and evolutionary approaches derived from Arabidopsis studies pave the way to studying the molecular basis of diverse floral morphologies. PMID- 22303256 TI - Photorespiration. AB - Photorespiration is initiated by the oxygenase activity of ribulose-1,5 bisphosphate-carboxylase/oxygenase (RUBISCO), the same enzyme that is also responsible for CO(2) fixation in almost all photosynthetic organisms. Phosphoglycolate formed by oxygen fixation is recycled to the Calvin cycle intermediate phosphoglycerate in the photorespiratory pathway. This reaction cascade consumes energy and reducing equivalents and part of the afore fixed carbon is again released as CO(2). Because of this, photorespiration was often viewed as a wasteful process. Here, we review the current knowledge on the components of the photorespiratory pathway that has been mainly achieved through genetic and biochemical studies in Arabidopsis. Based on this knowledge, the energy costs of photorespiration are calculated, but the numerous positive aspects that challenge the traditional view of photorespiration as a wasteful pathway are also discussed. An outline of possible alternative pathways beside the major pathway is provided. We summarize recent results about photorespiration in photosynthetic organisms expressing a carbon concentrating mechanism and the implications of these results for understanding Arabidopsis photorespiration. Finally, metabolic engineering approaches aiming to improve plant productivity by reducing photorespiratory losses are evaluated. PMID- 22303257 TI - Glutathione transferases. AB - The 55 Arabidopsis glutathione transferases (GSTs) are, with one microsomal exception, a monophyletic group of soluble enzymes that can be divided into phi, tau, theta, zeta, lambda, dehydroascorbate reductase (DHAR) and TCHQD classes. The populous phi and tau classes are often highly stress inducible and regularly crop up in proteomic and transcriptomic studies. Despite much study on their xenobiotic-detoxifying activities their natural roles are unclear, although roles in defence-related secondary metabolism are likely. The smaller DHAR and lambda classes are likely glutathione-dependent reductases, the zeta class functions in tyrosine catabolism and the theta class has a putative role in detoxifying oxidised lipids. This review describes the evidence for the functional roles of GSTs and the potential for these enzymes to perform diverse functions that in many cases are not "glutathione transferase" activities. As well as biochemical data, expression data from proteomic and transcriptomic studies are included, along with subcellular localisation experiments and the results of functional genomic studies. PMID- 22303258 TI - The Biosynthetic Pathways for Shikimate and Aromatic Amino Acids in Arabidopsis thaliana. AB - The aromatic amino acids phenylalanine, tyrosine and tryptophan in plants are not only essential components of protein synthesis, but also serve as precursors for a wide range of secondary metabolites that are important for plant growth as well as for human nutrition and health. The aromatic amino acids are synthesized via the shikimate pathway followed by the branched aromatic amino acid metabolic pathway, with chorismate serving as a major branch point intermediate metabolite. Yet, the regulation of their synthesis is still far from being understood. So far, only three enzymes in this pathway, namely, chorismate mutase of phenylalanine and tyrosine synthesis, tryptophan synthase of tryptophan biosynthesis and arogenate dehydratase of phenylalanine biosynthesis, proved experimentally to be allosterically regulated. The major biosynthesis route of phenylalanine in plants occurs via arogenate. Yet, recent studies suggest that an alternative route of phynylalanine biosynthesis via phenylpyruvate may also exist in plants, similarly to many microorganisms. Several transcription factors regulating the expression of genes encoding enzymes of both the shikimate pathway and aromatic amino acid metabolism have also been recently identified in Arabidopsis and other plant species. PMID- 22303260 TI - Glucosinolate breakdown in Arabidopsis: mechanism, regulation and biological significance. AB - Glucosinolates are a group of thioglucosides in plants of the Brassicales order. Together with their hydrolytic enzymes, the myrosinases, they constitute the 'mustard oil bomb' involved in plant defense. Here we summarize recent studies in Arabidopsis that have provided molecular evidence that the glucosinolate myrosinase system is much more than a 'two-component defense system,' and started to unravel the roles of different glucosinolate breakdown pathways in the context of plant responses to biotic and abiotic stresses. PMID- 22303259 TI - Acyl-lipid metabolism. AB - Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. This function alone involves more than 10 membrane lipid classes, including the phospholipids, galactolipids, and sphingolipids, and within each class the variations in acyl chain composition expand the number of structures to several hundred possible molecular species. Acyl lipids in the form of triacylglycerol account for 35% of the weight of Arabidopsis seeds and represent their major form of carbon and energy storage. A layer of cutin and cuticular waxes that restricts the loss of water and provides protection from invasions by pathogens and other stresses covers the entire aerial surface of Arabidopsis. Similar functions are provided by suberin and its associated waxes that are localized in roots, seed coats, and abscission zones and are produced in response to wounding. This chapter focuses on the metabolic pathways that are associated with the biosynthesis and degradation of the acyl lipids mentioned above. These pathways, enzymes, and genes are also presented in detail in an associated website (ARALIP: http://aralip.plantbiology.msu.edu/). Protocols and methods used for analysis of Arabidopsis lipids are provided. Finally, a detailed summary of the composition of Arabidopsis lipids is provided in three figures and 15 tables. PMID- 22303262 TI - Branched-Chain Amino Acid Metabolism in Arabidopsis thaliana. AB - Valine, leucine and isoleucine form the small group of branched-chain amino acids (BCAAs) classified by their small branched hydrocarbon residues. Unlike animals, plants are able to de novo synthesize these amino acids from pyruvate, 2 oxobutanoate and acetyl-CoA. In plants, biosynthesis follows the typical reaction pathways established for the formation of these amino acids in microorganisms. Val and Ile are synthesized in two parallel pathways using a single set of enzymes. The pathway to Leu branches of from the final intermediate of Val biosynthesis. The formation of this amino acid requires a three-step pathway generating a 2-oxoacid elongated by a methylene group. In Arabidopsis thaliana and other Brassicaceae, a homologous three-step pathway is also involved in Met chain elongation required for the biosynthesis of aliphatic glucosinolates, an important class of specialized metabolites in Brassicaceae. This is a prime example for the evolutionary relationship of pathways from primary and specialized metabolism. Similar to animals, plants also have the ability to degrade BCAAs. The importance of BCAA turnover has long been unclear, but now it seems apparent that the breakdown process might by relevant under certain environmental conditions. In this review, I summarize the current knowledge about BCAA metabolism, its regulation and its particular features in Arabidopsis thaliana. PMID- 22303261 TI - Necrotroph attacks on plants: wanton destruction or covert extortion? AB - Necrotrophic pathogens cause major pre- and post-harvest diseases in numerous agronomic and horticultural crops inflicting significant economic losses. In contrast to biotrophs, obligate plant parasites that infect and feed on living cells, necrotrophs promote the destruction of host cells to feed on their contents. This difference underpins the divergent pathogenesis strategies and plant immune responses to biotrophic and necrotrophic infections. This chapter focuses on Arabidopsis immunity to necrotrophic pathogens. The strategies of infection, virulence and suppression of host defenses recruited by necrotrophs and the variation in host resistance mechanisms are highlighted. The multiplicity of intraspecific virulence factors and species diversity in necrotrophic organisms corresponds to variations in host resistance strategies. Resistance to host-specific necrotophs is monogenic whereas defense against broad host necrotrophs is complex, requiring the involvement of many genes and pathways for full resistance. Mechanisms and components of immunity such as the role of plant hormones, secondary metabolites, and pathogenesis proteins are presented. We will discuss the current state of knowledge of Arabidopsis immune responses to necrotrophic pathogens, the interactions of these responses with other defense pathways, and contemplate on the directions of future research. PMID- 22303263 TI - Progress and Promise in using Arabidopsis to Study Adaptation, Divergence, and Speciation. AB - Fundamental questions remain to be answered on how lineages split and new species form. The Arabidopsis genus, with several increasingly well characterized species closely related to the model system A. thaliana, provides a rare opportunity to address key questions in speciation research. Arabidopsis species, and in some cases populations within a species, vary considerably in their habitat preferences, adaptations to local environments, mating system, life history strategy, genome structure and chromosome number. These differences provide numerous open doors for understanding the role these factors play in population divergence and how they may cause barriers to arise among nascent species. Molecular tools available in A. thaliana are widely applicable to its relatives, and together with modern comparative genomic approaches they will provide new and increasingly mechanistic insights into the processes underpinning lineage divergence and speciation. We will discuss recent progress in understanding the molecular basis of local adaptation, reproductive isolation and genetic incompatibility, focusing on work utilizing the Arabidopsis genus, and will highlight several areas in which additional research will provide meaningful insights into adaptation and speciation processes in this genus. PMID- 22303265 TI - Proline metabolism and its implications for plant-environment interaction. AB - Proline has long been known to accumulate in plants experiencing water limitation and this has driven studies of proline as a beneficial solute allowing plants to increase cellular osmolarity during water limitation. Proline metabolism also has roles in redox buffering and energy transfer and is involved in plant pathogen interaction and programmed cell death. Some of these unique roles of proline depend on the properties of proline itself, whereas others depend on the "proline cycle" of coordinated proline synthesis in the chloroplast and cytoplasm with proline catabolism in the mitochondria. The regulatory mechanisms controlling proline metabolism, intercellular and intracellular transport and connections of proline to other metabolic pathways are all important to the in vivo functions of proline metabolism. Connections of proline metabolism to the oxidative pentose phosphate pathway and glutamate-glutamine metabolism are of particular interest. The N-acetyl glutamate pathway can also produce ornithine and, potentially, proline but its role and activity are unclear. Use of model systems such as Arabidopsis thaliana to better understand both these long studied and newly emerging functions of proline can help in the design of next-generation experiments testing whether proline metabolism is a promising metabolic engineering target for improving stress resistance of economically important plants. PMID- 22303266 TI - Histidine biosynthesis. AB - Histidine (His) is one of the standard amino acids in proteins, and plays a critical role in plant growth and development. The chemical properties of the imidazole side group allow His to participate in acid-base catalysis, and in the co-ordination of metal ions. Despite the biological importance of this molecule, His biosynthesis has been somewhat neglected in plants, in stark contrast to micro-organisms where the study of this pathway was fundamental in the discovery of operon structure and regulation by attenuation. With the recent isolation of histidinol-phosphate phosphatase, all the enzymes of His biosynthesis have now been identified in Arabidopsis, and several lines of evidence have implicated ATP phosphoribosyl transferase (which catalyses the first committed step of the pathway) as playing an important role in the regulation of this pathway. However, little is known about the transcriptional regulation of the His biosynthetic genes, nor how demand for this amino acid is balanced with other metabolic requirements in plants. Similarly, the pathway of His catabolism has yet to be determined. PMID- 22303264 TI - The Arabidopsis nuclear pore and nuclear envelope. AB - The nuclear envelope is a double membrane structure that separates the eukaryotic cytoplasm from the nucleoplasm. The nuclear pores embedded in the nuclear envelope are the sole gateways for macromolecular trafficking in and out of the nucleus. The nuclear pore complexes assembled at the nuclear pores are large protein conglomerates composed of multiple units of about 30 different nucleoporins. Proteins and RNAs traffic through the nuclear pore complexes, enabled by the interacting activities of nuclear transport receptors, nucleoporins, and elements of the Ran GTPase cycle. In addition to directional and possibly selective protein and RNA nuclear import and export, the nuclear pore gains increasing prominence as a spatial organizer of cellular processes, such as sumoylation and desumoylation. Individual nucleoporins and whole nuclear pore subcomplexes traffic to specific mitotic locations and have mitotic functions, for example at the kinetochores, in spindle assembly, and in conjunction with the checkpoints. Mutants of nucleoporin genes and genes of nuclear transport components lead to a wide array of defects from human diseases to compromised plant defense responses. The nuclear envelope acts as a repository of calcium, and its inner membrane is populated by functionally unique proteins connected to both chromatin and-through the nuclear envelope lumen-the cytoplasmic cytoskeleton. Plant nuclear pore and nuclear envelope research predominantly focusing on Arabidopsis as a model-is discovering both similarities and surprisingly unique aspects compared to the more mature model systems. This chapter gives an overview of our current knowledge in the field and of exciting areas awaiting further exploration. PMID- 22303267 TI - Glutathione. AB - Glutathione is a simple sulfur compound composed of three amino acids and the major non-protein thiol in many organisms, including plants. The functions of glutathione are manifold but notably include redox-homeostatic buffering. Glutathione status is modulated by oxidants as well as by nutritional and other factors, and can influence protein structure and activity through changes in thiol-disulfide balance. For these reasons, glutathione is a transducer that integrates environmental information into the cellular network. While the mechanistic details of this function remain to be fully elucidated, accumulating evidence points to important roles for glutathione and glutathione-dependent proteins in phytohormone signaling and in defense against biotic stress. Work in Arabidopsis is beginning to identify the processes that govern glutathione status and that link it to signaling pathways. As well as providing an overview of the components that regulate glutathione homeostasis (synthesis, degradation, transport, and redox turnover), the present discussion considers the roles of this metabolite in physiological processes such as light signaling, cell death, and defense against microbial pathogen and herbivores. PMID- 22303268 TI - Terpene Specialized Metabolism in Arabidopsis thaliana. AB - Terpenes constitute the largest class of plant secondary (or specialized) metabolites, which are compounds of ecological function in plant defense or the attraction of beneficial organisms. Using biochemical and genetic approaches, nearly all Arabidopsis thaliana (Arabidopsis) enzymes of the core biosynthetic pathways producing the 5-carbon building blocks of terpenes have been characterized and closer insight has been gained into the transcriptional and posttranscriptional/translational mechanisms regulating these pathways. The biochemical function of most prenyltransferases, the downstream enzymes that condense the C(5)-precursors into central 10-, 15-, and 20-carbon prenyldiphosphate intermediates, has been described, although the function of several isoforms of C(20)-prenyltranferases is not well understood. Prenyl diphosphates are converted to a variety of C(10)-, C(15)-, and C(20)-terpene products by enzymes of the terpene synthase (TPS) family. Genomic organization of the 32 Arabidopsis TPS genes indicates a species-specific divergence of terpene synthases with tissue- and cell-type specific expression profiles that may have emerged under selection pressures by different organisms. Pseudogenization, differential expression, and subcellular segregation of TPS genes and enzymes contribute to the natural variation of terpene biosynthesis among Arabidopsis accessions (ecotypes) and species. Arabidopsis will remain an important model to investigate the metabolic organization and molecular regulatory networks of terpene specialized metabolism in relation to the biological activities of terpenes. PMID- 22303269 TI - Cytochromes p450. AB - There are 244 cytochrome P450 genes (and 28 pseudogenes) in the Arabidopsis genome. P450s thus form one of the largest gene families in plants. Contrary to what was initially thought, this family diversification results in very limited functional redundancy and seems to mirror the complexity of plant metabolism. P450s sometimes share less than 20% identity and catalyze extremely diverse reactions leading to the precursors of structural macromolecules such as lignin, cutin, suberin and sporopollenin, or are involved in biosynthesis or catabolism of all hormone and signaling molecules, of pigments, odorants, flavors, antioxidants, allelochemicals and defense compounds, and in the metabolism of xenobiotics. The mechanisms of gene duplication and diversification are getting better understood and together with co-expression data provide leads to functional characterization. PMID- 22303270 TI - Tetrapyrrole Metabolism in Arabidopsis thaliana. AB - Higher plants produce four classes of tetrapyrroles, namely, chlorophyll (Chl), heme, siroheme, and phytochromobilin. In plants, tetrapyrroles play essential roles in a wide range of biological activities including photosynthesis, respiration and the assimilation of nitrogen/sulfur. All four classes of tetrapyrroles are derived from a common biosynthetic pathway that resides in the plastid. In this article, we present an overview of tetrapyrrole metabolism in Arabidopsis and other higher plants, and we describe all identified enzymatic steps involved in this metabolism. We also summarize recent findings on Chl biosynthesis and Chl breakdown. Recent advances in this field, in particular those on the genetic and biochemical analyses of novel enzymes, prompted us to redraw the tetrapyrrole metabolic pathways. In addition, we also summarize our current understanding on the regulatory mechanisms governing tetrapyrrole metabolism. The interactions of tetrapyrrole biosynthesis and other cellular processes including the plastid-to-nucleus signal transduction are discussed. PMID- 22303271 TI - The Functions of RNA-Dependent RNA Polymerases in Arabidopsis. AB - One recently identified mechanism that regulates mRNA abundance is RNA silencing, and pioneering work in Arabidopsis thaliana and other genetic model organisms helped define this process. RNA silencing pathways are triggered by either self complementary fold-back structures or the production of double-stranded RNA (dsRNA) that gives rise to small RNAs (smRNAs) known as microRNAs (miRNAs) or small-interfering RNAs (siRNAs). These smRNAs direct sequence-specific regulation of various gene transcripts, repetitive sequences, viruses, and mobile elements via RNA cleavage, translational inhibition, or transcriptional silencing through DNA methylation and heterochromatin formation. Early genetic screens in Arabidopsis were instrumental in uncovering numerous proteins required for these important regulatory pathways. Among the factors identified by these studies were RNA-dependent RNA polymerases (RDRs), which are proteins that synthesize siRNA producing dsRNA molecules using a single-stranded RNA (ssRNA) molecule as a template. Recently, a growing body of evidence has implicated RDR-dependent RNA silencing in many different aspects of plant biology ranging from reproductive development to pathogen resistance. Here, we focus on the specific functions of the six Arabidopsis RDRs in RNA silencing, their ssRNA substrates and resulting RDR-dependent smRNAs, and the numerous biological functions of these proteins in plant development and stress responses. PMID- 22303273 TI - The Function of the CLE Peptides in Plant Development and Plant-Microbe Interactions. AB - The CLAVATA3 (CLV3)/ENDOSPERM SURROUNDING REGION (ESR) (CLE) peptides consist of 12 or 13 amino acids, including hydroxylated proline residues that may or may not contain sugar modifications, and function in a non-cell-autonomous fashion. The CLE gene was first reported in Zea mays (maize) as an endosperm-specific gene, ESR, in 1997 (Opsahl-Ferstad et al., 1997). CLE genes encode secreted peptides that function in the extracellular space as intercellular signaling molecules and bind to cellular surface receptor-like proteins to transmit a signal. CLE peptides regulate various physiological and developmental processes and its signaling pathway are conserved in diverse land plants. Recent CLE functional studies have pointed to their significance in regulating meristematic activity in plant meristems, through the CLE-receptor kinase-WOX signaling node. CLV3 and CLE40 are responsible for maintenance of shoot apical meristem (SAM) and root apical meristem (RAM) function, regulating homeodomain transcription factors, WUSCHEL (WUS) and WUSCHEL-related homeobox 5 (WOX5), respectively. CLE and WOX form an interconnected and self-correcting feedback loop to provide robustness to stem cell homeostasis. CLE peptides are required for certain plant-microbe interactions, such as those that occur during legume symbiosis and phytopathogenic nematode infection. Understanding the molecular properties of CLE peptides may provide insight into plant cell-cell communication, and therefore also into plant-microbe interactions. PMID- 22303272 TI - Phytochrome signaling mechanisms. AB - Phytochromes are red (R)/far-red (FR) light photoreceptors that play fundamental roles in photoperception of the light environment and the subsequent adaptation of plant growth and development. There are five distinct phytochromes in Arabidopsis thaliana, designated phytochrome A (phyA) to phyE. phyA is light labile and is the primary photoreceptor responsible for mediating photomorphogenic responses in FR light, whereas phyB-phyE are light stable, and phyB is the predominant phytochrome regulating de-etiolation responses in R light. Phytochromes are synthesized in the cytosol in their inactive Pr form. Upon light irradiation, phytochromes are converted to the biologically active Pfr form, and translocate into the nucleus. phyB can enter the nucleus by itself in response to R light, whereas phyA nuclear import depends on two small plant specific proteins FAR-RED ELONGATED HYPOCOTYL 1 (FHY1) and FHY1-LIKE (FHL). Phytochromes may function as light-regulated serine/threonine kinases, and can phosphorylate several substrates, including themselves in vitro. Phytochromes are phosphoproteins, and can be dephosphorylated by a few protein phosphatases. Photoactivated phytochromes rapidly change the expression of light-responsive genes by repressing the activity of CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), an E3 ubiquitin ligase targeting several photomorphogenesis-promoting transcription factors for degradation, and by inducing rapid phosphorylation and degradation of Phytochrome-Interacting Factors (PIFs), a group of bHLH transcription factors repressing photomorphogenesis. Phytochromes are targeted by COP1 for degradation via the ubiquitin/26S proteasome pathway. PMID- 22303274 TI - Small post-translationally modified Peptide signals in Arabidopsis. AB - Recent biochemical, genetic and bioinformatic studies have demonstrated that peptide signaling plays a greater than anticipated role in various aspects of plant growth and development. More than a dozen secreted peptides are now recognized as important signals that mediate cell-to-cell communication. Secreted peptide signals often undergo post-translational modification and proteolytic processing, which are important for their function. Such "small post translationally modified peptide signals" constitute one of the largest groups of peptide signals in plants. In parallel with the discovery of peptide signals, specific receptors for such peptides were identified as being membrane-localized receptor kinases, the largest family of receptor-like molecules in plants. These findings illustrate the critical roles of small peptide ligand-receptor pairs in plant growth and development. This review outlines recent research into secreted peptide signals in plants by focusing on small post-translationally modified peptides. PMID- 22303276 TI - The phenylpropanoid pathway in Arabidopsis. AB - The phenylpropanoid pathway serves as a rich source of metabolites in plants, being required for the biosynthesis of lignin, and serving as a starting point for the production of many other important compounds, such as the flavonoids, coumarins, and lignans. In spite of the fact that the phenylpropanoids and their derivatives are sometimes classified as secondary metabolites, their relevance to plant survival has been made clear via the study of Arabidopsis and other plant species. As a model system, Arabidopsis has helped to elucidate many details of the phenylpropanoid pathway, its enzymes and intermediates, and the interconnectedness of the pathway with plant metabolism as a whole. These advances in our understanding have been made possible in large part by the relative ease with which mutations can be generated, identified, and studied in Arabidopsis. Herein, we provide an overview of the research progress that has been made in recent years, emphasizing both the genes (and gene families) associated with the phenylpropanoid pathway in Arabidopsis, and the end products that have contributed to the identification of many mutants deficient in the phenylpropanoid metabolism: the sinapate esters. PMID- 22303275 TI - Brassinosteroids. AB - Brassinosteroids (BRs) are endogenous plant hormones essential for the proper regulation of multiple physiological processes required for normal plant growth and development. Since their discovery more than 30 years ago, extensive research on the mechanisms of BR action using biochemistry, mutant studies, proteomics and genome-wide transcriptome analyses, has helped refine the BR biosynthetic pathway, identify the basic molecular components required to relay the BR signal from perception to gene regulation, and expand the known physiological responses influenced by BRs. These mechanistic advances have helped answer the intriguing question of how BRs can have such dramatic pleiotropic effects on a broad range of diverse developmental pathways and have further pointed to BR interactions with other plant hormones and environmental cues. This chapter briefly reviews historical aspects of BR research and then summarizes the current state of knowledge on BR biosynthesis, metabolism and signal transduction. Recent studies uncovering novel phosphorelays and gene regulatory networks through which BR influences both vegetative and reproductive development are examined and placed in the context of known BR physiological responses including cell elongation and division, vascular differentiation, flowering, pollen development and photomorphogenesis. PMID- 22303277 TI - Plant ABC Transporters. AB - ABC transporters constitute one of the largest protein families found in all living organisms. ABC transporters are driven by ATP hydrolysis and can act as exporters as well as importers. The plant genome encodes for more than 100 ABC transporters, largely exceeding that of other organisms. In Arabidopsis, only 22 out of 130 have been functionally analyzed. They are localized in most membranes of a plant cell such as the plasma membrane, the tonoplast, chloroplasts, mitochondria and peroxisomes and fulfill a multitude of functions. Originally identified as transporters involved in detoxification processes, they have later been shown to be required for organ growth, plant nutrition, plant development, response to abiotic stresses, pathogen resistance and the interaction of the plant with its environment. To fulfill these roles they exhibit different substrate specifies by e.g. depositing surface lipids, accumulating phytate in seeds, and transporting the phytohormones auxin and abscisic acid. The aim of this review is to give an insight into the functions of plant ABC transporters and to show their importance for plant development and survival. PMID- 22303278 TI - Molecular Biology, Biochemistry and Cellular Physiology of Cysteine Metabolism in Arabidopsis thaliana. AB - Cysteine is one of the most versatile molecules in biology, taking over such different functions as catalysis, structure, regulation and electron transport during evolution. Research on Arabidopsis has contributed decisively to the understanding of cysteine synthesis and its role in the assimilatory pathways of S, N and C in plants. The multimeric cysteine synthase complex is present in the cytosol, plastids and mitochondria and forms the centre of a unique metabolic sensing and signaling system. Its association is reversible, rendering the first enzyme of cysteine synthesis active and the second one inactive, and vice-versa. Complex formation is triggered by the reaction intermediates of cysteine synthesis in response to supply and demand and gives rise to regulation of genes of sulfur metabolism to adjust cellular sulfur homeostasis. Combinations of biochemistry, forward and reverse genetics, structural- and cell-biology approaches using Arabidopsis have revealed new enzyme functions and the unique pattern of spatial distribution of cysteine metabolism in plant cells. These findings place the synthesis of cysteine in the centre of the network of primary metabolism. PMID- 22303279 TI - The female gametophyte. AB - The angiosperm female gametophyte is critical for plant reproduction. It contains the egg cell and central cell that become fertilized and give rise to the embryo and endosperm of the seed, respectively. Female gametophyte development begins early in ovule development with the formation of a diploid megaspore mother cell that undergoes meiosis. One resulting haploid megaspore then develops into the female gametophyte. Genetic and epigenetic processes mediate specification of megaspore mother cell identity and limit megaspore mother cell formation to a single cell per ovule. Auxin gradients influence female gametophyte polarity and a battery of transcription factors mediate female gametophyte cell specification and differentiation. The mature female gametophyte secretes peptides that guide the pollen tube to the embryo sac and contains protein complexes that prevent seed development before fertilization. Post-fertilization, the female gametophyte influences seed development through maternal-effect genes and by regulating parental contributions. Female gametophytes can form by an asexual process called gametophytic apomixis, which involves formation of a diploid female gametophyte and fertilization-independent development of the egg into the embryo. These functions collectively underscore the important role of the female gametophyte in seed and food production. PMID- 22303280 TI - Salicylic Acid biosynthesis and metabolism. AB - Salicylic acid (SA) has been shown to regulate various aspects of growth and development; it also serves as a critical signal for activating disease resistance in Arabidopsis thaliana and other plant species. This review surveys the mechanisms involved in the biosynthesis and metabolism of this critical plant hormone. While a complete biosynthetic route has yet to be established, stressed Arabidopsis appear to synthesize SA primarily via an isochorismate-utilizing pathway in the chloroplast. A distinct pathway utilizing phenylalanine as the substrate also may contribute to SA accumulation, although to a much lesser extent. Once synthesized, free SA levels can be regulated by a variety of chemical modifications. Many of these modifications inactivate SA; however, some confer novel properties that may aid in long distance SA transport or the activation of stress responses complementary to those induced by free SA. In addition, a number of factors that directly or indirectly regulate the expression of SA biosynthetic genes or that influence the rate of SA catabolism have been identified. An integrated model, encompassing current knowledge of SA metabolism in Arabidopsis, as well as the influence other plant hormones exert on SA metabolism, is presented. PMID- 22303281 TI - Reconstructing speech from human auditory cortex. AB - How the human auditory system extracts perceptually relevant acoustic features of speech is unknown. To address this question, we used intracranial recordings from nonprimary auditory cortex in the human superior temporal gyrus to determine what acoustic information in speech sounds can be reconstructed from population neural activity. We found that slow and intermediate temporal fluctuations, such as those corresponding to syllable rate, were accurately reconstructed using a linear model based on the auditory spectrogram. However, reconstruction of fast temporal fluctuations, such as syllable onsets and offsets, required a nonlinear sound representation based on temporal modulation energy. Reconstruction accuracy was highest within the range of spectro-temporal fluctuations that have been found to be critical for speech intelligibility. The decoded speech representations allowed readout and identification of individual words directly from brain activity during single trial sound presentations. These findings reveal neural encoding mechanisms of speech acoustic parameters in higher order human auditory cortex. PMID- 22303282 TI - Pulsed feedback defers cellular differentiation. AB - Environmental signals induce diverse cellular differentiation programs. In certain systems, cells defer differentiation for extended time periods after the signal appears, proliferating through multiple rounds of cell division before committing to a new fate. How can cells set a deferral time much longer than the cell cycle? Here we study Bacillus subtilis cells that respond to sudden nutrient limitation with multiple rounds of growth and division before differentiating into spores. A well-characterized genetic circuit controls the concentration and phosphorylation of the master regulator Spo0A, which rises to a critical concentration to initiate sporulation. However, it remains unclear how this circuit enables cells to defer sporulation for multiple cell cycles. Using quantitative time-lapse fluorescence microscopy of Spo0A dynamics in individual cells, we observed pulses of Spo0A phosphorylation at a characteristic cell cycle phase. Pulse amplitudes grew systematically and cell-autonomously over multiple cell cycles leading up to sporulation. This pulse growth required a key positive feedback loop involving the sporulation kinases, without which the deferral of sporulation became ultrasensitive to kinase expression. Thus, deferral is controlled by a pulsed positive feedback loop in which kinase expression is activated by pulses of Spo0A phosphorylation. This pulsed positive feedback architecture provides a more robust mechanism for setting deferral times than constitutive kinase expression. Finally, using mathematical modeling, we show how pulsing and time delays together enable "polyphasic" positive feedback, in which different parts of a feedback loop are active at different times. Polyphasic feedback can enable more accurate tuning of long deferral times. Together, these results suggest that Bacillus subtilis uses a pulsed positive feedback loop to implement a "timer" that operates over timescales much longer than a cell cycle. PMID- 22303283 TI - Desperately seeking stable 50-year-old landscapes with patches and long, wide corridors. PMID- 22303284 TI - Built-in timer delays differentiation. PMID- 22303285 TI - Doubly illegal: Qualitative accounts of underage alcohol access through theft. AB - This study investigated sources of alcohol for underage drinkers. In-depth, semi structured interviews were individually conducted with 47 youths, ages 15-18, who reported drinking within the last 12 months, to explore alcohol access. Theft was one method that some youths reported using to obtain alcohol. In addition to 9% of respondents who reported stealing alcohol from commercial outlets themselves, a total of 26% respondents reported occasions when their close friends stole alcohol. Our findings unveiled that teens had a body of knowledge that some drew upon for stealing alcohol. Youths revealed detailed knowledge about store layout, theft protection devices and store policies. In particular, respondents disclosed knowledge about which aisles have blind spots, how to remove security tops on bottles, and no-chase policies. Theft of alcohol from commercial sources may be reduced by examining the weaknesses of existing theft prevention practices, and revising store policies. PMID- 22303286 TI - Effects of two commercial electronic prescribing systems on prescribing error rates in hospital in-patients: a before and after study. AB - BACKGROUND: Considerable investments are being made in commercial electronic prescribing systems (e-prescribing) in many countries. Few studies have measured or evaluated their effectiveness at reducing prescribing error rates, and interactions between system design and errors are not well understood, despite increasing concerns regarding new errors associated with system use. This study evaluated the effectiveness of two commercial e-prescribing systems in reducing prescribing error rates and their propensities for introducing new types of error. METHODS AND RESULTS: We conducted a before and after study involving medication chart audit of 3,291 admissions (1,923 at baseline and 1,368 post e prescribing system) at two Australian teaching hospitals. In Hospital A, the Cerner Millennium e-prescribing system was implemented on one ward, and three wards, which did not receive the e-prescribing system, acted as controls. In Hospital B, the iSoft MedChart system was implemented on two wards and we compared before and after error rates. Procedural (e.g., unclear and incomplete prescribing orders) and clinical (e.g., wrong dose, wrong drug) errors were identified. Prescribing error rates per admission and per 100 patient days; rates of serious errors (5-point severity scale, those >=3 were categorised as serious) by hospital and study period; and rates and categories of postintervention "system-related" errors (where system functionality or design contributed to the error) were calculated. Use of an e-prescribing system was associated with a statistically significant reduction in error rates in all three intervention wards (respectively reductions of 66.1% [95% CI 53.9%-78.3%]; 57.5% [33.8% 81.2%]; and 60.5% [48.5%-72.4%]). The use of the system resulted in a decline in errors at Hospital A from 6.25 per admission (95% CI 5.23-7.28) to 2.12 (95% CI 1.71-2.54; p<0.0001) and at Hospital B from 3.62 (95% CI 3.30-3.93) to 1.46 (95% CI 1.20-1.73; p<0.0001). This decrease was driven by a large reduction in unclear, illegal, and incomplete orders. The Hospital A control wards experienced no significant change (respectively -12.8% [95% CI -41.1% to 15.5%]; -11.3% [ 40.1% to 17.5%]; -20.1% [-52.2% to 12.4%]). There was limited change in clinical error rates, but serious errors decreased by 44% (0.25 per admission to 0.14; p = 0.0002) across the intervention wards compared to the control wards (17% reduction; 0.30-0.25; p = 0.40). Both hospitals experienced system-related errors (0.73 and 0.51 per admission), which accounted for 35% of postsystem errors in the intervention wards; each system was associated with different types of system related errors. CONCLUSIONS: Implementation of these commercial e-prescribing systems resulted in statistically significant reductions in prescribing error rates. Reductions in clinical errors were limited in the absence of substantial decision support, but a statistically significant decline in serious errors was observed. System-related errors require close attention as they are frequent, but are potentially remediable by system redesign and user training. Limitations included a lack of control wards at Hospital B and an inability to randomize wards to the intervention. PMID- 22303287 TI - Hitting hotspots: spatial targeting of malaria for control and elimination. PMID- 22303288 TI - The role of health systems factors in facilitating access to psychotropic medicines: a cross-sectional analysis of the WHO-AIMS in 63 low- and middle income countries. AB - BACKGROUND: Neuropsychiatric conditions comprise 14% of the global burden of disease and 30% of all noncommunicable disease. Despite the existence of cost effective interventions, including administration of psychotropic medicines, the number of persons who remain untreated is as high as 85% in low- and middle income countries (LAMICs). While access to psychotropic medicines varies substantially across countries, no studies to date have empirically investigated potential health systems factors underlying this issue. METHODS AND FINDINGS: This study uses a cross-sectional sample of 63 LAMICs and country regions to identify key health systems components associated with access to psychotropic medicines. Data from countries that completed the World Health Organization Assessment Instrument for Mental Health Systems (WHO-AIMS) were included in multiple regression analyses to investigate the role of five major mental health systems domains in shaping medicine availability and affordability. These domains are: mental health legislation, human rights implementations, mental health care financing, human resources, and the role of advocacy groups. Availability of psychotropic medicines was associated with features of all five mental health systems domains. Most notably, within the domain of mental health legislation, a comprehensive national mental health plan was associated with 15% greater availability; and in terms of advocacy groups, the participation of family-based organizations in the development of mental health legislation was associated with 17% greater availability. Only three measures were related with affordability of medicines to consumers: level of human resources, percentage of countries' health budget dedicated to mental health, and availability of mental health care in prisons. Controlling for country development, as measured by the Human Development Index, health systems features were associated with medicine availability but not affordability. CONCLUSIONS: Results suggest that strengthening particular facets of mental health systems might improve availability of psychotropic medicines and that overall country development is associated with affordability. PMID- 22303289 TI - A new year at PLoS Medicine: maintaining a focus on the world's health priorities and identifying the gaps. PMID- 22303290 TI - Structural Anisotropy in Polar Fluids Subjected to Periodic Boundary Conditions. AB - A heuristic model based on dielectric continuum theory for the long-range solvation free energy of a dipolar system possessing periodic boundary conditions (PBCs) is presented. The predictions of the model are compared to simulation results for Stockmayer fluids simulated using three different cell geometries. The boundary effects induced by the PBCs are shown to lead to anisotropies in the apparent dielectric constant and the long-range solvation free energy of as much as 50%. However, the sum of all of the anisotropic energy contributions yields a value that is very close to the isotropic one derived from dielectric continuum theory, leading to a total system energy close to the dielectric value. It is finally shown that the leading-order contribution to the energetic and structural anisotropy is significantly smaller in the noncubic simulation cell geometries compared to when using a cubic simulation cell. PMID- 22303291 TI - Identification of genetic determinants and enzymes involved with the amidation of glutamic acid residues in the peptidoglycan of Staphylococcus aureus. AB - The glutamic acid residues of the peptidoglycan of Staphylococcus aureus and many other bacteria become amidated by an as yet unknown mechanism. In this communication we describe the identification, in the genome of S. aureus strain COL, of two co-transcribed genes, murT and gatD, which are responsible for peptidoglycan amidation. MurT and GatD have sequence similarity to substrate binding domains in Mur ligases (MurT) and to the catalytic domain in CobB/CobQ like glutamine amidotransferases (GatD). The amidation of glutamate residues in the stem peptide of S. aureus peptidoglycan takes place in a later step than the cytoplasmic phase--presumably the lipid phase--of the biosynthesis of the S. aureus cell wall precursor. Inhibition of amidation caused reduced growth rate, reduced resistance to beta-lactam antibiotics and increased sensitivity to lysozyme which inhibited culture growth and caused degradation of the peptidoglycan. PMID- 22303292 TI - The missing chain. PMID- 22303293 TI - Toward a New Gold Standard for Early Safety: Automated Temperature-Controlled hERG Test on the PatchLiner. AB - The Patchliner(r) temperature-controlled automated patch clamp system was evaluated for testing drug effects on potassium currents through human ether-a-go go related gene (hERG) channels expressed in Chinese hamster ovary cells at 35-37 degrees C. IC(50) values for a set of reference drugs were compared with those obtained using the conventional voltage clamp technique. The results showed good correlation between the data obtained using automated and conventional electrophysiology. Based on these results, the Patchliner((r)) represents an innovative automated electrophysiology platform for conducting the hERG assay that substantially increases throughput and has the advantage of operating at physiological temperature. It allows fast, accurate, and direct assessment of channel function to identify potential proarrhythmic side effects and sets a new standard in ion channel research for drug safety testing. PMID- 22303294 TI - Cardiac Safety Implications of hNav1.5 Blockade and a Framework for Pre-Clinical Evaluation. AB - The human cardiac sodium channel (hNav1.5, encoded by the SCN5A gene) is critical for action potential generation and propagation in the heart. Drug-induced sodium channel inhibition decreases the rate of cardiomyocyte depolarization and consequently conduction velocity and can have serious implications for cardiac safety. Genetic mutations in hNav1.5 have also been linked to a number of cardiac diseases. Therefore, off-target hNav1.5 inhibition may be considered a risk marker for a drug candidate. Given the potential safety implications for patients and the costs of late stage drug development, detection, and mitigation of hNav1.5 liabilities early in drug discovery and development becomes important. In this review, we describe a pre-clinical strategy to identify hNav1.5 liabilities that incorporates in vitro, in vivo, and in silico techniques and the application of this information in the integrated risk assessment at different stages of drug discovery and development. PMID- 22303295 TI - Hemispheric asymmetries: the comparative view. AB - Hemispheric asymmetries play an important role in almost all cognitive functions. For more than a century, they were considered to be uniquely human but now an increasing number of findings in all vertebrate classes make it likely that we inherited our asymmetries from common ancestors. Thus, studying animal models could provide unique insights into the mechanisms of lateralization. We outline three such avenues of research by providing an overview of experiments on left right differences in the connectivity of sensory systems, the embryonic determinants of brain asymmetries, and the genetics of lateralization. All these lines of studies could provide a wealth of insights into our own asymmetries that should and will be exploited by future analyses. PMID- 22303296 TI - Origin and evolution of antibiotic resistance: the common mechanisms of emergence and spread in water bodies. AB - The environment, and especially freshwater, constitutes a reactor where the evolution and the rise of new resistances occur. In water bodies such as waste water effluents, lakes, and rivers or streams, bacteria from different sources, e.g., urban, industrial, and agricultural waste, probably selected by intensive antibiotic usage, are collected and mixed with environmental species. This may cause two effects on the development of antibiotic resistances: first, the contamination of water by antibiotics or other pollutants lead to the rise of resistances due to selection processes, for instance, of strains over-expressing broad range defensive mechanisms, such as efflux pumps. Second, since environmental species are provided with intrinsic antibiotic resistance mechanisms, the mixture with allochthonous species is likely to cause genetic exchange. In this context, the role of phages and integrons for the spread of resistance mechanisms appears significant. Allochthonous species could acquire new resistances from environmental donors and introduce the newly acquired resistance mechanisms into the clinics. This is illustrated by clinically relevant resistance mechanisms, such as the fluoroquinolones resistance genes qnr. Freshwater appears to play an important role in the emergence and in the spread of antibiotic resistances, highlighting the necessity for strategies of water quality improvement. We assume that further knowledge is needed to better understand the role of the environment as reservoir of antibiotic resistances and to elucidate the link between environmental pollution by anthropogenic pressures and emergence of antibiotic resistances. Only an integrated vision of these two aspects can provide elements to assess the risk of spread of antibiotic resistances via water bodies and suggest, in this context, solutions for this urgent health issue. PMID- 22303297 TI - The genes and enzymes of phosphonate metabolism by bacteria, and their distribution in the marine environment. AB - Phosphonates are compounds that contain the chemically stable carbon-phosphorus (C-P) bond. They are widely distributed amongst more primitive life forms including many marine invertebrates and constitute a significant component of the dissolved organic phosphorus reservoir in the oceans. Virtually all biogenic C-P compounds are synthesized by a pathway in which the key step is the intramolecular rearrangement of phosphoenolpyruvate to phosphonopyruvate. However C-P bond cleavage by degradative microorganisms is catalyzed by a number of enzymes - C-P lyases, C-P hydrolases, and others of as-yet-uncharacterized mechanism. Expression of some of the pathways of phosphonate catabolism is controlled by ambient levels of inorganic P (Pi) but for others it is Pi independent. In this report we review the enzymology of C-P bond metabolism in bacteria, and also present the results of an in silico investigation of the distribution of the genes that encode the pathways responsible, in both bacterial genomes and in marine metagenomic libraries, and their likely modes of regulation. Interrogation of currently available whole-genome bacterial sequences indicates that some 10% contain genes encoding putative pathways of phosphonate biosynthesis while ~40% encode one or more pathways of phosphonate catabolism. Analysis of metagenomic data from the global ocean survey suggests that some 10 and 30%, respectively, of bacterial genomes across the sites sampled encode these pathways. Catabolic routes involving phosphonoacetate hydrolase, C-P lyase(s), and an uncharacterized 2-aminoethylphosphonate degradative sequence were predominant, and it is likely that both substrate-inducible and Pi-repressible mechanisms are involved in their regulation. The data we present indicate the likely importance of phosphonate-P in global biogeochemical P cycling, and by extension its role in marine productivity and in carbon and nitrogen dynamics in the oceans. PMID- 22303298 TI - Epigenomics - Grand Challenge: Much more than the Developmental Origins of Adult Health and Disease. PMID- 22303299 TI - A grand challenge for nutrigenomics. PMID- 22303300 TI - Grand Challenges and Opportunities in Deciphering the Role of Non-Coding RNAs in Human Diseases. PMID- 22303301 TI - The grand challenge for frontiers in genetics: to understand past, present, and future. PMID- 22303302 TI - Single Nucleotide Polymorphisms in the Insulin-Like Growth Factor 1 (IGF-1) Gene are Associated with Performance in Holstein-Friesian Dairy Cattle. AB - Insulin-like growth factor 1 (IGF-1) has been shown to be associated with fertility, growth, and development in cattle. The aim of this study was to (1) identify novel single nucleotide polymorphisms (SNPs) in the bovine IGF-1 gene and alongside previously identified SNPs (2) determine their association with traits of economic importance in Holstein-Friesian dairy cattle. Nine novel SNPs were identified across a panel of 22 beef and dairy cattle by sequence analysis of the 5' promoter, intronic, and 3' regulatory regions, encompassing ~5 kb of IGF-1. Genotyping and associations with daughter performance for milk production, fertility, survival, and measures of body size were undertaken on 848 Holstein Friesian AI sires. Using multiple regression analysis nominal associations (P < 0.05) were identified between six SNPs (four novel and two previously identified) and milk composition, survival, body condition score, and body size. The C allele of AF017143 a previously published SNP (C-512T) in the promoter region of IGF-1 predicted to introduce binding sites for transcription factors HSF1 and ZNF217 was associated (P < 0.05) with increased cow carcass weight (i.e., an indicator of mature cow size). Novel SNPs were identified in the 3' region of IGF-1 were associated (P < 0.05) with functional survival and chest width. The remaining four SNPs, all located within introns of IGF-1 were associated (P < 0.05) with milk protein yield, milk fat yield, milk fat concentration, somatic cell score, carcass conformation, and carcass fat. Results of this study further demonstrate the multifaceted influences of IGF-1 on milk production and growth related traits in cattle. PMID- 22303303 TI - A primer on high-throughput computing for genomic selection. AB - High-throughput computing (HTC) uses computer clusters to solve advanced computational problems, with the goal of accomplishing high-throughput over relatively long periods of time. In genomic selection, for example, a set of markers covering the entire genome is used to train a model based on known data, and the resulting model is used to predict the genetic merit of selection candidates. Sophisticated models are very computationally demanding and, with several traits to be evaluated sequentially, computing time is long, and output is low. In this paper, we present scenarios and basic principles of how HTC can be used in genomic selection, implemented using various techniques from simple batch processing to pipelining in distributed computer clusters. Various scripting languages, such as shell scripting, Perl, and R, are also very useful to devise pipelines. By pipelining, we can reduce total computing time and consequently increase throughput. In comparison to the traditional data processing pipeline residing on the central processors, performing general purpose computation on a graphics processing unit provide a new-generation approach to massive parallel computing in genomic selection. While the concept of HTC may still be new to many researchers in animal breeding, plant breeding, and genetics, HTC infrastructures have already been built in many institutions, such as the University of Wisconsin-Madison, which can be leveraged for genomic selection, in terms of central processing unit capacity, network connectivity, storage availability, and middleware connectivity. Exploring existing HTC infrastructures as well as general-purpose computing environments will further expand our capability to meet increasing computing demands posed by unprecedented genomic data that we have today. We anticipate that HTC will impact genomic selection via better statistical models, faster solutions, and more competitive products (e.g., from design of marker panels to realized genetic gain). Eventually, HTC may change our view of data analysis as well as decision-making in the post-genomic era of selection programs in animals and plants, or in the study of complex diseases in humans. PMID- 22303304 TI - Grand challenges in statistical genetics/genomics methodology. PMID- 22303306 TI - Circulating MicroRNAs as Minimally Invasive Biomarkers for Cancer Theragnosis and Prognosis. AB - Novel cancer biomarker discovery is urgently needed for cancer theragnosis and prognosis, and among the many possible types of samples, blood is regarded to be ideal for this discovery as it can be collected easily in a minimally invasive manner. Results of the past few years have ascertained the quantification of microRNA (miRNA) as a promising approach for the detection and prognostication of cancer. Indeed, an increasing number of studies have shown that circulating cancer-associated miRNAs are readily measured in plasma or serum and they can robustly discriminate cancer patients from healthy controls, as well as distinguishing between good-prognosis and poor-prognosis patients. Furthermore, recent findings also suggest the potential of circulating miRNAs in the screening, monitoring, and treatment of cancer. This article summarizes the most significant and latest discoveries of original researches on circulating miRNAs involvement in cancer, focusing on the potential of circulating miRNAs as minimally invasive biomarkers for cancer theragnosis and prognosis. PMID- 22303305 TI - Inferring Causation from Cross-Sectional Data: Examination of the Causal Relationship between Hyperactivity-Impulsivity and Novelty Seeking. AB - Previous research suggests an association between hyperactivity-impulsivity - one of the two behavioral dimensions that form attention deficit hyperactivity disorder - and the temperament characteristic of novelty seeking. We aimed to examine etiological links underlying the co-occurrence between these behaviors using a general population sample of 668 twin pairs, ages 7-10, for whom we obtained parent ratings in middle childhood; and pilot longitudinal data on 76 children. Structural equation modeling confirmed a shared genetic etiology (genetic correlation, r(D) = 0.81; 95% confidence intervals = 0.34-1.00) and showed that much (64%) of the covariation can be accounted for by shared genetic effects. In addition, causal paths were modeled between the two behaviors; 12% of the variance in novelty seeking at age 7 was accounted for by hyperactive impulsive behaviors at the same age. The causal effects model fits with the current characterization of hyperactive-impulsive behaviors reflecting a heightened need for stimulation. This has important implications for the management of hyperactive-impulsive behaviors in clinical settings. PMID- 22303307 TI - Non-Coding RNAs in Neural Networks, REST-Assured. AB - In the nervous system, several key steps in cellular complexity and development are regulated by non-coding RNAs (ncRNAs) and the repressor element-1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF). REST recruits gene regulatory complexes to regulatory sequences, among them the repressor element-1/neuron-restrictive silencer element, and mediates developmental stage-specific gene expression or repression, chromatin (re )organization or silencing for protein-coding genes as well as for several ncRNAs like microRNAs, short interfering RNAs or long ncRNAs. NcRNAs are far from being just transcriptional noise and are involved in chromatin accessibility, transcription and post-transcriptional processing, trafficking, or RNA editing. REST and its cofactor CoREST are both highly regulated through various ncRNAs. The importance of the correct regulation within the ncRNA network, the ncRNAome, is demonstrated when it comes to a deregulation of REST and/or ncRNAs associated with molecular pathophysiology underlying diverse disorders including neurodegenerative diseases or brain tumors. PMID- 22303309 TI - A grand challenge for applied genetic epidemiology: putting the human genome in context. PMID- 22303310 TI - Frontiers in toxicogenomics - the grand challenge: to understand how the genome and epigenome interact with the toxic environment. PMID- 22303308 TI - Grand challenge in behavioral and psychiatric genetics: quantitative challenges to keeping up with molecular advances. PMID- 22303311 TI - GRFT - Genetic Records Family Tree Web Applet. AB - Current software for storing and displaying records of genetic crosses does not provide an easy way to determine the lineage of an individual. The genetic records family tree (GRFT) applet processes records of genetic crosses and allows researchers to quickly visualize lineages using a family tree construct and to access other information from these records using any Internet browser. Users select from three display features: (1) a family tree view which displays a color coded family tree for an individual, (2) a sequential list of crosses, and (3) a list of crosses matching user-defined search criteria. Each feature contains options to specify the number of records shown and the latter two contain an option to filter results by the owner of the cross. The family tree feature is interactive, displaying a popup box with genetic information when the user mouses over an individual and allowing the user to draw a new tree by clicking on any individual in the current tree. The applet is written in JavaScript and reads genetic records from a tab-delimited text file on the server, so it is cross platform, can be accessed by anyone with an Internet connection, and supports almost instantaneous generation of new trees and table lists. Researchers can use the tool with their own genetic cross records for any sexually reproducing organism. No additional software is required and with only minor modifications to the script, researchers can add their own custom columns. GRFT's speed, versatility, and low overhead make it an effective and innovative visualization method for genetic records. A sample tool is available at http://stanford.edu/walbot/grft-sample.html. PMID- 22303313 TI - BDNF contributes to the genetic variance of milk fat yield in german holstein cattle. AB - The gene encoding the brain-derived neurotrophic factor (BDNF) has been repeatedly associated with human obesity. As such, it could also contribute to the regulation of energy partitioning and the amount of secreted milk fat during lactation, which plays an important role in milk production in dairy cattle. Therefore, we performed an association study using estimated breeding values (EBVs) of bulls and yield deviations of German Holstein dairy cattle to test the effect of BDNF on milk fat yield (FY). A highly significant effect (corrected p value = 3.362 * 10(-4)) was identified for an SNP 168 kb up-stream of the BDNF transcription start. The association tests provided evidence for an additive allele effect of 5.13 kg of fat per lactation on the EBV for milk FY in bulls and 6.80 kg of fat of the own production performance in cows explaining 1.72 and 0.60% of the phenotypic variance in the analyzed populations, respectively. The analyses of bulls and cows consistently showed three haplotype groups that differed significantly from each other, suggesting at least two different mutations in the BDNF region affecting the milk FY. The FY increasing alleles also had low but significant positive effects on protein and total milk yield which suggests a general role of the BDNF region in energy partitioning, rather than a specific regulation of fat synthesis. The results obtained in dairy cattle suggest similar effects of BDNF on milk composition in other species, including man. PMID- 22303312 TI - Nutrigenetics, nutrigenomics, and selenium. AB - Selenium (Se) is an important micronutrient that, as a component of selenoproteins, influences oxidative and inflammatory processes. Its' levels vary considerably, with different ethnic and geographic population groups showing varied conditions, ranging from frank Se deficiencies to toxic effects. An optimum Se level is essential for the maintenance of homeostasis, and this optimum may vary according to life stage, general state of health, and genotype. Nutrigenetic studies of different Se levels, in the presence of genetic variants in selenoproteins, suggest that an effective dietary Se intake for one individual may be very different from that for others. However, we are just starting to learn the significance of various genes in selenoprotein pathways, functional variants in these, and how to combine such data from genes into pathways, alongside dietary intake or serum levels of Se. Advances in systems biology, genetics, and genomics technologies, including genetic/genomic, epigenetic/epigenomic, transcriptomic, proteomic, and metabolomic information, start to make it feasible to assess a comprehensive spectrum of the biological activity of Se. Such nutrigenomic approaches may prove very sensitive biomarkers of optimal Se status at the individual or population level. The premature cessation of a major human Se intervention trial has led to considerable controversy as to the value of Se supplementation at the population level. New websites provide convenient links to current information on methodologies available for nutrigenetics and nutrigenomics. These new technologies will increasingly become an essential tool in optimizing the level of Se and other micronutrients for optimal health, in individuals and in population groups. However, definitive proof of such effects will require very large collaborative studies, international agreement on study design, and innovative approaches to data analysis. PMID- 22303314 TI - Identification of Carcass and Meat Quality QTL in an F(2) Duroc * Pietrain Pig Resource Population Using Different Least-Squares Analysis Models. AB - A three-generation resource population was constructed by crossing pigs from the Duroc and Pietrain breeds. In this study, 954 F(2) animals were used to identify quantitative trait loci (QTL) affecting carcass and meat quality traits. Based on results of the first scan analyzed with a line-cross (LC) model using 124 microsatellite markers and 510 F(2) animals, 9 chromosomes were selected for genotyping of additional markers. Twenty additional markers were genotyped for 954 F(2) animals and 20 markers used in the first scan were genotyped for 444 additional F(2) animals. Three different Mendelian models using least-squares for QTL analysis were applied for the second scan: a LC model, a half-sib (HS) model, and a combined LC and HS model. Significance thresholds were determined by false discovery rate (FDR). In total, 50 QTL using the LC model, 38 QTL using the HS model, and 3 additional QTL using the combined LC and HS model were identified (q < 0.05). The LC and HS models revealed strong evidence for QTL regions on SSC6 for carcass traits (e.g., 10th-rib backfat; q < 0.0001) and on SSC15 for meat quality traits (e.g., tenderness, color, pH; q < 0.01), respectively. QTL for pH (SSC3), dressing percent (SSC7), marbling score and moisture percent (SSC12), CIE a* (SSC16), and carcass length and spareribs weight (SSC18) were also significant (q < 0.01). Additional marker and animal genotypes increased the statistical power for QTL detection, and applying different analysis models allowed confirmation of QTL and detection of new QTL. PMID- 22303315 TI - Genome partitioning of genetic variation for milk production and composition traits in holstein cattle. AB - The objective of this study was to estimate the contribution of each autosome to genetic variation of milk yield, fat, and protein percentage and somatic cell score in Holstein cattle. Data on 2294 Holstein bulls genotyped for 39,557 autosomal markers were used. Three approaches were applied to estimate the proportion of genetic variance attributed to each chromosome. In two of them, marker-derived kinship coefficients were computed, using either marker genotypes observed on the whole genome or on subsets relative to each chromosome. Variance components were then estimated using residual maximum likelihood in method 1 or a regression-based approach in method 2. In method 3, genetic variances associated to each marker were estimated in a linear multiple regression approach, and then were summed up chromosome-wise. Generally, all chromosomes contributed to genetic variation. For most of the chromosomes, the amount of variance attributed to a chromosome was found to be proportional to its physical length. Nevertheless, for traits influenced by genes with very large effects a larger proportion of the genetic variance is expected to be associated with the chromosomes where these genes are. This is illustrated with the DGAT1 gene on BTA14 which is known to have a large effect on fat percentage in milk. The proportion of genetic variance for fat percentage associated with chromosome 14 was two to sevenfold (depending on the method) larger than would be predicted from chromosome size alone. Based on method 3 an approach is suggested to estimate the effective number of genes underlying the inheritance of the studied traits, yielding numbers between N ~ 400 (for fat percentage) to N ~ 900 (for milk yield). It is argued that these numbers are conservative lower bound estimates, but are in line with recent findings suggesting a highly polygenic background of production traits in dairy cattle. PMID- 22303316 TI - Association of porcine heparanase and hyaluronidase 1 and 2 with reproductive and production traits in a landrace-duroc-yorkshire population. AB - The ovary and placenta are dynamic structures requiring constant modification both structurally and through cell-cell communication capabilities. The extracellular matrix and basement membranes are primarily composed of a milieu of glycosaminoglycans, including heparan sulfate and hyaluronan. Heparanase (HPSE) and hyaluronidases (HYAL) are responsible for degrading heparan sulfate and hyaluronan, respectively. Therefore, the objective of this study was to evaluate the relationship of SNPs distinct to HPSE, HYAL1, and HYAL2 with measurements of reproduction and production traits in swine. Single trait associations were performed on a Landrace-Duroc-Yorkshire population using SNPs discovered and identified in HPSE, HYAL1, and HYAL2. Analyses were conducted on an extended pedigree and SNPs were found to be associated with reproductive and production traits. Prior to multiple-testing corrections, SNPs within HPSE were weakly associated (P < 0.03) having additive effects with age at puberty (-2.5 +/- 1.08 days), ovulation rate (0.5 +/- 0.24 corpora lutea), and number of piglets born alive (0.9 +/- 0.44 piglets). A HYAL1 and two HYAL2 SNP were nominally associated (P <= 0.0063) with number of piglets born alive after multiple-testing corrections (effects between 1.02 and 1.44 piglets), while one of the same HYAL2 markers maintained a modest association (P = 0.0043) having a dominant effect with number of piglets weaned (1.2 +/- 0.41 piglets) after multiple-testing correction. Functionally, HPSE and HYAL1 and 2 have been shown to participate in events related to ovarian and placental activity. SNPs from these studies could potentially assist with understanding genetic components underlying sow lifetime productivity as measured by piglet survivability based on number born alive and number weaned, thereby contributing to a greater number of pigs/sow/year. PMID- 22303317 TI - The Extended Nutrigenomics - Understanding the Interplay between the Genomes of Food, Gut Microbes, and Human Host. AB - Comprehensive investigation of nutritional health effects at the molecular level requires the understanding of the interplay between three genomes, the food, the gut microbial, and the human host genome. Food genomes are researched for discovery and exploitation of macro- and micronutrients as well as specific bioactives, with those genes coding for bioactive proteins and peptides being of central interest. The human gut microbiota encompasses a complex ecosystem in the intestine with profound impact on host metabolism. It is being studied at genomic and, more recently, also at proteomic and metabonomic level. Humans are being characterized at the level of genetic pre-disposition and inter-individual variability in terms of (i) response to nutritional interventions and direction of health trajectories; (ii) epigenetic, metabolic programming at certain life stages with health consequences later in life and even for subsequent generations; and (iii) acute genomic expression as a holistic response to diet, monitored at gene transcript, protein and metabolite level. Modern nutrition science explores health-related aspects of bioactive food components, thereby promoting health, preventing, or delaying the onset of disease, optimizing performance and assessing benefits and risks in individuals and subpopulations. Personalized nutrition means adapting food to individual needs, depending on the human host's life stage, -style, and -situation. Traditionally, nutrigenomics and nutri(epi)genetics are seen as the key sciences to understand human variability in preferences and requirements for diet as well as responses to nutrition. This article puts the three nutrition and health-relevant genomes into perspective, namely the food, the gut microbial and the human host's genome, and calls for an "extended nutrigenomics" approach in order to build the future tools for personalized nutrition, health maintenance, and disease prevention. We discuss examples of these genomes, proteomes, transcriptomes, and metabolomes under the definition of genomics as the overarching term covering essentially all Omics rather than the sole study of DNA and RNA. PMID- 22303318 TI - MicroRNAs: New Players in Multiple Myeloma. AB - MicroRNAs (miRNAs) are short non-coding RNAs that play critical roles in numerous cellular processes through post-transcriptional regulating functions. The aberrant role of miRNAs has been reported in a number of hematopoietic malignancies including multiple myeloma (MM). In this review we summarize the current knowledge on roles of miRNAs in the pathogenesis of MM. PMID- 22303319 TI - Effect of maternal and post-weaning folate supply on gene-specific DNA methylation in the small intestine of weaning and adult apc and wild type mice. AB - Increasing evidence supports the developmental origins of adult health and disease hypothesis which argues for a causal relationship between adverse early life nutrition and increased disease risk in adulthood. Modulation of epigenetic marks, e.g., DNA methylation and consequential altered gene expression, has been proposed as a mechanism mediating these effects. Via its role as a methyl donor, dietary folate supply may influence DNA methylation. As aberrant methylation is an early event in colorectal cancer (CRC) pathogenesis, we hypothesized low maternal and/or post-weaning folate intake may influence methylation of genes involved in CRC development. We investigated the effects of maternal folate depletion during pregnancy and lactation on selected gene methylation in the small intestine of wild type (WT) and Apc(+/Min) mice at weaning and as adults. We also investigated the effects of folate depletion post-weaning on gene methylation in adult mice. Female C57Bl6/J mice were fed low or normal folate diets from mating with Apc(+/Min) males to the end of lactation. A sub-set of offspring were killed at weaning. Remaining offspring were weaned on to low or normal folate diets, resulting in four treatment groups of Apc(+/Min) and WT mice. p53 was more methylated in weaning and adult WT compared with Apc(+/Min) mice (p > 0.001). Igf2 and Apc were hypermethylated in adult Apc(+/Min) compared with WT mice (p = 0.004 and 0.012 respectively). Low maternal folate reduced p53 methylation in adults (p = 0.04). Low post-weaning folate increased Apc methylation in Apc(+/Min) mice only (p = 0.008 for interaction). These observations demonstrate that folate depletion in early life can alter epigenetic marks in a gene-specific manner. Also, the differential effects of altered folate supply on DNA methylation in WT and Apc(+/Min) mice suggest that genotype may modulate epigenetic responses to environmental cues and may have implications for the development of personalized nutrition. PMID- 22303321 TI - Systematic Curation of miRBase Annotation Using Integrated Small RNA High Throughput Sequencing Data for C. elegans and Drosophila. AB - MicroRNAs (miRNAs) are a class of 20-23 nucleotide small RNAs that regulate gene expression post-transcriptionally in animals and plants. Annotation of miRNAs by the miRNA database (miRBase) has largely relied on computational approaches. As a result, many miRBase entries lack experimental validation, and discrepancies between miRBase annotation and actual miRNA sequences are often observed. In this study, we integrated the small RNA sequencing (smRNA-seq) datasets in Caenorhabditis elegans and Drosophila melanogaster and devised an analytical pipeline coupled with detailed manual inspection to curate miRNA annotation systematically in miRBase. Our analysis reveals 19 (17.0%) and 51 (31.3%) miRNAs entries with detectable smRNA-seq reads have mature sequence discrepancies in C. elegans and D. melanogaster, respectively. These discrepancies frequently occur either for conserved miRNA families whose mature sequences were predicted according to their homologous counterparts in other species or for miRNAs whose precursor miRNA (pre-miRNA) hairpins produce an abundance of multiple miRNA isoforms or variants. Our analysis shows that while Drosophila pre-miRNAs, on average, produce less than 60% accurate mature miRNA reads in addition to their 5' and 3' variant isoforms, the precision of miRNA processing in C. elegans is much higher, at over 90%. Based on the revised miRNA sequences, we analyzed expression patterns of the more conserved (MC) and less conserved (LC) miRNAs and found that, whereas MC miRNAs are often co-expressed at multiple developmental stages, LC miRNAs tend to be expressed specifically at fewer stages. PMID- 22303320 TI - The obesity epidemic: from the environment to epigenetics - not simply a response to dietary manipulation in a thermoneutral environment. AB - The prevalence of obesity continues to increase particularly in developed countries. To establish the primary mechanisms involved, relevant animal models which track the developmental pathway to obesity are required. This need is emphasized by the substantial rise in the number of overweight and obese children, of which a majority will remain obese through adulthood. The past half century has been accompanied with unprecedented transitions in our lifestyle. Each of these changes substantially contributes to enhancing our capacity to store energy into adipose tissues. The complex etiology of adiposity is critical as a majority of models investigating obesity utilize a simplistic high-fat/low carbohydrate diet, fed over a short time period to comparatively young inbred animals maintained in fixed environment. The natural history of obesity is much more complex involving many other mechanisms and this type of challenge may not be the optimal experimental intervention. Such processes include changes in adipose tissue composition with time and the transition from brown to white adipose tissue. Brown adipose tissue, due its unique ability to rapidly produce large amounts of heat could have a pivotal role in energy balance and is under epigenetic regulation mediated by the histone H3k9-specific demethylase Jhdma2a. Furthermore, day length has a potential role in determining endocrine and metabolic responses in brown fat. The potential to utilize novel models and interventions across a range of animal species in adipose tissue development may finally start to yield sustainable strategies by which excess fat mass can, at last, be avoided in humans. PMID- 22303322 TI - Frontiers in genomic assay technologies: the grand challenges in enabling data intensive biological research. PMID- 22303323 TI - Developmental programming in response to maternal overnutrition. AB - Metabolic disorders have seen an increased prevalence in recent years in developed as well as developing countries. While it is clear lifestyle choices and habits have contributed to this epidemic, mounting evidence suggests the nutritional milieu during critical stages of development in early life can "program" individuals to develop the metabolic syndrome later in life. Extensive epidemiological data presents an association between maternal obesity and nutrition during pregnancy and offspring obesity, and a number of animal models have been established in order to uncover the underlying mechanisms contributing to the programming of physiological systems. It is hard to distinguish the causal factors due to the complex nature of the maternal-fetal relationship; however, in order to develop adequate prevention strategies it is vital to identify which maternal factor(s) - be it the diet, diet-induced obesity or weight gain - and at which time during early development instigate the programmed phenotype. Curtailing the onset of obesity at this early stage in life presents a promising avenue through which to stem the growing epidemic of obesity. PMID- 22303324 TI - Epigenetic memory in mammals. AB - Epigenetic information can be passed on from one generation to another via DNA methylation, histone modifications, and changes in small RNAs, a process called epigenetic memory. During a mammal's lifecycle epigenetic reprogramming, or the resetting of most epigenetic marks, occurs twice. The first instance of reprogramming occurs in primordial germ cells and the second occurs following fertilization. These processes may be both passive and active. In order for epigenetic inheritance to occur the epigenetic modifications must be able to escape reprogramming. There are several examples supporting this non-Mendelian mechanism of inheritance including the prepacking of early developmental genes in histones instead of protamines in sperm, genomic imprinting via methylation marks, the retention of CenH3 in mammalian sperm and the inheritance of piwi associated interfering RNAs. The ability of mammals to pass on epigenetic information to their progeny provides clear evidence that inheritance is not restricted to DNA sequence and epigenetics plays a key role in producing viable offspring. PMID- 22303326 TI - Between genes and genomes - future challenges for cytogenetics. PMID- 22303327 TI - Cost-effective prediction of gender-labeling errors and estimation of gender labeling error rates in candidate-gene association studies. AB - We describe a statistical approach to predict gender-labeling errors in candidate gene association studies, when Y-chromosome markers have not been included in the genotyping set. The approach adds value to methods that consider only the heterozygosity of X-chromosome SNPs, by incorporating available information about the intensity of X-chromosome SNPs in candidate genes relative to autosomal SNPs from the same individual. To our knowledge, no published methods formalize a framework in which heterozygosity and relative intensity are simultaneously taken into account. Our method offers the advantage that, in the genotyping set, no additional space is required beyond that already assigned to X-chromosome SNPs in the candidate genes. We also show how the predictions can be used in a two-phase sampling design to estimate the gender-labeling error rates for an entire study, at a fraction of the cost of a conventional design. PMID- 22303325 TI - Systems Biology Reveals MicroRNA-Mediated Gene Regulation. AB - MicroRNAs (miRNAs) are members of the small non-coding RNAs, which are principally known for their functions as post-transcriptional regulators of target genes. Regulation by miRNAs is triggered by the translational repression or degradation of their complementary target messenger RNAs (mRNAs). The growing number of reported miRNAs and the estimate that hundreds or thousands of genes are regulated by them suggest a magnificent gene regulatory network in which these molecules are embedded. Indeed, recent reports have suggested critical roles for miRNAs in various biological functions, such as cell differentiation, development, oncogenesis, and the immune responses, which are mediated by systems wide changes in gene expression profiles. Therefore, it is essential to analyze this complex regulatory network at the transcriptome and proteome levels, which should be possible with approaches that include both high-throughput experiments and computational methodologies. Here, we introduce several systems-level approaches that have been applied to miRNA research, and discuss their potential to reveal miRNA-guided gene regulatory systems and their impacts on biological functions. PMID- 22303328 TI - Dark matter: are mice the solution to missing heritability? AB - Genome-wide association studies (GWAS) in humans have identified hundreds of single nucleotide polymorphisms associated with complex traits, yet for most traits studied, the sum total of all these identified variants fail to explain a significant portion of the heritable variation. Reasons for this "missing heritability" are thought to include the existence of rare causative variants not captured by current genotyping arrays, structural variants that go undetected by existing technology, insufficient power to identify multi-gene interactions, small sample sizes, and the influence of environmental and epigenetic effects. As genotyping technologies have evolved it has become inexpensive and relatively straightforward to perform GWAS in mice. Mice offer a powerful tool for elucidating the genetic architecture of behavioral and physiological traits, and are complementary to human studies. Unlike F(2) crosses of inbred strains, advanced intercross lines, heterogeneous stocks, outbred, and wild-caught mice have more rapid breakdown of linkage disequilibrium which allow for increasingly high resolution mapping. Because some of these populations are created using a small number of founder chromosomes they are not expected to harbor rare alleles. We discuss the differences between these mouse populations and examine their potential to overcome some of the pitfalls that have plagued human GWAS studies. PMID- 22303329 TI - Serotonin Transporter (5-HTTLPR) Genotype and Childhood Trauma are Associated with Individual Differences in Decision Making. AB - The factors that influence individual differences in decision making are not yet fully characterized, but convergent evidence is accumulating that implicates serotonin (5-HT) system function. Therefore, both genes and environments that influence serotonin function are good candidates for association with risky decision making. In the present study we examined associations between common polymorphisms in the serotonin transporter gene (SLC6A4; 5-HTTLPR and rs25531), the experience of childhood trauma and decision making on the Iowa gambling task (IGT) in 391 (64.5% female) healthy Caucasian adults. Homozygosity for the 5 HTTLPR L allele was associated with riskier decision making in the first block of 20 trials (i.e., decision making under ambiguity, p = 0.004). In addition, mean IGT performance was significantly worse in blocks 3-5 (i.e., decision making under risk, p <= 0.05) for those participants who reported experiencing higher levels of childhood trauma. Our findings add to the growing evidence that genetic variation in the 5-HT system is associated with individual differences in decision making under ambiguity; and we report that the experience of childhood trauma is associated with relatively poor decision making under risk. PMID- 22303330 TI - Grand challenge in livestock genomics: for food, for medicine, for the environment, for knowledge. PMID- 22303331 TI - Modeling Equilibrium of microRNA Expression. AB - MicroRNAs are a class of non-coding RNAs and the dysregulated expression of these short RNA molecules was frequently observed in cancer cells. The steady state level of microRNA concentration may differentiate the biological function of the cells between normal and impaired. To understand the steady state or equilibrium of microRNAs, their interactions with transcription factors and target genes need to be explored and visualized through prediction and network analysis algorithms. This article discusses the application of mathematical model for simulating the dynamics of network feedback loop so as to decipher the mechanism of microRNA regulation. PMID- 22303332 TI - Mthfs is an Essential Gene in Mice and a Component of the Purinosome. AB - Tetrahydrofolates (THF) are a family of cofactors that function as one-carbon donors in folate-dependent one-carbon metabolism, a metabolic network required for the de novo synthesis of purines, thymidylate, and for the remethylation of homocysteine to methionine in the cytoplasm. 5-FormylTHF is not a cofactor in one carbon metabolism, but serves as a storage form of THF cofactors. 5-formylTHF is mobilized back into the THF cofactor pool by methenyltetrahydrofolate synthetase (MTHFS), which catalyzes the irreversible and ATP-dependent conversion 5 formyltetrahydrofolate to 5,10-methenyltetrahydrofolate. Mthfs is not an essential gene in Arabidopsis, but MTHFS expression is elevated in animal tumors, enhances de novo purine synthesis, confers partial resistance to antifolate purine synthesis inhibitors and increases rates of folate catabolism in mammalian cell cultures. However, the mechanisms underlying these effects of MTHFS expression have yet to be established. The purpose of this study was to investigate the role and essentiality of MTHFS in mice. Mthfs was disrupted through the insertion of a gene trap vector between exons 1 and 2. Mthfs(gt/+) mice were fertile and viable. No Mthfs(gt/gt) embryos were recovered from Mthfs(gt/+) intercrosses, indicating Mthfs is an essential gene in mice. Tissue MTHFS protein levels are decreased in both Mthfs(gt/+) and Mthfs(+/+) mice placed on a folate and choline deficient diet, and mouse embryonic fibroblasts from Mthfs(gt/+) embryos exhibit decreased capacity for de novo purine synthesis without impairment in de novo thymidylate synthesis. MTHFS was shown to co localize with two enzymes of the de novo purine synthesis pathway in HeLa cells in a cell cycle-dependent manner, and to be modified by the small ubiquitin-like modifier (SUMO) protein. Mutation of the consensus SUMO modification sites on MTHFS eliminated co-localization of MTHFS with the de novo purine biosynthesis pathway under purine-deficient conditions. The results from this study indicate that MTHFS enhances purine biosynthesis by delivering 10-formylTHF to the purinosome in a SUMO-dependent fashion. PMID- 22303333 TI - Replication of GWAS "Hits" by Race for Breast and Prostate Cancers in European Americans and African Americans. AB - In this study, we assessed association of genome-wide association studies (GWAS) "hits" by race with adjustment for potential population stratification (PS) in two large, diverse study populations; the Carolina Breast Cancer Study (CBCS; N total = 3693 individuals) and the University of Pennsylvania Study of Clinical Outcomes, Risk, and Ethnicity (SCORE; N total = 1135 individuals). In both study populations, 136 ancestry information markers and GWAS "hits" (CBCS: FGFR2, 8q24; SCORE: JAZF1, MSMB, 8q24) were genotyped. Principal component analysis was used to assess ancestral differences by race. Multivariable unconditional logistic regression was used to assess differences in cancer risk with and without adjustment for the first ancestral principal component (PC1) and for an interaction effect between PC1 and the GWAS "hit" (SNP) of interest. PC1 explained 53.7% of the variance for CBCS and 49.5% of the variance for SCORE. European Americans and African Americans were similar in their ancestral structure between CBCS and SCORE and cases and controls were well matched by ancestry. In the CBCS European Americans, 9/11 SNPs were significant after PC1 adjustment, but after adjustment for the PC1 by SNP interaction effect, only one SNP remained significant (rs1219648 in FGFR2); for CBCS African Americans, 6/11 SNPs were significant after PC1 adjustment and after adjustment for the PC1 by SNP interaction effect, all six SNPs remained significant and an additional SNP now became significant. In the SCORE European Americans, 0/9 SNPs were significant after PC1 adjustment and no changes were seen after additional adjustment for the PC1 by SNP interaction effect; for SCORE African Americans, 2/9 SNPs were significant after PC1 adjustment and after adjustment for the PC1 by SNP interaction effect, only one SNP remained significant (rs16901979 at 8q24). We show that genetic associations by race are modified by interaction between individual SNPs and PS. PMID- 22303334 TI - The application and performance of single nucleotide polymorphism markers for population genetic analyses of lepidoptera. AB - Microsatellite markers are difficult to apply within lepidopteran studies due to the lack of locus-specific PCR amplification and the high proportion of "null" alleles, such that erroneous estimations of population genetic parameters often result. Herein single nucleotide polymorphism (SNP) markers are developed from Ostrinia nubilalis (Lepidoptera: Crambidae) using next generation expressed sequence tag (EST) data. A total of 2742 SNPs were predicted within a reference assembly of 7414 EST contigs, and a subset of 763 were incorporated into 24 multiplex PCR reactions. To validate this pipeline, 5 European and North American sample sites were genotyped at 178 SNP loci, which indicated 84 (47.2%) were in Hardy-Weinberg equilibrium. Locus-by-locus F(ST), analysis of molecular variance, and STRUCTURE analyses indicate significant genetic differentiation may exist between European and North American O. nubilalis. The observed genetic diversity was significantly lower among European sites, which may result from genetic drift, natural selection, a genetic bottleneck, or ascertainment bias due to North American origin of EST sequence data. SNPs are an abundant source of mutation data for molecular genetic marker development in non-model species, with shared ancestral SNPs showing application within closely related species. These markers offer advantages over microsatellite markers for genetic and genomic analyses of Lepidoptera, but the source of mutation data may affect the estimation of population parameters and likely need to be considered in the interpretation of empirical data. PMID- 22303335 TI - MIRNA-DISTILLER: A Stand-Alone Application to Compile microRNA Data from Databases. AB - MicroRNAs (miRNA) are small non-coding RNA molecules of ~22 nucleotides which regulate large numbers of genes by binding to seed sequences at the 3' untranslated region of target gene transcripts. The target mRNA is then usually degraded or translation is inhibited, although thus resulting in posttranscriptional down regulation of gene expression at the mRNA and/or protein level. Due to the bioinformatic difficulties in predicting functional miRNA binding sites, several publically available databases have been developed that predict miRNA binding sites based on different algorithms. The parallel use of different databases is currently indispensable, but highly uncomfortable and time consuming, especially when working with numerous genes of interest. We have therefore developed a new stand-alone program, termed MIRNA-DISTILLER, which allows to compile miRNA data for given target genes from public databases. Currently implemented are TargetScan, microCosm, and miRDB, which may be queried independently, pairwise, or together to calculate the respective intersections. Data are stored locally for application of further analysis tools including freely definable biological parameter filters, customized output-lists for both miRNAs and target genes, and various graphical facilities. The software, a data example file and a tutorial are freely available at http://www.ikp stuttgart.de/content/language1/html/10415.asp. PMID- 22303336 TI - Optimization of gene-assisted selection in small-sized populations: comparison of deterministic and stochastic approaches. AB - Many of the models used to optimize selection processes in livestock make the assumption that the population is of infinite size and are built on deterministic equations. The finite size case should however be considered explicitly when selection involves one identified gene. Indeed, drift can cause the loss of a favorable allele if its initial frequency is low. In this paper, a stochastic approach was developed to simultaneously optimize selection on two traits in a limited size population: a quantitative trait with underlying polygenic variation and a monogenic trait. We outline the interests of considering the limited size of the population in stochastic modeling with a simple example. Such stochastic models raise some technical problems (uncertain convergence to the maximum, computational burden) which could obliterate their usefulness as compared to simpler but approximate deterministic models which can be used when the population size is large. By way of this simple example, we show the feasibility of the optimization of this type of model using a genetic algorithm and demonstrate its interest compared with the corresponding deterministic model which assumes that the population is of infinite size. PMID- 22303337 TI - Pathway-Wide Association Study Implicates Multiple Sterol Transport and Metabolism Genes in HDL Cholesterol Regulation. AB - Pathway-based association methods have been proposed to be an effective approach in identifying disease genes, when single-marker association tests do not have sufficient power. The analysis of quantitative traits may be benefited from these approaches, by sampling from two extreme tails of the distribution. Here we tested a pathway association approach on a small genome-wide association study (GWAS) on 653 subjects with extremely high high-density lipoprotein cholesterol (HDL-C) levels and 784 subjects with low HDL-C levels. We identified 102 genes in the sterol transport and metabolism pathways that collectively associate with HDL C levels, and replicated these association signals in an independent GWAS. Interestingly, the pathways include 18 genes implicated in previous GWAS on lipid traits, suggesting that genuine HDL-C genes are highly enriched in these pathways. Additionally, multiple biologically relevant loci in the pathways were not detected by previous GWAS, including genes implicated in previous candidate gene association studies (such as LEPR, APOA2, HDLBP, SOAT2), genes that cause Mendelian forms of lipid disorders (such as DHCR24), and genes expressing dyslipidemia phenotypes in knockout mice (such as SOAT1, PON1). Our study suggests that sampling from two extreme tails of a quantitative trait and examining genetic pathways may yield biological insights from smaller samples than are generally required using single-marker analysis in large-scale GWAS. Our results also implicate that functionally related genes work together to regulate complex quantitative traits, and that future large-scale studies may benefit from pathway-association approaches to identify novel pathways regulating HDL-C levels. PMID- 22303338 TI - Peripheral blood RNA expression profiling in illicit methcathinone users reveals effect on immune system. AB - Methcathinone (ephedrone) is relatively easily accessible for abuse. Its users develop an extrapyramidal syndrome and it is not known if this is caused by methcathinone itself, by side-ingredients (manganese), or both. In the present study we aimed to clarify molecular mechanisms underlying this condition. We used microarrays to analyze whole-genome gene expression patterns of peripheral blood from 20 methcathinone users and 20 matched controls. Gene expression profile data were analyzed by Bayesian modeling and functional annotation. Of 28,869 genes on the microarrays, 326 showed statistically significant differential expression with FDR adjusted p-values below 0.05. Quantitative real-time PCR confirmed differential expression for the most of the genes selected for validation. Functional annotation and network analysis indicated activation of a gene network that included immunological disease, cellular movement, and cardiovascular disease functions (enrichment score 42). As HIV and HCV infections were confounding factors, we performed additional stratification of subjects. A similar functional activation of the "immunological disease" category was evident when we compared subjects according to injection status (past versus current users, balanced for HIV and HCV infection). However, this difference was not large therefore the major effect was related to the HIV status of the subjects. Mn-methcathinone abusers have blood RNA expression patterns that mostly reflect their HIV and HCV infections. PMID- 22303339 TI - Use of Genome Sequence Information for Meat Quality Trait QTL Mining for Causal Genes and Mutations on Pig Chromosome 17. AB - The newly available pig genome sequence has provided new information to fine map quantitative trait loci (QTL) in order to eventually identify causal variants. With targeted genomic sequencing efforts, we were able to obtain high quality BAC sequences that cover a region on pig chromosome 17 where a number of meat quality QTL have been previously discovered. Sequences from 70 BAC clones were assembled to form an 8-Mbp contig. Subsequently, we successfully mapped five previously identified QTL, three for meat color and two for lactate related traits, to the contig. With an additional 25 genetic markers that were identified by sequence comparison, we were able to carry out further linkage disequilibrium analysis to narrow down the genomic locations of these QTL, which allowed identification of the chromosomal regions that likely contain the causative variants. This research has provided one practical approach to combine genetic and molecular information for QTL mining. PMID- 22303341 TI - Differential effects of krill oil and fish oil on the hepatic transcriptome in mice. AB - Dietary supplementation with omega-3 polyunsaturated fatty acids (omega-3 PUFAs), specifically the fatty acids docosahexaenoic acid (DHA; 22:6 omega-3) and eicosapentaenoic acid (EPA; 20:5 omega-3), is known to have beneficial health effects including improvements in glucose and lipid homeostasis and modulation of inflammation. To evaluate the efficacy of two different sources of omega-3 PUFAs, we performed gene expression profiling in the liver of mice fed diets supplemented with either fish oil (FO) or krill oil (KO). We found that omega-3 PUFA supplements derived from a phospholipid krill fraction (KO) downregulated the activity of pathways involved in hepatic glucose production as well as lipid and cholesterol synthesis. The data also suggested that KO-supplementation increases the activity of the mitochondrial respiratory chain. Surprisingly, an equimolar dose of EPA and DHA derived from FO modulated fewer pathways than a KO supplemented diet and did not modulate key metabolic pathways regulated by KO, including glucose metabolism, lipid metabolism and the mitochondrial respiratory chain. Moreover, FO upregulated the cholesterol synthesis pathway, which was the opposite effect of krill-supplementation. Neither diet elicited changes in plasma levels of lipids, glucose, or insulin, probably because the mice used in this study were young and were fed a low-fat diet. Further studies of KO supplementation using animal models of metabolic disorders and/or diets with a higher level of fat may be required to observe these effects. PMID- 22303340 TI - Genome Scan for Parent-of-Origin QTL Effects on Bovine Growth and Carcass Traits. AB - Parent-of-origin effects (POE) such as genomic imprinting influence growth and body composition in livestock, rodents, and humans. Here, we report the results of a genome scan to detect quantitative trait loci (QTL) with POE on growth and carcass traits in Angus * Brahman cattle crossbreds. We identified 24 POE-QTL on 15 Bos taurus autosomes (BTAs) of which six were significant at 5% genome-wide (GW) level and 18 at the 5% chromosome-wide (CW) significance level. Six QTL were paternally expressed while 15 were maternally expressed. Three QTL influencing post-weaning growth map to the proximal end of BTA2 (linkage region of 0-9 cM; genomic region of 5.0-10.8 Mb), for which only one imprinted ortholog is known so far in the human and mouse genomes, and therefore may potentially represent a novel imprinted region. The detected QTL individually explained 1.4 ~ 5.1% of each trait's phenotypic variance. Comparative in silico analysis of bovine genomic locations show that 32 out of 1,442 known mammalian imprinted genes from human and mouse homologs map to the identified QTL regions. Although several of the 32 genes have been associated with quantitative traits in cattle, only two (GNAS and PEG3) have experimental proof of being imprinted in cattle. These results lend additional support to recent reports that POE on quantitative traits in mammals may be more common than previously thought, and strengthen the need to identify and experimentally validate cattle orthologs of imprinted genes so as to investigate their effects on quantitative traits. PMID- 22303342 TI - SOAPsplice: Genome-Wide ab initio Detection of Splice Junctions from RNA-Seq Data. AB - RNA-Seq, a method using next generation sequencing technologies to sequence the transcriptome, facilitates genome-wide analysis of splice junction sites. In this paper, we introduce SOAPsplice, a robust tool to detect splice junctions using RNA-Seq data without using any information of known splice junctions. SOAPsplice uses a novel two-step approach consisting of first identifying as many reasonable splice junction candidates as possible, and then, filtering the false positives with two effective filtering strategies. In both simulated and real datasets, SOAPsplice is able to detect many reliable splice junctions with low false positive rate. The improvement gained by SOAPsplice, when compared to other existing tools, becomes more obvious when the depth of sequencing is low. SOAPsplice is freely available at http://soap.genomics.org.cn/soapsplice.html. PMID- 22303343 TI - A Grand Challenge in Evolutionary and Population Genetics: New Paradigms for Exploring the Past and Charting the Future in the Post-Genomic era. PMID- 22303344 TI - Maternal omega-3 supplementation increases fat mass in male and female rat offspring. AB - Adipogenesis and lipogenesis are highly sensitive to the nutritional environment in utero and in early postnatal life. Omega-3 long chain polyunsaturated fatty acids (LCPUFA) inhibit adipogenesis and lipogenesis in adult rats, however it is not known whether supplementing the maternal diet with omega-3 LCPUFA results in reduced fat deposition in the offspring. Female Albino Wistar rats were fed either a standard chow (Control, n = 10) or chow designed to provide ~15 mg/kg/day of omega-3 LCPUFA, chiefly as docosahexaenoic acid (DHA), throughout pregnancy and lactation (Omega-3, n = 11) and all pups were weaned onto a commercial rat chow. Blood and tissues were collected from pups at 3 and 6 weeks of age and weights of visceral and subcutaneous fat depots recorded. The expression of adipogenic and lipogenic genes in the subcutaneous and visceral fat depots were determined using quantitative real time reverse transcription-PCR. Birth weight and postnatal growth were not different between groups. At 6 weeks of age, total percentage body fat was significantly increased in both male (5.09 +/- 0.32% vs. 4.56 +/- 0.2%, P < 0.04) and female (5.15 +/- 0.37% vs. 3.89 +/- 0.36%, P < 0.04) offspring of omega-3 dams compared to controls. The omega-3 LCPUFA content of erythrocyte phospholipids (as a% of total fatty acids) was higher in omega-3 offspring (6.7 +/- 0.2% vs. 5.6 +/- 0.2%, P < 0.001). There was no effect of maternal omega-3 LCPUFA supplementation on the expression of adipogenic or lipogenic genes in the offspring in either the visceral or subcutaneous fat depots. We have therefore established that an omega-3 rich environment during pregnancy and lactation in a rodent model increases fat accumulation in both male and female offspring, particularly in subcutaneous depots, but that this effect is not mediated via upregulation adipogenic/lipogenic gene transcription. These data suggest that maternal n-3 LCPUFA supplementation during pregnancy/lactation may not be an effective strategy for reducing fat deposition in the offspring. PMID- 22303345 TI - A Parallel Study of mRNA and microRNA Profiling of Peripheral Blood in Young Adult Women. AB - BACKGROUND: Aging is a complex process that involves the interplay of genetic, epigenetic, and environmental factors. Identifying aging-related biomarkers holds great potential for improving our understanding of complex physiological changes, thereby providing a means to investigate the mechanism by which aging influences various diseases. METHOD AND RESULTS: We performed a parallel study of microRNA and gene expression profiling of peripheral blood in a group of healthy young adult women, among which 13 were aged 22-25 and 9 were aged 36-39 years old. We identified a significantly distinct pattern of microRNA, but not gene expression profiling, between these two young adult women groups. We also performed correlation analysis of expression levels between all pairs of age-associated microRNAs and genes and identified a weak global correlation between these two types of expression levels. A significant involvement of estrogen regulation was observed by pathway analysis of the most differentially expressed microRNAs that included miR-155, -18a, -142, -340, -363, -195, and -24. CONCLUSION: Our results suggest that the change in global microRNA expression in the peripheral blood is associated with normal aging in young adult women. This change may precede global gene expression changes. Future studies are needed to investigate the regulatory mechanism of the estrogen-related microRNAs and associated diseases. PMID- 22303346 TI - Clusters of adaptive evolution in the human genome. AB - Considerable work has been devoted to identifying regions of the human genome that have been subjected to recent positive selection. Although detailed follow up studies of putatively selected regions are critical for a deeper understanding of human evolutionary history, such studies have received comparably less attention. Recently, we have shown that ALMS1 has been the target of recent positive selection acting on standing variation in Eurasian populations. Here, we describe a careful follow-up analysis of genetic variation across the ALMS1 region, which unexpectedly revealed a cluster of substrates of positive selection. Specifically, through the analysis of SNP data from the HapMap and Human Genome Diversity Project-Centre d'Etude du Polymorphisme Humain samples as well sequence data from the region, we find compelling evidence for three independent and distinct signals of recent positive selection across this 3 Mb region surrounding ALMS1. Moreover, we analyzed the HapMap data to identify other putative clusters of independent selective events and conservatively discovered 19 additional clusters of adaptive evolution. This work has important implications for the interpretation of genome-scans for positive selection in humans and more broadly contributes to a better understanding of how recent positive selection has shaped genetic variation across the human genome. PMID- 22303347 TI - Estimating allele frequency from next-generation sequencing of pooled mitochondrial DNA samples. AB - BACKGROUND: Both common and rare mitochondrial DNA (mtDNA) variants may contribute to genetic susceptibility to some complex human diseases. Understanding of the role of mtDNA variants will provide valuable insights into the etiology of these diseases. However, to date, there have not been any large scale, genome-wide association studies of complete mtDNA variants and disease risk. One reason for this might be the substantial cost of sequencing the large number of samples required for genetic epidemiology studies. Next-generation sequencing of pooled mtDNA samples will dramatically reduce the cost of such studies and may represent an appealing approach for large-scale genetic epidemiology studies. However, the performance of the different designs of sequencing pooled mtDNA has not been evaluated. METHODS: We examined the approach of sequencing pooled mtDNA of multiple individuals for estimating allele frequency using the Illumina genome analyzer (GA) II sequencing system. In this study the pool included mtDNA samples of 20 subjects that had been sequenced previously using Sanger sequencing. Each pool was replicated once to assess variation of the sequencing error between pools. To reduce such variation, barcoding was used for sequencing different pools in the same lane of the flow cell. To evaluate the effect of different pooling strategies pooling was done at both the pre- and post-PCR amplification step. RESULTS: The sequencing error rate was close to that expected based on the Phred score. When only reads with Phred >= 20 were considered, the average error rate was about 0.3%. However, there was significant variation of the base-calling errors for different types of bases or at different loci. Using the results of the Sanger sequencing as the standard, the sensitivity of single nucleotide polymorphism detection with post-PCR pooling (about 99%) was higher than that of the pre-PCR pooling (about 82%), while the two approaches had similar specificity (about 99%). Among a total of 298 variants in the sample, the allele frequencies of 293 variants (98%) were correctly estimated with post-PCR pooling, the correlation between the estimated and the true allele frequencies being >0.99, while only 206 allele frequencies (69%) were correctly estimated in the pre-PCR pooling, the correlation being 0.89. CONCLUSION: Sequencing of mtDNA pooled after PCR amplification is a viable tool for screening mitochondrial variants potentially related to human diseases. PMID- 22303348 TI - Perinatal exogenous nitric oxide in fawn-hooded hypertensive rats reduces renal ribosomal biogenesis in early life. AB - Nitric oxide (NO) is known to depress ribosome biogenesis in vitro. In this study we analyzed the influence of exogenous NO on ribosome biogenesis in vivo using a proven antihypertensive model of perinatal NO administration in genetically hypertensive rats. Fawn-hooded hypertensive rat (FHH) dams were supplied with the NO-donor molsidomine in drinking water from 2 weeks before to 4 weeks after birth, and the kidneys were subsequently collected from 2 day, 2 week, and 9 to 10-month-old adult offspring. Although the NO-donor increased maternal NO metabolite excretion, the NO status of juvenile renal (and liver) tissue was unchanged as assayed by EPR spectroscopy of NO trapped with iron-dithiocarbamate complexes. Nevertheless, microarray analysis revealed marked differential up regulation of renal ribosomal protein genes at 2 days and down-regulation at 2 weeks and in adult males. Such differential regulation of renal ribosomal protein genes was not observed in females. These changes were confirmed in males at 2 weeks by expression analysis of renal ribosomal protein L36a and by polysome profiling, which also revealed a down-regulation of ribosomes in females at that age. However, renal polysome profiles returned to normal in adults after early exposure to molsidomine. No direct effects of molsidomine were observed on cellular proliferation in kidneys at any age, and the changes induced by molsidomine in renal polysome profiles at 2 weeks were absent in the livers of the same rats. Our results suggest that the previously found prolonged antihypertensive effects of perinatal NO administration may be due to epigenetically programmed alterations in renal ribosome biogenesis during a critical fetal period of renal development, and provide a salient example of a drug-induced reduction of ribosome biogenesis that is accompanied by a beneficial long-term health effect in both males and females. PMID- 22303349 TI - Origins of maize: a further paradox resolved. PMID- 22303350 TI - Improved measurements of RNA structure conservation with generalized centroid estimators. AB - Identification of non-protein-coding RNAs (ncRNAs) in genomes is a crucial task for not only molecular cell biology but also bioinformatics. Secondary structures of ncRNAs are employed as a key feature of ncRNA analysis since biological functions of ncRNAs are deeply related to their secondary structures. Although the minimum free energy (MFE) structure of an RNA sequence is regarded as the most stable structure, MFE alone could not be an appropriate measure for identifying ncRNAs since the free energy is heavily biased by the nucleotide composition. Therefore, instead of MFE itself, several alternative measures for identifying ncRNAs have been proposed such as the structure conservation index (SCI) and the base pair distance (BPD), both of which employ MFE structures. However, these measurements are unfortunately not suitable for identifying ncRNAs in some cases including the genome-wide search and incur high false discovery rate. In this study, we propose improved measurements based on SCI and BPD, applying generalized centroid estimators to incorporate the robustness against low quality multiple alignments. Our experiments show that our proposed methods achieve higher accuracy than the original SCI and BPD for not only human-curated structural alignments but also low quality alignments produced by CLUSTAL W. Furthermore, the centroid-based SCI on CLUSTAL W alignments is more accurate than or comparable with that of the original SCI on structural alignments generated with RAF, a high quality structural aligner, for which twofold expensive computational time is required on average. We conclude that our methods are more suitable for genome-wide alignments which are of low quality from the point of view on secondary structures than the original SCI and BPD. PMID- 22303351 TI - Gender-Specific Hierarchy in Nuage Localization of PIWI-Interacting RNA Factors in Drosophila. AB - PIWI-interacting RNAs (piRNAs) are germline-specific small non-coding RNAs that form piRNA-induced silencing complexes (piRISCs) by associating with PIWI proteins, a subclade of the Argonaute proteins predominantly expressed in the germline. piRISCs protect the integrity of the germline genome from invasive transposable DNA elements by silencing them. Multiple piRNA biogenesis factors have been identified in Drosophila. The majority of piRNA factors are localized in the nuage, electron-dense non-membranous cytoplasmic structures located in the perinuclear regions of germ cells. Thus, piRNA biogenesis is thought to occur in the nuage in germ cells. Immunofluorescence analyses of ovaries from piRNA factor mutants have revealed a localization hierarchy of piRNA factors in female nuage. However, whether this hierarchy is female-specific or can also be applied in male gonads remains undetermined. Here, we show by immunostaining of both ovaries and testes from piRNA factor mutants that the molecular hierarchy of piRNA factors shows gender-specificity, especially for Krimper (Krimp), a Tudor-domain containing protein of unknown function(s): Krimp is dispensable for PIWI protein Aubergine (Aub) nuage localization in ovaries but Krimp and Aub require each other for their proper nuage localization in testes. This suggests that the functional requirement of Krimp in piRNA biogenesis may be different in male and female gonads. PMID- 22303352 TI - Mechanisms involved in the selective transfer of long chain polyunsaturated Fatty acids to the fetus. AB - The concentration of long chain polyunsaturated fatty acid (LCPUFA) in the fetal brain increases dramatically from the third trimester until 18 months of life. Several studies have shown an association between the percentage of maternal plasma docosahexaenoic acid (DHA) during gestation and development of cognitive functions in the neonate. Since only very low levels of LCPUFA are synthesized in the fetus and placenta, their primary source for the fetus is the maternal circulation. Both in vitro and human in vivo studies using labeled fatty acids have shown preferential transfer of LCPUFA from the placenta to the fetus compared with other fatty acids, although the mechanisms involved are still uncertain. The placenta takes up circulating maternal non-esterified fatty acids (NEFA) and fatty acids released mainly by maternal lipoprotein lipase and endothelial lipase. These NEFA may enter the cell by passive diffusion or by means of membrane carrier proteins. Once in the cytosol, NEFA bind to cytosolic fatty acid-binding proteins for transfer to the fetal circulation or can be oxidized within the trophoblasts, and even re-esterified and stored in lipid droplets. Although trophoblast cells are not specialized for lipid storage, LCPUFA may up-regulate peroxisome proliferator activated receptor-gamma (PPARgamma) and hence the gene expression of fatty acid transport carriers, fatty acid acyl-CoA-synthetases and adipophilin or other enzymes involved in lipolysis, modifying the rate of placental transfer, and metabolism. The placental transfer of LCPUFA during pregnancy seems to be a key factor in the neurological development of the fetus. Increased knowledge of the factors that modify placental transfer of fatty acids would contribute to our understanding of this complex process. PMID- 22303353 TI - MicroRNA Control of Invasion and Metastasis Pathways. AB - Despite recent advances, cancer remains a leading cause of death worldwide. In developed countries, the incidence of colorectal and breast cancer has been stable, but no improvement in prognosis has been observed if the patient presents with metastases at diagnosis. This fact highlights the importance of therapeutic approaches targeting cellular invasion and metastasis programs as the next step in cancer treatment. During carcinoma progression a process called epithelial mesenchymal transition (EMT) results in enhanced invasion and motility which is directly linked with loss of epithelial polarity and epithelial junctions, migration permissive cytoskeleton alterations, and the acquisition of mesenchymal properties. The recent discovery of microRNAs (miRNAs) controlling key cellular pathways has opened a new era in understanding how EMT pathways are modulated. In this review, we classify EMT regulating proteins according to their cellular localization (membrane, cytoplasmic, and nuclear), and summarize the current knowledge on how they are controlled by miRNAs and propose potential miRNAs for the transcripts that may control their expression. PMID- 22303354 TI - The quantitative genetics of phenotypic error or uniformity. PMID- 22303355 TI - Grand challenges in bioinformatics and computational biology. PMID- 22303356 TI - Aorta Measurements are Heritable and Influenced by Bicuspid Aortic Valve. AB - OBJECTIVES: To determine whether the contributions of genetics and bicuspid aortic valve (BAV) independently influence aortic (Ao) dimensions. BACKGROUND: Ao dilation is a risk factor for aneurysm, dissection, and sudden cardiac death. Frequent association of BAV with Ao dilation implicates a common underlying defect possibly due to genetic factors. METHODS: Families enriched for BAV underwent standardized transthoracic echocardiography. In addition to BAV status, echocardiographic measures of Ao (annulus to descending Ao), pulmonary artery, and mitral valve annulus (MVA) diameters were obtained. Using variance components analysis, heritability was estimated with and without BAV status. Additionally, bivariate genetic analyses between Ao dimensions and BAV were performed. RESULTS: Our cohort was obtained from 209 families enriched for BAV. After adjusting for age, body surface area, and sex, individuals with BAV had a statistically significant increase in all echocardiographic measurements (p < 0.006) except descending Ao and MVA. Individuals with BAV were at greater odds of having Ao dilation (OR = 4.44, 95% CI 2.93-6.72) than family members without BAV. All echocardiographic measurements exhibited moderate to strong heritability (0.25 0.53), and these estimates were not influenced by inclusion of BAV as a covariate. Bivariate genetic analyses supported that the genetic correlation between BAV and echo measures were not significantly different from zero. CONCLUSION: We show for the first time that echocardiographic measurements of Ao, pulmonary artery and MVA diameters are quantitative traits that exhibit significant heritability. In addition, our results suggest the presence of BAV independently influences the proximal Ao and pulmonary artery measures but not those in the descending Ao or MVA. PMID- 22303357 TI - MicroRNAs as New Characters in the Plot between Epigenetics and Prostate Cancer. AB - Prostate cancer (PCA) still represents a leading cause of death. An increasing number of studies have documented that microRNAs (miRNAs), a subgroup of non coding RNAs with gene regulatory functions, are differentially expressed in PCA respect to the normal tissue counterpart, suggesting their involvement in prostate carcinogenesis and dissemination. Interestingly, it has been shown that miRNAs undergo the same regulatory mechanisms than any other protein coding gene, including epigenetic regulation. In turn, miRNAs can also affect the expression of oncogenes and tumor suppressor genes by targeting effectors of the epigenetic machinery, therefore indirectly affecting the epigenetic controls on these genes. Among the genes that undergo this complex regulation, there is the androgen receptor (AR), a key therapeutic target for PCA. This review will focus on the role of epigenetically regulated and epigenetically regulating miRNAs in PCA and on the fine regulation of AR expression, as mediated by this miRNA-epigenetics interaction. PMID- 22303358 TI - A narrow quantitative trait locus in C. elegans coordinately affects longevity, thermotolerance, and resistance to paraquat. AB - By linkage mapping of quantitative trait loci, we previously identified at least 11 natural genetic variants that significantly modulate Caenorhabditis elegans life-span (LS), many of which would have eluded discovery by knock-down or mutation screens. A region on chromosome IV between markers stP13 and stP35 had striking effects on longevity in three inter-strain crosses (each P < 10(-9)). In order to define the limits of that interval, we have now constructed two independent lines by marker-based selection during 20 backcross generations, isolating the stP13-stP35 interval from strain Bergerac-BO in a CL2a background. These congenic lines differed significantly from CL2a in LS, assayed in two environments (each P < 0.001). We then screened for exchange of flanking markers to isolate recombinants that partition this region, because fine-mapping the boundaries for overlapping heteroallelic spans can greatly narrow the implicated interval. Recombinants carrying the CL2a allele at stP35 were consistently long lived compared to those retaining the Bergerac-BO allele (P < 0.001), and more resistant to temperature elevation and paraquat (each ~1.7-fold, P < 0.0001), but gained little protection from ultraviolet or peroxide stresses. Two rounds of recombinant screening, followed by fine-mapping of break-points and survival testing, narrowed the interval to 0.18 Mb (13.35-13.53 Mb) containing 26 putative genes and six small-nuclear RNAs - a manageable number of targets for functional assessment. PMID- 22303359 TI - Dystrophin Orchestrates the Epigenetic Profile of Muscle Cells Via miRNAs. AB - Mammalian musculature is a very robust and dynamic tissue that goes through many rounds of degeneration and regeneration in an individual's lifetime. There is a biological program that maintains muscle progenitor cells that, when activated, give rise to intermediate myoblast progeny that consequently differentiate into mature muscle cells. Recent works have provided a picture of the role that microRNAs (miRNAs) play in maintaining aspects of this program. Intriguingly, a subset of these miRNAs is de-regulated in muscular dystrophies (MDs), a group of fatal inherited neuromuscular disorders that are often associated with deficiencies in the Dystrophin (Dys) complex. Apparently, transcriptional expression of many of the muscle specific genes and miRNAs is dependent on chromatin state regulated by the Dys-Syn-nNOS pathway. This puts Dystrophin at the epicenter of a highly regulated program of muscle gene expression in which miRNAs help to coordinate networking between multiple phases of muscle maintenance, degeneration, and regeneration. Therefore, understanding the role of miRNAs in physiology of normal and diseased muscle tissue could be useful for future applications in improving the MD therapies and could open new clinical perspectives. PMID- 22303360 TI - The functional consequences of relative substrate specificity in complex biochemical systems. AB - A biochemical activity, that is, enzymatic reaction or molecular interaction, frequently involves a molecule, for example, an enzyme, capable of interacting with numerous substrates or partners. Specificity is a fundamental property of biochemical activities, and relative specificity refers to the situation whereby a molecule interacts with multiple substrates or partners but with different affinities. Here, a hypothesis is proposed that any molecule, such as an enzyme, would have a range of preferences or relative specificity for its many native substrates, which differentially impacts the phenotypes of these substrates and hence shapes the relevant biological processes in vivo. While the mechanisms underlying the specific recognition between enzymes and individual substrates have been studied extensively, whether any enzyme exhibits intrinsic selectivity toward its ensemble of substrates is often overlooked, and whether this selectivity has any functional consequences is much less appreciated. There are, however, several lines of evidence in the literature that are consistent with the hypothesis and reviewed here. Furthermore, this hypothesis is supported by our analyses of a number of diverse biochemical systems at a large scale. Thus, the human microRNA processing machinery possesses relative specificity toward its hundreds of substrates, which might contribute to differential microRNA biogenesis; the promoter binding affinity of the transcription factor Ndt80 might regulate Ndt80 target mRNA expression in the budding yeast; Cdk1 kinase specificity might lead to variable substrate phosphorylation in vivo; and the density of HuR deposition to its thousands of RNA targets might partly explain differential RNA expression in human cells. It is proposed, therefore, that relative specificity is a universal property of complex biochemical systems and that the hypothesis could denote a general principle in biology. PMID- 22303361 TI - MicroRNAs in Hepatobiliary and Pancreatic Cancers. AB - MicroRNAs (miRNAs) are small non-coding RNAs that function as endogenous silencers of numerous target genes. Hundreds of miRNAs have been identified in the human genome. miRNAs are expressed in a tissue-specific manner and play important roles in cell proliferation, apoptosis, and differentiation. Aberrant expression of miRNAs may also contribute to the development and progression of human hepatobiliary and pancreatic cancers. Recent studies have shown that some miRNAs play roles as tumor suppressors or oncogenes in hepatobiliary and pancreatic cancers. miR-122, let-7 family, and miR-101 are down-regulated in hepatocellular carcinoma (HCC), suggesting that it is a potential tumor suppressor of HCC. miR-221 and miR-222 are up-regulated in HCC and may act as oncogenic miRNAs in hepatocarcinogenesis. miRNA expression profiling may be a powerful clinical tool for diagnosis and regulation of miRNA expression could be a novel therapeutic strategy for hepatobiliary and pancreatic cancers. In this review, we summarize current knowledge about the roles of important tumor suppressor microRNAs and oncogenic microRNAs in hepatobiliary and pancreatic cancers. PMID- 22303362 TI - Epigenomics of ovarian cancer and its chemoprevention. AB - Ovarian cancer is a major cause of death among gynecological cancers and its etiology is still unclear. Currently, the two principle obstacles in treating this life threatening disease are lack of effective biomarkers for early detection and drug resistance after initial chemotherapy. Similar to other cancers, the initiation and development of ovarian cancer is characterized by disruption of oncogenes and tumor suppressor genes by both genetic and epigenetic mechanisms. While it is well known that it is challenging to treat ovarian cancer through a genetic strategy due in part to its heterogeneity, the reversibility of epigenetic mechanisms involved in ovarian cancer opens exciting new avenues for treatment. The epigenomics of ovarian cancer has therefore become a rapidly expanding field leading to intense investigation. A review on the current status of the field is thus warranted. In this analysis, we will evaluate the current status of epigenomics of ovarian cancer and will include epigenetic mechanisms involved in ovarian cancer development such as DNA methylation, histone modifications, and non-coding microRNA. Development of biomarkers, the epigenetic basis for drug resistance and improved chemotherapy for ovarian cancer will also be assessed. In addition, the potential use of natural compounds as epigenetic modulators in chemotherapy shows promise in moving to the forefront of ovarian cancer treatment strategies. PMID- 22303363 TI - We're All Computational Biologists Now...Next Stop, the Global Brain? PMID- 22303364 TI - Molecular evolution of the non-coding eosinophil granule ontogeny transcript. AB - Eukaryotic genomes are pervasively transcribed. A large fraction of the transcriptional output consists of long, mRNA-like, non-protein-coding transcripts (mlncRNAs). The evolutionary history of mlncRNAs is still largely uncharted territory. In this contribution, we explore in detail the evolutionary traces of the eosinophil granule ontogeny transcript (EGOT), an experimentally confirmed representative of an abundant class of totally intronic non-coding transcripts (TINs). EGOT is located antisense to an intron of the ITPR1 gene. We computationally identify putative EGOT orthologs in the genomes of 32 different amniotes, including orthologs from primates, rodents, ungulates, carnivores, afrotherians, and xenarthrans, as well as putative candidates from basal amniotes, such as opossum or platypus. We investigate the EGOT gene phylogeny, analyze patterns of sequence conservation, and the evolutionary conservation of the EGOT gene structure. We show that EGO-B, the spliced isoform, may be present throughout the placental mammals, but most likely dates back even further. We demonstrate here for the first time that the whole EGOT locus is highly structured, containing several evolutionary conserved, and thermodynamic stable secondary structures. Our analyses allow us to postulate novel functional roles of a hitherto poorly understood region at the intron of EGO-B which is highly conserved at the sequence level. The region contains a novel ITPR1 exon and also conserved RNA secondary structures together with a conserved TATA-like element, which putatively acts as a promoter of an independent regulatory element. PMID- 22303365 TI - Gene expression: sizing it all up. AB - Genomic architecture appears to be a largely unexplored component of gene expression. That architecture can be related to chromatin domains, transposable element neighborhoods, epigenetic modifications of the genome, and more. Although surely not the end of the story, we are learning that when it comes to gene expression, size is also important. We have been surprised to find that certain patterns of expression, tissue specific versus constitutive, or high expression versus low expression, are often associated with physical attributes of the gene and genome. Multiple studies have shown an inverse relationship between gene expression patterns and various physical parameters of the genome such as intron size, exon size, intron number, and size of intergenic regions. An increase in expression level and breadth often correlates with a decrease in the size of physical attributes of the gene. Three models have been proposed to explain these relationships. Contradictory results were found in several organisms when expression level and expression breadth were analyzed independently. However, when both factors were combined in a single study a novel relationship was revealed. At low levels of expression, an increase in expression breadth correlated with an increase in genic, intergenic, and intragenic sizes. Contrastingly, at high levels of expression, an increase in expression breadth inversely correlated with the size of the gene. In this article we explore the several hypotheses regarding genome physical parameters and gene expression. PMID- 22303366 TI - Sex-, diet-, and cancer-dependent epistatic effects on complex traits in mice. AB - The genetic basis of quantitative traits such as body weight and obesity is complex, with several hundred quantitative trait loci (QTLs) known to affect these and related traits in humans and mice. It also has become increasingly evident that the single-locus effects of these QTLs vary considerably depending on factors such as the sex of the individuals and their dietary environment, and we were interested to know whether this context-dependency also applies to two locus epistatic effects of QTLs as well. We therefore conducted a genome scan to search for epistatic effects on 13 different weight and adiposity traits in an F(2) population of mice (created from an original intercross of the FVB strain with M16i, a polygenic obesity model) that were fed either a control or a high fat diet and half of which harbored a transgene (PyMT) that caused the development of metastatic mammary cancer. We used a conventional interval mapping approach with SNPs to scan all 19 autosomes, and found extensive epistasis affecting all of these traits. More importantly, we also discovered that the majority of these epistatic effects exhibited significant interactions with sex, diet, and/or presence of PyMT. Analysis of these interactions showed that many of them appeared to involve QTLs previously identified as affecting these traits, but whose single-locus effects were variously modified by two-locus epistatic effects of other QTLs depending on the sex, diet, or PyMT environment. It was concluded that this context-dependency of epistatic effects is an important component of the genetic architecture of complex traits such as those contributing to weight and obesity. PMID- 22303367 TI - Epitope-based immunoinformatics and molecular docking studies of nucleocapsid protein and ovarian tumor domain of crimean-congo hemorrhagic Fever virus. AB - Crimean-Congo hemorrhagic fever virus (CCHFV), the fatal human pathogen is transmitted to humans by tick bite, or exposure to infected blood or tissues of infected livestock. The CCHFV genome consists of three RNA segments namely, S, M, and L. The unusual large viral L protein has an ovarian tumor (OTU) protease domain located in the N terminus. It is likely that the protein may be autoproteolytically cleaved to generate the active virus L polymerase with additional functions. Identification of the epitope regions of the virus is important for the diagnosis, phylogeny studies, and drug discovery. Early diagnosis and treatment of CCHF infection is critical to the survival of patients and the control of the disease. In this study, we undertook different in silico approaches using molecular docking and immunoinformatics tools to predict epitopes which can be helpful for vaccine designing. Small molecule ligands against OTU domain and protein-protein interaction between a viral and a host protein have been studied using docking tools. PMID- 22303368 TI - Multilocus genetic analysis of brain images. AB - The quest to identify genes that influence disease is now being extended to find genes that affect biological markers of disease, or endophenotypes. Brain images, in particular, provide exquisitely detailed measures of anatomy, function, and connectivity in the living brain, and have identified characteristic features for many neurological and psychiatric disorders. The emerging field of imaging genomics is discovering important genetic variants associated with brain structure and function, which in turn influence disease risk and fundamental cognitive processes. Statistical approaches for testing genetic associations are not straightforward to apply to brain images because the data in brain images is spatially complex and generally high dimensional. Neuroimaging phenotypes typically include 3D maps across many points in the brain, fiber tracts, shape based analyses, and connectivity matrices, or networks. These complex data types require new methods for data reduction and joint consideration of the image and the genome. Image-wide, genome-wide searches are now feasible, but they can be greatly empowered by sparse regression or hierarchical clustering methods that isolate promising features, boosting statistical power. Here we review the evolution of statistical approaches to assess genetic influences on the brain. We outline the current state of multivariate statistics in imaging genomics, and future directions, including meta-analysis. We emphasize the power of novel multivariate approaches to discover reliable genetic influences with small effect sizes. PMID- 22303370 TI - Validity and power of missing data imputation for extreme sampling and terminal measures designs in mediation analysis. AB - Several authors have acknowledged that testing mediational hypotheses between treatments, genes, physiological measures, and behaviors may substantially advance our understanding of how these associations operate. In psychiatric research, the costs of measuring the putative mediator or the outcome can be prohibitive. Extreme sampling designs have been validated as methods for reducing study costs by increasing power per subject measured on the more expensive variable when assessing bivariate relationships. However, there exist concerns about how missing data can potentially bias the results. Additionally, most mediation analysis techniques presuppose the joint measurement of mediators and outcomes for all subjects. There have been limited methodological developments for techniques that can evaluate putative mediators in studies that have employed extreme sampling, resulting in missing data. We demonstrate that extreme (selective) sampling strategies can be beneficial in the context of mediation analyses. Handling the missing data with maximum likelihood (ML) resulted in minimal power loss and unbiased parameter estimates. We must be cautious, though, in recommending the ML approach for extreme sampling designs because it yielded inflated Type 1 error rates under some null conditions. Yet, the use of extreme sampling designs and methods to handle the resultant missing data presents a viable research strategy. PMID- 22303369 TI - DNA methylation: a timeline of methods and applications. AB - DNA methylation is a biochemical process where a DNA base, usually cytosine, is enzymatically methylated at the 5-carbon position. An epigenetic modification associated with gene regulation, DNA methylation is of paramount importance to biological health and disease. Recently, the quest to unravel the Human Epigenome commenced, calling for a modernization of previous DNA methylation profiling techniques. Here, we describe the major developments in the methodologies used over the past three decades to examine the elusive epigenome (or methylome). The earliest techniques were based on the separation of methylated and unmethylated cytosines via chromatography. The following years would see molecular techniques being employed to indirectly examine DNA methylation levels at both a genome-wide and locus-specific context, notably immunoprecipitation via anti-5'methylcytosine and selective digestion with methylation-sensitive restriction endonucleases. With the advent of sodium bisulfite treatment of DNA, a deamination reaction that converts cytosine to uracil only when unmethylated, the epigenetic modification can now be identified in the same manner as a DNA base-pair change. More recently, these three techniques have been applied to more technically advanced systems such as DNA microarrays and next-generation sequencing platforms, bringing us closer to unveiling a complete human epigenetic profile. PMID- 22303371 TI - Heritability of problem drinking and the genetic overlap with personality in a general population sample. AB - This study examined the heritability of problem drinking and investigated the phenotypic and genetic relationships between problem drinking and personality. In a sample of 5,870 twins and siblings and 4,420 additional family members from the Netherlands Twin Register. Data on problem drinking (assessed with the AUDIT and CAGE; 12 items) and personality [NEO Five-Factor Inventory (FFI); 60 items] were collected in 2009/2010 by surveys. Confirmatory factor analysis on the AUDIT and CAGE items showed that the items clustered on two separate but highly correlated (r = 0.74) underlying factors. A higher-order factor was extracted that reflected those aspects of problem drinking that are common to the AUDIT and CAGE, which showed a heritability of 40%. The correlations between problem drinking and the five dimensions of personality were small but significant, ranging from 0.06 for Extraversion to -0.12 for Conscientiousness. All personality dimensions (with broad-sense heritabilities between 32 and 55%, and some evidence for non-additive genetic influences) were genetically correlated with problem drinking. The genetic correlations were small to modest (between |0.12| and |0.41|). Future studies with longitudinal data and DNA polymorphisms are needed to determine the biological mechanisms that underlie the genetic link between problem drinking and personality. PMID- 22303372 TI - Hybrid Modeling of Cell Signaling and Transcriptional Reprogramming and Its Application in C. elegans Development. AB - Modeling of signal driven transcriptional reprogramming is critical for understanding of organism development, human disease, and cell biology. Many current modeling techniques discount key features of the biological sub-systems when modeling multiscale, organism-level processes. We present a mechanistic hybrid model, GESSA, which integrates a novel pooled probabilistic Boolean network model of cell signaling and a stochastic simulation of transcription and translation responding to a diffusion model of extracellular signals. We apply the model to simulate the well studied cell fate decision process of the vulval precursor cells (VPCs) in C. elegans, using experimentally derived rate constants wherever possible and shared parameters to avoid overfitting. We demonstrate that GESSA recovers (1) the effects of varying scaffold protein concentration on signal strength, (2) amplification of signals in expression, (3) the relative external ligand concentration in a known geometry, and (4) feedback in biochemical networks. We demonstrate that setting model parameters based on wild type and LIN-12 loss-of-function mutants in C. elegans leads to correct prediction of a wide variety of mutants including partial penetrance of phenotypes. Moreover, the model is relatively insensitive to parameters, retaining the wild-type phenotype for a wide range of cell signaling rate parameters. PMID- 22303373 TI - A grand challenge for genetics of aging: adding healthy years to our lives. PMID- 22303374 TI - Multifactor dimensionality reduction as a filter-based approach for genome wide association studies. AB - Advances in genotyping technology and the multitude of genetic data available now provide a vast amount of data that is proving to be useful in the quest for a better understanding of human genetic diseases through the study of genetic variation. This has led to the development of approaches such as genome wide association studies (GWAS) designed specifically for interrogating variants across the genome for association with disease, typically by testing single locus, univariate associations. More recently it has been accepted that epistatic (interaction) effects may also be great contributors to these genetic effects, and GWAS methods are now being applied to find epistatic effects. The challenge for these methods still remain in prioritization and interpretation of results, as it has also become standard for initial findings to be independently investigated in replication cohorts or functional studies. This is motivating the development and implementation of filter-based approaches to prioritize variants found to be significant in a discovery stage for follow-up for replication. Such filters must be able to detect both univariate and interactive effects. In the current study we present and evaluate the use of multifactor dimensionality reduction (MDR) as such a filter, with simulated data and a wide range of effect sizes. Additionally, we compare the performance of the MDR filter to a similar filter approach using logistic regression (LR), the more traditional approach used in GWAS analysis, as well as evaporative cooling (EC)-another prominent machine learning filtering method. The results of our simulation study show that MDR is an effective method for such prioritization, and that it can detect main effects, and interactions with or without marginal effects. Importantly, it performed as well as EC and LR for main effect models. It also significantly outperforms LR for various two-locus epistatic models, while it has equivalent results as EC for the epistatic models. The results of this study demonstrate the potential of MDR as a filter to detect gene-gene interactions in GWAS studies. PMID- 22303375 TI - Packaging of Non-Coding RNAs into Herpesvirus Virions: Comparisons to Coding RNAs. AB - The herpesviruses are a family of large DNA viruses capable of establishing lifelong infections. Recent reports have shown that herpesviruses package non coding RNA into virions; this follows earlier observations showing that coding RNAs are detected in virions. Packaging RNAs allows for their function immediately after virus entry and in the absence of de novo transcription. Despite the collective understanding that RNAs are packaged into herpesvirus virions, many questions remain. This review will highlight what is known regarding packaged coding and non-coding RNAs and discuss their potential impact to virus biology. PMID- 22303376 TI - Fine Mapping of Loci on BTA2 and BTA26 Associated with Bovine Viral Diarrhea Persistent Infection and Linked with Bovine Respiratory Disease in Cattle. AB - Bovine respiratory disease (BRD) is considered to be the most costly infectious disease in the cattle industry. Bovine viral diarrhea virus (BVDV) is one of the pathogens involved with the BRD complex of disease. BVDV infection also negatively impacts cow reproduction and calf performance. Loci associated with persistently infected animals (BVD-PI) and linked with BRD have previously been identified near 14 Mb on bovine chromosome 2 (BTA2) and 15.3 Mb on bovine chromosome 26 (BTA26). The objective of this study was to refine the loci associated with BVD-PI and linked with BRD. Association testing for BVD-PI was performed on a population of 65 BVD-PI calves, 51 of their dams, and 60 unaffected calves (controls) with 142 single nucleotide polymorphisms (SNPs) on BTA2 and 173 SNPs on BTA26. Comparisons were made between BVD-PI calves and controls calves and the dams of BVD-PI calves and controls calves. For the linkage analysis of BRD, the same markers were used to genotype two half-sib families consisting of the sires and 72 BRD positive and 148 BRD negative offspring. Using an allelic chi-square test, 11 loci on BTA2 and 8 loci on BTA26 were associated with the dams of the BVD-PI calves (P < 0.05) and 4 loci on BTA2 and 11 loci on BTA26 were associated with BVD-PI calves. This demonstrates that although some of the loci on BTA2 and BTA26 are jointly involved in the fetal and dam response to BVD-PI infection, there are loci that are solely associated with the maternal or fetal susceptibility to disease. One locus on BTA2 and two loci on BTA26 were found to be linked (P < 0.05) with BRD. The regions linked with BRD were also associated with BVD-PI demonstrating that both the broad (BRD) and narrow (BVD-PI) definition of disease identified shared genomic regions as important in disease susceptibility. These results further refined the loci associated with BVD-PI and linked with BRD. PMID- 22303377 TI - Tests of selection in pooled case-control data: an empirical study. AB - For smaller organisms with faster breeding cycles, artificial selection can be used to create sub-populations with different phenotypic traits. Genetic tests can be employed to identify the causal markers for the phenotypes, as a precursor to engineering strains with a combination of traits. Traditional approaches involve analyzing crosses of inbred strains to test for co-segregation with genetic markers. Here we take advantage of cheaper next generation sequencing techniques to identify genetic signatures of adaptation to the selection constraints. Obtaining individual sequencing data is often unrealistic due to cost and sample issues, so we focus on pooled genomic data. We explore a series of statistical tests for selection using pooled case (under selection) and control populations. The tests generally capture skews in the scaled frequency spectrum of alleles in a region, which are indicative of a selective sweep. Extensive simulations are used to show that these approaches work well for a wide range of population divergence times and strong selective pressures. Control vs control simulations are used to determine an empirical False Positive Rate, and regions under selection are determined using a 1% FPR level. We show that pooling does not have a significant impact on statistical power. The tests are also robust to reasonable variations in several different parameters, including window size, base-calling error rate, and sequencing coverage. We then demonstrate the viability (and the challenges) of one of these methods in two independent Drosophila populations (Drosophila melanogaster) bred under selection for hypoxia and accelerated development, respectively. Testing for extreme hypoxia tolerance showed clear signals of selection, pointing to loci that are important for hypoxia adaptation. Overall, we outline a strategy for finding regions under selection using pooled sequences, then devise optimal tests for that strategy. The approaches show promise for detecting selection, even several generations after fixation of the beneficial allele has occurred. PMID- 22303379 TI - On detecting selective sweeps using single genomes. AB - Identifying the genetic basis of human adaptation has remained a central focal point of modern population genetics. One major area of interest has been the use of polymorphism data to detect so-called "footprints" of selective sweeps - patterns produced as a beneficial mutation arises and rapidly fixes in the population. Based on numerous simulation studies and power analyses, the necessary sample size for achieving appreciable power has been shown to vary from a few individuals to a few dozen, depending on the test statistic. And yet, the sequencing of multiple copies of a single region, or of multiple genomes as is now often the case, incurs considerable cost. Enard et al. (2010) have recently proposed a method to identify patterns of selective sweeps using a single genome and apply this approach to human and non-human primates (chimpanzee, orangutan, and macaque). They employ essentially a modification of the Hudson, Kreitman, and Aguade test - using heterozygous single nucleotide polymorphisms from single individuals, and divergence data from two closely related species (human chimpanzee, human-orangutan, and human-macaque). Given the potential importance of this finding, we here investigate the properties of this statistic. We demonstrate through simulation that this approach is neither robust to demography nor background selection; nor is it robust to variable recombination rates. PMID- 22303378 TI - Epigenomics in environmental health. AB - This review considers the emerging relationships between environmental factors and epigenetic alterations and the application of genome-wide assessments to better define these relationships. First we will briefly cover epigenetic programming in development, one-carbon metabolism, and exposures that may disrupt normal developmental programming of epigenetic states. In addition, because a large portion of epigenetic research has focused on cancer, we discuss exposures associated with carcinogenesis including asbestos, alcohol, radiation, arsenic, and air pollution. Research on other exposures that may affect epigenetic states such as endocrine disruptors is also described, and we also review the evidence for epigenetic alterations associated with aging that may reflect cumulative effects of exposures. From this evidence, we posit potential mechanisms by which exposures modify epigenetic states, noting that understanding the true effect of environmental exposures on the human epigenome will require additional research with appropriate epidemiologic studies and application of novel technologies. With a more comprehensive understanding of the affects of exposures on the epigenome, including consideration of genetic background, the prediction of the toxic potential of new compounds may be more readily achieved, and may lead to the development of more personalized disease prevention and treatment strategies. PMID- 22303380 TI - A comparison of association methods for cytotoxicity mapping in pharmacogenomics. AB - Cytotoxicity assays of immortalized lymphoblastoid cell lines (LCLs) represent a promising new in vitro approach in pharmacogenomics research. However, previous studies employing LCLs in gene mapping have used simple association methods, which may not adequately capture the true differences in non-linear response profiles between genotypes. Two common approaches summarize each dose-response curve with either the IC50 or the slope parameter estimates from a hill slope fit and treat these estimates as the response in a linear model. The current study investigates these two methods, as well as four novel methods, and compares their power to detect differences between the response profiles of genotypes under a variety of different alternatives. The four novel methods include two methods that summarize each dose-response by its area under the curve, one method based off of an analysis of variance (ANOVA) design, and one method that compares hill slope fits for all individuals of each genotype. The power of each method was found to depend not only on the choice of alternative, but also on the choice for the set of dosages used in cytotoxicity measurements. The ANOVA-based method was found to be the most robust across alternatives and dosage sets for power in detecting differences between genotypes. PMID- 22303381 TI - Genetics of fat storage in flies and worms: what went wrong? PMID- 22303382 TI - Comparison of clustering methods for investigation of genome-wide methylation array data. AB - The use of genome-wide methylation arrays has proved very informative to investigate both clinical and biological questions in human epigenomics. The use of clustering methods either for exploration of these data or to compare to an a priori grouping, e.g., normal versus disease allows assessment of groupings of data without user bias. However no consensus on the methods to use for clustering of methylation array approaches has been reached. To determine the most appropriate clustering method for analysis of illumina array methylation data, a collection of data sets was simulated and used to compare clustering methods. Both hierarchical clustering and non-hierarchical clustering methods (k-means, k medoids, and fuzzy clustering algorithms) were compared using a range of distance and linkage methods. As no single method consistently outperformed others across different simulations, we propose a method to capture the best clustering outcome based on an additional measure, the silhouette width. This approach produced a consistently higher cluster accuracy compared to using any one method in isolation. PMID- 22303383 TI - Functional themes from psychiatric genome-wide screens. AB - Technological advances and a greater degree of inter-laboratory co-operation mean that genome-wide analyses can now be used to identify genetic variants that are robustly associated with the risk of developing psychiatric and neurological disorders. In contrast to the candidate gene approach, such screens may identify variants within genes which have a hitherto unappreciated role in disorder pathogenesis, and whose brain function is obscure. In this Perspective, I discuss how the behavioral functions of such genes may be investigated using model systems, drawing attention to the potential caveats and limitations with such approaches. The power of focused cross-species studies needs to be effectively exploited to enable useful insights into the molecular pathogenesis of common and disabling disorders, and ultimately to provide better clinical outcomes for patients. PMID- 22303384 TI - Whole genome sequences of a male and female supercentenarian, ages greater than 114 years. AB - Supercentenarians (age 110+ years old) generally delay or escape age-related diseases and disability well beyond the age of 100 and this exceptional survival is likely to be influenced by a genetic predisposition that includes both common and rare genetic variants. In this report, we describe the complete genomic sequences of male and female supercentenarians, both age >114 years old. We show that: (1) the sequence variant spectrum of these two individuals' DNA sequences is largely comparable to existing non-supercentenarian genomes; (2) the two individuals do not appear to carry most of the well-established human longevity enabling variants already reported in the literature; (3) they have a comparable number of known disease-associated variants relative to most human genomes sequenced to-date; (4) approximately 1% of the variants these individuals possess are novel and may point to new genes involved in exceptional longevity; and (5) both individuals are enriched for coding variants near longevity-associated variants that we discovered through a large genome-wide association study. These analyses suggest that there are both common and rare longevity-associated variants that may counter the effects of disease-predisposing variants and extend lifespan. The continued analysis of the genomes of these and other rare individuals who have survived to extremely old ages should provide insight into the processes that contribute to the maintenance of health during extreme aging. PMID- 22303386 TI - Trans-splicing in Higher Eukaryotes: Implications for Cancer Development? AB - Trans-splicing, the possibility of exons from distinct pre-mRNAs to join together, is still a concept in gene expression that is generally regarded of limited significance. However, recent work has provided evidence that in human tumors trans-splicing events may precede chromosomal rearrangements. In fact, it has been suggested that the trans-spliced molecules could act as "guides" that facilitate the genomic translocation. This perspective highlights the development of the ideas of trans-splicing in higher eukaryotes during the last 25 years, from a bizarre phenomenon to a biological event that is attaining stronger recognition. PMID- 22303385 TI - Epigenetic Contributions to the Relationship between Cancer and Dietary Intake of Nutrients, Bioactive Food Components, and Environmental Toxicants. AB - Epigenetics is the study of heritable changes in gene expression that occur without a change in DNA sequence. Cancer is a multistep process derived from combinational crosstalk between genetic alterations and epigenetic influences through various environmental factors. The observation that epigenetic changes are reversible makes them an attractive target for cancer prevention. Until recently, there have been difficulties studying epigenetic mechanisms in interactions between dietary factors and environmental toxicants. The development of the field of cancer epigenetics during the past decade has been advanced rapidly by genome-wide technologies - which initially employed microarrays but increasingly are using high-throughput sequencing - which helped to improve the quality of the analysis, increase the capacity of sample throughput, and reduce the cost of assays. It is particularly true for applications of cancer epigenetics in epidemiologic studies that examine the relationship among diet, epigenetics, and cancer because of the issues of tissue heterogeneity, the often limiting amount of DNA samples, and the significant cost of the analyses. This review offers an overview of the state of the science in nutrition, environmental toxicants, epigenetics, and cancer to stimulate further exploration of this important and developing area of science. Additional epidemiologic research is needed to clarify the relationship between these complex epigenetic mechanisms and cancer. PMID- 22303387 TI - Thousands of Novel Transcripts Identified in Mouse Cerebrum, Testis, and ES Cells Based on ribo-minus RNA Sequencing. AB - The high-throughput next-generation sequencing technologies provide an excellent opportunity for the detection of less-abundance transcripts that may not be identifiable by previously available techniques. Here, we report a discovery of thousands of novel transcripts (mostly non-coding RNAs) that are expressed in mouse cerebrum, testis, and embryonic stem (ES) cells, through an in-depth analysis of rmRNA-seq data. These transcripts show significant associations with transcriptional start and elongation signals. At the upstream of these transcripts we observed significant enrichment of histone marks (histone H3 lysine 4 trimethylation, H3K4me3), RNAPII binding sites, and cap analysis of gene expression tags that mark transcriptional start sites. Along the length of these transcripts, we also observed enrichment of histone H3 lysine 36 trimethylation (H3K36me3). Moreover, these transcripts show strong purifying selection in their genomic loci, exonic sequences, and promoter regions, implying functional constraints on the evolution of these transcripts. These results define a collection of novel transcripts in the mouse genome and indicate their potential functions in the mouse tissues and cells. PMID- 22303388 TI - The Beginning of the Road for Non-Coding RNAs in Normal Hematopoiesis and Hematologic Malignancies. AB - The field of non-coding RNAs (ncRNAs) encompasses a wide array of RNA classes that are indispensible for the regulation of cellular activities. However, de regulation of these ncRNAs can also play key roles in malignant transformation and cancer cell behavior. In this article we survey a select group of microRNAs and long ncRNAs that appear to contribute in keys ways to the development of acute and chronic leukemias, as well as contribute to their diagnosis, prognosis, and potentially, their treatment. PMID- 22303389 TI - A Network of Regulations by Small Non-Coding RNAs: The P-TEFb Kinase in Development and Pathology. AB - Part of the heterodimeric P-TEF-b element of the Pol II transcription machinery, the cyclin-dependent kinase 9 plays a critical role in gene expression. Phosphorylation of several residues in the polymerase is required for elongation of transcript. It determines the rates of transcription and thus, plays a critical role in several differentiation pathways, best documented in heart development. The synthesis and activity of the protein are tightly regulated in a coordinated manner by at least three non-coding RNAs. First, its kinase activity is reversibly inhibited by formation of a complex with the 334 nt 7SK RNA, from which it is released under conditions of stress. Then, heart development requires a maximal rate of synthesis during cardiomyocyte differentiation, followed by a decrease in the differentiated state. The latter is insured by microRNA-mediated translational inhibition. In a third mode of RNA control, increased levels of transcription are induced by small non-coding RNA molecules with sequences homologous to the transcript. Designated paramutation, this epigenetic variation, stable during development, and hereditarily transmitted in a non-Mendelian manner over several generations, is thought to be a response to the inactivation of one of the two alleles by an abnormal recombination event such as insertion of a transposon. PMID- 22303390 TI - Characterizing ncRNAs in Human Pathogenic Protists Using High-Throughput Sequencing Technology. AB - ncRNAs are key genes in many human diseases including cancer and viral infection, as well as providing critical functions in pathogenic organisms such as fungi, bacteria, viruses, and protists. Until now the identification and characterization of ncRNAs associated with disease has been slow or inaccurate requiring many years of testing to understand complicated RNA and protein gene relationships. High-throughput sequencing now offers the opportunity to characterize miRNAs, siRNAs, small nucleolar RNAs (snoRNAs), and long ncRNAs on a genomic scale, making it faster and easier to clarify how these ncRNAs contribute to the disease state. However, this technology is still relatively new, and ncRNA discovery is not an application of high priority for streamlined bioinformatics. Here we summarize background concepts and practical approaches for ncRNA analysis using high-throughput sequencing, and how it relates to understanding human disease. As a case study, we focus on the parasitic protists Giardia lamblia and Trichomonas vaginalis, where large evolutionary distance has meant difficulties in comparing ncRNAs with those from model eukaryotes. A combination of biological, computational, and sequencing approaches has enabled easier classification of ncRNA classes such as snoRNAs, but has also aided the identification of novel classes. It is hoped that a higher level of understanding of ncRNA expression and interaction may aid in the development of less harsh treatment for protist-based diseases. PMID- 22303391 TI - Unraveling the Mystery of Cancer by Secretory microRNA: Horizontal microRNA Transfer between Living Cells. AB - microRNAs (miRNAs) have been identified as a fine-tuner in a wide array of biological processes, including development, organogenesis, metabolism, and homeostasis. Deregulation of miRNAs causes diseases, especially cancer. This occurs through a variety of mechanisms, such as genetic alterations, epigenetic regulation, or altered expression of transcription factors, which target miRNAs. Recently, it was discovered that extracellular miRNAs circulate in the blood of both healthy and diseased patients. Since RNase is abundant in the bloodstream, most of the secretory miRNAs are contained in apoptotic bodies, microvesicles, and exosomes or bound to the RNA-binding proteins. However, the secretory mechanism and biological function, as well as the significance of extracellular miRNAs, remain largely unclear. In this article, we summarize the latest and most significant discoveries in recent peer-reviewed research on secretory miRNA involvement in many aspects of physiological and pathological conditions, with a special focus on cancer. In addition, we discuss a new aspect of cancer research that is revealed by the emergence of "secretory miRNA." PMID- 22303392 TI - Interpreting gene-expression profiles in transplantation: a critical appraisal. AB - Oligonucleotide microarray technology has created a small revolution in the transplant community because it has helped to decipher previously unknown molecular processes involved in allograft pathology, redefined molecular patterns of diseases that are indistinguishable at the pathological level and made possible the definition of new prognostic factors for long-term graft outcomes. However, given the tremendous complexity of the biological processes that are involved in the pathology of a transplanted organ, the interpretation of transcriptomic data can be speculative and oversimplified. Here, we discuss critical considerations regarding the nature of the object studied by cDNA microarray technology, the means by which it is observed, the interpretation of the observations, and whether the observations make sense in the context of transplant-related scientific questions. Given these limitations, we believe that global approaches based on more functional biological intermediates are necessary for a better understanding of the molecular processes that regulate the physiopathology of the transplanted organ. PMID- 22303393 TI - QTL Analysis of Type I and Type IIA Fibers in Soleus Muscle in a Cross between LG/J and SM/J Mouse Strains. AB - Properties of muscle fibers, i.e., their type, number and size, are important determinants of functional characteristics of skeletal muscle, and of the quality of meat in livestock. Genetic factors play an important role in determining variation in fiber properties, however, specific genes remain largely elusive. We examined histological properties of soleus muscle fibers in two strains of mice exhibiting a twofold difference in muscle mass, LG/J and SM/J, and their F2 intercross. The total number of muscle fibers (555 +/- 106; mean +/- SD) did not differ between the strains or between males and females. A higher percentage of type I fibers was observed in the LG/J compared to the SM/J strain (P < 0.001) in both males (45 +/- 3 vs. 37 +/- 4%) and females (58 +/- 4 vs. 41 +/- 3%). Across strains, females had a higher percentage of type I fibers than males (P < 0.001), and the sex effect was greater in the LG/J strain (strain-by-sex interaction, P < 0.001). The cross-sectional area (CSA) did not differ between type I and type IIA fibers, but was greater in the LG/J than the SM/J strain (1365 +/- 268 vs. 825 +/ 229 MUm(2), P < 0.001). Three significant quantitative trait locus (QTL) affecting CSA for type I and type IIA fibers mapped to chromosomes (Chr) 1, 6, and 11 and three suggestive QTL for percentage of type I fibers mapped to Chr 2, 3, and 4. Within each significant QTL, regions of conserved synteny were also implicated in variation of similar traits in an analogous study in pigs. Our results provide the evidence that the intercross between the SM/J and LG/J strains is a promising model to search for genes affecting muscle fiber properties. PMID- 22303394 TI - RAS Mutations and Oncogenesis: Not all RAS Mutations are Created Equally. AB - Mutation in RAS proteins is one of the most common genetic alterations observed in human and experimentally induced rodent cancers. In vivo, oncogenic mutations have been shown to occur at exons 12, 13, and 61, resulting in any 1 of 19 possible point mutations in a given tumor for a specific RAS isoform. While some studies have suggested a possible role of different mutant alleles in determining tumor severity and phenotype, no general consensus has emerged on the oncogenicity of different mutant alleles in tumor formation and progression. Part of this may be due to a lack of a single, signature pathway that shows significant alterations between different mutations. Rather, it is likely that subtle differences in the activation, or lack thereof, of downstream effectors by different RAS mutant alleles may determine the eventual outcome in terms of tumor phenotype. This paper reviews our current understanding of the potential role of different RAS mutations on tumorigenesis, highlights studies in model cell culture and in vivo systems, and discusses the potential of expression array and computational network modeling to dissect out differences in activated RAS genes in conferring a transforming phenotype. PMID- 22303395 TI - Survey of SSC12 Regions Affecting Fatty Acid Composition of Intramuscular Fat Using High-Density SNP Data. AB - Fatty acid composition is a critical aspect of pork because it affects sensorial and technological aspects of meat quality and it is relevant for human health. Previous studies identified significant QTLs in porcine chromosome 12 for fatty acid profile of back fat (BF) and intramuscular fat (IMF). In the present study, 374 SNPs mapped in SSC12 from the 60K Porcine SNP Beadchip were used. We have combined linkage and association analyses with expression data analysis in order to identify regions of SSC12 that could affect fatty acid composition of IMF in longissimus muscle. The QTL scan showed a region around the 60-cM position that significantly affects palmitic fatty acid and two related fatty acid indexes. The Iberian QTL allele increased the palmitic content (+2.6% of mean trait). This QTL does not match any of those reported in the previous study on fatty acid composition of BF, suggesting different genetic control acting at both tissues. The SNP association analyses showed significant associations with linolenic and palmitic acids besides several indexes. Among the polymorphisms that affect palmitic fatty acid and match the QTL region at 60 cM, there were three that mapped in the Phosphatidylcholine transfer protein (PCTP) gene and one in the Acetyl-CoA Carboxylase ? gene (ACACA). Interestingly one of the PCTP SNPs also affected significantly unsaturated and double bound indexes and the ratio between polyunsaturated/monounsaturated fatty acids. Differential expression was assessed on longissimus muscle conditional on the genotype of the QTL and on the most significant SNPs, according to the results obtained in the former analyses. Results from the microarray expression analyses, validated by RT-qPCR, showed that PCTP expression levels significantly vary depending on the QTL as well as on the own PCTP genotype. The results obtained with the different approaches point out the PCTP gene as a powerful candidate underlying the QTL for palmitic content. PMID- 22303396 TI - Loss of mitochondrial membrane potential triggers the retrograde response extending yeast replicative lifespan. AB - In the budding yeast Saccharomyces cerevisiae, loss of mitochondrial DNA (rho(0)) can induce the retrograde response under appropriate conditions, resulting in increased replicative lifespan (RLS). Although the retrograde pathway has been extensively elaborated, the nature of the mitochondrial signal triggering this response has not been clear. Mitochondrial membrane potential (MMP) was severely reduced in rho(0) compared to rho(+) cells, and RLS was concomitantly extended. To examine the role of MMP in the retrograde response, MMP was increased in the rho(0) strain by introducing a mutation in the ATP1 gene, and it was decreased in rho(+) cells by deletion of COX4. The ATP1-111 mutation in rho(0) cells partially restored the MMP and reduced mean RLS to that of rho(+) cells. COX4 deletion decreased MMP in rho(+) cells to a value intermediate between rho(+) and rho(0) cells and similarly increased RLS. The increase in expression of CIT2, the diagnostic gene for the retrograde response, seen in rho(0) cells, was substantially suppressed in the presence of the ATP1-111 mutation. In contrast, CIT2 expression increased in rho(+) cells on deletion of COX4. Activation of the retrograde response results in the translocation of the transcription factor Rtg3 from the cytoplasm to the nucleus. Rtg3-GFP translocation to the nucleus was directly observed in rho(0) and rho(+)cox4Delta cells, but it was blunted in rho(0) cells with the ATP1-111 mutation. We conclude that a decrease in MMP is the signal that initiates the retrograde response and leads to increased RLS. PMID- 22303397 TI - Accurate microRNA Target Prediction Using Detailed Binding Site Accessibility and Machine Learning on Proteomics Data. AB - MicroRNAs (miRNAs) are a class of small regulatory genes regulating gene expression by targeting messenger RNA. Though computational methods for miRNA target prediction are the prevailing means to analyze their function, they still miss a large fraction of the targeted genes and additionally predict a large number of false positives. Here we introduce a novel algorithm called DIANA microT-ANN which combines multiple novel target site features through an artificial neural network (ANN) and is trained using recently published high throughput data measuring the change of protein levels after miRNA overexpression, providing positive and negative targeting examples. The features characterizing each miRNA recognition element include binding structure, conservation level, and a specific profile of structural accessibility. The ANN is trained to integrate the features of each recognition element along the 3'untranslated region into a targeting score, reproducing the relative repression fold change of the protein. Tested on two different sets the algorithm outperforms other widely used algorithms and also predicts a significant number of unique and reliable targets not predicted by the other methods. For 542 human miRNAs DIANA-microT-ANN predicts 120000 targets not provided by TargetScan 5.0. The algorithm is freely available at http://microrna.gr/microT-ANN. PMID- 22303398 TI - MicroRNAs - Important Molecules in Lung Cancer Research. AB - MicroRNAs (miRNA) are important regulators of gene expression. They are involved in many physiological processes ensuring the cellular homeostasis of human cells. Alterations of the miRNA expression have increasingly been associated with pathophysiologic changes of cancer cells making miRNAs currently to one of the most analyzed molecules in cancer research. Here, we provide an overview of miRNAs in lung cancer. Specifically, we address biological functions of miRNAs in lung cancer cells, miRNA signatures generated from tumor tissue and from patients' body fluids, the potential of miRNAs as diagnostic and prognostic biomarker for lung cancer, and its role as therapeutic target. PMID- 22303399 TI - When one and one gives more than two: challenges and opportunities of integrative omics. AB - Since the dawn of the post-genomic era a myriad of novel high-throughput technologies have been developed that are capable of measuring thousands of biological molecules at once, giving rise to various "omics" platforms. These advances offer the unique opportunity to study how individual parts of a biological system work together to produce emerging phenotypes. Today, many research laboratories are moving toward applying multiple omics platforms to analyze the same biological samples. In addition, network information of interacting molecules is being incorporated more and more into the analysis and interpretation of these multiple omics datasets, which provides novel ways to integrate multiple layers of heterogeneous biological information into a single coherent picture. Here, we provide a perspective on how such recent "integrative omics" efforts are likely going to shift biological paradigms once again, and what challenges lie ahead. PMID- 22303400 TI - Epigenetics: a new challenge in the post-genomic era of livestock. PMID- 22303401 TI - The Long Non-Coding RNAs: A New (P)layer in the "Dark Matter". AB - The transcriptome of a cell is represented by a myriad of different RNA molecules with and without protein-coding capacities. In recent years, advances in sequencing technologies have allowed researchers to more fully appreciate the complexity of whole transcriptomes, showing that the vast majority of the genome is transcribed, producing a diverse population of non-protein coding RNAs (ncRNAs). Thus, the biological significance of non-coding RNAs (ncRNAs) have been largely underestimated. Amongst these multiple classes of ncRNAs, the long non coding RNAs (lncRNAs) are apparently the most numerous and functionally diverse. A small but growing number of lncRNAs have been experimentally studied, and a view is emerging that these are key regulators of epigenetic gene regulation in mammalian cells. LncRNAs have already been implicated in human diseases such as cancer and neurodegeneration, highlighting the importance of this emergent field. In this article, we review the catalogs of annotated lncRNAs and the latest advances in our understanding of lncRNAs. PMID- 22303402 TI - A Simple PCR-RFLP Method for Genetic Phase Determination in Compound Heterozygotes. AB - When susceptibility to diseases is caused by cis-effects of multiple alleles at adjacent polymorphic sites, it may be difficult to assess with confidence the genetic phase and identify individuals carrying the risk haplotype. Experimental assessment of genetic phase is still challenging and most population studies use statistical approaches to infer haplotypes given the observed genotypes. While these statistical approaches are powerful and have been proven very useful in large scale genetic population studies, they may be prone to errors in studies with small sample size, especially in the presence of compound heterozygotes. Here, we describe a simple and novel approach using the popular PCR-RFLP based strategy to assess the genetic phase in compound heterozygotes. We apply this method to two extensively studied SNPs in two clustered immune-related genes: The -308 (G > A) and the +252 (A > G) SNPs of the tumor necrosis factor (TNF) alpha and the lymphotoxin alpha (LTA) genes, respectively. Using this method, we successfully determined the genetic phase of these two SNPs in known compound heterozygous individuals and in every sample tested. We show that the A allele of TNF -308 is carried on the same chromosome as the LTA +252(G) allele. PMID- 22303403 TI - Six Degrees of Epistasis: Statistical Network Models for GWAS. AB - There is growing evidence that much more of the genome than previously thought is required to explain the heritability of complex phenotypes. Recent studies have demonstrated that numerous common variants from across the genome explain portions of genetic variability, spawning various avenues of research directed at explaining the remaining heritability. This polygenic structure is also the motivation for the growing application of pathway and gene set enrichment techniques, which have yielded promising results. These findings suggest that the coordination of genes in pathways that are known to occur at the gene regulatory level also can be detected at the population level. Although genes in these networks interact in complex ways, most population studies have focused on the additive contribution of common variants and the potential of rare variants to explain additional variation. In this brief review, we discuss the potential to explain additional genetic variation through the agglomeration of multiple gene gene interactions as well as main effects of common variants in terms of a network paradigm. Just as is the case for single-locus contributions, we expect each gene-gene interaction edge in the network to have a small effect, but these effects may be reinforced through hubs and other connectivity structures in the network. We discuss some of the opportunities and challenges of network methods for analyzing genome-wide association studies (GWAS) such as the study of hubs and motifs, and integrating other types of variation and environmental interactions. Such network approaches may unveil hidden variation in GWAS, improve understanding of mechanisms of disease, and possibly fit into a network paradigm of evolutionary genetics. PMID- 22303404 TI - On the Aggregation of Multimarker Information for Marker-Set and Sequencing Data Analysis: Genotype Collapsing vs. Similarity Collapsing. AB - Methods that collapse information across genetic markers when searching for association signals are gaining momentum in the literature. Although originally developed to achieve a better balance between retaining information and controlling degrees of freedom when performing multimarker association analysis, these methods have recently been proven to be a powerful tool for identifying rare variants that contribute to complex phenotypes. The information among markers can be collapsed at the genotype level, which focuses on the mean of genetic information, or the similarity level, which focuses on the variance of genetic information. The aim of this work is to understand the strengths and weaknesses of these two collapsing strategies. Our results show that neither collapsing strategy outperforms the other across all simulated scenarios. Two factors that dominate the performance of these strategies are the signal-to-noise ratio and the underlying genetic architecture of the causal variants. Genotype collapsing is more sensitive to the marker set being contaminated by noise loci than similarity collapsing. In addition, genotype collapsing performs best when the genetic architecture of the causal variants is not complex (e.g., causal loci with similar effects and similar frequencies). Similarity collapsing is more robust as the complexity of the genetic architecture increases and outperforms genotype collapsing when the genetic architecture of the marker set becomes more sophisticated (e.g., causal loci with various effect sizes or frequencies and potential non-linear or interactive effects). Because the underlying genetic architecture is not known a priori, we also considered a two-stage analysis that combines the two top-performing methods from different collapsing strategies. We find that it is reasonably robust across all simulated scenarios. PMID- 22303405 TI - Toward an epigenetic view of our musical mind. AB - We are transient beings, in a world of constantly changing culture. At home in the fields of Art and Science, seemingly capable of magnificent abstractions, humans have an intense need to externalize their insights. Music is an art and a highly transmissible cultural product, but we still have an incomplete understanding of how our musical experience shapes and is vividly retained within our brain, and how it affects our behavior. However, the developing field of social epigenetics is now helping us to describe how communication and emotion, prime hallmarks of music, can be linked to a transmissible, biochemical change. PMID- 22303406 TI - Box-Cox Transformation and Random Regression Models for Fecal egg Count Data. AB - Accurate genetic evaluation of livestock is based on appropriate modeling of phenotypic measurements. In ruminants, fecal egg count (FEC) is commonly used to measure resistance to nematodes. FEC values are not normally distributed and logarithmic transformations have been used in an effort to achieve normality before analysis. However, the transformed data are often still not normally distributed, especially when data are extremely skewed. A series of repeated FEC measurements may provide information about the population dynamics of a group or individual. A total of 6375 FEC measures were obtained for 410 animals between 1992 and 2003 from the Beltsville Agricultural Research Center Angus herd. Original data were transformed using an extension of the Box-Cox transformation to approach normality and to estimate (co)variance components. We also proposed using random regression models (RRM) for genetic and non-genetic studies of FEC. Phenotypes were analyzed using RRM and restricted maximum likelihood. Within the different orders of Legendre polynomials used, those with more parameters (order 4) adjusted FEC data best. Results indicated that the transformation of FEC data utilizing the Box-Cox transformation family was effective in reducing the skewness and kurtosis, and dramatically increased estimates of heritability, and measurements of FEC obtained in the period between 12 and 26 weeks in a 26-week experimental challenge period are genetically correlated. PMID- 22303407 TI - Genome-Wide Identification and Quantification of cis- and trans-Regulated Genes Responding to Marek's Disease Virus Infection via Analysis of Allele-Specific Expression. AB - Marek's disease (MD) is a commercially important neoplastic disease of chickens caused by Marek's disease virus (MDV), a naturally occurring oncogenic alphaherpesvirus. Selecting for increased genetic resistance to MD is a control strategy that can augment vaccinal control measures. To identify high-confidence candidate MD resistance genes, we conducted a genome-wide screen for allele specific expression (ASE) amongst F(1) progeny of two inbred chicken lines that differ substantially in MD resistance. High throughput sequencing was initially used to profile transcriptomes from pools of uninfected and infected individuals at 4 days post-infection to identify any genes showing ASE in response to MDV infection. RNA sequencing identified 22,655 single nucleotide polymorphisms (SNPs) of which 5,360 in 3,773 genes exhibited significant allelic imbalance. Illumina GoldenGate assays were subsequently used to quantify regulatory variation controlled at the gene (cis) and elsewhere in the genome (trans) by examining differences in expression between F(1) individuals and artificial F(1) RNA pools over six time periods in 1,536 of the most significant SNPs identified by RNA sequencing. Allelic imbalance as a result of cis-regulatory changes was confirmed in 861 of the 1,233 GoldenGate assays successfully examined. Furthermore we have identified seven genes that display trans-regulation only in infected animals and ~500 SNP that show a complex interaction between cis- and trans-regulatory changes. Our results indicate ASE analyses are a powerful approach to identify regulatory variation responsible for differences in transcript abundance in genes underlying complex traits. And the genes with SNPs exhibiting ASE provide a strong foundation to further investigate the causative polymorphisms and genetic mechanisms for MD resistance. Finally, the methods used here for identifying specific genes and SNPs have practical implications for applying marker-assisted selection to complex traits that are difficult to measure in agricultural species, when expression differences are expected to control a portion of the phenotypic variance. PMID- 22303408 TI - Moving toward System Genetics through Multiple Trait Analysis in Genome-Wide Association Studies. AB - Association studies are a staple of genotype-phenotype mapping studies, whether they are based on single markers, haplotypes, candidate genes, genome-wide genotypes, or whole genome sequences. Although genetic epidemiological studies typically contain data collected on multiple traits which themselves are often correlated, most analyses have been performed on single traits. Here, I review several methods that have been developed to perform multiple trait analysis. These methods range from traditional multivariate models for systems of equations to recently developed graphical approaches based on network theory. The application of network theory to genetics is termed systems genetics and has the potential to address long-standing questions in genetics about complex processes such as coordinate regulation, homeostasis, and pleiotropy. PMID- 22303409 TI - Modeling haplotype-haplotype interactions in case-control genetic association studies. AB - Haplotype analysis has been increasingly used to study the genetic basis of human diseases, but models for characterizing genetic interactions between haplotypes from different chromosomal regions have not been well developed in the current literature. In this article, we describe a statistical model for testing haplotype-haplotype interactions for human diseases with a case-control genetic association design. The model is formulated on a contingency table in which cases and controls are typed for the same set of molecular markers. By integrating well established quantitative genetic principles, the model is equipped with a capacity to characterize physiologically meaningful epistasis arising from interactions between haplotypes from different chromosomal regions. The model allows the partition of epistasis into different components due to additive * additive, additive * dominance, dominance * additive, and dominance * dominance interactions. We derive the EM algorithm to estimate and test the effects of each of these components on differences in the pattern of genetic variation between cases and controls and, therefore, examine their role in the pathogenesis of human diseases. The method was further extended to investigate gene-environment interactions expressed at the haplotype level. The statistical properties of the models were investigated through simulation studies and its usefulness and utilization validated by analyzing the genetic association of sarcoidosis from a human genetics project. PMID- 22303410 TI - Regular exercise, subjective wellbeing, and internalizing problems in adolescence: causality or genetic pleiotropy? AB - This study tests in a genetically informative design whether exercise behavior causally influences subjective wellbeing (SWB) and internalizing problems (INT). If exercise causally influences SWB and INT, genetic and environmental factors influencing exercise behavior will also influence SWB and INT. Furthermore, within genetically identical (MZ) twin pairs, the twin who exercises more should also show higher levels of SWB and lower levels of INT, than the co-twin who exercises less, because genetic confounding is excluded. Data on these phenotypes were available in a sample of 6317 adolescent twins and 1180 non-twin-siblings. Most participants had longitudinal data with 2-year follow-up. Exercise behavior was cross-sectionally and longitudinally associated with fewer internalizing problems and increased SWB (correlations ranged from 0.12 to 0.16). Cross sectional and longitudinal associations were mainly accounted for by genetic factors, whereas the contribution of environmental factors was negligible. Within MZ twin pairs, the twin who exercised more did not show fewer internalizing problems and increased SWB. This was found cross-sectionally and longitudinally. We conclude that exercise behavior is associated with fewer internalizing problems and higher levels of SWB. The association largely reflects the effects of common genetic factors on these traits. PMID- 22303411 TI - PAX Genes in Cancer; Friends or Foes? AB - PAX genes have been shown to be critically required for the development of specific tissues and organs during embryogenesis. In addition, PAX genes are expressed in a handful of adult tissues where they are thought to play important roles, usually different from those in embryogenesis. A common theme in adult tissues is a requirement for PAX gene expression in adult stem cell maintenance or tissue regeneration. The connections between adult stem cell PAX gene expression and cancer are intriguing, and the literature is replete with examples of PAX gene expression in either situation. Here we systematically review the literature and present an overview of postnatal PAX gene expression in normal and cancerous tissue. We discuss the potential link between PAX gene expression in adult tissue and cancer. In addition, we discuss whether persistent PAX gene expression in cancer is favorable or unfavorable. PMID- 22303412 TI - Induction of phase 2 antioxidant enzymes by broccoli sulforaphane: perspectives in maintaining the antioxidant activity of vitamins a, C, and e. AB - Consumption of fruits and vegetables is recognized as an important part of a healthy diet. Increased consumption of cruciferous vegetables in particular has been associated with a decreased risk of several degenerative and chronic diseases, including cardiovascular disease and certain cancers. Members of the cruciferous vegetable family, which includes broccoli, Brussels sprouts, cauliflower, and cabbage, accumulate significant concentrations of glucosinolates, which are metabolized in vivo to biologically active isothiocyanates (ITCs). The ITC sulforaphane, which is derived from glucoraphanin, has garnered particular interest as an indirect antioxidant due to its extraordinary ability to induce expression of several enzymes via the KEAP1/Nrf2/ARE pathway. Nrf2/ARE gene products are typically characterized as Phase II detoxification enzymes and/or antioxidant (AO) enzymes. Over the last decade, human clinical studies have begun to provide in vivo evidence of both Phase II and AO enzyme induction by SF. Many AO enzymes are redox cycling enzymes that maintain redox homeostasis and activity of free radical scavengers such as vitamins A, C, and E. In this review, we present the existing evidence for induction of PII and AO enzymes by SF, the interactions of SF-induced AO enzymes and proposed maintenance of the essential vitamins A, C, and E, and, finally, the current view of genotypic effects on ITC metabolism and AO enzyme induction and function. PMID- 22303413 TI - The etiology of observed negative emotionality from 14 to 24 months. AB - We examined the magnitude of genetic and environmental influences on observed negative emotionality at age 14, 20, and 24 months. Participants were 403 same sex twin pairs recruited from the Longitudinal Twin Study whose emotional responses to four different situations were coded by independent raters. Negative emotionality showed significant consistency across settings, and there was evidence of a latent underlying negative emotionality construct. Heritability decreased, and the magnitude of shared environmental influences increased, for the latent negative emotionality construct from age 14 to 24 months. There were significant correlations between negative emotionality assessed at age 14, 20, and 24 months, and results suggested common genetic and shared environmental influences affecting negative emotionality across age, and that age-specific influences are limited to non-shared environmental influences, which include measurement error. PMID- 22303414 TI - Promoter de-methylation of cyclin D2 by sulforaphane in prostate cancer cells. AB - Sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables, induces potent anti-proliferative effects in prostate cancer cells. One mechanism that may contribute to the anti-proliferative effects of SFN is the modulation of epigenetic marks, such as inhibition of histone deacetylase (HDAC) enzymes. However, the effects of SFN on other common epigenetic marks such as DNA methylation are understudied. Promoter hyper-methylation of cyclin D2, a major regulator of cell cycle, is correlated with prostate cancer progression, and restoration of cyclin D2 expression exerts anti-proliferative effects on LnCap prostate cancer cells. Our study aimed to investigate the effects of SFN on DNA methylation status of cyclin D2 promoter, and how alteration in promoter methylation impacts cyclin D2 gene expression in LnCap cells. We found that SFN significantly decreased the expression of DNA methyltransferases (DNMTs), especially DNMT1 and DNMT3b. Furthermore, SFN significantly decreased methylation in cyclin D2 promoter regions containing c-Myc and multiple Sp1 binding sites. Reduced methlyation of cyclin D2 promoter corresponded to an increase in cyclin D2 transcript levels, suggesting that SFN may de-repress methylation-silenced cyclin D2 by impacting epigenetic pathways. Our results demonstrated the ability of SFN to epigenetically modulate cyclin D2 expression, and provide novel insights into the mechanisms by which SFN may regulate gene expression as a prostate cancer chemopreventive agent. PMID- 22303415 TI - Potentials of mouthwashes in disinfecting cariogenic bacteria and biofilms leading to inhibition of caries. AB - OBJECTIVES: The aim of this study was to compare the effects of certain commercially available mouthwashes on cariogenic bacteria and biofilms, following the acquisition of inhibition potentials of caries. MATERIALS AND METHODS: Mouthwashes containing I) chlorhexidine gluconate (CHG; 0.0005% w/v), II) benzethonium chloride (BTC; 0.01% w/v), III) an essential oil (Listerine), and IV) povidone-iodine (PVP-I; 0.035% w/v) were tested on planktonic cariogenic bacteria, biofilms, and an ex vivo caries model. Bacterial aliquots were inoculated with each solution separately and vortexed for 10 seconds at room temperature. Bacterial viability was subsequently investigated by fluorescence microscopy (FM) after staining with a BacLight viability kit and the number of colony-forming units (CFUs) was counted. Similarly, mouthwash solutions were applied to artificial cariogenic biofilms, and bacterial viability of the biofilms was investigated as stated above. Inhibition potentials of two selected mouthwashes of carious lesions were investigated using biofilm-induced caries and a secondary caries model. In all steps, a phosphate-buffered saline (PBS) solution was included as a control. RESULTS: Planktonic cariogenic bacteria and bacteria embedded in biofilms were killed in remarkably large numbers with Listerine and PVP-I treatment compared to PBS and other gargles. CFU counts also showed significant reduction after treatment with Listerine and PVP-I compared to other solutions (P<0.05). Listerine also displayed significant (P<0.05) inhibition effects in preventing the progression of demineralization. CONCLUSION: Bactericidal potencies of the mouthwashes varied significantly, suggesting that mouthwashes like Listerine can be useful for the prevention of caries and secondary caries. PMID- 22303416 TI - Expanding the Grading of Recommendations Assessment, Development, and Evaluation (Ex-GRADE) for Evidence-Based Clinical Recommendations: Validation Study. AB - Clinicians use general practice guidelines as a source of support for their intervention, but how much confidence should they place on these recommendations? How much confidence should patients place on these recommendations? Various instruments are available to assess the quality of evidence of research, such as the revised Wong scale (R-Wong) which examines the quality of research design, methodology and data analysis, and the revision of the assessment of multiple systematic reviews (R-AMSTAR), which examines the quality of systematic reviews.The Grading of Recommendation Assessment, Development, and Evaluation (GRADE) Working Group developed an instrument called the GRADE system in order to grade the quality of the evidence in studies and to evaluate the strength of recommendation of the intervention that is proposed in the published article. The GRADE looks at four factors to determine the quality of the evidence: study design, study quality, consistency, and directness. After combining the four components and assessing the grade of the evidence, the strength of recommendation of the intervention is established. The GRADE, however, only makes a qualitative assessment of the evidence and does not generate quantifiable data.In this study, we have quantified both the grading of the quality of evidence and also the strength of recommendation of the original GRADE, hence expanding the GRADE. This expansion of the GRADE (Ex-GRADE) permits the creation of a new instrument that can produce tangible data and possibly bridge the gap between evidence-based research and evidence-based clinical practice. PMID- 22303434 TI - Ologs: a categorical framework for knowledge representation. AB - In this paper we introduce the olog, or ontology log, a category-theoretic model for knowledge representation (KR). Grounded in formal mathematics, ologs can be rigorously formulated and cross-compared in ways that other KR models (such as semantic networks) cannot. An olog is similar to a relational database schema; in fact an olog can serve as a data repository if desired. Unlike database schemas, which are generally difficult to create or modify, ologs are designed to be user friendly enough that authoring or reconfiguring an olog is a matter of course rather than a difficult chore. It is hoped that learning to author ologs is much simpler than learning a database definition language, despite their similarity. We describe ologs carefully and illustrate with many examples. As an application we show that any primitive recursive function can be described by an olog. We also show that ologs can be aligned or connected together into a larger network using functors. The various methods of information flow and institutions can then be used to integrate local and global world-views. We finish by providing several different avenues for future research. PMID- 22303435 TI - Boolean models of biosurfactants production in Pseudomonas fluorescens. AB - Cyclolipopeptides (CLPs) are biosurfactants produced by numerous Pseudomonas fluorescens strains. CLP production is known to be regulated at least by the GacA/GacS two-component pathway, but the full regulatory network is yet largely unknown. In the clinical strain MFN1032, CLP production is abolished by a mutation in the phospholipase C gene (plcC) and not restored by plcC complementation. Their production is also subject to phenotypic variation. We used a modelling approach with Boolean networks, which takes into account all these observations concerning CLP production without any assumption on the topology of the considered network. Intensive computation yielded numerous models that satisfy these properties. All models minimizing the number of components point to a bistability in CLP production, which requires the presence of a yet unknown key self-inducible regulator. Furthermore, all suggest that a set of yet unexplained phenotypic variants might also be due to this epigenetic switch. The simplest of these Boolean networks was used to propose a biological regulatory network for CLP production. This modelling approach has allowed a possible regulation to be unravelled and an unusual behaviour of CLP production in P. fluorescens to be explained. PMID- 22303436 TI - Homology inference of protein-protein interactions via conserved binding sites. AB - The coverage and reliability of protein-protein interactions determined by high throughput experiments still needs to be improved, especially for higher organisms, therefore the question persists, how interactions can be verified and predicted by computational approaches using available data on protein structural complexes. Recently we developed an approach called IBIS (Inferred Biomolecular Interaction Server) to predict and annotate protein-protein binding sites and interaction partners, which is based on the assumption that the structural location and sequence patterns of protein-protein binding sites are conserved between close homologs. In this study first we confirmed high accuracy of our method and found that its accuracy depends critically on the usage of all available data on structures of homologous complexes, compared to the approaches where only a non-redundant set of complexes is employed. Second we showed that there exists a trade-off between specificity and sensitivity if we employ in the prediction only evolutionarily conserved binding site clusters or clusters supported by only one observation (singletons). Finally we addressed the question of identifying the biologically relevant interactions using the homology inference approach and demonstrated that a large majority of crystal packing interactions can be correctly identified and filtered by our algorithm. At the same time, about half of biological interfaces that are not present in the protein crystallographic asymmetric unit can be reconstructed by IBIS from homologous complexes without the prior knowledge of crystal parameters of the query protein. PMID- 22303437 TI - Defining Plasmodium falciparum treatment in South West Asia: a randomized trial comparing artesunate or primaquine combined with chloroquine or SP. AB - INTRODUCTION: Antimalarial resistance has led to a global policy of artemisinin based combination therapy. Despite growing resistance chloroquine (CQ) remained until recently the official first-line treatment for falciparum malaria in Pakistan, with sulfadoxine-pyrimethamine (SP) second-line. Co-treatment with the gametocytocidal primaquine (PQ) is recommended for transmission control in South Asia. The relative effect of artesunate (AS) or primaquine, as partner drugs, on clinical outcomes and gametocyte carriage in this setting were unknown. METHODS: A single-blinded, randomized trial among Afghan refugees in Pakistan compared six treatment arms: CQ; CQ+(single-dose)PQ; CQ+(3 d)AS; SP; SP+(single-dose)PQ, and SP+(3 d)AS. The objectives were to compare treatment failure rates and effect on gametocyte carriage, of CQ or SP monotherapy against the respective combinations (PQ or AS). Outcomes included trophozoite and gametocyte clearance (read by light microscopy), and clinical and parasitological failure. FINDINGS: A total of 308 (87%) patients completed the trial. Failure rates by day 28 were: CQ 55/68 (81%); CQ+AS 19/67 (28%), SP 4/41 (9.8%), SP+AS 1/41 (2.4%). The addition of PQ to CQ or SP did not affect failure rates (CQ+PQ 49/67 (73%) failed; SP+PQ 5/33 (16%) failed). AS was superior to PQ at clearing gametocytes; gametocytes were seen on d7 in 85% of CQ, 40% of CQ+PQ, 21% of CQ+AS, 91% of SP, 76% of SP+PQ and 23% of SP+AS treated patients. PQ was more effective at clearing older gametocyte infections whereas AS was more effective at preventing emergence of mature gametocytes, except in cases that recrudesced. CONCLUSIONS: CQ is no longer appropriate by itself or in combination. These findings influenced the replacement of CQ with SP+AS for first-line treatment of uncomplicated falciparum malaria in the WHO Eastern Mediterranean Region. The threat of SP resistance remains as SP monotherapy is still common. Three day AS was superior to single dose PQ for reducing gametocyte carriage. TRIAL REGISTRATION: ClinicalTrials.gov NCT00959517. PMID- 22303438 TI - Primary xenografts of human prostate tissue as a model to study angiogenesis induced by reactive stroma. AB - Characterization of the mechanism(s) of androgen-driven human angiogenesis could have significant implications for modeling new forms of anti-angiogenic therapies for CaP and for developing targeted adjuvant therapies to improve efficacy of androgen-deprivation therapy. However, models of angiogenesis by human endothelial cells localized within an intact human prostate tissue architecture are until now extremely limited. This report characterizes the burst of angiogenesis by endogenous human blood vessels in primary xenografts of fresh surgical specimens of benign prostate or prostate cancer (CaP) tissue that occurs between Days 6-14 after transplantation into SCID mice pre-implanted with testosterone pellets. The wave of human angiogenesis was preceded by androgen mediated up-regulation of VEGF-A expression in the stromal compartment. The neo vessel network anastomosed to the host mouse vascular system between Days 6-10 post-transplantation, the angiogenic response ceased by Day 15, and by Day 30 the vasculature had matured and stabilized, as indicated by a lack of leakage of serum components into the interstitial tissue space and by association of nascent endothelial cells with mural cells/pericytes. The angiogenic wave was concurrent with the appearance of a reactive stroma phenotype, as determined by staining for alpha-SMA, Vimentin, Tenascin, Calponin, Desmin and Masson's trichrome, but the reactive stroma phenotype appeared to be largely independent of androgen availability. Transplantation-induced angiogenesis by endogenous human endothelial cells present in primary xenografts of benign and malignant human prostate tissue was preceded by induction of androgen-driven expression of VEGF by the prostate stroma, and was concurrent with and the appearance of a reactive stroma phenotype. Androgen-modulated expression of VEGF-A appeared to be a causal regulator of angiogenesis, and possibly of stromal activation, in human prostate xenografts. PMID- 22303439 TI - Metabolic profiles and cDNA-AFLP analysis of Salvia miltiorrhiza and Salvia castanea Diel f. tomentosa Stib. AB - Plants of the genus Salvia produce various types of phenolic compounds and tanshinones which are effective for treatment of coronary heart disease. Salvia miltiorrhiza and S. castanea Diels f. tomentosa Stib are two important members of the genus. In this study, metabolic profiles and cDNA-AFLP analysis of four samples were employed to identify novel genes potentially involved in phenolic compounds and tanshinones biosynthesis, including the red roots from the two species and two tanshinone-free roots from S. miltiorrhiza. The results showed that the red roots of S. castanea Diels f. tomentosa Stib produced high contents of rosmarinic acid (21.77 mg/g) and tanshinone IIA (12.60 mg/g), but low content of salvianolic acid B (1.45 mg/g). The red roots of S. miltiorrhiza produced high content of salvianolic acid B (18.69 mg/g), while tanshinones accumulation in this sample was much less than that in S. castanea Diels f. tomentosa Stib. Tanshinones were not detected in the two tanshinone-free samples, which produced high contents of phenolic compounds. A cDNA-AFLP analysis with 128 primer pairs revealed that 2300 transcript derived fragments (TDFs) were differentially expressed among the four samples. About 323 TDFs were sequenced, of which 78 TDFs were annotated with known functions through BLASTX searching the Genbank database and 14 annotated TDFs were assigned into secondary metabolic pathways through searching the KEGGPATHWAY database. The quantitative real-time PCR analysis indicated that the expression of 9 TDFs was positively correlated with accumulation of phenolic compounds and tanshinones. These TDFs additionally showed coordinated transcriptional response with 6 previously-identified genes involved in biosynthesis of tanshinones and phenolic compounds in S. miltiorrhiza hairy roots treated with yeast extract. The sequence data in the present work not only provided us candidate genes involved in phenolic compounds and tanshinones biosynthesis but also gave us further insight into secondary metabolism in Salvia. PMID- 22303440 TI - Safety issues of long-term glucose load in patients on peritoneal dialysis--a 7 year cohort study. AB - BACKGROUND: Effects of long-term glucose load on peritoneal dialysis (PD) patient safety and outcomes have seldom been reported. This study demonstrates the influence of long-term glucose load on patient and technique survival. METHODS: We surveyed 173 incident PD patients. Long-term glucose load was evaluated by calculating the average dialysate glucose concentration since initiation of PD. Risk factors were assessed by fitting Cox's models with repeatedly measured time dependent covariates. RESULTS: We noted that older age, higher glucose concentration, and lower residual renal function (RRF) were significantly associated with a worse patient survival. We found that female gender, absence of diabetes, lower glucose concentration, use of icodextrin, higher serum high density lipoprotein cholesterol, and higher RRF were significantly associated with a better technique survival. CONCLUSIONS: Long-term glucose load predicted mortality and technique failure in chronic PD patients. These findings emphasize the importance of minimizing glucose load in PD patients. PMID- 22303441 TI - A new eusuchian crocodyliform with novel cranial integument and its significance for the origin and evolution of Crocodylia. AB - Crocodyliforms were one of the most successful groups of Mesozoic tetrapods, radiating into terrestrial, semiaquatic and marine environments, while occupying numerous trophic niches, including carnivorous, insectivorous, herbivorous, and piscivorous species. Among these taxa were the enigmatic, poorly represented flat headed crocodyliforms from the late Cretaceous of northern Africa. Here we report a new, giant crocodyliform from the early Late Cretaceous (Cenomanian) Kem Kem Formation of Morocco. Represented by a partial braincase, the taxon has an extremely long, flat skull with large jaw and craniocervical muscles. The skull roof is ridged and ornamented with a broad, rough boss surrounded by significant vascular impressions, likely forming an integumentary structure unique among crocodyliforms. Size estimates using endocranial volume indicate the specimen was very large. The taxon possesses robust laterosphenoids with laterally oriented capitate processes and isolated epipterygoids, features allying it with derived eusuchians. Phylogenetic analysis finds the taxon to be a derived eusuchian and sister taxon to Aegyptosuchus, a poorly understood, early Late Cretaceous taxon from the Bahariya formation. This clade forms the sister clade of crown-group Crocodylia, making these taxa the earliest eusuchian crocodyliforms known from Africa. These results shift phylogenetic and biogeographical hypotheses on the origin of modern crocodylians towards the circum-Tethyean region and provide important new data on eusuchian morphology and evolution. PMID- 22303442 TI - Increased inter-colony fusion rates are associated with reduced COI haplotype diversity in an invasive colonial ascidian Didemnum vexillum. AB - Considerable progress in our understanding of the population genetic changes associated with biological invasions has been made over the past decade. Using selectively neutral loci, it has been established that reductions in genetic diversity, reflecting founder effects, have occurred during the establishment of some invasive populations. However, some colonial organisms may actually gain an ecological advantage from reduced genetic diversity because of the associated reduction in inter-colony conflict. Here we report population genetic analyses, along with colony fusion experiments, for a highly invasive colonial ascidian, Didemnum vexillum. Analyses based on mitochondrial cytochrome oxidase I (COI) partial coding sequences revealed two distinct D. vexillum clades. One COI clade appears to be restricted to the probable native region (i.e., north-west Pacific Ocean), while the other clade is present in widely dispersed temperate coastal waters around the world. This clade structure was supported by 18S ribosomal DNA (rDNA) sequence data, which revealed a one base-pair difference between the two clades. Recently established populations of D. vexillum in New Zealand displayed greatly reduced COI genetic diversity when compared with D. vexillum in Japan. In association with this reduction in genetic diversity was a significantly higher inter-colony fusion rate between randomly paired New Zealand D. vexillum colonies (80%, standard deviation +/-18%) when compared with colonies found in Japan (27%, standard deviation +/-15%). The results of this study add to growing evidence that for colonial organisms reductions in population level genetic diversity may alter colony interaction dynamics and enhance the invasive potential of newly colonizing species. PMID- 22303443 TI - CCL2 is associated with a faster rate of cognitive decline during early stages of Alzheimer's disease. AB - Chemokine (C-C motif) receptor 2 (CCR2)-signaling can mediate accumulation of microglia at sites affected by neuroinflammation. CCR2 and its main ligand CCL2 (MCP-1) might also be involved in the altered metabolism of beta-amyloid (Abeta) underlying Alzheimer's disease (AD). We therefore measured the levels of CCL2 and three other CCR2 ligands, i.e. CCL11 (eotaxin), CCL13 (MCP-4) and CCL26 (eotaxin 3), in the cerebrospinal fluid (CSF) and plasma of 30 controls and 119 patients with mild cognitive impairment (MCI) at baseline. During clinical follow-up 52 MCI patients were clinically stable for five years, 47 developed AD (i.e. cases with prodromal AD at baseline) and 20 developed other dementias. Only CSF CCL26 was statistically significantly elevated in patients with prodromal AD when compared to controls (p = 0.002). However, in patients with prodromal AD, the CCL2 levels in CSF at baseline correlated with a faster cognitive decline during follow-up (r(s) = 0.42, p = 0.004). Furthermore, prodromal AD patients in the highest tertile of CSF CCL2 exhibited a significantly faster cognitive decline (p<0.001) and developed AD dementia within a shorter time period (p<0.003) compared to those in the lowest tertile. Finally, in the entire MCI cohort, CSF CCL2 could be combined with CSF Tau, P-tau and Abeta42 to predict both future conversion to AD and the rate of cognitive decline. If these results are corroborated in future studies, CCL2 in CSF could be a candidate biomarker for prediction of future disease progression rate in prodromal AD. Moreover, CCR2 related signaling pathways might be new therapeutic targets for therapies aiming at slowing down the disease progression rate of AD. PMID- 22303445 TI - Inhibition of Wnt/beta-catenin signaling by a soluble collagen-derived frizzled domain interacting with Wnt3a and the receptors frizzled 1 and 8. AB - The Wnt/beta-catenin pathway controls cell proliferation, death and differentiation. Several families of extracellular proteins can antagonize Wnt/beta-catenin signaling, including the decoy receptors known as secreted frizzled related proteins (SFRPs), which have a cysteine-rich domain (CRD) structurally similar to the extracellular Wnt-binding domain of the frizzled receptors. SFRPs inhibit Wnt signaling by sequestering Wnts through the CRD or by forming inactive complexes with the frizzled receptors. Other endogenous molecules carrying frizzled CRDs inhibit Wnt signaling, such as V3Nter, which is proteolytically derived from the cell surface component collagen XVIII and contains a biologically active frizzled domain (FZC18) inhibiting in vivo cell proliferation and tumor growth in mice. We recently showed that FZC18 expressing cells deliver short-range signals to neighboring cells, decreasing their proliferation in vitro and in vivo through the Wnt/beta-catenin signaling pathway. Here, using low concentrations of soluble FZC18 and Wnt3a, we show that they physically interact in a cell-free system. In addition, soluble FZC18 binds the frizzled 1 and 8 receptors' CRDs, reducing cell sensitivity to Wnt3a. Conversely, inhibition of Wnt/beta-catenin signaling was partially rescued by the expression of full-length frizzled 1 and 8 receptors, but enhanced by the expression of a chimeric cell-membrane-tethered frizzled 8 CRD. Moreover, soluble, partially purified recombinant FZC18_CRD inhibited Wnt3a-induced beta catenin activation. Taken together, the data indicate that collagen XVIII-derived frizzled CRD shifts Wnt sensitivity of normal cells to a lower pitch and controls their growth. PMID- 22303446 TI - Increased GABA(A) receptor epsilon-subunit expression on ventral respiratory column neurons protects breathing during pregnancy. AB - GABAergic signaling is essential for proper respiratory function. Potentiation of this signaling with allosteric modulators such as anesthetics, barbiturates, and neurosteroids can lead to respiratory arrest. Paradoxically, pregnant animals continue to breathe normally despite nearly 100-fold increases in circulating neurosteroids. epsilon subunit-containing GABA(A)Rs are insensitive to positive allosteric modulation, thus we hypothesized that pregnant rats increase epsilon subunit-containing GABA(A)R expression on brainstem neurons of the ventral respiratory column (VRC). In vivo, pregnancy rendered respiratory motor output insensitive to otherwise lethal doses of pentobarbital, a barbiturate previously used to categorize the epsilon subunit. Using electrode array recordings in vitro, we demonstrated that putative respiratory neurons of the preBotzinger Complex (preBotC) were also rendered insensitive to the effects of pentobarbital during pregnancy, but unit activity in the VRC was rapidly inhibited by the GABA(A)R agonist, muscimol. VRC unit activity from virgin and post-partum females was potently inhibited by both pentobarbital and muscimol. Brainstem epsilon subunit mRNA and protein levels were increased in pregnant rats, and GABA(A)R epsilon subunit expression co-localized with a marker of rhythm generating neurons (neurokinin 1 receptors) in the preBotC. These data support the hypothesis that pregnancy renders respiratory motor output and respiratory neuron activity insensitive to barbiturates, most likely via increased epsilon subunit containing GABA(A)R expression on respiratory rhythm-generating neurons. Increased epsilon subunit expression may be critical to preserve respiratory function (and life) despite increased neurosteroid levels during pregnancy. PMID- 22303447 TI - Incidence of treatment-limiting toxicity with stavudine-based antiretroviral therapy in Cambodia: a retrospective cohort study. AB - BACKGROUND: Although stavudine (D4T) remains frequently used in low-income countries in Asia, associated long-term toxicity data are scarce. The aim of this study was to determine the long-term incidence of severe D4T-toxicity (requiring drug substitution) and associated risk factors in HIV-infected Cambodians up to six years on antiretroviral treatment (ART). METHODOLOGY/PRINCIPAL FINDINGS: This is a retrospective analysis of an observational cohort, using data from an ART program with systematic monitoring for D4T-toxicity. Probabilities of time to D4T substitution due to suspected D4T toxicity (treatment-limiting D4T toxicity) were calculated, a risk factor analysis was performed using multivariate Cox regression modelling. Out of 2581 adults initiating a D4T-containing regimen, D4T was replaced in 276 (10.7%) patients for neuropathy, 14 (0.5%) for lactic acidosis and 957 (37.1%) for lipoatrophy. The main early side effect was peripheral neuropathy (7.0% by 1 year). After the first year, lipoatrophy became predominant, with a cumulative incidence of 56.1% and 72.4% by 3 and 6 years respectively. Older age (aHR 1.8; 95%CI: 1.4-2.3) and lower baseline haemoglobin (aHR 1.7; 95%CI: 1.4-2.2) were associated with the occurrence of neuropathy. Being female (aHR 3.8; 95%CI: 1.1-12.5), a higher baseline BMI (aHR 12.6; 95%CI: 3.7-43.1), and TB treatment at ART initiation (aHR 8.6; 95%CI: 2.7-27.5) increased the likelihood of lactic acidosis. Lipoatrophy was positively associated with female gender (aHR 2.3; 95%CI: 2.0-2.6), an older age (aHR 1.3; 95%CI: 1.1-1.4), and a CD4 count <200 cells/uL (aHR 1.3; 95%CI: 1.1-1.5). CONCLUSIONS: Stavudine-based treatment regimens in low-income countries are associated with significant long-term toxicities, predominantly lipoatrophy. Close clinical monitoring for toxicity with timely D4T substitution is recommended. Phasing-out of stavudine should be implemented, as costs allows. PMID- 22303444 TI - A deeply branching thermophilic bacterium with an ancient acetyl-CoA pathway dominates a subsurface ecosystem. AB - A nearly complete genome sequence of Candidatus 'Acetothermum autotrophicum', a presently uncultivated bacterium in candidate division OP1, was revealed by metagenomic analysis of a subsurface thermophilic microbial mat community. Phylogenetic analysis based on the concatenated sequences of proteins common among 367 prokaryotes suggests that Ca. 'A. autotrophicum' is one of the earliest diverging bacterial lineages. It possesses a folate-dependent Wood-Ljungdahl (acetyl-CoA) pathway of CO(2) fixation, is predicted to have an acetogenic lifestyle, and possesses the newly discovered archaeal-autotrophic type of bifunctional fructose 1,6-bisphosphate aldolase/phosphatase. A phylogenetic analysis of the core gene cluster of the acethyl-CoA pathway, shared by acetogens, methanogens, some sulfur- and iron-reducers and dechlorinators, supports the hypothesis that the core gene cluster of Ca. 'A. autotrophicum' is a particularly ancient bacterial pathway. The habitat, physiology and phylogenetic position of Ca. 'A. autotrophicum' support the view that the first bacterial and archaeal lineages were H(2)-dependent acetogens and methanogenes living in hydrothermal environments. PMID- 22303448 TI - Consistent pattern of local adaptation during an experimental heat wave in a pipefish-trematode host-parasite system. AB - Extreme climate events such as heat waves are expected to increase in frequency under global change. As one indirect effect, they can alter magnitude and direction of species interactions, for example those between hosts and parasites. We simulated a summer heat wave to investigate how a changing environment affects the interaction between the broad-nosed pipefish (Syngnathus typhle) as a host and its digenean trematode parasite (Cryptocotyle lingua). In a fully reciprocal laboratory infection experiment, pipefish from three different coastal locations were exposed to sympatric and allopatric trematode cercariae. In order to examine whether an extreme climatic event disrupts patterns of locally adapted host parasite combinations we measured the parasite's transmission success as well as the host's adaptive and innate immune defence under control and heat wave conditions. Independent of temperature, sympatric cercariae were always more successful than allopatric ones, indicating that parasites are locally adapted to their hosts. Hosts suffered from heat stress as suggested by fewer cells of the adaptive immune system (lymphocytes) compared to the same groups that were kept at 18 degrees C. However, the proportion of the innate immune cells (monocytes) was higher in the 18 degrees C water. Contrary to our expectations, no interaction between host immune defence, parasite infectivity and temperature stress were found, nor did the pattern of local adaptation change due to increased water temperature. Thus, in this host-parasite interaction, the sympatric parasite keeps ahead of the coevolutionary dynamics across sites, even under increasing temperatures as expected under marine global warming. PMID- 22303449 TI - ISL1 directly regulates FGF10 transcription during human cardiac outflow formation. AB - The LIM homeodomain gene Islet-1 (ISL1) encodes a transcription factor that has been associated with the multipotency of human cardiac progenitors, and in mice enables the correct deployment of second heart field (SHF) cells to become the myocardium of atria, right ventricle and outflow tract. Other markers have been identified that characterize subdomains of the SHF, such as the fibroblast growth factor Fgf10 in its anterior region. While functional evidence of its essential contribution has been demonstrated in many vertebrate species, SHF expression of Isl1 has been shown in only some models. We examined the relationship between human ISL1 and FGF10 within the embryonic time window during which the linear heart tube remodels into four chambers. ISL1 transcription demarcated an anatomical region supporting the conserved existence of a SHF in humans, and transcription factors of the GATA family were co-expressed therein. In conjunction, we identified a novel enhancer containing a highly conserved ISL1 consensus binding site within the FGF10 first intron. ChIP and EMSA demonstrated its direct occupation by ISL1. Transcription mediated by ISL1 from this FGF10 intronic element was enhanced by the presence of GATA4 and TBX20 cardiac transcription factors. Finally, transgenic mice confirmed that endogenous factors bound the human FGF10 intronic enhancer to drive reporter expression in the developing cardiac outflow tract. These findings highlight the interest of examining developmental regulatory networks directly in human tissues, when possible, to assess candidate non-coding regions that may be responsible for congenital malformations. PMID- 22303450 TI - Optical imaging of disseminated leukemia models in mice with near-infrared probe conjugated to a monoclonal antibody. AB - BACKGROUND: The assessment of anticancer agents to treat leukemia needs to have animal models closer to the human pathology such as implantation in immunodeficient mice of leukemic cells from patient samples. A sensitive and early detection of tumor cells in these orthotopic models is a prerequisite for monitoring engraftment of leukemic cells and their dissemination in mice. Therefore, we developed a fluorescent antibody based strategy to detect leukemic foci in mice bearing patient-derived leukemic cells using fluorescence reflectance imaging (FRI) to determine when to start treatments with novel antitumor agents. METHODS: Two mAbs against the CD44 human myeloid marker or the CD45 human leukocyte marker were labeled with Alexa Fluor 750 and administered to leukemia-bearing mice after having verified the immunoreactivity in vitro. Bioluminescent leukemic cells (HL60-Luc) were used to compare the colocalization of the fluorescent mAb with these cells. The impact of the labeled antibodies on disease progression was further determined. Finally, the fluorescent hCD45 mAb was tested in mice engrafted with human leukemic cells. RESULTS: The probe labeling did not modify the immunoreactivity of the mAbs. There was a satisfactory correlation between bioluminescence imaging (BLI) and FRI and low doses of mAb were sufficient to detect leukemic foci. However, anti-hCD44 mAb had a strong impact on the tumor proliferation contrary to anti-hCD45 mAb. The use of anti-hCD45 mAb allowed the detection of leukemic patient cells engrafted onto NOD/SCID mice. CONCLUSIONS: A mAb labeled with a near infrared fluorochrome is useful to detect leukemic foci in disseminated models provided that its potential impact on tumor proliferation has been thoroughly documented. PMID- 22303451 TI - Nox4 mediates renal cell carcinoma cell invasion through hypoxia-induced interleukin 6- and 8- production. AB - BACKGROUND: Inflammatory cytokines are detected in the plasma of patients with renal cell carcinoma (RCC) and are associated with poor prognosis. However, the primary cell type involved in producing inflammatory cytokines and the biological significance in RCC remain unknown. Inflammation is associated with oxidative stress, upregulation of hypoxia inducible factor 1-alpha, and production of pro inflammatory gene products. Solid tumors are often heterogeneous in oxygen tension together suggesting that hypoxia may play a role in inflammatory processes in RCC. Epithelial cells have been implicated in cytokine release, although the stimuli to release and molecular mechanisms by which they are released remain unclear. AMP-activated protein kinase (AMPK) is a highly conserved sensor of cellular energy status and a role for AMPK in the regulation of cell inflammatory processes has recently been demonstrated. METHODS AND PRINCIPAL FINDINGS: We have identified for the first time that interleukin-6 and interleukin-8 (IL-6 and IL-8) are secreted solely from RCC cells exposed to hypoxia. Furthermore, we demonstrate that the NADPH oxidase isoform, Nox4, play a key role in hypoxia-induced IL-6 and IL-8 production in RCC. Finally, we have characterized that enhanced levels of IL-6 and IL-8 result in RCC cell invasion and that activation of AMPK reduces Nox4 expression, IL-6 and IL-8 production, and RCC cell invasion. CONCLUSIONS/SIGNIFICANCE: Together, our data identify novel mechanisms by which AMPK and Nox4 may be linked to inflammation-induced RCC metastasis and that pharmacological activation of AMPK and/or antioxidants targeting Nox4 may represent a relevant therapeutic intervention to reduce IL-6- and IL-8-induced inflammation and cell invasion in RCC. PMID- 22303452 TI - Quality control and performance of HIV rapid tests in a microbicide clinical trial in rural KwaZulu-Natal. AB - BACKGROUND: Quality control (QC) and evaluation of HIV rapid test procedures are an important aspect of HIV prevention trials. We describe QC and performance of two rapid tests, DetermineTM and Uni-GoldTM used in a microbicide clinical trial in rural KwaZulu-Natal, South Africa. METHODS/RESULTS: Internal QC of both HIV rapid tests was conducted at the trial site using a Uni-Gold control kit (Uni GoldTMRecombigen(r) HIV). Both assays produced the expected results for a total of 4637 QC tests. Study participants were tested for HIV at screening and, if enrolled, at regular time points throughout the study. Positive or discordant results were confirmed by a double HIV immunoassay testing strategy at a local laboratory. Overall, 15292 HIV rapid test were performed. Sensitivity and specificity of Determine was 98.95% (95% CI: 97.72-99.61) and 99.83% (95% CI: 99.70-99.91) respectively [positive predictive value (PPV) 97.91% (95% CI: 96.38 98.92)], for Uni-Gold it was 99.30% (95% CI: 98.21-99.81) and 99.96% (95% CI: 99.88-99.99) respectively [PPV 99.47% (95% CI: 98.46-99.89)]. CONCLUSIONS: The results suggest that a Uni-Gold control kit can be used for internal QC of both Uni-Gold and the HIV-1 component of the Determine rapid tests. Both rapid tests performed proficiently in the trial population. PMID- 22303453 TI - Catalog of microRNA seed polymorphisms in vertebrates. AB - MicroRNAs (miRNAs) are a class of non-coding RNA that plays an important role in posttranscriptional regulation of mRNA. Evidence has shown that miRNA gene variability might interfere with its function resulting in phenotypic variation and disease susceptibility. A major role in miRNA target recognition is ascribed to complementarity with the miRNA seed region that can be affected by polymorphisms. In the present study, we developed an online tool for the detection of miRNA polymorphisms (miRNA SNiPer) in vertebrates (http://www.integratomics-time.com/miRNA-SNiPer) and generated a catalog of miRNA seed region polymorphisms (miR-seed-SNPs) consisting of 149 SNPs in six species. Although a majority of detected polymorphisms were due to point mutations, two consecutive nucleotide substitutions (double nucleotide polymorphisms, DNPs) were also identified in nine miRNAs. We determined that miR-SNPs are frequently located within the quantitative trait loci (QTL), chromosome fragile sites, and cancer susceptibility loci, indicating their potential role in the genetic control of various complex traits. To test this further, we performed an association analysis between the mmu-miR-717 seed SNP rs30372501, which is polymorphic in a large number of standard inbred strains, and all phenotypic traits in these strains deposited in the Mouse Phenome Database. Analysis showed a significant association between the mmu-miR-717 seed SNP and a diverse array of traits including behavior, blood-clinical chemistry, body weight size and growth, and immune system suggesting that seed SNPs can indeed have major pleiotropic effects. The bioinformatics analyses, data and tools developed in the present study can serve researchers as a starting point in testing more targeted hypotheses and designing experiments using optimal species or strains for further mechanistic studies. PMID- 22303454 TI - Seeing emotion with your ears: emotional prosody implicitly guides visual attention to faces. AB - Interpersonal communication involves the processing of multimodal emotional cues, particularly facial expressions (visual modality) and emotional speech prosody (auditory modality) which can interact during information processing. Here, we investigated whether the implicit processing of emotional prosody systematically influences gaze behavior to facial expressions of emotion. We analyzed the eye movements of 31 participants as they scanned a visual array of four emotional faces portraying fear, anger, happiness, and neutrality, while listening to an emotionally-inflected pseudo-utterance (Someone migged the pazing) uttered in a congruent or incongruent tone. Participants heard the emotional utterance during the first 1250 milliseconds of a five-second visual array and then performed an immediate recall decision about the face they had just seen. The frequency and duration of first saccades and of total looks in three temporal windows ([0-1250 ms], [1250-2500 ms], [2500-5000 ms]) were analyzed according to the emotional content of faces and voices. Results showed that participants looked longer and more frequently at faces that matched the prosody in all three time windows (emotion congruency effect), although this effect was often emotion-specific (with greatest effects for fear). Effects of prosody on visual attention to faces persisted over time and could be detected long after the auditory information was no longer present. These data imply that emotional prosody is processed automatically during communication and that these cues play a critical role in how humans respond to related visual cues in the environment, such as facial expressions. PMID- 22303455 TI - Time-lapse imaging of the dynamics of CNS glial-axonal interactions in vitro and ex vivo. AB - BACKGROUND: Myelination is an exquisite and dynamic example of heterologous cell cell interaction, which consists of the concentric wrapping of multiple layers of oligodendrocyte membrane around neuronal axons. Understanding the mechanism by which oligodendrocytes ensheath axons may bring us closer to designing strategies to promote remyelination in demyelinating diseases. The main aim of this study was to follow glial-axonal interactions over time both in vitro and ex vivo to visualize the various stages of myelination. METHODOLOGY/PRINCIPAL FINDINGS: We took two approaches to follow myelination over time: i) time-lapse imaging of mixed CNS myelinating cultures generated from mouse spinal cord to which exogenous GFP-labelled murine cells were added, and ii) ex vivo imaging of the spinal cord of shiverer (Mbp mutant) mice, transplanted with GFP-labelled murine neurospheres. We demonstrate that oligodendrocyte-axonal interactions are dynamic events with continuous retraction and extension of oligodendroglial processes. Using cytoplasmic and membrane-GFP labelled cells to examine different components of the myelin-like sheath, we provide evidence from time-lapse fluorescence microscopy and confocal microscopy that the oligodendrocytes' cytoplasm-filled processes initially spiral around the axon in a corkscrew-like manner. This is followed subsequently by focal expansion of the corkscrew process to form short cuffs, which then extend longitudinally along the axons. We predict from this model that these spiral cuffs must extend over each other first before extending to form internodes of myelin. CONCLUSION: These experiments show the feasibility of visualizing the dynamics of glial-axonal interaction during myelination over time. Moreover, these approaches complement each other with the in vitro approach allowing visualization of an entire internodal length of myelin and the ex vivo approach validating the in vitro data. PMID- 22303456 TI - ERK1 regulates the hematopoietic stem cell niches. AB - The mitogen-activated protein kinases (MAPK) ERK1 and ERK2 are among the major signal transduction molecules but little is known about their specific functions in vivo. ERK activity is provided by two isoforms, ERK1 and ERK2, which are ubiquitously expressed and share activators and substrates. However, there are not in vivo studies which have reported a role for ERK1 or ERK2 in HSCs and the bone marrow microenvironment. The present study shows that the ERK1-deficient mice present a mild osteopetrosis phenotype. The lodging and the homing abilities of the ERK1(-/-) HSC are impaired, suggesting that the ERK1(-/-)-defective environment may affect the engrafment of HSCs. Serial transplantations demonstrate that ERK1 is involved in the maintenance of an appropriate medullar microenvironment, but that the intrinsic properties of HSCs are not altered by the ERK1(-/-) defective microenvironment. Deletion of ERK1 impaired in vitro and in vivo osteoclastogenesis while osteoblasts were unaffected. As osteoclasts derive from precursors of the monocyte/macrophage lineage, investigation of the monocytic compartment was performed. In vivo analysis of the myeloid lineage progenitors revealed that the frequency of CMPs increased by approximately 1.3 fold, while the frequency of GMPs significantly decreased by almost 2-fold, compared with the respective WT compartments. The overall mononuclear-phagocyte lineage development was compromised in these mice due to a reduced expression of the M-CSF receptor on myeloid progenitors. These results show that the cellular targets of ERK1 are M-CSFR-responsive cells, upstream to osteoclasts. While ERK1 is well known to be activated by M-CSF, the present results are the first to point out an ERK1-dependent M-CSFR regulation on hematopoietic progenitors. This study reinforces the hypothesis of an active cross-talk between HSCs, their progeny and bone cells in the maintenance of the homeostasis of these compartments. PMID- 22303457 TI - Reliability and validity of simplified Chinese version of Roland-Morris questionnaire in evaluating rural and urban patients with low back pain. AB - OBJECTIVE: The causes of low back pain in China and Western countries are extremely different. We attempted to analyze the risk factors of low back pain in urban and rural patients under the dual economy with the simplified Chinese version of Roland-Morris disability questionnaire (SC-RMDQ) to demonstrate that SC-RMDQ could evaluate patients with low back pain arising from different causes. METHODS: Roland-Morris disability questionnaire was translated into SCRMDQ according to international guidelines for questionnaire adaptation. In this study, causes of low back pain of 187 outpatients and inpatients (99 urban patients and 88 rural patients) were analyzed. All patients underwent simplified Chinese version of Roland-Morris disability questionnaire (SC-RMDQ), simplified Chinese Oswestry disability index (SCODI) and visual analogue scale (VAS). Reliability was tested using reproducibility (intraclass coefficient of correlation--ICC) and internal consistency (Cronbach's alpha). Validity was tested using Pearson correlation analysis. RESULTS: The leading causes for low back pain were sedentariness (38.4%) and vibration (18.1%) in urban patients and waist bending (48.9%) and spraining (25%) in rural patients. Although causes of low back pain in the two groups of population were completely different, SCRMDQ had high internal consistency (Cronbach's alpha value of 0.874 in urban patients and 0.883 in rural patients) and good reproducibility (ICC value of .952 in urban patients and 0.949 in rural patients, P<0.01). SCRMDQ also showed significant correlation with Simplified Chinese version of Oswestry disability index (SCODI) and visual analogue scale (VAS) in rural areas (SCRMDQ-SCODI r = 0.841; SCRMDQ VAS: r = 0.685, P<0.01) and in urban areas (SCRMDQ-SCODI: r = 0.818, P<0.01; SCRMDQ-VAS: r = 0.666, P<0.01). CONCLUSIONS: Although causes of low back pain are completely different in rural and urban patients, SCRMDQ has a good reliability and validity, which is a reliable clinical method to evaluate disability of rural and urban patients. PMID- 22303458 TI - Automated workflow for preparation of cDNA for cap analysis of gene expression on a single molecule sequencer. AB - BACKGROUND: Cap analysis of gene expression (CAGE) is a 5' sequence tag technology to globally determine transcriptional starting sites in the genome and their expression levels and has most recently been adapted to the HeliScope single molecule sequencer. Despite significant simplifications in the CAGE protocol, it has until now been a labour intensive protocol. METHODOLOGY: In this study we set out to adapt the protocol to a robotic workflow, which would increase throughput and reduce handling. The automated CAGE cDNA preparation system we present here can prepare 96 'HeliScope ready' CAGE cDNA libraries in 8 days, as opposed to 6 weeks by a manual operator.We compare the results obtained using the same RNA in manual libraries and across multiple automation batches to assess reproducibility. CONCLUSIONS: We show that the sequencing was highly reproducible and comparable to manual libraries with an 8 fold increase in productivity. The automated CAGE cDNA preparation system can prepare 96 CAGE sequencing samples simultaneously. Finally we discuss how the system could be used for CAGE on Illumina/SOLiD platforms, RNA-seq and full-length cDNA generation. PMID- 22303459 TI - Activation of Wnt signaling by chemically induced dimerization of LRP5 disrupts cellular homeostasis. AB - Wnt signaling is crucial for a variety of biological processes, including body axis formation, planar polarity, stem cell maintenance and cellular differentiation. Therefore, targeted manipulation of Wnt signaling in vivo would be extremely useful. By applying chemical inducer of dimerization (CID) technology, we were able to modify the Wnt co-receptor, low-density lipoprotein (LDL)-receptor-related protein 5 (LRP5), to generate the synthetic ligand inducible Wnt switch, iLRP5. We show that iLRP5 oligomerization results in its localization to disheveled-containing punctate structures and sequestration of scaffold protein Axin, leading to robust beta-catenin-mediated signaling. Moreover, we identify a novel LRP5 cytoplasmic domain critical for its intracellular localization and casein kinase 1-dependent beta-catenin signaling. Finally, by utilizing iLRP5 as a Wnt signaling switch, we generated the Ubiquitous Activator of beta-catenin (Ubi-Cat) transgenic mouse line. The Ubi-Cat line allows for nearly ubiquitous expression of iLRP5 under control of the H 2K(b) promoter. Activation of iLRP5 in isolated prostate basal epithelial stem cells resulted in expansion of p63(+) cells and development of hyperplasia in reconstituted murine prostate grafts. Independently, iLRP5 induction in adult prostate stroma enhanced prostate tissue regeneration. Moreover, induction of iLRP5 in male Ubi-Cat mice resulted in prostate tumor progression over several months from prostate hyperplasia to adenocarcinoma. We also investigated iLRP5 activation in Ubi-Cat-derived mammary cells, observing that prolonged activation results in mammary tumor formation. Thus, in two distinct experimental mouse models, activation of iLRP5 results in disruption of tissue homeostasis, demonstrating the utility of iLRP5 as a novel research tool for determining the outcome of Wnt activation in a precise spatially and temporally determined fashion. PMID- 22303460 TI - Class I histone deacetylase inhibitor entinostat suppresses regulatory T cells and enhances immunotherapies in renal and prostate cancer models. AB - BACKGROUND: Immunosuppressive factors such as regulatory T cells (Tregs) limit the efficacy of immunotherapies. Histone deacetylase (HDAC) inhibitors have been reported to have antitumor activity in different malignancies and immunomodulatory effects. Herein, we report the Tregs-targeting and immune promoting effect of a class I specific HDAC inhibitor, entinostat, in combination with either IL-2 in a murine renal cell carcinoma (RENCA) model or a survivin based vaccine therapy (SurVaxM) in a castration resistant prostate cancer (CR Myc CaP) model. METHODS AND RESULTS: RENCA or CR Myc-CaP tumors were implanted orthotopically or subcutaneously, respectively. Inoculated mice were randomized into four treatment groups: vehicle, entinostat, cytokine or vaccine, and combination. Tregs in the blood were assessed by FACS analysis. Real time quantitative PCR and Western blot analysis of isolated T cell subpopulations from spleen were performed to determine Foxp3 gene and protein expression. The suppressive function of Tregs was tested by T cell proliferation assay. Low dose (5 mg/kg) entinostat reduced Foxp3 levels in Tregs and this was associated with enhanced tumor growth inhibition in combination with either IL-2 or a SurVaxM vaccine. Entinostat down-regulated Foxp3 expression transcriptionally and blocked Tregs suppressive function without affecting T effector cells (Teffs). In vitro low dose entinostat (0.5 uM) induced STAT3 acetylation and a specific inhibitor of STAT3 partially rescued entinostat-induced down-regulation of Foxp3, suggesting that STAT3 signaling is involved in Foxp3 down-regulation by entinostat. CONCLUSIONS: These results demonstrate a novel immunomodulatory effect of class I HDAC inhibition and provide a rationale for the clinical testing of entinostat to enhance cancer immunotherapy. PMID- 22303461 TI - LRRK2 phosphorylates tubulin-associated tau but not the free molecule: LRRK2 mediated regulation of the tau-tubulin association and neurite outgrowth. AB - Leucine-rich repeat kinase 2 (LRRK2), a large protein kinase containing multi functional domains, has been identified as the causal molecule for autosomal dominant Parkinson's disease (PD). In the present study, we demonstrated for the first time that (i) LRRK2 interacts with tau in a tubulin-dependent manner; (ii) LRRK2 directly phosphorylates tubulin-associated tau, but not free tau; (iii) LRRK2 phosphorylates tau at Thr181 as one of the target sites; and (iv) The PD associated LRRK2 mutations, G2019S and I2020T, elevated the degree of tau phosphorylation. These results provide direct proof that tau is a physiological substrate for LRRK2. Furthermore, we revealed that LRRK2-mediated phosphorylation of tau reduces its tubulin-binding ability. Our results suggest that LRRK2 plays an important role as a physiological regulator for phosphorylation-mediated dissociation of tau from microtubules, which is an integral aspect of microtubule dynamics essential for neurite outgrowth and axonal transport. PMID- 22303462 TI - Coxiella burnetii induces apoptosis during early stage infection via a caspase independent pathway in human monocytic THP-1 cells. AB - The ability of Coxiella burnetii to modulate host cell death may be a critical factor in disease development. In this study, human monocytic THP-1 cells were used to examine the ability of C. burnetii Nine Mile phase II (NMII) to modulate apoptotic signaling. Typical apoptotic cell morphological changes and DNA fragmentation were detected in NMII infected cells at an early stage of infection. FACS analysis using Annexin-V-PI double staining showed the induction of a significant number of apoptotic cells at an early stage of NMII infection. Double staining of apoptotic cell DNA and intracellular C. burnetii indicates that NMII infected cells undergoing apoptosis. Interestingly, caspase-3 was not cleaved in NMII infected cells and the caspase-inhibitor Z-VAD-fmk did not prevent NMII induced apoptosis. Surprisingly, the caspase-3 downstream substrate PARP was cleaved in NMII infected cells. These results suggest that NMII induces apoptosis during an early stage of infection through a caspase-independent pathway in THP-1 cells. In addition, NMII-infected monocytes were unable to prevent exogenous staurosporine-induced apoptotic death. Western blot analysis indicated that NMII infection induced the translocation of AIF from mitochondria into the nucleus. Cytochrome c release and cytosol-to-mitochondrial translocation of the pore-forming protein Bax in NMII infected cells occurred at 24 h post infection. These data suggest that NMII infection induced caspase-independent apoptosis through a mechanism involving cytochrome c release, cytosol-to mitochondrial translocation of Bax and nuclear translocation of AIF in THP-1 monocytes. Furthermore, NMII infection increased TNF-alpha production and neutralization of TNF-alpha in NMII infected cells partially blocked PARP cleavage, suggesting TNF-alpha may play a role in the upstream signaling involved in NMII induced apoptosis. Antibiotic inhibition of C. burnetii RNA synthesis blocked NMII infection-induced PARP activation. These results suggest that both intracellular C. burnetii replication and secreted TNF-alpha contribute to NMII infection-triggered apoptosis during an early stage of infection. PMID- 22303463 TI - Nipah virus infects specific subsets of porcine peripheral blood mononuclear cells. AB - Nipah virus (NiV), a zoonotic paramyxovirus, is highly contagious in swine, and can cause fatal infections in humans following transmission from the swine host. The main viral targets in both species are the respiratory and central nervous systems, with viremia implicated as a mode of dissemination of NiV throughout the host. The presented work focused on the role of peripheral blood mononuclear cells (PBMC) in the viremic spread of the virus in the swine host. B lymphocytes, CD4-CD8-, as well as CD4+CD8- T lymphocytes were not permissive to NiV, and expansion of the CD4+CD8- cells early post infection was consistent with functional humoral response to NiV infection observed in swine. In contrast, significant drop in the CD4+CD8- T cell frequency was observed in piglets which succumbed to the experimental infection, supporting the hypothesis that antibody development is the critical component of the protective immune response. Productive viral replication was detected in monocytes, CD6+CD8+ T lymphocytes and NK cells by recovery of infectious virus in the cell supernatants. Virus replication was supported by detection of the structural N and the non-structural C proteins or by detection of genomic RNA increase in the infected cells. Infection of T cells carrying CD6 marker, a strong ligand for the activated leukocyte cell adhesion molecule ALCAM (CD166) highly expressed on the microvascular endothelial cell of the blood-air and the blood-brain barrier may explain NiV preferential tropism for small blood vessels of the lung and brain. PMID- 22303464 TI - Transcriptome profiling of sexual maturation and mating in the Mediterranean fruit fly, Ceratitis capitata. AB - Sexual maturation and mating in insects are generally accompanied by major physiological and behavioural changes. Many of these changes are related to the need to locate a mate and subsequently, in the case of females, to switch from mate searching to oviposition behaviour. The prodigious reproductive capacity of the Mediterranean fruit fly, Ceratitis capitata, is one of the factors that has led to its success as an invasive pest species. To identify the molecular changes related to maturation and mating status in male and female medfly, a microarray based gene expression approach was used to compare the head transcriptomes of sexually immature, mature virgin, and mated individuals. Attention was focused on the changes in abundance of transcripts related to reproduction, behaviour, sensory perception of chemical stimulus, and immune system processes. Broad transcriptional changes were recorded during female maturation, while post-mating transcriptional changes in females were, by contrast, modest. In male medfly, transcriptional changes were consistent both during maturation and as a consequence of mating. Of particular note was the lack of the mating-induced immune responses that have been recorded for Drosophila melanogaster, that may be due to the different reproductive strategies of these species. This study, in addition to increasing our understanding of the molecular machinery behind maturation and mating in the medfly, has identified important gene targets that might be useful in the future management of this pest. PMID- 22303465 TI - Portable optical fiber probe-based spectroscopic scanner for rapid cancer diagnosis: a new tool for intraoperative margin assessment. AB - There continues to be a significant clinical need for rapid and reliable intraoperative margin assessment during cancer surgery. Here we describe a portable, quantitative, optical fiber probe-based, spectroscopic tissue scanner designed for intraoperative diagnostic imaging of surgical margins, which we tested in a proof of concept study in human tissue for breast cancer diagnosis. The tissue scanner combines both diffuse reflectance spectroscopy (DRS) and intrinsic fluorescence spectroscopy (IFS), and has hyperspectral imaging capability, acquiring full DRS and IFS spectra for each scanned image pixel. Modeling of the DRS and IFS spectra yields quantitative parameters that reflect the metabolic, biochemical and morphological state of tissue, which are translated into disease diagnosis. The tissue scanner has high spatial resolution (0.25 mm) over a wide field of view (10 cm * 10 cm), and both high spectral resolution (2 nm) and high spectral contrast, readily distinguishing tissues with widely varying optical properties (bone, skeletal muscle, fat and connective tissue). Tissue-simulating phantom experiments confirm that the tissue scanner can quantitatively measure spectral parameters, such as hemoglobin concentration, in a physiologically relevant range with a high degree of accuracy (<5% error). Finally, studies using human breast tissues showed that the tissue scanner can detect small foci of breast cancer in a background of normal breast tissue. This tissue scanner is simpler in design, images a larger field of view at higher resolution and provides a more physically meaningful tissue diagnosis than other spectroscopic imaging systems currently reported in literatures. We believe this spectroscopic tissue scanner can provide real-time, comprehensive diagnostic imaging of surgical margins in excised tissues, overcoming the sampling limitation in current histopathology margin assessment. As such it is a significant step in the development of a platform technology for intraoperative management of cancer, a clinical problem that has been inadequately addressed to date. PMID- 22303466 TI - Ashwagandha derived withanone targets TPX2-Aurora A complex: computational and experimental evidence to its anticancer activity. AB - Cancer is largely marked by genetic instability. Specific inhibition of individual proteins or signalling pathways that regulate genetic stability during cell division thus hold a great potential for cancer therapy. The Aurora A kinase is a Ser/Thr kinase that plays a critical role during mitosis and cytokinesis and is found upregulated in several cancer types. It is functionally regulated by its interactions with TPX2, a candidate oncogene. Aurora A inhibitors have been proposed as anticancer drugs that work by blocking its ATP binding site. This site is common to other kinases and hence these inhibitors lack specificity for Aurora A inhibition in particular, thus advocating the need of some alternative inhibition route. Previously, we identified TPX2 as a cellular target for withanone that selectively kill cancer cells. By computational approach, we found here that withanone binds to TPX2-Aurora A complex. In experiment, withanone treatment to cancer cells indeed resulted in dissociation of TPX2-Aurora A complex and disruption of mitotic spindle apparatus proposing this as a mechanism of the anticancer activity of withanone. From docking analysis, non formation/disruption of the active TPX2-Aurora A association complex could be discerned. Our MD simulation results suggesting the thermodynamic and structural stability of TPX2-Aurora A in complex with withanone further substantiates the binding. We report a computational rationale of the ability of naturally occurring withanone to alter the kinase signalling pathway in an ATP-independent manner and experimental evidence in which withanone cause inactivation of the TPX2-Aurora A complex. The study demonstrated that TPX2-Aurora A complex is a target of withanone, a potential natural anticancer drug. PMID- 22303467 TI - pitx2 Deficiency results in abnormal ocular and craniofacial development in zebrafish. AB - Human PITX2 mutations are associated with Axenfeld-Rieger syndrome, an autosomal dominant developmental disorder that involves ocular anterior segment defects, dental hypoplasia, craniofacial dysmorphism and umbilical abnormalities. Characterization of the PITX2 pathway and identification of the mechanisms underlying the anomalies associated with PITX2 deficiency is important for better understanding of normal development and disease; studies of pitx2 function in animal models can facilitate these analyses. A knockdown of pitx2 in zebrafish was generated using a morpholino that targeted all known alternative transcripts of the pitx2 gene; morphant embryos generated with the pitx2(ex4/5) splicing blocking oligomer produced abnormal transcripts predicted to encode truncated pitx2 proteins lacking the third (recognition) helix of the DNA-binding homeodomain. The morphological phenotype of pitx2(ex4/5) morphants included small head and eyes, jaw abnormalities and pericardial edema; lethality was observed at ~6-8-dpf. Cartilage staining revealed a reduction in size and an abnormal shape/position of the elements of the mandibular and hyoid pharyngeal arches; the ceratobranchial arches were also decreased in size. Histological and marker analyses of the misshapen eyes of the pitx2(ex4/5) morphants identified anterior segment dysgenesis and disordered hyaloid vasculature. In summary, we demonstrate that pitx2 is essential for proper eye and craniofacial development in zebrafish and, therefore, that PITX2/pitx2 function is conserved in vertebrates. PMID- 22303468 TI - Busulphan-cyclophosphamide cause endothelial injury, remodeling of resistance arteries and enhanced expression of endothelial nitric oxide synthase. AB - Stem cell transplantation (SCT) is a curative treatment for malignant and non malignant diseases. However, transplantation-related complications including cardiovascular disease deteriorate the clinical outcome and quality of life. We have investigated the acute effects of conditioning regimen on the pharmacology, physiology and structure of large elastic arteries and small resistance-sized arteries in a SCT mouse model. Mesenteric resistance arteries and aorta were dissected from Balb/c mice conditioned with busulphan (Bu) and cyclophosphamide (Cy). In vitro isometric force development and pharmacology, in combination with RT-PCR, Western blotting and electron microscopy were used to study vascular properties. Compared with controls, mesenteric resistance arteries from the Bu-Cy group had larger internal circumference, showed enhanced endothelium mediated relaxation and increased expression of endothelial nitric oxide synthase (eNOS). Bu-Cy treated animals had lower mean blood pressure and signs of endothelial injury. Aortas of treated animals had a higher reactivity to noradrenaline. We conclude that short-term consequences of Bu-Cy treatment divergently affect large and small arteries of the cardiovascular system. The increased noradrenaline reactivity of large elastic arteries was not associated with increased blood pressure at rest. Instead, Bu-Cy treatment lowered blood pressure via augmented microvascular endothelial dependent relaxation, increased expression of vascular eNOS and remodeling toward a larger lumen. The changes in the properties of resistance arteries can be associated with direct effects of the compounds on vascular wall or possibly indirectly induced via altered translational activity associated with the reduced hematocrit and shear stress. This study contributes to understanding the mechanisms that underlie the early effects of conditioning regimen on resistance arteries and may help in designing further investigations to understand the late effects on vascular system. PMID- 22303469 TI - Induction of heterosubtypic cross-protection against influenza by a whole inactivated virus vaccine: the role of viral membrane fusion activity. AB - BACKGROUND: The inability of seasonal influenza vaccines to effectively protect against infection with antigenically drifted viruses or newly emerging pandemic viruses underlines the need for development of cross-reactive influenza vaccines that induce immunity against a variety of virus subtypes. Therefore, potential cross-protective vaccines, e.g., whole inactivated virus (WIV) vaccine, that can target conserved internal antigens such as the nucleoprotein (NP) and/or matrix protein (M1) need to be explored. METHODOLOGY/PRINCIPAL FINDINGS: In the current study we show that a WIV vaccine, through induction of cross-protective cytotoxic T lymphocytes (CTLs), protects mice from heterosubtypic infection. This protection was abrogated after depletion of CD8+ cells in vaccinated mice, indicating that CTLs were the primary mediators of protection. Previously, we have shown that different procedures used for virus inactivation influence optimal activation of CTLs by WIV, most likely by affecting the membrane fusion properties of the virus. Specifically, inactivation with formalin (FA) severely compromises fusion activity of the virus, while inactivation with beta propiolactone (BPL) preserves fusion activity. Here, we demonstrate that vaccination of mice with BPL-inactivated H5N1 WIV vaccine induces solid protection from lethal heterosubtypic H1N1 challenge. By contrast, vaccination with FA-inactivated WIV, while preventing death after lethal challenge, failed to protect against development of disease and severe body weight loss. Vaccination with BPL-inactivated WIV, compared to FA-inactivated WIV, induced higher levels of specific CD8+ T cells in blood, spleen and lungs, and a higher production of granzyme B in the lungs upon H1N1 virus challenge. CONCLUSION/SIGNIFICANCE: The results underline the potential use of WIV as a cross-protective influenza vaccine candidate. However, careful choice of the virus inactivation procedure is important to retain membrane fusion activity and full immunogenicity of the vaccine. PMID- 22303470 TI - Hyperbilirubinemia and neurodevelopmental outcome of very low birthweight infants: results from the LIFT cohort. AB - BACKGROUND: Bilirubin-related neurotoxicity is an important clinical issue in very low birthweight (VLBW) infants, and the existing literature is inconsistent. OBJECTIVE: To analyze the relationship between maximal serum unconjugated bilirubin levels (SBL) and neurodevelopmental outcome at 2-year corrected age in VLBW infants. METHODS: Phototherapy was initiated in all infants born before 33 weeks of gestation, according to Maisels' recommendations. Neurodevelopmental assessment at 2-year corrected age was performed in all infants that survived. SBLs collected during the first week of life were used to define three tertiles of max-SBL. The first tertile corresponded to infants with the lowest max-SBL. RESULTS AND CONCLUSIONS: A total of 724 infants were included in the study, and among them, 631 (87%) were evaluated at two years old. The infants of the first tertile were younger and smaller than the infants of the other two tertiles, in accordance with Maisels' recommendations for very small infants. No difference in the risk of impaired functional outcome among the three groups was observed. However, among infants weighing less than 1001 g, those in the third tertile had a poorer neurodevelopmental prognosis as compared to those in the second tertile (adjusted odds ratio = 6.8, 95% CI: 1.2-36.7, p = 0.03). Considering the results obtained, we propose 196 umol/L (11.5 mg/dL) when birthweight varies between 1001 and 1500 g, and 170 umol/L (9.9 mg/dL) when birthweight is less than 1001 g, as recommended max-SBLs (defined as maximal levels of 95(th) percentile curves of SBLs in infants with an optimal outcome). When Maisels' recommendations were applied, max SBLs were higher in 8% of infants weighing 1001-1500 g and in 15% of infants weighing less than 1001 g. Our data seems to validate Maisels' recommendations in the overall population of infants born before 33 weeks of gestation, but not in infants weighing less than 1001 g. PMID- 22303471 TI - Early cell death detection with digital holographic microscopy. AB - BACKGROUND: Digital holography provides a non-invasive measurement of the quantitative phase shifts induced by cells in culture, which can be related to cell volume changes. It has been shown previously that regulation of cell volume, in particular as it relates to ionic homeostasis, is crucially involved in the activation/inactivation of the cell death processes. We thus present here an application of digital holographic microscopy (DHM) dedicated to early and label free detection of cell death. METHODS AND FINDINGS: We provide quantitative measurements of phase signal obtained on mouse cortical neurons, and caused by early neuronal cell volume regulation triggered by excitotoxic concentrations of L-glutamate. We show that the efficiency of this early regulation of cell volume detected by DHM, is correlated with the occurrence of subsequent neuronal death assessed with the widely accepted trypan blue method for detection of cell viability. CONCLUSIONS: The determination of the phase signal by DHM provides a simple and rapid optical method for the early detection of cell death. PMID- 22303472 TI - Identification and profiling of microRNAs from skeletal muscle of the common carp. AB - The common carp is one of the most important cultivated species in the world of freshwater aquaculture. The cultivation of this species is particularly productive due to its high skeletal muscle mass; however, the molecular mechanisms of skeletal muscle development in the common carp remain unknown. It has been shown that a class of non-coding ~22 nucleotide RNAs called microRNAs (miRNAs) play important roles in vertebrate development. They regulate gene expression through sequence-specific interactions with the 3' untranslated regions (UTRs) of target mRNAs and thereby cause translational repression or mRNA destabilization. Intriguingly, the role of miRNAs in the skeletal muscle development of the common carp remains unknown. In this study, a small-RNA cDNA library was constructed from the skeletal muscle of the common carp, and Solexa sequencing technology was used to perform high throughput sequencing of the library. Subsequent bioinformatics analysis identified 188 conserved miRNAs and 7 novel miRNAs in the carp skeletal muscle. The miRNA expression profiling showed that, miR-1, miR-133a-3p, and miR-206 were specifically expressed in muscle containing organs, and that miR-1, miR-21, miR-26a, miR-27a, miR-133a-3p, miR 206, miR-214 and miR-222 were differentially expressed in the process of skeletal muscle development of the common carp. This study provides a first identification and profiling of miRNAs related to the muscle biology of the common carp. Their identification could provide clues leading towards a better understanding of the molecular mechanisms of carp skeletal muscle development. PMID- 22303473 TI - Does a family meetings intervention prevent depression and anxiety in family caregivers of dementia patients? A randomized trial. AB - BACKGROUND: Family caregivers of dementia patients are at increased risk of developing depression or anxiety. A multi-component program designed to mobilize support of family networks demonstrated effectiveness in decreasing depressive symptoms in caregivers. However, the impact of an intervention consisting solely of family meetings on depression and anxiety has not yet been evaluated. This study examines the preventive effects of family meetings for primary caregivers of community-dwelling dementia patients. METHODS: A randomized multicenter trial was conducted among 192 primary caregivers of community dwelling dementia patients. Caregivers did not meet the diagnostic criteria for depressive or anxiety disorder at baseline. Participants were randomized to the family meetings intervention (n = 96) or usual care (n = 96) condition. The intervention consisted of two individual sessions and four family meetings which occurred once every 2 to 3 months for a year. Outcome measures after 12 months were the incidence of a clinical depressive or anxiety disorder and change in depressive and anxiety symptoms (primary outcomes), caregiver burden and quality of life (secondary outcomes). Intention-to-treat as well as per protocol analyses were performed. RESULTS: A substantial number of caregivers (72/192) developed a depressive or anxiety disorder within 12 months. The intervention was not superior to usual care either in reducing the risk of disorder onset (adjusted IRR 0.98; 95% CI 0.69 to 1.38) or in reducing depressive (randomization-by-time interaction coefficient = -1.40; 95% CI -3.91 to 1.10) or anxiety symptoms (randomization-by-time interaction coefficient = -0.55; 95% CI -1.59 to 0.49). The intervention did not reduce caregiver burden or their health related quality of life. CONCLUSION: This study did not demonstrate preventive effects of family meetings on the mental health of family caregivers. Further research should determine whether this intervention might be more beneficial if provided in a more concentrated dose, when applied for therapeutic purposes or targeted towards subgroups of caregivers. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN90163486. PMID- 22303474 TI - The efficacy of exercise in reducing depressive symptoms among cancer survivors: a meta-analysis. AB - INTRODUCTION: The purpose of this meta-analysis was to examine the efficacy of exercise to reduce depressive symptoms among cancer survivors. In addition, we examined the extent to which exercise dose and clinical characteristics of cancer survivors influence the relationship between exercise and reductions in depressive symptoms. METHODS: We conducted a systematic search identifying randomized controlled trials of exercise interventions among adult cancer survivors, examining depressive symptoms as an outcome. We calculated effect sizes for each study and performed weighted multiple regression moderator analysis. RESULTS: We identified 40 exercise interventions including 2,929 cancer survivors. Diverse groups of cancer survivors were examined in seven exercise interventions; breast cancer survivors were examined in 26; prostate cancer, leukemia, and lymphoma were examined in two; and colorectal cancer in one. Cancer survivors who completed an exercise intervention reduced depression more than controls, d(+) = -0.13 (95% CI: -0.26, -0.01). Increases in weekly volume of aerobic exercise reduced depressive symptoms in dose-response fashion (beta = 0.24, p = 0.03), a pattern evident only in higher quality trials. Exercise reduced depressive symptoms most when exercise sessions were supervised (beta = 0.26, p = 0.01) and when cancer survivors were between 47-62 yr (beta = 0.27, p = 0.01). CONCLUSION: Exercise training provides a small overall reduction in depressive symptoms among cancer survivors but one that increased in dose response fashion with weekly volume of aerobic exercise in high quality trials. Depressive symptoms were reduced to the greatest degree among breast cancer survivors, among cancer survivors aged between 47-62 yr, or when exercise sessions were supervised. PMID- 22303476 TI - International technology transfer of a GCLP-compliant HIV-1 neutralizing antibody assay for human clinical trials. AB - The Collaboration for AIDS Vaccine Discovery/Comprehensive Antibody-Vaccine Immune Monitoring Consortium (CAVD/CA-VIMC) assisted an international network of laboratories in transferring a validated assay used to judge HIV-1 vaccine immunogenicity in compliance with Good Clinical Laboratory Practice (GCLP) with the goal of adding quality to the conduct of endpoint assays for Human Immunodeficiency Virus I (HIV-1) vaccine human clinical trials. Eight Regional Laboratories in the international setting (Regional Laboratories), many located in regions where the HIV-1 epidemic is most prominent, were selected to implement the standardized, GCLP-compliant Neutralizing Antibody Assay for HIV-1 in TZM-bl Cells (TZM-bl NAb Assay). Each laboratory was required to undergo initial training and implementation of the immunologic assay on-site and then perform partial assay re-validation, competency testing, and undergo formal external audits for GCLP compliance. Furthermore, using a newly established external proficiency testing program for the TZM-bl NAb Assay has allowed the Regional Laboratories to assess the comparability of assay results at their site with the results of neutralizing antibody assays performed around the world. As a result, several of the CAVD/CA-VIMC Regional Laboratories are now in the process of conducting or planning to conduct the GCLP-compliant TZM-bl NAb Assay as an indicator of vaccine immunogenicity for ongoing human clinical trials. PMID- 22303475 TI - A role for VEGFR2 activation in endothelial responses caused by barrier disruptive OxPAPC concentrations. AB - INTRODUCTION: Oxidation products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3 phosphatidylcholine (OxPAPC) differentially modulate endothelial cell (EC) barrier function in a dose-dependent fashion. Vascular endothelial growth factor receptor-2 (VEGFR2) is involved in the OxPAPC-induced EC inflammatory activation. This study examined a role of VEGFR2 in barrier dysfunction caused by high concentrations of OxPAPC and evaluated downstream signaling mechanisms resulting from the effect of OxPAPC in EC from pulmonary and systemic circulation. METHODS: EC monolayer permeability in human pulmonary artery endothelial cells (HPAEC) and human aortic endothelial cells (HAEC) was monitored by changes in transendothelial electrical resistance (TER) across EC monolayers. Actin cytoskeleton was examined by immunostaining with Texas Red labeled phalloidin. Phosphorylation of myosin light chains (MLC) and VE-Cadherin was examined by Western blot and immunofluorescence techniques. The role of VEGFR2 in OxPAPC induced permeability and cytoskeletal arrangement were determined using siRNA induced VEGFR2 knockdown. RESULTS: Low OxPAPC concentrations (5-20 ug/ml) induced a barrier protective response in both HPAEC and HAEC, while high OxPAPC concentrations (50-100 ug/ml) caused a rapid increase in permeability; actin stress fiber formation and increased MLC phosphorylation were observed as early as 30 min after treatment. VEGFR2 knockdown dramatically decreased the amount of MLC phosphorylation and stress fiber formation caused by high OxPAPC concentrations with modest effects on the amount of VE-cadherin phosphorylation at Y(731). We present evidence that activation of Rho is involved in the OxPAPC/VEGFR2 mechanism of EC permeability induced by high OxPAPC concentrations. Knockdown of VEGFR2 did not rescue the early drop in TER but prevented further development of OxPAPC-induced barrier dysfunction. CONCLUSIONS: This study shows that VEGFR2 is involved in the delayed phase of EC barrier dysfunction caused by high OxPAPC concentrations and contributes to stress fiber formation and increased MLC phosphorylation. PMID- 22303477 TI - Interactive effects of large- and small-scale sources of feral honey-bees for sunflower in the Argentine Pampas. AB - Pollinators for animal pollinated crops can be provided by natural and semi natural habitats, ranging from large vegetation remnants to small areas of non crop land in an otherwise highly modified landscape. It is unknown, however, how different small- and large-scale habitat patches interact as pollinator sources. In the intensively managed Argentine Pampas, we studied the additive and interactive effects of large expanses (up to 2200 ha) of natural habitat, represented by untilled isolated "sierras", and narrow (3-7 m wide) strips of semi-natural habitat, represented by field margins, as pollinator sources for sunflower (Helianthus annus). We estimated visitation rates by feral honey-bees, Apis mellifera, and native flower visitors (as a group) at 1, 5, 25, 50 and 100 m from a field margin in 17 sunflower fields 0-10 km distant from the nearest sierra. Honey-bees dominated the pollinator assemblage accounting for >90% of all visits to sunflower inflorescences. Honey-bee visitation was strongly affected by proximity to the sierras decreasing by about 70% in the most isolated fields. There was also a decline in honey-bee visitation with distance from the field margin, which was apparent with increasing field isolation, but undetected in fields nearby large expanses of natural habitat. The probability of observing a native visitor decreased with isolation from the sierras, but in other respects visitation by flower visitors other than honey-bees was mostly unaffected by the habitat factors assessed in this study. Overall, we found strong hierarchical and interactive effects between the study large and small-scale pollinator sources. These results emphasize the importance of preserving natural habitats and managing actively field verges in the absence of large remnants of natural habitat for improving pollinator services. PMID- 22303478 TI - Reorganizing the intrinsic functional architecture of the human primary motor cortex during rest with non-invasive cortical stimulation. AB - The primary motor cortex (M1) is the main effector structure implicated in the generation of voluntary movements and is directly involved in motor learning. The intrinsic horizontal neuronal connections of M1 exhibit short-term and long-term plasticity, which is a strong substrate for learning-related map reorganization. Transcranial direct current stimulation (tDCS) applied for few minutes over M1 has been shown to induce relatively long-lasting plastic alterations and to modulate motor performance. Here we test the hypothesis that the relatively long lasting synaptic modification induced by tDCS over M1 results in the alteration of associations among populations of M1 neurons which may be reflected in changes of its functional architecture. fMRI resting-state datasets were acquired immediately before and after 10 minutes of tDCS during rest, with the anode/cathode placed over the left M1. For each functional dataset, grey-matter voxels belonging to Brodmann area 4 (BA4) were labelled and afterwards BA4 voxel based synchronization matrices were calculated and thresholded to construct undirected graphs. Nodal network parameters which characterize the architecture of functional networks (connectivity degree, clustering coefficient and characteristic path-length) were computed, transformed to volume maps and compared before and after stimulation. At the dorsolateral-BA4 region cathodal tDCS boosted local connectedness, while anodal-tDCS enhanced long distance functional communication within M1. Additionally, the more efficient the functional architecture of M1 was at baseline, the more efficient the tDCS induced functional modulations were. In summary, we show here that it is possible to non-invasively reorganize the intrinsic functional architecture of M1, and to image such alterations. PMID- 22303479 TI - Piwil2 suppresses p53 by inducing phosphorylation of signal transducer and activator of transcription 3 in tumor cells. AB - Piwi proteins have been implicated in germ cell proliferation, differentiation, germline stem cell maintenance and transposon control in germline from Drosophila to mammals. The Piwi-like2 (piwil2) gene is mainly expressed in testis or embryonic cells among normal tissues but widely expressed in tumors. However, it remains to be fully determined through which mechanism piwil2 is involved in tumorigenesis. Here we report that Human piwil2, or Hili represses the tumor suppressor P53 in human cancer cells. Immunoprecipitation analysis shows that Piwil2 can directly associate with Signal Transducer and Activator of Transcription 3 (STAT3) protein via its PAZ domain and form a Piwil2/STAT3/c-Src triple protein-protein complex. Furthermore, STAT3 is phosphorylated by c-Src and translocated to nucleus, then binds to P53 promoter and represses its transcription. The present study demonstrated that Piwil2 plays a role in anti apoptosis in tumor cells possessing P53 as a positive regulator of STAT3 signaling pathway, providing novel sights into roles of Piwil2 in tumorigenesis. PMID- 22303480 TI - PKCtheta synergizes with TLR-dependent TRAF6 signaling pathway to upregulate MUC5AC mucin via CARMA1. AB - CARD-containing MAGUK protein 1 (CARMA1) plays a crucial role in regulating adaptive immune responses upon T-cell receptor (TCR) activation in T cells. Its role in regulating host mucosal innate immune response such as upregulation of mucin remains unknown. Here we show that CARMA1 acts as a key signaling mediator for synergistic upregulation of MUC5AC mucin by bacterium nontypeable Haemophilus influenzae (NTHi) and phorbol ester PMA in respiratory epithelial cells. NTHi induced TLR-dependent TRAF6-MKK3-p38 MAPK signaling pathway synergizes with PKCtheta-MEK-ERK signaling pathway. CARMA1 plays a crucial role in mediating this synergistic effect via TRAF6, thereby resulting in synergistic upregulation of MUC5AC mucin. Thus our study unveils a novel role for CARMA1 in mediating host mucosal innate immune response. PMID- 22303481 TI - An ensemble classifier for eukaryotic protein subcellular location prediction using gene ontology categories and amino acid hydrophobicity. AB - With the rapid increase of protein sequences in the post-genomic age, it is challenging to develop accurate and automated methods for reliably and quickly predicting their subcellular localizations. Till now, many efforts have been tried, but most of which used only a single algorithm. In this paper, we proposed an ensemble classifier of KNN (k-nearest neighbor) and SVM (support vector machine) algorithms to predict the subcellular localization of eukaryotic proteins based on a voting system. The overall prediction accuracies by the one versus-one strategy are 78.17%, 89.94% and 75.55% for three benchmark datasets of eukaryotic proteins. The improved prediction accuracies reveal that GO annotations and hydrophobicity of amino acids help to predict subcellular locations of eukaryotic proteins. PMID- 22303482 TI - TBX21 and HLX1 polymorphisms influence cytokine secretion at birth. AB - BACKGROUND: TBX21 (T cell specific T-box transcription factor) and HLX1 (H.20 like homeobox 1) are crucial transcription factors of T(H)1-cells, inducing their differentiation and suppressing T(H)2 commitment, particularly important for early life immune development. This study investigated the influence of TBX21 and HLX1 single nucleotide polymorphisms (SNPs), which have previously been shown to be associated with asthma, on T(H)1/T(H)2 lineage cytokines at birth. METHODS AND FINDINGS: Cord blood mononuclear cells (CBMCs) of 200 neonates were genotyped for two TBX21 and three HLX1 SNPs. CBMCs were stimulated with innate (Lipid A, LpA; Peptidoglycan, Ppg), adaptive stimuli (house dust mite Dermatophagoides pteronyssinus 1, Derp1) or mitogen (phytohemagglutinin, PHA). Cytokines, T-cells and mRNA expression of T(H)1/T(H)2-related genes were assessed. Atopic diseases during the first 3 years of life were assessed by questionnaire answered by the parents. Carriers of TBX21 promoter SNP rs17250932 and HLX1 promoter SNP rs2738751 showed reduced or trendwise reduced (p<=0.07) IL-5, IL-13 and TNF-alpha secretion after LpA-stimulation. Carriers of HLX1 SNP rs2738751 had lower IL-13 levels following Ppg-stimulation (p = 0.08). Carriers of HLX1 exon 1 SNP rs12141189 showed increased IL-5 (LpA, p = 0.007; Ppg, p = 0.10), trendwise increased IL-13 (LpA), higher GM-CSF (LpA/Ppg, p<=0.05) and trendwise decreased IFN-gamma secretion (Derp1+LpA-stimulation, p = 0.1). Homozygous carriers of HLX1 promoter SNP rs3806325 showed increased IL-13 and IL-6 (unstimulated, p<=0.03). In carriers of TBX21 intron 3 SNP rs11079788 no differences in cytokine secretion were observed. mRNA expression of T(H)1/T(H)2-related genes partly correlated with cytokines at protein level. TBX21 SNP rs11079788 carriers developed less symptoms of atopic dermatitis at 3 years of age (p = 0.03). CONCLUSIONS: Polymorphisms in TBX21 and HLX1 influenced primarily IL-5 and IL-13 secretion after LpA-stimulation in cord blood suggesting that genetic variations in the transcription factors essential for the T(H)1-pathway may contribute to modified T(H)2-immune responses already early in life. Further follow-up of the cohort is required to study the polymorphisms' relevance for immune-mediated diseases such as childhood asthma. PMID- 22303483 TI - Diminished social motivation negatively impacts reputation management: autism spectrum disorders as a case in point. AB - Human beings are endowed with a unique motivation to be included in social interactions. This natural social motivation, in turn, is thought to encourage behaviours such as flattery or self-deprecation aimed to ease interaction and to enhance the reputation of the individual who produces them. If this is the case, diminished social interest should affect reputation management. Here, we use Autism Spectrum Disorders (ASDs)--primarily characterised by pervasive social disinterest--as a model to investigate the effect of social motivation on reputation management. Children first rated a set of pictures and were then given the opportunity to inflate their initial ratings in front of an experimenter who declared that she had drawn the picture. Contrary to the controls, children with ASD did not enhance their ratings in the drawer's presence. Moreover, participants' flattery behaviour correlated with self-reports of social enjoyment. Our findings point to a link between diminished social interest and reputation management. PMID- 22303484 TI - Novel, objective, multivariate biomarkers composed of plasma amino acid profiles for the diagnosis and assessment of inflammatory bowel disease. AB - BACKGROUND: Inflammatory bowel disease (IBD) is a chronic intestinal disorder that is associated with a limited number of clinical biomarkers. In order to facilitate the diagnosis of IBD and assess its disease activity, we investigated the potential of novel multivariate indexes using statistical modeling of plasma amino acid concentrations (aminogram). METHODOLOGY AND PRINCIPAL FINDINGS: We measured fasting plasma aminograms in 387 IBD patients (Crohn's disease (CD), n = 165; ulcerative colitis (UC), n = 222) and 210 healthy controls. Based on Fisher linear classifiers, multivariate indexes were developed from the aminogram in discovery samples (CD, n = 102; UC, n = 102; age and sex-matched healthy controls, n = 102) and internally validated. The indexes were used to discriminate between CD or UC patients and healthy controls, as well as between patients with active disease and those in remission. We assessed index performances using the area under the curve of the receiver operating characteristic (ROC AUC). We observed significant alterations to the plasma aminogram, including histidine and tryptophan. The multivariate indexes established from plasma aminograms were able to distinguish CD or UC patients from healthy controls with ROC AUCs of 0.940 (95% confidence interval (CI): 0.898 0.983) and 0.894 (95%CI: 0.853-0.935), respectively in validation samples (CD, n = 63; UC, n = 120; healthy controls, n = 108). In addition, other indexes appeared to be a measure of disease activity. These indexes distinguished active CD or UC patients from each remission patients with ROC AUCs of 0.894 (95%CI: 0.853-0.935) and 0.849 (95%CI: 0.770-0.928), and correlated with clinical disease activity indexes for CD (r(s) = 0.592, 95%CI: 0.385-0.742, p<0.001) or UC (r(s) = 0.598, 95%CI: 0.452-0.713, p<0.001), respectively. CONCLUSIONS AND SIGNIFICANCE: In this study, we demonstrated that established multivariate indexes composed of plasma amino acid profiles can serve as novel, non-invasive, objective biomarkers for the diagnosis and monitoring of IBD, providing us with new insights into the pathophysiology of the disease. PMID- 22303485 TI - Simulated warming differentially affects the growth and competitive ability of Centaurea maculosa populations from home and introduced ranges. AB - Climate warming may drive invasions by exotic plants, thereby raising concerns over the risks of invasive plants. However, little is known about how climate warming influences the growth and competitive ability of exotic plants from their home and introduced ranges. We conducted a common garden experiment with an invasive plant Centaurea maculosa and a native plant Poa pratensis, in which a mixture of sand and vermiculite was used as a neutral medium, and contrasted the total biomass, competitive effects, and competitive responses of C. maculosa populations from Europe (home range) and North America (introduced range) under two different temperatures. The warming-induced inhibitory effects on the growth of C. maculosa alone were stronger in Europe than in North America. The competitive ability of C. maculosa plants from North America was greater than that of plants from Europe under the ambient condition whereas this competitive ability followed the opposite direction under the warming condition, suggesting that warming may enable European C. maculosa to be more invasive. Across two continents, warming treatment increased the competitive advantage instead of the growth advantage of C. maculosa, suggesting that climate warming may facilitate C. maculosa invasions through altering competitive outcomes between C. maculosa and its neighbors. Additionally, the growth response of C. maculosa to warming could predict its ability to avoid being suppressed by its neighbors. PMID- 22303486 TI - The risk of stroke after percutaneous vertebroplasty for osteoporosis: a population-based cohort study. AB - PURPOSE: To investigate the incidence and risk of stroke after percutaneous vertebroplasty in patients with osteoporosis. METHODS: A group of 334 patients with osteoporosis, and who underwent percutaneous vertebroplasty during the study period, was compared to 1,655 age-, sex- and propensity score-matched patients who did not undergo vertebroplasty. All demographic covariates and co-morbidities were deliberately matched between the two groups to avoid selection bias. Every subject was followed-up for up to five years for stroke. Adjustments using a Cox regression model and Kaplan-Meier analyses were conducted. RESULTS: A total of 1,989 osteoporotic patients were followed up for 3,760.13 person-years. Overall, the incidence rates of any stroke, hemorrhagic stroke and ischemic stroke were 22.6, 4.2 and 19.6 per 1,000 person-years, respectively. Patients who underwent vertebroplasty were not more likely to have any stroke (crude hazard ratio = 1.13, p = 0.693), hemorrhagic stroke (HR = 2.21, p = 0.170), or ischemic stroke (HR = 0.96, p = 0.90). After adjusting for demographics, co-morbidities and medications, the vertebroplasty group had no significant difference with the comparison group in terms of any, hemorrhagic and ischemic strokes (adjusted HR = 1.22, 3.17, and 0.96, p = 0.518, 0.055, and 0.91, respectively). CONCLUSIONS: Osteoporotic patients who undergo percutaneous vertebroplasty are not at higher risk of any stroke in the next five years after the procedure. PMID- 22303487 TI - Relative Effectiveness of Reading Intervention Programs for Adults with Low Literacy. AB - To compare the efficacy of instructional programs for adult learners with basic reading skills below the seventh grade level, 300 adults were randomly assigned to one of three supplementary tutoring programs designed to strengthen decoding and fluency skills, and gains were examined for the 148 adult students who completed the program. The three intervention programs were based on or adapted from instructional programs that have been shown to benefit children with reading levels similar to those of the adult sample. Each program varied in its relative emphasis on basic decoding versus reading fluency instruction. A repeated measures MANOVA confirmed small to moderate reading gains from pre- to post testing across a battery of targeted reading measures, but no significant relative differences across interventions. An additional 152 participants who failed to complete the intervention differed initially from those who persisted. Implications for future research and adult literacy instruction are discussed. PMID- 22303488 TI - Comparative study of rK39 Leishmania antigen for serodiagnosis of visceral leishmaniasis: systematic review with meta-analysis. AB - BACKGROUND: The rK39 recombinant protein is derived from a specific antigen produced by the Leishmania donovani complex, and has been used in the last two decades for the serodiagnosis of visceral leishmaniasis. We present here a systematic review and meta-analysis of studies evaluating serologic assays to diagnose visceral leishmaniasis to determine the accuracy of rK39 antigen in comparison to the use of other antigen preparations. METHODOLOGY/PRINCIPAL FINDINGS: A systematic review with meta-analysis of the literature was performed to compare the rK39 strip-test and ELISA formats against serological tests using promastigote antigens derived from whole or soluble parasites for Direct Aglutination Test (DAT), Indirect Immunofluorescence test (IFAT) and ELISA with a promastigote antigen preparation (p-ELISA). Gold standard diagnosis was defined by the demonstration of amastigotes on hematological specimens. A database search was performed on Medline, Lilacs, Scopus, Isi Web of Science, and Cochrane Library. Quality of data was assessed using the QUADAS questionnaire. A search of the electronic databases found 352 papers of which only 14 fulfilled the selection criteria. Three evaluated the rK39 ELISA, while 13 evaluated the rK39 immunochromatographic strip test. The summarized sensitivity for the rK39-ELISA was 92% followed by IFAT 88% and p-ELISA 87%. The summarized specificity for the three diagnostic tests was 81%, 90%, and 77%. Studies comparing the rK39 strip test with DAT found a similar sensitivity of 94%, although the DAT had a slightly higher specificity. The rK39 strip test was more sensitive and specific than the IFAT and p-ELISA. We did not detect any difference in the sensitivity and specificity between strips produced by different manufacturers. CONCLUSIONS: The rK39 protein used either in a strip test or in an ELISA, and the DAT are the best choices for implementation of rapid, easy and efficient test for serodiagnosis of VL. PMID- 22303489 TI - Melioidosis vaccines: a systematic review and appraisal of the potential to exploit biodefense vaccines for public health purposes. AB - BACKGROUND: Burkholderia pseudomallei is a Category B select agent and the cause of melioidosis. Research funding for vaccine development has largely considered protection within the biothreat context, but the resulting vaccines could be applicable to populations who are at risk of naturally acquired melioidosis. Here, we discuss target populations for vaccination, consider the cost-benefit of different vaccination strategies and review potential vaccine candidates. METHODS AND FINDINGS: Melioidosis is highly endemic in Thailand and northern Australia, where a biodefense vaccine might be adopted for public health purposes. A cost effectiveness analysis model was developed, which showed that a vaccine could be a cost-effective intervention in Thailand, particularly if used in high-risk populations such as diabetics. Cost-effectiveness was observed in a model in which only partial immunity was assumed. The review systematically summarized all melioidosis vaccine candidates and studies in animal models that had evaluated their protectiveness. Possible candidates included live attenuated, whole cell killed, sub-unit, plasmid DNA and dendritic cell vaccines. Live attenuated vaccines were not considered favorably because of possible reversion to virulence and hypothetical risk of latent infection, while the other candidates need further development and evaluation. Melioidosis is acquired by skin inoculation, inhalation and ingestion, but routes of animal inoculation in most published studies to date do not reflect all of this. We found a lack of studies using diabetic models, which will be central to any evaluation of a melioidosis vaccine for natural infection since diabetes is the most important risk factor. CONCLUSION: Vaccines could represent one strand of a public health initiative to reduce the global incidence of melioidosis. PMID- 22303490 TI - Silent circulation of St. Louis encephalitis virus prior to an encephalitis outbreak in Cordoba, Argentina (2005). AB - St. Louis encephalitis virus is a complex zoonoses. In 2005, 47 laboratory confirmed and probable clinical cases of SLEV infection were reported in Cordoba, Argentina. Although the causes of 2005 outbreak remain unknown, they might be related not only to virological factors, but also to ecological and environmental conditions. We hypothesized that one of the factors for SLE reemergence in Cordoba, Argentina, was the introduction of a new SLEV genotype (SLEV genotype III), with no previous activity in the area. In order to evaluate this hypothesis we carried out a molecular characterization of SLEV detections from mosquitoes collected between 2001 and 2004 in Cordoba city. A total of 315 mosquito pools (11,002 individuals) including 12 mosquitoes species were analyzed. Overall, 20 pools (8 mosquitoes species) were positive for SLEV. During this study, genotypes II, V and VII were detected. No mosquito pool infected with genotype III was detected before the 2005 outbreak. Genotype V was found every year and in the 8 sampled sites. Genotypes II and VII showed limited temporal and spatial activities. We cannot dismiss the association of genotype II and V as etiological agents during the outbreak. However, the silent circulation of other SLEV strains in Cordoba city before the 2005 outbreak suggests that the introduction of genotype III was an important factor associated to this event. Not mutually exclusive, other factors such as changes in avian hosts and mosquitoes vectors communities, driven by climatic and environmental modifications, should also be taken into consideration in further studies. PMID- 22303491 TI - High-resolution genotyping of the endemic Salmonella Typhi population during a Vi (typhoid) vaccination trial in Kolkata. AB - BACKGROUND: Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a major health problem especially in developing countries. Vaccines against typhoid are commonly used by travelers but less so by residents of endemic areas. METHODOLOGY: We used single nucleotide polymorphism (SNP) typing to investigate the population structure of 372 S. Typhi isolated during a typhoid disease burden study and Vi vaccine trial in Kolkata, India. Approximately sixty thousand people were enrolled for fever surveillance for 19 months prior to, and 24 months following, Vi vaccination of one third of the study population (May 2003-December 2006, vaccinations given December 2004). PRINCIPAL FINDINGS: A diverse S. Typhi population was detected, including 21 haplotypes. The most common were of the H58 haplogroup (69%), which included all multidrug resistant isolates (defined as resistance to chloramphenicol, ampicillin and co trimoxazole). Quinolone resistance was particularly high among H58-G isolates (97% Nalidixic acid resistant, 30% with reduced susceptibility to ciprofloxacin). Multiple typhoid fever episodes were detected in 22 households, however household clustering was not associated with specific S. Typhi haplotypes. CONCLUSIONS: Typhoid fever in Kolkata is caused by a diverse population of S. Typhi, however H58 haplotypes dominate and are associated with multidrug and quinolone resistance. Vi vaccination did not obviously impact on the haplotype population structure of the S. Typhi circulating during the study period. PMID- 22303492 TI - Cognitive changes and quality of life in neurocysticercosis: a longitudinal study. AB - BACKGROUND: Few studies have focused on the cognitive morbidity of neurocysticercosis (NCC), one of the most common parasitic infections of the central nervous system. We longitudinally assessed the cognitive status and quality of life (QoL) of patients with incident symptomatic NCC cases and matched controls. METHODOLOGY/PRINCIPAL FINDINGS: The setting of the study was the Sabogal Hospital and Cysticercosis Unit, Department of Transmissible Diseases, National Institute of Neurological Sciences, Lima, Peru. The design was a longitudinal study of new onset NCC cases and controls. Participants included a total of 14 patients with recently diagnosed NCC along with 14 healthy neighborhood controls and 7 recently diagnosed epilepsy controls. A standardized neuropsychological battery was performed at baseline and at 6 months on NCC cases and controls. A brain MRI was performed in patients with NCC at baseline and 6 months. Neuropsychological results were compared between NCC cases and controls at both time points. At baseline, patients with NCC had lower scores on attention tasks (p<0.04) compared with epilepsy controls but no significant differences compared to healthy controls. Six months after receiving anti-parasitic treatment, the NCC group significantly improved on tasks involving psychomotor speed (p<0.02). QoL at baseline suggested impaired mental function and social function in both the NCC and epilepsy group compared with healthy controls. QoL gains in social function (p=0.006) were noted at 6 months in patients with NCC. CONCLUSIONS/SIGNIFICANCE: Newly diagnosed patients with NCC in this sample had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment. PMID- 22303493 TI - WormAssay: a novel computer application for whole-plate motion-based screening of macroscopic parasites. AB - Lymphatic filariasis is caused by filarial nematode parasites, including Brugia malayi. Adult worms live in the lymphatic system and cause a strong immune reaction that leads to the obstruction of lymph vessels and swelling of the extremities. Chronic disease leads to the painful and disfiguring condition known as elephantiasis. Current drug therapy is effective against the microfilariae (larval stage) of the parasite, but no drugs are effective against the adult worms. One of the major stumbling blocks toward developing effective macrofilaricides to kill the adult worms is the lack of a high throughput screening method for candidate drugs. Current methods utilize systems that measure one well at a time and are time consuming and often expensive. We have developed a low-cost and simple visual imaging system to automate and quantify screening entire plates based on parasite movement. This system can be applied to the study of many macroparasites as well as other macroscopic organisms. PMID- 22303494 TI - Control using genetically modified insects poses problems for regulators. PMID- 22303495 TI - Appropriate regulation of GM insects. PMID- 22303496 TI - Using molecular data for epidemiological inference: assessing the prevalence of Trypanosoma brucei rhodesiense in tsetse in Serengeti, Tanzania. AB - BACKGROUND: Measuring the prevalence of transmissible Trypanosoma brucei rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessing human disease risk and monitoring spatio-temporal trends and the impact of control interventions. Although an important epidemiological variable, identifying flies which carry transmissible infections is difficult, with challenges including low prevalence, presence of other trypanosome species in the same fly, and concurrent detection of immature non-transmissible infections. Diagnostic tests to measure the prevalence of T. b. rhodesiense in tsetse are applied and interpreted inconsistently, and discrepancies between studies suggest this value is not consistently estimated even to within an order of magnitude. METHODOLOGY/PRINCIPAL FINDINGS: Three approaches were used to estimate the prevalence of transmissible Trypanosoma brucei s.l. and T. b. rhodesiense in Glossina swynnertoni and G. pallidipes in Serengeti National Park, Tanzania: (i) dissection/microscopy; (ii) PCR on infected tsetse midguts; and (iii) inference from a mathematical model. Using dissection/microscopy the prevalence of transmissible T. brucei s.l. was 0% (95% CI 0-0.085) for G. swynnertoni and 0% (0-0.18) G. pallidipes; using PCR the prevalence of transmissible T. b. rhodesiense was 0.010% (0-0.054) and 0.0089% (0-0.059) respectively, and by model inference 0.0064% and 0.00085% respectively. CONCLUSIONS/SIGNIFICANCE: The zero prevalence result by dissection/microscopy (likely really greater than zero given the results of other approaches) is not unusual by this technique, often ascribed to poor sensitivity. The application of additional techniques confirmed the very low prevalence of T. brucei suggesting the zero prevalence result was attributable to insufficient sample size (despite examination of 6000 tsetse). Given the prohibitively high sample sizes required to obtain meaningful results by dissection/microscopy, PCR-based approaches offer the current best option for assessing trypanosome prevalence in tsetse but inconsistencies in relating PCR results to transmissibility highlight the need for a consensus approach to generate meaningful and comparable data. PMID- 22303497 TI - Science, regulation, and precedent for genetically modified insects. PMID- 22303498 TI - Detection of Mycobacterium ulcerans in the environment predicts prevalence of Buruli ulcer in Benin. AB - BACKGROUND: Mycobacterium ulcerans is the causative agent of Buruli ulcer (BU). In West Africa there is an association between BU and residence in low-lying rural villages where aquatic sources are plentiful. Infection occurs through unknown environmental exposure; human-to-human infection is rare. Molecular evidence for M. ulcerans in environmental samples is well documented, but the association of M. ulcerans in the environment with Buruli ulcer has not been studied in West Africa in an area with accurate case data. METHODOLOGY/PRINCIPAL FINDING: Environmental samples were collected from twenty-five villages in three communes of Benin. Sites sampled included 12 BU endemic villages within the Ouheme and Couffo River drainages and 13 villages near the Mono River and along the coast or ridge where BU has never been identified. Triplicate water filtrand samples from major water sources and samples from three dominant aquatic plant species were collected. Detection of M. ulcerans was based on quantitative polymerase chain reaction. Results show a significant association between M. ulcerans in environmental samples and Buruli ulcer cases in a village (p = 0.0001). A "dose response" was observed in that increasing numbers of M. ulceran- positive environmental samples were associated with increasing prevalence of BU cases (R(2) = 0.586). CONCLUSIONS/SIGNIFICANCE: This study provides the first spatial data on the overlap of M. ulcerans in the environment and BU cases in Benin where case data are based on active surveillance. The study also provides the first evidence on M. ulcerans in well-defined non-endemic sites. Most environmental pathogens are more broadly distributed in the environment than in human populations. The congruence of M. ulcerans in the environment and human infection raises the possibility that humans play a role in the ecology of M. ulcerans. Methods developed could be useful for identifying new areas where humans may be at high risk for BU. PMID- 22303499 TI - Electronic Medical Record System: Have we Bitten off More Than we Can Chew? PMID- 22303500 TI - Skin substitutes: a brief review of types and clinical applications. AB - Replacing skin defects has witnessed several developments over the centuries. It started with the introduction of skin grafting by Reverdin in 1871. Since then, varieties of skin grafting techniques have been used successfully. Despite being clinically useful, skin grafts have many limitations including the availability of the donor site especially in circumstances of extensive skin loss, immune rejection in allogenic skin grafts, pain, scarring, slow healing and infection.(1,2) For these reasons, scientist have worked hard to find skin substitutes to replace skin defects without the need for a "natural" skin graft. These materials which are used to cover skin defects are called "Skin substitutes". This article briefly discusses the common types of skin substitutes and their clinical uses. PMID- 22303501 TI - A simple technique of inserting an intra-abdominal drain in laparoscopic surgery. AB - OBJECTIVES: We describe a simple technique for introducing any size of intra abdominal drain in laparoscopy through a 3-5 mm port site without any of the drawbacks of other techniques practiced. METHODS: Setting is usually of a conventional laparoscopic surgery with various ports positioned depending on the procedure performed. At the end of theprocedure a 5 mm port site cannula is usually chosen to 'pull in' an intra-abdominal drain by railroading, under vision. RESULTS: Railroading method of insertion of intra-abdominal drain in laparoscopy is always successful with no failure rate and no associated complications. CONCLUSION: When indicated, this is the simplest method of inserting an intra-abdominal drain after laparoscopic surgery. PMID- 22303502 TI - Assessment of visual gain following cataract surgeries in oman: a hospital-based cohort study. AB - OBJECTIVES: The post-operative vision is used as benchmark to determine the quality of cataract surgery. However, late presentation and co-morbidities influence the visual gain and they should also be considered while auditing cataract surgeries. The authors present method of analysis of cataract surgeries for older than 30 years of aged patients performed by ophthalmologists in Oman during 2003. METHODS: Ophthalmologists evaluated visual and ocular status of eyes with cataract. Cataract was operated using operative microscope and lens was implanted in the eye. The vision was recorded six weeks after surgery and visual gain was grouped from postoperative vision in relation to the preoperative vision. Presence of co-morbidities like glaucoma, corneal opacities, macular degenerations and others were considered while evaluating visual outcomes. RESULTS: 3,485 eyes operated were included in our study. 3,003 (86.2%) of them were operated by extra-capsular cataract extraction and lens implantation. Following surgery, 960 (27.5%) eyes had vision 36/18. 1,483 (42.6%) eyes had vision between 6/60 and 6/18. 233 (6.8%) eyes had vision <3/60. Excellent grade of vision gain in relation to preoperative visual status was found in 2,250 (64.6%) eyes, 'good' visual gain was in 422 (12.1%) eyes and 'poor' visual gain was in 335 (9.6%) eyes. Postoperative visual status was significantly associated to the co-morbidities. (p<0.001). Nearly 14% of persons were lost to the follow up. CONCLUSION: In countries like Oman with high prevalence of trachoma, glaucoma and diabetes, the proposed grading of visual gain that accounts for the preoperative vision and the presence of co-morbidity could be better option for auditing the cataract surgery. PMID- 22303503 TI - A Study of Prescribing Valsartan in Out-patient Clinics at the Royal Hospital, Muscat, Oman. AB - OBJECTIVES: Angiotensin Receptor Blockers such as Valsartan, are a newer class of drugs associated with significant reductions in cardiovascular morbidity and mortality. They are commonly used in hypertension, chronic heart failure, diabetes-related nephropathy and post-myocardial infarction in patients who are intolerant to Angiotensin Converting Enzyme inhibitors (ACEi). A review of medicines used in Royal Hospital (an Omani tertiary health care centre) during 2004 and 2005 showed that Valsartan was one of 20 most expensive drugs used. The main objective of this study was to evaluate the pattern of prescribing valsartan in out-patient clinics. METHODS: a retrospective study, applying medicines use evaluation, to describe the pattern of prescribing Valsartan in comparison with international guidelines. The study carried out in the outpatient pharmacy setting, Royal Hospital from 15th May to 30th June 2006. It included 120 adult patients who had been prescribed Valsartan at the outpatient clinics during the study period. RESULTS: among the 120 patients only 109 patients were finally included in the study. Elevenpatients who had had duplicated prescriptionswere excluded from the study. 78% of the patients were on Valsartan for its FDA approved indications while 22% of patients were for other non-approved indications. Half of the patients were initiated on an ACEi before shifting to Valsartan. The other half of the patients was started with Valsartan as a first line choice without any clinical justification. CONCLUSION: The study showed that half of the patients were initiated on Valsartan without being prescribed an ACEi prior to that, while the recommendation in most of the international guidelines based on indication stated that ARBs are used in patients who are intolerant to ACEi. The study emphasizes the need for further research to highlight the need for developing national guidelines and adhering to these guidelines for rational prescribing. PMID- 22303504 TI - Predictors of positive chest radiography in non-traumatic chest pain in the emergency department. AB - OBJECTIVES: To determine predictors associated with positive chest x-ray finding in patients presenting with non-traumatic chest pain in the Emergency Department (ED). METHODS: Health records, including the final radiology reports of all patients who presented with non-traumatic chest pain and had a chest x-ray performed in an urban Canadian tertiary care ED over four consecutive months were reviewed. Demographic and clinical variables were also extracted. Chest x-ray findings were categorized as normal (either normal or no significant change from previous x-rays) or abnormal. Descriptive statistics were used to describe the data. Multivariable logistic regression was used to determine the association between various predictors and chest x-ray finding (positive/negative). RESULTS: The 330 study patients had the following characteristics: mean age 58+/-20 years; female 41% (n=134). Patients' chief complaints were only chest pain 75% (n=248), chest pain with shortness of breath 12% (n=41), chest pain with palpitation 4% (n=14), chest pain with other complaints 9% (n=28). Chest x-rays were reported as normal or no acute changes in 81% (n=266) of patients, and abnormal in 19% (n=64) of patients. The most common abnormal chest x-ray diagnoses were congestive heart failure (n=28; 8%) and pneumonia (n=17; 5%). Those with abnormal chest x-ray findings were significantly older (71 versus 55 years; p<0.001), had chest pain with shortness of breath (36% versus 11%; p<0.001), had significant past medical history (39% versus 14%; p<0.001), and were also tachypnoic (31% versus 12%; p<0.001). CONCLUSION: This study found that patients with non-traumatic chest pain are likely to have a normal chest x-ray if they were young, not tachypnoeic or short of breath, and had no significant past medical history. A larger study is required to confirm these findings. PMID- 22303505 TI - HLA Antigens in Omani Psoriasis Vulgaris Patients. AB - OBJECTIVES: To determine the frequency of different HLA-antigens in patients with plaque psoriasis in the Omani Arab population. METHODS: Fifty four Omani patients clinically diagnosed with plaque psoriasis attending the dermatology outpatient clinic in Al-Nahdah Hospital (the tertiary dermatology centre in Oman) were selected for HLA studies. RESULTS: HLA-B52 was present in 20.4% of patients 11/54 and in 5% of controls without psoriasis 5/100. For the association p was <0.004 and the relative risk (RR) was 4.86. CONCLUSION: Psoriasis does not appear to be associated universally with the same HLA antigens. The association of HLA-B52 with plaque psoriasis in Omani patients compares with the HLA-Cw6, -Bw57 and -DR7 preponderance in most other ethnic groups. PMID- 22303506 TI - Effect of 10% phenylephrine eye drops on systemic blood pressure in normotensive & hypertensive patient. AB - OBJECTIVES: A prospective study to evaluate the effect of 10% Phenylephrine eye drops on systemic blood pressure in normotensive and hypertensive patients. METHODS: The sample comprised of 55 normotensive patients and 34 hypertensive patients were subjected to 10% Phenylephrine eye drops during routine eye examination. RESULTS: No statistically and clinically significant increase in blood pressure after the instillation of 10% Phenylephrine eye drops was seen in 87% of normotensive patients and 76% of hypertensive patients. Mild rise of blood pressure was seen in 11% of normotensive patients and in 15% of the hypertensive patients. Only one patient (3%) had severe rise of blood pressure in the hypertensive group. CONCLUSION: This study shows that pupillary dilatation with 10% Phenylephrine eye drops did not significantly increase systemic blood pressure in normotensive and hypertensive patients. Although precautions should be taken when used in hypertensive patients. PMID- 22303507 TI - Kaposi sarcoma in calabar, southern Nigeria. AB - OBJECTIVES: There has been an increase in the prevalence of Kaposi sarcoma (KS) with the emergence of Human Immunodeficiency Virus (HIV). METHODS: Patients with histologic diagnosis of KS seen in the University of Calabar Teaching Hospital, Calabar between January 2007 and December 2008 were studied. Diagnosis of HIV was based on enzyme linked immunosorbent assay (ELISA). RESULTS: In total, 15 patients (10 males, 5 females, M: F=2:1) presented with KS and accounted for 33.0% of total skin malignancy and ranked second after squamous cell carcinoma, 42.0%. Their ages ranged from 5 and 60 years (mean 37.5 years). Twelve patients (M=8, F=4), 80%, were HIV seropositive, while 3 (M=2, F=1) were HIV seronegative. The lower limb was the commonest affected site, 57.9%. CONCLUSION: The most common clinical type was HIV related KS. Ignorance, sociocultural beliefs, poverty, late presentation were underlying issues. PMID- 22303508 TI - Prophylaxis for opportunistic infections for kidney transplantation recipients at the royal hospital in oman. AB - OBJECTIVES: The main objective of this study is to ensure all patients undergone kidney transplantation receives appropriate standard PCP prophylaxis soon after transplantation, unless contraindicated. METHODS: A prospective study included all kidney transplantation recipients from January 2008 to August 2008. A data collection sheet was designed and reviewed in focus group meetings and modified accordingly. The subjects were followed-up during the admission for transplantation to the date of discharge. The discharge prescriptions were screened to ensure all the kidney transplantation recipients were prescribed appropriate PCP prophylaxis before discharge. All prescriptions with NO PCP prophylaxis were intervened by the clinical pharmacist. The focus group meetings suggested designing a questionnaire using likerts scale. The purpose was to highlight doctors' perception towards PCP prophylaxis for renal transplant recipients. The questionnaires were distributed to all the nephrology doctors (consultants, senior specialists and medical officers). The data were entered in the data collection sheet and were analyzed by using simple statistical methods. RESULTS: Almost 80% of the prescriptions did not included (TMP/SMX) for PCP among which 20% of the prescriptions were for patients with G6PD deficiency. The clinical pharmacist's interventions resulted that all discharge prescriptions were modified and (TMP/SMX) was prescribed for patients who were legible for a PCP prophylaxis CONCLUSION: In the absence of prophylaxis, the incidence of PCP in solid organ transplant recipients ranges from 6.8% to 22%, necessitating PCP prophylaxis for at least 6 months following transplantation. Despite the widespread knowledge on PCP prophylaxis, most of the patients were discharged with no prophylactic treatment for PCP. After pharmacist's intervention the prescriptions were edited and PCP prophylaxis was added. PMID- 22303509 TI - Large Brunner's Gland Hamartoma: A Case Report. AB - Brunner's gland hamartoma is an extremely uncommon benign tumor of the duodenum. Most of the lesions are small, asymptomatic and are detected incidentally. It may rarely attain a large size and produces a variety of clinical manifestations. Imaging modalities and endoscopy may locate the lesion, but definitive diagnosis requires histopathological examination. We report a case of a 58-year-old Omani female who presented with obstruction due to a large Brunner's gland hamartoma. PMID- 22303510 TI - Successful revascularization of near total amputation of the upper limb at the sultan qaboos hospital, salalah. AB - Severe crush injuries to the upper limb may require a formal amputation with devastating consequences to the patient. We report a patient with a near total amputation at the level of mid-forearm who underwent revascularization and salvage of his hand. The operative details of this case are described. It is the first time that such a patient has been treated successfully by plastic surgeons and orthopedic surgeons at the Sultan Qaboos Hospital, Salalah. Awareness of the possibility of salvage should be spread among health care personnel as well as the need for immediate attention by a multispeciality team. Literature related to the operative technique, contraindications and long term results is reviewed. PMID- 22303511 TI - Metastatic squamous cell carcinoma of foot: case report. AB - Squamous cell carcinoma of the foot is rare. A case report of occurrence of metastatic squamous carcinoma of the foot with resemblance to verrucous type in an elderly female is presented. This metastatic lesion developed four years after excision of primary squamous cell carcinoma from the left thigh. The patient presented with a painful, exophytic, ulcerated mass on the foot of four months' duration. Fine-needle aspiration and edge biopsy documented this lesion as squamous cell carcinoma. PMID- 22303512 TI - Nasal Endotracheal Intubation under Fibreoptic Endoscopic Control in Difficult Oral Intubation, Two Pediatric Cases of Submandibular Abscess. AB - Securing an airway in children with trismus is challenging and dangerous. Sound clinical judgment is critical for timing and for selecting the method for airway intervention. We present two pediatric cases of submandibular abscess with difficult oral intubation who underwent incision and drainage. Large facial (jaw) swelling, trismus-limited mouth opening, edema, protruding teeth, and altered airway anatomy makes airway management more difficult. Chances of rupture of abscess intraorally and aspiration under General Anesthesia (GA) is a major threat. Loss of airway under muscle relaxation, difficult to ventilate, difficult to intubate and unwillingness for awake intubation in the pediatric age group makes these cases most challenging. On the basis of our experience, both cases were successfully intubated in anaesthetized, spontaneously breathing children with visual-guided fibreoptic intubation. PMID- 22303513 TI - Ultrasound Location of Misplaced Levonorgestrel Releasing Intrauterine System (LNG-IUS) - is it easy? AB - The Levonorgestrel intrauterine device (LNG-IUD) is a hormone-containing device licensed for treatment of menorrhagia and contraception. Though complications such as perforation have been reported similar to other non-hormonal intrauterine devices, the diagnosis of such complications is difficult with this device because the LNG-IUD has a different ultrasound appearance compared to copper devices and these case reports are intended to emphasize this point. PMID- 22303514 TI - A chronic granulomatous disease of childhood. PMID- 22303515 TI - Coordination Chemistry of Polyaromatic Thiosemicarbazones 2: Synthesis and Biological Activity of Zinc, Cobalt, and Copper Complexes of 1-(Naphthalene-2 yl)ethanone Thiosemicarbazone. AB - A novel thiosemicarbazone from 2-acetonaphthone (represented as acnTSC) has been synthesized and its basic coordination chemistry with zinc(II), cobalt(II), and copper(II) explored. The complexes were characterized by elemental analysis and various spectroscopic techniques and are best formulated as [M(acnTSC)(2)Cl(2)] with the metal likely in an octahedral environment. The anticancer activity of the complexes was determined against a panel of human colon cancer cells (HCT-116 and Caco-2). The compounds bind to DNA via an intercalative mode with binding constants of 9.7 * 10(4) M(-1), 1.8 * 10(5) M(-1), and 9.5 * 10(4) M(-1) for the zinc, cobalt, and copper complexes, respectively. PMID- 22303516 TI - Ovarian cancer spheroids use myosin-generated force to clear the mesothelium. AB - Dissemination of ovarian tumors involves the implantation of cancer spheroids into the mesothelial monolayer on the walls of peritoneal and pleural cavity organs. Biopsies of tumors attached to peritoneal organs show that mesothelial cells are not present under tumor masses. We have developed a live, image-based in vitro model in which interactions between tumor spheroids and mesothelial cells can be monitored in real time to provide spatial and temporal understanding of mesothelial clearance. Here we provide evidence that ovarian cancer spheroids utilize integrin- and talin- dependent activation of myosin and traction force to promote mesothelial cells displacement from underneath a tumor cell spheroid. These results suggest that ovarian tumor cell clusters gain access to the sub mesothelial environment by exerting force on the mesothelial cells lining target organs, driving migration and clearance of the mesothelial cells. PMID- 22303517 TI - The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force recommendations for the management of patients with mood disorders and comorbid conditions. PMID- 22303518 TI - Why are there no treatment guidelines for mood disorders and comorbidities? PMID- 22303519 TI - The CANMAT task force recommendations for the management of patients with mood disorders and comorbid anxiety disorders. AB - BACKGROUND: Comorbid mood and anxiety disorders are commonly seen in clinical practice. The goal of this article is to review the available literature on the epidemiologic, etiologic, clinical, and management aspects of this comorbidity and formulate a set of evidence- and consensus-based recommendations. This article is part of a set of Canadian Network for Mood and Anxiety Treatments (CANMAT) Comorbidity Task Force papers. METHODS: We conducted a PubMed search of all English-language articles published between January 1966 and November 2010. The search terms were bipolar disorder and major depressive disorder, cross referenced with anxiety disorders/symptoms, panic disorder, agoraphobia, generalized anxiety disorder, social phobia, obsessive-compulsive disorder, and posttraumatic stress disorder. Levels of evidence for specific interventions were assigned based on a priori determined criteria, and recommendations were developed by integrating the level of evidence and clinical opinion of the authors. RESULTS: Comorbid anxiety symptoms and disorders have a significant impact on the clinical presentation and treatment approach for patients with mood disorders. A set of recommendations are provided for the management of bipolar disorder (BD) with comorbid anxiety and major depressive disorder (MDD) with comorbid anxiety with a focus on comorbid posttraumatic stress disorder, use of cognitive-behavioral therapy across mood and anxiety disorders, and youth with mood and anxiety disorders. CONCLUSIONS: Careful attention should be given to correctly identifying anxiety comorbidities in patients with BD or MDD. Consideration of evidence- or consensus-based treatment recommendations for the management of both mood and anxiety symptoms is warranted. PMID- 22303520 TI - The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force recommendations for the management of patients with mood disorders and comorbid attention-deficit/hyperactivity disorder. AB - BACKGROUND: Patients with bipolar disorder (BD) and major depressive disorder (MDD) experience adult attention-deficit/hyperactivity disorder (ADHD) at rates substantially greater than the general population. Nonetheless, ADHD frequently goes untreated in this population. METHODS: We reviewed the literature regarding the management of adult ADHD in patients with mood disorders. Because a limited number of studies have been conducted in adults, our treatment recommendations also are partly informed by research in children and adolescents with BD+ADHD or MDD+ADHD, adults with ADHD, and our clinical experience. RESULTS: In individuals with mood disorders, ADHD is best diagnosed when typical symptoms persist during periods of sustained euthymia. Individuals with BD+ADHD, particularly those with bipolar I disorder (BD I), are at risk for mood destabilization with many ADHD treatments, and should be prescribed mood-stabilizing medications before initiating ADHD therapies. Bupropion is a reasonable first-line treatment for BD+ADHD, while mixed amphetamine salts and methylphenidate also may be considered in patients determined to be at low risk for manic switch. Modafinil and cognitive-behavioral therapy (CBT) are second-line choices. In patients with MDD+ADHD and moderate to severe depression, MDD should be the treatment priority, whereas in mildly depressed or euthymic patients the order may be reversed. First line treatments for MDD+ADHD include bupropion, an antidepressant plus a long acting stimulant, or an antidepressant plus CBT. Desipramine, nortriptyline, and venlafaxine are second-line options. CONCLUSIONS: Clinicians should be vigilant in screening for comorbid ADHD in mood disorder patients. ADHD symptoms can respond to appropriately chosen treatments. PMID- 22303521 TI - The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force recommendations for the management of patients with mood disorders and comorbid substance use disorders. AB - BACKGROUND: Mood disorders, especially bipolar disorder (BD), frequently are associated with substance use disorders (SUDs). There are well-designed trials for the treatment of SUDs in the absence of a comorbid condition. However, one cannot generalize these study results to individuals with comorbid mood disorders, because therapeutic efficacy and/or safety and tolerability profiles may differ with the presence of the comorbid disorder. Therefore, a review of the available evidence is needed to provide guidance to clinicians facing the challenges of treating patients with comorbid mood disorders and SUDs. METHODS: We reviewed the literature published between January 1966 and November 2010 by using the following search strategies on PubMed. Search terms were bipolar disorder or depressive disorder, major (to exclude depression, postpartum; dysthymic disorder; cyclothymic disorder; and seasonal affective disorder) cross referenced with alcohol or drug or substance and abuse or dependence or disorder. When possible, a level of evidence was determined for each treatment using the framework of previous Canadian Network for Mood and Anxiety Treatments recommendations. The lack of evidence-based literature limited the authors' ability to generate treatment recommendations that were strictly evidence based, and as such, recommendations were often based on the authors' opinion. RESULTS: Even though a large number of treatments were investigated for alcohol use disorder (AUD), none have been sufficiently studied to justify the attribution of level 1 evidence in comorbid AUD with major depressive disorder (MDD) or BD. The available data allows us to generate first-choice recommendations for AUD comorbid with MDD and only third-choice recommendations for cocaine, heroin, and opiate SUD comorbid with MDD. No recommendations were possible for cannabis, amphetamines, methamphetamines, or polysubstance SUD comorbid with MDD. First choice recommendations were possible for alcohol, cannabis, and cocaine SUD comorbid with BD and only second-choice recommendations for heroin, amphetamine, methamphetamine, and polysubstance SUD comorbid with BD. No recommendations were possible for opiate SUD comorbid with BD. Finally, psychotherapies certainly are considered an essential component of the overall treatment of SUDs comorbid with mood disorders. However, further well-designed studies are needed in order to properly assess their potential role in specific SUDs comorbid with a mood disorder. CONCLUSIONS: Although certain treatments show promise in the management of mood disorders comorbid with SUDs, additional well-designed studies are needed to properly assess their potential role in specific SUDs comorbid with a mood disorder. PMID- 22303522 TI - The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force recommendations for the management of patients with mood disorders and comorbid personality disorders. AB - BACKGROUND: The association between mood disorders and personality disorders (PDs) is complicated clinically, conceptually, and neurobiologically. There is a need for recommendations to assist clinicians in treating these frequently encountered patients. METHODS: The literature was reviewed with the purpose of identifying clinically relevant themes. MedLine searches were supplemented with manual review of the references in relevant papers. From the extant evidence, consensus-based recommendations for clinical practice were developed. RESULTS: Key issues were identified with regards to the overlap of PDs and mood disorders, including whether certain personality features predispose to mood disorders, whether PDs can reliably be recognized if there is an Axis I disorder present, whether personality disturbances arise as a consequence or are a forme fruste of mood disorders, and whether personality traits or disorders modify treatment responsiveness and outcome of mood disorders. CONCLUSION: This paper describes consensus-based clinical recommendations that arise from a consideration of how signals from the literature can impact clinical practice in the treatment of patients with comorbid mood and personality pathology. Additional treatment studies of patients with the comorbid conditions are required to further inform clinical practice. PMID- 22303523 TI - The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force recommendations for the management of patients with mood disorders and comorbid metabolic disorders. AB - BACKGROUND: One goal of the Canadian Network for Mood and Anxiety Treatments (CANMAT) is to develop evidence-based and best practice educational programs and recommendations. Our group conducted a comprehensive literature review to provide evidence-based recommendations for treating metabolic comorbidity in individuals with major depressive disorder (MDD) and bipolar disorder (BD). METHODS: We searched PubMed for all English-language articles published January 1966 to November 2010 using BD and MDD cross-referenced with metabolic syndrome, obesity, diabetes mellitus, hypertension, and dyslipidemia. That search was augmented by a review of articles reporting outcomes of an intervention targeting components of metabolic syndrome in individuals with MDD or BD. RESULTS: Consensus exists for the recommendation that individuals with MDD and BD should be routinely screened for risk factors that increase risk for metabolic syndrome. For excess weight, the best-studied pharmacologic approaches are metformin and topiramate, with emerging evidence for liraglutide and modafinil. For binge eating disorder, the best evidence in mood disorders was for cognitive-behavioral therapy as well as topiramate, zonisamide, and in select cases selective serotonin reuptake inhibitors. For dysglycemia, dyslipidemia, and hypertension, evidence supports cognitive-behavioral interventions and anti-diabetic, antilipidemic, and antihypertensive treatments. CONCLUSIONS: Comprehensive care of individuals with mood disorders should include routine evaluation of the risk and presence of metabolic syndrome and its components. Systematic evaluation of preventative and targeted treatments of metabolic syndrome in mood disorder populations is insufficient. PMID- 22303524 TI - The CANMAT task force recommendations for the management of patients with mood disorders and comorbid medical conditions: diagnostic, assessment, and treatment principles. AB - BACKGROUND: Medical comorbidity is commonly encountered in individuals with major depressive disorder (MDD) and bipolar disorder (BD). The presence of medical comorbidity has diagnostic, prognostic, treatment, and etiologic implications underscoring the importance of timely detection and treatment. METHODS: A selective review of relevant articles and reviews published in English-language databases (1968 to April 2011) was conducted. Studies describing epidemiology, temporality of onset, treatment implications, and prognosis were selected for review. RESULTS: A growing body of evidence from epidemiologic, clinical, and biologic studies suggests that the relationship between medical illness and mood disorder is bidirectional in nature. It provides support for the multiplay of shared and specific etiologic factors interlinking these conditions. CONCLUSIONS: This article describes the complex interactions between medical illness and mood disorders and provides a meaningful approach to their comorbid clinical diagnosis and management. PMID- 22303525 TI - The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force recommendations for the management of patients with mood disorders and select comorbid medical conditions. AB - BACKGROUND: Medical comorbidity in patients with mood disorders has become an increasingly important clinical and global public health issue. Several specific medical conditions are associated with an increased risk of mood disorders, and conversely, mood disorders are associated with increased morbidity and mortality in patients with specific medical disorders. METHODS: To help understand the bidirectional relationship and to provide an evidence-based framework to guide the treatment of mood disorders that are comorbid with medical illness, we have reviewed relevant articles and reviews published in English-language databases (to April 2011) on the links between mood disorders and several common medical conditions, evaluating the efficacy and safety of pharmacologic and psychosocial treatments. The medical disorders most commonly encountered in adult populations (ie, cardiovascular disease, cerebrovascular disease, cancer, human immunodeficiency virus, hepatitis C virus, migraine, multiple sclerosis, epilepsy, and osteoporosis) were chosen as the focus of this review. RESULTS: Emerging evidence suggests that depression comorbid with several medical disorders is treatable and failure to treat depression in medically ill patients may have a negative effect on medical outcomes. CONCLUSIONS: This review summarizes the available evidence and provides treatment recommendations for the management of comorbid depression in medically ill patients. PMID- 22303526 TI - Some historical remarks on microcrystalline arthritis (gout and chondrocalcinosis). AB - The history of microcrystalline arthritis only began in 1961 when Daniel McCarty and Joseph Lee Hollander demonstrated the presence of sodium monourate crystals in the synovial fluid of gouty patients. However, gout is a historical disease, thanks to the descriptions of Hippocrates, Caelius Aurelianus, Soranus of Ephesus and Araeteus of Cappadocia. The relationship between hyperuricemia and gout was first documented in the nineteenth century by Alfred Baring Garrod, who demonstrated deposits of uric acid crystals on a linen thread held dipped in acidified blood (the so-called "thread method"). Gout has always been considered a prerogative of the moneyed classes (arthritis divitum), and history is full of famous gouty personalities, including kings, emperors, popes, commanders, politicians, artists, writers, philosophers and scientists. Another form of microcrystalline arthritis, chondrocalcinosis, was identified as being a rheumatic disorder different from gout in the 1960s. As a specific clinical entity, it was first identified in 1958 by Dusan Zitnan and Stefan Sit'aj in a few Slovak families. PMID- 22303527 TI - Epidemiology of gout and chondrocalcinosis. AB - Gout is the most common cause of inflammatory arthritis affecting at least 1% of the population in industrialized countries. It is closely associated with hyperuricemia and is characterized by formation and reversible deposition of monosodium urate crystals in joints and extra-articular tissues. Several studies suggest that the prevalence and incidence of gout are rising. Numerous risk factors may in part explain this increasing trend including dietary and lifestyle changes, genetic factors, diuretic use and comorbid conditions such as hypertension, diabetes, cardiovascular disease, chronic renal disease and the metabolic syndrome. Chondrocalcinosis is characterized by the deposition of calcium pyrophosphate crystals in articular tissues, most commonly fibrocartilage and hyaline cartilage. Sporadic chondrocalcinosis is a common condition in the elderly and frequently associates with osteoarthritis. Hereditary haemochromatosis, hyperparathyroidism and hypomagnesaemia are metabolic disorders that predispose to secondary chondrocalcinosis.The prevalence of chondrocalcinosis is still rather uncertain and varies depending on the diagnostic criterion used in different studies. PMID- 22303528 TI - Metabolism of crystals within the joint. AB - Monosodium urate (MSU), calcium pyrophosphate dihydrate (CPPD) and basic calcium phosphate (BCP) crystals deposit in joints and surrounding tissues causing acute inflammation and chronic cartilage damage. A number of endogenous substances and physicochemical conditions affect their precipitation, growth and even dissolution, regulating their metabolism and inflammatory activity. We review how MSU and calcium crystals form within the joints and the various factor which regulate their formation. PMID- 22303529 TI - The mechanisms of inflammation in gout and pseudogout (CPP-induced arthritis). AB - Recent advances have stimulated new interest in the area of crystal arthritis, as microcrystals can be considered to be endogenous "danger signals" and are potent stimulators of immune as well as non-immune cells. The best known microcrystals include urate (MSU), and calcium pyrophosphate (CPP) crystals, associated with gout and pseudogout, respectively. Acute inflammation is the hallmark of the acute tissue reaction to crystals in both gout and pseudogout. The mechanisms leading to joint inflammation in these diseases involve first crystal formation and subsequent coating with serum proteins. Crystals can then interact with plasma cell membrane, either directly or via membrane receptors, leading to NLRP3 activation, proteolytic cleavage and maturation of pro-interleukin-1beta (pro IL1beta) and secretion of mature IL1beta. Once released, this cytokine orchestrates a series of events leading to endothelial cell activation and neutrophil recruitment. Ultimately, gout resolution involves several mechanisms including monocyte differentiation into macrophage, clearance of apoptotic neutrophils by macrophages, production of Transforming Growth Factor (TGF-beta) and modification of protein coating on the crystal surface. This review will examine these different steps. PMID- 22303530 TI - Clinical features of gout. AB - Gout is a metabolic disease characterized by hyperuricemia and the deposition of monosodium urate (MSU) crystals in the joints and soft tissues, consisting of a self-limited acute phase characterized by recurrent attacks of synovitis and a chronic phase in which inflammatory and structural changes of the joints and periarticular tissues may lead to persistent symptoms. Acute gout is characterized by a sudden monoarthritis of rapid onset, with intense pain, mostly affecting the big toe (50% of initial attacks), the foot, ankle, midtarsal, knee, wrist, finger, and elbow. Acute flares also occur in periarticular structures, including bursae and tendons. The presence of characteristic MSU crystals in the joint fluid, appearing needle-like and showing strong negative birefringence by polarized microscopy, is pivotal to confirm the diagnosis of gout. The time interval separating the first attack from subsequent episodes of acute synovitis may be widely variable, ranging from a few days to several years. During the period between acute attacks the patient is asymptomatic even if MSU deposition may continue to increase silently. The factors that control the rate, location, and degree of ongoing deposition in gouty patients are not well defined. Chronic gout is the natural evolution of untreated hyperuricemia in patients with gouty attacks followed by pain-free intercritical periods. It is characterized by the deposition of solid MSU crystal aggregates in a variety of tissues including joints, bursae and tendons. Tophi can occur in a variety of locations including the helix of the ear, olecranon bursa, and over the interphalangeal joints. Their development is usually related with both the degree and the duration of hyperuricemia. About 20% of patients with gout have urinary tract stones and can develop an interstitial urate nephropathy. There is a strong association between hyperuricaemia and the metabolic syndrome (the constellation of insulin resistance, hypertension, obesity and dyslipidaemia), and gouty patients often have a medical history of kidney disease, diabetes mellitus and signs of vascular illness such as coronary artery disease, heart failure and stroke, resulting with a poor overall quality of life. PMID- 22303531 TI - Calcium pyrophosphate deposition disease: clinical manifestations. AB - Calcium pyrophosphate deposition (CPPD) disease is an arthropathy caused by calcium pyrophosphate dihydrate (CPP) crystal deposits in articular tissues, most commonly fibrocartilage and hyaline cartilage. According to EULAR, four different clinical presentations can be observed: 1) asymptomatic CPPD; 2) osteoarthritis (OA) with CPPD; 3) acute CPP crystal arthritis; 4) chronic CPP inflammatory crystal arthritis. Acute CPP crystal arthritis is characterized by sudden onset of pain, swelling and tenderness with overlying erythema, usually in a large joint, most often the knee, wrist, shoulder, and hip. Occasionally, ligaments, tendons, bursae, bone and the spine can be involved. CPPD of the atlanto occipital joint (crowned dens syndrome) can cause periodic acute cervico occipital pain with fever, neck stiffness and laboratory inflammatory syndrome. Chronic inflammatory arthritis is characterized by joint swelling, morning stiffness, pain, and high ESR and CRP. The relationship between OA and CPPD is still unclear. The main problem is whether such crystals are directly involved in the pathogenesis of OA or if they are the result of joint degeneration. Diagnosis is based on evaluation of history and clinical features, conventional radiology, and synovial fluid examination. Non-polarized light microscopy should be used initially to screen for CPPD crystals based upon their characteristic morphology, and compensated polarized light microscopy, showing the crystals to be weakly positive birefringent, is recommended for definitive identification, although this last pattern only occurs in about 20% of samples. The main goals of CPPD therapy are control of the acute or chronic inflammatory reaction and prevention of further episodes. PMID- 22303532 TI - Cardiovascular and renal effects of hyperuricaemia and gout. AB - A number of epidemiological studies have reported an association between serum uric acid levels and a wide variety of high-risk conditions including hypertension, insulin resistance, and kidney and cerebro-cardiovascular disease. All things considered, serum uric acid may induce cardiovascular and kidney events both directly and indirectly by promoting other well-known mechanisms of damage. While asymptomatic hyperuricemia is currently not considered to be an indication for urate lowering therapy, there is growing evidence indicating a linear relationship between pharmacological reduction in serum uric acid and incidence of cardiovascular and renal events. PMID- 22303533 TI - Imaging studies of crystalline arthritides. AB - Gout, calcium pyrophosphate dihydrate (CPPD) deposition disease, and calcium hydroxyapatite deposition disease (HADD) are the three most common crystal induced arthropathies. Multimodality imaging may help in their diagnosis, and is useful for a precise and comprehensive assessment and grading of the related osteoarticular damage. Plain film radiography, due to its low cost and wide availability, is the first imaging technique to be used in crystal deposition diseases, providing well-known and specific findings for CPPD deposition disease and HADD, while it may undergrade the early osteoarticular lesions in gouty patients. Ultrasonography (US) is a radiation-free approach that accurately depicts crystal deposits in cartilage, peri- and intra-articular soft tissues, but it does not give a panoramic view of the affected joints. Cross-sectional imaging techniques can examine crystal deposits in the spine and axial joints. CT has the potential to distinguish monosodium urate (MSU) crystals from calcium containing crystals, due to their different attenuation values. MRI may demonstrate synovitis, erosions and bone marrow edema in gouty patients and it may differentiate tophi from other soft tissue nodules due to its high contrast resolution and power of tissue characterization. PMID- 22303534 TI - Treatment of hyperuricemia, gout and other crystalline arthritidies. AB - Gout is a very common joint disease which is due to chronic hyperuricemia and its related articular involvements. Yet it can be cured when appropriately managed. Comprehensive management of gout involves correct identification and addressing all causes of hyperuricemia, treating and preventing attacks of gouty inflammation (using colchicine NSAIDs, and/or steroids), and lowering serum urate (SUA) to an appropriate target level indefinitely. The ideal SUA target is, at a minimum, less than 6 mg/dL (60 mg/L or 360 MUmol/L), or even less than 5 mg/dL in patients with tophi. The SUA target should remain at less than 6 mg/dL for long in all gout patients, especially until tophi have resolved. Patient education and adherence to therapy are key point to the optimal management of gout, aspects which are often neglected. Adherence can be monitored in part by continuing, regular assessment of the SUA level. More difficult cases of gout often need a combination of urate lowering therapy (ULT) for both refractory hyperuricemia and chronic tophaceous arthritis. Chronic tophaceous gouty arthropathy which do not respond adequately to optimized oral ULT might benefit from the use of pegloticase, when this is available in, for example, Italy and other European countries. By contrast, in calcium pyrophosphate (CPP) crystal deposition disease (CPPD), as evidenced by pseudo gout attacks or chronic polyarthritis, similar anti-inflammatory strategies have been recommended, but there have as yet been no controlled trials. Of note, there is no treatment for the underlying metabolic disorders able to control the CPPD. Management of crystal-induced arthropathies (CIA) depends not only on clinical expression, namely acute attacks or chronic arthropathy, but also on the underlying metabolic disorder. We will mainly focus on gout as an archetype of CIA. PMID- 22303535 TI - Religion and attitudes toward abortion and abortion policy in Brazil. AB - This study examines the association between religion and attitudes toward the practice of abortion and abortion policy in Brazil. Drawing upon data from the 2002 Brazilian Social Research Survey (BSRS), we test a number of hypotheses with regard to the role of religion on opposition to the practice of abortion and its legalization. Findings indicate that frequently attending Pentecostals demonstrate the strongest opposition to the practice of abortion and both frequently attending Pentecostals and Catholics demonstrate the strongest opposition to its legalization. Additional religious factors, such as a commitment to biblical literalism, were also found to be significantly associated with opposition to both abortion issues. Ultimately, the findings have implications for the future of public policy on abortion and other contentious social issues in Brazil. PMID- 22303537 TI - Hands on stamps: Iran--medical subjects. PMID- 22303538 TI - In memoriam. PMID- 22303539 TI - Nutrition in Clinical Management of HIV-Infected Adolescents (>14 y old) and Adults including Pregnant and Lactating Women: What Do We Know, What Can We Do, and Where Do We Go from Here? Proceedings of a conference held in Washington, DC, July 26-28, 2010, Washington, DC. PMID- 22303540 TI - Proceedings of the 2010 IEEE Conference on Bioinformatics and Biomedicine, December 18-21, 2010, Hong Kong. PMID- 22303541 TI - Re: Evaluation of root resorption following rapid maxillary expansion using cone beam computed tomography. Angle Orthod. 2011 Aug 15. [Epub ahead of print]. DOI: 10.2319/060411-367.1 By Asli Baysal, Irfan Karadede, Seyit Hekimoglu, Faruk Ucar, Torun Ozer, Ilknur Veli, Tancan Uysal. PMID- 22303542 TI - In Memoriam: John Waterlow, CMG, FRS,FRCP, DSc. PMID- 22303543 TI - Re: A retrospective randomized double-blind comparison study of the effectiveness of Hawley versus vacuum-formed retainers. Angle Orthod. 2011;81: 404-409. By Stephen Barlin, Roland Smith, Ray Reed, Jonathan Sandy, Anthony John Ireland. PMID- 22303544 TI - Chronic disease prevention, asbestos exposure in diamond miners. PMID- 22303546 TI - And the winners are... CMS gives groups $20,000 to test innovations. PMID- 22303545 TI - Sincerest form of flattery. AB - As the CMS pushes for accountable care organizations, a number of states are adding ACO-like features to their Medicaid programs. Many see those changes as likely to boost quality while saving money. "The ability to appropriately manage and provide the services that those low-income patients need in a way that is cost-effective is the most important way to maintain access to care for all," says Kate Walsh, of Boston Medical Center. PMID- 22303547 TI - D.C. dilemmas. PMID- 22303548 TI - Best performing U.S. healthcare stocks in 2011: ranked by total stock return through Dec. 31. PMID- 22303549 TI - Largest rehabilitation providers: ranked by number of free-standing and hospital based rehabilitation facilities, 2010. PMID- 22303550 TI - What's new in androgenetic alopecia: approvals, long-term safety data, cancer risk and treatment options for women. PMID- 22303551 TI - Re. Inflammation in rosacea and acne: implications for patient care. PMID- 22303552 TI - The new face of fillers: integrating evidence, experience and a little imagination at the next frontier. PMID- 22303554 TI - Russian, US vets collaborate on distemper threat to tigers. PMID- 22303553 TI - Researchers say fungus causes deadly bat disease. PMID- 22303555 TI - Mystery illness killing Arctic ringed seals may be spreading. PMID- 22303556 TI - Researchers: how porphyromonas gingivalis contributes to periodontal disease identified. PMID- 22303557 TI - Bacteria found in saliva linked to pancreatic cancer, study shows. PMID- 22303558 TI - Factors associated with chronic TMD identified, researchers report. PMID- 22303559 TI - ["Broad spectrum psychotherapy": from treatment of physically ill patients to guideline psychotherapy]. PMID- 22303560 TI - A colonial female economy: Sydney, Australia. PMID- 22303561 TI - Exploding England: the dialectics of mobility and settlement in early modern England. PMID- 22303563 TI - The everyday lives of Parisian women and the October days of 1789. PMID- 22303564 TI - The sad story of George Hall: adultery, murder and the politics of mercy in mid Victorian England. PMID- 22303565 TI - [Concerning the territorial dependence of migratory trends between Slovakia and the Czech lands after World War II]. PMID- 22303566 TI - ["Give us the potatoes or there'll be a revolution": hunger riots, strikes, and mass protests in Bohemia, 1914-18]. PMID- 22303567 TI - [Study on ion channel transporters as a target for the drug discovery]. PMID- 22303568 TI - Food fortification. PMID- 22303569 TI - Efficacy of multi-micronutrient fortified biscuits on urinary iodine levels of adolescent girls from Jaipur, India. AB - INTRODUCTION: Iodine deficiency disorders are a public health problem in India. The aim of the study was to examine the effect of multi-micronutrient-fortified biscuits on urinary iodine levels of adolescent girls (n = 51, 10-16 years) studying in a government school in Jaipur city, India. METHODS: The study was designed as an intervention study. Biscuits fortified with 150 mcg iodine, 30 mg iron, 100 mcg folic acid, 600 mcg vitamin A and 40 mg vitamin C were provided daily to the subjects on all working days over a 4-month period. The iodine status of the adolescent girls was determined through urinary iodine levels. RESULTS: Supplementation with biscuits resulted in a significant increase in the mean urinary iodine level from 118.2 to 157.2 mcg/l and in the median value from 121 to 149 mcg/l. Prior to the intervention, 21.6% of the subjects had mild iodine deficiency but at the end of the intervention period, all the girls were iodine sufficient. Hence, iodine supplementation using biscuits resulted in improved iodine status of Indian adolescent girls. CONCLUSION: It is, therefore, recommended that the school system be used for micronutrient supplementation interventions to improve the nutritional status of children and adolescents as there is more regimentation in a school setting for distribution of nutrient fortified food products to students. PMID- 22303570 TI - Familial and socio-environmental predictors of overweight and obesity among primary school children in Selangor and Kuala Lumpur. AB - INTRODUCTION: A cross-sectional study was conducted to determine the familial and socio-environmental predictors of overweight and obesity among 1430, 9-12 year old primary school children and their parents in Selangor and Kuala Lumpur. METHODOLOGY: Body weight and height were measured and body mass index was calculated. Modified Child Feeding (CFQ) and Determinants of Adolescent Social Well-being and Health (DASH) questionnaires were used to measure familial and socio-environmental factors. RESULTS: A total of 17.9% of the children were overweight while 16.0% were obese. Positive relationships were found between child's BMI and parent's BMI (r = 0.129, p < or = 0.01), concern about child's weight (r = 0.125, p < or = 0.01) and restriction (r = 0.057, p < or = 0.05) to unhealthy foods. However, negative relationships were found between child's BMI with pressure to eat (r = -0.135, p < or = 0.01) and neighbourhood safety perception (r = -0.053, p < or = 0.05). The logistic regression analysis showed that being male (Exp (beta) = 0.538; 95% CI = 0.421-0.687), higher parent's BMI (Exp (beta) = 1.055; 95% CI = 1.028-1.082), higher concern about child's weight (Exp (beta) = 1.082; 95% CI = 1.030-1.127), low pressure to eat (Exp (beta) = 0.857; 95% CI = 0.801-0.916) and low perception of neighbourhood safety (Exp (beta) = 0.951; 95% CI = 0.913-0.990) were significantly associated with increased risk of overweight. CONCLUSION: Parents should be the main target for education to modify children's weight status. Further research should be carried out to understand the mechanism of influence of parents and the socio-environment on child's health. PMID- 22303571 TI - Influence of food intake and eating habits on hypertension control among outpatients at a government health clinic in the Klang Valley, Malaysia. AB - INTRODUCTION: In Malaysia, hypertension prevalence has increased from 13% in 1996 to 43% in 2006 based on the Third National Health and Morbidity Survey. METHODOLOGY: Recognising the importance of hypertension control to prevent cardiovascular morbidity and mortality, a cross-sectional study was carried out to assess factors influencing blood pressure among 74 hypertensive adults (22 men, 52 women, mean age 61.1 +/- 8.8 years old) attending an outpatient clinic of a government health clinic in Klang Valley. Subjects were interviewed to obtain information on social and health, physical activity level and food intake using Diet History Questionnaire (DHQ) and Food Frequency Questionnaire (FFQ). Anthropometric measurements including weight, height, waist circumference and percentage of body fat were also conducted. RESULTS: The majority of the subjects (71.6%) had poor hypertension control as determined using blood pressure. Women aged 30-59 years old had a higher mean diastolic blood pressure (87.3 +/- 11.6 mmHg) than women aged 60 years old (78.5 +/- 9.5 mmHg) (p < 0.05). Most of the men (36.4%) achieved three out of six Medical Nutrition Therapy (MNT) for Hypertension Recommendations as outlined by the Malaysian Dietitians' Association. About one-third (30.8%) of the women achieved two out of six of the guidelines. High sodium intake (adjusted OR 3.501, 95% CI 1.116-10.985, p < 0.05), daily consumption of coffee (adjusted OR 0.302, 95% CI 0.093-0.983, p < 0.05) and less intake of milk (adjusted OR 3.328, 95% CI 1.055-10.493, p < 0.05) were associated with uncontrolled hypertension. CONCLUSION: Three quarters of the subjects had unsatisfactory hypertensive control and was related to food intake and eating habits including high salt diet, coffee consumption and inadequate milk intake were unsatisfactory. There is a need to implement a nutrition intervention programme based on MNT to achieve good hypertensive control among subjects. PMID- 22303572 TI - Determination of factors associated with physical activity levels among adolescents attending school in Kuantan, Malaysia. AB - INTRODUCTION: Findings from the National Health and Morbidity Survey III (MOH, 2008) indicate a 43.7% prevalence of physical inactivity among Malaysian adults. This sedentary lifestyle can also be observed among children and adolescents. METHODOLOGY: A cross-sectional study was conducted to determine factors associated with physical activity levels of four hundred, 13 year-old adolescents in Kuantan, Pahang. Data on socio-demographic, health-related, and psychosocial factors were collected using a self-administered questionnaire while physical activity level was assessed using the Physical Activity Questionnaire for Older Children (PAQ-C). RESULTS: About one-third of the respondents were in the low physical activity level category, 61.5% were in the moderate category and only 3.0% of the adolescents were in the high physical activity level category. Males were more physically active than females (chi2 = 23.667, p = 0.0001) with female adolescents (45.1%) twice as likely as male adolescents (22.1%) to be in the low physical activity level category. The associations between physical activity level with socio-demographic and health-related factors, perception of weight status and body parts satisfaction were not significant. However, physical activity was found to be positively correlated with physical activity self efficacy (r = 0.496, p = 0.0001), peer influence ( r = 0.468, p = 0.0001), family influence (r = 0.298, p = 0.0001) and beliefs in physical activity outcomes (r = 0.207, p = 0.0001). Negative relationships were found between physical activity with depression (r = -0.116, p = 0.021) and body size discrepancy (r = -0.143, p < 0.01). Respoedbnts who had a better perception of their current health status were more physically active chi2 = 21.062, p = 0.0001). Multivariate analyses for the prediction of physical activity showed that physical activity self-efficacy, sex and peer influence were the most significant contributors in explaining physical activity among adolescents. CONCLUSION: Physical activity interventions should include psychosocial components as mediator variables in interventions designed to promote regular physical activity in adolescence. PMID- 22303573 TI - Effect of gender and nutritional status on academic achievement and cognitive function among primary school children in a rural district in Malaysia. AB - INTRODUCTION: The aim of this study was to investigate the relationship between gender, birth weight, nutritional status, and iron status of children with their academic performance and cognitive function. METHODS: Two hundred and forty-nine children, seven to nine years of age, were recruited by systematic sampling from six primary schools in a rural area in Malaysia. Cognitive function was assessed by using Raven's Coloured Progressive Matrices (R-CPM). Academic performance of the children was recorded from their school final examination results in four subjects including Malay language, English, Mathematics, and Science. Birth weight was recorded from the birth certificate, and nutritional status was determined by weight-for-age z score and height-for-age z score. RESULTS: Girls had a significantly higher score in all the academic tests, but a lower cognitive score compared to boys. Nutritional status was found to be correlated significantly with academic performance. Academic and cognitive function scores were also found to be correlated significantly with birth weight, parents' education, and family income. In a multivariate analysis, gender remained the significant predictor of academic function, and iron status and haemoglobin were the significant predictors of cognitive function, after controlling for other variables. CONCLUSION: The study showed that girls performed better academically than boys in rural Malaysia. Nutritional status, parents' education and family income could be additional modifiable factors to improve academic performance of the children. More attention is needed to improve academic achievements of boys at their early school years. PMID- 22303574 TI - No association of peptide tyrosine-tyrosine (PYY) gene R72T variant with obesity in the Kampar Health Clinic cohort, Malaysia. AB - INTRODUCTION: Peptide Tyrosine-Tyrosine (PYY) is a 36-amino acid peptide hormone released post-prandially from the endocrine cells in the intestinal tract to suppress pancreatic secretions and eventually reduce appetite. The R72T variant in the PYY gene (rs1058046) has been associated with increased susceptibility to obesity. Therefore, the objective of this study was to investigate the association of this variant with obesity and its related anthropometric measurements among the Kampar Health Clinic cohort, Malaysia. METHODOLOGY: A total of 197 (78 males, 119 females; 98 non-obese, 99 obese) subjects were recruited by convenience sampling and anthropometric measurements were taken. Genotyping was performed using StuI Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP), revealing 61 RR, 94 RT and 42 TT subjects. RESULTS: Most of the obese subjects had the RT genotype (50.5%), while only 18.2% were TT. PYY R72T genotypes and alleles had no association with obesity (p = 0.535; 0.074, respectively), gender (p = 0.767; p = 0.100, respectively) but were associated with ethnicity (p = 0.003; p = 0.002, respectively). Among the 13 anthropometric measurements taken, significant difference was only found in Waist Circumference (WC) and Visceral Fat Level (VFL) among the alleles, suggesting that subjects with T allele will have an increment of 1.82 cm in WC and 1.32% in VFL. CONCLUSION: The R72T variant in PYY gene was not associated with obesity and most of its related anthropometric measurements. This suggests that other genes and/or environmental factors like dietary habits and lifestyle factors may be the contributors of obesity. PMID- 22303575 TI - Differences in eating behaviours, dietary intake and body weight status between male and female Malaysian University students. AB - INTRODUCTION: University students are potentially important targets for the promotion of healthy lifestyles as this may reduce the risks of lifestyle-related disorders later in life. This cross-sectional study examined differences in eating behaviours, dietary intake, weight status, and body composition between male and female university students. METHODOLOGY: A total of 584 students (59.4% females and 40.6% males) aged 20.6 +/- 1.4 years from four Malaysian universities in the Klang Valley participated in this study. Participants completed the Eating Behaviours Questionnaire and two-day 24-hour dietary recall. Body weight, height, waist circumference and percentage of body fat were measured. RESULTS: About 14.3% of males and 22.4% of females were underweight, while 14.0% of males and 12.3% of females were overweight and obese. A majority of the participants (73.8% males and 74.6% females) skipped at least one meal daily in the past seven days. Breakfast was the most frequently skipped meal. Both males and females frequently snacked during morning tea time. Fruits and biscuits were the most frequently consumed snack items. More than half of the participants did not meet the Malaysian Recommended Nutrient Intake (RNI) for energy, vitamin C, thiamine, riboflavin, niacin, iron (females only), and calcium. Significantly more males than females achieved the RNI levels for energy, protein and iron intakes. CONCLUSION: This study highlights the presence of unhealthy eating behaviours, inadequate nutrient intake, and a high prevalence of underweight among university students. Energy and nutrient intakes differed between the sexes. Therefore, promoting healthy eating among young adults is crucial to achieve a healthy nutritional status. PMID- 22303576 TI - The Malaysian Childhood Obesity Treatment Trial (MASCOT). AB - INTRODUCTION: The present study describes a randomised controlled trial (RCT) based on a novel, generalisable intervention for childhood obesity, comparing the intervention with a no-treatment control group. METHOD: The Malaysian Childhood Obesity Treatment Trial (MASCOT) was a single-blind RCT of a dietetic treatment for childhood obesity in children of primary school age (7 to 11 years old) in Kuala Lumpur, Malaysia. The MASCOT comprising eight sessions, of an 8-hour family centred group treatment programme is described, based on behavioural change techniques. The study sample was characterised by BMI z-score, health related quality of life reported by participants and their parents (PedsQL questionnaire), objectively measured habitual physical activity and sedentary behaviour (Actigraph accelerometry) RESULTS: The MASCOT sample of 107 children was characterised by a low quality of life, mean total score on PedsQL 67.7 (4.5) as reported by the children, and 66.0 (16.4) as reported by their parents. The children spent, on average, 89% of their waking day on sedentary activity, and 1% of the day in moderate-vigorous intensity physical activity, equivalent to only around 8 minutes/day. CONCLUSION: Obese children in the MASCOT study had an impaired quality of life, high levels of sedentary behaviour and very low levels of physical activity. PMID- 22303577 TI - Effects of fortified lysine on the amino acid profile and sensory qualities of deep-fried and dried noodles. AB - INTRODUCTION: Lysine fortification of wheat flour has been used toward reducing protein energy malnutrition in developing countries. METHODS: The feasibility of fortifying instant noodles with lysine was evaluated based on sensory qualities and the residual lysine content. Fifty grams of deep-fried and dried instant noodles were fortified with 0.23 and 0.21 g lysine, respectively. The production temperatures used for deep-frying were 165-175 degrees C and for drying, 80-105 degrees C; these are the temperatures used in the industrial production of both kinds of noodles. Lysine fortification was then performed at the local factories using the commercial production lines and packaging for both types of instant noodles. Both fortified and unfortified deep-fried and dried instant noodles were stored at 50 degrees C under fluorescent light for 2 and 4 months, respectively. RESULTS: The fortified products were tested for residual lysine content and sensory qualities as compared with unfortified noodles. The results show fortified products from the tested processing temperatures were all accepted. After storage, significant losses of lysine were not found in both types of noodles analysed. The lysine-fortified noodles had amino acid scores of 102% and 122%, respectively. After 2 months, the sensory quality of fortified deep-fried noodles was still acceptable; however, the dried noodles turned to an unacceptable dark colour. CONCLUSION: This study shows that it is feasible to fortify deep-fried instant noodles with lysine, though lysine fortification exhibited an undesirable colour in the dried instant noodles after storage. PMID- 22303578 TI - MTHFR C677T polymorphism, homocysteine and B-vitamins status in a sample of Chinese and Malay subjects in Universiti Putra Malaysia. AB - INTRODUCTION: Methylenetetrahydrofolate reductase (MTHFR) C677T is involved in folate and homocysteine metabolism. Disruption in the activity of this enzyme will alter their levels in the body. METHODOLOGY: This study assessed MTHFR C677T polymorphism and its relationship with serum homocysteine and B-vitamins levels in a sample of Chinese and Malays subjects in UPM, Serdang. One hundred subjects were randomly selected from among the university population. Folate, vitamin B12, B6, and homocysteine levels were determined using MBA, ECLIA, and HPLC, respectively. PCR coupled with HinfI digestion was used for detection of MTHFR C677T polymorphism. RESULTS: The frequency of T allele was higher in the Chinese subjects (0.40) compared to the Malay (0.14). Folate, vitamin B12 and B6 levels were highest in the wild genotype in both ethnic groups. Subjects with heterozygous and homozygous genotype showed the highest homocysteine levels. The serum folate and homocysteine were mainly affected by homozygous genotype. CONCLUSION: MTHFR C677T polymorphism plays an important role in influencing the folate and homocysteine metabolism. PMID- 22303579 TI - Chocolate: food for moods. AB - INTRODUCTION: Chocolate is a popular food and its consumption has long been associated with enjoyment and pleasure. The effect of chocolate on mood too has long been recognised. Chocolate is thought to have interactions with neurotransmitters which contribute to mood modulation and appetite regulation. However, the evidence in chocolate and mood studies remains highly controversial. As more is known about the influence of chocolate on mood, the reasons for these effects appear increasingly complex and inter-related. METHODS: We reviewed chocolate's properties and the principal hypotheses addressing its mood altering propensities. RESULTS: The relationship between chocolate and mood are highly complex, combining psychopharmacological components, nutritional and sensory characteristics of the food. Individual and situational differences on chocolate consumption may also exert influence on mood and the mixed results in previous research indicate that the direction of the association remains unclear. CONCLUSION: The association between chocolate consumption and emotions warrants further multi-prong investigations to substantiate chocolate's mood alterating propensity. PMID- 22303580 TI - Major inorganic elements in tap water samples in Peninsular Malaysia. AB - INTRODUCTION: Quality drinking water should be free from harmful levels of impurities such as heavy metals and other inorganic elements. METHODS: Samples of tap water collected from 24 locations in Peninsular Malaysia were determined for inorganic element content. Minerals and heavy metals were analysed by spectroscopy methods, while non-metal elements were analysed using test kits. RESULTS: Minerals and heavy metals determined were sodium, magnesium, potassium, calcium, chromium, manganese, iron, nickel, copper, zinc, arsenic, cadmium and lead while the non-metal elements were fluoride, chloride, nitrate and sulphate. Most of the inorganic elements found in the samples were below the maximum permitted levels recommended by inter-national drinking water standard limits, except for iron and manganese. Iron concentration of tap water from one of the locations was higher than the standard limit. CONCLUSION: In general, tap water from different parts of Peninsular Malaysia had low concentrations of heavy metals and inorganic elements. PMID- 22303581 TI - Immunogenicity of pressure inactivated Edwardsiella tarda bacterin to Anguilla japonica (Japanese eel). AB - Japanese eel Anguilla japonica were immunized with inactivated Edwardsiella tarda bacterin preparations (formalin-killed cells, FKC (0.4%), formalin with heat killed cells, FHKC (0.1% and 70 degreesC for 10 min), heat-killed cells, HKC (70 degrees C for 15 min), potassium chloride-killed cells, KKC (0.6%), tannic acid killed cells, TKC (0.9%), citric acid-killed cells, CAKC (0.9%), pressure-killed cells, PKC (600 psi for 5 min) and electric current-killed cells, ECKC (100 mA at 12 v DC for 5 sec) via intraperitoneal injection in order to develop adequate inactivating method. Immune parameters in the immunized eel were measured to compare responses to different bacterins. Generally, eel rose agglutinating antibody titer in the serum within 2 week and the maximum titer occurred at 6 weeks post immunization. Elevated and significantly higher titer was produced with the PKC of E. tarda than other bacterin preparations. An Enzyme Linked Immunosorbent Assay (ELISA), to determine specific anti-E. tarda antibody in the serum, also showed significantly higher antibody titer with PKC than the other antigen preparations. Bacteriostatic assay with serum and live E. tarda indicated significantly higher activity in the PKC-immunized fish. Immunization with PKC also showed the increased level ofphagocytosis. PKC-inactivated vaccine at an immunization dose of 10(6) cells/fish induced high protection against experimental infection. Coincident with higher immune parameters and protection in the fish immunized with the PKC bacterin strongly suggested that pressure killing is an effective inactivating method to develop an effective vaccine against edwardsiellosis. PMID- 22303582 TI - Cytotoxic effect of organotin(IV) benzylisopropyldithiocarbamate compounds on Chang liver cell and hepatocarcinoma HepG2 cell. AB - Cancer is one of the main causes of mortality and morbidity in world. New compounds are currently being synthesized to combat this disease. The organotins are gaining more attention as anti-cancer agents due to their potent cytotoxicity properties. In this study, a series of newly synthesized organotins namely dimethyltin (IV) (compound 1), dibutyltin (IV) (compound 2) and triphenyltin (IV) benzylisopropyldithiocarbamate (compound 3) were assessed for their cytotoxic activities against human Chang liver cells and hepatocarcinoma HepG2 cells. The cytotoxicity of these organotins in both cells upon 24 h treatment was assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Compound 2 and 3 exhibited potent cytotoxic activities towards both cells where the IC50 values were less then 10 microM. The IC50 value for compound 2 was 2.5 microM in Chang liver cells and 7.0 microM in HepG2 cells whereas compound 3 exhibited an IC50 value of 1.5 microM in Chang liver cells and 2.5 microM in HepG2 cells. Therefore, compound 2 and 3 were more toxic against human Chang liver cells as compared to hepatocarcinoma HepG2 cells. Interestingly, compound 1 did not have any IC50 value in both cells and hence can be classified as non toxic. In conclusion, organotin (IV) benzylisopropyldithiocarbamate with insertion of dibutyl and triphenyl functional group possess potent cytotoxicity properties. Structural modification of these compounds can be carried out in further studies to produce less or non toxic effects towards normal human cell. PMID- 22303583 TI - The effect of hydro alcoholic Nettle (Urtica dioica) extracts on insulin sensitivity and some inflammatory indicators in patients with type 2 diabetes: a randomized double-blind control trial. AB - Type 2 diabetes is a metabolic disorder that is strongly associated with cardiovascular risk. Inflammation is a potential risk factor for cardiovascular disease. In this study, hydro alcoholic extract of Nettle (Urtica dioica) on insulin sensitivity and some inflammatory indicators in type 2 diabetic patients were studied. A randomized double-blind clinical trial on 50 men and women with type 2 diabetes was done for 8 weeks. Patients were adjusted by age, sex and duration of diabetes, then randomly divided into two groups, an intervention and control group. They received, 100 mg kg-1nettle extract or placebo in three portions a day for 8 weeks. Interleukin 6 (IL-6), Tumor Necrosis Factor-alpha (TNF-alpha), High Sensitive C-Reactive protein (hs-CRP) and Fasting Insulin concentration were measured. Insulin Sensitivity was calculated, at the beginning and the end of the study. The data were analyzed by SPSS version 18, p<0.05 was considered significant for all variables. After 8 weeks, IL-6 and hs-CRP showed a significant decrease in the intervention group compared to the control group (p<0.05). The findings showed that the hydro alcoholic extract of nettle has decreasing effects on IL-6 and hs-CRP in patients with type 2 diabetes after eight weeks intervention. PMID- 22303584 TI - Study of nano-fiber cellulose production by Glucanacetobacter xylinum ATCC 10245. AB - Bacterial Celluloses (BC) are gaining importance in research and commerce due to numerous factors affecting the bacterial cellulose characteristics and application in different industries. The aim of the present study was to produce bacterial cellulose in different media using different cultivation vessels. Bacterial cellulose was produced by static cultivation of Glucanacetobacter xylinum ATCC 10245 in different culture media such as Brain Heart Agar, Luria Bertani Agar /Broth, Brain Heart Infusion, Hestrin-Schramm and medium no. 125. Cultivation of bacterium was conducted in various culture vessels with different surface area. The cellulose membrane was treated and purified with a 0.1 M NaOH solution at 90 degreesC for 30 min and dried by a freeze- drier at -40 degreesC to obtain BC. The prepared bacterial cellulose was characterized by scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy and X ray diffraction (XRD). The amount of produced BC was related directly to the surface area of culture vessels. PMID- 22303585 TI - Effects of fruit collection date on Phillyrea latifolia L. seed germination. AB - This study was conducted to determine the effects of date of fruit collection on the germination of Phillyrea latifolia L. Fruits were collected between September and December of 2007, in Egirdir, Turkey. It was found that the one thousand seed weight for the species seeds was 400 g, with significant differences among dates of fruit collection. The highest germination percentage of 58% was obtained from the seeds collected on the ground from previous years on the 1st of September 2007. The seeds from crown on the 1st of September 2007 had a germination percentage of 42%. Moreover, seeds from crown on the 1st of November and December 2007 and 15th of October and November 2007 did not germinate. In conclusion, P. latifolia seeds collected on the ground from previous years could be sown in early autumn to obtain a high germination rate. PMID- 22303586 TI - Estimating outcomes of astronauts with myocardial infarction in exploration class space missions. AB - INTRODUCTION: We estimate likelihood of presenting rhythms and survival to hospital discharge outcome after acute cardiac ischemia with arrhythmia and/or myocardial infarction (AMI) during long-duration space missions (LDSM) using selected terrestrial cohorts in medical literature. Medical scenarios were risk stratified by coronary artery calcium score (CAC) and Framingham risk factors (FRF). METHODS: AMI with and without sudden cardiac arrest (SCA) likelihoods and clinically significant rhythm scenarios and associated outcomes in "astronaut like" cohorts were derived from two prospective trials identified by an evidence based literature review. Results are presented using an event sequence diagram and event time line. The association of increasing CAC scores and FRF with AMI and SCA outcomes was calculated. RESULTS: Low AMI likelihoods are estimated in individuals with CAC scores of zero or < 100 and a low number of FRF. Survival rate to hospital discharge after out of hospital SCA in a large urban environment study was 5.2%. EMS-witnessed ventricular tachycardia and/or ventricular fibrillation survival rate of 37.5% represents < 1% of all urban out of hospital AMI, and these patients have a high proportion of known ischemic cardiovascular and pulmonary disease "disqualifying for spaceflight." DISCUSSION: Multiple factors may be expected to delay or defeat rapid access to "chain of survival" resources during LDSM, lowering survival rates below urban levels of 5.2%. Low CAC and FRF reflect lower risk for AMI events. Zero CAC was associated with the lowest risk of AMI after 3.5 yr of follow-up. Quantifiable incidence and outcome characterization suggests AMI in LDSM outcomes will be relatively independent of in-flight medical resources. PMID- 22303587 TI - Computational simulation of hematocrit effects on arterial gas embolism dynamics. AB - BACKGROUND: Recent computational investigations have shed light into the various hydrodynamic mechanisms at play during arterial gas embolism that may result in endothelial cell (EC) injury. Other recent studies have suggested that variations in hematocrit level may play an important role in determining the severity of neurological complications due to decompression sickness associated with gas embolism. METHODS: To develop a comprehensive picture, we computationally modeled the effect of hematocrit variations on the motion of a nearly occluding gas bubble in arterial blood vessels of various sizes. The computational methodology is based on an axisymmetric finite difference immersed boundary numerical method to precisely track the blood-bubble dynamics of the interface. Hematocrit variations are taken to be in the range of 0.2-0.6. The chosen blood vessel sizes correspond to small arteries and small and large arterioles in normal humans. RESULTS: Relevant hydrodynamic interactions between the gas bubble and EC-lined vessel lumen have been characterized and quantified as a function of hematocrit levels. In particular, the variations in shear stress, spatial and temporal shear stress gradients, and the gap between bubble and vascular endothelium surfaces that contribute to EC injury have been computed. DISCUSSION: The results suggest that in small arteries, the deleterious hydrodynamic effects of the gas embolism on an EC-lined cell wall are significantly amplified as the hematocrit levels increase. However, such pronounced variations with hematocrit levels are not observed in the arterioles. PMID- 22303588 TI - Squat exercise biomechanics during short-radius centrifugation. AB - INTRODUCTION: Centrifuge-induced artificial gravity (AG) with exercise is a promising comprehensive countermeasure against the physiological de-conditioning that results from exposure to weightlessness. However, body movements onboard a rotating centrifuge are affected by both the gravity gradient and Coriolis accelerations. The effect of centrifugation on squat exercise biomechanics was investigated, and differences between AG and upright squat biomechanics were quantified. METHODS: There were 28 subjects (16 male) who participated in two separate experiments. Knee position, foot reaction forces, and motion sickness were recorded during the squats in a 1-G field while standing upright and while supine on a horizontally rotating 2 m radius centrifuge at 0, 23, or 30 rpm. RESULTS: No participants terminated the experiment due to motion sickness symptoms. Total mediolateral knee deflection increased by 1.0 to 2.0 cm during centrifugation, and did not result in any injuries. There was no evidence of an increased mediolateral knee travel "after-effect" during postrotation supine squats. Peak foot reaction forces increased with rotation rate up to approximately 200% bodyweight (iRED on ISS provides approximately 210% bodyweight resistance). The ratio of left-to-right foot force throughout the squat cycle on the centrifuge was nonconstant and approximately sinusoidal. Total foot reaction force versus knee flexion-extension angles differed between upright and AG squats due to centripetal acceleration on the centrifuge. DISCUSSION: A brief exercise protocol during centrifugation can be safely completed without significant after effects in mediolateral knee position or motion sickness. Several recommendations are made for the design of future centrifuge-based exercise protocols for in space applications. PMID- 22303589 TI - Net energy expenditure of gravity-independent high-speed resistive exercise done by women. AB - INTRODUCTION: Elevated metabolism is common to spaceflight while exercise in microgravity exacerbates energy costs. Thus in-flight exercise countermeasures must be devised that minimize energy costs as they are performed on hardware operable in microgravity. METHODS: Female subjects (N = 28), subdivided into athletic and sedentary groups, each performed two workouts on a resistive exercise device (Impulse Training Systems; Newnan, GA). Comprised exclusively of either tonic or phasic repetitions, each exercise bout entailed two 1 -min sets interspersed by a 90-s rest from which the work volume was determined. Oxygen consumption was measured before, during, and after workouts until gas uptake returned to pre-exercise levels. Net oxygen consumption was converted to net energy expenditures via indirect calorimetry. Mean net energy expenditure and work volume values were each compared with 2 (athletes, sedentaries) x 2 (tonic, phasic) ANOVAs, with repeated measures for workout. In addition, multivariate regression employed three predictor (body mass, body fat percentage, work volume) variables to account for the net energy expenditure variance. RESULTS: Workouts yielded a metabolic cost of approximately 14 kcal, yet the data produced no significant intergroup or workout differences. However, work volume analysis yielded a significant (tonic > phasic) effect. The multivariate analysis explained small yet significant amounts of net energy expenditure variance. DISCUSSION: Current results: 1) are partly attributable to higher series elastic element activity seen with Impulse repetitions; and 2) offer new information with respect to in-flight exercise protocols for female astronauts. PMID- 22303590 TI - Peripheral vascular responses of men and women to LBNP. AB - BACKGROUND: This study examined the hypothesis that women exhibit smaller vasoconstrictor responses in the calf during graded lower body negative pressure (LBNP). METHODS: Selective deep oxygenated hemoglobin (Hb) assessed by near infrared spectroscopy (NIRS) was used to examine blood flow changes in the calf. Eleven men and nine women volunteers underwent graded LBNP up to -60 mm Hg. Cardiovascular responses were measured by: NIRS on the forearm and superficial and deep calf for oxygenated and deoxygenated Hb; mercury strain gauge plethysmography for calf blood pooling; electrocardiogram for heart rate; and, photoplethysmography for blood pressure, cardiac output, and total peripheral resistance. RESULTS: Cardiac output was lower and total peripheral resistance higher in women; however, both men and women had similar decreases in cardiac output and increases in total peripheral resistance with LBNP. Forearm oxygenated Hb decreased from baseline throughout LBNP, and no difference was found between men and women. Female subjects had greater rates of increased blood pooling with LBNP than their male counterparts. Men had greater selective deep calf oxygenated Hb reductions compared to women during LBNP. Moreover, when the oxygenated Hb response as a function of calf blood pooling was examined with regression analyses, men had greater slopes (-0.62 +/- 0.05) than women (-0.33 +/- 0.04). CONCLUSION: The greater slopes in oxygenated Hb at given blood pooling and at each negative pressure in male subjects led us to conclude that men had greater vasoconstrictor responses in the calf during graded LBNP. PMID- 22303591 TI - Sleep-wake differences in heart rate variability during a 105-day simulated mission to Mars. AB - INTRODUCTION: In prolonged spaceflights the effect of long-term confinement on the autonomic regulation of the heart is difficult to separate from the effect of prolonged exposure to microgravity or other space-related stressors. Our objective was to investigate whether the sleep-wake variations in the autonomic control of the heart are specifically altered by long-term confinement during the 105-d pilot study of the Earth-based Mars500 project. METHODS: Before (pre), during (T1: 30, T2: 70, andT3: 100 d), and after (post) confinement, 24-h EKG records were obtained from the six crewmembers that participated in the mission. Sleep and wake periods were determined by fitting a square wave to the data. Autonomic activity was evaluated through time and frequency domain indexes of heart rate variability (HRV) analysis during wake and sleep periods. RESULTS: During confinement, wake HRV showed decreased mean heart rate and increased amplitude at all frequency levels, particularly in the very low (pre: 13.3 +/- 0.2; T1: 13.9 +/- 0.3; T2: 13.9 +/- 0.2; T3: 13.9 +/- 0.2; post: 13.2 +/- 0.2) and high (pre: 7.6 +/- 0.4; T1: 8.3 +/- 0.5; T2: 8.2 +/- 0.4; T3: 8.1 +/- 0.4; post: 7.6 +/- 0.3) frequency components (values expressed as mean +/- SE of wavelet power coefficients). Sleep HRV remained constant, while sleep-wake high frequency HRV differences diminished. DISCUSSION: The observed autonomic changes during confinement reflect an increase in parasympathetic activity during wake periods. Several factors could account for this observation, including reduced daylight exposure related to the confinement situation. PMID- 22303592 TI - Propranolol's potential to increase survival time in a disabled submarine. AB - BACKGROUND: While awaiting rescue from a disabled submarine, survivors will likely endure an atmosphere of rising CO2 that will result in CO2 toxicity once the available emergency CO2 scrubbing materials are exhausted. Propranolol is a beta-blocker that may increase survival time by reducing metabolic CO2 production (VCO2). The purpose of this study was to determine if propranolol reduces resting VCO2 in healthy men. METHODS: Eight healthy men completed a counterbalanced, randomized, placebo-controlled, double-blinded crossover study in which each subject received propranolol (40 mg twice daily) or placebo (lactose pill twice daily) over 72 h. The alternate condition was separated by a minimum 96-h washout period. Resting VCO2, oxygen consumption (VO2), ventilation (VE), respiration rate (RR), respiratory exchange ratio (RER), mean arterial pressure (MAP), heart rate (HR), and cardiac output (Q) were measured each morning and afternoon. RESULTS: When compared to placebo, propranolol significantly reduced VCO2 ( 6.5%), MAP (-3.6%), HR (-10.4%), and Q (-8.2%); however, there were no significant differences in VO2, RR, VE, or RER. DISCUSSION: These results show that 40 mg of propranolol taken twice daily reduces resting VCO2 in healthy men and suggests that this treatment strategy may increase survival time in a disabled submarine scenario. PMID- 22303593 TI - +Gz centrifugation and mood. AB - BACKGROUND: Physiological effects of +Gz centrifugation are well known. Psychological functioning combined with +Gz centrifugation also appears to be important, but has not yet been sufficiently studied. This study was designed to evaluate whether mood (energetic arousal, tense arousal, and hedonic tone) is influenced by a centrifuge run with +Gz stress. METHOD: We examined subjects' mood four times: 2 h prior to the centrifuge run, 2 min before and after centrifugation, and again 30 min afterwards. Energetic arousal (EA), tense arousal (TA), and hedonic tone (HT) assessments were conducted by the self reported UWIST Mood Adjective Check List (UMACL). RESULTS: Centrifugation explained 31.6% of EA and 56.9% of TA variance. EA level increased 2 min before centrifugation and remained so until the last measurement. TA was high 2 h prior to the centrifuge run, rose sharply 2 min before centrifugation, and lowered considerably after cessation of the run. The HT level was stable throughout all measurements. CONCLUSION: The centrifuge run with +Gz acceleration may evoke changes in arousal, but not in subjective enjoyment. Alterations in arousal levels triggered by centrifugation were positive, increasing energy and reducing tension. PMID- 22303594 TI - Aeromedical decision making and seizure risk after traumatic brain injury: longitudinal outcome. AB - INTRODUCTION: Traumatic brain injury (TBI) is common in young adults and therefore of significant concern to an aircrew population. This paper reports the occurrences of seizures in U.S. Air Force (USAF) aircrew following receipt of an aeromedical waiver for TBI. METHODS: Using both an aeromedical waiver tracking system database and medical records, we identified surrogate seizure markers such as all episodes of subsequent TBI, seizure, loss of consciousness, or prescription of anticonvulsant medications from the time of initial TBI until the last medical visit or entry recorded in either the database or medical records for our study population. RESULTS: The seizure rate for aircrew who met USAF waiver criteria was 24.53/100,000 person-years. One pilot experienced a major motor seizure 14.9 yr following a severe TBI for an incidence of 308.64/100,000 person-years. DISCUSSION: The USAF waiver process following TBI was sufficiently effective in removing aircrew with elevated risk for seizure following TBI. While our rates of post-traumatic seizure appear to be lower than previously published civilian population rates, direct comparison cannot be made secondary to differences in study design and selection criteria. Further areas of study could involve a more detailed analysis of aircrew neurocognitive status following TBI for subtle changes, crosschecking USAF Safety Center data for changes in accident rates among post-TBI aircrew, and analysis of lost aircrew flying time as a result of TBI and the degree of burden that loss places on the flying mission. CONCLUSION: Application of these stringent criteria is sufficient to fulfill aeromedical safety standards, but costs remain undetermined. PMID- 22303595 TI - Positional and rotational stability of the toric phakic intraocular lens under high +Gz environments. AB - BACKGROUND: Phakic intraocular lens (PIOL) implantation is a surgical option for correction of refractive errors. PIOLs can be use to correct myopia, hyperopia, and astigmatism. It is a surgical option available to patients in addition to methods such as laser cornea refractive surgery, e.g., laser assisted in-situ keratomileusis (LASIK) and photo-refractive keratectomy (PRK). Visian implantable collamer lens (ICL) are posterior chamber lenses which are surgically positioned in a phakic eye in the sulcus between the iris diaphragm and the natural crystalline lens. CASE REPORT: This case report describes the stability of Visian toric ICL in a candidate with bilateral implants under high +Gz force exposure in a human centrifuge trainer. The subject was sequentially exposed to three incremental +Gz profiles of +5 Gz, +7 Gz, and +9 Gz. Pre- and post-+Gz exposure, ophthalmic examination revealed no ICL displacement, implant touch or induced cataract, or change in refractive error. DISCUSSION: The rotational stability of the toric implants was also demonstrated by identical subjective refractions in both eyes taken pre- and post-+Gz, exposure. A search of the literature did not reveal any published articles on intraocular stability of ICL in the +Gz environment. This case report suggests that ICL may be considered an alternative to laser refractive surgery for patients subjected to a high +G, environment such as military aviators. PMID- 22303596 TI - Occupational cosmic radiation exposure of flight attendants may cause cancer. PMID- 22303597 TI - Cloud computing in biomedical research. PMID- 22303598 TI - You're the flight surgeon: diplopia. PMID- 22303599 TI - This month in aerospace medicine history. PMID- 22303600 TI - IL28B polymorphism -- predictive factor of HCV infected genotype 1 individuals to treatment response and management of therapy. AB - It is estimated that approximately 3% of the world population are chronically infected with HCV, as the annual incidence of HCV infection is approximately 3-4 million people. Despite all efforts made to eradicate the HCV infection, after the standard therapy (PegIFN and ribavirin for 48 weeks) only 40-50% of the HCV infected individuals with genotype 1 achieve sustained virological response (SVR). Since our goal today is the eradication of HCV infection, our prior concern has become the identification of predictor factors concerning treatment response. Recent studies such as GWAS have been concerned with the genetic factors and the response to treatment. Recently all interest has been turned towards the demonstration of the host polymorphism located upstream of the IL-28B gene and which is associated with sustained virological response to treatment with pegylated interferon Alfa in combination with ribavirin. Although 2011 comes with the FDA approval of the new triple therapy associating telaprevir/ boceprevir to the standard therapy, a new ethical concern regarding the high costs of this treatment rises the problem of who is the first in line? This is just the beginning of a new quest to further investigate the relationship between the host's polymorphism of the IL-28 gene and the standard and triple therapy in HCV infected individuals in achieving SVR as well as who should receive standard or triple therapy. Determination of the IL-28 polymorphisms may be used together with clinical assessment in order to evaluate patients and to personalize their treatment. The purpose of this paper is to underline the main concerns regarding the goal and endpoints of the HCV therapy, and the relationship of IL-28 in achieving sustained virological response, as well as in pointing out the importance to determine prior to initiating treatment the polymorphism of IL-28 since it is a strong predictor. This is important because it will increase the chances to achieve SVR, it will be cost-effective and reduces adverse effects. PMID- 22303601 TI - Early virological response in 1220 patients with HCV (genotype lb) chronic hepatitis and cirrhosis treated with PegInterferon plus Ribavirin. AB - There are over 5000 patients with genotype 1b HCV chronic infection in Romania on national waiting lists. This allowed us to evaluate the complete and partial early virological response rates (EVRc and EVRp), as well as the factors influencing the response rates to treatment. METHODS: PATIENTS: We studied 1220 treatment naive patients with HCV chronic hepatitis who started antiviral therapy during 2009. Mean age was 48 years and female gender was predominant (58%). Chronic hepatitis was documented by liver biopsy in 1129 patients (93%) or by non invasive tests in 91 cases (7%). Most patients presented advanced liver disease (F3 + F4 Metavir = 62.3%). Viral load was over 400000 iu/mL in 61% patients and over 600000 iu/mL in 52% patients. Treatment was performed with peginterferon alpha-2a in 75.2% patients and with peginterferon alpha-2b in 24.8% patients, with comparative histology. The influence of histology, viral load, gender, age and type of peginterferon on the response rates to treatment was evaluated. RESULTS: EVRc was obtained in 76.6% patients, while 16.2% presented EVRp. From those with EVRp, 78.8% had undetectable viral load after 6 months of therapy. The nonresponder rate was 9.6%. EVRc was influenced by viral load and age, but not by fibrosis stage or type of interferon. CONCLUSIONS: We noticed a high rate of EVRc, which was not influenced by histology, gender or type of interferon. The number of nonresponders and of patients who interrupted therapy due to lack of compliance or adverse events was low. PMID- 22303602 TI - Asymptomatic urinary anomalies, hematuria and proteinuria, in patients with inflammatory bowel disease. Preliminary study. AB - The study assesses the presence of asymptomatic urinary anomalies in patients with inflammatory bowel disease. Asymptomatic urinary anomalies are mainly due to glomerular nephritis, they being one of the forms of its manifestation, together with chronic nephrotic and nephritic syndromes. We identified urinary anomalies in 18 patients (20%) with bowel inflammatory disease that consisted of haematuria in 8 (9%) patients, isolated proteinuria in 5 (6%) patients and haematuria associated with proteinuria in 5 (6%) patients. Asymptomatic urinary anomalies were more frequent in patients with the Crohn disease than in those with ulcerative colitis. We identified RFG under 60ml/min in 4 patients with asymptomatic urinary anomalies. It is very easy to evaluate asymptomatic urinary anomalies with dipstick. This method is also required in current practice for patients with urinary anomalies for identifying the glomerular disease that might have caused them. One must take into consideration differential diagnosis with other diseases that can manifest themselves with proteinuria or isolated proteinuria. One must also take into account the fact that urinary anomalies may also be related to administration of 5-aminosalicylates. PMID- 22303603 TI - Detection of possible restriction sites for type II restriction enzymes in DNA sequences. AB - In order to make a step forward in the knowledge of the mechanism operating in complex polygenic disorders such as diabetes and obesity, this paper proposes a new algorithm (PRSD -possible restriction site detection) and its implementation in Applied Genetics software. This software can be used for in silico detection of potential (hidden) recognition sites for endonucleases and for nucleotide repeats identification. The recognition sites for endonucleases may result from hidden sequences through deletion or insertion of a specific number of nucleotides. Tests were conducted on DNA sequences downloaded from NCBI servers using specific recognition sites for common type II restriction enzymes introduced in the software database (n = 126). Each possible recognition site indicated by the PRSD algorithm implemented in Applied Genetics was checked and confirmed by NEBcutter V2.0 and Webcutter 2.0 software. In the sequence NG_008724.1 (which includes 63632 nucleotides) we found a high number of potential restriction sites for ECO R1 that may be produced by deletion (n = 43 sites) or insertion (n = 591 sites) of one nucleotide. The second module of Applied Genetics has been designed to find simple repeats sizes with a real future in understanding the role of SNPs (Single Nucleotide Polymorphisms) in the pathogenesis of the complex metabolic disorders. We have tested the presence of simple repetitive sequences in five DNA sequence. The software indicated exact position of each repeats detected in the tested sequences. Future development of Applied Genetics can provide an alternative for powerful tools used to search for restriction sites or repetitive sequences or to improve genotyping methods. PMID- 22303604 TI - The interplay of attention and self-monitoring with self-reporting oral health. AB - OBJECTIVES: We examined the effects of self-monitoring and focus of attention as predictors of self-reported oral health behaviors. MATERIAL AND METHODS: In this study of212 first year dental students, attention was measured with The Focus of Attention Questionnaire (FAQ) and self-monitoring with Revised Self-Monitoring Scale (SMS-R). The questionnaire included also information about socio demographic factors, self-reported oral health status and behaviors. RESULTS: Self-Focused Attention (FAQself) was statistically significantly higher in participants who reported more than only one gingival sign (such as gingival bleeding) compared with those who reported healthy gums. Significant differences were observed between the high and low self-monitors regarding the insatisfaction by appearance of own teeth, gingival health, dental visits and mouthrinse frequency. Relation between tootbrushing frequency and self-reported gingival status was moderated by Other-Focused Attention (FAQexternal). FAQexternal also emerged as a moderator for dental visit frequency and self-rated gingival status / dental decays. FAQself and FAQ were moderators for self-reported dental decays, dentist visit frequency and reasons for dental visiting. The relation between flossing frequency and self-rated gingival bleeding, between mouthrinse frequency and self-reported dental decays, between dental visit frequency or reason for dental visits and self-reported dental decays, between reason for dental visits and self-reported dental extractions was moderated by self-monitoring. CONCLUSIONS: The effect of focus of attention and self-monitoring should be considered when tailoring intervention efforts to oral health promotion as well as in studies involving self-reporting as a tool in screening the oral health of populations. PMID- 22303605 TI - Double transformation of a hematopoietic malignancy and severe associated thrombopathy. Case presentation and review of the literature. AB - We present the case of a patient with a double transformation during the evolution of chronic hematopoietic malignancy - JAK2 positive chronic myeloproliferative neoplasm; the first transformation had occurred previous to the presentation in our Department, but the second transformation was observed in evolution and it was into a rapidly evolving disease, followed by survival of less than one month. We underline the very poor prognosis -- overall survival of 2.5 years from initial presentation -- a much reduced survival for a chronic myeloproliferative neoplasm, probably due also to multiple associated pathology. Also, the other interesting element of the case is related to the dysfunctional platelets -- hemorrhagic complication at increased platelet count, respectively thrombosis at platelet count under 20000/mmc. PMID- 22303606 TI - Acute cerebellar infarcts in a young woman with beta-thalassemia major. AB - Beta-thalassemia major (beta-TM) is a rare genetic disorder that benefits from regular blood transfusions. Nevertheless some major complications arise from this life long treatment: hemolysis, hemochromatosis and a hypercoagulability state. Ischemic stroke may be another major complication. We present a patient with severe beta-TM diagnosed in early childhood who encountered all the first three complications and suffered a cerebellar ischemic stroke. In this case report we look over the possible physiopathological mechanisms that may have interfered in the onset and deployment of the ischemic event. We specify the neuroimagistic approaches that may be used in monitoring of these patients. In conclusion, we point out that there are many prothrombotic risk factors contributors to the hypercoagulable state that concurs to a cerebral infarct in a beta-TM patient. Careful monitoring and imagistic examination may select the patients at risk for a stroke event. PMID- 22303607 TI - Forensic necroptic epidemiology -- a useful method for the evaluation of renal, cardiac and cerebral lesions. Can it represent an addition to the information provided by clinical studies? AB - Our paper reviews the value of necroptic epidemiology in the evaluation of renal, cardiac and cerebral lesions. The necroptic epidemiology studies performed on American war casualties from Korea and Vietnam had practical implications in the prophylaxis of atherosclerosis in young age groups. The special interest they initially raised has been diminished by the advance of clinical studies that are nowadays dominant in the field of epidemiology. Given the fact that for the evaluation of certain diseases, such as chronic kidney disease, the morphological criterion is useful for the diagnostic, necroptic epidemiology can complete the epidemiological data provided by clinical studies. The use of data offered by forensic necroptic epidemiology can represent a reliable method for evaluating the epidemiology of certain diseases and of their complications. PMID- 22303608 TI - Loneliness updated: an introduction. PMID- 22303609 TI - Is loneliness the same as being alone? AB - The cognitive discrepancy model predicts that loneliness occurs when individuals perceive a difference between their desired and actual levels of social involvement. Using data from a sample of high school sophomore students, the present investigation was designed to go beyond previous research that has tested this model by examining the predicted nonlinear relationships between desired and actual social contact and feelings of loneliness. Analyses indicated that support for the cognitive discrepancy model of loneliness was found only for measures of close friendships. Specifically, the discrepancy between the students' ideal number and actual number of close friends was found to be related in a nonlinear fashion to feelings of satisfaction with close friendships and loneliness after control for the number of close friends. Implications of these findings for theoretical models of loneliness are discussed. PMID- 22303610 TI - Loneliness, optimism, and well-being among married, divorced, and widowed individuals. AB - The study explored feelings of loneliness and dispositional optimism and their unique contribution to well-being. The sample included 196 women and men (M age = 45.94 years; 54% were women; 34% were married, 34% were divorced, and 32% were widowed) who completed inventories assessing feelings of loneliness, dispositional optimism, and well-being measured by life satisfaction and negative affect. Widows and widowers scored higher than married respondents on loneliness and negative affect and lower on life satisfaction and optimism. Divorced persons scored lower on life satisfaction than married respondents but higher than widows and widowers on optimism. Loneliness was negatively correlated with optimism. Multiple regression analyses using demographics, family status, loneliness, and optimism as independent variables showed that loneliness contributed negatively to well-being, while optimism contributed positively to well-being. A Structural Equation Modeling analysis and mediation tests showed that both loneliness and optimism mediated the effects of widowhood on well-being. The findings are in support of Conservation of Resources (COR) theory (S. E. Hobfoll, 1989, 2001). PMID- 22303611 TI - Loneliness and emotional intelligence. AB - The possible associations of loneliness with Emotional Intelligence (EI), 2 of its correlates (life satisfaction and a sense of meaning), and several background variables were tested on a sample of 134 young adults attending college in northern Israel. Structural Equation Modeling (SEM) analysis provided support for the model, suggesting that the presence of meaning, EI, and size and availability of an individual's social network are the strongest correlates of loneliness. EI therefore emerges as a potentially important factor in our understanding of loneliness, and the model provides a framework for future studies. The results are discussed vis-a-vis existing findings in the literature and possible directions for approaching loneliness as a theoretical concept and a social phenomenon. PMID- 22303612 TI - Is it lonely at the top? An empirical study of managers' and nonmanagers' loneliness in organizations. AB - Loneliness is often assumed to be an occupational hazard for senior-ranked members of an organization. However, most of what researchers hear about being "lonely at the top" is anecdote. This article provides empirical evidence from three separate studies assessing loneliness in managers and nonmanagers. Across all three studies, loneliness did not differ by managerial status. Managers were no more or less lonely than their nonmanager counterparts. This suggests that factors beyond seniority may be contributing to loneliness in organizational settings. Ideas for future research are discussed. PMID- 22303613 TI - Children's loneliness, sense of coherence, family climate, and hope: developmental risk and protective factors. AB - The study examined the contributions of individual and familial variables for the prediction of loneliness as a developmental risk and the sense of coherence as a protective factor. The sample consisted of 287 children from grades 5-6. Their loneliness, sense of coherence, hope, effort, and family climate were assessed. Separate hierarchical multiple regression analyses revealed that family cohesion and children's hope contributed to the explanation of the risk and protective outcomes. Yet, the contribution of the family adaptability was not significant. Cluster analysis of the family climate dimensions (i.e., cohesion and adaptability) was performed to clarify the interactive roles of family adaptability together with family cohesion. The authors identified 4 separate family profiles: Children in the 2 cohesive families' clusters (Cohesive Structured Families and Cohesive Adaptable Families) reported the lowest levels of loneliness and the highest levels of personal strengths. Children within rigid and noncohesive family cluster reported the highest levels of loneliness and the lowest levels of children's sense of coherence. The unique role of the family flexibility within nonsupportive family systems was demonstrated. The results further clarified the unique profiles' characteristics of the different family clusters and their adjustment indexes in terms of loneliness and personal strengths. PMID- 22303614 TI - The prevalence of loneliness among adults: a case study of the United Kingdom. AB - Within contemporary Western (post) modern societies, loneliness is seen as a problem that is particularly associated with old age. Much less attention has been given to examining variations in loneliness across age groups. We examine patterns of loneliness across adults aged 15 years and older in the United Kingdom using data from the European Social Survey. We first consider the prevalence of loneliness among the adult population; then the relationship between loneliness and a range of key risk factors, and finally the relationship with age for each of our risk factors. Loneliness demonstrates a nonlinear U shaped distribution, with those aged under 25 years and those aged over 65 years demonstrating the highest levels of loneliness. Depression is associated with loneliness for all age groups. Poor physical health is associated with loneliness in young adult and midlife but not later life. For those in mid and later life, the quality of social engagement is protective against loneliness, while for young adults it is the quantity of social engagement. This indicates that different factors may endow vulnerability (or protect) against loneliness at different stages of life and suggests that preventative strategies or interventions that reflect these variations need to be developed. PMID- 22303615 TI - Association between loneliness and suicidality during middle childhood and adolescence: longitudinal effects and the role of demographic characteristics. AB - The association between loneliness and suicidality has been documented in many studies, but these studies have been limited by cross-sectional designs and the use of adult-only populations. The purpose of the current study was to overcome these limitations by (a) investigating whether the link between loneliness and suicidal thoughts and behaviors occurs cross-sectionally, longitudinally, or both and (b) investigating how the link between loneliness and suicidality might be influenced by different demographic variables, including gender, ethnicity, and socioeconomic status. Logistic regression analyses were used to analyze data from a large sample (N = 937) of youth from the NICHD Study of Early Child Care. Results indicated that loneliness at age 15 years was concurrently associated with both suicidal ideation and suicidal behavior at age 15 years. Loneliness in middle childhood was longitudinally associated with suicidal behaviors at age 15 years, but not with suicidal ideation at age 15 years. None of the demographic characteristics influenced these associations. PMID- 22303616 TI - Family of origin environment and adolescent bullying predict young adult loneliness. AB - This study tested parental loneliness, family of origin environment, and a history of being bullied as predictors of loneliness in young adults. The role of social skills in young adults' loneliness was also examined. Participants were 111 young-adult-parent dyads who completed measures of loneliness and the family communication environment. In addition, young adults completed measures of social skills and history of being bullied. Predictions were tested with structural equation modeling, path analysis, and multiple regression analysis. Results showed that parental loneliness and a history of being bullied were each significant predictors of young adult loneliness. A family environment that supported open communication was negatively associated with young adults' loneliness. Parental loneliness and a history of being bullied each had direct effects on young adults' loneliness as well as indirect effects through reduced social skills. PMID- 22303617 TI - "When it's just me at home, it hits me that I'm completely alone": an online survey of adolescents in self-care. AB - The present study examined adolescents' experiences of loneliness and solitude in their responses to an online survey on self-care. Both quantitative (n = 272) and qualitative (n = 150) responses were coded for these feelings when home alone. Results indicate that adolescents experience the duality of aloneness, including both positive solitude and negative loneliness. Adolescents' responses range from embraced solitude and self-care to feelings of loneliness and rejection of time by themselves. Adolescents reporting loneliness were significantly less likely to enjoy being home alone during the day and at night (p < or = .001). Also, gender, age, and emotions such as fear, boredom, and separation anxiety are associated with loneliness among adolescents in self-care. Interventions to increase connectedness and combat loneliness during out-of-school hours are recommended. PMID- 22303618 TI - Loneliness, depression, social support, and quality of life in older chronically ill Appalachians. AB - This study's purpose was to describe loneliness and to examine the relationships between loneliness, depression, social support, and QOL in chronically ill, older Appalachians. In-person interviews were conducted with a convenience sample of 60 older, chronically ill, community-dwelling, and rural adults. Those with dementia or active grief were excluded. The UCLA Loneliness Scale (Russell, Peplau, & Cutrona, 1985), Geriatric Depression Scale (Shiekh & Yesavage, 1986), Katz ADL scale (Katz, Down, & Cash, 1970), MOS Social Support Scale (Sherbourne & Stewart, 1991), and a visual analog scale for Quality of Life (Spitzer et al., 1981) scale were used. Diagnoses were obtained through chart reviews. SPSS was used for data analyses. The majority of the 65% female sample (M age = 75 years) were married and impoverished. Participants' number of chronic illnesses averaged more than 3. Over 88% of participants reported at least 1 area of functional impairment. Loneliness was prevalent with UCLA loneliness scores indicating moderate to high loneliness, ranging from 39 to 62 (possible scores were 20-80). Higher loneliness scores correlated with depression, lower Qol, and lower social support, particularly lower emotional support. This study provides evidence that loneliness is a significant problem for older chronically ill Appalachian adults and that it may be related to low emotional support. Further, it provides evidence that this population may be significantly lonely and may not self identify as lonely. Screening for loneliness and designing interventions that target the emotional aspects of loneliness could be important in this population. PMID- 22303619 TI - Life events and personality predicting loneliness among centenarians: findings from the Georgia Centenarian Study. AB - Regarding the purpose of this study, the researchers analyzed the roles that both life events (life-time positive events and life-time negative events) and personality (Neuroticism, Extraversion, Trust, Competence, and Ideas) played in participants of the Georgia Centenarian Study. The researchers analyzed these variables to determine whether they predicted loneliness. Analyses indicated that life-time negative events significantly predicted loneliness. In essence, the higher was the number of life-time negative life events, the higher was the loneliness score. Moreover, Neuroticism, Competence, and Ideas were all significant predictors of loneliness. The higher was the level of Neuroticism and intellectual curiosity, the higher was the level of loneliness, whereas the lower was the level of Competence, the higher was the level of loneliness. In addition, both life-time positive and life-time negative life events were significant predictors of Neuroticism. The higher was the number of life-time positive events, the lower was the level of Neuroticism, and the higher was the number of life-time negative events, the greater was the level of Neuroticism. These results indicated that life-time negative events indirectly affect loneliness via Neuroticism. Last, our results indicated that the Competence facet mediated the relationship between lifetime negative life events and loneliness. Life-time negative life events significantly affected centenarians' perceived competence, and Competence in turn significantly affected the centenarians' loneliness. These results as a whole not only add to our understanding of the link between personality and loneliness, but also provide new insight into how life events predict loneliness. PMID- 22303620 TI - No place like home? Potential pathways to loneliness in older adults under the care of a live-in foreign home care worker. AB - The arrangement in which frail older adults from the developed world are cared for in their homes by individuals from the developing world has become increasingly prevalent worldwide. In Israel, this arrangement is termed foreign home care. In this article, the authors first describe the global phenomenon of foreign home care of frail older adults as well as the more local characteristics of this arrangement in Israel. The authors then describe the concept of loneliness. Based on empirical and theoretical knowledge in the field of loneliness, the authors argue that older adults under live-in foreign home care may be particularly prone to feelings of loneliness for several reasons: some that are general to older adults with cognitive or physical disability and others that are specific to this particular caregiving arrangement. The authors conclude by providing ideas for future practice and research on this highly vulnerable group that, to date, has received only minimal research attention. PMID- 22303621 TI - Cross-national differences in older adult loneliness. AB - Loneliness concerns the subjective evaluation that the number of relationships is smaller than the individual considers desirable or that the intimacy that the individual wishes for has not been realized. The aim of this study was to assess variations in levels of late-life loneliness and its determinants across Europe. Data came from the SHARE surveys, Wave 2 (Borsch-Supan et al., 2008), encompassing adults aged 50 years and over in Austria, Belgium, the Czech Republic, Denmark, France, Germany, Greece, Ireland, Italy, the Netherlands, Poland, Spain, Sweden, and Switzerland (N = 12,248). Loneliness was measured by a single item derived from the CES-D (depression) scale. Using logistic models, the present authors tested several types of explanations for country differences: differences in demographic characteristics, wealth and health, and social networks. Older adults in the southern and central European countries were generally lonelier than their peers in the northern and western European countries. In the southern and central European countries, loneliness was largely attributable to not being married, economic deprivation, and poor health. Frequent contacts with parents and adult children, social participation, and providing support to family members were important in preventing and alleviating loneliness in almost all countries. To combat loneliness among older adults, the findings suggest both (a) generic approaches aimed at improving social embeddedness and (b) country-tailored approaches aimed at improving health and wealth. PMID- 22303622 TI - Loneliness in patients with rheumatic diseases: the significance of invalidation and lack of social support. AB - Rheumatic diseases affect about 20% of the population, leading to common symptoms such as joint problems, pain, fatigue, and stiffness. Loneliness is prevalent in individuals with rheumatic diseases. This could be due to not receiving social support and being stigmatized and invalidated, which might be most common in fibromyalgia, a rheumatic disease that lacks medical evidence. The aim of this study was to compare loneliness in distinct rheumatic diseases and to examine the association of loneliness with social support and invalidation. Participants were 927 patients with ankylosing spondylitis (n = 152), fibromyalgia (n = 341), osteoarthritis (n = 150), rheumatoid arthritis (n = 171), or systemic diseases (n = 113). They completed online questionnaires including an 11-point Likert scale assessing loneliness, the Illness Invalidation Inventory (3*1; Kool et al., 2010), and the Social Support Survey (SSS; De Boer, Wijker, Speelman, & De Haes, 1996; Sherbourne & Stewart, 1991). Patients with fibromyalgia experienced significantly more loneliness than patients with ankylosing spondylitis and patients with rheumatoid arthritis. Besides being younger, having lower education, and not working, in multiple regression analyses both lack of social support and invalidation were independently correlated with loneliness. This suggests that to decrease loneliness, therapeutic attention should be given to both increasing social support as well as decreasing invalidation in patients with rheumatic diseases, especially in patients with fibromyalgia. PMID- 22303623 TI - Loneliness and eating disorders. AB - This article examines the link between loneliness and eating disorders. This concept is evaluated through a systematic review of the literature that links loneliness and eating disorders and through a survey of themes connecting the 2 conditions. Eating disorders-including anorexia nervosa, bulimia nervosa, and eating disorders that are not otherwise specified, which include binge eating disorder-are challenging health issues. Each of these diagnoses specifically relates to loneliness. This negative emotion contributes to and fuels eating disorder symptoms. Negative interpersonal relationships, both real experiences and individuals' skewed perceptions, exacerbate eating disorders and feelings of loneliness. Characteristics that have been associated with loneliness clearly relate to eating disorders. Understanding this relationship is vital, so that we can appreciate our patients' struggles and work to target these intense emotions within the treatment setting. We need to be aware of the power of loneliness as it applies to individuals in general and specifically to those struggling with disordered eating. PMID- 22303624 TI - Loneliness and depressive symptoms: the mediating and moderating role of uncontrollable ruminative thoughts. AB - Although feelings of loneliness often are accompanied by depressive symptoms, little is known about underlying mechanisms in this association. The present study sampled 370 college freshmen and investigated whether rumination (and its components of Uncontrollability, Causal Analysis, and Understanding) functioned as a mediator or moderator in the relationship between 2 types of loneliness (as experienced in the relationship with parents and with peers, respectively) and depressive symptoms. Results indicated that rumination partially mediated the relationship between peer-related loneliness and depressive symptoms and moderated the relationship between parent-related loneliness and depressive symptoms. In addition, the uncontrollable nature, rather than the content, of these ruminative thoughts about parent- and peer-related loneliness was particularly harmful in the development of depressive symptoms. Implications and suggestions for future research are discussed. PMID- 22303625 TI - Injection of Acanthaster planci with thiosulfate-citrate-bile-sucrose agar (TCBS). I. Disease induction. AB - This is the first report of the successful induction of a transmissible disease in the coral-eating crown-of-thorns starfish Acanthaster planci (COTS). Injection of thiosulfate-citrate-bile-sucrose agar (TCBS) culture medium into COTS induced a disease characterized by discoloured and necrotic skin, ulcerations, loss of body turgor, accumulation of colourless mucus on many spines especially at their tip, and loss of spines. Blisters on the dorsal integument broke through the skin surface and resulted in large, open sores that exposed the internal organs. Oedema and reddened digestive tissues and destruction of connective fibers were common. Moreover, healthy COTS in contact with these infected animals also displayed signs of disease and died within 24 h. TCBS induced 100% mortality in injected starfish. There was no introduction of new pathogens into the marine environment. TCBS promoted the growth of COTS' naturally occurring Vibrionales to high densities with subsequent symbiont imbalance followed by disease and death. PMID- 22303626 TI - Injection of Acanthaster planci with thiosulfate-citrate-bile-sucrose agar (TCBS). II. Histopathological changes. AB - We assessed histological changes in the tissues of the crown-of-thorns starfish Acanthaster planci (COTS) after injection of thiosulfate-citrate-bile-sucrose agar (TCBS) which was used as a disease inducer (potential outbreak control method), by conventional and scanning electron microscopy. Digestive glands were processed and stained with hematoxylin and eosin to describe the histological architecture of the intestinal epithelium. Subsequently comparison of healthy versus infected tissues and Gram stains were carried out to confirm bacterial occurrence on infected tissues, characterize the structural changes induced by bacterial communities in COTS tissues, and to determine if the histopathological changes of intestinal tissues were consistent with vibrio infection. TCBS injections induced marked epithelial desquamation, hypertrophy and hypersecretion of glandular cells, epithelial cell destruction, pyknosis, reduction of thickness and disorganization of connective tissue and associated nerve plexus, presence of bacterial colonies, irregular eosinophilic foci in glandular cells, brush border disruption, atrophy and detachment of intestinal microvilli and cell debris in the lumen. All these changes were attributed to a fulminating systemic dysbiosis and were consistent with vibrio infections. PMID- 22303627 TI - Clinicoimmunopathologic findings in Atlantic bottlenose dolphins Tursiops truncatus with positive cetacean morbillivirus antibody titers. AB - Sera from free-ranging Atlantic bottlenose dolphins Tursiops truncatus inhabiting the Indian River Lagoon (IRL), Florida were tested for antibodies to cetacean morbilliviruses from 2003 to 2007 as part of a multidisciplinary study of individual and population health. A suite of clinicoimmunopathologic variables were evaluated in morbillivirus-seropositive dolphins (n = 14) and seronegative healthy dolphins (n = 49). Several important differences were found. Serum alkaline phosphatase, creatine phosphokinase, chloride, albumin and albumin/globulin ratios were significantly lower in seropositive dolphins. Innate immunity appeared to be upregulated with significant increases in lysozyme concentration and marginally significant increases in monocytic phagocytosis. Adaptive immunity was also impacted in dolphins with positive morbillivirus antibody titers. Mitogen-induced T lymphocyte proliferation responses were significantly reduced in dolphins with positive morbillivirus antibody titers, and marginally significant decreases were found for absolute numbers of CD4+ lymphocytes. The findings suggest impairment of cell-mediated adaptive immunity, similar to the immunologic pattern reported with acute morbillivirus infection in other species. In contrast, dolphins with positive morbillivirus antibody titers appeared to have at least a partially upregulated humoral immune response with significantly higher levels of gamma globulins than healthy dolphins, which may represent an antibody response to morbillivirus infection or other pathogens. These data suggest that subclinical dolphin morbillivirus infection in IRL dolphins may produce clinicoimmunopathologic perturbations that impact overall health. PMID- 22303628 TI - Re-examination of the prevalence of Aphanomyces astaci in North American crayfish populations in Central Europe by TaqMan MGB real-time PCR. AB - We applied quantitative TaqMan minor groove binder real-time polymerase chain reaction (PCR) on DNA isolates from soft abdominal cuticle of 460 North American crayfish Orconectes limosus and Pacifastacus leniusculus, previously tested for Aphanomyces astaci presence by conventional semi-nested PCR. Both approaches target the internal transcribed spacers of the pathogen nuclear ribosomal DNA, but apply different specific sequence motifs and technologies. The real-time PCR approach seems to provide higher sensitivity; the number of crayfish that tested positive increased from 23 to 32%, and 10 additional crayfish populations were indicated as hosting the disease agent. However, the vast majority of newly recorded positives contained very low agent levels, from 5 to 50 PCR-forming units. An isolate producing a false positive result by the semi-nested PCR (apparently undescribed Aphanomyces related to A. astaci) remained negative using the real-time PCR. The present study shows that previous results based on the semi-nested PCR were not substantially influenced by false positives but might have suffered from some false negatives at low agent levels. Combining alternative methods may therefore provide more reliable conclusions on the pathogen's presence. Further, we found positive correlation between the prevalence of infection carriers in American crayfish populations and the average amounts of A. astaci DNA detected in infected local crayfish individuals. PMID- 22303629 TI - Reptiles as potential vectors and hosts of the amphibian pathogen Batrachochytrium dendrobatidis in Panama. AB - Chytridiomycosis, the disease caused by Batrachochytrium dendrobatidis, is considered to be a disease exclusively of amphibians. However, B. dendrobatidis may also be capable of persisting in the environment, and non-amphibian vectors or hosts may contribute to disease transmission. Reptiles living in close proximity to amphibians and sharing similar ecological traits could serve as vectors or reservoir hosts for B. dendrobatidis, harbouring the organism on their skin without succumbing to disease. We surveyed for the presence of B. dendrobatidis DNA among 211 lizards and 8 snakes at 8 sites at varying elevations in Panama where the syntopic amphibians were at pre-epizootic, epizootic or post epizootic stages of chytridiomycosis. Detection of B. dendrobatidis DNA was done using qPCR analysis. Evidence of the amphibian pathogen was present at varying intensities in 29 of 79 examined Anolis humilis lizards (32%) and 9 of 101 A. lionotus lizards (9%), and in one individual each of the snakes Pliocercus euryzonus, Imantodes cenchoa, and Nothopsis rugosus. In general, B. dendrobatidis DNA prevalence among reptiles was positively correlated with the infection prevalence among co-occurring anuran amphibians at any particular site (r = 0.88, p = 0.004). These reptiles, therefore, may likely be vectors or reservoir hosts for B. dendrobatidis and could serve as disease transmission agents. Although there is no evidence of B. dendrobatidis disease-induced declines in reptiles, cases of coincidence of reptile and amphibian declines suggest this potentiality. Our study is the first to provide evidence of non-amphibian carriers for B. dendrobatidis in a natural Neotropical environment. PMID- 22303630 TI - Multiplex PCR for the detection of Piscirickettsia salmonis, Vibrio anguillarum, Aeromonas salmonicida and Streptococcus phocae in Chilean marine farms. AB - A multiplex (m-)PCR-based protocol was designed for the simultaneous detection of the main marine bacterial pathogens in Chilean salmon farms: Streptococcus phocae, Aeromonas salmonicida, Vibrio anguillarum and Piscirickettsia salmonis. Each of the 4 oligonucleotide primer pairs exclusively amplified the target gene of the specific bacterial pathogen. The detection limit of the m-PCR using purified total bacterial DNA was 50 pg microl(-1) for V anguillarum, 500 fg microl(-1) for P. salmonis, and 5 pg microl(-1) for S. phocae and A. salmonicida. This corresponded to average limits in the m-PCR sensitivity of 3.69 x 10(5) CFU ml(-1) of V anguillarum, 1.26 x 10(4) CFU m(-1) of S. phocae, and 5.33 x 10(4) CFU ml(-1) of A. salmonicida, while the detection limits for the spiked fish tissues, regardless of the sample (spleen, kidney, liver or muscle) were 2.64 +/- 0.54 x 10(7) CFU g(-1) for V. anguillarum, 9.03 +/- 1.84 x 10(5) CFU g(-1) for S. phocae, 3.8 +/- 0.78 x 10(3) CFU mg(-1) for A. salmonicida and 100 P. salmonis cells. However, high amounts of DNA from 3 bacterial species had a reduction of 1 log-unit on the amplification sensitivity of S. phocae or A. salmonicida when these were present in lower concentration in the multiplex reaction. The assay described in this study is a rapid, sensitive and efficient tool to detect the presence of S. phocae, A. salmonicida, V. anguillarum and P. salmonis simultaneously from pure cultures and tissues from clinically diseased fish. Therefore, it may be a useful alternative to culture-based methods for the diagnosis of infections in fish obtained from Chilean salmon farms. PMID- 22303631 TI - Histopathological and ultrastructural studies of the tapeworm Monobothrium wageneri (Caryophyllidea) in the intestinal tract of tench Tinca tinca. AB - Monobothrium wageneri is a monozoic caryophyllidean tapeworm of tench Tinca tinca. The pathological changes caused by this parasite within the intestinal tract of wild tench are described for the first time. Parasites were found attached to the anterior third of the intestine in tight clusters comprising up to 109 tapeworms. Infection was associated with the formation of raised inflammatory swellings surrounding the parasites. This host response, combined with the deep penetration of the scolex into the gut wall, formed a very firm seat of parasite attachment. Histopathological changes were characterised by a pronounced fibrogranulomatous lesion that extended through all layers of the intestine. This was accompanied by haemorrhage, oedema, necrosis and degeneration of the muscularis. A marked eosinophilic interface layer between the scolex of the tapeworm and gut wall indicated intimate host-parasite contact. Ultrastructural examinations revealed coniform spinitriches covering the neck and lateral sides of the scolex and capilliform filitriches present on the apical end of the scolex. Numerous glandular cytons (tegumental glands) were recorded throughout the scolex tegument. Large numbers of secretory granules discharged from the glands through a network of processes onto the scolex surface were consistent with distancing the cellular responses of the host. Observations of severe inflammatory lesions, partial intestinal occlusion and the potential for intestinal perforation represent important pathological changes that are consistent with loss of normal gut function. The lesions associated with the attachment of M. wageneri are more severe than those recorded for any other tapeworm of British freshwater fish. PMID- 22303632 TI - Vector potential of the salmon louse Lepeophtheirus salmonis in the transmission of infectious haematopoietic necrosis virus (IHNV). AB - To better understand the role of vector transmission of aquatic viruses, we established an in vivo virus-parasite challenge specifically to address (1) whether Lepeophtheirus salmonis can acquire infectious haematopoietic necrosis virus (IHNV) after water bath exposure or via parasitizing infected Atlantic salmon Salmo salar and if so, define the duration of this association and (2) whether L. salmonis can transmit IHNV to naive Atlantic salmon and whether this transmission requires attachment to the host. Salmon lice which were water bath exposed to 1 x 10(5) plaque-forming units (pfu) ml(-1) of IHNV for 1 h acquired the virus (2.1 x 10(4) pfu g(-1)) and remained IHNV-positive for 24 h post exposure. After parasitizing IHNV-infected hosts (viral titer in fish mucus 3.3 x 10(4) pfu ml(-1)) salmon lice acquired IHNV (3.4 x 10(3) pfu g(-1)) and remained virus-positive for 12 h. IHNV-positive salmon lice generated through water bath exposure or after parasitizing infected Atlantic salmon successfully transmitted IHNV, resulting in 76.5 and 86.6% of the exposed Atlantic salmon testing positive for IHNV, respectively. In a second experiment, only salmon lice that became IHNV positive through water bath exposure transmitted IHNV to 20% of the naive fish, and no virus was transmitted when IHNV-infected salmon lice were cohabitated but restrained from attaching to naive fish. Under laboratory conditions, adult L. salmonis can acquire IHNV and transmit it to naive Atlantic salmon through parasitism. However, the ephemeral association of IHNV with L. salmonis indicates that the salmon louse act as a mechanical rather than a biological vector or reservoir. PMID- 22303633 TI - First case of erysipelas in a free-ranging bottlenose dolphin (Tursiops truncatus) stranded in the Mediterranean Sea. AB - An adult female bottlenose dolphin (Tursiops truncatus) stranded alive and subsequently died several minutes later on the Mediterranean coast of Spain on 14 July 2010. Clinical examination revealed foam through the blowhole and rales upon lung auscultation. On venipuncture, the blood was abnormally dense and dark. Hematological and biochemical abnormalities included dehydration, leukocytosis (48 600 leukocytes microl(-1)) characterized by neutrophilia (48 200 neutrophils microl(-1)), and elevated bilirubin (4.38 mg dl(-1)), alanine aminotransferase (382.3 U l(-1)), aspartate aminotransferase (1449.3 U l(-1)), lactate dehydrogenase (1631.3 U l(-1)), and creatine kinase (404.7 U l(-1)). The most relevant findings of the gross examination were rhomboid-shaped skin lesions, stable froth in the trachea, pulmonary congestion, abnormally thick and rough pleura with adhesions, edematous and congestive superficial cervical and tracheobronchial lymph nodes, red-tinged urine, and severe brain congestion. Histopathology of the kidney, lung, skin, and brain revealed multisystemic intravascular bacterial emboli. Samples of skin, brain, and lung were cultured on Columbia blood agar under both aerobic and anaerobic conditions, and pure and heavy bacterial cultures were obtained from skin and brain samples. The microorganism isolated was Gram-positive, catalase-negative, facultatively anaerobic, and rod-shaped. The isolates were identified as Erysipelothrix rhusiopathiae by the API Coryne biochemical system. Based on the gross and microscopic findings, a diagnosis of acute E. rhusiopathiae septicemia was made. To the best of our knowledge, this is the first report of E. rhusiopathiae septicemia in a free-ranging bottlenose dolphin. PMID- 22303634 TI - Duplicated gallbladder: surgical application and review of the literature. AB - Duplicated gallbladder is a rare congenital anomaly, usually asymptomatic and occurring as incidental radiographic or surgical finding during upper abdomen, liver and extrahepatic biliary tract surgery. We report on a case of two separate gallbladders, one main and one accessory, each one with its own cystic duct. The main cystic duct drained into the common bile duct while the accessory bile duct extruded into the left side of common bile duct just inferior to the main cystic duct termination. Imaging advances such as computerized tomography, intraoperative endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography may aid in the establishment of accurate diagnosis. The anomaly is of great importance because the surgeon may miss the main or the accessory gallbladder and the patient may need to be re-operated in case of cholelithiasis. PMID- 22303635 TI - Concurrent variations of median and musculocutaneous nerves and their clinical correlation--a cadaveric study. AB - Variations of median nerve, musculocutaneous nerve and their communicating branches are of interest for anatomists and surgeons. These variations may be vulnerable to damage in surgical procedures. We examined median nerve and musculocutaneous nerve concurrently in 58 cadavers, i.e. 116 superior extremities, and found median nerve innervating muscle of the anterior compartment of arm in the absence of musculocutaneous nerve in 11.2% superior extremities, splitting of median nerve in the arm into median nerve proper and musculocutaneous nerve in 5.12% superior extremities, and communication between median and musculocutaneous nerves in 20.7% superior extremities. Knowledge of such anatomical variations is helpful for surgeons treating neoplasm or repairing trauma. PMID- 22303636 TI - AIDS since 1984: no evidence for a new, viral epidemic--not even in Africa. AB - Since the discoveries of a putative AIDS virus in 1984 and of millions of asymptomatic carriers in subsequent years, no general AIDS epidemic has occurred by 2011. In 2008, however, it has been proposed that between 2000 and 2005 the new AIDS virus, now called HIV, had killed 1.8 million South Africans at a steady rate of 300,000 per year and that anti-HIV drugs could have saved 330,000 of those. Here we investigate these claims in view of the paradoxes that HIV would cause a general epidemic in Africa but not in other continents, and a steady rather than a classical bell-shaped epidemic like all other new pathogenic viruses. Surprisingly, we found that South Africa attributed only about 10,000 deaths per year to HIV between 2000 and 2005 and that the South African population had increased by 3 million between 2000 and 2005 at a steady rate of 500,000 per year. This gain was part of a monotonic growth trajectory spanning from 29 million in 1980 to 49 million in 2008. During the same time Uganda increased from 12 to 31 million, and Sub-Saharan Africa as a whole doubled from 400 to 800 million, despite high prevalence HIV. We deduce from this demographic evidence that HIV is not a new killer virus. Based on a review of the known toxicities of antiretroviral drugs we like to draw the attention of scientists, who work in basic and clinical medical fields, including embryologists, to the need of rethinking the risk-and-benefit balance of antiretroviral drugs for pregnant women, newborn babies and all others who carry antibodies against HIV. PMID- 22303637 TI - From conception to birth: ancient library sources of embryology and women anatomy kept in the Biblioteca Biomedica of the Universita degli Studi di Firenze (Biomedical Library of Florence University). AB - The Biomedical Library of the University of Florence boasts a prestigious group of books collected at first in 1679 at the hospital "Santa Maria Nuova" and then continuously enriched in the course of time up today. The "Antique Collection" consists of 13 incunabola, hundreds of 16th-century books, more than one thousand books on medical subject from the 1600's, about six thousand 18th-century volumes and several large, valuable anatomical atlases. In this paper the most important, curious and fascinating books dealing with human ontogeny (from embryo generation to birth) and with female anatomy (mostly concerning pregnancy and childbirth) are reported in chronological order starting from the work of Hippocrates. Among the ancient sources useful for the reconstruction of the opinions about obstetrics there are also outstanding handbooks specifically edited for midwives. Many of these antique books are especially precious because they embed a great number of didactic pictures, some of which may compete against any modern book of anatomy, embryology and obstetric. Selected images from these books are shown. PMID- 22303638 TI - Gross morphometric study of the eyeball and tongue of the Nigerian local dog. AB - This study investigates the morphometry of two sense organs, the eyeball and tongue, of the Nigerian local dog (11 males, 14 females), all aged 2 years and above. The samples were grouped according to gender and weight (up to 12 kg or above that weight). The average values obtained for the weights of the left and right eyeballs and the tongue were 3.77 +/- 0.51 g, 3.68 +/- 0.74 g and 2.96 +/- 0.38 g respectively, while the length of the tongue, its thickness and width at the root and apex were 14.20 +/- 2.29 cm, 0.87 +/- 0.30 cm, and 0.21 +/- 0.05 cm respectively. The circumferences of the eyeballs (antero-posterior, mediolateral and peri-orbital) were all found to be higher in females, except the antero posterior circumference of left eye, in spite of heavier eyeballs in males. Also, the females showed a wider rima oris and higher values for most of the tongue measurements. A positive correlation existed between the weight of the animal and that of the head and tongue, while a negative correlation was observed between the body weight and the weight of the eyeballs. This report highlights the presence of sexual dimorphism and mild lateral asymmetry in this rarely reported breed of dog. The data obtained from this study may find application in feeding physiology, ophthalmic clinical manipulations and comparative anatomy. PMID- 22303639 TI - Anatomic variations of the cardiac valves and papillary muscles of the right heart. AB - This article reviews the right atrioventricular and pulmonary valves, along with their anatomic variations as well as the papillary muscles and chordae tendineae of the right ventricle of the human heart. A brief anatomical background is given for every structure, as well as a gross review of their embryological basis. Although the normal morphology of the right atrioventricular valve is tricuspid, this is not always the case; its anatomic variations involve, firstly, the number of cusps and accessory leaflets. Anatomic variations of the right atrioventricular valve may occur in association with other congenital anomalies and syndromes. Also the number, length and shape of the papillary muscles and chordae tendineae are variable. This can be of clinical significance since the papillary muscles play an important role in the contraction of the right ventricle and in the closure of the tricuspid valve so as to prevent ventricular blood from passing back into the right atrium. The pulmonary valve may present variations in the number of cusps, stenosis or atresia, either as isolated clinical findings or in association with congenital syndromes. PMID- 22303640 TI - Effect of polluted water from the Egyptian Eastern Mediterranean coast on reproductive, toxicological and hematological characteristics of Siganus rivulatus. AB - The impact of diluted levels of polluted seawater from the Egyptian Mediterranean coast on reproductive, toxicological and hematological characteristics of Siganus rivulatus were determined. Mature fish were exposed to diluted levels of 7.5, 10 and 15 ml L(-1) polluted seawater. Hematological changes after 4, 15 and 30 days of exposure were measured. Erythrocytes decreased (p<0.05) as well as Packed Cell Volume (PCV) and Hemoglobin (Hb), indicating anemia developed to hypochromic macrocytic anemia at end of experiment. Leukocytes, increased (p<0.05), indicating susceptibility of fish to infection and stress. Granulocytic leukocytes, neutrophil and eosinophil increased. While lymphocytes decreased. Blood parameters of exposed fish revealed compensatory responses. The increase in developing hemocytoplast and myelocytes emphasize the compensatory and defensive reaction of fish to polluted water. Exposure to polluted water levels has a detrimental effect on gonads development, altered endocrine haemostasis, testosterone and progesterone levels decreased in females (p<0.05). While in male, progesterone level increased (p<0.01). Necrosis of spermatogenic cells and atresia of developing oocytes are pronounced at levels of 10 and 15 ml L( 1)polluted seawater. Also, has necrotic effect on fish organs. Vacuolation and necrosis occurs in liver and kidney. Melanomacrophage aggregates can be seen. Gills showed epithetial lifting and vascular widening. Results showed that, polluted water has serious consequences on Siganus rivulatus blood characteristics as well as organs cellular structure. It rendered fish anemiatic, altered reproductive hormones level, leading to necrosis of males spermatogenic cells and atresia of developing oocytes. PMID- 22303641 TI - Intravenous dexamethasone versus morphine in relieving of acute migraine headache. AB - Inflammation is thought to play a significant role in the underlying pathophysiology of migraine headaches which could be controlled by corticosteroids. The present study was conducted to determine and compare the pain relieving effect of dexamethasone versus morphine on patients with acute migraine headache. During this double blinded clinical trial study, 190 patients who met the International Headache Society definition of acute migraine headache were evaluated at emergency department of Tabriz Imam Reza Hospital. After giving informed consent, patients were randomly enrolled into two groups: Receiving either 8 mg dexamethasone (group A) or 0.1 mg kg(-1) morphine (group B) intravenously. Severity of the headache was determined using Visual Analog Scale (VAS) scoring method at baseline (VAS-A), 10 min (VAS-B), 60 min (VAS-C) and 24 h (VAS-D) after intervention. The mean age of patients was 44.17 +/- 16.20 years, 61.57% male and 38.43% female. The mean of VAS-A and VAS-B scores was not statistically different between two groups (p = 0.236 and p = 0.481), but the mean of VAS-C and VAS-D scores in the group A were significantly lower than the group B (p = 0.017, p = 0.010). In long-term (1 h and 24 h after administration), dexamethasone reduces the severity of acute migrant headache more than morphine. PMID- 22303642 TI - Comparing the levels of trace metal from two fish species harvested from treated waste water in Pretoria, South Africa. AB - The persistent problem of water scarcity with the ever increasing demand of water has necessitated the reuse of effluent in agriculture. The present study evaluated the reuse of treated waste water and bioaccumulation properties of two fish species from a manmade lake. Trace metals content of two fish species: Clarias gariepinus and Cyprinus carpio and levels of trace metals from waste water in the lake where the fish species were harvested were determined by Inductive Couple Plasma-Optical Emission Spectrometer (ICP-OES). The trace metal values from fish samples ranged between 0.45-4.41 microg g(-1) for Cu, 16.45 72.23 microg g(-1) for Zn, 1.92-4.71 microg g(-1) for Cr, 2.45-5.65 microg g(-1) for Ni, 10.23-44.31 microg g(-1) for Mn, 9.67-46.59 microg g(-1) for Fe and 0.12 0.56 microg g(-1) for Pb. The carp exhibited a significantly higher concentration for the trace metals for all the parts analyzed (p<0.01). The levels of trace metals concentration from Cyprinus carpio was in the order liver>gill>muscle>bone and metal accumulation was in the order Zn>Fe>Mn>Cr>Ni >Cu>Pb. The concentration of trace metals such as zinc, iron, chromium and nickel were higher than the recommended legal limits for human consumption. The result revealed that properly treated waste water could be used for the purpose of aquaculture. Clarias gariepinus bio accumulated more trace metals from the lake when compared with Cyprinus carpio. PMID- 22303643 TI - Germination of Astragalus hamosus L. and Coronilla scorpioides (L.) as influenced by temperature. AB - Seed germination of two pasture legumes was tested under dark conditions at three alternating temperatures of 5-20, 15-20, 20-35 degrees C and constant 20 degrees C. Duration of the alternating temperatures was 12 h. The seedling counts were checked every day during four weeks. Species differed significantly in germination response to temperature. A. hamosus was more sensitive to temperature than C. scorpioides. The temperature of 20-35 degrees C was more favourable for the germination of A. hamosus than constant 20 degrees C which markedly reduced its germination. The interaction between accessions and temperatures for total germination was significant in both species. In A. hamosus, almost 50% of germination was achieved by all accessions by the first week at alternating 20-35 degrees C temperature while in C. scorpioides, average total germination was significantly low (4%) even by the 28th day. A total rate of 11 and 9% of germination were recorded by two accessions from Ouesslatia (210) and Agareb (19), respectively. A considerable variation for germination was observed among accessions of both species. Temperature requirements for seed germination of the studied species suggest why they are relatively easy or difficult to establish in the field. A. hamosus, with very small seeds required relatively high alternating temperature for germination than C. scorpioides which was insensitive to temperature and has relatively bigger seeds. PMID- 22303644 TI - Rapid urease test, touch cytology and histopathologic assessment in determining infection by Helicobacter pylori in outpatient setting. AB - Helicobacterpylori (HP) is a common cause of gastric infection with serious consequences which is detected by different methods. This study aimed at comparing the diagnostic value of Rapid Urease Test (RUT), Touch Cytology (TC) and histopathologic assessment in outpatients setting. In this cross-sectional study, 51 candidates for upper gastrointestinal endoscopy were recruited in Tabriz Imam Khomeini Teaching Centre in a 24 month period of time. Three biopsy specimens were obtained from gastric antrum during endoscopic intervention. The RUT, TC and histopathologic assessment were performed on each biopsy specimen in each patient. Definite infection by HP was considered when at least 2 out of 3 tests indicated presence of infection. Fifty one patients, 29 females and 22 males with a mean age of 40.10 +/- 12.54 (range: 18-72) years enrolled in this study. Infection by HP was definite in 41 cases (80.4%). The infection rates by RUT, TC and histopathologic examination were 82.4, 82.4 and 76.5%, respectively. The sensitivity, specificity and accuracy of RUT, TC and histopathologic assessment were 92.7, 60 and 66.75%; 100, 90 and 98% and 95.1, 100 and 96.1%, respectively. There were significant agreements between outcomes of the three methods in diagnosis of infection by HP. In conclusion, TC was the most sensitive and histopathologic assessment was the most specific method in diagnosis of infection by HP in outpatient setting. The diagnostic value of RUT was rather low in this regard. PMID- 22303645 TI - The focus is education. PMID- 22303646 TI - Challenges and issues facing the future of nursing education: implications for ethnic minority faculty and students. AB - Current trends in higher education in the United States demand that nursing take stock of how it is prepared or being prepared to face challenges and issues impacting on its future. The intense effort made to attract students to pursue advanced training in science and engineering in the United States pales in comparison to the numbers of science and engineering majors produced yearly in international schools. As a result, more and more jobs are being outsourced to international markets. Could international outsourcing become a method of nursing education? Authors submit that to remain competitive, the nursing profession must attract a younger cohort of technologically savvy students and faculty reflective of the growing diverse population in the United States. Additionally, nursing programs in research universities face even more daunting challenges as it relates to mandates for funded research programs of educational units. This article offers suggestions and recommendations for nursing programs in higher education institutions on ways to attract and retain ethnic minorities and of how to harness the power of research to address burgeoning societal health challenges. PMID- 22303647 TI - Playing the game: sports as a force for promoting improved academic performance for urban youth. AB - Using qualitative research methods involving observations and interviews with four students, their families and friends, this paper examines six ways that student involvement in sports promoted student success: structuring schedules, creating incentives, building confidence, developing positive adult and peer role models, and its role in getting students to develop future aspirations. It then turns to consider how students use their involvement with sports to negotiate the challenges they faced in adopting a successful student identity. Participation in school sports became a powerful justification for successful school performance for the participating students in this study. Finally, this paper ends with several policy implications for considering sports programming in urban schools. PMID- 22303648 TI - Descriptive study of student incivility in the People's Republic of China. AB - Disruptive student behavior is an emerging concern in institutions of higher education in the People's Republic of China (PRC). Faculty from a nursing college in the PRC expressed a desire to study the type and frequency of student incivility. Nursing faculty from the United States of America and the PRC collaborated on a study to measure faculty and student perceptions of student incivility in a Chinese nursing college. Student incivility in nursing education is a relatively new field of investigation; however, this preliminary study in the PRC shows it to be a substantial problem that needs to be addressed. PMID- 22303649 TI - An evaluation study of a mentoring program to increase the diversity of the nursing workforce. AB - Focus group methodology was used to evaluate faculty mentors (n = 10) and student mentees (n = 30) perceptions of a formal mentoring program. Prior to implementing the mentoring program, faculty preparation involved cultural competence and mentor workshops. Overall, both mentors and mentees had positive perceptions of the program. Three themes emerged from each group. The mentor themes were role modeling, caring and academic success and the mentee themes were support system, enhanced perceptions of the nursing profession, and academic enrichment. In addition, there were similarities between the mentors and the mentees when asked what constituted a good mentor and a good mentee. PMID- 22303650 TI - Let us in: Latino underrepresentation in Gifted and Talented Programs. AB - This paper articulates the necessity of improving identification protocols for inclusion of low-socioeconomic gifted Latino students in Gifted and Talented Programs in all levels of education ranging from elementary and continuing on to the college level. Non-verbal tests, observation instruments, grade-to-grade portfolios, performance projects, and extensive interviewing are suggested in lieu of biased standardized tests as identification variables. In addition, teacher professional development opportunities as well as the inclusion of multicultural curriculum will promote an appreciation of Latino culture as well as encourage and include intellectually gifted Hispanic students. Reference to collectivistic societal constructs impacting on positive Latino student engagement is discussed. This article will appeal specifically to those individuals entrusted with recruitment for elementary and secondary Gifted and Talented Programs as well as College Honors Programs. In addition, the notion that the identification of giftedness is culture dependent is of importance to the general public in our endeavor to become a multicultural globalist society. PMID- 22303651 TI - [Effect of opening degree regulation on diameter and height increment and aboveground biomass of Korean pine trees planted under secondary forest]. AB - Taking mixed forest of artifical Pinus koraiensis and natural broad-leaved trees as test material, among which the P. koraiensis was 15 (stage I) and 22 (stage II) years old respectively, and was in the same succession layer, the height and diameter increment during 4 years experimental period and the aboveground biomass (AGB) at the 4th experimental year for P. koraiensis were measured in the opening degree (K = 1.0, 1.5, 2.0) regulation experiment. The periodic increment of basal diameter (BD)/diameter at breast height (DBH), tree height and AGB of P. koraiensis trees were highest in the opening degree K = 1.0 treatment. The opening degree K = 1.5 and K = 2.0 treatments promoted the annual increment of P. koraiensis, with the effect increased along with the experimental period elongation and approached or exceeded that of K = 1.0 treatment. The stem biomass proportion of P. koraiensis trees was significantly higher in K = 1.0 treatment than that in the other treatments and the control in stage I, but no significant difference among treatments was found in stage II. The ratio of branch to needle biomass in all opening degree treatments was also significantly higher than that in control in stage I, but no significant difference in stage II. The proportion and distribution of needles in different ages differed in the two stages. It was concluded that opening degrees of 1.0-2.0 were all suitable for the growth of P. koraiensis of 15-22 years old trees planted under secondary forest. PMID- 22303652 TI - [Spatial structural characteristics of natural Populus davidiana - Betula platyphylla secondary forest]. AB - This paper analyzed the spatial structural characteristics of natural Populus davidiana - Betula platyphylla secondary forest in a 4 hm2 plot of Mulan Paddock, based on the diameter distribution and the spatial structure parameters mingling degree, neighborhood comparison, and angle index. In the forest, the diameter distribution of the stands presented as an inverse 'J' curve, the average mingling degree was 0.4, with the individuals at weak and zero mingling degree reached 51.6%, and the average mingling degree of P. davidiana and B. platyphylla was 0.25 and 0.39, respectively. The neighborhood comparison based on the diameter at breast height (DBH) and tree height was almost the same, suggesting that the P. davidiana and B. platyphylla were in the transition state from subdominant to middle. The horizontal distribution pattern had a close relation to the minimum measured DBH, being clustered when the DBH was > or = 1 cm and < 6 cm, and random when the DBH was > or = 6 cm. PMID- 22303653 TI - [Spatial distribution pattern of Picea schrenkiana var. tianshanica population and its relationships with topographic factors in middle part of Tianshan Mountain]. AB - By the method of point pattern analysis, this paper studied the spatial distribution patterns of different age class individuals in the Picea schrenkiana var. tianshanica forest in middle part of Tianshan Mountain and the influence of topographic factors on the distribution patterns. It was observed that the density of different age class individuals in the forest decreased with the increasing DBH of the individuals, and except old trees which presented a random distribution at the scale of 0-12 m, the saplings and the small, medium, and big trees were in aggregative distribution at all scales. With the increase of age class, the scale at which the individuals presented the highest aggregation degree increased, whereas the aggregation intensity declined. At small scale (0 16 m), different age class individuals appeared negative association, and the greater difference the tree age, the more significant the negative association presented. Altitude had significant positive effects on the number of medium, big, and old trees but had little effects on the number of saplings and small trees. Slope grade had significant positive effects on the number of saplings and small and medium trees, significant negative effects on the number of old trees, but little effects on the number of big trees. Concavo-convex had significant negative effects on the number of saplings and small and medium trees but had little effects on the number of big and old trees. PMID- 22303654 TI - [Dynamics of Quercus variabilis seed rain and soil seed bank in different habitats on the north slope of Qinling Mountains]. AB - In order to explore the dynamics of Quercus variabilis seed rain and soil seed bank in different habitats on the north slope of Qinling Mountains, three kinds of micro-habitats (understory, forest gap, and forest edge) were selected, with the seed rain quantity and quality of Q. variabilis, seed amount and viability in soil seed bank, as well as the seedling development of Q. variabilis studied. The seed rain of Q. variabilis started from mid August, reached the peak in mid September-early October, and ended at the beginning of November, and there existed differences in the dissemination process, occurrence time, and composition of the seed rain among the three micro-habitats. The seed rain had the maximum intensity (39.55 +/- 5.56 seeds x m(-2)) in understory, the seeds had the earliest landing time, the longest lasting duration, and the highest viability in forest gap, and the mature seeds had the largest proportion in forest edge, accounting for 58.7% of the total. From the ending time of seed rain to next August, the total reserve of soil seed bank was the largest in understory and the smallest in forest edge. In the three habitats, the amount of mature and immature seeds, that of seeds eaten by animals, and the seed viability in soil seed bank all decreased with time. In contrast, the number of moldy seeds increased. The seeds were mainly concentrated in litter layer, a few of them were in 0-2 cm soil layer, and few were in 2-5 cm soil layer. The density of the seedlings varied with habitats, being the largest in forest gap, followed by in forest edge, and the least in understory, which suggested that forest gap was more suitable for the seed germination and seedling growth of Q. variabilis, and thus, appropriate thinning should be taken to increase forest gap to provide favorable conditions for the natural regeneration of Q. variabilis forest. PMID- 22303655 TI - [Phosphorus characteristics in rhizosphere soil of Cunninghamia lanceolata, Pinus massoniana and their mixed plantations]. AB - In 2007-2010, a comparative study was conducted on the phosphorus characteristics in the rhizosphere soil of Cunninghamia lanceolata, Pinus massoniana and C. lanceolata-P. massoniana mixed plantations in a forest farm in Nanping City of Fujian Province, East China. In the rhizosphere soil of pure C. lanceolata and P. massoniana plantations, the content of available P was higher than that in non rhizosphere soil. As compared with non-rhizosphere soil, the rhizophere soil in the three plantations had lower pH and O-P content but higher Al-P and Fe-P contents, and its P adsorption capacity was lower while the P desorption rate and desorbed P were in adverse. In the rhizophere soil of pure P. massoniana plantation, the contents of available P, Fe-P, and Al-P, their desorption rates, and desorption capacity were higher, but the O-P content and the adsorbed P were lower, as compared with those in the rhizophere soil of pure C. lanceolata plantation. In the mixed plantation, the P activation in rhizophere soil was further improved, being more obvious under C. lanceolata, which suggested that mixed plantation of C. lanceolata and P. massoniana could promote the phosphorus nutrition of C. lanceolata. PMID- 22303656 TI - [Altitudinal patterns of flower plant biomass on alpine and subalpine meadow in Balang Mountains]. AB - A field survey was conducted to study the altitudinal patterns of flower plant biomass on alpine and subalpine meadow in Wolong Nature Reserve in Balang Mountains, and the soil factors were analyzed. With the increase of altitude, the aboveground biomass, including the biomass of flower-fruit, stem, and leaf, varied in unimodal and peaked at 3500 m a. s. l., the belowground biomass varied in U-shape, the soil acidity and the contents of soil hydrolyzable N and total K increased significantly, whereas the contents of soil organic matter, total N, and available P had a significant decrease. The aboveground biomass of the flower plants increased significantly with increasing soil pH and soil total N and available K contents, and the belowground biomass of the plants increased significantly with increasing soil organic matter and available P contents but decreased significantly with increasing soil total K and hydrolyzable N contents. PMID- 22303657 TI - [Responses of Cynodon dactylon population in hydro-fluctuation belt of Three Gorges Reservoir area to flooding-drying habitat change]. AB - This paper studied the population density, morphological characteristics, and biomass and its allocation of Cynodon dactylon at different altitudinal sections of the hydro-fluctuation belt in Three Gorges Reservoir area, based on located observations. At the three altitudinal sections, the population density of C. dactylon was in the order of shallow water section (165-170 m elevation) > non flooded section (above 172 m elevation) > deep water section (145-150 m elevation), the root diameter and root length were in the order of deep water section > shallow water section > non-flooded section, the total biomass, root biomass, stem biomass, leaf biomass, and stem biomass allocation ratio were in the order of the shallow water section > non-flooded section > deep water section, and the root biomass allocation ratio, leaf biomass allocation ratio, and underground biomass/aboveground biomass were in the order of deep water section > shallow water section > non-flooded section. The unique adaption strategies of C. dactylon to the flooding-drying habitat change in the shallow water section were the accelerated elongation growth and the increased stem biomass allocation, those in the deep water section were the increased node number of primary and secondary branches, increased number of the branches, and increased leaf biomass allocation, whereas the common strategies in the shallow and deep water sections were the accelerated root growth and the increased tillering and underground biomass allocation for preparing nutrition and energy for the rapid growth in terrestrial environment. PMID- 22303658 TI - [Effects of drought stress and re-watering on the active oxygen scavenging system of Cupressus funebris seedlings in Karst area]. AB - This paper studied the active oxygen scavenging system of Cupressus funebris seedlings under drought condition and the recovery capability of the system after re-watering, aimed to understand the adaptation mechanisms of C. funebris to the 'drought and re-watering' environment in Karst area. With the increasing time of drought stress, the seedling's relative water content (RWC) decreased, soluble protein concentration increased first and decreased then, and malondialdehyde (MDA) content increased consistently. The MDA content recovered to the level of the control (CK) when re-watering was implemented within 2 weeks of drought, but could not when the re-watering was made after 4 and 6 weeks of drought. Under drought stress, the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) increased consistently. After rewatering, the SOD activity had somewhat decrease but still remained at a higher level than the CK, and the POD and CAT activities decreased to the CK level when suffered mild stress but had less decrement when suffered severe stress. It was concluded that C. funebris seedlings could resist mild drought stress via increasing their soluble protein concentration and inhibiting membrane lipid peroxidation, but could not resist severe drought stress because of the irreversible damage of their membrane structure. PMID- 22303659 TI - [Effects of altitudinal gradient on Salix atopantha foliar delta13C]. AB - In 2010, measurements were conducted on the foliar delta13C, photosynthesis, CO2 diffusive conductivity, nitrogen content, photosynthetic nitrogen use efficiency (PNUE), and special leaf area (SLA) of Salix atopantha at different altitudes (2350 m, 2700 m, 3150 m, and 3530 m) in Wolong Natural Reserve. With the increase of altitude, the foliar nitrogen content (especially the nitrogen content per unit leaf area, N(area)) and the PNUE increased, and the foliar delta13C had a significant increase, with an increment of 1.4 per thousand per 1000 m altitude. The stomatal and mesophyll CO2 diffusion conductance also increased with increasing altitude, which had definite negative effect on the increase of foliar delta13C, but the effect was not strong enough. Comparing with CO2 diffusion conductance, carboxylation capacity was a more important factor limiting the P(c)/P(a), and even, the foliar delta13C. At altitude 2350-2700 m, air temperature was the main factor affecting the allocation of nitrogen in S. atopantha photosynthetic system, whereas at altitude 2700-3530 m, light could be the main affecting factor. No significant difference was observed in the SLA at different altitudes. PMID- 22303660 TI - [Regulation effects of short sunlight on two electron transport pathways in nectarine flower bud during dormancy induction]. AB - Taking the nectarine variety 'Shuguang' (Prunus persica var. nectariana cv. Shuguang) as test material, and by using respiration inhibitors KCN and SHAM, this paper studied the cytochrome electron transport pathway and the alternative respiration pathway in nectarine flower bud during dormancy induction under the effects of short sunlight. Both the total respiration rate (V(t)) and the cytochrome electron transport pathway respiration rate (rho' V(cyt)) presented double hump-shaped variation. Short sunlight brought the first-hump of V(t) and rho' V(cyt), forward and delayed the second-hump synchronously, inhibited the rho' V(cyt), but had no significant effects on the V(t). The capacity (V(alt)) and activity (rho V (alt)) of alternative respiration pathway also varied in double hump-shape, and the variation was basically in synchronous. Short sunlight made the first climax of V(alt) and rhoV(alt) advanced, but had little effects on the later period climax. The inhibition of cytochrome electron transport pathway and the enhancement of alternative respiration pathway were the important features of nectarine flower bud during dormancy induction, and according to the respective contributions of the two electron transport pathways to the total respiration rate, the cytochrome electron transport pathway was still the main pathway of electron transport, whereas the alternative respiration pathway played an auxiliary and branched role. PMID- 22303661 TI - [Transcriptional levels of AQPs genes in peach floral buds during dormancy]. AB - Taking the floral buds of 10 years old field-cultivated and 3 years old potted nectarine (Prunus persica var. nectarine cv. Shuguang) as test materials, and by the method of real-time quantitative PCR, this paper studied the expressions of the AQPs genes deltaTIP1 and PIP1; 1 during dormancy and dormancy-release (September 15, 2009-January 15, 2010) and the transcriptional levels of the genes under low temperature stress. Within the period of dormancy and dormancy-release, the transcriptional level of PIP1; 1 presented a persistent increasing trend, and the high level expression of PIP1; 1 in January could be related to the efflux of water through cytoplasma membrane and vacuolar membrane, which protected the bud cells from ice crystal injuries. The contents of soluble sugar, soluble protein, and proline in the bud cells all peaked in January, which prevented the excessive water loss from the cells. After 2 weeks of low temperature treatment, the PIP1; 1 had a high level expression, indicating that it was a cold-induced gene. The transcriptional level of deltaTIP1 fluctuated during dormancy, and increased significantly during dormancy-release, which might be induced by the dormancy release signals in buds and the resumption of plant activity. After 2 weeks of low temperature treatment, the expression level of deltaTIP1 had no increase, indicating that deltaTIP1 was not a cold-induced gene. PMID- 22303662 TI - [Assessment of rice achievable productivity and its application in rice production management division: a case study in Fuyang County of Zhejiang Province, East China]. AB - Rice productivity is the key factor affecting rice production and its sustainable development. Based on the gradation of cultivated land quality at county-level, this paper evaluated the rice productivity in Fuyang County of Zhejiang Province, and, through selected sampling field investigation and according to the land productivity index of paddy field quality, a model for assessing rice achievable productivity was established, aimed to analyze the regional rice productivity and its achievable productivity. In the study area, there was a positive correlation between the land productivity index and rice yield. For single cropping rice, its achievable productivity was 1.70 x 10(5) t, being 1.6 times of its realistic productivity (1.04 x 10(5) t). In 2009, the realistic rice productivity per unit area was 7676 kg x hm(-2), and the achievable productivity was 8831 kg x hm(-2), with a production potentiality of +15%, a big potential of rice production capacity in the county. Through the analyses of rice productivity, relative superiority of rice production scale, and its growth potential index in the villages and towns, the rice production of Fuyang County was divided into three regions, i. e., key enhancement region, optimization construction region, and development protection region. PMID- 22303663 TI - [Responses of rice-wheat rotation system in south Jiangsu to organic-inorganic compound fertilizers]. AB - In 2006-2007, a field trial was conducted to study the effects of applying three kinds of organic-inorganic compound fertilizers [rapeseed cake compost plus inorganic fertilizers (RCC), pig manure compost plus inorganic fertilizers (PMC), and Chinese medicine residues plus inorganic fertilizers (CMC)] on the crop growth and nitrogen (N) use efficiency of rice-wheat rotation system in South Jiangsu. Grain yield of wheat and rice in the different fertilization treatments was significantly higher than the control (no fertilization). In treatments RCC, PMC and CMC, the wheat yield was 13.1%, 32.2% and 39.3% lower than that of the NPK compound fertilizer (CF, 6760 kg x hm(-2)), respectively, but the rice yield (8504-9449 kg x hm(-2)) was significantly higher than that (7919 kg x hm(-2)) of CF, with an increment of 7.4%-19.3%. In wheat season, the aboveground dry mass, N accumulation, and N use efficiency in treatments RCC, PMC, and CMC were lower than those of CF, but in rice season, these parameters were significantly higher than or as the same as CF. In sum, all the test three compound fertilizers had positive effects on the rice yield and its nitrogen use efficiency in the rice wheat rotation system, being most significant for RCC. PMID- 22303664 TI - [Oat growth and cation absorption characteristics under salt and alkali stress]. AB - This paper monitored the oat growth and cation absorption characteristics on a saline-alkali soil in the Baicheng region of Jilin Province under low, medium, and high levels of salt stress. No significant differences were observed in the shoot growth and yield components under the three levels of salt stress, but the root biomass and root/shoot ratio decreased significantly with increasing salt stress level. At maturing stage, the root/shoot ratio under medium and high salt stresses was 77.2% and 64.5% of that under low salt stress, respectively. Under the three levels of salt stress, the K+/Na+ and Ca2+/Na+ ratios in oat plant had significant differences at trefoil stage, but no significant differences at heading stage. With the increase of salt stress level, the cation absorption selectivity coefficient of oat at filling stage decreased significantly, but the transportation selectivity coefficient had no significant difference under the three levels of stress. It was concluded that oat could adapt to the salt and alkali stress of soda-alkaline soil to some extent, and the adaptation capability decreased with the increasing level of stress. The decrease of oat root biomass and the stronger ion selective absorption capacity at heading stage under salt and alkali stress could benefit the shoot growth and yield components of oat. PMID- 22303665 TI - [Effects of NaCl stress on polyamines metabolism in vegetable soybean]. AB - By adopting vermiculite culture, this paper studied the malondialdehyde (MDA) content and polyamines (PAs) metabolism in the seeds of two vegetable soybean cultivars with different salt tolerance under the stress of 100 mmol NaCl x L( 1). NaCl stress increased the MDA contents in the seeds of the two cultivars significantly, but the increment was lower for salt-resistant cultivar 'Lulingtezao' (LL) than for salt-sensitive cultivar 'Lixianggaochan 95-1' (LX). In the whole period of NaCl stress, LL seeds had higher contents of free spermine (Spm), conjugated Spm, conjugated spermidine (Spd), bound Spd and bound putrescine (Put), higher values of (Spd+Spm)/Put and (cPAs+bPAs)/fPAs, and lower value of Put/PAs, and had higher content of free Spd in the mid and late period (9-15 d) of NaCl stress, as compared with LX seeds. In a longer term (6-15 d) of the stress, LL seeds maintained a higher activity of arginine decarboxylase (ADC) and a lower activity of polyamine oxidase (PAO). All the results suggested that LL seeds had stronger capabilities for polyamines synthesis and for the transformation of Put to Spd and Spm and of free polyamine to conjugated and bound polyamines, which effectively inhibited the membrane lipid peroxidation, possibly being one of the important reasons for the stronger salt tolerance of LL. PMID- 22303666 TI - [Impacts of suboptimal temperature and low light intensity on the activities and gene expression of photosynthetic enzymes in cucumber seedling leaves]. AB - Taking the cucumber cultivar 'Jinyou 3' as test material, this paper studied the variations of the mRNA expression and activities of ribulose-1, 5-bisphosphate carboxylase/oxygenase (Rubisco), fructose-1, 6-bisphosphatase (FBPase), glyceraldehydes-3-phosphate dehydrogenase (GAPDH), fructose-1, 6-bisphosphate aldolase (FBA), and transketolase (TK) in cucumber seedling leaves under suboptimal temperature and low light intensity (ST+LL). In the treatment of ST+LL, the leaf area and the dry mass per plant decreased remarkably, compared with the control. On the early days of ST+LL treatment, the gene expression of Rubisco rbcL and rbcS, FBPase, GAPDH, FBA, and TK declined markedly, the activities of the enzymes except TK obviously weakened, and the photosynthetic rate (P(n)) decreased rapidly. 3 days later, the gene expression of Rubisco rbcL and rbcS and the initial activity of Rubisco showed a continuous decrease but the decrement was obviously lesser, the total activity of Rubisco and the activities and gene expression of FBPase, GAPDH, FBA, and TK had an increasing trend, and the P(n) ascended simultaneously. When the treating time exceeded 6 days, the gene expression and the activities of Rubisco and FBPase tended to be constant, while those of the other enzymes as well as the P(n) presented a decreasing trend. These results suggested that the decline of the gene expression and activities of the photosynthetic enzymes in cucumber seedlings under suboptimal temperature and low light intensity was the important reason which led to the decrease of P(n). The adaptation of photosynthetic apparatus in cucumber seedlings to suboptimal temperature and low light intensity was related to the activation mechanisms of photosynthetic enzymes. PMID- 22303667 TI - [Accumulation characteristics of applied cinnamic acid in cucumber seedling-soil system under NaCl stress]. AB - Taking cucumber cultivars' Jinlv No. 5' (salt-tolerant) and 'Jinyou No. 1' (salt sensitive) as test materials, a pot experiment was conducted to study the effects of applying cinnamic acid on the accumulation of applied cinnamic acid in cucumber seedling-soil system under NaCl (585 mg x kg(-1) soil) stress. The concentration of applied cinnamic acid was the main factor affecting the accumulation of the exogenous cinnamic acid in the cucumber plant and soil. With the increasing concentration of applied cinnamic acid, except in the treatment of highest concentration (200 mg x kg(-1) soil) cinnamic acid, the total content of cinnamic acid in cucumber plant was increased. NaCl stress enhanced the toxicity of cinnamic acid. In the treatments of low and medium concentration cinnamic acid, the cinnamic acid content in cucumber plant increased; whereas in the treatments of high concentration cinnamic acid, the decline of the seedlings growth was observed, and led to the decrease of the cinnamic acid content in the plant. The content of cinnamic acid in 'Jinlv No. 5' plant decreased at the concentration of applied cinnamic acid being > 200 mg x kg(-1) soil, while that in 'Jinyou No. 1' started to decrease when the concentration of applied cinnamic acid was > 100 mg x kg(-1) soil, reflecting the discrepancy in salt tolerance of the two cultivars. For the cucumber plant, its leaf had the highest content of cinnamic acid. In the cucumber seedling-soil system, most of applied cinnamic acid was mainly accumulated in soil. PMID- 22303668 TI - [Effects of applying calcium on peanut physiological characteristics, its yield and kernel quality under cadmium stress]. AB - Taking high-oil peanut cultivar Yuhua15 and high-protein peanut cultivar XB023 as test materials, a pot experiment was conducted in both 2009 and 2010 to study the effects of applying different concentration calcium (Ca) on the vegetative growth, leaf chlorophyll content, photosynthetic rate, and protective enzyme activities, as well as the yield and kernel quality of the cultivars under cadmium (Cd) stress. Applying Ca alleviated the inhibitory effects of Cd on the height growth of peanut main stem and the length growth of the branches, resulting in the increase of plant dry mass, and mitigated the Cd damage on peanut leaf, manifesting in the increase of leaf chlorophyll content, photosynthetic rate, superoxide dismutase (SOD), peroxidase (POD), and catlase (CAT) activities, and soluble protein content, and the decrease of leaf malondialdeyde (MDA) content. Under the application of Ca, both the pod yield and the kernel yield increased, mainly because of the increase of pod number per plant and of the kernel number per pod. Applying Ca also promoted the transformation of soluble sugar into fat and protein in peanut kernel, increased the kernel fat and protein contents, and improved the kernel quality under Cd stress. Ca application decreased the kernel Cd content of the cultivars, with better effect on Yuhua15 than on XB023. PMID- 22303669 TI - [Effects of no-tillage and stubble-remaining on soil enzyme activities in broadcasting rice seedlings paddy field]. AB - A field experiment was conducted to study the effects of four cultivation modes (conventional tillage, no-tillage, conventional tillage + stubble-remaining, and no-tillage + stubble-remaining) on the activities of urease, acid phosphatase, protease, and cellulose in different soil layers in a broadcasting rice seedlings paddy field. Under the four cultivation modes, the activities of test enzymes were higher in upper than in deeper soil layers, and had a greater difference between the soil layers under no-tillage + stubble-remaining. In upper soil layers, the activities of test enzymes were higher in the treatments of no tillage than in the treatments of conventional tillage, being the highest under no-tillage + stubble-remaining and the lowest under conventional tillage. In deeper soil layers, the test enzyme activities were the highest under conventional tillage + stubble-remaining, followed by no-tillage + stubble remaining, no-tillage, and conventional tillage. During the growth period of rice, soil urease and cellulose activities were lower at tillering stage, increased to the maximum at booting stage, and decreased then, soil acid phosphatase activity was higher at tillering stage but lower at elongating stage, whereas soil protease activity peaked at tillering and heading stages. PMID- 22303670 TI - [Change characteristics of soil available nitrogen and phosphorus and heavy metal contents after long-term cultivation of vegetables]. AB - Soil samples were collected from three vegetable fields under different years of cultivation in Changsha suburbs of Hunan Province, South-central China to study the accumulation characteristics, risks, and sources of soil available nitrogen and phosphorus and heavy metals in the fields. With the increasing year of vegetable cultivation, the soil NO3(-)-N, Olsen-P, and heavy metals contents in the fields increased significantly. The average contents of soil NO3(-)-N, Olsen P, and Cd in the vegetable fields having been cultivated for 1-2 years in Ningxiang County, 10-15 years in Changsha County, and 30 years in Kaifu District were 21.1, 31.9 and 0.33 mg x kg(-1), 42.0, 146.9 and 0.52 mg x kg(-1), and 49.5, 219.9 and 1.40 mg x kg(-1), respectively. The cumulative index (CI) of soil heavy metals generally followed the sequence of Cd >> Cu > Pb > Ni > Zn. Principal component analysis and cluster analysis showed that compared with soil NH4 OAc extracted potassium, pH, organic matter and NH4(+)-N, that were dominated by natural factors, the soil Olsen-P and NO3(-)-N had the similar accumulation characteristics with the soil heavy metals, being mainly controlled by fertilization. It was considered that the soil environment and health quality of the vegetable fields in Changsha suburbs were not optimistic. The longer the cultivation year of vegetables, the more the soil NO3(-)-N, Olsen-P, and heavy metals accumulated in the fields. The accumulation of these elements in the fields could be primarily due to the long-term fertilization. PMID- 22303671 TI - [Effects of biochar amendment on cropland soil bulk density, cation exchange capacity, and particulate organic matter content in the North China Plain]. AB - A 3-year field experiment with randomized block design was conducted to study the effects of biochar amendment on the soil bulk density, cation exchange capacity (CEC), and particulate organic matter C (POM-C) and N (POM-N) contents in a high yielding cropland in the North China Plain. Four treatments were installed, i.e., chemical NPK (CK), chemical NPK plus 2250 kg x hm(-2) of biochar (C1), chemical NPK plus 4500 kg x hm(-2) of biochar (C2), and 750 kg x hm(-2) of biochar-based slow release fertilizer (CN). Comparing with CK, treatments C1 and C2 significantly decreased the bulk density of 0-7.5 cm soil layer by 4.5% and 6.0%, respectively, and the treatments with biochar amendment increased the CEC in 0-15 cm soil layer, with an increment of 24.5% in treatment C2. Biochar amendment also increased the C (POM-C) and N (POM-N) contents in 0-7.5 cm soil layer, e.g., the POM-C and N contents in treatment C1 and C2 were 250% and 85%, and 260% and 120% higher than those of the CK, respectively. After three years of biochar amendment, the soil had obvious improvement in its physical and chemical properties, and played more active roles in soil carbon sequestration and greenhouse gases emission reduction. PMID- 22303672 TI - [Hyper-spectral estimation of soil organic matter content based on wavelet transformation]. AB - A total of 60 soil samples with approximate contents of N, P, and K and greatly different content of organic matter were selected by statistical analysis. Through hyper-spectral detection and analysis, the first derivative spectrum of the soil logarithmic reflectance was obtained, and was decomposed by the Bior 1.3 wavelet function. The approximative signal of the lowest frequency and the noise signal of the highest frequency were removed from the input spectrum so as to obtain the characteristic spectrum corresponding to soil physical and chemical parameters. The sensitive bands of soil organic matter were selected by correlation analysis, and the forecasting models were built by multiple regression analysis, based on the sensitive bands and the characteristic spectrum, respectively. Through comparison analysis, the optimal wavelet decomposing resolution for extracting the characteristic spectrum of soil organic matter was ascertained, and the best forecasting model was established. The best wavelet decomposing resolution was 9, followed by 8 and 10. Based on the characteristic spectrum of wavelet decomposing of 9 resolutions, the model R2 reached 0.89, which was increased by 0.31 as compared to the model based on sensitive bands, and increased by 0.10 as compared to the model based on the original spectrum. PMID- 22303673 TI - [Simulation of cropland soil moisture based on an ensemble Kalman filter]. AB - By using an ensemble Kalman filter (EnKF) to assimilate the observed soil moisture data, the modified boreal ecosystem productivity simulator (BEPS) model was adopted to simulate the dynamics of soil moisture in winter wheat root zones at Xuzhou Agro-meteorological Station, Jiangsu Province of China during the growth seasons in 2000-2004. After the assimilation of observed data, the determination coefficient, root mean square error, and average absolute error of simulated soil moisture were in the ranges of 0.626-0.943, 0.018-0.042, and 0.021 0.041, respectively, with the simulation precision improved significantly, as compared with that before assimilation, indicating the applicability of data assimilation in improving the simulation of soil moisture. The experimental results at single point showed that the errors in the forcing data and observations and the frequency and soil depth of the assimilation of observed data all had obvious effects on the simulated soil moisture. PMID- 22303674 TI - [Radiometers performance attenuation and data correction in long-term observation of total radiation and photosynthetically active radiation in typical forest ecosystems in China]. AB - Based on the total radiation and photosynthetically active radiation (PAR) observations with net radiometer (CNR1) and quantum sensor (Li-190SB) in 4 ChinaFLUX forest sites (Changbaishan, Qianyanzhou, Dinghushan, and Xishuangbanna) in 2003-2008, this paper analyzed the uncertainties and the radiometers performance changes in long-term and continuous field observation. The results showed that the 98% accuracy of the total radiation measured with CNR1 (Q(cNR1)) could satisfy the technical criterion for the sites except Xishuangbanna where the Q(CNR1) was averagely about 7% lower than Q(CM11), the radiation measured with high accuracy pyranometer CM11. For most sites, though the temperature had definite effects on the performance of CNR1, the effects were still within the allowable range of the accuracy of the instrument. Besides temperature, the seasonal fog often occurred in tropical rain forests in Xishuangbanna also had effects on the performance of CNR1. Based on the long-term variations of PAR, especially its ratio to total radiation in the 4 sites, it was found that quantum sensor (Li-190SB) had obvious performance attenuation, with the mean annual attenuation rate being about 4%. To correct the observation error caused by Li 190SB, an attempt was made to give a post-correction of the PAR observations, which could basically eliminate the quantum sensor's performance attenuation due to long-term field measurement. PMID- 22303675 TI - [Simulation of Larix gmelinii tree volume growth based on random effect]. AB - Based on the stem analysis data of 80 sample trees in dahurian larch (Larix gmelinii) plantations of Daqingchuan Forest Farm, Dailing Forest Bureau in Heilongjiang Province and the Logistic growth model, the NLME procedure of S-PLUS software was adopted to fit the nonlinear tree volume growth models, with consideration of individual tree effect and plot effect, and the evaluation statistics such as AIC, BIC, Log Likelihood, and likelihood ratio test were used to compare the prediction precisions of the models. The results showed that the random effect models with parameters b1, b2, and b3 (representing the random parameters for progressive, scale, and shape in Logistic model, respectively) had the best performance when considering individual tree effect, while the models with parameter b1 had the best performance when considering plot effect. The models considering both individual tree effect and plot effect provided better model fitting than the basic model (Logistic growth model), and the models considering individual tree effect showed more precision, as compared with those considering plot effect. The model validation indicated that random effect models not only showed the mean variation trend of individual tree volume growth, but also showed the differences among the individuals. In addition, the prediction precision of the models could be further improved through the calibration of random parameters. PMID- 22303676 TI - [Prediction of potential distribution area of Erigeron philadelphicus in China based on MaxEnt model]. AB - Erigeron philadelphicus, an alien weed originated from North America, has already invaded in Shanghai, Jiangsu, Anhui, and some other places in China, caused harm on local ecosystem and demonstrated huge potential invasiveness. By using MaxEnt model and geographic information system (GIS), this paper analyzed the environmental variables affecting the distribution of E. philadelphicus, and intuitively and quantitatively predicted its potential distribution regions in China. The prediction was verified by the ROC curve, and the results showed that E. philadelphicus had a wide potential distribution range, with the main suitable distribution area in Shanghai, Jiangsu, Zhejiang, Anhui, Henan, Hubei, Hunan and Jiangxi. At present, the actual invasive range of E. philadelphicus was far narrower than its potential maximum invasive range, and likely to be continued to spread. The ROC curve test indicated that the prediction with MaxEnt model had a higher precision, and was credible. Air temperature and precipitation could be the main environmental variables affecting the potential distribution of E. philadelphicus. More attentions should be addressed to the harmfulness of the weed. To eradicate the existing E. philadelphicus populations and to strictly monitor the invasion of E. philadelphicus to its most suitable distribution area could be the effective measures to prevent and control the further invasion of the alien weed. PMID- 22303677 TI - [Risk assessment of coastal ecosystem in Beibu Gulf, Guangxi of South China]. AB - Based on the marine ecological investigation in the coastal area of Beibu Gulf, Guangxi in September 2009, a GIS-based evaluation was conducted on the present status of ecological environment quality, including seawater quality, nutrient level, biomass, primary productivity, biodiversity, and ecological buffer capacity, in the area in autumn, and the integrated ecological risk index (ERI) was adopted to assess the risk of the coastal ecosystem in the Gulf. In September 2009, the study area had a better ecological environment quality. Most of the risk indicators were at medium or lower level, and the total area was overall at low ecological risk level. The ERI showed that there was an obvious spatial heterogeneity in the distribution of the ecological risk. The nearer to the harbors, the higher the risk was. PMID- 22303678 TI - [Integrated assessment of eco-environmental vulnerability in Pearl River Delta based on RS and GIS]. AB - Based on the remote sensing data and with the help of geographic information system, an integrated assessment was conducted on the eco-environmental vulnerability of Pearl River Delta in 2004-2008. Spatial principal component analysis was used to generate the evaluation indicators, and analytic hierarchy process (AHP) was applied to determine the weights of the evaluation factors. The reasons causing the vulnerability of the eco- environment in Pearl River Delta were discussed. In the study area, its middle part was the most vulnerable region, occupying 34.0% of the total, eastern part was the moderately vulnerable region, accounting for 25.5%, and western part was the lightly and slightly vulnerable areas, accounting for 28.7 and 11.8%, respectively. Totally, the moderately and lightly vulnerable areas occupied 54.2%, indicating that a majority of the Delta was under moderate and light vulnerability. The natural factors affecting the eco-environmental vulnerability of the Delta were altitude, heavy rain days, water and soil erosion rate, flooded infield rate, normalized difference vegetation index (ND VI) and landscape diversity index, whereas the human factors were population density, waste discharge per unit area, exhaust emission per unit area, land use change, chemical fertilization intensity, pesticide application intensity, amount of motor vehicles possessed by ten thousands people, and index of environmental protection investment. The main characteristics of the extremely and heavily vulnerable regions were low altitude, high frequency of flood disaster, large flooded infield, serious vegetation degradation, high pollution level and low environment protection investment index. PMID- 22303679 TI - [Abundance of archaea, crenarchaea and bacteria in selected agricultural soils of China]. AB - Eukaryota, bacteria and archaea are the three domains of life. As the third domain of life, archaea has been found not only in extreme environments such as high-temperature, high-saline, and extremely acid habitats, but also in moderate environments including ocean, lake and soil, which implies that archaea may contribute greatly to various ecosystems. By targeting the 16S rRNA gene with real-time PCR approaches, this paper studied the abundance of archaea, crenarchaea and bacteria from two agricultural soil profiles and two long-term fertilization stations Qiyang (QY) and Fengqiu (FQ). The 16S rRNA gene copy number of crenarchaea was 1-2 orders of magnitude lower than that of archaea, and the order of these three groups was crenarchaea < archaea < bacteria. The ratios of both archaea and crenarchaea to bacteria increased with soil depth. The abundance of archaea and crenarchaea had significantly different responses to different fertilization treatments. In QY station, the copy numbers of archaeal and bacterial 16S rRNA gene had significant positive correlations with soil pH (r = 0.850, P < 0.01 and r = 0.676, P < 0.05, respectively); in FQ station, all the 16S rRNA gene copy numbers of archaea, crenarchaea and bacteria had no significant correlations with soil pH, but significantly correlated with soil organic matter (r = 0.783, P < 0.05; r = 0. 827, P < 0.05; r = 0.767, P < 0.05, respectively). To understand the distribution of archaea and crenarchaea in agricultural soil could provide important information to evaluate their ecological functions in soil ecosystem and element cycling. PMID- 22303680 TI - [Distribution and characteristics of soil antagonistic actinomycetes on northern slope of Taibai Mountain, Qinling]. AB - Twelve representative soil samples were collected from different altitudes on the northern slope of Taibai Mountain to study the distribution and characteristics of soil antagonistic actinomyces by using agar block method. There existed a great deal of soil antagonistic actinomyces in the study area. Among the 141 actinomycete strains isolated, 116 strains (82.3%) showed antagonism toward 12 target bacteria or fungi. The antagonistic strains at altitudes 800-1845, 3488, 3655, and 3670 m occupied 73.7% -86.8%, 81.3%, 78.9% and 82.3% of the total, respectively. 42.1% of the strains at altitudes 1200-2300 m and > 3400 m showed strong and broad spectrum antagonistic activity, suggesting that there was a great potential for the isolation of actinomycete strains with strong anti-biotic capability at these altitudes. 24.1% of the antagonistic actinomycetes showed antagonism against Staphyloccocus aureu, and 2.4%, 6.9% and 11.2% of them showed activity toward Verticillium dahliae in cotton, Phytophthora sp. in strawberry and Neonectria radiciccla in ginseng, respectively. This study showed that the soil actinomycete antagonistic potentiality (SAAP) could be used as a quantitative indicator to evaluate the potential of antagonistic actinomycete resources in soil. PMID- 22303681 TI - [Characteristics of floor litter and soil arthropod community in different types ot subtropical forest in Ailao Mountain of Yunnan, Southwest China]. AB - By using line transect method, an investigation was conducted on the floor litter and soil arthropod community in a mid mountain wet evergreen broad-leaved forest, a mossy dwarf forest, and a Populus bonatii forest in Ailao Mountain of Yunnan in April (dry and hot season), June (rainy season), and December (dry and cold season), 2005. In both dry and rainy seasons, the existing floor litter mass, C storage, and C/N ratio in the three forests all increased in the order of mossy dwarf forest > P. bonatii forest > evergreen broad-leaved forest, but the N storage had less difference. In the floor litter layer of the forests, Acari and Collembola were the dominant groups of soil arthropod community, while Diptera larvae, Coleoptera, ants, and Homoptera were the common groups. The Sorenson coefficients of soil arthropod community in the three forests were extremely great. No significant differences were observed in the soil arthropod density (ind x m(-2)) in the floor litter layer among the three forests, but the relative density (ind x g(-1)) of soil arthropods was higher in the evergreen broad-leaved forest and P. bonatii forest than in the mossy dwarf forest. In the three forests, the density of soil arthropods was significantly higher in dry season than in rainy season, but the Shannon diversity index had less difference. There were significant positive correlations between the existing floor litter mass and the individual density (ind x m(-2)) and dominant groups of soil arthropod communities in dry and hot season (April), but negative correlations between the existing floor litter mass and the relative density (ind x g(-1)) of soil arthropod communities and Acari in dry and cold season (December). The individual densities of Collembola and Coleoptera also had positive correlations with the N storage of the existing floor litter mass in the three forests. It was considered that the floor litter and the development of soil arthropod community in the litter layer of the subtropical forests in Ailao Mountain had a close relation with the vegetation structure of the forests, and the individual density and the diversity of the soil arthropod community were controlled by the floor litter, whereas the environmental factors such as temperature and moisture in the forests also had obvious effects on the seasonal dynamics of the individual density of the soil arthropods. PMID- 22303682 TI - [Occurrence dynamics of migratory pest insects Cnaphalocrocis medinalis and Sogatella furcifera in transgenic Bt rice field in Xing'an County of Guangxi Province]. AB - An investigation was conducted in Xing' an County of Guangxi Province in 2010 to study the occurrence and damage characteristics of two unique migratory pest insects, rice leaffolder (Cnaphalocrocis medinalis) and white-backed planthopper (Sogatella furcifera), in a transgenic Bt rice (cv. HH1 with dual Cry1Ab+Cry1Ac genes) field, taking the corresponding non-transgenic parent (cv. MH63) field as the control. No significant differences were observed in the abundance of C. medinalis eggs and larvae in the two fields, but the percentage of fold-leaf plants and the fold-leaf rate per plant were significantly lower in transgenic Bt rice field than in the control, suggesting that transgenic Bt rice had higher resistance against the target pest insect C. medinalis. As for S. furcifera, its occurrence dynamics of nymphs, adults (including macro- and brachypterous forms), and whole population had no significant differences between the two fields, but the abundance of the nymphs and brachypterous adults at the peak stage of S. furcifera occurrence was obviously higher in transgenic Bt rice field than in the control, while the macropterous abundance was in adverse. The sex ratio of female of the macropterous adults at the late growth stage of rice was generally lower in transgenic Bt rice field than in the control. These results suggested that under the background of large area commercial production of transgenic Bt rice, the occurrence and harm of the non-target pest insect S. furcifera could become more complicated. PMID- 22303683 TI - [Toxicity and bioactivity of several alternative nematocides against Ditylenchus destructor]. AB - By the methods of fumigation and contact assay, this paper determined the toxicity of four kinds of soil fumigants and six kinds of non-fumigants against Ditylenchus destructor. In the meantime, the bioactivity of the agents was evaluated by the corrected mortality rate of D. destructor after treated with the LC50 dose of each agent for different time. The LC50 values of soil fumigants dazomet, 1, 3-dichloropropene, metham-sodium, and chloropicrin were 0.49, 0.89, 0.91, and 3.60 mg x L(-1), and those of non-fumigants emamectin benzoate, abamectin, ethoprophos, fosthiazate, aldicarb, and carbosulfan were 31.2, 48.1, 224.3, 288.4, 632.3, and 823.9 mg x L(-1), respectively. The corrected mortality rate increased with treating time. After treated with LC50 dose, the inhibitory effects of dazomet, 1,3-dichloropropene, abamectin, and emamectin benzoate kept on a higher level at the time, and the corrected mortality rate did not decline after breaking away from the treatment, but the D. destructor recovered when exposed to natural state after treated with ethoprophos and aldicarb for 48h. It was suggested that dazomet, 1,3-dichloropropene, abamectin, and emamectin benzoate were the potential alternative nematicides used for the control of D. destructor. PMID- 22303684 TI - [Control effects of Ricinus communis extracts on Meloidogyne incognita]. AB - Toxicity test and pot experiment were conducted to study the nematocidal activity and control effects of Ricinus communis extracts on Meloidogyne incognita. The results showed that both the ricinine and the R. communis water extracts had high nematocidal activity. The ricinine at concentration 2 g x L(-1) and treated for 48 hours had the strongest nematocidal activity, leading to 91.5% of corrected mortality of M. incognita and with the LC50 being 0.6 g x L(-1), whereas the R. communis water extracts at concentration 100 g x L(-1) and treated for 48 hours had the strongest nematocidal activity, which led to 83.5% of corrected mortality of M. incognita, and the LC50 was 18.3 g x L(-1). With the inoculation of M. incognita treated with ricinine, R. communis water extracts, and R. communis leaf powder, respectively, on tomato seedlings, the mean number of plant root-knots was 17.6 +/- 1.7, 20.6 +/- 1.5 and 22.8 +/- 3.7, respectively, being significantly lower than the control (37.4 +/- 2.3), and the root length increased by 46.8%, 34.5% and 33.8%, and the plant height increased by 33.5%, 22.6% and 15.8%, and the fresh mass increased by 41.4%, 18.9% and 10.1%, respectively, compared with the control. All the results suggested that R. communis extracts could mitigate the harm of M. incognita, and had obvious effects on potted tomato against M. incognita. PMID- 22303685 TI - [Genetic differentiation of Isaria farinosa populations in Anhui Province of East China]. AB - Isaria farinosa is an important entomopathogenic fungus. By using ISSR, this paper studied the genetic heterogeneity of six I. farinosa populations at different localities of Anhui Province, East China. A total of 98.5% polymorphic loci were amplified with ten polymorphic primers, but the polymorphism at population level varied greatly, within the range of 59.6%-93.2%. The genetic differentiation index (G(st)) between the populations based on Nei's genetic heterogenesis analysis was 0.3365, and the gene flow (N(m)) was 0.4931. The genetic differentiation between the populations was lower than that within the populations, suggesting that the genetic variation of I. farinosa mainly come from the interior of the populations. The UPGMA clustering based on the genetic similarities between the isolates revealed that the Xishan population was monophylectic, while the other five populations were polyphylectic, with the Yaoluoping population being the most heterogenic and the Langyashan population being the least heterogenic. No correlations were observed between the geographic distance and the genetic distance of the populations. According to the UPGMA clustering based on the genetic distance between the populations, the six populations were classified into three groups, and this classification was accorded with the clustering based on geographic environment, suggesting the effects of environmental heterogeneity on the population heterogeneity. PMID- 22303686 TI - [Genetic diversity of introduced natural enemy Agasicles hygrophila (Coleoptera: Chrysomelidae)]. AB - Flea beetle Agasicles hygrophila Selman & Vogt, the most effective natural enemy of alligator weed Alternanthera philoxeroideis, is originated from South America, and has been introduced into China for more than 20 years to control the weed. In this study, the technique of random amplification of polymorphic DNA (RAPD) was applied to assess the genetic diversity of four A. hygrophila geographic populations in Guangzhou, Chongqing, Kunming, and Fuzhou of China, and, taking the population in Florida of US as the reference, the relationships between the genetic differentiation and geographic differentiation among and within the populations were explored at molecular level. Thirteen primers that produced clear and reproducible products were selected from 111 random primers to amplify the 25 samples of the five A. hygrophila populations. The total polymorphic rate was 42.0%, and the polymorphic rate of Florida population was significantly higher than that of four China populations. The genetic differentiation among the four China populations was 25.5%. The cluster analysis by UPGMA indicated that there was a positive correlation between the genetic distance and geographic distance of different A. hygrophila geographic populations. PMID- 22303687 TI - [Spatial distribution pattern and time series dynamics of Panonychus ulmi Koch in an apple orchard of Liaoning Province, Northeast China]. AB - Panonychus ulmi Koch is one of the important pest insects of apple production in China. To clarify the spatiotemporal dynamics of P. ulmi on the apple tree crowns in an apple orchard of Liaoning, Northeast China, an investigation with random sampling was conducted on the pest mite number at each direction and each layer of the crowns in the whole growth season from May to November 2007. The spatial distribution pattern and time series dynamics of P. ulmi were analyzed by calculating the indices of aggregation and using the parameters of Iwao model. In the early and mid growth periods of apple tree, P. ulmi within whole crown fitted negative binomial distribution, presented an aggregated pattern, and its fundamental component was the group composed of several individuals that attracted each other. The aggregation intensity showed a negative fluctuation with population density, namely, high population density but low patchiness density, and low population density but high patchiness density, and there existed definite differences at different crown directions and layers, i. e., the patchiness density was the highest in south direction and the lowest in west direction, and was higher in mid and lower layers than in upper layer, and in inner layer than in outer layer. PMID- 22303688 TI - [Research progress in seegrass seed dormancy, germination, and seedling growth and related affecting factors]. AB - Seagrass bed is the main primary producer in coastal areas, having highly ecological and economical values, and being one of the most important shallow marine ecosystems. This paper reviewed the research progress in the seed dormancy, germination, and seedling growth of seagrass and related affecting factors, summarized the seed dormancy modes and durations and their affecting factors, and discussed the effects of water salinity, temperature, transparency, hormone, dissolved oxygen, and population structure on the seed germination and the seedling survival and growth. Some issues in related researches and several research directions in the future were prospected. PMID- 22303689 TI - [Multiple functions-targeted algorithms and potential applications of forest simulation optimization system (FSOS)]. AB - Forest Simulation and Optimization System (FSOS) model has been widely used in British Columbia of Canada and in Changbai Mountains of China. This model is based on the viewpoint of harmonized and balanced management of forest resources and the application of simulated annealing optimized algorithms in arranging forest management schemes, aimed to realize the sustainable and harmonized development of forest resources multiple objective management and to transform forests to their desired status. The multiple functions (or the multiple objectives) in the FSOS model include water storage and purification, carbon sequestration, wildlife habitat protection, biodiversity conservation, visual landscape quality, and timber production, and the desired forest status is comprehensively defined by experts, environmental organizations, and government policies. This paper introduced in detail the simulated annealing algorithms in FSOS, including solution representation, evaluations, and transitions, and the potential applications of the algorithms in forest ecosystem planning, aimed to provide helps to the planning and management of forest resources and to the governments to quantify, analyze, and manage the forest resources, effectively monitor forest operations, and achieve the sustainable development of forest ecosystem. PMID- 22303690 TI - [Baseflow separation methods in hydrological process research: a review]. AB - Baseflow separation research is regarded as one of the most important and difficult issues in hydrology and ecohydrology, but lacked of unified standards in the concepts and methods. This paper introduced the theories of baseflow separation based on the definitions of baseflow components, and analyzed the development course of different baseflow separation methods. Among the methods developed, graph separation method is simple and applicable but arbitrary, balance method accords with hydrological mechanism but is difficult in application, whereas time series separation method and isotopic method can overcome the subjective and arbitrary defects caused by graph separation method, and thus can obtain the baseflow procedure quickly and efficiently. In recent years, hydrological modeling, digital filtering, and isotopic method are the main methods used for baseflow separation. PMID- 22303691 TI - [Effects of temperature and salinity on oxygen consumption rate and asphyxiation point of Sagitta crassa]. AB - A laboratory test was conducted to study the effects of different temperature and salinity on the oxygen consumption rate and asphyxiation point of chaetognath Sagitta crassa. Both temperature and salinity had significant effects on the oxygen consumption rate (IO) and specific oxygen consumption rate (SO) of S. crassa. When the temperature raised from 5 degrees C to 25 degrees C, the IO and SO of S. crassa increased first, and then presented an obvious decreasing trend, with the regression function being y = 0.0058x3-0.2956x2 +4.415x-8.7816 (R2 = 0.99, P < 0.05) for IO and y = 0.0011x3-0.0546x2+0.8161x-1.6232 (R2 = 0.99, P < 0.05) for SO. The IO and SO at different temperature were in the ranges of 6.30 11.71 microg x ind(-1) x h(-1) and 1.22-2.16 microg x mg(-1) x h(-1), respectively, and the asphyxiation point was 4.18-6.87 mg x L(-1). When the salinity increased from 10 to 40, the IO and SO of S. crassa decreased gradually, with the regression function being y = -0.0068x2-0.1412x+21.702 (R2 = 0.89, P < 0.05) for IO and y = -0.0013x2 -0.0261x+ 4.0114 (R2 = 0.89, P < 0.05) for SO. The IO and SO at different salinity were in the ranges of 4.98-17.73 microg x ind(-1) x h(-1) and 0.92-3.56 microg x mg(-1) x h(-1), respectively, and the asphyxiation point was 4.02-6.24 mg x L(-1). Based on the differences in the oxygen consumption rate and asphyxiation point between S. crassa and other aquatic animals, it was concluded that S. crassa was a stenooxybiotic zooplankton species. PMID- 22303692 TI - [Clinical findings of a group of children with auditory neuropathy spectrum disorder]. AB - OBJECTIVE: In order to extend the knowledge of auditory neuropathy spectrum disorder (ANSD), the clinical data of a group of infants and young children with this disorder was reported. METHOD: This retrospective study involved 84 cases (151 ears). The subjects aged from 2 months to 6 years old. Descriptive analysis was carried out on case history, audiological and imaging results and the outcome of cochlear implantation. RESULT: There were a variety of case history, including 11 of hyperbilirubinemia, 2 of family history of deafness, 3 of hypoxia, 1 of prematurity, 1 of nuclei basales pathology, 2 of congenital atelencephalia,and 13 of cochlear nerve deficiency (CND). The audiological results varied too. Click ABR ranged from no response at the maximum output level to Wave V thresholds as low as 70 dB nHL. Behavioral thresholds were mild in 1, moderate in 2 and profound in 20. The inner ear MRI were normal in 16 cases, CND in 12 and CND accompanied by periventricular leukomalacia in 1. 5 cases were implanted in the affected ear. The results in 3 were comparable with that of cochlear loss, 1 were less effective than that of cochlear loss, 1 became none user of the device. CONCLUSION: ANSD is a heterogeneous group with a wide variety on case history, audiological and imaging results and the outcome of cochlear implant. Therefore, comprehensive clinical examinations are necessary so that individualized intervention program can be made. PMID- 22303693 TI - [Audiometric configuration distribution of hearing loss in a clinical population]. AB - OBJECTIVE: Audiometric configuration distribution of hearing loss was analyzed for public policy efforts of hearing loss prevention and rehabilitation. METHOD: According to the archived records of the Clinical Audiology Center of Beijing Tongren Hospital, Capital Medical University, audiometric configuration distribution was analyzed by different type,degree of hearing loss and age factor. RESULT: 1. Overall audiometric configuration distribution: the percentages of "sloping", "rising", "flat", "U-shaped", and other type of audiometric configuration distributions are 52.8%, 7.6%, 15.4%, 13.2% and 11.0%, respectively. No difference was found between male and female in the audiometric configuration distribution; 2. Audiometric configuration distribution by type of hearing loss: sloping hearing loss dominants sensorineural and mixed hearing loss; 3. Audiometric configuration distribution by degree of hearing loss: sloping hearing loss dominants mild, moderate and severe hearing loss, U-shaped hearing loss dominants profound hearing loss; 4. Audiometric configuration distribution by age: for age group 5 to 7, the highest prevalence of audiometric configuration is "sloping", followed by "flat", "U-shaped", other type and "rising"; with the age increasing, the percentage of sloping hearing loss increased dramatically. CONCLUSION: Audiometric configuration distribution shows obvious characteristic of on the type, degree of hearing loss and age factor. "sloping" hearing loss dominates the audiometric configuration. PMID- 22303694 TI - [The expression and significance of IGF-1R in nasal polyp and its relationship with allergic rhinitis]. AB - OBJECTIVE: To study the expression of insulin-like growth factor-1 receptor(IGF 1R) in nasal polyps and its relationship with allergic rhinitis. METHOD: The mRNA and protein expression of IGF-1R in 40 cases (20 cases with allergic rhinitis and 20 cases without) nasal polyps tissue (the CRSWNP group) and 20 middle turbinate tissue samples (the control group) were examined by fluorescence quantitative polymerase chain reaction (FQ-PCR) and immunohistochemistry. RESULT: The positive staining rate of IGF-1R protein of nasal polyps tissue is 70.8% and that of control is 12.3%, the expression of IGF-1R mRNA of nasal polyp is 0.748 +/- 0.111,which is significant higher than that of the control group is 0.107 +/- 0.208 (P < 0.01). No significant difference of the expression of IGF-1R mRNA between with and without allergic rhinitis cases and between with and without endoscopy sinus surgery history cases in the CRSWNP group. CONCLUSION: The overexpression of IGF-1R maybe play important roles in the formation of nasal polyp. Hypersensitivity reaction type I mediated by IgE has no contribution to the overexpression of the IGF-1R. PMID- 22303695 TI - [The effect of reversal steps stapedotomy on the treatment of otosclerosis]. AB - OBJECTIVE: To determine the efficacy of reversal steps stapedotomy in the treatment of otosclerosis. METHOD: From January 2006 to December 2009, a total of 70 patients (81 ears) with otosclerosis who underwent stapedotomy were retrospectively evaluated. Among these 81 ears, 41 ears underwent classical stapedotomy and 40 ears underwent reversal steps stapedotomy. We compared the postoperative results of pure tone tes , the intraoperative complications of stapes and incus and the incidence rate of postoperative vertigo after surgery between the two groups. RESULT: The rate of postoperative air bone gap < or = 20 dB was 70.7% in the classical stapedotomy group and was 80.0% in reversal steps stapedotomy group. There were no significant differences between the two groups (P =0.181). The reversal steps stapedotomy group seem to had less complications of stapes and incus. The incidence rate of postoperative vertigo in reversal steps stapedotomy group significantly lower than in classical stapedotomy group (P = 0.037). CONCLUSION: Reversal steps stapedotomy can effectively improve the hearing of patients with otosclerosis and can reduce the complications of stapedotomy. PMID- 22303696 TI - [Treatment of infection in posterior tympani cavity during surgical procedures of otitis media]. AB - OBJECTIVE: Analyse the effect of the treatment of infection in posterior tympani cavity in 168 cases with chronic otitis media. METHOD: Infection was eliminated in posterior tympani cavity of all 168 cases after surgical procedures of otitis media, and 102 tympanoplasty with autoplastic bone were operated in all cases. 22 tympanoplasty were operated without mastoidectomy, 53 with transmastoid approach, 27 with mastoidectomy and tympanoplasty. RESULT: All cases were followed up for more than one year. 160 cases were cured, the effective rate was 95% and no recurrence appeared except for 8 cases. The average threshold of hearing improvement of 87 cases > 15 dB, the effective rate was 85%. CONCLUSION: To eliminate infection, the exploratory surgery of posterior tympani cavity should be done during surgical procedures of otitis media, for improving the effect of the treatment of otitis media. PMID- 22303697 TI - [Diagnosis and surgical operation for fourth branchial cleft anomalies]. AB - OBJECTIVE: To explore diagnosis and surgical operation through analyzing clinical features of the fourth branchial cleft anomalies. METHOD: Clinical materials of 10 patients with the fourth branchial cleft anomalies were retrospectively analyzed, and literatures were studied to explore the diagnosis, differential diagnosis and treatment methods of surgical operation; lesions of 10 patients were completely removed by surgical operation, and internal sinus was properly handled. RESULT: All 10 cases were cured, no recurrence were observed during a follow-up of 1-3 years. 1 patient appeared low voice, and drinking cough, back to normality after 2 weeks; 1 patient appeared paralysis of left hypoglossal nerves, back to normality after 3 months. CONCLUSION: Recurrent deep neck abscess and chronic sinus infections of anterior area in the lower part of neck should be considered with the diagnosis of the fourth branchial cleft anomalies. Enhanced neck CT scan and barium sulfate meal examination aid to diagnosis, pathological examination can be confirmed. Complete surgical removal of lesions is an effective treatment of fourth branchial cleft anomalies, knowing of the courses of internal sinus and spread of infection, and use of principle of selective neck dissection is the key to ensure complete removal of lesions. PMID- 22303698 TI - [Assessment of cochlear implant performance with Mandarin Hearing In Noise Test]. AB - OBJECTIVE: To evaluate the abilities speech perception of post-lingual cochlear implant patients by Mandarin Hearing In Noise Test(MHINT), get the performance intensity function (P-I function). METHOD: The material was MHINT adults' version, including 12 lists, 20 sentences per list. Twenty-two cochlear implant patients were the subjects, age from 14 to 56. Three adaptive rules were used during the test. Firstly Rule 3 would be done. If subject could finish the test, then Rule 2 and Rule 1 would be used. Got the Reception threshold of sentences and speech recognition score of subjects, then got performance-intensity function (PI function). RESULT: Among those 22 subjects, 5 of them could be tested in all three rules, 3 could be tested in Rule 2 and Rule 3, 7 of them could be tested with Rule 3, and 7 of the CI users could not be tested even with Rule 3. All of the PI functions for CI users are shifted 10 dB or more above the normal PI functions. Most CI users thought that MHINT was hard for them. CONCLUSION: When use new adaptive scoring rules for MHINT, most CI users could be tested with the modified HINT scoring rules, although three subjects could not be tested. Compared with normal hearing subjects, all CI users required positive S/N ratios to perform the HINT measures. PMID- 22303699 TI - [To observe postoperative analgesia and preemptive analgesia of Tramadol hydrochloride sustained release tablets for nasal endoscopic operation]. AB - OBJECTIVE: To observe postoperative analgesia and preemptive analgesia of Tramadol hydrochloride sustained release tablets for nasal endoscopic operation. METHOD: A total of 188 patients undergoing nasal endoscopic operation were randomized into the experimental group and control group, with 94 patients in each group. Each patient in experimental group was gaved on Tramadol hydrochloride sustained release tablets at 12h, 24h, 48h, postoperation and before the cleaning up procession respectively, the control group was not administered. VAS scores were observed at 12, 24, and 48 hours after operation. The discomfort reaction during postoperation and cleaning up procession such as insomnia, impatien, nervous, frightening, syncope and shock were also observed and recorded. RESULT: Visuala analogue scale scores of the experimental groups after 12, 24 hours and 48h were significantly lower than the control group. The discomfort reaction appear more frequently in control group. CONCLUSION: Tramadol hydrochloride sustained release tablets effectively relieves postoperative pain of nasal endoscopic operation. It can also decrease the discomfort reaction during postoperation and cleaning up procession and facilitate recovering of patients. PMID- 22303700 TI - [The expression of MMP-2, -9 in the uterine leiomyoma and its significance in prognosis]. AB - OBJECTIVE: To study on the expression and significance of MMP-2 and MMP-9 in the nasus epithelial carcinoma and their signification. METHOD: Fifty cases of epithelial carcinoma tissue and 50 cases of normal nasus tissue were detected for MMP-2 and 9 by immunohistochemistry technique (SP), and analysed their relationships between expression of MMP-and some clinical symptoms. RESULT: The positive ratio of expression of MMP-2 in 50 cases of epithelial carcinoma was 52.0% (26/50), which was significantly higher than those in the normal nasus tissue 28.0% (14/50), P < 0.05. The positive ratio of expression of MMP-9 in 50 cases of epithelial carcinoma was 58.0% (29/50), which was significantly higher than those in the normal nasus tissue 10.0% (5/50), P < 0.05. CONCLUSION: It was suggested that there was a close relationship between pathogenesis and development of nasus epithelial carcinoma and the expression of MMP-2, MMP-9 in the epithelial carcinoma tissues. The positive results of MMP-2, MMP-9 is partly valid for diagnosis of prognosis rate of MMP-2 and MMP-9 expression was high in nasus epithelial carcinoma tissues, MMP-2 and MMP-9 expression levels might be able to provide prognostic information. PMID- 22303701 TI - [Study of protective effects on noise-induced hearing loss using N-acetyl cysteine]. AB - OBJECTIVE: To evaluate the protective effects of oral administration of N-acetyl cysteine (NAC) on noise-induced hearing loss. METHOD: Three hundred sixty three volunteers were recruited and randomly divided into two groups: experimental group (n=223) and control group (n=140). The subjects had received oral administration of NAC in the experimental group and placebo in the control group before noise exposure. The routine audiometric evaluation and ABR testing were performed and recorded pre- and post-noise exposure. The statistical analysis was carried out on the data obtained from two groups with SPSS 11.0. RESULT: The hearings of all the participatory were changed after noise exposure, but there were statistically significant differences between two groups. CONCLUSION: The protective effects of NAC were prominent on the noise-induced hearing loss. PMID- 22303702 TI - [Thirty years' retrospection of integrative medicine studies]. PMID- 22303703 TI - [Quick recovery: the core concept of the peri-operative integrative medicine studies]. AB - The author raised that the orientation of peri-operative integrative medicine studies as: Correct surgical decision-making is the prerequisite for successful surgery, the skilled surgical technique is the key for successful operation. At the same time, considerate and appropriate peri-operative management is the guarantee for the success of surgery. Consequently, quick recovery is the core concept of peri-operative integrative medicine studies. Its academic value and practical significance lie in that it can accelerate the improvement of surgical skills, optimize various effective measures to improve the overall efficacy, promote discipline construction and personnel training to improve academic levels, promote the development of Chinese medicine and accelerate its internationalization. PMID- 22303704 TI - [Clinical observation of the low molecular weight heparin calcium combined with Yinxing Damo injection on the prevention of deep venous thrombosis after the operation of intertrochanteric fracture]. AB - OBJECTIVE: To observe the therapeutic effect of the low molecular weight heparin calcium (LMWHC) combined with Yinxin Damo Injection (YDI) on the prevention of deep venous thrombosis (DVT) after the operation of intertrochanteric fracture. METHODS: Sixty-two patients with intertrochanteric fracture were randomly assigned to the control group and the combined group, 31 in each group. Patients in the control group were subcutaneously injected with 6 000 IU LMWHC, twice daily. On this basis of the aforesaid treatment, patients in the combined group were intravenously dripped with YDI at the daily dose of 20 mL, once daily. The treatment lasted for 10 days in both groups. The DVT incidence rate, postoperative drainage amount of blood, activated partial thromboplastin time (APTT), plasma prothrombin time (PT), platelet count, and the maximal swelling rate of lower limbs after surgery were compared between the two groups after operation. RESULTS: In the control group DVT occurred in 5 cases (16. 1%) while it occurred in 2 cases (6.5%) in the combined group, showing significant differences (P < 0.05). Both APTT and PT were shortened in the two groups on the 2nd day after medication (P < 0.01). Compared with the control group, it was more obvious in the combined group, showing statistical significance (P < 0.05). Both APTT and PT were shortened in the control group on the 10th day after medication when compared with before treatment (P < 0.01). But they were postponed in the combined group when compared with before medication, showing statistical difference when compared with the control group (P < 0.05). The platelet count increased in the combined group on the 10th day after medication. Besides, it was higher than that in the control group, showing statistical difference (P < 0.05). The platelet counts were in the normal range. CONCLUSIONS: LMWSC combined with YDI could not only reduce the incidence of DVT after the operation of intertrochanteric fracture, but also change the state of higher blood coagulation. It showed significant effect on preventing DVT after the operation of intertrochanteric fractures. PMID- 22303705 TI - [Clinical study of Shenfu injection on the post-operative cognitive dysfunction in senile patients receiving the orthopedic surgeries after general anesthesia]. AB - OBJECTIVE: To study the effect of Shenfu Injection (SI) on the post-operative cognitive dysfunction in senile patients receiving the orthopedic surgeries after general anesthesia. METHODS: 100 patients, 60-89 years old, waiting for selective surgery at the orthopedics department, were randomly assigned to two groups, the SI group (50 cases) and the control group (50 cases), who met the standard of the American Society of Anesthesiologists (ASA) II-III. After surgical incision, patients in the SI group were transfused with SI 200 mL (50 mL SI was added in 200 mL normal saline), while those in the control group were transfused with 200 mL normal saline at the same time. The mean arterial pressure (MAP), heart rate (HR), and oxygen saturation (SpO2) were compared between the two groups before anesthesia, after intubation, 30 min and 60 min after anesthesia, 5 min and 30 min after extubation. The time for surgery, the time of intra-operative hypotension, the volume of hemorrhage, the time for post-operative consciousness recovery, the liver function, the kidney function, and the fasting blood glucose of patients before surgery, 3 days and 7 days after operation were compared. The cognitive functions of patients were tested before surgery, 3 days and 7 days after operation. The incidence of post-operative cognitive dysfunction of patients was compared between the two groups. RESULTS: There was insignificant difference in MAP, HR, and SpO2 between the two groups at each time point (P > 0.05). There was insignificant difference in the pre-operative cognitive function score, the time for surgery, the time of intra-operative hypotension, the volume of hemorrhage, the liver function, the kidney function, and the fasting blood glucose between the two groups ( P > 0.05). The time for post-operative consciousness recovery was obviously shorter in the SI group than in the control group, showing significant difference (P < 0.05). The post-operative 3-day and 7 day cognitive function scores were obviously better in the SI group than in the control group, showing significant difference (P < 0.05). The incidence of post operative cognitive dysfunction of the SI group [3 days: 12% (6 cases); 7 days: 8% (4 cases) ] was significantly lower than that of the control group [3 days: 20% (10 cases); 7 days: 14% (7 cases) ] ( P < 0.05). CONCLUSION: SI could improve the post-operative cognitive function of senile patients receiving the orthopedic surgeries after general anesthesia, lower the incidence of post-operative cognitive dysfunction rate, and shorten the time for post-operative consciousness recovery. PMID- 22303706 TI - [Effect of Shenfu injection on the erythrocyte immune function of patients undergoing cardiopulmonary bypass]. AB - OBJECTIVE: To observe the effect of Shenfu Injection (SFI) on erythrocyte immunity function of patients undergoing cardiopulmonary bypass (CPB). METHODS: Twenty patients scheduled for valve replacement were randomly assigned to two groups, i.e. , the SFI group and the control group, 10 in each. SFI 1 mL/kg was intravenously dripped before induction of anesthesia and SFI 1 mL/kg administered in priming solution in the SFI group, while only normal saline was given to those in the control group. Venous blood samples (5 mL) were collected before induction of anesthesia (T1), 30 min CPB (T2), immediate by the end of CPB (T3), and postoperative 24 h (T4) respectively in all groups. The levels of the rosette rate of RBC-C3b receptor (RBC-C3bRR), the rosette rate of RBC-immune complex (RBC ICR), plasma malondialdehyde (MDA), free hemoglobin (FHB), and interleukin-6 (IL 6) were detected. RESULTS: There was no significant difference in the levels of RBC-C3bRR, RBC-ICR, plasma MDA, FHB, and IL-6 at T1 in both groups (P > 0.05). RBC-C3bRR at the rest time points was lower in the two groups than before induction of anesthesia. There was no statistical difference in FHB or IL-6 between T4 and T1 in the SFI group. The levels of RBC-ICR, MDA, FHB, and IL-6 increased in the two groups more than before induction of anesthesia at T2-4 ( P < 0.05). Besides, the RBC-C3b RR was lower, and levels of RBC-ICR, MDA, FHB, and IL-6 higher in the control group than in the SFI group, showing significant difference (P <0.05). CONCLUSION: SFI could decrease the generation of inflammatory mediators during CPB, improve the erythrocyte immune function of patients during CPB, and reduce the risk of postoperative infection. PMID- 22303707 TI - [Effects of unblocking meridians and Du-channel massage combined with rehabilitation training on the motor function improvement of cerebral ischemic stroke patients]. AB - OBJECTIVE: To study effects of unblocking meridians and Du-channel massage combined with rehabilitation training on the motor function improvement of cerebral ischemic stroke (CIS) patients. METHODS: Eighty CIS patients were assigned to the treatment group (40 cases) and the control group (40 cases) using random digit table method. Bobath technique was mainly carried out in patients in the control group. On the basis of routine rehabilitation training, unblocking meridians and Du-channel massage was additionally given to patients in the treatment group. The therapeutic course for all patients was 8 weeks. The changes of Fugl-Meyer Assessment-L (FMA-L), 10 meter maximal walking speed (MWS), and gait space and time parameters were compared before and after treatment. RESULTS: Before treatment there was no significant difference in each index between the two groups (P > 0.05). After treatment there was significant difference in these indices between the two groups (P < 0.05), with better results obtained in the treatment group (P < 0.01, P < 0.05). CONCLUSION: The unblocking meridians and Du channel massage could improve the motor function and walking capability of CIS patients, which was worthy of further summaries. PMID- 22303708 TI - [Efficacy observation of combination of Lumbrukinase Capsule and Probucol Tablet in treating cerebral infarction patients' unstable atheromatous plaque of the carotid artery]. AB - OBJECTIVE: To observe the effects of combination of Lumbrukinase Capsule (LC) and Probucol Tablet (PT) in treating cerebral infarction (CI) patients' unstable atheromatous plaque of the carotid artery. METHODS: 150 patients were randomly assigned to the PT group and the LC group, 75 cases in each. Patients in the PT group took 0.5 g PT each time, twice daily. On the basis of PT, patients in the LC group also took 600 thousand U LC, thrice daily. The treatment course was 12 months for all. The serum levels of TC, TG, HDL-C, LDL-C, fibrinogen (FIB), and changes of the carotid atherosclerotic plaque were measured before treatment, 6 and 12 months after treatment. Meanwhile, adverse events were recorded. RESULTS: The serum levels of TC, TG, and LDL-C were all lower 6 months after treatment than before treatment in the two groups, showing statistical significance (P < 0.05). The serum level of HDL-C was higher 6 months after treatment than before treatment in the two groups, showing no statistical significance (P > 0.05). When compared with before treatment in the same group, the serum level of FIB significantly decreased after treatment. Besides, there was statistical difference between the two groups (P < 0.05). There was no statistical difference in the serum levels of blood lipids or FIB between 12-month treatment and 6-month treatment in the same group (P > 0.05). The plaque effective rate in the LC group was superior to that of the PT group, showing statistical significance (P < 0.01). During the treatment period, the occurrence of cerebrovascular event was lower in the LC group than in the PT group (P < 0.05). Partial patients in the two groups had gastric discomfort. CONCLUSIONS: The combination of LC and PT could prevent and treat arteriosclerosis, stabilize the plaque, effectively lower the occurrence of ischemic events. Its clinical application did not increase the risk of hemorrhage. It was safe and effective, worthy of spreading. It was necessary to further observe whether combination of LC and PT could increase side effects of the digestive tract. PMID- 22303709 TI - [Retrospective analysis of risk factors in 900 patients with ischemic cerebral stroke of wind-phlegm collateral obstruction syndrome and qi deficiency blood stasis syndrome in Wuhan District]. AB - OBJECTIVE: To analyze the correlation between risk factors and ischemic cerebral stroke of wind-phlegm collateral obstruction syndrome and qi deficiency blood stasis syndrome. METHODS: Totally 900 patients of the two syndrome types were recruited. Risk factors correlated to ischemic cerebral stroke such as gender, age, time of onset, site of infarction, tongue proper, tongue fur, pulse picture, hypertension, diabetes, past stroke history, hyperlipidemia, hematocrit, smoking, drinking, genetic factor, blood type, complications were analyzed using Chi square test and non-conditional Logistic regression analysis. RESULTS: Statistical significance existed between the two syndrome types in age (X2 = 8.2392, P = 0.0413), hyperlipidemia (X2 = 4.8386, P = 0.0278), tongue proper (X2 = 7.9470, P = 0.0048), and tongue fur (X2 = 4.3298, P = 0.0375). Statistical significance existed between the two syndrome types in hyperlipidemia, tongue proper, and tongue fur, and their OR value was 0.699 (P = 0.0282), 0.332 (P =0.0071), and 0.667 (P = 0.0382) respectively. The OR value of the past stroke history was 3.226 (P = 0.0314), that of complications 0.203 (P = 0.0705), and that of anterior circulation infarction 0.214 (P = 0.0098). CONCLUSIONS: Among different ages groups, the constituent ratio of qi deficiency blood stasis syndrome was obviously higher than that of wind-phlegm collateral obstruction syndrome. Besides, patients of qi deficiency blood stasis syndrome were liable to suffer from hyperlipidemia, anterior circulation infarction, and complications. The age, blood lipid levels, site of infarction, complications are closely correlated with Chinese syndrome types of ischemic cerebral stroke, which can provide objective indices for typing ischemic cerebral stroke. PMID- 22303710 TI - [Effects of Radix Astragali on IL-1beta, TNF-alpha and antigen expression of peripheral blood mononuclear cells in patients with Graves disease]. AB - OBJECTIVE: To study the effects of Radix Astragali on serum cytokines IL-1beta, TNFalpha and antigen expression of peripheral blood mononuclear cells (PBMCs) in patients with Graves disease (GD). METHODS: Eighty GD patients at their first visit were randomly assigned to the methimazole (MMI) group (Group A) and the MMI combined Radix Astragali group (Group B), 40 in each. The improvement of clinical symptoms and thyroid functions were observed after one-month treatment. The serum IL-1beta and TNF-alpha levels in the peripheral blood were determined using radioimmunoassay. The expression levels of surface antigen CD80, CD54, and HLA-DR of PBMCs were detected using flow cytometry. RESULTS: The improvement of the thyroid gland function was similar in the two groups. There was no obvious change in the levels of autoantibody TGAb or TPOAb of the two groups. Symptoms such as fear of heat, hidrosis, palpitation, and so on were more obviously improved in Group B than in Group A (P < 0.05). The serum IL-betaP, TNFalphaa, CD00 levels in the peripheral blood were all improved in the two groups after treatment when compared with before treatment ( P < 0.05 or P < 0.01). But the serum levels of IL-beta and TNFalpha decreased more obviously in Group B than in Group A ( P < 0.05). The expression of CD54 decreased more obviously in Group B (P < 0.01), showing statistical difference when compared with Group A at the same time point (P < 0.05). CONCLUSION: Radix Astragali could significantly relieve the clinical symptoms such as hidrosis and palpitation, regulate the immune function of GD patients, playing an important role in the adjuvant therapy for GD. PMID- 22303711 TI - [Study on the functions of peripheral dendritic cells in chronic hepatitis B virus infection patients of Gan-depression Pi-deficiency syndrome and Gan-Dan damp-heat syndrome under different immune states]. AB - OBJECTIVE: To observe the functions of peripheral dendritic cells (DCs) in chronic hepatitis B virus (HBV) infection patients of Gan-depression Pi deficiency syndrome (GPS) and Gan-Dan damp-heat syndrome (GDS) under different immune states, thus to study the features of the immune expressions of the two syndromes in chronic HBV infection, providing objective evidence for Chinese medicine syndrome typing. METHODS: The 40 chronic HBV patients were randomly assigned to two groups according to the immune state. Of them, there were 20 chronic HBV patients (under the condition of immune clearance; consisting of 10 patients of GPS and 10 of GDS) and 20 chronic HBV carriers (under the condition of immune tolerance; consisting of 10 patients of GPS and 10 of GDS). Besides, 10 healthy graduate volunteers of Hunan University of Traditional Chinese Medicine were recruited as the healthy control group. Their peripheral blood mononuclear cells (PBMCs) were cultured in vitro. The exterior morphological features and ultrastructure were observed by inverted microscope and electron microscope. The expressions of HLA-DR, CD80, CD86, and CDIa of the DCs surface were detected. The secretory levels of IL-12 in the supernate of DCs were detected by ELISA reagent kit. The proliferation capacities of allogeneic mixed lymphocyte were detected using MTT. The function features of DCs in the chronic HBV patients of two syndrome types under different immune states were compared, thus analyzing the difference of each index between the two syndrome types. RESULTS: Compared with the healthy control group, the expression rates of CD86, CD80, and HLA-DR decreased in the HBV carriers group (of the two syndrome types), showing statistical difference (P < 0.05). The expression rate of CD80 decreased in the HBV group (of the two syndrome types), showing statistical difference (P < 0.05). The expression rates of CD86 and HLA-DR were lower in the GPS group than in the GDS group. The expression rate of CD80 was lower in the GPS group than in the GDS group, showing statistical difference (P < 0.05). The proliferation capacities of IL-12 and T lymphocytes were lower in the HBV patients group than in the healthy control group (P < 0.05). The proliferation capacities of IL-12 and T lymphocytes were lower in the GPS group than in the GDS group, showing statistical difference (P < 0.05). CONCLUSIONS: The functions of peripheral DCs in chronic HBV infection of patients of the GPS and the GDS under different immune states were different. The phenotype and function tests of DCs provided objective evidence for Chinese syndrome typing of chronic hepatitis B, thus reflecting the features of immune expressions of the two syndrome types and the immunology connotation. PMID- 22303712 TI - [Clinical observation of Shen No. 9 Recipe with Qingre Moshen Granule on the treatment of idiopathic membranous nephropathy after treated by multiple Western drugs with no efficacy]. AB - OBJECTIVE: To observe the clinical efficacy of Shen No. 9 Recipe (SR) combined with Qingre Moshen Granule (QMG) in treatment of idiopathic membranous nephropathy (IMN) patients with no efficacy after treated by hormone or immunosuppressive agent, and further to explore the possible mechanism of this method in treatment of IMN by detecting the cellular immune function and cytokine interleukin-2 (IL-2). METHODS: Forty-four IMN patients with no efficacy after treated by multiple Western drugs were recruited from October 2007 to October 2009. They took SR (one dosage daily, oral administration in two portions) and QMG (each package each time, thrice daily) for 24 weeks. The 24-h urine protein, glomerular filtration rate (GFR), plasma albumin (Alb), serum creatinine (SCr), urea nitrogen (BUN), triglyceride (TG), serum total cholesterol (TC), levels of cellular immune function (CD4+, CD8+, CD4+/CD8+ ratio), and IL-2 were detected before and after treatment. The changes of Chinese medicine syndrome and adverse reactions were observed and recorded. RESULTS: After treatment the complete remission rate, the basic remission rate, and the total effective rate was 4.5%, 68.2%, 84.1%, respectively. The total markedly-effective rate of Chinese medicine syndrome was 90.9%. The Chinese medicine syndrome was significantly lower than before treatment (P < 0.01). The 24-h urine protein obviously decreased (P < 0.01), Alb obviously increased (P < 0.01), levels of TC and TG obviously decreased (P < 0.01, P < 0.05). There was no obvious change in levels of SCr and BUN (P > 0.05). The GFR significantly increased (P < 0.05). CD4+ and the ratio of CD4+/CD8+ were obviously elevated (P < 0.01) and the CD8+ obviously decreased (P < 0.01). The expression level of IL-2 obviously increased, but it still was lower than the normal value, showing statistical difference (P < 0.01). CONCLUSIONS: SR + QMG showed definite efficacy in treatment of IMN patients with no efficacy after treated by multiple Western drugs. It could improve the level of cellular immunity and improve abnormal expression levels of IL-2. PMID- 22303713 TI - [Effect of electroacupuncture on the cognitive function and plasma antibodies against beta-amyloid protein in aged rats with ketamine anesthesia]. AB - OBJECTIVE: To study the effects of electroacupuncture (EA) on the changes of behavior after ketamine anesthesia, and changes of serum antibodies against beta amyloid (Abeta) and Abeta protein in the hippocampus of aged rats, thus exploring the effects of EA on the cognitive dysfunction. METHODS: Thirty 14-month old SD rats were randomly divided into 3 groups, i. e. , the control group (Group A), the ketamine anesthesia group (Group B), and the EA+ketamine anesthesia group (Group C), 10 in each group. 50 mg/kg katemine was intraperitoneally injected to rats in Group B and Group C, once daily for 7 successive days. EA was performed to rats in Group C from the 1st day of the experiment after rats awoke completely from anesthesia, twice daily for 7 successive days. Changes of the ratio of the swim time in the original platform quadrant to the total swim time and the escape latency phase were observed by Morris water maze. The peripheral blood was withdrawn by the end of the experiment. Serum anti-Abeta antibody contents were detected using enzyme-linked immunosorbent assay (ELISA). The expressions of Abeta in the hippocampus were detected using Westen blot. RESULTS: Long-term application of ketamine could lower aged rats' cognitive function. In the navigation test, the escape latency phase of rats in Group B was significantly prolonged ( P < 0.01) . On the 7th day of the experiment, the serum level of anti Abeta antibodies was lower in Group B than in Group A (P < 0.05), while the serum level of anti-Abeta antibodies was significantly higher in Group C than in Group B (P < 0.01). On the 7th day of the experiment, the expression of Abeta in the hippocampus was higher in Group B than in Group A (P < 0.05). CONCLUSION: EA could increase the contents of anti-Abeta antibodies in aged rats with ketamine anesthesia, decrease the expression of Abeta in the hippocampus, alleviate the deposition of Abeta, thus improving rats' cognitive dysfunction. PMID- 22303714 TI - [Effect of mild hypothermia in combination of acupuncture on Bcl-2 and Bax protein expressions of local cerebral ischemia/reperfusion rats]. AB - OBJECTIVE: To observe and compare the effects of acupuncture in combination of mild hypothermia therapy on the expressions of Bcl-2 and Bax. METHODS: Fifty rats were randomly divided into 5 groups, i.e., the control group, the model group, the acupuncture group, the mild hypothermia group, and the combination group (acupuncture in combination of mild hypothermia therapy), 10 in each group. Focal cerebral ischemia model was prepared with modified Longa's suture method. The effects of acupuncture, the mild hypothermia, and the acupuncture in combination of mild hypothermia therapy on the expressions of Bcl-2 and Bax were observed. The indices were detected using immunohistochemical assay. RESULTS: Compared with the control group, the expression of Bcl-2 in the model groups significantly decreased (P < 0.01), and the expression of Bax significantly increased (P < 0.01). Compared with the model group, the expression of Bcl-2 in the three treatment groups significantly increased (P < 0.01) and the expression of Bax significantly decreased (P < 0.01). Compared with the acupuncture group and the mild hypothermia group, the expression of Bcl-2 significantly increased and the expression of Bax significantly decreased in the combination group (both P < 0.01). Compared with the mild hypothermia group, increased expression of Bcl-2 and decreased expression of Bax in the acupuncture group were not obvious (P > 0.05). There was insignificant difference in the therapeutic efficacy between the acupuncture group and the mild hypothermia group. CONCLUSIONS: Both acupuncture and the mild hypothermia therapy could increase the expression of Bcl-2 and decrease the expression of Bax, intervene cerebral ischemia, and protect neurons. In the early cerebral ischemia/reperfusion stage, it is necessary to perform acupuncture and mild hypothermia therapy as soon as possible. PMID- 22303715 TI - [Effects of Dureping Injection on the contents of MMP-9 and TIMP-1 in the lung tissue of mice with pneumonia of influenza virus infection]. AB - OBJECTIVE: To observe the effects of Dureping Injection on the contents of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in the lung tissue of mice with pneumonia of influenza virus infection. METHODS: Sixty-six ICR mice were randomly divided into the normal group, the model group, the low, middle, and high dose Dureping Injection groups (0.435, 0.870, and 1.740 mg/d, respectively), and the positive control group (Ribavirin, 2.500 mg/d), 11 in each. The pneumonia of mice with influenza virus infection model was established using influenza virus strain FM1. Mice were intraperitoneally injected with 0. 3 mL FM1 starting from the infection day, once daily. Five days later mice were killed to calculate the lung index. The pathomorphological changes of the lung tissue were observed using routine HE stained sections. The contents of MMP-9 and TIMP-1 in the homogenate of the lung tissue were detected by ELISA double antibody sandwich method. RESULTS: Compared with the normal group, obvious inflammation occurred in the lung tissue of mice in the model group. The lung index, the content of MMP-9, and the value of MMP 9/TIMP-1 increased significantly in the model group (P < 0.01) , while the content of TIMP-1 was not significantly different (P > 0.05). Compared with the model group, the content of MMP-9 in the low and middle dose Dureping Injection groups, and the positive control group was significantly lowered (P < 0.01). The content of TIMP-1 in the low, middle, and high dose Dureping Injection groups, as well as the positive control group significantly increased (P < 0.01) and the value of MMP-9/TIMP-1 decreased (P < 0.01). CONCLUSION: Dureping Injection could alleviate the inflammatory injury of the lung tissue through decreasing the content of MMP-9, elevating the content of TIMP-1 in the lung tissue, and regulating the value of MMP-9/TIMP-1 of mice with pneumonia of influenza virus infection, thus alleviating the inflammatory injury of the lung tissue. PMID- 22303716 TI - [Effect of salvianolic acid B and tetrahydropalmatine on the L-type calcium channel of rat ventricular myocytes]. AB - OBJECTIVE: To observe the effects of the separate and joint use of salvianolic acid B (SalB) and tetrahydropalmatine (THP) on the L-type calcium channel of rat ventricular myocytes. METHODS: Single isolated ventricular myocytes of rats were obtained using acute enzymolysis separation. The current of the L-type calcium channel was recorded using whole-cell patch clamp technique. Changes of the current peak value of the calcium channel (the vertical distance between the peak value point after activation of the calcium electric current and the electric current track after complete inactivation) were observed before and after medication. RESULTS: The inhibition rate of using SalB (at the dose of 1, 10, and 100 micromol/L) alone on the current peak value of the calcium channel was respectively (25.3 +/- 16.4)% (n=4), (44.6 +/- 24.0)% (n=6), and (86.0 +/- 20.4)% (n =4). That of using THP (at the dose of 10, 30, and 100 micromol/L) alone on the current peak value of the calcium channel was respectively (22.2 +/- 6.4)% (n=5), (27.4 +/- 1.6)% (n= 3), and (51.0 +/- 23.0)% (n=9). The inhibition potency of joint use of SalB (1 micromol/L) and THP (10 micromol/L) on the current peak value of the calcium channel was stronger than using SalB (1 micromol/L) alone or THP (10 micromol/L) alone, showing statistical difference ( P< 0.05). Atropine hydrochloric acid (14 mmol/L) could reverse the inhibition of THP on the L-type calcium channel, while strengthening the inhibition of SalB. CONCLUSIONS: Both SalB and THP showed inhibition on the L-type calcium channel of rat ventricular myocytes. They could generate synergistic effects. Besides, their action mechanisms for regulating the L-type calcium channel were different. PMID- 22303717 TI - [Establishment of gynecological asthenia cold syndrome model]. AB - OBJECTIVE: To establish the model of gynecological asthenia cold syndrome by simulating the etiology of gynecological asthenia cold syndrome depending on 'pathogenic cold impairing yang" in Chinese medicine theory. METHODS: The female SD rats were randomly divided into the model group and the normal group by randomized digital table, 20 in each group. Rats in the model group were placed in 0 degrees C - 1 degree C ice water, and the ice water was placed in 4 degrees C refrigerator, twice daily, 20 min each time, for a total of 30 days. The body temperature was determined and the changes of the estrous cycle were observed every day. When the body temperature decreased (with statistical difference from those of the normal group), and vaginal smears showed disordered estrous cycle, the model was successfully established. Rats were sacrificed during the diestrus period, the correlative indices including reproductive endocrine hormones in blood [follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol ( E2 ), testosterone (T), and progestone (P)], the thyroid function [triiodothyronine (T3), tetraiodothyronine (T4), thyrotropic-stimulating hormone (TSH)], the adrenal function [plasma adrenocorticotropic hormone (ACTH) and cortisol (Cor)], the cellular immune function [serum interleukin-2 (IL-2)], and energy tests [including plasma cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), the ratio of cAMP/cGMP, lactate dehydrogenase(LDH)], an the index of thymus, spleen, uterus, and ovary were detected. RESULTS: Compared with the normal group, rats in the model group appeared chill, dim-color hair, purple and dark ears and claw. They were depressed, scrunched, quiet, and clumsy. They liked to stay together. Their water intake and appetite were reduced, body weight lost, body temperature significantly lowered. They passed loose stool. Their estrous cycle and diestrus were prolonged. Their plasma cGMP content, cAMP/cGMP ratio, LDH, serum IL-2 content, E2, P, T, T3, LH, TSH were significantly lowered to some extent. Their thymus index and the ovary index significantly decreased, showing significant difference (P < 0.05). CONCLUSION: The rat model of gynecological asthenia cold syndrome prepared by extending the frozen time at refrigerator and ice water immersion was in line with clinical features of gynecological asthenia cold syndrome. PMID- 22303718 TI - [Effects of acetoacetate extract of Radix Aconite on hepatic contents of LA, LDH, PA, Gn and ATPase activities in deficient cold model rats]. AB - OBJECTIVE: To observe different effects of acetoacetate extract of Radix Aconite and Radix Aconite Decoction on the energy metabolism in deficient cold model rats. METHODS: Wistar rats were randomly divided into the blank control group (n=10) and the deficient cold model group (n=30). The deficient cold rat model was established using decoction consisting of gypsum, Radix Gentianae, Cortex Phellodendri, and Rhizoma Anemarrhenae. The decoction was given to rats of the deficient cold model group by gastrogavage for 5 days. Then these rats were randomly divided into the acetoacetate extract of Radix Aconite group (n=10), the Radix Aconite Decoction group (n=10), and the model group (n=10). Rats in the model model group were administered with the decoction by gastrogavage. Rats in the other two groups were administered with the acetoacetate extract of Radix Aconite or Radix Aconite Decoction by gastrogavage for 5 days. The contents of lactic acid (LA), lactate dehydrogenase (LDH), pyruvate (PA), glycogen (Gn) and activities of Na(+) -K(+) -ATPase and Ca(2+) -Mg(2+) -ATPase in the hepatic tissue were detected. RESULTS: Compared with the blank control group, the PA content, activities of Na(+)-K(+) -ATPase and Ca(2+) -Mg(2+) -ATPase decreased in the model group. Compared with the model group, the PA content increased in the other two groups. Compared with the control group, the contents of LDH and PA, and activities of Na(+) -K(+) -ATPase increased in the the acetoacetate extract of Radix Aconite group with statistical difference (P < 0.05). CONCLUSIONS: The febricity of acetoacetate extract of Radix Aconite was slightly higher than that of Radix Aconite Decoction, seemingly generating more energy. But the final conclusions and concrete mechanisms of action need further studies. PMID- 22303719 TI - [Study on the regulation of Jiedu Quyu Zishen Recipe on glucocorticoid receptor alpha in the renal tissue of MRL/lpr mice]. AB - OBJECTIVE: To explore the action mechanism of Jiedu Quyu Zishen Recipe (JQZR) on the signal transduction of glucocorticoid receptor alpha (GRalpha) in the renal tissue of MRL/lpr mice. METHODS: Thirty MRL/lpr mice were randomly divided into three groups, i.e., the model group, the Western medicine group, and the Chinese medicine group, 10 in each. Besides, another 10 Kunming mice was taken as the normal control group. The pathological changes of the renal tissue were observed using HE staining. The expression of GRalpha was analyzed using Real-time PCR and Western blot. The effects of JQZR on the binding power of GRalpha to cyclophilin A were detected using co-immunoprecipitation. RESULTS: The renal injury degree of MRL/lpr mice in the Western medicine group and the Chinese medicine group was alleviated. Compared with the model group, the relative quantitation of GRalpha mRNA and protein expressions in the renal tissue of mice in the Western medicine group decreased, while they increased in the Chinese medicine group, showing statistical difference (P < 0.01). JQZR could significantly elevate the binding potency of GRalpha to cyclophilin A. CONCLUSION: Up-regulating the expression of GRalpha and enhancing mutual actions of GRalpha and cyclophilin A was one of JQZR's effects on improving the lesion of the renal tissue. PMID- 22303720 TI - [Effects of Shensu II Recipe on the expressions of transforming growth factor beta1, and plasminogen activator inhibitor-1 in the focal segmental glomerulosclerosis rats]. AB - OBJECTIVE: To observe the effects of Shensu II Recipe on the renal function, mesangial extracellular matrix (ECM) accumulation, the expressions of transforming growth factor-beta1, (TGF-beta1), and plasminogen activator inhibitor-1 (PAI-1) in the focal segmental glomerulosclerosis (FSGS) rats. METHODS: FSGS SD rat model was induced by injecting adriamycin. They were randomly divided into the model group, the Western medicine group, and the Chinese medicine group according to body weight. Besides, another 12 rats was taken as the blank control group. Of them, benazepril (0.33 mg/100 g) was given to rats in the Western medicine group by gastrogavage, while Shensu II Recipe (3.5 g/100 g) was given to rats in the Chinese medicine group by gastrogavage. Normal saline was given to rats in the control group and the model group by gastrogavage. Six rats died during the experiment process, among which, one in the control group, two in the model group, one in the Western medicine group, and two in the Chinese medicine group. The changes of 24 h urinary protein (24 hU, pyrogallol red method), blood urea nitrogen (BUN, urease method), serum creatinine (SCr, enzymatic assay of creatinine), serum total protein (TP, biuret colorimetry), serum albumin (ALB, bromocresol green colormetry) were detected. The pathomorphological changes of the glomerulus were observed. Fibronection (FN), collagen IV (Col IV), glomerulus sclerosis index (GSI), ECM/glomerulus area (GA), expressions of TGF-beta1, and PAI-1 were determined by semi-quantitative analysis. RESULTS: At the end of the 12th week, improvement was shown in the Chinese medicine group (24 hU: 38.55 +/- 2.49 mg; BUN:10.87 +/- 1.78 mmol/L; SCr: 51.70 +/- 1.50 micromol/L; TP: 68.28 +/- 2.31 g/L; and ALB: 42.43 +/- 1.95 g/L). The pathomorphological observation showed that the development of glomerulosclerosis (GS) was significantly slowed down. Semi-quantitative analysis showed significant difference when compared with the model group (GSI: 1.68 +/- 0.33 grade; ECM/GA: 7.11% +/- 2.46%; FN: 4.15% +/- 1.55%; Col IV:1.47% +/- 0.48%; TGF-beta1:19.70% +/- 5.05%; PAI-1: 22.57% +/- 10.65%) ( P < 0.05, P < 0.01). CONCLUSION: Shensu II Recipe could postpone the development of GS in FSGS rats possibly through inhibiting the expressions of TGF-beta1 and PAI-1, hindering the over-accumulation of mesangial matrix. PMID- 22303721 TI - [Regulatory effects of Qinggan Huoxue Recipe on matrix metalloproteinases of alcoholic liver fibrosis rats]. AB - OBJECTIVE: To study the action mechanism of Qinggan Huoxue Recipe (QGHXR) and its disassembled recipes for treatment of alcoholic liver fibrosis (ALF) by observing their regulation on the expressions of matrix metalloproteinases (MMPs) and type 1 tissue inhibitor of metalloproteinase (TIMP-1). METHODS: 130 male SD rats were randomly divided into the blank control group (n=10), the CCI4 group (n=10), and the modeling group (n=110). Rats in the modeling group were intervened by complex factors dominated as alcohol. Eight weeks later they were randomly divided into 4 subgroups, i.e., the model group (n=25), the QGHXR group (n= 15), the Qinggan Recipe (QGR) group (n=15), and the Huoxue Recipe (HXR) group (n=15). Eight model rats were selected for pathological analysis to monitor the development of the modeling at the 4th, 8th, and 10th week of the experiment. The rest rats died during the modeling. Corresponding medicines were given to these treatment groups (at the dose of 4.75 g/kg, 1.50 g/kg, and 3.25 g/kg). All rats were killed at the end of the 12th week. The protein and mRNA expressions of MMP-2, MMP-9, and TIMP 1 were detected using Western blotting, fluorescent quantitative polymerase chain reaction, and immunofluorescence method. RESULTS: Compared with the blank control group, the expressions of MMP-2, MMP-9, and TIMP-1 significantly increased in the model group (1.81 +/- 0.28 versus 0.53 +/- 0.04, 1.60 +/- 0.16 versus 0.45 +/- 0.05, 1.20 +/- 0.02 versus 0.35 +/- 0.07, P < 0.01). Compared with the model group, QGHXR and its disassembled recipes all could decrease the protein and mRNA expressions of TIMP-1 (0. 56 +/- 0.05, 0.67 +/- 0.02, 0.70 +/- 0.02 versus 1.20 +/- 0.02, P < 0.05), increase the expressions of MMP-2 and MMP-9 (4.18 +/- 0.53, 2.70 +/- 0.40, 2.38 +/- 0.22 versus 1.81 +/- 0.28, 3.31 +/- 0.06, 2.56 +/- 0.20, 1.87 +/- 0.05 versus 1.60 +/- 0.16, P < 0.05, P < 0.01). QGHXR was superior to its disassembled recipes (P < 0.05, P < 0.01). CONCLUSION: The action mechanisms of QGHXR and its disassembled recipes might possibly be correlated with regulating MMPs. PMID- 22303722 TI - [Consensus on functional dyspepsia by Integrative Medicine (2010)]. PMID- 22303723 TI - [Consensus on gastroesophageal reflux disease by Integrative Medicine (2010)]. PMID- 22303724 TI - [Development of the theoretical framework and the item pool of the peri-operative recovery scale for integrative medicine]. AB - OBJECTIVE: To study the train of thoughts and procedures for developing the theoretical framework and the item pool of the peri-operative recovery scale for integrative medicine, thus making preparation for the development of this scale and psychometric testing. METHODS: Under the guidance for Chinese medicine theories and the guidance for developing psychometric scale, the theoretical framework and the item pool of the scale were initially laid out by literature retrieval, and expert consultation, etc. RESULTS: The scale covered the domains of physical function, mental function, activity function, pain, and general assessment. Besides, social function is involved, which is suitable for pre operative testing and long-term therapeutic efficacy testing after discharge from hospital. Each domain should cover correlated Zang-Fu organs, qi, blood, and the patient-reported outcomes. Totally 122 items were initially covered in the item pool according to theoretical framework of the scale. CONCLUSIONS: The peri operative recovery scale of integrative medicine was the embodiment of the combination of Chinese medicine theories and patient-reported outcome concepts. The scale could reasonably assess the peri-operative recovery outcomes of patients treated by integrative medicine. PMID- 22303725 TI - [Key points in treating hypertension by integrative medicine]. AB - In China there exist "three high", "three low" and "three no" phenomena in hypertension, so the task of prevention and treatment of hypertension is urgent and difficult. Practices show that treatment by integrative medicine is the best way to prevent and treat hypertension. In clinics several key points should be noticed: holding the difference of therapy philosophy between Chinese medicine and Western medicine, objectively evaluating the curative efficacy of Chinese medicine and Western medicine, insisting on compatible application of Chinese herbs and Western drugs, stressing the combination of disease identification and syndrome typing, preventing and treating target organs' damage in a scientific way, and paying attention to non-drug treatment of hypertension. PMID- 22303726 TI - [Problems and strategies in developing Chinese medicine evidence-based clinical practice guidelines]. AB - Some problems are confronted in the development of Chinese medicine (CM) evidence based clinical practice guidelines in the aspects of individualized treatment, quality of research, reporting bias, safety assessment, and so on. After comprehensive retrieving of current methods for developing evidence-based clinical practice guidelines in the field of complementary and alternative medicine, and an optimal combining with widely accepted standardized methods in evidence-based clinical practice guidelines for allopathic medicine, we put forward strategies for these aforesaid problems. In terms of individualized treatment, practical randomized control trials could be considered for inclusion. In terms of quality of research, the method to formulate guideline recommendations was proposed in case of insufficient evidence. In terms of reporting bias, commonly used databases in complementary and alternative medicine were listed. In terms of safety evaluation, GRADE system was suggested to adopt. PMID- 22303727 TI - [Embodiment of "East Romantic Translation" in the two sets of standard program for English translation of Chinese Medicine terminology]. PMID- 22303728 TI - [The progress of PC12 cells as the oxidative stress cell model]. PMID- 22303729 TI - [The progress of integrative medicine in improving the endometrial acceptability in IVF]. PMID- 22303730 TI - [Stem cells: new concepts in clinic. Interview by Marina Casselyn and Bertrand Kiefer]. PMID- 22303731 TI - [Allergen specific immunotherapy celebrated 100 years in 2011!]. AB - Allergen specific immunotherapy begun 100 years ago, when Leonard Noon published his works. Important progress have been made ever since and numerous studies published. The indications enlarged with the time and thus, more allergen based treatments became available. The purpose of this article is to give a quick review of specific immunotherapy history on occasion of its centenary, and summarize the most important clinical developments reached in 2011 in this field. PMID- 22303732 TI - [Allergo-immunology. Clinical immunology]. AB - The past year has been characterized by significant novelties from the point of view of the clinical immunologist. With the BLISS 52 study showing that belimumab has the ability to decrease the activity of systemic lupus erythematosus (SLE) resistant to conventional therapy an important step towards the control of this difficult disease has been carried forward. In addition, the long-term results of the ALMS study have demonstrated that mycophenolate mofetil is superior to azathioprine in maintaining the remission in patients with severe lupus nephritis. Furthermore, the results of the RAVE and RITUXVASC studies have documented that rituximab is a valid alternative to cyclophosphamide in the control of ANCA associated vasculitis. PMID- 22303733 TI - [Addiction]. AB - The news in addiction medicine for 2011 include new knowledges coming from the neurosciences, but also new clinical concepts, as the role of hospital addiction units in an integrated network of care. The issue of cocaine vaccination is discussed from an ethical point of view. Finally, the integration of mindfulness techniques is introduced as a useful approach in the treatment of the addictions. PMID- 22303734 TI - [Endocrinology]. AB - Recent discoveries in molecular biology offer new perspectives in the treatment of endocrine tumors. There is currently no medical therapy for Cushing's disease that targets the pituitary adenoma. Pasireotide, a new somatostatin analog, demonstrates a strong affinity for somatostatin receptors expressed by corticotroph adenomas. Some recent clinical trials showed a decrease of urinary free cortisol with pasireotide. This new treatment could be useful in case of pituitary surgery failure. Thyroid tumorigenesis involves kinase signaling cascade. Tyrosine-kinase inhibitors have now been tested in the treatment of progressive differentiated iodine refractory thyroid carcinomas or medullary carcinomas and showed modestly encouraging results. PMID- 22303735 TI - [Review in geriatric medicine 2011]. AB - In 2011, new tools to evaluate life expectancy are available. Controversy about PSA-based screening for prostate cancer is still going on, with new data from the US Preventive services task force. A brief behavioral treatment for insomnia can be efficient and durable. Gliptines are be useful to avoid treatment-induced hypoglycemia in diabetic patients. New Alzheimer diagnostic criteria, including biomarkers, have been published. PMID- 22303736 TI - [Obstructive sleep apnea and drugs as causes of treatment-resistant hypertension]. AB - Treatment-resistant hypertension is still common despite the availability of several types of antihypertensive agents acting by different mechanisms. The existence of refractory hypertension should lead to rule out "white-coat hypertension", poor adherence to prescribed drugs as well as classical causes of secondary hypertension such as renal artery stenosis, primary aldosteronism, pheochromocytoma and renal disease. It is also important to consider the possible existence of obstructive sleep apnea or the regular intake of vasopressive drugs or substances. PMID- 22303737 TI - [2011 news in infections diseases: selected readings]. AB - A study published in 1998 linking MMR vaccine and autism was recently retracted by the Lancet because the data were falsified. The impressive reduction of invasive pneumococcal diseases with the 7-valent pneumococcal conjugate vaccine is due to a more than 90% reduction in rates of infections due to vaccinal serotypes at the expense of a slight increase in non-vaccinal serotypes. Genes encoding resistance factors to several antibiotic classes were detected in 30000 year-old samples. New Delhi metallo-beta-lactamase 1 was frequently detected in street water in New Dehli. Azithromycin decreased COPD exacerbations in a select group of patients with COPD at the cost of more frequent small decrements in hearing. Cranberry juice did not prevent recurrent urinary tract infections. Some patients with persistent symptoms after Lyme disease had higher levels of anti Borrelia antibodies than cured patients. PMID- 22303738 TI - [Emergency medicine: updates 2011]. AB - Emergency medicine physicians aim to stabilize or restore vital functions, establish diagnosis, initiate specific treatments and adequately orientate patients. This year, new evidences have improved our knowledge about diagnostic strategy for patients with acute non traumatic headache, treatment of acute atrial fibrillation and outpatient management of acute pulmonary embolism. Reducing injection pain of local anesthetics, reducing irradiation by using alternative diagnostic tools in appendicitis suspicion, and identification of trauma patients who benefit from tranexamic acid administration are other illustrations of the efforts to improve efficacy, safety and comfort in the management of emergency patients. PMID- 22303739 TI - [Nephrology]. AB - Several landmark studies have recently been published in nephrology. In summary, mycophenolate mofetil is superior to azathioprine in maintaining remission and preventing relapse in lupus nephritis. For patients with type I diabetes, long term renal function is better preserved when optimal glycaemic control is obtained with intensive diabetes therapy from the onset of disease, and in patients with type 2 diabetes treatment with bardexolone may increase renal function. With respect to chronic kidney disease, the association of simvastatine and ezetimibe is effective in improving cardiovascular outcomes. There is no need to initiate dialysis in asymptomatic patients, and daily haemodialysis seems better than three times weekly hemodialysis. Finally, N-acetylcysteine does not prevent contrast nephropathy. PMID- 22303740 TI - [Neurology]. AB - In 2011, new oral anticoagulants for atrial fibrillation are available and the ABCD3-I score predicting stroke after TIA updates the ABCD2 score. New McDonald criteria allow faster MS diagnosis and the first oral treatment (fingolimod) for MS can be prescribed. A new anti-antiepileptic drug (retigabine) is available and sodium valproate has long term neurological adverse effects after in utero exposure. Among Parkinson disease treatments, deep brain stimulation is extending applications and dopamine agonists with extended release are as efficient and well tolerated as standard forms at long term scale. Monoclonal antibodies and immunosuppressant agents are proposed as good alternatives in the treatment of chronic dysimmune polyneuropathies. Gene therapy for the treatment of genetic myopathies is progressing. PMID- 22303741 TI - [Pediatrics]. AB - Several preliminary studies suggest that prophylactic administration of probiotics reduces the incidence of necrotizing enterocolitis (NEC) in preterm infants, and several neonatology units have introduced this treatment under strict surveillance. Nonetheless, breast milk feeding remains the mainstay of NEC prevention. The beta-blocker propranolol, known for its effectiveness on cutaneous hemangiomas, is also proving useful for the treatment of subglottic or visceral hemangiomas. Following the decrease in severe bacterial infections thanks to widespread vaccinations, the McCarthy clinical score has regained importance in the prediction of the risk of bacterial infection in febrile infants. It is easy to use, economical, and has a diagnostic value comparable to laboratory tests. The new WHO growth charts have been introduced in Switzerland in 2011 to take into account the increasing regional and ethnic variations in our country. Any significant change in growth velocity should prompt an evaluation of the need of further investigations. PMID- 22303742 TI - [Canakinumab: a promising treatment in rheumatology]. AB - In auto-inflammatory diseases, the role of the inflammasome and the interleukine IL-1beta has recently been shown. Thus, the physiopathology of rare diseases as Cryopyrin-associated periodic syndrome (CAPS) is better understood. In the era of biologics, new treatments targeting IL-1 have been developped. Canakinumab is a fully humanized monoclonal antibody inhibiting specifically IL-1beta Clinical studies have shown its efficacy on clinical symptoms and on inflammatory markers in patients with rare diseases such as CAPS or idiopathic juvenile arthritis, but also in more common rheumatic conditions like gout. Canakinumab has been approved in Switzerland only for the treatment of CAPS. Studies evaluating its effect on cardiovascular diseases are ongoing. PMID- 22303743 TI - [Urology in 2011]. AB - In 2011, therapeutic acquisitions in urology allow optimizing management of acute uncomplicated cystitis and acute pyelonephritis by female patients and in men clinical implications of benign prostatic hyperplasia opposed to prostate cancer detection as well as hormonal treatment of advanced prostate cancer. PMID- 22303744 TI - [The mucisian's cramp. About the illness of Robert Schumann]. AB - The musicians are seen in daily neurological practice facing various problems sometimes simple such as skeletal or tendon pain or even compression of a nerve trunk and sometimes more complicated such as focal dystonia. Dystonia often has a dramatic impact on the career of a musician given the complexity of the clinical and therapeutic approach and the results are often disappointing. The history of the German Romantic composer Robert Schumann illustrates this reality; through his story a discussion of both the different pathophysiological hypotheses responsible for focal dystonia, a disorder of brain plasticity, and of the multimodal therapeutic approaches, revisited in the light of neurophysiological findings will be described. PMID- 22303745 TI - [Management of renal anemia in patients with chronic kidney disease: the role of the general practitioner]. AB - The prevalence of chronic kidney disease (CKD) is high and diabetic nephropathy is a leading cause of CKD. One of the most common complications of CKD is anemia, the frequency and severity of which increase as kidney failure progresses. Renal anemia is primarily caused by reduced renal erythropoietin production. It can also be associated with iron deficiency caused by reduced iron absorption, occult blood loss and impaired iron mobilization. This work provides an overview of the management of renal anemia with focus on intravenous iron therapy, which is more effective than oral iron administration in CKD due to reduced iron absorption. PMID- 22303746 TI - [Dyslexia; Charcot-Marie-Tooth; reductionism]. PMID- 22303747 TI - [Whose need is it?]. PMID- 22303748 TI - [Autism, history of genes and small business]. PMID- 22303749 TI - [Ten thousand euros for not honoring his wife]. PMID- 22303750 TI - [2012, and human evolution]. PMID- 22303751 TI - Staging and comorbidities. AB - Articular cartilage lesions of the distal femur and patella are common. To provide an accurate diagnosis of a clinically symptomatic cartilage lesion and subsequent appropriate planning for potential treatment options, a proper staging is required. This includes clinical exam, radiographic imaging as well as arthroscopy. Once the staging is completed, other comorbidities may need to be addressed that may require additional surgical procedures. These can either be planned as staged procedures or concomitantly with a cartilage repair procedure. This article will discuss this staging and evaluation process in depth to serve as a guideline to the orthopaedic surgeon engaged in the treatment of cartilage defects in patients with early posttraumatic osteoarthritis (OA). PMID- 22303752 TI - Magnetic resonance imaging of cartilage repair techniques. AB - Magnetic resonance (MR) imaging offers a noninvasive method to assess cartilage repair, allowing objective evaluation of the repair tissue and insight into the natural history of cartilage repair procedures. MR imaging allows assessment of the percent fill, signal morphology of the repair tissue, subchondral bone and three-dimensional geometry of the joint. The information gained from MR imaging therefore plays a valuable role in patient follow-up after cartilage repair. This article discusses the MR imaging techniques available for the assessment of articular cartilage, including quantitative imaging techniques that allow assessment of cartilage biochemistry. The MR imaging appearance and assessment of microfracture, autologous chondrocyte implantation, and osteochondral autograft and allograft transplantation is reviewed. PMID- 22303753 TI - Evolving biomarkers in osteoarthritis. AB - Osteoarthritis (OA) is one of the most debilitating diseases affecting mankind with severe financial and emotional consequences. The heterogeneity of the human population, lack of complete understanding of the OA disease process, and the slow progressive nature of the disease characterized by prolonged periods of nonsymptomatic, degenerative changes has hampered development of ideal diagnostic and prognostic portfolios. The difficulties associated with early OA diagnosis by exclusively radiographic techniques has propelled a need to identify specific biomarkers for rapid and effective early OA diagnosis, better patient prognosis, and for monitoring the efficacy of pharmacological interventions to the disease process. This review highlights some of the biochemical biomarkers in current use in OA, their applications and limitations. Investigation of single nucleotide polymorphisms as genetic biomarkers and the application of technologies such as lipidomics and metabolomics to OA are generating potentially additional biomarkers that could be helpful for detecting early OA phenomena in humans. PMID- 22303754 TI - Using animal models in osteoarthritis biomarker research. AB - Osteoarthritis (OA) is a disease that commonly affects human and veterinary patients. Animal models are routinely used for OA research, and the dog is a nearly ideal species for translational investigation of human OA biomarkers. The cytokine, chemokine, and matrix metalloprotease (MMP) profiles of synovial fluid, serum, and urine from dogs with surgically induced and naturally occurring OA were compared with dogs without OA using xMAP technology (Qiagen Inc., Valencia, CA). Markers that exhibited significant differences between groups were identified (monocyte chemoattractant protein 1 [MCP1], interleukin 8 [IL8], keratinocyte-derived chemoattractant [KC], and MMP2 and MMP3), and their sensitivities and specificities were calculated to determine their diagnostic usefulness in a future biomarker panel. Synovial fluid IL8 was the most sensitive, but MCP1 was also highly sensitive and specific. The alterations in KC suggested that it may differentiate between cruciate disease and other types of OA, and the MMPs were most sensitive and specific in the serum. This study provided additional insight to the participation of cytokines, chemokines, and MMPs in OA, and potential diagnostic biomarker candidates were identified. A brief literature review of other biomarker candidates previously examined using animal models is discussed. PMID- 22303755 TI - Total knee arthroplasty in patients with fibromyalgia. AB - Fibromyalgia has recently emerged as a diagnosis of exclusion for patients with chronic, widespread pain. We investigated the influence of this comorbidity on outcomes of total knee arthroplasty (TKA). We matched 59 patients (90 knees) who underwent primary TKA with a diagnosis of fibromyalgia to control patients who underwent the same surgery. Postoperative satisfaction and functional outcomes were assessed using a Likert scale and the SF-36 survey, respectively. At 3.4 years' follow-up, fibromyalgia patients were less satisfied with TKA than control patients, and had lower preoperative and postoperative SF-36 scores. They demonstrated improvement comparable to that of controls following TKA, however. Fibromyalgia patients appear to show improvement comparable to that of controls following surgery. This syndrome should not be considered a contraindication for surgery. PMID- 22303756 TI - Unicompartmental and total knee arthroplasty in the same patient. AB - This prospective randomized study compared the clinical and radiographic outcomes of unicompartmental knee arthroplasty versus total knee arthroplasty. The group consisted of 34 patients (19 males and 15 females), who had a mean age of 73 years (range, 49 to 86 years), and who fit the criteria for bilateral unicompartmental knee arthroplasty. Each patient received a unicompartmental prosthesis in one knee and a total knee arthroplasty in the other during a single anesthetic session. At a mean follow-up of 5 years (range, 24 to 89 months), the Knee Society pain and function scores were similar for both groups. There were no radiographic failures. Survivorship of the unicompartmental group was 85% compared with 100% in the total knee group (p = 0.05). All of the prostheses that failed had an all-polyethylene tibial component. These results suggest that unicompartmental knee arthroplasty may not offer similar survivorship when compared with total knee arthroplasty. PMID- 22303757 TI - Total knee arthroplasty in patients over 80 years of age. AB - We conducted this study to review the clinical and radiographic outcomes of patients 80 years of age or older who underwent total knee arthroplasty (TKA). We identified clinical results in 60 patients (66 knees) who had a mean age of 84 years (range, 80 to 95 years) and who underwent TKA. These were compared with a non-age-matched group of 63 patients (66 knees) who had a mean age of 69 years (range, 60 to 79 years). Four patients were lost to follow-up. After a mean 43 month follow-up (range, 24 to 117 months), Knee Society pain and function scores for the study group improved from 53 points (range, 25 to 70 points) and 53 points (range, 40 to 70 points), respectively, to 94 points (range, 75 to 100 points) and 87 points (range, 45 to 100 points). There were no implant failures, 2 surgical complications, and 13 medical complications. In the matching group, there were four surgical complications (two required revision) and two medical complications. There were no radiographic failures or progressive radiolucencies. Although the incidence of medical complications in the perioperative period may be higher, TKA is a safe and effective treatment for refractory joint pain in patients over 80 years of age. PMID- 22303758 TI - Interference screw fixation using bioabsorbable screw as void filler. AB - We evaluated interference screw fixation in a plug-tunnel construct using bioabsorbable screws as void fillers with different percentages of the screw removed. Nine-millimeter tunnels in a closed-cell foam block were filled with a 10-mm bioabsorbable screw, and 10-mm revision tunnels were placed in parallel with tunnel overlap resulting in removal of 10%, 25%, or 50% of the screw diameter. Synthetic bone plugs were fashioned to fit 10-mm tunnels. In all groups, the plugs were secured in standard interference fixation with a 9-mm metal screw between the void-filling bioabsorbable screw and plug. Failure loads for the control group (no revision tunnel) averaged 926 +/- 44 N, 10% (1024 +/- 129 N) and 25% (932 +/- 129 N) groups were not significantly different; failure load in the 50% diameter group (780 +/- 72 N) was significantly lower than all other groups (p < 0.001). Using a bioabsorbable screw as void filler provided mean load to failure not different from that of standard reconstruction when 10 and 25% of the diameter of the void-filling screw was removed. Load to failure was significantly lower when 50% of the void-filling screw diameter group was removed. This may be applicable in anterior cruciate ligament reconstruction where a previous tunnel void has to be addressed. PMID- 22303759 TI - Revision ACL reconstruction outcomes: MOON cohort. AB - Many clinicians believe that the results of revision anterior cruciate ligament (ACL) reconstruction compare unfavorably with primary ACL reconstruction. However, few prospective studies have evaluated revision ACL reconstruction using validated patient-based metrics. This study was performed to evaluate and compare the results of revision ACL reconstruction and primary ACL reconstruction. The Multicenter Orthopaedic Outcomes Network consortium is an NIH-funded, hypothesis driven, multicenter prospective cohort study of patients undergoing ACL reconstruction. All patients preoperatively complete a series of validated patient-oriented questionnaires. At scheduled 2-year follow-up all patients are given the same series of questionnaires to complete. The study evaluated the results of 2-year follow-up of revision ACL reconstruction performed in 2001. Parameters evaluated included Marx activity level, Knee Injury and Osteoarthritis Outcome Score (KOOS), and International Knee Documentation Committee (IKDC) scores. For this study 446 subjects met inclusion criteria; 2-year follow-up was obtained on 393 (88%). The study group consisted of 55% males with median age of 22 years. There were 33 revision ACL reconstruction cases, for which follow-up was available for 29 (88%). Median baseline Marx (interquartile range) was 12 (8 to 16) and 12 (6 to 16) for the primary ACL reconstruction and revision ACL reconstruction groups, respectively (p= 0.81). At 2 years, median Marx was 9 (4 to 13) and 5 (0 to 10) for the primary ACL reconstruction and revision ACL reconstruction groups, respectively (p= 0.03). Median 2-year IKDC was 75.9 (revision) versus 83.9 (primary) (p=0.003). Median KOOS subscale Knee Related Quality of Life (KRQOL) at 2 years was 62.5 (revision) versus 75 (primary) (p < 0.001), subscale Sports and Recreation was 75 (revision) and 85 (primary) (p = 0.005), subscale Pain was 83.3 (revision) and 91.7 (primary) (p= 0.002). Marx activity score declined at 2-year follow-up in revision ACL reconstruction compared with primary ACL reconstruction. IKDC and KRQOL were significantly decreased in revision ACL reconstruction compared with primary ACL reconstruction at 2-year followup. Revision ACL reconstruction resulted in a significantly worse outcome as measured by these patient-based measures at 2 years. PMID- 22303760 TI - Diagnosis and treatment of postsurgical synovial fistula of the knee. AB - With the exception of post-arthroscopy synovial fistulae formation, which generally heal without additional treatment, postsurgical synovial fistulae are relatively uncommon. We describe the development of synovial fistulae after three different surgical procedures: a biopsy, a high tibial osteotomy, and an anterior cruciate ligament reconstruction. With treatment tailored to the individual patient, the synovial fistulae can be cured by closing the opening between the knee joint and the fistula. PMID- 22303761 TI - Juxta-articular myxoma of the knee. AB - Juxta-articular myxoma is a benign lesion usually presenting as a slow-growing, well-circumscribed mass. Occasionally, however, the lesion grows rapidly and is poorly circumscribed, and it is this clinical presentation that arouses suspicion of malignancy. Furthermore, on histology a myxoma can also be confused with a variety of sarcomas. We present a case of juxta-articular myxoma and discuss the possible diagnostic dilemmas involved. PMID- 22303762 TI - Introduction: in the aftermath of the so-called memory wars. AB - The term "memory wars" has been used by some to characterize the intense debate that emerged in the 1990s regarding the veracity of recovered memories of child sexual abuse. Both sides in this debate have been motivated by scientific and ethical concerns. Recent years have witnessed a burgeoning of relevant behavioral and neuroimaging evidence that when taken together, points the way toward reconciliation. All of the contributors to this volume acknowledge that true recoveries characterize a substantive proportion of recovery experiences and that suggestive therapeutic techniques may promote false memories. Disagreements continue to exist on the cognitive and motivational processes that can lead to true recoveries and the extent to which false recovered memories occur. PMID- 22303763 TI - The cognitive neuroscience of true and false memories. AB - Of central relevance to the recovered/false memory debate is understanding the factors that cause us to believe that a mental experience is a memory of an actual past experience. According to the source monitoring framework (SMF), memories are attributions that we make about our mental experiences based on their subjective qualities, our prior knowledge and beliefs, our motives and goals, and the social context. From this perspective, we discuss cognitive behavioral studies using both objective (e.g., recognition, source memory) and subjective (e.g., ratings of memory characteristics) measures that provide much information about the encoding, revival and monitoring processes that yield both true and false memories. The chapter also considers how neuroimaging findings, especially from functional magnetic resonance imaging studies, are contributing to our understanding of the relation between memory and reality. PMID- 22303764 TI - Towards a cognitive and neurobiological model of motivated forgetting. AB - Historically, research on forgetting has been dominated by the assumption that forgetting is passive, reflecting decay, interference, and changes in context. This emphasis arises from the pervasive assumption that forgetting is a negative outcome. Here, we present a functional view of forgetting in which the fate of experience in memory is determined as much by motivational forces that dictate the focus of attention as it is by passive factors. A central tool of motivated forgetting is retrieval suppression, a process whereby people shut down episodic retrieval to control awareness. We review behavioral, neurobiological, and clinical research and show that retrieval suppression leads us to forget suppressed experiences. We discuss key questions necessary to address to develop this model, relationships to other forgetting phenomena, and the implications of this research for understanding recovered memories. This work provides a foundation for understanding how motivational forces influence what we remember of life experience. PMID- 22303765 TI - Searching for repressed memory. AB - This chapter summarizes the work of my research group on adults who report either repressed, recovered, or continuous memories of childhood sexual abuse (CSA) or who report no history of CSA. Adapting paradigms from cognitive psychology, we tested hypotheses inspired by both the "repressed memory" and "false memory" perspectives on recovered memories of CSA. We found some evidence for the false memory perspective, but no evidence for the repressed memory perspective. However, our work also suggests a third perspective on recovered memories that does not require the concept of repression. Some children do not understand their CSA when it occurs, and do not experience terror. Years later, they recall the experience, and understanding it as abuse, suffer intense distress. The memory failed to come to mind for years, partly because the child did not encode it as terrifying (i.e., traumatic), not because the person was unable to recall it. PMID- 22303766 TI - A theoretical framework for understanding recovered memory experiences. AB - If recovered memory experiences appear counter-intuitive, this is in part due to misconceptions about trauma and memory, and to a failure to adopt a comprehensive model of memory that distinguishes personal semantic memory, autobiographical event memory, and memory appraisal. Memory performance is generally superior when events, including traumas, are central to identity. Prolonged trauma in childhood, however, can produce severe identity disturbances that may interfere with the encoding and later retrieval of personal semantic and autobiographical event information. High levels of emotion either at encoding or recall can also interfere with the creation of coherent narrative memories. For example, high levels of shock and fear when memories are recovered unexpectedly may lead to the experience of vivid flashbacks. Memory appraisals may also influence the sense that an event has been forgotten for a long time. Recovered memories, although unusual, do not contradict what we know about how memory works. PMID- 22303767 TI - Cognitive underpinnings of recovered memories of childhood abuse. AB - Recent research on recovered memories of childhood sexual abuse has shown that there are at least two types of recovered memory experiences: those that are gradually recovered within the context of suggestive therapy and those that are spontaneously recovered, without extensive prompting or explicit attempts to reconstruct the past. These recovered memory experiences have different origins, with people who recover memories through suggestive therapy being more prone to forming false memories, and with people who report spontaneously recovered memories being more prone to forgetting prior instances of remembering. Additionally, the two types of recovered memory experiences are linked to differences in corroborative evidence, implying that memories recovered spontaneously, outside of suggestive therapy, are more likely to correspond to genuine abuse events. This chapter highlights the background of the recovered memory debate, summarizes recent studies with individuals reporting recovered memory experiences and points towards applications in the justice system and in clinical practice. PMID- 22303768 TI - Motivated forgetting and misremembering: perspectives from betrayal trauma theory. AB - Individuals are sometimes exposed to information that may endanger their well being. In such cases, forgetting or misremembering may be adaptive. Childhood abuse perpetrated by a caregiver is an example. Betrayal trauma theory (BTT) proposes that the way in which events are processed and remembered will be related to the degree to which a negative event represents a betrayal by a trusted, needed other. Full awareness of such abuse may only increase the victim's risk by motivating withdrawal or confrontation with the perpetrator, thus risking a relationship vital to the victim's survival. In such situations, minimizing awareness of the betrayal trauma may be adaptive. BTT has implications for the larger memory and trauma field, particularly with regard to forgetting and misremembering events. This chapter reviews conceptual and empirical issues central to the literature on memory for trauma and BTT as well as identifies future research directions derived from BTT. PMID- 22303769 TI - Epilogue: continuing points of contention in the recovered memory debate. AB - Four contentious issues in the recovered memory debate are explored. Volume contributors offer differing perspectives on the generalizability of laboratory research, on the role of emotion in memory, on the prevalence of false recoveries, and on the motivations that underlie differences in opinion, especially with regard to whether the debate ought to be framed within a larger sociopolitical context. The recovered memory debate is argued to center on two ethical concerns that happen to be in conflict, equality among groups on one hand and due process protections on the other. Additional movement toward reconciliation is possible with a fair assessment of all available evidence, with a mutual understanding of differing perspectives, and with civil discourse. PMID- 22303770 TI - [The discovery of blood circulation: revolution or revision?]. AB - The discovery of the principle of blood circulation by William Harvey is generally considered as one of the major events of the "scientific revolution" of the 17th century. This paper reconsiders the question by taking in account the way Harvey's discovery was discussed by some contemporary philosophers and physicians, in particular Fontenelle, who insisted on the necessity of redefining methods and principles of medical knowledge, basing themselves on the revival of anatomy and physiology, and of its consequences on the way it permits to think about the human nature. This return allows us to consider the opportunity of substituting the kuhnian scheme of "structure of scientific revolutions" for the bachelardian concept of "refonte". PMID- 22303771 TI - The piano plague: the nineteenth-century medical critique of female musical education. AB - The role of music in nineteenth-century female education has been seen primarily in the context of the middle class cult of domesticity, and the relationship of music to medicine in the period has generally been viewed in terms of music therapy. Nevertheless, for much of the century there was serious medical discussion about the dangers of excessive music in girls' education. Many of the leading psychiatrists and gynaecologists of the nineteenth century argued that music could over-stimulate the nervous system, playing havoc with vulnerable female nerves and reproductive organs, and warned of the consequences of music lessons on the developing bodies of teenage girls. Two rival models of music's effects competed and were combined. One suggested that music led to illness by provoking sensuality, imagination and sexuality; the other argued that it was a source of neurasthenic fatigue because of intellectual strain. PMID- 22303772 TI - [Interpretation of writings in the psychopathologic approach to spiritualism (1850 - 1950)]. AB - We propose a chronological review of the psychopathological interpretations of writings produced by spiritualists during their practices of trance or by spiritualists turned delirious. The interest is to highlight the exemplary role that psychiatrists or psychopathologists made attributed to mediumnism in the elaboration of psychiatric knowledge. PMID- 22303773 TI - Doctors in court, honour, and professional ethics: two scandals in Imperial Germany. AB - Comparing two public medical affairs which involved disciplinary proceedings and libel actions, one from Bavaria and one from Prussia, this article analyzes the dynamics behind legal conflicts over doctors' professional ethics in Imperial Germany. In both the case of Dr Maurice Hutzler, who committed suicide after conflicts with senior colleagues at the Gisela Children's Hospital and a sentence of the court of honour of the Munich Medical District Society, and the Berlin "patient trade" affair, in which the medical professors Ernst von Leyden, Hermann Senator, Karl Anton Ewald and Carl Posner were accused of having made payments to middlemen for bringing them lucrative private patients, notions of personal and professional honour played a central role. The Munich case highlighted shortcomings of the Bavarian medical court of honour system, which was less developed than its Prussian counterpart. The analysis of the two cases suggests that the ethics of medical practice in early twentieth-century Germany should be viewed as part of a culture of honour. PMID- 22303774 TI - Am I my brain or my genitals? A nature-culture controversy in the hermaphrodite debate from the mid-1960s to the late 1990s. AB - The groundbreaking and prophetic rhetoric of neuroscience has recently highlighted the fetal brain as the most promising organ for understanding why transsexuals feel "trapped in the wrong body", and for predicting whether children born with "ambiguous" genitalia will grow up to feel like a man or a woman.This article proposes a recent history of the cerebralization of intersexuality and of transsexuality as atypical neurodevelopmental conditions. It examines the ways in which the organizational theory of brain sex differentiation developed in the late 1950s in behavioral neuroendocrinology has gained increased prominence in and through controversies over best practice issues in the case management of intersex newborns, and the etiology of transsexuality.It focuses on the American context and on the leading warrior in this battle: Milton Diamond, now a most prominent figure in professional debates about the clinical management of intersexuality, and the intersex person's best friend. Persons with an intersexed or transsexual condition consider, not their gonads, but their brains, their core sense of self, as the primary determinant of sex. (Diamond and Beh 2005, 6-7, note 1) PMID- 22303775 TI - Kathleen Mears Memorial Lecture: Are we ready for 2014? An overview of healthcare reform for the neurodiagnostic practitioner. AB - U.S. Healthcare is not a system but a fragmentation of care delivery mechanisms. Healthcare Reform drives at reducing costs through access, quality, and efficiency. The U.S. economy contracted in 2007 and healthcare spending increased consuming an even greater and potentially unsustainable share of the economic wealth. Affordable care means "shared risk." The Patient Protection and Accountable Care Act (PPACA) was signed into law on March 23, 2010. The bill outlines the next ten years for new policies and pilot programs. More profound for us are the many provisions that promote fundamental delivery system reform. At this time, the burden of leadership is immense. Our profession needs a large cadre of qualified leaders to shape the future. PMID- 22303776 TI - Intraoperative neurophysiological monitoring (IONM): lessons learned from 32 case events in 2069 spine cases. AB - Intraoperative neurophysiological monitoring (IONM) is becoming the standard of care for many spinal surgeries, especially those with deformity correction and instrumentation. We reviewed 2069 spine cases with multimodality IONM including somatosensory evoked potentials (SSEP), transcranial electrical motor evoked potentials (TCeMEP), and spontaneous and triggered electromyography (s-EMG and t EMG) in a University setting over a period of four years to examine perioperative clinical findings when an IONM event was noted and to ascertain how IONM has affected our ability to avoid potential neurological injury during spine surgery. We performed a retrospective analysis of cases from 2006 to 2010 to study the frequency and cause of intraoperative events detected via IONM and the clinical outcome of the patient. There were 32 cases (1.5%) with possible intraoperative events. There were 17 (53%) cases where IONM changes affected the course of the surgery and prevented possible postoperative neurological deficits. Seven cases (41%) were due to deformity correction, five (29%) due to hypotension, four (24%) due to patient positioning, and one (6%) due to a screw requiring repositioning. None of the 17 patients had postoperative motor or sensory deficits. There were four cases with false-positive IONM findings due to correctible technical issues. Three cases required surgical revision due to pedicle screw malposition. In each case, s-EMGs failed to exhibit intraoperative changes but the patient presented with postoperative radiculopathy. We believe that the use of t-EMGs may have prevented these complications. This review reinforces the importance of multimodality IONM for spinal surgery. The incidence of possible events in our series was 1.5%, and several likely postoperative neurologic deficits were avoided by intraoperative intervention. PMID- 22303777 TI - Transcranial motor evoked potential changes induced by provocative testing during embolization of cerebral arteriovenous malformations in patients under total intravenous anesthesia. AB - Cerebral motor evoked potential (MEP) monitoring during arteriovenous malformation (AVM) embolization is not well studied (Soderman et al. 2003). Alterations of cerebral blood flow (CBF) during cerebral embolization could cause ischemia/infarction to the cerebral cortex. Permanent loss of MEPs is correlated with a permanent motor deficit. We report a case of a patient undergoing AVM embolization during which transcranial electrical motor evoked potentials (TCeMEP) reliably predicted changes to CBF induced by selective methohexital testing. Our finding demonstrated that MEPs are a useful means of intraoperative monitoring of motor pathway integrity and predicting changes. The loss of MEP predicted and prevented severe postoperative motor deficits. Intraoperative neuromonitoring with SSEP, TCeMEP and continuous EEG revealed no changes until the posterior cerebral artery (PCA), but not the anterior cerebral artery (ACA), was injected. TCeMEP may be superior to somatosensory evoked potential (SSEP) and EEG monitoring in predicting motor impairment during AVM surgery. PMID- 22303778 TI - Detection and prevention of impending brachial plexus injury secondary to arm positioning using ulnar nerve somatosensory evoked potentials during transaxillary approach for thyroid lobectomy. AB - Robotic assisted surgery is becoming widely used for procedures such as radical prostatectomy. The use of robotic assisted surgery to perform partial and complete thyroidectomies using a transaxillary approach is being investigated in patient populations who wish to avoid a conspicuous cervical scar. Patient positioning for this approach as well as retraction during exposure has the potential to result in postoperative brachial plexopathy similar to what is seen in other types of surgery. We report the use of ulnar nerve somatosensory evoked potentials (SSEPs) to detect and prevent positional related neuropathy in the first pediatric patient in the world to undergo this procedure. We conclude that upper extremity SSEPs should be routinely performed during robotic assisted thyroidectomy. PMID- 22303779 TI - Waveform window #21. Anomaly during pedicle screw stimulation. PMID- 22303780 TI - The effect of pitch type on ground reaction forces in the baseball swing. AB - Coaches have identified the batter's weight shift as a critical component for promoting proper timing and balance in a baseball swing. Analysing the weight shift through maximum horizontal (Fx) and vertical (Fz) ground reaction forces (GRFs) of professional batters (N = 29; height = 185 +/- 6 cm; mass = 92 +/- 9 kg), the purpose of this study was to compare GRFs among swings against fastballs and changeups. General linear models were used to compare three conditions of interest: successful results against fastballs, successful results against changeups, and unsuccessful results against changeups. Batters had a similar loading mechanism and initial weight transfer from back foot to front foot regardless of pitch type, but peak front foot GRFx and GRFz occurred with significantly different magnitudes and at significantly different times, depending on the pitch type and hit result. Peak front foot GRFs were greater for successful swings against fastballs compared to both successful and unsuccessful swings against changeups. Peak front foot GRFs of unsuccessful swings against changeups occurred, on average, 15-20 ms earlier than successful swings against changeups and 30-35 ms earlier than successful swings against fastballs, quantifying how a changeup can disrupt the coordination of a hitter's weight shift. PMID- 22303781 TI - Whole-body vibration effects on the muscle activity of upper and lower body muscles during the baseball swing in recreational baseball hitters. AB - The purpose of this study was to evaluate the effects of whole-body vibration (WBV) on the muscle recruitment of selected upper and lower body muscles during the baseball swing. Participants were recreationally trained males (n = 16, 22 +/ 2 years, 181.4 +/- 7.4 cm, 84.7 +/- 9.0 kg), with previous baseball experience. Subjects participated in three randomized sessions on separate days, consisting of three sets of five swings offa hitting tee. Exercises (upper and lower body dynamic and static movements) with or without WBVexposure were performed between swing sets. During each swing, the gastrocnemius, biceps femoris, gluteus maximus, pectoralis major, latissimus dorsi, and triceps brachii were evaluated for electromyographic (EMG) activity. EMG values were normalized to EMG measured during maximal voluntary isometric contraction. Statistical analysis revealed no significant differences in EMG activity across the three treatments. In addition, the results displayed a specific muscle recruitment order during the swing, starting with the lower body followed by the upper body muscles. This study was the first to report the recruitment order during the baseball swing. Although acute exposure to WBV did not significantly alter the muscle recruitment, these results may prove useful for practitioners looking to enhance baseball swing performance. PMID- 22303782 TI - Enhancing cricket batting skill: implications for biomechanics and skill acquisition research and practice. AB - This review synthesises the biomechanical and skill acquisition/sport expertise literature focused on the skill of cricket batting. The literature is briefly reviewed and the major limitations, challenges, and suggested future research directions are outlined. This is designed to stimulate researchers to enhance the understanding of cricket batting biomechanics and skill acquisition and in turn assist cricket coaches develop efficacious batting skill development programmes. An interdisciplinary approach between biomechanists and skill acquisition specialists is advocated to further knowledge of the underlying processes and mechanisms of cricket batting expertise. Issues such as skill measurement, practice design, ball machines, skill transfer, the impact of Twenty/20 cricket, video simulation, and skill decomposition are discussed. The ProBatter ball machine systems are introduced along with suggestions for best practice approaches for coaches when designing batting skill development programmes. PMID- 22303783 TI - Biomechanics and visual-motor control: how it has, is, and will be used to reveal the secrets of hitting a cricket ball. AB - Cricket batting is an incredibly complex task which requires the coordination of full-body movements to successfully hit a fast moving ball. Biomechanical studies on batting have helped to shed light on how this intricate skill may be performed, yet the many different techniques exhibited by batters make the systematic examination of batting difficult. This review seeks to critically evaluate the existing literature examining cricket batting, but doing so by exploring the strong but often neglected relationship between biomechanics and visual-motor control. In three separate sections, the paper seeks to address (i) the different theories of motor control which may help to explain how skilled batters can hit a ball, (ii) strategies used by batters to overcome the (at times excessive) temporal constraints, and (iii) an interpretation from a visual-motor perspective of the prevailing biomechanical data on batting. PMID- 22303784 TI - Hitting a cricket ball: what components of the interceptive action are most linked to expertise? AB - Differences in interceptive skill between highly skilled and lesser skilled cricket batsmen were examined using a batting task that required participants to strike front-foot drive strokes from a machine-projected ball to a specified target. Task difficulty was manipulated by varying the width of the bat (normal, half, and third width) and target accuracy, and quality of bat-ball contact was monitored along with temporal and sequential elements of the hitting action. Analyses revealed that the highly skilled batsmen were distinguishable from less skilled counterparts by their higher accuracy under the normal and half-width bat conditions, significantly earlier initiation and completion of the front-foot stride, greater synchronization of the completion of the front-foot stride with the commencement of the downswing of the bat, and consistent timing of downswing relative to ball bounce and impact. In keeping with studies of other hitting sports, temporal and spatial coupling of the downswing to ball bounce to help minimize temporo-spatial error at the point of interception appeared critical to skilled performance. Implications for the understanding of interception and for coaching practice are briefly discussed. PMID- 22303785 TI - Coordination profiles of the expert field hockey drive according to field roles. AB - The aim of this study was to determine coordination profiles for the field hockey drive. Nine elite female players performed five drives each. They were asked to primarily maximize ball placement accuracy, and secondly to drive with high velocity. An optical motion capture system recorded the displacement of six markers on the joints of the players' arms as they performed the drives, and a radar gun measured the ball velocity after impact. Spatial, temporal, and velocity variables were then established. Discrete relative phases were also established at ball impact to examine medio-lateral and proximo-distal upper-arms coordination. The high standard deviation values in joint kinematics were indicative of inter-individual variability, i.e. several drive solutions. Cluster analysis was thus used and two profiles among the players were identified. For the two profiles, the global coordination pattern of movement (upper-arm coordination) was in-phase for the right arm, and out-of-phase for the left lead arm, suggesting a segmental sequencing. However, differences were noted on local kinematic parameters which led to the following categorization: the 'strong group' for defenders and the 'temporal-effectiveness group' for midfielders and forwards. The results support the value of individual analysis to better interpret and contrast the distinct roles of expert players. PMID- 22303786 TI - The effects of stride technique and pitch location on slo-pitch batting. AB - In slo-pitch softball, the ball is delivered in an arc trajectory with a moderate velocity; hence, batters have time to adjust their stride technique based on the pitched ball location. The purpose of this study was to examine the influence of stride technique and pitched ball location on the mechanics of slo-pitch batting. A two-way ANOVA of two locations of pitch (inside and outside) x three strides (open, parallel, and closed) repeated measure study was conducted in this study. The results showed that the stride technique and pitched ball location did not have a consistent impact on the participants across different batting conditions, so the study recommends slo-pitch batters to explore different stride techniques when striking the ball. Further, to better understand the generalizability of the findings, the results indicated that participants were quite homogeneous as a group. Hence, coaches and educators may apply the findings from this study to other players with similar skill level. PMID- 22303787 TI - Kinetics of the upper limb during table tennis topspin forehands in advanced and intermediate players. AB - The purpose of this study was to determine the significance of mechanical energy generation and transfer in the upper limb in generating the racket speed during table tennis topspin forehands. Nine advanced and eight intermediate table tennis players performed the forehand stroke at maximum effort against light and heavy backspin balls. Five high-speed video cameras operating at 200 fps were used to record the motions of the upper body of the players. The joint forces and torques of the racket arm were determined with inverse dynamics, and the amount of mechanical energy generated and transferred in the arm was determined. The shoulder internal rotation torque exerted by advanced players was significantly larger than that exerted by the intermediate players. Owing to a larger shoulder internal rotation torque, the advanced players transferred mechanical energy from the trunk of the body to the upper arm at a higher rate than the intermediate players could. Regression of the racket speed at ball impact on the energy transfer to the upper arm suggests that increase in the energy transfer may be an important factor for enabling intermediate players to generate a higher racket speed at impact in topspin forehands. PMID- 22303788 TI - Review of tennis serve motion analysis and the biomechanics of three serve types with implications for injury. AB - The tennis serve has the potential for musculoskeletal injury as it is an overhead motion and is performed repetitively during play. Early studies evaluating the biomechanics and injury potential of the tennis serve utilized skin-based marker technologies; however, markerless motion measurement systems have recently become available and have obviated some of the problems associated with the marker-based technology. The late cocking and early acceleration phases of the kinetic chain of the service motion produce the highest internal forces and pose the greatest risk of injury during the service motion. Previous biomechanical data on the tennis serve have primarily focused on the flat serve, with some data on the kick serve, and very little published data elucidating the biomechanics of the slice serve. This review discusses the injury potential of the tennis serve with respect to the four phases of the service motion, the history, and early findings of service motion evaluation, as well as biomechanical data detailing the differences between the three types of serves and how this may relate to injury prevention, rehabilitation, and return to play. PMID- 22303789 TI - Subject-specific computer simulation model for determining elbow loading in one handed tennis backhand groundstrokes. AB - A subject-specific angle-driven computer model of a tennis player, combined with a forward dynamics, equipment-specific computer model of tennis ball-racket impacts, was developed to determine the effect of ball-racket impacts on loading at the elbow for one-handed backhand groundstrokes. Matching subject-specific computer simulations of a typical topspin/slice one-handed backhand groundstroke performed by an elite tennis player were done with root mean square differences between performance and matching simulations of < 0.5 degrees over a 50 ms period starting from ball impact. Simulation results suggest that for similar ball racket impact conditions, the difference in elbow loading for a topspin and slice one-handed backhand groundstroke is relatively small. In this study, the relatively small differences in elbow loading may be due to comparable angle-time histories at the wrist and elbow joints with the major kinematic differences occurring at the shoulder. Using a subject-specific angle-driven computer model combined with a forward dynamics, equipment-specific computer model of tennis ball-racket impacts allows peak internal loading, net impulse, and shock due to ball-racket impact to be calculated which would not otherwise be possible without impractical invasive techniques. This study provides a basis for further investigation of the factors that may increase elbow loading during tennis strokes. PMID- 22303790 TI - Serving to different locations: set-up, toss, and racket kinematics of the professional tennis serve. AB - The serve, as the most important stroke in tennis, has attracted considerable biomechanical interest. Of its component parts, the swing has received disproportionate research attention and consequently, little is known regarding toss kinematics. Indeed, the age-old question of whether players serve to different parts of the court from the same toss remains unanswered. Six right handed professionally ranked players hit first serves (FSs) and second serves (SSs) to three 2 x 1 m target areas reflecting the landing locations of T, body and wide serves, respectively, on the deuce court. A 22 camera, 250 Hz VICON MX motion analysis system captured racket, ball, foot, and h and kinematics. Repeated measures ANOVAs assessed within-player differences in foot, racket, and ball kinematics within the FS and SS as a function of landing location. The positions of the front foot, ball zenith, and ball impact were significantly different in the FS, while kinematics across all SS were consistent. Front foot position was closer to the centre mark in the T FS and players impacted the ball further left in the wide FS compared to the T FS. This study discusses the findings in the context of the development of the serve as well as potential implications for the return. PMID- 22303791 TI - Tennis forehand kinematics change as post-impact ball speed is altered. AB - Peak joint angles and joint angular velocities were evaluated for varying speed forehands in an attempt to better understand what kinematic variables are most closely related to increases in post-impact ball velocity above 50% of maximal effort. High-speed video was used to measure three-dimensional motion for 12 highly skilled tennis players who performed forehands at three different post impact ball speeds: fast (42.7 +/- 3.8 m/s), medium (32.1 +/- 2.9 m/s), and slow (21.4 +/- 2.0 m/s). Several dominant-side peak joint angles (prior to ball impact) increased as post-impact ball speed increased from slow to fast: wrist extension (16%), trunk rotation (28%), hip flexion (38%), knee flexion (27%), and dorsiflexion (5%). Between the aforementioned peak joint angles and ball impact, dominant-side peak angular velocities increased as ball speed increased from slow to fast: peak wrist flexion (118%), elbow flexion (176%), trunk rotation (99%), hip extension (143%), knee extension (56%), and plantarflexion (87%). Most kinematic variables changed as forehand ball speed changed; however, some variables changed more than others, indicating that range of motion and angular velocity for some joints may be more closely related to post-impact ball speed than for other joints. PMID- 22303792 TI - Sudden death caused by aortic dissection in a patient with polycystic kidney disease. AB - A 43-year-old man presented at the emergency medical unit with chest pain. The results of a clinical examination were normal, apart from sternum pain (without radiation) on palpation. The patient had no respiratory problems and the pain was relieved by paracetamol. The electrocardiogram, laboratory tests and chest X-ray were normal. However, the man was found dead the next morning. In the autopsy, we noted the presence of haemopericardium, aortic dissection (starting from the vessel's origin and extended to the aortic arch and on through the diaphragm), polycystic kidney disease and liver cysts. In adult autosomal dominant polycystic kidney disease (ADPKD) patients, the main causes of death are ruptured intracerebral aneurysms, coronary artery disease, congestive heart failure, valvular heart disease and ruptured abdominal aortic aneurysms. Aortic dissection is considered to be rare cause of sudden death in ADPKD sufferers. ADPKD can have serious consequences for the vascular system. The families of confirmed ADPKD sufferers must be informed and screened as early as possible, in order to prevent renal and cardiovascular complications. PMID- 22303793 TI - A boy with classical Rubinstein-Taybi syndrome but no detectable mutation in the CREBBP and EP300 genes. AB - Rubinstein-Taybi syndrome (RTS) is a rare autosomal dominant genetic disorder and is characterized by mental retardation, distinctive facial features, broad and often angulated thumbs and great toes. We report on a 7 year old boy with classical Rubinstein-Taybi syndrome. His facial and clinical features were very typical, including broad thumbs with radial angulation and broad great toes. Rigorous genetic analysis of the CREBBP and EP300 genes using DNA sequencing and multiple ligation-dependent probe amplification (MLPA) revealed no causative mutation in this boy, only a hitherto unreported but paternally inherited heterozygous sequence alteration, c.506 1+9C>T in IVS 30-31, which most likely represents a normal variant (NetGene 2 splice prediction software). We question if this boy could have a hitherto undetectable mutation type. PMID- 22303794 TI - Unusual presentation of biliary atresia splenic malformation syndrome with autosomal dominant hypospadias. AB - Biliary atresia is associated with polysplenia in 2-10% of cases and is defined as Biliary Atresia Splenic Malformation syndrome (BASM). The main features of BASM syndrome include extrahepatic biliary atresia and polysplenia besides the characteristic findings of laterality anomalies, cardiac anomalies, intraabdominal vascular anomalies, pancreatic anomalies and malrotation. Here we present a 6-month-old male patient with BASM having atrial septal defect, umblical hernia, inguinal hernia, and hypospadias. Clinical history revealed that his father also had hypospadias which showed a rare form of autosomal dominant inheritance. The karyotype was normal and the molecular analysis of CFC1 gene revealed no mutation. We emphasize the importance of a detailed physical examination in cases with BASM. PMID- 22303795 TI - 8.6Mb interstitial deletion of chromosome 4q13.3q21.23 in a boy with cognitive impairment, short stature, hearing loss, skeletal abnormalities and facial dysmorphism. AB - We describe a 16-year-old boy with an 8.6Mb interstitial deletion of chromosome 4q 13.3q21.23 identified by oligo array-CGH. The patient presents psychomotor developmental delay, absent speech, marked progressive growth restriction, hearing loss, skeletal defects and minor facial anomalies. The patient required surgical treatment for cleft lip and palate, bilateral cryptorchidism and a neurofibroma. The analysis of the presented patient against previously published cases allowed us to expand further on the phenotype and to reevaluate previously proposed critical overlapping region at 4q21. As an addition to PRKG2 and RASGEFIB genes, we propose to include BMP3 gene as the principal determinant of the observed common phenotype. BMP3 haploinsufficiency appears to be causative of hearing loss and peculiar skeletal abnormalities including hemivertebrae and brachydactyly. PMID- 22303796 TI - Femoral hypoplasia-unusual facies syndrome in a black African infant. AB - The femoral hypoplasia-unusual facies syndrome is a very rare association of femora and facial abnormalities. The most common features include hypoplasia of the femora and a characteristic facies with a short nose, long philtrum, thin upper lip and micrognathia. Maternal diabetes mellitus has been mainly identified as the causal agent. We reported the first case in a black African and discuss prenatal diagnosis and aetiology. PMID- 22303797 TI - Sudden vision loss in a mucopolysaccharidosis I patient receiving enzyme replacement therapy. AB - A 25-year-old female was referred for short stature and joint deformities. Except for previous corneal transplantation, her medical history was unremarkable. Initial physical examination revealed the presence of a coarse facies, short neck, kyphosis, restricted joint movements and deformities, and cardiac murmur besides a normal intellect. Urine glycosaminoglycan levels were high, and blood enzyme assay indicated significantly low alpha-L-iduronidase levels. Mucopolysaccharidosis I (MPS I) was diagnosed and prompted the onset of enzyme replacement therapy (ERT), which significantly improved articular complaints, while cardiac pathology remained stable. At the eighteenth month of ERT, sudden vision loss developed. She spontaneously recovered her vision in a month. MPS I is a progressive disease, in which tissue accummulation of heparan and dermatan sulphate result from defective activity or lack of alpha-L-iduronidase. ERT in MPS I usually presents favourable outcomes or at least stabilization of symptoms. This present case qualifies as the first report ofa MPS I patient developing sudden vision loss under ERT. We suggest that further research studies are warranted for defining the efficiency and possible limitations of ERT. PMID- 22303798 TI - The first case of primary alpha-sarcoglycanopathy identified in Albania, in two siblings with homozygous alpha-sarcoglycan mutation. AB - Limb-girdle muscular dystrophy type 2D (LGMD2D) is caused by autosomal recessive mutations in the alpha-sarcoglycan gene. The clinical, biochemical, histological, imunohistochemical and molecular genetic data in 2 Albanian siblings with LGMD2D (adhalinopathy or alpha-sarcoglycanopathy) are presented and the resemblance with Duchenne muscular dystrophy (DMD) is discussed. Both siblings had very high level of CK and a negative molecular test for DMD deletions and duplications. The muscle biopsy showed dystrophic features as well as deficiency in two different proteins, the Gamma sarcoglycan protein (-SG) and the Alpha -SG protein (-SG). DNA analysis demonstrated homozygosity for a pathogenic point mutation (574C>T) in the alpha-sarcoglycan gene, confirming the diagnosis of limb-girdle muscular dystrophy type 2D. We believe it is the first confirmed case of primary alpha sarcoglycanopathy identified in Albania which support the assumption of a wide geographic prevalence of severe childhood onset of autosomal recessive muscular dystrophy, We show that muscle biopsy and DNA diagnosis remains the most sensitive and specific method for differential diagnosis. PMID- 22303799 TI - Mucocutaneous disorders in children with down syndrome: case-controlled study. AB - OBJECTIVE: Down's syndrome is the most frequent chromosomal anomaly that can affect a multiple organ systems, including skin. In this study, we compared the frequency of mucocutaneous disorders in children with Down's syndrome with normal children. METHODS: We recruited fifty children with Down's syndrome and 50 healthy children as a control in our study. Mucocutaneous abnormalities were examined in both groups. FUNDINGS: Of 50 patients, 22 were girls and 28 were boys. The skin findings such as xerosis and Mongolian spots were the most frequently seen in the patients with Down's syndrome. Seborrheic dermatitis, cheilitis and fissured tongue were seen frequently, as well. The rare findings were plantar hyperkeratosis, alopecia areata, geographic tongue, cafe-au-lait macula, livedo reticularis, cutaneous infections, pityriasis capitis simplex, cutis marmorata, neurotic excoriation, trichotillomania, keratosis pilaris and diaper dermatitis. No mucocutaneous finding was seen in 16 patients. The prevalence of the skin disorders including Mongolian spot, seborrheic dermatitis, cheilitis, fissured tongue was significantly higher in patients with Down syndrome than normal individuals (p<0.05). CONCLUSION: Therefore, large-scaled epidemiological studies covering the entire population are needed. We believe that these studies could provide better understanding the dermatological diseases in children with Down's syndrome that would help to practitioners to treat these problems. PMID- 22303800 TI - Alstrom syndrome with acanthosis nigricans: a case report and literature review. AB - Alstrom syndrome (AS) is a very rare autosomal recessively inherited disorder that can lead to infantile-onset dilated cardiomyopathy, blindness, hearing impairment, obesity, diabetes, hepatic and renal dysfunction. AS is caused by mutations in the ALMS1 gene, which is located at chromosome 2p13. The life span of patients with AS rarely goes beyond an age of 40 years. There is no specific therapy for AS, but early diagnosis and intervention may moderate the progression of the disease and may improve the length and quality of the patient's life. We report a 10 year-old boy presenting with Alstrom Syndrome and acanthosis nigricans. PMID- 22303801 TI - Opinions of Turkish physicians towards termination of pregnancy for fetal disorders. AB - Termination of pregnancy (ToP) raises ethical dilemmas. Although ToP for fetal disorders is commonly approved by health professionals, their opinions and attitudes are influenced by a diversity of cultural contexts. The aim of the study is to investigate Turkish physicians' opinions on ToP for fetal disease and the hypothesis is that their opinions are influenced by whether they face any disabilities of affected children or not. We aimed to survey by a questionnaire the opinions of Turkish physicians towards ToP for untreatable fetal disorders. A group of 250 subjects was included in the study. Physicians' approval of parents' decision for ToP was higher for disorders that they encounter more frequently during their daily work. Their opinions were not statistically different when compared for gender and marital status, however, having children of their own caused significant differences for some of the disorders. Approximately 65% of the participants responded that families alone should have the right to decide on ToP. The results confirm that health professionals may have differences in perception of severity of diseases, based on their clinical experience. Physicians encountering affected children more likely approve ToP for that particular disease. PMID- 22303802 TI - Klippel-Feil syndrome and Dandy-Walker malformation. AB - The Klippel-Feil deformity is a complex of osseous and visceral anomalies, which include low hairline, platybasia, fused cervical vertebrae with a short neck, and deafness. Associated central nervous system abnormalities include occipital cephalocele, Chiari I malformation, syrinx, microcephaly, and hydrocephalus. Herein, we report a case with Klippel-Feil syndrome and Dandy-Walker malformation. PMID- 22303803 TI - A severely mental and motor retarded boy with monosomy 9pter-->p22 trisomy 10q26- >qter due to paternal reciprocal translocation 46,XY,t(9;10)(p23;q26). AB - We report on a twenty-two months old male patient with hypotonia, mental and motor retardation and trigonocephaly. Standard GTG banding chromosomal analysis (from metaphyses of a periferal blood lymphocyte culture) showed 46,XY, der(9) monosomy 9pter-->p22, trisomy 10q26--> qter karyotype. This unbalanced translocation resulted from the father's t(9,10) (p22;p26) karyotype. Deletions of the terminal part of 9p and partial trisomy of chromosome 10q are rare chromosomal disorders. To our knowledge, this is the first case report in the literature of a deletion of 9pter-->p22.3 and a duplication of 10q26-->qter. We assume that the clinical anomalies are due to der(9) monosomy 9pter-->p22, trisomy 10q-->26qter. PMID- 22303804 TI - Pure interstitial duplication of chromosome 7q (7q31.2-->q33) in a 4-year-old girl with growth restriction, short stature, speech delay and intellectual disability. AB - We report the cytogenetic and molecular characterization of a 22.3-Mb pure interstitial duplication of chromosome 7q, dup(7)(q31.2-->q33) in a 4-year-old girl with growth restriction, short stature, speech delay, inguinal hernia, strabismus and intellectual disability. We speculate that the gene dosage increase effect of the ING3 and LEP genes may be partially responsible for the phenotype of growth restriction and short stature in this patient. PMID- 22303805 TI - A 20.5-Mb germline deletion of 13q13.1-->q14.3 and somatic mutations of the RB1 gene in an 8-year-old girl with unilateral retinoblastoma, developmental delay and mental retardation. PMID- 22303806 TI - Cornelia de Lange syndrome in a preterm infant presenting with coarctation of aorta and perimembranous ventricular septal defect. PMID- 22303807 TI - Purification, cloning, and immunological characterization of arginine kinase, a novel allergen of Octopus fangsiao. AB - Arginine kinase (AK) is an important enzyme participating in energy metabolism in invertebrates, but, to date, there have been no reports that AK from octopus is an allergen. In this study, octopus AK was purified, and its molecular biological, immunological, and physicochemical characterizations were analyzed. The results showed that octopus AK was purified and confirmed by mass spectrometry for the first time, and its molecular mass was 38 kDa. The full length gene sequence of octopus AK encompassed 1209 bp and was predicted to encode a protein with 348 amino acid residues. The homology of octopus AK and crustacean AK was about 54%, but the similarity between their three-dimensional structures was high. Octopus AK could react with mouse anti-shrimp AK and rabbit anti-crab AK polyclonal antibody singly. Octopus AK could also react with specific IgE of the sera from octopus-allergic patients effectively, whereas crab AK could inhibit the reaction between them. Finally, the IgE-binding activity of octopus AK could be reduced in the processes of thermal or acid-alkali treatment. In summary, AK was identified as a novel allergen in octopus, which had a sensitizing ability similar to that of crustacean AK. This is significant in allergy diagnosis and the treatment of octopus-allergic disorders. PMID- 22303808 TI - Oxidative and non-oxidative DNA damage and cardiovascular disease. AB - Evidence for the association of DNA damage with cardiovascular disease has been obtained from in vitro cell culture models, experimental cardiovascular disease and analysis of samples obtained from humans with disease. There is general acceptance that several factors associated with the risk of developing cardiovascular disease cause oxidative damage to DNA in cell culture models with both nuclear and mitochondrial DNA as targets. Moreover, evidence obtained over the past 10 years points to a possible mechanistic role for DNA damage in experimental atherosclerosis culminating in recent studies challenging the assumption that DNA damage is merely a biomarker of the disease process. This kind of mechanistic insight provides a renewed impetus for further studies in this area. PMID- 22303809 TI - Polyamidomine dendrimers: an excellent drug carrier for improving the solubility and bioavailability of puerarin. AB - The potential of polyamidoamine (PAMAM) dendrimers as solubility enhancers and oral drug delivery system was well known. Herein, we investigated the possibility of PAMAM dendrimers for promoting the solubility and oral bioavailability of puerarin. In the present study, the effect of PAMAM dendrimers with different generations (G1.5, G2, G2.5, and G3) on the solubility of puerarin was evaluated at different concentrations and pH conditions. Further more, the puerarin-G2 dendrimer complex was conducted for the in vitro hemolytic toxicity studies and pharmacokinetics studies in rats. The solubility of puerarin was significantly higher in the presence of the full generation dendrimers (e.g. G2 and G3). No significant hemolysis was observed on erythrocytes (G2, 0-2.5 mg/mL) in the hemolytic toxicity studies. The pharmacokinetics parameters Tmax, Cmax, and AUC0 8 h of puerarin suspension solution and puerarin-G2 dendrimer complex solution were 0.76 h, 1.50 ug/mL, 7.33 ug.h/mL and 0.33 h, 6.49 ug/mL, 14.02 ug.h/mL, respectively. These studies demonstrate that PAMAM dendrimers may be a promising strategy for peroral delivery of puerarin. PMID- 22303810 TI - Variations in structures, processes and outcomes of community mental health teams for older people: a systematic review of the literature. AB - OBJECTIVES: In the UK and elsewhere, specialist community mental health teams (CMHTs) are central to the provision of comprehensive services for older people with mental ill health. Recent guidance documents suggest a core set of attributes that such teams should encompass. This article reports on a systematic literature review undertaken to collate existing evidence regarding the structures and processes of CMHTs for older people and to evaluate evidence linking approaches to effectiveness. METHOD: Relevant publications were identified via systematic searches, both electronic and manual. Searches were limited to the UK for descriptions of organisation and practice but included international literature where comparisons between different CMHT arrangements were evaluated. Empirical, peer-reviewed studies from 1989 onward were included, extended to non peer-reviewed nationally or regionally representative reports, published after 1998, for the descriptive element. RESULTS: Forty-five studies met inclusion criteria of which seven provided comparative outcome data. All but one were UK based. The most robust evidence related to research conducted in exemplar teams. Limited evidence was found regarding the effectiveness of many of the core attributes recommended in policy directives although their presence was reported in much of the literature. CONCLUSIONS: The contrast between presentation and evaluation of attributes is stark. Whilst some gaps can be filled from related fields, further research is required that moves beyond description to evaluation of the impact of team design on service user outcomes in order to inform future policy directives and practice guidance. A framework for an evidence-based model of CMHTs for older people is provided. PMID- 22303811 TI - Fluoride in drinking water and defluoridation of water. PMID- 22303812 TI - Trade-offs between offspring fitness and future reproduction of adult female black brent. AB - 1. Successful reproduction requires numerous decisions, and some of which may require trade-offs between current and future reproduction. We studied effects of choice of foraging patches on gosling growth and future breeding by mothers in black brent (Branta bernicla nigricans) geese. 2. Specific foraging areas consistently produced high-quality goslings over 21 years. We found a consistent ranking of gosling mass, corrected for age, across brood rearing areas (BRAs) and years [Akaike model weights, Sigmaw(i) = 1.00 for models including additive effects of BRA and year]. Growth of goslings largely determines their future fitness, so areas where goslings grew most rapidly also produced goslings with the highest mean fitness. 3. We used a multistate robust design capture-mark recapture approach to estimate the probability of transitioning from a breeding state to a non-breeding (unobservable) state as a function of quality of BRA. 4. In the best supported model, transition from a breeding state to a non-breeding state was positively related to gosling growth rates across BRAs. Thus, future reproduction was lower for females using BRAs that produced higher-quality goslings. Our results are consistent with trade-offs by individual brent between fitness of their current offspring and their own reproductive value. PMID- 22303813 TI - Ultra acidic strong cation exchange enabling the efficient enrichment of basic phosphopeptides. AB - We present a straightforward method to enrich phosphopeptides with multiple basic residues, an under-represented class in common enrichment strategies. Our method is based on a two-dimensional strong cation exchange (SCX) strategy, operating at two different acidic pHs, enabling both separation and enrichment of different classes of phosphopeptides. The principle of enrichment is based on the change of net charge of phosphorylated peptides under strong acidic conditions in the second SCX, whereas the net charge of regular peptides remains unchanged, thus enabling separation based on net charge. Application of our tandem SCX approach to a modest amount of human cells allowed the identification of over 10,000 unique "basic" phosphopeptides of which many represent putative targets of basophilic kinases. PMID- 22303814 TI - Clinical and immunomodulatory effects of toceranib combined with low-dose cyclophosphamide in dogs with cancer. AB - BACKGROUND: Tyrosine kinase inhibitors (TKIs) and metronomic dosing of cyclophosphamide (CYC) can improve tumor control by suppression of regulatory T cells (Treg) and restoration of T cell-mediated immune responses in mice and humans. The immunomodulatory effects of the TKI toceranib, as a single agent or in combination with metronomic CYC, have not been previously investigated in dogs. HYPOTHESIS: The primary objectives of this study were to determine the effects of toceranib and metronomic CYC treatment on lymphocyte subsets including Treg and on interferon-gamma (IFN-gamma) secretion in dogs with cancer. We hypothesized that toceranib would selectively decrease Treg numbers and increase IFN-gamma production and that addition of CYC would further enhance these effects. ANIMALS: Fifteen client-owned dogs with advanced tumors were entered into a prospective clinical trial. METHODS: Dogs received toceranib at 2.75 mg/kg once every other day. After 2 weeks, oral CYC was added at 15 mg/m(2) daily. Numbers of Treg and lymphocyte subsets were measured in blood by flow cytometry during the 8-week study period. Serum concentrations of IFN-gamma were measured by ELISA. RESULTS: Administration of toceranib significantly decreased the number and percentage of Treg in the peripheral blood of dogs with cancer. Dogs receiving toceranib and CYC demonstrated a significant increase in serum concentrations of IFN-gamma, which was inversely correlated with Treg numbers after 6 weeks of combination treatment. CONCLUSIONS: In addition to antitumor effects, these data support further investigations into the immunomodulatory effects of toceranib, administered alone or in combination with CYC in dogs with cancer. PMID- 22303815 TI - Testing the limits of long-distance learning: learning beyond a three-segment window. AB - Traditional flat-structured bigram and trigram models of phonotactics are useful because they capture a large number of facts about phonological processes. Additionally, these models predict that local interactions should be easier to learn than long-distance ones because long-distance dependencies are difficult to capture with these models. Long-distance phonotactic patterns have been observed by linguists in many languages, who have proposed different kinds of models, including feature-based bigram and trigram models, as well as precedence models. Contrary to flat-structured bigram and trigram models, these alternatives capture unbounded dependencies because at an abstract level of representation, the relevant elements are locally dependent, even if they are not adjacent at the observable level. Using an artificial grammar learning paradigm, we provide additional support for these alternative models of phonotactics. Participants in two experiments were exposed to a long-distance consonant-harmony pattern in which the first consonant of a five-syllable word was [s] or [?] ("sh") and triggered a suffix that was either [-su] or [-?u] depending on the sibilant quality of this first consonant. Participants learned this pattern, despite the large distance between the trigger and the target, suggesting that when participants learn long-distance phonological patterns, that pattern is learned without specific reference to distance. PMID- 22303816 TI - Community involvement, planning and coping skills: pilot outcomes of a recreational-therapy intervention for adults with schizophrenia. AB - PURPOSE: The Independence through Community Access and Navigation (I-CAN) intervention was developed to increase community participation in adults with schizophrenia spectrum disorders (SSD) through identification of interest-based recreation activities and supported participation. METHOD: Ten individuals consented to participate in a 10-week pilot intervention. Eight individuals participated in the intervention, during which time they worked with a recreational therapist to identify interest-based recreation activities, develop participation goals and coparticipate with the recreational therapist. At the end of the intervention, seven participants were involved in a semistructured interview to understand their perceptions of the intervention, including its outcomes and effectiveness. Therapists' notes and transcripts from the semistructured interviews were used to understand clients' perception of the intervention. RESULTS: Thematic analyses of seven exit interviews suggested the primary perceived outcomes of the intervention included: increased community involvement; development of planning skills; and the development of coping skills. These were facilitated by the therapeutic relationship between the client and therapist. CONCLUSIONS: This project provides preliminary support for the I CAN as a participant-centered method for individuals with SSD to develop skills in the community. Implications for practice and future research are presented. PMID- 22303817 TI - Au(I)-catalyzed intramolecular hydroamination of the fluorinated N'-aryl-N propargyl amidines: mild conditions for the synthesis of 2-fluoroalkyl imidazole derivatives. AB - The gold(I)-catalyzed synthesis of 2-fluoroalkyl imidazole derivatives was developed. Catalyzed by gold(I), propargyl amidines underwent a 5-exo-dig cyclization to afford 2-fluoroalkyl-5-methyl imidazoles. Also, 2-fluoroalkyl imidazole-5-carbaldehydes were obtained in the presence of NIS. A mechanism investigation manifested the probable process and the carbonyl oxygen derived from O(2). PMID- 22303818 TI - Total and differential leucocyte counts in relation to incidence of stroke subtypes and mortality: a prospective cohort study. AB - OBJECTIVES: Elevated levels of total leucocyte as well as leucocyte subtypes have been associated with increased risk of atherosclerotic disease. Atherosclerosis is an important cause of cerebral infarction, whereas its significance in intracerebral haemorrhage (ICH) is less clear. A small number of prospective studies have revealed the relationship between leucocyte counts and incident stroke, in particular incidence of stroke subtypes. We evaluated the associations between total leucocyte count (TLC) as well as leucocyte subtypes and the incidence of and mortality caused by different stroke subtypes. DESIGN AND SUBJECTS: Of 28 449 participants from the Malmo Diet and Cancer Study, 26 927 stroke-free subjects (mean age at screening, 58 +/- 8 years) were included in a prospective cohort study. The screening period was between 1991 and 1996. Incidence of stroke, 1-year mortality and 1-month case-fatality rate (CFR) were assessed by linkage to local and national registers. Cox regression analysis was used to assess stroke risk and 1-year mortality, and 1-month CFR was assessed by logistic regression analysis. RESULTS: During a follow-up period of 13.6 +/- 3.3 years, 1515 participants had a first-ever stroke (cerebral infarction, n = 1314; ICH, n = 201). After adjustments for other risk factors, TLC and neutrophil count were significantly associated with increased incidence of cerebral infarction (hazards ratio (HR), 1.4; 95% confidence interval (CI), 1.2-1.7 and 1.3; 95% CI, 1.1-1.5, respectively). There was an inverse association between elevated TLC and incident ICH (HR, 0.7; 95% CI, 0.4-0.99). No associations were found between leucocyte counts and mortality for either stroke subtype. CONCLUSION: The results suggest that the relationships with inflammation for ischaemic stroke and ICH are different. PMID- 22303819 TI - Implicit measures of the stereotype content associated with disability. AB - The present research aimed to show that the mixed stereotype content of persons with disability observed at an explicit level does not manifest itself using implicit measures. Two experimental studies were conducted to analyse the stereotype content of persons with a disability at the implicit level. The procedure used in this study was the concept priming paradigm. Furthermore, Study 2 also included an explicit measure. Results show important discrepancies between implicit and explicit measures. At an explicit level, previous work supporting the mixed stereotype content of persons with disability was replicated: participants judged these persons as warmer but less competent than persons without a disability. At an implicit level, a quite different pattern of results emerged: persons with a disability were associated not only with less competence than persons without disability, but also with less warmth. These findings suggest that the mixed pattern between warmth and competence generally observed at an explicit level may be based on societal pressures against prejudice and discrimination. PMID- 22303820 TI - Underuse of aspirin for primary and secondary prevention of cardiovascular disease events in women. AB - BACKGROUND: Evidence-based guidelines for use of aspirin to decrease cardiovascular disease (CVD) events in women are well established. Despite this, aspirin is underused in women. We examined self-reported aspirin use in women for primary and secondary prevention of CVD events, correlates of use, and change in use over time from 2004 to 2009. METHODS: Data from volunteer respondents participating in a web-based CVD risk assessment tool at 127 US healthcare centers were analyzed. Survey questions included information on CVD risk factors, the presence or absence of any form of CVD, diabetes mellitus, and medication usage, including daily aspirin. Logistic regression analyses identified factors associated with aspirin intake. RESULTS: Of the 217,987 women respondents, 29,701 women were recommended to take aspirin based on the guidelines. We found, however, that only 41% of women who meet criteria for primary prevention and 48% of women who meet criteria for secondary prevention report that they take aspirin on a daily basis. The main factors that favored aspirin use were a family history of CVD or high cholesterol. Although aspirin use for secondary prevention did not change between the years 2004 and 2009, there was a significant increase in aspirin use for primary prevention. CONCLUSIONS: These findings confirm that the majority of women for whom aspirin is recommended for primary and secondary prevention of CVD were not following national guidelines. Educational programs for clinicians and women aimed at promoting appropriate use of aspirin is one measure that should improve CVD outcomes in women. PMID- 22303821 TI - Attention deficit hyperactivity symptoms and risky sexual behavior in young adult women. AB - BACKGROUND: This study was undertaken to assess the association between adult attention deficit/hyperactivity disorder (ADHD) symptoms and high-risk sexual behavior. METHODS: This cross-sectional study interviewed 462 low-income women aged 18-30 years. We used the 18-item Adult ADHD Self-Report Scale (ASRS-v1.1) Symptom Checklist to assess ADHD symptoms. Risky sexual behaviors included sex before 15 years of age, risky sex partners in lifetime, number of sex partners in the last 12 months, condom use in the last 12 months, alcohol use before sex in the last 12 months, traded sex in lifetime, and diagnosed with sexually transmitted infection (STI) in lifetime. RESULTS: Mean ADHD symptom score was 19.8 (SD+/-12.9), and summary index of all risky sexual behavior was 1.77 (SD+/ 1.37). Using unadjusted odds ratios (OR), women who endorsed more ADHD symptoms reported engaging in more risky sexual behaviors of all types. However, when multivariable logistic regression was applied adjusting for various sociodemographic covariates, the adjusted ORs remained significant for having risky sex partners and having >=3 sex partners in the prior 12 months. We observed some differences in risky sexual behavior between two domains of ADHD. CONCLUSIONS: The ADHD symptom score appears to be associated with some risky sexual behaviors and deserves further attention. A brief ADHD screening can identify this high-risk group for timely evaluation and safe sex counseling. PMID- 22303822 TI - Penetration of amphiphilic quantum dots through model and cellular plasma membranes. AB - In this work we demonstrate progress in the colloidal synthesis of amphiphilic CdTe nanocrystals stabilized by thiolated PEG oligomers with the aim of facilitating cellular uptake of the particles. High-boiling, good coordinating solvents such as dimethylacetamide and dimethylformamide accelerate the growth of the nanoparticles yielding stable colloids of which photoluminescence maxima can be tuned to cover the region of 540-640 nm with quantum yields of up to 30%. The CdTe nanocrystals capped by thiolated methoxypolyethylene glycol are shown to penetrate through the lipid bilayer of giant unilamellar vesicles and giant plasma membrane vesicles which constitute basic endocytosis-free model membrane systems. Moreover, the penetration of amphiphilic particles through live cell plasma membranes and their ability to escape the endocytic pathway have been demonstrated. PMID- 22303823 TI - Photochemical nature of parietopsin. AB - Parietopsin is a nonvisual green light-sensitive opsin closely related to vertebrate visual opsins and was originally identified in lizard parietal eye photoreceptor cells. To obtain insight into the functional diversity of opsins, we investigated by UV-visible absorption spectroscopy the molecular properties of parietopsin and its mutants exogenously expressed in cultured cells and compared the properties to those of vertebrate and invertebrate visual opsins. Our mutational analysis revealed that the counterion in parietopsin is the glutamic acid (Glu) in the second extracellular loop, corresponding to Glu181 in bovine rhodopsin. This arrangement is characteristic of invertebrate rather than vertebrate visual opsins. The photosensitivity and the molar extinction coefficient of parietopsin were also lower than those of vertebrate visual opsins, features likewise characteristic of invertebrate visual opsins. On the other hand, irradiation of parietopsin yielded meta-I, meta-II, and meta-III intermediates after batho and lumi intermediates, similar to vertebrate visual opsins. The pH-dependent equilibrium profile between meta-I and meta-II intermediates was, however, similar to that between acid and alkaline metarhodopsins in invertebrate visual opsins. Thus, parietopsin behaves as an "evolutionary intermediate" between invertebrate and vertebrate visual opsins. PMID- 22303824 TI - The most convenient and general approach for plasma sample clean-up: multifunction adsorption and supported liquid extraction. PMID- 22303826 TI - US FDA/EMA harmonization of their bioanalytical guidance/guideline and activities of the Global Bioanalytical Consortium. AB - The 2011 annual conference of the American Association of Pharmaceutical Scientists, held in Washington DC, USA, hosted a roundtable entitled: 'Update of the US FDA/European Medicines Agency (EMA) harmonization of their bioanalytical guidance - Global Bioanalytical Consortium activity and impact on small and large molecules.' The roundtable was initiated with a presentation from CT Viswanathan on the history of the revision of the FDA guideline on bioanalytical method validation. It was followed by a presentation by Jan Welink who presented an update on the final European Medicines Agency guideline on bioanalytical method validation with relevance to ongoing harmonization efforts. The final presentation was by Fabio Garofolo on the progress of the Global Bioanalytical Consortium harmonization teams for small and large molecules. Brian Booth and Sam Haidar of the FDA updated the audience on the status of the revision of the FDA bioanalytical guidance. The roundtable was moderated by Stephen Lowes. PMID- 22303827 TI - Incurred sample reanalysis comparison of dried blood spots and plasma samples on the measurement of lopinavir in clinical samples. AB - BACKGROUND: Undoubtedly, incurred sample reanalysis (ISR) will become an integral part of regulated bioanalysis of dried blood spot (DBS) samples. In this article, we report results from an ISR study on DBS specimen and their corresponding plasma samples. Incurred samples were reanalyzed on their concentration of the antiretroviral drug lopinavir (LPV). RESULTS: Bland-Altman comparison plots showed a high degree of agreement between the measurements; 94.7% of observed LPV concentrations were within bias +/-2 SD. Moreover, 73.7% of obtained LPV concentrations from DBS ISR were in good compliance with general acceptance criteria (4-6-20 rule) on ISR testing, while plasma ISR failed on these acceptance criteria due to the low compliance of 10.5%. CONCLUSION: It was demonstrated that plasma ISR testing failed on acceptance criteria while corresponding incurred DBS specimens passed. Furthermore, the current article demonstrates that the stability of the antiretroviral drug LPV was significantly different in both biological matrices. PMID- 22303828 TI - A novel, high-sensitivity and drug-tolerant sandwich immunoassay for the quantitative measurement of circulating proteins. AB - BACKGROUND: Accurate measurement of a total protein target (free plus bound) is essential to optimize dose selection for monoclonal antibody drugs. Herein, we describe a novel sandwich immunoassay format in which the biotherapeutic antibody itself serves as the primary detection antibody. A signal is then generated through the addition of a labeled secondary antibody that recognizes the biotherapeutic antibody. The secondary antibody is conjugated with ruthenium to facilitate electrochemiluminescent analysis. RESULTS: Data are presented from the analysis of two protein biomarkers having disparate size and structure; a 4.5 kDa peptide and a 60 kDa protein. In both cases, validated, highly specific assays were developed and shown to be tolerant to elevated levels of the therapeutic monoclonal antibody in question. CONCLUSION: Our novel format allows drug tolerant measurement of soluble protein biomarkers targeted by monoclonal antibodies when only two independent epitopes for antibody binding are available and one is recognized by the therapeutic antibody. PMID- 22303829 TI - Automated supported liquid extraction using 2D barcode processing for routine toxicokinetic portfolio support. AB - BACKGROUND: A new bioanalytical sample preparation approach has been developed to enhance the efficiency, reduce errors and improve the data quality supporting routine toxicokinetic (TK) study samples analysis, via the implementation of 2D barcode processing coupled with fully automated supported liquid extraction (SLE). RESULTS: A fully automated SLE was validated and used to determine TK drug concentrations of over 500 unknown samples via 2D barcode processing. Assay performance calculated from a total of 291 quality control samples over the period of validation through sample analysis demonstrated inter-day precision and accuracy within 10 and 7.3%, respectively. CONCLUSION: A new logistical approach implementing the use of 2D barcodes and automated SLE demonstrates the potential of a new methodology for the routine bioanalytical support of TK study sample analysis. PMID- 22303830 TI - In vitro evaluation of the potential for drug-induced toxicity based on (35)S labeled glutathione adduct formation and daily dose. AB - BACKGROUND: Drug-induced toxicity such as idiosyncratic drug toxicity is believed to be reduced when either reactive metabolite formation or exposure to a drug is minimized. The objective of the present study was therefore to clarify the relationship between the daily doses, the formation rates of reactive metabolite adduct with (35)S-glutathione (RM-GS) and the safety profiles of compounds. RESULTS: The RM-GS formation rates for 113 test compounds were determined by incubation with human liver microsomes, and the test compounds were classified into three categories of safe, warning and withdrawn/black box warning. A total of 23 out of 28 withdrawn/black box warning drugs showed both a RM-GS formation rate of over 1 pmol/30 min/mg protein and a dose of over 100 mg. CONCLUSION: These results suggest that when compounds are plotted in this region, the compounds would have a relatively high idiosyncratic drug toxicity potential. PMID- 22303831 TI - Matrix effect and recovery terminology issues in regulated drug bioanalysis. AB - Understanding the meaning of the terms used in the bioanalytical method validation guidance is essential for practitioners to implement best practice. However, terms that have several meanings or that have different interpretations exist within bioanalysis, and this may give rise to differing practices. In this perspective we discuss an important but often confusing term - 'matrix effect (ME)' - in regulated drug bioanalysis. The ME can be interpreted as either the ionization change or the measurement bias of the method caused by the nonanalyte matrix. The ME definition dilemma makes its evaluation challenging. The matrix factor is currently used as a standard method for evaluation of ionization changes caused by the matrix in MS-based methods. Standard additions to pre extraction samples have been suggested to evaluate the overall effects of a matrix from different sources on the analytical system, because it covers ionization variation and extraction recovery variation. We also provide our personal views on the term 'recovery'. PMID- 22303832 TI - Replacing immunoassays with tryptic digestion-peptide immunoaffinity enrichment and LC-MS/MS. AB - For decades, immunoassays have provided the framework for protein biomarker studies in clinical medicine and in therapeutic monitoring for drug development. At the same time, investigators have uncovered many issues that make immunoassays unreliable in many human serum and plasma samples. LC-MS/MS after tryptic digestion of proteins is potentially an attractive solution, but the sensitivity of the method is not sufficient to measure many important low-abundance proteins directly. The use of antipeptide antibodies to immunoenrich peptides of interest can improve the sensitivity of the approach, greatly simplify the matrix enabling shortened chromatographic runs, and facilitate the multiplexed quantification of analytes, which could reduce the costs of quantitative protein measurements in complex specimens. We provide an overview of the method and the steps needed to develop an assay. In addition, we review the efforts to make this method generally more applicable. PMID- 22303833 TI - Methods for the analysis of nonbenzodiazepine hypnotic drugs in biological matrices. AB - Zopiclone, zolpidem and zaleplon (Z-drugs) are nonbenzodiazepine hypnotic drugs that are used for the treatment of insomnia. These drugs were developed with the intent to overcome some disadvantages of benzodiazepines, such as dependence and next day sedation. In general, the nonbenzodiazepine hypnotic drugs are administered in oral doses daily and are widely biotransformed in the body. A large number of analytical methods based on chromatographic and electrophoretic techniques for the quantification of Z-drugs and their metabolites in biological matrices have been reported. In this review, the bioanalytical methods for Z drugs were reviewed with the focus placed on sample preparation procedures and the separation techniques used. Furthermore, as these drugs are also reported as drugs of abuse or in drug-facilitated crime, screening methods that simultaneously cover these drugs and also other drugs of abuse were included in this review. PMID- 22303834 TI - Validation and verification of measurement methods in clinical chemistry. AB - The present overview of validation and verification procedures in clinical chemistry focuses on the use of harmonized concepts and nomenclature, fitness-for purpose evaluations and procedures for minimizing overall measurement and diagnostic uncertainty. The need for mutually accepted validation procedures in all fields of bioanalysis becomes obvious when they implement international accreditation and certification standards or their equivalents. The guide on bioanalytical method validation published by the US FDA in 2001 represents a sensible compromise between thoroughness and cost-effectiveness. Lacking comprehensive international agreements in the field, this document has also been successfully adapted in other fields of bioanalysis. European and international efforts aiming for consensus in the entire field of bioanalysis are currently being made. Manufacturers of highly automated in vitro diagnostic methods provide the majority of measurement methods used in unmodified in clinical chemistry. Validated by the manufacturers for their intended use and fitness-for-purpose, they need to be verified in the circumstances of the end-users. As yet, there is unfortunately no general agreement on the extent of the verification procedures needed. PMID- 22303835 TI - Quantitative analysis in magnetic resonance spectroscopy: from metabolic profiling to in vivo biomarkers. AB - Nuclear magnetic resonance spectroscopy (called NMR for ex vivo techniques and MRS for in vivo techniques) has become a useful analytical and diagnostic tool in biomedicine. In the past two decades, an MR-based spectroscopic approach for translational and clinical research has emerged that allows for biochemical characterization of the tissue of interest either ex vivo (NMR-based metabolomics) or in vivo (localized MRS-single voxel or multivoxel-spectroscopic imaging). The greatest advantages of MRS techniques are their ability to detect multiple tissue-specific metabolites in a single experiment, their quantitative nature and translational component (in vitro/ex vivo-discovered metabolic biomarkers can be translated into noninvasive spectroscopic imaging protocols). Disadvantages of MRS include low sensitivity and spectral resolution and, in case of NMR-metabolomics, metabolite degradation and incomplete recovery in processed samples. In vivo MRS has worse spectral resolution than ex vivo high-resolution NMR due to the inherently wider lines of metabolites in vivo and the difficulty of using traditional line-narrowing methods (e.g., sample spinning). It also suffers from poor time-resolution, therefore offering fewer metabolic biomarkers to be followed in vivo. In the present review article, we provide considerations for establishing reliable protocols (both in vivo and ex vivo) for metabolite detection, recovery and quantification from in vivo and ex vivo MR spectra. PMID- 22303837 TI - Boronate-mediated biologic delivery. AB - Inefficient cellular delivery limits the landscape of macromolecular drugs. Boronic acids readily form boronate esters with the 1,2- and 1,3-diols of saccharides, such as those that coat the surface of mammalian cells. Here pendant boronic acids are shown to enhance the cytosolic delivery of a protein toxin. Thus, boronates are a noncationic carrier that can deliver a polar macromolecule into mammalian cells. PMID- 22303838 TI - Functionalization of magnetic nanoparticles with amphiphilic block copolymers: self-assembled thermoresponsive submicrometer particles. AB - For the first time the four block copolymers derived from 1-alkyl[2 (acryloyloxy)ethyl]dimethylammonium bromides with hexyl (ADA) or cetyl (ADHA) groups and 2-hydroxyethylacrylate (HEA) or N-isopropylacrylamide (NIPAM) were synthesized and employed for functionalization of monodisperse iron oxide nanoparticles (NPs). The polyADA (pADA) or polyADHA (pADHA) block consists of long hydrophobic tails (C(6) or C(16)) connected to a positively charged quaternary ammonium group, making this block amphiphilic. The second block was either fully hydrophilic (pHEA) or thermoresponsive (pNIPAM). The dependence of the NP coating on the length of the hydrophobic tail in the amphiphilic block, the composition of the hydrophilic block, and the NP sizes have been studied. Unusual self-assembling of iron oxide NPs into well-defined composite submicrometer particles was observed for pADHA-b-pNIPAM in the wide range of concentrations (at the pADHA repeating unit concentrations of 0.065 * 10(-2)-2.91 * 10(-2) mmol/mL per 1 mg/mL NPs) but only two concentrations, 1.62 * 10(-2) and 1.94 * 10(-2) mmol/mL, led to regular spherical particles. The thermoresponsive behavior of these composite particles was tested using zeta-potential and dynamic light scattering measurements, while the morphology of particles was characterized by transmission electron microscopy. Coating of NPs with pADHA-b pHEA results in the formation of individually coated NPs. The different composite particle morphologies are explained by different properties of pHEA and pNIPAM. It is demonstrated that the composite particles based on pADHA-b-pNIPAM are responsive to a magnetic field and can be recommended as magnetic stoppers in biorelated membrane separations. The incorporation of Pd species in submicrometer particles makes them promising candidates for catalytic applications as magnetically recoverable catalysts with a high magnetic response. PMID- 22303839 TI - A comprehensive review of telehealth for pain management: where we are and the way ahead. AB - Pain is generally undertreated in the United States, owing to a number of barriers including geographic distance from specialty treatment providers; functional disability that limits mobility; treatment-related stigma; economic limitations; and educational barriers. Pain undertreatment exacerbates pain chronicity and emotional disruption that can significantly erode a pain patient's quality of life, and there is widespread agreement that pain care must evolve to address this significant problem. The growing field of telehealth (defined for the purposes of this paper as technology that allows for distance interaction between providers and/or patients) offers a novel opportunity to expand pain assessment, consultation, and treatment services beyond the walls of the specialty pain clinic, but there is limited availability of resources describing how to best use this technology to improve access to care. A recent literature review (September 2011) using universally endorsed MeSH search criteria revealed only 32 MEDLINE references focusing on telehealth for pain. This is surprising in light of the very large number of references covering telehealth (14,164 references) and pain (104,564 references), respectively. Of the studies available, there are very few randomized trials of telehealth pain care and only one general overview of e-health and chronic pain, which dedicates just a few paragraphs to telehealth. This manuscript represents one of the first comprehensive reviews of the current state of telehealth and pain management research and practice. The goals are to provide a rationale for the potential benefit of telehealth-based pain management services; describe the various applications of telehealth technology for pain management; orient the reader to cost models for telehealth; present examples of services in place; and offer recommendations for future research based on the current state of knowledge. PMID- 22303840 TI - Gonadotrophin-releasing hormone analogues and endometriosis: current strategies and new insights. AB - BACKGROUND: Endometriosis is an estrogen-dependent chronic inflammatory disease affecting 5% to 10% of women in reproductive age and has been reported also in adolescents. Its main clinical presentations are chronic pelvic pain and infertility. OBJECTIVE: To provide a comprehensive review of the recently published data concerning the mechanism of action of gonadotrophin-releasing hormone analogues (GnRHas) as well as to analyze their role in the management of endometriosis-associated pain and infertility in addition to its value in adolescent cases. Furthermore, to provide practical recommendations and new insights based on the best available information. METHODS: Systematic search was performed of the Cochrane Library and Medical Literature Analysis and Retrieval System Online database looking for the different trials, reviews and various guidelines relating to GnRHas usage in the management of endometriosis-associated pain, infertility and in adolescent cases. RESULTS: From a pathophysiological perspective, there is a growing scientific evidence that GnRHas exert its therapeutic effects by their classical pituitary downregulation and via a direct effect on the endometrial cells themselves. Accordingly, they represent an important medical option for the management of different aspects of this enigmatic disease. CONCLUSION: GnRHas have a valuable strategic role in treatment of endometriosis-associated pain and infertility as well as in adolescents above 16 years. PMID- 22303841 TI - A systematic review of the impact of foreign postings on accompanying spouses of military personnel. AB - Military spouses frequently cope with separation, but limited research reviewing the impact of an overseas relocation when a spouse accompanies their serving husband/wife has been conducted. A search for studies reviewing the impact of foreign postings on these accompanying spouses was undertaken utilizing 12 databases and other resources. Ultimately, 12 studies were analyzed and four key themes produced: functioning of a military family on an international posting, loss, wellbeing and support. Overall, additional stressors are associated with an overseas posting and experiences are specific to an individual and their circumstances. Further research is required to examine the potential relationship between a spouse's experiences overseas and the impact on their health and wellbeing. This would help to identify possible areas of health care provision and support necessary to maximize a military spouse's experience. PMID- 22303842 TI - Biomarkers of oxidative stress and cancer: from chemistry, biology to clinical applications and personalized therapy. PMID- 22303843 TI - Performance and interaction anxiety: specific relationships with other- and self evaluation concerns. AB - This study examines whether performance anxiety (PA) is specifically associated with other-evaluation concerns and interaction anxiety (IA) with self-evaluation concerns. Individuals with public speaking fears and high levels of PA or IA were distinguishable from nonanxious controls on measures taken during a public speaking challenge. In addition, high PA individuals exhibited more observer rated negative speech characteristics in an Other-Evaluation condition compared to a Self-Evaluation condition, but high IA individuals and nonanxious individuals did not. These results provide some evidence for the distinctiveness of these dimensions of social anxiety. PMID- 22303844 TI - Nucleic-acid based gene therapeutics: delivery challenges and modular design of nonviral gene carriers and expression cassettes to overcome intracellular barriers for sustained targeted expression. AB - The delivery of nucleic acid molecules into cells to alter physiological functions at the genetic level is a powerful approach to treat a wide range of inherited and acquired disorders. Biocompatible materials such as cationic polymers, lipids, and peptides are being explored as safer alternatives to viral gene carriers. However, the comparatively low efficiency of nonviral carriers currently hampers their translation into clinical settings. Controlling the size and stability of carrier/nucleic acid complexes is one of the primary hurdles as the physicochemical properties of the complexes can define the uptake pathways, which dictate intracellular routing, endosomal processing, and nucleocytoplasmic transport. In addition to nuclear import, subnuclear trafficking, posttranscriptional events, and immune responses can further limit transfection efficiency. Chemical moieties, reactive linkers or signal peptide have been conjugated to carriers to prevent aggregation, induce membrane destabilization and localize to subcellular compartments. Genetic elements can be inserted into the expression cassette to facilitate nuclear targeting, delimit expression to targeted tissue, and modulate transgene expression. The modular option afforded by both gene carriers and expression cassettes provides a two-tier multicomponent delivery system that can be optimized for targeted gene delivery in a variety of settings. PMID- 22303845 TI - Innate predator recognition in giant pandas. AB - Innate predator recognition confers a survival advantage to prey animals. We investigate whether giant pandas exhibit innate predator recognition. We analyzed behavioral responses of 56 naive adult captive giant pandas (Ailuropoda melanoleuca), to urine from predators and non-predators and water control. Giant pandas performed more chemosensory investigation and displayed flehmen behaviors more frequently in response to predator urine compared to both non-predator urine and water control. Subjects also displayed certain defensive behaviors, as indicated by vigilance, and in certain cases, fleeing behaviors. Our results suggest that there is an innate component to predator recognition in captive giant pandas, although such recognition was only slight to moderate. These results have implications that may be applicable to the conservation and reintroduction of this endangered species. PMID- 22303846 TI - Historical effects on local variation in walnut-feeding behavior by the Japanese wood mouse, Apodemus speciosus. AB - The Japanese wood mouse Apodemus speciosus eats large, hard-walled walnuts of Juglans ailanthifolia immediately after finding or after hoarding them. However, not all individuals can efficiently eat the nuts. In this study, to examine local variation in the ability to eat walnuts, feeding behavior was compared among nine wood mouse populations, four from mainland Honshu, where the walnut tree is distributed, and five from the Izu Islands (30-100 km south of Honshu), which lack the tree species. To avoid the effects of pre-capture experience with walnuts, mice from areas lacking the walnut trees were used for testing, even in the Honshu sites. Most mice from Honshu were able to eat walnuts after a 14-day training period, whereas most insular mice could not, with the exception of mice on Kouzushima Island. An analysis of the population genetic structures of these mice based on sequences of the mitochondrial control (D-loop) region revealed that the four insular populations are genetically distinct from the mainland populations, whereas the Kouzushima population remains genetically similar to the mainland populations. The relatively recent colonization of Kouzushima may explain why mice from this island were able to feed on walnuts despite the lack of walnut trees on the island. Thus, walnut-feeding ability appears to have some innate basis in the Japanese wood mouse, and this trait would be selected for in a walnut-available environment as it would better enable mice to survive during food shortages. PMID- 22303847 TI - Binding properties of thyroxine to nuclear extract from sea urchin larvae. AB - We previously reported that thyroid hormones are involved in the formation of the adult rudiment and adult-type skeleton in sea urchin larvae, as well as in the resorption of larval tissues. In the present study, to search for the presence of thyroid hormone receptor in sea urchin larvae, we performed a ligand-binding assay between radiolabeled thyroid hormones and nuclear extracts from the larvae of the sea urchin Hemicentrotus pulcherrimus. The presence of binding sites with a high affinity to thyroxine (T4) was detected in the nuclear extract, but not in the cytoplasmic fraction. The dissociation constants for the T4 binding to the nuclear extracts were estimated to be about 18 pM from the mesenchyme-blastula stage to the four-armed pluteus stage. The quantity of T4 binding sites in the nuclear extracts increased during larval development. These results suggest that the binding affinity to T4 in the nuclear extracts was caused by a putative nuclear thyroid hormone receptor in sea urchin larvae. PMID- 22303848 TI - Expression of beta-adrenergic-like octopamine receptors during Drosophila development. AB - An invertebrate biogenic amine, octopamine, plays diverse roles in multiple physiological processes (e.g. neurotransmitter, neuromodulator, and circulating neurohormone). Octopamine is thought to function by binding to G-protein-coupled receptors. In Drosophila, three beta-adrenergic-like octopamine receptors (Octbeta1R, Octbeta2R, and Octbeta3R) have been identified. We investigated the expression of three OctbetaR genes in embryos, larvae, and adults. These OctbetaRs showed distinct expression patterns in the central nervous system (CNS) throughout development, and Octbeta3R expression was evident in an endocrine organ, the ring gland, in larvae. In larvae, Octbeta1R, Octbeta2R, and Octbeta3R were expressed in salivary glands and imaginal discs, Octbeta2R and Octbeta3R in midgut, and Octbeta3R in gonads. In adult, besides in the CNS, each OctbetaR was strongly expressed in ovary and testis. Our findings provide a basis for understanding the mechanisms by which OctbetaRs mediate multiple diverse octopaminergic functions during development. PMID- 22303849 TI - Complete mitochondrial genome of Locusta migratoria migratoria (Orthoptera: Oedipodidae): three tRNA-like sequences on the N-strand. AB - The complete 16053 bp mitochondrial genome (mitogenome) sequence of Locusta migratoria migratoria has been determined. This mitogenome contains the base compositional biases and codon usage typical of metazoans, and the RSCU values indicate a negative correlation with the C and G contents in codon. The orientation and gene order of the L. migratoria migratoria is identical to Locusta migratoria migratoiodes. An unusual feature of the L. migratoria migratoria mitogenome is the presence of three tRNA-like structures on the N strand: one tRNA(Ile)-like and two tRNA(Leu(CUN))-like sequences. The tRNA-like sequences have proper folding structures and anticodons sequences. Two repeated DNA sequences, Rpt I and Rpt II, were found in the A+T-rich region of the L. migratoria migratoria mitogenome. Both repeated sequences have various features. In the 5' region of Rpt I, a 51 bp fragment is localized in the srRNA gene; and there are two tandemly sub-repeated DNA sequences (sub-Rpts), Rpt 1-4, within Rpt I and Rpt II. One stem-loop structure on the N-strand that may be involved in the N-strand replication initiation was found in the A+T-rich region. PMID- 22303850 TI - The postbranchial digestive tract of the ascidian, Polyandrocarpa misakiensis (Tunicata: Ascidiacea). 2. Stomach. AB - The organization of the stomach in the compound styelid ascidian, Polyandrocarpa misakiensis, is described, and the morphology and cell types of the stomach is discussed from the phylogenetic viewpoint. The stomach is a sac-like organ whose wall is formed into longitudinal folds. The stomach consists of external and internal epithelium. The internal epithelium is simple columnar, except for the bottom of the folds. There are five cell types: absorptive cells, zymogenic cells, endocrine cells, ciliated mucous cells, and undifferentiated cells. The absorptive cells have numerous microvilli. The apical region of these cells is occupied by coated vesicles. The zymogenic cells have a conical outline and a few microvilli on their apical surfaces. There are secretory granules in the apical region of zymogenic cells. The endocrine cells have low cell height and electron dense granules around the nucleus. Endocrine cells have one or two cilia and a few microvilli on the apical surfaces. The basolateral part of these cells often bulges into the adjoining cells. Immunoelectron microscopy revealed that some endocrine cells have serotonin-like immunoreactivity. The ciliated mucous cells are restricted to a single ventral groove. They have numerous microvilli and a few cilia on their apical surfaces. Moderately electron-dense granules are accumulated in the apical part of the ciliated mucous cells. Undifferentiated cells, filled with free ribosomes, form a pseudostratified epithelium in the base of each fold. The nucleus of undifferentiated cells has a prominent nucleolus. The pseudostratified epithelium of the pyloric caecum consists of electron-dense and electron-light cells. PMID- 22303851 TI - Spatial framework of nine distinct local populations of the Japanese dormouse Glirulus japonicus based on matrilineal cytochrome b and patrilineal SRY gene sequences. AB - We previously revealed the presence of six genetically distinct matrilineal populations of the Japanese dormouse Glirulus japonicus in the distribution range of Honshu, Shikoku, and Kyushu islands. In this study, we extended this analysis using mitochondrial cytochrome b gene sequences (n = 96) and Y-chromosome specific SRY gene sequences (n = 22) from individuals collected from Honshu, Shikoku, Kyushu, and Oki Dogo I. The cytochrome b sequence data allowed us to define precise geographic ranges of the six previously known and three newly found distinct matrilineal lineages: northeastern Honshu (I), east-central Honshu (II), west-central Honshu and the Kii Peninsula (III), the western part of Honshu (IV), Shikoku (V), westernmost Honshu and Kyushu (VI), the northern part of central Honshu (VII), the southern part of central Honshu (VIII), and Oki Dogo I. (IX). Our inference of geographic borders suggests that regions of lower and higher altitudes in the mountain systems played important roles in driving the hosting and separation of lineages, respectively. Six matrilineal lineages (I, II, V, VI, VIII, and XI) were shown to possess their own SRY haplotypes, while lineages III and IV shared one haplotype. These data together with our previous observation of nuclear ribosomal RNA gene variation indicate advanced populational subdivision in this species. It is thus evident that each of the populations, including those living at high latitudes and in limited geographic spaces, have survived for several million years. A specific ability to tolerate cold may have permitted G. japonicus to preserve anciently diverged lineages in each locality. PMID- 22303852 TI - Histological observation of the urogenital papillae in the bi-directional sex changing gobiid fish, Trimma okinawae. AB - The gobiid fish Trimma okinawae changes its sex bi-directionally according to its social status. Morphological changes in the urinogenital papillae (UGP) of this fish have been reported during sex change. However, there have been no detailed observations of such changes. Here, we histologically examined the UGP structure of male- and female-phase fish. UGPs of fish in female and male phase contained both oviducts and sperm ducts. Both ducts were coalesced into one duct within the posterior region of the UGP. Female-phase fish had many longitudinal folds in the hypertrophied tunica mucosa of the oviduct, which was found to be responsible for the transport of eggs and the removal of follicular cells from the oocyte. In contrast, male-phase fish had an immature oviduct and a mature sperm duct in the UGP. In the male-phase fish, the co-existence of spermatozoa and fibrillar secretions was observed in the sperm duct during spermiation. PMID- 22303853 TI - A new species of Paramacrochiron (Copepoda: Cyclopoida: Macrochironidae) associated with the rhizostome medusa Rhopilema hispidum collected from the Gulf of Thailand, with a phylogenetic analysis of the family Macrochironidae. AB - Paramacrochiron thailandicum n. sp. (Copepoda: Cyclopoida: Macrochironidae) is described from the rhizostome medusa Rhopilema hispidum occurring in the Gulf of Thailand. The new species is distinguishable from other congeners mainly by detailed features of the fourth legs and the urosome in both sexes. Copepodid and adult stages of the genus Paramacrochiron seem to be host-specific to rhizostome medusae, but may spend periods free in the plankton or benthos during the absence of the host. A cladistic analysis shows that the Macrochironidae comprises two main lineages. Paramacrochiron is recovered as a monophyletic group, located on one lineage together with Pseudomacrochiron, which appears as a paraphyletic taxon with the limited character set used. The other main lineage comprises the genera Macrochiron and Sewellochiron, but the sole species of the latter genus, Sewellochiron fidens, is nested within Macrochiron. This analysis provides little support for maintaining Sewellochiron as a separate genus. PMID- 22303854 TI - Evidence of genetic and reproductive isolation between two morphs of subtropical dominant coral Acropora solitaryensis in the non-reef region of Japan. AB - We reveal the existence of a cryptic species of Acropora solitaryensis ( Veron and Wallace, 1984 ), a dominant species in high-latitude coral communities. Although some morphs, such as arborescent table (AR), solid plate (PL), and intermediate (IM) forms, had been known in this species, it was unclear whether these are reproductively isolated from one another. Here, potential reproductive exchange between two representative morphs, AR and PL, were examined using genetic and reproductive methods. Molecular phylogenetic analyses using both mitochondrial and nuclear molecular markers (mitochondrial control region and mini-collagen intron, respectively) indicated that AR is clearly distinct from PL, suggesting that gene flow between the morphs is absent. In cross fertilization experiments, gametic compatibility between AR and PL was extremely low, suggesting prezygotic isolation of these morphs. These results strongly suggest that AR and IM forms are variations of A. solitaryensis, whereas PL form may be an undescribed species. In addition, AR was closely related genetically to A. pruinosa, which is a high-latitude species with arborescent form, and AR and A. pruinosa were able to hybridize, although with lower fertilities than observed in intra-specific crosses. The two species are thus likely to have speciated not in tropical regions, but in non-reef regions due to habitat segregation. PMID- 22303857 TI - Abnormal glucose regulation and gender-specific risk of fatal coronary artery disease in the HUNT 1 study. AB - OBJECTIVES: To assess fatal coronary artery disease (CAD) by gender and glucose regulation status. DESIGN: 47,951 people were followed up according to fatal CAD identified in the National Cause of Death Registry. Gender-effects of fatal CAD in people with impaired glucose regulation (IGR), newly diagnosed diabetes (NDM) or known diabetes (KDM) compared with people with normal glucose regulation (NGR) were calculated using Cox regression. RESULTS: Using NGR as reference, the hazard ratios (HR, 95% confidence intervals) associated with IGR was 1.2 (0.8-1.9) for women and 1.2 (0.9-1.6) for men. The corresponding HRs were 1.6 (1.2-2.2) and 1.4 (1.1.-1.9) for NDM, and 2.5 (2.1-2.8) and 1.8 (1.6-2.1) for KDM. The gender difference in mortality varied by category (P(interaction) = 0.003). Using women as the reference, the HRs for men were 2.1 (2.0-2.3) for NGR, 1.8 (1.0-3.3) for IGR, 1.6 (1.0-2.5) for NDM, and 1.2 (1.0-1.5) for KDM. CONCLUSIONS: Diabetes mellitus, but not IGR, was associated with fatal CAD in both genders. The known gender-difference in CAD mortality was attenuated in people with abnormal glucose regulation, evident already in people with IGR. PMID- 22303858 TI - Selective atrial vagal denervation guided by evoked vagal reflex to treat refractory vasovagal syncope. AB - A 57-year-old woman with refractory vasovagal syncope and a sinus pause of 6.8 seconds during tilt-table test accepted the suggestion of atrial vagal denervation. Radiofrequency pulses were delivered on positive vagal reflex sites according to the standard of heart rate (HR) drop >=20% after high frequency stimulation (HFS). The endpoint of inexistence of HR decrease at repeating HFS was achieved in 18 sites. No syncope attacked during 12 months and three tilt table tests performed at 1, 6, and 12 months were negative. Extensive ablation on atrial endocardium for vagal denervation is suggested to be efficient in cardioinhibition type of VVS. PMID- 22303859 TI - Chiral cyanide-bridged Cr(III)-Mn(III) heterobimetallic chains based on [(Tp)Cr(CN)3]-: synthesis, structures, and magnetic properties. AB - By the reactions of Mn(III) Schiff-base complexes with the tricyanometalate building block, [(Tp)Cr(CN)(3)](-) (Tp = Tris(pyrazolyl) hydroborate), two couples of enantiomerically pure chiral cyano-bridged heterobimetallic one dimensional (1D) chain complexes, [Mn((R,R) Salcy)Cr(Tp)(CN)(3).1/4H(2)O.1/2CH(2)Cl(2)](n) (1) and [Mn((S,S) Salcy)Cr(Tp)(CN)(3).1/4H(2)O.1/2CH(2)Cl(2)](n) (2) (Salcy = N,N'-(1,2 cyclohexanediylethylene)bis(salicylideneiminato) dianion), [Mn((R,R) Salphen)Cr(Tp)(CN)(3)](n) (3) and [Mn((S,S)-Salphen)Cr(Tp)(CN)(3)](n) (4) (Salphen = N,N'-1,2-diphenylethylene-bis(salicylideneiminato) dianion), have been successfully synthesized. Circular dichroism (CD) spectra confirm the enantiomeric nature of the optically active complexes. Structural analyses reveal the formation of neutral cyano-bridged zigzag single chains in 1 and 2, and neutral cyano-bridged zigzag double chains in 3 and 4. Magnetic studies show that antiferromagnetic couplings are operative between Cr(III) and Mn(III) centers bridged by cyanide. Complexes 1 and 2 are the rare examples of chiral ferrimagnets; while complexes 3 and 4 exhibit a coexistence of chirality and spin glass behavior in a 1D chain. PMID- 22303860 TI - Current SEM techniques for de- and re-construction of centromeres to determine 3D CENH3 distribution in barley mitotic chromosomes. AB - Combined light microscopic (LM) and field emission scanning electron microscopic (FESEM) techniques with FluoroNanogold labelling allowed quantification and high resolution analysis of 3D distribution of the centromere-specific histone H3 variant CENH3 in barley mitotic chromosomes. Chromosomes were investigated with fluorescence LM, conventional FESEM, low-voltage FESEM and combined FIB/FESEM techniques for unprecedented comprehensive analysis to determine chromatin distribution patterns in the centromere. Using data from FIB/FESEM sectioning of centromeric regions of chromosomes, it was possible to render 3D reconstruction of the CENH3 distribution with highest resolution achieved to date. Complementary data derived from each approach show that CENH3 localizes not only to the primary constriction, but also in the pericentric regions and is distributed exclusively in the interior, rather than on the surface, of the centromere. This is relevant for understanding kinetochore assembly and digresses from current models of centromere structure. We emphasize here this broad microscopic approach, focusing on technical aspects of combined FESEM techniques, for which advantages and limitations are discussed, providing a relevant example--in the field of centromeric research--for application to investigations of other subcellular biological structures. PMID- 22303863 TI - Effect of intraarterial papaverine or nimodipine on vessel diameter in patients with cerebral vasospasm after subarachnoid hemorrhage. AB - INTRODUCTION: Papaverine (P) and nimodipine (N) are the most widely used vasodilators when angiographic and symptomatic vasospasm is present after subarachnoid aneurysmatic hemorrhage (SAH). Their effect is only short-lived and no direct comparisons have been undertaken to evaluate the action of both substances directly. We retrospectively assessed the effect of either P or N on angiographic diameter reduction and capillary blood flow. METHODS: Fifteen SAH patients with secured aneurysms and cerebral vasospasm received intraarterial P, fifteen similar patients received N. As the primary endpoint, pre- and post infusion arterial diameters and capillary blood flow were rated retrospectively on angiographies and compared by RM-ANOVA. Secondary endpoints were the difference in the modified Rankin Scale between the two groups on admission and at discharge, the occurrence of delayed cerebral ischemia, the separate effects on angiographic diameter and capillary blood flow and the overall response rate to the vasodilator infusion. RESULTS: Angiographic resolution of diameter reduction and angiographically assessed capillary blood flow together differed not significantly between both groups. P infusion dilated all angiographic demonstrable vessels while N infusion was ineffective in 16% of the patients. Capillary flow on pre- and post-infusion angiographies was not different between the two groups. CONCLUSION: P and N seem to differ in the effect on cerebral diameter reduction in patients with vasospasm after SAH. The clinical implications remain to be established. A multimodal approach, perhaps combining different agents for intraarterial infusion in such patients, needs to be evaluated. PMID- 22303861 TI - Delivery method, target gene structure, and growth properties of target cells impact mutagenic responses to reactive nitrogen and oxygen species. AB - Dysregulated production of nitric oxide (NO*) and reactive oxygen species (ROS) by inflammatory cells in vivo may contribute to mutagenesis and carcinogenesis. Here, we compare cytotoxicity and mutagenicity induced by NO* and ROS in TK6 and AS52 cells, delivered by two methods: a well-characterized delivery system and a novel adaptation of a system for coculture. When exposed to preformed NO*, a cumulative dose of 620 MUM min reduced the viability of TK6 cells at 24 h to 36% and increased mutation frequencies in the HPRT and TK1 genes to 7.7 * 10-6 (p < 0.05) and 24.8 * 10-6 (p < 0.01), 2.7- and 3.7-fold higher than background, respectively. In AS52 cells, cumulative doses of 1700 and 3700 MUM min reduced viability to 49 and 22%, respectively, and increased the mutation frequency 10.2- and 14.6-fold higher than the argon control (132 * 10-6 and 190 * 10-6, respectively). These data show that TK6 cells were more sensitive than AS52 cells to killing by NO*. However, the two cell lines were very similar in relative susceptibility to mutagenesis; on the basis of fold increases in MF, average relative sensitivity values [(MF(exp)/MF(control))/cumulative NO* dose] were 5.16 * 10-3 and 4.97 * 10-3 MUM-1 min-1 for TK6 cells and AS52 cells, respectively. When AS52 cells were exposed to reactive species generated by activated macrophages in the coculture system, cell killing was greatly reduced by the addition of NMA to the culture medium and was completely abrogated by combined additions of NMA and the superoxide scavenger Tiron, indicating the relative importance of NO* to loss of viability. Exposure in the coculture system for 48 h increased mutation frequency in the gpt gene by more than 9-fold, and NMA plus Tiron again completely prevented the response. Molecular analysis of gpt mutants induced by preformed NO* or by activated macrophages revealed that both doubled the frequency of gene inactivation (40% in induced vs 20% in spontaneous mutants). Sequencing showed that base-substitution mutations dominated the spectra, with transversions (30-40%) outnumbering transitions (10-20%). Virtually all mutations took place at guanine sites in the gene. G:C to T:A transversions accounted for about 30% of both spontaneous and induced mutations; G:C to A:T transitions amounted to 10-20% of mutants; insertions, small deletions, and multiple mutations were present at frequencies of 0-10%. Taken together, these results indicate that cell type and proximity to generator cells are critical determinants of cytotoxic and genotoxic responses induced by NO* and reactive species produced by activated macrophages. PMID- 22303864 TI - Ventriculoperitoneal shunt-related infections caused by Staphylococcus epidermidis: pathogenesis and implications for treatment. AB - The insertion of medical devices, such as intraventricular shunts, is often complicated by infection leading to ventriculitis. Frequently, such infections result from colonisation and subsequent biofilm formation on the surfaces of the shunts by Staphylococcus epidermidis. The pathogenesis of neurosurgical shunt related infection is complex with interactions between the pathogen, the device and the unique local immunological environment of the central nervous system (CNS). An ability to form biofilm, the main virulence determinant of Staphylococcus epidermidis, facilitates protection of the organism from the host defences while still initiating an immunological response. The presence of the blood brain barrier (BBB) and the biofilm itself also complicates treatment, which presents many challenges when managing shunt infections. A greater understanding of the interplay between S. epidermidis and the CNS could potentially improve the diagnosis, treatment and management of such infections. This review describes the pathogenesis, treatment and implications of S. epidermidis ventriculoperitoneal shunt-related infections, concentrating on recent research and the implications for treatment. PMID- 22303865 TI - Excited-state dynamics and self-organization of poly(3-hexylthiophene) (P3HT) in solution and thin films. AB - The fluorescence decays of a stereoregular head-to-tail RR-HT poly(3 hexylthiophene), P3HT, in methylcyclohexane (MCH) are described by sums of three or four exponential terms, respectively above and below -10 degrees C. In the high-temperature region, the polymer lifetime (ca. 500 ps) is accompanied by two shorter decay times (ca. 20 and 120 ps), which are assigned to intrachain energy transfer from high to lower energy excitons on the basis of temperature and wavelength dependence of the fluorescence decays. The absence of conformational (torsional) relaxation is attributed to the small dihedral angle between monomers that is predicted for the stereoregular polymer in the ground state. Below -10 degrees C, the polymer forms excimer-like aggregates, showing vibrational structured absorption and emission bands similar to those observed in thin films. The vibrational structure is attributed to a deep minimum in the ground-state energy surface of the dimer or aggregate. Below -40 degrees C, the fluorescence measured at the aggregate emission wavelength (670 nm) basically results from direct excitation of the aggregate and decays with a sum of three exponential terms (decay times of ca. 0.14, 0.6, and 1.5 ns, with similar weights). Because the spectral similarities between film and aggregates indicate similar electronic first singlet excited states (and oscillator strengths), the much shorter decay times (0.05, 0.15, and 0.43 ns) and lower fluorescence quantum yield of P3HT in films are assigned to efficient exciton dissociation and/or phonon-induced internal conversion competing with radiative decay (>1 ns). PMID- 22303866 TI - Macroscopic multifunctional graphene-based hydrogels and aerogels by a metal ion induced self-assembly process. AB - We report a one-step fabrication of macroscopic multifunctional graphene-based hydrogels with robust interconnected networks under the synergistic effects of the reduction of graphene oxide sheets by ferrous ions and in situ simultaneous deposition of nanoparticles on graphene sheets. The functional components, such as alpha-FeOOH nanorods and magnetic Fe(3)O(4) nanoparticles, can be easily incorporated with graphene sheets to assemble macroscopic graphene monoliths just by control of pH value under mild conditions. Such functional graphene-based hydrogels exhibit excellent capability for removal of pollutants and, thus, could be used as promising adsorbents for water purification. The method presented here is proved to be versatile to induce macroscopic assembly of reduced graphene sheets with other functional metal oxides and thus to access a variety of graphene-based multifunctional nanocomposites in the form of macroscopic hydrogels or aerogels. PMID- 22303867 TI - Photoinduced electron transfer across a molecular wall: coumarin dyes as donors and methyl viologen and TiO2 as acceptors. AB - Coumarins C-153, C-480, and C-1 formed 1:2 (guest:host) complexes with a water soluble cavitand having eight carboxylic acid groups (OA) in aqueous borate buffer solution. The complexes were photoexcited in the presence of electron acceptors (methyl viologen, MV(2+), or TiO(2)) to probe the possibility of electron transfer between a donor and an acceptor physically separated by a molecular wall. In solution at basic pH, the dication MV(2+) was associated to the exterior of the complex C-153@OA(2), as suggested by diffusion constants (~1.2 * 10(-6) cm(2)/s) determined by DOSY NMR. The fluorescence of C-153@OA(2) was quenched in the presence of increasing amounts of MV(2+) and Stern-Volmer plots of I(o)/I and tau(o)/tau vs [MV(2+)] indicated that the quenching was static. As per FT-IR-ATR spectra, the capsule C-153@OA(2) was bound to TiO(2) nanoparticle films. Selective excitation (lambda(exc) = 420) of the above bound complex resulted in fluorescence quenching. When adsorbed on insulating ZrO(2) nanoparticle films, excitation of the complex resulted in a broad fluorescence spectrum centered at 500 nm and consistent with C-153 being within the lipophilic capsule interior. Consistent with the above results, colloidal TiO(2) quenched the emission while colloidal ZrO(2) did not. PMID- 22303868 TI - A prelinguistic gestural universal of human communication. AB - Several cognitive accounts of human communication argue for a language independent, prelinguistic basis of human communication and language. The current study provides evidence for the universality of a prelinguistic gestural basis for human communication. We used a standardized, semi-natural elicitation procedure in seven very different cultures around the world to test for the existence of preverbal pointing in infants and their caregivers. Results were that by 10-14 months of age, infants and their caregivers pointed in all cultures in the same basic situation with similar frequencies and the same proto-typical morphology of the extended index finger. Infants' pointing was best predicted by age and caregiver pointing, but not by cultural group. Further analyses revealed a strong relation between the temporal unfolding of caregivers' and infants' pointing events, uncovering a structure of early prelinguistic gestural conversation. Findings support the existence of a gestural, language-independent universal of human communication that forms a culturally shared, prelinguistic basis for diversified linguistic communication. PMID- 22303869 TI - A domino approach of Heck coupling for the synthesis of beta trifluoromethylstyrenes. AB - A domino approach of Heck coupling was used to synthesize beta trifluoromethylstyrene derivatives from iodoarenes and 1-iodo-3,3,3 trifluoropropane in moderate to good yields. This method avoids the use of low boiling, gaseous reagents such as 3,3,3-trifluoropropene, and additives and phosphines in the catalytic system. PMID- 22303870 TI - Characteristic features of stem cells in glioblastomas: from cellular biology to genetics. AB - Glioblastoma is the most common type of primary brain tumor in adults and is among the most lethal and least successfully treated solid tumors. Recently, research into the area of stem cells in brain tumors has gained momentum. However, due to the relatively new and novel hypothesis that a subpopulation of cancer cells in each malignancy has the potential for tumor initiation and repopulation, the data in this area of research are still in its infancy. This review article is aimed at attempting to bring together research carried out so far in order to build an understanding of glioblastoma stem cells (GSCs). Initially, we consider GSCs at a morphological and cellular level, and then discuss important cell markers, signaling pathways and genetics. Furthermore, we highlight the difficulties associated with what some of the evidence indicates and what collectively the studies contribute to further defining the interpretation of GSCs. PMID- 22303871 TI - Unique structural features of interconverting monomeric and dimeric G quadruplexes adopted by a sequence from the intron of the N-myc gene. AB - A multidimensional heteronuclear NMR study has demonstrated that a guanine-rich DNA oligonucleotide originating from the N-myc gene folds into G-quadruplex structures in the presence of K(+), NH(4)(+), and Na(+) ions. A monomeric G quadruplex formed in K(+) ion containing solution exhibits three G-quartets and flexible propeller-type loops. The 3D structure with three single nucleotide loops represents a missing element in structures of parallel G-quadruplexes. The structural features together with the high temperature stability are suggestive of the specific biological role of G-quadruplex formation within the intron of the N-myc gene. An increase in K(+) ion and oligonucleotide concentrations resulted in transformation of the monomeric G-quadruplex into a dimeric form. The dimeric G-quadruplex exhibits six stacked G-quartets, parallel strand orientations, and propeller-type loops. A link between the third and the fourth G quartets consists of two adenine residues that are flipped out to facilitate consecutive stacking of six G-quartets. PMID- 22303872 TI - Action learning enhances professional development of research supervisors: an Australian health science exemplar. AB - The worldwide academic workforce is ageing. At the same time, health and human services workforces are expanding. The preparation of educators to fill gaps in expertise and to position the health sciences for future growth is an urgent need. The findings from a recent action learning project that aimed to enhance the professional growth and development of higher degree researcher student supervisors in a School of Health and Human Sciences are presented. Seven early career researchers and the facilitator met for two hours every two to three weeks over 4 months between April and July 2010, in a rural and regional university in New South Wales, Australia. The processes initiated were a combination of experiential knowledge, referral to relevant published reports, use of an effective supervision checklist, and critical conversations. Learning outcomes centered on higher degree management and supervision pedagogy, communities of practice, knowledge translation, and the establishment of a research culture. The contextual barriers and implications of the methodology and learning outcomes for the professional development of health and human science practitioners, researchers and educators is also discussed. PMID- 22303873 TI - Electrophysiological evaluation of sensory and motor pathways after incomplete unilateral spinal cord contusion. AB - OBJECT: Unilateral contusions represent an increasingly popular model for studying the pathways and recovery mechanisms of spinal cord injury (SCI). Current studies rely heavily on motor behavior scoring and histological evidence to make assessments. Electrophysiology represents one way to reliably quantify the functionality of motor pathways. The authors sought to quantify the functional integrity of the bilateral motor and sensory pathways following unilateral SCI by using measurements of motor and somatosensory evoked potentials (MEPs and SSEPs, respectively). METHODS: Eighteen rats were randomly divided into 3 groups receiving a mild unilateral contusion, a mild midline contusion, or a laminectomy only (control). Contusions were induced at T-8 using a MASCIS impactor. Electrophysiological analysis, motor behavior scoring, and histological quantifications were then performed to identify relationships among pathway conductivity, motor function, and tissue preservation. RESULTS: Hindlimb MEPs ipsilateral to the injury showed recovery by Day 28 after injury and corresponded to approximately 61% of spared corticospinal tract (CST) tissue. In contrast, MEPs of the midline-injured group did not recover, and correspondingly > 90% of the CST tissue was damaged. Somatosensory evoked potentials showed only a moderate reduction in amplitude, with no difference in latency for the pathways ipsilateral to injury. Furthermore, these SSEPs were significantly better than those of the midline-injured rats for the same amount of white matter damage. CONCLUSIONS: Motor evoked potential recovery corresponded to the amount of spared CST in unilateral and midline injuries, but motor behavior consistently recovered independent of MEPs. These data support the idea that spared contralateral pathways aid in reducing the functional deficits of injured ipsilateral pathways and further support the idea of CNS plasticity. PMID- 22303874 TI - A qualitative description of the peptide sharing between poliovirus and Homo sapiens. AB - In a companion paper, we reported that pentapeptides from human poliovirus 1, Mahoney strain, occur repeatedly in human proteins for a total of more than 18,000 overlaps. In the present study, we describe the distribution of the polio pentapeptides throughout biochemical pathways and networks characterizing functions and tissues in the human host. The present study might be of help to better define the poliovirus-host relationships as well as for designing peptide modules with anti-polio activity. PMID- 22303875 TI - Use of propranolol for infantile hemangiomas. AB - Treating infantile hemangiomas may be associated with significant morbidity. Recently, propranolol, a nonselective beta-blocker, has become a reputed and successful treatment modality for infantile hemangiomas. Here, the author presents experience with oral propranolol in treatment of 14 patients with infantile hemangiomas. The drug was tolerated well and no side effects except reversible bronchospasm in 3 were observed during treatment. Eleven of the patients, younger than 1 year, showed a good response, with more than 50% reduction in the size of the hemangiomas. Although there are a limited number of patients, these results showed that oral propranolol therapy is a safe and effective choice in the treatment of infantile hemangiomas before the age of 1 year. PMID- 22303876 TI - The hydrogen bond environments of 1H-tetrazole and tetrazolate rings: the structural basis for tetrazole-carboxylic acid bioisosterism. AB - Bioisosterism involving replacement of a carboxylic acid substituent by 1H tetrazole, yielding deprotonated carboxylate and tetrazolate under physiological conditions, is a well-known synthetic strategy in medicinal chemistry. To improve our overall understanding of bioisosterism, we have used this example to study the geometrical and energetic aspects of the functional group replacement. Specifically, we use crystal structure informatics and high-level ab initio calculations to study the hydrogen bond (H-bond) energy landscapes of the protonated and deprotonated bioisosteric pairs. Each pair exhibits very similar H bond environments in crystal structures retrieved from the CSD, and the attractive energies of these H-bonds are also very similar. However, by comparison with -COOH and -COO(-), the H-bond environments around 1H-tetrazole and tetrazolate substituents extend further, by about 1.2 A, from the core of the connected molecule. Analysis of pairs of PDB structures containing ligands which differ only in having a tetrazole or a carboxyl substituent and which are bound to the same protein indicates that the protein binding site must flex sufficiently to form strong H-bonds to either substituent. A survey of DrugBank shows a rather small number of tetrazole-containing drugs in the 'approved' and 'experimental' drug sections of that database. PMID- 22303877 TI - Mechanisms of neutrophil-mediated disease: innovative therapeutic interventions. AB - Over recent years, neutrophil functions have extensively been reevaluted. For instance, it has been found that extracellular traps generated by activated neutrophils are able to perform a very effective antimicrobial activity against a plethora of microorganisms. In addition, neutrophils possess the ability to interact with monocytes/macrophages either via release of their granule content or via efferocytosis. Efferocytosis is based on neutrophil clearance by macrophages, which, in turn, exert pro- or antinflammatory effects. Furthermore, alarmins released by neutrophils have been shown to mobilize and activate dendritic cells as well as macrophages for antigenpresentation to occur. Finally, other researchers have demonstrated that neutrophils act as suppressor cells by deprivation of arginine in T cells. From a clinical point of view, it is well known that neutrophils are present as activated effector cells in a number of diseases such as infectious disease, sepsis, autoimmune disease, cardiovascular disease and tumors. They play pro-inflammatory and angiogenetic effects in some cases, while in other cases they depress host immune response. In this review, also emphasis will be placed on neutrophil functional deficits which seem to participate to the pathogenesis of various diseases, e.g., viral hepatitis C infection and inflammatory bowel disease. Finally, novel therapeutic measures able to modulate neutrophil functions will be described with special reference to both immune agents and natural products. PMID- 22303878 TI - Hyper-activation of WNT/beta-catenin signaling pathway mediates anti-tumor effects of histone deacetylase inhibitors in acute T lymphoblastic leukemia. AB - Histone deacetylase inhibitors (HDACis) are promising agents for the treatment of acute T lymphoblastic leukemia (T-ALL). However, the underlying mechanisms remain to be elucidated. Based on a recent study showing that HDACis were able to modulate WNT/beta-catenin signaling, we further investigated the influence of HDACis on WNT/beta-catenin signaling in T-ALL cells and modulation of WNT/beta catenin signaling in mediating anti-leukemic effects of HDACis. Results from Western blotting, immunocytochemistry and a luciferase reporter assay consistently suggested that two HDACis, valproic acid (VPA) and suberoyl bishydroxamic acid (SBHA), augmented WNT/beta-catenin signaling in T-ALL cells. Meanwhile, VPA and SBHA dramatically inhibited cell growth, blocked G2/M cell cycle progression and increased p21(WAF1) expression. In addition, the levels of cleaved caspase-9, caspase-3 and poly(ADP-ribose) polymerase (PARP) were elevated, indicating induction of apoptosis. Furthermore, flow cytometry and Western blot for cleaved PARP showed that targeting beta-catenin with shRNA attenuated the apoptosis induced by VPA and SBHA. These data demonstrate that HDACis exert profound anti-leukemic effects partly by augmentation of WNT/beta catenin signaling. Using HDACis to modulate WNT/beta-catenin signaling could be an attractive new strategy for the treatment of T-ALL. PMID- 22303879 TI - Circulating microparticles and endothelial progenitor cells in atherosclerosis: pharmacological effects of irbesartan. AB - AIMS: This study aimed to (i) employ our newly designed model, the hypertensive hypercholesterolemic hamster (HH), in order to find out whether a correlation exists between circulating microparticles (MPs), endothelial progenitor cells (EPCs) and their contribution to vascular dysfunction and (ii) to assess the effect of irbesartan treatment on HH animals (HHI). METHODS AND RESULTS: The results showed that compared with the control (C) group, HH displayed: (i) a significant increase in plasma cholesterol and triglyceride concentration, and an augmentation of systolic and diastolic arterial blood pressure, and of heart rate; (ii) a marked elevation of MPs and a significant decrease in EPCs; (iii) structural modifications of the arterial wall correlated with altered protein expression of MMP2, MMP9, MMP12, TIMP1, TIMP2 and collagen type I and III; (iv) a considerably altered reactivity of the arterial wall closely correlated with MPs and EPC adherence; and (v) an inflammatory process characterized by augmented expression of P-Selectin, E-Selectin, von Willebrand factor, tissue factor, IL-6, MCP-1 and RANTES. Additionally, the experiments showed the potential of irbesartan to correct all altered parameters in HH and to mobilize EPCs by NO, chemokines and adhesion molecule-dependent mechanisms. CONCLUSIONS: Hypertension associated with hypercholesterolemia is accompanied by structural modifications and expression of pro-inflammatory molecules by the vessel wall, the alteration of vascular tone, enhanced release of MPs and reduced EPCs; the ratio between the latter two may be considered as a marker of vascular dysfunction. Irbesartan, which exhibits a pharmacological control on the levels of MPs and EPCs, has the potential to restore homeostasis of the arterial wall. PMID- 22303880 TI - Spontaneous multiscale phase separation within fluorinated xerogel coatings for fouling-release surfaces. AB - Four-component xerogel films consisting of 1 mole-% n-octadecyltrimethoxysilane (C18) and 50 mole-% tetraethoxysilane (TEOS) in combination with 1-24 mole-% tridecafluoro-1,1,2,2-tetrahydrooctyltriethoxysilane (TDF) and 25-48 mole-% n octyltriethoxysilane (C8) and a 1:49:50 mole-% C18/TDF/TEOS were prepared. Settlement of barnacle cyprids and removal of juvenile barnacles, settlement of zoospores of the alga Ulva linza, and strength of attachment of 7-day sporelings (young plants) of Ulva were compared amongst the xerogel formulations. Several of the xerogel formulations were comparable to poly(dimethylsiloxane) elastomer with respect to removal of juvenile barnacles and removal of sporeling biomass. The 1:4:45:50 and 1:14:35:50 C18/TDF/C8/TEOS xerogels displayed some phase segregation by atomic force microscopy (AFM) pre- and post-immersion in water. Imaging reflectance infrared microscopy showed the formation of islands of alkane rich and perfluoroalkane-rich regions in these same xerogels both pre- and post immersion in water. Surface energies were unchanged upon immersion in water for 48 h amongst the TDF-containing xerogel coatings. AFM measurements demonstrated that surface roughness on the 1:4:45:50 and 1:14:35:50 C18/TDF/C8/TEOS xerogel coatings decreased upon immersion in water. PMID- 22303881 TI - Limitations of Chromogranin A in clinical practice. AB - CONTEXT: Usefulness of circulating Chromogranin A (CgA) for the diagnosis of neuroendocrine tumors (NEN) is controversial. The aim of the present study was to assess the actual role of this marker as diagnostic tool. METHODS: Serum blood samples were obtained from 42 subjects affected with NEN, 120 subjects affected with non-endocrine neoplasias (non-NEN) and 100 non-neoplastic subjects affected with benign nodular goitre (NNG). Determination of CgA was performed by means of immunoradiometric assay. RESULTS: The CgA levels among NEN-patients were not significantly different from NNG and non-NEN subjects. The Receiver operating characteristic (ROC) curves analysis failed to identify a feasible cut-off value for the differential diagnosis between NEN and the other conditions. CONCLUSION: Serum CgA is not helpful for the first-line diagnosis of NEN. PMID- 22303882 TI - Significance of missing telemetered markers in implanted cardioverter defibrillators. AB - BACKGROUND: We report three patients with St Jude ICDs (St. Jude Medical, Sylmar, CA, USA) where some aspect of the marker channel was missing. METHODS AND RESULTS: Two cases were caused by the simultaneous occurrence of two distinct cardiac or device events that affected the proper delivery of markers by the telemetry system. Inability of the devices to sequentially process these events resulted in incomplete transmission of telemetry data to the programmers and caused missing markers in the telemetry recordings. In the third case, sensed atrial interference resulted in a short period of atrial asynchronous pacing, which prevented the delivery of a sensed atrial marker coincident with an atrial electrogram. This atrial electrogram by virtue of its timing would have otherwise been sensed outside the atrial refractory period. CONCLUSION: The perplexing recordings of the three patients should not be interpreted as representing true pacemaker malfunction. PMID- 22303883 TI - Aptamer-based viability impedimetric sensor for viruses. AB - The development of aptamer-based viability impedimetric sensor for viruses (AptaVISens-V) is presented. Highly specific DNA aptamers to intact vaccinia virus were selected using cell-SELEX technique and integrated into impedimetric sensors via self-assembly onto a gold microelectrode. Remarkably, this aptasensor is highly selective and can successfully detect viable vaccinia virus particles (down to 60 virions in a microliter) and distinguish them from nonviable viruses in a label-free electrochemical assay format. It also opens a new venue for the development of a variety of viability sensors for detection of many microorganisms and spores. PMID- 22303884 TI - Has folate a role in the developing nervous system after birth and not just during embryogenesis and gestation? AB - It is now 30 years since the first publications stating that supplementation with folate could prevent neural tube defects appeared and 20 years since the definitive data, including prevention of other birth defects. Since then epidemiological studies and animal experiments have identified folate as a molecule at the crossroads of neural development. Fortification of food has greatly reduced the incidence of spina bifida. Much interest has focussed on long term sequelae in children born to mothers severely deprived of folate (and other nutrients) such as during the Dutch Hunger Winter of 1944 and in poor parts of the world. In addition, deficiency in folate and B12 are increasingly discussed as a possible contributing factor in dementia and congenital orofacial and heart malformations. The year 2011 saw the publication of a study that implicated low folate intake in poorer school performance of adolescents as judged by school marks. This has enormous social implications but needs confirmation from other settings. This review assesses the current state of evidence and sets the data in context of whether folate has a role in the development and plasticity of the nervous system even after birth, with particular emphasis on childhood and adolescence. PMID- 22303885 TI - A retrievable and highly selective fluorescent probe for monitoring sulfide and imaging in living cells. AB - A novel selective fluorescent chemosensor based on an 8-hydroxyquinoline-appended fluorescein derivative (L1) was synthesized and characterized. Once combined with Cu(2+), it displayed high specificity for sulfide anion. Among the various anions, only sulfide anion induced the revival of fluoresecence of L1, which was quenched by Cu(2+), resulting in "off-on"-type sensing of sulfide anion. What's more, the sensor was retrievable to indicate sulfide anions with Cu(2+), and S(2 ), in turn, increased. With the addition of Cu(2+), compound L1 could give rise to a visible pink-to-yellow color change and green fluorescence quenching. The resulting yellow solution could change to pink and regenerate to green fluorescence immediately upon the addition of sulfide anion; however, no changes were observed in the presence of other anions, including CN(-), P(2)O(7)(4-), and other forms of sulfate, making compound L1 an extremely selective and efficient sulfide chemosensor. The signal transduction occurs via reversible formation separation of complex L1Cu and CuS. What's more, the biological imaging study has demonstrated that the chemosensor can detect sulfur anions in biological systems at a relatively low concentration. PMID- 22303888 TI - Circadian regulation of the hepatic endobiotic and xenobitoic detoxification pathways: the time matters. AB - Metabolic processes have to be regulated tightly to prevent waste of energy and to ensure sufficient detoxification. Most anabolic processes operate in a timely manner when energy intake is the highest, while catabolism takes place in energy spending periods. Endobiotic and xenobiotic metabolism are therefore under circadian control. Circadian regulation is mediated through the suprachiasmatic nucleus (SCN), a master autonomous oscillator of the brain. Although many peripheral organs have their own oscillators, the SCN is important in orchestrating and entraining organs according to the environmental light cues. However, light is not the only signal for entrainment of internal clocks. For endobiotic and xenobitoic detoxification pathways, the food composition and intake regime are equally important. The rhythm of the liver as an organ where the major metabolic pathways intersect depends on SCN signals, signals from endocrine tissues, and, importantly, the type and time of feeding or xenobiotics ingestion. Several enzymes are involved in detoxification processes. Phase I is composed mainly of cytochromes P450, which are regulated by nuclear receptors. Phase II enzymes modify the phase I metabolites, while phase III includes membrane transporters responsible for the elimination of modified xenobiotics. Phases I-III of drug metabolism are under strong circadian regulation, starting with the drug-sensing nuclear receptors and ending with drug transporters. Disturbed circadian regualtion (jet-lag, shift work, and dysfunction of core clock genes) leads to changed periods of activity, sleep disorders, disturbed glucose homeostasis, breast or colon cancer, and metabolic syndrome. As many xenobiotics influence the circadian rhythm of the liver, bad drug administration timing can worsen the above listed effects. This review will cover the major hepatic circadian regulation of endogenous and xenobiotic metabolic pathways and will provide examples of how good timing of drug administration can change drug failure to treatment success. PMID- 22303887 TI - Ketamine for treatment-resistant unipolar depression: current evidence. AB - Currently available drugs for unipolar major depressive disorder (MDD), which target monoaminergic systems, have a delayed onset of action and significant limitations in efficacy. Antidepressants with primary pharmacological targets outside the monoamine system may offer the potential for more rapid activity with improved therapeutic benefit. The glutamate system has been scrutinized as a target for antidepressant drug discovery. The purpose of this article is to review emerging literature on the potential rapid-onset antidepressant properties of the glutamate NMDA receptor antagonist ketamine, an established anaesthetic agent. The pharmacology of ketamine and its enantiomer S-ketamine is reviewed, followed by examples of its clinical application in chronic, refractory pain conditions, which are commonly co-morbid with depression. The first generation of studies in patients with treatment-resistant depression (TRD) reported the safety and acute efficacy of a single subanaesthetic dose (0.5 mg/kg) of intravenous ketamine. A second generation of ketamine studies is focused on testing alternate routes of drug delivery, identifying methods to prevent relapse following resolution of depressive symptoms and understanding the neural basis for the putative antidepressant actions of ketamine. In addition to traditional depression rating endpoints, ongoing research is examining the impact of ketamine on neurocognition. Although the first clinical report in MDD was published in 2000, there is a paucity of adequately controlled double-blind trials, and limited clinical experience outside of research settings. Given the potential risks of ketamine, safety considerations will ultimately determine whether this old drug is successfully repositioned as a new therapy for TRD. PMID- 22303889 TI - Elderly men with a history of distal radius fracture have significantly lower calcaneal bone density and free androgen index than age-matched controls. AB - BACKGROUND: Age related bone loss is widely accepted as related to decreased serum levels of circulating sex hormones. Epidemiological data also show distal radius fractures in men to be a sensitive marker of bone fragility. The aim of this study was to assess if men with a history of distal radius fracture have lower bone mass density (BMD), lower free androgen index (FAI), lower total testosterone (T) and lower bio-available testosterone (Bio-T) than healthy age matched controls. PATIENTS AND METHODS: A case-control study is based on consecutive cases treated for low energy distal radius fracture at our department and age-matched controls. Thirty-nine men treated between 1997-2004 and 45 age matched controls underwent calcaneal bone density measurements (t-score) and analyses of T, Bio-T and serum hormone binding globulin (SHBG). RESULTS: The fracture group had lower BMD (p < 0.01) and lower FAI (p = 0.01). Linear regression analysis showed a correlation between Bio-T and t-scores (p = 0.03). Using analysis of covariance, a significant difference with lower Bio-T in the fracture group was shown. CONCLUSION: Bio-T seems to correlate with BMD in elderly men and may serve as a marker for increased fracture risk in this patient group. PMID- 22303890 TI - Copper can still be epitaxially deposited on palladium nanocrystals to generate core-shell nanocubes despite their large lattice mismatch. AB - Here we report the synthesis of Pd@Cu core-shell nanocubes via epitaxial growth, where the lattice mismatch is 7.1%. The synthesis involved the use of Pd seeds with different shapes (including cubes, cuboctahedra, and octahedra) for the epitaxial growth of Cu shells. Different from the conventional growth mode, Cu atoms initially nucleated only on a few of the many faces of a Pd seed, onto which more Cu atoms were continuously added to generate Cu blocks. Later, the Cu atoms also started to nucleate and grow on other faces of the Pd seed until the entire surface of the seed was covered by a Cu shell. As a result, the Pd seed was rarely located in the center of each core-shell structure. The final product took a cubic shape enclosed by {100} facets regardless of the type of Pd seeds used because of the selective capping of Cu(100) surface by hexadecylamine. The edge lengths of the Pd@Cu nanocubes could be tuned from 50 to 100 nm by varying the amount of Pd seeds while keeping the amount of CuCl(2) precursor. PMID- 22303892 TI - Difference between magainin-2 and melittin assemblies in phosphatidylcholine bilayers: results from coarse-grained simulations. AB - We performed coarse-grained computer simulations using MARTINI force field to study the difference in the self-assembly and possible pore creation in DPPC phospholipid membranes by two different antimicrobial peptides: magainin-2 and melittin. Simulations showed that magainin-2 peptides create large sized disordered toroidal pores that allow easy water permeation across them. Melittin assemblies contain peptides in U-shaped conformations that, although creating holes in membranes, block effectively the passage of water. These observed structures are consistent with the dye efflux experiments performed on vesicles exposed to solutions containing antimicrobial peptides. PMID- 22303893 TI - Analysis of Giardia lamblia interactions with polymer surfaces using a microarray approach. AB - The interaction of the waterborne protozoan parasite, Giardia lamblia, with polymeric materials was investigated by microarray screening of 652 polymers. Polymers were identified which either bound G. lamblia cysts or prevented their binding. Correlation of material properties such as wettability and surface roughness with cyst attachment revealed no influence of these factors upon Giardia adhesion. However, the study of polymer composition allowed the correlation of binding and generation of polymer structure function relationships; glycol and aromatic functionalities appeared to prevent adhesion, whereas secondary amine groups promoted adhesion, in agreement with previous literature. A significant reduction in attachment was observed following both cyst treatments with proteinase K and performing experiments at extremes of pH (2 and 12). It is suggested that proteinase K removes the proteins needed for specific surface interactions, whereas extremes of pH influence either protonation of the polymer or the surface charge of the cysts. The mechanism by which the protozoa attach to polymeric surfaces is proposed to be through ion pair interactions. Improved understanding of G. lamblia surface interactions could assist in predicting transport and fate behavior in the environment and contribute to better design of water treatment processes, while the polymers identified in this work could find use in sensor applications and membrane filtration. PMID- 22303894 TI - Positive cooperativity in the template-directed synthesis of monodisperse macromolecules. AB - Two series of oligorotaxanes R and R' that contain -CH(2)NH(2)(+)CH(2)- recognition sites in their dumbbell components have been synthesized employing template-directed protocols. [24]Crown-8 rings self-assemble by a clipping strategy around each and every recognition site using equimolar amounts of 2,6 pyridinedicarboxaldehyde and tetraethyleneglycol bis(2-aminophenyl) ether to efficiently provide up to a [20]rotaxane. In the R series, the -NH(2)(+)- recognition sites are separated by trismethylene bridges, whereas in the R' series the spacers are p-phenylene linkers. The underpinning idea here is that in the former series, the recognition sites are strategically positioned 3.5 A apart from one another so as to facilitate efficient [pi...pi] stacking between the aromatic residues in contiguous rings in the rotaxanes and consequently, a discrete rigid and rod-like conformation is realized; these noncovalent interactions are absent in the latter series rendering them conformationally flexible/nondiscrete. Although in the R' series, the [3]-, [4]-, [8]-, and [12]rotaxanes were isolated after reaction times of <5-30 min in yields of 72 85%, in the R series, the [3]-, [4]-, [5]-, [8]-, [12]-, [16]-, and [20]rotaxanes were isolated in <5 min to 14 h in 88-98% yields. It follows that while in the R' series the higher order oligorotaxanes are formed in lower yields more rapidly, in the R series, the higher order oligorotaxanes are formed in higher yields more slowly. In the R series, the high percentage yields are sustained throughout, despite the fact that up to 39 components are participating in the template directed self-assembly process. Simple arithmetic reveals that the conversion efficiency for each imine bond formation peaks at 99.9% in the R series and 99.3% in the R' series. This maintenance of reaction efficiency in the R series can be ascribed to positive cooperativity, that is, when one ring is formed it aids and abets the formation of subsequent rings presumably because of stabilizing extended [pi...pi] stacking interactions between the arene units. Experiments have been performed wherein the dumbbell is starved of the macrocyclic components, and up to five times more of the fully saturated rotaxane is formed than is predicted based on a purely statistical outcome, providing a clear indication that positive cooperativity is operative. Moreover, it would appear that as the R series is traversed from the [3]- to the [4]- to the [5]rotaxane, the cooperativity becomes increasingly positive. This kind of cooperative behavior is not observed for the analogous oligorotaxanes in the R' series. The conventional bevy of analytical techniques (e.g., HR-MS (ESI) and both (1)H and (13)C NMR spectroscopy) help establish the fact that all the oligorotaxanes are pure and monodisperse. Evidence of efficient [pi...pi] stacking between contiguous arene units in the rings in the R series is revealed by (1)H NMR spectroscopy. Ion-mobility mass spectrometry performed on the R and R' series yielded the collisional cross sections (CCSs), confirming the rigidity of the R oligorotaxanes and the flexibility of the R' ones. The extended [pi...pi] stacking interactions are found to be present in the solid-state structures of the [3]- and [4]rotaxanes in the R series and also on the basis of molecular mechanics calculations performed on the entire series of oligomers. The collective data presented herein supports our original design in that the extended [pi...pi] stacking between contiguous arene units in the rings of the R series of oligorotaxanes facilitate an essentially rigid rod-like conformation with evidence that positive cooperativity improves the efficiency of their formation. This situation stands in sharp contrast to the conformationally flexible R' series where the oligorotaxanes form with no cooperativity. PMID- 22303895 TI - Comparison of lifestyle behaviors and related factors between Asian American and white adults with prediabetes. AB - This study compares lifestyle behaviors and related factors between Asian American and white adults with self-reported prediabetes and identifies covariates/predictors for regular physical activity and adequate intake of fruits/vegetables. Using data from the United States of America Behavioral Risk Factor Surveillance System, 302 Asian Americans and 9558 white adults were analyzed. There were no significant differences for participating in regular physical activity or consumption of adequate fruits/vegetables between the two groups. Overall, 40% of the respondents engaged in regular physical activity, whereas less than 25% reported an adequate intake of fruits/vegetables. In the adjusted models, compared to white, Asian Americans were less likely to have impaired physical (OR = 0.54, 95% CI: 0.36 0.80) or mental health (OR = 0.36, 95% CI: 0.21, 0.61), or cardiovascular diseases (OR = 0.59, 95% CI: 0.41, 0.87). The covariates/predictors that relate to the behaviors differed between the groups. We conclude that interventions to increase physical activity and healthy eating for Asian American and white adults with prediabetes should address the different covariates/predictors for each group. PMID- 22303896 TI - HTLV-I-associated myelopathy/tropical spastic paraparesis: semiautomatic quantification of spinal cord atrophy from 3-dimensional MR images. AB - BACKGROUND: Human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a disabling neurological disorder characterized by inflammatory changes in the spinal cord. We used a semiautomatic technique to quantify spinal cord volume from 3-dimensional MR images of patients with HAM/TSP. METHODS: Five patients and 5 matched healthy volunteers (HVs) underwent MRI of the cervical and thoracic spinal cord at 1.5 T. Quantification of the spinal cord volume was obtained from 3-dimensional MR images using a semiautomatic technique based on level sets. An unpaired t-test was used to assess statistical significance. RESULTS: Significant differences were found between mean spinal cord volume of HVs and HAM/TSP patients. The thoracic spinal cord volume was 14,050 +/- 981 mm(3) for HVs and 8,774 +/- 2,218 mm(3) for HAM/TSP patients (P = .0079), a reduction of 38%. The cervical spinal cord volume was 9,721 +/- 797 mm(3) for HVs and 6,589 +/- 897 mm(3) for HAM/TSP patients (P = .0079), a reduction of 32%. These results suggest that atrophy is evident throughout the spinal cord not routinely quantified. CONCLUSIONS: Semiautomatic spinal cord volume quantification is a sensitive technique for quantifying the extent of spinal cord involvement in HAM/TSP. PMID- 22303897 TI - Musings about beauty. AB - In this essay, I explore how cognitive science could illuminate the concept of beauty. Two results from the extensive literature on aesthetics guide my discussion. As the term "beauty" is overextended in general usage, I choose as my starting point the notion of "perfect form." Aesthetic theorists are in reasonable agreement about the criteria for perfect form. What do these criteria imply for mental representations that are experienced as beautiful? Complexity theory can be used to specify constraints on mental representations abstractly formulated as vectors in a high-dimensional space. A central feature of the proposed model is that perfect form depends both on features of the objects or events perceived and on the nature of the encoding strategies or model of the observer. A simple example illustrates the proposed calculations. A number of interesting implications that arise as a consequence of reformulating beauty in this way are noted. PMID- 22303898 TI - Clofarabine, cyclophosphamide and etoposide for the treatment of relapsed or resistant acute leukemia in pediatric patients. AB - Clofarabine is a promising new chemotherapeutic agent that is active in the treatment of pediatric acute leukemia. Forty children (16 with acute myeloid leukemia [AML], 24 with acute lymphoblastic leukemia [ALL]), aged 1-20 years (median 7.6 years) with relapsed or refractory ALL or AML were treated because of resistance to first-line treatment (n =5), or for first (n =22), second (n =11) or third relapse (n =2). They received clofarabine (40 mg/m(2)/day) associated with etoposide (100 mg/m(2)/day) and cyclophosphamide (440 mg/m(2)/day) administered as one or two induction cycles (5 days of chemotherapy) in an attempt to reach complete remission (CR) or CR without platelet recovery (CRp). This was followed by 1-3 consolidation cycles (4 days of chemotherapy) for a maximum of four cycles. Seven (44%) out of 16 and 10 (42%) out of 24 evaluable children with AML and ALL, respectively, responded to treatment. The most common adverse events were infections and gastrointestinal and hepatic toxicity. Thirteen (76%) out of 17 responders underwent hematopoietic stem cell transplant. The 24-month overall survival was 25%, while it was 59% among patients who responded to the first induction cycle. Our study suggests that this drug regimen is well tolerated and can be effective in heavily pretreated pediatric patients with relapsed or refractory acute leukemia. PMID- 22303899 TI - Acute lymphoblastic leukemia arising in post-polycythemic myelofibrosis: a rare entity. PMID- 22303900 TI - Boronic acid-protected gold clusters capable of asymmetric induction: spectral deconvolution analysis of their electronic absorption and magnetic circular dichroism. AB - Gold clusters protected by 3-mercaptophenylboronic acid (3-MPB) with a mean core diameter of 1.1 nm are successfully isolated, and their absorption, magnetic circular dichroism (MCD), and chiroptical responses in metal-based electronic transition regions, which can be induced by surface D-/L-fructose complexation, are examined. It is well-known that MCD basically corresponds to electronic transitions in the absorption spectrum, so simultaneous deconvolution analysis of electronic absorption and MCD spectra of the gold cluster compound is conducted under the constrained requirement that a single set of Gaussian components be used for their fitting. We then find that fructose-induced chiroptical response is explained in terms of the deconvoluted spectra experimentally obtained. We believe this spectral analysis is expected to benefit better understanding of the electronic states and the origin of the optical activity in chiral metal clusters. PMID- 22303901 TI - Effects of Jin-Ying-Tang on Staphylococcus aureus-induced mastitis in rabbit. AB - The present study was performed to investigate the effects of Jin-Ying-Tang (JYT), a Chinese herbal formula containing Lonicera japonica, Herba taraxaci, Fructus trichosanthis, Fructus forsythia, Radix et rhizoma rhei, Astragalus membranaceus, Angelica sinensis, on rabbit mastitis induced by Staphylococcus aureus. Suckling rabbits were challenged with 1.5 * 10(7) colony forming unit (CFU) of S. aureus at the base of the third pair teats, and they were treated and pretreated with JYT to detect the formula effects. The results showed that JYT could reduce the occurrence of Staphylococcal mastitis in rabbit model. To further investigate the action mechanism of JYT, we examined the leukocyte counts and inflammatory mediator levels such as TNF-alpha and IL-6 in blood and infected tissue. From histological study and blood analysis, we found that JYT could suppress leukocyte infiltration in infected mammary gland tissue and significantly inhibit the total leukocyte counts and lymphocytes (LYM), monocytes (MON) and granulocytes (GRA) fractions of leukocyte counts in blood. Enzyme linked immunosorbent assay (ELISA) results showed JYT significantly decreased the TNF-alpha and IL-6 concentrations in serum and mammary gland. The analysis of these data suggested that JYT effectively inhibited inflammatory responses to reduce the occurrence of mastitis in rabbit model. PMID- 22303902 TI - Reconstruction procedure for 3D micro X-ray absorption fine structure. AB - A new approach for chemical speciation in stratified systems using 3D Micro-XAFS spectroscopy is developed by combining 3D Micro X-ray Fluorescence Spectroscopy (3D Micro-XRF) and conventional X-ray Absorption Fine Structure Spectroscopy (XAFS). A prominent field of application is stratified materials within which depth-resolved chemical speciation is required. Measurements are collected in fluorescence mode which in general lead to distorted spectra due to absorption effects. Developing a reliable reconstruction algorithm for obtaining undistorted spectra for superficial and in-depth layers is proposed and validated. The developed algorithm calculates the attenuation coefficients of the analyte for the successive layers facilitating a new spectroscopic tool for three dimensionally resolved nondestructive chemical speciation. PMID- 22303903 TI - PDB ligand conformational energies calculated quantum-mechanically. AB - We present here a greatly updated version of an earlier study on the conformational energies of protein-ligand complexes in the Protein Data Bank (PDB) [Nicklaus et al. Bioorg. Med. Chem. 1995, 3, 411-428], with the goal of improving on all possible aspects such as number and selection of ligand instances, energy calculations performed, and additional analyses conducted. Starting from about 357,000 ligand instances deposited in the 2008 version of the Ligand Expo database of the experimental 3D coordinates of all small-molecule instances in the PDB, we created a "high-quality" subset of ligand instances by various filtering steps including application of crystallographic quality criteria and structural unambiguousness. Submission of 640 Gaussian 03 jobs yielded a set of about 415 successfully concluded runs. We used a stepwise optimization of internal degrees of freedom at the DFT level of theory with the B3LYP/6-31G(d) basis set and a single-point energy calculation at B3LYP/6 311++G(3df,2p) after each round of (partial) optimization to separate energy changes due to bond length stretches vs bond angle changes vs torsion changes. Even for the most "conservative" choice of all the possible conformational energies-the energy difference between the conformation in which all internal degrees of freedom except torsions have been optimized and the fully optimized conformer-significant energy values were found. The range of 0 to ~25 kcal/mol was populated quite evenly and independently of the crystallographic resolution. A smaller number of "outliers" of yet higher energies were seen only at resolutions above 1.3 A. The energies showed some correlation with molecular size and flexibility but not with crystallographic quality metrics such as the Cruickshank diffraction-component precision index (DPI) and R(free)-R, or with the ligand instance-specific metrics such as occupancy-weighted B-factor (OWAB), real-space R factor (RSR), and real-space correlation coefficient (RSCC). We repeated these calculations with the solvent model IEFPCM, which yielded energy differences that were generally somewhat lower than the corresponding vacuum results but did not produce a qualitatively different picture. Torsional sampling around the crystal conformation at the molecular mechanics level using the MMFF94s force field typically led to an increase in energy. PMID- 22303904 TI - Skiing efficiency versus performance in double-poling ergometry. AB - This study is on how leg utilisation may affect skiing efficiency and performance in double-poling ergometry. Three experiments were conducted, each with a different style of the double-poling technique: traditional with small knee range of-motion and fixed heels (TRAD); modern with large knee range-of-motion and fixed heels (MOD1) and modern with large knee range-of-motion and free heels (MOD2). For each style, motion data were extracted with automatic marker recognition of reflective markers and applied to a 3D full-body musculoskeletal simulation model. Skiing efficiency (skiing work divided by metabolic muscle work) and performance (forward impulse) were computed from the simulation output. Skiing efficiency was 4.5%, 4.1% and 4.1% for TRAD, MOD1 and MOD2, respectively. Performance was 111, 143 and 149 Ns for TRAD, MOD1 and MOD2, respectively. Thus, higher lower body utilisation increased the performance but decreased the skiing efficiency. These results demonstrate the potential of musculoskeletal simulations for skiing efficiency estimations. PMID- 22303905 TI - Flexible and dynamic thermal behavior of self-catenated [{Ni3(H2O)3(Bpa)4}(V6O18)].8H2O constructed from 10-c heterometallic inorganic organic clusters. AB - The hydrothermal treatment of Ni(NO(3))(2).6H(2)O, NaVO(3), and Bpa (1,2 Di(pyridyl)ethane) (C(12)H(12)N(2)) at 120 degrees C during 3 days leads to green single crystals of the title compound. The single crystal X-ray diffraction reveals that [{Ni(3)(H(2)O)(3)(Bpa)(4)}(V(6)O(18))].8H(2)O crystallizes in the monoclinic system, P2(1)/c space group, with a = 13.5536 (2), b = 19.0463 (2), c = 27.7435 (3) A, beta = 112.3880 (10) degrees , V = 6622(3) A(3), with R1(obs) = 0.0558, wR2(obs) = 0.1359, for 10278 observed reflections. The complexity of the crystal structure is based on different points, as the existence of: both "gauche" and "trans" conformations of the organic ligand, the [V(12)O(36)](-12) cycles, formed by 12 corner-sharing VO(4) tetrahedra, and, finally, the combination of both three-dimensional metal-organic and inorganic substructures, giving rise to a self-catenated highly connected net. The crystallization water molecules are semi-encapsulated in the channels along the [100] direction, and their loss gives rise to a dynamical and reversible structural contraction. Moreover, after the removal of the crystallization water molecules, the compound exhibits a negative thermal behavior in the 85-155 degrees C temperature range, and irreversible structural transformation due to the loss of coordinated water molecules up to 200 degrees C. The IR and UV-vis spectra were determined for the as-synthesized sample, after the removal of crystallization water molecules and after the irreversible transformation due to the loss of coordinated water molecules. The thermal evolution of chi(m) was adjusted to a magnetic model considering an isotropic dimer plus two Ni(II) d(8) isolated octahedra. PMID- 22303906 TI - Indices of language outcome 11 years after intrathecal chemotherapy for acute lymphoblastic leukemia: a sibling case-control study. AB - Studies are emerging that suggest that major language indices do not differentiate children treated for acute lymphoblastic leukemia (ALL) with risk adapted intrathecal chemotherapy (ITC) from control children matched on age, gender, and educational level. No study to date has controlled for cognitive environment, an important variable influencing language achievement and outcome. This case-control study applies the deconfounding principle by using a sibling as a control to investigate language outcomes in a male child 11 years after administration of ITC for ALL at the age of 2 years 3 months. A comprehensive behavioral language test battery failed to differentiate the siblings on current language performance when descriptively compared, but neurophysiological assessment revealed that the ITC-treated child required more time and elicited a smaller N400 component compared to his sibling during picture-word matching. The findings suggest that in the absence of pretreatment performance indices, comparison with sibling achievement may supplement what is known on posttreatment language skill development drawn from comparative studies using children matched on age, sex, and educational level drawn from the community. The study's findings offer pilot data of language outcomes following ITC beyond the early stage of survivorship. The benefits and limitations of using siblings in research where the cognitive environment is known to make an important contribution to skill development are discussed. PMID- 22303908 TI - Late gadolinium enhancement CMR in patients with tachycardia-induced cardiomyopathy caused by idiopathic ventricular arrhythmias. AB - BACKGROUND: Idiopathic ventricular arrhythmias in the form of monomorphic premature ventricular contractions (PVC) and/or ventricular tachycardia (VT) can cause tachycardia-induced cardiomyopathy (TICMP). The aim of this study was to determine the prevalence of late gadolinium enhancement (LGE) in patients with TICMP caused by idiopathic ventricular arrhythmias. METHODS: The study population consisted of 298 consecutive patients (174 F/124 M; mean age 45+/-17 years) with frequent PVCs and/or VT. TICMP was defined as left ventricular ejection fraction (LVEF) of <=50% in the absence of any detectable underlying heart disease and improvement of LVEF>=15% after effective treatment of index ventricular arrhythmia. RESULTS: Twenty-seven (9.1%) patients found to have LVEF<=50% and diagnosed as presumptive TICMP. Improvement in LVEF after effective treatment of index ventricular arrhythmia was observed in 22 of 27 patients (TICMP group; mean PVC burden of 30.8+/-9.9%). LVEF did not improve in five of 27 patients (primary cardiomyopathy group; mean PVC burden of 28.8+/-10.1%). LGE-cardiac magnetic resonance (CMR) imaging was performed in 19 of 22 patients with TICMP and one patient (5%) had LGE. All five patients with primary cardiomyopathy underwent LGE CMR imaging and four patients (80%) had LGE. CONCLUSIONS: LGE is a rare finding in patients with TICMP caused by idiopathic ventricular arrhythmias. LGE-CMR can be used in the diagnostic work-up of patients with TICMP. Further prospective studies are required to determine the role of LGE-CMR in predicting the recovery of left ventricular systolic dysfunction in patients with presumptive TICMP. PMID- 22303909 TI - Impact of benzodiazepines on posaconazole serum concentrations. A population based pharmacokinetic study on drug interaction. AB - OBJECTIVES: Posaconazole is broadly used for antifungal prophylaxis and therapy. Current data suggest a concentration-dependent effect. Unlike other triazoles, cytochrome P450 is not a relevant route of biotransformation for posaconazole but glucuronidation, which might lead to a different spectrum of drug interactions. For benzodiazepines, the major metabolic pathway involves oxidation, but some, including lorazepam and temazepam, undergo conjugation to glucuronic acid. RESEARCH DESIGN AND METHODS: Since 2006 serum levels of posaconazole are determined regularly in all hospitalized patients with intake of this triazole. Here we investigate posaconazole concentration at steady state in relation to the concomitant medication of benzodiazepines. RESULTS: While similar posaconazole concentrations were determined in samples obtained from patients receiving temazepam when compared to samples without any benzodiazepine, a relevant reduction of posaconazole concentration could be observed in patients with concomitant intake of lorazepam. This difference in posaconazole concentration with or without concomittant intake of lorazepam, was consistently significant for analyses of all samples (median 336 ng/ml vs. 585 ng/ml, p 0.001), for the average concentrations (569 ng/ml vs. 276 ng/ml, p 0.039), and for patients receiving a total daily dose of 800 mg posaconazole (292 ng/ml vs. 537 ng/ml, p 0.003). There was also a similar, but not significant trend for patients with a prophylactic dosage of 200 mg posaconazole three times daily (689 ng/ml vs. 512 ng/ml, p 0.186). CONCLUSIONS: In this retrospective study, analyzing blood samples from daily clinical practice of patients in various clinical settings and with different indications for antifungal therapy, concomitant medication of lorazepam was associated with decreased posaconazole concentrations. Therefore, lorazepam but not temazepam might induce posaconazole clearance by glucuronidation. PMID- 22303910 TI - Antihypertensive efficacy and tolerability of aliskiren/amlodipine single- pill combinations in patients with an inadequate response to aliskiren monotherapy. AB - Many patients with hypertension will require multiple antihypertensive drugs to achieve blood pressure (BP) control. This double-blind study evaluated the efficacy and safety of aliskiren/amlodipine single-pill combinations (SPCs) in patients with mild-to-moderate hypertension who were non-responsive to aliskiren monotherapy. After a 4-week run-in with aliskiren 300 mg, patients with mean sitting diastolic BP (msDBP) >= 90 and < 110 mmHg were randomized to oncedaily aliskiren/ amlodipine 300/10 mg or 300/5 mg, or aliskiren 300 mg for 8 weeks. Aliskiren/amlodipine SPCs provided significantly greater mean reductions in mean sitting systolic BP/msDBP (300/10 mg, 18.0/13.1 mmHg; 300/5 mg, 14.4/10.5 mmHg) than aliskiren 300 mg (6.4/5.8 mmHg) at week 8 endpoint. This represents additional mean reductions of 11.6/7.2 mmHg (300/10 mg) and 8.0/4.7 mmHg (300/5 mg) over aliskiren alone (both p < 0.0001). Significantly more patients achieved BP control ( < 140/90 mmHg) with aliskiren/amlodipine 300/10 mg (65.5%) and 300/5 mg (56.6%) than with aliskiren (31.5% both p < 0.0001). Aliskiren, alone and in combination with amlodipine, was well tolerated, with a slightly higher incidence of adverse events with SPCs (29.0-30.1%) than with monotherapy (22.7%). In conclusion, aliskiren/amlodipine SPCs offer an effective next step for patients who have an inadequate BP response to aliskiren alone. PMID- 22303911 TI - Efficacy and tolerability of aliskiren/amlodipine single-pill combinations in patients who did not respond fully to amlodipine monotherapyY. AB - Most patients with hypertension will require treatment with at least two antihypertensive agents to achieve blood pressure (BP) control. This double-blind study evaluated the efficacy and safety of aliskiren/amlodipine single-pill combination (SPC) therapy in patients with mild-to-moderate hypertension who are inadequately responsive to amlodipine monotherapy. Patients with mean sitting diastolic BP (msDBP) >= 90 and < 110 mmHg 110 mmHg after 4 weeks' treatment with amlodipine 10 mg were randomized to once-daily aliskiren/amlodipine 300/10 mg (n = 279) or 150/10 mg (n = 285) or amlodipine 10 mg monotherapy (n = 283) for 8 weeks. Aliskiren/amlodipine 300/10 and 150/10 mg SPCs provided significantly greater reductions in mean sitting systolic BP/msDBP (14.4/11.0 and 11.0/9.0 mmHg, respectively) than amlodipine 10 mg (8.2/7.2 mmHg) at week 8 endpoint. This represents additional mean reductions of 6.2/3.8 mmHg (300/10 mg) and 2.8/1.7 mmHg (150/10 mg) over amlodipine alone (all P < 0.01). Significantly more patients achieved BP control (< 140/90 mmHg) with aliskiren/amlodipine 300/10 mg (58.8%) than amlodipine 10 mg (38.4%; P < 0.0001). Aliskiren/amlodipine SPCs were generally well tolerated. In conclusion, aliskiren/amlodipine SPCs offers an effective option for management of patients who have an inadequate BP response to amlodipine alone. PMID- 22303912 TI - Soluble epoxide hydrolase inhibitors and cardiovascular diseases. AB - BACKGROUND: Epoxyeicosatrienoic acids (EETs) have been shown to play a role in cardiovascular protection by reducing ischemia reperfusion injury, producing anti inflammatory effects, and promoting angiogenesis. EETs are regulated through conversion to less active corresponding diols by soluble epoxide hydrolase (sEH). Inhibition of sEH enhances the beneficial properties of EETs and has been investigated as a possible treatment for cardiovascular diseases. CONTENT: sEH inhibitors (sEHIs) have anti-inflammatory effects by stabilizing anti inflammatory EETs. Additionally, sEHIs strongly inhibit and reverse cardiac hypertrophy. sEHIs have been shown to protect myocardial cells from ischemiareperfusion injury, treat atherosclerosis and prevent the development of hypertension. sEHIs promote blood vessels to release bradykinin via an EET mediated STAT3 signaling pathway to elicit tolerance to ischemia. SUMMARY: Inhibition of sEH has been shown to improve several aspects of cardiovascular diseases, including inflammation, hypertension, cardiac hypertrophy and atherosclerosis. For this reason, sEHIs are promising new pharmaceutical for the treatment of cardiovascular diseases. PMID- 22303913 TI - Current and prospective disease-modifying therapies for amyotrophic lateral sclerosis. AB - INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a devastating illness of unclear etiology affecting motor neurons. It causes unremitting muscle paralysis, atrophy and death usually within 3 - 5 years from diagnosis. The human and economic costs for those affected are sobering. To date, tremendous efforts have failed to find a cure. AREAS COVERED: An extensive literature search was undertaken using Medline and the Cochrane Systematic Review and Clinical Trial databases. Riluzole and investigational ALS drugs are discussed. Riluzole is the only approved disease-modifying therapy despite its modest effect on survival. Recent research has produced promising agents aimed at better disease control if not a cure. This review discusses agents targeting neuronal glutamate excitotoxicity, protein misfolding and accumulation, autophagy, apoptosis, mitochondrial dysfunction, free radical oxidative injury, immunomodulation, mutant mRNA counteraction, muscle physiology, neurotrophic factors and stem cell applications. The challenges in ALS drug development are highlighted. EXPERT OPINION: Riluzole should be used for patients with definite, probable, suspected or possible ALS by World Federation of Neurology diagnostic criteria. Systematic monitoring for hepatic dysfunction, neutropenia and other serious adverse effects should be done routinely as outlined. All ALS patients should consider genetic screening and enrollment in ALS trials guided by the data reviewed. PMID- 22303914 TI - Polymeric multilayer capsule-mediated vaccination induces protective immunity against cancer and viral infection. AB - Recombinant antigens hold high potential to develop vaccines against lethal intracellular pathogens and cancer. However, they are poorly immunogenic and fail to induce potent cellular immunity. In this paper, we demonstrate that polymeric multilayer capsules (PMLC) strongly increase antigen delivery toward professional antigen-presenting cells in vivo, including dendritic cells (DCs), macrophages, and B cells, thereby enforcing antigen presentation and stimulating T cell proliferation. A thorough analysis of the T cell response demonstrated their capacity to induce IFN-gamma secreting CD4 and CD8 T cells, in addition to follicular T-helper cells, a recently identified CD4 T cell subset supporting antibody responses. On the B cell level, PMLC-mediated antigen delivery promoted the formation of germinal centers, resulting in increased numbers of antibody secreting plasma cells and elevated antibody titers. The functional relevance of the induced immune responses was validated in murine models of influenza and melanoma. On a mechanistic level, we have demonstrated the capacity of PMLC to activate the NALP3 inflammasome and trigger the release of the potent pro inflammatory cytokine IL-1beta. Finally, using DC-depleted mice, we have identified DCs as the key mediators of the immunogenic properties of PMLC. PMID- 22303915 TI - Evaluation of educational program on osteoporosis awareness and prevention among nurse students in China. AB - This study assessed a targeted continuing osteoporosis educational program and investigated awareness and prevention of osteoporosis in Chinese female pre internship nurse students. A quasi-experimental study was conducted. The program was presented to 256 nurse students. The baseline knowledge score of the nurse students was low (9.78 +/- 3.13). They had inadequate osteoporosis health beliefs, self-efficacy and related behaviors. The educational program significantly augmented osteoporosis knowledge (Student's paired t = -13.42, P < 0.001), total osteoporosis health beliefs (Student's paired t = -4.46, P < 0.001), and the subscale (P < 0.001) except for the perceived barriers to exercising and calcium intake. Participants showed a significant increase in self efficacy (Student's paired t = -6.45, P < 0.001) post intervention. Those who completed the program were better prepared to prevent and manage osteoporosis. Additionally, nurse students became more concerned about bone health of family members, subjects and themselves because of attending the program. Results of this study reinforce the need for osteoporosis-related continuing education in nurse students before clinical internship. PMID- 22303916 TI - Highly luminescent InP/GaP/ZnS nanocrystals and their application to white light emitting diodes. AB - Highly stable and luminescent InP/GaP/ZnS QDs with a maximum quantum yield of 85% were synthesized by in situ method. The GaP shell rendered passivation of the surface and removed the traps. TCSPC data showed an evidence for the GaP shell. InP/GaP/ZnS QDs show better stability than InP/ZnS. We studied the optical properties of white QD-LEDs corresponding to various QD concentrations. Among various concentrations, the white QD-LEDs with 0.5 mL of QDs exhibited a luminous efficiency of 54.71 lm/W, Ra of 80.56, and CCT of 7864 K. PMID- 22303917 TI - Effect of environmental humidity on static foam stability. AB - The quality of foaming products (such as beer and shampoo) and the performance of industrial processes that harness foam (such as the froth flotation of minerals or the foam fractionation of proteins) depend upon foam stability. In this study, experiments are performed to study the effect of environmental humidity on the collapse of static foams. The dependency of the rate at which a foam collapses upon humidity is demonstrated, and we propose a hypothesis for bubble bursting due to Marangoni instability induced by nonuniform evaporation to help explain the dependency. This hypothesis is supported by direct experimental observations of the bursting process of isolated bubbles by high speed video recording and the thinning of isolated foam films under different values of humidity and temperature by microinterferometric methods. PMID- 22303919 TI - Manipulating energy transfer in copolymer-based nanocomposites by their controlled nanocaging and release of an ionic styryl dye: a case of an ultrasensitive pH sensor. AB - We report an interesting pH-tunable energy transfer between an acceptor ionic styryl dye 2-(4-(dimethylamino)styryl)-1-methylpyridinium iodide and a donor charge-transfer dye 1,8-naphthalimide in a vesicular medium. The polyethylene-b polyethylene glycol block copolymer intercalates with the sodium dodecyl sulfate anionic surfactant to form self-aggregated nanocomposites. These nanocomposites interact with the donor molecules in aqueous solution to form "vesicles", and the donor molecules become attached on the outer wall by hydrogen bonding. The acceptor molecules are observed to be loaded in the vesicular interior. By controlling the spectral overlap of the donor and acceptor molecules by changing the pH of the medium, the energy-transfer efficiency in vesicles has been studied. The efficiency of energy transfer in vesicular media (55%) is found to be less compared to that in aqueous media (80%) at pH 7. The fall in efficiency has been attributed to the perturbation imparted by the vesicular wall due to the good matching of the donor-acceptor distance with the wall thickness. At low pH, the efficiency shows an abrupt increase (95%) due to the release of the acceptor molecules from the vesicular medium causing subsequent reduction of donor acceptor separation and an increase of the spectral overlap at that pH. PMID- 22303920 TI - Alkali metal poisoning of a CeO2-WO3 catalyst used in the selective catalytic reduction of NOx with NH3: an experimental and theoretical study. AB - The alkali metal-induced deactivation of a novel CeO(2)-WO(3) (CeW) catalyst used for selective catalytic reduction (SCR) was investigated. The CeW catalyst could resist greater amounts of alkali metals than V(2)O(5)-WO(3)/TiO(2). At the same molar concentration, the K-poisoned catalyst exhibited a greater loss in activity compared with the Na-poisoned catalyst below 200 degrees C. A combination of experimental and theoretical methods, including NH(3)-TPD, DRIFTS, H(2)-TPR, and density functional theory (DFT) calculations, were used to elucidate the mechanism of the alkali metal deactivation of the CeW catalyst in SCR reaction. Experiments results indicated that decreases in the reduction activity and the quantity of Bronsted acid sites rather than the acid strength were responsible for the catalyst deactivation. The DFT calculations revealed that Na and K could easily adsorb on the CeW (110) surface and that the surface oxygen could migrate to cover the active tungsten, and then inhibit the SCR of NO(x) with ammonia. Hot water washing is a convenient and effective method to regenerate alkali metal poisoned CeW catalysts, and the catalytic activity could be recovered 90% of the fresh catalyst. PMID- 22303921 TI - Molecular basis of the mechanism of thiol oxidation by hydrogen peroxide in aqueous solution: challenging the SN2 paradigm. AB - The oxidation of cellular thiol-containing compounds, such as glutathione and protein Cys residues, is considered to play an important role in many biological processes. Among possible oxidants, hydrogen peroxide (H(2)O(2)) is known to be produced in many cell types as a response to a variety of extracellular stimuli and could work as an intracellular messenger. This reaction has been reported to proceed through a S(N)2 mechanism, but despite its importance, the reaction is not completely understood at the atomic level. In this work, we elucidate the reaction mechanism of thiol oxidation by H(2)O(2) for a model methanethiolate system using state of the art hybrid quantum-classical (QM-MM) molecular dynamics simulations. Our results show that the solvent plays a key role in positioning the reactants, that there is a significant charge redistribution in the first stages of the reaction, and that there is a hydrogen transfer process between H(2)O(2) oxygen atoms that occurs after reaching the transition state. These observations challenge the S(N)2 mechanism hypothesis for this reaction. Specifically, our results indicate that the reaction is driven by a tendency of the slightly charged peroxidatic oxygen to become even more negative in the product via an electrophilic attack on the negative sulfur atom. This is inconsistent with the S(N)2 mechanism, which predicts a protonated sulfenic acid and hydroxyl anion as stable intermediates. These intermediates are not found. Instead, the reaction proceeds directly to unprotonated sulfenic acid and water. PMID- 22303918 TI - Management of antimicrobial use in the intensive care unit. AB - Critically ill patients admitted to the intensive care unit (ICU) are frequently treated with antimicrobials. The appropriate and judicious use of antimicrobial treatment in the ICU setting is a constant clinical challenge for healthcare staff due to the appearance and spread of new multiresistant pathogens and the need to update knowledge of factors involved in the selection of multiresistance and in the patient's clinical response. In order to optimize the efficacy of empirical antibacterial treatments and to reduce the selection of multiresistant pathogens, different strategies have been advocated, including de-escalation therapy and pre-emptive therapy as well as measurement of pharmacokinetic and pharmacodynamic (pK/pD) parameters for proper dosing adjustment. Although the theoretical arguments of all these strategies are very attractive, evidence of their effectiveness is scarce. The identification of the concentration-dependent and time-dependent activity pattern of antimicrobials allow the classification of drugs into three groups, each group with its own pK/pD characteristics, which are the basis for the identification of new forms of administration of antimicrobials to optimize their efficacy (single dose, loading dose, continuous infusion) and to decrease toxicity. The appearance of new multiresistant pathogens, such as imipenem-resistant Pseudomonas aeruginosa and/or Acinetobacter baumannii, carbapenem-resistant Gram-negative bacteria harbouring carbapenemases, and vancomycin-resistant Enterococcus spp., has determined the use of new antibacterials, the reintroduction of other drugs that have been removed in the past due to toxicity or the use of combinations with in vitro synergy. Finally, pharmacoeconomic aspects should be considered for the choice of appropriate antimicrobials in the care of critically ill patients. PMID- 22303922 TI - Spirodela polyrhiza (L.) Sch. ethanolic extract inhibits LPS-induced inflammation in RAW264.7 cells. AB - OBJECTIVE: Spirodela polyrhiza (L.) Sch. is widely used in Korean traditional medicine. No previous work has investigated in detail the anti-inflammatory activities of S. polyrhiza or assessed in vitro their potential underlying mechanism(s). We assessed the effects of S. polyrhiza ethanolic extract (SPEE) on the production of inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and investigated some potential underlying mechanisms. Additionally, we performed simultaneous determination of seven flavonoids in S. polyrhiza by high-performance liquid chromatography (HPLC)-photodiode array (PDA). MATERIALS AND METHODS: RAW264.7 cells were subjected to 5, 10, 20, and 50 MUg/mL of SPEE for 1 h then treated with LPS for 24 h. Production of namely nitric oxide (NO), prostaglandin E(2) and cytokine levels were measured by the Griess reagent and ELISA, respectively. To investigate the underlying mechanisms of the anti-inflammatory activities of SPEE, expression of NO synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-kappaB) proteins were evaluated by western blot analysis. HPLC analysis was performed using a Gemini C(18) column at 40 degrees C and PDA detection at 340 nm. RESULTS: SPEE treatment significantly inhibited the LPS-induced production of NO, prostaglandin E(2), interleukin-6, and tumor necrosis factor-alpha and inhibited the expression of iNOS and COX-2 via attenuation of NF-kappaB p65 expression. The contents of the seven flavonoids in S. polyrhiza range from 0.25 to 8.77 mg/g. CONCLUSIONS: These results indicate that the anti-inflammatory activity of SPEE may be NF-kappaB p65 signaling. Also, the method will help to improve quality control of S. polyrhiza. PMID- 22303923 TI - Conventional wisdom: negotiating conventions of reference enhances category learning. AB - Collaborators generally coordinate their activities through communication, during which they readily negotiate a shared lexicon for activity-related objects. This social-pragmatic activity both recruits and affects cognitive and social cognitive processes ranging from selective attention to perspective taking. We ask whether negotiating reference also facilitates category learning or might private verbalization yield comparable facilitation? Participants in three referential conditions learned to classify imaginary creatures according to combinations of functional features-nutritive and destructive-that implicitly defined four categories. Remote partners communicated in the Dialogue condition. In the Monologue condition, participants recorded audio descriptions for their own later use. Controls worked silently. Dialogue yielded better category learning, with wider distribution of attention. Monologue offered no benefits over working silently. We conclude that negotiating reference compels collaborators to find communicable structure in their shared activity; this social-pragmatic constraint accelerates category learning and likely provides much of the benefit recently ascribed to learning labeled categories. PMID- 22303924 TI - Sulphur diagenesis in the sediments of the Kiel Bight, SW Baltic Sea, as reflected by multiple stable sulphur isotopes. AB - In this work, the biogeochemistry of marine sediments from the Kiel Bight, coastal SW Baltic Sea, is studied based on the abundance and isotopic composition of organic carbon and different forms of sedimentary sulphur. Active bacterial sulphate reduction, partly under sulphate-limiting conditions, is evident from paired delta(34)S and delta(18)O values of pore water sulphate. The resulting pore water sulphide is partly precipitated as acid-volatile iron sulphide and subsequently forms sedimentary pyrite, partly serves in later diagenetic sulphurisation of organic matter, or remains dissolved in the pore water, all evident from the respective delta(34)S values. Microbial sulphate turnover is associated with an apparent isotopic fractionation between dissolved sulphate and dissolved sulphide (Delta(34)S) that varies between 46 and 660/00. PMID- 22303926 TI - Targeting pre-mRNA splicing: a BACE-ic strategy for AD drug development? PMID- 22303927 TI - Usefulness of CT angiography for therapeutic decision making in thrombolyzing intubated patients with suspected basilar artery thrombosis. AB - BACKGROUND AND AIMS: Acute ischemic stroke (AIS) due to basilar artery thrombosis (BAT) causes high mortality and severe disability. Early neurological assessment and timely thrombolysis might improve outcome. BAT is difficult to diagnose due to wide spectrum of presentation and decreased conscious level. Emergency physicians often intubate BAT patients with airway compromise before arrival of stroke neurologist. We evaluated role of computerized tomography (CT) angiography (CTA) of brain and cervical arteries in early diagnosis of acute BAT in intubated patients and facilitating decision for thrombolysis. METHODS: Consecutive AIS patients presenting between 2007 and 2009 within 6 hours of symptom onset, with sudden deterioration in conscious level and intubation before assessment by neurologist, were included. All patients underwent brain CT and CTA. Outcomes were assessed at 3 months. RESULTS: Thrombolytic therapy, mainly intravenous tissue plasminogen activator (IV-TPA), was administered to 161 (8.4%) of 1,917 AIS patients during the study period. Acute BAT contributed 10.9% of our cohort. CTA was performed in 152 (94.4%) patients and the rest were excluded due to their impaired renal functions. Five patients (3 males, mean age 72 years) presenting with acute obtundation and airway compromise were intubated, sedated, and paralyzed before assessment by neurologist. CTA showed BAT in all. IV-TPA was initiated at 213 +/- 59 minutes in 4 patients while 1 received intraarterial thrombolysis at 13 hours. There was no intracranial hemorrhage. Mean length of hospital stay was 11.8 days. Despite severe stroke at presentation, good functional recovery at 3 months (modified Rankin scale [mRS] 1) occurred in 2 patients; mRS 4 in 1, and 2 died. CONCLUSION: In patients with BAT, intubated before assessment by neurologist, CTA might help in confirming the diagnosis and facilitating therapeutic decision making for initiating thrombolysis. PMID- 22303928 TI - Platinated DNA affects zinc finger conformation. Interaction of a platinated single-stranded oligonucleotide and the C-terminal zinc finger of nucleocapsid protein HIVNCp7. AB - This paper describes for the first time the intimate molecular details of the association between a platinated oligonucleotide and a zinc finger peptide. Site specific platination of the guanine in a single-stranded hexanucleotide gave {[Pt(dien)d(5'-TACGCC-3')], Pt(dien)(6-mer)} (II) characterized by mass spectrometry and (1)H nuclear magnetic resonance (NMR) spectroscopy. The work extends the study of platinum-nucleobase complex-zinc finger interactions using small molecules such as [Pt(dien)(9-EtGua)](2+) (I). The structure of the (34-52) C-terminal finger of HIV nucleocapsid protein HIVNCp7 (ZF1) was characterized by (1)H NMR spectroscopy and compared with that of the N-terminal single finger and the two-finger "intact" NCp7. Interaction of II with ZF1 results in significant changes in comparison to the "free" uncomplexed hexanucleotide; the major changes occurring for Trp37 resonances that are broadened and moved upfield, and other major shifts are for Gln45 (Hepsilon21, Hgamma3, Qbeta), Met46 (NH, Hgamma2), Lys47 (NH, Qgamma), and Glu50 (Hgamma2, Hgamma3). The Zn-Cys/His chemical shifts show only marginal deviations. The solution structures of ZF1 and the 6-mer-ZF1 and II-ZF1 adducts were calculated from the nuclear Overhauser effect spectroscopy-derived distance constraints. The DNA position in the II-ZF1 adduct is completely different than in the absence of platinum. Major differences are the appearance of new Met46-Cyt6 H5 and Trp37-Cyt5 H5 contacts but severe weakening of the Trp37-Gua4 contact, attributed to the steric effects caused by Gua4 platination, accompanied by a change in the position of the aromatic ring. The results demonstrate the feasibility of targeting specific ZF motifs with DNA tethered coordination compounds, such as Pt compounds and Co macrocycles, with implications for drug targetting and indeed the intimate mechanisms of DNA repair of platinated DNA. PMID- 22303929 TI - Totally laparoscopic management of gallstone ileus--technical report and review of the literature. AB - PURPOSE: Gallstone ileus is an uncommon complication of gallstone disease. It occurs in elderly patients in up to 25% of the cases. The management of gallstone ileus remains controversial. Open surgery has been the mainstay of treatment, but laparoscopic surgery has recently been used. In this study we report a case of an 87-year-old female patient with gallstone ileus who has been managed totally laparoscopically, detailing the technique and discussing the advantages of the laparoscopic approach with a review of the literature. METHODS: The pneumoperitoneum was established with a Veress needle. A three-port approach (one 5-mm and two 10-mm trocars) and a 30 degrees 10-mm laparoscope were used. The site of obstruction was 5 cm below the ligament of Treitz, and a single gallstone was identified. A 3-cm longitudinal enterotomy was created just above the site where the gallstone was located. An 8-cm-long gallstone was extracted. The enterotomy was closed transversely in a single layer of two sets of continuous sutures. RESULTS: The procedure was safely performed with all the advantages of minimally invasive surgery. Previous studies often described laparoscopically assisted procedures for the treatment of gallstone ileus, using a small abdominal incision. In recent years, some reports have been published on the efficacy of the totally laparoscopic approach in the management of gallstone ileus. CONCLUSIONS: Totally laparoscopic management of gallstone ileus could be safe and effective with suggested benefits for the elderly patients. PMID- 22303930 TI - Comparison of hybrid natural orifice transluminal endoscopic surgery and single port laparoscopic surgery for sentinel node basin dissection in a porcine model. AB - BACKGROUND: The aim of the present study was to use a porcine model to compare one- and two-port transvaginal natural orifice transluminal endoscopic surgery (NOTES) with single-port laparoscopic surgery (SPLS) for sentinel node basin dissection. STUDY DESIGN: Three groups (n=3 per group) of healthy female pigs were subjected to lymph node dissection. For hybrid NOTES, an endoscope was inserted via the transvaginal route. For SPLS, a 5-mm 30 degrees telescope with two-port laparoscopic instrument was inserted via the transumbilical port. The three methods were used to dissect the regions of the pig stomach that corresponded to four lymph node areas on the lesser curvature of the anterior wall and greater curvatures in humans. RESULTS: For two-port NOTES, SPLS, and one port NOTES, the overall rates of complete dissection of the lymph node stations were 91.6 %, 83%, and 50%, respectively (P>.05). The mean resected tissue weights were 49.3, 37.9, and 22.5 g, respectively (P=.03). The mean operation times for two-port NOTES (69.9 minutes) and SPLS (68 minutes) were shorter than that for one-port NOTES (99 min) (P>.05). CONCLUSION: Two-port NOTES and SPLS are more feasible than one-port NOTES for sentinel node basin dissection in a porcine model. One-port NOTES is difficult to perform and requires long operation times; however, we foresee this operation as becoming more common in the future. PMID- 22303931 TI - A rare cause of a relatively common neonatal emergency. AB - Malignant infantile osteopetrosis (MIOP) is a rare cause in the list of etiological factors of neonatal hypocalcemia in several textbooks. The most severe complication of MIOP is bone marrow suppression. The abnormal expansion of bone interferes with medullary haematopoiesis. Most children with this disease die within the first decade of life of secondary consequence of bone marrow failure. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for MIOP, an otherwise fatal disease. We present a neonate with MIOP that was further complicated with vitamin D deficiency. PMID- 22303933 TI - Cardiac resynchronization therapy with or without anatomical reverse remodeling does not affect defibrillation threshold. AB - BACKGROUND: Recent clinical trials have documented beneficial reverse-remodeling effects with cardiac resynchronization therapy (CRT). The aim of this study was to investigate the effect of CRT with or without reverse anatomical remodeling of the left ventricle on defibrillation threshold (DFT) levels in a prospective and consecutive group of patients with class II-IV systolic heart failure. METHODS: Study population consisted of 29 patients (14 women and 15 men; mean age 61+/-11 years old). All patients underwent baseline (within 24-hours of cardiac resynchronization therapy-defibrillator [CRT-D] implantation) and 6-month follow up DFT testing. Reverse anatomical remodeling of the left ventricle was defined as >=15% reduction in left ventricular end-systolic volume at the end of 6 months of follow-up compared to baseline. RESULTS: Baseline, average DFT was 8.8+/-5.9 J. Left ventricular end-diastolic volume was the only predictor of baseline DFT level (P=0.02) among the baseline demographics. Safety margin of at least 10 J was achieved in all patients. Average DFT at the end of 6 months of biventricular pacing was 9.2+/-6.9 J. One patient (3.4%) failed to have a safety margin of 10 J. Reverse anatomical remodeling was observed in 14 (48%) patients and did not have any effect on DFT level. There were no complications related to DFT testings. CONCLUSIONS: Baseline average DFT in patients undergoing CRT-D was <=10 J in our study. CRT-D with or without anatomical reverse remodeling does not affect DFT at the end of 6 months of follow-up. High DFT level at the end of 6 months of follow-up is rare (3.4%) among patients with current CRT-D devices. PMID- 22303934 TI - Phosphorescence imaging of living cells with amino acid-functionalized tris(2 phenylpyridine)iridium(III) complexes. AB - A series of nine luminescent cyclometalated octahedral iridium(III) tris(2 phenylpyridine) complexes has been synthesized, functionalized with three different amino acids (glycine, alanine, and lysine), on one, two, or all three of the phenylpyridine ligands. All starting complexes and final compounds have been fully analyzed by one-dimensional (1D) and two-dimensional (2D) NMR spectroscopy, and photophysical data have been obtained for all the mono-, bis-, and tri- substituted iridium(III) complexes. Cellular uptake and localization have been studied with flow cytometry and confocal microscopy, respectively. Confocal experiments demonstrate that all nine substituted iridium(III) complexes show variable uptake in the tumor cells. The monosubstituted iridium(III) complexes give the highest cellular uptake, and the series substituted with lysines shows the highest toxicity. This systematic study of amino acid-functionalized Ir(ppy)(3) complexes provides guidelines for further functionalization and possible implementation of luminescent iridium complexes, for example, in (automated) peptide synthesis or biomarker specific targeting. PMID- 22303935 TI - The skin-blanching assay. AB - The skin-blanching assay is used for the determination and bioequivalence of dermatologic glucocorticoids (GCs). The exact mechanism of the production of blanching is not fully understood, but it is considered that local vasoconstriction of the skin microvasculature and the consequent blood-flow reduction cause this phenomenon. Several factors influence skin blanching, including drug concentration, duration of application, nature of vehicle, occlusion, posture and location. The intensity of vasoconstriction can be measured in several ways: visual or quantitative methods, such as reflectance spectroscopy, thermography, laser Doppler velocimetry and chromametry. In literature, contradicting results in the correlation of the skin-blanching assay with different tests to determine GC sensitivity have been reported, limiting its clinical usefulness. PMID- 22303937 TI - Evaluation of mandibular hypoplasia in patients with hemifacial microsomia: a comparison between panoramic radiography and three-dimensional computed tomography. AB - OBJECTIVE: To compare the accuracy of three-dimensional computed tomography (3D CT) and panoramic radiography in the evaluation of mandibular hypoplasia in patients with hemifacial microsomia (HFM). DESIGN: Retrospective study of imaging data. Setting : Images selected from the archives of the University of Tokyo Hospital. SUBJECTS: Twenty patients with unilateral HFM who had undergone both panoramic radiography and 3D-CT in the same period. METHOD: Mandibular deformities were classified according to the Pruzansky classification; eight patients had Grade I deformity and 12 patients had Grade II deformity. Ramus heights were measured on both panoramic radiographs and 3D-CT. MAIN OUTCOME MEASURES: Magnification in panoramic radiographs and extent of mandibular asymmetry as estimated by the affected/unaffected side ratio based on two methods were examined. The Pearson product-moment correlation coefficient was used to estimate correlations between parameters. RESULTS: The magnification of ramus heights on panoramic radiographs showed large variations in Grade II patients. The affected/unaffected side ratio estimated by the two methods showed a strong correlation in Grade I patients (correlation coefficient 0.99; p < .0001). Conversely, a weak correlation was seen in Grade II patients (correlation coefficient 0.77; p = .0036), and affected/unaffected side ratios from panoramic radiographs were both over- and underestimated. CONCLUSIONS: The accuracy of evaluation using panoramic radiography was fairly reliable in Grade I patients. Conversely, accuracy was poor in Grade II patients, and evaluation using 3D-CT seems preferable. The combination of two methods with careful consideration is recommended for clinical applications. PMID- 22303936 TI - Drosophila as a model to study the genetic mechanisms of obesity-associated heart dysfunction. AB - Obesity and cardiovascular disease are among the world's leading causes of death, especially in Western countries where consumption of high caloric food is commonly accompanied by low physical activity. This lifestyle often leads to energy imbalance, obesity, diabetes and their associated metabolic disorders, including cardiovascular diseases. It has become increasingly recognized that obesity and cardiovascular disease are metabolically linked, and a better understanding of this relationship requires that we uncover the fundamental genetic mechanisms controlling obesity-related heart dysfunction, a goal that has been difficult to achieve in higher organisms with intricate metabolic complexity. However, the high degree of evolutionary conservation of genes and signalling pathways allows researchers to use lower animal models such as Drosophila, which is the simplest genetic model with a heart, to uncover the mechanistic basis of obesity-related heart disease and its likely relevance to humans. Here, we discuss recent advances made by using the power of the Drosophila as a powerful model to investigate the genetic pathways by which a high fat diet may lead to heart dysfunction. PMID- 22303938 TI - Keto and exomethylene pyranonucleosides as antitumor agents. AB - Nucleosides and their analogues take an important place in medicinal chemistry as the structural basis for the development of therapeutic agents. Recently, there has been a renewed interest in the synthesis of keto and exomethylene pyranonucleosides, due to their high cytotoxicity in vitro and powerful inhibitory action in vivo. Their mode of action probably involves their ability to act as acceptors in a Michael-addition mechanism, while it was revealed that 5 fluorouracil nucleosides represent novel prodrugs of 5-fluorouracil targeting thymidylate synthase. The present mini review summarizes the molecular design, chemical synthesis and biological activity of keto- and exomethylene pyranonucleoside analogues. PMID- 22303939 TI - Advances in the synthesis of bioactive unnatural amino acids and peptides. AB - The key role of proteins and amino acids in the structure and function of living matter has stimulated extensive studies. Modified amino acids with enhanced biological activity, proteolitic stability and bioavailability are of increasing interest in protein design and engineering as drug candidates. In the last few years, several efforts have been devoted to the synthesis of amino acids having unusual side chains and unnatural chirality, commonly referred to as "nonproteinogenic" or "unnatural" amino acids, even though some of them can be isolated from natural sources. In this review we describe recent advances in the amino acid side-chain transformations and backbone modifications by oxidative and fluorination procedures. PMID- 22303940 TI - Recent advance in the pharmacology of dihydropyrimidinone. AB - Dihydropyrimidinones (DHPMs) are a series of highly valuable small molecules possessing versatile pharmaceutical properties. Although the first one-pot synthesis of DHPMs had been reported more than 100 years ago, the fascinating achievement in DHPMs-based pharmacology during the past century promoted durative interests to the pharmacological and related studies of the scaffold, which lead to the discovery of many new biological functions of DHPMs. Recent pharmacological development on DHPMs-based molecules have been summarized in this review. PMID- 22303941 TI - Perspectives on medicinal properties of mangiferin. AB - Mango tree, Mangifera indica, has been cultivated in India and several other tropical countries for centuries, and it is a good source of compound 'mangiferin'. Mangiferin's xanthonoid structure with C-glucosyl linkage and polyhydroxy component is believed to be crucial for its free radical-scavenging ability leading to a potent antioxidant effect. A number of biological activities of mangiferin have been suggested, including antidiabetic and antiinflammatory abilities. These might be explained by its antioxidant ability as well as its ability to modulate several key inflammatory pathways. Mangiferin has also been shown to be an effective inhibitor of NF-kappaB signaling pathway. This partially explains its antiinflammatory ability and, additionally, points towards its anticancer potential. The anticancer effects of this compound are just beginning to emerge, and in this comprehensive review, we provide information on what we know about the chemistry and biological effects of mangiferin, which would likely create interest among researchers to design further mechanistic studies in order to better understand and exploit the biological activities of this compound. PMID- 22303942 TI - N-heterocyclic dronic acids: applications and synthesis. AB - Substituted hydroxymethylenebisphosphonic acid derivatives--either as dronic acids or their dronate sodium salts, are important pharmaceuticals in the treatment of diseases arising from excessive bone-resorption. Potential has also been identified in areas ranging from parasite-growth inhibition to immunological and cancer therapeutics. Representative clinically relevant N-heterocyclic derivatives include zoledronic and risedronic acids. The biochemical background and mechanism of action of these drugs are discussed, along with trends in structural development and future prospects. Synthetic routes to dronates are then summarized. The most popular route to valuable dronic acids involves the 3- component condensation of a substituted acetic acid, phosphorous acid, and phosphorus trichloride. However, the protocols recorded in the literature are very diverse. This review gives a critical account of reported methods, explores the contradictions and suggests a practical synthetic procedure after clarifying the inconsistencies described. Possible mechanisms of the reaction are also discussed. PMID- 22303943 TI - Novel target for Spinal Cord Injury Neuropathic Pain. AB - In the world today, millions of people suffer from spinal cord injury (SCI) with little known effective clinical therapy. Neuropathic pain (NP) is often the result of SCI, making clinical treatment difficult. Even though key mediators in the development of NP have been discovered, the pathogenesis is still unclear. Some of the key mediators in the formation of NP include the inflammatory process, cannabinoid receptors, matrix metalloproteases, and their tissue inhibitors. Animal models have shown promising results with these mediators, yet the clinical models are still unsuccessful. One such study focusing on matrix metalloproteases (MMPs) has produced encouraging results. The relationship between MMPs and their tissue inhibitors (TIMPs) plays a significant role in the pathogenesis and recovery of SCI and the CNS. Key factors that lead to the functional consequences of MMP activity are cellular localization, tissue distribution, and temporal pattern of MMP expression. Controlling the MMP activity and expression are transcription factors, signaling molecules, and inhibition by TIMPs. Studies saying that MMPs can be seen as contributors of tissue damage and as contributors in the repair mechanisms have provided a need to reexamine their roles after acute and chronic process like traumatic SCI and NP, respectively. In this review, we focus on novel findings related to NP mediators like cannabinoid receptors, MMPs, and TIMPs. We will also review current clinical findings; stressing areas that show great therapeutic potential. PMID- 22303944 TI - Small molecule kinase inhibitors as anti-cancer therapeutics. AB - Protein kinases have emerged as the most important class of targets in oncology drug discovery because of their major roles in regulating cellular growth and survival. At least, 11 kinase inhibitors have received FDA approval to be used as cancer treatments, and there are continuous efforts to bring more candidates from laboratory benches to the clinic. Although many protein kinase inhibitors directly interact with the ATP binding site, other can alter the kinase conformation to prevent productive ATP binding. Herein we discuss the different mechanisms of action of kinase inhibitors and provide classification of the inhibitors according to their binding sites. Some of these are allosteric inhibitors, ATP competitive inhibitors, protein substrate competitive inhibitors, and covalent bond forming inhibitors. This review provides a broad overview of the relation between mechanism of action and the issues of target selectivity and resistance. Special attention was given to the kinase inhibitors currently in clinical trials. PMID- 22303945 TI - A focus on glucose-mediated drug delivery to the central nervous system. AB - Drug delivery to the central nervous system (CNS) is a timely and challenging issue: 95 percent; of the pharmacological drugs cannot be delivered to the brain. This is mainly due to the blood-brain barrier (BBB), a highly selective boundary that hampers the passage of most compounds into the CNS. To overcome this problem, several approaches exist to deliver a therapeutic drug to the brain that takes into account not only the chemical properties of the drug but also the type of transport used at the BBB. One of those strategies is the glucose-mediated drug delivery which will be the focus of the present review. Glucose-mediated drug delivery requires the attachment of glycosyl moieties to a drug and the use of endogenous glucose transporters as a way to circumvent the blood-brain barrier. Glycosylated drugs display improved cell penetrability, enhanced biodistribution, stability and low toxicity. Examples such as glycosylation of ibuprofen and different opioids result in an enhanced central effect and will be discussed. PMID- 22303947 TI - Aldose reductase inhibitors and nanodelivery of diabetic therapeutics. AB - Nanotechnology is a rapidly emerging drug-delivery system that makes possible the controlled release of small molecules, and nanodelivery of therapeutic molecules using nanoparticles or nanogels represents a major improvement for more focused delivery of such therapeutic molecules. The delivery of insulin for the control of diabetes mellitus (DM) and aldose reductase inhibitor (ARI) for diabetic complications may provide better treatment of diabetes. A structural overview of aldose reductase including computational docking experiments with HAR-1, various ARIs, aldose-keto reductase, and nanodelivery of insulin, ARI's, and drug molecules are described. PMID- 22303948 TI - The mechanisms of anticancer agents by genistein and synthetic derivatives of isoflavone. AB - Genistein is the most abundant isoflavone in soybeans. It has exhibited diverse biological activities, among these, its anticancer effects is most noteworthy. Through regulating critical cell cycle genes, genistein can inhibit cancer cell growth in vivo and in vitro. It has been reported that genistein can inhibit activation of NF-kappaB and Akt signaling pathways to induce cell apopt1osis, both pathways are well known for their function to maintain a balance between cell survival and apoptosis. In order to find out more outstanding anticancer isoflavone agents, against cancers extended synthesis of genistein derivatives has been carried out. Some of these synthetic compounds demonstrated higher anticancer activity with lower doses. Based on these results, genistein and its synthetic derivatives may be an emerging new type of anticancer agents. PMID- 22303949 TI - Effects of elicitors, viticultural factors, and enological practices on resveratrol and stilbenes in grapevine and wine. AB - The ability of grapevine to activate defense mechanisms against some pathogens has been shown to be linked to the synthesis of stilbenes by the plant (inducible viniferins). Metabolized viniferins may also be produced or modified by extracellular enzymes released by the pathogen in an attempt to eliminate undesirable toxic compounds. Due to the important properties of resveratrol, there is increasing interest in producing foods with higher contents of this compound and higher nutritional value. The production of high resveratrol containing grapes and wines relies on quality-oriented viticulture (suitable terroirs, sustainable cultural practices) and wine-making technologies which avoid degradation of the compound. The technique of skin extraction and enzymatic hydrolysis of glucoside forms in wine-making plays an important role in resveratrol wine concentration. Other factors affecting its final concentration and balance in wine are conditions for promoting trans-cis isomerization of aglycones, the type of yeast used, and the presence of lactic bacteria with beta glucosidase activity. In general, the enological practices commonly used to stabilize wine after fermentation do not significantly affect resveratrol concentrations, which show considerable stability. PMID- 22303950 TI - Advances of paclitaxel formulations based on nanosystem delivery technology. AB - In this paper, an overview of recent advances of paclitaxel formulations based on nanosystems is provided. Paclitaxel is very effective in the treatment of various cancers especially ovarian and breast cancer, but it demonstrates poor aqueous solubility, which results in the difficulty challenging the development of paclitaxel parenteral formulations, so its clinical application is greatly restricted. The conventional paclitaxel formulation uses Cremophor EL and ethanol to solubilize paclitaxel, which could cause severe side effects. Nanotechnology has been widely exploited in the field of antitumor research, and paclitaxel is no exception. In recent decades, a series of novel formulations of paclitaxel based on nanotechnology have been developed, including albumin-bound paclitaxel, polymeric micelle-formulated paclitaxel, polymer-paclitaxel conjugates, liposome encapsulated paclitaxel etc. The common advantage shared with these novel injectable formulations is that they are developed based on nanotechnology and Cremophor EL-free. In addition, these nanoformulations can significantly reduce toxicities of paclitaxel and greatly promote its antitumor efficiency. PMID- 22303951 TI - Triorganotin(IV) complexes with biologically potent schiff bases: infrared, 119Sn spectral characteristics and antimicrobial applications. AB - This review paper has attempted information specific to the title compound. This survey of the literature data provides useful information about the design and stabilities of the triorganotin with biologically active ligands. Up to now, considerable efforts have been made to synthesize and characterize triorganotin(IV) schiff base complexes with the general formulae R3ML [R = organic group, M: Sn and L: schiff base] and many studies have been focused in order to understand bioassay results. Users with an interest in this substance are strongly encouraged for future research that this is still a very open field. PMID- 22303952 TI - Phosphodiesterase inhibitors in inflammatory bowel disease. AB - Inflammatory bowel disease (IBD) is fundamentally a relapsing and remitting disease appearing in forms of ulcerative colitis (UC) or Crohn's disease (CD) with a non-well-known etiology. With the hope to prevent adverse drug events and to increase the efficacy of therapies for IBD, in the recent years, other than new monoclonal antibodies such as infliximab, the novel phosphodiesterase inhibitors (PDEIs) have been introduced. Among PDE4Is, rolipram, OPC-6535, mesopram, roflumilast and tetomilast have shown beneficial effects in experimental colitis. Unfortunately until now, human studies have not been successful in showing significant superiority of PDE4Is in the treatment of IBD. Parallel with discovery of PDE4Is and their anti-inflammatory properties, inhibiting other PDE isoenzymes in immune and proinflammatory cells is on the way. PDE7Is have shown synergistic effect with PDE4Is and they may act similar to PDE3Is in experimental settings. Sildenafil as the PDE5I has shown good effects in experimental colitis by balancing oxidant-antioxidant status. Although the present data about PDE superfamily and their specific roles in gastrointestinal tract is limited but inhibitors of PDE4, PDE5 and PDE7 seem good candidates as the next generation of effective drugs. The synergistic anti-inflammatory effect of PDE4Is and PDE7Is is also important. PMID- 22303953 TI - Water oxidation at hematite photoelectrodes: the role of surface states. AB - Hematite (alpha-Fe(2)O(3)) constitutes one of the most promising semiconductor materials for the conversion of sunlight into chemical fuels by water splitting. Its inherent drawbacks related to the long penetration depth of light and poor charge carrier conductivity are being progressively overcome by employing nanostructuring strategies and improved catalysts. However, the physical-chemical mechanisms responsible for the photoelectrochemical performance of this material (J(V) response) are still poorly understood. In the present study we prepared thin film hematite electrodes by atomic layer deposition to study the photoelectrochemical properties of this material under water-splitting conditions. We employed impedance spectroscopy to determine the main steps involved in photocurrent production at different conditions of voltage, light intensity, and electrolyte pH. A general physical model is proposed, which includes the existence of a surface state at the semiconductor/liquid interface where holes accumulate. The strong correlation between the charging of this state with the charge transfer resistance and the photocurrent onset provides new evidence of the accumulation of holes in surface states at the semiconductor/electrolyte interface, which are responsible for water oxidation. The charging of this surface state under illumination is also related to the shift of the measured flat-band potential. These findings demonstrate the utility of impedance spectroscopy in investigations of hematite electrodes to provide key parameters of photoelectrodes with a relatively simple measurement. PMID- 22303954 TI - Influence of the molecular environment on phosphorylated amino acid models: a density functional theory study. AB - A protein environment can affect the structure and charge distribution of substrate molecules. Here, the structure and partial charges were studied for different phosphorylated amino acid models in varying environments using density functional theory. The three systems investigated, acetyl phosphate, methyl phosphate, and p-tolyl phosphate are representative models for aspartyl phosphate, serine or threonine phosphate, and tyrosine phosphate, respectively. Combined with the CPCM continuum model, explicit HF and H(2)O molecules were added in order to model environmental effects and interactions that may occur in a protein matrix. We show how the different interactions affect the scissile P O(R) bond and that the elongation can be explained by an anomeric effect. An increasing scissile bond length will result in transfer of negative charge to the leaving group and in a widening of the angle between the terminal oxygens of the phosphate molecule, features that can expose the phosphate group to attacking nucleophiles. Lastly, calculations were performed on the active site of the Ca(2+)-ATPase E2P intermediate, which provide an example of how a protein environment facilitates the formation of a destabilized ground state. PMID- 22303955 TI - Impact of technology-based care and management systems on aged care outcomes in Australia. AB - This study determined the impact of a computerized care documentation system on client outcomes, regulatory compliance, and staff workloads after 3 years of use. The survey was conducted at an 800-bed aged care facility, and staff using the computerized care system were invited to participate (n = 112). The survey was an adapted version of the Nurses Computer Attitudes to Technology Inventory, which was refined to make it relevant to the aged care workplace. Four multiple regression models were produced, assessing the impact of the computerized care management system on staff and workload; time; accuracy, and regulatory data; and resident care. The analysis showed that the perceived benefits of the computerized system were influenced by personal attitudes towards computer use and feelings of empowerment related to the computer system. Even those with poor computer skills and feelings of insecurity about using computers believed that there were significant benefits to be gained by using the system. This result has implications with regards to the training and recruitment of staff in the aged care sector, as facilities introduce computerized care systems. PMID- 22303957 TI - PCBs and OCPs on a east-to-west transect: the importance of major currents and net volatilization for PCBs in the Atlantic Ocean. AB - Air-water exchange gradients of selected polychlorinated biphenyl (PCB) congeners across a large section of the tropical Atlantic suggested net volatilization of PCBs to the atmosphere. Only for the higher chlorinated PCB 153 and hexachlorobenzene (HCB) were gradients near equilibrium detected. The use of passive samplers also enabled the detection of dichlorodiphenyltrichloroethane (DDT) and its transformation products across the tropical Atlantic, indicating net deposition. There were clear differences between the southern and northern hemisphere apparent in terms of atmospheric concentrations: Once the ship moved from the southern into the northern hemisphere air, concentrations of HCB and other organochlorine pesticides increased several-fold. For large swaths of the tropical Atlantic Ocean, neither PCB nor organochlorine pesticide dissolved concentrations varied much longitudinally, probably due to efficient mixing by ocean currents. In selected samples, dissolved concentrations reflected the influence of river plumes and major ocean currents far away from the continents. Dissolved concentrations of PCBs 28, 52, 101, 118, and HCB increased in the Amazon plume and the Gulf Stream. While the Amazon plume flushed only a few kg of PCBs and HCB, the Gulf Stream is potentially delivering tons of PCBs into the North Atlantic annually. PMID- 22303956 TI - Microsomal glutathione transferase 1 protects against toxicity induced by silica nanoparticles but not by zinc oxide nanoparticles. AB - Microsomal glutathione transferase 1 (MGST1) is an antioxidant enzyme located predominantly in the mitochondrial outer membrane and endoplasmic reticulum and has been shown to protect cells from lipid peroxidation induced by a variety of cytostatic drugs and pro-oxidant stimuli. We hypothesized that MGST1 may also protect against nanomaterial-induced cytotoxicity through a specific effect on lipid peroxidation. We evaluated the induction of cytotoxicity and oxidative stress by TiO(2), CeO(2), SiO(2), and ZnO in the human MCF-7 cell line with or without overexpression of MGST1. SiO(2) and ZnO nanoparticles caused dose- and time-dependent toxicity, whereas no obvious cytotoxic effects were induced by nanoparticles of TiO(2) and CeO(2). We also noted pronounced cytotoxicity for three out of four additional SiO(2) nanoparticles tested. Overexpression of MGST1 reversed the cytotoxicity of the main SiO(2) nanoparticles tested and for one of the supplementary SiO(2) nanoparticles but did not protect cells against ZnO induced cytotoxic effects. The data point toward a role of lipid peroxidation in SiO(2) nanoparticle-induced cell death. For ZnO nanoparticles, rapid dissolution was observed, and the subsequent interaction of Zn(2+) with cellular targets is likely to contribute to the cytotoxic effects. A direct inhibition of MGST1 by Zn(2+) could provide a possible explanation for the lack of protection against ZnO nanoparticles in this model. Our data also showed that SiO(2) nanoparticle induced cytotoxicity is mitigated in the presence of serum, potentially through masking of reactive surface groups by serum proteins, whereas ZnO nanoparticles were cytotoxic both in the presence and in the absence of serum. PMID- 22303958 TI - Gold nanocluster-based fluorescent probes for near-infrared and turn-on sensing of glutathione in living cells. AB - In this study, a novel Au nanocluster (NC)-based fluorescent sensor has been designed for near-infrared (NIR) and turn-on sensing of glutathione (GSH) in both living cells and human blood samples. The large Stokes-shifted (140 nm) fluorescent Au NCs with NIR emission and long-wavelength excitation have been rapidly synthesized for 2 h by means of a microwave-assisted method in aqueous solution. The addition of Hg(II) leads to an almost complete emission quenching (98%) of Au NCs because of the interaction of Hg(II) and Au(I) on the surface of Au NCs. After introducing GSH to the Au NC-Hg(II) system, a more than 20 times fluorescent enhancement is obtained because of the preferable affinity of GSH with Hg(II). Under optimum conditions, the fluorescence recovery is linearly proportional to the concentration of GSH between 0.04 and 16.0 MUM and the detection limit is as low as 7.0 nM. This Au NC-based sensor with high sensitivity and low spectral interference has been proven to facilitate biosensing applications. PMID- 22303959 TI - Did the Chinese have a change of heart? AB - In their "The Prevalence of Mind-Body Dualism in Early China," Slingerland and Chudek use a statistical analysis of the early Chinese corpus to argue for Weak Folk Dualism (WFD). We raise three methodological objections to their analysis. First, the change over time that they find is largely driven by genre. Second, the operationalization of WFD is potentially misleading. And, third, dating the texts they use is extremely controversial. We conclude with some positive remarks. PMID- 22303961 TI - Beliefs about medications in asthmatic children presenting to emergency department and their parents. AB - OBJECTIVE: The aim of our study was to assess the relationship of beliefs about medications questionnaire (BMQ) scores of asthmatic children presenting to the emergency department and their parents with asthma severity parameters. METHODS: Eighty children with asthma presenting to the emergency department with acute asthma findings and their mothers were enrolled in the study. BMQ was applied to all parents and children older than 7 years of age. Asthma severity clinical score was recorded. RESULTS: The mean age of children (39 males, 41 females) was 49.1 +/- 42.8 months. Parent necessity and concerns scores were significantly correlated with their counterparts in children (r = 0.74 and r = 0.60, respectively). Difference between necessity and concerns scores was correlated between parents and children (r = 0.60, p = .002). Child's necessity score was significantly correlated with respiratory severity score (r = -0.43, p = .036). CONCLUSION: BMQ necessity and concerns scores of asthmatic children in the emergency department and their parents are correlated with asthma severity. Although not assessed in this study, this result may be attributed to the relationship of necessity and concerns with drug adherence. Therefore, increasing the knowledge about asthma medications in asthmatic children and their parents may contribute to asthma control and decrease their emergency visits with acute asthma findings. PMID- 22303960 TI - A G-rich element forms a G-quadruplex and regulates BACE1 mRNA alternative splicing. AB - beta-Site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is the transmembrane aspartyl protease that catalyzes the first cleavage step in the proteolysis of the APP to the amyloid beta-protein (Abeta), a process involved in the pathogenesis of Alzheimer disease. BACE1 pre-mRNA undergoes complex alternative splicing, the regulation of which is not well understood. We identified a G-rich sequence within exon 3 of BACE1 involved in controlling splice site selection. Mutation of the G-rich sequence decreased use of the normal 5' splice site of exon 3, which leads to full-length and proteolytically active BACE1, and increased use of an alternative splice site, which leads to a shorter, essentially inactive isoform. Nuclease protection assays, nuclear magnetic resonance, and circular dichroism spectroscopy revealed that this sequence folds into a G-quadruplex structure. Several proteins were identified as capable of binding to the G-rich sequence, and one of these, heterogeneous nuclear ribonucleoprotein H, was found to regulate BACE1 exon 3 alternative splicing and in a manner dependent on the G-rich sequence. Knockdown of heterogeneous nuclear ribonucleoprotein H led to a decrease in the full-length BACE1 mRNA isoform as well as a decrease in Abeta production from APP, suggesting new possibilities for therapeutic approaches to Alzheimer's disease. PMID- 22303962 TI - Binding of filamentous actin to anthrax toxin receptor 1 decreases its association with protective antigen. AB - ANTXR1 is a type I membrane protein that binds the protective antigen (PA) component of anthrax toxin. The cytosolic domain of ANTXR1 has a novel actin binding region that influences the interaction of the ectodomain with PA. Here, we have investigated features of the cytosolic domain of ANTXR1 that reduce the association of the receptor with PA. We mutated a stretch of conserved acidic amino acids adjacent to the actin-binding region and found that the mutation increased the affinity for monomeric actin in vitro. ANTXR1 bearing this mutation exhibited increased association with the cytoskeleton and bound less PA compared to the wild-type receptor, confirming the inverse correlation between the two interactions. To determine whether binding of actin is sufficient to regulate the ectodomain, we replaced the actin-binding region of ANTXR1 with that from the yeast protein abp140 and with the WH2 domain of WAVE2. Although both of these domains bound monomeric actin in vitro, only the sequence from abp140 reduced binding of PA to a hybrid receptor. The actin binding regions of ANTXR1 and abp140, but not the WH2 domain, colocalized with actin stress fibers, which suggested that filamentous actin regulates ANTXR1. Consistent with this notion, disruption of actin filaments using latrunculin A increased the amount of PA bound to cells. This work provides evidence that cytoskeletal dynamics regulate ANTXR1 function. PMID- 22303963 TI - Determination of three steroidal saponins from Ophiopogon japonicus (Liliaceae) via high-performance liquid chromatography with mass spectrometry. AB - A simple and accurate analytical method was developed for simultaneous quantification of three steroidal saponins in the roots of Ophiopogon japonicus via high-performance liquid chromatography (HPLC) with mass spectrometry (MS) in this study. Separation was performed on a Tigerkin C(18) column and detection was performed by mass spectrometry. A mobile phase consisted of 0.02% formic acid in water (v/v) and 0.02% formic acid in acetonitrile (v/v) was used with a flow rate of 0.5 mL min(-1). The quantitative HPLC-MS method was validated for linearity, precision, repeatability, stability, recovery, limits of detection and quantification. This developed method provides good linearity (r >0.9993), intra- and inter-day precisions (RSD <4.18%), repeatability (RSD <5.05%), stability (RSD <2.08%) and recovery (93.82-102.84%) for three steroidal saponins. It could be considered as a suitable quality control method for O. japonicus. PMID- 22303964 TI - The unique features of traumatic brain injury in children. review of the characteristics of the pediatric skull and brain, mechanisms of trauma, patterns of injury, complications, and their imaging findings--part 2. AB - Traumatic brain injury (TBI) is a major cause of morbidity and mortality in children. The unique biomechanical, hemodynamical, and functional characteristics of the developing brain and the age-dependent variance in trauma mechanisms result in a wide range of age specific traumas and patterns of brain injuries. Detailed knowledge of the main primary and secondary pediatric injuries, which enhance sensitivity and specificity of diagnosis, will guide therapy and may give important information about the prognosis. In recent years, anatomical but also functional imaging methods have revolutionized neuroimaging of pediatric TBI. The purpose of this article is (1) to comprehensively review frequent primary and secondary brain injuries and (2) to give a short overview of two special types of pediatric TBI: birth related and nonaccidental injuries. PMID- 22303967 TI - Circulating tumor cells: highlight on practical implications. AB - Circulating tumor cells (CTCs) are cells of presumed epithelial origin, whose prognostic and predictive value in metastatic cancer patients has recently been demonstrated. To date, the count of CTCs through the CellSearch(r) system represents a valid approach for monitoring disease status in patients with metastatic colorectal, breast, and prostate cancer; in these cancer types, a rise in the CTC count at any time during treatment predicts a poor outcome. Nevertheless, the clinical utility of monitoring CTC counts remains controversial, and what to do when CTC counts rise during therapy still remains an unanswered question. In this report, we suggest how to integrate CTC counts with their molecular characterization to better translate biologic information obtained on CTCs into daily clinical practice. PMID- 22303968 TI - From antioxidant chelators to site-activated multi-target chelators targeting hypoxia inducing factor, beta-amyloid, acetylcholinesterase and monoamine oxidase A/B. AB - Chelators hold great promise as disease-modifying drugs for Alzheimer's therapy, and recent research efforts have focused on designing multi-target chelators with increased targeting and efficacy through rational drug design. In this review, we discuss our research studies on the rational design of new multi-target chelators with the potential not only to simultaneously modulate several disease-related targets, but also contain features designed to improve the BBB permeability, increase the brain targeting, and minimize potential side effects. These new chelators include neuroprotective chelators with brain selective monoamine oxidase (MAO) A/B inhibitory activity, acetylcholinesterase (AChE) inhibitors with site-activated chelating and neurogenesis activity, and AChE-MAO A/B inhibitors with site-activated chelating and neurogenesis activity. PMID- 22303969 TI - Chinese herbs for dementia diseases. AB - In the last twenty years a considerable body of information has accumulated on the chemical constituents of Chinese herbs and their therapeutic potential. Our evaluation/systematic review [1, 2] of well-designed, randomized double blind controlled trials on Chinese herbal medicines beneficial for the improvement of cognitive function revealed a range of either single herbs or herbal mixtures that provided neuroprotective benefits. Oxidative stress may directly initiate neurodegeneration and herbal antioxidant neuroprotection is considered as a preventative and therapeutic approach. We encountered Acoris gramineus rhizome (AGR), Panax ginseng, Polygala tenuifolia and Poria cocos as the four most frequently used herbs as single/herbal mixtures that were associated with positive cognitive enhancing outcomes. This review focuses on the evidence of their medicinal effects attributed to those constituents present in relatively high concentration. PMID- 22303970 TI - Redox chemistry of green tea polyphenols: therapeutic benefits in neurodegenerative diseases. AB - Evidence for the medicinal and health benefits of polyphenols in green tea for the prevention of chronic diseases such as heart disease, various types of cancer and neurodegenerative diseases is advancing. Their in vivo effectiveness and molecular mechanisms are difficult to elucidate and remain a challenging task. We review the redox responsiveness and amyloid protein perturbation biophysical properties of the major green tea polyphenol constituent (-)- epigallocatechin-3 gallate [EGCG]. PMID- 22303971 TI - A survey of peptides with effective therapeutic potential in Alzheimer's disease rodent models or in human clinical studies. AB - Alzheimer's disease (AD) is a devastating neurodegenerative disorder and the most common cause of dementia. Today, only palliative therapies are available. The pathological hallmarks of AD are the presence of neurofibrillary tangles and amyloid plaques, mainly composed of the amyloid-beta peptide (Abeta), in the brains of the patients. Several lines of evidence suggest that the increased production and/or decreased cleavage of Abeta and subsequent accumulation of Abeta oligomers and aggregates play a fundamental role in the disease progress. Therefore, substances which bind to Abeta and influence aggregation thereof are of great interest. A wide range of Abeta binding peptides were investigated to date for therapeutic purposes. Only very few were shown to be effective in rodent AD models or in clinical studies. Here, we review those peptides and discuss their possible mechanisms of action. PMID- 22303974 TI - QSAR applications during last decade on inhibitors of acetylcholinesterase in Alzheimer's disease. AB - This article reviews multi-criteria QSAR applications on Acetylcholinesterase inhibitors as palliative drugs for Alzheimer's Disease, published in the period 2001-2011. It includes QSAR models for different series of compounds, comparative studies, and advances in methodologies. This period is marked by a shift in focus from palliative treatment to pathogenesis. However, we believe that research into palliative treatment should continue. More comparative studies are desirable. In order to facilitate comparative and general studies on Acetylcholinesterase inhibitors, a standard experimental protocol for measuring an inhibitor's potency is needed. Finally, we recommend chemists to work closely with system and molecular biologists. PMID- 22303979 TI - Chronically transfused pediatric sickle cell patients are protected from cardiac iron overload. AB - Iron overload is a major toxicity of chronic transfusions. Myocardial iron overload is associated with cardiac dysfunction. Cardiac and liver magnetic resonance imaging (MRI) was performed on 14 chronically transfused sickle cell disease (SCD) and non-sickle cell disease (non-SCD) patients seen at Vanderbilt Children's Hospital from 1 January 2000 to 10 March 2010. Retrospective review was conducted to assess cardiac T2*, liver T2*, ventricular dimensions and function, echocardiogram, length of transfusion, hemoglobin, and ferritin measurements. Ten patients had SCD and 4 had non-SCD, including alpha thalassemia, beta-thalassemia, and Diamond-Blackfan anemia. Cardiac T2* was normal in all SCD patients (mean 39 +/- 12 ms), but abnormal in 3 of 4 non-SCD patients (mean 11.8 +/- 2.4 ms). Liver T2* was similar between SCD (mean 6.2 +/- 1.6 ms) and non-SCD patients (mean 5.9 +/- 1.9 ms), and did not correlate with serum ferritin. Comparing SCD and non-SCD patients with similar transfusion duration, SCD patients had normal cardiac T2* and non-SCD patients had abnormal cardiac T2*. No patients had cardiomyopathy, but ventricular dilatation was common among SCD patients. Chronically transfused pediatric SCD patients are relatively spared of myocardial iron overload, which is unlikely to be due to lower total body iron burden in SCD patients than non-SCD patients. PMID- 22303981 TI - Mechanism and diversity of the erythromycin esterase family of enzymes. AB - Macrolide antibiotics such as azithromycin and erythromycin are mainstays of modern antibacterial chemotherapy, and like all antibiotics, they are vulnerable to resistance. One mechanism of macrolide resistance is via drug inactivation: enzymatic hydrolysis of the macrolactone ring catalyzed by erythromycin esterases, EreA and EreB. A genomic enzymology approach was taken to gain insight into the catalytic mechanisms and origins of Ere enzymes. Our analysis reveals that erythromycin esterases comprise a separate group in the hydrolase superfamily, which includes homologues of uncharacterized function found on the chromosome of Bacillus cereus, Bcr135 and Bcr136, whose three-dimensional structures have been determined. Biochemical characterization of Bcr136 confirms that it is an esterase that is, however, unable to inactivate macrolides. Using steady-state kinetics, homology-based structure modeling, site-directed mutagenesis, solvent isotope effect studies, pH, and inhibitor profiling performed in various combinations for EreA, EreB, and Bcr136 enzymes, we identified the active site and gained insight into some catalytic features of this novel enzyme superfamily. We rule out the possibility of a Ser/Thr nucleophile and show that one histidine, H46 (EreB numbering), is essential for catalytic function. This residue is proposed to serve as a general base in activation of a water molecule as the reaction nucleophile. Furthermore, we show that EreA, EreB, and Bcr136 are distinct, with only EreA inhibited by chelating agents and hypothesized to contain a noncatalytic metal. Detailed characterization of these esterases allows for a direct comparison of the resistance determinants, EreA and EreB, with their prototype, Bcr136, and for the discussion of their potential connections. PMID- 22303982 TI - Mitotic rate and subcutaneous involvement are prognostic factors for survival after recurrence in patients with only locoregional skin metastasis as the first site of recurrence from cutaneous melanoma. AB - BACKGROUND: Few reports on literature give detailed figures on prognostic factors of locoregional skin recurrence in cutaneous melanoma. OBJECTIVE: The aim of this study was to evaluate clinical and histological prognostic factors following development of locoregional cutaneous metastasis as the only progression site from melanoma. METHODS: Data from 1327 stage I and II melanoma patients who visited Instituto Valenciano de Oncologia and Consorcio Hospital General Universitario de Valencia from 2000 to 2010 were documented in a prospective manner. During follow up, 112 (8.4%) of them developed recurrent disease. A retrospective analysis revealed a subset of 36 patients with locoregional cutaneous metastases as a first event. RESULTS: Significant prognostic factors in the univariate analysis were Breslow thickness, tumor mitotic rate and the presence subcutaneous involvement of the skin metastasis. After multivariate analysis the independent predictive factors for survival after recurrence were tumor mitotic rate (hazard ratio [HR]: 8.6; 95% CI: 1.0-77.2) and subcutaneous involvement of the skin metastasis (HR: 4.3; 95% CI: 1.0-18.5). CONCLUSION: The survival after recurrence of melanoma patients that has relapsed with only locoregional cutaneous metastasis depends on the mitotic rate of the primary tumor and the subcutaneous involvement of the metastasis. PMID- 22303983 TI - Japanese women's attitudes towards routine ultrasound screening during pregnancy. AB - Because there are few published studies from Eastern countries concerning women's experiences of prenatal ultrasound scans, this study investigated this topic in 238 Japanese women in three different prenatal settings. A cross-sectional questionnaire of 33 items was administered to 261 women at 14-37 weeks gestation with no known obstetrical risk, after their ultrasounds. The main reasons for the ultrasounds were evaluation of fetal growth (100%, n = 238); obstetrical conditions (n = 228, 96%); and fetal abnormalities (91%, n = 217). With increasing maternal age, participants worried more about obstetric problems or fetal abnormalities. Many were interested in fetal viability in early pregnancy, and obstetric problems or fetal abnormality in late pregnancy. While most (n = 234, 98%) looked forward to having scans, the majority (n = 235, 99%) wanted to know if their baby had an anomaly, and 72% (n = 171) worried about the detection of abnormalities. Only 50% (n = 118) had obtained information from their care provider. To assist with women's decision-making, prenatal care providers should provide quality information and understand the factors that influence women's concerns. PMID- 22303984 TI - Exploring the possibilities of cryogenic cooling in liquid chromatography for biological applications: a proof of principle. AB - The possibilities to use cryogenic cooling to trap components in liquid chromatography was investigated. In a first step, van 't Hoff plots were measured with a reversed-phase column using the temperature control unit of a conventional high performance liquid chromatography (HPLC) system to gain insight in the retention behavior of proteins at low temperatures. It was estimated that retention factors in the range of k = 10(4) could be achieved at T = -20 degrees C for lysozyme, indicating that temperature is a usable parameter to trap components in LC. In a next step, trapping experiments were carried out on a nano LC system, equipped with a UV-detector, using a commercial reversed-phase column. An in-house built setup, allowing cooling of a segment of the column down to temperatures below T = -20 degrees C, was used to trap components. Experiments were conducted under isocratic and gradient conditions with methanol as organic solvent. It is demonstrated that, by thermally trapping and elution of components, an enhanced S/N ratio and decreased peak widths can be obtained. At the same time, a significant increase in pressure drop occurs during the cooling process. Limitations and benefits of the technique are further discussed. PMID- 22303985 TI - Self-organizable vesicular columns assembled from polymers dendronized with semifluorinated Janus dendrimers act as reverse thermal actuators. AB - The synthesis and structural analysis of polymers dendronized with self assembling Janus dendrimers containing one fluorinated and one hydrogenated dendrons are reported. Janus dendrimers were attached to the polymer backbone both from the hydrogenated and from the fluorinated parts of the Janus dendrimer. Structural analysis of these dendronized polymers and of their precursors by a combination of differential scanning calorimetry, X-ray diffraction experiments on powder and oriented fibers, and electron density maps have demonstrated that in both cases the dendronized polymer consists of a vesicular columnar structure containing fluorinated alkyl groups on its periphery. This vesicular columnar structure is generated by a mechanism that involves the intramolecular assembly of the Janus dendrimers into tapered dendrons followed by the intramolecular self assembly of the resulting dendronized polymer in a vesicular column. By contrast with conventional polymers dendronized with self-assembling tapered dendrons this new class of dendronized polymers acts as thermal actuators that decrease the length of the supramolecular column when the temperature is increased and therefore, are called reverse thermal actuators. A mechanism for this reversed process was proposed. PMID- 22303986 TI - Resistance to trophic neurite outgrowth of sensory neurons exposed to insulin. AB - Insulin offers trophic support through receptors expressed widely on peripheral neurons. In this work, we studied whether peripheral sensory neurons demonstrate resistance to its trophic properties, a property relevant during type 2 diabetes mellitus or following supraphysiological therapy. Insulin receptors were not only localized to neuronal membranes and cytoplasm but also had a unique, previously unrecognized localization to neuronal nuclei. We confirmed that nanomolar doses increased neurite outgrowth of adult sensory neurons, but in response to micromolar doses of insulin, even following a brief 2-h exposure, survival and outgrowth of neurites were blunted. Neurons exposed to picomolar insulin concentrations in their media for 5 days had resistance to the impact of later nanomolar doses of insulin. Using a stripe assay seeded with insulin, neurites were more likely to reject higher doses of insulin. Insulin down-regulated mRNAs of the insulin receptor beta subunit and up-regulated levels of GSK-3beta, both potential mechanisms of insulin resistance, while down-regulating the protein expression of pAkt and pGSK-3beta. Overall, these studies identify neuronal nuclear targeting of insulin and evidence for insulin-induced resistance to its trophic properties. The findings have implications for the understanding of the actions of insulin in the treatment of diabetes and neurological disorders. PMID- 22303988 TI - Vestibular regeneration--experimental models and clinical implications. AB - Therapies aimed at the protection and/or regeneration of inner ear hair cells are of great interest, given the significant monetary and quality of life impact of balance disorders. Different viral vectors have been shown to transfect various cell types in the inner ear. The past decade has provided tremendous advances in the use of adenoviral vectors to achieve targeted treatment delivery. Several routes of delivery have been identified to introduce vectors into the inner ear while minimizing injury to surrounding structures. Recently, the transcription factor Atoh1 was determined to play a critical role in hair cell differentiation. Adenoviral-mediated overexpression of Atoh1 in culture and in vivo has demonstrated the ability to regenerate vestibular hair cells by causing transdifferentiation of neighbouring epithelial-supporting cells. Functional recovery of the vestibular system has also been documented following adenoviral induced Atoh1 overexpression. Experiments demonstrating gene transfer in human vestibular epithelial cells reveal that the human inner ear is a suitable target for gene therapy. PMID- 22303989 TI - Design and synthesis of novel 1',3'-dioxolane 5'-deoxyphosphonic acid purine analogues as potent antiviral agents. AB - Electronic parameters of 1',3 '-oxygen play significant roles in steering the conformation of nucleoside phosphonic acid analogues. To investigate the relationship of two oxygen atoms with antiviral enhancement, novel 1',3 ' dioxolane 5 '-deoxyphosphonic acid purine analogues were synthesized via de novo acyclic stereoselective route from acrolein and glycolic acid. The synthesized nucleoside phosphonic acid analogues 14 and 19 were subjected to antiviral screening against several viruses, such as HIV-1, HSV-1, HSV-2, and HCMV. The guanine analogue 19 exhibits in vitro anti-HIV-1 activity similar to that of 9-[2 (phosphonomethoxy)ethyl]adenine (PMEA) in MT-4 cells. PMID- 22303990 TI - Design and synthesis of dephosphono DNA analogues containing 1,2,3-triazole linker and their UV-melting studies with DNA/RNA. AB - This article describes the synthesis of 3'/5' linked 1,2,3-triazolyl dithymidine derivatives, their incorporation into oligonucleotides, and evaluation of their thermal stabilities toward complementary DNA/RNA. PMID- 22303991 TI - Correlated tissue expression of genes of cytoplasmic and mitochondrial nucleotide metabolisms in normal tissues is disrupted in transformed tissues. AB - Cells maintain dual metabolic pathways to provide substrates for the replication of mitochondrial and nuclear DNA. These pathways involve two separate sets of genes in the nuclear DNA, with one set encoding proteins targeted to the mitochondrion. However, the cytoplasmic and mitochondrial metabolisms are capable of communication through the transport of deoxyribonucleosides and deoxyribonucleotides between the two subcellular compartments. Cytoplasmic and mitochondrial deoxyribonucleoside triphosphate concentrations are strongly correlated in normal cells but not in transformed cells. We were therefore interested in comparing the interactions in normal and transformed tissues between the corresponding cytoplasmic and mitochondrial metabolisms that produce deoxyribonucleoside triphosphates. We conducted an analysis of gene expression data in normal and transformed human tissues obtained from the UniGene database for a selected set of genes for proteins involved in nucleoside salvage in either the cytoplasm or mitochondria. We also included ribonucleotide reductase in our analysis due to its importance in generating deoxyribonucleoside triphosphates. This analysis revealed a large number of highly significant positive correlations between the tissue expression profiles of the genes of the mitochondrial and cytoplasmic pathways in normal tissues, indicating that in normal tissues, the two metabolisms coordinately generate deoxyribonucleoside triphosphates. In transformed tissues, this correlation structure was disrupted. Multiple correlations involving the mitochondrial nucleoside kinase gene DGUOK were statistically significantly different between normal and transformed tissues, suggesting that control of DGUOK expression relative to other cytoplasmic genes is important in transformed tissues. PMID- 22303992 TI - Synthesis, DNA binding, and cleavage studies of Co(III) complexes with fused aromatic NO/NN-containing ligands. AB - Four new Co(III) complexes, namely [Co(cq)(3)](PF(6))(3), [Co(phen)(2)(cq)](PF(6))(3), [Co(bnp)(3)] (PF(6))(3), and [Co(phen)(2)(bnp)](PF(6))(3) (where cq = chromeno[2,3-b]quinoline, phen = 1,10 phenanthroline and bnp = dibenzo[b,g][1,8]naphthyridine), were synthesized and structurally characterized. Spectroscopic data suggested an octahedral geometry for all the complexes. Binding studies of these complexes with double-stranded (ds)DNA were analyzed by absorption spectra, viscosity, and thermal denaturation studies. The results revealed that the metal complex intercalates into the DNA base stack as intercalator. The oxidative cleavage activities of the complexes were studied with supercoiled pUC19 DNA using gel electrophoresis and the results show that the complexes have potent nuclease activity. PMID- 22303993 TI - On model ensemble analyses of nonmonotonic data. AB - Mammalian ribonucleotide reductase (RNR) activity has been reported to be nonmonotonic in ATP. If many nonlinear models are to be fitted to such data automatically as part of a model search process, use of the same initial parameter values across all models can lead to too many poor fitting, monotonic least squares fits, i.e., false model rejections. We propose that such fits can be rescued by using as initial parameter estimates the final estimates of neighboring models that do have nonmonotonic fits; here models are neighbors if complexes that they represent differ by at most one ligand. We use this approach to show that troughs in RNR activity versus ATP can be fitted similarly well by models that do or do not demand a third ATP binding site. PMID- 22303995 TI - Protection/Deprotection of surface activity and its applications in the controlled release of liposomal contents. AB - The micelles of two tripropargylammonium-functionalized cationic surfactants were cross-linked by a disulfide-containing diazido cross-linker in the presence of Cu(I) catalysts. With multiple residual alkyne groups on the surface, the resulting surface cross-linked micelles (SCMs) were postfunctionalized by reaction with 2-azidoethanol and an azido-terminated poly(ethylene glycol), respectively, via the alkyne-azide click reaction. The water-soluble nanoparticles obtained had low surface activity due to the buried hydrophobic tails. Cleavage of the disulfide cross-links by dithiothreitol (DTT) exposed the hydrophobic tails and resumed surface activity of the "caged" surfactants within 2 min after DTT addition. The controlled breakage of the SCMs was used to lower the surface tension of aqueous solutions and trigger the release of liposomal contents on demand. PMID- 22303997 TI - Leukoencephalopathies in mitochondrial disorders: clinical and MRI findings. AB - The second most frequently affected organ in mitochondrial disorders (MIDs) is the central nervous system (CNS). One of the most frequent CNS abnormalities on imaging is the affection of the white matter (WMLs) for which the term, leukoencephalopathies in mitochondrial disorders (LEM), is proposed. The morphology of LEM on imaging is quite variable even within the same type of MID and the same family. LEM can be a subtle or prominent feature on imaging and may go along with or without clinical neurologic or neuropsychological manifestations. WMLs are most likely due to the underlying metabolic defect of the respiratory chain or concomitant oxidative stress, resulting in neuronal death and replacement of neurons by glial cells. WMLs in MIDs frequently give rise to misinterpretation, particularly if the mitochondrial defect is not evident in organs other than the CNS or if the presence of WMLs does not induce consideration of a MID as a differential. The diagnosis of a LEM requires the diagnosis of an MID, the detection of WMLs on imaging, and the exclusion of all possible differentials. Because the presence of LEM has an impact on the prognosis of an MID, all MID patients should undergo cerebral imaging even in the absence of clinical CNS manifestations. PMID- 22303996 TI - Current status of body composition assessment in sport: review and position statement on behalf of the ad hoc research working group on body composition health and performance, under the auspices of the I.O.C. Medical Commission. AB - Quantifying human body composition has played an important role in monitoring all athlete performance and training regimens, but especially so in gravitational, weight class and aesthetic sports wherein the tissue composition of the body profoundly affects performance or adjudication. Over the past century, a myriad of techniques and equations have been proposed, but all have some inherent problems, whether in measurement methodology or in the assumptions they make. To date, there is no universally applicable criterion or 'gold standard' methodology for body composition assessment. Having considered issues of accuracy, repeatability and utility, the multi-component model might be employed as a performance or selection criterion, provided the selected model accounts for variability in the density of fat-free mass in its computation. However, when profiling change in interventions, single methods whose raw data are surrogates for body composition (with the notable exception of the body mass index) remain useful. PMID- 22303998 TI - Sleep quality and sleepiness in persons with implantable cardioverter defibrillators: outcome from a clinical randomized longitudinal trial. AB - BACKGROUND: Patients receiving an implantable cardioverter defibrillator (ICD) report various types and degree of sleep disruptions, but little is known regarding their characteristics, duration, and associated factors. The purposes of this study were: (1) to describe the effect of a psychoeducational intervention on sleep quality and daytime sleepiness, (2) to describe patterns of sleep over time, and (3) to identify predictors of poor sleep in an ICD population. METHODS: A randomized longitudinal intervention trial was designed to test the effects of a psychoeducational intervention, which included a sleep education and counseling session in patients receiving their initial ICD. Patients (n=236; 75% men; mean age 58.4 [+/-11.2] from the PsychoEducationAl Intervention for ICD PatiEnts (PEACE) trial comprised the study population. Variables related to sleep were measured by the Pittsburgh Sleep Quality Inventory (PSQI) and Epworth Sleepiness Scale (ESS). RESULTS: No psychoeducational intervention effects on sleep outcomes were observed. However, 67.2% of the patients reported poor sleep quality at baseline, and 56.8% had low sleep quality at 6 months based on PSQI scores>5; one-third (32.6%) were excessively sleepy based on ESS scores>=10 at 6 months. Anxiety, depression, physical function, pain intensity, and pain severity were all highly correlated to each other across time. Female gender was a significant covariate for the PSQI. New York Heart Association (NYHA) class was a significant covariate for sleepiness (Epworth). CONCLUSIONS: Low sleep quality and daytime sleepiness are found at time of insertion and over time in patients with ICD. Female gender, higher NYHA class, as well as two latent factors encompassing increased anxiety, depressive symptoms, and decreased physical function and increased pain, were significant predictors of poor sleep quality and sleepiness over time. These data help identify those at higher risk for sleep problems after ICD. PMID- 22303999 TI - Adult cleft lip repair under local anesthesia: an effective technique in resource poor settings. AB - Objective : In developing countries there are many adults with unrepaired cleft lip deformities. These countries often lack the equipment and personnel to provide general anesthesia for all patients; therefore, a technique for repair under local anesthesia would be useful. Method : A retrospective review was performed of 22 adolescent/adult patients on whom primary cleft lip repair was performed under local anesthesia in Bamako, Mali, in 2008 and 2009. Inclusion criteria for this technique were age greater than 12 with unilateral or bilateral deformity and ability to understand and tolerate the procedure under local anesthesia alone. Exclusion criteria included cardiopulmonary disease or inability to tolerate the procedure while awake. Demographic information and outcome data were collected including total time in the operating room, surgical time, and day of discharge. Results : Twenty-two primary cleft lip repairs were completed in 12 male and 10 female patients. Mean age was 22.3 years and mean weight was 50 kg. Overall, mean total operating room time was 145 minutes. Mean operating room time was significantly (p < .01) longer in 2008 (159 minutes) than in 2009 (114 minutes). Although mean surgical time was 110 minutes, there was a similar significant (p = .03) decrease from 2008 (119 minutes) to 2009 (91 minutes). All patients tolerated the procedure without requiring intubation or intravenous sedation, and all were discharged the same day. Conclusion : Cleft lip repair in adults under local anesthesia is safe and effective. Improvements in technique and efficiency have made this valuable in developing countries. PMID- 22304000 TI - Hybrid quantum/classical simulations of the vibrational relaxation of the amide I mode of N-methylacetamide in D2O solution. AB - Hybrid quantum/classical molecular dynamics (MD) is applied to simulate the vibrational relaxation (VR) of the amide I mode of deuterated N-methylacetamide (NMAD) in aqueous (D(2)O) solution. A novel version of the vibrational molecular dynamics with quantum transitions (MDQT) treatment is developed in which the amide I mode is treated quantum mechanically while the remaining degrees of freedom are treated classically. The instantaneous normal modes of the initially excited NMAD molecule (INM(0)) are used as internal coordinates since they provide a proper initial partition of the system in quantum and classical subsystems. The evolution in time of the energy stored in each individual normal mode is subsequently quantified using the hybrid quantum-classical instantaneous normal modes (INM(t)). The identities of both the INM(0)s and the INM(t)s are tracked using the equilibrium normal modes (ENMs) as templates. The results extracted from the hybrid MDQT simulations show that the quantum treatment of the amide I mode accelerates the whole VR process versus pure classical simulations and gives better agreement with experiments. The relaxation of the amide I mode is found to be essentially an intramolecular vibrational redistribution (IVR) process with little contribution from the solvent, in agreement with previous theoretical and experimental studies. Two well-defined relaxation mechanisms are identified. The faster one accounts for ~40% of the total vibrational energy that flows through the NMAD molecule and involves the participation of the lowest frequency vibrations as short-life intermediate modes. The second and slower mechanism accounts for the remaining ~60% of the energy released and is associated to the energy flow through specific mid-range and high-frequency modes. PMID- 22304002 TI - Evaluating rare earth element availability: a case with revolutionary demand from clean technologies. AB - The future availability of rare earth elements (REEs) is of concern due to monopolistic supply conditions, environmentally unsustainable mining practices, and rapid demand growth. We present an evaluation of potential future demand scenarios for REEs with a focus on the issue of comining. Many assumptions were made to simplify the analysis, but the scenarios identify some key variables that could affect future rare earth markets and market behavior. Increased use of wind energy and electric vehicles are key elements of a more sustainable future. However, since present technologies for electric vehicles and wind turbines rely heavily on dysprosium (Dy) and neodymium (Nd), in rare-earth magnets, future adoption of these technologies may result in large and disproportionate increases in the demand for these two elements. For this study, upper and lower bound usage projections for REE in these applications were developed to evaluate the state of future REE supply availability. In the absence of efficient reuse and recycling or the development of technologies which use lower amounts of Dy and Nd, following a path consistent with stabilization of atmospheric CO(2) at 450 ppm may lead to an increase of more than 700% and 2600% for Nd and Dy, respectively, over the next 25 years if the present REE needs in automotive and wind applications are representative of future needs. PMID- 22304003 TI - Development and preliminary validation of the Asthma Intensity Manifestations Score (AIMS) derived from Asthma Control Test, FEV(1), fractional exhaled nitric oxide, and step therapy assessments. AB - OBJECTIVE: Inherent asthma severity is difficult to assess clinically. The purpose of this study was to develop an Asthma Intensity Manifestations Score (AIMS) as a surrogate for asthma severity. METHODS: Three hundred and four patients treated with inhaled corticosteroids completed the Asthma Control Test (ACT), underwent spirometry, and fractional exhaled nitric oxide (FENO) testing, and reported their current medications. These parameters (defined as ACT < 16, forced expiratory volume in 1 second [FEV(1)] < 80% predicted, FENO > 50 ppb, and Expert Panel Report [EPR3] step care level >3) were related to prior year outcomes to develop the AIMS and to follow-up year outcomes to validate it. RESULTS: FENO was independently related to prior year short-acting beta agonist (SABA) >= 7 (odds ratio [OR] 2.9); ACT (OR 4.9), FEV(1) (OR 3.3), and step care (OR 3.9) were independently related to prior year systemic corticosteroid (SCS) >= 2. Thus, all the four items were chosen for the AIMS (0-4 points). AIMSs were linearly related to follow-up year SABA >= 7, any SCS, SCS >= 2, and emergency hospital care (all p < .01). Compared to patients with AIMSs <2, patients with AIMSs >=2 were at more than a fourfold greater risk of requiring >=2 SCS in the following year and were at a 2-2.8-fold greater risk of experiencing other adverse outcomes during that time period. CONCLUSIONS: The AIMS is linearly related to future year adverse asthma outcomes. Further studies will be necessary to confirm its utility as a surrogate for asthma severity in clinical practice and clinical research. PMID- 22304004 TI - Euglobal-like compounds from the genus Eugenia. AB - Two regioisomeric meroterpenoids, Eugenial A and B, have been isolated from the fruits of Eugenia multiflora and their structures established on the basis of NMR evidences. They possess a phloroglucinol-monoterpene structure similar to the euglobals occurring in the sister genus Eucaliptus. A simple method to distinguish between regioisomeric pairs was pointed. PMID- 22304005 TI - Molecular insight into the role of the leucine residue on the L2 loop in the catalytic activity of caspases 3 and 7. AB - Various apoptotic signals can activate caspases 3 and 7 by triggering the L2 loop cleavage of their proenzymes. These two enzymes have highly similar structures and functions, and serve as apoptotic executioners. The structures of caspase 7 and procaspase 7 differ significantly in the conformation of the loops constituting the active site, indicating that the enzyme undergoes a large structural change during activation. To define the role of the leucine residue on the L2 loop, which shows the largest movement during enzyme activation but has not yet been studied, Leu168 of caspase 3 and Leu191 of caspase 7 were mutated. Kinetic analysis indicated that the mutation of the leucine residues sometimes improved the Km but also greatly decreased the kcat, resulting in an overall decrease in enzyme activity. The tryptophan fluorescence change at excitation/emission = 280/350 nm upon L2-L2' loop cleavage was found to be higher in catalytically active mutants, including the corresponding wild-type caspase, than in the inactive mutants. The crystal structures of the caspase 3 mutants were solved and compared with that of wild-type. Significant alterations in the conformations of the L1 and L4 loops were found. These results indicate that the leucine residue on the L2 loop has an important role in maintaining the catalytic activity of caspases 3 and 7. PMID- 22304006 TI - Antiproliferative activity of trans-avicennol from Zanthoxylum chiloperone var. angustifolium against human cancer stem cells. AB - Zanthoxylum chiloperone var. angustifolium root bark was studied with the aim of finding novel molecules able to overcome cancer stem cell chemoresistance. Purification of a methanol-soluble extract resulted in the isolation of a known pyranocoumarin, trans-avicennol (1). Compound 1 demonstrated antiproliferative activity on glioma-initiating cells, whereas it was inactive on human neural stem cells. trans-Avicennol (1) activated the MAPK/ERK pathway and was also evaluated for its ability to inhibit the enzyme indoleamine-2,3-dioxygenase. PMID- 22304007 TI - Ewing sarcoma: biology-based therapeutic perspectives. AB - Ewing sarcoma, a rare malignancy of childhood and adolescence, has attracted wide research interest. Tumor-specific chromosomal translocations generate aberrant EWS-ETS transcription factors, which alter intracellular signaling networks through gene and protein expression and are considered to be the primary tumor initiating event. Ewing sarcoma therefore offers insights into principle molecular mechanisms of cancer development and maintenance. Still, despite long standing research, biology-based targeted treatment strategies for Ewing sarcoma are only beginning to emerge. This article provides an overview of the biological basis and putative targeted treatment options. PMID- 22304009 TI - Long-term survival results of pediatric rhabdomyosarcoma patients: a single center experience from Turkey. AB - The characteristics and clinical outcomes of 409 children with rhabdomyosarcoma, treated in a single center between 1972 and 2003, were evaluated to identify those characteristics that may have improved the outcome. Retrospective analysis was performed on 409 children for variables such as age, sex, primary tumor site, TNM (Tumor, Node, Metastasis) stage, Intergroup Rhabdomyosarcoma Studies (IRS) clinical group, histological subtypes, treatment. The mean age was 5.4 years and the male/female ratio was 1.6/1.0. Most of the patients were at stage III and the most common site of metastases was the lung. The median time of follow-up was 114 months. The 10-year event-free survival and overall survival rates were 27% and 33%, respectively. All parameters apart from sex and histological subtypes were found to be correlated with clinical outcome. Orbital and genitourinary system tumors (bladder-prostate tumors excluded), patients >1 year of age, TNM stage I and II tumors, IRS clinical group I and II tumors, grossly resectable tumors, and treatment with chemotherapy protocols containing anthracyclines correlated with better prognoses. In multivariate analyses, tumor invasion to surrounding tissue, regional lymph node involvement, and debulking surgery were found to be negatively correlated with prognosis. In children with rhabdomyosarcoma, survival rates can be improved owing to factors such as advancement in diagnostic and therapeutic techniques, improved supportive care, and a multidisciplinary approach. PMID- 22304008 TI - The mRNA expression of various angiogenesis-related genes in pediatric sarcomas and nonmalignant lesions of tissue. AB - For better understanding cancer pathogenesis and searching a potential target for antineoplastic therapy, the authors have studied mRNA expression profile in tissues from 39 children with histological confirmed malignant sarcomas and from 23 patients with bone and soft tissue nonmalignant lesions. mRNA levels of Angiogenesis-related genes VEGFA (including isoforms of 121, 165, 189), VEGFC, VEGFR-1, VEGFR-2, VEGFR-3, HIF-1alpha, TF, TFPI-1, TFPI-2, uPA, PAI-1 in pediatric specimens were examined using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). uPA, HIF-1alpha, VEGFR-1, VEGFR-2, VEGFR-3, and VEGFC mRNA levels from nonmalignant tissue were significantly higher than those from cancer tissue. On the other hand, isoform VEGFA121 and VEGFA165 and ratio VEGFA165/189 mRNA levels in cancer were higher in comparison with nonmalignant tissue. There was a strong correlation between VEGFA165 and VEGFA189 mRNA expression levels both in cancer tissue and in nonmalignant tissue. In grade 4 tumors in comparison with grade 2 tumors, there was a reduced VEGFA165/189 ratio. Moreover, TFPI-1 and TFPI-2 mRNA levels were significantly lower in sarcomas than in nonmalignant lesions and TFPI-2 was significantly lower in grade 4 tumors than in grade 2. The present data suggested that mRNA overexpression of angiogenesis-related genes is not a prerogative of malignant tissues. The authors supposed that in pediatric bone and soft tissue pathology, high expression of mRNAs of some angiogenesis-related genes may be associated with inflammation and physiological angiogenesis rather than with the development of a malignant tumor. The authors showed the importance of VEGFA121 and/or VEGFA165 and VEGFA165/189 isoform ratio in pediatric sarcomas neoangiogenesis and TFPI-2 for tumors grade 4. PMID- 22304010 TI - Surgical management of Wilms tumor with intravascular extension: a single institution experience. AB - The purpose of this study was to retrospectively analyze the clinical presentation, treatment, and outcomes of children with Wilms tumor (WT) and intravascular extension who were treated at a single institution. A retrospective review was conducted of medical records of all children with Wilms tumor and intravascular extension treated at Virgen del Rocio Children's Hospital between 1992 and 2010. Seven patients (median age 3.4 years, range 2-8.1 years) were identified. At diagnosis, 6 of the 7 patients (85.7%) presented with tumor thrombus that reached the right atrium (RA) and 1 patient with infrahepatic inferior vena cava (IVC) thrombus. All patients received neoadjuvant chemotherapy (SIOP 2001 protocol) with vincristine, doxorubicin, and actinomycin D. Regression of the intravascular extension of the tumor was documented in all patients. Postchemotherapy level of extension was suprahepatic IVC in 1 patient, infrahepatic IVC in 2 patients, renal vein (RV) in 1 patient, and RA in 3 patients. Nephrectomy and thrombectomy were performed in all cases, requiring cardiopulmonary bypass for the 4 patients who presented with suprahepatic IVC and RA thrombus. The other 3 patients with infrahepatic IVC and RV involvement underwent cavotomy and thrombus extraction. Computed tomography, ultrasonography, and echocardiography were used for diagnosis and follow-up. All patients remain disease-free with a median follow-up of 6.3 years (range, 2-19 years). Neoadjuvant chemotherapy for WT with intravascular extension may facilitate the resection by decreasing the extent of the tumor thrombus. Cardiopulmonary bypass is indicated for suprahepatic IVC and RA involvement. Accurate diagnostic imaging is necessary. PMID- 22304011 TI - Potentiation of vincristine toxicity with concomitant fluconazole prophylaxis in children with acute lymphoblastic leukemia. AB - Use of azole antifungals as prophylaxis is becoming an increasingly common practice in acute lymphoblastic leukemia (ALL). Limited literature in adults heightened the awareness of possible increased vincristine (VCR) toxicity in patients receiving concomitant azole therapy. This is due to inhibition of cytochrome P450 3A4, which may increase overall exposure to VCR, resulting in dose reductions or omissions. The primary objective of this study was to determine whether the use of fluconazole prophylaxis increases vincristine toxicity in children with ALL. The authors retrospectively evaluated children with ALL between January 2004 and December 2009. Patients were subdivided into 2 groups based on whether or not they received fluconazole prophylaxis during induction therapy. Data were collected for up to 3 months following the completion of induction therapy. Thirty-one patients were included for analysis. There was no significant difference in gender, race, steroid use, gastrointestinal (GI) toxicity, VCR dose modification, and the rate of fungal or bacterial infections between these 2 groups. Only advanced age is an independent predictor of neuropathy. Patients receiving fluconazole were 4.5 times more likely to experience neuropathy than those not receiving azole; however, this was not statistically significant. The authors report an increased incidence of VCR toxicity in patients with ALL receiving concomitant fluconazole prophylaxis. Judicious use of azole antifungals is warranted in children with ALL. PMID- 22304012 TI - Urinary tract infections in pediatric oncology patients with fever and neutropenia. AB - The relevancy of the urinary tract as a source of infection during febrile neutropenia is not known. The authors sought to determine the frequency of urinary tract infections (UTIs) in pediatric cancer patients with febrile neutropenia. Urine was collected from a mid-stream void before the administration of antibiotics. Demographic, clinical, and laboratory data were collected. The frequency of UTI and usefulness of urinalysis and localizing signs in predicting UTI in pediatric cancer patients with fever and neutropenia were determined. Forty-five patients had 58 febrile neutropenic episodes eligible for study participation. No patient presented with localizing signs. The urinalysis was negative in 53 episodes and positive in 5 episodes. Four patients had 5 UTIs. The frequency of UTI was 8.6% (5 of 58 febrile neutropenia episodes). Four patients had bacteremia, none of whom had a UTI. The sensitivity, specificity, and negative predictive value of urinalysis was 40%, 94%, and 94%, respectively, and for localizing signs was undefined, 100%, and 91%, respectively. UTI is as common as bacteremia in the current pediatric cancer patients with fever and neutropenia. Urinalysis and urine culture should be obtained routinely as part of the diagnostic evaluation of patients with fever and neutropenia. PMID- 22304013 TI - Evaluation of infection control advice for patients at risk of chemotherapy induced neutropenia in 2 pediatric oncology centers: Cape Town, South Africa, and Newcastle-Upon-Tyne, UK. AB - Childhood cancers are treated with myelotoxic chemotherapy. Resultant neutropenia can lead to life-threatening infections. There is no consistent guidance on infection control precautions for neutropenic patients who are not yet febrile or infected. Although it is not possible to eradicate infection risk, it is conceivable that the risk could be reduced by effective infection prevention. This study compared infection control measures advised to pediatric and adolescent oncology patients receiving chemotherapy in 2 centers (Cape Town, South Africa, and Newcastle, UK). Prospective, observational, cross-sectional surveys of staff and patients/parents were undertaken using standardized, study specific questionnaires. Seventy-eight staff and 56 patients/parents participated. Precautions advised in Newcastle were significantly different to Cape Town (all P < .05), except both agreed inpatient isolation was unnecessary. Over 40% of patients/parents felt isolation was important (P < .01). In Cape Town, staff and patients had similar views. In Newcastle, patients/parents had stricter opinions on particular precautions than staff, for example, attending school, playing outside and avoiding busy places (P < .01). Patient/parent responses were similar between centers. Over 90% of staff felt advising patients/parents about hand washing was important. Currently infection prevention advice is inconsistent. Further research is needed to elucidate effective guidance for infection prevention in pediatric neutropenic patients. PMID- 22304014 TI - Liposarcoma in a 5-month-old Chinese girl. PMID- 22304015 TI - Mixed epithelial and stromal tumor of kidney: an exceptional renal neoplasm in an 8-year-old prepubertal girl with isolated clitoral hypertrophy. PMID- 22304016 TI - Early-onset hemophagocytic lymphohistiocytosis after the start of chemotherapy for advanced neuroblastoma. AB - The authors report the clinical course of a 3-year-old boy with stage 4 neuroblastoma (NB) complicated by hemophagocytic lymphohistiocytosis (HLH) immediately after the start of chemotherapy. The NB responded very well to the chemotherapy, but the patient developed high fever on the 2nd day, and was diagnosed as having HLH of the 7th day of chemotherapy. No infections were demonstrated, and massive tumor cell destruction resulting from the rapid effect of chemotherapy was thought to be a cause of systemic cytokine response, resulting in HLH. Methylprednisolone pulse therapy was effective for the HLH, which did not recur thereafter. HLH should be recognized as a serious adverse event during chemotherapy for advanced NB that has a large malignant cell load. PMID- 22304018 TI - Nitrate ion promoted formation of Ag nanowires in polyol processes: a new nanowire growth mechanism. AB - In polyol processes, it was widely accepted that Ag nanowires (NWs) were formed via uniaxial growth of multiple twinned decahedral particles (MTPs) along the {111} facets. Herein, we show that the above MTP uniaxial growth mechanism for growth of nanorods (NRs) and short nanowires (NWs) is different from that for the growth of long Ag NWs. We provide experimental evidence to show that polycrystalline long Ag NWs (up to ~100 MUm) could be formed in high yield (~90%) by a completely different growth mechanism via self-assembly of Ag NPs/NRs. Transmission electron microscope (TEM) measurements show that long Ag NWs are composed of crystalline Ag NPs and NRs with multiple crystal orientations, and many NRs have crystalline structures with pentagonal cross section. Solution phase in situ X-ray diffraction (XRD) measurements show that a strained face centered tetragonal (fct) phase was gradually formed during the formation and growth of long Ag NWs, in addition to the normal face-centered cubic (fcc) phase. The strained fct phase disappears after partial etching by HAuCl(4) and Fe(NO(3))(3). The working conditions for the MTP uniaxial growth mechanism and the current nitrate-promoted self-assembly growth mechanism will be compared and discussed. PMID- 22304019 TI - Sided functions of an arginine-agmatine antiporter oriented in liposomes. AB - The arginine-dependent extreme acid resistance system helps enteric bacteria survive the harsh gastric environment. At the center of this multiprotein system is an arginine-agmatine antiporter, AdiC. To maintain cytoplasmic pH, AdiC imports arginine and exports its decarboxylated product, agmatine, resulting in a net extrusion of one "virtual proton" in each turnover. The random orientation of AdiC in reconstituted liposomes throws up an obstacle to quantifying its transport mechanism. To overcome this problem, we introduced a mutation, S26C, near the substrate-binding site. This mutant exhibits substrate recognition and pH-dependent activity similar to those of the wild-type protein but loses function completely upon reaction with thiol reagents. The membrane-impermeant MTSES reagent can then be used as a cleanly sided inhibitor to silence those S26C AdiC proteins whose extracellular portion projects from the external side of the liposome. Alternatively, the membrane-permeant MTSEA and membrane-impermeant reducing reagent, TCEP, can be used together to inhibit proteins in the opposite orientation. This approach allows steady-state kinetic analysis of AdiC in a sided fashion. Arginine and agmatine have similar Michaelis-Menten parameters for both sides of the protein, while the extracellular side selects arginine over argininamide, a mimic of the carboxylate-protonated form of arginine, more effectively than does the cytoplasmic side. Moreover, the two sides of AdiC have different pH sensitivities. AdiC activity increases to a plateau at pH 4 as the extracellular side is acidified, while the cytoplasmic side shows an optimal pH of 5.5, with further acidification inhibiting transport. This oriented system allows more precise analysis of AdiC-mediated substrate transport than has been previously available and permits comparison to the situation experienced by the bacterial membrane under acid stress. PMID- 22304020 TI - Plasma desmoplakin I biomarker of vascular recurrence after ischemic stroke. AB - Stroke patients have a high risk of vascular recurrence. Biomarkers related to vascular recurrence, however, remain to be identified. The aim of the study was to identify, through proteomic analysis, plasma biomarkers associated with vascular recurrence within one year after the first ischemic stroke. This is a substudy (n = 134) of a large prospective multicenter study of post-stroke patients with an ischemic stroke. Plasma samples were obtained at inclusion. Among the identified proteins, only plasma levels of desmoplakin I were associated with protection against a new vascular event (Odds ratio: 0.64; 95% CI: 0.46-0.89; p = 0.009) after adjustment for hypercholesterolemia, statins and previous atherothrombotic stroke subtype. A greater number of patients without vascular recurrence had been treated with statins within three months of the recent ischemic stroke. Only patients who had been taking statins for 3 months after the ischemic stroke and did not suffer vascular recurrence over a follow-up year, have higher levels of desmoplakin I at the time of inclusion (Odds ratio 0.49; 95% CI: 0.28-0.86; p = 0.013). Increased desmoplakin I levels, determined within 1-3 months of the first ischemic stroke, could be a biomarker for statin responsiveness against a new vascular event in post-ischemic stroke patients taking statins early (1-3 months) after the ischemic stroke. PMID- 22304021 TI - Intra- and interlaboratory reproducibility of ultra performance liquid chromatography-time-of-flight mass spectrometry for urinary metabolic profiling. AB - Liquid chromatography coupled to mass spectrometry (LC-MS) is a major platform in metabolic profiling but has not yet been comprehensively assessed as to its repeatability and reproducibility across multiple spectrometers and laboratories. Here we report results of a large interlaboratory reproducibility study of ultra performance (UP) LC-MS of human urine. A total of 14 stable isotope labeled standard compounds were spiked into a pooled human urine sample, which was subject to a 2- to 16-fold dilution series and run by UPLC coupled to time-of flight MS at three different laboratories all using the same platform. In each lab, identical samples were run in two phases, separated by at least 1 week, to assess between-day reproducibility. Overall, platform reproducibility was good with median mass accuracies below 12 ppm, median retention time drifts of less than 0.73 s and coefficients of variation of intensity of less than 18% across laboratories and ionization modes. We found that the intensity response was highly linear within each run, with a median R(2) of 0.95 and 0.93 in positive and negative ionization modes. Between-day reproducibility was also high with a mean R(2) of 0.93 for a linear relationship between the intensities of ions recorded in the two phases across the laboratories and modes. Most importantly, between-lab reproducibility was excellent with median R(2) values of 0.96 and 0.98 for positive and negative ionization modes, respectively, across all pairs of laboratories. Interestingly, the three laboratories observed different amounts of adduct formation, but this did not appear to be related to reproducibility observed in each laboratory. These studies show that UPLC-MS is fit for the purpose of targeted urinary metabolite analysis but that care must be taken to optimize laboratory systems for quantitative detection due to variable adduct formation over many compound classes. PMID- 22304022 TI - Translating the role of vitamin D3 in infectious diseases. AB - Vitamin D(3) affects both the innate as well as adaptive immune responses. Epidemiological studies have established that vitamin D(3) deficiency plays an important role in tuberculosis (TB) and viral influenza prevalence as well as susceptibility to active disease in TB. Vitamin D(3) status has been associated with the clinical course of HIV infection and drug interaction with anti retroviral therapy. This article reviews the immunomodulatory capacity of vitamin D(3) and examines the impact of vitamin D(3) supplementation as a preventive or therapeutic intervention with the intent to uncover its potential therapeutic application in infectious diseases and to identify novel areas for future research. We present a review of randomized, controlled clinical studies conducted in humans which included assessment of the immune function or clinical outcome as study end points. Current data support vitamin D(3) supplementation as risk-modifying intervention in tuberculosis and viral respiratory tract infection, but the optimal dosage regimen remains to be determined. However, to date the knowledge on its role in fungal infection and sepsis is limited although a potential benefit could be harnessed from its ability to curtail the unrestrained pro-inflammatory response and therefore prevent excessive collateral tissue damage. PMID- 22304023 TI - Ophthalmic research in Australasia. PMID- 22304024 TI - Intravitreous bevacizumab adult safety data: the evidence so far. PMID- 22304025 TI - Therapeutic targeting of the complement system in age-related macular degeneration: a review. AB - The last decade has produced pivotal change in our understanding of the molecular mechanisms underlying age-related macular degeneration (AMD), a leading cause of global blindness. In this time, the complement system has featured as a unifying theme for several elements of new evidence: initially, the discovery of complement proteins within drusen and subsequently, the association between AMD and mutations in various complement pathway genes, most notably complement factor H. Increasingly, a wealth of data are pointing towards a role for chronic local inflammation and complement activation in the patho-aetiology of AMD. These findings have paved the way for the exploration of a new paradigm of therapy in AMD management; targeting of specific molecular constituents in the complement pathway thus producing dampening or inhibition of the inflammatory response. Such an approach has the potential to intervene earlier in the disease process and ideally before vision is compromised. In this review we discuss the role of the complement system in AMD, novel therapies in preclinical evaluation and clinical trial, and whether these have a part to play in reducing the burden of disease. PMID- 22304027 TI - Transient-state fluctuationlike relation for the driving force on a biomolecule. AB - In experiments and simulations the force acting on a single biomolecular system has been observed as a fluctuating quantity if the system is driven under constant velocity. We ask the question that is analogous to transient state entropy production and work fluctuation relations whether the force fluctuations observed in the single biomolecular system satisfy a transient state fluctuationlike relation, and the answer is in the affirmative. Using a constant velocity pulling steered molecular dynamics simulation study for protein unfolding, we confirm that the force fluctuations of this single biomolecular system satisfy a transient-state fluctuationlike relation 1/gamma(T,v) ln[P(v)(+f)/P(v)(-f)] = f. P(v)(+/-f) is the probability of positive and negative values of forces f = f . for a given unfolding velocity of magnitude v and the pulling direction n, nis the unit vector of n, and gamma(T,v) is a factor that depends on initial equilibrium temperature T and the unfolding velocity. For different unfolding velocities we find that the system in the nonequilibrium pulling region displays substantial negative fluctuation in its unfolding force when velocity decreases. A negative value of force may indicate the emergence of refolding behavior during protein unfolding. We also find that gamma(T,v) ~ T( delta)v(alpha) and the system relaxation time tau(T,v) ~ T(delta)v(-(1+alpha), where alpha and delta are scaling exponents. PMID- 22304028 TI - Computation as an emergent feature of adaptive synchronization. AB - We report on the spontaneous emergence of computation from adaptive synchronization of networked dynamical systems. The fundamentals are nonlinear elements, interacting in a directed graph via a coupling that adapts itself to the synchronization level between two input signals. These units can emulate different Boolean logics, and perform any computational task in a Turing sense, each specific operation being associated with a given network's motif. The resilience of the computation against noise is proven, and the general applicability is demonstrated with regard to periodic and chaotic oscillators, and excitable systems mimicking neural dynamics. PMID- 22304029 TI - Nonmonotonic settling of a sphere in a cornstarch suspension. AB - Cornstarch suspensions exhibit remarkable behavior. Here, we present two unexpected observations for a sphere settling in such a suspension: In the bulk of the liquid the velocity of the sphere oscillates around a terminal value, without damping. Near the bottom the sphere comes to a full stop, but then accelerates again toward a second stop. This stop-go cycle is repeated several times before the object reaches the bottom. We show that common shear thickening or linear viscoelastic models cannot account for the observed phenomena, and propose a minimal jamming model to describe the behavior at the bottom. PMID- 22304030 TI - Bulk and shear moduli of compressed microgel suspensions. AB - We independently determine the bulk and shear moduli of compressed microgel suspensions and the bulk modulus of individual microgel particles and find that the elastic behavior of the suspension reflects the degree of compression of the particles. This feature, which is distinct from other soft materials such as emulsions or foams, can give rise to an unusually large difference between the bulk and shear moduli of the suspension. Our results extend our understanding of soft materials to systems based on compressible objects, opening up possibilities for engineering materials with drastically different responses to shear and compression. PMID- 22304031 TI - Short-range correlations seen in the nematic phase of bent-core liquid crystals by dielectric and electro-optic studies. AB - Three bent-core nematic liquid crystals having the same core but with different terminal groups, short (C4) and long (C7,C9) tails, are investigated by dielectric and electro-optic contrast spectroscopic techniques. C4 shows sign reversal in the dielectric anisotropy Deltaepsilon' as a function of both temperature and frequency, whereas C9 shows only negative Deltaepsilon' in the entire mesophasic region. The behavior of C7 is intermediate of the two. Results of a dielectric study show that both C7 and C9 exhibit strong short-range polar correlations normal to the director. The correlation lengths of these interactions are found to be similar to those from the x-ray scattering. An increased hindered rotation for C9 compared to C4 moves the dielectric dispersion for epsilon(|') to much lower frequencies, such that C9 shows only negative Deltaepsilon' over the entire temperature range. PMID- 22304032 TI - Electronic properties of conductive pili of the metal-reducing bacterium Geobacter sulfurreducens probed by scanning tunneling microscopy. AB - The metal-reducing bacterium Geobacter sulfurreducens produces conductive protein appendages known as "pilus nanowires" to transfer electrons to metal oxides and to other cells. These processes can be harnessed for the bioremediation of toxic metals and the generation of electricity in bioelectrochemical cells. Key to these applications is a detailed understanding of how these nanostructures conduct electrons. However, to the best of our knowledge, their mechanism of electron transport is not known. We used the capability of scanning tunneling microscopy (STM) to probe conductive materials with higher spatial resolution than other scanning probe methods to gain insights into the transversal electronic behavior of native, cell-anchored pili. Despite the presence of insulating cellular components, the STM topography resolved electronic molecular substructures with periodicities similar to those reported for the pilus shaft. STM spectroscopy revealed electronic states near the Fermi level, consistent with a conducting material, but did not reveal electronic states expected for cytochromes. Furthermore, the transversal conductance was asymmetric, as previously reported for assemblies of helical peptides. Our results thus indicate that the Geobacter pilus shaft has an intrinsic electronic structure that could play a role in charge transport. PMID- 22304033 TI - Boundary-induced orientation of dynamic filament networks and vesicle agglomerations. AB - We find a statistical mechanism that can adjust orientations of intracellular filaments to cell geometry in the absence of organizing centers. The effect is based on random and isotropic filament (de-)polymerization dynamics and is independent of filament interactions and explicit regulation. It can be understood by an analogy to electrostatics and appears to be induced by the confining boundaries; for periodic boundary conditions, no orientational bias emerges. Including active transport of particles, the model reproduces experimental observations of vesicle accumulations in transected axons. PMID- 22304034 TI - Order statistics of 1/falpha signals. AB - Order statistics of periodic, Gaussian noise with 1/f(alpha) power spectrum is investigated. Using simulations and phenomenological arguments, we find three scaling regimes for the average gap d(k) = (x(k) -x(k) + 1) between the kth and (k+1)st largest values of the signal. The result d(k) k(-1), known for independent, identically distributed variables, remains valid for 0 <= alpha < 1. Nontrivial, alpha-dependent scaling exponents, d(k) k((alpha-3)/2), emerge for 1 < alpha < 5, and, finally, alpha-independent scaling, d(k) ~ k, is obtained for alpha > 5. The spectra of average ordered values epsilon(k) =(x(1) - x(k))~ k(beta) is also examined. The exponent beta is derived from the gap scaling as well as by relating epsilon(k) to the density of near-extreme states. Known results for the density of near-extreme states combined with scaling suggest that beta(alpha = 2) = 1/2, beta(4) = 3/2, and beta(infinity) = 2 are exact values. We also show that parallels can be drawn between epsilon(k) and the quantum mechanical spectra of a particle in power-law potentials. PMID- 22304035 TI - Ground states of the lattice-gas model on the triangular lattice with nearest- and next-nearest-neighbor pairwise interactions and with three-particle interaction: ground states at boundaries of full-dimensional regions. AB - We analyze the ground states at boundaries of four-dimensional (full-dimensional) ground-state regions of the lattice-gas model on the infinite plane triangular lattice with nearest- and next-nearest-neighbor pairwise interactions and with additional interaction between three particles at the vertices of a nearest neighbor triangle. In such a way we determine the ground states at fixed density of particles (coverage) and make the comparison to experiments possible. A surprisingly rich variety of structures is found: ordered periodic, ordered-but aperiodic, disordered with various degree of disorder, and multiple-twin structures. The first-order and continuous phase transitions are identified. The degree of disorder for disordered ground states is analyzed. One of the most interesting results is the discovery of an infinite sequence of ground states at a boundary between two phases. PMID- 22304036 TI - Avalanche spatial structure and multivariable scaling functions: sizes, heights, widths, and views through windows. AB - We introduce a systematic method for extracting multivariable universal scaling functions and critical exponents from data. We exemplify our insights by analyzing simulations of avalanches in an interface using simulations from a driven quenched Kardar-Parisi-Zhang (qKPZ) equation. We fully characterize the spatial structure of these avalanches--we report universal scaling functions for size, height, and width distributions, and also local front heights. Furthermore, we resolve a problem that arises in many imaging experiments of crackling noise and avalanche dynamics, where the observed distributions are strongly distorted by a limited field of view. Through artificially windowed data, we show these distributions and their multivariable scaling functions may be written in terms of two control parameters: the window size and the characteristic length scale of the dynamics. For the entire system and the windowed distributions we develop accurate parametrizations for the universal scaling functions, including corrections to scaling and systematic error bars, facilitated by a novel software environment SloppyScaling. PMID- 22304037 TI - Fractional Feynman-Kac equation for weak ergodicity breaking. AB - The continuous-time random walk (CTRW) is a model of anomalous subdiffusion in which particles are immobilized for random times between successive jumps. A power-law distribution of the waiting times, psi(tau) ~ tau(-(1+alpha)), leads to subdiffusion (x(2) ~ t(alpha)) for 0 < alpha < 1. In closed systems, the long stagnation periods cause time averages to divert from the corresponding ensemble averages, which is a manifestation of weak ergodicity breaking. The time average of a general observable U(t) = 1/t ?(0)(t) U[x(tau)]dtau is a functional of the path and is described by the well-known Feynman-Kac equation if the motion is Brownian. Here, we derive forward and backward fractional Feynman-Kac equations for functionals of CTRW in a binding potential. We use our equations to study two specific time averages: the fraction of time spent by a particle in half-box, and the time average of the particle's position in a harmonic field. In both cases, we obtain the probability density function of the time averages for t -> infinity and the first two moments. Our results show that both the occupation fraction and the time-averaged position are random variables even for long times, except for alpha = 1, when they are identical to their ensemble averages. Using our fractional Feynman-Kac equation, we also study the dynamics leading to weak ergodicity breaking, namely the convergence of the fluctuations to their asymptotic values. PMID- 22304038 TI - Casimir force induced by an imperfect Bose gas. AB - We present a study of the Casimir effect in an imperfect (mean-field) Bose gas contained between two infinite parallel plane walls. The derivation of the Casimir force follows from the calculation of the excess grand-canonical free energy density under periodic, Dirichlet, and Neumann boundary conditions with the use of the steepest descent method. In the one-phase region, the force decays exponentially fast when distance D between the walls tends to infinity. When the Bose-Einstein condensation point is approached, the decay length in the exponential law diverges with critical exponent nu(IMP) = 1, which differs from the perfect gas case where nu(P) = 1/2. In the two-phase region, the Casimir force is long range and decays following the power law D(-3), with the same amplitude as in the perfect gas. PMID- 22304039 TI - Nonequilibrium steady state of a stochastic system driven by a nonlinear drift force. AB - We investigate the properties of the nonequilibrium steady state for the stochastic system driven by a nonlinear drift force and influenced by noises that are not identically and independently distributed. The nonequilibrium steady state (NESS) current results from a residual part of the drift force that is not canceled by the diffusive action of noises. From our previous study for the linear drift force, the NESS current was found to circulate on the equiprobability surface with the maximum at a stable fixed point of the drift force. For the nonlinear drift force, we use the perturbation theory with respect to the cubic and quartic coefficients of the drift force. We find an interesting potential landscape picture where the probability maximum shifts from the fixed point of the drift force and, furthermore, the NESS current has a nontrivial circulation that flows off the equiprobability surface and has various centers not located at the probability maximum. The theoretical result is well confirmed by the computer simulation. PMID- 22304040 TI - Evaporation-condensation transition of the two-dimensional Potts model in the microcanonical ensemble. AB - The evaporation-condensation transition of the Potts model on a square lattice is numerically investigated by the Wang-Landau sampling method. An intrinsically system-size-dependent discrete transition between supersaturation state and phase separation state is observed in the microcanonical ensemble by changing constrained internal energy. We calculate the microcanonical temperature, as a derivative of microcanonical entropy, and condensation ratio, and perform a finite-size scaling of them to indicate the clear tendency of numerical data to converge to the infinite-size limit predicted by phenomenological theory for the isotherm lattice gas model. PMID- 22304041 TI - Negative thermal conductivity of chains of rotors with mechanical forcing. AB - We consider chains of rotors subjected to both thermal and mechanical forcings in a nonequilibrium steady state. Unusual nonlinear profiles of temperature and velocities are observed in the system. In particular, the temperature is maximal in the center, which is an indication of the nonlocal behavior of the system. Despite this uncommon behavior, local equilibrium holds for long enough chains. Our numerical results also show that when the mechanical forcing is strong enough, the energy current can be increased by an inverse temperature gradient. This counterintuitive result again reveals the complexity of nonequilibrium states. PMID- 22304042 TI - Reliable index for measuring information flow. AB - The estimation of causal relationships from time series data is an important factor in predicting or regulating control in various fields. Usually, when estimating causal relationships, either a causality or a correlation measure is used. However, many studies fail to adequately consider qualitative differences and relations between these measures when applied to time series. In this paper, we present a unified formulation of the causality measure based on information theory as well as relationships and disparities between correlation and causality measures. An advantage of our approach is that the formulated causality measure can extract linear subspaces with strong causal relationships. A significant contribution is the verification that time-delayed mutual information (TDMI) is not appropriate for nonindependent and identically distributed (non-i.i.d.) time series, which is done by demonstrating the behavior of projection vectors in an experiment with synthetic data. PMID- 22304043 TI - Thermodynamic cost of measurements. AB - The measurement of thermal fluctuations provides information about the microscopic state of a thermodynamic system and can be used in order to extract work from a single heat bath in a suitable cyclic process. We present a minimal framework for the modeling of a measurement device and we propose a protocol for the measurement of thermal fluctuations. In this framework, the measurement of thermal fluctuations naturally leads to the dissipation of work. We illustrate this framework on a simple two states system inspired by the Szilard's information engine. PMID- 22304044 TI - Non-Gaussian stochastic dynamics of spins and oscillators: a continuous-time random walk approach. AB - We consider separately a spin and an oscillator that are coupled to their environment. After a finite interval of random length, the state of the environment changes, and each change causes a random change in the resonance frequency of the spin or vibrational frequency of the oscillator. Mathematically, the evolution of these frequencies is described by a continuous-time random walk. Physically, the stochastic dynamics can be understood as non-Gaussian because the frequency of the system and state of the environment change on comparable time scales. These dynamics are also nonstationary, and so might apply to a nonequilibrium environment. The resonance and vibrational spectra of the spin and oscillator, as well as the ensemble-averaged displacement of the oscillator, are investigated in detail. We observe some distinct non-Gaussian features of the dynamics, such as the narrow, leptokurtic shape of the resonance spectrum of the spin and beating of the average oscillator displacement. The convergence to Gaussian dynamics as changes in the environment occur with increasing frequency is also considered. Among other results, we observe narrowing of the resonance and vibrational lines in the Gaussian limit due to a weakening of the system environment interaction. PMID- 22304045 TI - Jarzynski equality in van der Pol and Rayleigh oscillators. AB - We have studied the Jarzynski equality (JE) in van der Pol and Rayleigh oscillators, which are typical deterministic non-Hamiltonian models but not expected to rigorously satisfy the JE because they are not reversible. Our simulations that calculate the contribution to the work W of an applied ramp force with a duration tau show that the JE approximately holds for a fairly wide range of tau including tau -> 0 and tau -> infinity, except for tau ~ T, where T denotes the period of relaxation oscillations in the limit cycle. The work distribution function (WDF) is shown to be non-Gaussian with the U-shaped structure for a strong damping parameter. The tau dependence of R ( = k(B)(Tln(e)(-betaW)) obtained by our simulations is semiquantitatively elucidated with the use of a simple expression for limit-cycle oscillations, where the bracket (.) expresses an average over the WDF. The result obtained in self excited oscillators is in contrast with the fact that the JE holds in the Nose Hoover oscillator, which also belongs to deterministic non-Hamiltonian models. PMID- 22304046 TI - Thermodynamic formula for the cumulant generating function of time-averaged current. AB - The cumulant generating function of time-averaged current is studied from an operational viewpoint. Specifically, for interacting Brownian particles under nonequilibrium conditions, we show that the first derivative of the cumulant generating function is equal to the expectation value of the current in a modified system with an extra force added, where the modified system is characterized by a variational principle. The formula reminds us of Einstein's fluctuation theory in equilibrium statistical mechanics. Furthermore, since the formula leads to the fluctuation-dissipation relation when the linear response regime is focused on, it is regarded as an extension of the linear response theory to that valid beyond the linear response regime. The formula is also related to previously known theories such as the Donsker-Varadhan theory, the additivity principle, and the least dissipation principle, but it is not derived from them. Examples of its application are presented for a driven Brownian particle on a ring subject to a periodic potential. PMID- 22304047 TI - Superdiffusion induced by a long-correlated external random force. AB - We consider a particle immersed in a thermal reservoir and simultaneously subjected to an external random force that drives the system to a nonequilibrium situation. Starting from a Langevin equation description, we derive exact expressions for the mean-square displacement and the velocity autocorrelation function of the diffusing particle. An effective temperature is introduced to characterize the deviation from the internal equilibrium situation. Using a power law force autocorrelation function, the mean-square displacement and the velocity autocorrelation function are analytically obtained in terms of Mittag-Leffler functions. In this case, we show that the present model exhibits a superdiffusive regime as a consequence of the competition between passive and active processes. PMID- 22304048 TI - Statistical description of Coulomb-like systems. AB - The solution of the problem of the partition function calculation for a Coulomb like system is proposed. The quantum-field-theory approach is used to give a statistical description of a system of interacting particles with due regard to arbitrary spatially inhomogeneous configurations. Formation of structures in a Coulomb-like system is analyzed and applied to the case of of dusty crystals and two-dimensional colloidal crystals. In the one-dimensional case, an exact solution for the spatial distribution of charged particles is obtained. In the two- dimensional case, the exact partition function for homogeneous distribution of particles is presented. We have analytically derived the necessary condition for the crystal formation in a system of interacting particles in the three dimensional case. PMID- 22304049 TI - Perturbation calculation of thermodynamic density of states. AB - The density of states g (epsilon) is frequently used to calculate the temperature dependent properties of a thermodynamic system. Here a derivation is given for calculating the warped density of states g*(epsilon) resulting from the addition of a perturbation. The method is validated for a classical Heisenberg model of bcc Fe and the errors in the free energy are shown to be second order in the perturbation. Taking the perturbation to be the difference between a first principles quantum-mechanical energy and a corresponding classical energy, this method can significantly reduce the computational effort required to calculate g(epsilon) for quantum systems using the Wang-Landau approach. PMID- 22304050 TI - Maxwell's demon and data compression. AB - In an asymmetric Szilard engine model of Maxwell's demon, we show the equivalence between information theoretical and thermodynamic entropies when the demon erases information optimally. The work gain by the engine can be exactly canceled out by the work necessary to reset the demon's memory after optimal data compression in the manner of Shannon before the erasure. PMID- 22304051 TI - Fluctuation relations with intermittent non-Gaussian variables. AB - Nonequilibrium stationary fluctuations may exhibit a special symmetry called fluctuation relations (FRs). Here, we show that this property is always satisfied by the subtraction of two random and independent variables related by a thermodynamiclike change of measure. Taking one of them as a modulated Poisson process, it is demonstrated that intermittence and FRs are compatible properties that may coexist naturally. Strong non-Gaussian features characterize the probability distribution and its generating function. Their associated large deviation functions develop a "kink" at the origin and a plateau regime respectively. Application of this model in different stationary nonequilibrium situations is discussed. PMID- 22304052 TI - Design of two-tooth unidirectional rotary-ratchet molecular machines driven by linearly polarized ac fields. AB - An artificial molecular rotor system mounted in a biological membrane, which can unidirectionally rotate in response to weak pumping from a linearly polarized ac field, is modeled. The dynamics of the rotor unit are described by the Langevin equation for a particle in a two-dimensional bistable potential with a two-tooth ratchet structure. This model reveals effects due to the two-dimensionality of the ratchet and the polarization of the applied field. First, we demonstrate that a unidirectional rotation appears with stochastic resonance exhibiting a bell shaped peak for noise intensity in the mean angular momentum (MAM) of the rotor. An analytical expression for the MAM, (L), is obtained on the basis of a four state Markov approximation. Second, a significant effect due to torsional nonlinearity (representing the ratchet-like structure) in the potential geometry is quantified: in the absence of torsion, the MAM depends on the polarization angle phi of the applied field as (L) sin(2phi), whereas in the presence of torsion, an additional bias appears in the MAM as (L)(bias + sin(2phi)). It is found that this effect can be used to make the rotor system robustly maintain rotation in a single direction independent of the mounting conditions. Possible designs for an artificial molecular rotor system using the torsion effect are discussed. PMID- 22304053 TI - Brownian motion in shear flow: direct observation of anomalous diffusion. AB - Brownian motion in a simple shear flow has been experimentally investigated by using a different method for observation and analysis. A number of polystyrene spheres dispersed in sheared water were tracked with a confocal scanning laser microscope, and the time dependences of their coordinates were obtained. Since in the usual mean-square displacement in the flow direction the contribution from the Brownian motion is overwhelmed by that due to the convection, we considered an alternative displacement for which the convection effect could be removed. We found that the new mean-square displacement consists of the normal Einstein diffusion term, which is linear in t, and an anomalous t(3) term arising from the coupling between the diffusion along the velocity gradient and the convection. PMID- 22304054 TI - Signal-to-noise ratio in parametrically driven oscillators. AB - We report a theoretical model based on Green's functions and averaging techniques that gives analytical estimates to the signal-to-noise ratio (SNR) near the first parametric instability zone in parametrically driven oscillators in the presence of added ac drive and added thermal noise. The signal term is given by the response of the parametrically driven oscillator to the added ac drive, while the noise term has two different measures: one is dc and the other is ac. The dc measure of noise is given by a time average of the statistically averaged fluctuations of the displacement from equilibrium in the parametric oscillator due to thermal noise. The ac measure of noise is given by the amplitude of the statistically averaged fluctuations at the frequency of the parametric pump. We observe a strong dependence of the SNR on the phase between the external drive and the parametric pump. For some range of the phase there is a high SNR, while for other values of phase the SNR remains flat or decreases with increasing pump amplitude. Very good agreement between analytical estimates and numerical results is achieved. PMID- 22304055 TI - Molecular dynamics simulations of weak detonations. AB - Detonation of a three-dimensional reactive nonisotropic molecular crystal is modeled using molecular dynamics simulations. The detonation process is initiated by an impulse, followed by the creation of a stable fast reactive shock wave. The terminal shock velocity is independent of the initiation conditions. Further analysis shows supersonic propagation decoupled from the dynamics of the decomposed material left behind the shock front. The dependence of the shock velocity on crystal nonlinear compressibility resembles solitary behavior. These properties categorize the phenomena as a weak detonation. The dependence of the detonation wave on microscopic potential parameters was investigated. An increase in detonation velocity with the reaction exothermicity reaching a saturation value is observed. In all other respects the model crystal exhibits typical properties of a molecular crystal. PMID- 22304056 TI - Model-free thermodynamics of fluid vesicles. AB - Motivated by a long-standing debate concerning the nature and interrelations of surface-tension variables in fluid membranes, we reformulate the thermodynamics of a membrane vesicle as a generic two-dimensional finite system enclosing a three-dimensional volume. The formulation is shown to require two tension variables, conjugate to the intensive constraints of area per molecule and volume to-area ratio. We obtain the relation between these two variables in various scenarios, as well as their correspondence to other definitions of tension variables for membranes. Several controversies related to membrane tension are thereby resolved on a model-free thermodynamic level. The thermodynamic formulation may be useful also for treating large-scale properties of vesicles that are insensitive to the membrane's detailed statistical mechanics and interactions. PMID- 22304057 TI - Stochastic dynamics beyond the weak coupling limit: thermalization. AB - We discuss the structure and asymptotic long-time properties of coupled equations for the moments of a Brownian particle's momentum p(n)((t)) derived microscopically beyond the lowest approximation in the weak coupling parameter lambda. Generalized fluctuation-dissipation relations are derived and shown to ensure convergence to thermal equilibrium to any order in lambda. PMID- 22304058 TI - Multiplication law and S transform for non-Hermitian random matrices. AB - We derive a multiplication law for free non-Hermitian random matrices allowing for an easy reconstruction of the two-dimensional eigenvalue distribution of the product ensemble from the characteristics of the individual ensembles. We define the corresponding non-Hermitian S transform being a natural generalization of the Voiculescu S transform. In addition, we extend the classical Hermitian S transform approach to deal with the situation when the random matrix ensemble factors have vanishing mean including the case when both of them are centered. We use planar diagrammatic techniques to derive these results. PMID- 22304059 TI - Stability intervals of metastable states in hysteretic systems. AB - Hysteresis in disordered systems originates in a plethora of metastable states. Previous works focused on their distribution inside the hysteresis. In contrast, an analysis of their range of metastability is proposed. This model, designed to catch the main features of fluid adsorption in porous materials, shows strong evidence that, in the thermodynamic limit, despite that metastable states of finite range can be found, they are exponentially dominated by those infinitely localized states. PMID- 22304060 TI - Orbital ice: an exact Coulomb phase on the diamond lattice. AB - We demonstrate the existence of an orbital Coulomb phase as the exact ground state of a p-orbital exchange Hamiltonian on the diamond lattice. The Coulomb phase is an emergent state characterized by algebraic dipolar correlations and a gauge structure resulting from local constraints (ice rules) of the underlying lattice models. For most ice models on the pyrochlore lattice, these local constraints are a direct consequence of minimizing the energy of each individual tetrahedron. On the contrary, the orbital ice rules are emergent phenomena resulting from the quantum orbital dynamics. We show that the orbital ice model exhibits an emergent geometrical frustration by mapping the degenerate quantum orbital ground states to the spin-ice states obeying the 2-in-2-out constraints on the pyrochlore lattice. We also discuss possible realization of the orbital ice model in optical lattices with p-band fermionic cold atoms. PMID- 22304061 TI - Nonperturbative renormalization group for the Kardar-Parisi-Zhang equation: general framework and first applications. AB - We present an analytical method, rooted in the nonperturbative renormalization group, that allows one to calculate the critical exponents and the correlation and response functions of the Kardar-Parisi-Zhang (KPZ) growth equation in all its different regimes, including the strong-coupling one. We analyze the symmetries of the KPZ problem and derive an approximation scheme that satisfies the linearly realized ones. We implement this scheme at the minimal order in the response field, and show that it yields a complete, qualitatively correct phase diagram in all dimensions, with reasonable values for the critical exponents in physical dimensions. We also compute in one dimension the full (momentum and frequency dependent) correlation function, and the associated universal scaling function. We find a very satisfactory quantitative agreement with the exact result from Prahofer and Spohn [J. Stat. Phys. 115, 255 (2004)]. In particular, we obtain for the universal amplitude ratio g_{0}?1.149(18), to be compared with the exact value g_{0}=1.1504... (the Baik and Rain [J. Stat. Phys. 100, 523 (2000)] constant). We emphasize that all these results, which can be systematically improved, are obtained with sole input the bare action and its symmetries, without further assumptions on the existence of scaling or on the form of the scaling function. PMID- 22304062 TI - Space fractional Wigner equation and its semiclassical limit. AB - Manifestations of space fractional quantum mechanics (SFQM), as it was formulated by Laskin [Phys. Rev. E 62, 3135 (2000)], are deemed to offer a better physical interpretation of Levy flight statistics on a quantum mechanical level. We start with the SFQM Schrodinger equation characterized by a Levy flight index alpha? (1,2), perform a Wigner transform, and draw the limit h/Etau -> 0 (i.e., let the observed energy scale E go to infinity in comparison to the quantization given by h/tau). In order to obtain classical transport equations two possible substitutions for the terms |p|(alpha) and |p'|alpha which appear in von Neumann's equation are presented. It is demonstrated that they conform to the criteria for a successful Wigner transform. Their benefits and caveats are discussed in detail. We find, that, indeed, SFQM manifests itself in an anomalous kinetic term of the free particle's motion and, assuming an external potential diagonal in momentum space for the sake of simplicity, in corresponding anomalous terms in the resulting drift current. All our results reduce to the classical forms in the limit alpha = 2. PMID- 22304063 TI - Collision statistics for random flights with anisotropic scattering and absorption. AB - For a broad class of random walks with anisotropic scattering kernels and absorption, we derive explicit formulas that allow expressing the moments of the collision number n(V) performed in a volume V as a function of the particle equilibrium distribution. Our results apply to arbitrary domains V and boundary conditions, and allow assessing the hitting statistics for systems where the typical displacements are comparable to the domain size, so that the diffusion limit is possibly not attained. An example is discussed for one-dimensional random flights with exponential displacements, where analytical calculations can be carried out. PMID- 22304064 TI - Non-Markovian models for migration-proliferation dichotomy of cancer cells: anomalous switching and spreading rate. AB - Proliferation and migration dichotomy of the tumor cell invasion is examined within two non-Markovian models. We consider the tumor spheroid, which consists of the tumor core with a high density of cells and the outer invasive zone. We distinguish two different regions of the outer invasive zone and develop models for both zones. In model I we analyze the near-core-outer region, where biased migration away from the tumor spheroid core takes place. We suggest non-Markovian switching between the migrating and proliferating phenotypes of tumor cells. Nonlinear master equations for mean densities of cancer cells of both phenotypes are derived. In anomalous switching case we estimate the average size of the near core-outer region that corresponds to sublinear growth (r(t)) ~ t(MU) for 0 < MU < 1. In model II we consider the outer zone, where the density of cancer cells is very low. We suggest an integrodifferential equation for the total density of cancer cells. For proliferation rate we use the classical logistic growth, while the migration of cells is subdiffusive. The exact formulas for the overall spreading rate of cancer cells are obtained by a hyperbolic scaling and Hamilton Jacobi techniques. PMID- 22304065 TI - Langevin dynamics, entropic crowding, and stochastic cloaking. AB - We consider a pack of independent probes--within a spatially inhomogeneous thermal bath consisting of a vast number of randomly moving particles--which are subjected to an external force. The stochastic dynamics of the probes are governed by Langevin's equation. The probes attain a steady state distribution which, in general, is different than the concentration of the particles in the spatially inhomogeneous thermal bath. In this paper we explore the state of "entropic crowding" in which the probes' distribution and the particles' concentration coincide--thus yielding maximal relative entropies of one with respect to the other. Entropic crowding can be attained by two scenarios which are analyzed in detail: (i) "entropically crowding thermal baths"--in which the particles crowd uniformly around the probes; (ii) "entropically crowding Langevin forces"--in which the probes crowd uniformly amongst the particles. Entropic crowding is equivalent to the optimal stochastic cloaking of the probes within the spatially inhomogeneous thermal bath. PMID- 22304066 TI - Parametric correlations versus fidelity decay: the symmetry breaking case. AB - We provide formulas for fidelity decay and parametric energy correlations for random matrix ensembles where time-reversal invariance of the original Hamiltonian is broken by the perturbation. Like in the case of a symmetry conserving perturbation a simple relation between both quantities exists. Fidelity freeze is observed for systems with even and odd spin. PMID- 22304067 TI - Entrainment of a driven oscillator as a dynamical phase transition. AB - Large deviation theory has emerged as the natural language with which to study transitions between dynamical phases, such as the glass transition. Here we use this approach to show that the entrainment of an oscillator to an external driving force can be described as a phase transition between two regions in a joint space-time representation. Specifically, we numerically obtain exact solutions of the large deviation function for a discrete, finite model of an oscillator under a periodically varying external force. We find that the first derivative of the expectation value of the current diverges in the limit of large system size. For weak forcing, perturbation theory allows us to relate the observed frequency of the oscillator to the spectrum of eigenvalues for the unforced system. We find that in the entrainment region where the oscillator exhibits the frequency of the driving force, there is a strong coupling between the ground state and excited states. PMID- 22304068 TI - Ingredients of thermal rectification: the case of classical and quantum self consistent harmonic chains of oscillators. AB - In order to identify the ingredients of thermal rectification, we analytically investigate the heat flow in the asymmetric classical and quantum self-consistent harmonic chains of oscillators. We confirm the absence of rectification in the classical version of the model, and, for the quantum analog, we show that the combination of a local heat flow proportional to the temperature gradient and a local thermal conductivity dependent on parameters asymmetrically distributed in the chain and on the local temperature lead to thermal rectification. Some of these ingredients are provided by the quantum nature of the specific model analyzed here, but they are not restricted to quantum phenomena and can also appear in anharmonic classical models. The comprehension of such mechanism is important for the advance of phononics, since thermal rectifiers are the basic components of several devices proposed to control the heat flow. PMID- 22304069 TI - Depletion potentials in highly size-asymmetric binary hard-sphere mixtures: comparison of simulation results with theory. AB - We report a detailed study, using state-of-the-art simulation and theoretical methods, of the effective (depletion) potential between a pair of big hard spheres immersed in a reservoir of much smaller hard spheres, the size disparity being measured by the ratio of diameters q = sigma(s)/sigma(b). Small particles are treated grand canonically, their influence being parameterized in terms of their packing fraction in the reservoir eta(s)(r). Two Monte Carlo simulation schemes--the geometrical cluster algorithm, and staged particle insertion--are deployed to obtain accurate depletion potentials for a number of combinations of q <= 0.1 and eta(s)(r). After applying corrections for simulation finite-size effects, the depletion potentials are compared with the prediction of new density functional theory (DFT) calculations based on the insertion trick using the Rosenfeld functional and several subsequent modifications. While agreement between the DFT and simulation is generally good, significant discrepancies are evident at the largest reservoir packing fraction accessible to our simulation methods, namely, eta(s)(r) = 0.35. These discrepancies are, however, small compared to those between simulation and the much poorer predictions of the Derjaguin approximation at this eta(s)(r). The recently proposed morphometric approximation performs better than Derjaguin but is somewhat poorer than DFT for the size ratios and small-sphere packing fractions that we consider. The effective potentials from simulation, DFT, and the morphometric approximation were used to compute the second virial coefficient B(2) as a function of eta(s)(r). Comparison of the results enables an assessment of the extent to which DFT can be expected to correctly predict the propensity toward fluid-fluid phase separation in additive binary hard-sphere mixtures with q <= 0.1. In all, the new simulation results provide a fully quantitative benchmark for assessing the relative accuracy of theoretical approaches for calculating depletion potentials in highly size-asymmetric mixtures. PMID- 22304070 TI - Power-series expansion of the Boltzmann equation and reciprocal relations for nonlinear irreversible phenomena. AB - The Boltzmann equation subject to a general boundary condition is expanded in a power series with respect to a thermodynamic force disturbing a gaseous system. Recurrence relations between the terms of the expansion are obtained using the main properties of the collision integral and of the gas-surface interaction kernel. The reciprocal relation for nonlinear irreversible phenomena, i.e., a relation between the terms of different orders, is obtained. The relations can be used to estimate the range of applicability of linearized solutions and to predict nonlinear phenomena in gaseous systems. PMID- 22304071 TI - Artificial photosynthetic reaction centers coupled to light-harvesting antennas. AB - We analyze a theoretical model for energy and electron transfer in an artificial photosynthetic system. The photosystem consists of a molecular triad (i.e., with a donor, a photosensitive unit, and an acceptor) coupled to four accessory light harvesting-antenna pigments. The resonant energy transfer from the antennas to the artificial reaction center (the molecular triad) is described here by the Forster mechanism. We consider two different kinds of arrangements of the accessory light-harvesting pigments around the reaction center. The first arrangement allows direct excitation transfer to the reaction center from all the surrounding pigments. The second configuration transmits energy via a cascade mechanism along a chain of light-harvesting chromophores, where only one chromophore is connected to the reaction center. We show that the artificial photosynthetic system using the cascade energy transfer absorbs photons in a broader wavelength range and converts their energy into electricity with a higher efficiency than the system based on direct couplings between all the antenna chromophores and the reaction center. PMID- 22304072 TI - Effectiveness of mixing in violent relaxation. AB - Relaxation processes in collisionless dynamics lead to peculiar behavior in systems with long-range interactions such as self-gravitating systems, non neutral plasmas, and wave-particle systems. These systems, adequately described by the Vlasov equation, present quasistationary states (QSS), i.e., long lasting intermediate stages of the dynamics that occur after a short significant evolution called "violent relaxation." The nature of the relaxation, in the absence of collisions, is not yet fully understood. We demonstrate in this article the occurrence of stretching and folding behavior in numerical simulations of the Vlasov equation, providing a plausible relaxation mechanism that brings the system from its initial condition into the QSS regime. Area preserving discrete-time maps with a mean-field coupling term are found to display a similar behavior in phase space as the Vlasov system. PMID- 22304073 TI - Precise determination of the nonequilibrium tricritical point based on Lynden Bell theory in the Hamiltonian mean-field model. AB - Existence of a nonequilibrium tricritical point has been revealed in the Hamiltonian mean-field model by a nonequilibrium statistical mechanics. This statistical mechanics gives a distribution function containing unknown parameters, and the parameters are determined by solving simultaneous equations depending on a given initial state. Due to difficulty in solving these equations, pointwise numerical detection of the tricritical point has been unavoidable on a plane characterizing a family of initial states. In order to look into the tricritical point, we expand the simultaneous equations with respect to the order parameter and reduce them to one algebraic equation. The tricritical point is precisely identified by analyzing coefficients of the reduced equation. Reentrance to an ordered phase in a high-energy region is revisited around the obtained tricritical point. PMID- 22304074 TI - Exact solution of a heterogeneous multilane asymmetric simple exclusion process. AB - We have proved an exact solution of a multilane totally asymmetric simple exclusion process (TASEP) with heterogeneous lane-changing rates on a torus. In the expression, the TASEP in each lane and lane-changing transition can be separable. Moreover, the lane-changing transitions satisfy the detailed balance condition, and this is the key to constructing the solution. Using the saddle point method, the current of particles has been derived in a simple form in a thermodynamic limit. It is interesting that the dynamics depends only on a set of lane-changing parameters, not on the configuration of lanes. PMID- 22304075 TI - Statistical thermodynamics of straight rigid rods with nonadditive lateral interactions: Theory and Monte Carlo simulations. AB - The statistical thermodynamics of straight rigid rods of length k (k-mers) with nonadditive lateral interactions was developed on a generalization in the spirit of the lattice-gas model and the classical Bragg-Williams approximation (BWA) and the quasichemical approximation (QCA). The new theoretical framework is obtained by combining (i) the exact analytical expression for the partition function of noninteracting linear k-mers adsorbed in one dimension and its extension to higher dimensions, and (ii) a generalization of BWA and QCA in which the adsorbate can occupy more than one adsorption site. The traditional assumption of a strictly pairwise additive nearest-neighbors interaction is replaced by a more general one, namely that the bond linking a certain atom with any of its neighbors depends considerably on how many of them are actually present (or absent) on the sites in the first coordination shell of the atom. The coverage and temperature dependence of the Helmholtz free energy, chemical potential, configurational entropy, and differential heat of adsorption are given. The formalism (i) reproduces the classical results for monomers, (ii) leads to the exact statistical thermodynamics of nonadditive interacting k-mers adsorbed in one dimension, and (iii) provides a close approximation for two-dimensional systems, taking into account multisite occupancy and nonadditive lateral interactions. Comparisons with Monte Carlo simulations are performed in order to test the validity of the theoretical model. Significant quantitative differences are shown and discussed. In all cases, the QCA appears to be the more accurate approach. PMID- 22304076 TI - Asymptotic solutions of decoupled continuous-time random walks with superheavy tailed waiting time and heavy-tailed jump length distributions. AB - We study the long-time behavior of decoupled continuous-time random walks characterized by superheavy-tailed distributions of waiting times and symmetric heavy-tailed distributions of jump lengths. Our main quantity of interest is the limiting probability density of the position of the walker multiplied by a scaling function of time. We show that the probability density of the scaled walker position converges in the long-time limit to a nondegenerate one only if the scaling function behaves in a certain way. This function as well as the limiting probability density are determined in explicit form. Also, we express the limiting probability density which has heavy tails in terms of the Fox H function and find its behavior for small and large distances. PMID- 22304077 TI - O'Connell's process as a vicious Brownian motion. AB - Vicious Brownian motion is a diffusion scaling limit of Fisher's vicious walk model, which is a system of Brownian particles in one dimension such that if two motions meet they kill each other. We consider the vicious Brownian motions conditioned never to collide with each other and call it noncolliding Brownian motion. This conditional diffusion process is equivalent to the eigenvalue process of the Hermitian-matrix-valued Brownian motion studied by Dyson [J. Math. Phys. 3, 1191 (1962)]. Recently, O'Connell [Ann. Probab. (to be published)] introduced a generalization of the noncolliding Brownian motion by using the eigenfunctions (the Whittaker functions) of the quantum Toda lattice in order to analyze a directed polymer model in 1 + 1 dimensions. We consider a system of one dimensional Brownian motions with a long-ranged killing term as a generalization of the vicious Brownian motion and construct the O'Connell process as a conditional process of the killing Brownian motions to survive forever. PMID- 22304078 TI - Simulations of driven and reconstituting lattice gases. AB - We discuss stationary aspects of a set of driven lattice gases in which hard-core particles with spatial extent, covering more than one lattice site, diffuse and reconstruct in one dimension under nearest-neighbor interactions. As in the uncoupled case [M. Barma et al., J. Phys.: Condens. Matter 19, 065112 (2007)], the dynamics of the phase space breaks up into an exponentially large number of mutually disconnected sectors labeled by a nonlocal construct, the irreducible string. Depending on whether the particle couplings are taken attractive or repulsive, simulations in most of the studied sectors show that both steady state currents and pair correlations behave quite differently at low temperature regimes. For repulsive interactions an order-by-disorder transition is suggested. PMID- 22304079 TI - Continuous-time random walks that alter environmental transport properties. AB - We consider continuous-time random walks (CTRWs) in which the walkers have a finite probability to alter the waiting-time and/or step-length transport properties of their environment, resulting in possibly transient anomalous diffusion. We refer to these CTRWs as transmogrifying continuous-time random walks (TCTRWs) to emphasize that they change the form of the transport properties of their environment, and in a possibly strange way. The particular case in which the CTRW waiting-time density has a finite probability to be permanently altered at a given site, following a visitation by a walker, is considered in detail. Master equations for the probability density function of transmogrifying random walkers are derived, and results are compared with Monte Carlo simulations. An interesting finding is that TCTRWs can generate transient subdiffusion or transient superdiffusion without invoking truncated or tempered power law densities for either the waiting times or the step lengths. The transient subdiffusion or transient superdiffusion arises in TCTRWs with Gaussian step length densities and exponential waiting-time densities when the altered average waiting time is greater than or less than, respectively, the original average waiting time. PMID- 22304080 TI - Quantum maximum-entropy principle for closed quantum hydrodynamic transport within a Wigner function formalism. AB - By introducing a quantum entropy functional of the reduced density matrix, the principle of quantum maximum entropy is asserted as fundamental principle of quantum statistical mechanics. Accordingly, we develop a comprehensive theoretical formalism to construct rigorously a closed quantum hydrodynamic transport within a Wigner function approach. The theoretical formalism is formulated in both thermodynamic equilibrium and nonequilibrium conditions, and the quantum contributions are obtained by only assuming that the Lagrange multipliers can be expanded in powers of h(2). In particular, by using an arbitrary number of moments, we prove that (1) on a macroscopic scale all nonlocal effects, compatible with the uncertainty principle, are imputable to high-order spatial derivatives, both of the numerical density n and of the effective temperature T; (2) the results available from the literature in the framework of both a quantum Boltzmann gas and a degenerate quantum Fermi gas are recovered as a particular case; (3) the statistics for the quantum Fermi and Bose gases at different levels of degeneracy are explicitly incorporated; (4) a set of relevant applications admitting exact analytical equations are explicitly given and discussed; (5) the quantum maximum entropy principle keeps full validity in the classical limit, when h -> 0. PMID- 22304081 TI - Cooperation, structure, and hierarchy in multiadaptive games. AB - Game-theoretical models where the rules of the game and the interaction structure both coevolve with the game dynamics--multiadaptive games--capture very flexible situations where cooperation among selfish agents can emerge. In this work, we will discuss a multiadaptive model presented in a recent Letter [Phys. Rev. Lett. 106, 028702 (2011)] as well as generalizations of it. The model captures a nonequilibrium situation where social unrest increases the incentive to cooperate and, simultaneously, agents are partly free to influence with whom they interact. First, we investigate the details of how feedback from the behavior of agents determines the emergence of cooperation and hierarchical contact structures. We also study the stability of the system to different types of noise, and find that different regions of parameter space show very different response. Some types of noise can destroy an all-cooperator (C) state. If, on the other hand, hubs are stable, then so is the all-C state. Finally, we investigate the dependence of the ratio between the time scales of strategy updates and the evolution of the interaction structure. We find that a comparatively fast strategy dynamics is a prerequisite for the emergence of cooperation. PMID- 22304082 TI - Positive congestion effect on a totally asymmetric simple exclusion process with an adsorption lane. AB - We propose a type of asymmetric simple exclusion process by introducing an adsorption lane. In the system, each particle can be adsorbed by the adsorption lane only once per travel. The adsorption and desorption probabilities control the density of adsorption sites and the number of adsorbed particles. The ratio of the adsorbed particles shows reversal dynamics for congestion of the system, which is called the "positive congestion effect." We analyze this phenomenon by simulations and an approximation and successfully derive its critical condition. The spatial distribution of particles controlled by the adsorption and desorption probabilities is also investigated through balance equations of particles. PMID- 22304083 TI - Extremely large-scale simulation of a Kardar-Parisi-Zhang model using graphics cards. AB - The octahedron model introduced recently has been implemented onto graphics cards, which permits extremely large-scale simulations via binary lattice gases and bit-coded algorithms. We confirm scaling behavior belonging to the two dimensional Kardar-Parisi-Zhang universality class and find a surface growth exponent: beta = 0.2415(15) on 2(17) * 2(17) systems, ruling out beta = 1/4 suggested by field theory. The maximum speedup with respect to a single CPU is 240. The steady state has been analyzed by finite-size scaling and a growth exponent alpha = 0.393(4) is found. Correction-to-scaling-exponent are computed and the power-spectrum density of the steady state is determined. We calculate the universal scaling functions and cumulants and show that the limit distribution can be obtained by the sizes considered. We provide numerical fitting for the small and large tail behavior of the steady-state scaling function of the interface width. PMID- 22304084 TI - Self-consistent inhomogeneous steady states in Hamiltonian mean-field dynamics. AB - Long-lived quasistationary states, associated with stationary stable solutions of the Vlasov equation, are found in systems with long-range interactions. Studies of the relaxation time in a model of N globally coupled particles moving on a ring, the Hamiltonian mean-field model (HMF), have shown that it diverges as N(gamma) for large N, with gamma1.7 for some initial conditions with homogeneously distributed particles. We propose a method for identifying exact inhomogeneous steady states in the thermodynamic limit, based on analyzing models of uncoupled particles moving in an external field. For the HMF model, we show numerically that the relaxation time of these states diverges with N with the exponent gamma ~/= 1. The method, applicable to other models with globally coupled particles, also allows an exact evaluation of the stability limit of homogeneous steady states. In some cases, it provides a good approximation for the correspondence between the initial condition and the final steady state. PMID- 22304085 TI - Exponential complexity of the quantum adiabatic algorithm for certain satisfiability problems. AB - We determine the complexity of several constraint satisfaction problems using the quantum adiabatic algorithm in its simplest implementation. We do so by studying the size dependence of the gap to the first excited state of "typical" instances. We find that, at large sizes N, the complexity increases exponentially for all models that we study. We also compare our results against the complexity of the analogous classical algorithm WalkSAT and show that the harder the problem is for the classical algorithm, the harder it is also for the quantum adiabatic algorithm. PMID- 22304086 TI - Bounds and correlation approximation for the effective conductivity of heterogeneous plates. AB - The size effect obtained when studying the effective properties of plates is investigated by producing a third-order correlation approximation and Hashin Shtrikman bounds for the effective in-plane conductivity of heterogeneous plates. The boundary condition of the plates is taken into account by obtaining the exact Green operator for the boundary problem. Results are obtained for a two dimensional (2D) random distribution of disks and a 3D distribution of spheres. All results recover those obtained for an infinite medium when the heterogeneity size becomes small compared to plate thickness. They show that the size effect is more significant in the case of a 2D distribution of heterogeneities than for a 3D distribution. PMID- 22304087 TI - Antiphase synchronization of electrically shaken conducting beads. AB - When a spherical conducting bead is placed in an electrode, it experiences an electric force. In a plane capacitor, it can undergo a periodic bouncing between the electrodes. Using a fast video camera, we measured the acceleration of the bead and the period of its motion as a function of the applied voltage. A mathematical model based on the hypothesis of electrostatic equilibrium is proposed to describe the dynamics of the system. We observe a stabilization of the trajectories: A bead bouncing between two electrodes tends to oscillate on a quasivertical trajectory, whatever its initial horizontal velocity. When two identical beads are placed together in a capacitor, they oscillate at the same frequency and an antiphase synchronization effect occurs. We propose a simple mechanism based on a Kuramoto-like model to explain it. PMID- 22304088 TI - Lift force on an asymmetrical obstacle immersed in a dilute granular flow. AB - This paper investigates the lift force exerted on an elliptical obstacle immersed in a granular flow through analytical calculations and computer simulations. The results are shown as a function of the obstacle size, orientation with respect to the flow direction (tilt angle), the restitution coefficient and ellipse eccentricity. The theoretical argument, based on the force exerted on the obstacle due to inelastic, frictionless collisions of a very dilute flow, captures the qualitative features of the lift, but fails to reproduce the data quantitatively. The reason behind this disagreement is that the dilute flow assumption on which this argument is built breaks down as a granular shock wave forms in front of the obstacle. More specifically, the shock wave changes the grains impact velocity at the obstacle, decreasing the overall net lift obtained from a very dilute flow. PMID- 22304089 TI - Creep motion of a model frictional system. AB - We report on the dynamics of a model frictional system submitted to minute external perturbations. The system consists of a chain of sliders connected through elastic springs that rest on an incline. By introducing cyclic expansions and contractions of the springs we observe a reptation of the chain. We account for the average reptation velocity theoretically. The velocity of small systems exhibits a series of plateaus as a function of the incline angle. Due to elastic effects, there exists a critical amplitude below which the reptation is expected to cease. However, rather than a full stop of the creep, we observe in numerical simulations a transition between a continuous-creep and an irregular-creep regime when the critical amplitude is approached. The latter transition is reminiscent of the transition between the continuous and the irregular compaction of granular matter submitted to periodic temperature changes. PMID- 22304090 TI - Simulations of thermophoretic nanoswimmers. AB - We consider a nanodimer in solution with asymmetric thermal properties that shows self-propelled motion. One monomer of the nanodimer can be heated to a fixed temperature producing a radially symmetric temperature gradient. The thermophoretic properties of the second monomer produce then a propulsion against or toward the heated particle, such that the nanodimer becomes a puller or pusher nanoswimmer. We combine our simulation measurements with a theoretical analysis that satisfactorily characterizes the self-propelled velocity with the temperature gradient, and the thermophoretic properties of the bead. PMID- 22304091 TI - Mode-coupling glass transition in a fluid confined by a periodic potential. AB - We show that a fluid under strong spatially periodic confinement displays a glass transition within mode-coupling theory at a much lower density than the corresponding bulk system. We use fluctuating hydrodynamics, with confinement imposed through a periodic potential whose wavelength plays an important role in our treatment. To make the calculation tractable we implement a detailed calculation in one dimension. Although we do not expect simple 1d fluids to show a glass transition, our results are indicative of the behavior expected in higher dimensions. In a certain region of parameter space we observe a three-step relaxation reported recently in computer simulations [S. H. Krishnan, Ph.D. thesis, Indian Institute of Science (2005); Kim et al., Eur. Phys. J. Special Topics 189, 135 (2010)] and a glass-glass transition. We compare our results to those of Krakoviack [Phys. Rev. E 75, 031503 (2007)] and Lang et al. [Phys. Rev. Lett. 105, 125701 (2010)]. PMID- 22304092 TI - Mode-coupling theory for the glass transition: test of the convolution approximation for short-range interactions. AB - We reexamine the convolution approximation commonly used in the mode-coupling theory (MCT) of nonergodic states of classical fluids. This approximation concerns the static correlation functions used as input in the MCT treatment of the dynamics. Besides the hard-sphere model, we consider interaction potentials that present a short-range tail, either attractive or repulsive, beyond the hard core. By using accurate static correlation functions obtained from the fundamental measures functional for hard spheres, we show that the role of three body direct correlations can be more significant than what is inferred from previous simple ansatzs for pure hard spheres. This may in particular impact the location of the glass transition line and the nonergodicity parameter. PMID- 22304093 TI - Direct evidence of heterogeneous mechanical relaxation in supercooled liquids. AB - Dynamic heterogeneity is now considered to be an intrinsic kinetic feature of a supercooled liquid. Here, we access the nonlocal complex modulus of a glass forming liquid using molecular dynamics simulations. We find that the shear stress relaxation exhibits a marked wave number dependence in a supercooled state. This dependence provides direct evidence that slow mechanical relaxation takes place heterogeneously in space. Its characteristic length xi increases with decreasing temperature and becomes mesoscopic. The response involves particle rearrangements over xi and takes a time comparable to the structural relaxation time tau(alpha). Our finding suggests that the heterogeneous structural relaxation is of fundamental importance in anomalous viscous transport and viscoelasticity in supercooled liquids. PMID- 22304094 TI - Deionization shocks in microstructures. AB - Salt transport in bulk electrolytes is limited by diffusion and advection, but in microstructures with charged surfaces (e.g., microfluidic devices, porous media, soils, or biological tissues) surface conduction and electro-osmotic flow also contribute to ionic fluxes. For small applied voltages, these effects lead to well known linear electrokinetic phenomena. In this paper, we predict some surprising nonlinear dynamics that can result from the competition between bulk and interfacial transport at higher voltages. When counterions are selectively removed by a membrane or electrode, a "deionization shock" can propagate through the microstructure, leaving in its wake an ultrapure solution, nearly devoid of coions and colloidal impurities. We elucidate the basic physics of deionization shocks and develop a mathematical theory of their existence, structure, and stability, allowing for slow variations in surface charge or channel geometry. Via asymptotic approximations and similarity solutions, we show that deionization shocks accelerate and sharpen in narrowing channels, while they decelerate and weaken, and sometimes disappear, in widening channels. These phenomena may find applications in separations (deionization, decontamination, biological assays) and energy storage (batteries, supercapacitors) involving electrolytes in microstructures. PMID- 22304095 TI - Boundary effect in electrorheological fluids. AB - The effect of the boundary friction coefficient on the rheological properties of the electrorheological (ER) fluids in quasistatic and dynamic states is investigated by computer simulation. The relation between the shear stress and the boundary friction coefficient in quasistatic and dynamic states is discussed qualitatively and quantitatively, and the trend matches the previously reported experimental results well. The flow curves of ER fluids, under different friction coefficients, are calculated, and it is found that the friction coefficient affects the flow curves. In two dimensions, the transitions in structure corresponding to the shear stress variations are presented to understand the mechanism of ER fluids. PMID- 22304096 TI - Elastocapillary instability under partial wetting conditions: bending versus buckling. AB - The elastocapillary instability of a flexible plate plunged in a liquid bath is analyzed theoretically. We show that the plate can bend due to two separate destabilizing mechanisms, when the liquid is partially wetting the solid. For contact angles theta(e) > pi/2, the capillary forces acting tangential to the surface are compressing the plate and can induce a classical buckling instability. However, a second mechanism appears due to capillary forces normal to surface. These induce a destabilizing torque that tends to bend the plate for any value of the contact angle theta(e) > 0. We denote these mechanisms as "buckling" and "bending," respectively and identify the two corresponding dimensionless parameters that govern the elastocapillary stability. The onset of instability is determined analytically and the different bifurcation scenarios are worked out for experimentally relevant conditions. PMID- 22304097 TI - Wetting and contact-line effects for spherical and cylindrical droplets on graphene layers: a comparative molecular-dynamics investigation. AB - In molecular dynamics (MD) simulations, interactions between water molecules and graphitic surfaces are often modeled as a simple Lennard-Jones potential between oxygen and carbon atoms. A possible method for tuning this parameter consists of simulating a water nanodroplet on a flat graphitic surface, measuring the equilibrium contact angle, extrapolating it to the limit of a macroscopic droplet, and finally matching this quantity to experimental results. Considering recent evidence demonstrating that the contact angle of water on a graphitic plane is much higher than what was previously reported, we estimate the oxygen carbon interaction for the recent SPC/Fw water model. Results indicate a value of about 0.2 kJ/mol, much lower than previous estimations. We then perform simulations of cylindrical water filaments on graphitic surfaces, in order to compare and correlate contact angles resulting from these two different systems. Results suggest that a modified Young's equation does not describe the relation between contact angle and drop size in the case of extremely small systems and that contributions different from the one deriving from contact line tension should be taken into account. PMID- 22304098 TI - Random sequential adsorption of partially oriented linear k-mers on a square lattice. AB - Jamming phenomena on a square lattice are investigated for two different models of anisotropic random sequential adsorption (RSA) of linear k-mers (particles occupying k adjacent adsorption sites along a line). The length of a k-mer varies from 2 to 256. The effect of k-mer alignment on the jamming threshold is examined. For completely ordered systems where all the k-mers are aligned along one direction (e.g., vertical), the obtained simulation data are very close to the known analytical results for one-dimensional systems. In particular, the jamming threshold tends to the Renyi's parking constant for large k. In the other extreme case, when k-mers are fully disordered, our results correspond to the published results for short k-mers. It was observed that for partially oriented systems the jamming configurations consist of the blocks of vertically and horizontally oriented k-mers (v and h blocks, respectively) and large voids between them. The relative areas of different blocks and voids depend on the order parameter s, k-mer length, and type of the model. For small k-mers (k?4), denser configurations are observed in disordered systems as compared to those of completely ordered systems. However, longer k-mers exhibit the opposite behavior. PMID- 22304099 TI - Effect of immobile impurities on motion of steps on a vicinal face. AB - We carry out Monte Carlo simulations and study the dependence of the behaviors of steps on impurities on a vicinal face. We assume that the impurities are immobile and the lifetime of them is much longer than that of adatoms. During growth, the impurities in front of a step prevent the step from advancing. If a wide terrace appears due to the fluctuations of step positions, the number of impurities on the terrace is more than other terraces. The step at the upper side of the wide terrace is slower than other steps, so that an equidistant train of steps becomes unstable. In our Monte Carlo simulations, with steps gathering and separating repeatedly, the bunches of steps are formed on the unstable surface. PMID- 22304100 TI - Nonlinear dynamics of a thin nonisothermal liquid film on an axially oscillating cylindrical surface. AB - The nonlinear dynamics of a nonisothermal thin liquid film on a horizontal cylindrical surface subjected to axial harmonic vibration is investigated in this paper. It is found that the capillary instability of an axisymmetric film on a still cylinder can be saturated via the Marangoni effect by heating the film at the gas side, similar to the saturation of the Rayleigh-Taylor instability in the planar case. If the capillary instability is not saturated by the Marangoni effect, the combined capillary-Marangoni instability can be saturated by the harmonic axial forcing provided that the forcing amplitude exceeds a certain critical value depending on the rest of parameters. The critical amplitude is demonstrated to increase with the Marangoni number when other parameters are fixed. The critical forcing amplitude at a given forcing frequency is shown to be well approximated by a piecewise linear function of the Marangoni number. PMID- 22304101 TI - Geometric evolution law for modeling strongly anisotropic thin-film morphology. AB - The morphology of the solid-vapor interface of a nanoscale thin crystalline film is influenced by many factors including surface diffusion, attachment-detachment, deposition, and interface kinetics. Using a high-order accurate and efficient numerical method, we investigate the dynamics of two dimensional thin films when all of these effects are considered. The observed morphologies consist of facets of constant slope separated by narrow transition intervals: kinks (valleys) and antikinks (hills). The number of kinks and antikinks decreases as the system coarsens in time. Our numerical results confirm that when deposition is present, the only possible coarsening event is the kink-ternary where two kinks meet and annihilate an antikink. We characterize the total amount of coarsening, the time over which the coarsening occurs and the associated coarsening scaling laws when all effects are considered. As found in previous work that considered only attachment-detachment, or surface diffusion, there are three distinct coarsening regimes associated with increasing magnitudes of the deposition flux-fast coarsening, a regime in which periodic structures form with little or no subsequent coarsening, and a regime in which the film surface evolves chaotically. We find that the inclusion of attachment-detachment leads to additional coarsening compared to the dynamics that result from driven surface diffusion alone. When deposition and interface kinetics are both considered, the slowdown of evolution caused by the kinetic effects necessitates a decrease in the deposition flux in order to produce a nonchaotic coarsening regime. Together, these provide testable predictions for experiments of thin-film dynamics. PMID- 22304102 TI - Thermodynamic properties of a symmetrical binary mixture in the coexistence region. AB - A three-dimensional symmetric binary fluid is studied, as a function of temperature, in the two-phase (liquid-liquid) coexistence region via Monte Carlo simulations. Particular focus has been in the understanding of curvature dependent interfacial tension, which is observed to vary as sigma(R) = sigma(infinity)/[1+2(l/R)(2)], implying that a Tolman length is zero in the limit R -> infinity. The length l is found to have a critical divergence the same as the correlation length, but its amplitude is significantly larger (l ~/= 4xi). Our findings hence imply that the barrier against homogeneous nucleation is significantly reduced (in comparison with the classical nucleation theory) in the critical region. We also report results for the critical behavior of the flat interfacial tension sigma(infinity) and the concentration susceptibility, as well as the amplitude ratios involving these thermodynamic quantities. Noting that the interatomic potential in our model is described by the Lennard-Jones form that decays faster that 1/r(3), all of our results for critical phenomena are expectedly consistent with the Ising universality class of three spatial dimensions. PMID- 22304103 TI - Stripe and line textures in the B2 phase of bent-shape molecules in samples with polar surface anchoring. AB - In the B2 phase formed by bent-shaped molecules a dense line texture is frequently observed. For the texture description a model is proposed consisting of a periodic system of anticlinic antiferroelectric bulk domains with opposite chiralities separated by pi walls in which polarization rotates. The bulk domains are situated between layers of synclinic ferroelectric phase near the upper and lower surfaces. In the surface layers induced by polar anchoring domains of opposite chirality are separated by defect lines. Under the electric field the ferroelectric layer near one sample surface is growing against the antiferroelectric structure in the sample bulk and the stripe texture is fading out, but still in the saturated field surface lines or walls persist separating ferroelectric domains of opposite chirality. The proposed model is adapted also for a case when the anticlinic antiferroelectric structure in the sample bulk is sandwiched between anticlinic ferroelectric layers near the surfaces. In that case the applied electric field eliminates all the lines because the resulting anticlinic ferroelectric structure is racemic, with no chiral domains. PMID- 22304104 TI - Computing with liquid crystal fingers: models of geometric and logical computation. AB - When a voltage is applied across a thin layer of cholesteric liquid crystal, fingers of cholesteric alignment can form and propagate in the layer. In computer simulation, based on experimental laboratory results, we demonstrate that these cholesteric fingers can solve selected problems of computational geometry, logic, and arithmetics. We show that branching fingers approximate a planar Voronoi diagram, and nonbranching fingers produce a convex subdivision of concave polygons. We also provide a detailed blueprint and simulation of a one-bit half adder functioning on the principles of collision-based computing, where the implementation is via collision of liquid crystal fingers with obstacles and other fingers. PMID- 22304105 TI - Rigid probe solutes in a smectic-A liquid crystal: an unconventional route to the latter's positional order parameters. AB - Biphenylene and pyrene were dissolved in the nematic and smectic-A phases of the liquid crystal 4,4'-di-n-heptyl-azoxybenzene and the orientational order parameters of both solutes and solvent measured via proton and deuteron nuclear magnetic-resonance spectroscopy. This new data set was then merged with the one previously obtained, formed by 4,4'-di-chloro-benzene and naphthalene as solutes in the same solvent, and the resulting overall data set analyzed with a statistical thermodynamic density-functional theory to provide positional orientational distribution functions of the various solutes along with the smectic solvent's positional order parameters. PMID- 22304106 TI - Binary mixtures of liquid crystalline compounds with a reentrant smectic-A* phase. AB - Binary mixtures of chiral liquid crystalline homologs have been studied. One compound designated 9ZBL exhibited reentrancy of a paraelectric smectic-A* phase, SmA*(RE), below the ferroelectric SmC* phase in the SmA*-SmC*-SmA*RE phase sequence. Stabilization of the SmA(RE) phase is established from studying binary mixtures of 9ZBL with its neighboring homologs 8ZBL and 10ZBL. Compound 8ZBL exhibits only SmA* phase in a wide temperature range and for 10ZBL the SmA*-SmC* phase sequence is observed on cooling. X-ray studies, dielectric spectroscopy, polarization, and tilt angle measurements have been carried out to characterize studied materials. For binary mixtures 9ZBL-10ZBL the reentrant SmA_(RE*) phase is observed for all studied concentrations. For binary mixtures 9ZBL-8ZBL a very small amount of 8ZBL (up to 0.5 mole %) causes disappearance of the SmC* phase. Nevertheless, a small anomaly in the temperature dependencies of the layer spacing, d(T), accompanied by a significant decrease in diffracted x-ray intensity occurs within the SmA* phase for mixtures containing up to 20 mole % of 8ZBL. This anomaly is evidence of the existence of a boundary between the SmA* and SmA(RE*) phases, thus proving their different nature. PMID- 22304107 TI - Memory effect in composites of liquid crystal and silica aerosil. AB - Aerosil silica nanoparticles dispersed in a liquid crystal (LC) possess the interesting property of keeping memory of an electric- or magnetic-field-induced orientation. Two types of memory have been identified: thermally erasable memory arising from the pinning of defect lines versus a "permanent" memory where the orientation persists even after thermal cycling the samples up to the isotropic phase. To address the source of the latter type of memory, solid-state nuclear magnetic resonance spectroscopy and conventional x-ray diffraction (XRD) were first combined to characterize the LC orientational order as a function of multiple in-field temperature cycles. Microbeam XRD was then performed on aligned gels of different concentrations to gain knowledge of the structural properties at the origin of the memory effect. No detectable anisotropy of the gel or significant breaking of silica strands with heating ruled out the formation of an anisotropic silica network as the source of the permanent memory as previously proposed. Instead, support for a role of the surface memory effect, well known for planar substrates, in stabilizing the permanent memory was deduced from "training" of the composites, that is, optimizing the orientational order through the thermal in-field cycling. The ability to train the composites is inversely proportional to the strength of the random-field disorder. The portion of thermally erasable memory also decreases as the silica density increases. We propose that the permanent memory originates from the surface memory effect operating at points of intersection in the silica network. These areas, where the LC is strongly confined with conflicted surface interactions, are trained to achieve an optimized orientation and subsequently act as sites from which the LC orientational order regrows after zero-field thermal cycling up to the isotropic phase. PMID- 22304108 TI - Crossover from tricritical to critical end point behavior in free-standing smectic films. AB - We study the smectic to nematic (SmA-N) phase transition taking place at the center of a free-standing film that exhibits enhanced surface order due to the anchoring promoted by a surrounding gas. The usual McMillan mean-field approach predicts that the SmA-N transition in bulk samples can be continuous or discontinuous (first or second order) depending on the molecular geometry, with a tricritical point separating these two regimes. Here we show that the additional orientational order imposed by the surface anchoring stabilizes the surface induced smectic and nematic phases, leading to the breakdown of the tricritical point and to the emergence of a critical end point. We report the full phase diagram, which depicts four distinct structures as the film thickness is reduced. PMID- 22304109 TI - Aggregation kinetics of a simulated telechelic polymer. AB - We investigate the aggregation kinetics of a simulated telechelic polymer gel. In the hybrid molecular dynamics (MD)/Monte Carlo (MC) algorithm, aggregates of associating end groups form and break according to MC rules, while the position of the polymers in space is dictated by MD. As a result, the aggregate sizes change over time. In order to describe this aggregation process, we employ master equations. They define changes in the number of aggregates of a certain size in terms of reaction rates. These reaction rates indicate the likelihood that two aggregates combine to form a large one, or that a large aggregate splits into two smaller parts. The reaction rates are obtained from the simulations for a range of temperatures. Our results indicate that the rates are not only temperature dependent, but also a function of the sizes of the aggregates involved in the reaction. Using the measured rates, solutions to the master equations are shown to be stable and in agreement with the aggregate size distribution, as obtained directly from simulation data. Furthermore, we show how temperature-induced variations in these rates give rise to the observed changes in the aggregate distribution that characterizes the sol-gel transition. PMID- 22304110 TI - Effect of viscoelasticity on the collective behavior of swimming microorganisms. AB - Hydrodynamic interactions of swimming microorganisms can lead to coordinated behaviors of large groups. Using a mean-field theory and the Oldroyd-B constitutive equation, we show how linear viscoelasticity of the suspending fluid alters the hydrodynamic interactions and therefore the ability of the group to coordinate. We quantify the ability to coordinate by the initial growth rate of a small disturbance from the uniform isotropic state. For small wave numbers the response is qualitatively similar to a Newtonian fluid but the Deborah number affects an effective viscosity of the suspension. At higher wave number, the response of the fluid to small amplitude oscillatory shear flow, leads to a maximal growth rate at a particular wavelength unlike the Newtonian result. PMID- 22304111 TI - Fiber-probe detection for positron-emission-assisted Cherenkov-radiation brain mapping. AB - Suitably designed optical fibers are shown to offer a powerful tool for functional brain mapping, facilitating the detection of Cherenkov radiation generated by relativistic positrons from positron-emitting radionuclides. Fiber probes support a low-loss delivery of the high-intensity short-wavelength part of the Cherenkov spectrum, which is strongly absorbed by biotissues, and lower the threshold positron energy epsilon required for Cherenkov radiation relative to epsilon values typical of biotissues, thus enhancing the conversion of positron energy into Cherenkov radiation. PMID- 22304112 TI - Attractive double-layer forces between neutral hydrophobic and neutral hydrophilic surfaces. AB - The interaction between surface patches of proteins with different surface properties has a vital role to play driving conformational changes in proteins in different salt solutions. We demonstrate the existence of ion-specific attractive double-layer forces between neutral hydrophobic and hydrophilic surfaces in the presence of certain salt solutions. This is performed by solving a generalized Poisson-Boltzmann equation for two unequal surfaces. In the calculations, we utilize parametrized ion-surface potentials and dielectric-constant profiles deduced from recent non-primitive-model molecular dynamics simulations that partially account for molecular structure and hydration effects. PMID- 22304113 TI - Time-resolved small-angle x-ray scattering study of the early stage of amyloid formation of an apomyoglobin mutant. AB - The description of the fibrillogenesis pathway and the identification of "on pathway" or "off-pathway" intermediates are key issues in amyloid research as they are concerned with the mechanism for onset of certain diseases and with therapeutic treatments. Recent results on the fibril formation process revealed an unexpected complexity both in the number and in the types of species involved, but the early aggregation events are still largely unknown, mainly because of their experimental inaccessibility. To provide information on the early stage events of self-assembly of an amyloidogenic protein, during the so-called lag phase, stopped-flow time-resolved small angle x-ray scattering (SAXS) experiments were performed. Using a global fitting analysis, the structural and aggregation properties of the apomyoglobin W7FW14F mutant, which is monomeric and partly folded at acidic pH but forms amyloid fibrils after neutralization, were derived from the first few milliseconds onward. SAXS data indicated that the first aggregates appear in less than 20 ms after the pH jump to neutrality and further revealed the simultaneous presence of diverse species. In particular, worm-like unstructured monomers, very large assemblies, and elongated particles were detected, and their structural features and relative concentrations were derived as a function of time on the basis of our model. The final results show that, during the lag phase, early assembling occurs due to the presence of transient monomeric species very prone to association and through successive competing aggregation and rearrangement processes leading to coexisting on-pathway and off pathway transient species. PMID- 22304114 TI - Energetics of synchronized states in three-dimensional beating flagella. AB - During collective locomotion, beating flagella of spermatozoa interact hydrodynamically and are observed experimentally to synchronize. G. I. Taylor used a small-amplitude two-dimensional sheet model to show that the rate at which swimmers do work against the fluid is minimal for in-phase beating. We use a semianalytical approach based on hydrodynamic reflections to extend these results to the small-amplitude three-dimensional beating of infinite flagellar filaments. We first consider a configuration of two parallel filaments. In the case where the beating of both flagella occurs in the same plane as that defined by their axis, in-phase beating is found to lead to an overall minimum of energy dissipation, while opposite-phase leads to a maximum. If we allow the orientation of the beating planes to vary, we find that the minimum of energy dissipation is obtained for either the in-phase or opposite-phase conformation, in a manner that depends on the flagella orientation and their relative distance. We further characterize numerically the set of optimal relative orientations. Quantitatively analogous results are obtained using a simple model based on the beating of two spheres interacting hydrodynamically in the far field. Exploiting the linearity of Stokes equation, we then extend our results to the case of three beating flagella in an aligned and triangular conformation. Consistent with Taylor's two dimensional work, our results suggest that, from a hydrodynamic standpoint, it is more energetically favorable for spermatozoa with three-dimensional flagella to swim close to each other and with synchronized, parallel, in-phase beating. PMID- 22304115 TI - Mechanics of soft composites of rods in elastic gels. AB - We report detailed theoretical investigations of the micromechanics and bulk elastic properties of composites consisting of randomly distributed stiff fibers embedded in an elastic matrix in two and three dimensions. Recent experiments [V. Pelletier, N. Gal, P. Fournier, and M. L. Kilfoil, Phys. Rev. Lett. 102, 188303 (2009)] have suggested that the inclusion of stiff microtubules in a softer, nearly incompressible biopolymer matrix can lead to emergent compressibility. This can be understood in terms of the enhancement of the compressibility of the composite relative to its shear compliance as a result of the addition of stiff rodlike inclusions. We show that the Poisson's ratio nu of such a composite evolves with increasing rod density toward a particular value, or fixed point, independent of the material properties of the matrix, as long as it has a finite initial compressibility. This fixed point is nu = 1/4 in three dimensions and nu = 1/3 in two dimensions. Our results suggest an important role for stiff filaments such as microtubules and stress fibers in cell mechanics. At the same time, our work has a wider elasticity context, with potential applications to composite elastic media with a wide separation of scales in stiffness of its constituents such as carbon nanotube-polymer composites, which have been shown to have highly tunable mechanics. PMID- 22304116 TI - Mechanochemical model of cell migration on substrates of varying stiffness. AB - Cells propel themselves along a substrate by organizing structures at the leading edge called lamellipodia that contain the actin network, myosin, integrin, and other proteins. In this article, we describe a quantitative model that couples the response of stretch-sensitive proteins in the lamellipodia to the dynamics of the actin cytoskeleton, therefore allowing the cell to respond to different substrate stiffnesses. Using this model, we predict the various phases of dynamics possible, including continuous protrusion, unstable retractions leading to ruffling, and periodic protrusion-retraction cycles. We explain the necessary conditions for each type of migratory behavior to occur. In particular, we show that, for periodic protrusion-retraction cycles to occur, the stiffness of the substrate must be high, the myosin-dependent maturation rate of nascent to focal adhesions must be high, and the myosin-independent integrin activation rate must be low. In addition, we also predict the dynamics expected at a given substrate stiffness, leading to a quantitative explanation of experimental data that showed that periodic protrusion-retraction cycles disappear when cells are placed on soft substrates. We also suggest experiments with downregulating alpha actinin and/or talin and upregulating p130Cas and make predictions on what types of migratory dynamics will be observed. PMID- 22304117 TI - Computational and experimental study of chemotaxis of an ensemble of bacteria attached to a microbead. AB - Micro-objects propelled by whole cell actuators, such as flagellated bacteria, are being increasingly studied and considered for a wide variety of applications. In this work we present theoretical and experimental investigations of chemotactic motility of a 10 MUm diameter microbead propelled by an ensemble of attached flagellated bacteria. The stochastic model presented here encompasses the behavior of each individual bacterium attached to the microbead in a spatiotemporally varying chemoattractant field. The computational model shows that in a chemotactic environment, the ensemble of bacteria, although constrained, propel the bead in a chemotactic manner with a 67% enhancement in displacement to distance ratio (defined as directionality) compared to nonchemotactic propulsion. The simulation results are validated experimentally. Close agreement between theory and experiments demonstrates the possibility of using the presented model as a predictive tool for other similar biohybrid systems. PMID- 22304118 TI - Membrane morphology induced by anisotropic proteins. AB - There are a great many proteins that localize to and collectively generate curvature in biological fluid membranes. We study changes in the topology of fluid membranes due to the presence of highly anisotropic, curvature-inducing proteins. Generically, we find a surprisingly rich phase diagram with phases of both positive and negative Gaussian curvature. As a concrete example modeled on experiments, we find that a lamellar phase in a negative Gaussian curvature regime exhibits a propensity to form screw dislocations of definite Burgers scalar but of both chiralities. PMID- 22304119 TI - Equilibrium properties of realistic random heteropolymers and their relevance for globular and naturally unfolded proteins. AB - Random heteropolymers do not display the typical equilibrium properties of globular proteins, but are the starting point to understand the physics of proteins and, in particular, to describe their non-native states. So far, they have been studied with mean-field models in the thermodynamic limit, or with computer simulations of very small chains on lattice. After describing a self adjusting parallel-tempering technique to sample efficiently the low-energy states of frustrated systems without the need of tuning the system-dependent parameters of the algorithm, we apply it to random heteropolymers moving in continuous space. We show that if the mean interaction between monomers is negative, the usual description through the random-energy model is nearly correct, provided that it is extended to account for noncompact conformations. If the mean interaction is positive, such a simple description breaks out and the system behaves in a way more similar to Ising spin glasses. The former case is a model for the denatured state of globular proteins, the latter of naturally unfolded proteins, whose equilibrium properties thus result as qualitatively different. PMID- 22304120 TI - Suppressing epidemics with a limited amount of immunization units. AB - The way diseases spread through schools, epidemics through countries, and viruses through the internet is crucial in determining their risk. Although each of these threats has its own characteristics, its underlying network determines the spreading. To restrain the spreading, a widely used approach is the fragmentation of these networks through immunization, so that epidemics cannot spread. Here we develop an immunization approach based on optimizing the susceptible size, which outperforms the best known strategy based on immunizing the highest-betweenness links or nodes. We find that the network's vulnerability can be significantly reduced, demonstrating this on three different real networks: the global flight network, a school friendship network, and the internet. In all cases, we find that not only is the average infection probability significantly suppressed, but also for the most relevant case of a small and limited number of immunization units the infection probability can be reduced by up to 55%. PMID- 22304121 TI - Kinetic Monte Carlo method applied to nucleic acid hairpin folding. AB - Kinetic Monte Carlo on coarse-grained systems, such as nucleic acid secondary structure, is advantageous for being able to access behavior at long time scales, even minutes or hours. Transition rates between coarse-grained states depend upon intermediate barriers, which are not directly simulated. We propose an Arrhenius rate model and an intermediate energy model that incorporates the effects of the barrier between simulated states without enlarging the state space itself. Applying our Arrhenius rate model to DNA hairpin folding, we demonstrate improved agreement with experiment compared to the usual kinetic Monte Carlo model. Further improvement results from including rigidity of single-stranded stacking. PMID- 22304122 TI - Fast wandering of slow birds. AB - I study a single slow bird moving with a flock of birds of a different and faster (or slower) species. I find that every species of flocker has a characteristic speed gamma ? v(0), where v(0) is the mean speed of the flock such that if the speed v(s) of the slow bird equals gamma, it will randomly wander transverse to the mean direction of flock motion far faster than the other birds will: Its mean squared transverse displacement will grow in d = 2 with time t like t(5/3), in contrast to t(4/3) for the other birds. In d = 3, the slow bird's mean-squared transverse displacement grows like t(5/4), in contrast to t for the other birds. If v(s) ? gamma, the mean-squared displacement of the slow bird crosses over from t(5/3) to t(4/3) scaling in d = 2 and from t(5/4) to t scaling in d = 3 at a time t(c) that scales according to t(c) proportionally |v(s) - gamma|(-2). PMID- 22304123 TI - Correlation transfer in stochastically driven neural oscillators over long and short time scales. AB - In the absence of synaptic coupling, two or more neural oscillators may become synchronized by virtue of the statistical correlations in their noisy input streams. Recent work has shown that the degree of correlation transfer from input currents to output spikes depends not only on intrinsic oscillator dynamics, but also on the length of the observation window over which the correlation is calculated. In this paper we use stochastic phase reduction and regular perturbations to derive the correlation of the total phase elapsed over long time scales, a quantity that provides a convenient proxy for the spike count correlation. Over short time scales, we derive the spike count correlation directly using straightforward probabilistic reasoning applied to the density of the phase difference. Our approximations show that output correlation scales with the autocorrelation of the phase resetting curve over long time scales. We also find a concise expression for the influence of the shape of the phase resetting curve on the initial slope of the output correlation over short time scales. These analytic results together with numerical simulations provide new intuitions for the recent counterintuitive finding that type I oscillators transfer correlations more faithfully than do type II over long time scales, while the reverse holds true for the better understood case of short time scales. PMID- 22304124 TI - Pulmonary diffusional screening and the scaling laws of mammalian metabolic rates. AB - Theoretical considerations suggest that the mammalian metabolic rate is linearly proportional to the surface areas of mitochondria, capillary, and alveolar membranes. However, the scaling exponents of these surface areas to the mammals' body mass (approximately 0.9-1) are higher than exponents of the resting metabolic rate (RMR) to body mass (approximately 0.75), although similar to the one of exercise metabolic rate (EMR); the underlying physiological cause of this mismatch remains unclear. The analysis presented here shows that discrepancies between the scaling exponents of RMR and the relevant surface areas may originate from, at least for the system of alveolar membranes in mammalian lungs, the facts that (i) not all of the surface area is involved in the gas exchange and (ii) that larger mammals host a smaller effective surface area that participates in the material exchange rate. A result of these facts is that lung surface areas unused at rest are activated under heavy breathing conditions (e.g., exercise), wherein larger mammals support larger activated surface areas that provide a higher capability to increase the gas-exchange rate, allowing for mammals to meet, for example, the high energetic demands of foraging and predation. PMID- 22304125 TI - Gel electrophoresis of linear and star-branched DNA. AB - The electrophoretic mobility of double-stranded DNA in polyacrylamide gel is investigated using an activated hopping model for the transport of a charged object within a heterogeneous medium. The model is premised upon a representation of the DNA path through the gel matrix as a series of traps with alternating large and small cross sections. Calculations of the trap dimensions from gel data show that the path imposes varying degrees of confinement upon migrating analytes, which retard their forward motion in a size-dependent manner. An expression derived for DNA mobility is shown to provide accurate predictions for the dynamics of linear DNA (67-622 bp) in gels of multiple concentrations. For star-branched DNA, the incorporation within the model of a length scale previously proposed to account for analyte architecture [Yuan et al., Anal. Chem. 78, 6179 (2006)] leads to mobility predictions that compare well with experimental results for a wide range of DNA shapes and molecular weights. PMID- 22304126 TI - Genesis of two-dimensional patterns in cross-gradient fields. AB - Tissue morphogenesis is controlled by the two-dimensional patterning of gene expression in epithelial layers, that determines cell fates. The mechanisms of pattern formation involve intracellular regulatory networks controlled by paracrine and autocrine signaling. We develop a general logical scheme to deduce the morphology of two-dimensional patterns in the field of two crossed morphogen gradients enriched by the action of autocrine signaling that may subdivide expression domains in nontrivial ways. A variety of persistent patterns, either stationary or oscillatory, are generated using the various interaction schemes, some of which have been generated by a special algorithm including random inputs and selected according to suitable criteria. We give the full classification of a variety of stationary and oscillatory expression patterns in the presence of a single autocrine signal based on logical arguments. These results are further confirmed by numerical computations based on reaction-diffusion equations for morphogens and ligands and the discrete (cell-level) description of intracellular dynamics. Model simulations also elucidate transient processes, in particular interaction schemes. Different internal schemes may lead to identical persistent patterns, although relaxation may proceed in distinct ways. As an illustration of the general method, we test a particular scheme suggested by genetic studies of dynamic gene expression patterns in the follicular epithelium of the Drosophila eggshell. PMID- 22304127 TI - Multivariate multiscale entropy: a tool for complexity analysis of multichannel data. AB - This work generalizes the recently introduced univariate multiscale entropy (MSE) analysis to the multivariate case. This is achieved by introducing multivariate sample entropy (MSampEn) in a rigorous way, in order to account for both within- and cross-channel dependencies in multiple data channels, and by evaluating it over multiple temporal scales. The multivariate MSE (MMSE) method is shown to provide an assessment of the underlying dynamical richness of multichannel observations, and more degrees of freedom in the analysis than standard MSE. The benefits of the proposed approach are illustrated by simulations on complexity analysis of multivariate stochastic processes and on real-world multichannel physiological and environmental data. PMID- 22304128 TI - Scale-free duplication dynamics: a model for ultraduplication. AB - Empirical studies of the genome-wide length distribution of duplicated sequences have revealed an algebraic tail common to nearly all clades. The decay of the tail is often well approximated by a single exponent that takes values within a limited range. We propose and study here scale-free duplication dynamics, a class of model for genome sequence evolution that generates the observed shapes of this distribution. A transition between self-similar and non-self-similar regimes is exhibited. Our model accounts plausibly for the observed form of the algebraic tail, which is not produced by standard models for generating long-range sequence correlations. PMID- 22304129 TI - Velocity-jump models with crowding effects. AB - Velocity-jump processes are discrete random-walk models that have many applications including the study of biological and ecological collective motion. In particular, velocity-jump models are often used to represent a type of persistent motion, known as a run and tumble, that is exhibited by some isolated bacteria cells. All previous velocity-jump processes are noninteracting, which means that crowding effects and agent-to-agent interactions are neglected. By neglecting these agent-to-agent interactions, traditional velocity-jump models are only applicable to very dilute systems. Our work is motivated by the fact that many applications in cell biology, such as wound healing, cancer invasion, and development, often involve tissues that are densely packed with cells where cell-to-cell contact and crowding effects can be important. To describe these kinds of high-cell-density problems using a velocity-jump process we introduce three different classes of crowding interactions into a one-dimensional model. Simulation data and averaging arguments lead to a suite of continuum descriptions of the interacting velocity-jump processes. We show that the resulting systems of hyperbolic partial differential equations predict the mean behavior of the stochastic simulations very well. PMID- 22304130 TI - Phase transition in an exactly solvable extinction model. AB - We introduce a model of biological evolution in which species evolve in response to biotic interactions and fluctuating environmental stress. The species may either become extinct or mutate to acquire a new fitness value when the effective stress level is greater than their individual fitness. The model exhibits a phase transition to a completely extinct phase as the environmental stress or the mutation rate is varied. We discuss the generic conditions for which this transition is continuous. The model is exactly solvable and the critical behavior is characterized by an unusual dynamic exponent z=1/3. Apart from predicting large-scale evolution, the model can be applied to understand the trends in the available fossil data. PMID- 22304131 TI - Curvature multiphase field model for phase separation on a membrane. AB - We propose a model to describe the physical mechanisms by which chemical substances separate in the vicinity of a membrane. We assume that the adsorption of the different components of a complex liquid on a membrane is governed by interactions that couple them to the spontaneous curvature of the membrane. This problem is relevant to many fields in science, as cell constriction and division, micelles with cosurfactants, holometamorphosis, and morphogenesis in general. PMID- 22304132 TI - Analytical behavior of the fourth and fifth virial coefficients of a hard-sphere mixture. AB - This paper focus on the study of the composition-dependent fourth and fifth virial coefficient of a hard-sphere binary mixture, namely, B(4)(s) and B(5)(s). On one side, the analytical expression of B(4)(s) is revised. In particular, I analyzed the composition-independent term B(4)[1](s) included in B(4)(s) and found a simplified form of its exact expression, which has the advantage over that previously published of highlighting the geometric properties of this term. On the other side, using a geometrical approach, I found a set of nonanalytic points of B(4)(s) and B(5)(s) as functions of s by analyzing each of their composition-independent terms. PMID- 22304133 TI - Brownian colloidal particles: Ito, Stratonovich, or a different stochastic interpretation. AB - Recent experiments on Brownian colloidal particles have been studied theoretically in terms of overdamped Langevin equations with multiplicative white noise using an unconventional stochastic interpretation. Complementary numerical simulations of the same system are well described using the conventional Stratonovich interpretation. Here we address this dichotomy from a more generic starting point: the underdamped Langevin equation and its corresponding Fokker Planck equation. PMID- 22304134 TI - Viscosity of methane to 6 GPa and 673 K. AB - A rolling-sphere technique has been used to measure shear viscosities of (supercritical) fluid methane in a diamond-anvil cell between temperatures of 294 and 673 K, up to a pressure of 6 GPa. A correlation between a reduced viscosity and reduced residual entropy is shown to give a good account of much of the extant data, both from this study and the literature. PMID- 22304135 TI - High-precision synthetic computed tomography of reconstructed porous media. AB - Multiscale simulation of transport in disordered and porous media requires microstructures covering several decades in length scale. X-ray and synchrotron computed tomography are presently unable to resolve more than one decade of geometric detail. Recent advances in pore scale modeling [Biswal, Held, Khanna, Wang, and Hilfer, Phys. Rev. E 80, 041301 (2009)] provide strongly correlated microstructures with several decades in microstructural detail. A carefully calibrated microstructure model for Fontainebleau sandstone has been discretized into a suite of three-dimensional microstructures with resolutions from roughly 128 MUm down to roughly 500 nm. At the highest resolution the three-dimensional image consists of 32768^{3}=35184372088832 discrete cubic volume elements with gray values between 0 and 216. To the best of our knowledge, this synthetic image is the largest computed tomogram of a porous medium available at present. PMID- 22304136 TI - Conductivity anisotropy of assembled and oriented carbon nanotubes. AB - An assembly of packed and oriented rodlike particles exhibit anisotropic physical properties. We investigate in the present work the anisotropic conductivity of films made of intrinsically conducting rods. These films are obtained from more or less ordered carbon nanotube liquid crystals. Their orientational order parameter is measured by polarized Raman spectroscopy. A relationship between the anisotropy of surface conductivity and orientational order parameter is determined. The experimental results are accounted for by a model that takes into account the number of intertube contacts and density of conductive pathways in different directions, as introduced by J. Fischer et al. for magnetically aligned nanotubes. We find that a good agreement, without any fitting parameter, of the proposed model and experiments is obtained when we consider a two-dimensional (2D) Gaussian distribution of the nanotube orientation. The conductivities parallel and perpendicular to the nematic director differ by almost an order of magnitude. This anisotropy is much greater than that of conventional dielectric liquid crystals, where the behavior is governed by the mobility anisotropy of ionic current carriers. The present results do not depend on the intrinsic properties of the nanotubes and are expected to be relevant for other assemblies of conducting rodlike particles, such as metallic or semi-conducting nanowires and ribbons. PMID- 22304137 TI - Detection and prediction of the onset of human ventricular fibrillation: an approach based on complex network theory. AB - Ventricular fibrillation is a life-threatening cardiac arrhythmia which deserves quick and reliable detection as well as prediction from human electrocardiogram time series. We constructed networks of human ventricular time series with the visibility graph approach to study the network subgraph phenomenon and motif ranks. Our results show that different dominant motifs exist as an effective indicator in distinguishing ventricular fibrillations from normal sinus rhythms of a subject. We verify the reliability of our findings in a large database with different time lengths and sampling frequencies, and design an onset predictor of ventricular fibrillations with reliable verifications. PMID- 22304138 TI - Length-dependent dynamics of microtubules. AB - Certain regulatory proteins influence the polymerization dynamics of microtubules by inducing catastrophe with a rate that depends on the microtubule length. Using a discrete formulation, here we show that, for a catastrophe rate proportional to the microtubule length, the steady-state probability distributions of length decay much faster with length than an exponential decay as seen in the absence of these proteins. PMID- 22304139 TI - Stochastic binary modeling of cells in continuous time as an alternative to biochemical reaction equations. AB - We have developed a coarse-grained formulation for modeling the dynamic behavior of cells quantitatively, based on stochasticity and heterogeneity, rather than on biochemical reactions. We treat each reaction as a continuous-time stochastic process, while reducing each biochemical quantity to a binary value at the level of individual cells. The system can be analytically represented by a finite set of ordinary linear differential equations, which provides a continuous time course prediction of each molecular state. Here we introduce our formalism and demonstrate it with several examples. PMID- 22304140 TI - Stiffness and strength of suture joints in nature. AB - Suture joints are remarkable mechanical structures found throughout nature composed of compliant interlocking seams connecting stiffer components. This study investigates the underlying mechanisms and the role of geometry governing the unique mechanical behavior of suture joints. Analytical and numerical composite models are formulated for two suture geometries characterized by a single repeating wavelength (e.g., triangular and rectangular). Stiffness, strength, and local stress distributions are predicted to assess variations in deformation and failure mechanisms. A unique homogeneous stress field is observed throughout both the skeletal and interfacial components of the triangular geometry, thus providing advantages in load transmission, weight, stiffness, strength, energy absorption, and fatigue over the rectangular geometry. The results obtained have relevance to biomimetic design and optimization, suture growth and fusion, and evolutionary phenotype diversity. PMID- 22304141 TI - Synchronization waves in geometric networks. AB - We report synchronization of networked excitable nodes embedded in a metric space, where the connectivity properties are mostly determined by the distance between units. Such a high clustered structure, combined with the lack of long range connections, prevents full synchronization and yields instead the emergence of synchronization waves. We show that this regime is optimal for information transmission through the system, as it enhances the options of reconstructing the topology from the dynamics. Measurements of topological and functional centralities reveal that the wave-synchronization state allows detection of the most structurally relevant nodes from a single observation of the dynamics, without any a priori information on the model equations ruling the evolution of the ensemble. PMID- 22304142 TI - Paradoxical transitions to instabilities in hydromagnetic Couette-Taylor flows. AB - By methods of modern spectral analysis, we rigorously find distributions of eigenvalues of linearized operators associated with an ideal hydromagnetic Couette-Taylor flow. The transition to instability in the limit of a vanishing magnetic field has a discontinuous change compared to the Rayleigh stability criterion for hydrodynamical flows, which is known as the Velikhov-Chandrasekhar paradox. PMID- 22304143 TI - Strong influence of geometrical heterogeneity on drainage in porous media. AB - We present an experimental study of drainage in two-dimensional porous media exhibiting bimodal pore size distributions. The role of the pore size heterogeneity is investigated by measuring separately the desaturation curves of the two pore populations. The displaced wetting fluid remains trapped in small pores at low capillary numbers and is swept only above a critical capillary number proportional to the permeability of the big pores network. Based on this observation, we derive a simple criterion for phase trapping based on the balance of viscous to capillary forces. Numerical implementation of this theory in a pore network model quantitatively fits our experimental results. This combination of approaches demonstrates quantitatively the influence of geometrical heterogeneities on drainage in porous media. PMID- 22304144 TI - Scale-free texture of the fast solar wind. AB - The higher-order statistics of magnetic field magnitude fluctuations in the fast quiet solar wind are quantified systematically, scale by scale. We find a single global non-Gaussian scale-free behavior from minutes to over 5 h. This spans the signature of an inertial range of magnetohydrodynamic turbulence and a ~1/f range in magnetic field components. This global scaling in field magnitude fluctuations is an intrinsic component of the underlying texture of the solar wind and puts a strong constraint on any theory of solar corona and the heliosphere. Intriguingly, the magnetic field and velocity components show scale-dependent dynamic alignment outside of the inertial range. PMID- 22304145 TI - Angular momentum flux of nonparaxial acoustic vortex beams and torques on axisymmetric objects. AB - An acoustic vortex in an inviscid fluid and its radiation torque on an axisymmetric absorbing object are analyzed beyond the paraxial approximation to clarify an analogy with an optical vortex. The angular momentum flux density tensor from the conservation of angular momentum is used as an efficient description of the transport of angular momentum. Analysis of a monochromatic nonparaxial acoustic vortex beam indicates that the local ratio of the axial (or radial) flux density of axial angular momentum to the axial (or radial) flux density of energy is exactly equal to the ratio of the beam's topological charge l to the acoustic frequency omega. The axial radiation torque exerted by the beam on an axisymmetric object centered on the beam's axis due to the transfer of angular momentum is proportional to the power absorbed by the object with a factor l/omega, which can be understood as a result of phonon absorption from the beam. Depending on the vortex's helicity, the torque is parallel or antiparallel to the beam's axis. PMID- 22304146 TI - Bending waves in crumpled sheets. AB - Crumpled paper has recently emerged as a model for disordered media. Here we use wave propagation to probe aluminum foils crumpled into balls made by hand or into cylinders obtained by confinement in a container. Surprisingly, the raw dispersion relations appear to differ from sample to sample. They correspond to bending waves that follow an effective path that is shorter than the distance between the input and output points. This can be interpreted in terms of two modes of propagation: slow bending waves and a fast mode whose possible origin is discussed. In addition, the effective paths behave differently in spheres and in cylinders. These results enable the characterization of the sample structure and point toward the geometric rigidity of the configurations. PMID- 22304147 TI - Ultrawide phononic band gap for combined in-plane and out-of-plane waves. AB - We consider two-dimensional phononic crystals formed from silicon and voids, and present optimized unit-cell designs for (1) out-of-plane, (2) in-plane, and (3) combined out-of-plane and in-plane elastic wave propagation. To feasibly search through an excessively large design space (~10(40) possible realizations) we develop a specialized genetic algorithm and utilize it in conjunction with the reduced Bloch mode expansion method for fast band-structure calculations. Focusing on high-symmetry plain-strain square lattices, we report unit-cell designs exhibiting record values of normalized band-gap size for all three categories. For the case of combined polarizations, we reveal a design with a normalized band-gap size exceeding 60%. PMID- 22304148 TI - Convergence for the Wang-Landau density of states. AB - The Wang-Landau method of estimating the density of states g(E) has become a powerful tool in statistical mechanics. Here it is shown that the distribution of random walkers sampled using an estimated density of states can always be used to improve the estimate. Specifically, this can be done without resorting to an auxiliary modification factor f, which previously has been used to find g(E) self consistently through a procedure that reduces f incrementally toward unity. This straightforward approach is validated for multiple, independent random walkers. PMID- 22304149 TI - Strategy of competition between two groups based on an inflexible contrarian opinion model. AB - We introduce an inflexible contrarian opinion (ICO) model in which a fraction p of inflexible contrarians within a group holds a strong opinion opposite to the opinion held by the rest of the group. At the initial stage, stable clusters of two opinions, A and B, exist. Then we introduce inflexible contrarians which hold a strong B opinion into the opinion A group. Through their interactions, the inflexible contrarians are able to decrease the size of the largest A opinion cluster and even destroy it. We see this kind of method in operation, e.g., when companies send free new products to potential customers in order to convince them to adopt their products and influence others to buy them. We study the ICO model, using two different strategies, on both Erdos-Renyi and scale-free networks. In strategy I, the inflexible contrarians are positioned at random. In strategy II, the inflexible contrarians are chosen to be the highest-degree nodes. We find that for both strategies the size of the largest A cluster decreases to 0 as p increases as in a phase transition. At a critical threshold value, p(c), the system undergoes a second-order phase transition that belongs to the same universality class of mean-field percolation. We find that even for an Erdos Renyi type model, where the degrees of the nodes are not so distinct, strategy II is significantly more effective in reducing the size of the largest A opinion cluster and, at very small values of p, the largest A opinion cluster is destroyed. PMID- 22304150 TI - Quasistationary simulations of the contact process on quenched networks. AB - We present high-accuracy quasistationary (QS) simulations of the contact process in quenched networks, built using the configuration model with both structural and natural cutoffs. The critical behavior is analyzed in the framework of the anomalous finite-size scaling which was recently shown to hold for the contact process on annealed networks. It turns out that the quenched topology does not qualitatively change the critical behavior, leading only (as expected) to a shift of the transition point. The anomalous finite-size scaling holds with exactly the same exponents of the annealed case, so we can conclude that heterogeneous mean field theory works for the contact process on quenched networks, at odds with previous claims. Interestingly, topological correlations induced by the presence of the natural cutoff do not alter the picture. PMID- 22304151 TI - Inertia in strategy switching transforms the strategy evolution. AB - A recent experimental study [Traulsen et al., Proc. Natl. Acad. Sci. 107, 2962 (2010)] shows that human strategy updating involves both direct payoff comparison and the cost of switching strategy, which is equivalent to inertia. However, it remains largely unclear how such a predisposed inertia affects 2 * 2 games in a well-mixed population of finite size. To address this issue, the "inertia bonus" (strategy switching cost) is added to the learner payoff in the Fermi process. We find how inertia quantitatively shapes the stationary distribution and that stochastic stability under inertia exhibits three regimes, with each covering seven regions in the plane spanned by two inertia parameters. We also obtain the extended "1/3" rule with inertia and the speed criterion with inertia; these two findings hold for a population above two. We illustrate the above results in the framework of the Prisoner's Dilemma game. As inertia varies, two intriguing stationary distributions emerge: the probability of coexistence state is maximized, or those of two full states are simultaneously peaked. Our results may provide useful insights into how the inertia of changing status quo acts on the strategy evolution and, in particular, the evolution of cooperation. PMID- 22304152 TI - Emerging properties of financial time series in the "Game of Life". AB - We explore the spatial complexity of Conway's "Game of Life," a prototypical cellular automaton by means of a geometrical procedure generating a two dimensional random walk from a bidimensional lattice with periodical boundaries. The one-dimensional projection of this process is analyzed and it turns out that some of its statistical properties resemble the so-called stylized facts observed in financial time series. The scope and meaning of this result are discussed from the viewpoint of complex systems. In particular, we stress how the supposed peculiarities of financial time series are, often, overrated in their importance. PMID- 22304153 TI - Modeling asset price processes based on mean-field framework. AB - We propose a model of the dynamics of financial assets based on the mean-field framework. This framework allows us to construct a model which includes the interaction among the financial assets reflecting the market structure. Our study is on the cutting edge in the sense of a microscopic approach to modeling the financial market. To demonstrate the effectiveness of our model concretely, we provide a case study, which is the pricing problem of the European call option with short-time memory noise. PMID- 22304154 TI - Asymptotic analysis of the stochastic block model for modular networks and its algorithmic applications. AB - In this paper we extend our previous work on the stochastic block model, a commonly used generative model for social and biological networks, and the problem of inferring functional groups or communities from the topology of the network. We use the cavity method of statistical physics to obtain an asymptotically exact analysis of the phase diagram. We describe in detail properties of the detectability-undetectability phase transition and the easy hard phase transition for the community detection problem. Our analysis translates naturally into a belief propagation algorithm for inferring the group memberships of the nodes in an optimal way, i.e., that maximizes the overlap with the underlying group memberships, and learning the underlying parameters of the block model. Finally, we apply the algorithm to two examples of real-world networks and discuss its performance. PMID- 22304155 TI - Effect of the nature of randomness on quenching dynamics of the Ising model on complex networks. AB - Randomness is known to affect the dynamical behavior of many systems to a large extent. In this paper we investigate how the nature of randomness affects the dynamics in a zero-temperature quench of the Ising model on two types of random networks. In both networks, which are embedded in a one-dimensional space, the first-neighbor connections exist and the average degree is 4 per node. In random model A the second-neighbor connections are rewired with a probability p, while in random model B additional connections between neighbors at a Euclidean distance l(l > 1) are introduced with a probability P(l) proportionally l( alpha). We find that for both models, the dynamics leads to freezing such that the system gets locked in a disordered state. The point at which the disorder of the nonequilibrium steady state is maximum is located. The behavior of dynamical quantities such as residual energy, order parameter, and persistence are discussed and compared. Overall, the behavior of physical quantities are similar, although subtle differences are observed due to the difference in the nature of randomness. PMID- 22304156 TI - Large-scale curvature of networks. AB - Understanding key structural properties of large-scale networks is crucial for analyzing and optimizing their performance and improving their reliability and security. Here, through an analysis of a collection of data networks across the globe as measured and documented by previous researchers, we show that communications networks at the Internet protocol (IP) layer possess global negative curvature. We show that negative curvature is independent of previously studied network properties, and that it has a major impact on core congestion: the load at the core of a finite negatively curved network with N nodes scales as N(2), as compared to N(1.5) for a generic finite flat network. PMID- 22304157 TI - Self-organized network of phase oscillators coupled by activity-dependent interactions. AB - We investigate a network of coupled phase oscillators whose interactions evolve dynamically depending on the relative phases between the oscillators. We found that this coevolving dynamical system robustly yields three basic states of collective behavior with their self-organized interactions. The first is the two cluster state, in which the oscillators are organized into two synchronized groups. The second is the coherent state, in which the oscillators are arranged sequentially in time. The third is the chaotic state, in which the relative phases between oscillators and their coupling weights are chaotically shuffled. Furthermore, we demonstrate that self-assembled multiclusters can be designed by controlling the weight dynamics. Note that the phase patterns of the oscillators and the weighted network of interactions between them are simultaneously organized through this coevolving dynamics. We expect that these results will provide new insight into self-assembly mechanisms by which the collective behavior of a rhythmic system emerges as a result of the dynamics of adaptive interactions. PMID- 22304158 TI - Scaling properties and universality of first-passage-time probabilities in financial markets. AB - Financial markets provide an ideal frame for the study of crossing or first passage time events of non-Gaussian correlated dynamics, mainly because large data sets are available. Tick-by-tick data of six futures markets are herein considered, resulting in fat-tailed first-passage time probabilities. The scaling of the return with its standard deviation collapses the probabilities of all markets examined--and also for different time horizons--into single curves, suggesting that first-passage statistics is market independent (at least for high frequency data). On the other hand, a very closely related quantity, the survival probability, shows, away from the center and tails of the distribution, a hyperbolic t(-1/2) decay typical of a Markovian dynamics, albeit the existence of memory in markets. Modifications of the Weibull and Student distributions are good candidates for the phenomenological description of first-passage time properties under certain regimes. The scaling strategies shown may be useful for risk control and algorithmic trading. PMID- 22304159 TI - Random sequential renormalization and agglomerative percolation in networks: application to Erdos-Renyi and scale-free graphs. AB - We study the statistical behavior under random sequential renormalization (RSR) of several network models including Erdos-Renyi (ER) graphs, scale-free networks, and an annealed model related to ER graphs. In RSR the network is locally coarse grained by choosing at each renormalization step a node at random and joining it to all its neighbors. Compared to previous (quasi-)parallel renormalization methods [Song et al., Nature (London) 433, 392 (2005)], RSR allows a more fine grained analysis of the renormalization group (RG) flow and unravels new features that were not discussed in the previous analyses. In particular, we find that all networks exhibit a second-order transition in their RG flow. This phase transition is associated with the emergence of a giant hub and can be viewed as a new variant of percolation, called agglomerative percolation. We claim that this transition exists also in previous graph renormalization schemes and explains some of the scaling behavior seen there. For critical trees it happens as N/N(0) > 0 in the limit of large systems (where N(0) is the initial size of the graph and N its size at a given RSR step). In contrast, it happens at finite N/N(0) in sparse ER graphs and in the annealed model, while it happens for N/N(0) -> 1 on scale-free networks. Critical exponents seem to depend on the type of the graph but not on the average degree and obey usual scaling relations for percolation phenomena. For the annealed model they agree with the exponents obtained from a mean-field theory. At late times, the networks exhibit a starlike structure in agreement with the results of Radicchi et al. [Phys. Rev. Lett. 101, 148701 (2008)]. While degree distributions are of main interest when regarding the scheme as network renormalization, mass distributions (which are more relevant when considering "supernodes" as clusters) are much easier to study using the fast Newman-Ziff algorithm for percolation, allowing us to obtain very high statistics. PMID- 22304160 TI - Explosive site percolation and finite-size hysteresis. AB - We report the critical point for site percolation for the "explosive" type for two-dimensional square lattices using Monte Carlo simulations and compare it to the classical well-known percolation. We use similar algorithms as have been recently reported for bond percolation and networks. We calculate the explosive site percolation threshold as p(c) = 0.695 and we find evidence that explosive site percolation surprisingly may belong to a different universality class than bond percolation on lattices, providing that the transitions (a) are continuous and (b) obey the conventional finite size scaling forms. Finally, we study and compare the direct and reverse processes, showing that while the reverse process is different from the direct process for finite size systems, the two cases become equivalent in the thermodynamic limit of large L. PMID- 22304161 TI - Entropy rate of nonequilibrium growing networks. AB - New entropy measures have been recently introduced for the quantification of the complexity of networks. Most of these entropy measures apply to static networks or to dynamical processes defined on static complex networks. In this paper we define the entropy rate of growing network models. This entropy rate quantifies how many labeled networks are typically generated by the growing network models. We analytically evaluate the difference between the entropy rate of growing tree network models and the entropy of tree networks that have the same asymptotic degree distribution. We find that the growing networks with linear preferential attachment generated by dynamical models are exponentially less than the static networks with the same degree distribution for a large variety of relevant growing network models. We study the entropy rate for growing network models showing structural phase transitions including models with nonlinear preferential attachment. Finally, we bring numerical evidence that the entropy rate above and below the structural phase transitions follows a different scaling with the network size. PMID- 22304162 TI - Hurst exponents for short time series. AB - A concept called balanced estimator of diffusion entropy is proposed to detect quantitatively scalings in short time series. The effectiveness is verified by detecting successfully scaling properties for a large number of artificial fractional Brownian motions. Calculations show that this method can give reliable scalings for short time series with length ~10(2). It is also used to detect scalings in the Shanghai Stock Index, five stock catalogs, and a total of 134 stocks collected from the Shanghai Stock Exchange Market. The scaling exponent for each catalog is significantly larger compared with that for the stocks included in the catalog. Selecting a window with size 650, the evolution of scaling for the Shanghai Stock Index is obtained by the window's sliding along the series. Global patterns in the evolutionary process are captured from the smoothed evolutionary curve. By comparing the patterns with the important event list in the history of the considered stock market, the evolution of scaling is matched with the stock index series. We can find that the important events fit very well with global transitions of the scaling behaviors. PMID- 22304163 TI - Effects of punishment in a mobile population playing the prisoner's dilemma game. AB - We deal with a system of prisoner's dilemma players undergoing continuous motion in a two-dimensional plane. In contrast to previous work, we introduce altruistic punishment after the game. We find punishing only a few of the cooperator defector interactions is enough to lead the system to a cooperative state in environments where otherwise defection would take over the population. This happens even with soft nonsocial punishment (where both cooperators and defectors punish other players, a behavior observed in many human populations). For high enough mobilities or temptations to defect, low rates of social punishment can no longer avoid the breakdown of cooperation. PMID- 22304164 TI - Percolation in interdependent and interconnected networks: abrupt change from second- to first-order transitions. AB - Robustness of two coupled networks systems has been studied separately only for dependency coupling [Buldyrev et al., Nature (London) 464, 1025 (2010)] and only for connectivity coupling [Leicht and D'Souza, e-print arXiv:0907.0894]. Here we study, using a percolation approach, a more realistic coupled networks system where both interdependent and interconnected links exist. We find rich and unusual phase-transition phenomena including hybrid transition of mixed first and second order, i.e., discontinuities like in a first-order transition of the giant component followed by a continuous decrease to zero like in a second-order transition. Moreover, we find unusual discontinuous changes from second-order to first-order transition as a function of the dependency coupling between the two networks. PMID- 22304165 TI - Clustering drives assortativity and community structure in ensembles of networks. AB - Clustering, assortativity, and communities are key features of complex networks. We probe dependencies between these features and find that ensembles of networks with high clustering display both high assortativity by degree and prominent community structure, while ensembles with high assortativity show much less enhancement of the clustering or community structure. Further, clustering can amplify a small homophilic bias for trait assortativity in network ensembles. This marked asymmetry suggests that transitivity could play a larger role than homophily in determining the structure of many complex networks. PMID- 22304166 TI - Statistical tests for power-law cross-correlated processes. AB - For stationary time series, the cross-covariance and the cross-correlation as functions of time lag n serve to quantify the similarity of two time series. The latter measure is also used to assess whether the cross-correlations are statistically significant. For nonstationary time series, the analogous measures are detrended cross-correlations analysis (DCCA) and the recently proposed detrended cross-correlation coefficient, rho(DCCA)(T,n), where T is the total length of the time series and n the window size. For rho(DCCA)(T,n), we numerically calculated the Cauchy inequality -1 <= rho(DCCA)(T,n) <= 1. Here we derive -1 <= rho DCCA)(T,n) <= 1 for a standard variance-covariance approach and for a detrending approach. For overlapping windows, we find the range of rho(DCCA) within which the cross-correlations become statistically significant. For overlapping windows we numerically determine-and for nonoverlapping windows we derive--that the standard deviation of rho(DCCA)(T,n) tends with increasing T to 1/T. Using rho(DCCA)(T,n) we show that the Chinese financial market's tendency to follow the U.S. market is extremely weak. We also propose an additional statistical test that can be used to quantify the existence of cross-correlations between two power-law correlated time series. PMID- 22304167 TI - Numerical study of the correspondence between the dissipative and fixed-energy Abelian sandpile models. AB - We consider the Abelian sandpile model (ASM) on the square lattice with a single dissipative site (sink). Particles are added one by one per unit time at random sites and the resulting density of particles is calculated as a function of time. We observe different scenarios of evolution depending on the value of initial uniform density (height) h(0). During the first stage of the evolution, the density of particles increases linearly. Reaching a critical density rho(c)(h(0)), the system changes its behavior and relaxes exponentially to the stationary state of the ASM with density rho(s). Considering initial heights -1 <= h(0) <= 4, we observe a dramatic decrease of the difference rho(c)(h(0)) - rho(s) when h(0) is zero or negative. In parallel with the ASM, we consider the conservative fixed energy sandpile (FES). The extensive Monte Carlo simulations show that the threshold density rho(th)(h(0)) of the FES converges rapidly to rho(s) for h(0) < 1. PMID- 22304168 TI - Tweedie convergence: a mathematical basis for Taylor's power law, 1/f noise, and multifractality. AB - Plants and animals of a given species tend to cluster within their habitats in accordance with a power function between their mean density and the variance. This relationship, Taylor's power law, has been variously explained by ecologists in terms of animal behavior, interspecies interactions, demographic effects, etc., all without consensus. Taylor's law also manifests within a wide range of other biological and physical processes, sometimes being referred to as fluctuation scaling and attributed to effects of the second law of thermodynamics. 1/f noise refers to power spectra that have an approximately inverse dependence on frequency. Like Taylor's law these spectra manifest from a wide range of biological and physical processes, without general agreement as to cause. One contemporary paradigm for 1/f noise has been based on the physics of self-organized criticality. We show here that Taylor's law (when derived from sequential data using the method of expanding bins) implies 1/f noise, and that both phenomena can be explained by a central limit-like effect that establishes the class of Tweedie exponential dispersion models as foci for this convergence. These Tweedie models are probabilistic models characterized by closure under additive and reproductive convolution as well as under scale transformation, and consequently manifest a variance to mean power function. We provide examples of Taylor's law, 1/f noise, and multifractality within the eigenvalue deviations of the Gaussian unitary and orthogonal ensembles, and show that these deviations conform to the Tweedie compound Poisson distribution. The Tweedie convergence theorem provides a unified mathematical explanation for the origin of Taylor's law and 1/f noise applicable to a wide range of biological, physical, and mathematical processes, as well as to multifractality. PMID- 22304169 TI - Pressure solution as origin of the humid creep of a mineral material. AB - The significant enhancement of the creep of plasterboard by a humid environment is well known in the building industry. But despite its strong impact on the material durability, its origin remains unexplained. We present here experimental evidence that the creep of wet set plaster is driven by the dissolution kinetics of gypsum, its major component, in intercrystalline water layers. Linking this surface molecular behavior to a macroscopic mechanical property has been made possible by the establishment, using holographic interferometry, of an accurate method of convection-free dissolution measurement, and by the possibility of tuning the dissolution kinetics of the material by the use of additives. Although it is well known in geological contexts, this dissolution-creep correlation had not yet been observed outside this field. It enables one to propose pressure solution as the mechanism of the wet creep of set plaster and sheds light on the humid creep of polycrystalline mineral materials. PMID- 22304170 TI - Limits of modularity maximization in community detection. AB - Modularity maximization is the most popular technique for the detection of community structure in graphs. The resolution limit of the method is supposedly solvable with the introduction of modified versions of the measure, with tunable resolution parameters. We show that multiresolution modularity suffers from two opposite coexisting problems: the tendency to merge small subgraphs, which dominates when the resolution is low; the tendency to split large subgraphs, which dominates when the resolution is high. In benchmark networks with heterogeneous distributions of cluster sizes, the simultaneous elimination of both biases is not possible and multiresolution modularity is not capable to recover the planted community structure, not even when it is pronounced and easily detectable by other methods, for any value of the resolution parameter. This holds for other multiresolution techniques and it is likely to be a general problem of methods based on global optimization. PMID- 22304171 TI - Monofractal and multifractal analysis of the spatial distribution of earthquakes in the central zone of Chile. AB - Statistical and fractal properties of the spatial distribution of earthquakes in the central zone of Chile are studied. In particular, data are shown to behave according to the well-known Gutenberg-Richter law. The fractal structure is evident for epicenters, not for hypocenters. The multifractal spectrum is also determined, both for the spatial distribution of epicenters and hypocenters. For negative values of the index of multifractal measure q, the multifractal spectrum, which usually cannot be reliably found from data, is calculated from a generalized Cantor-set model, which fits the multifractal spectrum for q > 0, a technique which has been previously applied for analysis of solar wind data. PMID- 22304172 TI - Spectral behavior of contractive noise. AB - We study the behavior of the spectra corresponding to quantum systems subjected to a contractive noise, i.e., the environment reduces the accessible phase space of the system, but the total probability is conserved. We find that the number of long-lived resonances grows as a power law in h, but surprisingly there is no relationship between the exponent of this power law and the fractal dimension of the corresponding classical attractor. This is in disagreement with the predictions of the fractal Weyl law which has been established for open systems, where the probability is lost under the effect of a projective opening. PMID- 22304173 TI - Engineering the synchronization of neuron action potentials using global time delayed feedback stimulation. AB - We experimentally demonstrate the use of continuous, time-delayed, feedback stimulation for controlling the synchronization of neuron action potentials. Phase-based models were experimentally constructed from a single synaptically isolated cultured hippocampal neuron. These models were used to determine the stimulation parameters necessary to produce the desired synchronization behavior in the action potentials of a pair of neurons coupled through a global time delayed interaction. Measurements made using a dynamic clamp system confirm the generation of the synchronized states predicted by the experimentally constructed phase model. This model was then utilized to extrapolate the feedback stimulation parameters necessary to disrupt the action potential synchronization of a large population of globally interacting neurons. PMID- 22304174 TI - Existence and stability of traveling-wave states in a ring of nonlocally coupled phase oscillators with propagation delays. AB - We investigate the existence and stability of traveling-wave solutions in a continuum field of nonlocally coupled identical phase oscillators with distance dependent propagation delays. A comprehensive stability diagram in the parametric space of the system is presented that shows a rich structure of multistable regions and illuminates the relative influences of time delay, the nonlocality parameter and the intrinsic oscillator frequency on the dynamics of these states. A decrease in the intrinsic oscillator frequency leads to a break-up of the stability domains of the traveling waves into disconnected regions in the parametric space. These regions exhibit a tongue structure for high connectivity, whereas they submerge into the stable region of the synchronous state for low connectivity. One finding is the existence of forbidden regions in the parametric space where no phase-locked solutions are possible. We also discover a new class of nonstationary breather states for this model system that are characterized by periodic oscillations of the complex order parameter. PMID- 22304175 TI - Coexistence of exponentially many chaotic spin-glass attractors. AB - A chaotic network of size N with delayed interactions which resembles a pseudoinverse associative memory neural network is investigated. For a load alpha = P/N < 1, where P stands for the number of stored patterns, the chaotic network functions as an associative memory of 2P attractors with macroscopic basin of attractions which decrease with alpha. At finite alpha, a chaotic spin-glass phase exists, where the number of distinct chaotic attractors scales exponentially with N. Each attractor is characterized by a coexistence of chaotic behavior and freezing of each one of the N chaotic units or freezing with respect to the P patterns. Results are supported by large scale simulations of networks composed of Bernoulli map units and Mackey-Glass time delay differential equations. PMID- 22304176 TI - Efficient sampling avoids the exponential wall in classical simulations of fidelity. AB - We analyze the efficiency of available algorithms for the simulation of classical fidelity and show that their computational costs increase exponentially with the number of degrees of freedom. Then we present an algorithm for which the number of trajectories needed for convergence is independent of the system's dimensionality and show that, within a continuous family of algorithms, this algorithm is the only one with this property. Simultaneously we propose a general analytical approach to estimate efficiency of trajectory-based methods and suggest how to use it to accelerate calculations of other classical correlation functions. Converged numerical results are provided for systems with phase space volume 2^{1700} times larger than the volume of the initial state. PMID- 22304177 TI - Delay-enhanced coherent chaotic oscillations in networks with large disorders. AB - We study the effect of coupling delay in a regular network with a ring topology and in a more complex network with an all-to-all (global) topology in the presence of impurities (disorder). We find that the coupling delay is capable of inducing phase-coherent chaotic oscillations in both types of networks, thereby enhancing the spatiotemporal complexity even in the presence of 50% of symmetric disorders of both fixed and random types. Furthermore, the coupling delay increases the robustness of the networks up to 70% of disorders, thereby preventing the network from acquiring periodic oscillations to foster disorder induced spatiotemporal order. We also confirm the enhancement of coherent chaotic oscillations using snapshots of the phases and values of the associated Kuramoto order parameter. We also explain a possible mechanism for the phenomenon of delay induced coherent chaotic oscillations despite the presence of large disorders and discuss its applications. PMID- 22304178 TI - Variational approximations to homoclinic snaking in continuous and discrete systems. AB - Localized structures appear in a wide variety of systems, arising from a pinning mechanism due to the presence of a small-scale pattern or an imposed grid. When there is a separation of length scales, the width of the pinning region is exponentially small and beyond the reach of standard asymptotic methods. We show how this behavior can be obtained using a variational method, for two systems. In the case of the quadratic-cubic Swift-Hohenberg equation, this gives results that are in agreement with recent work using exponential asymptotics. In addition, the method is applied to a discrete system with cubic-quintic nonlinearity, giving results that agree well with numerical simulations. PMID- 22304179 TI - Control of delay-induced oscillation death by coupling phase in coupled oscillators. AB - A coupling phase is deemed to be crucial in stabilizing behavior in nonlinear systems. In this paper, we study how the coupling phase influences the delay induced oscillation death (OD) in coupled oscillators. The OD boundaries are identified analytically even in the presence of the coupling phase. We find that OD only occurs for a coupling phase belonging to a certain interval. The optimal coupling phase, under which the largest OD island forms, is characterized well by a power law scaling with respect to the frequency. The coupling phase turns out to be a key parameter that determines a delay-induced OD. Furthermore, the controlling role of the coupling phase generally is proved to hold fairly for networked delay-coupled oscillators. PMID- 22304180 TI - Excitatory and inhibitory coupling in a one-dimensional array of Belousov Zhabotinsky micro-oscillators: theory. AB - We study numerically the behavior of one-dimensional arrays of aqueous droplets containing the oscillatory Belousov-Zhabotinsky reaction. Droplets are separated by an oil phase that allows coupling between neighboring droplets via two species: an inhibitor, Br(2), and an activator, HBrO(2). Excitatory coupling alone (through the activator) generates in-phase oscillations and/or "waves," while inhibitory coupling alone (through Br(2)) gives rise to antiphase oscillations, Turing patterns, and their combinations. The simultaneous presence of excitatory and inhibitory coupling leads to a large number of new spatiotemporal patterns, including some that exhibit very complex behavior. Analysis of a simple model allows us to simulate patterns resembling those observed experimentally under similar conditions and to elucidate the contributions of droplet and gap sizes, activator and inhibitor partition coefficients, and malonic acid concentration to the coupling strengths. PMID- 22304181 TI - Lyapunov statistics and mixing rates for intermittent systems. AB - We consider here a recent conjecture stating that correlation functions and tail probabilities of finite time Lyapunov exponents would have the same power law decay in weakly chaotic systems. We demonstrate that this conjecture fails for a generic class of maps of the Pomeau-Manneville type. We show further that, typically, the decay properties of such tail probabilities do not provide significant information on key aspects of weakly chaotic dynamics such as ergodicity and instability regimes. Our approaches are firmly based on rigorous results, particularly the Aaronson-Darling-Kac theorem, and are also confirmed by exhaustive numerical simulations. PMID- 22304182 TI - Chaos in the Hamiltonian mean-field model. AB - We study the dynamical properties of the canonical ordered phase of the Hamiltonian mean-field (HMF) model, in which N particles, globally coupled via pairwise attractive interactions, form a rotating cluster. Using a combination of numerical and analytical arguments, we first show that the largest Lyapunov exponent remains strictly positive in the infinite-size limit, converging to its asymptotic value with 1/lnN corrections. We then elucidate the scaling laws ruling the behavior of this asymptotic value in the critical region separating the ordered, clustered phase and the disordered phase present at high-energy densities. We also show that the full spectrum of Lyapunov exponents consists of a bulk component converging to the (zero) value taken by a test oscillator forced by the mean field, plus subextensive bands of O(ln N) exponents taking finite values. We finally investigate the robustness of these results by studying a "2D" extension of the HMF model where each particle is endowed with 4 degrees of freedom, thus allowing the emergence of chaos at the level of a single particle. Altogether, these results illustrate the subtle effects of global (or long-range) coupling and the importance of the order in which the infinite-time and infinite size limits are taken: For an infinite-size HMF system represented by the Vlasov equation, no chaos is present, while chaos exists and subsists for any finite system size. PMID- 22304183 TI - Type of spiral wave with trapped ions. AB - Pattern formation in ultracold quantum systems has recently received a great deal of attention. In this work, we investigate a two-dimensional model system simulating the dynamics of trapped ions. We find a spiral wave that is rigidly rotating, but with a peculiar core region in which adjacent ions oscillate in antiphase. The formation of this spiral wave is ascribed to the excitability previously reported by Lee and Cross. The breakup of the spiral wave is probed and, especially, an extraordinary scenario of the disappearance of the spiral wave, caused by spontaneous expansion of the antiphase core, is unveiled. PMID- 22304184 TI - Thin three-dimensional drops on a slowly oscillating substrate. AB - We examine the evolution of a liquid drop on an inclined substrate oscillating vertically. The drop is assumed thin, and the oscillations are assumed weak and slow (the latter makes the liquid's inertia and viscosity negligible, so the drop's shape is determined by a balance of surface tension, gravity, and vibration-induced inertial force). On the basis of these approximations, asymptotic expressions are derived for the mean velocities of two- (2D) and three dimensional (3D) drops. It is shown that, if the amplitude of the substrate's oscillations exceeds a certain threshold value, both 2D and 3D drops climb uphill. The two cases, however, exhibit different behaviors of the threshold amplitude of the oscillations on their frequency, in the low-frequency limit: to make 2D drops climb uphill, the oscillations must be much stronger than those in the 3D case. This difference is important, as the 2D behavior does not fit the existing experimental results. PMID- 22304185 TI - Degassing cascades in a shear-thinning viscoelastic fluid. AB - We report the experimental study of the degassing dynamics through a thin layer of shear-thinning viscoelastic fluid when a constant air flow is imposed at its bottom. The fluid is an aqueous solution of cetyltrimethylammonium bromide (CTAB) and sodium salicylate (NaSal). Over a large range of parameters, the air is periodically released through a series of successive bubbles, hereafter named cascades. Each cascade is followed by a continuous degassing, lasting for several seconds, corresponding to an open channel crossing the fluid layer. The periodicity between two cascades does not depend on the injected flow rate. Inside one cascade, the properties of the overpressure signal associated with the successive bubbles vary continuously. The pressure threshold above which the fluid starts flowing, fluid deformation and pressure drop due to degassing through the thin fluid layer can be simply described by a Maxwell model. PMID- 22304186 TI - Designing structured surfaces that repel fluid-borne particles. AB - Using computational modeling, we examine particle-laden flows along surfaces decorated with periodic arrays of tilted posts. We show that when high-aspect ratio posts are tilted against the flow direction, cross-stream circulatory secondary flows emerge. These circulatory flows enhance the net lift force acting on finite-sized particles transported by fluid, thereby repelling the particles from the wall and preventing their deposition. This hydrodynamic effect can potentially be used for designing antifouling and self-cleaning surfaces. PMID- 22304187 TI - Enhanced carbon dioxide adsorption through carbon nanoscrolls. AB - Over the last few years, significant efforts have been devoted to exploring the capabilities of carbon based structures for gas separation and filtration. In the present study the layering behavior of carbon dioxide transported through carbon nanoscrolls is examined through molecular dynamics simulations. The layering arrangements are investigated for carbon nanoscrolls with intralayer distances spanning from 4.2 to 8.3 A at temperature of 300 K and pressures ranging from 5 to 20 bars. Characteristic layering structures are developed around the internal and external surfaces of the nanoscroll for all the examined cases. It is shown that the number of layers, their relative strength, and the starting point of bifurcation phenomena vary as a function of the nanoscrolls' intralayer distance, scroll's core radius, CO2 density, and gas structure interactions. It is also shown that the number of carbon dioxide molecules adsorbed per scroll's carbon particles is a function of the scroll's surface-to-volume ratio and is maximized under certain structural configurations. PMID- 22304188 TI - Relaxation mechanisms of photoinduced periodic microstructures in ferrofluid layers. AB - We consider theoretically and numerically a periodic concentration grating induced in a layer of ferrofluid in the presence of the external magnetic field by nonuniform optical heating through photoabsorption. The stationary profiles of the periodic microstructures are governed by the equilibrium of the diffusive, thermodiffusive, and magnetic fluxes. The anisotropy of the diffusion coefficient and the magnetically driven microconvection contribute to the relaxation of these structures. The temperature-concentration coupling is shown to increase the initial effective diffusive relaxation rate by up to 50%. Microconvection dominates in the relaxation process even at small values of the control parameter and rapidly destroys the periodic part of the concentration grating. We describe this process in the weakly nonlinear regime by an approximate Galerkin model. PMID- 22304189 TI - Studying flow close to an interface by total internal reflection fluorescence cross-correlation spectroscopy: quantitative data analysis. AB - Total internal reflection fluorescence cross-correlation spectroscopy (TIR-FCCS) has recently [S. Yordanov et al., Optics Express 17, 21149 (2009)] been established as an experimental method to probe hydrodynamic flows near surfaces, on length scales of tens of nanometers. Its main advantage is that fluorescence occurs only for tracer particles close to the surface, thus resulting in high sensitivity. However, the measured correlation functions provide only rather indirect information about the flow parameters of interest, such as the shear rate and the slip length. In the present paper, we show how to combine detailed and fairly realistic theoretical modeling of the phenomena by Brownian dynamics simulations with accurate measurements of the correlation functions, in order to establish a quantitative method to retrieve the flow properties from the experiments. First, Brownian dynamics is used to sample highly accurate correlation functions for a fixed set of model parameters. Second, these parameters are varied systematically by means of an importance-sampling Monte Carlo procedure in order to fit the experiments. This provides the optimum parameter values together with their statistical error bars. The approach is well suited for massively parallel computers, which allows us to do the data analysis within moderate computing times. The method is applied to flow near a hydrophilic surface, where the slip length is observed to be smaller than 10nm, and, within the limitations of the experiments and the model, indistinguishable from zero. PMID- 22304190 TI - Interaction of two differently sized oscillating bubbles in a free field. AB - Most real life bubble dynamics applications involve multiple bubbles, for example, in cavitation erosion prevention, ultrasonic baths, underwater warfare, and medical applications involving microbubble contrast agents. Most scientific dealings with bubble-bubble interaction focus on two similarly sized bubbles. In this study, the interaction between two oscillating differently sized bubbles (generated in tap water) is studied using high speed photography. Four types of bubble behavior were observed, namely, jetting toward each other, jetting away from each other, bubble coalescence, and a behavior termed the "catapult" effect. In-phase bubbles jet toward each other, while out-of-phase bubbles jet away from each other. There exists a critical phase difference that separates the two regimes. The behavior of the bubbles is fully characterized by their dimensionless separation distance, their phase difference, and their size ratio. It is also found that for bubbles with large size difference, the smaller bubble behaves similarly to a single bubble oscillating near a free surface. PMID- 22304191 TI - Anisotropic shell model of turbulence. AB - An anisotropic shell model has been proposed for two-dimensional (2D) turbulence. It is similar to the 2D version of the Gledzer-Ohkitani-Yamada model but with the angular variable in wave-number space divided into three distinct directions representing structures elongated in different directions. In the case when the drive is isotropic the usual isotropic solution is recovered as the fixed point of this model. The Hasegawa-Mima limit of the model is considered in particular due to its relevance for 2D anisotropic systems such a quasigeostrophic and plasma turbulence. It is observed from this simple model that the anisotropy diminishes as a function of scale during the cascade process, and the maximum of the energy is not at the node that has maximum drive, but at a nearby node that is directly coupled to that one. PMID- 22304192 TI - Analysis of chaotic mixing in plugs moving in meandering microchannels. AB - Droplets moving in meandering microchannels can serve as a passive and robust strategy to produce chaotic mixing of species in droplet-based microfluidics. In this paper, a simplified theoretical model is proposed for plug-shaped droplets moving in meandering microchannels at Stokes flow. With this model to provide the velocity field, particle tracking, which requires a large computation time, is performed directly and easily without interpolation. With this convenience, a broad survey of the parameter space is carried out to investigate chaotic mixing in plugs, including the channel curvature, the Peclet number, the viscosity ratio, and the plug length. The results show that in order to achieve rapid mixing in plugs in meandering microchannels, a large curvature, a small Peclet number, a moderate viscosity ratio, and a moderate plug length are preferred. PMID- 22304193 TI - Characterization of acoustic droplet formation in a microfluidic flow-focusing device. AB - Local control of droplet formation with acoustic actuation in a microfluidic flow focusing device is investigated, and the effects of acoustic voltage, frequency, flow-rate ratio, fluid viscosity, and flow vorticity are characterized. Acoustic actuation is provided to affect droplet breakup in the squeezing regime by imposing periodic oscillation to the fluid-fluid interface and, therefore, a periodic change in its curvature at the cross-junction of the device. Time reduction is observed for the three key stages of droplet breakup in the squeezing regime: dispersed phase flow-front advancement into the orifice, pressure buildup upstream and within the orifice together with liquid inflation downstream, and finally the thinning and pinch-off of the liquid thread. It is found that acoustic actuation has less of an effect on droplet size for the continuous phase with a higher viscosity due to the restrained interfacial vibration under a high shear stress environment. Periodic velocity flow fields within the dispersed phase at different phases of one oscillation cycle are calculated based on the results from phase-averaged microresolution-particle image velocimetry (MUPIV). The oscillation paths for the points of maximum vorticities of phase-averaged velocity components are traced, which reveals that the motion is mainly along the y direction. PMID- 22304194 TI - Effect of molecular structure on liquid slip. AB - Slip behavior of three liquids with distinct molecular shapes--linear (hexadecane), branched (pentaerythritol tetra), and a chain of rings (polyphenylether)--is studied using molecular dynamics simulation and reduced order modeling. Slip at a liquid-solid interface is shown to be affected by the molecular structure of the liquid. A two-dimensional Frenkel-Kontorova model captures the fundamental structural features of the liquid molecules and gives insight into how molecules flex and slip along the surface. We formulate an approximation to the Peierls-Nabarro energy which incorporates both the position of liquid atoms relative to substrate atoms and molecular flexibility. We find that increased molecular flexibility can lead to reduced slip by allowing the liquid to conform epitaxially to the substrate with only a small energetic penalty. Liquid molecules which are less flexible can conform to the substrate only with greater expense of conformational energy, and so exhibit larger slip. PMID- 22304195 TI - Quantifying mixing in viscously unstable porous media flows. AB - Viscous fingering is a well-known hydrodynamic instability that sets in when a less viscous fluid displaces a more viscous fluid. When the two fluids are miscible, viscous fingering introduces disorder in the velocity field and exerts a fundamental control on the rate at which the fluids mix. Here we analyze the characteristic signature of the mixing process in viscously unstable flows, by means of high-resolution numerical simulations using a computational strategy that is stable for arbitrary viscosity ratios. We propose a reduced-order model of mixing, which, in the spirit of turbulence modeling and in contrast with previous approaches, recognizes the fundamental role played by the mechanical dissipation rate. The proposed model captures the nontrivial interplay between channeling and creation of interfacial area as a result of viscous fingering. PMID- 22304196 TI - Controlling fingering instabilities in nonflat Hele-Shaw geometries. AB - In analogy to the viscous fingering problem between parallel flat plates, injection-driven flow in nonflat (conical and spherical) Hele-Shaw cells gives rise to ramified interfacial structures. The multiple occurrences of fingertip splitting events makes the resulting pattern difficult to predict and to control. We calculate expressions for time-dependent injection rates that suppress the development of bifurcated shapes on curved confined environments. Implementation of these injection procedures leads to interfacial shapes with a robust n-fold symmetry. A weakly nonlinear approach is used to extract important analytical information about the influence of the geometric and topological features of the nonflat cells on the efficiency of the proposed fingering control processes. PMID- 22304197 TI - Inviscid helical magnetorotational instability in cylindrical Taylor-Couette flow. AB - This paper presents the analysis of axisymmetric helical magnetorotational instability (HMRI) in the inviscid limit, which is relevant for astrophysical conditions. The inductionless approximation defined by zero magnetic Prandtl number is adopted to distinguish the HMRI from the standard MRI in the cylindrical Taylor-Couette flow subject to a helical magnetic field. Using a Chebyshev collocation method convective and absolute instability thresholds are computed in terms of the Elsasser number for a fixed ratio of inner and outer radii lambda = 2 and various ratios of rotation rates and helicities of the magnetic field. It is found that the extension of self-sustained HMRI modes beyond the Rayleigh limit does not reach the astrophysically relevant Keplerian rotation profile not only in the narrow- but also in the finite-gap approximation. The Keppler limit can be attained only by the convective HMRI mode provided that the boundaries are perfectly conducting. However, this mode requires not only a permanent external excitation to be observable but also has a long axial wavelength, which is not compatible with limited thickness of astrophysical accretion disks. PMID- 22304198 TI - Stochastic and deterministic motion of a laminar-turbulent front in a spanwisely extended Couette flow. AB - We investigate numerically the dynamics of a laminar-turbulent interface in a spanwisely extended and streamwisely minimal plane Couette flow. The chosen geometry allows one to suppress the large-scale secondary flow and to focus on the nucleation of streaks near the interface. It is shown that the resulting spanwise motion of the interface is essentially stochastic and can be modeled as a continuous-time random walk. This model corresponds here to a Gaussian diffusion process. The average speed of the interface and the corresponding diffusion coefficient are determined as functions of the Reynolds number Re, as well as the threshold value above which turbulence contaminates the whole domain. For the lowest values of Re, the stochastic dynamics competes with another deterministic regime of growth of the localized perturbations. The latter is interpreted as a depinning process from the homoclinic snaking region of the system. PMID- 22304199 TI - Segregation by membrane rigidity in flowing binary suspensions of elastic capsules. AB - Spatial segregation in the wall normal direction is investigated in suspensions containing a binary mixture of neo-Hookean capsules subjected to pressure driven flow in a planar slit. The two components of the binary mixture have unequal membrane rigidities. The problem is studied numerically using an accelerated implementation of the boundary integral method. The effect of a variety of parameters was investigated, including the capillary number, rigidity ratio between the two species, volume fraction, confinement ratio, and number fraction of the more floppy particle Xf in the mixture. It was observed that in suspensions of pure species, the mean wall normal positions of the stiff and the floppy particles are comparable. In mixtures, however, the stiff particles were found to be increasingly displaced toward the walls with increasing Xf, while the floppy particles were found to increasingly accumulate near the centerline with decreasing Xf. This segregation behavior was universally observed independent of the parameters. The origin of this segregation is traced to the effect of the number fraction Xf on the localization of the stiff and the floppy particles in the near wall region--the probability of escape of a stiff particle from the near wall region to the interior is greatly reduced with increasing Xf, while the exact opposite trend is observed for a floppy particle with decreasing Xf. Simple model studies on heterogeneous pair collisions involving a stiff and a floppy particle mechanistically explain the contrasting effect of Xf on the near wall localization of the two species. The key observation in these studies is that the stiff particle experiences much larger cross-stream displacement in heterogeneous collisions than the floppy particle. A unified mechanism incorporating the wall induced migration of deformable particles away from the wall and the particle fluxes associated with heterogeneous and homogeneous pair collisions is presented. PMID- 22304200 TI - Phoresis in fluids. AB - This paper presents a unified theory of phoretic phenomena in single-component fluids. Simple formulas are given for the phoretic velocities of small inert force-free non-Brownian particles migrating through otherwise quiescent single component gases and liquids and animated by a gradient in the fluid's temperature (thermophoresis), pressure (barophoresis), density (pycnophoresis), or any combination thereof. The ansatz builds upon a recent paper [Phys. Rev. E 84, 046309 (2011)] concerned with slip of the fluid's mass velocity at solid surfaces -that is, with phenomena arising from violations of the classical no-slip fluid mechanical boundary condition. Experimental and other data are cited in support of the phoretic model developed herein. PMID- 22304201 TI - Axial dipolar dynamo action in the Taylor-Green vortex. AB - We present a numerical study of the magnetic field generated by the Taylor-Green vortex. We show that periodic boundary conditions can be used to mimic realistic boundary conditions by prescribing the symmetries of the velocity and magnetic fields. This gives insight into some problems of central interest for dynamos: the possible effect of velocity fluctuations on the dynamo threshold, and the role of boundary conditions on the threshold and on the geometry of the magnetic field generated by dynamo action. In particular, we show that an axial dipolar dynamo similar to the one observed in a recent experiment can be obtained with an appropriate choice of the symmetries of the magnetic field. The nonlinear saturation is studied and a simple model explaining the magnetic Prandtl number dependence of the super- and subcritical nature of the dynamo transition is given. PMID- 22304202 TI - Low-frequency wave modulations in an electronegative dusty plasma in the presence of charge variations. AB - The effects of dust charge variations on low-frequency wave modulations in an electronegative dusty plasma are investigated. The dynamics of the modulated wave is governed by a nonlinear Schrodinger equation with a dissipative term. The dissipation arises due to the nonsteady (nonadiabatic) dust charge variations. Theoretical and numerical investigations predict the formation of dissipative bright (envelope) and dark solitons. The nonsteady charge-variation-induced dissipation reduces the modulational instability growth rate and introduces a characteristic time scale to observe bright solitons. Results are discussed in the context of electronegative dusty plasma experiments. PMID- 22304203 TI - Dust-acoustic rogue waves in a nonextensive plasma. AB - We present an investigation for the generation of a dust-acoustic rogue wave in a dusty plasma composed of negatively charged dust grains, as well as nonextensive electrons and ions. For this purpose, the reductive perturbation technique is used to obtain a nonlinear Schrodinger equation. The critical wave-number threshold k(c), which indicates where the modulational instability sets in, has been determined precisely for various regimes. Two different behaviors of k(c) against the nonextensive parameter q are found. For small k(c), it is found that increasing q would lead to an increase of k(c) until q approaches a certain value q(c), then further increase of q beyond q(c) decreases the value of k(c). For large k(c), the critical wave-number threshold k(c) is always increasing with q. Within the modulational instability region, a random perturbation of the amplitude grows and thus creates dust-acoustic rogue waves. In order to show that the characteristics of the rogue waves are influenced by the plasma parameters, the relevant numerical analysis of the appropriate nonlinear solution is presented. The nonlinear structure, as reported here, could be useful for controlling and maximizing highly energetic pulses in dusty plasmas. PMID- 22304204 TI - Calculation of electronic transport coefficients of Ag and Au plasma. AB - The thermoelectric transport coefficients of silver and gold plasma have been calculated within the relaxation-time approximation. We considered temperatures of 10-100 kK and densities of rho > T(NL) >> T). We observe that this scale separation is valid in our system. The discrete modes due to the finite size effects are responsible for the disagreement between observations and theory. A crossover from continuous weak turbulence and discrete turbulence is observed when the nonlinear time scale is of the same order of magnitude as the frequency separation of the discrete modes. The Kolmogorov-Zakharov energy cascade is then strongly altered and is frozen before reaching the dissipative regime expected in the theory. PMID- 22304212 TI - Breatherlike electromagnetic wave propagation in an antiferromagnetic medium with Dzyaloshinsky-Moriya interaction. AB - We investigate the nature of propagation of electromagnetic waves (EMWs) in an antiferromagnetic medium with Dzyaloshinsky-Moriya (DM) interaction environment. The interplay of bilinear and DM exchange spin coupling with the magnetic field component of the EMW has been studied by solving Maxwell's equations coupled with a nonlinear spin equation for the magnetization of the medium. We made a nonuniform expansion of the magnetization and magnetic field along the direction of propagation of EMW, in the framework of reductive perturbation method, and the dynamics of the system is found to be governed by a generalized derivative nonlinear Schrodinger (DNLS) equation. We employ the Jacobi-elliptic function method to solve the DNLS equation, and the electromagnetic wave propagation in an antiferromagnetic medium is governed by the breatherlike spatially and temporally coherent localized modes under the influence of DM interaction parameter. PMID- 22304213 TI - Multistable dissipative structures pinned to dual hot spots. AB - We analyze the formation of one-dimensional localized patterns in a nonlinear dissipative medium including a set of two narrow "hot spots" (HSs), which carry the linear gain, local potential, cubic self-interaction, and cubic loss, while the linear loss acts in the host medium. This system can be realized as a spatial domain one in optics and also in Bose-Einstein condensates of quasiparticles in solid-state settings. Recently, exact solutions were found for localized modes pinned to the single HS represented by the delta function. The present paper reports analytical and numerical solutions for coexisting two- and multipeak modes, which may be symmetric or antisymmetric with respect to the underlying HS pair. Stability of the modes is explored through simulations of their perturbed evolution. The sign of the cubic nonlinearity plays a crucial role: in the case of the self-focusing, only the fundamental symmetric and antisymmetric modes, with two local peaks tacked to the HSs, and no additional peaks between them, may be stable. In this case, all the higher-order multipeak modes, being unstable, evolve into the fundamental ones. Stability regions for the fundamental modes are reported. A more interesting situation is found in the case of the self defocusing cubic nonlinearity, with the HS pair giving rise to a multistability, with up to eight coexisting stable multipeak patterns, symmetric and antisymmetric ones. The system without the self-interaction, the nonlinearity being represented only by the local cubic loss, is investigated too. This case is similar to those with the self-focusing or defocusing nonlinearity, if the linear potential of the HS is, respectively, attractive or repulsive. An additional feature of the former setting is the coexistence of the stable fundamental modes with robust breathers. PMID- 22304214 TI - Galilean-invariant algorithm coupling immersed moving boundary conditions and Lees-Edwards boundary conditions. AB - Many investigators have coupled the Lees-Edwards boundary conditions (LEBCs) and suspension methods in the framework of the lattice Boltzmann method to study the pure bulk properties of particle-fluid suspensions. However, these suspension methods are all link-based and are more or less exposed to the disadvantages of violating Galilean invariance. In this paper, we have coupled LEBCs with a node based suspension method, which is demonstrated to be Galilean invariant in benchmark simulations. We use the coupled algorithm to predict the viscosity of a particle-fluid suspension at very low Reynolds number, and the simulation results are in good agreement with the semiempirical Krieger-Dougherty formula. PMID- 22304215 TI - Nonparametric model reconstruction for stochastic differential equations from discretely observed time-series data. AB - A scheme is developed for estimating state-dependent drift and diffusion coefficients in a stochastic differential equation from time-series data. The scheme does not require to specify parametric forms for the drift and diffusion coefficients in advance. In order to perform the nonparametric estimation, a maximum likelihood method is combined with a concept based on a kernel density estimation. In order to deal with discrete observation or sparsity of the time series data, a local linearization method is employed, which enables a fast estimation. PMID- 22304216 TI - Frequency domain description of Kohlrausch response through a pair of Havriliak Negami-type functions: an analysis of functional proximity. AB - An approximation to the Fourier transform (FT) of the Kohlrausch function (stretched exponential) with shape parameter 0 < beta <= 1 is presented by using Havriliak-Negami-like functions. Mathematical expressions to fit their parameters alpha, gamma, and tau, as functions of beta (0 < beta <= 1 and 1 < beta < 2) are given, which allows a quick identification in the frequency domain of the corresponding shape factor beta. Reconstruction via fast Fourier transform of frequency approximants to time domain are shown as good substitutes in short times though biased in long ones (increasing discrepancies as beta -> 1). The method is proposed as a template to commute time and frequency domains when analyzing complex data. Such a strategy facilitates intensive algorithmic search of parameters while adjusting the data of one or several Kohlrausch-Williams Watts relaxations. PMID- 22304217 TI - Particle-tracking simulation of fractional diffusion-reaction processes. AB - Computer simulation of reactive transport in heterogeneous systems remains a challenge due to the multiscale nature of reactive dynamics and the non-Fickian behavior of transport. This study develops a fully Lagrangian approach via particle tracking to describe the reactive transport controlled by the tempered super- or subdiffusion. In the particle-tracking algorithm, the local-scale reaction is affected by the interaction radius between adjacent reactants, whose motion can be simulated by the Langevin equations corresponding to the tempered stable models. Lagrangian simulation results show that the transient superdiffusion enhances the reaction by enhancing the degree of mixing of the reactants. The proposed particle-tracking scheme can also be extended conveniently to multiscale superdiffusion. For the case of transient subdiffusion, the trapping of solutes in the immobile phase can either decrease or accelerate the reaction rate, depending on the initial condition of the reactant particles. Further practical applications show that the new solver efficiently captures bimolecular reactions observed in laboratories. PMID- 22304218 TI - High-order lattice Boltzmann models for gas flow for a wide range of Knudsen numbers. AB - The lattice Boltzmann methods (LBMs) have successfully been applied to microscale flows in the hydrodynamic regime, such as flows of liquids in porous media. However, the LBM in its standard formulation does not produce correct results beyond the hydrodynamic regime, i.e., for slip and transitional ones. Following the work of Shan and He [Phys. Rev. Lett. 80, 65 (1998)], we propose to extend the LBM to these regimes in which nonequilibrium effects are obvious and require us to include a larger number of distribution-function moments. PMID- 22304219 TI - Coevolutionary network approach to cultural dynamics controlled by intolerance. AB - Starting from Axelrod's model of cultural dissemination, we introduce a rewiring probability, enabling agents to cut the links with their unfriendly neighbors if their cultural similarity is below a tolerance parameter. For low values of tolerance, rewiring promotes the convergence to a frozen monocultural state. However, intermediate tolerance values prevent rewiring once the network is fragmented, resulting in a multicultural society even for values of initial cultural diversity in which the original Axelrod model reaches globalization. PMID- 22304220 TI - Two-ball Newton's cradle. AB - Newton's cradle for two balls with Hertzian interactions is considered as a hybrid system, and this makes it possible to derive return maps for the motion between collisions in an exact form despite the fact that the three-halves interaction law cannot be solved in closed form. The return maps depend on a constant whose value can only be determined numerically, but solutions can be written down explicitly in terms of this parameter, and we compare this with the results of simulations. The results are in fact independent of the details of the interaction potential. PMID- 22304221 TI - Quantum turbulent velocity statistics and quasiclassical limit. AB - Two research groups have measured turbulent velocity statistics in superfluid helium using different techniques. The results were in conflict: one experiment revealed Gaussian distributions (as observed in ordinary turbulence), the other experiment determined power laws. To solve the apparent puzzle, we numerically model quantum turbulence as a tangle of vortex filaments, and conclude that there is no contradiction between the two experiments. The transition from Gaussian to power law arises from the different length scales which are probed using the two techniques. We find that the average distance between the quantum vortices marks the separation between quantum and quasiclassical length scales. PMID- 22304222 TI - Comment on "Numerics of the lattice Boltzmann method: effects of collision models on the lattice Boltzmann simulations". AB - Critical comments on the entropic lattice Boltzmann equation (ELBE), by Li-Shi Luo, Wei Liao, Xingwang Chen, Yan Peng, and Wei Zhang in Ref. , are based on simulations, which make use of a model that, despite being referred to as the ELBE by the authors, is in fact equivalent to the standard lattice Bhatnagar Gross-Krook equation for low Mach number simulations. In this Comment, a concise review of the ELBE is provided and illustrated by means of a three-dimensional turbulent flow simulation, which highlights the subgrid features of the ELBE. PMID- 22304223 TI - Household concentrations and exposure of children to particulate matter from biomass fuels in The Gambia. AB - Particulate matter (PM) is an important metric for studying the health effects of household air pollution. There are limited data on PM exposure for children in homes that use biomass fuels, and no previous study has used direct measurement of personal exposure in children younger than 5 years of age. We estimated PM(2.5) exposure for 1266 children in The Gambia by applying the cookhouse PM(2.5)-CO relationship to the child's CO exposure. Using this indirect method, mean PM(2.5) exposure for all subjects was 135 +/- 38 MUg/m(3); 25% of children had exposures of 151 MUg/m(3) or higher. Indirectly estimated exposure was highest among children who lived in homes that used firewood (collected or purchased) as their main fuel (144 MUg/m(3)) compared to those who used charcoal (85 MUg/m(3)). To validate the indirect method, we also directly measured PM(2.5) exposure on 31 children. Mean exposure for this validation data set was 65 +/- 41 MUg/m(3) using actual measurement and 125 +/- 54 MUg/m(3) using the indirect method based on simultaneously-measured CO exposure. The correlation coefficient between direct measurements and indirect estimates was 0.01. Children in The Gambia have relatively high PM(2.5) exposure. There is a need for simple methods that can directly measure PM(2.5) exposure in field studies. PMID- 22304224 TI - Modelling uncertainty estimation for the determination of aflatoxin M(1) in milk by visual and densitometric thin-layer chromatography with immunoaffinity column clean-up. AB - The uncertainty of aflatoxin M(1) concentration in milk, determined by thin-layer chromatography (TLC) with visual and densitometric quantification of the fluorescence intensities of the spots, was estimated using the cause-and-effect approach proposed by ISO GUM (Guide to the expression of uncertainty in measurement) following its main four steps. The sources of uncertainties due to volume measurements, visual and densitometric TLC calibration curve, allowed range for recovery variation and intermediary precision to be taken into account in the uncertainty budget. For volume measurements the sources of uncertainties due to calibration, resolution, laboratory temperature variation and repeatability were considered. For the quantification by visual readings of the intensity of the aflatoxin M(1) in the TLC the uncertainty arising from resolution calibration curves was modelled based on the intervals of concentrations between pairs of the calibration standard solutions. The uncertainty of the densitometric TLC quantification arising from the calibration curve was obtained by weighted least square (WLS) regression. Finally, the repeatability uncertainty of the densitometric peak areas or of the visual readings for the test sample solutions was considered. For the test samples with aflatoxin M(1) concentration between 0.02 and 0.5 ug l(-1), the relative expanded uncertainties, with approximately 95% of coverage probability, obtained for visual TLC readings were between 60% and 130% of the values predicted by the Horwitz model. For the densitometric TLC determination they were about 20% lower. The main sources of uncertainties in both visual and densitometric TLC quantification were the intermediary precision, calibration curve and recovery. The main source of uncertainty in the calibration curve in the visual TLC analysis was due to the resolution of the visual readings, whereas in the densitometric analysis it was due to the peak areas of test sample solutions followed by the intercept and slope uncertainties of the calibration line. PMID- 22304225 TI - AL3810, a multi-tyrosine kinase inhibitor, exhibits potent anti-angiogenic and anti-tumour activity via targeting VEGFR, FGFR and PDGFR. AB - Angiogenesis plays an important role in neoplastic transformation and progression as well as in the metastasis process of most human cancers. Herein, we identified AL3810 as a novel and orally bioavailable small molecular inhibitor with potent inhibitory activity against multiple tyrosine kinases involved in the process of angiogenesis. We found that AL3810 substantially inhibited the autophosphorylation of VEGFR2, PDGFRbeta and FGFR1 in endothelial cells. Moreover, AL3810 exhibited potent anti-angiogenesis activity, manifested by significant inhibition of microvessel outgrowth of rat arterial ring and chickallantochorion membrane (CAM) in ex vivo angiogenesis models. Daily dosing of AL3810 has shown broad-spectrum anti-tumour activity in human kidney, pancreas, liver cancer xenograft models. Importantly, immunohistochemistry results demonstrated that the anti-tumour activity of AL3810 was closely correlated with its anti-angiogenesis activity, as demonstrated by a decreased microvessel area and reduced microvessel numbers in tumour tissues. The overall pharmacological profiles of AL3810 are superior to sorafenib. The clinical trials of AL3810 will soon be launched in China. PMID- 22304226 TI - The asthma ePrompt: a novel electronic solution for chronic disease management. AB - OBJECTIVE: This study tested the ability of an electronic prompt to promote an asthma assessment during primary care visits. METHODS: We performed a prospective study of all eligible adult patients with previously diagnosed asthma in three geographically distinct ambulatory family medicine clinics within a 4-month period. The usual clinic visit process was performed at two geographically distinct control sites (n = 75 and n = 55 patients, respectively). The intervention group site (n = 64) had an electronic flag embedded in the Patient Check-in Locator field which prompted the distribution of a self-administered Asthma Management Questionnaire (AMQ) in the waiting room. The primary outcome measure was a documented asthma severity assessment. RESULTS: The front desk distributed the AMQ successfully in 100% of possible opportunities and the AMQ was completed by 84% of patients. Providers in the intervention group were significantly more likely than providers in the two non-intervention groups to document asthma severity in the medical record during a non-asthma ambulatory clinic visit (63.3% vs. 18.7% vs. 3.6%; p < .001). CONCLUSION: The provision of standardized asthma information triggered by an electronic prompt at the time of check-in effectively initiates an asthma assessment during the primary care visits. PMID- 22304227 TI - Temporal lobe epilepsy with amygdala enlargement: a morphologic and functional study. AB - BACKGROUND AND PURPOSE: Temporal lobe epilepsy (TLE) with nontumoral amygdala enlargement (AE) has been reported to be a possible subtype of TLE without hippocampal sclerosis (HS). The purpose of this study was to clarify morphologic and functional characteristics of TLE with AE (TLE + AE). METHODS: We evaluated gray matter volume and cerebral glucose hypometabolism using magnetic resonance imaging (MRI) voxel-based morphometry (VBM) and voxel-based statistical analysis of [(18) F]-fluorodeoxyglucose positron emission tomography (FDG-PET) images in 9 patients with TLE + AE as compared with controls. For VBM analysis, we recruited 30 age- and sex-matched healthy volunteers as controls. For the comparison of FDG PET analysis, 9 patients with definite mesial TLE with HS (MTLE + HS), and 16 age and sex-matched healthy controls were recruited. RESULTS: In patients with TLE + AE, a significant increase in gray matter volume was found only in the affected amygdala, and no significant decrease in gray matter volume was detected. In addition, significant glucose hypometabolism was observed in the affected amygdala, whereas significant glucose hypometabolism in the hippocampus, a prominent feature of definite MTLE+HS, was not observed. CONCLUSIONS: TLE + AE is different from MTLE + HS from morphologic and functional points of view, and the enlarged amygdala per se is potentially an epileptic focus in patients with partial epilepsy. PMID- 22304229 TI - Selective separation of patchouli alcohol from the essential oil of Cablin potchouli by inclusion crystalline method. AB - In this article, we have focused on the application of non-traditional separation approach, the host-guest inclusion method, into the separation of the active component patchouli alcohol from the essential oil of Cablin potchouli Herb. The host molecule 1,1,6,6-tetraphenylhexa-2,4-diyne-1,6-diol (A) was used to selectively recognise the guest molecule patchouli alcohol (B) in the essential oil of Pogostemon cablin (Blanco) Benth through two strong hydrogen bonding. The inclusion compound was structurally determined by the single crystal X-ray diffraction. The separation effect was examined by gas chromatography for the whole essential oil and the inclusion compound, showing that the inclusion crystalline method is simple, rapid and effective for the separation of patchouli alcohol from the essential oil of C. potchouli Herb. PMID- 22304230 TI - The factor structure of the Revised Illness Perception Questionnaire (IPQ-R) in end-stage renal disease patients. AB - The purpose of this study was to examine the factor structure of the Revised Illness Perceptions Questionnaire (IPQ-R) in a sample of 374 end-stage renal disease (ESRD) patients. A confirmatory factor analysis of the IPQ-R, including the illness identity subscale, demonstrated adequate model fit for the factor structure as originally defined by (Moss-Morris, R., Weinman, J., Petrie, K. J., Horne, R., Cameron, L. D., & Buick, D. (2002). The revised Illness Perception Questionnaire (IPQ-R). Psychology & Health, 17 (1), 1-16.) Modifying the a-priori IPQ-R factor structure by removing two items with low factor loadings and specifying a path between personal control and item 23 had marginally better fit. A separate exploratory factor analysis of the causal items indicated three factors relating to Biological, Psychological and Behavioural causes. These findings provide evidence towards the validity and reliability of the IPQ-R as a suitable measure of illness perceptions in the context of ESRD. PMID- 22304231 TI - The ambivalent academic. PMID- 22304233 TI - Jumbled data cases provide context for teaching quality and safety principles to new accelerated BSN students. PMID- 22304234 TI - Reaction pathway and free energy profiles for butyrylcholinesterase-catalyzed hydrolysis of acetylthiocholine. AB - The catalytic mechanism for butyrylcholineserase (BChE)-catalyzed hydrolysis of acetylthiocholine (ATCh) has been studied by performing pseudobond first principles quantum mechanical/molecular mechanical-free energy (QM/MM-FE) calculations on both acylation and deacylation of BChE. Additional quantum mechanical (QM) calculations have been carried out, along with the QM/MM-FE calculations, to understand the known substrate activation effect on the enzymatic hydrolysis of ATCh. It has been shown that the acylation of BChE with ATCh consists of two reaction steps including the nucleophilic attack on the carbonyl carbon of ATCh and the dissociation of thiocholine ester. The deacylation stage includes nucleophilic attack of a water molecule on the carboxyl carbon of substrate and dissociation between the carboxyl carbon of substrate and hydroxyl oxygen of Ser198 side chain. QM/MM-FE calculation results reveal that the acylation of BChE is rate-determining. It has also been demonstrated that an additional substrate molecule binding to the peripheral anionic site (PAS) of BChE is responsible for the substrate activation effect. In the presence of this additional substrate molecule at PAS, the calculated free energy barrier for the acylation stage (rate-determining step) is decreased by ~1.7 kcal/mol. All of our computational predictions are consistent with available experimental kinetic data. The overall free energy barriers calculated for BChE catalyzed hydrolysis of ATCh at regular hydrolysis phase and substrate activation phase are ~13.6 and ~11.9 kcal/mol, respectively, which are in reasonable agreement with the corresponding experimentally derived activation free energies of 14.0 kcal/mol (for regular hydrolysis phase) and 13.5 kcal/mol (for substrate activation phase). PMID- 22304235 TI - Visuospatial processing in schizophrenia: does it share common mechanisms with pseudoneglect? AB - Schizophrenia patients demonstrate behavioural and cerebral lateralised anomalies, prompting some authors to suggest they exhibit a mild form of right unilateral neglect. To better describe and understand lateralised visuospatial anomalies in schizophrenia, three experiments were run using tasks often utilised to study visuospatial processing in healthy individuals and in neglect patients: the Behavioural Inattention Test (BIT), the manual line bisection task with and without a local cueing paradigm, the landmark task (or line bisection judgement), and the number bisection task. Although the schizophrenia patients did not exhibit the full-blown neglect syndrome, they did demonstrate marked spatial biases that differentiated them from controls on all but two tasks. More specifically, schizophrenia patients showed neither a simple perceptual deficit nor an asymmetry, but demonstrated (1) lateralised anomalies on a simple manual line bisection task; (2) unilateral attentional deficits for line bisection within a local cueing paradigm; and (3) a lateralised deficit in the visuospatial representations of numbers. Altogether, these results suggest a right hemineglect like deficit in schizophrenia in attentional, representational, and motor intentional processes. Yet it does not appear to be as strong a phenomenon. Indeed, it could be considered as an accentuation of the normal asymmetry in visuospatial processing. PMID- 22304236 TI - Antitumor agents. 289. Design, synthesis, and anti-breast cancer activity in vivo of 4-amino-2H-benzo[h]chromen-2-one and 4-amino-7,8,9,10-tetrahydro-2H benzo[h]chromen-2-one analogues with improved water solubility. AB - Previously, we reported that 4-amino-2H-benzo[h]chromen-2-one (ABO) and 4-amino 7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one (ATBO) analogues, which were developed from the lead natural product neo-tanshinlactone, are potent cytotoxic agents. In order to improve on their water solubility, the diamino analogues and related salts were designed. All synthesized compounds were assayed for cytotoxicity, and selected compounds were evaluated for in vivo anti-mammary epithelial proliferation activity in wild-type mice and mice predisposed for mammary tumors due to Brca1/p53 mutations. The new derivatives 10, 16 (ABO), 22, and 27 (ATBO) were the most active analogues, with IC(50) values of 0.038-0.085 MUM in the cytotoxicity assay. Analogue 10 showed around 50-fold improved water solubility compared with the prior lead ABO compound 4-[(4'-methoxyphenyl)amino] 2H-benzo[h]chromen-2-one (3). Compounds 3, 4, 10, and 22 significantly reduced overall numbers of mammary cells, as indicated by the reduction of mammary gland branching in mutant mice. A one-week treatment with 10 resulted in 80% reduction in BrdU-positive cells in the cancer prone mammary gland. These four compounds had differential effects on cellular proliferation and apoptosis in wild-type mouse and a mouse model of human breast cancers. Compound 10 merits further development as a promising anticancer clinical trial candidate. PMID- 22304237 TI - Thymic stromal lymphopoietin: an immune cytokine gene associated with the metabolic syndrome and blood pressure in severe obesity. AB - A previous expression profiling of VAT (visceral adipose tissue) revealed that the TSLP (thymic stromal lymphopoietin) gene was less expressed in severely obese men with (n=7) compared with without (n=7) the MetS (metabolic syndrome). We hypothesized that TSLP SNPs (single nucleotide polymorphisms) are associated with TSLP gene expression in VAT and with MetS phenotypes. Following validation of lower TSLP expression (P=0.003) in VAT of severely obese men and women with (n=70) compared with without (n=60) the MetS, a detailed genetic investigation was performed at the TSLP locus by sequencing its promoter, exons and intron-exon splicing boundaries using DNA of 25 severely obese subjects. Five tagging SNPs were genotyped in the 130 subjects from the expression analysis to test whether these SNPs contributed to TSLP expression variability (ANOVAs) and then genotyped in two independent samples of severely obese men (total, n=389) and women (total, n=894). In a sex-stratified multistage experimental design, ANOVAs were performed to test whether tagging SNPs were associated with MetS components treated as continuous variables. We observed that the non-coding SNP rs2289277 was associated with TSLP mRNA abundance (P=0.04), as well as with SBP [systolic BP (blood pressure)] (P=0.004) and DBP (diastolic BP) (P=0.0003) in men when adjusting for age, waist circumference, smoking and medication treating hypertension. These novel observations suggest that TSLP expression in VAT may partly explain the inter-individual variability for metabolic impairments in the presence of obesity and that specific SNPs (rs2289277 and/or correlating SNPs) may influence TSLP gene expression as well as BP in obese men. PMID- 22304239 TI - p-n Heterojunction on ordered ZnO nanowires/polyaniline microrods double array. AB - Recently, there has been growing interest in the design of novel nano- and/or microscaled heterojunctions consisting of two distinctive ordered semiconductor arrays for highly efficient p-n diodes used in optical, optielectronic, and microelectronic devices. Here, we report the attainment of an ordered double array comprising of p-type polyaniline microrods and n-type ZnO nanowires by a controlled electrochemical deposition method. Extensive chemical and physical characterizations have been performed on the fabricated p-n heterojunction. The double-array p-n heterojunction exhibits good rectifying characteristics, the rectification ratio of which exhibits a minimum at an illumination density of 93 mW cm(-2), making it suitable for high-sensitivity photodetectors. This research is expected to open up a new avenue for the development of highly efficient and sensitive p-n heterojunction diodes and possibly serve as the building blocks for future nanoelectronics. PMID- 22304240 TI - O(2)-evolving chlorite dismutase as a tool for studying O(2)-utilizing enzymes. AB - The direct interrogation of fleeting intermediates by rapid-mixing kinetic methods has significantly advanced our understanding of enzymes that utilize dioxygen. The gas's modest aqueous solubility (<2 mM at 1 atm) presents a technical challenge to this approach, because it limits the rate of formation and extent of accumulation of intermediates. This challenge can be overcome by use of the heme enzyme chlorite dismutase (Cld) for the rapid, in situ generation of O(2) at concentrations far exceeding 2 mM. This method was used to define the O(2) concentration dependence of the reaction of the class Ic ribonucleotide reductase (RNR) from Chlamydia trachomatis, in which the enzyme's Mn(IV)/Fe(III) cofactor forms from a Mn(II)/Fe(II) complex and O(2) via a Mn(IV)/Fe(IV) intermediate, at effective O(2) concentrations as high as ~10 mM. With a more soluble receptor, myoglobin, an O(2) adduct accumulated to a concentration of >6 mM in <15 ms. Finally, the C-H-bond-cleaving Fe(IV)-oxo complex, J, in taurine:alpha-ketoglutarate dioxygenase and superoxo-Fe(2)(III/III) complex, G, in myo-inositol oxygenase, and the tyrosyl-radical-generating Fe(2)(III/IV) intermediate, X, in Escherichia coli RNR, were all accumulated to yields more than twice those previously attained. This means of in situ O(2) evolution permits a >5 mM "pulse" of O(2) to be generated in <1 ms at the easily accessible Cld concentration of 50 MUM. It should therefore significantly extend the range of kinetic and spectroscopic experiments that can routinely be undertaken in the study of these enzymes and could also facilitate resolution of mechanistic pathways in cases of either sluggish or thermodynamically unfavorable O(2) addition steps. PMID- 22304241 TI - On-column labeling of gram-positive bacteria with a boronic acid functionalized squarylium cyanine dye for analysis by polymer-enhanced capillary transient isotachophoresis. AB - A new asymmetric, squarylium cyanine dye functionalized by boronic acid ("SQ-BA") was designed and synthesized for on-capillary labeling of gram-positive bacteria to provide for high sensitivity detection by way of a modified form of capillary electrophoresis with laser induced fluorescence detection (CE-LIF). The CE-based separation employed a polymer-enhanced buffer with capillary transient isotachophoresis in a new hybrid method dubbed "PectI." It was found that the addition of various monosaccharides to SQ-BA in a batch aqueous solution greatly enhanced the emission of the boronic acid functionalized dye by a factor of up to 18.3 at a long wavelength (lambda(ex) = 630 nm, lambda(em) = 660 nm) with a high affinity constant (K = ~10(2.80) M(-1)) superior to other sugar probes. Semiempirical quantum mechanics calculations suggest that the mechanism for this high enhancement may involve the dissociation of initially nonemissive dye associates (stabilized by an intramolecular hydrogen bond) upon complex formation with sugars. The fluorescence emission of SQ-BA was also significantly enhanced in the presence of a gram-positive bacterial spore, Bacillus globigii (Bg), which serves as a simulant of B. anthracis (or anthrax) and which possesses a peptidoglycan (sugar)-rich spore coat to provide ample sites for interaction with the dye. Several peaks were observed for a pure Bg sample even with polyethyleneoxide (PEO) present in the CE separation buffer, despite the polymer's previously demonstrated ability to focus microoorganisms to a single peak during migration. Likewise, several peaks were observed for a Bg sample when capillary transient isotachophoresis (ctITP) alone was employed. However, the new combination of these techniques as "PectI" dramatically and reproducibly focused the bacteria to a single peak with no staining procedure. Using PectI, the trace detection of Bg spores (corresponding to approximately three cells per injection) along with separation efficiency enough to separate Bg from another gram-positive bacteria, Saccharomyces cerevisiae (resolution, R(s) = 6.09, and apparent plate number, N = 2.7-3.3 * 10(5)), were successfully achieved. PMID- 22304242 TI - Effects of dietary protein levels on digestibility of nutrients and growth rate in young female mink (Mustela vison). AB - This study investigated digestibilities of nutrients and feed efficiency in female mink at the different dietary protein levels during the mink growth period. Effects of dietary protein on growth performance of minks were also measured. Sixty 45-day-old healthy female minks were randomly assigned to 6 treatment groups with 10 animals in each group. Animals were fed diets varying in protein levels: 28% (Group I), 30% (Group II), 32% (Group III), 34% (Group IV), 36% (Group V) and 38% (Group VI), respectively. The digestibilities of key nutrients were determined on Day 14 after initiating the experiment and the last 3 days. From the beginning of the study, body weight and feed intake were weighed and recorded every other week in order to calculate the average daily bodyweight gain and the feed efficiency. The trial had demonstrated that nitrogen intake was greatly significantly different, which was affected by dietary protein levels (p < 0.001). Growth performance of minks was impaired when dietary protein level was at 28%. When dietary protein level was at 34%, minks had the best daily gains, feed efficiency, and digestibilities of some key nutrients. PMID- 22304243 TI - Effect of microencapsulation of Lactobacillus salivarus 29 into alginate/chitosan/alginate microcapsules on viability and cytokine induction. AB - Harsh gastric condition causes low bioavailability of probiotics when supplied orally. Polymeric encapsulation has successfully protected bacteria from harsh gastric condition and ultimately increased persistency and multiplication at the targeted region. In this study, we encapsulated LS29 into ACA microcapsules and characterized them. The survivability and release of LS29 from LS29-loaded ACA microcapsules in SGF and SIF were studied. Encapsulation efficiency of LS29 in ACA microcapsules was 99.9%. Approximately 70% of bacteria survived at pH 2 by 120 min after encapsulation. Although not much difference of the survivability of LS29 encapsulated into ACA and FDACA was observed, freeze-drying improved the controlled-release of LS29 in SIF and also showed better storage survivability at 4 degrees C for 8 weeks. Furthermore, investigation of in vitro production of cytokines in RAW264.7 showed high level of induction of TNF-alpha and IL-10. These in vitro results support that the LS29 might have a balanced immunomodulatory effect. PMID- 22304244 TI - Differential response of radish plants to supplemental ultraviolet-B radiation under varying NPK levels: chlorophyll fluorescence, gas exchange and antioxidants. AB - Current and projected increases in ultraviolet-B (UV-B; 280-315 nm) radiation may alter crop growth and yield by modifying the physiological and biochemical functions. This study was conducted to assess the possibility of alleviating the negative effects of supplemental UV-B (sUV-B; 7.2 kJ m-2 day-1; 280-315 nm) on radish (Raphanus sativus var Pusa Himani) by modifying soil nitrogen (N), phosphorus (P) and potassium (K) levels. The N, P and K treatments were recommended dose of N, P and K, 1.5 times recommended dose of N, P and K, 1.5 times recommended dose of N and 1.5 times recommended dose of K. Plants showed variations in their response to UV-B radiation under varying soil NPK levels. The minimum damaging effects of sUV-B on photosynthesis rate and stomatal conductance coupled with minimum reduction in chlorophyll content were recorded for plants grown at recommended dose of NPK. Flavonoids increased under sUV-B except in plants grown at 1.5 times recommended dose of N. Lipid peroxidation (LPO) also increased in response to sUV-B at all NPK levels with maximum at 1.5 times recommended dose of K and minimum at recommended dose of NPK. This study revealed that sUV-B radiation negatively affected the radish plants by reducing the photosynthetic efficiency and increasing LPO. The plants grown at 1.5 times recommended dose of NPK/N/K could not enhance antioxidative potential to the extent as recorded at recommended dose of NPK and hence showed more sensitivity to sUV-B. PMID- 22304245 TI - Variable and complex food web structures revealed by exploring missing trophic links between birds and biofilm. AB - Food webs are comprised of a network of trophic interactions and are essential to elucidating ecosystem processes and functions. However, the presence of unknown, but critical networks hampers understanding of complex and dynamic food webs in nature. Here, we empirically demonstrate a missing link, both critical and variable, by revealing that direct predator-prey relationships between shorebirds and biofilm are widespread and mediated by multiple ecological and evolutionary determinants. Food source mixing models and energy budget estimates indicate that the strength of the missing linkage is dependent on predator traits (body mass and foraging action rate) and the environment that determines food density. Morphological analyses, showing that smaller bodied species possess more developed feeding apparatus to consume biofilm, suggest that the linkage is also phylogenetically dependent and affords a compelling re-interpretation of niche differentiation. We contend that exploring missing links is a necessity for revealing true network structure and dynamics. PMID- 22304246 TI - Optical control of Feshbach resonances in Fermi gases using molecular dark states. AB - We propose a general method for optical control of magnetic Feshbach resonances in ultracold atomic gases with more than one molecular state in an energetically closed channel. Using two optical frequencies to couple two states in the closed channel, inelastic loss arising from spontaneous emission is greatly suppressed by destructive quantum interference at the two-photon resonance, i.e., dark-state formation, while the scattering length is widely tunable by varying the frequencies and/or intensities of the optical fields. This technique is of particular interest for a two-component atomic Fermi gas, which is stable near a Feshbach resonance. PMID- 22304247 TI - Spin-orbit coupled weakly interacting Bose-Einstein condensates in harmonic traps. AB - We investigate theoretically the phase diagram of a spin-orbit coupled Bose gas in two-dimensional harmonic traps. We show that at strong spin-orbit coupling the single-particle spectrum decomposes into different manifolds separated by homega{?}, where omega{?} is the trapping frequency. For a weakly interacting gas, quantum states with Skyrmion lattice patterns emerge spontaneously and preserve either parity symmetry or combined parity-time-reversal symmetry. These phases can be readily observed in a spin-orbit coupled gas of ^{87}Rb atoms in a highly oblate trap. PMID- 22304248 TI - Ramsey numbers and adiabatic quantum computing. AB - The graph-theoretic Ramsey numbers are notoriously difficult to calculate. In fact, for the two-color Ramsey numbers R(m,n) with m, n>=3, only nine are currently known. We present a quantum algorithm for the computation of the Ramsey numbers R(m,n). We show how the computation of R(m,n) can be mapped to a combinatorial optimization problem whose solution can be found using adiabatic quantum evolution. We numerically simulate this adiabatic quantum algorithm and show that it correctly determines the Ramsey numbers R(3,3) and R(2,s) for 5<=s<=7. We then discuss the algorithm's experimental implementation, and close by showing that Ramsey number computation belongs to the quantum complexity class quantum Merlin Arthur. PMID- 22304249 TI - Two-particle bosonic-fermionic quantum walk via integrated photonics. AB - Quantum walk represents one of the most promising resources for the simulation of physical quantum systems, and has also emerged as an alternative to the standard circuit model for quantum computing. Here we investigate how the particle statistics, either bosonic or fermionic, influences a two-particle discrete quantum walk. Such an experiment has been realized by exploiting polarization entanglement to simulate the bunching-antibunching feature of noninteracting bosons and fermions. To this scope a novel three-dimensional geometry for the waveguide circuit is introduced, which allows accurate polarization independent behavior, maintaining remarkable control on both phase and balancement. PMID- 22304250 TI - Measuring neutron-star properties via gravitational waves from neutron-star mergers. AB - We demonstrate by a large set of merger simulations for symmetric binary neutron stars (NSs) that there is a tight correlation between the frequency peak of the postmerger gravitational-wave (GW) emission and the physical properties of the nuclear equation of state (EoS), e.g., expressed by the radius of the maximum mass Tolman-Oppenheimer-Volkhoff configuration. Therefore, a single measurement of the peak frequency of the postmerger GW signal will constrain the NS EoS significantly. For optimistic merger-rate estimates a corresponding detection with Advanced LIGO is expected to happen within an operation time of roughly a year. PMID- 22304251 TI - Resonant shattering of neutron star crusts. AB - The resonant excitation of neutron star (NS) modes by tides is investigated as a source of short gamma-ray burst (SGRB) precursors. We find that the driving of a crust-core interface mode can lead to shattering of the NS crust, liberating ~10{46}-10{47} erg of energy seconds before the merger of a NS-NS or NS-black hole binary. Such properties are consistent with Swift/BAT detections of SGRB precursors, and we use the timing of the observed precursors to place weak constraints on the crust equation of state. We describe how a larger sample of precursor detections could be used alongside coincident gravitational wave detections of the inspiral by Advanced LIGO class detectors to probe the NS structure. These two types of observations nicely complement one another, since the former constrains the equation of state and structure near the crust-core boundary, while the latter is more sensitive to the core equation of state. PMID- 22304253 TI - Regenerating a symmetry in asymmetric dark matter. AB - Asymmetric dark matter theories generically allow for mass terms that lead to particle-antiparticle mixing. Over the age of the Universe, dark matter can thus oscillate from a purely asymmetric configuration into a symmetric mix of particles and antiparticles, allowing for pair-annihilation processes. Additionally, requiring efficient depletion of the primordial thermal (symmetric) component generically entails large annihilation rates. We show that unless some symmetry completely forbids dark matter particle-antiparticle mixing, asymmetric dark matter is effectively ruled out for a large range of masses, for almost any oscillation time scale shorter than the age of the Universe. PMID- 22304254 TI - Expanding (3+1)-dimensional universe from a lorentzian matrix model for superstring theory in (9+1) dimensions. AB - We reconsider the matrix model formulation of type IIB superstring theory in (9+1)-dimensional space-time. Unlike the previous works in which the Wick rotation was used to make the model well defined, we regularize the Lorentzian model by introducing infrared cutoffs in both the spatial and temporal directions. Monte Carlo studies reveal that the two cutoffs can be removed in the large-N limit and that the theory thus obtained has no parameters other than one scale parameter. Moreover, we find that three out of nine spatial directions start to expand at some "critical time," after which the space has SO(3) symmetry instead of SO(9). PMID- 22304252 TI - Measurement of separate cosmic-ray electron and positron spectra with the fermi large area telescope. AB - We measured separate cosmic-ray electron and positron spectra with the Fermi Large Area Telescope. Because the instrument does not have an onboard magnet, we distinguish the two species by exploiting Earth's shadow, which is offset in opposite directions for opposite charges due to Earth's magnetic field. We estimate and subtract the cosmic-ray proton background using two different methods that produce consistent results. We report the electron-only spectrum, the positron-only spectrum, and the positron fraction between 20 and 200 GeV. We confirm that the fraction rises with energy in the 20-100 GeV range. The three new spectral points between 100 and 200 GeV are consistent with a fraction that is continuing to rise with energy. PMID- 22304256 TI - Resummation for W and Z production at large p{T}. AB - Soft-collinear effective theory is used to perform threshold resummation for W and Z production at large transverse momentum to next-to-next-to-leading logarithmic accuracy including matching to next-to-leading fixed-order results. The results agree very well with data from the Tevatron, and predictions are made for the high-p{T} spectra at the LHC. While the higher-log terms are of moderate size, their inclusion leads to a substantial reduction of the perturbative uncertainty. With these improvements, the parton distribution function uncertainties now dominate the error on the predicted cross section. PMID- 22304257 TI - Self-consistent Green's function calculation of the nucleon mean free path. AB - The extension of Green's functions techniques to the complex energy plane provides access to fully dressed quasiparticle properties from a microscopic perspective. Using self-consistent ladder self-energies, we find both spectra and lifetimes of such quasiparticles in nuclear matter. With a consistent choice of the group velocity, the nucleon mean-free path can be computed. Our results indicate that, for energies above 50 MeV at densities close to saturation, a nucleon has a mean-free path of 4 to 5 fm. PMID- 22304258 TI - Probing electronic coherence in a gas of dipole-dipole coupled Rydberg atoms. AB - We demonstrate a novel time-domain method to probe electronic coherence in ensembles of cold Rydberg atoms coupled via nearly resonant dipole-dipole interactions. Short laser pulses create coherent superpositions of few-electron eigenstates which evolve under the influence of pulsed electric fields. The pulses steer the dynamics, enhancing the probability for finding atoms in np, rather than initially excited ns states. The enhancement reflects the underlying electronic coherence which persists for >10 MUs, 2 orders of magnitude longer than previously measured dephasing times in the same system. Simulations suggest that atom motion is responsible for the eventual decoherence. PMID- 22304259 TI - Interaction enhanced imaging of individual Rydberg atoms in dense gases. AB - We propose a new all-optical method to image individual Rydberg atoms embedded within dense gases of ground state atoms. The scheme exploits interaction-induced shifts on highly polarizable excited states of probe atoms, which can be spatially resolved via an electromagnetically induced transparency resonance. Using a realistic model, we show that it is possible to image individual Rydberg atoms with enhanced sensitivity and high resolution despite photon-shot noise and atomic density fluctuations. This new imaging scheme could be extended to other impurities such as ions, and is ideally suited to equilibrium and dynamical studies of complex many-body phenomena involving strongly interacting particles. As an example we study blockade effects and correlations in the distribution of Rydberg atoms optically excited from a dense gas. PMID- 22304260 TI - Optical Thomas-Reiche-Kuhn sum rules. AB - The Thomas-Reiche-Kuhn sum rule is a fundamental consequence of the position momentum commutation relation for an atomic electron and it provides an important constraint on the transition matrix elements for an atom. Analogously, the commutation relations for the electromagnetic field operators in a magnetodielectric medium constrain the properties of the dispersion relations for the medium through four sum rules for the allowed phase and group velocities for polaritons propagating through the medium. These rules apply to all bulk media including the metamaterials designed to provide negative refractive indices. An immediate consequence of this is that it is not possible to construct a medium in which all the polariton modes for a given wavelength lie in the negative-index region. PMID- 22304261 TI - Experiments on elastic cloaking in thin plates. AB - Following a theoretical proposal [M. Farhat et al., Phys. Rev. Lett. 103, 024301 (2009)], we design, fabricate, and characterize a cloaking structure for elastic waves in 1 mm thin structured polymer plates. The cloak consists of 20 concentric rings of 16 different metamaterials, each being a tailored composite of polyvinyl chloride and polydimethylsiloxane. By using stroboscopic imaging with a camera from the direction normal to the plate, we record movies of the elastic waves for monochromatic plane-wave excitation. We observe good cloaking behavior for carrier frequencies in the range from 200 to 400 Hz (one octave), in good agreement with a complete continuum-mechanics numerical treatment. This system is thus ideally suited for demonstration experiments conveying the ideas of transformation optics. PMID- 22304262 TI - Anomalous exponents at the onset of an instability. AB - Critical exponents are calculated exactly at the onset of an instability, by using asymptotic expansion techniques. When the unstable mode is subject to multiplicative noise whose spectrum at zero frequency vanishes, we show that the critical behavior can be anomalous; i.e., the mode amplitude X scales with departure from onset MU as ?MU(beta) with an exponent beta different from its deterministic value. This behavior is observed in a direct numerical simulation of the dynamo instability, and our results provide a possible explanation for recent experimental observations. PMID- 22304255 TI - Search for a Higgs boson in the diphoton final state in pp collisions at sqrt[s]=1.96 TeV. AB - A search for a narrow Higgs boson resonance in the diphoton mass spectrum is presented based on data corresponding to 7.0 fb{-1} of integrated luminosity from pp collisions at sqrt[s]=1.96 TeV collected by the CDF experiment. No evidence of such a resonance is observed, and upper limits are set on the cross section times branching ratio of the resonant state as a function of Higgs boson mass. The limits are interpreted in the context of the standard model and one fermiophobic benchmark model where the data exclude fermiophobic Higgs bosons with masses below 114 GeV/c{2} at a 95% Bayesian credibility level. PMID- 22304263 TI - Deflection of MeV protons by an unbent half-wavelength silicon crystal. AB - The interaction of a 2 MeV proton beam with an ultrathin unbent Si crystal was studied through simulation and experiment. Crystal thickness along the beam was set at 92 nm, i.e., at half the oscillation wavelength of the protons in the crystal under planar channeling condition. As the nominal beam direction is inclined by less than the critical angle for planar channeling with respect to the crystal planes, under-barrier particles undergo half an oscillation and exit the crystal with the reversal of the transverse momenta; i.e., the protons are "mirrored" by the crystal planes. Over-barrier particles suffer deflection, too, to a direction opposite that of mirroring with a dynamics similar to that of volume reflection in a bent crystal. On the strength of such coherent interactions, charged particle beams can be efficiently steered through an ultrathin unbent crystal by the same physical processes as for thicker bent crystals. PMID- 22304264 TI - Quantum tunneling of a vortex between two pinning potentials. AB - A vortex can tunnel between two pinning potentials in an atomic Bose-Einstein condensate on a time scale of the order of 1s under typical experimental conditions. This makes it possible to detect the tunneling experimentally. We calculate the tunneling rate by phenomenologically treating vortices as charged particles moving in an inhomogeneous magnetic field. The obtained results are in close agreement with numerical simulations based on the stochastic c-field theory. PMID- 22304265 TI - Scaling in the diffusion limited aggregation model. AB - We present a self-consistent picture of diffusion limited aggregation (DLA) growth based on the assumption that the probability density P(r,N) for the next particle to be attached within the distance r to the center of the cluster is expressible in the scale-invariant form P[r/R{dep}(N)]. It follows from this assumption that there is no multiscaling issue in DLA and there is only a single fractal dimension D for all length scales. We check our assumption self consistently by calculating the particle-density distribution with a measured P(r/R{dep}) function on an ensemble with 1000 clusters of 5*10{7} particles each. We also show that a nontrivial multiscaling function D(x) can be obtained only when small clusters (N<10 000) are used to calculate D(x). Hence, multiscaling is a finite-size effect and is not intrinsic to DLA. PMID- 22304266 TI - Analytical results for size-topology correlations in 2D disk and cellular packings. AB - Random tilings or packings in the plane are characterized by a size distribution of individual elements (domains) and by the statistics of neighbor relations between the domains. Most systems occurring in nature or technology have a unimodal distribution of both areas and number of neighbors. Empirically, strong correlations between these distributions have been observed and formulated as universal laws. Using only the local, correlation-free granocentric model approach with no free parameters, we construct accurate analytical descriptions for disk crystallization, size-topology correlations, and Lemaitre's law. PMID- 22304267 TI - Sliding velocity dependence of adhesion in a nanometer-sized contact. AB - The influence of sliding velocity on the adhesion force in a nanometer-sized contact was investigated with a novel atomic force microscope experimental setup that allows measuring adhesion forces while the probe is sliding at continuous and constant velocities. For hydrophobic surfaces, the adhesion forces (mainly van der Waals forces) remain constant, whereas for hydrophilic surfaces, adhesion forces (mainly capillary forces) decrease linearly with a logarithmic increase of the sliding velocity. The experimental data are well explained by a model based on a thermally activated growth process of a capillary meniscus. PMID- 22304268 TI - Tensile plasticity in metallic glasses with pronounced beta relaxations. AB - Metallic glasses are commonly brittle, as they generally fail catastrophically under uniaxial tension. Here we show pronounced macroscopic tensile plasticity achieved in a La-based metallic glass which possesses strong beta relaxations and nanoscale heterogeneous structures. We demonstrate that the beta relaxation is closely correlated with the activation of the structural units of plastic deformations and global plasticity, and the transition from brittle to ductile in tension and the activation of the beta relaxations follow a similar time temperature scaling relationship. The results have implications for understanding the mechanisms of plastic deformation and structural origin of beta relaxations as well as for solving the brittleness in metallic glasses. PMID- 22304269 TI - Oscillatory energy exchange between waves coupled by a dynamic artificial crystal. AB - We describe a general mechanism of controllable energy exchange between waves propagating in a dynamic artificial crystal. We show that if a spatial periodicity is temporarily imposed on the transmission properties of a wave carrying medium while a wave is inside, this wave is coupled to a secondary counterpropagating wave and energy oscillates between the two. The oscillation frequency is determined by the width of the spectral band gap created by the periodicity and the frequency difference between the coupled waves. The effect is demonstrated with spin waves in a dynamic magnonic crystal. PMID- 22304270 TI - Anomalous electrical conductivity behavior at elevated pressure in the protic ionic liquid procainamide hydrochloride. AB - Using broadband dielectric spectroscopy, we investigated the effect of hydrostatic pressure on the conductivity relaxation time tau{sigma} of the supercooled protic ionic liquid, procainamide hydrochloride, a common pharmaceutical. The pressure dependence of tau{sigma} exhibited anomalous behavior in the vicinity of the glass transition T{g}, manifested by abrupt changes in activation volume. This peculiar behavior, paralleling the change in temperature dependence of tau{sigma} near T{g}, is a manifestation of the decoupling between electrical conductivity and structural relaxation. Although the latter effectively ceases in the glassy state, free ions retain their mobility but with a reduced sensitivity to thermodynamic changes. This is the first observation of decoupling of ion migration from structural relaxation in a glassy conductor by isothermal densification. PMID- 22304271 TI - Beyond Millikan: the dynamics of charging events on individual colloidal particles. AB - By measuring the stable charge on oil drops in air, Millikan demonstrated the discrete nature of electric charge. We extend his approach to the charge on solid liquid interfaces, and focus on the dynamics of the discrete fluctuations. Our measurements are accurate and fast enough to observe changes of one elementary charge. Experiments over thousands of seconds yield information about the fast dynamics of electrochemical reactions, relevant for physicochemical and biological systems. As an example, we study (dis)charging processes on colloidal particles in a nonpolar liquid. PMID- 22304272 TI - Growth inside a corner: the limiting interface shape. AB - We investigate the growth of a crystal that is built by depositing cubes inside a corner. The interface of this crystal approaches a deterministic growing limiting shape in the long-time limit. Building on known results for the corresponding two dimensional system and accounting for basic three-dimensional symmetries, we conjecture a governing equation for the evolution of the interface profile. We solve this equation analytically and find excellent agreement with simulations of the growth process. We also present a generalization to arbitrary spatial dimension. PMID- 22304273 TI - Landau quantization and the thickness limit of topological insulator thin films of Sb2Te3. AB - We report the experimental observation of Landau quantization of molecular beam epitaxy grown Sb{2}Te{3} thin films by a low-temperature scanning tunneling microscope. Different from all the reported systems, the Landau quantization in a Sb{2}Te{3} topological insulator is not sensitive to the intrinsic substitutional defects in the films. As a result, a nearly perfect linear energy dispersion of surface states as a 2D massless Dirac fermion system is achieved. We demonstrate that four quintuple layers are the thickness limit for a Sb{2}Te{3} thin film being a 3D topological insulator. The mechanism of the Landau-level broadening is discussed in terms of enhanced quasiparticle lifetime. PMID- 22304274 TI - Temperature-dependent Fermi surface evolution in heavy fermion CeIrIn5. AB - We address theoretically the evolution of the heavy fermion Fermi surface (FS) as a function of temperature (T), using a first principles dynamical mean-field theory approach combined with density functional theory. We focus on the archetypical heavy electrons in CeIrIn{5}. Upon cooling, both the quantum oscillation frequencies and cyclotron masses show logarithmic scaling behavior [~ln(T{0}/T)] with different characteristic temperatures T{0}=130 and 50 K, respectively. The enlargement of the electron FSs at low T is accompanied by topological changes around T=10-50 K. The resistivity coherence peak observed at T?50 K is the result of the competition between the binding of incoherent 4f electrons to the spd conduction electrons at Fermi level (E{F}) and the formation of coherent 4f electrons. PMID- 22304275 TI - Electronic confinement and ordering instabilities in colossal magnetoresistive bilayer manganites. AB - We present angle-resolved photoemission studies of (La{1-z}Pr{z}){2 2x}Sr{1+2x}Mn{2}O{7} with x=0.4 and z=0.1, 0.2, and 0.4 along with density functional theory calculations and x-ray scattering data. Our results show that the bilayer splitting in the ferromagnetic metallic phase of these materials is small, if not completely absent. The charge carriers are therefore confined to a single MnO{2} layer, which in turn results in a strongly nested Fermi surface. In addition to this, the spectral function also displays clear signatures of an electronic ordering instability well below the Fermi level. The increase of the corresponding interaction strength with z and its magnitude of ~400 meV make the coupling to a bare phonon highly unlikely. Instead we conclude that fluctuating order, involving electronic and lattice degrees of freedom, causes the observed renormalization of the spectral features. PMID- 22304276 TI - Spin relaxation near the metal-insulator transition: dominance of the Dresselhaus spin-orbit coupling. AB - We identify the Dresselhaus spin-orbit coupling as the source of the dominant spin-relaxation mechanism in the impurity band of a wide class of n-doped zinc blende semiconductors. The Dresselhaus hopping terms are derived and incorporated into a tight-binding model of impurity sites, and they are shown to unexpectedly dominate the spin relaxation, leading to spin-relaxation times in good agreement with experimental values. This conclusion is drawn from two complementary approaches: an analytical diffusive-evolution calculation and a numerical finite size scaling study of the spin-relaxation time. PMID- 22304277 TI - Long-wavelength local density of states oscillations near graphene step edges. AB - Using scanning tunneling microscopy and spectroscopy, we have studied the local density of states (LDOS) of graphene over step edges in boron nitride. Long wavelength oscillations in the LDOS are observed with maxima parallel to the step edge. Their wavelength and amplitude are controlled by the energy of the quasiparticles allowing a direct probe of the graphene dispersion relation. We also observe a faster decay of the LDOS oscillations away from the step edge than in conventional metals. This is due to the chiral nature of the Dirac fermions in graphene. PMID- 22304278 TI - Surface origin of high conductivities in undoped In2O3 thin films. AB - The microscopic cause of conductivity in transparent conducting oxides like ZnO, In{2}O{3}, and SnO{2} is generally considered to be a point defect mechanism in the bulk, involving intrinsic lattice defects, extrinsic dopants, or unintentional impurities like hydrogen. We confirm here that the defect theory for O-vacancies can quantitatively account for the rather moderate conductivity and off-stoichiometry observed in bulk In{2}O{3} samples under high-temperature equilibrium conditions. However, nominally undoped thin-films of In{2}O{3} can exhibit surprisingly high conductivities exceeding by 4-5 orders of magnitude that of bulk samples under identical conditions (temperature and O{2} partial pressure). Employing surface calculations and thickness-dependent Hall measurements, we demonstrate that surface donors rather than bulk defects dominate the conductivity of In{2}O{3} thin films. PMID- 22304279 TI - Spin fluctuations and the peak-dip-hump feature in the photoemission spectrum of actinides. AB - We present first-principles multiband spin susceptibility calculations within the random-phase approximation for four isostructural superconducting PuCoIn{5}, PuCoGa{5}, PuRhGa{5}, and nonsuperconducting UCoGa{5} actinides. The results show that a strong peak in the spin-fluctuation dressed self-energy is present around 0.5 eV in all materials, which is mostly created by 5f electrons. These fluctuations couple to the single-particle spectrum and give rise to a peak-dip hump feature, characteristic of the coexistence of itinerant and localized electronic states. Results are in quantitative agreement with photoemission spectra. Finally, we show that the studied actinides can be understood within the rigid-band filling approach, in which the spin-fluctuation coupling constant follows the same materials dependence as the superconducting transition temperature T{c}. PMID- 22304280 TI - Enhancement of the critical temperature of superconductors by Anderson localization. AB - The influence of disorder on the temperature of superconducting transition (T{c}) is studied within the sigma-model renormalization-group framework. Electron electron interaction in particle-hole and Cooper channels is taken into account and assumed to be short range. Two-dimensional systems in the weak localization and antilocalization regime, as well as systems near mobility edge are considered. It is shown that in all these regimes Anderson localization leads to strong enhancement of T{c} related to the multifractality of wave functions. Screening of the long-range Coulomb interaction thus opens a promising direction for searching novel materials for high-T{c} superconductivity. PMID- 22304281 TI - Electrical measurement of antiferromagnetic moments in exchange-coupled IrMn/NiFe stacks. AB - We employ antiferromagnetic tunneling anisotropic magnetoresistance to study the behavior of antiferromagnetically ordered moments in IrMn exchange coupled to NiFe. Experiments performed by common laboratory tools for magnetization and electrical transport measurements allow us to directly link the broadening of the NiFe hysteresis loop and its shift (exchange bias) to the rotation and pinning of antiferromagnetic moments in IrMn. At higher temperatures, the broadened loops show zero shift, which correlates with the observation of fully rotating antiferromagnetic moments inside the IrMn film. The onset of exchange bias at lower temperatures is linked to a partial rotation between distinct metastable states and pinning of the IrMn antiferromagnetic moments in these states. The observation complements common pictures of exchange bias and reveals an electrically measurable memory effect in an antiferromagnet. PMID- 22304282 TI - Electrostatic spin crossover in a molecular junction of a single-molecule magnet Fe{2}. AB - Spin crossover by means of an electric bias is investigated by spin-polarized density-functional theory calculations combined with the Keldysh nonequilibrium Green's technique in a molecular junction, where an individual single-molecule magnet Fe{2}(acpybutO)(O{2}CMe)(NCS){2} is sandwiched between two infinite Au(100) nanoelectrodes. Our study demonstrates that the spin crossover, based on the Stark effect, is achieved in this molecular junction under an electric bias but not in the isolated molecule under external electric fields. The main reason is that the polarizability of the molecular junction has an opposite sign to that of the isolated molecule, and thus from the Stark effect the condition for the spin crossover in the molecular junction is contrary to that in the isolated molecule. PMID- 22304283 TI - Time-domain measurement of current-induced spin wave dynamics. AB - The performance of spintronic devices critically depends on three material parameters, namely, the spin polarization in the current (P), the intrinsic Gilbert damping (alpha), and the coefficient of the nonadiabatic spin transfer torque (beta). However, there has been no method to determine these crucial material parameters in a self-contained manner. Here we show that P, alpha, and beta can be simultaneously determined by performing a single series of time domain measurements of current-induced spin wave dynamics in a ferromagnetic film. PMID- 22304284 TI - Empirical magnetic structure solution of frustrated spin systems. AB - Frustrated magnetism plays a central role in the phenomenology of exotic quantum states. However, since the magnetic structures of frustrated systems are often aperiodic, there has been the problem that they cannot be determined by using traditional crystallographic techniques. Here we show that the magnetic component of powder neutron scattering data is actually sufficiently information-rich to drive magnetic structure solution for frustrated systems, including spin ices, spin liquids, and molecular magnets. Our methodology employs ab initio reverse Monte Carlo refinement, making informed use of an additional constraint that minimizes variance in local spin environments. The atomistic spin configurations obtained in this way not only reflect a magnetic structure "solution" but also reproduce the full three-dimensional magnetic scattering pattern. PMID- 22304285 TI - Exact ground states with deconfined gapless excitations for the three-leg spin 1/2 tube. AB - We consider a spin-1/2 tube (a three-leg ladder with periodic boundary conditions) with a Hamiltonian given by two projection operators-one on the triangles and the other on the square plaquettes on the side of the tube-that can be written in terms of Heisenberg and four-spin ring exchange interactions. We identify 3 phases: (i) for strongly antiferromagnetic exchange on the triangles, an exact ground state with a gapped spectrum can be given as an alternation of spin and chirality singlet bonds between nearest triangles; (ii) for ferromagnetic exchange on the triangles, we recover the phase of the spin-3/2 Heisenberg chain; (iii) between these two phases, a gapless incommensurate phase exists. We construct an exact ground state with two deconfined domain walls and a gapless excitation spectrum at the quantum phase transition point between the incommensurate and dimerized phases. PMID- 22304286 TI - Multiple-q states and the Skyrmion lattice of the triangular-lattice Heisenberg antiferromagnet under magnetic fields. AB - Ordering of the frustrated classical Heisenberg model on the triangular lattice with an incommensurate spiral structure is studied under magnetic fields by means of a mean-field analysis and a Monte Carlo simulation. Several types of multiple q states including the Skyrmion-lattice state is observed in addition to the standard single-q state. In contrast to the Dzyaloshinskii-Moriya interaction driven system, the present model allows both Skyrmions and anti-Skyrmions, together with a new thermodynamic phase where Skyrmion and anti-Skyrmion lattices form a domain state. PMID- 22304287 TI - Spin guides and spin splitters: waveguide analogies in one-dimensional spin chains. AB - Here we show a mapping between waveguide theory and spin-chain transport, opening an alternative approach to solid-state quantum information transport. By applying temporally varying control profiles to a spin chain, we design a virtual waveguide or "spin guide" to conduct spin excitations along defined space-time trajectories of the chain. We show that the concepts of confinement, adiabatic bend loss, and beam splitting can be mapped from optical waveguide theory to spin guides, and hence to "spin splitters." Importantly, the spatial scale of applied control pulses is required to be large compared to the interspin spacing, thereby allowing the design of scalable control architectures. PMID- 22304288 TI - Resonance fluorescence from semiconductor quantum dots: beyond the Mollow triplet. AB - We show that the resonance fluorescence spectrum of a quantum dot excited by a strong optical pulse contains multiple peaks beyond those of the Mollow triplet. We show that as the area of the optical pulse is increased, new side peaks split off the central peak and shift in frequency. A simple analytical theory has been derived, which quantitatively accounts for the appearance and position of the peaks. This theory explains the physics responsible for the multiple peaks. By considering the time-dependent spectrum we demonstrate a time ordering of the side peaks, which is further evidence for the suggested physical explanation. PMID- 22304289 TI - Coherent optical control of the spin of a single hole in an InAs/GaAs quantum dot. AB - We demonstrate coherent optical control of a single hole spin confined to an InAs/GaAs quantum dot. A superposition of hole-spin states is created by fast (10 100 ps) dissociation of a spin-polarized electron-hole pair. Full control of the hole spin is achieved by combining coherent rotations about two axes: Larmor precession of the hole spin about an external Voigt geometry magnetic field, and rotation about the optical axis due to the geometric phase shift induced by a picosecond laser pulse resonant with the hole-trion transition. PMID- 22304290 TI - Spin-wave modes and their intense excitation effects in Skyrmion crystals. AB - We theoretically study spin-wave modes and their intense excitations activated by microwave magnetic fields in the Skyrmion-crystal phase of insulating magnets by numerically analyzing a two-dimensional spin model using the Landau-Lifshitz Gilbert equation. Two peaks of spin-wave resonances with frequencies of ~1 GHz are found for in-plane ac magnetic field where distribution of the out-of-plane spin components circulates around each Skyrmion core. Directions of the circulations are opposite between these two modes, and hence the spectra exhibit a salient dependence on the circular polarization of irradiating microwave. A breathing-type mode is also found for an out-of-plane ac magnetic field. By intensively exciting these collective modes, melting of the Skyrmion crystal accompanied by a redshift of the resonant frequency is achieved within nanoseconds. PMID- 22304291 TI - Cyclotron motion in the vicinity of a Lifshitz transition in graphite. AB - Graphite, a model (semi)metal with trigonally warped bands, is investigated with a magnetoabsorption experiment and viewed as an electronic system in the vicinity of the Lifshitz transition. A characteristic pattern of up to 20 cyclotron resonance harmonics has been observed. This large number of resonances, their relative strengths and characteristic shapes trace the universal properties of the electronic states near a separatrix in momentum space. Quantum-mechanical perturbative methods with respect to the trigonal warping term hardly describe the data which are, on the other hand, fairly well reproduced within a quasiclassical approach and conventional band structure model. Trigonal symmetry is preserved in graphite in contrast to a similar system, bilayer graphene. PMID- 22304292 TI - Frustrated order on extrinsic geometries. AB - We study, numerically and theoretically, defects in an anisotropic liquid that couple to the extrinsic geometry of a surface. Though the intrinsic geometry tends to confine topological defects to regions of large Gaussian curvature, extrinsic couplings tend to orient the order along the local direction of maximum or minimum bending. This additional frustration is generically unavoidable, and leads to complex ground-state thermodynamics. Using the catenoid as a prototype, we show, in contradistinction to the well-known effects of intrinsic geometry, that extrinsic curvature expels disclinations from the region of maximum curvature above a critical coupling threshold. On catenoids lacking an "inside outside" symmetry, defects are expelled altogether above a critical neck size. PMID- 22304293 TI - Equipartition of rotational and translational energy in a dense granular gas. AB - Experiments quantifying the rotational and translational motion of particles in a dense, driven, 2D granular gas floating on an air table reveal that kinetic energy is divided equally between the two translational and one rotational degrees of freedom. This equipartition persists when the particle properties, confining pressure, packing density, or spatial ordering are changed. While the translational velocity distributions are the same for both large and small particles, the angular velocity distributions scale with the particle radius. The probability distributions of all particle velocities have approximately exponential tails. Additionally, we find that the system can be described with a granular Boyle's law with a van der Waals-like equation of state. These results demonstrate ways in which conventional statistical mechanics can unexpectedly apply to nonequilibrium systems. PMID- 22304294 TI - Optically trapped gold nanoparticle enables listening at the microscale. AB - We explore a new application of optical tweezers for ultrasensitive detection of sound waves in liquid media. Position tracking of a single gold nanoparticle confined in a three-dimensional optical trap is used to readout acoustic vibrations at a sound power level down to -60 dB, causing a ~90 MUeV increase in kinetic energy of the nanoparticle. The unprecedented sensitivity of such a nanoear is achieved by processing the nanoparticle's motion in the frequency domain. The concept developed here will enable us to access the interior of biological microorganisms and micromechanical machines not accessible by other microscopy types. PMID- 22304295 TI - Competition for catalytic resources alters biological network dynamics. AB - Genetic regulation networks orchestrate many complex cellular behaviors. Dynamic operations that take place within cells are thus dependent on the gene expression machinery, enabled by powerful enzymes such as polymerases, ribosomes, or nucleases. These generalist enzymes typically process many different substrates, potentially leading to competitive situations: by saturating the common enzyme, one substrate may down-regulate its competitors. However, most theoretical or experimental models simply omit these effects, focusing on the pattern of genetic regulatory interactions as the main determinant of network function. We show here that competition effects have important outcomes, which can be spotted within the global dynamics of experimental systems. Further we demonstrate that enzyme saturation creates a layer of cross couplings that may foster, but also hamper, the expected behavior of synthetic biology constructs. PMID- 22304296 TI - Genistein as a potential inducer of the anti-atherogenic enzyme paraoxonase-1: studies in cultured hepatocytes in vitro and in rat liver in vivo. AB - A number of cardioprotective effects, including the reduced oxidation of the low density lipoprotein (LDL) particles, have been attributed to dietary soy isoflavones. Paraoxonase 1 (PON1), an enzyme mainly synthesized in the liver, may exhibit anti-atherogenic activity by protecting LDL from oxidation. Thus, dietary and pharmacological inducers of PON1 may decrease cardiovascular disease risk. Using a luciferase reporter gene assay we screened different flavonoids for their ability to induce PON1 in Huh7 hepatocytes in culture. Genistein was the most potent flavonoid with regard to its PON1-inducing activity, followed by daidzein, luteolin, isorhamnetin and quercetin. Other flavonoids such as naringenin, cyanidin, malvidin and catechin showed only little or no PON1-inducing activity. Genistein-mediated PON1 transactivation was partly inhibited by the oestrogen receptor antagonist fulvestrant as well as by the aryl hydrocarbon receptor antagonist 7-ketocholesterol. In contrast to genistein, the conjugated genistein metabolites genistein-7-glucuronide, genistein-7-sulfate and genistein-7,4' disulfate were only weak inducers of PON1 transactivation. Accordingly, dietary genistein supplementation (2 g/kg diet over three weeks) in growing rats did not increase hepatic PON1 mRNA and protein levels as well as plasma PON1 activity. Thus, genistein may be a PON1 inducer in cultured hepatocytes in vitro, but not in rats in vivo. PMID- 22304297 TI - Effect of Ca2+ and Zn2+ on UO2 dissolution rates. AB - The dissolution of UO(2) in a continuously stirred tank reactor (CSTR) in the presence of Ca(2+) and Zn(2+) was investigated under experimental conditions relevant to contaminated groundwater systems. Complementary experiments were performed to investigate the effect of adsorption and precipitation reactions on UO(2) dissolution. The experiments were performed under anoxic and oxic conditions. Zn(2+) had a much greater inhibitory effect on UO(2) dissolution than did Ca(2+). This inhibition was most substantial under oxic conditions, where the experimental rate of UO(2) dissolution was 7 times lower in the presence of Ca(2+) and 1450 times lower in the presence of Zn(2+) than in water free of divalent cations. EXAFS and solution chemistry analyses of UO(2) solids recovered from a Ca experiment suggest that a Ca-U(VI) phase precipitated. The Zn carbonate hydrozincite [Zn(5)(CO(3))(2)(OH)(6)] or a structurally similar phase precipitated on the UO(2) solids recovered from experiments performed in the presence of Zn. These precipitated Ca and Zn phases can coat the UO(2) surface, inhibiting the oxidative dissolution of UO(2). Interactions with divalent groundwater cations have implications for the longevity of UO(2) and the mobilization of U(VI) from these solids in remediated subsurface environments, waste disposal sites, and natural uranium ores. PMID- 22304298 TI - Development of ELISA for the detection of transgenic vegetative insecticidal protein in GM crops/produce. AB - In the process of the development of insect-resistant genetically modified (GM) crops and also to evaluate the consistency in the expression of toxin under field conditions, immunological assays are commonly being used. An immunoassay was developed to support the labelling of vegetative insecticidal protein (Vip3A) based GM produce. The developed ELISA for the measurement of Vip3A is a triple antibody sandwich procedure utilising a polyclonal capture antibody (mouse anti Vip3A) and a polyclonal detection antibody (rabbit anti-Vip3A) followed by use of a third HRP-conjugated anti-species antibody (goat anti-rabbit IgG). The limit of detection limit of the ELISA assay was 16 ng ml(-1) with a linear quantification range from approximately 31 to 500 ng ml(-1) of Vip3A protein. Furthermore, the assay was in-house validated with GM brinjal samples. The assay was specific, sensitive and reproducible, which can be helpful to detect and track down the spread of unapproved and intentionally/unintentionally released GM produce harbouring Vip protein. PMID- 22304299 TI - Neuroimaging of pediatric intracranial infection--part 1: techniques and bacterial infections. AB - Conventional and advanced neuroimaging have become central to the diagnosis of infectious diseases of the pediatric central nervous system. Imaging modalities used by (pediatric) neuroradiologists include cranial ultrasound, computed tomography, and magnetic resonance imaging, including advanced techniques such as diffusion weighted or tensor imaging, perfusion weighted imaging, susceptibility weighted imaging, and (1) H magnetic resonance spectroscopy. In this first of a two part review, imaging techniques in general and the imaging findings of bacterial infections of the intracranial compartment including epidural empyema, subdural empyema, meningitis, cerebritis, cerebral abscess, and pyogenic intraventricular empyema (ventriculitis) are discussed. PMID- 22304301 TI - Do the myths still exist? Revisiting people's negative beliefs about organ donation upon death. AB - The prevalence of myths preventing people partial to donation in Australia from consenting is unknown. Respondents (N = 468: 381 donors, 26 non-donors, 61 undecided) were surveyed about their (negative) donation beliefs. Approximately 30% of donors were neutral or supported negative beliefs about organ allocation, especially donation to undesirable organ recipients and a black market organ trade. Confusion about brain death, lack of family and religious support, and discomfort with donation were negative beliefs endorsed by some respondents irrespective of donor preference. Proportionally, donors had greater trust in hospitals/doctors than other groups. Some myths still exist but may vary with donation preference. PMID- 22304300 TI - Serum IL-33 levels are associated with liver damage in patients with chronic hepatitis B. AB - This aim of this study was to assess the potential role of IL-33 in the pathogenic process of chronic hepatitis B (CHB). The levels of serum IL-33 and soluble ST2 (sST2) in CHB patients and healthy controls (HC) were determined using enzyme-linked-immunosorbent serologic assay, and the Th1 (IFN-gamma, TNF alpha, IL-2) and Th2 (IL-4, IL-6, IL-10) cytokines by cytometric bead array. It was found that the levels of serum IL-33 in CHB patients were significantly higher than that of HC at the base line, but decreased after treatment with adefovir dipivoxil for 12 weeks. The levels of serum sST2, as a decoy receptor of IL-33, were significantly higher in CHB patients than the HC. There was no correlation between the levels of serum sST2 and IL-33. The concentrations of serum Th1 (IFN-gamma, IL-2) and Th2 (IL-6, IL-10) cytokines in CHB patients significantly increased after treatment compared to the baseline. These results suggest that IL-33 is involved in the pathogenesis of CHB and that adefovir dipivoxil therapy can attenuate the production of IL-33 in patients with CHB. PMID- 22304302 TI - Three new steroidal glycosides from roots of Reineckia carnea. AB - Two new spirostanols and a new furostanol, reinocarnoside A (1), B (2) and C (3), were isolated from the roots of Reineckia carnea, together with two known compounds, (25S)-1beta,3beta,4beta-trihydroxyspirostan-5beta-yl-O-beta-D glucopyranoside (4), kitigenin-5beta-O-beta-D-glucopyranoside (5). The structures of three new compounds were elucidated by spectroscopic methods including 1-D NMR, 2-D NMR and MS spectrums, and their anticancer activities were evaluated by MTT method. PMID- 22304303 TI - Pyridine alkaloids from Senna multijuga as acetylcholinesterase inhibitors. AB - As part of an ongoing research project on Senna and Cassia species, five new pyridine alkaloids, namely, 12'-hydroxy-7'-multijuguinol (1), 12'-hydroxy-8' multijuguinol (2), methyl multijuguinate (3), 7'-multijuguinol (4), and 8' multijuguinol (5), were isolated from the leaves of Senna multijuga (syn. Cassiamultijuga). Their structures were elucidated on the basis of spectroscopic data analysis. Mass spectrometry was used for confirmation of the positions of the hydroxy groups in the side-chains of 1, 2, 4, and 5. All compounds exhibited weak in vitro acetylcholinesterase inhibitory activity as compared with the standard compound physostigmine. PMID- 22304305 TI - ArsH from the cyanobacterium Synechocystis sp. PCC 6803 is an efficient NADPH dependent quinone reductase. AB - The cyanobacterium Synechocystis sp. PCC 6803 possesses an arsenic resistance operon that encodes, among others, an ArsH protein. ArsH is a flavin mononucleotide (FMN)-containing protein of unknown function and a member of the family of NADPH-dependent FMN reductases. The nature of its final electron acceptor and the role of ArsH in the resistance to arsenic remained to be clarified. Here we have expressed and purified Synechocystis ArsH and conducted an intensive biochemical study. We present kinetic evidence supporting a quinone reductase activity for ArsH, with a preference for quinones with hydrophobic substituents. By using steady-state activity measurements, as well as stopped flow and laser-flash photolysis kinetic analyses, it has been possible to establish the mechanism of the process and estimate the values of the kinetic constants. Although the enzyme is able to stabilize the anionic semiquinone form of the FMN, reduction of quinones involves the hydroquinone form of the flavin cofactor, and the enzymatic reaction occurs through a ping-pong-type mechanism. ArsH is able to catalyze one-electron reactions (oxygen and cytocrome c reduction), involving the FMN semiquinone form, but with lower efficiency. In addition, arsH mutants are sensitive to the oxidizing agent menadione, suggesting that ArsH plays a role in the response to oxidative stress caused by arsenite. PMID- 22304307 TI - Glycan analysis by reversible reaction to hydrazide beads and mass spectrometry. AB - Investigation into glycoproteins and their associated glycans is the key to understanding the function of glycoproteins in biological pathways and disease development. Current methods for glycan analysis are generally based on multiple preparation processes to separate glycans from proteins and other molecules prior to analysis. During the multistep purification processes, glycans are continuously lost and the procedure increases the difficulty for accurate quantitative analysis of glycans. Here we describe the development of a novel technique, which uses hydrazide beads to capture glycans. It is based on the conjugation of glycans to hydrazide beads through the formation of reversible hydrazone, washing out unbound nonglycans, then releasing captured glycans by acids. The results showed that the glycans were able to be isolated from concatenate peptides by using hydrazide beads. This technique was also applied to the analysis of glycans from sera sample. The integrated capture-release on the solid-phase simplifies the procedure for glycan preparation from a complex mixture and can be a powerful tool for glycan analysis. PMID- 22304309 TI - [Priorities of secondary prevention of ischemic heart disease in conditions of a depressive region: preliminary results of the North Caucasian project]. AB - AIM OF THE STUDY: was detection of behavioral factors, main risk factors of development of cardiovascular diseases (CVD), assessment of adequacy of their management, as well as assessment of quality of life in a cohort of patients with ischemic heart disease from three republics of the North Caucasian region. METHODS: A sample of patients with ischemic heart disease (IHD) aged 40-69 years (n=1500) from 3 republics of the North Caucasian Federal Okrug (Ingushetia, Kabardino-Balkaria, and North Ossetia - Alania) were included in a clinico epidemiological project. In this work we present results obtained in three towns and districts of the Republic Ingushetia (300 men and 230 women with IHD and class II-III effort angina). Socio-demographic factors, family history of CVD, disturbances of nutrition, and physical activity were assessed by standard WHO questionnaires. For assessment of anthropometric deviations we measured height, body mass, and waist circumference. With the aim of detection of hyperlipidemia and disturbances of carbohydrate metabolism we measured levels of total cholesterol and fasting glucose in venous blood. Quality of life was assessed by EQ-5D questionnaire which comprised 5 points: movement, self service, everyday activity, pain/discomfort, and anxiety/depression. RESULTS: Each forth men (24.3%) smoked, and 12% were alcohol abusers. Each forth patient had severe disturbance of nutrition. Disturbances of nutrition of medium degree were detected twice more often. Way of life was sedentary in 63% of women and 46% of men. Abdominal obesity was detected in 46% of men and 72.6% of women. Prevalence of hypercholesterolemia was 96.7% among men and 90.7% among women. Every fifth patient with IHD had diabetes, in 10% of patients diabetes was newly detected. Quality of life changed in every second IHD patient with angina because of limitation in carrying out everyday work, movement and presence of chest discomfort, this was associated with presence of anxiety/depression. CONCLUSION: Main priority of secondary prevention in the Republic Ingushetia is adequate correction of hypercholesterolemia and arterial hypertension. However every forth patient requires complex therapy of 3-4 risk factors (hypercholesterolemia, hypertension, and/or diabetes, and/or smoking, and/or alcohol abuse). PMID- 22304310 TI - [Six months results of the Russian independent registry of acute coronary syndromes RECORD]. AB - In 6 months after inclusion into the Russian independent registry of patients with acute coronary syndromes (ACS) RECORD fate of 43% of participants (n=340) was elucidated by telephone contacts. After discharge after index hospitalization there were 15 deaths (4.8%) and 15 novel myocardial infarctions (MI) (4.8%). As expected patients who died or had MI compared with survivors were older, more often had signs of heart failure (Killip class more or equal II), and were less often prescribed aspirin and statins. Among patients with ST elevation ACS death rate between discharge and 6 months was lower among those subjected to primary PCI (7,7 vs 28,0%; =0,035). Important findings of the study were relatively low use of recommended by current guidelines treatments and high rate of cessation of prescribed at discharge medications. It was not possible basing on material of the study to exclude preferred use of active treatments in lower risk patients as a cause of better 6 months outcomes in more actively treated. PMID- 22304311 TI - [One-stage PCI of left main stenosis and infarct-related left main major branches in STEMI patients]. AB - AIMS: to determine immediate and long-term results, safety and efficacy of one stage PCI of LMCA and infarct-related LAD or CxA in STEMI. METHODS: 81 patients with STEMI treated with one-stage PCI of LMCA and infarct-related LAD or CxA were included into the study. LAD was infarct-related in 53 (65.4%) patients, circumflex (CxA) involved in 28 (34.6%) cases. Distal LMCA lesion was in 45 patients (55.6%). RESULTS: All patients were treated with drug-eluting stents. Radial access was used in 66 (81.4%) cases, in 38 (46.9%) patients intra-aortic balloon contrapulsation supported the procedure. IVUS was performed in 19 (23.4%) patients. Mortality during the procedure was 2.5% (2 patients with cardiogenic shock owing to infarct-related LAD). All other cases were technically successful. Two more patients died during the hospitalization, so short-term mortality was 4.9%. Angina symptoms persisted in 27 patients (33.3%) and were due to lesions in other coronary arteries. In these cases, the second PCI was performed. The mean follow-up period was 32-39 months. During follow-up 7 patients (8.6%) died due to various reasons. Target lesion revascularization was performed in 10 (12.3%) patients, including 3 repeated PCI of LMCA. Repeated revascularization due to atherosclerosis progression in other segments was done in 11 (13.5%) patients. MACCE-free survival was 60.7%. CONCLUSIONS: one-stage PCI of LMCA and infarct related LAD or CxA seems to be effective and safe treatment in patients with STEMI but larger studies with prolonged follow-up are needed. PMID- 22304312 TI - [Level of nitrous oxide in peripheral blood serum in patients with various severity of arterial hypertension]. AB - AIM: To elucidate the role of nitrous oxide (NO) in development of severe primary arterial hypertension (AH) including malignant hypertension and concomitant ischemic heart disease (IHD). MATERIAL AND METHOD: Patients with diagnosis of primary 1-3 degree AH (n=62, 21 men, 41 women aged 39-87 years, mean age 63.7+/ 2.7 years) and 28 subjects with normal arterial pressure (AP) (n=28, 13 men, 15 women aged 30-85 years, mean age 57.5+/-7.8 years). Blood serum levels of NO stable metabolites (nitrates and nitrites) were measured by reaction of their reduction in the presence of vanadium chloride and by reaction of diazotization of sulfanilamide by generated nitrite (modification by R.M.Miranda et al., 2001). RESULTS: NO level (level of its stable metabolites) was substantially elevated in patients with various severity of AH compared with subjects with normal AP. Severe and malignant course of AH was not associated with substantial lowering of NO level in blood serum. Relation between NO level and age found in subjects with normal AP, was not observed in patients with labile and stable course of AH. In patients with AH, normal serum NO level and signs of chronic involvement of cardiovascular system the disease was several times more often associated with atrial fibrillation and class II-III angina than in patients with high NO levels. Patients with AH combined with IHD more often had signs of heart failure and history of myocardial infarction. PMID- 22304313 TI - [Prevalence of atrial fibrillation among patients under observation by an outpatient clinic]. AB - Prevalence of atrial fibrillation among patients attending our policlinic (2.44 and 3.78% in 2002 and 2009, respectively) was higher among men than among women and progressively increased with age achieving maximum in the group of patients aged more or equal 85 years. Paroxysmal and persistent forms were more frequent than permanent AF. Thromboembolic complications, heart failure and valvular heart disease were to a greater degree characteristic of permanent AF. PMID- 22304314 TI - [The study of circulating endothelial precursor cells in patients with chronic heart failure]. AB - We examined 41 patients with ischemic heart disease (n=26) and dilated cardiomyopathy (DCM) (n=15). Control group comprised 15 practically healthy subjects. We found no substantial differences in the presence of CD34+CD133- and CD34+CD133-VEGFR-2+ cells in peripheral blood of patients with chronic heart failure (CHF) but noted lowering of level of CD34-CD133+VEGFR-2+ cells mainly in DCM group. Most significant factors determining lowering of number of circulating endothelial precursor cells (EPC) were age, level of low density lipoprotein cholesterol, and intima media thickness of common carotid arteries. We found lowering of colony forming ability of EPC in patients with CHF first of all in the group of patients with DCM. Abnormality of qualitative and quantitative composition of EPC can be considered as one of risk factors of endothelial dysfunction, pathological remodeling of cardiovascular system and CHF progression. PMID- 22304315 TI - [Calcification of valvular heart structures and calcified aortic stenosis in postmenopausal women]. PMID- 22304316 TI - [Possibilities of recanalization of chronic coronary occlusions with penetration catheter <>]. AB - Percutaneous coronary interventions (PCI) for chronic total occlusions (CTO) remain one of most difficult parts of interventional cardiology. Introduction of novel devices and methods of recanalization of CTO have facilitated fulfillment of these interventions and increased number of successful procedures. Howere a number of cases it is impossible to position a balloon in the site of occlusion even after its successful crossing with a guidewere. Penetration catheter Tornus was specifically created for such cases. It allows to form a channel in CTO for subsequent dilation and stent implantation. We present a review of available clinical studies assessing efficacy of the use of Tornus catheter during PCI for CTO, as well as results of its comparison with efficacy of rotational atherectomy. Authors of these studies concluded that Tornus catheter was highly effective in cases when it was not possible to pass a catheter for changing usual "RotaWire" guide with the aim of conducting rotational atherectomy, or in cases of impossibility to pass a balloon along a guidewere for predilation of the occlusion site. At the same time the use of penetration catheter had no advantages over rotational atherectomy. PMID- 22304317 TI - [Tissue engineering of heart valves: new opportunities and challenges]. AB - Replacement of heart valves appears to be prevailing method of surgical correction of end stage valvular heart defects. Main drawback of contemporary artificial valves is lack of growth, potential for remodeling, and inclination to degeneration. To overcome these limitations the modern science in the last decade focuses on tissue engineering of valves as an alternative to their prostheses. Basic idea of the technique is the use of decellularized xenogenic allogenic matrix or biopolymers seeded with autologous cells under special conditions created in bioreactor. This literature review is devoted to a novel direction in experimental cardiosurgery - tissue engineering of heart valves which in a unique way combines biological, engineering, and technological achievements. PMID- 22304318 TI - [Nephroprotection diabetes mellitus type 2: lessons from the ADVANCE trial]. AB - Based on the results of the ADVANCE study, the article considers the issues of medication nephroprotection in patients with type 2 diabetes mellitus, including patients with uncontrolled arterial hypertension. Potentials for use of fixed combination of perindopril + indapmide, which provides therapeutic effect at all stages of renal continuum, are discussed. It is established that improved control of blood pressure by combination of perindopril + indapmide leads to a significant decrease in mortality in DM 2 patients. PMID- 22304319 TI - [Atorvastatin for secondary prevention in patients with coronary artery disease]. PMID- 22304320 TI - [The use of polyunsaturated fatty acids in heart failure]. PMID- 22304321 TI - [Is there a future for thrombolytic therapy in acute coronary syndrome-segment elevation ST]. PMID- 22304322 TI - [Features of treatment of hypertension in patients with metabolic syndrome]. PMID- 22304323 TI - [The effectiveness of Ticagrelor does not depend on CYP2C19 gene polymorphism and ABCB1: results of a genetic analysis of the study PLATO]. PMID- 22304324 TI - [Echocardiography of cardiac cysts]. AB - Experience of ultrasound diagnosis of cardiac cysts of various origin accumulated by the authors during 30 years of practice is described. For the first time in the literature of this country and in foreign literature attention is attracted to a wide spectrum of possible cardiac cysts and there main diagnostic signs are presented. Eleven patients aged 9-55 years were examined. Intraoperative and histological verification of the described pathology was conducted. PMID- 22304325 TI - Full-color tuning of surface plasmon resonance by compositional variation of Au@Ag core-shell nanocubes with sulfides. AB - In the present study, we demonstrate the precise tuning of surface plasmon resonance over the full visible range by compositional variation of the nanoparticles. The addition of sulfide ions into the Au@Ag core-shell nanocubes generates stable Au@Ag/Ag(2)S core-shell nanoparticles at room temperature, and the plasmon extinction maximum shifts to the longer wavelength covering the entire visible range of 500-750 nm. Based on the optical property, the Au@Ag core shell nanocubes are employed as a colorimetric sensing framework for sulfide detection in water. The detection limit is measured to be 10 ppb by UV-vis spectroscopy and 200 ppb by naked eyes. Such nanoparticles would be useful for decoration and sensing purposes, due to their precise color tunability and high stability. PMID- 22304326 TI - Cooperative heteroassembly of the adenoviral L4-22K and IVa2 proteins onto the viral packaging sequence DNA. AB - Human adenovirus (Ad) is an icosahedral, double-stranded DNA virus. Viral DNA packaging refers to the process whereby the viral genome becomes encapsulated by the viral particle. In Ad, activation of the DNA packaging reaction requires at least three viral components: the IVa2 and L4-22K proteins and a section of DNA within the viral genome, called the packaging sequence. Previous studies have shown that the IVa2 and L4-22K proteins specifically bind to conserved elements within the packaging sequence and that these interactions are absolutely required for the observation of DNA packaging. However, the equilibrium mechanism for assembly of IVa2 and L4-22K onto the packaging sequence has not been determined. Here we characterize the assembly of the IVa2 and L4-22K proteins onto truncated packaging sequence DNA by analytical sedimentation velocity and equilibrium methods. At limiting concentrations of L4-22K, we observe a species with two IVa2 monomers and one L4-22K monomer bound to the DNA. In this species, the L4-22K monomer is promoting positive cooperative interactions between the two bound IVa2 monomers. As L4-22K levels are increased, we observe a species with one IVa2 monomer and three L4-22K monomers bound to the DNA. To explain this result, we propose a model in which L4-22K self-assembly on the DNA competes with IVa2 for positive heterocooperative interactions, destabilizing binding of the second IVa2 monomer. Thus, we propose that L4-22K levels control the extent of cooperativity observed between adjacently bound IVa2 monomers. We have also determined the hydrodynamic properties of all observed stoichiometric species; we observe that species with three L4-22K monomers bound have more extended conformations than species with a single L4-22K bound. We suggest this might reflect a molecular switch that controls insertion of the viral DNA into the capsid. PMID- 22304327 TI - The phytohormone auxin is a component of the regulatory system that controls UV mediated accumulation of flavonoids and UV-induced morphogenesis. AB - In plants, ultraviolet (UV)-B acclimation is a complex, dynamic process that plays an essential role in preventing UV-B damage to targets such as DNA and the photosynthetic machinery. In this study we tested the hypothesis that the phytohormone auxin is a component of the regulatory system that controls both UV mediated accumulation of flavonoids and UV-induced morphogenesis. We found that the leaf area of Arabidopsis thaliana Col-0 plants raised under a low dose of UV radiation (0.56 kJ m(-2) daily dose) was, on average, decreased by 23% relative to plants raised in the absence of UV-B, and this was accompanied by a decrease (P = 0.063) in free auxin in young leaf tissues. Compared to Col-0, both the auxin influx mutant axr4-1 and the auxin biosynthesis mutant nit1-3 displayed significantly stronger morphogenic responses, i.e. relative decreases in leaf area were greater for these two mutants. UV exposure also induced accumulation of flavonoids. In Col-0, increases in the concentrations of specific kaempferol derivatives ranged from 2.1- to 19-fold. Thus, UV induces complex changes in flavonoid-glycosylation patterns. Compared to Col-0, three auxin mutants displayed significantly different flavonoid profiles. Thus, based on mutant analysis, it is concluded that the phytohormone auxin plays a role in UV acclimation by regulating flavonoid concentration, flavonoid-glycosylation pattern and by controlling UV-induced morphogenic responses. PMID- 22304328 TI - Environmental friendly crush-magnetic separation technology for recycling metal plated plastics from end-of-life vehicles. AB - Metal-plated plastics (MPP), which are important from the standpoint of aesthetics or even performance, are increasingly employed in a wide variety of situations in the automotive industry. Serious environmental problems will be caused if they are not treated appropriately. Therefore, recycling of MPP is an important subject not only for resource recycling but also for environmental protection. This work represents a novel attempt to deal with the MPP. A self designed hammer crusher was used to liberate coatings from the plastic substrate. The size distribution of particles was analyzed and described by the Rosin Rammler function model. The optimum retaining time of materials in the crusher is 3 min. By this time, the liberation rate of the materials can reach 87.3%. When the density of the suspension is 31,250 g/m(3), the performance of liberation is the best. Two-step magnetic separation was adopted to avoid excessive crushing and to guarantee the quality of products. Concerning both the separation efficiency and grade of products, the optimum rotational speed of the magnetic separator is 50-70 rpm. On the basis of the above studies about the liberating and separating behavior of the materials, a continuous recycling system (the technology of crush-magnetic separation) is developed. This recycling system provides a feasible method for recycling MPP efficiently, economically, and environmentally. PMID- 22304329 TI - Cryoablation vs radiofrequency ablation for the treatment of renal cell carcinoma: a meta-analysis of case series studies. AB - Study Type - Therapy (systematic review). Level of Evidence 2b What's known on the subject? and What does the study add? The oncological success of partial nephrectomy in the treatment of small renal masses is well established. However, partial nephrectomy has largely supplanted the radical approach. In the last decade, laparoscopy has been adopted as the new surgical approach for the treatment of renal cell carcinoma. Laparoscopy offers the advantage of lower analgesic use, shorter hospital stay, and quicker recovery time. More recently, ablative technologies have been investigated as an alternative to laparoscopic partial nephrectomy. These techniques can often be performed percutaneously in the radiology suite, or laparoscopically without the need for hilar clamping. However, only the cryoablation and radiofrequency ablation modalities have had widespread use with several series reporting short to intermediate results. This review shows that both cryoablation and radiofrequency ablation are promising therapies in patients with small renal tumours (<4 cm), who are considered poor candidates for more involved surgery. OBJECTIVE: * To determine the current status of the literature regarding the clinical efficacy and complication rates of cryoablation vs radiofrequency ablation in the treatment of small renal tumours. METHODS: * A review of the literature was conducted. There was no language restriction. Studies were obtained from the following sources: MEDLINE, EMBASE and LILACS. * Inclusion criteria were (i) case series design with more than one case reported, (ii) use of cryoablation or radiofrequency ablation, (iii) patients with renal cell carcinoma and, (iv) outcome reported as clinical efficacy. * When available, we also quantified the complication rates from each included study. * Proportional meta-analysis was performed on both outcomes with a random-effects model. The 95% confidential intervals were also calculated. RESULTS: * Thirty-one case series (20 cryoablation, 11 radiofrequency ablation) met all inclusion criteria. * The pooled proportion of clinical efficacy was 89% in cryoablation therapy from a total of 457 cases. There was a statistically significant heterogeneity between these studies showing the inconsistency of clinical and methodological aspects. * The pooled proportion of clinical efficacy was 90% in radiofrequency ablation therapy from a total of 426 cases. There was no statistically significant heterogeneity between these studies. * There was no statistically significant difference regarding complications rate between cryoablation and radiofrequency ablation. CONCLUSIONS: * This review shows that both ablation therapies have similar efficacy and complication rates. * There is urgency for performing clinical trials with long-term data to establish which intervention is most suitable for the treatment of small renal masses. PMID- 22304332 TI - Comments regarding Practice Recommendations of the American Thyroid Association for radiation safety in the treatment of thyroid disease with radioiodine. PMID- 22304330 TI - Potential biomarkers in psychiatry: focus on the cholesterol system. AB - Measuring biomarkers to identify and assess illness is a strategy growing in popularity and relevance. Although already in clinical use for treating and predicting cancer, no biological measurement is used clinically for any psychiatric disorder. Biomarkers could predict the course of a medical problem, and aid in determining how and when to treat. Several studies have indicated that of candidate psychiatric biomarkers detected using proteomic techniques, cholesterol and associated proteins, specifically apolipoproteins (Apos), may be of interest. Cholesterol is necessary for brain development and its synthesis continues at a lower rate in the adult brain. Apos are the protein component of lipoproteins responsible for lipid transport. There is extensive evidence that the levels of cholesterol and Apos may be disturbed in psychiatric disorders, including autistic spectrum disorders (ASD). Here, we describe putative serum biomarkers for psychiatric disorders, and the role of cholesterol and Apos in central nervous system (CNS) disorders. PMID- 22304333 TI - Urban Latino school children's physical activity correlates and daily physical activity participation: a social cognitive approach. AB - Guided by Social Cognitive Theory (Bandura, 1986), this study investigated the relationships between urban Latino children's physical activity (PA) correlates and their daily PA levels. The participants were 120 Latino children recruited from an urban elementary school. They completed questionnaires assessing their PA correlates (self-efficacy, outcome expectancy, social support, and physical and social environmental factor) and their one-week PA levels were measured by accelerometers. Correlation and multiple regression analyses were performed to examine the relationships between children's PA correlates and daily PA levels. Correlation analyses indicated that children's self-efficacy, social support, and physical and social environmental factor were positively related to their PA levels. Regression analyses further yielded that children's self-efficacy and social support emerged as significant contributors of their daily PA levels. However, outcome expectancy and physical and social environmental factor failed to predict PA levels. The findings were discussed in regard to the implications for practice and areas for future research. PMID- 22304334 TI - War on the spore: Clostridium difficile disease among patients in a long-term acute care hospital. AB - The transmission of Clostridium difficile infection (CDI) is evident in healthcare facilities across the country and poses a risk for patients and communities. A comprehensive infection control program along with an active surveillance process was developed and implemented in a 50-bed long-term acute care hospital (LTACH) in the southeastern United States. Patients are admitted from surrounding hospitals, have an expected stay of at least 25 days, and are acutely ill. The majority of the patient population is ventilator dependent, immunocompromised, and treated with antimicrobials. The program, implemented in December 2009, utilized a tiered approach that included environmental cleaning and disinfection, diagnostics and surveillance, and infection control measures including antibiotic stewardship. The goal of this study was to decrease the incidence rate of CDI 15% by June 2010. Based upon year-end results, the facility achieved a 27.61% decrease in the CDI rate. During the following 12 months, the program continued to demonstrate sustainability resulting in a 23.0% decrease in the CDI rate. This program was successful in decreasing the incidence of CDI in the LTACH creating a safe and cost-effective environment for patients, families, and the community. PMID- 22304335 TI - A simple isocratic HPLC method for the simultaneous determination of bioactive components of Scutellariae radix extract. AB - Scutellariae Radix, the dried root of Scutellaria baicalensis Georgi, has been widely used in Asian countries for the treatment of dermatitis, diarrhoea, inflammatory disease and hepatic disease. A simple, sensitive and precise reversed-phase liquid chromatographic method with isocratic elution was developed to simultaneously determine four bioactive compounds in Scutellariae Radix: baicalein, baicalin, wogonin and wogonoside. Chromatographic analysis was performed on a YMC Pack Pro C(8) column (150 * 4.6 mm(2), 3 um), with a mobile phase of 0.1% formic acid : acetonitrile (70 : 30, v/v) at a flow rate of 1.0 mL min(-1), and UV detection at 280 nm. Linear behaviour was observed over the investigated concentration range (0.25-10 ug mL(-1)) for all analytes, with a correlation coefficient of >0.997. The intra- and inter-day precisions were <8.07%, and accuracies were 92.3-102.9%. This method was successfully applied for the analysis of marker compounds for the quality control of Scutellariae Radix extract. PMID- 22304337 TI - Burden of breast cancer with brain metastasis: a French national hospital database analysis. AB - OBJECTIVE: Incidence of breast cancer with brain metastases (BCBM) is increasing, especially among patients over-expressing HER2. Epidemiology on this sub-type of cancer is scarce, since cancer registries carry no information on the HER2 status. A retrospective database analysis was conducted to estimate the burden of BCBM, especially among HER2-positive patients in a secondary objective. METHODS: Patients with a new diagnosis of BCBM carried out between January and December 2008 were identified from the national hospital database using the International Disease Classification. Patients receiving a targeted anti-HER2 therapy were identified from the national pharmacy database. Hospital and pharmacy claims were linked to estimate the burden of HER2-positive patients. Data on hospitalizations were extracted to describe treatment patterns and healthcare costs during a 1 year follow-up. Predictors of treatment cost were analyzed through multi-linear regression analysis. RESULTS: Two thousand and ninety-nine BCBM patients were identified (mean age (SD) = 57.8 (13.6)), of whom 12.2% received a targeted anti HER2 therapy; 79% of patients had brain metastases associated with extracranial metastases, and the attrition rate reached 82%. Patients received mostly palliative care (47.4%), general medical care (40.6%), and chemotherapy (35.0%). The total annual hospital cost of treatment was 8,426,392?, representing a mean cost of 22,591? (+/-14,726) per patient, mainly influenced by extracranial metastases, surgical acts, and HER2-overexpression (p < 0.0001). CONCLUSIONS: The database linkage of hospital and pharmacy claims is a relevant approach to identify sub-type of cancer. Chemotherapy was widely used as a systemic treatment for breast cancer rather than for local treatment of brain metastases whose morbi mortality remains high. The variability of treatment costs suggests clinical heterogeneity and, thus, extensive individualization of protocols. PMID- 22304338 TI - Cost-effectiveness of several atypical antipsychotics in orally disintegrating tablets compared with standard oral tablets in the treatment of schizophrenia in the United States. AB - OBJECTIVE: Although the use of innovative drug delivery systems, like orally disintegrating antipsychotic tablets (ODT), may facilitate medication adherence and help reduce the risk of relapse and hospitalization, no information is available about the comparative cost-effectiveness of standard oral tablets (SOT) vs ODT formulations in the treatment of schizophrenia. This study compared the cost-effectiveness of olanzapine ODT and olanzapine SOT in the usual treatment of outpatients with schizophrenia from a US healthcare perspective. The study also compared olanzapine ODT with risperidone and aripiprazole, two other atypical antipsychotics available in both ODT and SOT formulations. METHODS: Published medical literature and a clinical expert panel were used to populate a 1-year Monte Carlo Micro-simulation model. The model captures clinical and cost parameters including adherence levels, treatment discontinuation by reason, relapse with and without inpatient hospitalization, quality-adjusted life years (QALYs), treatment-emergent adverse events, healthcare resource utilization, and associated costs. Key outcomes were total annual direct cost per treatment, QALY, and incremental cost-effectiveness (ICER) per 1 QALY gained. RESULTS: Based on model projections, olanzapine ODT therapy was more costly ($9808 vs $9533), but more effective in terms of a lower hospitalization rate (15% vs 16%) and better QALYs (0.747 vs 0.733) than olanzapine SOT therapy. Olanzapine ODT was more cost effective than olanzapine SOT (ICER: $19,643), more cost-effective than risperidone SOT therapy (ICER: $39,966), and dominant (meaning less costly and more effective) than risperidone ODT and aripiprazole in ODT or SOT formulations. LIMITATIONS: Lack of head-to-head randomized studies comparing the three studied atypical antipsychotics required making input assumptions that need further study. CONCLUSIONS: This micro-simulation found that the utilization of olanzapine ODT for the treatment of schizophrenia is predicted to be more cost effective than any other ODT or SOT formulations of the studied atypical antipsychotic medications. PMID- 22304339 TI - "Not ready to sort it yet": revised reinforcement sensitivity theory (rRST) predicts left-handed behavioural inhibition during a manual sorting task. AB - Wright, Hardie, and Rodway (2004) showed that left-handers were slower to respond initially to the Tower of Hanoi, and proposed that this was due to either anxious or inhibited behaviour in their approach or to right hemisphere superiority in spatial tasks. The revised reinforcement sensitivity theory (Gray & McNaughton, 2000) offers a rationale for the influence of anxiety, and Wright, Hardie, and Wilson (2009) demonstrated a behavioural inhibition system (BIS) difference related to handedness, arguing that, due to their increased BIS sensitivity, left handers may show more anxiety-induced goal conflict and should take longer to initiate any novel task. On the basis of this, the current study tested the prediction of increased left-handed inhibition of action, using a manual sorting task. A total of 78 participants took part and analyses revealed that left handers took significantly longer to move the first card. A significant handedness*sex interaction was found for task completion time. The significant initiation difference further supports the idea that rBIS sensitivity differences may be the source of divergent responses in novel tasks, rather than hemispheric dominance related withdrawal (Davidson, 1995), and provides support for the new role of BIS in the revised rather than original reinforcement sensitivity theory (Gray, 1982). PMID- 22304342 TI - Quantitative mass spectrometry combined with separation and enrichment of phosphopeptides by titania coated magnetic mesoporous silica microspheres for screening of protein kinase inhibitors. AB - We describe herein the development of a matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS) approach for screening of protein kinase inhibitors (PKIs). MS quantification of phosphopeptides, the kinase-catalyzed products of nonphosphorylated substrates, is a great challenge due to the ion suppression effect of highly abundant nonphosphorylated peptides in enzymatic reaction mixtures. To address this issue, a novel type of titania coated magnetic hollow mesoporous silica spheres (TiO(2)/MHMSS) material was fabricated for capturing phosphopeptides from the enzymatic reaction mixtures prior to MS analysis. Under optimized conditions, even in the presence of 1000-fold of a substrate peptide of tyrosine kinase epidermal growth factor receptor (EGFR), the phosphorylated substrates at the femtomole level can be detected with high accuracy and reproducibility. With a synthetic nonisotopic labeled phosphopeptide, of which the sequence is similar to that of the phosphorylated substrate, as the internal standard, the MS signal ratio of the phosphorylated substrate to the standard is linearly correlated with the molar ratio of the two phosphopeptides in peptide mixtures over the range of 0.1 to 4 with r(2) being 0.99. The IC(50) values of three EGFR inhibitors synthesized in our laboratory were then determined, and the results are consistent with those determined by an enzyme-linked immunosorbent assay (ELISA). The developed method is sensitive, cost/time-effective, and operationally simple and does not require isotope/radioative-labeling, providing an ideal alterative for screening of PKIs as therapeutic agents. PMID- 22304344 TI - Cytotoxic angucycline class glycosides from the deep sea actinomycete Streptomyces lusitanus SCSIO LR32. AB - Five new C-glycoside angucyclines, named grincamycins B-F (1-5), and a known angucycline antibiotic, grincamycin (6), were isolated from Streptomyces lusitanus SCSIO LR32, an actinomycete of deep sea origin. The structures of these compounds were elucidated on the basis of extensive spectroscopic analyses, including MS and 1D and 2D NMR experiments. All compounds except grincamycin F (5) exhibited in vitro cytotoxicities against the human cancer cell lines HepG2, SW-1990, HeLa, NCI-H460, and MCF-7 and the mouse melanoma cell line B16, with IC50 values ranging from 1.1 to 31 MUM. PMID- 22304346 TI - [Factors determining prognosis of patients with stable ischemic heart disease (results of a five years prospective study)]. AB - Risk stratification seems to be very important in patients with stable coronary artery disease (CAD). However, the prognostic scales are now available only for the early risk assessment in patients with acute coronary syndromes and in patients undergoing percutaneous coronary interventions. Aim of the study was to assess the frequency of cardiovascular events (CVE) during 5 years of follow-up in patients with stable CAD and to construct a long-term risk prediction model for these patients. 503 patients (mean age 59.4 years) were included in the study. The follow-up period ranged between 3.0 and 7.5 years (mean 5.0 years). Main end points were fatal and non-fatal cardiovascular events: cardiovascular death, acute coronary syndromes, ischemic stroke, transient ischemic attack, peripheral arterial thrombosis, and need for revascularization in any affected vascular area. Total frequency of events was 31.0% (5.7/100 patient years). Independent predictors of events were: severity of angina, three vessel coronary disease, previous myocardial infarction, previous stroke/ transient ischemic attack, peripheral arterial disease, obesity, chronic kidney disease and history of erosive gastritis. The presence of more or equal 3 risk factors was significantly associated with increased frequency of CVE. PMID- 22304347 TI - [Efficacy of ivabradine in patients with stable angina and comorbid chronic obstructive pulmonary disease]. AB - We investigated impact of ivabradine on exercise capacity and quality of life in patients with stable angina and comorbid chronic obstructive pulmonary disease during treatment with -blockers. Ivabradine with -blockers reduced heart rate, increased exercise capacity and improved angina more effective than -blockers only. Quality of life associated with angina increased in patients with stage I and II chronic obstructive pulmonary disease. Addition of ivabradine to blockers for 2 month did not produce adverse respiratory effects. PMID- 22304348 TI - [Assessment of psychological status of patients with effort angina]. AB - AIM: Assessment of psychological status including levels of anxiety and depression as well as susceptibility to chronic stress of men and women with ischemic heart disease (IHD) and effort angina. MATERIAL AND METHODS: We included in this study 530 patients with IHD and functional class I+/-III effort angina (300 men, mean age 54+/-0,4 years and 230 women, mean age 55,7+/-0,5 years). We used the Reeder questionnaire for assessment of susceptibility to chronic stress, and hospital HADS score for analysis of anxiety and depression. RESULTS: Just 22% of patients had low level of stress while in 58.5% and 19.5% level of stress was medium and high, respectively. High stress was more often noted among men (22,3%) compared with women (15,7%). However this difference was not statistically significant. Overall 82 and 72% of men and 79 and 71% of women had various degrees of depression and anxiety, respectively. Depression and anxiety were clinically manifested in 38 and 42% of patients. There was no statistically significant difference in depression and anxiety rates between men and women. CONCLUSIONS: According to questionnaire data psychological status of patients with IHD was characterized by susceptibility to high and medium chronic stress as well as by subclinical and clinical anxiety and depression. There were no significant differences in rates of psychosomatic disturbances between men and women with IHD. Each forth patient required professional correction of derangements of psychological status. PMID- 22304349 TI - [Level of glycemia as a marker of prognosis in patients with myocardial infarction with ST segment elevation]. AB - High mortality of patients with myocardial infarction (MI) determines pursuit of novel markers of risk as well as predictors of development of unfavorable outcome. The question of the role glycemia in development of cardiovascular complications in patients with acute coronary syndrome remains open. Analysis of in hospital mortality revealed U-shaped relacion ship between level of glycemia at admission and mortality in patients with ST elevation MI combined with diabetes mellitus (DM), and presence of direct linear relation - in patients without DM. Episodes of hypoglycemia registered in patients with MI and DM at hospital stage of treatment do not determine in hospital prognosis, but allow to distinguish a group of patients with unfavorable course of remote postinfarction period. PMID- 22304350 TI - [Combined low-dose antihypertensive therapy in pregnant women with hypertension and preeclampsia]. AB - The effect of low-dose combination antihypertensive therapy in fixed form, containing 2.5 mg of bisoprolol and 6.25 mg of hydrochlorothiazide, the clinical condition, the daily profile of blood pressure, body adrenoreactivity structural and functional parameters of the left ventricle in 28 pregnant women with preeclampsia in the background chronic hypertension (hypertension stage II, 2 nd degree) and 28 pregnant women with preeclampsia and mild to moderate severity in terms of 22-28 weeks of pregnancy. After 16 weeks of receiving a fixed form, containing 2.5 mg of bisoprolol and 6.25 mg hydrochlorothiazide, the target BP level reached 76% of pregnant women with preeclampsia with chronic hypertension and 81% - with preeclampsia. In both groups, the parameters are optimized daily profile of blood pressure, the value of the total peripheral vascular resistance. PMID- 22304351 TI - [Newly developed atrial fibrillation among patients under active observation by an outpatient clinic]. AB - We carried out prospective cohort study of incidence of new cases of atrial fibrillation (AF) in a sample of Moscow population (patients under observation in our policlinic). Total incidence of AF between 2003 and 2009 was 7.7 per 1000 patient/years, it was higher among men than among women. Incidence of AF progressively increased with age reaching maximum in age group more or equal 85 years. Most frequent baseline disease in patients with first appearance of AF was hypertensive disease (71%). Ischemic heart disease diagnosed according to strict criteria (postinfarction cardiosclerosis, revascularization procedures) was registered in 20.1%, diabetes - in 15.7%, chronic heart failure - in 13%, valvular heart disease - in 5.6%, and history of acute ischemic stroke - in 2.5% of patients. PMID- 22304352 TI - [Pharmacoeconomic analysis of dabigatran etexilate effectiveness in patients with nonvalvular atrial fibrillation]. PMID- 22304353 TI - [Two years experience of the use of a penetration catheter (Tornus) recanalization during percutaneous coronary interventions on chronic total occlusions]. AB - We included in this study 43 patients chronic total occlusions (CTO) subjected percutaneous coronary interventions (PCI) with the use of penetration catheter (Tornus) in 2009-2010. Penetration catheter was applied only in those cases when it was not possible to introduce low profile coronary dilatation catheter into the site of occlusion. After penetration of CTO by a guide wire a channel was formed by a manually rotated penetration catheter. The Tornus catheter was successfully passed into distal part of an artery in 81.4% of cases. In other. PMID- 22304354 TI - [Left main coronary artery stenosis and progression of coronary artery atherosclerosis after angioplasty and stenting in patients directed to coronary artery bypass surgery]. AB - Recent investigations demonstrated appearance of left main coronary artery stenosis after PTCA. We performed a retrospective study of specific characteristics of development of coronary lesions after percutaneous coronary interventions (PCI) in patients subjected to coronary artery bypass grafting (CABG) because of angina recurrence after PCI. Data of 150 patients operated because of angina recurrence after PCI were analyzed. The recurrence of angina in 93% of cases was associated with development of significant stenoses in previously intact segments of coronary arteries, but not with restenosis or occlusion of the stented segment. The recurrence of symptoms occurred in 1 year after coronary stenting in 54% of patients. In 19 patients rapid development of a novel left main coronary artery stenosis was observed. Some characteristics of this group (the use of Back-up, XB, AL-catheters, repetitive PCI, manipulations in more than 2 coronary segments, stenting of bifurcations with 2 stents, use of kissing-balloons, small diameter of left coronary artery, and concomitant diabetes) significantly differed from those of the main group. In all patients CABG was successful. PMID- 22304355 TI - [Long-term results of vascular surgery of Lerish syndrome in patients with type II diabetes Mellitus]. AB - We analyzed long-term results of vascular surgery in 199 patients with diabetes and chronic limb ischemia. At the time of the study mean age of patients was 64.7+1.2 years. They all had severe course of disease. Results showed that in the majority of patients good clinical effect after aorto-femoral reconstructions persisted over a long period of time. Patency of aorto-femoral bypass and limb salvage rate after 9 years equaled 72 and 79%, respectively. This was associated with improved quality of life. Surgery for severe limb ischemia (50 % of patients had critical ischemia) helped to preserve the limb and achieve sustainable increase of pain-free walking distance in 85 % of patients. However 5-year survival rate was 75%. The leading cause of death was myocardial infarction. This was indicative of the lack of prevention of progression of coronary artery disease. Thus, despite the presence of diabetes aorto-femoral reconstructions in most patients reliably and continuously prevented development of critical ischemia and preserved lower limbs. Active prophylaxis of cardiac complications is necessary for improvement of long-term survival of patients after vascular reconstructive surgery. PMID- 22304356 TI - [Prognostic value of creatine kinase MB-fraction and TroponinT increase in patients after coronary bypass grafting (data of 3-year prospective observation)]. AB - The aim of this work was to investigate prognostic value of creatine kinase MB fraction and troponin T increase in patients after coronary bypass grafting (during 3-year prospective observation). Parameters were studied in 6, 12, 48 and 72 hours after surgical myocardial revascularization. It was revealed that increase of myocardial necrosis markers is associated with significant more frequent development of cardiovascular complications during 3-year prospective observation. PMID- 22304357 TI - [Comparative evaluation of antiplatelet efectiveness drugs of original and reproduced enteric forms of acetylsalicylic acid (clinical study ICAR))]. AB - The purpose of the study was a comparative study of antiplatelet activity of acetylsalicylic acid drugs, produced in gastro-resistant form trombopol 75 mg and aspirin cardio 100 mg in patients with high risk of cardiovascular events. Effect of trombopol 75 mg versus 100 mg aspirin cardio on platelet aggregation in 30 patients with high risk of cardiovascular events during 3 week treatment period was studied. Design method: blind, randomized, crossover method. Three weeks before the initial therapy, for those patients, who received antiplatelet platelet therapy at the time of inclusion in the study, this therapy was withdrew ("wash-out period"), after which patient was given one of the study drug (sequence of courses was s determined according to the scheme of randomization) with the recommendation of taking it daily in the morning at the same time. At each visit, before the next dose of the drug, blood samples for determination of ADP-induced platelet aggregation were taken, physical examination, measurement of blood pressure (BP) and heart rate were recorded, adverse events were recorded. Follow-up visit was performed 3 weeks later. 21 days after first study drug withdrawal, a second similar course of therapy with another drug was performed. Antiplatelet efficacy of aspirin was assessed by its effect on spontaneous and ADP- induced platelet aggregation. Aggregation activity was determined by turbidometric method by changing of translucent ability of the blood sample during the formation of aggregates after 2 minutes of exposure. As an inducer of aggregation ADP solutions of three concentrations (0.5, 1 and 2 mM) were used. No significant difference between compared drugs in influence on aggregation ability of platelets after 3 weeks of daily intake was found. No adverse events associated with taking of studied drugs were registered. It was concluded that, generic APD - trombopol 75 mg and aspirin cardio 100 mg were equivalent on antiplatelet efficacy and tolerability. PMID- 22304358 TI - [The SHIFT study: a shift in a correct direction]. PMID- 22304359 TI - [Hypertensive crisis in cardiology: place of urapidil]. PMID- 22304360 TI - [Glycogen storage disease: danon syndrome]. PMID- 22304361 TI - In situ monitoring of atomic layer deposition in nanoporous thin films using ellipsometric porosimetry. AB - Ellipsometric porosimetry (EP) is a handy technique to characterize the porosity and pore size distribution of porous thin films with pore diameters in the range from below 1 nm up to 50 nm and for the characterization of porous low-k films especially. Atomic layer deposition (ALD) can be used to functionalize porous films and membranes, e.g., for the development of filtration and sensor devices and catalytic surfaces. In this work we report on the implementation of the EP technique onto an ALD reactor. This combination allowed us to employ EP for monitoring the modification of a porous thin film through ALD without removing the sample from the deposition setup. The potential of in situ EP for providing information about the effect of ALD coating on the accessible porosity, the pore radius distribution, the thickness, and mechanical properties of a porous film is demonstrated in the ALD of TiO(2) in a mesoporous silica film. PMID- 22304362 TI - Positional effects of phosphorylation on the stability and morphology of tau related amyloid fibrils. AB - Hyperphosphorylated forms of tau protein are the main component of paired helical filaments (PHFs) of neurofibrillary tangles in the brain of Alzheimer's disease patients. To understand the effect of phosphorylation on the fibrillation of tau, we utilized tau-derived phosphorylated peptides. The V(306)QIVYK(311) sequence (PHF6) in the microtubule-binding domain is known to play a key role in the fibrillation of tau, and the short peptide corresponding to the PHF6 sequence forms amyloid-type fibrils similar to those generated by full-length tau. We focused on the amino acid residue located at the N-terminus of the PHF6 sequence, serine or lysine in the native isoform of tau, and synthesized the PHF6 derivative peptides with serine or lysine at the N-terminus of PHF6. Peptides phosphorylated at serine and/or tyrosine were synthesized to mimic the possible phosphorylation at these positions. The critical concentrations of the fibrillation of peptides were determined to quantitatively assess fibril stability. The peptide with the net charge of near zero tended to form stable fibrils. Interestingly, the peptide phosphorylated at the N-terminal serine residue exhibited remarkably low fibrillation propensity as compared to the peptide possessing the same net charge. Transmission electron microscopy measurements of the fibrils visualized the paired helical or straight fibers and segregated masses of the fibers or heterogeneous rodlike fibers depending on the phosphorylation status. Further analyses of the fibrils by the X-ray fiber diffraction method and Fourier transform infrared spectroscopic measurements indicated that all the peptides shared a common cross-beta structure. In addition, the phosphoserine-containing peptides showed the characteristics of beta-sandwiches that could interact with both faces of the beta-sheet. On the basis of these observations, possible protofilament models with four beta-sheets were constructed to consider the positional effects of the serine and/or tyrosine phosphorylations. The electrostatic intersheet interaction between phosphate groups and the amino group of lysine enhanced the lateral association between beta-sheets to compensate for the excess charge. In addition to the previously postulated net charge of the peptide, the position of the charged residue plays a critical role in the amyloid fibrillation of tau. PMID- 22304363 TI - Early cleaved bovine embryos show reduced incidence of chromosomal aberrations and higher developmental potential on day 4.5 post-insemination. AB - The present study aimed to investigate whether the timing of the first zygotic cleavage (FZC) influences the speed of embryo development expressed by the total cell count and the rate of chromosomally aberrant embryos. Bovine embryos were produced in vitro and divided into two categories according to the timing of FZC: early cleavers (at 30 hpi; EC) and non-early cleavers (at 48 hpi; NEC). On day 4.5 pi, embryos were grouped into three classes depending on the number of blastomeres: delayed (<8 BL), normal (8-16 BL) and advanced (>16 BL). We applied fluorescence in situ hybridization (FISH) with probes for bovine chromosomes 6 and X. The only form of chromosomal imbalance observed was mixoploidy [(2n/3n; 2n/4n); 19.9%, 54/271]. Early cleavers were less often chromosomally unbalanced (13.9%, 20/144) than their NEC counterparts (26.7%, 34/127). Among embryos developing at a normal speed, the NEC embryos were more often abnormal (NEC 20/80; EC 10/79; p < 0.05). The advanced embryos were not observed among the NEC category, whereas such embryos from EC category displayed no chromosomal aberrations. The majority of embryos arrested at the 8 BL stage were of NEC category and were carriers of chromosomally abnormal blastomeres. With regard to embryonic sex, we demonstrated that although males dominate among bovine embryos developing in vitro, the incidence of mixoploidy was equal for both sexes. It can be suggested that a good-quality bovine embryo is usually an early cleaver that develops at higher speed and contains less aberrant cells. The present study also confirmed the usefulness of the FZC as a marker of embryo quality by demonstrating a significantly lower incidence of aberrations in early embryos. PMID- 22304364 TI - Classification of episiotomy: towards a standardisation of terminology. AB - Seven episiotomy incisions are described in the literature, although only midline, mediolateral or lateral episiotomies are commonly used. Recent research has demonstrated variations in both site and direction of the incision, and differences between the angle of incision at the time of crowning of the fetal head and the angle of the scar once the wound has been repaired. We review this evidence and suggest that this variation may undermine the reliability of much published work. We suggest a standardised definition of each type of episiotomy to establish uniformity going forward, so that future studies are amenable to comparison and meta-analysis. PMID- 22304365 TI - A logistic model for the detection of circulating tumour cells in human metastatic colorectal cancer. AB - The accuracy in the diagnosis of metastatic colorectal cancer (mCRC) represents one of the challenges in the clinical management of patients. The detection of circulating tumour cells (CTC) is becoming a promising alternative to current detection techniques, as it focuses on one of the players of the metastatic disease and it should provide with more specific and sensitive detection rates. Here, we describe an improved method of detection of CTC from mCRC patients by combining immune-enrichment, optimal purification of RNA from very low cell numbers, and the selection of accurate PCR probes. As a result, we obtained a logistic model that combines GAPDH and VIL1 normalized to CD45 rendering powerful results in the detection of CTC from mCRC patients (AUROC value 0.8599). We further demonstrated the utility of this model at the clinical setting, as a reliable prognosis tool to determine progression-free survival in mCRC patients. Overall, we developed a strategy that ameliorates the specificity and sensitivity in the detection of CTC, resulting in a robust and promising logistic model for the clinical management of metastatic colorectal cancer patients. PMID- 22304366 TI - UV responses of Lolium perenne raised along a latitudinal gradient across Europe: a filtration study. AB - Lolium perenne (cv. AberDart) was grown at 14 locations along a latitudinal gradient across Europe (37-68 degrees N) to study the impact of ultraviolet radiation (UV) and climate on aboveground growth and foliar UV-B absorbing compounds. At each location, plants were grown outdoors for 5 weeks in a replicated UV-B filtration experiment consisting of open, UV-B transparent (cellulose diacetate) and UV-B opaque (polyester) environments. Fourier transform infrared spectroscopy was used to compare plant metabolite profiles in relation to treatment and location. UV radiation and climatic parameters were determined for each location from online sources and the data were assessed using a combination of anova and multiple regression analyses. Most of the variation in growth between the locations was attributable to the combination of climatic parameters, with minimum temperature identified as an important growth constraint. However, no single environmental parameter could consistently account for the variability in plant growth. Concentrations of foliar UV-B absorbing compounds showed a positive trend with solar UV across the latitudinal gradient; however, this relationship was not consistent in all treatments. The most striking experimental outcome from this study was the effect of presence or absence of filtration frames on UV-absorbing compounds. Overall, the study demonstrates the value of an European approach in studying the impacts of natural UV across a large latitudinal gradient. We have shown the feasibility of coordinated UV filtration at multiple sites but have also highlighted the need for open controls and careful interpretation of plant responses. PMID- 22304367 TI - Spitz nevus arising upon a congenital glomuvenous malformation. AB - There are several reports of the collision of vascular and pigmentary anomalies (e.g., phakomatosis pigmentovascularis) and the association between congenital melanocytic nevi and infantile hemangiomas. We report a case of Spitz nevus arising in skin overlying a congenital plaque-like glomuvenous malformation (GVM). This is the first report of a Spitz nevus arising in direct contiguity to a GVM. PMID- 22304368 TI - Organophosphate pesticide exposure and neurodevelopment in young Shanghai children. AB - A large amount of organophosphate pesticides (OPs) is used throughout China. Animal studies have suggested that even moderate doses are toxic to neurodevelopment, but there are a few studies in humans. We investigated both the urinary levels of OP metabolites in children and their relationship with child neurodevelopment. Participating 301 young children (23-25 months of age) were recruited from two community hospitals in Shanghai between February and October 2008. We measured five nonspecific dialkyl phosphate (DAP) metabolite levels of OPs in the children's urine and examined their association with the children's developmental quotients (DQs) based on the Gesell Developmental Schedules (GDS). The creatinine-adjusted geometric means (GMs) of OP metabolites in urine samples were 11.27 MUg/g for DMP; 6.99 MUg/g for DMTP; 7.96 MUg/g for DEP; 14.19 MUg/g for DETP; and 4.55 MUg/g for DEDTP. The children had relatively higher levels of OP urinary metabolites compared with those reported in developed countries, no association was found between child urinary levels of OP metabolites and any of the DQ scores. However, our results should be interpreted with caution, and more studies of children living in China are warranted given the relatively high levels of child OP urinary metabolites in Shanghai. PMID- 22304369 TI - Evaluation of candidate diagnostic microRNAs in thyroid fine-needle aspiration biopsy samples. AB - BACKGROUND: Thyroid cancer diagnosis in the United States has increased by 2.3 folds in the last three decades. Up to 30% of thyroid fine-needle aspiration biopsy (FNAB) results are inconclusive. Several differentially expressed microRNAs (miRNAs) have been identified as candidate diagnostic markers for thyroid nodules. We hypothesized that these differentially expressed miRNAs may improve the accuracy of FNAB in difficult to diagnose thyroid nodules. METHODS: Expression levels of four miRNAs (miR-7, -126, -374a, and let-7g) were analyzed using quantitative real-time reverse transcription-polymerase chain reaction in 95 FNAB samples as the training set. A predictor model was formulated based on the most differentially expressed miRNA (miR-7) DeltaCt value and the model was applied on a separate cohort of 59 FNAB samples as the validation set. RESULTS: miR-7 was the best predictor to distinguish benign from malignant thyroid FNAB samples. The other three miRNAs were co-expressed and did not significantly contribute to the predictor model. miR-7 had a sensitivity of 100%, specificity of 29%, positive predictive value (PPV) of 36%, negative predictive value (NPV) of 100%, and overall accuracy of 76% when applied to the validation set. In subgroup analysis of preoperative nondiagnostic, indeterminate, or suspicious FNAB samples, the predictor model had an overall accuracy of 37% with sensitivity of 100%, specificity of 20%, PPV of 25%, and NPV of 100%. CONCLUSIONS: miR-7 may be a helpful adjunct marker to thyroid FNAB in tumor types which are inconclusive. Given the high NPV of miR-7, a patient with a benign result based on the predictor model may be followed as opposed to performing an immediate diagnostic thyroidectomy. Future prospective clinical trials evaluating its accuracy in a larger cohort are warranted to determine its clinical utility. PMID- 22304370 TI - Enhancing Braden pressure ulcer risk assessment in acutely ill adult veterans. AB - This study sought to determine if a parsimonious pressure ulcer (PU) predictive model could be identified specific to acute care to enhance the current PU risk assessment tool (Braden Scale) utilized within veteran facilities. Factors investigated include: diagnosis of gangrene, anemia, diabetes, malnutrition, osteomyelitis, pneumonia/pneumonitis, septicemia, candidiasis, bacterial skin infection, device/implant/graft complications, urinary tract infection, paralysis, senility, respiratory failure, acute renal failure, cerebrovascular accident, or congestive heart failure during hospitalization; patient's age, race, smoking status, history of previous PU, surgery, hours in surgery; length of hospitalization, and intensive care unit days. Retrospective chart review and logistic regression analyses were used to examine Braden scores and other risk factors in 213 acutely ill veterans in North Florida with (n = 100) and without (n = 113) incident PU from January-July 2008. Findings indicate four medical factors (malnutrition, pneumonia/pneumonitis, candidiasis, and surgery) have stronger predictive value (sensitivity 83%, specificity 72%, area under receiver operating characteristic [ROC] curve 0.82) for predicting PUs in acutely ill veterans than Braden Scale total scores alone (sensitivity 65%, specificity 70%, area under ROC curve 0.70). In addition, accounting for four medical factors plus two Braden subscores (activity and friction) demonstrates better overall model performance (sensitivity 80%, specificity 76%, area under ROC curve 0.88). PMID- 22304371 TI - Method for simultaneous determination of partition coefficients for cyclic volatile methylsiloxanes and dimethylsilanediol. AB - Cyclic volatile methyl siloxanes (cVMS) such as octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), and dodecamethylcyclohexasiloxane (D6) may enter the environment through industrial activities and the use of various consumer products. Reliable air/water (K(AW)), 1-octanol/water (K(OW)), and octanol/air partition coefficients (K(OA)) for those compounds and their common degradation product, dimethylsilanediol, are critical for accurate prediction of the environmental fate, distribution, and transport of these materials. Challenges have been encountered in determining these properties for cVMS and their degradation products mainly due to the extremely low water solubility of the organosiloxanes, low volatility of their degradation products, and reactivity of those compounds in the water/1-octanol system that can lead to inconsistent and inaccurate partition coefficients. A novel direct method is presented for the simultaneous determination of K(AW), K(OW), and K(OA) of organic compounds and was applied to these organosilicon compounds. It was tested in a range of log K(AW) values from -6.8 to 3.1, log K(OW) values from -0.4 to 8.9, and log K(OA) values up to 7. The advantages of the new direct method include the improved accuracy, a shortened measurement time, simultaneous measurement of three partition coefficients of multiple compounds, self-consistency among resultant partition coefficients, and a wide range of applicability including materials that may be slowly reactive in the water/1-octanol system. PMID- 22304373 TI - Vertical representational biases in healthy university students. AB - In line bisection tasks neurologically intact individuals tend to bisect lines slightly left of their midpoint for horizontal lines, and above centre for vertical lines, a phenomenon known as perceptual pseudoneglect (Bowers & Heilman, 1980; Van Vugt, Fransen, Creten, & Paquiner, 2000). Recent investigations have demonstrated the leftward bias to extend to mental imagery, a finding known as representational pseudoneglect (McGeorge, Beschin, Colnaghi, Rusconi, & Della Sala, 2007). This paper examined whether the upward bias found in perceptual tasks extended to mental imagery in healthy individuals. University students studied a diagram depicting a central character and target objects that were located in six positions relative to the person in the diagram (left/right, up/down, and front/back). Following learning, participants recalled the locations of the objects from several imagined orientations. Performance on the recall task revealed faster response latencies for upward targets, providing evidence for vertical representational biases in healthy individuals. PMID- 22304374 TI - Lay health workers and HIV care in rural Lesotho: a report from the field. AB - Lay health workers (LHWs) are individuals who participate in a variety of health services, even though they have no formal professional training. They have been used in a variety of settings, especially where health care needs outstrip available human resources. Lesotho faces a severe human resource shortage as it attempts to manage its HIV pandemic, with more than 25% of the population infected with HIV. This article reports on a program that provided HIV services in seven rural clinics in Lesotho. LHWs played an important role in the provision of HIV services that ranged from translation, adherence counseling, voluntary counseling and testing (VCT) for HIV and patient triage, to medication distribution and laboratory specimen processing. Training the LHWs was part of the clinic physicians' responsibilities and thus required no additional funding beyond regular clinic operations. This lent sustainability to the training of the LHWs. This paper describes the recruitment, training, activities, and perceptions of the LHW work between June 2006 and December 2008. LHWs participated successfully in the care of thousands of people with HIV in Lesotho and their experience can serve as a model for other countries facing the disease. PMID- 22304375 TI - Hepatitis: a herbal remedy Germander. PMID- 22304377 TI - Glyphosate-surfactant herbicide products containing glyphosate potassium salt can cause fatal hyperkalemia if ingested in massive amounts. PMID- 22304378 TI - Ibogaine-associated ventricular tachyarrhythmias. PMID- 22304379 TI - A young person's game: immersion and distancing in bar work. AB - Previous research indicates that bar workers report high levels of alcohol consumption, but the bar work experience itself has been little studied as a means to understand health threats associated with this job role. The subjective experience and meaning of bar work was explored in this study by interviewing current and ex-bar workers from a district in an Irish city that had a high density of bars and busy tourism industry. A total of 12 participants took part in focus groups (FGs) and seven in individual interviews. Four themes were identified in a thematic analysis. The central depiction of bar work was of an initial immersion in an intensive lifestyle characterised by heavy drinking, with subsequent distancing from the extremes of the lifestyle. The participants affiliated strongly with the bar work occupational identity, which included alcohol use in group scenarios for drinking during work, after work and on time off. The bar work lifestyle was most intense in the 'superpub' environment, characterised by permissive staff drinking norms and reported stress. Although an important identity, bar work was ultimately a transient role. The findings are considered in relation to research on occupation-specific stress and alcohol use, social identity and developmental needs in young adulthood. PMID- 22304380 TI - Using a low denaturant model to explore the conformational features of translocation-active SecA. AB - The SecA molecular nanomachine in bacteria uses energy from ATP hydrolysis to drive post-translational secretion of preproteins through the SecYEG translocon. Cytosolic SecA exists in a dimeric, "closed" state with relatively low ATPase activity. After binding to the translocon, SecA undergoes major conformational rearrangement, leading to a state that is structurally more "open", has elevated ATPase activity, and is active in translocation. The structural details underlying this conformational change in SecA remain incompletely defined. Most SecA crystal structures report on the cytosolic form; only one structure sheds light on a form of SecA that has engaged the translocon. We have used mild destabilization of SecA to trigger conformational changes that mimic those in translocation-active SecA and thus study its structural changes in a simplified, soluble system. Results from circular dichroism, tryptophan fluorescence, and limited proteolysis demonstrate that the SecA conformational reorganization involves disruption of several domain-domain interfaces, partial unfolding of the second nucleotide binding fold (NBF) II, partial dissociation of the helical scaffold domain (HSD) from NBF I and II, and restructuring of the 30 kDa C terminal region. These changes account for the observed high translocation SecA ATPase activity because they lead to the release of an inhibitory C-terminal segment (called intramolecular regulator of ATPase 1, or IRA1) and of constraints on NBF II (or IRA2) that allow it to stimulate ATPase activity. The observed conformational changes thus position SecA for productive interaction with the SecYEG translocon and for transfer of segments of its passenger protein across the translocon. PMID- 22304382 TI - A structural motif is the recognition site for a new family of bacterial protein O-glycosyltransferases. AB - The Escherichia coli Adhesin Involved in Diffuse Adherence (AIDA-I) is a multifunctional protein that belongs to the family of monomeric autotransporters. This adhesin can be glycosylated by the AIDA-associated heptosyltransferase (Aah). Glycosylation appears to be restricted to the extracellular domain of AIDA I, which comprises imperfect repeats of a 19-amino-acid consensus sequence and is predicted to form a beta-helix. Here, we show that Aah homologues can be found in many Gram-negative bacteria, including Citrobacter rodentium. We demonstrated that an AIDA-like protein is glycosylated in this species by the Aah homologue. We then investigated the substrate recognition mechanism of the E. coli Aah heptosyltransferase. We found that a peptide corresponding to one repeat of the 19-amino-acid consensus is sufficient for recognition and glycosylation by Aah. Mutagenesis studies suggested that, unexpectedly, Aah recognizes a structural motif typical of beta-helices, but not a specific sequence. In agreement with this finding, we observed that the extracellular domain of the Bordetella pertussis pertactin, a beta-helical polypeptide lacking the 19-amino-acid consensus sequence, could be glycosylated by Aah. Overall, our findings suggest that Aah represents the prototype of a new large family of bacterial protein O glycosyltransferases that modify various substrates recognized through a structural motif. PMID- 22304383 TI - Osteoinduction and survival of osteoblasts and bone-marrow stromal cells in 3D biphasic calcium phosphate scaffolds under static and dynamic culture conditions. AB - In many tissue engineering approaches, the basic difference between in vitro and in vivo conditions for cells within three-dimensional (3D) constructs is the nutrition flow dynamics. To achieve comparable results in vitro, bioreactors are advised for improved cell survival, as they are able to provide a controlled flow through the scaffold. We hypothesize that a bioreactor would enhance long-term differentiation conditions of osteogenic cells in 3D scaffolds. To achieve this either primary rat osteoblasts or bone marrow stromal cells (BMSC) were implanted on uniform-sized biphasic calcium phosphate (BCP) scaffolds produced by a 3D printing method. Three types of culture conditions were applied: static culture without osteoinduction (Group A); static culture with osteoinduction (Group B); dynamic culture with osteoinduction (Group C). After 3 and 6 weeks, the scaffolds were analysed by alkaline phosphatase (ALP), dsDNA amount, SEM, fluorescent labelled live-dead assay, and real-time RT-PCR in addition to weekly alamarBlue assays. With osteoinduction, increased ALP values and calcium deposition are observed; however, under static conditions, a significant decrease in the cell number on the biomaterial is observed. Interestingly, the bioreactor system not only reversed the decreased cell numbers but also increased their differentiation potential. We conclude from this study that a continuous flow bioreactor not only preserves the number of osteogenic cells but also keeps their differentiation ability in balance providing a suitable cell-seeded scaffold product for applications in regenerative medicine. PMID- 22304384 TI - Rigid orthogonal bis-TEMPO biradicals with improved solubility for dynamic nuclear polarization. AB - The synthesis and characterization of oxidized bis-thioketal-trispiro dinitroxide biradicals that orient the nitroxides in a rigid, approximately orthogonal geometry are reported. The biradicals show better performance as polarizing agents in dynamic nuclear polarization (DNP) NMR experiments as compared to biradicals lacking the constrained geometry. In addition, the biradicals display improved solubility in aqueous media due to the presence of polar sulfoxides. The results suggest that the orientation of the radicals is not dramatically affected by the oxidation state of the sulfur atoms in the biradical, and we conclude that a biradical polarizing agent containing a mixture of oxidation states can be used for improved solubility without a loss in performance. PMID- 22304385 TI - Design, synthesis, and insecticidal activity of novel pyrazole derivatives containing alpha-hydroxymethyl-N-benzyl carboxamide, alpha-chloromethyl-N-benzyl carboxamide, and 4,5-dihydrooxazole moieties. AB - On the basis of commercial insecticides tebufenpyrad and tolfenpyrad, two series of novel pyrazole-5-carboxamides containing alpha-hydroxymethyl-N-benzyl or alpha chloromethyl-N-benzyl and pyrazoles containing 4,5-dihydrooxazole moieties were designed and synthesized via the key intermediate 2-amino-1-(4-substituted) phenyl ethanol. The structures of target compounds were confirmed by (1)H NMR and elemental analysis or high-resolution mass spectrum (HRMS), and their activities against cotton bollworm (Helicoverpa armigera), diamondback moth (Plutella xylostella), bean aphid (Aphis craccivora), mosquito (Culex pipiens pallens), and spider mite (Tetranychus cinnabarinus) were tested. The results of bioassays indicated that compounds containing alpha-chloromethyl-N-benzyl and compounds containing 4,5-dihydrooxazole showed high insecticidal activity against cotton bollworm. Especially, stomach activities of compounds Ij, Il, and IIe were 60% at 5 mg kg(-1). Moreover, the target compounds exhibited high selectivity between cotton bollworm and diamondback moth, although both of them belong to the order Lepidoptera. Although the activities against diamondback moth were at a low level, some of the target compounds exhibited antifeedant activity. The compounds also had good activities against bean aphid, mosquito, and spider mite. The foliar contact activity of compounds Ic, Id, Ie, and IIf against bean aphid were 95, 95, 100, and 95%, respectively, at 200 mg kg(-1). The miticidal and ovicidal activities of compound IIi against spider mite were both 95% at 200 mg kg(-1). Furthermore, a trivial change at 4-position of pyrazole ring would lead to great changes in properties and activities, which can easily be deduced by comparing the activities of compounds in series I (4-chloro-pyrazole compounds) with corresponding compounds in series II (4-hydro-pyrazole compounds), especially from the miticidal and ovicidal activities of Ii and IIi against spider mite. PMID- 22304386 TI - Ecological and environmental issues faced by a developing Tibet. PMID- 22304387 TI - Disproportionate body composition and perinatal outcome in large-for-gestational age infants to mothers with type 1 diabetes. AB - OBJECTIVE: To determine if disproportionate body composition is a risk factor for perinatal complications in large-for-gestational-age infants born to mothers with type 1 diabetes. DESIGN: Population-based cohort study. SETTING: Data from the Swedish Medical Birth Registry from 1998 to 2007. POPULATION: National cohort of 3517 infants born to mothers with type 1 diabetes. Only singletons with gestational age 32-43 weeks were included. METHODS: Large for gestational age (LGA) was defined as birthweight > 90th centile and appropriate for gestational age (AGA) as birthweight between 10th and 90th centiles. Disproportionate (D) infants were defined as having a ponderal index [PI: calculated as birthweight in grams/(length in cm)(3) > 90th centile] and proportionate (P) as PI <= 90th centile. LGA infants were classified as P-LGA or D-LGA. Odds ratios were calculated for D-LGA and P-LGA infants, with AGA infants as the reference category. Odds ratios were adjusted for mode of delivery, fetal distress and stratified by gestational age. MAIN OUTCOME MEASURES: The primary outcome was a composite of neonatal morbidities, i.e. any of the following diagnoses: Apgar score < 7 at 5 minutes, birth trauma (Erb's palsy or clavicle fracture), respiratory disorder, hyperbilirubinaemia or hypoglycaemia requiring treatment. RESULTS: Composite morbidity was significantly more frequent in LGA as opposed to AGA infants, but there was no difference in risk between P-LGA and D-LGA infants. CONCLUSIONS: High birthweight, irrespective of body proportionality, is a risk factor for neonatal complications in offspring of women with type 1 diabetes. PMID- 22304388 TI - Mobile source and livestock feed contributions to regional ozone formation in Central California. AB - A three-dimensional air quality model with 8 km horizontal resolution was applied to estimate the summertime ozone (O(3)) production from mobile sources and fermented livestock feed in California's San Joaquin Valley (SJV) during years 2000, 2005, 2010, 2015, and 2020. Previous studies have estimated that animal feed emissions of volatile organic compounds (VOCs) have greater O(3) formation potential than mobile-source VOC emissions when averaging across the entire SJV. The higher spatial resolution in the current study shows that the proximity of oxides of nitrogen (NO(x)) and VOC emissions from mobile sources enhances their O(3) formation potential. Livestock feed VOC emissions contributed 3-4 ppb of peak O(3) (8-h average) in Tulare County and 1-2 ppb throughout the remainder of the SJV during the CCOS 2000 July-August episode. In total, livestock feed contributed ~3.5 tons of the ground level peak O(3) (8 h average) in the SJV region, and mobile VOC contributed ~12 tons in this episode. O(3) production from mobile sources is declining over time in response to emissions control plans that call for cleaner fuels and engines with advanced emissions controls. Projecting forward to the year 2020, mobile-source VOC emissions are predicted to produce ~3 tons of the ground level peak O(3)(8-h average) and livestock feed VOC emissions are predicted to contribute ~2.5 tons making these sources nearly equivalent. PMID- 22304389 TI - Lack of mutations of the telomerase RNA component in familial papillary thyroid cancer with short telomeres. AB - BACKGROUND: The occurrence of familial papillary thyroid cancer (FPTC) is well established but no susceptibility genes for this disease have been discovered. Our group has recently demonstrated that patients with FPTC have shorter telomeres, not associated with mutations in telomerase reverse transcriptase, gene than patients with sporadic papillary thyroid cancer (SPTC), healthy subjects (HS), and unaffected family members (UFMs). Several diseases, however, have short telomeres associated with mutations in the telomerase RNA component (TERC) gene or in the shelterin complex (POT1, RAP1, TIN2, TPP1, TRF1, and TRF2) genes. The objective of the present study was to verify whether short telomeres observed in FPTC patients were related to mutations in TERC or shelterin genes. METHODS: Sixty-six patients with FPTC, 46 UFMs, 111 patients with SPTC, and 153 HS were analyzed by polymerase chain reaction followed by denaturing high performance liquid chromatography analysis and direct sequencing for the presence of TERC or shelterin gene mutations. When present, single-nucleotide polymorphisms were tested by chi(2) analysis at the genotypic, allelic, and haplotypic levels. RESULTS: The entire sequence of the TERC gene was analyzed with particular attention to known mutations known to be associated with short telomeres. All samples appeared to be homozygous wild type for A-771G, C-99G, G305A, G322A, C323T, C408G, G450A, T467C, G508A, A514G, G623A, and C727G substitutions and for the 378Delta->3' deletion in the TERC gene. In addition, upon analysis of all samples for shelterin proteins, we observed a significant decrease in POT1 and RAP1 protein expression in the blood of FPTC patients compared with SPTC subjects. However, no mutations or polymorphisms were found when in the coding sequences of both genes. CONCLUSIONS: To our knowledge this is the first study of TERC mutations or alterations in the shelterin complex in relation to FPTC. Shorter telomeres observed in FPTC are not linked to mutations or polymorphisms in TERC, POT1, or RAP1 genes. PMID- 22304390 TI - Ultrasound-guided percutaneous thyroid nodule core biopsy: clinical utility in patients with prior nondiagnostic fine-needle aspirate. AB - BACKGROUND: Five percent to 20% of thyroid nodule fine-needle aspiration (FNA) samples are nondiagnostic. The objective of this study was to determine whether a combination of FNA and core biopsy (CFNACB) would yield a higher proportion of diagnostic readings compared with FNA alone in patients with a history of one or more prior nondiagnostic FNA readings. METHODS: We conducted a retrospective study of 90 core biopsies (CBs) performed in 82 subjects (55 women and 27 men) between 2006 and 2008 in an outpatient clinic. RESULTS: CFNACB yielded a diagnostic reading in 87%. The diagnostic reading yield of the CB component of CFNACB was significantly superior to the concurrent FNA component, with CB yielding a diagnosis in 77% of cases and FNA yielding a diagnosis in 47% (p<0.0001). The combination of CB and FNA had a higher diagnostic reading yield than either alone. In 69 nodules that had only one prior nondiagnostic FNA, CB was diagnostic in 74%, FNA was diagnostic in 52%, CFNACB was diagnostic in 87%, and CB performed significantly better than FNA (p=0.0135). In 21 nodules with two or more prior nondiagnostic FNAs, CFNACB and CB were diagnostic in 86%, FNA was diagnostic in 29%, and CB was significantly better than FNA (p=0.0005). Clinical, ultrasound, or histopathologic follow-up was available for 81% (73/90) of the CFNACB procedures. No subject with a benign CFNACB reading was diagnosed with thyroid malignancy in the follow-up period (range 4-37 months, mean 18 months), although one subject had minimal increase in nodule size and was awaiting repeat sonography at study conclusion. CONCLUSION: Thyroid nodule CFNACB is safe and clinically useful in selected patients when a prior FNA reading is nondiagnostic. CFNACB is superior to either CB or FNA alone. CFNACB should be strongly considered as an alternative to surgery in individuals with two prior nondiagnostic FNAs. PMID- 22304391 TI - Selective release of cytokines, chemokines, and growth factors by minced skin in vitro supports the effectiveness of autologous minced micrografts technique for chronic ulcer repair. AB - A new effective surgical procedure to repair chronic ulcers called minced micrografts technique has been recently reported. The technique consists in spreading a finely minced skin sample upon the wound bed. In this study, we investigate the in vitro release of cytokines (interleukin-6, tumor necrosis factor-alpha, interleukin-1alpha, and granulocyte-colony stimulating factor), chemokines (monocyte chemoattractant protein-1 and growth-related oncogene alpha), and growth factors (platelet-derived growth factor, basic fibroblast growth factor, vascular endothelial growth factor, hepatocyte growth factor, and nerve growth factor) by minced (referred to as the minced sample) vs. not minced (referred to as the whole sample) human skin biopsy samples from the same donor. Factor release in the culture medium at different time points was detected using a multiplexed protein assay. The minced sample, which could behave like the skin fragments used in vivo in the autologous minced micrografts technique, expressed higher levels of tumor necrosis factor-alpha, interleukin-1alpha, platelet derived growth factor, and basic fibroblast growth factor, and lower levels of interleukin-6, monocyte chemoattractant protein-1, growth related oncogene-alpha, and vascular endothelial growth factor compared with the whole sample. In conclusion, mincing of healthy skin may allow appropriate regulation of the inflammatory phase of wound healing and could induce overexpression of some growth factors, which facilitates the proliferative phase of healing. PMID- 22304393 TI - Multiple eruptive pilomatricomas in a 9-year-old boy with glioblastoma. AB - A 9-year-old male presented to our dermatology clinic with a recent history of developing numerous cutaneous pilomatricomas, and was subsequently discovered to have sustained a recurrence of his glioblastoma multiforme. Immunohistochemical staining of a representative pilomatricoma and his original brain tumor revealed upregulation and nuclear localization of beta-catenin, a sign associated with poor prognosis in glioblastoma. We hypothesize that the development of multiple pilomatricomas may have been a hallmark of this patient's tumor recurrence and provide support for a recent report of an association between multiple pilomatricomas and gliomatosis cerebri. PMID- 22304392 TI - Peptidomic analysis of HEK293T cells: effect of the proteasome inhibitor epoxomicin on intracellular peptides. AB - Peptides derived from cytosolic, mitochondrial, and nuclear proteins have been detected in extracts of animal tissues and cell lines. To test whether the proteasome is involved in their formation, HEK293T cells were treated with epoxomicin (0.2 or 2 MUM) for 1 h and quantitative peptidomics analysis was performed. Altogether, 147 unique peptides were identified by mass spectrometry sequence analysis. Epoxomicin treatment decreased the levels of the majority of intracellular peptides, consistent with inhibition of the proteasome beta-2 and beta-5 subunits. Treatment with the higher concentration of epoxomicin elevated the levels of some peptides. Most of the elevated peptides resulted from cleavages at acidic residues, suggesting that epoxomicin increased the processing of proteins through the beta-1 subunit. Interestingly, some of the peptides that were elevated by the epoxomicin treatment had hydrophobic residues in P1 cleavage sites. Taken together, these findings suggest that, while the proteasome is the major source of intracellular peptides, other peptide-generating mechanisms exist. Because intracellular peptides are likely to perform intracellular functions, studies using proteasome inhibitors need to be interpreted with caution, as it is possible that the effects of these inhibitors are due to a change in the peptide levels rather than inhibition of protein degradation. PMID- 22304394 TI - An innovative screen-and-advice model for psychopathology and psychosocial problems among urban pregnant women: an exploratory study. AB - BACKGROUND: Increased adverse pregnancy outcomes related to psychiatric and psychosocial problems can be observed for urban areas when compared to national averages. We developed a personal digital assistant (PDA)-based self-report screening model that produces tailored intervention advices. After having adapted the model to local care pathways, we tested the reliability, validity and feasibility of the model in routine antenatal care. METHODS: Observational study among pregnant women in a Dutch urban area included women with a booking visit. Women answered questions posed by the PDA-tool while waiting for their appointment. If the tool suggested specific interventions (screen result), this was discussed during booking visit. A randomly selected subsample of participants completed the questionnaire again at a subsequent pregnancy check (retest). After the study was conducted, prenatal caregivers and assistants were interviewed for feasibility judgments. Psychometric and diagnostic performance of this approach was established. RESULTS: Response rate among invited pregnant women was 94% on weighted average (n=621). Internal reliability ranged 0.88-0.90, test-retest reliability ranged 0.64-1.00. Positive predictive value was 86% and negative predictive value was 97%. No interpractice psychometrical differences were observed. Migrant women more often received an intervention advice than native women (p<0.001). The approach was well accepted among prenatal caregivers for its time efficiency and patient-friendliness. CONCLUSION: Psychometric properties of our screen-and-advice tool were favorable under routine conditions, and the feasibility of this integral approach appeared good. The technical flexibility renders the model suitable for broader application. Local care pathways can easily be incorporated. We suggest implementation of this model in prenatal care in urbanized settings in order to make tailored mental healthcare broadly available. PMID- 22304395 TI - Perceived control and maternal satisfaction with childbirth: a measure development study. AB - The purpose of this study was to develop and validate two instruments: one to assess patient perceptions of control of the childbirth environment and the other, global satisfaction with the childbirth experience. Participants were 187 women recruited from obstetric clinics, breast-feeding support groups and online who had given birth in the past 4 months. Scale development involved item construction, exploratory factor analysis (EFA) of the Perceived Control in Childbirth Scale (PCCh), confirmatory factor analysis (CFA) of the Satisfaction with Childbirth Scale (SWCh), reliability analysis and construct validity analyses. EFA identified a single factor underlying a set of items reflecting the patient's belief that her actions influenced the birth environment (i.e. perceived control). CFAs supported a single-factor model reflecting the degree to which the birth experience met the patient's ideal (i.e. satisfaction). Perceived control was associated with childbirth self-efficacy. Childbirth satisfaction was associated with both affective reactions to birth and childbirth-related posttraumatic stress disorder (PTSD) symptoms. Results support the validity and reliability of two new scales that assess perceived control of the birth environment and global satisfaction with childbirth. PMID- 22304397 TI - Hypervolemic infusion of Lumbricus terrestris erythrocruorin purified by tangential-flow filtration. AB - BACKGROUND: The hemoglobin of the earthworm Lumbricus terrestris (also known as erythrocruorin, or LtEc) is a naturally occurring high-molecular-weight protein assembly (3.6 MDa) that is extremely stable, resistant to oxidation, and transports oxygen similarly to human whole blood. Therefore, LtEc may serve as an alternative to donated human red blood cells. However, a suitable purification process must be developed to produce highly pure LtEc on a large scale that can be evaluated in an animal model to determine the safety and efficacy of LtEc. STUDY DESIGN AND METHODS: We used tangential-flow filtration (TFF), an easily scalable and affordable technique, to produce highly pure LtEc from earthworms. The purity, yield, methemoglobin level, viscosity, colloid osmotic pressure, O(2) binding equilibria, and ligand-binding kinetics of the purified LtEc were measured in vitro. The purified LtEc product was then evaluated in hamsters using a hypervolemic infusion model to establish its basic biocompatibility and detect any changes in microcirculatory and systemic variables. RESULTS: TFF was able to produce LtEc with high purity and yield (5-10 g/1000 worms). The purified LtEc product did not elicit hypertension or vasoconstriction when infused into hamsters. CONCLUSION: LtEc may be easily purified and safely transfused into hamsters in small amounts (0.5-1.5 g/dL final concentration in blood) without any noticeable side effects. Therefore, LtEc may serve as a very promising oxygen carrier for use in transfusion medicine. PMID- 22304398 TI - Electrostatic protein immobilization using charged polyacrylamide gels and cationic detergent microfluidic Western blotting. AB - We report a novel protein immobilization matrix for fully integrated microfluidic Western blotting (WB). The electrostatic immobilization gel (EIG) enables immobilization of all proteins sized using cetyl trimethylammonium bromide polyacrylamide gel electrophoresis (CTAB-PAGE), for subsequent electrophoretic probing with detection affinity reagents (e.g., labeled antibodies). The "pan analyte" capture strategy introduced here uses polyacrylamide gel grafted with concentrated point charges (zwitterionic macromolecules), in contrast to existing microfluidic WB strategies that rely on a sandwich immunoassay format for analyte immobilization and detection. Sandwich approaches limit analyte immobilization to capture of only a priori known targets. A charge interaction mechanism study supports the hypothesis that electrostatic interaction plays a major role in analyte immobilization on the EIG. We note that protein capture efficiency depends on both the concentration of copolymerized charges and ionic strength of the gel buffer. We demonstrate pan-analyte immobilization of sized CTAB-laden model proteins (protein G, ovalbumin, bovine serum albumin, beta-galactosidase, lactoferrin) on the EIG with initial capture efficiencies ranging from 21 to 100%. Target proteins fixed on the EIG (protein G, lactoferrin) are detected using antibody probes with signal-to-noise ratios of 34 to 275. The approach advances protein immunoblotting performance through 200* reduction on sample consumption, 12* reduction in assay duration, and automated assay operation, compared to slab-gel WB. Using the microfluidic WB assay, assessment of lactoferrin in human tear fluid is demonstrated with a goal of advancing toward nonbiopsy-based diagnosis of Sjogren's Syndrome, an autoimmune disease. PMID- 22304399 TI - Functional outcomes in African-Americans after robot-assisted radical prostatectomy. AB - BACKGROUND AND PURPOSE: Previous studies have demonstrated differences in surgical outcomes after radical prostatectomy based on ethnicity. We compared sexual and urinary outcomes in African-American (AA) patients 6 and 12 months after robot-assisted radical prostatectomy (RARP) with those of non-AA patients. PATIENTS AND METHODS: We reviewed our RARP database at our institution for patients with at least 12 months of follow-up. Erectile function was defined using the University of California, Los Angeles Prostate Cancer Index as erections "firm enough for masturbation and foreplay" or "firm enough for intercourse," while urinary continence was defined as being "pad free." Only patients who were potent and pad free preoperatively were included in the analysis. Multivariate logistic regression was used to compare postoperative potency and urinary pad-free status between AA and non-AA patients while controlling for pertinent demographic, clinical, and pathologic variables. RESULTS: In the urinary continence analysis, 140 AA patients and 576 non-AA patients were included, compared with 105 AAs and 500 non-AA patients who were included in the analysis of sexual function. At 12 months postoperatively, a smaller proportion of AA patients were potent compared with non-AA patients (60% vs 76.4%, P=0.001). Similarly, we found a lower incidence of pad-free status for AA patients at 12 months postoperatively (55.7% vs 69.8%, P=0.039). Similar functional results were found at 6 months postoperatively for both analysis groups. CONCLUSION: AA men appear to have worse urinary and sexual outcomes at 12 months after RARP compared with non-AA patients. At 6 months, there is no statistically significant difference. Further, longer-term studies are needed to validate these results. PMID- 22304400 TI - Fluidity modulation of phospholipid bilayers by electrolyte ions: insights from fluorescence microscopy and microslit electrokinetic experiments. AB - Fluidity and charging of supported bilayer lipid membranes (sBLMs) prepared from 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) were studied by fluorescence recovery after photobleaching (FRAP) and microslit electrokinetic measurements at varying pH and ionic composition of the electrolyte. Measurements in neutral electrolytes (KCl, NaCl) revealed a strong correlation between the membrane fluidity and the membrane charging due to unsymmetrical water ion adsorption (OH( ) ? H(3)O(+)). The membrane fluidity significantly decreased below the isoelectric point of 3.9, suggesting a phase transition in the bilayer. The interactions of both chaotropic anions and strongly kosmotropic cations with the zwitterionic lipids were found to be related with nearly unhindered lipid mobility in the acidic pH range. While for the chaotropic anions the observed effect correlates with the increased negative net charge at low pH, no correlation was found between the changes in the membrane fluidity and charge in the presence of kosmotropic cations. We discuss the observed phenomena with respect to the interaction of the electrolyte ions with the lipid headgroup and the influence of this process on the headgroup orientation and hydration as well as on the lipid packaging. PMID- 22304401 TI - The online romance scam: a serious cybercrime. AB - The Online Romance Scam is a relatively new form of fraud that became apparent in about 2008. In this crime, criminals pretend to initiate a relationship through online dating sites then defraud their victims of large sums of money. This paper presents some descriptive statistics about knowledge and victimization of the online dating romance scam in Great Britain. Our study found that despite its newness, an estimated 230,000 British citizens may have fallen victim to this crime. We conclude that there needs to be some rethinking about providing avenues for victims to report the crime or at least making them more comfortable when doing so. PMID- 22304402 TI - Predicting undergraduates' self-reported engagement in traditional and cyberbullying from attitudes. AB - Studies indicate that attitudes predict traditional forms of bullying. Fewer studies have tested this for cyberbullying, in which the harassment is delivered via electronic communication technology. The current study represents the first direct comparison of attitudes toward the two forms of bullying among undergraduates (N=405). It also tested the hypothesis that engagement in traditional and cyberbullying could be predicted from attitudes toward bullying behavior, bullies, and victims. Results indicated that participants held least favorable attitudes toward physical bullying/bullies, more accepting attitudes toward verbal bullying/bullies, and attitudes toward forms of cyberbullying/bullies somewhere in between. Significant sex differences were also obtained; women expressed significantly less accepting attitudes toward bullying behavior and perpetrators, and more accepting attitudes toward victims, across all subtypes of bullying. The hypothesis that attitudes predict bullying behavior received some support. Some similarities and differences emerged for cyber and traditional forms. The implications for future research, theory building, and interventions are discussed. PMID- 22304403 TI - Communicating creativity on YouTube: what and for whom? AB - This article addresses nonprofessional users' expressions of everyday creativity on YouTube, adopting the idea that making entails connecting on different levels. By combining different materials and ideas into a video and sharing it within the social context of the platform, uploaders can connect with its enormous audience. In our first study, we explore patterns in the elements that are used when creating a video. We also question whether these pattern combinations are aimed at different types of viewers. Our results show that videos with self-made content that display various skills are mainly targeted at viewers situated close to the uploader (e.g., family, friends). However, videos that incorporate instances of popular culture, either as a whole (e.g., a pop concert recording) or in part (e.g., remixed with other content), are directed at a much broader audience. In our second study, we question whether these self-made videos convey a message about uploaders' personality traits commonly linked to creative behavior. We found that independent observers are able to accurately predict the uploaders' actual openness to experience, a trait marked as the substrate of creativity. Next, we discuss our results in light of a pessimistic view of today's democratized culture. We show that uploaders appear to have a tacit knowledge of what kind of videos are interesting for what type of viewers. We conclude that, despite the lowered barriers to the production and dissemination of video, YouTube viewers are still able to identify variations in the personality trait most commonly associated to creativity. PMID- 22304404 TI - Cyber incivility @ work: the new age of interpersonal deviance. AB - The current study was designed to extend the interpersonal deviance literature into the online domain by examining the incidence and impact of supervisor cyber incivility and neuroticism on employee outcomes at work. Conservation of Resources (COR) theory was used as the guiding framework because cyber incivility is thought to deplete energetic resources in much the same way that other stressors do, ultimately leading to negative outcomes like burnout. Results indicate that supervisor cyber incivility is positively related to burnout, absenteeism, and turnover intentions. Support was also found for the role of neuroticism as a moderator of the relationship between supervisor cyber incivility and outcomes. In general, the relations between cyber incivility and outcomes were stronger for those individuals reporting higher levels of neuroticism. Results are discussed in terms of COR theory, and possible mechanisms for the role of neuroticism in the stressor-strain relationship are discussed. The current study highlights the importance of understanding workplace online behavior and its impact on employee health and organizational well-being. Future research directions examining online interpersonal deviance are suggested. PMID- 22304405 TI - Nonionic homopolymeric amphipols: application to membrane protein folding, cell free synthesis, and solution nuclear magnetic resonance. AB - Nonionic amphipols (NAPols) synthesized by homotelomerization of an amphiphatic monomer are able to keep membrane proteins (MPs) stable and functional in the absence of detergent. Some of their biochemical and biophysical properties and applications have been examined, with particular attention being paid to their complementarity with the classical polyacrylate-based amphipol A8-35. Bacteriorhodopsin (BR) from Halobacterium salinarum and the cytochrome b(6)f complex from Chlamydomonas reinhardtii were found to be in their native state and highly stable following complexation with NAPols. NAPol-trapped BR was shown to undergo its complete photocycle. Because of the pH insensitivity of NAPols, solution nuclear magnetic resonance (NMR) two-dimensional (1)H-(15)N heteronuclear single-quantum coherence spectra of NAPol-trapped outer MP X from Escherichia coli (OmpX) could be recorded at pH 6.8. They present a resolution similar to that of the spectra of OmpX/A8-35 complexes recorded at pH 8.0 and give access to signals from solvent-exposed rapidy exchanging amide protons. Like A8-35, NAPols can be used to fold MPs to their native state as demonstrated here with BR and with the ghrelin G protein-coupled receptor GHS-R1a, thus extending the range of accessible folding conditions. Following NAPol-assisted folding, GHS R1a bound four of its specific ligands, recruited arrestin-2, and activated binding of GTPgammaS by the G(alphaq) protein. Finally, cell-free synthesis of MPs, which is inhibited by A8-35 and sulfonated amphipols, was found to be very efficient in the presence of NAPols. These results open broad new perspectives on the use of amphipols for MP studies. PMID- 22304406 TI - Little pitchers use their big ears: preschoolers solve problems by listening to others ask questions. AB - Children ask questions and learn from the responses they receive; however, little is known about how children learn from listening to others ask questions. Five experiments examined preschoolers' (N = 179) ability to solve simple problems using information gathered from listening to question-and-answer exchanges between 2 parties present in the same room. Overall, the ability to efficiently use information gathered from overheard exchanges improved between ages 3 and 5. Critically, however, across ages children solved the majority of problems correctly, suggesting preschoolers are capable of learning from others' questions. Moreover, children learned from others' questions without explicit instruction and when engaged in another activity. Implications for the development of problem-solving skills are discussed. PMID- 22304408 TI - Leukemia inhibitory factor: a paracrine mediator of bone metabolism. AB - Leukemia inhibitory factor (LIF) is a soluble interleukin-6 family cytokine that regulates a number of physiologic functions, including normal skeletal remodeling. LIF signals through the cytokine co-receptor glycoprotein-130 in complex with its cytokine-specific receptor [LIF receptor (LIFR)] to activate signaling cascades in cells of the skeletal system, including stromal cells, chondrocytes, osteoblasts, osteocytes, adipocytes, and synovial fibroblasts. LIF action on skeletal cells is cell-type specific, and frequently dependent on the state of cell differentiation. This review describes the expression patterns of LIF and LIFR in bone, their regulation by physiological and inflammatory agents, as well as cell-specific influences of LIF on osteoblast, osteoclast, chondrocyte, and adipocyte differentiation. The actions of LIF in normal skeletal growth and maintenance, in pathological states (e.g. autocrine tumor cell signaling and growth in bone) and inflammatory conditions (e.g. arthritis) will be discussed, as well as the signaling pathways activated by LIF and their importance in bone formation and resorption. PMID- 22304409 TI - Unconscious response priming by shape depends on geniculostriate visual projection. AB - It has been suggested that unconscious visual processing of some stimulus features might occur without the contribution of early visual cortex (V1/V2). In the present study, the causal role of V1/V2 in unconscious processing of simple shapes in intact human brain was studied by applying transcranial magnetic stimulation (TMS) on early visual cortex or lateral occipital cortex (LO) while observers performed a metacontrast-masked response priming task with arrow figures as visual stimuli. Magnetic stimulation of V1/V2 impaired masked priming 30-90 ms after the onset of the prime. Stimulation of LO reduced the magnitude of masked priming at 90-120 ms, but this effect occurred only in the early parts of the priming experiment. A control task measuring the visibility of masked primes indicated that the orientation of masked primes could not be consciously discriminated and that TMS did not influence the conscious visibility of the primes indirectly by reducing the effectiveness of the mask in the critical time windows. We conclude that feedforward sweep of processing from V1/V2 (30-90 ms) to LO (90 ms and above) is necessary for unconscious priming of shape, whereas conscious perception requires also the contribution of recurrent (feedback) processing. PMID- 22304410 TI - Overexpression of mouse TTF-2 gene causes cleft palate. AB - In humans, mutations of the gene encoding for thyroid transcription factor-2 (TTF 2 or FOXE1) result in Bamforth syndrome. Bamforth syndrome is characterized by agenesis, cleft palate, spiky hair and choanal atresia. TTF-2 null mice (TTF-2(-/ ) ) also exhibit cleft palate, suggesting its involvement in the palatogenesis. However, the molecular pathology and genetic regulation by TTF2 remain largely unknown. In the present study, the recombinant expression vector pBROAD3-TTF-2 containing the promoter of the mouse ROSA26 gene was created to form the structural gene of mouse TTF-2 and was microinjected into the male pronuclei of fertilized ova. Sequence analysis confirmed that the TTF-2 transgenic mouse model was established successfully. The transgenic mice displayed a phenotype of cleft palate. In addition, we found that TTF-2 was highly expressed in the medial edge epithelium (MEE) from the embryonic day 12.5 (E12.5) to E14.5 in TTF-2 transgenic mice. These observations suggest that overexpression of TTF-2 during palatogenesis may contribute to formation of cleft palate. PMID- 22304411 TI - Molecular dynamics simulation of the unfolding of individual bacteriorhodopsin helices in sodium dodecyl sulfate micelles. AB - We report molecular dynamics simulations of the trends in the changes in secondary structure of the seven individual helices of bacteriorhodopsin when inserted into sodium dodecyl sulfate (SDS) micelles, and their dependence on the amino acid sequence. The results indicate that the partitioning of the helices in the micelles and their stability are dependent on the hydrophobicity of the transmembrane segments. Helices A, B, and E are stable and retain their initial secondary structure throughout the 100 ns simulation time. In contrast, helices C, D, F, and G show structural perturbations within the first 10 ns. The instabilities are localized near charged residues within the transmembrane segments. The overall structural instability of the helix is correlated with its partitioning to the surface of the micelle and its interaction with polar groups there. The in silico experiments were performed to complement the in vitro experiments that examined the partial denaturation of bacteriorhodopsin in SDS described in the preceding article (DOI 10.1021/bi201769z ). The simulations are consistent with the trends revealed by the experimental results but strongly underestimate the extent of helix to extended coil transformation. The reason may be either that the sampling time was not sufficiently long or, more interestingly, that interhelix residue interactions play a role in the unfolding of the helices. PMID- 22304412 TI - The impact of maternal body mass index on the phenotype of pre-eclampsia: a prospective cohort study. AB - OBJECTIVE: We hypothesised that among nulliparous women with pre-eclampsia, overweight or obese women would have a different phenotype of pre-eclampsia compared with normal weight women with pre-eclampsia. Specifically, they are more likely to develop term pre-eclampsia and less likely to have indicators of impaired placental perfusion, e.g. abnormal uterine artery Doppler or a small-for gestational-age (SGA) infant. DESIGN: Prospective, multicentre, cohort SCOPE study (n = 3170). SETTING: New Zealand and Australia. POPULATION: Nulliparous women who developed pre-eclampsia. METHODS: Participants were interviewed at 14 16 weeks of gestation, uterine artery Doppler studies were performed at 19-21 weeks and pregnancy outcome was tracked prospectively. MAIN OUTCOME MEASURES: Rates of abnormal uterine artery Doppler indices, term/preterm birth and SGA infants were compared between normal, overweight and obese women with pre eclampsia. Multivariable analysis was performed to examine the association between body mass index (BMI) and term pre-eclampsia. RESULTS: Of 178 women with pre-eclampsia, one underweight woman was excluded and 66 (37%) were normal weight, 52 (29%) were overweight and 59 (34%) were obese. Pre-eclampsia developed preterm in 26% of women and at term in 74% of women. There were no differences in the rates of term/preterm pre-eclampsia, abnormal uterine artery Doppler indices or SGA infants between BMI groups (P > 0.10). No independent association between BMI and term pre-eclampsia was found (P = 0.56). CONCLUSIONS: Among women with pre-eclampsia, those who are overweight or obese in early pregnancy are not more likely to have term pre-eclampsia compared with women with a normal BMI. Overweight and obese women require vigilant surveillance for the development of preterm as well as term pre-eclampsia. PMID- 22304413 TI - Exploitation of wild Chinese herbs leads to environmental degradation and possible loss of the resource. PMID- 22304414 TI - Evaluating the potential for secondary mass savings in vehicle lightweighting. AB - Secondary mass savings are mass reductions that may be achieved in supporting (load-bearing) vehicle parts when the gross vehicle mass (GVM) is reduced. Mass decompounding is the process by which it is possible to identify further reductions when secondary mass savings result in further reduction of GVM. Maximizing secondary mass savings (SMS) is a key tool for maximizing vehicle fuel economy. In today's industry, the most complex parts, which require significant design detail (and cost), are designed first and frozen while the rest of the development process progresses. This paper presents a tool for estimating SMS potential early in the design process and shows how use of the tool to set SMS targets early, before subsystems become locked in, maximizes mass savings. The potential for SMS in current passenger vehicles is estimated with an empirical model using engineering analysis of vehicle components to determine mass dependency. Identified mass-dependent components are grouped into subsystems, and linear regression is performed on subsystem mass as a function of GVM. A Monte Carlo simulation is performed to determine the mean and 5th and 95th percentiles for the SMS potential per kilogram of primary mass saved. The model projects that the mean theoretical secondary mass savings potential is 0.95 kg for every 1 kg of primary mass saved, with the 5th percentile at 0.77 kg/kg when all components are available for redesign. The model was used to explore an alternative scenario where realistic manufacturing and design limitations were implemented. In this case study, four key subsystems (of 13 total) were locked-in and this reduced the SMS potential to a mean of 0.12 kg/kg with a 5th percentile of 0.1 kg/kg. Clearly, to maximize the impact of mass reduction, targets need to be established before subsystems become locked in. PMID- 22304415 TI - Indirect comparisons of adverse events and dropout rates in early Parkinson's disease trials of pramipexole, ropinirole, and rasagiline. AB - The comparative safety profiles of monotherapeutic treatments for Parkinson's disease (PD) can provide valuable therapeutic information. The objective of this study was to perform an indirect comparison of Adverse Events (AEs) and Dropout Rates (DRs) among clinical trials of pramipexole, ropinirole, and rasagiline. Outcomes analyzed included DRs, total AEs, and AE categories: Cognitive (CG), Gastrointestinal (GI), and Sleep/Fatigue (SF). The odds-ratio (OR) and Credible Interval (CrI) of outcomes between products using placebo as common comparator was calculated using indirect meta-analytical methods. AEs incidences for subjects receiving rasagiline were not significantly different from placebo, whereas DRs were significantly lower than for placebo (OR = 0.55; 95% CrI = 0.34 0.88). Patients receiving pramipexole or ropinirole had higher incidence of all AEs and DRs than patients taking rasagiline, except for the nonsignificant incidence of CG for ropinirole vs. rasagiline (1.76; 0.69-4.70). The incidence of GI (2.11; 1.13-4.06) and SF (2.75; 1.42-5.47) was significantly higher for ropinirole than for pramipexole, whereas the incidence of CG was significantly lower for ropinirole than for pramipexole (0.22; 0.07-0.69). Findings suggest that subjects with early PD treated with rasagiline have fewer AEs and DRs than those treated with pramipexole or ropinirole. GI and SF AEs were highest for subjects treated with ropinirole, while individuals treated with pramipexole exhibited the highest incidence of cognitive AEs. PMID- 22304417 TI - Core-needle biopsy is more useful than repeat fine-needle aspiration in thyroid nodules read as nondiagnostic or atypia of undetermined significance by the Bethesda system for reporting thyroid cytopathology. AB - BACKGROUND: Thyroid nodules with fine-needle aspiration (FNA) readings of nondiagnostic or atypia of undetermined significance (AUS), also referred to as follicular lesion of undetermined significance (FLUS) are problematic for their optimal management. The usefulness of performing a core-needle biopsy (CNB) to clarify whether these nodules are benign or malignant has not been established. The purpose of the present study was to determine whether CNB provides better diagnostic information than repeat FNA (rFNA) in thyroid nodules having nondiagnostic or AUS/FLUS readings. MATERIALS AND METHODS: The Bethesda System for Reporting Thyroid Cytopathology was used for FNA readings and for CNB readings. The study included 225 thyroid nodules from 220 consecutive patients who previously had nondiagnostic (Group N-DIAG, n=64) or AUS/FLUS (Group AF, n=161) FNA readings. All patients simultaneously underwent rFNA and CNB of each nodule. The nondiagnostic and AUS/FLUS readings by rFNA and by CNB were compared. The diagnostic sensitivities of rFNA and CNB for malignancy in thyroid nodules were also assessed. Statistical analysis was performed using a McNemar's test. RESULTS: In N-DIAG Group, the nondiagnostic readings for the CNBs were lower than that those for rFNAs (1.6% vs. 28.1%, p<0.001). In the AF Group, the AUS/FLUS readings for the CNBs were lower than those for the rFNAs (23.6% vs. 39.8%, p<0.001). The inconclusive diagnoses (nondiagnostic or AUS/FLUS) for the CNBs were lower than those for the rFNAs in Group N-DIAG (12.5% vs. 45.3%, p<0.001) and Group AF (26.7% vs. 49.1%, p<0.001). The sensitivity of CNB for thyroid malignancy was higher than that of rFNA in Group N-DIAG (100% vs. 71.4%, p=0.125) and Group AF (78.5% vs. 55.4%, p<0.001). CONCLUSION: After patients have had one FNA of a thyroid nodule yielding inconclusive diagnostic results (nondiagnostic or AUS/FLUS), CNB is more useful than rFNA for reducing the frequency of inconclusive diagnostic results. CNB will improve the diagnostic performance for malignancy more than rFNA in thyroid nodules that on the first FNA had nondiagnostic or AUS/FLUS readings. PMID- 22304416 TI - N-linked glycan structures and their expressions change in the blood sera of ovarian cancer patients. AB - Glycosylated proteins play important roles in a broad spectrum of biochemical and biological processes, and prior reports have suggested that changes in protein glycosylation occur during cancer initiation and progression. Ovarian cancer (OC) is a fatal malignancy, most commonly diagnosed after the development of metastases. Therefore, early detection of OC is key to improving survival. To this end, specific changes of the serum glycome have been proposed as possible biomarkers for different types of cancers. In this study, we extend this concept to OC. To characterize differences in total N-glycan levels, serum samples provided by 20 healthy control women were compared to those acquired from patients diagnosed with late-stage recurrent OC who were enrolled in an experimental treatment trial prior to receiving therapy (N=19) and one month later, prior to the second treatment cycle (N=11). Additionally, analyses of the N-glycans associated with IgG and characterization of the relative abundance levels of core vs outer-arm fucosylation were also performed. The N-linked glycomic profiles revealed increased abundances of tri- and tetra-branched structures with varying degrees of sialylation and fucosylation and an apparent decrease in the levels of "bisecting" glycans in OC samples compared to controls. Increased levels of a-galactosylation structures were observed on N-linked glycans derived from IgG, which were independent of the presence of fucose residues. Elevated levels of outer-arm fucosylation were also identified in the OC samples. These results allowed the control samples to be distinguished from the baseline ovarian cancer patients prior to receiving the experimental treatment. In some cases, the pre-treatment samples could be distinguished from the post-experimental treatment samples, as many of those patients showed a further progression of the disease. PMID- 22304418 TI - Protein G, protein A and protein A-derived peptides inhibit the agitation induced aggregation of IgG. AB - Controlling and preventing aggregation is critical to the development of safe and effective antibody drug products. The studies presented here test the hypothesis that protein A and protein G inhibit the agitation-induced aggregation of IgG. The hypothesis is motivated by the enhanced conformational stability of proteins upon ligand binding and the specific binding affinity of protein A and protein G to the Fc region of IgG. The aggregation of mixed human IgG from pooled human plasma was induced by agitation alone or in the presence of (i) protein A, (ii) protein G or (iii) a library of 24 peptides derived from the IgG-binding domain of protein A. Aggregation was assessed by UV spectroscopy, SDS-PAGE, high performance size-exclusion chromatography (HP-SEC), dynamic light scattering (DLS) and fluorescence spectroscopy. Additional information on IgG-ligand interactions was obtained using differential scanning fluorimetry (DSF) and competitive binding studies. The results demonstrate that protein A provides near complete inhibition of agitation-induced aggregation, while protein G and two peptides from the peptide library show partial inhibition. The findings indicate that the IgG protein A-binding site is involved in the agitation-induced aggregation of IgG, and suggest a dominant role of colloidal interactions. PMID- 22304419 TI - Diversity of flavin-binding monooxygenase genes (almA) in marine bacteria capable of degradation long-chain alkanes. AB - Many bacteria have been reported as degraders of long-chain (LC) n-alkanes, but the mechanism is poorly understood. Flavin-binding monooxygenase (AlmA) was recently found to be involved in LC-alkane degradation in bacteria of the Acinetobacter and Alcanivorax genera. However, the diversity of this gene and the role it plays in other bacteria remains unclear. In this study, we surveyed the diversity of almA in marine bacteria and in bacteria found in oil-enrichment communities. To identify the presence of this gene, a pair of degenerate PCR primers were was designed based on conserved motifs of the almA gene sequences in public databases. Using this approach, we identified diverse almA genes in the hydrocarbon-degrading bacteria and in bacterial communities from the surface seawater of the Xiamen coastal area, the South China Sea, the Indian Ocean, and the Atlantic Ocean. As a result, almA was positively detected in 35 isolates belonging to four genera, and a total of 39 different almA sequences were obtained. Five isolates were confirmed to harbor two to three almA genes. From the Xiamen coastal area and the Atlantic Ocean oil-enrichment communities, a total of 60 different almA sequences were obtained. These sequences mainly formed two clusters in the phylogenetic tree, named Class I and Class II, and these shared 45-56% identity at the amino acid level. Class I contained 11 sequences from bacteria represented by the Salinisphaera and Parvibaculum genera. Class II was larger and more diverse, and it was composed of 88 sequences from Proteobacteria, Gram-negative bacteria, and the enriched bacterial communities. These communities were represented by the Alcanivorax and Marinobacter genera, which are the two most popular genera hosting the almA gene. AlmA was also detected across a wide geographical range, as determined by the origin of the bacterial host. Our results demonstrate the diversity of almA and confirm its high rate of occurrence in hydrocarbon-degrading bacteria, indicating that this gene plays an important role in the degradation of LC alkanes in marine environments. PMID- 22304420 TI - Severe dyshidrotic eczema after intravenous immunoglobulin therapy for Kawasaki syndrome. AB - Dyshidrotic eczema is one of the rare cutaneous adverse effects of intravenous immunoglobulin therapy, usually seen in adults. We herein report the first pediatric case of severe dyshidrotic eczema occurring after intravenous immunoglobulin therapy for Kawasaki syndrome. PMID- 22304421 TI - Recognition of facial expressions of emotion in adults with Down syndrome. AB - Research on facial expressions in individuals with Down syndrome (DS) has been conducted using photographs. Our goal was to examine the effect of motion on perception of emotional expressions. Adults with DS, adults with typical development matched for chronological age (CA), and children with typical development matched for developmental age (DA) viewed photographs and video clips of facial expressions of: happy, sad, mad, and scared. The odds of accurate identification of facial expressions were 2.7 times greater for video clips compared with photographs. The odds of accurate identification of expressions of mad and scared were greater for video clips compared with photographs. The odds of accurate identification of expressions of mad and sad were greater for adults but did not differ between adults with DS and children. Adults with DS demonstrated the lowest accuracy for recognition of scared. These results support the importance of motion cues in evaluating the social skills of individuals with DS. PMID- 22304422 TI - The clinical relevance of persistent recombinant immunoblot assay-indeterminate reactions: insights into the natural history of hepatitis C virus infection and implications for donor counseling. AB - BACKGROUND: Recombinant immunoblot assay (RIBA) is used to determine the specificity of antibody to hepatitis C virus (anti-HCV). The RIBA result is recorded as positive, negative, or indeterminate. The interpretation and significance of RIBA-indeterminate reactions are unclear. We addressed the clinical relevance of these reactions in the context of the natural history of HCV infection in a prospectively followed cohort of anti-HCV-positive blood donors. STUDY DESIGN AND METHODS: Donor demographics, exposure history, and humoral and cell-mediated immunity (CMI) were compared in 15 RIBA-indeterminate subjects, nine chronic HCV carriers, and eight spontaneously recovered subjects. Serum samples were tested for anti-HCV by a quantitative, liquid luciferase immunoprecipitation system (LIPS). CMI was assessed by interferon-gamma enzyme linked immunosorbent spot assay. RESULTS: In the LIPS assay, the sum of antibody responses to six HCV antigens showed significant (p < 0.001) stepwise diminution progressing from chronic carriers to spontaneously recovered to RIBA indeterminate subjects. CMI responses in RIBA-indeterminate subjects were similar to spontaneously recovered subjects and greater than chronic carriers and controls (p < 0.008). A parenteral risk factor was identified in only 13% of RIBA indeterminate subjects compared to 89% of chronic carriers and 87% of spontaneously recovered subjects. RIBA-indeterminate donors were older than the other groups. CONCLUSION: The CMI and LIPS results suggest that persistent RIBA indeterminate reactions represent waning anti-HCV responses in persons who have recovered from a remote HCV infection. In such cases, detectable antibody may ultimately disappear leaving no residual serologic evidence of prior HCV infection, as reported in a minority of long-term HCV-recovered subjects. PMID- 22304423 TI - Evanescent wave cavity ringdown spectroscopy: a platform for the study of supported lipid bilayers. AB - Evanescent wave cavity ringdown spectroscopy (EW-CRDS) is advocated as an approach for monitoring the formation of supported lipid bilayers (SLBs) on quartz substrates in situ and for the quantitative study of fast molecular adsorption kinetics at the resulting modified biomimetic surface. This approach is illustrated using SLBs of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). Complementary atomic force microscopy (AFM) and quartz crystal microbalance with dissipation (QCM-D) measurements confirm the formation of bilayers on quartz. The subsequent interaction of the porphyrin, 5,10,15,20-tetraphenyl-21H,23H-porphine p,p',p'',p'''-tetrasulfonic acid tetrasodium hydrate (TPPS) with the cationic bilayer-modified silica surface has been studied using EW-CRDS combined with an impinging-jet to deliver analyte to the surface in a well-defined manner. The adsorption of TPPS to the bilayer was kinetically controlled and the adsorption rate constant was found to be 1.7 (+/-0.6) * 10(-4) cm s(-1) from finite element modeling of the jet hydrodynamics and associated convective-diffusion equation, coupled to a first-order surface process describing adsorption. These proof-of concept studies provide a platform for the investigation of molecular processes at biomembranes using EW-CRDS for chemical species showing optical absorbance in the visible and ultraviolet range. PMID- 22304424 TI - Ureteroscopic management with laser lithotripsy of renal pelvic stones. AB - BACKGROUND AND PURPOSE: The development of semirigid and flexible ureteroscopes has permitted easier access to calculi throughout the urinary tract. We compared the use of semirigid and flexible ureteroscopy for the management of shockwave lithotripsy-refractory, isolated renal pelvic calculi by evaluating stone-free rates, operating room times, and associated complications. PATIENTS AND METHODS: Ureteroscopic stone treatment was attempted in 47 patients with isolated renal pelvic stones between November 2008 and December 2010. The procedures were performed under general anesthesia. Semirigid ureteroscopy was routinely performed in all patients. If the stones were accessible in the renal pelvis with the semirigid ureteroscope (S-URS), they were then treated with the holmium:yttrium-aluminum-garnet (Ho:YAG) laser through S-URS under direct vision. If the stones were not accessible, flexible ureteroscopy was then performed. Preoperative, operative, and postoperative data were retrospectively analyzed. RESULTS: In 25 of 47 patients, renal pelvic stones were accessible with S-URS, and the stones were fragmented with the Ho:YAG laser using S-URS. In the remaining 22 patients, the stones were accessed with the flexible ureteroscope (F URS), and the fragmentation of stones was performed with the Ho:YAG laser using the F-URS. There were no significant differences in age, body mass index, grade of hydronephrosis, mean stone size, and stone laterality among the two groups. The mean operative times were 71.90 +/- 17.90 minutes in the S-URS group and 93.41 +/- 18.56 minutes in the F-URS group (P=0.001). The stone-free rates at postoperative day 1 and at the 1 month follow-up were 72% and 76% in the S-URS group and 81.8% and 86.4% in the F-URS group, respectively (P=0.861 and P=0.368). We found no significant differences among groups with regard to stone-free rates, complication rates, and hospital lengths of stay. CONCLUSIONS: Although it is well known that flexible ureteroscopy permits a detailed caliceal examination and therapeutic interventions, semirigid ureteroscopy is also often another sufficient means of reaching the renal pelvis in selected patients. PMID- 22304425 TI - Vibrational and electronic spectroscopy of neutral antimony coordination compounds of the 1,3-dithiole-2-thione-4,5-dithiolate (dmit). AB - The S 1s X-ray absorption near edge structure (XANES) and X-ray photoelectron spectra (XPS) of the neutral complexes [SbL(dmit)] (L = Br or I; dmit =1,3 dithiole-2-thione-4,5-dithiolate) have been measured using tunable synchrotron radiation. The valence shell electronic excitation by ultraviolet-visible (UV vis) spectroscopy and the infrared vibrational spectra are presented and analyzed. The UV-vis results lead to an assignment of bands at 400 nm as pi(Sm) > pi*(C?S), where S(m) is the thiolate sulfur. The corresponding S 1s -> pi*(C?S) transition was identified at 2468.3 eV. Ab initio calculations, within the improved virtual orbital (IVO) method, carried out with the GSCF3 program, were applied to establish a complete and accurate spectral assignment. It has been the first attempt to apply such methodology for dmit coordination compounds, and very consistent results were obtained. PMID- 22304426 TI - Development of a problematic mobile phone use scale for Turkish adolescents. AB - Abstract The aim of this study was to evaluate the psychometric properties of the Problematic Mobile Phone Use Scale (PMPUS) for Turkish Adolescents. The psychometric properties of PMPUS were tested in two separate sample groups that consisted of 950 Turkish high school students. The first sample group (n=309) was used to determine the factor structure of the scale. The second sample group (n=461) was used to test data conformity with the identified structure, discriminant validity and concurrent scale validity, internal consistency reliability calculations, and item statistics calculations. The results of exploratory factor analyses indicated that the scale had three factors: interference with negative effect, compulsion/persistence, and withdrawal/tolerance. The results showed that item and construct reliability values yielded satisfactory rates in general for the three-factor construct. On the other hand, the average variance extracted value remained below the scale value for three subscales. The scores for the scale significantly correlated with depression and loneliness. In addition, the discriminant validity value was above the scale in all sub-dimensions except one. Based on these data, the reliability of the PMPUS scale appears to be satisfactory and provides good internal consistency. Therefore, with limited exception, the PMPUS was found to be reliable and valid in the context of Turkish adolescents. PMID- 22304427 TI - Design, preparation, and study of catalytic gated baskets. AB - We report a diastereoselective synthetic method to obtain a family of catalytic molecular baskets containing a spacious cavity (~570 A(3)). These supramolecular catalysts were envisioned, via the process of gating, to control the access of substrates to the embedded catalytic center and thereby modulate the outcome of chemical reactions. In particular, gated basket 1 comprises a porphyrin "floor" fused to four phthalimide "side walls" each carrying a revolving aromatic "gate". With the assistance of (1)H NMR and UV-vis spectroscopy, we demonstrated that the small 1-methylimidazole guest (12, 94 A(3)) would coordinate to the interior while the larger 1,5-diadamantylimidazole guest (14, 361 A(3)) is relegated to the exterior of basket Zn(II)-1. Subsequently, we examined the epoxidation of differently sized and shaped alkenes 18-21 with catalytic baskets 12(in)-Mn(III) 1 and 14(out)-Mn(III)-1 in the presence of the sacrificial oxidant iodosylarene. The epoxidation of cis-stilbene occurred in the cavity of 14(out)-Mn(III)-1 and at the outer face of 12(in)-Mn(III)-1 with the stereoselectivity of the two transformations being somewhat different. Importantly, catalytic basket 14(out) Mn(III)-1 was capable of kinetically resolving an equimolar mixture of cis-2 octene 20 and cis-cyclooctene 21 via promotion of the transformation in its cavity. PMID- 22304430 TI - Role of the helical structure of the N-terminal region of Plasmodium falciparum merozoite surface protein 2 in fibril formation and membrane interaction. AB - Merozoite surface protein 2 (MSP2), an abundant glycosylphosphatidylinositol anchored protein on the surface of Plasmodium falciparum merozoites, is a promising malaria vaccine candidate. MSP2 is intrinsically disordered and forms amyloid-like fibrils in solution under physiological conditions. The 25 N terminal residues (MSP2(1-25)) play an important role in both fibril formation and membrane binding of the full-length protein. In this study, the fibril formation and solution structure of MSP2(1-25) in the membrane mimetic solvents sodium dodecyl sulfate (SDS), dodecylphosphocholine (DPC), and trifluoroethanol (TFE) have been investigated by transmission electronic microscopy, turbidity, thioflavin T fluorescence, circular dichroism (CD), and nuclear magnetic resonance (NMR) spectroscopy. Turbidity data showed that the aggregation of MSP2(1-25) was suppressed in the presence of membrane mimetic solvents. CD spectra indicated that helical structure in MSP2(1-25) was stabilized in SDS and DPC micelles and in high concentrations of TFE. The structure of MSP2(1-25) in 50% aqueous TFE, determined using NMR, showed that the peptide formed an amphipathic helix encompassing residues 10-24. Low concentrations of TFE favored partially folded helical conformations, as demonstrated by CD and NMR, and promoted MSP2(1-25) fibril formation. Our data suggest that partially folded helical conformations of the N-terminal region of MSP2 are on the pathway to amyloid fibril formation, while higher degrees of helical structure stabilized by high concentrations of TFE or membrane mimetics suppress self-association and thus inhibit fibril formation. The roles of the induced helical conformations in membrane interactions are also discussed. PMID- 22304431 TI - Early action and gesture "vocabulary" and its relation with word comprehension and production. AB - Data from 492 Italian infants (8-18 months) were collected with the parental questionnaire MacArthur Bates Communicative Development Inventories to describe early actions and gestures (A-G) "vocabulary" and its relation with spoken vocabulary in both comprehension and production. A-G were more strongly correlated with word comprehension than word production. A clear developmental pattern for the different types of A-G was found. These findings are similar to those of different Western languages, indicating a common biological and cultural basis. The analysis of individual A-G and their relations with early words with a related meaning showed interesting similarities between the production of A-G with and without object manipulation and the comprehension and production of corresponding words. Results indicate that the transition from A-G to spoken language is mediated by word comprehension. PMID- 22304432 TI - Fibroblast growth factor-2-induced cardioprotection against myocardial infarction occurs via the interplay between nitric oxide, protein kinase signaling, and ATP sensitive potassium channels. AB - Fibroblast growth factor-2 (FGF2) protects the heart from ischemia-reperfusion (I R) injury via a vast network of protein kinases. In the heart, downstream effectors of these FGF2-triggered signals have not yet been identified. It is hypothesized that nitric oxide (NO) signaling and ATP-sensitive potassium (K(ATP)) channel activity are key effectors of protein kinases activated by FGF2 mediated cardioprotection. Hearts with a cardiac-specific overexpression of FGF2 (FGF2 Tg) were subjected to I-R injury in the absence or the presence of selective inhibitors of NO synthase (NOS) isoforms or sarcolemmal (sarcK(ATP)) and mitochondrial (mitoK(ATP)) K(ATP) channels. Multiple NOS isoforms are necessary for FGF2-mediated cardioprotection, and nitrite levels are significantly reduced in FGF2 Tg hearts upon inhibition of protein kinase C or mitogen-activated protein kinases. Likewise, sarcK(ATP) and mitoK(ATP) channels are important for cardioprotection elicited by endogenous FGF2. These findings suggest that FGF2-induced cardioprotection occurs via protein kinase-NOS pathways as well as K(ATP) channel activity. PMID- 22304433 TI - Diagnostics of autoimmune bullous diseases in German dermatology departments. AB - BACKGROUND: No consistent data are available on the currently employed diagnostic tools for autoimmune bullous diseases in Germany. The aim of this survey was to describe currently performed diagnostic methods for bullous autoimmune diseases in German dermatology departments. METHODS: A standardized questionnaire evaluated the available diagnostic methods i. e. direct immunofluorescence microscopy (IFM), indirect IFM, commercial ELISA systems, and non-commercial serological tests as well as the number of samples per year in all 34 university and 39 non-university dermatology departments. RESULTS: The overall return rate was 89 %, 100 % and 79 % for the university and non-university departments, respectively. Direct IFM was the most frequently used method and was applied in 98 % of the responding departments. In 74 % of the responding departments, indirect IFM was used mainly on monkey esophagus and human salt-split skin. Commercial ELISA systems were employed in 58 % of the clinics; all of them used anti-desmoglein ELISA, while anti-BP180 and anti-BP230 ELISA were established in 49 % and 48 % of departments, respectively. Non-commercial analytic methods were only performed in 22 % of the departments. CONCLUSIONS: The high return rate of this survey allows a relatively precise description of the current diagnostic methods used in German dermatology departments. Standard diagnostic tests are available nationwide and in bullous pemphigoid and pemphigus, the antigen specific detection of autoantibodies is routinely performed in half of the departments. Rare disorders may be diagnosed by cooperation with some specialized centers. PMID- 22304434 TI - Extinction reveals that primary sensory cortex predicts reinforcement outcome. AB - Primary sensory cortices are traditionally regarded as stimulus analysers. However, studies of associative learning-induced plasticity in the primary auditory cortex (A1) indicate involvement in learning, memory and other cognitive processes. For example, the area of representation of a tone becomes larger for stronger auditory memories and the magnitude of area gain is proportional to the degree that a tone becomes behaviorally important. Here, we used extinction to investigate whether 'behavioral importance' specifically reflects a sound's ability to predict reinforcement (reward or punishment) vs. to predict any significant change in the meaning of a sound. If the former, then extinction should reverse area gains as the signal no longer predicts reinforcement. Rats (n = 11) were trained to bar-press to a signal tone (5.0 kHz) for water-rewards, to induce signal-specific area gains in A1. After subsequent withdrawal of reward, A1 was mapped to determine representational areas. Signal-specific area gains, estimated from a previously established brain-behavior quantitative function, were reversed, supporting the 'reinforcement prediction' hypothesis. Area loss was specific to the signal tone vs. test tones, further indicating that withdrawal of reinforcement, rather than unreinforced tone presentation per se, was responsible for area loss. Importantly, the amount of area loss was correlated with the amount of extinction (r = 0.82, P < 0.01). These findings show that primary sensory cortical representation can encode behavioral importance as a signal's value to predict reinforcement, and that the number of cells tuned to a stimulus can dictate its ability to command behavior. PMID- 22304436 TI - Inhibition of copper uptake in yeast reveals the copper transporter Ctr1p as a potential molecular target of saxitoxin. AB - Saxitoxin is a secondary metabolite produced by several species of dinoflagellates and cyanobacteria which targets voltage-gated sodium and potassium channels in higher vertebrates. However, its molecular target in planktonic aquatic community members that co-occur with the toxin producers remains unknown. Previous microarray analysis with yeast identified copper and iron-homeostasis genes as being differentially regulated in response to saxitoxin. This study sought to identify the molecular target in microbial cells by comparing the transcriptional profiles of key copper and iron homeostasis genes (CTR1, FRE1, FET3, CUP1, CRS5) in cells exposed to saxitoxin, excess copper, excess iron, an extracellular Cu(I) chelator, or an intracellular Cu(I) chelator. Protein expression and localization of Ctr1p (copper transporter), Fet3p (multicopper oxidase involved in high-affinity iron uptake), and Aft1p (iron regulator) were also compared among treatments. Combined transcript and protein profiles suggested saxitoxin inhibited copper uptake. This hypothesis was confirmed by intracellular Cu(I) imaging with a selective fluorescent probe for labile copper. On the basis of the combined molecular and physiological results, a model is presented in which the copper transporter Ctr1p serves as a molecular target of saxitoxin and these observations are couched in the context of the eco evolutionary role this toxin may serve for species that produce it. PMID- 22304437 TI - Isolation of oligotrophic yeasts from supraglacial environments of different altitude on the Gulkana Glacier (Alaska). AB - Psychrophilic yeasts have been isolated from supra- and subglacial ice at many sites worldwide. To understand the ecology of psychrophilic yeasts on glaciers, we focused on their adaptation to wide range of nutrient concentrations and their distribution with altitude on the Gulkana Glacier in Alaska. We found various culturable psychrophilic yeasts on the ice surfaces of the glacier, and 11 species were isolated with incubation at 4 degrees C in four different dilutions of agar medium. Some of our isolated species (Rhodotorula psychrophenolica, Rhodotorula aff. psychrophenolica, Rhodotorula glacialis, and Basidiomycota sp. 1) can grow on the low dissolved organic matter (DOC) concentrations medium (7.6 mg L(-1)) which is close to the typical level of supraglacial melt water, suggesting that these species can inhabit in any supraglacial meltwater. Otherwise, most of other species were isolated only from higher DOC concentration medium (183 mg L(-1) -18.3 g L(-1)), suggesting that these are inhabitant around the cryoconite, because DOC concentrations in melted surface-ice contained cryoconite is much higher than in melted water. Similarity of altitudinal distribution between culturable yeast and algal biomass suggests that the ecological role played by the cold-adapted yeasts is as organic matter decomposers and nutrient cyclers in glacier ecosystem. PMID- 22304438 TI - Teleophthalmology assessment of diabetic retinopathy fundus images: smartphone versus standard office computer workstation. AB - PURPOSE: To evaluate the diagnostic capability of a smartphone handset compared with a standard office computer workstation for teleophthalmology fundus photo assessments of diabetic retinopathy. METHODS: Eligible, consenting participants' fundus images were acquired using a non-mydriatic camera. These images along with other medical data were transmitted 20 miles away through the Internet (gold standard) and also through an iPhone((r)) (Apple, Cupertino, CA) to two ophthalmologists, who independently compared the images. RESULTS: The kappa coefficient between the gold standard workstation display and iPhone images to detect retinopathy-related changes for both readers was more than 0.9. The image quality of the iPhone was scored high by the ophthalmologists. CONCLUSIONS: Ophthalmic images transmitted through both smartphone and Internet techniques match well with each other. Despite current limitations, smartphones could represent as a tool for fundus photo assessments of diabetic retinopathy. Further studies are needed to investigate the economic and clinical feasibility of smartphones in ophthalmology. PMID- 22304439 TI - Transfer of information from personal health records: a survey of veterans using My HealtheVet. AB - OBJECTIVE: Personal health records provide patients with ownership of their health information and allow them to share information with multiple healthcare providers. However, the usefulness of these records relies on patients understanding and using their records appropriately. My HealtheVet is a Web-based patient portal containing a personal health record administered by the Veterans Health Administration. The goal of this study was to explore veterans' interest and use of My HealtheVet to transfer and share information as well as to identify opportunities to increase veteran use of the My HealtheVet functions. MATERIALS AND METHODS: Two waves of data were collected in 2010 through an American Customer Satisfaction Index Web-based survey. A random sample of veterans using My HealtheVet was invited to participate in the survey conducted on the My HealtheVet portal through a Web-based pop-up browser window. RESULTS: Wave One results (n=25,898) found that 41% of veterans reported printing information, 21% reported saving information electronically, and only 4% ever sent information from My HealtheVet to another person. In Wave Two (n=18,471), 30% reported self entering medication information, with 18% sharing this information with their Veterans Affairs (VA) provider and 9.6% sharing with their non-VA provider. CONCLUSION: Although veterans are transferring important medical information from their personal health records, increased education and awareness are needed to increase use. Personal health records have the potential to improve continuity of care. However, more research is needed on both the barriers to adoption as well as the actual impact on patient health outcomes and well-being. PMID- 22304440 TI - The patient-centered medical home and health information technology. AB - OBJECTIVE: To demonstrate that concepts of patient-centeredness and technology centeredness must work together within the context of the transformation to the patient-centered medical home (PCMH), a primary care model that emphasizes coordinated, comprehensive, accessible, and cost-effective care. MATERIALS AND METHODS: Information in this article was gathered from a workshop on the Medical Home in Alexandria, VA in June 2010 that brought together civilian and military medical providers, researchers, and other stakeholders in PCMH to discuss their experiences in transitioning from traditional primary care to PCMH in addition to a literature review of articles from medical journals. RESULTS: Patient centeredness is often only vaguely defined as being in opposition to provider centered or technology-centered. Our analysis shows that focusing on either technological improvements or enhancing patient-centered care will not improve the fragmented healthcare system in the United States. We argue that these two concepts are not incompatible as sometimes believed, but rather it is critical that we recognize they must work together in routine practices in order to truly improve the state of healthcare. CONCLUSION: Health information technology (HIT) supports many of the core principles of PCMH, but there are still several challenges as not all technologies have functionalities yet that facilitate the model. We suggest patient-centeredness be one of the main concepts that drives the redesign and implementation of new health technologies in primary care. It is no longer about just implementing new technologies; these technologies must enhance patient-provider relationships, communication, access, and patients' engagement in their own care. PMID- 22304441 TI - Protein structural dynamics of photoactive yellow protein in solution revealed by pump-probe X-ray solution scattering. AB - Photoreceptor proteins play crucial roles in receiving light stimuli that give rise to the responses required for biological function. However, structural characterization of conformational transition of the photoreceptors has been elusive in their native aqueous environment, even for a prototype photoreceptor, photoactive yellow protein (PYP). We employ pump-probe X-ray solution scattering to probe the structural changes that occur during the photocycle of PYP in a wide time range from 3.16 MUs to 300 ms. By the analysis of both kinetics and structures of the intermediates, the structural progression of the protein in the solution phase is vividly visualized. We identify four structurally distinct intermediates and their associated five time constants and reconstructed the molecular shapes of the four intermediates from time-independent, species associated difference scattering curves. The reconstructed structures of the intermediates show the large conformational changes such as the protrusion of N terminus, which is restricted in the crystalline phase due to the crystal contact and thus could not be clearly observed by X-ray crystallography. The protrusion of the N-terminus and the protein volume gradually increase with the progress of the photocycle and becomes maximal in the final intermediate, which is proposed to be the signaling state. The data not only reveal that a common kinetic mechanism is applicable to both the crystalline and the solution phases, but also provide direct evidence for how the sample environment influences structural dynamics and the reaction rates of the PYP photocycle. PMID- 22304442 TI - Blood graft lymphocyte subsets after plerixafor injection in non-Hodgkin's lymphoma patients mobilizing poorly with chemotherapy plus granulocyte-colony stimulating factor. AB - BACKGROUND: A combination of chemotherapy plus granulocyte-colony-stimulating factor (G-CSF) (chemomobilization) is commonly used to mobilize CD34+ cells to circulation. Plerixafor, a chemokine CXCR4 antagonist, increases the mobilization of CD34+ cells and may also have effect on graft composition. STUDY DESIGN AND METHODS: We have analyzed lymphocyte subsets in grafts collected on the next morning after plerixafor injection in 13 chemomobilized patients with non Hodgkin's lymphoma (NHL) mobilizing poorly. As controls we had the first leukapheresis products from 11 NHL patients mobilized with chemotherapy plus G CSF. The analyses were performed from cryopreserved apheresis products. RESULTS: The median counts of both total CD3+ T cells and natural killer (NK) cells (CD3 CD16/56+) in the graft were significantly higher in plerixafor-treated group compared to the control group. Both helper T-lymphocytes (CD3+CD4+) and suppressor T-lymphocytes (CD3+CD8+) were significantly increased in the plerixafor-treated group so that CD4+/CD8+ ratio in the graft did not differ between the groups. CD19+ cells were evident only at very small amounts in few patients in both groups, and the CD34+ cell content of the graft did not differ between the groups. Engraftment after high-dose therapy was comparable between the groups. CONCLUSION: Plerixafor added to chemomobilization in poor mobilizers seems to mobilize more T cells and NK cells than chemomobilization. Larger patient numbers and longer follow-up is needed in regard to evaluate posttransplant complications and risk of relapse in patients receiving plerixafor due to poor mobilization. PMID- 22304443 TI - Agreement between colposcopic impression and histological diagnosis among human papillomavirus type 16-positive women: a clinical trial using dynamic spectral imaging colposcopy. AB - OBJECTIVE: To investigate the agreement between conventional colposcopic impression, dynamic spectral imaging (DSI) colposcopy and histology, for human papillomavirus type 16-positive (HPV16(+)) and non-16 high-risk (hr) HPV(+) women. DESIGN: Prospective, comparative, multicentre clinical trial. SETTING: Three colposcopy clinics in the Netherlands. POPULATION: Women (n = 177) aged 18 years or over with an intact cervix, referred for colposcopy. METHODS: The colposcopist graded the lesion by using the DSI colposcope as a regular video colposcope. Subsequently the DSI impression was displayed and biopsies were taken from all abnormal areas as well as from a random (normal) site. A cervical smear was taken for HPV typing. MAIN OUTCOME MEASURES: Histologically confirmed high grade cervical intraepithelial neoplasia or cancer (CIN2(+)), positive for HPV16 or for any other hrHPV type. RESULTS: The DSI colposcope identified more CIN2(+) cervical lesions among HPV16(+) women than in non-16 hrHPV(+) women (P = 0.032 regardless of final histology and P = 0.009 among women with CIN2(+)). Consequently, the sensitivity of the DSI colposcope for detecting CIN2(+) lesions was higher in HPV16(+) women than in non-16 hrHPV(+) women (97% versus 74%, P = 0.009). No such differences were seen for the colposcopist impression. In addition, mainly smaller cervical lesions are missed by the colposcopist. CONCLUSIONS: The sensitivity of DSI colposcopy for CIN2(+) is higher in HPV16(+) than in non-16 hrHPV(+) women. Furthermore, regardless of HPV16 status, the sensitivity of DSI for CIN2(+) is higher than that of the colposcopist, probably because colposcopists tend to miss smaller cervical lesions. PMID- 22304444 TI - Solid state spectroelectrochemistry of redox reactions in polypyrrole/oxide molecular heterojunctions. AB - To understand the mechanism of bias-induced resistance switching observed in polypyrrole (PPy) based solid state junctions, in situ UV-vis absorption spectroscopy was employed to monitor oxidation states within PPy layers in solution and in PPy/metal oxide junctions. For PPy layers in acetonitrile, oxidation led primarily to cationic polaron formation, while oxidation in 0.1 M NaOH in H(2)O resulted in imine formation, caused by deprotonation of polarons. On the basis of these results in solution, spectroelectrochemistry was used to monitor bias-induced formation of polarons and imines in PPy layers incorporated into solid state carbon/PPy/Al(2)O(3)/Pt junctions. A positive bias on the carbon electrode caused PPy oxidation, with the formation of polaron and imine species strongly dependent on the surrounding environment. The spectral changes associated with polarons or imines were stable for at least several hours after the applied bias, while a negative bias reversed the absorbance changes back to the initial PPy spectrum. These results indicate that PPy can be oxidized in nominally solid state devices, and the formation of stable polarons is dependent on the tendency for deprotonation of the polaron to the imine. Since PPy conductivity depends strongly on the polaron concentration, monitoring its concentration is critical to determining resistance switching mechanisms. Furthermore, the importance of ion mobility and OH(-) generation through H(2)O reduction at the Pt contact are discussed. PMID- 22304445 TI - Multiple pilomatricomas in Kabuki syndrome. AB - Pilomatricoma is a benign tumor of the hair matrix cell that presents predominantly in childhood. Although pilomatricoma occurs spontaneously, multiple pilomatricomas have been described in association with several inherited syndromes. We report on a 28-year-old man with Kabuki syndrome with three pilomatricomas in his head and thigh. Although several reports describe multiple pilomatricomas associated with Turner syndrome, there are no reports of multiple pilomatricomas combined with Kabuki syndrome. Ectodermal abnormalities such as hair abnormality and hirsutism are symptoms of Kabuki syndrome, and pilomatricomas are frequently associated with the mutations of beta-catenin in hair follicle development. The predisposition of pilomatricomas may be not merely a coincidental finding, but an added association with Kabuki syndrome. PMID- 22304446 TI - Adsorption behavior of EDTA-graphene oxide for Pb (II) removal. AB - Chelating groups are successfully linked to graphene oxide (GO) surfaces through a silanization reaction between N-(trimethoxysilylpropyl) ethylenediamine triacetic acid (EDTA-silane) and hydroxyl groups on GO surface. EDTA-GO was found to be an ideal adsorbent for Pb(II) removal with a higher adsorption capacity. EDTA-modification enhances the adsorption capacity of GO because of the chelating ability of ethylene diamine triacetic acid. This study investigates the adsorption and desorption behaviors of heavy metal cations and the effects of solution conditions such as pH on Pb(II) removal. The adsorption capacity for Pb(II) removal was found to be 479 +/- 46) mg/g at pH 6.8, and the adsorption process was completed within 20 min. The Langmuir adsorption model agrees well with the experimental data. The experimental results suggest that EDTA-GO can be reused after washed with HCl, suggesting potential applications in the environmental cleanup. PMID- 22304448 TI - Crocodile tears syndrome after vestibular schwannoma surgery. AB - OBJECT: Crocodile tears syndrome (CTS) is a lacrimal hypersecretion disorder characterized by excessive tearing with gustatory stimulation while eating, drinking, or smelling food. Surgeons tend to overlook CTS after vestibular schwannoma (VS) surgery because its symptoms are less obvious compared with facial paralysis. The authors aim to elucidate the precise incidence and the detailed natural course of CTS after VS surgery. METHODS: This study included 128 consecutive patients with unilateral VSs resected via a retrosigmoid, lateral suboccipital approach. Clinical information on the patients was obtained by retrospective chart review. The presence of, time of onset of, and recovery of patients from CTS were obtained from the chart or evaluated from the most recent outpatient visit. RESULTS: A total of 14 patients (10.9%) developed CTS. Motor function of the facial nerve at discharge was statistically related to the occurrence of CTS (p < 0.001). The odds ratio of House-Brackmann Grade 4 compared with Grade 1 was 86.4 (p < 0.001). A bimodal distribution of CTS onset was observed, with a mean onset of 6.1 +/- 4.0 months after resection. The CTS improved in 10 patients (71%) at various intervals, whereas CTS resolved in only 7 patients (50%) at a mean interval of 10.9 +/- 7.9 months. The mean interval to recovery in the early-onset group was 9.7 +/- 7.9 months, and it was 18 months in the late-onset group; the mean is given +/- SD throughout. CONCLUSIONS: The occurrence of CTS following VS surgery was more common than expected; however, a surgical procedure intended to protect the functioning of the facial nerve appears to be conducive to reduction of the occurrence of CTS. To reduce the distress caused by CTS, all patients should be given sufficient information and provide their informed consent prior to surgery. PMID- 22304447 TI - Treatment and outcomes of acute intracranial vertebrobasilar artery occlusion: one institution's experience. AB - OBJECT: The treatment of acute intracranial vertebrobasilar artery occlusion (VBO) has been described but often with poor results. The authors of this study set out to evaluate their institution's outcomes following multimodal treatment of VBO. METHODS: They retrospectively reviewed their endovascular database for all patients treated for acute intracranial VBO between December 2004 and June 2010. Twenty-four patients were identified. Two patients were excluded from evaluation-one because of incomplete medical records and one because the etiology was basilar stenosis and not stroke. Occlusion location, hypercoagulable causes, time to endovascular treatment, time to revascularization, comorbidities, devices used, procedural anticoagulation, and outcomes were analyzed. RESULTS: Among the 22 eligible study patients, the mean National Institutes of Health Stroke Scale (NIHSS) score at presentation was 15.3. The mean time from presentation to initiation of the endovascular procedure was 4.77 hours. The mean time for recanalization from the start of angiography was 1.63 hours. In 16 patients (73%), revascularization was successful (Thrombolysis in Myocardial Infarction [TIMI] score of 2 or 3). Thirteen (59%) of the 22 patients were discharged to home or a rehabilitation facility. One patient was transferred to a chronic care facility. The overall survival rate was 64%. The average NIHSS score for the 14 surviving patients at discharge was 3.9. At the follow-up (average 14.5 months, range 1-58 months), 10 patients (71%) had achieved good outcomes (modified Rankin Scale [mRS] score <= 2) and 4 (29%) had poor outcomes (mRS Score 3-6). CONCLUSIONS: Published case series have historically shown poor outcomes and high mortality rates in association with the treatment of acute VBO, prompting surgeons to be less aggressive in the treatment of this disease than they might be otherwise. Data in this series show that the revascularization of posterior circulation occlusions is feasible and that good outcomes and lower mortality rates with newer endovascular technologies are possible, and thus more prompt and aggressive treatment of this disease may be warranted. PMID- 22304449 TI - A novel technique of multiple-site epidural blood patch administration for the treatment of cerebrospinal fluid hypovolemia. AB - OBJECT: An epidural blood patch (EBP) is a widely accepted standard procedure to treat CSF hypovolemia, especially when the epidural CSF leak is detected by spinal MRI or CT myelography (CTM). In quite a few cases, however, the leaked CSF is spread over a large area along the spinal epidural space, making it difficult for the surgeon to clearly identify the true leakage points. In such cases, autologous blood can be infused at multiple spinal levels with multiple entries. In this paper, the authors have devised a new multiple-site EBP method with a single lumbar entry point by way of using an intravenous catheter as a slidable device for continuous infusion. In this report, they introduce this new, single entry, continuous multiple-site EBP administration technique and report some of the results that they have obtained. METHODS: An EBP was applied via an epidural catheter in 5 patients with spontaneous CSF hypovolemia (3 men and 2 women; mean age 47.2 years, range 34-65 years). The detection of an epidural CSF leak was based on MRI and/or CTM findings. In all cases, however, the leakage sites could not be identified clearly. The main symptoms of these patients were recurrent spontaneous chronic subdural hematoma with orthostatic headache (3 patients) and orthostatic headache only (2 patients). All patients underwent surgery in the prone position on an angiography table, and biplane fluoroscopy was used for accurate manipulation. After administration of a local anesthetic, the authors inserted a 4-Fr short sheath (which is standard in angiography) through the lumbar interlaminar window and placed it in the dorsal epidural space. They then introduced a 4.2-Fr straight catheter through the sheath and navigated it upward along a 35-gauge guidewire whose tip was moved upward beyond the cranial end of the detected CSF leakage. Blood was obtained from each patient from a previously secured venous entry on the forearm, and it was injected slowly into the epidural catheter. Each time, the authors tried to infuse as much autologous blood as possible into the epidural space, while moving the catheter gradually in the caudal direction in response to the patient's expression of pain. RESULTS: In all 3 cases of chronic subdural hematoma, its recurrence was prevented. In 1 patient, the orthostatic headache disappeared completely, and it was relieved in the other 4 patients. CONCLUSIONS: An efficient treatment option for CSF hypovolemia is provided by the new application method of EBP with the aid of an intravenous catheter as a slidable device, which enables infusion of a sufficient amount of autologous blood into multiple epidural areas with a single lumbar entry point. PMID- 22304450 TI - Rates and predictors of long-term seizure freedom after frontal lobe epilepsy surgery: a systematic review and meta-analysis. AB - OBJECT: Frontal lobe epilepsy (FLE) is the second-most common focal epilepsy syndrome, and seizures are medically refractory in many patients. Although various studies have examined rates and predictors of seizure freedom after resection for FLE, there is significant variability in their results due to patient diversity, and inadequate follow-up may lead to an overestimation of long term seizure freedom. METHODS: In this paper the authors report a systematic review and meta-analysis of long-term seizure outcomes and predictors of response after resection for intractable FLE. Only studies of at least 10 patients examining seizure freedom after FLE surgery with postoperative follow-up duration of at least 48 months were included. RESULTS: Across 1199 patients in 21 studies, the overall rate of postoperative seizure freedom (Engel Class I outcome) was 45.1%. No trend in seizure outcomes across all studies was observed over time. Significant predictors of long-term seizure freedom included lesional epilepsy origin (relative risk [RR] 1.67, 95% CI 1.36-28.6), abnormal preoperative MRI (RR 1.64, 95% CI 1.32-2.08), and localized frontal resection versus more extensive lobectomy with or without an extrafrontal component (RR 1.71, 95% CI 1.26-2.43). Within lesional FLE cases, gross-total resection led to significantly improved outcome versus subtotal lesionectomy (RR 1.99, 95% CI 1.47-2.84). CONCLUSIONS: These findings suggest that FLE patients with a focal and identifiable lesion are more likely to achieve seizure freedom than those with a more poorly defined epileptic focus. While seizure freedom can be achieved in the surgical treatment of medically refractory FLE, these findings illustrate the compelling need for improved noninvasive and invasive localization techniques in FLE. PMID- 22304451 TI - Coexistence of intracranial aneurysm in 800 patients with surgically confirmed pituitary adenoma. AB - OBJECT: The purpose of this study was to assess factors associated with intracranial aneurysm (IA) in patients with pituitary adenoma (PA). In addition, these patients were compared with a control group from the general patient population in terms of the age-matched prevalence rate and the pattern of distribution of IA. METHODS: The authors retrospectively reviewed 800 patients who received transsphenoidal surgery for PA and 3850 control patients from the general patient population who were evaluated for routine health care at the authors' institution between 2004 and 2010. All patients underwent MR imaging and MR angiography. Hormone assessment and pathological examination performed using immunohistochemical (IHC) staining were completed for patients with PA. RESULTS: Coexistence of IA in patients with PA was detected in 18 patients (2.3%). Multivariate analysis showed that age (p = 0.04) and cavernous sinus invasion (p < 0.001) were correlated with the increased incidence of IA, but hormone type, IHC staining, and sex were not associated. An age-matched comparison of the prevalence of IA showed an increased prevalence in patients with PA compared with the controls (p = 0.014), and when categorized according to age by decade, the 6th decade was significantly different (p = 0.039). However, the intracranial distribution pattern of IA did not demonstrate a significant difference. CONCLUSIONS: Older age and the existence of a cavernous sinus invasion were correlated with increased incidence of IA in patients with PA. An age-matched comparison showed an increased incidence of IA in patients with PA than in the controls. PMID- 22304452 TI - Utility of presurgical navigated transcranial magnetic brain stimulation for the resection of tumors in eloquent motor areas. AB - OBJECT: Navigated transcranial magnetic stimulation (nTMS) is a newly evolving technique. Despite its supposed purpose (for example, preoperative central region mapping), little is known about its accuracy compared with established modalities like direct cortical stimulation (DCS) and functional MR (fMR) imaging. Against this background, the authors performed the current study to compare the accuracy of nTMS with DCS and fMR imaging. METHODS: Fourteen patients with tumors in or close to the precentral gyrus were examined using nTMS for motor cortex mapping, as were 12 patients with lesions in the subcortical white matter motor tract. Moreover, preoperative fMR imaging and intraoperative mapping of the motor cortex were performed via DCS, and the outlining of the motor cortex was compared. RESULTS: In the 14 cases of lesions affecting the precentral gyrus, the primary motor cortex as outlined by nTMS correlated well with that delineated by intraoperative DCS mapping, with a deviation of 4.4 +/- 3.4 mm between the two methods. In comparing nTMS with fMR imaging, the deviation between the two methods was much larger: 9.8 +/- 8.5 mm for the upper extremity and 14.7 +/- 12.4 mm for the lower extremity. In 13 of 14 cases, the surgeon admitted easier identification of the central region because of nTMS. The procedure had a subjectively positive influence on the operative results in 5 cases and was responsible for a changed resection strategy in 2 cases. One of 26 patients experienced nTMS as unpleasant; none found it painful. CONCLUSIONS: Navigated TMS correlates well with DCS as a gold standard despite factors that are supposed to contribute to the inaccuracy of nTMS. Moreover, surgeons have found nTMS to be an additional and helpful modality during the resection of tumors affecting eloquent motor areas, as well as during preoperative planning. PMID- 22304453 TI - Synthesis and in vitro antimicrobial activity of new 4-phenyl-5-methyl-4H-1,2,4 triazole-3-thione derivatives. AB - This study presents the synthesis, spectral analysis and antimicrobial evaluation of a new series of substituted 1,2,4-triazole (5a-i) and 1,3,4-thiadiazole derivatives (9a, c, g, h). New compounds were obtained by cyclization reaction of acyl thiosemicarbazide derivatives in the presence of alkaline and acidic media. All synthesized compounds were screened for their in vitro antimicrobial activities. Nine of the compounds had potential activity against Gram-positive bacteria (MIC = 3.91-500 ug/mL). Some compounds showed good activity especially against: Micrococcus luteus ATCC 10240 (MIC = 3.91-31.25 ug/mL), Bacillus subtilis ATCC 6633 (MIC = 15.63- 62.5 ug/mL), and Staphylococcus aureus ATCC 25923 (MIC = 15.63-125 ug/mL). PMID- 22304454 TI - Decomposing the interaction between retention interval and study/test practice: the role of retrievability. AB - Even without feedback, test practice enhances delayed performance compared to study practice, but the size of the effect is variable across studies. We investigated the benefit of testing, separating initially retrievable items from initially nonretrievable items. In two experiments, an initial test determined item retrievability. Retrievable or nonretrievable items were subsequently presented for repeated study or test practice. Collapsing across items, in Experiment 1, we obtained the typical cross-over interaction between retention interval and practice type. For retrievable items, however, the cross-over interaction was quantitatively different, with a small study benefit for an immediate test and a larger testing benefit after a delay. For nonretrievable items, there was a large study benefit for an immediate test, but one week later there was no difference between the study and test practice conditions. In Experiment 2, initially nonretrievable items were given additional study followed by either an immediate test or even more additional study, and one week later performance did not differ between the two conditions. These results indicate that the effect size of study/test practice is due to the relative contribution of retrievable and nonretrievable items. PMID- 22304455 TI - Exciton spin relaxation in colloidal CdSe quantum dots at room temperature. AB - Size dependence of spin dynamics in colloidal CdSe quantum dots (QDs) are investigated with circularly polarized pump-probe transmission spectroscopy at room temperature. The excitation energy is tuned to resonance with the lowest exciton (1S(h)1S(e)) energy of the CdSe QDs. The exciton spin dynamics of CdSe QD with the diameter of 5.2 nm shows monoexponential decay with a typical time constant of about 1-3 ps depending on the excitation energy. For the cases of CdSe QDs with smaller size (with the diameter of 4.0 and 2.4 nm), the exciton spin relaxation shows biexponential decay, a fast component with time constant of several ps and a slow one with time constant of hundreds of ps to nanosecond time scale. The fast spin relaxation arises from the bright-dark transition, i.e., J = +/-1 <-> -/+2 transition. This process is dominated by the hole spin flips, while the electron spin conserves. The slow spin relaxation is attributed to the intralevel exciton transitions (J = +/-1 <-> -/+1 transition), which is relevant to the electron spin flip. Our results indicate that the exciton spin relaxation pathways in CdSe QD are controllable by monitoring the particle size, and polarized pump-probe spectroscopy is proved to be a sensitive method to probe the exciton transition among the fine structures. PMID- 22304456 TI - Upregulation of mucosal 5-HT3 receptors is involved in restoration of colonic transit after pelvic nerve transection. AB - BACKGROUND: Colonic dysfunction occurs after pelvic autonomic nerve damage. The enteric nervous system can compensate. We investigated the role of mucosal serotonin receptors, 5-HT(3) and 5-HT(4) , in the colonic motility restoration over 2 weeks after parasympathetic pelvic nerve transection in a rat model. METHODS: Male Sprague-Dawley rats underwent pelvic nerve transection or sham operation. Colonic transit was expressed as the geometric center of (51) Cr distribution. Mucosal 5-HT(3) and 5-HT(4) receptor expression was evaluated by Western blot. Intraluminal pressure increase was measured after 5-HT(3) (ondansetron) or 5-HT(4) receptor antagonist (GR125487) administration in vitro in sham and denervated distal colons. KEY RESULTS: At 2 weeks, colonic transit in the denervated group was 30% slower compared to the sham group (P < 0.01). At 1 and 2 weeks, 5-HT(3) receptor expression was increased two-fold in the denervated group, compared to shams (P < 0.05). A three-fold smaller dose of ondansetron was required in denervated tissues to inhibit intraluminal pressure rise than in sham colons (P < 0.01). There was no difference in the expression of 5-HT(4) receptor or the response to GR125487 in denervated vs sham colons. CONCLUSIONS & INFERENCES: Colonic motility was restored to approximately 70% normal over 1 week without further improvement at 2 weeks. Enteric nervous system compensated by upregulating mucosal 5-HT(3,) but not 5-HT(4,) receptors. PMID- 22304457 TI - Participation willingness in web surveys: exploring effect of sponsoring corporation's and survey provider's reputation. AB - Prior research involving response rates in Web-based surveys has not adequately addressed the effect of the reputation of a sponsoring corporation that contracts with a survey provider. This study investigates the effect of two factors, namely, the reputation of a survey's provider and the reputation of a survey's sponsoring corporation, on the willingness of potential respondents to participate in a Web survey. Results of an experimental design with these two factors reveal that the sponsoring corporation's and the survey provider's strong reputations can induce potential respondents to participate in a Web survey. A sponsoring corporation's reputation has a greater effect on the participation willingness of potential respondents of a Web survey than the reputation of the survey provider. A sponsoring corporation with a weak reputation who contracts with a survey provider having a strong reputation results in increased participation willingness from potential respondents if the identity of the sponsoring corporation is disguised in a survey. This study identifies the most effective strategy to increase participation willingness for a Web-based survey by considering both the reputations of the sponsoring corporation and survey provider and whether to reveal their identities. PMID- 22304458 TI - Increased susceptibility to metabolic syndrome in adult offspring of angiotensin type 1 receptor autoantibody-positive rats. AB - AIMS: Abnormal fetal and early postnatal growth is closely associated with adult onset metabolic syndrome (MetS). However, the underlying etiological factors remain complex. The presence of the autoantibody against the angiotensin II type 1 receptor (AT1-Ab), a known risk factor for pre-eclampsia, may create a suboptimal intrauterine fetal environment. The current study investigated whether middle-aged offspring of AT1-Ab-positive mothers were prone to metabolic disorder development. RESULTS: The AT1-Abs was detected in placental trophoblastic cells, capillary endothelium, and milk of pregnant rats actively immunized with the second extracellular loop of the AT1 receptor. AT1-Abs in newborn rats induced vasoconstriction, increased intracellular-free Ca(2+) in vitro, and was undetectable 7 weeks later. Immunized group offspring exhibited increased weight variability and insulin resistance at 40 weeks of age under a normal diet, evidenced by elevated fasting serum insulin and homeostasis model assessment score compared with the vehicle control. To further observe metabolic alterations, the offspring were given a high-sugar diet (containing 20% sucrose) 40-48 weeks postnatally. The fasting plasma glucose in immunized group offspring was markedly increased. Concomitantly, these offspring manifested increased visceral adipose tissue, increased fatty liver, increased triglycerides, decreased high-density lipoprotein cholesterol, and decreased adiponectin levels, indicative of MetS. INNOVATION: AT1-Abs could be transferred from mother to offspring via the placenta and milk. Moreover, offspring of an AT1-Ab-positive mother were more vulnerable to MetS development in middle age. CONCLUSION: AT1-Ab positivity of mothers during pregnancy is a previously unrecognized "silent" risk factor for MetS development in their offspring. PMID- 22304460 TI - 1,4-Diazaspiro[2.2]pentanes as a flexible platform for the synthesis of diamine bearing stereotriads. AB - Nitrogen-containing stereotriads occur in a number of biologically active compounds, but general and flexible methods to access these compounds are limited mainly to the manipulation of chiral olefins. An alternative approach is to employ a highly chemo-, regio-, and stereocontrolled allene oxidation that can install a new carbon-heteroatom bond at each of the three original allene carbons. In this paper, an intramolecular/intermolecular allene bis-aziridination is described that offers the potential to serve as a key step for the construction of stereotriads containing vicinal diaminated motifs. The resultant 1,4-diazaspiro[2.2]pentane (DASP) scaffolds contain two electronically differentiated aziridines that undergo highly regioselective ring openings at C1 with a variety of heteroatom nucleophiles to give chiral N,N-aminals. Alternatively, the same DASP intermediate can be induced to undergo a double ring opening reaction at both C1 and C3 to yield vicinal diaminated products corresponding to formal ring opening at C3. The chirality of a propargyl alcohol is easily transferred to the DASP with good fidelity, providing a new paradigm for the construction of enantioenriched nitrogen-containing stereotriads. PMID- 22304461 TI - Specificity of binding of single-stranded DNA-binding protein to its target. AB - Single-stranded DNA-binding proteins (SSBs) bind single-stranded DNA (ssDNA) and participate in all genetic processes involving ssDNA, such as replication, recombination, and repair. Here we applied atomic force microscopy to directly image SSB-DNA complexes under various conditions. We used the hybrid DNA construct methodology in which the ssDNA segment is conjugated to the DNA duplex. The duplex part of the construct plays the role of a marker, allowing unambiguous identification of specific and nonspecific SSB-DNA complexes. We designed hybrid DNA substrates with 5'- and 3'-ssDNA termini to clarify the role of ssDNA polarity on SSB loading. The hybrid substrates, in which two duplexes are connected with ssDNA, were the models for gapped DNA substrates. We demonstrated that Escherichia coli SSB binds to ssDNA ends and internal ssDNA regions with the same efficiency. However, the specific recognition by ssDNA requires the presence of Mg(2+) cations or a high ionic strength. In the absence of Mg(2+) cations and under low-salt conditions, the protein is capable of binding DNA duplexes. In addition, the number of interprotein interactions increases, resulting in the formation of clusters on double-stranded DNA. This finding suggests that the protein adopts different conformations depending on ionic strength, and specific recognition of ssDNA by SSB requires a high ionic strength or the presence of Mg(2+) cations. PMID- 22304462 TI - Atopic dermatitis and allergic rhinitis--do co-effects in therapy exist? AB - Atopic dermatitis and allergic rhinitis frequently appear together in the same patients. The pathogenesis of both disorders is complex and still incompletely understood. Nevertheless, pathophysiological overlaps suggest the existence of potential therapeutic co-effects. While data pointing towards a positive effect of allergen elimination for both diseases is still limited, there is now increasing evidence showing beneficial effects of specific immunotherapy in patients suffering from atopic dermatitis and additional type I allergies. H(1) antihistamines were also found to exert moderate positive effects on the symptoms of atopic dermatitis in single studies. In summary, a limited therapeutic co effect of the above mentioned treatment options can be expected in case of the parallel existence of atopic dermatitis and allergic rhinitis in the same patient. More studies on this issue during the next years are desirable. In addition, a better understanding of the pathophysiology should have a positive impact on the treatment of atopic manifestations such as atopic dermatitis and allergic rhinitis. PMID- 22304463 TI - Lack of association of CYP1A1 polymorphism with prostate cancer susceptibility of Tunisian men. AB - Cytochrome P450 (CYP)1A1 gene polymorphism has been shown to be associated with several diseases. In this study, we evaluated the association between the polymorphism in the cytochrome P-450 (CYP)1A1 (CYP1A1) gene and genetic susceptibility to prostate cancer (PCa) in Tunisian men. One hundred and thirty eight PCa patients and the same number of controls were enrolled in this study. All DNA samples from peripheral blood leucocytes were genotyped for genetic polymorphism of the CYP1A1 gene using the polymerase chain reaction-restriction fragment length polymorphism method. The polymorphism in PCa patients was also analyzed according to age at diagnosis, tobacco use, cancer stage, and grade (Gleason score). The prevalence of CYP1A1 variants (w1m1 and m1m1) was similar in PCa patients and controls (15.22% vs. 17.39%, p=0.624 and 2.17%, respectively). No significant difference in the frequency distribution of CYP1A1 polymorphism was observed between PCa patients and controls. Furthermore, we were unable to demonstrate any significant association between the studied CYP1A1 polymorphism, age, tobacco use, and tumor parameters of aggressiveness at diagnosis. PMID- 22304464 TI - Climatic, biological, and land cover controls on the exchange of gas-phase semivolatile chemical pollutants between forest canopies and the atmosphere. AB - An ecophysiological model of a structured broadleaved forest canopy was coupled to a chemical fate model of the air-canopy exchange of gaseous semivolatile chemicals to dynamically assess the short-term (hours) and medium term (days to season) air-canopy exchange and the influence of biological, climatic, and land cover drivers on the dynamics of the air-canopy exchange and on the canopy storage for airborne semivolatile pollutants. The chemical fate model accounts for effects of short-term variations in air temperature, wind speed, stomatal opening, and leaf energy balance, all as a function of layer in the canopy. Simulations showed the potential occurrence of intense short/medium term re emission of pollutants having log K(OA) up to 10.7 from the canopy as a result of environmental forcing. In addition, relatively small interannual variations in seasonally averaged air temperature, canopy biomass, and precipitation can produce relevant changes in the canopy storage capacity for the chemicals. It was estimated that possible climate change related variability in environmental parameters (e.g., an increase of 2 degrees C in seasonally averaged air temperature in combination with a 10% reduction in canopy biomass due to, e.g., disturbance or acclimatization) may cause a reduction in canopy storage capacity of up to 15-25%, favoring re-emission and potential for long-range atmospheric transport. On the other hand, an increase of 300% in yearly precipitation can increase canopy sequestration by 2-7% for the less hydrophobic compounds. PMID- 22304465 TI - An assessment of thromboelastometry to monitor blood coagulation and guide transfusion support in liver transplantation. AB - BACKGROUND: Rotation thromboelastometry (TEM) has been proposed as a convenient alternative to standard coagulation tests in guiding the treatment of coagulopathy during orthotopic liver transplantation (OLT). This study was aimed at assessing the value of TEM in monitoring blood coagulation and guide transfusion support in OLT. STUDY DESIGN AND METHODS: Standard coagulation and TEM (EXTEM and FIBTEM) tests were performed at four preestablished intraoperative time points in 236 OLTs and prospectively recorded in a dedicated database together with the main operative and transfusion data. Transfusion thresholds were based on standard coagulation tests. Spearman's rank correlation (rho), linear regression, and receiver operating characteristic curves were used when appropriate. RESULTS: EXTEM maximum clot firmness (MCF(EXTEM)) was the TEM variable that best correlated with the platelet (PLT) and fibrinogen levels (rho = 0.62 and rho = 0.69, respectively). MCF(FIBTEM) correlated with fibrinogen level (rho = 0.70). EXTEM clot amplitude at 10 minutes (A10(EXTEM)) was a good linear predictor of MCF(EXTEM) (R(2) =0.93). The cutoff values that best predicted the transfusion threshold for PLTs and fibrinogen were A10(EXTEM) = 35 mm and A10(FIBTEM) = 8 mm. At these values, the negative and positive predictive accuracies of TEM to predict the transfusion thresholds were 95 and 27%, respectively. CONCLUSION: A10(EXTEM) is an adequate TEM variable to guide therapeutic decisions during OLT. Patients with A10(EXTEM) of greater than 35 mm are unlikely to bleed because of coagulation deficiencies, but using A10(EXTEM) of not more than 35 mm as the sole transfusion criterion can lead to unnecessary utilization of PLTs and fibrinogen-rich products. PMID- 22304467 TI - The mind behind the message: advancing theory-of-mind scales for typically developing children, and those with deafness, autism, or Asperger syndrome. AB - Children aged 3-12 years (n = 184) with typical development, deafness, autism, or Asperger syndrome took a series of theory-of-mind (ToM) tasks to confirm and extend previous developmental scaling evidence. A new sarcasm task, in the format of H. M. Wellman and D. Liu's (2004) 5-step ToM Scale, added a statistically reliable 6th step to the scale for all diagnostic groups. A key previous finding, divergence in task sequencing for children with autism, was confirmed. Comparisons among diagnostic groups, controlling age, and language ability, showed that typical developers mastered the 6 ToM steps ahead of each of the 3 disabled groups, with implications for ToM theories. The final (sarcasm) task challenged even nondisabled 9-year-olds, demonstrating the new scale's sensitivity to post-preschool ToM growth. PMID- 22304466 TI - Dopaminergic modulation of ganglion-cell photoreceptors in rat. AB - A novel class of photoreceptors, the intrinsically photosensitive retinal ganglion cells (ipRGCs), express the photopigment melanopsin and drive non-image forming responses to light such as circadian photoentrainment, the pupillary light reflex and suppression of nocturnal melatonin production in the pineal. Because dendrites from one subclass of these cells - the M1-type ipRGCs - make presumptive synaptic contacts at sites of dopamine release from dopaminergic amacrine cells, they are prime targets for modulation by dopamine, a neuromodulator implicated in retinal circadian rhythms and light adaptation. In patch-clamp recordings from ipRGCs in intact rat retinas, dopamine attenuated the melanopsin-based photocurrent. We confirmed that this was the result of direct action on ipRGCs by replicating the effect in dissociated ipRGCs that were isolated from influences of other retinal neurons. In these recordings, the D1 family dopamine receptor agonist SKF38393 attenuated the photocurrent, caused a modest depolarization, and reduced the input resistance of ipRGCs. The D2-family agonist quinpirole had no effect on the photocurrent. Single-cell reverse transcriptase polymerase chain reaction revealed that the majority of ipRGCs tested expressed drd1a, the gene coding for the D1a dopamine receptor. This finding was supported by immunohistochemical localization of D1a receptor protein in melanopsin-expressing ganglion cells. Finally, the adenylate cyclase activator forskolin, applied in combination with the phosphodiesterase inhibitor IBMX (isobutylmethylxanthine), mimicked the effects of SKF38393 on the ipRGC photocurrent, membrane potential and input resistance, consistent with a D1 receptor signaling pathway. These data suggest that dopamine, acting via D1 family receptors, alters the responses of ipRGCs and thus of non-image-forming vision. PMID- 22304468 TI - Patterning organic/inorganic hybrid Bragg stacks by integrating one-dimensional photonic crystals and macrocavities through photolithography: toward tunable colorful patterns as highly selective sensors. AB - Herein, we report a simple method to fabricate patterned organic/inorganic hybrid 1DPCs by top-down assisted photolithography. Versatile colorful pattern with different size and shape can be produced by selectively exposing the 1DPCs under UV light with predesigned photomask directly. The period change, especially the thickness variation of the top polymer layer, is the main reason for the colorful pattern generation. Because of the swelling property of the polymer layers, the pattern color can be modulated by introducing or taking off organic solvents, leading the as-prepared patterned 1DPCs to be effective sensors with high selectivity. PMID- 22304469 TI - Deep brain stimulation and hemorrhage. PMID- 22304470 TI - Cell death, non-invasively assessed by intrinsic fluorescence intensity of NADH, is a predictive indicator of functional differentiation of embryonic stem cells. AB - BACKGROUND INFORMATION: Continued advances in stem cell biology and stem cell transplantation rely on non-invasive biomarkers to characterise cells and stem cell aggregates. The non-invasive quality of such biomarkers is essential because exogenous labels, probes or reporters can unintentionally and dramatically alter stem cell state as can disruption of cell-cell and cell-matrix interactions. Here, we investigate the utility of the autofluorescent metabolite, nicotinamide adenine dinucleotide (NADH), as a non-invasive, intrinsic biomarker of cell death when detected with multi-photon optical-based approaches. To test this possibility, cell death was induced in murine embryoid bodies (EBs) at an early stage (day 3) of differentiation using staurosporine, an ATP-competitive kinase inhibitor of electron transport. Several hours after staurosporine treatment, EBs were stained with a single-colour, live/dead probe. A single-cross-sectional plane of each EB was imaged to detect the fluorescence intensity of the live/dead probe (extrinsic fluorescence) as well as the fluorescence intensity of NADH (intrinsic fluorescence). EBs were assessed at subsequent time points (days 6-12) for the formation of beating areas as an indicator of functional differentiation. RESULTS: Statistical comparison indicated a strong positive correlation between extrinsic fluorescence intensity of the live/dead stain and intrinsic fluorescence of NADH, suggesting that the intensity of NADH fluorescence could be used to reliably and non-invasively assess death of cells of EBs. Furthermore, EBs that had high levels of cell death soon after aggregate formation had limited ability to give rise to functional cardiomyocytes at later time points. CONCLUSIONS: We demonstrate the utility of NADH fluorescence intensity as a non invasive indicator of cell death in stem cell aggregates when measured using multi-photon excitation. In addition, we show that the degree of stem cell death at early stages of differentiation is predictive for the formation of functional cardiomyocytes. PMID- 22304472 TI - Black hole on film following catheter insertion. AB - Vascular accesses both permanent and temporary play an essential role in the procedure of hemodialysis (HD). The double lumen catheter (DLC) is one form of temporal vascular access which may produce different complications based on where the DLC is inserted. Here, we report a case of a cirrhotic patient receiving HD. The DLC was inserted through the left femoral vein. Later on, an unusual catheter position, mimicking a perforation in the iliac vessel, was noted in the incidental image finding. After venography, we concluded that this DLC had entered the dilated left gonadal vein, and was working well. This condition may be explained by portal hypertension leading to increased frequency of collateral branches and easy dilatation of the left gonadal vein. This condition may develop in a cirrhotic patient with portal hypertension, but there is no harm to a patient. However, this condition leads to an interesting computed tomography image, which may result in misinterpretation of the imaging reports and a clinical misdiagnosis. PMID- 22304473 TI - Hydrogen sulfide in the mammalian cardiovascular system. AB - For more than a century, hydrogen sulfide (H(2)S) has been regarded as a toxic gas. This review surveys the growing recognition of the role of H(2)S as an endogenous signaling molecule in mammals, with emphasis on its physiological and pathological pathways in the cardiovascular system. In biological fluids, H(2)S gas is a weak acid that exists as about 15% H(2)S, 85% HS(-), and a trace of S(2 ). Here, we use "H(2)S" to refer to this mixture. H(2)S has been found to influence heart contractile functions and may serve as a cardioprotectant for treating ischemic heart diseases and heart failure. Alterations of the endogenous H(2)S level have been found in animal models with various pathological conditions such as myocardial ischemia, spontaneous hypertension, and hypoxic pulmonary hypertension. In the vascular system, H(2)S exerts biphasic regulation of a vascular tone with varying effects based on its concentration and in the presence of nitric oxide. Over the past decade, several H(2)S-releasing compounds (NaHS, Na(2)S, GYY4137, etc.) have been utilized to test the effect of exogenous H(2)S under different physiological and pathological situations in vivo and in vitro. H(2)S has been found to promote angiogenesis and to protect against atherosclerosis and hypertension, while excess H(2)S may promote inflammation in septic or hemorrhagic shock. H(2)S-releasing compounds and inhibitors of H(2)S synthesis hold promise in alleviating specific disease conditions. This comprehensive review covers in detail the effects of H(2)S on the cardiovascular system, especially in disease situations, and also the various underlying mechanisms. PMID- 22304474 TI - CP-MLR/PLS directed QSAR study on the glutaminyl cyclase inhibitory activity of imidazoles: rationales to advance the understanding of activity profile. AB - The glutaminyl cyclase inhibitory activity of a series of imidazoles has been analyzed through combinatorial protocol in multiple linear regressions (CP-MLR) and partial least square using different topological and structural descriptors. The QC activity was found to be correlated with 2D-autocorrelation (2DAUTO) and atom centered fragments (ACF) descriptors. The descriptor from 2DAUTO class showed that molecular structure frames of one, six and seven path length associated with atomic van der Waals volumes and polarizability hold scope for modulating QC inhibitory activity. The ACF descriptors suggested that the unsubstituted alkyl fragments and methyl substituted imidazole ring are favorable, while unsaturation in the same and C=N-C=N are unfavorable for activity. The molar refractivity (MR) is conducive for activity. The descriptors identified in the study collectively highlight the significance of molecular volume and polarizability to the QC inhibitory activity of imidazoles. The models are statistically significant and showed good predictivity. PMID- 22304475 TI - (Tosylimino)phenyl-lambda3-iodane as a reagent for the synthesis of methyl carbamates via Hofmann rearrangement of aromatic and aliphatic carboxamides. AB - A new, mild procedure for the Hofmann rearrangement of aromatic and aliphatic carboxamides using (tosylimino)phenyl-lambda(3)-iodane, PhINTs, as a reagent is reported. Because of the mild reaction conditions, this method is particularly useful for the Hofmann rearrangement of substituted benzamides, which usually afford complex reaction mixtures with other hypervalent iodine oxidants. The mild reaction conditions and high selectivity in the reaction of carboxamides with PhINTs allow the isolation of the initially formed labile isocyanates or their subsequent conversion to stable carbamates by treatment with alcohols. PMID- 22304477 TI - Unambiguous characterization of gunshot residue particles using scanning laser ablation and inductively coupled plasma-mass spectrometry. AB - A new method based on scanning laser ablation and inductively coupled plasma-mass spectrometry (LA-ICPMS) for the detection and identification of gunshot residue (GSR) particles from firearms discharges has been developed. Tape lifts were used to collect inorganic residues from skin surfaces. The laser ablation pattern and ICPMS conditions were optimized for the detection of metals present in GSR, such as (121)Sb, (137)Ba, and (208)Pb. Other isotopes ((27)Al, (29)Si, (31)P, (33)S, (35)Cl, (39)K, (44)Ca, (57)Fe, (60)Ni, (63)Cu, (66)Zn, and (118)Sn) were monitored during the ICPMS analyses to obtain additional information to possibly classify the GSR particles as either characteristic of GSR or consistent with GSR. In experiments with real samples, different firearms, calibers, and ammunitions were used. The performed method evaluation confirms that the developed methodology can be used as an alternative to the standard scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) technique, with the significant advantage of drastically reducing the analysis time to less than 66 min. PMID- 22304478 TI - The Escherichia coli cell division protein ZipA forms homodimers prior to association with FtsZ. AB - ZipA is an essential component of the cell division machinery in E. coli and other closely related bacteria. It is an integral membrane protein that binds to FtsZ, tethering it to the inner membrane. ZipA also induces bundling of FtsZ protofilaments and may play a role in regulating FtsA activity; however, the molecular details behind these observations are not clear. In this study we have analyzed the oligomeric state of ZipA in vivo, by chemical cross-linking, and in vitro, by native gel electrophoresis (BN-PAGE). Our data indicate that ZipA can self-associate as a homodimer and that this self-interaction is not dependent on the FtsZ-binding domain. This observation rules out the possibility that FtsZ polymers mediate the ZipA self-interaction. Given this observation, it is possible that a certain population of ZipA is recruited to the division septum in a homodimeric form. PMID- 22304479 TI - Application of proton-transfer-reaction mass spectrometry to the assessment of odorant removal in a biological air cleaner for pig production. AB - There is an urgent need to develop odor reduction technologies for animal production facilities, and this requires a reliable measurement technique for estimating the removal of odorants. The purpose of the present experiment was to investigate the application of proton-transfer-reaction mass spectrometry (PTR MS) for continuous measurements at a biofilter from SKOV A/S installed at a pig production facility. PTR-MS was able to handle the harsh conditions with high humidity and dust load in a biofilter and provide reliable data for the removal of odorants, including the highly odorous sulfur compounds. The biofilter removed 80-99% of carboxylic acids, aldehydes, ketones, phenols, and indoles and ca. 75% of hydrogen sulfide. However, only ~0-15% of methanethiol and dimethyl sulfide was removed. In conclusion, PTR-MS is a promising tool that can be used to improve the development of biological air cleaning and other odor reduction technologies toward significant odorants. PMID- 22304480 TI - Proposal on limits for chemical exposure in saturation divers' working atmosphere: the case of benzene. AB - Saturation diving is performed under extreme environmental conditions. The divers are confined to a limited space for several weeks under high environmental pressure and elevated oxygen partial pressure. At present, divers are protected against chemical exposure by standard exposure limits only adjusted for the increased exposure length, i.e. from 8 to 24 hours a day and from 5 to 7 days a week. The objective of the present study was to indicate a procedure for derivation of occupational exposure limits for saturation diving, termed hyperbaric exposure limits (HEL). Using benzene as an example, a procedure is described that includes identification of the latest key documents, extensive literature search with defined exclusion criteria for the literature retrieved. Hematotoxicity and leukemia were defined as the critical effects, and exposure limits based upon concentration and cumulative exposure data and corresponding risks of leukemia were calculated. Possible interactions of high pressure, elevated pO2, and continuous exposure have been assessed, and incorporated in a final suggestion of a HEL for benzene. The procedure should be applicable for other relevant chemicals in the divers' breathing atmosphere. It is emphasized that the lack of interactions from pressure and oxygen indicated for benzene may be completely different for other chemicals. PMID- 22304481 TI - Theoretical determination of the rate coefficient for the HO2 + HO2 -> H2O2+O2 reaction: adiabatic treatment of anharmonic torsional effects. AB - The HO(2) + HO(2) -> H(2)O(2) + O(2) chemical reaction is studied using statistical rate theory in conjunction with high level ab initio electronic structure calculations. A new theoretical rate coefficient is generated that is appropriate for both high and low temperature regimes. The transition state region for the ground triplet potential energy surface is characterized using the CASPT2/CBS/aug-cc-pVTZ method with 14 active electrons and 10 active orbitals. The reaction is found to proceed through an intermediate complex bound by approximately 9.79 kcal/mol. There is no potential barrier in the entrance channel, although the free energy barrier was determined using a large Monte Carlo sampling of the HO(2) orientations. The inner (tight) transition state lies below the entrance threshold. It is found that this inner transition state exhibits two saddle points corresponding to torsional conformations of the complex. A unified treatment based on vibrational adiabatic theory is presented that permits the reaction to occur on an equal footing for any value of the torsional angle. The quantum tunneling is also reformulated based on this new approach. The rate coefficient obtained is in good agreement with low temperature experimental results but is significantly lower than the results of shock tube experiments for high temperatures. PMID- 22304482 TI - Superlocalization spectral imaging microscopy of a multicolor quantum dot complex. AB - The key factor of realizing super-resolution optical microscopy at the single molecule level is to separately position two adjacent molecules. An opportunity to independently localize target molecules is provided by the intermittency (blinking) in fluorescence of a quantum dot (QD) under the condition that the blinking of each emitter can be recorded and identified. Herein we develop a spectral imaging based color nanoscopy which is capable of determining which QD is blinking in the multicolor QD complex through tracking the first-order spectrum, and thus, the distance at tens of nanometers between two QDs is measured. Three complementary oligonucleotides with lengths of 15, 30, and 45 bp are constructed as calibration rulers. QD585 and QD655 are each linked at one end. The measured average distances are in good agreement with the calculated lengths with a precision of 6 nm, and the intracellular dual-color QDs within a diffraction-limited spot are distinguished. PMID- 22304483 TI - To evaluate the effect of various magnesium stearate polymorphs using powder rheology and thermal analysis. AB - The effects of magnesium stearate (MgSt) polymorphs-anhydrate (MgSt-A), monohydrate (MgSt-M), and dihydrate (MgSt-D)-on rheological properties of powders were evaluated using techniques such as atomic analysis and powder rheometry. Additional evaluation was conducted using thermal analysis, micromeritics, and tableting forces. In this study, binary ratios of neat MgSt polymorphs were employed as lubricants in powder blends containing acetaminophen (APAP), microcrystalline cellulose (MCC), and lactose monohydrate (LAC-M). Powder rheometry was studied using permeability, basic flow energy (BFE), density, and porosity analysis. Thermal conductivity and differential scanning calorimetric analysis of MgSt polymorphs were employed to elucidate MgSt effect on powder blends. The impact of MgSt polymorphs on compaction characteristics were analyzed via tablet compression forces. Finally, the distribution of atomized magnesium (Mg) ions as a function of intensity was evaluated using laser-induced breakdown spectroscopy (LIBS) on tablets. The results from LIBS analysis indicated the dependency of the MgSt polymorphic forms on the atomized Mg ion intensity, with higher Mg ion intensity suggesting higher lubricity index (i.e. greater propensity to over-lubricate). The results from lubricity index suggested the tendency of blends to over-lubricate based on the MgSt polymorphic forms. Finally, tableting forces suggested that MgSt-D and MgSt-A offered processing benefits such as lower ejection and compression forces, and that MgSt-M showed the most stable compression force in single or combined polymorphic ratios. These results suggested that the initial moisture content, crystal arrangement, intra- and inter-molecular packing of the polymorphs defined their effects on the rheology of lubricated powders. PMID- 22304484 TI - Combining the regression discontinuity design and propensity score-based weighting to improve causal inference in program evaluation. AB - The regression discontinuity (RD) design is considered to be the closest to a randomized trial that can be applied in non-experimental settings. The design relies on a cut-off point on a continuous baseline variable to assign individuals to treatment. The individuals just to the right and left of the cut-off are assumed to be exchangeable - as in a randomized trial. Any observed discontinuity in the relationship between the assignment variable and outcome is therefore considered evidence of a treatment effect. In this paper, we describe key advances in the RD design over the past decade and illustrate their implementation using data from a health management intervention. We then introduce the propensity score-based weighting technique as a complement to the RD design to correct for imbalances in baseline characteristics between treated and non-treated groups that may bias RD results. We find that the weighting strategy outperforms standard regression covariate adjustment in the present data. One clear advantage of the weighting technique over regression covariate adjustment is that we can directly inspect the degree to which balance was achieved. Because of its relative simplicity and tremendous utility, the RD design (either alone or combined with propensity score weighting adjustment) should be considered as an alternative approach to evaluate health management program effectiveness when using observational data. PMID- 22304485 TI - Mineralocorticoid receptors mediate cardiac remodelling in morphine-dependent rats. AB - Acute morphine administration decreases cardiac responses to ischaemic injury. This project has determined whether induction of morphine dependence in rats by gradually increasing morphine doses for 21 days induces structural and functional changes in the cardiovascular system because of mineralocorticoid receptor activation, as morphine increases plasma corticosterone concentrations. Morphine dependent rats showed ventricular hypertrophy, increased collagen deposition in the left ventricle together with an increased ventricular stiffness and increased plasma malondialdehyde concentrations without changes in systolic blood pressure or thoracic aortic responsiveness. These parameters were attenuated or normalised in morphine-dependent rats treated with spironolactone (50 mg/kg/day) from days 14-21. These results suggest that morphine dependence induces ventricular remodelling and increased oxidative stress that can be prevented by the mineralocorticoid receptor antagonist, spironolactone. PMID- 22304486 TI - Melatonin prevents hypochlorous acid-induced alterations in microtubule and chromosomal structure in metaphase-II mouse oocytes. AB - Hypochlorous acid (HOCl) is generated by myeloperoxidase, using chloride and hydrogen peroxide as substrates. Here we demonstrate that HOCl alters metaphase II mouse oocyte microtubules and chromosomal (CH) alignment which can be prevented by melatonin. Metaphase-II mouse oocytes, obtained commercially, were grouped as: control, melatonin (150, 200nmol/mL), HOCl (10, 20, 50, and 100nmol/mL), and HOCl (50nmol/mL) pretreated with 150 and 200 nmol/mL of melatonin. Microtubule and CH alignment was studied utilizing an indirect immunofluorescence technique and scored by two observers. Pearson chi-square test and Fisher's exact test were used to compare outcomes between controls and treated groups and also among each group. Poor scores for the spindle and chromosomes increased significantly at 50nmol/mL of HOCl (P<0.001). Oocytes treated with melatonin only at 150 and 200 nmol/mL showed no changes; significant differences (P<0.001) were observed when oocytes exposed to 50nmol/mL of HOCl were compared to oocytes pretreated with 200 nmol/mL melatonin. Fifty percent of the oocytes demonstrated good scores, both in microtubule and CH alterations, when pretreated with melatonin at 150 nmol/mL compared to 0% in the HOCl-only group. HOCl alters the metaphase-II mouse oocyte spindle and CH alignment in a dose-dependant manner, which might be a potential cause of poor oocyte quality (e.g., in patients with endometriosis). Melatonin prevented the HOCl-mediated spindle and CH damage, and therefore, may be an attractive therapeutic option to prevent oocyte damage in endometriosis or inflammatory diseases where HOCl levels are known to be elevated. PMID- 22304487 TI - Charge carrier accumulation in lithium fluoride thin films due to Li-ion absorption by titania (100) subsurface. AB - The thermodynamically required redistribution of ions at given interfaces is being paid increased attention. The present investigation of the contact LiF/TiO(2) offers a highly worthwhile example, as the redistribution processes can be predicted and verified. It consists in Li ion transfer from LiF into the space charge zones of TiO(2). We not only can measure the resulting increase of lithium vacancy conductivity in LiF, we also observe a transition from n- to p type conductivity in TiO(2) in consistency with the generalized space charge model. PMID- 22304488 TI - JAK2 V617F mutation prevalence in myeloproliferative neoplasms in Pernambuco, Brazil. AB - BACKGROUND: The JAK2 V617F mutation is associated with three myeloproliferative neoplasms (MPNs): polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). It generates an unregulated clonal hematopoietic progenitor and leads to abnormal increased proliferation of one or more myeloid lineages. Subjects bearing this mutation may present more frequently with complications such as thrombosis and bleeding, and no specific treatment has yet been developed for BCR-ABL-negative JAK2 V617F-negative MPNs. AIMS: To determine the prevalence of JAK2 V617F in MPNs in Pernambuco, Brazil, and to compare it with previous studies. MATERIAL AND METHODS: 144 blood samples were collected at the Hospital of Hematology of the HEMOPE Foundation and were genotyped by polymerase chain reaction-restriction fragment length polymorphism with BsaXI enzymatic digestion. RESULTS AND DISCUSSION: 88% (46/52) of the patients with PV, 47% (39/81) with ET, and 77% (8/11) with PMF were positive for JAK2 V617F, while more than 35% of the individuals were JAK2 V617F-negative, confirming a high prevalence of this abnormality in MPNs, more frequently with a low mutated allele burden, similar to what has been reported in other Western countries, despite differences among methods used to detect this mutation. Screening for JAK2 V617F may allow specific management of these diseases with JAK2 inhibitors in the future and highlights the need for further studies on the pathogenesis of BCR-ABL negative JAK2 V617F-negative MPNs. PMID- 22304489 TI - Scalp cooling for hair preservation and associated characteristics in 1411 chemotherapy patients - results of the Dutch Scalp Cooling Registry. AB - BACKGROUND: Chemotherapy-induced alopecia is a frequently occurring side effect of cancer treatment with a high psychological impact which can be prevented by scalp cooling. With this multi-centre patient series we estimated the results of scalp cooling for currently used chemotherapies to provide patient information and we identified characteristics associated with the results. MATERIAL AND METHODS: The Dutch Scalp Cooling Registry collected data on scalp-cooled patients in 28 Dutch hospitals. Nurses and patients completed questionnaires on patients, chemotherapy and scalp cooling characteristics. Logistic regression analysis was used to examine associated characteristics of the scalp cooling result. RESULTS: Overall, 50% of the 1411 scalp-cooled patients did not wear a head cover during their last chemotherapy session. Patients were satisfied with the results in 8% of cases after TAC chemotherapy and up to 95% after paclitaxel treatment. Besides type of chemotherapy, higher dose and shorter infusion time, older age, female gender and non-West-European type of hair significantly increased the proportion head cover use. Hair length, quantity, chemical manipulation (dyeing, waving, colouring), wetting hair before scalp cooling, and treatment with chemotherapy ever before did not influence the degree of head covering among patients. CONCLUSIONS: Scalp cooling results as recorded in this open patient registry were positive for most regimens, justifying it's use by all eligible patients, except for those needing TAC. Lengthening infusion time may improve the results. PMID- 22304490 TI - Dosimetric impact of a frame-based strategy in stereotactic radiotherapy of lung tumors. AB - INTRODUCTION: Technological innovations have taken stereotactic body radiotherapy (SBRT) from frame-based strategies to image-guided strategies. In this study, cone beam computed tomography (CBCT) images acquired prior to SBRT of patients with lung tumors was used to study the dosimetric impact of a pure frame-based strategy. MATERIAL AND METHODS: Thirty patients with inoperable lung tumors were retrospectively analyzed. All patients had received CBCT-guided SBRT with 3 fractions of 15 Gy to the planning target volume (PTV) margin including immobilization in a stereotactic body frame (SBF). Using the set-up corrections from the co-registration of the CBCT with the planning CT, all individual dose plans were recalculated with an isocenter position equal to the initial set-up position. Dose Volume Histogram (DVH) parameters of the recalculated dose plans were then analyzed. RESULTS: The simulated plans showed that 88% of all fractions resulted in minimum 14.5 Gy to the internal target volume (ITV). For the simulated summed treatment (3 fractions per patient), 83% of the patients would minimum receive the prescription dose (45 Gy) to 100% of the ITV and all except one would receive the prescription dose to more than 90% of the ITV. CONCLUSIONS: SBRT including SBF, but without image guidance, results in appropriate dose coverage in most cases, using the current margins. With image guidance, margins for SBRT of lung tumors could possibly be reduced. PMID- 22304491 TI - Caregiver burden among nocturnal home hemodialysis patients. AB - Recent studies have suggested improvements in quality of life (QOL) in patients on quotidian dialysis compared with conventional hemodialysis. Few studies have focused on the burden and QOL in caregivers of patients with end-stage renal disease (ESRD) on nocturnal home hemodialysis (NHD). We aim to assess the caregivers' burden, QOL, and depressive symptoms and to compare these parameters with their patients' counterparts. Cross-sectional surveys were sent to 61 prevalent NHD patients and their caregivers. Surveys assessed demographics, general self-perceived health using the 12-Item Short Form Health Survey (SF-12) and the presence of depression using the Beck Depression Inventory. Subjective burden on caregivers was assessed by the Caregiver Burden scale and was compared with perceived burden by the patients. Thirty-six patients and 31 caregivers completed the survey. The majority of caregivers were female (66%), spouse (81%) with no comorbid illness (72%). Their mean age was 51 +/- 11 years. Patients were mostly male (64%) with a median ESRD vintage of 60 months (interquartile range [IQR], 18-136 months) and a mean age of 52 +/- 10 years. Compared to caregivers, patients had lower perceived physical health score but had similar mental health score. Depression criteria were present in 47% of patients and 25% of caregivers. Total global burden perceived by either caregivers or patients is relatively low. Although there is a relatively low global burden perceived by caregivers and patients undergoing NHD, a significant proportion of both groups fulfilled criteria for depression. Further innovative approaches are needed to support caregivers and patients performing NHD to reduce the intrusion of caring for a chronic illness and the risk of developing depression. PMID- 22304492 TI - Enhanced molecular order in polythiophene films electropolymerized in a mixed electrolyte of anionic surfactants and boron trifluoride diethyl etherate. AB - We synthesized polythiophene (PTh) films on stainless steel electrodes using chronoamperometry in boron trifluoride diethyl etherate (BFEE) electrolyte with anionic surfactants. The presence of the anionic surfactants in BFEE reduced the oxidation potential of thiophene and increased the oxidation current during electropolymerization. The measured in-plane electrical conductivity of PTh films synthesized in the presence of anionic surfactants was up to 300% higher than that of films synthesized under similar conditions without surfactants. The observed increase in conductivity reflects the improved order and packing of polymer chains revealed by X-ray diffraction. PMID- 22304493 TI - Prevalence and correlates of sexual risk among male and female sex workers in Tijuana, Mexico. AB - We investigated prevalence and correlates of sexual risk behaviours among male and female sex workers in Tijuana, Mexico, the busiest border crossing area on the US - Mexico border, analysing survey data from a purposive, cross-sectional sample of male and female sex workers who worked in a range of indoor and outdoor settings. Logistic regression was used to determine factors that were associated with sexual risk-taking, defined as failing to use a condom with last client. In bivariate regression models, gender, work setting (e.g., indoor vs. outdoor), poverty, engaging in survival sex, marital status and perceived drug addiction were correlated with sexual risk. When controlling for work location, housing insecurity, poverty, survival sex, marital status and perceived drug addiction, male sex workers were still 10 times more likely than female sex workers (FSW) to engage in sex without a condom during their last encounter with a client. And, although FSW were significantly more likely than males to have used a condom with a client, they were significantly less likely than males to have used a condom with their regular partner. Future research should further examine how gender shapes sexual risk activities in both commercial and non-commercial relationships. PMID- 22304494 TI - Microencapsulation effectiveness of small active molecules in biopolymer by ultrasonic atomization technique. AB - A method to produce biopolymeric (alginate) microparticles by ultrasonic assisted atomization, previously developed, has been applied to the production of microparticles loaded with a small active molecule (theophylline). Fine loaded alginate droplets have been cross-linked with divalent ions to produce microparticles. Once produced, the particles have been separated by centrifugation or filtration and then they have been dried. Drug release has been evaluated by dissolution tests, dissolving the dried particles in acidic solution at pH 1 for a given time and then at pH 7 to simulate the stomach and intestinal environment, respectively. The encapsulation efficiency and the drug loading have been investigated and the operating conditions have been changed to clarify the role of the transport phenomena on the overall process. To increase the drug loading, shorter separation time and better network's structure were identified as the key operating parameters to allow the process to gain interest from a practical point of view. PMID- 22304495 TI - Impact of tautomery of 3-(4H-1,2,4-triazol-3-ylthio)-N-phenylpropanamide on the COX-1 inhibitory mechanism. AB - Earlier, we have reported the synthesis and anti-inflammatory evaluation of different 3-(4H-1,2,4-triazol-3-ylthio)-N-substituted propanamide. In this article, we are reporting the various tautomeric forms of the most active anti inflammatory compound, 3-(4H-1,2,4-triazol-3-ylthio)-N-phenylpropanamide (6a) and their virtual screening by molecular docking using six principle tautomeric forms. Docking analysis suggested that compound 3-(4H-1,2,4-triazol-3-ylthio)-N phenylpropanamide (6a) bound with COX-1 selectively and drug receptor complex was stabilized by tautomerism. Noticeably, hydroxy group formed by tautomerism appreciably improve the drug receptor interactions. It was also supervised that the compound 3-(4H-1,2,4-triazol-3-ylthio)-N-phenylpropanamide (6a) docked near the gate of COX-1 active site and might block the conversion of arachidonic acid to prostaglandin (PG) H2 in the active site of COXs. Moreover, we have carried out receptor based electrostatic analysis to clarify the electronic, steric and hydrophobic field requirement of 3-(4H-1,2,4-triazol-3-ylthio)-N phenylpropanamide (6a) to interact with COX -1 receptor. PMID- 22304496 TI - Safety of prophylactic intracameral moxifloxacin use in cataract surgery. AB - PURPOSE: To evaluate posterior and anterior segment safety of an intracameral injection of moxifloxacin as prophylaxis for endophthalmitis in cataract surgery. METHODS: In this study, 60 eyes of 60 patients were included. In the first group, only 5% povidine iodine drop was administrated to 30 patients at the end of the surgery, while 30 patients were treated with intracameral moxifloxacin (250 MUg/0.050 mL) additionally in the second group. Visual acuity, intraocular pressure, corneal pachymetry, corneal clarity, and edema and retinal thickness were evaluated preoperatively and for day 3 postoperatively for each group and were compared. RESULTS: Mean preoperative visual acuity was 0.7 +/- 0.9 LogMAR in both groups 1 and 2, while mean postoperative visual acuity was 0.05 +/- 1.00 LogMAR in both groups. Preoperative and postoperative intraocular pressure averaged 13.2 +/- 2.0 and 13.2 +/- 2.1 mmHg, respectively, in the first group, while preoperative and postoperative intraocular pressure was 14.9 +/- 2.1 and 14.3 +/- 2.0, respectively, in the second group. Preoperative and postoperative visual acuity changes and intraocular pressure changes were not significantly different between 2 groups. There was no single case of corneal edema. In the first group, preoperative pachymetry was 523 +/- 44 and postoperative pachmetry was 536 +/- 45 MUm, while in the second group preoperative pachymetry was 527 +/- 43 and postoperative pachymetry was 543 +/- 42 MUm. Preoperative and postoperative pachymetry changes were not significantly different between 2 groups. Mean preoperative macular thickness in the first group was 188 +/- 7.73 MUm, while it was measured as 189 +/- 7.75 MUm postoperatively. In the second group, mean preoperative macular thickness was 188 +/- 8.89 MUm, while it was 189 +/- 9.61 MUm postoperatively. Preoperative and postoperative optical coherence tomography (OCT) measure changes were not significantly different between the 2 groups. No study-related adverse events were noted. CONCLUSION: There was no increased safety risk associated with a 250 MUm/0.050 mL intracameral injection of moxifloxacin, which appears to be safe in the prophylaxis of endophthalmitis after cataract surgery. PMID- 22304497 TI - Retina expression and cross-species validation of gene silencing by PF-655, a small interfering RNA against RTP801 for the treatment of ocular disease. AB - PURPOSE: PF-655, a synthetic 19-mer siRNA, targeting the RTP801 gene is currently in clinical trials for the treatment of wet age-related macular degeneration and diabetic macular edema. Preclinical studies have shown a dose-related suppression of RTP801 expression in rat disease models. Investigative studies were conducted with PF-655 to validate the Dutch-Belted rabbit as a biologically relevant species for gene silencing to support nonclinical ocular toxicity and continual dosing studies. METHODS: Cross-species comparison and DNA sequencing was done to determine the level of homology between PF-655 and rabbit RTP801. Human (HEK 293) and rabbit (SIRC cornea) cell lines were stimulated with CoCl(2) to mimic hypoxic stress (an inducer of RTP801 expression) and treated with PF-655. Taqman polymerase chain reaction and immunoblot analysis were performed to gauge RTP801 expression in cell culture and rabbit retinas. RESULTS: Sequence analysis showed a 1-base mismatch in the PF-655 targeting site from genomic DNA of Dutch-Belted rabbit and the SIRC cell line, a cornea cell derived from the New Zealand White rabbit. HEK and SIRC CoCl(2)-stressed cells induced RTP801 expression 10-20-fold above control conditions. Treatment with 20 or 100 nM PF-655 showed a decrease in gene expression, 40%-50% relative to appropriate controls. RTP801 mRNA was detectable in primary rabbit retina tissues, with cycle threshold values showing a large linear range for the assay. CONCLUSION: These results support our investigation into cross-species validation of gene suppression by a therapeutic siRNA designed to a human gene. The SIRC cell line was utilized as a surrogate to test the degree of RTP801 gene silencing induced by PF-655 in vitro. With a 1 base mismatch, the level of silencing in a rabbit ocular cell line was comparable to that of a human cell line. Sequence analysis and expression data confirmed the relevance of the RTP801 target gene in rabbits and the utility of this species as a relevant animal model. Additionally, our work outlines a tractable method that validates relevant larger non-rodent species for ophthalmic drug testing. PMID- 22304499 TI - Amsacrine as a topoisomerase II poison: importance of drug-DNA interactions. AB - Amsacrine (m-AMSA) is an anticancer agent that displays activity against refractory acute leukemias as well as Hodgkin's and non-Hodgkin's lymphomas. The drug is comprised of an intercalative acridine moiety coupled to a 4'-amino methanesulfon-m-anisidide headgroup. m-AMSA is historically significant in that it was the first drug demonstrated to function as a topoisomerase II poison. Although m-AMSA was designed as a DNA binding agent, the ability to intercalate does not appear to be the sole determinant of drug activity. Therefore, to more fully analyze structure-function relationships and the role of DNA binding in the action of m-AMSA, we analyzed a series of derivatives for the ability to enhance DNA cleavage mediated by human topoisomerase IIalpha and topoisomerase IIbeta and to intercalate DNA. Results indicate that the 3'-methoxy (m-AMSA) positively affects drug function, potentially by restricting the rotation of the headgroup in a favorable orientation. Shifting the methoxy to the 2'-position (o-AMSA), which abrogates drug function, appears to increase the degree of rotational freedom of the headgroup and may impair interactions of the 1'-substituent or other portions of the headgroup within the ternary complex. Finally, the nonintercalative m-AMSA headgroup enhanced enzyme-mediated DNA cleavage when it was detached from the acridine moiety, albeit with 100-fold lower affinity. Taken together, our results suggest that much of the activity and specificity of m-AMSA as a topoisomerase II poison is embodied in the headgroup, while DNA intercalation is used primarily to increase the affinity of m-AMSA for the topoisomerase II-DNA cleavage complex. PMID- 22304502 TI - Abstracts of the 17th Annual Fall Scientific Meeting of the Sexual Medicine Society of North America. Las Vegas, Nevada, USA. November 10-13 2011. PMID- 22304504 TI - Interactions of odorants with olfactory receptors and receptor neurons match the perceptual dynamics observed for woody and fruity odorant mixtures. AB - The present study aimed to create a direct bridge between observations on peripheral and central responses to odorant mixtures and their components. Three experiments were performed using mixtures of fruity (isoamyl acetate; ISO) and woody (whiskey lactone; WL) odorants known to contribute to some of the major notes in Burgundy red wine. These experiments consisted of (i) calcium imaging of human embryonic kidney cells (HEK293T) transfected with olfactory receptors (ORs); (ii) single-unit electrophysiological recordings from olfactory receptor neurons (ORNs) and analyses of electro-olfactogram (EOG) responses in the rat nose in vivo; and (iii) psychophysical measurements of the perceived intensity of the mixtures as rated by human subjects. The calcium imaging and electrophysiological results revealed that ISO and WL can act simultaneously on single ORs or ORNs and confirm that receptor responses to mixtures are not the result of a simple sum of the effects of the individual mixture compounds. The addition of WL to ISO principally suppressed the ORN activation induced by ISO alone and was found to enhance this activation in a subset of cases. In the human studies, the addition of high concentrations of WL to ISO decreased the perceived intensity of the ISO. In contrast, the addition of low concentrations of WL enhanced the perceived intensity of the fruity note (ISO) in this mixture, as it enhanced EOG responses in ORNs. Thus, both OR and ORN responses to ISO + WL mixtures faithfully reflected perceptual response changes, so the odour mixture information is set up after the peripheral stage of the olfactory system. PMID- 22304506 TI - Seeking better health care outcomes: the ethics of using the "nudge". AB - Policymakers, employers, insurance companies, researchers, and health care providers have developed an increasing interest in using principles from behavioral economics and psychology to persuade people to change their health related behaviors, lifestyles, and habits. In this article, we examine how principles from behavioral economics and psychology are being used to nudge people (the public, patients, or health care providers) toward particular decisions or behaviors related to health or health care, and we identify the ethically relevant dimensions that should be considered for the utilization of each principle. PMID- 22304507 TI - What counts as a nudge? PMID- 22304503 TI - Glutathione redox control of asthma: from molecular mechanisms to therapeutic opportunities. AB - Asthma is a chronic inflammatory disorder of the airways associated with airway hyper-responsiveness and airflow limitation in response to specific triggers. Whereas inflammation is important for tissue regeneration and wound healing, the profound and sustained inflammatory response associated with asthma may result in airway remodeling that involves smooth muscle hypertrophy, epithelial goblet-cell hyperplasia, and permanent deposition of airway extracellular matrix proteins. Although the specific mechanisms responsible for asthma are still being unraveled, free radicals such as reactive oxygen species and reactive nitrogen species are important mediators of airway tissue damage that are increased in subjects with asthma. There is also a growing body of literature implicating disturbances in oxidation/reduction (redox) reactions and impaired antioxidant defenses as a risk factor for asthma development and asthma severity. Ultimately, these redox-related perturbations result in a vicious cycle of airway inflammation and injury that is not always amenable to current asthma therapy, particularly in cases of severe asthma. This review will discuss disruptions of redox signaling and control in asthma with a focus on the thiol, glutathione, and reduced (thiol) form (GSH). First, GSH synthesis, GSH distribution, and GSH function and homeostasis are discussed. We then review the literature related to GSH redox balance in health and asthma, with an emphasis on human studies. Finally, therapeutic opportunities to restore the GSH redox balance in subjects with asthma are discussed. PMID- 22304508 TI - Avoiding selective ethical objections to nudges. PMID- 22304509 TI - What does not budge for any nudge? PMID- 22304510 TI - Nudges in public health: paternalism is paramount. PMID- 22304511 TI - Don't call me "nudge": the ethical obligation to use effective interventions to promote public health. PMID- 22304512 TI - Value-ladenness and rationality in health communication. PMID- 22304513 TI - Nudge ethics: just a game of billiards? PMID- 22304514 TI - Nudge ethics for health plans. PMID- 22304515 TI - Redefining the clinical relationship in the era of incentives. PMID- 22304516 TI - Reconciling bioethics with health care strategies born of behavioral economics and psychology. PMID- 22304517 TI - Balancing autonomy and decisional enhancement: an evidence-based approach. PMID- 22304518 TI - Nudge, nudge or shove, shove-the right way for nudges to increase the supply of donated cadaver organs. AB - Richard Thaler and Cass Sunstein (2008) contend that mandated choice is the most practical nudge for increasing organ donation. We argue that they are wrong, and their mistake results from failing to appreciate how perceptions of meaning can influence people's responses to nudges. We favor a policy of default to donation that is subject to immediate family veto power, includes options for people to opt out (and be educated on how to do so), and emphasizes the role of organ procurement organizations and in-house transplant donation coordinators creating better environments for increasing the supply of organs and tissues obtained from cadavers. This policy will provide better opportunities for offering nudges in contexts where in-house coordinators work with families. We conclude by arguing that nudges can be introduced ethically and effectively into these contexts only if nudge designers collaborate with in-house coordinators and stakeholders. PMID- 22304519 TI - When a nudge becomes a shove. PMID- 22304520 TI - When does a nudge become a shove in seeking consent for organ donation? PMID- 22304521 TI - Lack of political will and public trust dooms presumed consent. PMID- 22304522 TI - Should we be "nudging" for cadaveric organ donations? PMID- 22304524 TI - HPLC/ICP-MS in combination with "reverse" online isotope dilution in drug metabolism studies. AB - During the development of a new drug compound, its metabolism needs to be unraveled. For quantification of the metabolites formed, the drug under investigation is traditionally synthesized with a radiolabel ((14)C or (3)H) and the metabolites present in different matrixes (blood, urine, feces) upon drug administration are determined by means of high-performance liquid chromatography (HPLC) coupled to radiodetection. This approach allows for quantification of the metabolites formed and enables a straightforward distinction between exogenous (i.e., drug-related) and endogenous species (as only the radiolabeled species are detected). However, in some cases, the use of a radiolabeled compound in human in vivo studies is not advisible, e.g., for drug compounds or their metabolites showing a long plasma or tissue half-life. In cases where the candidate drug molecule contains an element detectable by means of inductively coupled plasma mass spectrometry (ICP-MS), HPLC/ICP-MS is a promising alternative approach. However, the method lacks specificity when a distinction between drug-related species and endogenous compounds containing the same target element needs to be accomplished. As a result, we have developed an HPLC/ICP-MS-based method combined with "reverse" online isotope dilution ("reverse" online ID) for metabolite quantification. The methodology was evaluated by the analysis of feces samples from rats dosed with a (81)Br-labeled drug compound. The method allows for both (i) valid quantification of the drug metabolites and (ii) distinction among endogenous, exogenous, and "mixed" species, based on their isotopic "fingerprint". A good repeatability (relative standard deviation of 4.2%) and limit of detection (0.35 mg of drug compound L(-1) of feces extract), of the same order of magnitude as those observed for "normal" online ID HPLC/ICP-MS and HPLC/radiodetection, were achieved. PMID- 22304525 TI - Solvent-free acid-catalyzed ring-opening of epoxidized oleochemicals using stearates/stearic acid, and its applications. AB - Toxic solvent and strong acid catalysts causing environmental issues have been mainly used for ring-opening of epoxidized oleochemicals. Here, we demonstrated that magnesium stearate (Mg-stearate) was a high efficient catalyst for solvent free ring-opening of epoxidized methyl oleate, a model compound of midchain epoxide. Mg-stearate resulted in the highest yield (95%) and conversion rate (99%) toward midchain alkoxyesters under the same conditions (160 degrees C, 12 h) superior to other fatty acid derivatives such as a Lewis acid (lithium and sodium stearate) and Bronsted acid (stearic acid). Based on this chemical study, we synthesized biogrease and thermoplastic using epoxidized soybean oil (ESO) and Mg-stearate via one-pot, solvent-free, and purification-free process. Mg-stearate played a significant role as a reactant for epoxide ring-opening and as a thickener when excess loading rate was used; viscosity increased from 1800 to 4500 Pa.s at 25 degrees C when ESO:Mg-stearate increased from 1:1 equiv to 1:2, then behaved like thermoplastics (T(g) = -27 degrees C, T(m) = 90 degrees C) with 1:4. PMID- 22304526 TI - Longitudinal links between spanking and children's externalizing behaviors in a national sample of White, Black, Hispanic, and Asian American families. AB - This study examined whether the longitudinal links between mothers' use of spanking and children's externalizing behaviors are moderated by family race/ethnicity, as would be predicted by cultural normativeness theory, once mean differences in frequency of use are controlled. A nationally representative sample of White, Black, Hispanic, and Asian American families (n = 11,044) was used to test a cross-lagged path model from 5 to 8 years old. While race/ethnic differences were observed in the frequency of spanking, no differences were found in the associations of spanking and externalizing over time: Early spanking predicted increases in children's externalizing while early child externalizing elicited more spanking over time across all race/ethnic groups. PMID- 22304527 TI - Synthesis of 8-aryl-substituted coumarins based on ring-closing metathesis and Suzuki-Miyaura coupling: synthesis of a furyl coumarin natural product from Galipea panamensis. AB - The synthesis of 7-methoxy-8-(4-methyl-3-furyl)-2H-chromen-2-one, a natural product with antileishmanial activity recently isolated from the plant Galipea panamensis, is described. The key step is a Suzuki-Miyaura coupling of a furan-3 boronic acid and an 8-halocoumarin, which is advantageously synthesized using a ring-closing metathesis reaction. Several non-natural analogues are also available along these lines. PMID- 22304528 TI - Melatonin activates the Nrf2-ARE pathway when it protects against early brain injury in a subarachnoid hemorrhage model. AB - Melatonin has beneficial effects against early brain injury (EBI) by modulating cerebral oxidative stress after experimental subarachnoid hemorrhage (SAH); however, few investigations relate to the precise underlying molecular mechanisms. To date, the relation between melatonin and nuclear factor erythroid 2-related factor 2 and antioxidant responsive element (Nrf2-ARE) pathway has not been studied in SAH models. This study was undertaken to evaluate the influence of melatonin on Nrf2-ARE pathway in rats after SAH. Adult male SD rats were divided into four groups: (i) control group (n=18); (ii) SAH group (n=18); (iii) SAH+vehicle group (n=18); and (iv) SAH+melatonin group (n=18). The rat SAH model was induced by injection of 0.3mL fresh arterial, nonheparinized blood into the prechiasmatic cistern in 20s. In SAH+melatonin group, melatonin was administered i.p. at 150mg/kg at 2 and 24hr after the induction of SAH. Brain samples were extracted at 48hr after SAH. Treatment with melatonin markedly increased the expressions of Nrf2-ARE pathway-related agents, such as Nrf2, heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1, and glutathione S-transferase alpha-1. Administration of melatonin following SAH significantly ameliorated EBI, including brain edema, blood-brain barrier (BBB) impairment, cortical apoptosis, and neurological deficits. In conclusion, post-SAH melatonin administration may attenuate EBI in this SAH model, possibly through activating Nrf2-ARE pathway and modulating cerebral oxidative stress by inducing antioxidant and detoxifying enzymes. PMID- 22304529 TI - Attentional bias to violent images in survivors of dating violence. AB - This study investigated the time-course characteristics of attentional bias, such as vigilance and maintenance, towards violent stimuli in dating violence (DV) survivors. DV survivors with PTSD symptoms (DV-PTSD group; n=14), DV survivors without PTSD symptoms (Trauma Control group; n=14), and individuals who were never exposed to dating violence (NDV group; n=15) viewed slides that presented four categories of images (violent, dysphoric, positive, and neutral) per slide, for ten seconds. Our results revealed that the DV-PTSD group spent more time on violent stimuli than did the Trauma Control or NDV groups. The DV survivors, both with and without PTSD symptoms, spent more time on dysphoric stimuli and less time on happy stimuli than did the NDV group. In addition to the effects of PTSD, researchers should also be considering the effects of simple traumatic exposure. PMID- 22304530 TI - Managing asthma in primary care through imperative outcomes. AB - RATIONALE, AIMS AND OBJECTIVES: To evaluate asthma management and control in primary care clinics so as to design improvements based on guideline-directed outcomes. METHODS: In this study, all medical records of asthma-diagnosed patients (children as well as adults, entire lifespan, asthma-related visits or not) were retrospectively reviewed as a basis for assessing the level of guideline adherence and asthma control. Six primary health care clinics were visited in the Dr Kenneth Kaunda Municipal District, Potchefstroom, South Africa during May to July 2008, 2009 and 2010. RESULTS: A total of 323 asthma patient records were reviewed over the three time slots, resulting in 125, 87, and 111 patients respectively. A suboptimal clinical asthma control picture, with a mere 16% (n = 20) of females and 2% (n = 3) of males with Peak Expiratory Flow (PEF) percentages above 60%, were observed in the initial assessment. Improvement in control was observed during the following time slot, but with an end result in 2010 of no PEF percentages above 60% for males and only 9% (n = 7) for females. CONCLUSION: Over all three of the data collection periods adherence to effectively applied management of asthma guidelines proved to be below the minimum recommended clinical evaluation work-up as set out by the Expert Panel Report 3 (EPR3) of the National Asthma Education and Prevention Program (NAEPP). Applying a greater focus on essential outcomes through different disease management documents resulted in an improved quality of managed care, but still requires dedicated and continuous education and motivation. (NWU-0052-08-A5). PMID- 22304531 TI - Induction of chirality in an achiral monolayer at the liquid/solid interface by a supramolecular chiral auxiliary. AB - An achiral oligo(p-phenylene vinylene) derivative with a ureido-triazine hydrogen bonding unit self-assembles into rows of hydrogen bonded dimers at the liquid/solid interface. Scanning tunneling microscopy reveals the formation of chiral domains, but overall, the surface remains racemic. Addition of a chiral auxiliary which is able to interact with the dimers through hydrogen bonding, showed that global organizational chirality could be achieved since a majority of the domains show the same handedness. After removing the chiral auxiliary with a volatile solvent, the global organizational chirality could be trapped, revealing a memory effect. With this straightforward supramolecular approach, we were able to create a chiral surface with preferred handedness composed of achiral molecules at the air/solid interface. PMID- 22304533 TI - Important areas of the central binocular visual field for daily functioning in the visually impaired. AB - PURPOSE: To determine the areas of the central binocular visual field which correspond best with self-reported vision related activity limitations (VRAL) in individuals with visual impairment using a clinically relevant and accessible technique. METHODS: One hundred participants with mixed visual impairment undertook binocular threshold visual field testing using a Humphrey 30-2 SITA Fast program. The Activity Inventory (AI) was administered to assess overall, mobility related and reading related self-reported VRAL as part of a face-to-face clinical interview. Different eccentricities of the binocular field (central 5, 5 10, and 10-30 degrees ) were compared to self-reported VRAL in bivariate analyses and further explored using multivariate analyses. RESULTS: All areas of the binocular visual field were significantly associated with self-reported VRAL in bivariate analyses, with greater field loss associated with increased VRAL (p < 0.001). Multivariate analyses identified that function of the central 5-10 degrees best predicted overall self-reported VRAL, and function of the central 5 degrees (especially the right-hand-side) and the central 10-30 degrees (especially 10-20 degrees ) best predicted self-reported VRAL in reading and mobility tasks, respectively. CONCLUSIONS: The results highlight the association between central binocular visual fields and self-reported VRAL in people with visual impairment. Central binocular fields can be measured using a widely available threshold test in order to understand the likely functional limitations of those with vision loss, particularly in mobility tasks. Self-reported VRAL can be estimated using the regression equations and graphs provided and difficulty levels in specific tasks can be determined. PMID- 22304534 TI - Proinflammatory cytokines and complement activation in salvaged blood from abdominal aortic aneurism surgery and total hip replacement surgery. AB - BACKGROUND: Levels of proinflammatory mediators in unwashed salvaged blood from abdominal aortic aneurism (AAA) surgery are unknown. We hypothesized that there are higher levels of these mediators in unwashed blood salvaged in AAA surgery compared to hip replacement surgery. STUDY DESIGN AND METHODS: Ten patients scheduled for AAA surgery (Group A) and 10 patients for total hip replacement surgery (Group H) were included. Blood samples from the autotransfusion set were obtained during surgery and arterial samples before, during, and 6 hours after surgery. Determination of interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha, activated complement 3 (C3a), and high-sensitivity C-reactive protein (CRP) were performed. Salvaged blood was not retransfused. RESULTS: Levels (median [range]) of IL-8 in blood in the salvage system were higher in Group A versus Group H (215.3 [22.5-697.2] vs. 35.3 [16.7-66.6] pg/mL; p = 0.002). Higher levels of IL-6 were also seen in Group A versus Group H (60.0 [52.6-62.2] vs. 42.34 [19.4-62.2] pg/mL; p = 0.049). Levels of IL-6 in blood sampled during surgery were approximately fivefold higher in Group A versus Group H (p = 0.023), whereas approximately 70% higher levels of C3a were observed in Group H versus Group A (p = 0.021). Postoperative concentrations of IL-1beta (p = 0.002), IL-6 (p = 0.001), and IL-8 (0.005) were higher in Group A versus Group H. CONCLUSION: Salvaged blood in AAA surgery contains substantially higher levels of proinflammatory mediators compared to blood in total hip replacement surgery. PMID- 22304535 TI - Synthesis of (+)-patulolide C via an asymmetric hydroformylation/macrocyclization cascade. AB - A highly atom-economical total synthesis of (+)-patulolide C has been accomplished in three steps from the known (2R)-8-nonyn-2-ol in 49% overall yield and 93% de. A Rh(I)-catalyzed asymmetric hydroformylation (AHF)/ intramolecular Wittig olefination cascade was utilized to set the C4-hydroxyl stereochemistry and E-olefin geometry as well as form the macrolactone. PMID- 22304536 TI - Necrotizing fasciitis of thigh associated with Escherichia coli bacteremia in a patient on chronic hemodialysis. AB - Necrotizing fasciitis is a lethal soft tissue infection for its rapid progression to septic shock. We present a 59-year-old male on chronic hemodialysis (HD). We made the diagnosis of necrotizing fasciitis of the right thigh due to the crepitus from physical examination and subcutaneous emphysema from an X film. He was successfully treated with antibiotics and surgical debridement. The blood and surgical drainage cultures showed Escherichia coli, which is less commonly seen in cutaneous infection. The colonoscopic finding revealed adenomatous polyps. Necrotizing fasciitis in patients on HD requires early diagnosis and aggressive treatment to ensure the favorable clinical outcomes. PMID- 22304537 TI - Frequencies of CYP3A5*1/*3 variants in a Moroccan population and effect on tacrolimus daily dose requirements in renal transplant patients. AB - The cytochromes P450 are a superfamily of oxidative enzymes, which are implicated in the metabolism of a large number of endogenous substances as well as exogenous chemicals. The cytochrome P450 (CYP3A5) appears to play an important role in drug metabolism activity. The most frequent mutation in the CYP3A5 gene, affecting its activity, consists of a G6986A transition within intron 3. In this study, we determined the allelic frequency of CYP3A5*3 in a Moroccan population, consisting of 108 individuals including 10 renal transplant patients. About 8.33% (9/108) of the subjects were homozygous wild-type (CYP3A5*1/*1), 37.04% (40/108) were heterozygous (CYP3A5*1/*3), and 54.63% (59/108) were homozygous (CYP3A5*3/*3). Therefore, CYP3A5*3 variant was the most frequent allele detected at 73.15%. In the second part of this work, we assessed the influence of the CYP3A5 polymorphism on tacrolimus doses required for 10 renal transplant patients who are receiving tacrolimus as immunosuppressive therapy. Our results showed that, during the first 3 months after kidney transplantation, the tacrolimus daily requirements for heterozygous patients (CYP3A5*3/*1) were higher compared with homozygous patients (CYP3A5*3/*3) (0.133 +/- 0.026 vs. 0.21 +/- 0.037 mg/kg/day). After the third month the difference was also observed, whereby the mean of tacrolimus daily requirements for patients with CYP3A5*3/*3 and CYP3A5*1/*3 was 0.053 +/- 0.013 and 0.08 +/- 0.014 mg/kg/day, respectively. This first study in Morocco provides genetic data related to the frequency of genetic polymorphisms of CYP3A5 and opens the perspective to develop other pharmacogenetic studies. PMID- 22304538 TI - Effect of benzene exposure on fertility of male workers employed in bulk drug industries. AB - AIMS AND OBJECTIVES: Industrial workers are constantly exposed to benzene, especially at the production unit. The present investigation explores any association of the outcome of various reproductive malfunctions in terms of infertility and other related factors as a result of benzene exposure. METHODOLOGY: Blood and semen samples were collected from total 160 industrial workers exposed to benzene and 200 nonoccupationally exposed control subjects. We investigated macroscopic and microscopic semen parameters in the present study population. Body fluid benzene analysis was done by Head Space chromatography. The sperm DNA integrity was determined by modified alkaline single-cell gel electrophoresis or the comet assay method. RESULTS: No significant changes were observed in macroscopic semen parameters. A duration-dependent decrement in total sperm count and the percentage of motility was observed among the benzene-exposed industrial workers (p<0.05). A duration-dependent increment of abnormal sperm morphology was observed among the benzene-exposed industrial workers (p<0.01). A significant increase in comet tail length was observed in the exposed groups (p<0.01) in comparison to the controls. In regression analysis, the data were observed to be significant at the level of p<0.05 for Group II industrial workers (t=2.301). CONCLUSION: Sperm integrity is considered one of the major factors in male infertility. The sperm DNA damage is an important step from spermatogenesis to malfunctions such as infertility; therefore, the present study represents an important evaluation for correctly diagnosing the problem, precisely from the level of DNA itself. PMID- 22304539 TI - Diabetes and its chronic complications in the She ethnic minority group of China. AB - OBJECTIVE: According to recent reports, the development of type 2 diabetes in China has soared at an alarming rate. However, most of the investigations were based on Han people, who account for the majority of people in China. Little is known about the prevalence of diabetes its chronic complications in the She people, who have their own traditional lifestyle and hereditable background, different from other Asian population. The present study investigated the prevalence of type 2 diabetes and associated risk factors in the adult population of She nationals. SUBJECTS AND METHODS: A total of 5,385 participants entered into the analysis eventually, including 2,308 men and 3,077 women. An oral glucose tolerance test was performed in subjects without diagnosed diabetes. Liver function, cardiovascular risk (brachial-ankle pulse wave velocity, estimated glomerular filtration rate, and abnormal Minnesota codes findings), uric acid, and neuropathy were tested to assess the profiles of associated risks. RESULTS: In general, the self-reported diabetes rate was 9.5%. After age and sex standardization, the prevalence of diabetes was 6.1% (6.7% for men and 5.7% for women) in She Chinese people. In logistic regression models, age, family history of diabetes, alcohol use, total cholesterol, and triglycerides were all significantly associated with the risk of diabetes in this cross-sectional study (all P<0.05). In all, 47.4% had cardiovascular risks, 19.4% had liver dysfunction, and 6.2% had hyperuricemia. For women, compared with the first quartile, log-transformed homeostasis model assessment for insulin resistance of the fourth quartile was significantly higher (P<0.05), and log-transformed homeostasis model assessment for beta cells was also higher in the second, third, and fourth quartiles (all P<0.05). The prevalences of polyneuropathy in impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG/IGT, and diabetes mellitus (DM) were 16.1%, 13.1%, 18.6%, and 28.4% separately, which was higher than that in normal glucose tolerance. The prevalences of polyneuropathy in IFG/IGT and DM were higher than that in IGT. CONCLUSIONS: The present study revealed that a total of 6.1% She people suffered from type 2 diabetes, which was lower than the average level of China, but the standardized prevalence of prediabetes was higher, 20.6%. Early peripheral neuropathy screening should be performed in the prediabetes population. The Toronto Clinical Neuropathy Scoring System is convenient to assess diabetic polyneuropathy in clinical practice and should be tested regularly for people in prediabetes. Liver dysfunction, headache, and insomnia, appearing before type 2 diabetes, should be assessed regularly to avoid deterioration. PMID- 22304541 TI - Treatment-emergent adverse events associated with atypical antipsychotics. AB - INTRODUCTION: Atypical antipsychotics provide broad-spectrum effectiveness for the acute and/or preventative treatment of disparate psychiatric disorders. Atypical antipsychotics offer improved efficacy in some psychopathological domains when compared with typical antipsychotics. Notwithstanding, atypicals are not a catholicon and are associated with clinically significant and treatment limiting side effects (e.g., extrapyramidal symptoms and weight gain). AREAS COVERED: This article reviews commonly encountered adverse events attributable to the use of atypical antipsychotic agents. This review aims to provide a current overview of common adverse events associated with atypical agents with a particular emphasis on adverse events that frequently lead to treatment discontinuation (e.g., changes in weight, metabolism, extrapyramidal side effects, neuroendocrine changes, blood dyscrasias, and cardiovascular toxicity). EXPERT OPINION: Atypicals are not a catholicon and are associated with clinically significant and treatment-limiting side effects (e.g., extrapyramidal symptoms and weight gain). Improving the utility of these agents requires a familiarity and understanding of the heterogeneous tolerability and safety profiles of atypical agents as well as the therapeutic evidence for their efficacy. PMID- 22304542 TI - The association of eNOS G894T polymorphism with metabolic syndrome and erectile dysfunction. AB - INTRODUCTION: Accumulated evidences have outlined the potential relation between insulin resistance and endothelial dysfunction. The impaired ability of endothelium to synthesize or release nitric oxide may provide a common pathophysiological mechanism in the development of metabolic syndrome (MtS) and erectile dysfunction (ED). AIM: The aim of this article was to investigate the genetic susceptibility of endothelial nitric oxide synthase (eNOS) G894T polymorphism underlying the development of both disorders. METHODS: A total of 590 subjects with a mean (standard deviation) age of 55.3 years (4.1) were enrolled during a free health screening. Complete clinical data and questionnaires were taken for all subjects. Multivariate logistic regression analysis was used to determine the independent predictors of MtS and ED. The eNOS G894T polymorphism was determined using a polymerase chain reaction-restriction fragment length polymorphism method. MAIN OUTCOME MEASURES: The definition of MtS was according to the modified criteria developed by the Bureau of Health Promotion in Taiwan. Patients with ED were defined as those having a five-item International Index of Erectile Function (IIEF-5) <21. RESULTS: Our results showed that the eNOS 894T allele carriers had significantly higher prevalence of MtS and ED (odds ratio [OR]=1.64, 95% confidence interval [CI]=1.05~2.56, P=0.02 and OR=1.76, 95% CI=1.11~2.80, P=0.01, respectively) after adjustment for each other and age. Also the T allele carriers had significantly lower IIEF-5 score and more MtS components than G allele carriers (P<0.01 and P<0.01, respectively), which were significantly associated with an increment of the T allele number (P<0.05). CONCLUSIONS: The eNOS 894T allele carriers are at greater risk for both MtS and ED, suggesting that eNOS G894T gene polymorphism might play an implication as a common genetic susceptibility factor to develop both disorders. PMID- 22304543 TI - Sunlight-induced mortality of viruses and Escherichia coli in coastal seawater. PMID- 22304544 TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin in sediment samples from Love Canal storm sewers and creeks. PMID- 22304545 TI - Effect of simulated acid precipitation on algal fixation of nitrogen and carbon dioxide in forest soils. PMID- 22304546 TI - Distribution of atmospheric nitrogenous pollutants at a Los Angeles area smog receptor site. PMID- 22304548 TI - Factors affecting the soluble-suspended distribution of strontium-90 and cesium 137 in Dardanelle Reservoir, Arkansas. PMID- 22304547 TI - Aerosol filtration by a cocurrent moving granular bed: penetration theory. PMID- 22304549 TI - Mutagenicity and chemical characteristics of carbonaceous particulate matter from vehicles on the road. PMID- 22304550 TI - Notes. Isolation, identification, and determination of polycyclic aromatic hydrocarbons in sewage. PMID- 22304551 TI - Notes. A deep-towed pumping system for continuous underway sampling. PMID- 22304552 TI - Notes. Rates of reaction of hydroxyl radicals with 2-(dimethylamino)ethanol and 2 amino-2-methyl-1-propanol in the gas phase at 300 .+-. 2 K. PMID- 22304553 TI - Notes. Availability of elements of environmental importance in incinerated sludge ash. PMID- 22304554 TI - Comment on "Effect of nitrogen oxide emissions on ozone levels in metropolitan regions", "Effect of nitrogen oxide (NOx) emission rates on smog formation in the California South Coast Air Basin", and "Effect of hydrocarbon and nitrogen oxide (NOx) on photochemical smog formation under simulated transport conditions". PMID- 22304555 TI - Reply to comment on "Effect of nitrogen oxide emissions on ozone levels in metropolitan regions". PMID- 22304556 TI - Reply to comments on "effect of nitrogen oxide (NOx) emission rates on smog formation in the California south coast air basin". PMID- 22304557 TI - Reply to comment on "Effect of hydrocarbon and nitrogen oxide (NOx) on photochemical smog formation under simulated transport conditions". PMID- 22304558 TI - Comments on "Approach to forecasting daily maximun ozone levels in St. Louis". PMID- 22304560 TI - Nitrite and nitrite reductases: from molecular mechanisms to significance in human health and disease. AB - Nitrite, previously considered physiologically irrelevant and a simple end product of endogenous nitric oxide (NO) metabolism, is now envisaged as a reservoir of NO to be activated in response to oxygen (O(2)) depletion. In the first part of this review, we summarize and compare the mechanisms of nitrite dependent production of NO in selected bacteria and in eukaryotes. Bacterial nitrite reductases, which are copper or heme-containing enzymes, play an important role in the adaptation of pathogens to O(2) limitation and enable microrganisms to survive in the human body. In mammals, reduction of nitrite to NO under hypoxic conditions is carried out in tissues and blood by an array of metalloproteins, including heme-containing proteins and molybdenum enzymes. In humans, tissues play a more important role in nitrite reduction, not only because most tissues produce more NO than blood, but also because deoxyhemoglobin efficiently scavenges NO in blood. In the second part of the review, we outline the significance of nitrite in human health and disease and describe the recent advances and pitfalls of nitrite-based therapy, with special attention to its application in cardiovascular disorders, inflammation, and anti-bacterial defence. It can be concluded that nitrite (as well as nitrate-rich diet for long term applications) may hold promise as therapeutic agent in vascular dysfunction and ischemic injury, as well as an effective compound able to promote angiogenesis. PMID- 22304561 TI - Mechanism of inhibition of GluA2 AMPA receptor channel opening by 2,3 benzodiazepine derivatives: functional consequences of replacing a 7,8 methylenedioxy with a 7,8-ethylenedioxy moiety. AB - 2,3-Benzodiazepine (2,3-BDZ) compounds are a group of AMPA receptor inhibitors and are drug candidates for treating neurological diseases involving excessive AMPA receptor activity. We investigated the mechanism by which GluA2Q(flip) receptor channel opening is inhibited by two 2,3-BDZ derivatives, i.e., 1-(4 aminophenyl)-3,5-dihydro-7,8-ethylenedioxy-4H-2,3-benzodiazepin-4-one (2,3-BDZ-11 2) and its 1-(4-amino-3-chlorophenyl) analogue (2,3-BDZ-11-4). Both compounds have a 7,8-ethylenedioxy moiety instead of the 7,8-methylenedioxy feature present in the structure of GYKI 52466, the prototypic 2,3-BDZ compound. Using a laser pulse photolysis approach with a time resolution of ~60 MUs and a rapid solution flow technique, we characterized the effect of the two compounds on the channel opening process of the homomeric GluA2Q(flip) receptor. We found that both 2,3 BDZ-11-2 and 2,3-BDZ-11-4 are noncompetitive inhibitors with specificity for the closed-channel conformation of the GluA2Q(flip) receptor. However, 2,3-BDZ-11-4 is ~10-fold stronger, defined by its inhibition constant for the closed-channel conformation (i.e., K(I) = 2 MUM), than 2,3-BDZ-11-2. From double-inhibitor experiments, we determined that both compounds bind to the same site, but this site is different from two other known, noncompetitive binding sites on the GluA2Q(flip) receptor previously reported. Our results provide both mechanistic clues to improve our understanding of AMPA receptor regulation and a structure activity relationship for designing more potent 2,3-BDZ compounds with predictable properties for this new noncompetitive site. PMID- 22304562 TI - Differential expression of folate receptor-alpha, sodium-dependent multivitamin transporter, and amino acid transporter (B (0, +)) in human retinoblastoma (Y-79) and retinal pigment epithelial (ARPE-19) cell lines. AB - PURPOSE: The overall objective of this study was to investigate the differential expression of folate receptor-alpha (FR-alpha), sodium-dependent multivitamin transporter (SMVT), and amino acid transporter [B ((0, +))] in retinoblastoma (Y 79) and retinal pigment epithelial (ARPE-19) cells. METHODS: Polymerase chain reaction (PCR) analysis was performed to confirm the existence of FR-alpha, SMVT, and B ((0, +)) in Y-79 and ARPE-19 cell lines. Quantitative real-time PCR was also performed to determine the relative expression of FR-alpha, SMVT, and B ((0, +)) at mRNA level in these cell lines. Quantitative uptake of [(3)H] Folic acid, [(3)H] Biotin, and [(14)C] Arginine was studied in Y-79 and ARPE-19 cells. Further, saturation kinetics of [(3)H] Folic acid, [(3)H] Biotin, and [(14)C] Arginine was performed in the presence of various concentrations of respective cold substrates to determine the kinetic parameters (K(m) and V(max)) in Y-79 and ARPE-19 cells. RESULTS: PCR analysis had confirmed the existence of FR-alpha, SMVT, and B ((0, +)) in Y-79 and ARPE-19 cells. Quantitative real-time PCR analysis had shown significantly higher expression of FR-alpha, SMVT, and B ((0, +)) mRNA levels in Y-79 cells compared with ARPE-19 cells. Quantitative uptake of [(3)H] Folic acid, [(3)H] Biotin, and [(14)C] Arginine was found to be significantly higher in Y-79 cells relative to ARPE-19 cells. [(3)H] Folic acid uptake process followed saturation kinetics with apparent K(m) of 8.29 nM and V(max) of 393.47 fmol/min/mg protein in Y-79 cells and K(m) of 80.55 nM and V(max) of 491.86 fmol/min/mg protein in ARPE-19 cells. [(3)H] Biotin uptake process also displayed saturation kinetics with K(m) of 8.53 MUM and V(max) of 14.12 pmol/min/mg protein in Y-79 cells and K(m) of 138.25 MUM and V(max) of 38.85 pmol/min/mg protein in ARPE-19 cells. [(14)C] Arginine uptake process followed saturation kinetics with K(m) of 16.77 MUM and V(max) of 348.27 pmol/min/mg protein in Y-79 cells and K(m) of 52.03 MUM and V(max) of 379.21 pmol/min/mg protein in ARPE-19 cells. CONCLUSIONS: This work demonstrated for the first time the higher expression and affinity of FR-alpha, SMVT, and B ((0, +)) mRNA levels in retinoblastoma (Y-79) cells compared with retinal pigment epithelial (ARPE-19) cells. PMID- 22304563 TI - In vitro coagulation effects of ophthalmic doses of bevacizumab. AB - PURPOSE: In vitro coagulation effects of bevacizumab, a drug with potential risks for severe hemorrhagic and arterial thromboembolic events (ATEs), are unknown. The aim of this study was to evaluate the effects of bevacizumab, including the common ophthalmic dose of 1.25 mg, on the coagulation cascade. METHODS: Bevacizumab doses of 0.25, 0.5, 1.0, 1.25, 2.0, 2.5, and 4.0 mg were incubated at 37 degrees C in the presence of pooled normal plasma (PNP) to determine its biological activity via activated partial thromboplastin time (aPTT) and prothrombin time (PT) at 30 min, 1 h, and 2 h. The control consisted of 40% normal saline and 60% PNP. All evaluations were conducted in triplet. Coagulation at each time point was compared with the control group by analysis of variance with Tukey's post hoc test. A P value of <= 0.05 was considered significant. RESULTS: Mean bevacizumab aPTT ranged from 38.4 to 43.9 s, 37.4 to 43.1 s, and 39.0 to 43.2 s at 30 min, 1 h, and 2 h, respectively. Mean bevacizumab PT ranged from 15.7 to 16.8 s at 30 min, 14.6 to 16.2 s at 1 h, and 14.0 to 15.8 s at 2 h. For the control, aPTT was similar over time (40.1, 40.0, and 40.5 s), while PT decreased from 16.5 at 30 min to 15.4 s at 2 h. Bevacizumab decreased PT significantly at 2 h, compared with the PNP control, for the following doses: 0.25 mg [difference between means 1.04 s, 95% confidence interval (CI) 0.12 1.96], 1.25 mg (1.16 s, 95% CI 0.16-2.15), 2.5 mg (0.94 s, 95% CI 0.02-1.86), and 4 mg (1.41 s, 95% CI 0.41-2.40). Significant differences were not observed in PT at 30 min and 1 h as compared with controls. For all doses of bevacizumab, aPTT did not vary from controls at the 3 measured times. CONCLUSIONS: A common ophthalmic dose of bevacizumab 1.25 mg significantly increased in vitro coagulation. Further examination of the impact of ophthalmic bevacizumab on coagulation is warranted to provide insight into any putative link between ophthalmic bevacizumab and the risk for severe ATEs. PMID- 22304565 TI - Spatial localization and projection densities of brainstem mossy fibre afferents to the forelimb C1 zone of the rat cerebellum. AB - The present study uses a double retrograde tracer technique in rats to examine the spatial localization and pattern of axonal branching in mossy fibres arising from three major sources in the medulla-the external cuneate nucleus, the sensory trigeminal nucleus and the reticular formation, to two electrophysiologically identified parts of the cerebellar cortex that are linked by common climbing fibre input - the forelimb-receiving parts of the C1 zone in lobulus simplex and the paramedian lobule. In each experiment a small injection of rhodamine-tagged beads was injected into one cortical region and an injection of fluorescein tagged beads was injected into the other region. The main findings were: (i) the proportion of double-labelled cells in each of the three precerebeller sources of mossy fibres was positively correlated with those in the inferior olive; and (ii) the C1 zone in lobulus simplex was found to receive a greater density of projections from all three sources of mossy fibres than the C1 zone in the paramedian lobule. These data suggest that two rostrocaudally separated but somatotopically corresponding parts of the C1 zone receive common mossy fibre and climbing fibre inputs. However, the differences in projection densities also suggest that the two parts of the zone differ in the extent to which they receive mossy fibre signals arising from the same precerebellar nuclei. This implies differences in function between somatotopically corresponding parts of the same cortical zone, and could enable a higher degree of parallel processing and integration of information within them. PMID- 22304566 TI - Photoprotective potential of strawberry (Fragaria * ananassa) extract against UV A irradiation damage on human fibroblasts. AB - Exposure to UV-A radiation is known to induce discrete lesions in DNA and the generation of free radicals that lead to a wide array of skin diseases. Strawberry (Fragaria * ananassa) contains several polyphenols with strong antioxidant and anti-inflammatory activities. Because the major representative components of strawberry are anthocyanins, these may significantly contribute to its properties. To test this hypothesis, methanolic extracts from the Sveva cultivar were analyzed for anthocyanin content and for their ability to protect human dermal fibroblasts against UV-A radiation, as assayed using 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenytetrazolium bromide and Comet assays. Five anthocyanin pigments were identified using high-performance liquid chromatography diode array detection-electrospray ionization/mass spectrometry. Moreover, the strawberry extract showed a photoprotective activity in fibroblasts exposed to UV A radiation, increasing cellular viability, and diminishing DNA damage, as compared to control cells. Overall, our data show that strawberry contains compounds that confer photoprotective activity in human cell lines and may protect skin against the adverse effects of UV-A radiation. PMID- 22304567 TI - Characterization of silver nanoparticle products using asymmetric flow field flow fractionation with a multidetector approach--a comparison to transmission electron microscopy and batch dynamic light scattering. AB - Due to the already prevalent and increasing use of silver-nanoparticle (Ag-NP) products and the raised concerns in particular for the aquatic environment, analytical techniques for the characterization of such products are of need. However, because Ag-NP products are of different compositions and polydispersities, analysis especially of the size distribution is challenging. In this work, an asymmetric flow field flow fractionation (A4F) multidetector system (UV/vis, light scattering, inductively coupled plasma mass spectrometry - ICPMS), in combination with a method to distinguish and quantify the particle and dissolved Ag fractions (ICPMS after ultracentrifugation), for the characterization of Ag-NP products with different degrees of polydispersities is presented. For validation and to outline benefits and limitations, results obtained from batch dynamic light scattering (batch-DLS) and transmission electron microscopy (TEM) were compared. With the developed method a comprehensive understanding in terms of dissolved Ag and Ag-NP concentration as well as an element selective, mass- and number particle size distribution (PSD) was obtained. In relation to batch-DLS, the reliability of the data was improved significantly. In comparison to TEM, faster measurement times and the ability to determine the samples directly in dispersions are clearly advantageous. The proposed setup shows potential for a rapid- and reliable characterization method of virtually any polydisperse metallic NP dispersion, many of them available on the market already. PMID- 22304568 TI - GP cooperative and emergency department: an exploration of patient flows. AB - RATIONALE, AIMS AND OBJECTIVES: In most countries, different health care providers are involved in emergency care. In the Netherlands, out-of-hours care is provided by general practitioner cooperatives (GPCs) and emergency departments (EDs). Our aim was to describe the flow of patients attending emergency care in these settings. METHOD: A retrospective record review was performed, concerning patients who had visited a GPC or ED. Recorded information included urgency, diagnostic tests, and follow-up contacts. Descriptive figures were determined for patient flows in GPC and ED for urgent contacts and non-urgent contacts. RESULTS: We included 319 GPC contacts and 356 ED contacts, of which 78% were non-urgent. The majority of GPC contacts were completed at the GPC without follow-up; 37% of non-urgent patients had a follow-up contact, usually with primary care. Only 5% of non-urgent GPC patients received diagnostic tests compared to 63% of non urgent ED patients (mostly X-rays). The majority of non-urgent ED patients (88%) had a follow-up contact, usually at an outpatient clinic (67%). Most non-urgent ED patients (83%) who received a diagnostic test also had an outpatient clinic follow-up contact. Of urgent ED patients, the majority had a follow-up contact (85%), mostly with an outpatient clinic (74%). CONCLUSION: Although most out-of hours care patients present non-urgent health problems, at the ED they are more likely to receive diagnostic tests and follow-up contacts. This may reflect differences in patient populations between the ED and GPC or suggest opportunities for improving efficiency of planning follow-up contacts. PMID- 22304569 TI - Functional polymorphism located in MMP-9 gene promoter is strongly associated with obesity. AB - The adipose tissue expansion is accompanied by remodeling of extracellular matrix performed by matrix metalloproteinases (MMPs). Higher plasma and tissue MMP-9 levels are found in obese; therefore, we evaluated if the functional C(-1562)T polymorphism (rs3918242) located in promoter region of the MMP-9 gene is associated with obesity in women. We studied 112 lean and 114 obese women. Plasma MMP-9 and tissue inhibitor of MMP-9 (TIMP)-1 were measured using enzyme-linked immunosorbent assay. We found different genotype frequencies between lean and obese women (p=0.008), prevailing T-allele in obese (2.3-fold). However, although obese women present higher levels of plasma MMP-9, lack of modulation by the polymorphism was found (all p>0.05). Our findings suggest that C(-1562)T polymorphism may contribute to pathogenetic mechanisms involved in the development of obesity in women. PMID- 22304571 TI - CCND1 G870A polymorphism with altered cyclin D1 transcripts expression is associated with the risk of glioma in a Chinese population. AB - A common polymorphism (G870A) in the exon 4/intron 4 boundary of CCND1 gene has been linked to an alternate transcript, cyclin D1b, which preferentially encodes a protein with an increased transforming capability compared with the full-length D1a. Therefore, the CCND1 G870A polymorphism may influence an individual's susceptibility to the development of certain tumors. In the present study, we investigated the association of CCND1 G870A polymorphism with glioma cancer risk in a northern Chinese population. By polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, CCND1 G870A genotyping was carried out among 170 glioma patients and 170 age, gender-matched healthy control subjects. The CCND1 870 A allele was more frequently observed in patients than in controls (0.57 vs. 0.48, p=0.03), and an increased risk of glioma cancer was observed for the AA genotype compared with the GG and AG genotypes (odds ratio [OR]=1.828; 95% confidence interval [CI]: 1.150-2.908, p=0.01), particularly among female groups, or ages <=45 groups (OR=2.204, 95% CI: 1.220-3.981, p=0.008). Significant associations were also observed between the AA genotype and glioma risk in the subgroups of World Health Organization (WHO) grade II gliomas and grade III gliomas. Further reverse transcriptase-polymerase chain reaction analysis (RT-PCR) also revealed a stronger positive correlation between the AA genotype and higher cyclin D1b expression among glioma patients either in the mean quantitative value, or the cyclin D1b/cyclin D1a ratio in the same tumor tissue (p=0.008, p=0.004, respectively). In conclusion, our data indicate that the CCND1 G870A polymorphism modulated oncogenic cyclin D1b expression in glioma tissues and may be associated with an increased risk of gliomas in Chinese population. PMID- 22304572 TI - Divergent amine-catalyzed [4 + 2] annulation of Morita-Baylis-Hillman allylic acetates with electron-deficient alkenes. AB - An amine-catalyzed [4 + 2] annulation of Morita-Baylis-Hillman allylic acetates 2 with electron-deficient alkenes or diazenes has been developed for efficient syntheses of highly functionalized cyclohexenes, tetrahydropyridazines, and important spirocycles. This reaction unveils a new reactivity pattern of the intensely studied allylic compounds 2 acting as a C(4) synthon in Lewis base catalyzed annulation reactions and also showcases divergent catalysis between tertiary amines and phosphines. PMID- 22304573 TI - Variation at GLCCI1 and FCER2: one step closer to personalized asthma treatment. PMID- 22304574 TI - Tag SNPs of the ancestral haplotype 57.1 do not substitute HLA-B*57:01 typing for eligibility to abacavir treatment in the Italian population. PMID- 22304575 TI - In Mexican Mestizos the HCP5 rs2395029 SNP may be a genetic marker for screening abacavir hypersensitivity. PMID- 22304577 TI - Interview with Isaac S. Kohane conducted by Sarah Miller. PMID- 22304578 TI - Highlights from the latest articles in diabetes pharmacogenomics. PMID- 22304580 TI - Cytidine deaminase genetic variants influence RNA expression and cytarabine cytotoxicity in acute myeloid leukemia. AB - AIM: Cytidine deaminase (CDA) irreversibly deaminates cytarabine (Ara-C), a key component of acute myeloid leukemia (AML) induction and consolidation therapy. CDA overexpression results in Ara-C resistance, while decreased expression is associated with toxicity. We evaluated factors influencing variation in CDA mRNA expression in adult AML patients and normal controls, and how they contributed to Ara-C cytotoxicity in AML cells. MATERIALS & METHODS: CDA mRNA expression in 100 de novo AML patients and 36 normal controls were determined using quantitative reverse-transcriptase PCR. Genetic variants in the CDA gene were screened by direct sequencing. IC50 of Ara-C was determined by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide assay. RESULTS: CDA RNA expression as well as Ara C IC50 showed wide variation in AML samples and normal controls. Fourteen sequence variants were identified, three of which (-33delC, intron 2 TCAT repeat and the 3'untranslated region 816delC variants) showed significant association with RNA expression and the nonsynonymous coding variant 79A>C was associated with Ara-C cytotoxicity. CONCLUSION: CDA genetic variants explain the variation in RNA expression and may be candidates for individualizing Ara-C therapy. PMID- 22304581 TI - 6-mercaptopurine influences TPMT gene transcription in a TPMT gene promoter variable number of tandem repeats-dependent manner. AB - AIM: TPMT activity is characterized by a trimodal distribution, namely low, intermediate and high methylator. TPMT gene promoter contains a variable number of GC-rich tandem repeats (VNTRs), namely A, B and C, ranging from three to nine repeats in length in an A(n)B(m)C architecture. We have previously shown that the VNTR architecture in the TPMT gene promoter affects TPMT gene transcription. MATERIALS, METHODS & RESULTS: Here we demonstrate, using reporter assays, that 6 mercaptopurine (6-MP) treatment results in a VNTR architecture-dependent decrease of TPMT gene transcription, mediated by the binding of newly recruited protein complexes to the TPMT gene promoter, upon 6-MP treatment. We also show that acute lymphoblastic leukemia patients undergoing 6-MP treatment display a VNTR architecture-dependent response to 6-MP. CONCLUSION: These data suggest that the TPMT gene promoter VNTR architecture can be potentially used as a pharmacogenomic marker to predict toxicity due to 6-MP treatment in acute lymphoblastic leukemia patients. PMID- 22304582 TI - Pharmacogenomics of the heptahelical receptor regulators G-protein-coupled receptor kinases and arrestins: the known and the unknown. AB - Heptahelical G-protein-coupled receptors are the most diverse and therapeutically important family of receptors, playing major roles in the physiology of various organs and tissues. They couple their ligand binding to G-protein activation, which then transmits intracellular signals. G-protein signaling is terminated by phosphorylation of the receptor by the family of G-protein-coupled receptor kinases (GRKs), followed by arrestin (Arr) binding, which uncouples the phosphorylated receptor from the G-protein and subsequently targets the receptor for internalization. Moreover, Arrs can transmit signals in their own right during receptor internalization. Genetic polymorphisms in receptors, as well as in GRK and Arr family members per se, which affect regulation of receptor signaling and function, have just started being identified and characterized. The present review will discuss what is known so far in this evolving field of GRK/Arr pharmacogenomics, as well as highlight important areas likely to produce invaluable information in the future. PMID- 22304583 TI - Computational tools for discovery and interpretation of expression quantitative trait loci. AB - Expression quantitative trait locus (eQTL) analysis is rapidly moving from a cutting-edge concept in genomics to a mature area of investigation, with important connections to genome-wide association studies for human disease, pharmacogenomics and toxicogenomics. Despite the importance of the topic, many investigators must develop their own code or use tools not specifically suited for eQTL analysis. Convenient computational tools are becoming available, but they are not widely publicized, and investigators who are interested in discovery or eQTL, or in using them to interpret genome-wide association study results may have difficulty navigating the available resources. The purpose of this review is to help investigators find appropriate programs for eQTL analysis and interpretation. PMID- 22304584 TI - A capillary electrophoresis method for genotyping the 9-bp exon 1 insertion/deletion in BDKRB2. AB - AIM: To develop and apply a novel genotyping method for the 9-bp exon 1 insertion/deletion polymorphism in BDKRB2. MATERIALS & METHODS: DNA from 718 patients with heart failure was extracted using standard methods and a region containing exon 1 of BDKRB2 was amplified with PCR. The PCR product was separated using the Qiagen QIAxcel(r) capillary electrophoresis system. The bp size of the PCR product was calculated and the genotypes determined using Qiagen BioCalculator(r) software. RESULTS: Capillary electrophoresis accurately genotyped samples with >99% call rate and 700 s run time per row of a 96-well plate (i.e., less than 1 min per sample). The frequency of the deletion was 49% in the Caucasian patients (n = 441) and 45% in the African-American (n = 277). CONCLUSION: Capillary electrophoresis is a rapid, accurate and sensitive method for genotyping the 9-bp exon 1 insertion/deletion polymorphism in BDKRB2. PMID- 22304586 TI - The 4-hour rule: does lowering the temperature treat the system? PMID- 22304587 TI - Emergency department overcrowding: the solution to any problem is a matter of relativity. PMID- 22304588 TI - Aboriginal and Torres Strait Islander mental health: paradise lost? PMID- 22304589 TI - Improving the health of Australian children entering out-of-home care. PMID- 22304590 TI - Clinical pathways: a departure from the art of medicine. PMID- 22304591 TI - Clinical deterioration in hospital inpatients: the need for another paradigm shift. PMID- 22304592 TI - Emergency and acute medical admissions: insights from US and UK visits by a Melbourne tertiary health service. PMID- 22304593 TI - A plea for professional independence. PMID- 22304594 TI - The Sydney University Medical Program: highlights and lessons. PMID- 22304595 TI - Wind farms and health: who is fomenting community anxieties? PMID- 22304596 TI - What is wrong with Medicare? PMID- 22304597 TI - Should doctors feel able to practise according to their personal values and beliefs? PMID- 22304598 TI - Should more Australian doctors be salaried than paid by fee-for-service? PMID- 22304599 TI - Increasing numbers of inmate separations from Australian prisons. PMID- 22304600 TI - Impact of incident location on long-term pedestrian mortality and major trauma in inner Sydney. PMID- 22304601 TI - An unrecognised case of tenofovir-associated Fanconi syndrome. PMID- 22304602 TI - Barriers to recruitment in cancer trials: no longer medical oncologists' attitudes. PMID- 22304603 TI - Conflict of interest guidelines for clinical guidelines. PMID- 22304604 TI - Memory loss. AB - Most older people with memory loss do not have dementia. Those with mild cognitive impairment are at increased risk of progressing to dementia, but no tests have been shown to enhance the accuracy of assessing this risk. Although no intervention has been convincingly shown to prevent dementia, data from cohort studies and randomised controlled trials are compelling in indicating that physical activity and treatment of hypertension decrease the risk of dementia. There is no evidence that pharmaceutical treatment will benefit people with mild cognitive impairment. In people with Alzheimer's disease, treatment with a cholinesterase inhibitor or memantine (an N-methyl- D-aspartate receptor antagonist) may provide symptomatic relief and enhance quality of life, but does not appear to alter progression of the illness. Non-pharmacological strategies are recommended as first-line treatments for behavioural and psychological symptoms of dementia, which are common in Alzheimer's disease. Atypical antipsychotics have modest benefit in reducing agitation and psychotic symptoms but increase the risk of cardiovascular events. The role of antidepressants in managing depressive symptoms in patients with mild cognitive impairment is uncertain and may increase the risk of delirium and falls. PMID- 22304605 TI - Mental health of Indigenous Australians: a review of findings from community surveys. AB - OBJECTIVE: To assemble what is known about the mental health of Indigenous Australians from community surveys. DATA SOURCES: A systematic search was carried out of publications and data sources since 2000 using PubMed, PsycINFO, Australian Medical Index, the National Library of Australia and datasets known to the authors. STUDY SELECTION: Surveys had to involve representative sampling of a population, identify Aboriginal and Torres Strait Islander people and include a measure of mental health. DATA EXTRACTION: 11 surveys were found. Data were extracted on prevalence rates for Indigenous people by age and sex, along with comparison data from the general population, where available. DATA SYNTHESIS: Across seven studies, Indigenous adults were consistently found to have a higher prevalence of self-reported psychological distress than the general community. However, two studies of Indigenous adolescents did not find a higher prevalence of psychological distress. Two surveys of parents and carers of Indigenous children and adolescents found a higher prevalence of behaviour problems. CONCLUSIONS: There is an inequality in mental health between Indigenous and non Indigenous Australians that starts from an early age. This needs to be a priority for research, preventive action and health services. PMID- 22304606 TI - Emergency department overcrowding, mortality and the 4-hour rule in Western Australia. AB - OBJECTIVE: To assess whether emergency department (ED) overcrowding was reduced after the introduction of the 4-hour rule in Western Australia and whether any changes in overcrowding were associated with significant changes in patient mortality rates. DESIGN, SETTING AND PATIENTS: Quasi-experimental intervention study using dependent pretest and post-test samples. Hospital and patient data were obtained for three tertiary hospitals and three secondary hospitals in Perth, WA, for 2007-08 to 2010-11. MAIN OUTCOME MEASURES: Mortality rates; overcrowding rates. RESULTS: No change was shown in mortality from 2007-08 to 2010-11 for the secondary hospitals and from 2007-08 to 2009-10 for the tertiary hospitals. ED overcrowding (as measured by 8-hour access block) at the tertiary hospitals improved dramatically, falling from above 40% in July 2009 to around 10% by early 2011, and presentations increased by 10%, while the mortality rate fell significantly (by 13%; 95% CI, 7%-18%; P < 0.001) from 1.12% to 0.98% between 2009-10 and 2010-11. Monthly mortality rates decreased significantly in two of the three tertiary hospitals concurrently with decreased access block and an increased proportion of patients admitted in under 4 hours. CONCLUSION: Introduction of the 4-hour rule in WA led to a reversal of overcrowding in three tertiary hospital EDs that coincided with a significant fall in the overall mortality rate in tertiary hospital data combined and in two of the three individual hospitals. No reduction in adjusted mortality rates was shown in three secondary hospitals where the improvement in overcrowding was minimal. PMID- 22304607 TI - Emergency department targets: a watershed for outcomes research? PMID- 22304608 TI - Demand at the emergency department front door: 10-year trends in presentations. AB - OBJECTIVES: To measure the increase in volume and age-specific rates of presentations to public hospital emergency departments (EDs), as well as any changes in ED length of stay (LOS); and to describe trends in ED utilisation. DESIGN, PATIENTS AND SETTING: Population-based retrospective analysis of Department of Health public hospital ED data for metropolitan Melbourne for 1999 00 to 2008-09. MAIN OUTCOME MEASURES: Presentation numbers; presentation rates per 1000 person-years; ED LOS. RESULTS: ED presentations increased from 550,662 in 1999-00 to 853,940 in 2008-09. This corresponded to a 32% rise in rate of presentation (95% CI, 29%-35%), an average annual increase of 3.6% (95% CI, 3.4% 3.8%) after adjustment for population changes. Almost 40% of all patients remained in the ED for >=4 hours in 2008-09, with LOS increasing over time for patients who were more acutely unwell. The likelihood of presentation rose with increasing age, with people aged>=85 years being 3.9 times as likely to present as those aged 35-59 years (95% CI, 3.8-4.0). The volume of older people presenting more than doubled over the decade. They were more likely to arrive by emergency ambulance and were more acutely unwell than 35-59 year olds, with 75% having an LOS>=4 hours and 61% requiring admission in 2008-09. CONCLUSION: The rise in presentation numbers and presentation rates per 1000 person-years over 10 years was beyond that expected from demographic changes. Current models of emergency and primary care are failing to meet community needs at times of acute illness. Given these trends, the proposed 4-hour targets in 2012 may be unachievable unless there is significant redesign of the whole system. PMID- 22304609 TI - Psychosis in Indigenous populations of Cape York and the Torres Strait. AB - OBJECTIVE: To describe and characterise treated psychotic disorders in the Indigenous populations of Cape York and the Torres Strait. DESIGN: Cross sectional analysis of patients with a psychotic disorder identified by treating psychiatrists. SETTING AND PARTICIPANTS: Indigenous patients aged>=15 years in Cape York and Torres Strait communities receiving treatment for a psychotic disorder over 3 months in 2010. MAIN OUTCOME MEASURES: Prevalence of psychosis diagnoses, intellectual disability, and substance use comorbidities. RESULTS: 171 patients were included. The prevalence rate in this population was 1.68%, higher for males (2.60%) than females (0.89%), and twice as high in the Aboriginal (2.05%) than in the Torres Strait Islander (0.95%) population. High rates of alcohol and cannabis use were found. Comorbid intellectual disability was common and more frequent among Aboriginal patients. CONCLUSIONS: The burden of psychosis in the Indigenous population of Cape York and the Torres Strait is high. Further research is needed to understand the social determinants of these disorders and to design effective social and clinical measures to alleviate this burden. PMID- 22304610 TI - Targeted primary care-based mental health services for young Australians. AB - OBJECTIVE: To assess the extent to which youth-specific, mental health care centres engage young people (12-25 years of age) in treatment, and to report the degree of psychological distress, and the diagnostic type, stage of illness, and psychosocial and vocational impairment evident in these young people. DESIGN AND SETTING: Standardised clinical and self-report assessments of consecutive presentations at two youth-specific centres from October 2007 to December 2009. Both sites are operated by the Brain and Mind Research Institute in Sydney, Australia, as part of headspace: the National Youth Mental Health Foundation mental health care service. RESULTS: Of 1260 young people assessed, 53% were male, and the mean (SD) age was 18.1 (3.9) years. Over 40% of the young people were self-referred, or their assessment was arranged by family or friends, or by other social agencies; 30% of young people were referred from other primary health providers. Almost 70% reported high or very high levels of psychological distress. More than 60% of subjects reported having 2 or more days "unable to function" within the past month, and clinicians rated over 50% as having at least moderate difficulty in social/occupational functioning. Importantly, 25% of subjects were receiving income support. Two-thirds of subjects were rated as being at the early stage of an illness, and almost half were diagnosed with anxiety or depressive syndromes. CONCLUSIONS: Targeted youth-specific mental health services, based in primary care settings, are able to engage young Australians, particularly young men, in treatment. Many of these young people report established patterns of psychosocial and vocational impairment. PMID- 22304611 TI - Doctors and writing: stranger than fiction? PMID- 22304614 TI - Estimated prevalence of dengue viremia in Puerto Rican blood donations, 1995 through 2010. AB - BACKGROUND: Dengue virus (DENV) nucleic acid amplification testing of blood donations during epidemics in endemic locations, including Puerto Rico, has suggested possible sizable transfusion transmission risk. Estimates of the long term prevalence of DENV viremic donations will help evaluate the potential magnitude of this risk in Puerto Rico. STUDY DESIGN AND METHODS: Estimates of the prevalence of DENV viremia in the Puerto Rican population at large from 1995 through 2010 were derived from dengue case reports and their onset dates obtained from islandwide surveillance, estimates of case underreporting, and extant data on the duration of DENV viremia and the unapparent-to-apparent dengue infection ratio. Under the assumptions that viremia prevalence in blood donors was similar to that of the population at large and that symptomatic persons do not donate, statistical resampling methods were used to estimate the prevalence of dengue viremia in blood donations. RESULTS: Over the 16-year period, the maximum and mean daily prevalences of dengue viremia (per 10,000) in blood donations in Puerto Rico were estimated at 45.0 (95% confidence interval [CI], 36.5-55.4) and 7.0 (95% CI, 3.9-10.1), respectively. Prevalence varied considerably by season and year. CONCLUSION: These data suggest a substantial prevalence of DENV viremia in Puerto Rican blood donations, particularly during outbreaks. PMID- 22304615 TI - What is your diagnosis? CBC data and blood smear from a cynomolgus macaque (Macaca fascicularis). PMID- 22304617 TI - What are the therapeutic effects of high-dose intravenous prednisolone in methanol-induced toxic optic neuropathy? PMID- 22304618 TI - Rebamipide increases mucin-like substance contents and periodic acid Schiff reagent-positive cells density in normal rabbits. AB - PURPOSE: The effects of rebamipide on the number of periodic acid Schiff reagent (PAS)-positive cells in the conjunctiva, the mucin content in the cornea and conjunctiva of normal rabbits, and desiccation-induced corneal damage in vivo were examined. METHODS: Rebamipide (0.1%-3%) was applied 6 times a day for 14 days, and the PAS-positive cell count in the bulbar conjunctiva was measured by impression cytology. The amount of conjunctival and corneal mucin-like substances was measured by Alcian blue binding. The corneal damage model was created by desiccation from air flow at room temperature. The level of corneal damage was determined by scoring the area stained with rose bengal and fluorescein dye. RESULTS: Rebamipide increased the number of PAS-positive cells in the conjunctiva when instilled at concentrations of 0.3% or higher, and 1% rebamipide increased the amount of mucin-like substances of the conjunctiva and cornea. Moreover, 1% rebamipide was also found to lower the rose bengal scores of the cornea in the corneal damage model by desiccation. CONCLUSIONS: Rebamipide is a possible candidate drug for treatment of cornea and conjunctival epithelial damage due to its mucin-like substance increasing action, for instance, in the treatment of dry eye disease. PMID- 22304619 TI - Functional-morphological changes after intravitreal injection of triamcinolone acetonide for macular edema with branch retinal vein occlusion. AB - PURPOSE: To evaluate functional and morphological changes of the macula after intravitreal injection of triamcinolone acetonide (IVTA) for macular edema with branch retinal vein occlusion (BRVO). METHODS: Twenty patients with BRVO (mean age: 69.7 +/- 9.8 years; 14 women and 6 men) received IVTA. Macular function was documented by microperimetry and best-corrected visual acuity (BCVA) was determined. Retinal thickness and retinal volume were measured by optical coherence tomography, and mean retinal sensitivity was calculated for each of 9 macular subfields. RESULTS: Mean BCVA significantly improved 6 months after IVTA. Mean retinal sensitivity, retinal thickness, and retinal volume significantly improved after 6 months in 4, 8, and 8 subfields, respectively. On multivariate analysis, improvement of retinal sensitivity was significantly correlated with the percent changes of both retinal thickness and retinal volume in 2 subfields [superior inner (the occlusion site) and temporal outer], although improvement of visual acuity was not significantly correlated with the percent change of macular edema in any of the 9 subfields. CONCLUSIONS: These findings suggest that IVTA can improve both functional and morphological changes due to macular edema in BRVO patients, and that morphological improvement after IVTA might be useful for assessing the functional prognosis of BRVO with macular edema. PMID- 22304620 TI - A randomized, double-blind comparison shows the addition of oxygenated glycerol triesters to topical mentholated cream for the treatment of acute musculoskeletal pain demonstrates incremental benefit over time. AB - BACKGROUND: Topical analgesics are important products in the armamentarium for pain relief. METHODS AND FINDINGS: This study compared a topical analgesic product containing menthol to the same product with the addition of oxygenated glycerol triesters (OGTs) (also called essential oxygen oil) in 66 healthy adult subjects with acute musculoskeletal pain. Patients were randomized in a single center, double-blind study to receive mentholated cream (MC) only or MC containing OGTs. Patients self-reported their pain intensity, lifestyle limitations, and evaluation of the mobility of the painful joint or muscle at baseline and three times daily over a seven-day course on a 100-mm visual analog scale (VAS). Patients in both groups experienced statistically significant pain relief on Day 8 over baseline, with the MC plus OGT-treated group reporting statistically significantly greater pain relief than the MC group (P = 0.016). In addition, patients treated with the combination product experienced an incremental decrease in pain during each of the 7 days of treatment in addition, and they had lower VAS scores and greater lifestyle and mobility improvements than the MC group. Both products were well tolerated with no serious adverse events reported and no signs of significant skin reactions in either group. CONCLUSION: Based on this study, a MC containing OGTs is safe, effective, and provided significantly better pain relief than MC alone. The combination of oxygenated glycerol trimesters and MC provided significant pain relief and offered continued improvement in pain relief over time. PMID- 22304621 TI - Interrelationships among invasive and non-invasive indicators of biological maturation in adolescent male soccer players. AB - The relationships among indicators of biological maturation were evaluated and concordance between classifications of maturity status in two age groups of youth soccer players examined (11-12 years, n = 87; 13-14 years, n = 93). Data included chronological age (CA), skeletal age (SA, Fels method), stage of pubic hair, predicted age at peak height velocity, and percent of predicted adult height. Players were classified as on time, late or early in maturation using the SA-CA difference, predicted age at peak height velocity, and percent of predicted mature height. Factor analyses indicated two factors in players aged 11-12 years (maturity status: percent of predicted mature height, stage of pubic hair, 59% of variance; maturity timing: SA/CA ratio, predicted age at peak height velocity, 26% of variance), and one factor in players aged 13-14 years (68% of variance). Kappa coefficients were low (0.02-0.23) and indicated poor agreement between maturity classifications. Spearman rank-order correlations between categories were low to moderate (0.16-0.50). Although the indicators were related, concordance of maturity classifications between skeletal age and predicted age at peak height velocity and percent predicted mature height was poor. Talent development programmes call for the classification of youth as early, average, and late maturing for the purpose of designing training and competition programmes. Non-invasive indicators of maturity status have limitations for this purpose. PMID- 22304623 TI - Biological implications of oxidation and unidirectional chiral inversion of D amino acids. AB - Recent progress in chiral separation of D- and L-amino acids by chromatography ascertained the presence of several free Damino acids in a variety of mammals including humans. Unidirectional chiral inversion of many D-amino acid analogs such as exogenous NG-nitro-D-arginine (D-NNA), endogenous D-leucine, D phenylanine and D-methionine have been shown to take place with inversion rates of 4-90%, probably dependent on various species D-amino acid oxidase (DAAO) enzymatic activities. DAAO is known to catalyze the oxidative deamination of neutral and basic D-amino acids to their corresponding alpha-keto acids, hydrogen peroxide and ammonia, and is responsible for the chiral inversion. This review provides an overview of recent research in this area: 1) oxidation and chiral inversion of several D-amino acid analogs in the body; 2) the indispensable but insufficient role of DAAO particularly in the kidneys and brain for the oxidation and chiral inversion of D-amino acids analogs; and 3) unidentified transaminase(s) responsible for the second step of chiral inversion. The review also discusses the physiological significance of oxidation and chiral inversion of D-amino acids, which is still a subject of dispute. PMID- 22304626 TI - Treating erectile dysfunction and central neurological diseases with oral phosphodiesterase type 5 inhibitors. Review of the literature. AB - INTRODUCTION: Erectile dysfunction (ED) is reported in a high percentage of patients with central neurological disorders (CND). AIM: An up-to-date review on oral phosphodiesterase 5 inhibitors (PDE5): sildenafil, tadalafil, and vardenafil for individuals with CND and ED. MAIN OUTCOME MEASURES: Various questionnaires on ED, such as the International Index of Erectile Function composed of 15 questions. METHODS: Internationally published clinical studies evaluating the efficacy and safety of PDE5 on subjects with CND and ED were selected. RESULTS: Overall, 28 articles on PDE5 used to treat patients with CND and ED were included. With each of the three PDE5 compared to placebo or erectile baseline, literature reported significant statistical improvement (P < 0.01; P < 0.05) only in patients with spinal cord injury (SCI). PDE5 efficacy was documented for SCI patients up to 10 years. The most frequent predicable factor for PDE5 success was the presence of upper motoneuron lesion. Each of the three clinical sildenafil studies documented statistically significant improvement on erectile function in Parkinson's patients (P < 0.01; P < 0.05). Two studies reported discordant results about sildenafil's effectiveness on multiple sclerosis (MS) patients; one on tadalafil showed significant statistical efficacy on erection versus baseline (P < 0.01; P < 0.05). The only spina bifida article determined that sildenafil remarkably improved erectile function. Overall, drawbacks were mostly slight-moderate, except in subjects with multiple system atrophy where sildenafil caused severe hypotension. CONCLUSIONS: PDE5 represent first line ED therapy only for SCI patients, though treatment results through meta-analysis were not possible. Encouraging results are reported for Parkinson's and MS patients. PDE5 use for other CND patients is limited for various reasons, such as ED and concomitant libido impairment caused by depression and/or sexual endocrinology dysfunctions, and because PDE5 may cause a worsening of neurological illness. Medical centers staffed by health professionals able to counsel patients on the possible use of PDE5 are needed. PMID- 22304627 TI - Triggering ovulation with 250 MUg or 500 MUg of r-hCG in oocyte donors treated with antagonist protocol has no effect on the number of mature oocytes retrieved: a randomized clinical trial. AB - The aim of this study is to compare two r-hCG doses to trigger ovulation (250 MUg vs. 500 MUg of r-hCG) in an oocyte donation program. A prospective, randomized study was conducted in 118 oocyte donors. Group DI received 250 MUg and Group DII received 500 MUg of r-hCG. Both the groups were homogeneous. No significant differences were found in the total dose of gonadotropins, duration of the treatment, total number of oocytes, or Metaphase II (MII)oocytes. The pregnancy rate per embryo transfer in the corresponding recipients was similar for both the groups (58.2% for DII recipients and 56.1% for DI recipients). Mild hyperstimulation was observed in 17 donors in Group DI (29%) and in 23 donors in Group DII (39%). No cases of severe ovarian hyperstimulation syndrome (SOHSS) were observed. In conclusion, a double dose of r-hCG in oocyte donors to trigger ovulation after stimulation with r-FSH and antagonist does not translate into a higher number of MII oocytes retrieved or into higher pregnancy rates among recipients. Our results confirm that the optimal dose to induce the final oocyte maturation with r-hCG is 250 MUg, and that a higher dose does not add any benefit. PMID- 22304628 TI - Levodopa influences striatal activity but does not affect cortical hyper-activity in Parkinson's disease. AB - Motor studies of Parkinson's disease (PD) have shown cortical hypo-activity in relation to nigrostriatal dopamine depletion. Cognitive studies also identified increased cortical activity in PD. We have previously suggested that the hypo activity/hyper-activity patterns observed in PD are related to the striatal contribution. Tasks that recruit the striatum in control participants are associated with cortical hypo-activity in patients with PD, whereas tasks that do not result in cortical hyper-activity. The putamen, a structure affected by the neurodegeneration observed in PD, shows increased activation for externally triggered (ET) and self-initiated (SI) movements. The first goal of this study was to evaluate the effect of levodopa on the putamen's response to ET and SI movements. Our second goal was to assess the effect of levodopa on the hypo activity/hyper-activity patterns in cortical areas. Patients with PD on and off levodopa and healthy volunteers performed SI, ET and control finger movements during functional magnetic resonance imaging. Healthy participants displayed significant differences in putamen activity in ET and SI movements. These differences were reduced in patients off medication, with non-task-specific increases in activity after levodopa administration. Furthermore, the ventrolateral prefrontal cortex showed significant increases in activity during SI movements in healthy controls, whereas it was hypo-active in PD. This region showed significantly increased activity during ET movements in patients off medication. Levodopa had no effect on this discrepancy. Our results suggest that dopamine replacement therapy has a non-task-specific effect on motor corticostriatal regions, and support the hypothesis that increases and decreases in cortical activity in PD are related to the mesocortical dopamine pathway imbalance. PMID- 22304629 TI - Salmonella Enteritidis strains from poultry exhibit differential responses to acid stress, oxidative stress, and survival in the egg albumen. AB - Salmonella Enteritidis is the major foodborne pathogen that is primarily transmitted by contaminated chicken meat and eggs. We recently demonstrated that Salmonella Enteritidis strains from poultry differ in their ability to invade human intestinal cells and cause disease in orally challenged mice. Here we hypothesized that the differential virulence of Salmonella Enteritidis strains is due to the differential fitness in the adverse environments that may be encountered during infection in the host. The responses of a panel of six Salmonella Enteritidis strains to acid stress, oxidative stress, survival in egg albumen, and the ability to cause infection in chickens were analyzed. This analysis allowed classification of strains into two categories, stress-sensitive and stress-resistant, with the former showing significantly (p<0.05) reduced survival in acidic (gastric phase of infection) and oxidative (intestinal and systemic phase of infection) stress. Stress-sensitive strains also showed impaired intestinal colonization and systemic dissemination in orally inoculated chickens and failed to survive/grow in egg albumen. Comparative genomic hybridization microarray analysis revealed no differences at the discriminatory level of the whole gene content between stress-sensitive and stress-resistant strains. However, sequencing of rpoS, a stress-regulatory gene, revealed that one of the three stress-sensitive strains carried an insertion mutation in the rpoS resulting in truncation of sigma(S). Finding that one of the stress-sensitive strains carried an easily identifiable small polymorphism within a stress response gene suggests that the other strains may also have small polymorphisms elsewhere in the genome, which likely impact regulation of stress or virulence associated genes in some manner. PMID- 22304630 TI - Isolation and molecular characterization of Escherichia coli O157 from broiler and human samples. AB - There is a lack of information about the role of poultry, specifically chicken, in transmission of Escherichia coli (E. coli) O157 and subsequent human illnesses. This study was therefore aimed at investigating the presence of E. coli O157 and its virulence genes in various samples collected from broiler chickens and humans in Eastern Turkey by culture, immunomagnetic separation (IMS), and polymerase chain reaction (PCR). The genetic relationship between broiler and human isolates was also examined by pulsed-field gel electrophoresis (PFGE). In the PCR analysis of sorbitol-negative isolates, E. coli O157 was identified in 0.1% (1/1000) and 0.4% (4/1000) of the liver and cecum samples of broiler chickens, respectively. On the other hand, none of the carcass samples were determined to be positive for E. coli O157. Overall, the results indicated that 12% (3/25) of the flocks were positive for E. coli O157. The differences between the flocks in terms of the positivity were determined to be statistically significant (p<0.001). Ten (2.7%) of 367 human stool samples were also positive for E. coli O157 in the PCR examination. None of the broiler and human E. coli O157 isolates possessed H7, shigatoxins 1-2, or enterohemolysin genes, whereas all the broiler isolates and one of the human isolates were positive for intimin gene. In the PFGE analysis, a total of eight different profiles (four from broiler and four from human isolates) were observed. However, there were no genetic relationships between broiler and human E. coli O157 isolates. It can be concluded that more detailed studies are needed in poultry to better understand the role of these species in the epidemiology of E. coli 0157 infections in humans. PMID- 22304632 TI - Distribution profiles of chloroform, weak organic acids, and PCBs on granular activated carbon columns from Waterford, New York. PMID- 22304631 TI - Dephosphorylation of the core clock protein KaiC in the cyanobacterial KaiABC circadian oscillator proceeds via an ATP synthase mechanism. AB - The circadian clock of the cyanobacterium Synechococcus elongatus can be reconstituted in vitro from three proteins, KaiA, KaiB, and KaiC in the presence of ATP, to tick in a temperature-compensated manner. KaiC, the central cog of this oscillator, forms a homohexamer with 12 ATP molecules bound between its N- and C-terminal domains and exhibits unusual properties. Both the N-terminal (CI) and C-terminal (CII) domains harbor ATPase activity, and the subunit interfaces between CII domains are the sites of autokinase and autophosphatase activities. Hydrolysis of ATP correlates with phosphorylation at threonine and serine sites across subunits in an orchestrated manner, such that first T432 and then S431 are phosphorylated, followed by dephosphorylation of these residues in the same order. Although structural work has provided insight into the mechanisms of ATPase and kinase, the location and mechanism of the phosphatase have remained enigmatic. From the available experimental data based on a range of approaches, including KaiC crystal structures and small-angle X-ray scattering models, metal ion dependence, site-directed mutagenesis (i.e., E318, the general base), and measurements of the associated clock periods, phosphorylation patterns, and dephosphorylation courses as well as a lack of sequence motifs in KaiC that are typically associated with known phosphatases, we hypothesized that KaiCII makes use of the same active site for phosphorylation and dephosphorlyation. We observed that wild-type KaiC (wt-KaiC) exhibits an ATP synthase activity that is significantly reduced in the T432A/S431A mutant. We interpret the first observation as evidence that KaiCII is a phosphotransferase instead of a phosphatase and the second that the enzyme is capable of generating ATP, both from ADP and P(i) (in a reversal of the ATPase reaction) and from ADP and P T432/P-S431 (dephosphorylation). This new concept regarding the mechanism of dephosphorylation is also supported by the strikingly similar makeups of the active sites at the interfaces between alpha/beta heterodimers of F1-ATPase and between monomeric subunits in the KaiCII hexamer. Several KaiCII residues play a critical role in the relative activities of kinase and ATP synthase, among them R385, which stabilizes the compact form and helps kinase action reach a plateau, and T426, a short-lived phosphorylation site that promotes and affects the order of dephosphorylation. PMID- 22304633 TI - Mobility in soil and plant availability of metals derived from incinerated municipal refuse. PMID- 22304634 TI - 1-Nitropyrene concentration and bacterial mutagenicity in on-road vehicle particulate emissions. PMID- 22304635 TI - Reaction pathways of trihalomethane formation from the halogenation of dihydroxyaromatic model compounds for humic acid. PMID- 22304636 TI - Mass transfer coefficient correlations for volatilization of organic solutes from water. PMID- 22304637 TI - Chemical changes in concentrated, acidic, metal-bearing wastewaters when treated with lime. PMID- 22304638 TI - Photochemical ozone formation in urban and point source plumes. PMID- 22304639 TI - Partition equilibriums of nonionic organic compounds between soil organic matter and water. PMID- 22304640 TI - Partitioning of strontium-90 among aqueous and mineral species in a contaminated aquifer. PMID- 22304641 TI - Effect of natural organic coatings on the coagulation of particles. PMID- 22304642 TI - Notes. Reductive destruction of hydrazines as an approach to hazard control. PMID- 22304643 TI - Notes. Impact of fossil fuel combustion on sediments of Lake Michigan: a reprise. PMID- 22304644 TI - Notes. Electrolytic preparation of [36Cl]chlorine dioxide from hydrochloric acid chlorine-36. PMID- 22304645 TI - Notes. Application of .gamma.-.gamma.-directional correlation measurements for speciation studies in environmental research. PMID- 22304647 TI - Proteomic profiling of the coagulation of milk proteins induced by chymosin. AB - Chymosin-induced coagulation of individual milk proteins during incubation at 30 degrees C was investigated using a proteomic approach. The addition of chymosin (0.006 units/mL) caused the milk proteins to coagulate after a 3 h incubation period. Approximately 88% of the milk proteins were coagulated into the milk pellet fraction, and the protein concentration of the milk supernatant fraction (MSF) decreased from 29.88 +/- 0.12 to 3.74 +/- 0.13 mg/mL. SDS-PAGE analysis showed that alpha(S)-, beta- and kappa-caseins in the MSF were almost depleted and that the total intensity of the protein bands corresponding to alpha(S) caseins (alpha(S1) and alpha(S2)), beta-casein, and kappa-casein decreased from 1088.0, 901.5, and 617.0 area units to 6.9, 6.1, and 5.2 area units, respectively. Two-dimensional electrophoresis analysis indicated that alpha(S1)-, alpha(S2)-, beta-, and kappa-casein and a fraction of the beta-lactoglobulin and serum albumin were found in the MSF following incubation with chymosin. PMID- 22304648 TI - Nitroso-redox status and vascular function in marginal and severe ascorbate deficiency. AB - Marginal vitamin C (ascorbic acid) deficiency is a prevalent yet underappreciated risk factor for cardiovascular disease. Along with glutathione, ascorbate plays important roles in antioxidant defense and redox signaling. Production of nitric oxide (NO) and reactive oxygen species and their interaction, giving rise to nitroso and nitrosyl product formation, are key components of the redox regulation/signaling network. Numerous in vitro studies have demonstrated that these systems are interconnected via multiple chemical transformation reactions, but little is known about their dynamics and significance in vivo. AIMS: We sought to investigate the time-course of changes in NO/redox status and vascular function during ascorbate depletion in rats unable to synthesize vitamin C. RESULTS: We here show that both redox and protein nitros(yl)ation status in blood and vital organs vary dynamically during development of ascorbate deficiency. Prolonged marginal ascorbate deficiency is associated with cell/tissue-specific perturbations in ascorbate and glutathione redox and NO status. Scurvy develops earlier in marginally deficient compared to adequately supplemented animals, with blunted compensatory NO production and a dissociation of biochemistry from clinical symptomology in the former. Paradoxically, aortic endothelial reactivity is enhanced rather than impaired, irrespective of ascorbate status. Innovation/Conclusion: Enhanced NO production and protein nitros(yl)ation are integral responses to the redox stress of acute ascorbate deprivation. The elevated cardiovascular risk in marginal ascorbate deficiency is likely to be associated with perturbations of NO/redox-sensitive signaling nodes unrelated to the regulation of vascular tone. This new model may have merit for the future study of redox-sensitive events in marginal ascorbate deficiency. PMID- 22304649 TI - Functional characterization of genetic polymorphisms identified in the promoter region of the bovine PEPS gene. AB - Peptidase S (PEPS) is a metallopeptidase that cleaves N-terminal residues from proteins and peptides. PEPS is used as a cell maintenance enzyme with critical roles in peptide turnover. The promoter region located upstream of the initiation site plays an important role in regulating gene expression. Polymorphism in the promoter region can alter gene expression and lead to biological changes. In the current study, polymorphisms in the promoter region of the PEPS gene were investigated. Polymerase chain reaction (PCR)-restriction fragment length polymorphism and DNA sequencing methods were used to screen sequence variations in the promoter region of DNA samples from 743 Chinese Holstein cattle. Two polymorphisms (g. -534 T>C and g. -2545 G>A) were identified and eight haplotypes were classified by haplotype analysis. The two genetic polymorphisms and haplotypes were associated with fat percentage and somatic cell score in Chinese Holstein cattle. The results of real-time PCR showed that cow kidneys exhibit the highest PEPS expression level. Moreover, bioinformatics analysis predicted that the single-nucleotide polymorphism g. -534 T>C is located in the core promoter region and in the transcription factor binding sites. The promoter activities of the polymorphism of -543 T>C were measured by luciferase assay in the human kidney epithelial cell line 293T. Transcriptional activity is significantly lower in cell lines transfected with the reporter construct containing 2.5 kb upstream fragments with -543 C than in those with wild-type -543 T. The results indicated that genetic variation at locus -543 influences PEPS promoter activity. The genetic variation in the promoter region of PEPS gene may regulate PEPS gene transcription and might have consequences at a regulatory level. PMID- 22304650 TI - Novel mass spectrometric method for phosphorylation quantification using cerium oxide nanoparticles and tandem mass tags. AB - The stoichiometry of protein phosphorylation significantly impacts protein function. The development of quantitative techniques in mass spectrometry has generated the ability to systematically monitor the regulation levels of various proteins. This study reports an integrated methodology using cerium oxide nanoparticles and isobaric tandem mass tag (TMT) labeling to assess absolute stoichiometries of protein phosphorylation. This protocol was designed to directly measure the dephosphorylation levels for a known phosphorylation site, therefore allowing for quantification of phosphosites. Both the accuracy and precision of the method were verified using standard peptides and protein tryptic digests. This novel method was then applied to quantify phosphorylations on eukaryotic initiation factor 3H (eIF3H), a protein integral to overall eukaryotic protein translation initiation. To date, this is the first report of assessment of protein phosphorylation quantification on eIF3. PMID- 22304651 TI - Increased serum activin-A differentiates alcoholic from cirrhosis of other aetiologies. AB - BACKGROUND: Activin-A is a molecule of the TGF superfamily, implicated in liver fibrosis, regeneration and stem cell differentiation. However, data on activins in liver diseases are few. We therefore studied serum levels of activin-A in chronic liver diseases. To identify the origin of activin-A, levels in the hepatic vein were also estimated. MATERIALS AND METHODS: Nineteen controls and 162 patients participated in the study: 39 with hepatocellular carcinoma (HCC: 19 viral associated and 20 alcohol associated), 18 with chronic hepatitis C (CHC), 47 with primary biliary cirrhosis (26 PBC stage I-II and 21 stage IV), 22 with alcoholic cirrhosis (AC, hepatic vein blood available in 16), 20 with HCV cirrhosis (hepatic vein blood available in 18) and 16 patients with alcoholic fatty liver with mild to moderate fibrosis but no cirrhosis. RESULTS: Activin-A levels were significantly increased (P < 0.001) in serum of patients with AC (median 673 pg/mL, range 449-3279), compared with either controls (149 pg/mL, 91 193) or patients with viral cirrhosis (189 pg/mL, 81-480), CHC (142 pg/mL, 65 559) PBC stage I-II (100 pg/mL, 59-597) and PBC stage IV (104 pg/mL, 81-579). Only patients with AC-associated HCC had significantly increased levels of activin-A (2403 pg/mL, 1561-7220 pg/mL). Activin-A serum levels could accurately discriminate AC from cirrhosis of other aetiologies and noncirrhotic alcoholic fatty liver with fibrosis. CONCLUSIONS: Increased serum levels of activin-A only in patients with alcohol-related cirrhosis or HCC suggest a possible role of this molecule in the pathophysiology of AC. Further research is warranted to elucidate its role during the profibrotic process and its possible clinical applications. PMID- 22304652 TI - What is your diagnosis? CBC and cytogram data from a Sprague-Dawley rat. PMID- 22304653 TI - Pallambins A and B, unprecedented hexacyclic 19-nor-secolabdane diterpenoids from the Chinese liverwort Pallavicinia ambigua. AB - Pallambins A (1) and B (2), two novel 19-nor-7,8-secolabdane diterpenoids with unprecedented tetracyclo[4.4.0(3,5).0(2,8)]decane skeletons, along with a pair of structurally related isomers, pallambins C (3) and D (4), were isolated from the Chinese liverwort Pallavicinia ambigua. Their structures with absolute configurations were determined by means of NMR, X-ray diffraction, and CD analyses. Their preliminary cytotoxicity to human cancer cells was also tested. PMID- 22304654 TI - Integrating spiritual care within palliative care: an overview of nine demonstration projects. PMID- 22304655 TI - Evaluation of the sterility testing process of hematopoietic stem cells at Canadian Blood Services. AB - BACKGROUND: Sterility testing of hematopoietic stem cells (HSCs) at The Canadian Blood Services Stem Cell Laboratory is performed using BacT/ALERT aerobic (SA) culture bottles. This study was conducted to verify the efficacy of this method and to assess the use of the BacT/ALERT aerobic (BPA) and anaerobic (BPN) culture bottles for microbial testing of HSCs. STUDY DESIGN AND METHODS: HSC products, including cryopreserved apheresis peripheral blood, marrow, and cord blood and fresh cord blood, were spiked with four aerobic organisms including Staphylococcus epidermidis, Bacillus cereus, Pseudomonas aeruginosa, and Candida albicans, and the anaerobe Bacteroides fragilis at a target concentration of 100 colony-forming units (CFUs)/mL. One to 2 mL of pre- and postspiked samples was inoculated into SA, BPA, and BPN bottles in duplicate and incubated for 5 to 10 days. The presence of the testing organisms in positive culture bottles was confirmed by plating on blood agar. RESULTS: The BacT/ALERT system detected the aerobic organisms in all HSCs in SA and BPA bottles within 34.1 hours while B. fragilis was detected only in BPN bottles within 68.6 hours. The mean recovered concentration of microorganisms in the HSC products ranged from 55 to 352 CFUs/mL with the exception of B. cereus, which was greater than 10(3) CFUs/mL. CONCLUSION: This study shows that the current sterility testing process at the Canadian Blood Services Stem Cell Laboratory detected the tested aerobic but not the anaerobic microbial contaminants in HSCs. The ability of the BacT/ALERT system using BPA and BPN bottles to detect bacterial contamination in HSCs was also demonstrated. PMID- 22304656 TI - Is the occurrence of the sticking region the result of diminishing potentiation in bench press? AB - In this study we investigated if the occurrence of the sticking region was a result of diminishing potentiation (coinciding delayed muscle activation) or the result of a mechanically poor region in which the muscles can produce less force. A regular one-repetition maximum (1RM) free-weight bench press was compared with isometric bench presses performed at 12 different positions. A lower force at the sticking region compared to the other regions in the isometric bench presses would confirm the mechanically-poor-position hypothesis. Twelve resistance trained males (age 21.7 +/- 1.3 years, mass 78 +/- 5.8 kg, height 1.81 +/- 0.05 m) were tested in 1RM and in isometric contractions in bench press in 12 different positions, indicated by the vertical distance between barbell and sternum, covering the whole range of motion during the concentric phase. Barbell kinematics and muscle activity were registered. In both types of executions a region of lower force output was observed, which supports the mechanically-poor position hypothesis. Electromyographic activity of four muscles showed the same pattern in the isometric and 1RM attempts. It was concluded that diminishing effect potentiation could not explain the existence of the sticking region. PMID- 22304657 TI - Decision maker priorities for providing antiretroviral therapy in HIV-infected South Africans: a qualitative assessment. AB - In resource-limited settings, successful HIV treatment scale-up has been tempered by reports of funding shortfalls. We aimed to determine the priorities, including ethical considerations, of decision makers for HIV antiretroviral programs. We conducted qualitative interviews with 12 decision makers, identified using purposive sampling. Respondents engaged in one-on-one, semi-structured interviews. We developed an interview guide to direct questions about key priorities and motivations for decision making about HIV antiretroviral programs. We evaluated textual data from the interviews to identify themes. Among 12 respondents, 10 (83%) lived and worked in South Africa. Respondents came from Western Cape, Gauteng, and KwaZulu-Natal provinces and worked primarily in urban settings. The respondents supported prioritizing individual patients based on treatment adherence, pregnancy status to prevent maternal-to-child HIV transmission and/or orphans, and severity of illness. However, priorities based on severity of illness varied, with first-come/first-serve, prioritization of the most severely ill, and prioritization of the least severely ill discussed. Respondents opposed prioritizing based on patient socioeconomic characteristics. Other priorities included the number of persons receiving treatment; how treated patients are distributed in the population (e.g., urban/rural); and treatment policy (e.g., number of antiretroviral regimens). Motivations included humanitarian concerns; personal responsibility for individual patients; and clinical outcomes (e.g., patient-level morbidity/mortality, saving lives) and/or social outcomes (e.g., restoring patients as functional family members). Decision makers have a wide range of priorities for antiretroviral provision in South Africa, and the motivations underlying these priorities suggest at times conflicting ethical considerations for providing HIV treatment when resources are limited. PMID- 22304658 TI - Modulation of somatosensory profiles by spinal cord stimulation in primary Raynaud's syndrome. AB - BACKGROUND AND GOAL: Spinal cord stimulation (SCS) is an effective antinociceptive treatment for various neuropathic pain syndromes. Apart from antinociceptive action, it may modulate overall somatosensory perception. This case report targets the question of whether SCS may alter quantitative sensory testing (QST) in a patient with primary Raynaud's syndrome. MATERIALS AND METHODS: We report on a 44-year-old female patient with primary Raynaud's syndrome who had SCS via cervical and lumbar electrodes. QST was performed in a standardized manner assessing cold detection threshold (CDT) and warm detection threshold (WDT), cold pain threshold (CPT) and heat pain threshold (HPT), mechanical detection threshold (MDT) and mechanical pain threshold (MPT) thresholds, and vibration detection threshold (VDT) and pressure pain thresholds (PPT). We tested at the dorsum of the right/left hand of the patient with engaged and disengaged SCS. Test results were compared with a control group of 80 subjects. RESULTS: Without SCS, the patient showed a sensory decrease in CDT, MDT, MPT, and VDT. SCS influenced the perception of cold, warm, and tactile detection thresholds, whereby CDT, WDT, and VDT were impaired and MDT was improved. CONCLUSION: SCS significantly modulated the somatosensory profile in a patient with primary Raynaud's syndrome. These effects were pronounced in qualities involving Abeta, C, and A? nerve fibers. Further investigations may help to understand the mechanisms of action of SCS. PMID- 22304659 TI - Fast and pH-dependent release of domperidone from orally disintegrating tablets. AB - There has been growing interest in orally disintegrating tablets (ODTs) during the last decade due to their better patient acceptance and compliance. Further, drug dissolution and absorption may be significantly improved. This work describes the preparation of fast and pH-dependent release ODTs for domperidone by direct compression using crospovidone as superdisintegrant. Solid dispersions of domperidone and Eudragit L100-55, at different weight ratios, were prepared and characterized by DSC, TGA, X-ray diffraction, and FTIR, which indicated the presence of drug-polymer interaction. Disintegration time, friability, and hardness of ODTs were evaluated. In vitro drug release in 0.1N HCl and in phosphate buffer (pH 5.8 and 6.8) was investigated. All domperidone ODTs had fast disintegration times (6 KP) and acceptable friability (<1%). Drug release from fast release ODTs was highly improved; reaching 97% after 10 min in 0.1N HCl, compared to the dissolution of the free drug. Drug release from solid dispersions was pH dependent; showing higher release rates at pH 6.8 than at lower pH values. The controlled-release ODT resulted in 47% drug release in 0.1N HCl, with the rest of drug released at pH 6.8. Domperidone ODTs were considered suitable for ODT formulation. PMID- 22304661 TI - Flibanserin and 8-OH-DPAT implicate serotonin in association between female marmoset monkey sexual behavior and changes in pair-bond quality. AB - INTRODUCTION: Psychopathological origins of personally distressing, hypoactive sexual desire disorder (HSDD) in women are unknown, but are generally attributed to an inhibitory neural regulator, serotonin (5-HT). Flibanserin, a 5-HT(1A) agonist and 5-HT(2A) antagonist, shows promise as a treatment for HSDD. AIM: To test the hypothesis that female marmoset sexual behavior is enhanced by flibanserin and diminished by 8-OH-DPAT, in order to evaluate the efficacy of serotonergic modulation of female sexual behavior in a pairmate social setting comparable to humans. METHODS: Sexual and social behavior were examined in eight female marmoset monkeys receiving daily flibanserin (15 mg/kg), 8-OH-DPAT (0.1 mg/kg), or corresponding vehicle for 15-16 weeks in a counterbalanced, within subject design, while housed in long-term, stable male-female pairs. MAIN OUTCOME MEASURES: Marmoset pairmate interactions, including sexual and social behavior, were scored during weeks 5-6 of daily flibanserin, 8-OH-DPAT or vehicle treatment. 24-hour pharmacokinetic profiles of the drugs and their metabolites, as well as drug-induced acute symptoms of the 5-HT behavioral syndrome were also assessed. RESULTS: Two-way analysis of variance reveals that flibanserin-treated females attract more male sexual interest (P=0.020) and trigger increased grooming (P=0.001) between partners. In contrast, 8-OH-DPAT-treated females show increased rejection of male sexual advances (P=0.024), a tendency for decreased male sexual interest (P=0.080), and increased aggression with their male pairmates (P=0.049). CONCLUSIONS: While 8-OH-DPAT-treated female marmosets display decreased sexual receptivity and increased aggressive interactions with their male pairmates, flibanserin-treated female marmosets demonstrate increased affiliative behavior with their male pairmates. Such pro-affiliation attributes may underlie flibanserin's effectiveness in treating HSDD in women. PMID- 22304662 TI - Effects of DNA binding of the zinc finger and linkers for domain fusion on the catalytic activity of sequence-specific chimeric recombinases determined by a facile fluorescent system. AB - Artificial zinc finger proteins (ZFPs) consist of Cys(2)-His(2)-type modules composed of ~30 amino acids with a betabetaalpha structure that coordinates a zinc ion. ZFPs that recognize specific DNA target sequences can substitute for the binding domains of enzymes that act on DNA to create designer enzymes with programmable sequence specificity. The most studied of these engineered enzymes are zinc finger nucleases (ZFNs). ZFNs have been widely used to model organisms and are currently in human clinical trials with an aim of therapeutic gene editing. Difficulties with ZFNs arise from unpredictable mutations caused by nonhomologous end joining and off-target DNA cleavage and mutagenesis. A more recent strategy that aims to address the shortcomings of ZFNs involves zinc finger recombinases (ZFRs). A thorough understanding of ZFRs and methods for their modification promises powerful new tools for gene manipulation in model organisms as well as in gene therapy. In an effort to design efficient and specific ZFRs, the effects of the DNA binding affinity of the zinc finger domains and the linker sequence between ZFPs and recombinase catalytic domains have been assessed. A plasmid system containing ZFR target sites was constructed for evaluation of catalytic activities of ZFRs with variable linker lengths and numbers of zinc finger modules. Recombination efficiencies were evaluated by restriction enzyme analysis of isolated plasmids after reaction in Escherichia coli and changes in EGFP fluorescence in mammalian cells. The results provide information relevant to the design of ZFRs that will be useful for sequence specific genome modification. PMID- 22304663 TI - High plasma level of long Pentraxin 3 is associated with insulin resistance in women with polycystic ovary syndrome. AB - OBJECTIVES: Polycystic ovary syndrome (PCOS) is characterized by insulin resistance. Chronic low-grade inflammation has been anticipated to play role in the pathogenesis of both insulin resistance and atherosclerosis. Pentraxin 3 (PTX3) is an inflammatory mediator synthesized in a variety of cells and tissues including heart, vascular endothelial cells, macrophages and adipocytes. In the present study, serum PTX3 level and its relationship with insulin resistance were investigated in patients with PCOS. MATERIALS AND METHODS: Forty patients with PCOS and 40 age- and body mass index (BMI)-matched healthy controls were enrolled in the study. PTX3 and high-sensitivity C-reactive protein (hs-CRP) levels were determined by enzyme immunoassay (EIA). Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula. RESULTS: Plasma levels of PTX3, hs-CRP and HOMA-IR scores were all significantly higher (p = 0.021, p = 0.002 and p = 0.0001, respectively) in women with PCOS compared with healthy controls. Blood PTX3 level correlated positively with hs-CRP, BMI, waist to-hip ratio (WHR), HOMA-IR and negatively with high-density lipoprotein cholesterol level (p < 0.05, for all). After adjustment for age and BMI, PTX3, total testosterone levels and BMI remained as independent predictors of HOMA-IR scores (p < 0.05, for all). CONCLUSION: PTX3 level is increased in patients with PCOS in concordance with insulin resistance. PMID- 22304664 TI - Dendritic calcium mechanisms and long-term potentiation in cortical inhibitory interneurons. AB - Calcium (Ca(2+) ) is a major second messenger in the regulation of different forms of synaptic and intrinsic plasticity. Tightly organized in space and time, postsynaptic Ca(2+) transients trigger the activation of many distinct Ca(2+) signaling cascades, providing a means for a highly specific signal transduction and plasticity induction. High-resolution two-photon microscopy combined with highly sensitive synthetic Ca(2+) indicators in brain slices allowed for the quantification and analysis of postsynaptic Ca(2+) dynamics in great detail. Much of our current knowledge about postsynaptic Ca(2+) mechanisms is derived from studying Ca(2+) transients in the dendrites and spines of pyramidal neurons. However, postsynaptic Ca(2+) dynamics differ considerably among different cell types. In particular, distinct rules of postsynaptic Ca(2+) signaling and, accordingly, of Ca(2+) -dependent plasticity operate in GABAergic interneurons. Here, I review recent progress in understanding the complex organization of postsynaptic Ca(2+) signaling and its relevance to several forms of long-term potentiation at excitatory synapses in cortical GABAergic interneurons. PMID- 22304665 TI - Role of lipid oxidation, chelating agents, and antioxidants in metallic flavor development in the oral cavity. AB - This study investigated the production of metallic flavor, which is a combination of taste and retronasal odor. Chemical reactions in the oral cavity and saliva of healthy subjects were investigated after ingesting iron and copper solutions above and near threshold levels. Significant increase in lipid oxidation (p < 0.001) occurred after metal ingestion, detected as TBARS values. Ferrous ion caused the greatest flavor sensation and lipid oxidation, followed by cupric and cuprous ions. Ferric ion did not cause metallic sensation. Occurrence of oxidation was supported by damage to salivary proteins, detected as protein carbonyls, and by a significant increase of odorous lipid oxidation related aldehydes. Sensory evaluation demonstrated that antioxidants (vitamins E and C) minimally reduced metallic flavor but that chelating agents (EDTA and lactoferrin) removed the metallic flavor. The role of lipid oxidation is essential for the production of a metallic flavor from ingestion of ferrous, cupric, and cuprous ions. PMID- 22304666 TI - Sequence context effect on strand slippage in natural DNA primer-templates. AB - Strand slippage has been found to occur in primer-templates containing a templating thymine, cytosine, and guanine, leading to the formation of misaligned structures with a single-nucleotide bulge. If remained in the active site of low fidelity polymerases during DNA replication, these misaligned structures can ultimately bring about deletion mutations. In this study, we performed NMR investigations on primer-template models containing a templating adenine. Similar to our previous results on guanine, adenine templates are also less prone to strand slippage than pyrimidine templates. Misalignment occurs only in primer templates that form a terminal C.G or G.C base pair. Together with our previous findings on thymine, cytosine, and guanine templates, the present study reveals strand slippage can occur in any kind of natural templating bases during DNA replication, providing insights into the origin of mutation hotspots in natural DNA sequences. In addition to the type of incoming base upon misincorporation, the propensity of strand slippage in primer-templates depends also on the type of templating base, its upstream and downstream bases. PMID- 22304667 TI - Improved resolution of hydrocarbon structures and constitutional isomers in complex mixtures using gas chromatography-vacuum ultraviolet-mass spectrometry. AB - Understanding the composition of complex hydrocarbon mixtures is important for environmental studies in a variety of fields, but many prevalent compounds cannot be confidently identified using traditional gas chromatography/mass spectrometry (GC/MS) techniques. This work uses vacuum-ultraviolet (VUV) ionization to elucidate the structures of a traditionally "unresolved complex mixture" by separating components by GC retention time, t(R), and mass-to-charge ratio, m/z, which are used to determine carbon number, N(C), and the number of rings and double bonds, N(DBE). Constitutional isomers are resolved on the basis of t(R), enabling the most complete quantitative analysis to date of structural isomers in an environmentally relevant hydrocarbon mixture. Unknown compounds are classified in this work by carbon number, degree of saturation, presence of rings, and degree of branching, providing structural constraints. The capabilities of this analysis are explored using diesel fuel, in which constitutional isomer distribution patterns are shown to be reproducible between carbon numbers and follow predictable rules. Nearly half of the aliphatic hydrocarbon mass is shown to be branched, suggesting branching is more important in diesel fuel than previously shown. The classification of unknown hydrocarbons and the resolution of constitutional isomers significantly improves resolution capabilities for any complex hydrocarbon mixture. PMID- 22304668 TI - Improving rates of herpes zoster vaccination with a clinical decision support system in a primary care practice. AB - RATIONALE: Herpes zoster (shingles) is a localized neurocutaneous eruption of blisters caused by reactivation of the varicella zoster virus. The cost of care for herpes zoster and its complications is estimated at $1.1 billion. The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommends a one-time dose of the vaccine for adults aged 60 years or older. Despite that recommendation, utilization of the vaccine is very low. One way to boost the delivery of preventive services such as vaccinations is with a computerized clinical decision support system. Our study found that the herpes zoster vaccination rate increased significantly after the implementation of such a system. AIMS: To study utilization of herpes zoster vaccine before and after the implementation of a web-based clinical decision support software solution in a primary care practice. METHODS: Billing data was utilized to determine number of herpes zoster vaccination administered to patients for a 12-month period during the implementation of the software solution. RESULTS: The utilization of vaccinations improved from 63 to 117 (53.8% increase) for one primary care practice and from 54 to 127 (42.5% increase) in the other primary care practice. CONCLUSION: Herpes zoster vaccination rate significantly improved with implementation of a web-based clinical decision support system. PMID- 22304669 TI - Accurate rate constants for decomposition of aqueous nitrous acid. AB - Decomposition of nitrous acid in aqueous solution has been studied by stopped flow spectrophotometry to resolve discrepancies in literature values for the rate constants of the decomposition reactions. Under the conditions employed, the rate limiting reaction step comprises the hydrolysis of NO(2). A simplified rate law based on the known elementary reaction mechanism provides an excellent fit to the experimental data. The rate constant, 1.34 * 10(-6) M(-1) s(-1), is thought to be of higher accuracy than those in the literature as it does not depend on the rate of parallel reaction pathways or on the rate of interphase mass transfer of gaseous reaction products. The activation energy for the simplified rate law was established to be 107 kJ mol(-1). Quantum chemistry calculations indicate that the majority of the large activation energy results from the endothermic nature of the equilibrium 2HNO(2) ? NO + NO(2) + H(2)O. The rate constant for the reaction between nitrate ions and nitrous acid, which inhibits HNO(2) decomposition, was also determined. PMID- 22304670 TI - Metal ions in cause, progression, treatment and diagnosis of genetic disorders, metabolic diseases and cancer. PMID- 22304671 TI - Construction of aromatic [5,5] spiroketals via hypoiodite-catalyzed etherification combined in relay cascades. AB - An approach is developed for the synthesis of bisbenzannelated spiro[5,5]ketals via a catalytic relay reaction cascade involving a new cyclo-etherification, which is prompted by fluoride and catalyzed by the hypoiodite species generated in situ from irradiative aerobic oxidation of an iodide ion formed in the former step of the reaction cascade. PMID- 22304672 TI - Tactile function in children with unilateral cerebral palsy compared to typically developing children. AB - PURPOSE: Tactile deficits have been understudied in children with unilateral cerebral palsy (UCP) using a limited range of tactile assessments. This study aims to characterize performance across a comprehensive battery of tactile registration and perception assessments in children with UCP and typically developing children (TDC). METHODS: Fifty-two children with UCP (Gross Motor Function Classification System I = 34, II = 18; Manual Ability Classification System I = 36, II = 16) and 34 TDC were assessed using Semmes Weinstein Monofilaments (tactile registration), and single-point localization, double simultaneous, static and moving two-point discrimination, stereognosis, and texture perception (tactile perception). RESULTS: Children with UCP performed consistently worse with their impaired hand than their unimpaired hand (Z = 2.77 5.61; p < 0.005). Both hands of children with UCP performed worse than either hand of TDC (Z = -2.08 to 5.23; p = 0.037-< 0.001). Forty percent of children with UCP had tactile registration and perception deficits, 37% had perception deficits only and 23% had no tactile deficit. The larger the tactile registration deficit, the poorer the performance on all tactile perceptual tests (r = 0.568 0.670; p < 0.001). CONCLUSIONS: Most children with UCP demonstrate poor tactile perception and over one-third also demonstrate poor tactile registration. We contend that tactile dysfunction may contribute to functional impairment and is a possible target for intervention. [ IMPLICATIONS FOR REHABILITATION: * Cerebral palsy (CP) is the most prevalent physical disability in childhood, with an incidence of approximately 2 cases per 1000 live births; about 35% of children with CP have unilateral cerebral palsy (UCP).* Assessment and treatment has been focused on the motor impairment; however, it is known that children with UCP are also likely to have sensory impairment.* Understanding the nature and severity of sensory, specifically tactile, impairment in children with UCP will assist therapists to direct treatment accordingly and possibly impact the motor impairment.] PMID- 22304673 TI - Reactive oxygen species: the achilles' heel of cancer cells? AB - Cancer development, progression, and metastasis are multistep processes. Accumulating evidence suggests that reactive oxygen species (ROS) are critically involved in cancer cell functions. This Forum reviews our current understanding of the important and paradoxical role of ROS in the regulation of tumor associated cell properties, genes, and signaling pathways. The six reviews in this Forum showcase the up-to-date knowledge on how ROS modulate or interact with the p53 protein, epithelial-mesenchymal transition, tumor stromal cells, angiogenesis, and cancer stem cells, which are essential factors in cancer development and metastasis. The contributions demonstrate that ROS levels in cancer cells are tightly controlled, which brings promises and challenges in the development of novel ROS-targeted anticancer therapies. Further understanding of the biological mechanisms underlying the effects of oxidative stress on tumor growth and metastasis will contribute to the advancement of cancer biology and cancer treatment. PMID- 22304674 TI - Immunohistochemical expression of somatostatin receptor subtypes 2 and 5 in colorectal cancer. AB - BACKGROUND: To determine the immunohistochemical expression levels of the somatostatin receptor subtypes 2 and 5 (Sst2 and Sst5) in patients with colorectal cancer (CRC) and to investigate the association of Sst2 and Sst5 expression with clinicopathological parameters. MATERIALS AND METHODS: A retrospective analysis of formalin-fixed and paraffin-embedded CRC surgical specimens from 81 patients assessed by immunohistochemistry for Sst2 and Sst5 expression. RESULTS: Sst2 and Sst5 expression levels showed significant, negative association with CRC invasion and liver metastasis (P values < 0.05) while Sst2 also showed significantly increased expression in lower-grade tumours as well as in tumours located in the rectum (P values < 0.05). Patients with CRC expressing either Sst2 or Sst5 had significantly longer survival rates (P values < 0.05), although Sst expression was not found to be an independent predictor of survival after controlling for other known prognostic clinicopathological variables (P values > 0.05). CONCLUSIONS: The present data confirm the relationship of Sst2 and Sst5 expression levels with reduced tumour aggressiveness. PMID- 22304676 TI - A self-help behavioral activation treatment for geriatric depressive symptoms. AB - This study investigated behavioral activation (BA) bibliotherapy as a treatment for late-life depressive symptoms. BA bibliotherapy was administered using Addis and Martell's Overcoming depression one step at a time as a stand-alone treatment that was completed by participants (N=26) over a 4-week period [Addis, M.E., & Martell, C.R. (2004). Overcoming depression one step at a time. Oakland, CA: New Harbinger Publications, Inc.]. Results of an immediate intervention group were compared with those of a delayed treatment control group and treatment response for both groups was evaluated at 1-month follow-up. Primary outcome results showed that symptoms on a clinician-rated measure of depressive symptoms, Hamilton Rating Scale for Depression, were significantly lower at post-treatment for those who received immediate BA bibliotherapy compared with those who were in the delayed treatment control condition. However, self-reported depressive symptoms (a secondary outcome measured via the Geriatric Depression Scale), were not significantly different at this period. Because study control was lost after the delayed treatment group received the intervention, within-subjects analyses examining both treatment groups combined showed that clinician-rated depressive symptoms significantly decreased from pre-treatment to both post-treatment and 1 month follow-up. Self-reported depressive symptoms were significantly lower from pre-treatment to 1-month follow-up. These findings suggest that BA may be useful in treating mild or subthreshold depressive symptoms in an older adult population. PMID- 22304677 TI - Detection of Fusobacterium nucleatum in chorionic tissues of high-risk pregnant women. AB - AIM: This study was undertaken to investigate the existence of a periodontopathic bacterium, Fusobacterium nucleatum, in chorionic tissues of pregnant women, and the effects of F. nucleatum on human chorion-derived cells. MATERIALS AND METHODS: Oral and chorionic tissue samples were collected from 24 high-risk pregnant women and 15 normal pregnant women. The presence of F. nucleatum in the samples was detected using polymerase chain reaction. Chorion-derived cells and Toll-like receptor (TLR)-2 or TLR-4 gene-silenced chorion-derived cells were stimulated with F. nucleatum lipopolysaccharide (LPS). Interleukin (IL)-6 and corticotrophin-releasing hormone (CRH) levels in the culture supernatants were measured using ELISA. RESULTS: F. nucleatum was detected in all oral samples and seven chorionic tissues from the high-risk pregnant women, but was not detected in chorionic tissues from the normal pregnant women. F. nucleatum LPS significantly increased IL-6 and CRH secretion by chorion-derived cells. The F. nucleatum LPS-induced IL-6 and CRH levels were significantly reduced in TLR-2 or TLR-4 gene-silenced chorion-derived cells. CONCLUSIONS: We suggest that F. nucleatum is detected in chorionic tissues of high-risk pregnant women, but not in chorionic tissues of normal pregnant women, and that F. nucleatum induces IL-6 and CRH production via both TLR-2 and TLR-4 in chorion-derived cells. PMID- 22304675 TI - Mouse models for studying genetic influences on factors determining smoking cessation success in humans. AB - Humans differ in their ability to quit using addictive substances, including nicotine, the major psychoactive ingredient in tobacco. For tobacco smoking, a substantial body of evidence, largely derived from twin studies, indicates that approximately half of these individual differences in ability to quit are heritable genetic influences that likely overlap with those for other addictive substances. Both twin and molecular genetic studies support overlapping influences on nicotine addiction vulnerability and smoking cessation success, although there is little formal analysis of the twin data that support this important point. None of the current datasets provides clarity concerning which heritable factors might provide robust dimensions around which individuals differ in ability to quit smoking. One approach to this problem is to test mice with genetic variations in genes that contain human variants that alter quit success. This review considers which features of quit success should be included in a comprehensive approach to elucidate the genetics of quit success, and how those features may be modeled in mice. PMID- 22304678 TI - Use and costs of prescription medications and alternative treatments in patients with osteoarthritis and chronic low back pain in community-based settings. AB - OBJECTIVE: To evaluate the use and direct medical costs of pharmacologic and alternative treatments for patients with osteoarthritis (OA) and chronic low back pain (CLBP). METHODS: The LifeLinkTM Health Plan Claims Database was used to identify patients >=18 years old, diagnosed with OA (N = 112,951) or CLBP (N = 101,294). Of these patients, 64,085 with OA and 47,386 with CLBP received pain related treatments during CY2008 and were selected for inclusion. For patients in both cohorts, pharmacologic and alternative treatments, and direct medical costs were examined during CY2008. RESULTS: Opioids were the most frequently prescribed medication (>70%) in both groups, followed by nonselective nonsteroidal anti inflammatory drugs (>50%). Over 30% received antidepressants, >20% received benzodiazepines, and 15% in each group received sedative hypnotics. Use of alternative treatments was as follows: chiropractor, OA 11%, CLBP 34%; physical therapy, 20% in both groups; transcutaneous electrical nerve stimulations (TENS), OA 14%, CLBP 22%; acupuncture, hydrotherapy, massage therapy, and biofeedback, <3% in both groups. Mean (SD) total healthcare costs among these patients were, OA: $15,638 ($22,595); CLBP: $11,829 ($20,035). Pharmacologic therapies accounted for approximately 20% of these costs, whereas alternative treatments accounted for only 3% to 4% of the total costs. CONCLUSIONS: Patients with OA and CLBP used a variety of pain-related and adjunctive medications. Although, alternative treatments are widely recommended, we found limited use of several of these in clinical practice, potentially due to the source of our data (commercial claims). Further research is needed to ascertain the extent to which such therapies contribute to the total costs of OA and CLBP management. PMID- 22304679 TI - What limits [V(.)]O(2max)? A symposium held at the BASES Conference, 6 September 2010. AB - Three modern views about the factors limiting oxygen uptake in healthy humans are set against the original (early 1920s) concept of A. V. Hill and colleagues. The majority view for most of the intervening time has been that cardiac output is the essential limiting function. Among recent research in support of this contention is that, in quadrupeds, pericardiectomy, which allows greater diastolic filling, elevates maximum oxygen uptake; however, the relevance to bipedal exercise can be questioned. In any case, algebraic analyses of model systems indicate that all identifiable stages on the oxygen transport pathway, from pulmonary diffusion to oxidative phosphorylation in skeletal muscle mitochondria, materially influence maximum uptake. Thus, if a high cardiac output is to be of benefit, all the other steps must function better too. Nevertheless, these two viewpoints concur that the limit to maximum oxygen uptake is somatic. In contrast, there are strong indications that at altitudes where oxygen availability is about half that at sea level, cerebral oxygenation is a limiting factor, and some recent experiments raise the possibility that it might be a substantial influence at sea level also. Clearly, consensus cannot yet be reached on the question posed in the title. PMID- 22304680 TI - Improving access to palliative care through an innovative quality improvement initiative: an opportunity for pay-for-performance. AB - BACKGROUND: Improving access to palliative care is an important priority for hospitals as they strive to provide the best care and quality of life for their patients. Even in hospitals with longstanding palliative care programs, only a small proportion of patients with life-threatening illnesses receive palliative care services. Our two well-established palliative care programs in large academic hospitals used an innovative quality improvement initiative to broaden access to palliative care services, particularly to noncancer patients. METHODS: The initiative utilized a combination of electronic and manual screening of medical records as well as intensive outreach efforts to identify two cohorts of patients with life-threatening illnesses who, according to University HealthSystems Consortium (UHC) benchmarking criteria, would likely benefit from palliative care consultation. Given the differing cultures and structure of the two institutions, each service developed a unique protocol for identifying and consulting on suitable patients. RESULTS: Consultation rates in the target populations tripled following the initiative: from 16% to 46% at one hospital and from 15% to 48% at the other. Although two different screening and identification processes were developed, both successfully increased palliative care consultations in the target cohorts. CONCLUSION: Quality improvement strategies that incorporate pay-for-performance incentives can be used effectively to expand palliative care services to underserved populations. PMID- 22304681 TI - Efficacy and safety of testosterone in the management of hypoactive sexual desire disorder in postmenopausal women. AB - INTRODUCTION: Hypoactive sexual desire disorder (HSDD) is a common problem in postmenopausal women, but in the absence of an approved medical treatment in the United States, off-label testosterone use is widespread. Large, randomized controlled studies have demonstrated that transdermal testosterone improves sexual function and activity in postmenopausal women and has favorable short-term safety. However, a longer-term safety profile of testosterone must be established before a testosterone product for women is approved. AIM: To review current knowledge of the efficacy and safety of transdermal testosterone based on presentations at a satellite symposium during the 2011 annual meeting of the International Society for the Study of Women's Sexual Health. METHODS: Pertinent information included in the presentations was augmented with relevant articles from the peer-reviewed literature. MAIN OUTCOME MEASURES: The rationale for testosterone therapy and results from phase III and other clinical studies with the testosterone patch in postmenopausal women with HSDD and findings from studies investigating the cardiovascular, breast, and endometrial effects of testosterone therapy. RESULTS: Randomized, double-blind, placebo-controlled studies have established the efficacy of the transdermal testosterone patch for relieving symptoms of HSDD in surgically and naturally menopausal women with and without concomitant estrogen or estrogen/progestin therapy. The main side effects reported in clinical trials were increased hair growth and acne. Available safety data for testosterone, although not conclusive, were reassuring with respect to cardiovascular, breast, and endometrial outcomes. Interim data from a long-term phase III safety trial of a testosterone gel demonstrate a continued low rate of cardiovascular events and breast cancer in postmenopausal women at increased cardiovascular risk. CONCLUSION: Transdermal testosterone appears to be an effective and safe therapy for postmenopausal women with HSDD. PMID- 22304682 TI - Structural basis for differential insertion kinetics of dNMPs opposite a difluorotoluene nucleotide residue. AB - We have recently challenged the widely held view that 2,4-difluorotoluene (dF) is a nonpolar isosteric analogue of the nucleotide dT, incapable of forming hydrogen bonds (HBs). To gain a further understanding for the kinetic preference that favors dAMP insertion opposite a templating dF, a result that mirrors the base selectivity that favors dAMP insertion opposite dT by RB69 DNA polymerase (RB69pol), we determined presteady-state kinetic parameters for incorporation of four dNMPs opposite dF by RB69pol and solved the structures of corresponding ternary complexes. We observed that both the F2 and F4 substituent of dF in these structures serve as HB acceptors forming HBs either directly with dTTP and dGTP or indirectly with dATP and dCTP via ordered water molecules. We have defined the shape and chemical features of each dF/dNTP pair in the RB69pol active site without the corresponding phosphodiester-linkage constraints of dF/dNs when they are embedded in isolated DNA duplexes. These features can explain the kinetic preferences exhibited by the templating dF when the nucleotide incorporation is catalyzed by wild type RB69pol or its mutants. We further show that the shapes of the dNTP/dF nascent base pair differ markedly from the corresponding dNTP/dT in the pol active site and that these differences have a profound effect on their incorporation efficiencies. PMID- 22304683 TI - The influence of the degree of esterification on the release characteristics of in situ gelling pectin formulations for oral sustained delivery of paracetamol. AB - The aim of this study was to examine the effect of a change of the degree of esterification of pectin on the in situ gelation and release characteristics of 1.5% (w/v) pectin solutions over a wide pH range. Formulations of pectin with degrees of esterification of 9% (DE9) and 31% (DE31) containing complexed calcium ions formed gels in vitro at pH 1.2 as a consequence of cross-linking of the pectin chains by free calcium ions released from the complex. In vitro release of paracetamol from these gels was diffusion controlled. A sustained release of paracetamol was observed following oral administration of pectin DE9 and DE31 formulations to gastric acidity-controlled rats at pH 2.5 but only with DE9 formulations at pH 5.5. Examination of the stomach contents confirmed effective in situ gelation of pectin DE9 formulations at a gastric pH of 6 but there was no evidence of the gelation of pectin DE31 formulations at this pH. PMID- 22304685 TI - Structural properties of colloidal complexes between condensed tannins and polysaccharide hyaluronan. AB - Interactions of plant tannins with polysaccharide hyaluronan are studied by means of light scattering and small-angle X-ray scattering (SAXS). In this paper, we show that (1) the tannin-polysaccharide complexes remain stable in colloidal suspension; (2) the masses and structures of colloidal tannin-polysaccharide objects depend on the tannin degree of polymerization; and (3) the densities of tannin-polysaccharide aggregates are about 7 times lower than the density of a single solvated polysaccharide molecule. Short tannins and polysaccharides are aggregated in loose oligomeric structures whose sizes are comparable to a single polysaccharide molecule. Tannins longer than 10 nm and polysaccharides are aggregated in larger microgel-like particles whose sizes exceed 200 nm. PMID- 22304686 TI - New insights on the pathogenesis of ovarian carcinoma: molecular basis and clinical implications. AB - Ovarian carcinoma can be subdivided into two categories termed type I and type II. Type I tumours, usually having an indolent clinical behaviour, are often detected in early stage, and rarely harbour p53 gene mutations. Each histological type has a distinct molecular profile with mutations of genes involved in different signalling transduction pathways, such as KRAS, BRAF, CTNNB1, PTEN, PIK3CA and ARID1A. Type II tumours, accounting for 75% of the cases, have a very aggressive biological behaviour, are usually in advanced stage at presentation, harbour p53 gene mutations in 80% of the cases, and sometimes have alterations of homologous recombination (HR). Both type I and type II tumours arise from extra ovarian precursors. Serous carcinomas derive from tubal epithelium, endometrioid and clear cell carcinomas from endometrial tissue, and mucinous and Brenner tumours from transitional epithelial cells located near the tubo-peritoneal junction. These new concepts on the pathogenesis of ovarian carcinoma could deeply modify both the preventive approach in women with germ-line BRCA1 or BRCA2 mutations and the treatment of patients with advanced or recurrent disease. For instance, BRAF inhibitors could be used in low-grade serous carcinomas, PIK3CA inhibitors could be employed in clear cell carcinoma, and poly (ADP-ribose) polymerase inhibitors could be used not only in hereditary ovarian carcinoma but also in non-hereditary, high-grade serous ovarian carcinoma which sometimes shows defective HR. PMID- 22304687 TI - Adaptation as a mechanism for gain control in cockroach ON and OFF olfactory receptor neurons. AB - In many sensory systems adaptation acts as a gain control mechanism that optimizes sensory performance by trading increased sensitivity to low stimulus intensity for decreased sensitivity to high stimulus intensity. Adaptation of insect antennal olfactory receptor neurons (ORNs) has been studied for strong odour concentrations, either pulsed or constant. Here, we report that during slowly oscillating changes in the concentration of the odour of lemon oil, the ON and OFF ORNs on the antenna of the cockroach Periplaneta americana adapt to the actual odour concentration and the rate at which concentration changes. When odour concentration oscillates rapidly with brief periods, adaptation improves gain for instantaneous odour concentration and reduces gain for the rate of concentration change. Conversely, when odour concentration oscillates slowly with long periods, adaptation increases gain for the rate of change at the expense of instantaneous concentration. Without this gain control the ON and OFF ORNs would, at brief oscillation periods, soon reach their saturation level and become insensitive to further concentration increments and decrements. At long oscillation periods, on the other hand, the cue would simply be that the discharge begins to change. Because of the high gain for the rate of change, the cockroach will receive creeping changes in odour concentration, even if they persist in one direction. Gain control permits a high degree of precision at small rates when it counts most, without sacrificing the range of detection and without extending the measuring scale. PMID- 22304688 TI - Is S-nitrosocysteine a true surrogate for nitric oxide? AB - S-Nitrosothiol (RSNO) formation is one manner by which nitric oxide (*NO) exerts its biological effects. There are several proposed mechanisms of formation of RSNO in vivo: auto-oxidation of *NO, transnitrosation, oxidative nitrosylation, and from dinitrosyliron complexes (DNIC). Both free *NO, generated by *NO donors, and S-nitrosocysteine (CysNO) are widely used to study *NO biology and signaling, including protein S-nitrosation. It is assumed that the cellular effects of both compounds are analogous and indicative of in vivo *NO biology. A quantitative comparison was made of formation of DNIC and RSNO, the major *NO-derived cellular products. In RAW 264.7 cells, both *NO and CysNO were metabolized, leading to rapid intracellular RSNO and DNIC formation. DNIC were the dominant products formed from physiologic *NO concentrations, however, and RSNO were the major product from CysNO treatment. Chelatable iron was necessary for DNIC assembly from either *NO or CysNO, but not for RSNO formation. These profound differences in RSNO and DNIC formation from *NO and CysNO question the use of CysNO as a surrogate for physiologic *NO. Researchers designing experiments intended to elucidate the biological signaling mechanisms of *NO should be aware of these differences and should consider the biological relevance of the use of exogenous CysNO. PMID- 22304689 TI - Histamine reduces susceptibility to natural killer cells via down-regulation of NKG2D ligands on human monocytic leukaemia THP-1 cells. AB - Natural killer (NK) group 2D (NKG2D) is a key activating receptor expressed on NK cells, whose interaction with ligands on target cells plays an important role in tumorigenesis. However, the effect of histamine on NKG2D ligands on tumour cells is unclear. Here we showed that human monocytic leukaemia THP-1 cells constitutively express MHC class I-related chain A (MICA) and UL16-binding protein 1 on their surface, and incubation with histamine reduced the expression in a dose-dependent and time-dependent manner as assessed by flow cytometry. Interferon-gamma augmented the surface expression of the NKG2D ligands, and this augmentation was significantly attenuated by histamine. The histamine H1 receptor (H1R) agonist 2-pyridylethylamine and H2R agonist dimaprit down-regulated the expression of NKG2D ligands, and activation of H1R and H2R signalling by A23187 and forskolin, respectively, had the same effect, indicating that the histamine induced down-regulation of NKG2D ligands is mediated by H1R and H2R. Quantitative reverse transcription-PCR showed that mRNA levels of the NKG2D ligands and relevant microRNAs were not significantly changed by histamine. Histamine down regulated the surface expression of endoplasmic reticulum protein 5, and inhibition of matrix metalloproteinases did not impair this down-regulation, indicating that proteolytic shedding was not involved. Instead, pharmacological inhibition of protein transport and proteasome abrogated it, and histamine enhanced ubiquitination of MICA. Furthermore, histamine treatment significantly reduced susceptibility to NK cell-mediated cytotoxicity. These results suggest that histamine down-regulates NKG2D ligands through the activation of an H1R- and H2R-mediated ubiquitin-proteasome pathway and consequently reduces susceptibility to NK cells. PMID- 22304690 TI - The long-term outcome of transcutaneous electrical nerve stimulation in the treatment for patients with chronic pain: a randomized, placebo-controlled trial. AB - BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is an easy to use analgesic intervention. However, long-term randomized placebo-controlled studies with treatment periods of more than 3 months have not been executed to date. The aim of our study is to explore the long-term (1 year) time course of the treatment effects of TENS compared to placebo (sham TENS). METHOD: We performed a randomized placebo-controlled trial in patients with chronic pain (165), referred to a multidisciplinary pain center of a university hospital. Main outcome measures are the proportion of patients satisfied with treatment result and willing to continue treatment, pain intensity, pain disability, and perceived health status. RESULTS: Survival analysis of time courses of proportions of satisfied patients revealed no significant differences (P = 0.79; log-rank test) for TENS treatment compared to sham TENS. After 1 year, 30% (24/81) of the patients of the TENS group and 23% (19/82) of the sham TENS group were satisfied with treatment result. These patients experienced a mean overall improvement of 62.7% (n = 43). This effect was not significantly different between both groups. For satisfied patients, there were no differences in pain intensity or disability and perceived health status between the TENS and sham TENS group. CONCLUSIONS: Transcutaneous electrical nerve stimulation and sham TENS show similar effects in patients with chronic pain over a period of 1 year. We found support for a long sustained placebo effect. PMID- 22304691 TI - Coping strategies used by Pakistani parents living in the United Kingdom and caring for a severely disabled child. AB - PURPOSE: This study explores the coping strategies of Pakistani parents living in the UK and caring for children with severe learning disabilities. It examines factors that influenced participants' choice or ability to use the different strategies identified. METHOD: Qualitative design using in-depth interviews. RESULTS: Coping strategies included sharing care with others, using external support and recognizing and enjoying the rewards of caregiving. Parents used different strategies according to their appraisal of resources available and the perceived consequences of their action within their social milieu. CONCLUSIONS: Findings relating to cultural difference fit with a universalist approach. Coping strategies are not specific to the Pakistani population but certain characteristics of the strategies may be distinct to those used by parents with a different heritage. Antonovsky's work suggests that maintaining a sense of coherence makes a key difference to staying psychologically healthy in an apparently disordered world. Findings from this study fit with this theory. Parents derived meaning and a sense of purpose from the idea that their child's disability was from God. The rewards of caregiving and the strong moral imperative to care for one's own child contributed to understandings of caregiving as an activity worthy of investment. PMID- 22304692 TI - In vitro measurement of volatile release in model lipid emulsions using proton transfer reaction mass spectrometry. AB - The presence of fat in food plays an important role in the way aroma is released during consumption and in the creation of the overall sensory impression. Fat acts as a reservoir for lipophilic volatile compounds and modulates the timing and delivery of aroma compounds in a unique manner. Despite considerable research, reproducible in vitro methods for measuring the effect of fat on volatile release are lacking. An open in vitro cell was used to simulate the open human naso-oropharygeal system and was interfaced with a proton transfer reaction mass spectrometer (PTR-MS) to examine some of the fundamental effects of fat on dynamic volatile release in liquid fat emulsions. Lipid emulsions with various fat contents (0-20%) and droplet sizes (0.25, 0.5, and 5.0 MUM) were spiked with flavor volatiles representing a range of lipophilicity (K(o/w) = 1-1380). Preloaded syringes of spiked emulsion were injected into the cell, and temporal changes in release were measured under dynamic conditions. Significant differences in release curves were measured according to the lipid content of emulsions, the vapor pressure, and K(o/w) values of the volatile compounds. With increasing addition of fat, the critical volatile release parameters, maximum concentration (I(max)), time to maximum concentration (T(max)), and the integrated area under the concentration curve (AUC), were affected. The in vitro curves were reproducible and in agreement with theory and correlated with the preswallow phase of in vivo release data. An exponential model was used to calculate changes in mass transfer rates with increased fat addition. PMID- 22304694 TI - The relationship between cognitive function and non-prescribed therapy use in older adults. AB - OBJECTIVES: To examine the association of cognitive function with use of non prescribed therapies for managing acute and chronic conditions, and to determine whether use of non-prescribed therapies changes over time in relation to baseline cognitive function. METHODS: 200 community-dwelling adults aged 65 and older were recruited from three counties in south central North Carolina. Repeated measures of daily symptoms and treatment were collected on three consecutive days at intervals of at least one month. The Mini-Mental State Examination, the primary cognitive measure, was collected as part of the baseline survey. Data were collected on the daily use of common non-prescribed therapies (use of prayer, ignore symptoms, over-the-counter remedies, food and beverage therapies, home remedies, and vitamin, herb, or supplements) on each of the three days of the follow-up interviews for up to six consecutive months. RESULTS: Older adults with poorer cognitive function were more likely to pray and ignore symptoms on days that they experienced acute symptoms. Poorer cognitive function was associated with increased use of home remedies for treating symptoms related to existing chronic conditions. CONCLUSIONS: Cognitive function may play a role in why older patients use some non-prescribed therapies in response to acute and chronic conditions. PMID- 22304695 TI - Extranodal diffuse large B cell lymphoma of cutaneous follicle centre lymphoma type: a study of 24 patients with non-cutaneous primary limited stage extranodal diffuse large B cell lymphoma in support of a new concept. AB - AIMS: Follicle centre cell lymphoma of small cell type showing either a follicular or diffuse growth pattern similar to cutaneous follicle centre lymphoma (cFCL) has been recognized in extranodal non-cutaneous sites. Our aim was (i) to investigate whether diffuse large B cell lymphoma (DLBCL) of cFCL type could be identified in extranodal non-cutaneous sites and (ii) whether clinical characteristics similar to primary cFCL could be recognized. METHODS AND RESULTS: Of 24 extranodal non-cutaneous DLBCLs, nine (38%) had large centrocytoid morphology and 15 (62%) were either 'centrocytoid and centroblastic' or 'centroblastic and immunoblastic'. Six centrocytoid cases were Irf-4 negative, Bcl-6 positive and at most weakly CD10- or Bcl-2-positive by immunohistochemistry, consistent with DLBCL of cFCL type. All patients with cFCL type were stage IE and were significantly younger than other patients. Recurrences occurred in two patients and were exclusively extranodal. CONCLUSION: Our results suggest that DLBCL of cFCL type can be identified in extranodal non cutaneous sites and shows clinical characteristics similar to genuine cFCL. We propose to expand the concept of cFCL to encompass large cell lymphomas in extranodal sites. PMID- 22304696 TI - Mixed-valence nickel-iron dithiolate models of the [NiFe]-hydrogenase active site. AB - A series of mixed-valence nickel-iron dithiolates is described. Oxidation of (diphosphine)Ni(dithiolate)Fe(CO)(3) complexes 1, 2, and 3 with ferrocenium salts affords the corresponding tricarbonyl cations [(dppe)Ni(pdt)Fe(CO)(3)](+) ([1](+)), [(dppe)Ni(edt)Fe(CO)(3)](+) ([2](+)) and [(dcpe)Ni(pdt)Fe(CO)(3)](+) ([3](+)), respectively, where dppe = Ph(2)PCH(2)CH(2)PPh(2), dcpe = Cy(2)PCH(2)CH(2)PCy(2), (Cy = cyclohexyl), pdtH(2) = HSCH(2)CH(2)CH(2)SH, and edtH(2) = HSCH(2)CH(2)SH. The cation [2](+) proved unstable, but the propanedithiolates are robust. IR and EPR spectroscopic measurements indicate that these species exist as C(s)-symmetric species. Crystallographic characterization of [3]BF(4) shows that Ni is square planar. Interaction of [1]BF(4) with P-donor ligands (L) afforded a series of substituted derivatives of type [(dppe)Ni(pdt)Fe(CO)(2)L]BF(4) for L = P(OPh)(3) ([4a]BF(4)), P(p C(6)H(4)Cl)(3) ([4b]BF(4)), PPh(2)(2-py) ([4c]BF(4)), PPh(2)(OEt) ([4d]BF(4)), PPh(3) ([4e]BF(4)), PPh(2)(o-C(6)H(4)OMe) ([4f]BF(4)), PPh(2)(o C(6)H(4)OCH(2)OMe) ([4g]BF(4)), P(p-tol)(3) ([4h]BF(4)), P(p-C(6)H(4)OMe)(3) ([4i]BF(4)), and PMePh(2) ([4j]BF(4)). EPR analysis indicates that ethanedithiolate [2](+) exists as a single species at 110 K, whereas the propanedithiolate cations exist as a mixture of two conformers, which are proposed to be related through a flip of the chelate ring. Mossbauer spectra of 1 and oxidized S = 1/2 [4e]BF(4) are both consistent with a low-spin Fe(I) state. The hyperfine coupling tensor of [4e]BF(4) has a small isotropic component and significant anisotropy. DFT calculations using the BP86, B3LYP, and PBE0 exchange correlation functionals agree with the structural and spectroscopic data, suggesting that the SOMOs in complexes of the present type are localized in an Fe(I)-centered d(z(2)) orbital. The DFT calculations allow an assignment of oxidation states of the metals and rationalization of the conformers detected by EPR spectroscopy. Treatment of [1](+) with CN(-) and compact basic phosphines results in complex reactions. With dppe, [1](+) undergoes quasi disproportionation to give 1 and the diamagnetic complex [(dppe)Ni(pdt)Fe(CO)(2)(dppe)](2+) ([5](2+)), which features square-planar Ni linked to an octahedral Fe center. PMID- 22304697 TI - Cruciforms' polarized emission confirms disjoint molecular orbitals and excited states. AB - Steady-state and time-resolved polarized spectroscopy studies reveal that electronic excitation to the third excited state of 1,4-distyryl-2,5 bis(arylethynyl)benzene cruciforms results in fluorescence emission that is shifted an angle of ca. 60 degrees . This result is consistent with quantum chemical calculations of the lowest electronic excited states and their transition dipole moments. The shift originates from the disjointed nature of the occupied molecular orbitals being localized on the different branches of the cruciforms. PMID- 22304698 TI - Mastering improvement science skills in the new era of quality and safety: the Veterans Affairs National Quality Scholars Program. AB - RATIONALE, AIMS AND OBJECTIVES: Healthcare professionals need a new skill set to ensure the success of quality improvement in healthcare. The Department of Veterans Affairs (VA) initiated the VA National Quality Scholars fellowship in 1998; its mission is to improve the quality of care, ensure safety, accelerate healthcare re-design, and advance the improvement science by educating the next generation of leaders in quality and safety. We describe the critical need for leadership in quality and safety and interprofessional education, illustrate the curriculum, provide lessons learned by fellows, summarize key lessons learned from the implementation of an interprofessional education approach, and present most recent accomplishments. METHODS: Narrative review. RESULTS: As of 2011, 106 program alumni are embedded in the health care delivery system across the United States. Since 2009, when nurse fellows joined the program, of the first nine graduating interdisciplinary fellows, the tailored curriculum has resulted in five advanced academic degrees, 42 projects, 29 teaching activities, 44 presentations, 36 publications, six grants funded or submitted, and two awards. CONCLUSIONS: The VA National Quality Scholars program continues to nurture and develop leaders for the new millennium focusing on interprofessional education. The nations' health care systems need strong interdisciplinary leaders in advanced quality improvement science who are dedicated to improving the overall quality of health and health care. PMID- 22304699 TI - Fine structure in isotopic peak distributions measured using a dynamically harmonized Fourier transform ion cyclotron resonance cell at 7 T. AB - The fine structure of isotopic peak clusters in mass spectra of reserpine and substance P are measured using Fourier transform ion cyclotron resonance mass spectrometry at a 7 T magnetic field. The resolved peaks in the fine structure consist of (13)C, (15)N, (17)O, (18)O, (2)H, (33)S, (34)S, and combinations of them. A recently introduced high-resolution ion cyclotron resonance cell (Nikolaev, E. N.; Boldin, I. A.; Jertz, R.; Baykut, G. J. Am. Soc. Mass Spectrom. 2011, 22, 1125-1133) is used in these experiments. The positions of the experimentally obtained fine structure peaks on the mass scale agree with the isotopic distribution simulations with <=200 ppb error. Some deviation from the theoretical isotopic distribution is observed, less abundant peaks in the fine structure patterns are a little suppressed compared to the larger ones. We present a method for atomic composition determination using accurate mass data and fine isotopic structure of the mass spectrum. Our method combines the traditional atomic composition determination from accurate mass data by enumeration of all possible formulas within constraints defined a priori with the estimation of element coefficients from resolved isotopic structures. These estimated values allow one to narrow the search space for the composition and therefore to reduce the number of candidate formulas. PMID- 22304700 TI - Pitfalls in using the female sexual function index. PMID- 22304701 TI - From "sex toy" to intrusive imposition: a qualitative examination of women's experiences with vaginal dilator use following treatment for gynecological cancer. AB - INTRODUCTION: Regular use of vaginal dilators has been recommended as a prophylactic measure following radiation treatment for gynecological cancers in order to minimize vaginal stenosis and promote optimal healing of the vagina. Despite the well-established reluctance of women to adopt this practice, little is known about the difficulties and concerns associated with vaginal dilator use. AIM: To investigate women's experiences with the vaginal dilator and to understand the psychosocial factors that influence women's adoption of rehabilitative dilator use. METHODS: This is an exploratory qualitative study using semi-structured interviews with a sample of 10 women with a history of gynecological cancer and who were prescribed a vaginal dilator. Interviews were analyzed using the grounded theory method and examined for recurrent themes. MAIN OUTCOME MEASURE: The main outcome measure was a semi-structured interview comprised of open-ended questions designed to elicit information concerning topic areas relevant to gynecological cancer, vaginal dilator use, and sexuality. RESULTS: The analysis resulted in five main categories underlying the core category of "From 'sex toy' to intrusive imposition." These were: (i) embarrassing sex toy; (ii) reliving the invasion of treatment; (iii) aversive "hands-on" experience; (iv) not at the forefront of my recovery; and (v) minimizing the resistance. CONCLUSIONS: Rehabilitative vaginal dilator use is a complex, multifaceted, and personal phenomenon that carries deep psychological and emotional implications that make it intrusive. These findings may enhance the way in which vaginal dilators are introduced and help healthcare providers address better women's difficulties and concerns with the dilators. Ultimately, it may also lead to improved health maintenance and quality of life for women recovering from gynecological cancer. PMID- 22304702 TI - Lipase-sensitive polymeric triple-layered nanogel for "on-demand" drug delivery. AB - We report a new strategy for differential delivery of antimicrobials to bacterial infection sites with a lipase-sensitive polymeric triple-layered nanogel (TLN) as the drug carrier. The TLN was synthesized by a convenient arm-first procedure using an amphiphilic diblock copolymer, namely, monomethoxy poly(ethylene glycol) b-poly(epsilon-caprolactone), to initiate the ring-opening polymerization of the difunctional monomer 3-oxapentane-1,5-diyl bis(ethylene phosphate). The hydrophobic poly(epsilon-caprolactone) (PCL) segments collapsed and surrounded the polyphosphoester core, forming a hydrophobic and compact molecular fence in aqueous solution which prevented antibiotic release from the polyphosphoester core prior to reaching bacterial infection sites. However, once the TLN sensed the lipase-secreting bacteria, the PCL fence of the TLN degraded to release the antibiotic. Using Staphylococcus aureus (S. aureus) as the model bacterium and vancomycin as the model antimicrobial, we demonstrated that the TLN released almost all the encapsulated vancomycin within 24 h only in the presence of S. aureus, significantly inhibiting S. aureus growth. The TLN further delivered the drug into bacteria-infected cells and efficiently released the drug to kill intracellular bacteria. This technique can be generalized to selectively deliver a variety of antibiotics for the treatment of various infections caused by lipase secreting bacteria and thus provides a new, safe, effective, and universal approach for the treatment of extracellular and intracellular bacterial infections. PMID- 22304703 TI - Enhanced dissolution, stability and physicochemical characterization of ATRA/2 hydroxypropyl-beta-cyclodextrin inclusion complex pellets prepared by fluid-bed coating technique. AB - The aim of this work was to prepare stable all-trans-retinoic acid (ATRA)/2 hydroxypropyl-beta-cyclodextrin (HPCD) inclusion complex pellets with industrial feasible technology, the fluid-bed coating technique, using PVP K30 simultaneously as binder and reprecipitation retarder. The coating process was fluent with high coating efficiency. In vitro dissolution of the inclusion complex pellets in 5% w/v Cremopher EL solution was dramatically enhanced with no reprecipitation observed, and significantly improved stability against humidity (92.5% and 75% RH) and illumination (4500 lx +/- 500 lx) was achieved by HPCD inclusion. Differential scanning calorimetry and powder X-ray diffractometry confirmed the absence of crystallinity of ATRA. Fourier transform-infrared spectrometry revealed interaction between ATRA and HPCD adding evidence on inclusion of ATRA moieties into HPCD cavities. Solid-state (13)C NMR spectrometry indicated possible inclusion of ATRA through the polyene chain, which was the main reason for the enhanced photostability. It is concluded that the fluid-bed coating technique has the potential use in the industrial preparation of ATRA/HPCD inclusion complex pellets. PMID- 22304705 TI - Regulation of glutamate synthesis via inhibition of glutamate carboxypeptidase II (GCPII): an effective method to treat central and peripheral nervous system disorders. PMID- 22304704 TI - Predictors of warfarin use in atrial fibrillation in the United States: a systematic review and meta-analysis. AB - BACKGROUND: Despite warfarin's marked efficacy, not all eligible patients receive it for stroke prevention in AF. The aim of this meta-analysis was to evaluate the association between prescriber and/or patient characteristics and subsequent prescription of warfarin for stroke prevention in patients with atrial fibrillation (AF). METHODS: Observational studies conducted in the US using multivariate analysis to determine the relationship between characteristics and the odds of receiving warfarin for stroke prevention were identified in MEDLINE, EMBASE and a manual review of references. Effect estimates of prescriber and/or patient characteristics from individual studies were pooled to calculate odds ratios (ORs) with 95% confidence intervals. RESULTS: Twenty-eight studies reporting results of 33 unique multivariate analyses were identified. Warfarin use across studies ranged from 9.1%-79.8% (median=49.1%). There was a moderately strong correlation between warfarin use and year of study (r=0.60, p=0.002). Upon meta-analysis, characteristics associated with a statistically significant increase in the odds of warfarin use included history of cerebrovascular accident (OR=1.59), heart failure (OR=1.36), and male gender (OR=1.12). Those associated with a significant reduction in the odds of warfarin use included alcohol/drug abuse (OR=0.62), perceived barriers to compliance (OR=0.87), contraindication(s) to warfarin (OR=0.81), dementia (OR=0.32), falls (OR=0.60), gastrointestinal hemorrhage (OR=0.47), intracranial hemorrhage (OR=0.39), hepatic (OR=0.59), and renal impairment (OR=0.69). While age per 10-year increase (OR=0.78) and advancing age as a dichotomized variable (cut-off varied by study) (OR=0.57) were associated with significant reductions in warfarin use; qualitative review of results of studies evaluating age as a categorical variable did not confirm this relationship. CONCLUSIONS: Warfarin use has increased somewhat over time. The decision to prescribe warfarin for stroke prevention in atrial fibrillation is based upon multiple prescriber and patient characteristics. These findings can be used by family practice prescribers and other healthcare decision-makers to target interventions or methods to improve utilization of warfarin when it is indicated for stroke prevention. PMID- 22304706 TI - Tissue distribution of glutamate carboxypeptidase II (GCPII) with a focus on the central and peripheral nervous system. AB - Glutamate carboxypeptidase II, also known as prostate specific membrane antigen or folate hydrolase I, is a type II transmembrane 750 amino acid membrane-bound glycoprotein, with a molecular weight in the human form of approximately 100 kDa and a demonstrated metallopeptidase activity. At the synaptic level it hydrolyzes N-acetylaspartylglutamate to N-acetyl-aspartate and glutamate. Its localization in the animal and human nervous system has only recently been clearly established, since many of the older studies gave conflicting results, likely due to the use of poorly characterized antibodies lacking epitope mapping and proper controls (i.e. immunohistochemistry complemented by western blot analysis and enzyme activity determination). In this chapter, we will review the available literature describing the animal and human distribution of glutamate carboxypeptidase in the central and peripheral nervous system. PMID- 22304707 TI - Glutamate and multiple sclerosis. AB - Multiple sclerosis (MS) has been considered for a long time a typical inflammatory demyelinating disease of the central nervous system due to autoimmunity targeting oligodendrocytes with sparing of axons until advanced stages of the disease. For this reason, most of the earliest experimental studies focused on the role of cytokines and chemokines at the site of oligodendrocytes loss and on the importance in MS pathogenesis of classical inflammatory mechanisms. As a result, several attempts to treat MS through reduction of the local inflammatory milieau have been performed, leading to the current "immunomodulatory" treatment of the disease. However, more recently the importance of axonal loss and neurodegeneration even in the earliest stages of MS has been also recognized, and additional or concomitant players have been therefore searched. Evidence is now increasing that excessive glutamate is released at the site of demyelination and axonal degeneration in MS plaques, and the most probable candidates for this cellular release are infiltrating leukocytes and activated microglia. These observations are no longer simply preclinical results obtained in the MS animal model, i.e. experimental allergic encephalomyelitis, but have already been partially confirmed by post-mortem studies and in vivo analysis in MS patients, thus raising the possibility that modulation of glutamate release and transport as well as receptors blockade might be relevant targets for the development of future therapeutic interventions. PMID- 22304708 TI - Glutamate carboxypeptidase II: an overview of structural studies and their importance for structure-based drug design and deciphering the reaction mechanism of the enzyme. AB - Recent years witnessed rapid expansion of our knowledge about structural features of human glutamate carboxypeptidase II (GCPII). There are over thirty X-ray structures of human GCPII (and of its close ortholog GCPIII) publicly available at present. They include structures of ligand-free wild-type enzymes, complexes of wild-type GCPII/GCPIII with structurally diversified inhibitors as well as complexes of the GCPII(E424A) inactive mutant with several substrates. Combined structural data were instrumental for elucidating the catalytic mechanism of the enzyme. Furthermore the detailed knowledge of the GCPII architecture and protein inhibitor interactions offers mechanistic insight into structure-activity relationship studies and can be exploited for the rational design of novel GCPII specific compounds. This review presents a summary of structural information that has been gleaned since 2005, when the first GCPII structures were solved. PMID- 22304709 TI - Assessing glutamatergic function and dysfunction in peripheral tissues. AB - Glutamate is the major mediator of excitatory signaling in the mammalian central nervous system (CNS) and it has recently been described to have a central role in the transduction of sensory input in the peripheral nervous system (PNS), too. However, functional glutamatergic systems are expressed by peripheral non-neural tissues as well, such as heart, kidney, lungs, ovary, testis, blood and skin. Interestingly, glutamatergic alterations have been repeatedly described in these tissues in various neuropsychiatric diseases. Here we will review evidence suggesting that glutamate measurements obtained from sampling ex vivo peripheral cells can permit the assessment of the dynamics of glutamate release, uptake, receptor-mediated signaling, synthesis and degradation, and mirror homologous dysfunctions operative within the CNS in each single patient. Among all the available cell types we will focus on leukocytes, platelets and fibroblasts that can be easily obtained from patients multiple times without concerns related to post-mortem changes. Finally, we will briefly review another possibility, offered by testing plasma (and CSF) glutamate levels, allowing the indirect investigation of glutamate-mediated crosstalk between central and peripheral compartments. Technical pitfalls of these biomarkers will be contextually emphasized. PMID- 22304710 TI - GCPII variants, paralogs and orthologs. AB - Glutamate carboxypeptidase II (GCPII) and its splice variants, paralogs and human homologs represent a family of proteins with diverse tissue distribution, cellular localization and largely unknown function which have been explored only recently. While GCPII itself has been thoroughly studied from different perspectives, as clearly documented in this series of reviews, very little is known about other members of its family, even though they might be biologically relevant. Differential expression of individual GCPII splice variants is associated with tumor progression and prognosis of prostate cancer. The best studied GCPII homolog, GCPIII or NAALADase II, may be a valid pharmaceutical target for itself since it may compensate for a lack of normal GCPII enzymatic activity. Detailed molecular characterization of this family of proteins is thus very important not only with respect to the potential therapeutic use of GCPII inhibitors, but also for better understanding of the biological role of GCPII within as well as outside the nervous system. PMID- 22304711 TI - The role of glutamate signaling in pain processes and its regulation by GCP II inhibition. AB - Glutamate is the predominant excitatory neurotransmitter used by primary afferent synapses and neurons in the spinal cord dorsal horn. Glutamate and glutamate receptors are also located in areas of the brain, spinal cord and periphery that are involved in pain sensation and transmission. Not surprisingly, glutamate receptors have been an attractive target for new pain therapies. However, their widespread distribution and array of function has often resulted in drugs targeting these sites having undesirable side-effects. This chapter will review, in general terms, the current knowledge of glutamate and its effects at various glutamate receptors with regards to nociception. In addition, we will briefly review the glutamatergic drugs currently in use as treatments for pain, as well as known novel candidates in various stages of clinical trial. Lastly, we will summarize the data supporting a novel target for pain intervention by way of GCPII inhibition, which appears devoid of the side-effects associated with direct glutamate receptor antagonists and thus holds major promise for future therapy. GCPII (glutamate carboxypeptidase II) cleaves the prevalent neuropeptide NAAG into NAA and glutamate and there is widespread evidence and belief that targeting the glutamate derived from this enzymatic action may be a promising therapeutic route. PMID- 22304712 TI - Glutamate in CNS neurodegeneration and cognition and its regulation by GCPII inhibition. AB - Glutamate, first identified in 1866, is the primary excitatory neurotransmitter in the brain. While it is critically important in many highly regulated cortical functions such as learning and memory, glutamate can be much like the magic the Sorcerer's Apprentice used in Goethe's poem: when conjured under unregulated conditions glutamate can get quickly out of control and lead to deleterious consequences. Two broad types of glutamate receptors, the ionotropic and metabotropic, facilitate glutamatergic neurotransmission in the CNS and play key roles in regulating cognitive function. Excessive activation of these receptors leads to excitotoxicity, especially in brain regions that are developmentally and regionally vulnerable to this kind of injury. Dysregulation of glutamate signaling leads to neurodegeneration that plays a role in a number of neuropsychiatric diseases, prompting the development and utilization of novel strategies to balance the beneficial and deleterious potential of this important neurotransmitter. Inhibition of the enzyme glutamate carboxypeptidase II (GCPII) is one method of manipulating glutamate neurotransmission. Positive outcomes (decreased neuronal loss, improved cognition) have been demonstrated in preclinical models of ALS, stroke, and Multiple Sclerosis due to inhibition of GCPII, suggesting this method of glutamate regulation could serve as a therapeutic means for treating neurodegeneration and cognitive impairment. PMID- 22304714 TI - NAAG, NMDA receptor and psychosis. AB - At central synapses, glutamate is the main excitatory neurotransmitter. Once released from presynaptic terminals, glutamate activates a number of different glutamatergic receptors one of which is the ligand gated ionophore glutamatergic subtype N-methyl-D-aspartate receptors (NMDARs). NMDARs play a crucial role in controlling various determinants of synaptic function. N-acetylaspartylglutamate (NAAG) is the most prevalent peptide transmitter in the mammalian central nervous system. NAAG is released upon neuronal depolarization by a calcium-dependent process from glutamatergic and GABAergic neurons. It is cleaved by a specific peptidase located on astrocytes, glutamate carboxypeptidase type II (GCP-II), to N-acetylaspartate (NAA) and glutamate. Current evidence supports the hypothesis that NAAG is an endogenous agonist at G protein coupled mGluR3 receptors and an antagonist at NMDAR. In several disorders and animal models of human diseases, the levels of NAAG and the activity of GCP-II are altered in ways that are consistent with NAAG's role in regulation of glutamatergic neurotransmission. Several lines of evidence suggest that a dysfunction in glutamatergic via the NMDAR might be involved in schizophrenia. This hypothesis has evolved from findings that NMDAR antagonists such as phencyclidine (PCP or "angel dust"), produces a syndrome in normal individuals that closely resembles schizophrenia and exacerbates psychotic symptoms in patients with chronic schizophrenia. Recent postmortem, metabolic and genetic studies have provided evidence that hypofunction of discrete populations of NMDAR can contribute to the symptoms of schizophrenia, at least in some patients. The review outlines the role of endogenous NAAG at NMDAR neurotransmission and its putative role in the pathophysiology of schizophrenia. PMID- 22304715 TI - The role of glutamate in diabetic and in chemotherapy induced peripheral neuropathies and its regulation by glutamate carboxypeptidase II. AB - Glutamate has been implicated in the pathogenesis of several diseases on the central nervous system, but recent studies have also suggested that it can be involved also in the onset and course of peripheral neuropathies. Given the increasing evidence of this possibility, several attempts have been performed in order to modulate its activity. Among them, glutamate carboxypeptidase II (GCP II) inhibition demonstrated promising results in different models of peripheral nerve damage, including diabetic and toxic neuropathies. PMID- 22304713 TI - GCPII imaging and cancer. AB - Glutamate carboxypeptidase II (GCPII) in the central nervous system is referred to as the prostate-specific membrane antigen (PSMA) in the periphery. PSMA serves as a target for imaging and treatment of prostate cancer and because of its expression in solid tumor neovasculature has the potential to be used in this regard for other malignancies as well. An overview of GCPII/PSMA in cancer, as well as a discussion of imaging and therapy of prostate cancer using a wide variety of PSMA-targeting agents is provided. PMID- 22304717 TI - Structure-activity relationships of glutamate carboxypeptidase II (GCPII) inhibitors. AB - Glutamate carboxypeptidase II (GCPII, EC 3.4.17.21) is a zinc metallopeptidase that hydrolyzes N-acetylaspartylglutamate (NAAG) into N-acetylaspartate (NAA) and glutamate in the nervous system. Inhibition of GCPII has the potential to reduce extracellular glutamate and represents an opportune target for treating neurological disorders in which excess glutamate is considered pathogenic. Furthermore, GCPII was found to be identical to a tumor marker, prostate-specific membrane antigen (PSMA), and has drawn significant interest as a diagnostic and/or therapeutic target in oncology. Over the past 15 years, tremendous efforts have been made in the discovery of potent GCPII inhibitors, particularly those with phosphorus-, urea- and thiol-based zinc binding groups. In addition, significant progress has been made in understanding the three-dimensional structural characteristics of GCPII in complex with various ligands. The purpose of this review article is to analyze the structure-activity relationships (SAR) of GCPII inhibitors reported to date, which are classified on the basis of their zinc-binding group. SAR and crystallographic data are evaluated in detail for each of these series to highlight the future challenges and opportunities to identify clinically viable GCPII inhibitors. PMID- 22304718 TI - Hyperbranched polyglycerols as trimodal imaging agents: design, biocompatibility, and tumor uptake. AB - Combining various imaging modalities often leads to complementary information and synergistic advantages. A trimodal long-circulating imaging agent tagged with radioactive, magnetic resonance, and fluorescence markers is able to combine the high sensitivity of SPECT with the high resolution of MRI over hours and days. The fluorescence marker helps to confirm the in vivo imaging information at the microscopic level, in the context of the tumor microenvironment. To make a trimodal long-circulating probe, high-molecular-weight hyperbranched polyglycerols (HPG) were modified with a suitable ligand for (111)In radiolabeling and Gd coordination, and additionally tagged with a fluorescent dye. The resulting radiopharmaceutical and contrast agent was nontoxic and hemocompatible. Measured radioactively, its total tumor uptake increased from 2.6% at 24 h to 7.3% at 72 h, which is twice the increase expected due to tumor growth in this time period. Both in vivo MRI and subsequent histological analyses of the same tumors confirmed maximum HPG accumulation at 3 days post injection. Furthermore, Gd-derivatized HPG has an excellent contrast enhancement on T1 weighted MRI at 10* lower molar concentrations than commercially available Galbumin. HPG derivatized with gadolinium, radioactivity, and fluorescence are thus long-circulating macromolecules with great potential for imaging of healthy and leaky blood vessels using overlapping multimodal approaches and for the passive targeting of tumors. PMID- 22304719 TI - Adaptation of Salmonella enterica Hadar under static magnetic field: effects on outer membrane protein pattern. AB - BACKGROUND: Salmonella enterica serovar Hadar (S. Hadar) is a highly prevalent foodborne pathogen and therefore a major cause of human gastroenteritis worldwide. Outer membrane proteins whose production is often regulated by environmental conditions also play important roles in the adaptability of bacterial pathogens to various environments. RESULTS: The present study investigated the adaptation of S. Hadar under the effect of acute static magnetic field exposure (200 mT, 9 h) and the impact on the outer membrane protein pattern. Via two-dimensional electrophoresis (2-DE) and LC-MS/MS spectrometry, we compared the proteome of enriched-outer membrane fraction before and after exposure to a magnetic field. A total of 11 proteins, displaying more than a two fold change, were differentially expressed in exposed cells, among which 7 were up-regulated and 4 down-regulated. These proteins were involved in the integrity of cell envelope (TolB, Pal), in the response to oxidative stress (OmpW, dihydrolipoamide dehydrogenase, UspF), in the oxidative stress status (bacterioferritin), in virulence (OmpX, Yfgl) or in motility (FlgE and UspF). Complementary experiments associated the down-regulation of FlgE and UspF with an alteration of swarming, a flagella-driven motility, under SMF. Furthermore, the antibiotic disc diffusion method confirmed a decrease of gentamicin susceptibility in exposed cells. This decrease could be partly associated with the up-regulation of TolC, outer membrane component of an efflux pump. OmpA, a multifunctional protein, was up-regulated. CONCLUSIONS: SMF (200 mT) seems to maintain the cell envelope integrity and to submit the exposed cells to an oxidative stress. Some alterations suggest an increase of the ability of exposed cells to form biofilms. PMID- 22304720 TI - Hemopressin forms self-assembled fibrillar nanostructures under physiologically relevant conditions. AB - The nonapeptide hemopressin, which is derived from the alpha chain of hemoglobin, has been reported to exhibit inverse agonist activity against the CB1 receptor. Administration of this peptide in animal models led to decreased food intake and elicited hypotensive and antinociceptive effects. On the basis of hemopressin's potential in therapeutic applications and the lack of a structure-activity relationship study in literature, we aimed to determine the conformational features of hemopressin under physiological conditions. We conducted transmission electron microscopy experiments of hemopressin, revealing that it self-assembles into fibrils under aqueous conditions at pH 7.4. Circular dichroism and nuclear magnetic resonance experiments indicate that the peptide adopts a mostly extended beta-like structure, which may contribute to its self-assembly and fibril formation. PMID- 22304721 TI - Synergistic effect on the treatment of menorrhagia by endometrial biopsy followed by contemporaneous insertion of the levonorgestrel intrauterine system. AB - OBJECTIVE: To evaluate the efficacy of endometrial biopsy followed by intrauterine system-releasing levonorgestrel (LNG-IUS) insertion in the treatment of women with menorrhagia. METHOD: This was a retrospective, non-comparative study. Ninety-two patients who had menorrhagia due to non-malignant causes were sequentially recruited into the study over a 3-year period (age range 29-51 years). Patients with a uterine size more than 12 weeks were not included. A LNG releasing intrauterine system was inserted during the mid-cycle immediately after an endometrial biopsy was taken. One year after the closure of the study period, the women recruited were then contacted by telephone or by direct questioning at the outpatient clinic as to the outcome of the above treatment. RESULTS: The most common (15%) complaint regarding bleeding patterns at 3-6 months after insertion was spotting and intermenstrual bleeding. Following the introduction of the LNG IUS, six women required a hysterectomy for various reasons. The remaining 86 women (93.5%) continued the use of LNG-IUS. CONCLUSION: LNG-IUS following an endometrial biopsy is an effective treatment for menorrhagia due to benign causes and could be an alternative to other forms of medical and surgical treatments. PMID- 22304722 TI - Selenide ions as catalysts for homo- and crossed-Tishchenko reactions of expanded scope. AB - Selenide ions have been shown to catalyze the Tishchenko reaction for the first time. These catalysts are superior to previously reported thiolate analogues and promote the disproportionation of aldehydes with increased reaction rates and broader scope at lower catalyst loadings and temperatures. Significantly improved catalyst performance was also observed in the aryl selenide mediated crossed intermolecular Tishchenko reaction. PMID- 22304723 TI - [Hand washing: comparison between professionals and students behaviours in a large University hospital of Rome]. AB - The main objective of the study is assessing knowledge, opinions and compliance with the procedures of health professionals (physician, nurses, medical and nursing students) about Hand Hygiene (HH). There is a number of research which indicates that physicians respect less than nurses Hand Hygiene, there are a smaller number which investigates the differences in the attitude of the aforementioned subjects during their studies. A questionnaire was administered to a sample of 756 participants (252 doctors, 268 nurses, 117 nursing students and 119 students of medicine) at a large University Hospital in Rome, to determine their knowledge, compliance and procedures with Hand Hygiene. Knowledge of medical students is lower than that of nursing students, as well as they have lower values in adherence to practice. In both HH Beliefs Scale (HBS) and HH Practices Inventory (HHPI) questionnaires, nursing students have higher scores than nurses, doctors and medical students. The questions on the use of alcohol based cleaners have been those where there was the lowest number of correct responses, across all professions. Physicians compared to nurses have a lower adherence to Hand Hygiene. Future research should clarify what the differences are in the construction of the study on the practice of washing hands, what are the barriers to health professionals and best methods for teaching habits, namely the effectiveness of hand washing. Professionals should be more involved in the fight against Healthcare-associated infections. PMID- 22304724 TI - [Quality of life in people with heart failure: role of telenursing]. AB - The quality of life is a multi-dimensional phenomenon which can be analyzed in different terms such as the physical, social and psychological status of the individual. Assessment of quality of life is a priority aspect in patients with cardiac deficiency since it is a chronic, mainly unstable, pathology. The study described was aimed at evaluating the quality of life in such patients by means of a tele-nursing project. Fifty patients were contacted by phone and asked to fill in a Kansas City Cardiomyopathy Questionnaire (KCCQ) every 2 weeks for 3 times: they were given detailed information regarding pharmacological and other types of treatment, and how to behave in the event of complications. The 23 items of the questionnaire regarded physical limitations, evaluation of symptoms, self care and knowledge, perceived quality of life and social status. The results of the study showed an overall improvement in the quality of life of the patient sample , more noticeable in males with respect to females. PMID- 22304725 TI - [Risk analysis in the process of administering drugs in the emergency departments care: a multicenter observational study]. AB - Mistakes in providing medication are amongst main problems in National Health Service. The literature shows that drug's errors administration occur much more frequently in emergency departments than in other care settings. Main objective is to identify most commonly mistakes, recorded in nursing clinical practice, occurring during drugs administration. A secondary objective is to identify factors that may contribute to errors and possible preventive measures. A multicentre survey was conducted, administering an anonymous questionnaire to 206 nurses of 7 wards of 4 health services in Lombardia and Veneto region of Italy. The self-compiled questionnaire is composed by 15 questions. Informations were collected by a third-party nurse. Responders to test were 150 (72.8%). Main results show that 81 nurses (54%) administered a wrong drug dose, as well as 80 health care professional (53.3%) gave one or more drug at a different time from what was prescribed. It was also found a statistically significant association between improper performance of diagnostic tests and health care professionals age. Moreover, a strong linear association between medication error reporting and nurses was found. Educating nurses about accident reporting system to enhance patient safety culture is highly recommended. Our results could be used in programs aimed to promote medication error recognition and reduce or eliminate barriers to communication. PMID- 22304726 TI - [Planning and activation of a nursing consultancy service with formal recognition inside the San Giovanni Bosco Hospital of Turin]. AB - In some countries the figure of the Consultant Nurse already exists. The literature highlights the experience of the United Kingdom has formally defined the role and profile. In Italy there are few experiences in this area and all local initiative, although the Code of Ethics recognizes the nurse the opportunity to engage in counseling. In the Hospital San Giovanni Bosco di Torino as a result of increased complexity of patients to be treated has been developed at the informal advisory nursing. The aim of this paper is to describe the methodology used for the realization of plans to activate a service of advice nursing, recognized, in the Presidio and to present the results achieved from its application. It is a working group, reviewed the literature and shared the definition of "Nurse Consultant". This is done to administration of a validated questionnaire to map the types of assistance required and paid and payable, graduation of the types detected by means of a weighing system based on frequency, urgency and seriousness, elaboration of the structure of each profile with the declination of the requirements enabling focus groups with experienced professionals, develop a procedure for the activation of the advice and the schedule training. Results are identification of 5 types of advice and drafting of the profile priority, establishment of requirements for the suitability of staff to cover the position and drafting an operating procedure which governs the operation of the service within the Presidio. PMID- 22304727 TI - [Nursing managers: study to assess the expectations of nursing coordinators in a Northern Italian Hospital]. AB - In modern health-care , nursing managers play a strategic role in improving the quality of care and the skills of carers, since management and leadership strategies are known to be decisive in the deployment of resources and professional development. The aim of this study is to present the opinions and expectations of nursing coordinators regarding their managerial role. During the creation of a nursing service unifying the management of 3 local health authorities in Northern Italy, with different organizational and professional features, nursing coordinators were asked to fill in a questionnaire. Results showed that a priority aspect of the managerial role is to assess the appropriateness of care and the use of resources Their answers showed that they hoped for a style of management founded on aspects related to clinical government. For the style of leadership, they emphasized dedication to work, participation of staff in decision-making, group information and providing support in areas needing improvement. Although the study was territorial , it confirmed international guide-lines regarding the policies which give value to investments in the quality of organization and can be considered a point of reference for planning and creating future nursing services. PMID- 22304728 TI - Positive and negative impact of caregiving to older adults: a structural equation model. AB - Caregivers represent an important source of care for older adults. Many studies focused on the negative aspects of elder caregiving but few studies have analyzed also the positive effects. In addition, no studies have considered contemporarily the positive and the negative impact of caregiving to elderly people on the same people using a structural equation modeling. The purpose of this study was to examine the contribution of elder care recipient factors, caregiver factors and caregiving factors in determining the positive and negative impact of informal caregiving to older adults using a structural equation model. A cross-sectional design was used to study eighty caregivers of older people. Several instruments were used to measure elder care recipient factors (functionality, cognition, behavior); caregiver factors (socio-demographics, depression, stress, quality of life, and perceived health); caregiving factors (time from caregiving, time of care, social restriction, place of living, expenses, and living with the elder care recipient); and the positive and the negative impact of caregiving. Caregivers were 59.7 years old while elderly people were 84.0. Several factors were significantly correlated with the positive and negative impact of caregiving. However, when these factors were entered in a structural equation model, only female gender and social restriction predicted the negative impact, while caregiver's quality of life and caregiving expenses predicted both the positive and the negative impact. The results of this study suggest a new framework of caregiving to older adults where the outcomes depend more on caregiver and caregiving factors than on older person characteristics. More research is needed with a larger sample to test further the model outlined in this study. PMID- 22304729 TI - Rapid synaptic potentiation within the anterior cingulate cortex mediates trace fear learning. AB - Although the cortex has been extensively studied in long-term memory storage, less emphasis has been placed on immediate cortical contributions to fear memory formation. AMPA receptor plasticity is strongly implicated in learning and memory, and studies have identified calcium permeable AMPA receptors (CP-AMPARs) as mediators of synaptic strengthening. Trace fear learning engages the anterior cingulate cortex (ACC), but whether plastic events occur within the ACC in response to trace fear learning, and whether GluN2B subunits are required remains unknown. Here we show that the ACC is necessary for trace fear learning, and shows a rapid 20% upregulation of membrane AMPA receptor GluA1 subunits that is evident immediately after conditioning. Inhibition of NMDA receptor GluN2B subunits during training prevented the upregulation, and disrupted trace fear memory retrieval 48 h later. Furthermore, intra-ACC injections of the CP-AMPAR channel antagonist, 1-naphthylacetyl spermine (NASPM) immediately following trace fear conditioning blocked 24 h fear memory retrieval. Accordingly, whole cell patch clamp recordings from c-fos positive and c-fos negative neurons within the ACC in response to trace fear learning revealed an increased sensitivity to NASPM in recently activated neurons that was reversed by reconsolidation update extinction. Our results suggest that trace fear learning is mediated through rapid GluN2B dependent trafficking of CP-AMPARs, and present in vivo evidence that CP-AMPAR activity within the ACC immediately after conditioning is necessary for subsequent memory consolidation processes. PMID- 22304730 TI - Non-heme iron sensors of reactive oxygen and nitrogen species. AB - SIGNIFICANCE: In bacteria, transcriptional responses to reactive oxygen and nitrogen species (ROS and RNS, respectively) are typically coordinated by regulatory proteins that employ metal centers or reactive thiols to detect the presence of those species. This review is focused on the structure, function and mechanism of three regulatory proteins (Fur, PerR, and NorR) that contain non heme iron and regulate the transcription of target genes in response to ROS and/or RNS. The targets for regulation include genes encoding detoxification activities, and genes encoding proteins involved in the repair of the damage caused by ROS and RNS. RECENT ADVANCES: Three-dimensional structures of several Fur proteins and of PerR are revealing important details of the metal binding sites of these proteins, showing a surprising degree of structural diversity in the Fur family. CRITICAL ISSUES: Discussion of the interaction of Fur with ROS and RNS will illustrate the difficulty that sometimes exists in distinguishing between true physiological responses and adventitious reactions of a regulatory protein with a reactive ligand. FUTURE DIRECTIONS: Consideration of these three sensor proteins illuminates some of the key questions that remain unanswered, for example, the nature of the biochemical determinants that dictate the sensitivity and specificity of the interaction of the sensor proteins with their cognate signals. PMID- 22304731 TI - S100A9 a new marker for monocytic human myeloid-derived suppressor cells. AB - Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of cells that negatively regulate the immune response during tumour progression, inflammation and infection. Only limited data are available on human MDSC because of the lack of specific markers. We have identified members of the S100 protein family-S100A8, S100A9 and S100A12 - specifically expressed in CD14(+) HLA-DR( /low) MDSC. S100A9 staining in combination with anti-CD14 could be used to identify MDSC in whole blood from patients with colon cancer. An increase in the population of CD14(+) S100A9(high) MDSC was observed in the peripheral blood from colon cancer patients in comparison with healthy controls. Finally, nitric oxide synthase expression, a hallmark of MDSC, was induced in CD14(+) S100A9(high) upon lipopolysaccharide/interferon-gamma stimulation. We propose S100 proteins as useful markers for the analysis and further characterization of human MDSC. PMID- 22304732 TI - Diphtheria in the postepidemic period, Europe, 2000-2009. AB - Diphtheria incidence has decreased in Europe since its resurgence in the 1990s, but circulation continues in some countries in eastern Europe, and sporadic cases have been reported elsewhere. Surveillance data from Diphtheria Surveillance Network countries and the World Health Organization European Region for 2000-2009 were analyzed. Latvia reported the highest annual incidence in Europe each year, but the Russian Federation and Ukraine accounted for 83% of all cases. Over the past 10 years, diphtheria incidence has decreased by >95% across the region. Although most deaths occurred in disease-endemic countries, case-fatality rates were highest in countries to which diphtheria is not endemic, where unfamiliarity can lead to delays in diagnosis and treatment. In western Europe, toxigenic Corynebacterium ulcerans has increasingly been identified as the etiologic agent. Reduction in diphtheria incidence over the past 10 years is encouraging, but maintaining high vaccination coverage is essential to prevent indigenous C. ulcerans and reemergence of C. diphtheriae. PMID- 22304733 TI - Plesiomonas shigelloides infection, Ecuador, 2004-2008. AB - Diarrheal risk associated with Plesiomonas shigelloides infection was assessed in rural communities in northwestern Ecuador during 2004-2008. We found little evidence that single infection with P. shigelloides is associated with diarrhea but stronger evidence that co-infection with rotavirus causes diarrhea. PMID- 22304734 TI - Computational and biological evaluation of quinazolinone prodrug for targeting pancreatic cancer. AB - Our concept of enzyme-mediated cancer imaging and therapy aims to use radiolabeled compounds to target hydrolases over-expressed on the extracellular surface of solid tumors. A data mining approach identified extracellular sulfatase 1 (SULF1) as an enzyme expressed on the surface of pancreatic cancer cells. We designed, synthesized, and characterized 2-(2'-sulfooxyphenyl)-6-iodo-4 (3H)-quinazolinone (IQ(2-S)) as well as its radioiodinated form ((125) IQ(2-S)) as a prodrug with potential for hydrolysis by SULF1. IQ(2-S) was successfully docked in silico into three enzymes - homolog of SULF1, alkaline phosphatase, and prostatic acid phosphatase. The incubation of (125) IQ(2-S) and (125) IQ(2-P) with the three enzymes in solution confirms the docking results and enzyme selectivity for the analogs. The hydrolysis of both radioactive compounds produces the water-insoluble, fluorescent product 2-(2'-hydroxyphenyl)-6-[(125) I]iodo-4-(3H)-quinazolinone ((125) IQ(2-OH)). The in vitro incubation of (127) IQ(2-S) and (127) IQ(2-P) with pancreatic, ovarian, and prostate cancer cells expressing studied hydrolases also results in their hydrolysis and the precipitation of (127) IQ(2-OH) fluorescent crystals on the cell surface. To our knowledge, these findings are the first to report the targeting of a radioactive substrate to SULF1 and that this prodrug may be potentially useful in the imaging ((123) I/(124) I/(131) I) and radiotherapy ((131) I) of pancreatic cancer. PMID- 22304735 TI - Development of a novel tablet-in-capsule formulation of mesalamine for inflammatory bowel disease. AB - OBJECTIVE: The objective of the present work was to develop a tablet-in-capsule type of multiunit system, which releases the drug in a controlled manner at pre programmed time intervals. METHODS: The system consists of an enteric-coated hydroxypropyl methylcellulose capsule filled with four units of mesalamine minitablets, each of which was further coated with different ratios of Eudragit((r)) E100 and Eudragit((r)) RS100. RESULTS: In vitro evaluation of tablets coated with Eudragit((r)) E100 and Eudragit((r)) RS100 at different pH conditions revealed that at lower pH levels (2.0, 3.6 and 5.5 pH), the drug release is mainly governed by the dissolution of Eudragit((r)) E100 from the Eudragit((r)) E100 and Eudragit((r)) RS100 coat. In vitro evaluation of capsules enteric coated with Eudragit((r)) L100 and Eudragit((r)) S100 revealed that a maximum lag time of 3 h and 4 h was obtained, respectively. In vivo roentgenographic evaluation in rabbits revealed that the developed system remained intact until it reaches the targeted region of the gastrointestinal tract, i.e. ileum and colon, where the tablets were released after the dissolution of the enteric coat Eudragit((r)) L100 and Eudragit((r)) S100, respectively. CONCLUSION: The developed system exhibited a promising targeting behavior and hence may be used for the treatment of inflammatory bowel disease. PMID- 22304736 TI - Effects of reminiscence interventions on psychosocial outcomes: a meta-analysis. AB - OBJECTIVES: This study integrated results from controlled trials of reminiscence interventions. METHODS: Meta-analysis was used to aggregate results from 128 studies on 9 outcome VARIABLES. RESULTS: Compared to non-specific changes in control-group members, moderate improvements were observed at posttest with regard to ego-integrity (g=0.64) and depression (g=0.57 standard deviation units). Small effects were found on purpose in life (g=0.48), death preparation (g=0.40), mastery (g=0.40), mental health symptoms (g=0.33), positive well-being (g=0.33), social integration (g=0.31), and cognitive performance (g=0.24). Most effects were maintained at follow-up. We observed larger improvements of depressive symptoms in depressed individuals (g=1.09) and persons with chronic physical disease (g=0.94) than in other individuals, and in those receiving life review therapy (g=1.28) rather than life-review or simple reminiscence. Moderating effects of the control condition were also detected. CONCLUSIONS: Reminiscence interventions affect a broad range of outcomes, and therapeutic as well as preventive effects are similar to those observed in other frequently used interventions. PMID- 22304737 TI - Nurse preparedness for the non-communicable disease escalation in Thailand: a cross-sectional survey of nurses. AB - Chronic diseases are now the largest cause of mortality in Thailand, and form an increasingly large portion of the healthcare landscape. In the Thai health system, many patients with chronic conditions receive care and disease management services from nurses, yet specialized training in chronic diseases is not currently part of standard nursing degree programs. Given the evolving epidemiology of the Thailand population, we questioned whether practicing nurses remain confident in their knowledge and skills in chronic disease management. We conducted a cross-sectional, self-efficacy survey of nurses in eight randomly selected provinces in Thailand, receiving 468 responses. Nurse self-efficacy was analyzed in prominent chronic disease types, including cancer, hypertension, diabetes, heart disease, cerebrovascular diseases, and pulmonary diseases. Factors, such as geographic location, education level, continuing education experience, and hospital size, were found to significantly affect nurse self efficacy levels; nurses highly prioritized additional training in heart diseases and cerebrovascular diseases, followed by hypertension, cancer, and diabetes. PMID- 22304738 TI - Nursing contribution to the rehabilitation of older patients: patient and family perspectives. AB - AIMS: This article reports a study of the perspective of older patients and their family members on the role of nurses in inpatient rehabilitation. BACKGROUND: Rehabilitation services are used increasingly by older patients as life expectancy increases. The role of rehabilitation nurses in the multidisciplinary team has, however, yet to be clearly articulated. Previous research has focussed on the views of health professionals about nursing involvement in rehabilitation, but none has sought family members' perspectives. With the expectation of patient-centred care, it is important to consider what older patients and their families expect and require from nurses. DESIGN: Grounded theory was used to collect and analyse data from interviews in an inpatient rehabilitation unit in New Zealand with seven patients, aged 72-89 years, and six family members, during 2009-2010. FINDINGS: A substantive theory was developed which recognizes that the older patient values the relationship they build with nurses more than any specific role nurses perform. Participants acknowledged that rehabilitation nurses' roles included 'looking after', 'stepping in' and 'coaching independence' but 'best fit' nurses were identified by patients based on their 'nature', 'being available' and 'being attuned' to the patient's individual needs. If a 'connection' was formed, then this 'best fit relationship' maximized the older person's motivation to participate in his or her rehabilitation therapy. CONCLUSION: Patients and family members appreciate 'best fit relationships' where nurses seek to enter into the older person's world of disability to form a partnership which enhances their motivation to achieve independence. PMID- 22304739 TI - Minimally invasive lithium disilicate ceramic veneers fabricated using chairside CAD/CAM: a clinical report. AB - This clinical report describes the use of modern CAD/CAM technology combined with a conventional impression technique to treat a malformed tooth with ceramic veneer in a single appointment. A thin veneer (0.4 mm) made of lithium disilicate ceramic was used to correct the shape of the malformed tooth with a minimally invasive preparation using a chairside CAD/CAM system. Thus the treatment can be performed during one appointment. To facilitate the CAD/CAM process and fabrication of the veneer, a scanable model fabricated on a modified gypsum definitive cast was used. The malformed tooth was corrected on the cast by use of a composite resin and an impression was then made. This trimmed impression was used intraorally during the scanning process to facilitate fabrication of the veneer. PMID- 22304740 TI - A three-appointment alternative treatment protocol for fabricating an implant supported milled bar overdenture. AB - This article describes an alternative impression technique for the fabrication of an implant-supported bar overdenture using the duplicated satisfactory interim denture as a custom tray for the implant-level impression. The primary advantage of this technique is that all the information needed for the definitive prosthesis fabrication is obtained from the interim denture and then transferred to the laboratory in a single appointment. However, this technique may be contraindicated for severely misaligned implants that require extensive reduction of the duplicated denture. PMID- 22304741 TI - Effect of axial wall modification on the retention of cement-retained, implant supported crowns. AB - STATEMENT OF PROBLEM: Compromised angulation of implants may result in abutment preparation that is less than ideal. Compromised abutment preparation may affect the retention of implant-retained crowns. PURPOSE: The purpose of this study was to investigate the effect of 5 implant abutment designs on the retention of cement-retained crowns by varying the number and position of the axial walls. MATERIAL AND METHODS: Five prefabricated abutments were attached to an implant analog and embedded in an acrylic resin block. The first abutment was left intact without modification. Axial walls were partially removed from the remaining abutments to produce abutments with 3 walls, 2 adjacent walls, 2 opposing walls, and 1 wall. Five crowns were made for each group. The screw access channel for the first abutment was completely filled with composite resin and the rest were partially filled. The retentive surface area of each abutment was calculated. Crowns were cemented with zinc phosphate cement. Tensile force was applied to separate the castings from the abutments. Peak load to dislodgment was recorded. A 1-way ANOVA was used to test for a significant difference followed by the Tukey Honestly Significant Difference test (alpha=.05). RESULTS: The abutment with 2 opposing axial walls had significantly higher retention than that of all other groups (F=149.9, df =24, P<.001). The abutment with 3 walls exhibited the second highest retention and was significantly greater than abutments with 2 adjacent walls, 1, and 4 walls. Abutments with 2 adjacent walls and 1 wall were not significantly different from each other. The unmodified abutment with 4 walls exhibited the lowest retention despite having a large retentive surface area. CONCLUSIONS: The retention of cemented crowns on implant abutments is influenced by the number and position of axial walls. PMID- 22304742 TI - Effect of different grit sizes of diamond rotary instruments for tooth preparation on the retention and adaptation of complete coverage restorations. AB - STATEMENT OF PROBLEM: Internal adaptation and retention are important factors for the longevity of crown restorations. However, how tooth surface roughness associated with diamond rotary cutting instruments affects the retention and internal adaptation of complete coverage restorations remains unknown. PURPOSE: This study evaluated the relationship between the surface roughness of prepared teeth and the internal adaptation and retention of complete coverage restorations after preparation with diamond rotary cutting instruments of different grit sizes. MATERIAL AND METHODS: Ninety-two extracted human teeth were divided into 4 groups and assigned to different final grit sizes of the diamond rotary instruments used for preparation following a grit decreasing sequence from coarse (125 to 150 MUm), to medium (106 to 125 MUm), to fine (53 to 63 MUm), to extra fine (20 to 30 MUm). After preparation, the surface roughness of 32 teeth was measured with a profilometer. The other 60 teeth were prepared as abutments, with 28 of these teeth used to measure microleakage and cement thickness. The remaining 32 teeth were used to test the retention between teeth and nickel chromium alloy crowns with a universal testing machine. The data were analyzed with a 1-way ANOVA and Fisher's LSD post hoc multiple comparison tests to determine significant intergroup differences in surface roughness and retention force (alpha=.05). Microleakage scores and cement thickness were analyzed with the Kruskal-Wallis rank sum test; these were also conducted as multiple comparison tests (alpha=.05). RESULTS: The teeth prepared with the coarsest diamond rotary cutting instruments showed the highest mean surface roughness (SD) (4.8 (0.4) MUm), and those prepared with the finest diamond rotary instruments had the lowest mean cement thickness (0.5 (1.2) MUm; P<.001 when compared to teeth in the coarse group). The finer surfaces showed less microleakage (P =.03). However, no significant differences in retention were found (P=.19) across the groups. CONCLUSIONS: Teeth prepared with the finer grit rotary instruments have smoother tooth surfaces and crown restorations with better internal adaptation. The grit size of the diamond rotary cutting instruments does not affect the removal force between the complete coverage crown and the prepared tooth. PMID- 22304743 TI - Effect of surface conditioning with airborne-particle abrasion on the tensile strength of polymeric CAD/CAM crowns luted with self-adhesive and conventional resin cements. AB - STATEMENT OF PROBLEM: Adhesively bonded, industrially polymerized resins have been suggested as definitive restorative materials. It is claimed that such resins present similar mechanical properties to glass ceramic. PURPOSE: The purpose of this study was to assess the tensile strength of polymeric crowns after conditioning with 2 different protocols: luted with self-adhesive or with conventional resin cements to dental abutments. MATERIAL AND METHODS: Human teeth were prepared for crowns and divided into 13 groups (N=312, n=24 per group). Polymeric crowns were CAD/CAM fabricated and divided into 3 groups depending on different surface conditioning methods: A) No treatment, B) airborne-particle abrasion with 50 MUm alumina, and C) airborne-particle abrasion with 110 MUm alumina. Thereafter, the crowns were luted on dentin abutments with the following cements: 1) RXU (RelyX Unicem, self-adhesive), 2) GCM (G-Cem, self-adhesive), 3) ACG (artCem GI, conventional), and 4) VAR (Variolink II, conventional). Glass ceramic crowns milled and cemented with dual-polymerized resin cement (Variolink II) served as the control group. The tensile strength was measured initially (n=12) and after aging by mechanical thermocycling loading (1 200 000 cycles, 49 N, 5 degrees C to 50 degrees C) (n=12). The tensile strength (MPa) of all crowns was determined by the pull-off test (Zwick/Roell Z010; Ulm, Germany, 1mm/min). Subsequently, the failure types were classified. Data were analyzed with 2-way and 1-way ANOVA followed by a post hoc Scheffe test and t test (alpha=.05). RESULTS: No adhesion of the tested cements was observed on unconditioned polymeric CAD/CAM crowns and those luted with VAR. Among the tested cements, GCM showed significantly higher values after airborne-particle abrasion with 110 MUm (initial: 2.8 MPa; after aging: 1 MPa) than 50 MUm alumina (initial: 1.4 MPa; after aging: 0 MPa). No significant effect was found between 50 and 110 MUm particle size alumina in combination with the other 2 cements. After aging, the tensile strength of the crowns luted with GCM (50 MUm: 0 MPa and 110 MUm: 1 MPa) and ACG (50 MUm: 1 MPa and 110 MUm: 1.2 MPa) was significantly lower than those luted with RXU (50 MUm: 1.9 MPa and 110 MUm: 2 MPa). All airborne particle abraded polymeric CAD/CAM crowns (initial: 1.4-2.8; 0-2 MPa) showed significantly lower tensile strength values than the control group (initial: 7.3 MPa; after aging: 6.4 MPa). Although with all polymeric specimens, failure type was adhesive between the cement and the crowns, the control group showed exclusively cohesive failures within the ceramic. CONCLUSIONS: Airborne-particle abrasion before cementation of polymeric CAD/CAM crowns minimally improved the tensile strength. Both the failure types and the tensile strength values of adhesively luted glass ceramic crowns showed superior results to adhesively cemented polymeric ones. Although the tensile strength results were low, crowns cemented with RXU showed, after aging, the highest tensile strength of all other tested groups. PMID- 22304744 TI - The effect of phosphoric acid pre-etching and thermocycling on self-etching adhesive enamel bonding. AB - STATEMENT OF PROBLEM: When inserting a resin-bonded prosthesis, it is not known whether pumicing, rinsing, and using a self-etching primer (SE) on prepared surfaces is sufficient or whether the use of an additional conventional acid etchant is warranted due to the increased time and risk of contamination. PURPOSE: The purpose of this study was to evaluate the effects of pre-etching with phosphoric acid (PA) and thermocycling (TC) on the enamel shear bond strength (SBS) of an autopolymerizing adhesive system on ground enamel. MATERIAL AND METHODS: Human teeth were embedded in phenolic rings with methyl methacrylate resin, and their enamel surfaces were ground flat to a 600 grit surface. The teeth were then divided into 4 subsets (n=22): 1) PSN, PA pre-etch with SE, no TC; 2) PST, PA pre-etch with self-etching primer and TC; 3) SEN, self-etching primer alone, no TC; and 4) SET, self-etching primer and TC. A multifactorial study design was used to evaluate 2 factors (pre-etching with PA and TC) at 2 levels (presence or absence) by grouping different subsets. Pre-etch consisted of teeth being etched for 30 seconds with PA, rinsed, re-etched, and rinsed. Self etching consisted of 60 seconds with ED Primer. Rods of Rexillium III, airborne particle abraded with 50 MUm aluminum oxide, were bonded to enamel surfaces with Panavia 21 OP under a 19.6 N load. Thermocycling consisted of alternating between water baths of 5 +/- 2 degrees C and 55 +/- 2 degrees C for 5000 cycles. Shear bond strength (SBS) was determined by loading the specimens to failure at a crosshead speed of 1 mm/min. Mean values were analyzed with a 2-way ANOVA (factors were surface treatment and TC) at alpha=.05. RESULTS: Pre-etching with phosphoric acid showed greater SBS to enamel (P=.028) than the self-etching primer alone. Thermocycling did not have a significant effect (P=.424). CONCLUSIONS: There was a significant difference in SBS between pre-etching enamel surfaces with phosphoric acid in addition to the self-etching primer and using the self-etching primer exclusively. Thermocycling did not significantly affect SBS. PMID- 22304745 TI - Wear of ceramic and titanium ball attachments in subjects with an implant retained overdenture: a controlled clinical trial. AB - STATEMENT OF PROBLEM: Loss of retention of implant-retained overdentures due to wear of the patrix or matrix of the attachment system is a common clinical problem. PURPOSE: The purpose of this controlled clinical trial was to compare the wear of ceramic and titanium ball attachments and their corresponding gold matrices after 1 year of clinical function in subjects with implant-retained mandibular overdentures. MATERIAL AND METHODS: Forty subjects who had been treated with a 2-implant-retained overdenture received either 2 ruby ball attachments (20 subjects) or 2 titanium ball attachments (20 subjects). The diameter of the ball attachments and the thickness of the matrix were measured optically before insertion and after 1 year of clinical function. Differences among groups were then compared with the Wilcoxon rank sum test (alpha=.05). To estimate any correlation between clinical parameters and wear, the Spearman rank test was used. RESULTS: There was no significant difference (P=.73) in the median wear of ball attachments for the titanium group (5.3 MUm; median 1.3 MUm) and for the ceramic group (1.3 MUm; median 1.3 MUm). In the ceramic group, a fracture rate of 30% was observed. The mean wear of the matrices in the titanium group was 3.1 MUm (median 6.8 MUm) and in the ceramic group 2.1 MUm (median 3.4 MUm), P=.01. No correlation was found between ball attachment wear and matrix insert wear (Spearman rank test). Wear of matrices was weakly correlated with an increase in divergence between implant axes in the sagittal plane (P=-.28 and P=.021). Ball attachment wear was associated with an increase in divergence between matrix axes in the sagittal plane (P=-.34 and P=.047). CONCLUSIONS: Matrices on ceramic ball attachments showed less wear than those placed on titanium ball attachments. However, the use of ruby ball attachments cannot be recommended because of a high fracture rate. PMID- 22304746 TI - Cytotoxicity of denture base and hard chairside reline materials: a systematic review. AB - STATEMENT OF PROBLEM: Adverse reactions to the materials used for the fabrication and reline of removable denture bases have been observed. PURPOSE: The purpose of this study was to systematically review the published literature on the cytotoxicity of denture base and hard reline materials. MATERIAL AND METHODS: MEDLINE via PubMed, Google Scholar, and Scopus databases for the period January 1979 to December 2009 were searched with the following key words: (biocompatibility OR cytotoxic* OR allergy OR "burning mouth" OR "cell culture techniques") AND ("acrylic resins" OR denture OR monomer OR relin* OR "denture liners"). The inclusion criteria included in vitro studies using either animal or human cells, in which the cytotoxicity of the denture base and hard chairside reline resins was tested. Studies of resilient lining materials and those that evaluated other parameters such as genotoxicity and mutagenicity were excluded. Articles published in the English language and in peer-reviewed journals focusing on the cytotoxicity of these materials were reviewed. RESULTS: A total of 1443 articles were identified through the search. From these, 20 studies were judged to meet the selection criteria and were included in the review. In the majority of the studies, continuous cell lines were exposed to eluates of specimens made from the materials, and mitochondrial activity was used to estimate cell viability. The tested acrylic resins were grouped according to 5 major categories: (1) heat-polymerized; (2) microwave-polymerized; (3) autopolymerizing; (4) light-polymerized; and (5) hard chairside reliners. CONCLUSIONS: This review provided some evidence that the heat-polymerized resins showed lower cytotoxic effects than autopolymerizing denture base acrylic resins and light or dual polymerized reline resins. However, because of the large number of variables in the reviewed literature, a definitive conclusion could not be drawn. PMID- 22304747 TI - Planning implant positions for an auricular prosthesis with digital data. AB - The esthetic result of an auricular prosthesis is influenced by the position of the prosthesis incorporating the implants. The entire surface of the patient's head is captured by means of a conventional computed tomography (CT). The digital data are used to mirror the contralateral unimpaired ear for restoration of the impaired side. The virtual ear is integrated into a template covering the auricular defect and indexed to the nasal area with computer-aided technology (CAD/CAM). This virtual template is converted into an acrylic resin template. With that the surgeon and the anaplastologist should determine the optimal implant position of the auricular prosthesis. PMID- 22304748 TI - Use of a vinyl polysiloxane (VPS) indicator material to block out proximal undercuts during fabrication of fixed provisional restorations. PMID- 22304749 TI - Template to determine the position and angulation of the abutment screw channel for implant-supported, cement-retained restorations. PMID- 22304750 TI - An alternative direct technique for the fabrication of an implant-supported, screw-retained fixed interim restoration. PMID- 22304751 TI - Bicyclic peptide inhibitor reveals large contact interface with a protease target. AB - From a large combinatorial library of chemically constrained bicyclic peptides we isolated a selective and potent (K(i) = 53 nM) inhibitor of human urokinase-type plasminogen activator (uPA) and crystallized the complex. This revealed an extended structure of the peptide with both peptide loops engaging the target to form a large interaction surface of 701 A(2) with multiple hydrogen bonds and complementary charge interactions, explaining the high affinity and specificity of the inhibitor. The interface resembles that between two proteins and suggests that these constrained peptides have the potential to act as small protein mimics. PMID- 22304752 TI - Synthesis of tunable and multifunctional Ni-doped near-infrared QDs for cancer cell targeting and cellular sorting. AB - Here, we report the facile preparation of tunable magnetic Ni-doped near-infrared (NIR) quantum dots (MNIR-QDs) as an efficient probe for targeting, imaging, and cellular sorting applications. We synthesized the MNIR-QDs via a hot colloidal synthesis approach to yield monodisperse and tunable QDs. These hydrophobic QDs were structurally and compositionally characterized and further functionalized with amino-PEG and carboxyl-PEG to improve their biocompatibility. Since QDs are known to be toxic due to the presence of cadmium, we have evaluated the in vitro and in vivo toxicity of our surface-functionalized MNIR-QDs. Our results revealed that surface-functionalized MNIR-QDs did not exhibit significant toxicity at the concentrations used in the experiments and are therefore suitable for biological applications. For further in vitro applications, we covalently linked folic acid to the surface of amino-PEG-coated MNIR-QDs through NHS chemistry to target the folate receptors largely present in the HeLa cells to demonstrate the specific targeting and magnetic behavior of these MNIR-QDs. Improved specificity has been observed with treatment of HeLa cells with the folic acid-linked amino PEG-coated MNIR QDs (FA-PEG-MNIR-QDs) compared to the one without folic acid. Since the synthesized probe has magnetic property, we have also successfully demonstrated sorting between the cells which have taken up the probe with the use of a magnet. Our findings strongly suggest that these functionalized MNIR-QDs can be a potential probe for targeting, cellular sorting, and bioimaging applications. PMID- 22304753 TI - Preparation and properties of two novel selenoacetic acids: HCF2C(O)SeH and ClCF2C(O)SeH. AB - The novel selenocarboxylic Se-acids, HCF(2)C(O)SeH and ClCF(2)C(O)SeH, were prepared by treating the corresponding carboxylic acids with Woollins' reagent. The boiling points were extrapolated from the vapor pressure curves to be 364 and 359 K for HCF(2)C(O)SeH and ClCF(2)C(O)SeH, respectively. Both compounds are unstable at ambient temperatures and decompose to the corresponding seleno anhydrides and release of H(2)Se. Hydrolysis results in formation of the carboxylic acids and hydrogen selenide, while diselenides presumably are obtained by oxidation. The conformational properties of these acids were studied by vibrational spectroscopy in combination with ab initio and DFT methods. IR vapor phase spectra, Raman spectra of the neat liquids, and IR spectra of the Ar matrix-isolated compounds deposited at two different nozzle temperatures were interpreted in terms of quenching conformational equilibria. The most stable structure of both acids was found to be syn-gauche in equilibrium with a second anti-syn form in HCF(2)C(O)SeH and with another two conformers, anti-gauche and anti-syn, in ClCF(2)C(O)SeH. PMID- 22304754 TI - Inactivation of the central nucleus of the amygdala reduces the effect of punishment on cocaine self-administration in rats. AB - Continued cocaine use despite the negative consequences is a hallmark of cocaine addiction. One such consequence is punishment, which is often used by society to curb cocaine use. Unfortunately, we know little about the mechanism involved in regulation by punishment of cocaine use. The fact that cocaine addicts continue to use cocaine despite potentially severe punishment suggests that the mechanism may be impaired. Such impairment is expected to critically contribute to compulsive cocaine use. This study was aimed at testing the hypothesis that the central nucleus of the amygdala (CeN) plays a critical role in such regulation. To this end, rats were trained to press a lever to self-administer cocaine under a chained schedule: a response on one lever (cocaine-seeking lever) led to access to the other lever (cocaine-taking lever), on which a response was reinforced by cocaine and cues. Thereafter, responses on the seeking lever were punished by footshock with a probability of 0.5. Cocaine self-administration (SA) was significantly suppressed by punishment in an intensity-dependent manner. Interestingly, rats trained with daily 6-h (extended access) but not 2-h (limited access) sessions showed resistance to the lower intensity of punishment. Inactivation of the CeN induced a robust anti-punishment effect in both groups. These data provided evidence that the CeN is a critical neural substrate involved in regulation by punishment of cocaine SA. Rats with a history of extended cocaine SA appeared to be less sensitive to punishment. The decreased sensitivity could result from the neuroplastic changes induced by extended cocaine SA in the CeN. PMID- 22304755 TI - Identification of the product of toxoflavin lyase: degradation via a Baeyer Villiger oxidation. AB - Toxoflavin (an azapteridine) is degraded to a single product by toxoflavin lyase (TflA) in a reaction dependent on reductant, Mn(II), and oxygen. The isolated product was fully characterized by NMR and MS and was identified as a triazine in which the pyrimidine ring was oxidatively degraded. A mechanism for toxoflavin degradation based on the identification of the enzymatic product and the recently determined crystal structure of toxoflavin lyase is proposed. PMID- 22304756 TI - MS/MS library facilitated MRM quantification of native peptides prepared by denaturing ultrafiltration. AB - Naturally occurring native peptides provide important information about physiological states of an organism and its changes in disease conditions but protocols and methods for assessing their abundance are not well-developed. In this paper, we describe a simple procedure for the quantification of non-tryptic peptides in body fluids. The workflow includes an enrichment step followed by two dimensional fractionation of native peptides and MS/MS data management facilitating the design and validation of LC- MRM MS assays. The added value of the workflow is demonstrated in the development of a triplex LC-MRM MS assay used for quantification of peptides potentially associated with the progression of liver disease to hepatocellular carcinoma. PMID- 22304757 TI - [Clinical investigation of Spanish Internal Medicine in Europe (1997-2009)]. PMID- 22304758 TI - [Renal function in patients with heart failure: prognostic value]. AB - INTRODUCTION: Impaired renal function can lead to a poor prognosis in patients with heart failure (HF). This study analyses the prevalence and prognostic value of impaired renal function in a cohort of patients with HF. METHODS: We analysed patients who were included in the RICA study (multicentre, prospective cohort study) who were admitted for decompensated HF in 52 Spanish Internal Medicine Departments between March 2008 and September 2009. The patients were grouped according to their renal function, evaluated by eGF, using the MDRD formula. RESULTS: A total of 714 patients (54% women) with a mean age of 77.3+8.7 years were included. Of these, 84% had hypertension, and hypertensive heart disease was the most common aetiology of HF (39.2%). Ejection fraction was normal in 64.7% of patients, and 59.5% had an eGF less than 60 mL/min per 1.73 m(2), and 11.2% with an eGF less than 30 mL/min per 1.73 m(2). Less spironolactone was prescribed in patients with advanced stages of renal dysfunction (24%), compared with patients with an eGF>60 mL/min/1.73 m(2) (35%; P=.025). Worsening renal function was independently associated with an increased mortality risk (RR: 2.05; 95% CI: 1.13 3.71; P=.018). CONCLUSIONS: About 60% of patients admitted to Internal Medicine with HF have impaired renal function. This comorbidity is associated with a two fold increase in all-cause mortality. PMID- 22304759 TI - Informant-reported cognitive symptoms that predict amnestic mild cognitive impairment. AB - BACKGROUND: Differentiating amnestic mild cognitive impairment (aMCI) from normal cognition is difficult in clinical settings. Self-reported and informant-reported memory complaints occur often in both clinical groups, which then necessitates the use of a comprehensive neuropsychological examination to make a differential diagnosis. However, the ability to identify cognitive symptoms that are predictive of aMCI through informant-based information may provide some clinical utility in accurately identifying individuals who are at risk for developing Alzheimer's disease (AD). METHODS: The current study utilized a case-control design using data from an ongoing validation study of the Alzheimer's Questionnaire (AQ), an informant-based dementia assessment. Data from 51 cognitively normal (CN) individuals participating in a brain donation program and 47 aMCI individuals seen in a neurology practice at the same institute were analyzed to determine which AQ items differentiated aMCI from CN individuals. RESULTS: Forward stepwise multiple logistic regression analysis which controlled for age and education showed that 4 AQ items were strong indicators of aMCI which included: repetition of statements and/or questions [OR 13.20 (3.02, 57.66)]; trouble knowing the day, date, month, year, and time [OR 17.97 (2.63, 122.77)]; difficulty managing finances [OR 11.60 (2.10, 63.99)]; and decreased sense of direction [OR 5.84 (1.09, 31.30)]. CONCLUSIONS: Overall, these data indicate that certain informant-reported cognitive symptoms may help clinicians differentiate individuals with aMCI from those with normal cognition. Items pertaining to repetition of statements, orientation, ability to manage finances, and visuospatial disorientation had high discriminatory power. PMID- 22304760 TI - Are there trade-offs between pre- and post-fledging survival in black brent geese? AB - 1. The growth period is an important determinant of fitness later in life through its effects on first-year survival and future reproduction. Choices by adult females about where to rear their offspring strongly affect growth rates and offspring fitness in geese. 2. Individual female black brent (Branta bernicla nigricans) tend to raise their broods in the same areas each year, and these areas are consistently ranked with respect to growth rates of goslings. Therefore, some females consistently rear their broods on areas resulting in lower post-fledging fitness. 3. We explore the potential that growth rates of offspring (and associated fitness consequences) are traded off against other vital rates influencing fitness of either adult females or goslings. Growth of goslings primarily influences fitness after fledging, so one hypothesis is that survival before fledging, which is influenced by predation, is traded off against growth rates and post-fledging survival. 4. We estimated pre-fledging and post fledging survival for goslings reared on areas used by broods from the Tutakoke River black brent colony. We examined recaptures, recoveries by hunters and resightings of brent marked as goslings with webtags and standard leg rings. These data were analyzed using capture-mark-recapture models in program mark to derive separate estimates of pre- and post-fledging survival for 18 cohorts (1987 2004) of black brent goslings across seven brood rearing areas (BRAs). 5. Estimates of pre-fledging survival probability varied from 0.00 +/- 0.00 (mean +/ 95% confidence interval) to 0.92 +/- 0.1; and estimates of post-fledging survival probability varied from 0.00 +/- 0.00 to 1.00 +/- 0.08. Substantial variation existed both among BRAs and years but post-fledging survival declined substantially during the study. 6. Pre- and post-fledging survival were positively correlated, exhibiting a quadratic relationship (beta(post-fledging survival) = 1.00 (+/-0.47)x-0.83 (+/-0.480)x(2) , where x = pre-fledging survival). Therefore, we did not find a trade-off between pre- and post-fledging survival in black brent goslings across BRAs, suggesting that factors other than foraging conditions and predation on goslings must influence selection of BRAs. PMID- 22304761 TI - Chronic bradykinin treatment alters 1alpha,25-dihydroxyvitamin D3-induced calcium current modulation in pre-osteoblasts. AB - Bradykinin (BK) is involved in bone resorption in chronic inflammatory diseases. During bone formation, 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) plays an important role in the regulation of Ca2+. In osteoblasts, 1,25(OH)2D3 stimulates transmembrane influx of Ca2+ through voltage-sensitive Ca2+ channels (VSCCs). Voltage sensitive Ca2+ channels serve as crucial mediators of membrane excitability and many Ca2+-dependent functions, including bone growth, regulation of proliferation, enzyme activity and gene expression. The purpose of this study was to investigate the effects of BK and 1,25(OH)2D3 on VSCC currents carried by Ba2+ (IBa). Application of 1,25(OH)2D3 facilitated IBa in a voltage-dependent manner. Pretreatment with SQ22536 (an adenylate cyclase inhibitor) attenuated 1,25(OH)2D3-induced facilitation of IBa. Bradykinin and BK1 receptor agonist [Lys des-Arg9]-BK also facilitated IBa. After 24 h or 7 days exposure to BK, that is, under chronic inflammatory conditions, application of 1,25(OH)2D3 inhibited IBa. In addition, pretreatment with PD98,059, a mitogen-activated protein kinase (MAPK) tyrosine kinase inhibitor, attenuated 1,25(OH)2D3-induced inhibition of IBa. These results indicate that, under normal conditions, 1,25(OH)2D3 acts with adenylate cyclase to facilitate VSCCs, whereas under chronic inflammatory conditions it acts with MAPK to inhibit VSCCs in pre-osteoblasts. PMID- 22304762 TI - Prevalence and risk factors of astrovirus infection in puppies from French breeding kennels. AB - Aiming at determining the prevalence and the risk factors associated to astrovirus infection in puppy, fecal samples were collected in 316 puppies (age from 5 to 14 weeks of age) from 33 French breeding kennels. Data were registered for each puppy, including age, breed, gender, origin of the dog, and feces quality. The samples were tested by specific RT-PCR for the presence of canine astrovirus. Astroviruses were identified in 20.9% (66/316) of the puppies and in 42% (14/33) of the breeding kennels. Young puppies (i.e. <7 weeks of age) and puppies from large breeding kennels were more likely to be infected by the astrovirus. No association between the quality of feces and astrovirus infection could be determined in this survey. PMID- 22304763 TI - [Immune response to HBsAg can not be enhanced with B7-H1 protein vaccine]. AB - AIM: To observe the immunization effect to HBsAg by B7-H1 protein vaccine in transgenic mice, and to explore new methods for the treatment of chronic hepatitis B. METHODS: After the joint immunization in HBV transgenic mice with different doses of hepatitis B virus (HBV) vaccine and B7-H1 protein, the anti-B7 H1 antibody titors, Th1 type of cytokines (IFN-gamma and IL-2) from the spleen cells of mice, the number of the T cells secreting IFN-gamma and the number of the mice lymphocyte proliferation were measrued by ELISA, ELISPOT and MTT technique respectively, to compare the immune effect of different immune methods and regimen. RESULTS: The immune plans were completed successfully. The anti-B7 H1 antibody was detected in the fifth week after immunization with B7-H1 vaccine, at the same time no obvious difference of antibodies titors between groups were found. IL-2 and the number of T cells secreting IFN-gamma were significantly reduced(P<0.05)in joint immunization group with B7-H1 protein and HBsAg, but no difference in other immune tests, such as IFN-gamma, lymphocyte proliferation. CONCLUSION: A lower doses of HBsAg can cause the secretion of Th1 type of cytokines and lymphocyte proliferation. B7-H1 protein vaccines have a better immunogetic effect for HBV transgenic mice, but can notupregulate the immune response to HBsAg. PMID- 22304764 TI - [Expression, purification and protective antigen analysis of cell wall protein MRP of Streptococcus suis type 2]. AB - AIM: To amplify the mrp gene of Streptococcus suis type 2 05ZYH33, express it in E.coli BL21 in order to acquire high purity recombinant protein MRP, then evaluate the protective antigen of recombinant protein MRP. METHODS: Using PCR technology to obtain the product of mrp gene of 05ZYH33, and then cloned it into the expression vector pET28a(+). The recombinant protein was purified by affinity chromatography, later immunized New Zealand rabbit to gain anti-serum, then test the anti-serum titer by ELISA. The opsonophagocytic killing test demonstrated the abilities of protective antigen of MRP. RESULTS: The truncated of MRP recombinant protein in E.coli BL21 expressed by inclusion bodies, and purified it in high purity. After immunoprotection, the survival condition of CD 1 was significantly elevated. The survival rate of wild-type strain 05ZYH33 in blood was apparently decreased after anti-serum opsonophagocyticed, but the mutant delta; MRP showed no differences. CONCLUSION: MRP represent an important protective antigen activity. PMID- 22304765 TI - [Expression, purification and activity identification of ZtaN-p23 fusion protein in Escherichia coli of Epstein-Barr virus]. AB - AIM: To construct the prokaryotic expression plasmid pGEX-4T-1-BZLF1N-BLRF2, and express it in Escherichia coli. METHODS: The EB virus BZLF1N gene and BLRF2 gene were amplified by RT-PCR respectively. Then, the two genes were linked by splicing overlap extension PCR method and inserted into the vector pGEX-4T-1, and the recombinant plasmid pGEX-4T-1-BZLF1N-BLRF2 was transformed into E.coli BL21 (DE3) strain. The expression protein ZtaN-p23 was analysed by SDS-PAGE and immunoreactivity was proved by Western blotting. RESULTS: Restriction enzyme digestion and DNA sequencing showed recombinant plasmid constructed successfully. The expression product ZtaN-p23 with the molecular weight 46000 was located in the cytoplasm and insoluble. The ZtaN-p23 up to 95% purity was obtained after purified using affinity chromatography. Western blotting showed fusion protein possessed a well bioactivity and specificity. CONCLUSION: The fusion gene BZLF1N BLRF2 is successfully constructed and effectively expressed in E.coli, which lay the foundation for further research on its biological properties and functions. PMID- 22304766 TI - [Molecular cloning and preliminary functional study of TRBP]. AB - AIM: Construct prokaryotic expression vector carrying mouse TRBP (TAR RNA-binding protein) gene and test the double-stranded RNA binding ability of TRBP. METHODS: RT-PCR was used to obtain TRBP cDNA from mouse genomic DNA. Then, we built the His-tag fusion expression vector of TRBP and transformed it into E.coli BL21(DE3). Ni-NTA beads were used to isolate and purify the recombinant protein and vitro transcription was used to get Pre-miR-122. Finally, SDS-PAGE and ITC (isothermal titration calorimetry) assay were both used to validate TRBP's binding ability with Pre-miR-122. RESULTS: We purified the recombinant protein TRBP whose molecular weight is 32.4 kDa. The purified bioactive TRBP protein binding on NI-NTA beads showed that it had a strong binding capacity on Pre-miR 122. CONCLUSION: We constructed TRBP prokaryotic expression system successfully and studied the double-stranded RNA binding ability of TRBP preliminarily. PMID- 22304767 TI - [Effect of superantigen SEA on mitochondrial membrane potential of Molt-4 cell]. AB - AIM: To explore the effect of superantigen staphylococcal enterotoxin A(SEA) on mitochondrial membrane potential of Molt-4 cell. METHODS: Cell counting kit-8(CCK 8) was used to detect the proliferation of T cell in different concentration and time, We employed JC-1 to estimate mitochondrialmembrane potential (deltapsim) of Molt-4 cell induced by SEA using flow cytometry (FCM). RESULTS: The proliferative activity of T cell treated with SEA(1 mg/L) was changed obviously compared with control.The mitochondrial membrane potential of Molt-4 cell with SEA(1 mg/L) was highest at 10 min by FCM after stimulation of 180, 60, 30 and 10 min. Mitochondrial membrane potential of Molt-4 cell treated with SEA after 10 and 30 min were lower than that with PHA which also have rising effect. CONCLUSION: Superantigen can enhance the mitochondrial membrane potential of Molt 4 cell in the early stage of proliferation.But the effect was weaker than that with mitogen PHA. PMID- 22304768 TI - [Changes and effects of significant membrane molecules on thymic T cell of aging mice induced by D-galactose]. AB - AIM: To establish subacute aging mice model by D-galactose and to explore the changes and effects of significant membrane molecules on thymic T cell. METHODS: Female Kunming mice of 8 weeks old were injected with D-galactose of 12.5 mL/(kg.d) by subcutaneous in scruff for 42 days. The animals' living conditions and biological behaviors were observed everyday.SOD activities and MDA content of serum were measured to determine whether the aging model was successfully established.On the basis of successfully establishing aging model, detect the significant membrane molecules of thymic T cell by Immunofluorescence technique and Flow Cytometer. RESULTS: During the 42 days, gradually, the model mice showed bending body, loose skin, slow action and so on.The activities of SOD in the serum were significantly decreased(P<0.01), and the content of MDA in the serum was significantly increased(P<0.01). The thymic naive T cell significant molecule, CD45RA was decreased(P<0.05). T cell activation-related molecules, CD28 and CD25 were both decreased(P<0.05), and PD-1 was significantly increased(P<0.01). The memory T cell significant molecule, CD196 was increased, but was not significantly compared to the control mice. CONCLUSION: The D galactose subacute aging mice model was successfully established.The naive and active T cell were decreased and the memory T cell was increased in the thymic of the aging. PMID- 22304769 TI - [The changes of spleen B cells of D-galactose-induced aging mice]. AB - AIM: This paper is to analyze the changes of important membrane type molecules of the spleen B cells and their significance on the basis of biology identification by establishing subacute aging mice model with D-galactose. METHODS: Health Kunming mice are injected with 100 ng/L D-galactose, 0.25 mL/20 g, once per day, for 42 days consecutively, into their back necks. The animals' living conditions and biological behaviors are observed everyday and the dynamic changes of their weight are measured regularly. The biology identification of aging model mice is conducted by means of measuring the SOD viability and malondialdehyde (MDA) concentration in serum; the analysis of the activation- and memory-related important membrane type molecules of spleen cells is carried out with immune fluorescence and flow cytometry; the analysis of the concentration of IL-4 in serum is conducted by ELISA. RESULTS: Building a successful subactue aging mice model.The results of immune fluorescence and flow cytometry showed that CD20(+); was 56.8%, CD40(+); was 43.6%, CD20(+);CD45RA(+);B was 14.04%, CD40(+);CD45RA(+);B was 35.4%, CD20(+);CD86(+);B was 2.25%, CD40(+);CD86(+);B was 4.38%, CD20(+);CD196(+);B was 10.68%, and CD40(+);CD196(+);B was 10.98%. The results of ELISA showed that the average level of IL-4 in serum was 7.93 ng/L. The statistical analysis showed that the expressions of CD20, CD40, CD45RA, and CD86 of the spleen cells of the model control group and the average level of IL-4 in serum were lower than the normal control group(P<0.05)while CD196 was higher than the normal control group(P<0.01). CONCLUSION: In the body's aging process, the expressions of the activation- and memory-related important membrane type molecules of spleen cells change, activated cells reduce, memory cells increase, and the expression of IL-4 in serum drop, resulting in the immune system function disorder. PMID- 22304770 TI - [The mechanism of polypeptide derived from viral macrophage inflammatory protein II modulates SDF-1alpha/CXCR4-induced migration]. AB - AIM: To assess whether NT21MP, the synthetic antagonist 21-mer peptide derived from viral macrophage inflammatory protein II inhibits human SKBR3 cells migration by interfering with SDF-1alpha/CXCR4 signaling. METHODS: The levels of CXCR4 were detected in breast cancer cells SKBR3 and MCF-7 by RT-PCR and immunohistochemistry. The effect of SDF-1alpha-induced SKBR3 migration (chemotaxis) in the presence and absence of NT21MP was determined using the Boyden chamber migration assay. Intracellular Ca(2+); concentration was measured by fluorometric analysis. Western blot analyses were performed to quantify phosphorylated ERK1/2 and FAK expression levels. RESULTS: The expression of CXCR4 was higher in SKBR3 than MCF-7 cells; SKBR3 migration increased in SDF-1alpha treated cells. In contrast, AMD3100, an inhibitor of CXCR4 effectively inhibited SKBR3 migration. SKBR3 migration was decreased when the cells were exposed to NT21MPdose dependently(P<0.05). NT21MP also blocked Ca(2+); influx(P<0.05), an important signal for SKBR3 migration. In addition, NT21MP significantly decreased SDF-1alpha-induced SKBR3 migration and downregulated SDF-1alpha-induced express of phospho-ERK1/2 and phospho-FAK(P<0.05). CONCLUSION: The results showed that NT21MP has an inhibitory effect on SDF-1alpha-induced SKBR3 migration. The plausible mechanism of action could be upstream blockage of Ca(2+); influx and the downstream reduction of ERK1/2 and FAK signals. PMID- 22304771 TI - [Construction of eukaryotic plasmid of human hCAP gene and the expression and localization of fusion protein]. AB - AIM: To construct the expression plasmid of human c-Cbl-associated protein (hCAP) gene and identify the expression and localization of fusion protein. METHODS: Total mRNA was extracted from CV-1 cells, and cDNA was formed by reverse transcription. The hCAP coding sequence was amplified by polymerase chain reaction (PCR) and cloned into pEGFP-C1 plasmid. After the hCAP gene was identified by enzyme digestion and sequencing, the plasmid was transfected into COS-7 cells. The expression of the recombinant plasmid in COS-7 cells was detected by Western blot assay. The localization of pEGFP-hCAP in NIH3T3 cells was observed with laser confocal microscopy. RESULTS: hCAP was successfully constructed into the pEGFP-C1 expressing vector. The length of the fragment identified by restriction enzyme digestion was 3 879 bp. The expression of pEGFP hCAP fusion protein with a molecular weight of 169kDa was detected by Western blot. The pEGFP-hCAP fusion protein was mostly localized at the cell periphery of NIH3T3 cells. CONCLUSION: The recombinant plasmid of hCAP gene was successfully cloned into eukaryotic expressing vector, and the pEGFP-hCAP fusion protein was mostly localized at the cell periphery of NIH3T3 cells. PMID- 22304772 TI - [Construction and identification of recombinant adenovirus vector containing siRNA for rat TLR2 gene]. AB - AIM: To construct the recombinant adenovirus vector containing specific small interfering RNA (siRNA) targeting rat TLR2 gene and identify its function in PC12 cells. METHODS: Three pairs of double-stranded DNA fragments for silencing rat TLR2 were annealed in vitro, then directional cloned into the pSES-HUS vector to construct pSES-HUS-siTLR2 plasmid. Afterward, the correct recombinant was linearized by PmeI, following co-transformation with the backbone vector pAdEasy 1 in E.coli BJ5183 to construct pAd-siTLR2 plasmid, and then transfected into HEK293 cell line via Lipofectamine to package the adenovirus. PC12 cells were infected with the adenovirus Ad-siTLR2, and inhibition of siRNA was detected with Real-time PCR and Western blotting. RESULTS: Using plasmid PCR and gene sequencing, the siTLR2 target gene was verified to be correctly cloned in the adenovirus vector. Trough Real-time PCR and Western blotting, TLR2 expression was significantly decreased in the PC12 cells which was infected with the adenovirus Ad-siTLR2. CONCLUSION: Successfully constructed the recombinant adenovirus vector containing rat siTLR2 gene and packaged the adenovirus in HEK293 cell line, which could effectively reduce TLR2 expression in the PC12 cells to facilitate the study of the immunoregulation mechanisms of TLR2 in different diseases. PMID- 22304773 TI - [Antitumoral efficacy by systemic delivery of cationic liposome-plasmid interleukin-15 complexes in murine models of lung metastasis]. AB - AIM: To investigate the therapeutic effect of the plasmid pcDNA3.1-IL15 complexed with cationic liposome (CL-IL15) in the B16-F10 melanoma lung metastasis model. METHODS: A plasmid with high secretive efficiency of IL-15 was constructed and the optimum mix ratio was determined to formulate cationic liposome-plasmid complex with the optimal encapsulation. The CHO-K1 cell line was transfected by CL-IL15. The secretion of transfected IL-15 gene was detected by Western blot and its biological function was measured through the proliferation response of CTLL-2 cytotoxic T cell line of murine by MTT assay. The C57BL/6 mice were inoculated intravenously (i.v.) with B16-F10 melanoma lung metastasis cells then treated (i.v.) by CL-IL15 in a therapeutic setting to determine the tumorigenesis and research the corresponding mechanisms. RESULTS: The pcDNA3.1-IL15 plasmid was successfully constructed and the mass-ratio of optimal condition of cationic liposome-plasmid with perfect entrapment was 1:5 (plasmid: cationic liposome). Western blot analysis displayed the detection of IL-15 both in the medium and the pcDNA3.1-IL15 transfected cells. MTT assay showed that CTLL-2 cells could proliferate with the medium obtained from CHO-K1 cells transfected by CL-IL15. And the administration of CL-IL15 complexes led to the significant inhibition lung metastasis of malignant melanoma (P<0.05). CONCLUSION: CL-IL15 could inhibit the metastasis of malignant melanoma and the cationic liposome delivered plasmid pcDNA3.1-IL-15 complexes may be an efficient therapeutic strategy for the treating of lung metastasis. And the effective splenic cell-mediated cytotoxicity and the obvious NK cells recruitment may be involved. PMID- 22304774 TI - [Construction of a recombined adenovirus vector carrying pri-miR-21 gene and research on it's target gene TLR4]. AB - AIM: To construct the recombined adenovirus vector carrying pri-miR-21 gene, which can express mature miR-21 efficiently, and to study the interaction of miR 21 with its target gene TLR4. METHODS: Using healthy mouse's gDNA as template, the primary miR-21 coding sequence was amplified by PCR and cloned into a shuttle vector pAdTrack-CMV. Constructed plasmid was sequenced and linearized for homologous recombination with pAdEasy-1 vector in BJ5183 bacteria. The recombined adenovirus vector carrying pri-miR-21 gene was used to challenge HeLa cell. The candidate target gene of miR-21 was determined by miRNA analysis databases. The expression level of TLR4 protein was detected by western blotting. RESULTS: Through the PCR, restriction enzyme digestion, DNA sequencing and expression of GFP, recombinant adenoviral vector pri-miR-21 gene was constructed successfully. Bioinformatic analysis suggested a few possible binding sites between miR-21 and TLR4. Results showed that miR-21 down-regulated TLR4 at protein levels. CONCLUSION: The recombinant adenoviral vector containing pri- miR-21 was successfully constructed. miR-21 gene interfered with the expression of TLR4 target gene. PMID- 22304775 TI - [Effects of 1, 25(OH)(2);D(3); on parathyroid hormone induced transdifferentiation and TGF-beta(1); expression in cultured human renal tubular epithelial cells]. AB - AIM: To explore the effects of 1, 25(OH)(2);D(3); on parathyroid hormone (PTH) induced transdifferentiation and TGF-beta(1); expression in cultured human renal tubular epithelial cells. METHODS: HK-2 cells were cultured in DMEM/F12 medium supplemented with 50 mL/L FBS. Cells were divided into three groups. (1) CONTROL GROUP: without PTH or 1, 25(OH)(2);D(3);; (2) PTH group: 10(-10); mol/L PTH; (3) PTH and 1, 25(OH)(2);D(3); group: 10(-10); mol/L PTH and different concentrations of 1, 25(OH)(2);D(3); (10(-10);, 10(-9);, 10(-8); and 10(-7); mol/L). The gene expressions of alpha-SMA and TGF-beta(1); were detected by semi quantitative RT-PCR. The protein expressions of alpha-SMA and TGF-beta(1); were detected by Western blot. Immunocytochemisty (ICC) was used to measure the expression of alpha-SMA in HK-2. ELISA was used to assay the level of TGF beta(1); in the supernatant. RESULTS: The gene expressions of alpha-SMA and TGF beta(1); in PTH group were significantly higher than those in control group (P<0.05). In contrast, they were significantly lower in PTH and 1, 25(OH)(2);D(3); group than those in PTH group (P<0.05). Western blot results showed alpha-SMA could not be detected in normal HK-2 cells, which could be detected in PTH group. TGF-beta(1); protein expression in PTH group was higher than that in control group. In PTH and 1, 25(OH)(2);D(3); group, alpha-SMA and TGF-beta(1); protein expressions were significantly lower than those in PTH group (P<0.05). ICC results showed that alpha-SMA was hardly expressed in cells of control group. However, positive expression of alpha-SMA could be seen in many cells in PTH group. In PTH and 1, 25(OH)(2);D(3); group, the cells of alpha-SMA positive expressed were significantly less than those in PTH group (P<0.05). ELISA results showed that the level of TGF-beta(1); in the supernatant of PTH group was higher than that in control group, which was also higher than that in PTH and 1, 25(OH)(2);D(3); group (P<0.05). CONCLUSION: 1, 25(OH)(2);D(3); can attenuate PTH-induced transdifferentiation and TGF-beta(1); expression in cultured human renal tubular epithelial cells. PMID- 22304776 TI - [Zinc finger protein designed to hepatitis B virus core promoter inhibit the transcription of HBV in HepG2.2.15 cells]. AB - AIM: To observe the inhibition of hepatitis b virus(HBV) transcription in vitro by zinc fingrer protein(ZFP) which was designed specifically to bind DNA sequence in the HBV core promoter(Cp). METHODS: The sequence of HBV Cp was submitted to the Zinc Finger Tools and selected a sequence from the Cp as the target site of ZFP. The nucleic acid sequence of ZFP was synthesised and cloned into pEGFP-N1 or pcDNA3.1(+) to construct the recombinant plasmid pEGFP-N1/ZFP-Flag or pcDNA3.1(+)/ZFP. COS-7 cells were transfected with pEGFP-N1 or pEGFP-N1/ZFP-Flag, the expression of ZFP was observed by green fluorescent microscope, RT-PCR and Western blot. HepG2.2.15 cells were transfected with pcDNA3.1(+) or pcDNA3.1(+)/ZFP, HBeAg and HBV DNA levels in cell supernatant were detected by ELISA and FQ-PCR, HBV mRNA was tested by RT-PCR. RESULTS: ZFP can express in COS 7 cells.In th presence of ZFP, HBeAg expression and HBV DNA level was significantly reduce(P<0.05), and HBV mRNA was dramatically decreased. CONCLUSION: ZFP can express in eukaryotic cells and inhibit the transcription of HBV in vitro. PMID- 22304777 TI - [Effect of IL-17 on the expression of monocyte chemoattractant protein-1 in the cardiac myocytes]. AB - AIM: To investigate the effect of interleukin-17 (IL-17) on the expression of monocyte chemoattractant protein-1(MCP-1) in the primary cultured cardiac myocytes. METHODS: The cardiac myocytes were isolated from neonatal mice by different adhesion method. The expressions of IL-17R and MCP-1 in the cardiac myocytes were evaluated by reverse transcription-polymerase chain reaction (RT PCR). And the concentration of MCP-1 in the culture supernatant of the cardiac myocytes was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: There was the expression of IL-17R in the cardiac myocytes. After stimulated by IL-17, the expressions of MCP-1 in the cardiac myocytes were significantly increased in dose-dependent manner compared with that of culture medium control (P<0.05). The amount of MCP-1 mRNA in the cardiac myocytes was the highest at 4 h after stimulated by IL-17. And then the amount of MCP-1 mRNA in the cardiac myocytes began to descend. The concentrations of MCP-1 in the culture supernatant of the cardiac myocytes increased in time-dependent manner and had significant differences with the control group (P<0.05). CONCLUSION: The cardiac myocytes could express IL-17R. IL-17 could up-regulate the expression of MCP-1 in the cardiac myocytes, which was associated with the dose and stimulation time of IL-17. PMID- 22304778 TI - [Preparation of polyclonal antibody and prokaryotic expression of recombinant protein RelA from Mycobacterium tuberculosis]. AB - AIM: To prepare polyclonal antibodies against RelA protein of Mycobacterium tuberculosis. METHODS: RelA gene segment was inserted into pET-32a(+) and the recombinant protein RelA was expressed in E.coli under IPTG induction.The protein was purified and identified by SDS-PAGE and Western blot.Polyclonal antibody to RelA was got by immunizing rabbits with the protein. Quality and quantity of the antibody was identified. RESULTS: RelA gene segment was successfully inserted into pET-32a(+) and recombinant protein RelA was obtained.The polyclonal antibody to RelA had a good specificity, and the titer reached more than 1:6 400. CONCLUSION: RelA recombinant protein and rabbit anti-RelA polyclonal antibody with high specificity were obtained, which provided good tools for further studying functional characterization of RelA. PMID- 22304779 TI - [Detect the PES1 expression with prepared monoclonal antibody]. AB - AIM: To prepare anti-PES1 monoclonal antibody (mAb) and detect the PES1 expression in several kinds of human cancer cell lines and its tissue distribution in the adult rat. METHODS: pGEX-PES1(1-322aa) fusion protein was purified and inject-ed into mice for immunization. Anti-PES1 mAb was produced by cell fusion and screening after immunization. Anti-PES1 mAb was identified by Western blot. Several human cancer cell lines and different tissue samples of adult rat were detected the PES1 expressions with the mAb prepared. RESULTS: Aanti-PES1 mAb was determined to be specific to PES1 with Western blot analysis. PES1 were expressed in all kinds of breast, ovary, liver and lung cancer cell lines detected in different levels with prepared mAb. Pescadillo was obviously expressed in the breast and ovary but not other tissues of adult rat using prepared mAb. CONCLUSION: Anti-PES1 mAb was successfully prepared. PES1 may play an important role in the tumorigenicity and may also play a role in the pathway of estrogen since breast and ovary, the most important estrogen target organ of adult rat, obviously express pesca-dillo. PMID- 22304780 TI - [Preparation and partial characterization of monoclonal antibodies against HA protein of H1 subtype influenza virus]. AB - AIM: Preparation of H1 subtype of influenza virus HA protein monoclonal antibody (mAbs), and to analyse their reactivity. METHODS: H1N1 influenza virus vaccine (2009) and seasonal A1 influenza virus vaccine as antigen, conventional immunization, fusion, cloning, access to the antigen-specific mAbs. To study the reactivity and specificity of mAbs by ELISA, HI test and Western blot. RESULTS: We have obtained 97 hybridoma of stable secreting anti-H1 subtype of influenza virus HA protein. According to their different reactivity, these mAbs can be divided into four categories: 39 strains for strain-specific, of which 29 have HI activity; 7 strains for subtype-specific, of which 5 have HI activity; 16 strains for the 2009 pandemic strain and the seasonal strains to common antigens, of which 9 have HI activity; 35 strains common for influenza virus antigens, of which 22 have HI activity. CONCLUSION: Both vaccines have better immunogenicity and immune protection activity. Preparation of four types antibody against HA protein of H1 subtype of influenza virus, can provide experimental data for preparation subtype-specific diagnostic kits and influenza A and B virus diagnostic kit, and lay a foundation for further studying of H1N1 influenza virus HA epitope. PMID- 22304781 TI - Fifty ways to reduce length of stay: an inventory of how hospital staff would reduce the length of stay in their hospital. AB - PURPOSE AND SETTING: In this study we present a bottom up approach to developing interventions to shorten lengths of stay. Between 1999 and 2009 we applied the approach in 21 Dutch clinical wards in 12 hospitals. We present the complete inventory of all interventions. DESIGN: We organised, on the hospital ward level, structured meetings with the staff in order to first identify barriers to reduce the length of stay and then later to link them to interventions. The key components of the approach were a benchmark with the fifteenth percentile and the use of a matrix, that on one side was arranged along the main phases of the care process--the admission, stay and discharge--and on the other side to the degree to which the length of stay could be shortened by the medical specialists and nurses themselves or by involving others. FINDINGS AND CONCLUSIONS: The matrix consists of a wide variety of interventions that mainly cover what we found in published research. As a bottom up approach is more likely to succeed, we would advise wards that have to reduce length of stay to make the inventory themselves, using appropriate benchmark data, and by using the matrix. PMID- 22304782 TI - Melioidosis in animals, Thailand, 2006-2010. AB - We retrospectively estimated the incidence of culture-proven melioidosis in animals in Thailand during 2006-2010. The highest incidence was in goats (1.63/100,000/year), followed by incidence in pigs and cattle. The estimated incidence of melioidosis in humans in a given region paralleled that of melioidosis in goats. PMID- 22304783 TI - 3D-QSAR studies on the inhibitory activity of trimethoprim analogues against Escherichia coli dihydrofolate reductase. AB - Three-dimensional quantitative structure activity relationship (3D-QSAR) study has been carried out on the Escherichia coli DHFR inhibitors 2,4-diamino-5 (substituted-benzyl)pyrimidine derivatives to understand the structural features responsible for the improved potency. To construct highly predictive 3D-QSAR models, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods were used. The predicted models show statistically significant cross-validated and non-cross-validated correlation coefficient of r2 CV and r2 nCV, respectively. The final 3D-QSAR models were validated using structurally diverse test set compounds. Analysis of the contour maps generated from CoMFA and CoMSIA methods reveals that the substitution of electronegative groups at the first and second position along with electropositive group at the third position of R2 substitution significantly increases the potency of the derivatives. The results obtained from the CoMFA and CoMSIA study delineate the substituents on the trimethoprim analogues responsible for the enhanced potency and also provide valuable directions for the design of new trimethoprim analogues with improved affinity. PMID- 22304784 TI - Discrimination of gender-, speed-, and shoe-dependent movement patterns in runners using full-body kinematics. AB - Changes in gait kinematics have often been analyzed using pattern recognition methods such as principal component analysis (PCA). It is usually just the first few principal components that are analyzed, because they describe the main variability within a dataset and thus represent the main movement patterns. However, while subtle changes in gait pattern (for instance, due to different footwear) may not change main movement patterns, they may affect movements represented by higher principal components. This study was designed to test two hypotheses: (1) speed and gender differences can be observed in the first principal components, and (2) small interventions such as changing footwear change the gait characteristics of higher principal components. Kinematic changes due to different running conditions (speed - 3.1m/s and 4.9 m/s, gender, and footwear - control shoe and adidas MicroBounce shoe) were investigated by applying PCA and support vector machine (SVM) to a full-body reflective marker setup. Differences in speed changed the basic movement pattern, as was reflected by a change in the time-dependent coefficient derived from the first principal. Gender was differentiated by using the time-dependent coefficient derived from intermediate principal components. (Intermediate principal components are characterized by limb rotations of the thigh and shank.) Different shoe conditions were identified in higher principal components. This study showed that different interventions can be analyzed using a full-body kinematic approach. Within the well-defined vector space spanned by the data of all subjects, higher principal components should also be considered because these components show the differences that result from small interventions such as footwear changes. PMID- 22304786 TI - Declining Guillain-Barre syndrome after campylobacteriosis control, New Zealand, 1988-2010. AB - Infection with Campylobacter spp. commonly precedes Guillain-Barre syndrome (GBS). We therefore hypothesized that GBS incidence may have followed a marked rise and then decline in campylobacteriosis rates in New Zealand. We reviewed records for 1988-2010: hospitalization records for GBS case-patients and campylobacteriosis case-patients plus notifications of campylobacteriosis. We identified 2,056 first hospitalizations for GBS, an average rate of 2.32 hospitalizations/100,000 population/year. Annual rates of hospitalization for GBS were significantly correlated with rates of notifications of campylobacteriosis. For patients hospitalized for campylobacteriosis, risk of being hospitalized for GBS during the next month was greatly increased. Three years after successful interventions to lower Campylobacter spp. contamination of fresh poultry meat, notifications of campylobacteriosis had declined by 52% and hospitalizations for GBS by 13%. Therefore, regulatory measures to prevent foodborne campylobacteriosis probably have an additional health and economic benefit of preventing GBS. PMID- 22304785 TI - Critical care management of severe traumatic brain injury in adults. AB - Traumatic brain injury (TBI) is a major medical and socio-economic problem, and is the leading cause of death in children and young adults. The critical care management of severe TBI is largely derived from the "Guidelines for the Management of Severe Traumatic Brain Injury" that have been published by the Brain Trauma Foundation. The main objectives are prevention and treatment of intracranial hypertension and secondary brain insults, preservation of cerebral perfusion pressure (CPP), and optimization of cerebral oxygenation. In this review, the critical care management of severe TBI will be discussed with focus on monitoring, avoidance and minimization of secondary brain insults, and optimization of cerebral oxygenation and CPP. PMID- 22304787 TI - Prohibitin in squamous cell carcinoma of the lung: its expression and possible clinical significance. AB - rohibitin is localized to mitochondria where it might have a role in the maintenance of mitochondrial function and protection against senescence. In this study, we show that prohibitin is up-regulated in lung squamous cell carcinoma tissues compared with adjacent normal tissues using agarose 2-dimensional differential gel electrophoresis and immunoblotting. Prohibitin expression was further evaluated by immunohistochemistry. We statistically analyzed the association of prohibitin expression with clinicopathologic indicators in 78 patients with lung squamous cell carcinoma. Our data suggested that prohibitin expression was positively correlated with the International Union Against Cancer (UICC) classification of tumor grade (P < .001), pathologic stage (P < .001), tumor size (P = .01), and lymph node metastasis (P = .004). Furthermore, we found that prohibitin expression was an independent prognostic indicator (P = .037) for overall survival of patients with lung squamous cell carcinoma by multivariate analysis using the Cox regression method. These findings may encourage further studies investigating prohibitin function in lung squamous cell carcinoma. PMID- 22304788 TI - Activated leukocyte cell adhesion molecule is expressed in neuroepithelial neoplasms and decreases with tumor malignancy, matrix metalloproteinase 2 expression, and absence of IDH1R132H mutation. AB - Diffuse growth of gliomas is based on enhanced cell migration and remodeling of the extracellular matrix. Up-regulation of matrix metalloproteinases in gliomas is associated with a poor prognosis. The activated leukocyte adhesion molecule is considered to be indispensable for conversion of matrix metalloproteinase 2 into its active form. We therefore investigated the expression of activated leukocyte adhesion molecule in 9 malignant glial cell lines, 105 normal/reactive human brain specimens, 248 astrocytomas/glioblastomas, 98 ependymomas, 35 oligodendrogliomas, 10 neurocytomas, 10 primitive neuroectodermal tumors (PNET), and 36 medulloblastomas by immunohistochemistry and in selected cases by reverse transcriptase polymerase chain reaction. Correlation between activated leukocyte adhesion molecule expression and tumor grades and entities, proliferation activity, matrix metalloproteinase 2 expression, prognostic isocitrate dehydrogenase (IDH)1 mutation (R132H) status, O-6-methylguanine DNA methyltransferase (MGMT) promoter status, or association with patient survival were analyzed. All oligodendrogliomas were strongly activated leukocyte adhesion molecule positive. Numbers of activated leukocyte adhesion molecule positive tumors were higher in glioblastomas (93%) than in diffuse astrocytomas (83%), but mean expression intensity was significantly reduced. Anaplastic ependymomas (68%) exhibited reduced numbers of activated leukocyte adhesion molecule-positive tumors and staining intensity compared with lower-grade ependymomas (85%). Activated leukocyte adhesion molecule expression in gliomas was independent of proliferative activity, MGMT status, patient survival, and age, whereas gliomas with IDH1 (R132H) mutation had significantly higher activated leukocyte adhesion molecule levels than their wild-type counterparts. Matrix metalloproteinase 2 negative glioblastomas exhibited significantly reduced activated leukocyte adhesion molecule expression levels compared with astrocytomas. In summary, our findings indicate that activated leukocyte adhesion molecule expression levels in gliomas are probably linked to other mechanisms than its supposed role as regulator of matrix metalloproteinase 2. PMID- 22304789 TI - Hepatic angiosarcoma mimicking sinusoidal obstruction syndrome/venoocclusive disease: a pathologic-radiologic correlation. AB - We present a case of a 63-year-old man with liver dysfunction and biopsy findings of venoocclusive disease (VOD) who, at autopsy, was discovered to have multifocal hepatic angiosarcoma. After double lung transplantation, he initially presented with signs of liver failure and portal hypertension resulting in recurrent high volume ascites. Clinically, VOD was considered, and tacrolimus was discontinued, due to its known association with VOD. This, however, did not result in clinical improvement, and computed tomography eventually revealed the development of multiple low-attenuating hepatic lesions over the course of several months. Biopsies of the masses and background liver demonstrated changes most consistent with VOD, characterized by sinusoidal congestion affecting the centrilobular areas with associated hepatocyte atrophy and dropout. A reticulin stain highlighted deposition of reticulin fibers within the sinusoids and central veins. Scattered sinusoidal atypical cells were identified; however, a definitive diagnosis of malignancy was not possible. He eventually passed away because of complications of liver disease. At autopsy, there were multiple firm, red-brown masses identified throughout both hepatic lobes. Upon histologic review, the masses were shown to be angiosarcoma. Away from the tumor, the liver also demonstrated features of VOD. It is likely that the histologic appearance of VOD in the background liver probably represents secondary changes due to injury to the hepatic sinusoids by the primary malignancy. We conclude that it is necessary to consider the possibility of unsampled vascular malignancy when hepatic masses are identified on imaging and histology is consistent with VOD. PMID- 22304791 TI - Applicability of an adapted medication appropriateness index for detection of drug-related problems in geriatric inpatients. AB - BACKGROUND: High drug consumption by older patients and the presence of many drug related problems require careful assessment of drug therapy, for which a structured approach is recommended. OBJECTIVE: The purpose of our study was to evaluate the applicability of an adapted version of the Medication Appropriateness Index (MAI) in 50 geriatric inpatients at the time of admission. METHODS: We reviewed, for 432 prescribed drugs, indication, right choice, dosage, directions, drug-disease interactions, drug-drug interactions, and duration of therapy. In addition, adverse drug reactions were evaluated, resulting in 8 questions per drug. MAI scores were attributed independently by a geriatrician and by a clinical pharmacist, and differences between them were assessed. Furthermore, the relationship between MAI score and drug-related hospital admission was explored. RESULTS: Mean summed MAI scores of 13.7 according to the geriatrician and 13.6 according to the pharmacist were obtained. The highest scores were found for drugs for the central nervous and the urinary tract system; the highest scores per question were detected for right choice, adverse drug reactions, and drug-drug interactions. A good agreement between the scores of the geriatrician and the pharmacist was found: intraclass correlation coefficient was 0.91 and overall kappa value was 0.71. A significantly higher MAI score was found for drug-related hospital admissions (P = 0.04 for the geriatrician and P = 0.03 for the pharmacist). CONCLUSIONS: This adapted MAI score seems useful for detection of drug-related problems in geriatric inpatients and reliable with a low inter-rater variability and positive correlation between high score and drug related hospital admission. We consider further application of the adapted MAI for teaching and training of clinical pharmacists, and as a systematic approach for detection of drug-related problems by the clinical pharmacists in our hospital. PMID- 22304790 TI - Occupational exposures among nurses and risk of spontaneous abortion. AB - OBJECTIVE: We investigated self-reported occupational exposure to antineoplastic drugs, anesthetic gases, antiviral drugs, sterilizing agents (disinfectants), and X-rays and the risk of spontaneous abortion in US nurses. STUDY DESIGN: Pregnancy outcome and occupational exposures were collected retrospectively from 8461 participants of the Nurses' Health Study II. Of these, 7482 were eligible for analysis using logistic regression. RESULTS: Participants reported 6707 live births, and 775 (10%) spontaneous abortions (<20 weeks). After adjusting for age, parity, shift work, and hours worked, antineoplastic drug exposure was associated with a 2-fold increased risk of spontaneous abortion, particularly with early spontaneous abortion before the 12th week, and 3.5-fold increased risk among nulliparous women. Exposure to sterilizing agents was associated with a 2-fold increased risk of late spontaneous abortion (12-20 weeks), but not with early spontaneous abortion. CONCLUSION: This study suggests that certain occupational exposures common to nurses are related to risks of spontaneous abortion. PMID- 22304792 TI - Molecular mechanisms of RNA-triggered gene silencing machineries. AB - Gene silencing by RNA triggers is an ancient, evolutionarily conserved, and widespread phenomenon. This process, known as RNA interference (RNAi), occurs when double-stranded RNA helices induce cleavage of their complementary mRNAs. Because these RNA molecules can be introduced exogenously as small interfering RNAs (siRNAs), RNAi has become an everyday experimental tool in laboratory research. In addition, the number of RNA-based therapeutics that are currently in clinical trials for a variety of human diseases demonstrate the therapeutic potential of RNAi. In this Account, we focus on our current understanding of the structure and function of various classes of RNAi triggers and how this knowledge has contributed to our understanding of the biogenesis and catalytic functions of siRNA and microRNA in mammalian cells. Mechanistic studies to understand the structure and function of small RNAs that induce RNAi have illuminated broad functions of the ancient RNAi machinery in animals and plants. In addition, such studies have provided insight to identify endogenous physiological gene silencing RNA triggers that engage functional machineries similar to siRNAs. Several endogenous small RNA species have been identified: small noncoding RNAs (microRNAs), piwi-interacting RNAs (piRNAs), and endogenous siRNAs (endo-siRNAs). microRNAs are the most widespread class of small RNAs in mammalian cells. Despite their importance in biology and medicine, the molecular and cellular mechanisms of microRNA biogenesis and function are not fully understood. We provide an overview of the current understanding of how these molecules are synthesized within cells and how they act on gene targets. Interesting questions remain both for understanding the effects of modifications and editing on microRNAs and the interactions between microRNAs and other cellular RNAs such as long noncoding RNAs. PMID- 22304793 TI - Renal safety of intensive cholesterol-lowering treatment with rosuvastatin: a retrospective analysis of renal adverse events among 40,600 participants in the rosuvastatin clinical development program. AB - OBJECTIVE: Intensive lowering of low-density lipoprotein cholesterol (LDL-C) with statins reduces cardiovascular risk but can cause liver-, muscle-, and possibly renal-related adverse events (AEs). We assessed the effects of rosuvastatin on the risk of developing renal impairment or renal failure among participants in the rosuvastatin clinical development program. METHODS: The analysis was based on AE data reported by investigators from 36 studies that included 40,600 participants who did not have advanced, pre-existing renal disease. Rates of renal AEs were determined based on time to first occurrence of renal impairment or renal failure. RESULTS: Renal impairment or renal failure was reported in 536 study participants during 72,488 patient-years of follow-up. Renal event rates were higher in patients with history of heart failure (n = 5011), hypertension (n = 21,864), diabetes (n = 5165), or estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) (n = 9507) at baseline but did not differ with rosuvastatin compared with placebo or with rosuvastatin 40 mg compared with rosuvastatin 10mg. Relative risk (RR) estimates obtained from pooled analysis of placebo-controlled trials were RR: 1.03 (95% CI: 0.86-1.23, p = 0.777) for any reported renal impairment or renal failure event, RR: 1.02 (95% CI: 0.76-1.37, p = 0.894) for serious renal AEs, and RR: 0.70 (95% CI: 0.36-1.35, p = 0.282) for renal AEs leading to death. CONCLUSION: These findings suggest that intensive LDL-C lowering treatment with rosuvastatin does not affect the risk of developing renal insufficiency or renal failure in patients who do not have advanced, pre-existing renal disease. PMID- 22304794 TI - Psychological stress, immune response, and atherosclerosis. AB - It is well known that psychological stress is associated with increased atherosclerosis. This response is mainly mediated by altered immune reactions due to either activation or depression of the hypothalamic-pituitary-adrenal (HPA) regulatory feed back mechanisms that influence both the vascular endothelium function and the recruitment of circulating monocytes and their conversion to foam cells. Although the detailed mechanisms behind these processes are not well understood, it has been assumed that expression of pro- and anti-inflammatory cytokines by stress hormones, such as catecholamines and corticosteroids, maybe involved. In this review, we focus on evidences that various immunological factors are transformed under prolonged psychological stress by causing vascular low-grade inflammation. A better understanding of the bidirectional communication between the neuroendocrine and immune systems may contribute to new treatment strategies. PMID- 22304795 TI - Health utility after emergency medical admission: a cross-sectional survey. AB - OBJECTIVES: Health utility combines health related quality of life and mortality to produce a generic outcome measure reflecting both morbidity and mortality. It has not been widely used as an outcome measure in evaluations of emergency care and little is known about the feasibility of measurement, typical values obtained or baseline factors that predict health utility. We aimed to measure health utility after emergency medical admission, to compare health utility to age, gender and regional population norms, and identify independent predictors of health utility. METHODS: We selected 5760 patients across three hospitals who were admitted to hospital by ambulance as a medical emergency. The EQ-5D questionnaire was mailed to all who were still alive 30 days after admission. Health utility was estimated by applying tariff values to the EQ-5D responses or imputing a value of zero for those who had died. Multivariable analysis was used to identify independent predictors of health utility at 30 days. RESULTS: Responses were received from 2488 (47.7%) patients, while 541 (9.4%) had died. Most respondents reported some or severe problems with each aspect of health. Mean health utility was 0.49 (standard deviation 0.35) in survivors and 0.45 (0.36) including non-survivors. Some 75% had health utility below their expected value (mean loss 0.32, 95% confidence interval 0.31 to 0.33) and 11% had health utility below zero (worse than death). On multivariable modelling, reduced health utility was associated with increased age and lower GCS, varied according to ICD10 code and was lower among females, patients with recent hospital admission, steroid therapy, or history of chronic respiratory disease, malignancy, diabetes or epilepsy. CONCLUSIONS: Health utility can be measured after emergency medical admission, although responder bias may be significant. Health utility after emergency medical admission is poor compared to population norms. We have identified independent predictors or health utility that need to be measured and taken into account in non-randomized evaluations of emergency care. PMID- 22304796 TI - Orientation-independent charge transport in single spherulites from solution processed organic semiconductors. AB - Due to the rapidity of morphological development during deposition, solution processed organic semiconductor thin films exist in semicrystalline or polycrystalline states, incorporating a high degree of local variations in molecular orientation compared to their single-crystal counterparts. Spherulites, a common crystalline superstructure found in these systems, for example, incorporate a large distribution of molecular orientations about the radial axis to maintain their space-filling growth habit. Here, we aim to determine how this distribution of molecular orientations influences charge transport by fabricating arrays of devices on single spherulites. Given that the orientation distribution that is present about the radial axis mandates the presence of low-angle grain boundaries within single spherulites, we find intraspherulitic charge transport to be independent of the general direction of pi-stacking; organic field-effect transistors exhibit comparable mobilities regardless of how their channels are oriented with respect to the general pi-stacking direction. PMID- 22304797 TI - Axillary node metastasis from differentiated thyroid carcinoma with Hurthle and signet ring cell differentiation. A case of disseminated thyroid cancer with peculiar histologic findings. AB - BACKGROUND: Differentiated thyroid cancer is usually associated with an excellent prognosis and indolent course. Distant metastases are rare events at the onset of thyroid cancer. Among these presentations, metastasis to the axillary lymph nodes is even more unusual: only few cases were previously reported in the literature; there has been no report of axillary lymph node metastasis from follicular thyroid carcinoma. Axillary lymph node metastasis generally arises in the context of disseminated disease and carries an ominous prognosis. CASE PRESENTATION: Here we present a case of axillary lymph node metastasis in the context of disseminated differentiated thyroid cancer. The patient underwent near total thyroidectomy and neck and axillary lymph node dissection. A histopathological diagnosis of poorly differentiated follicular carcinoma with "signet ring cells" and Hurthle cell features was established. The patient received radioactive iodine therapy and TSH suppression therapy. Subsequently his serum thyroglobulin level decreased to 44.000 ng/ml from over 100.000 ng/ml. DISCUSSION AND CONCLUSION: Currently there are only few reported cases of axillary node metastases from thyroid cancer, and to our knowledge, this is the first report on axillary lymph node metastasis from follicular thyroid carcinoma. "Signet ring cell" is a morphologic feature shared by both benign and, more rarely, malignant follicular thyroid neoplasm, and it generally correlates with an arrest in folliculogenesis. Our case is one of the rare "signet ring cells" carcinomas so far described. PMID- 22304798 TI - Preventive use of noninvasive ventilation after planned extubation. PMID- 22304799 TI - A peek at PEEP in patients with AIDS. PMID- 22304800 TI - High-frequency chest wall compressions: good for the patient? Good for the clinician? PMID- 22304801 TI - Obstructive sleep apnea and prolonged mechanical ventilation. PMID- 22304802 TI - Accuracy and reliability of extubation decisions by intensivists. PMID- 22304803 TI - Critical illness related pneumonia rather than Ventilator-Associated Pneumonia (VAP). PMID- 22304804 TI - Additional experimental evidence that statins protect against acute lung injury. PMID- 22304805 TI - Pediatric asthma management. PMID- 22304806 TI - Synthesis and anticonvulsant activity of 1-(2-(8-(benzyloxy)quinolin-2-yl)-1 butyrylcyclopropyl)-3-substituted urea derivatives. AB - In the present study on the development of new anticonvulsants, 16 new1-(2-(8 (benzyloxy)quinolin-2-yl)-1-butyrylcyclopropyl)-3-substituted urea derivatives were synthesized and tested for anticonvulsant activity using the maximal electroshock seizure, subcutaneous pentylenetetrazole screens, which are the most widely employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined by applying the rotorod test. Three compounds 7a, 7e, and 7m showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 7e showed the maximal electroshock seizure-induced seizures with ED(50) value of 14.3 mg/kg and TD(50) value of 434 mg/kg after intraperitoneal injection to mice, which provided compound 7e with a protective index (TD(50) /ED(50) ) of 30.3 in the maximal electroshock seizure test. PMID- 22304807 TI - Rickettsia felis infection in febrile patients, western Kenya, 2007-2010. AB - To determine previous exposure and incidence of rickettsial infections in western Kenya during 2007-2010, we conducted hospital-based surveillance. Antibodies against rickettsiae were detected in 57.4% of previously collected serum samples. In a 2008-2010 prospective study, Rickettsia felis DNA was 2.2* more likely to be detected in febrile than in afebrile persons. PMID- 22304808 TI - Prehospital trauma care reduces mortality. Ten-year results from a time-cohort and trauma audit study in Iraq. AB - BACKGROUND: Blunt implementation of Western trauma system models is not feasible in low-resource communities with long prehospital transit times. The aims of the study were to evaluate to which extent a low-cost prehospital trauma system reduces trauma deaths where prehospital transit times are long, and to identify specific life support interventions that contributed to survival. METHODS: In the study period from 1997 to 2006, 2,788 patients injured by land mines, war, and traffic accidents were managed by a chain-of-survival trauma system where non graduate paramedics were the key care providers. The study was conducted with a time-period cohort design. RESULTS: 37% of the study patients had serious injuries with Injury Severity Score >= 9. The mean prehospital transport time was 2.5 hours (95% CI 1.9 - 3.2). During the ten-year study period trauma mortality was reduced from 17% (95% CI 15 -19) to 4% (95% CI 3.5 - 5), survival especially improving in major trauma victims. In most patients with airway problems, in chest injured, and in patients with external hemorrhage, simple life support measures were sufficient to improve physiological severity indicators. CONCLUSION: In case of long prehospital transit times simple life support measures by paramedics and lay first responders reduce trauma mortality in major injuries. Delegating life-saving skills to paramedics and lay people is a key factor for efficient prehospital trauma systems in low-resource communities. PMID- 22304809 TI - Pathogenesis of avian bornavirus in experimentally infected cockatiels. AB - Avian bornavirus (ABV) is the presumed causative agent of proventricular dilatation disease (PDD), a major fatal disease in psittacines. However, the influencing factors and pathogenesis of PDD are not known and natural ABV infection exhibits remarkable variability. We investigated the course of infection in 18 cockatiels that were intracerebrally and intravenously inoculated with ABV. A persistent ABV infection developed in all 18 cockatiels, but, as in natural infection, clinical disease patterns varied. Over 33 weeks, we simultaneously studied seroconversion, presence of viral RNA and antigens, infectious virus, histopathologic alterations, and clinical signs of infection in the ABV-infected birds. Our study results further confirm the etiologic role of ABV in the development of PDD, and they provide basis for further investigations of the pathogenetic mechanisms and disease-inducing factors for the development of PDD. PMID- 22304810 TI - A simple method using on-line continuous leaching and ion exchange chromatography coupled to inductively coupled plasma mass spectrometry for the speciation analysis of bio-accessible arsenic in rice. AB - A simple method for the speciation analysis of bio-accessible arsenic (As) in rice was developed using a continuous on-line leaching method to release the bio accessible fraction. The continuous on-line leaching method has several advantages over commonly used batch methods including quicker and easier sample preparation, reduced risk of contamination and access to real time leaching data. The bio-accessibility of As in the samples was monitored using inductively coupled plasma mass spectrometry (ICP-MS). Results from a certified reference material as well as cooked and uncooked white rice showed that the majority of As was leached by saliva. Results obtained using the continuous on-line leaching method were comparable to those obtained using a batch method. Speciation analysis of the saliva leachate was performed using ion exchange chromatography coupled to ICP-MS. The four most toxic forms of As (As(III), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and As(V)) were clearly separated within 5 min in a single chromatographic run. Over 92% of bio-accessible As in the certified reference material and uncooked white rice sample was in the form of DMA and As(V), whereas it was present as DMA and As(III) in the cooked white rice. PMID- 22304811 TI - Photopolymerization and photostructuring of molecularly imprinted polymers for sensor applications--a review. AB - Biosensors are already well established in modern analytical chemistry, and have become important tools for clinical diagnostics, environmental analysis, production monitoring, drug detection or screening. They are based on the specific molecular recognition of a target molecule by a biological receptor such as an antibody or an enzyme. Synthetic biomimetic receptors like molecularly imprinted polymers (MIPs) have been shown to be a potential alternative to biomolecules as recognition element for biosensing. Produced by a templating process at the molecular level, MIPs are capable of recognizing and binding target molecules with similar specificity and selectivity to their natural analogues. One of the main challenges in MIP sensor development is the miniaturization of MIP structures and their interfacing with the transducer or with a microchip. Photostructuring appears thereby as one of the most suitable methods for patterning MIPs at the micro and nano scale, directly on the transducer surface. In the present review, a general overview on MIPs in biosensing applications is given, and the photopolymerization and photopatterning of MIPs are particularly described. PMID- 22304812 TI - The use of electrothermal vaporizer coupled to the inductively coupled plasma mass spectrometry for the determination of arsenic, selenium and transition metals in biological samples treated with formic acid. AB - A fast method for the determination of As, Co, Cu, Fe, Mn, Ni, Se and V in biological samples by ETV-ICP-MS, after a simple sample treatment with formic acid, is proposed. Approximately 75 mg of each sample is mixed with 5 mL of formic acid, kept at 90 degrees C for 1 h and then diluted with nitric acid aqueous solution to a 5% (v/v) formic acid and 1% (v/v) nitric acid final concentrations. A palladium solution was used as a chemical modifier. The instrumental conditions, such as carrier gas flow rate, RF power, pyrolysis and vaporization temperatures and argon internal flow rate during vaporization were optimized. The formic acid causes a slight decrease of the analytes signal intensities, but does not increase the signal of the mainly polyatomic ions ((14)N(35)Cl(+), (14)N(12)C(+), (40)Ar(12)C(+), (13)C(37)Cl(+), (40)Ar(36)Ar(+), (40)Ar(35)Cl(+), (35)Cl(16)O(+), (40)Ar(18)O(+)) that affect the analytes signals. The effect of charge transfer reactions, that could increase the ionization efficiency of some elements with high ionization potentials was not observed due to the elimination of most of the organic compounds during the pyrolysis step. External calibration with aqueous standard solutions containing 5% (v/v) formic acid allows the simultaneous determination of all analytes with high accuracy. The detection limits in the samples were between 0.01 (Co) and 850 MUg kg(-1) (Fe and Se) and the precision expressed by the relative standard deviations (RSD) were between 0.1% (Mn) and 10% (Ni). Accuracy was validated by the analysis of four certified reference biological materials of animal tissues (lobster hepatopancreas, dogfish muscle, oyster tissue and bovine liver). The recommended procedure avoids plasma instability, carbon deposit on the cones and does not require sample digestion. PMID- 22304813 TI - Online characterization of regulated and unregulated gaseous and particulate exhaust emissions from two-stroke mopeds: a chemometric approach. AB - Two-stroke mopeds are a popular and convenient mean of transport in particular in the highly populated cities. These vehicles can emit potentially toxic gaseous and aerosol pollutants due to their engine technology. The legislative measurements of moped emissions are based on offline methods; however, the online characterization of gas and particulate phases offers great possibilities to understand aerosol formation mechanism and to adapt future emission standards. The purpose of this work was to study the emission behavior of two mopeds complying with different European emission standards (EURO-1 and EURO-2). A sophisticated set of online analyzers was applied to simultaneously monitor the gas phase and particulate phase of exhaust on a real time basis. The gaseous emission was analyzed with a high resolution Fourier transform infrared spectrometer (FTIR; nitrogen species) and a resonance-enhanced multiphoton ionization time-of-flight mass spectrometer (REMPI-ToF-MS; polycyclic aromatic hydrocarbons: PAH), whereas the particulate phase was chemically characterized by a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS; organic, nitrate and chloride aerosol) and a multiangle absorption photometer (MAAP; black carbon). The physical characterization of the aerosol was carried out with a condensation particle counter (CPC; particle number concentration) and a fast mobility particle sizer (FMPS; size distribution in real time). In order to extract underlying correlation between gas and solid emissions, principal component analysis was applied to the comprehensive online dataset. Multivariate analysis highlighted the considerable effect of the exhaust temperature on the particles and heavy PAH emissions. The results showed that the after-treatment used to comply with the latest EURO-2 emission standard may be responsible for the production of more potentially harmful particles compared to the EURO-1 moped emissions. PMID- 22304814 TI - Tracing the origin of extra virgin olive oils by infrared spectroscopy and chemometrics: a case study. AB - In this paper, the potential of coupling mid- and near-infrared spectroscopic fingerprinting techniques and chemometric classification methods for the traceability of extra virgin olive oil samples from the PDO Sabina was investigated. To this purpose, two different pattern recognition algorithm representative of the discriminant (PLS-DA) and modeling (SIMCA) approach to classification were employed. Results obtained after processing the spectroscopic data by PLS-DA evidenced a rather high classification accuracy, NIR providing better predictions than MIR (as evaluated both in cross-validation and on an external test set). SIMCA confirmed these results and showed how the category models for the class Sabina can be rather sensitive and highly specific. Lastly, as samples from two harvesting years (2009 and 2010) were investigated, it was possible to evidence that the different production year can have a relevant effect on the spectroscopic fingerprint. Notwithstanding this, it was still possible to build models that are transferable from one year to another with good accuracy. PMID- 22304815 TI - Cross-column retention prediction in reversed-phase high-performance liquid chromatography by artificial neural network modelling. AB - Linear solvation energy relationships (LSERs) are commonly applied to model the effect of solute structure on the retention of analytes in reversed-phase high performance liquid chromatography (RP-HPLC). Standard LSER approaches can be used, in principle, to predict RP-HPLC behaviour of unknown analytes under fixed separation condition. However, as solute structure is the only source of variability described by the model, a LSER established for a given column/eluent pair cannot be transferred to external separation conditions. In the present investigation, we attempt cross-column prediction by combining in the same model usual LSER molecular descriptors with observed retentions of selected solutes within the calibration set, adopted to represent the stationary phase features. A multi-layer artificial neural network (ANN) is used as regression tool to model the combined effect of solute structure and column on retention. This model is generated and validated using literature retention data of 34 solutes collected on 15 different RP-HPLC columns at a fixed eluent composition (acetonitrile-water 30:70, v/v). The calibration set is designed by selecting 25 solutes and 11 columns able to represent the variability of the chemical structure of the investigated compounds and dissimilarity of the stationary phases of the data set, respectively. The final predictive performance of the optimised ANN model is tested on the four columns excluded from calibration. Retention of the 25 solutes used to train the network and that of the nine unknown molecules on the external stationary phases is comparably well predicted. PMID- 22304816 TI - A superoxide anion biosensor based on direct electron transfer of superoxide dismutase on sodium alginate sol-gel film and its application to monitoring of living cells. AB - The direct electron transfer of superoxide dismutase (SOD) was greatly facilitated by sodium alginate (SA) sol-gel film with the formal potential of 0.14 V, which was just located between O(2)(*-)/O(2) and O(2)(*-)/H(2)O(2). The preparation of the SOD/SA modified electrode was simple without any mediators or promoters. Based on bimolecular recognition for specific reactivity of SOD/SA toward O(2)(*-), the SOD modified electrode was utilized to measure O(2)(*-) with good analytical performance, such as low applied potential (0 V), high selectivity (no obvious interference), wide linear range (0.44-229.88 MUM) and low detection limit (0.23 MUM) in pH 7.0 phosphate buffer solution. Furthermore, it could be successfully exploited for the determination of O(2)(*-) released from living cells directly adhered on the modified electrode surface. Thus, the proposed O(2)(*-) biosensor, combining with the properties of SA sol-gel film, provided a novel approach for protein immobilization, direct electron transfer study of the immobilized protein and real-time determination of O(2)(*-) released from living cells. PMID- 22304817 TI - Development of a multiplex UPLC-MRM MS method for quantification of human membrane transport proteins OATP1B1, OATP1B3 and OATP2B1 in in vitro systems and tissues. AB - OATP1B1, OATP1B3 and OATP2B1 are important members of the organic anion transporting polypeptides (OATP) family and are implicated in the hepatic disposition of endobiotics and xenobiotics. Quantitating the expression levels of human OATP1B1, OATP1B3 and OATP2B1 in in vitro systems and tissue samples could significantly improve attempts to scale up in vitro data and result in more effective in vitro-in vivo correlation of transporter-mediated effects on drug disposition, such as hepatic clearance. In the present study, a quantification method was developed, characterized, and implemented for simultaneous determination of human OATP1B1, OATP1B3 and OATP2B1 in HEK cells transfected with OATP-expressing plasmid vectors (SLCO1B1, SLCO1B3, and SLCO2B1, respectively), human hepatocytes, human brain capillary endothelial cells, and humanized mouse liver tissue using UPLC-MRM MS. Purified membrane protein standards prepared and characterized as previously reported (Protein Expr. Purif. 2008, 57, 163-71) were first used as standards for absolute quantification of the expression levels of the three human OATP membrane proteins. The specificity of the optimized MRM transitions were characterized by analyzing the tryptic digests of the membrane protein fraction of wild type HEK cells and control mouse liver tissue using the herein reported UPLC-MRM MS method. The linearity of the calibration curve spanned from 0.2 MUg mL(-1) (0.040 MUg mg(-1)) to 20 MUg mL(-1) (4.0 MUg mg(-1)), with accuracy (% RE) within 15% at all concentrations examined for all three OATPs of interest in this study. The intra- and inter-day assay accuracy (% RE) and coefficient of variations (% CV) of triplicates are all within 15% for all levels of quality control samples prepared by mixing the membrane fraction of control mouse liver tissue with the required amount of purified human OATP1B1, OATP1B3 and OATP2B1. PMID- 22304818 TI - Natural dissolved organic matter affects electrospray ionization during analysis of emerging contaminants by mass spectrometry. AB - Dissolved organic matter (DOM), present in many forms in water, can interfere with analysis of organic contaminants by atmospheric pressure ionization-mass spectrometry. A quantitative analysis of this interference, or matrix effect, on organic contaminant target analyte measurements was carried out using un fractionated and fractionated dissolved natural organic matter from the Suwannee River, GA (SROM), a standard reference material, that was directly infused into the tandem mass spectrometer during multiple reaction monitoring (MRM) of a suite of endocrine disrupting compounds-pharmaceuticals and personal care products (EDC/PPCPs). Most target analytes suffered signal suppression in the presence of both fractionated and un-fractionated SROM, however greater interferences were measured with fractionated relative to bulk SROM. This finding is consistent with the view of organic matter as a supramolecular association of low molecular mass components having separate charged and structural features revealed only after dissociation. PMID- 22304819 TI - Endogenous and synthetic steroids in bovine urine--preparation of in-house reference material, stability studies and results of a proficiency test. AB - Within the framework of the German National Residue Control Plan a specific number of samples of animal origin have to be analysed for natural and synthetic steroids each year. As a measure of external quality control of the methods applied in routine analysis a proficiency test was carried out. To this end, in house reference material containing incurred residues of 17alpha- and 17beta nortestosterone and 17alpha- and 17beta-estradiol as well as fortified residues of 17alpha-methyltestosterone and 17alpha-trenbolone in bovine urine were produced. Before sending the proficiency test material to the participants, the homogeneity of all samples was tested and confirmed. Furthermore extensive short- and long-term stability studies were carried out. The statistical evaluation of the proficiency test was performed by applying robust statistics as described in standard DIN 38402. Based on the target value and standard deviation z-scores were calculated as standardised measure of the laboratory performance. The evaluation of the proficiency test showed that nine laboratories submitted quantitative results within the tolerance limits for all analytes. Taking into account the individual decision limits, there were no false negative results. In overall evaluation, 11 of 12 laboratories participated successfully. PMID- 22304820 TI - Comparative analysis of smokeless gunpowders by Fourier transform infrared and Raman spectroscopy. AB - Fourier Transform Infrared (FTIR) and Raman spectroscopic techniques were used to perform a comparative study of the spectral profiles of single-base, double-base and triple-base smokeless gunpowders. Preliminary results based on visual comparison of the spectra point out that spectra obtained by both vibrational techniques were useful for a rapid identification of gunpowders containing dinitrotoluene as one of the major components and triple-base gunpowders. Additionally, the Raman spectra of gunpowders with diphenylamine in its primary composition showed a characteristic band, assigned to 2-nitro-diphenylamine, allowing the identification of this type of gunpowders. Further differentiation among the spectra of different types of smokeless gunpowders obtained by both vibrational spectroscopic techniques was investigated by discriminant analysis. Different analyses were applied to spectral data considering the different composition of gunpowders. The presence or absence of different compounds (such as dinitrotoluene, diphenylamine or dibutyl phthalate) or the type of gunpowder according to the number of active components (single-base or double-base gunpowder) has been taken into account. FTIR and Raman spectroscopy in combination with discriminant analyses were successful tools of forensic interest for the classification of gunpowders and the possible identification of unknown samples of gunpowders. PMID- 22304821 TI - Multi-way partial least-squares and residual bi-linearization for the direct determination of monohydroxy-polycyclic aromatic hydrocarbons on octadecyl membranes via room-temperature fluorescence excitation emission matrices. AB - Multi-way partial least-squares (N-PLS) is combined to the residual bi linearization procedure (RBL) for the direct analysis of metabolites of polycyclic aromatic hydrocarbons in urine samples. Metabolite analysis is carried out via a two-step experimental procedure based on solid-phase extraction and room temperature fluorescence spectroscopy. Excitation-emission matrices are recorded from octadecyl (C18) membranes that serve as solid substrates for sample extraction and spectroscopic measurements. Excellent metabolite recoveries were obtained in all cases, which varied from 96.2+/-1.35% (9-hydroxyphenanthrene) to 99.7+/-0.49% (3-hydroxybenzo[a]pyrene). Background correction of extraction membranes is carried out with a new alternating least-squares (ALS) procedure adapted to second order data. The performance of N-PLS/RBL is compared to the well-established multivariate curve resolution-alternating least-squares (MCR ALS) algorithm. Both algorithms provided similar analytical figures of merit, including their ability to handle unknown interference in urine samples. With only 10 mL of sample, the limits of detection varied between 0.06-0.08 ng mL(-1) (1-hydroxypyrene) and 0.016-0.018 ng mL(-1) (2-hydroxyfluorene). When compared to previously reported univariate calibration data, the limits of detection via N PLS/RBL and MCR-ALS are approximately one order of magnitude higher. This was somehow expected due to the effect of unexpected components in multivariate figures of merit, i.e. a more realistic approach to the analysis of metabolites in human urine samples. PMID- 22304822 TI - Investigation of gamma radiation effect on the anion exchange resin Amberlite IRA 400 in hydroxide form by Fourier transformed infrared and 13C nuclear magnetic resonance spectroscopies. AB - Radiation-induced decomposition of the anion exchange resin Amberlite IRA-400 in hydroxide form by gamma radiolysis has been studied under different irradiation doses and irradiation atmospheres. In this work, we focused on the degradation of the solid part of the resin by Fourier transformed infrared (FTIR) and (13)C nuclear magnetic resonance (NMR) spectroscopies associated with chemometric treatments. FTIR and (13)C NMR techniques showed that only -CH(2)N(+)(CH(3))(3) groups were detached from the resin whereas the polystyrene divinylbenzene backbone remains intact. The quaternary ammonium groups were replaced by amine or carbonyl groups according to the irradiation atmosphere (with or without water or oxygen). Principal components analysis (PCA) was used to classify the degraded resins according to their irradiation conditions by separating the effect of the dose or the environment. The PCA loadings have shown spectral regions which discriminate the irradiated resins whereas SIMPLe-to-use Interactive Self modeling Mixture Analysis (SIMPLISMA) allows to identify families of component characterizing the chemical structure of resins and estimate their relative contributions according to the irradiation atmospheres. PMID- 22304823 TI - A fluorescent chemosensor for Hg2+ based on naphthalimide derivative by fluorescence enhancement in aqueous solution. AB - Naphthalimide derivative (compound 1) containing hydrophilic hexanoic acid group was synthesized and used to recognize Hg(2+) in aqueous solution. The fluorescence enhancement of 1 is attributed to the formation of a complex between 1 and Hg(2+) by 1:1 complex ratio (K=2.08*10(5)), which has been utilized as the basis of fabrication of the Hg(2+)-sensitive fluorescent chemosensor. The comparison of this method with some other fluorescence methods for the determination of Hg(2+) indicated that the method can be applied in aqueous solution rather than organic solution. The analytical performance characteristics of the proposed Hg(2+)-sensitive chemosensor were investigated. The chemosensor can be applied to the quantification of Hg(2+) with a linear range covering from 2.57*10(-7) to 9.27*10(-5) M and a detection limit of 4.93*10(-8) M. The experiment results show that the response behavior of 1 toward Hg(2+) is pH independent in medium condition (pH 4.0-8.0). Most importantly, the fluorescence changes of the chemosensor are remarkably specific for Hg(2+) in the presence of other metal ions, which meet the selective requirements for practical application. Moreover, the response of the chemosensor toward Hg(2+) is fast (response time less than 1 min). In addition, the chemosensor has been used for determination of Hg(2+) in hair samples with satisfactory results, which further demonstrates its value of practical applications. PMID- 22304824 TI - Label-free colorimetric sensing of ascorbic acid based on Fenton reaction with unmodified gold nanoparticle probes and multiple molecular logic gates. AB - A label-free strategy based on Fenton reaction with unmodified gold nanoparticles (AuNPs) as probe is demonstrated for ascorbic acid (AA) sensing. AuNPs is stable in the presence of single stranded DNA (ssDNA) which prevents salt-induced aggregation of AuNPs in solution. The hydroxyl free radicals generated by Fenton reaction lead to ssDNA cleavage into different sequence fragments which induce aggregation of AuNPs to produce a red-to-blue color change. As an efficient biological antioxidant, AA could effectively scavenge free radicals to avoid the cleavage of ssDNA, so that it prevents color change of the AuNPs solution. Thus, the color change of AuNPs in the presence and absence of AA provides a new approach for the detection of AA. The absorbance ratio at two wavelengths, A(670)/A(520), decreases linearly with AA content within 1-15 MUM, giving rise to a detection limit of 0.3 MUM and a RSD of 2.8% (10 MUM). The color display of AuNPs solution makes it feasible for the estimation of AA content by naked eye visualization. Moreover, based on Fenton reaction and unmodified gold nanoparticles, a multiple logic gate system includes two logic operations, i.e., INHIBIT and NOR, has been designed with small molecules (AA, l-cysteine, glutathione) as inputs and the colorimetric changes of AuNPs solution as outputs. PMID- 22304825 TI - Preparation and evaluation of an immunoaffinity sorbent for the analysis of opioid peptides by on-line immunoaffinity solid-phase extraction capillary electrophoresis-mass spectrometry. AB - In this study, we explored a procedure for the preparation of an immunoaffinity (IA) sorbent for the analysis of opioid peptides by on-line immunoaffinity solid phase extraction capillary electrophoresis-mass spectrometry (IA-SPE-CE-MS). We followed a site-specific antibody immobilization approach based on the covalent attachment of the oxidized antibodies through their carbohydrate moieties to hydrazide silica particles, using a polyclonal antibody against Endomorphin 1 and 2 (End1 and End2). The main features of the IA sorbent were studied, such as the amount of hydrazide groups and antibodies attached onto oxidized diol silica particles. Once the procedure was optimized, standard solutions of End1 and End2 were used in order to establish the IA-SPE-CE-MS methodology. Acceptable repeatability, reproducibility and linearity range values were obtained for the proposed methodology. The limits of detection (LODs) of 1 ng mL(-1) were approximately 100-fold better than those obtained by CE-MS. Selectivity of the IA sorbent was good but some cross-reactivity against Dynorphin A (1-7) was observed when a mixture of several opioid peptides was analyzed. Human plasma samples spiked with End1 and End2 were also analyzed and both peptides could be detected down to 100 ng mL(-1). PMID- 22304826 TI - Assessment of trace metal binding kinetics in the resin phase of diffusive gradients in thin films. AB - The dynamic technique of diffusive gradients in thin films (DGT), that measures metal speciation in situ, has found wide environmental application. Simple interpretation of the metal accumulation in terms of a solution concentration has assumed that trace metals do not penetrate beyond the surface of the binding layer, but penetration, although theoretically discussed has not yet been directly measured. Multiple binding layers were used to enable analysis of different depths of a DGT binding phase (Chelex-100 or iminodiacetate resins). In simple metal solution (no ligand) at pH 7, metal penetration to the back layer was low and similar for all metals. However, at lower pH up to 42% of an individual metal accumulated in the back resin layer. This was most noticeable for Mn at pH 4 and 5, but Cd and Co were also affected at pH 4. These results were consistent with rate limited binding, particularly for Mn. A kinetic model successfully fitted the data and allowed derivation of a binding rate constant and the mean distance that metals penetrate into a resin gel (lambda(M)). Only for Mn, Co and Cd were experimentally derived lambda(M) values greater than the diameter of a Chelex-100 resin bead. For most situations, then, the penetration into the binding layer is negligible and binding of trace metal ions can be regarded as instantaneous, validating the simple use and interpretation of DGT. For weakly binding metals at low pH the slower binding allows penetration, which may affect the DGT measurement. PMID- 22304827 TI - Electrical, optical, and docking properties of conical nanopores. AB - The diffusion-influenced translocation behavior of individual nanoparticles upon passage through a conical nanopore has been elucidated by using a pressure reversal, resistive-pulse technique, as reported by Lan and White in this issue of ACS Nano. We outline here some recent progress in conical nanopore analysis, and we present some prospects for future developments. Compared to cylindrical nanopores, the geometric change brought about by tapered nanopores causes a dramatic difference in electrical and optical properties. Such conical nanopores may also be integrated into microfluidic chips to capture cells or nanoparticles, one per nanopore, and then to release them. These advances hold the promise of making conical nanopores useful as highly efficient actuators and sensors. PMID- 22304828 TI - Copper-transporting P-type adenosine triphosphatase (ATP7A) is associated with platinum-resistance in non-small cell lung cancer (NSCLC). AB - BACKGROUND: Copper export protein ATP7A is important for maintaining copper homeostasis. Recent studies have shown that copper transporters are also involved in the transport of platinum. The goal of this study was to determine the role of ATP7A in the platinum-resistance of non-small cell lung cancer (NSCLC). METHODS: Sensitivities to platinums were detected by MTT assay and drug-resistance related genes were analyzed by real-time PCR and immunoblotting between DDP-sensitive A549 and the corresponding DDP-resistant cell subline (A549/DDP). ATP7A expression was evaluated by immunohistochemistry in tumor tissues of unresectable NSCLC patients who received cisplatin-basing chemotherapy. RESULTS: The expression of ATP7A was significantly higher in A549/DDP cell subline than in A549 cells at both mRNA and protein levels. The silencing of ATP7A expression in A549/DDP by siRNA partially reversed DDP-resistance (29.62%) and increased cell apoptosis. ATP7A expression was detected in 41.6%of NSCLC patients, but not in adjacent stroma nor normal lung tissues. ATP7A-positive patients had a significantly poorer histological grade (p = 0.039) and poorer response to platinum-basing chemotherapy (p = 0.001) compared with ATP7A-negative patients. Cox's proportional hazards analysis showed that ATP7A expression was an independent prognostic factor for overall survival (p = 0.045). CONCLUSIONS: ATP7A overexpression played an important role in platinum-resistance of NSCLC, and was a negative prognostic factor of NSCLC patients treated with platinum based chemotherapy. PMID- 22304829 TI - Poor food and nutrient intake among Indigenous and non-Indigenous rural Australian children. AB - BACKGROUND: The purpose of this study was to describe the food and nutrient intake of a population of rural Australian children particularly Indigenous children. Participants were aged 10 to 12 years, and living in areas of relative socio-economic disadvantage on the north coast of New South Wales. METHODS: In this descriptive cross-sectional study 215 children with a mean age of 11.30 (SD 0.04) years (including 82 Indigenous children and 93 boys) completed three 24 hour food recalls (including 1 weekend day), over an average of two weeks in the Australian summer of late 2005. RESULTS: A high proportion of children consumed less than the Australian Nutrient Reference Values for fibre (74-84% less than Adequate Intake (AI)), calcium (54-86% less than Estimated Average Requirement (EAR)), folate and magnesium (36% and 28% respectively less than EAR among girls), and the majority of children exceeded the upper limit for sodium (68-76% greater than Upper Limit (UL)). Energy-dense nutrient-poor (EDNP) food consumption contributed between 45% and 49% to energy. Hot chips, sugary drinks, high-fat processed meats, salty snacks and white bread were the highest contributors to key nutrients and sugary drinks were the greatest per capita contributor to daily food intake for all. Per capita intake differences were apparent by Indigenous status. Consumption of fruit and vegetables was low for all children. Indigenous boys had a higher intake of energy, macronutrients and sodium than non-Indigenous boys. CONCLUSIONS: The nutrient intake and excessive EDNP food consumption levels of Australian rural children from disadvantaged areas are cause for concern regarding their future health and wellbeing, particularly for Indigenous boys. Targeted intervention strategies should address the high consumption of these foods. PMID- 22304830 TI - Commentary on the editorial "Music therapy for dementia". PMID- 22304831 TI - Shear rheology of hard-sphere, dispersed, and aggregated suspensions, and filler matrix composites. AB - This paper reviews the shear rheology of suspensions of microscopic particles. The nature of interparticle forces determines the microstructure, and hence the deformation and flow behavior of suspensions. Consequently, suspensions were classified according to the resulting microstructure: hard-spheres, stabilized, or aggregated particles. This study begins with the most simple case: flowing suspensions of inert, rigid, monomodal spherical particles (called hard-spheres), at low shear rates. Even for inert particles, we reviewed the effect of several factors that produce deviations from this ideal case, namely: shear rate, particle shape, particle size distribution, and particle deformability. Then we moved to suspensions of colloidal particles, where interparticle forces play a significant role. First we studied the case of dispersed or stabilized suspensions (colloidal dispersions), where long range repulsive forces keep particles separated, leading to a crystalline order. Second we studied the more common case of aggregated or flocculated suspensions, where net attractive forces lead to the formation of fractal clusters. Above the gelation concentration (which depends on the magnitude of the attractive forces), clusters are interconnected into a network, forming a gel. We differentiate between weak and strong aggregation, which may lead to weak or strong gels, respectively. Finally, we reviewed the case of filler/matrix composite suspensions or gels, where rigid or viscoelastic particles (fillers) are dispersed in a continuous viscoelastic material (matrix), usually a gel. For each type of suspension, predictive curves of fundamental rheological properties (viscosity, yield stress, elastic and complex moduli) vs. particle volume fraction and shear rate were obtained from theoretical or empirical models and sound experimental data, covering ranges of practical interest. PMID- 22304832 TI - Abl-interactor 2 (ABI2): a novel MLL translocation partner in acute myeloid leukemia. PMID- 22304833 TI - Can the sunshine vitamin melt the fat? PMID- 22304835 TI - Regulation of core clock genes in human islets. AB - Nearly all mammalian cells express a set of genes known as clock genes. These regulate the circadian rhythm of cellular processes by means of negative and positive autoregulatory feedback loops of transcription and translation. Recent genomewide association studies have demonstrated an association between a polymorphism near the circadian clock gene CRY2 and elevated fasting glucose. To determine whether clock genes could play a pathogenetic role in the disease, we examined messenger RNA (mRNA) expression of core clock genes in human islets from donors with or without type 2 diabetes mellitus. Microarray and quantitative real time polymerase chain reaction analyses were used to assess expression of the core clock genes CLOCK, BMAL-1, PER1 to 3, and CRY1 and 2 in human islets. Insulin secretion and insulin content in human islets were measured by radioimmunoassay. The mRNA levels of PER2, PER3, and CRY2 were significantly lower in islets from donors with type 2 diabetes mellitus. To investigate the functional relevance of these clock genes, we correlated their expression to insulin content and glycated hemoglobin levels: mRNA levels of PER2 (rho = 0.33, P = .012), PER3 (rho = 0.30, P = .023), and CRY2 (rho = 0.37, P = .0047) correlated positively with insulin content. Of these genes, expression of PER3 and CRY2 correlated negatively with glycated hemoglobin levels (rho = -0.44, P = .0012; rho = -0.28, P = .042). Furthermore, in an in vitro model mimicking pathogenetic conditions, the PER3 mRNA level was reduced in human islets exposed to 16.7 mmol/L glucose per 1 mmol/L palmitate for 48 hours (P = .003). Core clock genes are regulated in human islets. The data suggest that perturbations of circadian clock components may contribute to islet pathophysiology in human type 2 diabetes mellitus. PMID- 22304834 TI - Novel diagnostics of metabolic dysfunction detected in breath and plasma by selective isotope-assisted labeling. AB - Metabolomics is the study of a unique fingerprint of small molecules present in biological systems under healthy and disease conditions. One of the major challenges in metabolomics is validation of fingerprint molecules to identify specifically perturbed pathways in metabolic aberrations. This step is crucial to the understanding of budding metabolic pathologies and the ability to identify early indicators of common diseases such as obesity, type 2 diabetes mellitus, metabolic syndrome, polycystic ovary syndrome, and cancer. We present a novel approach to diagnosing aberrations in glucose utilization including metabolic pathway switching in a disease state. We used a well-defined prenatally exposed glucocorticoid mouse model that results in adult females with metabolic dysfunction. We applied the complementary technologies of nuclear magnetic resonance spectroscopy and cavity ring-down spectroscopy to analyze serial plasma samples and real-time breath measurements following selective (13)C-isotope assisted labeling. These platforms allowed us to trace metabolic markers in whole animals and identify key metabolic pathway switching in prenatally glucocorticoid treated animals. Total glucose flux is significantly proportionally increased through the major oxidative pathways of glycolysis and the pentose phosphate pathway in the prenatally glucocorticoid-treated animals relative to the control animals. This novel diagnostics approach is fast, noninvasive, and sensitive for determining specific pathway utilization, and provides a direct translational application in the health care field. PMID- 22304836 TI - The effects of daily consumption of grapefruit on body weight, lipids, and blood pressure in healthy, overweight adults. AB - Folklore has suggested that consuming grapefruit may promote weight control. Sparse data exist to support this hypothesis, although there is some evidence of health promotion effects with regard to blood pressure control and modulation of circulating lipids. The aim of this randomized controlled trial was to prospectively evaluate the role of grapefruit in reducing body weight and blood pressure and in promoting improvements in the lipid profile in overweight adults (N = 74). Following a 3-week washout diet low in bioactive-rich fruits and vegetables, participants were randomized to either the control diet (n = 32) or daily grapefruit (n = 42) in the amount of one half of a fresh Rio-Red grapefruit with each meal (3* daily) for 6 weeks. No differences between group in weight, blood pressure, or lipids were demonstrated. Grapefruit consumption was associated with modest weight loss (-0.61 +/- 2.23 kg, P = .097), a significant reduction in waist circumference (-2.45 +/- 0.60 cm, P = .0002), and a significant reduction in systolic blood pressure (-3.21 +/- 10.13 mm Hg, P = .03) compared with baseline values. Improvements were observed in circulating lipids of those consuming grapefruit, with total cholesterol and low-density lipoprotein significantly decreasing by -11.7 mg/dL (P = .002) and -18.7 mg/dL (P < .001), respectively, compared with baseline values. This study suggests that consumption of grapefruit daily for 6 weeks does not significantly decrease body weight, lipids, or blood pressure as compared with the control condition. However, the improvements in blood pressure and lipids demonstrated in the intervention group suggest that grapefruit should be further evaluated in the context of obesity and cardiovascular disease prevention. PMID- 22304837 TI - Human taurine metabolism: fluxes and fractional extraction rates of the gut, liver, and kidneys. AB - Taurine is involved in numerous biological processes. However, taurine plasma level decreases in response to pathological conditions, suggesting an increased need. Knowledge on human taurine metabolism is scarce and only described by arterial-venous differences across a single organ. Here we present taurine organ fluxes using arterial-venous concentration differences combined with blood flow measurements across the 3 major organ systems involved in human taurine metabolism in patients undergoing hepatic surgery. In these patients, we collected blood from an arterial line, portal vein, hepatic vein, and renal vein, and determined blood flow of the hepatic artery, portal vein, and renal vein using Doppler ultrasound. Plasma taurine was determined by high-performance liquid chromatography, and net organ fluxes and fractional extraction rates were calculated. Seventeen patients were studied. No differences were found between taurine concentrations in arterial, portal venous, hepatic venous, and renal venous plasma. The only significant finding was a release of taurine by the portally drained viscera (P = .04). Our data show a net release of taurine by the gut. This probably is explained by the enterohepatic cycle of taurine. Future studies on human taurine metabolism are required to determine whether taurine is an essential aminosulfonic acid during pathological conditions and whether it should therefore be supplemented. PMID- 22304838 TI - The lack of long-range negative correlations in glucose dynamics is associated with worse glucose control in patients with diabetes mellitus. AB - Glucose dynamics measured in ambulatory settings are fluid in nature and exhibit substantial complexity. We recently showed that a long-range negative correlation of glucose dynamics, which is considered to reflect blood glucose controllability over a substantial period, is absent in patients with diabetes mellitus. This was demonstrated using detrended fluctuation analysis (DFA), a modified random-walk analysis method for the detection of long-range correlations. In the present study, we further assessed the relationships between the established clinical indices of glycemic or insulinogenic control of hemoglobin A(1c) (HbA(1c)), glycated albumin (GA), 1,5-anhydroglucitol, and urine C-peptide immunoreactivity and the recently proposed DFA-based indices obtained from continuous glucose monitoring in 104 Japanese diabetic patients. Significant correlations between the following parameters were observed: (1) HbA(1c) and the long-range scaling exponent alpha(2) (r = 0.236, P < .05), (2) GA and alpha(2) (r = 0.254, P < .05), (3) GA and the short-range scaling exponent alpha(1) (r = 0.233, P < .05), and (4) urine C-peptide immunoreactivity and the mean glucose fluctuations (r = 0.294, P < .01). Therefore, we concluded that increases in the long-range DFA scaling exponent, which are indicative of the lack of a long-range negative correlation in glucose dynamics, reflected abnormalities in average glycemic control as clinically determined using HbA(1c) and GA parameters. PMID- 22304839 TI - A review of the role of apolipoprotein C-II in lipoprotein metabolism and cardiovascular disease. AB - The focus of this review is on the role of apolipoprotein C-II (apoC-II) in lipoprotein metabolism and the potential effects on the risk of cardiovascular disease (CVD). We searched PubMed/Scopus for articles regarding apoC-II and its role in lipoprotein metabolism and the risk of CVD. Apolipoprotein C-II is a constituent of chylomicrons, very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein (HDL). Apolipoprotein C-II contains 3 amphipathic alpha-helices. The lipid-binding domain of apoC-II is located in the N-terminal, whereas the C-terminal helix of apoC-II is responsible for the interaction with lipoprotein lipase (LPL). At intermediate concentrations (approximately 4 mg/dL) and in normolipidemic subjects, apoC-II activates LPL. In contrast, both an excess and a deficiency of apoC-II are associated with reduced LPL activity and hypertriglyceridemia. Furthermore, excess apoC-II has been associated with increased triglyceride-rich particles and alterations in HDL particle distribution, factors that may increase the risk of CVD. However, there is not enough current evidence to clarify whether increased apoC-II causes hypertriglyceridemia or is an epiphenomenon reflecting hypertriglyceridemia. A number of pharmaceutical interventions, including statins, fibrates, ezetimibe, nicotinic acid, and orlistat, have been shown to reduce the increased apoC-II concentrations. An excess of apoC-II is associated with increased triglyceride rich particles and alterations in HDL particle distribution. However, prospective trials are needed to assess if apoC-II is a CVD marker or a risk factor in high risk patients. PMID- 22304840 TI - A brief history of insulin resistance: from the first insulin radioimmunoassay to selectively targeting protein kinase C pathways. PMID- 22304841 TI - Vitamin D and insulin sensitivity: can gene association and pharmacogenetic studies of the vitamin D receptor provide clarity? PMID- 22304842 TI - Ankle and midfoot kinetics during normal gait: a multi-segment approach. AB - Multi-segment foot models are increasingly being used to evaluate intra and inter segment foot kinematics such as the motion between the hindfoot/tibia (ankle) and the forefoot/hindfoot (midfoot) during walking. However, kinetic analysis have been mainly restricted to one-segment foot models and could be improved by considering a multi-segment approach. Therefore, the aims of this study were to (1) implement a kinetic analysis of the ankle and theoretical midfoot joints using the existing Oxford Foot Model (OFM) through a standard inverse dynamics approach using only marker, force plate and anthropometric data and (2) to compare OFM ankle joint kinetics to those output by the one-segment foot plugin gait model (PIG). 10 healthy adolescents fitted with both the OFM and PIG markers performed barefoot comfortable speed walking trials over an instrumented walkway. The maximum ankle power generation was significantly reduced by approximately 40% through OFM calculations compared to PIG estimates (p<0.001). This result was not caused by a decrease in OFM computed joint moments, but by a reduction in the angular velocity between the tibia/hindfoot (OFM) compared to the tibia/foot (PIG) (p<0.001). Additionally, analysis revealed considerable midfoot loading. One-segment foot models overestimate ankle power, and may also overestimate the contribution of the triceps surae. A multi-segment approach may help quantify the important contribution of the midfoot ligaments and musculature to power generation. We therefore recommend the use of multi-segment foot models to estimate ankle and midfoot kinetics, especially when surgical decision-making is based on the results of three-dimensional gait analysis. PMID- 22304843 TI - Transducer and base compliance alter the in situ 6 dof force measured from muscle during an isometric contraction in a multi-joint limb. AB - Although musculoskeletal models are commonly used, validating the muscle actions predicted by such models is often difficult. In situ isometric measurements are a possible solution. The base of the skeleton is immobilized and the endpoint of the limb is rigidly attached to a 6-axis force transducer. Individual muscles are stimulated and the resulting forces and moments recorded. Such analyses generally assume idealized conditions. In this study we have developed an analysis taking into account the compliances due to imperfect fixation of the skeleton, imperfect attachment of the force transducer, and extra degrees of freedom (dof) in the joints that sometimes become necessary in fixed end contractions. We use simulations of the rat hindlimb to illustrate the consequences of such compliances. We show that when the limb is overconstrained, i.e., when there are fewer dof within the limb than are restrained by the skeletal fixation, the compliances of the skeletal fixation and of the transducer attachment can significantly affect measured forces and moments. When the limb dofs and restrained dofs are matched, however, the measured forces and moments are independent of these compliances. We also show that this framework can be used to model limb dofs, so that rather than simply omitting dofs in which a limb does not move (e.g., abduction at the knee), the limited motion of the limb in these dofs can be more realistically modeled as a very low compliance. Finally, we discuss the practical implications of these results to experimental measurements of muscle actions. PMID- 22304844 TI - Shape optimization of stress concentration-free lattice for self-expandable Nitinol stent-grafts. AB - In a mechanical component, stress-concentration is one of the factors contributing to reduce fatigue life. This paper presents a design methodology based on shape optimization to improve the fatigue safety factor and increase the radial stiffness of Nitinol self-expandable stent-grafts. A planar lattice free of stress concentrators is proposed for the synthesis of a stent with smooth cell shapes. Design optimization is systematically applied to minimize the curvature and reduce the bending strain of the elements defining the lattice cells. A novel cell geometry with improved fatigue life and radial supportive force is introduced for Nitinol self-expandable stent-grafts used for treating abdominal aortic aneurism. A parametric study comparing the optimized stent-graft to recent stent designs demonstrates that the former exhibits a superior anchoring performance and a reduction of the risk of fatigue failure. PMID- 22304845 TI - The pediatric upper limb motion index and a temporal-spatial logistic regression: quantitative analysis of upper limb movement disorders during the Reach & Grasp Cycle. AB - This study describes a novel pediatric upper limb motion index (PULMI) for children with cerebral palsy (CP). The PULMI is based on three-dimensional kinematics and provides quantitative information about upper limb motion during the Reach & Grasp Cycle. We also report key temporal-spatial parameters for children with spastic, dyskinetic, and ataxic CP. Participants included 30 typically-developing (TD) children (age=10.9+/-4.1 years) and 25 children with CP and upper limb involvement (age=12.3+/-3.7 years), Manual Ability Classification System (MACS) levels I-IV. The PULMI is calculated from the root-mean-square difference for eight kinematic variables between each child with CP and the average TD values, and scaled such that the TD PULMI is 100+/-10. The PULMI was significantly lower among children with CP compared to TD children (Wilcoxon Z= 5.06, p<.0001). PULMI scores were significantly lower among children with dyskinetic CP compared to spastic CP (Z=-2.47, p<.0135). There was a strong negative correlation between PULMI and MACS among children with CP (Spearman's rho=-.78, p<.0001). Temporal-spatial values were significantly different between CP and TD children: movement time (Z=4.06, p<.0001), index of curvature during reach (Z=3.68, p=.0002), number of movement units (Z=3.72, p=.0002), angular velocity of elbow extension during reach (Z=-3.96, p<.0001), and transport(1):reach peak velocities (Z=-2.48, p=.0129). A logistic regression of four temporal-spatial parameters, the Pediatric Upper Limb Temporal-Spatial Equation (PULTSE), correctly predicted 19/22 movement disorder subtypes (spastic versus dyskinetic CP). The PULMI, PULTSE, and key temporal-spatial parameters of the Reach & Grasp Cycle offer a quantitative approach to analyzing upper limb function in children with CP. PMID- 22304846 TI - Effects of obesity on slip-induced fall risks among young male adults. AB - Obesity is associated with structural and functional limitations with impairment of normal gait. Although falls have been identified as the most common cause of injuries in the obese, the mechanisms associated with increased fall risk among the obese population are still unknown. The purpose of this study was to investigate the influence of gait adaptations of the obese individuals and its implication on risk of slip initiations as measured by friction demand characteristics. To exclude the aging and gender effects, a total of ten healthy young male adults participated in the study. Kinematic and kinetic data were collected using a three-dimensional motion analysis system and force plates while subjects were walking at their self-selected walking pace. Results indicated that young obese adults walked similarly as their lean counterparts except for exhibiting greater step width and higher transversal friction demand, suggesting that slip-induced fall risks are similar along the horizontal direction, but increased along the transversal direction under certain floor conditions. PMID- 22304847 TI - Investigation of trypanothione reductase inhibitory activity by 1,3,4 thiadiazolium-2-aminide derivatives and molecular docking studies. AB - The biological activities of a series of mesoionic 1,3,4-thiadiazolium-2-aminide derivatives have been studied. The most active compounds (MI-HH; MI-3-OCH(3); MI 4-OCH(3) and MI-4-NO(2)) were evaluated to determine their effect on trypanothione reductase (TryR) activity in Leishmania sp. and Trypanosoma cruzi. Among the assayed compounds, only MI-4-NO(2) showed enzyme inhibition effect on extracts from different cultures of parasites, which was confirmed using the recombinant enzyme from T. cruzi (TcTryR) and Leishmania infantum (LiTryR). The enzyme kinetics determined with LiTryR demonstrated a non-competitive inhibition profile of MI-4-NO(2). A molecular docking study showed that the mesoionic compounds could effectively dock into the substrate binding site together with the substrate molecule. The mesoionic compounds were also effective ligands of the NADPH and FAD binding sites and the NADPH binding site was predicted as the best of all three binding sites. Based on the theoretical results, an explanation at the molecular level is proposed for the MI-4-NO(2) enzyme inhibition effect. Given TryR as a molecular target, it is important to continue the study of mesoionic compounds as part of a drug discovery campaign against Leishmaniasis or Chagas' disease. PMID- 22304848 TI - Synthesis and biological characterisation of sirtuin inhibitors based on the tenovins. AB - The tenovins are small molecule inhibitors of the NAD(+)-dependent family of protein deacetylases known as the sirtuins. There remains considerable interest in inhibitors of this enzyme family due to possible applications in both cancer and neurodegenerative disease therapy. Through the synthesis of novel tenovin analogues, further insights into the structural requirements for activity against the sirtuins in vitro are provided. In addition, the activity of one of the analogues in cells led to an improved understanding of the function of SirT1 in cells. PMID- 22304849 TI - Synthetic peptides derived from the sequence of a lasso peptide microcin J25 show antibacterial activity. AB - Microcin J25 (MccJ25) is a plasmid-encoded, ribosomally synthesized antibacterial peptide with a unique lasso structure. The lasso structure, produced with the aid of two processing enzymes, provides exceptional stability to MccJ25. We report the synthesis of six peptides (1-6), derived from the MccJ25 sequence, that are designed to form folded conformation by disulfide bond formation and electrostatic or hydrophobic interactions. Two peptides (1 and 6) display good activity against Salmonella newport, and are the first synthetic derivatives of MccJ25 that are bactericidal. Peptide 1 displays potent activity against several Salmonella strains including two MccJ25 resistant strains. The solution conformation and the stability studies of the active peptides suggest that they do not fold into a lasso conformation and peptide 1 displays antimicrobial activity by inhibition of target cell respiration. Like MccJ25, the synthetic MccJ25 derivatives display minimal toxicity to mammalian cells suggesting that these peptides act specifically on bacterial cells. PMID- 22304850 TI - The effect of the length and flexibility of the side chain of basic amino acids on the binding of antimicrobial peptides to zwitterionic and anionic membrane model systems. AB - The intent of this investigation was to determine the effect of varying the side chain length of the basic amino acids residues on the binding of a series of antimicrobial peptides (AMPs) to zwitterionic and anionic LUVs, SUVs and micelles. These AMPs are based on the incorporation of three dipeptide units consisting of the unnatural amino acids Tic-Oic in the sequence, Ac-GF-Tic-Oic-GX Tic-Oic-GF-Tic-Oic-GX-Tic-XXXX-CONH(2), where X (Spacer #2) may be one of the following amino acids, Lys, Orn, Dab, Dpr or Arg. A secondary focus of this study was to attempt to correlate the possible mechanisms of membrane binding of these AMPs to their bacterial strain potency and selectivity. These AMPs produced different CD spectra in the presence of zwitterionic DPC and anionic SDS micelles. This observation indicates that these AMPs adopt different conformations on binding to the surface of zwitterionic and anionic membrane model systems. The CD spectra of these AMPs in the presence of zwitterionic POPC and anionic 4:1 POPC/POPG LUVs and SUVs also were different, indicating that they adopt different conformations on interaction with the zwitterionic and anionic liposomes. This observation was supported by ITC and calcein leakage data that indicated that these AMPs interact via very different mechanisms with anionic and zwitterionic LUVs. The enthalpy for the binding of these AMPs to POPC directly correlates to the length of Spacer #2. The enthalpy of binding of these AMPs to 4:1 POPC/POPG, however do not correlate with the length of Spacer #2. Clear evidence exists that the AMP containing the Dpr residues (the shortest length spacer) interacts very differently with both POPC and 4:1 POPC/POPG LUVs compared to the other four compounds. Data indicates that both the hydrophobicity and the charge distribution of Spacer #2, contribute to defining antibacterial activity. These observations have major implications on the development of these analogs as potential therapeutic agents. PMID- 22304851 TI - Increased endothelial cell selectivity of triazole-bridged dihalogenated A-ring analogues of combretastatin A-1. AB - The antiproliferative activity on ovarian cancer (SK-OV-3) cells of a series of triazole-bridged combretastatin analogues (37, 38, 40-43) containing dihalogenation of the A-ring is reported, and compared with their trimethoxy analogues (5, 15, 39). It was found that dihalogenation with either bromine or iodine was a tolerated modification when compared to the parent compound combretastatin (CA-4, 1) and had less effect than B-ring modification on potency. These compounds exhibited G(2)/M arrest, and maintained antitubulin activity. Further assays on human umbilical vein endothelial cells (HUVECs) demonstrated the potential antivascular effects of these triazoles. Of particular note was a 3,5-diiodo-4-methoxyaryl triazole (43) which had promising 7-fold selectivity for HUVECs over ovarian cancer cells. PMID- 22304852 TI - Tracking cellular-level enamel growth and structure in 4D with synchrotron imaging. PMID- 22304853 TI - Assessment of ventricular contractility and ventricular-arterial coupling with a model-based sensor. AB - Estimation of ventricular contractility and ventricular arterial coupling is clinically important in diagnosing and treating cardiac dysfunction in the critically ill. However, experimental assessment of indexes of ventricular contractility, such as the end-systolic pressure-volume relationship, requires a highly invasive maneuver and measurements that are not typical in an intensive care unit (ICU). This research describes the use of a previously validated cardiovascular system model and parameter identification process to evaluate the right ventricular arterial coupling in septic shock. Model-based ventricular arterial coupling is defined by the ratio of the end systolic right ventricular elastance (E(esrvf)) over the pulmonary artery elastance (E(pa)) or the mean pulmonary inflow resistance (R(pulin)). Results are compared to the clinical gold standard assessment (conductance catheter method). Six anesthetized healthy pigs weighing 20-30kg received a 0.5mg kg(-1) endotoxin infusion over a period of 30min from T0 to T30, to induce septic shock and veno-venous hemofiltration was used from T60 onward. The results show good agreement with the gold-standard experimental assessment. In particular, the model-based right ventricular elastance (E(esrvf)) correlates well with the clinical gold standard (R(2)=0.69) and the model-based non-invasive coupling (E(esrvf)/R(pulin)) follow the same trends and dynamics (R(2)=0.37). The overall results show the potential to develop a model-based sensor to monitor ventricular-arterial coupling in clinical real-time. PMID- 22304854 TI - A child with severe pneumomediastinum and ABCA3 gene mutation: a puzzling connection. PMID- 22304855 TI - Closure of a fistula in the main bronchus after pneumonectomy with an Occlutech Figulla Flex ASD. PMID- 22304856 TI - Effects of sunlight and diet on vitamin D status of pulmonary tuberculosis patients in Tbilisi, Georgia. AB - OBJECTIVE: Vitamin D deficiency is common in tuberculosis (TB) and this may modulate immune responses. This study investigated vitamin D status in patients with TB and examined the sources of vitamin D in Tbilisi, Georgia. METHODS: We measured plasma 25-hydroxyvitamin D (25[OH]D) and dietary vitamin D intake in patients with pulmonary TB (n = 85) in Tbilisi, Georgia. To determine the impact of season on vitamin D status, we tested the in vitro conversion of 7 dehydrocholesterol (7-DHC) to previtamin D(3) after sunlight exposure. RESULTS: In subjects with TB, mean plasma 25(OH)D concentrations were 14.4 +/- 7.0 ng/mL, and vitamin D insufficiency (25[OH]D <30 ng/mL) occurred in 97% of subjects. The dietary sources of vitamin D were mainly fish, eggs, and butter. The daily intake was well below recommended daily intakes in subjects with TB (172 +/- 196 IU). The conversion of 7-DHC to previtamin D(3) was undetectable from October to March and highest in June and July from 11:00 to 14:00 h. CONCLUSION: An insufficient vitamin D dietary intake and a limited production of vitamin D from sunlight for most of the year may explain the high prevalence of vitamin D insufficiency in patients with TB in Tbilisi. PMID- 22304858 TI - Weight gain in long-term survivors of kidney or liver transplantation--another paradigm of sarcopenic obesity? AB - OBJECTIVE: Obesity in transplant recipients is a frequent phenomenon but data from body composition analyses in long-term survivors are limited. Body composition and energy metabolism were studied in patients after liver (LTX) and kidney (KTX) transplantation and patients with liver cirrhosis (LCI) or on chronic hemodialysis (HD) and compared to healthy controls. METHODS: In 42 patients 50.0 mo (median; range 17.1-100.6) after LTX and 30 patients 93.0 mo (31.2-180.1) after KTX as wells as in LCI (n = 39) or HD (n = 10) patients mid arm muscle and fat area, body cell mass, and phase angle (bioimpedance analysis), and resting energy expenditure (indirect calorimetry, REE(CALO)) were measured. RESULTS: Obesity was more prevalent in LTX (17%) than LCI (3%) and in KTX (27%) than in HD (10%). In LTX and KTX, phase angle was higher than in end-stage disease (LTX 5.6 degrees [4.1-7.2] versus LCI 4.4 degrees [2.9-7.3], P < 0.001; KTX 5.9 degrees [4.4-8.7] versus HD 4.3 degrees [2.9-6.8]) but was lower in all patient groups than in controls (7.1 degrees ; 4.6-8.9; P < 0.001). In LCI and HD REE(CALO) was higher than predicted, while in LTX and KTX REE(CALO) was not different from predicted REE. CONCLUSIONS: Despite excellent graft function, many long-term LTX or KTX survivors exhibit a phenotype of sarcopenic obesity with increased fat but low muscle mass. This abnormal body composition is observed despite normalization of the hypermetabolism found in chronic disease and cannot be explained by overeating. The role of appropriate nutrition and physiotherapy after transplantation merits further investigation. PMID- 22304857 TI - High-sugar intake does not exacerbate metabolic abnormalities or cardiac dysfunction in genetic cardiomyopathy. AB - OBJECTIVE: A high-sugar intake increases heart disease risk in humans. In animals, sugar intake accelerates heart failure development by increased reactive oxygen species (ROS). Glucose-6-phosphate dehydrogenase (G6PD) can fuel ROS production by providing reduced nicotinamide adenine dinucleotide phosphate (NADPH) for superoxide generation by NADPH oxidase. Conversely, G6PD also facilitates ROS scavenging using the glutathione pathway. We hypothesized that a high-sugar intake would increase flux through G6PD to increase myocardial NADPH and ROS and accelerate cardiac dysfunction and death. METHODS: Six-week-old TO-2 hamsters, a non-hypertensive model of genetic cardiomyopathy caused by a delta sarcoglycan mutation, were fed a long-term diet of high starch or high sugar (57% of energy from sucrose plus fructose). RESULTS: After 24 wk, the delta sarcoglycan-deficient animals displayed expected decreases in survival and cardiac function associated with cardiomyopathy (ejection fraction: control 68.7 +/- 4.5%, TO-2 starch 46.1 +/- 3.7%, P < 0.05 for TO-2 starch versus control; TO 2 sugar 58.0 +/- 4.2%, NS, versus TO-2 starch or control; median survival: TO-2 starch 278 d, TO-2 sugar 318 d, P = 0.133). Although the high-sugar intake was expected to exacerbate cardiomyopathy, surprisingly, there was no further decrease in ejection fraction or survival with high sugar compared with starch in cardiomyopathic animals. Cardiomyopathic animals had systemic and cardiac metabolic abnormalities (increased serum lipids and glucose and decreased myocardial oxidative enzymes) that were unaffected by diet. The high-sugar intake increased myocardial superoxide, but NADPH and lipid peroxidation were unaffected. CONCLUSION: A sugar-enriched diet did not exacerbate ventricular function, metabolic abnormalities, or survival in heart failure despite an increase in superoxide production. PMID- 22304859 TI - Pepsinogen I/II ratio is related to glucose, triacylglycerol, and uric acid levels. AB - OBJECTIVE: Under- and overnutrition are associated with a worse prognosis and constitute independent risk factors for morbidity and mortality. It is increasingly important to understand the factors that affect nutritional and metabolic statuses. The purpose of this study was to assess the relation between the pepsinogen I/II ratio and several biochemical markers. METHODS: A cross sectional study was performed in 1985 subjects who underwent a health screening test. Subjects had no medications for hyperuricemia, dyslipidemia, diabetes mellitus, or hypertension. All subjects were classified into two groups. Subjects with a pepsinogen I/II ratio below 3 were defined as having atrophic gastritis. The relations between the pepsinogen I/II ratio and several biochemical markers, including total cholesterol, triacylglycerol, uric acid, cholinesterase, and glucose levels, were evaluated. RESULTS: The presence of atrophic gastritis was significantly associated with age, smoking status, alcohol consumption, body mass index, and triacylglycerol, uric acid, cholinesterase, and hemoglobin levels. Multiple linear regression analysis demonstrated that the pepsinogen I/II ratio was an independent determinant of glucose level (beta = 0.104, P < 0.0001), triacylglycerol level (beta = 0.072, P = 0.0014), uric acid level (beta = 0.048, P = 0.0138), and hemoglobin (beta = 0.037, P = 0.0429) after adjustments for age, sex, smoking status, alcohol consumption, and body mass index. CONCLUSION: The pepsinogen I/II ratio was related to glucose, triacylglycerol, and uric acid levels. Such an association fosters the idea that a decreased pepsinogen I/II ratio seems favorable for the prevention of overnutrition. PMID- 22304860 TI - Obesity: from the agricultural revolution to the contemporary pediatric epidemic. AB - Obesity is pandemic in Western society. Currently, approximately 100 million Americans are overweight (body mass index > 25 kg/m2) or obese (body mass index > 30 kg/m2). The pandemic is largely attributable to the relatively recent (from an evolutionary perspective) adoption of a sedentary lifestyle, coupled with the high availability of foods with high caloric content in Western cultures. These factors superimposed on dated genotypes have given rise to the global obesity epidemic. Over the past two decades, the discovery of leptin and other new molecules (e.g., adiponectin, resistin, ghrelin) has shed significant light on the pathophysiologic mechanisms of obesity-related morbidities, many of which became apparent through human epidemiologic studies during the last half of the 20th century. Of high concern for modern Western societies is the pediatric obesity epidemic, which stands to cripple Western cultures, both literally and financially in terms of health care costs and exhaustion of finite medical resources. The prevalence of childhood obesity has more than tripled since the 1960s, and 12.5 million (~17%) of children and teenagers are obese in the United States today. The rate of increasing prevalence of childhood obesity is staggering, and the collective efforts of the pediatric medical community and scientists are essential for battling the epidemic. PMID- 22304861 TI - Preoperative cardiac evaluation and perioperative cardiac therapy in patients undergoing open surgery for abdominal aortic aneurysms: effects on cardiovascular outcome. AB - BACKGROUND: Cardiovascular complications, such as death, myocardial infarction, or heart failure, are the leading causes of morbidity and mortality in adult patients undergoing major noncardiac surgery. OBJECTIVE: To evaluate the effects of an accurate preoperative cardiac evaluation, together with optimized perioperative drug therapy, in reducing cardiovascular events in patients undergoing open aortic surgery for abdominal aneurysm. METHODS: Between January 2000 and December 2008, we considered all consecutive patients undergoing elective abdominal aortic open surgery at the Vascular Surgery Unit of the University of Study-Spedali Civili (Italy). Since January 2003, we have used an intensive cardiac preoperative evaluation: patients with at least one cardiac risk factor received a preoperative cardiac evaluation; all non-invasive and invasive tests were performed preoperatively when indicated by the consultant cardiologist, that also optimized the pharmacological perioperative therapy. The outcome of the 418 patients undergoing surgery between 2003 and 2008 was compared with those of the 204 patients in the previous triennium 2000 to 2002, when only patients with positive history for cardiac disease received a standard preoperative cardiological clinical or instrumental evaluation. RESULTS: Patients enrolled in the 2003 to 2008 interval were slightly older and with a higher prevalence of comorbidities compared with those observed in the previous triennium; furthermore, the number of noninvasive tests performed before surgery increased significantly. Nevertheless, the number of major cardiac perioperative complications decreased over time: particularly, in-hospital mortality rate was 0.9% in the latter period, compared with 3.4% in the years 2000 to 2002. Also, the long-term mortality was significantly reduced in patients operated on between 2003 and 2008 compared with those operated on in the previous triennium. CONCLUSION: These data suggest a significant benefit of an intensive cardiac preoperative evaluation in reducing the incidence of perioperative and postoperative cardiac morbidity and mortality. PMID- 22304862 TI - The results of a needs assessment to guide a vascular surgery skills simulation curriculum. AB - BACKGROUND: In response to economic and societal pressures, a new integrated model of vascular surgery training has emerged that will condense training into 5 years. These new requirements challenge educators to develop innovative training programs that produce competent surgeons despite time constraints. Surgical skills simulation is a proven effective method to teach and evaluate learners in surgery residency programs. METHODS: To determine which skills are the most important to include in a vascular surgical skills training curriculum, a needs assessment survey was administered to all attending surgeons and fellows at vascular surgery training institutions in Southern California. Participants were asked to rank 52 vascular procedures and skills on a Likert scale (with scores ranging from 1 [not necessary] to 5 [essential]) based on perceived need for simulation training. RESULTS: Nineteen (48.7%) surveys were returned (6 fellows [60%], 13 attending surgeons [44.8%]). Carotid artery stenting was ranked by both fellows and attendings as the most essential procedure for simulation, with a mean score of 4.26. This was followed by open repair of ruptured infrarenal aortic aneurysm (R-AAA) (3.79), renal angioplasty/stent (3.68), thoracic endovascular aortic aneurysm repair (3.53), and open repair of juxtarenal/suprarenal aortic aneurysm (3.47). In addition, fellows gave a rank of 4 or higher to R-AAA, thoracic endovascular aortic aneurysm repair, mesenteric artery angioplasty/bypass, renal angioplasty/stent, and intravascular ultrasonography. Attendings did not give a mean rank score of 4 or higher to any procedures other than carotid artery stenting. CONCLUSIONS: Our needs assessment identified vascular procedures where simulation may be beneficial to improve the skill level of vascular trainees in Southern California. With economic and logistical constraints for simulation at each individual training facility, a potential approach to this educational challenge is a regional Southern California vascular surgery skills simulation center. PMID- 22304863 TI - Pedicled flaps in association with distal bypass for lower-limb salvage. AB - BACKGROUND: After distal bypass for limb salvage, persistence of large ischemic ulcers with exposure of tendons, joints, and bone and secondary graft exposure can lead to amputation, even though the bypass remains patent. Coverage of such defects using free flaps is too lengthy and complex for use in elderly patients. Although quick and simple, pedicled flaps are often considered to be contraindicated in patients with occlusive artery disease. The purpose of this study was to evaluate the outcome of pedicled flaps harvested after evaluation of revascularized territories on angiograms for coverage of tissue defects. METHODS: From 1994 to 2000, a total of 23 pedicled flap procedures were performed in 22 patients with a mean age of 75 years (range, 54-91 years). The distal anastomosis of the bypass was located on a tibial or pedal artery in 19 cases and on the popliteal artery in 4. The indication for flap placement was chronic ulcer in 7 cases, secondary graft exposure in 15, and open fracture with acute ischemia in 1. To be considered as usable, the flap had to be vascularized by a pedicle fed by the bypassed artery and have a rotational axis sufficient to cover the defect. Muscle flaps were used in 11 cases, fasciocutaneous flaps in 10, and fascial flaps in 2. RESULTS: The flap procedures in this study led to primary healing in 17 cases, secondary healing in 4 cases, and failure due to necrosis in 2. Follow up examination was carried out with Doppler ultrasonography at 1, 6, and 12 months and every 6 months thereafter. The mean follow-up period was 23 months (range, 3-5 years). Statistical analysis demonstrated bypass patency, limb salvage, and survival rates in agreement with those previously reported in the literature. CONCLUSIONS: Our results suggest that pedicle flaps are feasible after distal bypass in patients with lower-extremity occlusive artery disease. This technique expands the indication for limb salvage with low morbidity. PMID- 22304864 TI - Matrine inhibits disturbed flow-enhanced migration via downregulation of ERK1/2 MLCK signaling vascular smooth muscle cells. AB - BACKGROUND: To investigate the effects of matrine on the vascular smooth muscle cell (VSMC) migration modulated by disturbed flow and their underlying molecular mechanisms in vitro. METHODS: Isolated rat aortic VSMCs were grown to confluence on 20- * 80-mm fibronectin-coated glass cover slides, and then, denuded zones were made at the position calculated to be the oscillating flow-reattachment zone and also in the downstream laminar flow region. VSMCs were treated with different doses of matrine (0, 10, 20, 30, and 40 mg/L), or PD98059 (30 MUM), ML-7 (10 MUM) combined with matrine (40 mg/L) for 30 minutes before and during the experiments. Then, the wounded monolayers were kept under static conditions or were subjected to laminar or disturbed flow for 21 hours or 10 hours. The VSMC migration was assessed by microscopic images. The extracellular signal-regulated kinase 1/2 (ERK1/2) and myosin light chain kinase (MLCK) proteins were determined by Western blot. RESULTS: Disturbed flow significantly increased phosphorylation of ERK1/2. Selective inhibition of ERK1/2 phosphorylation by inhibitor PD98059 and matrine significantly suppressed VSMC migration under disturbed flow. Disturbed flow significantly enhanced phosphorylation of MLCK, whereas both matrine and PD98059 inhibited the phosphorylation of MLCK under disturbed flow. The complete inhibition of MLCK phosphorylation using the selective MLCK inhibitor ML-7 significantly inhibited VSMC migration under disturbed flow. CONCLUSION: Matrine inhibits VSMC migration under disturbed flow, in part, by downregulation of ERK1/2-MLCK signaling pathway. PMID- 22304865 TI - Aortic endograft infection with aortoduodenal fistula associated with adjacent vertebral body mycobacterial osteomyelitis (Pott's disease). AB - Aortoenteric fistulas (AEFs) are a rare complication of infrarenal abdominal aortic aneurysm repair. They occur in <1% of aortic grafting procedures, result from graft defects, foreign bodies, and trauma, and are associated with a high mortality rate. We report a complex AEF associated with vertebral body osteomyelitis, likely secondary to tuberculous infection. A 78-year-old man presented with a 2-week history of abdominal pain, fever, and anemia. Past surgical history is significant for open repair of infrarenal abdominal aortic aneurysm followed later by an endovascular repair of a proximal para-anastomotic aneurysm. Computed tomography angiography revealed air in the aneurysm sac, without evidence of endoleak. The posterior aspect of the aneurysm was noted to be in continuity with a destructive osteomyelitis of the second lumbar vertebral body and an adjacent psoas abscess. Percutaneous drainage revealed purulent fluid containing mixed enteric flora. With fluoroscopic guidance, injection of contrast in the aortic sac drainage catheter demonstrated complex fistulous communications from the aortic sac to the overlying small intestine. After a course of drainage, antibiotic therapy, and parenteral nutrition, the patient underwent a transperitoneal repair of the AEF with duodeno-duodenectomy and wide debridement of the aortic sac and Dacron graft. Pathology revealed giant cell granulomas, highly suggestive of tuberculosis. PMID- 22304866 TI - Anatomic bifurcated reconstruction of chronic bilateral innominate-superior vena cava occlusion using the Y-stenting technique. AB - This article presents the case of a 42-year-old man who presented with superior vena cava (SVC) syndrome due to fibrosing mediastinitis with multiple failed attempts at recanalization. We initially treated him with unilateral sharp needle recanalization of the right innominate vein into the SVC stump followed by stenting. Although his symptoms improved immediately, they did not completely resolve. Six months later, he returned with worsening symptoms, and venography revealed in-stent restenosis. The patient requested simultaneous treatment on the left side. The right stent was dilated, and a 3-cm-long occlusion of the left innominate vein was recanalized, again using sharp needle technique, homing into the struts of the right-sided stent. Following fenestration of the stent, a second stent was deployed from the left side into the SVC, and the two Y limbs were sequentially dilated to allow a true bifurcation anatomy (figure). The patient had complete resolution of his symptoms and continues to do well 6 months later. PMID- 22304867 TI - Bilateral femoral artery aneurysm mimicking soft tissue sarcoma. AB - Despite the rarity of femoral aneurysm and the plethora of other causes of swelling in and around its anatomic location, the possibility of its existence must always be borne in mind. A rare case of metachronously bilateral femoral aneurysms mimicking soft tissue sarcoma in a young Nigerian man is presented. Caution in the diagnosis of groin masses is hereby re-emphasized. PMID- 22304868 TI - Giant, metachronous bilateral dorsalis pedis artery true aneurysms. AB - This report is the first to describe the clinical, radiographic, operative, and pathologic findings associated with large, bilateral dorsalis pedis artery true aneurysms in a single patient. A 61-year-old African American woman complained of difficulty in wearing shoes. She had a moderately firm, nontender, pulsatile mass on the dorsum of her right foot. Computed tomography and angiography confirmed dorsalis pedis artery aneurysm with sufficient collateralization. She underwent resection without reconstruction. Pathologic analysis revealed a true aneurysm (8 * 5.3 * 4.1 cm(3)) containing intralumenal thrombus. Treatment for small symptomatic and large dorsalis pedis artery aneurysms remains resection with or without reconstruction. PMID- 22304869 TI - Infected abdominal aneurysm due to Salmonella sepsis: report of a unique case treated using the superficial femoral vein. AB - We describe a 61-year-old patient with an infected aneurysm of the abdominal aorta due to Salmonella sepsis. Treatment was successful and included aneurysm resection, extensive debridement, and reconstruction of the abdominal aorta using the superficial femoral vein, combined with long-term antibiotic therapy. PMID- 22304870 TI - Delayed axillary artery pseudoaneurysm as an isolated consequence to anterior dislocation of the shoulder. AB - Injury to the axillary artery after anterior shoulder dislocation is a very rare occurrence; although infrequently seen as an iatrogenic complication, very few cases have been reported. We describe a case of delayed axillary artery pseudoaneurysm, presenting as single complication after anterior shoulder dislocation reduction, which was successfully managed by surgical intervention resection-anastomosis. Although uncommon, pseudoaneurysms should not be forgotten after trivial trauma. The early diagnosis of upper-limb pseudoaneurysms should prevent the risk of vascular and neurological compromises with potential serious long-term sequelae. PMID- 22304871 TI - Clostridium septicum aortitis with associated sigmoid colon adenocarcinoma. AB - We report an unusual case of Clostridium septicum aortitis with associated adenocarcinoma of the sigmoid colon. An 87-year-old man with multiple medical comorbidities presented with a 1-week history of severe abdominal pain in the left lower quadrant of his abdomen. Abdominal computed tomography showed, in addition to a mass in the sigmoid colon, a gas density within the wall of the abdominal aorta with extensive periaortic fat stranding and some additional gas densities in the proximal left common iliac artery. The patient refused surgery, and was treated with intravenous antibiotics. He died 5 weeks later. The development of Clostridiumsepticum aortitis, an extremely rare but life threatening infection, is highly associated with an underlying colonic malignancy and demands immediate surgical intervention. PMID- 22304872 TI - Successful treatment for infected aortic aneurysm using endovascular aneurysm repairs as a bridge to delayed open surgery. AB - Management of infected aortic aneurysms, which can be life-threatening, remains challenging. Open surgical treatments, including debridement of the infected aorta and the surrounding tissue and either in situ reconstruction or extra anatomic bypass covering with omentum or muscle flap, are the mainstay of therapy. However, increasing advances in technology have made endovascular treatment of infected aneurysms feasible. The present study describes the first clinical report of successful treatment of an infected aneurysm using endovascular techniques in the acute phase, followed by delayed open surgery. PMID- 22304873 TI - Effect of surveillance method on reported characteristics of Lyme disease, Connecticut, 1996-2007. AB - To determine the effect of changing public health surveillance methods on the reported epidemiology of Lyme disease, we analyzed Connecticut data for 1996 2007. Data were stratified by 4 surveillance methods and compared. A total of 87,174 reports were received that included 79,896 potential cases. Variations based on surveillance methods were seen. Cases reported through physician-based surveillance were significantly more likely to be classified as confirmed; such case-patients were significantly more likely to have symptoms of erythema migrans only and to have illness onset during summer months. Case-patients reported through laboratory-based surveillance were significantly more likely to have late manifestations only and to be older. Use of multiple surveillance methods provided a more complete clinical and demographic description of cases but lacked efficiency. When interpreting data, changes in surveillance method must be considered. PMID- 22304874 TI - Universal processes and common factors in couple therapy and relationship education. AB - Across nearly all cultures, sharing a lifelong committed relationship with an intimate partner comprises an almost universal and strongly held ambition. Nevertheless, cross-national data reliably indicate a high prevalence of relationship distress and dissolution, with adverse emotional and physical health consequences for adult partners and their children. This introduction to the special section summarizes findings regarding the effectiveness of couple therapy for treating general relationship distress, couple-based interventions for individual mental or physical health problems, and couple relationship education programs aimed at helping couples sustain a healthy committed relationship. Within each of these approaches, evidence regarding potential mediators of interventions' effectiveness is reviewed, and critical unanswered questions are highlighted. Discussion concludes with a brief introduction to each of the articles comprising this special section on universal processes in couple therapy and relationship education. PMID- 22304875 TI - Integrative approaches to couple therapy: implications for clinical practice and research. AB - Although meta-analyses affirm that various treatments for couple distress produce statistically and clinically significant outcomes, research findings also indicate that a large percentage of couples fail to benefit or subsequently deteriorate following current therapies. Based on these findings, we advocate potential advantages of integrative approaches to couple therapy. We distinguish among assimilative, transtheoretical, and pluralistic approaches to integration and describe exemplars of each. Integrative approaches to couple therapy are compared to distillatory or common factors approaches emphasizing common elements of treatment components, therapist characteristics, and client or relationship attributes. We argue that clinical practice of integrative approaches to couple therapy requires conceptual and clinical decision-making skills transcending those of any one theoretical modality and emphasizing the selection, sequencing, and pacing of diverse interventions in a coherent manner. We conclude with implications of integrative couple-based treatments for future research. PMID- 22304876 TI - Common principles of couple therapy. AB - The similarity in efficacy of evidence-based couple therapies suggests that it may be useful to identify those treatment principles they hold in common. Expanding on the previous description of a unified protocol for couple therapy (Christensen, 2010), this article outlines five common principles: (a) altering the couple's view of the presenting problem to be more objective, contextualized, and dyadic; (b) decreasing emotion-driven, dysfunctional behavior; (c) eliciting emotion-based, avoided, private behavior; (d) increasing constructive communication patterns; and (e) emphasizing strengths and reinforcing gains. For each of these five elements of the unified protocol, the paper addresses how and to what extent the most common forms of evidence-based couple therapy carry out this principle. Implications for clinical practice, treatment research, and basic research on intimate relationships are discussed. PMID- 22304877 TI - Common factors of change in couple therapy. AB - Though it is clear from meta-analytic research that couple therapy works well, it is less clear how couple therapy works. Efforts to attribute change to the unique ingredients of a particular model have consistently turned up short, leading many researchers to suggest that change is due to common factors that run through different treatment approaches and settings. The purpose of this article is to provide an empirically based case for several common factors in couple therapy, and discuss clinical, training, and research implications for a common factors couple therapy paradigm. Critical distinctions between model-driven and common factors paradigms are also discussed, and a moderate common factors approach is proposed as a more useful alternative to an extreme common factors approach. PMID- 22304878 TI - Toward making progress feedback an effective common factor in couple therapy. AB - Systematic monitoring of individual therapy progress, coupled with feedback to the therapist, reliably enhances therapy outcome by alerting therapists to individual clients who are off track to benefit by the end of therapy. The current paper reviews the possibility of using similar systematic monitoring and feedback of therapy progress as a means to enhance couple therapy outcome, including what measures of therapy progress are most likely to be useful, how to structure feedback to be most useful to therapists, and the likely mediators of the effects of therapy progress feedback. One implicit assumption of therapy progress feedback is that clients unlikely to benefit from therapy can be detected early enough in the course of therapy for corrective action to be taken. As a test of this assumption, midtherapy progress was examined as a predictor of final couple therapy outcome in a sample of 134 distressed couples. Either a brief 7- or 32-item assessment of couple therapy progress at midtherapy detected a substantial proportion (46%) of couples who failed to benefit by the end of therapy. Given that failure to benefit from couple therapy is somewhat predictable across the course of therapy, future research should test whether systematic monitoring and feedback of progress could enhance therapy outcome. PMID- 22304879 TI - Couple-based interventions for medical problems. AB - The current paper discusses general principles, therapeutic strategies, common factors, and domains commonly addressed in the treatment of couples who have a partner with a medical condition. Couple-based interventions for medical problems are contrasted with couple therapy and relationship education in that the emphasis is on assisting the patient in addressing the medical disorder, along with being attentive to the patient's partner and their relationship. Guidelines are provided showing how knowledge and understanding of medical disorders and couple functioning are integrated in order to conduct such interventions. Five common domains addressed during intervention are elaborated upon: (a) psychoeducation about the disorder, (b) sharing thoughts and feeling regarding the disorder, (c) making decisions focal to the medical disorder, (d) implementing relationship changes that are nonmedical but that result from the disorder, and (e) addressing relationship functioning unrelated to the disorder. The importance of empirically demonstrating the utility of each domain in future investigations is noted. PMID- 22304880 TI - Exploring programmatic moderators of the effectiveness of marriage and relationship education programs: a meta-analytic study. AB - This study uses meta-analytic methods to explore programmatic moderators or common factors of the effectiveness of marriage and relationship education (MRE) programs. We coded 148 evaluation reports for potential programmatic factors that were associated with stronger intervention effects, although the range of factors we could code was limited by the lack of details in the reports. Overall, we found a positive effect for program dosage: moderate-dosage programs (9-20 contact hours) were associated with stronger effects compared to low-dosage programs (1-8 contact hours). A programmatic emphasis on communication skills was associated with stronger effects on couple communication outcomes, but this difference did not reach statistical significance for the relationship quality/satisfaction outcome. There was no evidence that institutionalized MRE programs (formal manuals, ongoing presence, formal instructor training, multiple evaluations) were associated with stronger effects. Similarly, there was little evidence of differences in program setting (university/laboratory vs. religious). We discuss possible explanations for these findings and implications for program design and evaluation. PMID- 22304881 TI - Common factors in the enhancement of dyadic coping. AB - Stress and coping are important constructs in understanding the dynamics of close relationships. Couple therapy and marital distress prevention approaches have become increasingly focused on these variables to gain knowledge of how stress and coping may impact the quality and stability of close relationships. In this paper, we outline couple's coping enhancement training (CCET) and the coping oriented couple's therapy (COCT); both, couple interventions derived from stress and coping research. We address specific features of each approach and report data on their efficacy and effectiveness. We also examine both the common and specific factors that may play a role in the effectiveness of these approaches. PMID- 22304882 TI - Where's the action? Understanding what works and why in relationship education. AB - The field of couples relationship education has come to a critical junction. We have generally demonstrated that our interventions work (at least in the short run) but to what extent have we shown that the skills and processes we teach are in fact responsible for the success of the intervention? In this paper we review progress made in understanding mechanisms of change in relationship education, explore limitations of this body of research, explicate the barriers that interfere with progress in understanding mechanisms of change in intervention research, and present recommendations on how to proceed from here. Although our goal in this paper is to focus more on issues in the field rather than to present a comprehensive review of the literature, we provide overarching research summaries to illustrate some of our points. We conclude with offering recommendations for the next generation of research in the couples relationship education field. PMID- 22304883 TI - How can we improve preventive and educational interventions for intimate relationships? AB - Improving intimate relationships with preventive and educational interventions has proven to be more difficult than originally conceived, and earlier models and approaches may be reaching their limits. Basic concerns remain about the long term effectiveness of these interventions, whether they are reaching and benefiting couples most likely to need them, and how they might be exerting their effects. We identify six problems that we believe are hindering progress in the field, and for each we outline research findings that point to new ways forward. These problems include (a) the incomplete understanding of couple communication and unwarranted translation of communication findings into interventions; (b) the surprising stability of relationship satisfaction; (c) the powerful roles that personal histories, personalities, and stress play in determining relationship outcomes; (d) the difficulties involved in recruiting and retaining high-risk couples in intervention programs; (e) the lack of attention given to specific stages of relationship development in interventions; and (f) the tendency to deliver preventive and educational interventions in the same format as therapies for distressed couples. We conclude by noting that a large body of basic research about intimate relationships, and large-scale outcome research with diverse populations, hold great promise for advancing the field. PMID- 22304884 TI - What, why, and for whom: couples interventions: a deconstruction approach. AB - This paper provides a commentary on the special series on universal processes and common factors in couple therapy (Halford & Snyder, this issue). The authors in this section share their insights, from varying perspectives, about what it is in couples therapy and relationship education programs that work, why they work, and for whom they work best. In so doing, these articles address specific elements of couples interventions--in effect, taking a couples approach apart in order to understand it better. However, as a collection, this section takes this approach to understanding one step further. It puts the elements back together again, making the process of couples therapy/relationship education more accessible and easier to customize based upon the couple, the presenting complaints, the therapist, and the context. The term "deconstruction" is used to describe how the specific elements of couples interventions are understood and reassembled in new, theoretical, and empirically validated ways. It is argued here that once it is understood that a couples intervention works, why it works, and for whom it works, we are able to individualize our approach to specific couples in an effort to make couples therapy better at improving relationships and keeping them improved. PMID- 22304885 TI - Effects of experienced disgust on habituation during repeated exposure to threat relevant stimuli in blood-injection-injury phobia. AB - Despite growing evidence implicating disgust in the etiology of blood-injection injury (BII) phobia, the relevance of disgust for exposure-based treatment of BII phobia remains largely unknown. Individuals with BII phobia were randomly assigned to a disgust (view vomit videos) or neutral activation (view waterfall videos) condition. They were then exposed to 14 videotaped blood draws, during which fear and disgust levels were repeatedly assessed. Participants then engaged in a behavioral avoidance test (BAT) consisting of exposure to threat-relevant stimuli. Examination of outcome comparing the identical first and last blood-draw clips revealed that fear and disgust toward blood draws was significantly reduced in both groups. Disgust levels were also found to be more intense for the video stimuli relative to fear levels whereas the opposite was true for BAT stimuli. Contrary to predictions, the disgust induction did not enhance reductions in negative responses to the target video or reduce behavioral avoidance. Growth curve analyses did show that individuals with BII phobia exposed to the disgust induction showed greater initial fear levels during repeated exposure than those in the neutral condition. However, this effect was not consistently observed across different analytic approaches. Changes in fear during exposure were also found to be independent of changes in disgust but not vice versa, and greater initial fear levels during repeated exposure to threat was associated with fear and disgust levels during the BAT. The implications of these findings for conceptualizing the role of disgust in etiology and treatment of BII phobia are discussed. PMID- 22304886 TI - The effect of communication deficits on anxiety symptoms in infants and toddlers with autism spectrum disorders. AB - Autism spectrum disorders (ASDs) are life-long developmental disorders characterized by impairments in the development of reciprocal social and communication skills, abnormal language development, and a restricted repertoire of behaviors and interests. While it has been known for some time that children with ASD can evince elevated rates of anxiety symptoms, little research has been conducted on whether deficits in communication skills affect the range of anxiety symptoms in infants and toddlers with ASD. This study represents a first attempt to determine whether deficits in communication skills have an effect on the expression of anxiety in infants and toddlers with autistic disorder and pervasive developmental disorder-not otherwise specified. Seven hundred thirty five infants were evaluated with respect to the nature and extent of anxiety symptoms and developmental functioning. Both receptive and expressive communication skills appeared to play a significant role in the manifestation of anxiety symptoms. PMID- 22304887 TI - The impact of an 8-day intensive treatment for adolescent panic disorder and agoraphobia on comorbid diagnoses. AB - Previous research findings have shown positive effects of cognitive-behavioral therapy for primary anxiety disorders as well as for nonprimary, co-occurring anxiety disorders. In this study, we analyzed data from an existing randomized controlled trial of intensive treatment for panic disorder with or without agoraphobia (PDA) to examine the effects of the treatment on comorbid psychiatric diagnoses. The overall frequency and severity of aggregated comorbid diagnoses decreased in a group of adolescents who received an 8-day treatment for PDA. Results suggest that an 8-day treatment for PDA can alleviate the symptoms of some specific comorbid clinical diagnoses; in particular specific phobias, generalized anxiety disorder, and social phobia. These findings suggest that an intensive treatment for PDA is associated with reductions in comorbid symptoms even though disorders other than PDA are not specific treatment targets. PMID- 22304888 TI - The effects of cognitive behavior therapy delivered by students in a psychologist training program: an effectiveness study. AB - Relatively little is known about the efficacy of clinically inexperienced student therapists carrying out cognitive behavior therapy (CBT) under supervision during a professional, psychologist training program. The current study evaluated this by collecting pre- and posttreatment data on 591 consecutive patients receiving treatment at the Psychotherapy Clinic of the Department of Psychology, Stockholm University, Sweden, over an 8-year period. The patients had mainly anxiety disorders or depression with a mean duration of 15 years, and received individual CBT for a mean of 18 sessions. They improved significantly on both general measures (Beck Anxiety Inventory [BAI], Beck Depression Inventory [BDI], and Quality of Life Inventory [QOLI]) and disorder-specific self-report scales. The proportions of recovered patients on the BAI (63%) and the BDI (60%) were higher than those of a comparison effectiveness study. On the specific self-report scales the current sample improved as much as the samples in extant efficacy trials. We conclude that clinically inexperienced student therapists who receive supervision from experienced supervisors can achieve treatment effects that are on a par with those of experienced licensed psychotherapists. PMID- 22304889 TI - Interoceptive fear conditioning and panic disorder: the role of conditioned stimulus-unconditioned stimulus predictability. AB - Interoceptive fear conditioning is at the core of contemporary behavioral accounts of panic disorder. Yet, to date only one study has attempted to evaluate interoceptive fear conditioning in humans (see Acheson, Forsyth, Prenoveau, & Bouton, 2007). That study used brief (physiologically inert) and longer-duration (panicogenic) inhalations of 20% CO(2)-enriched air as an interoceptive conditioned (CS) and unconditioned (US) stimulus and evaluated fear learning in three conditions: CS only, CS-US paired, and CS-US unpaired. Results showed fear conditioning in the paired condition, and fearful responding and resistance to extinction in an unpaired condition. The authors speculated that such effects may be due to difficulty discriminating between the CS and the US. The aims of the present study are to (a) replicate and expand this line of work using an improved methodology, and (b) clarify the role of CS-US discrimination difficulties in either potentiating or depotentiating fear learning. Healthy participants (N=104) were randomly assigned to one of four conditions: (a) CS only, (b) contingent CS US pairings, (c) unpaired CS and US presentations, or (d) an unpaired "discrimination" contingency, which included an exteroceptive discrimination cue concurrently with CS onset. Electrodermal and self-report ratings served as indices of conditioned responding. Consistent with expectation, the paired contingency and unpaired contingencies yielded elevated fearful responding to the CS alone. Moreover, adding a discrimination cue to the unpaired contingency effectively attenuated fearful responding. Overall, findings are consistent with modern learning theory accounts of panic and highlight the role of interoceptive conditioning and unpredictability in the etiology of panic disorder. PMID- 22304890 TI - Scrupulosity in Islam: a comparison of highly religious Turkish and Canadian samples. AB - Scrupulosity is a form of obsessive-compulsive disorder (OCD) characterized by a tendency to have persistent doubts about God, sin, and the adequacy of one's religious behaviors and devotion. To date, no published studies have compared scrupulosity in high- and low-religious Muslim and Christian samples. In the present study religious school students as well as high- and low-religious university students in Turkey and Canada were compared on the Penn Inventory of Scrupulosity (PIOS), Obsessive Beliefs Questionnaire (OBQ-44), and symptom measures of obssesionality and negative affect. Between-group comparisons revealed that the highly religious Turkish sample scored significantly higher than the highly religious Canadian students on the PIOS Fear of God but not the Fear of Sin subscale. Separate multiple regression analyses revealed that the Clark-Beck Obsessive Compulsive Inventory (CBOCI) Obsessions subscale, OBQ-44 Importance and Control of Thoughts subscale, and guilt were significant unique predictors of PIOS scrupulosity. These findings suggest that subtle differences exist in how scrupulosity is manifested in Islamic and Christian believers. PMID- 22304891 TI - The role of "interoceptive" fear conditioning in the development of panic disorder. AB - More than 20% of the general population experience a panic attack at least once in their lives; however, only a minority goes on to develop panic disorder (PD). Conditioning mechanisms have been proposed to explain this evolution in persons who are susceptible to developing panic disorder upon a "traumatic" panic attack. According to preparedness theory, some cues are more likely to condition than others, namely, those referring to internal, bodily signals of danger. The aim of the present study was to test this theory in a differential conditioning paradigm, making use of scripts referring to different internal, bodily sensations as conditioned stimulus (CS) and inhalation of 35% CO(2) as unconditioned stimulus (UCS). Thirty-three healthy volunteers were assigned to three scripts conditions: "suffocation," "neutral," or "urgency." During acquisition, one of two versions of a particular script was always followed by an inhalation of 35% CO(2) (CS+) and the other by room air (CS-). Acquisition was followed by a test phase, where only inhalations of room air were administered. In line with our hypothesis, only participants in the suffocation condition exhibited a selective conditioning effect. They were more fearful and showed a significantly higher increase in tidal volume than participants in the two control conditions. Results are discussed with relation to interoceptive conditioning, preparedness, and the possible role of tidal volume in PD. PMID- 22304892 TI - Couple therapy for military veterans: overall effectiveness and predictors of response. AB - Despite the numerous challenges facing U.S. veterans and their relationships, there have been no examinations of the effectiveness of couple therapy for relationship distress provided to veterans. In the present study, 177 couples presenting for couple therapy at two Veteran Administration Medical Centers completed assessments of relationship satisfaction prior to therapy and weekly during therapy. Results revealed that the average couple showed significant gains in relationship satisfaction during treatment (d=0.44 for men; d=0.47 for women); gains were larger for couples beginning therapy in the distressed range (d=0.61 for men; d=0.58 for women) than for couples in the nondistressed range (d=0.19 for men; d=0.22 for women). Rates of premature termination were high, with 19% of couples completing fewer than three sessions and 62% rated as not completing a "full course" of therapy. Benchmarking analyses demonstrated that the average gains were larger than would be expected from natural remission and similar to previous effectiveness trials; however, average gains were smaller than those observed in couple therapy efficacy trials. Relationship, psychological, and demographic characteristics were generally unrelated to the amount of change in therapy after controlling for initial satisfaction. However, African American couples showed significantly larger gains than Caucasian, non-Hispanic couples. Thus, though yielding smaller effects than those shown in efficacy trials, the impact of couple therapy for veterans' relationship problems appears to generalize across various demographic, psychological, and relationship characteristics. PMID- 22304893 TI - Salivary pH as a marker of plasma adiponectin concentrations in Women. AB - BACKGROUND: Plasma adiponectin is a significant correlate of the pro-inflammatory cardiometabolic risk profile associated with obesity and type 2 diabetes. Salivary pH is influenced by several cardiometabolic risk components such as inflammation, oxidation and numerous oral and systemic health modulators, including the menopausal status. This study aimed to assess the association between plasma adiponectin concentrations and salivary pH in women according to the menopausal status. METHOD: Unstimulated saliva collection was performed in 151 Caucasian women of French-Canadian origin (53 premenopausal women (PMW) and 98 menopausal women (MW)). Student's t test, ANOVA and linear regression models were used to assess the association between plasma adiponectin concentrations and salivary pH. RESULTS: Plasma adiponectin levels increased as a function of salivary pH in the whole sample and among MW (r = 0.29 and r = 0.36, p < 0.001). The proportion of the variance of plasma adiponectin levels explained by the salivary pH (R2) was 10.8% (p < 0.001). Plasma adiponectin levels progressively increased across salivary pH quartiles (p = 0.005). CONCLUSIONS: These results suggest that salivary pH is a significant correlate of plasma adiponectin levels in women. With the increasing prevalence of type 2 diabetes and obesity, new technologies should be developed to more easily monitor health status, disease onset and progression. Salivary pH, a simple, inexpensive and non-invasive measure, could be a very promising avenue. PMID- 22304894 TI - Bio-packaged transponder MEMS implanted in rats. AB - A novel hydroxyapatite-based hybrid material with controlled porosity was designed as a bio-package to implant micro-electro-mechanical systems (MEMS) in living organisms. The biomaterial was prepared using synthetic stoichiometric hydroxyapatite powder reacted with a chemical-active, solvent-free, alkyd-based polyurethane. This porous material has interconnected pores with sizes between 100 and 350 MUm and a pore volume fraction of 50%, fulfilling the requirements for implants. The biomaterial additionally has high wearing resistance and hydrolytic stability providing high endurance properties. The bio-package was characterized mechanically and morphologically using X-ray diffraction, scanning electron microscopy, densitometry, abrasion and mechanical tests. Twelve packaged micro-electro-mechanical systems were implanted subcutaneously into rats and tested for up to 9 months with good acceptance as revealed by the histological analysis performed on the soft tissue surrounding each implant. PMID- 22304895 TI - Clogging influence on metals migration and removal in sub-surface flow constructed wetlands. AB - Chromium (Cr) and Nickel (Ni) removal from secondary effluent has been evaluated in a four year research program to determine the effectiveness of Sub-Surface Flow (SSF) Constructed Wetlands (cw(s)). Tests were performed in small scale (10 l/h) and full scale (150 m(3)/d) SSF cw(s). Metals removal was also assessed as a function of increased clogging that occurred in the cw(s) over the course of the study. Cr and Ni content were evaluated in sediments at various locations along the flow path and in plant tissues by sampling Phragmites australis roots, stems and leaves. Clogging was evaluated by measuring hydraulic conductivity at the same sampling locations at the beginning and at the end of the experiment. Residence Time Distribution (RTD) curves were also assessed at the beginning and after 48months; the skewness of the RTDs increased over this period. Proportionality between increasing clogging and sediment accumulation of metals was observed, especially for Ni. Adsorption to the original matrix and the accumulated sediment is a removal mechanism consistent with available data. PMID- 22304896 TI - Enhancement of anti-murine colon cancer immunity by fusion of a SARS fragment to a low-immunogenic carcinoembryonic antigen. AB - BACKGROUND: It is widely understood that tumor cells express tumor-associated antigens (TAAs), of which many are usually in low immunogenicity; for example, carcinoembryonic antigen (CEA) is specifically expressed on human colon cancer cells and is viewed as a low-immunogenic TAA. How to activate host immunity against specific TAAs and to suppress tumor growth therefore becomes important in cancer therapy development. RESULTS: To enhance the immune efficiency of CEA in mice that received, we fused a partial CEA gene with exogenous SARS-CoV fragments. Oral vaccination of an attenuated Salmonella typhimurium strain transformed with plasmids encoding CEA-SARS-CoV fusion gene into BALB/c mice elicited significant increases in TNF-alpha and IL-10 in the serum. In addition, a smaller tumor volume was observed in CT26/CEA-bearing mice who received CEA SARS-CoV gene therapy in comparison with those administered CEA alone. CONCLUSION: The administration of fusing CEA-SARS-CoV fragments may provide a promising strategy for strengthening the anti-tumor efficacy against low immunogenic endogenous tumor antigens. PMID- 22304897 TI - 1918 influenza, a puzzle with missing pieces. PMID- 22304899 TI - Bartonella and Bartonella infections in China: from the clinic to the laboratory. AB - The current status of Bartonella studies in mainland China is reviewed including both laboratory and ecological data and limited clinical data. Detection and isolation of Bartonella species from arthropods, pets and small wild animals is commonplace; this includes a variety of known and emerging Bartonella pathogens. In contrast, the medical literature analyzed from 1980 to 2010 consists of 31 reports of only of cat scratch disease (CSD). Most cases are from the East and South-Eastern provinces, the most populated areas with best access to medical care. Disease typically is described as febrile illness with symptoms traditionally reported for CSD elsewhere in the world. Clinical observations and anamnesis are the primary bases for diagnosis, since specialized serologic and molecular diagnosis is not widely available. Seroprevalence of healthy populations determined using Bartonella henselae antigen varies from 9.6 to 19.6%. The apparent discordance postulated between possible environmental exposure to diverse Bartonella agents and restricted B. henselae case etiologies suggests a need to determine whether other Bartonella species may also be etiologic agents of human illness and emphasizes the importance of applying modern diagnostic tools widely in clinical practice in mainland China. PMID- 22304898 TI - The influence of cattle breed on susceptibility to bovine tuberculosis in Ethiopia. AB - Bovine tuberculosis in domestic livestock such as cattle is an economically important disease with zoonotic potential, particularly in countries with emerging economies. We discuss the findings of recent epidemiological and immunological studies conducted in Ethiopia on host susceptibility differences between native zebu and the exotic Holstein-Friesian cattle that are increasingly part of the Ethiopian National herd, due to the drive to increase milk yields. These findings support the hypothesis that native Zebu cattle are more resistant to bovine tuberculosis. We also summarise the results of experimental infections that support the epidemiological data, and of laboratory experiments that suggest a role for the innate immune response, and in particular interleukin-6, in the outcome of bovine tuberculosis infection. PMID- 22304900 TI - Immunological characterization of Mycoplasma hyopneumoniae recombinant proteins. AB - Mycoplasma hyopneumoniae, the primary pathogen of enzootic pneumonia, is highly prevalent worldwide and causes major economic losses to the pig industry. Commercial vaccines are widely used in the control of this disease, however, they provide only partial protection. The aim of this study was to evaluate 34 recombinant proteins of M. hyopneumoniae expressed in Escherichia coli. Antigenic and immunogenic properties of these proteins were analyzed. For this, the proteins were tested against hyperimmune and convalescent pig sera through ELISA and Western blot. Immunogenicity of the recombinant proteins was evaluated in BALB/c mice following intramuscular inoculation. Most antigens were able to induce a strong immune response and sera from inoculated mice were able to recognize native proteins by cell ELISA and Western blot. Several recombinant proteins were specifically recognized by convalescent pig sera, indicating they are expressed during infection. These data may help to develop more efficacious vaccines against M. hyopneumoniae. PMID- 22304901 TI - The 48th annual meeting of the International Association of Forensic Toxicologists (TIAFT). Joint meeting with the Society of Toxicological and Forensic Chemistry (GTFCh). Editorial. PMID- 22304902 TI - Salpingectomy for ectopic pregnancy by transumbilical single-site laparoscopy with the SILS system. AB - OBJECTIVE: To evaluate the feasibility in everyday practice and the advantages of salpingectomy for ectopic pregnancy by single-incision laparoscopic surgery with the SILS system. STUDY DESIGN: This single-center prospective observational study included 37 women requiring salpingectomy for ectopic pregnancy who underwent single-incision laparoscopic salpingectomy with the SILS system. Information about feasibility and intra- and post-operative data were collected. The data for these patients were compared with those of a control group of 40 women treated by standard laparoscopy. RESULTS: Thirty-six (97%) patients were treated successfully with the SILS system. After laparoscopic confirmation of the ectopic pregnancy, salpingectomy was performed with bipolar forceps and scissors. In one case, conversion to classic laparoscopy was performed because SILS was not feasible. Compared with the control group, operative time was longer (50 +/- 35 vs 35 +/- 30 min, p=0.001) but duration of hospitalization shorter with single site laparoscopy (1.5 +/- 1.5 vs 2.3 +/- 1.5 days, p=0.02). CONCLUSIONS: Laparoscopic salpingectomy for ectopic pregnancy appears to be feasible in everyday practice by single-incision laparoscopic surgery with the SILS system and appears to reduce the duration of hospitalization. Larger series are necessary to confirm this conclusion. PMID- 22304903 TI - Low back pain in 17 year olds has substantial impact and represents an important public health disorder: a cross-sectional study. AB - BACKGROUND: Prevalence of low back pain (LBP) rises rapidly during adolescence, reaching adult levels by the age of 18. It has been suggested that adolescent LBP is benign with minimal impact, despite limited evidence. METHODS: The aim of this study was to investigate the impact of LBP and the influence of chronicity, gender and presence of other spinal pain comorbidities at age 17. Subjects (n=1283) were categorised according to experiencing current and chronic LBP, gender and presence of other areas of spinal pain. LBP impact was ascertained via questions regarding seeking professional assistance, using medication, missing school/work, limited normal or recreational physical activity and health related quality of life (HRQOL). RESULTS: 12.3% of participants reported current but not chronic LBP, while 19.9% reported current chronic LBP. LBP was more commonly reported by females than males. Other spinal pain comorbidities were common in the LBP groups. Impact was greater in subjects with chronic LBP, in females and in those with other spinal pain comorbidities. CONCLUSION: LBP, and particularly chronic LBP, has a significant negative impact at 17 years. It is commonly associated with care seeking, medication use, school absenteeism, and reduced HRQOL. These findings support that adolescent LBP is an important public health issue that requires attention. PMID- 22304904 TI - Transcatheter valve-in-valve implantation for deteriorated aortic bioprosthesis: initial clinical results and follow-up in a series of high-risk patients. AB - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become a viable alternative in maximum risk patients. For those patients requiring aortic valve re-replacement, the "valve-in-valve" concept has been described. We report our experience with transapical valve-in-valve implantation in 7 patients with deteriorated aortic bioprosthesis at 1-year follow up. METHODS: Since November 2008, 210 patients received transapical TAVI due to severe aortic stenosis. Seven patients presented with deteriorated aortic valve bioprosthesis and received transapical valve-in-valve implantation. Mean age was 78.7+/-0.8 years. Preoperatively, all patients were at New York Heart Association (NYHA) functional class III. For risk estimation, the Society of Thoracic Surgeons (STS) and European System for Cardiac Operative Risk Evaluation (ES) risk scores were used and predicted high mortality (means+/-standard error of the mean: STSMortality 21.6+/-2.8%, ESadd 14.9+/-1.1, ESlog 52.6+/-9.0%). Mean follow-up time was 517+/ 65 days (range, 280 to 799 days). RESULTS: Six patients showed a severely deteriorated bioprosthesis in terms of a stenotic valve (aortic valve area: 0.64+/-0.04 cm2, maximum/mean developed transvalvular pressure gradient: dPmax 63.3+/-10.9 mm Hg, dPmean 40.4+/-5.6 mm Hg). One patient's deteriorated prosthesis was highly insufficient. Procedural success rate was 100%, mean procedure time was 46.7+/-12.3 minutes. Echocardiography revealed excellent hemodynamics of implanted prosthesis (dPmax 31.1+/-5.5 mm Hg; dPmean 19.4+/-4.3 mm Hg). Overall, postoperative course was uneventful. No patient died during follow-up, which ranged up to 26 months. All patients, except 1, remained in NYHA class I or II. CONCLUSIONS: Our results demonstrate feasibility and safety of the transapical valve-in-valve approach with excellent hemodynamic and clinical results. Decision making in a multidisciplinary setting is mandatory. Further studies with more patients and longer follow-up are needed to identify candidates benefiting from transapical transcatheter valve-in-valve implantation. PMID- 22304906 TI - Finding a target for resveratrol. AB - Despite resveratrol's well-documented health benefits, its mechanism of action remains controversial. In particular, the direct molecular target of resveratrol has been elusive. Park et al. now show that resveratrol directly inhibits cAMP dependent phosphodiesterases, triggering a cascade of events that converge on the important energy-sensing metabolic regulators AMPK, SIRT1, and PGC-1alpha. PMID- 22304907 TI - Innate immunity to TB: a druggable balancing act. AB - Tobin and colleagues show that both inhibition and excessive production of the inflammatory mediator TNFalpha impact the pathogenesis of tuberculosis (TB) and the response to therapy. Identifying a critical role for the genetically determined balance between pro- and anti-inflammatory eicosanoids in regulating TNFalpha levels provides a roadmap to tailored TB treatment based on host genotype. PMID- 22304908 TI - Immune cells exploit a neural circuit to enter the CNS. AB - Multiple sclerosis (MS) is associated with the appearance of autoreactive T cells in the central nervous system. Using a mouse model of MS, Arima et al. now show that this attack begins at a specific spinal cord location. T cell entry into the CNS is regulated by a reflex neural circuit originating from leg muscle contractions. PMID- 22304909 TI - A new histone at the centromere? AB - The centromere is a classic system to study epigenetic specification, and most research has focused on a specialized histone variant, CENP-A, that is required for kinetochore assembly. Now Nishino et al. reveal a new level of complexity for centromeric chromatin, by showing that the kinetochore complex CENP-T-W-S-X shares structural and functional properties with canonical histones. PMID- 22304910 TI - FGF21 and the second coming of PPARgamma. AB - Peptide hormone fibroblast growth factor-21 (FGF21) has insulin-mimetic properties. Dutchak et al. now suggest that FGF21 also acts in an autocrine fashion in adipocytes and is required to mediate effects of the PPARgamma agonist class of antidiabetic drugs. Does this new property improve FGF21's fledgling clinical prospects or endorse a clinical resuscitation of PPARgamma agonists? PMID- 22304911 TI - Hypoxia-inducible factors in physiology and medicine. AB - Oxygen homeostasis represents an organizing principle for understanding metazoan evolution, development, physiology, and pathobiology. The hypoxia-inducible factors (HIFs) are transcriptional activators that function as master regulators of oxygen homeostasis in all metazoan species. Rapid progress is being made in elucidating homeostatic roles of HIFs in many physiological systems, determining pathological consequences of HIF dysregulation in chronic diseases, and investigating potential targeting of HIFs for therapeutic purposes. PMID- 22304912 TI - The genetic basis for cancer treatment decisions. AB - Personalized cancer medicine is based on increased knowledge of the cancer mutation repertoire and availability of agents that target altered genes or pathways. Given advances in cancer genetics, technology, and therapeutics development, the timing is right to develop a clinical trial and research framework to move future clinical decisions from heuristic to evidence-based decisions. Although the challenges of integrating genomic testing into cancer treatment decision making are wide-ranging and complex, there is a scientific and ethical imperative to realize the benefits of personalized cancer medicine, given the overwhelming burden of cancer and the unprecedented opportunities for advancements in outcomes for patients. PMID- 22304913 TI - Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. AB - Resveratrol, a polyphenol in red wine, has been reported as a calorie restriction mimetic with potential antiaging and antidiabetogenic properties. It is widely consumed as a nutritional supplement, but its mechanism of action remains a mystery. Here, we report that the metabolic effects of resveratrol result from competitive inhibition of cAMP-degrading phosphodiesterases, leading to elevated cAMP levels. The resulting activation of Epac1, a cAMP effector protein, increases intracellular Ca(2+) levels and activates the CamKKbeta-AMPK pathway via phospholipase C and the ryanodine receptor Ca(2+)-release channel. As a consequence, resveratrol increases NAD(+) and the activity of Sirt1. Inhibiting PDE4 with rolipram reproduces all of the metabolic benefits of resveratrol, including prevention of diet-induced obesity and an increase in mitochondrial function, physical stamina, and glucose tolerance in mice. Therefore, administration of PDE4 inhibitors may also protect against and ameliorate the symptoms of metabolic diseases associated with aging. PMID- 22304914 TI - Host genotype-specific therapies can optimize the inflammatory response to mycobacterial infections. AB - Susceptibility to tuberculosis is historically ascribed to an inadequate immune response that fails to control infecting mycobacteria. In zebrafish, we find that susceptibility to Mycobacterium marinum can result from either inadequate or excessive acute inflammation. Modulation of the leukotriene A(4) hydrolase (LTA4H) locus, which controls the balance of pro- and anti-inflammatory eicosanoids, reveals two distinct molecular routes to mycobacterial susceptibility converging on dysregulated TNF levels: inadequate inflammation caused by excess lipoxins and hyperinflammation driven by excess leukotriene B(4). We identify therapies that specifically target each of these extremes. In humans, we identify a single nucleotide polymorphism in the LTA4H promoter that regulates its transcriptional activity. In tuberculous meningitis, the polymorphism is associated with inflammatory cell recruitment, patient survival and response to adjunctive anti-inflammatory therapy. Together, our findings suggest that host-directed therapies tailored to patient LTA4H genotypes may counter detrimental effects of either extreme of inflammation. PMID- 22304915 TI - Regional neural activation defines a gateway for autoreactive T cells to cross the blood-brain barrier. AB - Although it is believed that neural activation can affect immune responses, very little is known about the neuroimmune interactions involved, especially the regulators of immune traffic across the blood-brain barrier which occurs in neuroimmune diseases such as multiple sclerosis (MS). Using a mouse model of MS, experimental autoimmune encephalomyelitis, we show that autoreactive T cells access the central nervous system via the fifth lumbar spinal cord. This location is defined by IL-6 amplifier-dependent upregulation of the chemokine CCL20 in associated dorsal blood vessels, which in turn depends on gravity-induced activation of sensory neurons by the soleus muscle in the leg. Impairing soleus muscle contraction by tail suspension is sufficient to reduce localized chemokine expression and block entry of pathogenic T cells at the fifth lumbar cord, suggesting that regional neuroimmune interactions may offer therapeutic targets for a variety of neurological diseases. PMID- 22304916 TI - A transcription factor collective defines cardiac cell fate and reflects lineage history. AB - Cell fate decisions are driven through the integration of inductive signals and tissue-specific transcription factors (TFs), although the details on how this information converges in cis remain unclear. Here, we demonstrate that the five genetic components essential for cardiac specification in Drosophila, including the effectors of Wg and Dpp signaling, act as a collective unit to cooperatively regulate heart enhancer activity, both in vivo and in vitro. Their combinatorial binding does not require any specific motif orientation or spacing, suggesting an alternative mode of enhancer function whereby cooperative activity occurs with extensive motif flexibility. A fraction of enhancers co-occupied by cardiogenic TFs had unexpected activity in the neighboring visceral mesoderm but could be rendered active in heart through single-site mutations. Given that cardiac and visceral cells are both derived from the dorsal mesoderm, this "dormant" TF binding signature may represent a molecular footprint of these cells' developmental lineage. PMID- 22304917 TI - CENP-T-W-S-X forms a unique centromeric chromatin structure with a histone-like fold. AB - The multiprotein kinetochore complex must assemble at a specific site on each chromosome to achieve accurate chromosome segregation. Defining the nature of the DNA-protein interactions that specify the position of the kinetochore and provide a scaffold for kinetochore formation remain key goals. Here, we demonstrate that the centromeric histone-fold-containing CENP-T-W and CENP-S-X complexes coassemble to form a stable CENP-T-W-S-X heterotetramer. High-resolution structural analysis of the individual complexes and the heterotetramer reveals similarity to other histone fold-containing complexes including canonical histones within a nucleosome. The CENP-T-W-S-X heterotetramer binds to and supercoils DNA. Mutants designed to compromise heterotetramerization or the DNA protein contacts around the heterotetramer strongly reduce the DNA binding and supercoiling activities in vitro and compromise kinetochore assembly in vivo. These data suggest that the CENP-T-W-S-X complex forms a unique nucleosome-like structure to generate contacts with DNA, extending the "histone code" beyond canonical nucleosome proteins. PMID- 22304918 TI - Cortical dynein controls microtubule dynamics to generate pulling forces that position microtubule asters. AB - Dynein at the cortex contributes to microtubule-based positioning processes such as spindle positioning during embryonic cell division and centrosome positioning during fibroblast migration. To investigate how cortical dynein interacts with microtubule ends to generate force and how this functional association impacts positioning, we have reconstituted the 'cortical' interaction between dynein and dynamic microtubule ends in an in vitro system using microfabricated barriers. We show that barrier-attached dynein captures microtubule ends, inhibits growth, and triggers microtubule catastrophes, thereby controlling microtubule length. The subsequent interaction with shrinking microtubule ends generates pulling forces up to several pN. By combining experiments in microchambers with a theoretical description of aster mechanics, we show that dynein-mediated pulling forces lead to the reliable centering of microtubule asters in simple confining geometries. Our results demonstrate the intrinsic ability of cortical microtubule-dynein interactions to regulate microtubule dynamics and drive positioning processes in living cells. PMID- 22304919 TI - A structure-based mechanism for Arf1-dependent recruitment of coatomer to membranes. AB - Budding of COPI-coated vesicles from Golgi membranes requires an Arf family G protein and the coatomer complex recruited from cytosol. Arf is also required with coatomer-related clathrin adaptor complexes to bud vesicles from the trans Golgi network and endosomal compartments. To understand the structural basis for Arf-dependent recruitment of a vesicular coat to the membrane, we determined the structure of Arf1 bound to the gammazeta-COP subcomplex of coatomer. Structure guided biochemical analysis reveals that a second Arf1-GTP molecule binds to betadelta-COP at a site common to the gamma- and beta-COP subunits. The Arf1 binding sites on coatomer are spatially related to PtdIns4,5P(2)-binding sites on the endocytic AP2 complex, providing evidence that the orientation of membrane binding is general for this class of vesicular coat proteins. A bivalent GTP dependent binding mode has implications for the dynamics of coatomer interaction with the Golgi and for the selection of cargo molecules. PMID- 22304920 TI - PKCepsilon promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. AB - The transcription factor ATF2 elicits oncogenic activities in melanoma and tumor suppressor activities in nonmalignant skin cancer. Here, we identify that ATF2 tumor suppressor function is determined by its ability to localize at the mitochondria, where it alters membrane permeability following genotoxic stress. The ability of ATF2 to reach the mitochondria is determined by PKCepsilon, which directs ATF2 nuclear localization. Genotoxic stress attenuates PKCepsilon effect on ATF2; enables ATF2 nuclear export and localization at the mitochondria, where it perturbs the HK1-VDAC1 complex; increases mitochondrial permeability; and promotes apoptosis. Significantly, high levels of PKCepsilon, as seen in melanoma cells, block ATF2 nuclear export and function at the mitochondria, thereby attenuating apoptosis following exposure to genotoxic stress. In melanoma tumor samples, high PKCepsilon levels associate with poor prognosis. Overall, our findings provide the framework for understanding how subcellular localization enables ATF2 oncogenic or tumor suppressor functions. PMID- 22304921 TI - Fibroblast growth factor-21 regulates PPARgamma activity and the antidiabetic actions of thiazolidinediones. AB - Fibroblast growth factor-21 (FGF21) is a circulating hepatokine that beneficially affects carbohydrate and lipid metabolism. Here, we report that FGF21 is also an inducible, fed-state autocrine factor in adipose tissue that functions in a feed forward loop to regulate the activity of peroxisome proliferator-activated receptor gamma (PPARgamma), a master transcriptional regulator of adipogenesis. FGF21 knockout (KO) mice display defects in PPARgamma signaling including decreased body fat and attenuation of PPARgamma-dependent gene expression. Moreover, FGF21-KO mice are refractory to both the beneficial insulin-sensitizing effects and the detrimental weight gain and edema side effects of the PPARgamma agonist rosiglitazone. This loss of function in FGF21-KO mice is coincident with a marked increase in the sumoylation of PPARgamma, which reduces its transcriptional activity. Adding back FGF21 prevents sumoylation and restores PPARgamma activity. Collectively, these results reveal FGF21 as a key mediator of the physiologic and pharmacologic actions of PPARgamma. PMID- 22304922 TI - Ret is a multifunctional coreceptor that integrates diffusible- and contact-axon guidance signals. AB - Growing axons encounter multiple guidance cues, but it is unclear how separate signals are resolved and integrated into coherent instructions for growth cone navigation. We report that glycosylphosphatidylinositol (GPI)-anchored ephrin-As function as "reverse" signaling receptors for motor axons when contacted by transmembrane EphAs present in the dorsal limb. Ephrin-A receptors are thought to depend on transmembrane coreceptors for transmitting signals intracellularly. We show that the receptor tyrosine kinase Ret is required for motor axon attraction mediated by ephrin-A reverse signaling. Ret also mediates GPI-anchored GFRalpha1 signaling in response to GDNF, a diffusible chemoattractant in the limb, indicating that Ret is a multifunctional coreceptor for guidance molecules. Axons respond synergistically to coactivation by GDNF and EphA ligands, and these cooperative interactions are gated by GFRalpha1 levels. Our studies uncover a hierarchical GPI-receptor signaling network that is constructed from combinatorial components and integrated through Ret using ligand coincidence detection. PMID- 22304923 TI - Visualizing neuromodulation in vivo: TANGO-mapping of dopamine signaling reveals appetite control of sugar sensing. AB - Behavior cannot be predicted from a "connectome" because the brain contains a chemical "map" of neuromodulation superimposed upon its synaptic connectivity map. Neuromodulation changes how neural circuits process information in different states, such as hunger or arousal. Here we describe a genetically based method to map, in an unbiased and brain-wide manner, sites of neuromodulation under different conditions in the Drosophila brain. This method, and genetic perturbations, reveal that the well-known effect of hunger to enhance behavioral sensitivity to sugar is mediated, at least in part, by the release of dopamine onto primary gustatory sensory neurons, which enhances sugar-evoked calcium influx. These data reinforce the concept that sensory neurons constitute an important locus for state-dependent gain control of behavior and introduce a methodology that can be extended to other neuromodulators and model organisms. PMID- 22304924 TI - Modular genetic control of sexually dimorphic behaviors. AB - Sex hormones such as estrogen and testosterone are essential for sexually dimorphic behaviors in vertebrates. However, the hormone-activated molecular mechanisms that control the development and function of the underlying neural circuits remain poorly defined. We have identified numerous sexually dimorphic gene expression patterns in the adult mouse hypothalamus and amygdala. We find that adult sex hormones regulate these expression patterns in a sex-specific, regionally restricted manner, suggesting that these genes regulate sex typical behaviors. Indeed, we find that mice with targeted disruptions of each of four of these genes (Brs3, Cckar, Irs4, Sytl4) exhibit extremely specific deficits in sex specific behaviors, with single genes controlling the pattern or extent of male sexual behavior, male aggression, maternal behavior, or female sexual behavior. Taken together, our findings demonstrate that various components of sexually dimorphic behaviors are governed by separable genetic programs. PMID- 22304925 TI - Optimality in the development of intestinal crypts. AB - Intestinal crypts in mammals are comprised of long-lived stem cells and shorter lived progenies. These two populations are maintained in specific proportions during adult life. Here, we investigate the design principles governing the dynamics of these proportions during crypt morphogenesis. Using optimal control theory, we show that a proliferation strategy known as a "bang-bang" control minimizes the time to obtain a mature crypt. This strategy consists of a surge of symmetric stem cell divisions, establishing the entire stem cell pool first, followed by a sharp transition to strictly asymmetric stem cell divisions, producing nonstem cells with a delay. We validate these predictions using lineage tracing and single-molecule fluorescence in situ hybridization of intestinal crypts in infant mice, uncovering small crypts that are entirely composed of Lgr5 labeled stem cells, which become a minority as crypts continue to grow. Our approach can be used to uncover similar design principles in other developmental systems. PMID- 22304926 TI - SnapShot: Insulin signaling pathways. PMID- 22304927 TI - The meanings of DIC diagnostic criteria. PMID- 22304928 TI - Prothrombin complex concentrate (PCC, Octaplex) in patients requiring immediate reversal of vitamin K antagonist anticoagulation. PMID- 22304930 TI - Congenital disorder of glycosylation type Ij (CDG-Ij, DPAGT1-CDG): extending the clinical and molecular spectrum of a rare disease. AB - Congenital disorders of glycosylation (CDG) are caused by enzymatic defects of the formation or processing of lipid-linked oligosaccharides and glycoproteins. Since the majority of proteins is glycosylated, a defect in a singular CDG enzyme leads to a multisytemic disease with secondary malfunction of thousands of proteins. CDG-Ij (DPAGT1-CDG) is caused by a defect of the human DPAGT1 (UDP GlcNAc: Dolichol Phosphate N-Acetylglucosamine-1-Phosphotransferase), catalyzing the first step of N-linked glycosylation. So far the clinical phenotype of only one CDG-Ij patient has been described. The patient showed severe muscular hypotonia, intractable seizures, developmental delay, mental retardation, microcephaly and exotropia. Molecular studies of this patient revealed the heterozygous mutation c.660A>G (Y170C; paternal) in combination with an uncharacterized splicing defect (maternal). Two further mutations, c.890A>T (I297F) and c.162-8G>A as a splicing defect were detected when analyzing DPAGT1 in two affected siblings of a second family. We report two new patients with the novel homozygous mutation, c.341C>G (A114 G), causing a severe clinical phenotype, characterized by hyperexcitability, intractable seizures, bilateral cataracts, progressive microcephaly and muscular hypotonia. Both our patients died within their first year of life. With the discovery of this novel mutation and a detailed clinical description we extend the clinical features of CDG-Ij in order to improve early detection of this disease. PMID- 22304931 TI - Perfluorinated polymer colloids: controlling the size, shape, and surface charge. AB - The first report of perfluorocyclobutyl (PFCB) aryl ether polymer colloids is presented herein. The biphenyl rings were post-functionalized with chlorosulfonic acid modification in the backbone of the perfluoropolymer, thereby changing the zeta potential (zeta) of the colloids across the pH range (2-12). Self-assembly of the colloids was observed by scanning electron microscopy (SEM) on four separate surfaces which led to different morphological changes for each surface; spherical on Al substrate, clover-like on Cr substrate, flower-like on carbon substrate, and "squalloid" on Si substrate. PMID- 22304929 TI - Life with too much polyprenol: polyprenol reductase deficiency. AB - Congenital disorders of glycosylation (CDG) are caused by a dysfunction of glycosylation, an essential step in the manufacturing process of glycoproteins. This paper focuses on a 6-year-old patient with a new type of CDG-I caused by a defect of the steroid 5alpha reductase type 3 gene (SRD5A3). The clinical features were psychomotor retardation, pathological nystagmus, slight muscular hypotonia and microcephaly. SRD5A3 was recently identified encoding the polyprenol reductase, an enzyme catalyzing the final step of the biosynthesis of dolichol, which is required for the assembly of the glycans needed for N glycosylation. Although an early homozygous stop-codon (c.57G>A [W19X]) with no functional protein was found in the patient, about 70% of transferrin (Tf) was correctly glycosylated. Quantification of dolichol and unreduced polyprenol in the patient's fibroblasts demonstrated a high polyprenol/dolichol ratio with normal amounts of dolichol, indicating that high polyprenol levels might compete with dolichol for the initiation of N-glycan assembly but without supporting normal glycosylation and that there must be an alternative pathway for dolichol biosynthesis. PMID- 22304932 TI - Single-step synthesis of layered double hydroxides ultrathin nanosheets. AB - A novel single-step approach was developed to prepare large-scale MgAl-LDHs ultrathin nanosheets. The key point of the successful realization was that we employed a high concentration of H(2)O(2). Oxygen molecules, derived from in situ decomposition of H(2)O(2), were speculated to be the decisive factor leading to complete separation of LDHs layers. The ultrathin nanosheets were characterized by XRD, TEM, AFM, FT-IR, and TG-DSC. The results indicated that the thickness of these nanosheets was about 1.44 nm, which was almost in perfect agreement with the theoretical thickness of two LDHs layers. From the TG-DSC curves, the weight loss of these exfoliated MgAl-LDHs ultrathin nanosheets at 500 degrees C was 18.5%, which was much smaller compared to the 32.3% weight loss of unexfoliated MgAl-LDHs. PMID- 22304933 TI - Novel compaction resistant and ductile nanocomposite nanofibrous microfiltration membranes. AB - Despite promising filtration abilities, low mechanical properties of extraordinary porous electrospun nanofibrous membranes could be a major challenge in their industrial development. In addition, such kind of membranes are usually hydrophobic and non-wettable. To reinforce an electrospun nanofibrous membrane made of polyethersulfone (PES) mechanically and chemically (to improve wettability), zirconia nanoparticles as a novel nanofiller in membrane technology were added to the nanofibers. The compressive and tensile results obtained through nanoindentation and tensile tests, respectively, implied an optimum mechanical properties after incorporation of zirconia nanoparticles. Especially compaction resistance of the electrospun nanofibrous membranes improved significantly as long as no agglomeration of the nanoparticles occurred and the electrospun nanocomposite membranes showed a higher tensile properties without any brittleness i.e. a high ductility. Noteworthy, for the first time the compaction level was quantified through a nanoindentation test. In addition to obtaining a desired mechanical performance, the hydrophobicity declined. Combination of promising properties of optimum mechanical and surface chemical properties led to a considerably high water permeability also retention efficiency of the nanocomposite PES nanofibrous membranes. Such finding implies a longer life span and lower energy consumption for a water filtration process. PMID- 22304934 TI - Alertness network in patients with temporal lobe epilepsy: a fMRI study. AB - Patients with temporal lobe epilepsy (TLE) often suffer from cognitive deficits. However, it remains elusive whether the performance of TLE patients in the attentional networks test (ANT) is impaired. Functional magnetic resonance imaging (fMRI) can accurately reflect the hemodynamics and functional activities in certain regions of the brain. In the current study, we aimed to investigate the characteristics and neural mechanisms of the functions of the alertness network in patients with TLE using the ANT and fMRI. A total of 12 patients with TLE and 8 healthy controls underwent the ANT behavioral tests and subsequent block-design fMRI scanning. The results showed that the response times of the alertness network had no significant difference between the TLE group and the healthy control group. The fMRI data showed that the activation of the cerebellum, right occipital lobe, right frontal and brainstem was significantly weaker in TLE patients than in healthy control. Our data indicate that despite neuropsychological test performance is normal; the alerting network is deficient in the TLE patients. The decreased activation of brain regions of right occipital lobe, cerebellum, right frontal lobe, brain stem and temporal lobe may be the neural basis of altering network impairment in TEL patients. PMID- 22304935 TI - A 21-week open-label clinical trial of pregabalin as adjunctive therapy in partial seizures at multiple centers in Mexico (PREPS Mexico). AB - PURPOSE: To investigate the efficacy of pregabalin in the treatment of refractory partial seizures. METHODS: This was a 21-week, open-label study of pregabalin (150-600 mg/day) as an adjunctive therapy in adults with refractory partial seizures. The study included an 8-week baseline period, a 9-week dose optimization period, and a 12-week treatment-observation period. The primary assessment was mean percentage change in 28-day seizure rate between baseline and the last 12 weeks of treatment. RESULTS: In total, 136 Mexican patients were included in this study (55.9% women; mean age/epilepsy duration, 35.2/22.9 years). The median and mean (95% confidence interval [CI]) 28-day baseline seizure rates were 3.9 and 7.8 (5.4-10.2), respectively. The mean (95% CI) reduction in seizure frequency was 51.2% (43.0-59.3) over the last 12 weeks of treatment, while the median reduction was 57.9%. The percentage of patients with a >= 5 0% or >= 75% reduction in seizure frequency was 63.6% and 48.8%, respectively. The percentage of patients who were seizure-free during the last 4 and 12 weeks of treatment was 40.5% and 20.7%, respectively. The most common adverse events were somnolence (39.7%), dizziness (16.2%), and weight gain (14.0%). CONCLUSION: Pregabalin was well tolerated and associated with significant reductions in seizure frequency. PMID- 22304936 TI - Characterization of Nipah virus from outbreaks in Bangladesh, 2008-2010. AB - Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes fatal encephalitis in humans. The initial outbreak of NiV infection occurred in Malaysia and Singapore in 1998-1999; relatively small, sporadic outbreaks among humans have occurred in Bangladesh since 2001. We characterized the complete genomic sequences of identical NiV isolates from 2 patients in 2008 and partial genomic sequences of throat swab samples from 3 patients in 2010, all from Bangladesh. All sequences from patients in Bangladesh comprised a distinct genetic group. However, the detection of 3 genetically distinct sequences from patients in the districts of Faridpur and Gopalganj indicated multiple co circulating lineages in a localized region over a short time (January-March 2010). Sequence comparisons between the open reading frames of all available NiV genes led us to propose a standardized protocol for genotyping NiV; this protcol provides a simple and accurate way to classify current and future NiV sequences. PMID- 22304938 TI - A few words a propos of neural coding (also thanks alleged and wisdom). Preface. PMID- 22304939 TI - Rapid diagnosis of pandemic (H1N1) 2009 in Cuba. PMID- 22304940 TI - Intrahospital transport of critically ill patients (excluding newborns) recommendations of the Societe de Reanimation de Langue Francaise (SRLF), the Societe Francaise d'Anesthesie et de Reanimation (SFAR), and the Societe Francaise de Medecine d'Urgence (SFMU). AB - Critically ill adult patients often require multiple examinations in the hospital and need transport from one department to another, or even between hospitals. However, to date, no guidelines exist regarding optimum practices for transport of these fragile patients. We present recommendations for intrahospital transport of critically ill patients, excluding newborns, developed by an expert group of the French-Language Society of Intensive Care (Societe de Reanimation de Langue Francaise (SRLF), the Societe Francaise d'Anesthesie et de Reanimation (SFAR), and the Societe Francaise de Medecine d'Urgence (SFMU). The recommendations cover five fields of application: epidemiology of adverse events; equipment, monitoring, and maintenance; preparation of patient before transport; human resources and training for caregivers involved in transport processes; and guidelines for planning, structure, and traceability of transport processes. PMID- 22304941 TI - Increased hyaluronan levels and decreased dendritic cell activation are associated with tumor invasion in murine lymphoma cell lines. AB - Hyaluronan (HA), a component of the extracellular matrix surrounding tumors, modulates tumor progression and the immune response. Dendritic cells (DC) may tolerize or stimulate immunity against cancer. In this report, we study the association between tumor progression, HA levels and DC activation in a lymphoma model. Mice injected with the cells with highest invasive capacity (LBR-) presented increased HA in serum and lymph nodes, and decreased DC activation in infiltrated lymph nodes and liver. These findings could be related to lack of an effective antitumor immune response and suggest that serum HA levels could have a prognostic value in hematological malignancies. PMID- 22304942 TI - C5a receptor is cleaved by metalloproteases induced by sphingomyelinase D from Loxosceles spider venom. AB - Neutrophils are involved in numerous pathologies and are considered to be major contributors to the establishment of cutaneous loxoscelism after envenomation by the Loxosceles spider. Neutrophils are attracted to the site of envenomation by locally generated C5a and contribute to the tissue destruction. We have investigated the effects of this spider venom on the receptor for C5a: C5aR/CD88, a seven transmembrane G-protein coupled receptor. We show here that the Loxosceles venom induces the cleavage of the C5aR at two sites, resulting in the release of the extracellular N-terminus, while retaining part of the transmembrane regions. Using specific inhibitors, it was shown that the cleavage was induced by activation of an endogenous metalloprotease of the adamalysin (ADAM) family, which was activated by the sphingomyelinase D in the venom. Although it resulted in the near complete loss of the N-terminus, C5a was still able to induce a small increase in intracellular calcium and increase secretion of IL-8. The cleavage of the C5aR may well be a protective response after envenomation, rather than contributing to the pathology of Loxosceles envenomation and may represent a general mechanism for how the body protects itself against excess C5a generation in pathological circumstances such as sepsis. PMID- 22304943 TI - Coherency strain and the kinetics of phase separation in LiFePO4 nanoparticles. AB - A theoretical investigation of the effects of elastic coherency strain on the thermodynamics, kinetics, and morphology of intercalation in single LiFePO(4) nanoparticles yields new insights into this important battery material. Anisotropic elastic stiffness and misfit strains lead to the unexpected prediction that low-energy phase boundaries occur along {101} planes, while conflicting reports of phase boundary orientations are resolved by a partial loss of coherency in the [001] direction. Elastic relaxation near surfaces leads to the formation of a striped morphology with a characteristic length scale predicted by the model, yielding an estimate of the interfacial energy. The effects of coherency strain on solubility and galvanostatic discharge are studied with a reaction-limited phase-field model that quantitatively captures the influence of misfit strain, particle size, and temperature on solubility seen in experiments. Coherency strain strongly suppresses phase separation during discharge, which enhances rate capability and extends cycle life. The effects of elevated temperature and the feasibility of nucleation are considered in the context of multiparticle cathodes. PMID- 22304944 TI - A meta-analysis of the effects of interleukin-6 -174 G>C genetic polymorphism on acute graft-versus-host disease susceptibility. AB - BACKGROUND: The interleukin-6 (IL-6) -174 G>C genetic polymorphism has been implicated to play an important role in acute graft-versus-host disease (aGVHD). However, previous studies have yielded inconclusive results as to its role in patient susceptibility to aGVHD, and no study to date has systematically analyzed this polymorphism. OBJECTIVE: A meta-analysis of the published evidence was conducted to estimate the true effect of the IL-6 -174 G>C genetic polymorphism in allogeneic hematopoietic stem cell transplantation (alloHSCT) patients and donors on the risk of aGVHD. METHODS: Seven cohort studies, comprising 1287 recipient and donor pairs, were included after eliminating 62 studies that met the following exclusion criteria: irrelevant studies other than cohort studies, without sufficient data, and with overlapping data. Although interstudy heterogeneity existed, most studies were conducted in the United States or Europe and included adult patients with hematologic disease who received alloHSCT from human leukocyte antigen-matched or identical sibling donors. The effect of the polymorphism on aGVHD risk (grades I-IV, II-IV, and III-IV) was estimated from odds ratios with 95% confidence intervals for the dominant genetic model and recessive model, respectively. RESULTS: Patients who received grafts from donors with the IL-6 G allele experienced more frequent grade I-IV aGVHD (odds ratio = 3.304 [95% confidence interval, 1.456-7.494]) and grade II-IV aGVHD (odds ratio = 1.738 [95% CI, 1.006 - 3.001]). CONCLUSIONS: To our knowledge, this is the first meta-analysis to evaluate the relation between a non-human leukocyte antigen gene polymorphism and the risk of aGVHD. Our meta-analysis combined the results of several studies and demonstrated that the donor IL-6 G allele is associated with an increased risk of grades I-IV and II-IV aGVHD. PMID- 22304945 TI - Technical advances in cardiac CT. AB - Cardiac computed tomography (CT) and its main clinical application, coronary CT angiography, have made major progress during the past years. Advances were driven by progress in CT hardware technology and CT image reconstruction and processing software. Technical innovations have successfully been used to lower the radiation exposure of coronary CT angiography and to improve image quality, especially in challenging situations, such as individuals with high heart rates or severe calcification. Some of the most important recent contributions have been the development of area detectors, dual-source CT, and the introduction of iterative reconstruction algorithms. PMID- 22304946 TI - Minimizing radiation dose for coronary CT angiography. AB - Coronary CT angiography is a rapidly growing technique that offers distinct advantages over traditional imaging techniques. However, because of rapid growth of this technique, radiation dose safety has been placed under the spotlight. There are several main determinants of total radiation dose, and these are outlined in this review. Integration of these dose-saving techniques will go a long way in maintaining diagnostic image quality and improving patient safety. PMID- 22304947 TI - Coronary artery calcification and coronary atherosclerotic disease. AB - The presence of coronary artery calcium is closely associated with the presence of atherosclerotic lesions in the coronary vasculature. Detection of coronary calcium by imaging techniques has evolved over the last few decades and has become especially more sophisticated with advanced imaging technology. Whereas the status of coronary artery calcium as a marker of increased cardiovascular risk is well established, the indication for testing continues to be a topic of debate. PMID- 22304948 TI - Coronary artery calcium testing: dos and don'ts. AB - Measurement of traditional risk factors remains the foundation of current clinical practice guidelines when screening for coronary heart disease (CHD) risk. However, many adults who experience CHD events are not identified as higher risk based on their traditional risk factors. Observational data show that the coronary artery calcium (CAC) score improves risk prediction, even after taking into account traditional risk factors. The authors have outlined several principles of CAC testing into a list of dos and don'ts to help maximize its potential benefit while minimizing potential harm. PMID- 22304949 TI - Identifying and redefining stenosis by CT angiography. AB - Coronary computed tomographic angiography (CCTA) has emerged as a novel noninvasive method for the evaluation of not only coronary artery stenosis but also arterial wall and plaque features. Recent developments in CCTA technology enable the simultaneous assessment of coronary stenosis, atherosclerotic plaque characteristics, physiologic significance of lesion-specific ischemia, and cardiac function. Through these studies, the prognostic significance of individual coronary lesions and ventricular function can be determined and used to direct therapy. Future studies are needed to establish the totality of coronary artery plaque measures that improve clinical utility. PMID- 22304950 TI - Evaluation of plaque morphology by coronary CT angiography. AB - Coronary computed tomographic angiography (CTA) is a promising noninvasive tool that allows the visualization of plaque morphology. Plaques characterized by positive remodeling, low attenuation, and napkin ring circular enhancement on contrast-enhanced coronary CTA have been regarded as rupture-prone vulnerable plaques, which account for about 60% of all vulnerable lesions and may be precursors of plaque rupture. In this article, the authors discuss the various features related to plaque morphology that are essential to detect vulnerable plaques while performing coronary CTA. PMID- 22304951 TI - Prognostic value of coronary CT angiography. AB - Coronary computed tomography angiography (CTA) is a highly accurate noninvasive test that is increasingly used in symptomatic patients primarily for the diagnosis of coronary artery disease (CAD). Beyond its proven accuracy, data have now clearly demonstrated the incremental prognostic information available from coronary CTA related to the presence, extent, and severity of obstructive and nonobstructive CAD across a variety of clinical settings and patient populations. Current evidence supports the use of coronary CTA not only for the diagnosis of CAD in appropriately selected symptomatic patients but also to further refine their cardiovascular risk assessment following testing. PMID- 22304952 TI - Subtraction coronary CT angiography for calcified lesions. AB - One of the main problems in coronary angiography using 64-row computed tomography (CT) is that the presence of severe calcification interferes with the assessment of lesions, which reduces diagnostic accuracy and may even make assessment of some coronary artery segments impossible. With 320-row CT, it is possible to avoid this problem by performing subtraction coronary CT, which fully exploits the performance capabilities of the CT system. However, subtraction coronary CT has several limitations. When these limitations have been overcome, this technique is expected to become a useful method for assessing patients with severe calcification and evaluating coronary artery stents. PMID- 22304953 TI - CT detection of pulmonary embolism and aortic dissection. AB - Triage of patients with acute, potentially life-threatening chest pain is one of the most daunting challenges currently facing emergency department physicians. Acute aortic syndrome and pulmonary embolism are two potentially underlying causes. For both, computed tomography has become the de facto clinical reference standard for diagnosis. This article discusses state-of-the-art computed tomography for the detection of these disorders, including recent advances and future perspectives. PMID- 22304954 TI - Cardiac CT in the emergency department. AB - Current triage strategies are not effective in correctly identifying patients suffering from acute coronary syndrome (ACS). The diagnostic workup of patients presenting with acute chest pain continues to represent a major challenge for emergency department (ED) personnel. This statement holds especially true for patients with a low to intermediate likelihood for ACS. Taking current concepts for the diagnosis and management of patients presenting with acute chest pain to the ED into account, this article discusses the evidence and potential role of coronary computed tomography angiography to improve management of patients with possible ACS. PMID- 22304955 TI - Myocardial perfusion by CT versus hybrid imaging. AB - Coronary computed tomography angiography (CTA) is a reliable diagnostic test for the anatomic diagnosis of obstructive coronary artery disease (CAD). Although coronary CTA shows high sensitivity and negative predictive value for detecting stenosis greater than or equal to 50% diameter, it is limited in its ability to diagnose myocardial ischemia. Advances in computed tomography (CT) technology alone and technology that hybridizes CT with single-photon emission CT and positron emission tomography allow for the combined anatomic and physiologic diagnosis of CAD. This article summarizes these combined technologies, emphasizing the merits and limitations of each technology and their clinical implications. PMID- 22304956 TI - MDCT to guide transcatheter aortic valve replacement and mitral valve repair. AB - Percutaneous management of valvular heart disease is becoming a reality, with multicenter trials supporting minimally invasive procedures for both aortic and mitral valve disease. Historically, the treatment of choice has been aortic valve replacement with conventional surgery for patients with severe aortic stenosis, as the prognosis of untreated patients is poor, particularly if the patient is symptomatic. Transcatheter aortic valve replacement is now available as a minimally invasive option to treat select high-risk patients with severe aortic stenosis. At present more than 30,000 procedures have been performed worldwide, mostly confined to patients at high surgical risk. The short- and medium-term outcomes have been promising. PMID- 22304959 TI - Early detection of placental inflammation by MRI enabling protection by clinically relevant IL-1Ra administration. AB - OBJECTIVE: We studied whether magnetic resonance imaging (MRI) could be used to detect placental inflammation before the detection of irreversible tissue damage. Next, we tested whether this early detection would enable the administration of treatment (ie, interleukin-1 receptor antagonist [IL-1Ra]) in a realistic clinical time after diagnosis. STUDY DESIGN: Pregnant rats were injected intraperitoneally with lipopolysaccharide with/without delayed IL-1Ra. MRI was performed at different time after the injection, and placentas were collected for comparison. Placental inflammation was assessed by determination of the levels of inflammatory cytokines. RESULTS: Placental inflammation was detected by MRI as early as 3 hours after maternal administration of lipopolysaccharide, concomitantly to IL-1beta up-regulation. This was observed before any tissue damage, which appeared only at 24 hours after the administration of lipopolysaccharide. Delayed IL-1Ra administration (after MRI diagnosis) protected the placenta, as seen by the preserved tissue integrity and limited macrophages infiltration in the placental parenchyma. CONCLUSION: These findings established a noninvasive diagnostic method for early in utero detection of placental inflammation that would allow the administration of placentoprotective intervention within a clinically relevant delay after diagnosis. PMID- 22304960 TI - Stability of vocational interests after recent spinal cord injury: comparisons related to sex and race. AB - OBJECTIVE: To identify the stability of vocational interests first assessed during inpatient rehabilitation for spinal cord injury and again an average of 834.9 days postinjury to determine the extent to which stability of interest varies as a function of race and sex. DESIGN: Longitudinal. SETTING: Data were collected at a specialty hospital. PARTICIPANTS: At enrollment, participants were a minimum of 16 years of age, were currently hospitalized for inpatient rehabilitation, were less than 6 months postinjury, had residual impairment after traumatic spinal cord injury, and were either white or black, and non-Hispanic. Participants (N=304) were assessed an average +/- SD of 50+/-26.6 days after injury and again an average +/- SD of 834.9+/-192.7 days postinjury (averaged 785.1 d between assessments). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The Strong Interest Inventory, a 317-item vocational interests measure. RESULTS: A repeated-measures general linear model was used with 4 groups based on a combination of race and sex. Significant cohort by time interactions were observed on 4 general occupational themes (investigative, artistic, enterprising, and conventional). In nearly all cases, black women showed decreases in average interest scores compared with the other groups. There was a clear pattern of change in the direction of greater homogeneity of interests over time as measured by the range of theme scores between cohorts based on sex and race. Although changes in mean interest profiles varied as a function of sex and race, less consistent differences were observed when stability coefficients were the measure of change. CONCLUSIONS: The direction and degree of change in mean scores for vocational interests was related to sex and race. With the exception of black women, vocational interests increased from baseline to follow-up. PMID- 22304961 TI - Degradable segmented polyurethane elastomers for bone tissue engineering: effect of polycaprolactone content. AB - Segmented polyurethanes (PURs), consisting of degradable poly(a-hydroxy ester) soft segments and aminoacid-derived chain extenders, are biocompatible elastomers with tunable mechanical and degradative properties suitable for a variety of tissue-engineering applications. In this study, a family of linear PURs synthesized from poly(epsilon-caprolactone) (PCL) diol, 1,4-diisocyanobutane and tyramine with theoretical PCL contents of 65-80 wt% were processed into porous foam scaffolds and evaluated for their ability to support osteoblastic differentiation in vitro. Differential scanning calorimetry and mechanical testing of the foams indicated increasing polymer crystallinity and compressive modulus with increasing PCL content. Next, bone marrow stromal cells (BMSCs) were seeded into PUR scaffolds, as well as poly(lactic-co-glycolic acid) (PLGA) scaffolds, and maintained under osteogenic conditions for 14 and 21 days. Analysis of cell number indicated a systematic decrease in cell density with increasing PUR stiffness at both 14 and 21 days in culture. However, at these same time points the relative mRNA expression for the bone-specific proteins osteocalcin and the growth factors bone morphogenetic protein-2 and vascular endothelial growth factor gene expression were similar among the PURs. Finally, prostaglandin E2 production, alkaline phosphatase activity and osteopontin mRNA expression were highly elevated on the most-crystalline PUR scaffold as compared to the PLGA and PUR scaffolds. These results suggest that both the modulus and crystallinity of the PUR scaffolds influence cell proliferation and the expression of osteoblastic proteins. PMID- 22304962 TI - Nanostructured morphology of a random P(DLLA-co-CL) copolymer. AB - The random architecture of a commercial copolymer of poly(DL-lactic acid) and poly(epsilon-caprolactone), poly(DL-lactide-co-caprolactone), has been characterized by chemical structure analysis from hydrogen-1 nuclear magnetic resonance results. Moreover, spherical nanodomains have been detected in the thin films of this copolymer obtained after solvent evaporation. These nanodomains studied by atomic force microscopy and transmission elecron microscopy grow progressively under annealing until they collapse and form a homogenous disordered structure. This is the first time that the nanostructure of random poly(DL-lactic acid)/poly-(epsilon-caprolactone) copolymers is revealed, representing one of few experimental evidences on the possible nanostructuration of random copolymers. PMID- 22304963 TI - Measurement of mass attenuation coefficients of Rhizophora spp. binderless particleboards in the 16.59-25.26 keV photon energy range and their density profile using x-ray computed tomography. AB - The mass attenuation coefficients of Rhizophora spp. binderless particleboard with four different particle sizes (samples A, B, C and D) and natural raw Rhizophora spp. wood (sample E) were determined using single-beam photon transmission in the energy range between 16.59 and 25.26 keV. This was done by determining the attenuation of K(alpha1) X-ray fluorescent (XRF) photons from niobium, molybdenum, palladium, silver and tin targets. The results were compared with theoretical values of young-age breast (Breast 1) and water calculated using a XCOM computer program. It was found that the mass attenuation coefficient of Rhizophora spp. binderless particleboards to be close to the calculated XCOM values in water than natural Rhizophora spp. wood. Computed tomography (CT) scans were then used to determine the density profile of the samples. The CT scan results showed that the Rhizophora spp. binderless particleboard has uniform density compared to natural Rhizophora spp. wood. In general, the differences in the variability of the profile density decrease as the particle size of the pellet samples decreases. PMID- 22304964 TI - Thin CaSO4:Dy thermoluminescent dosimeters for calibration of 90Sr+90Y applicators. AB - Clinical applicators are used in brachytherapy to treat superficial lesions of skin and eye. They should be periodically calibrated according to quality control programs and international recommendations. Thin CaSO(4):Dy thermoluminescent dosimeters were used to calibrate various applicators with a dermatological applicator as a reference. The obtained absorbed dose rates were compared with those quoted in their calibration certificates. Depth-dose curves were constructed for all the applicators. A mail dosimetry system was developed for calibration of clinical applicators. PMID- 22304965 TI - Why is high-risk drinking more prevalent among men than women? Evidence from South Korea. AB - BACKGROUND: It is important to identify and quantify the factors that affect gender differences in high-risk drinking (HRD), from both an academic and a policy perspective. However, little is currently known about them. This study examines these factors and estimates the percentage contribution each makes to gender differences in HRD. METHODS: This study analyzed information on 23,587 adults obtained from the Korea National Health and Nutrition Surveys of 1998, 2001, and 2005. It found that the prevalence of HRD was about 5 times higher among men (0.37) than women (0.08). Using a decomposition approach extended from the Oaxaca-Blinder method, we decomposed the gender difference in HRD to an "overall composition effect" (contributions due to gender differences in the distribution of observed socio-economic characteristics), and an "overall HRD tendency effect" (contributions due to gender differences in tendencies in HRD for individuals who share socio-economic characteristics). RESULTS: The HRD tendency effect accounted for 96% of the gender difference in HRD in South Korea, whereas gender differences in observed socio-economic characteristics explained just 4% of the difference. Notably, the gender-specific HRD-tendency effect accounts for 90% of the gender difference in HRD. CONCLUSION: We came to a finding that gender-specific HRD tendency is the greatest contributor to gender differences in HRD. Therefore, to effective reduce HRD, it will be necessary to understand gender differences in socioeconomic characteristics between men and women but also take notice of such differences in sociocultural settings as they experience. And it will be also required to prepare any gender-differentiated intervention strategy for men and women. PMID- 22304966 TI - From extant to extinct: locomotor ontogeny and the evolution of avian flight. AB - Evolutionary transformations are recorded by fossils with transitional morphologies, and are key to understanding the history of life. Reconstructing these transformations requires interpreting functional attributes of extinct forms by exploring how similar features function in extant organisms. However, extinct-extant comparisons are often difficult, because extant adult forms frequently differ substantially from fossil material. Here, we illustrate how postnatal developmental transitions in extant birds can provide rich and novel insights into evolutionary transformations in theropod dinosaurs. Although juveniles have not been a focus of extinct-extant comparisons, developing juveniles in many groups transition through intermediate morphological, functional and behavioral stages that anatomically and conceptually parallel evolutionary transformations. Exploring developmental transitions may thus disclose observable, ecologically relevant answers to long puzzling evolutionary questions. PMID- 22304967 TI - XIAP monoubiquitylates Groucho/TLE to promote canonical Wnt signaling. AB - A key event in Wnt signaling is conversion of TCF/Lef from a transcriptional repressor to an activator, yet how this switch occurs is not well understood. Here, we report an unanticipated role for X-linked inhibitor of apoptosis (XIAP) in regulating this critical Wnt signaling event that is independent of its antiapoptotic function. We identified DIAP1 as a positive regulator of Wingless signaling in a Drosophila S2 cell-based RNAi screen. XIAP, its vertebrate homolog, is similarly required for Wnt signaling in cultured mammalian cells and in Xenopus embryos, indicating evolutionary conservation of function. Upon Wnt pathway activation, XIAP is recruited to TCF/Lef where it monoubiquitylates Groucho (Gro)/TLE. This modification decreases affinity of Gro/TLE for TCF/Lef. Our data reveal a transcriptional switch involving XIAP-mediated ubiquitylation of Gro/TLE that facilitates its removal from TCF/Lef, thus allowing beta-catenin TCF/Lef complex assembly and initiation of a Wnt-specific transcriptional program. PMID- 22304968 TI - Use of complementary and alternative medicine in a large sample of anxiety patients. AB - OBJECTIVE: To examine a large sample of patients with anxiety and the association between types of complementary and alternative treatments that were used, demographic variables, diagnostic categories, and treatment outcomes. METHOD: Cross-sectional and longitudinal survey during the Coordinated Anxiety Learning and Management (CALM) study that assessed this intervention against the Usual Care in a sample of patients with anxiety recruited from primary care. Interviewer-administered questionnaires via a centralized telephone survey by blinded assessment raters. The interviews were done at baseline, 6, 12, and 18 months of the study. A total of 1004 adults ages 18-75 who met DSM-IV criteria for Generalized Anxiety Disorder (GAD), Panic Disorder, Social Anxiety Disorder, or Post-Traumatic Stress Disorder. We assessed medication/herbal use, the use of any alternative therapies, and combined Complementary and Alternative Medicine (CAM) use. RESULTS: We found an extensive (43%) use of a variety of CAM treatments that is consistent with previous study results in populations with anxiety. Only a few significant demographic or interventional characteristics of CAM users were found. Users most often had a diagnosis of GAD, were older, more educated, and had two or more chronic medical conditions. CAM users who had a 50% or more drop in anxiety scores over 18 months were less likely to report continued use of alternative therapies. CONCLUSIONS: The study confirms the importance of awareness of CAM use in this population for possible interference with traditional first-line treatments of these disorders, but also for finding the best integrative use for patients who require multiple treatment modalities. PMID- 22304971 TI - Complex phytohormone responses during the cold acclimation of two wheat cultivars differing in cold tolerance, winter Samanta and spring Sandra. AB - Hormonal changes accompanying the cold stress (4 degrees C) response that are related to the level of frost tolerance (FT; measured as LT50) and the content of the most abundant dehydrin, WCS120, were compared in the leaves and crowns of the winter wheat (Triticum aestivum L.) cv. Samanta and the spring wheat cv. Sandra. The characteristic feature of the alarm phase (1 day) response was a rapid elevation of abscisic acid (ABA) and an increase of protective proteins (dehydrin WCS120). This response was faster and stronger in winter wheat, where it coincided with the downregulation of bioactive cytokinins and auxin as well as enhanced deactivation of gibberellins, indicating rapid suppression of growth. Next, the ethylene precursor aminocyclopropane carboxylic acid was quickly upregulated. After 3-7 days of cold exposure, plant adaptation to the low temperature was correlated with a decrease in ABA and elevation of growth promoting hormones (cytokinins, auxin and gibberellins). The content of other stress hormones, i.e., salicylic acid and jasmonic acid, also began to increase. After prolonged cold exposure (21 days), a resistance phase occurred. The winter cultivar exhibited substantially enhanced FT, which was associated with a decline in bioactive cytokinins and auxin. The inability of the spring cultivar to further increase its FT was correlated with maintenance of a relatively higher cytokinin and auxin content, which was achieved during the acclimation period. PMID- 22304972 TI - Unsuspected dengue and acute febrile illness in rural and semi-urban southern Sri Lanka. AB - Dengue virus (DENV), a globally emerging cause of undifferentiated fever, has been documented in the heavily urbanized western coast of Sri Lanka since the 1960s. New areas of Sri Lanka are now being affected, and the reported number and severity of cases have increased. To study emerging DENV in southern Sri Lanka, we obtained epidemiologic and clinical data and acute- and convalescent-phase serum samples from patients >2 years old with febrile illness. We tested paired serum samples for DENV IgG and IgM and serotyped virus by using isolation and reverse transcription PCR. We identified acute DENV infection (serotypes 2, 3, and 4) in 54 (6.3%) of 859 patients. Only 14% of patients had clinically suspected dengue; however, 54% had serologically confirmed acute or past DENV infection. DENV is a major and largely unrecognized cause of fever in southern Sri Lanka, especially in young adults. PMID- 22304973 TI - Adult-onset muscular dystrophy in a cat associated with a presumptive alteration in trafficking of caveolin-3. AB - A 10-year-old neutered female domestic longhaired cat was referred for evaluation of forelimb weakness and lameness. There was hypertrophy and firmness of the musculature with no neurological deficits. Moderate increase of creatine kinase activity was present. Muscle biopsy showed rounded atrophic and hypertrophic fibres, an increased number of centrally located myofibre nuclei, scattered rimmed vacuoles and mild perimysial and endomysial fibrosis. Myofibre necrosis with phagocytosis was present in the gluteal muscle. Immunohistochemistry revealed absence of sarcolemmal caveolin-3 in almost all muscle fibres and sarcoplasmic accumulation of the protein in approximately 30% of myofibres. Normal expression of caveolin-3 was detected by immunoblotting, so protein mislocalization in the sarcoplasm due to aberrant trafficking towards the sarcolemma was suspected. This case represents the first example of muscular dystrophy due to a caveolinopathy in animals. PMID- 22304974 TI - Kinetics of the inflammatory response in subcutaneous cysticercosis induced in mice by Taenia crassiceps. AB - The larval stage of Taenia crassiceps has been used to study human cysticercosis as these larvae have antigenic similarity to the cysticerci of Taenia solium. The aim of this study was to evaluate the histopathological and immunological changes that followed the inoculation of T. crassiceps cysticerci into the subcutaneous tissue of C57BL/6 mice. Microscopically, granulomas formed of neutrophils and macrophages developed at the sites of inoculation. The serum concentration of the cytokine interferon (IFN)-gamma increased throughout the course of infection, while the serum concentration of interleukin-4 increased during the period of transition from the initial phase (7-30 days postinoculation [dpi]) to the late phase (60-90 dpi) of infection. Destruction of the parasite therefore appears to be associated with an increase in IFN-gamma, suggesting that a type 1 immune response is important in the control of the parasite. PMID- 22304975 TI - Orbital embryonal rhabdomyosarcoma with metastasis in a young dog. AB - A 2-year-old male Welsh corgi dog was brought to an animal hospital because of left upper eyelid enlargement with lachrymal gland protrusion. The lachrymal and orbital cavity mass was removed surgically. Microscopically, the orbital mass consisted of a mixture of large rhabdomyoblastic and small round tumour cells. Immunohistochemically, the rhabdomyoblastic cells expressed desmin and myoglobin and the small round cells expressed desmin, myogenin and MyoD1. A diagnosis of embryonal rhabdomyosarcoma (ERS) was made. One month later, multiple masses throughout the body were identified, in particular around the cervical region. One of these lesions was sampled and diagnosed as metastatic ERS. The dog died 84 days after the time of first admission. PMID- 22304976 TI - Evaluating sex and gender competencies in the medical curriculum: a case study. AB - BACKGROUND: Sex and gender differences exist in the manifestation and prevalence of many conditions and diseases. Yet many clinician training programs neglect to integrate this information across their curricula. OBJECTIVE: This study aimed to measure the sex and gender medical knowledge of medical students enrolled in a program without an explicit directive to integrate sex and gender differences across a block system of core subjects. METHODS: A forced-choice instrument consisting of 35 multiple-choice and true or false questions was adapted from an evaluation tool used in the European Curriculum in Gender Medicine held at Charite Hospital, Berlin, in September 2010. RESULTS: Fourth-year (response rate 93%) and second-year (response rate 70%) students enrolled in Mayo Medical School completed the instrument. More than 50% of students in both classes indicated that topics related to sex and gender were covered in gynecology, cardiology, and pediatrics, and <20% of students indicated inclusion of such topics in nephrology, neurology, and orthopedics. More than twice as many second-year students indicated that topics dealing with sex and gender were included in immunology course material compared with fourth-year students. A consensus of written comments indicated that concepts of sex and gender-based medicine need to be embedded into existing curriculum, with an emphasis on clinically relevant information. CONCLUSIONS: Although this study represents only one medical school in the United States, information regarding sex and gender aspects of medicine is not consistently included in this curriculum without an explicit directive. These results can provide guidance for curriculum improvement to train future physicians. PMID- 22304977 TI - Comparison of adaptive statistical iterative and filtered back projection reconstruction techniques in brain CT. AB - PURPOSE: To compare image quality and visualization of normal structures and lesions in brain computed tomography (CT) with adaptive statistical iterative reconstruction (ASIR) and filtered back projection (FBP) reconstruction techniques in different X-ray tube current-time products. MATERIALS AND METHODS: In this IRB-approved prospective study, forty patients (nineteen men, twenty-one women; mean age 69.5 +/- 11.2 years) received brain scan at different tube current-time products (300 and 200 mAs) in 64-section multi-detector CT (GE, Discovery CT750 HD). Images were reconstructed with FBP and four levels of ASIR FBP blending. Two radiologists (please note that our hospital is renowned for its geriatric medicine department, and these two radiologists are more experienced in chronic cerebral vascular disease than in neoplastic disease, so this research did not contain cerebral tumors but as a discussion) assessed all the reconstructed images for visibility of normal structures, lesion conspicuity, image contrast and diagnostic confidence in a blinded and randomized manner. Volume CT dose index (CTDI(vol)) and dose-length product (DLP) were recorded. All the data were analyzed by using SPSS 13.0 statistical analysis software. RESULTS: There was no statistically significant difference between the image qualities at 200 mAs with 50% ASIR blending technique and 300 mAs with FBP technique (p>.05). While between the image qualities at 200 mAs with FBP and 300 mAs with FBP technique a statistically significant difference (p<.05) was found. CONCLUSION: ASIR provided same image quality and diagnostic ability in brain imaging with greater than 30% dose reduction compared with FBP reconstruction technique. PMID- 22304978 TI - Detection of hepatic metastases: gadolinium-enhanced MR imaging versus superparamagnetic iron oxide-enhanced MR imaging versus diffusion-weighted imaging. PMID- 22304979 TI - In an animal model nephrogenic systemic fibrosis cannot be induced by intraperitoneal injection of high-dose gadolinium based contrast agents. AB - AIM AND OBJECTIVE: Nephrogenic systemic fibrosis (NSF) has been reported in humans to be most likely induced by gadolinium based contrast agents (GBCA), namely by gadodiamide, gadopentetate dimeglumine, and gadoversetamide, rarely by other GBCA. The pathogenesis of NSF remains unclear; different hypotheses are under discussion. The objective of the study is to assess if in the animal model human-like NSF changes can be induced by high-dose, intraperitoneal GBCA injections over four weeks. MATERIALS AND METHODS: After approval by the institutional animal ethics committee, six rats each were randomly assigned to groups, and treated with seven different GBCA. Intraperitoneal (IP) injections - proven in the animal model to be effective - were chosen to prolong the animals' exposure to the respective GBCA. GBCA doses of previous intravenous (IV) animal studies were applied. After five weeks all rats were sacrificed. Sham controls were treated with IP saline injections, employing the same regimen. RESULTS: No findings comparable with human NSF were observed in all animals after IP treatment with all seven GBCA at daily doses of 2.5 and 5.0 mmol/kg body weight (BW). No histopathological abnormalities of all examined organs were noted. Weight loss was stated in weeks three and four with GBCA injections at doses of 5.0 mmol/kg BW, but rats regained weight after cessation of GBCA treatment. CONCLUSIONS: NSF-comparable pathological findings could not be induced by high dose intraperitoneal injection of seven GBCA. PMID- 22304980 TI - Feasibility of an automatic computer-assisted algorithm for the detection of significant coronary artery disease in patients presenting with acute chest pain. AB - Automatic computer-assisted detection (auto-CAD) of significant coronary artery disease (CAD) in coronary computed tomography angiography (cCTA) has been shown to have relatively high accuracy. However, to date, scarce data are available regarding the performance of auto-CAD in the setting of acute chest pain. This study sought to demonstrate the feasibility of an auto-CAD algorithm for cCTA in patients presenting with acute chest pain. We retrospectively investigated 398 consecutive patients (229 male, mean age 50+/-21 years) who had acute chest pain and underwent cCTA between Apr 2007 and Jan 2011 in the emergency department (ED). All cCTA data were analyzed using an auto-CAD algorithm for the detection of >50% CAD on cCTA. The accuracy of auto-CAD was compared with the formal radiology report. In 380 of 398 patients (18 were excluded due to failure of data processing), per-patient analysis of auto-CAD revealed the following: sensitivity 94%, specificity 63%, positive predictive value (PPV) 76%, and negative predictive value (NPV) 89%. After the exclusion of 37 cases that were interpreted as invalid by the auto-CAD algorithm, the NPV was further increased up to 97%, considering the false-negative cases in the formal radiology report, and was confirmed by subsequent invasive angiogram during the index visit. We successfully demonstrated the high accuracy of an auto-CAD algorithm, compared with the formal radiology report, for the detection of >50% CAD on cCTA in the setting of acute chest pain. The auto-CAD algorithm can be used to facilitate the decision-making process in the ED. PMID- 22304981 TI - Radiation exposure to operating staff during rotational flat-panel angiography and C-arm cone beam computed tomography (CT) applications. AB - PURPOSE: To evaluate the radiation exposure for operating personnel associated with rotational flat-panel angiography and C-arm cone beam CT. MATERIALS AND METHODS: Using a dedicated angiography-suite, 2D and 3D examinations of the liver were performed on a phantom to generate scattered radiation. Exposure was measured with a dosimeter at predefined heights (eye, thyroid, breast, gonads and knee) at the physician's location. Analysis included 3D procedures with a field of view (FOV) of 24 cm * 18 cm (8s/rotation, 20s/rotation and 5s/2 rotations), and 47 cm*18 cm (16s/2 rotations) and standard 2D angiography (10s, FOV 24 cm*18 cm). RESULTS: Measurements showed the highest radiation dose at the eye and thyroid level. In comparison to 2D-DSA (3.9 MUSv eye-exposure), the 3D procedures caused an increased radiation exposure both in standard FOV (8s/rotation: 28.0 MUSv, 20s/rotation: 79.3 MUSv, 5s/2 rotations: 32.5 MUSv) and large FOV (37.6 MUSv). Proportional distributions were measured for the residual heights. With the use of lead glass, irradiation of the eye lens was reduced to 0.2 MUSv (2D DSA) and 10.6 MUSv (3D technique with 20s/rotation). CONCLUSION: Rotational flat panel angiography and C-arm cone beam applications significantly increase radiation exposure to the attending operator in comparison to 2D angiography. Our study indicates that the physician should wear protective devices and leave the examination room when performing 3D examinations. PMID- 22304982 TI - T-staging of gastric cancer of air-filling multidetector-row CT: comparison with hydro-multidetector-row CT. AB - PURPOSE: The purpose of this study was to evaluate the accuracy of T-staging of gastric cancer by air-filling multidetector-row CT (air-MDCT) compared with water filling MDCT (hydro-MDCT). MATERIALS AND METHODS: One hundred fifteen patients with histologically diagnosed gastric cancer were included in this study. Fifty eight patients underwent air-MDCT, and the remaining 57 had hydro-MDCT using a 64 channel scanner. Based on the volumetric data of contrast-enhanced MDCT obtained about 75 s after intravenously injecting 525 mg iodine per kilogram patients weight (525 mgI/kg) nonionic contrast material at the rate of 2 ml/s, oblique coronal and oblique sagittal multi-planar reformatted images perpendicular to the stomach wall, including the tumor, were reconstructed on a workstation. Mural invasion of gastric cancer into the gastric wall, as visualized by CT, was classified according to the TNM classification, and the results of T-staging by MDCT were compared with those by pathologic analysis after surgery. RESULTS: Correct assessment of T-staging by air-CT was achieved in 48 of 58 patients (83%), and that by hydro-MDCT was 49 of 57 patients (86%). The sensitivity, specificity, and accuracy of the technique in determining the invasion of serosa were 88%, 93%, and 91% for air-CT and 83%, 95%, and 91% for hydro-CT. There were no significant differences between hydro-MDCT and air-MDCT in sensitivity (P=0.73), specificity (P=0.71) and accuracy (P=0.98). CONCLUSION: Air-MDCT is a very valuable tool in T-staging of gastric cancer as well as hydro-MDCT. PMID- 22304983 TI - Hand, foot, and mouth disease caused by coxsackievirus A6, Japan, 2011. PMID- 22304984 TI - Cortical thickness, neuron density and size in the inferior parietal lobe in schizophrenia. AB - The inferior parietal lobe (IPL) is a center of multisensory integration, and both functional and structural MRI studies have found evidence that pathology in this region may contribute to disrupted sensory perception in schizophrenia. To further define this pathology, we used postmortem samples from the left and right IPL, to compare the thickness and volume of the upper (I-III) and lower (IV-VI) cortical layers. The samples were divided into supramarginal and angular gyri, and neuron density and size were measured in the supramarginal gyrus. The laminar thickness and volume measurements did not demonstrate significant changes in schizophrenia, but did show that the angular gyrus was thinner than the supramarginal gyrus, due to a difference mainly in the lower layers. Measurements of cortical thickness, neuron size and neuron density all showed some evidence of previously reported normal hemispheric differences. These asymmetries were reduced in schizophrenia, but the small changes were at the threshold of detection, and are discussed in the context of the sensitivity of the methods applied. PMID- 22304985 TI - An in vivo investigation of the initiation and progression of subchondral cysts in a rodent model of secondary osteoarthritis. AB - INTRODUCTION: Subchondral bone cysts (SBC) have been identified in patients with knee osteoarthritis (OA) as a cause of greater pain, loss of cartilage and increased chance of joint replacement surgery. Few studies monitor SBC longitudinally, and clinical research using three-dimensional imaging techniques, such as magnetic resonance imaging (MRI), is limited to retrospective analyses as SBC are identified within an OA patient cohort. The purpose of this study was to use dual-modality, preclinical imaging to monitor the initiation and progression of SBC occurring within an established rodent model of knee OA. METHODS: Eight rodents underwent anterior cruciate ligament transection and partial medial meniscectomy (ACLX) of the right knee. In vivo 9.4 T MRI and micro-computed tomography (micro-CT) scans were performed consecutively prior to ACLX and 4, 8, and 12 weeks post-ACLX. Resultant images were co-registered using anatomical landmarks, which allowed for precise tracking of SBC size and composition throughout the study. The diameter of the SBC was measured, and the volumetric bone mineral density (vBMD) was calculated within the bone adjacent to SBC. At 12 weeks, the ACLX and contralateral knees were processed for histological analysis, immunohistochemistry, and Osteoarthritis Research Society International (OARSI) pathological scoring. RESULTS: At 4 weeks post-ACLX, 75% of the rodent knees had at least 1 cyst that formed in the medial tibial plateau; by 12 weeks all ACLX knees contained SBC. Imaging data revealed that the SBC originate in the presence of a subchondral bone plate breach, with evolving composition over time. The diameter of the SBC increased significantly over time (P = 0.0033) and the vBMD significantly decreased at 8 weeks post-ACLX (P = 0.033). Histological analysis demonstrated positive staining for bone resorption and formation surrounding the SBC, which were consistently located beneath the joint surface with the greatest cartilage damage. Trabecular bone adjacent the SBC lacked viable osteocytes and, combined with bone marrow changes, indicated osteonecrosis. CONCLUSIONS: This study provides insight into the mechanisms leading to SBC formation in knee OA. The expansion of these lesions is due to stress-induced bone resorption from the incurred mechanical instability. Therefore, we suggest these lesions can be more accurately described as a form of OA-induced osteonecrosis, rather than 'subchondral cysts'. PMID- 22304986 TI - Legal liability and research ethics boards: the case of neuroimaging and incidental findings. AB - Neuroimaging research covers a wide range of intriguing issues from revealing brain structures to investigating what happens in our brain when we lie. The field appears to be thriving, but skepticism and alertness to the various ethical, scientific, policy and philosophical challenges associated with it also appear to be on the rise. One particularly complex issue concerns what to do with incidental findings that emerge during the course of neuroimaging research. Research ethics boards (REBs) play a central role in research oversight. In this paper, we will consider some of the potential issues associated with REB liability in negligence in the context of incidental findings in neuroimaging research. PMID- 22304987 TI - Picturing neuroscience research through a human rights lens: imaging first episode schizophrenic treatment-naive individuals. AB - In this paper we examine imaging research involving first-episode schizophrenic treatment-naive individuals (FESTNIs) through a legal human rights lens; in particular, the lens of the Additional Protocol to the Convention on Human Rights and Biomedicine Concerning Biomedical Research. We identify a number of ethical and legal hot spots highlighted by the Protocol, and offer a series of recommendations designed to ensure the human rights compatibility of this research. Subsequently, we argue that the lack of reporting on design elements related to ethical concerns frustrates commitments at the heart of the human rights approach, namely, transparency and openness to international scrutiny. To redress this problem, we introduce two norms for the first time: ethical transparency, and ethical reproducibility. When concluding, we offer a set of reporting guidelines designed to operationalize these norms in the context of imaging research involving FESTNIs. Though we will not make this case here, we believe that parallel reporting guidelines should be incorporated into other areas of research involving human subjects. PMID- 22304988 TI - BaFe12O19 single-particle-chain nanofibers: preparation, characterization, formation principle, and magnetization reversal mechanism. AB - BaFe(12)O(19) single-particle-chain nanofibers have been successfully prepared by an electrospinning method and calcination process, and their morphology, chemistry, and crystal structure have been characterized at the nanoscale. It is found that individual BaFe(12)O(19) nanofibers consist of single nanoparticles which are found to stack along the nanofiber axis. The chemical analysis shows that the atomic ratio of Ba/Fe is 1:12, suggesting a BaFe(12)O(19) composition. The crystal structure of the BaFe(12)O(19) single-particle-chain nanofibers is proved to be M-type hexagonal. The single crystallites on each BaFe(12)O(19) single-particle-chain nanofibers have random orientations. A formation mechanism is proposed based on thermogravimetry/differential thermal analysis (TG-DTA), X ray diffraction (XRD), and transmission electron microscopy (TEM) at six temperatures, 250, 400, 500, 600, 650, and 800 degrees C. The magnetic measurement of the BaFe(12)O(19) single-particle-chain nanofibers reveals that the coercivity reaches a maximum of 5943 Oe and the saturated magnetization is 71.5 emu/g at room temperature. Theoretical analysis at the micromagnetism level is adapted to describe the magnetic behavior of the BaFe(12)O(19) single-particle chain nanofibers. PMID- 22304989 TI - Validation of a mechanism to balance exercise difficulty in robot-assisted upper extremity rehabilitation after stroke. AB - BACKGROUND: The motivation of patients during robot-assisted rehabilitation after neurological disorders that lead to impairments of motor functions is of great importance. Due to the increasing number of patients, increasing medical costs and limited therapeutic resources, clinicians in the future may want patients to practice their movements at home or with reduced supervision during their stay in the clinic. Since people only engage in an activity and are motivated to practice if the outcome matches the effort at which they perform, an augmented feedback application for rehabilitation should take the cognitive and physical deficits of patients into account and incorporate a mechanism that is capable of balancing i.e. adjusting the difficulty of an exercise in an augmented feedback application to the patient's capabilities. METHODS: We propose a computational mechanism based on Fitts' Law that balances i.e. adjusts the difficulty of an exercise for upper-extremity rehabilitation. The proposed mechanism was implemented into an augmented feedback application consisting of three difficulty conditions (easy, balanced, hard). The task of the exercise was to reach random targets on the screen from a starting point within a specified time window. The available time was decreased with increasing condition difficulty. Ten subacute stroke patients were recruited to validate the mechanism through a study. Cognitive and motor functions of patients were assessed using the upper extremity section of the Fugl Meyer Assessment, the modified Ashworth scale as well as the Addenbrookes cognitive examination-revised. Handedness of patients was obtained using the Edinburgh handedness inventory. Patients' performance during the execution of the exercises was measured twice, once for the paretic and once for the non-paretic arm. Results were compared using a two-way ANOVA. Post hoc analysis was performed using a Tukey HSD with a significance level of p < 0.05. RESULTS: Results show that the mechanism was capable of balancing the difficulty of an exercise to the capabilities of the patients. Medians for both arms show a gradual decrease and significant difference of the number of successful trials with increasing condition difficulty (F(2;60) = 44.623; p < 0.01; eta(2) = 0.623) but no significant difference between paretic and non-paretic arm (F(1;60) = 3.768; p = 0.057; eta(2) = 0.065). Post hoc analysis revealed that, for both arms, the hard condition significantly differed from the easy condition (p < 0.01). In the non paretic arm there was an additional significant difference between the balanced and the hard condition (p < 0.01). Reducing the time to reach the target, i.e., increasing the difficulty level, additionally revealed significant differences between conditions for movement speeds (F(2;59) = 6.013; p < 0.01; eta(2) = 0.185), without significant differences for hand-closing time (F(2;59) = 2.620; p = 0.082; eta(2) = 0.09), reaction time (F(2;59) = 0.978; p = 0.383; eta(2) = 0.036) and hand-path ratio (F(2;59) = 0.054; p = 0.947; eta(2) = 0.002). The evaluation of a questionnaire further supported the assumption that perceived performance declined with increased effort and increased exercise difficulty leads to frustration. CONCLUSIONS: Our results support that Fitts' Law indeed constitutes a powerful mechanism for task difficulty adaptation and can be incorporated into exercises for upper-extremity rehabilitation. PMID- 22304990 TI - Heavy smoking during pregnancy as a marker for other risk factors of adverse birth outcomes: a population-based study in British Columbia, Canada. AB - BACKGROUND: Smoking during pregnancy is associated with known adverse perinatal and obstetrical outcomes as well as with socio-economic, demographic and other behavioural risk factors that independently influence outcomes. Using a large population-based perinatal registry, we assess the quantity of cigarettes smoked for the magnitude of adverse birth outcomes and also the association of other socio-economic and behavioural risk factors documented within the registry that influence pregnancy outcomes. Our goal was to determine whether number of cigarettes smoked could identify those in greatest need for comprehensive intervention programs to improve outcomes. METHODS: Our population-based retrospective study of singleton births from 2001 to 2006 (N = 237,470) utilized data obtained from the BC Perinatal Database Registry. Smoking data, self reported at the earliest prenatal visit, was categorized as: never, former, light (1 to 4), moderate (5 to 9), or heavy smoker (10 or more per day). Crude and adjusted odds ratios (AOR) with 95% confidence intervals (95% CI) were calculated using logistic regression models for smoking frequency and adverse birth outcomes. A partial proportional odds (pp-odds) model was used to determine the association between smoking status and other risk factors. RESULTS: There were 233,891 singleton births with available smoking status data. A significant dose dependent increase in risk was observed for the adverse birth outcomes small-for gestational age, term low birth weight and intra-uterine growth restriction. Results from the pp-odds model indicate heavy smokers were more likely to have not graduated high school: AOR (95% CI) = 3.80 (3.41-4.25); be a single parent: 2.27 (2.14-2.42); have indication of drug or alcohol use: 7.65 (6.99-8.39) and 2.20 (1.88-2.59) respectively, attend fewer than 4 prenatal care visits: 1.39 (1.23-1.58), and be multiparous: 1.59 (1.51-1.68) compared to light, moderate and non-smokers combined. CONCLUSION: Our data suggests that self reports of heavy smoking early in pregnancy could be used as a marker for lifestyle risk factors that in combination with smoking influence birth outcomes. This information may be used for planning targeted intervention programs for not only smoking cessation, but potentially other support services such as nutrition and healthy pregnancy education. PMID- 22304992 TI - 2011--year in review. PMID- 22304991 TI - Pretreatment of endothelial progenitor cells with osteopontin enhances cell therapy for peripheral vascular disease. AB - Tissue necrosis resulting from critical limb ischemia (CLI) leads to amputation in a significant number of patients. Autologous cell therapy using angiogenic cells such as endothelial progenitor cells (EPCs) holds promise as a treatment for CLI but a limitation of this treatment is that the underlying disease etiology that resulted in CLI may also contribute to dysfunction of the therapeutic EPCs. This study aimed to elucidate the mechanism of EPC dysfunction using diabetes mellitus as a model and to determine whether correction of this defect in dysfunctional EPCs ex vivo would improve the outcome after cell transplantation in the murine hind limb ischemia model. EPC dysfunction was confirmed in a homogenous population of patients with type 1 diabetes mellitus and a microarray study was preformed to identify dysregulated genes. Notably, the secreted proangiogenic protein osteopontin (OPN) was significantly downregulated in diabetic EPCs. Furthermore, OPN-deficient mice showed impaired recovery following hind limb ischemia, suggesting a critical role for OPN in postnatal neovascularization. EPCs isolated from OPN KO mice showed decreased ability to adhere to endothelial cells as well as impaired angiogenic potential. However, this dysfunction was reversed upon exposure to recombinant OPN, suggesting that OPN may act in an autocrine manner on EPCs. Indeed, exposure of OPN knockout (KO) EPCs to OPN was sufficient to induce the secretion of angiogenic proteins (IL-6, TGF-alpha, and FGF-alpha). We also demonstrated that vascular regeneration following hind limb ischemia in OPN KO mice was significantly improved upon injection of EPCs preexposed to OPN. We concluded that OPN acts in an autocrine manner on EPCs to induce the secretion of angiogenic proteins, thereby playing a critical role in EPC-mediated neovascularization. Modification of cells by exposure to OPN may improve the efficacy of autologous EPC transplantation via the enhanced secretion of angiogenic proteins. PMID- 22304993 TI - Intensive care admissions and outcome at the University of Calabar Teaching Hospital, Nigeria. AB - An intensive care unit (ICU) is for critically ill patients who are likely to benefit from the expertise care provided. The outcome is dependent on the available human and material resources. The University of Calabar Teaching Hospital is a 410-bed hospital. It has a 3-bed general ICU consisting of 2 adult and 1 pediatric beds. A retrospective analysis of all ICU admissions as well as the mortality rate during a 12-month period that spans April 2009 and March 2010 was done. The data were collected from the ICU admissions and nurses' report books. The data extracted were the patients ages, stratified to pediatric (0-18 years) and adult (>18 years); the source of admission, primary diagnosis, the duration of admission, and the patients who were ventilated were also noted. The outcome in terms of mortality was examined in relation to parameters stated above. Eighty-five patients were admitted during the 1-year period, with a bed occupancy rate of 23%. There were 11 (12.9%) pediatric patients and 74 (87.1%) adult patients. Sources of admissions were 64 (75.3%) patients from the operating room, 8 (9.4%) from the inpatient wards, and 13 (15.3%) from the accident and emergency department. Among the adult patients, there were 23 (31%) patients with trauma. There were 45 (61%) surgical patients and 6 (8%) medical patients. Sixteen (19%) patients were mechanically ventilated. The overall mortality was 28 (32.9%). Sixty-four percent of the mortality occurred during the first 24 hours of admission. A mortality rate of 83.3% was recorded among medical patients and 62.5% in those referred from the wards. In mechanically ventilated patients, the mortality rate was 62.5%. Ventilator malfunction, power failure, and oxygen exhaustion led to the unfavorable outcome in patients who were ventilated. In pediatric patients, the mortality rate was 45.5%. Early identification and referral of critically ill patients from the wards, availability of ventilator with battery backup, and maintenance of functioning equipment would reduce the high mortality rate recorded in the study. PMID- 22304994 TI - The determination of the efficiency of a Compton suppressed HPGe detector using Monte Carlo simulations. AB - A Compton suppressed high-purity germanium (HPGe) detector is well suited to the analysis of low levels of radioactivity in environmental samples. The difference in geometry, density and composition of environmental calibration standards (e.g. soil) can contribute to excessive experimental uncertainty to the measured efficiency curve. Furthermore multiple detectors, like those used in a Compton suppressed system, can add complexities to the calibration process. Monte Carlo simulations can be a powerful complement in calibrating these types of detector systems, provided enough physical information on the system is known. A full detector model using the Geant4 simulation toolkit is presented and the system is modelled in both the suppressed and unsuppressed mode of operation. The full energy peak efficiencies of radionuclides from a standard source sample is calculated and compared to experimental measurements. The experimental results agree relatively well with the simulated values (within ~5 - 20%). The simulations show that coincidence losses in the Compton suppression system can cause radionuclide specific effects on the detector efficiency, especially in the Compton suppressed mode of the detector. Additionally since low energy photons are more sensitive to small inaccuracies in the computational detector model than high energy photons, large discrepancies may occur at energies lower than ~100 keV. PMID- 22304995 TI - Synthesis and characterization of carboxyl terminated poly(methacrylic acid) grafted chitosan/bentonite composite and its application for the recovery of uranium(VI) from aqueous media. AB - A novel adsorbent poly(methacrylic acid)-grafted chitosan/bentonite (CTS-g PMAA/Bent) composite was prepared through graft copolymerization reaction of methacrylic acid and chitosan in the presence of bentonite (Bent) and N,N'- methylenebisacrylamide as a crosslinker. The composite was well characterized using FTIR, XRD, XPS, SEM-EDS, surface area and zeta potential analyzers. The adsorption behavior of the composite toward uranium(VI) from aqueous media was studied under varying operating conditions of pH, concentration of U(VI), contact time, adsorbent dose and temperature. The optimum pH range for U(VI) adsorption was 5.5 at 30 degrees C. Concentration and temperature dependent rate constants were evaluated using pseudo-second-order kinetic model. The equilibrium data were correlated with the Langmuir isotherm model with an endothermic behavior. The equilibrium U(VI) sorption capacity was estimated to be 117.2 mg g(-1) at 30 degrees C. For the quantitative recovery of 100 mg L(-1) U(VI) from 1.0 L simulated nuclear industry wastewater, a minimum adsorbent dosage of 2.0 g CTS-g PMAA/Bent was required. The calculated energy of activation (E(a) = 47.83 kJ/mol) was positively correlated with chemical adsorption process. The values of enthalpy, entropy and free energy of activation were calculated to explain the nature of adsorption process. Adsorption-desorption experiments over four cycles illustrate the feasibility of the repeated uses of this composite for the extraction of U(VI) from aqueous solutions. PMID- 22304996 TI - Nucleotide diversity and gene expression of Catalase and Glutathione peroxidase in irradiated Scots pine (Pinus sylvestris L.) from the Chernobyl exclusion zone. AB - In the Chernobyl exclusion zone forest trees have to tolerate and to adapt to ionizing radiation, therefore the molecular basis of their adaptive responses is of the utmost interest. Based on SNP analysis and real time PCR nucleotide diversity and expression profiles of gene fragments of catalase (Cat) and glutathione peroxidase (GPx), which are known as radical scavenging genes, were analysed in the needles of irradiated pine trees of the Chernobyl exclusion zone. In acutely and chronically irradiated trees (50 years old) planted before the accident a higher nucleotide diversity of Cat and more somatic mutations were found compared to their control. Chronically irradiated trees (20 years old) planted after the accident showed a similar nucleotide diversity of Cat compared to their control and in both collectives one somatic mutation was found. The nucleotide diversity of GPx was higher in all analysed trees compared to Cat. No somatic mutation events were found in GPx. For both gene fragments, no association between the received dose in a tree and the nucleotide diversity and mutation events was detected. The expression profiles of Cat and GPx in acutely and chronically and in chronically irradiated trees were similar. Compared to their corresponding control collectives, Cat was up-regulated and GPx slightly down-regulated. PMID- 22304997 TI - Variation in background concentrations and specific activities of 36Cl, 129I and U/Th-series radionuclides in surface waters. AB - Assessment of the potential environmental impacts of nuclear fuel waste involves multiple lines of argument, one of which is an evaluation of the possible increments to background concentrations of certain radionuclides. This is especially relevant for radionuclides such as (3)H, (36)Cl and (129)I where there is continuous cosmogenic or geogenic production. However, for (36)Cl and (129)I and certain U/Th-series radionuclides, data are scarce because the analysis methods are complex and costly. The present study used accelerator mass spectroscopy (AMS) to measure(36)Cl and (129)I in river waters throughout Canada. Radiochemical methods were used for (3)H and the selected U/Th-series radionuclides, and stable element concentrations were also determined. There were distinct differences in concentrations among the sites. Stable Cl and I tended to be at higher concentrations near the ocean or population centres. The (3)H was high in regions with power reactors. The (226)Ra, (235)U and (238)U concentrations were high in areas with known U mineralizations, as expected. The (36)Cl and (129)I concentrations were generally homogenous in mid-latitudes, but the (129)I concentration was lower in the one arctic site sampled. Because the stable and radioactive isotopes of Cl and I varied in response to different factors, the resulting specific activities were especially variable. Both Cl and I are homeostatically controlled in animals, thus it follows that dose from (36)Cl and (129)I will depend more closely on specific activity than concentration, and therefore the environmental increments of interest are in the specific activities rather than simply concentrations. PMID- 22304998 TI - 210Polonium content of small cetaceans from Southeastern Brazil. AB - The (210)Po concentration of muscle and liver samples obtained from dolphins stranded on beaches in the Southeastern region of Rio de Janeiro State was analyzed in the present study. The samples were primarily obtained from "Franciscana" (Pontoporia blainvillei) and "Guiana" dolphins (Sotalia guianensis); however, samples from four other species were also evaluated. The (210)Po concentration of muscle samples obtained from "Franciscana" dolphins (66.7+/-6.7, n=8)Bq kg(-1)w.w. was greater than that of "Guiana" dolphins (25.3+/ 5.7, n=8)Bq kg(-1)w.w. due to differences in the diets of these species. Alternatively, the (210)Po concentrations of liver samples obtained from different species were statically equivalent. Compared to the results described in the literature, the muscle samples evaluated in the present study displayed lower (210)Po concentrations, except for those obtained from "Franciscana" dolphins, which exhibited similar values. For "Franciscana" and "Guiana" dolphins, a clear relationship between the (210)Po concentration of muscle and liver samples and the size of the dolphin was not observed. PMID- 22304999 TI - Rapid removal of uranium from aqueous solutions using magnetic Fe3O4@SiO2 composite particles. AB - Rapid removal of U(VI) from aqueous solutions was investigated using magnetic Fe(3)O(4)@SiO(2) composite particles as the novel adsorbent. Batch experiments were conducted to study the effects of initial pH, amount of adsorbent, shaking time and initial U(VI) concentrations on uranium sorption efficiency as well as the desorbing of U(VI). The sorption of uranium on Fe(3)O(4)@SiO(2) composite particles was pH-dependent, and the optimal pH was 6.0. In kinetics studies, the sorption equilibrium can be reached within 180 min, and the experimental data were well fitted by the pseudo-second-order model, and the equilibrium sorption capacities calculated by the model were almost the same as those determined by experiments. The Langmuir sorption isotherm model correlates well with the uranium sorption equilibrium data for the concentration range of 20-200 mg/L. The maximum uranium sorption capacity onto magnetic Fe(3)O(4)@SiO(2) composite particles was estimated to be about 52 mg/g at 25 degrees C. The highest values of uranium desorption (98%) was achieved using 0.01 M HCl as the desorbing agent. Fe(3)O(4)@SiO(2) composite particles showed a good selectivity for uranium from aqueous solution with other interfering cation ions. Present study suggested that magnetic Fe(3)O(4)@SiO(2) composite particles can be used as a potential adsorbent for sorption uranium and also provided a simple, fast separation method for removal of heavy metal ion from aqueous solution. PMID- 22305000 TI - Validating the use of 137Cs and 210Pbex measurements to estimate rates of soil loss from cultivated land in southern Italy. AB - Soil erosion represents an important threat to the long-term sustainability of agriculture and forestry in many areas of the world, including southern Italy. Numerous models and prediction procedures have been developed to estimate rates of soil loss and soil redistribution, based on the local topography, hydrometeorology, soil type and land management. However, there remains an important need for empirical measurements to provide a basis for validating and calibrating such models and prediction procedures as well as to support specific investigations and experiments. In this context, erosion plots provide useful information on gross rates of soil loss, but are unable to document the efficiency of the onward transfer of the eroded sediment within a field and towards the stream system, and thus net rates of soil loss from larger areas. The use of environmental radionuclides, particularly caesium-137 ((137)Cs) and excess lead-210 ((210)Pb(ex)), as a means of estimating rates of soil erosion and deposition has attracted increasing attention in recent years and the approach has now been recognised as possessing several important advantages. In order to provide further confirmation of the validity of the estimates of longer-term erosion and soil redistribution rates provided by (137)Cs and (210)Pb(ex) measurements, there is a need for studies aimed explicitly at validating the results obtained. In this context, the authors directed attention to the potential offered by a set of small erosion plots located near Reggio Calabria in southern Italy, for validating estimates of soil loss provided by (137)Cs and (210)Pb(ex) measurements. A preliminary assessment suggested that, notwithstanding the limitations and constraints involved, a worthwhile investigation aimed at validating the use of (137)Cs and (210)Pb(ex) measurements to estimate rates of soil loss from cultivated land could be undertaken. The results demonstrate a close consistency between the measured rates of soil loss and the estimates provided by the (137)Cs and (210)Pb(ex) measurements and can therefore been seen as validating the use of these fallout radionuclides to document soil erosion rates in that environment. Further studies are clearly required to exploit other opportunities for validation in contrasting environments and under different land use conditions. PMID- 22305001 TI - Distribution of 152Eu and 154Eu in the 'alluvial soil-rhizosphere-plant roots' system. AB - Accumulation of (152)Eu and (15)(4)Eu isotopes in bulk soil and rhizosphere soil in the near-field zone of influence of the Krasnoyarsk Mining and Chemical Combine was studied. An uneven distribution of specific activity of Eu isotopes was observed, with the gross specific activities of the isotopes in the bulk soil exceeding those of the rhizosphere. In the most contaminated locations the fine and the coarse granulometric fractions are enriched with the isotopes. A laboratory experiment indicated potential removal of soluble Eu isotopes by river flood waters may amount to 3% of the total Eu in both bulk and rhizosphere soils. The root system of plants growing in the contaminated territory accumulates (152)Eu and (154)Eu, although the isotopes were not discovered in aboveground parts of plants. Root-hairs were found to be the most contaminated. PMID- 22305002 TI - Nuclear event zero-time calculation and uncertainty evaluation. AB - It is important to know the initial time, or zero-time, of a nuclear event such as a nuclear weapon's test, a nuclear power plant accident or a nuclear terrorist attack (e.g. with an improvised nuclear device, IND). Together with relevant meteorological information, the calculated zero-time is used to help locate the origin of a nuclear event. The zero-time of a nuclear event can be derived from measured activity ratios of two nuclides. The calculated zero-time of a nuclear event would not be complete without an appropriately evaluated uncertainty term. In this paper, analytical equations for zero-time and the associated uncertainty calculations are derived using a measured activity ratio of two nuclides. Application of the derived equations is illustrated in a realistic example using data from the last Chinese thermonuclear test in 1980. PMID- 22305003 TI - Measurement of the 36Cl deposition flux in central Japan: natural background levels and seasonal variability. AB - Essential parameters for the applications of (36)Cl as a tracer in groundwater studies include the initial (36)Cl/Cl ratio, at the time of recharge, and/or the natural background deposition flux of (36)Cl in the recharge area. To facilitate the hydrological use of (36)Cl in central Japan, this study aimed to obtain a precise estimate of the long-term average local (36)Cl flux and to characterize its seasonal variability. The (36)Cl in precipitation was continuously monitored in Tsukuba, central Japan over a period of >5 years. The (36)Cl flux showed a clear seasonal variation with an annual peak during the spring, which was attributed to the seasonal variability of tropopause height. The long-term average (36)Cl flux (32+/-2atoms m(-2)s(-1)), estimated from the measured data, was consistent with the prediction from the (36)Cl latitudinal fallout model scaled using the global mean production rate of 20atoms m(-2)s(-1). The initial (36)Cl/Cl ratio was estimated to be (41+/-6)*10(-15), which is similar to that of pre-bomb groundwater in the Tsukuba Upland. An observation period covering an 11 year solar cycle would yield more accurate estimates of the values, given the increased (36)Cl flux during the solar minimum. PMID- 22305004 TI - Long-lived fusions of human haematological tumour cells and B-lymphoblastoid cells induce tumour antigen-specific cytotoxic T-cell responses in vitro. AB - Tumour-specific cytotoxic T-cells (CTL) are important anti-cancer immune effectors. Most tumour cells, however, do not stimulate effective anti-tumour immune responses, in vivo or in vitro. To enhance tumour cell immunogenicity, we fused human tumour cells from haematological malignancies with the B lymphoblastoid cell line (LCL), HMy2, to generate a panel of long-lived, self replicating LCL/tumour hybrid cell lines. The LCL/tumour hybrid cell lines expressed HLA class I and class II molecules, CD80 and CD86, and a range of known tumour associated antigens (TAAs). In vitro stimulation of PBLs from healthy, HLA A2+ individuals by hybrid cell lines induced tumour antigen-specific CTLs to TAAs, including survivin, MAGE-A1, NY-ESO-1 and WT-1. Individual hybrid cell lines simultaneously induced CTL to multiple TAAs. In vitro stimulation of PBL from 2 patients with acute myeloid leukaemia by autologous LCL/tumour hybrid cell lines induced CTL capable of killing the patient's own tumour cells. Our data show, for the first time, that hybrid cell lines formed by fusion of HMy2 cells and haematological tumour cells induce tumour- and tumour antigen-specific cytotoxic T-cell responses in vitro. Hybrid cell lines such as those described may represent novel reagents for use in the immunotherapy of haematological malignancies. PMID- 22305005 TI - The role of probiotics in gastrointestinal surgery. AB - The intestinal microbiota, which is a complex and dynamic population of different bacterial species, represents an important contribution to the health of the host. This microbiota plays a key role by promoting the integrity of the epithelial barrier and the development of mucosal immunity. However, under some stressful situations, such as after gastrointestinal surgery, infectious complications may originate from the intestinal microbiota of the patient. This phenomenon is known as the gut origin of sepsis hypothesis. However, the supply of probiotics has beneficial effects under similar conditions despite some controversial results. Therefore, it is important to carefully assess the efficacy of probiotics in the prevention and treatment of complications in surgical patients and to evaluate the safety of its use. This review provides an overview of the proposed mechanisms of probiotic action and the significant progress in this field, mainly concerning gastrointestinal surgery. PMID- 22305006 TI - Lipoic acid attenuates high-fat-diet-induced oxidative stress and B-cell-related immune depression. AB - OBJECTIVE: This study investigated whether spleen oxidative stress induced by a high-fat diet (HFD) influences the expression of genes involved in B-cell activation, thus leading to B-cell-related immunosuppression. METHODS: Male C57BL/6 mice were randomly assigned to one of three groups with eight mice in each group. The control group consumed an ordinary diet (4.9% fat, w/w). The other two groups were fed an HFD (21.2% fat) and an HFD plus 0.1% lipoic acid (LA). After 10 wk, plasma and spleen oxidative stress biomarkers including superoxide dismutase, catalase, glutathione peroxidase, total antioxidant capacity, reduced glutathione/oxidized glutathione ratio, and malondialdehyde were examined. The B-cell-related immune function was evaluated by examining the number of B cells, and the apoptotic percentages of splenic lymphocytes were determined by flow cytometry. Furthermore, the B-cell activation and reactive oxygen species scavenger-related genes differentially expressed between mice fed an HFD and those fed an HFD supplemented with LA were identified through complementary DNA microarray. RESULTS: The HFD induced marked decreases in the number of B cells and significantly increased the apoptotic percentages of splenic lymphocytes, accompanied by oxidative stress and increased oxidative damage, in the plasma and spleen. In addition, complementary DNA array analysis results showed that the HFD induced the decreased expression of genes associated with antioxidant defense, such as superoxide dismutase-3 (1.5-fold), metallothionein-1 (3.03-fold), glutathione peroxidase-5 (17.15-fold), and peroxiredoxin-4 (1.5), and B-cell activation, such as immunoglobulin heavy chain 6 (2.46-fold), immunoglobulin kappa-chain (1.74-fold), Fc receptor (1.41-fold), and RAS-related C3 botulinum substrate-1 (7.46). The LA supplement prevented the buildup of oxidative stress and upregulated related gene expressions. CONCLUSION: These results indicate a role for LA as a possible effective supplement with an HFD to prevent the development of oxidative stress and to attenuate B-cell damnification by increasing the gene expression of the B-cell receptor signaling pathway. PMID- 22305007 TI - Regulation of circadian behavioral output via a MicroRNA-JAK/STAT circuit. AB - Although molecular components of the circadian clock are known, mechanisms that transmit signals from the clock and produce rhythmic behavior are poorly understood. We find that the microRNA miR-279 regulates the JAK/STAT pathway to drive rest:activity rhythms in Drosophila. Overexpression of microRNA miR-279 or miR-279 deletion attenuates rest:activity rhythms. Oscillations of the clock protein PERIOD are normal in pacemaker neurons lacking miR-279, suggesting that miR-279 acts downstream of the clock. We identify the JAK/STAT ligand, Upd, as a target of miR-279 and show that knockdown of Upd rescues the behavioral phenotype of miR-279 mutants. Manipulations of the JAK/STAT pathway also disrupt circadian rhythms. In addition, central clock neurons project in the vicinity of Upd expressing neurons, providing a possible physical connection by which the central clock could regulate JAK/STAT signaling to control rest:activity rhythms. PMID- 22305008 TI - Human intestinal mast cells are a potent source of multiple chemokines. AB - Mast cells are key effector cells of immediate type allergic reactions. Upon activation they release a broad array of pre-stored and de novo synthesized mediators including immunoregulatory cytokines and chemokines. Here, we analyzed the chemokine profile expressed by mature human mast cells. Human mast cells were isolated from intestinal tissue and cultured with stem cell factor (SCF) in the presence or absence of IL-4 for 10d. Cells were stimulated by cross-linking of the high affinity IgE receptor (FcepsilonRI) and/or by SCF. Chemokine and chemokine receptor mRNA expression was determined by real-time RT-PCR and chemokine release was measured by multiplex bead immunoassay. Out of 43 chemokines and 19 chemokine receptors human intestinal mast cells express 27 chemokines and nine chemokine receptors. Twelve chemokines (CCL1, CCL2, CCL3, CCL4, CCL5, CCL7, CCL18, CCL20, CXCL2, CXCL3, CXCL8, and XCL1) were more than four-fold up-regulated in response to FcepsilonRI cross-linking. Combination of pre-culture with IL-4 and/or stimulation with SCF in addition to FcepsilonRI cross-linking further increased the antigen-dependent expression of mRNA for most chemokines. In contrast, the expression of CCL20, CXCL2, and CXCL3 was strongly inhibited by IL-4 treatment. In conclusion, human intestinal mast cells express a broad spectrum of different chemokines underlining their important role as immunoregulatory cells. Furthermore, combined treatment with IL-4 and SCF increases the antigen-mediated expression and release of multiple chemokines, but IL-4 priming inhibits the expression of CCL20, CXCL2, and CXCL3. PMID- 22305009 TI - Memory deficits for non-amnestic mild cognitive impairment. AB - Non-amnestic mild cognitive impairment (naMCI) is one of the clinical subtypes of mild cognitive impairment (MCI). However, the characteristics of memory deficits in naMCI as assessed by clinical neuropsychological evaluations are not clear. In this study, a battery of neuropsychological tests was administered to 122 cognitively normal controls (NC), 133 amnestic mild cognitive impairment (aMCI) patients, and 72 naMCI patients. The results showed that in individuals with naMCI, episodic memory, and other cognitive domains were impaired. The Prospective Memory Test (PMT) event-based prospective memory (EBPM), the Symbol Digit Modalities Test (SDMT) Accidental Memory, Stick test (ST) visuoconstructional memory, and ST Working Memory were impaired, yet did not reach the level of aMCI. Semantic memory was affected to a degree comparable with aMCI. Some functions like Auditory Verbal Learning Test (AVLT) recognition, and Judgment of Confidence (JOC) were maintained, as well as PMT Time-Based Prospective Memory (TBPM). This study verified that memory impairment among individuals with naMCI was mainly in memory functions mediated by the frontotemporal cortex. PMID- 22305010 TI - [Multidetector computed tomography assessment of the degree of differentiation of bronchial carcinoid tumors]. AB - OBJECTIVE: To define the CT findings for bronchial carcinoid tumors and to determine whether these findings enable these tumors to be classified as typical or atypical. MATERIAL AND METHODS: We reviewed the chest CT studies performed between 1 January 2001 and 31 December 2009 in patients at our hospital diagnosed with bronchial carcinoid tumors. The sample consisted of 52 patients (23 women and 29 men) with a mean age of 47 years (range 11-77 years). The 52 cases were classified as typical or atypical on the basis of the following radiological findings: size, location, focality, type of growth, calcifications, signs secondary to bronchial obstruction, and the presence of significant lymph node enlargement or metastases. These findings were then compared with the histological findings. RESULTS: Typical carcinoid tumors were the most prevalent (46 cases). The variables associated with atypical tumors were: male sex, advanced age at onset, and size >3cm. The accuracy of CT in classifying atypical tumors correctly increased with the number of variables indicative of atypical carcinoid tumors. A negative result for atypical nature made it possible to rule out an atypical carcinoid tumor in 95% of the cases. CONCLUSION: CT is useful for defining and characterizing carcinoid tumors into typical or atypical, although a precise formula for differentiating between the two types remains to be defined. PMID- 22305011 TI - Thermal imaging of nanostructures by quantitative optical phase analysis. AB - We introduce an optical microscopy technique aimed at characterizing the heat generation arising from nanostructures, in a comprehensive and quantitative manner. Namely, the technique permits (i) mapping the temperature distribution around the source of heat, (ii) mapping the heat power density delivered by the source, and (iii) retrieving the absolute absorption cross section of light absorbing structures. The technique is based on the measure of the thermal induced refractive index variation of the medium surrounding the source of heat. The measurement is achieved using an association of a regular CCD camera along with a modified Hartmann diffraction grating. Such a simple association makes this technique straightforward to implement on any conventional microscope with its native broadband illumination conditions. We illustrate this technique on gold nanoparticles illuminated at their plasmonic resonance. The spatial resolution of this technique is diffraction limited, and temperature variations weaker than 1 K can be detected. PMID- 22305012 TI - Optimal dose of contrast medium for depiction of hypervascular HCC on dynamic MDCT. AB - PURPOSE: The purpose of this study is to prospectively investigate the optimal dose of contrast medium for the depiction of hypervascular hepatocellular carcinoma (HCC) during the hepatic arterial phase (HAP), portal venous phase (PVP) and delayed phase (DP) of dynamic MDCT. MATERIALS AND METHODS: The study included 128 patients, out of these patients, 36 patients were found to have 56 hypervascular HCCs. Sixty-three patients were assigned to receive a dose of 525 mgI/kg with protocol A, and 62 received a dose of 630 mgI/kg with protocol B. Measurements of the attenuation values of the abdominal aorta, portal vein, hepatic vein, hepatic parenchyma and HCC during the HAP, PVP and DP were taken. Tumor-liver contrast (TLC) was calculated from the attenuation value of the hepatic parenchyma and HCC. RESULTS: The aortic attenuation value with protocol B (351, 166, and 132 HU) was significantly higher than that with protocol A (313, 153, and 120 HU) during all the phases, (P<0.01 for all phases). The hepatic enhancement from unenhanced baseline with protocol B (25.2, 63.6, 50.6 HU) was significantly higher than that with protocol A (20.2, 55.1 and 43.0 HU) during all the phases, (P<0.01 for all phases). The TLC with protocol B (37.4, -11.8 and -13.6 HU) was significantly higher than that with protocol A (28.0, -9.8 and 12.1 HU) during HAP (P=0.042). CONCLUSION: The administration of 630 mgI/kg of body weight depicts hypervascular HCC more clearly during HAP and shows sufficient hepatic enhancement of 50 HU during DP. PMID- 22305013 TI - 18F-FDG PET or PET/CT for detection of metastatic lymph nodes in patients with endometrial cancer: a systematic review and meta-analysis. AB - The present study assessed the diagnostic performances of 18F-FDG PET or PET/CT in detecting pelvic and/or paraaortic lymph node metastasis in patients with endometrial cancer. METHODS: Through a search of MEDLINE (January 1998 to March 2011), an overall weighted average for sensitivity and specificity as well as pooled estimates of positive and negative likelihood ratios were calculated. A summary receiver-operating-characteristics (sROC) curve was constructed and the area under the sROC curve (AUC) was calculated. I-square was calculated to explore heterogeneity. RESULTS: The present study included 243 patients from seven studies. Results indicated a lack of significant heterogeneity for sensitivity and specificity (I2<50% and p>0.05). The overall pooled estimates for sensitivity and specificity of FDG-PET or PET/CT scans in the detection of pelvic and/or paraaortic metastasis were 63.0% (95% CI, 48.7-75.7%) and 94.7% (95% CI, 90.4-97.4%), respectively. The positive likelihood ratio was 10.465 (95% CI, 5.646-19.396) and the negative likelihood ratio 0.399 (95% CI, 0.284-0.560). The AUC was 0.9533. The overall diagnostic accuracy (Q* index) was 89.5%. Conclusion The high positive likelihood value confirms the reliability of a positive FDG-PET or PET/CT to detect pelvic and/or paraaortic lymph nodes metastasis in patients with untreated endometrial cancer. FDG-PET or PET/CT may prove beneficial to surgeons when selecting appropriate patients on whom to perform lymphadenectomy. PMID- 22305014 TI - The dimensions and characteristics of the subepidermal nerve plexus in human skin -terminal Schwann cells constitute a substantial cell population within the superficial dermis. AB - BACKGROUND: The skin constitutes the largest sensorial organ. Its nervous system consists of different types of afferent nerve fibers which spread out immediately beneath the skin surface to sense temperature, touch and pain. OBJECTIVE: Our aim was to investigate the dimension and topographic relationship of the different nerve fibers of the subepidermal nerve plexus in human hairy skin and to analyze numbers and marker expression of terminal Schwann cells. METHODS: Nerve fibers and Schwann cells were investigated on dermal sheet preparations and thick sections of skin from various body regions of 10 individuals. RESULTS: The dimension of subepidermal nerve fibers varied between different body sites with highest values in chest skin (100 +/- 18 mm/mm(2)) and lowest in posterior forearm skin (53 +/- 10 mm/mm(2)). The majority of fibers (85.79%) were unmyelinated, thus representing C-fibers, of which 7.84% were peptidergic. Neurofilament-positive fibers (A-fibers) accounted for 14.21% and fibers positive for both neurofilament and myelin (Abeta-fibers) for only 0.18%. The number of Schwann cells varied in accordance with nerve fiber length from 453 +/- 108 on chest skin to 184 +/- 58/mm(2) in skin of the posterior forearm. Terminal Schwann cells showed a marker profile comparable to Schwann cells in peripheral nerves with the notable exception of expression of NGFr, NCAM, L1CAM and CD146 on myelinating Schwann cells in the dermis but not in peripheral nerves. CONCLUSION: Our data show that terminal Schwann cells constitute a substantial cell population within the papillary dermis and that both nerve fiber length and Schwann cell numbers vary considerably between different body sites. PMID- 22305015 TI - Possible role of infrared or heat in sun-induced changes of dermis of human skin in vivo. PMID- 22305016 TI - TNF-alpha increases lipogenesis via JNK and PI3K/Akt pathways in SZ95 human sebocytes. AB - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is an important pathophysiologic factor involved in the development of acne. However, its role is unclear. OBJECTIVE: To explore the lipogenic effect by TNF-alpha and possible molecular mechanisms in sebocyte. METHODS: Using SZ95 human sebocytes, lipid formation by TNF-alpha was assessed by Oil Red O, Nile Red staining and thin layer chromatography (TLC). Expression of lipogenic genes and activation of mitogen-activated protein kinase as well as Akt were examined by real-time polymerase chain reaction and/or Western blot analysis. Activation of peroxisome proliferator-activated receptor (PPAR) was evaluated by luciferase assay using PPAR response element containing reporter plasmids. Involvement of c-Jun N terminal kinase (JNK) and Akt in TNF-alpha-induced lipogenesis was investigated by molecule specific small interfering RNA and inhibitors. RESULTS: TNF-alpha treatment significantly increased formation of lipid droplets in accordance with up-regulated expression of FAS and activation of SREBP-1, but not PPARs. Suppression of phosphorylated JNK by the JNK inhibitor SP600125 greatly diminished TNF-alpha-induced expression of FAS and SREBP-1. TNF-alpha could not induce both expression of lipogenic proteins and lipid synthesis when Akt expression was attenuated with siRNA. CONCLUSIONS: TNF-alpha induces lipogenesis in SZ95 human sebocytes through the JNK and phosphoinositide-3-kinase/Akt pathways. These results will be valuable in developing therapeutic strategies for control of seborrhea and acne. PMID- 22305017 TI - Migration of human melanocytes into keratinocyte monolayers in vitro. PMID- 22305018 TI - Determination of 20(S)-protopanaxadiol ocotillol type epimers in rat plasma by liquid chromatography tandem mass spectrometry. AB - To study stereoselectivity in the pharmacokinetics of each epimer, a rapid, specific and reliable liquid chromatography tandem mass spectrometry method has been established for simultaneous quantitation of both epimers in rat plasma. Plasma samples were pretreated by liquid-liquid extraction. Chromatographic separations were performed on a Shim-pack XR-ODS C18 column (50 mm * 2.1mm, i.d., 2.2 MUm) with an isocratic elution. Both epimers and the internal standard tanshinone II A were ionized with an ESI source operated in positive ion mode and measured by selective reactions monitoring mode. Calibration curve was linear over the concentration range of 1-1000 ng/mL with the lower limit of quantitation of 1 ng/mL for both epimers. Intra and inter-day precisions were less than 6.7% and 9.5%, and the accuracy was within +/-5.8% for both epimers. The validated method has been successfully applied to a pharmacokinetic study of the two epimers in rats after oral administration. PMID- 22305019 TI - Signal evolution in the local magnetic field of a capillary -- analogy to the damped driven harmonic oscillator. AB - The temporal behavior of the magnetization decay caused by the local inhomogeneous magnetic field of a capillary is analyzed. Respecting the diffusion of the spins surrounding the capillary and the strength of the susceptibility difference between the capillary and the surrounding medium, it is possible to distinguish different dephasing regimes. Each dephasing regime can be related to a certain characteristic form of the magnetization decay. If the influence of the diffusion dominates, the magnetization exhibits a monotonic decay. In the opposite case of dominating influence of the susceptibility effects, the magnetization shows an oscillating behavior. It can be shown that the dephasing process is closely related to the behavior of a damped driven harmonic oscillator. PMID- 22305020 TI - Optimal real-time estimation in diffusion tensor imaging. AB - Diffusion tensor imaging (DTI) constitutes the most used paradigm among the diffusion-weighted magnetic resonance imaging (DW-MRI) techniques due to its simplicity and application potential. Recently, real-time estimation in DW-MRI has deserved special attention, with several proposals aiming at the estimation of meaningful diffusion parameters during the repetition time of the acquisition sequence. Specifically focusing on DTI, the underlying model of the noise present in the acquired data is not taken into account, leading to a suboptimal estimation of the diffusion tensor. In this paper, we propose an optimal real time estimation framework for DTI reconstruction in single-coil acquisitions. By including an online estimation of the time-changing noise variance associated to the acquisition process, the proposed method achieves the sequential best linear unbiased estimator. Results on both synthetic and real data show that our method outperforms those so far proposed, reaching the best performance of the existing proposals by processing a substantially lower number of diffusion images. PMID- 22305021 TI - Association of human bocavirus 1 infection with respiratory disease in childhood follow-up study, Finland. AB - Human bocavirus 1 (HBoV1) DNA is frequently detected in the upper airways of young children with respiratory symptoms. Because of its persistence and frequent co-detection with other viruses, however, its etiologic role has remained controversial. During 2009-2011, using HBoV1 IgM, IgG, and IgG-avidity enzyme immunoassays and quantitative PCR, we examined 1,952 serum samples collected consecutively at 3- to 6-month intervals from 109 constitutionally healthy children from infancy to early adolescence. Primary HBoV1 infection, as indicated by seroconversion, appeared in 102 (94%) of 109 children at a mean age of 2.3 years; the remaining 7 children were IgG antibody positive from birth. Subsequent secondary infections or IgG antibody increases were evident in 38 children and IgG reversions in 10. Comparison of the seroconversion interval with the next sampling interval for clinical events indicated that HBoV1 primary infection, but not secondary immune response, was significantly associated with acute otitis media and respiratory illness. PMID- 22305022 TI - Cannabis--a valuable drug that deserves better treatment. PMID- 22305023 TI - Reprogramming of the infant brain by surgery with general anesthesia. PMID- 22305024 TI - Cannabinoid hyperemesis: a case series of 98 patients. AB - OBJECTIVE: To promote wider recognition and further understanding of cannabinoid hyperemesis (CH). PATIENTS AND METHODS: We constructed a case series, the largest to date, of patients diagnosed with CH at our institution. Inclusion criteria were determined by reviewing all PubMed indexed journals with case reports and case series on CH. The institution's electronic medical record was searched from January 1, 2005, through June 15, 2010. Patients were included if there was a history of recurrent vomiting with no other explanation for symptoms and if cannabis use preceded symptom onset. Of 1571 patients identified, 98 patients (6%) met inclusion criteria. RESULTS: All 98 patients were younger than 50 years of age. Among the 37 patients in whom duration of cannabis use was available, most (25 [68%]) reported using cannabis for more than 2 years before symptom onset, and 71 of 75 patients (95%) in whom frequency of use was available used cannabis more than once weekly. Eighty-four patients (86%) reported abdominal pain. The effect of hot water bathing was documented in 57 patients (58%), and 52 (91%) of these patients reported relief of symptoms with hot showers or baths. Follow-up was available in only 10 patients (10%). Of those 10, 7 (70%) stopped using cannabis and 6 of these 7 (86%) noted complete resolution of their symptoms. CONCLUSION: Cannabinoid hyperemesis should be considered in younger patients with long-term cannabis use and recurrent nausea, vomiting, and abdominal pain. On the basis of our findings in this large series of patients, we propose major and supportive criteria for the diagnosis of CH. PMID- 22305025 TI - Attention-deficit/hyperactivity disorder after early exposure to procedures requiring general anesthesia. AB - OBJECTIVE: To study the association between exposure to procedures performed under general anesthesia before age 2 years and development of attention deficit/hyperactivity disorder (ADHD). PATIENTS AND METHODS: Study patients included all children born between January 1, 1976, and December 31, 1982, in Rochester, MN, who remained in Rochester after age 5. Cases of ADHD diagnosed before age 19 years were identified by applying stringent research criteria. Cox proportional hazards regression assessed exposure to procedures requiring general anesthesia (none, 1, 2 or more) as a predictor of ADHD using a stratified analysis with strata based on a propensity score including comorbid health conditions. RESULTS: Among the 5357 children analyzed, 341 ADHD cases were identified (estimated cumulative incidence, 7.6%; 95% confidence interval [CI], 6.8%-8.4%). For children with no postnatal exposure to procedures requiring anesthesia before the age of 2 years, the cumulative incidence of ADHD at age 19 years was 7.3% (95% CI, 6.5%-8.1%). For single and 2 or more exposures, the estimates were 10.7% ( 95% CI, 6.8%-14.4%) and 17.9% ( 95% CI, 7.2%-27.4%), respectively. After adjusting for gestational age, sex, birth weight, and comorbid health conditions, exposure to multiple (hazard ratio, 1.95; 95% CI, 1.03-3.71), but not single (hazard ratio,1.18; 95% CI, 0.79-1.77), procedures requiring general anesthesia was associated with an increased risk for ADHD. CONCLUSION: Children repeatedly exposed to procedures requiring general anesthesia before age 2 years are at increased risk for the later development of ADHD even after adjusting for comorbidities. PMID- 22305026 TI - Recurrent urinary tract infection and urinary Escherichia coli in women ingesting cranberry juice daily: a randomized controlled trial. AB - OBJECTIVE: To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6 month period in women ingesting cranberry vs placebo juice daily. PATIENTS AND METHODS: Premenopausal women with a history of recent UTI were enrolled from November 16, 2005, through December 31, 2008, at 2 centers and randomized to 1 of 3 arms: 4 oz of cranberry juice daily, 8 oz of cranberry juice daily, or placebo juice. Time to UTI (symptoms plus pyuria) was the main outcome. Asymptomatic bacteriuria, adherence, and adverse effects were assessed at monthly visits. RESULTS: A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days. The cumulative rate of UTI was 0.29 in the cranberry juice group and 0.37 in the placebo group (P=.82). The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 0.68 (95% confidence interval, 0.33-1.39; P=.29). The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (43.5%) in the cranberry juice group and 8 of 10 (80.0%) in the placebo group (P=.07). The mean dose adherence was 91.8% and 90.3% in the cranberry juice group vs the placebo group. Minor adverse effects were reported by 24.2% of those in the cranberry juice group and 12.5% in the placebo group (P=.07). CONCLUSION: Cranberry juice did not significantly reduce UTI risk compared with placebo. The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger, well-powered studies of women with recurrent UTI. The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00128128. PMID- 22305027 TI - Generalizability of epidemiological findings and public health decisions: an illustration from the Rochester Epidemiology Project. AB - OBJECTIVE: To illustrate the problem of generalizability of epidemiological findings derived from a single population using data from the Rochester Epidemiology Project and from the US Census. METHODS: We compared the characteristics of the Olmsted County, Minnesota, population with the characteristics of populations residing in the state of Minnesota, the Upper Midwest, and the entire United States. RESULTS: Age, sex, and ethnic characteristics of Olmsted County were similar to those of the state of Minnesota and the Upper Midwest from 1970 to 2000. However, Olmsted County was less ethnically diverse than the entire US population (90.3% vs 75.1% white), more highly educated (91.1% vs 80.4% high school graduates), and wealthier ($51,316 vs $41,994 median household income; 2000 US Census data). Age- and sex-specific mortality rates were similar for Olmsted County, the state of Minnesota, and the entire United States. CONCLUSION: We provide an example of analyses and comparisons that may guide the generalization of epidemiological findings from a single population to other populations or to the entire United States. PMID- 22305028 TI - My treatment approach to patients with diffuse large B-cell lymphoma. AB - My favored treatment approach for patients with diffuse large B-cell lymphoma continues to evolve. Diffuse large B-cell lymphoma can now be cured in more than 50% of patients. This is a result of improved definitions of the disease, improved diagnostic capabilities, better staging and restaging techniques, a useful prognostic index to guide therapeutic decisions, and the development of increasingly effective therapies. Positron emission tomographic scans have improved the accuracy of both staging and restaging. Findings on a positron emission tomographic scan at the end of therapy are the best predictors of a good treatment outcome. Numerous subtypes of diffuse large B-cell lymphoma have been identified that require specific treatment approaches. For example, plasmablastic lymphoma typically lacks CD20 and does not benefit from treatment with rituximab. Diffuse large B-cell lymphoma originating in specific extranodal sites such as the central nervous system, testes, and skin presents special problems and requires specific treatment approaches. A subgroup of diffuse large B-cell lymphoma with a very high proliferative rate seems to have a poor outcome when treated with CHOP-R and does better with regimens used for patients with Burkitt lymphoma. New insights into the biology of these disorders are likely to further change treatment approaches. Recognition that diffuse large B-cell lymphoma is not one disease, but a variety of clinicopathologic syndromes provides the opportunity to further improve our ability to benefit patients. PMID- 22305029 TI - Blurred boundaries: the therapeutics and politics of medical marijuana. AB - For 5 millennia, Cannabis sativa has been used throughout the world medically, recreationally, and spiritually. From the mid-19th century to the 1930s, American physicians prescribed it for a plethora of indications, until the federal government started imposing restrictions on its use, culminating in 1970 with the US Congress classifying it as a Schedule I substance, illegal, and without medical value. Simultaneous with this prohibition, marijuana became the United States' most widely used illicit recreational drug, a substance generally regarded as pleasurable and relaxing without the addictive dangers of opioids or stimulants. Meanwhile, cannabis never lost its cachet in alternative medicine circles, going mainstream in 1995 when California became the first of 16 states to date to legalize its medical use, despite the federal ban. Little about cannabis is straightforward. Its main active ingredient, delta-9 tetrahydrocannabinol, was not isolated until 1964, and not until the 1990s were the far-reaching modulatory activities of the endocannabinoid system in the human body appreciated. This system's elucidation raises the possibility of many promising pharmaceutical applications, even as draconian federal restrictions that hamstring research show no signs of softening. Recreational use continues unabated, despite growing evidence of marijuana's addictive potential, particularly in the young, and its propensity for inducing and exacerbating psychotic illness in the susceptible. Public approval drives medical marijuana legalization efforts without the scientific data normally required to justify a new medication's introduction. This article explores each of these controversies, with the intent of educating physicians to decide for themselves whether marijuana is panacea, scourge, or both. PubMed searches were conducted using the following keywords: medical marijuana, medical cannabis, endocannabinoid system, CB1 receptors, CB2 receptors, THC, cannabidiol, nabilone, dronabinol, nabiximols, rimonabant, marijuana legislation, marijuana abuse, marijuana dependence, and marijuana and schizophrenia. Bibliographies were hand searched for additional references relevant to clarifying the relationships between medical and recreational marijuana use and abuse. PMID- 22305030 TI - Recognition and management of nonrelaxing pelvic floor dysfunction. AB - Nonrelaxing pelvic floor dysfunction is not widely recognized. Unlike in pelvic floor disorders caused by relaxed muscles (eg, pelvic organ prolapse or urinary incontinence, both of which often are identified readily), women affected by nonrelaxing pelvic floor dysfunction may present with a broad range of nonspecific symptoms. These may include pain and problems with defecation, urination, and sexual function, which require relaxation and coordination of pelvic floor muscles and urinary and anal sphincters. These symptoms may adversely affect quality of life. Focus on the global symptom complex, rather than the individual symptoms, may help the clinician identify the condition. The primary care provider is in a position to intervene early, efficiently, and effectively by (1) recognizing the range of symptoms that might suggest nonrelaxing pelvic floor dysfunction, (2) educating patients, (3) performing selective tests when needed to confirm the diagnosis, and (4) providing early referral for physical therapy. PMID- 22305031 TI - 33-year-old woman with epigastric pain and hematemesis. PMID- 22305032 TI - Mechanisms of resistance and clinical relevance of resistance to beta-lactams, glycopeptides, and fluoroquinolones. AB - The widespread use of antibiotics has resulted in a growing problem of antimicrobial resistance in the community and hospital settings. Antimicrobial classes for which resistance has become a major problem include the beta-lactams, the glycopeptides, and the fluoroquinolones. In gram-positive bacteria, beta lactam resistance most commonly results from expression of intrinsic low-affinity penicillin-binding proteins. In gram-negative bacteria, expression of acquired beta-lactamases presents a particular challenge owing to some natural spectra that include virtually all beta-lactam classes. Glycopeptide resistance has been largely restricted to nosocomial Enterococcus faecium strains, the spread of which is promoted by ineffective infection control mechanisms for fecal organisms and the widespread use of colonization-promoting antimicrobials (especially cephalosporins and antianaerobic antibiotics). Fluoroquinolone resistance in community-associated strains of Escherichia coli, many of which also express beta lactamases that confer cephalosporin resistance, is increasingly prevalent. Economic and regulatory forces have served to discourage large pharmaceutical companies from developing new antibiotics, suggesting that the antibiotics currently on the market may be all that will be available for the coming decade. As such, it is critical that we devise, test, and implement antimicrobial stewardship strategies that are effective at constraining and, ideally, reducing resistance in human pathogenic bacteria. PMID- 22305033 TI - Impaired fasting plasma glucose and stroke risk. PMID- 22305035 TI - Influence of alcohol on perioperative cognitive decline. PMID- 22305037 TI - Isidor Rabi-1944 Nobel laureate in physics. PMID- 22305039 TI - Large atrial myxoma causing dynamic obstruction of the mitral valve and atrial fibrillation. PMID- 22305040 TI - An afucosylated anti-CD20 monoclonal antibody with greater antibody-dependent cellular cytotoxicity and B-cell depletion and lower complement-dependent cytotoxicity than rituximab. AB - The objective of this study was to characterize the in vitro and in vivo activity of a novel afucosylated rituximab (BLX-300) expressed in a Lemna aquatic plant based system free of zoonotic pathogens. The glycosylation of BLX-300 was shown to be homogeneous, composed of a single major N-glycan species without detectable fucose or xylose. Target cell binding and induction of apoptosis were similar for BLX-300 and rituximab. Antibody-dependent cellular cytotoxicity (ADCC) was increased by BLX-300 versus rituximab in phenylalanine/phenylalanine (F/F), phenylalanine/valine (F/V) and valine/valine (V/V) genotype donors, as indicated by respective log reductions of 0.82, 1.07 and 0.92 in EC(50). BLX-300 also showed greater B-cell depletion than rituximab in whole blood from donors of F/F, F/V and V/V genotype in vitro and cynomolgus monkeys in vivo. Temporal changes in circulating levels of BLX-300 and rituximab were similar in cynomolgus monkeys. Complement-dependent cytotoxicity (CDC) was attenuated by BLX-300 relative to rituximab, as judged by a log increase of 0.51 in EC(50). The higher ADCC and B cell depletion suggest a potential improvement in effectiveness and potency, while lower CDC may mitigate infusion toxicity. PMID- 22305041 TI - Nanoscale zero-valent iron: future prospects for an emerging water treatment technology. AB - For the past 15 years, nanoscale metallic iron (nZVI) has been investigated as a new tool for the treatment of contaminated water and soil. The technology has reached commercial status in many countries worldwide, however is yet to gain universal acceptance. This review summarises our contemporary knowledge of nZVI aqueous corrosion, manufacture and deployment, along with methods to enhance particle reactivity, stability and subsurface mobility. Reasons for a lack of universal acceptance are also explored. Key factors include: concerns over the long-term fate, transformation and ecotoxicity of nZVI in environmental systems and, a lack of comparable studies for different nZVI materials and deployment strategies. It is highlighted that few investigations to date have examined systems directly analogous to the chemistry, biology and architecture of the terrestrial environment. Such emerging studies have highlighted new concerns, including the prospect for remobilisation of heavy metals and radionuclides over extended periods. The fundamental importance of being able to accurately predict the long-term physical, chemical and biological fate of contaminated sites following nZVI treatment is emphasised and, as part of this, a universal empirical testing framework for nZVI is suggested. PMID- 22305043 TI - Sunscreen use and availability among female collegiate athletes. AB - BACKGROUND: Each year more than 250,000 athletes participate on National Collegiate Athletic Association (NCAA) teams. The majority of outdoor NCAA athletes, however, do not use sunscreen on a daily basis. Previous research notes that sunscreen availability represents the main barrier to use among collegiate athletes. OBJECTIVE: We sought to explore the effect of sunscreen availability on its application among outdoor collegiate athletes. METHODS: Participants (n = 83) on NCAA Division IA female golf teams were randomized to form treatment and control groups. Treatment group players placed study-supplemented sunscreen in their golf bags and locker rooms during the study period. Both groups completed self-administered surveys at the beginning and end of the 4-week investigation. RESULTS: The athletes for whom sunscreen was placed in the locker room and bags exhibited a statistically greater use of sunscreen at the end of the study compared with the control group (P = .01). Provision of readily available sunscreen in the locker room resulted in an average of 1.13 more days per week of sunscreen use, after adjustment for baseline use (P = .008). In addition, players with ready access to sunscreen during competitions increased their reapplication, although not significantly, by nearly 20% (P = .10). Sunscreen reapplication during practice did not change for either group. LIMITATIONS: Future investigations should target a larger population of both male and female outdoor collegiate athletes. CONCLUSIONS: The application of sunscreen increased significantly when athletes had easy access to sunscreen during practice and competition. These findings highlight a major opportunity to improve sun protective behaviors among this vulnerable population. PMID- 22305042 TI - An overview of clinical and experimental treatment modalities for port wine stains. AB - Port wine stains (PWS) are the most common vascular malformation of the skin, occurring in 0.3% to 0.5% of the population. Noninvasive laser irradiation with flashlamp-pumped pulsed dye lasers (selective photothermolysis) currently comprises the gold standard treatment of PWS; however, the majority of PWS fail to clear completely after selective photothermolysis. In this review, the clinically used PWS treatment modalities (pulsed dye lasers, alexandrite lasers, neodymium:yttrium-aluminum-garnet lasers, and intense pulsed light) and techniques (combination approaches, multiple passes, and epidermal cooling) are discussed. Retrospective analysis of clinical studies published between 1990 and 2011 was performed to determine therapeutic efficacies for each clinically used modality/technique. In addition, factors that have resulted in the high degree of therapeutic recalcitrance are identified, and emerging experimental treatment strategies are addressed, including the use of photodynamic therapy, immunomodulators, angiogenesis inhibitors, hypobaric pressure, and site-specific pharmaco-laser therapy. PMID- 22305044 TI - Novel systemic drugs under investigation for the treatment of psoriasis. AB - In the last few years, there has been progress in identifying some of the risk genes for psoriasis. This has resulted in a major impetus toward drug development as many of the same pathways and processes identified in psoriasis have been shown to have major roles in other chronic inflammatory diseases, suggesting that psoriasis can be used as a treatment model for many other diseases. This has resulted in a shift in research toward a select number of biological processes and has been accompanied by a surge in drug development with over 20 systemic agents currently in clinical testing for psoriasis, many of which target the pathways identified through genetic and basic research. Although it is too early to tell for many of these agents how effective and safe they will be, and where they will fit into treatment algorithms, it is evident that our range of options in treating this often perplexing disease will greatly increase in the future. PMID- 22305045 TI - Blood pressure and associated factors in a North African adolescent population. a national cross-sectional study in Tunisia. AB - BACKGROUND: In southern and eastern Mediterranean countries, changes in lifestyle and the increasing prevalence of excess weight in childhood are risk factors for high blood pressure (BP) during adolescence and adulthood. The aim of this study was to evaluate the BP status of Tunisian adolescents and to identify associated factors. METHODS: A cross-sectional study in 2005, based on a national, stratified, random cluster sample of 1294 boys and 1576 girls aged 15-19 surveyed in home visits. The socio-economic and behavioral characteristics of the adolescents were recorded. Overweight/obesity were assessed by Body Mass Index (BMI) from measured height and weight (WHO, 2007), abdominal obesity by waist circumference (WC). BP was measured twice during the same visit. Elevated BP was systolic (SBP) or diastolic blood pressure (DBP) >= 90th of the international reference or >= 120/80 mm Hg for 15-17 y., and SBP/DBP >= 120/80 mm Hg for 18-19 y.; hypertension was SBP/DBP >= 95th for 15-17 y. and >= 140/90 mm Hg for 18-19 y. Adjusted associations were assessed by logistic regression. RESULTS: The prevalence of elevated BP was 35.1%[32.9-37.4]: higher among boys (46.1% vs. 33.3%; P < 0.0001); 4.7%[3.8-5.9] of adolescents had hypertension. Associations adjusted for all covariates showed independent relationships with BMI and WC: - obesity vs. no excess weight increased elevated BP (boys OR = 2.1[1.0-4.2], girls OR = 2.3[1.3-3.9]) and hypertension (boys OR = 3.5[1.4-8.9], girls OR = 5.4[2.2 13.4]), - abdominal obesity (WC) was also associated with elevated BP in both genders (for boys: 2nd vs. 1st tertile OR = 1.7[1.3-2.3], 3rd vs.1st tertile OR = 2.8[1.9-4.2]; for girls: 2nd vs. 1st tertile OR = 1.6[1.2-2.1], 3rd vs.1st tertile OR = 2.1[1.5-3.0]) but only among boys for hypertension. Associations with other covariates were weaker: for boys, hypertension increased somewhat with sedentary lifestyle, while elevated BP was slightly more prevalent among urban girls and those not attending school. CONCLUSION: Within the limits of BP measurement on one visit only, these results suggest that Tunisian adolescents of both genders are likely not spared from early elevated BP. Though further assessment is likely needed, the strong association with overweight/obesity observed suggests that interventions aimed at changing lifestyles to reduce this main risk factor may also be appropriate for the prevention of elevated BP. PMID- 22305046 TI - [The meaning of standardized language NANDA-NIC-NOC intensive care nurses in Madrid: a phenomenological approach]. AB - Nursing standardized language is a tool that makes it possible to integrate a theoretical framework of problem identification, interventions and outcomes in care. Its use in the difference care settings is varied. In the case of intensive care units, it is necessary to study the implications that integration of this language would have in nursing area. OBJECTIVE: To describe the meaning of standardized NANDA-NIC-NOC language for the nurses working in Intensive Care Units in Madrid. METHOD: A phenomenological qualitative study was conducted. INCLUSION CRITERIA: ICU in Madrid of nurses with one year or more experience at the time of the study who were working in the ICU. SAMPLE: Purposive and Snowball sampling technique. DATA COLLECTION: Unstructured interviews, personal documents (letters, diaries). Interviews were recorded and transcribed verbatim for later analysis. ANALYSIS: Giorgi proposal. Identifying meaning units, groups of common senses and themes. RESULTS: Three themes made up the meaning of standardized language in intensive care nursing. "Living integrating 2 sides of the same coin", "living a conceptual imposition", and "living a development opportunity and professional autonomy". CONCLUSIONS: There is a gap in the theory of language and its clinical application. Nurses report feeling imposition of a specific conceptual language. This creates the construction of a hierarchy between nurses based on the use of NANDA-NIC-NOC. Even so, the standardized language is experienced as a professional development opportunity. PMID- 22305047 TI - [The ICU nurse: a key factor for the success of continuous dialysis techniques]. PMID- 22305048 TI - Human and porcine hepatitis E viruses, southeastern Bolivia. PMID- 22305049 TI - Impact of two iron(III) chelators on the iron, cadmium, lead and nickel accumulation in poplar grown under heavy metal stress in hydroponics. AB - Poplar (Populus jacquemontiana var. glauca cv. Kopeczkii) was grown in hydroponics containing 10 MUM Cd(II), Ni(II) or Pb(II), and Fe as Fe(III) EDTA or Fe(III) citrate in identical concentrations. The present study was designed to compare the accumulation and distribution of Fe, Cd, Ni and Pb within the different plant compartments. Generally, Fe and heavy-metal accumulation were higher by factor 2-7 and 1.6-3.3, respectively, when Fe(III) citrate was used. Iron transport towards the shoot depended on the Fe(III) chelate and, generally, on the heavy metal used. Lead was accumulated only in the root. The amounts of Fe and heavy metals accumulated by poplar were very similar to those of cucumber grown in an identical way, indicating strong Fe uptake regulation of these two Strategy I plants: a cultivar and a woody plant. The Strategy I Fe uptake mechanism (i.e. reducing Fe(III) followed by Fe(II) uptake), together with the Fe(III) chelate form in the nutrient solution had significant effects on Fe and heavy metal uptake. Poplar appears to show phytoremediation potential for Cd and Ni, as their transport towards the shoot was characterized by 51-54% and 26-48% depending on the Fe(III) supply in the nutrient solution. PMID- 22305050 TI - Interaction of proline, sugars, and anthocyanins during photosynthetic acclimation of Arabidopsis thaliana to drought stress. AB - The relationships among photosynthetic acclimation, proline (Pro), soluble sugar (SS), and anthocyanin (An) accumulation in Arabidopsis thaliana leaves to the onset of drought stress (OnDS), mild (MiDS) and moderate drought stress (MoDS), were evaluated. As leaf water content (LWC) decreased, metabolic concentrations (Pro, SS, and An) increased and were negatively and significantly correlated with LWC. Thus, these metabolites may have an important role in the acclimation process to drought stress (DS). No correlations among Pro, SS and An accumulation with the quantum efficiency of PSII photochemistry (Phi(PSII)) and the excitation pressure (1-q(P)) were observed under DS. This implies that, while metabolites increased in a drought-dependent way, PSII activity did not decrease in the same pattern. Our results indicated that, under MoDS, A. thaliana leaves were able to maintain oxidative compounds such as malondialdeyde, an end product of lipid peroxidation, within the range of control leaves, and to cope with oxidative damage, as was evident by the decreased excitation pressure (1-q(P)) and similar (ns difference) Phi(PSII) to that of control leaves. In addition, a statistically significant increased accumulation of Pro, SS and An was recorded only under MoDS compared to controls. The better PSII functioning of MoDS Arabidopsis leaves may reflect the greater capacity of these leaves to undertake key metabolic adjustments, including increased Pro, SS and An accumulation, to maintain a higher antioxidant protection and a better balance between light capture and energy use. PMID- 22305051 TI - Metaphorically feeling: comprehending textural metaphors activates somatosensory cortex. AB - Conceptual metaphor theory suggests that knowledge is structured around metaphorical mappings derived from physical experience. Segregated processing of object properties in sensory cortex allows testing of the hypothesis that metaphor processing recruits activity in domain-specific sensory cortex. Using functional magnetic resonance imaging (fMRI) we show that texture-selective somatosensory cortex in the parietal operculum is activated when processing sentences containing textural metaphors, compared to literal sentences matched for meaning. This finding supports the idea that comprehension of metaphors is perceptually grounded. PMID- 22305052 TI - Development of an automated method to detect sitting pivot transfer phases using biomechanical variables: toward a standardized method. AB - BACKGROUND: Sitting pivot transfer (SPT) is one of the most important, but at the same time strenuous at the upper extremity, functional task for spinal cord injured individuals. In order to better teach this task to those individuals and to improve performance, a better biomechanical understanding during the different SPT phases is a prerequisite. However, no consensus has yet been reached on how to depict the different phases of the SPT. The definition of the phases of the SPT, along with the events characterizing these phases, will facilitate the interpretation of biomechanical outcome measures related to the performance of SPTs as well as strengthen the evidence generated across studies. METHODS: Thirty five individuals with a spinal cord injury performed two SPTs between seats of similar height using their usual SPT technique. Kinematics and kinetics were recorded using an instrumented transfer assessment system. Based on kinetic and kinematic measurements, a relative threshold-based algorithm was developed to identify four distinct phases: pre-lift, upper arm loading, lift-pivot and post lift phases. To determine the stability of the algorithm between the two SPTs, Student t-tests for dependent samples were performed on the absolute duration of each phase. RESULTS: The mean total duration of the SPT was 2.00 +/- 0.49 s. The mean duration of the pre-lift, upper arm loading, lift-pivot and post-lift phases were 0.74 +/- 0.29 s, 0.28 +/- 0.13 s, 0.72 +/- 0.24 s, 0.27 +/- 0.14 s whereas their relative contributions represented approximately 35%, 15%, 35% and 15% of the overall SPT cycle, respectively. No significant differences were found between the trials (p = 0.480-0.891). CONCLUSION: The relative threshold-based algorithm used to automatically detect the four distinct phases of the SPT, is rapid, accurate and repeatable. A quantitative and thorough description of the precise phases of the SPT is prerequisite to better interpret biomechanical findings and measure task performance. The algorithm could also become clinically useful to refine the assessment and training of SPTs. PMID- 22305053 TI - Orthotopic heart transplantation in patients with metabolic risk factors. AB - BACKGROUND: The aim of this study was to evaluate the impact of metabolic risk factors on mortality rates after orthotopic heart transplantation (OHT). METHODS: Adult patients undergoing OHT between 1998 and 2008 were identified in the United Network for Organ Sharing registry. The impact of metabolic risk factors (hypertension, diabetes mellitus, and obesity) on mortality post-OHT was evaluated in a Cox proportional hazards regression analysis adjusted for other variables associated with survival in univariate analysis (exploratory p value<0.2). Kaplan-Meier survival estimates were compared with the log-rank test. RESULTS: A total of 15,960 eligible patients underwent OHT during the study period. There were 6,368 (39.9%) patients with none of these risk factors, 6,138 (38.5%) with 1 risk factor, 2,811 (17.6%) with 2 risk factors, and 643 (4.0%) who had all 3 risk factors. After adjusting for other significant variables influencing survival, each individual risk factor independently increased the likelihood of mortality post-OHT (hypertension: HR 1.10 [1.03 to 1.17]; diabetes: HR 1.22[1.13 to 1.31]; obesity: HR 1.17 [1.10 to 1.26], each p<0.01). There was an exponential trend of increasing mortality with the addition of each risk factor (r2=0.99, p<0.001) such that patients with all 3 risk factors had a 63% increased mortality compared with those with no risk factors (HR 1.63 [1.42 to 1.88], p<0.001). There was also a significant trend in declining 5-year survival rates with an increasing number of risk factors: 0 (74.7%), 1 (71.3%), 2 (68.2%), and 3 (63.1%) (p<0.001). CONCLUSIONS: This large-cohort study demonstrates that an increasing number of metabolic risk factors in OHT recipients is associated with exponential increases in postoperative mortality rates. PMID- 22305054 TI - Acute exacerbation of usual interstitial pneumonia after resection of lung cancer. AB - BACKGROUND: Acute exacerbation of usual interstitial pneumonia is one of the most life-threatening complications after resection of lung cancer. It is important to detect patients at high risk for acute exacerbation. The purpose of this study was to investigate the incidence of postoperative acute exacerbation and the importance of the finding of honeycombing in predicting the risk of it. METHODS: From 992 consecutive pulmonary resections for lung cancer, the background lung was retrospectively assessed histologically. Preoperative chest computed tomographic images of those patients with histologically proven usual interstitial pneumonia were retrospectively reassessed and classified into three groups: typical honeycombing, possible honeycombing, and no honeycombing. Records of patients who experienced postoperative acute exacerbation were extracted from the clinical database, and the correlation between computed tomographic findings and incidence of acute exacerbation was analyzed. RESULTS: Of the 992 lung cancer patients, 12 (1.2%) experienced postoperative acute exacerbation. Usual interstitial pneumonia was histologically confirmed in 249 patients, and 4.8% of them experienced postoperative acute exacerbation. No patient without usual interstitial pneumonia experienced it. Preoperative computed tomographic images were available in 205 of the 249 patients. Postoperative acute exacerbation developed in 13.6% of patients (6 of 44 patients) in the typical honeycombing group, 6.4% of patients (5 of 78 patients) in the possible honeycombing group, and 0% of patients (0 of 83 patients) in the no-honeycombing group. Compared with the no-honeycombing group, the incidence of acute exacerbation in the typical and possible honeycombing groups was significantly higher (p=0.001, p=0.025, respectively). CONCLUSIONS: Physicians should consider the finding of possible honeycombing, as well as typical honeycombing, a potential risk factor for acute exacerbation after pulmonary resection for lung cancer. PMID- 22305055 TI - Cox-Maze IV results for patients with lone atrial fibrillation versus concomitant mitral disease. AB - BACKGROUND: This study compared Cox-Maze IV (CMIV) outcomes for the treatment of atrial fibrillation (AF) in patients with lone AF vs those with AF and mitral valve (MV) disease. METHODS: Since 2002, 200 patients have undergone a CMIV procedure for lone AF (n=101) or concomitantly with MV operations (n=99). Preoperative, perioperative, and late outcomes between these groups were compared. Data were collected prospectively and reported at 3, 6, and 12 months. RESULTS: Lone AF patients had AF of longer duration; patients with AF and MV disease were older, with larger left atria and worse New York Heart Association classification (p<0.05). Operative mortality (1% vs 4%, p>0.05, respectively) was similar between both groups. Perioperative atrial tachyarrhythmias were more prevalent in patients with concomitant MV operations (57% vs 41%, p=0.03); however, freedom from AF and antiarrhythmics was similar for both groups at 12 months (76% and 77%). The only predictor for atrial tachyarrhythmia recurrence or arrhythmic drug dependence was failure to isolate the posterior left atrium (p<0.01). CONCLUSIONS: Patients with AF and MV disease have distinct comorbidities compared with patients with lone AF. However, the CMIV is safe and effective in both groups and should be considered for patients with AF undergoing MV operations. Patients with MV disease had more atrial tachyarrhythmias at 3 months, but freedom from AF and antiarrhythmics was similar to patients with lone AF at 1 year. The posterior left atrium should be isolated in every patient, because this was the only predictor for failure of the CMIV for either group. PMID- 22305056 TI - Endobronchial ultrasonography with a guide sheath in the diagnosis of benign peripheral diseases. AB - BACKGROUND: For appropriate treatment, such as the selection of antibiotics or initiation of steroid therapy, correctly diagnosing benign pulmonary diseases located at the periphery is vital. This study assessed the usefulness of bronchoscopy using endobronchial ultrasonography with a guide sheath (EBUS-GS) in the diagnosis of benign pulmonary diseases, especially those presenting peripheral nodular lesions. METHODS: We retrospectively reviewed 159 patients with 171 peripheral pulmonary lesions (PPLs) that were subsequently diagnosed as benign diseases. To examine the role of bronchoscopy with EBUS-GS, the contribution of bronchoscopy was classified into 4 categories. We also retrospectively reviewed 24 patients with 25 PPLs that were subsequently diagnosed as benign diseases by bronchoscopy without EBUS-GS (historical control). RESULTS: The ultimate diagnosis of 171 PPLs included 45 cases of mycobacteriosis, 45 cases of bronchiolitis obliterans organizing pneumonia/chronic organized pneumonia (BOOP), 23 cases of bacterial pneumonia, 13 abscesses, 11 cases of sarcoidosis, and 34 other benign diseases. Among them, a definitive diagnosis was obtained by bronchoscopy with EBUS-GS in 99 lesions (58%). Lesions in which the probe was positioned within the lesion had a higher diagnostic yield (64%) than did lesions in which the probe was positioned adjacent to the lesion (52%) or outside the lesion (20%; P=0.01). The diagnostic yield of bronchoscopy with EBUS-GS was higher compared with that of the historical control (58% versus 28%; P=0.04). CONCLUSIONS: Bronchoscopy using EBUS GS is a reasonable option as a diagnostic procedure for PPLs, even if they are suspected to be benign in nature. PMID- 22305057 TI - Use of glucocorticoids and risk of breast cancer: a Danish population-based case control study. AB - INTRODUCTION: Glucocorticoids are widely prescribed drugs. In the human body, glucocorticoid is the main stress hormone and controls a variety of physiological and cellular processes, including metabolism and immune response. It belongs to the same steroid superfamily as estrogens, which are known to play a role in breast cancer. However, the effect of glucocorticoid use on the risk of breast cancer is not clear. METHODS: We conducted a case-control study using population based medical databases from Northern Denmark (1.8 million inhabitants) to investigate the association between glucocorticoid prescriptions and breast cancer risk. The study included 9,488 incident breast cancer cases diagnosed between 1994 and 2008 and 94,876 population controls. We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) associating glucocorticoid use with breast cancer occurrence, controlling for prescriptions of postmenopausal hormone replacement therapy, anti-diabetics, immunosuppressive drugs, and hospital diagnosis of obesity, diabetes, chronic pulmonary diseases and autoimmune diseases. RESULTS: We found no effect on breast cancer risk in ever users (> 2 prescriptions) of any glucocorticoids (adjusted odds ratio (aOR) = 1.0; 95% CI: 0.96, 1.1), systemic glucocorticoids (aOR = 1.0; 95% CI: 0.96, 1.1), or inhaled glucocorticoids (aOR = 1.0; 95% CI: 0.95, 1.1), each compared to never users of any glucocorticoids. Associations for recent use (preceding two years) and former use (more than two years earlier) were near null in all dose categories (low, medium and high number of prescriptions). Intensity of systemic glucocorticoid use (cumulative prednisolone equivalent doses), regardless of duration (< 1, 1 to 5, 5+ years), was also not associated with breast cancer risk. CONCLUSIONS: Overall, our study provides no evidence that glucocorticoid use affects the risk of breast cancer. PMID- 22305058 TI - High-frequency ultrasound in the evaluation of cerebral intraventricular haemorrhage in preterm rabbit pups. AB - Cerebral intraventricular haemorrhage (IVH) is the most common cause of severe neurologic impairment following preterm birth in human infants. Ideally, an animal model for cerebral IVH should allow for reliable noninvasive evaluation of haemorrhagic extension and of subsequent development of posthaemorrhagic ventricular dilatation (PHVD). The aim of this study was to evaluate the use of high-frequency ultrasound (HFU) in premature rabbit pups with cerebral IVH induced by IP glycerol injection. Serial examinations using HFU enabled an accurate description of haemorrhagic extension and measurement of progressive PHVD over 72 h. The coefficient of variation for inter- and intraobserver variability in two measurements of ventricular size was less than 8.8% and 9.3%, respectively. Repeated ultrasound-guided intraventricular injection and sampling could be performed in vivo excluding requirement of stereotactic procedures and sedation. Application of HFU is a powerful tool for the evaluation of mechanisms involved in cerebral IVH and PHVD in the preterm rabbit pup model. PMID- 22305059 TI - New microembolus size estimator for peripheral blood vessels. AB - Several factors affecting the power of Doppler scattered signal and, consequently, microembolus size estimation, may be eliminated when assessing the microembolus size via multiple measurements. A new microembolus size estimator is proposed based on the ratio of microembolus scattering cross-section in two directions and for two emission frequencies. Theoretical considerations indicate that the estimation of size of microembolic elements should be independent of the spatial distribution of the wave intensity, tissue attenuation and hardware factors. The simulation results indicate that this estimation only slightly depends on the material of the microembolus and acoustic properties of blood. The experimental results indicate that the accuracy of median size estimation increases with microembolus size. The measurement error is less than 27% for microemboli with median diameter larger than 360 MUm. The method is constrained to the estimation of microembolus size in the vessels of extremities. PMID- 22305060 TI - Effect of surface architecture on in vivo ultrasound contrast persistence of targeted size-selected microbubbles. AB - Ultrasound molecular imaging is a powerful diagnostic modality using microbubbles coated with targeting ligands specific for endothelial biomarkers. The circulation persistence of ligand-bearing contrast agents is a key determinant in their contrast enhancement and targeting capability. Prior studies have shown that targeted microbubbles with ligands attached to the shell using the conventional exposed-ligand architecture (ELA) could trigger undesired ligand induced complement activation and decreased circulation time. Microbubbles with the buried-ligand architecture (BLA), however, were found to inhibit complement activation and prolong circulation time. In the present study, we extended the stealth BLA microbubble design to size-selected (4 to 5-MUm diameter) microbubbles targeted with cyclic RGD peptide using the postlabeling technique. Microbubble circulation persistence was measured in the healthy mouse kidney using a Visualsonics Vevo 770 scanner operating at 40 MHz in fundamental mode. The circulation persistence for targeted BLA microbubbles was significantly longer compared with their ELA counterparts and similar to no-ligand controls. Use of the BLA instead of the ELA increased the circulation half-life approximately two-fold. Analysis of the time-intensity and time-fluctuation curves with a two-compartment pharmacokinetic model showed a minimal degree of nonspecific vascular adhesion for any group. These results demonstrate the importance of surface architecture in the design of targeted microbubbles for ultrasound molecular imaging. PMID- 22305061 TI - Adipose tissue-derived stem cell treatment prevents renal disease progression. AB - Adipose tissue-derived stem cells (ASCs) are an attractive source of stem cells with regenerative properties that are similar to those of bone marrow stem cells. Here, we analyze the role of ASCs in reducing the progression of kidney fibrosis. Progressive renal fibrosis was achieved by unilateral clamping of the renal pedicle in mice for 1 h; after that, the kidney was reperfused immediately. Four hours after the surgery, 2 * 10(5) ASCs were intraperitoneally administered, and mice were followed for 24 h posttreatment and then at some other time interval for the next 6 weeks. Also, animals were treated with 2 * 10(5) ASCs at 6 weeks after reperfusion and sacrificed 4 weeks later to study their effect when interstitial fibrosis is already present. At 24 h after reperfusion, ASC-treated animals showed reduced renal dysfunction and enhanced regenerative tubular processes. Renal mRNA expression of IL-6 and TNF was decreased in ASC-treated animals, whereas IL-4, IL-10, and HO-1 expression increased despite a lack of ASCs in the kidneys as determined by SRY analysis. As expected, untreated kidneys shrank at 6 weeks, whereas the kidneys of ASC-treated animals remained normal in size, showed less collagen deposition, and decreased staining for FSP-1, type I collagen, and Hypoxyprobe. The renal protection seen in ASC-treated animals was followed by reduced serum levels of TNF-alpha, KC, RANTES, and IL-1alpha. Surprisingly, treatment with ASCs at 6 weeks, when animals already showed installed fibrosis, demonstrated amelioration of functional parameters, with less tissue fibrosis observed and reduced mRNA expression of type I collagen and vimentin. ASC therapy can improve functional parameters and reduce progression of renal fibrosis at early and later times after injury, mostly due to early modulation of the inflammatory response and to less hypoxia, thereby reducing the epithelial-mesenchymal transition. PMID- 22305062 TI - Effect of salt treatment on phenolic compounds and antioxidant activity of two Mesembryanthemum edule provenances. AB - Mesembryanthemum edule L. is an edible and medicinal halophyte widespread in Tunisia seashore. In this study, parameters of oxidative stress, phenolic compounds and antioxidant activities were comparatively investigated in two M. edule provenances (Jerba and Bizerte, respectively sampled from arid and humid bioclimatic stages). Plants were subjected to 0, 300 and 600mM NaCl treatment under glasshouse conditions. Results showed that M. edule response to salinity depends on provenance (P), salt treatment (T) and their interaction (P*T). (T) affected more significantly the oxidative stress parameters and antioxidant activities than (P) and (P*T). Conversely, (P) was much affluent for tannin polymerization degree and interaction between the two factors (P*T) was more determinants for analyzed antioxidant parameters. The higher salt tolerance of Jerba plants was associated with low levels of malondialdehyde and of electrolyte leakage mainly at 600mM NaCl. Besides, antioxidant activities of Jerba provenance, were more efficient than Bizerte. In addition, avicularin was the major phenolic in both provenances. This compound concentration increased with salinity in Jerba shoots, while it was reduced in Bizerte especially at 600mM NaCl. Overall, the higher salt tolerance of plants from Jerba provenance, and to a lower extent of those from Bizerte, may be partly related to their better capacity to limit oxidative damage when salt-challenged, and this is likely the result of redistribution in phenolic composition. Besides, abiotic factors such as salinity could be determinant in antioxidant potentiality of this medicinal plant. PMID- 22305063 TI - Role of pathogen-induced volatiles in the Nicotiana tabacum-Golovinomyces cichoracearum interaction. AB - Plant injuries activate signal transduction cascades mediated by the plant hormones, which lead to enhanced expression of defence related genes and/or to changes in the emission of volatile organic compounds that can act as semiochemicals. In this research we demostrated that infection with the biotrophic pathogen Golovinomyces cichoracearum (DC.) V.P. Heluta (ex Erysiphe cichoracearum DC.), the causal agent of powdery mildew, led in the susceptible host Nicotiana tabacum L. cv Havana 425 to an increased emission of volatile compounds including Methyl-jasmonate (MeJA), (E)-2-hexenal and (E)-beta-ocimene. Furthermore we investigated the role of these volatiles in the plant-pathogen interaction. Exogenous application of MeJA induced in tobacco an increase in the transcripts level of the defence related genes lipoxygenase, allene oxide cyclase and defensin and a decrease in the severity of the infection. Qualitative and quantitative differences in volatile compounds emission were showed also in MeJA treated plants, where the emission of (E)-beta-ocimene was significantly increased instead (E)-2-hexenal was not detected. Application of (E)-2-hexenal reduced the severity of powdery mildew while application of (E)-beta-ocimene did not. Since (E)-2-hexenal did not activate in tobacco the accumulation of the above reported genes transcripts and the plant cell death, the reduction of the infection severity could be attributable to its inhibitory activity on the fungal germ tube growth. Our data highlight the contributions of natural substances that can act, directly or indirectly, against phytopathogens. In the global context of sustainability, food safety and environmental protection, such semiochemicals represent an alternative and promising approach to integrated pest management. PMID- 22305064 TI - Phenolic metabolites in carnivorous plants: Inter-specific comparison and physiological studies. AB - Despite intensive phytochemical research, data related to the accumulation of phenols in carnivorous plants include mainly qualitative reports. We have quantified phenolic metabolites in three species: Drosera capensis, Dionaea muscipula and Nepenthes anamensis in the "leaf" (assimilatory part) and the "trap" (digestive part). For comparison, commercial green tea was analysed. Phenylalanine ammonia-lyase (PAL) activities in Dionaea and Nepenthes were higher in the trap than in the leaf while the opposite was found in Drosera. Soluble phenols and majority of phenolic acids were mainly accumulated in the trap among species. Flavonoids were abundant in Drosera and Dionaea traps but not in Nepenthes. Phenolic acids were preferentially accumulated in a glycosidically bound form and gallic acid was the main metabolite. Green tea contained more soluble phenols and phenolic acids but less quercetin. In vitro experiments with Drosera spathulata revealed that nitrogen deficiency enhances PAL activity, accumulation of phenols and sugars while PAL inhibitor (2-aminoindane-2 phosphonic acid) depleted phenols and some amino acids (but free phenylalanine and sugars were elevated). Possible explanations in physiological, biochemical and ecological context are discussed. PMID- 22305065 TI - Molecular and physiological dissection of enhanced seed germination using short term low-concentration salt seed priming in tomato. AB - Seed germination is the initial step of plant development. Seed priming with salt promotes seed germination in tomato (Solanum lycopersicum L.); however, the molecular and physiological mechanisms underlying the enhancement of seed germination by priming remain to be elucidated. In this study, we examined the following in seeds both during and after priming treatment: the endogenous abscisic acid (ABA) and gibberellin (GA) concentrations; the expression of genes encoding ABA catabolic and GA biosynthesis enzymes, including 8'-hydroxylase (CYP707A), copalyl diphosphate synthase (CPS), GA 20-oxidase (GA20ox) and GA 3 oxidase (GA3ox); and endosperm cap weakening enzymes, including expansin (EXP), class I beta-1,3-glucanase (GulB), endo-beta-mannanase (MAN) and xyloglucan endotransglucosylase (XTH). Tomato seeds were soaked for 24 h at 25 degrees C in the dark in 300 mM NaCl (NaCl-priming) or distilled water (hydro-priming). For both priming treatments, the ABA content in the seeds increased during treatment but rapidly decreased after sowing. Both during and after the priming treatments, the ABA levels in the hydro-primed seeds and NaCl-primed seeds were not significantly different. The expression levels of SlGA20ox1, SlGA3ox1 and SlGA3ox2 were significantly enhanced in the NaCl-primed seeds compared to the hydro-primed seeds. The GA(4) content was quantifiable after both types of priming, indicating that GA(4) is the major bioactive GA molecule involved in tomato seed germination. The GA(4) content was significantly higher in the NaCl primed seeds than in the hydro-primed seeds 12 h after sowing and thereafter. Additionally, the peak expression levels of SlEXP4, SlGulB, SlMAN2 and SlXTH4 occurred earlier and were significantly higher in the NaCl-primed seeds than in the hydro-primed seeds. These results suggest that the observed effect of NaCl priming on tomato seed germination is caused by an increase of the GA(4) content via GA biosynthetic gene activation and a subsequent increase in the expression of genes related to endosperm cap weakening. PMID- 22305066 TI - Reactive oxygen species from chloroplasts contribute to 3-acetyl-5 isopropyltetramic acid-induced leaf necrosis of Arabidopsis thaliana. AB - 3-Acetyl-5-isopropyltetramic acid (3-AIPTA), a derivate of tetramic acid, is responsible for brown leaf-spot disease in many plants and often kills seedlings of both mono- and dicotyledonous plants. To further elucidate the mode of action of 3-AIPTA, during 3-AIPTA-induced cell necrosis, a series of experiments were performed to assess the role of reactive oxygen species (ROS) in this process. When Arabidopsis thaliana leaves were incubated with 3-AIPTA, photosystem II (PSII) electron transport beyond Q(A) (the primary plastoquinone acceptor of PSII) and the reduction of the end acceptors at the PSI acceptor side were inhibited; this was followed by increase in charge recombination and electron leakage to O(2), resulting in chloroplast-derived oxidative burst. Furthermore, the main antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) lost their activity. Excess ROS molecules directly attacked a variety of cellular components and subsequently caused electrolyte leakage, lipid peroxidation and cell membrane disruption. Finally, this led to cell destruction and leaf tissue necrosis. Thus, 3-AIPTA-triggered leaf necrosis of Arabidopsis was found to be a result of direct oxidative injury from the chloroplast-originated ROS burst initiated by the inhibition of normal photosynthetic electron transport. PMID- 22305067 TI - Phytohormones as regulators of heavy metal biosorption and toxicity in green alga Chlorella vulgaris (Chlorophyceae). AB - The present study was undertaken to test the influence of exogenously applied phytohormones: auxins (IAA, IBA, NAA, PAA), cytokinins (BA, CPPU, DPU, 2iP, Kin, TDZ, Z), gibberellin (GA(3)), jasmonic acid (JA) as well as polyamine - spermidine (Spd) upon the growth and metabolism of green microalga Chlorella vulgaris (Chlorophyceae) exposed to heavy metal (Cd, Cu, Pb) stress. The inhibitory effect of heavy metals on algal growth, metabolite accumulation and enzymatic as well as non-enzymatic antioxidant system was arranged in the following order: Cd > Pb > Cu. Exogenously applied phytohormones modify the phytotoxicity of heavy metals. Auxins, cytokinins, gibberellin and spermidine (Spd) can alleviate stress symptoms by inhibiting heavy metal biosorption, restoring algal growth and primary metabolite level. Moreover, these phytohormones and polyamine stimulate antioxidant enzymes' (superoxide dismutase, ascorbate peroxidase, catalase) activities and ascorbate as well as glutathione accumulation by producing increased antioxidant capacity in cells growing under abiotic stress. Increased activity of antioxidant enzymes reduced oxidative stress expressed by lipid peroxidation and hydrogen peroxide level. In contrast JA enhanced heavy metal toxicity leading to increase in metal biosorption and ROS generation. The decrease in cell number, chlorophylls, carotenoids, monosaccharides, soluble proteins, ascorbate and glutathione content as well as antioxidant enzyme activity was also obtained in response to JA and heavy metals. Determining the stress markers (lipid peroxidation, hydrogen peroxide) and antioxidants' level as well as antioxidant enzyme activity in cells is important for understanding the metal-specific mechanisms of toxicity and that these associated novel endpoints may be useful metrics for accurately predicting toxicity. The data suggest that phytohormones and polyamine play an important role in the C. vulgaris responding to abiotic stressor and algal adaptation ability to metal contamination of aquatic environment. PMID- 22305068 TI - Photosynthetic performance of Jatropha curcas fruits. AB - Jatropha curcas (L.) trees under north Indian conditions (Lucknow) produce fruits in two major flushes, once during autumn-winter (October-December). The leaves at this time are at the senescence stages and already shedding. The second flush of fruit setting occurs during the summer (April-June) after the leaves have formed during spring (March-April). Photosynthetic performance of detached jatropha fruits was studied at three developmental stages, immature, mature and ripe fruits. Studies were made in both winter and summer fruits in response to light, temperature and vapour pressure deficit (VPD) under controlled conditions to assess the influence of these environmental factors on the photosynthetic performance of jatropha fruits. Immature fruits showed high light saturating point of around 2000 MUmol m(-2) s(-1). High VPD did not show an adverse effect on the fruit A. Stomatal conductance (g(s)) showed an inverse behaviour to increasing VPD, however, transpiration (E) was not restricted by the increasing VPD in both seasons. During winter in absence of leaves on the jatropha tree the fruits along with the bark contributes maximum towards photoassimilation. Dark respiration rates (R(d)) monitored in fruit coat and seeds independently, showed maximum R(d) in seeds of mature fruit and these were about five times more than its fruit coat, reflecting the higher energy requirement of the developing fruit during maximum oil synthesis stage. Photosynthesis and fluorescence parameters studied indicate that young jatropha fruits are photosynthetically as efficient as its leaves and play a paramount role in scavenging the high concentration of CO(2) generated by the fruit during respiration. PMID- 22305069 TI - Protease inhibitor (PI) mediated defense in leaves and flowers of pigeonpea (protease inhibitor mediated defense in pigeonpea). AB - More than 200 insect pests are found growing on pigeonpea. Insects lay eggs, attack and feed on leaves, flowers and developing pods. Plants have developed elaborate defenses against these insect pests. The present work evaluates protease inhibitor (PI) based defense of pigeonpea in leaves and flowers. PIs in the extracts of these tender tissues were detected by using gel X-ray film contact print method. Up to three PIs (PI-3, PI-4 and PI-5) were detected in these tissues as against nine (PI-1-PI-9) in mature seeds. PI-3 is the major component of these tissues. Mechanical wounding, insect chewing, fungal pathogenesis and application of salicylic acid induced PIs in pigeonpea in these tissues. Induction was found to be local as well as systemic but local response was stronger than systemic response. During both local and systemic induction, PI 3 appeared first. In spite of the presence and induction of PIs in these tender tissues and seeds farmers continue to suffer yield loses. This is due to the weak expression of PIs. However the ability of the plant to respond to external stimuli by producing defense proteins does not seem to be compromised. This study therefore indicates that PIs are components of both constitutive and inducible defense and provide a ground for designing stronger inducible defense (PIs or other insect toxin based) in pigeonpea. PMID- 22305070 TI - Structure and properties of the potato chymotrypsin inhibitor. AB - The potato tubers contain proteins that inhibit serine proteinases and belong to subfamily of potato Kunitz-type proteinase inhibitors (PKPI). New highly purified protein had been isolated from mature potato tubers (Solanum tuberosum L., cv. Zukov's Jubilee). The protein is a single polypeptide chain of molecular, weighing 23 kDa. The 20 N-terminal amino acid residues of the protein were determined by automatic Edman procedure. On the basis of N-terminal sequence structure and the molecular mass it is indicated that the inhibitor is a potato Kunitz-type serine proteinase inhibitor that belongs to group B. It was denoted as PKCI (potato Kunitz-type chymotrypsin inhibitor). The PKCI was able to inhibit chymotrypsin and trypsin with the same degree of effectiveness. It formed equimolar complexes with both enzymes. The protein PKCI is a double-headed proteinase inhibitor and is able to bind simultaneously two molecules of different enzymes. The probable cDNA of the inhibitor, denoted as PKPIJ-B consists of a 579-bp open reading frame, encodes protein out of 193-amino acids with a signal peptide (10 residues), indicating that this protein is synthesized as a preprotein. Deduced amino acid sequence of the cDNA is aligned with the respective sequences of already known PKPI, belonging to group B. PMID- 22305071 TI - Uptake and incorporation of iron in sugar beet chloroplasts. AB - Chloroplasts contain 80-90% of iron taken up by plant cells. Though some iron transport-related envelope proteins were identified recently, the mechanism of iron uptake into chloroplasts remained unresolved. To shed more light on the process of chloroplast iron uptake, trials were performed with isolated intact chloroplasts of sugar beet (Beta vulgaris). Iron uptake was followed by measuring the iron content of chloroplasts in the form of ferrous-bathophenantroline disulphonate complex after solubilising the chloroplasts in reducing environment. Ferric citrate was preferred to ferrous citrate as substrate for chloroplasts. Strong dependency of ferric citrate uptake on photosynthetic electron transport activity suggests that ferric chelate reductase uses NADPH, and is localised in the inner envelope membrane. The K(m) for iron uptake from ferric-citrate pool was 14.65 +/- 3.13 MUM Fe((III))-citrate. The relatively fast incorporation of (57)Fe isotope into Fe-S clusters/heme, detected by Mossbauer spectroscopy, showed the efficiency of the biosynthetic machinery of these cofactors in isolated chloroplasts. The negative correlation between the chloroplast iron concentration and the rate of iron uptake refers to a strong feedback regulation of the uptake. PMID- 22305072 TI - Chromium-induced tropane alkaloid production and H6H gene expression in Atropa belladonna L. (Solanaceae) in vitro-propagated plantlets. AB - Hyoscyamine and scopolamine tropane alkaloids found in several solanaceous plants are anticholinergic drugs. Hyoscyamine 6beta-hydroxylase (H6H) catalyzes two consecutive oxidation reactions. The first reaction is the hydroxylation of hyoscyamine to 6beta-hydroxyhyoscyamine and the second is epoxidation of 6beta hydroxyhyoscyamine yielding scopolamine that is the final metabolite in the tropane alkaloid biosynthetic pathway. The effects of trivalent chromium as KCr (SO4)(2) on the production of tropane alkaloids and the expression of hyoscyamine 6beta-hydroxylase gene (h6h) were studied in micro-propagated Atropa belladonna L. plantlets. The results showed that chromium treatment decreased the growth parameters (weights and lengths of the plantlets) and chlorophyll contents and increased proline contents. Moreover, semiquantitave RT-PCR analysis showed that the transcript level of H6H increased under chromium treatment. This treatment also increased hyoscyamine and scopolamine contents as shown by HPLC analysis. Changes of scopolamine contents correlate with the expression levels of h6h gene under different concentrations of chromium. PMID- 22305073 TI - Purification and physicochemical characterization of a serine protease with fibrinolytic activity from latex of a medicinal herb Euphorbia hirta. AB - A 34 kDa serine protease, designated as hirtin, with fibrinolytic activity was purified to homogeneity from the latex of Euphorbia hirta by the combination of ion exchange and gel filtration chromatography. The N-terminal sequence of hirtin was found to be YAVYIGLILETAA/NNE. Hirtin exhibited esterase and amidase activities along with azocaseinolytic, gelatinolytic, fibrinogenolytic and fibrinolytic activities. It preferentially hydrolyzed Aalpha and alpha-chains, followed by Bbeta and beta, and gamma and gamma-gamma chains of fibrinogen and fibrin clot respectively. The optimum pH and temperature for enzyme activity was found to be pH 7.2 and 50 degrees C respectively. Enzymatic activity of hirtin was significantly inhibited by PMSF and AEBSF. It showed higher specificity for synthetic substrate p-tos-GPRNA for thrombin. The CD spectra of hirtin showed a high content of beta-sheets as compared to alpha-helix. The results indicate that hirtin is a thrombin-like serine protease and may have potential industrial and therapeutic applications. PMID- 22305074 TI - Expression of arabinogalactan proteins during tomato fruit ripening and in response to mechanical wounding, hypoxia and anoxia. AB - Arabinogalactan proteins (AGPs) are highly glycosylated members of the superfamily of hydroxyproline-rich glycoproteins (HRGPs). Despite their implication in many aspects of plant growth and development little is known about their role in tomato fruit ripening (Solanum lycopersicum) and their response to abiotic stress in tomato fruits. A search of the currently available tomato genome database resulted in the identification of 34 genes encoding putative AGPs, with at least 20 of them being expressed in fruit. We monitored the abundance of AGPs bound by JIM8 and JIM13 monoclonal antibodies as well as the gene expression profiles of the Lys-rich LeAGP1 and two classical AGPs, SlAGP2 and SlAGP4. The JIM8- and JIM13-bound AGPs showed constitutive expression during fruit ripening and under hypoxic conditions, slight up-regulation to mechanical wounding in excised tomato fruit pericarp discs and up-regulation under anoxia indicating functional roles for these proteins in the developmental program of ripening and in response to abiotic stresses. Moreover, the SlAGP2 mRNA was significantly up-regulated during fruit ripening following the climacteric ethylene production, a pattern of expression similar to that of tomato fruit PG. The SlAGP4 and LeAGP1 mRNAs were up-regulated in response to mechanical wounding while under anoxia only the SlAGP4 transcript was induced. The protein and mRNA levels of these AGPs were induced under mechanical wounding while only JIM8-bound AGPs and SIAGP4 expression were induced under anoxic conditions. Our results indicate that selected tomato AGPs seem to play a role in fruit ripening as well as in response to mechanical wounding and anoxia. PMID- 22305075 TI - Different peroxidase activities and expression of abiotic stress-related peroxidases in apical root segments of wheat genotypes with different drought stress tolerance under osmotic stress. AB - One-week-old seedlings of Triticum aestivum L. cv. Plainsman V, a drought tolerant; and Cappelle Desprez, a drought sensitive wheat cultivar were subjected gradually to osmotic stress using polyethylene glycol (PEG 6000) reaching 400 mOsm on the 11th day. Compared to controls cv. Plainsman V maintained the root growth and relative water content of root tissues, while these parameters were decreased in the drought sensitive cv. Cappelle Desprez under PEG-mediated osmotic stress. Simultaneously, H(2)O(2) content in 1-cm-long apical segment of roots comprising the proliferation and elongation zone, showed a transient increase in cv. Plainsman V and a permanent raise in cv. Cappelle Desprez. Measurements of the transcript levels of selected class III peroxidase (TaPrx) coding sequences revealed significant differences between the two cultivars on the 9th day, two days after applying 100 mOsm PEG. The abundance of TaPrx04 transcript was enhanced transitionally in the root apex of cv. Plainsman V but decreased in cv. Cappelle Desprez under osmotic stress while the expression of TaPrx01, TaPrx03, TaPrx19, TaPrx68, TaPrx107 and TaPrx109-C decreased to different extents in both cultivars. After a transient decrease, activities of soluble peroxidase fractions of crude protein extracts rose in both cultivars on day 11, but the activities of cell wall-bound fractions increased only in cv. Cappelle Desprez under osmotic stress. Parallel with high H(2)O(2) content of the tissues, certain isoenzymes of covalently bound fraction in cv. Cappelle Desprez showed increased activity suggesting that they may limit the extension of root cell walls in this cultivar. PMID- 22305076 TI - Purification and kinetic characterization of two peroxidases of Selaginella martensii Spring. involved in lignification. AB - Two cationic peroxidases from Selaginella martensii Spring. (SmaPrx2 and SmaPrx3) were purified using a three-step protocol which includes ammonium sulfate precipitation, adsorption chromatography on phenyl sepharose and cationic exchange chromatography on SP sepharose. The molecular mass for SmaPrx2 and SmaPrx3 was calculated to be 36.3 kDa and 45.6 kDa, respectively, according to MALDI-TOF/TOF. The isoelectric points were estimated in 9.2 and 9.5 for SmaPrx2 and SmaPrx3, respectively, according to isoelectrofocusing. Both enzymes show a typical peroxidase UV-visible spectrum with a Soret peak at 403 nm for SmaPrx2 and 404 nm for SmaPrx3. The specific activities showed against several substrates and the kinetic parameters suggest SmaPrx2 and SmaPrx3 have specific roles in cell wall formation and especially in lignin biosynthesis. Several peptides from tryptic digestion of both peroxidases were identified through MALDI-TOF MS/MS. The presence in these peptides of structural determinants typical of syringyl peroxidases indicates these proteins show no structural restrictions to oxidize syringyl moieties. These data, along with the in vitro capacity of using sinapyl alcohol as substrate and the low K(m) in the MUM range suggest these two peroxidases may be responsible for the oxidation of syringyl monolignols that leads to syringyl lignins biosynthesis. PMID- 22305077 TI - Susceptibility to downy mildew in grape clusters: New microscopical and biochemical insights. AB - Grape clusters of different Vitis genotypes, including Vitis vinifera cvs Chasselas and Merlot, and two interspecific grape varieties, Solaris (cvs. Merzling* x (Saperavi severneyi x Muscat ottonel)) and 2091 (cvs. Gamaret x Bronner), are susceptible or resistant to downy mildew. These cultivars were inoculated with Plasmopara viticola at three developmental stages (BBCH stages 53, 69 and 75). Samples were examined by scanning electron microscopy and the synthesis of stilbenes was measured. Microscopical examinations of pedicels, rachis and calyptras showed important differences in stomatal structures within seasonal development. At BBCH 53, successful infections were observed on all tested cultivars and functional stomata were present, while no infections were observed after this stage. At BBCH 69 and 75, cracks were observed around the stomata and guard cells were unstructured or completely collapsed, leading to closed-like stomata. At BBCH 53, significant stilbene accumulation was quantified in 2091 and Solaris; pterostilbene and delta-viniferin were produced in large amounts. In the susceptible varieties, only piceid and resveratrol were induced. At the other two stages, the concentration of all measured stilbenes was undetectable. The critical roles of seasonal development and stilbenes in the resistance of grape clusters towards downy mildew are discussed. PMID- 22305078 TI - Distress, defiance or adaptation? A review paper of at-risk mental health states in young offenders. AB - AIM: This paper firstly aims to explore the prevalence of mental health problems in young offenders and secondly, to review the factors which mean a young offender is at risk of developing more serious and chronic mental health problems, including psychosis. METHODS: The literature in this field will be reviewed, and the highlighted risk factors explored in detail. RESULTS: Reviewing the evidence base highlights the complex needs of this population, as the prevalence of mental health problems in both detained and community-based young offenders is high, with the presence of at least one mental health problem found in up to 92%. There is much data to suggest that young offenders have many of the risk indicators that would place them at risk of significant mental health problems according to previously identified criteria. Factors such as intellectual level, difficulties in school, substance abuse problems, exposure to trauma and problems understood within an attachment framework are explored. CONCLUSION: The main conclusion is that this population have many risk factors which increase the possibility of developing serious mental health problems, therefore highlighting the need for early intervention. PMID- 22305079 TI - Improvement in T-staging of rectal carcinoma: using a novel endorectal ultrasonography technique with sterile coupling gel filling the rectum. AB - Our purpose was to study the accuracy of using endorectal ultrasonography (ERUS) with sterile coupling gels filling the rectum in the preoperative T-staging of rectal carcinoma. A total of 189 patients with confirmed rectal carcinoma were recruited. All underwent ERUS and surgery within the week following sonography. EURS was performed by introducing sterile coupling gel into the rectum. Two radiologists looked at the images at the same time and agreed upon staging. Rectal carcinoma was staged from Tis to T4. The accuracy of T-staging by ERUS was 89.95%. The sensitivity, specificity, PPV and NPV for ERUS at different stages were calculated. For early stage (Tis and T1), these values were 93.62%, 97.89%, 93.62% and 97.89%, respectively. ERUS filling with sterile coupling gel in the rectum overcomes the pressure effect from a water bath and the restriction caused by tumor stenosis, thus, greatly improving the accuracy of T-staging. The examination is real-time, safe and inexpensive. PMID- 22305080 TI - Phytochemical analysis of a herbal tea from Artemisia annua L. AB - Strategies to control diffusion of malaria needs to account for the increase of resistance of the parasite to the conventional antimalarial drugs. It has been proposed that a traditional aqueous preparation from Artemisia annua, with a low content of the active compound, artemisinin, may reduce the risk of resistance of the protozoa and be relatively more effective in the treatment of the disease. The solubility properties of the molecule have been the matter of concern about the therapeutic usefulness of herbal teas from A. annua. The present study aimed at analysing the chemical profile of a tea infusion from A. annua. Tea from A. annua was prepared through infusion of the plant aerial parts in water for 1, 24 and 48 h. Content of artemisinin was determined by HPLC-ELSD. Overall chemical characterization of the extracts was carried out by a combination of metabolomic techniques. The artemisinin content varied only slightly in the three different extracts (about 0.12%). A series of mono-caffeoyl- and mono-feruloyl-quinic acids, di-caffeoyl- and di-feruloyl-quinic acids was identified as main components of the tea infusion, together with some flavonoids. Reconstitution of the same extracts in less polar or apolar solvents resulted in a different composition with no phenolics and a much lower concentration of artemisinin. PMID- 22305081 TI - Quantification of irinotecan, SN38, and SN38G in human and porcine plasma by ultra high-performance liquid chromatography-tandem mass spectrometry and its application to hepatic chemoembolization. AB - An analytical method was developed and validated for the quantitative determination of irinotecan, its active metabolite SN38, and glucuronidated SN38 (SN38-G) in both porcine and human plasma. Calibration curves were linear within the concentration range of 0.5-100 ng/mL for SN38 and SN38-G, and 5-1000 ng/mL for irinotecan. Sample pretreatment involved solid-phase extraction of 0.1 mL aliquots of plasma. Irinotecan, SN38, SN38-G, and the internal standards, irinotecan-d10, tolbutamide, and camptothecin, respectively, were separated on a Waters ACQUITY UPLC BEH RP18 column (2. 1mm * 50 mm, 1.7 MUm), using a mobile phase composed of methanol and 0.1% formic acid. Accuracy of quality control samples in human plasma ranged from 98.5 to 110.3%, 99.5 to 101.7% and 96.2 to 98.9% for irinotecan, SN38, and SN38-G, respectively. Precision of the three analytes in the same order ranged from 0.8 to 2.8%, 2.4 to 5.7%, and 2.4 to 2.8%. All three analytes proved stable in plasma through four freeze/thaw cycles, as well as through 6h in whole blood at room temperature. The method was likewise validated in porcine plasma with comparable accuracies and precisions also within the generally acceptable range. The validated method was applied to both preclinical and clinical trials involving hepatic chemoembolization of irinotecan drug-eluting beads to study the pharmacokinetics of the three analytes. PMID- 22305082 TI - Determination of trovafloxacin and marbofloxacin in sheep plasma samples by HPLC using UV detection. AB - A simple and rapid high performance liquid chromatographic method was developed, validated and applied for the simultaneous determination of marbofloxacin (MBX) and trovafloxacin (TVX) in sheep plasma. Samples were extracted with 20% perchloric acid and MBX and TVX were separated on a C(18) column using a gradient mobile phase system consisting of 17.5mM of NaH(2)PO(4) and 1.5mM of tetrabutylammonium hydroxide aqueous solution, pH 3 (A) and 50% acetonitrile and 50% methanol (B), with UV detection at 293 and 270 nm. The retention times of MBX and TVX were 4.9 and 6.6 min respectively. The detection and quantification limits for MBX and TVX were 2 ng/mL and 10 ng/mL respectively for both compounds. The calibration curves were linear over a concentration range of 10-50,000 ng/mL for both antibiotics. The linearity, precision, accuracy, recovery and stability of the assay were evaluated from spiked sheep plasma. The method was successfully applied to sheep plasma samples obtained from MBX and TVX pharmacokinetic studies. PMID- 22305083 TI - Pharmaceutical and biomedical applications of affinity chromatography: recent trends and developments. AB - Affinity chromatography is a separation technique that has become increasingly important in work with biological samples and pharmaceutical agents. This method is based on the use of a biologically related agent as a stationary phase to selectively retain analytes or to study biological interactions. This review discusses the basic principles behind affinity chromatography and examines recent developments that have occurred in the use of this method for biomedical and pharmaceutical analysis. Techniques based on traditional affinity supports are discussed, but an emphasis is placed on methods in which affinity columns are used as part of HPLC systems or in combination with other analytical methods. General formats for affinity chromatography that are considered include step elution schemes, weak affinity chromatography, affinity extraction and affinity depletion. Specific separation techniques that are examined include lectin affinity chromatography, boronate affinity chromatography, immunoaffinity chromatography, and immobilized metal ion affinity chromatography. Approaches for the study of biological interactions by affinity chromatography are also presented, such as the measurement of equilibrium constants, rate constants, or competition and displacement effects. In addition, related developments in the use of immobilized enzyme reactors, molecularly imprinted polymers, dye ligands and aptamers are briefly considered. PMID- 22305084 TI - Development of a HPLC/MS/MS method for simultaneous determination of tinidazole, dyclonine and chlorhexidine in rat plasma and its application in the pharmacokinetic research of a film-forming solution. AB - A rapid and sensitive HPLC/MS/MS method was developed and validated for simultaneous determination of tinidazole, dyclonine and chlorhexidine, the three main components of a film-forming solution, in rat plasma. The plasma samples were pretreated by solid phase extraction (SPE) method. Separation was achieved on a Phenomenex Gemini C(18) column (50 mm * 2.0 mm, 5 MUm) using an isocratic mobile phase system composed of methanol-ammonium formate (10 mM)-formic acid (56:44:0.2, v/v/v) (pH 3.5) at a flow rate of 0.2 mL/min. Analytes were determined by tandem mass spectrometry with electrospray positive ionization and multiple-reaction monitoring (MRM) mode. The monitoring ions were (m/z) 247.4 -> (m/z) 81.9 for tinidazole, (m/z) 290.1 -> (m/z) 97.8 for dyclonine, (m/z) 505.0 > (m/z) 335.3 for chlorhexidine and (m/z) 282.1 -> (m/z) 212.0 for phentolamine (internal standard). The calibration curves were linear in the range of 2-1000 ng/mL for the three components. The precision and accuracy of the method were well within the generally accepted criteria for biomedical analysis. It has been successfully applied to the pharmacokinetic research of a film-forming solution in rat. PMID- 22305085 TI - [Relationship between Castleman's disease and non-Hodgkin lymphoma]. PMID- 22305087 TI - [English fathoms Archives de Pediatrie]. PMID- 22305086 TI - Hepatitis B virus in transfusion medicine: still a problem? AB - Hepatitis B virus (HBV) has probably evolved with humans for nearly 35,000 years. HBV diversified into 9 genotypes (A-I) presenting specific features directing epidemiology, clinical expression and testing. Genotypes E and C are more infectious and carry higher risk of chronicity and cancer. HBsAg blood screening implemented 40 years ago enormously decreased the risk of transfusion transmission but the remaining risk requires extremely sensitive nucleic acid testing (NAT) to be removed. Limitations of the host immune system, the impact of immunodeficiency and the mechanisms utilised for viral persistence were recently identified. HBV replication produces excess HBsAg and infectious and defective viral particles but screening assays for HBsAg or viral particles alone do not allow fully efficient detection, making necessary screening for both. The host immune system fails to completely control the virus that escapes and persists unrecognized at very low levels or as immuno-selected variants. Variants may not be identified by assays, explaining false negative results. Specific mutations may affect post-transcriptional mechanisms including HBV RNA splicing. Asymptomatic HBV infected blood donors are at risk of long-term complications through mechanisms to be understood for appropriate counselling. Infectivity of occult HBV infection (OBI) by transfusion appears low, anti-HBc (anti-core antigen) only being more infectious than anti-HBs (anti-S protein) positive units. PMID- 22305088 TI - [Development of a screening scale for children at risk of baby bottle tooth decay]. AB - OBJECTIVE: Baby bottle tooth decay is a severe form of early childhood caries. This study aims to elaborate a screening tool for at risk children in order to facilitate primary prevention. METHODS: A case-control study was conducted among children suffering from baby bottle tooth decay and children with no dental caries. Cases were children aged 5 years or less at diagnosis who experienced at least four caries with one or more affecting maxillary incisors. Controls were children matched for age and sex. Parents were interviewed by phone about their child's exposure to potential risk factors. RESULTS: We included 88 children suffering from baby bottle tooth decay and 88 children with no dental caries. In multivariate analysis, low social class (OR 6.39 [95% CI, 1.45-28.11]), prolonged bottle feeding or bedtime feeding (OR 153.2 [95% CI, 11.77-1994.96]), and snacking (OR 5.94 [95% CI, 1.35-26.2]) were significantly associated with baby bottle tooth decay. Regular dental visits were a significant protecting factor (OR 0.13 [95% CI, 0.02-0.77]). A score was developed using these significant risk factors and tested on the survey population. The mean score was 13/20 for cases and 4/20 for controls. DISCUSSION: These results are in accordance with the literature, except for brushing teeth, which was not significantly associated with baby bottle tooth decay in our study. CONCLUSION: A screening scale with a score of 20 points was proposed. Future validation is required. Pediatricians and general practitioners should encourage parents to change their habits. PMID- 22305089 TI - [Liver torsion leading to death in a 16-month-old infant treated neonatally for an omphalocele]. AB - We report the case of an infant who underwent surgery on the first day of life for a giant omphalocele. At the age of 16 months, he presented an acute abdominal syndrome and died a few hours later. Autopsy revealed a twisted left liver lobe (LL) including a suprahepatic vein. To our knowledge, this is the first case of giant omphalocele complicated by twisted liver lobe and fatal outcome. PMID- 22305091 TI - Phage therapy pharmacology phage cocktails. AB - Phage therapy is the clinical or veterinary application of bacterial viruses (bacteriophages) as antibacterial "drugs." More generally, phages can be used as biocontrol agents against plant as well as foodborne pathogens. In this chapter, we consider the therapeutic use of phage cocktails, which is the combining of two or more phage types to produce more pharmacologically diverse formulations. The primary motivation for the use of cocktails is their broader spectra of activity in comparison to individual phage isolates: they can impact either more bacterial types or achieve effectiveness under a greater diversity of conditions. The combining of phages can also facilitate better targeting of multiple strains making up individual bacterial species or covering multiple species that might be responsible for similar disease states, in general providing, relative to individual phage isolates, a greater potential for presumptive or empirical treatment. Contrasting the use of phage banks, or even phage isolation against specific etiologies that have been obtained directly from patients under treatment, here we consider the utility as well as potential shortcomings associated with the use of phage cocktails as therapeutic antibacterial agents. PMID- 22305090 TI - Lack of decline in childhood malaria, Malawi, 2001-2010. AB - In some areas of Africa, health facility data have indicated declines in malaria that might have resulted from increasingly effective control programs. Most such reports have been from countries where malaria transmission is highly seasonal or of modest intensity. In Malawi, perennial malaria transmission is intense, and malaria control measures have been scaled up during the past decade. We examined health facility data for children seen as outpatients and parasitemia-positive children hospitalized with cerebral malaria in a large national hospital. The proportion of Plasmodium falciparum-positive slides among febrile children at the hospital declined early in the decade, but no further reductions were observed after 2005. The number of admissions for cerebral malaria did not differ significantly by year. Continued surveillance for malaria is needed to evaluate the effects of the increased malaria control efforts. PMID- 22305092 TI - Utility of Greater Wax Moth Larva (Galleria mellonella) for Evaluating the Toxicity and Efficacy of New Antimicrobial Agents. AB - There is an urgent need for new antimicrobial agents to combat infections caused by drug-resistant pathogens. Once a compound is shown to be effective in vitro, it is necessary to evaluate its efficacy in an animal infection model. Typically, this is achieved using a mammalian model, but such experiments are costly, time consuming, and require full ethical consideration. Hence, cheaper and ethically more acceptable invertebrate models of infection have been introduced, including the larvae of the greater wax moth Galleria mellonella. Invertebrates have an immune system that is functionally similar to the innate immune system of mammals, and often identical virulence and pathogenicity factors are used by human pathogenic microbes to infect wax moth larvae and mammals. Moreover, the virulence of many human pathogens is comparable in wax moth larvae and mammals. Using key examples from the literature, this chapter highlights the benefits of using the wax moth larva model to provide a rapid, inexpensive, and reliable evaluation of the toxicity and efficacy of new antimicrobial agents in vivo and prior to the use of more expensive mammalian models. This simple insect model can bridge the gap between in vitro studies and mammalian experimentation by screening out compounds with a low likelihood of success, while providing greater justification for further studies in mammalian systems. Thus, broader implementation of the wax moth larva model into anti-infective drug discovery and development programs could reduce the use of mammals during preclinical assessments and the overall cost of drug development. PMID- 22305093 TI - Bacteriophages and nanostructured materials. AB - Although people taking different approaches in the field of nanotechnology may target different size ranges, broadly, nanotechnology has the goal of creating structures in the 1-100 nm size range. This is the same size range that bacteriophages synthesize capsids. Bacteriophages also have the desirable property of self-fabrication or self-assembly--much of capsid structural assembly information is a function of the capsid proteins themselves rather than requiring other proteins. This would seem to make bacteriophage protein-based materials ideal for some nanotechnology applications. So far, the majority of research has taken one of two approaches: first, using filamentous bacteriophage display techniques to identify inorganic nanocrystal-binding peptides and using those peptides and the filamentous phage virions to create novel materials, and second, using a variety of bacteriophage and bacteriophage receptor-binding proteins to functionalize surfaces to create biosensors for bacterial detection. Here, I review these two approaches and speculate on some of the challenges for further development of bacteriophage protein-based self-assembling nanomaterials. PMID- 22305094 TI - Microbial communities associated with house dust. AB - House dust is a complex mixture of inorganic and organic material with microbes in abundance. Few microbial species are actually able to grow and proliferate in dust and only if enough moisture is provided. Hence, most of the microbial content originates from sources other than the dust itself. The most important sources of microbes in house dust are outdoor air and other outdoor material tracked into the buildings, occupants of the buildings including pets and microbial growth on moist construction materials. Based on numerous cultivation studies, Penicillium, Aspergillus, Cladosporium, and about 20 other fungal genera are the most commonly isolated genera from house dust. The cultivable bacterial flora is dominated by Gram-positive genera, such as Staplylococcus, Corynebacterium, and Lactococcus. Culture-independent studies have shown that both the fungal and the bacterial flora are far more diverse, with estimates of up to 500-1000 different species being present in house dust. Concentrations of microbes in house dust vary from nondetectable to 10(9) cells g(-1) dust, depending on the dust type, detection method, type of the indoor environment and season, among other factors. Microbial assemblages in different house dust types usually share the same core species; however, alterations in the composition are caused by differing sources of microbes for different dust types. For example, mattress dust is dominated by species originating from the user of the mattress, whereas floor dust reflects rather outdoor sources. Farming homes contain higher microbial load than urban homes and according to a recent study, temperate climate zones show higher dust microbial diversity than tropical zones. PMID- 22305095 TI - Serpula lacrymans, Wood and Buildings. AB - Serpula lacrymans, the causative agent of dry rot timber decay in buildings, is a Basidiomycete fungus in the Boletales clade. It owes its destructiveness to a uniquely well-developed capacity to colonize by rapid mycelial spread from sites of initial spore infection, coupled with aggressive degradation of wood cellulose. Genomic methods have recently elucidated the evolution and enzymic repertoire of the fungus, suggesting that it has a distinctive mode of brown rot wood decay. Using novel methods to image nutrient translocation, its mycelium has been modeled as a highly responsive resource-supply network. Dry rot is preventable by keeping timber dry. However, in established outbreaks, further mycelial spread can be arrested by inhibitors of translocation. PMID- 22305096 TI - Commentary on: Does empirical treatment of community-acquired pneumonia with fluoroquinolones delay tuberculosis treatment and result in fluoroquinolone resistance in Mycobacterium tuberculosis? Controversies and solutions. PMID- 22305097 TI - A population-based survey of the prevalence and types of glaucoma in Nepal: the Bhaktapur Glaucoma Study. AB - OBJECTIVE: To determine the prevalence and types of glaucoma in a Nepalese population. DESIGN: Cross-sectional, population-based survey. PARTICIPANTS: A total of 4800 subjects aged 40 years or older from the Bhaktapur district of Kathmandu valley. METHODS: Subjects aged 40 years or older were selected using a cluster sampling procedure and door-to-door enumeration for a population-based, cross-sectional study. All subjects underwent a detailed ocular examination at the base hospital, which included logarithm of minimal angle of resolution visual acuity, refraction, applanation tonometry, gonioscopy, Lens Opacities Classification System II cataract grading, retinal examination, and Swedish Interactive Thresholding Algorithm standard perimetry when indicated. MAIN OUTCOME MEASURES: Diagnosis of glaucoma was based on criteria described by the International Society for Geographic and Epidemiological Ophthalmology. RESULTS: A total of 4003 subjects underwent a comprehensive eye examination (response rate 83.4%), and complete data were available in 3991 subjects. The mean intraocular pressure was 13.3 mmHg (97.5th and 99.5th percentiles, 18 and 20 mmHg, respectively), and the mean vertical cup-to-disc ratio was 0.26 (97.5th and 99.5th percentiles, 0.6 and 0.8 mmHg, respectively). There were 75 subjects with glaucoma, an age- and sex-standardized prevalence of 1.80 (95% confidence interval [CI], 1.68-1.92). Age- and sex-standardized prevalence was 1.24% (95% CI, 1.14-1.34) for primary open-angle glaucoma (POAG), 0.39% (95% CI, 0.34-0.45) for primary angle-closure glaucoma (PACG), and 0.15% (95% CI, 0.07-0.36) for secondary glaucoma. The prevalence of glaucoma increased with an increase in age with no significant difference in gender. Primary angle-closure glaucoma was 3 times more common in women. Nine eyes were blind, and 2 subjects were bilaterally blind from glaucoma. CONCLUSIONS: The overall prevalence of glaucoma was 1.9%. Of all glaucoma cases, POAG accounted for 68%, PACG accounted for 22.67%, and secondary glaucoma accounted for 9.33%. Among the subjects with POAG, 96.08% had not been previously diagnosed. PMID- 22305098 TI - Pre-operative skin preparation practices: results of the 2007 French national assessment. AB - BACKGROUND: Pre-operative skin preparation, aimed at reducing the endogenous microbial flora, is one of the main preventive measures employed to decrease the likelihood of surgical site infection. National recommendations on pre-operative management of infection risks were issued in France in 2004. AIM: To assess compliance with the French national guidelines for pre-operative skin preparation in 2007. METHODS: A prospective audit was undertaken in French hospitals through interviews with patients and staff, and observation of professional practice. Compliance with five major criteria selected from the guidelines was studied: patient information, pre-operative showering, pre-operative hair removal, surgical site disinfection and documentation of these procedures. FINDINGS: Data for 41,188 patients from all specialties at 609 facilities were analysed. Patients were issued with information about pre-operative showering in 88.2% of cases [95% confidence interval (CI) 87.9-88.5]. The recommended procedure for pre operative showering, including hairwashing, with an antiseptic skin wash solution was followed by 70.3% of patients (95% CI 69.9-70.8); this percentage was higher when patients had received appropriate information (P < 0.001). Compliance with hair removal procedures was observed in 91.5% of cases (95% CI 91.2-91.8), and compliance with surgical site disinfection recommendations was observed in 25,529 cases (62.0%, 95% CI 61.5-62.5). The following documentary evidence was found: information given to patient, 35.6% of cases; pre-operative surgical hygiene, 82.3% of cases; and pre-operative site disinfection, 71.7% of cases. CONCLUSION: The essential content of the French guidelines seems to be understood, but reminders need to be issued. Some recommendations may need to be adapted for certain specialties. PMID- 22305099 TI - Delivering the infection control message: a communication challenge. AB - BACKGROUND: Hospital infection control teams (ICTs) worldwide face a constant challenge to deliver timely information to audiences with specific and diverse information needs. AIM: Our study investigated the communication flow between the ICT and healthcare workers (HCWs) at St Luke's Hospital, Malta, using an exploratory descriptive research design. METHOD: Using a self-administered questionnaire, data were collected from a stratified random sample of nurses (N = 143) and doctors (N = 63) working within inpatient wards; a response rate of 97% was achieved. FINDINGS: HCWs felt most comfortable receiving information from members of their same profession. Information transfer was mainly vertically up and down the hierarchy. Respondents preferred to receive information through educational activities (35%, N = 69) and through face-to-face contact (31%, N = 62). Electronic channels (e-mail and intranet) were ranked least preferable; however, only 41% (N = 81) had regular access to a computer system at work. The majority of respondents 91% (N = 181) trusted the information by the ICT and 60% (N = 118) regarded it as being consistent. Nevertheless, this did not guarantee constant compliance; 54% (N = 106) of respondents implemented IC measures only when they perceived a risk for their health. Greater presence of the ICT on the wards was recommended. CONCLUSION: Notwithstanding the electronic age, the study confirms that face-to-face contact between ICTs and HCWs remains the most effective way of disseminating IC information. PMID- 22305100 TI - Healthcare-associated infection in Irish long-term care facilities: results from the First National Prevalence Study. AB - BACKGROUND: Prevalence of healthcare-associated infection (HCAI) and antimicrobial use in Irish long-term care facilities (LTCFs) has never been studied. AIM: To collect baseline data on HCAI prevalence and antibiotic use in Irish LTCFs to inform national LTCF policy and plan future HCAI prevention programmes. METHODS: A prevalence study of HCAI and antibiotic use was undertaken in Irish LTCFs. Participation was voluntary. Data on HCAI risk factors, signs and symptoms of infection and antimicrobial use were collected prospectively on a single day in each institution. FINDINGS: Sixty-nine Irish LTCFs participated and 4170 eligible residents were surveyed; 472 (11.3%) had signs/symptoms of infection (266, 6.4%) and/or were on antibiotics (426, 10.2%). A third of residents (1430, 34.3%) were aged >=85 years and more than half disorientated (2110, 50.6%) with impaired mobility (2101, 50.4%). HCAI prevalence was 3.7% (range: 0-22.2%). The most common HCAI was urinary tract infection (UTI) (62 residents, 40% of HCAI). Presence of a urinary catheter was associated with UTI (P < 0.0000001). Antibiotics were prescribed for treatment (262 residents, 57.8%) and prophylaxis (182 residents, 40.2%) of infection. The most common indication for prophylaxis was UTI prevention (35.8% of total prescriptions). Fourteen (10.2%) residents on UTI prophylaxis had a urinary catheter. The most common indications for therapy included respiratory tract infections (35.1%), UTI (32.1%) and skin infection (21.8%). CONCLUSION: This study highlights the frequency of prophylactic antimicrobial prescribing and provides an important baseline to inform future preventive strategies. PMID- 22305101 TI - Baylisascaris procyonis infection in elderly person, British Columbia, Canada. PMID- 22305102 TI - Growth differentiation factor 3 is induced by bone morphogenetic protein 6 (BMP 6) and BMP-7 and increases luteinizing hormone receptor messenger RNA expression in human granulosa cells. AB - OBJECTIVE: To examine the relevance of growth differentiation factor 3 (GDF-3) and bone morphogenetic protein (BMP) cytokines in human ovary. DESIGN: Molecular studies. SETTING: Research laboratory. PATIENT(S): Eight women undergoing salpingo-oophorectomy and 30 women undergoing ovarian stimulation for in vitro fertilization. INTERVENTION(S): Localizing GDF-3 protein in human ovaries; granulosa cells (GC) cultured with GDF-3, BMP-6, or BMP-7 followed by RNA extraction. MAIN OUTCOME MEASURE(S): The localization of GDF-3 protein in normal human ovaries via immunohistochemical analysis, GDF-3 messenger RNA (mRNA) expression evaluation via quantitative real-time reverse transcription and polymerase chain reaction (RT-PCR), and evaluation of the effect of GDF-3 on leuteinizing hormone (LH) receptor mRNA expression via quantitative real-time RT PCR. RESULT(S): In the ovary, BMP cytokines, of the transforming growth factor beta (TGF-beta) superfamily, are known as a luteinization inhibitor by suppressing LH receptor expression in GC. Growth differentiation factor 3, a TGF beta superfamily cytokine, is recognized as an inhibitor of BMP cytokines in other cells. Immunohistochemical analysis showed that GDF-3 was strongly detected in the GC of antral follicles. An in vitro assay revealed that BMP-6 or BMP-7 induced GDF-3 mRNA in GC. Also, GDF-3 increased LH receptor mRNA expression and inhibited the effect of BMP-7, which suppressed the LH receptor mRNA expression in GC. CONCLUSION(S): GDF-3, induced with BMP-6 and BMP-7, might play a role in folliculogenesis by inhibiting the effect of BMP cytokines. PMID- 22305103 TI - Comprehensive chromosome screening is highly predictive of the reproductive potential of human embryos: a prospective, blinded, nonselection study. AB - OBJECTIVE: To determine both the negative and positive predictive values of comprehensive chromosome screening (CCS) results for clinical outcome. DESIGN: Data obtained from two prospective, double-blinded, nonselection studies. SETTING: Academic center for reproductive medicine. PATIENT(S): One hundred forty six couples with a mean maternal age of 34.0 +/- 4.4 years and a mean paternal age of 37.3 +/- 5.8 years. INTERVENTION(S): Embryo biopsy for DNA fingerprinting and aneuploidy assessment. MAIN OUTCOME MEASURE(S): Failure rate of embryos predicted aneuploid by CCS (negative predictive value) and success rate of embryos predicted euploid by CCS (positive predictive value). RESULT(S): A total of 255 IVF-derived human embryos were cultured and selected for transfer without influence from CCS analysis. Embryos were biopsied before transfer, including 113 blastomeres at the cleavage stage and 142 trophectoderm biopsies at the blastocyst stage. Comprehensive chromosome screening was highly predictive of clinical outcome, with 96% of aneuploid predicted embryos failing to sustain implantation and 41% sustained implantation from embryos predicted to be euploid. CONCLUSION(S): These nonselection data provide the first prospective, blinded, clinical study directly measuring the predictive value of aneuploidy screening for clinical outcome. The clinical error rate of an aneuploidy designation is very low (4%), whereas implantation and delivery rates of euploid embryos are increased relative to the entire cohort of transferred embryos. PMID- 22305104 TI - A rat decellularized small bowel scaffold that preserves villus-crypt architecture for intestinal regeneration. AB - Management of intestinal failure remains a clinical challenge and total parenteral nutrition, intestinal elongation and/or transplantation are partial solutions. In this study, using a detergent-enzymatic treatment (DET), we optimize in rats a new protocol that creates a natural intestinal scaffold, as a base for developing functional intestinal tissue. After 1 cycle of DET, histological examination and SEM and TEM analyses showed removal of cellular elements with preservation of the native architecture and connective tissue components. Maintenance of biomechanical, adhesion and angiogenic properties were also demonstrated strengthen the idea that matrices obtained using DET may represent a valid support for intestinal regeneration. PMID- 22305105 TI - Wearing a safety harness during treadmill walking influences lower extremity kinematics mainly through changes in ankle regularity and local stability. AB - BACKGROUND: Wearing a harness during treadmill walking ensures the subject's safety and is common practice in biomedical engineering research. However, the extent to which such practice influences gait is unknown. This study investigated harness-related changes in gait patterns, as evaluated from lower extremity kinematics during treadmill walking. FINDINGS: Healthy subjects (n = 10) walked on a treadmill at their preferred speed for 3 minutes with and without wearing a harness (LiteGait(r), Mobility Research, Inc.). In the former condition, no weight support was provided to the subjects. Lower extremity kinematics was assessed in the sagittal plane from the mean (meanRoM), standard deviation (SDRoM) and coefficient of variation (CoVRoM) of the hip, knee, and ankle ranges of motion (RoM), as well as from the sample entropy (SampEn) and the largest Lyapunov exponent (LyE) of the joints' angles. Wearing the harness increased the meanRoM of the hip, the SDRoM and the CoVRoM of the knee, and the SampEn and the LyE of the ankle. In particular, the harness effect sizes for both the SampEn and the LyE of the ankle were large, likely reflecting a meaningful decline in the neuromuscular stabilizing control of this joint. CONCLUSIONS: Wearing a harness during treadmill walking marginally influences lower extremity kinematics, resulting in more or less subtle changes in certain kinematic variables. However, in cases where differences in gait patterns would be expressed through modifications in these variables, having subjects walk with a harness may mask or reinforce such differences. PMID- 22305106 TI - The vibration discomfort of standing people: relative importance of fore-and-aft, lateral, and vertical vibration. AB - Few studies have compared the discomfort caused by vibration in different directions, and few have investigated the vibration discomfort of standing people. This study was designed to compare the discomfort experienced by standing people exposed to sinusoidal vibration in the fore-and-aft, lateral, and vertical directions. Using the method of magnitude estimation, 12 subjects estimated the discomfort caused by 4-Hz sinusoidal vibration at 10 different magnitudes. At 4 Hz, subjects were less sensitive to lateral vibration than to fore-and-aft vibration (K(y)/K(x) = 0.71), and more sensitive to vertical vibration than to horizontal vibration (K(z)/K(x) = 1.95; K(z)/K(y) = 2.77). Previous findings showing how the discomfort of standing people depends on the frequency of fore and-aft, lateral, and vertical vibration were used to define frequency weightings that reflect relative sensitivity to vibration in each direction. The frequency weightings differ from those appropriate for seated people, and differ from the weightings for standing people in current standards that were mostly derived from understanding of the discomfort of seated people. PMID- 22305107 TI - Effects of ultrasound on growth, bioconversion of isoflavones and probiotic properties of parent and subsequent passages of Lactobacillus fermentum BT 8633 in biotin-supplemented soymilk. AB - This study aimed to evaluate the effects of ultrasound on Lactobacillus fermentum BT 8633 in parent and subsequent passages based on their growth and isoflavone bioconversion activities in biotin-supplemented soymilk. The treated cells were also assessed for impact of ultrasound on probiotic properties. The growth of ultrasonicated parent cells increased (P<0.05) by 3.23-9.14% compared to that of the control during fermentation in biotin-soymilk. This was also associated with enhanced intracellular and extracellular (8.4-17.0% and 16.7-49.2%, respectively; P<0.05) beta-glucosidase specific activity, leading to increased bioconversion of isoflavones glucosides to aglycones during fermentation in biotin-soymilk compared to that of the control (P<0.05). Such traits may be credited to the reversible permeabilized membrane of ultrasonicated parent cells that have facilitated the transport of molecules across the membrane. The growing characteristics of first, second and third passage of treated cells in biotin soymilk were similar (P>0.05) to that of the control, where their growth, enzyme and isoflavone bioconversion activities (P>0.05) were comparable. This may be attributed to the temporary permeabilization in the membrane of treated cells. Ultrasound affected probiotic properties of parent L. fermentum, by reducing tolerance ability towards acid (pH 2) and bile; lowering inhibitory activities against selected pathogens and reducing adhesion ability compared to that of the control (P<0.05). The first, second and third passage of treated cells did not exhibit such traits, with the exception of their bile tolerance ability which was inherited to the first passage (P<0.05). Our results suggested that ultrasound could be used to increase bioactivity of biotin-soymilk via fermentation by probiotic L. fermentum FTDC 8633 for the development of functional food. PMID- 22305108 TI - Socioeconomic disparities in the uptake of breast and cervical cancer screening in Italy: a cross sectional study. AB - BACKGROUND: Breast and cervical cancer screening are widely recognized as effective preventive procedures in reducing cancer mortality. The aim of this study was to evaluate the impact of socioeconomic disparities in the uptake of female screening in Italy, with a specific focus on different types of screening programs. METHODS: A cross-sectional study was conducted using data from the 2004 2005 national health interview survey. A sample of 15, 486 women aged 50-69 years for mammography and one of 35, 349 women aged 25-64 years for Pap smear were analysed. Logistic regression models were used to estimate the association between socioeconomic factors and female screening utilization. RESULTS: Education and occupation were positively associated with attendance to both screening. Women with higher levels of education were more likely to have a mammogram than those with a lower level (OR = 1.28; 95% CI = 1.10-1.49). Women of intermediate and high occupational classes were more likely to use breast cancer screening (OR = 1.77; 95% CI = 1.55-2.03, OR = 1.63; 95% CI = 1.40-1.91) compared to unemployed women. Women in the highest occupational class had a higher likelihood of cervical cancer screening compared to those in the lowest class (OR = 1.81; 95% CI = 1.63-2.01). Among women who attended screening, those with lower levels of education and lower occupational classes were more likely than more advantaged women to attend organized screening programs rather than being screened on the basis of their own initiative. CONCLUSIONS: Inequalities in the uptake of female screening widely exist in Italy. Organized screening programs may have an important role in increasing screening attendance and tackling inequalities. PMID- 22305109 TI - Dysfunctional forward model mechanisms and aberrant sense of agency in obsessive compulsive disorder. AB - BACKGROUND: Patients with obsessive-compulsive disorder (OCD) often lack the experience of action completion and have altered feelings of agency. This might depend on the integrity of predictions of action outcomes generated by forward models of the motor system. Such motor predictions are critical for inhibitory gating of actions and their consequences. Therefore, it was hypothesized that OCD patients show compromised forward model mechanisms. METHODS: To test whether inhibitory gating based on motor predictions is altered in OCD, we used electroencephalography to measure suppression of the N1 component of the event related potential during active generation and passive observation of visual feedback in 18 OCD patients and 18 healthy control subjects. Predictability of action feedback was manipulated on the basis of action and external cues, and simultaneous agency judgments were assessed. RESULTS: OCD patients showed significantly reduced N1 suppression to actively generated feedback as compared with passively observed feedback. Moreover, in OCD patients, the N1 was not modulated by additional predictive motor cues as observed in control subjects. Patients also reported enhanced estimations of agency experience, which correlated with the strength of incompleteness feelings. CONCLUSIONS: OCD patients fail to predict and suppress the sensory consequences of their own actions. The increased mismatch between expected and actual outcomes caused by this forward model dysfunction may explain persistent feelings of incompleteness even after properly executed actions and the augmented search for control in these patients. PMID- 22305110 TI - Tension-free vaginal tape for the treatment of urodynamic stress incontinence: efficacy and adverse effects at 10-year follow-up. AB - BACKGROUND: One of the most effective and popular current procedures for the surgical treatment of stress urinary incontinence (SUI) is tension-free midurethral slings. OBJECTIVE: To evaluate the outcomes of women with retropubic tension-free vaginal tape (TVT) for urodynamic stress incontinence (USI) after 10 yr follow-up. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective observational study. Consecutive women with proven USI were treated with TVT. Patients with mixed incontinence and/or anatomic evidence of pelvic organ prolapse were excluded. INTERVENTION: Standard retropubic TVT. MEASUREMENTS: Patients underwent preoperative clinical and urodynamic evaluations. During follow-up examinations, women were assessed for subjective satisfaction and objective cure rates. Multivariable analyses were performed to investigate outcomes. RESULTS AND LIMITATIONS: A total of 63 women were included. After 10 yr, 5 patients (8%) were lost or no longer evaluable. The 10-yr subjective, objective, and urodynamic cure rates were 89.7%, 93.1%, and 91.4%, respectively. These rates were stable across the whole study period (p>0.99). De novo overactive bladder was reported by 30.1% and 18.9% of patients at 3-mo and 10-yr follow-up, respectively (p for trend = 0.19). A total of 84.2% of women with detrusor overactivity received antimuscarinic drugs, but 43.8% were nonresponders 12 wk later. At multivariable analysis, maximum detrusor pressure during the filling phase >9cm H(2)O (hazard ratio [HR]: 16.2; p=0.01) and maximum detrusor pressure during the voiding phase <=29cm H(2)O (HR: 8.0; p=0.01) were independent predictors for the recurrence of SUI, as well as obesity was for the recurrence of objective SUI (HR: 17.1; p=0.01) and of USI (HR: 8.9; p=0.02), respectively. Intraoperatively, bladder perforation occurred in two cases; no severe bleeding or other complications occurred. CONCLUSIONS: The 10-yr results of this study seem to demonstrate that TVT is a highly effective option for the treatment of female SUI, recording a very high cure rate with low complications after a 10-yr follow-up. PMID- 22305111 TI - Self-report and startle-based measures of emotional reactions to body image cues as predictors of Drive for Thinness and Body Dissatisfaction in female college students. AB - The purpose was to compare self-report and psychophysiological assessment techniques in the measurement of emotional response to body image cues. Female college students (n=53; % Caucasian=53.6; M body mass index=26.1 kg/m2) completed the Eating Disorder Inventory (EDI-3) and viewed photos of themselves both unaltered and morphed to simulate weight gain. Response to the photos was assessed by self-report and the affect modulated startle paradigm. EDI-3 Drive for Thinness (DT) and Body Dissatisfaction (BD) scale scores were correlated with startled amplitude for the largest simulated weight gain photo. Startle eye blink amplitude predicted more variance in DT and BD subscales than self-reported response to the image. The affect modulated startle paradigm may provide unique information in the assessment of eating disorder symptomatology that cannot be captured via self-report techniques, and has potential to inform evaluation of treatment outcomes of eating and body image disorders. PMID- 22305112 TI - Anticoagulation for atrial fibrillation ablation: what is the optimal strategy? PMID- 22305113 TI - Feasibility and safety of dabigatran versus warfarin for periprocedural anticoagulation in patients undergoing radiofrequency ablation for atrial fibrillation: results from a multicenter prospective registry. AB - OBJECTIVES: The purpose of this study was to evaluate the feasibility and safety of periprocedural dabigatran during atrial fibrillation (AF) ablation. BACKGROUND: AF ablation requires optimal periprocedural anticoagulation for minimizing bleeding and thromboembolic complications. The safety and efficacy of dabigatran as a periprocedural anticoagulant for AF ablation are unknown. METHODS: We performed a multicenter, observational study from a prospective registry including all consecutive patients undergoing AF ablation in 8 high volume centers in the United States. All patients receiving dabigatran therapy who underwent AF ablation on periprocedural dabigatran, with the dose held on the morning of the procedure, were matched by age, sex, and type of AF with an equal number of patients undergoing AF ablation with uninterrupted warfarin therapy over the same period. RESULTS: A total of 290 patients, including 145 taking periprocedural dabigatran and an equal number of matched patients taking uninterrupted periprocedural warfarin, were included in the study. The mean age was 60 years with 79% being male and 57% having paroxysmal AF. Both groups had a similar CHADS(2) score, left atrial size, and left ventricular ejection fraction. Three thromboembolic complications (2.1%) occurred in the dabigatran group compared with none in the warfarin group (p = 0.25). The dabigatran group had a significantly higher major bleeding rate (6% vs. 1%; p = 0.019), total bleeding rate (14% vs. 6%; p = 0.031), and composite of bleeding and thromboembolic complications (16% vs. 6%; p = 0.009) compared with the warfarin group. Dabigatran use was confirmed as an independent predictor of bleeding or thromboembolic complications (odds ratio: 2.76, 95% confidence interval: 1.22 to 6.25; p = 0.01) on multivariate regression analysis. CONCLUSIONS: In patients undergoing AF ablation, periprocedural dabigatran use significantly increases the risk of bleeding or thromboembolic complications compared with uninterrupted warfarin therapy. PMID- 22305114 TI - Non-O157 Shiga toxin-producing Escherichia coli associated with venison. AB - We investigated an outbreak of non-O157 Shiga toxin-producing Escherichia coli at a high school in Minnesota, USA, in November 2010. Consuming undercooked venison and not washing hands after handling raw venison were associated with illness. E. coli O103:H2 and non-Shiga toxin-producing E. coli O145:NM were isolated from ill students and venison. PMID- 22305115 TI - Needlestick injury surveillance during mass vaccination clinics: lessons learned and why more is needed--Tri-County (Denver Metropolitan) region, Colorado, 2009. AB - Tri-County Health Department studied needlestick injury (NSI) risks in pandemic influenza A (H1N1) mass vaccination clinics through incident reports and an Internet-based vaccinator survey. The mass vaccination clinic NSI rate was 4.9 times the mean rate observed during Tri-County Health Department's 2003 to 2009 routine vaccination clinics. There was also a trend of increased risk for NSI with vaccination inexperience. These findings can be used to improve future mass vaccination clinic safety. PMID- 22305116 TI - Saccharomyces boulardii reduces infection intensity of mice with toxocariasis. AB - Several studies have shown the benefit of the use of probiotics in the prevention and treatment of diseases; however, few of them have investigated the effect of probiotics on parasitosis. In this study, the effect of Saccharomyces boulardii on the intensity of infection of mice with toxocariasis was evaluated. The animals were fed with a diet supplemented with S. boulardii for 15 days before inoculation with Toxocara canis eggs and for 2 or 60 days post-inoculation. S. boulardii promoted a reduction of approximately 36% in the average number of recovered T. canis larvae, suggesting that it can be used as an alternative to help control toxocariasis. PMID- 22305117 TI - Adipose stromal vascular fraction improves cardiac function in chronic myocardial infarction through differentiation and paracrine activity. AB - Fresh adipose-derived cells have been shown to be effective in the treatment of acute myocardial infarction (MI), but their role in the chronic setting is unknown. We sought to determine the long-term effect of the adipose derived stromal vascular fraction (SVF) cell transplantation in a rat model of chronic MI. MI was induced in 82 rats by permanent coronary artery ligation and 5 weeks later rats were allocated to receive an intramyocardial injection of 10(7) GFP expressing fresh SVF cells or culture media as control. Heart function and tissue metabolism were determined by echocardiography and (18)F-FDG-microPET, respectively, and histological studies were performed for up to 3 months after transplantation. SVF induced a statistically significant long-lasting (3 months) improvement in cardiac function and tissue metabolism that was associated with increased revascularization and positive heart remodeling, with a significantly smaller infarct size, thicker infarct wall, lower scar fibrosis, and lower cardiac hypertrophy. Importantly, injected cells engrafted and were detected in the treated hearts for at least 3 months, directly contributing to the vasculature and myofibroblasts and at negligible levels to cardiomyocytes. Furthermore, SVF release of angiogenic (VEGF and HGF) and proinflammatory (MCP-1) cytokines, as well as TIMP1 and TIMP4, was demonstrated in vitro and in vivo, strongly suggesting that they have a trophic effect. These results show the potential of SVF to contribute to the regeneration of ischemic tissue and to provide a long-term functional benefit in a rat model of chronic MI, by both direct and indirect mechanisms. PMID- 22305118 TI - Risk propensity and health risk behaviors in U.S. army soldiers with and without psychological disturbances across the deployment cycle. AB - Anecdotal and preliminary evidence suggests that Soldiers returning from a combat deployment engage in an increased number of health risk behaviors. Three potential factors driving this change were examined in this study; posttraumatic stress disorder (PTSD), concussion and traumatic brain injury (TBI), and perceived invincibility. We studied members of a combat arms brigade one month prior to a deployment to Iraq and approximately one month after their return (N = 319). Participants anonymously completed surveys characterizing attitudes about risk, risk propensity, invincibility, engagement in health risk behaviors, and personality. Using standardized screening instruments, participants were categorized with respect to PTSD and probable TBI. Results suggest that Soldiers engage in more alcohol use and reckless driving behaviors post-deployment. These changes were exaggerated in those who screened positive for PTSD. Perception of one's invincibility and survival skills increased post-deployment thus suggesting that participants felt less susceptible to adverse consequences and more adept at surviving dangerous situations. This study provides documentation of the pattern of health behavior in Soldiers engaged in the deployment cycle. Our findings suggest increases in the number of risks Soldiers' engage in post-deployment are not limited to those with PTSD symptomtotology. This study has implications for not only adjustment to life post-deployment at the individual level but also operational readiness. PMID- 22305119 TI - Effects of two stressors on amphibian larval development. AB - In parallel with a renewed interest in nuclear power and its possible environmental impacts, a new environmental radiation protection system calls for environmental indicators of radiological stress. However, because environmental stressors seldom occur alone, this study investigated the combined effects of an ecological stressor (larval density) and an anthropogenic stressor (ionizing radiation) on amphibians. Scaphiopus holbrookii tadpoles reared at different larval densities were exposed to four low irradiation dose rates (0.13, 2.4, 21, and 222 mGy d(-1)) from (137)Cs during the sensitive period prior to and throughout metamorphosis. Body size at metamorphosis and development rate served as fitness correlates related to population dynamics. Results showed that increased larval density decreased body size but did not affect development rate. Low dose rate radiation had no impact on either endpoint. PMID- 22305120 TI - Biodecontamination of water from bisphenol A using ligninolytic fungi and the modulation role of humic acids. AB - Bisphenol A (BPA) is an endocrine disruptor compound (EDC) of xenobiotic origin occurring in natural waters and wastewaters, especially in the most industrialized and urbanized areas. Recent investigations report the use of ligninolytic fungi for the removal of aromatic contaminants, including some EDCs, from different matrices. Humic acids (HA) are widely spread in all natural systems and their presence is ascertained to interfere with microbial growth and activity. The objective of this study was to assess the capacity of three ligninolytic fungi, Trametes versicolor, Stereum hirsutum and Pleurotus ostreatus, to remove BPA at the concentration of 4.6 mg L(-1) from water. Fungal growth on potato dextrose agar (PDA), in the absence and in the presence of a leonardite HA or a green compost HA, was evaluated during the biodecontamination process. The methodological approach adopted in this study excluded the presence of the mycelium in the contaminated water. Results obtained evidenced a relevant removal of BPA by any fungus when PDA only was used as growing medium. The addition of leonardite HA and compost HA stimulated the mycelial growth of any fungus, especially T. versicolor, and significantly enhanced the removal of the contaminant from water by, respectively, T. versicolor only and T. versicolor and S. hirsutum. PMID- 22305121 TI - Cartilage regeneration by culturing chondrocytes in scaffolds grafted with TATVHL peptide. AB - Formation of neocartilage is a critical issue in contemporary regenerative medicine. This study presents the generation of tissue engineering cartilage in TATVHL peptide-grafted scaffolds. Bovine knee chondrocytes were seeded in TATVHL peptide-grafted scaffolds and cultured in a spinner bioreactor. The results revealed that surface TATVHL peptide enhanced the adhesion of bovine knee chondrocytes in scaffolds. However, an increase in the concentration of TATVHL peptide in scaffolds (up to 20 MUg/mL) did not cause an evident variation in the cell viability. Surface TATVHL peptide was effective in promoting the quantity of cartilaginous components in constructs after dynamic cultivation. Biochemical assay, scanning electron microscope images, and histological staining demonstrated that surface TATVHL peptide accelerated the proliferation of bovine knee chondrocytes in constructs. In addition, the secretion of glycosaminoglycans and production of collagen in TATVHL peptide-grafted constructs were faster than those in TATVHL peptide-free constructs. TATVHL peptide can be a promising bioactive molecule to improve chondrogenesis in porous biomaterials. PMID- 22305122 TI - Protein based nanoparticles as platforms for aspirin delivery for ophthalmologic applications. AB - Most conventional ophthalmic dosage forms, though simplistic are limited by poor bioavailability in the posterior chamber of the eye. Application of nanotechnology has the potential to overcome this problem. By varying aspirin albumin ratios from 0.06 to 1.0, we obtained electrokinetically stable, pharmacologically active albumin based aspirin nanoparticles of <200 nm diameter with low polydispersity. In vitro release study showed nanoparticle formulation can release aspirin at a sustained rate for prolonged duration (90% at 72 h) and 11% drug release in the posterior chamber over a period of 72 h under simulated condition. Stability of the formulation was well maintained on storage for six months and after reconstitution for 24 h. The formulation showed no hemolysis in contrast to the high hemolysis due to the free drug. This study shows that aspirin loaded albumin nanoparticles prepared by coacervation holds promise as a formulation for topical delivery in diabetic retinopathy. PMID- 22305123 TI - Genealogical surveys show a high rate of non-paternal surname transmission with regional differences in Argentina. AB - Surnames are a vertically transmitted cultural trait that in Argentina follows the paternal line of descent when the paternity is known. There was a lack of empirical information regarding non-paternal surname transmissions among the general population, so we performed 2,550 genealogical interviews, which included 6,954 surname passes, in different regions of this country. We compared the proportion of non-paternal transmissions between the propositus and parental generation and found no significant difference between them (p<0.01). Inter population comparisons allowed us to describe 4 regional groups. We also drew models and simulations to estimate how many generations it would take to find that only half of the population maintained the paternal transmission. The lowest proportion of non-paternal transmission was 7.3%, estimating 9 generations (between 225 and 315 years) to find that, at most, half its population keeps following the paternal transmission; the highest proportion was 23%, taking 3 generations (75-105 years). Our results show a high proportion of unrecognized paternities among the general population, a very quick loss of association between male lineages and surnames, and regional proportions with significant differences between each other. PMID- 22305124 TI - Olduvai Hominin 8 foot pathology: a comparative study attempting a differential diagnosis. AB - Olduvai Hominin (OH) 8, a 1.76 million year old left foot skeleton, has osteophytic lipping on the metatarsal bases, which when compared to a modern sample, may help paleoanthropologists determine whether the foot bones represent an injured subadult or an osteoarthritic adult. This study compares the OH 8 lipping pattern to those of 140 individual Amerindians comprising four different age classes to determine whether the OH 8 lipping is likely to be age-related osteoarthritis. OH 8 metatarsal lipping followed a pattern similar to that determined in the comparative sample to be age-related osteoarthritis. Similarities include metatarsal base lipping that is frequently located on the dorsal surface, metatarsal base lipping that is more severe on the lateral metatarsals compared to the medial metatarsals, and the presence of a pseudojoint between metatarsal 1 and metatarsal 2. The chance of finding an individual with osteoarthritis lipping increases from 3.45% in the age group 18-22 years to 55% in individuals over 35 years. The chance of finding a pseudojoint increases from 1.32% in non-osteoarthritic individuals to 15.15% in individuals with osteoarthritis. Results from this study indicate that the OH 8 foot bones are most likely from an adult and more likely to belong to Paranthropus boisei, the skull of which was found in the same excavations with OH 8, than to the juvenile Homo habilis holotype. PMID- 22305125 TI - Phenylketonuria: nutritional advances and challenges. AB - Despite the appearance of new treatment, dietary approach remains the mainstay of PKU therapy. The nutritional management has become complex to optimize PKU patients' growth, development and diet compliance. This paper review critically new advances and challenges that have recently focused attention on potential relevant of LCPUFA supplementation, progress in protein substitutes and new protein sources, large neutral amino acids and sapropterin. Given the functional effects, DHA is conditionally essential substrates that should be supplied with PKU diet in infancy but even beyond. An European Commission Programme is going on to establish quantitative DHA requirements in this population. Improvements in the palatability, presentation, convenience and nutritional composition of protein substitutes have helped to improve long-term compliance with PKU diet, although it can be expected for further improvement in this area. Glycomacropeptide, a new protein source, may help to support dietary compliance of PKU subject but further studies are needed to evaluate this metabolic and nutritional issues. The PKU diet is difficult to maintain in adolescence and adult life. Treatment with large neutral amino acids or sapropterin in selected cases can be helpful. However, more studies are necessary to investigate the potential role, dose, and composition of large neutral amino acids in PKU treatment and to show long-term efficacy and tolerance. Ideally treatment with sapropterin would lead to acceptable blood Phe control without dietary treatment but this is uncommon and sapropterin will usually be given in combination with dietary treatment, but clinical protocol evaluating adjustment of PKU diet and sapropterin dosage are needed.In conclusion PKU diet and the new existing treatments, that need to be optimized, may be a complete and combined strategy possibly positive impacting on the psychological, social, and neurocognitive life of PKU patients. PMID- 22305126 TI - Voluntary post weaning exercise restores metabolic homeostasis in offspring of obese rats. AB - AIM: Physical exercise reduces obesity, insulin resistance and dyslipidemia. We previously found that maternal obesity alters central appetite circuits and contributes to increased adiposity, glucose intolerance and metabolic disease in offspring. Here we hypothesized that voluntary exercise would ameliorate the adverse metabolic effects of maternal obesity on offspring. METHODS AND RESULTS: Sprague-Dawley females fed chow (C) or high-fat diet HFD (H) were mated. Female offspring from C dams were weaned onto chow (CC); those from H dams recieved chow (HC) or HFD (HH). Half of each group was provided with running wheels (CC(EX), HC(EX), HH(EX); n=10-12). Maternal obesity increased body weight (12%), adiposity, plasma lipids and induced glucose intolerance (HC vs CC; P<0.05). These were exaggerated by postweaning HFD (HH vs HC; P<0.01), showed doubled energy intake, a 37% increase in body weight, insulin resistance and glucose intolerance (HH vs HC; P<0.01). Exercise reduced fat mass, plasma lipids, HOMA and fasting glucose in HC(EX) (vs HC; P<0.05) and HH(EX) (vs HH; P<0.01). Values in HC(EX) were indistinguishable from CC, however in HH(EX) these metabolic parameters remained higher than the sedentary HC and CC rats (P<0.01). mRNA expression of hypothalamic pro-opiomelanocortin, and adipose tumour necrosis factor alpha and 11beta-hydroxysteroid dehydrogenase type 1 were reduced by exercise in HH(EX) (vs HH; P<0.05). CONCLUSION: While voluntary exercise almost completely reversed the metabolic effects of maternal obesity in chow fed offspring, it did not fully attenuate the increased adiposity, glucose intolerance and insulin resistance in offspring weaned onto HFD. PMID- 22305127 TI - Dengue surveillance among French military in Africa. PMID- 22305128 TI - Strength and aerobic requirements during stair ambulation in persons with chronic stroke and healthy adults. AB - OBJECTIVE: To estimate the cost of stair ascent and descent in relation to a measured standard of strength and metabolic (aerobic) capacities in persons with chronic stroke compared with healthy adults. DESIGN: Descriptive cross-sectional study. SETTING: Motion analysis laboratory. PARTICIPANTS: Persons with stroke (n=10) and sex- and age-matched older adults (n=10). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Lower limb peak joint moments generated during stair walking, expressed as a percentage of the respective isokinetic peak torque, provided an estimate of the relative strength cost. The oxygen consumed during stair walking as a percentage of the maximum oxygen consumption estimated from a submaximal cycle ergometer test reflected the relative aerobic cost of stair ambulation. RESULTS: During ascent, plantarflexor strength cost was highest on the affected side (stroke) compared with the less affected side and control subjects. The costs associated with the knee extensors were highest in stroke (both sides) for both ascent and descent, and similarly the costs were highest for the less affected and affected plantarflexors during descent. No differences were detected between the affected and less affected sides. The oxygen consumed when ambulating 1 flight of stairs was comparable between groups, but the relative aerobic cost of stair ascent and descent was higher in stroke survivors because of their lower aerobic capacity. CONCLUSIONS: To our knowledge, this is the first study to compare the relative costs of stair ambulation in people with stroke and healthy controls. The higher strength and aerobic costs associated with stair negotiation in stroke resulting primarily from reduced strength and aerobic capacities, respectively, may limit mobility. PMID- 22305129 TI - Geographic access to and availability of community resources for persons diagnosed with severe mental illness in Philadelphia, USA. AB - This study assesses whether there are differences in geographic access to and availability of a range of different amenities for a large group of persons diagnosed with severe mental illness (SMI) in Philadelphia (USA) when compared to a more general set of residential addresses. The 15,246 persons who comprised the study group had better outcomes than an equal number of geographical points representative of the general Philadelphia population on measures of geographic proximity and availability for resources considered important by people diagnosed with SMI. These findings provide support for the presence of geographic prerequisites for attaining meaningful levels of community integration. PMID- 22305130 TI - The Rice stripe virus pc4 functions in movement and foliar necrosis expression in Nicotiana benthamiana. AB - The Rice stripe virus (RSV) pc4 has been determined as the viral movement protein (MP). In this study, the pc4 gene was cloned into a movement-deficient Tobacco mosaic virus (TMV). The resulting hybrid TMV-pc4, in addition to spreading cell to cell in Nicotiana tabacum, moved systemically and induced foliar necrosis in Nicotiana benthamiana, indicating novel functions of the RSV MP. A systematic alanine-scanning mutagenesis study established the region K(122)-D(258) of the pc4 substantially associated with cell-to-cell movement, and mutants by replacement of KGR(122-124), D(135), ED(170-171), ER(201-202), EFE(218-220) or ELD(256-258) with alanine(s) no longer moved cell to cell. However, only one amino acid group KGR(122-124) was linked with long-distance movement. The region D(17)-K(33) was recognized as a crucial domain for leaf necrosis response, and mutagenesis of DD(17-18) or RK(32-33) greatly attenuated necrosis. The overall data suggested manifold roles of the pc4 during the RSV infection in its experimental host N. benthamiana. PMID- 22305132 TI - [Possibility to screen COPD in emergency department]. AB - INTRODUCTION: The COPD is a stake of public health because of its prevalence in the world, its morbi-mortality and its considerable cost (2,2 billion euros/year in France). An early screening allows for a fast and effective intervention. MATERIAL AND METHOD: The prospective study with in the emergency department of Roanne included smokers and ex-smokers, more than 10PY for the 40 years old and older, more than 20PY for the others, and/or symptomatic of COPD. Screening rested on a questionnaire filled out by the patient. Are excluded patients already diagnosed with COPD. This screening is carried out with the FEV1/FEV6. The criterion of principal judgment rests on the time taken for screening and acceptability by the patients. RESULTS: One hundred and twenty-two patients were included, 6.5% refused screening. The average time of screening was 4.8 minutes. There were 27 positive patients with the FEV1/FEV6, 14 came to make the classic spirometry. Only 10.53% have a FEV1/FEV6<0.73. On the whole, 15.86% do not have a COPD, 75,25% are at the risk of COPD, 5,94% have a COPD stage 1, 1,98% are stage 2, 0.99% stage 3 and none stage 4. DISCUSSION: The study thus showed that a screening of the COPD in the emergency rooms is possible because of the simple and reproductible process. Its shows, however its limits since the number of inclusion decrease during days of strong attendance in emergency rooms. CONCLUSION: The screening of the COPD as foreseen in the study is possible. PMID- 22305131 TI - Interferon-alpha/beta deficiency greatly exacerbates arthritogenic disease in mice infected with wild-type chikungunya virus but not with the cell culture adapted live-attenuated 181/25 vaccine candidate. AB - In humans, chikungunya virus (CHIKV) infection causes fever, rash, and acute and persisting polyarthralgia/arthritis associated with joint swelling. We report a new CHIKV disease model in adult mice that distinguishes the wild-type CHIKV-LR strain from the live-attenuated vaccine strain (CHIKV-181/25). Although eight week old normal mice inoculated in the hind footpad developed no hind limb swelling with either virus, CHIKV-LR replicated in musculoskeletal tissues and caused detectable inflammation. In mice deficient in STAT1-dependent interferon (IFN) responses, CHIKV-LR caused significant swelling of the inoculated and contralateral limbs and dramatic inflammatory lesions, while CHIKV-181/25 vaccine and another arthritogenic alphavirus, Sindbis, failed to induce swelling. IFN responses suppressed CHIKV-LR and CHIKV-181/25 replication equally in dendritic cells in vitro whereas macrophages were refractory to infection independently of STAT1-mediated IFN responses. Glycosaminoglycan (GAG) binding may be a CHIKV vaccine attenuation mechanism as CHIKV-LR infectivity was not dependent upon GAG, while CHIKV-181/25 was highly dependent. PMID- 22305133 TI - [Miliary tuberculosis in Mali during the decade 2000-2009]. AB - In order to describe the epidemio-clinical and evolutionary aspects of miliary tuberculosis (TB) in Mali, a retrospective study of 10 years (1 January 2000 to December 31, 2009) was conducted in the service of pneumo-phtisiology at the university hospital of point G. It concerned all patients with radiological images compatible with miliary TB, signs of bacillary impregnation, bacillus or not, treated with antituberculosis drugs. Of 3630 TB patients all forms recorded during the study period, 183 miliary were recorded (5%) including 117 men and 66 women. Young adults between 29-45 years were more represented (52%). The average diagnostic delay was 3.7 months. The symptomatology was dominated by the fever (100%), cough (90.1%) and asthenia (86.3%), anorexia (81.9%). The radiological images types of micronodular opacities were the most frequent in 147 cases (80.3%) against 36 cases of (19.7%) macronodular types. Bacteriological examination of sputum was negative in 139 patients (76%) and positive in 44 patients (24%). There was a statistically significant relationship between the presence of an excavation in Chest radiography and smear positivity (P<0.001). The clinical improvement observed (55.7%) depended on the time of the diagnosis (P<0.001). The serology HIV was positive at 29 patients on 124 tested. Also, in areas with high prevalence TB/HIV, any miliary fever in the absence of other obvious etiologies should undertake without delay TB proper treatment. PMID- 22305134 TI - [Desmoplastic mesothelioma with bony metastases. A case report]. AB - Desmoplastic mesothelioma is unusual variant of malignant mesothelioma. The diagnosis of desmoplastic mesothelioma represents one of the most difficult exercises in pleural pathology (with poor interobservers agreement) because of their abundant collagen with relatively low cellularity. The clinical course is often rapid with visceral metastases. Bony metastases have only rarely been noted. We report our case of desmoplastic mesothelioma with vertebral metastases. Our focus is to distinguish this entity from fibrous pleurisy and localized fibrous tumors, to explain histological and immunohistochemical features with review of the literature. PMID- 22305135 TI - [Huge aspergilloma developed within a zone of scleroderma-related pulmonary fibrosis]. AB - In pulmonary aspergilloma, Aspergillus colonizes and proliferates as a saprophyte in deterged cavities deprived of local defense. Although pulmonary tuberculosis constitutes the one well-know predisposing factor, other causes can create favorable conditions. We describe a first published case of a huge aspergilloma which developed within a zone of pulmonary fibrosis secondary to systemic scleroderma. The patient was a 58-year-old woman in poor general health who experienced repeated episodes of hemoptysis and dyspnea. Physical examination disclosed sclerodactyly, generalized cutaneous sclerosis and Raynaud's phenomenon. There was no clinical history of pulmonary tuberculosis or bronchectasis. Aspergillosis serology was positive. Broncho-alveolar liquid was positive for Aspergillus fumigatus at direct examination and after culture. Immunological assessment confirmed scleroderma. The chest computed tomography scan showed a huge oblong-shaped opacity in the upper left lobe which had developed within a zone of pulmonary fibrosis. Medical management was instituted. The clinical course was marked by repeating hemoptysis and the stability of pulmonary lesions after two years. Management of scleroderma-related pulmonary aspergiloma remains difficult and complicated. Prognosis depends on the course of both conditions, scleroderma and aspergillosis. PMID- 22305136 TI - [Disseminated pulmonary actinomycosis with hepatic injury: a misleading form mimicking a polymetastatic picture]. AB - INTRODUCTION: Thoracic actinomycosis, caused by bacteria of the Actinomyces genus, is a rare infection, with poor prognosis if untreated, whose clinical and radiological picture is misleading, which can simulate a tumoral or tuberculous disease. CLINICAL CASE: This is a case of generalised pseudotumoral pulmonary actinomycosis in a non-smoking, non-drinking 48-year-old man, who for one month has been presenting a cough with haemoptoic sputum, dyspnoea associated with fever and a deterioration in general condition. The clinical examination discovered weight loss, diffuse crackling rales and multiple dental caries. Biologically, he presented an inflammatory syndrome. The radiological imaging and lung and liver CT-scans discovered a peripheral lung mass right side associated with multiple nodular cannon-ball opacities, multiple liver lesions of metastatic appearance. The bacteriological examination of the bronchoalveolar lavage fluid (Gram stain and culture) and the transparietal biopsy of the lung mass confirmed the presence of Actinomyces. Progress under treatment with 10 million international units of parenteral penicillin G daily over a period of six weeks substituted by three grams of amoxicillin/clavulanic acid daily over a period of 12 months and following an oral preparatory procedure was favourable. The thoraco abdominal scan carried out three months after the treatment showed that the lesions had completely disappeared. CONCLUSION: Our case illustrates the diagnostic difficulty of actinomycosis particularly faced with a picture of multiple lung and liver metastasis. Hence, the importance of a histological and bacteriological examination of samples. The prognosis of this complaint is generally good following well-managed, prolonged treatment; and the prognosis peculiar to disseminated forms is less certain. PMID- 22305137 TI - [Blastomycosis in Morocco: imported mycosis]. AB - Blastomycosis is a rare case. We report a first Moroccan case. A 41-year-old male presented with a 6-month history of dyspnea, fever and significant chest pain associated with night sweats and weight loss. The physical examination disclosed a firm painful paravertebral mass. The chest radiograph demonstrated a left apical opacity. The thoracic scan showed parenchymal infiltration of the apico dorsal segment of the left upper lobe with vertebral and costal lytic lesions. Surgical biopsy showed granulomatous inflammation with giant-cell intracytoplasmic inclusions. Fungal studies yielded Blastomyces dermatitidis which responded excellently to ketoconazole. Outcome has been excellent at 3.5 years months follow-up. The clinical and radiographic presentation of blastomycosis is non-specific and can be mistaken for a neoplasm. Delay in diagnosis is common. PMID- 22305138 TI - [Simvastatin indused chylothorax]. AB - Chylothorax is a rare disorder occurring most often in aftermath of a thoracic surgery or during cancer of mediastinum. We report the clinical history of the world's second case of chylothorax which appeared during treatment with simvastatin. PMID- 22305139 TI - [Intrathoracic lymphadenopathy: an unusual manifestation of rheumatoid arthritis]. AB - Lung disease is the most frequent extra-articular manifestation of rheumatoid arthritis. It is detected in nearly 50% of patients with this multisystem affection, his knowledge has benefited from advances in computed tomography (CT). The inflammation can affect the pleura, the airways and the lung parenchyma. Intrathoracic lymphadenopathy complicating rheumatoid lung are not usual, and then pose the problem of differential diagnosis. We report a 51-year-old man, with a history of tobacco intoxication, suffering from rheumatoid arthritis who developed an interstitial lung disease at stage of fibrosis with mediastinal and hilar adenopathy. We will discuss the clinical, paraclinical, evolutionary and therapeutic particularities case. PMID- 22305140 TI - [Hepatopulmonary syndrome: a complication of type 1 Gaucher disease]. AB - Gaucher's disease is a not exceptional lysosomial disease in Tunisia. Type 1 is by far the most common one. Pulmonary involvement is considered to be rare in type 1 Gaucher's disease. Pulmonary hypertension, infiltration of the lungs with Gaucher cells, and severe hypoxemia due to intrapulmonary arterial-venous shunts, have been described in case reports and small case series. We reported the case of hepatopulmonary syndrome in a 14-year-old boy with type 1 Gaucher disease. The diagnosis of Gaucher disease was established, at 2 years age, by enzyme assay of leucocyte beta-glucosidase. The patient presented dyspnoea, digital clubbing and cyanosis of the lips. The arterial blood gas found severe hypoxaemia with PaO(2) at 56.9 mmHg. The diagnosis of hepatopulmonary syndrome, in our patient, was confirmed by demonstration of the intrapulmonary shunting using contrast-enhanced echocardiography and the technetium-99m-labeled macroaggregated albumin. The patient was treated by symptomatic measure, long term oxygen therapy because the insufficiency of the enzyme replacement therapy. Screening for hypoxemia in children with liver disease should be considered. PMID- 22305141 TI - Mechanism of glutamate receptor for excitation of medial vestibular nucleus induced by acute hypotension. AB - In the vestibular nuclei, acute hypotension induces excitation of electrical activity and expression of c-Fos protein and phosphorylated extracellular signal regulated kinase (pERK). Expression of c-Fos protein and pERK is mediated by the excitatory neurotransmitter, glutamate. We investigated the signaling pathway of glutamate and its receptors in the vestibular nuclei following acute hypotension in conscious rats. Glutamate release and the expression of c-Fos protein in the medial vestibular nuclei (MVN) were measured by microdialysis and immunohistochemical analysis, respectively. We compared the responses of rats with unilateral labyrinthectomy to unaltered controls. Acute hypotension was induced by infusing sodium nitroprusside (SNP) into the femoral vein. In the control group, glutamate release and the expression of c-Fos protein increased in the bilateral MVN following acute hypotension. In the unilateral labyrinthectomy group, glutamate release and the expression of c-Fos protein increased in the MVN contralateral to the lesion, but did not change in the ipsilateral MVN following acute hypotension. Microinjection of NMDA or AMPA into the lateral ventricle increased the expression of c-Fos protein in the bilateral MVN of conscious intact labyrinthine rats. However, after intracerebroventricular microinjection of MK-801 or CNQX little c-Fos protein was expressed in the bilateral MVN of these rats following acute hypotension. These results suggest that in response to acute hypotension, excitatory afferent signals from the peripheral vestibular receptors release glutamate into postsynaptic neurons in the vestibular nuclei. These excitatory signals are transmitted through the NMDA receptors and AMPA receptors of glutamate in the vestibular system. PMID- 22305142 TI - Conflict adjustment through domain-specific multiple cognitive control mechanisms. AB - Cognitive control is required to regulate conflict between relevant and irrelevant information. Although previous neuroimaging studies have focused on response conflict, recent studies suggested that distinct neural networks are recruited in regulating perceptual conflict. The aim of the current study was to distinguish between brain areas involved in detecting and regulating perceptual conflict using a conflict adjustment paradigm. The Stroop color-matching task was combined with an arrow version of the Stroop task in order to independently manipulate perceptual and response conflicts. Behavioral results showed that post conflict adjustment for perceptual and response conflicts were independent from each other. Imaging results demonstrated that the caudal portion of the dorsal cingulate cortex (cdACC) was selectively associated with the occurrence of perceptual conflict, whereas the left dorsal portion of the premotor cortex (pre PMd) was selectively associated with both preceding and current perceptual conflict trials. Furthermore, the rostral portion of the dorsal cingulate cortex (rdACC) was selectively linked with response conflict, whereas the left dorsolateral prefrontal cortex (DLPFC) was selectively involved in both preceding and current response conflict trials. We suggest that cdACC is involved in detecting perceptual conflict and left pre-PMd is involved in regulating perceptual conflict, which is analogous to the recruitment of rdACC and left DLPFC in control processes for response conflict. Our findings provide support for the hypothesis that multiple independent monitor-controller loops are implemented in the frontal cognitive control system. PMID- 22305143 TI - Within-limb somatotopic organization in human SI and parietal operculum for the leg: an fMRI study. AB - Somatotopic organizations in human somatosensory cortex (SI and SII) for scattered portions of the leg have not been systematically observed with functional magnetic resonance imaging (fMRI). In this research we compared functional representations in the contralateral SI and bilateral parietal operculum (that contained subregions OP1, 3-4 of SII and OP2) of four acupoints in right leg in proximal-distal and medial-lateral arrangement. The results were: (1) somatotopy of SI demonstrated a lateral-to-medial and inferior-to-superior pattern when acupoints were shifting from proximal to distal or from medial to lateral; (2) the contralateral OP1 also showed a clear somatotopic organization for the four separated leg portions, and the ipsilateral OP1 showed a similar pattern to the contralateral OP1, thus arrangements of responses in the two areas were mirror-symmetric against y-axis; (3) the contralateral OP2 showed a somatotopic organization when acupoints shifting from proximal to distal, while the contralateral OP3 presented a trend of somatotopy opposite to that of the contralateral OP1. These results first show definite within-leg somatotopy of human SI for scattered leg portions in medial-lateral arrangement using fMRI. Within-limb somatotopic organization of OP1 for leg portions arranging from proximal to distal as well as from medial to lateral, and somatotopy of OP2 for leg portions arranging from proximal to distal, are also shown for the first time. Our results also reinforce the proposal of a somatotopic map existing in human OP3, and indicating a fourth somatotopic map in OP2 in human parietal operculum, which suggests that OP 2 is not just a vestibular area. In addition, separable activations in somatosensory cortex induced by adjacent acupoints should play a fundamental role in acupoint-specific effects in the brain. PMID- 22305144 TI - Estradiol protects against hippocampal damage and impairments in fear conditioning resulting from transient global ischemia in mice. AB - Estradiol protects against hippocampal damage and some learning impairments resulting from transient global ischemia in rats. Here, we seek to validate a mouse model of transient global ischemia and evaluate the effects of estradiol on ischemia-induced hippocampal damage and behavioral impairments. Female C57Bl6/J mice were ovariectomized and implanted with estradiol- or oil-secreting capsules. One week later, mice experienced 15-min of 2-vessel occlusion (2-VO) or sham surgical procedures. Five days later, mice were exposed to a fear conditioning protocol in which a specific context and novel tone were paired with mild footshock. Twenty-four hours following conditioning, contextual fear was assessed by measuring freezing behavior in the conditioned context (in the absence of the tone). This was followed by assessment of cue fear by measuring freezing behavior to the conditioned tone presented in a new context. When tested in the conditioned context, oil-treated mice that experienced 2-VO exhibited a significant reduction in freezing behavior whereas estradiol-treated mice that experienced 2-VO showed no disruption in freezing behavior. Freezing behavior when presented with the conditioned tone was unaffected by either surgery or hormone treatment. These findings suggest that global ischemia causes impairments in performance on the hippocampally-dependent contextual fear task but not conditioned cue-based fear. Furthermore, estradiol prevented the ischemia-induced impairment in contextual fear conditioning. Fluoro-Jade (FJ) staining revealed neuronal degeneration throughout the dorsal hippocampus of mice that experienced 2-VO. Estradiol treatment reduced the number of FJ+ cells in CA1 and CA2, but not in CA3 or in the dentate gyrus. Together, these findings suggest that 15 min of global ischemia causes extensive hippocampal neurodegeneration and disrupts contextual fear conditioning processes in mice and that estradiol protects against these adverse effects. PMID- 22305145 TI - General, kappa, delta and mu opioid receptor antagonists mediate feeding elicited by the GABA-B agonist baclofen in the ventral tegmental area and nucleus accumbens shell in rats: reciprocal and regional interactions. AB - Food intake is significantly increased following administration of agonists of GABA and opioid receptors into the nucleus accumbens shell (NACs) and ventral tegmental area (VTA). GABA-A or GABA-B receptor antagonist pretreatment within the VTA or NACs differentially affects mu-opioid agonist-induced feeding elicited from the same site. Correspondingly, general or selective opioid receptor antagonist pretreatment within the VTA or NACs differentially affects GABA agonist-induced feeding elicited from the same site. Regional interactions have been evaluated in feeding studies by administering antagonists in one site prior to agonist administration in a second site. Thus, opioid antagonist-opioid agonist and GABA antagonist-GABA agonist feeding interactions have been identified between the VTA and NACs. However, pretreatment with GABA-A or GABA-B receptor antagonists in the VTA failed to affect mu opioid agonist-induced feeding elicited from the NACs, and correspondingly, these antagonists administered in the NACs failed to affect mu opioid-induced feeding elicited from the VTA. To evaluate whether regional and reciprocal VTA and NACs feeding interactions occur for opioid receptor modulation of GABA agonist-mediated feeding, the present study examined whether feeding elicited by the GABA-B agonist, baclofen microinjected into the NACs was dose-dependently blocked by pretreatment with general (naltrexone: NTX), mu (beta-funaltrexamine: BFNA), kappa (nor-binaltorphamine: NBNI) or delta (naltrindole: NTI) opioid antagonists in the VTA, and correspondingly, whether VTA baclofen-induced feeding was dose dependently blocked by NACs pretreatment with NTX, BFNA, NBNI or NTI in rats. Bilateral pairs of cannulae aimed at the VTA and NACs were stereotaxically implanted in rats, and their food intakes were assessed following vehicle and baclofen (200 ng) in each site. Baclofen produced similar magnitudes of increased food intake following VTA and NACs treatment. Baclofen administration in the VTA or NACs was also preceded by administration of NTX (0.1, 1, 5 MUg, 0.5 h), BFNA (0.4, 4 MUg, 24 h), NBNI (0.6, 6 MUg, 0.5 h) or NTI (0.4, 4 MUg, 0.5 h) into the other site with intake measured 1, 2 and 4 h after agonist treatment. VTA NTX significantly reduced NACs baclofen-induced feeding. Correspondingly, NACs NTX significantly reduced VTA baclofen-induced feeding, indicating a robust and bidirectional general opioid and GABA-B receptor feeding interaction. Whereas the high, but not low VTA BFNA dose reduced NACs baclofen-induced feeding, NACs BFNA failed to affect VTA baclofen-induced feeding, indicating a unidirectional mu opioid and GABA-B receptor feeding interaction. Whereas VTA NBNI at both doses reduced NACs baclofen-induced feeding, the high, but not low NACs NBNI dose significantly reduced VTA baclofen-induced feeding, indicating a bidirectional kappa opioid and GABA-B receptor feeding interaction. Whereas VTA NTI only transiently reduced NACs baclofen-induced feeding, NACs NTI failed to affect VTA baclofen-induced feeding, indicating a weak unidirectional delta opioid and GABA B receptor interaction. Whereas administration of NTX or BFNA into the NACs or VTA marginally reduced spontaneous food intake, NBNI or NTI into the same sites failed to alter food intake alone. Therefore, the present study suggests that GABA employs a distributed brain network in mediating its ingestive effects that is dependent upon intact opioid receptor signaling with kappa opioid receptors more involved than mu and delta opioid receptors underlying these regional effects. An alternative hypothesis to be considered is that these effects could be the sum of two independent drug effects (opioid antagonists decreasing and baclofen increasing food intake). PMID- 22305147 TI - Acute aortic regurgitation with myocardial infarction: an important clue for aortic dissection. AB - BACKGROUND: Aortic dissection is an important cause of acute chest pain that should be rapidly diagnosed, as mortality increases with each hour this condition is left untreated. The diagnosis can be challenging, especially if concomitant myocardial infarction is present. Echocardiography is an important tool for the differential diagnosis. OBJECTIVES: To stress the importance of recognizing aortic regurgitation for the differentiation of myocardial infarction and aortic dissection. CASE REPORT: An 80-year-old woman was admitted to our hospital with chest pain that was diagnosed as inferior and lateral wall myocardial infarction based on electrocardiographic findings. The diagnosis was reevaluated when aortic regurgitation was detected on echocardiography. Closer inspection of the ascending aorta revealed a dissection flap as the cause of aortic regurgitation. CONCLUSION: Detection of aortic regurgitation in a patient with myocardial infarction and normal valves should prompt the search for a possible aortic dissection, whether or not the dissection flap can be visualized. PMID- 22305146 TI - Supplemental dietary choline during development exerts antidepressant-like effects in adult female rats. AB - Perinatal choline supplementation in rats is neuroprotective against insults such as fetal alcohol exposure, seizures, and advanced age. In the present study we explored whether dietary choline supplementation may also confer protection from psychological challenges, like stress, and act as a natural buffer against stress linked psychological disorders, like depression. We previously found that choline supplementation increased adult hippocampal neurogenesis, a function compromised by stress, lowered in depression, and boosted by antidepressants; and increased levels of growth factors linked to depression, like brain-derived neurotrophic factor. Together, these were compelling reasons to study the role of choline in depressed mood. To do this, we treated rats with a choline supplemented diet (5 mg/kg choline chloride in AIN76A) prenatally on embryonic days 10-22, on postnatal days (PD) 25-50, or as adults from PD75 onward. Outside of these treatment periods rats were fed a standard diet (1.1 mg/kg choline chloride in AIN76A); control rats consumed only this diet throughout the study. Starting on PD100 rats' anxiety-like responses to an open field, learning in a water maze, and reactivity to forced swimming were assessed. Rats given choline supplementation during pre- or post-natal development, but not adult-treated rats, were less anxious in the open field and less immobile in the forced swim test than control rats. These effects were not mediated by a learning deficit as all groups performed comparably and well in the water maze. Thus, we offer compelling support for the hypothesis that supplemental dietary choline, at least when given during development, may inoculate an individual against stress and major psychological disorders, like depression. PMID- 22305148 TI - Latency of pulse oximetry signal with use of digital probes associated with inappropriate extubation during prehospital rapid sequence intubation in head injury patients: case examples. AB - BACKGROUND: Endotracheal intubation remains the definitive skill needed for airway management of both medical and surgical patients treated in the prehospital and hospital arenas. Subsequently, rapid sequence intubation (RSI) protocols have been established for various first-line emergency service providers. Because RSI results in the paralysis of skeletal muscles, with a subsequent period of apnea and an increased potential for oxygen desaturation, the accuracy of pulse oximetry (SpO(2)) data is critical in guiding pre oxygenation efforts and indicating abandonment of intubation attempts to avoid hypoxic injury. Latency of up to 120 s has been demonstrated in conditions producing peripheral vasoconstriction. The influence of peripheral oximetry on the decision-making process during the establishment of a definitive airway has not, to our knowledge, been previously investigated in the prehospital setting. OBJECTIVE: To demonstrate how signal latency may manifest itself as a perceived oxygen desaturation with a subsequent premature abortion of a primary RSI attempt or erroneous extubation. CASE EXAMPLES: We document endotracheal extubation associated with pulse oximetry signal latency during prehospital RSI with the use of digital SpO(2) probes. Two case examples are presented that are taken from a retrospective analysis of pre-hospital RSI data recorded by the City of San Diego Emergency Medical Services. CONCLUSION: To avoid the possibility of mistaking oximetry signal latency for oxygen desaturation during pre-hospital RSI, we propose a conservative approach of aggressive pre-oxygenation to SpO(2) values>=94%, and the use of quantitative continuous capnometry for decision making regarding whether the endotracheal tube is correctly placed. In cases of hypoxemia despite a properly placed tube, focus should be turned to other causes of post intubation hypoxemia. PMID- 22305150 TI - Cardiac rupture. AB - BACKGROUND: Cardiac rupture is an unusual cause of chest pain and sudden cardiovascular collapse. This diagnosis may be easily forgotten while managing a patient in extremis in the initial minutes of evaluation and resuscitation in the emergency department (ED). OBJECTIVES: To report the benefit of immediate bedside cardiac ultrasonography in the diagnosis of cardiac rupture and its influence on emergent intervention in the ED. CASE REPORT: The initial electrocardiogram, performed within 5 min of arrival, of a 65-year old man who presented with 20 min duration of chest pain, showed a biphasic T wave in V1 and inverted T wave in V2, without ST-segment elevation myocardial infarction. Fifteen minutes later, he lost consciousness and was pulseless without a shockable rhythm on the monitor. Chest compressions were started and the patient was intubated. Echocardiography was performed at the bedside by the emergency physician. Cardiac contractility was grossly decreased in both ventricles and a large amount of pericardial fluid was seen. Two attempts at ultrasound-guided pericardiocentesis yielded only a few milliliters of blood. Interruptions in chest compressions were minimized during pericardiocentesis. Before transport of the patient to the operating room for definitive repair, asystole occurred. On the subsequent echocardiogram, heart contractions were absent and a hematoma was seen in the pericardial space. Resuscitation efforts were stopped. An autopsy was not performed per family request. CONCLUSIONS: Typical ultrasonographic findings of cardiac rupture were present in this patient, who presented in extremis with chest pain. Early bedside echocardiography can be helpful in directing the initial care of critically ill patients. PMID- 22305149 TI - Comparative sensitivity of computed tomography vs. magnetic resonance imaging for detecting acute posterior fossa infarct. AB - BACKGROUND: Posterior fossa strokes, particularly those related to basilar occlusion, pose a high risk for progression and poor neurological outcomes. The clinical history and examination are often not adequately sensitive or specific for detection. STUDY OBJECTIVES: Because this population stands to benefit from acute interventions such as intravenous and intra-arterial tissue plasminogen activator, mechanical thrombectomy, and intensive monitoring for neurologic deterioration, this study examined the sensitivity of non-contrast head computed tomography (NCCT) for diagnosing posterior fossa strokes in the emergency department. METHODS: This study analyzed a prospectively collected database of acute ischemic stroke patients who underwent head NCCT within 30 h of symptom onset and who were subsequently found to have a posterior fossa infarct on brain magnetic resonance imaging (MRI) performed within 6 h of the NCCT. RESULTS: There were 67 patients identified who had restricted diffusion on MRI in the posterior fossa. The National Institutes of Health Stroke Scale (NIHSS) scores ranged from 0 to 36, median 3. Only 28 patients had evidence of infarction on the initial NCCT scan. The timing of NCCT scans ranged from 1.2 to 28.9 h after symptom onset. The sensitivity of NCCT was 41.8% (95% confidence interval 30.1-54.4). The longest period of time between symptom onset and a negative NCCT with a subsequent positive diffusion-weighted imaging MRI was 26.7 h. CONCLUSIONS: Head NCCT imaging is frequently insensitive for detecting posterior fossa infarction. Temporal evolution of strokes in this distribution, coupled with beam-hardening artifact, may contribute to this limitation. When a posterior fossa stroke is suspected and the NCCT is non-diagnostic, MRI is the preferred imaging modality to exclude posterior fossa infarction. PMID- 22305151 TI - A physician's got to know his (test's) limitations. PMID- 22305152 TI - Recurrent spontaneous globe subluxation: a case report and review of manual reduction techniques. AB - BACKGROUND: Spontaneous globe subluxation is an uncommon problem that develops acutely and can present with significant patient distress from ocular pain and vision loss. OBJECTIVES: To present an unusual case of recurrent spontaneous globe subluxation and describe several methods emergency physicians can use to reduce a subluxation. CASE REPORT: We describe a patient with recurrent spontaneous globe subluxation who presented to the Emergency Department with acute ocular pain and vision loss. The subluxation was emergently reduced, resolving the pain and restoring normal vision. Various manual reduction techniques are discussed. CONCLUSION: There are a number of manual reduction techniques used for treating spontaneous globe subluxation. PMID- 22305153 TI - In vitro and in vivo safety evaluation of Dipteryx alata Vogel extract. AB - BACKGROUND: Dipteryx alata Vogel popularly known as "baru" is an important commercial leguminous tree species from the Brazilian Cerrado, which possess medicinal properties, besides its fruits consumption by animals and humans. The use of the "naturally occurring plants" as herbal remedies and foods mainly from leaves, seeds, flowers and roots of plants or extracts require precautions before ensuring these are safe and efficacious. The objective of this study was to evaluate the safety of D. alata barks extract. METHODS: Vegetal drugs of D. alata barks were submitted to quality control assays and further to the safety assays under 1) in vitro parameter by Salmonella (Ames) mutagenicity, and 2) in vivo parameter on the pregnancy of rats. RESULTS: The extract was non-mutagenic to any of the assessed strains TA97a, TA98, TA100 and TA102 even after metabolic activation (+S9). All in vivo parameters (reproductive ability evaluation, physical development of rat offsprings, and neurobehavioral development assays) showed no changes related to control group. CONCLUSION: D. alata barks extract is neither mutagenic by the Ames test nor toxic in the pregnancy of rats, with no physical-neurobehavioral consequences on the rat offsprings development. PMID- 22305154 TI - Central Brown-Sequard syndrome caused by hyperextension: an unexpected complication of cervical pedicle screw fixation. PMID- 22305155 TI - Mainstem bronchus transection after blunt chest trauma. PMID- 22305156 TI - High seroprevalence of enterovirus infections in apes and old world monkeys. AB - To estimate population exposure of apes and Old World monkeys in Africa to enteroviruses (EVs), we conducted a seroepidemiologic study of serotype-specific neutralizing antibodies against 3 EV types. Detection of species A, B, and D EVs infecting wild chimpanzees demonstrates their potential widespread circulation in primates. PMID- 22305157 TI - TCFs and Wnt/beta-catenin signaling: more than one way to throw the switch. AB - Wnts are conserved, secreted signaling proteins that can influence cell behavior by stabilizing beta-catenin. Accumulated beta-catenin enters the nucleus, where it physically associates with T-cell factor (TCF) family members to regulate target gene expression in many developmental and adult tissues. Recruitment of beta-catenin to Wnt response element (WRE) chromatin converts TCFs from transcriptional repressors to activators. This review will outline the complex interplay between factors contributing to TCF repression and coactivators working with beta-catenin to regulate Wnt targets. In addition, three variations of the standard transcriptional switch model will be discussed. One is the Wnt/beta catenin symmetry pathway in Caenorhabditis elegans, where Wnt-mediated nuclear efflux of TCF is crucial for activation of targets. Another occurs in vertebrates, where distinct TCF family members are associated with repression and activation, and recent evidence suggests that Wnt signaling facilitates a "TCF exchange" on WRE chromatin. Finally, a "reverse switch" mechanism for target genes that are directly repressed by Wnt/beta-catenin signaling occurs in Drosophila cells. The diversity of TCF regulatory mechanisms may help to explain how a small group of transcription factors can function in so many different contexts to regulate target gene expression. PMID- 22305158 TI - Grainy head and its target genes in epithelial morphogenesis and wound healing. AB - The Grainy head (Grh) family of transcription factors is characterized by a unique DNA-binding domain that binds to a conserved consensus sequence. Nematodes and flies have a single grh gene, whereas mice and humans have evolved three genes encoding Grainy head-like (Grhl) factors. We review the biological function of Grh in different animals and the mechanisms modulating its activity. grh and grhl genes play a remarkably conserved role in epithelial organ development and extracellular barrier repair after tissue damage. Recent studies in flies and vertebrates suggest that Grh factors may be primary determinants of cell adhesion and epithelial tissue formation. Grh proteins can dimerize and act as activators or repressors in different developmental contexts. In flies, tissue-specific, alternative splicing generates different Grh isoforms with different DNA-binding specificities and functions. Grh activity is also modulated by receptor tyrosine kinases: it is phosphorylated by extracellular signal regulated kinase, and this phosphorylation is selectively required for epidermal barrier repair. Two mechanisms have been proposed to explain the repressive function of Grh on target gene transcription. First, Grh can target the Polycomb silencing complex to specific response elements. Second, it can directly compete for DNA binding with transcriptional activators. Understanding the molecular mechanisms of gene regulation by Grh factors is likely to elucidate phylogenetically conserved mechanisms of epithelial cell morphogenesis and regeneration upon tissue damage. PMID- 22305159 TI - Groucho: a corepressor with instructive roles in development. AB - Drosophila Groucho (Gro) is the founding member of a family of metazoan corepressors. Gro mediates repression through interactions with a myriad of DNA binding repressor proteins to direct the silencing of genes involved in many developmental processes, including neurogenesis and patterning of the main body axis, as well as receptor tyrosine kinase/Ras/MAPK, Notch, Wingless (Wg)/Wnt, and Decapentaplegic (Dpp) signaling. Gro mediates repression by multiple molecular mechanisms, depending on the regulatory context. Because Gro is a broadly expressed nuclear factor, whereas its repressor partners display restricted temporal and spatial distribution, it was presumed that this corepressor played permissive rather than instructive roles in development. However, a wide range of studies demonstrates that this is not the case. Gro can sense and integrate many cellular inputs to modulate the expression of variety of genes, making it a versatile corepressor with crucial instructive roles in development and signaling. PMID- 22305160 TI - Sparkling insights into enhancer structure, function, and evolution. AB - This review focuses on a single cis-regulatory element: the sparkling eye enhancer of the Drosophila dPax2 gene. sparkling responds to Notch and EGFR signaling, along with other direct regulatory inputs, to drive gene expression that is restricted to cone cells of the developing fly retina. Functional, genetic, biochemical, evolutionary, and bioinformatic analyses have revealed surprising properties of sparkling, which may provide new insights into cis regulatory logic and mechanisms of transcriptional activation. These properties include: a very high density of regulatory information and a correspondingly low "junk" content; an unexpectedly complex combinatorial code; tight functional constraints on enhancer organization, paradoxically coupled with high turnover of DNA sequence and binding site position; a requirement for weak binding of the transcription factor Su(H) to low-affinity sites in order to maintain a cell-type specific response to Notch signaling; and multiple specialized regulatory sequences conferring functionally distinct activation activities, all of which are required in concert to achieve proper gene expression in vivo. PMID- 22305161 TI - Computational strategies for the genome-wide identification of cis-regulatory elements and transcriptional targets. AB - Transcription factors (TFs) are key proteins that decode the information in our genome to express a precise and unique set of proteins and RNA molecules in each cell type in our body. These factors play a pivotal role in all biological processes, including the determination of a cell's fate during development and the maintenance of a cell's physiological function. To achieve this, a TF binds to specific DNA sequences in the noncoding part of the genome, recruits chromatin modifiers and cofactors, and directs the transcription initiation rate of its "target genes." Therefore, a key challenge in deciphering a transcriptional switch is to identify the direct target genes of the master regulators that control the switch, the cis-regulatory elements implementing (auto-)regulatory loops, and the target genes of all the TFs in the downstream regulatory network. A better knowledge of a TF's targetome during specification and differentiation of a particular cell type will generate mechanistic insight into its developmental program. Here, I review computational strategies and methods to predict transcriptional targets by genome-wide searches for TF binding sites using position weight matrices, motif clusters, phylogenetic footprinting, chromatin binding and accessibility data, enhancer classification, motif enrichment, and gene expression signatures. PMID- 22305162 TI - Transcriptional enhancers in ascidian development. AB - The study of cis-regulatory DNAs that control developmental gene expression is integral to the modeling of comprehensive genomic regulatory networks for embryogenesis. Ascidian embryos provide a unique opportunity for the analysis of cis-regulatory DNAs with cellular resolution in the context of a simple but typical chordate body plan. Here, we review landmark studies that have laid the foundations for the study of transcriptional enhancers, among other cis regulatory DNAs, and their roles in ascidian development. The studies using ascidians of the Ciona genus have capitalized on a unique electroporation technique that permits the simultaneous transfection of hundreds of fertilized eggs, which develop rapidly and express transgenes with little mosaicism. Current studies using the ascidian embryo benefit from extensively annotated genomic resources to characterize transcript models in silico. The search for functional noncoding sequences can be guided by bioinformatic analyses combining evolutionary conservation, gene coexpression, and combinations of overrepresented short-sequence motifs. The power of the transient transfection assays has allowed thorough dissection of numerous cis-regulatory modules, which provided insights into the functional constraints that shape enhancer architecture and diversification. Future studies will benefit from pioneering stable transgenic lines and the analysis of chromatin states. Whole genome expression, functional and DNA binding data are being integrated into comprehensive genomic regulatory network models of early ascidian cell specification with a single-cell resolution that is unique among chordate model systems. PMID- 22305164 TI - Temporal specification of neural stem cells: insights from Drosophila neuroblasts. AB - The mechanisms underlying the temporal specification of neural stem cells (NSCs), a process by which a single progenitor can generate different types of neurons and glia in an invariant order, are still poorly understood in mammals. However, in the past decade, work on Drosophila NSCs, called neuroblasts, has identified a series of sequentially expressed transcription factors that lies at the heart of this phenomenon. Here, I highlight some key findings that illuminate the role of these transcription factors during development and the regulatory principles allowing them not only to promote neuronal diversity but also to control the final number of neurons in the different regions of the nervous system. Ultimately, and given recent evidences of evolutionary conservation, cracking the temporal specification code of Drosophila neuroblasts may provide new perspectives for the safe manipulation of human NSCs and their therapeutic use. PMID- 22305163 TI - A dynamic network of morphogens and transcription factors patterns the fly leg. AB - Animal appendages require a proximodistal (PD) axis, which forms orthogonally from the two main body axes, anteroposterior and dorsoventral. In this review, we discuss recent advances that begin to provide insights into the molecular mechanisms controlling PD axis formation in the Drosophila leg. In this case, two morphogens, Wingless (Wg) and Decapentaplegic (Dpp), initiate a genetic cascade that, together with growth of the leg imaginal disc, establishes the PD axis. The analysis of cis-regulatory modules (CRMs) that control the expression of genes at different positions along the PD axis has been particularly valuable in dissecting this complex process. From these experiments, it appears that only one concentration of Wg and Dpp are required to initiate PD axis formation by inducing the expression of Distal-less (Dll), a homeodomain-encoding gene that is required for leg development. Once Dll is turned on, it activates the medially expressed gene dachshund (dac). Cross-regulation between Dll and dac, together with cell proliferation in the growing leg imaginal disc, results in the formation of a rudimentary PD axis. Wg and Dpp also initiate the expression of ligands for the EGFR pathway, which in turn induces the expression of a series of target genes that pattern the distal-most portion of the leg. PMID- 22305165 TI - Transcriptional switches direct plant organ formation and patterning. AB - Development of multicellular organisms requires specification of diverse cell types. In plants, development is continuous and because plant cells are surrounded by rigid cell walls, cell division and specification of daughter cell fate must be carefully orchestrated. During embryonic and postembryonic plant development, the specification of cell types is determined both by positional cues and cell lineage. The establishment of distinct transcriptional domains is a fundamental mechanism for determining different cell fates. In this review, we focus on four examples from recent literature of switches operating in cell fate decisions that are regulated by transcriptional mechanisms. First, we highlight a transcriptional mechanism involving a mobile transcription factor in formation of the two ground tissue cell types in roots. Specification of vascular cell types is then discussed, including new details about xylem cell-type specification via a mobile microRNA. Next, transcriptional regulation of two key embryonic developmental events is considered: establishment of apical-basal polarity in the single-celled zygote and specification of distinct root and shoot stem cell populations in the plant embryo. Finally, a dynamic transcriptional mechanism for lateral organ positioning that integrates spatial and temporal information into a repeating pattern is summarized. PMID- 22305166 TI - Transcriptional control of cell fate specification: lessons from the fly retina. AB - It is now widely recognized that as cells of developing tissues transition through successive states of decreasing pluripotency into a state of terminal differentiation, they undergo significant changes in their gene expression profiles. Interestingly, these successive states of increasing differentiation are marked by the spatially and temporally restricted expression of sets of transcription factors. Each wave of transcription factors not only signals the arrival of a given stage in cellular differentiation, but it is also necessary for the activation of the next set of transcription factors, creating the appearance of a smooth, directed, and deterministic genetic program of cellular differentiation. Until recently, however, it was largely unknown which genes, besides each other, these transcription factors were activating. Thus, the molecular definition of any given step of differentiation, and how it gave rise to the following step remained unclear. Recent advances in transcriptomics, bioinformatics, and molecular genetics resulted in the identification of numerous transcription factor target genes (TGs). These advances have opened the door to using similar approaches in developmental biology to understand what the transcriptional cascades of cellular differentiation might be. Using the development of the Drosophila eye as a model system, we discuss the role of transcription factors and their TGs in cell fate specification and terminal differentiation. PMID- 22305167 TI - Diversification of muscle types in Drosophila: upstream and downstream of identity genes. AB - Understanding gene regulatory pathways underlying diversification of cell types during development is one of the major challenges in developmental biology. Progressive specification of mesodermal lineages that are at the origin of body wall muscles in Drosophila embryos has been extensively studied during past years, providing an attractive framework for dissecting cell type diversification processes. In particular, it has been found that muscle founder cells that are at the origin of individual muscles display specific expression of transcription factors that control diversification of muscle types. These factors, encoded by genes collectively called muscle identity genes, are activated in discrete subsets of muscle founders. As a result, each founder cell is thought to carry a unique combinatorial code of identity gene expression. Considering this, to define temporally and spatially restricted expression of identity genes, a set of coordinated upstream regulatory inputs is required. But also, to realize the identity program and to form specific muscle types with distinct properties, an efficient battery of downstream identity gene targets needs to be activated. Here we review how the specificity of expression and action of muscle identity genes is acquired. PMID- 22305168 TI - Transcriptional switches during development. Preface. PMID- 22305169 TI - Flaxseed dietary fibers lower cholesterol and increase fecal fat excretion, but magnitude of effect depend on food type. AB - BACKGROUND: Dietary fibers have been proposed to play a role in cardiovascular risk as well as body weight management. Flaxseeds are a good source of dietary fibers, and a large proportion of these are water-soluble viscous fibers. METHOD: Here, we examine the effect of flaxseed dietary fibers in different food matrices on blood lipids and fecal excretion of fat and energy in a double-blind randomized crossover study with 17 subjects. Three different 7-d diets were tested: a low-fiber control diet (Control), a diet with flaxseed fiber drink (3/day) (Flax drink), and a diet with flaxseed fiber bread (3/day) (Flax bread). Total fat and energy excretion was measured in feces, blood samples were collected before and after each period, and appetite sensation registered 3 times daily before main meals. RESULTS: Compared to control, Flax drink lowered fasting total-cholesterol and LDL-cholesterol by 12 and 15%, respectively, (p < 0.01), whereas Flax bread only produced a reduction of 7 and 9%, respectively (p < 0.05). Fecal fat and energy excretion increased by 50 and 23% with Flax drink consumption compared to control (p < 0.05), but only fecal fat excretion was increased with Flax bread compared to control (p < 0.05). CONCLUSION: Both Flax drink and Flax bread resulted in decreased plasma total and LDL-cholesterol and increased fat excretion, but the food matrix and/or processing may be of importance. Viscous flaxseed dietary fibers may be a useful tool for lowering blood cholesterol and potentially play a role in energy balance. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00953004. PMID- 22305170 TI - gamma-Glutamyl transpeptidase from Bacillus pumilus KS 12: decoupling autoprocessing from catalysis and molecular characterization of N-terminal region. AB - Gamma glutamyl transpeptidase from Bacillus pumilus KS12 (GGTBP) was cloned, expressed in pET-28-E. coli expression system as a heterodimeric enzyme with molecular weights of 45 and 20 kDa for large and small subunit, respectively. It was purified by nickel affinity chromatography with hydrolytic and transpeptidase activity of 1.82 U/mg and 4.35 U/mg, respectively. Sequence analysis revealed that GGTBP was most closely related to Bacillus licheniformis GGT and had all the catalytic residues and nucleophiles for autoprocessing recognized from E. coli. It was optimally active at pH 8 and 60 degrees C. It exhibited pH stability from pH 6-9 and high thermostability with t(1/2) of 15 min at 70 degrees C. It had K(m), V(max) of 0.045 mM, 4.35 MUmol/mg/min, respectively. Decoupling of autoprocessing by co-expressing large and small subunit in pET-Duet1-E. coli expression system yielded active enzyme with transpeptidase activity of 5.31 U/mg. Though N-terminal truncations of rGGTBP upto 95 aa did not affect autoprocessing of GGT however activity was lost with truncation beyond 63 aa. PMID- 22305171 TI - Continuous lactose fermentation by Clostridium acetobutylicum--assessment of energetics and product yields of the acidogenesis. AB - An assessment of both the growth and the metabolism of acidogenic cells Clostridium acetobutylicum DSM 792 is reported in the paper. Tests were carried out in a CSTR under controlled pH conditions. Cultures were carried out using a semi-synthetic medium supplemented with lactose as carbon source. Acids and solvents, that represent products of the ABE process, have been purposely added in controlled amounts to the culture medium to investigate their effects on the product yields. The mass fractional yield of biomass and products were expressed as a function of the specific growth rate taking into account the Pirt model. The maximum ATP yield and the maintenance resulted 29.1 g(DM)/mol(ATP) and 0.012 mol(ATP)/g(DM)h, respectively. Quantitative features of the C. acetobutylicum growth model were in good agreement with experimental results. The model proposes as a tool to estimate the mass fractional yield even for fermentations carried out under conditions typical of the solventogenesis. PMID- 22305172 TI - Production of human papillomavirus type 33 L1 major capsid protein and virus-like particles from Bacillus subtilis to develop a prophylactic vaccine against cervical cancer. AB - We developed a bacterial expression system to produce human papillomavirus (HPV) type 33 L1 major capsid protein and virus-like particles from a recombinant Bacillus subtilis strain. For the first time, we have isolated self-assembled virus-like particles (VLPs) of HPV type 33 from B. subtilis, a strain generally recognized as safe (GRAS). The gene encoding the major capsid protein L1 of HPV type 33 was amplified from viral DNA isolated from a Korean patient and expressed in B. subtilis; a xylose-induction system was used to control gene activity. HPV33 L1 protein was partially purified by 40% (w/v) sucrose cushion centrifugation and strong cation exchange column chromatography. Eluted samples exhibited immunosignaling in fractions of 0.5-1.0 M NaCl. The HPV33 L1 protein was shown to be approximately 56 kDa in size by SDS-PAGE and Western blotting; recovery and purity were quantified by indirect immuno-ELISA assay. The final yield and purity were approximately 20.4% and 10.3%, respectively. Transmission electron microscopic analysis of fractions immunoactive by ELISA revealed that the L1 protein formed self-assembled VLPs with a diameter of approximately 20-40 nm. Humoral and cellular immune responses provoked by the B. subtilis/HPV33 L1 strain were approximately 100- and 3-fold higher than those of the empty B. subtilis strain as a negative control, respectively. Development of a VLP production and delivery system using B. subtilis will be helpful, in that the vaccine may be convenient production as an antigen delivery system. VLPs thus produced will be safer for human use than those purified from Gram-negative strains such as Escherichia coli. Also, use of B. subtilis as a host may aid in the development of either live or whole cell vaccines administered by antigen delivery system. PMID- 22305173 TI - A mediated glucose/oxygen enzymatic fuel cell based on printed carbon inks containing aldose dehydrogenase and laccase as anode and cathode. AB - Enzyme electrodes show great potential for many applications, as biosensors and more recently as anodes and cathodes in biocatalytic fuel cells for power generation. Enzymes have advantages over metal catalysts, as they provide high specificity and reaction rates, while operating under mild conditions. Here we report on studies related to development of mass-producible, completely enzymatic printed glucose/oxygen biofuel cells. The cells are based on filter paper coated with conducting carbon inks containing mediators and laccase, for reduction of oxygen, or aldose dehydrogenase, for oxidation of glucose. Mediator performance in these printed formats is compared to relative rate constants for the enzyme mediator reaction in solution, for a range of anode and cathode mediators. The power output and stability of fuels cells using an acidophilic laccase isolated from Trametes hirsuta is greater, at pH 5, than that for cells based on Melanocarpus albomyces laccase, that shows optimal activity closer to neutral pH, at pH 6. Highest power output, although of limited stability, was observed for ThL/ABTS cathodes, providing a maximum power density of 3.5 MUWcm(-2) at 0.34 V, when coupled to an ALDH glucose anode mediated by an osmium complex. The stability of cell voltage above a threshold of 200 mV under a moderate 75 kOmega load is used to benchmark printed fuel cell performance. Highest stability was obtained for a printed fuel cell using osmium complexes as mediators of glucose oxidation by aldose dehydrogenase, and oxygen reduction by T. hirsuta laccase, maintaining cell voltage above 200 mV for 137 h at pH 5. These results provide promising directions for further development of mass-producible, completely enzymatic, printed biofuel cells. PMID- 22305174 TI - Synthesis of galacto-oligosaccharides by beta-galactosidase from Aspergillus oryzae using partially dissolved and supersaturated solution of lactose. AB - The effect of enzyme to substrate ratio, initial lactose concentration and temperature has been studied for the kinetically controlled reaction of lactose transgalactosylation with Aspergillus oryzae beta-galactosidase, to produce prebiotic galacto-oligosaccharides (GOS). Enzyme to substrate ratio had no significant effect on maximum yield and specific productivity. Galacto oligosaccharide syntheses at very high lactose concentrations (40, 50 and 60%, w/w, lactose monohydrate) were evaluated at different temperatures (40, 47.5 and 55 degrees C). Within these ranges, lactose could be found as a supersaturated solution or a heterogeneous system with precipitated lactose, resulting in significant effect on GOS synthesis. An increase in initial lactose concentration produced a slight increase in maximum yield as long as lactose remained dissolved. Increase in temperature produced a slight decrease in maximum yield and an increase in specific productivity when supersaturation of lactose occurred during reaction. Highest yield of 29 g GOS/100 g lactose added was obtained at a lactose monohydrate initial concentration of 50% (w/w) and 47.5 degrees C. Highest specific productivity of 0.38 g GOSh(-1) mg enzyme(-1) was obtained at lactose monohydrate initial concentration of 40% (w/w) and 55 degrees C, where a maximum yield of 27 g GOS/100 g lactose added was reached. This reflects the complex interplay between temperature and initial lactose concentration on the reaction of synthesis. When lactose precipitation occurred, values of yields and specific productivities lower than 22 g GOS/100 g lactose added and 0.03 gGOSh( 1) mg enzyme(-1) were obtained, respectively. PMID- 22305175 TI - The adsorption and enzyme activity profiles of specific Trichoderma reesei cellulase/xylanase components when hydrolyzing steam pretreated corn stover. AB - Recycling of enzymes during biomass conversion is one potential strategy to reduce the cost of the hydrolysis step of cellulosic ethanol production. Devising an efficient enzyme recycling strategy requires a good understanding of how the enzymes adsorb, distribute, and interact with the substrate during hydrolysis. We investigated the interaction of individual Trichoderma reesei enzymes present in a commercial cellulase mixture during the hydrolysis of steam-pretreated corn stover (SPCS). The enzyme profiles were followed using zymograms, gel electrophoresis, enzyme activity assays and mass spectrometry. The adsorption and activity profiles of 6 specific enzymes Cel7A (CBH I), Cel7B (EG I), Cel5A (EG II), Xyn 10 (endo-1,4-beta-xylanase III), Xyn 11 (endo-xylanase II), and beta glucosidase were characterized. Initially, each of the enzymes rapidly adsorbed onto the SPCS. However, this was followed by partial desorption to an adsorption equilibrium where the Cel7A, Cel7B, Xyn 10, and beta-glucosidase were partially adsorbed to the SPCS and also found free in solution throughout the course of hydrolysis. In contrast, the Cel5A and Xyn 11 components remained primarily free in the supernatant. The Cel7A component also exhibited a partial desorption when the rate of hydrolysis leveled off as evidenced by MUC zymogram and SDS-PAGE. Those cellulase components that did not bind to the substrate were generally less stable and lost their activities within the first 24h when compared to enzymes that were distributed in both the liquid and solid phases. Therefore, to ensure maximum enzyme activity recovery, enzyme recycling seems to be most effective when short-term rounds of hydrolysis are combined with the recovery of enzymes from both the liquid and the solid phases and potentially enzyme supplementation to replenish lost activity. PMID- 22305176 TI - Chemical kinetics and interactions involved in horseradish peroxidase-mediated oxidative polymerization of phenolic compounds. AB - The primary objective of this research was to evaluate various factors that affect the reaction rate of oxidative coupling (OXC) reaction of phenolic estrogens catalyzed by horseradish peroxidase (HRP). Kinetic parameters were obtained for the conversion of phenol as well as natural and synthetic estrogens estrone (E(1)), 17beta-estradiol (E(2)), estriol (E(3)), and 17alpha ethinylestradiol (EE(2)). Molecular orbital theory and Autodock software were employed to analyze chemical properties and substrate binding characteristics. Reactions were first order with respect to phenolic concentration and reaction rate constants (k(r)) were determined for phenol, E(3), E(1), E(2) and EE(2) (in increasing order). Oxidative coupling was controlled by enzyme-substrate interactions, not collision frequency. Docking simulations show that higher binding energy and a shorter binding distance both promote more favorable kinetics. This research is the first to show that the OXC of phenolics is an entropy-driven and enthalpy-retarded process. PMID- 22305177 TI - Clonal spread of Mycoplasma pneumoniae in primary school, Bordeaux, France. PMID- 22305179 TI - [Solitary rectal diverticulum. A case presentation]. PMID- 22305180 TI - Direction of innervation after interpositional nerve graft between facial and hypoglossal nerves in individuals with or without facial palsy: a rat model for treating incomplete facial palsy. AB - BACKGROUND: The use of an interpositional nerve graft (IPNG) between the facial and hypoglossal nerves for incomplete facial palsy has recently been reported. However, its mechanism has not been elucidated. We established a rat model of IPNG to study incomplete facial palsy and confirmed the direction of innervation through the grafted nerve with or without facial nerve injury. METHODS: Twenty rats were divided into five groups (n = 4): a control group (group A), an incomplete facial palsy group (group B), an IPNG-treated group (group C), an incomplete facial palsy group treated with IPNG (group D) and an incomplete hypoglossal nerve palsy group treated with IPNG (group E). After surgery, mimetic muscle movement was evaluated using an original scoring system. Twelve weeks after surgery, the mimetic muscles of the tongue were injected with Fast Blue and DiI. Retrograde-labelled neurons were counted through the facial and hypoglossal nuclei, and mimetic muscle specimens stained with Masson's trichrome were examined. RESULTS: Fast Blue-labelled neurons were noted in the hypoglossal nucleus in groups C and D, and DiI-labelled neurons within the facial nucleus were noted in groups C and E. The group D facial palsy score statistically exceeded the group B score. CONCLUSIONS: The results revealed that axonal regeneration through IPNG is bi-directional and is preferentially directed towards the injured side. Innervation from the hypoglossal nerve to mimetic muscles through IPNG prevents muscle atrophy and helps counter facial palsy. PMID- 22305181 TI - Fates of murine pluripotent stem cell-derived neural progenitors following transplantation into mouse cochleae. AB - This study evaluated the tumorigenesis risk of induced pluripotent stem (iPS) cells after transplantation into the cochlea. One mouse embryonic stem (ES) cell line and three mouse iPS cell lines, one derived from adult mouse tail-tip fibroblasts (TTFs) and two from mouse embryonic fibroblasts (MEFs), were neurally induced by stromal cell-inducing activity. Before transplantation, the efficiency of neural induction and the proportion of residual undifferentiated cells were evaluated using immunocytochemistry, and no significant differences were observed in the ratios of colonies expressing betaIII tubulin, nestin, or octamer (Oct)3/4. Four weeks after transplantation into the cochleae of neonatal mice, the number of surviving transplants of TTF-derived iPS cells generated by retroviral infection was significantly higher than those of MEF-derived iPS cells generated by plasmid transfection. Teratoma formation was identified in one of five cochleae transplanted with TTF-derived iPS cells. However, no significant differences were found in the cell proliferation activity or the extent of differentiation into mature neurons among the cell lines. These findings emphasize the necessity of selecting appropriate iPS cell lines and developing methods to eliminate undifferentiated cells after neural induction, in order to establish safe iPS cell-based therapy for the inner ear. PMID- 22305182 TI - Aromatherapy massage seems to enhance relaxation in children with burns: an observational pilot study. AB - OBJECTIVE: This observational pilot study investigated effects of aromatherapy massage in paediatric burn patients. METHODS: The setting was a 17 beds level I burn unit in Cape Town, South Africa. Between January and October 2009 heart rates and respiratory rates of patients who underwent aromatherapy massage sessions were read before and after the sessions. Primary outcomes were decline in heart rates and respiratory rates, a sign of relaxation. Behavioural responses (sleep/awake state, facial expression, body posture) were documented as secondary outcomes. RESULTS: A convenience sample of 71 paediatric burn patients (median age 3 years) underwent a total of 126 massage sessions. Mean heart rate decreased significantly from 118 (SD 20) to 109 (SD 21), t=9.8, p<0.001. Mean respiratory rate decreased significantly from 34 (SD 8) to 30 (SD 8), t=10.2, p<0.001. Most massage sessions (92.8%) elicited positive behaviour to the massage, e.g. the child fell asleep, calmed or asked to continue. Nine patients (7.2%) with a median age of 15 months who underwent a single massage session did not show positive behaviour but cried, wriggled or were distressed. CONCLUSIONS: Aromatherapy massage seems to be a helpful nonpharmacological approach to reduce hospitalized paediatric burn patients' distress. Future studies with better research designs and validated outcome measures should confirm our findings. PMID- 22305183 TI - Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol. AB - BACKGROUND: Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. METHODS/DESIGN: We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. DISCUSSION: Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials. TRIAL REGISTRATION: Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18. PMID- 22305184 TI - Displaced paediatric distal radius fractures--when should we use percutaneous wires? AB - PURPOSE: To establish the intra-operative radiographic parameters that predict the need for percutaneous wire fixation to prevent redisplacement following manipulation for displaced paediatric distal radius fractures. MATERIALS AND METHODS: A retrospective study of 105 children, assessing pre-, intra- and post operative radiographs. Optimal reduction was defined as less than 10% residual translation and less than 5 degrees of angulation on anteroposterior and lateral radiographs. Redisplacement was defined as more than 20 degrees angulation or 50% translation on either view. RESULTS: No fracture that was optimally reduced redisplaced. 40% of fractures with suboptimal reduction redisplaced. Initial translation was significantly associated with redisplacement. CONCLUSIONS: If our criteria for optimal reduction are met, closed reduction and casting can be confidently employed. If not, percutaneous wires should be employed to avoid redisplacement, especially in cases with a high grade of initial translation. PMID- 22305185 TI - Multiorgan dysfunction caused by travel-associated African trypanosomiasis. AB - We describe a case of multiorgan dysfunction secondary to Trypanosoma brucei rhodesiense infection acquired on safari in Zambia. This case was one of several recently reported to ProMED-mail in persons who had traveled to this region. Trypanosomiasis remains rare in travelers but should be considered in febrile patients who have returned from trypanosomiasis-endemic areas of Africa. PMID- 22305186 TI - Effects of omega-3 fatty acids on cognitive performance: a meta-analysis. AB - BACKGROUND: Higher intake of omega-3 fatty acids (n-3 FAs) is associated with a reduced risk of Alzheimer's disease (AD) and milder forms of cognitive impairment (e.g. cognitive impairment no dementia [CIND]); however, findings from interventional trials are inconsistent. This meta-analysis examined the neuropsychological benefit of n-3 FAs in randomized double-blind placebo controlled studies (RCTs) including healthy, CIND, or AD subjects. METHODS: Literature was searched using Medline, Embase, PsycInfo, Cochrane Library, Allied and Complementary Medicine Database (AMED), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) up to September 2011. Treatment effects were summarized across cognitive subdomains, and effect sizes were estimated using Hedge's g and random effects modeling. RESULTS: Ten RCTs were combined quantitatively. There was no effect of n-3 FAs on composite memory (g = 0.04 [95% CI: -0.06-0.14], N = 934/812, p = 0.452). When examined by domain, no overall benefit for immediate recall (0.04 [-0.05-0.13], N = 934/812, p = 0.358) was detected; however, an effect in CIND subjects (0.16 [0.01-0.31], N = 349/327, p = 0.034) was found. A benefit for attention and processing speed was also detected in CIND (0.30 [0.02-0.57], N = 107/86, p = 0.035), but not healthy subjects. Benefits for delayed recall, recognition memory, or working memory and executive function were not observed. Treatment did not benefit AD patients as measured by the Mini-Mental State Examination (MMSE) or Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog). No differences in adverse events (AE), dropout, or dropout due to AE between groups were observed. CONCLUSIONS: These results suggest an effect of n-3 FAs within specific cognitive domains in CIND, but not in healthy or AD subjects. PMID- 22305187 TI - Alleles that modulate late life hearing in genetically heterogeneous mice. AB - A genetically heterogeneous population of mice was tested for hearing at 8, 18, and 22 months by auditory brainstem response (ABR), and genotyped at 128 markers to identify loci that modulate late life hearing loss. Half of the test mice were exposed to noise for 2 hours at age 20 months. Polymorphisms affecting hearing at 18 months were noted on chromosomes 2, 3, 7, 10, and 15. Most of these loci had effects only on responses to 48 kHz stimuli, but a subset also influenced the auditory brainstem response at lower frequencies. Loci on chromosomes 4, 10, 12, and 14 had significant effects on hearing at 22 months in noise-exposed mice, and loci on chromosomes 10 and 11 had effects on mice not exposed to noise. Outer hair cell loss was modulated by polymorphisms on chromosomes 10, 11, 12, 17, and 19. Resistance to age-related hearing loss is thus modulated by a set of genetic effects, some age-specific, some frequency specific, some dependent on prior exposure to noise, and some of which compromise survival of cochlear hair cells. PMID- 22305188 TI - The Complementary Medicine Education and Outcomes (CAMEO) program: a foundation for patient and health professional education and decision support programs. AB - OBJECTIVE: This paper describes the background, design and evaluation of a theory informed education and decision support program for cancer patients considering complementary medicine (CM). METHODS: The program was informed by the Shared Decision Making theory, the Ottawa Decision Support Framework and the Supportive Care Framework. Previous empirical evidence and baseline research were used to identify patients' and health professionals' (HPs) information and decision support needs related to CM. RESULTS: To address the continuum of CM needs, a variety of education and decision support interventions were developed, including basic CM information and resources for patients and HPs, a group education program and one-on-one decision support coaching for patients, and an on-line education module for HPs. Evaluation of the program and individual interventions is underway. CONCLUSIONS: This education and decision support program addresses a significant gap in care and offers an evidence-informed framework in which to translate CM evidence to conventional care settings and promote communication about CM. PRACTICE IMPLICATIONS: Evidence-informed CM education and decision support interventions are needed to shift the culture around CM within conventional care settings and promote open communication that will lead to CM therapies being safely integrated into care. PMID- 22305189 TI - PhosphoRice: a meta-predictor of rice-specific phosphorylation sites. AB - BACKGROUND: As a result of the growing body of protein phosphorylation sites data, the number of phosphoprotein databases is constantly increasing, and dozens of tools are available for predicting protein phosphorylation sites to achieve fast automatic results. However, none of the existing tools has been developed to predict protein phosphorylation sites in rice. RESULTS: In this paper, the phosphorylation site predictors, NetPhos 2.0, NetPhosK, Kinasephos, Scansite, Disphos and Predphosphos, were integrated to construct meta-predictors of rice specific phosphorylation sites using several methods, including unweighted voting, unreduced weighted voting, reduced unweighted voting and weighted voting strategies. PhosphoRice, the meta-predictor produced by using weighted voting strategy with parameters selected by restricted grid search and conditional random search, performed the best at predicting phosphorylation sites in rice. Its Matthew's Correlation Coefficient (MCC) and Accuracy (ACC) reached to 0.474 and 73.8%, respectively. Compared to the best individual element predictor (Disphos_default), PhosphoRice archieved a significant increase in MCC of 0.071 (P < 0.01), and an increase in ACC of 4.6%. CONCLUSIONS: PhosphoRice is a powerful tool for predicting unidentified phosphorylation sites in rice. Compared to the existing methods, we found that our tool showed greater robustness in ACC and MCC. PhosphoRice is available to the public at http://bioinformatics.fafu.edu.cn/PhosphoRice. PMID- 22305190 TI - Pedometers for all! PMID- 22305191 TI - Polysaccharide peptides from Coriolus versicolor competitively inhibit model cytochrome P450 enzyme probe substrates metabolism in human liver microsomes. AB - Polysaccharide peptide (PSP), isolated from COV-1 strain of Coriolus versicolor, is commonly used as an adjunct in cancer chemotherapy or health supplement in China. Previous studies have shown that PSP decreased antipyrine clearance and inhibited rat CYP2C11-mediated tolbutamide 4-hydroxylation and in human CYP2C9. In this study, the effects of the water extractable fraction of PSP on the metabolism of model CYP1A2, CYP2D6, CYP2E1 and CYP3A4 probe substrates were investigated in pooled human liver microsomes. PSP (1.25-20MUM) dose-dependently decreased CYP1A2-mediated metabolism of phenacetin to paracetamol (IC(50) 19.7MUM) and CYP3A4-mediated metabolism of testosterone to 6beta hydroxytestosterone (IC(20) 7.06MUM). Enzyme kinetics studies showed the inhibition of CYP1A2 activity was competitive and concentration-dependent (K(i)=18.4MUM). Inhibition of testosterone to 6beta-hydroxytestosterone was also competitive and concentration-dependent (K(i)=31.8MUM). Metabolism of dextromethorphan to dextrorphan (CYP2D6-mediated) and chlorzoxazone to 6 hydroxychlorzoxazone (CYP2E1-mediated) was only minimally inhibited by PSP, with IC(20) values at 15.6MUM and 11.9MUM, respectively. This study demonstrated that PSP competitively inhibited the CYP1A2- and CYP3A4-mediated metabolism of model probe substrates in human liver microsomes in vitro. The relatively high K(i) values for CYP1A2 and CYP3A4 would suggest a low potential for PSP to cause herb drug interaction related to these CYP isoforms. PMID- 22305192 TI - Ozone oxidation and aerobic biodegradation with spent mushroom compost for detoxification and benzo(a)pyrene removal from contaminated soil. AB - The combination of ozonation and spent mushroom compost (SMC)-mediated aerobic biological treatment was investigated in the removal of benzo(a)pyrene from contaminated soil. The performances of the process alone and combined were evaluated in terms of benzo(a)pyrene removal efficiency, mineralization efficiency (as total organic carbon removal), and soil residual toxicity (phytotoxicity to Lepidium Sativum and toxicity to Vibrio fischeri). In spite of the removal efficiency (35%) obtained by SMC-mediated biological process as a stand-alone treatment, the combined process showed a benzo(a)pyrene concentration reduction higher than 75%; the best removal (82%) was observed after 10 min pre ozonation treatment. In particular, ozonation improved the biodegradability of the contaminant, as confirmed by the increase of CO(2) production (close to 70% compared to the control), mineralization (greater than 60%) and bacterial density (which increased by two orders of magnitude). Moreover, according to phytotoxicity tests on L. Sativum, the aerobic biological process of pre-ozonated soil decreased toxicity. According to the results achieved in the present study, ozonation pre-treatment showed an high potential to overcome the limitation of bioremediation of recalcitrant compound, but it should be carefully operated in order to maximize PAH removal efficiency as well as to minimize soil residual toxicity which can result from the formation of the oxidation intermediates. PMID- 22305193 TI - Investigations on the interaction of the phototoxic alkaloid coralyne with serum albumins. AB - The interaction of the phototoxic alkaloid coralyne with bovine and human serum albumins (BSA, HSA) was investigated. Absorbance and fluorescence quenching experiments revealed the formation of strong complexes. Based on the binding parameters calculated from Stern-Volmer quenching method, coralyne has higher affinity to BSA (~10(5) M(-1)) compared to HSA (~10(4) M(-1)). Forster resonance energy transfer studies showed that the specific binding distances between Trp (donor) of the proteins and coralyne (acceptor) were 2.95 and 3.10 nm, respectively. The bindings were favored by negative enthalpy and a stronger favorable entropy contribution. The heat capacity values for binding to BSA and HSA were similar, indicating the involvement of similar molecular forces in the complexation. Competitive binding experiments using site markers demonstrated that coralyne binds to site I (subdomain IIA) of both proteins. The secondary structure of the proteins was altered, suggesting a small but definitive partial unfolding on complexation. PMID- 22305194 TI - Risk for emergence of dengue and chikungunya virus in Israel. PMID- 22305195 TI - Training health professionals in shared decision-making: an international environmental scan. AB - OBJECTIVE: To identify and analyze training programs in shared decision-making (SDM) for health professionals. METHODS: We conducted an environmental scan looking for programs that train health professionals in SDM. Pairs of reviewers independently analyzed the programs identified using a standardized data extraction sheet. The developers of the programs validated the data extracted. RESULTS: We identified 54 programs conducted between 1996 and 2011 in 14 countries and 10 languages. Thirty-four programs targeted licensed health professionals, 10 targeted pre-licensure health professionals, and 10 targeted both. Most targeted only the medical profession (n=32); six targeted more than one health profession. The five most frequently mentioned teaching methods were case-based discussion, small group educational session, role play, printed educational material, and audit and feedback. Thirty-six programs reported having evaluated their impacts but evaluation data was available only for 17. CONCLUSIONS: Health professional training programs in SDM vary widely in how and what they deliver, and evidence of their effectiveness is sparse. PRACTICE IMPLICATIONS: This study suggests there is a need for international consensus on ways to address the variability in SDM training programs. We need agreed criteria for certifying the programs and for determining the most effective types of training. PMID- 22305196 TI - Patients' understanding of prescription instructions in a semi-urban setting in Cameroon. AB - OBJECTIVE: This cross-sectional study investigates the factors associated with patient comprehension of frequently used prescription patterns and explores patients' preferences for the various methods. METHODS: We interviewed two hundred and four consenting patients selected consecutively from the waiting rooms of the St. Elizabeth Catholic Hospital-Shisong in the north west region of Cameroon. We recorded socio-demographic data and their understanding and preference for four prescription modalities: pictograms, written out, symbols and Latin abbreviations. We studied the relationship between these variables in a logistic multivariate analysis. RESULTS: Understanding was best with symbols (89.7%) and worst when Latin abbreviations (26.9%) were used. Higher levels of education were associated with better understanding of Latin abbreviations (OR 18.87; 95% CI 2.44-142.86), written out prescriptions (OR 58.82; 95% CI 23.25 333.33), symbols (OR 1.47; 95% CI 4.25-50.00) and pictograms (OR 52.63; 92% CI 1.85-142.86) after controlling for confounding. Participants mostly preferred pictograms (40.7%) and written-out prescriptions (30.9%). CONCLUSION: Latin abbreviations were the most difficult to understand and should no longer be used. Symbols are more easily understood. PRACTICE IMPLICATIONS: Latin abbreviations should be discouraged. Symbols are better, especially for patients with low levels of education. Prescribing using pictograms and plain text may facilitate understanding in this setting. PMID- 22305197 TI - Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects. AB - BACKGROUND: High dose oral thiamine may have a role in treating diabetes, heart failure, and hypermetabolic states. The purpose of this study was to determine the pharmacokinetic profile of oral thiamine hydrochloride at 100 mg, 500 mg and 1500 mg doses in healthy subjects. METHODS: This was a randomized, double-blind, single-dose, 4-way crossover study. Pharmacokinetic measures were calculated. RESULTS: The AUC0-10 hr and C(max) values increased nonlinearly between 100 mg and 1500 mg. The slope of the AUC0-10 hr vs dose, as well as the C(max) vs dose, plots are steepest at the lowest thiamine doses. CONCLUSION: Our study demonstrates that high blood levels of thiamine can be achieved rapidly with oral thiamine hydrochloride. Thiamine is absorbed by both an active and nonsaturable passive process. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00981877. PMID- 22305198 TI - [Primary vasculitis of the central nervous system: a diagnostic and therapeutic challenge]. PMID- 22305199 TI - [May-Thurner syndrome: an infrequent cause of spontaneous left iliac vein rupture]. PMID- 22305200 TI - [Pretracheal brachiocephalic trunk]. PMID- 22305201 TI - Reuse of steel slag in bituminous paving mixtures. AB - This paper presents a comprehensive study to evaluate the mechanical properties and environmental suitability of electric arc furnace (EAF) steel slag in bituminous paving mixtures. A variety of tests were executed on samples of EAF slag to characterize the physical, geometrical, mechanical and chemical properties as required by UNI EN specifications, focusing additionally on the volumetric expansion associated with hydration of free CaO and MgO. Five bituminous mixtures of aggregates for flexible road pavement were designed containing up to 40% of EAF slag and were tested to determine Marshall stability and indirect tensile strength. The leaching behaviour of slag samples and bituminous mixtures was evaluated according to the UNI EN leaching test. The tested slag showed satisfactory physical and mechanical properties and a release of pollutants generally below the limits set by the Italian code. Tests on volume stability of fresh materials confirmed that a period of 2-3 months is necessary to reduce effects of oxides hydration. The results of tests performed on bituminous mixtures with EAF slag were comparable with the performance of mixtures containing natural aggregates and the leaching tests provided satisfactory results. PMID- 22305202 TI - Access the toxic effect of the antibiotic cefradine and its UV light degradation products on two freshwater algae. AB - Two common freshwater algae Microcystis aeruginosa and Scenedesmus obliquus were employed as test organism to evaluate the toxic effects of the widely used antibiotic, cefradine. In general, cefradine had significantly toxic effect on population growth and chlorophyll-a accumulation of two algae and the cyanophyceae was more sensitive than the chlorophyceae. In addition, cefradine UV light degraded products had adverse effect on M. aeruginosa's growth and chlorophyll-a accumulation. In comparison, even if S. obliquus had growth ability when exposed to cefradine UV light-degradation products, the algal photosynthesis function was also disrupted. PMID- 22305203 TI - Per- and polyfluoroalkyl substances in snow, lake, surface runoff water and coastal seawater in Fildes Peninsula, King George Island, Antarctica. AB - The multi-matrices samples from snow (n=4), lake water (n=4), surface runoff water (SRW) (n=1) and coastal seawater (n=10) were collected to investigate the spatial distribution and the composition profiles of per- and polyfluoroalkyl substances (PFASs) in Fildes Peninsula, King George Island, Antarctica in 2011. All samples were prepared by solid-phase extraction and analyzed by using high performance liquid chromatography/negative electrospray ionization-tandem mass spectrometry (HPLC/(-)ESI-MS/MS). 14 PFASs in snow, 12 PFASs in lake water, 9 PFASs in SRW and 13 PFASs in coastal seawater were quantified, including C(4), C(7), C(8), C(10) PFSAs, C(4)-C(9), C(11)-C(14), C(16) PFCAs, and FOSA. PFOA was detected in all samples with the highest concentration (15,096 pg/L) in coastal seawater indicating a possible influence of local sewage effluent. High concentration and mostly frequency of PFBA occurred in snow (up to 1112 pg/L), lake water (up to 2670 pg/L) and SRW (1431 pg/L) while detected in the range of method detection limited (MDL) in the coastal seawaters indicate that PFBA is mainly originated from atmospheric dust contamination and also affected by the degradation of their precursors. No geographical differences in PFOS concentrations (n=8, 18 +/- 3 pg/L) were measured in all snow and lake water samples also suggests that PFOS could be originated from the degradation of their precursors which can transported by long-range atmospheric route, but in a very low level. PMID- 22305204 TI - Phylogeography of Francisella tularensis subsp. holarctica, Europe. AB - Francisella tularensis subsp. holarctica isolates from Austria, Germany, Hungary, Italy, and Romania were placed into an existing phylogeographic framework. Isolates from Italy were assigned to phylogenetic group B.FTNF002-00; the other isolates, to group B.13. Most F. tularensis subsp. holarctica isolates from Europe belong to these 2 geographically segregated groups. PMID- 22305205 TI - New therapies in HER2-positive breast cancer: a major step towards a cure of the disease? AB - Overexpression of the human epidermal growth factor receptor 2 (HER2) predicts a poor prognosis in metastatic breast cancer. While the introduction of HER2 targeted therapies, such as the monoclonal antibody trastuzumab and the small molecule tyrosine kinase inhibitor lapatinib, has significantly improved outcomes in HER2+ breast cancer compared with previously available therapies, use of these targeted therapies is often limited by the development of drug resistance and tolerability issues. These limitations create the need for further development and investigation of new targeted therapies that show potent and selective inhibition of these targets or closely connected molecular pathways. Recently, several agents have demonstrated promising activity in HER2+ metastatic breast cancer, either as monotherapy or in combination therapy, including the tyrosine kinase inhibitors neratinib (HKI-272) and afatinib (BIBW-2992) and the anti-HER2 monoclonal antibodies pertuzumab and trastuzumab-DM1 (T-DM1). Agents that target other molecular pathways, such as the vascular endothelial growth factor receptor, mammalian target of rapamycin, PI3-kinases, insulin-like growth factor (IGFR), HSP-90, and other kinases also have potential, in combination with anti HER2 and/or other systemic therapies, to be active in this subtype of breast cancer. Innovative clinical studies are required in well-characterized patient populations to define the true clinical value of these emerging new approaches. PMID- 22305206 TI - Tolerability and efficacy of the intestinal phosphate binder Lantharenol(r) in cats. AB - BACKGROUND: Tolerability and efficacy of the intestinal phosphate binder Lantharenol(r) (lanthanum carbonate octahydrate) were tested in two prospective, randomized and negative controlled laboratory studies with healthy adult cats fed commercial maintenance diets non-restricted in phosphorus. In the first study, the maximal tolerated dose was determined. Starting from a dose of 0.125 g/kg body weight mixed with the daily feed ration, the dose of Lantharenol(r) was doubled every other week until signs of intolerability were observed (N=10 cats compared to 5 untreated controls). In the second study, the effects of feed supplementation for two weeks with approximately 2, 6, and 20% of the maximal tolerated dose on phosphorus excretion patterns and balance were assessed (N=8 cats per group). RESULTS: Lantharenol(r) was found to be safe and well tolerated up to the dose of 1 g/kg bodyweight, corresponding to a concentration of 84 g Lantharenol(r)/kg complete feed, defined as dry matter with a standard moisture content of 12%. Feed supplementation for two weeks with approximately 2-20% of this dosage (i.e., 1.6, 4.8, and 16 g/kg complete feed) resulted in a shift from urinary to faecal phosphorus excretion. Apparent phosphorus digestibility was dose-dependently reduced compared to the control group fed with diet only (N=8). CONCLUSIONS: The feed additive was well accepted and tolerated by all cats. Therefore, Lantharenol(r) presents a well tolerated and efficacious option to individually tailor restriction of dietary phosphorus as indicated, for instance, in feline chronic kidney disease. PMID- 22305207 TI - Dietary long chain n-3 fatty acids are more closely associated with protein than energy intakes from fat. AB - The n-3 fatty acids, eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) regulate hepatic lipid and glucose metabolism; however, EPA and DHA are naturally present in human diets in foods of animal origin, which are generally high in protein with variable triglycerides and uniformly low amounts of carbohydrate. We used dietary information for 611 individuals of 1.5-66 years to address whether EPA and DHA are associated with protein, but not fat intake. EPA, DHA and arachidonic acid (20:4n-6) intakes were positively associated with protein, but not fat intake, whereas linoleic acid (18:2n-6) and alpha-linolenic acid (18:3n-3) intakes were positively associated with fat, but not protein intake. Children 1-3 years of age have lower EPA and DHA intakes than children over 4 years or adults. Recommendations regarding EPA and DHA intake should focus on protein sources, rather than diet fat, and consider their potential roles in amino acid and protein metabolism. PMID- 22305208 TI - Secretion of luteinizing hormone into pituitary venous effluent of the follicular and luteal phase mare: novel acceleration of episodic release during constant infusion of gonadotropin-releasing hormone. AB - We tested the hypothesis that continuous infusion of native GnRH into mares during the estrous cycle, at a dose of 100 MUg/h, would elevate circulating concentrations of LH without disrupting the endogenous, episodic pattern of LH release. Ten cyclic mares were assigned to one of two groups (n = 5/group): (1) Control (saline) and (2) GnRH in saline (100 MUg/h). On experimental day 0 (3 to 6 d after ovulation), osmotic pumps containing saline or GnRH were placed subcutaneously and connected to a jugular infusion catheter. Blood samples were collected from jugular catheters daily and at 5-min intervals from catheters placed in the intercavernous sinus (ICS) for 8 h on experimental day 4 (luteal phase; 7 to 10 d after ovulation), followed by an additional 6-h intensive sampling period 36 h after PGF(2alpha)-induced luteal regression (experimental day 6; follicular phase). Treatment with GnRH increased (P < 0.001) concentrations of LH by 3- to 4-fold in the peripheral circulation and 4- to 5 fold in the ICS. Continuous GnRH treatment accelerated (P < 0.01) the frequency of LH release and decreased the interepisodic interval during both luteal and follicular phases. Treatment with GnRH during the luteal phase eliminated the low frequency, long-duration pattern of episodic LH release and converted it to a high-frequency, short-duration pattern reminiscent of the follicular phase. These observations appear to be unique to the horse. Further studies that exploit this experimental model are likely to reveal novel mechanisms regulating the control of gonadotrope function in this species. PMID- 22305209 TI - Useful lessons from China? PMID- 22305210 TI - New estimates of malaria deaths: concern and opportunity. PMID- 22305211 TI - Keeping patients safe. PMID- 22305212 TI - Genomic medicine and the NHS: it is possible. PMID- 22305213 TI - Born to be wild? PMID- 22305215 TI - Joseph Lau: mastering the meta-analysis. PMID- 22305216 TI - Treatment of Helicobacter pylori in Latin America. PMID- 22305217 TI - Treatment of Helicobacter pylori in Latin America. PMID- 22305218 TI - Treatment of Helicobacter pylori in Latin America. PMID- 22305220 TI - A tale of devolution, abolition, and performance. PMID- 22305221 TI - Improving health: can Pakistan prioritise? PMID- 22305222 TI - Non-communicable diseases and the food and beverage industry. PMID- 22305223 TI - A tale of devolution, abolition, and performance. PMID- 22305224 TI - The Integrated Academic Training programme at Oxford. PMID- 22305225 TI - Global malaria mortality between 1980 and 2010: a systematic analysis. AB - BACKGROUND: During the past decade, renewed global and national efforts to combat malaria have led to ambitious goals. We aimed to provide an accurate assessment of the levels and time trends in malaria mortality to aid assessment of progress towards these goals and the focusing of future efforts. METHODS: We systematically collected all available data for malaria mortality for the period 1980-2010, correcting for misclassification bias. We developed a range of predictive models, including ensemble models, to estimate malaria mortality with uncertainty by age, sex, country, and year. We used key predictors of malaria mortality such as Plasmodium falciparum parasite prevalence, first-line antimalarial drug resistance, and vector control. We used out-of-sample predictive validity to select the final model. FINDINGS: Global malaria deaths increased from 995,000 (95% uncertainty interval 711,000-1,412,000) in 1980 to a peak of 1,817,000 (1,430,000-2,366,000) in 2004, decreasing to 1,238,000 (929,000 1,685,000) in 2010. In Africa, malaria deaths increased from 493,000 (290,000 747,000) in 1980 to 1,613,000 (1,243,000-2,145,000) in 2004, decreasing by about 30% to 1,133,000 (848,000-1,591,000) in 2010. Outside of Africa, malaria deaths have steadily decreased from 502,000 (322,000-833,000) in 1980 to 104,000 (45,000 191,000) in 2010. We estimated more deaths in individuals aged 5 years or older than has been estimated in previous studies: 435,000 (307,000-658,000) deaths in Africa and 89,000 (33,000-177,000) deaths outside of Africa in 2010. INTERPRETATION: Our findings show that the malaria mortality burden is larger than previously estimated, especially in adults. There has been a rapid decrease in malaria mortality in Africa because of the scaling up of control activities supported by international donors. Donor support, however, needs to be increased if malaria elimination and eradication and broader health and development goals are to be met. FUNDING: The Bill & Melinda Gates Foundation. PMID- 22305226 TI - Hereditary angio-oedema. AB - Hereditary angio-oedema is caused by a heterozygous deficiency of C1 inhibitor. This inhibitor regulates several inflammatory pathways, and patients with hereditary angio-oedema have intermittent cutaneous or mucosal swellings because of a failure to control local production of bradykinin. Swellings typically evolve in several hours and persist for a few days. In addition to orofacial angio-oedema, painless swellings affect peripheries, which causes disfigurement or interference with work and other activities of daily living. Angio-oedema affecting the gastrointestinal tract or abdominal viscera causes severe pain often with vomiting due to oedematous bowel obstruction. About 2% of swellings involve the larynx and can be fatal if untreated. About 50% of patients have laryngeal swellings that are potentially fatal despite prophylaxis. In this Seminar we review the clinical features, diagnosis, and management of hereditary angio-oedema, with specific emphasis on the new treatments available for acute swellings. PMID- 22305227 TI - A lethal injection? PMID- 22305228 TI - The growing threat to medical independence in conflict zones. PMID- 22305229 TI - Editorial code of conduct. PMID- 22305230 TI - Editorial code of conduct. PMID- 22305231 TI - McCoy's syndrome: a new medical entity. PMID- 22305232 TI - Possible pet-associated baylisascariasis in child, Canada. PMID- 22305233 TI - Role of phytohormones in insect-specific plant reactions. AB - The capacity to perceive and respond is integral to biological immune systems, but to what extent can plants specifically recognize and respond to insects? Recent findings suggest that plants possess surveillance systems that are able to detect general patterns of cellular damage as well as highly specific herbivore associated cues. The jasmonate (JA) pathway has emerged as the major signaling cassette that integrates information perceived at the plant-insect interface into broad-spectrum defense responses. Specificity can be achieved via JA-independent processes and spatio-temporal changes of JA-modulating hormones, including ethylene (ET), salicylic acid (SA), abscisic acid (ABA), auxin, cytokinins (CK), brassinosteroids (BR) and gibberellins (GB). The identification of receptors and ligands and an integrative view of hormone-mediated response systems are crucial to understand specificity in plant immunity to herbivores. PMID- 22305234 TI - Drug-abusing offenders with comorbid mental disorders: problem severity, treatment participation, and recidivism. AB - This study examined problem severity, treatment participation, and recidivism among 1,016 offenders with co-occurring mental disorders who participated in California's Proposition 36. Participants were assessed using the Addiction Severity Index (ASI) at baseline, and their records on mental health diagnoses, drug treatment participation, and arrests were also obtained. Participants' co occurring disorder (COD) severity was classified as mild or severe based on specific mental health diagnoses. Predictors of recidivism were examined among mild-COD and severe-COD participants separately using ordinal logistic regression. Results indicate that although previous arrests, education, and treatment retention length are predictors of recidivism generally, gender, age, primary drug, ASI drug severity score, and treatment modality are differentially important depending on COD status. These results underscore the need for COD focused intervention strategies among offenders, taking into consideration the severity of their COD status. PMID- 22305235 TI - Fathers entering substance abuse treatment: An examination of substance abuse, trauma symptoms and parenting behaviors. AB - OBJECTIVE: The relationship between fatherhood and both psychiatric distress and severity of substance abuse (SA) among men entering SA treatment has not been well explored. This study was designed to (a) examine differences in symptoms of men presenting for SA assessment based on fatherhood status and (b) determine how posttraumatic stress disorder (PTSD) symptoms and severity of SA were associated with parenting for men who were fathers. METHODS: PTSD symptoms, severity of SA, and parenting data reported on structured questionnaires were collected from 126 men presenting for an SA evaluation at a forensic drug diversion clinic. RESULTS: There were no differences in severity of alcohol or drug use between fathers and nonfathers; however, fathers with more PTSD symptoms reported greater severity of alcohol and drug use. Among the fathers, PTSD symptoms correlated significantly and positively with negative parenting behaviors, whereas SA did not. Fathers with more significant PTSD symptoms were more likely to want help with parenting. CONCLUSIONS: Further exploration of the impact of trauma-related symptoms on the parenting behaviors of substance-abusing men is warranted. PMID- 22305236 TI - Ovarian perivascular epithelioid cell tumor not otherwise specified with transcription factor E3 gene rearrangement: a case report and review of the literature. AB - We report the first case of isolated ovarian perivascular epithelioid cell tumor not otherwise specified in a 33-year-old woman with no history of tuberous sclerosis. A right ovary specimen revealed a well-circumscribed 2.5 * 2 cm solid mass. Microscopically, the mass was composed of nests of tumor cells that were separated by fibrous septa. The tumor cells were composed of pure epithelioid cells with abundant clear cytoplasm and dark brown pigments. Immunohistochemically, the tumor cells showed diffuse and strong cytoplasmic staining of HMB45; however, the tumor cells were not reactive for smooth muscle actin, desmin, inhibin-alpha, calretinin, and carcinoembryonic antigen. Strong nuclear expression of transcription factor E3 protein was observed in most tumor cells, and transcription factor E3 fluorescence in situ hybridization showed transcription factor E3 rearrangements associated with balanced Xp11 translocations. PMID- 22305237 TI - Diffuse reticuloendothelial system involvement in type IV glycogen storage disease with a novel GBE1 mutation: a case report and review. AB - Glycogen storage disease type IV is a rare autosomal recessive disorder of glycogen metabolism caused by mutations in the GBE1 gene that encodes the 1,4 alpha-glucan-branching enzyme 1. Its clinical presentation is variable, with the most common form presenting in early childhood with primary hepatic involvement. Histologic manifestations in glycogen storage disease type IV typically consist of intracytoplasmic non-membrane-bound inclusions containing abnormally branched glycogen (polyglucosan bodies) within hepatocytes and myocytes. We report a female infant with classic hepatic form of glycogen storage disease type IV who demonstrated diffuse reticuloendothelial system involvement with the spleen, bone marrow, and lymph nodes infiltrated by foamy histiocytes with intracytoplasmic polyglucosan deposits. Sequence analysis of the GBE1 gene revealed compound heterozygosity for a previously described frameshift mutation (c.1239delT) and a novel missense mutation (c.1279G>A) that is predicted to alter a conserved glycine residue. GBE enzyme analysis revealed no detectable activity. A review of the literature for glycogen storage disease type IV patients with characterized molecular defects and deficient enzyme activity reveals most GBE1 mutations to be missense mutations clustering in the catalytic enzyme domain. Individuals with the classic hepatic form of glycogen storage disease type IV tend to be compound heterozygotes for null and missense mutations. Although the extensive reticuloendothelial system involvement that was observed in our patient is not typical of glycogen storage disease type IV, it may be associated with severe enzymatic deficiency and a poor outcome. PMID- 22305239 TI - Use of 18S ribosomal DNA polymerase chain reaction-denaturing gradient gel electrophoresis to study composition of fungal community in 2 patients with intestinal transplants. AB - Fungi form a diverse microbial community in the human intestine. Little is known about the succession of species after intestinal transplantation. We investigated the alterations of the gut fungal population in 2 patients with intestinal allografts. The ileal effluent and feces were fingerprinted using denaturing gradient gel electrophoresis, with confirmation by DNA sequencing. Analysis of 18S ribosomal DNA indicated that the phylogenetic diversity of the fungal communities was higher soon after transplantation; less diversity was observed at the later time points in patient 1. The shifts in the denaturing gradient gel electrophoresis banding patterns over time were similar in the effluent and feces in this patient. Similar changes in the fungi in the effluent and feces also were observed in patient 2. Sequence analysis of denaturing gradient gel electrophoresis bands showed that Saccharomyces cerevisiae and Kluyveromyces waltii dominated the fungal microbiota in both patients. Some species, including Candida spp, Cryptococcus neoformans, Fusarium oxysporum, Aspergillus clavatus, and Trichophyton verrucosum, were present early. We report for the first time the temporal alterations in fungal communities in patients with an intestinal allograft. This information may provide novel insight into the roles of the fungal microbiota in the pathophysiology of the transplanted intestine. PMID- 22305240 TI - Microsatellite instability status does not predict total lymph node or negative lymph node retrieval in stage III colon cancer. AB - The relationship between higher total lymph node resection number in colorectal cancer resection specimens and improved overall survival is well known. Recent studies describe an association between a high rate of microsatellite instability and a high total lymph node count in colorectal cancer. Higher lymph node retrieval may potentially explain the improved survival seen in cancers with microsatellite instability. We investigate whether these associations can be validated in a cohort of American Joint Committee on Cancer stage III colon cancers. Medical records from 200 cases of stage III colon cancer resection specimens were reviewed, and sufficient tissue was available for 168. Expression of DNA mismatch repair proteins was determined by immunohistochemistry, and microsatellite status, by polymerase chain reaction. The mean total lymph node count in cases with microsatellite instability versus microsatellite stable tumors (15.9 versus 16.9; P = .664) and the mean number of negative lymph nodes in each respective category (12.2 versus 13.6; P = .522) were not significantly different. There was no difference between microsatellite stable cases and cases with microsatellite instability when total lymph node counts (P = .953) or negative lymph node counts (P = .381) were analyzed with respect to percentage of cases above and below the medians. This cohort of stage III colon cancers does not support a significant relationship between microsatellite status and a higher retrieval of total or negative lymph nodes. Although microsatellite instability is associated with improved overall survival in our cohort (P = .026), the reason for this does not appear to be related to higher numbers of retrieved lymph nodes. PMID- 22305241 TI - KRAS mutations in ovarian low-grade endometrioid adenocarcinoma: association with concurrent endometriosis. AB - The association between ovarian endometrioid adenocarcinoma and endometriosis is well established. However, not all endometrioid adenocarcinomas are directly related to endometriosis, and it has been suggested that there may be clinicopathologic differences between endometriosis-positive and endometriosis negative tumors. Molecular alterations in endometrioid adenocarcinoma include KRAS and BRAF mutations, but the incidence of these abnormalities in previous reports has been highly variable (0%-36% and 0%-24%, respectively). This may be explained by relatively small sample sizes in earlier studies but could also reflect difficulties in accurately classifying high-grade ovarian malignancies. In the current study, we investigated KRAS and BRAF mutations in 78 low-grade (FIGO grade 1 and 2) endometrioid adenocarcinomas and compared the results with the presence of endometriosis in the tumor-associated ovary and/or in other pelvic sites. KRAS mutations were identified in 12 (29%) of 42 endometriosis associated endometrioid adenocarcinomas with satisfactory analysis but in only 1 (3%) of 29 tumors in which endometriosis was not identified. BRAF mutation was identified only in a single endometriosis-associated case. These findings support the hypothesis that endometriosis-associated and independent endometrioid adenocarcinoma may develop via different molecular pathways and that KRAS mutations have an important role only in the former tumors. In contrast, BRAF mutations do not appear to have a significant role in either endometrioid adenocarcinoma subgroup. This may be relevant to future targeted therapies in patients with high-stage or recurrent disease and indicate that histopathologists should carefully examine endometrioid adenocarcinoma specimens, including nonneoplastic tissues, for the presence of endometriosis. PMID- 22305242 TI - Randomised controlled trial with medical leeches for osteoarthritis of the knee. AB - OBJECTIVES: To evaluate the possible efficacy of medical leeches (Hirudo medicinalis) in the treatment of patients with active osteoarthritis of the knee. DESIGN: Unblinded, randomised controlled trial with outpatients in a crossover design with single interventions of either leeches or transcutaneous electrical nerve stimulation (TENS) as comparator. MAIN OUTCOME MEASURES: Change in Lequesne's combined index for pain and function and change (L.I.) and overall assessment of complaints by visual analog scale (VAS). Cross-over at day 42, with further observation period of 21 days. RESULTS: 52 out of 72 screened patients were randomised (intent to treat) to initial treatment with either eight leeches (group 1: 27 patients) or TENS (group 2: 25 patients). Due to phase effects, confirmatory evaluation had to be restricted to the first period. Between days 0 and 21, we observed highly significant (p<0.001) improvements for means of Lequesne's index from 12.07 to 9.37 and for VAS from 5.89 to 4.16 cm for leeches, but no significant differences for TENS. Effect size as group difference was 2.50 for L.I. (95% confidence interval -3.88 to -1.11), resp. -1.86 cm for VAS (95% confidence interval -2.85 to -0.87 cm). 12 patients (5 group 1, 7 group 2) did not finish the trial, mostly due to non-compliance (6). No serious adverse effects were observed. CONCLUSIONS: Single leech therapy showed significant, relevant and sustaining effects, comparable to other trials with leeches. The method deserves further research, esp. into mechanisms of possible specific effects and optimization of dosing by number of leeches and possible repeats. PMID- 22305243 TI - Measuring possible effect on health-related quality of life by tactile massage or relaxation in patients with type 2 diabetes. AB - OBJECTIVE: The aim was to study the effect of tactile massage versus relaxation exercises on health-related quality of life (HRQoL) in patients with type 2 diabetes, at primary-health-care centres in Stockholm county. DESIGN: The study was carried out as a parallel-arm clinical trial. Patients with type 2 diabetes and HbA1c of 6-8%, aged 35-75, with oral anti-diabetic treatment were included. In all, 26 and 27 attendants in the TM and relaxation group, respectively, entered the study and were included in the intention-to-treat analysis. The attendants were offered one weekly session of TM or the use of relaxation exercises at least once weekly for a total of 10 weeks. MAIN OUTCOME MEASURES: HRQoL was measured using the SF-36 questionnaire at baseline, after 10 weeks of therapy and 3 months after the completion of the study. Owing to multiple comparisons the level of statistical significance was set at p<0.01, and values of p>0.01 and <0.05 were regarded as borderline values. RESULTS: One difference over time between the groups was reaching a borderline value in favour of the relaxation group, i.e. the scale of "Role functioning, physical" (p<0.05). CONCLUSIONS: Based on the findings in this study, we conclude that stress relieving techniques with TM or relaxation CD have limited, if any, beneficial effects on health-related quality of life in Swedish-born patients with type 2 diabetes. We cannot, however, rule out that specific patient groups with higher levels of perceived stress could show benefits with this kind of treatment. PMID- 22305244 TI - Osteopathic manipulative treatment effectiveness in severe chronic obstructive pulmonary disease: a pilot study. AB - OBJECTIVES: Few and contrastingly data are available about use of osteopathic manipulative treatment (OMT) in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Comparing the effects of the combination of pulmonary rehabilitation and OMT compared with pulmonary rehabilitation (PR) in patients with severely impaired COPD. SETTING: Rehabilitative pulmonary department. INTERVENTIONS: Patients underwent exercise training, OMT, educational support and nutritional and psychological counselling. MAIN OUTCOMES MEASURES: Exercise capacity through 6 min walk test (6MWT--primary outcome) and pulmonary function test (secondary outcomes) were evaluated at the beginning and at the end of the training. Patients were randomly assigned to receive PR+soft manipulation (G1) or OMT+PR (G2) for 5 days/week for 4 weeks. RESULTS: 20 stable COPD patients (5 female--mean age, 63.8+/-5.1 years; FEV1 26.9+/-6.3% of predicted) referred for in-patient pulmonary rehabilitation were evaluated. Respect to the baseline, 6 MWT statistically improved in both group. In particular, G2 group gained 72.5+/ 7.5 m (p=0.01) and G1 group 23.7+/-9.7 m. Between group comparison showed a difference of 48.8 m (95% CI: 17 to 80.6 m, p=0.04). Moreover, in G2 group we showed a decrease in residual volume (RV--from 4.4+/-1.5 l to 3.9+/-1.5 l, p=0.05). Between group comparison showed an important difference (-0.44 l; 95% CI: -0.26 to -0.62 l, p=0.001). Furthermore, only in G2 group we showed an increase in FEV1. CONCLUSIONS: This study suggests that OMT+PR may improve exercise capacity and reduce RV in severely impaired COPD patients with respect to PR alone. PMID- 22305245 TI - A network-based analysis of traditional Chinese medicine cold and hot patterns in rheumatoid arthritis. AB - OBJECTIVE: Rheumatoid arthritis (RA) is a heterogeneous disease, and traditional Chinese medicine (TCM) can be used to classify RA into different patterns such as cold and hot based on its clinical manifestations. The aim of this study was to investigate potential network-based biomarkers for RA with either a cold or a hot pattern. METHOD: Microarray technology was used to reveal gene expression profiles in CD4(+) T cells from 21 RA patients with cold pattern and 12 with hot pattern. A T-test was used to identify significant differences in gene expression among RA patients with either cold or hot pattern. Cytoscape software was used to search the existing literature and databases for protein-protein interaction information for genes of interest that were identified from this analysis. The IPCA algorithm was used to detect highly connected regions for inferring significant complexes or pathways in this protein-protein interaction network. Significant pathways and functions were extracted from these subnetworks by the Biological Network Gene Ontology tool. RESULT: Four genes were expressed at higher levels in RA patients with cold pattern than in patients with hot pattern, and 21 genes had lower levels of expression. Protein-protein interaction network analysis for these genes showed that there were four highly connected regions. The most relevant functions and pathways extracted from these subnetwork regions were involved in small G protein signaling pathways, oxidation-reduction in fatty acid metabolism and T cell proliferation. CONCLUSION: Complicated network based pathways appear to play a role in the different pattern manifestations in patients with RA, and our results suggest that network-based pathways might be the scientific basis for TCM pattern classification. PMID- 22305246 TI - Peripheral pulsed electromagnetic fields may reduce the placebo effect in migraine patients that do not respond to the sham intervention in a randomized, placebo-controlled, double-blind, cross-over clinical trial. AB - OBJECTIVE: The purpose of the study was to evaluate the effect of the pulsed electromagnetic fields (PEMF) and its possible modulation of the placebo effect in migraine. DESIGN: Placebo-controlled, randomized, double-blind, cross-over clinical trial. SETTING: Government third level hospital. INTERVENTIONS: Patients with migraine were included. PEMF were applied to the wrist with a bracelet. MAIN OUTCOME MEASURES: Frequency and intensity of the migraine attacks at baseline and during treatment were recorded. Also, we valuated the possible influence of gender and the presence of aura in the PEMF and placebo responses. RESULTS: Eighteen patients (fifteen women, 30+/-2 years old) were included. Migraine frequency and intensity was reduced with both PEMF and placebo to a similar extent in the whole population. However, in responders to placebo, migraine intensity was reduced to a median of 100% with the placebo and to 60% with the PEMF, while in non-responders there was only a slight effect of both treatments. Our results do not suggest an influence of gender or presence of aura in the outcomes. CONCLUSIONS: Treatment with PEMF may not alter either migraine intensity or frequency compared to baseline, but may reduce the response to placebo in migraine patients. PMID- 22305247 TI - A pilot study to compare the views of traditionally trained and CAM-trained therapists using the clinical exemplar of the management of neck/upper limb pain to assess barriers to effective integration of approaches. AB - BACKGROUND: In the UK, patients frequently choose complementary (CAM) therapies, particularly for chronic painful musculoskeletal conditions. It is widely agreed that better integration of complementary and traditional healthcare is desirable. We piloted the Benefits and Risks of Treatment Questionnaire to compare the views of different healthcare practitioners about traditional and alternative approaches in one clinical scenario in order to assess barriers to effective integration. METHODS: A cross-sectional survey of healthcare practitioners (primary care practitioners, physiotherapists, pharmacists, osteopaths, chiropractors and acupuncturists) in the UK. The views of all healthcare providers were compared using the exemplar of neck, shoulder and upper arm pain to explore the perceived risks and benefits of different types of therapeutic intervention using a mathematical cluster approach. RESULTS: 448/1254 (36%) useable replies were received representing all six professions. A mean of 14.9 years of experience was reported by participants. The cluster analyses revealed distinct clusters of opinion of benefit: primary care physicians, physiotherapists and pharmacists were significantly more likely to rate a cluster including: anti-inflammatory drugs, steroid injections, steroids, physiotherapy, paracetamol and antidepressants as beneficial for neck, shoulder and upper arm pain. In contrast, osteopaths and chiropractors, but not physiotherapists were significantly more likely to rate a cluster including chiropractic, osteopathy and physiotherapy as beneficial. CONCLUSION: The Beliefs about Risks and Benefits of Treatments Questionnaire can be applied using a postal approach and achieves similar response rates to other surveys amongst healthcare practitioners. Despite widespread agreement that increased integration of traditional and alternative approaches is desirable, the results of this study suggest that experienced practitioners show the strongest belief in the benefit of approaches closest to their own training and background and the most wariness of risk to those therapies furthest from their background. PMID- 22305248 TI - Factors influencing the use of complementary and alternative medicine and whether patients inform their primary care physician. AB - OBJECTIVES: Use of complementary and alternative medicines (CAMs) is widespread. Several studies have explored why individuals chose to use CAM but there are fewer data to explain how its use 'dovetails' with conventional medicine. This study aimed to determine the prevalence of CAM use in the adult population in Australia and the proportion that seek advice or tell their primary care physician after CAM use, and also to investigate which demographic characteristics, health behaviours and health status are associated with CAM use and disclosure. DESIGN: A cross sectional survey. METHODS: a random sample of 1261 adults was interviewed as part of 2010 Queensland Social Survey, which contained questions about CAM use, frequency of use, types of CAM used, reasons for use, discussing and reporting CAM use with the doctor and confidence in CAM use. Relationships were explored using bivariate and multiple logistic regression. MAIN OUTCOME MEASURES: use of CAM; sought advice from doctor before CAM use; informed doctor after CAM use. RESULTS: 61.7% of respondents had used self-prescribed CAM or visited a CAM practitioner. Being female and being younger predicted CAM use. Being male and in better health predicted seeking advice from the doctor before and also after CAM use. CONCLUSION: Our results confirm the relatively high use of CAM in Queensland, Australia and found that a significant proportion of people did not seek advice from their primary care physician before using CAM, or disclose its use afterwards. These factors should be taken into account in the doctor-patient consultation. PMID- 22305249 TI - Measuring differential beliefs in complementary therapy research: an exploration of the Complementary and Alternative Medicine Beliefs Inventory (CAMBI). AB - The Complementary and Alternative Medicine Beliefs Inventory (CAMBI) was developed to provide a comprehensive measure of beliefs believed to differentiate complementary therapy (CT) users from nonusers. The initial evaluation of the CAMBI was based on a relatively homogeneous sample of CT users, which raises questions about its applicability in more generalized samples. This study uses data from a community-based sample of older adults (N=200) to evaluate the utility of the CAMBI in more diverse samples. Results indicated substantial variation in responses to items with each of a priori belief domains (i.e., perceived value of natural treatments, preference for participation in treatments, and orientation toward holistic health) and modest inter-correlation among items within each belief domain. Confirmatory factor analysis results indicated the a priori measurement structure provided a poor fit to obtained data. Post hoc analyses indicated that African Americans and those with less education had less consistent responses to items within each belief domain. Revision and additional development of the CAMBI is needed to enable its use in more diverse research samples. PMID- 22305250 TI - Evaluating the impact of cancer on complementary and alternative medicine use, distress and health related QoL among Australian women: a prospective longitudinal investigation. AB - OBJECTIVES: While several cross-sectional studies have examined psychological correlates of complementary and alternative medicine (CAM) use and cancer, few prospective longitudinal investigations have been reported. This study examined whether CAM use moderated distress and quality of life (HRQoL) from pre- to post cancer. DESIGN: A prospective longitudinal national cohort design. SETTING: Participants were 718 mid-aged women from the Australian longitudinal study on women's health who did not have cancer at survey 1, but who subsequently developed cancer. For each participant, three waves of data were extracted: the wave prior to diagnosis ('pre'), at diagnosis ('cancer'), and after cancer ('post'). MAIN OUTCOME MEASURES: CAM use was measured by the question 'in the past 12 months have you consulted an alternative health practitioner'. Distress was measured by perceived stress (PSS) and depression (CES-D 10), HRQoL was measured by physical and mental health functioning (SF-36). RESULTS: CAM use significantly moderated the change over time in stress [F(561)=3.09, p=0.04], depression [F(494)=3.14, p=0.04], but not HRQoL. CAM-users were significantly more stressed than non-users pre-cancer (p<0.05), but there were no significant differences at subsequent surveys. CAM-users were significantly less depressed post-cancer compared to non-users (p<0.05). CONCLUSIONS: Findings indicated that CAM users may be more psychologically vulnerable than non-users with respect to stress, with CAM acting as an effective psychological, but not HRQoL, intervention. PMID- 22305251 TI - Profile of minority and under-served patients using acupuncture. AB - BACKGROUND: Acupuncture use remains common in the United States, yet little is known of its utilization by minority and underserved populations. Herein we report first visit data capturing patient profiles, types of conditions presented, and self-reports of their experience and satisfaction with acupuncture accessed at a free care clinic with in a large urban safety net hospital. METHODS: Sixty-one adult, English-speaking acupuncture patients were given a 20 min survey after their first visit to a free care acupuncture clinic. RESULTS: Patients were from 12 different countries. Fifty-six percent of the participants were minorities. Sixty-five percent of respondents were female. Average age was 42.1. Eighty percent were acupuncture naive. Patients' health complaints were similar to those of other surveyed mainstream patients with 57% reporting musculoskeletal conditions. Ninety-three percent would recommend a friend or family for acupuncture, 97% rating their overall experience with the acupuncture clinic as either very good or good. CONCLUSIONS: When made available to a diverse population of patients, acupuncture is utilized and perceived to be helpful. In this survey, patients sought treatment for musculoskeletal conditions and were satisfied with their first visit. Future research is warranted. PMID- 22305252 TI - Complementary medicine and safety: a systematic investigation of design and reporting of systematic reviews. AB - OBJECTIVES: The objective of this study was to examine the methods used in systematic reviews of safety across a range of complementary therapies to assess the variation in approach and the potential for developing guidance on conduct and reporting. DESIGN: Systematic reviews focusing on safety were retrieved from NHS Evidence and searches of major databases. A pre-prepared template was used for data extraction. Information extracted included details of search strategies, sources, participants, interventions, reported adverse event/effect(s) and causality assessment. Data extraction was carried out by one researcher and a check for accuracy by a second researcher. Methods were assessed against criteria based on guidance provided by the Cochrane Adverse Effects Methods Group. RESULTS: A total of 2563 citations were screened and 88 systematic reviews were selected for inclusion. The majority focused on the safety of herbs and nutritional supplements. Approximately half the reviews covered all aspects of safety; other reviews addressed specific adverse effects or interactions. Types of data included in the reviews did not always reflect the focus of the review. Search strategies, sources used, quality assessment and assessment of causality also varied. CONCLUSIONS: Detailed examination and comparison of the methods has highlighted several areas in which there is potential for development of guidelines and consensus on standards. These include search strategies, sources of information, data extraction and assessment of causality. The value of systematic reviews in relation to large outcome studies requires further consideration. PMID- 22305253 TI - Placebo effect was influenced by publication year in three-armed acupuncture trials. AB - OBJECTIVES: We investigated the relationship between the placebo effect and the trial or patient characteristics. DATA SOURCES: We identified randomized clinical trials with acupuncture, sham and no-treatment groups in which no-treatment or conventional therapy was applied to the no-treatment group. Thirty-one trials in which no treatment was applied in the no-treatment group were categorised as 'strict' trials. Thirty-nine trials in which no-treatment or conventional therapy was applied to the no-treatment group were categorised as 'less strict' trials. We calculated the treatment effect, defined as the difference in the effect size between the acupuncture and no-treatment groups, and the placebo effect, defined as the difference in the effect size between the sham and no-treatment groups. Then, a random effect meta-regression analysis was performed on the two effects with respect to trial or patient characteristics. RESULTS: The treatment effect was not found to be associated with any factors in both the strict and less strict trials. However, the placebo effect was found to be associated with the publication year in both the strict and less strict trials (P=0.009 and 0.005, respectively). The placebo effect increased by 0.05 in effect size per year in trials that were published more recently. CONCLUSION: While the treatment effect was not influenced by any trial or patient characteristics, the placebo effect was associated with the publication year. PMID- 22305254 TI - Future perspectives of personalized medicine in traditional Chinese medicine: a systems biology approach. AB - Deconstruction of molecular pathways and advances in enabling technology platforms have opened new horizons for disease management, exploring therapeutic solutions to each individual patient beyond the one-size fits all practice. Application of personalized medicine paradigms aims to achieve the right diagnosis and right treatment for the right patient at the right time at the right cost. With the potential to transform medical practice across global communities, personalized medicine is emerging as the flagship of modern medicine. In recent years, the health care paradigm has shifted from a focus on diseases to a major hot of personalized traditional Chinese medicine (TCM) with holistic approach. TCM focuses on health maintenance, emphasizes on enhancing the body's resistance to diseases and especially showes great advantages in early intervention, personalized and combination therapies, etc. Systems biology, a new science of the 21st century, becomes practically available and resembles TCM in many aspects such as study method and design, and is current key component technologies that serves as the major driving force for translation of the personalized medicine revolution of TCM principles into practice, will advance personalized therapy principles into healthcare management tools for individuals and populations. Such system approach concepts are transforming principles of TCM to modern therapeutic approaches, enable a predictive and preventive medicine and will lead to personalized medicine. To realise the full potential of personalized TCM, we describe the current status of principles and practice of TCM integrated with systems biology platform. Some characteristic examples are presented to highlight the application of this platform to personalized TCM research and development as well as some of the necessary milestones for moving TCM into mainstream health care. PMID- 22305255 TI - Quality of herbal medicines: challenges and solutions. AB - The popularity of herbal medicines has risen worldwide. This increase in usage renders safety issues important. Many adverse events of herbal medicines can be attributed to the poor quality of the raw materials or the finished products. Different types of herbal medicines are associated with different problems. Quality issues of herbal medicines can be classified into two categories: external and internal. In this review, external issues including contamination (e.g. toxic metals, pesticides residues and microbes), adulteration and misidentification are detailed. Complexity and non-uniformity of the ingredients in herbal medicines are the internal issues affecting the quality of herbal medicines. Solutions to the raised problems are discussed. The rigorous implementation of Good Agricultural and Collection Practices (GACP) and Good Manufacturing Practices (GMP) would undoubtedly reduce the risk of external issues. Through the use of modern analytical methods and pharmaceutical techniques, previously unsolved internal issues have become solvable. Standard herbal products can be manufactured from the standard herbal extracts. PMID- 22305256 TI - Establishing a web-based integrated surveillance system for early detection of infectious disease epidemic in rural China: a field experimental study. AB - BACKGROUND: A crucial goal of infectious disease surveillance is the early detection of epidemics, which is essential for disease control. In China, the current surveillance system is based on confirmed case reports. In rural China, it is not practical for health units to perform laboratory tests to confirm disease and people are more likely to get 'old' and emerging infectious diseases due to poor living conditions and closer contacts with wild animals and poultry. Syndromic surveillance, which collects non-specific syndromes before diagnosis, has great advantages in promoting the early detection of epidemics and reducing the necessities of disease confirmation. It will be especially effective for surveillance in resource poor settings. METHODS/DESIGN: This is a field experimental study. The experimental tool is an innovative electronic surveillance system, combining syndromic surveillance with the existing case report surveillance in four selected counties in China. In the added syndromic surveillance, three types of data are collected including patients' major symptoms from health clinics, pharmaceutical sales from pharmacies and absenteeism information from primary school. In order to evaluate the early warning capability of the new added syndromic surveillance, the timelines and validity of the alert signals will be analyzed in comparison with the traditional case reporting system. The acceptability, feasibility and economic evaluation of the whole integrated surveillance system will be conducted in a before and after study design. DISCUSSIONS: Although syndromic surveillance system has mostly been established in developed areas, there are opportunities and advantages of developing it in rural China. The project will contribute to knowledge, experience and evidence on the establishment of an integrated surveillance system, which aims to provide early warning of disease epidemics in developing countries. PMID- 22305257 TI - Dissecting the history of anatomy in the Third Reich--1989-2010: A personal account. AB - This paper is a personal narrative of involvement with the revelations of the use of anatomical and pathological specimens of victims of Nazi terror. The narrative documents responses to the question of the retention and use of anatomical and pathological specimens from victims of Nazi terror by leading academic and scientific institutions and organizations in Germany and Austria including the government of the Federal Republic of (West) Germany, the University of Tubingen, the University of Vienna, the Max Planck Society and the Anatomische Gesellschaft. It begins with the public revelations of 1989 and concludes with the September 2010 Symposium on the History of Anatomy during the Third Reich at the University of Wurzburg. The narrative documents a 22-year transition in attitude and responses to the investigation and documentation of the history of anatomy and pathology during the Third Reich. The chronicle includes the 1989 proposed "Call for an International Commemoration" by the author, together with the bioethicist Professor Arthur Caplan, on the occasion of the planned burial of the misbegotten specimens and the responses to that proposal. PMID- 22305258 TI - A parasymphyseal pubic cartilaginous cyst masquerading as a chondrosarcoma. PMID- 22305259 TI - Complaint and litigation in breast imaging - realities, myths and strategies. PMID- 22305260 TI - Advanced glycation end-product Nepsilon-carboxymethyl-Lysine accelerates progression of atherosclerotic calcification in diabetes. AB - OBJECTIVE: Vascular calcification is an active deposition process of calcium phosphate which resembles bone formation and is highly regulated by osteoblast like cells. Existing studies demonstrate that advanced glycation end-products (AGEs) may play a pathogenic role in the vascular calcification process. However, their mechanism remains poorly understood. The aim of our current study is to investigate how non-cross-link and non-fluorescent N(epsilon)-carboxymethyl Lysine (CML), a major immunogen of AGEs, affect the progression of atherosclerotic calcification in diabetes. METHODS: The present study consisted of an in vivo investigation and two in vitro investigations. In study I, male apoE(-/-) mice were first rendered diabetic by the administration of 5 daily intraperitoneal injections of streptozotocin (STZ, 40 mg/kg), and then given a semi-synthetic high-fat diet (HFD) plus daily injections of CML (10mg/kg/day). The mice were euthanized and analyzed at 0 month (group 0M, n = 10), 2 months (group 2M, n = 10), and 4 months (group 4M, n = 10) after the triple administrations of STZ-CML-HFD. In study II, the effects of CML on the apoptosis in macrophages were investigated. RAW264.7 cells were incubated with or without 50 MUg/mL oxLDL plus various concentrations of CML for 48 h. In study III, we investigated whether A7r5 aortic smooth muscle cells were induced into osteoblast like phenotypes by incubation with or without 80 MUg/mL of RAW264.7-derived apoptotic bodies and 50 MUg/mL of oxLDL plus various concentrations of CML (or high-glucose) for 7 days. Related analyses (i.e., H&E staining, Masson staining, von Kossa staining, TUNEL staining, immunohistochemical staining, calcium content assay, annexin V-FITC/PI double-staining, and Western blot) were performed. RESULTS: Morphological analysis showed that early atherosclerotic plaques appeared 2 months after the triple administrations of STZ-CML-HFD, and that typically advanced plaques with extensive calcification lesions, abundant cholesterol crystals, and proliferative collagen were formed 4 months after the triple administrations of STZ-CML-HFD. Furthermore, CML deposition signals and the expression of receptor for advanced glycation end-products (RAGE) in the aortic wall were mainly restricted in the atherosclerotic plaques. After the incubation of A7r5 smooth muscle cells with 10 MUmol/L CML plus 50 MUg/mL oxLDL, and 80 MUg/mL apoptotic bodies (ABs) for 7 days, semi-quantitative analysis of bone morphogenetic protein 2 (BMP-2), core-binding factor alpha1 (cbfalpha1), and alkaline phosphatase (ALP) expression showed 5.0-, 2.0-, and 2.9-fold increases, respectively, compared with those in 50 MUg/mL oxLDL and 80 MUg/mL ABs. Subsequently, a similar trend was observed in the calcium deposition of the cell layer. However, high-glucose had no effects on the ALP activity and calcium deposition of A7r5 cell layer under high-lipid, apoptosis-coexisting conditions. Both animal and cell studies consistently demonstrated that the CML/RAGE axis may first initiate the apoptosis of macrophages in atherosclerotic lesions and then induce BMP-2-cbfalpha1-ALP-calcification cascade in a high-lipid, apoptosis coexisting environment. CONCLUSION: The CML/RAGE axis may play an important role in atherosclerotic calcification of diabetes through the mechanism that induces the apoptosis of macrophages followed by the osteogenic differentiation of aortic smooth muscle cells. PMID- 22305261 TI - Controversies in dyslipidaemia management. PMID- 22305262 TI - Epicardial fat volume and concurrent presence of both myocardial ischemia and obstructive coronary artery disease. AB - OBJECTIVE: Epicardial fat volume (EFV) is linked to cardiovascular event risk. The aim of this study was to evaluate whether EFV is independently related to concurrent presence of both myocardial ischemia and obstructive coronary stenosis. METHODS: We studied 92 consecutive patients without known coronary artery disease (CAD) who underwent Rb-82 PET, coronary calcium scoring (CCS) and invasive coronary angiography (ICA) within 6 months. EFV was computed from non contrast CT by validated software and indexed to body surface-area (EFVi, cm(3)/m(2)). Ischemia was defined by >= 5% difference of total perfusion deficit (quantified by validated software) between stress and rest. Obstructive stenosis was defined >= 50% luminal diameter stenosis. RESULTS: Fifty three patients had both ischemia and stenosis. Compared to those without, patients with both having ischemia and stenosis had significantly higher CCS (1125 +/- 1230 vs. 626 +/- 690, p = 0.02) and EFVi (64.6 +/- 20.6 vs. 49.7 +/- 14.2 cm(3)/m(2), p=0.0002). On multivariable analysis after adjusting age, gender, cardiovascular risk factors, chest pain, and CCS (>= 400), only elevated EFVi (>68.1cm(3)/m(2)) significantly predicted concurrent presence of both ischemia and stenosis (odds ratio 6.18, 95% confidence interval 1.73-22.01, p = 0.005). Area under the receiver-operator-characteristic analysis demonstrated a trend towards improved incremental prediction of concurrent myocardial ischemia and obstructive stenosis over age, gender, chest pain, and high CCS (0.73 vs. 0.65, p = 0.09). CONCLUSIONS: Our study suggests that elevated EFVi measured using non-contrast CT may be related to concurrent presence of both ischemia and stenosis. PMID- 22305263 TI - Duration of type 2 diabetes strongly predicts all-cause and cardiovascular mortality in people referred for coronary angiography. AB - OBJECTIVE: Type 2 diabetes represents a major cardiovascular risk factor. However, few studies have addressed the impact of the disease duration on mortality. Thus, we aimed to investigate the predictive value of diabetes duration for all-cause and cardiovascular mortality in subjects undergoing coronary angiography. METHODS: We studied 2455 participants of the LUdwigshafen RIsk and Cardiovascular health study (1768 males/687 females). They had a mean +/ standard deviation (SD) age of 63.1 +/- 9.0 years (range: 40.0-79.9) and a mean +/- SD body mass index of 27.7 +/- 4.0 kg/m(2). 704 subjects were newly diagnosed with type 2 diabetes according to the 2010 criteria of the American Diabetes Association and 446 subjects had a known history of type 2 diabetes. The mean +/- SD duration of the follow-up for all-cause and cardiovascular mortality was 7.4 +/- 2.3 years. RESULTS: A total of 543 deaths occurred during the follow-up. Among these, 343 were accounted for by cardiovascular diseases. The duration of type 2 diabetes was strongly and positively correlated with all-cause and cardiovascular mortality (both P<0.001). The multivariate adjusted hazard ratios (95% confidence intervals) for cardiovascular mortality compared to subjects without diabetes were 1.76 (1.34-2.32), 2.86 (2.00-4.08), 2.96 (1.85-4.74), and 4.55 (3.24-6.39) for subjects with new onset type 2 diabetes and subjects with known type 2 diabetes (duration <= 5, >5 and <= 10, >10 years), respectively. CONCLUSIONS: The data emphasise the need to consider the diabetes duration for the prediction of mortality in subjects at intermediate to high cardiovascular risk. PMID- 22305264 TI - [Comparative study of the biodistribution of (99m)Tc-HYNIC-Lys3-Bombesin obtained with the EDDA/tricine and NA/tricine as coligands]. AB - The aim of present investigation was to evaluate biodistribution in healthy animals and in tumor models of the radiopharmaceuticals (99m)Tc-EDDA/tricine HYNIC-Lys3-Bombesin (HYNIC-Lys3-BN) and (99m)Tc-NA/tricine-HYNIC-Lys3-BN. Biodistribution and pharmacokinetics were carried out over 24 hours. To do so, 24 healthy Wistar rats were used and were administered 37.0 +/- 0.8 MBq/rat of each radiopharmaceutical. For the tumor model study, 20 CD-1 nude mice were used and prostate tumors (PC3) were implanted in all the mice. Ten days later, tumor volumes were calculated and 40.00 +/- 0.04 MBq/mice of each radiopharmaceutical were injected. Both showed high radiochemical purity: 98.08 +/- 0.25% for EDDA/tricine product and 95.1 +/- 0.3% for the conjugate with NA/tricine. Uptake of the radiopharmaceutical with NA/tricine was significantly higher in organs of the reticulo-endothelial system of healthy Wistar rats during 24h, specifically in the liver and spleen. Both labeled compounds showed no significant differences between their blood elimination half lives. Average of tumor growth was 0.93 +/- 0.02 cm(3) and affinity for tumors showed a growing and specific binding of both radiopharmaceuticals, although it was significantly higher for the EDDA/tricine conjugate. This outcome made it possible to corroborate the direct relationship between the density of gastrin releasing peptide and its receptors (GRPr) and the variation of the accumulation of the radiopharmaceuticals in the tumor. Use of EDDA/tricine as coligand is more appropriate than NA/tricine for labeling of HYNIC-Lys3-BN with (99m)Tc. PMID- 22305265 TI - Determinants of physical activity in daily life in candidates for lung transplantation. AB - BACKGROUND: Participation in daily physical activity (PA) has never been objectively assessed in candidates for lung transplantation (LTx). The main research questions were: 1) How active are LTx-candidates in daily life? 2) What are determinants of activity behavior before LTX? METHODS: Ninety-six candidates for LTx (diagnosis of COPD or interstitial lung disease; mean age 55 +/- 7 years) underwent measurements of PA, pulmonary function, 6-min walking distance (6MWD), muscle force and health-status (SF-36 scale). RESULTS: Patients were markedly inactive (5% of waking hours walking, 26% standing and 69% sedentary). Backward multiple regression identified 6MWD (expressed as % of predicted value; beta = 73.0 steps, partial r(2) = 0.36, p = 0.00), a higher score on the energy/fatigue scale of the SF-36 (beta = 28.6 steps, partial r(2) = 0.09, p = 0.00) and a higher expiratory muscle force (expressed as % of predicted value; beta = 11.8 steps, partial r(2) = 0.05, p = 0.02) as determinants of daily steps. Minutes of mild to moderate (>=2 METs) activity were determined by 6MWD (expressed as % of predicted value; beta = 2.14 min, partial r(2) = 0.30, p = 0.00), inspiratory muscle force (expressed as % of predicted value; beta = 0.33 min, partial r(2) = 0.04, p = 0.05) and seasonal influences (spring/summer vs. autumn/winter: beta = 18.95 min, partial r(2) = 0.04, p = 0.05). The overall fit of the models was r(2) = 0.50 and r(2) = 0.38, respectively. CONCLUSIONS: The 6MWD was the main determinant of an inactive lifestyle in these patients. Respiratory muscle force, energy and fatigue and seasonal variations explained some additional variability in activity behavior. Patients should be encouraged to participate in interventions aimed at improving physical fitness and participation in daily physical activity before LTx. PMID- 22305266 TI - Cytoplasmic p21 induced by p65 prevents doxorubicin-induced cell death in pancreatic carcinoma cell line. AB - BACKGROUND: Studies have shown the existence of p21 induction in a p53-dependent and -independent pathway. Our previous study indicates that DOX-induced p65 is able to bind the p21 promoter to activate its transactivation in the cells. METHODS: Over-expression and knock-down experiments were performed in Human Pancreatic Carcinoma (PANC1) cells. Cell cycle and cell death related proteins were assessed by Western Blotting. Cytotoxicity assay was checked by CCK-8 kit. Cell growth was analyzed by flow cytometers. RESULTS: Here we showed that over expression of p65 decreased the cytotoxic effect of DOX on PANC1 cells, correlating with increased induction of cytoplasmic p21. We observed that pro caspase-3 physically associated with cytoplasmic p21, which may be contribution to prevent p21 translocation into the nucleus. Our data also suggested that no clear elevation of nuclear p21 by p65 provides a survival advantage by progression cell cycle after treatment of DOX. Likewise, down-regulation of p65 expression enhanced the cytotoxic effect of DOX, due to a significant decrease of mRNA levels of anti-apoptotic genes, such as the cellular inhibitor of apoptosis 1 (c-IAP1), and the long isoform of B cell leukemia/lymphoma-2 (Bcl-2), leading to efficient induction of caspase-3 cleavage in the cells. More, we present evidence that over-expression of p53 or p53/p65 in the PANC1 cells were more sensitive to DOX treatment, correlated with activation of caspase-3 and clear elevation of nuclear p21 level. Our previous data suggested that expression of p21 increases Gefitinib-induced cell death by blocking the cell cycle at the G1 and G2 phases. The present findings here reinforced this idea by showing p21's ability of potentiality of DOX-induced cell death correlated with its inhibition of cell cycle progression after over-expression of p53 or p53/p65. CONCLUSION: Our data suggested p65 could increase p53-mediated cell death in response to DOX in PANC1 cells. Thus, it is worth noting that in p53 null or defective tumors, targeting in down-regulation of p65 may well be useful, leading to the potentiality of chemotherapeutic drugs. PMID- 22305267 TI - Bypass of cell cycle arrest induced by transient DNMT1 post-transcriptional silencing triggers aneuploidy in human cells. AB - BACKGROUND: Aneuploidy has been acknowledged as a major source of genomic instability in cancer, and it is often considered the result of chromosome segregation errors including those caused by defects in genes controlling the mitotic spindle assembly, centrosome duplication and cell-cycle checkpoints. Aneuploidy and chromosomal instability has been also correlated with epigenetic alteration, however the molecular basis of this correlation is poorly understood. RESULTS: To address the functional connection existing between epigenetic changes and aneuploidy, we used RNA-interference to silence the DNMT1 gene, encoding for a highly conserved member of the DNA methyl-transferases. DNMT1 depletion slowed down proliferation of near-diploid human tumor cells (HCT116) and triggered G1 arrest in primary human fibroblasts (IMR90), by inducing p53 stabilization and, in turn, p21waf1 transactivation. Remarkably, p53 increase was not caused by DNA damage and was not observed after p14-ARF post-transcriptional silencing. Interestingly, DNMT1 silenced cells with p53 or p14-ARF depleted did not arrest in G1 but, instead, underwent DNA hypomethylation and became aneuploid. CONCLUSION: Our results suggest that DNMT1 depletion triggers a p14ARF/p53 dependent cell cycle arrest to counteract the aneuploidy induced by changes in DNA methylation. PMID- 22305268 TI - Deciphering the role of Paenibacillus strain Q8 in the organic matter recycling in the acid mine drainage of Carnoules. AB - BACKGROUND: The recycling of the organic matter is a crucial function in any environment, especially in oligotrophic environments such as Acid Mine Drainages (AMDs). Polymer-degrading bacteria might play an important role in such ecosystem, at least by releasing by-products useful for the rest of the community. In this study, physiological, molecular and biochemical experiments were performed to decipher the role of a Paenibacillus strain isolated from the sediment of Carnoules AMD. RESULTS: Even though Paenibacillus sp. strain Q8 was isolated from an oligotrophic AMD showing an acidic pH, it developed under both acidic and alkaline conditions and showed a heterotrophic metabolism based on the utilization of a broad range of organic compounds. It resisted to numerous metallic stresses, particularly high arsenite (As(III)) concentrations (> 1,800 mg/L). Q8 was also able to efficiently degrade polymers such as cellulose, xylan and starch. Function-based screening of a Q8 DNA-library allowed the detection of 15 clones with starch-degrading activity and 3 clones with xylan-degrading activity. One clone positive for starch degradation carried a single gene encoding a "protein of unknown function". Amylolytic and xylanolytic activities were measured both in growing cells and with acellular extracts of Q8. The results showed the ability of Q8 to degrade both polymers under a broad pH range and high As(III) and As(V) concentrations. Activity measurements allowed to point out the constitutive expression of the amylase genes and the mainly inducible expression of the xylanase genes. PACE demonstrated the endo-acting activity of the amylases and the exo-acting activity of the xylanases. CONCLUSIONS: AMDs have been studied for years especially with regard to interactions between bacteria and the inorganic compartment hosting them. To date, no study reported the role of microorganisms in the recycling of the organic matter. The present work suggests that the strain Q8 might play an important role in the community by recycling the scarce organic matter (cellulose, hemicellulose, starch...), especially when the conditions change. Furthermore, function-based screening of a Q8 DNA library allowed to assign an amylolytic function to a gene previously unknown. AMDs could be considered as a reservoir of genes with potential biotechnological properties. PMID- 22305269 TI - Zika virus infection, Cambodia, 2010. PMID- 22305270 TI - Invasive pneumococcal pneumonia and respiratory virus co-infections. AB - To confirm whether respiratory virus infections increase susceptibility to invasive pneumococcal pneumonia, we examined data from 11 influenza seasons (1994 2005) in the United States. Invasive pneumococcal pneumonia was significantly associated with influenza and respiratory syncytial virus activities in 5 seasons. Association strength was higher when strain H3N2 was the predominant influenza A virus strain. PMID- 22305272 TI - Elective sac perfusion to reduce the risk of neurologic events following endovascular repair of thoracoabdominal aneurysms. AB - Spinal cord ischemia (SCI) is a catastrophic complication of thoracoabdominal aortic aneurysm (TAAA) repair. This article describes our early experience with a technique for maintaining perfusion of segmental vessels (intercostals and lumbars) in the early postoperative period after endovascular repair of a TAAA, with "sac perfusion branches" added to custom-made stent grafts. These are closed 7 to 10 days after the first procedure to complete exclusion of the aneurysm. We have used this technique in 10 patients with type II TAAAs. One developed monoparesis of the right leg during a period of hypotension secondary to a cardiac event and died within 30 days. Two patients developed lower limb weakness after closure of the perfusion branches, both with full recovery. Controlled perfusion of segmental vessels with perfusion branches is feasible and may be a useful adjunct to prevent SCI, providing protection to spinal cord perfusion during the immediate postoperative period when risk of SCI is greatest. PMID- 22305271 TI - Role of aortic stent graft oversizing and barb characteristics on folding. AB - OBJECTIVE: To evaluate folding in infrarenal stent grafts in relation to oversizing, barb angle, and barb length using computed tomography images of stent grafts deployed in explanted bovine aortas. METHODS: Computed tomography data from an in vitro investigation on the effect of oversizing of 4% to 45% (n = 19), barb length of 2 to 7 mm (n = 11), and barb angle of 10 degrees to 90 degrees (n = 7) on device fixation were examined for instances of folding. Folding was classified as circumferential or longitudinal and quantified on an ordinal scale based on codified criteria. Cumulative fold ranking from 0 (no fold) to 6 (two severe folds) for each deployment was used as the measure of folding observed. RESULTS: Of the 37 cases, cumulative mean +/- standard deviation fold ranking for stent grafts oversized >30% (n = 5) was significantly greater than the rest (3.4 +/- 1.7 vs 0.5 +/- 1.2, respectively; Mann-Whitney U test; P < .005). When barb length was varied from 2 to 7 mm (oversizing held at 10%-20%), folding was noted in one of 11 cases. Similarly, when barb angle was varied from 0 degrees (vertical) to 90 degrees (horizontal), folding was not noted in any of the seven cases. The pullout force was not significantly different between stent grafts with and without folding (5.4 +/- 1.95 vs 5.12 +/- 1.89 N, respectively; P > .5). At least one instance of folding was noted in the seven of seven (100%) stent grafts with oversizing >23.5% and in only five of 30 (14%) stent grafts with oversizing <23.5%. CONCLUSIONS: Stent graft folding was prevalent when oversized >30%. Large variations in barb length and angle did not aggravate folding risk when oversized within the recommended range of 10% to 20%. PMID- 22305273 TI - A prospective randomized open-label crossover trial of regional citrate anticoagulation vs. anticoagulation free liver dialysis by the Molecular Adsorbents Recirculating System. AB - INTRODUCTION: The Molecular Adsorbent Recycling System (MARS) is used to treat patients with liver failure. Observational data suggest that citrate anticoagulation during MARS is feasible. Comparative studies on the optimal anticoagulation regimen during MARS are lacking. The aim of the current study was to evaluate two heparin-free anticoagulation regimens. METHODS: We performed a prospective randomized open-label crossover study of regional citrate anticoagulation against no anticoagulation. Ten patients (age 55+/-11 years) with liver failure undergoing MARS treatment were included. The primary endpoint was completion of MARS sessions. Secondary endpoints included treatment efficacy and safety. Longevity of MARS treatment was plotted as a Kaplan-Meier estimate. Fisher's exact test was used for contingency table analysis. RESULTS: Of a total of 27 6-hour sessions, four sessions had to be terminated prematurely, three due to occlusive clotting of the extracorporeal circuit and one due to uncontrollable bleeding from the vascular access site. All four events occurred in the group without anticoagulation. Between group comparison demonstrated citrate anticoagulation to significantly increase the likelihood of completed MARS treatment (Fisher's exact test, P 0.04). This translates into higher bilirubin reduction ratios when citrate was applied (reduction ratio 0.25 vs. 0.15, P 0.02). Systemic ionized calcium concentrations were significantly reduced during citrate anticoagulation (P<0.001) but remained within a safe range. We observed no major adverse events. CONCLUSIONS: Regional citrate anticoagulation in patients with liver failure is feasible. Citrate anticoagulation provides superior patency of the extracorporeal circuit. Avoidance of anticoagulation during MARS results in significant loss of treatment efficacy, due to treatment downtime. Additional studies are required to identify the optimal anticoagulation regimen for extracorporeal circulation in patients with liver failure. PMID- 22305274 TI - Increasing rates of contralateral prophylactic mastectomy - a trend made in USA? AB - BACKGROUND: Numerous recent studies conducted in the USA reported a considerable rise in the rates of contralateral prophylactic mastectomy (CPM) in early-stage breast cancer (BC). However, this aggressive surgical approach only showed an evidence-based improvement in prognosis for a small subgroup of high-risk BC patients. We present the first European study reporting CPM rates in an unselected cohort of patients with BC. PATIENTS & METHODS: The data of 881 patients (<= 80 years) who underwent surgery for stage I-III BC from 1995 to 2009 at the University of Basel Breast Center was analyzed. RESULTS: CPM was performed in 23 of 881 patients (2.6%). Of the entire patient population, 37.5% underwent ipsilateral mastectomy and of those, only 7.0% chose to undergo CPM. Importantly, there was no trend over time in the rate of CPM. Women who chose CPM were significantly younger (54 vs. 60 years, p < 0.001), had more often a positive family history (39.1% vs. 24.4%, p = 0.032) and tumors of lobular histology (30.5% vs. 13.9%, p = 0.035). CONCLUSIONS: Our analysis of CPM rates in BC patients, conducted at a European University breast center, does not show the considerably rising CPM rates observed in the USA. We hypothesize that different medico-social and cultural factors, which are highlighted by a different public perception of BC and a different attitude toward plastic surgery, determine the varying CPM rates between the USA and Europe. PMID- 22305275 TI - Ropren((r)) is a polyprenol preparation from coniferous plants that ameliorates cognitive deficiency in a rat model of beta-amyloid peptide-(25-35)-induced amnesia. AB - This study assesses the efficacy of a fixed dose of Ropren((r)) (a plant preparation isolated from the neutral fraction of an extract of spruce needles) on cognitive impairment in rats with beta-amyloid peptide-(25-35)-induced amnesia. Ropren((r)) was administered at a dose of 8.6mg/kg for 28 days, per os, to rats with beta-amyloid peptide-(25-35)-induced amnesia. Cognitive performance was assessed using the passive avoidance paradigm and the Morris water maze and behavior was assessed using the open field test. After four weeks, Ropren((r)) treatment significantly improved non-spatial and spatial learning in rats with beta-amyloid peptide-(25-35)-induced amnesia. The results of the present study suggest that Ropren((r)), a novel plant preparation, ameliorates cognitive deficiencies in an animal model relevant to Alzheimer's disease. PMID- 22305276 TI - Use of curcuminoids in a cohort of patients with oral lichen planus, an autoimmune disease. AB - OBJECTIVES: To summarize long-term open-label use of curcuminoids and experience of side-effects in 53 patients with the autoimmune condition oral lichen planus (OLP) who had previously participated in randomized controlled trials (RCTs) of curcuminoids at UCSF. METHODS: This descriptive retrospective cohort study conducted in 2009 collected information from clinic charts and patient interview on the over-the-counter (OTC) use of curcuminoids during a 1-5 year follow-up period. Of the 53 eligible patients, 33 had previously participated in a RCT (2003-2004) that evaluated a dose of 2000mg/day of curcuminoids and which was ended early for futility and 20 had participated in a RCT (2007-2008) that evaluated a dose of 6000mg/day which demonstrated its efficacy. At the last study visit of each of the 2 RCTs all participants were given current published information about curcuminoids, and some went on to take OTC curcuminoids. RESULTS: Follow-up data was available on 43 participants [25/33 (75%) from the first and 19/20 (95%) from the second RCT]. 18/25 (72%) participants from the first trial took OTC curcuminoids after completion of the trial period. The mean total daily dose was 2137.5mg (SD=793, range 500-3000mg) and mean duration of curcuminoids use was 30 months (SD=27.5). The total follow-up time after completion of the RCT for the 18 participants was mean 68.2 months (SD 5.9). 10/18 (56%) reported that curcuminoids controlled OLP symptoms, and the mean duration of use among these patients was 35.8 months (SD 27.4). 8/18 (44%) were unsure whether curcuminoids helped and the mean duration of use was 21.0 months (SD 27.3). 2 of 18 patients (11%) reported a side-effect (SE) of diarrhea. 19/19 (100%) patients from the second trial took OTC curcuminoids after completion of the trial period. The mean total daily dose was 5058mg (SD=1445, range 1000 6000mg) and mean duration of curcuminoids use 9.6 months (SD=8.04). The total follow-up time after completion of the RCT for the 19 participants was mean 15.8 months (SD 4.8). 12/19 (63%) reported that curcuminoids controlled OLP symptoms, and the mean duration of use was 14.1 months (SD 6.7). 2/19 (11%) reported lack of improvement with a daily dose of 1500mg and 2500mg for 3 months each. 5/19 (26%) were unsure whether curcuminoids helped and the mean duration of use was 1.5 months (1.2 SD). Six of these 19 patients (32%) reported SEs, three had abdominal discomfort, two diarrhea and one slight urgency in defecation on the capsule but not the tablet formulation. The SEs resolved with dose reduction to 4500mg/day in one and 3000mg/day in two patients, while two patients [2/19 (11%)] discontinued curcuminoids due to the SE. CONCLUSIONS: A total of 22/37 (60%) of patients reported a reduction of symptoms with curcuminoids, 13/37 (35%) were unsure and 2/37 (5%) reported that it did not help in reduction of symptoms. Side effects included abdominal discomfort and diarrhea, however occurrence was dose related, and complaints were mild. PMID- 22305277 TI - Ethanolic extracts of Brazilian red propolis increase ABCA1 expression and promote cholesterol efflux from THP-1 macrophages. AB - The ATP-binding cassette transporter A1 (ABCA1) is a membrane transporter that directly contributes to high-density lipoprotein (HDL) biogenesis by regulating the cellular efflux of cholesterol. Since ABCA1 plays a pivotal role in cholesterol homeostasis and HDL metabolism, identification of a novel substance that is capable of increasing its expression would be beneficial for the prevention and therapy of atherosclerosis. In the present study, we studied the effects of ethanolic extracts of Brazilian red propolis (EERP) on ABCA1 expression and cholesterol efflux in THP-1 macrophages. EERP enhanced PPARgamma and liver X receptor (LXR) transcriptional activity at 5-15MUg/ml, which was associated with upregulation of PPARgamma and LXRalpha expression. It was also found that EERP increase the activity of the ABCA1 promoter, which is positively regulated by LXR. Consistent with these findings, treatment with EERP increased both mRNA and protein expression of ABCA1. Finally, EERP upregulated ApoA-I mediated cholesterol efflux. Our results showed that EERP promote ApoA-I-mediated cholesterol efflux from macrophages by increasing ABCA1 expression via induction of PPARgamma/LXR. PMID- 22305278 TI - Fucoxanthin promotes translocation and induction of glucose transporter 4 in skeletal muscles of diabetic/obese KK-A(y) mice. AB - Fucoxanthin (Fx) isolated from Undaria pinnatifida suppresses the development of hyperglycemia and hyperinsulinemia of diabetic/obese KK-A(y) mice after 2 weeks of feeding 0.2% Fx-containing diet. In the soleus muscle of KK-A(y) mice that were fed Fx, glucose transporter 4 (GLUT4) translocation to plasma membranes from cytosol was promoted. On the other hand, Fx increased GLUT4 expression levels in the extensor digitorum longus (EDL) muscle, although GLUT4 translocation tended to increase. The expression levels of insulin receptor (IR) mRNA and phosphorylation of Akt, which are in upstream of the insulin signaling pathway regulating GLUT4 translocation, were also enhanced in the soleus and EDL muscles of the mice fed Fx. Furthermore, Fx induced peroxisome proliferator activated receptor gamma coactivator-1alpha (PGC-1alpha), which has been reported to increase GLUT4 expression, in both soleus and EDL muscles. These results suggest that in diabetic/obese KK-A(y) mice, Fx improves hyperglycemia by activating the insulin signaling pathway, including GLUT4 translocation, and inducing GLUT4 expression in the soleus and EDL muscles, respectively, of diabetic/obese KK-A(y) mice. PMID- 22305279 TI - Eradication of Propionibacterium acnes biofilms by plant extracts and putative identification of icariin, resveratrol and salidroside as active compounds. AB - Propionibacterium acnes is a Gram-positive bacterium that plays an important role in the pathogenesis of acne vulgaris. This organism is capable of biofilm formation and the decreased antimicrobial susceptibility of biofilm-associated cells may hamper efficient treatment. In addition, the prolonged use of systemic antibiotic therapy is likely to lead to the development and spread of antimicrobial resistance. In the present study we investigated whether P. acnes biofilms could be eradicated by plant extracts or their active compounds, and whether other mechanisms besides killing of biofilm cells could be involved. Out of 119 plant extracts investigated, we identified five with potent antibiofilm activity against P. acnes (extracts from Epimedium brevicornum, Malus pumila, Polygonum cuspidatum, Rhodiola crenulata and Dolichos lablab). We subsequently identified icariin, resveratrol and salidroside as active compounds in three of these extracts. Extracts from E. brevicornum and P. cuspidatum, as well as their active compounds (icariin and resveratrol, respectively) showed marked antibiofilm activity when used in subinhibitory concentrations, indicating that killing of microbial cells is not their only mode of action. PMID- 22305280 TI - [Adherence: definitions and measurement methods: characteristics of adherence to topical treatments]. AB - Taking into account topical treatment compliance is extremely important given its fundamental place in the dermatologist's armamentarium. After reviewing the definition of compliance, adherence, alliance, and clinical inertia, the direct methods used to measure compliance with a topical treatment (counting tubes administered, MEMS system performance, measuring circulating blood or urine rate of a medication or its metabolite, and observation of medication intake by a third party) and indirect methods (questioning the patient, the dermatologist's opinion) will be reviewed. The question of frequency, more important than compliance in cases of topical treatments compared to systemic treatments, has given rise to controversial opinions. Six factors related to topical treatment that play a role in therapeutic compliance can be cited: the perception of efficacy, the feeling of harmlessness, the treatment's simplicity, the treatment's duration, the galenic formulation, and the cost. PMID- 22305281 TI - [Adherence of local (and general) treatments in psoriasis]. AB - Several studies dealing with adherence of treatments for psoriasis have been published, using various methods, including questionnaires for self-reporting, interviews, counting/ weighting of unused medication and electronic measuring systems that record every cap unscrewing. Adherence to treatments is limited first by prescriptions not redeemed and then by under dosing in up to 95% of patients. The mean measured compliance is close to 50/60% and is lower than the self reported compliance in all studies. Adherence to topical treatment of psoriasis is limited by difficult self-application, greasy vehicle, number of applications, side effects or fear of side effects. Adherence decreases with time, although an increase in frequency of application is recorded before control visits. A better compliance increases the therapeutic effect. The motivation of dermatologists, the type and quality of the prescribed medicine and clear explanations are simple factors that contribute to increase adherence. PMID- 22305282 TI - [The role of dermatologist in adherence to treatment]. AB - Adherence to treatment is often partial in the course of chronic cutaneous disease but can be improved by the dermatologist. Patient participation in the therapeutic decision is indispensable. Dialogue between patient and dermatologist should provide an understanding of the patient's expectations of the treatment, his or her preferences, and which treatment can be integrated into the patient's lifestyle, and should also provide the patient with an understanding of what the treatment can provide and what its disadvantages may be. The approach to poor compliance differs depending on whether or not it is intentional, with all points between obviously possible. Repeated consultations can maintain and enhance the relation between physician and patient, each visit stimulating adherence to the treatment.The language used by the dermatologist should be clear and simple, adapted to each patient. The simplest, most effective, and best tolerated treatments are followed best. PMID- 22305283 TI - [Non adherent patients in dermatology]. AB - Non compliance to therapy is frequent in dermatological disorders. Many factors related to the disease, treatment, the physician-patient relationship, the physician, and the patient explain this poor compliance during the course of dermatological treatments. Better knowledge of the non compliant patient-related factors could improve treatment compliance, resulting in better treatment efficacy. The patient parameters playing a part in therapy compliance are numerous and closely intertwined: age, sex, marital status, employment, education level, acceptance of the disease, perception of the treatment, associated psychiatric disorders, addictive behaviors, quality of life, the environment, and the relationship with the physician. It is important to take into account these noncompliance factors related to patient typology so as to optimize management of dermatological disorders. This requires knowing the patient's situation and habits well so that the treatment can be adapted as best possible to his or her lifestyle. PMID- 22305284 TI - [Reflections about non compliance]. AB - Throughout the follow up of a patient suffering from a chronic cutaneous disease, non compliance is rarely avoidable. It is provoked by numerous factors, which have to be looked for in the patient and the doctor, as well, and in the external reality, as in the internal, psychic, reality, both of the patient and the doctor. Being aware of these factors is fundamental for resolving the non compliance conflict. Thus, non compliance can become a chance to seize for avoiding patients' wandering and building a more dynamic, authentic and stronger doctor-patient relationship. PMID- 22305285 TI - [Non adherence and topical steroids]. AB - Compliance raises very specific questions in dermatology related to the frequent use of local treatments: creams or ointments, including topical corticosteroids. The adherence in dermatology is a complex issue. It is difficult to quantify objectively because of the patient subjectivity, the constant adaptation to changes in the course of the disease, and due to the lack of adapted device. Moreover poor compliance may be related to topical corticosteroid phobia, defined as a fear vis-a-vis the topical corticosteroids, rational or not. The topical corticosteroid phobia is very common in the management of chronic inflammatory skin diseases especially in atopic dermatitis. PMID- 22305286 TI - Phasic mesolimbic dopamine signaling precedes and predicts performance of a self initiated action sequence task. AB - BACKGROUND: Sequential reward-seeking actions are readily learned despite the temporal gap between the earliest (distal) action in the sequence and the reward delivery. Fast dopamine signaling is hypothesized to mediate this form of learning by reporting errors in reward prediction. However, such a role for dopamine release in voluntarily initiated action sequences remains to be demonstrated. METHODS: Using fast-scan cyclic voltammetry, we monitored phasic mesolimbic dopamine release, in real time, as rats performed a self-initiated sequence of lever presses to earn sucrose rewards. Before testing, rats received either 0 (n = 11), 5 (n = 11), or 10 (n = 8) days of action sequence training. RESULTS: For rats acquiring the action sequence task at test, dopamine release was strongly elicited by response-contingent (but unexpected) rewards. With learning, a significant elevation in dopamine release preceded performance of the proximal action and subsequently came to precede the distal action. This predistal dopamine release response was also observed in rats previously trained on the action sequence task, and the amplitude of this signal predicted the latency with which rats completed the action sequence. Importantly, the dopamine response to contingent reward delivery was not observed in rats given extensive pretraining. Pharmacological analysis confirmed that task performance was dopamine-dependent. CONCLUSIONS: These data suggest that phasic mesolimbic dopamine release mediates the influence that rewards exert over the performance of self-paced, sequentially-organized behavior and sheds light on how dopamine signaling abnormalities may contribute to disorders of behavioral control. PMID- 22305287 TI - Hair cortisol level as a biomarker for altered hypothalamic-pituitary-adrenal activity in female adolescents with posttraumatic stress disorder after the 2008 Wenchuan earthquake. AB - BACKGROUND: The present study evaluated the accumulated changes in hair cortisol levels of patients with posttraumatic stress disorder (PTSD) attributed to the 2008 Wenchuan earthquake in China. METHODS: Sixty-four female adolescents from two townships who experienced the earthquake were recruited 7 months after the disaster, including 32 subjects with PTSD (PTSD group) and 32 subjects without PTSD (non-PTSD group). Twenty matched adolescents were recruited from an area that was not affected significantly by the earthquake as the control group. Hair cortisol concentrations were measured by the electrochemiluminescence immunoassay in each 3-cm segment of hair sample from the scalp. RESULTS: There was no significant difference at the baseline hair cortisol level in the three groups before the traumatic event (p > .6). Hair cortisol levels changed over time and differed among groups (p = .0042). The hair cortisol levels among the PTSD and non-PTSD subjects were elevated, suggesting increasing levels in response to stress. However, these two groups differed in their response. The non-PTSD subjects showed a significantly higher cortisol level than the PTSD group between month 2 and month 4 (p = .0137) and also between month 5 and month 7 (p = .0438) after the traumatic event. CONCLUSIONS: This study revealed a blunted response curve to the disaster among PTSD subjects compared with subjects without PTSD. These findings suggest that hair cortisol level could be used to assess the integrated hypothalamic-pituitary-adrenal activity over a period of months after traumatic events and be used to serve as a biomarker in patients with PTSD. PMID- 22305288 TI - Prospective study on the effect of shirt sleeves and ties on the transmission of bacteria to patients. AB - Costs associated with hospital-acquired infections lead to policies aimed at decreasing their incidence. Clothing restrictions are often implemented in response, but they are based on little scientific evidence. This study is a prospective, controlled investigation of the effect of shirt sleeves and ties on the transmission of bacteria from doctors to patients. Results show that wearing an unsecured tie results in greater transmission, but that sleeve length does not affect transmission rate. The design is a possible model for further controlled experiments to fill the evidence gap regarding the transmission of micro organisms from healthcare workers to patients. PMID- 22305289 TI - Estimates and influences of reflective opposite-sex norms on alcohol use among a high-risk sample of college students: exploring Greek-affiliation and gender effects. AB - Reflective opposite sex norms are behavior that an individual believes the opposite sex prefers them to do. The current study extends research on this recently introduced construct by examining estimates and influences of reflective norms on drinking in a large high-risk heterosexual sample of male and female college students from two universities. Both gender and Greek-affiliation served as potential statistical moderators of the reflective norms and drinking relationship. All participants (N=1790; 57% female) answered questions regarding the amount of alcohol they believe members of the opposite sex would like their opposite sex friends, dates, and sexual partners to drink. Participants also answered questions regarding their actual preferences for drinking levels in each of these three relationship categories. Overall, women overestimated how much men prefer their female friends and potential sexual partners to drink, whereas men overestimated how much women prefer their sexual partners to drink. Greek affiliated males demonstrated higher reflective norms than non-Greek males across all relationship categories, and for dating partners, only Greek-affiliated males misperceived women's actual preferences. Among women however, there were no differences between reflective norm estimates or the degree of misperception as a function of Greek status. Most importantly, over and above perceived same-sex social norms, higher perceived reflective norms tended to account for greater variance in alcohol consumption for Greeks (vs. non-Greeks) and males (vs. females), particularly within the friend and sexual partner contexts. The findings highlight that potential benefits might arise if existing normative feedback interventions were augmented with reflective normative feedback designed to target the discrepancy between perceived and actual drinking preferences of the opposite sex. PMID- 22305290 TI - A theoretical and non-destructive experimental approach for direct inclusion of measured collagen orientation and recruitment into mechanical models of the artery wall. AB - Gradual collagen recruitment has been hypothesized as the underlying mechanism for the mechanical stiffening with increasing stress in arteries. In this work, we investigated this hypothesis in eight rabbit carotid arteries by directly measuring the distribution of collagen recruitment stretch under increasing circumferential loading using a custom uniaxial (UA) extension device combined with a multi-photon microscope (MPM). This approach allowed simultaneous mechanical testing and imaging of collagen fibers without traditional destructive fixation methods. Fiber recruitment was quantified from 3D rendered MPM images, and fiber orientation was measured in projected stacks of images. Collagen recruitment was observed to initiate at a finite strain, corresponding to a sharp increase in the measured mechanical stiffness, confirming the previous hypothesis and motivating the development of a new constitutive model to capture this response. Previous constitutive equations for the arterial wall have modeled the collagen contribution with either abrupt recruitment at zero strain, abrupt recruitment at finite strain or as gradual recruitment beginning at infinitesimal strain. Based on our experimental data, a new combined constitutive model was presented in which fiber recruitment begins at a finite strain with activation stretch represented by a probability distribution function. By directly including this recruitment data, the collagen contribution was modeled using a simple Neo Hookean equation. As a result, only two phenomenological material constants were required from the fit to the stress stretch data. Three other models for the arterial wall were then compared with these results. The approach taken here was successful in combining stress-strain analysis with simultaneous microstructural imaging of collagen recruitment and orientation, providing a new approach by which underlying fiber architecture may be quantified and included in constitutive equations. PMID- 22305291 TI - Evolutionary and functional analyses of the interaction between the myeloid restriction factor SAMHD1 and the lentiviral Vpx protein. AB - SAMHD1 has recently been identified as an HIV-1 restriction factor operating in myeloid cells. As a countermeasure, the Vpx accessory protein from HIV-2 and certain lineages of SIV have evolved to antagonize SAMHD1 by inducing its ubiquitin-proteasome-dependent degradation. Here, we show that SAMHD1 experienced strong positive selection episodes during primate evolution that occurred in the Catarrhini ancestral branch prior to the separation between hominoids (gibbons and great apes) and Old World monkeys. The identification of SAMHD1 residues under positive selection led to mapping the Vpx-interaction domain of SAMHD1 to its C-terminal region. Importantly, we found that while SAMHD1 restriction activity toward HIV-1 is evolutionarily maintained, antagonism of SAMHD1 by Vpx is species-specific. The distinct evolutionary signature of SAMHD1 sheds light on the development of its antiviral specificity. PMID- 22305292 TI - [Health workforce planning and training, with emphasis on primary care. SESPAS Report 2012]. AB - The present article provides an overview of workforce planning for health professionals in Spain, with emphasis on physicians and primary care. We analyze trends, describe threats and make some suggestions. In Spain some structural imbalances remain endemic, such as the low number of nurses with respect to physicians, which may become a barrier to needed reforms. The new medical degree, with the rank of master, will not involve major changes to training. Nursing, which will require a university degree, leaves a gap that will be filled by nursing assistants.This domino effect ends in family medicine, which has no upgrading potential. Hence reasonable objectives for the system are to prioritize the post-specialization training of family physicians, enhance their research capacity and define a career that does not equate productivity with seniority. What is undergoing a crisis of identity and prestige is family medicine, not primary care. There is a risk that the specialty of family medicine will lose rank after the specialty of emergency medicine is approved. Today, about 40% of emergency physicians in the public network are specialists, most of them in family medicine. In 2010 a new fact emerged: an elite of foreign doctors obtained positions as resident medical interns in highly sought-after specialties through the national competitive examination. This phenomenon should be closely monitored and requires Spain to define the pattern of internationalization of health professionals in a clear and precise model. PMID- 22305293 TI - Identification of avian wax synthases. AB - BACKGROUND: Bird species show a high degree of variation in the composition of their preen gland waxes. For instance, galliform birds like chicken contain fatty acid esters of 2,3-alkanediols, while Anseriformes like goose or Strigiformes like barn owl contain wax monoesters in their preen gland secretions. The final biosynthetic step is catalyzed by wax synthases (WS) which have been identified in pro- and eukaryotic organisms. RESULTS: Sequence similarities enabled us to identify six cDNAs encoding putative wax synthesizing proteins in chicken and two from barn owl and goose. Expression studies in yeast under in vivo and in vitro conditions showed that three proteins from chicken performed WS activity while a sequence from chicken, goose and barn owl encoded a bifunctional enzyme catalyzing both wax ester and triacylglycerol synthesis. Mono- and bifunctional WS were found to differ in their substrate specificities especially with regard to branched-chain alcohols and acyl-CoA thioesters. According to the expression patterns of their transcripts and the properties of the enzymes, avian WS proteins might not be confined to preen glands. CONCLUSIONS: We provide direct evidence that avian preen glands possess both monofunctional and bifunctional WS proteins which have different expression patterns and WS activities with different substrate specificities. PMID- 22305294 TI - Comparison of cement pressurisation in flanged and unflanged acetabular cups. AB - BACKGROUND: This biomechanical study examined difference in cement pressures generated by flanged and unflanged acetabular cups in hip arthroplasty. METHOD: Using a model acetabulum, cement was inserted and pressurised followed by cup insertion and pressurisation. Pressures were recorded using transducers in the acetabulum. We compared Charnley Ogee (flanged), Exeter contemporary (flanged) and Exeter low profile (unflanged) cups using Simplex and CMW1 cements in turn. RESULTS: Using Simplex, Charnley Ogee cup generated highest initial peak pressure and overall mean pressure. Exeter unflanged cup generated higher initial and mean pressures compared to Exeter flanged cup. With CMW, there was no significant difference between the pressures generated by the cups. CONCLUSIONS: Our experiment suggests that flanged cups do not consistently generate significantly higher cement pressures compared to unflanged cups. PMID- 22305295 TI - Impact of tissue volume and purification on clinical autologous islet transplantation for the treatment of chronic pancreatitis. AB - Autologous islet transplantation after total pancreatectomy is an excellent treatment for painful chronic pancreatitis. Traditionally, islets have been isolated without purification; however, purification is applied when the tissue volume is large. Nevertheless, the impact of tissue volume and islet purification on clinical outcomes of autologous islet transplantation has not been well examined. We analyzed 27 cases of autologous islet transplantation performed from October 2006 to January 2011. After examining the relationship between tissue volume and portal pressure at various time points, we compared islet characteristics and clinical outcomes between cases with complications (complication group) and without (noncomplication group), as well as cases with purification (purification group) and without (nonpurification group). Tissue volume significantly correlated with maximum (R = 0.61), final (R = 0.53), and delta (i.e., difference between base and maximum; R = 0.71) portal pressure. The complication group had a significantly higher body mass index, tissue volume, islet yield, and portal pressure (maximum, final, delta), suggesting that complications were associated with high tissue volume and high portal pressure. Only one of four patients (25%) in the complication group became insulin free, whereas 11 of 23 patients (49%) in the noncomplication group became insulin free with smaller islet yields. The purification group had a higher islet yield and insulin independence rate but had similar final tissue volume, portal pressure, and complication rates compared with the nonpurification group. In conclusion, high tissue volume was associated with high portal pressure and complications in autologous islet transplantation. Islet purification effectively reduced tissue volume and had no negative impact on islet characteristics. Therefore, islet purification can reduce the risk of complications and may improve clinical outcome for autologous islet transplantation when tissue volume is large. PMID- 22305296 TI - In vitro and in vivo acaricidal activity of a herbal extract. AB - The anti-tick efficacy of combined aqueous herbal extracts of Azadirachta indica leaves, Nicotiana tabacum leaves, Calotropis procera flowers and Trachyspermum ammi seeds was evaluated using adult immersion test, larval packet test and ear bag method. The extract exhibited lethal effects on egg laying (index of egg laying=0.371404+/-0.00435), hatching (22.35%) and total larval mortality at 50 mg ml(-1) and reduced tick intensity on the infested calves (18 detached out of 35 at 45% (w/w) suspension, topically applied). The herbal extract exerted dose- and time-dependent response against all the developmental stages of Rhipicephalus (Boophilus) microplus considered in this study, thus justified their use in the traditional system of Pakistan. PMID- 22305297 TI - Re-emergence of Babesia conradae and effective treatment of infected dogs with atovaquone and azithromycin. AB - Babesia conradae (B. conradae) causes hemolytic anemia in dogs. This organism has not been reported clinically since it was originally described in southern California in 1991. To date, no anti-protozoal therapies have been associated with clearance of B. conradae. This report describes the use of atovaquone and azithromycin for the treatment of dogs naturally infected with B. conradae and report the re-emergence of B. conradae in southern California. Twelve dogs naturally infected with B. conradae were identified by practicing veterinarians and public health officials in southern California. Treatments consisted of a 10 day course of atovaquone (13.3mg/kg PO q 8h) and azithromycin (10-12.5mg/kg PO q 24h). Four dogs were treated in a randomized blinded placebo-controlled fashion, four additional cases were treated in a non-random, non-blinded fashion and one dog received no treatment. All dogs were tested for B. conradae DNA by polymerase chain reaction (PCR) initially and then once or 3 times post treatment (60-210 days). B. conradae infected dogs that received treatment did not have any detectable Babesia DNA by PCR after treatment. In contrast, dogs receiving placebo had detectable Babesia DNA by PCR throughout the study period. Combination therapy with atovaquone and azithromycin appears to be effective for acute and chronic babesiosis caused by B. conradae. PMID- 22305298 TI - Clinical outcomes after arthroscopic psoas lengthening: the effect of femoral version. AB - PURPOSE: The purpose of this study was to examine the association between femoral anteversion and clinical outcomes after arthroscopic lengthening of a symptomatic, snapping psoas tendon in young patients. METHODS: Sixty-seven consecutive patients with symptomatic coxa saltans underwent arthroscopic psoas tendon lengthening through a transcapsular approach during a 3-year period by a single arthroscopic hip surgeon. Demographic and clinical variables were collected. Patients were divided into low/normal femoral version and high femoral version groups and analyzed for association of femoral version with clinical outcomes as measured by the modified Harris Hip Score (mHHS) and Hip Outcome Score (HOS) preoperatively and postoperatively with a minimum of 6 months' follow up (range, 6 to 24 months). Two-sample t tests were used for data analysis, with P < .05 defined as significant. RESULTS: Preoperative evaluation showed excessive anteversion (>25 degrees ) associated with worse HOS sports subscale scores (26.6 v 50.0 for excessive v low/normal anteversion, P = .013) and no difference in mHHS and HOS activities-of-daily living subscale scores. Postoperative mHHS scores were significantly different (76.9 v 86.1 for excessive v low/normal anteversion, P = .031). No association was noted between clinical outcome measures and any other clinical or demographic variable (P > .05). CONCLUSIONS: Patients with increased femoral anteversion may be at greater risk for inferior clinical outcomes after arthroscopic lengthening of a symptomatic, snapping psoas tendon. The psoas tendon may be an important passive and dynamic stabilizer of the hip in these patients, and release may result in a greater alteration of kinematics with high-demand activities, particularly terminal extension and external rotation when the tendon is typically at its highest tension. These results may help surgeons identify which patients may be at risk for inferior clinical outcome after psoas lengthening. PMID- 22305299 TI - Graft size and patient age are predictors of early revision after anterior cruciate ligament reconstruction with hamstring autograft. AB - PURPOSE: To evaluate whether decreased hamstring autograft size and decreased patient age are predictors of early graft revision. METHODS: Of 338 consecutive patients undergoing primary anterior cruciate ligament (ACL) reconstruction with hamstring autograft, 256 (75.7%) were evaluated. Graft size and patient age, gender, and body mass index at the time of ACL reconstruction were recorded, along with whether subsequent ACL revision was performed. RESULTS: The 256 patients comprised 136 male and 120 female patients and ranged in age from 11 to 52 years (mean, 25.0 years). The mean follow-up was 14 months (range, 6 to 47 months). Revision ACL reconstruction was performed in 18 of 256 patients (7.0%) at a mean of 12 months after surgery (range, 3 to 31 months). Revision was performed in 1 of 58 patients (1.7%) with grafts greater than 8 mm in diameter, 9 of 139 patients (6.5%) with 7.5- or 8-mm-diameter grafts, and 8 of 59 patients (13.6%) with grafts 7 mm or less in diameter (P = .027). There was 1 revision performed in the 137 patients aged 20 years or older (0.7%), but 17 revisions were performed in the 119 patients aged under 20 years (14.3%) (P < .0001). Most revisions (16 of 18) were noted to occur in patients aged under 20 years with grafts 8 mm in diameter or less, and the revision rate in this population was 16.4% (16 of 97 patients). Age less than 20 years at reconstruction (odds ratio [OR], 18.97; 95% confidence interval [CI], 2.43 to 147.06; P = .005), decreased graft size (OR, 2.20; 95% CI, 1.00 to 4.85; P = .05), and increased follow-up time (OR, 1.07; 95% CI, 1.02 to 1.12) were associated with increased risk of revision. CONCLUSIONS: Decreased hamstring autograft size and decreased patient age are predictors of early graft revision. Use of hamstring autografts 8 mm in diameter or less in patients aged under 20 years is associated with higher revision rates. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 22305300 TI - Survey of infections transmissible between baboons and humans, Cape Town, South Africa. AB - Baboons on South Africa's Cape Peninsula come in frequent contact with humans. To determine potential health risks for both species, we screened 27 baboons from 5 troops for 10 infections. Most (56%) baboons had antibodies reactive or cross reactive to human viruses. Spatial overlap between these species poses low but potential health risks. PMID- 22305301 TI - Clinical experience with power-injectable PICCs in intensive care patients. AB - INTRODUCTION: In the ICU, peripherally inserted central catheters (PICCs) may be an alternative option to standard central venous catheters, particularly in patients with coagulation disorders or at high risk for infection. Some limits of PICCs (such as low flow rates) may be overcome with the use of power-injectable catheters. METHODS: We retrospectively reviewed all of the power-injectable PICCs inserted in adult and pediatric patients in the ICU during a 12-month period, focusing on the rate of complications at insertion and during maintenance. RESULTS: We collected 89 power-injectable PICCs (in adults and in children), both multiple and single lumen. All insertions were successful. There were no major complications at insertion and no episodes of catheter-related bloodstream infection. Non-infective complications during management were not clinically significant. There was one episode of symptomatic thrombosis during the stay in the ICU and one episode after transfer of a patient to a non-intensive ward. CONCLUSION: Power-injectable PICCs have many advantages in the ICU: they can be used as multipurpose central lines for any type of infusion including high-flow infusion, for hemodynamic monitoring, and for high-pressure injection of contrast media during radiological procedures. Their insertion is successful in 100% of cases and is not associated with significant risks, even in patients with coagulation disorders. Their maintenance is associated with an extremely low rate of infective and non-infective complications. PMID- 22305302 TI - Transcriptome profiling of a curdlan-producing Agrobacterium reveals conserved regulatory mechanisms of exopolysaccharide biosynthesis. AB - BACKGROUND: The ability to synthesize exopolysaccharides (EPS) is widespread among microorganisms, and microbial EPS play important roles in biofilm formation, pathogen persistence, and applications in the food and medical industries. Although it is well established that EPS synthesis is invariably in response to environmental cues, it remains largely unknown how various environmental signals trigger activation of the biochemical synthesis machinery. RESULTS: We report here the transcriptome profiling of Agrobacterium sp. ATCC 31749, a microorganism that produces large amounts of a glucose polymer known as curdlan under nitrogen starvation. Transcriptome analysis revealed a nearly 100 fold upregulation of the curdlan synthesis operon upon transition to nitrogen starvation, thus establishing the prominent role that transcriptional regulation plays in the EPS synthesis. In addition to known mechanisms of EPS regulation such as activation by c-di-GMP, we identify novel mechanisms of regulation in ATCC 31749, including RpoN-independent NtrC regulation and intracellular pH regulation by acidocalcisomes. Furthermore, we show evidence that curdlan synthesis is also regulated by conserved cell stress responses, including polyphosphate accumulation and the stringent response. In fact, the stringent response signal, pppGpp, appears to be indispensible for transcriptional activation of curdlan biosynthesis. CONCLUSIONS: This study identifies several mechanisms regulating the synthesis of curdlan, an EPS with numerous applications. These mechanisms are potential metabolic engineering targets for improving the industrial production of curdlan from Agrobacterium sp. ATCC 31749. Furthermore, many of the genes identified in this study are highly conserved across microbial genomes, and we propose that the molecular elements identified in this study may serve as universal regulators of microbial EPS synthesis. PMID- 22305303 TI - The classical dichotomy between presentation of endogenous antigens via the MHC class I pathway and exogenous antigens via the MHC class-II pathway. PMID- 22305305 TI - Routine exposure to blood within hostel environments might help to explain elevated levels of hepatitis C amongst homeless drug users: insights from a qualitative study. AB - BACKGROUND: Although homelessness is a risk factor for HCV infection, there is a lack of research exploring the relationship between living in a hostel for homeless people and blood-borne viruses. The tendency to focus on risky injecting practices and HCV has also eclipsed the transmission risks potentially posed by spilt and dried blood. METHODS: Semi-structured qualitative interviews were conducted with 40 homeless drug users (HDUs) (29 men and 11 women). The aim of the study was to explore the support needs of HDUs staying in emergency hostels or night shelters, but blood emerged as an unexpected recurring topic within participants' accounts. Accordingly, all blood data were coded and analysed inductively. RESULTS: Participants reported that spilt and dried blood were routine features of hostel life, particularly in larger night shelters. Given that the hepatitis C virus can survive outside the human body for several weeks and even months, this poses a worrying but largely overlooked transmission risk. According to the HDUs interviewed, hostel providers were often slow to remove blood and other bodily waste, leaving residents to clean it themselves or to avoid soiled areas. CONCLUSIONS: The routine presence of blood within hostel environments might help to explain elevated levels of HCV amongst homeless drug users. However, there is a need for robust quantitative and qualitative research to systematically test and explore associations between HCV and hostel life. Recommendations are made for improving hostel cleanliness, apprising hostel staff and residents of HCV and other blood-borne virus transmission risks, and ensuring that blood and other bodily waste are deemed unacceptable features of any hostel setting. PMID- 22305304 TI - Making memory at birth: understanding the differentiation of natural killer T cells. AB - Glycolipid reactive natural killer T cells with an invariant TCR alpha-chain (iNKT cells) are a conserved population of T lymphocytes with a distinct anatomical distribution and functional properties. The differentiation pathway of iNKT cells branches off from mainstream thymocyte differentiation at the double positive stage, and recent work has revealed how signaling events early in the iNKT cell pathway imprint a memory-like behavior on these cells. Additionally, unique molecular interactions governing iNKT cell development and tissue distribution have been uncovered recently, building up our knowledge of the complex network of interactions that form this population. Novel autologous antigens for these cells have been identified, although it has not yet been resolved if there is single endogenous antigen responsible for both positive selection and/or peripheral activation. PMID- 22305306 TI - Increased phase synchronization during continuous face integration measured simultaneously with EEG and fMRI. AB - OBJECTIVE: Gamma zero-lag phase synchronization has been measured in the animal brain during visual binding. Human scalp EEG studies used a phase locking factor (trial-to-trial phase-shift consistency) or gamma amplitude to measure binding but did not analyze common-phase signals so far. This study introduces a method to identify networks oscillating with near zero-lag phase synchronization in human subjects. METHODS: We presented unpredictably moving face parts (NOFACE) which - during some periods - produced a complete schematic face (FACE). The amount of zero-lag phase synchronization was measured using global field synchronization (GFS). GFS provides global information on the amount of instantaneous coincidences in specific frequencies throughout the brain. RESULTS: Gamma GFS was increased during the FACE condition. To localize the underlying areas, we correlated gamma GFS with simultaneously recorded BOLD responses. Positive correlates comprised the bilateral middle fusiform gyrus and the left precuneus. CONCLUSIONS: These areas may form a network of areas transiently synchronized during face integration, including face-specific as well as binding specific regions and regions for visual processing in general. SIGNIFICANCE: Thus, the amount of zero-lag phase synchronization between remote regions of the human visual system can be measured with simultaneously acquired EEG/fMRI. PMID- 22305307 TI - Recombination of human coxsackievirus B5 in hand, foot, and mouth disease patients, China. PMID- 22305308 TI - Ergonomics: back to the future. PMID- 22305309 TI - Aspheric multifocal intraocular lens. PMID- 22305310 TI - Paradoxical embolus and endophthalmitis. PMID- 22305311 TI - Streptococcal orbital abscesses. PMID- 22305312 TI - Residency interview video conferencing. PMID- 22305313 TI - Resident cataract surgery. PMID- 22305314 TI - Glaucoma clinical guidelines. PMID- 22305316 TI - Confocal microscopy. PMID- 22305319 TI - Photoreceptor imaging. PMID- 22305321 TI - Bevacizumab for ROP. PMID- 22305322 TI - Smartphone fundoscopy. PMID- 22305325 TI - Management of obesity in the National Health and Nutrition Examination Survey (NHANES), 2007-2008. AB - PURPOSE: The prevalence of obesity has been increasing in the United States. We set out to investigate the use of pharmacologic and non-pharmacologic therapy for the treatment of obesity in recent years. METHODS: We included 2630 men and 2702 women who took part in the National Health and Nutrition Examination Survey from 2007 to 2008. We analyzed their demographic and anthropometric data and their weight and drug history. RESULTS: A total of 45.9% of men and 45.0% of women were candidates for treatment (body mass index >=30 kg/m(2), or >=27 kg/m(2) with risk factors). Among these participants, 85.1% considered themselves overweight, 90.1% would like to lose weight, 61.9% had dietary changes, 36.5% exercised, 3.7% took nonprescription drugs, and 2.2% took prescription drugs to control weight during the preceding year. During the preceding month, 0.5% and 0.1% of participants were taking phentermine and orlistat, respectively. There were no participants on sibutramine. CONCLUSIONS: Although obesity is highly prevalent, only a small percentage of obese Americans are on anti-obesity medication. The withdrawal of sibutramine would have minimal impact on the general population. There is a need for more lifestyle changes in the majority of obese individuals. PMID- 22305326 TI - Accidental perforation of the lateral femoral cortex in ACL reconstruction: an investigation of mechanical properties of different fixation techniques. AB - PURPOSE: The aim of this study was to evaluate the mechanical properties of anterior cruciate ligament (ACL) reconstruction using the medial portal technique with cortical fixation and hybrid fixation after penetration of the lateral cortex by use of different drill sizes. METHODS: In this biomechanical study a porcine in vitro model was used. The testing protocol consisted of a cyclic loading protocol (1,000 cycles, 50 and 250 N) and subsequent ultimate failure testing. Number of cyclic loadings survived, stiffness, yield load, maximum load, and graft elongation, as well as failure mode, were analyzed after ACL reconstruction with 5- to 9-mm soft-tissue grafts. In the control group, conventional penetration of the lateral cortex with a 4.5-mm drill and cortical fixation were performed. In the tested groups, the lateral cortex was penetrated with a drill matching the graft size. In the first part of the study, we used cortical fixation. In the second part, we used hybrid fixation with an interference screw. RESULTS: In the first part of the study, ACL reconstruction with 5- to 6-mm perforation of the lateral cortex showed no significant differences in ultimate failure load after cyclic loading compared with the control group (P > .05). Specimens with reconstruction with 7- to 9-mm perforation of the lateral cortex and cortical fixation did not survive the cyclic loading protocol. In the second part of the study, with a hybrid fixation technique, ultimate failure testing after cyclic loading of specimens with 7- to 9-mm penetration showed no significant differences in tested parameters compared with the control group (P > .05). CONCLUSIONS: After penetration of the lateral cortex with a drill size of more than 6 mm, cortical ACL fixation results in poor mechanical properties. Hybrid fixation increases the mechanical properties significantly after penetration with a 7- to 9-mm drill. CLINICAL RELEVANCE: We advise caution to avoid penetration of the lateral femoral cortex when using cortical flip-button fixation. In case of accidental perforation of the lateral cortex with a diameter greater than 6 mm, we recommend performing hybrid fixation. PMID- 22305327 TI - The role of subacromial decompression in patients undergoing arthroscopic repair of full-thickness tears of the rotator cuff: a systematic review and meta analysis. AB - PURPOSE: The purpose of this study was to determine the efficacy of arthroscopic repair of full-thickness rotator cuff tears with and without subacromial decompression. METHODS: We searched the Cochrane Central Register of Controlled Trials (third quarter of 2011), Medline (1948 to week 1 of September 2011), and Embase (1980 to week 37 of 2011) for eligible randomized controlled trials. Two reviewers selected studies for inclusion, assessed methodologic quality, and extracted data. Pooled analyses were performed by use of a random effects and relative risk model with computation of 95% confidence intervals. RESULTS: We included 4 randomized trials and 373 patients. Methodologic quality was variable as assessed by the CLEAR NPT (Checklist to Evaluate a Report of a Non pharmacological Trial) tool. One trial showed that there was no difference in disease-specific quality of life (Western Ontario Rotator Cuff questionnaire) between the 2 treatment groups. A meta-analysis of shoulder-specific outcome measures (American Shoulder and Elbow Surgeons or Constant scores) or the rate of reoperation between patients treated with subacromial decompression and those treated without it also showed no statistically significant differences. CONCLUSIONS: On the basis of the currently available literature, there is no statistically significant difference in subjective outcome after arthroscopic rotator cuff repair with or without acromioplasty at intermediate follow-up. LEVEL OF EVIDENCE: Level I, systematic review of Level I studies. PMID- 22305328 TI - Circadian changes in cortical excitability in restless legs syndrome. AB - Various investigations have revealed a widespread and somewhat controversial pattern of cerebral, cerebellar and brainstem involvement in the pathophysiology of restless legs syndrome (RLS). However, several studies which investigated functional or structural aspects indicated cortical involvement in RLS. In this study, we aimed to analyze circadian changes of cortical excitability in idiopathic RLS patients by means of transcranial magnetic stimulation (TMS). Eleven idiopathic RLS patients and eight healthy age and sex matched subjects were investigated using single-pulse TMS and motor nerve conduction studies during early afternoon when there were no symptoms and late at night (22:00 23:00) when the symptoms reappeared. Central motor conduction time, latencies and amplitudes of scalp and cervical motor evoked potentials, resting and active motor thresholds, and cortical silent period were measured. Measured parameters were similar between RLS patients and healthy subjects during the daytime. At night, cortical silent periods tended to shorten, and motor thresholds tended to decrease in the RLS group, whereas in controls they tended to increase. At night, active motor-threshold measurements were significantly lower in the RLS group (28.5 +/- 6.2% vs 40.4 +/- 8.4%, p=0.006). Therefore, we propose that in patients with RLS, conduction along the motor corticospinal axons is normal, with the possible loss of subcortical inhibition at nighttime. PMID- 22305329 TI - The Canadian Triage and Acuity Scale for children: a prospective multicenter evaluation. AB - STUDY OBJECTIVE: The aims of the study are to measure both the interrater agreement of nurses using the Canadian Triage and Acuity Scale in children and the validity of the scale as measured by the correlation between triage level and proxy markers of severity. METHODS: This was a prospective multicenter study of the reliability and construct validity of the Canadian Triage and Acuity Scale in 9 tertiary care pediatric emergency departments (EDs) across Canada during 2009 to 2010. Participants were a sample of children initially triaged as Canadian Triage and Acuity Scale level 2 (emergency) to level 5 (nonurgent). Participants were recruited immediately after their initial triage to undergo a second triage assessment by the research nurse. Both triages were performed blinded to the other. The primary outcome measures were the interrater agreement between the 2 nurses and the association between triage level and hospitalization. Secondary outcome measures were the association between triage level and health resource use and length of stay in the ED. RESULTS: A total of 1,564 patients were approached and 1,464 consented. The overall interrater agreement was good, as demonstrated by a quadratic weighted kappa score of 0.74 (95% confidence interval 0.71 to 0.76). Hospitalization proportions were 30%, 8.3%, 2.3%, and 2.2% for patients triaged at levels 2, 3, 4, and 5, respectively. There was also a strong association between triage levels and use of health care resources and length of stay. CONCLUSION: The Canadian Triage and Acuity Scale demonstrates a good interrater agreement between nurses across multiple pediatric EDs and is a valid triage tool, as demonstrated by its good association with markers of severity. PMID- 22305330 TI - Frequent users of emergency departments: developing standard definitions and defining prominent risk factors. AB - STUDY OBJECTIVE: We identify factors that define frequent and highly frequent emergency department (ED) users. METHODS: Administrative health care records were used to define less frequent (1 to 6 visits), frequent (7 to 17 visits), and highly frequent (>=18 visits) ED users. Analyses were conducted to determine the most unique demographic, disease, and health care use features of these groups. RESULTS: Frequent users composed 9.9% of all ED visits, whereas highly frequent users composed 3.6% of visits. Compared with less frequent users, frequent users were defined most strongly by their substance abuse challenges and by their many visits to primary care and specialist physicians. Substance abuse also distinguished highly frequent from frequent ED users strongly; 67.3% versus 35.9% of these patient groups were substance abusers, respectively. Also, 70% of highly frequent versus only 17.8% of frequent users had a long history of frequent ED use. Last, highly frequent users did not use other health care services proportionally more than their frequent user counterparts, suggesting that these former patients use EDs as a main source of care. CONCLUSION: This research develops objective thresholds of frequent and highly frequent ED use. Although substance abuse is prominent in both groups, only highly frequent users seem to visit EDs in place of other health care services. Future analyses can investigate these patterns of health care use more closely, including how timely access to primary care affects ED use. Cluster analysis also has value for defining frequent user subgroups who may benefit from different yet equally effective treatment options. PMID- 22305331 TI - Detection and diagnostic value of urine leucine-rich alpha-2-glycoprotein in children with suspected acute appendicitis. AB - STUDY OBJECTIVE: Previously, we used a proteomics approach for the discovery of new diagnostic markers of acute appendicitis and identified leucine-rich alpha-2 glycoprotein (LRG) that was elevated in the urine of children with acute appendicitis and enriched in diseased appendices. Here, we sought to evaluate the diagnostic utility of enzyme-linked immunosorbent assay (ELISA) of urine LRG in a blinded, prospective, cohort study of children being evaluated for acute abdominal pain. METHODS: Urine LRG concentration was measured with a commercially available LRG ELISA and selected ion monitoring mass spectrometry. Urine LRG test performance was evaluated blindly against the pathologic diagnosis and histologic grade of appendicitis. RESULTS: Urine LRG was measured in 49 patients. Mean urine LRG concentration measured with commercial LRG ELISA was significantly elevated in patients with acute appendicitis but exhibited an interference effect. Direct measurements using selected ion monitoring mass spectrometry demonstrated that LRG was elevated more than 100-fold in patients with acute appendicitis compared with those without, with the receiver operating characteristic area under the curve of 0.98 (95% confidence interval 0.96 to 1.0). Among patients with acute appendicitis, elevations of urine LRG measured with ELISA and selected ion monitoring mass spectrometry correlated with the histologic severity of appendicitis. CONCLUSION: Urine LRG ELISA allows for discrimination between patients with and without acute appendicitis but exhibits limited accuracy because of immunoassay interference. Direct measurements of urine LRG with selected ion monitoring mass spectrometry demonstrate superior diagnostic performance. Development of a clinical-grade urine LRG assay is needed to advance the diagnostic accuracy of clinical evaluations of appendicitis. PMID- 22305332 TI - Can procalcitonin levels guide antibiotic therapy in bacterial infections and reduce antibiotic overconsumption without having a negative effect on clinical outcomes? PMID- 22305333 TI - Emergency department death from systemic loxoscelism. AB - Systemic loxoscelism is a constitutional illness resulting from the bite of the brown recluse spider. In severe form, it may cause hemolysis, acute renal failure, and disseminated intravascular coagulation. More rarely, it may result in death. We report an unusual case of systemic loxoscelism resulting in death less than one day following envenomation. We also discuss screening algorithms and contemporary management of systemic loxoscelism. PMID- 22305334 TI - New insights about the early diagnosis of fertility impairment in varicoceles: the DNA repair gene example. AB - Of all men consulted for infertility, around 30% appear to have a varicocele, therefore, this male dysfunction has been considered as a potential cause of infertility in many patients. Emerging studies point out spermatozoa progressive motility as the most important predictor of fertility provided that the analysis was carried out with infertility duration, thus leaving unsolved problem to evaluate the spontaneous testicular damage during the very early phase in varicoceles. Given the deterioration of testicular function caused by varicoceles is progressive, the early and efficient evaluation of testicular damage would be of great importance for the future medical intervention in this population. The resultant mechanism by which varicoceles affect testicular function remains unclear, but the increase in testicular temperature is most commonly accepted aetiology. In this context, we hypothesize that metastasis-associated protein 1 (MTA1), an intrinsic DNA damage response component, possessing transient protective effect in primary spermatocytes against heat stress, bears the potential to be a diagnostic biomarker for the assessment of early testicular damage in varicoceles. The facet that the decrease of MTA1 expression appears much earlier than the beginning of apoptotic wave after heat stress warrants its theoretical rationality and technical accessibility for biochemical application. Basically, MTA1 participates in the maintenance of early apoptotic balance induced by hyperthermal stimulation by elevating the deacetylation level of p53, a master regulator responsible for the initial phase of germ cell apoptosis induced by hyperthermia. These knowledges collectively promote our belief that information from future experiments designed to further study MTA1 during spermatogenesis will provide a scientific basis for the development of a novel biomarker for early diagnosis of testicular detriment in varicoceles, which should lead to improved outcomes in this progressive pathology. PMID- 22305335 TI - Blood flow restriction: rationale for improving bone. AB - Low intensity exercise with blood flow restriction has been shown to increase muscle hypertrophy and strength similar to high intensity resistance exercise. Interestingly, low intensity resistance exercise to failure has shown the same muscle protein synthesis response as higher intensity exercise, questioning the need for blood flow restriction during low intensity exercise. The purpose of this manuscript is to discuss the mechanisms and potential benefits of blood flow restricted exercise on bone adaptation and provide rationale as to why low load resistance exercise to failure would be unlikely to produce these benefits. The studies completed thus far support the hypothesis that training with blood flow restriction may provide not only a novel modality to induce adaptation in muscle but also bone, which was previously thought to only occur with higher intensity/impact exercise. We hypothesize that the main mechanism behind the proposed favorable bone responses observed thus far is through increased intramedullary pressure and interstitial fluid flow within the bone caused by venous occlusion. Therefore, although similar muscular benefits may be observed from low intensity exercise performed to failure (e.g. strength, hypertrophy, and endurance), the response of bone might be different, highlighting the potential importance of the blood flow restriction stimulus. PMID- 22305336 TI - Extreme preconditioning: cold adaptation through sea swimming as a means to improving surgical outcomes. AB - The practice of sea bathing for its health benefits was popularised by Richard Russell in Regency Brighton during the 18th Century. Although the cures he claimed it could effect seem a little far-fetched today, as with many historical remedies, there is much to be gained from revisiting such theories in the light of modern medical research. In this paper I will draw parallels between the surgical stress response and the response to cold exposure and hypothesise how a programme of sea bathing may be used to enhance postoperative recovery and reduce preoperative complications. PMID- 22305337 TI - Molecular detection and characterization of Anaplasma phagocytophilum strains. AB - The zoonotic rickettsial pathogen Anaplasma phagocytophilum has a broad geographic distribution and a high degree of biological and clinical diversity. To investigate the genetic diversity of A. phagocytophilum strains in the Baltic region and Norway, three species of Ixodidae ticks were examined for A. phagocytophilum infection, and two genes of the pathogen genome were analyzed. Analysis of partial 16S rRNA and partial major surface protein (msp4) gene sequences was accomplished through nested PCR and sequence analysis. Strains identified in this study were compared with those originating from other European countries and the United States. Seven 16S rRNA gene variants and fifteen msp4 gene variants of A. phagocytophilum were detected. Nine sequences had unique nucleotide polymorphisms and therefore differed from other A. phagocytophilum sequences previously submitted to GenBank. The present study represents the first molecular characterization of A. phagocytophum strains circulating in Lithuania and describes the strains detected in Ixodes persulcatus ticks in Latvia and Estonia. This is also the first report describing A. phagocytophilum strains isolated from Dermacentor reticulatus ticks. PMID- 22305338 TI - Olfactory ERPs in an odor/visual congruency task differentiate ApoE epsilon4 carriers from non-carriers. AB - Alzheimer's disease (AD) is a progressive, neurodegenerative disorder that impairs memory and semantic processing. AD patients and MCI patients at risk for AD show altered N400 ERP responses to incongruent visual and verbal stimuli. AD patients exhibit neuropathology in olfactory brain areas before cognitive symptoms, suggesting the potential for olfactory processing to reflect early pathology. Despite this, odor congruency has not been examined. We investigated odor-image congruency in older adults at genetic risk for AD. ApoE epsilon4 carriers and non-carriers were screened for anosmia, severe hyposmia, and dementia. Olfactory ERPs were measured 600-1300 ms following odor-image pairs. Odors were each presented once congruently and once incongruently via an olfactometer. Pz amplitude significantly decreased on incongruent trials in e4 carriers. Pz amplitude differences on congruous and incongruous trials were larger in non carriers. Regression indicated that congruency showed very high sensitivity and specificity for correctly classifying epsilon4 carriers from non carriers. PMID- 22305339 TI - Memory defect induced by beta-amyloid plus glutamate receptor agonist is alleviated by catalpol and donepezil through different mechanisms. AB - Our previous studies demonstrate that a non-cholinesterase inhibitor (AChEI) compound catalpol, purified from a traditional Chinese medicinal herb Rehmannia glutinosa, could improve the symptoms and pathological changes in animal and cellular models of memory related neurodegenerative diseases. In this study, we compared catalpol with the most commonly used AChEI donepezil in respect to their mechanism of action on the neurodegenerative changes in an animal model induced by beta-amyloid (Abeta) plus glutamate receptor agonist. It was found that the model mice showed significant deficit in the learning ability and memory in Y maze avoidance test, and meanwhile both donepezil and catalpol greatly improve the learning ability and memory after 2 to 3 months' administration. At the selected doses, donepezil only partially raised the declined brain muscarinic acetylcholine receptor (M receptor) density and choline acetyltransferase (ChAT) activity resulting in these levels still lower than normal control, while catalpol completely retrieved these two parameters. ELISA revealed that catalpol, instead of donepezil, possessed the capability of elevating the declined brain BDNF level of the animal model. The ELISA results on the BDNF protein level was confirmed by quantitative RT-PCR measurement of BDNF mRNA in Abeta25-35-treated primary culture of forebrain neurons. In combination with our previous work, we think the neuroprotective effects of donepezil and catalpol are mediated through different mechanisms. Since BDNF has been proved to be an important intrinsic factor in protecting neurodegenerative diseases, catalpol may be a hopefully effective compound against neurodegenerative changes induced by Abeta and glutamate receptor agonist. PMID- 22305340 TI - Antiproliferative effect of novel platinum(II) and palladium(II) complexes on hepatic tumor stem cells in vitro. AB - Novel platinum and palladium complexes with (2 isopropoxyphenyl)dicyclohexylarsine and (2-methoxyphenyl)dicyclohexylarsine ligands were synthesized and tested on different tumor cells. Adducts with general formula MX(2)L(2) (M = Pt(II), Pd(II); X = Cl or I; L = organoarsenic ligand) were fully characterized. According to the crystallographic data, in all complexes the organoarsenic ligands coordinate the metal center through the arsenic atom only, in a trans arrangement with the halogen atoms. The antiproliferative potential of complexes 1-4 was evaluated in vitro on human tumor cell lines. A markedly biological activity was observed against the chemoresistant hepatic tumor stem cell line, the normal hepatic stem cells and towards the hepatocellular carcinoma (non-stem) cells. The new compounds toxicity is selectively limited in normal liver cells, unlikeness with the oxaliplatin, which displays a more intense effect in normal cells, compared with the two tumor cell lines. The stem cells treatment with compounds 1-4 causes DNA damages; the antimitotic effect of these compounds is based on their genotoxicity and on the capacity to form crosslinks with the DNA interstrand. In the case of platinum complexes 1 and 3 this mechanism gives rise to specific lesions on DNA that induces apoptosis in stem cells, influencing their selectivity in tumor cell growth inhibition. Compounds 1, 2 and 4 display higher activity against tumor stem cells. The novel platinum complexes 1 and 3 are more efficient against tumor stem cells than oxaliplatin, and if used in combination with sorafenib-based monoclonal anticancer therapy, complexes 1, 3 and 4 have the ability to induce superior chemosensitivity relative to sorafenib than the standard platinum-based drug, making them promising candidates for prodrug development. PMID- 22305341 TI - Efficient synthesis and anti-enteroviral activity of 9-arylpurines. AB - To further explore the anti-enteroviral activity of 9-aryl-6-chloropurines, three different series of compounds with a dialkylamino, (alkyl)amido, or oxazolidinone substituent at the aryl ring have been synthesized, in most cases with the aid of microwave-assisted synthesis. The resulting compounds efficiently inhibit Coxsackie virus type B3 (CVB3) replication with EC(50) values varying from 3 to 15 MUM, and with no significant toxicity in Vero cells. The most potent compounds also selectively inhibit the replication of other enteroviruses including Coxsackie virus B4 and Echo virus 11. The cross-resistance studies performed with different 9-aryl-6-chloropurines indicate that they all belong to the same pharmacological family and differ from other CVB3 drugs such as enviroxime. PMID- 22305342 TI - Synthesis of chromeno[3,4-b]indoles as Lamellarin D analogues: a novel DYRK1A inhibitor class. AB - A library of substituted chromeno[3,4-b]indoles was developed as Lamellarin isosters. Synthesis was achieved from indoles after a four-step pathway sequence involving C-3 iodination, a Suzuki cross-coupling reaction, and a one pot deprotection/lactonisation step. Twenty final compounds were tested in order to determine their activity against topoisomerase I and kinases, the two major biological activities of Lamellarins. One newly synthesized derivative exhibited a strong topoisomerase activity comparable to reference compounds such as campthotecin and Lamellarin with only a weak kinase inhibition. Two other lead compounds were identified as new nanomolar DYRK1A inhibitors and several other drugs affected the kinases in the sub-micromolar range. These results will enable us to use the chromeno[3,4-b]indole as a pharmacophore to develop potent treatments for neurological or oncological disorders in which DYRK1A is fully involved. PMID- 22305343 TI - Investigating the relationship between cognitive change and antidepressant response following rTMS: a large scale retrospective study. AB - BACKGROUND: The use of repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression has been studied extensively over the last 15 years. In this time the vast majority of trials included assessment of cognition to determine whether the technique is cognitively safe. However, recent evidence suggests that the assessment of cognition could also have an important role to play in the prediction of antidepressant response. OBJECTIVES: The current study conducted a post hoc analysis of the cognitive data from four clinical trials of rTMS for treatment resistant depression, with an aim to investigate the relationship between early cognitive changes and eventual depression improvement. METHOD: Data from 137 patients were included in the analysis (62 male and 75 female, mean ages 41.86 +/- 11.68 years). The primary outcome measure for all four studies was the Montgomery Asberg Depression Rating Scale (MADRS). Clinical and cognitive assessments were undertaken at baseline, a midtime point, and at endpoint after 4 or 6 weeks of treatment. RESULTS: There was no cognitive deterioration after a treatment course of rTMS across the four depression trials. Initial improvements in performance on immediate visuospatial memory were significantly related to eventual reduction of depression severity, with visuospatial improvement being a significant predictor of degree of eventual improvement in a near significant regression model. CONCLUSIONS: Traditionally cognitive batteries in rTMS trials are designed to provide a broad assessment of neuropsychological functioning across numerous cognitive domains; however, there is growing evidence that cognition may have a very important role to play as an early indicator of antidepressant response. PMID- 22305344 TI - Rebound symptoms following battery depletion in the NIH OCD DBS cohort: clinical and reimbursement issues. AB - OBJECTIVE: Deep brain stimulation (DBS) is a promising treatment for medication refractory obsessive compulsive disorder (OCD); however, there may be neuropsychiatric symptoms from unintended battery failure. BACKGROUND: Previous studies indicated rebound symptoms from impulse generator (IPG) failure in Parkinson's disease, dystonia, and essential tremor. Unique to OCD is that battery failure may precipitate neuropsychiatric symptoms rather than motor symptoms. METHODS: Six patients with medication refractory OCD received implants as part of the previously reported National Institutional Health (NIH) DBS cohort. All available clinical data and adverse event data was reviewed. RESULTS: The average age of cohort was 42.2 years (30-59 years), and the average baseline Y-BOCS score was 33.8 (31-38). All six subjects were observed to have increased OCD symptomatology during IPG failure; however, Y-BOCS scores remained less than pretreatment range, in five subjects. One of the subjects had a Y-BOCS score greater than pretreatment during the period of IPG failure. In addition, Y-BOCS scores improved back to baseline after IPG replacement in five subjects. Other symptoms potentially related to battery failure included: suicidality (n = 1), mood disturbance (n = 2), panic attacks (n = 1), fatigue (n = 2), and a restless sensation in the arms and legs (n = 1). A small number of subjects reported no side effects associated with IPG failure because of preemptive replacement (n = 2). CONCLUSIONS: This is a preliminary case series detailing the side effects resulting from IPG failure during OCD DBS. Preemptive battery replacement was an effective strategy for avoiding these issues, and timeliness in insurance reimbursement may be considered in the future. Additionally the use of rechargeable batteries may also help this issue. CLINICAL TRIAL REGISTRATION NUMBER: NCT00057603. PMID- 22305345 TI - Fundamentals of transcranial electric and magnetic stimulation dose: definition, selection, and reporting practices. AB - BACKGROUND: The growing use of transcranial electric and magnetic (EM) brain stimulation in basic research and in clinical applications necessitates a clear understanding of what constitutes the dose of EM stimulation and how it should be reported. METHODS: This paper provides fundamental definitions and principles for reporting of dose that encompass any transcranial EM brain stimulation protocol. RESULTS: The biologic effects of EM stimulation are mediated through an electromagnetic field injected (via electric stimulation) or induced (via magnetic stimulation) in the body. Therefore, transcranial EM stimulation dose ought to be defined by all parameters of the stimulation device that affect the electromagnetic field generated in the body, including the stimulation electrode or coil configuration parameters: shape, size, position, and electrical properties, as well as the electrode or coil current (or voltage) waveform parameters: pulse shape, amplitude, width, polarity, and repetition frequency; duration of and interval between bursts or trains of pulses; total number of pulses; and interval between stimulation sessions and total number of sessions. Knowledge of the electromagnetic field generated in the body may not be sufficient but is necessary to understand the biologic effects of EM stimulation. CONCLUSIONS: We believe that reporting of EM stimulation dose should be guided by the principle of reproducibility: sufficient information about the stimulation parameters should be provided so that the dose can be replicated. PMID- 22305346 TI - Left lateralizing transcranial direct current stimulation improves reading efficiency. AB - BACKGROUND: Poor reading efficiency is the most persistent problem for adults with developmental dyslexia. Previous research has demonstrated a relationship between left posterior temporal cortex (pTC) function and reading ability, regardless of dyslexia status. OBJECTIVE/HYPOTHESIS: In this study, we tested whether enhancing left lateralization of pTC using transcranial direct current stimulation (tDCS) improves reading efficiency in adults without dyslexia. METHOD: Twenty-five right-handed adults with no history of learning disorder participated. Real and sham "Left lateralizing" tDCS were applied to the pTC in separate sessions. Standardized word and nonword reading tests were given immediately after stimulation. RESULTS: Modeling of the induced electrical field confirmed that tDCS was likely to increase left pTC excitability and reduce right pTC excitability as intended. Relative to sham, real tDCS induced improvements in word reading efficiency in below average readers. CONCLUSIONS: Enhancing left lateralization of the pTC using tDCS improves word reading efficiency in below average readers. This demonstrates that left lateralization of the pTC plays a role in reading ability, and provides stimulation parameters that could be used for a trial of tDCS in adults with developmental dyslexia. Such short-term gains could amplify the effect of appropriate reading interventions when performed in conjunction with them. PMID- 22305347 TI - Haptic object matching by blind and sighted adults and children. AB - The present study describes a tactual object matching task based on the study of Lederman and Klatzky (1987) for the dimensions Exact shape, Weight, Volume and Texture. Participants were congenitally blind children and their sighted classmates, congenitally blind adults and sighted adults. To study a possible effect of familiarity the task was performed four times. Based on Millar's CAPIN (Convergent Active Processes in Interrelated Networks) model of spatial processing (Millar, 1994) it was thought that this manipulation would add redundant information to the experiment from which the children and blind participants could benefit. The results showed that accuracy was affected more by age than visual status, especially for the dimension Exact Shape. With regard to response times, children were in most cases faster than adults, especially the sighted adults. Familiarization had a significant effect on response times for all dimensions. Extra exercise only increased accuracy for the dimension Texture. These results were generally in line with the CAPIN model. PMID- 22305348 TI - Orthographic and phonological facilitation in speech production: new evidence from picture naming in Chinese. AB - Picture naming is facilitated when a target picture (e.g. of a cat) is accompanied by a form-related context word (e.g. CAP) relative to an unrelated word (e.g. PEN). Because in alphabetic languages phonological and orthographic similarity are confounded, Chinese, a logographic language, has been employed to study these two effects in isolation. The results obtained suggest that the orthographic facilitation effect is localized at an earlier processing level than the phonological facilitation effect. In the present study we examine this issue again, using an experimental design in which the context words in the related and unrelated conditions are optimally matched. In contrast to the earlier studies Experiments 1 and 2 fail to show differences in the time course of the two context effects. Moreover, Experiment 3 provides direct evidence against an early, conceptual locus of orthographic facilitation. Our findings indicate that in Chinese language production both orthographically and phonologically related context words have their effect at the rather late level of word-form encoding. PMID- 22305349 TI - Quantifying phase correction in sensorimotor synchronization: empirical comparison of three paradigms. AB - Tapping in synchrony with a metronome requires phase error correction, a process often described by a single-parameter autoregressive model. The parameter (alpha) is a measure of sensorimotor coupling strength. This study compares alpha estimates obtained from three experimental paradigms: synchronization with (1) a perfectly regular metronome (RM), (2) a perturbed metronome containing phase shifts (PS), and (3) an "adaptively timed" metronome (AT). Musically trained participants performed in each paradigm at four tempi, with baseline interval durations ranging from 400 to 1300 ms. Two estimation methods were applied to each data set. Results showed that all alpha estimates increased with interval duration. However, the PS paradigm yielded much larger alpha values than did the AT paradigm, with those from the RM paradigm falling in between. Positional analysis of the PS data revealed that alpha increased immediately following a phase shift and then decreased sharply. Unexpectedly, all PS alpha estimates were uncorrelated with the RM and AT estimates, which were strongly correlated. These results suggest that abruptly perturbed sequences engage a different mechanism of phase correction than do regular or continuously modulated sequences. PMID- 22305350 TI - Similarity-based asymmetries in perceptual matching. AB - Asymmetries, where response times differ depending on the order of two stimuli, have been widely used to explore fundamental aspects of perceptual processing. Given how much is made of asymmetries in the study of perception there has been surprisingly little research into the cognitive mechanisms that may underlie why comparing two objects in isolation depends on the order of presentation. In visual search, for example, asymmetries are typically attributed to fundamental processing characteristics as opposed to the inherent relation between two stimuli. However, one possible explanation for asymmetries found in perceptual processing is that similarity is important in the task and it is similarity itself that is asymmetric. In the current paper, we use a stimulus set for which the transformational account of similarity predicts asymmetries based on differences in transformational complexity. Using the fine-grained measure of reaction time we show that directional differences in transformation distance successfully predict asymmetries in the speed of matching two stimuli in sequence. The results are discussed in relation to the role of transformations in perceptual identification more generally, and how transformations could be revealing about how objects are compared in other experimental contexts where objects are compared directionally (e.g., visual search). PMID- 22305351 TI - Neurocognitive control in dance perception and performance. AB - Dance is a rich source of material for researchers interested in the integration of movement and cognition. The multiple aspects of embodied cognition involved in performing and perceiving dance have inspired scientists to use dance as a means for studying motor control, expertise, and action-perception links. The aim of this review is to present basic research on cognitive and neural processes implicated in the execution, expression, and observation of dance, and to bring into relief contemporary issues and open research questions. The review addresses six topics: 1) dancers' exemplary motor control, in terms of postural control, equilibrium maintenance, and stabilization; 2) how dancers' timing and on-line synchronization are influenced by attention demands and motor experience; 3) the critical roles played by sequence learning and memory; 4) how dancers make strategic use of visual and motor imagery; 5) the insights into the neural coupling between action and perception yielded through exploration of the brain architecture mediating dance observation; and 6) a neuroesthetics perspective that sheds new light on the way audiences perceive and evaluate dance expression. Current and emerging issues are presented regarding future directions that will facilitate the ongoing dialog between science and dance. PMID- 22305352 TI - Working memory load but not multitasking eliminates the prepared reflex: further evidence from the adapted flanker paradigm. AB - The prepared reflex (PR) metaphor (Exner, 1879; Woodworth, 1938) suggests that stimulus-response (S-R) instructions held in working memory (WM) can lead to autonomous response activation without any practice. Cohen-Kdoshay and Meiran (2007) showed flanker compatibility effects immediately following the instructions (First Trials Flanker Compatibility Effect, FTFCE) and also showed that FTFCE was eliminated when participants had to hold an additional novel task rule in mind. They attributed the elimination of the FTFCE to WM load, but did not rule out multitasking and associated increased control demands as a possible alternative explanation. In the present experiment, the authors compared a no load condition, a load condition involving a secondary task that was changed in every block (thus requiring WM) and a multi-tasking condition involving a secondary that remained the same throughout the experiment. The results show FTFCE without load and in the multi-tasking condition but no FTFCE in the WM load condition, establishing the critical involvement of WM storage capacity in the FTFCE. PMID- 22305353 TI - Lack of association between a functional genetic variant of connexin 37 and ischemic stroke in a Taiwanese population. AB - INTRODUCTION: Connexin 37, encoded by the GJA4 gene, protects against atherosclerosis. A recent study reported an association between polymorphism rs1764391 at GJA4 and ischemic stroke in a Chinese population. We aimed to replicate this result. MATERIALS AND METHODS: A total of 958 ischemic stroke patients and 2196 controls were enrolled for the study. All participants were Chinese residing in Taiwan. Logistic regression analysis with adjustment for traditional risk factors was used to estimate the genetic effect. We also performed stratification analyses by sex and stroke subtypes. Literature reviews were conducted for available genetic association studies investigating rs1764391 and cardiovascular phenotypes. RESULTS: We did not find any significant association for overall stroke (p=0.87) or from any subset analyses. Eight studies addressing the associations between rs1764391 and cardiovascular phenotypes had a sample size greater than 1000. Including the present study, five out of the eight large-scale studies found no association. CONCLUSIONS: GJA4 polymorphism is not associated with stroke risk in the Taiwanese population. PMID- 22305354 TI - Independent Principal Component Analysis for biologically meaningful dimension reduction of large biological data sets. AB - BACKGROUND: A key question when analyzing high throughput data is whether the information provided by the measured biological entities (gene, metabolite expression for example) is related to the experimental conditions, or, rather, to some interfering signals, such as experimental bias or artefacts. Visualization tools are therefore useful to better understand the underlying structure of the data in a 'blind' (unsupervised) way. A well-established technique to do so is Principal Component Analysis (PCA). PCA is particularly powerful if the biological question is related to the highest variance. Independent Component Analysis (ICA) has been proposed as an alternative to PCA as it optimizes an independence condition to give more meaningful components. However, neither PCA nor ICA can overcome both the high dimensionality and noisy characteristics of biological data. RESULTS: We propose Independent Principal Component Analysis (IPCA) that combines the advantages of both PCA and ICA. It uses ICA as a denoising process of the loading vectors produced by PCA to better highlight the important biological entities and reveal insightful patterns in the data. The result is a better clustering of the biological samples on graphical representations. In addition, a sparse version is proposed that performs an internal variable selection to identify biologically relevant features (sIPCA). CONCLUSIONS: On simulation studies and real data sets, we showed that IPCA offers a better visualization of the data than ICA and with a smaller number of components than PCA. Furthermore, a preliminary investigation of the list of genes selected with sIPCA demonstrate that the approach is well able to highlight relevant genes in the data with respect to the biological experiment.IPCA and sIPCA are both implemented in the R package mixomics dedicated to the analysis and exploration of high dimensional biological data sets, and on mixomics' web interface. PMID- 22305355 TI - Development of a novel microextraction by packed sorbent-based approach followed by ultrahigh pressure liquid chromatography as a powerful technique for quantification phenolic constituents of biological interest in wines. AB - A novel analytical approach, based on a miniaturized extraction technique, the microextraction by packed sorbent (MEPS), followed by ultrahigh pressure liquid chromatography (UHPLC) separation combined with a photodiode array (PDA) detection, has been developed and validated for the quantitative determination of sixteen biologically active phenolic constituents of wine. In addition to performing routine experiments to establish the validity of the assay to internationally accepted criteria (linearity, sensitivity, selectivity, precision, accuracy), experiments are included to assess the effect of the important experimental parameters on the MEPS performance such as the type of sorbent material (C2, C8, C18, SIL, and M1), number of extraction cycles (extract discard), elution volume, sample volume, and ethanol content, were studied. The optimal conditions of MEPS extraction were obtained using C8 sorbent and small sample volumes (250 MUL) in five extraction cycle and in a short time period (about 5 min for the entire sample preparation step). The wine bioactive phenolics were eluted by 250 MUL of the mixture containing 95% methanol and 5% water, and the separation was carried out on a HSS T3 analytical column (100 mm * 2.1mm, 1.8 MUm particle size) using a binary mobile phase composed of aqueous 0.1% formic acid (eluent A) and methanol (eluent B) in the gradient elution mode (10 min of total analysis). The method gave satisfactory results in terms of linearity with r(2)(-values)>0.9986 within the established concentration range. The LOD varied from 85 ng mL(-1) (ferulic acid) to 0.32 MUg mL(-1) ((+) catechin), whereas the LOQ values from 0.028 MUg mL(-1) (ferulic acid) to 1.08 MUg mL(-1) ((+)-catechin). Typical recoveries ranged between 81.1 and 99.6% for red wines and between 77.1 and 99.3% for white wines, with relative standard deviations (RSD) no larger than 10%. The extraction yields of the MEPS(C8)/UHPLC PDA methodology were found between 78.1 (syringic acid) and 99.6% (o-coumaric acid) for red wines and between 76.2 and 99.1% for white wines. The inter-day precision, expressed as the relative standard deviation (RSD%), varied between 0.2% (p-coumaric and o-coumaric acids) and 7.5% (gentisic acid) while the intra day precision between 0.2% (o-coumaric and cinnamic acids) and 4.7% (gallic acid and (-)-epicatechin). On the basis of analytical validation, it is shown that the MEPS(C8)/UHPLC-PDA methodology proves to be an improved, reliable, and ultra-fast approach for wine bioactive phenolics analysis, because of its capability for determining simultaneously in a single chromatographic run several bioactive metabolites with high sensitivity, selectivity and resolving power within only 10 min. Preliminary studies have been carried out on 34 real whole wine samples, in order to assess the performance of the described procedure. The new approach offers decreased sample preparation and analysis time, and moreover is cheaper, more environmentally friendly and easier to perform as compared to traditional methodologies. PMID- 22305356 TI - Analysis of volatile bases by high performance liquid chromatography with aerosol based detection. AB - The development and performance of two methods are described whereby low levels of volatile bases are quantified by HPLC using either a charged aerosol detector (CAD) or a nano-quantity analyte detector (NQAD). A test set of 12 volatile bases (ammonia, hydrazine, methylamine, ethylamine, diethylamine, triethylamine, isobutylamine, N,N-diisopropylethylamine, morpholine, piperazine, ethylenediamine, and 1,4-diazabicyclo[2.2.2]octane) were analyzed. The studied compounds all exhibit poor UV chromophores and are typically undetectable by aerosol-based detection when using conventional volatile mobile phases. The ability to detect these analytes by CAD or NQAD depended on their propensity towards formation of a low volatility salt between the target analyte and mobile phase modifier. Trifluoroacetic acid (TFA) was found to significantly improve detection of most volatile bases. A low concentration (0.2 mM) of hydrochloric acid was additionally needed to enable detection of ammonia. The compounds were separated under hydrophilic interaction liquid chromatography (HILIC) conditions on a zic-pHILIC column. For all analytes, limits of detection (LOD) were measured in the range of 1-27 ng on column, which is comparable to previously reported detection limits for non-volatile analytes. PMID- 22305357 TI - Recent advances in flow-controlled multidimensional gas chromatography. AB - The continued development of flow-controlled two-dimensional gas chromatography (2-D GC) is reviewed, with a special emphasis on results published from 2001 through 2011. Heart-cutting 2-D GC continues to be used for isolating selected components in complex mixtures. The programmable and highly precise flows and temperatures produced by modern gas chromatographs have made it easier to selectively transfer analytes to the secondary column and to backflush unwanted components from the primary column. Several new Deans switch interfaces for performing heart-cutting 2-D GC have been introduced, with most attention given to devices that integrate the flow connections into a single unit. Heart-cutting 2-D GC has been used to isolate analytes in a wide variety of complex mixtures including fuels, industrial feedstocks, fragrances, and environmental extracts. Valve-based comprehensive 2-D GC (GC*GC) was also actively developed in the past decade. Valve-based modulation is a simple way to generate GC*GC separations without using cryogenic fluids. More than ten new valve-based modulators were introduced. Diaphragm valves fitted with sample loops are the most common low duty cycle modulators, whereas fluidic modulators that employ differential flow conditions are the most common high duty cycle modulators. Applications of valve based GC*GC include analysis of hydrocarbon mixtures, essential oils, and environmental samples. PMID- 22305358 TI - Chromatographic retention behaviour of monosubstituted benzene derivatives on porous graphitic carbon and octadecyl-bonded silica studied using molecular modelling and quantitative structure-retention relationships. AB - The retention behaviour of a series of 28 monosubstituted benzenes, representing a diverse range of functional groups and substituent shape, were investigated using porous graphitic carbon (PGC) and octadecyl-bonded silica (ODS) stationary phases. For the majority of analytes retention on PGC was greater than on ODS, and in most cases this effect occurred at both pH 2.5 and 7.0. The main trends observed on PGC (in comparison with ODS) were: (i) similar or reduced retention of low polarity molecules such as the hydrocarbon and halogenated analytes; (ii) increased retention of conjugated analytes with extended planarity; (iii) increased retention of polar and charged species; and (iv) substantial increases in retention for selected polar and negatively charged analytes, including some ionised and unionised acid analytes. Poor retention of positively charged analytes was observed on both stationary phases. Molecular modelling studies have explored the geometry of pi-pi stacking interactions in retention on PGC and have highlighted the strong retention of large conjugated analytes, with extended planar conformations, which can interact with the graphite surface with cofacial geometry. Quantitative structure-retention relationships showed the importance of hydrophobic (pi) and electronic factors (e.g. mean polarisability and LUMO energy) in retention on PGC, whilst retention on ODS was correlated to hydrophobicity (logP and pi). PMID- 22305359 TI - Screening strategies for achiral supercritical fluid chromatography employing hydrophilic interaction liquid chromatography-like parameters. AB - A thorough evaluation of 5 MUm bare silica from two major vendors for achiral supercritical fluid chromatography of polar analytes has been carried out. Columns were the same dimension, and a virgin column was reserved for each modifier-mixture combination. Three mixtures were prepared and chromatographically separated via a gradient of methanol-modified CO(2) that incorporated 5% (w/w) water as a neutral additive. Mixture (A) invoked both trifluoroacetic acid and water as additives. Mixture (B) utilized isopropyl amine and water; while mixture (C) employed either ammonium acetate and water as additives or only water. Regardless of the mixture components and mobile phase composition, duplicate separations with superior selectivity and excellent peak resolution were observed on five analysis days over a 15-day period. Subsequent removal of water (i.e. primary additive) from each of the mobile phases led to lower selectivity for early eluting components but excellent peak resolution prevailed for later eluting peaks during a later 5-day testing period with only the secondary additive. The re-introduction of 5% water into the mobile phase (after allowing the bare silica columns that were used with no water to sit for 30 days) slowly yielded the original separation after approximately five injections. A hydrophilic interaction liquid chromatography (HILIC)-like mechanism for SFC whereby analyte partitions between water absorbed on the silica and water in the mobile phase is proposed. The general utility of this experimental approach with bare silica was subsequently demonstrated by single injection of ten drug-like compounds with each of the four mobile phases that previously were utilized with the three model compound mixtures. In each case, sharp peaks were observed for each drug-like compound regardless of the additive although retention times varied with the additive employed. PMID- 22305360 TI - Quantification of nerve agent adducts with albumin in rat plasma using liquid chromatography-isotope dilution tandem mass spectrometry. AB - A sensitive method for the determination of the organophosphorus nerve agents sarin, soman and VX adducts with tyrosine residue of albumin in rat plasma has been developed and validated using liquid chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS). O-(O-Alkyl methylphosphonyl) tyrosine adducts and their deuterated products that were used as the internal standards were synthesised to establish the quantitative isotope-dilution method. Protein purification and solid-phase extraction (SPE) were applied to improve the recovery efficiency, reduce interference and achieve high sensitivity. The method provided a detection limit of 0.01 ng/mL for sarin and soman adducts and 0.05 ng/mL for the VX adduct. The value of the intra-day relative standard deviation over the calibration range was less than 6.16% (n=6), and that of the inter-day was less than 12.7% (n=6). The recovery varied from 86% to 111%. This sensitive method was successfully applied to the analysis of adducts in rat plasma after nerve agent exposure, and the results demonstrated the dose-effect relationships. PMID- 22305361 TI - Determination of phenols with ion chromatography-online electrochemical derivatization based on porous electrode-fluorescence detection. AB - The current study describes the determination of phenols using ion chromatography online electrochemical derivatization-fluorescence detection (IC/ED/FD). Six model phenols including 4-methylphenol (pMP), 2, 4-dimethylphenol (DMP), 4-tert butylphenol (TBP), 4-hydroxylphenolacetic acid (pHPA), 4-acetamidophenol (pAAP), and phenol (P) were well separated on an anion-exchange column under ion exchange mode using NaOH with small amount of acetonitrile added as eluent. Online electrochemical derivatization performed via a laboratory-made electrolytic cell (EC), consisting of porous titanium electrode and cation-exchange membrane (CEM), allows the oxidation products that are strongly fluorescent to be detected by the fluorescence detector. NaOH eluent used in the present method matches well with the maximal fluorescence intensity obtained at alkaline condition for oxidized phenols, thus the addition of specific buffer solution after oxidation encountered in previous report could be eliminated. This process leads to a simplified procedure. The proposed method was sensitive to the limits of detection in the range of 0.4 MUg/L and 3.8 MUg/L and the limits of quantification between 1.2 MUg/L and 13 MUg/L due to the strong electro-oxidation capacity of porous titanium electrode, as well as the implementation of time programmed potential over EC. The linear ranges were 2.0-1.0 * 10(4) MUg/L for pAAP and DMP, and 10-1.0 * 10(4) MUg/L for P, pMP, pHPA, and TBP, respectively. The relative standard deviations range from 0.9% to 4.8%. The utilization of the method was demonstrated by the analysis of real samples. The average spiked recoveries of target analytes in pool water were 81.0-118%. PMID- 22305362 TI - Quantitative high-performance liquid chromatography-tandem mass spectrometry impurity profiling methods for the analysis of parenteral infusion solutions for amino acid supplementation containing L-alanyl-L-glutamine. AB - Potential impurities in a parenteral infusion solution for amino acid supplementation containing alanylglutamine (AlaGln) and glycyltyrosine (GlyTyr) as peptide constituents have been determined. Such complex multicomponent pharmaceutical formulations with reactive ingredients may yield a multitude of impurities in stress testing samples. Thus, three stability indicating LC-ESI MS/MS methods were developed for the establishment of quantitative impurity profiles employing a Chiralpak QN-AX and a Polysulfoethyl A stationary phase in HILIC mode as well as a Gemini C18 stationary phase in gradient RPLC mode. The primary goal was to separate isobaric compounds (stereoisomers, constitutional isomers, retro-peptides) and to provide quantitative data of impurities identified in stressed nutritional infusion solutions. The optimized methods were calibrated by standard addition in the samples and validated according to ICH guidelines. The methods were then applied for the analysis of stressed sample solutions stored under different conditions. Major peptide impurities found in concentrations above the qualification threshold in stressed solutions stored at 40 degrees C for 6 months comprised cyclo(AlaGln) 808 MUg/mL, pyroGluAla 122 MUg/mL, AlaGlu 117 MUg/mL, cycloGlyTyr 60 MUg/mL, AlaGln epimers (DL+LD) 38 MUg/mL, and TyrGly 27 MUg/mL. A number of impurities above the reporting threshold were also detected including AlaAlaGln 18 MUg/mL, cyclo(AlaGlu) 16 MUg/mL, AlaGlu(AlaGln) 17 MUg/mL, and AlaGlu(His) 12 MUg/mL. The study showed that bioactive peptides may be formed in amino acid infusion solutions by condensation of amino acids and a careful control of these impurities is mandatory. PMID- 22305363 TI - Application of vesicular coacervate phase for microextraction based on solidification of floating drop. AB - A new, efficient and environmentally friendly method for the analysis of parabens as model compounds was developed using solidified floating vesicular coacervative drop microextraction (SFVCDME). A supramolecular solvent consisting of vesicles of decanoic acid in the nano- and microscale regimes was firstly used as the solvent in solidification of floating drop microextraction. The solvent was produced from the coacervation of decanoic acid aqueous vesicles in the presence of tetrabutylammonium (Bu(4)N(+)). Methylparaben (MP), ethylparaben (EP), and propylparaben (PP) were extracted on the basis of hydrophobic and pi-cation interactions and the formation of hydrogen bonds. Microliter volume of vesicular coacervative droplet was delivered to the surface of the aqueous sample, and the sample was stirred for a desired time. The sample vial was cooled by immersing it into an ice bath for 3 min. The solidified solvent was transferred into a suitable vial and melted immediately. Twenty microliter of the vesicular coacervative solvent was directly injected to high-performance liquid chromatography-ultraviolet detection, with no need to dilution or solvent evaporation. Several parameters affecting the microextraction efficiency including sample temperature, stirring rate, pH, salt effect, volume of the solvent and extraction time were investigated and optimized. Under optimum conditions, preconcentration factors and relative recoveries of the studied compounds were obtained in the range of 81-174 and 91-108%, respectively; and the performance of the method was comparable with that of solid-phase extraction as the reference method. PMID- 22305364 TI - Identification of bioactive peptides in a functional yogurt by micro liquid chromatography time-of-flight mass spectrometry assisted by retention time prediction. AB - In this study we used micro liquid chromatography coupled to time-of-flight mass spectrometry (microLC-TOF-MS) for separation and identification of bioactive peptides in a yogurt marketed as an antihypertensive functional food. An appropriate sample clean-up using solid-phase extraction (SPE) allowed detection of a large number of low-molecular-mass bioactive peptides by reversed-phase microLC-TOF-MS. The preliminary identification was solely based on the experimental monoisotopic molecular mass values (M(exp)). Later, we evaluated the correlations between predicted normalized elution time (NET) and experimental normalized retention times (t(r)') values to describe the retention behavior of the proposed sequences. The assistance of retention prediction proved to be useful to improve reliability of the identification, avoiding misinterpretations and solving some identity conflicts. After revision, the identity of only fifty bioactive peptides was confirmed. Significant number of these peptides was reported as angiotensin converting enzyme (ACE) inhibitors and nine of them were antihypertensive. The presence of peptide sequences with other biological activities such as antibacterial, antithrombotic, antioxidant, cell modulation, immune or phagocytosis stimulation, epitopes of B cells and opioid agonists was also confirmed. PMID- 22305365 TI - Performance optimizing injection sequence for minimizing injection band broadening contributions in high efficiency liquid chromatographic separations. AB - The observed performance when using high efficiency, low volume (U)HPLC columns has and continues to be limited by the extra column dispersion introduced by the chromatographic system. Even with the latest UHPLC instruments the injection and detection systems are still major contributors to peak broadening, especially when using 50 mm * 2.1mm columns. A previously described injection technique now termed Performance Optimizing Injection Sequence (POISe) was shown to reduce or eliminate the impact of the injection system on the observed chromatographic performance. The POISe technique involves injecting a defined volume of weak solvent along with the sample in order to increase retention factors during sample loading. In the present study, a newly developed equation describing the phenomena involved during sample introduction is presented and shows that analyte bands are compressed at the head of the column in proportion to their retention factor independent of the elution mode (i.e. gradient or isocratic). This phenomenon is termed isocratic focusing and is shown to be most effective with analytes having retention factors in the range of 0.4-3. Additionally, it is shown that gradient compression plays a minor role in band compression when using this technique with analytes having retention factors of 1 or higher. The POISe technique is further investigated experimentally to determine its optimum configuration. It is also demonstrated to be effective with different HPLC and UHPLC instrument platforms and different high efficiency columns, such as those packed sub-2 MUm and core-shell particles. PMID- 22305366 TI - The New York PTSD risk score predicts having, not developing, PTSD. PMID- 22305367 TI - Valproate-induced hyperammonemic encephalopathy: an update on risk factors, clinical correlates and management. AB - INTRODUCTION: Valproate (VPA)-induced hyperammonemic encephalopathy (VHE) is a serious drug-related adverse effect characterized by lethargy, vomiting, cognitive slowing, focal neurological deficits and decreased levels of consciousness ranging from drowsiness to coma. METHODS: We present a case series (n=5) and also review previous cases of VHE (n=30) in psychiatric patients to provide an update on risk factors, clinical correlates and management of VHE. RESULTS: To our knowledge, there are 30 (16 female, 14 male) previously reported VHE cases in psychiatric patients. Risk factors for VHE include VPA-drug interactions, mental retardation, carnitine deficiency and presence of urea cycle disorders. Length of VPA treatment, VPA dosage, serum VPA levels and serum ammonia levels do not appear to correlate with onset or severity of VHE.VPA discontinuation is the primary treatment of VHE, although, l-carnitine, lactulose and neomycin have been used adjunctively in some patients. CONCLUSION: Clinicians should consider VHE in patients taking VPA who present with lethargy, gastrointestinal symptoms, confusion and decreased levels of drowsiness. VPA discontinuation is currently the mainstay of treatment for VHE, although more research is warranted to delineate the underlying risk factors for VHE and consolidate treatment modalities for this potentially life-threatening drug adverse effect. PMID- 22305368 TI - A case of 'cybersuicide' attempt using chloroform. PMID- 22305369 TI - Cardiovascular risk factors in patients with first-episode psychosis in Sao Paulo, Brazil. AB - OBJECTIVE: The objective was to evaluate the cardiovascular profile of first episode psychosis patients in Sao Paulo, Brazil, an issue that has not been sufficiently explored in low-/middle-income countries. METHOD: A cross-sectional study was performed 1 to 3 years after an initial, larger survey that assessed first-episode psychosis in Sao Paulo. We evaluated cardiovascular risk factors and lifestyle habits using standard clinical examination and laboratory evaluation. RESULTS: Of 151 contacted patients, 82 agreed to participate (mean age=35 years; 54% female). The following diagnoses were found: 20.7% were obese, 29.3% had hypertension, 39.0% had dyslipidemia, 19.5% had metabolic syndrome, and 1.2% had a >20% 10-year risk of coronary heart disease based on Framingham score. Also, 72% were sedentary, 25.6% were current smokers, and 7.3% reported a heavy alcohol intake. CONCLUSION: Compared to other samples, ours presented a distinct profile of higher rates of hypertension and diabetes (possibly due to dietary habits) and lower rates of smoking and alcohol intake (possibly due to higher dependence on social support). Indirect comparison vs. healthy, age-matched Brazilians revealed that our sample had higher frequencies of hypertension, diabetes and metabolic syndrome. Therefore, we confirmed a high cardiovascular risk in first-episode psychosis in Brazil. Transcultural studies are needed to investigate to which extent lifestyle contributes to such increased risk. PMID- 22305370 TI - Psychological comorbidities in Chinese patients with acute-on-chronic liver failure. AB - OBJECTIVES: Patients with acute-on-chronic liver failure (ACLF) experience long term chronic liver diseases plus an acute liver function decompensation. This study aimed to determine whether psychological symptoms in patients with hepatitis B virus (HBV)-related ACLF differ from those with other chronic liver diseases and to identify which factors could predict psychological impairment in liver patients. METHODS: This was a paired case-control study. A total of 120 inpatients, including 40 cases for HBV-related ACLF, 40 paired controls for HBV related cirrhosis and 40 paired controls for chronic hepatitis B (CHB), as well as 40 paired healthy controls were studied. RESULTS: A high proportion of patients with HBV-related ACLF were classified as Child's stage C. The prevalence of depression in patients with HBV-related ACLF was significantly higher than in CHB patients and healthy controls, but was equivalent to patients with HBV related cirrhosis. Patients with HBV-related ACLF had significantly higher level of self-esteem than those with HBV-related cirrhosis. However, there was no significant difference among the three liver patient groups and healthy controls in anxiety and suicide intent. Lower education level, anxiety, poor sleep quality and greater severity of disease were associated with elevated depression. CONCLUSIONS: Patients with HBV-related ACLF and cirrhosis are at higher risk of depression. It appears that severity of liver disease measured by Child-Pugh class, rather than additional acute liver function decompensation, significantly predicted depression among liver patients. PMID- 22305371 TI - Chondroitin sulfates in the developing rat hindbrain confine commissural projections of vestibular nuclear neurons. AB - BACKGROUND: Establishing correct neuronal circuitry is crucial to proper function of the vertebrate nervous system. The abundance of chondroitin sulfate (CS) proteoglycans in embryonic neural environments suggests that matrix proteoglycans regulate axonal projections when fiber tracts have not yet formed. Among the early-born neurons, the vestibular nucleus (VN) neurons initiate commissural projections soon after generation at E12.5 and reach the contralateral target by E15.5 in the rat hindbrain. We therefore exploited 24-hour cultures (1 day in vitro (DIV)) of the rat embryos and chondroitinase ABC treatment of the hindbrain matrix to reveal the role of CS moieties in axonal initiation and projection in the early hindbrain. RESULTS: DiI tracing from the VN at E12.5(+1 DIV) showed contralaterally projecting fibers assuming fascicles that hardly reached the midline in the controls. In the enzyme-treated embryos, the majority of fibers were unfasciculated as they crossed the midline at 90 degrees . At E13.5(+1 DIV), the commissural projections formed fascicles and crossed the midline in the controls. Enzyme treatment apparently did not affect the pioneer axons that had advanced as thick fascicles normal to the midline and beyond, towards the contralateral VN. Later projections, however, traversed the enzyme-treated matrix as unfasciculated fibers, deviated from the normal course crossing the midline at various angles and extending beyond the contralateral VN. This suggests that CSs also limit the course of the later projections, which otherwise would be attracted to alternative targets. CONCLUSIONS: CS moieties in the early hindbrain therefore control the course and fasciculation of axonal projections and the timing of axonal arrival at the target. PMID- 22305372 TI - [Pyothorax-associated lymphoma]. PMID- 22305373 TI - Soluble factors from multipotent mesenchymal stromal cells have antinecrotic effect on cardiomyocytes in vitro and improve cardiac function in infarcted rat hearts. AB - The mechanisms underlying the functional improvement after injection of multipotent mesenchymal stromal cells (MSCs) in infarcted hearts remain incompletely understood. The aim of this study was to investigate if soluble factors secreted by MSCs promote cardioprotection. For this purpose, conditioned medium (CM) was obtained after three passages from MSC cultures submitted to 72 h of conditioning in serum-free DMEM under normoxia (NCM) or hypoxia (HCM) conditions. CM was concentrated 25-fold before use (NCM-25X, concentrated normoxia conditioned medium; HCM-25X, concentrated hypoxia conditioned medium). The in vitro cardioprotection was evaluated in neonatal ventricular cardiomyocytes by quantifying apoptosis after 24 h of serum deprivation associated with hypoxia (1% O(2)) in the absence or presence of NCM and HCM (nonconcentrated and 25-fold concentrated). The in vivo cardioprotection of HCM was tested in a model of myocardial infarction (MI) induced in Wistar male rats by permanent left coronary occlusion. Intramyocardial injection of HCM-25X (n = 14) or nonconditioned DMEM (n = 16) was performed 3 h after coronary occlusion and cardiac function was evaluated 19-21 days after medium injection. Cardiac function was evaluated by electro- and echocardiogram, left ventricular catheterization, and treadmill test. The in vitro results showed that HCM was able to decrease cardiomyocyte necrosis. The in vivo results showed that HCM-25X administered 3 h after AMI was able to promote a significant reduction (35%) in left ventricular end-diastolic pressure and improvement of cardiac contractility (15%) and relaxation (12%). These results suggest that soluble factors released in vitro by MSCs are able to promote cardioprotection in vitro and improve cardiac function in vivo. PMID- 22305374 TI - Starmerella bombicola influences the metabolism of Saccharomyces cerevisiae at pyruvate decarboxylase and alcohol dehydrogenase level during mixed wine fermentation. AB - BACKGROUND: The use of a multistarter fermentation process with Saccharomyces cerevisiae and non-Saccharomyces wine yeasts has been proposed to simulate natural must fermentation and to confer greater complexity and specificity to wine. In this context, the combined use of S. cerevisiae and immobilized Starmerella bombicola cells (formerly Candida stellata) was assayed to enhance glycerol concentration, reduce ethanol content and to improve the analytical composition of wine. In order to investigate yeast metabolic interaction during controlled mixed fermentation and to evaluate the influence of S. bombicola on S. cerevisiae, the gene expression and enzymatic activity of two key enzymes of the alcoholic fermentation pathway such as pyruvate decarboxylase (Pdc1) and alcohol dehydrogenase (Adh1) were studied. RESULTS: The presence of S. bombicola immobilized cells in a mixed fermentation trial confirmed an increase in fermentation rate, a combined consumption of glucose and fructose, an increase in glycerol and a reduction in the production of ethanol as well as a modification in the fermentation of by products. The alcoholic fermentation of S. cerevisiae was also influenced by S. bombicola immobilized cells. Indeed, Pdc1 activity in mixed fermentation was lower than that exhibited in pure culture while Adh1 activity showed an opposite behavior. The expression of both PDC1 and ADH1 genes was highly induced at the initial phase of fermentation. The expression level of PDC1 at the end of fermentation was much higher in pure culture while ADH1 level was similar in both pure and mixed fermentations. CONCLUSION: In mixed fermentation, S. bombicola immobilized cells greatly affected the fermentation behavior of S. cerevisiae and the analytical composition of wine. The influence of S. bombicola on S. cerevisiae was not limited to a simple additive contribution. Indeed, its presence caused metabolic modifications during S. cerevisiae fermentation causing variation in the gene expression and enzymatic activity of alcohol deydrogenase and pyruvate decarboxilase. PMID- 22305375 TI - The dawn of the ISHLT Mechanical Assisted Circulatory Support (IMACS) Registry: fulfilling our mission. PMID- 22305376 TI - The Fourth INTERMACS Annual Report: 4,000 implants and counting. AB - The Fourth Annual Report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes and analyzes the first 5 years of patient and data collection. With more than 4,000 patients entered into the database, the evolution of pump technology, strategy at implant, and pre-implant patient profiles are chronicled. A risk factor analysis of the entire adult primary implant population is provided, and the recent composition of patient profiles is examined. Current actuarial survival with continuous-flow pumps exceeds 80% at 1 year and 70% at 2 years. PMID- 22305377 TI - Evaluation of valganciclovir pharmacokinetics in lung transplant recipients. AB - BACKGROUND: Valganciclovir is commonly used for cytomegalovirus prevention after lung transplantation. The pharmacokinetic profile of valganciclovir in lung transplant patients has not been well described or linked to efficacy and safety. METHODS: This prospective, randomized, crossover study determined the steady state pharmacokinetic profile of 2 different doses of valganciclovir in lung transplant recipients and compared these profiles with intravenous ganciclovir. RESULTS: Ten patients were evaluated. Patients were 56.8 +/- 3.4 years old and had a mean creatinine clearance of 69 +/- 9 ml/min. Oral bioavailability of ganciclovir after administration of valganciclovir was 59%, and mean half-life was 3.73 +/- 1.15 hours. The maximal concentration after intravenous 5 mg/kg ganciclovir was significantly higher than after 450 mg valganciclovir (8.37 +/- 3.03 mg/liter vs. 5.3 +/- 2.09 mg/liter, respectively; p = 0.02) and similar to 900 mg valganciclovir (7.93 +/- 3.97 mg/liter; p = 0.78). A higher area under the curve at 0-24 hours (AUC(0-24)) was found with 900 mg valganciclovir compared with intravenous 5 mg/kg/day ganciclovir (47.8 +/- 19.7 vs 32.9 +/- 10.8 mg . hour/liter, respectively; p = 0.049). The AUC(0-24) for 450 mg valganciclovir twice daily was 45.5 +/- 22.9 mg . hour/liter. CONCLUSION: Valganciclovir at 900 mg/day resulted in the equivalent of a mean daily dose of 7.7 mg/kg intravenous ganciclovir. Higher systemic ganciclovir exposures occurred after 900 mg/day valganciclovir compared with intravenous 5 mg/kg/day ganciclovir. Valganciclovir therapeutic drug monitoring may be warranted in select lung transplant patients to avoid increased toxicity. PMID- 22305378 TI - Extremes of body mass index do not impact mid-term survival after continuous-flow left ventricular assist device implantation. AB - BACKGROUND: Extremes of body mass index (BMI) are often considered contraindications to use of a left ventricular assist device (LVAD), but data regarding outcomes across the spectrum of BMI are limited. We sought to assess the association of BMI with survival and major morbidity after continuous-flow (CF) LVAD implantation. METHODS: Patients (n = 896) enrolled in the HeartMate II LVAD bridge-to-transplantation and destination therapy trials were divided into 4 BMI groups: underweight (<18.5 kg/m(2)); normal (18.5 kg/m(2) <= BMI < 30 kg/m(2)); obese (30 kg/m(2) <= BMI < 35 kg/m(2)); and extremely obese (>=35 kg/m(2)). The association of BMI with survival was tested using Kaplan-Meier analysis and proportional hazards regression. Major adverse events were compared using Poisson's regression and chi-square tests. RESULTS: At implantation, 48 (5%) patients were underweight, 596 (67%) normal weight, 164 (18%) obese and 88 (10%) extremely obese. BMI extremes were associated with differences in creatinine, albumin, age, central venous pressure and etiology. BMI was not associated with survival in the univariate analysis (p = 0.83) or in adjusted models (extremely obese: hazard ratio [HR] 1.29, p = 0.231; obese: HR 0.94, p = 0.723; underweight: HR 1.23, p = 0.452). Underweight patients were more likely to have bleeding events (p < 0.001), whereas extremely obese patients had higher rates of device-related infection (p = 0.041) and rehospitalization (p = 0.014). CONCLUSIONS: Overall survival in patients receiving CF LVAD is similar across BMI categories. Carefully selected patients at both extremes of BMI have good mid term survival after LVAD and should be considered for LVAD implantation relative to overall risk profile. PMID- 22305379 TI - ABO-incompatible heart transplantation: analysis of the Pediatric Heart Transplant Study (PHTS) database. AB - BACKGROUND: ABO incompatible (ABOi) heart transplantation is an accepted approach to increasing organ availability for young patients. Previous studies have suggested that early survival for ABOi transplants is similar to ABO compatible (ABOc) transplants. We analyzed the Pediatric Heart Transplant Study (PHTS) database from 1/96 to 12/08 to further assess this strategy. METHODS: We analyzed the numbers of ABOi and ABOc done at the PHTS centers. We then compared the clinical characteristics, and short-term freedom from death, rejection and infection in the ABOi patients with the patients that had an ABOc heart transplant during the same period. All patients were less than or equal to 15 months of age at listing (the age of the oldest ABOi patient). We adjusted for co variates shown to increase risk for mortality (age less than 1 month, extracorporeal membrane oxygenation (ECMO), ventilator, previous sternotomy, and congenital heart disease). RESULTS: There were 931 total transplants done at 34 PHTS centers during the 12 year time period in patients <=15 months of age. Of these, 502 transplants were performed at 20 PHTS centers that did at least one ABOi heart transplant. Eighty-five of the 502 (17%) were ABOi. At time of transplant, ABOi recipients compared with ABOc were more likely to be on a ventilator (49.4% vs 36.5%, p=0.025), and more often supported with ECMO (23.5% vs 13.4%, p=0.018). There was similar survival at 12 months (82% vs 84%, p=0.7). In risk adjusted analysis ABOi status was not associated with 1 year mortality (HR 0.85, 95% CI 0.45-1.6, p=0.61). The ABOi patients had greater freedom from rejection when compared with ABOc patients for all 34 centers (75% vs 62%, p=0.016), but the difference was not significant when limited only to the 20 centers doing ABOi transplants (75% vs 69%, p=0.4). The ABOi cohort had lower infection rates (23.5% vs 37.9%, p = 0.013). This difference remained after adjusting for center and other covariates. CONCLUSIONS: In center and risk adjusted analysis, young children who received an ABOi transplant had equivalent one-year survival and freedom from rejection compared with those who received an ABOc transplant. In spite of the favorable outcome for ABOi recipients, many centers appear to reserve ABOi transplantation for sicker patients. These data mandate reexamination of the current United Network for Organ Sharing (UNOS) policy that gives priority to ABOc over ABOi transplantation in the United States. PMID- 22305380 TI - Peripartum cardiomyopathy: post-transplant outcomes from the United Network for Organ Sharing Database. AB - BACKGROUND: Nearly 25% of patients with peripartum cardiomyopathy (PPCM) will require cardiac transplantation. Whether post-transplant outcomes differ among patients with PPCM compared with other recipients remains unsettled. METHODS: The United Network for Organ Sharing database was queried for cardiac transplants, comparing characteristics and outcomes for PPCM, other women, and all others. RESULTS: Between 1987 and 2010, 42,406 patients (9,419 women and 32,987 men) received a heart transplant. Of these, 485 women who had PPCM as the indication were younger (p < 0.001), had higher sensitization (p < 0.001), required higher intensity of cardiovascular support pre-transplant (p = 0.026), and had higher listing status (p < 0.001). Those with PPCM had more post-transplant rejection during the index transplant hospitalization (p < 0.001) and during the first year (p = 0.003). Comparing PPCM with other women and all others, graft survival was inferior (p = 0.004 and p < 0.003, respectively) and age-adjusted survival was lower (p < 0.001 and p = 0.02, respectively). CONCLUSIONS: This large report shows outcomes of graft failure and death are inferior for recipients with PPCM, which may be partly explained by younger age, higher allosensitization, higher pre-transplant acuity, and increased rejection. More research is needed to determine management strategies to improve outcomes in PPCM heart transplant recipients. PMID- 22305381 TI - Reconditioning of lungs donated after circulatory death with normothermic ex vivo lung perfusion. AB - BACKGROUND: The use of donation-after-circulatory-death (DCD) donors for lung transplantation has come into practice. In this study we investigated whether DCD lungs can be resuscitated after warm ischemia with normothermic ex vivo lung perfusion (EVLP). METHODS: Four hours after cardiac arrest, beagle dogs were divided into two groups (n = 6 each): those with static cold storage (SCS group) and those with normothermic EVLP (EVLP group), for 3.5 hours. Physiologic lung functions were evaluated during EVLP. In both groups, the left lungs were then transplanted and reperfused for 4 hours to evaluate post-transplant lung functions. Lung tissue adenosine triphosphate (ATP) levels were measured at given time-points. RESULTS: Lung oxygenation was significantly improved with EVLP (p < 0.01), and lung oxygenation at the end of EVLP significantly reflected post transplant lung oxygenation (r = 0.99, p < 0.01). Post-transplant lung oxygenation was significantly better in the EVLP group than in the SCS group (p < 0.05). Both dynamic pulmonary compliance and wet-to-dry lung weight ratio 4 hours after transplantation were also significantly better in the EVLP group than in the SCS group (p < 0.05). Microthrombi in the donor lungs before transplantation were microscopically detected more often in the SCS group. The lung tissue ATP levels 4 hours after transplantation were significantly higher in the EVLP group compared with the SCS group (p = 0.03). CONCLUSIONS: Normothermic ex vivo lung perfusion could resuscitate DCD lungs injured by warm ischemia, and may ameliorate ischemia-reperfusion injury. PMID- 22305382 TI - Effect of simvastatin on development of obliterative airway disease: an experimental study. AB - BACKGROUND: Obliterative bronchiolitis after lung transplantation is characterized by airway inflammation leading to obliteration of small airways. Statins are known to have lipid-independent immunomodulatory properties. We investigated the effect of simvastatin treatment on innate and adaptive immune responses and the development of obliterative airway disease (OAD). METHODS: In fully MHC-mismatched rat tracheal allograft recipients, we used simvastatin at different doses (0.1 to 20 mg/kg/day orally) to assess its effect on OAD development. No immunosuppressive treatment was administered. Histologic, immunohistochemical and real-time RT-PCR analyses were performed 3, 10 and 30 days after transplantation. RESULTS: Simvastatin treatment with doses ranging from 0.5 to 20 mg/kg/day significantly enhanced early epithelial recovery and reduced the development of OAD. No dose response was observed. Simvastatin treatment markedly reduced IL-23 mRNA and lymphocyte chemokine CCL20 production, and the infiltration of CD4(+) and CD8(+) T cells into allografts already at 3 days. At 10 days, simvastatin significantly attenuated the production of pro inflammatory cytokines, IL-1beta, TNF-alpha, MCP-1 and IP-10, and Th17-polarizing cytokines, IL-6 and IL-17e, and inhibited allograft infiltration by inflammatory cells. The protective effects of simvastatin on inflammation and OAD were partially mediated through nitric oxide synthase. CONCLUSIONS: Simvastatin treatment inhibited adaptive T-cell alloimmune activation as depicted by reduced expression of lymphocyte chemokine and pro-inflammatory cytokine mRNA and reduced allograft infiltration by inflammatory cells. Importantly, simvastatin inhibits the development of OAD and this effect is partially mediated by increased nitric oxide activity. These results suggest a role for simvastatin in the prevention of obliterative bronchiolitis. PMID- 22305383 TI - Construction of vascularized cardiac tissue from genetically modified mouse embryonic stem cells. AB - BACKGROUND: The aim of myocardial tissue engineering is to repair or regenerate damaged myocardium with engineered cardiac tissue constructed by a combination of cells and scaffolds in vitro. However, this strategy has been hampered by the lack of cardiomyocytes and the significant cell death after transplantation in vivo. METHODS: In this study we explored the feasibility of in vitro construction of vascularized cardiac muscle using genetically modified mouse embryonic stem cells (ESCs) transfected by pMHC-neo/SV40-hygro. A stirred bioreactor was used to facilitate the formation of a large number of ESC-derived cardiomyocytes, which were then mixed with human umbilical vein endothelial cells (HUVECs) and mouse embryonic fibroblasts (MEFs) in a liquid collagen scaffold to construct highly vascularized cardiac tissue in vitro. RESULTS: The resulting tissue constructs were transplanted into dorsal subcutaneous sites of nude mice. Tumor formation was not detected in all samples and vascularized cardiac tissue could survive after transplantation. Vascularization of the implanted cardiac muscle was significantly enhanced by the addition of HUVECs and MEFs, which resulted in a thicker myocardium. The combination of genetically modified ESCs and stirred bioreactor cultivation not only benefited the large-scale production of pure ESC derived cardiomyocytes, but also effectively controlled the potential risk of undifferentiated ESCs. CONCLUSIONS: Using liquid collagen as scaffold, the enriched cardiomyocytes derived from genetically modified ESCs mixed with HUVECs and MEFs in 3-dimensional culture resulted in highly vascularized cardiac tissues. PMID- 22305384 TI - Searching for novel molecular targets of chronic rejection in an orthotopic experimental lung transplantation model. AB - BACKGROUND: Chronic rejection (CR) is the main reason for the limited survival rates among lung transplant (LT) recipients. There remains no effective treatment for CR. The aim of this study was to identify new molecular mechanisms involved in CR by using DNA microarray analysis. METHODS: We performed 10 left LTs using the microsurgical cuff technique in inbred Sprague-Dawley rats. Lung isograft samples were obtained 3 months after surgery. We analyzed histologic, apoptotic and gene expression changes by DNA microarray and quantitative PCR analysis. RESULTS: Histologic analyses confirmed signs of CR in all lungs and positive labeling for apoptotic and anti-apoptotic markers. A total of 702 genes were regulated in the CR lungs: 317 genes were upregulated and 385 were downregulated. Significant changes for about 30 biologic processes, including regulation of the cytoskeleton, and 15 signaling pathways, such as adherens junctions, were observed. We found significantly increased mRNA expression of the Cldn5, Epas1, Tgfb1, Vegf, Selp1, Hsp27 and Igf1 genes. CONCLUSIONS: This is the first experimental study performed in an orthotopic model of LT using DNA microarray analysis. The individual genes, biologic process and pathways identified may represent novel targets that could be manipulated and contribute to the development of treatments capable of providing protection from CR. PMID- 22305385 TI - Altered progenitor cell and cytokine profiles in bronchiolitis obliterans syndrome. AB - BACKGROUND: Bone marrow-derived progenitor cells may play a key role in both lung repair and in fibrogenesis. The contribution of CD45(+)collagen-1(+) fibrocytes to fibrosis has been documented elsewhere and recently identified epithelial-like progenitor cells marked by Clara cell secretory protein (CCSP(+)) may be protective after lung injury. Interplay between these populations has not yet been studied in bronchiolitis obliterans syndrome (BOS) post-lung transplant. METHODS: In a cross-sectional design, blood samples were analyzed for CCSP(+) cells and CD45(+)collagen-1(+) fibrocytes by flow cytometry. Plasma cytokines were analyzed by multiplex array. RESULTS: A higher proportion of circulating fibrocytes was measured in patients with BOS Grade >=1 than in those with BOS Grade 0(p). In parallel, a lower proportion of CCSP(+) cells was found in BOS >=1 patients compared with BOS 0(p) and non-transplant controls, resulting in an altered cell ratio between the groups. A higher ratio of CD45(+)collagen-1(+) to CCSP(+) cells was associated with greater airflow limitation based on FEV(1) and FEV(1)/FVC ratio. No relationship between cell profiles and time post-transplant was found. Plasma analysis showed an increase in key stem cell and inflammatory cytokines in both groups post-transplant, whereas stromal-derived factor-1 and vascular endothelial growth factor were increased in cases of BOS >=1 specifically. Plasma stromal-derived factor-1 levels also correlated with fibrocytes post-transplant. CONCLUSIONS: Overall, altered progenitor cell profiles were found in patients who developed advanced BOS, which may be mediated by alterations in circulating cytokines. Ultimately, measurement of progenitor cell profiles may lead to further insight into the pathogenesis of airflow obstruction after lung transplantation. PMID- 22305386 TI - Combined heart and liver transplantation in an adult with familial heterozygous hypercholesterolemia and severe ischemic cardiomyopathy. PMID- 22305387 TI - Disseminated infection caused by novel species of Microsporidium, Thailand. AB - We describe a case of microsporidial myositis in a healthy man from Thailand. The small subunit rRNA sequence of this microsporidium is novel and has a close phylogenetic relationship with Endoreticulatus, a genus of lepidopteran microsporidia. Myositis could be caused by more genera of microsporidia than previously known. PMID- 22305388 TI - Nontuberculous mycobacteria in tap water. PMID- 22305389 TI - Novel amperometric assay for drug-DNA interaction based on an inhibitory effect on an electrocatalytic activity of DNA-Cu(II) complex. AB - A novel strategy of amperometric assay for drug-dsDNA interactions was developed based on an inhibitory effect of antimararial drug (quinacrine) on an electrocatalytic activity of DNA-Cu(II) complex. In this method, a DNA-Cu(II) complex immobilized DNA/polyallylamine(PAA) polyion complex membrane was used as a sensing element. The electrocatalytic activity of a DNA-Cu(II) complex for hydrogen peroxide reduction was reversibly inhibited by electron blocking effect of quinacrine-dsDNA interaction and this inhibitory effect was amplified by the hydrogen peroxide reduction. This phenomenon was utilized for development of a novel amperometric biosensor for DNA-binding drug. From the amperometric current time curves, the response time of the sensor to 20 MUM quinacrine was obtained about 20s, and the detection limit of the quinacrine was found to be 10 MUM estimated to a signal-to-noise ratio of 3.0. Based on the change of steady-state catalytic current, the kinetic analysis of drug-dsDNA interaction can be done in a similar manner of enzyme inhibition, and the binding constant of the quinacrine with DNA can be calculated. This measurement method would be useful for screening of wide variety of DNA-binding drugs and highly toxic pollutants. PMID- 22305390 TI - Inlaid Nd-substituted bismuth titanate nanoplates for protein immobilization and Nd-controlled electrochemical properties. AB - Neodymium (Nd) substituted bismuth titanate (Bi(4-x)Nd(x)Ti(3)O(12), BNTO-x) nanoplates inlaid one another were prepared by sol-gel hydrothermal method, which was explored for protein immobilization and biosensor fabrication. Comparative experiments witnessed that Bi(3+) ions in bismuth titanate (Bi(4)Ti(3)O(12), BTO) were successfully substituted with Nd(3+) ions, and the electrochemical properties of the Hb-Chi-BNTO biosensors closely depended on the Nd(3+) ion content. With increasing the Nd(3+) doping content, the electrochemical performance of the Hb-Chi-BNTO-x biosensors showed regularly variable. Moreover, compared with the Hb-Chi-BTO and other Hb-Chi-BNTO-x biosensors, the Hb-Chi-BNTO 0.85 biosensor had more excellent electrochemical and electrocatalytic properties such as stronger redox peak currents (approximately three-fold), smaller peak-to peak separation (50 mV), larger heterogeneous electron transfer rate (14.1 +/- 3.8s(-1)), higher surface concentration of electroactive redox protein (about 8.16 * 10(-11)mol/cm(2)), and better reproducibility and stability. The Nd depended electrochemical properties of the Hb-Chi-BNTO biosensors may open up a new idea for designing third-generation electrochemical biosensors, and the BNTO 0.85-based biosensor is also expected to find potential applications in many areas such as biomedical, food, and environmental detection. PMID- 22305391 TI - A comparison of solid-phase microextraction (SPME) with simultaneous distillation extraction (SDE) for the analysis of volatile compounds in heated beef and sheep fats. AB - A comparison has been made on the application of SPME and SDE for the extraction of volatile compounds from heated beef and sheep fats with separation and measurement by gas chromatography-mass spectrometry. As far as we know, this report represents the first time that such a comparison has been made for the measurement of volatile compounds in heated sheep fat. Approximately 100 compounds (in relatively high abundance) were characterised in the volatile profiles of heated beef and sheep fats using both techniques. Differences were observed in the volatile profiles obtained from each technique, independent of compound class. Rather than rate one technique as superior to another, the techniques can be regarded as complementary to each other. PMID- 22305392 TI - [Haemophagocytic syndrome in pregnancy: a case report]. AB - Haemophagocytic syndrome (HPS) results from an inappropriate stimulation of macrophages in bone marrow and lymphoid organs, leading to haemophagocytosis and hypercytokinemia. HPS may be primitive, essentially in pediatric population, or secondary to malignancy, infection or autoimmune disease. This disease is rare and prognosis is poor. A small number of cases during pregnancy have been described in literature. We report one HPS case in a pregnant patient at 21 week's gestation with systemic lupus erythematosus. We discuss diagnostic difficulties, obstetrical complications and therapeutic options. PMID- 22305393 TI - [Scheduled caesarean delivery in a patient with vascular type Ehlers-Danlos syndrome]. PMID- 22305394 TI - [The prehospital use of antibiotics in military operations]. AB - War wounds usually show abundant devitalized tissue and often contain foreign material (environmental matter, shrapnels, and bullets). Thus, they are particularly prone to infection. Moreover, evacuation to a medical treatment facility and surgical debridement are often delayed due to tactical constraints. Thus, the early administration of an antibiotic on the ground in a prehospital setting seems justified to slow bacterial growth and the development of early infection. However, antibiotics are never a substitute for surgical treatment. The mix of microorganisms expected in war wounds is highly variable and determines the choice of the antibacterial agent. In a prehospital setting and in the absence of medical or paramedical personnel, the antibiotic must be administered orally (combat pill pack). In view of the antibacterial activity as well as pharmacokinetic and pharmaceutical properties, a combination of a fluoroquinolone active against Pseudomonas and a lincomycine with a high oral bioavailability at high doses seems to be a rational choice (ciprofloxacine 750 mg or alternatively levofloxacine 500 mg+clindamycine 600 mg tablets). If oral administration is excluded (unconsciousness, penetrating abdominal trauma, shock), the parenteral administration will be delayed until the patient has been taken in charge by medical or paramedical personnel. In that case, the intravenous administration of an association of an ureidopenicilline with antibacterial activity against Pseudomonas and a beta-lactamase-inhibitor at high doses could be a rational choice (piperacilline 4 g+tazobactam 0.5 g) (Tazocilline(r)). An antibiotic treatment beyond the time of surgery may become necessary in individual patients depending on the local features of the wound and should be prescribed by the medical officer in charge of the patient on a case-by case basis. PMID- 22305395 TI - [Sudden death and "inverted Tako-Tsubo": think of the brain !]. PMID- 22305396 TI - [Emphysematous pyelonephritis: a rare complication of upper urinary tract infections]. PMID- 22305397 TI - [Regional anaesthesia in obese patient]. AB - OBJECTIVE: To detail specificity of regional anaesthesia techniques in the obese patient. DATA SOURCES: Articles were selected from Medline database using the combination of the following keywords: obesity, peripheral nerve block, spinal anaesthesia, epidural, morbidity, mortality. STUDY SELECTION: Most recent original articles or review have mainly been selected. Some case reports that highlighted specific points were added. DATA EXTRACTION: Articles were analyzed for advantages and drawbacks, and risks of different techniques in obese patient. DATA SYNTHESIS: Techniques avoiding obese patient's mobilization are recommended. The use of skin landmarks may be challenging for both central and peripheral blocks. Ultrasound techniques should improve block performance, even though deep fat layers seem limit sound diffusion. Success rate and incidence of complications are usually increased after regional anaesthesia technique in obese patient. The reduction of intrathecal local anesthetic dose remains controversial in this population. CONCLUSION: Regional anaesthesia techniques could represent an alternative to general anaesthesia (less cardiorespiratory complications). However, many specific considerations have to be taken into account. PMID- 22305398 TI - [Conditions of decision making of admission or non-admission in surgical intensive care unit]. AB - OBJECTIVES: To describe the condition of the decision-making of admission and non admission in intensive care unit. STUDY DESIGN: Non-interventional observational cohort. PATIENTS AND METHODS: Retrospective analysis of declarative terms of decision-making of patients admitted or denied in a surgical intensive care unit. The decision-making in the two admitted or not admitted troops was compared. RESULTS: That it is during a non-admission (149 decisions) or of an admission (149 decisions), the decision-making process was not very different. The instruction of the files was regarded as collegial in nearly 80% of the cases by the intensivist in load. The dialogue precedent the decision utilized generally several speakers but who could be residents. The participation of the patient and/or his close relations, as that of the ancillary medical personnel was rare. No person of confidence or anticipated directive was quoted. More than 50% of the decisions were taken within a time lower than 30 minutes. The decisions of non admission were considered to be more difficult than the decisions of admission. Traceability was not automatically given. CONCLUSION: Thus, this study shows that in its current form the intensivists of the service estimate that in the majority of the cases the instruction of the files was collegial. However, the conditions of seniorisation of the decision, the collection of opinion of the patient and/or his close relations and the traceability are tracks of improvement to be implemented in certain circumstances of admission or non-admission. PMID- 22305399 TI - [Traumatic asphyxia or Perthe's syndrome. About two paediatric cases]. AB - The traumatic asphyxia or Perthes' syndrome is a condition characterized by a classic triad involving head and neck cyanosis, subconjonctival bleeding, and petechiae. The pathophysiology of traumatic asphyxia is different in children compared to adults, because of the greater elasticity of the thorax in children. The purpose of this paper is to describe through two cases of traumatic asphyxia in young children the characteristics of this disease in children. PMID- 22305400 TI - [Transcient improvement of extrapyramidal syndrome after general anaesthesia]. AB - We describe the case of a patient with an untreated Parkinson's disease who underwent surgery for a temporal meningioma. Extrapyramidal syndrome, initially attributed to the meningioma, had improved over the 48 hours following the procedure and then reappeared. This observation raises the question about the impact of drugs used during perioperative days in patients with Parkinson's disease not treated with levodopa. PMID- 22305401 TI - [Interest of echocardiography in the diagnosis and monitoring of a pulmonary embolism complicating a free-floating thrombus in right heart cavities]. AB - We report the case of a 50-year-old patient admitted in ICU for a pulmonary embolism associated with a large thrombus in right heart cavities discovered during an assessment of faintness. Despite an excellent haemodynamic tolerance, there was a systolic and diastolic right ventricular failure and immediate threat to life. The treatment mainly relies on intravenous thrombolysis with excellent results both on thrombus lysis and on the right heart performance. Echocardiography proved to be an essential tool during the management of this patient to ensure the effectiveness and to monitor the whole procedure of thrombolysis. PMID- 22305402 TI - [Severe hydrogen sulfide intoxication: a pediatric case of survival]. AB - We report a paediatric case of survival following severe hydrogen sulfide (H2S) gas intoxication. A 13-year-old boy was found submerged to the neck in a manure tank. He was hypothermic, unresponsive with bilateral mydriasis, and had poor oxygen saturation. After intubation, he was transferred to the paediatric intensive care unit of a tertiary care children's hospital. He developed acute respiratory distress syndrome (ARDS) requiring high frequency percussive ventilation. Cardiac evaluation was significant for myocardial infarction and left ventricular function impairment. He completely recovered from the respiratory and cardiac failure. Neurological examinations showed abnormal signals on MRI in the semi-oval center and in the frontal cortex. Follow-up detected partial impairment of axonal fibers of the right external popliteal sciatic nerve. Paediatric cases of survival after H2S intoxication have been rarely reported. Such exposures can evolve to severe ARDS and benefit from high frequency percussive ventilation. Hypothermia and other metabolic abnormalities are now better explained thanks to actual knowledge about endogenous H2S function. Lessons learned from paediatric accidents should result in better information about this threat for farmers and families living in houses with septic tanks, reducing the risk to their own and their children's safety. PMID- 22305403 TI - [Severe cardiac disturbances after Monkhood ingestion in southern France]. PMID- 22305404 TI - [Normobaric hyperoxia therapy for patients with traumatic brain injury]. AB - Cerebral ischaemia plays a major role in the outcome of brain-injured patients. Because brain oxygenation can be assessed at bedside using intra-parenchymal devices, there has been a growing interest about whether therapeutic hyperoxia could be beneficial for severely head-injured patients. Normobaric hyperoxia increases brain oxygenation and may improve glucose-lactate metabolism in brain regions at risk for ischaemia. However, benefits of normobaric hyperoxia on neurological outcome are not established yet, that hinders the systematic use of therapeutic hyperoxia in head-injured patients. This therapeutic option might be proposed when brain ischemia persists despite the optimization of cerebral blood flow and arterial oxygen blood content. PMID- 22305405 TI - Regulators of protein metabolism are affected by cyclical nutritional treatments with diets varying in protein and energy content. AB - There is evidence that the E3 ubiquitin ligases muscle ring finger-1 (MuRF1) and atrogin-1, which mediate the ubiquitination of certain proteins and thereby their proteolysis, are regulated by cyclical nutritional treatments varying in lysine content. In order to explore further the regulatory mechanisms involved in metabolic adaptation to dietary changes, we investigated the effects of daily variations in energy [2800 (E-) followed by 3200 kcal/kg (E+)], protein [230 (P+) followed by 150g/kg (P-)] or both [E-P+ followed by E+P-] on muscle protein metabolism in 2-week-old male broiler chickens. Growth performance was similar for all treatments. Expression of atrogin-1 and MuRF1 was changed by alternation of diets varying in protein (higher expression with P- vs. P+) and energy content (higher expression with E- vs. E+). The expression of atrogin-1 was regulated with mixed diets (increase in E+P- vs. E-P+) but not that of MuRF1. Such regulation may involve the mammalian target of rapamycin (mTOR), which was more phosphorylated with P+ than with P-. Eukaryotic initiation factor 4E binding protein, p70S6 kinase and ribosomal protein S6, which are mTOR targets known to control protein synthesis, were highly activated by increased protein content (P+ vs. P-). The mechanisms coordinating the protein synthesis/proteolysis balance remain to be characterized. PMID- 22305406 TI - PPARgamma as a molecular target of EPA anti-inflammatory activity during TNF alpha-impaired skeletal muscle cell differentiation. AB - Activated skeletal muscle satellite cells facilitate muscle repair or growth through proliferation, differentiation and fusion into new or existing myotubes. Elevated levels of the proinflammatory cytokine tumor necrosis factor-alpha (TNF alpha) impair this process and are documented to have significant roles in muscle pathology. Recent evidence shows that the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) can block TNF-mediated suppression of progenitor cell differentiation, but the nature of this activity and its significance for local regulation of inflammation are not known. In the current study, we examined differentiation of the C2C12 myoblast line during treatment with TNF-alpha and EPA and measured the expression, activation and inhibition of peroxisome proliferator-activated receptor-gamma (PPARgamma), as several studies have shown its involvement in mediating EPA activity and the inhibition of nuclear factor (NF)-kappaB inflammatory gene activation. We found that TNF-alpha treatment increased NF-kappaB activity and reduced expression and activation of PPARgamma, resulting in impaired myotube formation. EPA treatment attenuated these effects of TNF-alpha and was associated with up-regulation of PPARgamma. Furthermore, EPA inhibited TNF-alpha-mediated transcription and secretion of interleukin (IL)-6, a key target gene of TNF-mediated NF-kappaB transcriptional activity. Pretreatment with a PPARgamma selective antagonist inhibited some of the actions of EPA but was only partially effective in reversing inhibition of IL-6 production. These results show that EPA activity was associated with altered expression and activation of PPARgamma, but exerted through both PPARgamma-dependent and PPARgamma-independent pathways leading to suppression of the proinflammatory cellular microenvironment. PMID- 22305407 TI - Poor sleep as a potential causal factor in aggression and violence. AB - Clinical observations suggest that sleep problems may be a causal factor in the development of reactive aggression and violence. In this review we give an overview of existing literature on the relation between poor sleep and aggression, irritability, and hostility. Correlational studies are supporting such a relationship. Although limited in number, some studies suggest that treatment of sleep disturbances reduces aggressiveness and problematic behavior. In line with this is the finding that sleep deprivation actually increases aggressive behavior in animals and angriness, short-temperedness, and the outward expression of aggressive impulses in humans. In most people poor sleep will not evoke actual physical aggression, but certain individuals, such as forensic psychiatric patients, may be particularly vulnerable to the emotional dysregulating effects of sleep disturbances. The relation between sleep problems and aggression may be mediated by the negative effect of sleep loss on prefrontal cortical functioning. This most likely contributes to loss of control over emotions, including loss of the regulation of aggressive impulses to context appropriate behavior. Other potential contributing mechanisms connecting sleep problems to aggression and violence are most likely found within the central serotonergic and the hypothalamic-pituitary-adrenal-axis. Individual variation within these neurobiological systems may be responsible for amplified aggressive responses induced by sleep loss in certain individuals. It is of great importance to identify the individuals at risk, since recognition and adequate treatment of their sleep problems may reduce aggressive and violent incidents. PMID- 22305408 TI - Block synthesis of A tetrasaccharides (types 1, 3, and 4) related to the human ABO blood group system. AB - Blood group A tetrasaccharides of different types have the same terminal trisaccharide fragment that allows using a block scheme in their synthesis. 3 Aminopropyl glycosides of tetrasaccharides GalNAcalpha1-3(Fucalpha1-2)Galbeta1 3GlcNAcbeta (A type 1), GalNAcalpha1-3(Fucalpha1-2)Galbeta1-3GalNAcalpha (A type 3), and GalNAcalpha1-3(Fucalpha1-2)Galbeta1-3GalNAcbeta (A type 4) were synthesised using acetylated Galalpha1-3(Fucalpha1-2)Gal trichloroacetimidate as a glycosyl donor at the key stage. PMID- 22305409 TI - Synthesis and biological activities of novel isoxazoline-linked pseudodisaccharide derivatives. AB - A series of novel isoxazoline linked pseudodisaccharide derivatives were regiospecifically synthesized by 1,3-dipolar cycloaddition of alpha-allyl-C glycopyranosides and sugar-derived nitrile oxides with good yields. The structures of the compounds were characterized by NMR spectroscopy and MS spectrometry and confirmed by the X-ray crystallographic analysis of compound ((5S)-3-(2,3-O-isopropylidene-5-deoxy-d-lyxofuranose-4-yl)isoxazoline-5-yl) methyl alpha- C-D-galactopyranoside. Their biological activities against glycosidases (alpha-amylase, alpha-glucosidase, and beta-glucosidase) and HIV-RT, and antitumor activity were preliminarily evaluated. Some of them exhibited potent inhibitory activity to HIV-RT. PMID- 22305410 TI - The use of diatom assemblages as ecological indicators in highly stratified estuaries and evaluation of existing diatom indices. AB - Diatom indices are used to evaluate the ecological status of rivers but they have been rarely applied in estuaries. This study aimed to identify the diatom species indicating the main environmental gradients and pressures in a highly stratified estuary; and to evaluate the applicability of existing freshwater diatom indices. Marine influence due to salt-wedge intrusion and sea water mixing appeared as the main factor affecting diatom community. Three diatom assemblages were identified: indicators of riverine conditions (without marine influence), indicators of estuarine conditions (heterogeneous conditions with higher conductivities due to marine influence) and those specifically indicating well-established salt-wedge situations. Nowadays, the main human pressure affecting diatom community in the Ebro Estuary is the hydrological alteration resulting from flow regulation and abstraction. Several limitations were encountered in the application of diatom indices (e.g. inverse response with nutrients; ecologically important species not considered). Therefore, their use in estuaries should be done cautiously. PMID- 22305411 TI - To abort or not? A Greek dilemma--case study. AB - Abortion is a major issue in contemporary Greece as it is often practiced but not debated openly and accordingly. AIM: To present and discuss critically a real case scenario with strong ethical implications concerning abortion under two polar ethical doctrines, i.e. Utilitarianism and Deontologism. DISCUSSION: From a Deontological point of view the baby's life should be spared regardless of reason. In contrast, Utilitarians reason that the effect on the mother and family life should be drawn into the decision equation. The mother, who was heavily influence by her religious beliefs, decided to keep the baby, and the pregnancy continued as planned. CONCLUSION: The importance of weighing up the views of the patient and respecting her autonomy is crucial when dealing with such issues. Health care professionals need to be adequately prepared in order to facilitate and support patients and families in similar circumstances. PMID- 22305412 TI - Effect of surgical site infections with waterless and traditional hand scrubbing protocols on bacterial growth. AB - BACKGROUND: Alcohol-based antiseptic scrub formulation has long been used for hand cleansing in the operating room. Recently, a waterless surgical scrub formulation containing 1% chlorhexidine gluconate was developed to provide a comparable antiseptic effect. The present study explored the scrub time required when using waterless hand scrub and traditional hand scrub formulations for operating room staff and compared bacterial growth on the hands after surgical hand scrubbing in the 2 groups. METHODS: Operating room staff members (n = 100) were recruited randomly from medical centers in Taiwan. Two days in July 2010 were chosen for testing in advance, and the participants were assigned equally to use either a waterless scrub or traditional scrub formulation on 2 separate days. Scrub times were recorded and microorganisms on hands after scrubbing were sampled on 2 separate days. Two days after sampling, the colonies grown on bacterial culture plates were counted and expressed as colony-forming units (CFU) per plate. RESULTS: At 48 hours after sampling, microorganisms were found on 7 of the 50 plates in the waterless scrub group (1-9 CFU) and on 7 of the 50 plates in the traditional scrub group (1-5 CFU). The difference between the groups was no statistically significant (95% CI, 0.85-1.71). Nine surgical patients were found to have contact with the 14 participants with microorganisms found after scrubbing in the operating room. Among these 9 patients, 1 patient with diabetes who underwent amputation developed local reddish swelling suggestive of surgical site infection necessitating a 7-day course of cefalexin. The incidence of surgical site infection was not signifcantly different in the 2 groups. CONCLUSIONS: Our findings suggest that waterless hand scrub is as effective as traditional hand scrub in cleansing the hands of microorganisms and more efficient in terms of scrub time. PMID- 22305413 TI - Prevalence of antibiotic resistance among Acinetobacter baumannii isolates from Aleppo, Syria. AB - This study describes and analyzes Acinetobacter baumannii antibiotic susceptibly profile in Aleppo, Syria, thus providing vital information for guiding treatment of A baumannii infections. Two hundred sixty nonrepetitive A baumannii isolates were studied over 3.5 years. Resistance rates are at the higher end of globally reported levels. Newer cephalosporins and beta-lactamase-resistant agents are becoming practically ineffective. Better activity is limited to carbapenems and colistin, which elicited the highest susceptibility levels. PMID- 22305414 TI - The characteristic expression of B7-associated proteins in Langerhans cell sarcoma. AB - Langerhans cell sarcoma (LCS) is a rare malignancy derived from dendritic cells of the epidermis that is characterized by cytological atypia, frequent mitoses, and aggressive clinical behavior. Cancer-associated B7 molecules including B7-H1, B7-DC, B7-H3 and B7-H4 are thought to be involved in the immunoescape of cancer cells and to function as prognostic markers. However, the expression and distribution of these molecules in LCS have not been described. Here we report that all of these molecules were observed in LCS sample sections by immunohistochemistry analysis. At the cellular level, they were found on the cell membrane and in the cytoplasm. Fluorescence dual staining indicated that B7-H1, B7-H3 and B7-H4 were principally associated with Langerin(+) tumor cells. More interestingly, B7-H1, B7-H3 and B7-H4 were co-expressed on the same tumor cells. Z39Ig, the novel B7-related protein, was also found in the LCS sample sections. Fluorescence dual staining showed that Z39Ig was restricted on CD68(+) macrophages. Our results suggest that B7-H1, B7-H3 and B7-H4 may be potential biomarkers to identify LCS, and a clear understanding of their functional roles may further elucidate the pathogenesis of this carcinoma and potentially contribute to the development of novel immunotherapeutic strategies. PMID- 22305415 TI - Acoustic structure of male loud-calls support molecular phylogeny of Sumatran and Javanese leaf monkeys (genus Presbytis). AB - BACKGROUND: The degree to which loud-calls in nonhuman primates can be used as a reliable taxonomic tool is the subject of ongoing debate. A recent study on crested gibbons showed that these species can be well distinguished by their songs; even at the population level the authors found reliable differences. Although there are some further studies on geographic and phylogenetic differences in loud-calls of nonhuman primate species, it is unclear to what extent loud-calls of other species have a similar close relation between acoustic structure, phylogenetic relatedness and geographic distance. We therefore conducted a field survey in 19 locations on Sumatra, Java and the Mentawai islands to record male loud-calls of wild surilis (Presbytis), a genus of Asian leaf monkeys (Colobinae) with disputed taxanomy, and compared the structure of their loud-calls with a molecular genetic analysis. RESULTS: The acoustic analysis of 100 surili male loud-calls from 68 wild animals confirms the differentiation of P.potenziani, P.comata, P.thomasi and P.melalophos. In a more detailed acoustic analysis of subspecies of P.melalophos, a further separation of the southern P.m.mitrata confirms the proposed paraphyly of this group. In concordance with their geographic distribution we found the highest correlation between call structure and genetic similarity, and lesser significant correlations between call structure and geographic distance, and genetic similarity and geographic distance. CONCLUSIONS: In this study we show, that as in crested gibbons, the acoustic structure of surili loud-calls is a reliable tool to distinguish between species and to verify phylogenetic relatedness and migration backgrounds of respective taxa. Since vocal production in other nonhuman primates show similar constraints, it is likely that an acoustic analysis of call structure can help to clarify taxonomic and phylogenetic relationships. PMID- 22305416 TI - Chronic pneumonia in calves after experimental infection with Mycoplasma bovis strain 1067: characterization of lung pathology, persistence of variable surface protein antigens and local immune response. AB - BACKGROUND: Mycoplasma bovis is associated with pneumonia in calves characterized by the development of chronic caseonecrotic lesions with the agent persisting within the lesion. The purposes of this study were to characterize the morphology of lung lesions, examine the presence of M. bovis variable surface protein (Vsp) antigens and study the local immune responses in calves after infection with M. bovis strain 1067. METHODS: Lung tissue samples from eight calves euthanased three weeks after experimental infection with M. bovis were examined by bacteriology and pathology. Lung lesions were evaluated by immunohistochemical (IHC) staining for wide spectrum cytokeratin and for M. bovis Vsp antigens and pMB67 antigen. IHC identification and quantitative evaluation of CD4+ and CD8+ T lymphocytes and immunoglobulin (IgG1, IgG2, IgM, IgA)-containing plasma cells was performed. Additionally, expression of major histocompatibility complex class II (MHC class II) was studied by IHC. RESULTS: Suppurative pneumonic lesions were found in all calves. In two calves with caseonecrotic pneumonia, necrotic foci were surrounded by epithelial cells resembling bronchial or bronchiolar epithelium. In all calves, M. bovis Vsp antigens were constantly present in the cytoplasm of macrophages and were also present extracellularly at the periphery of necrotic foci. There was a considerable increase in numbers of IgG1- and IgG2 positive plasma cells among which IgG1-containing plasma cells clearly predominated. Statistical evaluation of the numbers of CD4+ and CD8+ T cells, however, did not reveal statistically significant differences between inoculated and control calves. In M. bovis infected calves, hyperplasia of bronchus associated lymphoid tissue (BALT) was characterized by strong MHC class II expression of lymphoid cells, but only few of the macrophages demarcating the caseonecrotic foci were positive for MHC class II. CONCLUSIONS: The results from this study show that infection of calves with M. bovis results in various lung lesions including caseonecrotic pneumonia originating from bronchioli and bronchi. There is long-term persistence of M. bovis as demonstrated by bacteriology and immunohistochemistry for M. bovis antigens, i.e. Vsp antigens and pMB67. The persistence of the pathogen and its ability to evade the specific immune response may in part result from local downregulation of antigen presenting mechanisms and an ineffective humoral immune response with prevalence of IgG1 antibodies that, compared to IgG2 antibodies, are poor opsonins. PMID- 22305417 TI - Successful management of a case of electrical storm due to invasive endocarditis. AB - We present a 44-year-old man with invasive aortic and tricuspid valve endocarditis complicated by electrical storm, which was immediately diagnosed and successfully treated due to the patient's telemetry electrocardiogram (ECG). This case highlights a rare but potentially fatal complication in patients with invasive endocarditis and the need for very careful clinical evaluation and monitoring of these patients. PMID- 22305418 TI - Translational research in the developing world: molecular medicine goes global. PMID- 22305419 TI - Probing quenched dye fluorescence of Cy3-DNA-Au-nanoparticle hybrid conjugates using solution and array platforms. AB - Tuning the luminescence intensity of fluorophores using nanoparticles has shown great potential for the detection of inorganic metal ions, viruses, and proteins. The enhancement or quenching of a dye's fluorescence intensity is strongly dependent on the spatial separation of the dye from the nanoparticle surface. To extend luminescence probing from the solution platform to the solid-state platform, we explored and performed dye quenching assessment using an array format in this study. We report the distance-dependent fluorescence behavior of Au-DNA conjugates prepared by equilibrating phosphine-stabilized gold nanoparticles (AuNPs) of 10-nm size with the designed spacer ds-DNA consisting of thiol-modified target and Cy3-labeled complementary probe of different lengths (5 20 nm). The Cy3-labeled products were immobilized onto MPTMS (3 mercaptopropyltrimethoxysilane)-modified glass substrates and then excited with a 532-nm laser source. Quenching efficiency of AuNPs with increasing Au-to-dye distance was assessed using ligand exchange of the thiolated oligonucleotide by 2 mercaptoethanol (ME) to obtain free Cy3-DNA probe, thus eliminating nanoparticle effect on the dye's luminescence intensity. Effective exchange, revealed by UV vis absorption and fluorescence profiles, was achieved in a few minutes. It was observed that fluorescence quenching of Au-DNA-Cy3 assessed using the array format was consistent with the result in solution phase for the conjugates with up to 10-nm Au-to-Cy3 separation distance. PMID- 22305420 TI - Characterizing zeta potential of functional nanofibers in a microfluidic device. AB - The measurement of surface charge on nanofibers was achieved by characterizing zeta potential of the nanofibers via a newly developed device for streaming current measurement. Low flow rates were sufficient to generate detectable streaming currents in the absence of an externally applied voltage without damaging nanofiber samples. Zeta potential was calculated by using the Helmholtz Smoluchowski equation and the measured streaming currents. Two acrylic plates were machined and assembled to form a microfluidic channel that is 150 MUm high, 2.0mm wide, and 30 mm long. Two electrodes for the measurement of streaming currents were housed in the top plate. Two nanofibers of pure polyacrylonitrile (PAN) fibers and charged (TiO(2) incorporated) PAN fibers were prepared and characterized in the device. Monobasic sodium phosphate and dibasic sodium phosphate were used to prepare four different pH buffer solutions ranging from pH 5 to pH 8 in order to characterize the zeta potentials. The pure PAN nanofibers had negatively-charged surfaces regardless of pH. However, the zeta potentials of PAN/TiO(2) nanofibers changed from positive to negative at pH 6.5. The zeta potential measurements made on the nanofibers in this new microfluidic device matched with those of the powdered raw materials using a commercial Zetasizer. PMID- 22305421 TI - Delayed presentation of posterior urethral valves in discordant twins. AB - Concordant and discordant presentations of posterior urethral valves (PUV) in twins have been described. Twin gestation may complicate the diagnosis of PUV based on prenatal evaluation. A case series of 2 sets of twin births is presented, each of which was discordant for the diagnosis of PUV. A delay in diagnosis occurred in both cases, despite prenatal ultrasound abnormalities. This delay could result from failed sensitivity of prenatal ultrasound or from postnatal evaluation of the incorrect twin. Caution must be exercised during follow-up of abnormalities identified on prenatal ultrasound in diseases in which there are no external distinguishing characteristics. PMID- 22305422 TI - Optimal surgical margin in nephron-sparing surgery for T1b renal cell carcinoma. AB - OBJECTIVE: To determine the optimal surgical margins in nephron-sparing surgery (NSS) for T1b renal cell carcinomas (RCC). MATERIALS AND METHODS: We retrospectively assessed 87 T1b RCC specimens after radical nephrectomy through whole-kidney continuous sections, with 92 T1a RCCs included as controls. The completeness of pseudocapsule (PS) and extra-PS lesions and multifocality were microscopically examined, as was the greatest distance between extra-PS lesions and primary tumors. RESULTS: The rates of incomplete PS (34% [30/87] vs 18% [17/92], P = .015) and positive cancer lesions beyond the PS (39% [34/87] vs 25% [23/92], P = .043) were significantly higher in the T1b than in the T1a group. All extra-PS lesions were located within 3.0 mm of the primary tumor. Multifocal tumors were found in 6% (5/87) of patients with T1b and 5% (5/92) of patients with T1a tumors (P = .928). CONCLUSION: These results indicate that 4 mm may be the optimal surgical margin for NSS for patients with T1b RCC because all extra PS lesions were located within 3 mm of the primary tumors. PMID- 22305423 TI - Ureteropyelostomy using the native ureter for the management of ureteric obstruction or symptomatic reflux following renal transplantation. AB - OBJECTIVE: To evaluate the outcome of ureteropyelostomy using the native ureter for the management of ureteric obstruction or symptomatic reflux after renal transplantation. MATERIALS AND METHODS: This is a single-center retrospective review of consecutive patients who underwent ureteropyelostomy after renal transplantation between the years 2000 and 2009. Ureteropyelostomy was performed using the ipsilateral native ureter. The native kidney was not removed. Patients' baseline characteristics, preceding interventions, and postprocedural outcomes were analyzed. RESULTS: Ten patients underwent ureteropyelostomy after renal transplantation. All had initial Lich Gregoir ureterovesical anastomosis. Reasons for the reconstructive surgery were transplant ureteric stenosis in 8 patients or vesicoureteric reflux causing recurrent graft pyelonephritis in 2 patients. Median follow-up was 53 months (range 24-76). Postoperative complications included 3 patients who had transient anastomotic obstruction after removal of the double pigtail stent. They were managed with short-term ureteric restenting or nephrostomy tube insertion. In addition, 2 patients required delayed ipsilateral native nephrectomy because of infection. At last follow-up, all grafts remained unobstructed and free of infections. CONCLUSION: Ureteropyelostomy using the native ureter for the management of transplant ureteric obstruction or symptomatic reflux is safe and provides good long-term preservation of graft function in selected patients. PMID- 22305424 TI - Clinical analysis of management of pediatric testicular germ cell tumors. AB - OBJECTIVE: To analyze our experiences of pediatric testicular tumors and investigate the management of pediatric testicular germ cell tumors. Pediatric testicular tumors are rare and the treatment of them has not been well defined. METHODS: Children treated for primary testicular tumors between January 1998 and July 2010 were retrospectively analyzed. For yolk sac tumor, the difference of survival rates between patients with and without retroperitoneal lymph node dissection (RPLND) was calculated. RESULTS: Eighty-seven cases met our criteria and 78 were germ cell tumors, including 40 cases with yolk sac tumor. Patients were 3-128 months old (median 19), and 53 patients were diagnosed at younger than 2 years of age. For germ cell tumors, serum alpha-fetoprotein and beta-human chorionic gonadotropin were elevated in 48 and 7 patients, respectively, including 38 and 2 in those with yolk sac tumor. RPLND and chemotherapy were performed in 13 and 19 patients, respectively, and surveillance was performed in 50 patients. With median follow-up of 50 months, 6 patients had recurrence, 4 patients died, and the others achieved complete remission. For stage I yolk sac tumor, the difference of survival rates between patients with and without RPLND was not significant (P = .808). CONCLUSION: Yolk sac tumor is the most common type of pediatric testicular tumor. For stage I yolk sac tumor, radical inguinal orchiectomy is effective, salvage chemotherapy is promising, and RPLND may not be necessary. PMID- 22305425 TI - Leishmania infantum and human visceral leishmaniasis, Argentina. PMID- 22305426 TI - A strategy of gene overexpression based on tandem repetitive promoters in Escherichia coli. AB - BACKGROUND: For metabolic engineering, many rate-limiting steps may exist in the pathways of accumulating the target metabolites. Increasing copy number of the desired genes in these pathways is a general method to solve the problem, for example, the employment of the multi-copy plasmid-based expression system. However, this method may bring genetic instability, structural instability and metabolic burden to the host, while integrating of the desired gene into the chromosome may cause inadequate transcription or expression. In this study, we developed a strategy for obtaining gene overexpression by engineering promoter clusters consisted of multiple core-tac-promoters (MCPtacs) in tandem. RESULTS: Through a uniquely designed in vitro assembling process, a series of promoter clusters were constructed. The transcription strength of these promoter clusters showed a stepwise enhancement with the increase of tandem repeats number until it reached the critical value of five. Application of the MCPtacs promoter clusters in polyhydroxybutyrate (PHB) production proved that it was efficient. Integration of the phaCAB genes with the 5CPtacs promoter cluster resulted in an engineered E.coli that can accumulate 23.7% PHB of the cell dry weight in batch cultivation. CONCLUSIONS: The transcription strength of the MCPtacs promoter cluster can be greatly improved by increasing the tandem repeats number of the core-tac promoter. By integrating the desired gene together with the MCPtacs promoter cluster into the chromosome of E. coli, we can achieve high and stale overexpression with only a small size. This strategy has an application potential in many fields and can be extended to other bacteria. PMID- 22305427 TI - Determining mortality rates attributable to Clostridium difficile infection. AB - To determine accuracy of measures of deaths attributable to Clostridium difficile infection, we compared 3 measures for 2007-2008 in Ontario, Canada: death certificate; death within 30 days of infection; and panel review. Data on death within 30 days were more feasible than panel review and more accurate than death certificate data. PMID- 22305428 TI - Modelling chromatin structure and dynamics: status and prospects. AB - The packaging of genomic DNA into chromatin in the eukaryotic cell nucleus demands extensive compaction. This requires attractive nucleosome-nucleosome interactions to overcome repulsion between the negatively charged DNA segments as well as other constraints. At the same time, DNA must be dynamically accessible to the cellular machinery that operates on it. Recent progress in the experimental characterisation of the higher order structure and dynamics of well defined chromatin fibres has stimulated the attempts at theoretical description of chromatin and the nucleosome. Here we review the present status of chromatin modelling, with particular emphasis on coarse-grained computer simulation models, the role of electrostatic interactions, and discuss future perspectives in the field. PMID- 22305429 TI - Life events and their associations with depression and anxiety in older people with intellectual disabilities: results of the HA-ID study. AB - BACKGROUND: People with intellectual disabilities (ID) may be exposed to more life events due to different living circumstances and limited coping abilities. The frequency of life events may increase with age due to age-related decline, loss of significant others and forced relocations. We studied the occurrence of life events in adults with mild to profound ID aged >= 50 years and their association with depression and anxiety. METHODS: Occurrence and burden of life events were assessed with a checklist of 28 items, completed by professional caregivers. Depression and anxiety were assessed with self-report and informant report screening instruments (n=988) and with a psychiatric interview (n=286). Associations with depression and anxiety were studied for life events in general and for specific life events. RESULTS: 97% of the participants had been exposed to multiple life events during the preceding year and 72% had been exposed to one or more negative life events. The frequency was significantly higher in participants aged 65 years or over, in participants with mild or moderate ID and in participants with depression or anxiety. Minor physical illness and problems with a fellow resident were significantly associated with depression and anxiety, decline or loss of mobility and loss of leisure-time activities with depression and change at work or from work with anxiety. LIMITATIONS: This study was cross sectional and therefore lacks reliable information about causality. CONCLUSIONS: Given the high prevalence of life events and their association with depression and anxiety, life events should be better monitored and, if possible, prevented. PMID- 22305430 TI - Plasma cortisol in first episode drug-naive mania: differential levels in euphoric versus irritable mood. AB - BACKGROUND: Dysregulation of HPA axis has been widely described in subjects with bipolar disorder (BD), including changes in cortisol levels during mood episodes and euthymia. However, most of the studies were done with medicated BD patients with variable length of illness, which was shown to interfere on peripheral cortisol levels. Therefore, the present study aims to evaluate plasma cortisol levels in drug-naive BD subjects during the first manic episode, as well as investigate the relationship between plasma cortisol levels and manic symptomatology. METHODS: Twenty-six drug-naive patients were enrolled meeting criteria for a first manic episode in bipolar I disorder. Severity of mania was assessed using the Young Mania Rating Scale (YMRS). The control group included 27 healthy subjects matched by age and gender. Cortisol was quantified using a direct radioimmunoassay. RESULTS: Plasma cortisol levels were decreased during first manic episode compared to healthy controls. Higher cortisol levels were positively associated with the presence of irritability (dysphoria), while elated mania showed lower cortisol levels compared to controls. LIMITATION: Data including larger samples are lacking. CONCLUSION: Higher cortisol in dysphoric mania compared to predominantly elated/euphoric mania may indicate a clinical and neurobiological polymorphic phenomenon, potentially involving a higher biological sensitivity to stress in the presence of irritable mood. The present findings highlight the importance to add a dimensional approach to the traditional categorical diagnosis for future neurobiological studies in BD. PMID- 22305431 TI - Acute paronychia. PMID- 22305432 TI - Long-term donor site morbidity after free nonvascularized toe phalangeal transfer. AB - PURPOSE: Free nonvascularized toe phalangeal transfer is an established surgical option for the reconstruction of hypoplastic digits. This study assessed long term morbidity in the feet using this technique. METHODS: We reviewed 40 children treated between 1991 and 2007 by free nonvascularized toe phalangeal transfer. The diagnosis was digital hypoplasia resulting from symbrachydactyly in 33 cases, constriction ring syndrome in 3 cases, thumb hypoplasia in 3 cases, and perinatal subclavian venous thrombosis in 1 case. The patients were followed up after surgery for a mean of 10 years (range, 3-19 y). The Oxford Ankle Foot Questionnaire was administered to patients and families to assess patient symptoms and patient and parental satisfaction. We assessed toe length ratio, the presence of visible deformity, and distal hypoplasia of the donor toes clinically and radiographically. RESULTS: Emotional problems related to foot appearance were common. We also found functional problems with footwear in some patients. All patients had floppy unstable toes with visible deformity. Increasing foot deformity was seen with growth, which led to deterioration in foot aesthetics, particularly where multiple donor toes had been harvested. We identified distal and middle phalangeal and metatarsal hypoplasia in the donor toes. CONCLUSIONS: Donor site morbidity for free toe phalangeal transfer is greater than previously documented. This should be considered during surgical decision making for reconstruction of hypoplastic digits. Preoperative counseling should include discussion regarding possible consequences of phalangeal harvest on donor toes and options for donor site reconstruction. Long-term follow-up of the donor site is essential to accurately assess results. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III. PMID- 22305433 TI - Recurrence of a giant cell tumor of the hand after 42 years: case report. AB - Giant cell tumors of bone in the hand are rare. We present a case of a recurrent giant cell tumor in the metacarpal 42 years after intralesional excision and autogenous bone grafting. The possibility of recurrent disease should be considered in the evaluation of any patient presenting with new onset of pain at the site of a previously addressed giant cell tumor. Management of these recurrent lesions should include wide excision with digit salvaging procedures or ray amputation owing to the high rates of treatment failures seen with marginal excision. PMID- 22305434 TI - Epinephrine and hand surgery. PMID- 22305435 TI - Recovery room radiographs after total hip arthroplasty: tradition vs utility? AB - Routine inpatient radiographs after total hip arthroplasty can be taken in the recovery room immediately after surgery or in the radiology suite later in the hospital stay. In a review of 632 consecutive recovery room series, we found that 17% of series were inadequate to detect technical issues. We identified technical issues on 12 series (1.9%) and technical issues that impacted inpatient management on 2 series (0.3%). One of these 2 was a dislocation that was detected clinically before imaging. The other was a medial penetration of an acetabular screw that probably did not require the immediate revision that it received. Findings suggest that the single routine inpatient series should be taken in the radiology suite, rather than in the recovery room. PMID- 22305436 TI - Changes in lower extremity 3-dimensional load-bearing axes before and after mobile-bearing total knee arthroplasty. AB - This study evaluated changes in the lower extremity 3-dimensional load-bearing mechanical axes in the anteroposterior and mediolateral directions before and at 3 weeks after mobile-bearing total knee arthroplasty. The effects of the degrees of anteroposterior constraint of the designs on the location of the load-bearing mechanical axis at the knee joint level were also assessed. We evaluated 151 knees from 134 patients with 74 knees receiving meniscal bearing-type and 77 knees receiving rotating platform-type prostheses. In the mediolateral direction, both designs showed significant improvements, whereas in the anteroposterior direction, they revealed no improvements postoperatively and were worsened significantly in meniscal bearing type. Differences in the degree of bone and soft tissue involvement for the correction of alignment may explain the findings. PMID- 22305437 TI - Evaluation of spontaneous third ventriculostomy by three-dimensional sampling perfection with application-optimized contrasts using different flip-angle evolutions (3D-SPACE) sequence by 3T MR imaging: preliminary results with variant flip-angle mode. AB - PURPOSE: This prospective study aimed to evaluate the use of three-dimensional sampling perfection with application-optimized contrasts using different flip angle evolutions (3D-SPACE) in the diagnosis of spontaneous third ventriculostomy (STV) and to compare it with phase-contrast cine magnetic resonance imaging (PC MRI). METHODS: PC-MRI and 3D-SPACE images were obtained in 15 patients with hydrocephalus for evaluation of STV as well as in 10 control cases. The presence of STV was evaluated visually by two experienced radiologists on both PC-MRI and 3D-SPACE images, and the results were statistically compared. RESULTS: There was a strong correlation between PC-MRI and SPACE scores for both readers (correlation coefficient [r]=0.784; P=0.001). There was also a good correlation between PC-MRI scores and consensus-based results. Interobserver reliabilities were strong for all STV scores. In addition, there was excellent correlation between 3D-SPACE scores and consensus-based results (first reader's kappa value: 0.87; second reader's kappa value: 1). CONCLUSION: 3D-SPACE can provide morphological-physiological information for the evaluation of STV with no need for additional PC-MRI analysis or other sequences. As a non-invasive test, it can also be included among the first line of choices of MRI sequences for patients with obstructive hydrocephalus. PMID- 22305438 TI - WISE (Workshop on Injection Safety in Endocrinology) recommendations. Editorial. PMID- 22305439 TI - Synopsis of the WISE meeting. PMID- 22305440 TI - WISE recommendations to ensure the safety of injections in diabetes. AB - AIM: Injections and fingersticks administered to patients with diabetes in health care settings present a risk of blood exposure to the injector as well as other workers in potential contact with sharps. Such exposures could lead to transmission of bloodborne pathogens such as hepatitis and HIV. A recent EU Directive requires that where such risks have been identified, processes and devices must be put in place to reduce or eliminate the risk. The aim of this paper is to provide formal guidelines on the application of this Directive to diabetes care settings. These evidence-based recommendations were written and vetted by a large group of international safety experts. METHODS: A systematic literature search was conducted for all peer-reviewed studies and publications which bear on sharps safety in diabetes. Initially a group of experts reviewed this literature and drafted the recommendations. These were then presented for review, debate and revision to 57 experts from 14 countries at the WISE workshop in October, 2011. After the WISE meeting, the revised Recommendations were circulated electronically to attendees on three occasions, each time in a new iteration with revisions. RESULTS: Each recommendation was graded by the weight it should have in daily practice and by its degree of support in the medical literature. The topics covered include Risks of Sharps Injury and Muco-cutaneous Exposure, The EU Directive, Device Implications, Injection Technique Implications, Education and Training (Creating a "Safety Culture"), Value, Awareness and Responsibility. CONCLUSION: These safety recommendations provide practical guidance and fill an important gap in diabetes management. If followed, they should help ensure safe, effective and largely injury-free injections and fingersticks. They will serve as the roadmap for applying the new EU Directive to diabetes care. PMID- 22305441 TI - Needlestick injuries in European nurses in diabetes. AB - AIM: With the June 2010 publication of EU Council Directive 2010/32/EU scrutiny is now being focused on the safety and protection of diabetes nurses. METHODS: We used a questionnaire to study the frequency and risks of Needlestick Injuries (NSI) associated with diabetic injections in European hospitals. 634 nurses participated from 13 western European countries and Russia. RESULTS: When patients with diabetes who self-inject at home are hospitalized injections are given always by the staff in 31% of cases, by the patients themselves where possible in 33%, initially by staff, then the patient takes over in 12% and both staff and patient throughout the stay in 21%. 86% of nurses said their hospitals had a written policy on the prevention of NSI but, where it was available, only 56% were familiar with it. 67% of the nurses had not attended any training on the prevention of NSI and only 13% had attended one in the last year. 7.1% of nurses report recapping needles and 5.9% report storing unprotected needles temporarily on a tray, trolley or cart. 32% of nurses report suffering a NSI while giving a diabetic injection at some point in the past. 29.5% of NSI occurred while recapping a used needle. 57% of nurses unscrew pen needles using their own fingers. In 80% cases the source patient's identity was known and the sharp item was "contaminated" (known previous percutaneous exposure to patient) in almost half the cases (43%). NSIs were reported to the proper authorities in only 2/3 of cases. CONCLUSION: Our study shows that frequent NSI occur in European nurses treating people with diabetes in hospital settings. These injuries are a source of possible infection despite the small size of diabetes needles. The introduction of safety-engineered medical devices has been shown to reduce the risk of injury. A new European Directive that has now come into force specifically stipulates that wherever there is risk of sharps injury, the user and all healthcare workers must be protected by adequate safety precautions, including the use of "medical devices incorporating safety-engineered protection mechanisms". PMID- 22305442 TI - Exonuclease III-based and gold nanoparticle-assisted DNA detection with dual signal amplification. AB - Herein we report a sensitive electrochemical biosensor for DNA detection by making use of exonuclease III and probe DNA functionalized gold nanoparticles. While probe DNA P1 modified on a gold electrode surface can self-hybridize into a stem-loop structure with an exonuclease III-resistant 3' overhang end, in the presence of target DNA, P1 may also hybridize with the target DNA to form a duplex region. Therefore, exonuclease III may selectively digest P1 from its 3' hydroxyl termini until the duplex is fully consumed. Since a single target DNA can trigger exonuclease III digestion of numerous P1 strands, the first signal amplification is achieved. On the other hand, since the digested P1, exposing its complementary sequence to probe DNA P2, can further hybridize with P2 that has been previously modified on the surface of gold nanoparticles, many nanoparticles loaded with numerous DNA strands are immobilized onto the electrode surface. Consequently, large amount of electroactive molecules [Ru(NH(3))(6)](3+) can bind with the DNA strands to produce an intense electrochemical response as the second signal amplification. Based on the studies with cyclic voltammetry (CV) and chronocoulometry (CC) techniques, the proposed biosensor can sensitively detect specific target DNA at a picomolar level with high specificity. PMID- 22305443 TI - Triplex signal amplification for electrochemical DNA biosensing by coupling probe gold nanoparticles-graphene modified electrode with enzyme functionalized carbon sphere as tracer. AB - An ultrasensitive electrochemical DNA biosensor was constructed by assembling probe labeled gold nanoparticles (ssDNA-AuNP) on electrochemically reduced graphene oxide (ERGO) modified electrode with thiol group tagged (GT) DNA strand (d(GT)(29)SH) and coupling with horseradish peroxidase (HRP) functionalized carbon sphere (CNS) as tracer. The heteronanostructure formed on the biosensor surface appeared relatively good conductor for accelerating the electron transfer, while the HRP tagged CNS provided dual signal amplification for electrochemical biosensing. The triplex signal amplification strategy produced an ultrasensitive electrochemical detection of DNA down to attomolar level (5 aM) with a linear range of 5 orders of magnitude (from 1 * 10(-17)M to 1 * 10(-13)M), and appeared high selectivity to differentiate single-base mismatched and three base mismatched sequences of DNA. The proposed approach provided a simple and reliable method for DNA detection with high sensitivity and specificity, indicating promising application in bioanalysis and biomedicine. PMID- 22305444 TI - Silicon photomultiplier (SPM) detection of low-level bioluminescence for the development of deployable whole-cell biosensors: possibilities and limitations. AB - Whole-cell bacterial bioreporters await miniaturized photon counting modules with high sensitivity and robust compatible hardware to fulfill their promise of versatile, on-site biosensor functionality. In this study, we explore the photon counting readout properties of the silicon photomultiplier (SPM) with a thermoelectric cooler and the possibilities of detecting low-level bioluminescent signals. Detection performance was evaluated through a simulated LED light source and the bioluminescence produced by the genetically engineered Pseudomonas fluorescens bacterial bioreporter 5RL. Compared with the conventional photomultiplier tube (PMT), the results revealed that the cooled SPM exhibits a wider linear response to inducible substrate concentrations (salicylate) ranging from 250 to 5000 ppb. Although cooling of the SPM lowered dark count rates and improved the minimum detectable signal, and the application of a digital filter enhanced the signal-to-noise ratio, the detection of very low light signals is still limited and remains a challenge in the design of compact photon counting systems. PMID- 22305445 TI - Ultrasensitive electrochemical immunosensor for HE4 based on rolling circle amplification. AB - A novel electrochemical immunoassay system for the detection of human epididymis specific protein 4 (HE4) was developed. A chitosan-titanium carbide (TiC) nanocomposition film was first electrodeposited onto a tin-doped indium oxide (ITO) electrode at a constant potential. Gold (Au) nanoparticles were then electrodeposited on the surface of the chitosan-TiC film by cyclic voltammetry (CV). The capture antibody (anti-HE4) was adsorbed onto the Au and TiC nanoparticles. After a specific sandwich immunoreaction among the capture antibody, HE4, and biotinylated secondary antibody, biotinylated primer DNA was immobilized on the secondary antibody by biotin-streptavidin system. Appropriate amounts of circular template DNA and biotinylated primer DNA were used for rolling circle amplification (RCA) under optimal conditions. The RCA products provided a large number of sites to link DNA detection probes. Doxorubicin hydrochloride intercalated the CG-GC steps between the RCA products and the DNA detection probes, which was monitored by differential pulse voltammetry (DPV) based on the current signal of doxorubicin hydrochloride. With the above mentioned amplification factors, the current responded to HE4 linearly in the concentration range of 3-300 pM under optimal detection conditions, with a detection limit of 0.06 pM. Stepwise changes in the microscopic features of the surfaces and electrochemical properties upon the formation of each layer were confirmed by scanning electron microscopy (SEM), atomic force microscopy (AFM), and electrochemical impedance spectroscopy (EIS). This system was successfully employed for the detection of HE4 with good accuracy and renewable ability. PMID- 22305446 TI - Reprint of: Burn wound healing time assessed by laser Doppler imaging. Part 2: Validation of a dedicated colour code for image interpretation. AB - INTRODUCTION: Laser Doppler imaging (LDI) has been investigated and used since 1993 for the assessment of burn wounds. Here we describe tests that validate use of the dedicated colour palette, derived in Part 1, for a standardised interpretation of LDI images for prediction of healing time (<14 days, 14-21 days or >21 days). We also describe clinical and technical factors to be taken into account during LDI imaging and during image interpretation. METHODS: (1) A cohort of images, selected at random, were assessed, according to strict rules of interpretation, by 6 clinicians against photographs of healing, for accuracy of healing time prediction and clinical usefulness using five-point scales. (2) All images were assessed technically in a similar way for accuracy and the accuracy was further studied by analysing the data by ordinal logistic regression to predict the dependence of burn injury healing time on demographic variables (age, sex, race, %TBSA, burn injury cause and site). (3) Where average LDI blood flow could be determined, regression analysis was used to assess the potential accuracy of the technique. RESULTS: (1) Clinical accuracy was found to be 93% and usefulness was 89%; (2) technical accuracy was found to be 96%; (3) regression analysis found that a potential accuracy of 90.9% could be achieved using LDI results alone, increasing to 92% if gender was also considered; no other parameters had an influence on healing time prediction. CONCLUSION: LDI can be used in a standardised way as a valid tool for improving on clinical assessment of burn wounds. This can enable earlier appropriate management. PMID- 22305447 TI - Incidentalomas. Preface. PMID- 22305448 TI - Incidentalomas: a "disease" of modern imaging technology. AB - The evolution of new diagnostic techniques has revolutionized the practice of medicine and in fact, the nature of medicine itself. Technology has also expanded the "visual" field of medicine: the naked eye was assisted by the light microscope and then electron microscope to see smaller and smaller features while radiology has permitted "non-invasive" identification of internal structures. However, there are unintended consequences one of which is the discovery of an anomaly during the course of looking for something else - incidental findings and incidentalomas. Technology in general and imaging specifically offer much in service to physicians and their patients. However, it behoves physicians to ensure that technology supplements but does not replace good clinical judgment. This essay aims to put the issue of incidental findings related to advancing technology (especially imaging technology) into a broader context. PMID- 22305449 TI - Evidence-based endocrinology: illustrating its principles in the management of patients with pituitary incidentalomas. AB - Incidentally discovered pituitary lesions are commonly encountered in the current era of ever-increasing imaging. Individualizing a particular approach implies a thorough analysis of existing evidence and balancing it against different patient expectations. We will illustrate the application of principles of Evidence-Based Medicine to a case of a pituitary incidentaloma by formulating questions that are important to patient care and finding related evidence. Our objective is to reflect the opportunities and the challenges that an evidence-based clinical approach offers to clinicians and patients. PMID- 22305450 TI - Radiological evaluation of adrenal incidentalomas: current methods and future prospects. AB - Incidental adrenal lesions are very common. Computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) all have a role to play in characterizing adrenal lesions. The purpose of this review is to discuss the rationale behind both established and emerging imaging techniques. We also discuss how to follow up incidentally found lesions. PMID- 22305451 TI - Advances in pituitary imaging technology and future prospects. AB - There have been substantial advances in pituitary imaging in the last half century. In particular, magnetic resonance imaging is now established as the imaging modality of choice, providing high quality images of the hypothalamic pituitary axis and adjacent structures. More recent technological advances, such as the emergence of 3 Tesla MRI, are already being widely incorporated into imaging practice. However, other advanced techniques, including a variety of potential imaging biomarkers, still require further research to evaluate their potential and define their precise role. The recent development of intraoperative MRI appears promising and may have the potential to improve the outcome of pituitary surgery. Modern high quality imaging inevitably leads to the discovery of incidental lesions, including those within the pituitary gland, although it also plays a central role in their subsequent evaluation and management. PMID- 22305452 TI - Pituitary incidentaloma. AB - Pituitary incidentalomas (PIs) are commonly encountered in clinical practice. While most are microincidentalomas (<1 cm) and not functional, in some cases their identification may lead to discovery of unrecognized abnormalities such as pituitary hormonal deficiencies, excess hormone secretion or visual field defects. Although the majority are pituitary adenomas, the potential list of differential diagnosis is extensive. A limited biochemical work up for asymptomatic patients with microincidentalomas, to include measurement of prolactin and IGF-1, is reasonable, with further studies to be tailored based on the clinical picture. All patients with macroincidentalomas (>=1 cm) should be evaluated for hypopituitarism and undergo visual field testing if the sellar mass abuts or compresses the optic chiasm. Most PIs can be followed, closely without surgery over time, but some may require surgical removal, especially if they are found to be macroincidentalomas at presentation, encroaching on or abutting the optic chiasm, or are found to be functional, excluding prolactinomas. Recovery of pituitary function may be seen in some patients with mass effect following resection of a sellar mass. The association of headache and pituitary incidentalomas remains a diagnostic challenge. There are no randomized controlled studies to guide the follow up approach when surgery is not indicated; most of the follow up algorithms in the literature are based on personal experience. Most retrospective series on natural history indicate that microincidentalomas tend not to grow; without a need for long-term follow up unless the patient becomes symptomatic. Macroincidentalomas, on the other hand, have a propensity to grow and need a more aggressive follow up approach to minimize morbidity. PMID- 22305453 TI - Adrenal incidentalomas. AB - The term adrenal incidentaloma (AI) is usually defined as an adrenal mass unexpectedly detected through an imaging procedure performed for reasons a priori unrelated to adrenal dysfunction or suspected dysfunction. The preferred approach to their management in terms of diagnosis, follow-up, and treatment remain controversial despite a state-of-the-science conference sponsored by the U.S. National Institutes of Health. Although most experts' recommendations tend to be relatively minor variations of the conference's approach, dissenting voices have been heard. Despite their frequent appearance, the challenge remains to recognize and treat the small percentage of AI that do pose a significant risk, either because of their hormonal activity or because of their malignant histology, while leaving the rest alone. Although the differential diagnosis of an incidentally discovered mass is quite extensive, most AIs are non-secreting cortical adenomas. The noninvasive differentiation of benign and malignant lesions depends upon imaging characteristics, and sometimes radiologic diagnosis can be definitive, but often it is not, Among function lesions, autonomous cortisol production seems to be the most common and may be associated with increased cardiovascular risk and clinical features of the "metabolic syndrome." Follow-up of cases in which a specific diagnosis is not made initially involves assessment for growth and development of hormonal function, but even here, controversy about the extent of evaluation persists. PMID- 22305454 TI - Thyroid incidentaloma. AB - Thyroid incidentaloma is defined as an unsuspected, asymptomatic thyroid lesion that is discovered on an imaging study or during an operation unrelated to the thyroid gland. Thyroid incidentalomas are most commonly detected on ultrasound, followed in frequency by computed tomography (CT) and magnetic resonance imaging (MRI), carotid duplex scanning and 2-(18)[F] fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET). The incidence of carcinoma in incidentally discovered thyroid disease is not insignificant. There are significant shortcomings of CT, MRI and PET imaging of the thyroid gland. As result, a thorough sonographic evaluation of the thyroid gland should be performed in all patients with a thyroid incidentaloma, regardless of the radiographic features identified on the "non thyroid "imaging modality. A sonographically confirmed thyroid nodule should be managed in an identical fashion to a clinically apparent thyroid nodule. PMID- 22305455 TI - Pancreatic incidentalomas. AB - Pancreatic incidentalomas are defined as asymptomatic pancreatic lesions, discovered incidentally by imaging for an unrelated indication. They are being discovered with increasing frequency as the use of high quality cross sectional imaging is becoming more widespread. These lesions cover a wide spectrum of pathology from benign simple cysts through potentially malignant lesions such as intraductal papillary mucinous neoplasia, to frankly malignant adenocarcinoma. In this article we outline the incidence, imaging characteristics and natural history of the various incidental lesions with emphasis to neuroendocrine tumors. A diagnostic approach is also suggested, including the rational use of further imaging, serum biochemistry and the utility of ultrasound guided aspiration of cyst fluid if present. We examine several proposed classification systems and discuss the role of surgery, surveillance and prognosis. PMID- 22305456 TI - Ovarian incidentaloma. AB - Incidental adnexal masses occur with relatively high frequency in post-menopausal women, with a prevalence rate of 3.3-18% in asymptomatic patients. Unilocular, benign-appearing ovarian cysts represent the vast majority of abnormal findings at transvaginal ultrasonography. As many as 80% will resolve over a period of several months; if persistent, unchanged, less than 10 cm, and with normal CA-125 values, the likelihood of an invasive cancer is sufficiently low that observation should be offered. More recent investigations support the use of secondary imaging modalities such as MRI, which may help differentiate benign from malignant masses. Surgical management plays a key role when patients are symptomatic regardless of age, menopausal and have documented changes in cyst characteristics, experience elevations in tumor markers or have symptoms suggestive of a hormone-producing neoplasm. High level, evidence-based screening guidelines have yet to be developed. PMID- 22305457 TI - Beneficial effects of ischemic preconditioning on pancreas cold preservation. AB - Ischemic preconditioning (IPC) confers tissue resistance to subsequent ischemia in several organs. The protective effects are obtained by applying short periods of warm ischemia followed by reperfusion prior to extended ischemic insults to the organs. In the present study, we evaluated whether IPC can reduce pancreatic tissue injury following cold ischemic preservation. Rat pancreata were exposed to IPC (10 min of warm ischemia followed by 10 min of reperfusion) prior to ~18 h of cold preservation before assessment of organ injury or islet isolation. Pancreas IPC improved islet yields (964 +/- 336 vs. 711 +/- 204 IEQ/pancreas; p = 0.004) and lowered islet loss after culture (33 +/- 10% vs. 51 +/- 14%; p = 0.0005). Islet potency in vivo was well preserved with diabetes reversal and improved glucose clearance. Pancreas IPC reduced levels of NADPH-dependent oxidase, a source of reactive oxygen species, in pancreas homogenates versus controls (78.4 +/- 45.9 vs. 216.2 +/- 53.8 RLU/MUg; p = 0.002). Microarray genomic analysis of pancreata revealed upregulation of 81 genes and downregulation of 454 genes (greater than twofold change) when comparing IPC-treated glands to controls, respectively, and showing a decrease in markers of apoptosis and oxidative stress. Collectively, our study demonstrates beneficial effects of IPC of the pancreas prior to cold organ preservation and provides evidence of the key role of IPC-mediated modulation of oxidative stress pathways. The use of IPC of the pancreas may contribute to increasing the quality of donor pancreas for transplantation and to improving organ utilization. PMID- 22305458 TI - Sixty years of blood transfusion: a memoir. AB - Paul Schmidt was born in 1925 into the Greatest Generation. Events during military service decided him on the study of medicine. Early research training in red cell preservation that continued during his medical studies opened a 20-year career at the National Institutes of Health (NIH). Beginning in 1954 at the Blood Bank of the NIH Clinical Center, he had exposure to the pioneers who had translated transfusion's wartime beginnings into civilian applications. Work inside the unique NIH clinical research atmosphere together with many of his students provided a fertile field for the growth of what has become transfusion medicine. Topics described range from early studies on platelets and on hepatitis to the background in Washington health politics leading to the National Blood Policy. National and global organizational activity and a second career in community blood service added to his 65 years of experience. The story as transfusion history is presented as a template for future progress. PMID- 22305459 TI - Young children overimitate in third-party contexts. AB - The exhibition of actions that are causally unnecessary to the outcomes with which they are associated is a core feature of human cultural behavior. To enter into the world(s) of their cultural in-group, children must learn to assimilate such unnecessary actions into their own behavioral repertoire. Past research has established the habitual tendency of children to adopt the redundant actions of adults demonstrated directly to them. Here we document how young children will do so even when such actions are modeled to a third person regardless of whether children are presented with the test apparatus by the demonstrating, and assumedly expert, adult or by the observing, and assumedly naive, adult (Experiment 1), whether or not children had opportunity to discover how the apparatus works prior to modeling (Experiment 1), and whether or not children's attention was drawn to the demonstration while they were otherwise occupied (Experiment 2). These results emphasize human children's readiness to acquire behavior that is in keeping with what others do, regardless of the apparent efficiency of the actions employed, and in so doing to participate in cultural learning. PMID- 22305460 TI - Analysis of the SOS response of Vibrio and other bacteria with multiple chromosomes. AB - BACKGROUND: The SOS response is a well-known regulatory network present in most bacteria and aimed at addressing DNA damage. It has also been linked extensively to stress-induced mutagenesis, virulence and the emergence and dissemination of antibiotic resistance determinants. Recently, the SOS response has been shown to regulate the activity of integrases in the chromosomal superintegrons of the Vibrionaceae, which encompasses a wide range of pathogenic species harboring multiple chromosomes. Here we combine in silico and in vitro techniques to perform a comparative genomics analysis of the SOS regulon in the Vibrionaceae, and we extend the methodology to map this transcriptional network in other bacterial species harboring multiple chromosomes. RESULTS: Our analysis provides the first comprehensive description of the SOS response in a family (Vibrionaceae) that includes major human pathogens. It also identifies several previously unreported members of the SOS transcriptional network, including two proteins of unknown function. The analysis of the SOS response in other bacterial species with multiple chromosomes uncovers additional regulon members and reveals that there is a conserved core of SOS genes, and that specialized additions to this basic network take place in different phylogenetic groups. Our results also indicate that across all groups the main elements of the SOS response are always found in the large chromosome, whereas specialized additions are found in the smaller chromosomes and plasmids. CONCLUSIONS: Our findings confirm that the SOS response of the Vibrionaceae is strongly linked with pathogenicity and dissemination of antibiotic resistance, and suggest that the characterization of the newly identified members of this regulon could provide key insights into the pathogenesis of Vibrio. The persistent location of key SOS genes in the large chromosome across several bacterial groups confirms that the SOS response plays an essential role in these organisms and sheds light into the mechanisms of evolution of global transcriptional networks involved in adaptability and rapid response to environmental changes, suggesting that small chromosomes may act as evolutionary test beds for the rewiring of transcriptional networks. PMID- 22305461 TI - Novel spectrophotometric method for determination of cinacalcet hydrochloride in its tablets via derivatization with 1,2-naphthoquinone-4-sulphonate. AB - This study represents the first report on the development of a novel spectrophotometric method for determination of cinacalcet hydrochloride (CIN) in its tablet dosage forms. Studies were carried out to investigate the reaction between CIN and 1,2-naphthoquinone-4-sulphonate (NQS) reagent. In alkaline medium (pH 8.5), an orange red-colored product exhibiting maximum absorption peak (lambdamax) at 490 nm was produced. The stoichiometry and kinetic of the reaction were investigated and the reaction mechanism was postulated. This color developing reaction was employed in the development of a simple and rapid visible spectrophotometric method for determination of CIN in its tablets. Under the optimized reaction conditions, Beer's law correlating the absorbance with CIN concentration was obeyed in the range of 3 - 100 MUg/ml with good correlation coefficient (0.9993). The molar absorptivity (epsilon) was 4.2 * 105 l/mol/cm. The limits of detection and quantification were 1.9 and 5.7 MUg/ml, respectively. The precision of the method was satisfactory; the values of relative standard deviations (RSD) did not exceed 2%. No interference was observed from the excipients that are present in the tablets. The proposed method was applied successfully for the determination of CIN in its pharmaceutical tablets with good accuracy and precisions; the label claim percentage was 100.80 - 102.23 +/- 1.27 1.62%. The results were compared favorably with those of a reference pre validated method. The method is practical and valuable in terms of its routine application in quality control laboratories. PMID- 22305463 TI - Plasmodium falciparum in asymptomatic immigrants from sub-Saharan Africa, Spain. PMID- 22305464 TI - Identification of Familial Adenomatous Polyposis carriers among children with desmoid tumours. AB - OBJECTIVE: Desmoid tumours are rare mesenchymal tumours with unpredictable progression and high recurrence risk. They can occur sporadically or in association with Familial Adenomatous Polyposis (FAP), which is caused by germline APC mutations. The Wnt/beta-catenin pathway has a central role in the pathogenesis of desmoid tumours. These tumours can occur due to either a somatic CTNNB1 or APC mutation but can also be the first manifestation of FAP. Because germline APC analysis is not routinely performed in children with desmoid tumours, the diagnosis FAP may escape detection. The aim of this study is to form guidelines for the identification of possible APC germline mutation carriers among children with desmoid tumours, based on CTNNB1 mutation analysis and immunohistochemical analysis (IHC) for beta-catenin. PATIENTS AND METHODS: We performed IHC of beta-catenin and mutation analysis of CTNNB1 and APC in 18 paediatric desmoid tumours, diagnosed between 1990 and 2009 in the Erasmus MC, Rotterdam. RESULTS: In 11 tumours, IHC showed an abnormal nuclear beta-catenin accumulation. In this group a CTNNB1 mutation was detected in seven tumours. In two tumours with an abnormal nuclear beta-catenin accumulation and no CTNNB1 mutation, an APC mutation was identified, which appeared to be a germline mutation. CONCLUSIONS: Aberrant staining of beta-catenin in paediatric desmoids helps to identify children at risk for FAP. We recommend to screen paediatric desmoid tumours for nuclear localisation of beta-catenin and consequently for CTNNB1 mutations. For patients with nuclear beta-catenin expression and no CTNNB1 mutations, APC mutation analysis should be offered after genetic counselling. PMID- 22305465 TI - Fc gamma receptor polymorphisms as predictive markers of Cetuximab efficacy in epidermal growth factor receptor downstream-mutated metastatic colorectal cancer. AB - BACKGROUND: The immunoglobulin G1 (IgG(1)) monoclonal antibody (MoAb) Cetuximab is active in metastatic colorectal cancer (mCRC) as first or subsequent lines of therapy. Efficacy seems restricted to KRAS wild-type tumours. IgG(1) may also induce antibody dependent cell mediated citotoxicity (ADCC) by recruitment of immune effector cells. ADCC is influenced by Fc gamma receptor (FcgammaR) polymorphisms. We investigated the association of FcgammaR polymorphisms and disease control rate (DCR) in mCRC patients treated with chemotherapy plus Cetuximab. PATIENTS AND METHODS: Tumour tissues from 106 patients were screened for KRAS codon 12 and 13 mutations using a sensitive multiplex assay (DxS, Manchester, United Kingdom). NRAS (codons: 12, 13 and 61), PI3K (exon 20) and BRAF (exon 15) were analysed by direct sequencing. Fcgamma RIIa and Fcgamma RIIIa polymorphisms were genotyped by TaqMan assays. RESULTS: DCR was significantly higher in KRAS wild-type tumours (61% versus 39%, p = 0.049). In epidermal growth factor receptor (EGFR) downstream-mutated mCRC patients, those harbouring an FcgammaRIIa H/H genotype had a higher DCR than alternative genotypes (67% versus 33%, p = 0.017). By multivariate analysis, FcgammaRIIa-131H/H remained significantly correlated with DCR (p = 0.008). CONCLUSION: FcgammaR polymorphisms may play a role in the clinical efficacy of Cetuximab in EGFR downstream mutated mCRC patients. Further research into Cetuximab immune-based mechanisms in KRAS mutated patients seems warranted. PMID- 22305466 TI - Cytoadherence and virulence - the case of Plasmodium knowlesi malaria. AB - BACKGROUND: Cytoadherence of infected red blood cells to brain endothelium is causally implicated in malarial coma, one of the severe manifestations of falciparum malaria. Cytoadherence is mediated by specific binding of variant parasite antigens, expressed on the surface of infected erythrocytes, to endothelial receptors including, ICAM-1, VCAM and CD36. In fatal cases of severe falciparum malaria with coma, blood vessels in the brain are characteristically congested with infected erythrocytes. Brain sections from a fatal case of knowlesi malaria, but without coma, were similarly congested with infected erythrocytes. The objective of this study was to determine the binding phenotype of Plasmodium knowlesi infected human erythrocytes to recombinant human ICAM-1, VCAM and CD36. METHODS: Five patients with PCR-confirmed P. knowlesi malaria were recruited into the study with consent between April and August 2010. Pre treatment venous blood was washed and cultured ex vivo to increase the proportion of schizont-infected erythrocytes. Cultured blood was seeded into Petri dishes with triplicate areas coated with ICAM-1, VCAM and CD36. Following incubation at 37 degrees C for one hour the dishes were washed and the number of infected erythrocytes bound/mm2 to PBS control areas and to recombinant human ICAM-1 VCAM and CD36 coated areas were recorded. Each assay was performed in duplicate. Assay performance was monitored with the Plasmodium falciparum clone HB3. RESULTS: Blood samples were cultured ex vivo for up to 14.5 h (mean 11.3 +/- 1.9 h) to increase the relative proportion of mature trophozoite and schizont-infected red blood cells to at least 50% (mean 65.8 +/- 17.51%). Three (60%) isolates bound significantly to ICAM-1 and VCAM, one (20%) isolate bound to VCAM and none of the five bound significantly to CD36. CONCLUSIONS: Plasmodium knowlesi infected erythrocytes from human subjects bind in a specific but variable manner to the inducible endothelial receptors ICAM-1 and VCAM. Binding to the constitutively expressed endothelial receptor CD36 was not detected. Further work will be required to define the pathological consequences of these interactions. PMID- 22305467 TI - Oseltamivir-resistant pandemic (H1N1) 2009 virus infections, United States, 2010 11. AB - During October 2010-July 2011, 1.0% of pandemic (H1N1) 2009 viruses in the United States were oseltamivir resistant, compared with 0.5% during the 2009-10 influenza season. Of resistant viruses from 2010-11 and 2009-10, 26% and 89%, respectively, were from persons exposed to oseltamivir before specimen collection. Findings suggest limited community transmission of oseltamivir resistant virus. PMID- 22305468 TI - Socioeconomic status and the development of depressive symptoms from childhood to adulthood: a longitudinal analysis across 27 years of follow-up in the Young Finns study. AB - We examined two alternative hypotheses on the association between low socioeconomic status (SES) and depressive symptoms: social causation and health selection. The latent growth curve (LGC) approach was used to examine trajectories of change in depressive symptoms over a period of 15 years in a dataset (the Young Finns study) consisting of a nationally representative sample of adolescents and young adults (n = 1613). Depressive symptoms were examined at four examination phases between 1992 and 2007. SES was measured as parental SES childhood (baseline of the study in 1980) and as the participants own SES in 2007 when the participants had reached adulthood and were between 30 and 45 years of age. The level of depressive symptoms was associated (r = -.14) with a slower decrease in symptoms during follow-up. Lower age, male gender, higher parental occupational grade but not parental income and lower negative emotionality in childhood were associated with a lower level of depressive symptoms. Higher age was also associated with a slower decrease in depressive symptoms. A lower level of depression and faster decrease in depressive symptoms were associated with a higher socioeconomic position in adulthood. A similar pattern was found in the relationship between the level of depression and income in adulthood. We concluded that the effect of childhood SES on depressive symptoms diminishes over time, but a higher level of, and especially faster decline of, depressive symptoms predicts the adulthood occupational SES gradient. PMID- 22305469 TI - Community health workers in Brazil's Unified Health System: a framework of their praxis and contributions to patient health behaviors. AB - Community health workers (CHWs) play a pivotal role in primary care, serving as liaisons between community members and medical providers. However, the growing reliance of health care systems worldwide on CHWs has outpaced research explaining their praxis - how they combine indigenous and technical knowledge, overcome challenges and impact patient outcomes. This paper thus articulates the CHW Praxis and Patient Health Behavior Framework. Such a framework is needed to advance research on CHW impact on patient outcomes and to advance CHW training. The project that originated this framework followed community-based participatory research principles. A team of U.S.-Brazil research partners, including CHWs, worked together from conceptualization of the study to dissemination of its findings. The framework is built on an integrated conceptual foundation including learning/teaching and individual behavior theories. The empirical base of the framework comprises in-depth interviews with 30 CHWs in Brazil's Unified Health System, Mesquita, Rio de Janeiro. Data collection for the project which originated this report occurred in 2008-10. Semi-structured questions examined how CHWs used their knowledge/skills; addressed personal and environmental challenges; and how they promoted patient health behaviors. This study advances an explanation of how CHWs use self-identified strategies--i.e., empathic communication and perseverance--to help patients engage in health behaviors. Grounded in our proposed framework, survey measures can be developed and used in predictive models testing the effects of CHW praxis on health behaviors. Training for CHWs can explicitly integrate indigenous and technical knowledge in order for CHWs to overcome contextual challenges and enhance service delivery. PMID- 22305470 TI - Welcome to the Twilight Zone: a forgotten early phase of human evolutionary studies. AB - The field of paleoanthropology arose out of a strange and unacknowledged early phase of development prior to about the 1930s. It is often assumed that a key pillar of the discipline, the unity of humankind--the notion that humans are clearly separated phylogenetically (genealogically) from other non-human primates -was widely accepted from the inception of paleoanthropology around 1860. However, a final consensus on this fundamental question only appeared later on in the 20th century. This paper will focus on two key areas of disagreement, which reveal the unsettled state of this question during this early period: the question of uncertainty with respect to the number, identity and boundary of primate species (including humans) which prevailed in the 18th, 19th and early 20th centuries; and the matter of uncertainty with respect to the nature of the phylogenetic relationships among the various human populations and the other primate species which prevailed between 1864 and 1931. Consideration of these matters reveals that the modern research structure that paleoanthropologists take for granted today is much more recent than believed. PMID- 22305471 TI - Richard Owen and the sea-serpent. AB - The well known naturalist, Richard Owen, had a career long engagement with monstrous creatures. In the 1830s he famously christened large fossil reptiles, Dinosauria. He investigated fossil marine reptiles as well as the giant moa. He also looked into the sea-serpents and sea monsters then drawing wide public attention. He actively collected letters and analyzed correspondence on the topic, consulted with the admiralty on reports of Royal Navy encounters and sightings, and commented in the public press. He concluded that such reports were based upon misidentifications of whales and other large marine mammals, and not run-ins with mythological creatures. His work on the sea-serpent shows that rather than discount the idea out of hand, a number of high profile naturalists were intrigued by monsters and attempted to understand what they were. His work is key to understanding the skepticism over monsters held by modern mainstream science. This skepticism opened the field to later amateur investigators. PMID- 22305473 TI - Endovascular repair of aortic isthmus coarctation with a self-expanding covered stent. AB - BACKGROUND: Coarctation is one of the most often seen congenital aortal defects. In the majority, diagnosis will be made in newborns. Endovascular repair is critical in children owing to their growth, but in adult patients, it is an interesting alternative. METHODS: A 31-year-old man presenting with hypertension of upper extremities and pulseless lower extremities was admitted to our hospital. Systolic blood pressure was 190 mm Hg, although a triple antihypertensive medication was administered. Computed tomographic angiography showed a nearly total occlusion of the aortic isthmus. Coarctation was treated by an endovascular approach with a self-expanding covered stent-graft (Medtronic Talent; Medtronic World Medical, Sunrise, FL) after predilatation with a Reliant balloon (Medtronic World Medical, Sunrise, FL). RESULTS: After a follow-up of 40 months, the patient is normotensive and antihypertensive medication could be reduced. Lower extremities showed normal pulses and normal ankle-brachial index. Computed tomographic scans showed unchanged stent-graft position, with constant slight waist. DISCUSSION: Endovascular repair of atresia or coarctation of the thoracic aorta is a minimal invasive debatable option. Not only reduction of blood pressure but also reduction of left ventricular mass and prolongation of life expectancy can be achieved by endovascular treatment. PMID- 22305474 TI - Unusual positional compression of the internal carotid artery causes carotid thrombosis and cerebral ischemia. AB - This article reports an unusual case of positional compression of internal carotid artery resulting in carotid thrombosis and stroke in a 37-year-old man. A patient was operated urgently for a free-floating thrombotic mass in the internal carotid artery. Open thrombectomy was performed in acute phase of stroke for prevention of the recapitulative cerebral thromboembolism. Hemiplegia completely disappeared within 7 months. PMID- 22305475 TI - Endovenous laser ablation: a review of mechanisms of action. AB - BACKGROUND: The aim of this article is to summarize and review the proposed theories on the laser action during endovenous ablation. METHODS: Laser mechanics and laser-tissue interaction are summarized from articles found in literature. Several theories, like the "steam bubble theory," the "direct contact theory," the "heat pipe," and "direct light energy absorption" are discussed. RESULTS: The laser light emitted intraluminally can be absorbed, scattered, or reflected. Reflection is negligible in the near-infrared spectrum. By combining absorption and scattering, the optical extinction of different wavelengths related to different biological tissues can be determined. The direct contact of the fiber tip and the vein wall may be a way of destroying the vein wall, but results in ulcerations and perforations of the vein wall. Avoiding this contact, and allowing direct light absorption into the vein wall, results in a more homogenous vein wall destruction. If the energy is mainly absorbed by the intraluminal blood, the laser fiber will act as a heat pipe. Histological studies show that a more circumferential vein wall destruction can be obtained when the vein is emptied of its intraluminal blood. The use of tumescent liquid reinforces spasm of the vein and protects the perivenous tissue. CONCLUSION: Several factors play an important role in the mechanism of endovenous laser ablation. Direct energy absorption by the vein wall is the most efficient mechanism. It is important to empty the vein of its intraluminal blood and to inject tumescent liquid around the vein. PMID- 22305476 TI - Therapeutic synthetic gene networks. AB - The field of synthetic biology is rapidly expanding and has over the past years evolved from the development of simple gene networks to complex treatment oriented circuits. The reprogramming of cell fate with open-loop or closed-loop synthetic control circuits along with biologically implemented logical functions have fostered applications spanning over a wide range of disciplines, including artificial insemination, personalized medicine and the treatment of cancer and metabolic disorders. In this review we describe several applications of interactive gene networks, a synthetic biology-based approach for future gene therapy, as well as the utilization of synthetic gene circuits as blueprints for the design of stimuli-responsive biohybrid materials. The recent progress in synthetic biology, including the rewiring of biosensing devices with the body's endogenous network as well as novel therapeutic approaches originating from interdisciplinary work, generates numerous opportunities for future biomedical applications. PMID- 22305477 TI - Evaluation of phenolic contents and antioxidant activity of various solvent extracts of Sonchus asper (L.) Hill. AB - BACKGROUND: Sonchus asper (SA) is traditionally used for the treatment of various ailments associated with liver, lungs and kidneys. This study was aimed to investigate the therapeutic potential of nonpolar (hexane, SAHE; ethyl acetate, SAEE and chloroform, SACE) and polar (methanol, SAME) crude extracts of the whole plant. METHODS: To achieve these goals, several parameters including free-radical (DPPH*, ABTS*+, H2O2 and *OH) scavenging, iron chelating activity, scavenging of superoxide radicals, total flavonoids and total phenolic content (TPC) were examined. RESULTS: The SA extracts presented a remarkable capacity to scavenge all the tested reactive species with IC50 values being found at the MUg / ml level. The SAME was shown to have the highest TPCs while lowest IC50 values for the DPPH*, ABTS*+ radical scavenging capacities and iron chelating scavenging efficiency, moreover, SAME had best activities in scavenging of superoxide radicals and hydrogen peroxide as well as potently scavenged the hydroxyl radicals. CONCLUSION: These results suggest the potential of S. asper as a medicine against free-radical-associated oxidative damage. PMID- 22305478 TI - Dispersible amyloid beta-protein oligomers, protofibrils, and fibrils represent diffusible but not soluble aggregates: their role in neurodegeneration in amyloid precursor protein (APP) transgenic mice. AB - Soluble amyloid beta-protein (Abeta) aggregates have been identified in the Alzheimer's disease (AD) brain. Dispersed Abeta aggregates in the brain parenchyma are different from soluble, membrane-associated and plaque-associated solid aggregates. They are in mixture with the extra- or intracellular fluid but can be separated from soluble proteins by ultracentrifugation. To clarify the role of dispersible Abeta aggregates for neurodegeneration we analyzed 2 different amyloid precursor protein (APP)-transgenic mouse models. APP23 mice overexpress human mutant APP with the Swedish mutation. APP51/16 mice express high levels of human wild type APP. Both mice develop Abeta-plaques. Dendritic degeneration, neuron loss, and loss of asymmetric synapses were seen in APP23 but not in APP51/16 mice. The soluble and dispersible fractions not separated from one another were received as supernatant after centrifugation of native forebrain homogenates at 14,000 * g. Subsequent ultracentrifugation separated the soluble, i.e., the supernatant, from the dispersible fraction, i.e., the resuspended pellet. The major biochemical difference between APP23 and APP51/16 mice was that APP23 mice exhibited higher levels of dispersible Abeta oligomers, protofibrils and fibrils precipitated with oligomer (A11) and protofibril/fibril (B10AP) specific antibodies than APP51/16 mice. These differences, rather than soluble Abeta and Abeta plaque pathology were associated with dendritic degeneration, neuron, and synapse loss in APP23 mice in comparison with APP51/16 mice. Immunoprecipitation of dispersible Abeta oligomers, protofibrils, and fibrils revealed that they were associated with APP C-terminal fragments (APP-CTFs). These results indicate that dispersible Abeta oligomers, protofibrils, and fibrils represent an important pool of Abeta aggregates in the brain that critically interact with membrane-associated APP C-terminal fragments. The concentration of dispersible Abeta aggregates, thereby, presumably determines its toxicity. PMID- 22305479 TI - Pandemic (H1N1) 2009 virus circulating in pigs, Guangxi, China. PMID- 22305462 TI - Apixaban versus aspirin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a predefined subgroup analysis from AVERROES, a randomised trial. AB - BACKGROUND: In the AVERROES study, apixaban, a novel factor Xa inhibitor, reduced the risk of stroke or systemic embolism in patients with atrial fibrillation who were at high risk of stroke but unsuitable for vitamin K antagonist therapy. We aimed to investigate whether the subgroup of patients with previous stroke or transient ischaemic attack (TIA) would show a greater benefit from apixaban compared with aspirin than would patients without previous cerebrovascular events. METHODS: In AVERROES, 5599 patients (mean age 70 years) with atrial fibrillation who were at increased risk of stroke and unsuitable for vitamin K antagonist therapy were randomly assigned to receive apixaban (5 mg twice daily) or aspirin (81-324 mg per day). The mean follow-up was 1.1 years. The primary efficacy outcome was stroke or systemic embolism; the primary safety outcome was major bleeding. Patients and investigators were masked to study treatment. In this prespecified subgroup analysis, we used Kaplan-Meier estimates of 1-year event risk and Cox proportional hazards regression models to compare the effects of apixaban in patients with and without previous stroke or TIA. AVERROES is registered at ClinicalTrials.gov, number NCT00496769. FINDINGS: In patients with previous stroke or TIA, ten events of stroke or systemic embolism occurred in the apixaban group (n=390, cumulative hazard 2.39% per year) compared with 33 in the aspirin group (n=374, 9.16% per year; hazard ratio [HR] 0.29, 95% CI 0.15-0.60). In those without previous stroke or TIA, 41 events occurred in the apixaban group (n=2417, 1.68% per year) compared with 80 in the aspirin group (n=2415, 3.06% per year; HR 0.51, 95% CI 0.35-0.74). The p value for interaction of the effects of aspirin and apixaban with previous cerebrovascular events was 0.17. Major bleeding was more frequent in patients with history of stroke or TIA than in patients without (HR 2.88, 95% CI 1.77-4.55) but risk of this event did not differ between treatment groups. INTERPRETATION: In patients with atrial fibrillation, apixaban is similarly effective whether or not patients have had a previous stroke or TIA. Given that those with previous stroke or TIA have a higher risk of stroke, the absolute benefits might be greater in these patients. FUNDING: Bristol-Myers Squibb and Pfizer. PMID- 22305480 TI - Transesterification of edible, non-edible and used cooking oils for biodiesel production using calcined layered double hydroxides as reusable base catalysts. AB - Fatty acid methyl esters (FAME) were produced from edible, non-edible and used cooking oils with different fatty acid contents by transesterification with methanol using calcined layered double hydroxides (LDHs) as solid base catalysts. Among the catalysts, calcined CaAl2-LDH (hydrocalumite) showed the highest activity with >90% yield of FAME using low methanol:oil molar ratio (<6:1) at 65 degrees C in 5 h. The activity of the catalyst was attributed to its high basicity as supported by Hammett studies and CO(2)-TPD measurements. The catalyst was successfully reused in up to four cycles. Some of the properties such as density, viscosity, neutralization number and glycerol content of the obtained biodiesel matched well with the standard DIN values. It is concluded that a scalable heterogeneously catalyzed process for production of biodiesel in high yields from a wide variety of triglyceride oils including used oils is possible using optimized conditions. PMID- 22305481 TI - Autothermal, single-stage, performic acid pretreatment of Miscanthus x giganteus for the rapid fractionation of its biomass components into a lignin/hemicellulose rich liquor and a cellulase-digestible pulp. AB - A novel approach to the performic acid pulping of biomass enables effective delignification and fractionation in a time frame not achieved heretofore. An autothermal decomposition reaction was triggered when 100mg/L Fe(2)(SO(4))(3) in 4.0 M NaOH was added to 5% or 7.5% H(2)O(2) in aqueous formic acid containing chipped Miscanthus x giganteus. Peroxy-decomposition resulted in pressures of 19 and 35 bar in the 5% and 7.5% peroxide liquors and reduced the lignin content in the resulting pulps to <6% within 140 and 30 min, respectively. Solubilised lignin was available for recovery from the liquor by subsequent dilution with water. Hemicellulose removal to the liquor was 68% and 89% for the 5% and 7.5% peroxide solutions. Crystalline cellulose yields were >99% and >95% and the rate of glucose release from cellulase digestion of the pulps in 24h was more than 20 fold that for the raw Miscanthus. PMID- 22305482 TI - Anti-malarial drugs: how effective are they against Plasmodium falciparum gametocytes? AB - BACKGROUND: Recent renewed emphasis on the eradication of malaria has highlighted the need for more tools with which to achieve this ambitious goal. One high priority area is the need to determine the gametocytocidal activity of both currently used anti-malarial drugs and those in the development pipeline. However, testing the activity of compounds against Plasmodium falciparum gametocytes is technically challenging both in vivo and in vitro. METHODS: Here the use of a simple robust assay to screen a panel of currently used and experimental anti-malarial drugs against mature P. falciparum gametocytes is described. RESULTS: Eight of 44 compounds tested reduced gametocyte viability by at least 50% and three showed IC50 values in nM range. CONCLUSIONS: There is a need to identify new compounds with activity against late stage gametocytes and the information provided by this in vitro assay is a valuable first step, which can guide future clinical studies. PMID- 22305483 TI - [Microbiology and public health: new challenges in surveillance and control of meningococcal disease]. PMID- 22305484 TI - Extended outbreak of cryptosporidiosis in a pediatric hospital, China. AB - Four Cryptosporidium spp. and 6 C. hominis subtypes were isolated from 102 of 6,284 patients in 3 pediatric hospitals in People's Republic of China. A cryptosporidiosis outbreak was identified retrospectively. The outbreak lasted >1 year and affected 51.4% of patients in 1 hospital ward, where 2 C. hominis subtypes with different virulence were found. PMID- 22305485 TI - Neuropeptide modulation of microcircuits. AB - Neuropeptides provide functional flexibility to microcircuits, their inputs and effectors by modulating presynaptic and postsynaptic properties and intrinsic currents. Recent studies have relied less on applied neuropeptide and more on their neural release. In rhythmically active microcircuits (central pattern generators, CPGs), recent studies show that neuropeptide modulation can enable particular activity patterns by organizing specific circuit motifs. Neuropeptides can also modify microcircuit output indirectly, by modulating circuit inputs. Recently elucidated consequences of neuropeptide modulation include changes in motor patterns and behavior, stabilization of rhythmic motor patterns and changes in CPG sensitivity to sensory input. One aspect of neuropeptide modulation that remains enigmatic is the presence of multiple peptide family members in the same nervous system and even the same neurons. PMID- 22305486 TI - [Parietal abscess with gallstones as a late complication of laparoscopic cholecystectomy]. PMID- 22305487 TI - Factors associated with depression treatment-response in an outpatient psychosomatic medicine practice: an exploratory retrospective study. AB - BACKGROUND AND OBJECTIVE: The author explored depression management outcomes in an outpatient psychosomatic medicine (PM) practice to identify factors associated with treatment response. METHODS: Medical records of 251 patients seen in the Mayo Clinic Rochester outpatient PM clinic who had patient health questionnaire-9 (PHQ-9) scores at the time of initial consultation and after consultation were reviewed. Comparisons of differences in pre- and post-consultation PHQ-9 scores were evaluated to identify patients with treatment response (score decreased > 50%). RESULTS: A total of 112 (44.6%) patients had initial PHQ-9 scores >= 5. Univariate comparisons revealed higher likelihood of response (25.9%) with lower average number of past antidepressant and antipsychotic trials, and reported good friend and family social support. After controlling for average number of medication trials, reported good friend support remained predictive of response (OR 3.4225, chi2 4.6743, P = 0.31); there was a trend for reported good family support to remain predictive (OR 2.7956; chi2 2.5933, P= 0.097). CONCLUSION: Though exploratory and underpowered to adequately assess all potential contributors, retrospective examination of factors associated with depression treatment-response in this outpatient PM practice emphasizes the relevance of perception of social support as markers of prognosis and outcome. PMID- 22305488 TI - A case of repeated brief psychotic episodes secondary to discontinuation of non prescription estrogen replacement therapy. PMID- 22305489 TI - Working memory deficits affect risky decision-making in methamphetamine users with attention-deficit/hyperactivity disorder. AB - Methamphetamine (MA) use and Attention-Deficit/Hyperactivity Disorder (ADHD) commonly co-occur and are independently associated with dysregulation of frontostriatal loops and risky decision-making; however, whether their comorbidity exacerbates risky decision-making is not known. This study evaluated 23 participants with histories of MA dependence and ADHD (MA+ADHD+), 25 subjects with MA dependence alone (MA+ADHD-), and 22 healthy adults (MA-ADHD-), who completed the Iowa Gambling Task (IGT) as part of a larger neuropsychiatric research evaluation. Results showed a significant interaction between ADHD, MA, and working memory, such that individuals with working memory deficits in the MA+ADHD+ cohort demonstrated the strongest propensity to select cards from "disadvantageous" versus "advantageous" decks on the IGT. This effect was not better explained by other psychiatric, substance use, neuromedical, or cognitive factors. Findings suggest that working memory deficits may moderate the expression of risky decision-making in MA users with ADHD. PMID- 22305490 TI - Association study between variants of AMP-activated protein kinase catalytic and regulatory subunit genes with antipsychotic-induced weight gain. AB - Weight gain and metabolic syndrome are the most common deleterious side effects following treatment with second generation antipsychotic drugs such as clozapine and olanzapine. However, the mechanisms underlying these negative effects of second generation antipsychotic drugs are not fully understood. In this study we investigate whether variants in the genes coding for the alpha-catalytic (PRKAA1, PRAKAA2) and the beta regulatory subunits (PRKAB1 and PRKAB2) of the cellular energy sensor AMP-activated protein kinase (AMPK) are associated with antipsychotic-induced weight gain. To accomplish this, ten polymorphisms in 208 schizophrenia or schizoaffective disorder patients treated with clozapine, haloperidol, risperidone or olanzapine for up to 14 weeks were analyzed. Significant association was observed between rs3766522 in PRKAB2 (AA vs. AT + TT; p = 0.022) and rs10789038 in PRKAA2 (GG + GA vs. AA, p = 0.023) with weight change (%) in patients of European ancestry following treatment with clozapine or olanzapine. Allelic association of the T-allele of rs3766522 (p = 0.019) and the G-allele of rs10789038 (p = 0.041) with weight change (%) was also observed. Analysis of raw weight gain revealed that carriers of the T-allele of rs3766522 (AT + TT, 4.3 kg +/- 3.7) gained more weight than the AA-genotype carriers (2.5 kg +/- 4.5, p = 0.042). Similarly, carriers of the G-allele of rs10789038 (GG + GA, 4.2 kg +/- 4.5) gained more weight than AA-homozygotes (1.5 kg +/- 2.9, p = 0.014) under antipsychotic treatment. In conclusion, we observed significant associations between polymorphisms in AMPK subunit genes and weight gain induced by clozapine and olanzapine. PMID- 22305491 TI - Development and characterization of highly polymorphic long TC repeat microsatellite markers for genetic analysis of peanut. AB - BACKGROUND: Peanut (Arachis hypogaea L.) is a crop of economic and social importance, mainly in tropical areas, and developing countries. Its molecular breeding has been hindered by a shortage of polymorphic genetic markers due to a very narrow genetic base. Microsatellites (SSRs) are markers of choice in peanut because they are co-dominant, highly transferrable between species and easily applicable in the allotetraploid genome. In spite of substantial effort over the last few years by a number of research groups, the number of SSRs that are polymorphic for A. hypogaea is still limiting for routine application, creating the demand for the discovery of more markers polymorphic within cultivated germplasm. FINDINGS: A plasmid genomic library enriched for TC/AG repeats was constructed and 1401 clones sequenced. From the sequences obtained 146 primer pairs flanking mostly TC microsatellites were developed. The average number of repeat motifs amplified was 23. These 146 markers were characterized on 22 genotypes of cultivated peanut. In total 78 of the markers were polymorphic within cultivated germplasm. Most of those 78 markers were highly informative with an average of 5.4 alleles per locus being amplified. Average gene diversity index (GD) was 0.6, and 66 markers showed a GD of more than 0.5. Genetic relationship analysis was performed and corroborated the current taxonomical classification of A. hypogaea subspecies and varieties. CONCLUSIONS: The microsatellite markers described here are a useful resource for genetics and genomics in Arachis. In particular, the 66 markers that are highly polymorphic in cultivated peanut are a significant step towards routine genetic mapping and marker-assisted selection for the crop. PMID- 22305492 TI - Cutaneous melioidosis in adolescent returning from Guadeloupe. PMID- 22305493 TI - Discovery of a new class of ghrelin receptor antagonists. AB - A series of benzodiazepine antagonists of the human ghrelin receptor GHSR1a were synthesized and their antagonism and metabolic stability were evaluated. The potency of these analogs was determined using a functional aequorin (Euroscreen) luminescent assay measuring the intracellular Ca(2+) concentration, and their metabolic stability was measured using an in vitro rat and human S9 hepatocyte assay. These efforts led to the discovery of a potent ghrelin antagonist with good rat pharmacokinetic properties. PMID- 22305494 TI - Cytotoxic terpenoids from Juglans sinensis leaves and twigs. AB - Bioassay-guided fractionation of an 80% MeOH extract of Juglan sinensis leaves and twigs has resulted in the isolation of three new triterpenes (1-3) and two new sesquiterpenes (4-5) along with two known sesquiterpenes (6-7). The new compounds were determined to be 3beta, 11alpha, 19alpha, 24, 30-pentahydroxy 20beta, 28-epoxy-28beta-methoxy-ursane (1), 1alpha, 3beta-dihydroxy-olean-18-ene (2), 2alpha, 3alpha, 23-trihydroxy-urs-12-en-28-oic acid 28-O-beta-d glucopyranoside (3), (4S, 5S, 7R, 8R, 14R)-8, 11-dihydroxy-2, 4-cyclo-eudesmane (4), 15-hydroxy-alpha-eudesmol-11-O-beta-d-glucopyranoside (5), by spectroscopic analysis. The cytotoxicity of compounds (1-7) against four cancer cell lines such as B16F10, Hep-2, MCF-7 and U87-MG was evaluated. Compounds 1, 2, 6 and 7 showed potent cytotoxicity against all of four cancer cell lines, respectively. PMID- 22305496 TI - Systemic inflammatory response syndrome in patients with liver cirrhosis. AB - BACKGROUND AND STUDY AIMS: Patients with liver cirrhosis present an increased susceptibility to the systemic inflammatory response syndrome (SIRS), which is considered the cause of hospital admission in about 10% of patients and is present in about 40% of those admitted for ongoing complications. We tried to assess the prevalence of the SIRS with the possible effects on the course of the disease during hospital stay. PATIENTS AND METHODS: Two hundred and three patients with liver cirrhosis were examined and investigated with close monitoring during hospital stay. The main clinical endpoints were death and the development of portal hypertension-related complications. RESULTS: Eighty-one patients met the criteria of SIRS (39.9%). We found significant correlations between SIRS and jaundice (p=0.005), bacterial infection (p=0.008), white blood cell count (p<0.001), low haemoglobin concentration (p=0.004), high serum creatinine levels (p<0.001), high alanine aminotransferase levels (p<0.001), serum bilirubin levels (p<0.001), international normalised ratio (p<0.001), serum albumin levels (p=0.033), high Child-Pugh score (p<0.001). During the follow-up period, 26 patients died (12.8%), 15 developed portal hypertension-related bleeding (7.3%), 30 developed hepatic encephalopathy (14.7%), and 9 developed hepatorenal syndrome type-1 (4.4%). SIRS showed significant correlations both to death (p<0.001) and to portal hypertension-related complications (p<0.001). CONCLUSION: The systemic inflammatory response syndrome occurs in patients with advanced cirrhosis and is associated with a bad prognosis. PMID- 22305495 TI - Protein tyrosine phosphatase receptor delta acts as a neuroblastoma tumor suppressor by destabilizing the aurora kinase A oncogene. AB - BACKGROUND: Protein tyrosine phosphatase receptor delta (PTPRD) is a member of a large family of protein tyrosine phosphatases which negatively regulate tyrosine phosphorylation. Neuroblastoma is a major childhood cancer arising from precursor cells of the sympathetic nervous system which is known to acquire deletions and alterations in the expression patterns of PTPRD, indicating a potential tumor suppressor function for this gene. The molecular mechanism, however, by which PTPRD renders a tumor suppressor effect in neuroblastoma is unknown. RESULTS: As a molecular mechanism, we demonstrate that PTPRD interacts with aurora kinase A (AURKA), an oncogenic protein that is over-expressed in multiple forms of cancer, including neuroblastoma. Ectopic up-regulation of PTPRD in neuroblastoma dephosphorylates tyrosine residues in AURKA resulting in a destabilization of this protein culminating in interfering with one of AURKA's primary functions in neuroblastoma, the stabilization of MYCN protein, the gene of which is amplified in approximately 25 to 30% of high risk neuroblastoma. CONCLUSIONS: PTPRD has a tumor suppressor function in neuroblastoma through AURKA dephosphorylation and destabilization and a downstream destabilization of MYCN protein, representing a novel mechanism for the function of PTPRD in neuroblastoma. PMID- 22305497 TI - Clinico-laboratory study on children with auto-immune hepatitis in Upper Egypt. AB - BACKGROUND AND STUDY AIMS: Auto-immune hepatitis (AIH) in children is a rare chronic progressive liver disorder. It is characterised serologically by high aminotransferase levels, elevated immunoglobulin G (IgG) and the presence of autoantibodies. AIH is divided into two types according to the autoantibody profile. This study aims to assess frequency, clinical manifestations, biochemical features and outcome of AIH in children attending Assuit University Hospitals in Upper Egypt with acute icteric hepatitis and seronegative viral markers (anti-hepatitis A virus (HAV) IgM, HbsAg, anti-hepatitis C virus (anti HCV) Ab). PATIENTS AND METHODS: The study includes 34 children with AIH, diagnosed on the basis of the International Scoring Criteria of Auto-immune Hepatitis, recruited from Assuit University Hospitals, during the period from January 2005 to December 2009. All patients received prednisolone 2mgkg(-1)day( 1). Follow-up was done for 1year. RESULTS: Among 34 children diagnosed as AIH, 24 were females (70.5%) and 10 were males (29.5%). Jaundice represented the most consistent finding in all patients. According to the autoantibody profile, 25 children were classified as type 1 and nine children were classified as type 2. Corticosteroid therapy was started. Complete remission was observed in 67.6% of patients and partial remission in 17.6%. There was no significant statistical difference in clinical and biochemical features of AIH in patients regarding the response to treatment. Mild side effects of steroid therapy were encountered in 48.2% of patients. After complete withdrawal of corticosteroids, six patients (20.7%) developed relapse. CONCLUSION: AIH type 1 was the main form of AIH in children referred to Assiut University Hospitals. Girls were more affected than boys. AIH type 1 exhibited a more active, ongoing immunologic process. Steroid alone can be used successfully in most cases. Children with AIH type 2 had a higher frequency of relapse after corticosteroid withdrawal. Further studies on a larger number of cases and long-term follow-up are recommended. PMID- 22305498 TI - Portal hypertensive colopathy and haematochezia in cirrhotic patients: an endoscopic study. AB - BACKGROUND AND STUDY AIMS: In patients with liver cirrhosis, portal hypertensive colopathy (PHC) and anorectal varices (ARVs) are thought to cause lower gastrointestinal (GI) bleeding. In the present work, we studied the diagnostic yield of colonoscopy in cirrhotic patients and haematochezia. PATIENTS AND METHODS: The current study was conducted on 77 consecutive cirrhotic patients who underwent colonoscopy at Mansoura Emergency Hospital, Egypt, between May 2007 and May 2011. Following rapid evaluation and adequate resuscitation, a thorough history was obtained with complete physical examination including digital rectal examination and routine laboratory investigations. Colonoscopic evaluation was performed for the included patients by recording endoscopic abnormalities and obtaining biopsies from lesions. RESULTS: There was no significant difference between the PHC-positive group when compared with the PHC-negative group regarding patients' age, sex, severity of haematochezia, positive family history and the history of intake of non-steroidal anti-inflammatory drugs (NSAIDs). Significant difference was noted regarding the Child-Pugh class (p<0.05), history of splenectomy (p<0.05), prior history of endoscopic sclerotherapy (EST) or endoscopic variceal ligation (EVL) (p<0.05), prior history of upper gut bleeding (p<0.05), the presence of gastric varices (GVs) (p<0.05), presence of portal hypertensive gastropathy (PHG) (p<0.05), presence of haemorrhoids (p<0.05) and rectal varices (<0.05) and therapy with beta-blockers (p<0.05). Regarding the laboratory parameters, the platelet count only was markedly reduced in the PHC positive group (p<0.05). All the PHC-related sources of bleeding (7/32 cases (21.87%)) were successfully managed with argon plasma coagulation. Regarding the laboratory parameters, the platelet count only was markedly reduced in the PHC positive group (p<0.05). All the PHC-related sources of bleeding (7/32 cases (21.87%)) were successfully managed with argon plasma coagulation. CONCLUSION: Our data revealed that it is not only PHC which is involved in haematochezia in cirrhotic patients despite the significant association. Instead, a high prevalence of inflammatory lesions came on the top of the list. Complete colonoscopy is highly advocated to detect probable proximal neoplastic lesions. PMID- 22305499 TI - Comparison of Doppler-guided haemorrhoidal artery ligation without mucopexy and rubber band ligation for haemorrhoids. AB - BACKGROUND AND STUDY AIMS: Recurrences after Doppler-guided haemorrhoidal artery ligation (DG-HAL) tend to occur in patients with concurrent mucosal prolapse. We retrospectively compared the results of DG-HAL and rubber band ligation (RBL) for the treatment of haemorrhoidal disease. PATIENTS AND METHODS: From 2005 to 2009, all patients who underwent either a DG-HAL procedure or RBL were selected. Follow up was done by telephone using a standardised questionnaire survey to assess patient satisfaction and complaints. When recurrent disease was suspected, patients revisited the clinic for further examination and treatment. RESULTS: A total of 239 DG-HAL patients and 47 RBL patients were analysed. Sixty-seven percent in the DG-HAL group and 79% in the RBL group had an improvement in symptoms after one treatment (p=0.22). Forty-six DG-HAL patients (19%) needed a second procedure versus three patients (6%) in the RBL group (p<0.05). Cox regression analysis showed a significant difference in disease recurrence in favour of RBL (hazard ratio (HR) 3.71, 95% confidence interval (CI) 1.13-12.2). Patients in the DG-HAL group with recurrent haemorrhoids had a higher incidence of mucosal prolapse. CONCLUSION: DG-HAL seems very effective in treating lower grade haemorrhoids. In more advanced disease, recurrence occurs due to persisting mucosal prolapse. RBL seems much more effective in reducing the prolapse and the chance of recurrence. PMID- 22305500 TI - The pathogenic role of different Blastocystis hominis genotypes isolated from patients with irritable bowel syndrome. AB - BACKGROUND AND STUDY AIMS: The pathogenic role of Blastocystis hominis is still regarded by some as controversial. Studies have been in progress for years to evaluate the role of blastocystosis in irritable bowel syndrome (IBS) and demonstrated that faecal carriage of B. hominis was frequent in these patients. This study attempted to distinguish different genotypes of B. hominis isolates obtained from patients with IBS and to evaluate their pathogenic potentials. PATIENTS AND METHODS: One hundred subjects (51 patients with IBS and 49 asymptomatic infected subjects) harbouring B. hominis were investigated by a direct smear examination and in vitro culture of stool samples followed by genotyping of B. hominis by PCR using STS primers. Sigmoidoscopy was done in all subjects and biopsies were taken and subjected to histopathologic examination. RESULTS: Genotyping proved that only four genotypes of B. hominis were identified. In patients with IBS, genotypes III, I, and IV were detected (28, 15 and 14 isolates, respectively). On the other hand, genotypes III, IV, and II were identified in asymptomatic infected individuals (21, 19 and 13 isolates, respectively). The degrees of chronic inflammatory changes in sigmoidoscopic biopsies caused by B. hominis genotypes among IBS patients revealed that severe inflammation was present mainly in patients harboring genotype I isolates (4/15) (26.66%), while genotype III caused severe inflammation only in 9.09%. Genotype II isolates were not detected in IBS cases. Asymptomatic infected individuals harboring genotypes II, III and IV exhibited mild to moderate inflammatory changes. Genotype I isolates were not detected in asymptomatic infected group. The correlation between different B. hominis genotypes and degree of inflammation was statistically insignificant. CONCLUSION: Genotype I was the most pathogenic genotype of B. hominis isolates in patients with IBS while genotype II was not detected among those patients. Also, our results suggest the presence of pathogenic and non-pathogenic strains among genotypes III and IV. PMID- 22305501 TI - Erosive gastritis mimicking watermelon stomach in a child. AB - Watermelon stomach is the description usually given to the endoscopic appearance of gastric antral vascular ectasia. The classical histopathological features of gastric antral vascular ectasia include; hyperplasia of the surface epithelium and the fibromuscular layer of the lamina propria associated with the presence of dilated submucosal venous channels and thrombosed capillaries. This condition can be associated with liver cirrhosis, chronic renal failure and autoimmune disorders. Herein, we report the watermelon endoscopic appearance of the gastric mucosa in a 12-year-old Saudi girl with erosive gastritis. PMID- 22305502 TI - Unique endoscopic findings in lymphocytic colitis. PMID- 22305505 TI - Pandemic (H1N1) 2009 in captive cheetah. AB - We describe virus isolation, full genome sequence analysis, and clinical pathology in ferrets experimentally inoculated with pandemic (H1N1) 2009 virus recovered from a clinically ill captive cheetah that had minimal human contact. Evidence of reverse zoonotic transmission by fomites underscores the substantial animal and human health implications of this virus. PMID- 22305506 TI - Cardiac biomarkers, mortality, and post-traumatic stress disorder in military veterans. AB - Post-traumatic stress disorder (PTSD) is gaining increasing recognition as a risk factor for morbidity and mortality. The aim of this study was to examine the impact of PTSD and abnormal cardiovascular biomarkers on mortality in military veterans. Eight hundred ninety-one patients presenting for routine echocardiography were enrolled. Baseline clinical data and serum samples for biomarker measurement were obtained and echocardiography was performed at the time of enrollment. Patients were followed for up to 7.5 years for the end point of all-cause mortality. Ninety-one patients had PTSD at the time of enrollment. There were 33 deaths in patients with PTSD and 221 deaths in those without PTSD. Patients with PTSD had a trend toward worse survival on Kaplan-Meier analysis (p = 0.057). Among patients with elevated B-type natriuretic peptide (>60 pg/ml), those with PTSD had significantly increased mortality (p = 0.024). Among patients with PTSD, midregional proadrenomedullin (MR-proADM), creatinine, and C-terminal proendothelin-1 were significant univariate predictors of mortality (p = 0.006, p = 0.024, and p = 0.003, respectively). In a multivariate model, PTSD, B-type natriuretic peptide, and MR-proADM were independent predictors of mortality. In patients with PTSD, MR-proADM was a significant independent predictor of mortality after adjusting for B-type natriuretic peptide, cardiovascular risk factors, cancer, and sleep apnea. Adding MR-proADM to clinical predictors of mortality increased the C-statistic from 0.572 to 0.697 (p = 0.007). In conclusion, this study demonstrates an association among PTSD, abnormal cardiac biomarker levels, and increased mortality. PMID- 22305507 TI - Giant laterally spreading tumors of the duodenum: endoscopic resection outcomes, limitations, and caveats. AB - BACKGROUND: Giant hemicircumferential and greater nonampullary duodenal adenomas or laterally spreading tumors (LSTs) may be amenable to safe endoscopic resection, but little data exists on outcomes or risk stratification. DESIGN: We interrogated a prospectively maintained database of all patients who underwent endoscopic resection between January 2008 and November 2010. The resection technique was standardized. Major complications were defined as perforation, bleeding requiring readmission with hemoglobin drop of more than 20 g/L, or other substantial deviations from the usual clinical course. Outcomes were analyzed in 2 groups: giant lesions (>30 mm) and conventional duodenal polyps (<30 mm in diameter). Statistical evaluation was performed by using a chi(2) test. RESULTS: A total of 50 nonampullary duodenal polyps and LSTs were resected from 46 patients (23 men, mean age 59.4 years, range 35-83 years). Nineteen were giant hemicircumferential and greater LSTs (mean size 40.5 mm, range 30-80 mm), and 31 were less than 30 mm in diameter (mean size 14.5 mm, range 5-25 mm). Intraprocedural bleeding occurred more frequently in giant lesions (57.8% vs 19.3%, P = .005) and was treated with a combination of soft coagulation and endoscopic clips with hemostasis achieved in all cases. Major complications, mostly bleeding related, occurred in 5 patients (26.3%) with giant lesions and 1 patient (3.2%) with a smaller lesion (P = .014). There were no deaths. LIMITATION: Retrospective observational study in a tertiary center. CONCLUSIONS: Endoscopic resection of giant nonampullary duodenal LSTs is a successful treatment. However, it is hazardous and associated with significantly higher complication rates, primarily bleeding, when compared with conventional duodenal polypectomy. Safer and more effective hemostatic tools are required in this high risk location. PMID- 22305508 TI - Esophageal leiomyomatosis presenting as achalasia diagnosed by high-resolution manometry and endoscopic core biopsy. PMID- 22305509 TI - Biopsy and implantation of the seminal vesicles. AB - PURPOSE: To describe the technique and outcomes of seminal vesicle biopsy (SVB) and permanent implantation in patients with T3b prostate cancer. METHODS AND MATERIALS: Intermediate- and high-risk prostate cancer patients who elected brachytherapy as their treatment of choice were offered SVB for either Gleason score >=7, prostate-specific antigen levels >10ng/mL, or clinical stage >=T2b. Three cores were taken from both seminal vesicles at the base of the prostate using transrectal ultrasound. Patients with a positive SVB and either a negative pelvic lymph node dissection or pelvic computerized tomogram were treated with a combination of a partial implant followed by 45Gy of external beam irradiation therapy. During the seed implant, sources were positioned in the anterior wall of the seminal vesicles using intraoperative dosimetry to guide placement. Biochemical freedom from failure was determined using a definition of >0.2ng/mL. Survival was measured using the Kaplan-Meier and Cox proportions projections. RESULTS: Of 526 patients who underwent SVB, 52 (9.9%) were positive for prostate cancer invasion. Clinical stage, prostate-specific antigen levels, and Gleason score were all predictive of a positive SVB (p<0.001). The 10-year biochemical freedom from failure was 64%. Cox regression demonstrated Gleason score (p=0.044) and biologic effective dose (p=0.013) as significant. CONCLUSIONS: Patients with pathologically confirmed seminal vesicle involvement of prostate cancer can be successfully identified and managed by a combined approach of permanent seed implantation to the prostate and seminal vesicles followed by external beam irradiation therapy. SVB should be encouraged in men with high-risk prostate cancer and aggressively treated when encountered. PMID- 22305511 TI - Is the prognosis of stage 4s neuroblastoma in patients 12 months of age and older really excellent? AB - PURPOSE: In the International Neuroblastoma Risk Group (INRG) classification system, stage 4s was changed into stage MS in children less than 18 months of age. Stage MS is defined as a metastatic disease with skin, liver and bone marrow, similar to INSS stage 4s. To evaluate the outcome of stage 4s cases in patients 12 months of age and over and to determine the appropriate treatment strategy. METHOD: We performed a retrospective review of 3834 patients registered with the Japanese Society of Pediatric Oncology and Japanese Society of Pediatric Surgeons between 1980 and 1998. RESULTS: The rates of stage 4s patients were 10.7%, 6.3% and 3.3% in patients of >= 11 months of age, from >= 12 to <= 17 months of age, >= 18 months of age, respectively. The 5 year event-free survival rates were 89.4%, 100% and 53.1%, respectively. The rates of MYCN amplification and unfavourable histology were smaller in stage 4s groups than stage 4 groups in all ages. CONCLUSION: In the children 12 months of age and older, stage 4s cases are markedly different from stage 4 cases in regard to the clinical features and prognosis. The prognosis of stage 4s cases from >= 12 to <= 17months of age is excellent. The concept of stage MS appears to be appropriate. PMID- 22305512 TI - Stop and go strategy for opioid switching requires flexibility. PMID- 22305513 TI - Sex-specific differences in the relationship between genetic susceptibility, T cell DNA demethylation and lupus flare severity. AB - Lupus is less common in men than women, and the reason is incompletely understood. Current evidence indicates that lupus flares when genetically predisposed individuals encounter environmental agents that trigger the disease, and that the environmental contribution is mediated at least in part by T cell DNA demethylation. We hypothesized that lupus disease activity is directly related to total genetic risk and inversely related to T cell DNA methylation levels in each patient. Since women are predisposed to lupus in part because of their second X chromosome, we also hypothesized that men would require a greater genetic risk, a greater degree of autosomal T cell DNA demethylation, or both, to achieve a lupus flare equal in severity to women. Genetic risk was determined by genotyping men and women with lupus across 32 confirmed lupus susceptibility loci. The methylation status of two autosomal genes known to demethylate in T cells in proportion to disease activity, KIR2DL4 (KIR) and PRF1, was measured by bisulfite sequencing. Lupus disease activity was determined by the SLEDAI. Interactions between genetic score, T cell DNA demethylation, and the SLEDAI score were compared between the men and women by regression analysis. Combining the degree of DNA demethylation with the genetic risk score for each patient demonstrated that the (genetic risk)/(DNA methylation) ratio increased directly with disease activity in both men and women with lupus. Importantly, men required a greater (genetic risk)/(DNA methylation) ratio to achieve a SLEDAI score equivalent to women (P = 0.010 for KIR and P = 0.0054 for PRF1). This difference was not explained by a difference in the genetic risk or T cell DNA demethylation alone, suggesting a genetic-epigenetic interaction. These results suggest that genetic risk and T cell DNA demethylation interact in lupus patients to influence the severity of lupus flares, and that men require a higher genetic risk and/or greater degree of T cell DNA demethylation to achieve a lupus flare equal in severity to women. PMID- 22305514 TI - [Integrated delivery systems and other examples of collaboration among providers. SESPAS report, 2012]. AB - Because of the steady increase in healthcare complexity, due to high specialization and the involvement of a number of services, as well as the increase in patients with chronic diseases and pluripathology, coordination has become a high-priority need in healthcare systems. The distinct regional services that comprise the decentralized Spanish National Health System have developed a number of experiences to improve collaboration among the providers involved in the healthcare process. The present article aims to analyze the experiences with integrated healthcare providers in Catalonia and the Basque Country and the chronic diseases programs of the latter. In Catalonia, which promoted the purchaser-provider split and maintained diversity in providers' ownership, organizations were slowly created that manage the provision of the healthcare continuum, known as integrated healthcare organizations (IHO). These organizations have evolved and, despite some common characteristics, they also show some differences, such as the emphasis on formal instruments or on coordination mechanisms and organic structures. This is also reflected in their results regarding culture and perceived coordination across the organization. In the Basque Country, in addition to the establishment of an IHO, a variety of integration experiences have been developed to improve the care of chronic diseases. PMID- 22305515 TI - [Financial incentives in improving healthcare quality. SESPAS Report 2012]. AB - We address the contribution of financial incentives linked to pay for performance (P4P) to improving the quality of care. The situation of P4P is analyzed internationally and in the distinct health services in Spain. The participation of P4P in wage compensation and the effects of the current economic crisis on these incentives is discussed. We review the results of recent studies to clarify the role of these incentive models and assess possible orientations and new proposals. PMID- 22305516 TI - [Diffuse brain involvement in paediatrics: magnetic resonance findings]. AB - Posterior fossa involvement, which may be focal or diffuse, is an uncommon finding in paediatric patients. Acute cerebellitis is the first condition to be suspected among the diffuse forms, and ataxia is the most characteristic symptom. This condition is occasionally difficult to diagnose clinically, thus imaging tests play an important role in this. However, there are other rare conditions which may be clinically and radiologically similar to acute cerebellitis and which should be taken into account when making a differential diagnosis. The aim of this article is to present five diseases with diffuse brain involvement in paediatric patients and describe how they show up in MR imaging. PMID- 22305517 TI - Associations of ESR2 AluI (G/A) polymorphism with ischemic stroke in Caucasians. AB - Raising interest towards genes implicates the effect of estrogen receptor-alpha (ESR1) gene on cerebrovascular disease, but data are lacking regarding the effect of estrogen receptor-beta (ESR2) gene. We assessed the hypothesis that AluI (G/A) polymorphism of the ESR2 gene (rs 4986938) is associated with ischemic stroke in a Caucasian population. Four hundred twenty four consecutive stroke patients and 430 age and gender-matched controls were enrolled in three stroke centers in Greece over one-year period. Patients and controls were compared in regard to the prevalence of the aforementioned polymorphism. No association was found between variations in the ESR2 gene and risk of stroke or stroke subtype in men and women. Of note, a gender-specific association of G allele with the onset of stroke at a younger age in male patients was found (63.68 +/- 12.687 years in G allele (GG+AG) carriers vs. 68.95 +/- 10.757 years in non-carriers (AA), p=0.008). Further population independent studies are needed to establish the role of ESR2 gene polymorphisms in relation to ischemic stroke in both genders. Such studies could lead to ERbeta agonists being validated in individuals with certain genotypes and/or alleles towards the development of efficient strategies to preventing ischemic stroke in both men and women. PMID- 22305518 TI - Geographic distribution of endemic fungal infections among older persons, United States. PMID- 22305519 TI - Linking mitochondrial bioenergetics to insulin resistance via redox biology. AB - Chronic overnutrition and physical inactivity are major risk factors for insulin resistance and type 2 diabetes. Recent research indicates that overnutrition generates an increase in hydrogen peroxide (H(2)O(2)) emission from mitochondria, serving as a release valve to relieve the reducing pressure created by fuel overload, as well as a primary signal that ultimately decreases insulin sensitivity. H(2)O(2) is a major input to cellular redox circuits that link to cysteine residues throughout the entire proteome to regulate cell function. Here we review the principles of mitochondrial bioenergetics and redox systems biology and offer new insight into how H(2)O(2) emission may be linked via redox biology to the etiology of insulin resistance. PMID- 22305520 TI - The interactions between the circadian clock and primary metabolism. AB - Primary metabolism in plants is tightly regulated by environmental factors such as light and nutrient availability at multiple levels. The circadian clock is a self-sustained endogenous oscillator that enables organisms to predict daily and seasonal changes. The regulation of primary metabolism by the circadian clock has been proposed to explain the importance of circadian rhythms in plant growth and survival. Recent transcriptomic and metabolomic analyses indicate a wide spread circadian regulation of different metabolic processes. We review evidence of circadian regulation of pathways in primary metabolism, discuss the challenges faced for discerning the mechanisms regulating circadian metabolic oscillations and present recent evidence of regulation of the circadian clock by metabolites. PMID- 22305521 TI - Sensing nutrient and energy status by SnRK1 and TOR kinases. AB - The perception of nutrient and energy levels inside and outside the cell is crucial to adjust growth and metabolism to available resources. The signaling pathways centered on the conserved TOR and SnRK1/Snf1/AMPK kinases have crucial and numerous roles in nutrient and energy sensing and in translating this information into metabolic and developmental adaptations. In plants evidence is mounting that, like in other eukaryotes, these signaling pathways have pivotal and antagonistic roles in connecting external or intracellular cues to many biological processes, including ribosome biogenesis, regulation of translation, cell division, accumulation of reserves and autophagy. Data on the plant TOR pathway have been hitherto rather scarce but recent findings have shed new light on its roles in plants. Moreover, the distinctive energy metabolism of photosynthetic organisms may reveal new features of these ancestral eukaryotic signaling elements. PMID- 22305522 TI - Redundancy and rewiring of genetic networks following genome-wide duplication events. AB - Polyploidy or whole-genome duplication is a frequent phenomenon within the plant kingdom and has been associated with the occurrence of evolutionary novelty and increase in biological complexity. Because genome-wide duplication events duplicate whole molecular networks it is of interest to investigate how these networks evolve subsequent to such events. Although genome duplications are generally followed by massive gene loss, at least part of the network is usually retained in duplicate and can rewire to execute novel functions. Alternatively, the network can remain largely redundant and as such confer robustness against mutations. The increasing availability of high-throughput data makes it possible to study evolution following whole genome duplication events at the network level. Here we discuss how the use of 'omics' data in network analysis can provide novel insights on network redundancy and rewiring and conclude with some directions for future research. PMID- 22305523 TI - Paroxysmal neuromyotonia: a new sporadic channelopathy. AB - Neuromyotonia is a heterogeneous group of genetic and autoimmune channelopathies resulting in hyperexcitability of peripheral nerves. We report an unusual case of neuromyotonia, which to our knowledge has not been previously described. The patient developed intermittent attacks of severe painful muscle stiffness accompanied by sweating, myokymia and raised serum creatine kinase. Genetic analysis of KCNA1, KCNQ2 and SCN4A genes did not identify pathogenic mutation. Serum voltage-gated potassium channel antibody was also negative. He was successfully treated with acetazolamide and carbamazepine. This appears to be a new neuromuscular disease, "paroxysmal neuromyotonia", the etiology of which is still unknown. PMID- 22305524 TI - Economic growth and obesity: an interesting relationship with world-wide implications. AB - The prosperity of a country, commonly measured in terms of its annual per capita Gross Domestic Product (GDP), has different relationships with population levels of body weight and happiness, as well as environmental impacts such as carbon emissions. The aim of this study was to examine these relationships and to try to find a level of GDP, which provides for sustainable economic activity, optimal happiness and healthy levels of mean body mass index (BMI). Spline regression analyses were conducted using national indices from 175 countries: GDP, adult BMI, mean happiness scores, and carbon footprint per capita for the year 2007. Results showed that GDP was positively related to BMI and happiness up to ~$US3000 and ~$5000 per capita respectively, with no significant relationships beyond these levels. GDP was also positively related to CO(2) emissions with a recognised sustainable carbon footprint of less than 5 tonnes per capita occurring at a GDP of <$US15,000. These findings show that a GDP between $US5 and $15,000 is associated with greater population happiness and environmental stability. A mean BMI of 21-23 kg/m(2), which minimises the prevalence of underweight and overweight in the population then helps to define an ideal position in relation to growth, which few countries appear to have obtained. Within a group of wealthy countries (GDP>$US30,000), those with lower income inequalities and more regulated (less liberal) market systems had lower mean BMIs. PMID- 22305525 TI - Shuni virus as cause of neurologic disease in horses. AB - To determine which agents cause neurologic disease in horses, we conducted reverse transcription PCR on isolates from of a horse with encephalitis and 111 other horses with acute disease. Shuni virus was found in 7 horses, 5 of which had neurologic signs. Testing for lesser known viruses should be considered for horses with unexplained illness. PMID- 22305526 TI - RAD51 haploinsufficiency causes congenital mirror movements in humans. AB - Congenital mirror movements (CMM) are characterized by involuntary movements of one side of the body that mirror intentional movements on the opposite side. CMM reflect dysfunctions and structural abnormalities of the motor network and are mainly inherited in an autosomal-dominant fashion. Recently, heterozygous mutations in DCC, the gene encoding the receptor for netrin 1 and involved in the guidance of developing axons toward the midline, have been identified but CMM are genetically heterogeneous. By combining genome-wide linkage analysis and exome sequencing, we identified heterozygous mutations introducing premature termination codons in RAD51 in two families with CMM. RAD51 mRNA was significantly downregulated in individuals with CMM resulting from the degradation of the mutated mRNA by nonsense-mediated decay. RAD51 was specifically present in the developing mouse cortex and, more particularly, in a subpopulation of corticospinal axons at the pyramidal decussation. The identification of mutations in RAD51, known for its key role in the repair of DNA double-strand breaks through homologous recombination, in individuals with CMM reveals a totally unexpected role of RAD51 in neurodevelopment. These findings open a new field of investigation for researchers attempting to unravel the molecular pathways underlying bimanual motor control in humans. PMID- 22305527 TI - DDOST mutations identified by whole-exome sequencing are implicated in congenital disorders of glycosylation. AB - Congenital disorders of glycosylation (CDG) are inherited autosomal-recessive diseases that impair N-glycosylation. Approximately 20% of patients do not survive beyond the age of 5 years old as a result of widespread organ dysfunction. Although most patients receive a CDG diagnosis based on abnormal glycosylation of transferrin, this test cannot provide a genetic diagnosis; indeed, many patients with abnormal transferrin do not have mutations in any known CDG genes. Here, we combined biochemical analysis with whole-exome sequencing (WES) to identify the genetic defect in an untyped CDG patient, and we found a 22 bp deletion and a missense mutation in DDOST, whose product is a component of the oligosaccharyltransferase complex that transfers the glycan chain from a lipid carrier to nascent proteins in the endoplasmic reticulum lumen. Biochemical analysis with three biomarkers revealed that N-glycosylation was decreased in the patient's fibroblasts. Complementation with wild-type-DDOST cDNA in patient fibroblasts restored glycosylation, indicating that the mutations were pathological. Our results highlight the power of combining WES and biochemical studies, including a glyco-complementation system, for identifying and confirming the defective gene in an untyped CDG patient. This approach will be very useful for uncovering other types of CDG as well. PMID- 22305528 TI - Haploinsufficiency of a spliceosomal GTPase encoded by EFTUD2 causes mandibulofacial dysostosis with microcephaly. AB - Mandibulofacial dysostosis with microcephaly (MFDM) is a rare sporadic syndrome comprising craniofacial malformations, microcephaly, developmental delay, and a recognizable dysmorphic appearance. Major sequelae, including choanal atresia, sensorineural hearing loss, and cleft palate, each occur in a significant proportion of affected individuals. We present detailed clinical findings in 12 unrelated individuals with MFDM; these 12 individuals compose the largest reported cohort to date. To define the etiology of MFDM, we employed whole-exome sequencing of four unrelated affected individuals and identified heterozygous mutations or deletions of EFTUD2 in all four. Validation studies of eight additional individuals with MFDM demonstrated causative EFTUD2 mutations in all affected individuals tested. A range of EFTUD2-mutation types, including null alleles and frameshifts, is seen in MFDM, consistent with haploinsufficiency; segregation is de novo in all cases assessed to date. U5-116kD, the protein encoded by EFTUD2, is a highly conserved spliceosomal GTPase with a central regulatory role in catalytic splicing and post-splicing-complex disassembly. MFDM is the first multiple-malformation syndrome attributed to a defect of the major spliceosome. Our findings significantly extend the range of reported spliceosomal phenotypes in humans and pave the way for further investigation in related conditions such as Treacher Collins syndrome. PMID- 22305529 TI - DNA methylation signatures in development and aging of the human prefrontal cortex. AB - The human prefrontal cortex (PFC), a mastermind of the brain, is one of the last brain regions to mature. To investigate the role of epigenetics in the development of PFC, we examined DNA methylation in ~14,500 genes at ~27,000 CpG loci focused on 5' promoter regions in 108 subjects range in age from fetal to elderly. DNA methylation in the PFC shows unique temporal patterns across life. The fastest changes occur during the prenatal period, slow down markedly after birth and continue to slow further with aging. At the genome level, the transition from fetal to postnatal life is typified by a reversal of direction, from demethylation prenatally to increased methylation postnatally. DNA methylation is strongly associated with genotypic variants and correlates with expression of a subset of genes, including genes involved in brain development and in de novo DNA methylation. Our results indicate that promoter DNA methylation in the human PFC is a highly dynamic process modified by genetic variance and regulating gene transcription. Additional discovery is made possible with a stand-alone application, BrainCloudMethyl. PMID- 22305530 TI - Age-related somatic structural changes in the nuclear genome of human blood cells. AB - Structural variations are among the most frequent interindividual genetic differences in the human genome. The frequency and distribution of de novo somatic structural variants in normal cells is, however, poorly explored. Using age-stratified cohorts of 318 monozygotic (MZ) twins and 296 single-born subjects, we describe age-related accumulation of copy-number variation in the nuclear genomes in vivo and frequency changes for both megabase- and kilobase range variants. Megabase-range aberrations were found in 3.4% (9 of 264) of subjects >=60 years old; these subjects included 78 MZ twin pairs and 108 single born individuals. No such findings were observed in 81 MZ pairs or 180 single born subjects who were <=55 years old. Recurrent region- and gene-specific mutations, mostly deletions, were observed. Longitudinal analyses of 43 subjects whose data were collected 7-19 years apart suggest considerable variation in the rate of accumulation of clones carrying structural changes. Furthermore, the longitudinal analysis of individuals with structural aberrations suggests that there is a natural self-removal of aberrant cell clones from peripheral blood. In three healthy subjects, we detected somatic aberrations characteristic of patients with myelodysplastic syndrome. The recurrent rearrangements uncovered here are candidates for common age-related defects in human blood cells. We anticipate that extension of these results will allow determination of the genetic age of different somatic-cell lineages and estimation of possible individual differences between genetic and chronological age. Our work might also help to explain the cause of an age-related reduction in the number of cell clones in the blood; such a reduction is one of the hallmarks of immunosenescence. PMID- 22305531 TI - The phenotype of a germline mutation in PIGA: the gene somatically mutated in paroxysmal nocturnal hemoglobinuria. AB - Phosphatidylinositol glycan class A (PIGA) is involved in the first step of glycosylphosphatidylinositol (GPI) biosynthesis. Many proteins, including CD55 and CD59, are anchored to the cell by GPI. Loss of CD55 and CD59 on erythrocytes causes complement-mediated lysis in paroxysmal nocturnal hemoglobinuria (PNH), a disease that manifests after clonal expansion of hematopoietic cells with somatic PIGA mutations. Although somatic PIGA mutations have been identified in many PNH patients, it has been proposed that germline mutations are lethal. We report a family with an X-linked lethal disorder involving cleft palate, neonatal seizures, contractures, central nervous system (CNS) structural malformations, and other anomalies. An X chromosome exome next-generation sequencing screen identified a single nonsense PIGA mutation, c.1234C>T, which predicts p.Arg412(*). This variant segregated with disease and carrier status in the family, is similar to mutations known to cause PNH as a result of PIGA dysfunction, and was absent in 409 controls. PIGA-null mutations are thought to be embryonic lethal, suggesting that p.Arg412(*) PIGA has residual function. Transfection of a mutant p.Arg412(*) PIGA construct into PIGA-null cells showed partial restoration of GPI-anchored proteins. The genetic data show that the c.1234C>T (p.Arg412(*)) mutation is present in an affected child, is linked to the affected chromosome in this family, is rare in the population, and results in reduced, but not absent, biosynthesis of GPI anchors. We conclude that c.1234C>T in PIGA results in the lethal X-linked phenotype recognized in the reported family. PMID- 22305532 TI - Structural and process indicators of nutritional care: a comparison between Austrian hospitals and nursing homes. AB - OBJECTIVE: The aim of this study was to describe and compare structural and process indicators of nutritional care in Austrian hospitals and nursing homes. METHODS: A multicenter, cross-sectional study was performed using a standardized and tested questionnaire. Data were collected on patient and institutional levels of hospitals and nursing homes. RESULTS: Data from 18 Austrian hospitals (n = 2326 patients) and 18 Austrian nursing homes (n = 1487 residents) were collected. The prevalence of malnutrition was 23.2% in hospitals and 26.2% in nursing homes. All hospitals and 83.3% of the nursing homes employed dietitians. Guidelines for the prevention and treatment of malnutrition were used infrequently. Nutritional screening at admission was performed in 62.6% of the hospitalized patients and 93.4% of the nursing home residents. Nutritional screening tools were used in 28.9% of the nursing home residents and 14.5% of the hospitalized patients. Oral nutritional support was preferred to enteral and parenteral nutrition in the two settings. Dietitians were consulted in 27.5% of the malnourished hospitalized patients and 74.7% of the malnourished nursing home residents. CONCLUSION: The study demonstrated that nursing homes fulfilled more structural indicators and performed nutritional screening at admission more often than hospitals. Nevertheless, the prevalence of malnutrition was high in the two settings and a substantial number of malnourished patients/residents received no nutritional intervention at all. These results show the necessity for improvements in the nutritional care in Austria, for instance, through the routine use of nutritional screening tools followed by tailored nutritional interventions in patients/residents in need. PMID- 22305533 TI - Further developments in the neurobiology of food and addiction: update on the state of the science. AB - Over the past three decades, obesity has become a major public health crisis in the United States. The prevalence of obesity in the United States and in other parts of the world has led to a new word, "globesity," being used to describe the problem. As a result of this increased emphasis on understanding the causes and consequences of obesity, novel theories have stimulated new research aimed to prevent, intervene in and ameliorate the effects and decrease the incidence and medical consequences of globesity. One theory that has gained popularity in recent years, is based on the idea that an excessive intake of highly palatable foods shares similarities with the effects on brain and behavior that are seen with some drugs of abuse. Although this theory is not new, empirically-based translational research has only recently provided strong support for this hypothesis. In the present article, we review the present state of the science in this area and describe some newer clinical and preclinical works that shed light on innovative and interesting overlaps between excessivly palatable food intake and drug use. PMID- 22305534 TI - Milk fat globule membrane (INPULSE) enriched formula milk decreases febrile episodes and may improve behavioral regulation in young children. AB - OBJECTIVE: Polar lipids constitute an important part of cellular membranes. The mucosal surface of the gastrointestinal tract is a critical barrier between noxious and immunogenic substances in the lumen and the mucosal immune system. METHODS: We conducted a prospective, double-blinded, randomized, controlled trial in healthy children to evaluate the acceptability, safety, effect on intestinal comfort (constipation), common infectious symptoms (fever, diarrhea, cough), and behavioral regulation of a 4-mo daily intake of 200-mL formula with or without enrichment of the milk fat globule membrane (INPULSE). Data were collected from parental diaries. The primary endpoints for analysis were the number of days with fever, diarrhea, coughing, or constipation. The secondary endpoints were the number of doctor visits, medication intake, number of missed schooldays, acceptability of the test drinks, and safety. The Achenbach System of Empirically Based Assessment, a validated questionnaire to assess behavior, was submitted to parents at the end of the intervention period. RESULTS: Initially 253 children were included, but 71 dropped out (these were subjects with <80% intake or for <90 d). No adverse effects led to the discontinuation. Per-protocol analysis was performed in 97 girls and 85 boys. The group (n = 182) was normally distributed, with a mean age of 4.4 +/- 0.9 y. The amount of product taken each day and the acceptability were similar in the intervention and control groups. The number of days with fever (>38.5 degrees C) and the number of short (<3 d) febrile periods were significantly (P < 0.03) decreased in the intervention group (1.7 +/- 2.5 vs 2.6 +/- 3.1 d) This significant difference in febrile episodes appeared after 6 wk of consecutive intake. Other outcome parameters (diarrhea, constipation, cough, doctor visit, and days of school absence) were similar in the two groups. An analysis of the 169 Achenbach System of Empirically Based Assessment questionnaires (two-tailed t test) showed significant differences in the internal (P < 0.003), external (P < 0.004), and total (P < 0.002) problem scores in favor of the intervention group. Between-subjects effects were highly correlated (internal, P < 0.003; external, P < 0.005; total, P < 0.002, one-way analysis of variance). CONCLUSION: Regular consumption of formula enriched with a concentrated milk fat membrane (INPULSE) product by preschool children was safe, well tolerated, and, based on per-protocol analysis, is associated with a significant decrease in the number of short febrile episodes and leads to improved behavioral regulation. PMID- 22305535 TI - Metabolic syndrome after liver transplantation: is there a role for infections? PMID- 22305536 TI - Changes in ghrelin concentrations one year after resective and non-resective gastric bypass: associations with weight loss and energy and macronutrient intakes. AB - OBJECTIVE: Ghrelin is a potent stimulator of appetite and synthesized in the stomach. Its role in weight loss after gastric bypass (GBP) is still controversial. The aim of this study was to evaluate the relation between weight loss and food intake and between weight loss and changes in serum ghrelin concentrations 1 y after GBP with resection of the bypassed stomach (R-GBP) and without resection (NR-GBP). METHODS: Of 50 women (37.6 +/- 10.2 y old, body mass index 43.8 +/- 4.8 kg/m2) with GBP, 26 had R-GBP and 24 had NR-GBP. Body weight, body composition (dual energy x-ray absorptiometry), food intake, and serum ghrelin at baseline and 12 mo after GBP were measured. RESULTS: The percentage of excess weight loss was 68.9 +/- 12.8% at 12 mo after GBP. At 12 mo, the decrease of serum ghrelin was greater in the R-GBP group (-25.3 +/- 22.5%) compared with the NR-GBP group (+11.2 +/- 50.9%, P < 0.005). After adjustment by the baseline excess of body weight, there was a greater percentage of excess weight loss in the R-GBP group only at 6 mo (61.8% versus 54.9%, P = 0.011). After controlling for the baseline intake, a significant lower carbohydrate intake was observed in the R-GBP group 6 mo after surgery (P < 0.05). CONCLUSION: A greater decrease in ghrelin levels was observed only in patients who underwent R-GBP at 12 mo after surgery. This difference was not associated with differences in dietary intakes or weight loss at the same time point. Therefore, the small gastric pouch is probably more important than decreased ghrelin levels in producing long-term weight loss after R-GBP. PMID- 22305537 TI - Highly efficient synthesis of sucrose monolaurate by alkaline protease Protex 6L. AB - An alkaline protease from Bacillus licheniformis, Protex 6L, was used for synthesis of sucrose monolaurate from sucrose and vinyl laurate in a tert-amyl alcohol/DMSO/water solvent mixture. Introducing sucrose as powder after mixing vinyl laurate with solvent mixture resulted in a higher reaction rate than when sucrose was added as a solution in DMSO. Response surface methodology (RSM) was applied to optimize the major reaction variables, water content, temperature and pH of the lyophilized enzyme. The optimal conditions derived from RSM (3.4% water content, 43 degrees C and pH of 10.1) provided a high initial reaction rate of 8.66 +/- 0.3 mg/ml/h which agreed with the predicted value of 8.70 mg/ml/h. With 1.5 mg-enzyme/ml, 98.0% of the added sucrose was region-selectively converted to 1'-O-lauroylsucrose after 9h. Under the optimized conditions, Protex 6L exhibited a higher productivity for sucrose ester synthesis than Novozym 435 and three other commonly used enzymes. PMID- 22305538 TI - Effects of draw solutions and membrane conditions on electricity generation and water flux in osmotic microbial fuel cells. AB - This study provided an early effort to investigate the draw solutions as catholytes, FO membrane conditions, and backwash for membrane cleaning in an osmotic microbial fuel cell (OsMFC). The results demonstrated that sodium chloride was a suitable candidate as a catholyte solute with good performance in both electricity generation and water flux, although its pH required buffering via acid addition. Adding a small amount of hydrochloric acid decreased the catholyte pH from 9.0 to 2.5 and increased the current generation by 50%, but did not affect water flux. It was also found that the fouled FO membrane improved electricity generation but lost the function of water flux. The damaged FO membrane resulted in a water flux of 0.39 LMH, much lower than 2-3 LMH with a new FO membrane. Backwash with adding NaCl (0.2-0.5M) into the anolyte was examined but did not obviously alleviate membrane fouling. PMID- 22305539 TI - Synergism between microwave irradiation and enzyme catalysis in transesterification of ethyl-3-phenylpropanoate with n-butanol. AB - Lipase catalyzed transesterification was investigated to study the synergistic effect of microwave irradiation and enzyme catalysis. Transesterification of ethyl-3-phenylpropanoate with n-butanol was chosen as the model reaction using immobilized enzymes such as Novozyme 435, Lipozyme RMIM and Lipozyme TL IM with microwave irradiation. Novozyme 435 was the best catalyst. The effect of various parameters affecting the conversion and initial rates of transesterification were studied to establish kinetics and mechanism. There is synergism between enzyme catalysis and microwave irradiation. The analysis of initial rate data and progress curve data showed that the reaction obeys the Ping-Pong bi-bi mechanism with inhibition by n-butanol. The theoretical predictions and experimental data match very well. These studies were also extended to other alcohols such as 2 phenyl-1-propanol, n-octanol, benzyl alcohol, iso-amyl alcohol, 2-hexanol and 2 pentanol under otherwise similar conditions. PMID- 22305540 TI - Improved production of heterologous lipase in Trichoderma reesei by RNAi mediated gene silencing of an endogenic highly expressed gene. AB - A lipase gene (Lip) of the Aspergillus niger was de novo synthesized and expressed in the Trichoderma reesei under the promoter of the cellobiohydrolase I gene (cbh1). RNAi-mediated gene silencing was successfully used to further improve the recombinant lipase production via down-regulation of CBHI which comprised more than 60% of the total extracellular proteins in T. reesei. The gene and protein expression of CBHI and recombinant lipase were analyzed by real time PCR, SDS-PAGE and activity assay. The results demonstrated that RNAi mediated gene silencing could effectively suppress cbh1 gene expression and the reduction of CBHI could result in obvious improvement of heterologous lipase production. The reconstructed strains with decreased CBHI production exhibited 1.8- to 3.2-fold increase in lipase activity than that of parental strain. The study herein provided a feasible and advantageous method of increasing heterologous target gene expression in T. reesei through preventing the high expression of a specific endogenenous gene by RNA interference. PMID- 22305541 TI - Rapid co-pyrolysis of rice straw and a bituminous coal in a high-frequency furnace and gasification of the residual char. AB - Rapid pyrolysis of rice straw (RS) and Shenfu bituminous coal (SB) separately, and rapid co-pyrolysis of RS/SB blends (mass ratio 1:4, 1:4, and 4:1), were carried out in a high-frequency furnace which can ensure both high heating rate and satisfying contact of fuel particles. Synergies between RS and SB during rapid co-pyrolysis were investigated. Intrinsic and morphological structures of residual char from co-pyrolysis, and their effects on gasification characteristics were also studied. Synergies occurred during rapid co-pyrolysis of RS and SB (RS/SB=1:4) resulting in decreasing char yields and increasing volatile yields. Synergies also happened during gasification of the char derived from co-pyrolysis of RS and SB with mass ratio of 1:4. The increased mass ratio of RS to SB did not only weaken synergies during co-pyrolysis, but significantly reduced the gasification rates of the co-pyrolysis char compared to the calculated values. Results can help to optimize co-conversion process of biomass/coal. PMID- 22305542 TI - Molecular drug design, synthesis and crystal structure determination of CuII-SnIV heterobimetallic core: DNA binding and cleavage studies. AB - A novel heterobimetallic Cu(II)-Sn(IV) complex 1 bearing bioactive 1,10 phenanthroline pharmacophore ligand scaffold was synthesized and characterized by elemental analysis, IR, UV-vis spectroscopy, Mass (ESI and FAB) and X-ray crystallography. The in vitro DNA binding studies of complex 1 with CT DNA was carried out by various biophysical and molecular docking techniques which revealed that complex 1 binds to DNA through intercalation in the minor groove having AT-rich sequences. Complex 1 exhibits high chemical nuclease activity cleaving supercoiled pBR322 DNA via hydrolytic pathway which was further evidenced by T4 DNA ligase assay. The complex 1 shows high inhibitory activity against Topo I at a very low concentration (15 MUM), suggesting that complex 1 is an efficient catalytic inhibitor of human Topo I and further validated by molecular docking studies. PMID- 22305543 TI - Synthesis and evaluation of anticancer activity of some novel 6-aryl-2-(p sulfamylphenyl)-pyridazin-3(2H)-ones. AB - A series of novel pyridazinone derivatives bearing benzenesulfonamide moiety (2a h) has been synthesized by the condensation of appropriate aroylacrylic acid and 4-hydrazinobenzenesulfonamide hydrochloride in ethanol. Five derivatives (2a, 2b, 2d, 2g and 2h) were evaluated for their anticancer activity toward human cancer cell lines by the National Cancer Institute. The 2h showed remarkable activity against SR (leukemia) and NCI-H522 (non-small cell lung) with a GI(50) value of less than 0.1 MUM. It also displayed good activity against leukemia (CCRF-CEM, HL 60 (TB), K-562, MOLT-4, RPMI-8226), non-small cell lung cancer (NCI-H460), colon (HCT-116, HCT-15, HT29, KMI2, SW-620), CNS (SF-295), melanoma (MALME-3M, M14, MDA MB-435 SK-MEL-5), ovarian (OVCAR-3, NCI/ADR-RES) and breast (MCF7) cancer cell lines with a GI(50) less than 1.0 MUM. The acute toxicity study of 2h indicated that it is well tolerated intra-peritoneally (400 mg/kg) by athymic nude mice. The 2h may possibly be used as lead compound for developing new anticancer agents. PMID- 22305544 TI - [Methodology of neuroepidemiological studies in tropical countries: a challenge?]. AB - The purpose of this paper is to highlight the difficulties of applying neuroepidemiological methods in low income countries or developing countries, which are mostly tropical countries, taking advantage of the experience of the Institute of Neuroepidemiology and Tropical Neurology, which was created in Limoges in 1982. These difficulties could be related to several aspects: methodological, logistical, political or economical, linked to ethical issues, even difficulties to publish the studies. However, concept and neuroepidemiological methods should stay the same worldwide, even if their translation into practice could sometimes raise some problems in developing countries. Study protocol should be more detailed. Some specific epidemiological methods could be useful. Collection of data should be standardized. True cooperation at every level is needed for these researches to be valid. PMID- 22305545 TI - Cytotoxic T lymphocytes from cattle immunized against Theileria parva exhibit pronounced cross-reactivity among different strain-specific epitopes of the Tp1 antigen. AB - The protozoan parasite Theileria parva causes a usually fatal disease in cattle, known as East Coast fever. Cattle can be vaccinated by injecting live parasites simultaneously with long acting oxytetracycline (the infection and treatment method, ITM). The immunity induced by ITM is believed to be mediated by cytotoxic T lymphocytes (CTL). Although effective, the ITM vaccine has disadvantages such as the need for a liquid nitrogen cold chain and a complex production process, which may be overcome by the development of a subunit vaccine. However, the high level of antigenic polymorphism among different strains of T. parva may hinder the development of a subunit vaccine aimed at induction of a protective CTL response. In this study, the CTL cross-reactivity among T. parva strains was examined. The Tp1(214-224) epitope has previously been shown to be recognized by cattle of the A18 BoLA type. Three different variants of this epitope have been identified from different T. parva strains. Here, bulk CTL and CTL clones were generated from two animals using both the live sporozoite vaccine composed of three different strains and a Muguga strain for immunization. The cross reactivity of these CTL with the three variant Tp1 epitopes was examined in interferon gamma ELISPOT assays and CTL killing assays. CD8(+) cells from both animals cross-reacted with the three variant CTL epitopes in interferon gamma ELISPOT assays, although the CD8(+) cells from the Muguga-immunized animal showed a more epitope restricted response. Clones from the vaccine immunized animal showed diverse response patterns with clones responding to each variant peptide. Although some variability in the cytotoxic response was observed, overall strong cross-reactivity among the variant Tp1 epitopes was seen in both animals. Such epitope polymorphism does not, in this case, serve as a potential challenge in a putative subunit vaccine as it would be sufficient to only include one of the variant epitopes. PMID- 22305546 TI - Cellular interferon-gamma and interleukin-13 immune reactivity in type 1, type 2 and latent autoimmune diabetes: action LADA 6. AB - OBJECTIVE: Type 1 diabetes and latent autoimmune diabetes in adults (LADA) are thought to result from immune-mediated beta-cell destruction. It remains unclear why LADA is clinically less severe compared to type 1 diabetes. This study aimed to compare the pro-inflammatory (interferon-gamma, IFN-gamma) and anti inflammatory (interleukin-13, IL-13) T-cell responses in humans with LADA and type 1 diabetes. RESEARCH DESIGN AND METHODS: IFN-gamma and IL-13 T-cell responses to a panel of 16 (auto)-antigens were tested using an enzyme linked immune-spot technique and peripheral T-cells from 35 patients with type 1 diabetes, 59 patients with type 2 diabetes, 23 LADA patients, and 42 control subjects. RESULTS: LADA and type 1 diabetes patients did not display any statistically significant differences in the frequency of IFN-gamma or IL-13 responses to auto-antigenic stimuli, positive control or mitogen. Overall very low T cell reactivity to autoantigens was detected in all groups. IL-13 responses but not IFN-gamma responses to recall antigen tetanus toxoid were higher in healthy control subjects compared to patients with type 1 or type 2 diabetes or LADA (P<0.05). Diabetes, independent of type, was associated with weaker response to recall antigen tetanus toxoid. CONCLUSIONS: LADA patients are indistinguishable from type 1 diabetes patients for cellular IFN-gamma and IL-13 responses upon mitogen and recall antigen stimulation. These results extend previous findings showing that systemic cytokine/chemokine and humoral responses in type 1 diabetes and LADA are similar. PMID- 22305547 TI - Effects of a comprehensive blood-sparing approach using body weight-adjusted miniaturized cardiopulmonary bypass circuits on transfusion requirements in pediatric cardiac surgery. AB - OBJECTIVES: Transfusion-free pediatric cardiac surgery remains a challenge, mainly owing to the mismatch between the cardiopulmonary bypass (CPB) priming volume and the infants' blood volume. Within a comprehensive blood-sparing approach, we developed body weight-adjusted miniaturized CPB circuits with priming volumes of 95, 110, and 200 mL for, respectively, infants weighing less than 3 kg, 3 to 5 kg and 5 to 16 kg. We analyzed the effects of this approach on transfusion requirements and risk factors predisposing for blood transfusion. METHODS: A total of 288 children with body weights between 1.7 and 15.9 kg were included and divided into 3 groups: No transfusion, postoperative transfusion only, and intraoperative and postoperative transfusion. Groups were compared by analysis of variance or analysis of variance on ranks. Risk factors predisposing for transfusion were identified by multivariate logistic regression. RESULTS: Of the infants, 24.7% required no transfusion, 23.6% received postoperative transfusion only and 51.7% received intraoperative and postoperative transfusion. Groups differed by age, body weight, and size and by duration of surgery, CPB, and aortic crossclamp (P<.00001). Body weight (P<.00001), CPB duration (P<.00001), and persisting cyanosis (P=.03) were predictors of intraoperative and postoperative transfusion, whereas body weight (P=.00095), reoperations (P=.0051), and cyanotic heart defects (P=.035) were associated with postoperative transfusion only. CONCLUSIONS: Our blood-sparing approach allows for transfusion free surgery in a substantial number of infants. The strongest predictors of transfusion requirement, body weight and complexity of surgery as reflected by CPB duration, are not amenable to further improvements. Better preservation of the coagulatory system might allow for reduction of postoperative transfusion requirements. PMID- 22305548 TI - Endoventricular spiral plication for ischemic dilated cardiomyopathy. PMID- 22305549 TI - Totally endoscopic robotic ventricular septal defect repair in the adult. AB - OBJECTIVE: We have previously reported total endoscopic ventricular septal defect repair in the adult using the da Vinci S Surgical System. The optimal results encouraged us to extend the use of this technology to more complicated patients with ventricular septal defect. METHODS: From January 2009 to July 2010, 20 patients underwent total endoscopic robotic ventricular septal defect repair. The average patient age was 29.0 +/- 9.5 years (range, 16-45). Of the 20 patients, 9 were female and 11 were male. The echocardiogram demonstrated that the average diameter of the ventricular septal defect was 6.1 +/- 2.8 mm (range, 2-15), and 4 patients had concomitant patent foramen ovale. Ventricular septal defect closure was directly secured with interrupted mattress sutures in 14 patients and patched in 6 patients. All the procedures were completed using the da Vinci robot by way of 3 port incisions and a 2.0- to 2.5-cm working port in the right side of the chest. RESULTS: All patients were operated on successfully. The mean cardiopulmonary bypass and mean crossclamp time was 94.3 +/- 26.3 minutes (range, 70-140) and 39.1 +/- 12.9 minutes (range, 22-75), respectively. The mean operation time was 225.0 +/- 34.8 minutes (range, 180-300). The postoperative transesophageal echocardiogram demonstrated an intact ventricular septum. No residual left-to-right shunting and no permanently complete atrioventricular dissociation was found postoperatively. The mean hospital stay was 5 days. No residual shunt was found during a mean follow-up of 7 months (range, 1-22). The patients returned to normal function within 1 week without any complications. CONCLUSIONS: Total endoscopic robotic ventricular septal defect repair in adult patients is feasible, safe, and efficacious. PMID- 22305550 TI - Implantation of fetal rat lung fragments into bleomycin-induced pulmonary fibrosis. AB - OBJECTIVE: Pulmonary fibrosis is a life-threatening disease that results in progressive respiratory failure. We have suggested the possibility of fetal lung tissue as an option for further investigation into lung regeneration. The objective was to prove whether fetal lung fragments can survive and differentiate in fibrotic lung. METHODS: Lewis rats were administered bleomycin and used as recipients after 3 or 4 weeks. Day 17 fetal lung tissue from green fluorescent protein Lewis rats was used as donor material. Donor lungs were removed, cut into small pieces, and implanted into the recipients' left lung. The recipients received cyclosporin to prevent immune response to green fluorescent protein and were killed after 1, 2, 4, 8, and 12 weeks and histologically evaluated. Furthermore, the expression of thyroid transcription factor-1 and Clara cell secretory protein in the implanted fetal lung tissue was immunohistologically evaluated. RESULTS: Fibrotic changes were recognized for a long period of time in the recipient lungs. The implanted fetal lung fragments could be clearly distinguished from recipient lungs because of the luminescence of grafts. Fetal lung fragments could survive in the recipient lungs with fibrotic changes. The air spaces of implanted fetal lungs were narrow at 1 and 2 weeks but expanded with the passage of time. The connection between the recipient lung and the implanted fetal lung was recognized, particularly in the peripheral grafts. The expression patterns of thyroid transcription factor-1 and Clara cell secretory protein in implanted lungs resembled those in the process of normal lung morphogenesis. CONCLUSIONS: Fetal rat lung fragments could survive and differentiate in bleomycin-induced completely fibrotic lung. PMID- 22305551 TI - Minimally invasive Ivor Lewis esophagectomy. PMID- 22305552 TI - Diagnosis of infection in patients undergoing extracorporeal membrane oxygenation: a case-control study. AB - OBJECTIVE: Diagnosis of infection in patients receiving extracorporeal membrane oxygenation is challenging in clinical practice but represents a crucial aspect of the upgrading of therapeutic options. The aim of this study was to analyze the role of C-reactive protein and procalcitonin in the diagnosis of infection in patients requiring extracorporeal membrane oxygenation and to assess the difference between venovenous and venoarterial extracorporeal membrane oxygenation settings. METHODS: A case-control study was performed on 27 patients. Serum values of procalcitonin and C-reactive protein were analyzed according to the presence of infection. RESULTS: Forty-eight percent of patients had infection. Gram-negative bacteria were the predominant pathogens, and Candida albicans was the most frequent isolated microorganism. Procalcitonin had an area under the curve of 0.681 (P = .0062) for the diagnosis of infection in the venoarterial extracorporeal membrane oxygenation group but failed to discriminate infection in the venovenous extracorporeal membrane oxygenation group (P = .14). The area under the curve of C-reactive protein was 0.707 (P < .001) in all patients receiving extracorporeal membrane oxygenation. In patients receiving venoarterial extracorporeal membrane oxygenation, procalcitonin had good accuracy with 1.89 ng/mL as the cutoff (sensitivity = 87.8%, specificity = 50%) and C reactive protein with 97.70 mg/L as the cutoff (sensitivity = 85.3%, specificity = 41.6%). The procalcitonin and C-reactive protein combined assay had a sensitivity of 87.2% and specificity of 25.9%. Four variables were identified as statistically significant predictors of infection: procalcitonin and C-reactive protein combined assay (odds ratio, 1.184; P < .001), age (odds ratio, 0.980; P < .001), presence of infection before extracorporeal membrane oxygenation implantation (odds ratio, 1.782; P < .001), and duration of extracorporeal membrane oxygenation support (odds ratio, 1.056; P < .001). CONCLUSIONS: Traditional and emerging inflammatory biomarkers, especially if compounded in the procalcitonin and C-reactive protein combined assay, can aid in the diagnosis of infection in patients undergoing venoarterial extracorporeal membrane oxygenation. PMID- 22305553 TI - Chronic performance of a novel radiofrequency ablation device on the beating heart: Limitations of conduction delay to assess transmurality. AB - OBJECTIVE: The creation of consistently transmural lesions with epicardial ablation on the beating heart has represented a significant challenge for current technology. This study examined the chronic performance of the AtriCure Coolrail device (AtriCure Inc, West Chester, Ohio), an internally cooled, bipolar radiofrequency ablation device designed for off-pump epicardial ablation. The study also examined the reliability of using acute intraoperative conduction delay to evaluate lesion integrity. METHODS: Seven swine underwent median sternotomy. The right atrial appendage and inferior vena cava were isolated with a bipolar radiofrequency clamp. Linear ablation lines were created between these structures with the AtriCure Coolrail. Paced activation maps were recorded with epicardial patch electrodes acutely before and after ablation and after keeping the animals alive for 4 weeks. The conduction time across the linear ablation was calculated from these maps. The lesions were histologically evaluated with trichrome staining. RESULTS: Only 76% of cross-sections of Coolrail lesions were transmural, and only 1 of 12 ablation lines was transmural in every cross-section examined. Mapping data were available in 5 of the animals. Significant conduction delay was present after the creation of each line of ablation acutely; however, after 4 weeks, conduction time returned to preablation values, demonstrating lack of transmurality. CONCLUSIONS: The AtriCure Coolrail failed to reliably create transmural lesions. Although the Coolrail was able to create acute conduction delay, its failure to transmurally ablate the atrial myocardium left gaps along the length of the lesion, which resulted in neither chronic conduction block nor delay across any line of ablation. PMID- 22305554 TI - Angiosarcoma of the breast: a difficult surgical challenge. AB - BACKGROUND AND OBJECTIVES: Breast angiosarcoma presents following radiotherapy after breast conserving surgery, in the setting of chronic lymphoedema after axillary dissection or as a primary tumour. The Peter MacCallum Cancer Centre has significant experience due to large breast and sarcoma units and as a primary radiotherapy centre. Our aims were to evaluate the management and locoregional and distant outcomes after breast angiosarcoma. METHODS: Retrospective study of all patients from the prospective breast and sarcoma databases with a diagnosis of primary or secondary breast angiosarcoma at Peter MacCallum Cancer Centre was performed between January 2000 and December 2010. Mode of presentation, management, loco-regional recurrence and survival rates were reviewed. RESULTS: Eight women developed angiosarcoma in the setting of breast conservation with a median latency of 7 years post radiotherapy. Six patients had primary breast angiosarcoma. All breast angiosarcomas were managed with total mastectomy with 5 patients requiring autologous tissue transfer. Four patients had adjuvant radiotherapy and three patients had adjuvant paclitaxel. The median follow-up was 2.5 years (6 month-10 years) with 7 episodes of local recurrence in four patients and 7 patients with distal metastases including two deaths from distant disease. CONCLUSIONS: Primary angiosarcoma occurs de novo, presenting as a breast mass. Secondary angiosarcoma presents predominantly as a skin lesion, in the setting post-operative radiotherapy for breast conserving therapy. Angiosarcoma remains a rare and difficult management problem with poor loco-regional and distal control. Secondary AS is an iatrogenic condition that warrants close follow-up and judicial use of radiotherapy in breast conserving therapy. PMID- 22305555 TI - Study of the cultivable microflora of the large intestine of the rat under varied environmental hyperbaric pressures. AB - BACKGROUND/PURPOSE(S): We conducted an in vivo experiment to investigate the effect of hyperbarometric air pressure on the quantity and composition of the cultivable microflora of the large intestine. METHODS: Using selective culture based methods, we enumerated from the large intestine total aerobes and total anaerobes, and indicator bacteria such as Escherichia coli, other Enterobacteriaceae, Bifidobacterium spp., Lactobacillus spp. and Clostridium perfringens, and studied their quantitative variation. RESULTS: Total aerobes and facultative anaerobes (E. coli and other Enterobacteriaceae) were increased with an increase in air pressure, whereas the increase caused a drastic reduction in the numbers of total anaerobes and Clostridium perfringens. Bifidobacterium spp. and Lactobacillus spp. were affected slightly by the altered air pressures. Variation in the numbers of these groups of bacteria was correlated to dose and duration of hyperbaric treatment. CONCLUSION: We conclude from our results that air pressure is an important exogenous factor that strongly modulates bacterial colonization of the large intestine and the composition of the intestinal microflora, and that the occurrence of gastrointestinal disorders during hyperbarism is a result of alteration in the indigenous microflora. PMID- 22305556 TI - Infection-induced hematopoiesis: a zebrafish perspective. AB - In response to infection, the bone marrow adjusts production of leukocyte cell types to fight off disease. In this issue of Cell Stem Cell, Hall et al. (2012) use the zebrafish model to show that nitric oxide (NO) production drives expansion of hematopoietic progenitors to produce more granulocytes. PMID- 22305557 TI - Stem-cell-like qualities of immune memory; CD4+ T cells join the party. AB - Similar to hematopoietic stem cells, memory lymphocytes self-renew, while their clonally expanded effector progeny differentiate to fight infection and tumors. Recently, Muranski et al. (2011) report in Immunity that a subset of Th17 effector cells function as memory cells and retain stem cell properties. PMID- 22305558 TI - Common signaling networks characterize leukemia-initiating cells in acute myeloid leukemia. AB - Identification and characterization of leukemia-initiating cells (LICs) is important to understand leukemogenesis and develop novel therapies for leukemia. In this issue of Cell Stem Cell, Gibbs et al. (2012) demonstrate that common active signaling pathways in LICs may be targeted to treat acute myeloid leukemia. PMID- 22305559 TI - Periostin: a bridge between cancer stem cells and their metastatic niche. AB - Only a minority of cancer cells have the potential to initiate metastatic growth, but the factors that limit metastatic colonization remain mostly unknown. Malanchi et al. (2012) recently demonstrated that stromal periostin is crucial for metastatic colonization by regulating the interactions between breast cancer stem cells and their metastatic niche. PMID- 22305560 TI - Engineering stem cell expansion. AB - In this issue of Cell Stem Cell, Csaszar et al. (2012) develop a culture method that overcomes current limitations in ex vivo hematopoietic stem/progenitor cell expansion by continuously diluting inhibitory signaling factors and maintaining stem cell density. This approach enhances the generation of precursors with potential therapeutic utility. PMID- 22305561 TI - The potential of stem cells as an in vitro source of red blood cells for transfusion. AB - Recent advances have increased excitement about the potential for therapeutic production of red blood cells (RBCs) in vitro. However, generation of RBCs in the large numbers required for transfusion remains a significant challenge. In this article, we summarize recent progress in producing RBCs from various cell sources, and discuss the hurdles that remain for translation into the clinical arena. PMID- 22305562 TI - Hematopoiesis: a human perspective. AB - Despite its complexity, blood is probably the best understood developmental system, largely due to seminal experimentation in the mouse. Clinically, hematopoietic stem cell (HSC) transplantation represents the most widely deployed regenerative therapy, but human HSCs have only been characterized relatively recently. The discovery that immune-deficient mice could be engrafted with human cells provided a powerful approach for studying HSCs. We highlight 2 decades of studies focusing on isolation and molecular regulation of human HSCs, therapeutic applications, and early lineage commitment steps, and compare mouse and humanized models to identify both conserved and species-specific mechanisms that will aid future preclinical research. PMID- 22305564 TI - Advancing stem cell biology toward stem cell therapeutics. AB - Here, the International Society for Stem Cell Research (ISSCR) Clinical Translation Committee introduces a series of disease-specific articles, outlining the challenges surrounding the clinical translation of stem cell therapeutics. PMID- 22305563 TI - Hematopoietic-stem-cell-based gene therapy for HIV disease. AB - Although combination antiretroviral therapy can dramatically reduce the circulating viral load in those infected with HIV, replication-competent virus persists. To eliminate the need for indefinite treatment, there is growing interest in creating a functional HIV-resistant immune system through the use of gene-modified hematopoietic stem cells (HSCs). Proof of concept for this approach has been provided in the instance of an HIV-infected adult transplanted with allogeneic stem cells from a donor lacking the HIV coreceptor, CCR5. Here, we review this and other strategies for HSC-based gene therapy for HIV disease. PMID- 22305565 TI - Clinical translation of stem cells in neurodegenerative disorders. AB - Stem cells and their derivatives show tremendous potential for treating many disorders, including neurodegenerative diseases. We discuss here the challenges and potential for the translation of stem-cell-based approaches into treatments for Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. PMID- 22305566 TI - Polycomb associates genome-wide with a specific RNA polymerase II variant, and regulates metabolic genes in ESCs. AB - Polycomb repressor complexes (PRCs) are important chromatin modifiers fundamentally implicated in pluripotency and cancer. Polycomb silencing in embryonic stem cells (ESCs) can be accompanied by active chromatin and primed RNA polymerase II (RNAPII), but the relationship between PRCs and RNAPII remains unclear genome-wide. We mapped PRC repression markers and four RNAPII states in ESCs using ChIP-seq, and found that PRC targets exhibit a range of RNAPII variants. First, developmental PRC targets are bound by unproductive RNAPII (S5p(+)S7p(-)S2p(-)) genome-wide. Sequential ChIP, Ring1B depletion, and genome wide correlations show that PRCs and RNAPII-S5p physically bind to the same chromatin and functionally synergize. Second, we identify a cohort of genes marked by PRC and elongating RNAPII (S5p(+)S7p(+)S2p(+)); they produce mRNA and protein, and their expression increases upon PRC1 knockdown. We show that this group of PRC targets switches between active and PRC-repressed states within the ESC population, and that many have roles in metabolism. PMID- 22305567 TI - BMP4 Signaling Acts via dual-specificity phosphatase 9 to control ERK activity in mouse embryonic stem cells. AB - Extrinsic BMP and LIF signaling collaboratively maintain mouse embryonic stem cell (ESC) pluripotency, whereas appropriate ERK activity is essential for ESC fate commitment. However, how the extrinsic signals restrain appropriate ERK activity remains elusive. Here, we show that, whereas LIF sustains relatively high ERK activity, BMP4 can steadily attenuate ERK activity by upregulating ERK specific dual-specificity phosphatase 9 (DUSP9). This upregulation requires Smad1/5 and Smad4 and specifically occurs to DUSP9, but not other DUSPs, and only in ESCs. Through DUSP9-mediated inhibition of ERK activity, BMP signaling reinforces the self-renewal status of mouse ESCs together with LIF. Upon LIF withdrawal, ESCs spontaneously undergo neural differentiation, during which process DUSP9 can partially mediate BMP inhibition on neural commitment. Collectively, our findings identify DUSP9 as a critical mediator of BMP signaling to control appropriate ERK activity critical for ESC fate determination. PMID- 22305568 TI - A mammary stem cell population identified and characterized in late embryogenesis reveals similarities to human breast cancer. AB - Gene expression signatures relating mammary stem cell populations to breast cancers have focused on adult tissue. Here, we identify, isolate, and characterize the fetal mammary stem cell (fMaSC) state since the invasive and proliferative processes of mammogenesis resemble phases of cancer progression. fMaSC frequency peaks late in embryogenesis, enabling more extensive stem cell purification than achieved with adult tissue. fMaSCs are self-renewing, multipotent, and coexpress multiple mammary lineage markers. Gene expression, transplantation, and in vitro analyses reveal putative autocrine and paracrine regulatory mechanisms, including ErbB and FGF signaling pathways impinging on fMaSC growth. Expression profiles from fMaSCs and associated stroma exhibit significant similarities to basal-like and Her2+ intrinsic breast cancer subtypes. Our results reveal links between development and cancer and provide resources to identify new candidates for diagnosis, prognosis, and therapy. PMID- 22305569 TI - Infection-responsive expansion of the hematopoietic stem and progenitor cell compartment in zebrafish is dependent upon inducible nitric oxide. AB - Hematopoietic stem cells (HSCs) are rare multipotent cells that contribute to all blood lineages. During inflammatory stress, hematopoietic stem and progenitor cells (HSPCs) can be stimulated to proliferate and differentiate into the required immune cell lineages. Manipulating signaling pathways that alter HSPC capacity holds great promise in the treatment of hematological malignancies. To date, signaling pathways that influence HSPC capacity, in response to hematopoietic stress, remain largely unknown. Using a zebrafish model of demand driven granulopoiesis to explore the HSPC response to infection, we present data supporting a model where the zebrafish ortholog of the cytokine-inducible form of nitric oxide synthase (iNOS/NOS2) Nos2a acts downstream of the transcription factor C/ebpbeta to control expansion of HSPCs following infection. These results provide new insights into the reactive capacity of HSPCs and how the blood system is "fine-tuned" in response to inflammatory stress. PMID- 22305570 TI - Decoupling of tumor-initiating activity from stable immunophenotype in HoxA9 Meis1-driven AML. AB - Increasing evidence suggests tumors are maintained by cancer stem cells; however, their nature remains controversial. In a HoxA9-Meis1 (H9M) model of acute myeloid leukemia (AML), we found that tumor-initiating activity existed in three, immunophenotypically distinct compartments, corresponding to disparate lineages on the normal hematopoietic hierarchy--stem/progenitor cells (Lin(-)kit(+)) and committed progenitors of the myeloid (Gr1(+)kit(+)) and lymphoid lineages (Lym(+)kit(+)). These distinct tumor-initiating cells (TICs) clonally recapitulated the immunophenotypic spectrum of the original tumor in vivo (including cells with a less-differentiated immunophenotype) and shared signaling networks, such that in vivo pharmacologic targeting of conserved TIC survival pathways (DNA methyltransferase and MEK phosphorylation) significantly increased survival. Collectively, H9M AML is organized as an atypical hierarchy that defies the strict lineage marker boundaries and unidirectional differentiation of normal hematopoiesis. Moreover, this suggests that in certain malignancies tumor initiation activity (or "cancer stemness") can represent a cellular state that exists independently of distinct immunophenotypic definition. PMID- 22305571 TI - Rapid expansion of human hematopoietic stem cells by automated control of inhibitory feedback signaling. AB - Clinical hematopoietic transplantation outcomes are strongly correlated with the numbers of cells infused. Anticipated novel therapeutic implementations of hematopoietic stem cells (HSCs) and their derivatives further increase interest in strategies to expand HSCs ex vivo. A fundamental limitation in all HSC-driven culture systems is the rapid generation of differentiating cells and their secreted inhibitory feedback signals. Herein we describe an integrated computational and experimental strategy that enables a tunable reduction in the global levels and impact of paracrine signaling factors in an automated closed system process by employing a controlled fed-batch media dilution approach. Application of this system to human cord blood cells yielded a rapid (12-day) 11 fold increase of HSCs with self-renewing, multilineage repopulating ability. These results highlight the marked improvements that control of feedback signaling can offer primary stem cell culture and demonstrate a clinically relevant rapid and relatively low culture volume strategy for ex vivo HSC expansion. PMID- 22305572 TI - Cyclodextrins adsorbed onto activated carbons: preparation, characterization, and effect on the dispersibility of the particles in water. AB - We have investigated the adsorption equilibrium of selected cyclodextrins onto activated carbons. A number of parameters were examined including the type of carbon material, the size of macrocyclic cavity, and the chemical nature of the oligosaccharide (e.g., neutral, anionic, or cationic cyclodextrin). Adsorption isotherm studies revealed that the maximum amount of cyclodextrin immobilized on the carbon surface is obtained for the native beta-CD, while the adsorption capacity of the ionic cyclodextrins derivatives strongly depends on the net surface charge of the activated carbon. The affinity of cyclodextrins for activated carbons was further utilized to prepare modified activated carbons containing controlled amounts of cyclodextrins through an adsorption process. The resulting materials were characterized by N(2) adsorption-desorption volumetric measurements, FTIR and Raman spectroscopy, while the quantitative determination of the oligosaccharide content on activated carbons was performed by gravimetric measurements. On the basis of the Turbiscan results, it was found that the chemical structure of cyclodextrins, which are incorporated in the carbon framework, had significant influence on the dispersibility and stabilization of the solid particles in water. Agglomeration and precipitation of the carbon particles were markedly suppressed with substituted cyclodextrins whose hydroxyl groups were partially substituted by methyl or alkylammonium groups. PMID- 22305573 TI - Interfacial concentrations of chloride and bromide in zwitterionic micelles with opposite dipoles: experimental determination by chemical trapping and a theoretical description. AB - Interfacial concentrations of chloride and bromide ions, with Li(+), Na(+), K(+), Rb(+), Cs(+), trimethylammonium (TMA(+)), Ca(2+), and Mg(2+) as counterions, were determined by chemical trapping in micelles formed by two zwitterionic surfactants, namely N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (HPS) and hexadecylphosphorylcholine (HDPC) micelles. Appropriate standard curves for the chemical trapping method were obtained by measuring the product yields of chloride and bromide salts with 2,4,6-trimethyl-benzenediazonium (BF(4)) in the presence of low molecular analogs (N,N,N-trimethyl-propane sulfonate and methyl phosphorylcholine) of the employed surfactants. The experimentally determined values for the local Br(-) (Cl(-)) concentrations were modeled by fully integrated non-linear Poisson Boltzmann equations. The best fits to all experimental data were obtained by considering that ions at the interface are not fixed at an adsorption site but are free to move in the interfacial plane. In addition, the calculation of ion distribution allowed the estimation of the degree of ion coverage by using standard chemical potential differences accounting for ion specificity. PMID- 22305574 TI - Uniform metal nanoparticles produced at high yield in dense microemulsions. AB - This article demonstrates that bicontinuous microemulsions are optimal templates for high yield production of metal nanoparticles. We have verified this for a variety of microemulsion systems having AOT (sodium bis (2-ethyhexyl) sulphosuccinate) or a fluorocarbon (perfluoro (4-methyl-3,6 dioxaoctane)sulphonate) as surfactant mixed with water and oils like n-heptane or n-dodecane. Several types of metal nanoparticles, including platinum, gold and iron, were produced in these microemulsions having a size range spanning 1.8-17 nm with a very narrow size distribution of +/-1 nm. Remarkably high mass concentrations up to 3% were reached. Size and concentration of the nanoparticles could be varied with the stoichiometries of the reagents that constituted them. The optimization towards high yield while maintaining low size polydispersity is due to the decoupling of the time scales for the precipitation reaction and for coarsening. In actual fact, coalescence is essentially prevented by the immobilization of nanoparticles within the bicontinuous microemulsion structure. PMID- 22305575 TI - Mass transport characteristics of alkyl amines in a water/n-decane system. AB - Water-in-decane emulsions can be applied as reaction system for the precipitation of nanoparticles. Herein the precipitation reaction is induced once an oil as well as water soluble compound (here: alkyl amines) diffuses from the continuous oil phase into a water based droplet, loaded with the reaction partner. Thus, the mass transfer and adsorption characteristics of the alkyl amine at the interface are key parameters to understand particle formation in emulsion droplets. For this reason, the effective diffusion coefficients and the interfacial tension of different alkyl amines in a water/n-decane system were estimated. Furthermore, emulsifiers necessary for the stability of the emulsion might represent a diffusion barrier. In order to determine its influence, diffusion experiments were also conducted in the presence of emulsifier. The effective diffusion coefficients were measured using an adapted photometric method. To identify relevant adsorption characteristics of the water/n-decane/alkyl amine systems, the interfacial tension was studied with the pendant drop technique. According to the results, we can draw three conclusions: First, the effective diffusion coefficient depends on the molecular structure of the amines. Second, regarding our materials, the surface activity and surface coverage proved to be a governing parameter to describe differences in the transport mechanism. And third, the presence of additional surface active compounds leads to a decrease of the effective diffusion coefficient. PMID- 22305576 TI - Characterisation of alkyl amines at the water/air surface with the drop and bubble profile analysis tensiometry. AB - Pendant drop and buoyant bubble methods have been used to study the surface characteristics of alkyl amines at the water/air surface. The investigated alkyl amines, triethylamine and octylamine, showed unusual changes in the surface tension as a function of time: an initially steep drop and a subsequent steady increase in the surface tension until a value close to the one of the pure water/air system was observed. This phenomenon is explained by the evaporation of the alkyl amines, for which several sets of experiments have been conducted with the pendant drop and buoyant bubble methods. Using an appropriate experimental protocol, the equilibrium adsorption behaviour of the two amines can be quantitatively measured. PMID- 22305577 TI - Shell modulation by tailoring substituents in chitosan for LbL-assembled microcapsules. AB - By AFM we report the successful modulation of shell structure (morphology and shell thickness) of microcapsules through tailoring molecular substituents of chitosan. The shell thickness of hollow (HPCS/SA)(n) (n=5, 7, 9) capsules is more than 3 times that of the (QACS/SA)(n) (n=5, 7, 9) capsules, due to less charges carried by the neutral -NH(2) substituent group and the induced coily conformation in HPCS, while more charges carried by the positively charged N(CH(3))(3)(+) substituent and the induced extended conformation in QACS (HPCS: hydroxyl propyl chitosan; QACS: quaternary ammonium chitosan; SA: sodium alginate). The ultrathin shells of microcapsules assembled in this work by the layer-by-layer (LbL) self-assembly technique rather than the traditional method of mixing CS, SA and CaCl(2) enable the thickness modulation characterization by AFM on the atomic scale. These microcapsules with tunable shell thickness provide important guidance for potential drug delivery and sustained release. PMID- 22305578 TI - The cardiovascular risk profile of atherosclerotic gastrointestinal ischemia is different from other vascular beds. AB - BACKGROUND: The distribution of cardiovascular risk factors in patients with chronic gastrointestinal ischemia due to atherosclerosis of the splanchnic vessels (chronic splanchnic syndrome) is not well studied. The aim of this study was to determine the cardiovascular risk factor pattern in patients with chronic splanchnic syndrome. METHODS: From April 2003 to September 2007, atherosclerotic risk factors in consecutive patients with chronic splanchnic syndrome were compared prospectively with the general atherosclerotic risk profile in Western Europe and worldwide risk profile of coronary heart disease, peripheral artery disease, and cerebral vascular disease. RESULTS: Of 376 analyzed patients, 97 were diagnosed with chronic splanchnic syndrome. Data from 90 patients were available for analysis (7 were excluded because of incomplete data). Mean age was 63 years (range 28-86 years), and 74% were female. Fifty-nine percent of the patients had atherosclerotic disease in other vascular beds. Smoking was reported in 57%, and increased bodyweight in 21%. Hypercholesterolemia was present in 53%, hypertension in 62%, and diabetes in 21%. CONCLUSIONS: The atherosclerotic risk profile in patients with chronic splanchnic syndrome differed from other atherosclerotic diseases with a female preponderance, lower incidence of obesity/increased bodyweight, diabetes, hypertension, and hypercholesterolemia. Reduced caloric intake, related to the postprandial pain, may explain the observed differences. PMID- 22305579 TI - Variation of fasting plasma glucose: a predictor of mortality in patients with type 2 diabetes. AB - BACKGROUND: The aim of this study was to examine whether time-dependent annual fasting plasma glucose (FPG) variation, as represented by coefficient of variation (CV), can predict mortality in subsequent all-cause, expanded, and nonexpanded cardiovascular disease-related mortality independent of mean FPG, renal function, mean hemoglobin A(1)C (HbA(1C)), HbA(1C) variation, and other risk factors in patients with type 2 diabetes. METHODS: A computerized database of all patients with type 2 diabetes aged 30 years and over (n = 5008) enrolled in the Diabetes Care Management Program of China Medical University Hospital before 2007 was used in a time-dependent Cox proportional hazard regression model. RESULTS: The mortality rates were 8.64, 12.71, and 30.82 per 1000 person years in groups of first, second, and third tertiles of baseline FPG-CV, respectively. Among these patients with type 2 diabetes, 336, 1191, 914, 585, and 1979 patients provided 1, 2, 3, 4, and 5 or more years of annual FPG-CV measurements, respectively. After adjusting for mean FPG, mean HbA(1C), HbA(1C) variation, and other risk factors, annual FPG-CV was independently associated with all-cause mortality and mortality due to expanded and nonexpanded cardiovascular disease, and the corresponding hazard ratios for third versus first tertile of annual FPG-CV were 5.53 (95% confidence interval [CI], 3.85 7.94), 3.21 (95% CI, 2.00-5.15), and 9.45 (95% CI, 5.37-16.63), respectively. CONCLUSIONS: Time-dependent variation of FPG was a strong predictor of all-cause, expanded, and nonexpanded cardiovascular disease-related mortality in patients with type 2 diabetes, suggesting that glucose variation may become a measure in clinical practice for the goal in the management of these patients. PMID- 22305580 TI - Ghostwriting: research misconduct, plagiarism, or fool's gold? PMID- 22305581 TI - Suppression of adipogenesis in mouse mesenchymal stem cells by imipramine. AB - Imipramine (IM) has been widely used in clinics for the treatment of some mental diseases. The understanding of its role in other tissues or organs will be beneficial for its better clinical use. Here, it is shown that IM suppresses the adipogenic differentiation of mouse mesenchymal stem cells (MSCs). The accumulation of intracellular, Oil red O-stained lipid droplets was inhibited by IM in a dose-dependent manner. RT-PCR and western blot analysis revealed that after IM loading, the expression of peroxisome proliferator-activated receptor gamma2 (PPARgamma2) decreased, demonstrating that the suppression of IM on MSC adipogenesis is at least partially mediated by the PPARgamma2 pathway. These findings suggest that, in appropriate doses, the conventional antidepressive (IM) may exert inhibitory effect on adipocyte formation. PMID- 22305582 TI - Syntheses of structurally-simplified and fluorescently-labeled neovibsanin derivatives and analysis of their neurite outgrowth activity in PC12 cells. AB - The syntheses of several neovibsanin derivatives were carried out in order to elucidate the simple structure required for displaying neurite outgrowth activity. In addition, a fluorescent probe molecule was synthesized and the analysis of its behavior in the PC12 cell line showed that the neovibsanins accumulate on the outer edge of the cell at the site of formation of prominences. PMID- 22305583 TI - Discovery of 3,4-dihydropyrimidin-2(1H)-ones with inhibitory activity against HIV 1 replication. AB - 3,4-Dihydropyrimidin-2(1H)-ones (DHPMs) were selected and derivatized through a HIV-1 replication assay based on GFP reporter cells. Compounds 14, 25, 31, and 36 exhibited significant inhibition of HIV-1 replication with a good safety profile. Chiral separation of each enantiomer by fractional crystallization showed that only the S enantiomer retained anti-HIV activity. Compound (S)-40, a novel and potent DHPM analog, could serve as an advanced lead for further development and the determination of the mechanism of action. PMID- 22305584 TI - Discovery of azabenzimidazole derivatives as potent, selective inhibitors of TBK1/IKKepsilon kinases. AB - The design, synthesis and biological evaluation of a series of azabenzimidazole derivatives as TBK1/IKKepsilon kinase inhibitors are described. Starting from a lead compound 1a, iterative design and SAR exploitation of the scaffold led to analogues with nM enzyme potencies against TBK1/IKKepsilon. These compounds also exhibited excellent cellular activity against TBK1. Further structure-based design to improve selectivity over CDK2 and Aurora B resulted in compounds such as 5b-e. These probe compounds will facilitate study of the complex cancer biology of TBK1 and IKKepsilon. PMID- 22305585 TI - Non-linear classification of heart rate parameters as a biomarker for epileptogenesis. AB - PURPOSE: To characterize a biomarker for epileptogenesis based on cardiac interbeat interval characteristics. METHODS: Electrocardiograph (ECG) and electroencephalogram (EEG) signals were recorded from freely moving rats (n = 23) before status epilepticus (SE) induced by i.p. pilocarpine (PILO) injection as baseline, and on days 1, 3 and 7 after SE. We assessed several features from cardiac interbeat intervals, including linear, non-linear and frequency parameters of interbeat intervals, and power spectra of interpolated intervals during epileptogenesis. After thresholding, the altered values were applied to a non-linear classifier. The non-linear classifier divided animals into two groups; with and without epilepsy, based on all collected data. RESULTS: We found that none of the single altered parameters in cardiac activity emerged as a sole biomarker for epileptogenesis. However, the non-linear classifier distinguished animals that later developed from those and did not develop epilepsy. The non linear classification was performed on preliminary findings from 23 animals; six did not develop epilepsy and the rest did. The average positive predictive value (precision rate) was 78%. This was calculated based on the average sensitivity and specificity, which were 80.6% and 35.2% respectively, for the 100 classification passes. We also showed that these numbers would have increased as the number of subjects increased. CONCLUSION: Changes to the brain caused by status epilepticus that lead to epileptogenesis have systemic effects, and alter cardiac activity. A non-linear classifier performed on several extracted features of cardiac interbeat intervals may be useful as a biomarker to identify animals with low and high probability of developing epilepsy after status epilepticus. PMID- 22305586 TI - Jigger flea infestation (tungiasis) in rural western Tanzania: high prevalence and severe morbidity. AB - Epidemiologic and clinical data on the parasitic skin disease tungiasis are limited from sub-Saharan Africa, and virtually nonexistent from the East African region. We performed a community-based cross-sectional study in two villages in Kasulu district, western Tanzania. Study participants were examined for the presence of tungiasis and disease-associated morbidity. In total, 586 individuals >5 years of age were enrolled, and 249 (42.5%; 95% CI: 38.5-46.5) diagnosed with tungiasis. The >=45 year-olds showed highest prevalence of tungiasis (71.1%) and most severe parasite load (median number of embedded fleas: 17.5; interquartile range: 15-22.5). Prevalence was slightly, but not significantly, higher in males than in females (45.3 vs 39.7%; p=0.17). Itching (68.3%), pain (38.6%) and ulcers (30.1%) were common; 22.1% of individuals found it difficult to walk due to tungiasis, and in 21.3% loss of toenails was observed. Considering the high prevalence and considerable morbidity in the population, we conclude that tungiasis is a public health threat in the study villages and that the disease needs to be recognized by health authorities. Future studies on risk factors, animal reservoirs and evidence-based control measures are needed. PMID- 22305587 TI - Multidisciplinary trauma team care in Kandahar, Afghanistan: current injury patterns and care practices. AB - Multidisciplinary trauma care systems have been shown to improve patient outcomes. Medical care in support of the global war on terror has provided opportunities to refine these systems. We report on the multidisciplinary trauma care system at the Role III Hospital at Kandahar Airfield, Afghanistan. We reviewed the Joint Trauma System Registry, Kandahar database from 1 October 2009 to 31 December 2010 and extracted data regarding patient demographics, clinical variables and outcomes. We also queried the operating room records from 1 January 2009 to 31 December 2010. In the study period of 1 October 2009 to 31 December 2010, 2599 patients presented to the trauma bay, with the most common source of injury being from Improvised Explosive Device (IED) blasts (915), followed by gunshot wounds (GSW) (327). Importantly, 19 patients with triple amputations as a result of injuries from IEDs were seen. 127 patients were massively transfused. The in-hospital mortality was 4.45%. From 1 January 2010 to 31 December 2010, 4106.24 operating room hours were logged to complete 1914 patient cases. The mean number of procedures per case in 2009 was 1.27, compared to 3.11 in 2010. Multinational, multidisciplinary care is required for the large number of severely injured patients seen at Kandahar Airfield. Multidisciplinary trauma care in Kandahar is effective and can be readily employed in combat hospitals in Afghanistan and serve as a model for civilian centres. PMID- 22305588 TI - The effect of Helicopter Emergency Medical Services on trauma patient mortality in the Netherlands. AB - INTRODUCTION: Object of this study was to evaluate the effect of the Helicopter Emergency Medical Services (HEMS) on trauma patient mortality and the effect of prehospital time on the association between HEMS and mortality. MATERIALS AND METHODS: Trauma patients admitted to a level 1 trauma centre and treated on-scene by the HEMS and Emergency Medical Services (EMS) between 2003 and 2008 were included (n = 186). A control group treated by EMS only (n = 186) was created by matching on ISS, age and severe traumatic brain injury (TBI). Mortality was compared by calculating odds ratios (OR) and numbers needed to treat (NNT), with adjustment for prehospital coded Revised Trauma Score. The effect of prehospital time mortality was tested by a logistic regression. Analyses were made for patients with and without TBI. RESULTS: The OR of early trauma fatality for the HEMS/EMS versus EMS-only groups was 0.8 for patients both with TBI (95% CI 0.4 1.7; NNT: 22) and without TBI (95% CI 0.2-3.3; NNT: 273). The risk of in-hospital mortality was non-significantly higher for patients with TBI in the HEMS/EMS group (OR = 1.3; 95% CI 0.6-2.7; NNT: -15) compared to the EMS-only group and non significantly lower for patients without TBI (OR = 0.9; 95% CI 0.3-2.5; NNT: 129). After adjustment for prehospital time, the risk of early trauma fatality for patients with TBI treated by the HEMS decreased (OR = 0.6; 95% CI 0.3-1.6). The risk of in-hospital mortality for these patients decreased from 1.3 to 0.8 (95% CI 0.4-2.0). The effect of the HEMS on patients without TBI did not change after adjustment for prehospital time. DISCUSSION: HEMS treatment is associated with a non-significantly higher risk of in-hospital mortality for patients with TBI and a non-significantly lower risk for patients without TBI. This increased risk of mortality in TBI patients is attributable to the increased prehospital time. These results indicate that HEMS does not have a positive impact on survival. PMID- 22305590 TI - The inflammatory breast. PMID- 22305589 TI - Case study of the relationship between fungi and bacteria associated with high molecular-weight polycyclic aromatic hydrocarbon degradation. AB - Although bacteria play dominant roles in microbial bioremediation, few of them have been reported that were capable of utilizing high-molecular-weight (HMW) organic pollutants as their sole sources of carbon and energy. However, many soil fungi can metabolize those of pollutants, although they rarely complete mineralization. In this paper, we investigated the dynamic relationship between fungi and bacteria associated with degradation of HMW-polycyclic aromatic hydrocarbons (PAHs). Artificial fungal-bacterial mixed cultures were constructed to simulate the environment of actual polluted sites. Four bacterial strains and seven fungal strains were isolated that related to the removal of phenanthrene, fluoranthene and pyrene in the soil. Furthermore, these strains were used to create mixed culture of bacteria (Bact-mix), mixed culture of fungi (Fung-mix), fungal-bacterial co-cultures (Fung-Bact), respectively. The maximal pyrene removal rate (67%, 28days) was observed in the Fung-Bact, compared with cultures of Fung-mix (39%) and Bact-mix (56%). The same tendency was also indicated in the degradation of phenanthrene and fluoranthene. In addition, a dynamic relationship during the degradation process between fungi and bacteria was monitored through using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR DGGE) method. PMID- 22305591 TI - Breast inflammation: clinical examination, aetiological pointers. AB - Red, hot, and painful breast inflammation can have a large number of causes. The history of the condition and clinical observations usually give a pointer to the aetiological diagnosis, which is based on the classic triad of clinical, radiological and histopathological examinations, and guide the choice of additional investigations for rapid therapeutic management of this breast emergency. In breastfeeding women, the cause is often mastitis or, more rarely, an abscess; in non-breastfeeding women, the problem may be mastitis or a periareolar abscess, inflammatory lesions sometimes with secondary infection, or more rarely a real abscess, regardless of a catalogue of various causes. In all cases, the possibility must be considered of inflammatory breast cancer. PMID- 22305592 TI - Imaging benign inflammatory syndromes. AB - Benign mastitis is a rare disease and its management is difficult. The diagnostic challenge is to distinguish it from carcinomatous mastitis. We make a distinction between acute mastitis secondary to an infection, to inflammation around a benign structure or to superficial thrombophlebitis, and chronic, principally plasma cell and idiopathic granulomatous mastitis. Imaging is often non-specific but we need to know and look for certain ultrasound, mammogram or magnetic resonance imaging (MRI) signs to give a pointer as early as possible towards a benign aetiology. A biopsy should be undertaken systematically where there is the slightest diagnostic doubt, to avoid failing to recognise a carcinomatous mastitis. PMID- 22305593 TI - Imaging inflammatory breast cancer. AB - Carcinomatous mastitis is a severe form of breast cancer and its diagnosis is essentially clinical and histological. The first examination to perform is still mammography, not only to provide evidence supporting this diagnosis but also to search for a primary intramammary lesion and assess local/regional spread. It is essential to study the contralateral breast for bilaterality. Ultrasound also provides evidence supporting inflammation, but appears to be better for detecting masses and analysing lymph node areas. The role of MRI is debatable, both from a diagnostic point of view and for monitoring during treatment, and should be reserved for selected cases. An optimal, initial radiological assessment will enable the patient to be monitored during neoadjuvant chemotherapy. PMID- 22305594 TI - Breast inflammation: indications for MRI and PET-CT. AB - Breast MRI should not be used for differential diagnosis between inflammatory breast cancer and acute mastitis (AM) prior to treatment. When mastitis symptoms persist after 10 to 15 days of well-managed medical treatment, MRI may be performed in addition to an ultrasound examination, a mammogram and to taking histological samples, in order to eliminate inflammatory breast cancer (IBC). For staging, MRI would seem to be useful in looking for a contralateral lesion, PET CT for finding information about remote metastases and in certain centres, for information about the initial extension to local/regional lymph nodes, which would guide the fields of irradiation (since patients can become lymph node negative after neoadjuvant chemotherapy). MRI and PET-CT seems to be useful for early detection of patients responding poorly to neoadjuvant chemotherapy so that the latter may be rapidly modified. PMID- 22305595 TI - Percutaneous biopsies: indications and techniques. AB - Breast inflammation is a difficult clinical problem as it can result from a variety of causes: specific or non-specific infectious mastitis, which may or may not be complicated, primary or secondary inflammatory mastitis or inflammatory cancer. The main objective of radiology is to eliminate an inflammatory cancer. Other objectives are to characterise an inflammatory condition (where the clinical context is valuable in guiding diagnosis but which often requires a micro- or macrobiopsy) or to obtain a microorganism in cases of complicated infectious mastitis (a diagnostic procedure but also comprising the first stage of treatment). Whether for bacteriological or histological purposes, percutaneous samples therefore play a large part in the diagnostic procedure, other than in the clinical context of pregnancy where mastitis is more easily diagnosed because of its frequency. The guidance method is usually ultrasound, and the needle chosen will depend on the radiological or ultrasound signal: puncture with an 18G needle will be used for a bacteriological sample, microbiopsy of a mass or lymph nodes, or macrobiopsy in the case of microcalcifications. PMID- 22305596 TI - The inflammatory breast: management, decision-making algorithms, therapeutic principles. AB - Inflammatory syndrome is one of the rare emergency breast situations. Its etiology is benign, infectious in most cases. The clinical examination is often self-evident and suggests the diagnosis. But alone it is insufficient, and diagnostic tests are necessary to guide therapy. As essential as it is, mammography's limitations reinforce the benefit of ultrasonography, which in all cases reveals an abscess and has greater sensitivity for detecting a malignant tumor. If the etiology is benign, clinical signs will disappear with medical treatment, with no need for further investigation. While it is legitimate to initiate a trial treatment, it must not delay oncologic management, because of the severity of inflammatory cancer. PMID- 22305597 TI - Shape-controlled fabrication of the porous Co3O4 nanoflower clusters for efficient catalytic oxidation of gaseous toluene. AB - Co(3)O(4) nanoflower clusters were fabricated by a simple low-temperature hydrothermal method. The properties of Co(3)O(4) nanomaterials were comprehensively determined by combining different analytical techniques. The self assembled Co(3)O(4) nanoflower clusters had good crystallinity and porous structure. They were utilized as the catalyst for the degradation of gaseous toluene. The experimental results showed that the catalytic activity of the as prepared Co(3)O(4) nanoflower clusters was much superior to the Co(3)O(4) blocks under the same reaction conditions. PMID- 22305598 TI - Characterization of chitosan/montmorillonite membranes as adsorbents for Bezactiv Orange V-3R dye. AB - The synthesis, characterization and environmental application of chitosan/montmorillonite membrane for adsorption Bezactiv Orange V-3R were investigated. Chitosan/montmorillonite membranes were synthesized in different ratios, containing 10-50% of montmorillonite (MMT) in membrane. These membranes were characterized by using Fourier transform infrared spectroscopy (FTIR), thermogravimetry (TG) and scanning electron microscopy (SEM). The adsorption kinetics were investigated using three different concentrations of Bezactiv Orange dye (30, 50 and 80 mg/L). The adsorption capacity increases with increasing amount of MMT in membranes. These membranes show the highest adsorption capacity when the initial dye concentration was 80 mg/L. The results show that the optimum condition for adsorption of Bezactiv Orange is pH 6. A comparison of kinetic models was evaluated for the pseudo-first and pseudo-second order and intra-particle diffusion. The experimental data were fitted to the pseudo-second order kinetic model, and also followed by intra-particle diffusion. Intra-particle diffusion is not the only rate-controlling step. The Langmuir and Freundlich adsorption isotherms were applied to experimental equilibrium data at different concentration of dye solution. The results indicated the competency of chitosan/MMT membranes adsorbent for Bezactiv Orange adsorption. PMID- 22305599 TI - Bioinspired synthesis of hierarchically micro/nano-structured CuI tetrahedron and its potential application as adsorbent for Cd(II) with high removal capacity. AB - An environment friendly bioinspired strategy for synthesizing hierarchically micro/nano-structured CuI tetrahedron has been developed by combining the stabilization and the reduction performances of l-tryptophan together. A possible growth mechanism of such hierarchical tetrahedron is tentatively proposed. Remarkably, such CuI tetrahedron is found to possess high removal capacity for poisonous Cd(II) ions, 136.3mg/g, and ideal reusability. This is ascribed to the hierarchical micro/nano-structure and chemical adsorption mechanism, which shows great advantages over the traditional nano-scaled adsorbents. These interesting results stand out the promising applications of such hierarchically micro/nano structured materials in environment. It is also a good example for the organic combination of green chemistry and nanotechnologies for the treatment of contaminated water. PMID- 22305600 TI - Scaling of surface-plasma reactors with a significantly increased energy density for NO conversion. AB - Comparative studies revealed that surface plasmas developing along a solid-gas interface are significantly more effective and energy efficient for remediation of toxic pollutants in air than conventional plasmas propagating in air. Scaling of the surface plasma reactors to large volumes by operating them in parallel suffers from a serious problem of adverse effects of the space charges generated at the dielectric surfaces of the neighboring discharge chambers. This study revealed that a conductive foil on the cathode potential placed between the dielectric plates as a shield not only decoupled the discharges, but also increased the electrical power deposited in the reactor by a factor of about forty over the electrical power level obtained without shielding and without loss of efficiency for NO removal. The shield had no negative effect on efficiency, which is verified by the fact that the energy costs for 50% NO removal were about 60 eV/molecule and the energy constant, k(E), was about 0.02 L/J in both the shielded and unshielded cases. PMID- 22305601 TI - Rapid dechlorination of chlorophenols in aqueous solution by [Ni|Cu] microcell. AB - The [Ni|Cu] microcell was prepared by mixing the Ni(0) and Cu(0) particles. The composition and crystal form were characterized by X-ray diffraction (XRD) and scanning electron microscope. The results evidenced the zero-valence metals Ni and Cu were exposed on the surface of particles mixture. The [Ni|Cu] microcell was employed to decompose chlorophenols in aqueous solution by reductive dechlorination. The dechlorination rates of chlorophenols by [Ni|Cu] were >10 times faster than those by [Fe|Cu], [Zn|Cu], [Sn|Cu], and [Fe|Ni] mixtures under the same conditions. [Ni|Cu] is different from other zero valent metals (ZVMs) in that it performed the best at neutral pH. The main products of chlorophenol dechlorination were cyclohexanol and cyclohexanone. The reduction kinetics was between pseudo zero-order and first-order, depending on the pH, concentration, and temperature. These results, combined with electrochemical analysis, suggested that Ni(0) acted as a reductant and catalyst in dechlorination reaction. The H* corridor mechanism from Ni(0) to Cu(0) was also proposed based on hydrogen spillover. The inhibition on the release of Ni(2+) by adding natural organic matters and adjusting pH was investigated. PMID- 22305602 TI - Ignition study of acetone/air mixtures by using laser-induced spark. AB - The breakdown and the laser-induced spark ignition of acetone-air mixtures were experimentally studied using a nanosecond pulse at 1064 nm from a Q-switched Nd:YAG laser. The breakdown was first characterized for different mixtures with acetone and air. This part of the work highlighted the wide variation in the energy absorbed by the plasma during a breakdown. We also demonstrated that the presence of acetone in air tends to reduce the energy required to obtain a breakdown. Next, the ignition of acetone-air mixtures in the equivalence ratio range 0.9-2.4 was investigated. The probabilities of ignition were calculated in function to the laser energy. However, according to the variability of energy absorption by the plasma, we preferred to present the result according to the energy absorbed by the plasma. The minimum ignition energies were also provided. The minimum ignition energy was obtained for an equivalence ratio of 1.6 and an absorbed energy of 1.15 mJ. Finally the characteristics of the plasma (absorption coefficient and kernel temperature) were calculated for the experiments corresponding to minimum ignition energies. PMID- 22305603 TI - Correcting the gas and particle partitioning of PCDD/F congeners in the flue gas of an iron ore sinter plant. AB - This study was aimed at developing an approach for correcting the gas and particle partitioning of PCDD/F congeners for samples collected from the flue gas of an iron ore sinter plant. An iron ore sinter plant equipped with an electrostatic precipitator (EP) and a selective catalytic reduction (SCR) was selected. Flue gas samples were collected at EP inlet, EP outlet and SCR outlet. Both particle- and gas-phase PCDD/Fs were analyzed for each collected sample. PCDD/F contents in EP ashes (EP(ash)) were also analyzed and used to correct the gas and particle partitioning of PCDD/F congeners of the collected flue gas samples. Results show that PCDD/Fs in the flue gas were dominated by the gas phase. Before correction, the removal efficiencies for the gas- and particle phase PCDD/Fs for EP were -58.1% and 64.3%, respectively, and SCR were 39.4% and 83.9%, respectively. The above results were conflict with the expected results for both EP and SCR indicating the need for correcting the gas and particle partitioning of PCDD/F congeners for all collected flue gas samples. After correction, the removal efficiencies become more reasonable for EP (=4.22% and 97.7%, respectively), and SCR (=54.7% and 62.0%, respectively). The above results confirm the effectiveness of the approach developed by this study. PMID- 22305604 TI - Feasibility of flare gas reformation to practical energy in Farashband gas refinery: no gas flaring. AB - A suggested method for controlling the level of hazardous materials in the atmosphere is prevention of combustion in flare. In this work, three methods are proposed to recover flare gas instead of conventional gas-burning in flare at the Farashband gas refinery. These methods aim to minimize environmental and economical disadvantages of burning flare gas. The proposed methods are: (1) gas to liquid (GTL) production, (2) electricity generation with a gas turbine and, (3) compression and injection into the refinery pipelines. To find the most suitable method, the refinery units that send gas to the flare as well as the required equipment for the three aforementioned methods are simulated. These simulations determine the amount of flare gas, the number of GTL barrels, the power generated by the gas turbine and the required compression horsepower. The results of simulation show that 563 barrels/day of valuable GTL products is produced by the first method. The second method provides 25 MW electricity and the third method provides a compressed natural gas with 129 bar pressure for injection to the refinery pipelines. In addition, the economics of flare gas recovery methods are studied and compared. The results show that for the 4.176MMSCFD of gas flared from the Farashband gas refinery, the electricity production gives the highest rate of return (ROR), the lowest payback period, the highest annual profit and mild capital investment. Therefore, the electricity production is the superior method economically. PMID- 22305605 TI - Full-thickness knee articular cartilage defects in national football league combine athletes undergoing magnetic resonance imaging: prevalence, location, and association with previous surgery. AB - PURPOSE: To better define the prevalence and location of full-thickness articular cartilage lesions in elite football players undergoing knee magnetic resonance imaging (MRI) at the National Football League (NFL) Invitational Combine and assess the association of these lesions with previous knee surgery. METHODS: We performed a retrospective review of all participants in the NFL Combine undergoing a knee MRI scan from 2005 to 2009. Each MRI scan was reviewed for evidence of articular cartilage disease. History of previous knee surgery including anterior cruciate ligament reconstruction, meniscal procedures, and articular cartilage surgery was recorded for each athlete. Knees with a history of previous articular cartilage restoration surgery were excluded from the analysis. RESULTS: A total of 704 knee MRI scans were included in the analysis. Full-thickness articular cartilage lesions were associated with a history of any previous knee surgery (P < .001) and, specifically, previous meniscectomy (P < .001) but not with anterior cruciate ligament reconstruction (P = .7). Full thickness lesions were present in 27% of knees with a previous meniscectomy compared with 12% of knees without any previous meniscal surgery. Full-thickness lesions in the lateral compartment were associated with previous lateral meniscectomy (P < .001); a similar relation was seen for medial meniscus tears in the medial compartment (P = .01). CONCLUSIONS: Full-thickness articular cartilage lesions of the knee were present in 17.3% of elite American football players at the NFL Combine undergoing MRI. The lateral compartment appears to be at greater risk for full-thickness cartilage loss. Previous knee surgery, particularly meniscectomy, is associated with these lesions. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 22305606 TI - Frequency dependence of images in scanning laser source technique for a plate. AB - Defect imaging using scanning laser source technique has been investigated for a plate with rounded defects and notch-type defects in our previous studies. This paper examines frequency dependence of the defect images with both calculations and experiments in order to acquire clearer images. Both calculation and experimental results for a straight notch revealed that clearer images of notch type defects can be obtained in the range of low frequency-thickness product below about 200 kHz mm. Moreover, images of the defects of various shapes were obtained by synthesizing images from eight receiving transducers, and similarly to the case of the straight notches, they became more clearly in the low frequency range. PMID- 22305608 TI - The factors associated with preferences for napping and drinking coffee as countermeasures for sleepiness at the wheel among Japanese drivers. AB - OBJECTIVE: We explored differences between professional and non-professional drivers in terms of the factors associated with preferences for generally accepted, effective countermeasures for sleepiness at the wheel--i.e., napping and drinking coffee. METHODS: We performed a cross-sectional questionnaire survey. Data from professional (n = 716) and non-professional (n = 3365) drivers were used for analyses. RESULTS: The results showed that professional drivers experienced drowsy driving and traffic accidents due to falling asleep more often than non-professional drivers. Multiple logistic regression analyses showed that variables which may act as aggravating factors for sleepiness (i.e., engagement in shift-work and insufficient sleep) were associated with preferences for these countermeasures among non-professional drivers. In contrast, among professional drivers, being male and having experienced traffic accidents due to drowsy driving were associated with a preference for napping, while longer annual driving distances and shorter periods after the acquisition of driving licenses were associated with drinking coffee. CONCLUSION: Our results suggest that non professional drivers are likely to take these effective countermeasures when they feel or have the potential to experience sleepiness at the wheel. However, this tendency was not observed in professional drivers, and it is speculated that they do not use naps as a countermeasure until they have experienced traffic accidents due to drowsy driving. Sleep education for professional drivers and their employers is desirable for preventing drowsy driving-related traffic accidents. PMID- 22305607 TI - A new eye on NLR proteins: focused on clarity or diffused by complexity? AB - The nucleotide-binding domain leucine-rich repeat proteins (NLRs) represent the major class of intracellular innate immune receptors in plants and animals. Understanding their functions is a major challenge in immunology. This review highlights recent efforts toward elucidating NLR functions in human and plants. We compare unconventional aspects of NLR proteins across the two kingdoms. We review recent advances describing P-loop independent activation, nuclear cytoplasmic trafficking, oligomerization and multimerization requirements for signaling, and for expanded functions beyond pathogen recognition by several NLR proteins. PMID- 22305609 TI - Association of sleep duration with untreated diabetes in Japanese men. AB - OBJECTIVE: We assessed the cross-sectional association between sleep duration and untreated diabetes in Japanese men. METHODS: Participants included 20,744 men aged 30-64 years who first visited the general hospital in Tokyo for routine health assessments during 2003-2007. Untreated diabetes was defined as not being under diabetes treatment and fasting blood glucose of >=126 mg/dL or hemoglobin A(1c) of >=6.5%. Sleep duration (<=5, 6, 7, or >=8 h) and confounders were assessed using a questionnaire. Logistic regression was used to calculate odds ratios (ORs) for diabetes after adjustment for confounders. RESULTS: The prevalence of untreated diabetes was 3.4% in all men. The prevalence of untreated diabetes by sleep duration was as follows: <=5 h: 3.5%; 6 h: 3.3%; 7 h: 3.2%; and >=8 h: 5.1%. Men who reported sleeping for <=5 h (OR: 1.52, 95% confidential interval [CI]: 1.22-1.90) and >=8 h (OR: 1.39, 95% CI: 1.05-1.85) were significantly more likely to have untreated diabetes compared with those who reported sleeping for 7 h. In stratified analyses by obesity (body mass index >=25.0 kg/m(2)), the association between long sleep duration (>=8 h) and untreated diabetes remained significant only in obese men. CONCLUSION: Short sleep duration was significantly associated with untreated diabetes in both nonobese and obese men. Regarding long sleep duration, a significant association was observed in obese men only. PMID- 22305610 TI - Genomic analyses of gas (nitric oxide and carbon monoxide) and small molecule transmitter (acetylcholine, glutamate and GABA) signaling systems in Daphnia pulex. AB - Diffusible gasses and small molecule transmitters are classes of compounds used by neurons and other cell types for local and hormonal signaling. In crustaceans, there is evidence for the neuronal production of the gasses nitric oxide (NO) and carbon monoxide (CO), as well as the small molecule transmitters acetylcholine, glutamate and GABA. While much is known about the physiological roles played by these molecules in crustaceans, little is known about them at the molecular level. Here, we have mined the genome of Daphnia pulex for genes encoding the biosynthetic enzymes, receptors and transporters necessary for establishing each of these transmitter systems. The biosynthetic enzyme genes identified included nitric oxide synthase, heme oxygenase, choline acetyltransferase, glutaminase and glutamic acid decarboxylase. Genes encoding several transporters (e.g. vesicular acetylcholine transporter) were also characterized, as were ones involved in transmitter degradation/recycling (e.g. acetylcholine esterase); genes encoding receptors for NO and CO (i.e. soluble guanylyl cyclase), and for each small molecule transmitter (both ionotropic and metabotropic receptors for each compound) were identified. These data provide the first molecular descriptions of gas and small molecule transmitter signaling systems in D. pulex, and provide frameworks for future molecular, anatomical and physiological investigations of them in Daphnia. PMID- 22305612 TI - Recent advances in hypoxia-inducible factor (HIF)-1 inhibitors. AB - Tumor hypoxia has been recognized as a common feature of solid tumors and a negative prognostic factor for response to treatment and survival of cancer patients. The discovery of hypoxia-inducible factor-1 (HIF-1), a molecular determinant of responses to hypoxia in mammalian cells, has renewed enthusiasm for discovery and development of targeted therapies exploiting the hypoxic tumor microenvironment. HIF-1 activity in tumors depends on availability of the HIF 1alpha subunit, the levels of which increase under hypoxic conditions and through activation of oncogenes and/or inactivation of tumor suppressor genes. Increased HIF-1 has been correlated with increased angiogenesis, aggressive tumor growth, and poor patient prognosis, leading to current interest in HIF-1 as promising anticancer drug target. In spite of an ever increasing number of putative small molecule inhibitors of HIF-1, only a few are progressing through preclinical and early clinical development. In this review, we will discuss recent advances in discovery and development of small molecule inhibitors that target the HIF-1 pathway as potential anticancer agents. PMID- 22305611 TI - Inflammatory biomarkers as predictors of hospitalization and death in community dwelling older adults. AB - Individuals with multimorbidity may be at increased risk of hospitalization and death. Comorbidity indexes do not capture severity of illness or healthcare utilization; however, inflammation biomarkers that are not disease-specific may predict hospitalization and death in older adults. We sought to predict hospitalization and mortality of older adults using inflammation biomarkers. From a prospective, observational study, 370 community-dwelling adults 65 years or older from central Alabama participated in an in-home assessment and provided fasting blood samples for inflammation biomarker testing in 2004. We calculated an inflammation summary score (range 0-4), one point each for low albumin, high C reactive protein, low cholesterol, and high interleukin-6. Utilizing Cox proportional hazards models, inflammation summary scores were used to predicted time to hospitalization and death during a 4-year follow up period. The mean age was 73.7 (+/-5.9 yrs), and 53 (14%) participants had summary scores of 3 or 4. The rates of dying were significantly increased for participants with inflammation summary scores of 2, 3, or 4 (hazard ratio (HR) 2.22, 2.78, and 7.55, respectively; p<0.05). An inflammation summary score of 4 significantly predicted hospitalization (HR 5.92, p<0.05). Community-dwelling older adults with biomarkers positive for inflammation had increased rates of being hospitalized or dying during the follow up period. Assessment of the individual contribution of particular inflammation biomarkers in the prediction of health outcomes in older populations and the development of validated summary scores to predict morbidity and mortality are needed. PMID- 22305613 TI - Synthesis, anti-HBV activity and renal cell toxicity evaluation of mixed phosphonate prodrugs of adefovir. AB - A series of phosphonate ester prodrugs of adefovir incorporating l-amino (thio)acid and non-steroidal anti-inflammatory drug (NSAID) moieties were synthesized and their anti-HBV activity and renal cell toxicity were evaluated in HepG2 2.2.15 and HK-2 cells respectively. Bioactivity evaluation results revealed that this kind of adefovir prodrug have lower renal cell toxicity than adefovir dipivoxil. Compounds 8a and 8b, incorporating the NSAID ketoprofen and the l amino acid (Val or Ile) structural fragments, exhibited more potent anti-HBV activity than adefovir dipivoxil with IC(50) = 0.51 and 0.73 MUM, SI = 1697.64 and 881.92 respectively. In vitro stability studies showed that the synthesized prodrugs have higher chemical and plasma stability than the positive control adefovir dipivoxil. PMID- 22305614 TI - Synthesis of novel 2-mercapto benzothiazole and 1,2,3-triazole based bis heterocycles: their anti-inflammatory and anti-nociceptive activities. AB - A focused library of novel bis-heterocycles encompassing 2-mercapto benzothiazole and 1,2,3-triazoles were synthesized using click chemistry approach. The synthesized compounds have been tested for their anti-inflammatory activity by using biochemical cyclooxygenase (COX) activity assays and carrageenan-induced hind paw edema. Among the tested compounds, compound 4d demonstrated a potent selective COX-2 inhibition with COX-2/COX-1 ratio of 0.44. Results from carrageenan-induced hind paw edema showed that compounds 4a, 4d, 4e and 4f posses significant anti-inflammatory activity as compared to the standard drug Ibuprofen. The compounds showing significant activity were further subjected to anti-nociceptive activity by writhing test. These four compounds have shown comparable activity with the standard Ibuprofen. Further ulcerogenic studies shows that none of these compounds causing gastric ulceration. PMID- 22305615 TI - Mcl-1 determines the imiquimod-induced apoptosis but not imiquimod-induced autophagy in skin cancer cells. AB - BACKGROUND: Imiquimod had been shown to induce apoptosis and autophagy in several skin cancer cells, especially basal cell carcinoma (BCC) cells. OBJECTIVE: We evaluate the molecular mechanisms of imiquimod-induced apoptosis and autophagy in skin cancer cell lines. METHODS: The Mcl-1, Bcl-2 and Bcl-xL proteins were determined by immunoblotting. The Mcl-1 mRNA level was examined by RT-PCR and real-time PCR. The mechanisms of imiquimod-induced decrease in Mcl-1 protein were evaluated by addition of cycloheximide, MG132 proteasome inhibitor or pan-caspase inhibitor. The phosphorylation of eIF4E, 4E-BP1 and eEF2 in imiquimod treated cells were examined by immunoblotting. The imiquimod-induced apoptosis and autophagy were evaluated in Mcl-1-overexpressing cells by XTT test, mitochondrial membrane potential measurement, DNA content assay, LC3 immunoblotting, EGFP-LC3 puncta formation and quantification of acidic vesicular organelle with acridine orange staining. RESULTS: The decrease in the Mcl-1 protein level was faster and stronger than the decrease in Bcl-2 and Bcl-xL in imiquimod-treated skin cancer cells. The imiquimod-induced decrease in Mcl-1 protein was not caused by blocked transcription or the promotion of degradation but was associated with inactivation of translation factors in BCC cells. The Mcl-1-overexpressing BCC cells were more resistant to intrinsic cellular apoptosis than control BCC cells during imiquimod treatment. Mcl-1 overexpression in BCC cells resulted in the basal activation of autophagy but did not modulate imiquimod-induced autophagy or rescue imiquimod-induced autophagic cell death in BCC cells. CONCLUSIONS: Imiquimod may rapidly downregulate Mcl-1 protein levels by inhibiting translation in skin cancer cells. Mcl-1 may act to protect against apoptosis but not autophagy and autophagic cell death during imiquimod treatment in skin cancer cells. PMID- 22305616 TI - Inflammatory response of human keratinocytes triggered by Sporothrix schenckii via Toll-like receptor 2 and 4. PMID- 22305617 TI - Spectroscopic evidence of abnormal structure of psoriasis vulgaris stratum corneum. PMID- 22305618 TI - [Lung cancer in adults: Better prognosis of patients aged 45 and under related to good condition and lower TNM stage (a comparative and retrospective study)]. AB - BACKGROUND: Bronchogenic carcinoma (BC) is a worldwide health public problem with a parallel but delayed development to smoking. The prognosis of BC in young patients is poorly known mainly because of few studies that have looked at this group of patients. The hypothesis of our study is that 'young' patients with BC have a better prognosis than others. METHODS: We conducted a retrospective epidemiologic study of all patients aged 45 and under (n=73) followed for BC between 2002 and 2007 in two hospitals in the central region in France, compared with patients over 45 years random (n=73). We evaluated the clinical characteristics (sex, smoking habits, WHO status, clinical presentation, histology, TNM stage), the management and prognosis of these patients. RESULTS: The median survival of patients aged 45 and under was 13.4 months against 8.9 months for patients over 45 years. In multivariate analysis, age is not an independent prognostic factor (P=0.41) in contrast to the WHO status (P=0.002) and initial TNM stage (P<0.001). There was no significant difference for other clinical characteristics between the two patient populations. CONCLUSION: In our study, the better prognosis of the "young" patient group is not directly related to age but in good condition and lower TNM stage of these patients. PMID- 22305619 TI - Ultra-deep sequencing of HIV-1 reverse transcriptase before start of an NNRTI based regimen in treatment-naive patients. AB - There are conflicting data on the impact of low frequency HIV-1 drug-resistant mutants on the response of first-line highly active antiretroviral therapy (HAART), more specifically containing a NNRTI. As population sequencing does not detect resistant viruses representing less than 15-25% of the viral population, more sensitive techniques have been developed but still need clinical validation. We evaluated ultra-deep sequencing (UDPS), recently more available and affordable, as a tool for the detection of HIV-1 minority species carrying drug resistant mutation (DRM) in a clinical setting. A retrospective analysis of the reverse transcriptase (RT) gene of plasma HIV-1 from 70 patients starting a NNRTI based regimen was performed. Minority populations were defined as representing > 1% and < 20% of the total viral population. Using UDPS, we could not confirm an association between the presence of low minority variants harbouring RT mutations at the start of therapy and primary or secondary therapeutic failure. PMID- 22305620 TI - An intermediate dose of LCMV clone 13 causes prolonged morbidity that is maintained by CD4+ T cells. AB - Wasting is a sign of various underlying disorders and is a common feature of cancer, sepsis, and AIDS. We have developed an in vivo model to study the various stages of wasting following infection of mice with lymphocytic choriomeningitis virus cl-13. Using this model we have identified four distinct stages of wasting and have discovered that all stages occur in the different groups of mice regardless of whether the virus is cleared or persists. However, the degree and extent of wasting vary between groups of mice, depending upon the dose of virus administered. Blocking IFNgamma or TNFalpha, which are believed to take part in the wasting process, did not affect the wasting state. Finally, we found that CD4+ T cells control the maintenance stage of wasting. We believe this model will be useful in studying the regulation of wasting during a persistent viral infection, hopefully leading to improved therapies to ameliorate the disorder. PMID- 22305621 TI - Activation of Oas1a gene expression by type I IFN requires both STAT1 and STAT2 while only STAT2 is required for Oas1b activation. AB - The murine 2'-5' oligoadenylate synthetase 1a (Oas1a) and Oas1b genes are type 1 IFN responsive genes. Oas1a is an active synthetase with broad antiviral activity mediated through RNase L. Oas1b is inactive but can inhibit Oas1a synthetase activity and mediate a flavivirus-specific antiviral activity through an unknown RNase L-independent mechanism. Analysis of promoter elements regulating gene transcription confirmed that an IFN-stimulated response element (ISRE) is required for IFN beta-activation but neither the overlapping IRF binding site present in both promoters nor the adjacent Oas1b NF-kappa B site is required. Mutation of the overlapping STAT site negatively affected IFN beta-induction of Oas1a but not of Oas1b. Also, IFN beta induction of Oas1a was STAT1- and STAT2 dependent, while induction of Oas1b was STAT1-independent but STAT2-dependent. The two promoters differ at a single nucleotide in the STAT site. The data indicate that these two duplicated genes can be differentially regulated by IFN beta. PMID- 22305622 TI - Type 1 IFN-independent activation of a subset of interferon stimulated genes in West Nile virus Eg101-infected mouse cells. AB - Although infection of mouse embryofibroblasts (MEFs) with WNV Eg101 induced interferon (IFN) beta production and STAT1 and STAT2 phosphorylation, these transcription factors (TFs) were not detected in the nucleus or on the promoters of four IRF-3-independent interferon stimulated genes (ISGs): Oas1a and Irf7 (previously characterized as IFN/ISGF3-dependent), Oas1b and Irf1. These ISGs were upregulated in WNV Eg101-infected STAT1-/-, STAT2-/-, and IFN alpha/beta receptor-/- MEFs. Although either IRF-3 or IRF-7 could amplify/sustain Oas1a and Oas1b upregulation at later times after infection, these factors were not required for the initial gene activation. The lack of upregulation of these ISGs in WNV Eg101-infected IRF-3/9-/- MEFs suggested the involvement of IRF-9. Activation of Irf1 in infected MEFs did not depend on any of these IRFs. The data indicate that additional alternative activation mechanisms exist for subsets of ISGs when a virus infection has blocked ISG activation by the canonical IFN mediated pathway. PMID- 22305623 TI - Kotonkan and Obodhiang viruses: African ephemeroviruses with large and complex genomes. AB - Kotonkan virus (KOTV) and Obodhiang virus (OBOV) are rhabdoviruses that were isolated from arthropods in Africa and formerly classified as lyssaviruses. KOTV causes clinical bovine ephemeral fever in cattle; the ecology and pathogenicity of OBOV is poorly understood. In this paper, we report the complete genome sequences of KOTV and OBOV, their gene expression profiles, and their serological and phylogenetic relationships to other rhabdoviruses. The 15,870 nt KOTV genome (3'-l-N-P-M-G-G(NS)-alpha1-alpha2-beta-gamma-delta-L-t-5') is similar to that of bovine ephemeral fever virus but encodes an additional protein (delta) that shares homology with the pleckstrin homology domain of coactivator-associated arginine methyltransferase. The 14,717 nt OBOV genome (3'-l-N-P-M-G-G(NS)-alpha1 alpha2-beta-L-t-5') is similar to that of Adelaide River virus from which it is distinguishable serologically. In each virus, all ORFs, except alpha1 and alpha2, are transcribed as monocistronic mRNA. Genetic and serological data indicate that KOTV and OBOV should be classified as new species in the genus Ephemerovirus. PMID- 22305624 TI - Rhesus cytomegalovirus encodes seventeen microRNAs that are differentially expressed in vitro and in vivo. AB - Human cytomegalovirus (HCMV) miRNAs are important for regulation of viral infection and evasion of host immune responses. Unfortunately, the importance of HCMV miRNAs cannot be addressed in vivo due to the species specificity of CMVs. Rhesus CMV (RhCMV) infection of rhesus macaques provides an important model system for HCMV pathogenesis due to the genetic similarity between the viruses. In this report, seventeen RhCMV miRNAs were identified using Next Generation Sequencing. In fibroblasts, RhCMV miRNAs associate with Argonaute proteins and display several patterns of expression, including an early peak in expression followed by decline and accumulation throughout infection. Additionally, RhCMV encodes an HCMV miR-US5-2 homologue that targets the 3' UTR of RhCMV US7. Finally, examination of salivary gland tissue from infected animals revealed the presence of a subset of viral miRNAs. This study highlights the importance of the RhCMV model system for evaluating the roles of CMV miRNAs during viral infection. PMID- 22305625 TI - Factors influencing unexpected disposition after orthopedic ambulatory surgery. AB - STUDY OBJECTIVE: To analyze whether patient characteristics, ambulatory facility type, anesthesia provider and technique, procedure type, and temporal factors impact the outcome of unexpected disposition after ambulatory knee and shoulder surgery. DESIGN: Retrospective analysis of a national database. SETTING: Freestanding and hospital-based ambulatory surgery facilities. MEASUREMENTS: Ambulatory knee and shoulder surgery cases from 1996 and 2006 were identified through the National Survey of Ambulatory Surgery. The incidence of unexpected disposition status was determined and risk factors for such outcome were analyzed. MAIN RESULTS: Factors independently increasing the risk for unexpected disposition included procedures performed in hospital-based versus freestanding facilities [odds ratio (OR) 6.83 (95% confidence interval [CI] 4.34; 10.75)], shoulder versus knee procedures [OR 3.84 (CI 2.55; 5.77)], anesthesia provided by nonanesthesiology professionals and certified registered nurse-anesthetists versus anesthesiologists [OR 7.33 (CI 4.18; 12.84) and OR 1.80 (CI 1.09; 2.99), respectively]. Decreased risk for unexpected disposition was for procedures performed in 2006 versus 1996 [OR 0.15 (CI 0.10; 0.24)] and the use of anesthesia other than regional or general [OR 0.34 (CI 0.18; 0.68)]. CONCLUSIONS: The decreased risk for unexpected disposition associated with more recent data and with freestanding versus hospital-based facilities may represent improvements in efficiency, while the decreased odds for such disposition status associated with the use of other than general or regional anesthesia may be related to a lower invasiveness of cases. We found an increased risk of adverse disposition in cases where the anesthesia provider was a nonanesthesiology professional. No difference in this outcome was noted when an anesthesia care team provided care. PMID- 22305626 TI - Transperineal template-guided prostate biopsy for patients with persistently elevated PSA and multiple prior negative biopsies. AB - OBJECTIVE: To evaluate the use of transperineal template-guided prostate biopsy for patients with persistently elevated PSA despite multiple negative prior biopsies. MATERIALS AND METHODS: A retrospective review was performed of patients with at least two prior prostate biopsies who underwent transperineal template guided biopsy. Electronic medical records were reviewed to obtain relevant clinical, laboratory, and pathologic data. RESULTS: A total of 34 patients underwent transperineal template-guided biopsy. Patients had a mean of 3.7 +/- 1.6 (range 2-8) prior biopsies, including prior negative transurethral resection (TUR) biopsy in 6 (17.6%) patients. Prostate cancer was detected in 17 (50%) of the 34 patients. Of these, 14 (82.4%) patients had cancer in the anterior prostate, 9 (52.9%) patients had cancer in the apical prostate, and 16 (94.1%) patients had cancer in either the anterior or apical prostate. Gleason score was 3+3 in 9 (52.9%) patients and 3+4 or greater in 7 (47.1%) patients. The mean number of positive cores was 4.5 +/- 3.0 (range 1-11). Of the 17 patients with a diagnosis of cancer, 7 underwent radical prostatectomy, 7 underwent radiation therapy, 1 elected active surveillance, and 1 was deciding between surgery and radiation therapy; 1 patient received palliative chemotherapy for synchronous metastatic pancreatic carcinoma. Patients in whom cancer was detected had significantly smaller prostate volume, higher PSA, higher PSA density, and greater PSA velocity. CONCLUSIONS: Transperineal template-guided prostate biopsy is an effective technique for detecting cancer in patients with persistently elevated PSA despite multiple negative biopsies. It improves sampling of the anterior and apical prostate, and should be included as part of the diagnostic algorithm to reduce extensive repeat biopsy. PMID- 22305627 TI - Rationing in urologic oncology: lessons from sipuleucel-T for advanced prostate cancer. AB - OBJECTIVES: As complex novel cancer drugs are developed, supply may transiently fail to meet demand as production capacity established for research purposes is scaled up to meet anticipated clinical volume. There are no clear guidelines for how clinicians and medical centers should allocate scarce cancer care resources among patients who may benefit from the intervention. MATERIALS AND METHODS: We describe a recent scenario in which demand exceeded supply for a novel immunotherapy, sipuleucel-T, that was newly approved by the FDA for castration resistant prostate cancer. Production of this autologous cellular therapy was initially limited to one facility with supply projected to serve only 2,000 out of approximately 30,000 potentially eligible patients in the United States. RESULTS AND CONCLUSIONS: We propose basic guidelines that should be followed when allocating scarce cancer therapies and highlight ongoing challenges that must be resolved both with regard to rationing cancer care and with regard to access to high cost novel interventions in oncology in general. PMID- 22305628 TI - Effects of acute postoperative pain on catecholamine plasma levels, hemodynamic parameters, and cardiac autonomic control. AB - Postoperative pain is often stated to be a significant contributor to a sympathetic stress response after surgery. However, hardly any evidence has been published to support this assumption. Hence it was the aim of this trial to investigate the relationship between postoperative pain and hemodynamic, endocrine, and autonomic parameters. A total of 85 postoperative patients in the recovery room were repeatedly asked to rate their pain on a numeric rating scale (NRS). Concurrently, the parameters of heart rate variability (HRV) were analysed, and mean arterial pressure (MAP), heart rate (HR) and respiration rate (RR) were recorded. Pain was categorized into no, mild, moderate, and severe. Blood samples were taken for epinephrine (EPI) and norepinephrine (NE) plasma level assessment at the time of recovery room admission and discharge, and each time pain was found decreased in categorized severity. A total of 239 pain readings were obtained. None of the investigated parameters correlated with NRS scores. NE was higher at NRS 5 to 10 vs. NRS 0 to 4 (mean [SEM]: 1009 [73] pg/mL vs. 872 [65] pg/mL; P<0.01). This was also found for MAP, but not for EPI or the parameters of HRV, HR, and RR. In contrast to common belief, the severity of postoperative pain does not appear to be associated with the degree of sympathetic stress response after surgery, and other factors such as surgical trauma may be more important. Importantly, the absence of signs of sympathetic stimulation cannot be seen as a guarantee for the absence of significant pain. PMID- 22305629 TI - mRNA expression of 5-hydroxytryptamine 1B, 1D, and 1F receptors and their role in controlling the release of calcitonin gene-related peptide in the rat trigeminovascular system. AB - Triptans, a family of 5-hydroxytryptamine (5-HT) 1B, 1D, and 1F receptor agonists, are used in the acute treatment of migraine attacks. The site of action and subtypes of the 5-HT(1) receptor that mediate the antimigraine effect have still to be identified. This study investigated the mRNA expression of these receptors and the role of 5-HT(1) receptor subtypes in controlling the release of calcitonin gene-related peptide (CGRP) in rat dura mater, trigeminal ganglion (TG), and trigeminal nucleus caudalis (TNC). The mRNA for each receptor subtype was quantified by quantitative real-time polymerase chain reaction. A high potassium concentration was used to release CGRP from dura mater, isolated TG, and TNC in vitro. The immunoreactive CGRP (iCGRP) release was measured by enzyme linked immunoassay. The mRNA transcripts of the 3 5-HT(1) receptor subtypes were detected in the trigeminovascular system. Sumatriptan inhibited iCGRP release by 31% in dura mater, 44% in TG, and 56% in TNC. This effect was reversed by a 5 HT(1B/1D) antagonist (GR127395). The 5-HT(1F) agonist (LY-344864) was effective in the dura mater (26% iCGRP inhibition), and the 5-HT(1D) agonist (PNU-142633) had a significant effect in the TNC (48%), whereas the 5-HT(1B) agonist (CP 94253) was unable to reduce the iCGRP release in all tissues studied. We found that sumatriptan reduced the iCGRP release via activation of 5-HT(1D) and 5 HT(1F) receptor subtypes. The 5-HT(1F) receptor agonist was effective only in peripheral terminals in dura mater, whereas the 5-HT(1D) agonist had a preferential effect on central terminals in the TNC. PMID- 22305630 TI - Reliability of the visual analog scale in children with acute pain in the emergency department. AB - In children, many psychometric properties of the visual analogue scale (VAS) are known, including the minimum clinically significant difference (10mm on a 100-mm VAS). However, its imprecision or reliability is not well known. Thus, in order to determine the reliability of this scale, a prospective cohort study was performed in patients aged 8-17 years presenting to a pediatric emergency department with acute pain. Pain was graded 4 times using a paper VAS (0-100mm): T(0), T(3), T(6), and T(>= 36)minutes. After T(6), patients were asked if their pain had changed since T(0)minute. The primary analysis was the repeatability coefficient of the VAS, determined according to the Bland-Altman method for measuring agreement using repeated measures in patients reporting that their pain was the same for T(0), T(3), and T(6). In order to appropriately estimate the within-subject SD, 96 patients were required if we obtained 3 measurements for each patient. A total of 151 patients with a mean age of 12.2 +/- 2.5 years were enrolled. Among them, 100 mentioned that their pain was the same for T(0), T(3), and T(6)minutes. The repeatability coefficient of the VAS for these children was 12 mm when the pain did not change. This implies that, for a child, all pain intensity measurements within 12 mm should be considered the same pain intensity on a paper VAS. This measure should also be evaluated on other types of VAS. PMID- 22305631 TI - Long term respiratory outcomes of congenital thoracic malformations. AB - The advent of universal antenatal ultrasonography in many countries has revealed the full spectrum of congenital thoracic malformations (CTMs) and presented clinicians with a number of practical dilemmas to do with diagnosis and management. We present a review of the most common forms of CTMs, including congenital cystic adenomatoid malformation, bronchopulmonary sequestration, and lobar and segmental emphysema. PMID- 22305632 TI - Lipid-altering efficacy and safety profile of co-administered extended release niacin/laropiprant and simvastatin versus atorvastatin in patients with mixed hyperlipidemia. AB - BACKGROUND: Extended-release niacin/laropiprant (ERN/LRPT) reduces flushing and preserves the lipid-modifying effects of ERN. This study compared the efficacy and safety of ERN/LRPT plus simvastatin (ERN/LRPT+SIMVA) with atorvastatin (ATORVA) in patients with mixed hyperlipidemia. METHODS: After a 4-week placebo run-in, 2340 patients (LDL-C >= 130 and <= 190 mg/dL, TG >= 150 and <= 500 mg/dL and above NCEP ATP III risk-based LDL-C goal) were randomized to 1 of 6 treatment arms: ERN/LRPT 1g/20mg+SIMVA (10 or 20mg), or ATORVA (10, 20, 40, or 80 mg) once daily. RESULTS: At Week 12, ERN/LRPT+SIMVA was superior to ATORVA in decreasing LDL-C/HDL-C (primary endpoint) at each pre-specified dose comparison: ERN/LRPT+SIMVA 20mg vs. ATORVA 10mg (-13.2%; p<0.001); ERN/LRPT+SIMVA 40 mg vs. ATORVA 20mg (-10.8%; p<0.001); ATORVA 40 mg (-5.1%; p<0.001); and ATORVA 80 mg ( 4.2%; p=0.007). At Week 12, ERN/LRPT+SIMVA was superior to ATORVA in increasing HDL-C and reducing TG for all pre-specified treatment comparisons, and reducing non-HDL-C and LDL-C for the ERN/LRPT+SIMVA 20mg versus ATORVA 10mg and ERN/LRPT+SIMVA 40 mg versus ATORVA 20-mg dose comparisons, but not the ERN/LRPT+SIMVA 40 mg versus ATORVA 40- and 80-mg dose comparisons. Adverse experiences (AEs) typically associated with niacin (flushing, pruritus, increased glucose, increased uric acid) were more common with ERN/LRPT+SIMVA, and hepatic related laboratory AEs were more common with ATORVA. CONCLUSION: ERN/LRPT+SIMVA was generally superior to ATORVA in improving lipid parameters after 12 weeks and was generally well tolerated in patients with mixed hyperlipidemia. PMID- 22305633 TI - IgM-phosphorylcholine autoantibodies and outcome in acute coronary syndromes. AB - BACKGROUND: Antibodies against proinflammatory phosphorylcholine (anti-PC) seem to be protective and reduce morbidity. We sought to determine whether low levels of immunoglobulin-M (IgM) autoantibodies against PC add prognostic information in acute coronary syndromes (ACS). METHODS: IgM anti-PC titers were measured in serum obtained within 24h of admission from 1185 ACS patients (median age 66 years, 30% women). We evaluated major acute cardiovascular events (MACE) and all cause mortality short--(6 months), intermediate--(18 months) and long--(72 months) terms. RESULTS: Low anti-PC titers were associated with MACE and all cause mortality at all follow-up times. After adjusting for clinical variables, plasma troponin-I, proBNP and CRP levels, associations remained at all times with MACE, short and intermediate terms also with all-cause mortality. With anti-PC titers below median, adjusted hazard ratios at 18months were for MACE 1.79 (95% confidence interval [CI]: 1.31 to 2.44; p=0.0002) and for all-cause mortality 2.28 (95% CI: 1.32 to 3.92; p=0.003). Anti-PC and plasma CRP were unrelated and added to risk prediction. CONCLUSIONS: Serum IgM anti-PC titers provide prognostic information above traditional risk factors in ACS. The ease of measurement and potential therapeutic perspective indicate that it may be a valuable novel biomarker in ACS. PMID- 22305634 TI - Anthropometric measures and vagal indexes of heart rate variability in a population with a high prevalence of Chagas disease--differences according to obesity status. PMID- 22305635 TI - [Intravascular large B cell lymphoma: a case series of three patients and update]. AB - PURPOSE: Intravascular large B cell lymphoma (IVLBCL) is a rare and aggressive variant of non-Hodgkin's lymphoma, characterized by multifocal proliferation of lymphoma cells exclusively within small and medium blood vessels. IVLBCL can be systemic and quite polymorphic, which often makes it difficult to diagnose, thus delaying appropriate treatment. PATIENTS AND METHODS: We report three patients of atypical IVLBCL, through the study of which we overview recent knowledge about IVLBCL. RESULTS: The first patient initially presented with peripheral thrombocytopenia and splenic destruction of platelets, later completed with an interstitial pulmonary syndrome. The second patient, of African origin, we believe is the first case of a black patient with IVLBCL described in the medical literature. The third belongs to the rare group of occidental patients that present an IVLBCL associated with a hemophagocytic syndrome. CONCLUSION: Intravascular large B cell lymphoma is a systemic and polymorphic disease. Awareness of this entitiy should allow rapid and appropriate management. PMID- 22305636 TI - Binding of beta-amyloid to sulfated sugar residues in a polymer brush. AB - A glycopolymer obtained by living radical polymerization of glucose-carrying vinyl monomer was sulfated and accumulated as a polymer brush on a gold colloid immobilized glass. Binding processes of various proteins to sulfated glucose residues in the brush were examined by the increase in absorbance with a help of localized surface plasmon resonance. beta-Amyloid protein (Abeta) bound to the sulfated glycopolymer brush, whereas no binding to the non-sulfated one. An AFM image of Abeta aggregates on the sulfated brush was ellipsoidal, whereas no shaped aggregation of Abeta on the poly(methacrylic acid) and poly[2 (dimethylamino)ethyl methacrylate] brushes. The present results indicate the importance of balance between electrostatic attraction and repulsion in the folding-aggregation phenomena of Abeta at the surface of glycopolymers. PMID- 22305637 TI - Formulation of amphiphilic drug amitriptyline hydrochloride by polyoxyethylene sorbitan esters in aqueous electrolytic solution. AB - In the present work, the interaction between an antidepressant drug amitriptyline hydrochloride and nonionic polyoxyethylene surfactants, with special attention to the possible contribution from the ion-dipole type of interaction, has been investigated by using multitechnique approach. Tensiometric and conductometric studies show steeper decrease on the critical micellar concentration gradient of the drug in the presence of electrolyte (NaCl) as well as nonionic surfactants. Critical assessments by applying Clint, Rubingh, Rosen, Motomura and other thermodynamic models confirm strong interactions in the mixed monolayer at the surface and in mixed micelle in the bulk of aqueous electrolytic solution. The structural difference in the drug and nonionic surfactants also plays a role in tuning the aggregational behavior of the drug-surfactant mixtures. Finally, it is shown by DLS measurements that the micellar growth of drug-surfactant aggregates is favored in terms of increase in hydrodynamic radii in the presence of electrolyte. However, the nonionic surfactants provide sufficient steric crowding causing dissociation of larger micelles into smaller ones with small radii. PMID- 22305638 TI - Multiwall carbon nanotubes/polycaprolactone composites for bone tissue engineering application. AB - In this study, the multiwall carbon nanotubes (MWNTs)/polycaprolactone composite scaffolds were fabricated by the solution evaporation technique. The morphology, phase composition and the mechanical properties of the composite scaffolds were characterized and the cellular bioactivity of the scaffolds was assessed by using rat bone-marrow-derived stroma cells (BMSCs). The attachment, proliferation and differentiation of the BMSCs on the composite scaffolds were analyzed by scanning electron microscopy (SEM), 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) nuclear staining and fluorescein diacetate (FDA) and propidium iodide (PI) live/dead staining, methylthiazol tetrazolium (MTT) assay and alkaline phosphatase (ALP) activity assay, respectively. Results showed that mechanical properties of the composite scaffolds were improved with the addition of MWNTs (0.25-2 wt%). BMSCs on the composite scaffolds differentiated down the osteogenic lineage and expressed high levels of bone marker ALP. The scaffolds with low concentration (0.5 wt%) of MWNTs can enhance the proliferation and differentiation of the BMSCs more than that with higher concentration of MWNTs. It is concluded that MWNTs/PCL composite scaffolds have the potential for bone tissue engineering and the relatively low concentration of MWNTs (0.5 wt%) is preferred. PMID- 22305639 TI - Almanac 2011: cardiomyopathies. The national society journals present selected research that has driven recent advances in clinical cardiology. AB - As we approach the end of 2011 it is clear that the next few years are going to be dominated by the application of new high throughput genetic screening techniques, capable of screening the entire exome or indeed genome. Understanding the data generated by these techniques will require new and equally sophisticated analysis of large and complex datasets, using a systems biology approach with deeper phenotyping and advanced modelling techniques that have the flexibility for continuous update, refinement with discovery of new knowledge. Exciting new developments that may also transform cardiomyopathy research include those of infrastructure and organisation (multi-centre collaborations) and spin-offs from the field of regenerative medicine research. For clinical researchers that translate this information to the clinic the focus will however remain the same; namely improvement of quality and quantity of life. PMID- 22305640 TI - Degradation of 32 emergent contaminants by UV and neutral photo-fenton in domestic wastewater effluent previously treated by activated sludge. AB - This study focuses on the removal of 32 selected micropollutants (pharmaceuticals, corrosion inhibitors and biocides/pesticides) found in an effluent coming from a municipal wastewater treatment plant (MWTP) based on activated sludge. Dissolved organic matter was present, with an initial total organic carbon of 15.9 mg L(-1), and a real global quantity of micropollutants of 29.5 MUg L(-1). The treatments tested on the micropollutants removal were: UV light emitting at 254 nm (UV(254)) alone, dark Fenton (Fe(2+,3+)/H(2)O(2)) and photo-Fenton (Fe(2+,3+)/H(2)O(2)/light). Different irradiation sources were used for the photo-Fenton experiences: UV(254) and simulated sunlight. Iron and H(2)O(2) concentrations were also changed in photo-Fenton experiences in order to evaluate its influence on the degradation. All the experiments were developed at natural pH, near neutral. Photo-Fenton treatments employing UV(254), 50 mg L(-1) of H(2)O(2), with and without adding iron (5 mg L(-1) of Fe(2+) added or 1.48 mg L(-1) of total iron already present) gave the best results. Global percentages of micropollutants removal achieved were 98 and a 97% respectively, after 30 min of treatments. As the H(2)O(2) concentration increased (10, 25 and 50 mg L(-1)), best degradations were observed. UV(254), Fenton, and photo-Fenton under simulated sunlight gave less promising results with lower percentages of removal. The highlight of this paper is to point out the possibility of the micropollutants degradation in spite the presence of DOM in much higher concentrations. PMID- 22305641 TI - Application of tire chips to reduce the temperature of secondary geomembranes in municipal solid waste landfills. AB - Heat generated by the biodegradation of waste and other chemical processes in a landfill can potentially affect the long-term performance of landfill liner system, in particular that of a high-density polyethylene geomembrane. In a double liner system, the difference in leachate exposure and temperature might improve the long-term performance of the secondary geomembrane compared to that of the primary geomembrane. However, in some cases, the temperature is likely to be high enough to substantially reduce the service-life of the secondary geomembrane. This study explores the possible effectiveness of using tire chips as thermal insulation between primary and secondary liners to reduce the temperature of secondary geomembranes as compared to traditional soil materials. Heat and contaminant migration analyses are performed for cases with no insulation and for cases in which a layer of soil or tire chips has been used as thermal insulation between the primary and secondary liners. The effect of insulation on prolonging the service-life of a secondary geomembrane and, consequently, on contaminant transport through a liner system is examined for the case of a volatile organic compound (dichloromethane) found in landfill leachate. The study suggests that the use of tire chips warrants consideration, however there are other practical issues that require consideration in the detailed design and construction of landfill liners. Issues such as finite service-life, low working temperature, excessive settlement, ability to generate internal heat, leaching of tire chips and limitations in performing electrical resistivity leak detection tests are identified. PMID- 22305642 TI - High rate mesophilic, thermophilic, and temperature phased anaerobic digestion of waste activated sludge: a pilot scale study. AB - The paper reports the findings of a two-year pilot scale experimental trial for the mesophilic (35 degrees C), thermophilic (55 degrees C) and temperature phased (65+55 degrees C) anaerobic digestion of waste activated sludge. During the mesophilic and thermophilic runs, the reactor operated at an organic loading rate of 2.2 kgVS/m(3)d and a hydraulic retention time of 20 days. In the temperature phased run, the first reactor operated at an organic loading rate of 15 kgVS/m(3)d and a hydraulic retention time of 2 days while the second reactor operated at an organic loading rate of 2.2 kgVS/m(3)d and a hydraulic retention time of 18 days (20 days for the whole temperature phased system). The performance of the reactor improved with increases in temperature. The COD removal increased from 35% in mesophilic conditions, to 45% in thermophilic conditions, and 55% in the two stage temperature phased system. As a consequence, the specific biogas production increased from 0.33 to 0.45 and to 0.49 m(3)/kgVS(fed) at 35, 55, and 65+55 degrees C, respectively. The extreme thermophilic reactor working at 65 degrees C showed a high hydrolytic capability and a specific yield of 0.33 g COD (soluble) per gVS(fed). The effluent of the extreme thermophilic reactor showed an average concentration of soluble COD and volatile fatty acids of 20 and 9 g/l, respectively. Acetic and propionic acids were the main compounds found in the acids mixture. Because of the improved digestion efficiency, organic nitrogen and phosphorus were solubilised in the bulk. Their concentration, however, did not increase as expected because of the formation of salts of hydroxyapatite and struvite inside the reactor. PMID- 22305643 TI - Developmental process of musculoskeletal integration in ostracod antenna. AB - The functional morphology of arthropod appendages shows remarkable diversity. Plausible functional integrations, particularly between muscles and the exoskeleton, must be achieved in these diverse morphologies. This study provides an insight into the evolutionary pathway of diversified appendages from a functional point of view. The musculoskeletal structure and development of antennae in five species of Cypridocopina were compared. The muscle and skeletal systems are integrated in several ways: The integration in Propontocypris attenuata occurs during various stages of the molting growth, whereas that in Fabaeformiscandona breuili occurs during the myogenesis. These two types of developmental processes have notable similarities, despite their occurrence during different developmental phases. From the overview of the molecular phylogeny presented by earlier studies, it is suggested that the integrated musculoskeletal system has reappeared repeatedly in cypridoid lineages as an atavism. This study demonstrates how arthropod appendages evolve without losing the integrity of the functional whole. PMID- 22305644 TI - Cigarette smoking, illicit drug use, and routes of administration among heroin and cocaine users. AB - Cigarette smoking is ubiquitous among illicit drug users. Some have speculated that this may be partially due to similarities in the route of administration. However, research examining the relationship between cigarette smoking and routes of administration of illicit drugs is limited. To address this gap, we investigated sociodemographic and drug use factors associated with cigarette smoking among cocaine and heroin users in the Baltimore, Maryland community (N=576). Regular and heavy cigarette smokers were more likely to be White, have a history of a prior marriage, and have a lower education level. Regular smoking of marijuana and crack was associated with cigarette smoking, but not heavy cigarette smoking. Injection use was more common among heavy cigarette smokers. In particular, regular cigarette smokers were more likely to have a lifetime history of regularly injecting heroin. Optimal prevention and treatment outcomes can only occur through a comprehensive understanding of the interrelations between different substances of abuse. PMID- 22305645 TI - Dimensions and severity of marijuana consequences: development and validation of the Marijuana Consequences Questionnaire (MACQ). AB - The Marijuana Consequences Questionnaire (MACQ) is a 50-item self-report measure modeled after the Young Adult Alcohol Consequences Questionnaire (YAACQ). College students (n=315) completed questionnaires online. A confirmatory factor analysis supported the hypothesized 8-factor structure. The results indicate good convergent and discriminant validity of the MACQ. A brief, unidimensional, 21 item version (B-MACQ) was developed by a Rasch model. Comparison of item severity estimates of the B-MACQ items and the corresponding items from the YAACQ indicates that the severity of alcohol- and marijuana-problems is defined by a relatively unique pattern of consequences. The MACQ and B-MACQ provide promising new alternatives to assessing marijuana-related problems. PMID- 22305646 TI - Functional outcomes following revascularisation for critical limb ischaemia. AB - OBJECTIVES: More traditional outcome measures following lower limb bypass procedures are poor predictors of functional outcome. This paper aimed to review the effect of infrainguinal bypass surgery on residential and mobility status in patients with critical limb ischaemia. DESIGN: Review. METHODS: A Medline search up until April 2011 was undertaken of all studies involving patients with CLI undergoing ILLB and PTA. Studies were reviewed if they addressed the ambulatory/residential status of the patients pre- and post-operatively. Ambulatory status was defined as the ability to walk even with the help of a stick/frames. Independent residential status was defined as living at home with no help. RESULTS: A total of 10 studies on IILB were deemed suitable for inclusion in the review, reporting 3381 patients (2064 men). Median age ranged from 66 years to 84 years. Thirty day mortality ranged from 0% to 6.3%. Follow-up ranged from 30 days to 1 year. Three studies noted an improvement in ambulation status. No study reported any improvement in residential status after ILLB. Only one study reported on specific improvements in ambulatory status in patients with CLI after PTA. CONCLUSIONS: ILLB for patients with CLI is not without risk. Patients are not as independent or mobile following surgery. Further studies need to firstly identify the cause(s) of this and to determine optimal methods to return more patients to independence. Furthermore, CLI studies need to routinely report data on functionality. PMID- 22305647 TI - Effects of natural antioxidants in neurodegenerative disease. AB - Polyphenols are secondary metabolites with antioxidant properties and are abundant in the diet. Fruits, vegetables, herbs, and various drinks (tea, wine, and juices) are all sources of these molecules. Despite their abundance, investigations into the benefits of polyphenols in human health have only recently begun. Phenolic compounds have received increasing interest because of numerous epidemiological studies. These studies have suggested associations between the consumption of polyphenol-rich aliments and the prevention of chronic diseases, such as cancer, cardiovascular diseases, and neurodegenerative diseases. More specifically, in the last 10 years literature on the neuroprotective effects of a polyphenol-rich diet has grown considerably. It has been demonstrated, in various cell culture and animal models, that these metabolites are able to protect neuronal cells by attenuating oxidative stress and damage. However, it remains unclear as to how these compounds reach the brain, what concentrations are necessary, and what biologically active forms are needed to exert beneficial effects. Therefore, further research is needed to identify the molecular pathways and intracellular targets responsible for polyphenol's neuroprotective effects. The aim of this paper is to present various well-known dietary polyphenols and their mechanisms of neuroprotection with an emphasis on Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. PMID- 22305648 TI - Alterations of PI3K and Akt signaling pathways in the hippocampus and hypothalamus of Wistar rats treated with highly palatable food. AB - BACKGROUND/OBJECTIVES: Highly palatable food (HPF), which is enriched in simple sugars and saturated fat, contributes to obesity and insulin resistance in humans. These metabolic changes are associated with serious complications of the central nervous system, including an elevated risk of cognitive dysfunction. We, herein, treated rats with HPF and then examined the insulin-signaling pathway, in particular, the levels of phosphatidylinositol-3 kinase (PI3K), Akt, and insulin receptor substrate-1 (IRS-1) in the hippocampus and hypothalamus. METHODS: Adult Wistar rats fed with HPF (heated or not during preparation) for 4 months and then measured the levels of PI3K, Akt, and IRS-1 in the hippocampus and hypothalamus, by western blotting and quantitative real-time polymerase chain reaction. RESULTS: We observed changes in body weight, glucose intolerance, and lipidemia, confirming that peripheral metabolic alterations were induced using this model. Hippocampal PI3K and hypothalamic Akt were affected in rats that are submitted to chronic exposure to an HPF diet. Moreover, heated HPF caused differentiated alterations in the regulatory subunit of PI3K in the hippocampus. DISCUSSION: Our data suggest that this diet alters insulin signaling differentially in each brain region, and that hippocampal changes induced by this diet could contribute to the understanding of cognitive impairments that are dependent on the hippocampus. PMID- 22305649 TI - Depletion of intracellular zinc induced apoptosis in cultured hippocampal neurons through Raf/MEK/ERK pathways. AB - An experiment was performed to observe the changes in Raf-1 kinase/mitogen activated protein kinase ERK (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways in cultured hippocampal neurons and its correlation with neurons apoptosis induced by intracellular zinc depletion. Cultured hippocampal neurons were exposed to a cell membrane-permeant zinc chelator TPEN (2 uM), and to TPEN plus zinc sulfate (5 uM) for 24 h. Cultures were then processed to detect neuronal viability by the methyl thiazolyl tetrazolium assay, while apoptosis rate was simultaneously observed by the flow cytometric analysis. Caspase-3, Raf 1, pMEK, pERK1/2, and pCREB protein levels were examined by Western blot assays. The viability in TPEN-incubated neurons was notably decreased, apoptosis rate and expression of caspase-3 significantly increased compared to untreated controls. The significant down-regulation of Raf/MEK/ERK signaling pathway and expression of pCREB were decreased in TPEN-treated neurons. Co-addition of zinc almost completely reversed TPEN-induced alterations described. The results demonstrated zinc-modulated apoptosis and the expression of Raf/MEK/ERK at the protein level in hippocampal neurons. It is possible that zinc depletion-induced apoptosis in cultured hippocampal neurons may be relevant to the changes of Raf/MEK/ERK signaling pathway. PMID- 22305650 TI - Association between poor nutritional status and severe depression in Korean cerebral infarction patients. AB - OBJECTIVE: The purpose of this study was to assess the association between cerebral infarction (CI), nutritional status, and depression. METHODS: Subjects with and without CI (n = 146; 73 CI vs. 73 non-CI) were recruited from Kyung Hee University Medical Center (Seoul, Korea) and were matched according to age and gender. The subjects' medical histories, health-related behavioral habits, food intake, nutritional assessment, and depression status were analyzed. RESULTS: The prevalence of hypertension or diabetes were much higher in subjects in the CI group than in the non-CI group (P < 0.001). Subjects with CI registered lower dietary intakes of potassium, dietary fiber, fish, fruits, and vegetables than non-CI subjects (P < 0.05). By the mini-nutritional assessment (MNA) classification, malnutrition affected 57.5% of subjects in the CI group, but none of the subjects in the non-CI group (P < 0.001). The average Beck depression inventory (BDI) score was 43.6 +/- 7.7 points in the CI group and 20.6 +/- 13.1 points in the non-CI group (P < 0.001). Higher MNA scores (well-nourished status) were inversely associated with CI prevalence (odds ratio (OR) = 0.23; 95% CI: 0.07, 0.79) after controlling for age, gender, medical history, and health related factors, whereas BDI was not associated with CI prevalence (OR = 1.32; 95% CI: 0.90, 1.94). DISCUSSION: CI patients had several comorbidities, inappropriate health-related behavioral habits, malnourished status, and severe depression prior to CI onset. Indices of well-nourished status were inversely associated with CI. Accordingly, it would be desirable to develop a protocol for medical nutrition therapy in CI patients to improve nutritional status. PMID- 22305651 TI - Malnutrition during central nervous system growth and development impairs permanently the subcortical auditory pathway. AB - The brain that grows and develops under the continued influence of malnutrition presents permanent impairment on functioning and neurotransmitter release. The aim of this study was to investigate the chronic effects of neonatal food restriction on neurochemical and neurodynamical aspects within the primary auditory sensory pathway. Our working hypothesis is that neonatal malnutrition may affect the flow of primary sensory information both at a neurochemical and neurodynamical level. To test this hypothesis, three groups of rats were assigned, from birth to 370 days of life, to the following dietary scheme: a well-nourished (WN) group fed ad libitum lab chow diet; an undernourished (UN) group fed 60% of diet consumed by WN group; and a rehabilitated group, undergoing same dietary restriction as undernourished until 42 days of age and thereafter fed ad libitum until the end of the experiment. At 370 days of age, the animals were submitted to brainstem auditory-evoked potentials (BAEPs) recordings and sacrificed for neurochemical evaluation of glutamate release. Undernutrition decreased glutamate release in the cortex, hippocampus, midbrain and brainstem, and significantly increased the latency of BAEP wave V. In addition; the re establishment of the dietary conditions was not sufficient to reverse the neurochemical and electrophysiological alterations observed in the UN group. Taken altogether, our results suggest that malnutrition imposed at a critical development period caused an irreversible effect within the auditory primary sensory pathway. PMID- 22305652 TI - Dietary supplementation with decaffeinated green coffee improves diet-induced insulin resistance and brain energy metabolism in mice. AB - OBJECTIVES: There is accumulating evidence that coffee consumption may reduce risk for type 2 diabetes, a known risk factor for Alzheimer's and other neurological diseases. Coffee consumption is also associated with reduced risk for Alzheimer's disease and non-Alzheimer's dementias. However, preventive and therapeutic development of coffee is complicated by the cardiovascular side effects of caffeine intake. As coffee is also a rich source of chlorogenic acids and many bioactive compounds other than caffeine, we hypothesized that decaffeinated coffee drinks may exert beneficial effects on the brain. METHODS: We have investigated whether dietary supplementation with a standardized decaffeinated green coffee preparation, Svetol(r), might modulate diet-induced insulin resistance and brain energy metabolism dysfunction in a high-fat diet mouse model. RESULTS: As expected, dietary supplementation with Svetol(r) significantly attenuated the development of high-fat diet-induced deficits in glucose-tolerance response. We have also found that Svetol(r)) treatment improved brain mitochondrial energy metabolism as determined by oxygen consumption rate. Consistent with this evidence, follow-up gene expression profiling with Agilent whole-genome microarray revealed that the decaffeinated coffee treatment modulated a number of genes in the brain that are implicated in cellular energy metabolism. DISCUSSION: Our evidence is the first demonstration that dietary supplementation with a decaffeinated green coffee preparation may beneficially influence the brain, in particular promoting brain energy metabolic processes. PMID- 22305653 TI - Index finger position fluctuations reflect multi-muscle coordination. AB - We hypothesized that movement fluctuations in the index finger reflect the integrated result of the coordination of multiple muscles because index finger movements are determined by the cooperation of multiple muscles spanning the metacarpophalangeal (MCP) joint. To evaluate this hypothesis, the aim of the present study was to examine the fluctuations of the index finger in abduction adduction and extension-flexion directions during a position-holding task using two laser displacement sensors. Eleven healthy men maintained their index finger position while supporting a load at 5% of the maximal voluntary contraction force. To maintain the position of the index finger, displacement of the index finger in the abduction-adduction and extension-flexion directions was measured from a distance with two laser displacement sensors that were positioned to the lateral side of and above the index finger. The index finger movements fluctuated around the target position in not only the abduction-adduction direction but also the extension-flexion direction. The path length of finger displacement and the standard deviation of finger acceleration were significantly greater in the extension-flexion direction than in the abduction-adduction direction. These results suggest that the index finger movements quantified by two laser displacement sensors reflect the coordination of multiple muscles spanning the MCP joint. PMID- 22305654 TI - Heritable genome-wide variation of gene expression and promoter methylation between wild and domesticated chickens. AB - BACKGROUND: Variations in gene expression, mediated by epigenetic mechanisms, may cause broad phenotypic effects in animals. However, it has been debated to what extent expression variation and epigenetic modifications, such as patterns of DNA methylation, are transferred across generations, and therefore it is uncertain what role epigenetic variation may play in adaptation. RESULTS: In Red Junglefowl, ancestor of domestic chickens, gene expression and methylation profiles in thalamus/hypothalamus differed substantially from that of a domesticated egg laying breed. Expression as well as methylation differences were largely maintained in the offspring, demonstrating reliable inheritance of epigenetic variation. Some of the inherited methylation differences were tissue specific, and the differential methylation at specific loci were little changed after eight generations of intercrossing between Red Junglefowl and domesticated laying hens. There was an over-representation of differentially expressed and methylated genes in selective sweep regions associated with chicken domestication. CONCLUSIONS: Our results show that epigenetic variation is inherited in chickens, and we suggest that selection of favourable epigenomes, either by selection of genotypes affecting epigenetic states, or by selection of methylation states which are inherited independently of sequence differences, may have been an important aspect of chicken domestication. PMID- 22305655 TI - Fatal infection in two Icelandic stallions caused by Halicephalobus gingivalis (Nematoda: Rhabditida). AB - Opportunistic infections with the free living nematode Halicephalobus gingivalis are infrequently reported in horses but the cases are widespread geographically. The nematodes are believed to penetrate wounds and subsequently reproduce within the host tissues. This paper reports two cases of a fatal disease in stallions of the Icelandic breed in Iceland. Case 1: a stallion, which sustained injuries to the mouth after an accident, developed severe neurological signs and had to be euthanatized. Histological examination revealed mild inflammation and malacia in the cerebellum associated with the presence of numerous H. gingivalis nematodes. Case 2: a stallion that started swerving to one side and lost balance was euthanatized due to lack of response to therapy and rapid deterioration. Histological examination revealed numerous H. gingivalis nematodes in the cerebellum, brain stem, cervical spinal cord and in the meninges, with minimal reactive changes. In case 1 the infection presumably was acquired by nematodes from soil penetrating through wounds in the mouth. The mode of the H. gingivalis infection in case 2 is uncertain. These are the first cases of H. gingivalis infection reported from Iceland and the second report from the Nordic countries. PMID- 22305656 TI - Point mutations in the Theileria annulata cytochrome b gene is associated with buparvaquone treatment failure. AB - Theileriosis is an economically important haemoprotozoal disease with high morbidity and mortality in cattle. Buparvaquone is very effective in the treatment of Theileria infections in cattle. The present study reported an outbreak of bovine tropical theileriosis in Fars Province, southern Iran with buparvaquone treatment failure associated with mutations in drug-binding sites of its causative agent. The infected animals (n=8) exhibited poor condition, fever, anemia, rough coat and superficial lymph node enlargement. Both blood smears and lymph nodes punctures were positive and further molecular examination revealed that these animals were infected with Theileria annulata. Death occurred in seven of the eight infected animals in spite of the buparvaquone treatment. At molecular study, two types of important single-base mutations were observed in the cytochrome b gene of the parasite. These changes resulted in amino acid mutations in the parasite cytochrome b from serine (AGT) 109 to glycine (GGT) for the six dead cases and proline (CCT) 233 to serine (TCT) for one dead case within strongly Q(o) drug-binding sites. In contrast, neither of these mutations was found in the parasite cytochrome b for the buvarvaquone-treated animal. It seems that these mutation sites are associated with resistance to buparvaquone, a hydroxynaphthoquinone compound. PMID- 22305657 TI - Trichinella spiralis infection induces beta-actin co-localized with thymosin beta4. AB - Trichinella spiralis (T. spiralis) infection in muscle is characterized by the vascular network for the nurse cell-larva complex. We showed in a previous report that thymosin beta4 was up-regulated during nurse cell formation by T. spiralis. As thymosin beta4 (Tbeta4) is the actin-sequestering protein that regulates actin polymerization, the expression pattern of beta-actin during the nurse cell formation was analyzed. The protein level of beta-actin in muscle fibers 10 days after infection was significantly increased, and its expression remained high in the nurse cells for six weeks. In order to investigate the functional relationship between Tbeta4 and beta-actin, localization of two proteins was analyzed. Immunofluorescence showed that Tbeta4 and beta-actin were co-localized in the T. spiralis-infected nurse cells from 10 days to six weeks. The expression patterns of other actin-binding proteins, including thymosin beta10 (Tbeta10), subunits of the Arp2/3 complex, subunits of Capping protein, profilin, and cofilin, were also analyzed at the mRNA level. Tbeta10 expression was also increased during nurse cell formation. Expressions of the Arp2/3 complex was increased at 21 days after infection and Capping proteins was increased during nurse cell formation but shows different expression patterns, depending on the subunit. Profilin and cofilin were specifically increased in the muscle fibers from 14 days after infection. These data show that Tbeta4 and beta-actin are over expressed during nurse cell formation upon T. spiralis infection and may be involved in nurse cell formation along with other actin-binding proteins. PMID- 22305658 TI - Prevalence and trends of benzodiazepine use among Veterans Affairs patients with posttraumatic stress disorder, 2003-2010. AB - BACKGROUND: Although the Veterans Affairs and Department of Defense (VA/DoD) clinical guidelines for management of posttraumatic stress disorder (PTSD) recommend against routine benzodiazepine use, little is known about the trends and clinical and prescription profiles of benzodiazepine use since these guidelines were released in 2004. METHODS: This retrospective study included 64,872 patients with a PTSD diagnosis received from care at facilities in VA Northwest Veterans Integrated Service Network (VISN 20) during 2003-2010. Annual prevalence of any use was defined as any prescription for benzodiazepines, and long-term use was defined as >90 days' supply, in a year. Gender-specific logistic regressions were fit to estimate any and long-term benzodiazepine use, test for linear trends over 8-years and explore factors associated with trends. RESULTS: The trend of age-adjusted benzodiazepine use over 8-years rose significantly from 25.0 to 26.8% among men and 31.2 to 38.8% among women. Long term use in men and women increased from 15.4 to 16.4% and 18.0 to 22.7%, respectively. Comorbid psychiatric and alcohol use disorders (AUD) were associated with a greater increase in long-term use of benzodiazepines. In 2010, 61% of benzodiazepine users received >90 days' supply. Among those prescribed benzodiazepines long-term, 11% had AUD and 47% were also prescribed opioids long term. CONCLUSION: Despite VA/DoD clinical guidelines recommending against routine use of benzodiazepines for PTSD, the adjusted prevalence of long-term use increased among men and women with PTSD in VISN 20. Widespread concomitant use of benzodiazepines and opioids suggests risk management systems and research on the efficacy and safety of these medications are needed. PMID- 22305659 TI - Electrochemical treatment of spent solution after EDTA-based soil washing. AB - The use of EDTA in soil washing technologies to remediate soils contaminated with toxic metals is prohibitive because of the large volumes of waste washing solution generated, which must be treated before disposal. Degradation of EDTA in the waste solution and the removal of Pb, Zn and Cd were investigated using electrochemical advanced oxidation processes (EAOP) with a boron-doped diamond anode (BDDA), graphite and iron anodes and a stainless-steel cathode. In addition to EAOP, the efficiency of electro-Fenton reactions, induced by the addition of H(2)O(2) and the regulation of electrochemical systems to pH 3, was also investigated. Soil extraction with 15 mmol kg(-1) of soil EDTA yielded waste washing solution with 566 +/- 1, 152 +/- 1 and 5.5 +/- 0.1 mg L(-1) of Pb, Zn and Cd, respectively. Treatments of the waste solution in pH unregulated electrochemical systems with a BDDA and graphite anode (current density 67 mA cm( 2)) were the most efficient and removed up to 98 +/- 1, 96 +/- 1, 99 +/- 1% of Pb, Zn and Cd, respectively, by electrodeposition on the cathode and oxidatively degraded up to 99 +/- 1% of chelant. In the electrochemical system with an Fe anode operated at pH 3, the chelant remained preserved in the treated solution, while metals were removed by electrodeposition. This separation opens up the possibility of a new EDTA recycling method from waste soil washing solution. PMID- 22305660 TI - Detection of Cryptosporidium in miniaturised fluidic devices. AB - Contamination of drinking water with the protozoan pathogen, Cryptosporidium, represents a serious risk to human health due to the low infectious dose and the resistance of this parasite to chlorine disinfection. Therefore, several countries have legislated for the frequent monitoring of drinking water for Cryptosporidium presence. Existing approved monitoring protocols are however time consuming and do not provide essential information on the species, virulence or viability of detected oocysts. Rapid, more information-rich and automatable systems for Cryptosporidium detection are highly sought-after, and numerous miniaturised devices have been developed to address this need. This review article aims to summarise the state-of-the-art and compare the performance of these systems in terms of detection limit, ability to determine species, viability and performance in the presence of interferents. Finally, conclusions are drawn with regard to the most promising methods and directions of future research. PMID- 22305661 TI - National animal health surveillance: Return on investment. AB - A weighted benefit-cost analysis (BCA) supports prioritization of animal health surveillance activities to safeguard animal agriculture industries and reduce the impact of disease on the national economy. We propose to determine the value of investment in surveillance by assessing benefits from: avoiding disease incursion and expansion modified by the probability of occurrence of the disease event, the sensitivity of systems to detect it, and the degree to which we can mitigate disease impact when detected. The weighted benefit-cost ratio is the modified value of surveillance as laid out above divided by the cost of surveillance. We propose flexible, stream-based surveillance that capitalizes on combining multiple streams of information from both specific pathogen based and non pathogen based surveillance. This stream-based type of system provides high value with lower costs and will provide a high return for the funds invested in animal health surveillance. PMID- 22305662 TI - Research ethics board approval for an international thromboprophylaxis trial. AB - BACKGROUND: Research ethics board (REB) review of scientific protocols is essential, ensuring participants' dignity, safety, and rights. The objectives of this study were to examine the time from submission to approval, to analyze predictors of approval time, and to describe the scope of conditions from REBs evaluating an international thromboprophylaxis trial. METHODS: We generated survey items through literature review and investigators' discussions, creating 4 domains: respondent and institutional demographics, the REB application process, and alternate consent models. We conducted a document analysis that involved duplicate assessment of themes from REB critique of the protocol and informed consent forms (ICF). RESULTS: Approval was granted from 65 REB institutions, requiring 58 unique applications. We analyzed 44 (75.9%) of 58 documents and surveys. Survey respondents completing the applications had 8 (5-12) years of experience; 77% completed 4 or more REB applications in previous 5 years. Critical care personnel were represented on 54% of REBs. The time to approval was a median (interquartile range) of 75 (42, 150) days, taking longer for sites with national research consortium membership (89.1 vs 31.0 days, P = .03). Document analysis of the application process and ICF yielded 5 themes: methodology, data management, consent procedures, cataloguing, and miscellaneous. Protocol-specific themes focused on trial implementation, external critiques, and budget. The only theme specific to the ICF was risks and benefits. The most frequent comments on the protocol and ICF were about methodology and miscellaneous issues; ICF comments also addressed study risks and benefits. CONCLUSIONS: More studies on methods to enhance efficiency and consistency of the REB approval processes for clinical trials are needed while still maintaining high ethical standards. PMID- 22305663 TI - [Analysis of the results of the 2010 External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology]. AB - The External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology includes controls for bacteriology, serology, mycology, parasitology, mycobacteria, virology and molecular microbiology. This article presents the most important conclusions and lessons of the 2010 controls. As a whole, the results obtained in 2010 confirm the excellent skill and good technical standards found in previous years. However, erroneous results can be obtained in any laboratory and in clinically relevant determinations. The results of this program highlight the need to implement both internal and external controls to ensure maximal quality of microbiological tests(1). PMID- 22305664 TI - [Analysis of the results of the 2010 External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology for HIV-1, HCV, and HBV viral loads]. AB - Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most important markers for the follow-up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of the results obtained by microbiology laboratories. This article summarized the results obtained in the 2010 External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology for HIV-1, HCV, and HBV viral loads and HCV genotyping. In the HIV-1 program, a total of five standards were sent. One standard consisted of seronegative human plasma, while the remaining four contained plasma from three different viremic patients, in the range of 3-5 log(10) copies/mL; two of these standards were identical, with the aim of determining repeatability. A significant proportion of the laboratories (22.6% on average) obtained values out of the accepted range (mean +/- 0.2 log(10)copies/mL), depending on the standard and on the method used for quantification. Repeatability was very good, with up to 95% of laboratories reporting results within the limits (Delta<0.5 log(10)copies/mL). The HBV and HCV program consisted of two standards with different viral load contents. Most of the participants, 86.1% in the case of HCV and 87.1% in HBV, obtained all the results within the accepted range (mean +/- 1.96 SD log(10)UI/mL). Post-analytical errors due to mistranscription of the results were detected in these controls. Data from this analysis reinforce the utility of proficiency programs to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase in overall quality. Due to interlaboratory variability, use of the same method and the same laboratory for patient follow-up is advisable. PMID- 22305665 TI - [Diagnosis of congenital infection]. AB - In general, congenital diagnosis is based on: a) maternal serologic assays; b) microbiologic study of amniotic fluid or fetal blood sampling; and c) serology in children and microorganism detection by polymerase chain reaction (PCR) or culture. Congenital infections due to cytomegalovirus, herpes simplex, varicella, B19 erythrovirus and toxoplasmosis are usually the result of primary infection in the mother. Therefore, when IgG antibodies are detected before pregnancy, these infections are ruled out. Definitive serologic diagnosis of acute infection in pregnant women requires the demonstration of seroconversion (i.e., from seronegative to seropositive). In these cases, amniotic fluid or fetal blood sampling should be performed to determine the presence of intrauterine congenital infection. Cytomegalovirus, rubella and toxoplasmosis can be diagnosed by detection of specific IgM antibodies in fetal blood. However, PCR in amniotic fluid has replaced conventional prenatal diagnostic techniques, including fetal blood sampling, in the diagnosis of these infections. In the newborn, these infections may be confirmed by measuring IgM specific antibodies. B19 erythrovirus can be detected by PCR in amniotic fluid or fetal blood. Congenital varicella-zoster infection may be diagnosed on the basis of persistence of IgG antibodies after birth. Definitive diagnosis of herpes simplex virus infection requires viral isolation. Swabs or scraping from clinical specimens can be inoculated into susceptible cell lines for isolation. PMID- 22305666 TI - [West Nile virus infection]. AB - West Nile virus (WNV) is an arbovirus usually transmitted by mosquitoes. The main reservoirs are birds, although the virus may infect several vertebrate species, such as horses and humans. Up to 80% of human infections are asymptomatic. The most frequent clinical presentation is febrile illness, and neuroinvasive disease can occur in less than 1% of cases. Spain is considered a high-risk area for the emergence of WNV due to its climate and the passage of migratory birds from Africa (where the virus is endemic). These birds nest surrounding wetlands where populations of possible vectors for the virus are abundant. Diagnosis of human neurological infections can be made by detection of IgM in serum and/or cerebrospinal fluid samples, demonstration of a four-fold increase in IgG antibodies between acute-phase and convalescent-phase serum samples, or by detection of viral genome by reverse transcription-polymerase chain reaction (especially useful in transplant recipients). Since WNV is a biosafety level 3 agent, techniques that involve cell culture are restricted to laboratories with this level of biosafety, such as reference laboratories. The National Program for the Surveillance of WNV Encephalitis allows the detection of virus circulation among birds and vectors in areas especially favorable for the virus, such as wetlands, and provides information for evaluation of the risk of disease in horses and humans. PMID- 22305667 TI - [Filariasis in clinical practice]. AB - Filariases are infections caused by distinct species of nematodes. These infections are transmitted through insect bites and primarily affect lymph nodes and skin. Filariases are classified as neglected diseases and affect millions, producing severe disability and social stigma. This type of infection is rarely diagnosed in travellers, as prolonged stays in endemic areas are usually required acquire infection. Infections may be asymptomatic, and clinical manifestations depend on the host immune response to the infection and the parasite burden. Diagnosis is based on the demonstration of microfilariae in blood or skin, but there are other methods that support the diagnosis. Individual treatment is effective, but community interventions, mostly mass drug administration, have helped to diminish the incidence of filariases. PMID- 22305668 TI - [Antifungal therapy update: new drugs and medical uses]. AB - Increases in the rates of fungal infections, as well as their associated morbidity and mortality has led to a need for additional antifungal agents. The most common serious fungal agents in immunosuppressed and critically ill patients are Candida spp. and Aspergillus spp., although other emerging fungi must be considered. Rational, early systemic antifungal treatment should be based on diagnostic imaging techniques and conventional mycological and non-culture-based procedures. While the availability of new therapeutic options is an important advance, antifungal therapy has become increasingly complex. In addition to the available antifungal armamentarium, recent research has resulted in the introduction of three new antifungal agents: micafungin, anidulafungin, and posaconazole. This article provides an update, based on the latest scientific evidence, of the clinical efficacy, pharmacokinetics, safety and dosing of antifungal drugs administered in the management of Candida spp., Aspergillus spp., Cryptococcus spp., Zygomycetes, Scedosporium spp. and Fusarium spp. PMID- 22305669 TI - [Methods for determination of HIV tropism and their clinical use]. AB - Determination of HIV-1 tropism is mandatory before using CCR5 antagonists in clinical practice. One drug of this class, maraviroc, has been approved for the treatment of HIV infection. The phenotypic assay, TrofileTM, was clinically validated in the clinical development program of maraviroc and has been widely used to select candidates for maraviroc therapy. Phenotypic tests, however, have the disadvantage of being complex, are costly and time-consuming, and their accessibility is limited, which hampers their routine use in clinical diagnosis. Genotypic assays, based on sequencing the third hypervariable (V3 loop) of the viral gene env, interpreted according to various genotypic bioinformatic tools, such as geno2pheno and PSSM, are faster and cheaper than phenotypic assays, and are also more accessible. In retrospective analyses of the maraviroc pivotal trials, genotypic methods using either conventional ("bulk") or deep-sequencing technology predicted virologic response to maraviroc similarly to phenotypic assays and are now included within several European recommendations to guide the clinical use of CCR5 antagonists. PMID- 22305670 TI - [Current options for predicting therapeutic response in chronically infected patients with hepatitis C virus genotype 1]. AB - Only about 50% of patients chronically infected with hepatitis C virus genotype 1 achieve a successful response to standard treatment with pegylated interferon alfa and ribavirin. Moreover, the recently approved protease inhibitors will have to be administered together with these drugs. Consequently, predicting response to standard treatment, ideally before starting it, remains an important challenge. Although several baseline predictors of treatment failure have been described, including clinical and virological factors, none of them is able to provide reliable predictions at the individual level. In addition, the development of multivariate models combining several predictive factors has not yet yielded predictions with the requisite reliability for use in clinical practice. Therefore, further research is needed to improve predictive models and to describe new factors that would enable us to predict treatment outcome with greater reliability and reproducibility. The development of candidate selection algorithms that help clinicians to identify which patients could benefit from the new therapies on the basis of their chances of responding to standard therapy is of major interest for both patient well-being and healthcare expense. This review attempts to provide a view of the current options for predicting the response to pegylated interferon-alfa plus ribavirin therapy in patients chronically infected with hepatitis C virus genotype 1. PMID- 22305671 TI - [Enterococcus: phenotype and genotype resistance and epidemiology in Spain]. AB - Enterococci are major nosocomial pathogens due to their intrinsic resistance to many antimicrobials as well as to their ability to acquire new mechanisms of resistance. Acquired resistance to beta-lactams is due to PBP5 overproduction or alterations in this protein. Beta-lactamase production is anecdotal. High-level resistance (HLR) to aminoglycosides is due to the production of aminoglycoside modifying enzymes that delete synergistic killing in association with cell wall active agents. The most frequent enzyme is AAC(6')- APH(2"), which inactivates all the aminoglycosides most frequently used in clinical practice. Acquired resistance to glycopeptides is due to the acquisition of gene clusters called vanA, vanB, vanD, vanE, vanG, vanL, vanM and vanN. Linezolid resistance is due to ribosomal mutations or to the acquisition of the cfr gene. Some isolates present diminished susceptibility to daptomycin. In Spain, both enterococcal resistance to beta-lactams and HLR to aminoglycosides are high. E. faecalis is almost uniformly susceptible to ampicillin. Enterococcal resistance to glycopeptides is low, with the exception of occasional outbreaks. The new antimicrobials (linezolid, daptomycin, tigecycline) are almost uniformly active against these microorganisms. Because of the wide dissemination of the high-risk clonal complexes CC2 and CC9 (E. faecalis), and CC17 (E. faecium), surveillance studies are required to detect antimicrobial resistance genes as well as to identify high risk clonal complexes in order to predict future trends in the acquisition of resistance genes. PMID- 22305672 TI - [Atypical mycobacteria and pulmonary involvement in infectious diseases]. AB - Nontuberculous mycobacteria (NTM) are increasingly associated with infectious pulmonary disease. NTM are ubiquitous environmental pathogens with high isolation rates worldwide. The greater frequency of NTM associated with pulmonary diseases is probably due to a combination of increased exposure, improved diagnostic methods and an increase in the prevalence of risk factors predisposing individuals to infection. Difficulty may arise in determining whether an isolate from a respiratory sample is in fact a contaminant or a pathogenic organism. The ATS/IDSA guidelines highlight the importance of following microbiological and clinical criteria in making a diagnosis of NTM lung infection. These criteria may not be useful for all NTM and species-level identification is strongly recommended. Mycobacteria identification by conventional methods has been the standard in most clinical microbiology laboratories. However, conventional testing alone does not allow identification of many NTM. Newer, rapid molecular methods such as commercially available nucleic acid probes, genomic amplification and DNA sequence analysis should be used. Communication between the clinician and the laboratorian is essential to decide whether an isolate could be sent to a reference laboratory to determine the best method for species identification. Although the CLSI has recently published an approved standard for NTM susceptibility testing, there is ongoing debate about the role of in vitro susceptibility for managing patients with NTM disease. The goal of this review is to describe the mycobacteria involved in lung disease, the factors that predispose to this infection, its diagnosis with alternative procedures and the correlation between in vitro and in vivo treatment response. PMID- 22305673 TI - [Implementation of quality standard UNE-EN ISO/IEC 17043 in the External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology]. AB - The quality standard "UNE-EN-ISO 17043: 2010. Conformity assessment. General requirements for proficiency testing" applies to centers that organize intercomparisons in all areas. In the case of clinical microbiology laboratories, these intercomparisons must meet the management and technical standards required to achieve maximum quality in the performance of microbiological analysis and the preparation of test items (sample, product, data or other information used in the proficiency test) to enable them to be accredited. Once accredited, these laboratories can operate as a tool for quality control laboratories and competency assessment. In Spain, accreditation is granted by the Spanish Accreditation Body [Entidad Nacional de Acreditacion (ENAC)]. The objective of this review is to explain how to apply the requirements of the standard to laboratories providing intercomparisons in the field of clinical microbiology (the organization responsible for all the tasks related to the development and operation of a proficiency testing program). This requires defining the scope and specifying the technical requirements (personnel management, control of equipment, facilities and environment, the design of the proficiency testing and data analysis for performance evaluation, communication with participants and confidentiality) and management requirements (document control, purchasing control, monitoring of complaints / claims, non-compliance, internal audits and management reviews). PMID- 22305674 TI - Detection of uncharged or feebly charged small molecules by field-effect transistor biosensors. AB - This paper describes a new technique for the detection of uncharged or feebly charged small molecules (<400Da) using Si field-effect transistor (FET) biosensors that are signal-enhanced by gold nanoparticle (NP) charges under dry measurement conditions. NP charges are quickly induced by a chemical deposition (that is, Au deposition) and the indirect competitive immunogold assay, and strongly enhance the electrical signals of the FET biosensors. For the validation of signal enhancement of FET biosensors based on NP charges and detection of uncharged or feebly charged small molecules, mycotoxins (MTXs) of aflatoxin-B1 (AFB1), zearalenone (ZEN), and ochratoxin-A (OTA) were used as target molecules. According to our experimental results, the signal is 100 times more enhanced than the use of the existing solution FET biosensing techniques. Furthermore, this method enables the FET biosensor to quantitatively detect target molecules, regardless of the ionic strengths, isoelectric points (pI), or pHs of the measured sample solutions. PMID- 22305675 TI - Rare presentation of unicentric Castleman's disease in the parotid gland. AB - Castleman's disease is a rare benign lymphoproliferative disorder of unknown etiology; however, recent data have suggested a strong association with human herpesvirus type 8 and hypersecretion of the cytokine interleukin 6. Castleman's disease can present anywhere throughout the body; however, it is most commonly detected in the chest, neck, or abdomen. Two main forms of the disease have been identified according to location: unicentric and multicentric. Unicentric Castleman's disease differs from the multicentric form in that patients are often asymptomatic, and surgical resection of the lesion is considered curative. This unicentric or multicentric nature often serves as a distinguishing feature between benign or potentially malignant presentations. The diagnosis of Castleman's disease is challenging because of its nonspecific manifestation. The most reliable diagnosis is achieved though surgical resection and histopathologic confirmation. We report a rare case of unicentric Castleman's disease in the parotid gland and emphasize its importance in the differential diagnosis of oral facial masses. PMID- 22305676 TI - First record of Plesiadapiformes (Primates, Mammalia) from Spain. PMID- 22305677 TI - Comparing ion conductance recordings of synthetic lipid bilayers with cell membranes containing TRP channels. AB - In this article we compare electrical conductance events from single channel recordings of three TRP channel proteins (TRPA1, TRPM2 and TRPM8) expressed in human embryonic kidney cells with channel events recorded on synthetic lipid membranes close to melting transitions. Ion channels from the TRP family are involved in a variety of sensory processes including thermo- and mechano reception. Synthetic lipid membranes close to phase transitions display channel like events that respond to stimuli related to changes in intensive thermodynamic variables such as pressure and temperature. TRP channel activity is characterized by typical patterns of current events dependent on the type of protein expressed. Synthetic lipid bilayers show a wide spectrum of electrical phenomena that are considered typical for the activity of protein ion channels. We find unitary currents, burst behavior, flickering, multistep-conductances, and spikes behavior in both preparations. Moreover, we report conductances and lifetimes for lipid channels as described for protein channels. Non-linear and asymmetric current voltage relationships are seen in both systems. Without further knowledge of the recording conditions, no easy decision can be made whether short current traces originate from a channel protein or from a pure lipid membrane. PMID- 22305678 TI - Pneumococcal polysaccharide vaccine at 12 months of age produces functional immune responses. AB - BACKGROUND: Infections with Streptococcus pneumoniae (pneumococcus) are a cause of significant child mortality. Pneumococcal glycoconjugate vaccines are expensive and provide limited serotype coverage. The 23-valent pneumococcal polysaccharide vaccine (Pneumovax) might provide wider serotype coverage but is reported to be weakly immunogenic in children less than 2 years of age. We have previously reported that Pneumovax administered to healthy 12-month-old Fijian infants elicits significant serotype-specific IgG responses. However, the functional capacity of these responses in 12-month-old infants is not known. OBJECTIVE: We sought to assess the functional, serotype-specific immune response of 12-month-old infants after immunization with Pneumovax. METHODS: Functional responses of 12-month-old infants were assessed by using the opsonophagocytic and antibody avidity assay against 8 serotypes and 23 serotypes, respectively. RESULTS: Seventy-one percent of infants produced strong opsonophagocytic activity against 4 of 8 serotypes, and 30% produced high-avidity serotype-specific IgG antibodies to 10 of 23 serotypes at 2 weeks after Pneumovax. Responses were protective for most serotypes that cause disease in Western countries, whereas responses to most of the epidemiologically relevant serotypes for developing countries were low. CONCLUSION: This is the first comprehensive study evaluating the functional antibody response to Pneumovax in 12-month-old infants. Pneumovax induced functional antibody responses to several serotypes causing disease in Western countries but induced poorer responses to serotypes that are responsible for the majority of disease in developing countries. Pneumovax might be of benefit in some populations, but further studies are required before this can be recommended in developing countries. PMID- 22305679 TI - Prevalence of eczema and food allergy is associated with latitude in Australia. PMID- 22305680 TI - Advances in upper airway diseases and allergen immunotherapy in 2011. AB - The purpose of this review is to highlight recently published important articles on upper airway diseases and allergen immunotherapy. We review articles on rhinitis, sinusitis, conjunctivitis, and immunotherapy. New insights into epidemiology, pathophysiology, diagnosis, and therapy are described for each of the above diseases. PMID- 22305681 TI - IgE against bed bug (Cimex lectularius) allergens is common among adults bitten by bed bugs. PMID- 22305682 TI - Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma: relationship to disease severity. AB - BACKGROUND: Matrix metalloproteinase (MMP)-12 has been implicated in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and asthma. The influence of disease severity on sputum MMP-12 concentrations and activity is not known. OBJECTIVES: We sought to examine the relationship between disease severity assessed by means of lung function and computed tomography (CT) and induced sputum MMP-12 concentrations and activity in patients with asthma and COPD. METHODS: In 208 subjects (109 asthmatic patients, smokers and never smokers, mild, moderate, and severe; 53 patients with COPD, smokers and exsmokers, mild, moderate, and severe; and 46 healthy control subjects, smokers and never smokers), we measured induced sputum MMP-12 concentrations (ELISA) and enzyme activity (fluorescence resonance energy transfer), sputum cell MMP12 mRNA expression (quantitative PCR [qPCR]), diffusing capacity for carbon monoxide (Dlco), and CT assessment of emphysema (percentage of low-attenuation areas at less -950 Hounsfield units). RESULTS: Sputum MMP-12 concentrations are greater in patients with COPD and smokers with asthma than in healthy nonsmokers (P = .003 and P = .035, respectively) but similar to those seen in healthy smokers. In patients with COPD, disease severity, when measured by means of CT-assessed emphysema, but not by means of spirometry or Dlco values, is directly associated with sputum MMP-12 concentrations and activity. In the asthma groups there is no significant association between disease severity and sputum MMP-12 concentrations or activity. CONCLUSIONS: Sputum MMP-12 concentrations and activity in patients with COPD are directly associated with the extent of emphysema measured by means of CT. This finding supports a role for MMP-12 in the pathogenesis of COPD and might suggest that blocking MMP-12 activity in patients with COPD could prevent the further development of emphysema. PMID- 22305683 TI - Limiting inflammatory response to cardiopulmonary bypass: pharmaceutical strategies. AB - A significant inflammatory response and subsequent organ dysfunction is known to be associated with the use of CPB. Pharmaceutical interventions, such as corticosteroids, statins and ACE-Is can attenuate the post-CPB inflammatory and immune response, by so doing, either directly or indirectly, reduce incidence of postoperative complications. Apart from its effects on lipids, statins have been found to reduce postoperative oxidative stress that may partly contribute towards improved graft patency. In addition, certain ACE-inhibitors can promote a pro fibrinolytic environment, whose role on maintaining graft patency and clinical outcomes warrant further investigation. There is increasing evidence to support the use of combined clopidogrel with aspirin following CABG to improve graft patency, although its impact on reducing postoperative adverse events remains unclear. Factors such as drug bioavailability and individual variability in drug responses and metabolism of these antiplatelet agents can significantly influence clinical outcomes. PMID- 22305684 TI - Surgically relevant aortic arch mapping using computed tomography. AB - BACKGROUND: Recent advances in surgical repair of aortic arch pathologies have increasingly used endovascular stent-graft technology. The purpose of this study was to map the aortic arch diameters, branch orientations, and center line distances using a commercially available three-dimensional computed tomography based software package and to propose a prototype design. METHODS: TeraRecon 3D imaging software was used for morphological assessment of computed tomography scans from 45 patients (mean age: 68 years; 26 males, 19 females). In each patient, 13 measurements were made in relation to the center line, including diameters at several preset points, distances, and branch vessel orientations. RESULTS: The mode of the proximal diameters (2 cm and 4 cm distal to coronary artery) was 32 mm and 34 mm. The mode of the distance between the innominate and left common carotid arteries was 5 mm and 6 mm, and the mode of the distance between the left common carotid artery and left subclavian artery was 8 mm. Most commonly, the left common carotid artery was anterior to the other arch branches by 3 to 5 mm. CONCLUSIONS: These anatomic measurements provide useful information for the advancement of minimally invasive and safer surgical repair of the aortic arch. Based on the most commonly observed measurements, a standardized off-the shelf stent-graft is proposed that would be appropriate for the majority of patients. PMID- 22305685 TI - Randomized trials in angioplasty and stenting of the renal artery: tabular review of the literature and critical analysis of their results. AB - As the incidence of hypertension (HTN) continues to rise, finding the optimal treatment of this multifactorial disease is critical. Renal artery stenosis (RAS) is a known etiology for HTN and is associated with declining renal function. Other than medications, the original gold standard for treatment of HTN from RAS was with an open surgical revascularization or nephrectomy. Since then, endovascular interventions for RAS have been reported to be technically possible, but their efficacy over medications or surgery has yielded conflicting results in case series and randomized trials. This tabular review summarizes the results of randomized trials that compared the outcomes of endovascular renal artery interventions with nonendovascular techniques (including medical and surgical treatments) for the treatment of HTN and renal dysfunction. Based on these data, the strengths and weaknesses of individual trials are critically analyzed to better define the methods to identify and treat patients with RAS. PMID- 22305686 TI - Endoscopic endonasal multilayer repair of traumatic ethmoidal roof cerebrospinal fluid rhinorrhea in children. AB - OBJECTIVE: Pediatric traumatic cerebrospinal fluid (CSF) leak is a challenging problem in diagnosis and management. Posttraumatic leaks frequently present by intermittent rhinorrhea or by recurrent attacks of meningitis, which can be the only presenting symptom. The objective of this study is to present our experience in management of pediatric traumatic ethmoidal roof CSF leaks using a multilayer repair technique via an endoscopic approach. METHODS: Ten pediatric patients (aged 4-14 years, six males and four females) presenting with posttraumatic ethmoidal roof CSF rhinorrhea were operated upon between January 2007 and December 2010, using an endoscopic endonasal multilayer repair technique. Preoperative radiological evaluation included both multidetector computed tomography (MDCT) with ultra-thin 1mm cuts, and magnetic resonance imaging (MRI) high resolution coronal T2-weighted sequence. Intraoperatively, the GE InstaTrakTM 3500 electromagnetic navigation system was used in all cases. Postoperative follow-up was done clinically by regular endoscopic examinations and radiologically by MRI assessment using the same preoperative protocol. RESULTS: Clinically all patients presented with unilateral intermittent watery rhinorrhea with periods ranging from 5 to 24 months before operation. Seven cases had a history of recurrent meningitis. Defects were confined to ethmoidal roof in all 10 cases (right side in seven and left side in three), and ranged in size from 2 to 7 mm(2) (mean 3.9 +/- 1.5 mm(2)). Two cases had more than one defect on the same side. All defects were identified preoperatively using our radiological protocol. One case was associated with a meningocele with no brain herniation and another case was associated with a small meningoencephalocele. Mean postoperative hospitalization was 6 days (range 4-8 days). None of our patients developed any intra or postoperative complications or required revision surgery with a 100% success rate after a mean follow-up duration of 29.4 +/- 14.4 months (range 12-52 months). CONCLUSIONS: Pediatric posttraumatic CSF leaks involving the ethmoidal roof can be successfully managed via the endonasal endoscopic route using a multilayer repair technique, thus limiting complications associated with external approaches. Preoperative imaging including MDCT and high resolution MRI is of paramount importance for detecting the defect site and for planning surgery. PMID- 22305687 TI - Lipoteichoic acid from Staphylococcus aureus induced expression of MMP-9 in human middle ear epithelial cells. AB - OBJECTIVE: Change in matrix metalloproteinases (MMPs) and regulation of their tissue inhibitors of metalloproteinases (TIMPs) could play certain role in the pathogenesis of otitis media. This study was designed to evaluate the modulation of MMPs and TIMPs in middle ear epithelium by lipoteichoic acid (LTA) isolated from Staphylococcus aureus. METHODS: Human middle ear epithelial (HMEE) cells were treated with LTA. MMP activities were examined by PCR, ELISA and zymography, and levels of TIMPs were measured by PCR and ELISA. RESULTS: LTA isolated from S. aureus increased MMP-9 mRNA expression and secretion in HMEE cells, whereas no effect on the expressions of MMP-1, -2, -3, -7 and TIMP-1, -2 was observed. CONCLUSIONS: LTA increased the activity of MMP-9, not TIMPs in middle ear epithelia, suggesting that disturbed balance between MMP-9 and TIMPs could play an active role in LTA-induced otitis media. PMID- 22305688 TI - Probiotics and otitis media in children. AB - OBJECTIVE: An alternative option in the prophylaxis and the management of infectious diseases is the use of probiotics, which are known to stabilize gut microbiota and stimulate immune function. Otitis media (OM) is the most common bacterial infection in childhood. The aim of this review is to present the current knowledge of the effects of probiotics on OM. METHODS: A PUBMED search was made to review the relevant literature, and publications on probiotics and otitis media in children were included. Additional studies were obtained from the references of the selected articles. RESULTS: Only a few studies using different probiotic strains and study populations have investigated the effects of probiotics on OM. Five studies investigating the effects of oral probiotics, and three studies investigating the effect of probiotic nasal spray treatment were included in this review. Oral probiotics have reduced the incidence of OM in healthy children in one of two studies (days with OM: probiotic 0.5 vs. control 1.0; p=0.003) and in newborns in one of two studies (incidence of OM: probiotic 22%, placebo 50%; p=0.014), but has had no effect on OM in one study in otitis prone children. Nasal spray treatment containing alpha streptococci has led to clinical improvement in children with recurrent or secretory OM in two of three studies (cured: probiotic 42% vs. placebo 22%, p=0.02; recovery: probiotic 7/19 patients vs. placebo 1/17, p<0.05). CONCLUSIONS: Although there are some promising results, the lack of confirmative studies makes it difficult to draw any conclusions. More studies are needed to identify the most promising probiotic strains and study populations, and to evaluate the mechanisms behind the possible effects of probiotics on OM. PMID- 22305689 TI - Chronic rhinosinusitis in children--bacteriological analysis in terms of cytological examination. AB - INTRODUCTION: The mechanisms of inflammatory response occurring in chronic rhinosinusitis in children are multifactorial. Besides the history and a physical examination, amongst diagnostic tools there are cytological and bacteriological examinations. OBJECTIVES: 1 Determining the nature of the bacterial flora present in the nasal cavities and paranasal sinuses in children with chronic rhinosinusitis amongst patients of The Department of Paediatric Otolaryngology,Warsaw Medical University. 2 Determining the relation between bacterial strains and cytological examination of nasal mucosa in children with chronic rhinosinusitis. MATERIALS AND METHODS: The study group included 64 patients with chronic rhinosinusitis without polyps. The control group included 30 randomly chosen children. Diagnostic tests performed in both groups were: middle meatal culture and cytological examination from the inferior nasal concha and middle meatus. Statistical analysis was accomplished with Statistica 8.0. RESULTS: CONCLUSIONS: Damage to the respiratory epithelial surface is understood as damage to the innate immune barrier, and repeated antibiotic therapy with the subsequent repopulation of the epithelium accidentally by various bacteria can become responsible for the pathogenic effect of bacteria in chronic rhinosinusitis. PMID- 22305690 TI - Is quality good enough? PMID- 22305691 TI - The garden party. PMID- 22305692 TI - Evidence in diagnostic imaging: going beyond accuracy. PMID- 22305693 TI - Radiology advocacy group. PMID- 22305694 TI - Aspirin and angioplasty. PMID- 22305695 TI - ACR appropriateness criteria((r)) acute trauma to the knee. AB - There are more than 1 million visits to the ER annually in the United States for acute knee trauma. Many of these are twisting injuries in young patients who can walk and bear weight, and emergent radiography is not required. Several clinical decision rules have been devised that can considerably reduce the number of radiographic studies ordered without missing a clinically significant fracture. Although fractures are seen on only 5% of emergency department knee radiographs, 86% of knee fractures result from blunt trauma. In patients with falls or twisting injuries who have focal tenderness, effusion, or inability to bear weight, radiography should be the first imaging study performed. If radiography shows no fracture, MRI is best for evaluating for a suspected meniscal or ligament tear or patellar dislocation. Patients with knee dislocation should undergo radiography and MRI, as well as fluoroscopic angiography, CT angiography, or MR angiography. The ACR Appropriateness Criteria((r)) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. PMID- 22305696 TI - Impact of generational differences on the future of radiology: proceedings of the 11th annual ACR Forum. AB - The 2011 ACR Forum focused on the impact of generational differences on the future of radiology, seeking to inform ACR leadership and members on how best to address the influence of the new integrated workforce on the specialty of radiology and on individual practices. PMID- 22305697 TI - Quantitatively and qualitatively augmenting medical student knowledge of oncology and radiation oncology: an update on the impact of the oncology education initiative. AB - PURPOSE: The Oncology Education Initiative was established in 2007 in an effort to advance oncology and radiation oncology education at the undergraduate level. As a continuation of the initiative, the aim of this study was to determine whether these structured didactics would continue to increase overall medical student knowledge about oncologic topics. METHODS: Preclerkship and postclerkship tests examining concepts in general oncology, radiation oncology, breast cancer, and prostate cancer were administered. The 21-question, multiple-choice examination was administered at the beginning and end of the radiology clerkship, during which a 1.5-hour didactic session was given by an attending radiation oncologist. Changes in individual question responses, student responses, and overall categorical responses were analyzed. All hypothesis tests were two tailed with a significance level of .05. RESULTS: In the 2009-2010 academic year, 155 third-year and fourth-year students had average examination score improvements from 62% to 68.9% (P < .0001). Every topic (100%) showed improvement in scores, with the largest absolute improvement seen in the radiation oncology category, which increased from 56.5% to 71.8% (P < .0001). As the year proceeded, average examination scores increased among third-year students and decreased among fourth year students. CONCLUSIONS: In the successive years since its inception, the Oncology Education Initiative continues to show a significant improvement in medical students' knowledge of cancer. The initiative has also succeeded in providing radiation oncology education to all graduating medical students at the authors' institution. Dedicated oncology education in the undergraduate medical curriculum provides students with a better understanding of multidisciplinary oncology management. PMID- 22305698 TI - Practice analysis: a basis for content validity for american board of radiology examinations in diagnostic radiology. AB - The ABR performs practice analysis every 3 years, according to its strategic plan, in an effort to strengthen the content validity of its qualifying and certifying examinations as well as its maintenance of certification examinations. A nationwide survey of diagnostic radiologists was conducted in July 2010 for the purpose of determining the critically important and frequently performed activities in 12 clinical categories. The survey instrument was distributed electronically to 17,721 members of the ACR, with a unique identification code for each individual. A 5-point scale was established for both frequency and importance variables. The frequency scale ranged from 1 to 5 as follows: 1 = not applicable, 2 = occasionally, 3 = monthly, 4 = weekly, and 5 = daily. The scale for importance also ranged from 1 to 5: 1 = not applicable, 2 = not important, 3 = somewhat important, 4 = important, and 5 = essential. A total of 2,909 diagnostic radiologists (19.32%) participated. Of these, 2,233 (76.76%) indicated that they spent >=50% of their time in clinical practice. Because of its brevity of the list of the activities, results for the gastrointestinal category are presented in this article. The list of activities weighted according to importance and frequency is presented in this article and, as illustrated, could become the foundation for developing a more detailed blueprint for the gastrointestinal category certifying examinations in diagnostic radiology. Findings on demographic information are also presented. PMID- 22305699 TI - Adoption and meaningful use of computerized physician order entry with an integrated clinical decision support system for radiology: ten-year analysis in an urban teaching hospital. AB - PURPOSE: The aim of this study was to assess whether an integrated imaging computerized physician order entry (CPOE) system with embedded decision support for imaging can be accepted clinically. METHODS: The study was performed in a health care delivery network with an affiliated academic hospital. After pilot testing and user feedback, a Web-enabled CPOE system with embedded imaging decision support was phased into clinical use between 2000 and 2010 across outpatient, emergency department, and inpatient settings. The primary outcome measure was meaningful use, defined as the proportion of imaging studies performed with orders electronically created (EC) or electronically signed by an authorized provider. The secondary outcome measure was adoption, defined as the proportion of imaging studies that were ordered electronically, irrespective of who entered the order in the CPOE system. Univariate and multivariate regression analyses were performed to estimate trends and the significance of practice settings, examination modality, and body part to outcome measures. Chi-square statistics were used to assess differences across specialties. RESULTS: A total of 4.1 million imaging studies were performed during the study period. From 2000 to 2010, significant increases in meaningful use (for EC studies, from 0.4% to 61.9%; for electronically signed studies, from 0.4% to 92.2%; P < .005) and the adoption of CPOE (from 0.5% to 94.6%, P < .005) were observed. The use of EC studies was greatest in the emergency department and inpatient settings. Meaningful use varied across specialties; surgical subspecialties had the lowest rates of EC studies. CONCLUSIONS: Imaging CPOE with embedded decision support integrated into the IT infrastructure of the health care enterprise and clinicians' workflow can be broadly accepted clinically. PMID- 22305700 TI - Percutaneous needle vs surgical breast biopsy: previous allegations of overuse of surgery are in error. AB - PURPOSE: A recent paper in the American Journal of Surgery reported that surgery is used for 30% of breast biopsies, an excessive number. The investigators' stated biopsy volume included Current Procedural Terminology((r)) code 19125 ("excision of breast lesion identified by preoperative placement of radiological marker, open"). However, this code may often be used when a surgeon's primary intention is not biopsy but rather excision of a lesion. Therefore, the reported results may overstate the percentage of biopsies performed as surgical procedures. The aim of this study was to more accurately assess the use of percutaneous core needle biopsy (PNB) compared with surgical biopsy. METHODS: The nationwide Medicare Part B databases for 2004 to 2009 were used. Trends in use of codes 19100 (PNB without imaging), 19102 and 19103 (PNB with imaging), 19101 (open biopsy), and the aforementioned 19125 were determined. RESULTS: From 2004 to 2009, the volumes of PNB with imaging (codes 19102 and 19103) increased substantially, while the volume of code 19125 decreased substantially. If one includes all 19125 claims as biopsies, the 2009 frequency of surgical biopsies was 18%. If one considers all 19125 claims as excisions, the frequency of surgical biopsies was 2%. CONCLUSIONS: The previously published statement in the American Journal of Surgery that 30% of breast biopsies are done surgically is erroneous. Medicare data indicate that the true surgical breast biopsy figure is somewhere between 2% and 18%. Given that the recommended rate is 10%, it seems that surgeons and radiologists are collaborating well and that surgical breast biopsy is not being overused. PMID- 22305701 TI - Dramatically increased musculoskeletal ultrasound utilization from 2000 to 2009, especially by podiatrists in private offices. AB - PURPOSE: Over the past two decades, musculoskeletal (MSK) ultrasound has emerged as an effective means of diagnosing MSK pathologies. However, some insurance providers have expressed concern about increased MSK ultrasound utilization, possibly facilitated by the low cost and ready availability of ultrasound technology. The purpose of this study was to document trends in MSK ultrasound utilization from 2000 to 2009 within the Medicare population. METHODS: Source data were obtained from the CMS Physician/Supplier Procedure Summary Master Files from 2000 to 2009, and records were extracted for procedures for extremity nonvascular ultrasound. We analyzed annual volume by provider type using specialties, practice settings, and geographic regions where the studies were performed. RESULTS: In 2000, Medicare reimbursed 56,254 MSK ultrasound studies, which increased to 233,964 in 2009 (+316%). Radiologists performed the largest number of MSK ultrasound studies in 2009, 91,022, an increase from 40,877 in 2000. Podiatrists utilized the next highest number of studies in 2009, 76,332, an increase from 3,920 in 2000. Overall, private office MSK ultrasound procedures increased from 19,372 in 2000 to 158,351 in 2009 (+717%). In 2009, podiatrists performed the largest number of private office procedures (75,544) and accounted for 51.5% of the total private office growth from 2000 to 2009. Radiologist private office procedures totaled 19,894 in 2009, accounting for 9.2% of the total private office MSK ultrasound growth. CONCLUSIONS: The MSK ultrasound volume increase among nonradiologists, especially podiatrists, was far higher than that among radiologists from 2000 and 2009, with the highest growth in private offices. These findings raise concern for self-referral. PMID- 22305702 TI - Moral hazard: why consequences matter. PMID- 22305703 TI - JACR Journal Club: the University of Iowa experience. PMID- 22305704 TI - The safety attitudes questionnaire in radiology: a cornerstone of a successful quality program. PMID- 22305705 TI - Optimizing CT dose and image quality for radiotherapy patients. PMID- 22305707 TI - Does diabetes hide osteoarthritis pain? AB - Clinical practice and research efforts related to the highly prevalent and disabling disease, osteoarthritis (OA), have long been hampered by an inadequate case definition. Much of the difficulty is due to a lack of agreement between X rays evidence of OA and a patient's report of pain at that site. Such discordance between reported pain and radiographic evidence of OA has been attributed to several factors. This paper proposes another possible explanation, for at least a portion of such patients. It is hypothesized that an insidiously increasing diabetic neuropathy, particularly in the lower extremity, while first causing some pain, may gradually inhibit the ability to feel pain which might have otherwise been reported by those patients without neuropathy. Many of these patients with early stage glucose dysmetabolism will proceed to develop overt type 2 diabetes; however, the pain-inhibiting neuropathy caused by glucose metabolism dysfunction may manifest long before such a diagnosis. The high prevalence of diabetes and pre-diabetic conditions, especially among the aged population, could mean that a substantial number of individuals with osteoarthritis will have both diseases to varying degrees over time. Validating and quantifying this hypothesized association would be useful to millions of persons and would significantly impact both research and clinical practice dealing with these major diseases of older persons. PMID- 22305708 TI - Crisis-repair sequences - considerations on the classification and assessment of breaches in the therapeutic relationship. AB - BACKGROUND: Recent research indicates that temporary deteriorations of variables monitored continuously in the course of the therapeutic relationship are important characteristics of psychotherapeutic change. These so-called rupture repair episodes were assessed by different authors using different mathematical methods. METHODS: The study deals with the criteria for identifying rupture repair episodes that have been established in previous studies. It proposes modifications of these criteria which prospectively could make it possible to identify rupture-repair episodes more precisely and consistently. The authors developed an alternative criterion. This criterion is able to include crisis patterns which had not been considered before, as well as to characterize the length of the crises. As a sample application, the different criteria were applied to continuously measured assessments of the therapeutic interaction in psychodynamic therapy courses (ten shorter processes and one long-term therapy). RESULTS: The analysis revealed that the number of the identified rupture-repair episodes differed depending on the criterion that was used. Considerably more crises were identified with the newly developed criterion. The authors developed a classification of crisis patterns. They distinguished five patterns of crises and their resolution in therapy processes and ascertained the frequency of distribution. The most frequent pattern was the simple V-shape. The second most common pattern was a decline over more than one session with a sudden repair. The longest downward trend comprised a period of six sessions. CONCLUSIONS: The findings of the study give insight into basic mechanisms of change within the therapeutic relationship. A phenomenological discussion of how a crisis is defined is useful to create a methodological approach to the operationalization of crises, to differentiate specific characteristics and to specifically link these characteristics to the outcome in future studies. The methodological deliberations might be applyable to different research areas where the analysis of fluctuations in a variable of interest over time is relevant. PMID- 22305709 TI - Localized calcification of hydrophilic acrylic intraocular lenses in association with intracameral injection of gas. PMID- 22305710 TI - Evidence based workplace interventions to promote breastfeeding practices among Pakistani working mothers. AB - BACKGROUND AND AIM: Breastfeeding is an essential source of nutrition for young babies; however, it is challenging for employed mothers to continue breastfeeding with employment, especially if workplace support is minimal or missing. In Pakistan, from 1983 to 2008, the prevalence of breastfeeding at 6 months has decreased from 96% to 31%. In this region, workplace barriers have been reported as one of the reasons that result in early cessation of breastfeeding among working mothers. This paper aims at reviewing global literature to explore workplace interventions that can promote the breastfeeding practices among working mothers in Pakistan. METHODS: A literature search of peer reviewed databases, including CINHAL (1980-2009), MEDLINE (1980-2009), Pub Med (1980 2009), Springer Link (1980-2008), and Cochrane Database of Systematic Reviews (3rd quarter, 2008), was undertaken. Considering the pre-set inclusion and exclusion criteria, out of more than 500 literature sources, 50 were shortlisted and reviewed. RESULTS: A review of global literature revealed that in order to promote breastfeeding practices among employed mothers, the most powerful workplace interventions include: educating working mothers about management of breastfeeding with employment; enhancing employers' awareness about benefits of breastfeeding accommodation at workplace; arranging physical facilities for lactating mothers (including privacy, childcare facilities, breast pumps, and breast milk storage facilities); providing job-flexibility to working mothers; and initiating mother friendly policies at workplace that support breastfeeding. CONCLUSION: In Pakistani workplace settings, where little attention is paid to sustain breastfeeding practices among working mothers, there is a need to initiate lactation support programmes. These programmes can be made effective by implementing composite interventions at the level of breastfeeding working mothers, employers, and workplace. PMID- 22305711 TI - Lost tribe? Awareness of oral and maxillofacial surgery (OMFS) among the general public. AB - OMFS has important links with other disciplines in medicine and dentistry. Therefore it is important that people are aware of this speciality. A study was devised to determine the awareness of OMFS among the general public and to improve their understanding. A questionnaire was distributed among the participants attending a dental practice. 100 participated and the mean age was 42.5 years. Only 17% were aware of OMFS. 96% recognised the duty of OMFS practitioner while 74% did agree dual qualification was necessary. 68% identified hospital as the main place of work and 61% thought that the training was 5-6 years long. This study confirms that awareness of OMFS among general public remains low and much needs to be done to improve it. PMID- 22305712 TI - Synthetic RNA switches as a tool for temporal and spatial control over gene expression. AB - The engineering of biological systems offers significant promise for advances in areas including health and medicine, chemical synthesis, energy production, and environmental sustainability. Realizing this potential requires tools that enable design of sophisticated genetic systems. The functional diversity of RNA makes it an attractive and versatile substrate for programming sensing, information processing, computation, and control functions. Recent advances in the design of synthetic RNA switches capable of detecting and responding to molecular and environmental signals enable dynamic modulation of gene expression through diverse mechanisms, including transcription, splicing, stability, RNA interference, and translation. Furthermore, implementation of these switches in genetic circuits highlights the potential for building synthetic cell systems targeted to applications in environmental remediation and next-generation therapeutics and diagnostics. PMID- 22305713 TI - Third trimester fetal pulmonary artery Doppler blood flow velocity characteristics following prenatal selective serotonin reuptake inhibitor (SSRI) exposure. AB - BACKGROUND: There have been contradictory reports on the risks of persistent pulmonary hypertension (PPHN) in infants exposed to SSRIs in utero. However, there has been no assessment of fetal pulmonary arterial dynamics in such pregnancies. AIMS AND SUBJECTS: To measure fetal right pulmonary artery (RPA) variables using Doppler ultrasound at 36 weeks gestation in fetuses of mothers taking SSRI antidepressants (n=23) and in a control, normal pregnancy group (n=35). OUTCOME MEASURES: At 36 weeks gestation, Doppler ultrasound estimates of Pulsatility Index (PI), Resistance Index (RI), vessel diameter, peak systolic velocity, mean velocity and volume flow were obtained from the fetal right pulmonary artery in a morning session (~0830), before the SSRI mothers took their daily drug dose and in an afternoon session (~1300). Venous blood was drawn at 5 time points across the day (~08:30AM, ~10:30AM, ~13:00PM, ~13:45PM, and ~15:00PM) from the SSRI treated mothers for measurement of plasma SSRI concentration using high performance liquid chromatography tandem mass spectrometry. RESULTS: There were no differences in the RPA Doppler measures between the control and SSRI exposed fetuses. However 8 of the 23 latter fetuses experience transient respiratory difficulties at birth and, in these RPA flow was significantly higher than in the SSR-exposed fetuses without respiratory problems. There were, however, no differences in RPA PI and RI between the 2 groups. CONCLUSIONS: In SSRI-exposed infants with transient postnatal respiratory difficulties, fetal RPA flow in increased, likely due to partial constriction of the ductus arteriosus. However, this was not associated with PPHN. PMID- 22305714 TI - Regulatory T cell migration during an immune response. AB - CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells migrate into both inflammatory sites and draining lymph nodes (LNs) during an immune response, and have unique and overlaping functions in each location. Current studies suggest that Treg cells in draining LNs and inflamatory sites may not simply be a division of labor, but rather Treg cells migrate in a coordinated fashion between peripheral tissues and draining LNs. Trafficking between inflammatory sites and draining LNs is not only crucial for Treg cells to act, but also for them to acquire optimal immune regulatory activities. Furthermore, recent work has revealed that T helper (Th)1, Th2 and Th17 cell master transcription factors control Treg cell function by regulating genes important for Treg cell migration and suppression, and consequently affect disease pathogenesis. PMID- 22305715 TI - Biomimetic mineralization: long-term observations in patients with dentin sensitivity. AB - OBJECTIVE: Cervical tooth erosion is increasingly observed among adults and frequently associated with dentin sensitivity (DS). This study evaluated the effectiveness on DS of a biomimetic mineralization system (BIMIN) in comparison to the current standard treatment (Gluma((r)) Desensitizer, Gluma). METHODS: In this single-blind, 2-arm study, 40 patients with confirmed cervical DS were randomized to either the test group or the positive control group. A Visual Analog-Scale (VAS) was used to assess DS following stimulation of the exposed dentin with a 2-s air blast. Assessments were made at baseline (pre-treatment), 2 days, 4, 8 and 12 weeks, and 12 months after treatment. Two-stage replicas were obtained from the treated teeth and gold sputtered at baseline, and 2 days, 3 and 12 months after treatment. Surface topography of the treated cervical lesions and occlusion of dentinal tubules were investigated using scanning electron microscopy (SEM). RESULTS: Both treatments led to a statistically significant reduction (P<0.0001) in DS that persisted over the entire 12-month observation period. Differences in DS between the treatments were not statistically significant. SEM photomicrographs demonstrated that a mineral layer concealed the dentinal tubules in the test group. In contrast, numerous dentinal tubules remained visible in cervical defects that were treated with Gluma. SIGNIFICANCE: A biomimetic mineralization kit was successfully used to treat patients exhibiting DS. The effect was similar to using Gluma, and was likely the result of the deposition of an enamel-like layer on the exposed cervical dentin. PMID- 22305717 TI - Both El Tor and classical cholera toxin bind blood group determinants. AB - Cholera is a disease which shows a clear blood group profile, with blood group O individuals experiencing the most severe symptoms. For a long time, the cholera toxin has been suspected to be the main culprit of this blood group dependence. Here, we show that both El Tor and classical cholera toxin B-pentamers do indeed bind blood group determinants (with equal affinities), using Surface Plasmon Resonance and NMR spectroscopy. Together with previous structural data, this confirms our earlier hypothesis as to the molecular basis of cholera blood group dependence, with an interesting twist: the shorter blood group H-determinant characteristic of blood group O individuals binds with similar binding affinity compared to the A-determinant, however, with different kinetics. PMID- 22305716 TI - Antibacterial amorphous calcium phosphate nanocomposites with a quaternary ammonium dimethacrylate and silver nanoparticles. AB - OBJECTIVES: Calcium and phosphate ion-releasing resin composites are promising for remineralization. However, there has been no report on incorporating antibacterial agents to these composites. The objective of this study was to develop antibacterial and mechanically strong nanocomposites incorporating a quaternary ammonium dimethacrylate (QADM), nanoparticles of silver (NAg), and nanoparticles of amorphous calcium phosphate (NACP). METHODS: The QADM, bis(2 methacryloyloxyethyl) dimethylammonium bromide (ionic dimethacrylate-1), was synthesized from 2-(N,N-dimethylamino)ethyl methacrylate and 2-bromoethyl methacrylate. NAg was synthesized by dissolving Ag 2-ethylhexanoate salt in 2 (tert-butylamino)ethyl methacrylate. Mechanical properties were measured in three point flexure with bars of 2 mm*2 mm*25 mm (n=6). Composite disks (diameter=9 mm, thickness=2 mm) were inoculated with Streptococcus mutans. The metabolic activity and lactic acid production of biofilms were measured (n=6). Two commercial composites were used as controls. RESULTS: Flexural strength and elastic modulus of NACP+QADM, NACP+NAg, and NACP+QADM+NAg matched those of commercial composites with no antibacterial property (p>0.1). The NACP+QADM+NAg composite decreased the titer counts of adherent S. mutans biofilms by an order of magnitude, compared to the commercial composites (p<0.05). The metabolic activity and lactic acid production of biofilms on NACP+QADM+NAg composite were much less than those on commercial composites (p<0.05). Combining QADM and NAg rendered the nanocomposite more strongly antibacterial than either agent alone (p<0.05). SIGNIFICANCE: QADM and NAg were incorporated into calcium phosphate composite for the first time. NACP+QADM+NAg was strongly antibacterial and greatly reduced the titer counts, metabolic activity, and acid production of S. mutans biofilms, while possessing mechanical properties similar to commercial composites. These nanocomposites are promising to have the double benefits of remineralization and antibacterial capabilities to inhibit dental caries. PMID- 22305718 TI - Chronic cough: new perspectives in its diagnosis and treatment. PMID- 22305719 TI - Insights into the mechanisms mediating hyperglycemic and stressogenic outcomes in rats treated with monocrotophos, an organophosphorus insecticide. AB - The present investigation provides mechanistic insights into the hyperglycemic and stressogenic effects of monocrotophos, an organophosphorus insecticide. Pre treatment of rats with mifepristone (glucocorticoid receptor antagonist) prevented induction of liver tyrosine aminotransferase activity (TAT), but was ineffective in attenuating hyperglycemia induced by monocrotophos. Pre-treatment with propranolol (beta-adrenergic receptor antagonist) and phentolamine (alpha adrenergic receptor antagonist) were effective in abrogating monocrotophos induced hyperglycemia. Interestingly, while propranolol offered partial protection against hyperglycemia, phentolamine completely abolished the same. However, monocrotophos-induced hyperlactacidemia was completely abolished by propranolol. Both the adrenoreceptor antagonists, however, failed to attenuate the stressogenic potential of monocrotophos. Hyperglycemia and hyperlactacidemia induced by monocrotophos were abolished by pre-treatment with atropine. Exogenous epinephrine was associated with hyperglycemia and hyperlactacidemia. The impact of adrenergic antagonists on epinephrine-induced hyperglycemia and hyperlactacidemia were remarkably similar to that of monocrotophos-induced hyperglycemia and hyperlactacidemia. Further, hydrazine sulfate (a gluconeogenesis inhibitor) abolished hyperglycemia in monocrotophos-treated rats. From our data, it can be hypothesized that excessive stimulation of adrenoreceptors, probably elicited by increased plasma epinephrine, mediates hyperglycemic outcomes induced by monocrotophos. Pattern of changes in plasma lactate suggests that beta-adrenergic activation mediates monocrotophos-induced hyperlactacidemia, while alpha-adrenergic receptor mediates lactate utilization, leading to hyperglycemia. Induction of liver TAT activity is attributable to glucocorticoid receptor activation as a result of hypercorticosteronemia. PMID- 22305720 TI - Feed-forward mechanisms: addiction-like behavioral and molecular adaptations in overeating. AB - Food reward, not hunger, is the main driving force behind eating in the modern obesogenic environment. Palatable foods, generally calorie-dense and rich in sugar/fat, are thus readily overconsumed despite the resulting health consequences. Important advances have been made to explain mechanisms underlying excessive consumption as an immediate response to presentation of rewarding tastants. However, our understanding of long-term neural adaptations to food reward that oftentimes persist during even a prolonged absence of palatable food and contribute to the reinstatement of compulsive overeating of high-fat high sugar diets, is much more limited. Here we discuss the evidence from animal and human studies for neural and molecular adaptations in both homeostatic and non homeostatic appetite regulation that may underlie the formation of a "feed forward" system, sensitive to palatable food and propelling the individual from a basic preference for palatable diets to food craving and compulsive, addiction like eating behavior. PMID- 22305721 TI - The development of decision limits for the implementation of the GH-2000 detection methodology using current commercial insulin-like growth factor-I and amino-terminal pro-peptide of type III collagen assays. AB - BACKGROUND: The GH-2000 project developed a method for detecting GH misuse based on the measurement of insulin-like growth factor-I (IGF-I) and the amino-terminal pro-peptide of type III collagen (P-III-NP). The objective of this study was to develop decision limits for the GH-2000 score to detect GH misuse in elite athletes using two currently available commercial assays for each analyte. STUDY DESIGN: SUBJECTS: 404 male (mean age 23.9 yrs, range 12-37 yrs) and 94 female elite athletes (mean age 24.5 yrs, range 18-34 yrs) participated. Blood samples were collected according to World Anti-Doping Agency (WADA) guidelines at various sporting events including 238 samples collected as part of the UK Anti-Doping Testing Programme. Laboratory analysis: IGF-I was measured by Siemens Immulite IGF-I assay and Immunotech A15729 IGF-I IRMA. P-III-NP was measured by RIA-gnost P-III-P and the UniQTM PIIINP RIA. STATISTICAL ANALYSIS: The GH-2000 score decision limits were developed through the analysis of the elite athlete samples. RESULTS: For males and females separately, the distributions of GH-2000 scores were consistent with Normal distributions. Using a specificity of 99.99% new decision limits were determined which included an allowance for uncertainty associated with calculations based on a finite sample size. One outlier was identified with results incompatible with normal physiology and tested positive with the current isoform GH test. CONCLUSIONS: We have developed decision limits using currently available commercial assays to measure IGF-I and P-III-NP in elite athletes. This should allow the introduction of a test for GH misuse based on the measurement of these GH sensitive biomarkers. PMID- 22305722 TI - Magnetic resonance imaging in evaluating workers' compensation patients. AB - PURPOSE: We studied the utility of magnetic resonance imaging (MRI) studies for workers' compensation patients with hand conditions in which the referring doctor obtained the images. We compared the MRI findings with the eventual clinical findings. We also investigated the approximate cost of these MRI studies. METHODS: We retrospectively reviewed the charts of all workers' compensation patients seen in a hand and upper extremity practice over the course of 3 years. We selected patients who had MRI studies of the affected upper extremities before referral to the senior author (G.R.). We reviewed the charts for information regarding demographics, referral diagnoses, MRI diagnoses made by the radiologist, the area of the upper extremity studied, and eventual clinical diagnoses by the senior author. We made a determination as to whether a hand surgeon could have adequately diagnosed and treated the patients' conditions without the imaging studies. We also investigated the cost associated with these MRIs. RESULTS: We included 62 patients with a total of 67 MRI scans in this study. The MRI studies did not contribute to clinically diagnosing the patients' conditions in any of the cases we reviewed. The hand surgeon's clinical diagnosis disagreed with the radiologist's MRI diagnosis in 63% of patients. The MRI was unnecessary to arrive at the clinical diagnosis and did not influence the treatment offered for any of the 62 patients. The total cost for the 67 non contrast MRI studies was approximately $53,000. CONCLUSIONS: Costly imaging studies are frequently done to determine the validity of a patient's reported problems; unfortunately, these tests are frequently unnecessary and waste resources. Magnetic resonance imaging scans may not be the standard for accurate diagnosis and can misdirect care. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III. PMID- 22305723 TI - Sigmoid notch reconstruction and limited carpal arthrodesis for a severely comminuted distal radius malunion: case report. AB - We present the case of a young patient with a severely comminuted, malunited, intra-articular distal radius fracture and complete disruption of the sigmoid notch. We reconstructed the malunited distal radioulnar joint by osteotomy and repositioning the displaced sigmoid notch fragments through a combined dorsal and volar approach. At the same time, we carried out a radioscapholunate arthrodesis with distal scaphoid excision. We used a free vascularized corticoperiosteal flap from the medial femoral condyle to span the massive bone defect in the radius to obtain union. At the 2.5-year follow-up, the patient had essentially normal function of the distal radioulnar joint (painless, with 85 degrees of active pronation and 75 degrees of supination). He resumed work as a bricklayer without limitations. We conclude that sigmoid notch reconstruction by osteotomy is worthwhile in the setting of malunited distal radius whether or not the radiocarpal joint is reconstructable. PMID- 22305724 TI - Therapeutic modalities--an updated review for the hand surgeon. AB - The number of therapeutic modalities available to the hand surgeon has greatly increased over the past several decades. A field once predicated only on heat, massage, and cold therapy now uses electrical stimulators, ultrasound, biofeedback, iontophoresis, phonophoresis, mirror therapy, lasers, and a number of other modalities. With this expansion in choices, there has been a concurrent effort to better define which modalities are truly effective. In this review, we aim to characterize the commonly used modalities and provide the evidence available that supports their continued use. PMID- 22305725 TI - Recurrent or persistent cubital tunnel syndrome. PMID- 22305726 TI - Studies in flexor tendon reconstruction: biomolecular modulation of tendon repair and tissue engineering. AB - The Andrew J. Weiland Medal is presented each year by the American Society for Surgery of the Hand and the American Foundation for Surgery of the Hand for a body of work related to hand surgery research. This essay, awarded the Weiland Medal in 2011, focuses on the clinical need for flexor tendon reconstruction and on investigations into flexor tendon biology. Reconstruction of the upper extremity is limited by 2 major problems after injury or degeneration of the flexor tendons. First, adhesions formed after flexor tendon repair can cause decreased postoperative range of motion and hand function. Second, tendon losses can result from trauma and degenerative diseases, necessitating additional tendon graft material. Tendon adhesions are even more prevalent after tendon grafting; therefore these 2 problems are interrelated and lead to considerable disability. The total costs in terms of disability and inability to return to work are enormous. In this essay, published work from the past 12 years in our basic science laboratory is summarized and presented with the common theme of using molecular techniques to understand the cellular process of flexor tendon wound healing and to create substances and materials to improve tendon repair and regeneration. These are efforts to address 2 interrelated and clinically relevant problems that all hand surgeons face in their practice. PMID- 22305727 TI - Distal humerus fractures: handling of the ulnar nerve. PMID- 22305728 TI - Rapid resorption of calcium sulfate and hardware failure following corrective radius osteotomy: 2 case reports. AB - Bone substitutes are being increasingly used and may avert the need for autogenous bone graft in orthopedic surgery. Thus it is important to note complications that occur with them to better understand the limitations. We report on early mechanical failure of injectable calcium sulfate leading to implant failure in 2 elderly patients who had corrective osteotomies for malunited distal radius fractures. We hypothesize that these occurred because there was inadequate new bone formation to replace the resorbing bone substitute. We advise caution when using bone substitutes in patients with expected delayed fracture healing. PMID- 22305729 TI - The effects of screw length on stability of simulated osteoporotic distal radius fractures fixed with volar locking plates. AB - PURPOSE: Volar plating for distal radius fractures has caused extensor tendon ruptures resulting from dorsal screw prominence. This study was designed to determine the biomechanical impact of placing unicortical distal locking screws and pegs in an extra-articular fracture model. METHODS: We applied volar-locking distal radius plates to 30 osteoporotic distal radius models. We divided radiuses into 5 groups based on distal locking fixation: bicortical locked screws, 3 lengths of unicortical locked screws (abutting the dorsal cortex [full length], 75% length, and 50% length to dorsal cortex), and unicortical locked pegs. Distal radius osteotomy simulated a dorsally comminuted, extra-articular fracture. We determined each construct's stiffness under physiologic loads (axial compression, dorsal bending, and volar bending) before and after 1,000 cycles of axial conditioning and before axial loading to failure (2 mm of displacement) and subsequent catastrophic failure. RESULTS: Cyclic conditioning did not alter the constructs' stiffness. Stiffness to volar bending and dorsal bending forces were similar between groups. Final stiffness under axial load was statistically equivalent for all groups: bicortical screws (230 N/mm), full-length unicortical screws (227 N/mm), 75% length unicortical screws (226 N/mm), 50% length unicortical screws (187 N/mm), and unicortical pegs (226 N/mm). Force at 2-mm displacement was significantly less for 50% length unicortical screws (311 N) compared with bicortical screws (460 N), full-length unicortical screws (464 N), 75% length unicortical screws (400 N), and unicortical pegs (356 N). Force to catastrophic fracture was statistically equivalent between groups, but mean values for pegs (749 N) and 50% length unicortical (702 N) screws were 16% to 21% less than means for bicortical (892 N), full-length unicortical (860 N), and 75% length (894 N) unicortical constructs. CONCLUSIONS: Locked unicortical distal screws of at least 75% length produce construct stiffness similar to bicortical fixation. Unicortical distal fixation for extra-articular distal radius fractures should be entertained to avoid extensor tendon injury because this technique does not appear to compromise initial fixation. CLINICAL RELEVANCE: Using unicortical fixation during volar distal radius plating may protect extensor tendons without compromising fixation. PMID- 22305730 TI - Metacarpophalangeal joint hyperextension and the treatment of thumb basilar joint arthritis. PMID- 22305731 TI - Graphs, tables, and figures in scientific publications: the good, the bad, and how not to be the latter. AB - Graphs, figures, and tables can save readers time and energy, aid their understanding of an article, and reduce the word count of the main text. However, many graphics submitted to and published in scientific journals fail to meet their potential and include mistakes that jeopardize their clarity. Many formats are available for presenting data, as well as a variety of techniques for enhancing interpretability. When the appropriate format is used to depict data, it conveys the greatest amount of information in the clearest fashion, complements the text, and deepens readers' understanding. The aims of this article are to draw attention to the necessity of well-constructed graphs, tables, and figures in scientific publications, and to show how to create them. PMID- 22305732 TI - e-Prescribe meaningful use requirement. PMID- 22305733 TI - Conservative management of Dieterich disease: case report. AB - Dieterich disease is characterized by avascular necrosis of the metacarpal head. The recent literature has described surgical management of this condition relatively soon after its presentation. We present a case treated conservatively with a satisfactory outcome at 28 months. PMID- 22305734 TI - Reconstruction of the coronoid process using a fragment of discarded radial head. AB - Maintaining ulnohumeral stability can be difficult when either the coronoid is too fragmented for primary repair or operative delay makes repair difficult or impossible. In addition to ligament repair, restoration of radiocapitellar contact using radial head arthroplasty, and hinged external fixation, reconstruction of the coronoid using a fragment of the discarded radial head-a technique described in this report-can help restore elbow stability and function. PMID- 22305735 TI - Results of a method of 4-corner arthrodesis using headless compression screws. AB - PURPOSE: To evaluate the functional and radiographic results of a scaphoid excision and four-corner arthrodesis technique using percutaneous headless compression screws. METHODS: A cohort of 33 patients, mean age 51 (range, 20-72) years, was treated for scapholunate advanced collapse (19), scaphoid nonunion advanced collapse (12), midcarpal instability (1), and Preiser disease (1). After scaphoid excision and removal of cartilage and subchondral bone in the midcarpal joint through a limited arthrotomy, capitolunate fixation was achieved with a percutaneous, transmetacarpal Acutrak screw (Acumed LLC, Hillsboro, OR), and triquetrohamate fixation was done with a percutaneous screw. Scaphoid was used as a bone graft. The average follow-up time was 8 months (n = 32; range, 6-64 mo). RESULTS: Union occurred in 31 of 33 wrists (94%). One of the 33 patients had total wrist arthrodesis. Average total active flexion-extension arc was 71 degrees after surgery and 83 degrees before surgery. The postoperative carpal height averaged 0.47 compared to preoperative values of 0.45. The percentage of grip strength significantly improved from 41% before surgery to 80% after surgery. Postoperative mean verbal numerical rating scale pain score was less than 1, statistically better than the preoperative score of 7. Twenty-five of 33 patients were completely pain free. The average postoperative Mayo wrist score was 74, a significant improvement over the preoperative average of 40. Final Disabilities of the Arm, Shoulder, and Hand scores averaged 13 (n = 32; range, 0 49). CONCLUSIONS: These results were comparable to or better than the results of previously published techniques in terms of fusion rates, alleviation of pain, grip strength, range of motion; Mayo wrist score; and Disabilities of the Arm, Shoulder, and Hand questionnaire score. The technique exploits the theoretical advantages of strong compression between carpals while avoiding a screw-head sized hole in the lunate articular cartilage and preserving the dorsal capsular ligament attachments to the triquetrum. PMID- 22305736 TI - Traversing the neurovascular bundle at the level of the metacarpophalangeal joint in palmar fasciectomy for Dupuytren disease. PMID- 22305737 TI - Platelet-rich plasma. PMID- 22305738 TI - Cutaneous mucormycosis of the upper extremity in an immunocompetent host: case report. AB - Cutaneous mucormycosis, a relatively common infection in immunocompromised patients, remains rare in the immunocompetent patient outside the setting of major trauma. We report a case of an immunocompetent patient who developed left upper extremity Rhizopus infection following arterial puncture. Treatment included surgical debridement, liposomal amphotericin B, and hyperbaric oxygen wound therapy; the patient recovered fully. A review of the literature of cases of upper extremity Mucor infection is included for context. We feel that a high degree of suspicion for Mucor infection is warranted in patients with the described risk factors who do not respond to first-line antibiotics. PMID- 22305739 TI - Nonoperative management of scleroderma of the hand with tadalafil and subatmospheric pressure wound therapy: case report. AB - Scleroderma, or systemic sclerosis (SS), is an autoimmune disease leading to ischemic fibrosis and widespread collagen deposition, invariably affecting the hands. Optimized medical management remains the mainstay of therapy for SS. Surgery can be considered in refractory or severely disabling cases. However, microvascular insufficiency and fibrosis can lead to wound complications and, ultimately, amputation. We present the case of a 61-year-old man with a known history of scleroderma who presented with pain, chronic infection, and ulcerations in the left hand. Initially, amputation seemed a reasonable intervention. After medical optimization with tadalafil, his ulcerations persisted. Instead of amputation, we applied a subatmospheric pressure wound therapy device to his hand. In 4 months, his wounds had healed, there was no evidence of infection, and no digits were amputated. PMID- 22305740 TI - Treatment of a Bennett fracture using tension band wiring. AB - PURPOSE: To describe and assess a tension band wiring technique for the treatment of Bennett fractures and to compare this technique of open reduction and internal fixation versus closed reduction and percutaneous pinning. METHODS: From July 2005 to April 2008, we treated 56 Bennett fractures in 56 patients using tension band wiring. The mean age of the patients was 32 years. There were 37 dominant hands and 19 nondominant hands. The mean time between the injury and operation was 5 days. In this open tension band fixation group, the mean joint surface involvement was 39%, and all injuries were associated with carpometacarpal joint subluxation. At final follow-up, we assessed the thumbs for range of motion and assessed the hands for pinch and grip strength. For comparison, we also included 21 patients who were treated using closed reduction and percutaneous pin fixation from January 2003 to May 2005. RESULTS: We noted no fixation failures in the open reduction internal fixation group. Radiographic fracture healing was achieved in all patients at a mean time of 4 weeks. Patient follow-up averaged 39 months. At final follow-up, the mean extension-flexion arc of the first carpometacarpal joint was 49 degrees . Mean thumb abduction was 82 degrees and mean pinch and grip strength of the injured hands were 7.4 and 43.0 kg, respectively. There were no significant differences between groups regarding the extension-flexion arc of the first carpometacarpal joint and grip strength. The 2 groups were similar in thumb abduction and pinch strength. CONCLUSIONS: Open tension band wiring is a useful and reliable technique and presents another fixation option for the treatment of Bennett fractures. PMID- 22305741 TI - Arthroscopic treatment of peripheral triangular fibrocartilage complex tears with the deep fibers intact. AB - PURPOSE: We describe a variant of triangular fibrocartilage complex (TFCC) tears in which the superficial fibers attaching to the ulnar capsule are torn, with preservation of deep fibers inserting on the fovea. We present the clinical and magnetic resonance imaging findings and the results of arthroscopic repair in patients with this injury. METHODS: Twenty-nine wrists were treated arthroscopically for peripheral TFCC tears with outside-in suture repair of the TFCC to the ulnar capsule. A retrospective review of all cases was performed to assess the physical examination, magnetic resonance imaging, and intraoperative findings. Patients were evaluated at greater than 1 year with range of motion, grip strength, standard outcome measures, and a survey assessing return to work and sports. RESULTS: Before surgery, all patients had complaints of ulnar-sided wrist pain with a stable distal radioulnar joint on examination. Twenty-six wrists (90%) were available for follow-up at a mean of 31 months. There was one repeat surgery, a re-tear that required revision TFCC repair. The preoperative visual analog scale and Disabilities of the Arm, Shoulder, and Hand scores improved from 5 and 38 to 1 and 9, respectively, at final follow-up. Side-to-side comparisons demonstrated no measurable loss in motion or grip strength. There were no cases of distal radioulnar joint instability at final follow-up. Of 11 high-level athletes in the total cohort, 7 (64%) were able to return to sports, including all of those in racquet sports; however, athletes who bore weight through their hands were unable to return to their sporting activity. CONCLUSIONS: Tears of the TFCC superficial fibers with the deep fibers intact present with ulnar-sided wrist pain but without distal radioulnar joint instability. The results of outside-in repair of the articular disk back to the ulnar capsule demonstrated improvement in pain and function with no measurable objective losses. Return to sport was variable and appeared worse for those who bear weight through the hands. PMID- 22305742 TI - Repeat operation for treatment of persistent pudendal nerve entrapment after pudendal neurolysis. AB - STUDY OBJECTIVES: To describe a new approach to transgluteal pudendal neurolysis and transposition and to review the outcome in 10 patients who underwent repeat operation because of persistent pudendal neuralgia after failing to improve after initial surgical decompression. DESIGN: Retrospective analysis (Canadian Task Force classification II-3). SETTING: Academic chronic pelvic pain practice at St. Joseph's Hospital and Medical Center in Phoenix, Arizona. PATIENTS: Women and men with persistent pudendal neuralgia after undergoing transgluteal pudendal neurolysis and transposition. INTERVENTION: Transgluteal decompression of the pudendal nerve was performed in all 10 patients. In brief, a transgluteal incision was made, and the pudendal nerve was identified via a nerve integrity monitoring system. Adhesiolysis was performed from the piriformis muscle to the distal Alcock canal using a Zeiss NC-4 surgical microscope. The nerve was then enclosed in NeuraWrap Nerve Protector and coated with activated platelet-rich plasma. An ON-Q PainBuster catheter was place along the nerve into the Alcock canal, and 0.5% bupivacaine was infused at 2 mL/hr. The sacrotuberous ligament was repaired using an Achilles or gracillis cadaver ligament. The overlying subcutaneous tissue and skin were then closed. MEASUREMENTS AND MAIN RESULTS: From June 2008 to March 2010, 10 consecutive patients (7 women and 3 men; age range, 29-81 years) underwent repeat operation with transgluteal decompression of the pudendal nerve. Neuropathic pain was unilateral (n = 8) or bilateral (n = 2), in the clitoris or penis (30%), vulva or scrotum (70%), perineum (40%), and rectum (50%). Of the 10 patients, 1 patient was lost to follow-up. Mean follow-up was 23 months. Eight of 9 patients reported global improvement, with 2 patients reporting complete resolution of symptoms. One patient reported no change. Pain, as measured using an 11-point numerical scale, improved from a mean of 7.2 to 4.0 (p = .02), with 5 patients reporting clinically significant improvement (change, >=2). Comfortable sitting or maximum time that the patient was able to sit without exacerbation of pain improved in 8 patients, with a change in median time of 5 to 45 minutes (p = .008). Change in the ability to sit correlated well with patient-reported global improvement (correlation coefficient, 0.86). No patient experienced worsening of symptoms. CONCLUSION: Patients with persistent pudendal neuralgia after surgical decompression may benefit from repeat operation via our novel approach. Ability to sit correlates well with reported improvement due to surgery. PMID- 22305743 TI - The use of skills inventories to assess and grade practice: Part 2--evaluation of assessment strategy. AB - This paper evaluates the introduction of an assessment tool to grade clinical competence in post-registration critical care courses using a skills-based assessment strategy. An audit of skills assessors was conducted alongside an analysis of theory and practice marks. Findings showed marks awarded for practice were generally higher than those awarded for theory which may be expected in a clinically-based profession. Whilst grading of practice requires further exploration, our experience shows that competence can be defined, measured and the resultant marks incorporated into a degree classification with relative ease. Consistency between assessors remains an issue but can be assisted by the use of clear skills templates and a user-friendly grading tool. PMID- 22305744 TI - Numeracy skills of undergraduate entry level nurse, midwife and pharmacy students. AB - BACKGROUND: The ability of healthcare professionals to perform basic numeracy and therefore dose calculations competently is without question. Research has primarily focused on nurses, and to a lesser extent doctors, ability to perform this function with findings highlighting poor aptitude. Studies involving pharmacists are few but findings are more positive than other healthcare staff. AIMS: To determine first year nursing, midwifery and pharmacy students ability to perform basic numeracy calculations. METHOD: All new undergraduate entrants to nursing, midwifery and pharmacy sat a formative numeracy test within the first two weeks of their first year of study. RESULTS: Test results showed that pharmacy students significantly outperformed midwifery and nursing students on all questions. In turn midwifery students outperformed nurses, although this did not achieve significance. When looking at each cohorts general attitude towards mathematics, pharmacy students were more positive and confident compared to midwifery and nursing students. CONCLUSION: Pharmacy students expressed greater levels of enjoyment and confidence in performing mathematics and correspondingly showed the greatest proficiency. In contrast nurse, and to a lesser extent midwifery students showed poor performance and low confidence levels. PMID- 22305745 TI - Additive activation of glucokinase by the bifunctional enzyme 6-phosphofructo-2 kinase/fructose-2,6-bisphosphatase and the chemical activator LY2121260. AB - The glucose phosphorylating enzyme glucokinase plays a crucial role in stimulus secretion coupling in pancreatic beta cells and in glucose metabolism in liver. Glucose mediates a shift of the enzyme's conformational equilibrium towards the closed conformation with high glucokinase activity. Further activation of glucokinase is endogenously mediated by interaction with the bisphosphatase domain (FBPase-2) of the bifunctional enzyme 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFK-2/FBPase-2) and can be achieved also by a new class of glucokinase activators (GKA), chemical compounds that might be suited for type 2 diabetes therapy. While FBPase-2 increased only the phosphorylating capacity of glucokinase, the GKA LY2121260 augmented in addition the affinity of glucokinase for glucose. PFK-2/FBPase-2 but not LY2121260 antagonized glucokinase inhibition by the competitive glucokinase inhibitor mannoheptulose at increasing glucose concentrations. Interestingly, an additive activation of glucokinase was observed by use of recombinant FBPase-2 together with LY2121260. This new crucial observation could be confirmed with cellular extracts containing the glucokinase and PFK-2/FBPase-2 proteins. Addition of LY2121260 resulted in a further significant increase in glucokinase activity. Because the glucokinase-PFK 2/FBPase-2 complex was conserved under LY2121260 treatment as shown by size exclusion chromatography a concerted action of both activators towards the closed active glucokinase conformation can be anticipated. Thus, as a result of the additive effect of both activators on glucokinase activity, the largest increase of glucose-induced insulin secretion was observed in the combined presence of PFK 2/FBPase-2 and LY2121260. PMID- 22305746 TI - Arenobufagin, a bufadienolide compound from toad venom, inhibits VEGF-mediated angiogenesis through suppression of VEGFR-2 signaling pathway. AB - Angiogenesis is crucial for carcinogenesis and other angiogenic processes. Arenobufagin, one of the major components of toad venom, is a traditional Chinese medicine used for cancer therapy. It inhibits cell growth in several cancer cell lines. However, little is known about arenobufagin's anti-angiogenic activity. In this study, we showed that arenobufagin inhibited vascular endothelial growth factor (VEGF)-induced viability, migration, invasion and tube formation in human umbilical vein endothelial cells (HUVECs) in vitro. Arenobufagin also suppressed sprouting formation from VEGF-treated aortic rings in an ex vivo model. Furthermore, we found that arenobufagin blocked angiogenesis in a matrigel plugs assay. Computer simulations suggested that arenobufagin interacted with the ATP binding sites of VEGFR-2 by docking. In addition, arenobufagin inhibited VEGF induced VEGFR-2 auto-phosphorylation and suppressed the activity of VEGFR-2 mediated signaling cascades. Taken together, our findings demonstrate that arenobufagin is a specific inhibitor of VEGF-mediated angiogenesis. PMID- 22305747 TI - Antiproliferative mechanisms of action of the flavin dehydrogenase inhibitors diphenylene iodonium and di-2-thienyliodonium based on molecular profiling of the NCI-60 human tumor cell panel. AB - Flavoprotein-dependent reactive oxygen species (ROS) play a critical role in cytokine-mediated signal transduction in normal tissues and tumor cells. The flavoenzyme inhibitors diphenylene iodonium (DPI) and di-2-thienyliodonium (DTI) have been used to inhibit membrane-bound, flavoprotein-containing NADPH oxidases, including epithelial and leukocyte NADPH oxidases (Nox1-5 and Duox 1 and 2). Recent evidence suggests that DPI can decrease tumor cell proliferation; however, the molecular mechanisms involved remain poorly defined. To explore the mechanisms underlying DPI- and DTI-related tumor cell growth delay, we examined growth inhibition patterns produced by both agents in the NCI-60 tumor panel, and determined expression levels of Nox gene family members across these cell lines. Possible molecular targets were predicted using the COMPARE program. DPI was more potent than DTI (GI(50): 10nM versus 10MUM); DPI and DTI exposure produced unique patterns of growth inhibition when evaluated against the small molecule anticancer database of the National Cancer Institute. Growth inhibition profiling of DPI revealed a modest positive correlation with Nox1 levels; novel mechanisms of DPI and DTI action, including alterations in Stat, Erk1/2, and Akt pathways, were inferred by correlation with NCI-60 Affymetrix((r)) array data. Exposure of HT-29 colon cancer cells, which express Nox1, to DPI and DTI confirmed their inhibitory effects on steady state ROS levels, and demonstrated decreased Stat, Erk1/2, and Akt signaling mediated by IL-4, IL-6, IL-13, and IL-22, possibly due to a concomitant increase in tumor cell phosphatase activity. These findings suggest that DPI and DTI may act therapeutically by altering ROS-related signal transduction. PMID- 22305748 TI - Inhibition of tumor cell growth, proliferation and migration by X-387, a novel active-site inhibitor of mTOR. AB - The mammalian target of rapamycin (mTOR), is deregulated in about 50% of human malignancies and exists in two complexes: mTORC1 and mTORC2. Rapalogs partially inhibit mTORC1 through allosteric binding to mTORC1 and their efficacy is modest as a cancer therapy. A few mTOR kinase inhibitors that inhibit both mTORC1 and mTORC2 have been reported to possess potent anticancer activities. Herein, we designed and synthesized a series of pyrazolopyrimidine derivatives targeting mTOR kinase domain and X-387 was identified as a promising lead. X-387 selectively inhibited mTOR in an ATP-competitive manner while sparing a panel of kinases from the PIKK family. X-387 blocked mTORC1 and mTORC2-mediacted signaling pathway in cell lines with activated mTOR signaling and in rapamycin-resistant cells. Specifically, X-387 inhibited phosphorylation of AKT at T308, which is thought to be a target of PDK1 but not mTOR. Such activity was not due to inhibition of PI3K since X-387 did not inhibit translocation of AKT to the cell membrane. X-387 induced autophagy as observed for other mTOR inhibitors, while induced autophagy is pro-survival since concurrent inhibition of autophagy by 3 MA reinforced the antiproliferative activity of mTOR inhibitors. X-387 also inhibited cell motility, which is associated with decrease in activity of small GTPases such as RhoA, Rac1 and Cdc42. Taken together, X-387 is a promising compound lead targeting mTOR and with a wide spectrum anticancer activity among tumor cell lines. The data also underscores the complexity of the mTOR signaling pathways which are far from being understood. PMID- 22305749 TI - Purification, molecular cloning and functional characterization of HelaTx1 (Heterometrus laoticus): the first member of a new kappa-KTX subfamily. AB - Given their medical importance, most attention has been paid toward the venom composition of scorpions of the Buthidae family. Nevertheless, research has shown that the venom of scorpions of other families is also a remarkable source of unique peptidyl toxins. The kappa-KTx family of voltage-gated potassium channel (VGPC) scorpion toxins is hereof an example. From the telson of the scorpion Heterometrus laoticus (Scorpionidae), a peptide, HelaTx1, with unique primary sequence was purified through HPLC and sequenced by Edman degradation. Based on the amino acid sequence, the peptide could be cloned and the cDNA sequence revealed. HelaTx1 was chemically synthesized and functionally characterized on VGPCs of the Shaker-related, Shab-related, Shaw-related and Shal-related subfamilies. Furthermore, the toxin was also tested on small- and intermediate conductance Ca(2+)-activated K(+) channels. From the channels studied, K(v)1.1 and K(v)1.6 were found to be the most sensitive (K(v)1.1 EC(50)=9.9+/-1.6 MUM). The toxin did not alter the activation of the channels. Competition experiments with TEA showed that the toxin is a pore blocker. Mutational studies showed that the residues E353 and Y379 in the pore of K(v)1.1 act as major interaction points for binding of the toxin. Given the amino acid sequence, the predicted secondary structure and the biological activity on VGPCs, HelaTx1 should be included in the kappa-KTX family. Based on a phylogenetic study, we rearranged this family of VGPC toxins into five subfamilies and suggest that HelaTx1 is the first member of the new kappa-KTx5 subfamily. PMID- 22305750 TI - Stimulus timing-dependent plasticity in high-level vision. AB - Humans are able to efficiently learn and remember complex visual patterns after only a few seconds of exposure [1]. At a cellular level, such learning is thought to involve changes in synaptic efficacy, which have been linked to the precise timing of action potentials relative to synaptic inputs [2-4]. Previous experiments have tapped into the timing of neural spiking events by using repeated asynchronous presentation of visual stimuli to induce changes in both the tuning properties of visual neurons and the perception of simple stimulus attributes [5, 6]. Here we used a similar approach to investigate potential mechanisms underlying the perceptual learning of face identity, a high-level stimulus property based on the spatial configuration of local features. Periods of stimulus pairing induced a systematic bias in face-identity perception in a manner consistent with the predictions of spike timing-dependent plasticity. The perceptual shifts induced for face identity were tolerant to a 2-fold change in stimulus size, suggesting that they reflected neuronal changes in nonretinotopic areas, and were more than twice as strong as the perceptual shifts induced for low-level visual features. These results support the idea that spike timing dependent plasticity can rapidly adjust the neural encoding of high-level stimulus attributes [7-11]. PMID- 22305751 TI - Cholinergic enhancement of visual attention and neural oscillations in the human brain. AB - Cognitive processes such as visual perception and selective attention induce specific patterns of brain oscillations. The neurochemical bases of these spectral changes in neural activity are largely unknown, but neuromodulators are thought to regulate processing. The cholinergic system is linked to attentional function in vivo, whereas separate in vitro studies show that cholinergic agonists induce high-frequency oscillations in slice preparations. This has led to theoretical proposals that cholinergic enhancement of visual attention might operate via gamma oscillations in visual cortex, although low-frequency alpha/beta modulation may also play a key role. Here we used MEG to record cortical oscillations in the context of administration of a cholinergic agonist (physostigmine) during a spatial visual attention task in humans. This cholinergic agonist enhanced spatial attention effects on low-frequency alpha/beta oscillations in visual cortex, an effect correlating with a drug induced speeding of performance. By contrast, the cholinergic agonist did not alter high-frequency gamma oscillations in visual cortex. Thus, our findings show that cholinergic neuromodulation enhances attentional selection via an impact on oscillatory synchrony in visual cortex, for low rather than high frequencies. We discuss this dissociation between high- and low-frequency oscillations in relation to proposals that lower-frequency oscillations are generated by feedback pathways within visual cortex. PMID- 22305752 TI - Drosophila Pez acts in Hippo signaling to restrict intestinal stem cell proliferation. AB - The conserved Hippo signaling pathway acts in growth control and is fundamental to animal development and oncogenesis. Hippo signaling has also been implicated in adult midgut homeostasis in Drosophila. Regulated divisions of intestinal stem cells (ISCs), giving rise to an ISC and an enteroblast (EB) that differentiates into an enterocyte (EC) or an enteroendocrine (EE) cell, enable rapid tissue turnover in response to intestinal stress. The damage-related increase in ISC proliferation requires deactivation of the Hippo pathway and consequential activation of the transcriptional coactivator Yorkie (Yki) in both ECs and ISCs. Here, we identify Pez, an evolutionarily conserved FERM domain protein containing a protein tyrosine phosphatase (PTP) domain, as a novel binding partner of the upstream Hippo signaling component Kibra. Pez function--but not its PTP domain- is essential for Hippo pathway activity specifically in the fly midgut epithelium. Thus, Pez displays a tissue-specific requirement and functions as a negative upstream regulator of Yki in the regulation of ISC proliferation. PMID- 22305753 TI - Functional biases in visual cortex neurons with identified projections to higher cortical targets. AB - BACKGROUND: Visual perception involves information flow from lower- to higher order cortical areas, which are known to process different kinds of information. How does this functional specialization arise? As a step toward addressing this question, we combined fluorescent retrograde tracing with in vivo two-photon calcium imaging to simultaneously compare the tuning properties of neighboring neurons in areas 17 and 18 of ferret visual cortex that have different higher cortical projection targets. RESULTS: Neurons projecting to the posterior suprasylvian sulcus (PSS) were more direction selective and preferred shorter stimuli, higher spatial frequencies, and higher temporal frequencies than neurons projecting to area 21, anticipating key differences between the functional properties of the target areas themselves. These differences could not be explained by a correspondence between anatomical and functional clustering within early visual cortex, and the largest differences were in properties generated within early visual cortex (direction selectivity and length preference) rather than in properties present in its retinogeniculate inputs. CONCLUSIONS: These projection cell groups, and hence the higher-order visual areas to which they project, likely obtain their functional properties not from biased retinogeniculate inputs but from highly specific circuitry within the cortex. PMID- 22305754 TI - Loom-sensitive neurons link computation to action in the Drosophila visual system. AB - BACKGROUND: Many animals extract specific cues from rich visual scenes to guide appropriate behaviors. Such cues include visual motion signals produced both by self-movement and by moving objects in the environment. The complexity of these signals requires neural circuits to link particular patterns of motion to specific behavioral responses. RESULTS: Through electrophysiological recordings, we characterize genetically identified neurons in the optic lobe of Drosophila that are specifically tuned to detect motion signals produced by looming objects on a collision course with the fly. Using a genetic manipulation to specifically silence these neurons, we demonstrate that signals from these cells are important for flies to efficiently initiate the loom escape response. Moreover, through targeted expression of channelrhodopsin in these cells, in flies that are blind, we reveal that optogenetic stimulation of these neurons is typically sufficient to elicit escape, even in the absence of any visual stimulus. CONCLUSIONS: In this compact nervous system, a small group of neurons that extract a specific visual cue from local motion inputs serve to trigger the ethologically appropriate behavioral response. PMID- 22305755 TI - Driving oscillatory activity in the human cortex enhances motor performance. AB - Voluntary movement is accompanied by changes in the degree to which neurons in the brain synchronize their activity within discrete frequency ranges. Two patterns of movement-related oscillatory activity stand out in human cortical motor areas. Activity in the beta frequency (15-30 Hz) band is prominent during tonic contractions but is attenuated prior to and during voluntary movement. Without such attenuation, movement may be slowed, leading to the suggestion that beta activity promotes postural and tonic contraction, possibly at a cost to the generation of new movements. In contrast, activity in the gamma (60-90 Hz) band increases during movement. The direction of change suggests that gamma activity might facilitate motor processing. In correspondence with this, increased frontal gamma activity is related with reduced reaction times. Yet the possibility remains that these functional correlations reflect an epiphenomenal rather than causal relationship. Here we provide strong evidence that oscillatory activities at the cortical level are mechanistically involved in determining motor behavior and can even improve performance. By driving cortical oscillations using noninvasive electrical stimulation, we show opposing effects at beta and gamma frequencies and interactions with motor task that reveal the potential quantitative importance of oscillations in motor behavior. PMID- 22305756 TI - Myosin-IXA regulates collective epithelial cell migration by targeting RhoGAP activity to cell-cell junctions. AB - BACKGROUND: Epithelial tissues undergo extensive collective movements during morphogenesis, repair, and renewal. Collective epithelial cell migration requires the intercellular coordination of cell-cell adhesions and the establishment of anterior-posterior polarity, while maintaining apical-basal polarity, but how this is achieved at the molecular level is not well understood. RESULTS: Using an RNA interference-based screen to identify Rho family GTPase regulators required for the collective migration of human bronchial epithelial cells, we identified myosin-IXA (gene name: Myo9a). Depletion of myosin-IXA, a RhoGAP and actin motor protein, in collectively migrating cells led to altered organization of the actin cytoskeleton and tension-dependent disruption of cell-cell adhesions, followed by an inability to form new adhesions resulting in cell scattering. Closer examination revealed that myosin-IXA is required during the formation of junction associated actin bundles soon after cell-cell contact. Structure-function analysis of myosin-IXA revealed that the motor domain is necessary and sufficient for binding to actin filaments, whereas expression of the RhoGAP domain partially rescued the cell scattering phenotype induced by myosin-IXA depletion. Finally, a fluorescence resonance energy transfer biosensor revealed a significant increase in Rho activity at nascent cell-cell contacts in myosin-IXA depleted cells compared to controls. CONCLUSION: We propose that myosin-IXA locally regulates Rho and the assembly of thin actin bundles associated with nascent cell-cell adhesions and that this is required to sustain the collective migration of epithelial cells. PMID- 22305757 TI - The motivations and experiences of living kidney donors: a thematic synthesis. AB - BACKGROUND: Living kidney donation is associated with better recipient outcomes compared with deceased kidney donation, but living kidney donors face the risk of physical and psychological complications. The aim of this study was to synthesize published qualitative studies of the experiences and perspectives of living kidney donors. METHODS: We conducted a systematic review and thematic synthesis of qualitative studies of motivations to donate and experiences after donation of living kidney donors. MEDLINE, Embase, PsycINFO, CINAHL, and reference lists of articles were searched to April 2011. RESULTS: 26 studies involving 478 donors were included. We identified 6 themes about the decision to donate: compelled altruism, inherent responsibility, accepting risks, family expectation, personal benefit, and spiritual confirmation. Three themes dominated the impact of donation and postdonation: renegotiating identity (including subthemes of fear and vulnerability, sense of loss, depression and guilt, new appreciation of life, and personal growth and self-worth), renegotiating roles (including subthemes of multiplicity of roles, unable to resume previous activities, and hero status), and renegotiating relationships (including subthemes of neglect, proprietorial concern, strengthened family and recipient bonds, and avoidance of recipient indebtedness). CONCLUSIONS: Kidney donation has a profound and multifaceted impact on the lives of donors and requires them to renegotiate their identity, roles, and relationships. Strategies to safeguard against unwarranted coercion, and to maximize donor resilience, capacity to negotiate their multiple roles as a patient and carer, emotional fortitude, and ability to have balanced expectations and relationships with the recipient and the family are needed to ultimately protect the safety and well-being of living kidney donors. PMID- 22305758 TI - Novel markers of kidney function as predictors of ESRD, cardiovascular disease, and mortality in the general population. AB - BACKGROUND: Cystatin C level predicts mortality more strongly than serum creatinine level. It is unknown whether this advantage extends to other outcomes, such as kidney failure, or whether other novel renal filtration markers share this advantage in predicting outcomes. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: 9,988 participants in the Atherosclerosis Risk in Communities (ARIC) Study, a population-based study in 4 US communities, followed for approximately 10 years. PREDICTORS: Serum creatinine-based estimated glomerular filtration rate calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (eGFR(CKD-EPI)) and cystatin C, beta-trace protein (BTP), and beta(2)-microglobulin (B2M) levels. OUTCOMES: Mortality, coronary heart disease, heart failure, and kidney failure. RESULTS: Higher cystatin C and B2M concentrations were associated more strongly with mortality (n = 1,425) than BTP level and all were associated more strongly than eGFR(CKD-EPI) (adjusted HR for the upper 6.7 percentile compared with the lowest quintile: 1.6 [95% CI, 1.3-1.9] for eGFR(CKD-EPI), 2.9 [95% CI, 2.3-3.6] for cystatin C level, 1.9 [95% CI, 1.5-2.4] for BTP level, and 3.0 [95% CI, 2.4-3.8] for B2M level). Similar patterns were observed for coronary heart disease (n = 1,279), heart failure (n = 803), and kidney failure (n = 130). The addition of cystatin C, BTP, and B2M levels to models including eGFR(CKD-EPI) and all covariates, including urinary albumin-creatinine ratio, significantly improved risk prediction for all outcomes (P < 0.001). LIMITATIONS: No direct measurement of GFR. CONCLUSIONS: B2M and, to a lesser extent, BTP levels share cystatin C's advantage over eGFR(CKD-EPI) in predicting outcomes, including kidney failure. These additional markers may be helpful in improving estimation of risk associated with decreased kidney function beyond current estimates based on eGFR(CKD-EPI). PMID- 22305759 TI - Age and the associations of living donor and expanded criteria donor kidneys with kidney transplant outcomes. AB - BACKGROUND: Recent studies show a survival advantage with kidney transplant in elderly patients compared with those on dialysis therapy. STUDY DESIGN: In our present study, we examined and compared the association of expanded criteria donor (ECD) kidney and living kidney donation with the outcome of kidney transplant across different ages, including elderly recipients. SETTING & PARTICIPANTS: Using the Scientific Registry of Transplant Recipients, we identified 145,470 adult kidney transplant patients. Mortality and death-censored transplant failure risks were estimated by Cox proportional regression analyses during follow-up with a median of 3.9 years. PREDICTORS: ECD kidney and living kidney donation and age compared with others. OUTCOMES: Mortality and death censored transplant failure risk. RESULTS: Patients were aged 45 +/- 16 years and included 40% women and 19% patients with diabetes. Compared with transplant recipients 55 to younger than 65 years, the fully adjusted death-censored transplant failure risk was higher in patients 75 years and older (HR, 1.30; 95% CI, 1.09-1.56), 35 to younger than 55 years (HR, 1.13; 95% CI, 1.08-1.17), and 18 to younger than 35 years (HR, 1.64; 95% CI, 1.57-1.71). Compared with non-ECD kidneys, ECD kidneys were significant predictors of mortality in nonelderly patients (18-<35 years: HR, 1.46 [95% CI, 1.19-1.77]; 35-<55 years: HR, 1.23 [95% CI, 1.14-1.32]; and 55-<65 years: HR, 1.26 [95% CI, 1.15-1.38]) and patients 65 to younger than 70 years (HR, 1.20; 95% CI, 1.05-1.36), but not in other groups of elderly patients (HRs of 1.12 [95% CI, 0.93-1.36] for 70-<75 years and 1.04 [95% CI, 0.74-1.47] for >=75 years). Similar results were found for risk of transplant loss. Compared with deceased donor kidneys, a living donor kidney was associated with better survival in all age groups and lower transplant loss risk in patients younger than 70 years. LIMITATIONS: Unmeasured confounders cannot be adjusted for. CONCLUSIONS: For deceased donors, ECD kidneys are not associated with increased mortality or transplant failure in recipients older than 70 years. For all types of donors, the persistent association between living donor kidneys and lower all-cause mortality across all ages suggests that, if possible, elderly patients gain longevity from living donor kidney transplant. PMID- 22305760 TI - Trajectories of kidney function decline in the 2 years before initiation of long term dialysis. AB - BACKGROUND: Little is known about patterns of kidney function decline leading up to the initiation of long-term dialysis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 5,606 Veterans Affairs patients who initiated long term dialysis in 2001-2003. PREDICTOR: Trajectory of estimated glomerular filtration rate (eGFR) during the 2-year period before initiation of long-term dialysis. OUTCOMES & MEASUREMENTS: Patient characteristics and care practices before and at the time of dialysis initiation and survival after initiation. RESULTS: We identified 4 distinct trajectories of eGFR during the 2-year period before dialysis initiation: 62.8% of patients had persistently low level of eGFR < 30 mL/min/1.73 m2 (mean eGFR slope, 7.7 +/- 4.7 [SD] mL/min/1.73 m2 per year), 24.6% had progressive loss of eGFR from levels of approximately 30-59 ml/min/1.73 m2 (mean eGFR slope, 16.3 +/- 7.6 mL/min/1.73 m2 per year), 9.5% had accelerated loss of eGFR from levels > 60 mL/min/1.73 m2 (mean eGFR slope, 32.3 +/- 13.4 mL/min/1.73 m2 per year), and 3.1% experienced catastrophic loss of eGFR from levels > 60 mL/min/1.73 m2 within 6 months or less. Patients with steeper eGFR trajectories were more likely to have been hospitalized and have an inpatient diagnosis of acute kidney injury. They were less likely to have received recommended predialysis care and had a higher risk of death in the first year after dialysis initiation. CONCLUSIONS: There is substantial heterogeneity in patterns of kidney function loss leading up to the initiation of long-term dialysis perhaps calling for a more flexible approach toward preparing for end stage renal disease. PMID- 22305761 TI - Para-meatus skin incision with long channel technique for midshaft hypospadias repair without penile curvature. AB - OBJECTIVE: To report a new surgical technique for midshaft hypospadias repair without penile curvature. METHODS: From September 2007 to October 2010, 21 patients, aged 13 months to 8.9 years, underwent single-stage hypospadias repair by 1 surgeon. The skin incision was created around the meatus, and a long channel beneath the urethral plate was created through the incision to the apex of the glans. The inner preputial flaps were tubularized into a neourethra, which was then transposed to the ventral channel through a ventrolateral tunnel beneath Buck's fascia. Most of the neourethra was covered by the intact soft tissue of the distal ventral penis. The proximal portion of the neourethra was covered by Buck's and dartos fascia around the skin incision, and the skin incision was closed longitudinally. The length of the urethral defect and channel and the postoperative complications were collected and analyzed. RESULTS: A total of 21 patients underwent single-staged hypospadias repair. The average length of the channel was 30 mm (range 25-35). The average length of the neourethra was 35 mm (range 30 to 40). The mean operative time was 60 minutes (range 50-70). The mean hospital stay was 12 days (range 10-14). With an average follow-up of 20 months (range 6-37), no postoperative complication was detected. CONCLUSION: This technique provides excellent short-term results for midshaft hypospadias without penile curvature and is a safe and simple solution. PMID- 22305762 TI - Non-contrast computed tomography after percutaneous nephrolithotomy: findings and clinical significance. AB - OBJECTIVE: To describe the post-percutaneous nephrolithotomy (PNL) non-contrast enhanced computed tomography (NCCT) findings and assessed their clinical significance. NCCT evaluates stone clearance after PNL and also reveals procedure related changes. METHODS: One hundred consecutive patients who underwent PNL were evaluated by NCCT one day post-procedure. Two radiologists analyzed the type and severity of the NCCT findings, which were then statistically analyzed in relation to the patient's clinical course. RESULTS: The patients' mean age was 54 years (range 18-82) and the mean maximal stone diameter was 37 mm (range 15-70). The median operative time was 110 minutes for an immediate stone-free rate of 83%, changing to 94% (P = .073) after a second-look PNL in 11 patients. The post-PNL NCCT findings were hydronephrosis (70%), atelectasis (54%), ipsilateral pleural effusion (52%), paracolic gutter fluid (44%), perinephric hematoma (40%), perinephric fluid (32%), ureteronephrosis (31%), renal swelling (23%), contralateral pleural effusion (22%), residual fragments (RFs) (17%), subcapsular hematoma (10%), and flank hematoma (6%). Univariate analysis revealed a significant association with clinical variables for all NCCT findings except for atelectasis, ureteronephrosis, contralateral pleural effusion, RFs, and flank hematoma. In multivariate analysis, only perinephric fluid (P = .007) and ipsilateral pleural effusion (P = .034) were associated with longer hospitalization, and perinephric fluid with longer recovery (P = .004). The complication rate was 12%, but none were linked with the radiological findings. CONCLUSION: This work describes the post-PNL NCCT findings and their clinical significance. Perinephric fluid and ipsilateral pleural effusion were found to independently predict longer hospitalization and recovery time. PMID- 22305763 TI - Long-term outcomes after primary failures of artificial urinary sphincter implantation. AB - OBJECTIVES: To assess our institutional outcomes after primary artificial urinary sphincter (AUS) failures. METHODS: From 1985 to 2010, a total of 149 patients underwent 318 primary and additional AUS procedures. We classified additional procedures as revisions, replacements, or explantations. RESULTS: At a median of 52 months (range, 6-250 months), 53% of patients had required at least 1 additional procedure beyond their initial implantation. These included 106 (63%) revisions, 42 (24.9%) explantations, and 21 (12.4%) replacements. The most common revision was reservoir upsizing (37/106). Reasons for first revision included recurrent incontinence (56.7%), mechanical malfunction (22%), and infection or erosion (18.6%). Explantations were performed primarily for infection and erosion (64.3%). Median time to first revision was 20.1 months (range, 0.1-173 months) after implantation, with a median of 9.5 months (range, 1-102 months) between revisions. Explantation occurred at a median of 22 months (range, 1-221 months) after implant, and subsequent replacement at a median of 33.6 months (range, 2 138 months). At 5 years, 28/83 (33.7%) patients had undergone no additional procedures. Patients with previous radiation were more likely to experience infection (P = .03; OR 3.99; 95% CI 1.03-15.42). Patients with previous myocardial infarction were more likely to experience erosion (P = .04; OR 2.29; 95% CI 1.05-5.02), and obese patients were more likely to experience mechanical malfunction (P = .04; OR 2.62; 95% CI 1.07-6.4). CONCLUSIONS: More than half of patients with an AUS will require additional procedures, most likely revision. Radiation, previous myocardial infarction, and obesity are linked to complications. Median time to first revision or explantation is slightly less than 2 years, indicating that long-term follow-up is required after initial implantation. PMID- 22305764 TI - The implications of PIP are more than just cosmetic. PMID- 22305765 TI - Evidence supports the obvious: suicides need not happen. PMID- 22305766 TI - Depression in adolescence. AB - Unipolar depressive disorder in adolescence is common worldwide but often unrecognised. The incidence, notably in girls, rises sharply after puberty and, by the end of adolescence, the 1 year prevalence rate exceeds 4%. The burden is highest in low-income and middle-income countries. Depression is associated with substantial present and future morbidity, and heightens suicide risk. The strongest risk factors for depression in adolescents are a family history of depression and exposure to psychosocial stress. Inherited risks, developmental factors, sex hormones, and psychosocial adversity interact to increase risk through hormonal factors and associated perturbed neural pathways. Although many similarities between depression in adolescence and depression in adulthood exist, in adolescents the use of antidepressants is of concern and opinions about clinical management are divided. Effective treatments are available, but choices are dependent on depression severity and available resources. Prevention strategies targeted at high-risk groups are promising. PMID- 22305767 TI - Implementation of mental health service recommendations in England and Wales and suicide rates, 1997-2006: a cross-sectional and before-and-after observational study. AB - BACKGROUND: Research investigating which aspects of mental health service provision are most effective in prevention of suicide is scarce. We aimed to examine the uptake of key mental health service recommendations over time and to investigate the association between their implementation and suicide rates. METHODS: We did a descriptive, cross-sectional, and before-and-after analysis of national suicide data in England and Wales. We collected data for individuals who died by suicide between 1997 and 2006 who were in contact with mental health services in the 12 months before death. Data were obtained as part of the National Confidential Inquiry into Suicide and Homicide by People with Mental Illness. When denominator data were missing, we used information from the Mental Health Minimum Data Set. We compared suicide rates for services implementing most of the recommendations with those implementing fewer recommendations and examined rates before and after implementation. We stratified results for level of socioeconomic deprivation and size of service provider. FINDINGS: The average number of recommendations implemented increased from 0.3 per service in 1998 to 7.2 in 2006. Implementation of recommendations was associated with lower suicide rates in both cross-sectional and before-and-after analyses. The provision of 24 h crisis care was associated with the biggest fall in suicide rates: from 11.44 per 10 000 patient contacts per year (95% CI 11.12-11.77) before to 9.32 (8.99 9.67) after (p<0.0001). Local policies on patients with dual diagnosis (10.55; 10.23-10.89 before vs 9.61; 9.18-10.05 after, p=0.0007) and multidisciplinary review after suicide (11.59; 11.31-11.88 before vs 10.48; 10.13-10.84 after, p<0.0001) were also associated with falling rates. Services that did not implement recommendations had little reduction in suicide. The biggest falls in suicide seemed to be in services with the most deprived catchment areas (incidence rate ratio 0.90; 95% CI 0.88-0.92) and the most patients (0.86; 0.84 0.88). INTERPRETATION: Our findings suggest that aspects of provision of mental health services can affect suicide rates in clinical populations. Investigation of the relation between new initiatives and suicide could help to inform future suicide prevention efforts and improve safety for patients receiving mental health care. FUNDING: National Patient Safety Agency, UK. PMID- 22305768 TI - Emerging roles of the neuronal nucleolus. AB - Although, the nucleolus has been observed for almost 200 years in neurons, studies that directly address the neuronal roles of this subnuclear structure have appeared only recently. The aim of this review is to discuss recent progress and identify some critical questions that remain to be answered. As expected for the cellular center of ribosome biogenesis, the nucleolus is essential for the growth of developing neurons, including neurite morphogenesis and long-term maintenance of mature neurons. In addition, the nucleolus contributes to neuronal stress responses, including the regulation of apoptosis. Hence, disrupted neurodevelopment or neurodegeneration are among the likely consequences of nucleolar dysfunction. Conversely, the presence of active nucleoli may determine the potential for neurorepair. PMID- 22305770 TI - SmartStretchTM technology. II. Improving the tenderness of leg meat from sheep using a meat stretching device. AB - This study evaluated the effect of stretching hot-boned sheep hindlegs from 40 sheep carcases, classified as mutton, using a prototype device (SmartStretchTM). Left and right legs were collected pre-rigor and randomly allocated to one of four treatments; 0days ageing+SmartStretchTM, 0days ageing+no stretch, 5days ageing+SmartStretchTM and 5days ageing+no stretch. There was a significant interaction between stretch treatment and ageing (P<0.05) for shear force of the m. biceps femoris such that stretched and aged samples were the most tender. By contrast stretched m. semimembranosus (SM) had a significantly (P<0.05) lower shear force only at 0days of ageing. Stretching produced longer sarcomeres (P<0.001) for both the SM and m. semitendinosus muscles. Myofibrillar degradation indicated by particle size analysis or histology was not affected by stretching, but there was an ageing effect (P<0.001). SmartStretchTM provided significant improvements in tenderness of the individual muscles. PMID- 22305769 TI - Rodent models for HIV-associated neurocognitive disorders. AB - Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) reflect the spectrum of neural impairments seen during chronic viral infection. Current research efforts focus on improving antiretroviral and adjunctive therapies, defining disease onset and progression, facilitating drug delivery, and halting neurodegeneration and viral resistance. Because HIV is species specific, generating disease in small-animal models has proved challenging. After two decades of research, rodent HAND models now include those containing a human immune system. Antiviral responses, neuroinflammation and immunocyte blood-brain barrier (BBB) trafficking follow HIV infection in these rodent models. We review these and other rodent models of HAND and discuss their unmet potential in reflecting human pathobiology and in facilitating disease monitoring and therapeutic discoveries. PMID- 22305771 TI - Triplex Doppler evaluation of uterine arteries in cyclic and pregnant domestic cats. AB - The aims were to determine resistance index (RI) and pulsatility index (PI) in the uterine arteries of cyclic and pregnant domestic cats comparing the left and right uterine horns, as well as the majority or minority uterine horns, based on fetus number per horn; to determine the presence or absence of an early diastolic notch (EDN) in the uterine artery of pregnant queens. Ten domestic cats were followed during one cycle and one pregnancy until 63rd days after mating. The estrous cycle length was 16 +/- 9.57 days. The uterine horn with the highest number of fetuses (majority uterine horn - MUH) presented 2.0 +/- 1.0 fetus and the lower (minority uterine horn - miUH) presentes 0.78 +/- 0.67 fetus. There were no differences in indexes between uterine arteries during the cycles and pregnancies. The RI and PI of MUH were lower than miUH (P<0.05). Uterine artery of the MUH presented lower indexes than miUH during the acceptance period (P<0.05). On D14 of pregnancy, uterine artery presented reductions in both indexes for the miUH. On D56, the PI was reduced in the miUH. The indexes depended on the week of pregnancy. EDN was present on the uterine arteries of all cats until D35, but disappeared by D49. The blood flow varied according to the category of horn. PMID- 22305772 TI - Listener effort for highly intelligible tracheoesophageal speech. AB - The purpose of this study was to determine whether: (a) inexperienced listeners can reliably judge listener effort and (b) whether listener effort provides unique information beyond speech intelligibility or acceptability in tracheoesophageal speech. Twenty inexperienced listeners made judgments of speech acceptability and amount of effort required to listen to 14 male tracheoesophageal speakers using a paired comparison paradigm. Intelligibility was controlled to limit the analysis to the relationship between ratings of listener effort and speech acceptability. Results showed that as a group, inexperienced listeners reliably rated both speech acceptability and listener effort. In addition, ratings of speech acceptability and listener effort were strongly correlated (r>.99); however, there was evidence that some individual listeners assigned different ratings for each dimension for the same speech samples. Results have important implications for communication success for tracheoesophageal speakers. LEARNING OUTCOMES: Readers will be able to describe: (a) the measurement of listener burden in speech and (b) the differences and relationships among listener effort, speech acceptability and speech intelligibility. PMID- 22305773 TI - "One-stop-shop" cardiac MRI at 3.0T for the detection of coronary artery disease. PMID- 22305774 TI - A hypertensive patient presenting with paraneoplastic perimyocarditis and myositis due to pheochromocytoma. PMID- 22305775 TI - Metabolic syndrome and renal disease. AB - The metabolic syndrome (MetS) is a cluster of risk factors including insulin resistance, dyslipidemia and hypertension which are also relevant for the development of chronic kidney disease (CKD). It has proven difficult to elucidate whether the renal dysfunction in MetS is due to the MetS itself or the individual risk factors. For example, obesity - which is also part of the MetS - may enhance the risk of renal dysfunction development probably through mechanisms associated with renal hyperfiltration, hyperperfusion and focal glomerulosclerosis. Insulin resistance also promotes kidney disease by worsening renal hemodynamics. In patients with MetS, tubular atrophy, interstitial fibrosis, and arteriolar sclerosis indicating the presence of vascular damage, have also been described. As yet, there has been little evidence that preventing or treating symptoms of the MetS protects patients from renal impairment. PMID- 22305776 TI - Determinants of cardiovascular mortality in a cohort of primary care patients with chronic ischemic heart disease. BARBANZA Ischemic Heart Disease (BARIHD) study. AB - BACKGROUND: Prognosis of chronic patients with established ischemic heart disease (IHD) is not fully understood. The objective was to determine which factors are related to cardiovascular death and hospitalizations in patients with IHD within a primary care network. MATERIALS AND METHODS: A cohort study was carried out by 69 primary care providers in Spain in 2007. Participants were followed up for a mean of 2.2 +/- 0.3 years. 1095 patients were recruited if they had established (at least 1 year of known disease) IHD (myocardial infarction or and stable or unstable angina). Several hypothesized determinants of cardiovascular mortality were studied, using Cox proportional hazard regression models. Subgroup analysis was also performed for participants without cardiovascular admissions within the last year. RESULTS: Mean time since first IHD diagnosis was 7.6 +/- 6.0 years. Annual all-cause mortality rate was 3.25%, with 44 cardiovascular deaths and 119 cardiovascular admissions. The main prognostic factor for cardiovascular death was previous heart failure (hazard ratio [HR] 4.32, 95% confidence interval [CI] 2.30 to 8.11, p<0.001). Recent cardiovascular admission doubled the risk for death (HR 2.01, CI 1.06 to 3.81, p=0.031). Results showed that use of beta blockers and increased physical activity were the main protective factors. Patients without a recent cardiovascular admission showed previous heart failure as the main significant factor for cardiovascular death. CONCLUSIONS: Patients with chronic IHD in a primary care setting may need a closer follow-up in the presence of previous conditions such as heart failure. Physical activity and treatment with beta blockers were the factors giving these patients the greatest protection. PMID- 22305777 TI - Post retentive ability of a new resin composite with low stress behaviour. AB - OBJECTIVES: To assess by means of push-out test the post retentive potential of a new flowable resin composite with low polymerization stress. METHODS: SureFil((r)) SDRTM (Dentsply, S) was compared with the resin cement Calibra (Dentsply, C). S and C were used in combination with the adhesive XP Bond (Dentsply, XPB). In C group the Self-Cure Activator was mixed with XPB. The following types of fibre posts were luted into 30 extracted premolars: Radix Fiber Post (Dentsply, R), DT Light Post (RTD, LP), ER Dentin Post (Komet, ER), DT Light SL (VDW, SL), FibreKleer (Jeneric Pentron, F). Six posted roots per group were tested. Each root provided three to five 1mm-thick slices. Measured push-out strengths were differentiated by post space level and statistically analysed (p<0.05). The failure mode of each debonded specimen was assessed. RESULTS: Cement type did not have a significant effect on post retention (p=0.54). Post type was a significant factor for push-out strength (p<0.001). LP exhibited significantly higher retentive strength than SL and F; push-out strengths of ER and R were significantly higher than those of F. Post retention was significantly influenced by post space level (p<0.001). Significantly higher push-out strengths were recorded at the coronal third than at the middle and apical levels. The post cement interaction was significant (p=0.002). Posts luted with S most often failed at the cement-post interface. CONCLUSIONS: When the new flowable low stress composite was used to lute fibre posts, similar retentive strengths to those of a marketed cement from the same manufacturer were achieved. CLINICAL SIGNIFICANCE: SureFil((r)) SDRTM, a flowable composite originally proposed for bulk filling of posterior restorations, exhibited post retentive strengths similar to those of a cement by the same manufacturer. With a relatively high filler load, yet a low curing stress, SureFil((r)) SDRTM may be adequate for both post cementation and core build-up. PMID- 22305778 TI - Chlorhexidine delivery system from titanium/polybenzyl acrylate coating: evaluation of cytotoxicity and early bacterial adhesion. AB - OBJECTIVES: The formation of biofilms on titanium dental implants is one of the main causes of failure of these devices. Streptococci are considered early colonizers that alter local environment favouring growing conditions for other colonizers. Chlorhexidine (CHX) is so far the most effective antimicrobial treatment against a wide variety of Gram-positive and Gram-negative organisms as well as fungi. This study was designed to develop a CHX delivery system appropriate for healing caps and abutments, with suitable drug release rate, effective as antimicrobial agent, and free of cytotoxic effects. METHODS: Polybenzyl acrylate (PBA) coatings with and without CHX (Ti/PBA and Ti/PBA-CHX, respectively) and different drug loads (0.35, 0.70, and 1.40%, w/w) were assayed. The cytotoxic effect of CHX released from the different substrates on UMR106 cells was tested by alkaline phosphatase specific activity (ALP), and microscopic evaluation of the cells. Non-cytotoxic drug load (0.35%, w/w) was selected to evaluate the antimicrobial effectiveness of the system using a microbial consortium of Streptococcus species. RESULTS: The kinetic profile of CHX delivered by Ti/PBA-CHX showed an initial fast release rate followed by a monotonic increase of delivered mass over 48 h. The number of attached bacteria decreased in the following order: Ti>Ti/PBA>Ti/PBA-0.35. CONCLUSIONS: PBA-0.35 coating is effective to inhibit the adhesion of early colonizers on Ti without any cytotoxic effect on UMR-106 cells. PMID- 22305779 TI - Cytochalasin D, a tropical fungal metabolite, inhibits CT26 tumor growth and angiogenesis. AB - OBJECTIVE: To investigate whether cytochalasin D can induce antitumor activities in a tumor model. METHODS: Murine CT26 colorectal carcinoma cells were cultured in vitro and cytochalasin D was used as a cytotoxic agent to detect its capabilities of inhibiting CT26 cell proliferation and inducing cell apoptosis by MTT and a TUNEL-based apoptosis assay. Murine CT26 tumor model was established to observe the tumor growth and survival time. Tumor tissues were used to detect the microvessel density by immunohistochemistry. In addition, alginate encapsulated tumor cell assay was used to quantify the tumor angiogenesis in vivo. RESULTS: Cytochalasin D inhibited CT26 tumor cell proliferation in time and dose dependent manner and induced significant CT26 cell apoptosis, which almost reached the level induced by the positive control nuclease. The optimum effective dose of cytochalasin D for in vivo therapy was about 50 mg/kg. Cytochalasin D in vivo treatment significantly inhibited tumor growth and prolonged the survival times in CT26 tumor-bearing mice. The results of immunohistochemistry analysis and alginate encapsulation assay indicated that the cytochalasin D could effectively inhibited tumor angiogenesis. CONCLUSIONS: Cytochalasin D inhibits CT26 tumor growth potentially through inhibition of cell proliferation, induction of cell apoptosis and suppression of tumor angiogenesis. PMID- 22305780 TI - Antidiabetic activity of aqueous root extract of Merremia tridentata (L.) Hall. f. in streptozotocin-induced-diabetic rats. AB - OBJECTIVE: To investigate the antidiabetic effect of aqueous extract of Merremia tridentata (M. tridentata) root (MTRAE) in normal, glucose-loaded hyperglycemic and streptozotocin (STZ)-induced diabetic rats. METHODS: Oral administration of MTRAE at the doses of 50, 100 and 150 mg/kg was studied in normal, glucose-loaded and STZ-diabetic rats. The three doses caused significant reduction in blood glucose levels in all the models. RESULTS: The effect was more pronounced in 100 and 150 mg/kg than 50 mg/kg. MTRAE also showed significant increase in serum insulin, body weight and glycogen content in liver and skeletal muscle of STZ induced diabetic rats while there was significant reduction in the levels of serum triglyceride and total cholesterol. MTRAE also showed significant antilipidperoxidative effect in the pancreas of STZ-induced diabetic rats. The antidiabetic effect of M. tridentata was compared with glibenclamide, a well known hypoglycemic drug. CONCLUSIONS: The results indicate that aqueous extract of M. tridentata root possesses significant antidiabetic activity. PMID- 22305781 TI - Bronchodilatory and mast cell stabilising activity of Cressa cretica L.: evaluation through in vivo and in vitro experimental models. AB - OBJECTIVE: To evaluate the effect of ethylacetate fraction (Fr-Et) and methanolic fraction (Fr-Me) obtained from Cressa cretica L.(C. cretica) L. on experimental models for bronchodilatory activity and mast cell stabilising activity. METHODS: The effect of Fr-Et and Fr-Me were studied on acetylcholine and histamine aerosol induced broncospasm using guinea pigs as experimental animals. Also, the effects of these fractions were evaluated on the isolated guinea pig tracheal preparations. Besides this mast cell degranulation effect was assessed using egg albumin and compound 48/80 on rat peritoneal mast cells. RESULTS: Significant increase in preconvulsion time was observed due to pretreatment with the fractions when guinea pigs were exposed to histamine and acetylcholine aerosol. Fr-Et and Fr-Me significantly increased the preconvulsion in a dose depended manner that suggestive of bronchodilating activity. Fr-Et and Fr-Me exhibited a significant concentration dependant relaxant effect on guinea pig trachea pre contracted with CCh, K(+) and histamine. The results revealed that Fr-Et to be more potent than Fr-Me in relaxing histamine and K(+) and calcium induced contraction than CCh induced contractions. Studies on the fractions in protecting mast cell degranulation, which were elicited by the egg albumin as well as synthetic compound 48/80 revealed both the fractions significantly protect the mast cell degranulation, which release mediators such as histamine and proinflammatory cytokines through various stimuli in a dose depended manner. CONCLUSIONS: Thus our study established the bronchodilator activity, and mast cell stabilizing activity which are important mediators that provoke or sustain in asthma. PMID- 22305782 TI - Effect of Buchanania lanzan Spreng. bark extract on cyclophosphamide induced genotoxicity and oxidative stress in mice. AB - OBJECTIVE: To elucidate the effect of ethanolic extract of Buchanania lanzan Spreng. (B. lanan) bark against cyclophosphamide induced genotoxicity and oxidative stress in mice. METHODS: The prevalence of micronuclei in bone marrow, the extent of lipid peroxidation, reduced glutathione and the status of the antioxidant enzymes, superoxide dismutase and catalase in liver of mice were used as intermediate biomarkers for chemoprotection. Lipid peroxidation and associated compromised antioxidant defenses in cyclophosphamide treated mice were observed in the liver. RESULTS: Pre-treatment with B. lanzan 250, 500 and 1,000 mg/kg, p.o., daily for 7 days significantly reduced the chromosomal damage and lipid peroxidation with concomitant changes in antioxidants and detoxification systems. CONCLUSIONS: These results point out the presence of chemopreventive phytoconstituents in the crude extract offering protection against cyclophosphamide induced genotoxicity and oxidative stress in mice. PMID- 22305783 TI - Antihyperglycemic effects of the methanol leaf extract of Diaphananthe bidens in normoglycemic and streptozotocin-induced hyperglycemic rats. AB - OBJECTIVE: To evaluate the methanol leaf extract of Diaphanathe bidens (D. bidens) (AFZEL. EX SW) SCHLTR for antihyperglycemic activity in order to confirm it antidiabetic potential. METHODS: D. bidens was extracted by cold maceration for 48 h and concentrated in vacuo to yield D. bidens extract (DBE). Hyperglycemia was induced by intraperitoneal administration of streptozotocin (75 mg/kg). Oral glucose tolerance test was done with 2 g/kg glucose load in normal rats. DBE (150, 300 and 600 mg/kg) was administered orally, while tolbutamide (100 mg/kg, p.o.) was used as the standard reference drug. Blood glucose levels determined using ACCUCHEK glucose auto-analyzer. The acute toxicity and phytochemical studies were also carried out. RESULTS: DBE (600 mg/kg) and tolbutamide (100 mg/kg) significantly (P<0.05, 0.005) reduced blood glucose levels of rats between 120 and 480 min post administration in normal rats. In the streptozotocin- induced hyperglycemic rats, DBE (150, 300, 600 mg/kg) caused significant (P<0.001) dose- and time- dependent reduction in the blood glucose levels by 1.7%, 22.8% and 43.4%, respectively at 480 min compared to the negative control group. DBE (600 mg/kg) reduced the blood glucose level of rats by 1.2% in the oral glucose tolerance test when compared with the normal saline treated group. The acute toxicity test showed that DBE was safe at the doses used and the phytochemical screening revealed the presence of saponins, steroids, tannins and terpernoids. CONCLUSIONS: D. bidens extract possess antihyperglycemic activity which may be mediated through pancreatic and extra-pancreatic pathways, thereby justifying it folkloric use. PMID- 22305784 TI - Gastroprotective effect of Achyranthes aspera Linn. leaf on rats. AB - OBJECTIVE: The study was aimed at evaluating the antiulcer activity of ethanolic extract of Achyranthes aspera (EEAA) leaf. METHODS: The anti-ulcer assays were performed on pylorus ligation and chronic ethanol induced ulcer model. The effects of the EEAA on gastric content volume, pH, free acidity, total acidity and ulcer index were evaluated. RESULTS: The percentage of ulcer protection (59.55% and 35.58%) was significantly (P < 0.001) higher in the groups treated with the high dose of EEAA (600 mg/kg), it also reduced the volume of gastric juice and total acidity whereas, gastric pH was increased significantly. CONCLUSIONS: The results of this study show significant gastroprotective activity of EEAA may be due to presence of phyto-constituents like flavanoids, saponins and tannins. PMID- 22305785 TI - Antimicrobial activity and essential oils of Curcuma aeruginosa, Curcuma mangga, and Zingiber cassumunar from Malaysia. AB - OBJECTIVE: To analyze the chemical composition of the essential oils of Curcuma aeruginosa (C. aeruginosa), Curcuma mangga (C. mangga), and Zingiber cassumunar (Z. cassumunar), and study their antimicrobial activity. METHODS: Essential oils obtained by steam distillation were analyzed by gas chromatography-mass spectrometry (GC-MS). The antimicrobial activity of the essential oils was evaluated against four bacteria: Bacillus cereus (B. cereus), Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa); and two fungi: Candida albicans (C. albicans) and Cyptococcus neoformans (C. neoformans), using disc-diffusion and broth microdilution methods. RESULTS: Cycloisolongifolene, 8,9-dehydro formyl (35.29%) and dihydrocostunolide (22.51%) were the major compounds in C. aeruginosa oil; whereas caryophyllene oxide (18.71%) and caryophyllene (12.69%) were the major compounds in C. mangga oil; and 2,6,9,9-tetramethyl-2,6,10-cycloundecatrien-1-one (60.77%) and alpha caryophyllene (23.92%) were abundant in Z. cassumunar oil. The essential oils displayed varying degrees of antimicrobial activity against all tested microorganisms. C. mangga oil had the highest and most broad-spectrum activity by inhibiting all microorganisms tested, with C. neoformans being the most sensitive microorganism by having the lowest minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values of 0.1 MUL/mL. C. aeruginosa oil showed mild antimicrobial activity, whereas Z. cassumunar had very low or weak activity against the tested microorganisms. CONCLUSIONS: The preliminary results suggest promising antimicrobial properties of C. mangga and C. aeruginosa, which may be useful for food preservation, pharmaceutical treatment and natural therapies. PMID- 22305786 TI - In vitro biofilm formation by uropathogenic Escherichia coli and their antimicrobial susceptibility pattern. AB - OBJECTIVE: To detect in vitro biofilm formation of uropathogenic Escherichia coli (E. coli) (UPEC) strains isolated from urine specimens and also to determine their antimicrobial susceptibility pattern using 13 commonly used antibiotics. METHODS: The present study comprised of 166 urine specimens collected from tertiary care hospitals in and around Coimbatore, South India. All the specimens were subjected to gram staining, bacterial culture and the E. coli strains were screened for biofilm formation using Tube Method (TM), Congo Red Agar (CRA) and Tissue Culture Plate method (TCP) respectively. Subsequently, the antimicrobial susceptibility test was performed by Kirby Bauer-disk diffusion method for the biofilm and non-biofilm producing E. coli strains. RESULTS: Of the 100 (60.2 %) E. coli strains, 72 strains displayed a biofilm positive phenotype under the optimized conditions in the Tube Method and the strains were classified as highly positive (17, 23.6%), moderate positive (19, 26.3 %) and weakly positive (36, 50.0 %), similarly under the optimized conditions on Congo Red agar medium, biofilm positive phenotype strains were classified as highly positive (23, 23 %), moderate positive (37, 37 %) and weakly positive (40, 40%). While in TCP method, the biofilm positive phenotype strains were also classified as highly positive (6, 6 %), moderate positive (80, 80 %) and weakly positive (14, 14 %), it didn't not correlate well with the tube method for detecting biofilm formation in E. coli. The rates of antibiotic resistance of biofilm producing E. coli were found to be 100 % for chloramphenicol and amoxyclav (amoxicillin and clavulanic acid), 86% for gentamicin and cefotaxime, 84% for ceftazidime, 83% for cotrimoxazole and piperacillin/tazobactam, 75% for tetracycline and 70% for amikacin. CONCLUSIONS: This study reveals the prevalence and antimicrobial susceptibility pattern of biofilm and non-biofilm producing uropathogenic E. coli strains. PMID- 22305787 TI - Antiplasmodial and analgesic activities of Clausena anisata. AB - OBJECTIVE: Antiplasmodial and analgesic activities of the leaf extract and fractions of Clausena anisata (C. anisata) were evaluated for antimalarial and analgesic activities. METHODS: The crude leaf extract (39-117 mg/kg) and fractions (chloroform and acqeous; 78 mg/kg) of C. anisata were investigated for antiplasmodial activity against chloroquine-sensitive Plasmodium berghei (P. berghei) infections in mice using suppressive, prophylactic and curative models and analgesic activity against acetic acid, formalin and heat-induced pains. Artesunate, 5 mg/kg and pyrimethamine, 1.2 mg/kg were used as positive controls. Thin films made from tail blood of each mouse were used to assess the level of parasitaemia of the mice. RESULTS: The extract and its fractions dose-dependently reduced parasitaemia induced by chloroquine-sensitive P. berghei in prophylactic, suppressive and curative models in mice. These reductions were statistically significant (P<0.001). They also improved the mean survival time (MST) from 17 to 21 days relative to control (P<0.01 - 0.001). On chemically and thermally-induced pains, the extract inhibited acetic acid and formalin-induced inflammation as well as hot plate-induced pain in mice. These inhibitions were statistically significant (P<0.001) and in a dose-dependent fashion. CONCLUSIONS: The antiplasmodial and analgesic effects of this plant may in part be mediated through its chemical constituents and it can be concluded that the C. anisata possess significant antimalarial and analgesic properties. PMID- 22305788 TI - Enhancing chloramphenicol and trimethoprim in vitro activity by Ocimum sanctum Linn. (Lamiaceae) leaf extract against Salmonella enterica serovar Typhi. AB - OBJECTIVE: To evaluate the antibacterial activity of Ocimum sanctum (O. sanctum) leaf extract, alone, and in combination with chloramphenicol (C) and trimethoprim (Tm) against Salmonella enterica serovar Typhi (S. typhi). METHODS: The antibacterial activity of ethanolic extract of tulsi, O. sanctum, leaf (TLE; 500 MUg) for 23 S. typhi isolates was determined following agar diffusion. The C (30 MUg) and Tm (5 MUg) activity alone and in combination with TLE (250 MUg) was determined by disk diffusion. The zone diameter of inhibition (ZDI) for the agents was recorded, and growth inhibitory indices (GIIs) were calculated. RESULTS: The S. typhi isolates (n=23), which were resistant to both C (ZDI 6 mm) and Tm (ZDI 6 mm), had TLE (500 MUg) ZDIs 16-24 mm. The ZDIs of C and Tm were increased up to 15-21 mm and 17-23 mm, respectively, when TLE (250 MUg) was added to the C and Tm discs. The GIIs ranged 0.789-1.235 and 0.894-1.352, due to combined activity against S. typhi isolates, of C and TLE and Tm and TLE, respectively. CONCLUSIONS: The data suggest that TLE, in combination with C and Tm, had synergistic activity for S. typhi isolates, and hence O. sanctum is potential in combating S. typhi drug resistance, as well promising in the development of non-antibiotic drug for S. typhi infection. PMID- 22305789 TI - In-vitro cytotoxic activity of beta-Sitosterol triacontenate isolated from Capparis decidua (Forsk.) Edgew. AB - OBJECTIVE: To study the isolation and characterization of the constituent responsible for the cytotoxic activity of the ethanolic extract of stem of Capparis decidua (C. decidua). METHODS: The preliminary cytotoxic effect of isolated compound (beta-Sitosterol triacontenate) was investigated by MTT assay on A549 solid tumor cells. RESULTS: IC(50) value of the beta-Sitosterol triacontenate was found to be 1 MUM. The cytotoxic activity increased in a dose dependent manner in case of beta-Sitosterol triacontenate. CONCLUSIONS: The data therefore provide direct evidence for the role of beta-Sitosterol triacontenate as a potent antimetastatic agent, which can markedly inhibit the metastatic and invasive capacity of malignant cells. PMID- 22305790 TI - Content determination of benzyl glucosinolate and anti-cancer activity of its hydrolysis product in Carica papaya L. AB - OBJECTIVE: To determine the content of benzyl glucosinolate (BG) in the pulp and the seed and investigate the anti-cancer activity of its hydrolysis product in Carica papaya L. METHODS: Determination of BG was performed on an Hypersil BDS C(18) column at the wavelength of 214 nm with 0.1% trifluoroacetic acid (TFA) aqueous solution (A) and 0.1%TFA acetonitrile (B) as the mobile phase. In vitro activity test was adopted with cultured human lung cancer H69 cell in vitro to investigate the inhibition rate of cell proliferation of benzyl isothiocyanate (BITC) against H69 cell. RESULTS: The pulp has more BG before the maturation of papaya and it nearly disappeared after papaya matured, while the seed contains BG at every stage. Activity test demonstrated that the a higher concentration of BITC would have better inhibition rate of cell proliferation on H69 cell, and the IC(50) was 6.5 MUmol/L. CONCLUSIONS: BG also can be produced in the pulp of papaya and it will be stored in the seed after the fruit has been matured. The hydrolysis product of BG has certain cancer-prevention anti-cancer activities for human. PMID- 22305791 TI - Profiles of Entamoeba histolytica-specific immunoglobulins in human sera. AB - OBJECTIVE: To determine the profiles of anti-Entamoeba histolytica (E. histolytica) IgA, IgG, and IgM in sera of diarrheic and non-diarrheic individuals and partially characterize target antigens. METHODS: Serum samples from thirty diarrheic and thirty non-diarrheic individuals were subjected to IgA, IgG, and IgM profiling through enzyme-linked immunosorbent assay (ELISA), flow cytometry, and immunoblot. RESULTS: ELISA titer results showed that both diarrheic and non diarrheic individuals possess high levels of E. histolytica-specific IgG compared to IgA and IgM. Flow cytometry data showed that diarrheic serum samples had higher mean reaction percentages against E. histolytica cells compared to non diarrheic samples. Immunoreactive E. histolytica proteins with molecular weights ranging between 7 kDa and 292 kDa were recognized by diarrheic serum IgG, and 170 kDa and 250 kDa by non-diarrheic serum IgG. CONCLUSIONS: Our findings suggest that serum anti-E. histolytica IgG, compared with serum anti-E. histolytica IgA and IgM responses, was generally high in both diarrheic and non-diarrheic sera, indicating a past exposure to the organism both in symptomatic patients as well as in asymptomatic carriers, respectively. In addition, serum IgG from diarrheic and non-diarrheic patients were able to detect immunogenic E. histolytica proteins. PMID- 22305792 TI - Evaluation of serum and pleural levels of endostatin and vascular epithelial growth factor in lung cancer patients with pleural effusion. AB - OBJECTIVE: To evaluate the diagnostic value of endostatin (ES), vascular endothelial growth factor (VEGF) and carcinoembryonic antigen (CEA) in both serum and pleural effusion of lung cancer patients. METHODS: Levels of ES, VEGF and CEA in 52 malignant pleural effusion due to lung cancer and 50 patients with non malignant disease were measured by using sandwich enzyme-linked immunosorbent assay and microparticle enzyme immunoassay. RESULTS: The ES, VEGF and CEA levels in pleural effusion and serum, and their ratio (F/S) were higher in lung cancer group than that in benign group, and the differences were statistically significant (P<0.05). The diagnostic efficiency of ES+VEGF for lung cancer was superior to either single detection. The diagnostic efficiency of ES+VEGF+CEA was superior to either ES+VEGF or ES+CEA. CONCLUSIONS: The results suggest that ES, VEGF and CEA might be useful in the differentiation between benign and malignant pleural effusion due to lung cancer. In comparison with either single determination of concentration in serum or pleural fluid, the combined detection of two or three markers is of important clinical significance in the diagnosis of lung cancer. PMID- 22305793 TI - Systematic review of soy isoflavone supplements on osteoporosis in women. AB - OBJECTIVE: To clarify the effect of soy isoflavones on prevention of osteoporosis, and the effective dosage of soy isoflavones and its duration. METHODS: Random control trials that investigated the association of soy isoflavones and osteoporosis were included in the meta-analysis by researching MEDLINE, EMBASE and the Chinese Biomedical Database up to October 2011. The Rev Man software was used for all of the statistical analysis. RESULTS: The present meta-analysis found that soy isoflavones significantly increased the bone mineral density by 54% and decreased the bone resorption marker urinary deoxypyridinoline (DPD) by 23% compared to baseline in women. Using random effects model, the effect of isoflavones on bone mineral density (BMD) regarding menopausal status and isoflavone dose revealed higher weighted mean difference changes were found in postmenopausal women and isoflavone dose above 75 mg/d. Subgroup analysis of trials with menopausal status, supplement type, isoflavone dose and intervention duration that used soy isoflavone extracts resulted in significant different overall effect of DPD using by random effects model. Sensitivity analysis indicated that the effect of soy isoflavones on BMD and DPD was robust. CONCLUSIONS: The present meta-analysis reveals that soy isoflavone supplements significantly increase bone mineral density and decrease the bone resorption marker urinary DPD. It shows no significant effect on bone formation markers serum bone alkaline phosphatase. The significant effect of soy isoflavones on BMD and urinary DPD is relative to menopausal status, supplement type, isoflavone dose and intervention duration. PMID- 22305794 TI - Development of temporal modeling for prediction of dengue infection in northeastern Thailand. AB - OBJECTIVE: To model the monthly number of dengue fever cases in northeastern Thailand using time series analysis. METHODS: Autoregressive Integrated Moving Average (ARIMA) models have been developed on the monthly data collected from January 1981 to December 2006 and validated using the data from January 2007 to April 2010. RESULTS: The ARIMA (3,1,4) model has been found as the most suitable model with the least Akaike Information Criterion (AIC) of 14.060 and Mean Absolute Percent Error (MAPE) of 7.000. The model was further validated by the Portmanteau test with no significant autocorrelation between residuals at different lag times. CONCLUSIONS: Early warning based on the data in the previous months could assist in improving vector control, community intervention, and personal protection. PMID- 22305795 TI - Inverted binding due to a minor structural change in berberine enhances its phospholipase A2 inhibitory effect. AB - Biotransformation of berberine by Rhizopus oryzae leads to its demethylation, producing hydroxyl derivatives, as revealed by Fourier Transform Infra Red spectroscopy, Nuclear Magnetic Resonance and Electro Spray Ionization-Mass Spectrometric analyses. Surface Plasmon Resonance and enzyme kinetic studies showed that biotransformed derivatives of berberine had a higher inhibitory potential than berberine towards phospholipase A(2). X-ray crystal structures demonstrated that biotransformed berberine binds to PLA(2) in an entirely different, inverted orientation with respect to the binding of berberine. This study brings out the significance of biotransformation in generation of better drug-lead compounds. PMID- 22305796 TI - DNA template-assisted modulation of horseradish peroxidase activity. AB - The precise alignment of DNA molecules by Watson-Crick base-pairing combined with its polymeric characteristics have allowed DNA to be used as a template or scaffold for assembling materials. In this work, we investigate the role of calf thymus DNA as a template for enhancing the horseradish peroxidase (HRP)-mediated oxidation of phenol and phenolic derivatives. The HRP-catalyzed oxidation of phenol into polyphenolic products and in presence of 4-aminoantipyrine into quinoneimine dye complexes is studied. Visible spectroscopy reveals an increased yield of both products of the enzymatic reaction in presence of calf-thymus DNA and is attributed to the prearrangement of the corresponding substrates on the DNA. The concentrations of calf-thymus DNA and the substrates are found to affect the nature of prearrangement and subsequent formation of polymeric or co oxidation products. Also, phenolic derivatives with different aromatic substitutions display divergent propensities towards product formation in presence of the DNA template. Our results demonstrate the ability of calf-thymus DNA to modulate the activity of HRP and exercise control on the nature of products formed. This work highlights the potential of using DNA as a template for influencing enzymatic reactions involving aromatic substrates. PMID- 22305797 TI - Cerebral infarct in a patient with a history of systemic arterial and venous thrombosis from essential thrombocythemia. AB - Although essential thrombocythemia (ET) may involve thrombotic complications, including arterial or venous thrombosis, there are no reports of major vascular complications, including both arterial and venous thrombosis, in a patient with ET. We report on a patient with a cerebral infarction affecting the right lateral thalamus and a stenotic lesion of the right posterior cerebral artery. This arterial thrombotic event may be related to ET, which was based on results of a bone marrow biopsy specimen. The patient had experienced previous events of thrombosis, splenic infarction with venous thrombosis, and myocardial infarction. The cause of recurrent ischemic events involving both arterial and venous systems may be sustained elevation of platelet counts. Previous thrombosis is an established risk factor for rethrombosis in patients with ET. Efficient cytoreductive therapy with an antiplatelet agent should be considered for the prevention of recurrent thrombosis. PMID- 22305798 TI - Mobile elogbook app for maxillofacial trainees. PMID- 22305799 TI - The cytoplasmic tyrosine kinase Arg regulates gastrulation via control of actin organization. AB - Coordinated cell movements are crucial for vertebrate gastrulation and are controlled by multiple signals. Although many factors are shown to mediate non canonical Wnt pathways to regulate cell polarity and intercalation during gastrulation, signaling molecules acting in other pathways are less investigated and the connections between various signals and cytoskeleton are not well understood. In this study, we show that the cytoplasmic tyrosine kinase Arg modulates gastrulation movements through control of actin remodeling. Arg is expressed in the dorsal mesoderm at the onset of gastrulation, and both gain- and loss-of-function of Arg disrupted axial development in Xenopus embryos. Arg controlled migration of anterior mesendoderm, influenced cell decision on individual versus collective migration, and modulated spreading and protrusive activities of anterior mesendodermal cells. Arg also regulated convergent extension of the trunk mesoderm by influencing cell intercalation behaviors. Arg modulated actin organization to control dynamic F-actin distribution at the cell cell contact or in membrane protrusions. The functions of Arg required an intact tyrosine kinase domain but not the actin-binding motifs in its carboxyl terminus. Arg acted downstream of receptor tyrosine kinases to regulate phosphorylation of endogenous CrkII and paxillin, adaptor proteins involved in activation of Rho family GTPases and actin reorganization. Our data demonstrate that Arg is a crucial cytoplasmic signaling molecule that controls dynamic actin remodeling and mesodermal cell behaviors during Xenopus gastrulation. PMID- 22305800 TI - Neural crest induction at the neural plate border in vertebrates. AB - The neural crest is a transient and multipotent cell population arising at the edge of the neural plate in vertebrates. Recent findings highlight that neural crest patterning is initiated during gastrulation, i.e. earlier than classically described, in a progenitor domain named the neural border. This chapter reviews the dynamic and complex molecular interactions underlying neural border formation and neural crest emergence. PMID- 22305801 TI - Cognitive and clinical characteristics of patients with amyotrophic lateral sclerosis carrying a C9orf72 repeat expansion: a population-based cohort study. AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of upper and lower motor neurons, associated with frontotemporal dementia (FTD) in about 14% of incident cases. We assessed the frequency of the recently identified C9orf72 repeat expansion in familial and apparently sporadic cases of ALS and characterised the cognitive and clinical phenotype of patients with this expansion. METHODS: A population-based register of patients with ALS has been in operation in Ireland since 1995, and an associated DNA bank has been in place since 1999. 435 representative DNA samples from the bank were screened using repeat-primed PCR for the presence of a GGGGCC repeat expansion in C9orf72. We assessed clinical, cognitive, behavioural, MRI, and survival data from 191 (44%) of these patients, who comprised a population based incident group and had previously participated in a longitudinal study of cognitive and behavioural changes in ALS. FINDINGS: Samples from the DNA bank included 49 cases of known familial ALS and 386 apparently sporadic cases. Of these samples, 20 (41%) cases of familial ALS and 19 (5%) cases of apparently sporadic ALS had the C9orf72 repeat expansion. Of the 191 patients for whom phenotype data were available, 21 (11%) had the repeat expansion. Age at disease onset was lower in patients with the repeat expansion (mean 56.3 [SD 8.3] years) than in those without (61.3 [10.6] years; p=0.043). A family history of ALS or FTD was present in 18 (86%) of those with the repeat expansion. Patients with the repeat expansion had significantly more co-morbid FTD than patients without the repeat (50%vs 12%), and a distinct pattern of non-motor cortex changes on high resolution 3 T magnetic resonance structural neuroimaging. Age-matched univariate analysis showed shorter survival (20 months vs 26 months) in patients with the repeat expansion. Multivariable analysis showed an increased hazard rate of 1.9 (95% 1.1-3.7; p=0.035) in those patients with the repeat expansion compared with patients without the expansion INTERPRETATION: Patients with ALS and the C9orf72 repeat expansion seem to present a recognisable phenotype characterised by earlier disease onset, the presence of cognitive and behavioural impairment, specific neuroimaging changes, a family history of neurodegeneration with autosomal dominant inheritance, and reduced survival. Recognition of patients with ALS who carry an expanded repeat is likely to be important in the context of appropriate disease management, stratification in clinical trials, and in recognition of other related phenotypes in family members. FUNDING: Health Seventh Framework Programme, Health Research Board, Research Motor Neuron, Irish Motor Neuron Disease Association, The Motor Neurone Disease Association of Great Britain and Northern Ireland, ALS Association. PMID- 22305802 TI - Amyloid-related imaging abnormalities in patients with Alzheimer's disease treated with bapineuzumab: a retrospective analysis. AB - BACKGROUND: Amyloid-related imaging abnormalities (ARIA) have been reported in patients with Alzheimer's disease treated with bapineuzumab, a humanised monoclonal antibody against amyloid beta. ARIA include MRI signal abnormalities suggestive of vasogenic oedema and sulcal effusions (ARIA-E) and microhaemorrhages and haemosiderin deposits (ARIA-H). Our aim was to investigate the incidence of ARIA during treatment with bapineuzumab, and evaluate associated risk factors. METHODS: Two neuroradiologists independently reviewed 2572 fluid attenuated inversion recovery (FLAIR) MRI scans from 262 participants in two phase 2 studies of bapineuzumab and an open-label extension study. Readers were masked to the patient's treatment, APOE E4 genotype, medical history, and demographics. Patients were included in risk analyses if they had no evidence of ARIA-E in their pre-treatment MRI, had received bapineuzumab, and had at least one MRI scan after treatment. We used Kaplan-Meier survival analysis to examine the distribution of incident ARIA-E from the start of bapineuzumab treatment and proportional hazards regression models to assess risk factors associated with ARIA. FINDINGS: 210 patients were included in the risk analyses. 36 patients (17%) developed ARIA-E during treatment with bapineuzumab; 15 of these ARIA-E cases (42%) had not been detected previously. 28 of these patients (78%) did not report associated symptoms. Adverse events, reported in eight symptomatic patients, included headache, confusion, and neuropsychiatric and gastrointestinal symptoms. Incident ARIA-H occurred in 17 of the patients with ARIA-E (47%), compared with seven of 177 (4%) patients without ARIA-E. 13 of the 15 patients in whom ARIA were detected in our study received additional treatment infusions while ARIA-E were present, without any associated symptoms. Occurrence of ARIA-E increased with bapineuzumab dose (hazard ratio [HR] 2.24 per 1 mg/kg increase in dose, 95% CI 1.40-3.62; p=0.0008) and presence of APOE E4 alleles (HR 2.55 per allele, 95% CI 1.57-4.12; p=0.0001). INTERPRETATION: ARIA consist of a spectrum of imaging findings with variable clinical correlates, and some patients with ARIA-E remain asymptomatic even if treatment is continued. The increased risk of ARIA among APOE E4 carriers, its association with high bapineuzumab dose, and its timecourse in relation to dosing suggest an association between ARIA and alterations in vascular amyloid burden. FUNDING: Elan Corporation, Janssen Alzheimer Immunotherapy, Wyeth Pharmaceuticals, and Pfizer. PMID- 22305803 TI - Mutation in C9orf72 changes the boundaries of ALS and FTD. PMID- 22305804 TI - Metallobiology of host-pathogen interactions: an intoxicating new insight. AB - Iron, zinc and copper, among others, are transition metals with multiple biological roles that make them essential elements for life. Beyond the strict requirement of transition metals by the vertebrate immune system for its proper functioning, novel mechanisms involving direct metal intoxication of microorganisms are starting to be unveiled as important components of the immune system, in particular against Mycobacterium tuberculosis. In parallel, metal detoxification systems in bacteria have been recently characterized as crucial microbial virulence determinants. Here, we will focus on these exciting advancements implicating copper- and zinc-mediated microbial poisoning as a novel innate immune mechanism against microbial pathogens, shedding light on an emerging field in the metallobiology of host-pathogen interactions. PMID- 22305805 TI - Coping with health care expenses among poor households: evidence from a rural commune in Vietnam. AB - With the 1980s "Doi Moi" economic reforms, Vietnam transitioned from state-funded health care to a privatized user fee system. Out-of-pocket payments became a major source of funding for treatments received at both public and private health facilities. We studied coping strategies used by residents of Dai Dong, a rural commune of Hanoi, for paying health care costs, assessing the effects of such costs on economic and health stability. We developed a 2008 survey of 706 households (166 poor, 184 near-poor, 356 non-poor; 100% response rate). Outcome measures were reported episodes of illness; inpatient, outpatient, and self treatments; out-of-pocket expenditures; and funding sources for health care costs. Households of all income levels borrowed to pay for inpatient treatments; loans are also more heavily used by the poor and near-poor than the non-poor for outpatient treatments. Compared to low cost treatments, the use of loans is intensified for extremely high cost health treatments for all poverty levels, but especially for the poor and near-poor. The likelihood of reducing food consumption to pay for extremely high cost treatment versus low cost treatments increased most for the poor in both inpatient and outpatient contexts. Decreased funding and increased costs in health care rendered Dai Dong's population vulnerable to the consequences of detrimental coping strategies such as debt and food reduction. Future reforms should focus on obviating these funding measures among at-risk populations. PMID- 22305806 TI - 'Doing the "right" thing': how parents experience and manage decision-making for children's 'normalising' surgeries. AB - Using cleft lip and palate as an exemplar, this article examines parents' decision-making for children in the context of elective treatments which aim to 'normalise' a child's function, appearance, communication or identity. Using purposive and theoretical sampling, 35 parents with children from infancy to young adulthood were recruited through a specialist cleft centre in England. Parents were interviewed in-depth between 2006 and 2008 about their beliefs and motivations in relation to treatment decision-making in this context. A grounded theory approach was used to analyse the data. Findings revealed a core category, 'doing the "right" thing', that encapsulated parents' main concern in relation to their children's treatment and highlighted several emotional, social and cultural considerations underpinning their decision-making stance. Parents fulfilled a perceived 'moral' obligation to be 'good' parents by pursuing the 'normalising' treatments, particularly surgeries, made available to their children. Such treatments were viewed as a way of facilitating their child's social inclusion and helping them reach their full potential. In order to enable their continued pursuit of treatments over the long-term, parents also constructed specialist practitioners as highly competent and particularly trustworthy. This article captures the complexities involved in parents' decision-making for children's elective 'normalising' treatments, where both functional and appearance-related concerns are involved. It suggests that social norms about parenting, physical appearance and healthcare practitioner power may significantly shape decision making in this context, so that such choices may be viewed primarily as 'moral' rather than social. Services could support parents with such challenges, by gauging their needs for information about surgery and its likely outcomes and providing emotional/decisional support to consider all available options. PMID- 22305807 TI - Social determinants of health--a question of social or economic capital? Interaction effects of socioeconomic factors on health outcomes. AB - Social structures and socioeconomic patterns are the major determinants of population health. However, very few previous studies have simultaneously analysed the "social" and the "economic" indicators when addressing social determinants of health. We focus on the relevance of economic and social capital as health determinants by analysing various indicators. The aim of this paper was to analyse independent associations, and interactions, of lack of economic capital (economic hardships) and social capital (social participation, interpersonal and political/institutional trust) on various health outcomes. Data was derived from the 2009 Swedish National Survey of Public Health, based on a randomly selected representative sample of 23,153 men and 28,261 women aged 16-84 year, with a participation rate of 53.8%. Economic hardships were measured by a combined economic hardships measure including low household income, inability to meet expenses and lacking cash reserves. Social capital was measured by social participation, interpersonal (horizontal) trust and political (vertical/institutional trust) trust in parliament. Health outcomes included; (i) self-rated health, (i) psychological distress (GHQ-12) and (iii) musculoskeletal disorders. Results from multivariate logistic regression show that both measures of economic capital and low social capital were significantly associated with poor health status, with only a few exceptions. Significant interactive effects measured as synergy index were observed between economic hardships and all various types of social capital. The synergy indices ranged from 1.4 to 2.3. The present study adds to the evidence that both economic hardships and social capital contribute to a range of different health outcomes. Furthermore, when combined they potentiate the risk of poor health. PMID- 22305808 TI - The impact on kinesiophobia (fear of movement) by clinical variables for patients with coronary artery disease. AB - BACKGROUND: The impact on kinesiophobia (fear of movement) for patients with coronary artery disease (CAD) is not known. The aims were to describe the occurrence of kinesiophobia in patients with CAD, and to investigate the influence on kinesiophobia by clinical variables. MATERIALS AND METHODS: In total, 332 patients, mean age, 65 +/- 9.1 years diagnosed with CAD at a university hospital were included in the study. The Tampa Scale for Kinesiophobia Heart (TSK-SV Heart) was used to assess kinesiophobia. Comparisons between high versus low levels of kinesiophobia were measured for each variable. Binary logistic regression analyses were performed with a high level of kinesiophobia (TSK-SV Heart>37) as dependent variable, and with the observed variables as independent. The study had an exploratory, cross-sectional design. RESULTS: A high level of kinesiophobia was found in 20% of the patients. The following variables decreased the odds ratio (OR) for a high level of kinesiophobia: Attending cardiac rehabilitation (yes vs no: -56.7%), level of physical activity (medium vs high: -80.8%), Short-Form 36: general health (-4.3%), physical functioning (-1.8%). Two variables increased the OR for a high level of kinesiophobia: heart failure as complication at hospital (yes vs no: 418.7%), anxiety (19.2%). Previous heart failure (yes vs no) was unexpectedly found to reduce kinesiophobia (-88.3%) due to suppression. CONCLUSIONS: Several important clinical findings with impact on rehabilitation and prognosis for patients with CAD were found to be associated with a high level of kinesiophobia. Therefore, kinesiophobia needs to be considered in secondary prevention for patients with CAD. PMID- 22305809 TI - Probucol for the prevention of cystatin C-based contrast-induced acute kidney injury following primary or urgent angioplasty: a randomized, controlled trial. AB - BACKGROUND: Probucol, a lipid-lowering drug with potent antioxidant properties, may reduce the risk of cystatin C (CyC)-based contrast-induced acute kidney injury (CIAKI). The aim of this study was to observe the incidence of CyC-based CIAKI and assess the efficacy of probucol on prevention of CIAKI following primary or urgent coronary angioplasty. METHODS: A total of 204 patients with acute coronary syndrome (ACS) were prospectively randomized to a control group (108 patients, 74 male, 65.4 +/- 12.5 years) or probucol group (96 patients, 67 male, 65.1 +/- 10.5 years) 1000 mg orally before primary or urgent angioplasty and 500 mg twice daily for 3 days following intervention. Serum CyC and serum creatinine (Scr) concentrations were measured before, and on day 1, day 2 and day 3 after coronary intervention. RESULTS: The clinical characteristics of the patients from the two groups were similar. Scr-based CIAKI was developed in 23 patients of the control group (21.3%) and in 4 patients of the probucol group (4.2%) (P<0.001). Furthermore, CyC-based CIAKI occurred in 56 patients of the control group (51.9%) and 28 patients of the probucol group (29.2%) (P<0.001). The CyC increase >= 10% after exposure to contrast medium was the best increment cutoff value for the early identification of patients at risk of CIAKI. CONCLUSIONS: Our study suggests that CyC is a reliable marker for early identification and ruling out the patients at the risk of CIAKI. Among the patients with ACS who are undergoing primary or urgent angioplasty, prophylactic treatment with probucol reduces the risk of both Scr and CyC-based CIAKI. PMID- 22305810 TI - Atrial fibrillation, complete atrioventricular block and escape rhythm with bundle-branch block morphologies: an exceptional presentation of Lyme carditis. PMID- 22305811 TI - Red blood cell transfusion and mortality among patients hospitalized for acute coronary syndromes: a systematic review. AB - BACKGROUND: Observational studies have suggested a relationship between anemia and adverse outcomes among patients presenting with acute coronary syndromes (ACS). However, the hemoglobin level at which packed red blood cell (PRBC) transfusion is beneficial remains unclear as available data are conflicting. We therefore performed a systematic review of all relevant observational studies, with a particular focus on examining optimum hemoglobin thresholds for transfusion among patients hospitalized for ACS. METHODS: We systematically searched MEDLINE, as well as relevant bibliographies, to identify all observational studies examining the effects of PRBC transfusion among post-ACS patients. Inclusion was restricted to English language studies that reported data for the risk of mortality, congestive heart failure (CHF), or recurrent myocardial infarction (MI). RESULTS: We identified 11 studies that met our inclusion criteria, involving a total of 290,847 patients. When reported, the main indication for transfusion appeared to be major bleeding. Overall, patients who received transfusions were at greater unadjusted risk of mortality (range of odds ratio [OR]: 1.9 to 11.2). When hemoglobin-stratified analyses were examined, a graded association between PRBC transfusion and mortality was seen, wherein transfusion had beneficial or neutral effects on mortality below 8.0g/dL, and harmful or neutral effects above 11.0g/dL. CONCLUSIONS: PRBC transfusion in patients post-ACS undertaken at hemoglobin levels below 8.0g/dL was found to be beneficial or, at worst, neutral. Conversely, there was suggestion of harm when transfusion was undertaken at hemoglobin levels above 11.0g/dL, supporting a more conservative transfusion strategy. PMID- 22305812 TI - A bleeding conundrum. PMID- 22305813 TI - Dual non-responsiveness to antiplatelet treatment is a stronger predictor of cardiac adverse events than isolated non-responsiveness to clopidogrel or aspirin. AB - BACKGROUND: High platelet reactivity (HPR) under treatment with clopidogrel or aspirin is associated with adverse outcome. We aimed to investigate whether high platelet reactivity (HPR) to both aspirin and clopidogrel is a stronger predictor of adverse events compared to isolated HPR to clopidogrel or aspirin. METHODS: In this prospective cohort study platelet reactivity to adenosine diphosphate (ADP) and arachidonic acid (AA) was assessed by Multiple Electrode Aggregometry (MEA) in 403 patients undergoing percutaneous coronary intervention. The rates of the composite of cardiac adverse events (acute coronary syndrome, stent thrombosis, stroke, death and revascularization) were recorded during 12-month follow-up. RESULTS: The composite endpoint of cardiovascular adverse events occurred more often in patients with high platelet reactivity (HPR) to both agonists ADP and AA (37.5%) than in those with isolated HPR to ADP (33.3%), AA (25.6%) or without any HPR (18.6%; p=0.003). Classification tree analysis indicated that any HPR emerged as an independent predictor influencing outcome, which was associated with a 1.75 higher risk of cardiac adverse events (OR=1.75: 95%CI=1.1-2.9). Interestingly, the predictive value of HPR tended to be greater among patients with diabetes mellitus (OR=2.18; 95%CI=1.20-3.95). C-reactive protein and diabetes mellitus were independent predictors of high platelet reactivity to both agonists. CONCLUSIONS: Dual low responsiveness to clopidogrel and aspirin is a strong predictor of cardiac adverse events, especially in patients with diabetes mellitus, which underlines the need for personalized antiplatelet treatment. PMID- 22305814 TI - Circulating carboxy-terminal propeptide of type I procollagen is increased in rheumatic heart disease. PMID- 22305815 TI - Reply to the letter regarding Flecher et al. "cancer on a pacemaker lead": is it MICE (Mesothelial Incidental Excrescence). PMID- 22305816 TI - The presence of an atrial electromechanical delay in idiopathic atrial fibrillation as determined by tissue Doppler imaging. PMID- 22305817 TI - The prognostic value of very low admission LDL-cholesterol levels in ST-segment elevation myocardial infarction compared in statin-pretreated and statin-naive patients undergoing primary percutaneous coronary intervention. AB - BACKGROUND: Some recent trials reported that, low admission low-density lipoprotein-cholesterol (LDL-C) levels were associated with increased mortality in patients with acute coronary syndromes. We aimed to compare the effect of very low admission LDL-C levels on prognosis in statin-pretreated and statin-naive patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary angioplasty. METHODS: The study population consisted of 1808 patients with acute STEMIs who underwent primary angioplasty. The patients were categorized into four groups as: statin-pretreated/LDL-C<70 mg/dl (n=128), statin pretreated/LDL-C >= 70 mg/dl (n=290), statin-naive/LDL-C <70 mg/dl (n=146), statin-naive/LDL-C >= 70 mg/dl (n=1244). The median follow-up was 40 months. RESULTS: The incidences of diabetes mellitus, hypertension, renal insufficiency, anemia, cardiogenic shock on presentation and the mean age were significantly higher in the statin-naive/LDL-C < 70 mg/dl group. In-hospital (2.3% vs 2.4% vs 12.3% vs 3.9%, respectively p<0.001) and long-term mortalities (6.3% vs 7.3% vs 25.9% vs 11.3% respectively, p<0.001) were significantly lower in the "statin pretreated/LDL-C<70" group. Statin pretreatment was independently predicting lower long-term mortality irrespective of LDL-C level [for the subgroup with LDL C < 70 mg/dl, Hazard Ratio (HR) 0.24, 95% CI 0.10-0.59, p=0.013; for the subgroup with LDL-C >= 70 mg/dl, HR 0.31, 95% CI 0.14-0.83, p=0.022]. LDL-C levels on admission had no independent predictive role on long-term mortality. CONCLUSIONS: Statin induced low LDL-C levels on admission are associated with better short- and long-term outcomes in patients with STEMI and independently predict lower long-term mortality. However, spontaneously low admission LDL-C levels were associated with increased short- and long-term mortalities. PMID- 22305818 TI - Metabolic syndrome in Spain: prevalence and coronary risk associated with harmonized definition and WHO proposal. DARIOS study. AB - INTRODUCTION AND OBJECTIVES: To update the prevalence of metabolic syndrome and associated coronary risk in Spain, using the harmonized definition and the new World Health Organization proposal (metabolic premorbid syndrome), which excludes diabetes mellitus and cardiovascular disease. METHODS: Individual data pooled analysis study of 24,670 individuals from 10 autonomous communities aged 35 to 74 years. Coronary risk was estimated using the REGICOR function. RESULTS: Prevalence of metabolic syndrome was 31% (women 29% [95% confidence interval, 25% 33%], men 32% [95% confidence interval, 29%-35%]). High blood glucose (P=.019) and triglycerides (P<.001) were more frequent in men with metabolic syndrome, but abdominal obesity (P<.001) and low high-density lipoprotein cholesterol (P=.001) predominated in women. Individuals with metabolic syndrome showed moderate coronary risk (8% men, 5% women), although values were higher (P<.001) than in the population without the syndrome (4% men, 2% women). Women and men with metabolic syndrome had 2.5 and 2 times higher levels of coronary risk, respectively (P<.001). Prevalence of metabolic premorbid syndrome was 24% and the increase in coronary risk was also proportionately larger in women than in men (2 vs 1.5, respectively; P<.001). CONCLUSIONS: Prevalence of metabolic syndrome is 31%; metabolic premorbid syndrome lowers this prevalence to 24% and delimits the population for primary prevention. The increase in coronary risk is proportionally larger in women, in both metabolic syndrome and metabolic premorbid syndrome. PMID- 22305819 TI - Renal insufficiency and vascular complications after primary angioplasty via femoral route. Impact of vascular closure devices use. AB - INTRODUCTION AND OBJECTIVES: We sought to determine the incidence of vascular complications in patients with chronic kidney disease undergoing primary angioplasty via the femoral route; we also evaluated the safety and efficacy of the use of vascular closure devices in this setting. METHODS: Registry of 527 patients undergoing primary angioplasty via the femoral route from January 2003 to December 2008. Chronic kidney disease was defined as creatinine clearance less than 60 mL/min. The primary endpoint was the presence of major vascular complications. RESULTS: Baseline chronic kidney disease was observed in 166 (31.5%) patients. Patients with chronic kidney disease experienced higher rates of major vascular complications compared to those without worsening of renal function (8.4% vs 4.2%; P=.045), especially those requiring transfusion (6.6% vs 1.9%; P=.006). Among patients with chronic kidney disease, 129 (77.7%) received a vascular closure device and manual compression was used in 37 patients (22.3%). The risk of major vascular complications was significantly lower with vascular closure device use compared to manual compression (4.7% vs 21.6%; P=.003). Multivariable logistic regression analysis showed that the use of a vascular closure device was independently associated with a decreased risk of major vascular complications in patients with chronic kidney disease undergoing primary angioplasty (odds ratio=0.11; 95% confidence interval, 0.03-0.41; P=.001). CONCLUSIONS: Patients with chronic kidney disease undergoing primary angioplasty via the femoral route experience higher rates of major vascular complications. The use of vascular closure devices in this group of patients is safe and is associated with lower rates of major vascular complications compared to manual compression. PMID- 22305820 TI - Circulating microparticles from patients with coronary artery disease cause endothelial dysfunction. PMID- 22305821 TI - Current percutaneous recanalization of coronary chronic total occlusion. AB - Although successful recanalization rates of coronary chronic total occlusions have remained suboptimal in percutaneous coronary interventions, evolving techniques, including the retrograde approach, have raised hopes for better outcomes. With the advent of antiplatelet therapy and drug-eluting stents, along with conventional antegrade approaches, further progress can be expected in the "last frontier" of interventional cardiology. The article focuses on contemporary recanalization strategy in percutaneous coronary intervention of coronary chronic total occlusions. PMID- 22305822 TI - The origin of the tRNA molecule: Independent data favor a specific model of its evolution. AB - The properties, historical and empirical observations of a model of the origin of the tRNA molecule are discussed. This model would predict that this molecule originated by means of the assembly of two hairpin-like structures of RNA. The conclusion is that the model possesses a relevant part of the truth on the origin of the tRNA molecule. PMID- 22305823 TI - Surgical patient advocacy: role and value in surgery. AB - Patient advocacy may be necessary during medical care in the home or office as well as during hospitalization in either private or public sector care. Patients may choose a relative, a close friend or a physician as their patient advocate. The patient advocate may provide physical assistance and usually accompanies the patient throughout the course of disease. By agreeing to the presence of a patient advocate during visits, the patient implicitly acknowledges that confidentiality may be breached. Patient advocates may be particularly useful for the patient in case of severe disease or poor prognosis. The advocate becomes an intermediary contact and, at the same time, provides educational, relational and psychological support for the patient. The patient advocate should be consulted when the patient is incapable of making his own decisions. The patient advocate is supposed to be able to express the wishes of the patient, when the latter is incapable of doing so. The patient should therefore choose someone who, in his judgment, is competent to voice the patient's opinion for him. When the patient advocate remains at the patient's side at the end of life, whether in the hospital or at the patient's home, the advocate can benefit from "family solidarity leave" and obtain a daily stipend if this interrupts his or her professional activity. PMID- 22305824 TI - Five- to 18-year follow-up for treatment of trapeziometacarpal osteoarthritis: a prospective comparison of excision, tendon interposition, and ligament reconstruction and tendon interposition. AB - PURPOSE: To investigate whether palmaris longus interposition or flexor carpi radialis ligament reconstruction and tendon interposition improve the outcome of trapezial excision for the treatment of basal joint arthritis after a minimum follow-up of 5 years. METHODS: We randomized 174 thumbs with trapeziometacarpal osteoarthritis into 3 groups to undergo simple trapeziectomy, trapeziectomy with palmaris longus interposition, or trapeziectomy with ligament reconstruction and tendon interposition using 50% of the flexor carpi radialis tendon. A K-wire was passed across the trapezial void and retained for 4 weeks, and a thumb spica was used for 6 weeks in all 3 groups. We reviewed 153 thumbs after a minimum of 5 years (median, 6 y; range, 5-18 y) after surgery with subjective and objective assessments of thumb pain, function, and strength. RESULTS: There was no difference in the pain relief achieved in the 3 treatment groups, with good results in 120 (78%) patients. Grip strength and key and tip pinch strengths did not differ among the 3 groups and range of movement of the thumb was similar. Few complications persisted after 5 years, and these were distributed evenly among the 3 groups. Compared with the results at 1 year in the same group of patients, the good pain relief achieved was maintained in the longer term, irrespective of the type of surgery. While improvements in grip strength achieved at 1 year after surgery were preserved, the key and tip pinch strengths deteriorated with time, but the type of surgery did not influence this. CONCLUSIONS: The outcomes of these 3 variations of trapeziectomy were similar after a minimum follow-up of 5 years. There appears to be no benefit to tendon interposition or ligament reconstruction in the longer term. PMID- 22305825 TI - Intraoperative imaging of the distal radioulnar joint using a modified skyline view. AB - PURPOSE: Nonanatomic reduction of the sigmoid notch in distal radius fractures may lead to limited motion, instability, or pain with pronation and supination. Standard radiological projections only poorly capture the sigmoid notch contours in the axial plane. The purpose of this study was to find an intraoperatively feasible radiological projection that will facilitate an axial view of the distal radioulnar joint. METHODS: We modified a previously described radiographic projection termed the skyline view for evaluating the distal radius axially. We created intra-articular steps at the sigmoid notch in solid foam forearm models to identify the best of 12 projections using an image intensifier. Four observers scored each projection based on the clarity of the sigmoid notch contour and indicated the presence and location of an intra-articular stepoff. RESULTS: The sigmoid notch was best visualized in the modified skyline view with the wrist in extension and 10 degrees to 15 degrees of dorsal forearm angulation relative to the x-ray path. All observers correctly recognized the presence and location of intra-articular steps at the sigmoid notch with this view. The same forearm angulation with the wrist in flexion did not reach equally good visibility of the sigmoid notch. Arm position (wrist flexion, forearm rotation, or forearm angulation) and intra-articular stepoff (none, palmar, or dorsal) were dependent determinates. Elimination of the variable forearm rotation had minimal effect, indicating that forearm rotation is not important for visualization of the sigmoid notch. CONCLUSIONS: The modified skyline view for visualization of the distal radioulnar joint in an axial plane allows good visibility of the sigmoid notch and reliable identification of stepoffs. Further cadaver and in vivo studies are required to verify the validity of this method. PMID- 22305826 TI - Corrective osteotomy and ligament repair for longstanding radial collateral ligament tear of the proximal interphalangeal joint: case series. AB - PURPOSE: To evaluate the clinical outcomes of corrective osteotomy and ligament repair for longstanding radial collateral ligament tears of the proximal interphalangeal (PIP) joint. METHODS: We retrospectively evaluated 4 patients with 5 longstanding tears in the radial collateral ligaments of the PIP joints. The average age at the time of surgery was 51 years (range, 40-62 y). The average time from the initial injury to surgery was 31 years (range, 22-40 y). Plain radiographs revealed an ulnar slope at the PIP joint surface with degenerative changes in all fingers. We corrected the slope using a closing wedge osteotomy of the neck of the proximal phalanx secured with a headless screw. We then repaired the radial collateral ligament by overlapping the elongated ligament. Range of motion exercises were started 2 weeks after surgery. To evaluate the results, we compared preoperative and postoperative range of motion, ulnar deviation, instability, pain, and level of satisfaction. Average follow-up was 27 months (range, 18-48 mo). RESULTS: All osteotomies had united at an average of 3 months. We observed no major changes in range of motion, but flexion contracture gradually appeared in 1 high-demand patient. The average preoperative angle of ulnar deviation was 36 degrees and was corrected to a postoperative angle of 2 degrees . The average angle of lateral instability improved after surgery from 22 degrees to 1 degrees . Finger pain disappeared or decreased in 3 low-demand patients but persisted in 1 high-demand patient. Two low-demand patients were very satisfied and 1 low-demand patient was satisfied; however, 1 high-demand patient was dissatisfied with the results of surgery. CONCLUSIONS: Corrective osteotomy and ligament repair can result in a straight and stable joint with a good range of motion in low-demand patients. This method could be a treatment option for carefully selected patients. PMID- 22305827 TI - A case where the principle of "one question, one answer" may work better. PMID- 22305828 TI - Newest-generation drug-eluting and bare-metal stents combined with prasugrel based antiplatelet therapy in large coronary arteries: the BAsel Stent Kosten Effektivitats Trial PROspective Validation Examination part II (BASKET-PROVE II) trial design. AB - BACKGROUND: In the BAsel Stent Kosten Effektivitats Trial PROspective Validation Examination (BASKET-PROVE), drug-eluting stents (DESs) had similar 2-year rates of death and myocardial infarction but lower rates of target vessel revascularization and major adverse cardiac events compared with bare-metal stents (BMSs). However, comparative clinical effects of newest-generation DES with biodegradable polymers vs second-generation DES or newest-generation BMS with biocompatible coatings, all combined with a prasugrel-based antiplatelet therapy, on 2-year outcomes are not known. METHODS: In BASKET-PROVE II, 2,400 patients with de novo lesions in native vessels >=3 mm in diameter are randomized 1:1:1 to receive a conventional DES, a DES with a biodegradable polymer, or a BMS with biocompatible coating. In addition to aspirin, stable patients with BMS will receive prasugrel for 1 month, whereas all others will receive prasugrel for 12 months. The primary end point will be combined cardiac death, nonfatal myocardial infarction, and target vessel revascularization up to 2 years. Secondary end points include stent thrombosis and major bleeding. The primary aim is to test (1) the noninferiority of a biodegradable-polymer DES to a conventional DES and (2) the superiority of both DESs to BMS. A secondary aim is to compare the outcomes with those of BASKET-PROVE regarding the effects of prasugrel-based vs clopidogrel-based antiplatelet therapy. RESULTS: By the end of 2010, 878 patients (37% of those planned) were enrolled. CONCLUSIONS: This study will test the comparative long-term safety and efficacy of newest-generation stents on the background of contemporary antiplatelet therapy in a large all-comer population undergoing large native coronary artery stenting. PMID- 22305829 TI - Rationale and design of the TAXUS Liberte Post-Approval Study: examination of patients receiving the TAXUS Liberte stent with concomitant prasugrel therapy in routine interventional cardiology practice. AB - BACKGROUND: Observational studies of new coronary stents are necessary to assess performance in a variety of complex patient and lesion types. Furthermore, the optimal dose and duration of thienopyridine treatment is unclear, particularly in patients with complex clinical conditions. The TAXUS Liberte Post-Approval Study is designed to provide 5-year data on the TAXUS Liberte paclitaxel-eluting stent with concomitant prasugrel therapy in routine clinical practice and to contribute data to the DAPT study. STUDY DESIGN: The TAXUS Liberte Post-Approval Study is a prospective, multicenter, observational study. Enrollment of approximately 4,200 patients receiving >=1 TAXUS Liberte stents is planned. All patients without a contraindication will be prescribed prasugrel plus aspirin for 1 year. The 12 month primary end point of cardiac death or myocardial infarction in on-label stent patients will be compared with historical TAXUS Express stent data from the TAXUS ATLAS and TAXUS ARRIVE studies. Secondary clinical end points include stent thrombosis, all-cause death, stroke, revascularization, and bleeding in all patients. In addition, this study will be the first to evaluate prasugrel use in a routine practice setting (including 5 and 10 mg daily doses) and will contribute data to the DAPT Study, comparing 12 versus 30 months of dual antiplatelet therapy after drug-eluting stent placement. SUMMARY: The TAXUS Liberte Post-Approval Study will be the first to provide long-term real-world data on use of the TAXUS Liberte Stent with prasugrel treatment. The study is currently enrolling, and primary end point data are expected in mid 2013. PMID- 22305830 TI - Design of the RELAXin in acute heart failure study. AB - BACKGROUND: Acute heart failure (AHF) remains a major public health burden with a high prevalence and poor prognosis. Relaxin is a naturally occurring peptide hormone that increases cardiac output, arterial compliance, and renal blood flow during pregnancy. The RELAX-AHF-1 study will evaluate the effect of RLX030 (recombinant form of human relaxin 2) on symptom relief and clinical outcomes in patients with AHF. METHODS: The protocol includes a completed phase 2 234-patient dose-finding study (Pre-RELAX-AHF) and an ongoing phase 3 1,160-patient trial (RELAX-AHF-1). Patients with AHF and systolic blood pressure >125 mm Hg are randomized within 16 hours of presentation to a 48-hour IV infusion of RLX030 or placebo. The 30 MUg/kg per day dose of RLX030 was chosen for RELAX-AHF-1 based on effects on dyspnea, clinical outcomes, and safety observed in Pre-RELAX-AHF. Primary efficacy end points in RELAX-AHF-1 are (1) the area under the curve of change of the dyspnea Visual Analog Scale from baseline through day 5 and (2) whether the patient reports moderately to markedly better dyspnea at 6, 12, and 24 hours. Secondary efficacy end points include days alive and out of the hospital through day 60 and cardiovascular death or rehospitalization for heart failure or renal failure through day 60. Patients will be followed up through day 180 for mortality. As of September 19, 2011, 978 patients have been enrolled. CONCLUSIONS: Pre-RELAX-AHF results suggested that infusion of RLX030 may accelerate dyspnea relief and improve prognosis in patients hospitalized with AHF. RELAX-AHF-1 will further evaluate these effects. PMID- 22305831 TI - Management of cardiac toxicity in patients receiving vascular endothelial growth factor signaling pathway inhibitors. AB - BACKGROUND: Interfering with angiogenesis is an effective, widely used approach to cancer therapy, but antiangiogenic therapies have been associated with important systemic cardiovascular toxicities such as hypertension, left ventricular dysfunction, heart failure, and myocardial ischemia and infarction. As the use of vascular endothelial growth factor signaling pathway (VSP) inhibitors broadens to include older patients and those with existing cardiovascular disease, the adverse effects are likely to be more frequent, and cardiologists will increasingly be enlisted to help oncologists manage patients who develop adverse cardiovascular effects. METHODS: The Cardiovascular Toxicities Panel of the National Cancer Institute reviewed the published literature and abstracts from major meetings, shared experience gained during clinical development of VSP inhibitors, and contributed extensive clinical experience in evaluating and treating patients with cancer with cardiovascular disease. This report was edited and approved by the National Cancer Institute Investigational Drug Steering Committee. It presents the panel's expert opinion on the current clinical use and future investigation for safer, more expansive use of these drugs. RESULTS AND CONCLUSIONS: The panel recommends that physicians (1) conduct and document a formal risk assessment for existing cardiovascular disease and potential cardiovascular complications before VSP inhibitor treatment recognizing that preexisting hypertension and cardiovascular disease are common in patients with cancer, (2) actively monitor for blood pressure elevations and cardiac toxicity with more frequent assessments during the first treatment cycle, and (3) aggressively manage blood pressure elevations and early symptoms and signs of cardiac toxicity to prevent clinically limiting complications of VSP inhibitor therapy. PMID- 22305832 TI - Detection of periodontal bacteria in thrombi of patients with acute myocardial infarction by polymerase chain reaction. AB - BACKGROUNDS: Numerous reports have demonstrated that periodontal bacteria are present in plaques from atherosclerotic arteries. Although periodontitis has recently been recognized as a risk factor for coronary artery disease, the direct relationship between periodontal bacteria and coronary artery disease has not yet been clarified. It has been suggested that these bacteria might contribute to inflammation and plaque instability. We assumed that if periodontal bacteria induce inflammation of plaque, the bacteria would be released into the bloodstream when vulnerable plaque ruptures. To determine whether periodontal bacteria are present in thrombi at the site of acute myocardial infarction, we tried to detect periodontal bacteria in thrombi of patients with acute myocardial infarction by polymerase chain reaction (PCR). METHODS: We studied 81 consecutive adults with ST-segment elevation acute myocardial infarction who underwent primary percutaneous coronary intervention (PCI). All patients underwent removal of thrombus with aspiration catheters at the beginning of percutaneous coronary intervention, and a small sample of thrombus was obtained for PCR. RESULTS: The detection rates of periodontal bacteria by PCR were 19.7% for Aggregatibacter actinomycetemcomitans, 3.4% for Porphyromonas gingivalis, and 2.3% for Treponema denticola. CONCLUSIONS: Three species of periodontal bacteria were detected in the thrombi of patients with acute myocardial infarction. This raises the possibility that such bacteria are latently present in plaque and also suggests that these bacteria might have a role in plaque inflammation and instability. PMID- 22305833 TI - High-concentration versus titrated oxygen therapy in ST-elevation myocardial infarction: a pilot randomized controlled trial. AB - BACKGROUND: The optimal approach to oxygen therapy in ST-elevation myocardial infarction (STEMI) is uncertain. METHODS: A randomized controlled trial was undertaken in which 136 patients presenting with their first STEMI uncomplicated by cardiogenic shock or marked hypoxia were randomized to receive high concentration (6 L/min via medium concentration mask) or titrated oxygen (to achieve oxygen saturation 93%-96%) for 6 hours after presentation. The main outcome variables were 30-day mortality and infarct size assessed by troponin T level at 72 hours. Secondary outcomes included a meta-analysis of mortality data from this study and previous randomized controlled trials, and infarct size was assessed by magnetic resonance imaging at 4 to 6 weeks. RESULTS: There were 1 of 68 and 2 of 68 deaths in the high-concentration and titrated oxygen groups, respectively; a meta-analysis including these data with those from the 2 previous studies showed an odds ratio for mortality of high-concentration oxygen compared with room air or titrated oxygen of 2.2 (95% CI 0.8-6.0). There was no significant difference between high-concentration versus titrated oxygen in troponin T (ratio of mean levels 0.74, 95% CI 0.50-1.1, P = .14), infarct mass (mean difference -0.8 g, 95% CI -7.6 to 6.1, P = .82), or percent infarct mass (mean difference -0.6%, 95% CI -5.6 to 4.5, P = .83). CONCLUSION: This study found no evidence of benefit or harm from high-concentration compared with titrated oxygen in initially uncomplicated STEMI. However, our estimates have wide CIs, and as a result, large randomized controlled trials are required to resolve the clinical uncertainty. PMID- 22305834 TI - Efficacy and safety of enoxaparin compared with unfractionated heparin in the pharmacoinvasive management of acute ST-segment elevation myocardial infarction: Insights from the TRANSFER-AMI trial. AB - AIMS: An early invasive strategy after fibrinolysis for ST-elevation myocardial infarction (STEMI) improves outcomes, but the relative efficacy and safety of enoxaparin compared with unfractionated heparin (UFH) as part of this approach are unknown. METHODS AND RESULTS: In the TRANSFER-AMI trial, patients with high risk STEMI received fibrinolysis and were then randomized to either standard treatment or to immediate transfer for coronary angiography. In this substudy, the outcome of patients aged <75 years treated with enoxaparin is compared with that of patients who received UFH. Logistic regression and propensity score models were used to evaluate the efficacy and safety of these anticoagulants. Enoxaparin was administered to 498 patients, and UFH, to 448 patients, at the time of fibrinolysis. Approximately 50% in each group were randomized to the early invasive strategy. The primary composite end point of death, reinfarction, recurrent ischemia, new or worsening heart failure, or cardiogenic shock at 30 days occurred in 11.9% and 11.6% of the patients who received enoxaparin and UFH, respectively (adjusted odds ratio 0.95 [95% CI 0.60-1.51], P = .84). Enoxaparin use was associated with more access site bleeding (5.0% vs 2.9%, P = .04) and mild bleeding (12.1% vs 7.8%, P = .03). CONCLUSIONS: Among high-risk patients with STEMI undergoing early or late transfer for cardiac catheterization after fibrinolysis, enoxaparin was associated with similar efficacy compared with UFH, but there was more minor bleeding with enoxaparin (ClinicalTrials.gov no. NCT00164190). PMID- 22305835 TI - Reduced immediate ischemic events with cangrelor in PCI: a pooled analysis of the CHAMPION trials using the universal definition of myocardial infarction. AB - BACKGROUND: There is a clinical need for an intravenous P2Y(12) inhibitor in patients with acute coronary syndromes (ACS) for patients who are unable to take oral medications or might benefit from a rapidly reversible compound. As the time from admission to percutaneous coronary intervention (PCI) shortens, establishing the benefit of novel therapies impacting ischemic events is increasingly challenging. Cangrelor, an intravenous potent rapidly acting P2Y(12) inhibitor, bolus 30 MUg/Kg plus infusion of 4 MUg/Kg/min, was compared to a 600-mg loading dose of clopidogrel either before or early after PCI in patients with ACS undergoing PCI in The CHAMPION (Cangrelor versus standard tHerapy to Achieve optimal Management of Platelet InhibitiON) PLATFORM and PCI studies. METHODS: As both CHAMPION studies used similar inclusion/exclusion criteria and death, myocardial infarction, or ischemia-driven revascularization (including stent thrombosis) at 48 hours as their primary end points, the studies were pooled. The clinical events committee adjudicated myocardial infarction. The universal definition was used to define myocardial infarction. RESULTS: A total of 13 049 patients were included. Cangrelor had no effect on the primary end point with the original MI definition (P = .646). With the use of the universal definition, the primary end point was decreased with cangrelor (odds ratio 0.82, 95% confidence interval 0.68-0.99, P = .037). Stent thrombosis was reduced from 0.4% to 0.2% (odds ratio 0.44, 95% confidence interval 0.22-0.87, P = .018). Thrombolysis in Myocardial Infarction major bleeding and transfusions were not increased with cangrelor. CONCLUSION: With the use of the universal definition of myocardial infarction, cangrelor was associated with a significant reduction in early ischemic events when compared with clopidogrel in patients with non-ST-elevation ACS undergoing PCI. PMID- 22305836 TI - Statin treatment for coronary artery plaque composition based on intravascular ultrasound radiofrequency data analysis. AB - BACKGROUND: Systemic therapy with statin has been shown to lower the risk of coronary events; however, the in vivo effects of statin therapy on plaque volume and composition are less understood. METHODS: We conducted a prospective, open labeled, randomized, multicenter study in 11 centers in Japan. A total of 164 patients were randomized to receive either 4 mg/d of pitavastatin (intensive lipid-lowering therapy) or 20 mg/d of pravastatin (moderate lipid-lowering therapy). Analyzable intravascular ultrasound data were obtained for 119 patients at baseline and at 8-month follow-up. The primary end point was the difference of volume changes in each of the 4 main plaque components (fibrosis, fibrofatty, calcium, and necrosis), assessed by virtual histology intravascular ultrasound, between the 2 groups. RESULTS: The mean low-density lipoprotein cholesterol level at follow-up was significantly lower in the pitavastatin than in the pravastatin group (74 vs 95 mg/dL, P < .0001). During the 8-month follow-up period, statin therapy reduced the absolute and relative amount of fibrofatty component (pitavastatin: from 1.09 to 0.81 mm(3)/mm, P = .001; pravastatin: from 1.05 to 0.83 mm(3)/mm, P = .0008) and increased in the amount of calcium (pitavastatin: from 0.42 to 0.55 mm(3)/mm, P < .0001; pravastatin: from 0.44 to 0.55 mm(3)/mm, P = .005), whereas volume changes in both plaque components were not statistically different between the 2 groups. CONCLUSIONS: Both pitavastatin and pravastatin altered coronary artery plaque composition by significantly decreasing the fibrofatty plaque component and increasing the calcified plaque component. PMID- 22305837 TI - Single high-dose erythropoietin administration immediately after reperfusion in patients with ST-segment elevation myocardial infarction: results of the erythropoietin in myocardial infarction trial. AB - BACKGROUND: Preclinical studies and pilot clinical trials have shown that high dose erythropoietin (EPO) reduces infarct size in acute myocardial infarction. We investigated whether a single high-dose of EPO administered immediately after reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) would limit infarct size. METHODS: A total of 110 patients undergoing successful primary coronary intervention for a first STEMI was randomized to receive standard care either alone (n = 57) or combined with intravenous administration of 1,000 U/kg of epoetin beta immediately after reperfusion (n = 53). The primary end point was infarct size assessed by gadolinium-enhanced cardiac magnetic resonance after 3 months. Secondary end points included left ventricular (LV) volume and function at 5-day and 3-month follow-up, incidence of microvascular obstruction (MVO), and safety. RESULTS: Erythropoietin significantly decreased the incidence of MVO (43.4% vs 65.3% in the control group, P = .03) and reduced LV volume, mass, and function impairment at 5-day follow-up (all P < .05). After 3 months, median infarct size (interquartile range) was 17.5 g (7.6-26.1 g) in the EPO group and 16.0 g (9.4-28.2 g) in the control group (P = .64); LV mass, volume, and function were not significantly different between the 2 groups. The same number of major adverse cardiac events occurred in both groups. CONCLUSIONS: Single high-dose EPO administered immediately after successful reperfusion in patients with STEMI did not reduce infarct size at 3-month follow-up. However, this regimen decreased the incidence of MVO and was associated with transient favorable effects on LV volume and function. PMID- 22305838 TI - Circadian variations of ischemic burden among patients with myocardial infarction undergoing primary percutaneous coronary intervention. AB - BACKGROUND: Several parameters of cardiovascular physiology and pathophysiology exhibit circadian rhythms. Recently, a relation between infarct size and the time of day at which it occurs has been suggested in experimental models of myocardial infarction. The aim of this study is to investigate whether circadian rhythms could cause differences in ischemic burden in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). METHODS: In 353 consecutive patients with STEMI treated by PPCI, time of symptom onset, peak creatine kinase (CK), and follow-up at 30 days were obtained. We divided 24 hours into 4 time groups based on time of symptom onset (00:00-05:59, 06:00-11:59, 12:00-17:59, and 18:00-23:59). RESULTS: There was no difference between the groups regarding baseline patients and management's characteristics. At multivariable analysis, there was a statistically significant difference between peak CK levels among patients with symptom onset between 00:00 and 05:59 when compared with peak CK levels of patients with symptom onset in any other time group (mean increase 38.4%, P < .05). Thirty-day mortality for STEMI patients with symptom onset occurring between 00:00 and 05:59 was significantly higher than any other time group (P < .05). CONCLUSION: This study demonstrates an independent correlation between the infarct size of STEMI patients treated by PPCI and the time of the day at which symptoms occurred. These results suggest that time of the day should be a critical issue to look at when assessing prognosis of patients with myocardial infarction. PMID- 22305839 TI - Indications for percutaneous coronary interventions performed in US hospitals: a report from the NCDR(r). AB - BACKGROUND: There are many factors hypothesized as contributing to overuse of percutaneous coronary intervention (PCI) in the United States, including financial ties between physicians and hospitals, but empirical data are lacking. We examined PCI indications in not-for-profit (NFP), major teaching, for-profit (FP), and physician-owned specialty hospitals. METHODS: A retrospective cohort study of 1,113,554 patients who underwent PCI in 694 hospitals (NFP 471, teaching 131, FP 79, specialty 13) participating in the CathPCI Registry(r) between January 1, 2004, and December 31, 2007. Percutaneous coronary intervention indications derived from American College of Cardiology Guidelines were classified as survival benefit (patients with primary reperfusion for ST elevation myocardial infarction), potential quality of life benefit (patients with non-ST-elevation myocardial infarction, acute coronary syndrome (ACS), positive stress test, or chest pain), or unclear indications (patients receiving PCI without an obvious potential survival or quality of life benefit). RESULTS: The percentage of PCI performed for unclear indications was somewhat higher for specialty hospitals (5.1% of all procedures) as compared with other hospital categories (FP 4.7%, NFP 4.2%, major teaching 4.5%; P < .001). Overall, 17% of hospitals had >=20% of their total PCI procedures performed for unclear indications, but the proportion of FP, NFP, major teaching, and specialty hospitals reaching this threshold was not statistically different (20%, 16%, 17%, and 15%, respectively; P = .84). CONCLUSIONS: A small proportion of PCI procedures were performed in patients with unclear indications, but there was wide variation across hospitals. On average, specialty hospitals performed more PCIs for unclear indications. Efforts to reduce variability should be pursued. PMID- 22305840 TI - Percutaneous coronary intervention outcomes in US hospitals with varying structural characteristics: analysis of the NCDR(r). AB - BACKGROUND: In the United States, there continues to be debate about whether certain types of hospitals deliver improved patient outcomes. We sought to assess the association between hospital organizational characteristics and in-hospital outcomes for percutaneous coronary intervention (PCI). METHODS: Retrospective analysis of 2004 to 2007 data for 694 US hospitals participating in the CathPCI Registry((r)). Our analysis focused on 1,113,554 patients who underwent PCI in 471 not-for-profit (NFP) hospitals, 131 major teaching hospitals, 79 for-profit (FP) hospitals, and 13 physician-owned specialty hospitals. Outcomes included in hospital mortality, stroke, bleeding, vascular injury, and a composite representing one or more of the individual complications. We used the current CathPCI Registry mortality risk model to calculate risk-standardized mortality ratios (RSMRs) for each category of hospital and compared hospital groupings for all patients in aggregate and in subgroups stratified by patients' indications for PCI. RESULTS: Patients treated in major teaching hospitals were younger, whereas FP hospitals performed a greater proportion of PCI for patients with ST elevation myocardial infarction (P < .0001). Specialty hospitals treated patients with less acuity, including a lower proportion of patients with ST-elevation myocardial infarction. In unadjusted analyses, specialty hospitals had significantly lower rates of all adverse outcomes compared with NFP, teaching, and FP hospitals including in-hospital mortality (0.7%, 1.2%, 1.4%, and 1.4%, respectively; P < .001) and the composite end point (2.4%, 4.1%, 4.6%, and 4.3%, respectively; P < .001). In adjusted analyses, RSMR was significantly lower for specialty hospitals when compared with the other 3 groups for all patients in aggregate (RSMR 1.05%, 1.30%, 1.38%, 1.39%; P < .001); these differences remained clinically significant but were no longer statistically significant in subgroup analyses. CONCLUSIONS: Specialty hospitals appear to have lower rates of most adverse outcomes for PCI. Specialty hospitals may have developed expertise in narrow procedural areas that could be adapted to the larger population of general hospitals. PMID- 22305841 TI - Vascular complications and access crossover in 10,676 transradial percutaneous coronary procedures. AB - BACKGROUND: Randomized trials have shown that transradial approach, compared with transfemoral, reduces vascular complications (VCs) of coronary procedures in selected patients. Yet, radial approach is associated to a variety of access-site VC as well as to a higher failure rate compared with femoral access. METHODS: At our institution, from May 2005 to May 2010, we prospectively assessed the occurrence and outcome of VC in consecutive patients undergoing transradial percutaneous coronary procedures performed by trained radial operators. The need of access crossover to complete the procedure was also prospectively investigated. Vascular complications were classified as "radial related" or "nonradial related" (in the case of access crossover). Vascular complications were also classified "major" if requiring surgery and/or blood transfusions or causing hemoglobin drop >3 g/dL. RESULTS: Ten thousand six hundred seventy-six procedures were performed using a right radial (87.5%), left radial (12.4%), or ulnar (0.1%) artery as primary access. A total of 53 VCs (0.5%) were observed: 44 (83%) radial related and 9 (17%) nonradial related. Major VCs occurred in 16 patients only (0.2%) and were radial related in 10 (62.5%) and nonradial related in 6 (37.5%) patients. Vascular complications rate was stable during the study and independent of operator's experience. Access crossover rate was 4.9%, differed according to the operator radial experience and significantly decreased over time. CONCLUSIONS: The present study, conducted in a center with high volume of radial procedures, shows that transradial approach is associated with a very low rate of VC, which is stable over time. On the contrary, access crossover rate decreased over time and differed according to operator (radial) experience. PMID- 22305842 TI - Patient and hospital characteristics associated with traditional measures of inpatient quality of care for patients with heart failure. AB - BACKGROUND: The purpose of this study was to determine patient and hospital characteristics associated with 4 measures of quality of inpatient heart failure care used by both the primary payer of heart failure care in the United States (Center for Medicare and Medicaid Services) and the main hospital accrediting organization (The Joint Commission). METHODS: We used data from Get With The Guidelines Program for patients hospitalized with heart failure. Eligibility for receiving care based on the Center for Medicare and Medicaid Services performance measures was determined for assessment of left ventricular ejection fraction (LVEF; n = 60,601), use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) if LVEF<40% and no contraindications (24,130), discharge instructions (49,383), and smoking cessation counseling (10,152). Patient and hospital characteristics that were significantly associated with performance measures in univariate analyses were entered into multivariate logistic regression models. RESULTS: Overall, documentation for LVEF assessment was noted in 95%, ACEi/ARB use in 87%, discharge instruction in 82%, and smoking cessation counseling in 91% of eligible patients. In adjusted analyses, older patients and those with evidence of renal failure were significantly less likely to receive each care measure except for discharge instructions (no age effect). Patients with higher body mass index were more likely to receive ACEi/ARB and discharge instructions but less likely to have LVEF documented or to receive smoking cessation counseling. Small hospitals (<200 beds) were less likely to provide each of the performance measures compared with larger hospitals. CONCLUSION: Recommended heart failure care is less likely in patients with certain characteristics (older age and abnormal renal function) and those cared for in smaller hospitals. Programs to improve evidence-based care for heart failure should consider interventions specifically targeting and tailored to smaller facilities and patients who are older with comorbidities. PMID- 22305843 TI - Perceived sexual difficulties and associated factors in patients with heart failure. AB - BACKGROUND: Sexual dysfunction is a common problem of increasing incidence in patients with heart failure (HF). However, there is no knowledge on which demographic, clinical, and quality of life (QoL) aspects are related to difficulties in sexual activity nor on the course of sexual difficulties in patients with HF. METHODS: Data on sexual difficulties were collected at 1 and 18 months after an HF hospitalization (n = 792, mean age 69 +/- 12 years, 35% female, mean left ventricular ejection fraction 33% +/- 14%) by the question on sexuality of the Minnesota living with HF questionnaire. Demographic and clinical factors were assessed from medical records and QoL by Minnesota living with HF questionnaire, Medical Outcome Study 36-item General Health Survey, and Ladder of Life. RESULTS: In total, 48% (n = 380) of the patients perceive difficulties in sexual activity at 1 month after discharge, and 70% continued to perceive this at 18 months. Furthermore, 27% of the patients without difficulties at 1 month developed them during follow-up. Living with a partner (OR 3.76, 95% CI 2.58 5.48), younger age (OR 0.96, 95% CI 0.94-0.97)), male gender (OR 3.08, 95% CI 2.10-4.43), overall well-being (OR 1.13, 95% CI 1.00-1.27), and physical (OR 1.06, 95% CI 1.06-1.08) and emotional (OR 1.07, 95% CI 1.03-1.10) QoL were independently associated with perceived difficulties in sexual activity. CONCLUSIONS: Perceived difficulties in sexual activity are common in patients with HF, particularly in younger and male patients and continue over time. Patients who perceive difficulties in sexual activity report a significant lower QoL and overall well-being than those who do not. PMID- 22305844 TI - Comparison of processes of care and clinical outcomes for patients newly hospitalized for heart failure attended by different physician specialists. AB - BACKGROUND: Previous studies suggest that patients with heart failure (HF) treated by cardiologists have improved outcomes compared with patients treated by other physicians. It remains unclear whether these findings reflect differences in patient characteristics, processes of care, practice setting, or a combination of these factors. METHODS: We examined physician specialty-related differences in processes of care and clinical outcomes for 7,634 patients newly hospitalized for HF in Ontario, Canada, who were included in the EFFECT study between April 2004 and March 2005. Patients were categorized according to whether they received cardiologist, generalist (e.g., internist or family doctor), or generalist care with cardiology consultation. RESULTS: Multivariable hierarchical modeling demonstrated that patients treated by generalists alone had higher risk of 30-day (odds ratio [OR] 1.50, 95% CI 1.18-1.91) and 1-year mortality (OR 1.29, 95% CI 1.10-1.50), as well as the 1-year composite outcome of death and readmission, compared with patients treated by cardiologists. These differences were significantly attenuated if patients who had "do not resuscitate" orders were excluded. Patients who had a cardiologist involved in their care were more likely to undergo diagnostic procedures, such as echocardiography, and had higher rates of certain evidence-based pharmacologic therapy such as beta-blockers. CONCLUSION: Physician specialty-related differences in HF outcomes appear to reflect a combination of both case-mix differences and differences in the use of certain heart failure processes of care. These findings suggest that it may be possible to improve HF outcomes in patients receiving care from generalist physicians. PMID- 22305845 TI - Effect of QRS morphology on clinical event reduction with cardiac resynchronization therapy: meta-analysis of randomized controlled trials. AB - BACKGROUND: Cardiac resynchronization therapy (CRT) is effective in reducing clinical events in systolic heart failure patients with a wide QRS. Previous retrospective studies suggest only patients with QRS prolongation due to a left bundle-branch block (LBBB) benefit from CRT. Our objective was to examine this by performing a meta-analysis of all randomized controlled trials of CRT. METHODS: Systematic searches of MEDLINE and the Food and Drug Administration official website were conducted for randomized controlled CRT trials. Trials reporting adverse clinical events (eg, all-cause mortality, heart failure hospitalizations) according to QRS morphology were included in the meta-analysis. RESULTS: Four randomized trials totaling 5,356 patients met the inclusion criteria. In patients with LBBB at baseline, there was a highly significant reduction in composite adverse clinical events with CRT (RR = 0.64 [95% CI (0.52-0.77)], P = .00001). However no such benefit was observed for patients with non-LBBB conduction abnormalities (RR = 0.97 [95% CI (0.82-1.15)], P = .75). When examined separately, there was no benefit in patients with right-bundle branch block (RR = 0.91 [95% CI (0.69-1.20)], P = .49) or non-specific intraventricular conduction delay (RR = 1.19 [95% CI (0.87-1.63)], P = .28). There was no heterogeneity among the clinical trials with regards to the lack of benefit in non-LBBB patients (I(2) = 0%). When directly compared, the difference in effect of CRT between LBBB versus non-LBBB patients was highly statistically significant (P = .0001 by heterogeneity analysis). CONCLUSIONS: While CRT was very effective in reducing clinical events in patients with LBBB, it did not reduce such events in patients with wide QRS due to other conduction abnormalities. PMID- 22305846 TI - Frequency and impact of lifestyle modification in patients with coronary artery disease: the Japanese Coronary Artery Disease (JCAD) study. AB - BACKGROUND: Lifestyle modifications such as exercise and diet interventions in patients with coronary artery disease (CAD) are widely regarded as important, but little is known about their frequency in clinical practice and their impact on all-cause mortality. METHODS: The JCAD study is a cohort study of 13,812 patients with CAD (>=75% stenosis in >=1 of 3 major coronary arteries). Patients were enrolled from April 2000 through March 2001 at 202 institutions throughout Japan. Exercise and diet interventions were defined based on Japanese national guidelines. Cox proportional hazards models were used to calculate hazard ratios (HRs) for all-cause mortality with 95% CIs. RESULTS: We studied 11,893 patients in the JCAD study. Over 3 years of follow-up, there were 474 deaths; 4,237 patients (35.6%) underwent exercise intervention, and 8,642 patients (72.7%) underwent diet intervention from the time of discharge. Mortality was lower in patients who underwent an exercise or diet intervention than in patients who did not: HR 0.68 (95% CI 0.56-0.84) and 0.75 (95% CI 0.62-0.91), respectively. After adjustment for age, sex, institution, hypertension, hyperlipidemia, diabetes, obesity, current drinking, current smoking, and the use of antiplatelet agents, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and statins, the associations with these interventions remain statistically significant: HR 0.73 (95% CI 0.55-0.96) for exercise and 0.74 (95% CI 0.58-0.95) for diet interventions. CONCLUSIONS: Exercise and diet interventions have a beneficial impact on all-cause mortality in patients with CAD, yet these interventions are surprisingly infrequent. Lifestyle interventions should be more actively promoted. PMID- 22305848 TI - Cardiopulmonary exercise function among patients undergoing transcatheter pulmonary valve implantation in the US Melody valve investigational trial. AB - OBJECTIVES: We assessed the hypothesis that there is an improvement in clinical and physiologic parameters of cardiopulmonary exercise testing (CPET) after implantation of a transcatheter pulmonary valve (TPV). BACKGROUND: Transcatheter pulmonary valve provides a new tool for treating conduit stenosis and regurgitation in patients with right ventricle (RV) to pulmonary artery conduit dysfunction. METHODS: Patients who underwent a TPV placement between January 2007 and January 2010 (N = 150) were investigated with a standardized CPET protocol before and at 6 months after TPV placement. Cardiopulmonary exercise testing was performed on a mechanically braked cycle ergometer with respiratory gas exchange analysis. RESULTS: Six months post TPV, small but statistically significant improvements were observed in the maximum workload (65.0% +/- 18.8% to 68.3% +/- 20.3% predicted, P < .001) and the ratio of minute ventilation to CO(2) production at the anaerobic threshold (30.8 +/- 4.7 to 29.1 +/- 4.1, P < .001). There was no significant change in peak oxygen consumption (VO(2)). Patients with pre-TPV hemodynamics consistent with RV dysfunction and patients with a lower pre TPV peak VO(2) tended to have the greatest improvement in peak VO(2). The correlation between TPV-related improvements in peak VO(2) and baseline clinical variables were weak, however, and these variables could not be used to reliably identify patients likely to have improved peak VO(2) after TPV. CONCLUSION: In patients with RV to pulmonary artery conduit dysfunction, TPV is associated with modest improvement in exercise capacity and gas exchange efficiency during exercise. PMID- 22305847 TI - Associations of pentraxin-3 with cardiovascular events, incident heart failure, and mortality among persons with coronary heart disease: data from the Heart and Soul Study. AB - BACKGROUND: Pentraxin-3 (PTX3) is an inflammatory marker thought to be more specific to vascular inflammation than C-reactive protein (CRP). Whether PTX3 is independently associated with adverse events among persons with stable coronary heart disease (CHD), independently of CRP, and whether kidney dysfunction influences these associations are not known. METHODS: We evaluated the associations of baseline PTX3 levels with all-cause mortality, cardiovascular (CV) events (myocardial infarction, stroke, or CHD death), and incident heart failure (HF) during 37 months among ambulatory persons with stable CHD participating in the Heart and Soul Study. Cox proportional hazards models were adjusted for age, sex, race, hypertension, diabetes, smoking, and CRP. RESULTS: Among 986 persons with stable CHD, each 1 unit increase in log PTX3 at baseline was associated with an 80% increased risk of all-cause mortality (hazard ratio [HR] 1.8, 95% CI 1.5-2.1), a 50% increased risk of CV events (HR 1.5, 95% CI, 1.2 1.9), and an 80% greater risk of incident HF (HR 1.8, 95% CI, 1.3-2.5). Further adjustment for estimated glomerular filtration rate (eGFR) attenuated these associations to 1.6 (1.3-1.9) for mortality, 1.3 (1.0-1.6) for CV events and 1.5 (1.1-2.1) for incident HF. Stratification by eGFR >60 mL/min per 1.73m(2) or <60 mL/min per 1.73m(2) did not affect these associations (P interaction > .3 for all outcomes). CONCLUSIONS: Among persons with stable CHD, higher PTX3 concentrations were associated with increased risk for all-cause mortality, CV events, and incident HF independently of systemic inflammation. Adjustment for eGFR modestly attenuated these associations, suggesting that future studies of PTX3 should adjust for kidney function. PMID- 22305849 TI - Survival and predictive factors of mortality after 30 days in patients treated with percutaneous implantation of the CoreValve aortic prosthesis. AB - BACKGROUND: Few data exist on the clinical impact of transcatheter aortic valve implantation (TAVI) in patients with symptomatic aortic stenosis and a high surgical risk. The aim of this study was to determine the survival and the factors predicting mortality after 30 days post-TAVI with the CoreValve prosthesis (Medtronic, Minneapolis, MN). METHODS: From April 2008 to October 2010, the CoreValve prosthesis (Medtronic) was implanted in 133 consecutive high risk surgical patients with symptomatic severe aortic stenosis. RESULTS: The mean age was 79.5 +/- 6.7 years. The logistic European System for Cardiac Operative Risk Evaluation was 21.5% +/- 14%. The implantation success rate was 97.7%. In hospital mortality was 4.5%, and the combined end point of death, vascular complications, myocardial infarction, or stroke had a rate of 9%. Survival at 12 and 24 months was 84.5% and 79%, respectively, after a mean follow-up of 11.3 +/- 8 months. The New York Heart Association functional class improved from 3.3 +/- 0.5 to 1.18 +/- 0.4 and remained stable at 1 year. A high Charlson index (hazard ratio [HR] 1.44, 95% CI 1.09-1.89, P < .01) and a worse Karnofsky score before the procedure (HR 0.95, 95% CI 0.92-0.99, P = .021) were predictors of mortality after 30 days. CONCLUSIONS: Transcatheter aortic valve implantation with the CoreValve prosthesis for patients with aortic stenosis and a high surgical risk is a safe, efficient option resulting in a medium-term clinical improvement. Survival during follow-up depends on the associated comorbidities. Early mortality beyond 30 days is predicted by preoperative comorbidity scores and the functional status of the patient. PMID- 22305850 TI - Aggregating traditional cardiovascular disease risk factors to assess the cardiometabolic health of childhood cancer survivors: an analysis from the Cardiac Risk Factors in Childhood Cancer Survivors Study. AB - BACKGROUND: Childhood cancer survivors are at increased risk of cardiovascular disease (CVD), which may be associated with traditional CVD risk factors. We used CVD risk aggregation instruments to describe survivor cardiometabolic health and compared their results with sibling controls. METHODS: Traditional CVD risk factors measured in 110 survivors and 31 sibling controls between 15 and 39 years old were aggregated using Pathobiological Determinants of Atherosclerosis in Youth (PDAY) scores and the Framingham Risk Calculator (FRC) and expressed as ratios. The PDAY odds ratio represents the increased odds of currently having an advanced coronary artery lesion, and the FRC risk ratio represents the increased risk of having a myocardial infarction, stroke, or coronary death in the next 30 years. Ratios are relative to an individual of similar age and sex without CVD risk factors. RESULTS: The median PDAY odds ratio for survivors was 2.2 (interquartile range 1.3-3.3), with 17% >4. The median FRC risk ratio was 1.7 (interquartile range 1.0-2.0), with 12% >4. Survivors and siblings had similar mean PDAY odds ratios (2.33 vs 2.29, P = .86) and FRC risk ratios (1.72 vs 1.53, P = .24). Cancer type and treatments were not associated with cardiometabolic health. There was a suggested association for physical inactivity with PDAY odds ratios (r = 0.17, P = .10) and FRC risk ratios (r = 0.19, P = .12). CONCLUSIONS: Cardiometabolic health is poor in childhood cancer survivors but not different than that of their siblings, highlighting the importance of managing traditional CVD risk factors and considering novel exposures in survivors. PMID- 22305851 TI - Obesity and physical fitness in California school children. AB - BACKGROUND: Obesity rates have reached epidemic proportions in the United States and California. Thus, the California Department of Education began a series of steps to address the increase in obesity and decline in fitness in the 6.3 million public school children in California. We evaluated serial changes in obesity and fitness in California school children following implementation of prevention steps in all California public schools. METHODS: The California Department of Education implemented changes in school nutrition and exercise programs aimed at reducing obesity and improving fitness. Outcome results were monitored by performing Physical Fitness Testing on 8.4 million students (5th, 7th, and 9th grade) for body composition, aerobic capacity, flexibility, and upper body, abdominal, and truncal strength using the Cochran-Armitage trend test and multivariable logistic regression models. RESULTS: Overall fitness improved from 2003 to 2008. Serial changes in body composition, aerobic capacity, flexibility, and upper body, abdominal, and truncal strength improved or remained stable within school as students progressed from 5th to 7th to 9th grade. However, students entering 5th grade were more obese every year, and this early obesity was not reversible within the school programs. CONCLUSIONS: Following prevention measures within California public schools, obesity and fitness levels have stabilized. However, continued increases in early entrance (5th grade) obesity will require additional efforts directed at preschool and elementary students to completely stop and reverse this obesity epidemic. PMID- 22305852 TI - The consequences of risk-based surveillance: Developing output-based standards for surveillance to demonstrate freedom from disease. AB - Output-based surveillance standards provide a mechanism to achieve harmonised and comparable surveillance (which meets a defined objective) while allowing flexible approaches that are adapted to the different populations under surveillance. When correctly implemented, they can result in lower cost and greater protection against disease spread. This paper presents examples of how risk-based sampling can improve the efficiency of surveillance, and describes the evolution of output based surveillance standards for demonstration of freedom from disease in terms of three generations of approach: surveillance sensitivity, probability of freedom, and expected cost of error. These three approaches progressively capture more of the factors affecting the final outcome. The first two are relatively well accepted but the third is new and relates to the consequences of infection. There has been an increased recognition of the value of risk-based sampling for demonstration of freedom from disease over the last decades, but there has been some disagreement about practical definitions and implementation, in particular as to whether 'risk-based' implies probability of infection or probability and consequences. This paper argues that risk-based sampling should be based solely on the probability of infection of a unit within the population, while the consequences of infection should be used to set the target probability of freedom. This approach provides a quantitative framework for planning surveillance which is intuitively understandable. The best way to find disease, if it is present, is to focus on those units that are most likely to be infected. However, if the purpose of surveillance includes mitigating the risk of a disease outbreak, we want to ensure that that risk is smallest in those populations where the consequences of failure to detect are greatest. PMID- 22305853 TI - A practical framework for conducting Foreign Animal Disease surveillance. AB - This manuscript was written in honour of Dr. Preben Willeberg to illustrate some tools that may be useful to "make surveillance happen" and to build bridges between science and application in animal health surveillance. The paper illustrates how four elements (science, project management, communication and documentation) may be combined with some tools into a practical framework for Foreign Animal Disease surveillance. Specifically, I will show how the four elements are essential to make surveillance happen and provide a link between science and application in animal health surveillance. The Canadian Notifiable Avian Influenza Surveillance system is used as an example. In surveillance for Foreign Animal Diseases (FAD), with veterinary authorities as the lead and with many stakeholders, project management can support science in building evidence (documentation) that can be delivered (communicated) to trade negotiators and international trade partners. To bridge the gap between science and application in FAD surveillance I propose that we need people with skills in science, project management, communication and documentation. PMID- 22305854 TI - Fabry disease: biochemical, pathological and structural studies of the alpha galactosidase A with E66Q amino acid substitution. AB - Recently, male subjects harboring the c.196G>C nucleotide change which leads to the E66Q enzyme having low alpha-galactosidase A (GLA) activity have been identified at an unexpectedly high frequency on Japanese and Korean screening for Fabry disease involving dry blood spots and plasma/serum samples. Individuals with the E66Q enzyme have been suspected to have the later-onset Fabry disease phenotype leading to renal and cardiac disease. However, there has been no convincing evidence for this. To determine whether c.196G>C (E66Q) is disease causing or not, we performed biochemical, pathological and structural studies. It was predicted that the E66Q amino acid substitution causes a small conformational change on the molecular surface of GLA, which leads to instability of the enzyme protein. However, biochemical studies revealed that subjects harboring the E66Q enzyme exhibited relatively high residual enzyme activity in white blood cells, and that there was no accumulation of globotriaosylceramide in cultured fibroblasts or an increased level of plasma globotriaosylsphingosine in these subjects. An electron microscopic examination did not reveal any pathological changes specific to Fabry disease in biopsied skin tissues from a male subject with the E66Q enzyme. These results strongly suggest that the c.196G>C is not a pathogenic mutation but is a functional polymorphism. PMID- 22305855 TI - Atypical pyridoxine-dependent epilepsy due to a pseudoexon in ALDH7A1. AB - We report two siblings with atypical pyridoxine-dependant epilepsy, modest elevation of biomarkers, in which the open reading frame and the splice sites of ALDH7A1 did not show any mutations. Subsequent genetic analysis revealed a deep homozygous intronic mutation in ALDH7A1 resulting in two types of transcripts: the major transcript containing a pseudoexon, and the minor transcript representing the authentic spliced transcript. In future, this mutation may be targeted with antisense-therapy aiming at exclusion of the pseudoexon. PMID- 22305856 TI - The use of parenteral nutrition for the management of PKU patient undergoing chemotherapy for lymphoma: a case report. AB - The metabolic control of phenylalanine levels is a challenge during illness. We present the metabolic management of a 6 year old boy with classical PKU who was diagnosed with stage III intraabdominal Burkit's lymphoma and underwent surgical resection and chemotherapy. The metabolic control during chemotherapy was achieved by the use of parenteral custom made amino acid solution and pro-active adjustment of intake. From the 94 obtained plasma phenylalanine (Phe) levels, 18.4% were above our clinic's recommended upper limit (360 MUmol/L, 6 mg/dL) while 52.7% of Phe levels were below the recommended lower limit (120 MUmol/L, 2 mg/dL). Phe levels above recommended range were associated with low caloric/protein intake, while levels below recommended range reflected the difficulty in achieving the full prescribed Phe intake. We recommend early institution of custom made amino acid solution with maximum amino acid content and caloric intake to provide optimal phenylalanine control. Administration of phenylalanine via regular intravenous amino acid solution may assist in avoiding low Phe levels when prescribed intake is compromised due to vomiting and other disease related illnesses. Use of custom made, phenylalanine free amino acid solution proved beneficial in the management of blood phenylalanine levels in a PKU patient during chemotherapy for Burkitt lymphoma. PMID- 22305857 TI - Engineering of ribozyme-based riboswitches for mammalian cells. AB - Artificial RNA riboswitches--apart from protein-based gene regulation systems, which have been known about for a long time--have become increasingly important in biotechnology and synthetic biology. Aptamer-controlled hammerhead ribozymes (so-called aptazymes) have been shown to be a versatile platform for the engineering of novel gene regulators. Since aptazymes are cis-acting elements that are located in the untranslated regions of a gene of interest, their application does not need any further protein co-factor. This presents the opportunity to simplify complex gene networks while simultaneously expanding the repertoire of available parts. Nevertheless, the generation of novel aptazymes requires a functional aptamer-ribozyme connection, which can be difficult to engineer. This article describes a novel approach for using fluorescence activated cell sorting (FACS) in order to identify functional aptazymes in bacteria and their subsequent transfer into mammalian cells. PMID- 22305858 TI - Sebaceous gland metaplasia in the oesophagus of a cynomolgus monkey (Macaca fascicularis). AB - Microscopical evaluation of tissues from a mature female cynomolgus monkey assigned to a 13-week oral toxicity study revealed nests of sebaceous cells within the mucosa of the distal oesophagus. The sebaceous cell nests showed normal differentiation from basally-oriented seboblasts to centrally-orientated mature sebocytes. No excretory ducts were found, but solitary or small groups of vacuolated sebocytes were present in the overlying normal, non-keratinized squamous epithelium. The finding of sebaceous cells, of presumed ectodermal origin, in the oesophageal mucosa, which is of endodermal origin, is of scientific interest. Different theories may explain the existence of this peculiarity, but sebaceous gland metaplasia is the most plausible. The mucosal change was thought to be unrelated to treatment and is the first case of sebaceous gland metaplasia reported in the oesophagus of a non-human primate. PMID- 22305859 TI - Differences between dialysis modality selection and initiation. AB - BACKGROUND: Although dialysis modality education is associated with higher rates of peritoneal dialysis (PD) use, some patients start hemodialysis (HD) therapy despite initially selecting PD as their modality of choice. This study seeks to identify predictors of this discrepancy. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 217 patients who received dialysis modality education at the University of Rochester between January 2004 and September 2009 and subsequently started dialysis therapy. PREDICTORS: Demographic (age, race, sex, and timing of education), social (education, income, insurance, marital, employment, and smoking status), and clinical data (estimated glomerular filtration rate, cause of end-stage renal disease [ESRD], number of comorbid conditions, and number of nephrology visits). OUTCOME: HD use at initiation and day 91 of dialysis therapy in patients initially selecting PD. RESULTS: Of 217 patients receiving education and starting dialysis therapy, at the time of education, 124 chose PD, 52 were undecided, and 41 chose HD. Modality distribution at the time of dialysis therapy initiation was 150 with HD and 67 with PD. Of 124 patients who chose PD at the time of education, 59 started dialysis therapy with PD and 65 started with HD. On day 91, a total of 60 patients were on PD therapy and 55 were on HD therapy. Nine patients had either died, undergone transplant, or not yet reached 91 days of dialysis therapy. On multivariable analysis, nonglomerular cause of ESRD, age older than 75 years, and not being employed predicted starting with HD therapy, whereas age older than 75 years, nonwhite race, and nonglomerular cause of ESRD predicted HD use at day 91. LIMITATIONS: Single-center observational study. CONCLUSIONS: This study shows that patients choosing PD after dialysis education may not start with this modality and identifies several predictors of this mismatch. Further investigation into predictors of this discrepancy and strategies promoting a PD start in patients selecting this modality are warranted. PMID- 22305860 TI - Nesiritide ASCENDs the ranks of unproven treatments for acute heart failure. PMID- 22305861 TI - Amyloid precursor protein is a biomarker for transformed human pluripotent stem cells. AB - Increasing evidence suggests an important function of the beta-amyloid precursor protein (APP) in malignant disease in humans; however, the biological basis for this evidence is not well understood at present. To understand the role of APP in transformed pluripotent stem cells, we studied its expression levels in human testicular germ cell tumors using patient tissues, model cell lines, and an established xenograft mouse model. In the present study, we demonstrate the cooperative expression of APP with prominent pluripotency-related genes such as Sox2, NANOG, and POU5F1 (Oct3/4). The closest homologue family member, APLP2, showed no correlation to these stem cell factors. In addition, treatment with histone deacetylase (HDAC) inhibitors suppressed the levels of APP and stem cell markers. Loss of pluripotency, either spontaneously or as a consequence of treatment with an HDAC inhibitor, was accompanied by decreased APP protein levels both in vitro and in vivo. These observations suggest that APP represents a novel and specific biomarker in human transformed pluripotent stem cells that can be selectively modulated by HDAC inhibitors. PMID- 22305862 TI - [Pelvi-abdominal hematoma: a five years study]. AB - OBJECTIVES: To investigate the incidence of pelvi-abdominal hematoma, to identify associated factors and to describe modalities of diagnosis and management. PATIENTS AND METHODS: A retrospective observational study including all patients presenting with a pelvi-abdominal hematoma among women who delivered between January 2005 and December 2010 in Toulouse university hospital. RESULTS: Twenty five thousand, one hundred and eighty-four women delivered during the study period and nine women were included (estimated incidence: 1/4200 deliveries). The main associated obstetrical factors were perineal injuries (episiotomy or lacerations) in 100% of cases and instrumental extraction (spatula) in 50% of cases. Arterial embolisation was performed in one third of cases. No death was observed. CONCLUSION: Pelvi-abdominal hematoma is a severe and infrequent postpartum complication. A better knowledge of clinical and radiological presentations together with obstetrical associated factors will allow an early diagnosis and a multidisciplinary management. PMID- 22305863 TI - Technical and clinical long-term results of infrapopliteal percutaneous transluminal angioplasty for critical limb ischemia. AB - PURPOSE: To evaluate the technical success and clinical long-term effectiveness of percutaneous transluminal angioplasty (PTA) of the infrapopliteal arteries in critical limb ischemia (CLI) and to determine if total vessel dilation (TVD) increases the limb salvage rate (LSR). MATERIALS AND METHODS: A retrospective study was performed in 90 consecutive patients (35 men and 55 women, median age 79 years, standard deviation [SD] 9 years) over a 5.5-year period to determine the effectiveness of infrapopliteal PTA in treating CLI. Of 90 patients, 61 underwent TVD. Analysis of LSR was performed using the Kaplan-Meier life-table analysis. RESULTS: In 90 limbs, there were 57 infrapopliteal stenoses and 104 occlusions. Including 10 technical failures (TF) (TF = 11%), LSR at 1 year and 3 years for all 90 patients with previously untreated lesions was 78%. For 80 technically successful (TS) procedures (TS = 89%), LSR at 1 year and 3 years was 87%. At 1 year and 3 years, LSR for the 61 patients who had TVD was 89%. In all patients, there were no amputations after the first year. The 30-day mortality rate was 7%. CONCLUSIONS: PTA of the infrapopliteal arteries appears to be an effective treatment for patients with CLI. TVD provides an improved LSR and warrants additional evaluation. PMID- 22305864 TI - Vascular surgery collaboration during pancreaticoduodenectomy with vascular reconstruction. AB - BACKGROUND: Once thought to have unresectable disease, pancreatic cancer patients with portal venous involvement are now reported to have comparable survival after pancreaticoduodenectomy (PD) with vascular reconstruction (VR) as compared with patients without vascular involvement. We hypothesize that a multidisciplinary approach involving a vascular surgeon will minimize morbidity and improve patency of VRs. METHODS: We identified 204 patients who underwent PD for pancreatic adenocarcinoma from 1997 to 2008. Patients who underwent PD with VR (N = 42) were compared with those who underwent standard PD (N = 162). VRs were performed by a vascular surgeon and involved primary repair (N = 8), vein patch (N = 25), or interposition grafting (N = 9) with femoral or other venous conduit. RESULTS: Patients undergoing PD with VR had larger tumors (3.0 cm vs. 2.5 cm, P < 0.01) but did not have different rates of tumor-free margins (73% vs. 72%, P = 0.84) or lymph nodes metastases (50% vs. 38%, P = 0.14). The VR group had higher median blood loss (875 mL vs. 550 mL, P = 0<0.01), but no differences in mortality, complication rates, length of stay, or readmission rates were found in a median follow-up of 29 months. Overall survival rates were similar. Predictors of mortality on multivariate analysis included increasing histological grade (P = 0.01), positive lymph nodes (P = 0.01), and increasing tumor size (P = 0.01), but not VR (P = 0.28). When evaluated by computed tomography scans within 6 months postoperatively, 97% of reconstructions remained patent. CONCLUSIONS: The need for VR is not a contraindication to potentially curative resection in patients with pancreatic adenocarcinoma. Assistance of a vascular surgeon during VR may allow moderate-volume centers to achieve outcomes comparable with high-volume centers. PMID- 22305865 TI - Intraluminal thrombus has a selective influence on matrix metalloproteinases and their inhibitors (tissue inhibitors of matrix metalloproteinases) in the wall of abdominal aortic aneurysms. AB - BACKGROUND: The influence of intraluminal thrombus (ILT) on the proteolytic environment within the wall of an abdominal aortic aneurysm (AAA) is unknown. This is the first study to examine the correlation between ILT thickness and the levels of matrix metalloproteinases (MMPs) and their natural inhibitors (tissue inhibitors of matrix metalloproteinases [TIMPs]) within the adjacent AAA wall. METHODS: Thirty-five patients undergoing elective repair of AAAs were studied. A single full-thickness infrarenal aortic sample was obtained uniformly from the arteriotomy site from each patient. All samples were snap frozen and analyzed for total and active MMP 2, 8, and 9 and TIMP 1 and 2. Thrombus thickness at the specimen site was measured on the preoperative contrast computed tomographic angiograms. RESULTS: There was a statistically significant correlation between ILT thickness, concentration of TIMP 1, and active concentration of MMP 9. MMP 2 (active and total) and TIMP 2 demonstrated a positive correlation with ILT thickness, although not statistically significant. CONCLUSION: In this novel study, we found a significant positive correlation of ILT thickness with active MMP 9 and TIMP 1 concentration in the adjacent AAA wall, and this may have implications for AAA expansion and eventual rupture. PMID- 22305866 TI - Attention-deficit/hyperactivity disorder comorbidity in a sample of veterans with posttraumatic stress disorder. AB - This study examined attention-deficit/hyperactivity disorder (ADHD) comorbidity in military veterans with a high prevalence of posttraumatic stress disorder (PTSD) and evaluated the relationships between the 2 disorders and exposure to traumatic events. The sample included 222 male and female military veterans who were administered structured clinical interviews based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Results show that 54.5% met the criteria for current PTSD, 11.5% of whom also met the criteria for current adult ADHD. Level of trauma exposure and ADHD severity were significant predictors of current PTSD severity. Evaluation of the underlying structure of symptoms of PTSD and ADHD using confirmatory factor analysis yielded a best fitting measurement model that comprised 4 PTSD factors and 3 ADHD factors. Standardized estimates of the correlations among PTSD and ADHD factors suggested that the largest proportion of shared variance underlying PTSD-ADHD comorbidity is related to problems with modulating arousal levels that are common to both disorders (ie, hyperarousal and hypoarousal). PMID- 22305867 TI - Different expression patterns of PRRSV mediator genes in the lung tissues of PRRSV resistant and susceptible pigs. AB - Porcine reproductive and respiratory syndrome (PRRS) has caused severe economic loss in most swine-producing countries. The resistance to PRRS virus (PRRSV) infection varies among pig breeds and lines. In this study, we found that the Chinese Dapulian pigs (DPL) were more resistant to PRRSV than commercial Duroc*Landrace*Yorkshire (DLY) crossbred pigs in that lower rectal temperature and lower PRRSV copy number in the serum were detected in the former. Analysis of the mRNA expression of five PRRSV mediator genes (SIGLEC1, NMMHC-IIA, CD163, VIM and HSPG2) in the lung tissues indicated differences in expression between DLY and DPL pigs. In uninfected porcine lung tissues, the levels of SIGLEC1, NMMHC IIA, CD163 and VIM genes were significantly higher in DLY than in DPL pigs (P<0.05); in PRRSV-infected pigs, the expression levels of NMMHC-IIA and CD163 mRNA were significantly higher in DPL pigs compared to uninfected ones (P<0.05), whereas these levels were not different in DLY pigs or between infected DPL and DLY pigs. Thus, the different expression of PRRSV mediator genes is likely related to pig resistance to PRRSV. PMID- 22305868 TI - A hollow cylindrical nano-hydroxyapatite/polyamide composite strut for cervical reconstruction after cervical corpectomy. AB - This retrospective study included 35 patients who had a nano hydroxyapatite/polyamide (n-HA/PA) composite strut implanted for cervical reconstruction and fusion after corpectomy from 2006 to 2008. The average follow up period was 38.5 months (range: 24-48 months). The Japanese Orthopedic Association score and visual analog pain scale score were significantly improved and maintained to the last follow-up. The cervical curvature and the height of fused segments were also corrected significantly and retained to the last follow up. A total of 94.3% of patients had achieved radiographic bony fusion at the postoperative 24-month follow-up. One patient presented with subsidence of the n HA/PA composite strut and dislodgement of the screws, but the patient had no discomfort and no additional surgery was needed. We conclude that the n-HA/PA composite strut is scientifically and technically sound for cervical reconstruction and interbody fusion after corpectomy with anterior plate fixation. PMID- 22305869 TI - Three-dimensional anatomical accuracy of cranial models created by rapid prototyping techniques validated using a neuronavigation station. AB - In neurosurgery and ear, nose and throat surgery the application of computerised navigation systems for guiding operations has been expanding rapidly. However, suitable models to train surgeons in using navigation systems are not yet available. We have developed a technique using an industrial, rapid prototyping process from which accurate spatial models of the cranium, its contents and pathology can be reproduced for teaching. We were able to register, validate and navigate using these models with common available navigation systems such as the Medtronic StealthStation S7(r). PMID- 22305870 TI - Indirect compressive injury to the inferior alveolar nerve caused by dental implant placement. PMID- 22305871 TI - beta-Thalassemia: medical and surgical considerations in managing facial deformities: case report and review of the literature. PMID- 22305872 TI - Logistic regression analysis of risk factors for the development of alveolar osteitis. AB - PURPOSE: To assess risk factors for alveolar osteitis. MATERIALS AND METHODS: A prospective nested case-control study was conducted in an urban community dental clinic in Valdivia, Chile. A cohort of 1,355 patients who underwent dental extractions was included. Eight predictor variables (risk factors), namely patient gender, hygiene, tooth location, previous surgical site infection, traumatic extraction, systemic diseases, alcohol consumption, and tobacco use, were considered in a risk factor model. A binary regression logistic analysis was performed to determine significant associations. RESULTS: In total 1,302 participants completed the follow-up. Eighty incident case patients with alveolar osteitis and 80 matched control patients were included. A statistically significant association was found between traumatic extraction (odds ratio [OR], 13.1; 95% confidence interval [CI], 5.4 to 31.7), tobacco smoking after extraction (OR, 3.5; 95% CI, 1.3 to 9.0), previous surgical site infection (OR, 3.3; 95% CI, 1.4 to 7.7), and the development of alveolar osteitis. CONCLUSIONS: Previous surgical site infection, traumatic extraction, and tobacco smoking are associated with an increased risk of alveolar osteitis. PMID- 22305873 TI - Intraoral multifocal and multinodular adult rhabdomyoma: report of a case. PMID- 22305874 TI - Extensive gingival hemangioma in a 10-year-old boy treated by sclerotherapy: a case report. PMID- 22305875 TI - Segmental distraction osteogenesis of the anterior alveolar process using tooth borne devices: is it skeletal movement or mainly dental tipping? AB - PURPOSE: Segmental distraction osteogenesis of the anterior alveolar process has been introduced as a technique designed to avoid extractions in patients with severe dental crowding. The aim of this study was to quantify the degree of dental tipping within the alveolar segment after distraction osteogenesis. PATIENTS AND METHODS: Patients treated for dental crowding, retruded anterior alveolar process, or flat curves of Spee using segmental distraction osteogenesis of the anterior alveolar process were included in the study. Dental-borne distraction devices were used while measuring points, and angles were defined to analyze the amount of dental tipping of the lower incisors after distraction. The measurements were performed using cone-beam computed tomographic scans. Periodontal health (eg, gingival recession, tooth mobility, and dental socket depths) was evaluated after distraction. A descriptive statistical analysis was performed. RESULTS: Fifteen patients were included in the study. The amount of dental tipping within the total movement of the alveolar process showed a mean of 24% after distraction osteogenesis, whereas the skeletal movement was 76%. Dental socket depths and tooth mobility remained at the same levels as those before distraction osteogenesis. In one third of patients, gingival recession was observed around the canines. CONCLUSIONS: Segmental distraction osteogenesis of the anterior process is a powerful technique that can prevent extractions in patients with dental crowding. The technique can also compensate for retruded anterior alveolar process and accelerate or decelerate the curve of Spee. Patients with constricted periodontal health and those with a thin mandibular symphysis, however, cannot be treated with this technique because of the increased risk of dental tipping. Severe gingival recession must also be considered a possible side effect associated with this technique. PMID- 22305876 TI - Seroprevalence and risk factors for Toxoplasma gondii infection in domestic cats in The Netherlands. AB - Cats, as definitive hosts, play an important role in the transmission of Toxoplasma gondii. To determine the seroprevalence and risk factors for T. gondii infection in Dutch domestic cats, serum samples of 450 cats were tested for T. gondii antibodies by indirect ELISA. Binary mixture analysis was used to estimate the seroprevalence, the optimal cut-off value and the probability of being positive for each cat. The seroprevalence was estimated at 18.2% (95% CI: 16.6 20.0%) and showed a decrease with age in very young cats, an increase up to about 4 years old and ranged between 20 and 30% thereafter. Hunting (OR 4.1), presence of a dog in the household (OR 2.1), former stray cat (OR 3.3) and feeding of raw meat (OR 2.7) were identified as risk factors by multivariable logistic regression analysis. Prevalence differences were estimated by linear regression on the probabilities of being positive and used to calculate the population attributable fractions for each risk factor. Hunting contributed most to the T. gondii seroprevalence in the sampled population (35%). PMID- 22305877 TI - Impact of baiting on feral swine behavior in the presence of culling activities. AB - We studied the effects of baiting on feral swine (Sus scrofa) movements and corresponding likelihood of disease spread under real and simulated culling pressure. Our objectives were to determine the proportion of feral swine that used the bait station site, and if baiting of feral swine altered areas of utilization, distances from location centroids to treatment location (control or bait station), and movement rates by survivors during culling activities. We hypothesized that the bait station would increase the sedentary nature of feral swine, thus reducing the potential for dispersal and hence disease dispersal. Our experiment was conducted between February and May 2011 on the Rob and Bessie Welder Wildlife Foundation (WWF) in San Patricio County, Texas. We trapped 83 feral swine and placed GPS collars on 21 animals. We established and maintained a centralized bait station on one side of the WWF from 13 March to 27 April. We conducted population-wide culling activities, including trapping, controlled shooting, drive shooting, and aerial gunning, from 3 to 27 April and removed 143 feral swine (4.6feral swine/km(2)). Areas of utilization did not differ between treatments (control or bait station). However, we found location centroids of bait station site feral swine to be closer to the treatment location than those of control site animals and daily movement rates of bait station site feral swine to be 39% greater than movement rates of control site animals. Based on our observation that only 62% of feral swine trapped in proximity to the bait station used it, we cannot recommend baiting as an alternative to fences for containing animals during culling activities. However, there is value in using bait stations to describe patterns of feral swine movements, facilitate observation, and improve efficacy when conducting removals. PMID- 22305878 TI - Animal health surveillance applications: The interaction of science and management. AB - Animal health surveillance is an ever-evolving activity, since health- and risk related policy and management decisions need to be backed by the best available scientific evidence and methodology. International organizations, trade partners, politicians, media and the public expect fast, understandable, up-to-date presentation and valid interpretation of animal disease data to support and document proper animal health management - in crises as well as in routine control applications. The delivery and application of surveillance information need to be further developed and optimized, and epidemiologists, risk managers, administrators and policy makers need to work together in order to secure progress. Promising new developments in areas such as risk-based surveillance, spatial presentation and analysis, and genomic epidemiology will be mentioned. Limitations and areas in need of further progress will be underlined, such as the general lack of a wide and open exchange of international animal disease surveillance data. During my more than 30 year career as a professor of Veterinary Epidemiology I had the good fortune of working in challenging environments with different eminent colleagues in different countries on a variety of animal health surveillance issues. My career change from professor to Chief Veterinary Officer (CVO) - "from science to application" - was caused by my desire to see for myself if and how well epidemiology would actually work to solve real-life problems as I had been telling my students for years that it would. Fortunately it worked for me! The job of a CVO is not that different from that of a professor of Veterinary Epidemiology; the underlying professional principles are the same. Every day I had to work from science, and base decisions and discussions on documented evidence - although sometimes the evidence was incomplete or data were simply lacking. A basic understanding of surveillance methodology is very useful for a CVO, since it provides a sound working platform not only for dealing with immediate questions when new or emerging disease situations arise, but also for more long-term activities, such as policy development, contingency planning and trade negotiations. Animal health issues, which emerged during my eight years as a CVO in Denmark from 1999 to 2007, will be used as examples, including BSE, FMD, HPAI and Trichinella testing. Emphasis will be placed on how science-based surveillance methodology and tools were developed, applied and documented. PMID- 22305879 TI - Geographical BSE risk assessment and its impact on disease detection and dissemination. AB - Bovine Spongiform Encephalopathy (BSE) rapidly evolved into an issue of major public concern particularly when, in 1996, evidence was provided that this disease had crossed the species barrier and infected humans in the UK with what has become known as "variant Creutzfeldt Jakob Disease" (vCJD). The aim of this paper is to describe the European Geographical BSE risk assessment (GBR) that was successfully used for assessing the qualitative likelihood that BSE could be present in a country where it was not yet officially recognized. It also discusses how this can lead to risk-based and therefore preventive management of BSE at national and international levels. The basic assumption of the GBR method is that the BSE agent is initially introduced into a country's domestic cattle production system through the importation of contaminated feedstuffs or live cattle. This is referred to as an "external challenge". The ability of the system to cope with such a challenge is, in turn, referred to as its "stability": a stable system will not allow the BSE agent to propagate and amplify following its introduction, while an unstable system will. The BSE-status of a country assessed by this system was used by the European Commission as the basis for trade legislation rules for cattle and their products. The GBR was an invaluable tool in evaluating the potential global spread of BSE as it demonstrated how a disease could be transferred through international trade. This was shown to be a critical factor to address in reducing the spread and amplification of BSE throughout the world. Furthermore, GBR resulted in the implementation of additional measures and management activities both to improve surveillance and to prevent transmission within the cattle population. PMID- 22305880 TI - Ensuring that human rights and appropriate evidence endure as immunisation cornerstones. PMID- 22305881 TI - Exacerbation of myocardial dysfunction and autonomic imbalance contributes to the estrogen-dependent chronic hypotensive effect of ethanol in female rats. AB - Our previous studies showed that the hypotensive effect of chronic ethanol in female rats is reduced by ovariectomy (OVX) rats and was restored after estrogen replacement (OVXE(2)). Further, in randomly cycling rats, chronic ethanol increased cardiac parasympathetic dominance and subsequently reduced myocardial contractility and blood pressure (BP). In this study, we tested the hypothesis that alterations in myocardial contractility and sympathovagal control account for the E(2) exacerbation of the hemodynamic effects of ethanol. BP, myocardial contractility (+dP/dt(max)), and spectral cardiovascular autonomic profiles were evaluated in radiotelemetered OVX, and OVXE(2) rats receiving liquid diet with or without ethanol (5%, w/v) for 13 weeks. In OVX rats, ethanol caused modest hypotension along with significant increases in +dP/dt(max) during weeks 2-5. The high-frequency (IBI(HF), 0.75-3 Hz) and low-frequency (IBI(LF), 0.25-0.75 Hz) bands of interbeat intervals were briefly increased and decreased, respectively, by ethanol. Compared with its effects in OVX rats, chronic treatment of OVXE(2) rats with ethanol elicited significantly greater and more sustained reductions in systolic (SBP) and diastolic (DBP) blood pressures and +dP/dt(max). Altered sympathovagal balance and parasympathetic overactivity were more evident in ethanol-treated OVXE(2) rats as suggested by the sustained: (i) increases in high frequency bands of interbeat intervals (IBI(HF), 0.75-3 Hz), and (ii) decreases in low-frequency IBI bands (IBI(LF), 0.25-0.75 Hz), IBI(LF/HF) ratio and +dP/dt(max). The plasma ethanol concentration was not affected by changes in the hormonal milieu. These findings suggest that estrogen exacerbates the ethanol evoked reductions in myocardial contractility and BP and the associated parasympathetic overactivity in female rats. PMID- 22305882 TI - Leonurine attenuates lipopolysaccharide-induced inflammatory responses in human endothelial cells: involvement of reactive oxygen species and NF-kappaB pathways. AB - Leonurine, an active alkaloid of Traditional Chinese Medicine Herba leonuri, displayed cardioprotective effects by anti-oxidative and anti-apoptotic activities in vitro and in vivo. Herein, we explored the effects and possible mechanisms of leonurine on lipopolysaccharide (LPS)-induced inflammatory responses in human umbilical vein endothelial cells (HUVEC). We found that leonurine pretreatment concentration-dependently attenuated LPS-induced mRNA expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and monocyte chemoattractant protein-1. Meanwhile, LPS-mediated expression/release of ICAM-1, VCAM-1, and cyclooxygenase 2, and tumor necrosis factor-alpha was also reduced by leonurine. In addition, we confirmed that leonurine suppressed degradation of IkappaBalpha and phosphorylation of nuclear factor-kappaB (NF-kappaB) p65 as well as production of intracellular reactive oxygen species in a concentration dependent manner. Furthermore, the cytoprotective enzyme heme oxygenase-1 could be upregulated in leonurine-treated HUVEC. Our present results indicated leonurine exerted beneficial effects in inflammatory conditions partly through inhibition of reactive oxygen species and NF-kappaB signaling pathways. PMID- 22305883 TI - An investigation on characteristics of rainbow trout coated using chitosan assisted with thyme essential oil. AB - Our study aimed to determine the nutritional, textural and sensorial characteristics of butterfly-shaped rainbow trout which is coated by using enriched chitosan with thyme EO during 15 days of refrigerated storage (5+/-1 degrees C). The treatments were Cs (chitosan; 2%, w/v), Cs+T (chitosan; 2%, w/v and Thymus vulgaris EO; 1%, v/v) and C (uncoated control samples). The composition of the EO was investigated by GC/MS. Generally, the EO was found to be rich in the active monoterpene phenols (thymol and carvacrol) and their corresponding monoterpene hydrocarbon precursors such as gamma-terpinene and the oxygenated monoterpenes such as linalool. Nineteen constituent out of 116, representing 86.79% of the EO were identified, of which the major ones were thymol (3.63%), carvacrol (21.89%), gamma-terpinen (2.05%), and linalool (9.04%). Furthermore, textural and sensorial analyses were performed. Our results demonstrated chitosan coating helped with thyme EO made no unfavorable change in taste. Also it can enhance nutritional, textural and sensorial characteristics of butterfly-shaped rainbow trout during 15 days of refrigerated storage. PMID- 22305884 TI - In vitro antioxidant activities of the polysaccharides from Tricholoma lobayense. AB - The antioxidant activities of three polysaccharide components (TLH-1, TLH-2, TLH 3) extracted from Tricholoma lobayense were evaluated by three different in vitro methods, namely superoxide radical (O(2)(-)) scavenging activity, inhibition of mice erythrocyte hemolysis (MEH) and malondialdehyde (MDA) mediated by hydrogen peroxide (H(2)O(2)) and investigation of oxidative modification of human serum albumin (HSA) induced by 2,2-azobis(2-amidinopropane)dihydrochloride (AAPH) through fluorescence spectroscopy. The antioxidant experiments showed that the polysaccharides had a notable activity in scavenging O(2)(-) in a concentration dependent manner; H(2)O(2)-induced MEH and formation of MDA were effectively inhibited; by fluorescence spectroscopy, it was demonstrated that the polysaccharides could obviously inhibit AAPH-induced oxidative modification of HSA. The experimental data obtained from the in vitro models clearly revealed that TLH-3 had stronger antioxidant potency than TLH-1 and TLH-2, which indicated that TLH-3 might be exploited as effective natural antioxidant to alleviate oxidative stress. PMID- 22305885 TI - Differential maturation of the molecular clockwork in the olfactory bulb and suprachiasmatic nucleus of the rabbit. AB - Recent studies suggest that the main olfactory bulb (OB) represents a functional circadian pacemaker. In many altricial mammals, during pre-visual stages of development the olfactory system plays a vital role in their survival. One remarkable example is the European rabbit; the newborns are normally raised in a dark nursery burrow, and the lactating female briefly visits her young approximately once every 24 h. Under these conditions, newborn rabbits depend on the circadian system to anticipate the arrival of the lactating doe as well as on pheromonal cues on the mother's ventrum to locate nipples and suckle efficiently. To investigate the development of the rabbit's circadian system, we characterized the 24-h pattern of expression of clock genes in the OB and suprachiasmatic nucleus (SCN) of pre-visual week-old rabbits and compared this with the pattern of expression in visual juvenile rabbits several weeks after weaning. We report for the first time that Per1, Cry1, and Bmal1 are expressed in the OB of newborn and juvenile rabbits. In addition, the diurnal pattern of clock gene expression develops earlier in the OB than in the SCN of newborn rabbits. Given the early maturation of the molecular clockwork and the biological relevance of this structure during development, it is possible that the OB plays an important role in temporal regulation during pre-visual life in rabbits. PMID- 22305887 TI - Microbial community analysis of Korean soybean pastes by next-generation sequencing. AB - Soybean pastes, doenjang, have long been consumed as a fortified protein source in Korea. The quality of doenjang is determined by fermentation and Bacillus subtilis is suspected to be the main microorganism responsible. In the current culture-independent analysis, 17,675 bacterial sequences were derived from nine local and two commercial brands of doenjang samples by a barcoded pyrosequencing method targeting the hyper-variable regions V1/V2 of the 16S rRNA gene. In contrast to what has previously been found using plating or conventional molecular biology based methods, doenjang contains a diversity of bacterial species (total 208 species) and each doenjang reflects a region-specific bacterial community. While the Bacillus species was thought to be dominant in soybean pastes, we found that they were in high abundance (58.3-91.6%) only in samples from the central region of Korea, whereas lactic acid bacteria (LAB) (39.8-77.7%) were the dominant bacterial members of other doenjang samples. Compared to local brands of doenjang, commercial brands contain simple microbial communities dominated by Tetragenococcus and Staphylococcus that resemble the microbial communities of Japanese miso; this suggests that artificial inoculation was used for the quality control and standardization of doenjang. In this study, a massive sequencing approach was applied for the first time to analyze the microbial communities of different doenjang samples. Thus, we have determined that massive sequencing is a valid approach for assessing the overall microbial community of Korean fermented soybean pastes. PMID- 22305886 TI - Disruptions in serotonergic regulation of cortical glutamate release in primate insular cortex in response to chronic ethanol and nursery rearing. AB - Early-life stress has been shown to increase susceptibility to anxiety and substance abuse. Disrupted activity within the anterior insular cortex (AIC) has been shown to play a role in both of these disorders. Altered serotonergic processing is implicated in controlling the activity levels of the associated cognitive networks. We therefore investigated changes in both serotonin receptor expression and glutamatergic synaptic activity in the AIC of alcohol-drinking rhesus monkeys. We studied tissues from male rhesus monkeys raised under two conditions: Male rhesus monkeys (1) "mother reared" (MR) by adult females (n=9) or (2) "Nursery reared" (NR), that is, separated from their mothers and reared as a separate group under surrogate/peer-reared conditions (n=9). The NR condition represents a long-standing and well-validated nonhuman primate model of early life stress. All monkeys were trained to self-administer ethanol (4% w/v) or an isocaloric maltose-dextrin control solution. Subsets from each rearing condition were then given daily access to ethanol, water, or maltose-dextrin for 12 months. Tissues were collected at necropsy and were further analyzed. Using real time RT PCR we found that ethanol-naive, NR monkeys had lower AIC levels of 5-HT(1A) and 5-HT(2A) receptor mRNA compared with ethanol-naive, MR animals. Although NR monkeys consumed more ethanol over the 12-month period compared with MR animals, both MR and NR animals expressed greater 5-HT(1A) and 5-HT(2A) receptor mRNA levels following chronic alcohol self-administration. The interaction between nursery-rearing conditions and alcohol consumption resulted in a significant enhancement of both 5-HT(1A) and 5-HT(2A) receptor mRNA levels such that lower expression levels observed in nursery-rearing conditions were not found in the alcohol self-administration group. Using voltage clamp recordings in the whole cell configuration we recorded excitatory postsynaptic currents in both ethanol naive and chronic self-administration groups of NR and MR monkeys. Both groups that self-administered ethanol showed greater glutamatergic activity within the AIC. This AIC hyperactivity in MR alcohol-consuming monkeys was accompanied by an increased sensitivity to regulation by presynaptic 5-HT(1A) receptors that was not apparent in the ethanol-naive, MR group. Our data indicate that chronic alcohol consumption leads to greater AIC activity and may indicate a compensatory upregulation of presynaptic 5-HT(1A) receptors. Our results also indicate that AIC activity may be less effectively regulated by 5-HT in ethanol-naive NR animals than in NR monkeys in response to chronic ethanol self-administration. These data suggest possible mechanisms for increased alcohol seeking and possible addiction potential among young adults who had previously experienced early-life stress that include disruptions in both AIC activity and serotonin system dynamics. PMID- 22305888 TI - Quantitative proteomic analysis of bacterial enzymes released in cheese during ripening. AB - Due to increasingly available bacterial genomes in databases, proteomic tools have recently been used to screen proteins expressed by micro-organisms in food in order to better understand their metabolism in situ. While the main objective is the systematic identification of proteins, the next step will be to bridge the gap between identification and quantification of these proteins. For that purpose, a new mass spectrometry-based approach was applied, using isobaric tagging reagent for quantitative proteomic analysis (iTRAQ), which are amine specific and yield labelled peptides identical in mass. Experimental Swiss-type cheeses were manufactured from microfiltered milk using Streptococcus thermophilus ITG ST20 and Lactobacillus helveticus ITG LH1 as lactic acid starters. At three ripening times (7, 20 and 69 days), cheese aqueous phases were extracted and enriched in bacterial proteins by fractionation. Each sample, standardised in protein amount prior to proteomic analyses, was: i) analysed by 2D-electrophoresis for qualitative analysis and ii) submitted to trypsinolysis, and labelled with specific iTRAQ tag, one per ripening time. The three labelled samples were mixed together and analysed by nano-LC coupled on-line with ESI-QTOF mass spectrometer. Thirty proteins, both from bacterial or bovine origin, were identified and efficiently quantified. The free bacterial proteins detected were enzymes from the central carbon metabolism as well as stress proteins. Depending on the protein considered, the quantity of these proteins in the cheese aqueous extract increased from 2.5 to 20 fold in concentration from day 7 to day 69 of ripening. PMID- 22305889 TI - Reduction of Listeria monocytogenes in queso fresco cheese by a combination of listericidal and listeriostatic GRAS antimicrobials. AB - Single and combined effects of three GRAS (generally recognized as safe) antimicrobials including, bacteriophage P100 (phage P100), lauric arginate (LAE), and potassium lactate-sodium diacetate mixture (PL-SD) were evaluated against Listeria monocytogenes cold growth in queso fresco cheese (QFC). The fate of phage P100 when exposed to LAE (200 ppm) or PL-SD (2.8% PL and 0.2% SD) was determined at 4 degrees C and 30 degrees C in a broth model. Phage P100 was found to be stable in the presence of these antimicrobial agents as plaque forming units (PFU) did not vary between control, LAE or PL-SD treatments. When 9 log CFU/ml of stationary phase cells of L. monocytogenes was exposed to these antimicrobials in tryptic soy broth, there was a 3 to 5 log CFU/ml reduction with phage P100 and a complete 9 log CFU/ml reduction with LAE but no measurable reduction with PL-SD after 24h at 4 degrees C or 30 degrees C. In QFC, the L. monocytogenes populations increased from the initial 3.5 log CFU/cm(2) to 7.7 log CFU/cm(2) in 28 days at 4 degrees C. Treatment with 7.8 log PFU/cm(2) of phage P100 or 200 ppm of LAE showed strong listericidal effect initially by reducing L. monocytogenes counts by 2 to 3.5-4 log CFU/cm(2) while there was a subsequent regrowth of L. monocytogenes at 4 degrees C. Treatment with PL-SD showed strong listeriostatic effect without decreasing L. monocytogenes counts but growth was prevented for 28 days at 4 degrees C. Only the combined treatment of listericidal phage P100 or LAE with listeriostatic PL-SD reduced the initial L. monocytogenes counts by 2-4 log CFU/cm(2) and also kept the L. monocytogenes counts at that reduced level in QFC for 28 days at 4 degrees C. PMID- 22305890 TI - Atorvastatin sensitizes human non-small cell lung carcinomas to carboplatin via suppression of AKT activation and upregulation of TIMP-1. AB - Platinum-based chemotherapy is the standard treatment for advanced non-small-cell lung carcinomas (NSCLCs). However, the antitumoral effect of carboplatin displays unsatisfactory in NSCLCs treatment due to the AKT pathway-mediated carboplatin insensitive in NSCLCs treatment. Previous studies have shown that statins have antitumor activity, but it is unknown whether atorvastatin can reverse carboplatin resistance in lung cancer. Treatment with atorvastatin and carboplatin reduced the growth of xenograft A549 tumors in nude mice and enhanced the survival rate compared with carboplatin alone. Atorvastatin in combination with carboplatin had stronger effects on growth inhibition and apoptosis of NSCLC than either agent used individually. Carboplatin conferred anti-invasive effect in NSCLC cells mainly through inhibition of AKT activity and resultant upregulation of TIMP-1. However, the inhibitory effect on AKT activity by carboplatin was short-term. Additional atorvastatin administration resulted in synergistic inhibition of NSCLC cell invasion and stimulation of TIMP-1 expression with carboplatin through stronger and persistent inhibition of AKT activity both in vivo and in vitro. The synergy of atorvastatin and carboplatin was confirmed using another human lung carcinoma cell line (H1299). Altogether, our data demonstrate that atorvastatin may overcome carboplatin resistance in lung cancer by suppressing AKT activity and upregulating TIMP-1. A combination of atorvastatin and carboplatin may be an effective strategy in clinical therapy against NSCLCs. PMID- 22305891 TI - Tyrosines 303/343/353 within the Sprouty-related domain of Spred2 are essential for its interaction with p85 and inhibitory effect on Ras/ERK activation. AB - Sprouty-related EVH1 domain (Spred) proteins modulate growth factor receptor signaling by inhibiting the Ras/ERK pathway. In particular, the Sprouty-related domain (SPR) of Spred2 is essential for the Spred2-mediated inhibitory effect, but the molecular mechanism is largely unknown. We show here that the p85 subunit of phosphatidylinositol 3-kinase (PI3K) is a new binding partner of Spred2 via interaction with the SPR domain. Mutation of three tyrosines 303/343/353 within the SPR domain not only abolish EGF-induced p85 binding to Spred2 but also attenuate the inhibitory effect on Ras/ERK activation by Spred2. This results in increased Hela cell proliferation and neurite outgrowth in PC12 cells. We further demonstrate that p85 binding to Spred2 enhances the Spred2-mediated inhibitory effect via increased Ras binding to Spred2 and decreased Spred2 ubiquitination. We also show that Spred2 constitutively associates with epidermal growth factor receptor (EGFR) via its SPR domain and dissociates from EGFR upon EGF stimulation. Moreover, mutation of tyrosines 303/343/353 together enhances Spred2 binding to EGFR. Taken together, these results suggest critical roles of the three tyrosines 303/343/353 within the SPR domain in regulating Spred2 signaling and provide a mechanism for the SPR domain of Spred2 to mediate the inhibitory effect on the Ras/ERK pathway. PMID- 22305892 TI - A simple protocol for Matrix Assisted Laser Desorption Ionization- time of flight mass spectrometry (MALDI-TOF-MS) analysis of lipids and proteins in single microsamples of paintings. AB - A simple protocol, based on Bligh-Dyer (BD) extraction followed by MALDI-TOF-MS analysis, for fast identification of paint binders in single microsamples is proposed. For the first time it is demonstrated that the BD method is effective for the simultaneous extraction of lipids and proteins from complex, and atypical matrices, such as pigmented paint layers. The protocol makes use of an alternative denaturing anionic detergent (RapiGestTM) in order to improve efficiency of protein digestion and purification step. Detection of various lipid classes, such as triacylglycerols (TAGs) and phospholipids (PLs), and their oxidation by-products was accomplished, whereas proteins could be identified by peptide mass fingerprinting. The effect of pigments on ageing of lipids and proteins was also investigated. Finally, the proposed protocol was successfully applied to the study of a late-15th century Italian panel painting allowing the identification of various proteinaceous and lipid sections in organic binders, such as egg yolk, egg white, animal glue, casein, and drying oil. PMID- 22305893 TI - On-line sample pre-concentration in microfluidic devices: a review. AB - On-line sample preconcentration is an essential tool in the development of microfluidic-based separation platforms. In order to become more competitive with traditional separation techniques, the community must continue to develop newer and more novel methods to improve detection limits, remove unwanted sample matrix components that disrupt separation performance, and enrich/purify analytes for other chip-based actions. Our goal in this review is to familiarize the reader with many of the options available for on-chip concentration enhancement with a focus on those manuscripts that, in our assessment, best describe the fundamental principles that govern those enhancements. Sections discussing both electrophoretic and nonelectrophoretic modes of preconcentration are included with a focus on device design and mechanisms of preconcentration. This review is not meant to be a comprehensive collection of every available example, but our hope is that by learning how on-line sample concentration techniques are being applied today, the reader will be inspired to apply these techniques to further enhance their own programs. PMID- 22305894 TI - Development and validation of a methodology for uranium radiochronometry reference material preparation. AB - The paper describes a methodology for a reference material preparation to be used for the determination of the production date (i.e. the time elapsed since the last chemical processing) of uranium materials based on the (230)Th/(234)U radiochronometer. The reference material was prepared from highly enriched uranium by a complete separation of thorium decay products, thus zeroing the initial daughter nuclide concentration at known time. The complete elimination of thorium from the starting material was verified by gamma spectrometric measurements and by addition of a (232)Th tracer to the material and its re measurement in the final product after the separation. The validation of the methodology was carried out subsequently by comparing the ingrown daughter nuclide (230)Th and the measured (230)Th/(234)U ratio after recorded times following the last chemical separation with the calculated values obtained on the basis of their respective half-lives. The prepared reference material can be used as a quality control material for age determination of uranium in nuclear forensics and safeguards as well as for method validation. PMID- 22305895 TI - Identification of human protein complexes from local sub-graphs of protein protein interaction network based on random forest with topological structure features. AB - In the post-genomic era, one of the most important and challenging tasks is to identify protein complexes and further elucidate its molecular mechanisms in specific biological processes. Previous computational approaches usually identify protein complexes from protein interaction network based on dense sub-graphs and incomplete priori information. Additionally, the computational approaches have little concern about the biological properties of proteins and there is no a common evaluation metric to evaluate the performance. So, it is necessary to construct novel method for identifying protein complexes and elucidating the function of protein complexes. In this study, a novel approach is proposed to identify protein complexes using random forest and topological structure. Each protein complex is represented by a graph of interactions, where descriptor of the protein primary structure is used to characterize biological properties of protein and vertex is weighted by the descriptor. The topological structure features are developed and used to characterize protein complexes. Random forest algorithm is utilized to build prediction model and identify protein complexes from local sub-graphs instead of dense sub-graphs. As a demonstration, the proposed approach is applied to protein interaction data in human, and the satisfied results are obtained with accuracy of 80.24%, sensitivity of 81.94%, specificity of 80.07%, and Matthew's correlation coefficient of 0.4087 in 10-fold cross-validation test. Some new protein complexes are identified, and analysis based on Gene Ontology shows that the complexes are likely to be true complexes and play important roles in the pathogenesis of some diseases. PCI-RFTS, a corresponding executable program for protein complexes identification, can be acquired freely on request from the authors. PMID- 22305896 TI - Determination of oxytetracycline in milk samples by polymer inclusion membrane separation coupled to high performance liquid chromatography. AB - The determination of oxytetracycline in milk samples using a polymer inclusion membrane concept with high performance liquid chromatography (HPLC) was studied. The membranes developed are composed by cellulose acetate as polymer base, Cyanex 923 as carrier and o-nitrophenyl octyl ether as plasticizer. In the optimal conditions, the method exhibits good linearity in the range 0.03-0.20 mg L(-1) with a limit of detection and quantification of 8.2 and 27.3 MUg L(-1) respectively. The method was successfully applied to the analysis of milk samples with high selectivity. PMID- 22305897 TI - Metabolic fingerprinting of high-fat plasma samples processed by centrifugation- and filtration-based protein precipitation delineates significant differences in metabolite information coverage. AB - Metabolomics and metabolic fingerprinting are being extensively employed for improved understanding of biological changes induced by endogenous or exogenous factors. Blood serum or plasma samples are often employed for metabolomics studies. Plasma protein precipitation (PPP) is currently performed in most laboratories before LC-MS analysis. However, the impact of fat content in plasma samples on metabolite coverage has not previously been investigated. Here, we have studied whether PPP procedures influence coverage of plasma metabolites from high-fat plasma samples. An optimized UPLC-QTOF/MS metabolic fingerprinting approach and multivariate modeling (PCA and OPLS-DA) were utilized for finding characteristic metabolite changes induced by two PPP procedures; centrifugation and filtration. We used 12-h fasting samples and postprandial samples collected at 2h after a standardized high-fat protein-rich meal in obese non-diabetic subjects recruited in a dietary intervention. The two PPP procedures as well as external and internal standards (ISs) were used to track errors in response normalization and quantification. Remarkably and sometimes uniquely, the fPPP, but not the cPPP approach, recovered not only high molecular weight (HMW) lipophilic metabolites, but also small molecular weight (SMW) relatively polar metabolites. Characteristic SMW markers of postprandial samples were aromatic and branched-chain amino acids that were elevated (p<0.001) as a consequence of the protein challenge. In contrast, some HMW lipophilic species, e.g. acylcarnitines, were moderately lower (p<0.001) in postprandial samples. LysoPCs were largely unaffected. In conclusion, the fPPP procedure is recommended for processing high fat plasma samples in metabolomics studies. While method improvements presented here were clear, use of several ISs revealed substantial challenges to untargeted metabolomics due to large and variable matrix effects. PMID- 22305898 TI - Highly efficient capillary polymerase chain reaction using an oscillation droplet microreactor. AB - The current work presents the development of a capillary-based oscillation droplet approach to maximize the potential of a continuous-flow polymerase chain reaction (PCR). Through the full utilization of interfacial chemistry, a water-in oil (w/o) droplet was generated by allowing an oil-water plug to flow along a polytetrafluoroethylene (PTFE) capillary. The w/o droplet functioned as the reactor for oscillating-flow PCR to provide a stable reaction environment, accelerate reagent mixing, and eliminate surface adsorption. The capillary PCR approach proposed in the current research offers high amplification efficiency, fast reaction speed, and easy system control attributable to the oscillation droplet reactor. Experimental results show that the droplet-based micro-PCR assay requires lower reaction volume (2 MUL) and shorter reaction time (12 min) compared with conventional PCR methods. Taking the amplification of the New Delhi metallo-beta-lactamase (NDM-1) gene as an example, the present work demonstrates that the oscillation droplet PCR assay is capable of achieving high efficiency up to 89.5% and a detection limit of 10 DNA copies. The miniature PCR protocol developed in the current work is fast, robust, and low-cost, thus exhibiting the potential for expansion into various practical applications. PMID- 22305899 TI - Parallel detection, quantification, and depth profiling of peptides with dynamic secondary ion mass spectrometry (D-SIMS) ionized by C60(+)-Ar(+) co-sputtering. AB - Time-of-flight secondary ion mass spectrometry (ToF-SIMS) using pulsed C(60)(+) primary ions is a promising technique for analyzing biological specimens with high surface sensitivities. With molecular secondary ions of high masses, multiple molecules can be identified simultaneously without prior separation or isotope labeling. Previous reports using the C(60)(+) primary ion have been based on static-SIMS, which makes depth profiling complicated. Therefore, a dynamic SIMS technique is reported here. Mixed peptides in the cryoprotectant trehalose were used as a model for evaluating the parameters that lead to the parallel detection and quantification of biomaterials. Trehalose was mixed separately with different concentrations of peptides. The peptide secondary ion intensities (normalized with respect to those of trehalose) were directly proportional to their concentration in the matrix (0.01-2.5 mol%). Quantification curves for each peptide were generated by plotting the percentage of peptides in trehalose versus the normalized SIMS intensities. Using these curves, the parallel detection, identification, and quantification of multiple peptides was achieved. Low energy Ar(+) was used to co-sputter and ionize the peptide-doped trehalose sample to suppress the carbon deposition associated with C(60)(+) bombardment, which suppressed the ion intensities during the depth profiling. This co-sputtering technique yielded steadier molecular ion intensities than when using a single C(60)(+) beam. In other words, co-sputtering is suitable for the depth profiling of thick specimens. In addition, the smoother surface generated by co-sputtering yielded greater depth resolution than C(60)(+) sputtering. Furthermore, because C(60)(+) is responsible for generating the molecular ions, the dosage of the auxiliary Ar(+) does not significantly affect the quantification curves. PMID- 22305900 TI - A support for the identification of non-tryptic peptides based on low resolution tandem and sequential mass spectrometry data: the INSPIRE software. AB - A simple software, to be used as an aid in the identification of non-tryptic peptides based on low resolution (3D-ion trap) tandem (MS/MS) and sequential (MS(3)) mass spectrometry data, is presented. The program, named INSPIRE (Identification of Non-tryptic peptide Sequences based on Product Ions m/z ratios and RElative abundances), provides alternative rankings for the several candidate sequences usually arising from protein database searches when non-tryptic peptides are involved and only low resolution MS/MS data are available. The rankings, based on parameters related to m/z ratios and relative abundances of experimental product ions matching with predicted ones, can be exploited to reduce the number of candidates to be included in subsequent data processing based on MS(3) measurements. The latter usually represents a mandatory step towards a reliable peptide identification when high resolution MS/MS data are not accessible. Sets of peptide sequences arising from MS/MS-based database searches for 63 previously identified non-tryptic peptides (all generated from milk proteins) were exploited to check the INSPIRE performance. It was found that, if retrieved among candidates after the database search, the correct sequence was always ranked among the first 10 ones when parameters calculated by INSPIRE were adopted for discrimination purposes. Under the same conditions the ranks provided by popular database search programs were significantly worse in a remarkable number of cases. PMID- 22305901 TI - Multidimensional Raman spectroscopic signature of sweat and its potential application to forensic body fluid identification. AB - This proof-of-concept study demonstrated the potential of Raman microspectroscopy for nondestructive identification of traces of sweat for forensic purposes. Advanced statistical analysis of Raman spectra revealed that dry sweat was intrinsically heterogeneous, and its biochemical composition varies significantly with the donor. As a result, no single Raman spectrum could adequately represent sweat traces. Instead, a multidimensional spectroscopic signature of sweat was built that allowed for the presentation of any single experimental spectrum as a linear combination of two fluorescent backgrounds and three Raman spectral components dominated by the contribution from lactate, lactic acid, urea and single amino acids. PMID- 22305902 TI - Flow injection chemiluminescence sensor based on core-shell magnetic molecularly imprinted nanoparticles for determination of sulfadiazine. AB - A novel flow injection chemiluminescence (FI-CL) sensor for determination of sulfadiazine (SDZ) using core-shell magnetic molecularly imprinted polymers (MMIPs) as recognition element is developed. Briefly, a hydrophilic MMIPs layer was produced at the surface of Fe(3)O(4)@SiO(2) magnetic nanoparticles (MNPs) via combination of molecular imprinting and reversible stimuli responsive hydrogel. And it provided the MMIPs with excellent adsorption capacity and rapid adsorption rate due to the imprinted sites mostly situated on the surface of MMIPs. Then the prepared SDZ-MMIPs were packed into flow cell to establish a novel FI-CL sensor. The sensor provided a wide linear range for SDZ of 4.0*10(-7) to 1.0*10(-4) mol L(-1) with a detection limit of 1.54*10(-7) mol L(-1). And the relative standard deviation (RSD) for the determination of 1.0*10(-6) mol L(-1) SDZ was 2.56% (n=11). The proposed method was applied to determine SDZ in urine samples and satisfactory results were obtained. PMID- 22305903 TI - Normalization using a tagged-internal standard assay for analysis of antibody arrays and the evaluation of serological biomarkers for liver disease. AB - For minimizing systemic experimental variation in the analysis of antibody array data, we developed a novel median-centered/IgM-tagged-internal standard (TIS) assay normalization using median-centering and TIS assay-based determination of serum IgM concentrations. We evaluated five normalization methods by analyzing correlation coefficients and coefficients of variation for six serum proteins using human serum samples from normal controls (n=25) and patients with liver cirrhosis (n=25) or hepatocellular carcinoma (HCC; n=29). Median-centered normalization improved correlation coefficients, while IgM-based normalizations improved coefficients of variation. The TIS assay was more efficient, economical, and reproducible for determining IgM concentrations than enzyme-linked immunosorbent assay. Additionally, we normalized antibody array data for six serum proteins using the median-centered/IgM-TIS assay, and evaluated serum biomarkers through distribution analysis of normalized fluorescence intensities and receiver operating characteristic analyses for the diagnosis of liver cirrhosis and HCC. Apolipoprotein A-1 and a combination of alpha-fetoprotein and C-reactive protein were determined to be potential serological biomarkers for liver cirrhosis and HCC, respectively. Thus, median-centered/IgM-TIS assay normalization is a useful approach for analyzing antibody array data and evaluating serological biomarkers for the diagnosis of liver disease or cancers. PMID- 22305904 TI - Multiplex dipstick immunoassay for semi-quantitative determination of Fusarium mycotoxins in cereals. AB - A multiplex dipstick immunoassay based method for the simultaneous determination of major Fusarium toxins, namely zearalenone, T-2 and HT-2 toxins, deoxynivalenol and fumonisins in wheat, oats and maize has been developed. The dipstick format was based on an indirect competitive approach. Four test lines (mycotoxin-BSA conjugates) and one control line were located on the strip membrane. Labelled antibodies were freeze-dried within the microwell. Two matrix-related sample preparation protocols have been developed for wheat/oats (not containing fumonisins) and maize (containing fumonisins) respectively. The use of a methanol/water mixture for sample preparation allowed recoveries in the range 73 109% for all mycotoxins in all tested cereals, with relative standard deviation less than 10%. The optimized immunoassay was able to detect target mycotoxins at cut off levels equal to 80% of EU maximum permitted levels, i.e. 280, 400, 1400 and 3200 MUg kg(-1), respectively, for zearalenone, T-2/HT-2 toxins, deoxynivalenol and fumonisins in maize, and 80, 400 and 1400 MUg kg(-1), respectively, for zearalenone, T-2/HT-2 toxins and deoxynivalenol in wheat and oats. Analysis of naturally contaminated samples resulted in a good agreement between multiplex dipstick and validated confirmatory LC-MS/MS. The percentage of false positive results was less than or equal to 13%, whereas no false negative results were obtained. Data on the presence/absence of 6 mycotoxins at levels close to EU regulatory levels were obtained within 30 min. The proposed immunoassay protocol is rapid, inexpensive, easy-to-use and fit for purpose of rapid screening of mycotoxins in cereals. PMID- 22305905 TI - Surface imprinted thin polymer film systems with selective recognition for bovine serum albumin. AB - Molecularly imprinted polymers are synthetic antibody mimics formed by the crosslinking of organic or inorganic polymers in the presence of an analyte which yields recognitive polymer networks with specific binding pockets for that biomolecule. Surface imprinted polymers were synthesized via a novel technique for the specific recognition of bovine serum albumin (BSA). Thin films of recognitive networks based on 2-(dimethylamino)ethyl methacrylate (DMAEMA) as the functional monomer and varying amounts of either N,N'-methylenebisacrylamide (MBA) or poly(ethylene glycol) (400) dimethacrylate (PEG400DMA) as the crosslinking agent were synthesized via UV free-radical polymerization and characterized. A clear and reproducible increase in recognition of the template BSA was demonstrated for these systems at 1.6-2.5 times more BSA recognized by the MIP sample relative to the control polymers. Additionally, these polymers exhibited selective recognition of the template relative to competing proteins with up to 2.9 times more BSA adsorbed than either glucose oxidase or bovine hemoglobin. These synthetic antibody mimics hold significant promise as the next generation of robust recognition elements in a wide range of bioassay and biosensor applications. PMID- 22305906 TI - Determination of sodium, potassium, calcium and magnesium cations in biodiesel by ion chromatography. AB - This work reports an ion chromatographic (IC) method for the quantitative determination of inorganic cations (Na(+), K(+), Mg(2+) and Ca(2+)) in biodiesel samples that were synthesized from different vegetable oils and fat. The proposed method uses water extraction, heating and ultrasound. The limits of detection (LOD) for each ion, in milligrams of the analyte per kilogram of biodiesel (mgkg( 1)), were respectively: 0.11 (Na(+)); 0.42 (K(+)); 0.23 (Ca(2+)); and 0.36 (Mg(2+)). The accuracy of the method was studied through recovery tests. For comparison, two samples were also analyzed using an Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) procedure. The paired Student t test and the Snedecor F test showed that both methods offer equivalent results in terms of accuracy and precision. The operational simplicity, accuracy and precision of the proposed method suggest that it can be a good alternative for the determination of inorganic cations in biodiesel samples. PMID- 22305907 TI - Cationic cyclodextrins chemically-bonded chiral stationary phases for high performance liquid chromatography. AB - Two covalently bonded cationic beta-CD chiral stationary phases (CSPs) prepared by graft polymerization of 6(A)-(3-vinylimidazolium)-6-deoxyperphenylcarbamate beta-cyclodextrin chloride or 6(A)-(N,N-allylmethylammonium)-6 deoxyperphenylcarbamoyl-beta-cyclodextrin chloride onto silica gel were successfully applied in high-performance liquid chromatography (HPLC). Their enantioseparation capability was examined with 12 racemic pharmaceuticals and 6 carboxylic acids. The results indicated that imidazolium-containing beta-CD CSP afforded more favorable enantioseparations than that containing ammonium moiety under normal-phase HPLC. The cationic moiety on beta-CD CSPs could form strong hydrogen bonding with analytes in normal-phase liquid chromatography (NPLC) to enhance the analytes' retention and enantioseparations. In reversed-phase liquid chromatography (RPLC), the analytes exhibited their maximum retention when the pH of mobile phase was close to their pK(a) value. Inclusion complexation with CD cavity and columbic/ionic interactions with cationic substituent on the CD rim would afford accentuated retention and enantioseparations of the analytes. PMID- 22305908 TI - Immobilization of chitosan in sol-gel phases for chiral open-tubular capillary electrochromatography. AB - Three different approaches for immobilizing cross-linked chitosan molecules (CS s) in sol-gel phases to form chiral OT-CEC capillaries were comparatively investigated in this study. To synthesize column I, a bare capillary was first silanized with triethoxysilane (TEOS) and then reacted with the reaction product of 3-glycidyloxypropyltrimethoxysilane (GTS) and CS-s. Column II was prepared by the silanization of a bare capillary with a mixture of TEOS and GTS silanes followed by reaction with CS-s. To obtain column III, all the reagents, including TEOS, GTS, and CS-s were reacted together in a bare capillary. The SEM images showed that the column I phase consisted of two distinct layers, GTS and TEOS sol gel films, while column II and III phases were homogeneous phases. By elemental analysis, the chitosan contents of the columns were found to decrease in the order column I>II>III, which corresponded to the order of the electroosmotic mobility values obtained from the measurements of the electroosmotic flow in the columns. The retention factor and the selectivity for the chiral separation of phenylglycine enantiomers in the optimized Tris running buffer (100 mM, pH 7.5) also followed this decreasing order. Besides the strength of the interaction with the immobilized functional chitosan, the hydrophobicity of the column affected the resolution of enantiomeric samples. The hydrophilic alanine sample could only be resolved by column III, but the hydrophobic tryptophan and catechin enantiomers were better separated by columns I and II. A reverse-phase mechanism has been found in the separations. Furthermore, the resolution and analysis time of column I and II phases were superior to the phase simply bonded with molecular chitosan. PMID- 22305909 TI - Computer-aided molecular modeling study of enantioseparation of iodiconazole and structurally related triadimenol analogues by capillary electrophoresis: chiral recognition mechanism and mathematical model for predicting chiral separation. AB - Chiral separation of iodiconazole, a new antifungal drug, and 12 new structurally related triadimenol analogues had been developed by capillary electrophoresis (CE) using hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD) as the chiral selector. The effect of structural features of analytes on Deltat and R(s) was studied under the optimum separation conditions. Using molecular docking technique and binding energy calculations, the inclusion process between HP-gamma-CD and enantiomers was investigated and chiral recognition mechanisms were discussed. The results suggest that hydrogen bonding between fluorine at position 4 of the phenyl group beside the chiral carbon and the hydroxyl group on the HP-gamma-CD rim and face to face pi-pi interactions between two phenyl rings highly contributed to the enantiorecognition process between HP-gamma-CD and iodiconazole. The N-methyl group beside chiral carbon also played an important role in enantiomeric separation. Additionally, the big difference in binding energy (DeltaDeltaE) highly contributed to good separation in the presence of HP gamma-CD chiral selector, which may be a helpful initial guide for chiral selector selection and predicting the result of enantioseparation. Furthermore, the new mathematical equation established based on the results of molecular mechanics calculations exhibited good capability in predicting chiral separation of these triadimenol analogues using HP-gamma-CD mediated CE. PMID- 22305910 TI - Ventricular flutter triggered by fever in a patient with Brugada syndrome. AB - Brugada syndrome is a clinical-electrocardiographic entity predisposing to malignant ventricular arrhythmias. The typical arrhythmia is polymorphic ventricular tachycardia, which can potentially degenerate to ventricular fibrillation. Monomorphic ventricular tachycardia is uncommon. Our group is reporting the case of a 39-year-old man with known Brugada syndrome who developed ventricular flutter while febrile. Fever has previously been shown to unmask Brugada changes and to induce ventricular arrhythmias. The appearance of monomorphic ventricular tachycardia potentially attributable to sodium-channel dysfunction further confounds the mechanism of arrhythmogenesis in Brugada syndrome. This curious occurrence further underlines the likely complex nature of arrhythmogenesis in Brugada syndrome. PMID- 22305911 TI - Cellulose affinity purification of fusion proteins tagged with fungal family 1 cellulose-binding domain. AB - N- or C-terminal fusions of red-fluorescent protein (RFP) with various fungal cellulose-binding domains (CBDs) belonging to carbohydrate binding module (CBM) family 1 were expressed in a Pichia pastoris expression system, and the resulting fusion proteins were used to examine the feasibility of large-scale affinity purification of CBD-tagged proteins on cellulose columns. We found that RFP fused with CBD from Trichoderma reesei CBHI (CBD(Tr)(CBHI)) was expressed at up to 1.2g/l in the culture filtrate, which could be directly injected into the cellulose column. The fusion protein was tightly adsorbed on the cellulose column in the presence of a sufficient amount of ammonium sulfate and was efficiently eluted with pure water. Bovine serum albumin (BSA) was not captured under these conditions, whereas both BSA and the fusion protein were adsorbed on a phenyl column, indicating that the cellulose column can be used for the purification of not only hydrophilic proteins but also for hydrophobic proteins. Recovery of various fusion proteins exceeded 80%. Our results indicate that protein purification by expression of a target protein as a fusion with a fungal family 1 CBD tag in a yeast expression system, followed by affinity purification on a cellulose column, is simple, effective and easily scalable. PMID- 22305912 TI - Escalation of methamphetamine self-administration in adolescent and adult rats. AB - BACKGROUND: Methamphetamine (METH) use has increased substantially in the last 10 years and poses a serious health concern, especially for young populations. Drug abuse primarily begins during adolescence, when uninhibited and excessive and drug intake is a common occurrence; thus, understanding the developmental patterns of addiction during this critical period is an essential step in its prevention. In the present study, the effect of age on the vulnerability to METH abuse was examined using a rat model of bingeing (i.e., escalation). METHODS: Adolescent and adult rats were compared during short (ShA, 2-h) and long-access (LgA, 6-h) to METH self-administration. On postnatal (PN) days 23 (adolescents) and 90 (adults), rats were implanted with i.v. catheters and trained to lever press for infusions of METH (0.05mg/kg) during 2-h sessions. Once the rats reached a steady rate of METH self-administration, they were divided into ShA or LgA groups and allowed to self-administer METH for 15 additional days. RESULTS: Results indicated that adolescent rats earned significantly more infusions than adults under the LgA condition, but the age groups did not differ during ShA. Adolescents, but not adults, also significantly increased (i.e., escalated) METH self-administration across the 15 days of testing under the LgA condition. Further analysis indicated excessive responding during infusions in the LgA METH exposed adolescents compared to the other groups, suggesting elevated impulsivity or motivation for drug. CONCLUSION: These results demonstrate that adolescents are more vulnerable to the escalation of METH than adults during LgA. PMID- 22305913 TI - Photo-induced electron transfer in intact cells of Rubrivivax gelatinosus mutants deleted in the RC-bound tetraheme cytochrome: insight into evolution of photosynthetic electron transport. AB - Deletion of two of the major electron carriers, the reaction center-bound tetrahemic cytochrome and the HiPIP, involved in the light-induced cyclic electron transfer pathway of the purple photosynthetic bacterium, Rubrivivax gelatinosus, significantly impairs its anaerobic photosynthetic growth. Analysis on the light-induced absorption changes of the intact cells of the mutants shows, however, a relatively efficient photo-induced cyclic electron transfer. For the single mutant lacking the reaction center-bound cytochrome, we present evidence that the electron carrier connecting the reaction center and the cytochrome bc(1) complex is the High Potential Iron-sulfur Protein. In the double mutant lacking both the reaction center-bound cytochrome and the High Potential Iron-sulfur Protein, this connection is achieved by the high potential cytochrome c(8). Under anaerobic conditions, the halftime of re-reduction of the photo-oxidized primary donor by these electron donors is 3 to 4 times faster than the back reaction between P(+) and the reduced primary quinone acceptor. This explains the photosynthetic growth of these two mutants. The results are discussed in terms of evolution of the type II RCs and their secondary electron donors. PMID- 22305914 TI - Use of the levonorgestrel-releasing intrauterine system in renal transplant recipients: a retrospective case review. AB - Our objective was to report on the use of the levonorgestrel-releasing intrauterine system (LNG-IUS, Mirena(r)) in renal transplant recipients. A retrospective case review was done to identify renal transplant recipients for whom a LNG-IUS had been inserted. All of the women had been seen in the Gynecology Department, Beaumont Hospital, during the period 2000 to 2010. Parameters including age, year of transplantation, indication for insertion, duration of use, discontinuation and complications were documented. The main outcome measure was discontinuation of the LNG-IUS due to pelvic infection. Eleven women were identified who had undergone renal transplantation and were using the LNG-IUS. The mean duration of use was 38 (range 1-84) months. Four women were using the LNG-IUS for contraception and seven were using it for the treatment of menorrhagia, either alone or in conjunction with endometrial ablative procedures. One woman discontinued use in order to conceive. There were no unplanned pregnancies. There were no documented cases of pelvic infection in women using the device. Renal transplant recipients have a critical need for safe and effective contraception. The use of the LNG-IUS has been avoided in the patients due to the theoretical risk of intrauterine device-related pelvic infection in immune-suppressed patients. However, on the basis of our results, we believe that it is acceptable to use the LNG-IUS in renal transplant recipients for both contraception and for the treatment of menorrhagia as the theoretical risk of infection in these immune-suppressed patients does not appear to be increased. PMID- 22305915 TI - Missing IUD and utilization of fluoroscopy for management: a case report. AB - INTRODUCTION: A missing intrauterine device (IUD) poses challenges in diagnosis and treatment. Extrauterine placement of IUDs may cause difficulty in localization. We report a case where use of fluoroscopy just prior to laparoscopic intervention to remove the missing IUD was beneficial. CASE: This case report involves a 35-year-old woman who was diagnosed with a missing thread 2 years after insertion of a levonorgestrel IUD (Mirena). Initial diagnostic workup consisting of abdominal X-ray, an ultrasound and diagnostic laparoscopy failed to localize the IUD. We performed an office pelvic ultrasound which confirmed that an IUD was present but could not specifically localize the IUD in the pelvic or abdominal cavity. Hence, we utilized fluoroscopy just prior to laparoscopy to localize and remove the missing device and allow its removal. CONCLUSION: Various imaging modalities aid in detecting a missing IUD, but proper selection of fluoroscopy helped to localize extrauterine placement of an IUD device. We suggest that utilization of this imaging method just prior to laparoscopy may be of value in selected cases. PMID- 22305916 TI - Plan B, One Step not taken: politics trumps science yet again. PMID- 22305917 TI - A randomized controlled trial of different buccal misoprostol doses in mifepristone medical abortion. AB - BACKGROUND: An 800-mcg dose of buccal misoprostol following mifepristone has been shown to be highly effective in terminating pregnancies through 63 days since the last menstrual period (LMP) (B. Winikoff, I.G. Dzuba, M.D. Creinin, et al., Two distinct oral routes of misoprostol in mifepristone medical abortion: a randomized controlled trial. Obstet Gynecol 2008; 112: 1303-1310). However, a two 200-mcg misoprostol pill option would simplify administration, and potentially reduce costs and increase women's satisfaction. This study compares a 400-mcg dose (Group I) to an 800-mcg dose (Group II) of buccal misoprostol. STUDY DESIGN: Eligible and consenting women requesting medical termination of early pregnancy (n=1122) were randomized and instructed to take misoprostol 36 to 48 h after taking 200 mg mifepristone. Follow-up visits occurred 12 to 15 days after mifepristone administration. RESULTS: Ninety-six percent of women in both groups had successful abortions. Women in Group I experienced significantly less vomiting and fever/chills than women in Group II. Ninety-six percent of women in both groups found the procedure very satisfactory or satisfactory. CONCLUSIONS: Four hundred micrograms of buccal misoprostol is as effective as the standard 800 mcg dose in terminating pregnancies up to 63 days LMP and reduces side effects. PMID- 22305918 TI - Intraoperative use of clevidipine in a patient with von Hippel-Lindau disease with associated pheochromocytoma. PMID- 22305919 TI - Fate of large structural allograft for treatment of severe uncontained glenoid bone deficiency. AB - BACKGROUND: Structural allografts have been used for management of large defects of the glenoid. We describe a surgical technique for graft preparation and the radiographic and clinical results of a series of patients using this technique. MATERIALS AND METHODS: In 19 consecutive patients, a polymethyl methacrylate mold was used to shape a single graft from a fresh-frozen femoral head to press fit within the glenoid defect. We evaluated the clinical and radiographic results with a minimum 2-year follow-up or until revision to another total shoulder replacement. RESULTS: Six patients showed more than 50% resorption of the graft. Four of these six patients also had less than 50% graft incorporation, and these findings were associated with a less favorable clinical outcome. In 3 of 6 cases in which poly-L-lactic acid bioresorbable screws were used, a significant giant cell reaction was noted at the time of revision surgery. Seven of nine patients with metal screw fixation had bent, broken, or worn screws because of graft collapse and contact with the prosthetic humeral head. Four of the five revision cases that were converted to a reverse total shoulder replacement had sufficient bone incorporation and volume of bone to allow for secure glenoid and screw fixation. CONCLUSION: The surgical technique described is useful in creation of a well-fitting graft. The amount of bone resorption and bone incorporation and clinical outcome have wide variability. In those cases where revision was performed with another total shoulder replacement, there was sufficient bone incorporation and sufficient bone mass to allow component fixation. PMID- 22305920 TI - Evaluation of footprint contact area and pressure using a triple-row modification of the suture-bridge technique for rotator cuff repair. AB - BACKGROUND: Studies suggest that arthroscopic repair techniques may have high recurrence rates for larger rotator cuff tears. A more anatomic repair may improve the success rate when performing arthroscopic rotator cuff repair. We hypothesized that a triple-row modification of the suture-bridge technique for rotator cuff repair would result in significantly more footprint contact area and pressure between the rotator cuff and the humeral tuberosity. MATERIALS AND METHODS: Eighteen ovine infraspinatus tendons were repaired using 1 of 3 simulated arthroscopic techniques: a double-row repair, the suture-bridge technique, and a triple-row repair. The triple-row repair technique is a modification of the suture-bridge technique that uses an additional reducing anchor between the medial and lateral rows. Six samples were tested per group. Pressure-indicating film was used to measure the footprint contact area and pressure after each repair. RESULTS: The triple-row repair resulted in significantly more rotator cuff footprint contact area and contact pressure compared with the double-row technique and the standard suture-bridge technique. No statistical difference in contact area or contact pressure was found between the double-row technique and the suture-bridge technique. CONCLUSION: The triple row technique for rotator cuff repair results in significantly more footprint contact area and contact pressure compared with the double-row and standard suture-bridge techniques. This more anatomic repair may improve the healing rate when performing arthroscopic rotator cuff repair. PMID- 22305921 TI - Reinfection rates after 1-stage revision shoulder arthroplasty for patients with unexpected positive intraoperative cultures. AB - BACKGROUND: Recent studies have detailed the significance of indolent infections in revision shoulder arthroplasty, but little information is available to guide treatment strategies regarding patients with positive cultures without overt signs of infection. The primary purpose of this study was to determine recurrence rates of infection for patients undergoing revision shoulder arthroplasty who were not treated for infection but had positive intraoperative cultures. MATERIALS AND METHODS: We retrospectively reviewed the results of 17 patients undergoing revision of a failed shoulder joint replacement with at least 1 positive intraoperative culture who were not treated for infection because of limited signs of infection before or at the time of revision surgery. These patients underwent 1-stage revision surgery without an extended intravenous antibiotic regimen. RESULTS: The recurrence rate of infection for the 17 patients was 5.9%. The most common pathogen cultured at revision surgery was Propionibacterium acnes (10 of 17 [56%]), followed by coagulase-negative Staphylococcus species (6 of 17 [35%]). CONCLUSION: We found that low-virulence and clinically unexpected infections treated with 1-stage revision have a low risk for recurrent infection. This study suggests that intensive antimicrobial treatment strategies may not be necessary to reduce recurrent infections in patients with positive intraoperative cultures, without overt clinical signs of infection before or during the revision surgery. PMID- 22305922 TI - Evaluating quantitative methods for measuring plasmid copy numbers in single cells. AB - The life of plasmids is a constant battle against fluctuations: failing to correct copy number fluctuations can increase the plasmid loss rate by many orders of magnitude, as can a failure to more evenly divide the copies between daughters at cell division. Plasmids are therefore long-standing model systems for stochastic processes in cells, much thanks to the efforts of Kurt Nordstrom to whose memory this issue is dedicated. Here we analyze a range of experimental methods for measuring plasmid copy numbers in single cells, focusing on challenges, trade-offs, and necessary experimental controls. In particular we analyze published and unpublished strategies to infer copy numbers from expression of plasmid-encoded reporters, direct labeling of plasmids with fluorescent probes or DNA binding proteins fused to fluorescent reporters, PCR based methods applied to single cell lysates, and plasmid-specific replication arrest. We conclude that no method currently exists to measure plasmid copy numbers in single cells, and that most methods are overwhelmed by various types of experimental noise. We also discuss how accurate methods can be developed. PMID- 22305923 TI - Impaired executive functions in subjects with frequent nightmares as reflected by performance in different neuropsychological tasks. AB - Nightmare disorder is a prevalent parasomnia characterized by vivid and highly unpleasant dream experiences during night time sleep. The neural background of disturbed dreaming was proposed to be associated with impaired prefrontal and fronto-limbic functioning during REM sleep. We hypothesized that the impaired prefrontal and fronto-limbic functioning in subjects with frequent nightmares would be reflected at the behavioral level during waking tasks as well. 35-35 Subjects with frequent nightmares and matched controls participated in Study 1, involving an Emotional Go/NoGo, an Emotional Stroop task, and a Verbal Fluency task. Nightmare subjects exhibited longer reaction times in the Emotional Go/NoGo and Emotional Stroop tasks. Moreover, they committed more perseveration errors and showed less fluent word generation in the Verbal Fluency task. Nightmare subjects showed an overall slowing irrespective of the valence of the stimuli. While the effects of sleep quality and waking anxiety were associated to these deficits in some cases, these factors could not solely explain the difference between the two groups. In Study 2, 17 subjects with frequent nightmares and 18 controls were compared by a Color-word and an Emotional, block design Stroop task in order to avoid the slow effects of emotional interference potentially caused by previous items. Nightmare subjects were characterized by an overall slowing in the Emotional Stroop task, irrespective of the valence of the stimuli. In the Color-word Stroop task, nightmare subjects were not significantly slower in comparison with controls. Our results suggest that individuals with frequent nightmares are impaired in executive tasks involving the suppression of task irrelevant semantic representations. PMID- 22305924 TI - Dual-tasking alleviated sleep deprivation disruption in visuomotor tracking: an fMRI study. AB - Effects of dual-responding on tracking performance after 49-h of sleep deprivation (SD) were evaluated behaviorally and with functional magnetic resonance imaging (fMRI). Continuous visuomotor tracking was performed simultaneously with an intermittent color-matching visual detection task in which a pair of color-matched stimuli constituted a target and non-matches were non targets. Tracking error means were binned time-locked to stimulus onset of the detection task in order to observe changes associated with dual-responding by comparing the error during targets and non-targets. Similar comparison was made with fMRI data. Our result showed that despite a significant increase in the overall tracking error post SD, from 20 pixels pre SD to 45 pixels post SD, error decreased to a minimum of about 25 pixels 0-6s after dual-response. Despite an overall reduced activation post SD, greater activation difference between targets and non-targets was found post SD in task-related regions, such as the left cerebellum, the left somatosensory cortex, the left extrastriate cortex, bilateral precuneus, the left middle frontal gyrus, and the left motor cortex. Our results suggest that dual-response helps to alleviate performance impairment usually associated with SD. The duration of the alleviation effect was on the order of seconds after dual-responding. PMID- 22305925 TI - Effects of saccadic bilateral eye movements on memory in children and adults: an exploratory study. AB - The effects of saccadic bilateral (horizontal) eye movements on true and false memory in adults and children were investigated. Both adults and children encoded lists of associated words in the Deese-Roediger-McDermott paradigm followed by a test of recognition memory. Just prior to retrieval, participants were asked to engage in 30s of bilateral vs. vertical vs. no eye movements. For studied information, the results for adults replicated previous work; bilateral eye movements were demonstrated to increase the accuracy of memory by increasing the hit rate and reducing the false alarm rate for related and unrelated recognition test lures. The results for children also indicated an improvement in memory accuracy, and like adults, was due to both an increase in the hit rate and a reduction in the false alarm rate. In spite of these similarities, the effects of bilateral eye movements differed between adults and children for critical unstudied words; i.e., those associated with the theme of the list. Only in adults did, bilateral eye movements reduce associative false memories; children did not show a reduction in false memory for critical associates. This produced a dissociation between the effects of eye movements on associative false memory as a function of age. The results are discussed from a developmental perspective in terms of potential mechanisms underlying true and false memory. PMID- 22305926 TI - Heparanase accelerates the proliferation of both hepatocytes and endothelial cells early after partial hepatectomy. AB - BACKGROUND AND AIMS: Heparanase (HPSE) is an endo-beta-D-glucuronidase, which cleaves heparan sulfate in the extracellular matrix (ECM) and has pro-angiogenic and pro-proliferative properties. The aim of this investigation was to study the effect of HPSE on hepatocytes and endothelial cells (EC) during liver regeneration. METHODS: Following 70% hepatectomy (PHP), rats were injected daily with 1-50MUg HPSE/rat. Liver samples were stained with H&E and anti bromodeoxyuridine (BrdU) antibody. mRNAs of hepatocyte growth factor (HGF), stem cell factor, tumor necrosis factor (TNF)-alpha, interleukin(IL)-6, and cyclinD1 were tested by real-time qPCR. Matrix metalloproteinases (MMPs) were tested by gel zymography. RESULTS: Compared to the saline control, HPSE increased hepatocyte proliferation 24h, 48h and 72h after PHP, with the maximal effect found at 24h with 50MUg HPSE (40.9+/-2.5% vs. 8.6+/-4.3%, p<0.01 for BrdU staining; 5.5+/-0.9% vs. 0.8+/-0.5%, p<0.05 for mitosis). Proliferation of the sinusoidal and the portal vein radical ECs was also increased (p<0.05). HPSE caused a twofold increase in cyclinD1 mRNA (p<0.05) and in pro-MMP-9 levels (p<0.05). HPSE at all doses also caused significant reductions of TNF-alpha mRNA (p<0.05) and IL-6 mRNA, and no change in HGF mRNA. CONCLUSIONS: HPSE enhances liver regeneration by inducing proliferation of hepatocytes and both sinusoidal and vascular ECs. Since the effect of HPSE on hepatocytes occurred earlier than that observed in ECs, this effect is not related to HPSE's effect on ECs. The mechanism of HPSE action is probably indirect and is mediated by HPSE-dependent ECM cleavage and the release of pre-existing enzymes. PMID- 22305927 TI - Differential expression patterns of MMPs and their role in the invasion of epithelial premalignant tumors and invasive cutaneous squamous cell carcinoma. AB - Co-expression of several members of the matrix metalloproteinase (MMP) family is characteristic of human malignant tumors. MMP-2, MMP-9, TIMP-2, and MT1-MMP are thought to be involved in the process of destruction of basement membranes and stromal invasion by neoplastic epithelial cells. In this study, we investigated the expression and role of MMPs in cutaneous oncogenesis. Tissue microarray consisting of 62 squamous cell carcinomas (SCC), 32 Bowen's disease (BD) samples, 25 normal epidermis samples were obtained for the study. MMP-2,-9, MT1-MMP and TIMP-2 proteins were examined by immunohistochemical staining and mRNA level was detected by quantitative RT-PCR in fresh tissues consisting of 5 cutaneous SCCs and paired normal epidermis samples. Gelatinase activity of MMP-2 and MMP-9 was investigated by gelatin zymography and protein levels of MT1-MMP and TIMP-2 were measured by western blot in 2 human SCC cell lines. The invasive property was evaluated with invasion assays using Transwell filters. SCC exhibited significantly increased MMP-2, MT1-MMP and decreased TIMP-2 mRNA and protein expression compared to that of the normal epithelium. Immunohistochemical staining revealed that MT1-MMP was strongly expressed on the invasive front of SCCs, whereas BD exhibited higher expression around the dyskeratotic cells in the epithelium. In comparison with the expression observed in BD, SCC exhibited significantly increased MMP-2 expression. In addition, high MMP-2 and MT1-MMP expression and low TIMP-2 expression had a significant positive correlation with the invasiveness of SCC cell lines in vitro. Our results revealed significantly increased MT1-MMP and MMP-2 expression and decreased TIMP-2 expression in cutaneous SCC, and the expression correlated with the invasiveness of SCC cell lines. Therefore, the expression of these factors in cutaneous tumors may serve as an indicator of tumor aggressiveness and invasion. PMID- 22305928 TI - A dynamic perspective of RNAi library development. AB - Shortly after the dissertation of the mechanism of RNA interference (RNAi), various RNAi libraries for invertebrates, plants or mammals that enable loss-of function genetic screens on a genome-wide scale have been developed. Joint academic and industrial effort has led to the commercial launch of many of these libraries and this field is expected to continuously evolve at incredible speed. This article comparatively reviews the principles and applications of different RNAi libraries: from earlier synthetic to recent lentiviral RNAi libraries. The unique properties and limitations of each library will be important references for instigators to choose a particular library for their specific application. PMID- 22305929 TI - Statistical and methodological issues in microbicide trial design. AB - Microbicide trials aim to measure the effect of a microbicide in reducing the risk of acquiring human immunodeficiency virus. Such trials present a number of challenging issues from design and conduct through to analysis and reporting. This begins with the initial identification of the target trial population. Prevention trials need to identify those at risk of human immunodeficiency virus infection. This can be more difficult in the general population compared with treatment trials that can target specific patient groups who have a confirmed diagnosis of the disease of interest. Consequently, microbicide trial participants will inevitably be recruited who are never at risk of HIV infection. In this chapter we outline the main features of microbicide trial design, key issues during conduct and analysis, and discuss the challenges specific to these types of clinical trials. PMID- 22305930 TI - The AC8 IgG3 monoclonal anti-cholesterol antibody modulates uptake and presentation of antigens for T cell activation. AB - Natural anti-cholesterol antibodies (ACHAs) exist in mammalian species, moreover their level sensitively changes in pathological situations, such as atherosclerosis or HIV infection. The conditions of their production and functional role, however, still remained ill defined. Recently we developed IgG3 type monoclonal ACHAs that selectively react with 'clustered cholesterol' of live immune cells, such as membrane microdomains (lipid rafts and caveolas). These antibodies inhibited HIV-1 infection of Th cells and macrophages by remodeling the HIV-1 receptor/coreceptor distribution in the plasma membrane of target cells. As a novel modulatory effect, here we show that the AC8 IgG3 monoclonal anti-cholesterol antibody (mACHA), but not the AC9 IgM mACHA, spontaneously bind to all professional APCs, such as murine macrophages (Mfs) or bone marrow derived dendritic cells (DCs) and B lymphocytes. Upon binding, AC8 mAb remarkably enhanced the efficiency of yeast uptake by macrophages, but not the uptake of OVA Ig immune complexes by DCs. Binding to B lymphoma APCs, AC8 mAb remodeled their surface membrane by microclustering rafts and recruiting MHC-II and the CD80 costimulators to common microdomains. The modulated APCs induced an enhanced activation signaling (higher Ca(2+)-signals and NFAT1 activation) in Th cells conjugated with them, relative to untreated APCs. The results presented herein highlight the modulatory potential of the IgG3 type AC8 mAb on both innate and adaptive effector cell functions. PMID- 22305931 TI - Why human pemphigoid autoantibodies do not trigger disease by the passive transfer into mice? AB - The recapitulation of disease features in animals by the transfer of patient autoantibodies has been used to demonstrate the autoimmune nature of several diseases. Failure of disease induction by the passive transfer of autoantibodies has been assigned to a limited cross-reactivity of the autoantibodies with the murine tissue. However, the possibility that the passively transferred "inflammatory" patient autoantibodies may not be able to unfold their pathogenic potential due to restricted Fc-dependent effector functions has not yet been systematically explored. In this study we analyze the interaction of patients' autoantibodies with murine complement and granulocytes. Bullous pemphigoid is a blistering disease associated with autoantibodies, which are thought to induce subepidermal blistering by activating complement and granulocytes. The passive transfer of patients autoantibodies failed to induce skin blistering in wild type mice. The cross-reactivity of pemphigoid autoantibodies with murine antigens was analyzed in silico, ex vivo and by the passive transfer of IgG in vivo. Complement-fixing ability of patients' autoantibodies was evaluated by complement binding test. Granulocyte activation was assessed by reactive oxygen species production assay and the cryosection model. We have found that although pemphigoid autoantibodies bound to murine skin in vitro and in vivo, they showed a lower capacity to fix murine complement and a reduced ability to activate murine granulocytes when compared with human complement and cells, respectively. These results indicate that for disease models using the passive transfer of patient autoantibodies, their interaction with the innate factors of the host should be optimized to match the human situation. PMID- 22305932 TI - Suppression of mast cell degranulation through a dual-targeting tandem IgE-IgG Fc domain biologic engineered to bind with high affinity to FcgammaRIIb. AB - Mast cells and basophils play a central role in allergy, asthma, and anaphylaxis, as well as in non-allergic inflammatory, neurological and autoimmune diseases. Allergen-mediated cross-linking of IgE bound to FcepsilonRI leads to cellular activation, and the low-affinity Fc receptor FcgammaRIIb is a key inhibitor of subsequent degranulation. FcgammaRIIb, when coengaged with FcepsilonRI via allergen bound to IgE, stimulates ITIM domain-mediated inhibitory signaling that efficiently suppresses mast cell and basophil activation. To assess the therapeutic potential of directed coengagement of FcepsilonRI and FcgammaRIIb in the absence of FcepsilonRI crosslinking, we developed a fusion protein comprising the coupled Fc domains of murine IgE and human IgG1. As a key functional component of this tandem Fcepsilon-Fcgamma biologic, we engineered its IgG1 Fc domain to bind to human FcgammaRIIb with 100-fold enhanced affinity relative to native IgG1 Fc. Using mast cells from mice transgenic for human FcgammaRIIb, we show that this tandem Fc binds with high affinity to murine FcepsilonRI and human FcgammaRIIb on mast cells, triggers phosphorylation of FcgammaRIIb, and inhibits FcepsilonRI-dependent calcium mobilization. Control tandem Fc biologics containing a native IgG1 Fc domain or lacking binding to Fcgamma receptors were markedly less active, demonstrating that the affinity-optimized tandem Fc can inhibit degranulation through stimulation of FcgammaRIIb signaling as well as through competition with allergen-IgE immune complex for FcepsilonRI binding. We propose that in the context of a fully human tandem Fc biologic, high-affinity coengagement of FcepsilonRI and FcgammaRIIb has potential as a novel therapy for allergy and other mast cell and basophil-mediated pathologies. PMID- 22305933 TI - Decrease of the lumpectomy cavity volume after whole-breast irradiation affects small field boost planning. AB - To determine whether small field boost (SFB) replanning is necessary when the lumpectomy cavity (LPC) decreases during whole-breast irradiation (WBI) and what parameters might predict a change in the SFB plan. Forty patients had computed tomography (CT) simulation (CT1) within 60 days of surgery and were resimulated (CT2) after 37.8-41.4 Gy for SFB planning. A 3-field photon plan and a single en face electron plan were created on both CTs and compared. In the 26 patients who had a >=5 cm(3) and a >=25% decrease in lumpectomy cavity volume (LCV) between CT scans, the SFB plan using photons was different in terms of normal breast tissue volume irradiated (BTV) (p < 0.001), and field dimensions (p < 0.001). In 20/35 patients, the energy or field size changed for electron plans on CT2, but no tested characteristics predicted for a change. Less BTV was irradiated using electrons than photons in 29% (CT1) to 37% (CT2). SFB replanning needs to be individualized to each patient because of the variety of factors that can impact dosimetric planning. Replanning is recommended when using 3-field photons if the patient has experienced a >=5 cm(3) and a >=25% decrease in LCV during WBI. Some patients may benefit from electron SFB replanning but no tested characteristics reliably predict those who may benefit the most. The amount of BTV irradiated is less with electrons than in photon plans and this has the potential to improve cosmesis, a clinically important outcome in breast-conserving therapy. PMID- 22305934 TI - Design, synthesis and biological evaluation of novel 2-methylpyrimidine-4-ylamine derivatives as inhibitors of Escherichia coli pyruvate dehydrogenase complex E1. AB - As potential inhibitors of Escherichia coli pyruvate dehydrogenase complex E1 (PDHc E1), a series of novel 2-methylpyrimidine-4-ylamine derivatives were designed based on the structure of the active site of PDHc E1 and synthesized using 'click chemistry'. Their inhibitory activity in vitro against PDHc E1 and fungicidal activity were examined. Some of these compounds such as 3g, 3l, 3n, 3o, and 5b demonstrated to be effective inhibitors of PDHc E1 from E. coli and exhibited antifungal activity. SAR analysis indicated that both, the inhibitory potency against E. coli PDHc E1 and the antifungal activity of title compounds, could be increased greatly by optimizing substituent groups in the compounds. The structures of substituent group in 5-position on the 1,2,3-triazole and 4 position on the benzene ring in title compounds were found to play a pivotal role in both above-mentioned biological activities. Amongst all the compounds, compound 5b with iodine in the 5-position of 1,2,3-triazole and with nitryl group in the 4-position of benzene ring acted as the best inhibitor against PDHc E1 from E. coli. It was also found to be the most effective compound with higher antifungal activity against Rhizoctonia solani and Botrytis cinerea at the dosage of 100 MUg mL(-1). Therefore, in this study, compound 5b was used as a lead compound for further optimization. PMID- 22305935 TI - Contact lenses in ocular therapeutics. AB - Drug delivery is a difficult task in the field of ocular therapeutics. Owing to the physiological and anatomical constraints of the eye, it is difficult to obtain the correct therapeutic concentration of a drug at the required site of action. This has led to clinicians recommending frequent dosing, which has resulted in noncompliance by patients and decreased cost effectiveness. To overcome these barriers, scientists have explored novel ocular delivery systems, such as in situ gels, ocuserts, nanoparticles and liposomes. A particularly novel form of such a delivery system are contact lenses, which are thin, curved plastic disks that are designed to cover the cornea and which cling to the surface of the eye owing to surface tension. In this article, we describe the introductory literature on ocular delivery using contact lenses, their classification and manufacturing process, and recent advances on drug delivery techniques using such lenses. PMID- 22305936 TI - Auto-associative amphiphilic polysaccharides as drug delivery systems. AB - Self-assembly of amphiphilic polysaccharides provides a positive outlook for drug delivery systems without the need for solvents or surfactants. Various polymeric amphiphilic polysaccharides undergo intramolecular or intermolecular associations in water. This type of association, promoted by hydrophobic segments, led to the formation of various drug delivery systems such as micelles, nanoparticles, liposomes and hydrogels. Here, we review a selection of the most important amphiphilic polysaccharides used as drug delivery systems and their pharmaceutical applications. Attention focuses on amphiphilic chitosan owing to its unique properties such as excellent biocompatibility, non-toxicity and antimicrobial and bioadhesive properties. PMID- 22305937 TI - Reactions and enzymes in the metabolism of drugs and other xenobiotics. AB - In this article, we offer an overview of the compared quantitative importance of biotransformation reactions in the metabolism of drugs and other xenobiotics, based on a meta-analysis of current research interests. Also, we assess the relative significance the enzyme (super)families or categories catalysing these reactions. We put the facts unveiled by the analysis into a drug discovery context and draw some implications. The results confirm the primary role of cytochrome P450-catalysed oxidations and UDP-glucuronosyl-catalysed glucuronidations, but they also document the marked significance of several other reactions. Thus, there is a need for several drug discovery scientists to better grasp the variety of drug metabolism reactions and enzymes and their consequences. PMID- 22305938 TI - Roles of the Y-family DNA polymerase Dbh in accurate replication of the Sulfolobus genome at high temperature. AB - The intrinsically thermostable Y-family DNA polymerases of Sulfolobus spp. have revealed detailed three-dimensional structure and catalytic mechanisms of trans lesion DNA polymerases, yet their functions in maintaining their native genomes remain largely unexplored. To identify functions of the Y-family DNA polymerase Dbh in replicating the Sulfolobus genome under extreme conditions, we disrupted the dbh gene in Sulfolobus acidocaldarius and characterized the resulting mutant strains phenotypically. Disruption of dbh did not cause any obvious growth defect, sensitivity to any of several DNA-damaging agents, or change in overall rate of spontaneous mutation at a well-characterized target gene. Loss of dbh did, however, cause significant changes in the spectrum of spontaneous forward mutation in each of two orthologous target genes of different sequence. Relative to wild-type strains, dbh(-) constructs exhibited fewer frame-shift and other small insertion-deletion mutations, but exhibited more base-pair substitutions that converted G:C base pairs to T:A base pairs. These changes, which were confirmed to be statistically significant, indicate two distinct activities of the Dbh polymerase in Sulfolobus cells growing under nearly optimal culture conditions (78-80 degrees C and pH 3). The first activity promotes slipped-strand events within simple repetitive motifs, such as mononucleotide runs or triplet repeats, and the second promotes insertion of C opposite a potentially miscoding form of G, thereby avoiding G:C to T:A transversions. PMID- 22305939 TI - Noninvasive in vitro measurement of pig-blood d-glucose by using a microwave cavity sensor. AB - We have developed an electromagnetic microwave cavity sensor based on the resonant frequency shift for real time measurement of the glycemia in pig blood. We could determine the concentration of d-glucose in pig blood in the range of 150-550mg/dl at the resonance frequency near 4.75GHz with a bandwidth of 300MHz. The change in the d-glucose concentration in blood brings microwave reflection coefficient S(11) changes of about 6.26dB and resonance frequency shifts of about 11.25MHz due to the electromagnetic interaction between the cavity resonator and the blood filled plastic tube inserted into the cavity. This proposed system provides a unique approach for real time noninvasive and contactless glucose monitoring. PMID- 22305940 TI - Determinants of uncontrolled dyslipidaemia among adult type 2 diabetes in Malaysia: the Malaysian Diabetes Registry 2009. AB - Numerous studies with compelling evidence had shown a clear relationship between dyslipidaemia and cardiovascular (CV) events in patients with diabetes mellitus. This was an observational study based on secondary data from the online registry database Adult Diabetes Control and Management (ADCM) looking into the determinants of uncontrolled dyslipidaemia in type 2 diabetes mellitus patients. Independent predictors were identified using multivariate logistic regression. A total of 303 centres (289 health clinics, 14 hospitals) contributed a total of 70,889 patients (1972 or 2.8% patients were from hospital). About thirty eight percent were reported to have dyslipidaemia. There were 40.7% patients on lipid lowering agents and of those above age 40 years old, only 38.1% of them were on a statin. Malay ethnicity and younger age groups (<50 years old) were two major determinants of uncontrolled LDL-C, TG and HDL-C. Female gender and uncontrolled blood pressure were determinants of uncontrolled LDL-C, and poor glycaemic control was related independently to high TG. This study has highlighted the suboptimal management of diabetic dyslipidaemia in Malaysia. Pharmacological treatment of dyslipidaemia could be more effective. Healthcare stakeholders in this country, especially in the primary care, have to recognize these shortfalls and take immediate remedial measures. PMID- 22305941 TI - Pharmacoepidemiological profiles of oral hypoglycemic agents among 28,773 Chinese patients with diabetes. AB - AIMS: This study examined the rates of discontinuation of Oral Hypoglycemic Agents (OHAs) in diabetes patients, and to evaluate the associations between discontinuation of OHAs, socioeconomic status and the number of comorbidities. METHODS: A cohort study from January 2004 to June 2007 was conducted and followed up through December 2007. We included all primary care clinics in one large territories of Hong Kong involving 28,773 Chinese diabetes patients. Multivariate regression analyses controlled for age, gender, payment status (fee-payers vs. fee waivers; fee-waivers represented those less able to pay for consultation fees and were regarded as having lower socioeconomic status), service type delivered by the clinics, district of residence, visit type (new vs. follow-up), the number of comorbidities and the drug class (sulphonylureas vs. biguanide vs. combination therapy). RESULTS: 9.9% discontinued their medications within 180 days of their prescriptions. Fee waivers (adjusted odds ratio [AOR] for fee payers=0.81, 95% C.I. 0.73-0.89, p<0.001) and the absence of comorbidities (AOR for >=one morbidity=0.59-0.62, p<0.001) were associated with medication discontinuation. CONCLUSIONS: Diabetes patients with lower ability to pay and without comorbidities were significantly associated with OHAs discontinuation. They should be the target groups for medication counseling programmes. PMID- 22305942 TI - Glucose sensor excludes hypoglycaemia as cause of death. AB - The cause of death can be difficult to verify post-mortem in unexpected deaths in patients with Type 1 diabetes. This report describes an unexpected death in a 44 year-old man with Type 1 diabetes treated with sensor-augmented pump therapy. Continuous glucose monitoring data proved useful in determining the cause of death. PMID- 22305943 TI - Polyprenols from the needles of Taxus chinensis var. mairei. AB - Polyprenols with various pharmacological activities were first isolated from Taxus chinensis var. mairei, which is native to China, and were identified by a high performance liquid chromatography/mass spectrometry (HPLC/MS), (1)H nuclear magnetic resonance ((1)H NMR), (13)C NMR and infrared (IR) spectroscopy. The taxus polyprenols (TPs) had two maxima of polyprenol-17 and polyprenol-21 and different from polyprenols distributed in other plant species. A reversed-phase HPLC method with a simple gradient elution was established, and the proposed combined peak area method for the quantification of polyprenols was verified. The analysis indicated that TPs were present in the old needles at levels as high as 3% and that T. chinensis var. mairei could be an alternative botanical source for the extraction of polyprenols. PMID- 22305944 TI - Anti-HBV activities of Streblus asper and constituents of its roots. AB - The extracts from leaves, heartwood, barks and roots of the Streblus asper were investigated for anti-HBV activities, separately. The results suggested that the MeOH extracts of the heartwood, barks, and roots exhibited good anti-HBV activities. Further investigations displayed that ethyl acetate and n-butanol soluble parts of their MeOH extracts showed more significant anti-HBV activities. Moreover, a new lignan, together with 11 known compounds, was isolated from n butanol-soluble part of MeOH extract of the roots of S. asper. The structures were elucidated by spectroscopic methods, including 1D NMR ((1)H NMR, (13)C NMR), 2D NMR (HMQC, HMBC) and HR-EI-MS experiments. Compounds 1-3 were evaluated for their anti-HBV activities. Honokiol showed significant anti-HBV activity with IC(50) values of 3.14MUM and 4.74MUM for HBsAg and HBeAg with no cytotoxicity respectively, while lamivudine (3TC, positive control) exhibited weak anti-HBV activity with IC(50) values of 11.81MUM and 25.80MUM for HBsAg and HBeAg respectively. PMID- 22305945 TI - Cytotoxic ceramides and glycerides from the roots of Livistona chinensis. AB - A 70% ethanol extract of the roots of Livistona chinensis has been investigated, led to the isolation of 13 compounds, including a new ceramide, (2S,3S,4R,9Z)-2 [(2R)-2-hydroxytricosanoylamino]-9-octadecene-1,3,4-triol (2), a new glycosyl ceramide, 1-O-beta-D-glucopyranosyl-(2S,3S,4R,9Z)-2-[(2R)-2 hydroxydocosanoylamino]-9-octadecene-1,3,4-triol (3), three new monoacylglycerols, 1-(34-hydroxytetratriacontanoyl)-sn-glycerol (9), 1-[nonadeca (9Z,12Z)-dienoyl]-sn-glycerol (10), and 1-[12-hydroxypentatriaconta-(13E,15Z) dienoyl]-sn-glycerol (11), a new diacylglycerol, 1-(heptadeca-6Z,9Z-dienoyl)-3 (octadeca-6Z,9Z,12Z-trienoyl)-sn-glycerol (12), as well as a new diacylglycerol aminoglycoside, 1-octadecanoyl-2-nonadecanoyl-3-O-(6-amino-6-deoxy)-beta-D glucopyranosyl-sn-glycerol (13). The structures of new compounds were elucidated, based on spectroscopic, zymologic and chemical methods. Among the compounds tested, compounds 3, 4 and 13 showed significantly antiproliferative effects against the human tumor cell lines (K562, HL-60, HepG2, and CNE-1) with the IC50 of 10-65 MUM. To our knowledge, this is first report of the occurrence of ceramides and acylglycerols in the genus Livistona. PMID- 22305946 TI - Therapeutic landscapes and postcolonial theory: a theoretical approach to medical tourism. AB - This paper draws on two conceptual frameworks, therapeutic landscapes and postcolonial theory, to discuss aspects of medical tourism not addressed in extant literature. Building on the intersection between postcolonial and therapeutic landscapes scholarship, it highlights inequalities related to the production of national therapeutic landscapes located in postcolonial regions as well as their discursive (re)positioning as medical tourism destinations. As a framework, therapeutic landscapes can facilitate an understanding of medical tourism sites as curative spaces which combine modern and alternative forms of medicine with travel and leisure. Postcolonial theory critiques the economic, moral and cultural tensions emerging from the intersection between corporations that provide cheaper and more attractive medical services, and the nations on the periphery struggling to offer high medical standards that may not be accessible to their own local populations. In an effort to enhance scholarship on medical tourism, these conceptual frameworks are offered as points of departure, rather than sites of arrival, through which critical dialog on medical tourism can be sustained and broadened. PMID- 22305947 TI - Social support, volunteering and health around the world: cross-national evidence from 139 countries. AB - High levels of social capital and social integration are associated with self rated health in many developed countries. However, it is not known whether this association extends to non-western and less economically advanced countries. We examine associations between social support, volunteering, and self-rated health in 139 low-, middle- and high-income countries. Data come from the Gallup World Poll, an internationally comparable survey conducted yearly from 2005 to 2009 for those 15 and over. Volunteering was measured by self-reports of volunteering to an organization in the past month. Social support was based on self-reports of access to support from relatives and friends. We started by estimating random coefficient (multi-level) models and then used multivariate logistic regression to model health as a function of social support and volunteering, controlling for age, gender, education, marital status, and religiosity. We found statistically significant evidence of cross-national variation in the association between social capital variables and self-rated health. In the multivariate logistic model, self-rated health were significantly associated with having social support from friends and relatives and volunteering. Results from stratified analyses indicate that these associations are strikingly consistent across countries. Our results indicate that the link between social capital and health is not restricted to high-income countries but extends across many geographical regions regardless of their national-income level. PMID- 22305948 TI - Practitioner opinions on health promotion interventions that work: opening the 'black box' of a linear evidence-based approach. AB - While attempts are being made to improve health promotion by following a linear Evidence-Based (EB) approach, the actors involved are aware that the quality of health promotion is not just a matter of supplying 'evidence-based' interventions to local practitioners, but the result of a situated coproduction process that depends on many factors. This paper explores what constitutes an intervention that works from the perspective of health promotion professionals (HPP), and how, according to them, the development and implementation of interventions should be improved. We interviewed 81 HPPs about the use of 10 health promotion interventions at 30 Municipality Health Services in The Netherlands. The HPPs described an intervention that works as something that produces its intended effects after being realized in a local situation. Interventions are realized by combining elements of a supplied intervention (e.g. a theory, artefacts) with elements that are situated in the local context (e.g. funding, local network). Interventions that are transferred contain implicit assumptions about local contexts, but it is often unclear what precisely constitutes an intervention and what is assumed of local contexts. An intervention that works is a situated configuration of aligned elements. A linear EB approach depends on the realization of the local circumstances in which 'evidence based' interventions can work. Various strategies are possible for approximating such circumstances, but the core assumption that the configuration that is realized in practice is similar to the 'evidence based' intervention seems unrealistic for most health promotion in The Netherlands. Under such circumstances, attention should shift from central quality assurance to the system of actors and the distributed actions and heterogeneous learning processes that together add up to interventions that work. PMID- 22305949 TI - Contextual influences on the development of obesity in children: a case study of UK South Asian communities. AB - OBJECTIVE: An advocated approach to childhood obesity prevention research is the use of local community knowledge to inform intervention development. This paper demonstrates the value of accessing such local knowledge, and discusses how this information fits with existing conceptual models of childhood obesity. METHODS: A series of 9 focus groups were run in 2007 with 68 local community stakeholders (including parents, school staff, community leaders and health and local government representatives) from 8 South Asian communities in Birmingham, UK to explore perceptions of factors contributing to the development of childhood obesity. RESULTS: Perceptions of causal influences were grouped into several contexts, from the individual to the macro-level, that influence diet and physical activity. Specific cultural contextual data emerged that may explain decisions around physical activity and food intake of children within these communities. Assumptions made about South Asian communities were frequently contested. CONCLUSIONS: In order to truly understand the contextual influences on childhood obesity in target communities, it is necessary to access knowledge from local community members. Existing conceptual models of childhood obesity do not bring the role of cultural factors to the fore, but this context needs to be explicitly considered in the development of childhood obesity interventions. PMID- 22305950 TI - MRI atrophy of the caudate nucleus and slower walking speed in the elderly. AB - Cerebral white matter lesions are associated with poorer motor performances in the elderly, but the role of gray matter atrophy remains largely unknown. We investigated the cross-sectional relation between brain regional gray matter volumes and walking speed over 6m in the 3C-Dijon study, a large population-based study of community-dwelling persons aged 65 years and over (N=1623). Regional gray matter volumes were obtained using an automated anatomical labeling parcellation method. Multivariable analyses were performed using a semi-Bayes approach. After adjustment for potential confounders, persons who walked slower had a smaller volume of basal ganglia (regression coefficient [beta]=0.054, standard error [SE]=0.028, p=0.05). In more detailed analyses, the volume of the caudate nucleus had a preponderant role on this association (beta=0.049, SE=0.019, p=0.009), and walking speed decreased progressively with the volume of the caudate nucleus (p for linear trend<0.001). These results underline the role of gray matter subcortical structures, in particular of the caudate nucleus, in the age-related decline of motor performances among community-dwelling elderly subjects. PMID- 22305951 TI - Preparation of fixed mouse brains for MRI. AB - In fixed mouse brain magnetic resonance images, a high prevalence of fixation artifacts have been observed. Of more than 1700 images of fixed brains acquired at our laboratory, fixation artifacts were present in approximately 30%. In this study, two of these artifacts are described and their causes are identified. A hyperintense rim around the brain is observed when using perfusates reconstituted from powder and delivered at a high flow rate. It is proposed that these perfusion conditions cause blockage of the capillary beds and an increase in pressure that ruptures the vessels, resulting in a blister of liquid below the dura mater. Secondly, gray-white matter contrast inversion is observed when too short a fixation time or too low a concentration of fixative is used, resulting in inadequate fixation. The deleterious consequences of these artifacts for quantitative data analysis are discussed, and precautions for their prevention are provided. PMID- 22305952 TI - Nonlinear denoising and analysis of neuroimages with kernel principal component analysis and pre-image estimation. AB - We investigate the use of kernel principal component analysis (PCA) and the inverse problem known as pre-image estimation in neuroimaging: i) We explore kernel PCA and pre-image estimation as a means for image denoising as part of the image preprocessing pipeline. Evaluation of the denoising procedure is performed within a data-driven split-half evaluation framework. ii) We introduce manifold navigation for exploration of a nonlinear data manifold, and illustrate how pre image estimation can be used to generate brain maps in the continuum between experimentally defined brain states/classes. We base these illustrations on two fMRI BOLD data sets - one from a simple finger tapping experiment and the other from an experiment on object recognition in the ventral temporal lobe. PMID- 22305953 TI - Construction of a neuroanatomical shape complex atlas from 3D MRI brain structures. AB - Brain atlas construction has attracted significant attention lately in the neuroimaging community due to its application to the characterization of neuroanatomical shape abnormalities associated with various neurodegenerative diseases or neuropsychiatric disorders. Existing shape atlas construction techniques usually focus on the analysis of a single anatomical structure in which the important inter-structural information is lost. This paper proposes a novel technique for constructing a neuroanatomical shape complex atlas based on an information geometry framework. A shape complex is a collection of neighboring shapes - for example, the thalamus, amygdala and the hippocampus circuit - which may exhibit changes in shape across multiple structures during the progression of a disease. In this paper, we represent the boundaries of the entire shape complex using the zero level set of a distance transform function S(x). We then re-derive the relationship between the stationary state wave function psi(x) of the Schrodinger equation [formula in text] and the eikonal equation [formula in text] satisfied by any distance function. This leads to a one-to-one map (up to scale) between psi(x) and S(x) via an explicit relationship. We further exploit this relationship by mapping psi(x) to a unit hypersphere whose Riemannian structure is fully known, thus effectively turn psi(x) into the square-root of a probability density function. This allows us to make comparisons - using elegant, closed-form analytic expressions - between shape complexes represented as square root densities. A shape complex atlas is constructed by computing the Karcher mean psi-(x) in the space of square-root densities and then inversely mapping it back to the space of distance transforms in order to realize the atlas shape. We demonstrate the shape complex atlas computation technique via a set of experiments on a population of brain MRI scans including controls and epilepsy patients with either right anterior medial temporal or left anterior medial temporal lobectomies. PMID- 22305954 TI - Analysis of automated methods for spatial normalization of lesioned brains. AB - Normalization of brain images is a crucial step in MRI data analysis, especially when dealing with abnormal brains. Although cost function masking (CFM) appears to successfully solve this problem and seems to be necessary for patients with chronic stroke lesions, this procedure is very time consuming. The present study sought to find viable, fully automated alternatives to cost function masking, such as Automatic Lesion Identification (ALI) and Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL). It also sought to quantitatively assess, for the first time, Symmetrical Normalization (SyN) with constrained cost function masking. The second aim of this study was to investigate the normalization process in a group of drug-resistant epileptic patients with large resected regions (temporal lobe and amygdala) and in a group of stroke patients. A dataset of 500 artificially generated lesions was created using ten patients with brain-resected regions (temporal lobectomy), ten stroke patients and twenty five-healthy subjects. The results indicated that although a fully automated method such as DARTEL using New Segment with an extra prior (the mean of the white matter and cerebro-spinal fluid) obtained the most accurate normalization in both patient groups, it produced a shrinkage in lesion volume when compared to Unified Segmentation with CFM. Taken together, these findings suggest that further research is needed in order to improve automatic normalization processes in brains with large lesions and to completely abandon manual, time consuming normalization methods. PMID- 22305955 TI - The past, present and future of social neuroscience: a European perspective. AB - This review provides an overview of the field of social neuroscience from a European perspective and focuses mainly on outlining research topics which originated in European laboratories. After a brief historical synopsis of the emergence of this young field, the most relevant findings related to the investigation of the neural networks underlying our capacity to understand the minds of others are summarized. More specifically, three routes of social cognition are distinguished: (1) our capacity to mentalize, or to infer intentions and beliefs of others, (2) our capacity to mimic and understand other's motor actions, and (3) our capacity to empathize, or to share and understand the feelings of others. More recent studies focusing on social emotions such as love, compassion, revenge or our sense of fairness will be discussed linking the field of social neuroscience to the even younger field of neuroeconomics, with the focus on the study of human social interactions using game theoretical paradigms. Finally, the use of a multi-method and multi disciplinary research approach combining genetic, pharmacological, computational and developmental aspects is advocated and future directions for the study of interactive minds are discussed. PMID- 22305956 TI - Different prognostic impact of the tissue Doppler-derived E/e' ratio on mortality in Chagas cardiomyopathy patients with heart failure. AB - BACKGROUND: Risk assessment of Chagas cardiomyopathy patients is essential for clinical decision making. The ratio of the ratio of early transmitral velocity to tissue Doppler mitral annular early diastolic velocity (E/e') is a powerful predictor of adverse outcome in patients with heart failure. However, its prognostic value remains to be established in the setting of Chagas cardiomyopathy. This study investigated the effect of E/e' on mortality according to different degrees of left ventricular (LV) systolic function in patients with Chagas cardiomyopathy. METHODS: The study prospectively enrolled 232 patients (143 men) with Chagas cardiomyopathy (mean age, 48 +/- 12 years). End points were death or cardiac transplantation. RESULTS: During a mean follow-up of 3.4 years, 107 patients had an adverse cardiac event, with an overall events rate of 13.2/year. Cox proportional hazards model was used with New York Heart Association functional class, LV ejection fraction, right ventricular function, indexed left atrial volume, E/e' ratio, and the statistical interaction term between E/e' ratio and LV ejection fraction. The effect of E/e' ratio on mortality depended on the degree of LV systolic dysfunction. An increasing E/e' ratio was a strong predictor of outcome in patients with mild to moderate LV dysfunction but was inversely associated with mortality in patients with severe systolic dysfunction. CONCLUSION: This study demonstrated the role of the interaction between LV ejection fraction and E/e' ratio in predicting prognosis in Chagas cardiomyopathy patients. The E/e' ratio had a stronger prognostic value in patients with mild and moderate LV dysfunction and was inversely associated with mortality in patients with advanced systolic heart failure. PMID- 22305957 TI - Diffusion tensor imaging in attention deficit/hyperactivity disorder: a systematic review and meta-analysis. AB - Diffusion tensor imaging (DTI) allows in vivo examination of the microstructural integrity of white matter brain tissue. A systematic review and quantitative meta analysis using GingerALE were undertaken to compare current DTI findings in patients with ADHD and healthy controls to further unravel the neurobiological underpinnings of the disorder. Online databases were searched for DTI studies comparing white matter integrity between ADHD patients and healthy controls. Fifteen studies met inclusion criteria. Alterations in white matter integrity were found in widespread areas, most consistently so in the right anterior corona radiata, right forceps minor, bilateral internal capsule, and left cerebellum, areas previously implicated in the pathophysiology of the disorder. Current literature is critically discussed in terms of its important methodological limitations and challenges, and guidelines for future DTI research are provided. While more research is needed, DTI proves to be a promising technique, providing new prospects and challenges for future research into the pathophysiology of ADHD. PMID- 22305958 TI - Radiographic changes after lung stereotactic ablative radiotherapy (SABR)--can we distinguish recurrence from fibrosis? A systematic review of the literature. AB - BACKGROUND: Changes in lung density on computed tomography (CT) are common after stereotactic ablative radiotherapy (SABR) and can confound the early detection of recurrence. We performed a systematic review to describe post-SABR findings on computed tomography (CT) and positron-emission tomography (PET), identify imaging characteristics that predict recurrence and propose a follow-up imaging algorithm. METHODS: A systematic review was conducted of studies providing detailed radiologic descriptions of anatomic and metabolic lung changes after SABR. Our search returned 824 studies; 26 met our inclusion criteria. Data are presented according to PRISMA guidelines. RESULTS: Acute changes post-SABR predominantly appear as consolidation or ground glass opacities. Late changes often demonstrate a modified conventional pattern of fibrosis, evolving beyond 2years after treatment. Several CT features, including an enlarging opacity, correlate with recurrence. Although PET SUVmax may rise immediately post-SABR, an SUVmax?5 carries a high predictive value of recurrence. CONCLUSIONS: CT density changes are common post-SABR. The available evidence suggests that recurrent disease should be suspected if high-risk CT changes are seen with SUVmax?5 on PET. Further studies are needed to validate the predictive values of such metrics, and for advanced analysis of CT changes to allow early detection of potentially curable local recurrence. PMID- 22305959 TI - Calcineurin and Akt expression in hypertrophied bladder in STZ-induced diabetic rat. AB - Diabetes causes significant increases in bladder weight but the natural history and underlying mechanisms are not known. In this study, we observed the temporal changes of detrusor muscle cells (DMC) and the calcineurin (Cn) and Akt expressions in detrusor muscle in the diabetic rat. Male Sprague-Dawley rats were divided into 3 groups: streptozotocin-induced diabetics, 5% sucrose-induced diuretics, and age-matched controls. The bladders were removed 1, 2, or 9weeks after disease induction and the extent of hypertrophy was examined by bladder weights and cross sectional area of DMC. Cn and Akt expression were evaluated by immunoblotting. Both diabetes and diuresis caused significant increases in bladder weight. The mean cross sectional areas of DMC were increased in both diabetic and diuretic animals 1, 2, or 9weeks after disease induction. The expression levels of both the catalytic A (CnA) and regulatory B (CnB) subunits of Cn were increased at 1 and 2weeks, but not at 9weeks. Expression of Akt was similar among control, diabetic, and diuretic rat bladder at all time points. In conclusion, diabetes and diuresis induce similar hypertrophy of detrusor muscle during the first 9weeks, indicating that bladder hypertrophy in the early stage of diabetes is in response to the presence of increased urine output in diabetes. Our results suggest that the Cn, but not the Akt signaling pathway may be involved in the development of bladder hypertrophy. PMID- 22305960 TI - Characterization of isolates of Citrus tristeza virus by sequential analyses of enzyme immunoassays and capillary electrophoresis-single-strand conformation polymorphisms. AB - Citrus tristeza virus (CTV) is the causal agent of tristeza disease, which is one of the most devastating diseases of citrus crops worldwide. This paper describes a method for the rapid detection and genotyping of naturally spreading CTV isolates. This method uses ELISA or dot-blot immunological tests to detect trees infected with CTV. The reaction wells or membrane spots for which there is a positive reaction are sequentially treated by (i) washing and elution of viral RNA from the trapped samples, (ii) one-step synthesis of cDNA and PCR and (iii) automated fluorescence-based capillary electrophoresis single-strand conformation polymorphism (CE-SSCP) analysis of amplification products. Comparative CE-SSCP results are presented for CTV RNA extracted directly from infected leaves and ELISA plates or from membranes. In the analyses of all of these RNA samples, the p18, p27 and p23 CTV genes were targeted for amplification. Specific profiles of forward and reverse strands were obtained from a group of eight CTV isolates collected in Sicily, each with distinct biological characteristics, which were analyzed using the conventional two-step procedure (immunological detection followed by CE-SSCP molecular characterization after RNA isolation) or in a continuous process of ELISA/CE-SSCP or dot-blot/CE-SSCP starting from infected plant material. The combined method is simple, highly sensitive and reproducible, thus allowing the processing of numerous field samples for a variety of epidemiological needs. The sequential processing of an ELISA or dot-blot/ELISA followed by CE-SSCP is expected to allow the rapid detection of recent CTV infections along with the simultaneous characterization of the genetic diversity and structure of the population of newly invading CTV. PMID- 22305961 TI - Susceptibility of the PER.C6 cell line for infection with clinical human respiratory syncytial virus isolates. AB - Human respiratory syncytial virus (HRSV) is one of the most important agents causing upper respiratory infection in infants. The susceptibility of the PER.C6 cell line for infection with clinical HRSV strains was investigated. During the HRSV season of 2006/2007 in Belgium, 90 isolates were inoculated into the PER.C6 and HEp-2 cells and viral growth was evaluated by quantification of the extracellular viral RNA concentration. Initially, viral growth of HRSV strains was observed after 7 days of inoculation in the PER.C6 cells, demonstrated by an increase in HRSV RNA levels. However, HRSV strains that were selected for continued propagation in the PER.C6 cells no longer seemed to replicate, which was reflected by consecutive decreasing viral RNA levels. Several approaches that were investigated to improve the efficiency of infection of clinical HRSV isolates in the PER.C6 cells, such as the influence of rotation and centrifugation of the virus inoculum into the cells were unsuccessful. In contrast, when clinical HRSV strains were inoculated in the HEp-2 cells substantial virus stocks could be produced and the virus could be propagated up to infectious titers of 5 logPFU per ml. In conclusion, the PER.C6 cell line was not permissive for persistent HRSV infection in our experiments and did not support long term production of large virus stocks at high titers. This possibly limits the use of this cell line for many in vitro applications using HRSV, e.g. plaque or virus yield reduction assays or the preparation of virus stocks for in vivo challenge experiments or in vitro vaccine production. PMID- 22305962 TI - Mechanisms and predictors of mitral regurgitation after high-risk myocardial infarction. AB - BACKGROUND: Mitral regurgitation (MR) has been associated with adverse outcomes after myocardial infarction (MI). Without structural valve disease, functional MR has been related to left ventricular (LV) remodeling and geometric deformation of the mitral apparatus. The aims of this study were to elucidate the mechanistic components of MR after high-risk MI and to identify predictors of MR progression during follow-up. METHODS: The Valsartan in Acute Myocardial Infarction Echo substudy prospectively enrolled 610 patients with LV dysfunction, heart failure, or both after MI. MR at baseline, 1 month, and 20 months was quantified by mapping jet expansion in the left atrium in 341 patients with good-quality echocardiograms. Indices of LV remodeling, left atrial size, and diastolic function and parameters of mitral valve deformation, including tenting area, coaptation depth, anterior leaflet concavity, annular diameters, and contractility, were assessed and related to baseline MR. The progression of MR was further analyzed, and predictors of worsening among the baseline characteristics were identified. RESULTS: Tenting area, coaptation depth, annular dilatation, and left atrial size were all associated with the degree of baseline MR. Tenting area was the only significant and independent predictor of worsening MR; a tenting area of 4 cm(2) was a useful cutoff to identify worsening of MR after MI and moderate to severe MR after 20 months. CONCLUSIONS: Increased mitral tenting and larger mitral annular area are determinants of MR degree at baseline, and tenting area is an independent predictor of progression of MR after MI. Although LV remodeling itself contributes to ischemic MR, this influence is directly dependent on alterations in mitral geometry. PMID- 22305964 TI - Gross morphological changes in thylakoid membrane structure are associated with photosystem I deletion in Synechocystis sp. PCC 6803. AB - Cells of Synechocystis sp. PCC 6803 lacking photosystem I (PSI-less) and containing only photosystem II (PSII) or lacking both photosystems I and II (PSI/PSII-less) were compared to wild type (WT) cells to investigate the role of the photosystems in the architecture, structure, and number of thylakoid membranes. All cells were grown at 0.5MUmol photons m(-2)s(-1). The lumen of the thylakoid membranes of the WT cells grown at this low light intensity were inflated compared to cells grown at higher light intensity. Tubular as well as sheet-like thylakoid membranes were found in the PSI-less strain at all stages of development with organized regular arrays of phycobilisomes on the surface of the thylakoid membranes. Tubular structures were also found in the PSI/PSII-less strain, but these were smaller in diameter to those found in the PSI-less strain with what appeared to be a different internal structure and were less common. There were fewer and smaller thylakoid membrane sheets in the double mutant and the phycobilisomes were found on the surface in more disordered arrays. These differences in thylakoid membrane structure most likely reflect the altered composition of photosynthetic particles and distribution of other integral membrane proteins and their interaction with the lipid bilayer. These results suggest an important role for the presence of PSII in the formation of the highly ordered tubular structures. PMID- 22305963 TI - The innate immune response to products of phospholipid peroxidation. AB - Lipid peroxidation occurs in the context of many physiological processes but is greatly increased in various pathological situations. A consequence of phospholipid peroxidation is the generation of oxidation-specific epitopes, such as phosphocholine of oxidized phospholipids and malondialdehyde, which form neo self determinants on dying cells and oxidized low-density lipoproteins. In this review we discuss evidence demonstrating that pattern recognition receptors of the innate immune system recognize oxidation-specific epitopes as endogenous damage-associated molecular patterns, allowing the host to identify dangerous biological waste. Oxidation-specific epitopes are important targets of both cellular and soluble pattern recognition receptors, including toll-like and scavenger receptors, C-reactive protein, complement factor H, and innate natural IgM antibodies. This recognition allows the innate immune system to mediate important physiological house keeping functions, for example by promoting the removal of dying cells and oxidized molecules. Once this system is malfunctional or overwhelmed the development of diseases, such as atherosclerosis and age related macular degeneration is favored. Understanding the molecular components and mechanisms involved in this process, will help the identification of individuals with increased risk of developing chronic inflammation, and indicate novel points for therapeutic intervention. This article is part of a Special Issue entitled: Oxidized phospholipids-their properties and interactions with proteins. PMID- 22305965 TI - The biochemistry and function of pannexin channels. AB - Three family members compose the pannexin family of channel-forming glycoproteins (Panx1, Panx2 and Panx3). Their primary function is defined by their capacity to form single-membrane channels that are regulated by post-translational modifications, channel intermixing, and sub-cellular expression profiles. Panx1 is ubiquitously expressed in many mammalian tissues, while Panx2 and Panx3 appear to be more restricted in their expression. Paracrine functions of Panx1 as an ATP release channel have been extensively studied and this channel plays a key role, among others, in the release of "find-me" signals for apoptotic cell clearance. In addition Panx1 has been linked to propagation of calcium waves, regulation of vascular tone, mucociliary lung clearance, taste-bud function and has been shown to act like a tumor suppressor in gliomas. Panx1 channel opening can also be detrimental, contributing to cell death and seizures under ischemic or epileptic conditions and even facilitating HIV-1 viral infection. Panx2 is involved in differentiation of neurons while Panx3 plays a role in the differentiation of chondrocytes, osteoblasts and the maturation and transport of sperm. Using the available Panx1 knockout mouse models it has now become possible to explore some of its physiological functions. However, given the potential for one pannexin to compensate for another it seems imperative to generate single and double knockout mouse models involving all three pannexins and evaluate their interplay in normal differentiation and development as well as in malignant transformation and disease. This article is part of a Special Issue entitled: The communicating junctions, roles and dysfunctions. PMID- 22305966 TI - PKCeta is a negative regulator of AKT inhibiting the IGF-I induced proliferation. AB - The PI3K-AKT pathway is frequently activated in human cancers, including breast cancer, and its activation appears to be critical for tumor maintenance. Some malignant cells are dependent on activated AKT for their survival; tumors exhibiting elevated AKT activity show sensitivity to its inhibition, providing an Achilles heel for their treatment. Here we show that the PKCeta isoform is a negative regulator of the AKT signaling pathway. The IGF-I induced phosphorylation on Ser473 of AKT was inhibited by the PKCeta-induced expression in MCF-7 breast adenocarcinoma cancer cells. This was further confirmed in shRNA PKCeta-knocked-down MCF-7 cells, demonstrating elevated phosphorylation on AKT Ser473. While PKCeta exhibited negative regulation on AKT phosphorylation it did not alter the IGF-I induced ERK phosphorylation. However, it enhanced ERK phosphorylation when stimulated by PDGF. Moreover, its effects on IGF-I/AKT and PDGF/ERK pathways were in correlation with cell proliferation. We further show that both PKCeta and IGF-I confer protection against UV-induced apoptosis and cell death having additive effects. Although the protective effect of IGF-I involved activation of AKT, it was not affected by PKCeta expression, suggesting that PKCeta acts through a different route to increase cell survival. Hence, our studies show that PKCeta provides negative control on AKT pathway leading to reduced cell proliferation, and further suggest that its presence/absence in breast cancer cells will affect cell death, which could be of therapeutic value. PMID- 22305967 TI - Neurotechnology: Summa technologiae. PMID- 22305968 TI - Age-related differences in the brain areas outside the classical language areas among adults using category decision task. AB - Older adults perform much like younger adults on language. This similar level of performance, however, may come about through different underlying brain processes. In the present study, we evaluated age-related differences in the brain areas outside the typical language areas among adults using a category decision task. Our results showed that similar activation patterns were found in classical language processing areas across the three age groups although regional lateralization indices in Broca's and Wernicke's areas decreased with age. The greatest differences, however, among the three groups were found primarily in the brain areas not associated with core language functioning including the hippocampus, middle frontal gyrus, ventromedial frontal cortex, medial superior parietal cortex and posterior cingulate cortex. Therefore, the non-classical language areas may exhibit an age-related difference between three age groups while the subjects show a similar activation pattern in the core, primary language processing during a semantic decision task. PMID- 22305969 TI - Metabolomics: a tool for early detection of toxicological effects and an opportunity for biology based grouping of chemicals-from QSAR to QBAR. AB - BASF has developed a Metabolomics database (MetaMap((r)) Tox) containing approximately 500 data rich chemicals, agrochemicals and drugs. This metabolome database has been built based upon 28-day studies in rats (adapted to OECD 407 guideline) with blood sampling and metabolic profiling after 7, 14 and 28 days of test substance treatment. Numerous metabolome patterns have been established for different toxicological targets (liver, kidney, thyroid, testes, blood, nervous system and endocrine system) which are specific for different toxicological modes of action. With these patterns early detection of toxicological effects and the underlying mechanism can now be obtained from routine studies. Early recognition of toxicological mode of action will help to develop new compounds with a more favourable toxicological profile and will also help to reduce the number of animal studies necessary to do so. Thus this technology contributes to animal welfare by means of reduction through refinement (2R), but also has potential as a replacement method by analyzing samples from in vitro studies. With respect to the REACH legislation for which a large number of animal studies will need to be performed, one of the most promising methods to reduce the number of animal experiments is grouping of chemicals and read-across to those which are data rich. So far mostly chemical similarity or QSAR models are driving the selection process of chemical grouping. However, "omics" technologies such as metabolomics may help to optimize the chemical grouping process by providing biologically based criteria for toxicological equivalence. "From QSAR to QBAR" (quantitative biological activity relationship). PMID- 22305970 TI - Integrating pathway-based transcriptomic data into quantitative chemical risk assessment: a five chemical case study. AB - The traditional approach for performing a chemical risk assessment is time and resource intensive leading to a limited number of published assessments on which to base human health decisions. In comparison, most contaminated sites contain chemicals without published reference values or cancer slope factors that are not considered quantitatively in the overall hazard index calculation. The integration of transcriptomic technology into the risk assessment process may provide an efficient means to evaluate quantitatively the health risks associated with data poor chemicals. In a previous study, female B6C3F1 mice were exposed to multiple concentrations of five chemicals that were positive for lung and/or liver tumor formation in a two-year rodent cancer bioassay. The mice were exposed for a period of 13 weeks and the target tissues were analyzed for traditional histological and organ weight changes and transcriptional changes using microarrays. In this study, the dose-response changes in gene expression were analyzed using a benchmark dose (BMD) approach and the responses grouped based on pathways. A comparison of the transcriptional BMD values with those for the traditional non-cancer and cancer apical endpoints showed a high degree of correlation for specific pathways. Many of the correlated pathways have been implicated in non-cancer and cancer disease pathogenesis. The results demonstrate that transcriptomic changes in pathways can be used to estimate non-cancer and cancer points-of-departure for use in quantitative risk assessments and have identified potential toxicity pathways involved in chemically induced mouse lung and liver responses. PMID- 22305971 TI - Celecoxib, a cyclooxygenase-2 inhibitor, potentiates the chemotherapic effect of vinorelbine in the medullary thyroid cancer TT cell line. AB - We analyzed the in vitro effects of celecoxib, a COX-2 inhibitor, and determined if celecoxib can sensitize a human MTC-derived cell line (TT) to chemotherapeutics. We found that celecoxib induced apoptosis in TT cells and decreased drug efflux by reducing the expression of MDR-1 mRNA, which codes for the drug efflux pump P-gp. We also observed that TT cells were 10-fold more resistant to doxorubicin than to vinorelbine, mimicking what can be observed in clinical practice. In addition, we found that the combination of celecoxib and vinorelbine, but not doxorubicin, induced a significant reduction in cell viability and a significant increase in apoptosis. In conclusion, we showed that celecoxib was able to enhance the chemotherapeutic effect of vinorelbine. A clinical trial exploring the in vivo activities of celecoxib in MTC patients who cannot benefit from available treatments would be desirable, taking into account the possible risks of cardiovascular effects of this drug. PMID- 22305972 TI - The role of endocannabinoids in gonadal function and fertility along the evolutionary axis. AB - Endocannabinoids are natural lipids able to bind to cannabinoid and vanilloid receptors. Their biological actions at the central and peripheral level are under the tight control of the proteins responsible for their synthesis, transport and degradation. In the last few years, several reports have pointed out these lipid mediators as critical signals, together with sex hormones and cytokines, in various aspects of animal and human reproduction. The identification of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in reproductive cells and tissues of invertebrates, vertebrates and mammals highlights the key role played by these endogenous compounds along the evolutionary axis. Here, we review the main actions of endocannabinoids on female and male reproductive events, and discuss the interplay between them, steroid hormones and cytokines in regulating fertility. In addition, we discuss the involvement of endocannabinoid signalling in ensuring a correct chromatin remodeling, and hence a good DNA quality, in sperm cells. PMID- 22305973 TI - Screening and identification of BSA bound ligands from Puerariae lobata flower by BSA functionalized Fe3O4 magnetic nanoparticles coupled with HPLC-MS/MS. AB - Puerariae lobata flower (Willdenow) has a long history used to treat alcoholic intoxication in China, which contains a series of isoflavones as its chief pharmacologically active constituents. In this study, bovine serum albumin (BSA) functionalized iron oxide magnetic nanoparticles (Fe3O4 MNPs) coupled with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) were used to screen and identify active compounds from ethanolic extract of P. lobata flower. Thirteen active isoflavones were screened and identified as glycitin (1), tectoridin (2), daidzin (3), 3'-methoxy daidzin (4), ononin (5), 3'-hydroxyl daidzein (6), tectorigenin (7), biochanin A (8), prunetin (9), genistein (10), 3' methoxy daidzein (11), irisolidone (12) and 5,7-dihydroxy-3',4' methylenedioxyisoflavone (13), while compounds 4, 6, 9, 11 and 13 were identified from this plant for the first time. Furthermore, the activity of each bound ligand was evaluated on-line. The results indicated that the binding affinities of compounds with BSA were highly dependent on chemical structures and the methoxylation and hydroxylation on B-ring could improve the activity. The effective method could be widely applied for rapid screening and identification of active compounds from complex mixtures. PMID- 22305974 TI - Obsessive compulsive disorder. AB - INTRODUCTION: Obsessions or compulsions that cause personal distress or social dysfunction affect about 1% of adult men and 1.5% of adult women. About half of adults with obsessive compulsive disorder (OCD) have an episodic course, whereas the other half have continuous problems. Prevalence in children and adolescents is 2.7%. The disorder persists in about 40% of children and adolescents at mean follow-up of 5.7 years. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of initial treatments for obsessive compulsive disorder in adults? What are the effects of initial treatments for obsessive compulsive disorder in children and adolescents? What are the effects of maintenance treatment for obsessive compulsive disorder in adults? What are the effects of maintenance treatment for obsessive compulsive disorder in children and adolescents? What are the effects of treatments for obsessive compulsive disorder in adults who have not responded to initial treatment with serotonin reuptake inhibitors (SRIs)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 43 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: addition of antipsychotics to serotonin reuptake inhibitors, behavioural therapy alone or with serotonin reuptake inhibitors, cognitive therapy or cognitive behavioural therapy (CBT) (alone or with serotonin reuptake inhibitors), electroconvulsive therapy, optimum duration of maintenance treatment, psychosurgery, serotonin reuptake inhibitors (citalopram, clomipramine, fluoxetine, fluvoxamine, paroxetine, or sertraline), and transcranial magnetic stimulation. PMID- 22305975 TI - Asthma and other recurrent wheezing disorders in children (chronic). AB - INTRODUCTION: Childhood asthma is the most common chronic paediatric illness. There is no cure for asthma but good treatment to palliate symptoms is available. Asthma is more common in children with a personal or family history of atopy, increased severity and frequency of wheezing episodes, and presence of variable airway obstruction or bronchial hyperresponsiveness. Precipitating factors for symptoms and acute episodes include infection, house dust mites, allergens from pet animals, exposure to tobacco smoke, and exercise. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of single-agent prophylaxis in children taking as needed inhaled beta(2) agonists for asthma? What are the effects of additional prophylactic treatments in childhood asthma inadequately controlled by standard dose inhaled corticosteroids? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 48 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: beta(2) agonists (long-acting), corticosteroids (inhaled standard or higher doses), leukotriene receptor antagonists (oral), omalizumab, and theophylline (oral). PMID- 22305976 TI - Menorrhagia. AB - INTRODUCTION: Menorrhagia limits normal activities, and causes anaemia in two thirds of women with objective menorrhagia (loss of 80 mL blood per cycle). Prostaglandin disorders may be associated with idiopathic menorrhagia, and with heavy bleeding due to fibroids, adenomyosis, or use of intrauterine devices (IUDs). Fibroids have been found in 10% of women with menorrhagia overall, and in 40% of women with severe menorrhagia; but half of women having a hysterectomy for menorrhagia are found to have a normal uterus. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments for menorrhagia? What are the effects of surgical treatments for menorrhagia? What are the effects of endometrial thinning before endometrial destruction in treating menorrhagia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations, such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 39 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following medical interventions: combined pill, danazol, etamsylate, gonadorelin analogues, intrauterine progesterone, non-steroidal anti-inflammatory drugs (NSAIDs), progestogens, and the following surgical interventions: dilatation and curettage, endometrial destruction, and hysterectomy. PMID- 22305977 TI - Behavioral effects of incomplete temporal lobe necrosis and cerebellar damage. PMID- 22305978 TI - Experimental and theoretical study on the 1:1 supramolecular complexes of formamide with adrenaline. AB - The electron transfer properties were investigated for supramolecular complexes of formamide (FA) with adrenaline (Ad) at graphite electrode and paraffine soaked graphite electrode using cyclic voltammetry (CV). The experimental results show that FA affected the electron transfer properties of Ad. The formed supramolecular complexes by hydrogen bond (H-bond) interaction between FA and Ad slowed down the diffusion ability of adrenaline, which makes it hard to donate electron and be oxidized. The H-bond interaction energies calculation for the supramolecular complexes of FA with Ad at MP2/6-311+G(d,p)//B3LYP/6-311+G(d,p) level have also been performed. The calculational results confirm the experimental fact that FA can form stable supramolecular complexes with Ad. PMID- 22305979 TI - Comparative analysis of the structural and expressional parameters of microRNA target genes. AB - MicroRNAs (miRNAs) generally pair with the 3'UTRs of their target mRNAs to repress gene expression. It has reported that miRNA targets (TGs) are longer and evolve more slowly than non-targets (NTGs). We confirmed the observation and also found novel structural and expressional characteristics of TGs. The length difference between TGs and NTGs was greatest for the 3'UTRs, although a difference was also observed for CDSs and introns. Widely expressed genes were shorter for both TGs and NTGs; however, TGs were significantly longer than NTGs in all ranges of expression. TGs were more likely than NTGs to be widely expressed, which might explain why TGs evolve more slowly than NTGs. Finally, we found that TG mRNAs have faster decay rates. In addition, the decay rate of a TG mRNA transcript was found to be positively correlated with the number or density of target sites located in that TG's mRNA transcript. PMID- 22305980 TI - Somatic mosaicism in two unrelated patients with X-linked chronic granulomatous disease characterized by the presence of a small population of normal cells. AB - X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency disease of phagocytes caused by mutations in the cytochrome b(558)beta (CYBB) gene. We, for the first time, detected somatic mosaicism in two unrelated male patients with X-CGD caused by de novo nonsense mutations (p.Gly223X and p.Glu462X) in the CYBB gene. In each patient, a small subset of granulocytes was normal in terms of respiratory burst (ROB) activity, gp91(phox) expression, and CYBB sequences. Cells with wild-type CYBB sequence were also detected in buccal swab specimens and in peripheral blood mononuclear cells. The normal cells were shown to be of the patient origin by fluorescent in situ hybridization analysis of X/Y chromosomes, and by HLA DNA typing. Two possible mechanisms for this somatic mosaicism were considered. The first is that the de novo disease-causing mutations in CYBB occurred at an early multicellular stage of embryogenesis with subsequent expansion of the mutated cells, leaving some unmutated cells surviving. The second possibility is that the de novo mutations occurred in oocytes which was followed by reversion of the mutations in a small subset of cells in early embryogenesis. PMID- 22305981 TI - Calculating phenotypic similarity between genes using hierarchical structure data based on semantic similarity. AB - Phenotypic similarity is correlated with a number of measures of gene function, such as relatedness at the level of direct protein-protein interaction. The phenotypic effect of a deleted or mutated gene, which is one part of gene annotation, has caught broad attention. However, there have been few measures to study phenotypic similarity with the data from Human Phenotype Ontology (HPO) database, therefore more analogous measures should be developed and investigated. We used five semantic similarity-based measures (Jiang and Conrath, Lin, Schlicker, Yu and Wu) to calculate the human phenotypic similarity between genes (PSG) with data from HPO database, and evaluated their accuracy with information of protein-protein interaction, protein complex, protein family, gene function or DNA sequence. Compared with the gene pairs that were random selected, the results of these methods were statistically significant (all P<0.001). Furthermore, we assessed the performance of these five measures by receiver operating characteristic (ROC) curve analysis, and found that most of them performed better than the previous methods. This work had proved that these measures based on semantic similarity for calculation of PSG were effective for hierarchical structure data. Our study contributes to the development and optimization of novel algorithms of PSG calculation and provides more alternative methods to researchers as well as tools and directions for PSG study. PMID- 22305982 TI - Does the growth temperature of a prokaryote influence the purine content of its mRNAs? AB - The formation and breaking of hydrogen bonds between nucleic acid bases are dependent on temperature. The high G+C content of organisms was surmised to be an adaptation for high temperature survival because of the thermal stability of G:C pairs. However, a survey of genomic GC% and optimum growth temperature (OGT) of several prokaryotes revoked any direct relation between them. Significantly high purine (R=A or G) content in mRNAs is also seen as a selective response for survival among thermophiles. Nevertheless, the biological relevance of thermophiles loading their unstable mRNAs with excess purines (purine-loading or R-loading) is not persuasive. Here, we analysed the mRNA sequences from the genomes of 168 prokaryotes (as obtained from NCBI Genome database) with their OGTs ranging from -5 degrees C to 100 degrees C to verify the relation between R-loading and OGT. Our analysis fails to demonstrate any correlation between R loading of the mRNA pool and OGT of a prokaryote. The percentage of purine-loaded mRNAs in prokaryotes is found to be in a rough negative correlation with the genomic GC% (r(2)=0.655, slope=-1.478, P<000.1). We conclude that genomic GC% and bias against certain combinations of nucleotides drive the mRNA-synonymous (sense) strands of DNA towards variations in R-loading. PMID- 22305983 TI - Genomic characteristics comparisons of 12 food-related filamentous fungi in tRNA gene set, codon usage and amino acid composition. AB - Filamentous fungi are widely exploited in food industry due to their abilities to secrete large amounts of enzymes and metabolites. The recent availability of fungal genome sequences has provided an opportunity to explore the genomic characteristics of these food-related filamentous fungi. In this paper, we selected 12 representative filamentous fungi in the areas of food processing and safety, which were Aspergillus clavatus, A. flavus, A. fumigatus, A. nidulans, A. niger, A. oryzae, A. terreus, Monascus ruber, Neurospora crassa, Penicillium chrysogenum, Rhizopus oryzae and Trichoderma reesei, and did the comparative studies of their genomic characteristics of tRNA gene distribution, codon usage pattern and amino acid composition. The results showed that the copy numbers greatly differed among isoaccepting tRNA genes and the distribution seemed to be related with translation process. The results also revealed that genome compositional variation probably constrained the base choice at the third codon, and affected the overall amino acid composition but seemed to have little effect on the integrated physicochemical characteristics of overall amino acids. The further analysis suggested that the wobble pairing and base modification were the important mechanisms in codon-anticodon interaction. In the scope of authors' knowledge, it is the first report about the genomic characteristics analysis of food-related filamentous fungi, which would be informative for the analysis of filamentous fungal genome evolution and their practical application in food industry. PMID- 22305984 TI - Loss of the Prader-Willi obesity syndrome protein necdin promotes adipogenesis. AB - We investigated the role of necdin during adipogenic differentiation. Necdin is one of several genes inactivated in children with Prader-Willi syndrome, who are predisposed to increased adiposity at the expense of lean mass. Necdin promotes neuronal and muscle differentiation and survival through interactions with a variety of proteins, including cell surface receptors, modifiers of protein stability, and transcription factors. In pre-adipocytes, necdin over-expression inhibits adipogenesis, while reducing necdin levels enhances adipogenic differentiation in tissue culture cells. We now directly demonstrate a role for necdin in inhibiting adipogenesis using cells derived from necdin deficient mice. PMID- 22305985 TI - Study on the age-dependent tissue expression of FUT1 gene in porcine and its relationship to E. coli F18 receptor. AB - Escherichia coli (E. coli) that produces adhesin F18 is the main pathogen responsible for porcine post-weaning diarrhea and edema disease. The receptor for E. coli F18 has not been described in pigs, however the alpha (1,2) fucosyltransferase (FUT1) gene on chromosome 6 has been proposed as a candidate. The objective of this study, therefore, was to investigate the relationship between FUT1 gene expression and E. coli F18 receptor in Sutai pigs of different ages (8-, 18-, 30- and 35-day-old). FUT1 gene expression was detected in 11 pig tissues with the highest level in lung, and expressed consistently at the four time points. In most tissues, FUT1 gene expression levels decreased from days 8 to 18, then continually increased on days 30 and 35, with expression around weaning time higher than that on day 8. Gene ontology and pathway analysis showed that FUT1 was involved in 32 biological processes, mainly those integral to the membrane, or involved in glycosylation, as well as regulation of binding, interestingly participating in three pathways related to glycosphingolipid biosynthesis. From this analysis and the high linkage disequilibrium between the FUT1 gene and the E. coli F18 receptor locus, we can speculate that higher expression of the FUT1 gene in small intestine is beneficial to the formation of receptors to the E. coli F18 strain and is related to the sensitivity to the pathogen. PMID- 22305986 TI - A diverse array of creatine kinase and arginine kinase isoform genes is present in the starlet sea anemone Nematostella vectensis, a cnidarian model system for studying developmental evolution. AB - Phosphagen (guanidino) kinases (PK) constitute a family of homologous phosphotransferases catalyzing the reversible transfer of the high-energy phosphoryl group of ATP to naturally occurring guanidine compounds. Prior work has shown that PKs can be phylogenetically separated into two distinct groups- an arginine kinase (AK) subfamily and a creatine kinase (CK) subfamily. The latter includes three CK isoforms- cytoplasmic CK (CyCK), mitochondrial CK (MiCK) and three-domain flagellar CK (fCK). In the present study we identified six unique PK genes from the draft genome sequence of the starlet sea anemone Nematostella vectensis, a well-known model organism for understanding metazoan developmental evolution. Using reverse transcription polymerase chain reaction (RTPCR) methods, full length cDNAs were amplified for all of these PKs. These cDNAs were cloned and expressed in Escherichia coli as 6x His-tagged fusion proteins. The six PKs were identified as the three typical CK isoforms (CyCK, MiCK and fCK), two unusual AKs (a two-domain AK (2DAK) and a three-domain AK (3DAK)) and a PK which phosphorylated arginine. The latter enzyme had a very low AK activity (its apparent V(max) value being less than 0.2% that of 3DAK), lacks several key residues necessary for AK enzyme activity, and was tentatively designated as AK1. As far as we know, this constitutes the first report of an AK with the three fused AK domains. The Bayesian tree suggested that the third domain of 3DAK likely evolved from the gene for domain 2 of typical two-domain AK found widely in cnidarians. Construction of phylogenetic trees and comparison of exon-intron organizations of their respective genes indicated that the N. vectensis three domain fCK and 3DAK evolved independently, and both enzymes are likely to be targeted to cell membranes since they have a myristoylation signal at their respective N-termini. These results complement prior work on other basal invertebrates showing that multiple CK and AK isoform genes were present at the dawn of the radiation of metazoans. The presence of isoform diversity in an organism lacking in structural complexity reflects an early imperative for targeting of PKs to particular cellular contexts such as muscle fibers, neurons, ciliated/flagellated epithelia and spermatozoa. PMID- 22305987 TI - Prevalence of hepatitis B virus (HBV) co-infection in HBV serologically-negative South African HIV patients and retrospective evaluation of the clinical course of mono- and co-infection. AB - OBJECTIVES: Hepatitis B virus (HBV) infection with undetectable hepatitis B surface antigen (HBsAg) has been reported in HIV patients, but the clinical significance is unknown. This study presents the prevalence of HBV DNA in HIV positive patients negative for all HBV serological markers and a retrospective evaluation of the clinical course of mono- and co-infection. METHODS: Of 502 HIV positive patients, 222 tested negative for HBsAg, antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc). An in house real-time PCR targeting the HBV S-region was used to quantify HBV DNA. HBV isolates were genotyped. Baseline demographic and clinical characteristics of HBV DNA-positive and HBV DNA-negative patients were described. Treatment outcomes of patients at 6, 12, and 24 months after initiation of antiretroviral therapy (ART) were summarized. RESULTS: HBV DNA was detected in 5.4% (12/222) of serologically negative patients. Mean HBV viral load was 5359.2 IU/ml (standard deviation (SD) +/-12 768.27). Eleven HBV isolates belonged to genotype A and one to genotype C. There were no significant differences in baseline characteristics or clinical course between the HBV DNA-positive and HBV DNA-negative groups. CONCLUSIONS: We found 5.4% of the HBV serologically-negative HIV-positive patients had low levels of HBV DNA. There were no significant differences in clinical outcome between the mono- and co-infected groups. PMID- 22305988 TI - Circular representation of human cortical networks for subject and population level connectomic visualization. AB - Cortical network architecture has predominantly been investigated visually using graph theory representations. In the context of human connectomics, such representations are not however always satisfactory because canonical methods for vertex-edge relationship representation do not always offer optimal insight regarding functional and structural neural connectivity. This article introduces an innovative framework for the depiction of human connectomics by employing a circular visualization method which is highly suitable to the exploration of central nervous system architecture. This type of representation, which we name a 'connectogram', has the capability of classifying neuroconnectivity relationships intuitively and elegantly. A multimodal protocol for MRI/DTI neuroimaging data acquisition is here combined with automatic image segmentation to (1) extract cortical and non-cortical anatomical structures, (2) calculate associated volumetrics and morphometrics, and (3) determine patient-specific connectivity profiles to generate subject-level and population-level connectograms. The scalability of our approach is demonstrated for a population of 50 adults. Two essential advantages of the connectogram are (1) the enormous potential for mapping and analyzing the human connectome, and (2) the unconstrained ability to expand and extend this analysis framework to the investigation of clinical populations and animal models. PMID- 22305989 TI - The intravascular susceptibility effect and the underlying physiology of fMRI. AB - In this article, I will first give a brief account of my work at MGH on characterizing the intravascular susceptibility effect. Then I will describe studies into the underlying physiology of BOLD-fMRI which has become of interest to my group in the following decade. I will touch issues such as signal source of BOLD fMRI, capillary recruitment, the elusive initial dip and others. PMID- 22305990 TI - The spatial distribution of age-related white matter changes as a function of vascular risk factors--results from the LADIS study. AB - White matter hyperintensities (WMH) are a frequent finding on brain MRI of elderly subjects, and have been associated with various risk factors, as well as with development of cognitive and functional impairment. While an overall association between WMH load and risk factors is well described, possible spatially restricted vulnerability remains to be established. The aim of this study was to investigate the spatial distribution of WMH in normally functioning elderly subjects. We introduce a voxel-based approach in which lesion probability is mapped as a function of clinical risk factors using logistic regression, and validate the method using simulated datasets. The method was then applied in a total of 605 participants of the LADIS study (age 74 +/- 5 years, all with WMH), and the location of manually delineated WMH was investigated after spatial normalisation. Particularly strong and widespread associations were found for age, gender and hypertension. Different distribution patterns were found for men and women. Further, increased probability was found in association with self reported alcohol and tobacco consumption, as well as in those with a history of migraine. It is concluded that the location of WMH is dependent on the risk factors involved pointing towards a regionally different pathogenesis and/or vulnerability of the white matter. PMID- 22305991 TI - Reactivation of visual cortex during memory retrieval: content specificity and emotional modulation. AB - Studies on memory retrieval suggest a reactivation of cortical regions engaged during encoding, such that visual or auditory areas reactivate for visual or auditory memories. The content specificity and any emotion dependency of such reactivations are still unclear. Because distinct visual areas are specialized in processing distinct stimulus categories, we tested for face and word specific reactivations during a memory task using functional magnetic resonance imaging (fMRI). Furthermore, because visual processing and memory are both modulated by emotion, we compared reactivation for stimuli encoded in a neutral or emotionally significant context. In the learning phase, participants studied pairs of stimuli that consisted of either a scene and a face, or a scene and a word. Scenes were either neutral or negative, but did not contain faces or words. In the test phase scenes were presented alone (one in turn), and participants indicated whether it was previously paired with a face, a word, or was new. Results from the test phase showed activation in a functionally defined face-responsive region in the right fusiform gyrus, as well as in a word-responsive region in the left inferior temporal gyrus, for scenes previously paired with faces and words, respectively. Reactivation tended to be larger in both the face- and word-responsive regions when the associated scene was negative as compared to neutral. However, relative to neutral context, the recall of faces and words paired with a negative context produced smaller activations in brain regions associated with social and semantic processing, respectively, as well as poorer memory performance overall. Taken together, these results support the idea of cortical memory reactivations, even at a content-specific level, and further suggest that emotional context may produce opposite effects on reactivations in early sensory areas and more elaborate processing in higher-level cortical areas. PMID- 22305992 TI - Steady-state responses in MEG demonstrate information integration within but not across the auditory and visual senses. AB - To form a unified percept of our environment, the human brain integrates information within and across the senses. This MEG study investigated interactions within and between sensory modalities using a frequency analysis of steady-state responses that are elicited time-locked to periodically modulated stimuli. Critically, in the frequency domain, interactions between sensory signals are indexed by crossmodulation terms (i.e. the sums and differences of the fundamental frequencies). The 3 * 2 factorial design, manipulated (1) modality: auditory, visual or audiovisual (2) steady-state modulation: the auditory and visual signals were modulated only in one sensory feature (e.g. visual gratings modulated in luminance at 6 Hz) or in two features (e.g. tones modulated in frequency at 40 Hz & amplitude at 0.2 Hz). This design enabled us to investigate crossmodulation frequencies that are elicited when two stimulus features are modulated concurrently (i) in one sensory modality or (ii) in auditory and visual modalities. In support of within-modality integration, we reliably identified crossmodulation frequencies when two stimulus features in one sensory modality were modulated at different frequencies. In contrast, no crossmodulation frequencies were identified when information needed to be combined from auditory and visual modalities. The absence of audiovisual crossmodulation frequencies suggests that the previously reported audiovisual interactions in primary sensory areas may mediate low level spatiotemporal coincidence detection that is prominent for stimulus transients but less relevant for sustained SSR responses. In conclusion, our results indicate that information in SSRs is integrated over multiple time scales within but not across sensory modalities at the primary cortical level. PMID- 22305993 TI - Gradient echo plural contrast imaging--signal model and derived contrasts: T2*, T1, phase, SWI, T1f, FST2*and T2*-SWI. AB - Gradient Echo Plural Contrast Imaging (GEPCI) is a post processing technique that, based on a widely available multiple gradient echo sequence, allows simultaneous generation of naturally co-registered images with various contrasts: T1 weighted, R2*=1/T2* maps and frequency (f) maps. Herein, we present results demonstrating the capability of GEPCI technique to generate image sets with additional contrast characteristics obtained by combing the information from these three basic contrast maps. Specifically, we report its ability to generate GEPCI-susceptibility weighted images (GEPCI-SWI) with improved SWI contrast that is free of T1 weighting and RF inhomogeneities; GEPCI-SWI-like images with the contrast similar to original SWI; T1f images that offer superior GM/WM matter contrast obtained by combining the GEPCI T1 and frequency map data; Fluid Suppressed T2* (FST2*) images that utilize GEPCI T1 data to suppress CSF signal in T2* maps and provide contrast similar to FLAIR T2 weighted images; and T2*-SWI images that combine SWI contrast with quantitative T2* map and offer advantages of visualizing venous structure with hyperintense T2* lesions (e.g. MS lesions). To analyze GEPCI images we use an improved algorithm for combining data from multi-channel RF coils and a method for unwrapping phase/frequency maps that takes advantage of the information on phase evolution as a function of gradient echo time in GEPCI echo train. PMID- 22305994 TI - Using Support Vector Machine to identify imaging biomarkers of neurological and psychiatric disease: a critical review. AB - Standard univariate analysis of neuroimaging data has revealed a host of neuroanatomical and functional differences between healthy individuals and patients suffering a wide range of neurological and psychiatric disorders. Significant only at group level however these findings have had limited clinical translation, and recent attention has turned toward alternative forms of analysis, including Support-Vector-Machine (SVM). A type of machine learning, SVM allows categorisation of an individual's previously unseen data into a predefined group using a classification algorithm, developed on a training data set. In recent years, SVM has been successfully applied in the context of disease diagnosis, transition prediction and treatment prognosis, using both structural and functional neuroimaging data. Here we provide a brief overview of the method and review those studies that applied it to the investigation of Alzheimer's disease, schizophrenia, major depression, bipolar disorder, presymptomatic Huntington's disease, Parkinson's disease and autistic spectrum disorder. We conclude by discussing the main theoretical and practical challenges associated with the implementation of this method into the clinic and possible future directions. PMID- 22305995 TI - The role of calcium in synaptic plasticity and motor learning in the cerebellar cortex. AB - The cerebellum is important for motor coordination, as well as motor learning and memories. Learning is believed to occur in the cerebellar cortex, in the form of synaptic plasticity. Central to motor learning theory are Purkinje cells (PCs), which are the sole output neurons of the cerebellar cortex. Motor memories are postulated to be stored in the form of long-term depression (LTD) at parallel fiber synapses with PCs, once thought to be the only plastic synapse in the cerebellar cortex. However, in the past few decades many studies have demonstrated that several other synapses in the cerebellar cortex are indeed plastic, and that LTD or long-term potentiation at these various synapses could affect the overall output signal of PCs from the cerebellar cortex. Almost all of these forms of synaptic plasticity are dependent on calcium to some extent. In the current review we discuss various types of synaptic plasticity in the cerebellar cortex and the role of calcium in these forms of plasticity. PMID- 22305996 TI - Intentional inhibition in human action: the power of 'no'. AB - The capacity to inhibit and withhold actions is a key feature of human cognition. Withholding action forms the basis of self-control, delayed gratification, social contracts, and trust in others. Most experimental studies of this function come from studying the processing of external stop signals. However, another important aspect of inhibition is 'will-power', i.e., intentional inhibitory control over one's own actions, in the absence of external countermanding signals. We review whether a concept of intentional inhibition is justified, and how it might differ from externally triggered inhibition. Further, we consider three types of neuroscientific evidence that can clarify the brain's mechanisms of inhibition: neuropsychology, neurostimulation and neuroimaging. Finally, we propose a model in which intentional inhibition, unlike externally triggered inhibition, is linked to representing longer range consequences of action decisions. We suggest that the human brain contains a 'neural brake' mechanism that blocks specific ongoing motor activity, and that this mechanism plays a key role in action decisions. PMID- 22305997 TI - Two numbers to assess hypertension control, simple? Maybe not. PMID- 22305998 TI - Aliskiren-based dual- and triple-combination therapies in high-risk US minority patients with stage 2 hypertension. AB - Previously, we reported the efficacy of aliskiren/amlodipine in US minority adults with stage 2 hypertension, with additional blood pressure (BP) lowering from the addition of hydrochlorothiazide (HCTZ). A subgroup analysis in patients with hypertension and comorbidities of diabetes, cardiometabolic syndrome, or obesity, and in black participants is reported. This 8-week, multicenter, double blind study included 412 self-identified minority patients with mean sitting systolic BP (msSBP) >=160 mm Hg and <200 mm Hg). Patients were randomized to receive either combination aliskiren/amlodipine 150/5 mg or amlodipine 5 mg. Doses were forced-titrated to a maximum of aliskiren/amlodipine/HCTZ 300/10/25 mg or aliskiren/amlodipine 300/10 mg, respectively. There were 256 black (62%), 118 diabetic (29%), 284 cardiometabolic syndrome (69%), and 249 obese (60%) randomized patients. Baseline msSBP was ~167 mm Hg across all subgroups. Least square mean reductions in msSBP, the primary efficacy outcome, from baseline to week 8 across all subgroups, ranged from 35 to 37 mm Hg with aliskiren/amlodipine/HCTZ and 28 to 30 mm Hg with aliskiren/amlodipine (P < .01 for all between-treatment comparisons). Both regimens were well tolerated. Among high-risk patients, such as diabetics or those with cardiometabolic syndrome, combination aliskiren/amlodipine is effective in lowering BP; the addition of HCTZ provided incremental BP-lowering efficacy while maintaining tolerability. However, because our subgroups were not mutually exclusive, the generalization of our findings to the population seen in clinical practice is limited. PMID- 22305999 TI - Mitochondrial electron transport and glycolysis are coupled in articular cartilage. AB - OBJECTIVE: Although the majority of the adenosine triphosphate (ATP) in chondrocytes is made by glycolysis rather than by oxidative phosphorylation in mitochondria there is evidence to suggest that reactive oxygen species produced by mitochondrial electron transport (ET) help to maintain cellular redox balance in favor of glycolysis. The objective of this study was to test this hypothesis by determining if rotenone, which inhibits ET and blocks oxidant production inhibits glycolytic ATP synthesis. DESIGN: Bovine osteochondral explants were treated with rotenone, an ET inhibitor; or oligomycin an ATP synthase inhibitor; or 2-fluoro-2-deoxy-D-glucose, a glycolysis inhibiter; or peroxide, an exogenous oxidant; or mitoquinone (MitoQ), a mitochondria-targeted anti-oxidant. Cartilage extracts were assayed for ATP, nicotine adenine dinucleotide (NAD+/H), and culture medium was assayed for pyruvate and lactate after 24 h of treatment. Imaging studies were used to measure superoxide production in cartilage. RESULTS: Rotenone and 2-FG caused a significant decline in cartilage ATP (P < 0.001). In contrast, ATP levels were not affected by oligomycin. Peroxide treatment blocked rotenone effects on ATP, while treatment with MitoQ significantly suppressed ATP levels. Rotenone and 2-FG caused a significant decline in pyruvate, but not in lactate production. NADH:NAD+ ratios decreased significantly in both rotenone and 2-FG-treated explants (P < 0.05). Rotenone also significantly reduced superoxide production. CONCLUSIONS: These findings showing a link between glycolysis and ET are consistent with previous reports on the critical need for oxidants to support normal chondrocyte metabolism. They suggest a novel role for mitochondria in cartilage homeostasis that is independent of oxidative phosphorylation. PMID- 22306000 TI - UTE-T2* mapping detects sub-clinical meniscus injury after anterior cruciate ligament tear. AB - OBJECTIVE: Meniscus tear is a known risk factor for osteoarthritis (OA). Quantitative assessment of meniscus degeneration, prior to surface break-down, is important to identification of early disease potentially amenable to therapeutic interventions. This work examines the diagnostic potential of ultrashort echo time-enhanced T2* (UTE-T2*) mapping to detect human meniscus degeneration in vitro and in vivo in subjects at risk of developing OA. DESIGN: UTE-T2* maps of 16 human cadaver menisci were compared to histological evaluations of meniscal structural integrity and clinical magnetic resonance imaging (MRI) assessment by a musculoskeletal radiologist. In vivo UTE-T2* maps were compared in 10 asymptomatic subjects and 25 ACL-injured patients with and without concomitant meniscal tear. RESULTS: In vitro, UTE-T2* values tended to be lower in histologically and clinically normal meniscus tissue and higher in torn or degenerate tissue. UTE-T2* map heterogeneity reflected collagen disorganization. In vivo, asymptomatic meniscus UTE-T2* values were repeatable within 9% (root mean-square average coefficient of variation). Posteromedial meniscus UTE-T2* values in ACL-injured subjects with clinically diagnosed medial meniscus tear (n=10) were 87% higher than asymptomatics (n=10, P<0.001). Posteromedial menisci UTE-T2* values of ACL-injured subjects without concomitant medial meniscal tear (n=15) were 33% higher than asymptomatics (P=0.001). Posterolateral menisci UTE T2* values also varied significantly with degree of joint pathology (P=0.001). CONCLUSION: Significant elevations of UTE-T2* values in the menisci of ACL injured subjects without clinical evidence of subsurface meniscal abnormality suggest that UTE-T2* mapping is sensitive to sub-clinical meniscus degeneration. Further study is needed to determine whether elevated subsurface meniscus UTE-T2* values predict progression of meniscal degeneration and development of OA. PMID- 22306001 TI - Enhanced anti-melanoma efficacy of interferon alfa-2b via inhibition of Shp2. AB - Interferon-alpha2b (IFN-alpha2b) is used to treat melanoma but there is a need to improve its efficacy. IFN-alpha2b signaling requires STAT1/STAT2 tyrosine phosphorylation and is subject to negative regulation by phosphatases. In this study, we determined whether inhibition of the protein tyrosine phosphatase Shp2 could enhance IFN-alpha2b responses in human melanoma cells. Shp2 knockdown increased IFN-alpha2b-stimulated STAT1 Tyr-701 phosphorylation and ISRE luciferase activity even though it did not affect STAT2 Tyr-690 phosphorylation in A375 cells. In A375 tumor xenografts, Shp2 knockdown enhanced the anti melanoma effect of IFN-alpha2b. Furthermore, the Shp2 inhibitor SPI-112Me increased the IFN-alpha2b-induced STAT1 activation and anti-proliferative response in A375 and SK-MEL-2 cells. These results demonstrate that inhibition of Shp2 can enhance the anti-melanoma activity of IFN-alpha2b. PMID- 22306002 TI - Generalized tonic-clonic seizure secondary to duloxetine poisoning: a short report with favorable out come. AB - Duloxetine is a potent and selective inhibitor of serotonin and norepinephrine reuptake (SNRI) with a weak activity over dopamine reuptake used in the treatment of major depressive disorder. Daily doses of 60 mg are effective in treatment of major depression. There are few cases of isolated duloxetine overdose in humans. We think this is the first report of a generalized tonic-clonic seizure following isolated duloxetine poisoning with a very high dosage. PMID- 22306003 TI - SUMO-2/3 conjugates accumulating under heat shock or MG132 treatment result largely from new protein synthesis. AB - Small ubiquitin-related modifiers 1, 2 and 3 (SUMO-1, -2, -3), members of the ubiquitin-like protein family, can be conjugated to various cellular proteins. Conjugates of SUMO-2 and SUMO-3 (SUMO-2/3) accumulate in cells exposed to various stress stimuli or to MG132 treatment. Although the proteins modified by SUMO-2/3 during heat shock or under MG132 treatment have been identified, the significance of this modification remains unclear. Our data show that the inhibition of translation by puromycin or cycloheximide blocks both the heat shock and MG132 induced accumulation of SUMO-2/3 conjugates in HEK 293T and U2OS cells. However, the heat shock induced accumulation of SUMO-2/3 conjugates was restored by proteasome inhibition, which suggests that the inhibition of translation did not abolish SUMOylation itself. Furthermore, we show that some of the proteins truncated due to the treatment by low concentration of puromycin are SUMOylated in HEK 293T cells. We suggest that the SUMO-2/3 conjugates accumulating under the heat shock or MG132 treatment result largely from new protein synthesis and that portion of them is incorrectly folded. PMID- 22306004 TI - Fluvoxamine increased glutamate release by activating both 5-HT(3) and sigma-1 receptors in prelimbic cortex of chronic restraint stress C57BL/6 mice. AB - Emerging evidence from therapeutic trials in humans and animal models suggests that in the treatment of depression, antidepressants play a role by targeting the glutamatergic system. Fluvoxamine is one of the widely used SSRIs which has been considered to target monoamine neurotransmitter reuptake mechanisms. However, whether fluvoxamine has an effect on the glutamate release is still unclear. The present experiment studied the effect of fluvoxamine on presynaptic glutamate release in prelimbic cortex, both in control C57BL/6 mice and chronic restraint stress C57BL/6 mice, and further investigated the mechanism underlying this effect by using patch clamp, on-line fluorimetry, pharmacological approaches combined with other techniques. The results showed that fluvoxamine increased the glutamate release in the depression model mice but it had no effect on the glutamate release in the control mice. The mechanism underlying these effects in depression model mice was that, fluvoxamine firstly activated presynaptic 5-HT(3) receptors, which transiently increased the Ca(2+) concentration. The increase of Ca(2+) concentration via 5-HT(3) receptors caused the activation of sigma-1 receptors, which were activated by fluvoxamine. The activation of sigma-1 receptors increased the intrasynaptosomal Ca(2+) concentration significantly through the outflow of endoplasmic reticulum calcium and finally activated PKC. These results suggested that fluvoxamine may have a selective effect and different mechanism based on the condition of animal. PMID- 22306005 TI - Hepcidin and iron homeostasis. AB - Despite fluctuations in dietary iron intake and intermittent losses through bleeding, the plasma iron concentrations in humans remain stable at 10-30 MUM. While most of the iron entering blood plasma comes from recycling, appropriate amount of iron is absorbed from the diet to compensate for losses and maintain nontoxic amounts in stores. Plasma iron concentration and iron distribution are similarly regulated in laboratory rodents. The hepatic peptide hepcidin was identified as the systemic iron-regulatory hormone. In the efferent arc, hepcidin regulates intestinal iron absorption, plasma iron concentrations, and tissue iron distribution by inducing degradation of its receptor, the cellular iron exporter ferroportin. Ferroportin exports iron into plasma from absorptive enterocytes, from macrophages that recycle the iron of senescent erythrocytes, and from hepatocytes that store iron. In the more complex and less well understood afferent arc, hepatic hepcidin synthesis is transcriptionally regulated by extracellular and intracellular iron concentrations through a molecular complex of bone morphogenetic protein receptors and their iron-specific ligands, modulators and iron sensors. Through as yet undefined pathways, hepcidin is also homeostatically regulated by the iron requirements of erythroid precursors for hemoglobin synthesis. In accordance with the role of hepcidin-mediated iron redistribution in host defense, hepcidin production is regulated by inflammation as well. Increased hepcidin concentrations in plasma are pathogenic in iron restrictive anemias including anemias associated with inflammation, chronic kidney disease and some cancers. Hepcidin deficiency causes iron overload in hereditary hemochromatosis and ineffective erythropoiesis. Hepcidin, ferroportin and their regulators represent potential targets for the diagnosis and treatment of iron disorders and anemias. This article is part of a Special Issue entitled: Cell Biology of Metals. PMID- 22306006 TI - Role of metal in folding and stability of copper proteins in vitro. AB - Metal coordination is required for function of many proteins. For biosynthesis of proteins coordinating a metal, the question arises if the metal binds before, during or after folding of the polypeptide. Moreover, when the metal is bound to the protein, how does its coordination affect biophysical properties such as stability and dynamics? Understanding how metals are utilized by proteins in cells on a molecular level requires accurate descriptions of the thermodynamic and kinetic parameters involved in protein-metal complexes. Copper is one of the essential transition metals found in the active sites of many key proteins. To avoid toxicity of free copper ions, living systems have developed elaborate copper-transport systems that involve dedicated proteins that facilitate efficient and specific delivery of copper to target proteins. This review describes in vitro and in silico biophysical work assessing the role of copper in folding and stability of copper-binding proteins. Examples of proteins discussed are: a blue-copper protein (Pseudomonas aeruginosa azurin), members of copper transport systems (bacterial CopZ, human Atox1 and ATP7B domains) and multi copper ferroxidases (yeast Fet3p and human ceruloplasmin). The consequences of interactions between copper proteins and platinum-complexes are also discussed. This article is part of a Special Issue entitled: Cell Biology of Metals. PMID- 22306007 TI - E-mail invitations to general practitioners were as effective as postal invitations and were more efficient. AB - OBJECTIVE: To evaluate which of two invitation methods, e-mail or post, was most effective at recruiting general practitioners (GPs) to an online trial. STUDY DESIGN AND SETTING: Randomized controlled trial. Participants were GPs in Scotland, United Kingdom. RESULTS: Two hundred and seventy GPs were recruited. Using e-mail did not improve recruitment (risk difference=0.7% [95% confidence interval -2.7% to 4.1%]). E-mail was, however, simpler to use and cheaper, costing L3.20 per recruit compared with L15.69 for postal invitations. Reminders increased recruitment by around 4% for each reminder sent for both invitation methods. CONCLUSIONS: In the Scottish context, inviting GPs to take part in an online trial by e-mail does not adversely affect recruitment and is logistically easier and cheaper than using postal invitations. PMID- 22306008 TI - Expression of human ABCB5 confers resistance to taxanes and anthracyclines. AB - Human ABCB5, an ATP-binding cassette (ABC) transporter gene, has two major mRNA species. One transcript encodes an 812 amino acid polypeptide, ABCB5beta, with a transmembrane domain and a nucleotide-binding domain. We isolated the cDNA of another ABCB5 mRNA that encodes a 1257 amino acid polypeptide. The translated ABCB5 protein is a full-sized ABC transporter that has an internally duplicated structure with two transmembrane domains and two nucleotide-binding domains. The 5' and 3' parts of the ABCB5 mRNA were expressed in the prostate and testis. HEK293 cells transfected with the ABCB5 cDNA expressed a 150-160kDa protein. The ABCB5 transfectants showed approximately 1.5-fold higher resistance to doxorubicin, and 2- to 3-fold higher resistance to paclitaxel and docetaxel. Cellular uptake of radiolabeled paclitaxel and docetaxel in the transfectants was lower than that in the parental HEK293 cells. Treatment of the transfectants with ABCB5-targeted siRNA lowered their resistance to docetaxel. Revertant cells that express a reduced amount of ABCB5 also showed a lowered level of docetaxel resistance. These results indicated that the expression of ABCB5 conferred resistance to taxanes and anthracyclines. Membrane vesicles prepared from ABCB5 baculovirus-infected Sf21 cells showed higher vanadate-sensitive ATPase activity than the Sf21 control vesicles. The k(m) and V(max) values of ATPase activity in the ABCB5 vesicles were 1.8mM and 65nmol/min/mg protein, respectively. ABCB5 ATPase activity was 1.25-fold higher in the presence of 100MUM docetaxel than it was in the absence of docetaxel. These results indicates that the full-length ABCB5 protein has ATPase activity that is sensitive to docetaxel. PMID- 22306009 TI - Biophysical characterisation of the nucleocapsid protein from a highly pathogenic porcine reproductive and respiratory syndrome virus strain. AB - The arterivirus nucleocapsid (N) protein is a multifunctional protein that binds viral RNA for encapsidation and has potential roles in host cell processes. This study characterised the N protein from a highly virulent North American strain of porcine reproductive and respiratory syndrome virus (PRRSV). The association with viral RNA was mapped to defined motifs on the N protein. The results indicated that disulphide bridge formation played a key role in RNA binding, offering an explanation why infectious virus cannot be rescued if cysteine residues are mutated, and that multiple sites may promote RNA binding. PMID- 22306010 TI - Chromatin plasticity as a differentiation index during muscle differentiation of C2C12 myoblasts. AB - Skeletal muscle undergoes complicated differentiation steps that include cell cycle arrest, cell fusion, and maturation, which are controlled through sequential expression of transcription factors. During muscle differentiation, remodeling of the epigenetic landscape is also known to take place on a large scale, determining cell fate. In an attempt to determine the extent of epigenetic remodeling during muscle differentiation, we characterized the plasticity of the chromatin structure using C2C12 myoblasts. Differentiation of C2C12 cells was induced by lowering the serum concentration after they had reached full confluence, resulting in the formation of multi-nucleated myotubes. Upon induction of differentiation, the nucleus size decreased whereas the aspect ratio increased, indicating the presence of force on the nucleus during differentiation. Movement of the nucleus was also suppressed when differentiation was induced, indicating that the plasticity of chromatin changed upon differentiation. To evaluate the histone dynamics during differentiation, FRAP experiment was performed, which showed an increase in the immobile fraction of histone proteins when differentiation was induced. To further evaluate the change in the histone dynamics during differentiation, FCS was performed, which showed a decrease in histone mobility on differentiation. We here show that the plasticity of chromatin decreases upon differentiation, which takes place in a stepwise manner, and that it can be used as an index for the differentiation stage during myogenesis using the state diagram developed with the parameters obtained in this study. PMID- 22306011 TI - p-Synephrine stimulates glucose consumption via AMPK in L6 skeletal muscle cells. AB - Interest in p-synephrine, the primary protoalkaloid in the extract of bitter orange and other citrus species, has increased due to its various pharmacological effects and related adverse effects. The lipolytic activity of p-synephrine has been repeatedly revealed by in vitro and in vivo studies and p-synephrine is currently marketed as a dietary supplement for weight loss. The present study investigated the effect of p-synephrine on glucose consumption and its action mechanism in L6 skeletal muscle cells. Treatment of L6 skeletal muscle cells with p-synephrine (0-100MUM) did not affect cell viability and increased basal glucose consumption up to 50% over the control in a dose-dependent manner. The basal- or insulin-stimulated lactic acid production as well as glucose consumption was significantly increased by the addition of p-synephrine. p-Synephrine stimulated the phosphorylation of AMPK but not of Akt. p-Synephrine-induced glucose consumption was sensitive to the inhibition of AMPK but not to the inhibition of PI3 kinase. p-Synephrine also stimulated the translocation of Glut4 from the cytoplasm to the plasma membrane; this stimulation was suppressed by the inhibition of AMPK, but not of PI3 kinase. Taken together, p-synephrine can stimulate glucose consumption (Glut4-dependent glucose uptake) by stimulating AMPK activity, regardless of insulin-stimulated PI3 kinase-Akt activity in L6 skeletal muscle cells. PMID- 22306012 TI - Chemically dimerized intravenous immunoglobulin has potent ameliorating activity in a mouse immune thrombocytopenic purpura model. AB - High-dose intravenous immunoglobulin (IVIG) preparations are currently used for the treatment of autoimmune diseases such as immune thrombocytopenic purpura (ITP). Although the mechanisms of IVIG efficacy remain enigmatic, some clinical and laboratory studies suggest that interaction of the Fc domain of IgG, especially the Fc domain of dimeric IgG, with its receptors (Fc gamma receptors; FcgammaRs) plays an essential role. In this study, IVIG was dimerized with chemical crosslinkers to augment its therapeutic efficacy. Dimerized IVIG was found to have a much higher affinity for FcgammaRs than monomeric IVIG. In a mouse ITP model, chemically dimerized IVIG abrogated the decrease in platelet numbers in the blood that was caused by an anti-platelet antibody at a dose that was one tenth of the required dose of IVIG. These results suggest that chemical dimerization of IVIG should greatly improve the efficacy of IVIG therapy of ITP. PMID- 22306013 TI - SVM-T-RFE: a novel gene selection algorithm for identifying metastasis-related genes in colorectal cancer using gene expression profiles. AB - Although metastasis is the principal cause of death cause for colorectal cancer (CRC) patients, the molecular mechanisms underlying CRC metastasis are still not fully understood. In an attempt to identify metastasis-related genes in CRC, we obtained gene expression profiles of 55 early stage primary CRCs, 56 late stage primary CRCs, and 34 metastatic CRCs from the expression project in Oncology (http://www.intgen.org/expo/). We developed a novel gene selection algorithm (SVM T-RFE), which extends support vector machine recursive feature elimination (SVM RFE) algorithm by incorporating T-statistic. We achieved highest classification accuracy (100%) with smaller gene subsets (10 and 6, respectively), when classifying between early and late stage primary CRCs, as well as between metastatic CRCs and late stage primary CRCs. We also compared the performance of SVM-T-RFE and SVM-RFE gene selection algorithms on another large-scale CRC dataset and the five public microarray datasets. SVM-T-RFE bestowed SVM-RFE algorithm in identifying more differentially expressed genes, and achieving highest prediction accuracy using equal or smaller number of selected genes. A fraction of selected genes have been reported to be associated with CRC development or metastasis. PMID- 22306014 TI - pp-GalNAc-T13 induces high metastatic potential of murine Lewis lung cancer by generating trimeric Tn antigen. AB - In order to analyze the mechanisms for cancer metastasis, high metastatic sublines (H7-A, H7-Lu, H7-O, C4-sc, and C4-ly) were obtained by repeated injection of mouse Lewis lung cancer sublines H7 and C4 into C57BL/6 mice. These sublines exhibited increased proliferation and invasion activity in vitro. Ganglioside profiles exhibited lower expression of GM1 in high metastatic sublines than the parent lines. Then, we established GM1-Si-1 and GM1-Si-2 by stable silencing of GM1 synthase in H7 cells. These GM1-knockdown clones exhibited increased proliferation and invasion. Then, we explored genes that markedly altered in the expression levels by DNA microarray in the combination of C4 vs. C4-ly or H7 vs. H7 (GM1-Si). Consequently, pp-GalNAc-T13 gene was identified as up-regulated genes in the high metastatic sublines. Stable transfection of pp-GalNAc-T13 cDNA into C4 (T13-TF) resulted in increased invasion and motility. Then, immunoblotting and flow cytometry using various antibodies and lectins were performed. Only anti-trimeric Tn antibody (mAb MLS128), showed increased expression levels of trimeric Tn antigen in T13-TF clones. Moreover, immunoprecipitation/immunoblotting was performed by mAb MLS128, leading to the identification of an 80 kDa band carrying trimeric Tn antigen, i.e. Syndecan-1. Stable silencing of endogenous pp-GalNAc-T13 in C4-sc (T13-KD) revealed that primary tumors generated by subcutaneous injection of T13-KD clones showed lower coalescence to fascia and peritoneum, and significantly reduced lung metastasis than control clones. These data suggested that high expression of pp GalNAc-T13 gene generated trimeric Tn antigen on Syndecan-1, leading to the enhanced metastasis. PMID- 22306015 TI - Confirmation of TBK1 duplication in normal tension glaucoma. PMID- 22306016 TI - Dose-dependent treatment of optic nerve crush by exogenous systemic mutant erythropoietin. AB - The goal of the present study was to determine the minimum concentration of systemic erythropoietin-R76E required for neuroprotection in the retina. Erythropoietin (EPO) exhibits neuroprotective effects in both in vitro and in vivo models of neuronal cell death although its classical function is the regulation of red blood cell production. It can cross the blood brain barrier and therefore can be delivered systemically to affect the retina. However, long-term treatment with exogenous erythropoietin causes polycythemia. To decrease this potentially lethal effect, we generated and tested a modified form that contains a single arginine to glutamate mutation at the 76th position (EPO-R76E). In previous studies, this mutant protected retinal neurons in mouse models of retinal degeneration and glaucoma with similar efficacy as wild-type EPO. However, EPO-R76E has attenuated erythropoietic activity, therefore, neuroprotection can be achieved without causing a significant rise in hematocrit. BALB/cByJ mice received a single intramuscular injection of recombinant adeno associated virus carrying enhanced green fluorescent protein, Epo, or Epo-R76E. To result in continuous production of four different doses of EPO-R76E, two doses of two different serotypes (2/5 and 2/8) were used. Mice were subjected to optic nerve crush and analysis was performed thirty days later. EPO-R76E showed dose dependent protection of the retinal ganglion cell bodies, but was unable to prevent axonal degeneration. Furthermore, EPO-R76E induced a dose-dependent rise in the hematocrit that was still attenuated as compared to wild-type EPO. PMID- 22306017 TI - Interleukin 23 production by intestinal CD103(+)CD11b(+) dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense. AB - Microbial penetration of the intestinal epithelial barrier triggers inflammatory responses that include induction of the bactericidal C-type lectin RegIIIgamma. Systemic administration of flagellin, a bacterial protein that stimulates Toll like receptor 5 (TLR5), induces epithelial expression of RegIIIgamma and protects mice from intestinal colonization with antibiotic-resistant bacteria. Flagellin induced RegIIIgamma expression is IL-22 dependent, but how TLR signaling leads to IL-22 expression is incompletely defined. By using conditional depletion of lamina propria dendritic cell (LPDC) subsets, we demonstrated that CD103(+)CD11b(+) LPDCs, but not monocyte-derived CD103(-)CD11b(+) LPDCs, expressed high amounts of IL-23 after bacterial flagellin administration and drove IL-22-dependent RegIIIgamma production. Maximal expression of IL-23 subunits IL-23p19 and IL-12p40 occurred within 60 min of exposure to flagellin. IL-23 subsequently induced a burst of IL-22 followed by sustained RegIIIgamma expression. Thus, CD103(+)CD11b(+) LPDCs, in addition to promoting long-term tolerance to ingested antigens, also rapidly produce IL-23 in response to detection of flagellin in the lamina propria. PMID- 22306018 TI - Intracellular calcium chelation with BAPTA-AM modulates ethanol-induced behavioral effects in mice. AB - Calcium (Ca(2+)) has been characterized as one of the most ubiquitous, universal and versatile intracellular signaling molecules responsible for controlling numerous cellular processes. Ethanol-induced effects on Ca(2+) distribution and flux have been widely studied in vitro, showing that acute ethanol administration can modulate intracellular Ca(2+) concentrations in a dose dependent manner. In vivo, the relationship between Ca(2+) manipulation and the corresponding ethanol induced behavioral effects have focused on Ca(2+) flux through voltage-gated Ca(2+) channels. The present study investigated the role of inward Ca(2+) currents in ethanol-induced psychomotor effects (stimulation and sedation) and ethanol intake. We studied the effects of the fast Ca(2+) chelator, BAPTA-AM, on ethanol-induced locomotor activity and the sedative effects of ethanol. Swiss (RjOrl) mice were pretreated with BAPTA-AM (0-10 mg/kg) 30 min before an ethanol (0-4 g/kg) challenge. Our results revealed that pretreatment with BAPTA-AM prevented locomotor stimulation produced by ethanol without altering basal locomotion. In contrast, BAPTA-AM reversed ethanol-induced hypnotic effects. In a second set of experiments, we investigated the effects of intracellular Ca(2+) chelation on ethanol intake. Following a drinking-in-the-dark methodology, male C57BL/6J mice were offered 20% v/v ethanol, tap water, or 0.1% sweetened water. The results of these experiments revealed that BAPTA-AM pretreatment (0-5 mg/kg) reduced ethanol consumption in a dose-dependent manner while leaving water and sweetened water intake unaffected. Our findings support the role of inward Ca(2+) currents in mediating different behavioral responses induced by ethanol. Our results are discussed together with data indicating that ethanol appears to be more sensitive to intracellular Ca(2+) manipulations than other psychoactive drugs. PMID- 22306019 TI - Treatment strategies for patients with stage IV rectal cancer: a report from the Swedish Rectal Cancer Registry. AB - BACKGROUND: The optimal treatment strategy for patients with stage IV rectal cancer is unclear. The aim of the present study was to describe trends and compare the different treatment strategies for this group of patients at a national level and over time. METHODS: Data from 2758 rectal cancer patients with (stage IV) and 13,420 without metastases (stage I-III) were available from the Swedish Rectal Cancer Registry between January 1995 and December 2006. RESULTS: Patients with stage IV disease increased from 15% to 19% between 1995 and 2006 (p<0.001) and the frequency of patients not operated on increased from 13% to 26% (p<0.001). Postoperative 30 day mortality after bowel resection was 2% and after exploratory laparotomy 9%. Median survival for stage IV patients after bowel resection was 16.3 months, exploratory laparotomy 6.1 months and for patients having no surgery 4.6 months. Over time survival was improved for patients aged 60-69 years, irrespective of the treatment given. An increased risk of death was associated with: age >80 years, operation at a local hospital, treatment in earlier time periods, not receiving preoperative radio- or chemotherapy and not having a bowel resection. CONCLUSIONS: In the latest time period survival was improved for rectal cancer patients in stage IV despite the great increase in non operated patients. Patients aged >80 years should be carefully assessed and staged before surgery. The survival advantage for stage IV rectal cancer patients who underwent primary tumour resection is probably due to selection to more favourable cases. PMID- 22306020 TI - Theranostic liposomes of TPGS coating for targeted co-delivery of docetaxel and quantum dots. AB - The aim of this work was to develop a new type of D-alpha-tocopheryl polyethylene glycol 1000 succinate mono-ester (TPGS) coated multi-functional (theranostic) liposomes, which contain both docetaxel and quantum dots (QDs) for cancer imaging and therapy. Non-targeting and folate receptor targeting TPGS coated theranostic liposomes were prepared by the solvent injection method and characterized for their particle size, polydispersity, zeta potential, surface chemistry and drug encapsulation efficiency. MCF-7 breast cancer cells of folate receptor overexpression were employed as an in vitro model to assess cellular uptake and cytotoxicity of the drug and QDs loaded liposomes. The mean particle size of the non-targeting and the targeting liposomes was found to be 202 and 210 nm, respectively. High resolution field emission transmission electron microscopy (FETEM) confirmed the presence of quantum dots in the peripheral hydrophobic membranes of the liposomes. The qualitative internalization of multi-functional liposomes by MCF-7 cells was visualized by confocal laser scanning microscopy (CLSM). The IC50 value, which is the drug concentration needed to kill 50% cells in a designated time period, was found to be 9.54 +/- 0.76, 1.56 +/- 0.19 and 0.23 +/- 0.05 MUg/ml for the commercial Taxotere((r)), non-targeting and targeting liposomes, respectively after 24 h culture with MCF-7 cells. The targeting multi-functional liposomes showed greater efficacy than the non targeting liposomes and thus great potential to improve the cancer imaging and therapy. PMID- 22306021 TI - The effect of injectable gelatin-hydroxyphenylpropionic acid hydrogel matrices on the proliferation, migration, differentiation and oxidative stress resistance of adult neural stem cells. AB - Transplanted or endogenous neural stem cells often lack appropriate matrix in cavitary lesions in the central nervous system. In this study, gelatin hydroxyphenylpropionic acid (Gtn-HPA), which could be enzymatically crosslinked with independent tuning of crosslinking degree and gelation rate, was explored as an injectable hydrogel for adult neural stem cells (aNSCs). The storage modulus of Gtn-HPA could be tuned (449-1717 Pa) to approximate adult brain tissue. Gtn HPA was cytocompatible with aNSCs (yielding high viability >93%) and promoted aNSC adhesion. Gtn-HPA demonstrated a crosslinking-based approach for preconditioning aNSCs and increased the resistance of aNSCs to oxidative stress, improving their viability from 8-15% to 84% when challenged with 500 MUM H(2)O(2). In addition, Gtn-HPA was able to modulate proliferation and migration of aNSCs in relation to the crosslinking degree. Finally, Gtn-HPA exhibited bias for neuronal cells. In mixed differentiation conditions, Gtn-HPA increased the proportion of aNSCs expressing neuronal marker beta-tubulin III to a greater extent than that for astrocytic marker glial fibrillary acidic protein, indicating an enhancement in differentiation towards neuronal lineage. Between neuronal and astrocytic differentiation conditions, Gtn-HPA also selected for higher survival in the former. Overall, Gtn-HPA hydrogels are promising injectable matrices for supporting and influencing aNSCs in ways that may be beneficial for brain tissue regeneration after injuries. PMID- 22306022 TI - Adult stem cell-based tissue engineered blood vessels: a review. AB - With the high occurrence of cardiovascular disease and increasing numbers of patients requiring vascular access, there is a significant need for a small diameter (<6 mm inner diameter) vascular graft that can provide long-term patency. Tissue engineering provides a very promising solution to this need. Approaches utilizing adult stem cells can address limitations previously realized in the use of terminally differentiated vascular cells, without introducing the ethical concerns that continue to limit the exploration and use of embryonic stem cells. This review summarizes the exciting work that has been reported on the application of adult stem cells to tissue engineered vascular grafts. Work in this area to date has employed bone marrow mononuclear progenitor cells, mesenchymal stem cells from various sources, and endothelial precursor cells. PMID- 22306023 TI - Financial burden of drug expenditures in Poland. AB - OBJECTIVES: This paper investigates the level of catastrophic out-of-pocket pharmaceutical (OOP) expenditures and their impoverishment effect in Poland. METHODS: We use data from a representative sample of Polish households covering 2000, 2003, 2005, 2007 and 2009. We estimate the incidence and intensity of catastrophic drug expenditure and its impoverishment effects using the methods introduced by Wagstaff and van Doorslaer. We obtain estimates for the full population and for the subsample of retired and chronically ill. RESULTS: The incidence and intensity of catastrophic drug expenditures increased over the years and they are concentrated among the poor. The proportion of households that spent at least 10% of their income on pharmaceuticals reached 18% in 2009. This figure is higher than the evidence found in other countries for total health expenditure. Pharmaceutical expenditures increased poverty rates, and the evidence suggests that the poverty impact of OOP expenditures in the last decade was mainly driven by poor people becoming poorer. The effects are more conspicuous among the retired and chronically ill. CONCLUSIONS: Our findings indicate that OOP pharmaceutical expenditures in Poland are a severe financial burden and that policies aimed at both lowering the price of effective drugs and decreasing consumption of the ineffective ones are needed. PMID- 22306024 TI - Responding to diversity: an exploratory study of migrant health policies in Europe. AB - There has been growing international attention to migrant health, reflecting recognition of the need for health systems to adapt to increasingly diverse populations. However, reports from health policy experts in 25 European countries suggest that by 2009 only eleven countries had established national policies to improve migrant health that go beyond migrants' statutory or legal entitlement to care. The objective of this paper is to compare and contrast the content of these policies and analyse their strengths and limitations. The analysis suggests that most of the national policies target either migrants or more established ethnic minorities. Countries should address the diverse needs of both groups and could learn from "intercultural" health care policies in Ireland and, in the past, the Netherlands. Policies in several countries prioritise specific diseases or conditions, but these differ and it is not clear whether they accurately reflect real differences in need among countries. Policy initiatives typically involve training health workers, providing interpreter services and/or 'cultural mediators', adapting organizational culture, improving data collection and providing information to migrants on health problems and services. A few countries stand out for their quest to increase migrants' health literacy and their participation in the development and implementation of policy. Progressive migrant health policies are not always sustainable as they can be undermined or even reversed when political contexts change. The analysis of migrant health policies in Europe is still in its infancy and there is an urgent need to monitor the implementation and evaluate the effectiveness of these diverse policies. PMID- 22306025 TI - Treatment and prevention of natural heartworm (Dirofilaria immitis) infections in red pandas (Ailurus fulgens) with selamectin and ivermectin. AB - Ten of the 48 red pandas in the Chengdu Research Base of Giant Panda Breeding, Sichuan province, China, died in 2006 after prolonged periods of depression, weight loss, and mucocutaneous membrane xanthochromia. During postmortem examination, live heartworms were found in the right cardiac ventricles and pulmonary arteries of all 10 animals. Selamectin and ivermectin were used for clinical prophylaxis in the remaining red pandas between December 2006 and November 2010. We observed a gradual decrease in morbidity and mortality during this period. As a consequence of our prophylaxis program, dirofilariosis did not occur in the remaining red pandas at Chengdu Research Base during 2010. PMID- 22306026 TI - Modeling of a violaxanthin-chlorophyll b chromophore pair in its LHCII environment using CAM-B3LYP. AB - Collecting energy for photosystem II is facilitated by several pigments, xanthophylls and chlorophylls, embedded in the light harvesting complex II (LHCII). One xanthophyll, violaxanthin (Vio), is loosely bound at a site close to a chlorophyll b (Chl). No final answer has yet been found for the role of this specific xanthophyll. We study the electronic structure of Vio in the presence of Chl and under the influence of the LHCII environment, represented by a point charge field (PCF). We compare the capability of the long range corrected density functional theory (DFT) functional CAM-B3LYP to B3LYP for the modeling of the UV/vis spectrum of the Vio+Chl pair. CAM-B3LYP was reported to allow for a very realistic reproduction of bond length alternation of linear polyenes, which has considerable impact on the carotenoid structure and spectrum. To account for the influence of the LHCII environment, the chromophore geometries are optimized using an ONIOM(DFT/6-31G(d):PM6) scheme. Our calculations show that the energies of the locally excited states are almost unaffected by the presence of the partner chromophore or the PCF. There are, however, indications for excitonic coupling of the Chl Soret band and Vio. We propose that Vio may accept energy from blue-light excited Chl. PMID- 22306027 TI - Liver-directed therapies: does it make sense in the current therapeutic strategy for patients with confined liver colorectal metastases? AB - Nearly half of patients with colorectal cancer will have metastases in the course of their disease and the liver appears to be the most common location for metastases. For patients with confined hepatic colorectal metastases, complete surgical resection is the only chance for cure, with a 5-year postoperative survival rate between 35% and 50%. Over the past 5 years, combinations of chemotherapy with targeted therapies have succeeded in inducing tumoral response and have made curative surgery of initially unresectable liver metastases possible. However despite optimal preoperative treatment, disease in the majority of patients remains unresectable. For patients with liver-limited or liver dominant metastatic colorectal cancer (mCRC), the current challenges are to explore different locoregional treatments to improve local control, overall survival (OS), and curative resection. In this way, liver-directed therapy, which is defined by injection, infusion, or embolization of chemotherapy or loaded radionuclide (with radioactive yttrium-90) microspheres into the arterial liver vasculature, has been an appealing investigational method for patients with liver confined mCRC, in whom it has yielded reproducibly higher response rates (RRs) than conventional intravenous therapy. In this article, we propose to review, compare, and discuss the clinical benefit, the current indications, and the optimal use of liver-directed therapies for patients with liver-dominant mCRC. PMID- 22306028 TI - Inhibition of NEDD8-conjugation pathway by novel molecules: potential approaches to anticancer therapy. AB - Cancer cells can survive through the upregulation of cell cycle and the escape from apoptosis induced by numerous cellular stresses. In the normal cells, these biological cascades depend on scheduled proteolytic degradation of regulatory proteins via the ubiquitin-proteasome pathway. Therefore, interruption of regulated proteolytic pathways leads to abnormal cell-proliferation. Ubiquitin ligases called SCF complex (consisting of Skp-1, cullin, and F-box protein) or CRL (cullin-RING ubiquitin ligase) are predominant in a family of E3 ubiquitin ligases that control a final step in ubiquitination of diverse substrates. To a great extent, the ubiquitin ligase activity of the SCF complex requires the conjugation of NEDD8 to cullins, i.e. scaffold proteins. This review is anticipated to review the downregulation system of NEDD8 conjugation by several factors including a chemical compound such as MLN4924 and protein molecules (e.g. COP9 signalosome, inactive mutant of Ubc12, and NUB1/NUB1L). Since the downregulation of NEDD8 conjugation affects cell-cycle progression by inhibiting the ligase activity of SCF complexes, such knowledge in the NEDD8-conjugation pathway will contribute to the more magnificent therapies that selectively suppress tumorigenesis. PMID- 22306029 TI - Molecular mechanisms underlying chemical liver injury. AB - The liver is necessary for survival. Its strategic localisation, blood flow and prominent role in the metabolism of xenobiotics render this organ particularly susceptible to injury by chemicals to which we are ubiquitously exposed. The pathogenesis of most chemical-induced liver injuries is initiated by the metabolic conversion of chemicals into reactive intermediate species, such as electrophilic compounds or free radicals, which can potentially alter the structure and function of cellular macromolecules. Many reactive intermediate species can produce oxidative stress, which can be equally detrimental to the cell. When protective defences are overwhelmed by excess toxicant insult, the effects of reactive intermediate species lead to deregulation of cell signalling pathways and dysfunction of biomolecules, leading to failure of target organelles and eventual cell death. A myriad of genetic factors determine the susceptibility of specific individuals to chemical-induced liver injury. Environmental factors, lifestyle choices and pre-existing pathological conditions also have roles in the pathogenesis of chemical liver injury. Research aimed at elucidating the molecular mechanism of the pathogenesis of chemical-induced liver diseases is fundamental for preventing or devising new modalities of treatment for liver injury by chemicals. PMID- 22306030 TI - Amylin-leptin coadministration stimulates central histaminergic signaling in rats. AB - Combined amylin+leptin (AMN+LEP) can reduce diet induced obesity and is very effective in combating LEP resistance. The purpose of this study was to evaluate the effect of AMN+LEP on central histaminergic signaling in lean and obese rats. Male rats were administered LEP (300 MUg/kg/d), AMN (100 MUg/kg/d), AMN+LEP or vehicle (SAL, 0.9% normal saline), via a subcutaneous mini-osmotic pump or single injection (LEP, 300 MUg/kg and AMN, 100 MUg/kg) for acute studies. AMN+LEP administration increased expression of histamine H1 receptor (HIR) and histidine decarboxylase (HDC) mRNA in the hypothalamus. Increased levels of H1R were seen in arcuate (Arc) and ventromedial hypothalamus (VMH) as well as the area postrema (APOS) and nucleus of solitary tract (NTS) following AMN+LEP administration. APOS and NTS also showed expression of immediate early gene c-FOS in the hindbrain in AMN+LEP-treated rats. We confirmed previous evidence indicating that AMN+LEP increased STAT-3 protein phosphorylation in Arc and VMH. Finally, by in vivo microdialysis, we observed an increase in methyl HIS levels in the VMH of AMN, LEP and AMN+LEP-treated rats. Taken together, these observations are consistent with an important role that neuronal HIS may play in mediating the potent effects of AMN+LEP on food intake and body weight. PMID- 22306031 TI - Motor neuron pathology and behavioral alterations at late stages in a SMA mouse model. AB - Spinal muscular atrophy (SMA) is a neurogenetic autosomal recessive disorder characterized by degeneration of lower motor neurons. The validation of appropriate animal models is key in fostering SMA research. Recent studies set up an animal model showing long survival and slow disease progression. This model is knocked out for mouse SMN (Smn(-/-)) gene and carries a human mutation of the SMN1 gene (SMN1A2G), along with human SMN2 gene. In the present study we used this knock out double transgenic mouse model (SMN2(+/+); Smn(-/-); SMN1A2G(+/-)) to characterize the spinal cord pathology along with motor deficit at prolonged survival times. In particular, motor neuron loss was established stereologically (44.77%) after motor deficit reached a steady state. At this stage, spared motor neurons showed significant cell body enlargement. Moreover, similar to what was described in patients affected by SMA we found neuronal heterotopy (almost 4% of total motor neurons) in the anterior white matter. The delayed disease progression was likely to maintain fair motor activity despite a dramatic loss of large motor neurons. This provides a wonderful tool to probe novel drugs finely tuning the survival of motor neurons. In fact, small therapeutic effects protracted over considerable time intervals (even more than a year) are expected to be magnified. PMID- 22306032 TI - Rhodopsin expression in the zebrafish pineal gland from larval to adult stage. AB - The zebrafish pineal gland plays an important role in different physiological functions including the regulation of the circadian clock. In the fish pineal gland the pinealocytes are made up of different segments: outer segment, inner segment and basal pole. Particularly, in the outer segment the rhodopsin participates in the external environment light reception that represents the first biochemical step in the melatonin production. It is well known that the rhodopsin in the adult zebrafish is well expressed in the pineal gland but both the expression and the cellular localization of this protein during development remain still unclear. In this study using qRT-PCR, sequencing and immunohistochemistry the expression as well as the protein localization of the rhodopsin in the zebrafish from larval (10 dpf) to adult stage (90 dpf) were demonstrated. The rhodopsin mRNA expression presents a peak of expression at 10 dpf, a further reduction to 50 dpf before increasing again in the adult stage. Moreover, the cellular localization of the rhodopsin-like protein was always localized in the pinealocyte at all ages examined. Our results demonstrated the involvement of the rhodopsin in the zebrafish pineal gland physiology particularly in the light capture during the zebrafish lifespan. PMID- 22306033 TI - Nucleus ambiguus cholinergic neurons activated by acupuncture: relation to enkephalin. AB - Acupuncture regulates autonomic function. Our previous studies have shown that electroacupuncture (EA) at the Jianshi-Neiguan acupoints (P5-P6, underlying the median nerve) inhibits central sympathetic outflow and attenuates excitatory cardiovascular reflexes, in part, through an opioid mechanism. It is unknown if EA at these acupoints influences the parasympathetic system. Thus, using c-Fos expression, we examined activation of nucleus ambiguus (NAmb) neurons by EA, their relation to cholinergic (preganglionic parasympathetic) neurons and those containing enkephalin. To enhance detection of cell bodies containing enkephalin, colchicine (90-100 MUg/kg) was administered into the subarachnoid space of cats 30 h prior to EA or sham-operated controls for EA. Following bilateral barodenervation and cervical vagotomy, either EA for 30 min at P5-P6 acupoints or control stimulation (needle placement at P5-P6 without stimulation) was applied. While perikarya containing enkephalin were observed in some medullary nuclei (e.g., raphe), only enkephalin-containing neuronal processes were found in the NAmb. Compared to controls (n=4), more c-Fos immunoreactivity, located principally in close proximity to fibers containing enkephalin was noted in the NAmb of EA-treated cats (n=5; P<0.01). Moreover, neurons double-labeled with c Fos and choline acetyltransferase in the NAmb were identified in EA-treated, but not control animals. These data demonstrate for the first time that EA activates preganglionic parasympathetic neurons in the NAmb. Because of their close proximity, these EA-activated neurons likely interact with nerve fibers containing enkephalin. These results suggest that EA at the P5-P6 acupoints has the potential to influence parasympathetic outflow and cardiovascular function, likely through an enkephalinergic mechanism. PMID- 22306034 TI - Towards molecular computing: co-development of microfluidic devices and chemical reaction media. AB - Microfluidics provides a powerful technology for both the production of molecular computing components and for the implementation of molecular computing architectures. The potential commercial applications of microfluidics drive rapid progress in this field-but at the same time focus interest on materials that are compatible with physiological aqueous conditions. For engineering applications that consider a broader range of physico-chemical conditions the narrow set of established materials for microfluidics can be a challenge. As a consequence of the large surface to volume ratio inherent in microfluidic technology the material of the device can greatly affect the chemistry in the channels of the device. In practice it is necessary to co-develop the chemical medium to be used in the device together with the microfluidic devices. We describe this process for a molecular computing architecture that makes use of excitable lipid-coated droplets of Belousov-Zhabotinsky reaction medium as its active processing components. We identify fluoropolymers with low melting temperature as a suitable substrate for microfluidics to be used in conjunction with Belousov-Zhabotinsky droplets in decane. PMID- 22306035 TI - An evaluation of interventions for reducing the risk of PRRSV introduction to filtered farms via retrograde air movement through idle fans. AB - Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically significant pathogen of pigs that can be transported via the airborne route out to 9.1 km. To reduce this risk, large swine facilities have started to implement systems to filter contaminated incoming air. A proposed means of air filtration failure is the retrograde movement of air (back-drafting) from the external environment into the animal air space through non-filtered points such as idle wall fans; however, this risk has not been validated. Therefore, the purpose of this study was threefold: (1) to prove that PRRSV introduction via retrograde air movement through idle fans is a true risk; (2) to determine the minimum retrograde air velocity necessary to introduce PRRSV to an animal airspace from an external source; and (3) to evaluate the efficacy of different interventions designed to reduce this risk. A retrograde air movement model was used to test a range of velocities and interventions, including a standard plastic shutter, a plastic shutter plus a canvas cover, a nylon air chute, an aluminum shutter plus an air chute and a double shutter system. Results indicated that retrograde air movement is a real risk for PRRSV introduction to a filtered air space; however, it required a velocity of 0.76 m/s. In addition, while all the interventions designed to reduce this risk were superior when compared to a standard plastic shutter, significant differences were detected between treatments. PMID- 22306036 TI - Herd-specific strains of Mycoplasma bovis in outbreaks of mycoplasmal mastitis and pneumonia. AB - Mycoplasma bovis causes severe economic losses in livestock production, particularly on the Northern American continent and more recently also in continental Europe. The aim of the current study was to evaluate whether the recently emerging outbreaks were due to a particular clone or strain of M. bovis or whether these outbreaks are due to multiple infectious strains of M. bovis. The study is based on the analysis M. bovis isolated from cattle of herds with outbreaks of mycoplasmal mastitis or pneumonia from geographically non related parts of Switzerland. M. bovis isolates were typed by insertion sequence (IS) element analysis based upon ISMbov1 and ISMbov2 southern-blot hybridization. We observed a strong divergence of M. bovis strains among affected herds which mostly were herd specific. This argues against the assumption that a recent infiltration of a particular clone of M. bovis is the cause of the perilous emerging outbreaks. The study suggests that transmission occurs from animal to animal most probably via milk. PMID- 22306037 TI - Clinical and virological outcome of an infection with the Belgian equine arteritis virus strain 08P178. AB - Equine viral arteritis (EVA) is an infectious disease with variable clinical outcome. Outbreaks, causing important economic losses, are becoming more frequent. Currently, there is a shortage of pathogenesis studies performed with European strains. In the present study, eight seronegative ponies were experimentally inoculated with the Belgian strain of equine arteritis virus (EAV) 08P178 (EU-1 clade) and monitored daily for clinical signs of EVA. Nasopharyngeal swabs, ocular swabs, bronchoalveolar cells and blood were collected for virological and serological testing. Two ponies were euthanized at 3, 7, 14, and 28 days post infection (DPI). After necropsy, specimens were collected for virus titration and immunofluorescence. EVA symptoms such as fever and lymphadenomegaly were evident from 3 to 10 DPI. Virus was isolated in nasal secretions from 2 to 9 DPI and in bronchoalveolar cells from 3 to 7 DPI. A cell-associated viraemia was detected from 3 to 10 DPI. After replication in the respiratory tract and draining lymph nodes, EAV reached secondary target organs (high virus titers in internal organs sampled at 7 DPI). At 14 DPI, virus titers dropped drastically and, at 28 DPI, only tonsils were positive. Immunofluorescence revealed both individual and clustered EAV-infected cells. Antibodies were detected starting from 7 DPI. It can be concluded that the Belgian strain 08P178 is a European mildly virulent subtype. At present, most European EAV strain infections were thought to run a subclinical course. This study is a proof that mildly virulent European EAV strains do exist in the field. PMID- 22306038 TI - Strawberry gingivitis. PMID- 22306039 TI - Colonic luminal surface retention of meloxicam microsponges delivered by erosion based colon-targeted matrix tablet. AB - The work was aimed at developing calcium-pectinate matrix tablet for colon targeted delivery of meloxicam (MLX) microsponges. Modified quassi-emulsion solvent diffusion method was used to formulate microsponges (MS), based on 3(2) full factorial design. The effects of volume of dichloromethane and EudragitRS100 content (independent variables) were determined on the particle size, entrapment efficiency and %cumulative drug release of MS1-MS9. The optimized formulation, MS5 (d(mean)=44.47 MUm, %EE=98.73, %CDR=97.32 and followed zero order release) was developed into colon-targeted matrix tablet using calcium pectinate as the matrix. The optimized colon-targeted tablet (MS5T2) shielded MLX loaded microsponges in gastrointestinal region and selectively delivered them to colon, as vizualized by vivo fluoroscopy in rabbits. The pharmacokinetic evaluation of MS5T2 in rabbits, revealed appearance of drug appeared in plasma after a lag time of 7h; a t(max) of 30 h with Fr=61.047%, thus presenting a formulation suitable for targeted colonic delivery. CLSM studies provided an evidence for colonic luminal retentive ability of microsponges at the end of 8h upon oral administration of MS5T2. Thus calcium pectinate matrix tablet loaded with MLX microsponges was developed as a promising system for the colon-specific delivery that has potential for use as an adjuvant therapy for colorectal cancer. PMID- 22306040 TI - Serum-stable, long-circulating paclitaxel-loaded colloidal carriers decorated with a new amphiphilic PEG derivative. AB - The paper describes sterically stabilized lipid nanocapsules (LNC) and multilamellar liposomes (MLV) coated using a new amphiphilic conjugate of PEG(2000) with a 2-alkyl-lipoamino acid (LAA). A complement activation assay (CH50) and uptake experiments by THP-1 macrophage cells were used to assess in vitro the effectiveness of the PEG-LAA derivative of modifying the surface behavior of nanocarriers. Administered to rats or Swiss mice, respectively, the PEG(2000)-LAA-modified LNC and MLV showed plasma half-lives longer than the corresponding naked carriers. To assess the ability of nanocarriers to specifically reach tumor sites, paclitaxel (PTX)-loaded LNC and MLV were administered subcutaneously to rats implanted with a 9L glioma. Animals treated with saline or naked LNC and MLV underwent a quick expansion of tumor mass, up to a volume of 2000 mm(3) 25 days after the injection of tumor cells. On the contrary, treatment with a PEG-LAA modified LNC carrier reduced the growth of the tumor volume, which did not exceed 1000 mm(3) by day 25. Analogous positive results were obtained with the liposomal systems. The experimental findings confirmed that these new PEG-LAA conjugates allow to obtain sterically stable nanocarriers that behave effectively and in a comparable or even better way than the (phospho)lipid PEG derivatives commercially available. PMID- 22306041 TI - In vitro sustained release of bioactive anti-NogoA, a molecule in clinical development for treatment of spinal cord injury. AB - Anti-NogoA is a promising anti-inhibitory molecule that has been shown to enhance functional recovery after spinal cord injury when delivered in rat and primate models over the span of weeks. To achieve this sustained release, anti-NogoA is typically delivered by osmotic minipumps; however, external minipumps are susceptible to infection. To address this issue, we developed a drug delivery system that consists of anti-NogoA-loaded poly(lactic-co-glycolic acid) nanoparticles dispersed in a hydrogel of hyaluronan and methylcellulose (composite HAMC). To optimize in vitro release, we screened formulations for improved anti-NogoA bioactivity and sustained release based on combinations of co encapsulated trehalose, hyaluronan, MgCO(3), and CaCO(3). Co-encapsulated MgCO(3) and CaCO(3) slowed the rate of anti-NogoA release and did not influence anti NogoA bioactivity. Co-encapsulated trehalose significantly improved anti-NogoA bioactivity at early release time points by stabilizing the protein during lyophilization. Co-encapsulated trehalose with hyaluronan improved bioactivity up to 28d and dramatically increased the rate and duration of sustained delivery. The sustained release of bioactive anti-NogoA from composite HAMC is a compelling formulation for in vivo evaluation in a model of spinal cord injury. PMID- 22306042 TI - Distribution of aerosols in mouse lobes by fluorescent imaging. AB - Better methods are needed to quantify the distribution of drug among the airways of the lungs of small animals to facilitate the development of agents that can target specific airways. Mice were exposed to aerosols of aluminum phthalocyanine tetrasulfonic acid (AlPCS) that ranged in concentration and size (0.2-2.8 MUm). The trachea and lobes were removed and placed between glass slides, and fluorescent images were obtained at two different compression thicknesses. The intensity, normalized by the area, exposure time, and thickness, was then plotted as a function of compression thickness, from which the concentration and attenuation coefficient were estimated for each lobe and then for each pixel of the image. The latter was then used to generate an image reflective of the concentration. The lobe volume, concentration, and tissue attenuation of AlPCS was consistent among the lobes. The deposition fraction increased with decreasing particle size. The network of lines in the concentration image indicated that connective tissue has a lower concentration. The central airways were clearly evident in the images of mice exposed to the very small and large aerosols. This approach provides a rapid, economical means to obtain high resolution images of mouse lungs from which detailed analysis of the distribution of deposited aerosol particles can be obtained. PMID- 22306043 TI - Implementing a cumulative supermatrix approach for a comprehensive phylogenetic study of the Teloschistales (Pezizomycotina, Ascomycota). AB - The resolution of the phylogenetic relationships within the order Teloschistales (Ascomycota, lichen-forming-fungi), with nearly 2000 known species and outstanding phenotypic diversity, has been hindered by the limitation in the resolving power that single-locus or two-locus phylogenetic studies have provided to date. In this context, an extensive taxon sampling within the Teloschistales with more loci (especially nuclear protein-coding genes) was needed to confront the current taxonomic delimitations and to understand evolutionary trends within this order. Comprehensive maximum likelihood and bayesian analyses were performed based on seven loci using a cumulative supermatrix approach, including protein coding genes RPB1 and RPB2 in addition to nuclear and mitochondrial ribosomal RNA coding genes. We included 167 taxa representing 12 of the 15 genera recognized within the currently accepted Teloschistineae, 22 of the 43 genera within the Physciineae, 49 genera of the closely related orders Lecanorales, Lecideales, and Peltigerales, and the dubiously placed family Brigantiaeaceae and genus Sipmaniella. Although the progressive addition of taxa (cumulative supermatrix approach) with increasing amounts of missing data did not dramatically affect the loss of support and resolution, the monophyly of the Teloschistales in the current sense was inconsistent, depending on the loci-taxa combination analyzed. Therefore, we propose a new, but provisional, classification for the re circumscribed orders Caliciales and Teloschistales (previously referred to as Physciineae and Teloschistineae, respectively). We report here that the family Brigantiaeaceae, previously regarded as incertae sedis within the subclass Lecanoromycetidae, and Sipmaniella, are members of the Teloschistales in a strict sense. Within this order, one lineage led to the diversification of the mostly epiphytic crustose Brigantiaeaceae and Letrouitiaceae, with a circumpacific center of diversity and found mostly in the tropics. The other main lineage led to another epiphytic crustose family, mostly tropical, and with an Australasian center of diversity--the Megalosporaceae--which is sister to the mainly rock inhabiting, cosmopolitan, and species rich Teloschistaceae, with a diversity of growth habits ranging from crustose to fruticose. Our results confirm the use of a cumulative supermatrix approach as a viable method to generate comprehensive phylogenies summarizing relationships of taxa with multi-locus to single locus data. PMID- 22306044 TI - Gastric pythiosis in a dog. AB - BACKGROUND: Pythiosis is caused by the agent Pythium insidiosum, an aquatic oomycete of the kingdom Stramenopila. AIMS: To describe the symptoms, pathological changes and diagnosis methods of gastric pythiosis in dogs. METHODS: A three-year-old female German shepherd, with access to wetlands, was attended due to vomiting and recurrent diarrhea of 30 days of duration. A palpable mass in the abdomen filling the left epigastric region was identified in the clinical examination. Simple and contrasted radiological examination and ultrasound of abdominal cavity were performed. The animal was referred for exploratory laparotomy for the removal of the mass. The extent of the mass prevented from the excision and the animal was euthanized. Samples of the tumor mass were collected and sent for morphological study and immunohistochemistry. RESULTS: The changes observed in imaging studies were consistent with gastric pythiosis. In cytology and histopathology, non-septate hyphae were identified, and in immunohistochemistry a strong positivity of anti-Pythium antibodies was observed, confirming the diagnosis of pythiosis. CONCLUSIONS: Pythiosis in dogs is diagnosed late and tends to evolve in the animal's death. The definitive diagnosis is by cytology, histology and immunohistochemistry. PMID- 22306045 TI - Hypoglycemia is associated with increased risk for brain injury and adverse neurodevelopmental outcome in neonates at risk for encephalopathy. AB - OBJECTIVE: To investigate the contribution of hypoglycemia in the first 24 hours after birth to brain injury in term newborns at risk for neonatal encephalopathy. STUDY DESIGN: A prospective cohort of 94 term neonates born between 1994 and 2010 with early postnatal brain magnetic resonance imaging studies were analyzed for regions of brain injury. Neurodevelopmental outcome was assessed at 1 year of age. RESULTS: Hypoglycemia (glucose <46 mg/dL) in the first 24 hours after birth was detected in 16% of the cohort. Adjusting for potential confounders of early perinatal distress and need for resuscitation, neonatal hypoglycemia was associated with a 3.72-fold increased odds of corticospinal tract injury (P=.047). Hypoglycemia was also associated with 4.82-fold increased odds of 1 point worsened neuromotor score (P=.038) and a 15-point lower cognitive and language score on the Bayley Scales of Infant Development (P=.015). CONCLUSION: Neonatal hypoglycemia is associated with additional risks in the setting of neonatal encephalopathy with increased corticospinal tract injury and adverse motor and cognitive outcomes. PMID- 22306046 TI - Lack of an effect of Lactobacillus reuteri DSM 17938 in preventing nosocomial diarrhea in children: a randomized, double-blind, placebo-controlled trial. AB - OBJECTIVE: To evaluate the efficacy of administering Lactobacillus reuteri DSM 17938 for the prevention of nosocomial diarrhea. STUDY DESIGN: Children (n = 106; aged 1-48 months) admitted to the hospital for reasons other than diarrhea were enrolled in a randomized, double-blind, placebo-controlled trial. They received L reuteri DSM 17938 at a dose of 10(8) colony-forming units (n = 54) or a placebo (n = 52) orally, once daily, for the duration of the hospital stay. RESULTS: Data from all children were included in the final analysis. L reuteri DSM 17938 did not significantly affect the risk of developing nosocomial diarrhea, defined as 3 loose or watery stools per day in a 24-hour period that occurred >72 hours after admission (risk ratio 1.06, 95% CI 0.7-1.5) or rotavirus infection (1.04, 0.6 1.6). There was also no difference between the probiotic and placebo groups for any of the other secondary outcomes (ie, incidence of rotavirus infection, incidence of diarrhea, duration of diarrhea, incidence of recurrent diarrhea, incidence of chronic diarrhea, length of hospital stay in days, and frequency of need for rehydration). No adverse events were reported. CONCLUSION: In hospitalized children, the administration of L reuteri DSM 17938 compared with placebo had no effect on the overall incidence of nosocomial diarrhea, including rotavirus infection. PMID- 22306047 TI - Pediatric sedation with propofol-continuing evolution of procedural sedation practice. PMID- 22306048 TI - Zinc protoporphyrin-to-heme ratios in high-risk and preterm infants. AB - OBJECTIVES: To refine the reference range for the zinc protoporphyrin-to-heme ratio (ZnPP/H) of preterm infants, we assessed the impact of maternal risk factors on ZnPP/H and evaluated the impact of changes in iron supplementation on iron status. STUDY DESIGN: The reference range for neonatal ZnPP/H was refined using prospective data from 31 reference infants <= 35 weeks' postmenstrual age (PMA) plus retrospective data from 51 infants <30 weeks' PMA, and 59 infants 30 40 weeks' PMA. Cord blood and first week of life values were compared when both were available. The impact of maternal risk factors was assessed by examining prospectively collected ZnPP/H from 48 high-risk infants. The effect of changing iron supplementation guidelines was evaluated by retrospective chart review of serial ZnPP/H from 194 infants. RESULTS: Cord ZnPP/H was lower at 30-35 weeks' gestation than at 24-26 weeks' gestation (P = .01). Cord ZnPP/H values from insulin-dependent diabetic mothers were elevated compared with reference values. Changing the iron supplementation protocol was not associated with improved ZnPP/H measurements. CONCLUSIONS: Cord blood and postnatal reference ranges for ZnPP/H are defined. Iron balance depends on a complex interaction of prenatal and postnatal factors. PMID- 22306049 TI - Intrahepatic lithiasis. PMID- 22306050 TI - MR Imaging of sclerosing cholangitis. AB - MRCP is a non-invasive cholangiographic technique used in detection and characterization of bile ducts abnormalities. MRCP features of primary sclerosing cholangitis are randomly distributed annular strictures alternating with slightly dilated bile ducts. Secondary sclerosing processes including ascending, ischemic, caustic, AIDS-related, eosinophilic and autoimmune cholangitis can mimic PSC at MRCP. PMID- 22306051 TI - Imaging features of primary pancreatic sarcomas. PMID- 22306052 TI - Auto-antibodies in autoimmune hepatitis: anti-soluble liver antigen (SLA). PMID- 22306053 TI - Expression of p53-MDM2 feedback loop related proteins in different gastric pathologies in relation to Helicobacter pylori infection: implications in gastric carcinogenesis. AB - AIM: To explore the association of p53-MDM2 feedback loop related proteins with gastric pathologies in relation to Helicobacter pylori infection. METHODS: Gastric biopsies were obtained from 157 H. pylori-negative and positive patients, including normal gastric mucosa (NGM), chronic gastritis (CG), intestinal metaplasia (IM), dysplasia (Dys), and gastric cancer (GC). The expression of mutant p53, MDM2, Bax and PUMA in gastric tissues was detected by immunohistochemistry. RESULTS: Overall expression of MDM2 and Bax is progressively increased from NGM to GC. PUMA expression is increased in CG but subsequently decreased after the development of IM. H. pylori infection is associated with increased mutant p53 and Bax expression but decreased PUMA expression in IM, and increased MDM2 expression in Dys. CONCLUSIONS: These results suggest that different p53-MDM2 feedback loop related proteins are distinctly expressed in the various stages of gastric carcinogenesis; their roles in gastric carcinogenesis in the presence of H. pylori infection need to be further investigated. PMID- 22306055 TI - PSC, AIH and overlap syndrome in inflammatory bowel disease. AB - Primary sclerosing cholangitis (PSC) is a progressive, cholestatic disorder characterised by chronic inflammation and stricture formation of the biliary tree. Symptoms include pruritus, fatigue and in advanced cases ascending cholangitis, cirrhosis and end-stage hepatic failure. Patients are at an increased risk of malignancy arising from the bile ducts, gallbladder, liver and colon. The majority (>80%) of Northern European patients with PSC also have inflammatory bowel disease (IBD), usually ulcerative colitis (UC). IBD commonly presents before the onset of PSC, although the opposite can occur and the onset of both conditions can be separated by many years. The colitis associated with PSC is characteristically mild although frequently involves the whole colon. Despite the majority of patients having relatively inactive colonic disease, paradoxically the risk of colorectal malignancy is substantially increased. Patients may also develop dominant, stenotic lesions of the biliary tree which may be difficult to differentiate from cholangiocarcinoma and the coexistence of IBD may influence the development of this complication. Ursodeoxycholic acid may offer a chemoprotective effect against colorectal malignancy and improve liver biochemical indices. Evidence of any beneficial effect on histological progression of hepatobiliary disease is less clear. High doses (~25-30 mg/kg/d) may be harmful and should be avoided. Autoimmune hepatitis (AIH) is less common in patients with IBD than PSC, however, an association has been observed. A small subgroup may have an overlap syndrome between AIH and PSC and management should be individualised dependant on liver histology, serum immunoglobulin levels, autoantibodies, degree of biochemical cholestasis and cholangiography. PMID- 22306056 TI - B cell-intrinsic MyD88 signaling prevents the lethal dissemination of commensal bacteria during colonic damage. AB - The Toll-like receptor adaptor protein MyD88 is essential for the regulation of intestinal homeostasis in mammals. In this study, we determined that Myd88 deficient mice are susceptible to colonic damage that is induced by dextran sulfate sodium (DSS) administration resulting from uncontrolled dissemination of intestinal commensal bacteria. The DSS-induced mortality of Myd88-deficient mice was completely prevented by antibiotic treatment to deplete commensal bacteria. By using cell type-specific Myd88-deficient mice, we established that B cell intrinsic MyD88 signaling plays a central role in the resistance to DSS-induced colonic damage via the production of IgM and complement-mediated control of intestinal bacteria. Our results indicate that the lack of intact MyD88 signaling in B cells, coupled with impaired epithelial integrity, enables commensal bacteria to function as highly pathogenic organisms, causing rapid host death. PMID- 22306057 TI - Pool-independent labelling of synaptic vesicle exocytosis with single vesicle resolution in rat hippocampal neurons. AB - FM dyes are an established tool to analyze synaptic vesicle pools. However, quantitative measurements using FM dyes are typically based on the re-release properties of previously labelled vesicles, which might vary depending on the experimental setup. An FM dye protocol independent of the previous labelling of vesicle membrane has not been applied for quantitative measurements of individual synaptic vesicles before. We therefore analyzed the direct staining of newly exocytosed vesicle membrane with FM dyes in cultured rat hippocampal neurons. In the presence of FM 1-43, stimulation-induced synaptic activity led to a stable fluorescence increase. The quantal release of synaptic vesicles was preserved and its amplitude correlated highly with the exocytic dye loss induced by a subsequent stimulation. Thus, the method presented here provides a tool for the pool-independent measurement of synaptic vesicle exocytosis. PMID- 22306054 TI - Epidemiology and adherence to guidelines on the management of bleeding peptic ulcer: a prospective multicenter observational study in 1140 patients. AB - BACKGROUND AND OBJECTIVE: Mortality of upper gastrointestinal bleeding seems declining. Whether practice guidelines for the management of peptic ulcer bleeding are followed is unknown. We aimed to update epidemiology of peptic ulcer bleeding and to assess the adherence to guidelines in the French community. METHODS: Between March, 2005 and February, 2006, a prospective multicenter study was conducted including all patients with communautary upper gastrointestinal bleeding. Data from patients with peptic ulcer bleeding were extracted and analyzed. RESULTS: Out of 3203 analyzable patients included, 1140 (35.6%) had a peptic ulcer bleeding and 965 of them a duodenal and/or gastric ulcer. Seven hundred and thirty-five were male (64.5%) and mean age was 66.4 years (+/-18.8). Overall, 699 patients (61.3%) were taking medication inducing upper gastrointestinal bleeding. Two-hundred and sixty-eight (23.5%) patients had endoscopic therapy, 190 (70.9%) of whom had epinephrine injection alone. Among the 349 patients with high risk stigmata on endoscopy (Forrest IA, IB, IIA), 209 (59.9%) underwent endoscopic therapy. One thousand one hundred and seven patients (97.1%) were given proton-pump inhibitors. One hundred and thirty-four patients (11.8%) experienced haemorrhagic recurrence. Forty-eight patients (4.2%) underwent surgery and 61 (5.4%) died. CONCLUSIONS: Consistently with previous studies, mortality of upper gastrointestinal bleeding seems declining. Further progress lies above all in prevention but also probably in better adherence to therapeutic guidelines and management of comorbidities. PMID- 22306058 TI - Hypoglycaemia and cardiovascular disease in Type 1 Diabetes. Results from the Catalan National Public Health registry on insulin pump therapy. AB - Severe hypoglycaemia has recently been associated with an increased risk for cardiovascular disease (CVD) in diabetes. The retrospective analysis of a national registry on continuous subcutaneous insulin infusion points to a higher prevalence of CVD in Type 1 diabetic subjects with repeated severe hypoglycaemia at the time of starting CSII. PMID- 22306059 TI - Diabetic ketoacidosis accompanied by hypothermia: a case report. AB - Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of diabetes mellitus and is caused by insulin insufficiency. Hypothermia is defined as a core temperature of less than 35 degrees C and is sometimes accompanied by DKA. We report two patients with diabetes who were admitted for DKA accompanied by hypothermia. PMID- 22306060 TI - Feasibility, reliability and validity of the Iranian version of the Diabetes Quality of Life Brief Clinical Inventory (IDQOL-BCI). AB - AIMS: To validate and culturally adapt the Diabetes-specific Quality of Life Brief Clinical Inventory (DQOL-BCI) for the Iranian population. METHODS: After translation - back translation, content validity was assessed utilizing a panel of six experts. Based on a sample of 180 diabetic patients referred to two Diabetics Clinic Centers from September to May 2011 in Karaj, Iran, construct validity via detecting the factor structure, and convergent and discriminant validity were evaluated by scale-item correlations and known group analyses. Internal consistency and test-retest reliability were assessed in sample of 30 patients by Cronbach's and intraclass correlation coefficient (ICC). RESULTS: The IDQOL-BCI showed good content validity (CVI values>0.75 and CVR values>0.99), internal consistency (alpha=0.75) and test-retest reliability (ICC=0.81). A 3 factor solution was found. In addition, high values of item-scale correlations confirmed the convergence validity, and some subscales and total scores differentiate between groups defined by sex, disease duration, income levels, drug using status and physical activity demonstrated the discriminant validity. CONCLUSIONS: Our findings demonstrate the initial feasibility, reliability and validity of the Iranian version of the IDQOL-BCI as a measure of diabetic specific QOL measure in Iranian patients. PMID- 22306061 TI - A system for automated tracking of motor components in neurophysiological research. AB - In the study of motor systems it is often necessary to track the movements of an experimental animal in great detail to allow for interpretation of recorded brain signals corresponding to different control signals. This task becomes increasingly difficult when analyzing complex compound movements in freely moving animals. One example of a complex motor behavior that can be studied in rodents is the skilled reaching test where animals are trained to use their forepaws to grasp small food objects, in many ways similar to human hand use. To fully exploit this model in neurophysiological research it is desirable to describe the kinematics at the level of movements around individual joints in 3D space since this permits analyses of how neuronal control signals relate to complex movement patterns. To this end, we have developed an automated system that estimates the paw pose using an anatomical paw model and recorded video images from six different image planes in rats chronically implanted with recording electrodes in neuronal circuits involved in selection and execution of forelimb movements. The kinematic description provided by the system allowed for a decomposition of reaching movements into a subset of motor components. Interestingly, firing rates of individual neurons were found to be modulated in relation to the actuation of these motor components suggesting that sets of motor primitives may constitute building blocks for the encoding of movement commands in motor circuits. The designed system will, thus, enable a more detailed analytical approach in neurophysiological studies of motor systems. PMID- 22306062 TI - Dental pulp can be a good candidate for nerve grafting in a xeno-graft model. AB - Dental pulp is discarded after extirpation of dental pulp and after tooth extraction. However, it contains nerve tissue abundantly and could be used more effectively. This study was designed to examine whether a dental pulp could be a candidate of donor for nerve grafting in xenografting model. The dental pulp was obtained from a human vital extracted tooth for orthodontic treatment, and treated with freezing and thawing method for reducing antigenicity. The treated sample was inserted into chitosan mesh tube for easy suturing, and then the complex was implanted into transected sciatic nerve in Sprague-Dawley (SD) rats (dental pulp group). As controls, chitosan tubes with and without sciatic nerve harvested from another SD rats were implanted (isograft group and tube group, respectively). As early as 4 weeks after grafting, regenerating axons accompanied by host Schwann cells were found to grout out through basal laminae by electron microscopy. The intact structure of basal laminae at this period suggested that they were derived from the original structure of donor graft. Twelve weeks after grafting, sporadic axonal regeneration was confirmed by light microscopy in the dental pulp group. Thirty-two weeks after implantation, aggregation of axons was observed in this group and matched that in isograft group. The average diameter of axons in dental pulp group was comparable to that in isograft group, whereas number of minifascicles and axon proportion were smaller. It was suggested that some delay occurred in dental pulp group because of the phagocytosis and absorption of tissue debris components remained after the freezing and thawing treatment. These findings clearly demonstrate that even dental pulp can act as conduits for regenerating axons. PMID- 22306063 TI - Spontaneous synchronized burst firing of subthalamic nucleus neurons in rat brain slices measured on multi-electrode arrays. AB - The current study presents an organotypic rat midbrain slice culture that served as a consistent and informative framework, where the STN neurons and their interconnectivity were closely examined with respect to electrophysiological and pharmacological properties. From multi-electrode array recordings, it was found that the majority of STN neurons spontaneously fired in bursts rather than tonically under control conditions, and the neural activity between pairs of burst-firing STN neurons was tightly correlated. This spontaneous synchronized burst firing was also affected by a glutamate receptor antagonist, yet unaffected by a GABA receptor antagonist. Moreover, even when the STN was isolated from all its known external inputs, spontaneous synchronized burst firing was still observed under control conditions and consistently switched to tonic firing following the application of a glutamate receptor antagonist. Therefore, the results indicated the existence of glutamatergic projections to the STN in the slice preparation, and these excitatory synaptic connections appeared to originate from axon collaterals within the STN rather than other basal ganglia nuclei. It could be concluded that the STN neurons and their interconnectivity are essential requirements in the rat brain slice preparation to produce spontaneous synchronized burst firing. PMID- 22306064 TI - Evaluating imaging and computer-aided detection and diagnosis devices at the FDA. AB - This report summarizes the Joint FDA-MIPS Workshop on Methods for the Evaluation of Imaging and Computer-Assist Devices. The purpose of the workshop was to gather information on the current state of the science and facilitate consensus development on statistical methods and study designs for the evaluation of imaging devices to support US Food and Drug Administration submissions. Additionally, participants expected to identify gaps in knowledge and unmet needs that should be addressed in future research. This summary is intended to document the topics that were discussed at the meeting and disseminate the lessons that have been learned through past studies of imaging and computer-aided detection and diagnosis device performance. PMID- 22306065 TI - Production and characterization of Clostridium perfringens recombinant beta toxoid. AB - In this work, we produced and evaluated a vaccine based on a beta toxoid of Clostridium perfringens type C produced in Escherichia coli (rBT). The non-toxic rBT was innocuous for mice and induced 14 IU mL(-1) of beta antitoxin in rabbits, complying with the European Pharmacopeia and CFR9 - USDA guidelines. PMID- 22306066 TI - Anthracenedione-methionine conjugates are novel topoisomerase II-targeting anticancer agents with favorable drug resistance profiles. AB - Structure-associated drug resistance and DNA-unwinding abilities have greatly limited the clinical usage of anthracenediones, including mitoxantrone (MX) and ametantrone (AT), which intercalate into DNA and induce topoisomerase II (TOP2) mediated DNA break. We studied a series of 1,4-bis(2-amino-ethylamino) MX- and AT amino acid conjugates (M/AACs) and showed that abilities in cancer cell killing correlate with the amounts of chromosomal DNA breaks induced by M/AACs. Notably, the 1,4-bis-L/l-methionine-conjugated MAC (L/LMet-MAC) exhibits DNA-breaking, cancer cell-killing and anti-tumor activities rivaling those of MX. Interestingly, l- and d-form Met-M/AACs unwind DNA poorly compared to MX and AT. The roles of the two human TOP2 isozymes (hTOP2alpha and 2beta) in the L/LMet-MAC induced DNA breakage and cancer cell-killing were suggested by the following observations: (i) M/AAC-induced DNA breakage, cytotoxicity and apoptosis are greatly reduced in various TOP2-deficient conditions; (ii) DNA breaks induced by MACs are highly reversible and effectively antagonized by the TOP2 catalytic inhibitors; (iii) MACs induced differential TOP2-mediated DNA cleavage in vitro using recombinant hTOP2alpha proteins and the formation of hTOP2alpha/betacc in the cell culture system. Interestingly, d-aa-conjugated MACs often caused a lower level in hTOP2-mediated DNA breaks and cell-killing than the corresponding l-form ones indicating a steric-specific effect of MACs. Together, our results suggest that both enzyme- and DNA-drug interactions might contribute to TOP2-targeting by M/AACs. Furthermore, Met-MACs are poor substrates for the MDR1 transporter. Therefore, L/LMet-MAC represents a promising class of TOP2-targeting drugs with favorable drug resistance profiles. PMID- 22306067 TI - Acute sensitization of colon cancer cells to inflammatory cytokines by prophase arrest. AB - Understanding how colon cancer cells survive within the inflammatory milieu of a tumor, and developing approaches that increase their sensitivity to inflammatory cytokines, may ultimately lead to novel approaches for colon cancer therapy and prevention. Analysis of a number of chemopreventive and therapeutic agents reveal that HDAC inhibitors are particularly adept at sensitizing colon cancer cells TNF or TRAIL mediated apoptosis. In vivo data are consistent with an interaction between SAHA and TNF in inducing apoptosis, as AOM-induced colon tumors express elevated levels of TNF and are more sensitive to SAHA administration. Cell cycle analysis and time-lapse imaging indicated a close correspondence between SAHA induced prophase arrest and TNF or TRAIL-induced apoptosis. Prophase arrest induced by the Aurora kinase inhibitor VX680 likewise sensitized cells to TNF and TRAIL, with siRNA analysis pointing to Aurora kinase A (and not Aurora kinase B) as being the relevant target for this sensitization. We propose that agents that promote prophase arrest may help sensitize cancer cells to TNF and other inflammatory cytokines. We also discuss how circumvention of an early mitotic checkpoint may facilitate cancer cell survival in the inflammatory micro environment of the tumor. PMID- 22306068 TI - Dermacentor variabilis: characterization and modeling of macrophage migration inhibitory factor with phylogenetic comparisons to other ticks, insects and parasitic nematodes. AB - We have identified and characterized the full length cDNA sequence of macrophage migration inhibitory factor (MIF) from the American dog tick, Dermacentor variabilis. The nucleotide and putative amino acid sequences from this study shared a high level of sequence conservation with other tick MIFs. The bioinformatics analysis showed across species conservation of the MIF amino acid sequence in ticks, insects and nematodes. The multiple sequence alignment identified Pro 1, 3, 55; Thr 7, 112; Asn 8, 72; Ile 64, 96; Gly 65, 110, Ser 63 and Leu 87 amino acids to be highly conserved among the sequences selected for this study. Tick MIF does not have the oxidoreductase domain as found in MIFs from other animals suggesting that tick MIF is not capable of performing as an oxidoreductase. The phylogenetic analysis revealed that tick MIFs share a closer evolutionary proximity to parasitic nematode MIFs than to insect MIFs. PMID- 22306069 TI - Characterization of a compensatory mutant of Leishmania major that lacks ether lipids but exhibits normal growth, and G418 and hygromycin resistance. AB - Ether glycerolipid biosynthesis in Leishmania major initiates with the acylation of dihydroxyacetonephosphate by the glycosomal dihydroxyacetonephosphate acyltransferase LmDAT. We previously reported that a null mutant of LmDAT is severely affected in logarithmic growth, survival during stationary phase, and in virulence in mice. In addition, it lacks all ether glycerolipids, produces altered forms of the ether-lipid based virulence factors lipophosphoglycan and increased levels of GPI-anchored protein gp63. Here, we describe the characterization of a compensatory mutant of a null strain of LmDAT, Deltalmdat/Deltalmdat(rev). Similarly to the null mutant, the Deltalmdat/Deltalmdat(rev) strain formed altered forms of lipophosphoglycan and increased levels of gp63, and was avirulent in mice infection. Further, dihydroxyacetonephosphate acyltransferase activity was absent in the revertant clone, indicating that a mutation in another acyltransferase gene did not confer dihydroxyacetonephosphate specificity. In contrast, the revertant grew normally but still exhibited poor survival during stationary phase. In addition, agarose gel analysis of its genomic DNA failed to detect any amplified DNA. Surprisingly, its sensitivity to aminoglycoside based antibiotics G418 and hygromycin was lower than that of the null mutant, wild type and complemented line. PMID- 22306070 TI - Toxoplasma gondii antigens: recovery analysis of tachyzoites cultivated in Vero cell maintained in serum free medium. AB - Vero cells have been used successfully in Toxoplasma gondii maintenance. Medium supplementation for culture cells with fetal bovine serum is necessary for cellular growth. However, serum in these cultures presents disadvantages, such as the potential to induce hypersensitivity, variability of serum batches, possible presence of contaminants, and the high cost of good quality serum. Culture media formulated without any animal derived components, designed for serum-free growth of cell lines have been used successfully for different virus replication. The advantages of protozoan parasite growth in cell line cultures using serum-free medium remain poorly studied. Thus, this study was designed to determine whether T. gondii tachyzoites grown in Vero cell cultures in serum-free medium, after many passages, are able to maintain the same antigenic proprieties as those maintained in experimental mice. The standardization of Vero cell culture in serum-free medium for in vitro T. gondii tachyzoite production was performed establishing the optimal initial cell concentration for the confluent monolayer formation, which was 1*10(6) Vero cell culture as initial inoculum. The total confluent monolayer formatted after 96 h and the best amount of harvested tachyzoites was 2.1*10(7) using parasite inoculum of 1.5*10(6) after 7 days post infection. The infectivity of tachyzoites released from Vero cells maintained in serum-free medium was evaluated using groups of Swiss mice infected with cell culture tachyzoites. The parasite concentrations were similar to those for mice infected with tachyzoites collected from other infected mice. The data from both in vivo and in vitro experiments showed that in at least 30 culture cell passages, the parasites maintained the same infectivity as maintained in vivo. Another question was to know whether in the several continued passages, immunogenic progressive loss could occur. The nucleotide sequences studied were the same between the different passages, which could mean no change in their viability in the lysate antigen. Thus, the antigen production by cell culture has clear ethical and cost-saving advantages. Moreover, the use of culture media formulated without any human or animal derived components, designed for serum free growth of cell lines, successfully produced tachyzoites especially for antigen production. PMID- 22306071 TI - Increasing sensitivity in the measurement of heart rate variability: the method of non-stationary RR time-frequency analysis. AB - A novel method of the time-frequency analysis of non-stationary heart rate variability (HRV) is developed which introduces the fragmentary spectrum as a measure that brings together the frequency content, timing and duration of HRV segments. The fragmentary spectrum is calculated by the similar basis function algorithm. This numerical tool of the time to frequency and frequency to time Fourier transformations accepts both uniform and non-uniform sampling intervals, and is applicable to signal segments of arbitrary length. Once the fragmentary spectrum is calculated, the inverse transform recovers the original signal and reveals accuracy of spectral estimates. Numerical experiments show that discontinuities at the boundaries of the succession of inter-beat intervals can cause unacceptable distortions of the spectral estimates. We have developed a measure that we call the "RR deltagram" as a form of the HRV data that minimises spectral errors. The analysis of the experimental HRV data from real-life and controlled breathing conditions suggests transient oscillatory components as functionally meaningful elements of highly complex and irregular patterns of HRV. PMID- 22306072 TI - Segmentation of cervical cell nuclei in high-resolution microscopic images: A new algorithm and a web-based software framework. AB - In order to automate cervical cancer screening tests, one of the most important and longstanding challenges is the segmentation of cell nuclei in the stained specimens. Though nuclei of isolated cells in high-quality acquisitions often are easy to segment, the problem lies in the segmentation of large numbers of nuclei with various characteristics under differing acquisition conditions in high resolution scans of the complete microscope slides. We implemented a system that enables processing of full resolution images, and proposes a new algorithm for segmenting the nuclei under adequate control of the expert user. The system can work automatically or interactively guided, to allow for segmentation within the whole range of slide and image characteristics. It facilitates data storage and interaction of technical and medical experts, especially with its web-based architecture. The proposed algorithm localizes cell nuclei using a voting scheme and prior knowledge, before it determines the exact shape of the nuclei by means of an elastic segmentation algorithm. After noise removal with a mean-shift and a median filtering takes place, edges are extracted with a Canny edge detection algorithm. Motivated by the observation that cell nuclei are surrounded by cytoplasm and their shape is roughly elliptical, edges adjacent to the background are removed. A randomized Hough transform for ellipses finds candidate nuclei, which are then processed by a level set algorithm. The algorithm is tested and compared to other algorithms on a database containing 207 images acquired from two different microscope slides, with promising results. PMID- 22306073 TI - Hierarchical pose estimation for human gait analysis. AB - Articulated structures like the human body have many degrees of freedom. This makes an evaluation of the configuration's likelihood very challenging. In this work we propose new linked hierarchical graphical models which are able to efficiently evaluate likelihoods of articulated structures by sharing visual primitives. Instead of evaluating all configurations of the human body separately we take advantage of the fact that different configurations of the human body share body parts, and body parts, in turn, share visual primitives. A hierarchical Markov random field is used to integrate the sharing of visual primitives in a probabilistic framework. We propose a scalable hierarchical representation of the human body and show that this representation is especially well suited for human gait analysis from a frontal camera perspective. Furthermore, the results of the evaluation on a gait dataset show that sharing primitives substantially accelerates the evaluation and that our hierarchical probabilistic framework is a robust method for scalable detection of the human body. PMID- 22306074 TI - Use of an osmotically sensitive mutant of Propionibacterium freudenreichii subspp. shermanii for the simultaneous productions of organic acids and trehalose from biodiesel waste based crude glycerol. AB - Recently suitability of crude glycerol for trehalose and propionic acid productions was reported using Propionibacterium freudenreichii subspp. shermanii and it was concluded that presence of KCl in crude glycerol was the probable reason for higher trehalose accumulation with crude glycerol medium. To further improve trehalose production, an osmotic sensitive mutant of this strain (non viable in medium with 3% NaCl) with higher trehalose yield was isolated. In mutant, trehalose yields achieved with respect to biomass and substrate consumed (391 mg/g of biomass, 90 mg/g of substrate consumed) were three and four times higher, respectively as compared to parent strain when crude glycerol was used as a carbon source. Other major fermentation products obtained were propionic acid (0.42 g/g of substrate consumed) and lactic acid (0.3g/g of substrate consumed). It was also observed that in mutant higher activity of ADP-glucose pyrophosphorylase was probably responsible for higher trehalose accumulation. PMID- 22306075 TI - Synergistic conversion of glucose into 5-hydroxymethylfurfural in ionic liquid water mixtures. AB - A method for converting glucose into 5-hydroxymethylfurfural (5-HMF) without using chromium-containing catalysts was developed. The method uses ionic liquid water mixtures with a ZrO(2) catalyst. Addition of a certain amount of water (10 50 wt.%) into the 1,3-dialkylimidazolium chloride ionic liquid promoted the formation of 5-HMF from glucose compared with that in either pure water or in the pure ionic liquid. A 5-HMF yield of 53% was obtained within 10 min at 200 degrees C in a 50:50 w/w% 1-hexyl-3-methyl imidazolium chloride-water mixture in the presence of ZrO(2). The 1,3-dialkylimidazolium ionic liquids having Cl(-) or HSO(4)(-) anions were effective for promoting 5-HMF formation. Addition of protic solvents such as methanol and ethanol to the ionic liquid had a similar synergistic effect as water and promoted fructose and 5-HMF formation. The results reported in this work can be extended to other fields, where the ratio of ionic liquid and protic solvent can be adjusted to promote the desired reactions. PMID- 22306076 TI - Thermal decomposition of wood: influence of wood components and cellulose crystallite size. AB - The influence of wood components and cellulose crystallinity on the thermal degradation behavior of different wood species has been investigated using thermogravimetry, chemical analysis and X-ray diffraction. Four wood samples, Pinus elliottii (PIE), Eucalyptus grandis (EUG), Mezilaurus itauba (ITA) and Dipteryx odorata (DIP) were used in this study. The results showed that higher extractives contents associated with lower crystallinity and lower cellulose crystallite size can accelerate the degradation process and reduce the wood thermal stability. On the other hand, the thermal decomposition of wood shifted to higher temperatures with increasing wood cellulose crystallinity and crystallite size. These results indicated that the cellulose crystallite size affects the thermal degradation temperature of wood species. PMID- 22306077 TI - Hydrogen production and microbial diversity in sewage sludge fermentation preceded by heat and alkaline treatment. AB - Combined pretreatment of heat treatment with alkaline condition was applied to the sewage sludge in order to acquire the effective method for sludge solubilization and bio-hydrogen production. Solubilization ratio of the sludge with heat treatment at alkaline condition (pH 13) was as high as 85.0%, resulting in an increase of COD concentration in aqueous solution, but the ratio of sludge with heat treatment or alkaline treatment alone was 32.2% and 56.3%, respectively. During the fermentation of the pretreated sludge, a significant increase of hydrogen production was observed with a low strength of ammonia, showing that ammonia in the aqueous phase could inhibit bio-hydrogen production. Klebsiella, Enterobacter or Clostridium genus were mostly related on the hydrogen production. PMID- 22306078 TI - Sequential acid-/alkali-pretreatment of empty palm fruit bunch fiber. AB - Pretreatment processes are key technologies for generating fermentable sugars based on lignocellulosic biomass. In this study, we developed a novel method for empty palm fruit bunch fiber (EPFBF) using sequential pretreatment with dilute acid and then alkali. Dilute sulfuric acid was used in the first step, which removed 90% of the hemicellulose and 32% of the lignin, but left most of the cellulose under the optimum pretreatment condition. Sodium hydroxide was then applied in the second step, which extracted lignin effectively with a 70% delignification yield, partially disrupting the ordered fibrils of the EPFBF and thus enhancing the enzyme digestibility of the cellulose. The sequentially pretreated biomass consisted of 82% cellulose, less than 1% hemicellulose, and 30% lignin content afterward. The pretreated biomasses morphologically revealed rough, porous, and irregularly ordered surfaces for enhancing enzyme digestibility. These results indicate that the sequentially acid/alkali pretreated EPFBF could be broadly useful as a novel biomass. PMID- 22306079 TI - Comparison of alkaline- and fungi-assisted wet-storage of corn stover. AB - Storage of lignocellulosic biomass is critical for a year-round supply of feedstock for a biorefinery. Compared with dry storage, wet storage is a promising alternative technology, providing several advantages including reduced dry matter loss and fire risk and improved feedstock digestibility after storage. This study investigated the concurrent pretreatment and wet-storage of corn stover with the assistance of NaOH or a lignin-degrading fungus, Ceriporiopsis subvermispora, during a 90-d period. Compared with ensilage, adding NaOH or inoculation with C. subvermispora significantly enhanced the enzymatic degradability of corn stover by 2-3-fold after 90-d wet storage. Lignin and xylan removal during NaOH pretreatment and wet-storage were influenced by NaOH loading and moisture. NaOH pretreatment retarded the production of organic acids during storage and the acetate release correlated with lignin and xylan removal. Further study is needed to reduce cellulose degradation during the late stage of fungal treatment. PMID- 22306080 TI - Localization and developmental expression patterns of CSPG-cs56 (aggrecan) in normal and dystrophic retinas in two rat strains. AB - Proteoglycans have a number of important functions in the central nervous system. Aggrecan (hyaluronan-binding proteoglycan, CSPG-cs56) is found in the extracellular matrix of cartilage as well as in the developing brain. We compared the postnatal distribution of CSPG-cs56 in Long Evans (LE) and Royal College of Surgeons (RCS) rat retinas to determine if this proteoglycan played a role in the development of dystrophic retinas. CSPG-cs56 expression was examined in rat retinas aged between birth (postnatal day 0, P0) and P150 using immunofluorescence and Western-blots. Immunofluorescence was quantified using ImageJ. GFAP staining was used to compare Muller cell labeling and the distribution of CSPG-cs56. Both rat strains showed a significant rise in total retinal CSPG-cs56 between P0 and P21; values peaked on P21 in LE rats and P14 in RCS rats. CSPG-cs56 then significantly decreased to lower levels (P35) in both strains before reaching significantly higher levels by P90-P150. CSPG-cs56 positive staining was present in the ganglion cell layer at birth and clear layering of the inner plexiform layer was seen between P7 and P21 due to dendritic staining of retinal ganglion cells. Staining was less intense and diffuse within the outer plexiform over a similar time-course. Light CSPG-cs56 labeling in the region of the outer segments was present at (P14) and became more intense as the retina approached maturity. CSPG-cs56 in the outer segments was the main contributor to the higher expression in older animals. Substantial differences in CSPG-cs56 labeling were not seen between LE and RCS rats. There was no evidence to suggest that Muller cells were the source of CSPG-cs56 in either rat strain, although their staining distributions had a degree of overlap. The lack of significant differences between LE and RCS rats indicates that CSPG cs56 may not be involved in the degenerative process or the reorganization of the RCS rat retina. We suggest that the main role of CPSG-cs56 is to maintain retinal ganglion cell dendritic structure in the inner plexiform layer and is closely related to providing adequate support and flexibility for the photoreceptor outer segments, which is necessary to maintain their function. PMID- 22306081 TI - Microbial activity and diversity in long-term mixed contaminated soils with respect to polyaromatic hydrocarbons and heavy metals. AB - The co-occurrence of polyaromatic hydrocarbons (PAHs) with heavy metals and their effect on soil microbial activity have not been systematically investigated. In this study a holistic approach was employed by combining physico-chemical, biological and advanced molecular methods to determine the soil microbial activities of long-term mixed contaminated soils collected from a former manufactured gas plant (MGP) site. Concentrations of PAHs in MGP soils ranged from 335 to 8645 mg/kg. Of the potentially toxic metals, concentrations of lead were found to be highest, ranging from 88 to 671 mg/kg, cadmium 8 to 112 mg/kg, while zinc varied from 64 to 488 mg/kg. The enzyme activities were severely inhibited in soils that were contaminated with both PAHs and heavy metals. The presence of heavy metals in PAH-contaminated soils not only reduced the diversity of microbial population but also showed a few distinctive species by exerting selective pressure. The multivariate analysis revealed that there is an association between PAHs and heavy metals which influenced biological properties in mixed contaminated soils. The findings of this study have major implications for the bioremediation of organic pollutants in metal-organic mixed contaminated sites. PMID- 22306082 TI - A nationwide production analysis of state park attendance in the United States. AB - This study examined the production of U.S. states' park visits from 1984 to 2010 by state. In specifying the production equation in terms of the influences of the states' parklands, labor, and capital investments on the annual attendances, we found that state governments will experience an ongoing need for more labor to maintain their parklands if attendance is to increase in the future. Results also indicated that more capital expenditures are not likely to increase park utilization rates. Post-estimation procedures involved the application of the response residuals to identify the capacity utilization rates of the states' park systems over the past 27 years. Past utilization rates revealed operators met or exceeded capacity utilization expectations from 1984 through 1990. However, beginning in 1991, the annual mean utilization rate for the nation's supply of states' parks signaled a trend toward excess capacity. Our forecast revealed the mean utilizations over the next three years will vary between 90% and 95%. Post estimation procedures also examined the relationship between state park management orientations (towards either public-lands preservation or recreational development) and projected annual capacity utilization rates. Results indicate that the quantity of added facilities to broaden their appeal to the public (i.e., a recreation orientation) was not important in explaining utilization capacities. However, an orientation toward public-lands preservation related significantly to greater utilization rates. In our view, the public will continue to accept current cost structures for continued operations of the states' parks on the compelling need for access to outdoor recreation to contribute to the visitor well-being. PMID- 22306083 TI - 17beta-Estradiol activates GPER- and ESR1-dependent pathways inducing apoptosis in GC-2 cells, a mouse spermatocyte-derived cell line. AB - In mammals, spontaneous apoptosis is observed particularly in differentiating spermatogonia and in spermatocytes. 17beta-Estradiol (E2) in primary rat pachytene spermatocytes (PS) binds estrogen receptor alpha (ESR1) and GPER to activate EGFR/ERK/c-Jun pathway leading to up regulation of proapoptotic factor bax. Aim of this study was to clarify the effector pathway(s) controlling spermatocytes apoptosis using as model GC-2 cells, an immortalized mouse pachytene spermatocyte-derived cell line, which reproduces primary cells responses to E2. In fact, in GC-2 cells we observed that ESR1 and GPER activation caused rapid ERK and c-Jun phosphorylation, bax up-regulation, events associated with apoptosis. We further investigated the apoptotic mechanism demonstrating that E2, as well as ESR1 and GPER specific agonists, induced sustained ERK, c-Jun and p38 phosphorylation, Cytochrome c release, caspase 3 and endogenous substrate Poly (ADP-ribose) polymerase (PARP) activation and increased expression of cell cycle inhibitor p21. When ESR1 or GPER expression was silenced, E2 was still able to decrease cell proliferation, only the concomitant silencing abolished E2 effect. These results indicate that GC-2 cells are a valid cell model to study E2 dependent apoptosis in spermatocytes and show that E2, activating both ESR1 and GPER, is able to induce an ERK1/2, c-Jun and p38-dependent mitochondrion apoptotic pathway in this cell type. PMID- 22306084 TI - Functional melanocortin-2 receptors are expressed by mouse aorta-derived mesenchymal progenitor cells. AB - A local melanocortin system is active during tissue injury and inflammation. Thus far this system has been described as autocrine in nature where local production of pro-opiomelanocortin (POMC) peptides by leukocytes feeds back on melanocortin receptor (MC-R) expressing immune cells to quell inflammatory cytokine production. Here we present evidence that POMC peptides may generate extracellular matrix (ECM) changes by inducing matrix production by cells of the mesenchymal lineage through activation of the MC2-R. Using immunoblot, we determined that mouse aorta-derived mesenchymal progenitor cells express both MC2 R and MC3-R. These progenitors respond to treatment with ACTH by increasing collagen matrix synthesis as assessed by picrosirius red stain and (3)H-proline incorporation. ACTH also induces transient increases in intracellular calcium ([Ca(2+)](i)) as assessed using the fluorescent Ca(2+) indicator, fura-2. The ACTH-induced changes in [Ca(2+)](i) are consistent with MC2-R signaling and consist of both an intracellular release and an extracellular influx of Ca(2+). Both mouse aortic mesenchymal progenitors and mouse macrophage cells express POMC and the prohormone convertase 1/3 (PC1/3) indicating they have the potential to contribute to the local production of POMC peptides. These data demonstrate functional MC2-R expression in mouse aorta-derived mesenchymal progenitors and implicate both macrophage and mesenchymal cells as relevant sources of local POMC peptides. PMID- 22306085 TI - Distinct phosphorylations on kinesin costal-2 mediate differential hedgehog signaling strength. AB - The graded Hedgehog (Hh) signal is transduced by the transmembrane Smoothened (Smo) proteins in both vertebrates and invertebrates. In Drosophila, associations between Smo and the Fused (Fu)/Costal-2 (Cos2)/Cubitus Interruptus (Ci) cytoplasmic complex lead to pathway activation, but it remains unclear how the cytoplasmic complex responds to and transduces different levels of Hh signaling. We show here that, within the Hh gradient field, low- and high-magnitude Smo activations control differentially the phosphorylation of Cos2 on two distinct serines. We also provide evidence that these phosphorylations depend on the Fu kinase activity and lead to a shift of Cos2 distribution from the cytoplasm to the plasma membrane. Moreover, the distinct Cos2 phosphorylation states mediate differential Hh signaling magnitude, suggesting that phosphorylation and relocation of Cos2 to the plasma membrane facilitate high-level Hh signaling through the control of Ci nuclear translocation and transcriptional activity. PMID- 22306086 TI - Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation. AB - Lymphatic valves are essential for efficient lymphatic transport, but the mechanisms of early lymphatic-valve morphogenesis and the role of biomechanical forces are not well understood. We found that the transcription factors PROX1 and FOXC2, highly expressed from the onset of valve formation, mediate segregation of lymphatic-valve-forming cells and cell mechanosensory responses to shear stress in vitro. Mechanistically, PROX1, FOXC2, and flow coordinately control expression of the gap junction protein connexin37 and activation of calcineurin/NFAT signaling. Connexin37 and calcineurin are required for the assembly and delimitation of lymphatic valve territory during development and for its postnatal maintenance. We propose a model in which regionally increased levels/activation states of transcription factors cooperate with mechanotransduction to induce a discrete cell-signaling pattern and morphogenetic event, such as formation of lymphatic valves. Our results also provide molecular insights into the role of endothelial cell identity in the regulation of vascular mechanotransduction. PMID- 22306087 TI - An index approach to performance-based payments for water quality. AB - In this paper we describe elements of a field research project that presented farmers with economic incentives to control nitrate runoff. The approach used is novel in that payments are based on ambient water quality and water quantity produced by a watershed rather than proxies for water quality conservation. Also, payments are made based on water quality relative to a control watershed, and therefore, account for stochastic fluctuations in background nitrate levels. Finally, the program pays farmers as a group to elicit team behavior. We present our approach to modeling that allowed us to estimate prices for water and resulting payment levels. We then compare these preliminary estimates to the actual values recorded over 33 months of fieldwork. We find that our actual payments were 29% less than our preliminary estimates, due in part to the failure of our ecological model to estimate discharge accurately. Despite this shortfall, the program attracted the participation of 53% of the farmers in the watershed, and resulted in substantial nitrate abatement activity. Given this favorable response, we propose that research efforts focus on implementing field trials of group-level performance-based payments. Ideally these programs would be low risk and control for naturally occurring contamination. PMID- 22306088 TI - Event-related potentials reveal early activation of body part representations in action concept comprehension. AB - With tasks involving action concept comprehension, many fMRI studies have reported brain activations in sensori-motor regions specific to effectors of the referent action. There is relatively less evidence whether such activations reflect early semantic access or late conceptual re-processing. Here we recorded event-related potentials when participants recognized noun-verb pairs. For Congruent pairs, the verb was the one most commonly associated with the noun (e.g., football-kick). Compared with a control condition, verbs in Congruent pairs showed priming effects in the time windows of 100-150 ms and 210-260 ms. Such activation seems to be specific to body part but not other aspects of the action as similar priming effect was also found when the noun and verb involved different actions though sharing the same body part (e.g., football-jump), documenting for the first time the early activation of body part representations in action concept comprehension. PMID- 22306089 TI - Age of onset of marijuana use impacts inhibitory processing. AB - Difficulties in the ability to successfully inhibit impulsive behaviors have been reported in marijuana (MJ) smokers, yet few studies have made direct comparisons between early (prior to age 16) and late (age 16 or later) onset MJ smokers, specifically during behavioral inhibition tasks. The current study utilized the Multi-Source Interference Task (MSIT) during functional magnetic resonance imaging (fMRI) in chronic, heavy MJ smokers and healthy non-MJ smoking controls which revealed a more focal pattern of anterior cingulate activity in controls relative to smokers. Early onset smokers had more focal activation but tended to make more errors of commission relative to late onset smokers, suggesting a possible neural adaptation despite difficulty with behavioral inhibition. Further investigation is warranted, as early exposure to MJ may result in reorganization of critical brain regions. PMID- 22306090 TI - Olfactory abnormalities in anxiety disorders. AB - The olfactory system plays an important role in both animal and human anxiety reactions. However, results on olfactory performance during the course of clinical anxiety disorders remain scarce. Therefore, we conducted an exploratory pilot study in 17 patients currently diagnosed with an anxiety disorder. Patients participated in olfactory and psychological testing and were compared to 17 healthy controls. Statistical analyses revealed significant deficits concerning olfactory discrimination in patients, while no changes in threshold and identification ability occurred. Most interestingly, patients showed higher intensity estimates and an increased rating range concerning olfactory hedonic judgements. Results are discussed in light of prior findings and related to neural correlates of olfactory perception and anxiety reactions. PMID- 22306091 TI - Hippocampal neurotransmitter efflux during one-trial novel object recognition in rats. AB - Several lines of evidence point to a role for the hippocampal formation and contiguous temporal lobe structures in a variety of learning and memory paradigms. Presumably, these cognitive phenomena are mediated (and accompanied) by dynamic changes in neurochemical transmission that may differ between learning and recall phases. However, the neurotransmitter correlates of most memory related tasks have not been thoroughly investigated. Here we used a one-trial object recognition paradigm paired with in vivo microdialysis to assess hippocampal acetylcholine (ACh), glutamate and GABA efflux when rats were exposed to familiar objects, and when given the option to explore familiar and novel objects. Rats preferentially explored the novel object over the familiar one when presented with the option. Regardless of object familiarity, object exploration was accompanied by an increase in hippocampal ACh efflux, while GABA efflux was unaffected. However, glutamate efflux was not increased above baseline levels by presentation of familiar objects, but was significantly enhanced in the presence of the novel object. These data suggest that the hippocampus, and in particular, hippocampal glutamate, may be involved in memory processes during novelty recognition paradigms. PMID- 22306092 TI - Cell death starts early after subarachnoid hemorrhage. AB - Brain injury begins early after aneurysmal subarachnoid hemorrhage (SAH). Although cell death via apoptosis and necrosis is known to be present in brain 24 h after SAH, it is not known how soon after SAH cell death begins. We have previously described structural changes in rat brain microvessels 10 min after induction of SAH by endovascular puncture. This study examined brain for evidence of cell death beginning 10 min after induction of SAH. Cleaved caspase-3 (cl caspase-3) staining was evident in vascular and parenchymal cells at 10 min after SAH and was significantly greater than in time-matched, sham-operated controls. The number of cl-caspase-3 positive cells was increased further at 24 h after SAH. TUNEL assay revealed apoptotic cells present at 10 min, with substantially more at 24 h after SAH. Scattered Fluoro-Jade positive neurons appeared at 1h after SAH and their number increased with time. At 1 h Fluoro-Jade positive neurons were present in cortical and subcortical regions but not in hippocampus; at 24h they were also present in hippocampus and were significantly greater in the hemisphere ipsilateral to the vascular puncture. No Fluoro-Jade staining was present in shams. These data demonstrate an early activation of endothelial and parenchymal cells apoptosis and neuronal necrosis after SAH and identifies endpoints that can be targeted to reduce early brain injury after SAH. PMID- 22306093 TI - Melatonin modulates cytoskeletal organization in the rat brain hippocampus. AB - Melatonin concentration in plasma reaches high levels during the night and synchronizes body rhythms with the photoperiod. Previous evidence obtained in cultured cells suggests that melatonin synchronizes cytoskeletal re-arrangements at nocturnal plasma concentration. In this study, we determined the amount of microtubules and microfilaments in the rat hippocampus as an index of cytoskeletal organization in rats submitted to a photoperiodic regime. Additionally, these parameters were determined in control rats, sham rats, pinealectomized rats, and rats that were pinealectomized and treated with melatonin for 1 week. The results showed an increase in both the amount of microfilaments in the hippocampus of rats sacrificed in the dark phase, and in melatonin levels. In addition, a decrease in both microfilament and microtubule amounts occurred in pinealectomized rats. In contrast, melatonin treatment partially reestablished actin and tubulin proportions organized in microfilaments and microtubules, respectively. The results indicate that actin organization in microfilaments was associated with both the photoperiod and with melatonin levels. Together, the data support that cytoskeletal organization is regulated rhythmically by melatonin in synchrony with the photoperiod. PMID- 22306094 TI - Corticotrophin-releasing factor inhibits neuromedin U mRNA expressing neuron in the rat hypothalamic paraventricular nucleus in vitro. AB - In the present study, we examined the effects of corticotrophin-releasing factor (CRF) on neuromedin U (NMU) mRNA-expressing neurons in the rat paraventricular nucleus (PVN) by whole-cell patch-clamp recordings and single-cell reverse transcription-multiplex polymerase chain reaction (single-cell RT-mPCR) techniques. In total, of 116 PVN putative parvocellular neurons screened for NMU mRNA, 14.7% (17/116) of them expressed NMU mRNA. The electrophysiological properties observed in the NMU mRNA-expressing neurons were generation of a low threshold Ca(2+) spike (LTS) and robust low voltage-activated (T-type) Ca(2+) currents. Under current-clamp conditions, CRF (100 nM) induced a reversible decrease in spike firing and significantly diminished the LTS in 88.2% (15/17) of NMU mRNA-expressing neurons. Extracellular application of 1 MUM alpha-helical CRF (9-14) (alpha-hCRF), a selective CRF receptor antagonist, completely blocked the CRF-induced decrease in spike firing in the NMU mRNA-expressing neurons. Under voltage-clamp conditions, CRF (100 nM) significantly decreased the peak value of the T-type Ca(2+) currents by 35.6+/-7.8%. These findings suggest that CRF decreases neuronal excitability and diminishes T-type Ca(2+) currents in a population of rat PVN NMU phenotype neurons in vitro. PMID- 22306095 TI - Selective serotonin receptor stimulation of the medial nucleus accumbens differentially affects appetitive motivation for food on a progressive ratio schedule of reinforcement. AB - Previously, we reported that stimulation of selective serotonin (5-HT) receptor subtypes in the nucleus accumbens shell differentially affected consumption of freely available food. Specifically, activation of 5-HT(6) receptors caused a dose-dependent increase in food intake, while the stimulation of 5-HT(1/7) receptor subtypes decreased feeding [34]. The current experiments tested whether similar pharmacological activation of nucleus accumbens serotonin receptors would also affect appetitive motivation, as measured by the amount of effort non deprived rats exerted to earn sugar reinforcement. Rats were trained to lever press for sugar pellets on a progressive ratio 2 schedule of reinforcement. Across multiple treatment days, three separate groups (N=8-10) received bilateral infusions of the 5-HT(6) agonist EMD 386088 (at 0.0, 1.0 and 4.0 MUg/0.5 MUl/side), the 5-HT(1/7) agonist 5-CT (at 0, 0.5, 1.0, or 4.0 MUg/0.5 MUl/side), or the 5-HT(2C) agonist RO 60-0175 fumarate (at 0, 2.0, or 5.0 MUg/0.5 MUl/side) into the anterior medial nucleus accumbens prior to a 1-h progressive ratio session. Stimulation of 5-HT(6) receptors caused a dose-dependent increase in motivation as assessed by break point, reinforcers earned, and total active lever presses. Stimulation of 5-HT(1/7) receptors increased lever pressing at the 0.5 MUg dose of 5-CT, but inhibited lever presses and break point at 4.0 MUg/side. Injection of the 5-HT(2C) agonist had no effect on motivation within the task. Collectively, these experiments suggest that, in addition to their role in modulating food consumption, nucleus accumbens 5-HT(6) and 5-HT(1/7) receptors also differentially regulate the appetitive components of food-directed motivation. PMID- 22306096 TI - Involvement of PKCalpha-MAPK/ERK-phospholipase A(2) pathway in the Escherichia coli invasion of brain microvascular endothelial cells. AB - Escherichia coli K1 is the most common Gram-negative organism that causes neonatal meningitis following penetration of the blood-brain barrier. In the present study we demonstrated the involvement of cytosolic (cPLA(2)) and calcium independent phospholipase A(2) (iPLA(2)) and the contribution of cyclooxygenase-2 products in E. coli invasion of microvascular endothelial cells. The traversal of bacteria did not determine trans-endothelial electrical resistance (TEER) and ZO 1 expression changes and was reduced by PLA(2)s siRNA. cPLA(2) and iPLA(2) enzyme activities and cPLA(2) phosphorylation were stimulated after E. coli incubation and were attenuated by PLA(2), PI3-K, ERK 1/2 inhibitors. Our results demonstrate the role of PKCalpha/ERK/MAPK signaling pathways in governing the E. coli penetration into the brain. PMID- 22306097 TI - [Atypical polypoid adenomyoma: retrospective study about 8 cases from Jeanne-de Flandre Hospital between 1996 and 2008]. AB - OBJECTIVES: To propose a therapeutic approach and follow-up of patients with atypical polypoid adenomyoma (APA) wishing to remain fertile. PATIENTS AND METHOD: We are presenting a retrospective study of eight APA cases. RESULTS: Two patients immediately received radical treatment, and one patient had an endometrial thermocoagulation. The remaining five patients received a conservative treatment with ultrasound and hysteroscopic monitoring. Among them, two had full-term pregnancies, one is being treated for infertility, in one case, the APA disappeared after three hysteroscopy-curettages and macroprogestative treatment. Lastly, one of our patients died from an aggressive endometrioid ovarian bilateral tumour associated with an endometrial adenocarcinoma. DISCUSSION AND CONCLUSION: Radical treatment is necessary for cases of APA in women no longer wishing to remain fertile. For those wishing to remain fertile, we can offer a conservative treatment once they have been informed regarding the associated risk of relapse, degeneration, and ovarian lesions which necessitate stricter follow-up. PMID- 22306098 TI - Mycotic abdominal aortic aneurysm caused by toxigenic Clostridium difficile. AB - Extra-intestinal infections caused by Clostridium difficile are uncommon. We report a case of a mycotic abdominal aortic aneurysm in an 86-year old male. Tissue and pus swabs from the aneurysmal sac grew a pure growth of C. difficile. The identity of the isolate was determined by phenotypic methods and confirmed by DNA sequencing. He was treated successfully with an aorta-bifemoral bypass and a 4-week course of intravenous and oral antibiotics. PMID- 22306099 TI - Association between the functional polymorphism (C3435T) of the gene encoding P glycoprotein (ABCB1) and major depressive disorder in the Japanese population. AB - Human P-glycoprotein (P-gp), which is encoded by ABCB1 (ATP-binding cassette, sub family B member 1), is expressed in the blood brain barrier and protects the brain from many kinds of drugs and toxins including glucocorticoids by acting as an efflux pump. We examined whether functional polymorphisms of ABCB1 give susceptibility to major depressive disorder (MDD). The five functional single nucleotide polymorphisms (SNPs), A-41G (rs2188524), T-129C (rs3213619), C1236T (Gly412Gly: rs1128503), G2677A/T (Ala893Ser/Thr: rs2032582), and C3435T (Ile1145Ile: rs1045642) were genotyped in 631 MDD patients and 1100 controls in the Japanese population. A tri-allelic SNP, G2677A/T, was genotyped by pyrosequencing and the remaining SNPs were genotyped by the TaqMan 5'-exonuclease allelic discrimination assay. The minor T3435 allele was significantly increased in MDD patients than in the controls (chi(2) = 4.5, df = 1, p = 0.034, odds ratio [OR] 1.16, 95% confidential interval [CI] 1.01-1.34). Homozygotes for the T3435 allele was significantly more common in patients than in the controls (chi(2) = 7.5, df = 1, p = 0.0062, OR 1.43, 95%CI 1.11-1.85). With respect to the other 4 SNPs, there was no significant difference in genotype or allele distribution. In the haplotype-based analysis, the proportion of individuals with the TT1236 TT3435 haploid genotype was significantly increased in patients than in controls (chi(2) = 8.5, df = 1, p = 0.0037, OR 1.50, 95%CI 1.14-1.98). Our results suggest that the T3435 allele or carrying two copies of this allele confers susceptibility to MDD in the Japanese population. PMID- 22306100 TI - High-degree right bundle branch block obscuring the diagnosis of Brugada electrocardiographic pattern. PMID- 22306101 TI - Impairment of trafficking by downregulation of an anchor protein: novel insights into additional mechanisms responsible for heart failure. PMID- 22306102 TI - Emerging approaches of traditional Chinese medicine formulas for the treatment of hyperlipidemia. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) formulas have been widely used in China since ancient times to treat certain diseases (e.g., phlegm, dampness and blood stasis). Recently, the effects of these medicines have been increasingly demonstrated to be helpful for hyperlipidemic patients. AIM OF THE STUDY: This manuscript aims to describe the scientific evidence for the efficacy of TCM and attempts to identify potential TCM formulas for treating hyperlipidemia. MATERIALS AND METHODS: TCM formulas approved by the State Food and Drug Administration of China (SFDA) were sourced from the official SFDA website (http://www.sda.gov.cn/). Human and animal evidence for the hypolipidemic effects of herbs from TCM formulas were reviewed via the Internet (Elsevier, ACS, Wiley Online Library, SpringerLink, PubMed, Web of Science, CNKI, Baidu, and Google) and libraries up to October 31, 2011. RESULTS: More than 50 TCM formulas have been used to treat hyperlipidemia. These herbs can primarily be grouped into three categories: (1) herbs promoting excretions, generally by reducing food retention, enhancing purgative effects, and promoting diuresis and choleretic effects, e.g., Fructus Crataegi (), Radix Polygoni Multiflori (), Semen Cassiae (), and Radix et Rhizoma Rhei (), Rhizoma alismatis (), and Herba Artemisiae Scopariae (); (2) herbs acting on the cardiovascular system, generally by improving blood circulation based on TCM theories, e.g., Radix Salviae Miltiorrhizae (), Radix Puerariae (), Rhizoma Chuanxiong (), Flos Carthami (), and Folium Nelumbinis (); and (3) herbs that have tonic effects, e.g., Fructus Lycii (), Radix Ginseng (), and Radix Astragali (). CONCLUSIONS: Three basic approaches, including excretory function enhancement, cardiovascular system improvement, and tonic effect reinforcement, are emerging among TCM formulas for the treatment of hyperlipidemia. These approaches may be useful in controlling blood lipid levels, preventing cardiovascular complications, and adjusting bodily functions in hyperlipidemic patients. However, solid evidence of the efficacy of these treatments is required. PMID- 22306103 TI - Residual infrarenal aortic neck following endovascular and open aneurysm repair. AB - BACKGROUND: The effectiveness of open and endovascular aneurysm repair of aortic abdominal aneurysms (AAAs) can be jeopardised by deterioration of the residual infrarenal neck of the aneurysm. OBJECTIVE: The study aims to determine the length of the residual infrarenal aortic segment after endovascular and open aneurysm repair. METHODS: In a multicentre randomised controlled trial comparing open and endovascular AAA repair, 165 patients were discharged after open AAA repair (OR) and 169 after endovascular repair (EVAR). Immediately after the operation, surgeons were asked to enter in the case record form whether the level of their anastomosis after open repair was within or beyond 10 mm of the caudal renal artery. Postoperative computed tomography (CT) scans that were obtained within 6 months after surgery were used for comparative analysis. The distance between the caudal renal artery and the proximal anastomosis of the (endo-) graft was measured using axial CT slices and a standardised protocol. CT images were available and suitable for analysis in 156 (95%) of 165 OR patients and in 160 (95%) of 169 EVAR patients. Data are presented as median (range). Differences were analysed using the Mann-Whitney test. RESULTS: The distance from the caudal renal artery to the proximal anastomosis was 24 mm (16-30 mm) in the OR group versus 0 mm (0-6 mm) in the EVAR group (p < 0.0001, Mann-Whitney). In 140 of 156 (90%) patients, at least 1 cm of untreated infrarenal neck persisted after OR and in 17 of 160 (10%) after EVAR. In 84 of the 156 open repair patients (54%), the surgeon had indicated that the proximal anastomosis was within 10 mm of the caudal renal artery. Only five surgeons (6%) were accurate in this respect. CONCLUSION: After open repair, a longer segment of the infrarenal aortic neck is left untreated compared with endovascular repair and this length is underestimated by most surgeons. Long-term studies are required to determine the consequences of this difference. PMID- 22306104 TI - Evaluation of three different formats of a neutralizing single chain human antibody against toxin Cn2: neutralization capacity versus thermodynamic stability. AB - The single-chain antibody fragment (scFv) 6009F, obtained by directed evolution, neutralizes the effects of the Cn2 toxin, which is the major toxic component of Centruroides noxius scorpion venom. In this work we compared the neutralization capacity and the thermodynamic stability of scFv 6009F with those of two other derived formats: Fab 6009F and diabody 6009F. Additionally, the affinity constants to Cn2 toxin of the three recombinant antibody fragments were determined by means of BIAcore. We found a correlation between the thermodynamic stability of these antibody fragments with their neutralization capacity. The order of thermodynamic stability determined was Fab?scFv>diabody. The Fab and scFv were capable of neutralizing the toxic effects of Cn2 and whole venom but the diabody was unable to fully neutralize intoxication. In silico analysis of the diabody format indicates that the reduction of stability and neutralization capacity could be explained by a less cooperative interface between the heavy and the light variable domains. PMID- 22306105 TI - Complementing antibody profiles: assessing antibody function on antigen microarrays. AB - Antibody effector functions other than neutralization depend on interactions with soluble and cellular components of the immune system. Antigen recognition is usually oligoclonal, with the different clones of antibodies belonging to different classes, subclasses, glycoforms and having different affinities and epitope specificities. Thus, composition of immune complexes determines biological effects mainly via interactions with FcR and complement proteins. Antibodies are capable of triggering any of the three pathways of complement activation and antigen recognition of complex antigens often results in the activation of more than one pathway. These events can be tracked in a multiplex format using antigen microarrays, where complement products bind to elements of the microarray. By controlling cation concentrations and detecting various complement components (C1q, C4, C3) contribution of the different pathways can be identified. Parallel measurement of antibodies and complement proteins provides a novel way of looking at interactions between antigen and antibodies. We propose the use of immune complex signatures, composite depictions of antibody and complement content of immune complexes characterizing healthy and diseased populations. Normalized interquartile ranges of antibody binding (IgM, IgG) and complement deposition (C4, C3) are projected onto radar charts to produce patterns that can distinguish normal and altered immune responses. We propose that comprehensive interaction studies of serum antibodies and complement with arrays of antigens can generate functional antibody profiles and help better understand immunological disease mechanism. PMID- 22306106 TI - TAT-mediated oral subunit vaccine against white spot syndrome virus in crayfish. AB - White spot syndrome virus is a highly pathogenic virus that infects crayfish and other crustaceans. VP28 is one of its major envelope proteins, and plays a crucial role in viral infection. Cell-penetrating peptides are short peptides that facilitate cellular uptake of various molecular cargoes, and one well known example is TAT peptide from HIV-1 TAT protein. In this study, recombinant plasmids were constructed and transformed into Escherichia coli strain BL21 (DE3) to express TAT-VP28, VP28, TAT-VP28-EGFP and VP28-EGFP fusion proteins. Enzyme linked immunosorbent assay (ELISA) and flow cytometry methods were used to confirm that TAT fusion proteins can translocate from the intestine to the hemolymph of the crayfish Cambarus clarkii. After immunization, activities of phenoloxidase and superoxide dismutase were analyzed, and it was found that rTAT VP28 produced the most pronounced increase in both C. clarkii were vaccinated by oral administration of rTAT-VP28 and rVP28 for 7 and 14 days, and rTAT-VP28 resulted in the highest relative percent survival (RPS) (63.3% at 7 days, and 67.8% at 14 days), compared with rVP28 (44.4% at 7 days, and 53.6% at 14 days) following challenge with WSSV after the last day of feeding. This study reports the use of TAT-derived peptide as an oral delivery method of a subunit vaccine against WSSV in C. clarkii. PMID- 22306107 TI - Comparison of methods for the detection of coliphages in recreational water at two California, United States beaches. AB - Methods for detection of two fecal indicator viruses, F+ and somatic coliphages, were evaluated for application to recreational marine water. Marine water samples were collected during the summer of 2007 in Southern California, United States from transects along Avalon Beach (n=186 samples) and Doheny Beach (n=101 samples). Coliphage detection methods included EPA method 1601 - two-step enrichment (ENR), EPA method 1602 - single agar layer (SAL), and variations of ENR. Variations included comparison of two incubation times (overnight and 5-h incubation) and two final detection steps (lysis zone assay and a rapid latex agglutination assay). A greater number of samples were positive for somatic and F+ coliphages by ENR than by SAL (p<0.01). The standard ENR with overnight incubation and detection by lysis zone assay was the most sensitive method for the detection of F+ and somatic coliphages from marine water, although the method takes up to three days to obtain results. A rapid 5-h enrichment version of ENR also performed well, with more positive samples than SAL, and could be performed in roughly 24h. Latex agglutination-based detection methods require the least amount of time to perform, although the sensitivity was less than lysis zone based detection methods. Rapid culture-based enrichment of coliphages in marine water may be possible by further optimizing culture-based methods for saline water conditions to generate higher viral titers than currently available, as well as increasing the sensitivity of latex agglutination detection methods. PMID- 22306108 TI - Immobilization of Burkholderia sp. lipase on a ferric silica nanocomposite for biodiesel production. AB - In this work, lipase produced from an isolated strain Burkholderia sp. C20 was immobilized on magnetic nanoparticles to catalyze biodiesel synthesis. Core-shell nanoparticles were synthesized by coating Fe(3)O(4) core with silica shell. The nanoparticles treated with dimethyl octadecyl [3-(trimethoxysilyl) propyl] ammonium chloride were used as immobilization supporters. The Burkholderia lipase was then bound to the synthesized nanoparticles for immobilization. The protein binding efficiency on alkyl-functionalized Fe(3)O(4)-SiO(2) was estimated as 97%, while the efficiency was only 76% on non-modified Fe(3)O(4)-SiO(2). Maximum adsorption capacity of lipase on alkyl-functionalized Fe(3)O(4)-SiO(2) was estimated as 29.45 mg g(-1) based on Langmuir isotherm. The hydrolytic kinetics (using olive oil as substrate) of the lipase immobilized on alkyl-grafted Fe(3)O(4)-SiO(2) followed Michaelis-Menten model with a maximum reaction rate and a Michaelis constant of 6251 Ug(-1) and 3.65 mM, respectively. Physical and chemical properties of the nanoparticles and the immobilized lipase were characterized by Brunauer-Emmett-Teller (BET) analysis, scanning electron microscope (SEM), and Fourier transform infrared spectroscopy (FT-IR). Moreover, the immobilized lipase was used to catalyze the transesterification of olive oil with methanol to produce fatty acid methyl esters (FAMEs), attaining a FAMEs conversion of over 90% within 30 h in batch operation when 11 wt% immobilized lipase was employed. The immobilized lipase could be used for ten cycles without significant loss in its transesterification activity. PMID- 22306109 TI - Organosoluble enzyme conjugates with poly(2-oxazoline)s via pyromellitic acid dianhydride. AB - The use of enzymes in organic solvents offers a great opportunity for the synthesis of complex organic compounds and is therefore in focus of current research. In this work we describe the synthesis of poly(2-methyl-1,3-oxazoline) (PMOx) and poly(2-ethyl-1,3-oxazoline) (PEtOx) enzyme conjugates with hen-egg white lysozyme, RNase A and alpha-chymotrypsin using a new coupling technique. The POXylation was carried out reacting pyromellitic acid dianhydride subsequently with ethylenediamine terminated POx and then with the NH2-groups of the respective enzymes. Upon conjugation with the polymers, RNase A and lysozyme became fully soluble in DMF (1.4 mg/ml). These are the first examples of fully POXylated proteins, which become organosoluble. The synthesized enzyme conjugates were characterized by SDS-PAGE, isoelectric focusing, dynamic light scattering and size exclusion chromatography, which all indicated the full POXylation of the enzymes. The modified enzymes even partly retained their activity in water. With alpha-chymotrypsin as example we could demonstrate that the molecular weight of the attached polymer significantly influences the activity. PMID- 22306110 TI - The effects of ROS-mediating oxygen tension on human CD34(+)CD38(-) cells induced into mature dendritic cells. AB - Oxygen tension regulates the biological characteristics of hematopoietic stem and progenitor cells (HSPCs) by modulating intracellular reactive oxygen species (ROS). To better understand oxygen tension mechanism on HSPCs culture, gene expression analysis of human CD34(+)CD38(-) HSPCs was performed using microarrays. The CD34(+)CD38(-) HSPCs cultured under normoxia, hypoxia, or with N acetyl cysteine (NAC, an ROS scavenger) were isolated for transcriptional profilings. Compared to normoxia group, 1 gene was up-regulated and 22 genes were down-regulated in hypoxia group, while 1 gene was up-regulated and 29 genes were down-regulated in NAC group. These differently expressed genes were involved in cell surface markers, blood activation and differentiation. The common down regulated genes related to dendritic cells (DCs) maturation (CD80, CD86, and JAG1) were confirmed by real-time RT-PCR. Furthermore, the analysis of the phenotypes of DCs, including the DC-characteristic surface molecule CD1a, the costimulatory molecules CD80 and CD86, and HLA-DR, associated with the capacity of DCs to stimulate allogeneic T cells, showed that hypoxia-mediating ROS inhibited the potential of CD34(+)CD38(-) HSPCs differentiating to mature DCs. All these results demonstrated that hypoxia-reducing ROS down-regulated the genes driving CD34(+)CD38(-) HSPCs differentiation, which provides an interesting molecular hint to direct their development to DCs during cultures. PMID- 22306111 TI - Computational identification of microRNA gene loci and precursor microRNA sequences in CHO cell lines. AB - MicroRNAs (miRNAs) have recently entered Chinese hamster ovary (CHO) cell culture technology, due to their severe impact on the regulation of cellular phenotypes. Applications of miRNAs that are envisioned range from biomarkers of favorable phenotypes to cell engineering targets. These applications, however, require a profound knowledge of miRNA sequences and their genomic organization, which exceeds the currently available information of ~400 conserved mature CHO miRNA sequences. Based on these recently published sequences and two independent CHO-K1 genome assemblies, this publication describes the computational identification of CHO miRNA genomic loci. Using BLAST alignment, 415 previously reported CHO miRNAs were mapped to the reference genomes, and subsequently assigned to a distinct genomic miRNA locus. Sequences of the respective precursor-miRNAs were extracted from both reference genomes, folded in silico to verify correct structures and cross-compared. In the end, 212 genomic loci and pre-miRNA sequences representing 319 expressed mature miRNAs (approximately 50% of miRNAs represented matching pairs of 5' and 3' miRNAs) were submitted to the miRBase miRNA repository. As a proof-of-principle for the usability of the published genomic loci, four likely polycistronic miRNA cluster were chosen for PCR amplification using CHO-K1 and DHFR (-) genomic DNA. Overall, these data on the genomic context of miRNA expression in CHO will simplify the development of tools employing stable overexpression or deletion of miRNAs, allow the identification of miRNA promoters and improve detection methods such as microarrays. PMID- 22306112 TI - Differential expression of silent polyketide biosynthesis gene clusters in chemostat cultures of Aspergillus nidulans. AB - The genome of the fungal model organism Aspergillus nidulans harbors nearly 30 polyketide synthase genes, yet the majority of these genes remain silent in the absence of particular stimuli. In this study, environmental conditions such as low specific microbial growth rate as well as nitrate, orthophosphate and glucose limitations were simulated under a continuous cultivation regime to induce the expression of silent polyketide synthase genes. In addition to offline and online bioprocess parameters, the physiological equilibrium was defined at the transcript level in terms of indicator gene expression. The different cultivation parameters resulted in a differential expression of two polyketide synthase genes coding for the biosynthesis of a variety of phenolic compounds, such as orsellinic acid, lecanoric acid, emodins, chrysophanol, shamixanthone, and sanghaspirodin. Further investigation of the metabolome revealed the formation of a novel prenylated benzophenone derivative designated as pre-shamixanthone. Our data indicate that employing chemostat fermentations in combination with genome mining, transcriptome analysis and metabolic profiling represents a valuable approach for triggering cryptic biosynthetic pathways. PMID- 22306113 TI - Moving toward multimedia electronic health records: how do we get there? AB - This report, based on a workshop jointly sponsored the National Institute of Biomedical Imaging and Biomedical Engineering and the Office of the National Coordinator for Health Information Technology, examines the role and value of images as multimedia data in electronic health records (EHRs). The workshop, attended by a wide range of stakeholders, was motivated in part by the absence of image data from discussions of meaningful use of health information technology. Collectively, the workshop presenters and participants argued that images are not ancillary data and should be central to health information systems to facilitate clinical decisions and higher quality, efficiency, and safety of care. They emphasized that the imaging community has already developed standards that form the basis of interoperability. Despite the apparent value of images, workshop participants also identified challenges and barriers to their implementation within EHRs. Weighing the opportunities and challenges, workshop participants provided their perspectives on possible paths forward toward fully multimedia EHRs. PMID- 22306115 TI - Prostate cancer risk prediction in a urology clinic in Mexico. AB - OBJECTIVES: To evaluate factors affecting the risk of prostate cancer (CaP) and high-grade disease (HGCaP, Gleason score >= 7) in a Mexican referral population, with comparison to the Prostate Cancer Prevention Trial Prostate Cancer Risk Calculator (PCPTRC). METHODS AND MATERIALS: From a retrospective study of 826 patients who underwent prostate biopsy between January 2005 and December 2009 at the Instituto Nacional de Cancerologia, Mexico, logistic regression was used to assess the effects of age, prostate-specific antigen (PSA), digital rectal exam (DRE), first-degree family history of CaP, and history of a prior prostate biopsy on CaP and HGCaP, separately. Internal discrimination, goodness-of-fit, and clinical utility of the resulting models were assessed with comparison to the PCPTRC. RESULTS: Rates of both CaP (73.2%) and HGCaP (33.3%) were high among referral patients in this Mexican urology clinic. The PCPTRC generally underestimated the risk of CaP but overestimated the risk of HGCaP. Four factors influencing CaP on biopsy were logPSA, DRE, family history and a prior biopsy history (all P < 0.001). The internal AUC of the logistic model was 0.823 compared with 0.785 of the PCPTRC for CaP (P < 0.001). The same 4 factors were significantly associated with HGCaP as well and the AUC was 0.779 compared with 0.766 of the PCPTRC for HGCaP (P = 0.13). CONCLUSIONS: Lack of screening programs or regular urologic checkups in Mexico imply that men typically first reach specialized clinics with a high cancer risk. This renders diagnostic tools developed on comparatively healthy populations, such as the PCPTRC, of lesser utility. Continued efforts are needed to develop and externally validate new clinical diagnostic tools specific to high-risk referral populations incorporating new biomarkers and more clinical characteristics. PMID- 22306116 TI - Three unusual factors contributing to compressive median neuropathy in the distal forearm in a single patient. AB - Although there are varied aetiological factors responsible for compressive neuropathy of the median nerve in the carpal tunnel syndrome, it is rare to encounter several aetiological factors in a single case. This article reports a case in which three aetiological factors were present. PMID- 22306117 TI - Mapping key interactions in the dimerization process of HBHA from Mycobacterium tuberculosis, insights into bacterial agglutination. AB - HBHA is a cell-surface protein implicated in the dissemination of Mycobacterium tuberculosis (Mtb) from the site of primary infection. Its N-terminal coiled-coil region is also involved in bacterial agglutination. However, despite the importance of HBHA dimerization in agglutination, protein regions involved in dimerization are hitherto not known. Here, we mapped these regions by coupling peptide synthesis, biochemical and computational analyses, and identified structural determinants for HBHA monomer-monomer recognition. Importantly, we obtained the first molecule able to induce HBHA dimer disaggregation at 37 degrees C, the typical growth temperature of Mtb. This result provides new opportunities towards the development of Mtb anti-aggregation molecules with therapeutic interest. PMID- 22306118 TI - Use of Kikume green-red fusions to study the influence of pharmacological chaperones on trafficking of G protein-coupled receptors. AB - In this study we demonstrate that the photoconvertible monomeric Kikume green-red (mKikGR) protein is suitable to study trafficking of G protein-coupled receptors. Taking mKikGR-tagged mutants of the vasopressin V(2) receptor (V(2)R) as models, we analyzed whether the V(2)R-specific pharmacological chaperone SR121463B influences receptor folding on a co- or post-translational level. Misfolded mKikGR-tagged V(2)Rs were completely photoconverted in the early secretory pathway yielding a red receptor population (already synthesized receptors) and an arising green receptor population (newly synthesized receptors). Trafficking of both receptor populations could be rescued by treatment with SR121463B demonstrating that the substance can act co- and post-translationally. PMID- 22306119 TI - Adaptive diversity of innate immune receptor family short pentraxins in Murinae. AB - The short pentraxins C-reactive protein (CRP) and serum amyloid P component (SAP) constitute a group of innate immune receptors that trigger immune activation by detecting molecules of the microbial cell wall. Here, we examined the evolution of short pentraxins in Murinae lineages. By molecular evolutionary analysis, CRP and SAP have been experiencing rapid diversification, driven by adaptive selection. Further, our protein modeling demonstrates that adaptively selected amino acids lie in the ligand-binding region and contact region between subunits. Our findings suggest that rapid diversification of these regions could contribute to the determinants of recognizing specificity and the interaction between subunits. PMID- 22306120 TI - Genetic polymorphisms in DNA repair genes OGG1, APE1, XRCC1, and XPD and the risk of age-related cataract. AB - PURPOSE: To analyze the association of the polymorphisms in 8-oxoguanine glycosylase-1 (OGG1), X-ray repair cross-complementing-1 (XRCC1), and AP endonuclease-1 (APE1) genes in the base excision repair pathway and xeroderma pigmentosum complementation group D (XPD) in the nucleotide excision repair pathway with the risk of cataract in a Chinese population. DESIGN: Case-control study. PARTICIPANTS: Subjects with cataract (n = 415) or no cataract (n = 386) in the Age Related Eye Disease Ancillary Study. METHODS: The study included 415 cataract patients and 386 controls. Genotyping was carried out by the polymerase chain reaction-restriction fragment length polymorphism method. Differences in the frequencies were estimated by the chi-square test, and risk was estimated by using unconditional logistic regression after adjusting for age and gender. MAIN OUTCOME MEASURES: Association of single nucleotide polymorphisms in OGG1 Ser326Cys with the development of age-related cataract. RESULTS: The OGG1 Cys/Cys genotype frequency was significantly higher in cataract patients (P = 0.014; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.171-3.624). The OGG1 Ser/Ser genotype (P = 0.003; OR, 0.647; 95% CI, 0.487-0.860) seems to have a protective role against cataract, and the Cys allele (P<0.001; OR, 1.517; 95% CI, 1.204 1.911) seems to have a deleterious role in the development of cataract. The genotype frequency of the Ser/Ser of OGG1-Ser326Cys was significantly different in the cortical and mixed-type cataract group (P = 0.014; OR, 0.591; 95% CI, 0.391-0.893; and P = 0.035; OR, 0.639; 95% CI, 0.425-0.960; respectively), and the Cys/Cys genotype of OGG1-Ser326Cys was significantly different in the mixed type cataract group (P = 0.012; OR, 2.610; 95% CI, 1.284-5.306) compared with that of healthy controls. In XRCC1-Arg399Gln, APE1-Asp148Glu, and XPD-Lys751Gln polymorphisms, there were no significant differences in frequencies of the variant homozygous in patients compared with controls. CONCLUSIONS: Results suggest that the Cys/Cys genotype of the OGG1-Ser326Cys polymorphism may be associated with increased risk of age-related cataract. However, in XRCC1 Arg399Gln, APE1-Asp148Glu, and XPD-Lys751Gln polymorphisms, there were no significant differences in frequencies of the variant homozygous in patients compared with controls. PMID- 22306121 TI - HORIZON: an open-label extension trial of ranibizumab for choroidal neovascularization secondary to age-related macular degeneration. AB - OBJECTIVE: To evaluate the long-term safety and efficacy of multiple intravitreal ranibizumab injections (Lucentis, Genentech, Inc., South San Francisco, CA) administered at the investigator's discretion in patients with choroidal neovascularization secondary to age-related macular degeneration. DESIGN: An open label, multicenter, extension study. PARTICIPANTS: Patients who completed the controlled treatment phase of 1 of 3 prospective, randomized, 2-year clinical trials of ranibizumab were eligible for enrollment. Analyses were performed for 3 groups: (1) patients treated with ranibizumab in the initial study (ranibizumab treated-initial; n = 600); (2) patients randomized to control who crossed over to receive ranibizumab (ranibizumab treated-XO; n = 190); and (3) ranibizumab-naive patients (ranibizumab untreated; n = 63). METHODS: Ranibizumab 0.5 mg was administered at the investigator's discretion. Adverse events (AEs) and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) assessments were conducted at study visits every 3 to 6 months. MAIN OUTCOME MEASURES: Incidence and severity of AEs. RESULTS: There was 1 occurrence of mild endophthalmitis per 3552 HORIZON injections in the ranibizumab treated initial/ranibizumab treated-XO groups. There were no serious AE reports of lens damage, retinal tears, or rhegmatogenous retinal detachments in the study eyes. The proportion of patients with any single postdose intraocular pressure >=30 mmHg was 9.2%, 6.6%, and 0%, and the proportion of patients with glaucoma was 3.2%, 4.2%, and 3.2% in the ranibizumab treated-initial, ranibizumab treated-XO, and ranibizumab untreated groups, respectively. Cataract AEs were less frequent in the ranibizumab untreated group: 6.3% versus 12.5% and 12.1% in the ranibizumab treated-initial and ranibizumab treated-XO groups, respectively. The proportion of patients with arterial thromboembolic events as defined by the Antiplatelet Trialists' Collaboration was 5.3% in the ranibizumab treated-initial and ranibizumab treated-XO groups, and 3.2% in the ranibizumab untreated group. At month 48 (2 years of HORIZON), the mean change in BCVA (ETDRS letters) relative to the initial study baseline was 2.0 in the ranibizumab treated-initial group versus -11.8 in the pooled ranibizumab treated-XO and ranibizumab untreated groups. CONCLUSIONS: Multiple ranibizumab injections were well tolerated for >=4 years. With less frequent follow-up leading to less treatment, there was an incremental decline of the visual acuity (VA) gains achieved with monthly treatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 22306122 TI - The discovery of aminopyrazines as novel, potent Na(v)1.7 antagonists: hit-to lead identification and SAR. AB - Herein the discovery of a novel class of aminoheterocyclic Na(v)1.7 antagonists is reported. Hit compound 1 was potent but suffered from poor pharmacokinetics and selectivity. The compact structure of 1 offered a modular synthetic strategy towards a broad structure-activity relationship analysis. This analysis led to the identification of aminopyrazine 41, which had vastly improved hERG selectivity and pharmacokinetic properties. PMID- 22306123 TI - Synthesis and biological evaluation of novel amprenavir-based P1-substituted bi aryl derivatives as ultra-potent HIV-1 protease inhibitors. AB - A series of P1-substituted biaryl amprenavir derivatives was designed and synthesized. These compounds were evaluated for enzyme inhibition and antiviral activity in vitro. Several compounds showed highly efficient antiviral activity with EC(50) values down to 0.10nM, which are more potent than marketed HIV-1 protease inhibitors. Docking study indicated that 12c has similar binding mode to amprenavir with full occupancy in P1. PMID- 22306124 TI - Novel bisbenzimide-nitroxides for nuclear redox imaging in living cells. AB - Nuclear oxidative stress damages genomic DNA and may lead to cell death, leading to aging and aging-related disorders. Though it is important to measure the nuclear oxidative stress separately, there are still little examples that applicable to living cells. We have designed and synthesized three bisbenzimide nitroxides as probes to selectively visualize nuclear redox changes in terms of fluorescence. Compound 3, containing two radical moieties, showed the largest reduction-induced fluorescence change, with good localization in nuclei. RAW264.7 murine macrophage cells were loaded with compound 3 and then treated with 100MUM hydrogen peroxide for 5min to show the fluorescence increase. This fluorescence increase was inhibited by pretreatment of 1mM ascorbic acid. These results show that compound 3 was suitable for nuclear-specific redox imaging in murine macrophages. PMID- 22306125 TI - Association between class III beta-tubulin expression and response to paclitaxel/vinorebine-based chemotherapy for non-small cell lung cancer: a meta analysis. AB - BACKGROUND: It has been proposed that the level of class III beta-tubulin gene expression can be used to predict clinical sensitivity to paclitaxel/vinorebine based chemotherapy in non-small cell lung cancer (NSCLC) patients. However, whereas there are published reports supporting this association, there are also reports of studies that failed to find such an association. We conducted a meta analysis of all relevant published data to provide a combined statistical assessment of the proposed association of expression variations of class III beta tubulin with objective response and median survival in patients with NSCLC treated with paclitaxel/vinorebine-based chemotherapy. METHODS: We conducted the meta-analysis using data from ten studies, each of which evaluated the correlation between class III beta-tubulin expression levels and objective response in patients treated with paclitaxel/vinorebine-based chemotherapy for NSCLC patients. All eligible studies were searched by MEDLINE, EMBASE and CNKI databases. Overall odds ratios (ORs) of the objective response were calculated using the method of Mantel-Haenszel. The differences in objective responses between Caucasian and Asian patients treated with paclitaxel/vinorebine-based chemotherapy were compared. We also compared outcomes for patients treated with paclitaxel to those treated with vinorebine. RESULTS: There were a total of 552 patients in the ten studies that met our criteria for evaluation. High/positive expression of class III beta-tubulin was found in 279 patients (50.5%), and low/negative expression for this gene was found in 273 (49.5%) patients. The objective response rate for paclitaxel/vinorebine-based chemotherapy was significantly higher in patients with low/negative class III beta-tubulin expression (OR=0.28; 95% CI, 0.20-0.41; P<0.00001). Median survival time was longer for patients with low/negative expression of class III beta-tubulin compared with patients with high/positive expression (MR=1.40; CI, 0.89-0.90; P<0.00001). There was no significant difference in therapy between Caucasian and Asian patients treated with paclitaxel/vinorebine-based chemotherapy (Chi(2)=0.02, P=0.88). In our analysis, NSCLC patients treated with paclitaxel had more favorable clinical outcomes than those treated with vinorelbine (Chi(2)=3.69, P=0.05). CONCLUSIONS: By combining data from ten different studies, we found a correlation between low TUBB3 gene expression and favorable clinical outcome to anti-tubulin therapy. The correlation for the combined data was significantly stronger than it was for any of the individual studies. This result supports the usefulness of class III beta-tubulin mRNA level as a biomarker for sensitivity to paclitaxel/vinorebine-based chemotherapy in NSCLC patients. PMID- 22306126 TI - A phase I/II study of carboplatin plus gemcitabine for elderly patients with advanced non-small cell lung cancer: West Japan Thoracic Oncology Group Trial (WJTOG) 2905. AB - INTRODUCTION: Monotherapy with a third generation anticancer agent has been regarded as the standard therapy for elderly patients with advanced non-small cell lung cancer (NSCLC). However, it is unclear whether elderly patients with a good performance status can tolerate platinum-doublet chemotherapy like younger patients. METHODS: A combination phase I/II study was conducted in chemo-naive elderly patients with NSCLC to establish the toxicity and maximum tolerated dose (MTD) and to investigate the antitumor activity of carboplatin (CBDCA) plus gemcitabine (GEM). GEM was infused on days 1 and 8, and CBDCA on day 1 every 3 weeks. RESULTS: Seventy-five patients were enrolled. The most frequent toxicities were hematological, especially thrombocytopenia. Three of three patients experienced a dose-limiting toxicity at dose level 3: 1000 mg/m(2) GEM with AUC 5 CBDCA (MTD), and one of seven patients at level 2a: 1000 mg/m(2) GEM with AUC 4 CBDCA (recommended dose). In the phase II study, the overall response rate was 22.2% and the median overall survival time was 14.2 months. CONCLUSIONS: Although the recommended dosage is restricted to a lower level compared to younger patients, combination therapy using CBDCA with GEM is tolerable and promising for elderly patients with advanced NSCLC. PMID- 22306127 TI - Dihydropyrimidine dehydrogenase (DPD) expression is negatively regulated by certain microRNAs in human lung tissues. AB - Dihydropyrimidine dehydrogenase (DPD) is important to the antitumor effect of 5 fluorouracil (5-FU). DPD gene (DPYD) expression in tumors is correlated with sensitivity to 5-FU. Because the 5-FU accumulated in cancer cells is also rapidly converted into inactivated metabolites through catabolic pathways mediated by DPD, high DPD activity in cancer cells is an important determinant of the response to 5-FU. DPD activity is highly variable and reduced activity causes a high risk of 5-FU toxicity. Genetic variation in DPYD has been proposed as the main factor responsible for the variation in DPD activity. However, only a small proportion of the activity of DPD can be explained by DPYD mutations. In this study, we found that DPYD is a target of the following microRNAs (miRNA): miR 27a, miR-27b, miR-134, and miR-582-5p. In luciferase assays with HepG2 cells, the overexpression of these miRNAs was associated with significantly decreased reporter activity in a plasmid containing the 3'-UTR of DYPD mRNA. The level of DPD protein in MIAPaca-2 cells was also significantly decreased by the overexpression of these four miRNAs. The results suggest that miR-27a, miR-27b, miR-134, and miR-582-5p post-transcriptionally regulate DPD protein expression. The levels of miRNAs in normal lung tissue and lung tumors were compared; miR-27b and miR-134 levels were significantly lower in the tumors than normal tissue (3.64 +/- 4.02 versus 9.75 +/- 6.58 and 0.64 +/- 0.75 versus 1.48 +/- 1.39). DPD protein levels were significantly higher in the tumors. Thus, the decreased expression of miR-27b would be responsible for the high levels of DPD protein. This study is the first to show that miRNAs regulate the DPD protein, and provides new insight into 5-FU-based chemotherapy. PMID- 22306128 TI - The validity of ultrasonography in the diagnosis of zygomaticomaxillary complex fractures. AB - The aims of this study were to determine the sensitivity, specificity, positive and negative predictive values of ultrasonography in detecting zygomaticomaxillary complex fractures, and to highlight factors that may affect the validity of ultrasonography in the diagnosis of zygomaticomaxillary complex fracture. Twenty-one patients with suspected fractures of the zygomaticomaxillary complex presenting at the authors' hospital were included in this prospective study. All the patients had plain radiographic and computed tomography (CT) investigations. All underwent ultrasonographic examination of the affected region using an ultrasound machine with a 7.5 MHz probe. The different radiologists were not aware of the results of the other two investigations. Statistical significance was inferred at P<0.05. The validity of ultrasonography varied with fracture sites with a sensitivity of 100% for zygomatic arch fractures, 90% for infraorbital margin fractures and 25% for frontozygomatic suture separation. Specificity was 100% for the three types of fracture. There was no statistically significant difference in the ability of CT scan and ultrasonography to diagnose fractures from various zygomaticomaxillary complex fracture sites (P=0.47). Ultrasonography has proved to be a valid tool for the diagnosis of zygomatic arch and displaced infraorbital margin fractures. PMID- 22306129 TI - CBT for the treatment of child anxiety disorders: a review of why parental involvement has not enhanced outcomes. AB - Anxiety affects 10% of all children and disrupts educational, socio-emotional development and overall functioning of the child and family. Research has shown that parenting factors (i.e. intrusiveness, negativity, distorted cognitions) contribute to the development and maintenance of childhood anxiety. Recent studies have therefore investigated if the treatment effect of traditional cognitive behavioural therapy may be enhanced by adding a parental component. However, randomised controlled trials have not shown unequivocal support for this assumption. The results are inconsistent and ambiguous. This article investigates possible reasons for this inconsistency and in particular differences in methodology and the theoretical relevance of the applied parental components are highlighted as possible contributory factors. Another factor is that treatment effect is mainly measured by change in the child's diagnostic status rather than changes in parental or family functioning. PMID- 22306130 TI - Psychometric properties of the Brazilian version of the Obsessive Beliefs Questionnaire (OBQ-44). AB - The present study was designed to assess the psychometric properties of the Brazilian version of the Obsessive Beliefs Questionnaire (OBQ-44) in 104 patients with obsessive compulsive disorder (OCD) at the Hospital de Clinicas de Porto Alegre. The secondary objective was to ascertain whether a decline in OBQ-44 scores occurs after cognitive-behavioral group therapy (CBGT). Factor analysis identified three dysfunctional belief domains from the original scale. Internal consistency and reproducibility were very good and good, respectively. Sensitivity to treatment change (cognitive-behavioral group therapy) was good, and pre-post intervention standardized effect sizes (Cohen's d) were strong. The OBQ-44 plays an important role in this setting; as a user-friendly, self administered instrument that lists the most common dysfunctional beliefs of OCD patients, it enables healthcare providers to assess whether their patients' beliefs change after treatment. PMID- 22306131 TI - Psychometric properties of the GAD-Q-IV and DERS in older, community-dwelling GAD patients and controls. AB - Thirty-seven community-dwelling, older generalized anxiety disorder (GAD) patients and 37 nonanxious controls completed the Generalized Anxiety Disorder Questionnaire for DSM-IV (GAD-Q-IV; Newman et al., 2002), the Difficulties in Emotion Regulation Scale (DERS; Gratz & Roemer, 2004), and other measures of anxiety and depression. The GAD-Q-IV and DERS were assessed for internal consistency reliability, construct validity, and test-retest reliability, with results indicating good psychometric performance. Receiver operating characteristic (ROC) analysis conducted on the full sample suggested that the optimal GAD-Q-IV cutoff for classifying GAD cases was 3.71, with .97 sensitivity and .92 specificity. The cutoff score for classifying those participants with GAD and comorbid conditions was higher, however. ROC analysis with the full sample revealed an optimal DERS cutoff score of 62.5, with .76 sensitivity and .86 specificity. Findings support the use of the GAD-Q-IV and DERS as screening instruments for GAD in older, community-dwelling adults in a research setting. PMID- 22306132 TI - Functional impairment in social anxiety disorder. AB - The present study examined functional impairment among treatment seekers with social anxiety disorder (SAD). We investigated the effects of diagnostic subtypes of SAD and comorbidity with mood and anxiety disorders on impairment. In addition, we used cluster analysis procedures to empirically identify subgroups of individuals with distinct patterns of impairment. Participants were 216 treatment-seeking individuals with SAD. Clinical interviews were undertaken to determine diagnoses of anxiety disorders and major depressive disorder, and a battery of self-report measures was administered to index symptoms of social anxiety, depression and extent of impairment. Results indicated that individuals with the generalized subtype of SAD had greater impairment in all three life domains compared to individuals with the nongeneralized subtype. Comorbidity with mood disorders was associated with greater impairment than SAD alone, but comorbidity with anxiety disorders was not. Four distinct impairment profiles emerged from the cluster analysis: primary work/studies impairment, primary social life impairment, both work/studies and social impairment, and impairment in all domains. Findings from this study suggest that SAD is associated with substantial impairment across multiple domains, and that individuals with SAD present diverse impairment profiles. These profiles may inform subtyping of the disorder as well as therapeutic interventions. PMID- 22306133 TI - Dimensions of anxiety sensitivity in the anxiety disorders: evaluation of the ASI 3. AB - Anxiety sensitivity (AS), the fear of sensations of anxious arousal based on beliefs about their harmful consequences, is increasingly recognized as a multidimensional construct. The recently developed Anxiety Sensitivity Index-3 [ASI-3; Taylor, S., Zvolensky, M., Cox, B., Deacon, B., Heimberg, R., Ledley, D. R., et al. (2007). Robust dimensions of anxiety sensitivity: Development and initial validation of the Anxiety Sensitivity Index-3 (ASI-3). Psychological Assessment, 19, 176-188] measures three dimensions of AS: physical concerns, social concerns, and cognitive concerns. The ASI-3 shows promise, although further evaluation of its psychometric properties and validity in independent samples is needed. We evaluated the ASI-3 in a mixed sample of anxiety disorder patients (N=506) and undergraduate student controls (N=315). The measure demonstrated a stable 3-factor structure and sound psychometric properties, with the three factors showing theoretically consistent patterns of associations with anxiety symptoms and diagnoses. ASI-3 total scores were less discriminative. Implications for conceptual models of anxiety are discussed. PMID- 22306134 TI - Examining the factor structure of PTSD between male and female veterans in primary care. AB - The present study assessed potential gender differences between the two prevailing PTSD models - the emotional numbing (King, Leskin, King, & Weathers, 1998) and dysphoria (Simms, Watson, & Doebbelling, 2002) models - in order to establish whether one model is superior with regard to its cross-gender generalizability. The sample included 188 female and 690 male trauma-exposed United States Veterans presenting to Veterans Affairs primary care medical clinics. Multigroup confirmatory factor analyses with covariates (MIMIC models) were conducted using the PTSD Checklist. The covariates included were socio demographic variables and the type of traumatic event experienced. The emotional numbing model was statistically superior for men, but no difference between models was noted for females. After controlling for model covariates, men reported higher item-level severity and women had larger residual error variances and larger factor variances and covariances in the emotional numbing model. These results suggest partial generalizability of the emotional numbing model across gender. PMID- 22306136 TI - Only reflect . . . PMID- 22306135 TI - Alterations of metabolic genes and metabolites in cancer. AB - Altered metabolic regulation has long been observed in human cancer and broadly used in the clinic for tumor detection. Two recent findings--the direct regulation of metabolic enzymes by frequently mutated cancer genes and frequent mutations of several metabolic enzymes themselves in cancer--have renewed interest in cancer metabolism. Supporting a causative role of altered metabolic enzymes in tumorigenesis, abnormal levels of several metabolites have been found to play a direct role in cancer development. The alteration of metabolic genes and metabolites offer not only new biomarkers for diagnosis and prognosis, but also potential new targets for cancer therapy. PMID- 22306137 TI - Why is primary care still so unpopular? PMID- 22306138 TI - Entry into GP training at ST2 and above? PMID- 22306139 TI - Embracing reflective practice. PMID- 22306140 TI - Testing the test: an analysis of the MRCGP Applied Knowledge Test as an assessment tool. AB - The new membership examination of the Royal College of General Practitioners (MRCGP) has been in existence since autumn 2007. The MRCGP assessments aim to assure the RCGP of the competence of a general practitioner specialty trainee (GPST). Once the MRCGP is obtained, the GPST is then able to apply for a certificate of completion of training (CCT) from the General Medical Council (GMC). The MRCGP demonstrates the commonly described educational theory model of Miller's pyramid (see Figure 1). The Applied Knowledge Test (AKT), as the name suggests, aims for more than mere recall and arguably is at the 'knows how' level. Current literature suggests that the 'shows how' level constitutes competency-based assessment rather than performance. In the MRCGP, this takes the form of Clinical Skills Assessment (CSA). The level of 'does' is assessed via workplace-based assessments. These are performed throughout the three years of GPST training. They also take into account that the skill of performance incorporates not only competence, but also a combination of other influences mentioned in the Cambridge model for delineating performance and competence. This article will focus on the AKT. It is a three-hour 200-item multi-choice question (MCQ) examination that covers the three broad domains described in Box 1. The questions are in one of three formats: single best answer, extended matching questions and completion of algorithms. Literature exists that looks at the characteristics of a good assessment system. However, it is the work of van der Vleuten that is widely cited. He suggested that validity, reliability, educational impact, cost-effectiveness and acceptability must all be considered when constructing an assessment. I will now focus on the AKT in relation to each of the factors. PMID- 22306141 TI - How competent do general practice residents feel and why? AB - BACKGROUND: General practice residency aims to produce competent general practitioners (GPs) who will practice independently, i.e. who demonstrate adequate levels of actual and self-perceived competence. PURPOSES: To measure self-perceived competence in GP residents at our institution and explore potential determinants. METHODS: We conducted a cross-sectional study of our GP residents. Self-perceived competence was measured in four domains. Independent variables included gender, postgraduate year, patient contacts, on-call duties, practice of specific tasks, self-assessed effort and knowledge. RESULTS: Between 1.6 and 37.8% of GP residents assessed their competence as less than average. Self-perceived competence was not consistently linked to any of the hypothesised factors. CONCLUSIONS: A significant proportion of residents reported less than satisfactory levels of self-perceived competence. Longitudinal studies should be conducted as well as qualitative studies focusing on the role of other factors in the development of high levels of self-perceived competence during general practice training. PMID- 22306142 TI - Practice-based small group learning in GP specialty training. AB - INTRODUCTION: Practice-based small group learning (PBSGL) is an approach to continuing professional development (CPD) for general practitioners (GPs) that originated in Canada. It involves small groups of GPs who work through clinical modules. PBSGL is now an established method of learning in Scotland, found to be effective in GP, practice nurse and multi-professional cohorts. However, the effectiveness of PBSGL has not been examined in GP specialty training, where it is becoming widely employed. This research aimed to explore GP Specialty Trainees' (GPSTs') perspectives of the impact of PBSGL on curriculum needs, preparation for independent practice, and facilitator learning. METHODS: To avoid the risk of extrapolating assumptions from others who have used PBSGL as a learning strategy, this study adopted a qualitative approach, and conducted one to-one interviews with 16 GPSTs from a range of Scottish deaneries and stages in training. Data took the form of verbatim transcripts, and the constant comparative technique from grounded theory was used to analyse the data, through the establishment of codes and categories. RESULTS: Findings were arranged in four main areas: * learning as a group was appreciated at this career stage, and group membership should consist of trainees at a similar career stage, as this supports psychological safety * PBSGL helped in locating a 'one best way' for future care planning, but was also used to find alternatives to trainees' current approaches * discussion during PBSGL helped GPSTs devise plans for how they would handle patients in the future * some facilitators moderated their involvement for the perceived benefit of the group. DISCUSSION AND CONCLUSION: Learning is experienced in a very unique way for GPSTs, and the views of the cohort are formed on the basis of the delicate stage in their career. Aiding the transition from structured education into independent practice is a more immediate need for GPSTs than curriculum needs. PMID- 22306143 TI - General practice: the DREEM attachment? Comparing the educational environment of hospital and general practice placements. AB - The clinical learning environment is changing. General practice placements are now a fundamental part of undergraduate medical education. There is growing recognition that changes in hospital work practices are altering the breadth of exposure available to students. Surprisingly little work has been done comparing the quality of clinical placements between the hospital and community using validated tools. Such comparisons inform curriculum planning and resource allocation. The aim of this study was to compare the quality of the educational environment experienced by junior medical students during hospital and general practice placements using a widely used tool. Following the introduction of a new integrated curriculum, all Year 3 students (n=108) completed a standardised evaluation instrument, the Dundee Ready Education Environment Measure (DREEM) at the end of each of their clinical attachments (two different hospital sites and one in general practice), giving a total of 324 questionnaires. All forms were analysed and input into Graphpad INSTAT version 3. Total DREEM scores as well as subscale scores were calculated for each site. These were compared across sites using a Mann-Whitney U non-parametric test. By comparison with international standards, clinical attachments in our new integrated curriculum were rated highly. In particular, attachments in general practice scored highly with a mean score of 156.6 and perform significantly better (P < 0.01) when compared with the mean score for hospital rotations of 149.0. Significant differences between general practice and hospital rotations exist in the domains of students' perceptions of atmosphere and students' social self-perceptions. Finally, significant differences also emerged in students' perceptions of teachers in general practice when compared to those in the hospital setting. These findings provide evidence of the high-quality educational environment afforded students in primary care. They challenge the traditional emphasis on hospital-based teaching and preempt the question - Is the community a better place for junior students to learn? PMID- 22306144 TI - A consultation navigation tool: an aid for teaching consultation skills. PMID- 22306145 TI - Communication skills and team-building for receptionists and ancillary staff. PMID- 22306146 TI - A pilot learning set for newly appointed GPs and hospital consultants. PMID- 22306147 TI - Using the learning log to encourage reflective practice. PMID- 22306148 TI - Be a good mentor. PMID- 22306149 TI - Palliative care training for general practice specialty trainees in the East of England. PMID- 22306150 TI - The impact on the educators of 'complex fails' in the MRCGP: ensuring systems learning through significant event auditing. PMID- 22306151 TI - Technology-enhanced learning. PMID- 22306152 TI - FLOTAC can detect parasitic and pseudoparasitic elements in reptiles. AB - Reptiles have increased in popularity worldwide; snakes and lizards are frequently used as pets. As a consequence of their popularity, the interest of the scientific community in these animals has increased. In order to acquire epidemiological data on the parasitic infections affecting reptiles in Italy a survey was carried out in 125 snakes and 25 lizards bred in the Campania region of southern Italy. Individual fecal samples were collected and FLOTAC was used for copromicroscopic diagnosis. Eimeriidae, oxyurids, strongylids, other gastro intestinal nematodes and pulmonary nematodes were the most representative parasites found. Eggs of pseudoparasites (mites, oxyurids and trichurids affecting rodents) were also found. The use of FLOTAC for diagnosis of parasitic infections in reptiles has demonstrated to be a rapid and sensitive test to improve diagnosis and acquire new information on the parasitological fauna of reptiles. PMID- 22306153 TI - Minocycline ameliorates LPS-induced inflammation in human monocytes by novel mechanisms including LOX-1, Nur77 and LITAF inhibition. AB - BACKGROUND: Minocycline exhibits anti-inflammatory properties independent of its antibiotic activity, ameliorating inflammatory responses in monocytes and macrophages. However, the mechanisms of minocycline anti-inflammatory effects are only partially understood. METHODS: Human circulating monocytes were cultured in the presence of lipopolysaccharide (LPS), 50 ng/ml, and minocycline (10-40 MUM). Gene expression was determined by RT-PCR, cytokine and prostaglandin E(2) (PGE(2)) release by ELISA, protein expression, phosphorylation and nuclear translocation by Western blotting. RESULTS: Minocycline significantly reduced the inflammatory response in LPS-challenged monocytes, decreasing LPS-induced transcription of pro-inflammatory tumor-necrosis factor alpha (TNF-alpha), interleukin-1 beta, interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2), and the LPS-stimulated TNF-alpha, IL-6 and PGE(2) release. Minocycline inhibited LPS induced activation of the lectin-like oxidized low density lipoprotein receptor-1 (LOX-1), NF-kappaB, LPS-induced TNF-alpha factor (LITAF) and the Nur77 nuclear receptor. Mechanisms involved in the anti-inflammatory effects of minocycline include a reduction of LPS-stimulated p38 mitogen-activated protein kinase (p38 MAPK) activation and stimulation of the phosphoinositide 3-kinase (PI3K)/Akt pathway. CONCLUSIONS: We provide novel evidence demonstrating that the anti inflammatory effects of minocycline in human monocytes include, in addition to decreased NF-kappaB activation, abrogation of the LPS-stimulated LOX-1, LITAF, Nur77 pathways, p38 MAPK inhibition and PI3K/Akt activation. Our results reveal that minocycline inhibits points of convergence of distinct and interacting signaling pathways mediating multiple inflammatory signals which may influence monocyte activation, traffic and recruitment into the brain. GENERAL SIGNIFICANCE: Our results in primary human monocytes contribute to explain the profound anti-inflammatory and protective effects of minocycline in cardiovascular and neurological diseases and may have direct translational relevance. PMID- 22306154 TI - Quantitative molecular profiling of biomarkers for pancreatic cancer with functionalized quantum dots. AB - Applications in nanomedicine, such as diagnostics and targeted therapeutics, rely on the detection and targeting of membrane biomarkers. In this article we demonstrate absolute quantitative profiling, spatial mapping, and multiplexing of cancer biomarkers using functionalized quantum dots (QDs). We demonstrate highly selective targeting molecular markers for pancreatic cancer with extremely low levels of nonspecific binding. We confirm that we have saturated all biomarkers on the cell surface, and, in conjunction with control experiments, extract absolute quantitative values for the biomarker density in terms of the number of molecules per square micron on the cell surface. We show that we can obtain quantitative spatial information of biomarker distribution on a single cell, important because tumors' cell populations are inherently heterogeneous. We validate our quantitative measurements (number of molecules per square micron) using flow cytometry and demonstrate multiplexed quantitative profiling using color-coded QDs. FROM THE CLINICAL EDITOR: This paper demonstrates a nice example for quantum dot-based molecular targeting of pancreatic cancer cells for advanced high sensitivity diagnostics and potential future selective therapeutic purposes. PMID- 22306155 TI - Gold nanoparticles: the importance of physiological principles to devise strategies for targeted drug delivery. AB - Nanotechnology and its promise for clinical translation to targeted drug delivery with limited accompanying toxicity provide exciting research opportunities that demand multidisciplinary approaches. To make rapid progress in the design of nano platforms for drug delivery and toward their use in the clinic, basic and mechanistic studies must first be tested in vitro and then progress to in vivo studies in animal models, incorporating an understanding of body functioning. Recently, gold nanoparticles (Au NPs) have gained much attention as model drug delivery platforms because of their advantageous surface characteristics that allow easy functionalization with chemical and biological molecules and also due to their apparently low toxicity. In this study we review recent in vitro and in vivo research progress with Au NPs as drug delivery platforms and suggest experimental strategies for future studies for efficacious, targeted delivery. PMID- 22306156 TI - Disassembly and reassembly improves morphology and thermal stability of human papillomavirus type 16 virus-like particles. AB - Recombinant human papillomavirus (HPV) 16 L1 protein self-assembles into virus like particles (VLPs) with diameters of 40 to 60 nm, which are key components in prophylactic HPV vaccines. Marked improvement in morphology and thermal stability on VLP disassembly and reassembly was demonstrated at production scale. Differential scanning calorimetry showed enhanced conformational stability as indicated by the unfolding temperatures and peak heights/areas. Cloud point studies indicated (1) a much lower propensity for post-reassembly VLPs to aggregate during a time course study and (2) much higher cloud point temperatures. In-solution atomic force microscopy showed more uniform size distribution and fully closed particles, with evidence of virion-like assembly revealed by the structural details from a single particle image. Similar approaches for the reassembly of other recombinant VLPs with intrinsic conformational switches would be expected to improve the particle properties and render nanoparticles more suitable for use as vaccines or therapeutics. FROM THE CLINICAL EDITOR: The authors of this study demonstrated that recombinant human papillomavirus 16 L1 protein self-assembles into virus-like particles (VLPs) with marked improvement in morphology and thermal stability on VLP disassembly and reassembly at production scale. This is expected to render these nanoparticles more suitable for use as vaccines or therapeutics. PMID- 22306157 TI - WITHDRAWN: A novel therapeutic system for malignant glioma: nanoformulation, pharmacokinetic, and anticancer properties of cell-nano-drug delivery. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 22306158 TI - Peptide PHSCNK as an integrin alpha5beta1 antagonist targets stealth liposomes to integrin-overexpressing melanoma. AB - As an integrin alpha(5)beta(1) antagonist, N-acetyl-proline-histidine-serine cysteine-asparagine-amide (Ac-PHSCN-NH(2)) is currently in phase II trials for various cancer therapies. In this study Ac-PHSCNK-NH(2) (PHSCNK) was used as a novel homing peptide to prepare ligand-targeted liposomes loaded with doxorubicin (PHSCNK-PL-DOX), with the hypothesis that the therapy target of integrin alpha(5)beta(1) may also serve as a delivery target. The stealth liposomes loaded with doxorubicin (PL-DOX) were used as the control. PHSCNK-PL-DOX demonstrated an enhanced intracellular uptake and a greater cytotoxicity against melanoma B16F10 cells in comparison with PL-DOX. The novel targeted formulation displayed stronger tumor inhibition and prolonged survival time in comparison with controls in C57BL/6 mice bearing B16F10 tumors, and it exhibited less heart toxicity in hematoxylin-eosin (H&E) staining of tissues. Taking the pharmacokinetics and biodistribution results into account, the authors conclude that alpha(5)beta(1) integrin-mediated liposomes might be used as a potential delivery system for targeted tumor therapy. FROM THE CLINICAL EDITOR: Lactosyl-norcantharidin TMC nanoparticles were found superior in comparison with Lac-NCTD and Lac-NCTD chitosan nanoparticles from the standpoint of antitumor activity on murine hepatocarcinoma 22 subcutaneous model. PMID- 22306160 TI - Mouse respiratory cilia with the asymmetric axonemal structure on sparsely distributed ciliary cells can generate overall directional flow. AB - Mucociliary clearance on the surface of the tracheal lumen is an important component of lung defense against dust mites and viruses. However, the axonemal structure that achieves effective ciliary motion, and the mechanisms by which discretely distributed ciliary cells generate directional flow are unknown. In this study, we examined individual ciliary motion with 7- to 9-nm spatial precision by labeling the ciliary tip with quantum dots and detected an asymmetric beating pattern. Cryo-electron tomography revealed that the densities of two inner dynein arms were missing from at least 2 doublet microtubules in the axonemal structure. Although the flow directions generated by individual ciliated cells were unsteady and diverse, the time- and space-averaged velocity field was found to be directional. These results indicate that the asymmetric ciliary motion is driven by the asymmetric axonemal structure, and it generates overall directional flow from the lungs to the oropharynx on sparsely distributed ciliated cells. FROM THE CLINICAL EDITOR: The authors of this study utilized quantum dots in determining the kinetics of ciliary motion in mouse respiratory cilia with 7- to 9-nm spatial precision. PMID- 22306159 TI - Gene delivery nanoparticles specific for human microvasculature and macrovasculature. AB - Endothelial cell dysfunction is a critical component of ocular diseases such as age-related macular degeneration and diabetic retinopathy. An important limitation in endothelial cell research is the difficulty in achieving efficient transfection of these cells. A new polymer library was here synthesized and utilized to find polymeric nanoparticles that can transfect macrovascular (human umbilical vein, HUVECs) and microvascular (human retinal, HRECs) endothelial cells. Nanoparticles were synthesized that can achieve transfection efficiency of up to 85% for HRECs and 65% for HUVECs. These nanoparticle systems enable high levels of expression while avoiding problems associated with viral gene delivery. The polymeric nanoparticles also show cell-specific behavior, with a high correlation between microvascular and macrovascular transfection (R(2) = 0.81) but low correlation between retinal endothelial and retinal epithelial transfection (R(2) = 0.21). These polymeric nanoparticles can be used in vitro as experimental tools and potentially in vivo to target and treat vascular-specific diseases. FROM THE CLINICAL EDITOR: Polymeric nanoparticles were synthesized with the goal of transfecting endothelial cells, which are commonly considered difficult targets. The authors report excellent transfection efficiency of up to 85% for human retinal and 65% for human umbilical vein endothelial cells. These NPs can be used in vitro as experimental tools and potentially in vivo to target and treat vascular-specific diseases. PMID- 22306161 TI - Inexpensive non-toxic flocculation of microalgae contradicts theories; overcoming a major hurdle to bulk algal production. AB - There are two major energy and cost constraints to bulk production of single cell microalgae for biofuels or feed: expensive culture systems with high capital costs and high energy requirements for mixing and gas exchange; and the cost of harvesting using high-speed continuous centrifugation for dewatering. This report deals with the latter; harvesting by flocculation where theory states that alkaline flocculants neutralize the repelling surface charge of algal cells, allowing them to coalesce into a floc. It had been assumed that with such electrostatic flocculation, the more cells to be flocculated, the more flocculant needed, in a linear stoichiometric fashion, rendering flocculation overly expensive. Counter to theory of electrostatic flocculation, we find that the amount of alkaline flocculant needed is a function of the logarithm of cell density, with dense cultures requiring an order of magnitude less base than dilute suspensions, with flocculation occurring at a lower pH. Various other theories abound that flocculation can be due to multi-valent cross-linking, or co precipitation with phosphate or with magnesium and calcium, but are clearly not relevant with the flocculants we used. Monovalent bases that cannot cross-link or precipitate phosphate work with the same log-linear stoichiometry as the divalent bases, obviating those theories, leaving electrostatic flocculation as the only tenable theory of flocculation with the materials used. The cost of flocculation of dense cultures with this procedure should be below $1.00/T algae for mixed calcium:magnesium hydroxides. PMID- 22306162 TI - Advancements and future directions in enzyme technology for biomass conversion. AB - Enzymatic hydrolysis of pre-treated lignocellulosic biomass is an ideal alternative to acid hydrolysis for bio-ethanol production, limited primarily by pre-treatment requirements and economic considerations arising from enzyme production costs and specific activities. The quest for cheaper and better enzymes has prompted years of bio-prospecting, strain optimization through genetic engineering, enzyme characterization for simple and complex lignocellulosic feedstock, and the development of pre-treatment strategies to mitigate inhibitory effects. The recent shift to systematic characterizations of de novo mixtures of purified proteins is a promising indicator of maturation within this field of study, facilitating progression towards feedstock assay based rapid enzyme mixture optimization. It is imperative that international standards be developed to enable meaningful comparisons between these studies and the construction of a database of enzymatic activities and kinetics, aspects of which are explored here-in. Complementary efforts to improve the economic viability of enzymatic hydrolysis through process integration and reactor design are also considered, where membrane-confinement shows significant promise despite the associated technological challenges. Significant advancements in enzyme technology towards the economic conversion of lignocellulosic biomass should be expected within the next few years as systematic research in enzyme activities conforms to that of traditional reaction engineering. PMID- 22306163 TI - Biorefining: thermochemical and enzymatic biomass conversion: selected papers from the International Conference on Biomass and Energy Technologies (ICBT2010), Beijing, China, August 20-22, 2010. PMID- 22306164 TI - A sustainable woody biomass biorefinery. AB - Woody biomass is renewable only if sustainable production is imposed. An optimum and sustainable biomass stand production rate is found to be one with the incremental growth rate at harvest equal to the average overall growth rate. Utilization of woody biomass leads to a sustainable economy. Woody biomass is comprised of at least four components: extractives, hemicellulose, lignin and cellulose. While extractives and hemicellulose are least resistant to chemical and thermal degradation, cellulose is most resistant to chemical, thermal, and biological attack. The difference or heterogeneity in reactivity leads to the recalcitrance of woody biomass at conversion. A selection of processes is presented together as a biorefinery based on incremental sequential deconstruction, fractionation/conversion of woody biomass to achieve efficient separation of major components. A preference is given to a biorefinery absent of pretreatment and detoxification process that produce waste byproducts. While numerous biorefinery approaches are known, a focused review on the integrated studies of water-based biorefinery processes is presented. Hot-water extraction is the first process step to extract value from woody biomass while improving the quality of the remaining solid material. This first step removes extractives and hemicellulose fractions from woody biomass. While extractives and hemicellulose are largely removed in the extraction liquor, cellulose and lignin largely remain in the residual woody structure. Xylo-oligomers, aromatics and acetic acid in the hardwood extract are the major components having the greatest potential value for development. Higher temperature and longer residence time lead to higher mass removal. While high temperature (>200 degrees C) can lead to nearly total dissolution, the amount of sugars present in the extraction liquor decreases rapidly with temperature. Dilute acid hydrolysis of concentrated wood extracts renders the wood extract with monomeric sugars. At higher acid concentration and higher temperature the hydrolysis produced more xylose monomers in a comparatively shorter period of reaction time. Xylose is the most abundant monomeric sugar in the hydrolysate. The other comparatively small amounts of monomeric sugars include arabinose, glucose, rhamnose, mannose and galactose. Acetic acid, formic acid, furfural, HMF and other byproducts are inevitably generated during the acid hydrolysis process. Short reaction time is preferred for the hydrolysis of hot-water wood extracts. Acid hydrolysis presents a perfect opportunity for the removal or separation of aromatic materials from the wood extract/hydrolysate. The hot-water wood extract hydrolysate, after solid-removal, can be purified by Nano-membrane filtration to yield a fermentable sugar stream. Fermentation products such as ethanol can be produced from the sugar stream without a detoxification step. PMID- 22306165 TI - Closed photobioreactors for production of microalgal biomasses. AB - Microalgal biomasses have been produced industrially for a long history for application in a variety of different fields. Most recently, microalgae are established as the most promising species for biofuel production and CO(2) bio sequestration owing to their high photosynthesis efficiency. Nevertheless, design of photobioreactors that maximize solar energy capture and conversion has been one of the major challenges in commercial microalga biomass production. In this review, we systematically survey the recent developments in this field. PMID- 22306166 TI - Synthesis of bioethanol from biomass-derived syngas over carbon nanotube/silica supported catalyst. AB - Multi-walled carbon nanotubes (MWNTs) were functionalized with pyrogallol and used in a composite with silica as a support for a Cu-Co based catalyst. The catalysts were characterized using X-ray diffraction, transmission electron microscopy, and H(2) temperature programmed reduction. The effects of pyrogallol and the weight ratio of silica to MWNTs on the performance of the catalyst were studied in a fixed bed reactor. The increase of the amount of MWNTs in the catalyst support was found to favor decreased methanol production and increased production of C2+ alcohols. Using pyrogallol in catalyst preparation was also found to increase the production of C2+ alcohols. It was concluded that pyrogallol improves the distribution and uniformity of metal particles on the support, decreases the size of metal particles and increasing the rate of catalytic reduction. PMID- 22306167 TI - Biorefinery of sweet sorghum stem. AB - Sweet sorghum has been considered as a viable energy crop for alcohol fuel production. This review discloses a novel approach for the biorefining of sweet sorghum stem to produce multiple valuable products, such as ethanol, butanol and wood plastic composites. Sweet sorghum stem has a high concentration of soluble sugars in its juice, which can be fermented to produce ethanol by Saccharomyces cerevisiae. In order to obtain high ethanol yield and fermentation rates, concentrated juice with an initial total sugar concentration of 300gL(-1) was fermented. The maximum ethanol concentration after 54h reached 140gL(-1) with a yield of 0.49g ethanol per g consumed sugar, which is 97% of the theoretical value. Sweet sorghum bagasse, obtained from juice squeezing, was pretreated by acetic acid to hydrolyze 80-90% of the contained hemicelluloses. Using this hydrolysate as raw material (total sugar 55gL(-1)), 19.21gL(-1) total solvent (butanol 9.34g, ethanol 2.5g, and acetone 7.36g) was produced by Clostridium acetobutylicum. The residual bagasse after pretreatment was extruded with PLA in a twin-screw extruder to produce a final product having a PLA: fiber ratio of 2:1, a tensile strength of 49.5M and a flexible strength of 65MPa. This product has potential use for applications where truly biodegradable materials are required. This strategy for sustainability is crucial for the industrialization of biofuels from sweet sorghum. PMID- 22306168 TI - Recent advances in membrane technologies for biorefining and bioenergy production. AB - The bioeconomy, and in particular, biorefining and bioenergy production, have received considerable attention in recent years as a shift to renewable bioresources to produce similar energy and chemicals derived from fossil energy sources, represents a more sustainable path. Membrane technologies have been shown to play a key role in process intensification and products recovery and purification in biorefining and bioenergy production processes. Among the various separation technologies used, membrane technologies provide excellent fractionation and separation capabilities, low chemical consumption, and reduced energy requirements. This article presents a state-of-the-art review on membrane technologies related to various processes of biorefining and bioenergy production, including: (i) separation and purification of individual molecules from biomass, (ii) removal of fermentation inhibitors, (iii) enzyme recovery from hydrolysis processes, (iv) membrane bioreactors for bioenergy and chemical production, such as bioethanol, biogas and acetic acid, (v) bioethanol dehydration, (vi) bio-oil and biodiesel production, and (vii) algae harvesting. The advantages and limitations of membrane technologies for these applications are discussed and new membrane-based integrated processes are proposed. Finally, challenges and opportunities of membrane technologies for biorefining and bioenergy production in the coming years are addressed. PMID- 22306169 TI - Normal range of serum Amphiregulin in healthy adult human females. AB - OBJECTIVES: Prior to large studies in breast cancer patients, we have sought to establish the normal range of a potential serum biomarker, Amphiregulin, in healthy women and to determine whether sampling during the menstrual cycle influences the detected Amphiregulin levels. DESIGN AND METHODS: Serum Amphiregulin levels were quantified using a commercially available ELISA in 85 normal female donors. RESULTS: The range of circulating Amphiregulin was 0-4467 pg/mL. The majority of women had no detectable circulating Amphiregulin (n=54), and only five women had levels exceeding 500 pg/mL. Serum Amphiregulin levels did not vary significantly during the menstrual cycle (n=7 women). CONCLUSIONS: Detection of circulating Amphiregulin in a significant minority of healthy women suggests that it may not have the specificity necessary for a population screening tool; however its potential utility for monitoring response to treatment or disease progression should be examined in breast cancer cases. PMID- 22306170 TI - N-terminal and C-terminal fragments of IGFBP-4 as novel biomarkers for short-term risk assessment of major adverse cardiac events in patients presenting with ischemia. AB - OBJECTIVES: Pregnancy Associated Plasma Protein A (PAPP-A)-derived N- and C terminal fragments of IGF-binding protein-4 (NT- and CT-IGFBP-4) released from vulnerable atherosclerotic plaques are proposed to be used for cardiovascular risk assessment. DESIGN AND METHODS: NT- and CT-IGFBP-4 were measured by novel immunoassays in EDTA-plasma of 180 patients admitted to the emergency department with symptoms of myocardial ischemia but without ST-segment elevation. Six-month incidence of major adverse cardiac events (MACE), including myocardial infarction, cardiac death, percutaneous coronary interventions, and coronary artery bypass grafting was recorded. RESULTS: Sixteen patients met the endpoint. NT- and CT-IGFBP-4 were strong predictors of MACE: area under ROC curve (AUC) 0.856 and 0.809, respectively. NT-IGFBP-4 concentrations>=214MUg/L and CT-IGFBP-4 concentrations>=124MUg/L were associated with increased risk of future MACE: adjusted hazard ratio 13.79 and 7.93, respectively. CONCLUSIONS: IGFBP-4 fragments can be utilized as biomarkers for MACE prediction in patients with suspected myocardial ischemia. PMID- 22306171 TI - Profound hypoglycemia presents with reversible symmetrical ADC signal changes isolated to eloquent cortex of the parietal lobe. AB - MRI diffusion/ADC signal change with reversal, symmetrically isolated to the cortex of the precentral gyri in profound hypoglycemia has not been previously described. We present a case in which minimal cortical signal change without deep gray matter involvement and subsequent reversal occurred without significant clinical improvement. Correlation of the reversal of diffusion/ADC signal to findings by EEG evaluation has been described in animal studies and not in humans before. PMID- 22306172 TI - Synthesis and biological evaluation of pyrimidine nucleoside monophosphate prodrugs targeted against influenza virus. AB - Uridine-based nucleoside analogues have often been found to have relatively poor antiviral activity. Enzymatic assays, evaluating inhibition of influenza virus RNA polymerase, revealed that some uridine triphosphate derivatives displayed inhibitory activity on UTP incorporation into viral RNA. Here we report the synthesis, antiviral activity and enzymatic evaluation of novel ProTides designed to deliver the activated (monophosphorylated) uridine analogues inside the influenza virus-infected cells. After evaluation of the activation profile we identified two ProTides with moderate antiviral activity in MDCK cells (23a, EC(99)=49 +/- 38 MUM and 23b, EC(99)>=81 MUM) while the corresponding nucleoside analogue (2'-fluoro-2'-deoxyuridine) was inactive. Thus, at least in these cases the poor antiviral activity of the uridine analogues may be ascribed to poor phosphorylation. PMID- 22306173 TI - In vitro replication of bovine herpesvirus types 1 and 5. AB - The aim of this work was to study the in vitro replication of bovine herpesvirus types 1 and 5 (BoHV-1 and 5) at the beginning and end of the logarithmic growth phase of Madin-Darby Bovine Kidney (MDBK) cells. The replication kinetics and size of lysis and infection plaques of the field isolates 09/210 (BoHV-1) and 97/613 (BoHV-5) and the reference strains BoHV-1.1 Los Angeles 38 (LA38), BoHV 1.1 Cooper, BoHV-5a N569 and BoHV-5b A663 were evaluated. The highest mean virus titre was recorded for N569, followed by LA38 and 97/613. For most of the viruses, the virus titre values increased from 24 h post-infection (hpi) up to 48 hpi and then, they remained unchanged up to 72 hpi. However, the virus titre for 09/210 was significantly lower and a slight, steady increase was observed from 24 to 72 hpi. Furthermore, the largest lysis and infection plaques were recorded for 97/613 and LA38, respectively. According to this work, it is evident that there is a relationship between the replication of BoHV and the multiplication stage of MDBK cells. The results of this study contribute to the understanding of the replication behaviour in cell cultures of several strains of BoHV, which is critical for the rational design of in vitro experiments and vaccine production. PMID- 22306174 TI - Penetratin-induced transdermal delivery from H(II) mesophases of sodium diclofenac. AB - Penetratin, a cell penetrating peptide is embedded within a reversed hexagonal (H(II)) mesophase for improved transdermal delivery of sodium diclofenac (Na DFC). The H(II) mesophase serves as the solubilization reservoir and gel matrix whereas penetratin is the transdermal penetration enhancer for the drug. The systems were characterized and the interactions between the components were determined by SAXS, ATR-FTIR and SD-NMR. High affinity of Na-DFC to glycerol monooleate (GMO) was revealed, associated with increasing the order within the water channels. This affinity is enhanced upon heating and seems to be associated with GMO dehydration. Penetratin (PEN) is entrapped at the hydrophilic region of the H(II) mesophase, between the GMO headgroups, reducing the order of the system and decreasing the size of the hexagonal domains. The transdermal delivery rate of Na-DFC through porcine skin, from the H(II) mesophases, was enhanced by PEN and so also the cumulative transport crossing the skin. PEN induced accelerated drug diffusion through the stratum corneum, towards the different skin layers. The transdermal delivery enhancement is explained from the results of the ATR FTIR analysis. It seems that PEN accelerates the structural transition of skin lipids from hexagonal to liquid. The disordering results in enhanced diffusion of Na-DFC through the stratum corneum, followed by enhanced overall penetration of the drug. PMID- 22306175 TI - Technical note and results in the management of anatomical variants of renal vascularisation during endovascular aneurysm repair. AB - INTRODUCTION: The revascularisation of large (>3 mm) renal arteries emerging from the proximal sealing zone or off the aneurismal wall can be challenging during endovascular aortic aneurysm repair. In this article, we describe various endovascular techniques using custom-made endografts to treat these complex variant anatomies. CASES: Nine patients deemed unfit for open repair with unusual renal vascularisation associated with aortic aneurysms were treated by endovascular means. After three-dimensional (3D) reconstructions on a dedicated workstation, custom-made devices were designed and manufactured. The revascularisation of multiple renal arteries and aberrant origins of renal arteries, associated or not with pelvic kidney or horseshoe kidney, was managed using fenestrated and branched endografts. RESULTS: All target vessels were patent on computed tomography (CT) scan and contrast-enhanced ultrasound evaluation before discharge as well as on the 6-month follow-up. One patient presented a decrease of postoperative glomerular filtration rate over 30% but did not require dialysis. No sac enlargement was depicted, and no reintervention was performed during follow-up. Three type 2 endoleaks were diagnosed. CONCLUSION: Endovascular treatment with fenestrated and branched endografts should be considered in challenging renal artery anatomies in patients unfit for open repair. PMID- 22306176 TI - Occupational health care identifies risk for type 2 diabetes and cardiovascular disease. AB - AIMS: To assess the risk for type 2 diabetes (T2D) and cardiovascular disease (CVD) among employees of a Finnish airline; to study the association of shift work with T2D and CVD risk; and to test the feasibility of risk screening in occupational health care setting. METHODS: Altogether 4169 employees were invited for a health check-up and 2312 participated in this study. The check-up included physical examinations, questionnaires on working hours, sleep, and lifestyle, diabetes risk score FINDRISC, and blood tests. Lifestyle counselling was offered for those with increased T2D risk. RESULTS: Altogether 15% of participants had a high T2D risk (FINDRISC>=15 and/or elevated, but non-diabetic blood glucose), and a further 15% had a moderate T2D risk (FINDRISC 10-14 and normal blood glucose). Of those 60% agreed to attend lifestyle counselling. Metabolic syndrome was more common, lipid profile more unfavorable and hsCRP higher by increasing FINDRISC score category. Risk factor profiles linked to shift work status were not self evident. CONCLUSIONS: The renewed health check-up process effectively identified those employees with increased T2D and CVD risk who would benefit from lifestyle intervention. The use of FINDRISC questionnaire was a feasible first-step screening method in occupational health care setting. PMID- 22306177 TI - Synergistic BAR-NPF interactions in actin-driven membrane remodeling. AB - Cell and organelle shape can profoundly influence proper cellular function. In recent years, two machineries have emerged as major regulators of membrane shape: Bin-Amphiphysin-Rvs161/167 (BAR) domain-containing proteins, which induce membrane invaginations or protrusions, and nucleation promoting factors (NPFs), which activate the Arp2/3 complex and are thus responsible for the generation of branched actin networks that push on membranes. Several BAR-NPF interactions have been shown to induce various types of protrusions, such as lamellipodia or filopodia, or invaginations, including trafficking organelles such as caveolae, endosomes and clathrin-coated pits (CCPs). This review focuses on how collaboration between these two interacting machineries, which emerges as a unified mechanism of membrane remodeling, accounts for such a variety of membrane shapes. PMID- 22306178 TI - Depletion of ascorbic acid impairs NK cell activity against ovarian cancer in a mouse model. AB - Ascorbic acid (Vitamin C) administration has been used to prevent infectious diseases in public or as a therapeutic agent by the physicians in treatment of several diseases. Ascorbic acid is also involved in immune cell functions and immune responses, although the mechanisms by which it exerts effects on immune cells against cancer cells are not fully understood at the normal plasma level. In this study, we used the mice lacking l-gulono-gamma-lactone oxidase (Gulo), the enzyme required for the biosynthesis of ascorbic acid, to characterize the effects of ascorbic acid on NK cell cytotoxicity against ovarian cancer cells, MOSECs (murine ovarian surface epithelial cells). Gulo(-/-) mice depleted of ascorbic acid survived for a shorter time than the normal control or Gulo(-/-) mice supplemented with ascorbic acid after tumor challenge regardless of treatment with IL-2. CD69 and NKG2D expression was clearly reduced in NK cells isolated from mice depleted of ascorbic acid as compared to that in the normal control and the mice supplemented with ascorbic acid. We also observed that IFN gamma secretion by NK cells isolated from Gulo(-/-) mice depleted of ascorbic acid was decreased after NK cells were co-cultured with MOSECs. Furthermore, the mRNA expression of perforin and granzyme B genes was also significantly decreased in NK cells isolated from mice depleted of ascorbic acid. Taken together, our results suggest that ascorbic acid at the normal plasma concentration has an essential role in maintaining the NK cytotoxicity against cancer cells. PMID- 22306179 TI - Notch signaling in human development and disease. AB - Mutations in Notch signaling pathway members cause developmental phenotypes that affect the liver, skeleton, heart, eye, face, kidney, and vasculature. Notch associated disorders include the autosomal dominant, multi-system, Alagille syndrome caused by mutations in both a ligand (Jagged1 (JAG1)) and receptor (NOTCH2) and autosomal recessive spondylocostal dysostosis, caused by mutations in a ligand (Delta-like-3 (DLL3)), as well as several other members of the Notch signaling pathway. Mutations in NOTCH2 have also recently been connected to Hajdu Cheney syndrome, a dominant disorder causing focal bone destruction, osteoporosis, craniofacial morphology and renal cysts. Mutations in the NOTCH1 receptor are associated with several types of cardiac disease and mutations in NOTCH3 cause the dominant adult onset disorder CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a vascular disorder with onset in the 4th or 5th decades. Studies of these human disorders and their inheritance patterns and types of mutations reveal insights into the mechanisms of Notch signaling. PMID- 22306180 TI - Notch ligand endocytosis: mechanistic basis of signaling activity. AB - Regulation of Notch signaling is critical to development and maintenance of most eukaryotic organisms. The Notch receptors and ligands are integral membrane proteins and direct cell-cell interactions are needed to activate signaling. Ligand-expressing cells activate Notch signaling through an unusual mechanism involving Notch proteolysis to release the intracellular domain from the membrane, allowing the Notch receptor to function directly as the downstream signal transducer. In the absence of ligand, the Notch receptor is maintained in an autoinhibited, protease resistant state. Genetic studies suggest that Notch ligands require ubiquitylation, epsin endocytic adaptors and dynamin-dependent endocytosis for signaling activity. Here we discuss potential models and supporting evidence to account for the absolute requirement for ligand endocytosis to activate signaling in Notch cells. Specifically, we focus on a role for ligand-mediated endocytic force to unfold Notch, override the autoinhibited state, and activate proteolysis to direct Notch-specific cellular responses. PMID- 22306181 TI - The dynamics of feeding during the introduction to solid food. AB - In the first year of life, infants go through a crucial transition in feeding when they are introduced to solid food. However, the literature is lacking a good description of the changes in feeding behaviors during this transition. The current paper addresses this by means of a multiple case study focusing on how caretaker and infant build a new and effective feeding dialogue after the transition to solid food. It describes the development of stable interaction patterns, as they emerge during this transition. Feeding interactions are studied directly through repeated naturalistic observations. The results show that while the interaction behavior of some caretaker-infant dyads remains variable, others stabilize quickly. However, ultimately most dyads self-organize their behaviors towards a stable feeding dialogue, which is both sensitive and effective. Evidence for the existence of four characteristic patterns was found. We argue that this finding can be interpreted as the result of a co-regulation process of consensual frames. The study also offers a framework for analyzing other processes of co-regulation that occur throughout human development. PMID- 22306182 TI - Shaking things up: young infants' use of sound information for object individuation. AB - A search task was used to assess 5- to 7-month-olds' ability to use property-rich sounds to individuate objects. Results suggest that infants interpret an occlusion event involving two distinct rattle sounds as involving two objects but are unsure of how to interpret two identical rattle sounds. PMID- 22306183 TI - Infant sleep, parental sleep and parenting stress in families of mothers on maternity leave and in families of working mothers. AB - The purpose of the present study was to investigate the links between infants' sleep and their parents' sleep and to assess the links between infant/parent sleep and parenting stress. Furthermore, we explored whether the links between sleep and parenting stress are moderated by maternal leave status. Participants were 50 families with an infant between the ages of 4-5 months. Half of the mothers were on maternity leave while the others returned to work. Parents completed daily sleep logs about infants' and their own sleep for 4 consecutive nights. Each parent also completed the Parenting Stress Index. Infant sleep was associated with sleep of both mothers and fathers, but the correlations with maternal sleep were stronger. Parental perceptions of their infant's sleep as problematic were associated with higher parenting stress. Poorer infant and maternal sleep patterns were associated with parenting stress only in families with mothers on maternity leave, probably because these mothers need to provide intensive caregiving "around the clock" without sufficient opportunities to rest. PMID- 22306184 TI - Ferulic acid prevents the cerebral ischemic injury-induced decreases of astrocytic phosphoprotein PEA-15 and its two phosphorylated forms. AB - Ferulic acid protects neuronal cells against focal cerebral ischemic injury through its anti-oxidative and anti-inflammatory effects. Phosphoprotein enriched in astrocytes 15 (PEA-15) is known to modulate various cellular processes including cell proliferation, apoptosis, and survival. This study was investigated whether ferulic acid can regulate the levels of PEA-15 and its two phosphorylated forms (Ser 104 and Ser 116) in a cerebral ischemic injury model and in neuronal cells exposed to glutamate. A middle cerebral artery occlusion (MCAO) was performed to induce focal cerebral ischemic injury. Adult male rats were immediately treated with vehicle or ferulic acid (100 mg/kg) at the beginning of the MCAO, and then cerebral cortices were collected 24h after MCAO. The decrease in PEA-15 level after ischemic injury was detected using a proteomic approach. Ferulic acid administration prevented the ischemic injury-induced decrease of PEA-15 level. Moreover, Western blot analysis clearly confirmed that ferulic acid attenuates the ischemic injury-induced decreases in PEA-15, phospho PEA-15 (Ser 104), and phospho-PEA-15 (Ser 116) levels. Glutamate exposure induced significant reductions in the levels of PEA-15 and the two phospho-PEA-15 (Ser 104 and Ser 116) in cultured hippocampal neuron, while pretreatment with ferulic acid prevented the glutamate toxicity-induced decreases in these proteins levels. The decrease of phospho-PEA-15 protein level indicates that the anti-apoptotic function of PEA-15 was being inhibited. Thus, these results suggest that ferulic acid protects neuronal cells against ischemic injury by maintenance of phospho PEA-15 protein levels. PMID- 22306185 TI - Effects of different adrenergic blockades on the stress resistance of Wistar rats. AB - The coordinated responses of the sympathoadreno-medullary (SAM) system and hypothalamic-pituitary-adrenal (HPA) axis could improve the organism's capacity to cope with stress, but its underlying mechanism is still unclear. In the present study, 32 Wistar rats were employed and divided into four groups: control, CUMS, PROP and PRAZ. After the chronic unpredicted mild stress (CUMS) model was built in the latter three groups, all animals were exposed to inescapable footshock. We found that alpha(1)-adrenoceptor antagonist prazosin (PRAZ) administration could improve behavior changes, reduce the cellular impairment in brain and inhibit the hyperfunction of HPA axis induced by CUMS exposure. Moreover, it decreased the heat shock protein 70 and inducible nitric oxide synthase expression in different brain areas as subsequently exposed to acute stress. In conclusion, alpha1-adrenoceptor may play a major role in regulating the coordinated responses between two physiological axes and improve the stress resistance. PMID- 22306186 TI - Studying survivors of near-lethal suicide attempts as a proxy for completed suicide in prisons. AB - Suicides in prisons are common. There is a pressing need to understand more about the causes and prevention of prisoner suicides. A particularly informative approach is through studying survivors of near-lethal suicide attempts. However, the extent to which this approach is a good proxy for completed suicide requires verification. In this article we aimed to assess (1) the extent to which male and female prisoners who made near-lethal suicide attempts in prison are similar to prisoners who die by suicide; (2) the suicidal intent of those making near-lethal suicide attempts; and (3) the applicability of the Suicide Intent Scale in prisons. Survivors of near-lethal suicide attempts and prisoners who died by suicide were compared on sociodemographic and criminological characteristics. The suicidal intent of prisoners engaging in near-lethal self-harm was assessed using Beck's Suicide Intent Scale. There were no significant differences when the sociodemographic and criminological profiles of prisoners who made near-lethal suicide attempts and those who died by suicide were compared, except that male prisoners who made near-lethal suicide attempts were somewhat younger. Most prisoners carrying out near-lethal acts had high suicidal intent. However, some questions in the Suicide Intent Scale were inappropriate for assessing intent in prisoners. Prisoners who survive near-lethal self-harm would appear to be a valid proxy for those who die by suicide in prison. The Suicide Intent Scale requires some modifications for use in prisons. PMID- 22306187 TI - Experimental forensic scenes for the characterization of ground-penetrating radar wave response. AB - Over the last few decades, the use of non-intrusive geophysical techniques, which allows for coverage of an entire crime scene in a reasonable amount of time, in forensic investigation has increased. In this study, we analyze the effectiveness of ground-penetrating radar (GPR) in forensics. Experimental scenes were simulated and some of the most commonly buried items in actual crime scenes were introduced, such as bone remains, guns and drug caches. Later, a GPR survey was conducted on the experimental grids with a 500 MHz antenna. The final purpose was to characterize the radar wave response expected for each set of remains to assist with its identification in later actual investigations. The results collected provided promising information that can be used when surveying real cases. Nevertheless, there were some interpretational difficulties regarding the sizes of the items and the electromagnetic properties of the materials. For these cases, finite-difference time-domain modeling was employed to achieve an advanced interpretation of the field data. The simulated models used were built from accurate geometric data provided by photogrammetric methods, which replicate the experimental scenes in fine detail. Furthermore, this approach allowed for the simulation of more realistic models, and the synthetic data obtained provided valuable information for assisting in the interpretation of field data. As a result of this work, it was concluded that GPR can be an effective tool when searching for a variety of materials during a crime scene investigation. PMID- 22306188 TI - Forensic aspects of water intoxication: four case reports and review of relevant literature. AB - Water intoxication (WI) is a rare condition that originates from over-consumption of water, with a potentially fatal outcome. Increased water intake (polydipsia) is followed by urination of high amount of diluted urine (polyuria) which are the main initial symptoms of WI. We present four case reports of WI. Two of them are unusual pediatric clinical cases using medical documentation and police case files, one of which is related to child abuse, and the other to a psychiatric disorder. The other two cases are fatal adult cases submitted to autopsy from a psychiatric hospital. Also, we present a diagnostic algorithm for polydipsia and polyuria before death. WI is usually seen in patients with psychiatric disorders, victims of child abuse or torture, drug abusers or it can be iatrogenically induced. PMID- 22306189 TI - Development of an immunoassay for the differentiation of menstrual blood from peripheral blood. AB - Forensic identification of body fluids is a crucial aspect of the discipline. To date, there are no robust tests to make a distinction between menstrual blood and peripheral blood. Past techniques have fallen short of producing clear and consistent results while present mRNA techniques are still in their infancy. The aim of this study was to develop of an accurate and rapid immunoassay based identification method. Three different targets were evaluated: matrix metalloproteinase 14 (MMP14), oestrogen receptor alpha (ERalpha), and fibrinogen. Cellular or membrane bound antigens were analyzed using immunocytochemical staining while soluble antigens were analyzed by indirect ELISA. Results showed that ERalpha and MMP14 are present in the endometrial cells of menstrual blood but absent in peripheral blood. At a total protein concentration of 10 MUg/mL or lower, fibrinogen was detected in menstrual blood but absent in peripheral. If evaluated on a larger scale, immunoassays may prove to be beneficial in discriminating menstruum and peripheral blood. PMID- 22306190 TI - Perceptual wholes can reduce the conscious accessibility of their parts. AB - Humans can rapidly extract object and category information from an image despite surprising limitations in detecting changes to the individual parts of that image. In this article we provide evidence that the construction of a perceptual whole, or Gestalt, reduces awareness of changes to the parts of this object. This result suggests that the rapid extraction of a perceptual Gestalt, and the inaccessibility of the parts that make up that Gestalt, may in fact reflect two sides of the same coin whereby human vision provides only the most useful level of abstraction to conscious awareness. PMID- 22306191 TI - Pathogenic responses among young adults during the 1918 influenza pandemic. AB - Of the unexplained characteristics of the 1918-19 influenza pandemic, the extreme mortality rate among young adults (W-shaped mortality curve) is the foremost. Lack of a coherent explanation of this and other epidemiologic and clinical manifestations of the pandemic contributes to uncertainty in preparing for future pandemics. Contemporaneous records suggest that immunopathologic responses were a critical determinant of the high mortality rate among young adults and other high risk subgroups. Historical records and findings from laboratory animal studies suggest that persons who were exposed to influenza once before 1918 (e.g., A/H3Nx 1890 pandemic strain) were likely to have dysregulated, pathologic cellular immune responses to infections with the A/H1N1 1918 pandemic strain. The immunopathologic effects transiently increased susceptibility to ultimately lethal secondary bacterial pneumonia. The extreme mortality rate associated with the 1918-19 pandemic is unlikely to recur naturally. However, T-cell-mediated immunopathologic effects should be carefully monitored in developing and using universal influenza vaccines. PMID- 22306192 TI - The genome, evolution and diversity of Mycobacterium ulcerans. AB - Mycobacterium ulcerans (M. ulcerans) causes a devastating infection of the skin and underlying tissue commonly known as Buruli ulcer (BU). Genetic analyses indicate that M. ulcerans has a common ancestor with Mycobacterium marinum (M. marinum) and has diverged from this fish and human pathogen perhaps around a million years ago. M. ulcerans is characterized by minimal genetic diversity and since it has a highly clonal population structure, genetic differences between individual isolates reflect changes that have occurred sequentially from their respective progenitors. This feature, which is shared by other bacterial pathogens with low sequence diversity, such as Yersinia pestis and Bordetella pertussis renders M. ulcerans a promising model to reveal evolutionary mechanisms. Until today transmission pathways and environmental reservoirs of M. ulcerans are not entirely explored. However, comparative genome analysis of closely related M. ulcerans isolates is anticipated to give deeper insights into the population structure of this enigmatic mycobacterium. PMID- 22306193 TI - Effects of an oral MMP-9 and -12 inhibitor, AZD1236, on biomarkers in moderate/severe COPD: a randomised controlled trial. AB - BACKGROUND: There is a pressing need for new forms of treatment for COPD. Based on the known pathophysiology of COPD, inhibition of matrix metalloproteinases is a theoretically promising approach. This Phase IIa study evaluated the effects of AZD1236, a selective MMP-9 and MMP-12 inhibitor, on the biomarkers of inflammation and emphysematous lung tissue degradation in patients with moderate to-severe COPD. METHODS: This was a multinational, randomized, double-blind, placebo-controlled signal-searching study conducted in men and women aged >=40 years with stable moderate-to-severe COPD. After a 2-6-week period to eliminate any remaining effects of previous medication, 55 patients received oral AZD1236 75 mg or matching placebo twice daily for 6 weeks. Differential cell count and TNF-alpha levels in induced sputum and 24-h urinary desmosine excretion were the main study variables, but a range of exploratory biomarkers was also assessed in induced sputum, blood and urine. Secondary variables included lung function and patient-recorded Clinical COPD Questionnaire (CCQ) responses and diary records of symptoms, adverse events, use of rescue medication and AZD1236 plasma concentrations. RESULTS: The majority of variables showed little change compared to placebo although there was a possible, but not statistically significant reduction in urinary desmosine excretion and reductions in the number and percentage of lymphocytes in sputum and blood with AZD1236. No effect was seen on clinical parameters after 6 weeks of treatment. The proportion of patients experiencing adverse events was similar in both treatment groups. CONCLUSIONS: AZD1236 dosed orally at 75 mg twice daily was generally well tolerated over 6 weeks in patients with moderate-to-severe COPD. No clinical efficacy of AZD1236 was demonstrated in this short-term signal-searching study, although possible evidence of an impact on desmosine may suggest the potential value of selective inhibitors of MMPs in the treatment of COPD in longer term trials. PMID- 22306194 TI - Metabolic differences underlying two distinct rat urinary phenotypes, a suggested role for gut microbial metabolism of phenylalanine and a possible connection to autism. AB - A novel explanation is proposed for the metabolic differences underlying two distinct rat urinary compositional phenotypes i.e. that these may arise from differences in the gut microbially-mediated metabolism of phenylalanine. As part of this hypothesis, it is further suggested that elements of the mammalian gut microbiota may convert phenylalanine to cinnamic acid, either by means of an ammonia lyase-type reaction or by means of a three step route via phenylpyruvate and phenyllactate. The wider significance of such conversions is discussed with similar metabolism of tryptophan and subsequent glycine conjugation potentially explaining the origin of trans-indolylacryloylglycine, a postulated marker for autism. PMID- 22306195 TI - Genetic and functional analysis of the gene encoding neurogranin in schizophrenia. AB - OBJECTIVES: Schizophrenia is a highly heritable disorder, but many aspects of its etiology and pathophysiology remain poorly understood. Recently, a SNP rs12807809 located upstream of the neurogranin (NRGN) gene achieved genome-wide significance in this disorder. METHODS: In order to find the causal variants of NRGN gene in schizophrenia, we searched for genetic variants in the promoter region and all the exons (including both UTR ends and rs12807809) using direct sequencing in a sample of patients with schizophrenia (n=346) and non-psychotic controls (n=345), both being Han Chinese from Taiwan, and conducted an association and functional study. RESULTS: We identified 7 common polymorphisms in the NRGN gene. SNP and haplotype-based analyses displayed no associations with schizophrenia. Additionally, we identified 5 rare variants in 6 out of 346 patients, including 3 rare variants located at the promoter region (g.-620A>G, g.-578C>G, and g. 344G>A) and 2 rare variants located at 5' UTR (c.-74C>G, and c.-41G>A). No rare variants were found in the control subjects. The results of the reporter gene assay demonstrated that the regulatory activity of construct containing g.-620G, g.-578G, g.-344A, c.-74G, and c.-41A was significantly lower as compared to the wild type construct (P<0.01 for g.-578G; P<0.001 for the other constructs). In silico analysis also demonstrated their influences on the regulatory function of NRGN gene. CONCLUSIONS: Our study lends support to the hypothesis of multiple rare mutations in schizophrenia, and provides genetic clues that indicate the involvement of NRGN in this disorder. PMID- 22306196 TI - Neural correlates of the core facets of empathy in schizophrenia. AB - Empathy is a multidimensional construct composed of several components such as emotion recognition, emotional perspective taking and affective responsiveness. Even though patients with schizophrenia demonstrate deficits in all core components of this basic social ability, the neural underpinnings of these dysfunctions are less clear. Using fMRI, we analyzed data from 15 patients meeting the DSM-IV criteria for schizophrenia and 15 matched healthy volunteers performing three separate paradigms tapping the core components of empathy, i.e. emotion recognition, perspective taking and affective responsiveness. Behavioral data analysis indicated a significant empathic deficit in patients, reflected in worse performance in all three domains. Analysis of functional data revealed hypoactivation in a fronto-temporo-parietal network including the amygdala in patients. Moreover, amygdala activation correlated negatively with severity of negative symptoms. The results suggest that schizophrenia patients not only suffer from a broad range of emotional deficits but also show cortical and subcortical abnormalities, extending previous findings on fronto-temporal cortical dysfunctions. Since empathy is related to psychosocial functioning and hence of high clinical relevance in schizophrenia, a more detailed understanding of the exact nature of these impairments is mandatory. PMID- 22306197 TI - Embryonic stem cell strategies to explore neural crest development in human embryos. AB - Controling embryonic stem cell fate in vitro has been a major challenge in the past decade. Several protocols have been developed to obtain neural crest derivatives in culture, using more or less defined conditions. Here, we present various strategies used to date to obtain neural crest specification and the markers that can be used to identify human neural crest cells. PMID- 22306198 TI - Risk of falls and fractures in older adults using atypical antipsychotic agents: a propensity score-adjusted, retrospective cohort study. AB - BACKGROUND: Atypical antipsychotic agents are extensively prescribed in the elderly to treat various behavioral and psychiatric disorders. Past literature has documented an increased risk of falls and factures with the use of risperidone and olanzapine compared with nonuse. However, none of the studies assessed the comparative safety profiles of atypical agents with respect to falls and fractures. OBJECTIVE: The goal of this study was to evaluate the risk of falls and fractures associated with the use of risperidone, olanzapine, and quetiapine in community-dwelling adults aged >=50 years. METHODS: The study involved a propensity score-adjusted approach in new users of risperidone, olanzapine, or quetiapine anytime between July 1, 2000, and June 30, 2008, using data from the IMS LifeLink Health Plan Claims database. Patients were followed up until a hospitalization/emergency department visit for fall/fracture or the end of the study period, whichever occurred earlier. The Cox proportional hazards regression model was used to evaluate the comparative risk of falls/fractures. The covariates in the final model included propensity scores and their interaction terms. RESULTS: There were 12,145 new users of atypical agents in the study population (5083 risperidone, 4377 olanzapine, and 2685 quetiapine). A total of 417 cases of falls/fractures with at least 1 hospitalization/ emergency department visit after the use of the antipsychotic agents were identified. The number of falls for risperidone, olanzapine, and quetiapine were 179 (3.56%), 123 (2.84%), and 115 (4.34%), respectively. After adjusting for propensity scores, the Cox proportional hazards model showed that there was no statistically significant difference with use of risperidone (hazard ratio = 1.10 [95% CI, 0.86 1.39]) or quetiapine (hazard ratio = 1.12 [95% CI, 0.86-1.46]) compared with olanzapine (reference group) in the risk of falls or fractures. CONCLUSIONS: The study found no significant difference across the individual atypical agents in the risk of falls/fractures in community-dwelling older adults. Future studies are required to evaluate the overall safety profiles of the antipsychotic agents in this population. PMID- 22306199 TI - Auditory discrimination training rescues developmentally degraded directional selectivity and restores mature expression of GABA(A) and AMPA receptor subunits in rat auditory cortex. AB - Auditory frequency discrimination training can remediate deteriorated frequency representations and temporal information processing in the adult primary auditory cortex induced by early post-natal pulsed noise exposure. In this study, we investigated the neural mechanisms underlying the restoration of directional selectivity by auditory spatial discrimination training. Rats exposed to pulsed noise during a post-natal critical period demonstrated reduced auditory directional selectivity but could be successfully trained to identify a target sound stimulus at a specific azimuth angle using a reward-contingent auditory discrimination task (EXP rats). In contrast, rats passively exposed to the training procedure but no reward for correct identification of the azimuth angle (PNR rats) showed no improvement and behavioral performance remained significantly below EXP rats and control (CON) rats reared under a normal sonic environment. The expression levels of GABA(A) receptor subunits alpha1, alpha3, beta2, and beta3, and the AMPA GluR2 subunit were significantly altered in the auditory cortex of untrained noise-raised (NR and PNR) rats compared to age matched CON rats, while trained noise-raised (EXP) rats exhibited levels of expression not significantly different from CON rats. Thus, reward-contingent sound-azimuth discrimination training may remediate directional selectivity by restoring the proper expression profile of neurotransmitter receptor subunits in the auditory cortex, allowing for normal spatial selectivity by cortical neurons. The development of auditory directional selectivity depends on the regulated expression of these excitatory and inhibitory neurotransmitter receptor subunits; early pulsed noise may disrupt the normal development of directional selectivity by interfering with receptor expression. PMID- 22306200 TI - Blocking mTORC1 activity by rapamycin leads to impairment of spatial memory retrieval but not acquisition in C57BL/6J mice. AB - Although the involvement of the mTOR (mammalian target of rapamycin) system in memory processes has been reported, information on the effect of rapamycin on spatial learning and memory is limited. It was therefore the aim of the study to show the effect of parenteral rapamycin administration to C57BL/6J mice on performance in the multiple T-maze (MTM) and to determine hippocampal mTOR activity. Rapamycin-treated and -untreated/trained/probed mice are the main part of the experiment considering retrieval and acquisition or consolidation of spatial memory. Six hours following euthanasia hippocampi were extirpated and used for evaluation of mTOR activity as represented by hippocampal levels of S6 protein and its phosphorylated active form (phospho S6 protein, S240,244), a read out of mTOR complex 1 activity. Mice given i.p. rapamycin learned the task of the MTM but failed at the probe trial, showing absence of the phosphorylated active form of S6 protein, indicating inhibition of mTOR activity. Herein, impairing effects of rapamycin on retrieval but not on acquisition or consolidation of spatial memory are shown. Deficient memory retrieval was paralleled by inhibition of mTOR complex 1 activity. The current study extends knowledge on rapamycin in memory mechanisms and challenges work on deeper insights into the role of mTOR in different phases of memory formation and retrieval. PMID- 22306201 TI - RNA modifications by oxidation: a novel disease mechanism? AB - The past decade has provided exciting insights into a novel class of central (small) RNA molecules intimately involved in gene regulation. Only a small percentage of our DNA is translated into proteins by mRNA, yet 80% or more of the DNA is transcribed into RNA, and this RNA has been found to encompass various classes of novel regulatory RNAs, including, e.g., microRNAs. It is well known that DNA is constantly oxidized and repaired by complex genome maintenance mechanisms. Analogously, RNA also undergoes significant oxidation, and there are now convincing data suggesting that oxidation, and the consequent loss of integrity of RNA, is a mechanism for disease development. Oxidized RNA is found in a large variety of diseases, and interest has been especially devoted to degenerative brain diseases such as Alzheimer disease, in which up to 50-70% of specific mRNA molecules are reported oxidized, whereas other RNA molecules show virtually no oxidation. The iron-storage disease hemochromatosis exhibits the most prominent general increase in RNA oxidation ever observed. Oxidation of RNA primarily leads to strand breaks and to oxidative base modifications. Oxidized mRNA is recognized by the ribosomes, but the oxidation results in ribosomal stalling and dysfunction, followed by decreased levels of functional protein as well as the production of truncated proteins that do not undergo proper folding and may result in protein aggregation within the cell. Ribosomal dysfunction may also signal apoptosis by p53-independent pathways. There are very few reports on interventions that reduce RNA oxidation, one interesting observation being a reduction in RNA oxidation by ingestion of raw olive oil. High urinary excretion of 8-oxo-guanosine, a biomarker for RNA oxidation, is highly predictive of death in newly diagnosed type 2 diabetics; this demonstrates the clinical relevance of RNA oxidation. Taken collectively the available data suggest that RNA oxidation is a contributing factor in several diseases such as diabetes, hemochromatosis, heart failure, and beta-cell destruction. The mechanism involves free iron and hydrogen peroxide from mitochondrial dysfunction that together lead to RNA oxidation that in turn gives rise to truncated proteins that may cause aggregation. Thus RNA oxidation may well be an important novel contributing mechanism for several diseases. PMID- 22306202 TI - Synthetic membrane active amphiphiles. AB - During the past several decades, various synthetic organic compounds that form pores in bilayer membranes have been prepared and studied. These membrane active amphiphiles have also proved to be useful in affecting the transport of molecules into or through the bilayer. This article discusses the evolution of these compounds and exemplifies recent applications such as enhancement of antimicrobial activity. PMID- 22306203 TI - Prospective evaluation of molecular screening for Lynch syndrome in patients with endometrial cancer <= 70 years. AB - OBJECTIVE: Lynch syndrome (LS) is a hereditary syndrome that predisposes to multiple malignancies including endometrial cancer (EC). We aimed to evaluate a diagnostic strategy for LS based on routine analysis of microsatellite instability (MSI) and immunohistochemical (IHC) staining for mismatch repair (MMR) proteins in tumour tissue of all newly diagnosed EC patients <= 70 years. METHODS: Consecutive EC patients <= 70 years were included prospectively in eight Dutch centres. EC specimens were analysed for MSI, IHC of four MMR proteins, MMR gene methylation status and BRAF-mutations. tumours were classified as; 1) likely to be caused by LS, 2) sporadic MSI-H, or 3) microsatellite stable (MSS). RESULTS: Tumour specimens of 179 patients (median age 61 years, IQR 57-66) were analysed. In our study 92% of included patients were over 50 years of age. Eleven EC patients were found likely to have LS (6%; 95% CI 3-11%), including 1 patient suspected of an MLH1, 2 of an MSH2, 6 of an MSH6 and 2 of a PMS2 gene defect. Germline mutation analyses revealed 7 MMR gene germline mutations. Ten patients likely to have LS (92%) were older than 50 years. In addition, 31 sporadic MSI-H tumours with MLH1 promoter hypermethylation (17%; 95% CI 13-24%) were identified. CONCLUSIONS: Molecular screening for LS in patients with EC diagnosed <= 70 years, leads to identification of a profile likely to have LS in 6% of cases. New screening guidelines for LS are needed, including recommendations for EC patients older than 50 years of age. PMID- 22306204 TI - Myxoma virus-mediated oncolysis of ascites-derived human ovarian cancer cells and spheroids is impacted by differential AKT activity. AB - OBJECTIVE: We propose that metastatic epithelial ovarian cancer (EOC) is a potential therapeutic target for the oncolytic agent, Myxoma virus (MYXV). METHODS: Primary EOC cells were isolated from patient ascites and cultured as adherent cells or in suspension using Ultra Low-Attachment dishes. MYXV expressing green fluorescent protein was used to infect cells and spheroids. Infection was monitored by fluorescence microscopy, viral titering and immunoblotting for M-T7 and M130 virus protein expression, and cell viability by alamarBlue assay. Akti-1/2 (5 MUM) and rapamycin (20 nM) were used to assay the role of PI3K-AKT signaling in mediating MYXV infection. RESULTS: Ascites-derived EOC cells grown in adherent culture are effectively killed by MYXV infection. EOC cells grown in suspension to form three-dimensional EOC spheroids readily permit MYXV entry into cells, yet are protected from the cytopathic effects of late MYXV infection. Upon reattachment (to model secondary metastasis), EOC spheroids are re-sensitized to MYXV-mediated oncolysis. The critical determinant that facilitates efficient MYXV infection is the presence of an activated PI3K-AKT signaling pathway. Treatment with the specific AKT inhibitor Akti-1/2 reduces infection of monolayer EOC cells and spheroids. Direct infection of freshly collected ascites demonstrated that 54.5% of patient samples were sensitive to MYXV-mediated oncolytic cell killing. We also demonstrate that factor(s) present in ascites may negatively impact MYXV infection and oncolysis of EOC cells, which may be due to a down-regulation in endogenous AKT activity. CONCLUSIONS: Differential activity of AKT serves as the mechanistic basis for regulating MYXV mediated oncolysis of EOC spheroids during key steps of the metastatic program. In addition, we provide the first evidence that MYXV oncolytic therapy may be efficacious for a significant proportion of ovarian cancer patients with metastatic disease. PMID- 22306205 TI - Glia determine the course of brain-derived neurotrophic factor-mediated dendritogenesis and provide a soluble inhibitory cue to dendritic growth in the brainstem. AB - Cardiorespiratory control neurons in the brainstem nucleus tractus solitarius (NTS) undergo dramatic expansion of dendritic arbors during the early postnatal period, when functional remodeling takes place within the NTS circuitry. However, the underlying molecular mechanisms of morphological maturation of NTS neurons are largely unknown. Our previous studies point to the neurotrophin brain-derived neurotrophic factor (BDNF), which is abundantly expressed by NTS-projecting primary sensory neurons, as a candidate mediator of NTS dendritogenesis. In the current study, we used neonatal rat NTS neurons in vitro to examine the role of BDNF in the dendritic development of neurochemically identified subpopulations of NTS neurons. In the presence of abundant glia, BDNF promoted NTS dendritic outgrowth and complexity, with the magnitude of the BDNF effect dependent on neuronal phenotype. Surprisingly, BDNF switched from promoting to inhibiting NTS dendritogenesis upon glia depletion. Moreover, glia depletion alone led to a significant increase in NTS dendritic outgrowth. Consistent with this result, astrocyte-conditioned medium (ACM), which promoted hippocampal dendritogenesis, inhibited dendritic growth of NTS neurons. The latter effect was abolished by heat-inactivation of ACM, pointing to a diffusible astrocyte-derived negative regulator of NTS dendritic growth. Together, these data demonstrate a role for BDNF in the postnatal development of NTS neurons, and reveal novel effects of glia on this process. Moreover, previously documented dramatic increases in NTS glial proliferation in victims of sudden infant death syndrome (SIDS) underscore the importance of our findings and the need to better understand the role of glia and their interactions with BDNF during NTS circuit maturation. Furthermore, while it has previously been demonstrated that the specific effects of BDNF on dendritic growth are context-dependent, the role of glia in this process is unknown. Thus, our data carry important implications for mechanisms of dendritogenesis likely beyond the NTS. PMID- 22306206 TI - Perspectives of Australian adults about protecting the privacy of their health information in statistical databases. AB - OBJECTIVES: The aim of this study was to discover the public's attitude and views towards privacy in health care. This is a part of a larger project which aims to gain an insight into what kind of privacy is needed and develop technical measures to provide such privacy. METHODS: The study was a two-stage process which combined qualitative and quantitative research. Stage One of the study comprised arranging and facilitating focus groups while in Stage Two we conducted a social survey. MEASUREMENTS: We measured attitudes towards privacy, medical research and consent; privacy concern about sharing one's health information for research; privacy concern about the possibility that some specific information from medical records could be linked to the patient's name in a situation that was not related to medical treatment. RESULTS: The results of the study revealed both great support for medical research (98%), and concern about privacy of health information (66%). Participants prefer to be asked for their permission before their health information is used for any purpose other than medical treatment (92%), and they would like to know the organisation and details of the research before allowing the use of their health records (83%). Age, level of education, place of birth and employment status are most strongly associated with privacy concerns. The study showed that there are some particularly sensitive issues and there is a concern (42-60%) about any possibility of linking these kinds of data to the patient's name in a situation that is not related to medical treatment. Such issues include sexually transmitted diseases, abortions and infertility, family medical history/genetic disorders, mental illness, drug/alcohol related incidents, lists of previous operations/procedures/dates and current medications. CONCLUSIONS: Participants believe they should be asked for permission before their health information is used for any purpose other than medical treatment. However, consent and privacy concerns are not necessary related. Assuring individuals that their personal health information is de identified reduces their concern about the necessity of consent for releasing health information for research purposes, but many people are not aware that removing their names and other direct identifiers from medical records does not guarantee full privacy protection for their health information. Privacy concerns decrease as extra security measures are introduced to protect privacy. Therefore, instead of "tailoring concern" as proposed by Willison we suggest improving privacy protection of personal information by introducing additional security measures in data publishing. PMID- 22306207 TI - Carbamazepine-induced thrombocytopenia. PMID- 22306208 TI - Role of zebrafish thrombocyte and non-thrombocyte microparticles in hemostasis. AB - Hemostasis is a defense mechanism that protects an organism from bleeding in the event of injury. We have previously demonstrated the utility of the zebrafish as a model to study human hemostasis. However, there are no studies on the role of microparticles in hemostasis in early vertebrates. Studying microparticles in zebrafish may provide insight into the evolution of microparticle function in hemostasis and may lead to direct observation of these microparticles in zebrafish larvae due to transparency of the vessels. In this investigation we demonstrate the presence of cellular microparticles in fish blood by both immunostaining as well as by using zebrafish whose thrombocytes are labeled with green fluorescent protein. Further investigation showed that microparticles were also labeled by fluorescein isothiocyanate annexin V, suggesting that these particles are derived via apoptosis. A portion of the fluorescein isothiocyanate annexin V labeled microparticles was also labeled by DiI-C18. Labeling by DiI-C18 suggests that some microparticles are derived from young thrombocytes. Additionally, GpIIb antibody labels almost all thrombocyte-derived microparticles and a greater percentage of microparticles are labeled by GpIIb antibody than by DiI-C18. This suggests that thrombocyte microparticles are derived from both young and mature thrombocytes. Furthermore, the increase of microparticles by adding excessive microparticles into blood in vitro and through intravenous injections led to an increased hemostatic response. In addition, treatment with tumor necrosis factor alpha resulted in an increased number of thrombocyte microparticles and enhanced hemostasis; in contrast, treatment with zVAD-FMK, a caspase inhibitor, resulted in a decrease in thrombocyte microparticles and decreased hemostasis. We also found that thrombocyte microparticles agglutinate, along with other cells and cellular microparticles, in the presence of an excess of either ristocetin or ultra-large von Willebrand factor. Also, stimulation of von Willebrand factor release in vivo resulted in clusters of thrombocyte microparticles in the veins. Moreover, thrombocyte microparticles were the first to appear at the site of arterial injury. We found that thrombocyte microparticles are functionally equivalent to platelet microparticles. The microparticles initiate arterial thrombus formation in a von Willebrand factor dependent manner and further enhance thrombus formation by forming clusters of microparticles in venous thrombosis. This finding may have applications for understanding the role of platelet microparticles in humans and may have diagnostic applications. PMID- 22306209 TI - Exploring the gap between dynamic and constraint-based models of metabolism. AB - Systems biology provides new approaches for metabolic engineering through the development of models and methods for simulation and optimization of microbial metabolism. Here we explore the relationship between two modeling frameworks in common use namely, dynamic models with kinetic rate laws and constraint-based flux models. We compare and analyze dynamic and constraint-based formulations of the same model of the central carbon metabolism of Escherichia coli. Our results show that, if unconstrained, the space of steady states described by both formulations is the same. However, the imposition of parameter-range constraints can be mapped into kinetically feasible regions of the solution space for the dynamic formulation that is not readily transferable to the constraint-based formulation. Therefore, with partial kinetic parameter knowledge, dynamic models can be used to generate constraints that reduce the solution space below that identified by constraint-based models, eliminating infeasible solutions and increasing the accuracy of simulation and optimization methods. PMID- 22306210 TI - Utility of pulmonary hypertension for the prediction of heart failure following acute myocardial infarction. AB - Pulmonary hypertension (PH) is usually perceived as a complication of established heart failure (HF) rather than as a predictor of HF or a marker of subclinical HF. PH may develop because of cardiac alterations that result in increased filling pressures after acute myocardial infarction (AMI). We hypothesized that PH might be a useful marker to predict the risk of HF after AMI. We studied 1,054 patients with AMI. Pulmonary artery systolic pressure (PASP) was estimated using echocardiography at the index admission and PH was defined as a PASP >35 mm Hg. The primary end point was readmission for HF at 1 year. PH was present in 471 patients (44.6%) and was strongly associated with age, decreased ejection fraction, advanced diastolic dysfunction, and moderate/severe mitral regurgitation (p <0.0001 for all comparisons). Area under the receiver operating characteristic curve was significantly higher for estimated PASP (0.74 +/- 0.02) compared to other echocardiographic parameters (p = 0.02 to 0.0003). After adjustments for clinical and echocardiographic variables in a Cox model, PH was associated with a hazard ratio of 3.10 for HF (95% confidence interval 1.31 to 2.57, p <0.0001). After adding estimated PASP to a model containing clinical and echocardiographic risk factors, net reclassification improvement was 0.21 (95% confidence interval 0.11 to 0.31, p <0.0001). In conclusion, PASP integrates the severity of multiple hemodynamic determinants of increased left atrial pressures that lead to an increase in pulmonary venous pressure. In AMI, PH at the index admission is a useful marker in unmasking latent subclinical HF and predicting the development of overt HF. PMID- 22306211 TI - Two cases of myxoma of the external auditory canal. AB - Myxomas were found in the outer ear canal of a 66-year-old female and a 51-year old male. Both tumors were soft and sessile and located at the antero-superior part of the external auditory canal near the eardrum. Profuse, clear mucus was seen when the tumor ruptured or was incised. Histology showed spindle-shaped and stellate cells in myxoid extracellular matrix. CT images revealed a small bone defect adjacent to the tumor in the meatal bone. This bony defect was confirmed during surgery. The bony defects seen in both cases may have something to do with the genesis of the tumor. We found only 5 sporadic cases, including ours, reported in the English literature. As myxoma of the outer ear canal is also reported in 18 patients as a symptom of Carney's complex, we must check for accompanying symptoms of the complex such as spotty skin pigmentation, endocrine tumors, or schwannoma. Total removal of the tumor is necessary to prevent recurrence. PMID- 22306212 TI - The effect of hip adduction angle on patellar position measured using real time ultrasound scanning. AB - INTRODUCTION: There are limited in vivo studies investigating the influence of the Iliotibial Band (ITB) on patellar position, despite numerous references in the literature to this relationship. The purpose of this study was to investigate how the ITB influences patellar position, in vivo, indirectly through alteration of frontal plane hip position. METHOD: Twelve healthy, asymptomatic, male subjects (age 23 +/- 2.6 years) had their patellar position examined using real time ultrasound scanning. The knee was passively placed into 20 degrees flexion and combined with hip neutral, 20 degrees hip adduction and 20 degrees hip abduction. Mean patellar position (distance from the lateral border of the patella to the edge of the intersection of the trochlear groove and lateral femoral condyle) was measured, with the smaller values representing a position whereby the patella is drawn more laterally and closer to the lateral femoral condyle. RESULTS: Mean patellar position for neutral was 8.1mm (+/- 1.72 mm). Following 20 degrees hip abduction the mean patellar position was 8.9 mm (+/- 1.7 9 mm), this was a statistically significant change in patellar position (p=0.003). Following 20 degrees hip adduction the mean patellar displacement was 7.3mm (+/- 1.4mm) which, again, was a statistically significant change in patellar position (p=0.009). The results indicate that with the hip adduction the patella was positioned significantly more laterally (smaller value for distance). DISCUSSION: The results of this study support the hypothesis that hip adduction which is likely to create loading and lengthening of the ITB causes significantly greater lateral displacement of the patella, than when the hip is abducted and the ITB unloaded. PMID- 22306213 TI - Clinical and echocardiographic outcomes after repair of mitral valve bileaflet prolapse due to myxomatous disease. AB - OBJECTIVE: Repair of mitral regurgitation (MR) due to bileaflet prolapse poses many technical challenges. The late outcomes after repair are also not well characterized in this population. Published series have often included patients with mixed causes of prolapse and/or lack long-term echocardiographic follow-up. Myxomatous disease represents an important cause of bileaflet prolapse and MR and, thus, served as the focus of the present study. METHODS: A total of 142 patients, mean age 60.4 +/- 13.2 years, underwent mitral valve (MV) repair of bileaflet prolapse due to myxomatous disease from 2001 to 2010. Concomitant coronary artery bypass grafting was performed in 16 patients (11%). All patients were followed up by a dedicated MV clinic with a follow-up interval that extended up to 8.6 years. RESULTS: No hospital deaths occurred. Ring annuloplasty was used for all patients. Additional MV repair techniques included chordal transfer in 73, a hybrid-flip-over technique in 23, polytetrafluoroethylene neochords in 26, edge-to-edge repair in 11, and commissuroplasty in 9. Prolapse involving more than 1 posterior leaflet scallop was observed in 103 patients (73%), and prolapse of more than 1 anterior leaflet scallop was observed in 76 (54%). During follow up, 4 patients had MR grade 2+ or greater, and 2 patients required subsequent MV reoperation. The 5-year survival, freedom from recurrent MR (>= 2+), and freedom from MV reoperation was 95.2% +/- 2.8%, 92.6% +/- 3.9%, and 94.0% +/- 4.9%, respectively. CONCLUSIONS: MV repair of bileaflet prolapse due to myxomatous disease is safe and durable. Successful repair often requires a combination of surgical repair techniques. PMID- 22306214 TI - Extending the scope of mitral valve repair in active endocarditis. AB - OBJECTIVE: During the last 2 decades, we have applied a repair-oriented surgical approach to patients with active mitral valve endocarditis. We retrospectively analyzed the long-term outcomes with this repair-oriented approach. METHOD: Between 1991 and 2010, 137 patients underwent operation for active mitral valve endocarditis; of these, 109 patients (80%) had mitral valve repair and represent the study cohort. Repair techniques without patch extension (no-patch techniques) include triangular or quadrangular resection (n = 49), sliding plasty (n = 24), neochordae (n = 18), chordal transfer (n = 12), and others (n = 5). Repair techniques using patch extension (patch techniques) included pericardium (n = 42), tricuspid autograft (n = 8), flip-over technique (n = 7), and partial mitral valve homograft (n = 5). Patches were used in 67 patients (61%). Ring annuloplasty was performed in 60 patients, and a pericardial band was used in 13 patients. Clinical and echocardiographic follow-up were performed. Median follow up was 48 months. RESULTS: Hospital mortality was 16%. At 8 years, overall survival was 62% +/- 10% with no differences between patients with or without patch repair (P = .5). Freedom from mitral valve repair failure was 81% +/- 14% in patients with patch repair and 90% +/- 10% in patients without patch repair (P = .09). The rate of thromboembolic or bleeding event was 1% per patient-year, and the rate of endocarditis recurrence was 0.3% per patient-year. Univariable predictors of mortality were age more than 70 years (P < .0001), perivalvular abscess (P = .002), diabetes mellitus (P = .0002), and renal failure (P = .04). Predictors of repair failure were renal failure (P = .035) and perivalvular abscess (P = .033). CONCLUSIONS: In active mitral valve endocarditis, a repair oriented surgical approach achieves a reparability rate of 80% with acceptable morbidity and good long-term results. The use of patch techniques offers a durability rate that approximates the rate obtained with the no-patch techniques. PMID- 22306215 TI - Effects of institutional volumes on operative outcomes for aortic root replacement in North America. AB - OBJECTIVES: Hospital procedure volume has been strongly associated with postoperative mortality for a number of complex cardiovascular procedures. Although not yet described, a similar relationship might be expected for surgical procedures involving the aortic root and/or ascending aorta. The present study sought to evaluate the relationship between the volume of aortic root replacement procedures and the operative results for centers in North America. METHODS: Patient-level data for 13,358 elective aortic root and aortic valve-ascending aortic procedures performed from 2004 through 2007 were obtained from 741 North American hospitals participating in the Society of Thoracic Surgeons Adult Cardiac Surgery Database. Marginal logistic regression modeling was used for risk adjustment. The hospital procedure volume was the primary predictor variable. Patient demographics, comorbid conditions, and operative characteristics were included as the predictor variables for risk adjustment. The primary outcome measures included unadjusted operative mortality and adjusted odds ratio for mortality. RESULTS: The preoperative patient risk profiles were similar at all center volume levels, and the overall unadjusted operative mortality was 4.5%. The unadjusted operative mortality increased with decreasing case volume, from 3.4% in the highest volume centers to 5.8% in the lowest volume centers. Whether hospital volume was assessed as a categorical or continuous variable, its relationship with the adjusted odds ratio for mortality was nonlinear. A negative association was seen between the hospital procedural volume and adjusted odds ratio for mortality (P < .001) that was most pronounced among hospitals performing fewer than 30 to 40 procedures annually. CONCLUSIONS: Patients undergoing elective aortic root or combined aortic valve-ascending aortic surgery at North American hospitals that performed fewer than 30 to 40 of such procedures annually have greater risk-adjusted mortality than those undergoing surgery in higher volume hospitals. Causative factors for this inverse association between hospital volume and mortality deserve additional analysis. PMID- 22306216 TI - Perioperative atrial tachycardia is associated with increased mortality in infants undergoing cardiac surgery. AB - OBJECTIVE: Few data are available on the frequency or importance of perioperative atrial tachycardia in infants. We hypothesized that atrial tachycardia in infants undergoing cardiac surgery is not rare and is associated with increased morbidity and mortality. METHODS: From 2007 through 2010, 777 infants (median age, 1.8 months; interquartile range, 0.33-5.73) underwent cardiac surgery. Their medical records were reviewed for atrial tachycardia during the perioperative period. RESULTS: Of the 777 patients, 64 (8.2%) developed atrial tachycardia. The independent risk factors for developing atrial tachycardia included surgical age 6 months or younger (odds ratio, 4.4; 95% confidence interval, 1.1-19.15), use of 3 or more inotropes (odds ratio, 2.9; 95% confidence interval, 1.4-6.2), and heterotaxy syndrome (odds ratio, 2.9; 95% confidence interval, 1.1-7.4). All cause mortality in the atrial tachycardia group was increased (21.9% vs 7.2%, P<.001) during a median follow-up period of 14.6 months (interquartile range, 6.8 24.6), and atrial tachycardia was independently associated with decreased survival (hazard ratio, 1.9; 95% confidence interval, 1.1-3.8). Infants with perioperative atrial tachycardia had a longer hospital length of stay (32 vs 17 days, P<.001) and duration of inotrope use (10.5 vs 3.0 days, P<.001). A total of 57 patients received antiarrhythmic therapy, with propranolol the most common (n=31). Among the survivors, 48 patients received outpatient antiarrhythmic therapy, which was successfully discontinued in 23 patients at a median duration of 14 months (interquartile range, 5.7-18.6) without recurrence. CONCLUSIONS: Atrial tachycardia is common in infants undergoing cardiac surgery and is independently associated with decreased survival. Among survivors, antiarrhythmic agents successfully controlled atrial tachycardia in most patients with a low recurrence risk after discontinuation. PMID- 22306217 TI - A novel detachable filter to prevent thromboembolism during endovascular surgery. AB - OBJECTIVE: Thromboembolism remains a serious complication during endovascular surgery. Commercially available filter devices, which are unified with the stenting systems, provide short-time performance owing to the adhesion of thrombus to the filters themselves. We have, therefore, developed a new detachable filter that can be used in all major aortic branches and shows greater longevity. The present study assessed the efficacy of the new detachable filter and examined the feasibility of deploying and retrieving the filters. METHODS: We first performed in vitro studies. Our experimental flow model used silicon tubing to simulate the aortic branches. Polystyrene-divinylbenzene microspheres (100 and 200 MUm in diameter), which simulated embolic particles, were injected into the tubing after the detachable filter was deployed. The capture efficacy (number of microspheres trapped in the detachable filter/total injected microspheres) was calculated. In the in vivo studies, the detachable filters were implanted into the carotid, visceral, and renal arteries of 5 mongrel dogs. Angiography was performed every 30 minutes. At 5 hours after implantation, each detachable filter was retrieved by a gooseneck snare catheter. RESULTS: In the in vitro studies, our detachable filters showed high capture efficacy, capturing 99.2% of the 100 MUm microspheres and 99.4% of the 200-MUm microspheres. In the in vivo studies, all detachable filters were successfully deployed into the major branches. Each angiographic study revealed smooth flow without any embolic obstruction of the filter. At 5 hours after deployment, all devices were completely retrieved by the snare catheter without aortic injury. CONCLUSIONS: The new detachable filter showed high efficacy in capturing the particles. All detachable filters were successfully deployed for 5 hours, and the filters were retrieved from the aortic branches without any complications. This novel detachable filter can help prevent serious distal thromboembolism during endovascular surgery. PMID- 22306218 TI - Robotically assisted mitral valve replacement. AB - OBJECTIVE: In the present study, we determined the safety and efficacy of robotic mitral valve replacement using robotic technology. METHODS: From January 2007 through March 2011, more than 400 patients underwent various types of robotic cardiac surgery in our department. Of these, 22 consecutive patients underwent robotically assisted mitral valve replacement. Of the 22 patients with isolated rheumatic mitral valve stenosis (9 men and 13 women), the mean age was 44.7 +/- 19.8 years (range, 32-65). Preoperatively, all patients underwent a complete workup, including coronary angiography and transthoracic echocardiography. Of the 22 patients, 15 had concomitant atrial fibrillation. The surgical approach was through 4 right-side chest ports with femoral perfusion. Aortic occlusion was performed with a Chitwood crossclamp, and antegrade cardioplegia was administered directly by way of the anterior chest. Using 3 port incisions in the right side of the chest and a 2.5- to 3.0-cm working port, all the procedures were completed with the da Vinci S robot. RESULTS: All patients underwent successful robotic surgery. Of the 22 patients, 16 received a mechanical valve and 6 a tissue valve. The mean cardiopulmonary bypass time and aortic crossclamp time was 137.1 +/- 21.9 minutes (range, 105-168) and 99.3 +/- 17.9 minutes (range, 80-133), respectively. No operative deaths, stroke, or other complications occurred, and no incisional conversions were required. After surgery, all the patients were followed up echocardiographically. CONCLUSIONS: Robotically assisted mitral valve replacement can be performed safely in patients with isolated mitral valve stenosis, and surgical results are excellent. PMID- 22306219 TI - Bilateral internal thoracic artery grafting is superior to other forms of multiple arterial grafting in providing survival benefit after coronary bypass surgery. AB - OBJECTIVE: The objective of this study was to examine the effect of arterial grafting on long-term coronary artery bypass grafting mortality. METHODS: Consecutive coronary artery bypass grafting surgeries performed at a single tertiary care center between 1995 and 2007 were reviewed. Long-term survival was compared among patients according to the type of arterial grafts used: no internal thoracic artery, single internal thoracic artery, single internal thoracic artery with other arterial graft, or bilateral internal thoracic artery. Cox proportional hazard models were generated to examine the association of arterial grafting with mortality. RESULTS: A total of 8264 isolated coronary artery bypass grafting operations were performed and followed for a median time of 4.7 years (interquartile range, 2.1-7.5). A single internal thoracic artery was used in the majority of patients (79%), multiple arterial grafts were used in 24% of patients, and bilateral internal thoracic artery grafts were used in 13% of patients. Patients who received multiple arterial grafts were more likely to be younger, to be male, and to undergo non-urgent surgery. After adjusting for these differences, patients who received bilateral internal thoracic artery grafts were found to have a significant survival advantage when compared with all other patients, including those who received a single internal thoracic artery plus other arterial grafts (hazard ratio, 0.818; confidence interval, 0.672 0.996). Survival at 10 years was 71% for patients with bilateral internal thoracic artery grafts compared with 66% for patients with single internal thoracic artery grafts and 58% for patients with no internal thoracic artery graft. Patients with bilateral internal thoracic artery grafts had significantly better freedom from readmission for acute coronary syndrome (hazard ratio, 0.802; confidence interval, 0.668-0.963). CONCLUSIONS: After adjusting for relevant clinical differences, only multiple arterial grafting using the bilateral internal thoracic artery was able to offer a long-term survival advantage over single internal thoracic artery grafting in patients undergoing coronary artery bypass grafting. PMID- 22306220 TI - Effect of granulocyte-colony stimulating factor on expression of selected proteins involved in regulation of apoptosis in the brain of newborn piglets after cardiopulmonary bypass and deep hypothermic circulatory arrest. AB - OBJECTIVE: The study objective was to investigate the effect of granulocyte colony stimulating factor on the expression of proteins that regulate apoptosis in newborn piglet brain after cardiopulmonary bypass and deep hypothermic circulatory arrest. METHODS: The newborn piglets were assigned to 3 groups: (1) deep hypothermic circulatory arrest (30 minutes of deep hypothermic circulatory arrest, 1 hour of low-flow cardiopulmonary bypass); (2) deep hypothermic circulatory arrest with prior injection of granulocyte-colony stimulating factor (17 MUg/kg 2 hours before cardiopulmonary bypass); and (3) sham-operated. After 2 hours of post-bypass recovery, the frontal cortex, striatum, and hippocampus were dissected. The expression of proteins was measured by gel electrophoresis or protein arrays. Data are presented in arbitrary units. Statistical analysis was performed using 1-way analysis of variance. RESULTS: In the frontal cortex, only Fas ligand expression was significantly lower in the granulocyte-colony stimulating factor group when compared with the deep hypothermic circulatory arrest group. In the hippocampus, granulocyte-colony stimulating factor increased Bcl-2 (54.3 +/- 6.4 vs 32.3 +/- 2.2, P = .001) and serine/threonine-specific protein kinase (141.4 +/- 19 vs 95.9 +/- 21.1, P = .047) when compared with deep hypothermic circulatory arrest group. Caspase-3, Bax, Fas, Fas ligand, death receptor 6, and Janus protein tyrosine kinase 2 levels were unchanged. The Bcl 2/Bax ratio was 0.33 for deep hypothermic circulatory arrest group and 0.93 for the granulocyte-colony stimulating factor group (P = .02). In the striatum, when compared with the deep hypothermic circulatory arrest group, the granulocyte colony stimulating factor group had higher levels of Bcl-2 (50.3 +/- 7.4 vs 31.8 +/- 3.8, P = .01), serine/threonine-specific protein kinase (132.7 +/- 12.3 vs 14 +/- 1.34, P = 2.3 * 10(6)), and Janus protein tyrosine kinase 2 (126 +/- 17.4 vs 77.9 +/- 13.6, P = .011), and lower levels of caspase-3 (12.8 +/- 5.0 vs 32.2 +/- 11.5, P = .033), Fas (390 +/- 31 vs 581 +/- 74, P = .038), Fas ligand (20.5 +/- 11.5 vs 57.8 +/- 15.6, P = .04), and death receptor 6 (57.4 +/- 4.4 vs 108.8 +/- 13.4, P = .007). The Bcl-2/Bax ratio was 0.25 for deep hypothermic circulatory arrest and 0.44 for the granulocyte-colony stimulating factor groups (P = .046). CONCLUSIONS: In the piglet model of hypoxic brain injury, granulocyte-colony stimulating factor decreases proapoptotic signaling, particularly in the striatum. PMID- 22306221 TI - Iatrogenic left internal thoracic artery to left subclavian vein fistula after excimer laser pacemaker lead extraction. PMID- 22306222 TI - Left ventricular apical papillary fibroelastoma. PMID- 22306224 TI - Outcome of patients with pulmonary arterial hypertension referred for lung transplantation: a 14-year single-center experience. AB - OBJECTIVE: To analyze the outcomes of patients with pulmonary arterial hypertension referred for lung transplantation and determine the changes over time. METHODS: All patients with pulmonary arterial hypertension referred for lung transplantation in our program from January 1997 to September 2010 were reviewed. Pulmonary arterial hypertension was classified as idiopathic (n = 123) or associated with congenital heart disease (n = 77), connective tissue disease (n = 102), or chronic thromboembolic disease (n = 14). RESULTS: After completing their assessment, 61 patients (19%) were found to be unsuitable for lung transplantation, 38 (12%) refused lung transplantation, 65 (21%) were too early to be listed, and 48 (15%) died before their assessment (n = 34) or being listed (n = 14). Of the 100 patients listed for lung transplantation, 57 underwent bilateral lung transplantation, 22 underwent heart-lung transplantation, 18 died while waiting, and 3 were still waiting. The waiting list mortality was the greatest for patients with connective tissue disease-pulmonary arterial hypertension (34% vs 11% in the remaining patients, P = .005). The number of patients admitted to the hospital to be bridged to lung transplantation increased from 7% in the 1997-2004 cohort to 25% in the 2005-2010 cohort (P = .02). After lung transplantation, the 30-day mortality decreased from 24% in the 1997-2004 group to 6% in the 2005-2010 group (P = .007). The 10-year survival was worse for those with idiopathic pulmonary arterial hypertension (42% vs 70% for the remaining patients, P = .01). The long-term survival reached 69% at 10 years in the patients with connective tissue disease pulmonary arterial hypertension. CONCLUSIONS: Lung transplantation is an option for about one third of the patients with pulmonary arterial hypertension referred for lung transplantation. The 30-day mortality after lung transplantation improved significantly over time, but the long-term survival remained similar between the two cohorts. Patients with connective tissue disease-pulmonary arterial hypertension have a high mortality on the waiting list but excellent long-term survival. PMID- 22306225 TI - Endothelial preservation of the minimally manipulated saphenous vein composite graft: histologic and immunohistochemical study. AB - OBJECTIVE: We evaluated the efficacy of minimally manipulative surgical strategies to harvest the saphenous vein for use in a Y-composite graft based on the left internal thoracic artery in terms of preservation of endothelial structure and function. METHODS: Twenty patients who underwent off-pump coronary revascularization using the saphenous vein in a Y-composite graft based on the left internal thoracic artery were studied. The saphenous vein was harvested from each patient with minimal manipulation. An excess saphenous vein segment was removed before dilatation (control group), and a second segment was removed after dilation performed using a pressure-sensing syringe (conventional group). A third segment was obtained from a Y-composite vein graft dilated by flow and pressure from the left internal thoracic artery (composite group). Hematoxylin-eosin staining and immunohistochemistry using antibodies against CD31, CD34, von Willebrand factor, and endothelial nitric oxide synthase were performed. A generalized estimating equation was adopted for statistical analysis. RESULTS: Histologic and immunohistochemical studies revealed better endothelial preservation in the composite and control groups than in the conventional group (P < .01 in each). The composite group saphenous vein showed a lower grade of endothelial integrity than the control group saphenous vein based on hematoxylin eosin staining, CD34 immunohistochemistry, and nitric oxide synthase staining (P < .001 in each). CONCLUSIONS: Harvesting of the saphenous vein using minimal manipulation for use in a Y-composite graft based on the left internal thoracic artery preserved endothelial structure and function when compared with manually dilated saphenous vein harvesting. PMID- 22306226 TI - Selective cerebral perfusion for thoracic aortic surgery: association with neurocognitive outcome. AB - OBJECTIVES: Optimal brain protection for aortic arch surgery remains unclear. This prospective study examined neurocognitive outcomes in cardiac and thoracic aortic surgical patients, including a small cohort who underwent selective cerebral perfusion. METHODS: Fifty-seven adult cardiac and thoracic aortic surgical patients underwent preoperative and postoperative neurocognitive testing. Patients were divided into 3 groups. Group 1 patients underwent procedures with cardiopulmonary bypass alone (n = 24), group 2 patients with cardiopulmonary bypass and hypothermic circulatory arrest (n = 23), and group 3 patients with cardiopulmonary bypass, hypothermic circulatory arrest, and anterograde selective cerebral perfusion (n = 10). Changes in 14 neurocognitive test scores and 6 neurocognitive domain scores (Attention, Speed, Language, Memory, Executive Function, and Motor Function) were evaluated. RESULTS: Multiple regression analyses examining the relationships of cardiopulmonary bypass time, hypothermic circulatory arrest time, and selective cerebral perfusion time with change in cognitive test performance revealed that selective cerebral perfusion time (range, 39-83 minutes) was a significant predictor of decline in performance on memory and language tests. Hypothermic circulatory arrest (range, 14-40 minutes) and cardiopulmonary bypass (range, 70-369 minutes) times were unrelated to decline. CONCLUSIONS: Complex thoracic aortic repairs requiring prolonged selective cerebral perfusion were associated with decline in neurocognitive function. It is unclear whether the complexity of the repair necessitating prolonged selective cerebral perfusion or the perfusion technique itself contributed to neurocognitive decline. Prospective multicenter neurocognitive evaluations are necessary to assess the relative merits of current brain protection strategies in thoracic aortic surgery. PMID- 22306227 TI - Metabolic profiles predict adverse events after coronary artery bypass grafting. AB - OBJECTIVE: Clinical models incompletely predict the outcomes after coronary artery bypass grafting. Novel molecular technologies can identify biomarkers to improve risk stratification. We examined whether metabolic profiles can predict adverse events in patients undergoing coronary artery bypass grafting. METHODS: The study population comprised 478 subjects from the CATHGEN biorepository of patients referred for cardiac catheterization who underwent coronary artery bypass grafting after enrollment. Targeted mass spectrometry-based profiling of 69 metabolites was performed in frozen, fasting plasma samples collected before surgery. Principal components analysis and Cox proportional hazards regression modeling were used to assess the relation between the metabolite factor levels and a composite outcome of postcoronary artery bypass grafting myocardial infarction, the need for percutaneous coronary intervention, repeat coronary artery bypass grafting, and death. RESULTS: During a mean follow-up period of 4.3 +/- 2.4 years, 126 subjects (26.4%) experienced an adverse event. Three principal components analysis-derived factors were significantly associated with an adverse outcome on univariate analysis: short-chain dicarboxylacylcarnitines (factor 2, P = .001); ketone-related metabolites (factor 5, P = .02); and short-chain acylcarnitines (factor 6, P = .004). These 3 factors remained independently predictive of an adverse outcome after multivariate adjustment: factor 2 (adjusted hazard ratio, 1.23; 95% confidence interval, 1.10-1.38; P < .001), factor 5 (odds ratio, 1.17; 95% confidence interval, 1.01-1.37; P = .04), and factor 6 (odds ratio, 1.14; 95% confidence interval, 1.02-1.27; P = .03). CONCLUSIONS: Metabolic profiles are independently associated with adverse outcomes after coronary artery bypass grafting. These profiles might represent novel biomarkers of risk that can augment existing tools for risk stratification of coronary artery bypass grafting patients and might elucidate novel biochemical pathways that mediate risk. PMID- 22306228 TI - Occult gastrointestinal bleeding in patients with a left ventricular assist device axial flow pump: diagnostic tools and therapeutic algorithm. PMID- 22306229 TI - Chronology of age-related disease definitions: osteoporosis and sarcopenia. AB - Low muscle mass at older age has been associated with functional impairments, cognitive decline and mortality. The term sarcopenia, coined in 1988, has been used interchangeably to describe low muscle mass, strength, and function. Without a well defined definition, results of studies using the term sarcopenia cannot be compared. Difficulties in defining sarcopenia parallel the history of defining osteoporosis. To understand critical steps that are needed to reach consensus in defining age-related diseases, we have identified milestones in the history of defining osteoporosis and compared these to sarcopenia. As a result, the main missing steps in the process of defining sarcopenia are: specific treatment options, pharmaceutical interest, and public awareness. Similar to osteoporosis being defined as 'low bone mineral density', the term sarcopenia should be reserved for 'low muscle mass'. Consensus must be reached regarding the diagnostic criteria to quantify muscle mass, correction factors, and reference populations used to define cut-off values of muscle mass. PMID- 22306230 TI - The developmental dynamics of behavioral growth processes in rodent egocentric and allocentric space. AB - In this review I focus on how three methodological principles advocated by Philip Teitelbaum influenced my work to this day: that similar principles of organization should be looked for in ontogeny and recovery of function; that the order of emergence of behavioral components provides a view on the organization of that behavior; and that the components of behavior should be exhibited by the animal itself in relatively pure form. I start by showing how these principles influenced our common work on the developmental dynamics of rodent egocentric space, and then proceed to describe how these principles affected my work with Yoav Benjamini and others on the developmental dynamics of rodent allocentric space. We analyze issues traditionally addressed by physiological psychologists with methods borrowed from ethology, EW (Eshkol-Wachman) movement notation, dynamical systems and exploratory data analysis. Then we show how the natural origins of axes embodied by the behavior of the organism itself, are used by us as the origins of axes for the measurement of the developmental moment-by-moment dynamics of behavior. Using this methodology we expose similar principles of organization across situations, species and preparations, provide a developmental view on the organization of behavior, expose the natural components of behavior in relatively pure form, and reveal how low level primitives generate higher level constructs. Advances in tracking technology should allow us to study how movements in egocentric and allocentric spaces interlace. Tracking of multi-limb coordination, progress in online recording of neural activity in freely moving animals, and the unprecedented accumulation of genetically engineered mouse preparations makes the behavioral ground plan exposed in this review essential for a systematic study of the brain/behavior interface. PMID- 22306231 TI - Neuronal aggregates are associated with phenotypic onset in the R6/2 Huntington's disease transgenic mouse. AB - Huntington's disease (HD) is caused by the expansion of the polyglutamine tract expressed in the huntingtin protein. Data from patients show a strong negative correlation between CAG repeat size and age of disease onset. Recent studies in mixed background C57*CBA R6/2 mice suggest the inverse correlation observed in the human disease may not be replicated in some animal models of HD. To further clarify the relationship between repeat length and age of onset, congenic C57BL6/J R6/2 transgenic mice expressing 110, 260 or 310 CAG were tested in a comprehensive behavioral battery at multiple ages. Data confirmed the findings of earlier studies and indicate that on a pure C57BL6/J genetic background, R6/2 mice with larger repeats exhibit a delay in phenotypic onset with increasing polyglutamine size (6 weeks in 110 CAG and 17 weeks in 310 CAG mice). Further analysis confirmed a decrease in transgene transcript expression in 310 CAG mice as well as differential aggregated protein localization in association with repeat length. Mice expressing 110 CAG developed aggregates that localized almost exclusively to the nucleus of neuronal cells in the striatum and cortex. In contrast, tissue from 310 CAG mice exhibited predominantly extranuclear inclusions. Novel mutant protein analysis obtained using time-resolved fluorescence resonance energy transfer (FRET) revealed that soluble protein levels decreased with disease onset in R6/2 mice while aggregated protein levels increased. We believe that these data suggest a role for aggregation and inclusion localization in HD pathogenesis and propose a mechanism for the age of onset delay observed in R6/2 mice. PMID- 22306232 TI - Interpersonal problems as predictors of therapeutic alliance and symptom improvement in cognitive therapy for depression. AB - BACKGROUND: The degree to which interpersonal problems of depressed patients improve over the course of cognitive therapy (CT) and relate to the quality of the therapeutic alliance and to symptom improvement, remains unclear. METHODS: We analyzed data of adult outpatients (N=523) with major depressive disorder participating in a clinical trial to determine the factor structure of the Inventory of Interpersonal Problems-Circumplex (IIP-C) and to relate the observed factor scores to the quality of the therapeutic alliance and symptom improvement over the course of CT. Patients received 16-20 sessions protocol (50-60 min each) of individual CT according to the treatment manual by Beck et al. (1979). RESULTS: We found a three-factor structure (interpersonal distress, agency, and communion) of interpersonal problems. Interpersonal distress decreased (d=.90), but interpersonal style did not change substantively during CT (communion d=.03; agency d=.14). High initial agency scores related negatively to the therapeutic alliance (beta=-.12), whereas high initial communion scores related positively to the therapeutic alliance (beta=.15). Elevated pre-treatment interpersonal distress scores were related to both weaker therapeutic alliances (beta=.13) and higher symptom levels throughout treatment (beta=.10). LIMITATIONS: All patients in this study had recurrent MDD and it is therefore uncertain whether the results would generalize to patients with other psychiatric disorders. CONCLUSIONS: This study supports the use of the IIP-C as a comprehensive measure of patients' interpersonal style and interpersonal distress. The IIP-C measured before CT showed some predictive validity with respect to therapeutic alliance measured at the midpoint and therapy outcome. The clinical importance of these findings is discussed. PMID- 22306233 TI - Deficits in upper limb position sense of children with Spastic Hemiparetic Cerebral Palsy are distance-dependent. AB - This study examined the arm position sense in children with Spastic Hemiparetic Cerebral Palsy (SHCP) and typically developing children (TD) by means of a contralateral matching task. This task required participants to match the position of one arm with the position of the other arm for different target distances and from different starting positions. Results showed that children with SHCP exhibited with both arms larger matching errors than the TD group, but only when the distance between the arms at the start of the movement was large. In addition, the difference in errors between the less-impaired and the impaired limb changed as a function of the distance in the SHCP group whereas no interlimb differences were found in the TD group. Finally, spasticity and restricted range of motion in children with SHCP were not related to the proportion of undershoot and size of absolute error. This suggests that SHCP could be associated with sensory problems in conjunction with their motor problems. In conclusion, the current study showed that accurate matching of the arms is greatly impaired in SHCP when compared to TD children, irrespective of which arm is used. Moreover, this deficit is particularly present for large movement amplitudes. PMID- 22306234 TI - Invasive pneumococcal disease and pandemic (H1N1) 2009, Denver, Colorado, USA. AB - Pneumococcal pneumonia was a complication during previous influenza pandemics but was not evident initially during pandemic (H1N1) 2009. During October 2009 in Denver, Colorado, USA, invasive pneumococcal disease (IPD) and pandemic (H1N1) 2009 peaked simultaneously, which suggests a link. We compared cases of IPD in October 2009 with cases in February 2009, the most recent peak month of seasonal influenza. During October 2009, we observed 58 IPD cases, which was 3* the average number of IPD cases that usually occur in October in Denver. Patients with IPD in October 2009 were younger and more likely to have chronic lung disease than patients who had IPD in February 2009; a total of 10/47 patients had influenza, and 33/53 patients had influenza-like illness. Thus, ~17%-62% cases of IPD may have been associated with pandemic (H1N1) 2009. Pneumococcal disease prevention strategies should be emphasized during future influenza pandemics. PMID- 22306235 TI - Additive anti-inflammatory effects of beta 2 adrenoceptor agonists or glucocorticosteroid with roflumilast in human peripheral blood mononuclear cells. AB - The phosphodiesterase 4 inhibitor (PDE4i) roflumilast has been approved in the US and EU for treatment of GOLD stage 3 and 4 chronic obstructive pulmonary disease (COPD). Inhaled beta2 adrenoceptor agonist bronchodilators and anti-inflammatory glucocorticosteroids are also used as standard of care in COPD. We investigated the anti-inflammatory interaction of roflumilast in combination with long-acting beta2 agonists (LABA), salmeterol or formoterol, or a glucocorticosteroid, dexamethasone, on cytokine production from LPS-stimulated human primary peripheral blood mononuclear cells (PBMC). Salmeterol or formoterol caused a concentration-dependent inhibition of tumor necrosis factor-alpha (TNFalpha) secretion with an IC50 of 0.33 pM (C.I. 0.006-19) and 34 pM (C.I. 13-87), respectively. When roflumilast was evaluated, the addition of salmeterol (1 nM) to roflumilast caused the IC50 for roflumilast to shift from 1.8 nM (C.I. 0.8-4) to 4.1 pM (C.I.0.3-69) (p < 0.01), and maximal inhibition increased from 72.5 +/- 3.2% to 90.9 +/- 3.1%. Addition of formoterol to roflumilast also produced an increased TNFalpha inhibition more than either drug alone (p < 0.05). The inhibition of TNFalpha production with salmeterol was both beta2 adrenoceptor- and protein kinase A-dependent. Addition of roflumilast (10 nM) in the presence of dexamethasone increased the inhibition of LPS-induced TNFalpha and CCL3. Roflumilast in combination with salmeterol, formoterol, or dexamethasone increased the inhibition of LPS-induced TNFalpha from human PBMC, in an additive manner. Addition of roflumilast to either a beta2 adrenoceptor agonist or a glucocorticosteroid may provide superior anti-inflammatory activity and greater efficacy in COPD patients and be dose sparing. PMID- 22306236 TI - 12-h or 8-h shifts? It depends. AB - Since 12-h shifts were first implemented, the question has been asked - are 'twelves' better than 'eights'? People trying to answer this question invariably refer to the limited literature at their disposal, often piecemeal, small-scale studies comparing 8-h versus 12-h shifts in isolated groups of workers in which many other factors vary concurrently. The narrow perspective and sometimes 'vested interests' of the organizations, researchers, publishers and individual workers can influence both the choice of measures, the analysis of results and their interpretation. The current review suggests that it is not sufficient to evaluate a shift pattern on the basis of a single dimension of a working time arrangement, such as shift length. Numerous factors associated with the work practice influence the outcome of a shift pattern including start times, pattern of shifts and amount of overtime. Moreover, the type of work being done and the demographics or characteristics of the workforce are additional mediating factors. Finally, and perhaps most critically, the relative importance assigned to different outcome measures is an important consideration. There are situations where total sleep time might increase following a change to 12-h shifts, whereas domestic life for some workers may deteriorate. Additionally, safety measures may show improvements on 8-h shifts but physical or psychological health outcomes may be worse. The myriad combinations of work pattern, work task, worker and outcome measure under investigation mean that the best way to take account of these complexities may be to use an approach that manages 'system' risk. Given the non linearities in the system, and the fact that current approaches either ignore, or privilege a subset of outcomes, it is perhaps more appropriate to conceptualize working time arrangements as an 'ecosystem' and to address the risks in the overall system as opposed to a single dimension such as shift length. PMID- 22306237 TI - Sleep in special needs children: the challenge. PMID- 22306238 TI - Assessing common classification methods for the identification of abnormal repolarization using indicators of T-wave morphology and QT interval. AB - Various parameters based on QTc and T-wave morphology have been shown to be useful discriminators for drug induced I(Kr)-blocking. Using different classification methods this study compares the potential of these two features for identifying abnormal repolarization on the ECG. A group of healthy volunteers and LQT2 carriers were used to train classification algorithms using measures of T-wave morphology and QTc. The ability to correctly classify a third group of test subjects before and after receiving d,l-sotalol was evaluated using classification rules derived from training. As a single electrocardiographic feature, T-wave morphology separates normal from abnormal repolarization better than QTc. It is further indicated that nonlinear boundaries can provide stronger classifiers than a linear boundaries. Whether this is true in general with other ECG markers and other data sets is uncertain because the approach has not been tested in this setting. PMID- 22306239 TI - Activity of JNJ-Q2, a new fluoroquinolone, tested against contemporary pathogens isolated from patients with community-acquired bacterial pneumonia. AB - JNJ-Q2 is a broad-spectrum fluoroquinolone with bactericidal activity against Gram-positive and Gram-negative pathogens and is currently in clinical development for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin-structure infections. This study determined the activity of JNJ-Q2 against a worldwide year 2010 collection (89 centres in 27 countries) of three common respiratory pathogens (3757 isolates) from patients with CABP. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were tested by the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method, and susceptibility rates for comparators were assessed using CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint criteria. JNJ-Q2 had activity against all three species, with 96.9% of strains inhibited at <=0.015 mg/L. JNJ-Q2 [minimum inhibitory concentration for 50% and 90% of the organisms, respectively (MIC(50/90))=0.008/0.015 mg/L] demonstrated a 16-fold greater potency compared with moxifloxacin (MIC(50/90)=0.12/0.25 mg/L) and at least 128-fold greater activity compared with levofloxacin (MIC(50/90)=1/ 1 mg/L) and ciprofloxacin (MIC(50/90)=1/2 mg/L) against S. pneumoniae. Haemophilus influenzae isolates were 21.9-23.3% resistant to ampicillin, but JNJ-Q2 (MIC(50/90)<=0.004/0.015 mg/L) was at least two-fold more active than moxifloxacin (MIC(50/90)=0.015/0.03 mg/L) as well as being potent against M. catarrhalis (MIC(90)=0.015/0.015 mg/L). In conclusion, JNJ-Q2 demonstrated increased potency compared with other marketed fluoroquinolones that have been used to treat CABP pathogens, thus favouring further clinical development. PMID- 22306240 TI - Iron overload-induced rat liver injury: Involvement of protein tyrosine nitration and the effect of baicalin. AB - Baicalin has been reported to protect against liver injury in iron-overload mice, however, the mechanisms underlying the hepatoprotective properties of baicalin are poorly understood. In this study, we systematically studied the protective effect of baicalin on iron overload induced liver injury, as well as the underlying mechanism based on nitrative stress in rat model. We found that when iron overload rats (500mgiron/kg) were fed baicalin-containing diet (0.3% and 1% w/w) for 45days, baicalin dose dependently protected against iron overload induced liver injury, including alleviation of hepatic pathological damage, decrease of SOD activity, iron content, carbonyl content, and the thiobarbituric acid-reactive substances level in hepatic tissues. It also increased serum iron content, SH content and GPx activity, decreased serum ALT and AST activities. Immunohistochemistry and immunoprecipitation analysis revealed that baicalin could also inhibit iron overload induced protein tyrosine nitration in liver. Moreover, in iron overload rat liver, we found that baicalin decreased the iron overload increased level of glutathione-S-transferases (GSTs) expression, oxidation and nitration. These results suggest that not only oxidative stress, but also nitrative stress, is involved in iron overload induced liver injury, and the underlying mechanism might partially relate to the involvement of GSTs expression and post-translational modification. Baicalin can effectively prevent iron overload caused abnormality and can be a candidate medicine for iron overload diseases. PMID- 22306241 TI - The glial cell modulators, ibudilast and its amino analog, AV1013, attenuate methamphetamine locomotor activity and its sensitization in mice. AB - Over 800,000 Americans abuse the psychomotor stimulant, methamphetamine, yet its abuse is without an approved medication. Methamphetamine induces hypermotor activity, and sensitization to this effect is suggested to represent aspects of the addiction process. Methamphetamine's regulation of 3'-5'-cyclic adenosine monophosphate (cAMP) levels may be partially responsible for its behavioral effects, and compounds that inhibit phosphodiesterase (PDE), the enzyme that degrades cAMP, can alter methamphetamine-induced behaviors. Methamphetamine also activates glial cells and causes a subsequent increase in pro-inflammatory cytokine levels. Modulation of glial cell activation is associated with changes in behavioral responses, and substances that oppose inflammatory activity can attenuate drug-induced behaviors. Ibudilast (aka AV411; 3-isobutyryl-2 isopropylpyrazolo-[1,5-a]pyridine), inhibits both PDE and glial pro-inflammatory activity. Ibudilast's amino analog, AV1013, modulates similar glial targets but negligibly inhibits PDE. The present study determined whether ibudilast and AV1013 would attenuate methamphetamine-induced locomotor activity and its sensitization in C57BL/6J mice. Mice were treated b.i.d. with ibudilast (1.8-13 mg/kg), AV1013 (10-56 mg/kg) or their vehicles intraperitoneally for 7 days, beginning 48 h before 5 days of daily 1-h locomotor activity tests. Each test was initiated by either a methamphetamine (3 mg/kg) or a saline injection. Ibudilast significantly (P<0.05) reduced the acute, chronic, and sensitization effects of methamphetamine's locomotor activity without significantly affecting activity by itself. AV1013 had similar anti-methamphetamine effects, suggesting that glial cell activity, by itself, can modulate methamphetamine's effects and perhaps serve as a medication target for its abuse. PMID- 22306242 TI - Acute and chronic methylphenidate alters prefrontal cortex neuronal activity recorded from freely behaving rats. AB - Today's students around the world are striking deals to buy and sell the drug methylphenidate (MPD) for cognitive enhancement. Our knowledge on the effects of MPD on the brain is very limited. The present study was designed to investigate the acute and chronic effect of MPD on the prefrontal cortex (PFC) neurons. On experimental day 1 (ED1) recordings were obtained following saline injections and after 2.5 mg/kg MPD. On ED2 through ED6, daily single 2.5 mg/kg MPD was given followed by 3 washout days (ED7 to 9). On ED10, neuronal recordings were resumed from the same animal after saline and MPD injection similar to that obtained at ED1. Ninety PFC units were recorded, all responded to the initial MPD injection, 66 units (73%) increased their activity at ED10. Recordings were resumed for the 66 units that increased their firing rate at ED1, and following MPD injection 54 units (82%) exhibited significant increases in their baseline firing rates compared to ED1 baseline. When these 54 units were rechallenged (chronic effect) with MPD, 39/54 (72%) exhibited reduction in their firing rate which can be interpreted as tolerance. From the 24 (27%) units that responded to MPD at ED1 by decreasing their activity, 14 units (58%) exhibited a decrease in their baseline firing rates at ED10 compared to ED1 baseline. However, following MPD rechallenge of these 14 units, 11 units (79%) exhibited an increase in their firing rate which is interpreted as sensitization. In conclusion, all PFC units modified their neural baseline activity. PMID- 22306243 TI - Inhibitory effect of calcitonin gene-related peptide on hypoxia-induced rat pulmonary artery smooth muscle cells proliferation: role of ERK1/2 and p27. AB - Calcitonin gene-related peptide (CGRP) inhibits angiotensin II-induced proliferation of aortic smooth muscle cells via inactivation of extracellular signal-regulated protein kinase 1/2 (ERK1/2). ERK1/2 is necessary for the degradation or down-regulation of the cell cycle inhibitor p27, and is also crucial in mediating proliferation of pulmonary artery smooth muscle cells (PASMCs). Whether ERK1/2/p27 signal pathway is involved in CGRP-mediated pathogenesis of pulmonary hypertension and vascular remodeling remains unknown. Pulmonary hypertension was induced by hypoxia in rats, and capsaicin (50 mg/kg, s.c.) was used to deplete endogenous CGRP. Proliferation of cultured PASMCs was determined by BrdU incorporation method and flow cytometry. The expression/level of CGRP, p27, ERK1/2, c-fos and c-myc was analyzed by radioimmunoassay, immunohistochemistry, real-time PCR or Western blot. Sensory CGRP depletion by capsaicin exacerbated hypoxia-induced pulmonary hypertension in rats, as shown by an increase in right ventricle systolic pressure, mean pulmonary artery pressure and vascular hypertrophy, accompanied with decreased p27 expression and increased expression of phosphorylated ERK1/2, c-fos and c-myc. Exogenous application of CGRP significantly inhibited hypoxia-induced proliferation of PASMCs concomitantly with increased p27 expression and decreased expression of phosphorylated ERK1/2, c-fos and c-myc. These effects of CGRP were abolished in the presence of CGRP(8-37). Knockdown of p27 also reversed the inhibitory effect of CGRP on proliferation of PASMCs and expression of c-fos and c-myc, but not on ERK1/2 phosphorylation. These results suggest that CGRP inhibits hypoxia-induced proliferation of PASMCs via ERK1/2/p27/c-fos/c-myc pathway. Down-regulation of CGRP may contribute to remodeling of pulmonary arteries in hypoxia-induced pulmonary hypertension. PMID- 22306244 TI - Beta-asarone attenuates ischemia-reperfusion-induced autophagy in rat brains via modulating JNK, p-JNK, Bcl-2 and Beclin 1. AB - Beta-asarone has significant pharmacological effects on the central nervous system. It can attenuate neuronal apoptosis, but its effects on the brain ischemia-reperfusion-induced autophagy have not been reported yet. Our study was a two-stage procedure: evaluation of beta-asarone effects on the autophagy at first, and then analysis of the possible mechanism. The middle cerebral artery occlusion (MCAO) model was adopted to make the brain injure and Beclin 1 was used to evaluate the autophagy. We hypothesized that the mechanism might be related to c-Jun N-terminal kinases (JNK), phospho-JNK (p-JNK), Bcl-2 and Beclin 1. To test this hypothesis, we evaluated JNK, p-JNK, Bcl-2 and Beclin 1 levels with flow cytometry. Additionally, we divided the brain into three regions: ischemic region, ischemic penumbra, and normal region, and analyzed them respectively. We found, compared to both groups II (model control) and III (low dose), Beclin 1 levels in groups IV (medium dose) and V (high dose) were significantly decreased. Beclin 1, JNK and p-JNK levels in groups VII (beta-asarone) and VIII (JNK inhibitor) were significantly decreased, but Bcl-2 levels were significantly increased. Additionally, Beclin 1, JNK, p-JNK and Bcl-2 levels among the three regions had no significant differences. We conclude that beta-asarone can attenuate the autophagy in a dose-dependent manner. The mechanism is likely that beta-asarone can decrease JNK and p-JNK levels at first, and then increase Bcl-2 level, finally interfere with the functions of Beclin 1 during the execution of autophagy. Additionally, beta-asarone can attenuate autophagy in a widespread manner. PMID- 22306245 TI - Protective effect of atorvastatin on bone tissue in orchidectomised male albino Wistar rats. AB - Recent studies have shown that atorvastatin influences bone metabolism. We investigated its bone protective effect in orchidectomised rats after 12 weeks of treatment. Eight-week-old rats were divided into 3 groups: sham-operated group, control group after orchidectomy and experimental group after orchidectomy with atorvastatin administration (12 mg/kg/day). Bone mineral density and bone marker concentrations of aminoterminal propeptide of procollagen type I (PINP), osteoprotegerin (OPG), insulin-like growth factor 1 (IGF-1) in serum, and carboxy terminal cross-linking telopeptide of type I collagen (CTX-I), bone alkaline phosphatase (BALP), bone morphogenetic protein 2 (BMP-2) in bone homogenate were measured. Total serum calcium and tibial calcium content was determined. Femurs were used for three-point bending test of the shaft and compression testing of the femoral neck. Bone markers (CTX-I, BALP, BMP-2) in control rats were higher vs. sham-operated rats. Atorvastatin reduced CTX-I, BMP-2 and OPG compared to controls. IGF-1 was decreased in control rats vs. sham-operated rats; atorvastatin increased IGF-1 vs. control rats. Atorvastatin exerts a positive effect on bone metabolism by increasing bone mineral density of the whole body, which had decreased under the effects of orchidectomy. Three-point bending test revealed an increase in maximal load values of the left femurs after atorvastatin administration compared to controls. The diameter of the left femur and length of both femurs were increased after atorvastatin administration compared to controls. Our findings suggest that atorvastatin has a beneficial effect on bone metabolism in orchidectomised rats by decreasing bone turnover, with resulting improvement in bone mineral density and bone biomechanical properties. PMID- 22306246 TI - The effects of galanin on neuropathic pain in streptozotocin-induced diabetic rats. AB - Diabetic neuropathy is a common complication associated with diabetes and is frequently painful. However, mechanisms responsible for diabetic neuropathic pain are still unclear. Experimental evidence has shown that the galanin and its receptor are involved in pain sensitization. The objective of the present study was to investigate the role of galanin and its receptor antagonist or agonist on neuropathic pain in streptozotocin-induced diabetic rats. The expression of galanin, galanin receptors 1 and 2 in dorsal root ganglion (DRG) and spinal dorsal horn (SDH) in diabetic rats were detected by Western blot assay. The effects of galanin, galanin receptor antagonist M35, galanin receptor 1 agonist M617, and galanin receptor 2 agonist AR-M1896 on neuropathic pain were evaluated by mechanical stimuli. The results showed that (1) the diabetic rats showed a significant mechanical hyperalgesia between 4 and 12weeks; (2) galanin receptor 1 expression decreased in SDH in diabetic rats; (3) galanin receptor 2 expression decreased in DRG and SDH in diabetic rats; (4) intrathecal administration of exogenous galanin attenuated diabetic neuropathic pain, this effect could be blocked by pre-treatment with galanin receptor antagonist M35; and (5) intrathecal administration of galanin receptor 1 agonist M617, but not galanin receptor 2 agonist AR-M1896, attenuated diabetic neuropathic pain. These results imply that galanin acts through receptor 1, but not galanin receptor 2, to exert analgesic effect in diabetic neuropathic pain and is one of the potential therapeutic targets on diabetic neuropathic pain sensitization. PMID- 22306247 TI - Silencing of FAD synthase gene in Caenorhabditis elegans upsets protein homeostasis and impacts on complex behavioral patterns. AB - BACKGROUND: FAD synthase is a ubiquitous enzyme that catalyses the last step of FAD biosynthesis, allowing for the biogenesis of several flavoproteins. In humans different isoforms are generated by alternative splicing, isoform 1 being localized in mitochondria. Homology searching in Caenorabditis elegans leads to the identification of two human FAD synthase homologues, coded by the single copy gene R53.1. METHODS: The C. elegans R53.1 gene was silenced by feeding. The expression level of transcripts was established by semi-quantitative RT-PCR. Overall protein composition was evaluated by two-dimensional electrophoresis. Enzymatic activities were measured by spectrophotometry and oxygen consumption by polarography on isolated mitochondria. RESULTS: From R53.1 two transcripts are generated by trans-splicing. Reducing by 50% the transcription efficiency of R53.1 by RNAi results in a 50% reduction in total flavin with decrease in ATP content and increase in ROS level. Significant phenotypical changes are noticed in knock-down nematodes. Among them, a significant impairment in locomotion behaviour possibly due to altered cholinergic transmission. At biochemical level, impairment of flavoenzyme activities and of some KCN-insensitive oxygen-consuming enzymes is detected. At proteomic level, at least 15 abundant proteins are affected by R53.1 gene silencing, among which superoxide dismutases. CONCLUSION AND GENERAL SIGNIFICANCE: For the first time we addressed the existence of different isoforms of FAD-metabolizing enzymes in nematodes. A correlation between FAD synthase silencing and flavoenzyme derangement, energy shortage and redox balance impairment is apparent. In this aspect R53.1-interfered nematodes could provide an animal model system for studying human pathologies with alteration in flavin homeostasis/flavoenzyme biogenesis. PMID- 22306248 TI - Number of microparticles generated during acute myocardial infarction and stable angina correlates with platelet activation. AB - BACKGROUND AND AIMS: Elevated levels of circulating microparticles (MPs) have been reported in patients with acute myocardial infarction (AMI) and coronary artery disease. Platelet activation and inflammation have been recognized during AMI and stable angina (SA). We hypothesize that the origin and count of MPs in AMI and SA patients are related to markers of inflammation and platelet activation. METHODS: Platelet, monocytes and endothelial MPs and surface P selectin were determined in 12 AMI patients, 10 SA patients and 9 controls by flow cytometry. Plasma P-selectin, CD40 ligand (sCD40L) and interleukin 6 (IL-6) levels were evaluated by ELISA methods. RESULTS: The total MP count was compared in control subjects, AMI, and SA patients: 12,765 (8465) vs. 38,750 (11,931) vs. 29,715 (12,072) counts/MUl (p = 0.01), respectively. Patients with AMI displayed higher levels of total and platelet origin- tissue factor-positive (CD42/CD142) MPs than patients with SA: 72.8 (6.2) vs. 56.2 (6.4) %, p = 0.001. Levels of soluble P-selectin were significantly elevated in patients with AMI as compared to SA patients: 146 (6.5) vs. 107 (2.7) ng/mL, p = 0.005; significant correlation between total MP count and relative number of CD34, CD51, CD42-positive MPs, and the P-selectin expression was observed in patients with AMI. CONCLUSIONS: Platelet activation in AMI is associated with increased generation of MPs not only from platelets, but also monocytes and endothelial cells. It suggests that interactions between platelets, monocytes and endothelial cells play an important role in the pathogenesis of myocardial ischemia. PMID- 22306249 TI - Contribution of NAD(P)H quinone oxidoreductase 1 (NQO1) Pro187Ser polymorphism and risk of colorectal adenoma and colorectal cancer in Caucasians: a meta analysis. AB - BACKGROUND AND AIMS: The effects of polymorphism of NAD(P)H quinone oxidoreductase 1 (NQO1 Pro187Ser, rs1800566) on the risks of colorectal adenoma and cancer have been widely studied and results remain controversial. Therefore, the aim of this meta-analysis was to quantitatively assess the relationships. METHODS: Databases of Medline, Embase and Wanfang were retrieved until May 15, 2011. Pooled odds ratio (OR) and 95% confidence interval (95% CI) as effect sizes were calculated by using fixed- or random-effect model. Cochrane Q-test was used to explore between-study heterogeneity; p <0.10 indicated statistical significance. RESULTS: A total of 12 case-control studies with 11,700 individuals (including 5528 cases and 6172 controls) were included in this meta-analysis. Of these studies, four studies conducted in Caucasian populations were for colorectal adenoma, and eight studies were for colorectal cancer. NQO1 187Ser allele was significantly associated with increased risk of colorectal adenoma in co-dominant and dominant comparison models (OR = 1.07, 95% CI = 1.04-1.32 for ProSer vs. ProPro and OR = 1.19, 95% CI = 1.06-1.33 for Ser carries vs. ProPro), without between-study heterogeneity. Overall, NQO1 Pro187Ser was not associated with risk of colorectal cancer, without between-study heterogeneity. Subgroup analyses indicated that Ser allele was significantly associated with increased risk of colorectal cancer for Caucasians (OR = 1.14, 95% CI = 1.00-1.30 for ProSer vs. ProPro and OR = 1.16, 95% CI = 1.02-1.31 for Ser carries vs. ProPro). CONCLUSIONS: This meta-analysis suggested that Ser allele of NQO1 Pro187Ser significantly contributed to the increased risks of colorectal adenoma and cancer in Caucasians. PMID- 22306250 TI - Highlights in clinical autonomic neuroscience: latest developments in the early detection of diabetic autonomic neuropathy. PMID- 22306251 TI - Distribution, structure and projections of the frog intracardiac neurons. AB - Histochemistry for acetylcholinesterase was used to determine the distribution of intracardiac neurons in the frog Rana temporaria. Seventy-nine intracardiac neurons from 13 frogs were labelled iontophoretically by the intracellular markers Alexa Fluor 568 and Lucifer Yellow CH to determine their structure and projections. Total neuronal number per frog heart was (Mean +/- SE) 1374 +/- 56. Largest collections of neurons were found in the interatrial septum (46%), atrioventricular junction (25%) and venal sinus (12%). Among the intracellularly labelled neurons, we found the cells of unipolar (71%), multipolar (20%) and bipolar (9%) types. Multiple processes originated from the neuron soma, hillock and proximal axon. These processes projected onto adjacent neuron somata and cardiac muscle fibers within the interatrial septum. Average total length of the processes from proximal axon was 348 +/- 50 MUm. Average total length of processes from soma and hillock was less, 118 +/- 27 MUm and 109 +/- 24 MUm, respectively. The somata of 59% of neurons had bubble- or flake-shaped extensions. Most neurons from the major nerves in the interatrial septum sent their axons towards the ventricle. In contrast, most neurons from the ventral part of the interatrial septum sent their axons towards the atria. Our findings contradict to a view that the frog intracardiac ganglia contain only non dendritic neurons of the unipolar type. We conclude that the frog intracardiac neurons are structurally complex and diverse. This diversity may account for the complicated integrative functions of the frog intrinsic cardiac ganglia. PMID- 22306252 TI - Manual defibrillation using paddles--which is the best technique? PMID- 22306253 TI - Comparison of methods for the determination of cardiopulmonary resuscitation chest compression fraction. AB - OBJECTIVE: While cardiopulmonary resuscitation (CPR) chest compression fraction (CCF) is associated with out-of-hospital cardiac arrest (OHCA) outcomes, there is no standard method for the determination of CCF. We compared nine methods for calculating CCF. METHODS: We studied consecutive adult OHCA patients treated by Alabama Emergency Medical Services (EMS) agencies of the Resuscitation Outcomes Consortium (ROC) during January 1, 2010 to October 28, 2010. Paramedics used portable cardiac monitors with real-time chest compression detection technology (LifePak 12, Physio-Control, Redmond, WA). We performed both automated CCF calculation for the entire care episode as well as manual review of CPR data in 1 min epochs, defining CCF as the proportion of each treatment interval with active chest compressions. We compared the CCF values resulting from 9 calculation methods: (1) mean CCF for the entire patient care episode (automated calculation by manufacturer software), (2) mean CCF for first 3 min of patient care, (3) mean CCF for first 5 min, (4) mean CCF for first 10 min, (5) mean CCF for the entire episode except first 5 min, (6) mean CCF for last 5 min, (7) mean CCF from start to first shock, (8) mean CCF for the first half of resuscitation, and (9) mean CCF for the second half of resuscitation. We compared CCF for Methods 2-9 with Method 1 using paired t-tests with a Bonferroni-adjusted p-value of 0.006 (99.5% confidence intervals). RESULTS: Among 102 adult OHCA, patient demographics were: mean age 60.3 years (SD 20.8 years), African American 56.9%, male 63.7%, and shockable ECG rhythm 23.5%. Mean CPR duration was 728 s (95% CI: 647-809 s). Mean CCF for the 9 CCF calculation methods were: (1) 0.587%; (2) 0.526%; (3) 0.541%; (4) 0.566%; (5) 0.562%; (6) 0.597%; (7) 0.530%; (8) 0.550%; and (9) 0.590%. Compared with Method 1, Method 7 CCF (start to first shock) was slightly lower ( 0.057; 99.5% CI: -0.100 to -0.014). There were no other statistically significant CCF differences (range: -0.054 to 0.013). Correlation between CCF 2-9 and CCF varied (rho=0.48-0.85). CONCLUSION: CCF varies minimally with different calculation methods. Automated CCF determination may prove sufficient for evaluating CPR quality. PMID- 22306254 TI - Use of beta-blockers for the treatment of cardiac arrest due to ventricular fibrillation/pulseless ventricular tachycardia: a systematic review. AB - INTRODUCTION: Advanced Life Support guidelines recommend the use of epinephrine during Cardiopulmonary Resuscitation (CPR), as to increase coronary blood flow and perfusion pressure through its alpha-adrenergic peripheral vasoconstriction, allowing minimal rises in coronary perfusion pressure to make defibrillation possible. Contrasting to these alpha-adrenergic effects, epinephrine's beta stimulation may have deleterious effects through an increase in myocardial oxygen consumption and a reduction of subendocardial perfusion, leading to postresuscitation cardiac dysfunction. OBJECTIVE: The present paper consists of a systematic review of the literature regarding the use of beta-blockade in cardiac arrest due to ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT). METHODS: Studies were identified through MEDLINE electronic databases research and were included those regarding the use of beta-blockade during CPR. RESULTS: Beta-blockade has been extensively studied in animal models of CPR. These studies not only suggest that beta-blockade could reduce myocardial oxygen requirements and the number of shocks necessary for defibrillation, but also improve postresuscitation myocardial function, diminish arrhythmia recurrences and prolong survival. A few case reports described successful beta-blockade use in patients, along with two prospective human studies, suggesting that it could be safe and effectively used during cardiac arrest in humans. CONCLUSION: Even though the existing literature points toward a beneficial effect of beta-blockade in patients presenting with cardiac arrest due to VF/pulseless VT, high quality human trials are still lacking to answer this question definitely. PMID- 22306255 TI - Long-term prognosis following resuscitation from out-of-hospital cardiac arrest: role of aetiology and presenting arrest rhythm. AB - OBJECTIVE: Little is known about long-term prognosis following resuscitation from out-of-hospital cardiac arrest, especially as it relates to the presenting rhythm or arrest aetiology. We investigated long-term survival among those discharged alive following resuscitation according to presenting rhythm and arrest aetiology. METHODS: We conducted a cohort investigation of all non-traumatic adult out-of-hospital cardiac arrest patients resuscitated and discharged alive from hospital between January 1, 2001 and December 31, 2009 in a large metropolitan emergency medical service system. Information about demographics, circumstances, presenting arrest rhythm and aetiology was collected using the dispatch, EMS, and hospital records. Long-term vital status was ascertained using state death records and the Social Security Death Index through 31st December 2010. We used Kaplan Meier to evaluate survival. RESULTS: During the study period, a total of 1001/5958 (17%) persons were resuscitated and discharged alive, of whom 313/1001 (31%) presented with a non-shockable rhythm and 210/1001 (21%) had a non-cardiac aetiology. Overall median survival was 9.8 years with 64% surviving >5 years. Five-year survival was 43% for non-shockable rhythms compared to 73% for shockable rhythms, and 45% for non-cardiac aetiology compared to 69% for cardiac aetiology (p<0.001 respectively). CONCLUSION: Cardiac arrest due to non-shockable rhythm or non-cardiac aetiology comprises a substantial proportion of those who survive to hospital discharge. Although long-term survival in these groups is less than their shockable or cardiac aetiology counterparts, nearly half are alive 5 years following discharge. The findings support efforts to improve resuscitation care for those with non-shockable rhythms or non-cardiac cause. PMID- 22306256 TI - Eleven years of experience with extracorporeal cardiopulmonary resuscitation for paediatric patients with in-hospital cardiac arrest. AB - PURPOSE: The study aims to describe 11 years of experience with extracorporeal cardiopulmonary resuscitation (ECPR) for in-hospital paediatric cardiac arrest in a university affiliated tertiary care hospital. METHODS: Paediatric patients who received extracorporeal membrane oxygenation (ECMO) during active extracorporeal cardiopulmonary resuscitation (ECPR) at our centre from 1999 to 2009 were included in this retrospective study. The results from three different cohorts (1999-2001, 2002-2005 and 2006-2009) were compared. Survival rates and neurological outcomes were analysed. Favourable neurological outcome was defined as paediatric cerebral performance categories (PCPC) 1, 2 and 3. RESULTS: We identified 54 ECPR events. The survival rate to hospital discharge was 46% (25/54), and 21 (84%) of the survivors had favourable neurological outcomes. The duration of CPR was 39+/-17 min in the survivors and 52+/-45 min in the non survivors (p=NS). The patients with pure cardiac causes of cardiac arrest had a survival rate similar to patients with non-cardiac causes (47% (18/38) vs. 44% (7/16), p=NS). The non-survivors had higher serum lactate levels prior to ECPR (13.4+/-6.4 vs. 8.8+/-5.1 mmol/L, p<0.01) and more renal failure after ECPR (66% (19/29) vs. 20% (5/25), p<0.01). The patients resuscitated between 2006 and 2009 had shorter durations of CPR (34+/-13 vs. 78+/-76 min, p=0.032) and higher rates of survival (55% (16/29) vs. 0% (0/8), p=0.017) than those resuscitated between 1999 and 2002. CONCLUSIONS: In our single-centre experience with ECPR for paediatric in-hospital cardiac arrest, the duration of CPR has become shorter and outcomes have improved in recent years. Higher pre-ECPR lactate levels and the presence of post-ECPR renal failure were associated with increased mortality. The presence of non-cardiac causes of cardiac arrest did not preclude successful ECPR outcomes. The duration of CPR was not significantly associated with poor outcomes in this study. PMID- 22306257 TI - Prediction of the neurological outcome with intrathecal high mobility group box 1 and S100B in cardiac arrest victims: a pilot study. AB - OBJECTIVES: To investigate whether high mobility group box 1 (HMGB1) and S100B in cerebrospinal fluid (CSF) and the serum predict the neurological outcome in patients resuscitated from out-of-hospital cardiac arrest (OHCA). MATERIALS AND METHODS: This study was designed as a prospective observational study. Twenty five patients, who received standard cardiopulmonary resuscitation and post resuscitation intensive care, were enrolled in this study. The patients were divided into two groups according to Glasgow-Pittsburgh Cerebral Performance categories (CPCs) at 6 months after return of spontaneous circulation (ROSC), Group G (n = 7, CPC 1 or 2) and Group P (n = 18, CPC >= 3). Their blood samples were taken at 6, 24, and 48h after ROSC. The patients, whose CSF was sampled at 48h, were also divided into either sub-Group G (n = 6) or sub-Group P (n = 8) at 6 months after ROSC. RESULTS: HMGB1 and S100B in CSF in sub-Group P were significantly higher than those in sub-Group G (HMGB1, <1.0 vs. 12.4 ng/ml, P = 0.009; S100B, 2.68 vs. 84.2 ng/ml, P = 0.007, respectively). HMGB1 in CSF was strongly correlated with S100B (sigma = 0.81, P = 0.001). HMGB1 was elevated in serum at 6h and normalized within 48 h after ROSC without any significant differences between the two groups. Serum S100B in Group P was significantly higher than that in Group G at each time point. CONCLUSIONS: The significant elevations of HMGB1 and S100B in CSF, and S100B in serum are associated with the neurologically poor outcome in OHCA patients. PMID- 22306258 TI - Estimating the impact of off-balancing forces upon cardiopulmonary resuscitation during ambulance transport. AB - INTRODUCTION: Survival from out-of-hospital cardiac arrest (OOH-CA) remains poor, especially when patients are transported with CPR in progress. Previous investigations suggest that CPR quality erodes during transport due to the austere environment. We sought to determine how frequently ambulance personnel are exposed to off-balancing forces during transport of OOH-CA patients and to estimate the potential impact on CPR and coronary perfusion pressure (CPP). METHODS: An onboard monitoring system was utilized to record acceleration data during the transport of 50 OOH-CA patients. Acceleration vectors were calculated for every second of drive time (speed >0 m/s). A model was constructed to estimate the potential impact of these vectors upon CPR and CPP. These data were then compared to a case-control cohort of 102 matched non-urgent transports. RESULTS: A total of 5.8h of drive time was analyzed in the cardiac arrest cohort. Mean transport time was 8 min 53 s with a mean drive time of 6 min 58 s. Critical acceleration threshold was exceeded 60% of transport time (202.42 min, mean 4.05 min/transport) yielding a potential hands-off ratio of 0.42 with a CPP<15 mmHg 62% of drive time. Ambulance speed was inversely related to the magnitude of off balancing forces. Comparison to 14.1h of control cohort yielded similar off balancing forces and relationships despite lower speeds and no "lights and siren" use. CONCLUSION: Critical acceleration forces occur frequently during transport of OOH-CA patients and may directly effect CPR quality and thereby CPP. These force vectors are stronger and more frequent at slower speeds, comprising the majority of ambulance drive time. Reducing speed or transporting OOH-CA patients without lights and sirens does little to mitigate these forces. PMID- 22306260 TI - Emergency physician-initiated extracorporeal cardiopulmonary resuscitation. AB - CONTEXT: Extracorporeal cardiopulmonary resuscitation (ECPR) refers to emergent percutaneous veno-arterial cardiopulmonary bypass to stabilize and provide temporary support of patients who suffer cardiopulmonary arrest. Initiation of ECPR by emergency physicians with meaningful long-term patient survival has not been demonstrated. OBJECTIVE: To determine whether emergency physicians could successfully incorporate ECPR into the resuscitation of patients who present to the emergency department (ED) with cardiopulmonary collapse refractory to traditional resuscitative efforts. DESIGN: A three-stage algorithm was developed for ED ECPR in patients meeting inclusion/exclusion criteria. We report a case series describing our experience with this algorithm over a 1-year period. RESULTS: 42 patients presented to our ED with cardiopulmonary collapse over the 1 year study period. Of these, 18 patients met inclusion/exclusion criteria for the algorithm. 8 patients were admitted to the hospital after successful ED ECPR and 5 of those patients survived to hospital discharge neurologically intact. 10 patients were not started on bypass support because either their clinical conditions improved or resuscitative efforts were terminated. CONCLUSION: Emergency physicians can successfully incorporate ED ECPR in the resuscitation of patients who suffer acute cardiopulmonary collapse. More studies are necessary to determine the true efficacy of this therapy. PMID- 22306259 TI - Perturbation of the endothelial glycocalyx in post cardiac arrest syndrome. AB - BACKGROUND: The prognosis of immediate survivors of cardiac arrest remains poor, as the majority of these patients develops an inflammatory disorder known as the post-cardiac arrest syndrome (PCAS). Recently, the endothelial glycocalyx has been shown to be a key modulator of vascular permeability and inflammation, but its role in PCAS remains unknown. METHODS: Plasma levels of the glycocalyx components syndecan-1, heparan sulfate and hyaluronic acid were measured in 25 patients after immediate survival of cardiac arrest during different phases of PCAS. Twelve hemodynamically stable patients with acute coronary syndrome served as controls. RESULTS: Cardiac arrest resulted in a significant increase in syndecan-1, heparan sulfate and hyaluronic acid levels compared to controls, indicating a shedding of the endothelial glycocalyx as a pathophysiological component of the post cardiac arrest syndrome. The time course differed between the individual glycocalyx components, with a higher increase of syndecan-1 in the early phase of PCAS (2.8-fold increase vs. controls) and a later peak of heparan sulfate (1.7-fold increase) and hyaluronic acid (2-fold increase) in the intermediate phase. Only the plasma levels of syndecan-1 correlated positively with the duration of CPR and negatively with the glycocalyx-protective protease inhibitor antithrombin III. Plasma levels of both syndecan-1 and heparan sulfate were higher in eventual non-survivors than in survivors of cardiac arrest. CONCLUSION: Our data for the first time demonstrates a perturbation of the endothelial glycocalyx in immediate survivors of cardiac arrest and indicate a potential important role of this endothelial surface layer in the development of post-cardiac arrest syndrome. PMID- 22306261 TI - A new approach to touch down method using betaine as co-solvent for increased specificity and intensity of GC rich gene amplification. AB - Tissue specific genes that contain high GC segments are difficult to amplify by standard PCR. We report an improved method for successful amplification of gene segment that has >70% GC base pairs. This new method of touch down PCR differed by having an initial annealing temperature (Ta) 1.5 degrees C below the primers melting temperature that descended 0.2 degrees C per cycle for 20 cycles and continued thereafter at fixed Ta for next 15 cycles. Different co-solvents were tested with this method to improve the result and betaine proved better than the other co-solvents. This new method is economical, fast and specific in amplifying GC rich region of other genes also. PMID- 22306262 TI - Do microRNAs regulate bone marrow stem cell niche physiology? AB - The adult bone marrow, situated within the bone cavity, comprises three distinct stem cell populations: hematopoietic stem cells (HSCs), mesenchymal stromal/stem cells (MSCs) and endothelial progenitor/stem cells (EPCs). HSCs are a well characterized population of self-renewing cells that give rise to all blood cells. The definition of MSCs is more complex due to the limited understanding of MSC properties. In general, MSCs are considered multipotent stromal cells that are able to differentiate into various cell types, including osteoblasts, chondrocytes and adipocytes. Compared to HSCs and MSCs, EPCs are a newly discovered population of stem/progenitor cells with the capacity to differentiate into endothelial cells, the cells forming the inner lining of a blood vessel. Although functionally different, HSCs, MSCs and EPCs, like stem cells in general, share the ability to self-renew and differentiate into one or more cell types. The homeostasis inside the bone marrow and within the entire body is sustained by an intricate network of growth factors and transcription factors that orchestrate the proliferation and differentiation of these multipotent stem/progenitor cells. Increasing evidence indicates that microRNAs (miRNAs), small non-coding RNAs, are among the key players of this concert. This review summarizes the current insights into miRNA-mediated regulation of bone marrow stem/progenitor cell maintenance and differentiation. Furthermore, the potential contribution of miRNAs in bone marrow stem cell niches is discussed. PMID- 22306263 TI - CUX1 transcription factors: from biochemical activities and cell-based assays to mouse models and human diseases. AB - ChIP-chip and expression analyses indicated that CUX1 transcription factors regulate a large number of genes and microRNAs involved in multiple cellular processes. Indeed, in proliferating cells CUX1 was shown to regulate several genes involved in DNA replication, progression into S phase and later, the spindle assembly checkpoint that controls progression through mitosis. siRNA mediated knockdown established that CUX1 is required for cell motility. Moreover, higher expression of short CUX1 isoforms, as observed in many cancers, was shown to stimulate cell migration and invasion. In parallel, elevated expression particularly in higher grade tumors of breast and pancreatic cancers implicated CUX1 in tumor initiation and progression. Indeed, transgenic mouse models demonstrated a causal role of CUX1 in cancers originating from various cell types. These studies revealed that higher CUX1 expression or activity not only stimulates cell proliferation and motility, but also promotes genetic instability. CUX1 has also been implicated in the etiology of polycystic kidney diseases, both from a transgenic approach and the analysis of CUX1 activity in multiple mouse models of this disease. Studies in neurobiology have uncovered a potential implication of CUX1 in cognitive disorders, neurodegeneration and obesity. CUX1 was shown to be expressed specifically in pyramidal neurons of the neocortex upper layers where it regulates dendrite branching, spine development, and synapse formation. In addition, modulation of CUX1 expression in neurons of the hypothalamus has been associated with changes in leptin receptor trafficking in the vicinity of the primary cilium resulting in altered leptin signaling and ultimately, eating behavior. Overall, studies in various fields have allowed the development of several cell-based assays to monitor CUX1 function and have extended the range of organs in which CUX1 plays an important role in development and tissue homeostasis. PMID- 22306264 TI - Integrative gene network analysis provides novel regulatory relationships, genetic contributions and susceptible targets in autism spectrum disorders. AB - Autism spectrum disorders (ASDs) are a group of diseases exhibiting impairment in social drive, communication/language skills and stereotyped behaviors. Though an increased number of candidate genes and molecular interactions have been identified by various approaches, the pathogenesis remains elusive. Based on clinical observations, data from accessible GWAS and expression datasets we identified ASDs gene candidates. Integrative gene network and a novel CNV-centric Node Network (CNN) analysis method highlighted ASDs-associated key elements and biological processes. Functional analysis identified neurological functions including synaptic cholinergic receptor (CHRNA) families, dopamine receptor (DRD2), and correlations between social behavior and oxytocin related pathways. CNN analysis of genome-wide genetic and expression data identified inheritance related clusters related to PTEN/TSC1/FMR1 and mTor/PI3K regulation. Integrative analysis identified potential regulators of networks, specifically TNF and beta estradiol, suggesting a potential central role in ASDs. Our data provide information on potential disease mechanisms, and key regulators that may generate novel postulations, and diagnostic molecular biomarkers. PMID- 22306265 TI - Detergent-induced activation of the hepatitis C virus genotype 1b RNA polymerase. AB - Recently, we found that sphingomyelin bound and activated hepatitis C virus (HCV) 1b RNA polymerase (RdRp), thereby recruiting the HCV replication complex into lipid raft structures. Detergents are commonly used for resolving lipids and purifying proteins, including HCV RdRp. Here, we tested the effect of detergents on HCV RdRp activity in vitro and found that non-ionic (Triton X-100, NP-40, Tween 20, Tween 80, and Brij 35) and twitterionic (CHAPS) detergents activated HCV 1b RdRps by 8-16.6 folds, but did not affect 1a or 2a RdRps. The maximum effect of these detergents was observed at around their critical micelle concentrations. On the other hand, ionic detergents (SDS and DOC) completely inactivated polymerase activity at 0.01%. In the presence of Triton X-100, HCV 1b RdRp did not form oligomers, but recruited more template RNA and increased the speed of polymerization. Comparison of polymerase and RNA-binding activity between JFH1 RdRp and Triton X-100-activated 1b RdRp indicated that monomer RdRp showed high activity because JFH1 RdRp was a monomer in physiological conditions of transcription. Besides, 502H plays a key role on oligomerization of 1b RdRp, while 2a RdRps which have the amino acid S at position 502 are monomers. This oligomer formed by 502H was disrupted both by high salt and Triton X-100. On the contrary, HCV 1b RdRp completely lost fidelity in the presence of 0.02% Triton X 100, which suggests that caution should be exercised while using Triton X-100 in anti-HCV RdRp drug screening tests. PMID- 22306266 TI - A case of bulbar type cerebral palsy: representative symptoms of dorsal brainstem syndrome. AB - In this study, we present the case of a 2-year-old boy who exhibited facial and bulbar paralysis since birth, severe dysphagia, signs of oculomotor disturbance, jaw jerks, pyramidal signs on both toes, intellectual disability, and severe gastroesophageal reflux. His blink reflex and auditory/somatosensory evoked potentials suggested abnormalities in the lower brainstem, and magnetic resonance imaging showed a T2 hyperintense area in the pontine tegmentum. These findings combined with the patient's symptoms suggested "dorsal brainstem syndrome" and indicated a possibility of prenatal asphyxia in this patient. Nosologic issues regarding this subgroup of cerebral palsy are discussed here. PMID- 22306267 TI - Murine mutants in the study of systemic iron metabolism and its disorders: an update on recent advances. AB - Many past and recent advances in the field of iron metabolism have relied upon the use of mouse models of disease. These models have arisen spontaneously in breeder colonies or have been engineered for global or conditional ablation or overexpression of select genes. Full phenotypic characterization of these models typically involves maintenance on iron-loaded or -deficient diets, treatment with oxidative or hemolytic agents, breeding to other mutant lines or other stresses. In this review, we focus on systemic iron biology and the contributions that mouse model-based studies have made to the field. We have divided the field into three broad areas of research: dietary iron absorption, regulation of hepcidin expression and cellular iron metabolism. For each area, we begin with an overview of the current understanding of key molecular and cellular determinants then discuss recent advances. Finally, we conclude with brief comments on prospects for future study. This article is part of a Special Issue entitled: Cell Biology of Metals. PMID- 22306268 TI - Cyclin D1 is a NF-kappaB corepressor. AB - NF-kappaB regulates the expression of Cyclin D1 (CD1), while RAC3 is an NF-kappaB coactivator that enhances its transcriptional activity. In this work, we investigated the regulatory role of CD1 on NF-kappaB activity. We found that CD1 inhibits NF-kappaB transcriptional activity through a corepressor function that can be reverted by over-expressing RAC3. In both, tumoral and non-tumoral cells, the expression pattern of RAC3 and CD1 is regulated by the cell cycle, showing a gap between the maximal expression levels of each protein. The individual increase, by transfection, of either CD1 or RAC3 enhances cell proliferation. However the simultaneous and constitutive over-expression of both proteins has an inhibitory effect. Our results suggest that the relative amounts of CD1 and RAC3, and the timing of expression of these oncogenes could tilt the balance of tumor cell proliferation in response to external signals. PMID- 22306270 TI - The regulation of cardiac activity by nitric oxide (NO) in the Vietnamese stick insect, Baculum extradentatum. AB - This study examines the role of the unconventional gaseous signaling molecule nitric oxide (NO) on the regulation of heart rate in the Vietnamese stick insect, Baculum extradentatum. Using nicotinamide dinucleotide hydrogen phosphate (NADPH) diaphorase histochemistry, as well as immunohistochemistry and Western blotting with an antibody against NO synthetase (NOS), we identified the presence of NOS in hemocytes present throughout the lumen of the dorsal vessel. We propose that NO is delivered to heart muscle tissue via hemocytes circulating within the hemolymph. In the present study, stimulation of NO levels by the application of the NO donor MAHMA-NONOate and l-arginine led to a dose-dependent decrease in heart rate. Treatment of tissues with the NOS inhibitor, L-NAME, in equimolar concentrations with l-arginine, led to a recovery of heart rate, without modifying heart rate on its own. Finally guanosine 3',5'-cyclic monophosphate (cGMP) analog, 8-bromo-cGMP, elicited similar inhibitory effects on stick insect heart rate as did the guanylate cyclase activator, YC-1, and the phosphodiesterase inhibitor, dipyridamole, indicating that cGMP is most likely the second messenger in the stick insect NO signaling pathway. Contrary to the cardioexcitatory effect of NO on other insect hearts, we have found that NO inhibits stick insect heart rate independently from any nervous system input, in a similar inhibitory fashion as that of vertebrate hearts. PMID- 22306269 TI - Transcriptome signature in young children with acute otitis media due to Streptococcus pneumoniae. AB - Streptococcus pneumoniae (Spn) is the predominant causative organism of acute otitis media in children. To better understand the genes that are regulated at the onset of AOM caused by Spn infection in the middle ear, the transcriptome profile of peripheral blood mononuclear cells isolated from children prior to and during an AOM event was evaluated by microarray. We found that 1903 (6.2%) of 29,187 genes were differentially regulated greater than 2-fold at the onset of AOM compared to the pre-infection stage of the same children. The ontology of differentially regulated genes was dominated by those involved with the immune response. At onset of infection, genes associated with bacterial defenses were significantly up-regulated, including beta-defensin123, S100 protein A12, Toll like receptor 5, IL-10, and those involved in the classical and alternative complement pathways. Genes associated with inhibition of bacterial entry through clathrin-dependent endocytosis were also up-regulated. In contrast, genes associated with cell-mediated immune responses were broadly down-regulated. The results provide the first human transcriptome data identifying genes differentially regulated at the onset of AOM in children. PMID- 22306271 TI - Design and development of a quantitative real time PCR assay for monitoring of HTLV-1 provirus in whole blood. AB - BACKGROUND: Proviral load quantification of human T-lymphotropic virus type 1 (HTLV-1) is an essential marker for disease progression. Therefore, accurate and precise quantification of the virus is important. However, many articles published about detection and quantification of HTLV-1 virus neither reported any databank for the pre-validation of their primer and probe sequences nor stressed on its importance. Consequently, this failure may cause proviral load measurement variations of different HTLV-1 strains. OBJECTIVE: The aim of this study was to develop a TaqMan assay for HTLV-1 proviral load quantification which is based on a conserved region of tax gene with minimal sequence variability. STUDY DESIGN: For the purpose of finding the most conserved region of tax gene, all the HTLV-1 Gene Bank records including tax gene sequence (524 records by December 2009) were aligned in order to design on the most conserved region of this gene. The specificity, sensitivity, inter and intra assay and the dynamic range of the assay were experimentally determined by their respective methodology. RESULT: The assay has a dynamic range of 10-10(7) HTLV-1 plasmid DNA/rxn (reaction) and the limit of detection (LOD) less than 10 copies/rxn. The assay gave coefficient of variation (CV) for the Ct values of less than 1% and 4.8% for intra and inter assay, respectively. Clinical sensitivity and specificity were determined to be 97.8% and 100%, respectively. CONCLUSION: This TaqMan assay is able to reliably quantify proviral load due to the fact that it has been designed on a conserved region of HTLV-1 tax gene with minimal sequence variability. PMID- 22306272 TI - Development and evaluation of an assay for HIV-1 protease and reverse transcriptase drug resistance genotyping of all major group-M subtypes. AB - BACKGROUND: High cost and varying sensitivity for non-B HIV-1 subtypes limits application of current commercial kits for HIV-1 drug resistance genotyping of all major HIV-1 group-M subtypes. OBJECTIVES: Our research aimed to develop and validate an assay specific for all major HIV-1 group-M subtypes for use as an alternative to commercial assays for HIV-1 protease (PR) and reverse transcriptase (RT) drug resistance genotyping. STUDY DESIGN: A nested RT-PCR encompassing the entire PR and RT up to amino acid 321 of HIV-1 was designed to detect HIV-1 group-M subtypes. Primers compatible with group-M subtypes were defined and analytical sensitivity of the assay evaluated using a panel of reference viruses for subtypes A-H and CRF01_AE. The assay was subsequently evaluated on 246 plasma samples from HIV-1 infected individuals harboring various group-M subtypes and viral loads (VLs). RESULTS: All major group-M HIV-1 subtypes were detected with an overall analytical sensitivity of 1.00E+03 RNA copies/ml. Application of the genotyping assay on 246 primarily African clinical samples comprising subtypes A (n=52; 21.7%), B (n=12; 5.0%), C (n=127; 52.9%), D (n=25; 10.4%), CRF01_AE (n=10; 4.2%), and CRF02_AG (n=10; 4.2%), and unassigned variants (n=10; 4.2%), VL range 4.32E+02-8.63E+06 (median 2.66E+04) RNA copies/ml, was ~98% successful. CONCLUSIONS: A group-M subtype-independent genotyping assay for detection of HIV-1 drug resistance was developed. The described assay can serve as an alternative to commercial assays for HIV-1 drug resistance genotyping in routine diagnostics, and for surveillance and monitoring of drug resistance in resource-limited settings (RLS). PMID- 22306273 TI - High hospital occupancy is associated with increased risk for patients boarding in the emergency department. AB - BACKGROUND: Boarding admitted patients in the emergency department due to high hospital occupancy is a worldwide problem. However, whether or not emergency department-boarded patients managed by emergency department providers subjects them to increased serious complications needs further clarification. METHODS: A multivariate logistic regression analysis was used to examine the relationship of patient's age, sex, arrival hours, diagnostic category, triage category, daily emergency department visits, and daily hospital occupancy to the occurrence of serious complications within 24 hours for 20,276 emergency admissions in a 4-year period. RESULTS: A vast majority of study days (86.5%) saw very high occupancy >=90%. Serious complications incidence was 13.62 per 1000 patient days when hospital occupancy was <=90%, and it increased significantly to 17.10 and 22.52 per 1000 patient days for occupancy at 90%-95% and >=95%, respectively. In the multivariate analysis, significant risk factors for serious complications included daily occupancy >=95% (adjusted odds ratio [OR] 1.73; 95% confidence interval [CI], 1.26-2.39), triage category (adjusted OR 0.20; 95% CI, 0.17-0.24), and specific diagnoses (injury and poisoning [adjusted OR 1.62; 95% CI, 1.22 2.84], respiratory [adjusted OR 2.48; 95% CI, 1.37-4.49], and circulatory [adjusted OR 3.24; 95% CI, 1.80-5.80]). CONCLUSION: High hospital occupancy was associated with an increased incidence of serious complications within 24 hours for patients admitted but still boarded in the emergency department and managed by emergency department providers. PMID- 22306274 TI - Interpretation of point-of-care INR results in patients treated with dabigatran. AB - BACKGROUND: Point-of-care devices for measurement of the international normalized ratio (INR) are commonly used to monitor therapy and maintain therapeutic levels of anticoagulation in patients treated with vitamin K antagonists. Dabigatran, a new oral, reversible direct thrombin inhibitor approved for stroke prevention in patients with atrial fibrillation does not require routine coagulation monitoring. However, case reports have identified falsely elevated point-of-care INR levels in patients treated with dabigatran using one of these devices (Hemochron). This in vitro study was designed to verify this issue. METHODS: We compared INR levels in whole blood and plasma using a Hemochron Jr. Signature+ point-of-care device (International Technidyne Corporation, Edison, NJ) with routine laboratory monitoring, using blood from healthy volunteers that was spiked with increasing concentrations of dabigatran. RESULTS: Prothrombin time and INR levels were increased about 2- to 4-fold with the point-of-care device compared with laboratory measures across the plasma dabigatran concentration range 50-1400 ng/mL. At plasma concentrations of dabigatran likely to be observed in patients, at a dose of 150 mg twice daily (60-275 ng/mL), whole blood point-of care INR values increased from 1.7 to 4.0, versus 1.1 to 1.5 measured with the laboratory coagulometer. Similar differences in prothrombin time were observed in plasma samples. CONCLUSIONS: INR levels in patients taking dabigatran are substantially higher using a Hemochron Jr. point-of-care device compared with laboratory values. We discourage the use of these devices specifically, as well as the use of the INR in general, for measuring the anticoagulant effect of dabigatran. PMID- 22306275 TI - Lysozyme facilitates adherence of Enterococcus faecium to host cells and induction of necrotic cell death. AB - The prevalence of infections with enterococci is increasing worldwide. However, little is known about the mechanisms which enable these opportunistic pathogens to cause infections of their host. Here we demonstrate that Enterococcus faecium in the presence of lysozyme induces necrosis in human and mouse cells after 4 h indicated by disrupted cellular membranes of epithelial (HeLa), myeloid (U937, J774A.1) and lymphoid (Jurkat J16, thymocytes), but not intestinal epithelial cells (CaCo-2, CMT-93). Using an appropriate mutant strain it was shown that the enterococcal surface-protein SgrA is involved in cell death induction in mouse cells (J774A.1, thymocytes). Microscopic analyses of epithelial cells 30 min post infection revealed that lysozyme increases adhesion of E. faecium to HeLa, but not CaCo-2 cells. At that time the phalloidin-FITC-stained cytoskeleton of infected cells was still intact, whereas 2 h post infection the F-actin network of HeLa, but not CaCo-2 cells was disrupted. Hence, the early, lysozyme-mediated increase of bacterial adherence plays an important role for cell death induction by E. faecium in HeLa cells. Moreover, bacterial extracellular hydrogen peroxide might contribute to necrosis induction, since the rate of propidium iodide positive HeLa and J774A.1 cells was lowered after infection with a ROS-deficient E. faecium mutant. PMID- 22306276 TI - A rational approach to the regioselective deacetylation of 2',3',5'-tri-O acetyluridine by Novozym 435 catalysed alcoholysis. AB - To give a rational explanation for the behaviour of 2',3',5'-tri-O-acetyluridine (TAU) catalysed alcoholysis using Novozym 435, the commercial biocatalyst with immobilized Candida antarctica lipase B (CALB), a set of experiments analyzing the role of the alcohol/substrate (A/S) molar ratio, alcohol/biocatalyst (A/B) and substrate/biocatalyst (S/B) mass ratios were carried out. At a A/S=120 and a S/B=6.16, 2',3'-di-O-acetyluridine (DAU) was obtained in 92% at 22h. The observed trend towards the exclusive formation of DAU at very high alcohol amounts can be explained on the basis of the change of substrate orientation from normal to inverse. The simple molecular modelling analysis supports that key O/H atoms from TAU and the resulting intermediates display the adequate distances to generate productive binding only when the inverse coordination of TAU is present through the 5'-moiety of TAU, at high ethanol concentrations. At these conditions a possible allosteric-like effect of ethanol, combined with water in an H-network in the catalytic triad and in its neighbourhood, could explain the high selectivity towards the production of DAU at selected conditions. PMID- 22306277 TI - The neurobiology and genetics of Attention-Deficit/Hyperactivity Disorder (ADHD): what every clinician should know. AB - This review, addressed mainly to clinicians, considers commonly asked questions related to the neuroimaging, neurophysiology, neurochemistry and genetics of Attention-Deficit/Hyperactivity Disorder (ADHD). It provides answers based on the most recent meta-analyses and systematic reviews, as well as additional relevant original studies. Empirical findings from neurobiological research into ADHD reflect a shift in the conceptualisation of this disorder from simple theoretical views of a few isolated dysfunctions to more complex models integrating the heterogeneity of the clinical manifestations of ADHD. Thus, findings from structural and functional neuroimaging suggest the involvement of developmentally abnormal brain networks related to cognition, attention, emotion and sensorimotor functions. Brain functioning alterations are confirmed by neurophysiological findings, showing that individuals with ADHD have elevated theta/beta power ratios, and less pronounced responses and longer latencies of event-related potentials, compared with controls. At a molecular level, alterations in any single neurotransmitter system are unlikely to explain the complexity of ADHD; rather, the disorder has been linked to dysfunctions in several systems, including the dopaminergic, adrenergic, serotoninergic and cholinergic pathways. Genetic studies showing a heritability of ~60-75% suggest that a plethora of genes, each one with a small but significant effect, interact with environmental factors to increase the susceptibility to ADHD. Currently, findings from neurobiological research do not have a direct application in daily clinical practice, but it is hoped that in the near future they will complement the diagnostic process and contribute to the long-term effective treatment of this impairing condition. PMID- 22306278 TI - Clinical Stevens-Johnson syndrome and rufinamide: a clinical case. PMID- 22306279 TI - Absence of clinical symptoms upon introduction of egg into the diet of milk allergic infants not previously sensitised to egg. AB - BACKGROUND: It is unclear how many children suffering from IgE mediated cow's milk allergy are sensitised to egg in early life and what the clinical implication of this sensitisation is. It is also unclear if those not sensitised to egg in early life, do later on develop sensitisation and clinical allergy to egg. METHODS: This study examines the prevalence of egg sensitisation among infants with allergy to cow's milk, prior to and following the introduction of egg and what this sensitisation clinically means. RESULTS: The percentage of egg sensitised children seen among the group of children with cow's milk allergy was 43.2%, and predictive factors for egg sensitisation are discussed. 81.8% of the sensitised patients presented with symptoms when exposed to egg in at least one of its forms, although up to 54.5% of patients tolerated boiled egg and egg-based products. Of the non-sensitised patients, the vast majority (92.5%) did not present with symptoms after the introduction of egg in their diet. CONCLUSIONS: Coexistence of allergy to egg and milk allergy is common, and it is recommended that these patients be monitored, since children who are sensitised to egg despite having never been exposed to it in their diet, may present with symptoms immediately following first ingestion. Most children who are initially non sensitised to egg do not require special care, and it is not generally recommended to delay or monitor these children, although a small number may have subsequently reacted to egg. PMID- 22306280 TI - Antifilarial activity of marine sponge Haliclona oculata against experimental Brugia malayi infection. AB - The present study incorporates the findings on in vitro and in vivo antifilarial activity in the marine sponge, Haliclona oculata using an experimental rodent infection of human lymphatic filarial parasite, Brugia malayi. The in vitro antifilarial action was determined on both adult female worms as well as microfilariae using two parameters viz. adverse effect on motility and inhibition in MTT reduction by the treated adult parasite over control worm. The antifilarial activity could be located in the methanol extract and one of its four fractions (chloroform). Bioactivity guided fractionation of chloroform fraction led to localization of in vitro activity in one of its eight chromatographic fractions. Methanol extract, chloroform fraction and one of the chromatographic fractions revealed IC(50) values of 5.00, 1.80, and 1.62MUg/ml, respectively when adult B. malayi were exposed to these test samples for 72h at 37 degrees C. Under similar exposure conditions, the IC(50) values for microfilariae were 1.88, 1.72 and 1.19MUg/ml, respectively. The active test samples were found to be safe revealing >10 selectivity indices (SI) on the basis of cytotoxicity to Vero cells (monkey kidney cells) and therefore selected for in vivo evaluation against primary (adult B. malayi intraperitoneal transplanted jird) and secondary (subcutaneous infective larvae induced mastomys) screens. In primary jird model, the three test samples at 100mg/kg for five consecutive days by subcutaneous route demonstrated significant macrofilaricidal efficacy to the tune of 51.3%, 64% and 70.7% by methanol extract, chloroform and chromatographic fraction, respectively. The three samples demonstrated 45-50% macrofilaricidal activity with moderate embryostatic effect in secondary model at 5*500, 5*250 and 5*125mg/kg by oral route. Chromatographic fraction possessing highest antifilarial action was primarily found to be a mixture of four alkaloids Mimosamycin, Xestospongin-C, Xestospongin-D and Araguspongin-C in addition to few minor compounds. PMID- 22306281 TI - Antigen, antibody and immune complex detection in serum samples from rats experimentally infected with Strongyloides venezuelensis. AB - In order to establish an antigen, antibody and immune complex detection by enzyme linked immunosorbent assay (ELISA) in serum samples, normal or immunocompromised Wistar rats experimentally infected with Strongyloides venezuelensis were used. The microtitre plates were coated with IgG anti-S. venezuelensis for antigen and immune complex detection and with alkaline parasite extract for antibody detection. Analysis revealed at least 12.5 MUg/mL of S. venezuelensis specific antigens in serum samples. Assay for antigen detection was not a good approach for evaluating infection in normal or immunocompromised rats. In normal rats IgG specific for S. venezuelensis was preferentially detected during the first 13 days post-infection (p.i.) and immune complex detection was significantly reduced in 21 p.i. day. On the other hand, in immunocompromised rats, IgG and immune complex were detected during the entire kinetic (5, 8, 13 and 21 p.i). These results suggest that immune complex screening seems to be an alternative for early strongyloidiasis diagnosis in immunocompromised individuals. PMID- 22306282 TI - Genetic diversity and natural selection at the domain I of apical membrane antigen-1 (AMA-1) of Plasmodium falciparum in isolates from Iran. AB - The apical membrane antigen-1 (AMA-1) of Plasmodium falciparum is a prime malaria asexual blood-stage vaccine candidate. Antigenic variation is one of the main obstacles in the development of a universal effective malaria vaccine. The extracellular region of P. falciparum AMA-1 (PfAMA-1) consists of three domains (I-III), of which the domain I is the most diverse region of this antigen. The objective of our study was to investigate and analyze the extent of genetic diversity and the effectiveness of natural selection at the AMA-1 domain I of P. falciparum in isolates from Iran. A fragment of ama-1 gene spanning domain I was amplified by nested PCR from 48 P. falciparum isolates collected from two major malaria endemic areas of Iran during 2009 to August 2010 and sequenced. Genetic polymorphism and statistical analyses were performed using DnaSP and MEGA software packages. Analysis of intrapopulation diversity revealed relatively high nucleotide and haplotype diversity at the PfAMA-1 domain I of Iranian isolates. Neutrality tests provided strong evidence of positive natural selection acting on the sequenced gene region. The findings also demonstrated that, in addition to natural selection, intragenic recombination may contribute to the diversity observed at the domain I. The results obtained will have significant implications in the design and the development of an AMA-1-based vaccine against falciparum malaria. PMID- 22306283 TI - The reproductive cycle of the Tasmanian devil (Sarcophilus harrisii) and factors associated with reproductive success in captivity. AB - Numbers of wild Tasmanian devils are declining as a result of the fatal, transmissible Devil Facial Tumor Disease. A captive insurance population program has been initiated but current captive breeding rates are sub-optimal and therefore the goal of this project was to increase our understanding of the estrous cycle of the devil and elucidate potential causes of failed male-female pairings. Temporal patterns of fecal progestagen and corticosterone metabolite concentrations were examined for females (n=41) in three categories of reproductive status (successful: viable young, n=20 estrous cycles; unsuccessful: paired with a male but no young confirmed, n=44 estrous cycles; non-mated: no access to a male during estrus, n=8 estrous cycles) but substantial differences were not found. Females were more likely to produce pouch young if pairing with the male extended into late proestrus (P<0.05), thereby decreasing the time between pairing and presumed ovulation. The interval between the end of proestrous elevation in progestagen metabolite concentrations and the beginning of the luteal phase was 7.6+/-2.3 days in successful females. The length of the luteal phase in successful females was 12.5+/-1.4 days which was not different from unsuccessful or non-mated females (P>0.05). Unsuccessful females had 1-3 estrous cycles within a single year. Successful females were predominantly wild caught (17/19, 90%) and most produced young following the first estrous cycle of the season (18/20, 90%). Unsuccessful females were predominantly captive born (20/27, 74%) in this study. It is possible that a proportion of females that do not produce pouch young achieve conception but the timing of reproductive failure continues to be elusive in this species. PMID- 22306284 TI - Metabolic remodeling in iron-deficient fungi. AB - Eukaryotic cells contain dozens, perhaps hundreds, of iron-dependent proteins, which perform critical functions in nearly every major cellular process. Nutritional iron is frequently available to cells in only limited amounts; thus, unicellular and higher eukaryotes have evolved mechanisms to cope with iron scarcity. These mechanisms have been studied at the molecular level in the model eukaryotes Saccharomyces cerevisiae and Schizosaccharomyces pombe, as well as in some pathogenic fungi. Each of these fungal species exhibits metabolic adaptations to iron deficiency that serve to reduce the cell's reliance on iron. However, the regulatory mechanisms that accomplish these adaptations differ greatly between fungal species. This article is part of a Special Issue entitled: Cell Biology of Metals. PMID- 22306285 TI - Transneuronal tracing of airways-related sensory circuitry using herpes simplex virus 1, strain H129. AB - Sensory input from the airways to suprapontine brain regions contributes to respiratory sensations and the regulation of respiratory function. However, relatively little is known about the central organization of this higher brain circuitry. We exploited the properties of the H129 strain of herpes simplex virus 1 (HSV-1) to perform anterograde transneuronal tracing of the central projections of airway afferent nerve pathways. The extrathoracic trachea in Sprague-Dawley rats was inoculated with HSV-1 H129, and tissues along the neuraxis were processed for HSV-1 immunoreactivity. H129 infection appeared in the vagal sensory ganglia within 24 h and the number of infected cells peaked at 72 h. Brainstem nuclei, including the nucleus of the solitary tract and trigeminal sensory nuclei were infected within 48 h, and within 96 h infected cells were evident within the pons (lateral and medial parabrachial nuclei), thalamus (ventral posteromedial, ventral posterolateral, submedius, and reticular nuclei), hypothalamus (paraventricular and lateral nuclei), subthalamus (zona incerta), and amygdala (central and anterior amygdala area). At later times H129 was detected in cortical forebrain regions including the insular, orbital, cingulate, and somatosensory cortices. Vagotomy significantly reduced the number of infected cells within vagal sensory nuclei in the brainstem, confirming the main pathway of viral transport is through the vagus nerves. Sympathetic postganglionic neurons in the stellate and superior cervical ganglia were infected by 72 h, however, there was no evidence for retrograde transynaptic movement of the virus in sympathetic pathways in the central nervous system (CNS). These data demonstrate the organization of key structures within the CNS that receive afferent projections from the extrathoracic airways that likely play a role in the perception of airway sensations. PMID- 22306286 TI - Regular exercise cures depression-like behavior via VEGF-Flk-1 signaling in chronically stressed mice. AB - In animals, chronic stress leads to the development of depression-like behavior and decreases neurogenesis and blood vessel density in hippocampus, whereas antidepressants increase adult neurogenesis in hippocampus. Regular exercise training also has antidepressant action and increases hippocampal neurogenesis; however, whether exercise-induced antidepressant action is related to hippocampal microvasculature is unclear. To address this issue, we compared depression-like behavior, blood vessel density, and neurogenesis in hippocampal dentate gyrus between stressed and exercised mice with or without administration of inhibitor of vascular endothelial growth factor (VEGF) receptor. Chronic stress led to the development of depression-like behavior, decreased blood vessel density, and neurogenesis in hippocampus. Regular exercise training improved depression-like behavior, the decrease of hippocampal blood vessel density, and neurogenesis in the stress state, whereas the combination of regular exercise and administration of SU1498, VEGF receptor Flk-1 inhibitor, canceled the exercise-induced antidepressant effect. These findings suggested that the improvement of hippocampal blood vessel and adult neurogenesis via VEGF signaling pathway is necessary for exercise-induced antidepressant effect. PMID- 22306287 TI - Pediatric clerkship directors' social networking use and perceptions of online professionalism. AB - OBJECTIVE: The use of social networking sites (SNS) is increasing among all ages, with implications for medical education faculty and trainee interactions. Our objective was to understand pediatric medical educators' use of SNS and perspectives on professional boundaries and posted content. METHODS: From September through December 2010, the Council on Medical Student Education in Pediatrics conducted its annual online survey. This survey included 11 questions regarding members' own SNS use, interactions with trainees, and perceptions about online behaviors by students. In addition, 3 open-ended questions about reasons for SNS use/nonuse and interactions with trainees were included. Bivariate and multivariable analyses were conducted with the use of logistic regression for predictors of clerkship directors' SNS use and views about behaviors. Open-ended questions were analyzed qualitatively to identify themes. RESULTS: Of the 65% (94/144) of clerkship directors responding to the survey, 34% (32/94) currently use SNS, 54% (51/94) never used SNS, and 12% (11/94) previously used SNS. Lack of time was the main reason for non-use. Female respondents were more likely to perceive it as never/rarely acceptable to accept students' friend requests (odds ratio = 2.96, P = .03). Most felt hypothetical student online behaviors were rarely/never acceptable, such as photos of students holding alcohol (68/92, 74%), using discriminatory language (89/91, 98%), and sexually explicit posts (87/90, 97%). CONCLUSIONS: Approximately one-third of pediatric clerkship directors currently use SNS, with use less likely with increasing age. Fewer have SNS relationships with students than with residents. Perceptions of appropriateness of faculty SNS behaviors and students' postings varied. These perceptions by medical education leaders can stimulate discussion to inform consensus guidelines on professional SNS use. PMID- 22306288 TI - Ethnoknowledge of Bukusu community on livestock tick prevention and control in Bungoma district, western Kenya. AB - ETHNOPHARMACOLOGICAL RELEVANCE: To date, nomadic communities in Africa have been the primary focus of ethnoveterinary research. The Bukusu of western Kenya have an interesting history, with nomadic lifestyle in the past before settling down to either arable or mixed arable/pastoral farming systems. Their collective and accumulative ethnoveterinary knowledge is likely to be just as rich and worth documenting. AIM OF THE STUDY: The aim of the present study was to document indigenous knowledge of the Bukusu on the effect of livestock ticks and ethnopractices associated with their management. It was envisaged that this would provide a basis for further research on the efficacy of these practices that could also lead to the discovery of useful tick-control agents. MATERIALS AND METHODS: Non-alienating, dialogic, participatory action research (PAR) and participatory rural appraisal (PRA) approaches involving 272 women and men aged between 18 and 118 years from the Bukusu community were used. RESULTS: Ticks are traditionally classified and identified by colour, size, host range, on-host feeding sites, and habitat preference. Tick-associated problems recognised include kamabumba (local reference to East Coast fever, Anaplasmosis or Heartwater diseases transmitted by different species of livestock ticks) and general poor performance of livestock. Traditional methods of controlling ticks include handpicking, on-host use of ethnobotanical suspensions (prepared from one or more of over 150 documented plants) to kill the ticks and prevent re infestation, fumigation of infested cattle with smoke derived from burning ethnobotanical products, burning pastures, rotational grazing ethnopractices, and livestock quarantine. CONCLUSIONS: The study confirms that the Bukusu have preserved rich ethnoveterinary knowledge and practices. It provides some groundwork for elucidating the efficacy of some of these ethnopractices in protecting livestock from tick disease vectors, particularly those involving the use of ethnobotanicals, which may lead to the discovery of useful ant-tick agents. PMID- 22306289 TI - Neuroprotective effect of Buyang Huanwu decoction against focal cerebral ischemia/reperfusion injury in rats--time window and mechanism. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Buyang Huanwu Decoction, a traditional Chinese medicine, consists of different herbal medicines, and has been traditionally used for centuries to treat paralysis and stroke. However, its optimal therapeutic time window and the mechanism are still unclear. AIM OF THE STUDY: This study was designed to explore the therapeutic time window and mechanism of Buyang Huanwu Decoction on transient focal cerebral ischemia/reperfusion injury. MATERIALS AND METHODS: Middle cerebral artery occlusion was conducted in male Sprague-Dawley rats, and 40g/kg of Buyang Huanwu Decoction was intragastrically infused at different time points, and the same dose was infused every 24h for 3 days. The level of glutamate in cerebrospinal fluid and the expression of metabotropic glutamate receptor-1 RNA in striatum were detected before, during, and after ischemia/reperfusion. Neurological deficit scores and brain infarction volumes were measured at 72h after reperfusion. RESULT: Cerebral ischemia/reperfusion resulted in significant neurological deficit and extensive cerebral infarct volume, associated with a large amount of glutamate in cerebrospinal fluid and elevation of metabotropic glutamate receptor-1 RNA expression. Buyang Huanwu Decoction significantly suppressed the release of glutamate, and reduced the expression of metabotropic glutamate receptor-1 RNA. The neurological defect score and infarction volume were significantly improved by administration of Buyang Huanwu Decoction, when compared with the Ischemia group. CONCLUSIONS: Administration of Buyang Huanwu Decoction, within 4h of post-transient focal stroke, reduced significant cerebral ischemia/reperfusion damage. The neuroprotective mechanism of Buyang Huanwu Decoction is, in part, associated with the down-regulation of metabotropic glutamate receptor-1 RNA and inhibition of glutamate release resulting from cerebral ischemia. PMID- 22306290 TI - Cardiovascular responses to mental activation of social support schemas. AB - While perceived social support appears to be associated with buffered cardiovascular reactivity to short-term stressors, its impact on cardiovascular recovery is less clear. This relationship might be affected by trait hostility, with hostile individuals benefiting less from social support. However, despite the possibility that support provision might enhance well-being, limited empirical work has manipulated this in a laboratory context. The present study sought to investigate whether mentally activated support provision and support receipt influenced cardiovascular recovery from cognitive stress. Systolic blood pressure, diastolic blood pressure, heart rate, cardiac output, and total peripheral resistance were monitored continuously in a laboratory following exposure to a short-term cognitive stressor. Mixed factorial analyses of variance revealed that inducing thoughts of support provision resulted in elevated post stressor systolic and diastolic blood pressure responses (p=.03; p=.004) in comparison to thoughts of support receipt or non-supportive social contact. Furthermore, these elevations were most pronounced for individuals high in trait hostility. From this study, support provision when already cognitively and physiologically stressed appears to be deleterious rather than beneficial for cardiovascular function. Moreover, individuals high in trait hostility may be particularly disadvantaged by providing support in everyday life. PMID- 22306291 TI - A review of critical care nursing staffing, education and practice standards. AB - The aim of this paper is to review the differences and similarities in critical care nursing staffing, education and practice standards in the US, Canada, UK, New Zealand and Australia. SEARCH METHODS: A university library discovery catalogue, Science Direct, Scopus databases and professional websites were searched. Key terms used included, critical care, specialist, standards, competency, practice, scope, workforce, staffing, ratios, qualifications, adverse events, and patient outcomes. The search was limited to articles that referred to critical care environments including paediatric and neonatal settings. RESULTS: The database and hand search identified 40 relevant articles. Website searching resulted in a further 36 documents. A diversity of critical care nursing contexts and a lack of comparable workforce data made it difficult to quantify differences and similarities between countries. There is a general consensus about the importance of optimum staffing by registered nurses with a proportion of those holding relevant post-registration qualifications although there is no consistency in defining the educational preparation for a 'qualified' critical care nurse. Critical care nursing standards for the US, Canada, UK and New Zealand were predominantly developed by expert panels while the Australian standards were developed with a multi-methods study including observations of practice. All five standards documents were built upon national entry-to-practice nurse standards and contained similar constructs, although there was no construct common to all of the standards. CONCLUSION: There is a lack of evidence to support nursing staffing with post registration specialty qualifications. Existing standards are predominantly opinion based rather than supported by research. The expected standards for nursing practice are fundamentally similar. PMID- 22306292 TI - Immune and stress response 'cross-talk' in the Drosophila Malpighian tubule. AB - The success of insects is in large part due to their ability to survive environmental stress, including heat, cold, and dehydration. Insects are also exposed to infection, osmotic or oxidative stress, and to xenobiotics or toxins. The molecular mechanisms of stress sensing and response have been widely investigated in mammalian cell lines, and the area of stress research is now so vast to be beyond the scope of a single review article. However, the mechanisms by which stress inputs to the organism are sensed and integrated at the tissue and cellular level are less well understood. Increasingly, common molecular events between immune and other stress responses are observed in vivo; and much of this work stems of efforts in insect molecular science and physiology. We describe here the current knowledge in the area of immune and stress signalling and response at the level of the organism, tissue and cell, focussing on a key epithelial tissue in insects, the Malpighian tubule, and drawing together the known pathways that modulate responses to different stress insults. The tubules are critical for insect survival and are increasingly implicated in responses to multiple and distinct stress inputs. Importantly, as tubule function is central to survival, they are potentially key targets for insect control, which will be facilitated by increased understanding of the complexities of stress signalling in the organism. PMID- 22306293 TI - Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase. AB - Pyruvate kinase isoform M2 (PKM2) is a glycolysis enzyme catalyzing conversion of phosphoenolpyruvate (PEP) to pyruvate by transferring a phosphate from PEP to ADP. We report here that PKM2 localizes to the cell nucleus. The levels of nuclear PKM2 correlate with cell proliferation. PKM2 activates transcription of MEK5 by phosphorylating stat3 at Y705. In vitro phosphorylation assays show that PKM2 is a protein kinase using PEP as a phosphate donor. ADP competes with the protein substrate binding, indicating that the substrate may bind to the ADP site of PKM2. Our experiments suggest that PKM2 dimer is an active protein kinase, while the tetramer is an active pyruvate kinase. Expression of a PKM2 mutant that exists as a dimer promotes cell proliferation, indicating that protein kinase activity of PKM2 plays a role in promoting cell proliferation. Our study reveals an important link between metabolism alteration and gene expression during tumor transformation and progression. PMID- 22306294 TI - Cyclin-dependent kinases are regulators and effectors of oscillations driven by a transcription factor network. AB - During embryonic cell cycles, B-cyclin-CDKs function as the core component of an autonomous oscillator. Current models for the cell-cycle oscillator in nonembryonic cells are slightly more complex, incorporating multiple G1, S phase, and mitotic cyclin-CDK complexes. However, periodic events persist in yeast cells lacking all S phase and mitotic B-cyclin genes, challenging the assertion that cyclin-CDK complexes are essential for oscillations. These and other results led to the proposal that a network of sequentially activated transcription factors functions as an underlying cell-cycle oscillator. Here we examine the individual contributions of a transcription factor network and cyclin-CDKs to the maintenance of cell-cycle oscillations. Our findings suggest that while cyclin CDKs are not required for oscillations, they do contribute to oscillation robustness. A model emerges in which cyclin expression (thereby, CDK activity) is entrained to an autonomous transcriptional oscillator. CDKs then modulate oscillator function and serve as effectors of the oscillator. PMID- 22306295 TI - Ex vivo fucosylation improves human cord blood engraftment in NOD-SCID IL 2Rgamma(null) mice. AB - Delayed engraftment remains a major hurdle after cord blood (CB) transplantation. It may be due, at least in part, to low fucosylation of cell surface molecules important for homing to the bone marrow microenvironment. Because fucosylation of specific cell surface ligands is required before effective interaction with selectins expressed by the bone marrow microvasculature can occur, a simple 30 minute ex vivo incubation of CB hematopoietic progenitor cells with fucosyltransferase-VI and its substrate (GDP-fucose) was performed to increase levels of fucosylation. The physiologic impact of CB hematopoietic progenitor cell hypofucosylation was investigated in vivo in NOD-SCID interleukin (IL) 2Rgamma(null) (NSG) mice. By isolating fucosylated and nonfucosylated CD34(+) cells from CB, we showed that only fucosylated CD34(+) cells are responsible for engraftment in NSG mice. In addition, because the proportion of CD34(+) cells that are fucosylated in CB is significantly less than in bone marrow and peripheral blood, we hypothesize that these combined observations might explain, at least in part, the delayed engraftment observed after CB transplantation. Because engraftment appears to be correlated with the fucosylation of CD34(+) cells, we hypothesized that increasing the proportion of CD34(+) cells that are fucosylated would improve CB engraftment. Ex vivo treatment with fucosyltransferase-VI significantly increases the levels of CD34(+) fucosylation and, as hypothesized, this was associated with improved engraftment. Ex vivo fucosylation did not alter the biodistribution of engrafting cells or pattern of long-term, multilineage, multi-tissue engraftment. We propose that ex vivo fucosylation will similarly improve the rate and magnitude of engraftment for CB transplant recipients in a clinical setting. PMID- 22306296 TI - Maternal administration of busulfan before in utero transplantation of human hematopoietic stem cells enhances engraftments in sheep. AB - In utero transplantation (IUT) of human hematopoietic stem cells has been conducted in sheep, which are used as large animal models of human hematopoietic reconstitution and models for clinical IUT; however, the levels of engraftment have generally been low. Busulfan (BU), a myeloablative agent, is often administered to patients before hematopoietic stem cells transplantation to improve the engraftment. In this study, hematopoietic activity was evaluated in adult sheep after administering BU at different doses. Next, pregnant ewes were administered BU, and dams as well as their fetuses were evaluated, as BU readily crosses the sheep placenta. Then, the BU dose with the desired outcomes was selected and administered to pregnant ewes at 2 or 6 days before performing IUT using human cord blood CD34(+) cells. The engraftment was evaluated in recipients that underwent IUT in the presence or absence of BU. As a result, hematopoietic activity was safely and transiently suppressed in adult sheep treated with 5 to 7.5 mg/kg BU. BU crossed the sheep placenta, and fetal sheep were indeed conditioned by administering 3 mg/kg BU to pregnant ewes. Engraftment of human CD34(+) cells in fetal recipients was enhanced when IUT was carried out 6 days post-BU. Up to 3.3% engraftment levels (in terms of bone marrow colony-forming units) were achieved with the IUT of 0.72 to 2.4 million CD34(+) cells when BU was used. BU can be administered to pregnant ewes to effectively condition the fetal recipient for IUT with enhanced engraftment of donor cells. PMID- 22306297 TI - A functional role for the histone demethylase UTX in normal and malignant hematopoietic cells. AB - Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), an H3K27Me2/3 demethylase, has been implicated in development, self-renewal, and differentiation of various organs and embryonic stem cells through chromatin modifications and transcriptional regulation of important developmentally related genes, such as Hox genes. However, the function of UTX in hematopoiesis is not well understood. To study the role of UTX in the mammalian hematopoietic system, we used lentiviral short hairpin RNA constructs to knockdown UTX in the murine hematopoietic progenitor cell line EML, in primary murine bone marrow cells and in leukemic cell lines. We report that Utx is highly expressed in the hematopoietic compartment and that it plays an important role in cell proliferation and homeostasis of hematopoietic cells in vitro. Knockdown of UTX in EML and primary murine bone marrow cells impairs their colony-forming ability. Moreover, knockdown of UTX affects expression of key genes that regulate hematopoietic differentiation such as Mll1, Runx1, and Scl in primary murine bone marrow cells. And we further demonstrate that UTX directly associates with the promoters of the Mll1, Runx1, and Scl genes and modulate their transcription by controlling H3K27me3 marks on respective promoter regions. In addition, UTX depletion severely impaired proliferation of several human leukemia cell lines. Together, these data demonstrate a functional role for UTX in normal and malignant hematopoiesis. PMID- 22306298 TI - A delicious fly in the soup. The relationship between disgust, obesity, and restraint. AB - Disgust is a core emotion that serves to protect one from engaging in activities that promote contamination and contracting disease. Since disgust is intimately connected to ingesting food, disgust sensitivity is probably also associated with dietary habits. The aim of the present study was to examine the relationship between obesity and disgust and between restraint and disgust. Participants (n=135, all female) were recruited and tested via the Internet. They indicated their desire to eat high-calorie foods and filled out several questionnaires assessing restrained eating and disgust sensitivity. We hypothesized that more restrained eaters would show increased disgust and that women with a higher BMI would show decreased disgust, which is what we found; that is, more restrained eaters showed increased core disgust and contamination disgust, whereas women with a higher BMI showed decreased core disgust and contamination disgust. Hence, feeling disgusted by food may be a strategy to uphold restraint, whereas relatively decreased disgust could encourage overeating. PMID- 22306299 TI - Why study Escherichia coli? PMID- 22306300 TI - Immunoglobulin G(1) immune complex upregulates interferon-gamma-induced nitric oxide production via ERK1/2 activation in murine microglia. AB - Intrathecal Immunoglobulin G (IgG) is elevated in some central nervous system (CNS) diseases and microglia upregulate Fcgamma receptors in various neurological disorders. However, the interaction between IgG or IgG immune complexes and microglial Fcgamma receptors is not fully understood. In this study, the effect of IgG(1) immune complexes on microglia was investigated. IgG(1) immune complexes increased nitric oxide production in murine microglia in the presence of interferon (IFN)-gamma. These effects were dependent upon IgG(1) immune complex induced activation of spleen tyrosine kinase with subsequent activation of extracellular signal regulated kinase1/2. Collectively, these results indicate that IgG(1) immune complexes can exert immunomodulatory effects in various central nervous system disorders. PMID- 22306301 TI - Dipeptidyl peptidase-IV inhibits glioma cell growth independent of its enzymatic activity. AB - Malignant gliomas exhibit abnormal expression of proteolytic enzymes that may participate in the uncontrolled cell proliferation and aberrant interactions with the brain extracellular matrix. The multifunctional membrane bound serine aminopeptidase dipeptidyl peptidase (DPP)-IV has been linked to the development and progression of several malignancies, possibly both through the enzymatic and nonenzymatic mechanisms. In this report we demonstrate the expression of DPP-IV and homologous proteases fibroblast activation protein, DPP8 and DPP9 in primary cell cultures derived from high-grade gliomas, and show that the DPP-IV-like enzymatic activity is negatively associated with their in vitro growth. More importantly, the DPP-IV positive subpopulation isolated from the primary cell cultures using immunomagnetic separation exhibited slower proliferation. Forced expression of the wild as well as the enzymatically inactive mutant DPP-IV in glioma cell lines resulted in their reduced growth, migration and adhesion in vitro, as well as suppressed glioma growth in an orthotopic xenotransplantation mouse model. Microarray analysis of glioma cells with forced DPP-IV expression revealed differential expression of several candidate genes not linked to the tumor suppressive effects of DPP-IV in previous studies. Gene set enrichment analysis of the differentially expressed genes showed overrepresentation of gene ontology terms associated with cell proliferation, cell adhesion and migration. In conclusion, our data show that DPP-IV may interfere with several aspects of the malignant phenotype of glioma cells in great part independent of its enzymatic activity. PMID- 22306302 TI - Neurofascin: a switch between neuronal plasticity and stability. AB - Neurofascin (NF) is a cell surface protein belonging to the immunoglobulin superfamily (IgSF). Different polypeptides of 186, 180, 166 and 155 kDa are generated by alternative splicing. Expression of these isoforms is temporally and spatially regulated and can be roughly grouped into embryonic, adult and glial expression. NF interacts with many different interaction partners both extra- and intracellularly. Interactions of NF166 and NF180 selectively regulate mechanisms of plasticity like neurite outgrowth and the formation postsynaptic components. By contrast, NF155 and NF186 confer stabilization of neural structures by interaction with voltage-gated sodium channels and ankyrinG at axon initial segments (AIS) or nodes of Ranvier as well as neuron-glia interactions at the paranodes. Alternatively spliced isoforms of neurofascin may therefore balance dynamic and stabilizing mechanisms of the CNS. PMID- 22306303 TI - 2009 H1N1 vaccination by pregnant women during the 2009-10 H1N1 influenza pandemic. AB - OBJECTIVE: Pregnant women were identified at greater risk and given priority for 2009 H1N1 vaccination during the 2009 through 2010 H1N1 pandemic. We identified factors associated with acceptance or refusal of 2009 H1N1 vaccination during pregnancy. STUDY DESIGN: We conducted an in-person survey of postpartum women on the labor and delivery service from June 17 through Aug. 13, 2010, at 4 New York hospitals. RESULTS: Of 1325 survey respondents, 34.2% received 2009 H1N1 vaccination during pregnancy. A provider recommendation was most strongly associated with vaccine acceptance (odds ratio [OR], 19.4; 95% confidence interval [CI], 12.7-31.1). Also more likely to take vaccine were women indicating the vaccine was safe for the fetus (OR, 12.4; 95% CI, 8.3-19.0) and those who previously took seasonal flu vaccination (OR, 7.9; 95% CI, 5.8-10.7). Race, education, income, and age were less important in accepting vaccine. CONCLUSION: Greater emphasis on vaccine safety and provider recommendation is needed to increase the number of women vaccinated during pregnancy. PMID- 22306304 TI - Impact of fetal gender on the labor curve. AB - OBJECTIVE: We sought to estimate the association between fetal gender and first stage labor curve at term. STUDY DESIGN: Within a large, retrospective cohort study of consecutive, singleton term labor patients who delivered in the second stage, we compared the active phase of first-stage labor by fetal gender. The primary outcome was length of active stage 1. Interval-censored regression was used to estimate the effect of fetal gender on the duration of active first stage (4-10 cm) and was adjusted for relevant covariates. RESULTS: Of 2400 women, 2373 women had complete labor information and were available for this analysis. Male gender was associated with both a statistically significantly longer active first stage of labor (4.6 vs 4.0 hours; P = .002) and stratified analyses by parity and labor type. CONCLUSION: Male fetuses are associated with longer active phase of the first stage of labor and, specifically, may need to be considered in the setting of arrest diagnoses. PMID- 22306305 TI - Cytotoxic and necrotic responses in human amniotic epithelial (WISH) cells exposed to organophosphate insecticide phorate. AB - The in vitro interaction of the organophosphorous insecticide (OPs) phorate with calf thymus DNA (ctDNA), and its potential to cause changes in cell cycle, membrane damage, and cytotoxicity leading to cell death (necrosis) was investigated in human amnion epithelial (WISH) cells. Fluorescence quenching revealed high binding affinity (K(a)=5.62*10(4)M(-1)) of phorate to ctDNA. Molecular modeling of the phorate-ctDNA interaction suggested the binding of phorate at AT rich regions on minor groove of DNA. The interaction ensued alkylation of the N-6, N-7 of adenine and C-4 carbonyl oxygen of thymine. Binding of phorate was stronger in the presence of the transition metal ion copper II (Cu(2+)), and has accentuated the destabilization of the DNA secondary structure. A discernable change in the voltammetric E(1/2) (E(0')) with lesser cathodic (i(pc)) and anodic (i(pa)) peak currents confirmed the formation of phorate-DNA and phorate-DNA-Cu (II) association complexes. Furthermore, the MTT and NRU assays demonstrated substantial phorate cytotoxicity due to loss of mitochondrial and lysosomal membrane integrity, and reduction in mitochondrial membrane potential (DeltaPsim) of treated WISH cells. Cell cycle analysis of WISH cells treated with 1000MUM phorate exhibited 13.7-fold (p<0.01) augmentation in the sub G(1) peak. Annexin V-PE and 7-ADD staining of phorate treated cells reaffirmed the development of late apoptotic or necrotic cell population in a concentration dependent manner. Thus, this study demonstrated the phorate induced DNA structural alterations and cellular damage in cultured human cells. PMID- 22306306 TI - Genotoxicity of 7H-dibenzo[c,g]carbazole and its methyl derivatives in human keratinocytes. AB - Differences between tissues in the expression of drug-metabolizing enzymes may substantially contribute to tissue-specificity of chemical carcinogens. To verify this hypothesis, the spontaneously immortalized human keratinocytes HaCaT were used, in order to evaluate the genotoxic potential of 7H-dibenzo[c,g]carbazole (DBC), a known hepatocarcinogen and sarcomagen, and its synthetic tissue-specific derivatives, 5,9-dimethyl-DBC (DiMeDBC) and N-methyl-DBC (N-MeDBC), which manifest specific tropism to the liver and skin, respectively. HaCaT cells mainly express cytochrome P4501A1 (CYP1A1), which is involved in metabolism of DBC and N MeDBC, but not DiMeDBC [10]. Both DBC and the sarcomagen N-MeDBC induced significant levels of DNA strand-breaks, micronuclei, and DNA adducts followed by the phosphorylation of the p53 protein and histone H2AX in HaCaT cells. In contrast, the specific hepatocarcinogen DiMeDBC was devoid of any significant genotoxic activity in this cell line. Our study demonstrates that the absence of drug-metabolizing enzyme(s) involved in DiMeDBC metabolism may contribute substantially to the tissue-specific genotoxicity of this hepatocarcinogen. PMID- 22306307 TI - Immobilization of glucosyltransferase from Erwinia sp. using two different techniques. AB - Two different techniques of glucosyltransferase immobilization were studied for the conversion of sucrose into isomaltulose. The optimum conditions for immobilization of Erwinia sp. glucosyltransferase onto Celite 545, determined using response surface methodology, was pH 4.0 and 170 U of glucosyltransferase/g of Celite 545. Using this conditions more than 60% conversion of sucrose into isomaltulose can be obtained. The immobilization of glucosyltransferase was also studied by its entrapment in microcapsules of low-methoxyl pectin and fat (butter and oleic acid). The non-lyophilized microcapsules of pectin, containing the enzyme and fat, showed higher glucosyltransferase activity, compared with lyophilized microcapsules containing enzyme plus fat, and also lyophilized microcapsules containing enzyme without fat addition. The non-lyophilized microcapsules of pectin containing the glucosyltransferase and fat, converted 30% of sucrose into isomaltulose in the first batch. However the conversion decreased to 5% at the 10th batch, indicating inactivation of the enzyme. PMID- 22306308 TI - Plant and bacterial systems biology as platform for plant synthetic bio(techno)logy. AB - The recent implementation of various high-throughput biochemical and bioanalytical platforms for the study of biological systems has resulted in a wealth of experimental information that systems biology integrates into models and functional descriptions of organisms. The fast tempo of systems biology development is currently bringing in a revolution in the understanding of cell networks by providing with a holistic comprehension of cellular components and their interaction dynamics. This thorough description of biological systems has laid the grounds for the development of synthetic biology, a discipline applying basic principles of engineering for the rational assembly of biological modules into higher order complex biological systems with desired properties. Despite the success of this new field for the generation of biotechnological tools, it has not been yet widely applied to plant systems. This review aims at describing the current status of systems biology, its contribution to our understanding of plant metabolism, expression and regulatory networks and how synthetic biology approaches could benefit utilising plant and bacterial 'omics' as a source for the design and development of biological modules for the improvement of plant stress tolerance and crop production, among other applications. The article further describes synthetic biology strategies currently being applied to plant metabolic engineering, development of signalling pathways and synthetic organelles, and the potential of this new field for the understanding of plant cellular functioning and the generation of plant biotechnological tools. PMID- 22306309 TI - Combat-related gunshot wounds in the United States military: 2000-2009 (cohort study). AB - INTRODUCTION: The armed forces of the United States are engaged in the longest conflict in their history. No prior works have described the incidence or epidemiology of gunshot wounds in the U.S. military. METHODS: All combat-related gunshot wounds sustained by uniformed servicemembers in the years 2000-2009 were identified using the Defense Medical Epidemiology Database. Demographic information for all individuals identified as having sustained gunshot injuries was obtained and like data was captured for the entire military population serving in the same time-period. Raw unadjusted incidence rates were calculated for gunshot wounds within the entire demographic, as well as for the subcategories of sex, military rank, branch of service, and age. Adjusted incidence rate ratios were also calculated via multivariate Poisson regression analysis, using subcategories with the lowest unadjusted incidence rates as referents. RESULTS: We identified 4693 gunshot wounds within a population of 13,813,333 person-years for an overall incidence of 0.34 per 1000 person-years. Marine Corps service demonstrated the highest unadjusted incidence rate at 0.68 per 1000 person-years. Male sex, Junior Enlisted rank, Army and Marine Corps service, and ages 20-29 demonstrated significant adjusted incidence rate ratios and maintained unadjusted incidence rates above the population mean. CONCLUSIONS: Male sex, Junior Enlisted rank, Army and Marine Corps service, and ages 20-29 were identified as significant independent risk factors for war-related gunshot injuries. This investigation is the first to report on the incidence and epidemiology of gunshot wounds and includes the largest cohort of individuals to sustain such injuries in the literature. PMID- 22306310 TI - Do human activities affect the picoplankton structure of the Ahe atoll lagoon (Tuamotu Archipelago, French Polynesia)? AB - The spatial variations of the picoplankton (photoautotrophic and heterotrophic microorganisms) in the Ahe atoll lagoon were studied in May and October 2008 to assess whether they were affected by human activities along the atoll. Spatial patterns were studied using 10 sampling stations chosen according to the location of the anthropogenic activities (pearl farming, harbor). Experiments were also carried out to determine whether bacterial growth, with or without predators, was limited by inorganic (N and P) substrates. The results showed that heterotrophic bacterioplankton abundance was superior to the photoautotrophic organisms, especially in May. Significant increases in bacterial abundance were observed in May after 24 h incubation with +P and +N (but not in October). All samples complied with the quality levels for fecal indicator bacteria (FIB) defined by the European Union and there was no evidence that human sewage had any impact on picoplankton over the whole atoll. PMID- 22306311 TI - Contamination of port zone sediments by metals from Large Marine Ecosystems of Brazil. AB - Sediment contamination by metals poses risks to coastal ecosystems and is considered to be problematic to dredging operations. In Brazil, there are differences in sedimentology along the Large Marine Ecosystems in relation to the metal distributions. We aimed to assess the extent of Al, Fe, Hg, Cd, Cr, Cu, Ni, Pb and Zn contamination in sediments from port zones in northeast (Mucuripe and Pecem) and southeast (Santos) Brazil through geochemical analyses and sediment quality ratings. The metal concentrations found in these port zones were higher than those observed in the continental shelf or the background values in both regions. In the northeast, metals were associated with carbonate, while in Santos, they were associated with mud. Geochemical analyses showed enrichments in Hg, Cd, Cu, Ni and Zn, and a simple application of international sediment quality guidelines failed to predict their impacts, whereas the use of site-specific values that were derived by geochemical and ecotoxicological approaches seemed to be more appropriate in the management of the dredged sediments. PMID- 22306312 TI - Evaluation of lindane diffusion along the southeastern Adriatic coastal strip (Mediterranean Sea): a case study in an Albanian industrial area. AB - This study aimed to analyze the impact at sea of a pesticide factory located 7 km north of Durres (Albania) by investigating a lowland area under the sea situated 0.7 km from the shoreline. The main product of this factory was lindane. Production ceased in 1991 during the Albanian civil war, and a large amount of industrial waste was dispersed over the ground surrounding the factory, resulting in a high level of lindane pollution. A water-scoop channels the ground water accumulated around the disused factory directly into the sea. The concentrations of lindane in sediments collected along the coasts of the region ranged from 0.60 to 22.55 ng g(-1). The average concentration in the muscles of fish did not exceed the limits specified by European Commission legislation, whereas the concentration in the liver did exceed these limits; consequently, liver is not recommended for consumption. PMID- 22306313 TI - Influence of strong monsoon winds on the water quality around a marine cage culture zone in a shallow and semi-enclosed bay in Taiwan. AB - Influences of marine cage culture and monsoonal disturbances, northeasterly (NE) and southwesterly (SW) monsoons on the proximal marine environment were investigated across a gradient of sites in a semi-enclosed bay, Magong Bay (Penghu Islands, Taiwan). Elevated levels of ammonia produced by the cages were the main pollutant and distinguished the cage-culture and intermediary zones (1000 m away from the cages) from the reference zone in the NE monsoon, indicating currents produced by the strong monsoon may have extended the spread of nutrient-enriched waters without necessarily flushing such effluents outside Magong Bay. Moreover, the levels of chlorophyll-a, dissolved oxygen, and turbidity were distinguishable between two seasons, suggesting that resuspension caused by the NE monsoon winds may also influence the water quality across this bay. It indicated that the impacts of marine cage culture vary as a function of distance, and also in response to seasonal movements of water driven by local climatic occurrences. PMID- 22306314 TI - Biochemical characterization of l-arabitol 2-dehydrogenase from Pantoea ananatis. AB - Two oxidoreductases, XDH and LAD, were found in the same operon that was involved in sugar metabolism in Pantoea ananatis. LAD, whose endogenous substrate was unknown, was recombinantly prepared and biochemically analyzed. Consequently, LAD was identified as l-arabitol 2-dehydrogenase and its substrate specificity was complementary to that of XDH. PMID- 22306315 TI - Microbial beta-glycosylation of entacapone by Cunninghamella echinulata ATCC 9245. AB - The purpose of this paper is to describe the glycosylation of entacapone by cultures of Cunninghamella echinulata ATCC 9245. This method is then applied in toxicological and pharmacological studies. The cultures were grown in a fluid PDSM medium for 7 days at 28 degrees C. After purification by silica gel flash column chromatography, the (E)-2-cyano-N,N-diethyl-3-(4-hydroxy-3-nitro-5-(3,4,5 trihydroxy-6-(hydroxymethyl)-tetrahydro-2H-pyran-2-yloxy)phenyl) acrylamide was identified by IR, mass spectroscopy and (1)H and (13)C NMR. The correct position and beta-configuration of the glucose was determined through HSQC, HMBC and NOE experiments. PMID- 22306316 TI - Smad-mediated regulation of microRNA biosynthesis. AB - microRNAs (miRNAs) are small non-coding RNAs conserved in metazoans. Depletion of miRNAs results in embryonic lethality, suggesting they are essential for embryogenesis. Similarly, pathways induced by growth factors of the transforming growth factor beta (TGF-beta) superfamily control cell growth, differentiation, and development. Recently Smad proteins, the signal transducers of the TGF-beta pathway, were found to regulate miRNA expression, which, in turn, affects expression of numerous proteins. Smads modulate miRNA expression through both transcriptional and post-transcriptional mechanisms illustrating the complexity of gene regulation by TGF-beta. In this chapter we summarize the current knowledge of mechanisms underlying Smad-mediated regulation of miRNA biogenesis. PMID- 22306317 TI - MicroRNA-203 leads to G1 phase cell cycle arrest in laryngeal carcinoma cells by directly targeting survivin. AB - Previous studies have shown that miR-203 acts as a tumor-suppressive microRNA in various cancers, but its roles in laryngeal carcinoma are still contradicted. Here, we found that miR-203 inhibited the growth of laryngeal cancer cells and survivin was a direct target of miR-203. Moreover, silencing of survivin recapitulated the effect of miR-203 on cell cycle progression, whereas overexpression of survivin reversed this effect. Additionally, qRT-PCR showed the reciprocal relationship between miR-203 and survivin in laryngeal cancer tissues. These findings indicate that miR-203 inhibits the proliferation of laryngeal carcinoma cells by directly targeting survivin, suggesting its application in anti-cancer therapeutics. PMID- 22306318 TI - OIT3 deficiency impairs uric acid reabsorption in renal tubule. AB - The oncoprotein induced transcript 3 (OIT3), also named liver-specific zona pellucida domain-containing protein (LZP), has been shown to be expressed in kidney, and was confirmed to interact with the Tamm-Horsfall glycoprotein (THP). However, the function of OIT3 in kidney remains unclear. In this study we found that serum uric acid level of Oit3 null mice was significantly lower than that in wild type controls, whereas the excretion of uric acid in urine increased in the mutant mouse. Significantly, the excretion of THP in urine also increased while renal THP decreased in Oit3 null mice. Our data suggest that OIT3 could maintain urate homeostasis by regulating the excretion and reabsorption of uric acid in renal tubule via cooperating with THP. PMID- 22306319 TI - Cripto/GRP78 modulation of the TGF-beta pathway in development and oncogenesis. AB - Cripto is a small, GPI-anchored signaling protein that regulates cellular survival, proliferation, differentiation and migration during normal developmental processes and tumorigenesis. Cripto functions as an obligatory co receptor for the TGF-beta ligands Nodal, GDF1 and GDF3 but attenuates signaling of others such as activin-A, activin-B and TGF-beta1. Soluble, secreted forms of Cripto also activate Src, ras/raf/MAPK and PI3K/Akt pathways via a mechanism that remains largely obscure. This review describes the biological roles and signaling mechanisms of Cripto, highlighting our identification of the 78 kDa glucose regulated protein (GRP78) as a cell surface receptor/co-factor required for Cripto signaling via both TGF-beta and Src/MAPK/PI3K pathways. We discuss emerging evidence indicating that Cripto/GRP78 signaling regulates normal somatic stem cells and their tumorigenic counterparts. PMID- 22306320 TI - Spread of onabotulinumtoxinA after bladder injection. Experimental study using the distribution of cleaved SNAP-25 as the marker of the toxin action. AB - BACKGROUND: OnabotulinumtoxinA (Onabot/A) has been used to treat detrusor overactivity disorders. The treatment is based on several injections of toxin throughout the bladder wall. However, injection protocols are not well established among clinicians, varying in dose and dilution. OBJECTIVE: Study the distribution and neurochemistry of cleaved synaptosome-associated protein of 25 kDa (cSNAP-25) after Onabot/A administration in the guinea pig bladder. In addition, we analyzed which factor, dose or volume, contributes more to the diffusion of the toxin. DESIGN, SETTING, AND PARTICIPANTS: Guinea pig bladders were treated with Onabot/A via intramural injection or an instillation. MEASUREMENTS: Bladder cryostat sections were processed for single or dual immunohistochemistry staining with antibodies against cSNAP-25, vesicular acetylcholine transporter, tyrosine hydroxylase, and calcitonin gene-related peptide. Different administration methods and doses were analyzed. Statistical analysis was performed using the chi-square test for colocalization studies after multiple injections and the t test for the evaluation of affected fibers after a single injection. RESULTS AND LIMITATIONS: cSNAP-25 immunoreactive fibers were abundant throughout the bladder tissue in the mucosa and muscular layer. Double labeling showed that parasympathetic fibers are more affected than sympathetic or sensory. A single Onabot/A injection is more effective if diluted in a higher volume. Onabot/A instillation in the bladder does not cleave SNAP-25 protein. CONCLUSIONS: A single Onabot/A injection spreads the neurotoxin activity to the opposite side of the guinea pig bladder. This action is more evident when high saline volumes are used to dissolve Onabot/A. The toxin cleaves the SNAP-25 protein mainly in cholinergic but also in adrenergic and sensory fibers. In contrast with intramural injection, instillation of Onabot/A does not cleave SNAP 25 in nerve fibers. PMID- 22306323 TI - A novel automated platform for quantifying the extent of skeletal tumour involvement in prostate cancer patients using the Bone Scan Index. AB - BACKGROUND: There is little consensus on a standard approach to analysing bone scan images. The Bone Scan Index (BSI) is predictive of survival in patients with progressive prostate cancer (PCa), but the popularity of this metric is hampered by the tedium of the manual calculation. OBJECTIVE: Develop a fully automated method of quantifying the BSI and determining the clinical value of automated BSI measurements beyond conventional clinical and pathologic features. DESIGN, SETTING, AND PARTICIPANTS: We conditioned a computer-assisted diagnosis system identifying metastatic lesions on a bone scan to automatically compute BSI measurements. A training group of 795 bone scans was used in the conditioning process. Independent validation of the method used bone scans obtained <=3 mo from diagnosis of 384 PCa cases in two large population-based cohorts. An experienced analyser (blinded to case identity, prior BSI, and outcome) scored the BSI measurements twice. We measured prediction of outcome using pretreatment Gleason score, clinical stage, and prostate-specific antigen with models that also incorporated either manual or automated BSI measurements. MEASUREMENTS: The agreement between methods was evaluated using Pearson's correlation coefficient. Discrimination between prognostic models was assessed using the concordance index (C-index). RESULTS AND LIMITATIONS: Manual and automated BSI measurements were strongly correlated (rho=0.80), correlated more closely (rho=0.93) when excluding cases with BSI scores>=10 (1.8%), and were independently associated with PCa death (p<0.0001 for each) when added to the prediction model. Predictive accuracy of the base model (C-index: 0.768; 95% confidence interval [CI], 0.702-0.837) increased to 0.794 (95% CI, 0.727-0.860) by adding manual BSI scoring, and increased to 0.825 (95% CI, 0.754-0.881) by adding automated BSI scoring to the base model. CONCLUSIONS: Automated BSI scoring, with its 100% reproducibility, reduces turnaround time, eliminates operator-dependent subjectivity, and provides important clinical information comparable to that of manual BSI scoring. PMID- 22306324 TI - The reproducibility of Berg Balance Scale and the Single-leg Stance in chronic stroke and the relationship between the two tests. AB - OBJECTIVE: To assess the reproducibility of the Berg Balance Scale (BBS) and the Single-leg Stance (SLS), and the validity of the SLS as an independent test of upright postural control in patients with chronic stroke. DESIGN: An intra-rater test-retest reproducibility study. The BBS and the SLS were assessed twice, 7 days apart. SETTING: A university hospital. PARTICIPANTS: Fifty individuals; 6-46 months after a stroke. MAIN OUTCOME MEASUREMENTS: The reproducibility of the BBS and the SLS was evaluated with intraclass correlation coefficient (ICC(2,1)), the mean difference between the 2 test sessions (d) with 95% confidence interval (95% CI), the standard error of measurement (standard error of measurement [SEM]%), the smallest real difference (SRD%), and the Bland-Altman graphs. To assess validity of SLS, the relationship between the SLS and the BBS was analyzed by the Pearson correlation coefficient. RESULTS: The ICC(2,1) was 0.88 for the BBS, and the ICC(2,1) values were 0.88 for the nonparetic limb and 0.92 for the paretic lower limb for the SLS. The smallest change that indicates a real improvement for a group of individuals, SEM%, was 3% for BBS, 15% for the nonparetic limb and 27% for the paretic limb for SLS. The smallest real difference for a single individual was 8% for BBS but was higher for SLS, at 42% for the nonparetic limb, and 74% for the paretic limb. There was a significant relationship between the SLS and the BBS (r = 0.65-0.79; P < .001). CONCLUSIONS: The BBS and the SLS are reproducible measurements in patients with chronic stroke, but only the BBS is sensitive enough to follow changes over time or after an intervention. The SLS is strongly related to the BBS and can be used as an independent test to measure upright postural control after a stroke. PMID- 22306325 TI - Instruction of mesenchymal cell fate by the transcription factor C/EBPbeta. AB - The transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta) plays a role in the differentiation of a large variety of cell types. C/EBPbeta was initially described as an early inducer of adipocyte differentiation, however, recent data have shown that this is not the only mesenchymal cell lineage where C/EBPbeta has an instructive function. Mouse models and tissue culture studies have now established a regulatory role of C/EBPbeta in osteoblast and in chondrocyte differentiation. These three different cell lineages are derived from the same precursor, the mesenchymal stem cell (MSC). This review will focus on the emerging role of C/EBPbeta and its different protein isoforms in various mesenchymal cell lineages and its function in adipocyte, chondrocyte and osteoblast differentiation. Moreover, the mesenchymal stem cell has attracted the attention of regenerative medicine in recent years, and the possible role of C/EBPbeta in this respect will be discussed. PMID- 22306326 TI - Genome-wide analysis of the mitogen-activated protein kinase gene family in Solanum lycopersicum. AB - Mitogen-activated protein kinases (MAPKs), a family of Ser/Thr protein kinases, play an essential role in mediating biotic and abiotic stress responses in plants. In this study, we investigated 16 putative SlMAPK genes from tomato genome and compared them with those from Arabidopsis. The full cDNA sequences of 13 novel SlMAPKs in tomato were obtained through PCR ampilification. A comprehensive genome-wide analysis of SlMAPKs in tomato is presented, including their gene structure, phylogeny, genome localization, and expression profiles. Phylogenic analysis of the 16 SlMAPKs and 20 AtMAPKs from Arabidopsis indicated that the SlMAPK genes were clustered into four major groups, and genes within the same groups had similar exon-intron structures. All SlMAPK proteins in groups A, B and C had a Thr-Glu-Tyr (TEY) activation domain, whereas those in group D contained a Thr-Asp-Tyr (TDY) activation domain. The analysis of 5'-upstream region of SlMAPKs revealed a group of putative cis-acting elements related to stress responses. Expression analysis of SlMAPK genes using RT-PCR and real-time quantitative PCR demonstrated that all SlMAPK transcripts were able to be detected in at least one investigated tissue, and some of them exhibited tissue specific expression patterns. The transcript abundance of nearly all SlMAPK genes was increased in response to heat stress treatment. Our data provided an insight into the evolution of the gene family and a useful reference for further functional analysis of MAPK family genes in tomato. PMID- 22306327 TI - The R453Q and D151A polymorphisms of hexose-6-phosphate dehydrogenase gene (H6PD) influence the polycystic ovary syndrome (PCOS) and obesity. AB - Hexose-6-phosphate dehydrogenase (H6PDH) influences 11beta-hydroxysteroid dehydrogenase activity, a key enzyme in the peripheral metabolism of cortisol that modulates insulin sensitivity in adipose tissue. To study the associations of R453Q and D151A polymorphisms in the H6PDH gene (H6PD) with polycystic ovary syndrome (PCOS) and their influence on clinical and metabolic variables, we genotyped 237 patients with PCOS and 135 control women for the R453Q (rs6688832) and D151A (rs34603401) variants in H6PD. The R453Q genotypes were distributed differently in patients and controls (chi(2)=9.55, P=0.002). Genotypes of D151A were distributed evenly in women with PCOS and controls, but showed a different distribution in non-obese and obese women (chi(2)=3.95, P=0.047), especially within the PCOS subgroup (chi(2)=4.65, P=0.031). A backward stepwise likelihood ratio logistic regression model (Nagelkerke's R(2)=0.490; chi(2)=164; P<0.0001) retained free testosterone (OR=1.13; 95% CI: 1.10-1.17) and H6PD Q453 alleles (OR=0.46; 95% CI: 0.27-0.79) as statistically significant predictors for PCOS, whereas homeostasis model assessment of insulin resistance and the H6PD D151A variant were excluded by the model. Both H6PD variants were associated with several phenotypic variables, including fasting insulin, homeostasis model assessment of insulin resistance and androstenedione levels. In summary, the R453Q and D151A variants of the H6PD gene are associated with PCOS and obesity, respectively, and may contribute to the PCOS phenotype by influencing obesity, insulin resistance and hyperandrogenism. PMID- 22306328 TI - Novel and neglected issues of acetone-butanol-ethanol (ABE) fermentation by clostridia: Clostridium metabolic diversity, tools for process mapping and continuous fermentation systems. AB - This review emphasises the fact that studies of acetone-butanol-ethanol (ABE) fermentation by solventogenic clostridia cannot be limited to research on the strain Clostridium acetobutylicum ATCC 824. Various 1-butanol producing species of the genus Clostridium, which differ in their patterns of product formation and abilities to ferment particular carbohydrates or glycerol, are described. Special attention is devoted to species and strains that do not produce acetone naturally and to the utilisation of lactose, inulin, glycerol and mixtures of pentose and hexose carbohydrates. Furthermore, process-mapping tools based on different principles, including flow cytometry, DNA microarray analysis, mass spectrometry, Raman microscopy, FT-IR spectroscopy and anisotropy of electrical polarisability, which might facilitate fermentation control and a deeper understanding of ABE fermentation, are introduced. At present, the methods with the greatest potential are flow cytometry and transcriptome analysis. Flow cytometry can be used to visualise and capture cells within clostridial populations as they progress through the normal cell cycle, in which symmetric and asymmetric cell division phases alternate. Cell viability of a population of Clostridium pasteurianum NRRL B-598 was determined by flow cytometry. Transcriptome analysis has been used in various studies including the detection of genes expressed in solventogenic phase, at sporulation, in the stress response, to compare expression patterns of different strains or parent and mutant strains, for studies of catabolite repression, and for the detection of genes involved in the transport and metabolism of 11 different carbohydrates. Interestingly, the results of transcriptome analysis also challenge our earlier understanding of the role of the Spo0A regulator in initiation of solventogenesis in C. acetobutylicum ATCC 824. Lastly, the review describes other significant recent discoveries, including the deleterious effects of intracellular formic acid accumulation in C. acetobutylicum DSM 1731 cells on the metabolic switch from acidogenesis to solventogenesis and the development of a high-cell density continuous system using Clostridium saccharoperbutylacetonicum N1-4, in which 1-butanol productivity of 7.99 g/L/h was reached. PMID- 22306329 TI - Fractional purification and bioconversion of hemicelluloses. AB - Hemicelluloses are types of plant cell wall polysaccharides, and the world's second most abundant renewable polymers after cellulose in lignocellulosic materials. They represent a type of hetero-polysaccharide with complex structure containing glucose, xylose, mannose, galactose, arabinose, rhamnose, glucuronic acid, and galacturonic acid in various amounts, depending on the source. Hemicelluloses are usually bonded to other cell-wall components such as cellulose, cell-wall proteins, lignin, and phenolic compounds by covalent and hydrogen bonds, and by ionic and hydrophobic interactions. This paper provides a review on hemicelluloses from lignocellulosic materials, especially in regard to their isolation and purification methods, and bioconversion. Current isolation and purification strategies are summarized, including: alkali peroxide extraction, organic solvent extraction, steam explosion, ultrasound-assisted extraction, microwave-assisted extraction, column chromatography, and membrane separation. In addition, the bioconversion of hemicelluloses including pretreatment, enzymatic hydrolysis, and fermentation are discussed. PMID- 22306330 TI - A review of thermal-chemical conversion of lignocellulosic biomass in China. AB - Biomass, a renewable, sustainable and carbon dioxide neutral resource, has received widespread attention in the energy market as an alternative to fossil fuels. Thermal-chemical conversion of biomass to produce biofuels is a promising technology with many commercial applications. This paper reviewed the state-of the-art research and development of thermal-chemical conversion of biomass in China with a special focus on gasification, pyrolysis, and catalytic transformation technologies. The advantages and disadvantages, potential of future applications, and challenges related to these technologies are discussed. Conclusively, these transformation technologies for the second-generation biofuels with using non-edible lignocellulosic biomass as feedstocks show prosperous perspective for commercial applications in near future. PMID- 22306331 TI - Application of metagenomic techniques in mining enzymes from microbial communities for biofuel synthesis. AB - Feedstock for biofuel synthesis is transitioning to lignocelluosic biomass to address criticism over competition between first generation biofuels and food production. As microbial catalysis is increasingly applied for the conversion of biomass to biofuels, increased import has been placed on the development of novel enzymes. With revolutionary advances in sequencer technology and metagenomic sequencing, mining enzymes from microbial communities for biofuel synthesis is becoming more and more practical. The present article highlights the latest research progress on the special characteristics of metagenomic sequencing, which has been a powerful tool for new enzyme discovery and gene functional analysis in the biomass energy field. Critical enzymes recently developed for the pretreatment and conversion of lignocellulosic materials are evaluated with respect to their activity and stability, with additional explorations into xylanase, laccase, amylase, chitinase, and lipolytic biocatalysts for other biomass feedstocks. PMID- 22306332 TI - A low-invasive and effective transcutaneous immunization system using a novel dissolving microneedle array for soluble and particulate antigens. AB - Transcutaneous immunization (TCI) is a promising needle-free, easy-to-use, and low-invasive vaccination method. The hydrogel patch-based TCI system induced immune responses against soluble antigens (Ags) like toxoids, but could not induce immune responses against particulate Ags. Here, as an effective TCI system against every form of Ag, we developed a dissolving microneedle array of three lengths (200, 300, or 800 MUm) made of hyaluronate as a novel TCI device. Unlike conventional microneedles, the microneedles of our dissolving microneedle arrays dissolved in the skin after insertion. Each dissolving microneedle array effectively delivered both soluble and particulate Ags under the stratum corneum. TCI using these dissolving microneedle arrays induced effective immune responses in rats regardless of the Ag form that were comparable to conventional vaccination using subcutaneous immunization. In addition, application of these dissolving microneedle arrays caused only slight skin irritation. These findings suggest that our TCI system can simply, safely, and effectively improve protective immune responses for every vaccine Ag. PMID- 22306333 TI - Transferrin-conjugated polyphosphoester hybrid micelle loading paclitaxel for brain-targeting delivery: synthesis, preparation and in vivo evaluation. AB - The successful treatment of central nervous system (CNS) disorders is hampered by inefficient drug delivery across the blood-brain barrier (BBB). Transferrin (Tf) could facilitate the transcytosis of coupled nanocarriers through Tf receptor (TfR) mediated pathway. In this study, Tf-modified paclitaxel-loaded polyphosphoester hybrid micells (TPM) was prepared and evaluated for its in vitro and in vivo brain-targeting efficiency. The polyphosphoester hybrid micelle formed a core-shell structure in aqueous solution, and demonstrated high drug entrapping efficiency (89.9+/-3.4%). In addition, the micelle showed negligible hemolysis even at 2.0 mg/mL. The TPM was 87.85+/-2.32 nm with zeta potentials 12.33+/-1.46 mV, and PTX showed sustained release from TPM. TPM demonstrated enhanced cellular uptake and brain accumulation, which were 2 and 1.8-fold of PM, respectively. TPM exhibited strongest anti-glioma activity, and the mean survival time of mice bearing intracranial U-87 MG glioma treated with TPM (39.5 days) was significantly longer than those treated with Taxol(r) (33.6 days). These results indicated that Tf conjugated micelle could be a promising carrier for brain targeting drug delivery. PMID- 22306334 TI - Nanopatch targeted delivery of both antigen and adjuvant to skin synergistically drives enhanced antibody responses. AB - Many vaccines make use of an adjuvant to achieve stronger immune responses. Alternatively, potent immune responses have also been generated by replacing the standard needle and syringe (which places vaccine into muscle) with devices that deliver vaccine antigen to the skin's abundant immune cell population. However it is not known if the co-delivery of antigen plus adjuvant directly to thousands of skin immune cells generates a synergistic improvement of immune responses. In this paper, we investigate this idea, by testing if Nanopatch delivery of vaccine - both the antigen and the adjuvant - enhances immunogenicity, compared to intramuscular injection. As a test-case, we selected a commercial influenza vaccine as the antigen (Fluvax 2008(r)) and the saponin Quil-A as the adjuvant. We found, after vaccinating mice, that anti-influenza IgG antibody and haemagglutinin inhibition assay titre response induced by the Nanopatch (with delivered dose of 6.5ng of vaccine and 1.4MUg of Quil-A) were equivalent to that of the conventional intramuscular injection using needle and syringe (6000ng of vaccine injected without adjuvant). Furthermore, a similar level of antigen dose sparing (up to 900 fold) - with equivalent haemagglutinin inhibition assay titre responses - was also achieved by delivering both antigen and adjuvant (1.4MUg of Quil-A) to skin (using Nanopatches) instead of muscle (intramuscular injection). Collectively, the unprecedented 900 fold antigen dose sparing demonstrates the synergistic improvement to vaccines by co-delivery of both antigen and adjuvant directly to skin immune cells. Successfully extending these findings to humans with a practical delivery device - like the Nanopatch - could have a huge impact on improving vaccines. PMID- 22306335 TI - Efficient intracellular drug-targeting of macrophages using stealth liposomes directed to the hemoglobin scavenger receptor CD163. AB - The hemoglobin scavenger receptor CD163 is exclusively expressed in the monocytic lineage and preferentially in tissue resident macrophages of the M2 phenotype and in macrophages in sites of inflammation and tumor growth. In the present study we have designed liposomes specifically targeting CD163 by hydrophobic linkage of CD163-binding monoclonal antibodies to polyethylene glycol-coated liposomes ('stealth liposomes'). Targeting to the endocytic CD163 protein greatly increased the uptake of liposomes in CD163 transfected cells and macrophages as visualized by confocal microscopy and flow cytometry of cells exposed to CD163 targeting liposomes loaded with calcein. Strong cytotoxic effects were seen in CD163 expressing human monocytes by using the chemotherapeutic agent doxorubicin as cargo of the liposomes. In conclusion, the use of stealth liposomes modified to recognize CD163 is a potential way to target drugs to macrophages that support inflammatory and malignant processes. PMID- 22306336 TI - Sustained release micellar carrier systems for iontophoretic transport of dexamethasone across human sclera. AB - A challenge in ocular drug delivery is to maintain the therapeutic concentration of a drug at the site of action in the eye. The objective of the present study was to investigate the feasibility of micellar carrier systems for sustained drug delivery in transscleral iontophoresis in vitro. Simple and mixed micelles prepared using sodium taurocholate (TA) alone or with egg lecithin (LE) were the carrier systems studied. Dexamethasone (DEX), a poorly water soluble corticosteroid, was the model drug. The micellar carrier systems were first characterized for their solubilization and encapsulation of the drug. Passive and 2-mA iontophoretic (both cathodal and anodal) transport experiments were conducted using these micellar carrier systems in side-by-side diffusion cells with excised human sclera in vitro. Drug release studies were performed after the transport experiments. Saturated DEX solution without the micellar carriers was used as a control. It was found that the solubilization capacity of the micellar carrier systems increased as the total lipid concentration of the systems increased. Drug release from the sclera was significantly prolonged with the micellar carrier systems as compared to the control after passive and iontophoretic delivery. Less than ~20% of DEX was released from the sclera in approximately 2h after cathodal iontophoretic delivery of the micellar carrier systems, whereas more than ~50% of DEX was released from the control in the same time period under the same condition. Micellar carrier systems can be a suitable transscleral drug delivery system for poorly water soluble drugs by enhancing their aqueous solubilities and providing sustained drug delivery. These micellar carrier systems can be efficiently delivered into and across the sclera by iontophoresis for drug delivery. PMID- 22306337 TI - Functional enhancement of beta cells in transplanted pancreatic islets by secretion signal peptide-linked exendin-4 gene transduction. AB - This study assessed whether the newly designed exendin-4 (Ex-4) gene with highly releasable characteristics could enhance the beta cell function, thereby attenuating the essential islet mass required to cure diabetes. We constructed a lentivirus system encoding for a highly releasable secretion signal peptide, the peptide linked Ex-4 (SP-Ex-4) gene. After the transduction of lentivirus encoding for SP-Ex-4 (LV-SP-Ex-4) gene into the islets, the therapeutic effects of Ex-4 secreted were evaluated by conducting glucose-stimulated insulin secretion and cytokine- or hypoxia-induced apoptosis. Additionally, the effect of reduced islet numbers for transplantation was evaluated via in vivo models. The transduction of LV-SP-Ex-4 gene did not affect the viability of islets. In diabetic animal models, 50 islets expressing Ex-4 were transplanted to cure the diabetic nude mice, whereas at least 150 untransduced islets had to be transplanted to cure the diabetic nude mice. When the transduced islets were transplanted into diabetic immunocompetent mice, the survival rate of the mice was 18.0+/-4.9 days; however, when the untransduced islets were transplanted, they were rejected within 10.0+/ 0.6 days. Therefore, the highly releasable Ex-4 could enhance the beta cell function with slightly enhanced viability of transplanted islets, presenting as a potential technology for overcoming islet shortage. PMID- 22306338 TI - Nanobiocomposite platform based on polyaniline-iron oxide-carbon nanotubes for bacterial detection. AB - The nanocomposite based on polyaniline (PANI)-iron oxide nanoparticles (nFe(3)O(4)) and multi walled carbon-nanotubes (CNT) has been fabricated onto indium tin oxide (ITO) coated glass plate via facile electrochemical synthesis of polyaniline in presence of nFe(3)O(4) (~20 nm) and CNT (20-80 nm in diameter). The results of transmission electron microscopic studies show evidence of coating of PANI and nFe(3)O(4) onto the CNT. The PANI-nFe(3)O(4)-CNT/ITO nanoelectrode has been characterized by Fourier transform infrared spectroscopy, X-ray diffraction and scanning electron microscopy studies. The biotinylated nucleic acid probe sequence consisting of 20 bases has been immobilized onto PANI nFe(3)O(4)-CNT/ITO nanoelectrode using biotin-avidin coupling. It is shown that the PANI-nFe(3)O(4)-CNT platform based biosensor can be used to specifically detect bacteria (N. gonorrhoeae) at minute concentration as low as (1*10(-19) M) indicating high sensitivity within 45 s of hybridization time at 298 K by differential pulse voltammetry using methylene blue as electroactive indicator. This bacterial sensor has also been tested with 4 positive and 4 negative PCR amplicons of gonorrhoea affected patient samples. The results of these studies have implications towards the fabrication of a handheld device for Neisseria gonorrhoeae detection that may perhaps result in a decrease in the human immunodeficiency virus infections. PMID- 22306339 TI - Eosinophil-derived interferon-lambda contributes to initiation of allergen related inflammation in the intestine. AB - BACKGROUND AND AIMS: Epithelial barrier dysfunction plays a critical role in the initiation of a number of immune diseases; the causative factors are not fully understood. The present study aimed to elucidate the mechanism by which the eosinophil-derived interferon (IFN)-lambda induced the gut epithelial barrier dysfunction. METHODS: The duodenal biopsies were obtained from patients with or without food allergies. The eosinophils and IFNlambda expression were observed by immune staining. Intestinal epithelial cell line, T84 cells, and a mouse model were employed to observe the effect of IFNlambda on the epithelial barrier function and the initiation of skewed T helper (Th)2 polarization in the mouse intestine. RESULTS: IFNlambda expression was observed in over 80% human eosinophils of the subjects with or without food allergies. Exposure to microbial products, lipopolysaccharide or peptidoglycan, could induce eosinophils to release IFNlambda. Exposure to IFNlambda could induce intestinal epithelial barrier dysfunction via inducing the epithelial cell apoptosis. Concurrent exposure to microbial products and food antigens could induce aberrant antigen specific Th2 polarization and Th2 pattern inflammation in the intestine. CONCLUSIONS: Eosinophils express IFNlambda that can induce intestinal epithelial barrier dysfunction and promotes the initiation of the aberrant Th2 polarization in the intestine. PMID- 22306340 TI - Synergistic anticancer activity of triptolide combined with cisplatin enhances apoptosis in gastric cancer in vitro and in vivo. AB - Cisplatin is an anticancer agent that is effective against several types of cancer, including gastric cancer. However, its therapeutic application is limited by its toxicity in normal tissues and complications caused in patients. In this study, we attempted to clarify how triptolide, an active component extracted from the traditional Chinese herbal medicine Tripterygium wilfordii Hook F (TWHF), enhances cisplatin-induced cytotoxicity in gastric cancer SC-M1 cells. After low dose combined treatments with triptolide and cisplatin, a decrease in viability with a concomitant increase in apoptosis was observed in SC-M1 cells but not in normal cells. Apoptosis induced by the combined treatments was accompanied by loss of mitochondrial membrane potential and release of cytochrome c. Triptolide increased the cisplatin-induced activation of caspase-3 and caspase-9 and the downstream cleavage of PARP in SC-M1 cells. Results of these in vitro experiments indicated that triptolide enhanced cytotoxicity in cisplatin-treated SC-M1 cells and that this effect is mediated by apoptosis through a mitochondrial pathway. Furthermore, using a SCID mouse xenograft model, we demonstrated that the combined treatment completely suppressed tumor growth via down-regulation of proliferating cell nuclear antigen expression without significant side effects. These results suggest that lower concentrations of cisplatin and triptolide used in combination may produce a synergistic anticancer effect that warrants further investigation for its potential clinical applications. PMID- 22306341 TI - Dasatinib synergizes with both cytotoxic and signal transduction inhibitors in heterogeneous breast cancer cell lines--lessons for design of combination targeted therapy. AB - Molecularly targeted therapies have emerged as the leading theme in cancer therapeutics. Multi-cytotoxic drug regimens have been highly successful, yet many studies in targeted therapeutics have centered on a single agent. We investigated whether the Src/Abl kinase inhibitor dasatinib displays synergy with other agents in molecularly heterogeneous breast cancer cell lines. MCF-7, SKBR-3, and MDA-MB 231 display different signaling and gene signatures profiles due to expression of the estrogen receptor, ErbB2, or neither. Cell proliferation was measured following treatment with dasatinib+/-cytotoxic (paclitaxel, ixabepilone) or molecularly targeted agents (tamoxifen, rapamycin, sorafenib, pan PI3K inhibitor LY294002, and MEK/ERK inhibitor U0126). Dose-responses for single or combination drugs were calculated and analyzed by the Chou-Talalay method. The drugs with the greatest level of synergy with dasatinib were rapamycin, ixabepilone, and sorafenib, for the MDA-MB-231, MCF-7, and SK-BR-3 cell lines respectively. However, dasatinib synergized with both cytotoxic and molecularly targeted agents in all three molecularly heterogeneous breast cancer cell lines. These results suggest that effectiveness of rationally designed therapies may not entirely rest on precise identification of gene signatures or molecular profiling. Since a systems analysis that reveals emergent properties cannot be easily performed for each cancer case, multi-drug regimens in the near future will still involve empirical design. PMID- 22306342 TI - Role of epigenetic aberrations in the development and progression of human hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers in humans. The molecular mechanisms leading to the development of HCC are extremely complicated and consist of prominent genetic, genomic, and epigenetic alterations. This review summarizes the current knowledge of the role of epigenetic aberrations, including changes in DNA methylation, histone modifications, and expression of microRNAs in the pathogenesis of HCC. It also emphasizes that identification of the underlying epigenetic alterations that drive cell transformation and promote development and progression of HCC is crucially important for understanding mechanisms of hepatocarcinogenesis, its detection, therapeutic intervention, and prevention. PMID- 22306343 TI - Suppression of the hypoxia inducible factor-1 function by redistributing the aryl hydrocarbon receptor nuclear translocator from nucleus to cytoplasm. AB - The aryl hydrocarbon receptor nuclear translocator (ARNT) heterodimerizes with hypoxia inducible factor-1alpha (HIF-1alpha), followed by upregulation of genes that are essential for carcinogenesis. We utilized a novel peptide (Ainp1) to address whether the HIF-1alpha signaling could be suppressed by an ARNT-mediated mechanism. Ainp1 suppresses the HIF-1alpha-dependent luciferase expression in Hep3B cells and this suppression can be reversed by ARNT. Ainp1 reduces the interaction between ARNT and HIF-1alpha, suppresses the formation of the HIF-1 gel shift complex, and suppresses the ARNT recruitment to the vegf promoter. These effects are partly mediated by redistribution of the nuclear ARNT contents to the cytoplasm. PMID- 22306344 TI - [Identification of components of metabolic syndrome in Mexican patients hospitalized for acute ischemic coronary syndrome: a tool for prevention]. AB - OBJECTIVE: To determine the prevalence of metabolic syndrome (MS) and its risk factors in patients with Acute Ischemic Coronary Syndrome (AICS) in a tertiary hospital. METHODS: A total of 65 patients admitted to Cardiac Intensive Care Unit with myocardial infarction or unstable angina participated. MS was diagnosed in accordance to the Adult Treatment Panel III (ATPIII) criteria. RESULTS: The total prevalence of MS was 84.6% (95% CI: 75.6 to 93.6). MS was more frequent in women, persons with obesity according to the body mass index (BMI), family background diabetes, and dyslipidemia. Phenotype predictors of MS were: BMI (OR=2.12, 95% CI: 1.24, 3.17) and familiar history of dyslipidemia (OR=0.026, 95% CI: 0.003, 0.587). CONCLUSIONS: The prevalence of MS with AICS is higher than that reported in other populations. This fact is alarming if this risk is maintained in the Mexican population. PMID- 22306345 TI - Metabotropic glutamate receptors in neurodegeneration/neuroprotection: still a hot topic? AB - Moving from early studies, we here review the most recent evidence linking metabotropic glutamate (mGlu) receptors to processes of neurodegeneration/neuroprotection. The use of knockout mice and subtype-selective drugs has increased our knowledge of the precise role played by individual mGlu receptor subtypes in these processes. Activation of mGlu1 and mGlu5 receptors may either amplify or reduce neuronal damage depending on the context and the nature of the toxic insults. In contrast, mGlu1 and mGlu5 receptors antagonists are consistently protective in in vitro and in vivo models of neuronal death. A series of studies suggest that mGlu1 receptor antagonists or negative allosteric modulators (NAMs) are promising candidates for the treatment of ischemic brain damage, whereas mGlu5 receptor NAMs, which have been clinically developed for the treatment of Parkinson's disease (PD) and l-DOPA-induced dyskinesias, protect nigro-striatal dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) toxicity in mice and monkeys. Activation of glial mGlu3 receptors promotes the formation of various neurotrophic factors, such as transforming growth factor-beta (TGF-beta), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF). Hence, selective mGlu3 receptor agonists or positive allosteric modulators (PAMs) (not yet available) are potentially helpful in the treatment of chronic neurodegenerative disorders such as PD, Alzheimer's disease (AD), and amyotrophic lateral sclerosis. Selective mGlu2 receptor PAMs should be used with caution in AD patients because these drugs are shown to amplify beta-amyloid neurotoxicity. Finally, mGlu4 receptor agonists/PAMs share with mGlu5 receptor NAMs the ability to improve motor symptoms associated with PD and attenuate nigro-striatal degeneration at the same time. No data are yet available on the role of mGlu7 and mGlu8 receptors in neurodegeneration/neuroprotection. PMID- 22306346 TI - Repeated treatment with the kappa opioid receptor agonist U69593 reverses enhanced K+ induced dopamine release in the nucleus accumbens, but not the expression of locomotor sensitization in amphetamine-sensitized rats. AB - The effects after the acute activation of the kappa opioid receptor (KOR) can be distinguished from the effect after repeated administration of KOR agonist. Here, we report the effect of repeated administration of U69593 during abstinence after amphetamine-induced locomotor sensitization. Rats were injected once daily with amphetamine for five consecutive days. From day 6 to 9, rats that developed locomotor sensitization, received once daily injection of U69593 or vehicle. On day 10, all rats were injected with a challenging dose of amphetamine and locomotor activity was measured to assess the expression of sensitization. Microdialysis studies were carried out to assess dopamine extracellular levels in NAc. Rats that develop and express horizontal locomotor sensitization to amphetamine show increased dopamine release in the NAc induced by high K(+). The repeated treatment with U69593 reverses the sensitized depolarization-stimulated dopamine release in the NAc, but not the expression of locomotor sensitization induced by amphetamine. Thus, repeated activation of KORs during early amphetamine withdrawal dissociates the behavioral responses and the neurochemical responses that accompany the expression of sensitization to amphetamine. PMID- 22306347 TI - The effects of corticotropin-releasing factor and the urocortins on hypothalamic gamma-amino butyric acid release--the impacts on the hypothalamic-pituitary adrenal axis. AB - Corticotropin-releasing factor (CRF) and the urocortins (UCNs) are structurally and pharmacologically related neuropeptides which regulate the endocrine, autonomic, emotional and behavioral responses to stress. CRF and UCN1 activate both CRF receptors (CRFR1 and CRFR2) with CRF binding preferentially to CRFR1 and UCN1 binding equipotently to both receptors. UCN2 and UCN3 activate selectively CRFR2. Previously an in vitro study demonstrated that superfusion of both CRF and UCN1 elevated the GABA release elicited by electrical stimulation from rat amygdala, through activation of CRF1 receptors. In the present experiments, the same in vitro settings were used to study the actions of CRF and the urocortins on hypothalamic GABA release. CRF and UCN1 administered in equimolar doses increased significantly the GABA release induced by electrical stimulation from rat hypothalamus. The increasing effects of CRF and UCN1 were inhibited considerably by the selective CRFR1 antagonist antalarmin, but were not influenced by the selective CRFR2 antagonist astressin 2B. UCN2 and UCN3 were ineffective. We conclude that CRF1 receptor agonists induce the release of GABA in the hypothalamus as well as previously the amygdala. We speculate that CRF induced GABA release may act as a double-edged sword: amygdalar GABA may disinhibit the hypothalamic CRF release, leading to activation of the hypothalamic-pituitary-adrenal axis, whereas hypothalamic GABA may inhibit the hypothalamic CRF release, terminating this activation. PMID- 22306348 TI - Regulation of neurokine receptor signaling and trafficking. AB - Leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) are neurally active cytokines, or neurokines. LIF signals through a receptor consisting of gp130 and the low affinity LIF receptor (LIFR), while the CNTF receptor consists of gp130, LIFR, and the low affinity CNTF receptor (CNTFR). Ser1044 of the LIFR is phosphorylated by Erk1/2 MAP kinase. Stimulation of neural cells with growth factors which strongly activate Erk1/2 decreases LIF-mediated signal transduction due to increased degradation of the LIFR as a consequence of Erk1/2-dependent phosphorylation of the receptor at Ser1044. The gp130 receptor subunit is phosphorylated, at least in part by calmodulin-dependent protein kinase II, at Ser782, which is adjacent to a dileucine internalization motif. Ser782 appears to negatively regulate cytokine receptor expression, as mutagenesis of Ser782 results in increased gp130 expression and cytokine-induced neuropeptide gene transcription. The LIFR and gp130 are transmembrane proteins, while CNTFR is a peripheral membrane protein attached to the cell surface via a glycosylphosphatidylinositol tail. In unstimulated cells, CNTFR but not LIFR and gp130 is localized to detergent-resistant lipid rafts. Stimulation of cells with CNTFR causes translocation of LIFR and gp130 into the lipid rafts, while stimulation with LIF does not induce receptor translocation, raising the possibility that CNTF could induce different patterns of signaling and/or receptor trafficking than caused by LIF. We used a compartmentalized culture system to examine the mechanisms for retrograde signaling by LIF and CNTF from distal neurites to the cell bodies of mouse sympathetic neurons. Stimulation with neurokines of the distal neurites of sympathetic neurons grown in a compartmentalized culture system resulted in the activation and nuclear translocation of the transcription factor Stat3. Retrograde signaling required Jak kinase activity in the cell body but not the distal neurites, and could be blocked by inhibitors of microtubule but not microfilament function. The results are consistent with a signaling endosomes model in which the ctyokine/receptor complex is transported back to the cell body where Stat3 is activated. While both LIF and CNTF mediate retrograde activation of Stat3, the kinetics for retrograde signaling differ for the two neurokines. PMID- 22306349 TI - Clinical value of circulating endothelial cell detection in oncology. AB - Given the importance of tumor vasculature in tumor biology and as a target for treatment, there is an increasing need for biomarkers that reflect effects impacting tumor vasculature accurately. Circulating endothelial cells (CECs) increase in number as a result of vascular damage in cancer and several other diseases. CEC count constitutes a promising tool for monitoring disease activity with potential to assess prognosis and response to treatment. Here, we address the current state-of-the-art of CEC enumeration as a biomarker in clinical oncology. We focus on technical issues concerning CEC detection, review results from clinical studies and explore future potential applications. PMID- 22306350 TI - Monoclonal antibodies for chronic refractory asthma and pipeline developments. AB - Patients with severe asthma suffer persistent symptoms and/or frequent exacerbations despite high-intensity treatment. Their severe unrelenting symptoms have a huge impact on healthcare resources owing to frequent hospital admissions and requirement for intensive treatments. Consequently, there is an undeniable need for more-effective and safer medications. Expanding knowledge of innate and adaptive immune responses is leading to the development of novel therapies for severe asthma. Herein, we review efficacy and safety data from human clinical trials of monoclonal antibodies that are approved or under investigation for use in asthma. Future drug candidates directed at key targets and the specific role of monoclonal antibodies in distinctively targeted sub-populations of severe asthmatics will be also discussed. PMID- 22306351 TI - Analysis of Streptococcus pneumoniae secreted antigens by immuno-proteomic approach. AB - Streptococcus pneumoniae is an important human pathogen that causes a variety of diseases in both adults and children, such as pneumonia, bacteremia, meningitis, otitis media, and sinusitis. Despite their clinical importance, to date, there have been few proteomic studies of these strains for screening of virulence factors or diagnostic markers. In the present study, secreted proteins (secretome) of Streptococcus pneumoniae strains were enriched using ammonium sulfate precipitation and identified by the shotgun proteomic method using 1 dimensional electrophoresis liquid chromatography-mass spectrometry/mass spectrometry analysis. Characterization of the identified proteins revealed that 17.8% (42) of the secreted proteins possessed signal peptides. Twenty-one secreted proteins belonged to the extracellular group, and 4 secreted proteins belonged to the cell wall group. Well-known virulence factors (PrtA, PspC, PsaA, PbpA, PhtD, AmiA, ZmpB, Eno, and Ply) were included in the secreted protein fraction. Western blotting using antiserum against secreted protein mixtures showed that Gsp-781, Sphtra, NagA, PhtD, ZmpB, and Eno were strongly immunogenic. Our data suggest that the immuno-proteomic approach is a useful method for high throughput identification of secreted proteins and screening of candidate vaccine antigens or diagnostic markers. Gsp-781 is introduced as a novel secreted antigen of Streptococcus pneumoniae. PMID- 22306352 TI - Impact of yeast-bacteria coinfection on the detection of Candida sp. in an automated blood culture system. AB - Invasive candidiasis remains a major cause of morbidity and mortality. It is now well known that an early diagnosis contributes to the patients' outcome. Blood cultures, which are the first-line test in case of bloodstream infection suspicion, can be carried out using fungus-selective medium (containing antibiotics) or standard microorganism medium allowing both bacterial and fungal growth. Some patients can suffer from polymicrobial sepsis involving bacteria and yeasts, so we decided to investigate in blood cultures the influence of the presence of bacteria on fungal development. Simulated blood cultures were performed using Candida albicans or C. glabrata coincubated with Escherichia coli or Staphylococcus aureus at different concentrations. The results showed that, in a standard microorganism medium, bacterial growth could hide the fungal development. Thus, in patients at risk of invasive candidiasis, the use of a specific fungal medium could improve the diagnosis and allow an earlier efficient antifungal treatment. PMID- 22306353 TI - Identification of Henosepilachna vigintioctomaculata (Coleoptera: Coccinellidae) midgut putative receptor for Bacillus thuringiensis insecticidal Cry7Ab3 toxin. AB - Bt WZ-9 strain, containing a single Cry7Ab3 toxin, had effective insecticidal activity against larvae of Henosepilachna vigintioctomaculata. By incubation with larvae midgut homogenate and trypsin in vitro, 130 kDa Cry7Ab3 protoxin was degraded into the ~75 kDa proteinase-resistant fragments. In vivo analysis, 130 kDa Cry7Ab3 protoxin was also processed into ~75 kDa fragment. Histopathological observations indicated that Cry7Ab3 ingestion by H. vigintioctomaculata larvae causes acceleration in the blebbing of the midgut epithelium cells into the gut lumen and eventual lysis of the epithelium cells resulting in larval death. A ligand blotting experiment demonstrated that Cry7Ab3 toxin bound a 220 kDa BBMV protein. This receptor protein was identified as cadherin by matrix assisted laser desorption-time of flight-mass spectrometry (MALDI-TOF-MS). The cadherin protein may be the receptor of Cry7Ab3. The data obtained may contribute to a better understanding of the mechanism of Cry7Ab3 toxin against H. vigintioctomaculata larvae. PMID- 22306354 TI - Excess copper induced oxidative stress and response of antioxidants in rice. AB - To investigate the effects of copper (Cu), rice plant (Oryza sativa. L. var. MSE 9) was treated with different Cu concentrations (0, 10, 50 and 100 MUM) for 5 days in hydroponic condition. Gradual decrease in shoot and root growth was observed with the increase of Cu concentration and duration of treatment where maximum inhibition was recorded in root growth. Cu was readily absorbed by the plant though the maximum accumulation was found in root than shoot. Hydrogen peroxide (H(2)O(2)) production and lipid peroxidation were found increased with the elevated Cu concentration indicating excess Cu induced oxidative stress. Antioxidant enzymes superoxide dismutase (SOD), guaiacol peroxidase (GPX) and ascorbate peroxidase (APX) and glutathione reductase (GR) were effectively generated at the elevated concentrations of Cu though catalase (CAT) did not show significant variation with respect to control. Ascorbate (ASH), glutathione (GSH) and proline contents were also increased in all the Cu treated plants compared with the control. SOD isoenzyme was greatly affected by higher concentration of Cu and it was consistent with the changes of the activity assayed in solution. The present study confirmed that excess Cu inhibits growth, induced oxidative stress by inducing ROS formation while the stimulated antioxidative system appears adaptive response of rice plant against Cu induced oxidative stress. Moreover proline accumulation in Cu stress plant seems to provide additional defense against the oxidative stress. PMID- 22306355 TI - Oligomerization studies show that the kinase domain of the tomato pollen receptor kinase LePRK2 is necessary for interaction with LePRK1. AB - LePRK1 and LePRK2 are two pollen-specific receptor-like kinases from Solanum lycopersicum that are involved in signaling during pollen-pistil communication. Previously, we showed that both proteins interact in pollen and when expressed in yeast. We also showed that pollen tube length was regulated by phosphorylation of specific residues in the juxtamembrane domain of LePRK2. To determine the domains responsible for the interaction between LePRK1 and LePRK2, we constructed a series of deletions, expressed them in yeast and determined their association by co-immunoprecipitation assays. We show that deletions containing extracellular domains of LePRK1 and LePRK2 were glycosylated in yeast and were sufficient for interaction with the corresponding full-length receptor. The juxtamembrane domain of LePRK1 was sufficient for its interaction with LePRK2, whereas LePRK2 required its kinase domain for interaction with LePRK1. These findings suggest a role for the juxtamembrane domain of LePRK2 in mediating intracellular dimerization and thus receptor kinase phosphorylation. PMID- 22306356 TI - Antibodies to Plasmodium circumsporozoite protein (CSP) inhibit sporozoite's cell traversal activity. AB - Plasmodium sporozoites are deposited in the skin of the mammalian host by Anopheles mosquitoes. To continue the life cycle, the sporozoites have to invade the host's hepatocytes, where they transform into exoerythrocytic forms (EEFs) inside a parasitophorous vacuole. During their route from the skin to the liver, the parasites traverse the capillary epithelium in the dermis to enter the blood circulation, and cross the endothelium of liver sinusoids to enter the parenchyma. Cell traversal by sporozoites is usually measured by quantifying dyes that enter or are released from cells during incubation with salivary gland sporozoites. These methods do not distinguish cell traversal from cell wounding. Here we validate an assay that quantifies cell traversal of sporozoites through monolayers of MDCK cells that form tight junctions. We compared cell traversal of wt sporozoites and of parasites lacking the Type I membrane protein TLP (TRAP like protein) previously implicated in cell traversal. We provide direct evidence that TLP ko sporozoites are defective in cell traversal and that they are retained inside the MDCK cytoplasm. We then used the MDCK assay to study the effect of a monoclonal antibody (3D11) to the circumsporozoite protein (CSP) on the parasite's cell traversal. We show that 3D11 inhibits cell traversal at nanomolar concentrations. We conclude that antibodies elicited by CSP-based vaccines are likely to inhibit the migration of sporozoites from the skin to the liver. PMID- 22306357 TI - Influence of NK cell magnetic bead isolation methods on phenotype and function of murine NK cells. AB - Natural killer (NK) cells are a promising tool for cell therapy due to their capacity to lyse tumor cells without prior activation and their influence on the innate as well as the adaptive immunity. To characterize distinct NK cell populations, it is important to find a reliable isolation method. We investigated separation methods for NK cell isolation by magnetic bead labeling. There are three commonly used different MACS protocols to isolate NK cells from murine spleen: CD49b (DX5) MicroBeads, the NK Cell Isolation Kit and a separation method which is based on a positive selection for NKp46 expressing cells. Interestingly, we found a significant difference of NK cell purities depending on the mouse strains and the purification protocol used. We observed a significantly higher level of purity and yield of NK cells by preparations from Balb/c splenocytes. In this study, we modified the negative selection protocol and adapted it to C57Bl/6 mice to obtain equal purity, viability and yields of NK cells in the different mouse strains. Moreover, we optimized the NKp46 NK cell selection method by addition of a B cell depletion step. To our knowledge, this is the first report that has directly compared and essentially modified the different NK cell purification strategies in parallel, both in C57Bl/6 and Balb/c mouse strains. Altogether, these results are a basic prerequisite for the further development of NK cell therapy protocols in murine in vivo models. PMID- 22306358 TI - Validation and quality control of ELISAs for the use with human saliva samples. AB - Enzyme-linked immunosorbent assays (ELISAs) have proven to be a powerful tool for fast and reliable sample analysis, in both clinical diagnostics and in research. Most assays are now available for use with a range of different analytical fluids, including serum, plasma or urine. In recent years, saliva has drawn attention as a potentially valuable diagnostic fluid; however few ELISAs have been validated for use with saliva, or their validation is often incomplete. Saliva has a number of different physical characteristics than, for example, cell culture medium or serum and assuming an ELISA which works well with serum samples will also do so with saliva potentially could lead to erroneous data and conclusions. In this report, we provide a detailed protocol to validate any ELISA for use with saliva samples and show the results of validation procedures for 13 ELISAs for using saliva. Our findings suggest that the majority of ELISAs work reliably with saliva, even if the assay was not specifically designed for this biological fluid. However, we also report a few cases where recovery or intra-and inter-assay variations were unexpectedly high, emphasising the importance of performing a validation procedure for each assay before using it with saliva to ensure accurate and reliable data. PMID- 22306359 TI - Twenty-four new human cases of cutaneous leishmaniasis due to Leishmania killicki in Metlaoui, southwestern Tunisia: probable role of Phlebotomus sergenti in the transmission. AB - Metlaoui district in the South-west of Tunisia is a classical focus of cutaneous leishmaniasis (CL) due to Leishmania major. Since 2005, a single case of CL due to L. killicki has been reported. We report twenty four human cases due to this parasite, affecting men and women from 2 to 70 years old. Leishmania killicki have been typed using molecular techniques: polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) and gene sequencing. Four strains from patients have been successfully cultured on NNN medium and isoenzymatically typed as L. killicki MON-8. Our results strongly suggests that Metlaoui is a new L. killicki focus with a stable transmission cycle. Sand flies fauna in the same focus was also studied. 1400 Phlebotomine sand flies (785 males/615 females) have been caught during an entomological survey. Leishmania major DNA has been found in one P. papatasi female, the most abundant species, whereas L. killicki DNA has been found in one Phlebotomus sergenti female emphasizing the probable role of this species as vector of this zoonotic parasite. PMID- 22306360 TI - [Pediatric poisoning with triptans: review of cases in the Lille poison center between 2000 and 2010]. AB - BACKGROUND AND OBJECTIVE: Triptans are recommended to treat acute migraine. Pediatric data remain insufficient for making decisions in cases of triptan poisoning. Consequently, hospitalization is often warranted as a precautionary measure. This study aims to more accurately estimate the risks incurred when a young child ingests triptan tablets. MAIN OUTCOME MEASURES: This study reviewed all cases of acute triptan poisoning listed by the Lille poison center between January 2000 and December 2009 in children younger than 6 years. Cases with certain ingestion, no drug interactions, and no other known etiology were selected. The gravity of each case was estimated by the poisoning severity score and follow-up was conducted by phone. RESULTS: A cohort of 84 patients was collected: 6% were lost to follow-up. The mean intake was 1.22 tablets (range, 0.25-6), for the most part zolmitriptan (64.2%), eletriptan (14.3%) and naratriptan (14.3%). Fifty-nine children (74.5%) were admitted to the hospital and 20 children monitored at home. The majority received evacuation or adsorbing treatment. Symptoms were not frequent (13%) and were well tolerated, in particular on the hemodynamic level (ten cases of PSS1). The adverse events observed were tachycardia (4 cases), arterial hypertension (1 case), dyspnea (2 cases), drowsiness (2 cases), marbling of the extremities (1 case), vomiting (3 cases), and digestive pain (1 case). The 2 cases of dyspnea, induced by 2.5mg and 7.5mg of zolmitriptan, respectively, were associated with cardiovascular symptoms and were left untreated. According to its pharmacological action, the potential risk of a serotoninergic syndrome is a concern with triptan intake. No severe complication was recorded, so based on this study, our guidelines were updated. The response should be less alarmist, but a watchful attitude should be retained. Hospitalization should not be systematic, but focused on the patient's cardiac history, the dose, and the symptomatology. If the child remains at home, specific action should be managed: an adsorbing treatment and close monitoring by phone remain essential. PMID- 22306361 TI - [Allergic march in children, from rhinitis to asthma: management, indication of immunotherapy]. AB - Allergic rhinitis (AR) is a common IgE dependent disorder. AR is maybe one of the steps of the allergic march, which starts with atopic dermatitis and food allergy and includes atopic asthma. AR and asthma are frequently associated. AR is frequently under-diagnosed and undertreated although it affects quality of life and school performance. Management of AR depends on its severity and will associate environmental control (best guided by environmental investigation and skin testing of specific IgE antibodies), pharmacotherapy (with antihistamines and intranasal corticosteroids as first line drugs). At present allergen immunotherapy is considered in patients with severe AR, insufficiently controlled by pharmacotherapy and who demonstrate specific IgE antibodies to relevant allergens. Sublingual immunotherapy is well tolerated. Only immunotherapy with the right allergens has the potential to alter the natural history of the allergic march, by preventing the development of new allergen sensitizations and reducing the risk for the subsequent development of asthma. This fact might extend the indications of specific allergen immunotherapy. Patients (and parents) education is of utmost importance in the management of allergic disorders. PMID- 22306362 TI - Diacylglycerol-containing oleic acid induces increases in [Ca(2+)](i) via TRPC3/6 channels in human T-cells. AB - Though most of the studies have focused on the effects of free fatty acids on T cell activation, fatty acids incorporated into plasma membrane phospholipids may also affect cell signaling via diacylglycerol (DAG), generally produced by phospholipid hydrolysis. In the present study, we have synthesized a DAG containing oleic acid and studied its implication in the modulation of calcium signaling in human Jurkat T-cells. 1-palmitoyl-2-oleoyl-sn-glycerol (POG) induced a dose-dependent increase in [Ca(2+)](i). This effect was due to the presence of oleic acid at the sn-2 position as no differences were observed between POG and 1 stearoly-2-oleoyl-sn-glycerol (SOG). However, the substitution of oleic acid with arachidonic acid at the sn-2 position of the DAG moiety exerted a different response on the increases in [Ca(2+)](i) in these cells. POG-evoked increases in [Ca(2+)](i) were not due to its metabolites. Furthermore, POG-induced increases in [Ca(2+)](i) were due to the opening of TRPC3/TRPC6 channels as silencing of TRPC3 and TRPC6 genes by shRNA abolished calcium entry. Moreover, disruption of lipid rafts with methyl-beta-cyclodextrin completely abolished POG-evoked increases in [Ca(2+)](i). In conclusion, our results demonstrate that oleic acid can influence T-lymphocyte functions, in the conjugated form of DAG, via opening TRPC3/6 channels. PMID- 22306363 TI - Retinoic acid increases hypoxia-inducible factor-1alpha through intracrine prostaglandin E(2) signaling in human renal proximal tubular cells HK-2. AB - We have previously shown in HK-2 cells that ATRA (all-trans-retinoic acid) up regulates HIF-1alpha (hypoxia-inducible factor-1alpha) in normoxia, which results in increased production of renal protector VEGF-A (vascular endothelial growth factor-A). Here we investigated the role of COXs (cyclooxygenases) in these effects and we found that, i) ATRA increased the expression of COX-1 and COX-2 mRNA and protein and the intracellular levels (but not the extracellular ones) of PGE(2). Furthermore, inhibitors of COX isoenzymes blocked ATRA-induced increase in intracellular PGE(2), HIF-1alpha up-regulation and increased VEGF-A production. Immunofluorescence analysis found intracellular staining for EP1-4 receptors (PGE(2) receptors). These results indicated that COX activity is critical for ATRA-induced HIF-1alpha up-regulation and suggested that intracellular PGE(2) could mediate the effects of ATRA; ii) Treatment with PGE(2) analog 16,16-dimethyl-PGE(2) resulted in up-regulation of HIF-1alpha and antagonists of EP1-4 receptors inhibited 16,16-dimethyl-PGE(2)- and ATRA-induced HIF-1alpha up-regulation. These results confirmed that PGE(2) mediates the effects of ATRA on HIF-1alpha expression; iii) Prostaglandin uptake transporter inhibitor bromocresol green blocked the increase in HIF-1alpha expression induced by PGE(2) or by PGE(2)-increasing cytokine interleukin-1beta, but not by ATRA. Therefore only intracellular PGE(2) is able to increase HIF-1alpha expression. In conclusion, intracellular PGE(2) increases HIF-1alpha expression and mediates ATRA-induced HIF-1alpha up-regulation. PMID- 22306364 TI - Ordering of ceramide formation and caspase-9 activation in CD95L-induced Jurkat leukemia T cell apoptosis. AB - Ceramide, a biologically active sphingolipid in cell death signaling, accumulates upon CD95L treatment, concomitantly to apoptosis induction in Jurkat leukemia T cells. Herein, we show that ceramide did not increase in caspase-8 and -10-doubly deficient Jurkat cells in response to CD95L, indicating that apical caspases are essential for CD95L-triggered ceramide formation. Jurkat cells are typically defined as type 2 cells, which require the activation of the mitochondrial pathway for efficient apoptosis induction in response to CD95L. Caspase-9 deficient Jurkat cells significantly resisted CD95L-induced apoptosis, despite ceramide accumulation. Knock-down of sphingomyelin synthase 1, which metabolizes ceramide to sphingomyelin, enhanced (i) CD95L-triggered ceramide production, (ii) cytochrome c release from the mitochondria and (iii) caspase-9 activation. Exogenous ceramide-induced caspase-3 activation and apoptosis were impaired in caspase-9-deficient Jurkat cells. Conversely, caspase-9 re-expression in caspase 9-deficient Jurkat cells restored caspase-3 activation and apoptosis upon exogenous ceramide treatment. Collectively, our data provide genetic evidence that CD95L-triggered endogenous ceramide increase in Jurkat leukemia T cells (i) is not a mere consequence of cell death and occurs mainly in a caspase-9 independent manner, (ii) is likely involved in the pro-apoptotic mitochondrial pathway leading to caspase-9 activation. PMID- 22306365 TI - A small-molecule inhibitor of deubiquitinating enzyme USP14 inhibits Dengue virus replication. AB - The ubiquitin-proteasome system (UPS) is a key player in maintaining cellular protein homeostasis and is associated with various human diseases, including neurodegenerative disorders, cancer, and infectious diseases. Viruses from several families reprogram the UPS to make the cellular environment conducive to viral replication, and inhibition of the UPS interferes with viral propagation. Here we show that IU1, a small-molecule inhibitor of the proteasome-associated deubiquitinating enzyme USP14, inhibits replication of several flaviviruses. IU1 has been shown to enhance proteasome activity, an effect that may underlie its influence on flavivirus propagation. Inhibition of dengue virus replication was more pronounced than other flaviviruses used in the study. These results open new targets for therapeutic intervention against viruses from multiple families. PMID- 22306366 TI - [A recurrent cutaneous fistula secondary to the migration of a clip: report of a complication of tubal sterilization]. AB - The tubal sterilization is a safe and recognized sterilization method. The complications of this intervention are rare and mainly concern failure of surgical procedure or clip migrations. We report the first case of spontaneous migration of a clip behind the psoas followed by a chronic osteitis. PMID- 22306367 TI - Cyclooxygenase-2 contributes to VX-induced cell death in cultured cortical neurons. AB - The link between cell death and increased cyclooxygenases-2 (COX-2) activity has not been clearly established. In this study, we examined whether COX-2 activation contributed to the mechanism of neurotoxicity produced by an organophosphorous nerve agent in cultured rat cortical neurons. Exposure of neuronal cells to the nerve agent, VX resulted in an increase in COX enzyme activity in the culture media. A concentration dependent increase in the activity levels of COX-2 enzyme was observed while there was little to no effect on COX-1. In addition, COX-2 mRNA and protein levels increased several hours post-VX exposure. Pre-treatment of the cortical cells with the COX-2 selective inhibitor, NS 398 resulted in a decrease in both the enzyme activity and prostaglandin (PGE(2) and PGF(2alpha)) release, as well as in a reduction in cell death. These findings indicate that the increase in COX-2 activity may contribute to the mechanism of VX-induced neurotoxicity in cultured rat cortical neuron. PMID- 22306368 TI - A case-control study of polymorphisms in xenobiotic and arsenic metabolism genes and arsenic-related bladder cancer in New Hampshire. AB - Arsenic is associated with bladder cancer risk even at low exposure levels. Genetic variation in enzymes involved in xenobiotic and arsenic metabolism may modulate individual susceptibility to arsenic-related bladder cancer. Through a population-based case-control study in NH (832 cases and 1191 controls), we investigated gene-environment interactions between arsenic metabolic gene polymorphisms and arsenic exposure in relation to bladder cancer risk. Toenail arsenic concentrations were used to classify subjects into low and high exposure groups. Single nucleotide polymorphisms (SNPs) in GSTP1, GSTO2, GSTZ1, AQP3, AS3MT and the deletion status of GSTM1 and GSTT1 were determined. We found evidence of genotype-arsenic interactions in the high exposure group; GSTP1 Ile105Val homozygous individuals had an odds ratio (OR) of 5.4 [95% confidence interval (CI): 1.5-20.2; P for interaction=0.03] and AQP3 Phe130Phe carriers had an OR=2.2 (95% CI: 0.8-6.1; P for interaction=0.10). Bladder cancer risk overall was associated with GSTO2 Asn142Asp (homozygous; OR=1.4; 95% CI: 1.0-1.9; P for trend=0.06) and GSTZ1 Glu32Lys (homozygous; OR=1.3; 95% CI: 0.9-1.8; P for trend=0.06). Our findings suggest that susceptibility to bladder cancer may relate to variation in genes involved in arsenic metabolism and oxidative stress response and potential gene-environment interactions requiring confirmation in other populations. PMID- 22306369 TI - Farmers' exposure to herbicides in North Italy: assessment under real-life conditions in small-size rice and corn farms. AB - Although rice and corn are two main cash crops in Lombardy (North Italy) and their cultivation involves several thousands of farmers, risk assessment of pesticide exposure is rarely done, especially in small and medium sized enterprises. With the use of pads for environmental monitoring (OECD protocol), of pre- and post-exposure 24h urine collection for biological monitoring and of hand wash for hands' exposure, we measured the exposure of 28 agricultural workers to propanil and terbuthylazine in real-life working conditions. In propanil applicators, median daily exposure on the clothes was 73.5MUmol per worker, while the exposure on the skin was 22.4MUmol. For terbuthylazine, these exposures were 37.2MUmol and 0.86MUmol per worker, respectively. Median excretion of the propanil metabolite (3,4-dichloroaniline) after exposure was 84nmol in 24h urine, and 13nmol for the metabolite of terbuthylazine. Risk assessment performed by comparing to the AOELs of the applied active ingredients with an estimated internal dose, obtained based on the measured levels of skin and hand exposure and the percentage of dermal absorption of the active ingredients considered showed that 4 propanil workers, and no terbuthylazine workers, were overexposed. Our study helps define and confirm relationships between different exposure determinants, which can be used in the development of tools for risk assessment of exposure to pesticides in small and medium sized enterprises. PMID- 22306370 TI - The increasing significance of biomonitoring for pesticides and organic pollutants. PMID- 22306371 TI - Retinal breaks in small-gauge pars plana vitrectomy. AB - PURPOSE: To determine the frequency of peripheral iatrogenic retinal breaks in eyes undergoing small-gauge pars plana vitrectomy. DESIGN: Prospective, single center, noncomparative interventional case series. METHODS: A consecutive series of patients that underwent 23- or 25-gauge vitrectomy between July 2010 and the end of October 2010 were included in the study. We excluded patients with retinal detachment, dislocated crystalline lens from complicated cataract surgery, endophthalmitis, and previous history of eye trauma or vitrectomy. We recorded prospectively the frequency of all retinal breaks noted during surgery of patients undergoing 23- or 25-gauge vitrectomy. The indications for vitreoretinal surgery were recorded, as were the location of retinal breaks, the presence or absence of an intact posterior hyaloid, status of lens, method of retinopexy, and use of a tamponade, together with the onset of a rhegmatogenous retinal detachment during the 3-month follow-up interval. Main outcome was rate of entry site breaks in small-gauge vitrectomy. RESULTS: We included 184 patients in this study. The mean age was 65.6 years (SD 13.2) and 46% were male. Retinal breaks occurred in 29 patients (15.7%) but breaks in only 6 (3.2%) were deemed to be related to the sclerotomies. Entry site breaks were not linked to the gauge of the instruments, but retinal breaks were more common in 23-gauge surgeries, although this was not statistically significant. One rhegmatogenous retinal detachment occurred in the postoperative period. CONCLUSIONS: Entry site retinal breaks are not common in small-gauge vitrectomy. PMID- 22306372 TI - Everything you wanted to know about selecting the "right" Actigraph accelerometer cut-points for youth, but...: a systematic review. AB - OBJECTIVES: The purpose of this study is to provide an overview of the evidence on the calibration of ActiGraph accelerometers to quantify moderate-to-vigorous physical activity (MVPA) for youth through the use of cut-points and describe the independent validation studies comparing the accuracy of the developed cut-points to a criterion measure. DESIGN: A systematic review. METHODS: Studies were identified that: (a) developed ActiGraph accelerometer cut-points for children and youth (calibration study); or (b) performed an independent validation of already established cut-points (validation study). Both calibration studies and independent validation studies were retrieved through a systematic search of online databases. According to proposed guidelines for designing accelerometer calibration studies, each calibration study was evaluated on the following criteria: quality of a criterion measure employed; epoch length; inclusion of a variety of activities; and sample size. RESULTS: A total of 11 calibration studies were identified. Two studies met all four criteria for a calibration study. A total of 4 independent validation studies were identified. Three of them reported that no cut-points accurately classified moderate-to-vigorous physical activity (MVPA) across all ranges of physical activity intensity levels in comparison to a criterion measure. The fourth study reported two sets of cut points that under laboratory conditions, accurately classified moderate-to vigorous physical activity (MVPA) compared to indirect calorimetry. CONCLUSIONS: Limited evidence suggests that two sets of cut-points correctly classify ActiGraph counts into moderate-to-vigorous physical activity (MVPA). However, limitations with calibration and validation studies indicate greater efforts aimed at designing high quality studies are needed to confirm these findings. PMID- 22306373 TI - Juvenile but not adult methamphetamine exposure improves performance in the Morris Water Maze in male rats. AB - Early exposure to psychostimulants has been found to lead to long-lasting effects on cognitive processes. Our lab has previously reported that juvenile male rats administered methamphetamine showed improved performance in a spatial navigation task when tested in adulthood (McFadden and Matuszewich, 2007). What is not known, however, is if these effects are specific to the developing rat, or if a similar methamphetamine protocol given to adult rats would lead to an equally beneficial long-term change in spatial cognition. In the current study, male rats were given 1 daily injection of 2mg/kg methamphetamine or saline for 15 days during either preadolescence (PD20-34) or adulthood (PD70-84). Approximately 45 days after treatment, all rats then underwent 5 days of place training in the Morris water maze at a time when juvenile rats reached adulthood. Similar to previous findings, juvenile rats exposed to repeated methamphetamine displayed shorter latencies and distances to reach the platform throughout training compared to saline-treated rats. The juvenile rats treated with methamphetamine also swam shorter distances and had faster latencies to the hidden platform compared to adult methamphetamine-treated rats. There were no significant differences in rats treated in adulthood with methamphetamine compared to saline treated rats. Likewise, there were no effects of prior methamphetamine treatment or age on matching-to-place trials or visible platform trials. Overall, the results show that repeated methamphetamine exposure can selectively improve spatial learning in adult male rats when administered during preadolescence, but does not significantly affect spatial learning when administered in adulthood. Furthermore, the current findings demonstrate the unique susceptibility of the developing brain to drugs that modulate dopaminergic activity, as well as the long-term behavioral impact of exposure at critical ages. PMID- 22306374 TI - Expression of coat proteins changes during postnatal development in selected areas of the rat brain. AB - It is well known that clathrin-mediated endocytosis is crucial for the normal functioning and integrity of neurons in the central nervous system. In this study we attempted to correlate the expression of coat proteins with development in different areas of rat brain. By Western blot, we studied the expression of AP-2, GGA1 and GGA2 in striatum, cerebellum, brain stem, cerebral cortex and hippocampus of newborn rats and during post-natal development; 5, 15, 30, 60, 90 or 150 days after birth. We observed that the expression of the alpha2 subunit of AP-2 increased substantially between the 15th and 30th day after birth in all areas studied, excepting the cerebellum and cortex. On the other hand, the expression of the alpha1 subunit does not change significantly during the development in any of the areas under study. We also noted that the expression of the MU2 subunit did not follow the pattern of alpha2 during development. In general terms, the expression of GGA1 and GGA2 followed a similar pattern to that of AP-2, although these proteins increased significantly in the cerebral cortex from the 15th day after birth. Moreover, presenilin-1, a protein associated with aging and neurodegeneration, shows an expression pattern similar to coat proteins in the striatum and cortex. These results suggest that proteins that conform the intracellular transport machinery in the brain cells seems to accompany development, according to the maturation of the different brain areas. PMID- 22306375 TI - Phase I dose finding studies of an adjuvanted Clostridium difficile toxoid vaccine. AB - Fifty healthy adult (18-55 years) and 48 elderly (>= 65 years) volunteers were randomized to receive a candidate Clostridium difficile toxoid vaccine (2 MUg, 10 MUg, or 50 MUg) or placebo on Days 0, 28, and 56. No volunteer receiving placebo seroconverted. For toxin A, seroconversion by Day 56 (post-dose 2) was observed in 100% of volunteers aged 18-55 years in all dose groups and in 50%, 89%, and 100% of elderly participants in the 2 MUg, 10 MUg, and 50 MUg dose groups, respectively. For both age groups, seroconversion for toxin B was lower than toxin A. There were no safety concerns. PMID- 22306377 TI - Helicobacter infection induces podosome assembly in primary hepatocytes in vitro. AB - Helicobacter pylori (H. pylori) infection may contribute to many extragastric diseases including liver cirrhosis and hepatocellular carcinoma. However, the exact mechanism by which H. pylori induces the liver damage is largely unknown. We used cultured mouse primary hepatocytes as an in vitro model to investigate different aspects of liver physiology and pathology. In this study, we show that primary hepatocytes are able to assemble actin-based cytoskeletal structures called podosomes at the ventral plasma membrane. These structures are positive for podosome markers such as cortactin, vinculin and integrins and comprise proteolytic potential. Infection with the pathogen H. pylori further stimulates the formation of podosomes in primary hepatocytes. The use of pharmacological inhibitors reveals that this response is mediated, at least in part, by TGFbeta, a cytokine known to regulate podosome formation in endothelial cells. Similar results are obtained with the hepatoma cell line Huh7. Podosome formation is associated with increased hepatocyte degrading capacities but also with reduced cell motility. Therefore, podosome assembly translates into hepatocyte malfunction. Our study supports the hypothesis that hepatocytes can also assemble podosomes under pathological conditions in vivo. PMID- 22306378 TI - The syncytial visceral and somatic musculature develops independently of beta3 Tubulin during Drosophila embryogenesis, while maternally supplied beta1-Tubulin is stable until the early steps of myoblast fusion. AB - Microtubules are necessary for fusion and elongation of vertebrate muscle cells. In Drosophila, several isoforms of beta-Tubulin, the functional subunit of microtubules, are expressed in different tissues of the developing embryo, while solely the beta3-Tubulin isoform is detected in large amounts during differentiation of the somatic and visceral musculature. Here we show the unexpected result that all mesodermal tissues develop correctly in beta3-Tubulin loss of function mutants. Furthermore, we show that beta2-Tubulin transcripts are not detectable in embryos and an exceptional zygotic beta1-Tubulin expression in beta3-Tubulin mutants cannot be observed. Nevertheless, a maternally contributed beta1-Tubulin-GFP fusion protein (from protein trap collection, Buszczak et al., 2007, Genetics 175, 1505-1531) acts in a dominant negative way, disturbing embryonic development from early stages on. This effect can be observed to the same extent in a zygotic beta3-Tubulin mutant situation. Our results indicate that the maternally supplied beta1-Tubulin based microtubule network is sufficient for myoblast fusion, myotube elongation and sarcomere formation both during visceral and somatic muscle development in Drosophila embryogenesis. PMID- 22306376 TI - Design considerations for liposomal vaccines: influence of formulation parameters on antibody and cell-mediated immune responses to liposome associated antigens. AB - Liposomes (phospholipid bilayer vesicles) are versatile and robust delivery systems for induction of antibody and T lymphocyte responses to associated subunit antigens. In the last 15 years, liposome vaccine technology has matured and now several vaccines containing liposome-based adjuvants have been approved for human use or have reached late stages of clinical evaluation. Given the intensifying interest in liposome-based vaccines, it is important to understand precisely how liposomes interact with the immune system and stimulate immunity. It has become clear that the physicochemical properties of liposomal vaccines - method of antigen attachment, lipid composition, bilayer fluidity, particle charge, and other properties - exert dramatic effects on the resulting immune response. Here, we present a comprehensive review of the physicochemical properties of liposomal vaccines and how they influence immune responses. A discussion of novel and emerging immunomodulators that are suitable for inclusion in liposomal vaccines is also presented. Through a comprehensive analysis of the body of liposomal vaccine literature, we enumerate a series of principles that can guide the rational design of liposomal vaccines to elicit immune responses of a desired magnitude and quality. We also identify major unanswered questions in the field, pointing the direction for future study. PMID- 22306379 TI - New isoform-specific monoclonal antibodies reveal different sub-cellular localisations for talin1 and talin2. AB - Talins are adaptor proteins that connect the integrin family of cell adhesion receptors to cytoskeletal actin. Vertebrates express two closely related talins encoded by separate genes, and while it is well established that talin1 plays a key role in cell adhesion and spreading, little is known about the role of talin2. To facilitate such studies, we report the characterisation of 4 new isoform-specific talin mouse monoclonal antibodies that work in Western blotting, immuno-precipitation, immuno-fluorescence and immuno-histochemistry. Using these antibodies, we show that talin1 and talin2 do not form heterodimers, and that they are differentially localised within the cell. Talin1 was concentrated in peripheral focal adhesions while talin2 was observed in both focal and fibrillar adhesions, and knock-down of talin2 compromised fibronectin fibrillogenesis. Although differentiated human macrophages express both isoforms, only talin1 showed discrete staining and was localised to the ring structure of podosomes. However, siRNA-mediated knock-down of macrophage talin2 led to a significant reduction in podosomal matrix degradation. We have also used the antibodies to localise each isoform in tissue sections using both cryostat and paraffin embedded material. In skeletal muscle talin2 was localised to both myotendinous junctions and costameres while talin1 was restricted to the former structure. In contrast, both isoforms co-localised in kidney with staining of the glomerulus, and the tubular epithelial and interstitial cells of the cortex and medulla. We anticipate that these antibodies will form a valuable resource for future studies on the function of the two major talin isoforms. PMID- 22306380 TI - Suitability of the Montreal cognitive assessment versus the mini-mental state examination in detecting vascular cognitive impairment. AB - The Mini-Mental State Examination (MMSE) has been criticized as being an insufficient screening test for patients with vascular cognitive impairment because of its insensitivity to visuospatial and executive functional deficits. The Montreal Cognitive Assessment (MoCA) was designed to be more sensitive to such deficits, and thus may be a superior screening instrument for vascular cognitive impairment. Twelve patients with extensive leukoaraiosis detected on magnetic resonance imaging (average age, 76.0 +/- 8.7 years) underwent neurologic and cognitive testing, including MMSE and the Japanese version of the MoCA (MoCA J). Accepted cutoff scores of <27 for the MMSE and <26 for the MoCA-J were taken to indicate cognitive impairment. Z-scores were calculated to evaluate the discriminating ability of individual MMSE and MoCA-J subtest scores. Although there was a strong correlation between the total MMSE and total MoCA-J scores (r = 0.90; P < .0001), MMSE scores were skewed toward the higher end of the range (range, 18-30; median, 28), whereas MoCA-J scores were normally distributed (range, 9-28; median, 21). Of the 7 patients with an unimpaired MMSE score, 6 (86%) had an impaired MoCA-J score. Z-scores were >5 for 4 MMSE subtests (orientation, registration, naming, and language) but for only 1 MoCA-J subtest (naming). The MoCA-J better discriminated cognitive status in subjects with extensive leukoaraiosis. Our findings suggest that the MoCA-J is more sensitive than the MMSE in screening for cognitive impairment in patients with subcortical vascular cognitive impairment. PMID- 22306381 TI - Safety of a "drip and ship" intravenous thrombolysis protocol for patients with acute ischemic stroke. AB - BACKGROUND: The "drip and ship" approach for intravenous thrombolysis (IVT) is becoming the standard of care for patients with acute ischemic stroke (AIS) in communities without direct access to a stroke specialist. We aimed to demonstrate the safety of our "drip and ship" IVT protocol. METHODS: This was a retrospective study of patients with AIS treated with IVT between January 2003 and January 2011. Information on patients' baseline characteristics, neuroimaging, symptomatic intracerebral hemorrhage (sICH), and mortality was obtained from our stroke registry. A group of patients were treated with IVT by an emergency physician in phone consultation with a board-certified vascular neurologist (BCVN) at 1 of our 3 stroke network-affiliated hospitals (SNAHs). These patients were subsequently transferred to our Joint Commission-certified primary stroke center (CPSC) after completion of IVT ("drip and ship" protocol). The other patients were treated directly by a BCVN at the CPSC. RESULTS: We studied 201 patients treated with IVT. Of them, 14% received IVT at a SNAH ("drip and ship" protocol) and 86% were treated at the CPSC. There were no significant differences between the 2 groups with regard to age, National Institutes of Health Stoke Scale score, stroke symptom onset-to-needle time, sICH, or in-hospital mortality. CONCLUSIONS: Our "drip and ship" protocol for IVT is safe. The protocol was not associated with an excess of sICH or in-hospital mortality compared with patients who received IVT at the CPSC. PMID- 22306382 TI - Auditing consistency and usefulness of LOINC use among three large institutions - using version spaces for grouping LOINC codes. AB - OBJECTIVES: We wanted to develop a method for evaluating the consistency and usefulness of LOINC code use across different institutions, and to evaluate the degree of interoperability that can be attained when using LOINC codes for laboratory data exchange. Our specific goals were to: (1) Determine if any contradictory knowledge exists in LOINC. (2) Determine how many LOINC codes were used in a truly interoperable fashion between systems. (3) Provide suggestions for improving the semantic interoperability of LOINC. METHODS: We collected Extensional Definitions (EDs) of LOINC usage from three institutions. The version space approach was used to divide LOINC codes into small sets, which made auditing of LOINC use across the institutions feasible. We then compared pairings of LOINC codes from the three institutions for consistency and usefulness. RESULTS: The number of LOINC codes evaluated were 1917, 1267 and 1693 as obtained from ARUP, Intermountain and Regenstrief respectively. There were 2022, 2030, and 2301 version spaces among ARUP and Intermountain, Intermountain and Regenstrief and ARUP and Regenstrief respectively. Using the EDs as the gold standard, there were 104, 109 and 112 pairs containing contradictory knowledge and there were 1165, 765 and 1121 semantically interoperable pairs. The interoperable pairs were classified into three levels: (1) Level I - No loss of meaning, complete information was exchanged by identical codes. (2) Level II - No loss of meaning, but processing of data was needed to make the data completely comparable. (3) Level III - Some loss of meaning. For example, tests with a specific 'method' could be rolled-up with tests that were 'methodless'. CONCLUSIONS: There are variations in the way LOINC is used for data exchange that result in some data not being truly interoperable across different enterprises. To improve its semantic interoperability, we need to detect and correct any contradictory knowledge within LOINC and add computable relationships that can be used for making reliable inferences about the data. The LOINC committee should also provide detailed guidance on best practices for mapping from local codes to LOINC codes and for using LOINC codes in data exchange. PMID- 22306383 TI - ED echo of reverse Tako-tsubo cardiomyopathy: a rare and misleading finding. AB - Tako-tsubo transient cardiomyopathy (TCM) is a syndrome of specific myocardial wall motion abnormalities that appear in response to extreme physiological or emotional stress. The patients have normal coronary arteries and usually present as new-onset heart failure or acute coronary syndrome. We report on a 48-year-old woman with post-community cardiac arrest presenting as an acute myocardial infarction. An emergency physician-performed echocardiogram showed significant wall motion abnormalities, suggesting myocardial infarction. Cardiac catheterization revealed patent epicoronary circulation, and ventriculography demonstrated a rare and only recently described variant of TCM:"reverse" TCM. The patient subsequently died from a subarachnoid hemorrhage. PMID- 22306384 TI - Atropine dosage in patients with severe organophosphate pesticide poisoning. PMID- 22306385 TI - Electrocardiographic manifestations of tramadol toxicity with special reference to their ability for prediction of seizures. AB - AIM: The aims of this study are to determine the electrocardiographic (ECG) manifestations of the symptomatic patients with isolated tramadol toxicity and to predict seizures based on ECG parameters. METHODS: Medical charts of a total of 479 patients with isolated tramadol toxicity were retrospectively evaluated. Their clinical manifestations were recorded, and their ECG parameters including rate, PR interval, QRS duration, corrected QT interval, terminal 40-millisecond frontal plane QRS axis, and the height of R wave and R/S ratio in the lead aVR were measured. The data were analyzed using Kolmogorov-Smirnov test, Mann-Whitney U test, Pearson chi(2), Pearson correlation coefficient (r), and the Student t test. RESULTS: Electrocardiographic heart rate more than 100 beats per minute in 30.6%, QRS 120 milliseconds or more in 7.5%, corrected QT interval more than 440 milliseconds in 24.6%, height of R wave more than 1 mm in lead aVR in 22.1%, R/S ratio more than 0 in lead aVR in 23.5%, terminal 40-millisecond frontal plane QRS axis greater than 120 degrees in 31.7%, and complete or incomplete right bundle branch block in 4.6% of the patients were detected. There were no statistically significant differences between the patients who had not convulsed and those who had convulsed after admission regarding age, sex, vital signs, and ECG findings at presentation (all P values were >.05). CONCLUSIONS: Tramadol toxicity shows ECG changes consistent with sodium channel blockade and potassium channel blockage effects. The risk of development of seizures cannot be predicted based on the changes of ECG parameters at presentation. PMID- 22306386 TI - Hematogenous septic arthritis of the hip in adult patients. PMID- 22306387 TI - ST-segment elevation myocardial infarction in a 37-year-old man with normal coronaries--it is not always cocaine! AB - Heart disease is one of the leading causes of death in the United States. With the increase in substance abuse, the incidence of acute myocardial infarction (MI) in younger population has been on the rise. Traditionally, cocaine has been blamed for acute MI; however, recently, there have been more incidences of marijuana as an inciting factor. We present a case of marijuana-induced acute MI and discuss the proposed mechanism. PMID- 22306388 TI - QT interval--what is normal? Comment on "single-dose ziprasidone associated with QT interval prolongation". PMID- 22306390 TI - Low-velocity knee dislocation in the morbidly obese. AB - Knee dislocations are rare injuries typically associated with severe traumatic mechanisms. We report 2 cases of morbidly obese patients who had complete knee dislocations after falls from standing height. Both cases resulted in significant morbidity secondary to popliteal artery injury. Emergency physicians need to maintain a high index of suspicion for knee dislocations and should be aware of atypical presentations from minor trauma in the obese population. PMID- 22306391 TI - Cervicofacial emphysema and pneumomediastinum after a high-speed air drill endodontic treatment procedure. AB - Cervicofacial subcutaneous emphysema is defined as the abnormal introduction of air in the subcutaneous tissues of the head and neck. It is mainly caused by trauma, head and neck surgery, general anesthesia, and coughing or habitual performance of Valsalva maneuver. The occurrence of subcutaneous emphysema after dental treatment is rare, and diffusion of gas into the mediastinum is much rarer, especially when the procedure is a nonsurgical treatment. The most common dental cause of pneumomediastinum is the introduction of air via the air turbine handpiece during surgical extraction of an impacted tooth. Only 6 cases of pneumomediastinum after endodontic treatment have been reported between 1960 and 2008. Pneumothorax is defined clinically as an "accumulation of air or gas between the parietal and visceral pleurae," and although it is often not a medical emergency, it can result in respiratory distress, tension pneumothorax, shock, circulatory collapse, and even death. Although there are many possible causes of dyspnea during a dental procedure, 1 rare complication is pneumothorax. Although specific closed turbine systems are available for oral surgical procedures, these drills may be used in exodontia to section teeth and facilitate tooth extraction. We report a case of cervical subcutaneous emphysema and pneumomediastinum occurring after an endodontic treatment of right first molar using an air-tribune drill. We present here in a case of massive pneumomediastinum and cervicofacial subcutaneous emphysema that occurred after opening the access cavity for endodontic treatment. We describe its etiologies and guidelines for its prevention during nonsurgical endodontic treatment. PMID- 22306392 TI - Emergency Medical Services and 9-1-1 pandemic influenza preparedness: a national assessment. PMID- 22306393 TI - Another use of the ultrasound-guided transversus abdominis plane block in the ED. PMID- 22306394 TI - Comparing the efficacy of intravenous tenoxicam, lornoxicam, and dexketoprofen trometamol for the treatment of renal colic. AB - STUDY OBJECTIVE: The aim of this study was to compare the efficacy and safety of 3 nonsteroidal anti-inflammatory drugs-intravenous tenoxicam, lornoxicam, and dexketoprofen trometamol-for the treatment of patients with renal colic. METHODS: We conducted a prospective double-blind randomized trial of consecutive adult patients who presented to the emergency department with a chief complaint of acute flank pain and had a clinical diagnosis of suspected acute renal colic. Patients were randomly allocated to receive an intravenous bolus of tenoxicam, lornoxicam, or dexketoprofen trometamol in a blinded fashion. Primary outcome measure of the study was visual analog scale (VAS) score difference at 30 minutes. Secondary outcome measures were VAS scores at 5, 15, and 120 minutes as well as rescue analgesic need at 30 minutes and adverse events during the follow up period. RESULTS: A total of 445 patients were screened, and 123 patients were enrolled in the study. The mean age was 36 +/- 10 years. The mean reduction in VAS pain scores at 30 minutes was 42 +/- 26 mm for tenoxicam, 57 +/- 23 mm for lornoxicam, and 52 +/- 25 mm for dexketoprofen (P = .047). Lornoxicam demonstrated the fastest rate of VAS score reduction over the first 30 minutes. The mean reduction values in VAS pain scores at 5, 15, and 120 minutes were similar among the 3 groups. Rescue analgesics at 30 minutes were required by 16 patients (39%) receiving tenoxicam, 10 patients (24%) receiving lornoxicam, and 8 patients (19%) receiving dexketoprofen (P = .121). No serious adverse events were observed. CONCLUSIONS: Intravenous tenoxicam, lornoxicam, and dexketoprofen are all effective in the treatment of renal colic, although lornoxicam appears to reduce VAS pain scores with the fastest rate in this comparison. PMID- 22306395 TI - Accuracy of emergency physicians using ultrasound measurement of crown-rump length to estimate gestational age in pregnant females. AB - STUDY OBJECTIVE: The objective of this study is to evaluate the accuracy of emergency providers (EPs) of various levels of training in determination of gestational age (GA) in pregnant patients using bedside ultrasound measurement of crown-rump length (CRL). METHODS: We conducted a prospective, cross-sectional, observational study of patients in obstetrical care at an urban county hospital. We enrolled a convenience sample of women at 6 to 14 weeks gestation as estimated by last menstrual period. Emergency providers used ultrasound to measure the CRL. Repeat CRL measurements were performed by either an obstetrical ultrasound technician or senior obstetrician and used as the criterion standard for true GA (TGA). RESULTS: One hundred five patients were evaluated by 20 providers of various levels of training. The average time required to complete the CRL measurement was 85 seconds. When CRL measurements performed by EPs were compared with the TGAs, the average correlation was 0.935 (0.911-0.959). Using standard accepted variance for CRL measurements at different GAs according to the obstetrics literature (+/-3 days for 42-70 days and +/-5 days for 70-90 days), correlation between EP ultrasound and measured TGA was 0.947 (0.927-0.967). CONCLUSIONS: Emergency providers can quickly and accurately determine GA in first trimester pregnancies using bedside ultrasound to calculate the CRL. Emergency providers should consider using ultrasound to calculate the CRL in patients with first-trimester bleeding or pain because this estimated GA may serve as a valuable data point for the future care of that pregnancy. PMID- 22306396 TI - Gastrostomy tube replacement in a pediatric ED: frequency of complications and impact of confirmatory imaging. AB - BACKGROUND: Gastrostomy tube (g-tube) dislodgement is a common problem in special needs children. There are no studies on the frequency of complications after g tube replacement for children in a pediatric emergency department (ED). OBJECTIVES: The objective of this study is to determine the frequency of misplacement and subsequent complications for children undergoing g-tube replacement in a pediatric ED and the impact of contrast-enhanced confirmatory imaging on ED length of stay (LOS). METHODS: This was a retrospective review of children presenting to a pediatric ED over 16 months. Subjects were included if they underwent g-tube replacement in the ED. Records were reviewed for historical and procedural data including patient age, g-tube age, ED LOS, documented difficulties replacing the tube, performance of confirmatory imaging (contrast enhanced radiograph), and complications identified within 72 hours of ED visit. RESULTS: A total of 237 children met inclusion criteria. Three (1.2%) had evidence of g-tube misplacement, all of whom underwent confirmatory imaging. One complication from misplacement was identified (gastric outlet obstruction from overfilled balloon). Tract disruption was not identified for any subject. Eighty four subjects (35%) had confirmatory imaging performed after replacement. Mean ED LOS in the imaged group was 265 vs 142 minutes for the nonimaged group (P < .001). No subjects with documentation of clinical confirmation had subsequent evidence of misplacement. CONCLUSIONS: For children undergoing g-tube replacement in a pediatric ED, misplacement and associated complications were rare. Confirmatory imaging was associated with a considerably longer LOS. In the presence of clinical confirmation, confirmatory imaging may be judiciously used. PMID- 22306397 TI - Acute aortic dissection in the ED: risk factors and predictors for missed diagnosis. AB - OBJECTIVE: This study aims to explore the risk factors and predictors involved in the missed diagnosis of acute aortic dissection (AAD) among patients in the emergency medicine department (EMD). METHODS: This is a single-center retrospective chart review conducted over a 10-year period (January 1998 to December 2008). Records with a diagnosis of "dissection of aorta" (International Classification of Diseases, Ninth Revision code 441.0) from the hospital discharge database and hospital death register were selected. Acute aortic dissection was defined as missed if diagnostic imaging to diagnose AAD or cardiothoracic surgeon consult was not elicited while in the EMD. We compared the history, clinical findings, and investigations between patients who had the diagnosis of AAD missed in the EMD and those who did not. RESULTS: A total of 68 patients were included in the analysis during the study period, of which 38.2% had a missed diagnosis. There was 63.2% of type A AAD by Stanford classification. Neither age, sex, nor a history of hypertension were significant risk factors for missed diagnosis of AAD. The likelihood of missed diagnosis was significantly higher in the absence of a pulse deficit (odds ratio, 35.76; 95% confidence interval, 3.70-345.34) and absence of widened mediastinum on chest radiography (odds ratio, 33.16; 95% confidence interval, 5.74-191.49). CONCLUSION: Well-known risk factors for AAD such as age, male sex, and hypertension were not risk factors for missed diagnosis for AAD presenting in the EMD. The absence of pulse deficit or widened mediastinum does not exclude the diagnosis of AAD. PMID- 22306398 TI - Jejunojejunum intussusception as the single initial manifestation of Henoch Schonlein purpura in a teenager. AB - We described a 14-year-old boy with initial presentation of recurrent intermittent abdominal pain, with subsequent development of jejunojejunum intussusception. The characteristic purpuric skin rash of Henoch-Schonlein purpura appeared later after the surgical manual reduction. When abdominal pain is the single initial manifestation in patients with undiagnosed Henoch-Schonlein purpura, emergency physicians should evaluate if the patient required early surgical intervention such as intussusception or perforation and always keep Henoch-Schonlein purpura as a possibility in mind. PMID- 22306399 TI - Wernicke encephalopathy with atypical magnetic resonance imaging. AB - Wernicke encephalopathy (WE) is a medical emergency caused by thiamine (vitamin B1) deficiency. Typical clinical manifestations are mental change, ataxia, and ocular abnormalities. Wernicke encephalopathy is an important differential diagnosis in all patients with acute mental change. However, the disorder is greatly underdiagnosed. Clinical suspicion, detailed history taking, and neurologic evaluations are important for early diagnosis. Magnetic resonance imaging (MRI) is currently considered the diagnostic method of choice. Typical MRI findings of WE are symmetrical involvement of medial thalamus, mammillary body, and periaqueductal gray matter. Prompt thiamine supplement is important in avoiding unfavorable outcomes. Here, we report a case of alcoholic WE with typical clinical presentation but with atypical MRI. Axial fluid-attenuated inversion recovery images showing symmetrical hyperintensity lesions in dentate nuclei of cerebellum, olivary bodies, and dorsal pons. Although atypical MRI findings are more common in nonalcoholic WE, it can also occur in alcoholic WE. This article is aimed to highlight the potential pitfalls in diagnosing acute mental change, the importance of clinical suspicion, and early treatment in WE. PMID- 22306400 TI - Initial hyperlactatemia in the ED is associated with poor outcome in patients with ischemic stroke. AB - BACKGROUND: Hyperlactatemia may be associated with poor outcome in patients with ischemic stroke because it reflects a state of tissue perfusion. This study aims to know whether initial hyperlactatemia in the emergency department (ED) is associated with poor outcome in patients with ischemic stroke. METHODS: A retrospective observational study was performed in an urban tertiary hospital ED. Patients with an admission diagnosis of ischemic stroke were consecutively enrolled between April 1, 2010, and March 31, 2011. Lactate and glucose levels were obtained at the time of presentation to the ED, whereas the National Institutes of Health Stroke Scale score was assessed at the time of admission. Poor outcome was defined as a modified Rankin scale score greater than or equal to 2 at 3 months. The survival status at 3 months was also obtained. Hyperlactatemia was defined by lactate levels greater than 2 mmol/L. RESULTS: A total of 292 patients were enrolled. At 3 months after stroke, 183 (62.7%) were considered to have poor outcomes, whereas 16 (5.5%) had died. Seventy (24.0%) had initial hyperlactatemia. Multivariable logistic regression analysis showed that hyperlactatemia was independently associated with a higher risk of poor outcome at 3 months (adjusted odd ratio, 2.15; 95% confidence interval, 1.06-4.37; P=.035) and a trend to death at 3 months (adjusted odd ratio, 4.31; 95% confidence interval, 0.91-20.56; P=.066). CONCLUSIONS: Among patients with ischemic stroke, initial hyperlactatemia represents an independent risk factor for poor outcome after controlling for stroke severity, risk factors, initial glucose level, and interval from onset of stroke symptoms to ED arrival. PMID- 22306401 TI - Delayed herniation of intra-abdominal contents after blunt right-sided diaphragm rupture. AB - Right diaphragmatic hernia is a rare injury (0.25%-1%) after blunt abdominal trauma. The diagnosis may be delayed and achieved years after the trauma. We currently report a case of a 48-year-old man who presented to the emergency department at Far Eastern Memorial Hospital, New Taipei City, Taiwan, demonstrating signs of herniation of the right diaphragm. The herniation was confirmed using a chest radiograph. The patient reported falling 3 years before the current evaluation and was symptom-free before arrival in the emergency department. The diagnosis was further confirmed through thoracoabdominal computed tomography. The diaphragmatic hernia was subsequently repaired via abdominal approach. For patients with a history of prior thoracoabdominal trauma with complaints of new abdominal pain, a delayed diaphragmatic hernia should be considered. PMID- 22306402 TI - Alcoholic ketoacidosis coincides with acute Marchiafava-Bignami disease. AB - Alcoholism is the major cause of electrolyte and acid-base imbalance and nutrition deficiency. Ketoacidosis is one of major advised effect on alcoholism. Marchiafava-Bignami disease, a rare alcohol-related disorder, characterized by altered mental status, seizure, and multifocal central nervous system signs, which results from progressive demyelination and necrosis of corpus callosum. Here, we presented a 53-year-old man presented as decreased conscious level and 4 extremity rigidity on admission. Alcoholic ketoacidosis coincided with acute Marchiafava-Bignami disease had been confirmed by biochemistry examination and cranial magnetic resonance imaging. Aggressive hydration with 5% dextrose in normal saline and intravenous vitamin B complex were administered. The patient's symptoms completely recovered after ketoacidosis has been corrected 2 days later. PMID- 22306403 TI - A nexus for gene expression-molecular mechanisms of Spt5 and NusG in the three domains of life. AB - Evolutionary related multisubunit RNA polymerases (RNAPs) transcribe the genomes of all living organisms. Whereas the core subunits of RNAPs are universally conserved in all three domains of life-indicative of a common evolutionary descent-this only applies to one RNAP-associated transcription factor-Spt5, also known as NusG in bacteria. All other factors that aid RNAP during the transcription cycle are specific for the individual domain or only conserved between archaea and eukaryotes. Spt5 and its bacterial homologue NusG regulate gene expression in several ways by (i) modulating transcription processivity and promoter proximal pausing, (ii) coupling transcription and RNA processing or translation, and (iii) recruiting termination factors and thereby silencing laterally transferred DNA and protecting the genome against double-stranded DNA breaks. This review discusses recent discoveries that identify Spt5-like factors as evolutionary conserved nexus for the regulation and coordination of the machineries responsible for information processing in the cell. PMID- 22306405 TI - The structural basis of the kinetic mechanism of a gap-filling X-family DNA polymerase that binds Mg(2+)-dNTP before binding to DNA. AB - DNA with single-nucleotide (1-nt) gaps can arise during various DNA processing events. These lesions are repaired by X-family DNA polymerases (PolXs) with high gap-filling activity. Some PolXs can bind productively to dNTPs in the absence of DNA and fill these 1-nt gaps. Although PolXs have a crucial role in efficient gap filling, currently, little is known of the kinetic and structural details of their productive dNTP binding. Here, we show that Thermus thermophilus HB8 PolX (ttPolX) had strong binding affinity for Mg(2+)-dNTPs in the absence of DNA and that it follows a Theorell-Chance (hit-and-run) mechanism with nucleotide binding first. Comparison of the intermediate crystal structures of ttPolX in a binary complex with dGTP and in a ternary complex with 1-nt gapped DNA and Mg(2+)-ddGTP revealed that the conformation of the incoming nucleotide depended on whether or not DNA was present. Furthermore, the Lys263 residue located between two guanosine conformations was essential to the strong binding affinity of the enzyme. The ability to bind to either syn-dNTP or anti-dNTP and the involvement of a Theorell-Chance mechanism are key aspects of the strong nucleotide-binding and efficient gap-filling activities of ttPolX. PMID- 22306404 TI - Physical chemistry of polyglutamine: intriguing tales of a monotonous sequence. AB - Polyglutamine (polyQ) sequences of unknown normal function are present in a significant number of proteins, and their repeat expansion is associated with a number of genetic neurodegenerative diseases. PolyQ solution structure and properties are important not only because of the normal and abnormal biology associated with these sequences but also because they represent an interesting case of a biologically relevant homopolymer. As the common thread in expanded polyQ repeat diseases, it is important to understand the structure and properties of simple polyQ sequences. At the same time, experience has shown that sequences attached to polyQ, whether in artificial constructs or in disease proteins, can influence structure and properties. The two major contenders for the molecular source of the neurotoxicity implicit in polyQ expansion within disease proteins are a populated toxic conformation in the monomer ensemble and a toxic aggregated species. This review summarizes experimental and computational studies on the solution structure and aggregation properties of both simple and complex polyQ sequences, and their repeat-length dependence. As a representative of complex polyQ proteins, the behavior of huntingtin N-terminal fragments, such as exon-1, receives special attention. PMID- 22306407 TI - Engineering aggregation resistance in IgG by two independent mechanisms: lessons from comparison of Pichia pastoris and mammalian cell expression. AB - Aggregation is an important concern for therapeutic antibodies, since it can lead to reduced bioactivity and increase the risk of immunogenicity. In our analysis of immunoglobulin G (IgG) molecules of identical amino acid sequence but produced either in mammalian cells (HEK293) or in the yeast Pichia pastoris (PP), dramatic differences in their aggregation susceptibilities were encountered. The antibodies produced in Pichia were much more resistant to aggregation under many conditions, a phenomenon found to be mainly caused by two factors. First, the mannose-rich glycan of the IgG from Pichia, while slightly thermally destabilizing the IgG, strongly inhibited its aggregation susceptibility, compared to the complex mammalian glycan. Second, on the Pichia-produced IgGs, amino acids belonging to the alpha-factor pre-pro sequence were left at the N termini of both chains. These additional residues proved to considerably increase the temperature of the onset of aggregation and reduced the aggregate formation after extended incubation at elevated temperatures. The attachment of these residues to IgGs produced in cell culture confirmed their beneficial effect on the aggregation resistance. Secretion of IgGs with native N-termini in the yeast system became possible after systematic engineering of the precursor proteins and the processing site. Taken together, the present results will be useful for the successful production of full-length IgGs in Pichia, give indications on how to engineer aggregation-resistant IgGs and shed new light on potential biophysical effects of tag sequences in general. PMID- 22306406 TI - Identification of a minimal region of the HIV-1 5'-leader required for RNA dimerization, NC binding, and packaging. AB - Assembly of human immunodeficiency virus type 1 (HIV-1) particles is initiated in the cytoplasm by the formation of a ribonucleoprotein complex comprising the dimeric RNA genome and a small number of viral Gag polyproteins. Genomes are recognized by the nucleocapsid (NC) domains of Gag, which interact with packaging elements believed to be located primarily within the 5'-leader (5'-L) of the viral RNA. Recent studies revealed that the native 5'-L exists as an equilibrium of two conformers, one in which dimer-promoting residues and NC binding sites are sequestered and packaging is attenuated, and one in which these sites are exposed and packaging is promoted. To identify the elements within the dimeric 5'-L that are important for packaging, we generated HIV-1 5'-L RNAs containing mutations and deletions designed to eliminate substructures without perturbing the overall structure of the leader and examined effects of the mutations on RNA dimerization, NC binding, and packaging. Our findings identify a 159-residue RNA packaging signal that possesses dimerization and NC binding properties similar to those of the intact 5'-L and contains elements required for efficient RNA packaging. PMID- 22306408 TI - A novel Pim-1 kinase inhibitor targeting residues that bind the substrate peptide. AB - A new screening method using fluorescent correlation spectroscopy was developed to select kinase inhibitors that competitively inhibit the binding of a fluorescently labeled substrate peptide. Using the method, among approximately 700 candidate compounds selected by virtual screening, we identified a novel Pim 1 kinase inhibitor targeting its peptide binding residues. X-ray crystal analysis of the complex structure of Pim-1 with the inhibitor indicated that the inhibitor actually binds to the ATP-binding site and also forms direct interactions with residues (Asp128 and Glu171) that bind the substrate peptide. These interactions, which cause small side-chain movements, seem to affect the binding ability of the fluorescently labeled substrate. The compound inhibited Pim-1 kinase in vitro, with an IC(50) value of 150 nM. Treatment of cultured leukemia cells with the compound reduced the amount of p21 and increased the amount of p27, due to Pim-1 inhibition, and then triggered apoptosis after cell-cycle arrest at the G(1)/S phase. This screening method may be widely applicable for the identification of various new Pim-1 kinase inhibitors targeting the residues that bind the substrate peptide. PMID- 22306409 TI - Theoretical design and screening of panchromatic phthalocyanine sensitizers derived from TT1 for dye-sensitized solar cells. AB - Computational screening of new dyes is becoming an extremely powerful tool, especially when associated with experimental synthetic efforts that might eventually lead to new and more efficient products. Nine novel unsymmetrical zinc phthalocyanine complexes derived from TT1 were designed as sensitizer candidates for dye-sensitized solar cells with three peripheral -CH3, -OH, -OCH3, -OPh, NH2, -NHCH3, -N(CH3)2, -NHPh and -N(Ph)2 substituents as the donors and a carboxyl group as the acceptor. The molecular orbital and the electronic absorption spectra properties of these compounds were studied and compared to those of TT1 using the density functional theory and time-dependent density functional theory calculations at B3LYP level with the LANL2DZ basis set. The novel candidates bearing the -NH2, -NHCH3, -N(CH3)2, -NHPh and -N(Ph)2 moieties as the donors were found to be very promising for providing higher efficiencies than that of TT1 or even the current 4.6% efficiency record held by PcS6. They have higher LUMO levels, smaller energy gaps and red-shifted absorption bands compared to those of TT1. The new absorption bands emerging in 450-600 nm regions may promote ZnPcL-NH2, ZnPcL-NHCH3, ZnPcL-N(CH3)2, ZnPcL-NHPh and ZnPcL-N(Ph)2 from near infrared to panchromatic sensitizers. Further experimental synthetic efforts are in progress in our group to validate the predictions in this report. PMID- 22306410 TI - Probing the simulant behavior of PNPDPP toward parathion and paraoxon: a computational study. AB - The extreme toxicity of organophosphorus nerve agents and pesticides mandates to employ models or simulants in place of the actual compounds in the laboratory. The importance of simulants is known, however, their efficacy for direct comparison with the toxic organophosphorus compounds is not well documented. We have examined the potential energy surfaces (PES) for the alkaline hydrolysis of pesticides like paraoxon (diethyl 4-nitrophenyl phosphate), parathion (O,O diethyl O-4-nitrophenyl phosphorothioate) and PNPDPP (4-nitrophenyl diphenyl phosphate), a simulant with MP2/6-311+G*//B3LYP/6-311+G*+DeltaG(solv) (HF/6 31+G*) level of theory. The effect of aqueous solvation was considered with the Integral Equation Formalism Polarizable Continuum Model (IEF-PCM). The alkaline hydrolysis of these organophosphorus compounds reveals that the reaction proceeds through the attack of hydroxide ion at the phosphorus center to form a pentacoordinate intermediate. The calculated free energies of activation for the alkaline hydrolysis of paraoxon and parathion are in good agreement with the available experimental activation free energies. The computed results show that the reaction profiles for the alkaline hydrolysis of paraoxon, parathion and PNPDPP are largely similar; however, the rate of hydrolysis of parathion may be higher than that of paraxon and PNPDPP. Such difference arises due to the less electrophilic nature of the phosphorus atom of parathion molecule as observed in the charge analysis study. The conceptual DFT analysis also showed the similar trend for the alkaline hydrolysis of paraoxon, parathion and PNPDPP with hydroxide anion. This computational study provides a quantitative support toward the use of PNPDPP as a simulant for organophosphorus compounds, which cannot be used directly for the laboratory purposes. PMID- 22306411 TI - The harmonic analysis of cylindrically symmetric proteins: a comparison of Dronpa and a DNA sliding clamp. AB - The harmonic analysis of two types of proteins with cylindrical symmetry is performed by the Standard Force Field Normal Mode Analysis and by the elastic network model. For both proteins the global elastic modes are assigned to their characteristic topologies. Dronpa is a rigid beta-barrel structure, presenting the twisting, bending and breathing motion of a cylindrical rod. The beta sliding clamp of Escherichia coli is a hexagonal beta-wheel, consisting of rigid segments. In its spectrum four classes of vibrations are identified which are characteristic of an elastic torus. Correlation diagrams and RMSF analysis are compared. The results provide not only a comprehensive validation of the use of both methods to describe the elastic behavior according to the low-frequency normal modes, but also depict the correlated motions of beta-barrel and beta wheel proteins. The harmonic flexibility of the Dronpa protein is compared to the principal components of molecular dynamics (MD) simulation. A functionally important localized cleft opening mode is found, which is not detected by harmonic analysis. PMID- 22306412 TI - Energies and physicochemical properties of cation-pi interactions in biological structures. AB - The cation-pi interactions occur frequently within or between proteins due to six (Phe, Tyr, Trp, Arg, Lys, and His) of the twenty natural amino acids potentially interacting with metallic cations via these interactions. In this study, quantum chemical calculations and molecular orbital (MO) theory are used to study the energies and properties of cation-pi interactions in biological structures. The cation-pi interactions of H+ and Li+ are similar to hydrogen bonds and lithium bonds, respectively, in which the small, naked cations H+ and Li+ are buried deep within the pi-electron density of aromatic molecules, forming stable cation-pi bonds that are much stronger than the cation-pi interactions of other alkali metal cations. The cation-pi interactions of metallic cations with atomic masses greater than that of Li+ arise mainly from the coordinate bond comprising empty valence atomic orbitals (AOs) of metallic cations and pi-MOs of aromatic molecules, though electrostatic interactions may also contribute to the cation-pi interaction. The binding strength of cation-pi interactions is determined by the charge and types of AOs in the metallic cations. Cation-pi interaction energies are distance- and orientation-dependent; energies decrease with the distance (r) and the orientation angle (theta). In solution, the cation-pi energies decrease with the increase of the dielectric constant (E) of the solvent; however, solvation has less influence on the H+-pi and H3O+-pi interactions than on interactions with other cations. The conclusions from this study provide useful theoretical insights into the nature of cation-pi interactions and may contribute to the development of better force field parameters for describing the molecular dynamics of cation-pi interactions within and between proteins. PMID- 22306413 TI - Probing the effect of intermolecular interaction and understanding the electrostatic moments of anacardic acid in the active site of p300 enzyme via DFT and charge density analysis. AB - A charge density analysis has been performed on gas phase and docked forms of anacardic acid molecule to understand its charge density distribution, electrostatic moments and the conformation in the active site of p300 enzyme. Here, we report the binding affinity of anacardic acid with the p300 enzyme calculated from docking analysis. The charge density distribution of anacardic acid molecule in the gas phase as well as the docked form has been determined from the high level quantum chemical calculations using HF and DFT methods coupled with AIM theory. The charge density study on both forms of anacardic acid differentiates its structural and the electrostatic properties in different environments. When the molecule enters into the active site of p300 its conformation, charge density distribution, dipole moment and electrostatic potential are significantly altered in comparison to its gas phase structure. In the active site, the molecule adopts different conformations, its pentadecyl chain is found to be highly twisted; the charges are redistributed and the dipole moment increases from 2.37 to 3.17D. Due to the charge redistribution, the electronegative region of carboxyl group increased as it is found small in the gas phase. The comparisons between both forms reveal the flexibility of anacardic acid in the active site. PMID- 22306414 TI - Molecular modeling study on the possible polymers formed during the electropolymerization of 3-hydroxyphenylacetic acid. AB - The compound 3-hydroxyphenylacetic acid (3-HPA) has been used as a monomer in the synthesis of polymeric films by electropolymerization; these films serve as supports for the immobilization of biomolecules in electrochemical biosensors. To assist in the elucidation of the mechanism of 3-HPA electropolymerization, a systematic quantum mechanical study was conducted. In addition to the monomer, all possible intermediates and the probable oligomers formed during the electropolymerization were investigated using a density functional theory (DFT) method combined with a previous conformational analysis performed with the aid of the RM1 semi-empirical method or a Monte Carlo conformational analysis with the force field OPLS-2005. From the data analysis combined with the experimental results, a mechanism was proposed for the main route of formation of the polymeric films. The mechanism involves the formation of polyethers from the coupling of phenoxide radicals and radicals based on the aromatic ring. PMID- 22306415 TI - Theoretical study on the electronic structure and optical properties of carbazole pi-dimesitylborane as bipolar fluorophores for nondoped blue OLEDs. AB - Molecules with D-pi-A structures are drawing increased attention for applications in organic electronic devices due to their distinct optoelectronic properties. A study of a new series of bipolar fluorophores that have been chemically modified for use as highly efficient nondoped blue organic light-emitting diodes (OLEDs) has been carried out based on existing molecular structures and a literature survey. The aim of this study is to provide a profound interpretation of the optical and electronic properties and the structure-property relationships of a series of new bipolar fluorophores. The study also aims to predict the photophysical and optoelectronic properties of the new fluorophores. The density functional theory (DFT) has been confirmed as reliable, especially in predicting the properties of unknown products. The geometry and the electronic structure of these molecules in the ground state were studied with DFT and ab initio HF, whereas the lowest singlet excited-state geometries were optimized by ab initio singlet configuration interaction (CIS). The absorption and emission spectra, both in the gas phase and in THF, and the lowest singlet excited energies were calculated by employing the time-dependent density functional theory (TDDFT) and the polarizable continuum model (PCM). To precisely predict the charge transporting and charge-confining properties of the new fluorophores, three layered devices have been simulated. The results show that the molecular geometries, HOMOs, LUMOs, energy gaps, ionization potentials (IP), electron affinities (EA), radiative lifetimes (tau), absorption and emission spectra are all tuned by chemical modifications with different pi-conjugated bridges. The results also show that these molecular materials could be used as bipolar light emitting materials for blue and deep-blue OLEDs. PMID- 22306416 TI - Exploring the structure requirement for PKCtheta inhibitory activity of pyridinecarbonitrile derivatives: an in silico analysis. AB - Presently, an in silico modeling was carried out on a large series of 263 PKCtheta inhibitors using 3D-QSAR, molecular docking and molecular dynamics (MD) simulations for the first time. Based on different alignment rules, several computational models were established with their statistical results compared. The resultant models derived from the database alignment exhibit satisfying internal and external predictive capabilities with q2 of 0.503, 0.616 and r2(pred) of 0.568, 0.602 for CoMFA and CoMSIA, respectively. The consistency of conclusion among 3D contour maps of CoMFA and CoMSIA, molecular docking and molecular dynamics proves the reliability of the developed models. The analysis of the 3D contour plots permits interesting conclusions about the effects of different substituent groups at different positions of the common scaffold. In addition, Leu461 and Asn509 have been identified as the key amino acid residues to form H-bond interaction with the ligand compound. The developed models will provide a clue to the design of novel PKCtheta inhibitors. PMID- 22306417 TI - Virtual screening filters for the design of type II p38 MAP kinase inhibitors: a fragment based library generation approach. AB - In this work, we introduce the development and application of a three-step scoring and filtering procedure for the design of type II p38 MAP kinase leads using allosteric fragments extracted from virtual screening hits. The design of the virtual screening filters is based on a thorough evaluation of docking methods, DFG-loop conformation, binding interactions and chemotype specificity of the 138 p38 MAP kinase inhibitors from Protein Data Bank bound to DFG-in and DFG out conformations using Glide, GOLD and CDOCKER. A 40 ns molecular dynamics simulation with the apo, type I with DFG-in and type II with DFG-out forms was carried out to delineate the effects of structural variations on inhibitor binding. The designed docking-score and sub-structure filters were first tested on a dataset of 249 potent p38 MAP kinase inhibitors from seven diverse series and 18,842 kinase inhibitors from PDB, to gauge their capacity to discriminate between kinase and non-kinase inhibitors and likewise to selectively filter-in target-specific inhibitors. The designed filters were then applied in the virtual screening of a database of ten million (107) compounds resulting in the identification of 100 hits. Based on their binding modes, 98 allosteric fragments were extracted from the hits and a fragment library was generated. New type II p38 MAP kinase leads were designed by tailoring the existing type I ATP site binders with allosteric fragments using a common urea linker. Target specific virtual screening filters can thus be easily developed for other kinases based on this strategy to retrieve target selective compounds. PMID- 22306418 TI - The mechanism of copper-catalyzed azide-alkyne cycloaddition reaction: a quantum mechanical investigation. AB - In this study, the mechanism of CuAAC reaction and the structure of copper acetylides have been investigated with quantum mechanical methods, namely B3LYP/6 311+G(d,p). A series of possible copper-acetylide species which contain up to four copper atoms and solvent molecules as ligand has been evaluated and a four copper containing copper-acetylide, M1A, was proposed more likely to form based on its thermodynamic stability. The reaction has been modeled with a representative simple alkyne and a simple azide to concentrate solely on the electronic effects of the mechanism. Later, the devised mechanism has been applied to a real system, namely to the reaction of 2-azido-1,1,1-trifluoroethane and ethynylbenzene in the presence of copper. The copper catalyst transforms the concerted uncatalyzed reaction to a stepwise process and lowers the activation barrier. The pre-reactive complexation of the negatively charged secondary nitrogen of azide and the positively charged copper of copper-acetylide brings the azide and the alkyne to a suitable geometry for cycloaddition to take place. The calculated activation barrier difference between the catalyzed and the uncatalyzed reactions is consistent with faster and the regioselective synthesis of triazole product. PMID- 22306419 TI - Study on the influence of cranberry extract Zuravit S.O.S((r)) on the properties of uropathogenic Escherichia coli strains, their ability to form biofilm and its antioxidant properties. AB - Consumption of cranberries is known to exert positive health effects, especially against urinary tract infections. For this reason, presumably, they are widely used in folk medicine. Different aspects of cranberry phenolics activity were studied in individual papers but complex study in this matter is missing. The aim of the present study is to provide complex data concerning various aspects of cranberry extract activity. We studied the effects of subinhibitory concentrations of commercially available extract (Zuravit S.O.S((r))) against two Escherichia coli strains isolated from urine of patients with pyelonephritis. Additionally the main extract anthocyanins were characterized. The activity of extract against lipid peroxidation and its radical scavenging ability were also assessed. Zuravit S.O.S((r)) decreased the hydrophobicity of one of the studied E. coli strains, reduced swimming motility and adhesion to epithelial cells of both studied strains, it also limited the ability of bacteria to form biofilm. Expression of curli was not affected by cranberry extract, the assessment of P fimbriae expression was not reliable due to extract-induced agglutination of erythrocytes. Cranberry extract caused filamentation in both studied E. coli strains. It also showed pronounced antioxidant and radical scavenging properties. The properties of the studied cranberry extract show that it could be effectively used in prevention and/or elimination of urinary tract infections, specially the recurrent ones. PMID- 22306420 TI - Negative feedback mechanisms surpass the effect of intrinsic EGFR activation during skin chemical carcinogenesis. AB - The negative feedback regulation of epidermal growth factor receptor (EGFR) and other tyrosine kinase receptors, including receptor dephosphorylation and endocytosis followed by degradation, is becoming recognized as a major determinant of receptor function. To evaluate the significance of the negative regulation of EGFR during carcinogenesis in vivo, we subjected the mutant mouse line Dsk5, in which the intrinsic activation of the receptor due to a point mutation is normally counterbalanced by increased posttranslational receptor down regulation, to skin chemical carcinogenesis. Dsk5 mice showed reduced tumor numbers and tumor burden compared with control littermates, and Dsk5-derived tumors showed a reduction in the activation and total levels of EGFR. Furthermore, the transcript levels of several molecules known to act as negative regulators of EGFR were significantly increased in Dsk5-derived tumors. Another intriguing observation was the appearance of tumors with sebaceous differentiation in the ears of Dsk5 mice after chemical carcinogenesis. Further studies are necessary to reveal whether these tumors represent a cell type specific evasion from EGFR negative feedback machinery. In conclusion, this study reveals that several negative feedback regulators contribute to suppression of the intrinsic activation of mutant EGFR during skin carcinogenesis, stressing the potential exploitation of negative regulators as either therapeutic targets or diagnostic tools in cancer and other diseases. PMID- 22306421 TI - Signalling from dead cells drives inflammation and vessel remodelling. AB - Death of vascular smooth muscle cells (VSMCs) has been demonstrated in vessel development and in disease, most notably in atherosclerosis, but also after injury and remodelling. VSMC death promotes multiple features of vulnerable plaques, but also induces features of normal vessel ageing and cystic medial necrosis, including loss of VSMCs, elastin fragmentation and loss, increased glycosaminoglycans and speckled calcification. VSMC apoptosis in the absence of efficient phagocytosis also produces inflammation due to secondary necrosis; in contrast, VSMC apoptosis in normal vessels can be silent. We have investigated the consequences of VSMC apoptosis in both disease and during vessel remodelling. We find that VSMCs release specific cytokines dependent upon the mode of cell death; IL-1beta predominates during apoptosis, whilst IL-1alpha predominates during necrosis. Both IL-1alpha and beta promote release of further cytokines from adjacent live cells, in particular IL-6 and MCP-1. The balance of cytokines results in pathology with differing compositions, including inflammation or neointima formation/vascular repair, via direct promotion of VSMC proliferation and migration. Thus, VSMC death can promote either pathology or repair, depending upon the context and cytokine signalling. PMID- 22306422 TI - Leukoencephalopathy, cerebral calcifications, and cysts: case report. PMID- 22306423 TI - Developmental and maladaptive plasticity in neonatal SCI. AB - Babies and young children with early spinal cord injury (SCI) have evidence of an improved level of recovery over an extended time period. Enhanced neuroplasticity is well recognized in neonatal animal models. In the young human, developmental apraxia and learned early habitual movements mask expression of residual or recovered motor function. Techniques providing sensorimotor stimulation with threshold electrical stimulation (TES) and EMG triggered stimulation (ETS) act to increase awareness and useful function. Small cohort size and prolonged developmental maturation argue for the use of single subject research designs in this population. PMID- 22306424 TI - Unusual manifestations in two cases of necrotizing myopathy associated with SRP antibodies. AB - Anti-SRP (signal recognition particle) positive necrotizing myopathy is commonly not associated with neoplasms. We demonstrate two histologically confirmed cases with unusual manifestations of anti-SRP positive necrotizing myopathy. A 65-year old man presented with rapidly progressing weakness and mild difficulties in swallowing and speaking. Screening for underlying disorders revealed a moderately differentiated renal adenocarcinoma. The muscular symptoms partially improved after tumor nephrectomy and prednisone treatment. However, the patient developed pulmonary metastases and died of the sequelae of pneumonia 11 months after the diagnosis of renal cancer. The second patient developed rapidly complete external ophthalmoplegia, severe bulbar dysarthrophonia and dysphagia, bilateral facial palsy, loss of patellar and ankle jerk reflexes, and severe symmetrical tetraparesis of both proximal and distal muscles. CSF showed mildly increased protein levels, neurography axonal impairment of motor nerves. Screening revealed no evidence for infections, ganglioside antibodies, and carcinoma. MRI was normal. The disease course suggested an overlap syndrome of Miller-Fisher syndrome, axonal Guillain-Barre-syndrome and Bickerstaff brainstem encephalitis. In conclusion SRP antibodies might be found in necrotizing myopathies associated with autoimmune mediated overlap syndromes and neoplasms. The pathomechanism is not clear. Any otherwise unexplained evidence of necrotizing myopathy should prompt the screening for SRP antibodies. PMID- 22306425 TI - Ultrasound-promoted regio and chemoselective synthesis of pyridazinones and phthalazinones catalyzed by ionic liquid [bmim]Br/AlCl3. AB - The first ultrasound-promoted multicomponent synthesis of pyridazinones and phthalazinones from arenes, cyclic anhydrides and ArNHNH(2) in the presence of an efficient recyclable catalyst, [bmim]Br/AlCl(3), in high yield and short reaction time is reported. PMID- 22306426 TI - Drugs of abuse in surface and tap waters of the Tagus River basin: heterogeneous photo-Fenton process is effective in their degradation. AB - This work investigates for the first time the occurrence of drugs of abuse and metabolites in surface waters from the Tagus River on its way through the province of Toledo (downstream Madrid metropolitan area) and in drinking waters in two nearby cities. Some of the studied drugs are used for therapeutic purposes but they can also be consumed as illicit drugs. The results of this preliminary study have revealed the presence of 12 out of 22 drugs of abuse analyzed in fluvial water at concentrations ranging from 1.14 to 40.9 ng/L. The largest concentrations corresponded to the anxiolytics diazepam and lorazepam, the cocaine metabolite benzoilecgonine, the amphetamine-like compound ephedrine, and the methadone metabolite EDDP. All these substances, except for lorazepam, were detected in all the sampling points. Traces of methadone and ephedrine were detected in some samples of tap water. Despite the low concentrations of these pollutants, effects on wildlife or human health cannot be disregarded, especially on vulnerable population. Thus, the treatment of these substances using a heterogeneous photo-Fenton process has been evaluated, rendering a remarkable effectiveness for their degradation. PMID- 22306427 TI - Possible enhancing mechanisms for gene transfer activity of glucuronylglucosyl beta-cyclodextrin/dendrimer conjugate. AB - We previously reported that glucuronylglucosyl-beta-cyclodextrin (GUG-beta-CyD) conjugate with polyamidoamine starburst dendrimer (GUG-beta-CDE conjugate) with the average degree of substitution (DS) of cyclodextrin (CyD) of 1.8 (GUG-beta CDE conjugate (DS 1.8)), showed remarkably higher gene transfer activity than alpha-CyD/dendrimer conjugate (alpha-CDE conjugate (DS 1.2)) and beta CyD/dendrimer conjugate (beta-CDE conjugate (DS 1.3)) in vitro and in vivo. In this study, to clarify the enhancing mechanism for high gene transfer activity of GUG-beta-CDE conjugate (DS 1.8), we investigated the physicochemical properties, cellular uptake, endosomal escape and nuclear translocation of the plasmid DNA (pDNA) complexes as well as pDNA release from the complexes. The particle size, zeta-potential and cellular uptake of GUG-beta-CDE conjugate (DS 1.8)/pDNA complex were mostly comparable to those of alpha-CDE conjugate (DS 1.2) and beta CDE conjugate (DS 1.3). Meanwhile, GUG-beta-CDE conjugate (DS 1.8)/pDNA complex was likely to have high endosomal escaping ability and nuclear localization ability in A549 and RAW264.7 cells. In addition, the pDNA condensation and decondensation abilities of GUG-beta-CDE conjugate (DS 1.8) were lower and higher than that of alpha-CDE conjugate (DS 1.2) or beta-CDE conjugate (DS 1.3), respectively. These results suggest that high gene transfer activity of GUG-beta CDE conjugate (DS 1.8) could be, at least in part, attributed to high endosomal escaping ability, nuclear localization ability and suitable pDNA release from its complex. PMID- 22306428 TI - Safety assessment of nanomaterials: implications for nanomedicine. AB - Nanotechnologies offer exciting opportunities for targeted drug delivery which is anticipated to increase the efficacy of the drug and reduce potential side effects, through the reduction of the dose of the drug in bystander tissues and an increase of the drug at the desired target site. Nevertheless, understanding whether the nano-scale carriers themselves may exert adverse effects is of great importance. The small size may enable nanoparticles to negotiate various biological barriers in the body which could, in turn, give rise to unexpected toxicities. On the other hand, the potential of nanoparticles to cross barriers can also be exploited for drug delivery. Determining the fate of nanoparticles following their therapeutic or diagnostic application is critical: are nanoparticles excreted, or biodegraded, or do they accumulate, potentially leading to harmful long-term effects? The bio-corona of proteins or lipids on the surface of nanoparticles is a key parameter for the understanding of biological interactions of nanoparticles. In the present review, we discuss some of the major challenges related to safety of nanomedicines. PMID- 22306429 TI - Nano- and microparticulate drug carriers for targeting of the inflamed intestinal mucosa. AB - Conventional treatment of inflammatory bowel disease (IBD) is based on the daily administration of high doses of immune-suppressant or anti-inflammatory drugs, often complicated by serious adverse effects. Thus, a carrier system that delivers the drug specifically to the inflamed intestinal regions and shows prolonged drug release would be desirable. The advent of TNF-alpha antibodies and other biopharmaceuticals as potent and specific immune modulators in recent years has broadened the treatment options in IBD, but further increases the necessity for adequate drug delivery, as integrity and bioactivity of the biological active have to be ensured. Exploiting the pathophysiological idiosyncrasies of IBD such as increased mucus production, changes in the structure of the intestinal epithelium and invasion of activated macrophages, different colloidal drug carrier systems have been designed to passively or actively target the site of inflammation. This review introduces different micro- or nanoparticulate drug delivery systems for oral application in IBD therapy for the delivery of small molecular compounds and next generation therapeutics from the group of biological (i.e. peptide and nucleotide based) drugs. PMID- 22306430 TI - Antibody-drug conjugates: basic concepts, examples and future perspectives. AB - Conventional anticancer therapeutics often suffer from lack of specificity, resulting in poor therapeutic indexes and substantial toxicities to normal healthy tissues. Monoclonal antibodies have demonstrated considerable utility in cancer medicine, but their curative potential is often limited. Antibody-drug conjugates represent an innovative therapeutic approach that combines the desirable properties of monoclonal antibodies, with the cell killing activity of cytotoxic drugs, reducing systemic toxicity and increasing the therapeutic benefit for patients. In this review, we outline prominent examples of early and recent antibody-drug conjugates, discussing drugs, linker chemistries and classes of targets for product development. PMID- 22306431 TI - Reply to: Should we, not could we? A commentary on "Pyloric valve transposition as substitute for a colostomy in humans: a preliminary report". PMID- 22306432 TI - Defining a new paradigm for surgical education. PMID- 22306433 TI - Fluorescence competition assay for the assessment of green leaf volatiles and trans-beta-farnesene bound to three odorant-binding proteins in the wheat aphid Sitobion avenae (Fabricius). AB - Odorant-binding proteins (OBPs) are important parts of insect olfactory systems, and sensitive olfaction is vital for phytophagous insects in host foraging. Electrophysiological studies are helpful in understanding olfactory sensing in Sitobion avenae (Hemiptera: Aphididae), but the functions of odorant-binding proteins in this insect are poorly understood. In this study, we used fluorescence competition assays to measure the binding specificities of SaveOBPs. The results showed that both SaveOBP2 and SaveOBP3 were superior to SaveOBP7 in binding green leaf volatiles. It was unexpected that SaveOBP7 bound trans-beta farnesene strongly, which was known as alarm pheromone of this species. Host volatiles were recognized much more easily by SaveOBP2, and the observed binding activity of SaveOBP2 equaled for tested green leaf volatiles. Our results imply that SaveOBP7 might play a more important role in aphid alarm pheromone discrimination. PMID- 22306434 TI - Nurse Education in Practice 2001-2011: an examination of a decade of progress. AB - BACKGROUND: Emerging in 2001, the journal Nurse Education in Practice, according to Crookes (2001: 1), aimed to support "the brave new world of university-based nurse education". As a primarily a practice based journal, this journal aimed to support nurse educators to not only share their research endeavours, but also to share experiences and evidence of good practice. Ten years on it is interesting to analyse the extent to which this journal achieved these aims. AIM: This paper aims to take a look back at patterns and trends, within the journal Nurse Education in Practice, over the past 10 years. METHODS: A triangulation approach was used, whereby all papers (n=466) were subjected to quantitative analysis of trends. Underlying patterns and trends, and inherent meanings were also explored from a qualitative perspective. FINDINGS: Most papers had primarily an educational focus (n=452, 97%), rather than specifically health care (n=14, 3%). The largest majority of papers were classified as case studies. DISCUSSION: Findings reveal that the journal has achieved its goal of supporting nurse educators to share both their research endeavours, and practice experience. Key challenges ahead appear to relate to interprofessional education and clinical roles of educators working in health care. PMID- 22306435 TI - Effects of rapid or slow weight loss on body composition and metabolic risk factors in obese postmenopausal women. A pilot study. AB - To compare the effect of rapid or slow weight loss (WL) on body composition and metabolic risk factors following a caloric restriction. Ten obese, postmenopausal women were matched for total body WL. Dependent variables were: body composition, lipid profile and blood pressure. Both groups decreased obesity measures (all P<=0.05) while lean body mass decreased in the rapid WL group (P<=0.05). Significant improvements in fasting triglyceride level and diastolic blood pressure were observed only in the slow WL group. A slower WL seems to be more beneficial to improve body composition as well as metabolic risk factors in postmenopausal women. PMID- 22306436 TI - Container size influences snack food intake independently of portion size. AB - While larger containers have been found to increase food intake, it is unclear whether this effect is driven by container size, portion size, or their combination, as these variables are usually confounded. The study was advertised as examining the effects of snack food consumption on information processing and participants were served M&M's for free consumption in individual cubicles while watching a TV show. Participants were served (1) a medium portion of M&M's in a small (n=30) or (2) in a large container (n=29), or (3) a large portion in a large container (n=29). The larger container increased intake by 129% (199 kcal) despite holding portion size constant, while controlling for different confounding variables. This research suggests that larger containers stimulate food intake over and above their impact on portion size. PMID- 22306437 TI - Dieting and food craving. A descriptive, quasi-prospective study. AB - Evidence linking food restriction and food craving is equivocal. This study investigated whether dieting was associated with a greater frequency of food craving. Dieting to lose weight was distinguished from watching so as not to gain weight. Participants were 129 women (mean age=41 yrs): 52 were currently dieting to lose weight, 40 were watching their weight, and 37 were non-dieters. They completed a food craving record after every food craving, a food diary, and a daily mood assessment over 7-days. Of the 393 craving incidents recorded, dieters experienced significantly more food cravings than non-dieters, with watchers intermediate. Chocolate was the most craved food (37% of cravings) but neither the types of food, the proportion of cravings leading to eating (~70%), the situations in which cravings occurred, nor the time since the last eating episode differed between groups. Compared with non-dieters, dieters experienced stronger cravings that were more difficult to resist, and for foods they were restricting eating. Watchers showed similarities in experience both to dieters (low hunger) and non-dieters (lower craving intensity). These results support an association between dieting and food craving, the usefulness of distinguishing dieting to lose weight and watching, and suggest a need for further experimental investigation of actual food restriction on food craving experiences. PMID- 22306438 TI - Food choice as a multidimensional experience. A qualitative study with young African American women. AB - As obesity persists in the United States, many public health interventions have been conceived to encourage people to change their diets. These interventions are based on encouraging people to prioritize healthier alternatives in food choice. However a consideration of the existing but limited literature on food choice for diverse populations renders such an assumption problematic. This qualitative study examined the food choices of a population most at risk for obesity - low income African American women - by considering psychological factors, social and cultural meanings of foods, and structural conditions that shape how women decide what to eat. Interviews revealed the complexity of their food choices, illustrating the extent to which multiple influences operate simultaneously on food choice decisions. Implications for obesity prevention are discussed, in particular highlighting the problem that some types of public health interventions do not correspond to the lived experiences of the populations they intend to target. PMID- 22306439 TI - Clinical lung transplantation from uncontrolled non-heart-beating donors revisited. AB - BACKGROUND: The aim of our study is to review and update the long-term results from our previously published series of lung transplantation in uncontrolled non heart-beating donors (NHBDs). METHODS: A prospective collection of data was undertaken from all lung transplants performed among uncontrolled NHBDs between 2002 and December 2009. The statistical analysis was performed using SPSS software and survival was estimated using the Kaplan-Meier method. RESULTS: Twenty-nine lung transplants were performed. Mean total ischemic times for the first and second lung were 575 minutes (SD 115.6) and 701 minutes (SD 111.3), respectively. Primary graft dysfunction (PGD) G1, G2 and G3 occurred in 5 cases (17%), 5 cases (17%) and 11 cases (38%), respectively. Overall hospital mortality rate was 17% (5 patients). Statistical analysis revealed a statistically significant association of mortality with ischemic times and with PGD. In terms of overall survival, 3-month, 1-year, 2-year and 5-year survival rates were 78%, 68%, 57% and 51%, respectively, and the conditional survival rates in those who survived the first 3 months were 86%, 72% and 65%, respectively. The cumulative incidence of bronchiolitis obliterans syndrome (BOS) was 11%, 35% and 45% at 1, 3 and 5 years, respectively. CONCLUSIONS: Lung transplantation from uncontrolled non-heart-beating donors shows acceptable results for both mid- and long-term survival and BOS; however, the higher rates of PGD and its impact on early mortality must make us more demanding with respect to the acceptance criteria and methods of evaluation used with these donors. PMID- 22306440 TI - Hospital charges for pediatric heart transplant hospitalizations in the United States from 1997 to 2006. AB - BACKGROUND: Heart transplantation remains a resource-intensive therapy for children. However, data regarding change in costs over time are scarce. We tested the hypothesis that hospital charges for pediatric heart transplant hospitalizations would increase from 1997 to 2006 and assessed factors associated with hospital charges. METHODS: A retrospective analysis of the Healthcare Cost and Utilization Project Kids' Inpatient Database was performed on admissions surrounding heart transplantation for the years 1997, 2000, 2003, and 2006. The database is a nationwide sampling of pediatric hospital discharges and is weighted to provide national estimates. RESULTS: There were 353 (95% confidence interval, 201-505) pediatric heart transplants in 1997 and 355 (95% confidence interval, 226-485) in 2006. Mean hospital charges increased from $279,399 in 1997 to $451,738 in 2006 (p < 0.001). This increase was similar to that observed for other pediatric surgical diseases. Increases also occurred in morbidities, including pulmonary hypertension (p = 0.04) and sepsis (p = 0.04), and in the use of extracorporeal membrane oxygenation (p = 0.03). On multivariable analysis, greater hospital charges were associated with later calendar year (p = 0.001), stroke (p = 0.03), sepsis (p = 0.001), renal failure (p = 0.008), arrhythmia (p = 0.03), and use of extracorporeal membrane oxygenation (p < 0.001) and ventricular assist device (p < 0.001). CONCLUSIONS: From 1997 to 2006, mean charges for pediatric heart transplant hospitalizations increased by > $170,000 (160%). Although greater morbidities in the later years of the study potentially contributed to increased charges, later calendar year was independently associated with increased charges. The changes in charges for heart transplant are similar to the increases seen in other surgical procedures. Ongoing study of management strategies is needed to determine cost-effective therapies for this complex group of patients. PMID- 22306441 TI - Genotoxicity evaluation of fullerene C60 nanoparticles in a comet assay using lung cells of intratracheally instilled rats. AB - The genotoxicity of fullerene C(60) nanoparticles was evaluated in vivo with comet assays using the lung cells of rats given C(60) nanoparticles. The C(60) nanoparticles were intratracheally instilled as a single dose at 0.5 or 2.5mg/kg or repeated dose at 0.1 or 0.5mg/kg, once a week for 5 weeks, to male rats. The lungs were obtained 3 or 24h after a single instillation and 3h after repeated instillation. Inflammatory responses were observed in the lungs obtained 24h after a single instillation at 2.5mg/kg and repeated instillation at 0.5mg/kg. Histopathological examinations revealed that C(60) nanoparticles caused slight changes including hemorrhages in alveoli and the cellular infiltration of macrophages and neutrophils in alveoli. In comet assays using rat lung cells, no increase in % Tail DNA was found in any group given C(60) nanoparticles. These findings indicate that C(60) nanoparticles had no potential for DNA damage in comet assays using the lungs cells of rats given C(60) even at doses causing inflammation. PMID- 22306442 TI - Efficacy, efficiency and safety aspects of hydrogen peroxide vapour and aerosolized hydrogen peroxide room disinfection systems. AB - BACKGROUND: This was a head-to-head comparison of two hydrogen-peroxide-based room decontamination systems. AIM: To compare the efficacy, efficiency and safety of hydrogen peroxide vapour (HPV; Clarus R, Bioquell, Andover, U.K.) and aerosolized hydrogen peroxide (aHP; SR2, Sterinis, now supplied as Glosair, Advanced Sterilization Products (ASP), Johnson & Johnson Medical Ltd, Wokingham, U.K.) room disinfection systems. METHOD: Efficacy was tested using 4- and 6-log Geobacillus stearothermophilus biological indicators (BIs) and in-house prepared test discs containing approximately 10(6) meticillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile and Acinetobacter baumannii. Safety was assessed by detecting leakage of hydrogen peroxide using a hand-held detector. Efficiency was assessed by measuring the level of hydrogen peroxide using a hand held sensor at three locations inside the room, 2 h after the start of the cycles. FINDINGS: HPV generally achieved a 6-log reduction, whereas aHP generally achieved less than a 4-log reduction on the BIs and in-house prepared test discs. Uneven distribution was evident for the aHP system but not the HPV system. Hydrogen peroxide leakage during aHP cycles with the door unsealed, as per the manufacturer's operating manual, exceeded the short-term exposure limit (2 ppm) for more than 2 h. When the door was sealed with tape, as per the HPV system, hydrogen peroxide leakage was <1 ppm for both systems. The mean concentration of hydrogen peroxide in the room 2 h after the cycle started was 1.3 [standard deviation (SD) 0.4] ppm and 2.8 (SD 0.8) ppm for the four HPV and aHP cycles, respectively. None of the readings were <2 ppm for the aHP cycles. CONCLUSION: The HPV system was safer, faster and more effective for biological inactivation. PMID- 22306443 TI - Assessment of administrative data for evaluating the shifting acquisition of Clostridium difficile infection in England. AB - BACKGROUND: Little is known about the acquisition of Clostridium difficile infection (CDI) and whether it represents hospital- or community-acquired infection. AIM: To test the feasibility and value of using national hospital admissions data from Hospital Episode Statistics to examine trends in CDI in England. METHODS: Hospital Episode Statistics from the period 1997/98 to 2009/10 were used. Time trends were analysed using two different denominators of hospital activity: total admissions and total bed-days. We explored the impact of sociodemographic factors, comorbidity and healthcare pathways on the risk of CDI. FINDINGS: CDI rates per admission and per bed-days increased from 1997/98 to 2006/07, then decreased significantly by >50% from 2008/9 and 2009/10. This pattern was similar for patients regardless of probable source of infection but the proportion of probable community-acquired CDI cases rose steadily from 7% in 1997/98 to 13% in 2009/10. CDI rates were higher among older patients (odds ratio: >65 years, 10.9), those with more comorbid conditions (odds ratio for Charlson index: >5, 5.6), and among patients admitted as an emergency compared with elective admissions, but no relationship was found with deprivation score. CONCLUSION: Our findings support not only the falling trend in CDI found in the national mandatory surveillance scheme from the Health Protection Agency, but a growing proportion of CDI presenting on admission with no evidence of prior hospital exposure in the previous 90 days. We suggest that these may be community acquired CDI cases. PMID- 22306444 TI - Evaluation of laser-speckle contrast image analysis techniques in the cortical microcirculation of piglets. AB - A new laser speckle-contrast analysis (LASCA) technique based on multi-exposure imaging was employed to simultaneously study pial arteriolar responses with cerebrocortical perfusion changes to various vasodilator (5-10% CO(2) ventilation, bradykinin (1-10 MUM), N-methyl-D-aspartate (100 MUM)) vasoconstrictor (10-100 MUM noradrenaline, 1M KCl), or neutral (2.1% H(2) ventilation) stimuli as well as to asphyxia in the newborn piglet. Anesthetized, ventilated animals (n=20) were fitted with closed cranial windows. Multiple exposure laser-speckle image series (1-100 ms) were obtained using a near infrared diode laser (lambda=808 nm). The autocorrelation decay time (tau) of speckle fluctuations was determined over pial arterioles and parenchymal areas to express 1/tau being proportional to blood flow velocity by two different LASCA techniques: our novel multi-exposure or a single exposure (2 and 20 ms) approach. 1/tau values yielded by different LASCA techniques were not significantly different at most points. LASCA easily detected both increases and decreases in cortical blood flow (CoBF). Cortical 1/tau changes to hypercapnia closely matched quantitative CoBF data determined previously, and were also in accordance with increases of pial arteriolar blood flow, calculated from arteriolar flow velocity and cross sectional area changes. In summary, LASCA emerges as an appealing method to simultaneously study microvascular reactivity and cortical perfusion changes in the piglet. PMID- 22306445 TI - Ion beam induced amorphization and bond breaking in Zn2SiO4:Eu3+ nanocrystalline phosphor. AB - This paper reports on the ionoluminescence (IL) of Zn(2)SiO(4):Eu(3+) nanophosphors bombarded with 100 MeV Si(7+) ions with fluences in the range (3.91 21.48)*10(12) ions cm(-2). The prominent IL emission peaks recorded at 580, 590, 612, 650 and 705 nm are attributed to the luminescence centers activated by Eu(3+) ions. It is observed that IL intensity decreases and saturates with increase of Si(7+) ion fluence. Fourier transform infrared (FT-IR) studies confirm surface/bulk amorphization for a fluence of (3.91-21.48)*10(13) ions cm( 2). These results show degradation of SiO (2nu(3)) bonds present on the surface of the sample and/or due to lattice disorder produced by dense electronic excitation under heavy ion irradiation. These results are discussed in detail. PMID- 22306446 TI - Cadmium telluride nanoparticles loaded on activated carbon as adsorbent for removal of sunset yellow. AB - Adsorption is a promising technique for decolorization of effluents of textile dyeing industries but its application is limited due to requirement of high amounts of adsorbent required. The objective of this study was to assess the potential of cadmium telluride nanoparticles loaded onto activated carbon (CdTN AC) for the removal of sunset yellow (SY) dye from aqueous solution. Adsorption studies were conducted in a batch mode varying solution pH, contact time, initial dye concentration, CdTN-AC dose, and temperature. In order to investigate the efficiency of SY adsorption on CdTN-AC, pseudo-first-order, pseudo-second-order, Elovich, and intra-particle diffusion kinetic models were studied. It was observed that the pseudo-second-order kinetic model fits better than other kinetic models with good correlation coefficient. Equilibrium data were fitted to the Langmuir model. Thermodynamic parameters such as enthalpy, entropy, activation energy, and sticking probability were also calculated. It was found that the sorption of SY onto CdTN-AC was spontaneous and endothermic in nature. The proposed adsorbent is applicable for SY removal from waste of real effluents including pea-shooter, orange drink and jelly banana with efficiency more than 97%. PMID- 22306447 TI - Theoretical and experimental studies on the vibrational spectra of 3 quinolinecarboxaldehyde. AB - Combined experimental and theoretical studies have been performed on the structure and vibrational spectra (IR and Raman spectra including far region) of 3-quinolinecarboxaldehyde. Hartree-Fock (HF) and density functional theory (DFT) B3LYP calculations have been employed with the 6-311++G(d,p) basis set for investigating the structural and spectroscopic properties of the Rot 1 and Rot 2 conformers of 3-quinolinecarboxaldehyde. The B3LYP frequencies are closer to the experimental frequencies than the HF frequencies, but scaled frequencies of both HF and B3LYP agree almost perfectly with the experimental frequencies. The Rot 1 conformer has been found more stable than the Rot 2 conformer. The scaled vibrational frequencies of Rot 1 conformer also agree slightly better than those of the Rot 2 conformer compared with the experimental frequencies. These indicate that 3-quinolinecarboxaldehyde has Rot 1 conformation in its ground state. PMID- 22306448 TI - Highly selective and sensitive colorimetric probe for hydrogen sulfide by a copper (II) complex of azo-dye based on chemosensing ensemble approach. AB - A copper (II) complex of azo-dye (Cu-1) has been synthesized by the reaction of 1 (2-pyridylazo)-2-naphthol (1) with copper (II) chloride. The complex Cu-1 is able to selectively sense hydrogen sulfide over other anions followed by the release of compound 1 to give a remarkable change of UV-vis absorption at neutral pH in aqueous solution. PMID- 22306449 TI - A novel coumarin Schiff-base as a Ni(II) ion colorimetric sensor. AB - A novel coumarin Schiff base compound (L) prepared from 7-diethylaminocoumarin-3 aldehyde and 3-amino-7-hydroxycoumarin was synthesized and evaluated as a chemoselective Ni(2+) sensor. Addition of Ni(2+) to CH(3)CN solution of L resulted in a rapid color change from yellow to red together with a large red shift from 465 to 516 nm. Moreover, other common alkali-, alkaline earth-, transition- and rare earth metal ions induced no or minimal spectral changes. Experimental results indicated that L could be used as a potential Ni(2+) colorimetric and naked-eye chemosensor in CH(3)CN solution. PMID- 22306450 TI - Investigation of the inclusion complex of beta-cyclodextrin with mycophenolate mofetil. AB - The acid-base equilibrium of mycophenolate mofetil is studied in the absence and presence of beta-cyclodextrin (beta-CD). The conditional acidity constants are obtained by rank annihilation factor analysis (RAFA) as a function of beta-CD concentrations. Also the stability constants for inclusion complexes of beta-CD with both acidic and basic forms are calculated. The conditional acidity constant decreases by increasing beta-CD concentration. The calculated stability constants show that the acidic form of mycophenolate mofetil forms more stable inclusion complex (552+/-7 M(-1)) than its basic anionic form (158+/-2 M(-1)). PMID- 22306451 TI - Spectroscopic study on the interaction of ct-DNA with manganese Salen complex containing triphenyl phosphonium groups. AB - The DNA binding properties of a bulky and hydrophobic Schiff base complex of manganese(III) [N,N'-bis(5-(triphenyl phosphonium methyl)salicylidene)-1,2 ethylene diamine chloride Mn(III) acetate] was examined by spectroscopic techniques. UV-vis titration data indicate both hypo and hyperchromic effect with addition of DNA to complex. A competitive binding study showed that the enhanced emission intensity of ethidium bromide (EB) in the presence of DNA was quenched by adding Mn Salen complex. This finding indicates that Mn Salen complex displaces EB from its binding site in DNA. Helix melting studies indicate improvement in the helix stability, and an increase in the melting temperature. The analysis of CD spectra represents the structural changes in DNA due to the binding of Mn Salen complex. The binding constant has been calculated using absorbance and fluorescence data. The results also represent that the binding process proceeds by strong electrostatic and hydrophobic interactions. PMID- 22306452 TI - Neural network consistent empirical physical formula construction for density functional theory based nonlinear vibrational absorbance and intensity of 6 choloronicotinic acid molecule. AB - Being directly related to the electric charge distributions in a molecule, the vibrational spectra intensities are both experimentally and theoretically important physical quantities. However, these intensities are inherently highly nonlinear and of complex pattern. Therefore, in particular for unknown detailed spatial molecular structures, it is difficult to make ab initio intensity calculations to compare with new experimental data. In this respect, we very recently initiated entirely novel layered feedforward neural network (LFNN) approach to construct empirical physical formulas (EPFs) for density functional theory (DFT) vibrational spectra of some molecules. In this paper, as a new and far improved contribution to our novel molecular vibrational spectra LFNN-EPF approach, we constructed LFFN-EPFs for absorbances and intensities of 6 choloronicotinic acid (6-CNA) molecule. The 6-CNA data, borrowed from our previous study, was entirely different and much larger than the vibrational intensity data of our formerly used LFNN-EPF molecules. In line with our another previous work which theoretically proved the LFNN relevance to EPFs, although the 6-CNA DFT absorbance and intensity were inherently highly nonlinear and sharply fluctuating in character, still the optimally constructed train set LFFN-EPFs very successfully fitted the absorbances and intensities. Moreover, test set (i.e. yet-to-be measured experimental data) LFNN-EPFs consistently and successfully predicted the absorbance and intensity data. This simply means that the physical law embedded in the 6-CNA vibrational data was successfully extracted by the LFNN-EPFs. In conclusion, these vibrational LFNN-EPFs are of explicit form. Therefore, by various suitable operations of mathematical analysis, they can be used to estimate the electronic charge distributions of the unknown molecule of the significant complexity. Additionally, these estimations can be combined with those of theoretical DFT atomic polar tensor calculations to contribute to the identification of the molecule. PMID- 22306453 TI - Chronic stress enhances progression of acute lymphoblastic leukemia via beta adrenergic signaling. AB - Clinical studies suggest that stress-related biobehavioral factors can accelerate the progression of hematopoietic cancers such as acute lymphoblastic leukemia (ALL), but it is unclear whether such effects are causal or what biological pathways mediate such effects. Given the network of sympathetic nervous system (SNS) fibers that innervates the bone marrow to regulate normal (non-leukemic) hematopoietic progenitor cells, we tested the possibility that stress-induced SNS signaling might also affect ALL progression. In an orthotopic mouse model, Nalm-6 human pre-B ALL cells were transduced with the luciferase gene for longitudinal bioluminescent imaging and injected i.v. into male SCID mice for bone marrow engraftment. Two weeks of daily restraint stress significantly enhanced ALL tumor burden and dissemination in comparison to controls, and this effect was blocked by the beta-adrenergic antagonist, propranolol. Although Nalm-6 ALL cells expressed mRNA for beta1- and beta3-adrenergic receptors, they showed no evidence of cAMP signaling in response to norepinephrine, and norepinephrine failed to enhance Nalm-6 proliferation in vitro. These results show that chronic stress can accelerate the progression of human pre-B ALL tumor load via a beta-adrenergic signaling pathway that likely involves indirect regulation of ALL biology via alterations in the function of other host cell types such as immune cells or the bone marrow microenvironment. PMID- 22306454 TI - Psychological stress is associated with high levels of IL-6 in HIV-1 infected individuals on effective combined antiretroviral treatment. AB - This study explores the role of psychological stress in the circulating levels of interleukin-6 (IL-6) in a group of HIV-1 infected individuals on effective cART. We developed a cross-sectional study with 50 individuals with confirmed diagnosis of HIV-1 infection >=1 and <=8 years, on continuous cART for >1 and <8 years and with plasma viral load <50 copies/mL for at least 1 year. Clinical, behavioral and psychological variables were collected to control their possible indirect contribution in the relationship between psychological stress and IL-6. Pearson correlation and univariate/multivariate logistic regressions were performed. Eighty-eight percent of the subjects were male: median (IQR) age: 39.0 (32.7 42.2), years since HIV-1 infection: 3.4 (2.1-7.0), years on cART: 2.5 (1.6-5.7), CD4 cell count: 709.0 (573.5-881.0) cell/mm(3), plasma levels of IL-6: 7.0 (0 12.2) pg/ml. A strong correlation between IL-6 and psychological stress was found (r=.81). Psychological stress (coef: 0.49; SD: 0.05), anxiety/depression (0.37; 0.08) and unhealthy diet (2.94; 1.38) were associated with higher levels of IL-6. In the multivariate model psychological stress remained strongly associated with IL-6 (R(2): 59%). In conclusion, individuals with psychological stress presented high levels of IL-6 and psychological stress was the only variable which remained strongly associated with IL-6. This strong relationship suggests evidence for a mechanism through which psychological stress might contribute to the health's impairment of HIV-infected individuals on effective cART. PMID- 22306455 TI - Immunological parameters in elderly women: correlations with aerobic power, muscle strength and mood state. AB - PURPOSE: Our objective was to relate immunological data for healthy but sedentary elderly women to aerobic power, strength, and mood state. METHODS: We measured peak aerobic power and one-repetition maximum strength along with mood (depression and fatigue), quality of life and carbohydrate intake on 42 women aged 60-77 years. Standard immunological techniques determined natural killer cell count and cytotoxic activity (NKCA), proliferative responses to phytohemaglutinin and OKT(3), various lymphocyte subpopulations (CD3(+), CD3( )CD19(+), CD56(+), CD4(+), CD8(+), CD56(dim) and CD56(bright)), and markers of activation, maturation, down-regulation and susceptibility to apoptosis (CD25(+), CD28(+), CD45RA(+), CD45RO(+), CD69(+), CD95(+), HLA-DR(+)). RESULTS: Correlations of immune parameters with aerobic power and strength were very similar for absolute and relative immunological data. In the group as a whole, the only correlation with aerobic power was -0.35 (relative CD4(+)CD69(+) count), but in subjects with values <22.6 mL kg(-1)min(-1) correlations ranged from -0.57 (relative CD4(+)CD45RO(+)) to 0.92 (absolute CD56(dim)HLA-DR(+)). In terms of muscle strength, univariate correlation coefficients ranged from -0.34 (relative and absolute CD3(+)CD4(+)CD8(+)) to +0.48 (absolute CD3(+)HLA-DR(+)) and +0.50 (absolute CD8(+)CD45RA(+)CD45RO(+)). Neither NKCA nor lymphocyte proliferation were correlated with aerobic power or muscle strength. Although mood state and quality of life can sometimes be influenced by an individual's fitness level, our multivariate analyses suggested that depression, fatigue and quality of life were more important determinants of immune profile than our fitness measures. CONCLUSIONS: Psychological changes associated with aging may have a substantial adverse effect upon the immune system, and immunological function may be enhanced more by addressing these issues than by focusing upon aerobic or resistance training. PMID- 22306456 TI - Minimum data elements for research reports on CFS. AB - Chronic fatigue syndrome (CFS) is a debilitating condition that has received increasing attention from researchers in the past decade. However, it has become difficult to compare data collected in different laboratories due to the variability in basic information regarding descriptions of sampling methods, patient characteristics, and clinical assessments. The issue of variability in CFS research was recently highlighted at the NIH's 2011 State of the Knowledge of CFS meeting prompting researchers to consider the critical information that should be included in CFS research reports. To address this problem, we present our consensus on the minimum data elements that should be included in all CFS research reports, along with additional elements that are currently being evaluated in specific research studies that show promise as important patient descriptors for subgrouping of CFS. These recommendations are intended to improve the consistency of reported methods and the interpretability of reported results. Adherence to minimum standards and increased reporting consistency will allow for better comparisons among published CFS articles, provide guidance for future research and foster the generation of knowledge that can directly benefit the patient. PMID- 22306457 TI - Towards non-reductionistic medical anthropology, medical education and practitioner-patient-interaction: the example of Anthroposophic Medicine. AB - OBJECTIVE: To develop the hypothesis that reductionism in medical anthropology, professional education and health care influences empathy development, communication and patient satisfaction. METHOD: We identified relevant literature and reviewed the material in a structured essay. We reflected our hypothesis by applying it to Anthroposophic Medicine (AM), an example of holistic theory and practice. RESULTS: Reductionism in medical anthropology such as in conventional medicine seems to lead to a less empathetic and less communicative health care culture than holism such as in CAM disciplines. However, reductionism can be transformed into a systemic, multi-perspective holistic view, when the emergent properties of the physical, living, psychic, spiritual and social levels of human existence and the causal relations between them are more carefully accounted for in epistemology, medical anthropology and professional education. This is shown by the example of AM and its possible benefits for communication with and satisfaction of patients. CONCLUSION: A non-reductionistic understanding of the human being may improve communication with patients and enhance patient benefit and satisfaction. PRACTICE IMPLICATIONS: Interdisciplinary qualitative and quantitative studies are warranted to test this hypothesis and to understand the complex relations between epistemology, medical anthropology, education, health care delivery and benefit for patients. PMID- 22306458 TI - The health professional-patient-relationship in conventional versus complementary and alternative medicine. A qualitative study comparing the perceived use of medical shared decision-making between two different approaches of medicine. AB - OBJECTIVE: To explore differences between conventional medicine (COM) and complementary and alternative medicine (CAM) regarding the attitude toward and the perceived use of shared decision-making (SDM) from the health professional perspective. METHODS: Thirty guideline-based interviews with German GPs and nonmedical practitioners were conducted using qualitative analysis for interpretation. RESULTS: The health professional-patient-relationship in CAM differs from that in COM, as SDM is perceived more often. Reasons for this include external context variables (e.g., longer consultation time) and internal provider beliefs (e.g., attitude toward SDM). German health care policy was regarded as one of the most critical factors which affected the relationship between GPs and their patients and their practice of SDM. CONCLUSION: Differences between COM and CAM regarding the attitude toward and the perceived use of SDM are attributable to diverse concepts of medicine, practice context variables and internal provider factors. Therefore, the perceived feasibility of SDM depends on the complexity of different occupational socialization processes and thus, different value systems between COM and CAM. PRACTICE IMPLICATIONS: Implementation barriers such as insufficient communication skills, lacking SDM training or obedient patients should be reduced. Especially in COM, contextual variables such as political restrictions need to be eliminated to successfully implement SDM. PMID- 22306459 TI - Essential tremor is not dependent upon cerebellar Purkinje cell loss. AB - The pathophysiology of essential tremor (ET) is unknown but recent studies report that the majority of ET cases has cerebellar Purkinje cell (PC) degeneration and its sequelae. OBJECTIVE: To perform PC counts in ET, and normal and Parkinson's disease (PD) controls to determine the relationship of PC loss to ET. METHODS: All ET cases and PD controls were followed at our clinic. Normal controls had no history of neurological disease and had normal standard neuropathological studies. The PC counts were done by a neuropathologist who was blinded to the clinical diagnosis. Three different methods were used for counting PC; section through any part of the PC, through any part of the PC nucleus, and through any part of PC nucleolus. The counts were done in five non-contiguous microscopic fields. RESULTS: 59 brains were studied. These included 12 ET, 41 PD controls, and six normal controls. The mean age at death was 82.7 in ET, 79.1 in PD, and 75.7 years in the normal controls. The mean duration of symptoms was 34 years in ET and 15.7 years in the PD cases. The mean PC counts through any part of the neuron were 64.8 in ET, 56.2 in PD, and 58.0 in normal controls. Differences were not significant. CONCLUSION: Cerebellar PC loss does not distinguish ET from controls. It is concluded that PC loss is neither a pathological basis for, nor the distinctive feature of ET. PMID- 22306460 TI - Small-angle X-ray scattering and single-molecule FRET spectroscopy produce highly divergent views of the low-denaturant unfolded state. AB - The results of more than a dozen single-molecule Forster resonance energy transfer (smFRET) experiments suggest that chemically unfolded polypeptides invariably collapse from an expanded random coil to more compact dimensions as the denaturant concentration is reduced. In sharp contrast, small-angle X-ray scattering (SAXS) studies suggest that, at least for single-domain proteins at non-zero denaturant concentrations, such compaction may be rare. Here, we explore this discrepancy by studying protein L, a protein previously studied by SAXS (at 5 degrees C), which suggested fixed unfolded-state dimensions from 1.4 to 5 M guanidine hydrochloride (GuHCl), and by smFRET (at 25 degrees C), which suggested that, in contrast, the chain contracts by 15-30% over this same denaturant range. Repeating the earlier SAXS study under the same conditions employed in the smFRET studies, we observe little, if any, evidence that the unfolded state of protein L contracts as the concentration of GuHCl is reduced. For example, scattering profiles (and thus the shape and dimensions) collected within ~4 ms after dilution to as low as 0.67 M GuHCl are effectively indistinguishable from those observed at equilibrium at higher denaturant. Our results thus argue that the disagreement between SAXS and smFRET is statistically significant and that the experimental evidence in favor of obligate polypeptide collapse at low denaturant cannot be considered conclusive yet. PMID- 22306461 TI - Cryo-EM structure of the archaeal 50S ribosomal subunit in complex with initiation factor 6 and implications for ribosome evolution. AB - Translation of mRNA into proteins by the ribosome is universally conserved in all cellular life. The composition and complexity of the translation machinery differ markedly between the three domains of life. Organisms from the domain Archaea show an intermediate level of complexity, sharing several additional components of the translation machinery with eukaryotes that are absent in bacteria. One of these translation factors is initiation factor 6 (IF6), which associates with the large ribosomal subunit. We have reconstructed the 50S ribosomal subunit from the archaeon Methanothermobacter thermautotrophicus in complex with archaeal IF6 at 6.6 A resolution using cryo-electron microscopy (EM). The structure provides detailed architectural insights into the 50S ribosomal subunit from a methanogenic archaeon through identification of the rRNA expansion segments and ribosomal proteins that are shared between this archaeal ribosome and eukaryotic ribosomes but are mostly absent in bacteria and in some archaeal lineages. Furthermore, the structure reveals that, in spite of highly divergent evolutionary trajectories of the ribosomal particle and the acquisition of novel functions of IF6 in eukaryotes, the molecular binding of IF6 on the ribosome is conserved between eukaryotes and archaea. The structure also provides a snapshot of the reductive evolution of the archaeal ribosome and offers new insights into the evolution of the translation system in archaea. PMID- 22306462 TI - Time-dependent predominance of nonhomologous DNA end-joining pathways during embryonic development in mice. AB - Repair of DNA double-strand breaks (DSBs) is crucial for maintaining genomic integrity during the successful development of a fertilized egg into a whole organism. To date, the mechanism of DSB repair in postimplantation embryos has been largely unknown. In the present study, using a cell-free repair system derived from the different embryonic stages of mice, we find that canonical nonhomologous end joining (NHEJ), one of the major DSB repair pathways in mammals, is predominant at 14.5 day of embryonic development. Interestingly, all four types of DSBs tested were repaired by ligase IV/XRCC4 and Ku-dependent classical NHEJ. Characterization of end-joined junctions and expression studies further showed evidences for canonical NHEJ. Strikingly, in contrast to the above, we observed noncanonical end joining accompanied by DSB resection, dependent on microhomology and ligase III in 18.5-day embryos. Interestingly, we observed an elevated expression of CtIP, MRE11, and NBS1 at this stage, suggesting that it could act as a switch between classical end joining and microhomology-mediated end joining at later stages of embryonic development. Thus, our results establish for the first time the existence of both canonical and alternative NHEJ pathways during the postimplantation stages of mammalian embryonic development. PMID- 22306463 TI - A structural model for the generation of continuous curvature on the surface of a retroviral capsid. AB - The genome of a retrovirus is surrounded by a convex protein shell, or capsid, that helps facilitate infection. The major part of the capsid surface is formed by interlocking capsid protein (CA) hexamers. We report electron and X-ray crystallographic analysis of a variety of specimens assembled in vitro from Rous sarcoma virus (RSV) CA. These specimens all contain CA hexamers arranged in planar layers, modeling the authentic capsid surface. The specimens differ only in the number of layers incorporated and in the disposition of each layer with respect to its neighbor. The body of each hexamer, formed by the N-terminal domain of CA, is connected to neighboring hexamers through C-terminal domain dimerization. The resulting layer structure is very malleable due to inter-domain flexibility. A helix-capping hydrogen bond between the two domains of RSV CA creates a pivot point, which is central to controlling their relative movement. A similar mechanism for the governance of inter-domain motion was recently described for the human immunodeficiency virus type 1 (HIV-1) capsid, although there is negligible sequence identity between RSV and HIV-1 CA in the region of contact, and the amino acids involved in creating the pivot are not conserved. Our observations allow development of a physically realistic model for the way neighboring hexamers can tilt out of plane, deforming the hexamer layer and generating the continuously curved surfaces that are a feature of all retroviral capsids. PMID- 22306464 TI - Isolation of an asymmetric RNA uncoating intermediate for a single-stranded RNA plant virus. AB - We have determined the three-dimensional structures of both native and expanded forms of turnip crinkle virus (TCV), using cryo-electron microscopy, which allows direct visualization of the encapsidated single-stranded RNA and coat protein (CP) N-terminal regions not seen in the high-resolution X-ray structure of the virion. The expanded form, which is a putative disassembly intermediate during infection, arises from a separation of the capsid-forming domains of the CP subunits. Capsid expansion leads to the formation of pores that could allow exit of the viral RNA. A subset of the CP N-terminal regions becomes proteolytically accessible in the expanded form, although the RNA remains inaccessible to nuclease. Sedimentation velocity assays suggest that the expanded state is metastable and that expansion is not fully reversible. Proteolytically cleaved CP subunits dissociate from the capsid, presumably leading to increased electrostatic repulsion within the viral RNA. Consistent with this idea, electron microscopy images show that proteolysis introduces asymmetry into the TCV capsid and allows initial extrusion of the genome from a defined site. The apparent formation of polysomes in wheat germ extracts suggests that subsequent uncoating is linked to translation. The implication is that the viral RNA and its capsid play multiple roles during primary infections, consistent with ribosome-mediated genome uncoating to avoid host antiviral activity. PMID- 22306465 TI - Structural, bioinformatic, and in vivo analyses of two Treponema pallidum lipoproteins reveal a unique TRAP transporter. AB - Treponema pallidum, the bacterial agent of syphilis, is predicted to encode one tripartite ATP-independent periplasmic transporter (TRAP-T). TRAP-Ts typically employ a periplasmic substrate-binding protein (SBP) to deliver the cognate ligand to the transmembrane symporter. Herein, we demonstrate that the genes encoding the putative TRAP-T components from T. pallidum, tp0957 (the SBP), and tp0958 (the symporter), are in an operon with an uncharacterized third gene, tp0956. We determined the crystal structure of recombinant Tp0956; the protein is trimeric and perforated by a pore. Part of Tp0956 forms an assembly similar to those of "tetratricopeptide repeat" (TPR) motifs. The crystal structure of recombinant Tp0957 was also determined; like the SBPs of other TRAP-Ts, there are two lobes separated by a cleft. In these other SBPs, the cleft binds a negatively charged ligand. However, the cleft of Tp0957 has a strikingly hydrophobic chemical composition, indicating that its ligand may be substantially different and likely hydrophobic. Analytical ultracentrifugation of the recombinant versions of Tp0956 and Tp0957 established that these proteins associate avidly. This unprecedented interaction was confirmed for the native molecules using in vivo cross-linking experiments. Finally, bioinformatic analyses suggested that this transporter exemplifies a new subfamily of TPATs (TPR-protein-associated TRAP-Ts) that require the action of a TPR-containing accessory protein for the periplasmic transport of a potentially hydrophobic ligand(s). PMID- 22306466 TI - The Hill model for binding myosin S1 to regulated actin is not equivalent to the McKillop-Geeves model. AB - The Hill two-state cooperativity model and the McKillop-Geeves (McK-G) three state model predict very similar binding traces of myosin subfragment 1 (S1) binding to regulated actin filaments in the presence and absence of calcium, and both fit the experimental data reasonably well [Chen et al., Biophys. J., 80, 2338-2349]. Here, we compared the Hill model and the McK-G model for binding myosin S1 to regulated actin against three sets of experimental data: the titration of regulated actin with S1 and the kinetics of S1 binding of regulated actin with either excess S1 to actin or excess actin to S1. Each data set was collected for a wide range of specified calcium concentrations. Both models were able to generate reasonable fits to the time course data and to titration data. The McK-G model can fit all three data sets with the same calcium-concentration sensitive parameters. Only K(B) and K(T) show significant calcium dependence, and the parameters have a classic pCa curve. A unique set of the Hill model parameters was extremely difficult to estimate from the best fits of multiple sets of data. In summary, the McK-G cooperativity model more uniquely resolves parameters estimated from kinetic and titration data than the Hill model, predicts a sigmoidal dependence of key parameters with calcium concentration, and is simpler and more suitable for practical use. PMID- 22306467 TI - Structure of the ultra-high-affinity colicin E2 DNase--Im2 complex. AB - How proteins achieve high-affinity binding to a specific protein partner while simultaneously excluding all others is a major biological problem that has important implications for protein design. We report the crystal structure of the ultra-high-affinity protein-protein complex between the endonuclease domain of colicin E2 and its cognate immunity (Im) protein, Im2 (K(d)~10(-)(15) M), which, by comparison to previous structural and biophysical data, provides unprecedented insight into how high affinity and selectivity are achieved in this model family of protein complexes. Our study pinpoints the role of structured water molecules in conjoining hotspot residues that govern stability with residues that control selectivity. A key finding is that a single residue, which in a noncognate context massively destabilizes the complex through frustration, does not participate in specificity directly but rather acts as an organizing center for a multitude of specificity interactions across the interface, many of which are water mediated. PMID- 22306468 TI - Interaction of J-protein co-chaperone Jac1 with Fe-S scaffold Isu is indispensable in vivo and conserved in evolution. AB - The ubiquitous mitochondrial J-protein Jac1, called HscB in Escherichia coli, and its partner Hsp70 play a critical role in the transfer of Fe-S clusters from the scaffold protein Isu to recipient proteins. Biochemical results from eukaryotic and prokaryotic systems indicate that formation of the Jac1-Isu complex is important for both targeting of the Isu for Hsp70 binding and stimulation of Hsp70's ATPase activity. However, in apparent contradiction, we previously reported that an 8-fold decrease in Jac1's affinity for Isu1 is well tolerated in vivo, raising the question as to whether the Jac1:Isu interaction actually plays an important biological role. Here, we report the determination of the structure of Jac1 from Saccharomyces cerevisiae. Taking advantage of this information and recently published data from the homologous bacterial system, we determined that a total of eight surface-exposed residues play a role in Isu binding, as assessed by a set of biochemical assays. A variant having alanines substituted for these eight residues was unable to support growth of a jac1-Delta strain. However, replacement of three residues caused partial loss of function, resulting in a significant decrease in the Jac1:Isu1 interaction, a slow growth phenotype, and a reduction in the activity of Fe-S cluster-containing enzymes. Thus, we conclude that the Jac1:Isu1 interaction plays an indispensable role in the essential process of mitochondrial Fe-S cluster biogenesis. PMID- 22306469 TI - Perceptions of the host country's food culture among female immigrants from Africa and Asia: aspects relevant for cultural sensitivity in nutrition communication. AB - OBJECTIVE: To explore how female immigrants from Africa and Asia perceive the host country's food culture, to identify aspects of their original food culture they considered important to preserve, and to describe how they go about preserving them. DESIGN: Qualitative in-depth interviews. SETTING: Oslo, Norway. PARTICIPANTS: Twenty one female immigrants from 11 African and Asian countries, residing in areas of Oslo with a population having a low-to-middle socioeconomic status and a high proportion of immigrants. Participants varied in years of residence, employment status, and marital status. ANALYSIS: Analysis of the interviews was guided by a phenomenological approach. RESULTS: Participants emphasized the importance of preserving aspects of their original food cultures and related these aspects to taste, preparation effort and method, and adherence to religious dietary rules. They often perceived the food of the host country as "tasteless and boring." The authors observed strict, flexible, or limited continuity with the original food culture. Some elements that possibly influenced participants' degree of continuity are indicated. CONCLUSIONS AND IMPLICATIONS: Immigrants may strive to preserve aspects of their original food culture after immigration. Nutrition communication becomes more culturally sensitive when it takes such aspects into account. PMID- 22306470 TI - Ghana's herbal market. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plant markets not only provide a snapshot of a country's medicinal flora, they also reflect local health concerns and the importance of traditional medicine among its inhabitants. This study aimed to describe and quantify the Ghanaian market in herbal medicine, and the diversity of the species traded, in order to evaluate their economic value. MATERIALS AND METHODS: Initial visual surveys on the markets were followed by a detailed quantitative survey of 27 stalls in August 2010. Market samples were processed into herbarium vouchers and when possible matched with fertile vouchers from the field. RESULTS: We encountered 244 medicinal plant products, representing 186-209 species. Fourteen species were sold at more than 25% of the market stalls. Seeds and fruits that doubled as spice and medicine (Xylopia aethiopica, Monodora myristica, Aframomum melegueta) were in highest demand, followed by the medicinal barks of Khaya senegalensis and Pteleopsis suberosa. Plants sold at the market were mostly used for women's health, in rituals, as aphrodisiacs and against sexually transmitted diseases. An estimated 951tons of crude herbal medicine were sold at Ghana's herbal markets in 2010, with a total value of around US$ 7.8 million. Between 20 and 30% of the Ghanaian medicinal flora was encountered during this survey. Roots were less dominant at the market than in dryer parts of Africa. Tons of Griffonia simplicifolia and Voacanga africana seeds and Fadogia agrestis bark are exported annually, but data on revenues are scanty. None of these species were sold on the domestic market. CONCLUSION: Our quantitative market survey reveals that the trade in Ghanaian herbal medicine is of considerable economic importance. Regarding the specific demand, it seems that medicinal plants are used to complement or substitute Western medicine. Further research is needed on the ecological impact of medicinal plant extraction. PMID- 22306471 TI - Suppression of peeling during the release of O-glycans by hydrazinolysis. AB - The analysis of O-glycans is essential for better understanding their functions in biological processes. Although many techniques for O-glycan release have been developed, the hydrazinolysis release method is the best for producing O-glycans with free reducing termini in high yield. This release technique allows the glycans to be labeled with a fluorophore and analyzed by fluorescence detection. Under the hydrazinolysis release conditions, a side reaction is observed and causes the loss of monosaccharides from the reducing terminus of the glycans (known as peeling). Using bovine fetuin (because it contains the sialylated O glycans most commonly found on biopharmaceuticals) and bovine submaxillary gland mucin (BSM), here we demonstrate that peeling can be greatly reduced when the sample is buffer exchanged prior to hydrazinolysis with solutions of either 0.1% trifluoroacetic acid (TFA) or low-molarity (100, 50, 20, and 5 mM) ethylenediaminetetraacetic acid (EDTA). The addition of calcium chloride to fetuin resulted in an increase in peeling, whereas subsequent washing with EDTA abolished this effect, suggesting a role of calcium and possibly other cations in causing peeling. The presented technique for sample preparation prior to hydrazinolysis greatly reduces the level of undesirable cleavage products in O glycan analysis and increases the robustness of the method. PMID- 22306472 TI - Designing isothermal titration calorimetry experiments for the study of 1:1 binding: problems with the "standard protocol". AB - Literature recommendations for designing isothermal titration calorimetry (ITC) experiments to study 1:1 binding, M+X -->/<-- MX, are not consistent and have persisted through time with little quantitative justification. In particular, the "standard protocol" employed by most workers involves 20 to 30 injections of titrant to a final titrant/titrand mole ratio (R(m)) of ~ 2-a scheme that can be far from optimal and can needlessly limit applicability of the ITC technique. These deficiencies are discussed here along with other misconceptions. Whether a specific binding process can be studied by ITC is determined less by c (the product of binding constant K and titrand concentration [M](0)) than by the total detectable heat q(tot) and the extent to which M can be converted to MX. As guidelines, with 90% conversion to MX, K can be estimated within 5% over the range 10 to 10(8)M(-1) when q(tot)/sigma(q)~700, where sigma(q) is the standard deviation for estimation of q. This ratio drops to ~150 when the stoichiometry parameter n is treated as known. A computer application for modeling 1:1 binding yields realistic estimates of parameter standard errors for use in protocol design and feasibility assessment. PMID- 22306473 TI - Cell-free synthesis of cytochrome bo(3) ubiquinol oxidase in artificial membranes. AB - The analysis of membrane proteins is notoriously difficult because isolation and detergent-mediated reconstitution often results in compromising the protein structure and function. We introduce a novel strategy of combining a cell-free expression method for synthesis of a protein species coping with one of the most important obstacles in membrane protein research-preserving the structural functional integrity of a membrane protein species and providing a stable matrix for application of analytical tools to characterize the membrane protein of interest. We address integration and subsequent characterization of the cytochrome bo(3) ubiquinol oxidase (Cyt-bo(3)) from de novo synthesis without the effort of conventional cell culture, isolation, and purification procedures. The experimental output supports our idea of a suitable platform for in vitro protein synthesis and functional integration into a membrane-mimicking structure. We show the compatibility of different concepts of in vitro synthesis toward biosensor applicability by the example of Cyt-bo(3) protein expression. Our results obtained from in vitro synthesized proteins displayed similar behavior to proteins isolated from the cellular context. Overall, our approach is suitable for the in vitro expression of "complex" protein species such as Cyt-bo(3), which can be reproducible and stably synthesized and preserved in robust, synthetic planar membrane architecture. PMID- 22306474 TI - Differential microRNA expression analysis in blastocysts by whole mount in situ hybridization and reverse transcription quantitative polymerase chain reaction on laser capture microdissection samples. AB - There is cumulating evidence that microRNAs (miRNAs) are important regulators of pluripotency and differentiation and, hence, of early lineage segregation in embryo development. To unravel the function of specific miRNAs, it is important not only to analyze miRNA expression in the entire blastocyst but also to determine the site and level of expression in the inner cell mass (ICM) versus trophectoderm (TE). A new strategy has been developed for miRNA expression analysis in ICM and TE using two complementary techniques. By whole mount in situ hybridization (WISH), it was visualized that bta-miR-155 is mainly expressed in the ICM. However, WISH does not provide quantitative data on expression differences between the two cell types. By reverse transcription quantitative polymerase chain reaction (RT-qPCR) on ICM and TE isolates taken from single blastocysts with laser capture microdissection (LCM), it was quantified that bta miR-155 was 50-fold higher expressed in ICM than in TE. The possibility to quantify both miRNAs and messenger RNAs (mRNAs) in LCM samples offers the opportunity to analyze the expression of both miRNAs and potential targets in one sample. This article shows that a combination of WISH with LCM and subsequent RT qPCR is a robust strategy to qualitatively and quantitatively analyze differential miRNA expression in discrete cell types of a single blastocyst. PMID- 22306475 TI - Supraspinal injection of Substance P attenuates allodynia and hyperalgesia in a rat model of inflammatory pain. AB - The neuropeptide Substance P (SP), that has a high affinity for the neurokinin 1 (NK1) receptor, is involved in modulation of pain transmission. Although SP is thought to have excitatory actions and promote nociception in the spinal cord, the peptide induces analgesia at the supraspinal level. The aim of this study was to evaluate the role of supraspinal SP and the NK1 receptor in inflammatory pain induced by injection of carrageenan in the hind paw of the rat. There are two nociceptive behavioral responses associated with this pain state: mechanical allodynia and heat hyperalgesia. Because the NK1 receptor colocalizes with the MOP receptor in supraspinal sites involved in pain modulation, we also decided to study the possible involvement of the opioid system on SP-induced analgesia. We found that treatment with SP, at doses of 3.5, 5 and 7 MUg/5 MUl/rat i.c.v., clearly showed inhibition of allodynia and hyperalgesia. Pretreatment with the selective NK1 antagonist L-733,060 (10mg/kg i.p.) blocked the SP-induced analgesia, suggesting the involvement of the NK1 receptor. This SP-induced analgesia was significantly reduced by administration of the opioid antagonist naloxone (3mg/kg s.c.). This reduction occurred when SP was administered either before or after the carrageenan injection. These results suggest a significant antinociceptive role for SP and the NK1 receptor in inflammatory pain at the supraspinal level, possibly through the release of endogenous opioids. PMID- 22306476 TI - Characterization of GnRH-related peptides from the Pacific oyster Crassostrea gigas. AB - Gonadotropin-releasing hormone (GnRH), a key neuropeptide regulating reproduction in vertebrates has now been characterized in a number of non-vertebrate species. Despite the demonstration of its ancestral origin, the structure and the function of this family of peptides remain poorly known in species as distant as lophotrochozoans. In this study, two GnRH-related peptides (Cg-GnRH-a and CgGnRH G) were characterized by mass spectrometry from extracts of the visceral ganglia of the Pacific oyster Crassostrea gigas. These peptides showed a high degree of sequence identity with GnRHs of other mollusks and annelids and to a lesser extent with those of vertebrates or with AKH and corazonins of insects. Both the mature peptides and the transcript encoding the precursor protein were exclusively expressed in the visceral ganglia. Significant differences in transcriptional activity of Cg-GnRH encoding gene were recorded in the ganglia along the reproductive cycle and according to trophic conditions with a higher level in fed animals compared to starved animals. This suggests the involvement of Cg-GnRHs as synchronizers of nutritional status with energy requirements during reproduction in oyster. Evidence for a role of Cg-GnRHs as neuroregulators and as neuroendocrine factors in bivalve is discussed. PMID- 22306477 TI - Mechanism of action and specificity of antimicrobial peptides designed based on buforin IIb. AB - Buforin IIb-a synthetic analog of buforin II that contains a proline hinge between the two alpha-helices and a model alpha-helical sequence at the C terminus (3* RLLR)-is a potent cell-penetrating antimicrobial peptide. To develop novel antimicrobial peptides with enhanced activities and specificity/therapeutic index, we designed several analogs (Buf III analogs) by substitutions of amino acids in the proline hinge region and two alpha-helices of buforin IIb, and examined their antimicrobial activity and mechanism of action. The substitution of hydrophobic residues ([F(6)] and [V(8)]) in the proline hinge region with other hydrophobic residues ([W(6)] and [I(8)]) did not affect antimicrobial activity, while the substitution of the first four amino acids RAGL with a model alpha-helical sequence increased the antimicrobial activity up to 2-fold. Like buforin IIb, Buf III analogs penetrated the bacterial cell membranes without significantly permeabilizing them and were accumulated inside Escherichia coli. Buf III analogs were shown to bind DNA in vitro and the DNA binding affinity of the peptides correlated linearly with their antimicrobial potency. Among the Buf III analogs, the therapeutic index of Buf IIIb and IIIc (RVVRQWPIG[RVVR](3) and KLLKQWPIG[KLLK](3), respectively) were improved 7-fold compared to that of buforin IIb. These results indicate that Buf III analogs appear to be promising candidates for future development as novel antimicrobial agents. PMID- 22306478 TI - Raised inflammatory markers. PMID- 22306479 TI - Efficacy and safety of enoxaparin versus unfractionated heparin during percutaneous coronary intervention: systematic review and meta-analysis. AB - OBJECTIVE: To determine the efficacy and safety of enoxaparin compared with unfractionated heparin during percutaneous coronary intervention. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline and Cochrane database of systematic reviews, January 1996 to May 2011. STUDY SELECTION: Randomised and non-randomised studies comparing enoxaparin with unfractionated heparin during percutaneous coronary intervention and reporting on both mortality (efficacy end point) and major bleeding (safety end point) outcomes. DATA EXTRACTION: Sample size, characteristics, and outcomes, extracted independently and analysed. DATA SYNTHESIS: 23 trials representing 30,966 patients were identified, including 10,243 patients (33.1%) undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction, 8750 (28.2%) undergoing secondary percutaneous coronary intervention after fibrinolysis, and 11,973 (38.7%) with non-ST elevation acute coronary syndrome or stable patients scheduled for percutaneous coronary intervention. A total of 13,943 patients (45.0%) received enoxaparin and 17,023 (55.0%) unfractionated heparin. Enoxaparin was associated with significant reductions in death (relative risk 0.66, 95% confidence interval 0.57 to 0.76; P<0.001), the composite of death or myocardial infarction (0.68, 0.57 to 0.81; P<0.001), and complications of myocardial infarction (0.75, 0.6 to 0.85; P<0.001), and a reduction in incidence of major bleeding (0.80, 0.68 to 0.95; P=0.009). In patients who underwent primary percutaneous coronary intervention, the reduction in death (0.52, 0.42 to 0.64; P<0.001) was particularly significant and associated with a reduction in major bleeding (0.72, 0.56 to 0.93; P=0.01). CONCLUSION: Enoxaparin seems to be superior to unfractionated heparin in reducing mortality and bleeding outcomes during percutaneous coronary intervention and particularly in patients undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction. PMID- 22306480 TI - Kidney failure with a diagnostic chest radiograph. PMID- 22306481 TI - Enoxaparin for anticoagulation in patients undergoing percutaneous coronary intervention. PMID- 22306482 TI - Critics of the NHS reforms have lost sight of what they can deliver, hears conference. PMID- 22306483 TI - Psychiatric drugs are not inferior to other drugs, review concludes. PMID- 22306484 TI - RCGP calls for withdrawal of health bill despite 137 new amendments. PMID- 22306485 TI - A proton magnetic resonance spectroscopy study in schizoaffective disorder: comparison of bipolar disorder and schizophrenia. AB - The aim of this study was to compare schizoaffective disorder, bipolar disorder and schizophrenia based on (1)H-MRS metabolite values in dorsolateral prefrontal cortex and executive functions. The subjects comprised 15 patients with bipolar disorder type I (BD), 15 with schizophrenia (SCH), 15 with schizoaffective disorder (SAD) and 15 healthy controls. We performed proton magnetic resonance spectroscopy ((1)H-MRS) of the dorsolateral prefrontal cortex (DLPFC) bilaterally. Levels of N-acetyl aspartate (NAA), choline-containing compounds (Cho) and creatine-containing compounds (Cr) were measured in the DLPFC using (1)H-MRS. We administered the Wisconsin Card Sorting Test (WCST) and the Stroop Test (ST) to evaluate executive functions. The SAD, BD and SCH patients had lower levels of NAA than the control group. The SAD and BD patients had low levels of Cho compared to the control group. The left DLPFC Cr levels in all of the patient groups and the right DLPFC Cr levels in the BD and SAD groups were lower than in the control group. The levels of NAA Cho and Cr were not related to executive functions and attention performance. Cr level were related to attention processes, only in SCH. Our results indicate that NAA levels are reduced in schizoaffective disorder, bipolar disorder and schizophrenia, but the reduction in the levels of NAA is not a distinctive feature among these three illnesses. Schizoaffective and bipolar disorders have similar features related to the levels of compounds containing Cho and Cr. This similarity may be related to these illnesses both having an affective basis. PMID- 22306486 TI - Admit all anticoagulated head-injured patients? A million dollars versus your dime. You make the call. PMID- 22306487 TI - Opposing action of conantokin-G on synaptically and extrasynaptically-activated NMDA receptors. AB - Synaptic and extrasynaptic activation of the N-methyl-D-aspartate receptor (NMDAR) has distinct consequences on cell signaling and neuronal survival. Since conantokin (con)-G antagonism is NR2B-selective, which is the key subunit involved in extrasynaptic activation of the receptor, its ability to specifically elicit distinct signaling outcomes in neurons with synaptically or extrasynaptically-activated NMDARs was evaluated. Inhibition of Ca(2+) influx through extrasynaptic NMDAR ion channels was neuroprotective, as it effectively enhanced levels of activated extracellular signal-regulated kinase 1/2 (ERK1/2), activated cAMP response element binding protein (CREB), enhanced mitochondrial viability, and attenuated the actin disorganization observed by extrasynaptic activation of NMDARs. Conversely, the pro-signaling pathways stimulated by synaptically-induced Ca(2+) influx were abolished by con-G. Furthermore, subunit non-selective con-T was unable to successfully redress the impairments in neurons caused by extrasynaptically-activated NMDARs, thus indicating that NR2B-specific antagonists are beneficial for neuron survival. Neurons ablated for the NR2B subunit showed weak synaptic Ca(2+) influx, reduced sensitivity to MK-801 blockage, and diminished extrasynaptic current compared to WT and NR2A(-/-) neurons. This indicates that the NR2B subunit is an integral component of both synaptic and extrasynaptic NMDAR channels. Altogether, these data suggest that con-G specifically targets the NR2B subunit in the synaptic and extrasynaptic locations, resulting in the opposing action of con-G on differentially activated pools of NMDARs. PMID- 22306488 TI - Chronic arsenicosis in goats with special reference to its exposure, excretion and deposition in an arsenic contaminated zone. AB - Thirty goats were selected randomly from a village of Nadia district, West Bengal according to the previous reports of human being suffering from chronic arsenicosis. Environmental samples viz. drinking water, rice plants and grass used for goat and biological samples viz. blood, urine, faeces, hair and meat were collected to evaluate the arsenic status. It was found that arsenic concentration in both environmental and biological samples was significantly (p<0.01) higher rather than respective samples on control zone. Bio-concentration factor (BCF) and bio-transfer factor (BTF) are indicated to evaluate the subclinical toxicity in goat as they do not exhibit clinical manifestation like human beings. PMID- 22306489 TI - Challenges in drug delivery to tumors of the central nervous system: an overview of pharmacological and surgical considerations. AB - The majority of newly diagnosed brain tumors are treated with surgery, radiation, and the chemotherapeutic temozolomide. Development of additional therapeutics to improve treatment outcomes is complicated by the blood-brain barrier (BBB), which acts to protect healthy tissue from chemical insults. The high pressure found within brain tumors adds a challenge to local delivery of therapy by limiting the distribution of bolus injections. Here we discuss various drug delivery strategies, including convection-enhanced delivery, intranasal delivery, and intrathecal delivery, as well as pharmacological strategies for improving therapeutic efficacy, such as blood-brain barrier disruption. PMID- 22306490 TI - Prenatal exposure to perfluorooctanoate and risk of overweight at 20 years of age: a prospective cohort study. AB - BACKGROUND: Perfluoroalkyl acids are persistent compounds used in various industrial -applications. Of these compounds, perfluorooctanoate (PFOA) is currently detected in humans worldwide. A recent study on low-dose developmental exposure to PFOA in mice reported increased weight and elevated biomarkers of adiposity in postpubertal female offspring. OBJECTIVE: We examined whether the findings of increased weight in postpubertal female mice could be replicated in humans. METHODS: A prospective cohort of 665 Danish pregnant women was recruited in 1988-1989 with offspring follow-up at 20 years. PFOA was measured in serum from gestational week 30. Offspring body mass index (BMI) and waist circumference were recorded at follow-up (n = 665), and biomarkers of adiposity were quantified in a subset (n = 422) of participants. RESULTS: After adjusting for covariates, including maternal pre-pregnancy BMI, smoking, education, and birth weight, in utero exposure to PFOA was positively associated with anthropometry at 20 years in female but not male offspring. Adjusted relative risks comparing the highest with lowest quartile (median: 5.8 vs. 2.3 ng/mL) of maternal PFOA concentration were 3.1 [95% confidence interval (CI): 1.4, 6.9] for overweight or obese (BMI >= 25 kg/m2) and 3.0 (95% CI: 1.3, 6.8) for waist circumference > 88 cm among female offspring. This corresponded to estimated increases of 1.6 kg/m2 (95% CI: 0.6, 2.6) and 4.3 cm (95% CI: 1.4, 7.3) in average BMI and waist circumference, respectively. In addition, maternal PFOA concentrations were positively associated with serum insulin and leptin levels and inversely associated with adiponectin levels in female offspring. Similar associations were observed for males, although point estimates were less precise because of fewer observations. Maternal perfluorooctane sulfonate (PFOS), perfluorooctane sulfonamide (PFOSA), and perfluorononanoate (PFNA) concentrations were not independently associated with offspring anthropometry at 20 years. CONCLUSIONS: Our findings on the effects of low-dose developmental exposures to PFOA are in line with experimental results suggesting obesogenic effects in female offspring at 20 years of age. PMID- 22306491 TI - Treatment of renal cell carcinoma in pregnancy: simultaneous nephron-sparing surgery and Caesarian section (case report). AB - We present a case of a 33-year-old pregnant woman with renal cell carcinoma diagnosed at 24 weeks of gestational age. Simultaneous nephron sparing surgery (NSS) and Caesarean section (CS) was performed at 33 weeks of gestation. The successful cases of radical nephrectomy performed in pregnancy have been reported earlier however, we believe this is the first case of NSS and CS performed simultaneously. This approach can be used in the second and third trimester of pregnancy. PMID- 22306492 TI - Health-related quality of life after radical nephrectomy and kidney donation. AB - The health-related quality of life (HRQoL) concept is frequently applied for the assessment of surgical or other treatment modalities. We evaluated the HRQoL of 57 kidney donors and compared it to: 120 age and sex matched healthy individuals; and 52 patients who underwent nephrectomy due to renal tumor. The Short Form-36 (SF-36), Giessen Subjective Complaints List (GBB-24) and Zerssen's Mood Scale (Bf S) questionnaires have been used for this purpose. The mean scores of different domains have been calculated for all three questionnaires and compared between the groups. In three out of eight SF-36 items ("Social function", "Bodily pain" and "Vitality") the donors scored significantly better than the controls and patients. In all five GBB-24 items the donors scored higher than the controls and patients. For the "Gastric complaints" the difference was significant. The mood analysis has shown significant differences between the groups in favour of the donors. The HRQoL of living kidney donors is not different from that of healthy subjects and significantly better than HRQoL of urological patients after nephrectomy. The HRQol of living kidney donors and healthy individuals is similar and better than HRQol of the patients operated due to the medical indications. Further prospective studies are needed to increase our knowledge of factors influencing HRQol of the living kidney donors and patients after nephrectomy. PMID- 22306493 TI - [Metastasizing in thyroid gland cancer]. AB - The aim of the research was the analysis of metastasis in patients with thyroid carcinoma in Armenia in 1999-2011. Case histories of 529 patients with thyroid cancer from 1999-2011 were investigated. It was found that the prognostic value of regional metastases differs considerably. In cases of differentiated carcinomas the regional metastases are not regarded as a significant factor of the prognosis, because the majority of the affected lymph nodes is removed by the qualified surgeons during the operation, and the others (not revealed or micrometastases), due to ability to accumulate radio iodine, can be liquidated in the postoperative course of radio iodine therapy. The prognosis is less favorable in regional metastasizing at patients with other types of thyroid cancer. Almost the half of the patients who have died because of thyroid carcinoma had the regional and distant metastases. The index of metastasis in thyroid cancer in rural settlements is higher, than in urban in Armenia. The frequency of metastasizing is higher in elderly patients. PMID- 22306494 TI - [Problems of early clinical diagnosis of thyroid cancer]. AB - The aim of the study was the evaluation of early diagnosis of thyroid cancer and its impact on the management of these patients. Hospital-based study of 113 primary thyroid cancer cases diagnosed between 1999 and 2011 were evaluated in this report. The study revealed the crucial importance of accurate information about the subtypes of thyroid tumors in the management of these patients and the prognosis of thyroid cancer. There is need for reproducible biomarker that correlates directly with the presence or progression of thyroid cancer. PMID- 22306495 TI - [Some considerations of immune metabolism at preeclampsia]. AB - The goal of the work is to determine several aspects of abnormalities and a part of immune metabolism in preeclampsia. In peripheral blood serum of all pregnant women at 20th week of gestation relative content of T-lymphocyte subpopulations, active T-lymphocytes and natural killers (NK) were detected by the method of indirect immunofluorescence and in cyto-toxic test using monoclonal antibodies to CD4 and CD84, CD 16 (T-cell markers of HLA-DR antigen of second class of MHC (marker of active T-lymphocytes, "ICN Pharmaceutical", USA). According study results it can be concluded that at preeclampsia a content of NK cells in peripheral blood of pregnant women increases in the end of the second and early in the third trimesters on the background of significant decrease of general CD4 lymphocyte subpopulation. Received data allow to suppose that activation of natural killer cells (NK-cells) may be caused by the activation of cytotoxic Th-1 cells and their cytokines. PMID- 22306496 TI - Alteration of functional state of peripheral blood erythrocytes in women of different age groups at dislipidemia conditions. AB - The aim of the study was identification of statistically reliable correlations and the cause-effect relationships between viability of red blood cells and dislipidema parametres and/or metabolic disorders, induced by age related alterations of estrogen content, in women of different ages (reproductive, menopausal) On the basis of the analysis of research results we can conclude that in the different age groups of women with atherosclerosis-induced cardiovascular diseases revealed estrogen-related dependence between Tg-s and HDL content, functional status of phereperial blood erytrotcites and severity of dislipidemia. The aterogenic index Tg/HD proved to be sensitive marker of dislipidemia in reproductive aging women, but does't reflect disorders of lipid metabolism in postmenosal women. It was proved the existence of reliable corelation between red blood cells dysfunction indicator, spherulation quality, and atherogenic index Tg/HDL highlights; however, the correlation coefficient is 2 times higher in the reproductive age as in menopause. Spherulation quality of red blood cells at low HDL content showd fast growth rate in reproductive-aged women, and was unsensetive to HDL content in postmenopasal women. It was concluded that age-related lack of estrogens in postmenopausal women indirectly contributes to decrease protection of red blood cells against oxidative damage, reduces their deformabelity and disturbances the rheological properties. So, Spherulation quality of red blood cells may be used as a diagnostic marker of severity of atherosclerosis. PMID- 22306497 TI - Stenting of the left main bronchus in cicatrical post-TB bronchial stenosis (case report). AB - The primary treatment of endobronchial tuberculosis complicated by bronchial stenosis is antituberculous chemotherapy. Surgical resection and bronchoplastic reconstruction has long been the standard treatment. However, bronchoscopic intervention is essential to restore the patency of the involved bronchus and controlling TB. To our best knowledge this is a first report of bronchial stenting in Georgian Republic. We performed this procedure in cooperation with interventional cardiologists from Cardiac Catheterization Laboratory "HELSY T.E." Ltd. which have wide experience in stenting manipulations. A 24-year-old woman, after treatment with antituberculous medications for pulmonary tuberculosis, suffered by cough, dyspnea, wheezing. CT scan showed stricture of the left main bronchus starting from bifurcation to the end and having a lumen diameter 2mm. Bronchoscopic examination revealed focal narrowing to pinhole size to the left main bronchus with severe fibrotic changes. We decided to perform endobronchial stenting. Under general anesthesia, balloon-expendable, metallic, non-covered stent (Medtronic) was inserted across the stenotic lesion and was expanded under the pressure of 9 atmospheres using Indeflator Perouse Medical. Bronchography, taken immediately after stent insertion, showed an expanded left main bronchus. Postoperatively the patient did well. Chest radiographs taken after 6 days demonstrating a fully expanded stent, mediastinal repositioning towards the midline and normal aeration of the left lung. Patient's dyspnea was much improved. The patient has now been asymptomatic for 3 months. In conclusion, this case describes a patient with a cicatrical post-TB bronchial stenosis that was effectively treated by bronchoscopic stenting, which is alternative to surgical resection thus avoiding unwarranted thoracotomies and providing quality of life. PMID- 22306498 TI - [Case study with a gunshot fracture of lower extremities and damage of popliteal artery (case report)]. AB - Severe vascular gunshot injury (popliteal artery damage) and fractures of both low extremities are causes traumatic shock (stage III) and anemia in a 32 years female patient. Being the victim of crime, the patient for 5 hours was in a life threatening condition that could develop the multiple organ system failure (MOSF) as a result of tissue ischemia and reperfusion and acute irreversible shock. There was an urgent necessity to perform three immediate operations at the same time. Successful recovery required rapid control of the inciting event (i.e., maintenance of effective hemodynamic stability and the body's ability to protect its vital organs, choice of the type of anesthesia with certain anesthetics) facilitated by resuscitative therapy directed toward minimizing the overall "dose" of shock. Oxybutirate sodium (a GABA analog, the only one narcotic drug and a natural metabolite of body) administered intravenously as a hypnotic agent and an important component of intensive care as well have had clearly anti-shock and antihypoxant effects. Rapid improving of circulation and using of medications with wide range of anti-stress action (such as oxybutirate sodium, dexamethazone and glucose) assisted successful resuscitation and possibility to perform three operations (duration: 6 hours and 45 minutes). An increasing emphasis was being placed on prevention of MOSF, including 1) maintenance of tissue oxygenation; 2) using above-mentioned anti-stress and antihypoxant medicines with mutually supportive effects and 3) infection control. PMID- 22306499 TI - The serum level of interleukin-12 among patients with HCV infection. AB - The aim of investigation was to study cytokine-producing ability of blood immune cells in type of viral hepatitis C, correlation with the degree of hepatic lesion and liver cirrhosis. 130 patients were investigated: 20 with acute hepatitis C; 38 with chronic hepatitis C; 72 with cirrhosis: among them 10 with Stage A, 14 with Stage B and 48 with Stage C. Also we used 30 healthy people as the controls. The study demonstrates significant changes of cytokine-producing ability of blood immune cells type of viral hepatitis C, correlation with the degree of hepatic lesion and liver cirrhosis. The serum contents of IL-12 in chronic HCV patients is higher than in patients with acute HCV infection and in patients with liver cirrhosis The results showed that various types of acute, chronic viral hepatitis C and stages of cirrhosis were associated with misbalance in production of proinflammatory cytokine, i. e. a rise of interleukin-12 concentration versus the controls., which were the most prominent in cases of severe hepatic lesion. PMID- 22306500 TI - Depression as a risk factor for arterial hypertension. AB - The aim of the subject is to represents the connection of the Arterial Hypertension and thrombocyte number in blood and to find prevention ways. A clinical case of depression symptoms as outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) is a disorder with both physical and mental characteristics that negatively disrupts an individual's ability to function day to day in social and work environments. According to the DSM, real depression is a condition of this nature that lasts for more than two weeks. The subject is actual because Arterial Hypertension according to WHO's data's is one the 1stplace, while Depression - one the 2nd.According to Georgian Disease Controlling and Medical Statistic National Centre data's, depression is characterized from 15% to 25% of people. We've searched for the clinical methods in Batumi Republic Hospital departments. 30 patient is studied by us - 15 women and 15 men. Among them, 20 patients was fallen ill with Arterial Hypertension, 5 with Ischemic insult and 5 - with Discirculating Encephalopathy. We've the question are of Beck. According to which we were able to ascertain the depression quality. The question are consists of 21 questions; by them it was possible to ascertain depression qualities light, medium and complex. The depression quality was defined as follows: the absence of depression in 13%; mild depression in 17%; medium - 30% and severe in 60%. Thus, Depression quality is very high in people with Arterial Hypertension. The number of thrombocyte is high also. Thrombocytes depression causes significant changes in the function, Thrombocytes Activation, Thrombosis increases the risk. So, it's necessary to treat this patient with Antithrombotic medicines and Antidepressants. That will contribute to solving the problem. PMID- 22306501 TI - [Serum amyloid a protein concentrations in patients with familial Mediterranean fever]. AB - AIM: the determination of serum amyloid A (SAA) protein concentrations in FMF patients: the colchicine-resistant patients and the patients responded to the different doses of colchicine, and estimation of the risk of the amyloidosis development in these patients. SAA concentration was measured in 58 FMF patients: 23 colchicine-resistant patients without amyloidosis and 35 patients responded to the different doses of colchicine also without amyloidosis as a group of comparison. Serum SAA concentration was measured by ELISA (Enzyme Linked-Immuno Sorbent-Assay) method using "ANOGEN" kit (Canada). Serum SAA concentration was the same in both groups of the patients: colchicine-resistant patients and patients responded to the different doses of colchicine. The findings of our study indicate that the risk of the amyloidosis development is the same in colchicine-resistant patients and patients responded to the different doses of colchicine. PMID- 22306502 TI - [The pyretroind pesticides lambda-cigalothrines influence on composition of free aminoacids in tissue of fish in Alazani River]. AB - The aim of the research was to study toxic effect of lambda-cigalothrin, on quantitative contents of free amino acid in muscle, liver and in brain of fishes in r. Alazani. It was found that under the action of lambda-cigalothrin total amount of free amino acid in fish's tissue was increasing, contents of glycine, asparagine and glutamine acids, alanine and cysteine also increased. Increasing of glutamine and asparagines acids content in muscle and liver of fish goes with the dissimilation of other amino acids through the process of their deaminization by glutamate dehydrogenation system. Increasing the alanine content is indicative of reinforcement of transamination processes. Decrease of phenylalanine, valine, glycine and the other amino acids content is explained by reinforcement of amino acids catabolism in condition of pesticide load, as it occurs in condition of fishes' intoxication by phenols. PMID- 22306503 TI - Effects of the uncompetitive NMDA receptor antagonist memantine on spatial memory in medial septal lesioned rats. AB - These experiments examined the effects of acute administration of memantine (2.5 or 5 mg/kg) or saline on spatial memory and learning process within single sessions, on place versions of food-rewarded maze in MS electrolytic lesioned and sham-lesioned rats. Sham-lesioned rats trained in the place task learned more rapidly than did MS electrolytic lesioned rats. This fact certifies for obvious deficit of the place learning performance strategy in the MS-lesioned rats. The results indicate that the drug-treated (5 mg/kg memantine) sham-lesioned rats exhibited significantly impaired performance relative to the saline controls in terms of trials-to-criterion (P<0.05). 2.5 mg/kg memantine administered 30 min before behavioral testing, did not affect performance in place learning task. 2.5 mg/kg and 5 mg/kg memantine administered before behavioral testing, did not improve performance in place learning task in MS electrolytic lesioned rats. Our experimental data support the interpretation that memantine does not produce intolerable side effects in human AD patients because it is being used at doses that are below the threshold for interacting with NMDA receptors. PMID- 22306504 TI - [The influence of the androgens on the process of the experimental diabetes and the activity of the synthesis of the nucleic acids in the male rats liver]. AB - The aim of this research is to study the dependence the gravity of diabetes course and the activity of the biosynthetical processes in the liver from the level of the sexual steroides in the male-rats blood on the model of the alloxan diabetes. The experiments were carried out on 80 male rats (weight 180-200g). The diabetes has been reproduced by the single injection of alloxan per 200mg/kg. The content of glucose, testosterone, estradiole and corticosterone have been determined in the blood of the animals. Activity of the syntheses of the nucleic acids in the liver has been researched by the radiometrical method on 14, 30, 45 and 90 days of the experiment. On all stages of the observation has been revealed the inverse relation between the concentration of the testosterone in the blood and the gravity of the experimental diabetes which was determined by the degree of hyperglycemya and the changes of the coefficient of sexual hormones ratio, the content of estradiol, corticosterone and activity of the syntheses of the nucleic acids in the tissue of the liver. The injection of the androgen during two week caused jump increasing the testosterone concentration, approaching the sexual steroids ratio to the norm, decreasing the glucose, estradiole, corticosterone content and also the reduction the nucleic acids syntheses activity in the liver. It was shown the positive influence of the androgens on development of the compensatory processes in the male rats, which course the decrease the experimental diabetes gravity. PMID- 22306505 TI - [Development of quantitative analyse method for determination of alkaloid cytisin in Spartium junceum L., growing in Georgia]. AB - The aim of the research was to develop a method for quantitative determination of cytisine in Spartium junceum L. We used the above-ground parts of plants. In developing a method of analysis we used the method of 3-phase extraction. In this case the best results were obtained in the system: chopped raw material - water solution of ammonia - chloroform. In this case, the amount of alkaloids extracted almost entirely from the plant and goes into the chloroform phase. Evaluation of the results was carried out by the validation. The method for determination of cytisine in raw product was proposed. The method comprises the following steps extraction of raw materials extracting chloroform phase and its evaporation, the translation of solids in methanol, the chromatographic separation cytisine and its fixation of the spectrophotometer method. The method is reproducible, has the required accuracy, is easy to analysis (less than 9 hours). PMID- 22306506 TI - Use of osteoplastic material to guide bone tissue regeneration deffect. AB - The goal of research was study of restoration processes in jaw-teeth bone defects by application of osteoplastic materials in the experiment. The experiment was performed over 32 white (6-12 month old) rats; the animals were divided into 2 groups; 16 animals were enrolled in the first group; the section was performed in the edge of lower jaw; the lower jaw body was revealed. Under the effect of the dental drilling machine and the # 1 cooling mean by the fissure bohrium (distilled water) the defect of the dimension of 2x2 mm was created; the defect was washed by 0/9% saline to remove the bone sawdust; the wound was sutured tightly, in layers. The second group of the experiment was staffed with 16 animals (main group); the similar bone defect of the size 2 x 2mm was created on the rat's jaw's body. After washing of modeled defect we inserted osteopathic materials PORESORB-TCP crystals with the size of 0,6-1.0 mm the wound was sutured tightly, in layers. After the 3-rd, 15-th, 30-th and 90-th days from the date of operation there was performed X-ray and morphological examination over the animals in the control as well as the main group. The analysis of the examination performed over the experimental materials showed that in the control group in samples taken at 90th day the defects were not completely restored. In the test group in samples taken at 90th day reparative regeneration is confirmed. This is stimulated by the factor that within the main group's animals the defect regeneration process is supported with the osteoplastic material PORESORB-TCP. PMID- 22306507 TI - [Some epidemiological aspects of breast cancer in Sheki-Zagatala economic region of Azerbaijan]. AB - Studied epidemiological aspects of breast cancer in the Sheki-Zagatala region of the republic with the establishment of the coefficient of extensity, intensity, total mortality, mortality rate, index of infestation, the 5-year survival. Found high levels of breast cancer in Zakatala region (32,7), exceeding 1,3 times the region-wide (24,8). The lowest recorded in Sheki region (16,0). The magnitude of the coefficient of mortality high level recorded in the Gabala region,a region wide rate exceeding 1,8 times (13,5%). It should be noted the high level of infestation rate in Sheki region (205,5), more than a region-wide by 1.3-fold (157,9). PMID- 22306508 TI - Oxidative stress, endogenous antioxidants, alcohol, and hepatitis C: pathogenic interactions and therapeutic considerations. AB - Hepatitis C virus (HCV) is a blood-borne pathogen that was identified as an etiologic agent of non-A, non-B hepatitis in 1989. HCV is estimated to have infected at least 170 million people worldwide. The majority of patients infected with HCV do not clear the virus and become chronically infected, and chronic HCV infection increases the risk for hepatic steatosis, cirrhosis, and hepatocellular carcinoma. HCV induces oxidative/nitrosative stress from multiple sources, including inducible nitric oxide synthase, the mitochondrial electron transport chain, hepatocyte NAD(P)H oxidases, and inflammation, while decreasing glutathione. The cumulative oxidative burden is likely to promote both hepatic and extrahepatic conditions precipitated by HCV through a combination of local and more distal effects of reactive species, and clinical, animal, and in vitro studies strongly point to a role of oxidative/nitrosative stress in HCV-induced pathogenesis. Oxidative stress and hepatopathogenesis induced by HCV are exacerbated by even low doses of alcohol. Alcohol and reactive species may have other effects on hepatitis C patients such as modulation of the host immune system, viral replication, and positive selection of HCV sequence variants that contribute to antiviral resistance. This review summarizes the current understanding of redox interactions of HCV, outlining key experimental findings, directions for future research, and potential applications to therapy. PMID- 22306509 TI - Damage to mtDNA in liver injury of patients with extrahepatic cholestasis: the protective effects of mitochondrial transcription factor A. AB - Oxidative stress and mitochondrial dysfunction are involved in the pathogenesis of chronic liver cholestasis. Mitochondrial DNA (mtDNA) is highly susceptible to oxidative stress and mtDNA damage leads to mitochondrial dysfunction. This study aimed to investigate the mtDNA alterations that occurred during liver injury in patients with extrahepatic cholestasis. Along with an increase in malondialdehyde (MDA) levels and a decrease in ATP levels, extrahepatic cholestatic patients presented a significant increase in mitochondrial 8-hydroxydeoxyguanosine (8 OHdG) levels and decreases in mtDNA copy number, mtDNA transcript levels, and mtDNA nucleoid structure. In L02 cells, glycochenodeoxycholic acid (GCDCA) induced similar damage to the mtDNA and mitochondria. In line with the mtDNA alterations, the mRNA and protein levels of mitochondrial transcription factor A (TFAM) were significantly decreased both in cholestatic patients and in GCDCA treated L02 cells. Moreover, overexpression of TFAM could efficiently attenuate the mtDNA damage induced by GCDCA in L02 cells. However, without its C-tail, DeltaC-TFAM appeared less effective against the hepatotoxicity of GCDCA than the wild-type TFAM. Overall, our study demonstrates that mtDNA damage is involved in liver damage in extrahepatic cholestatic patients. The mtDNA damage is attributable to the loss of TFAM. TFAM has mtDNA-protective effects against the hepatotoxicity of bile acid during cholestasis. PMID- 22306510 TI - Identification of Rhit as a novel transcriptional repressor of human Mpv17-like protein with a mitigating effect on mitochondrial dysfunction, and its transcriptional regulation by FOXD3 and GABP. AB - Mpv17-like protein (M-LP) is a protein that has been suggested to be involved in the metabolism of reactive oxygen species. To elucidate the molecular basis of M LP expression, we recently searched for regulatory elements of M-LP and identified a novel mouse KRAB-containing protein, Rhit (regulator of heat-induced transcription), as a repressor of the transcriptional regulation of M-LP. In this study, we identified zinc-finger protein 205 as a candidate human Rhit (RhitH) and subsequently confirmed its participation in transcriptional regulation of human M-LP (M-LPH). To clarify the functions of RhitH and M-LPH, we searched for cis-regulatory elements in the promoter region of RhitH and identified two transcription factors: forkhead box D3, as a negative regulatory element, and GA binding protein, one of the key regulators of the mitochondrial electron transport system, as a positive regulatory element. Additionally, it was demonstrated that knockdown of RhitH or overexpression of M-LPH reduces the generation of intracellular H(2)O(2) and loss of mitochondrial membrane potential caused by an inhibitor of the respiratory chain, antimycin A. These results suggest that M-LPH functions to protect cells from oxidative stress and/or initiation of the mitochondrial apoptotic cascade under stressed conditions. PMID- 22306511 TI - Coronal plane hip muscle activation in football code athletes with chronic adductor groin strain injury during standing hip flexion. AB - BACKGROUND: Groin pain arising from adductor muscle injury is common amongst football code athletes and can result in significant time lost from sporting participation. The associated motor control deficits are not well understood. AIMS: The aim of this study was to better understand the coronal plane muscle activation patterns associated with chronic adductor injury. METHODOLOGY: Measures of muscle activation at various stages of the standing hip flexion manoeuvre were made with surface electromyography and motion capture in 9 male football code subjects with chronic adductor injury, and 9 matched controls. RESULTS: The gluteus medius to adductor longus activation ratio was significantly reduced in subjects with groin pain when the injured leg was either moving (F = 64.3, p < 0.001) or in stance phase (F = 32.4, p < 0.001) when compared to activity-matched uninjured subjects, equating to a difference varying between 20 and 40% depending on phase of movement. These differences were particularly due to decreased abductor muscle activation. No significant differences between the uninjured and injured side of patients was found. CONCLUSION: Football code athletes with groin pain exhibit significantly altered coronal plane muscle activation with comparison to uninjured subjects. These findings need to be taken into account when planning rehabilitation for these athletes. PMID- 22306512 TI - Demethylation of TNFSF7 contributes to CD70 overexpression in CD4+ T cells from patients with systemic sclerosis. AB - The pathogenesis of systemic sclerosis (SSc) is still unclear. CD70, a B cell costimulatory molecule that interacts with CD27 during B-T cell contact, is overexpressed due to demethylation of its promoter regulatory elements in CD4+ T cells from patients with the following autoimmune diseases, namely systemic lupus erythematosus (SLE), subacute cutaneous lupus erythematosus (SCLE) and primary Sjogren's syndrome (pSS). However, as an autoimmune disease, it is unknown whether aberrant expression and methylation of CD70 occur in SSc CD4+ T cells. We aimed to investigate whether the aberrant expression and methylation status of CD70 occur in CD4+ T cells from patients with SSc. We found that the CD70 is overexpressed and the CD70 promoter region is demethylated in SSc CD4+ T cells. These findings suggest that demethylation of CD70 promoter region contributes to the overexpression of CD70 in CD4+ T cells and may contribute to autoimmune response in SSc. PMID- 22306513 TI - Probabilistic finite element analysis of a craniofacial finite element model. AB - We employed a probabilistic finite element analysis (FEA) method to determine how variability in material property values affects stress and strain values in a finite model of a Macaca fascicularis cranium. The material behavior of cortical bone varied in three ways: isotropic homogeneous, isotropic non-homogeneous, and orthotropic non-homogeneous. The material behavior of the trabecular bone and teeth was always treated as isotropic and homogeneous. All material property values for the cranium were randomized with a Gaussian distribution with either coefficients of variation (CVs) of 0.2 or with CVs calculated from empirical data. Latin hypercube sampling was used to determine the values of the material properties used in the finite element models. In total, four hundred and twenty six separate deterministic FE simulations were executed. We tested four hypotheses in this study: (1) uncertainty in material property values will have an insignificant effect on high stresses and a significant effect on high strains for homogeneous isotropic models; (2) the effect of variability in material property values on the stress state will increase as non-homogeneity and anisotropy increase; (3) variation in the in vivo shear strain values reported by Strait et al. (2005) and Ross et al. (2011) is not only due to variations in muscle forces and cranial morphology, but also due to variation in material property values; (4) the assumption of a uniform coefficient of variation for the material property values will result in the same trend in how moderate-to-high stresses and moderate-to-high strains vary with respect to the degree of non homogeneity and anisotropy as the trend found when the coefficients of variation for material property values are calculated from empirical data. Our results supported the first three hypotheses and falsified the fourth. When material properties were varied with a constant CV, as non-homogeneity and anisotropy increased the level of variability in the moderate-to-high strains decreased while the level of variability in the moderate-to-high stresses increased. However, this is not the pattern observed when CVs calculated from empirical data were applied to the material properties where the lowest level of variability in both stresses and strains occurred when the cranium was modeled with a low level of non-homogeneity and anisotropy. Therefore, when constant material property variability is assumed, inaccurate trends in the level of variability present in modest-to-high magnitude stresses and strains are produced. When the cranium is modeled with the highest level of accuracy (high non-homogeneity and anisotropy) and when randomness in the material properties is calculated from empirical data, there is a large level of variability in the significant strains (CV=0.369) and a low level of variability in the modest-to-high magnitude stresses (CV=0.150). This result may have important implications with regard to the mechanical signals driving bone remodeling and adaptation through natural selection. PMID- 22306514 TI - Aggregate reactivation mediated by the Hsp100 chaperones. AB - Hsp100 family of molecular chaperones shows a unique capability to resolubilize and reactivate aggregated proteins. The Hsp100-mediated protein disaggregation is linked to the activity of other chaperones from the Hsp70 and Hsp40 families. The best-studied members of the Hsp100 family are the bacterial ClpB and Hsp104 from yeast. Hsp100 chaperones are members of a large super-family of energy-driven conformational "machines" known as AAA+ ATPases. This review describes the current mechanistic model of the chaperone-induced protein disaggregation and explains how the structural architecture of Hsp100 supports disaggregation and how the co-chaperones may participate in the Hsp100-mediated reactions. PMID- 22306516 TI - Multiple biological functions of sporamin related to stress tolerance in sweet potato (Ipomoea batatas Lam). AB - The initial investigation of the nature of the proteins in the tuber of sweet potato (Ipomoea batatas Lam.) revealed a globulin-designated "ipomoein," which was reported by Jones and Gersdorff, (1931). Later, "ipomoein" was renamed "sporamin" and was found to be a major storage protein that accounted for over 80% of the total protein in the tuberous root. To date, sporamin has been studied by a series of biochemical and molecular approaches. The first purification of sporamin into two major fractions, A and B, was successfully completed in 1985. Several characteristics of the protein, such as the diversification of the nucleotide sequences in the gene family, the protein structure, the biological functions of storage, defense, inhibitory activity and ROS scavenging, were identified. In the past decade, sporamin was classified as a Kunitz-type trypsin inhibitor, and its insect-resistance capability has been examined in transgenic tobacco and cauliflower plants, indicating the multiple functions of this protein has evolved to facilitate the growth and development of sweet potato. Sporamin is constitutively expressed in the tuberous root and is not normally expressed in the stem or leaves. However, this protein is expressed systemically in response to wounding and other abiotic stresses. These dual expression patterns at the transcriptional level revealed that the complex regulatory mechanism of sporamin was modulated by environmental stresses. The versatile functions of sporamin make this storage protein a good research model to study molecular evolution, regulatory mechanisms and physiological functions in plants. This review summarizes and discusses recent approaches and future perspectives in agricultural biotechnology. PMID- 22306517 TI - Rosmarinic acid as a protective agent against genotoxicity of ethanol in mice. AB - The aim of the present work was to study the protective effects of rosmarinic acid against ethanol-induced DNA damage in mice. The antigenotoxic capacity of rosmarinic acid (100 mg/kg) was tested using pre-, co- and post-treatment with ethanol (5 g/kg). Peripheral blood (1 and 24 h) and brain cells (24 h) were evaluated using the comet assay and bone marrow was analyzed using the micronucleus assay (24 h). The results were compared to data of TBARS, enzymes with antioxidant activity, and DCFH-DA test. Peripheral blood and brain cells show that mean damage index (DI) and damage frequency (DF) values of ethanol with pre-treatment with rosmarinic acid group were significantly lower than in the ethanol group. In brain cells all different treatments with ethanol and rosmarinic acid showed significant decrease in DI and DF mean values when compared to ethanol group and negative control. No significant differences were observed in micronucleus frequency, activity of antioxidant enzymes and TBARS between groups. The DCFH-DA test show a reduction of 18% of fluorescence intensity when compare with ethanol group. The results show that rosmarinic acid could decrease the levels of DNA damage induced by ethanol, for both tissues and treatment periods. PMID- 22306515 TI - Unconventional functions of microtubule motors. AB - With the functional characterization of proteins advancing at fast pace, the notion that one protein performs different functions - often with no relation to each other - emerges as a novel principle of how cells work. Molecular motors are no exception to this new development. Here, we provide an account on recent findings revealing that microtubule motors are multifunctional proteins that regulate many cellular processes, in addition to their main function in transport. Some of these functions rely on their motor activity, but others are independent of it. Of the first category, we focus on the role of microtubule motors in organelle biogenesis, and in the remodeling of the cytoskeleton, especially through the regulation of microtubule dynamics. Of the second category, we discuss the function of microtubule motors as static anchors of the cargo at the destination, and their participation in regulating signaling cascades by modulating interactions between signaling proteins, including transcription factors. We also review atypical forms of transport, such as the cytoplasmic streaming in the oocyte, and the movement of cargo by microtubule fluctuations. Our goal is to provide an overview of these unexpected functions of microtubule motors, and to incite future research in this expanding field. PMID- 22306518 TI - The Premotor theory of attention: time to move on? AB - Spatial attention and eye-movements are tightly coupled, but the precise nature of this coupling is controversial. The influential but controversial Premotor theory of attention makes four specific predictions about the relationship between motor preparation and spatial attention. Firstly, spatial attention and motor preparation use the same neural substrates. Secondly, spatial attention is functionally equivalent to planning goal directed actions such as eye-movements (i.e. planning an action is both necessary and sufficient for a shift of spatial attention). Thirdly, planning a goal directed action with any effector system is sufficient to trigger a shift of spatial attention. Fourthly, the eye-movement system has a privileged role in orienting visual spatial attention. This article reviews empirical studies that have tested these predictions. Contrary to predictions one and two there is evidence of anatomical and functional dissociations between endogenous spatial attention and motor preparation. However, there is compelling evidence that exogenous attention is reliant on activation of the oculomotor system. With respect to the third prediction, there is correlational evidence that spatial attention is directed to the endpoint of goal-directed actions but no direct evidence that this attention shift is dependent on motor preparation. The few studies to have directly tested the fourth prediction have produced conflicting results, so the extent to which the oculomotor system has a privileged role in spatial attention remains unclear. Overall, the evidence is not consistent with the view that spatial attention is functionally equivalent to motor preparation so the Premotor theory should be rejected, although a limited version of the Premotor theory in which only exogenous attention is dependent on motor preparation may still be tenable. A plausible alternative account is that activity in the motor system contributes to biased competition between different sensory representations with the winner of the competition becoming the attended item. PMID- 22306519 TI - Prisms and neglect: what have we learned? AB - Since Rossetti et al. (1998) reported that prism adaptation (PA) can lead to a substantial reduction of neglect symptoms PA has become a hot topic in neglect research. More than 280 articles have been published in this area. Not all of those studies investigated the therapeutic potential of this technique, many studies examined the responsiveness to PA as a way to subdivide neglect into separate subsyndromes, other studies focussed on the process of PA itself in an effort to illuminate its underlying neurobiological mechanisms. In this article we will review research in all of these three areas to determine whether and to what extent research on PA in neglect patients has fulfilled its promise as a new way to improve the treatment of neglect, enhance our understanding of this complex syndrome and provide new insights into the neurobiology of sensorimotor learning. PMID- 22306520 TI - Rehabilitation of neglect: an update. AB - Spatial neglect is a characteristic sign of damage to the right hemisphere and is typically characterized by a failure to respond to stimuli on the left side. With about a third of stroke victims showing initial signs of neglect, it is a frequent but also one of the most disabling neurological syndromes. Despite partial recovery in the first months after stroke one third of these patients remain severely disabled in all daily activities, have a poor rehabilitation outcome and therefore require specific treatment. The last decades have seen an intensive search for novel, more effective treatments for this debilitating disorder. An impressive range of techniques to treat neglect has been developed in recent years. Here, we describe those techniques, review their efficacy and identify gaps in the current research on neglect therapy. PMID- 22306521 TI - Similar spatial patterns of neural coding of category selectivity in FFA and VWFA under different attention conditions. AB - It has long been debated whether attention alters the categorical selectivity in regions such as the fusiform face area (FFA) and the visual word form area (VWFA). We addressed this issue by examining whether the spatial pattern of neural representations for certain stimulus categories in these regions would change under different attention conditions. Faces, Chinese characters, and textures were presented in a block design fMRI experiment where participants in different runs attended to the stimuli under different conditions of attention. After localizing regions of interest (ROIs) in FFA and VWFA using general linear models, we performed spatial pattern analyses to examine both within- and cross condition classification in these ROIs. The within-condition results replicated previous findings showing significant classification accuracy reduction when there was less attention compared with more attention. Critically, cross condition classification in both FFA and VWFA revealed significantly above-chance accuracy for all stimulus categories, suggesting similar spatial neural representations across different attention conditions. Further strengthening this conclusion, when the contrast-to-noise ratio (CNR) of the signals was adjusted to increase signal strength, cross-condition classification accuracy for faces in FFA and for Chinese characters in VWFA improved significantly, even approaching within-condition accuracy. This indicates that attention does not modulate the spatial pattern of neural representations involved in category selectivity, but only changes the signal strength relative to the noise level. PMID- 22306522 TI - Light-driven chemical synthesis. AB - Depletion of the fossil fuel reserves of the Earth has prompted research into sources of renewable and sustainable energy, and feedstock for the chemical and pharmaceutical industries to support the transition towards a bio-based society. Photosynthesis efficiently captures solar energy, but its subsequent conversion into chemical energy in the form of biomass is limited to a final output in the 1 4% range. Re-routing of photosynthetic electron transport and reducing power directly into desired biosynthetic pathways offers a new avenue for sustainable production of high-value products. PMID- 22306523 TI - Formulation, pharmacokinetics and pharmacodynamics of topical microbicides. AB - The development of safe topical microbicides that effectively prevent human immunodeficiency virus (HIV) infection is a major goal in curbing the human immunodeficiency virus pandemic. A number of past failures resulting from mucosal toxicity or lack of efficacy have informed the field. Products that caused toxicity to the female genital tract mucosa, and thereby increased the likelihood of HIV acquisition, included nonoxynol 9, cellulose sulfate, and C31 G vaginal gel Savvy. Topical products that were ineffective in preventing HIV infection include BufferGel, Carraguard, and PRO 2000. Antiretroviral drugs such as tenofovir and dapivirine formulated into microbicide products have shown promise, but there is much to learn about ideal product formulation and acceptability, and drug distribution and disposition (pharmacokinetics). Current formulations for water-soluble molecules include vaginally or rectally applied gels, vaginal rings, films and tablets. Dosing strategies (e.g. coitally dependent or independent) will be based on the pharmacokinetics of the active ingredient and the tolerance for less than perfect adherence. PMID- 22306525 TI - Methamphetamine-induced dopamine terminal deficits in the nucleus accumbens are exacerbated by reward-associated cues and attenuated by CB1 receptor antagonism. AB - Methamphetamine (METH) exposure is primarily associated with deleterious effects to dopaminergic neurons. While several studies have implicated the endocannabinoid system in METH's locomotor, rewarding and neurochemical effects, a role for this signaling system in METH's effects on dopamine terminal dynamics has not been elucidated. Given that CB1 receptor blockade reduces the acute potentiation of phasic extracellular dopamine release from other psychomotor stimulant drugs and that the degree of acute METH-induced increases in extracellular dopamine levels is related to the severity of dopamine depletion, we predicted that pretreatment with the CB1 receptor antagonist rimonabant would reduce METH-induced alterations at dopamine terminals. Furthermore, we hypothesized that administration of METH in environments where reward associated cues were present would potentiate METH's acute effects on dopamine release in the nucleus accumbens and exacerbate changes in dopamine terminal activity. Fast scan cyclic voltammetry was used to measure electrically-evoked dopamine release in the nucleus accumbens and revealed markers of compromised dopamine terminal integrity nine days after a single dose of METH. These were exacerbated in animals that received METH in the presence of reward-associated cues, and attenuated in rimonabant-pretreated animals. While these deficits in dopamine dynamics were associated with reduced operant responding on days following METH administration in animals treated with only METH, rimonabant-pretreated animals exhibited levels of operant responding comparable to control. Moreover, dopamine release correlated significantly with changes in lever pressing behavior that occurred on days following METH administration. Together these data suggest that the endocannabinoid system is involved in the subsecond dopaminergic response to METH. PMID- 22306526 TI - Estrogen receptor alpha overexpressing mouse antral follicles are sensitive to atresia induced by methoxychlor and its metabolites. AB - Methoxychlor (MXC) and its metabolites bind to estrogen receptors (ESRs) and increase ovarian atresia. To test whether ESR alpha (ESR1) overexpressing (ESR1 OE) antral follicles are more sensitive to atresia compared to controls, we cultured antral follicles with vehicle, MXC (1-100 MUg/ml) or metabolites (0.1-10 MUg/ml). Results indicate that MXC and its metabolites significantly increase atresia in ESR1 OE antral follicles at lower doses compared to controls. Activity of pro-apoptotic factor caspase-3/7 was significantly higher in ESR1 OE treated antral follicles compared to controls. ESR1 OE mice dosed with MXC 64 mg/kg/day had an increased percentage of atretic antral follicles compared to controls. Furthermore, pro-caspase-3 levels were found to be significantly lower in ESR1 OE ovaries than controls dosed with MXC 64 mg/kg/day. These data suggest that ESR1 OE ovaries are more sensitive to atresia induced by MXC and its metabolites in vitro and in vivo compared to controls. PMID- 22306527 TI - Quantitative structure-activity relationship analysis of perfluoroiso propyldinitrobenzene derivatives known as photosystem II electron transfer inhibitors. AB - Quantitative structure-activity relationship (QSAR) analysis of the twenty-six perfluoroisopropyl-dinitrobenzene (PFIPDNB) derivatives was performed to explain their ability to suppress photochemical activity of the plants photosystem II using chloroplasts and subchloroplast thylakoid membranes enriched in photosystem II, called DT-20. Compounds were optimized by semi-empirical PM3 and DFT/B3LYP/6 31G methods. The Heuristic and the Best Multi-Linear Regression (BMLR) method in CODESSA were used to select the most appropriate molecular descriptors and to develop a linear QSAR model between experimental pI(50) values and the most significant set of the descriptors. The obtained models were validated by cross validation (R(2)(cv)) and internal validation to confirm the stability and good predictive ability. The obtained eight models with five-parameter show that: (a) coefficient (R(2)) value of the chloroplast samples are slightly higher than that of the DT-20 samples both of Heuristic and BMLR models; (b) the coefficients of the BMLR models are slightly higher than that of Heuristic models both of chloroplasts and DT-20 samples; (c) The YZ shadow parameter and the indicator parameter, for presence of NO(2) substituent in the ring, are the most important descriptor at PM3-based and DFT-based QSAR models, respectively. This article is part of a Special Issue entitled: Photosynthesis Research for Sustainability: from Natural to Artificial. PMID- 22306524 TI - Neuroglialpharmacology: myelination as a shared mechanism of action of psychotropic treatments. AB - Current psychiatric diagnostic schema segregate symptom clusters into discrete entities, however, large proportions of patients suffer from comorbid conditions that fit neither diagnostic nor therapeutic schema. Similarly, psychotropic treatments ranging from lithium and antipsychotics to serotonin reuptake inhibitors (SSRIs) and acetylcholinesterase inhibitors have been shown to be efficacious in a wide spectrum of psychiatric disorders ranging from autism, schizophrenia (SZ), depression, and bipolar disorder (BD) to Alzheimer's disease (AD). This apparent lack of specificity suggests that psychiatric symptoms as well as treatments may share aspects of pathophysiology and mechanisms of action that defy current symptom-based diagnostic and neuron-based therapeutic schema. A myelin-centered model of human brain function can help integrate these incongruities and provide novel insights into disease etiologies and treatment mechanisms. Available data are integrated herein to suggest that widely used psychotropic treatments ranging from antipsychotics and antidepressants to lithium and electroconvulsive therapy share complex signaling pathways such as Akt and glycogen synthase kinase-3 (GSK3) that affect myelination, its plasticity, and repair. These signaling pathways respond to neurotransmitters, neurotrophins, hormones, and nutrition, underlie intricate neuroglial communications, and may substantially contribute to the mechanisms of action and wide spectra of efficacy of current therapeutics by promoting myelination. Imaging and genetic technologies make it possible to safely and non-invasively test these hypotheses directly in humans and can help guide clinical trial efforts designed to correct myelination abnormalities. Such efforts may provide insights into novel avenues for treatment and prevention of some of the most prevalent and devastating human diseases. PMID- 22306528 TI - The PsbQ protein stabilizes the functional binding of the PsbP protein to photosystem II in higher plants. AB - PsbP and PsbQ proteins are extrinsic subunits of photosystem II (PSII) and optimize the oxygen evolution reaction by regulating the binding properties of the essential cofactors Ca(2+) and Cl(-). PsbP induces conformational changes around the catalytic Mn cluster required for Ca(2+) and Cl(-) retention, and the N-terminal region of PsbP is essential for this reaction. It was reported that PsbQ partially restores the functional defect of N-terminal truncated PsbP [Ifuku and Sato (2002) Plant Cell Physiol. 43, 1244-1249]; however, the mechanism of this restoration is yet to be clarified. In this study, we demonstrate that PsbQ is able to restore the functional binding of mutated PsbPs. In the presence of PsbQ, ?15-PsbP, a truncated PsbP lacking 15 N-terminal residues, was able to specifically bind to NaCl-washed spinach PSII membranes and significantly restore the oxygen evolving activity. Furthermore, PsbQ was also able to compensate for the impaired ion-retention of H144A-PsbP, in which a conserved histidine at position 144 in the C-terminal domain was substituted with an alanine. Fourier transform infrared (FTIR) difference spectroscopy showed that PsbQ restored the ability of ?15- and H144A-PsbP to induce proper conformational changes during S(1) to S(2) transition. These data suggest that the major function of PsbQ is to stabilize PsbP binding, thereby contributing to the maintenance of the catalytic Mn cluster of the water oxidation machinery in higher plant PSII. This article is part of a Special Issue entitled: Photosynthesis Research for Sustainability: from Natural to Artificial. PMID- 22306529 TI - Small-angle neutron scattering study of the ultrastructure of chloroplast thylakoid membranes - periodicity and structural flexibility of the stroma lamellae. AB - The multilamellar organization of freshly isolated spinach and pea chloroplast thylakoid membranes was studied using small-angle neutron scattering. A broad peak at ~0.02A(-1) is ascribed to diffraction from domains of ordered, unappressed stroma lamellae, revealing a repeat distance of 294A+/-7A in spinach and 345A+/-11A in pea. The peak position and hence the repeat distance of stroma lamellae is strongly dependent on the osmolarity and the ionic strength of the suspension medium, as demonstrated by varying the sorbitol and the Mg(++) concentration in the sample. For pea thylakoid membranes, we show that the repeat distance decreases when illuminating the sample with white light, in accordance with our earlier results on spinach, also regarding the observation that addition of an uncoupler prohibits the light-induced structural changes, a strong indication that these changes are driven by the transmembrane proton gradient. We show that the magnitude of the shrinkage is strongly dependent on light intensity and that the repeat distance characteristic of the dark state after illumination is different from the initial dark state. Prolonged strong illumination leads to irreversible changes and swelling as reflected in increased repeat distances. The observed reorganizations are discussed within the frames of the current structural models of the granum-stroma thylakoid membrane assembly and the regulatory mechanisms in response to variations in the environmental conditions in vivo. This article is part of a Special Issue entitled: Photosynthesis Research for Sustainability: from Natural to Artificial. PMID- 22306530 TI - Chronic air pollution exposure during pregnancy and maternal and fetal C-reactive protein levels: the Generation R Study. AB - BACKGROUND: Exposure to air pollution has been associated with higher C-reactive protein (CRP) levels, suggesting an inflammatory response. Not much is known about this association in pregnancy. OBJECTIVES: We investigated the associations of air pollution exposure during pregnancy with maternal and fetal CRP levels in a population-based cohort study in the Netherlands. METHODS: Particulate matter (PM) with an aerodynamic diameter <= 10 MUm (PM10) and nitrogen dioxide (NO2) levels were estimated at the home address using dispersion modeling for different averaging periods preceding the blood sampling (1 week, 2 weeks, 4 weeks, and total pregnancy). High-sensitivity CRP levels were measured in maternal blood samples in early pregnancy (n = 5,067) and in fetal cord blood samples at birth (n = 4,450). RESULTS: Compared with the lowest quartile, higher PM10 exposure levels for the prior 1 and 2 weeks were associated with elevated maternal CRP levels (> 8 mg/L) in the first trimester [fourth PM10 quartile for the prior week: odds ratio (OR), 1.32; 95% confidence interval (CI): 1.08, 1.61; third PM10 quartile for the prior 2 weeks: OR, 1.28; 95% CI: 1.06, 1.56]; however, no clear dose-response relationships were observed. PM10 and NO2 exposure levels for 1, 2, and 4 weeks preceding delivery were not consistently associated with fetal CRP levels at delivery. Higher long-term PM10 and NO2 exposure levels (total pregnancy) were associated with elevated fetal CRP levels (> 1 mg/L) at delivery (fourth quartile PM10: OR, 2.18; 95% CI: 1.08, 4.38; fourth quartile NO2: OR, 3.42; 95% CI: 1.36, 8.58; p-values for trend < 0.05). CONCLUSIONS: Our results suggest that exposure to air pollution during pregnancy may lead to maternal and fetal inflammatory responses. PMID- 22306531 TI - Bond strengths, degree of conversion of the cement and molecular structure of the adhesive-dentine joint in fibre post restorations. AB - OBJECTIVES: Because fibre post restorations are influenced by multiple factors such as the types of bonding materials, the dentine region and the time under moist exposure, this study sought to determine the bond strength of endodontic restorations and its relation to the degree of conversion of the cement layer and the molecular structure of the dentine-bonded joints. METHODS: The performance of 2 etch-and-rinse (All-Bond 2 and One-Step Plus) and 2 self-etch (Clearfil SE Bond and Xeno III) adhesives at post spaces regions, after 7 d or 4 m, was evaluated. FRC Postec Plus posts were cemented to the root canal with a dual-cure resin cement (Duo-Link). Transverse sections of the tooth were subjected to push-out testing, to degree-of-conversion measurements and to hybrid layer evaluation through MU-Raman spectroscopy. RESULTS: Coronal bonding was higher than cervical and middle bonding. The hybrid layer was thicker for the etch-and-rinse systems, with thicknesses decreasing towards the middle region. The degree of conversion measured for the 3-step etch-and-rinse group after 4 m was significantly higher than that for the self-etching groups. CONCLUSIONS: Although not totally stable at the adhesive-dentine interface, the 3-step etch-and-rinse adhesive in the coronal dentine provided the best bond strength, degree of conversion of the cement and hybrid layer thickness in post restorations, in both short- and long term analyses. PMID- 22306532 TI - Evaluation of self shade matching ability of dental students using visual and instrumental means. AB - OBJECTIVES: The purpose of this study was to evaluate the ability of dental students to match the shade of their own teeth. METHODS: Fifty female dental students in the College of Dentistry at King Saud University, who had not received any formal dental training in color science or shade matching procedures, were screened for color deficiencies and selected to participate in the study. Each subject and three clinicians selected independently the closest match for the subjects' own right or left sound maxillary central incisors under controlled viewing conditions, using VITA classical shade guide (VITA Zahnfabrik GmbH, Bad Sackingen, Germany). Each examined central incisor and the 16 samples of VITA classical shade guide were measured with the VITA Easy Shade (VES) spectrophotometer to determine the CIELAB color parameters. The color differences (DeltaE) between each examined tooth and the 16 samples of the shade guide were calculated. The minimum DeltaE values were compared to DeltaE values of the shade obtained by VES, subjects and clinicians. RESULTS: The results showed a significant difference in the accuracy of shade selection between the instrumental and visual means. DeltaE value of shade selected by clinicians was significantly lower than those selected by the subjects. CONCLUSIONS: It was concluded that, spectrophotometric shade analysis was more accurate compared to human shade assessment. CLINICAL SIGNIFICANCE: A reliable self-perception of the subjects' own tooth color, may aid in the shade matching procedures. It might lead to increased patients' satisfaction at the finalization of the restorative procedures. PMID- 22306533 TI - Shape-based assessment of vertebral fracture risk in postmenopausal women using discriminative shape alignment. AB - RATIONALE AND OBJECTIVES: Risk assessment of future osteoporotic vertebral fractures is currently based mainly on risk factors, such as bone mineral density, age, prior fragility fractures, and smoking. It can be argued that an osteoporotic vertebral fracture is not exclusively an abrupt event but the result of a decaying process. To evaluate fracture risk, a shape-based classifier, identifying possible small prefracture deformities, may be constructed. MATERIALS AND METHODS: During a longitudinal case-control study, a large population of postmenopausal women, fracture free at baseline, were followed. The 22 women who sustained at least one lumbar fracture on follow-up represented the case group. The control group comprised 91 women who maintained skeletal integrity and matched the case group according to the standard osteoporosis risk factors. On radiographs, a radiologist and two technicians independently performed manual annotations of the vertebrae, and fracture prediction using shape features extracted from the baseline annotations was performed. This was implemented using posterior probabilities from a standard linear classifier. RESULTS: The classifier tested on the study population quantified vertebral fracture risk, giving statistically significant results for the radiologist annotations (area under the curve, 0.71 +/- 0.013; odds ratio, 4.9; 95% confidence interval, 2.94 8.05). CONCLUSIONS: The shape-based classifier provided meaningful information for the prediction of vertebral fractures. The approach was tested on case and control groups matched for osteoporosis risk factors. Therefore, the method can be considered an additional biomarker, which combined with traditional risk factors can improve population selection (eg, in clinical trials), identifying patients with high fracture risk. PMID- 22306534 TI - Testing the cumulative stress and mismatch hypotheses of psychopathology in a rat model of early-life adversity. AB - BACKGROUND: In the present study, we tested both the cumulative stress and the mismatch hypothesis of psychopathology. For this purpose the combined effects of early-life adversity and later-life stress exposure on behavioral markers of psychosis susceptibility were studied in male Wistar rats. METHOD: Experiment I: rat pups divided on the basis of the levels of their maternal care experience in low, medium or high maternal care groups, were reared post-weaning in groups (Exp. IA) or in social isolation (Exp. IB) and tested at adulthood under basal conditions or after an acute corticosterone (CORT) administration. Maternal care levels were assessed by measuring the dam's licking and grooming (LG) the first postnatal week of life. Experiment II: rat pups exposed as neonates to daily sessions of 8h of maternal separation (MS) on postnatal days 3, 4 and 5 either altogether in their home cage (HOME SEP) or alone in a novel environment (NOVEL SEP), were reared post-weaning in groups and tested at adulthood under basal conditions. Adult testing included behaviors marking psychosis susceptibility: apomorphine-induced gnawing (APO-gnawing), acoustic startle response and its modulation by a prepulse stimulus (PPI). The behavior of the Medium LG offspring was used as baseline reference for all the three experiments. RESULTS: Experiment I: Low maternal LG history alone had limited effects on the behavior of Wistar offspring, although increased acoustic startle and increased PPI, at high prepulse intensity levels, were observed. When low maternal LG history was combined with post-weaning social isolation, basal APO-gnawing was decreased and PPI increased, compared to High LG and Med LG offspring. This reflects attenuated psychosis susceptibility. High LG offspring reared in isolation displayed, however, the highest APO-gnawing and the lowest PPI levels among rats reared in social isolation, which is indicative for increased psychosis susceptibility. These findings support the mismatch hypothesis. For demonstration of the cumulative stress hypothesis an injection of CORT in the adult Low LG offspring was required that increased APO-gnawing and reduced PPI. This CORT-induced PPI disruption was greatly enhanced after additional isolation rearing. The High LG group, either socially housed or reared in isolation, was resistant to the acute effects of CORT at adulthood. Experiment II: MS increased psychosis susceptibility only in NOVEL SEP rats that had experienced MS in the context of early social isolation. These individuals displayed increased adult APO-gnawing and reduced PPI, if reared post-weaning in a condition that does not match with their early life social environment (i.e. group housing). This finding supports the mismatch hypothesis. CONCLUSION: The outcome of environmental manipulations on developmental programming of psychosis susceptibility depends on the interplay of early-life adversity and later-life stressors in a manner that supports the mismatch hypothesis. However, evidence for the cumulative stress hypothesis arises if vulnerable individuals are exposed in later life additionally to excess of the stress hormone CORT. PMID- 22306535 TI - Adiponectin, leptin, and yoga practice. AB - To address the mechanisms underlying hatha yoga's potential stress-reduction benefits, we compared adiponectin and leptin data from well-matched novice and expert yoga practitioners. These adipocytokines have counter-regulatory functions in inflammation; leptin plays a proinflammatory role, while adiponectin has anti inflammatory properties. Fifty healthy women (mean age=41.32, range=30-65), 25 novices and 25 experts, provided fasting blood samples during three separate visits. Leptin was 36% higher among novices compared to experts, P=.008. Analysis of adiponectin revealed a borderline effect of yoga expertise, P=.08; experts' average adiponectin levels were 28% higher than novices across the three visits. In contrast, experts' average adiponectin to leptin ratio was nearly twice that of novices, P=.009. Frequency of self-reported yoga practice showed significant negative relationships with leptin; more weeks of yoga practice over the last year, more lifetime yoga sessions, and more years of yoga practice were all significantly associated with lower leptin, with similar findings for the adiponectin to leptin ratio. Novices and experts did not show even marginal differences on behavioral and physiological dimensions that might represent potential confounds, including BMI, central adiposity, cardiorespiratory fitness, and diet. Prospective studies addressing increased risk for type II diabetes, hypertension, and cardiovascular disease have highlighted the importance of these adipocytokines in modulating inflammation. Although these health risks are clearly related to more extreme values then we found in our healthy sample, our data raise the possibility that longer-term and/or more intensive yoga practice could have beneficial health consequences by altering leptin and adiponectin production. PMID- 22306536 TI - Aspirin suppresses cardiac fibroblast proliferation and collagen formation through downregulation of angiotensin type 1 receptor transcription. AB - Aspirin (acetyl salicylic acid, ASA) is a common drug used for its analgesic and antipyretic effects. Recent studies show that ASA not only blocks cyclooxygenase, but also inhibits NADPH oxidase and resultant reactive oxygen species (ROS) generation, a pathway that underlies pathogenesis of several ailments, including hypertension and tissue remodeling after injury. In these disease states, angiotensin II (Ang II) activates NADPH oxidase via its type 1 receptor (AT1R) and leads to fibroblast growth and collagen synthesis. In this study, we examined if ASA would inhibit NADPH oxidase activation, upregulation of AT1R transcription, and subsequent collagen generation in mouse cardiac fibroblasts challenged with Ang II. Mouse heart fibroblasts were isolated and treated with Ang II with or without ASA. As expected, Ang II induced AT1R expression, and stimulated cardiac fibroblast growth and collagen synthesis. The AT1R blocker losartan attenuated these effects of Ang II. Similarly to losartan, ASA, and its SA moiety suppressed Ang II-mediated AT1R transcription and fibroblast proliferation as well as expression of collagens and MMPs. ASA also suppressed the expression of NADPH oxidase subunits (p22(phox), p47(phox), p67(phox), NOX2 and NOX4) and ROS generation. ASA did not affect total NF-kappaB p65, but inhibited its phosphorylation and activation. These observations suggest that ASA inhibits Ang II-induced NADPH oxidase expression, NF-kappaB activation and AT1R transcription in cardiac fibroblasts, and fibroblast proliferation and collagen expression. The critical role of NADPH oxidase activity in stimulation of AT1R transcription became apparent in experiments where ASA also inhibited AT1R transcription in cardiac fibroblasts challenged with H2O2. Since SA had similar effect as ASA on AT1R expression, we suggest that ASA's effect is mediated by its SA moiety. PMID- 22306537 TI - [Consensus for the management of IPMN]. PMID- 22306538 TI - [Histological subclassification of the pancreatic intraductal neoplasms]. PMID- 22306539 TI - [Carcinogenesis of IPMN]. PMID- 22306540 TI - [Clinical follow-up of branch duct IPMN]. PMID- 22306541 TI - [Endoscopic approach to IPMN]. PMID- 22306542 TI - [Diagnosis of liver diseases by classification of laboratory signal factor pattern findings with the Mahalanobis.Taguchi Adjoint method]. AB - There are many autoimmune liver diseases in which diagnosis is difficult so that overlap is accepted, and this negatively affects treatment. The initial diagnosis is therefore important for later treatment and convalescence. We distinguished autoimmune cholangitis, autoimmune hepatitis and primary biliary cirrhosis by the Mahalanobis.Taguchi Adjoint (MTA) method in the Mahalanobis.Taguchi system and analyzed the pattern of factor effects by the MTA method. As a result, the characteristic factor effect pattern of each disease was classified, enabling the qualitative evaluation of cases including overlapping cases which were difficult to diagnose. PMID- 22306543 TI - [A retrospective endoscopic case of adenoid cystic carcinoma of the esophagus]. AB - We report a case of a 64-year-old Japanese man with adenoid cystic carcinoma. An elevated lesion covered by intact epithelium in the thoracic esophagus was found in September, 2007 and been followed. After dysphagia appeared follow-up endoscopy was performed in January, 2010, and morphological change into a protruding tumor was recognized. Since adenoid cystic carcinoma was detected by endoscopic biopsy, the patient underwent esophageal resection. The resected specimen showed a cribriform pattern and a certain amount of mucous substance which was positive for Alcian blue, within a solid nest. The tumor cells were positive for S-100 protein and negative for alphaSMA, so the tumor was diagnosed as an adenoid cystic carcinoma. PMID- 22306544 TI - [A case of sarcomatoid carcinoma (undifferentiated carcinoma, sarcomatoid type) of the duodenum]. AB - A 98-year-old woman with aspiration pneumonia caused by vomiting was admitted to our hospital. Abdominal computed tomography and ultrasonography showed common bile duct dilation and occlusion of the gastrointestinal tract due to a large tumor in the duodenum. Aspiration pneumonia and hepatic failure led to the patient's death. Pathological autopsy showed an 11 * 6 * 2.5-cm polypoid tumor originating from the descending part of the duodenum and involving the common bile duct. Histological examination of the tumor showed mainly spindle cells but also some adenocarcinoma cells. Tumor cells, including spindle cells, were strongly positive for cytokeratin 7; therefore, sarcomatoid carcinoma originating from the duodenum was diagnosed. To the best of our knowledge, only 5 cases of sarcomatoid carcinoma originating from the duodenum have been reported, and they often show polypoid growth. The possibility of sarcomatoid carcinoma should be considered if such findings are noted. PMID- 22306545 TI - [Two cases of thiopurine-induced acute pancreatitis in inflammatory bowel disease]. AB - Thiopurine drugs have been widely used in the treatment of inflammatory bowel disease. However, their use is limited by adverse effect that can lead to cessation of therapy. We report 2 cases of thiopurine-induced acute pancreatitis in patients with inflammatory bowel disease. Both patients complained of abdominal pain, showed elevated pancreatic enzymes, and swollen pancreases on computed tomography. The patients' signs and symptoms resolved uneventfully after withdrawal of the thiopurine drugs. Although the mechanism of thiopurine-induced pancreatitis remains unclear, close monitoring and early recognition of acute pancreatitis is important in the management of new thiopurine users. PMID- 22306546 TI - [A case of cholangiolocellular carcinoma combined with intrahepatic cholangiocarcinoma diagnosed after 4 years follow-up for hepatic hemangioma]. AB - We report a rare case which had been followed up for hepatic hemangioma and in whom was surgical resection revealed with cholangiolocellular carcinoma (CoCC) combined with intrahepatic cholangiocarcinoma (ICC). A 69-year-old man who was an HBV carrier had been regularly followed up with hepatic hemangioma from November, 2005. Because the arterial phase of dynamic CT scan exhibited an enhanced lesion in the dorsal portion of the hemangioma on November, 2009, the patient was admitted for intensive examination of the liver tumor. After surgical resection of the tumor, histological examination revealed small irregular tubules in the outer part and scattered small duct structures in the inner part of the tumor. In addition, immunohistochemical analysis demonstrated that cytokeratin (CK) 7, CK19 and epithelial membrane antigen (EMA) were all positive in the outer part, and EMA was only negative in the inner part of the tumor. From these findings, this case was diagnosed as CoCC combined with ICC. PMID- 22306547 TI - [A case of autoimmune hepatitis diagnosed after acute hepatitis B]. AB - We describe a case of autoimmune hepatitis diagnosed after acute hepatitis B. The patient was a 65-year-old man admitted because of markedly elevated transaminase level. Laboratory tests showed positive IgM-HBc antibody and a short prothorombin time. He was diagnosed as severe acute hepatitis B due to sexual transmission. He received lamivudine and steroid pulse therapy. Transaminase level increased again after steroid pulse therapy and liver atrophy progressed, so cyclosporine was induced. Liver biopsy was done because of prolonged liver function disorder. Biopsy specimens showed not only centrizonal inflammation but also interface hepatitis and bridging fibrosis, which were characteristic of autoimmune hepatitis. We diagnosed autoimmune hepatitis which became clinically evident after acute hepatitis B. Lamivudine was discontinued 7 months after diagnosis and he is now receiving 3mg prednisolone. PMID- 22306548 TI - [A case of hepatic artery aneurysm that had formed asymptomatically and penetrated into the duodenum]. AB - A 41-year-old man was admitted to our hospital with gastrointestinal bleeding. Esophagogastroduodenoscopy revealed a submucosal protrusion with erosion in the duodenal bulb which was thought to be the bleeding source. Dynamic CT scan, ultrasonography and angiography of the abdomen revealed a hepatic artery aneurysm and a dilated celiac artery that dissected from its origin. Although we considered percutaneous transcatheter arterial embolization with metallic coils, we chose surgical resection and vascular reconstruction to prevent hepatic ischemia resulting from interruption of collateral circulation. On the 8(th) day, hepatic artery aneurysmectomy and revascularization with a great saphenous vein was carried out without any severe complication. The pathological specimen demonstrated segmental arterial mediolysis. PMID- 22306549 TI - [Osteoclast-like giant cell tumor (OGCT) of the liver: report of a case]. AB - A 57-year-old man presented with jaundice. Abdominal computed tomography showed a 10-cm left hepatic lobe heterogeneous solid mass with low attenuated areas in the mass, multiple liver metastases and lung metastasis. Serology for hepatitis B and C were negative. Serum alpha-fetoprotein, CEA and CA19-9 were normal. The patient died a few weeks later of progressive liver failure and an autopsy was performed. Histologically, the tumor consisted of sarcomatoid mononuclear cells and osteoclast-like giant cells. The liver tissue surrounding the tumor showed no cirrhotic pattern. The osteoclast-like giant cells were uniformly and strongly immunoreactive with CD68. The mononuclear cells demonstrated expression of vimentin but were negative for CAM5.2. The MIB-1 index was 20% for the mononuclear cells. In conclusion, the histopathological diagnosis revealed an osteoclast-like giant cell tumor of the liver. PMID- 22306550 TI - Expression of retinoid X receptor beta is induced in astrocytes during corpus callosum demyelination. AB - The experimental activation of retinoid receptors reduces pathological symptoms in animal models of multiple sclerosis. In order to assess the involvement of endogenous retinoid signaling during the process of demyelination we investigated retinoic acid synthesizing enzymes and nuclear receptors using the mouse model of cuprizone toxicity. The initiation of myelin degradation in the corpus callosum was accompanied with a local increase of retinaldehyde dehydrogenase (RALDH) immunoreactivity. On the level of receptors we observed a striking increase in protein expression of the retinoid X receptor (RXR)-beta in the affected corpus callosum. The RXRbeta immunoreactivity appeared exclusively in astrocytes, where it reached a maximum at five weeks of treatment, following the RALDH response. In the cerebral cortex and basal ganglia of affected mice RXRbeta was also observed in neurons. Among nuclear receptor antigens RARalpha showed a cuprizone associated increase in the corpus callosum. Quantitative RT-PCR revealed strong basal expression of RXRbeta and a significant, over 20-fold upregulation of the peroxisome proliferator-activated receptor-gamma during demyelination. The results indicate that compensatory mechanisms during central demyelination may engage nuclear receptor dimers with an RXRbeta partner. PMID- 22306551 TI - Lesson from the farm environment. AB - PURPOSE OF REVIEW: Several population-based studies have replicated the finding that exposure to a farm environment is protective against the development of atopic diseases. From these studies, novel insights into potential allergy protective mechanisms were retrieved. This review focuses on consistent and novel findings of immune mechanisms involved in the 'farm effect'. RECENT FINDINGS: The most recent studies suggest that the 'farm effect' mediated by microbial exposure may be attributed to both microbial diversity and species specificity. There is convincing evidence that farm milk components and grass arabinogalactan, commonly found in cowshed, may be important. Furthermore, early exposure to a farming environment, in particular in utero, showed stronger effects than exposure later in life, potentially through modulation of the immature immune system by microbes, also involving epigenetic changes. This protective 'farm effect' remains in later adulthood. Regarding gene-environment interactions, polymorphisms in GRM1 interacted with farming in a genome-wide interaction scan for asthma. SUMMARY: The novel studies strengthen the role of microbial exposure and farm milk and grass components, especially early in life, in the modulation of the immune system towards a Th1/Treg predominance. This may subsequently lead to a long-lasting lower risk of developing atopic diseases. PMID- 22306552 TI - The role of lymphocyte proliferation tests in assessing occupational sensitization and disease. AB - PURPOSE OF REVIEW: Lymphocyte proliferation testing (LPT) is used in diagnosing occupationally acquired delayed-type hypersensitivity. It has been used in beryllium-health effects, and its role is expanding in metal allergy. It may find application in diagnosis of other sensitizers. RECENT FINDINGS: Use of the beryllium LPT (BeLPT) in medical surveillance identifies beryllium sensitization at low exposure with chronic beryllium disease (CBD) that leads to physiologic impairment and need for immunosuppressive medications. New studies indicate that both beryllium exposure and genetic variation are associated with increased risk of CBD. Borderline positive BeLPTs warrant inclusion into diagnostic algorithms. Furthermore, use of LPTs to diagnose metal allergy is being proposed in diagnosis of chromium allergy and hypersensitivity to surgical implants. New occupational sensitizers continue to be identified including metalworking fluids, the sterilizing agent ortho-phthalaldehyde and the solvent para chlorobenzotrifluoride. Use of LPT in occupational surveillance to these agents and other known sensitizers may play expanding roles. SUMMARY: Lymphocyte proliferation testing serves a valuable role in diagnosing occupational sensitization, as demonstrated with beryllium-health effects, as cases continue to be found at low exposure levels. The use of LPTs in diagnosing contact allergy is expanding, and new applications may be identified in human and animal studies. PMID- 22306553 TI - The effect of environmental oxidative stress on airway inflammation. AB - PURPOSE OF REVIEW: Asthma is an inflammatory respiratory condition with significantly associated morbidity and mortality that is increasing in prevalence. Air pollution is an important factor in both the development of asthma and in asthma exacerbations. Oxidative stress as a result of exposure to air pollution and underlying genetic polymorphisms that may play a role in susceptibility to this oxidative stress are the subject of current investigation. This article reviews the data regarding the effects of air pollution on the innate immune response and potential clinical and treatment implications of how genetic polymorphisms affect this response. RECENT FINDINGS: Recent investigation reveals how pollutant-induced oxidative stress impacts airway inflammatory responses. Work by our study group demonstrates that asthmatic patients have an exaggerated inflammatory response to air pollution-induced oxidative stress. New trials investigating antioxidants as potential therapeutic interventions may target this specific issue. SUMMARY: Air pollution plays a critical role in asthma and may affect certain patients more than others. Further investigation into the genetic polymorphisms that affect inflammatory responses may help target patient populations at greatest risk for air pollution-induced asthma and may provide new therapeutic options for these patient populations. PMID- 22306554 TI - Immunological and inflammatory responses to organic dust in agriculture. AB - PURPOSE OF REVIEW: Agriculture represents a major industry worldwide, and despite protection against the development of IgE-mediated diseases, chronic exposure to agriculture-related organic dusts is associated with an increased risk of developing respiratory disease. This article will review the literature regarding new knowledge of important etiologic agents in the dusts and focus on the immunologic responses following acute and repetitive organic dust exposures. RECENT FINDINGS: Although endotoxin remains important, there is an emerging role of nonendotoxin components such as peptidoglycans from Gram-positive bacteria. Pattern recognition receptors including Toll-like receptor 4 (TLR4), TLR2 and intracellular nucleotide oligomerization domain-like receptors are partially responsible for mediating the inflammatory consequences. Repeated organic dust exposures modulate innate and adaptive immune function with a resultant adaptation-like response. However, repetitive exposures cause lung parenchymal inflammation, chronic disease, and lung function decline over time. SUMMARY: The immunological consequences of organic dust exposure in the farming industry are likely explained by the diversity of microbial motifs in dust that can elicit differing innate immune receptor signaling pathways. Whereas initial activation results in a robust inflammatory response, repetitive dust exposures modulate immunity. This can result in low-grade, chronic inflammation, and/or protection against allergic disease. PMID- 22306555 TI - Epigenetics mediate environment : gene effects on occupational sensitization. AB - PURPOSE OF REVIEW: Epigenetics is the study of stable modifications of fixed genomes that direct which genes are expressed and which are silenced. Epigenetic changes are modulated by environmental exposures, making epigenetics the interface between genes and environment. This has particular relevance in understanding the effect of occupational exposures on the expression of allergic disease. The goal of this review is to describe how epigenetic changes affect transcription potential, and to examine more closely the effect of specific environmental and occupational exposures on epigenetic variations that alter allergy gene transcripts and the inflammatory milieu. RECENT FINDINGS: Gene transcription is activated when specific CpG sites are demethylated and histones are acetylated, and, conversely, silenced when sites are methylated and histones deacetylated. The development of Th1 and Th2 phenotypes, and expression of Treg cells, are now known to be modulated by epigenetic mechanisms. Workplace exposures such as tobacco smoke, particulates, diesel exhaust, polyaromatic hydrocarbons, ozone, and endotoxin, among others, suppress Treg development, and enhance expression of inflammatory cytokines and allergic phenotypes by epigenetic means. SUMMARY: Epigenetic manipulation to open and close transcription sites provides flexibility of gene expression in response to changing environmental cues. It may also be the window whereby allergic disease in the workplace can be reduced by targeted environmental interventions. PMID- 22306556 TI - Racial/ethnic differences in responses to the everyday discrimination scale: a differential item functioning analysis. AB - The authors examined the impact of race/ethnicity on responses to the Everyday Discrimination Scale, one of the most widely used discrimination scales in epidemiologic and public health research. Participants were 3,295 middle-aged US women (African-American, Caucasian, Chinese, Hispanic, and Japanese) from the Study of Women's Health Across the Nation (SWAN) baseline examination (1996 1997). Multiple-indicator, multiple-cause models were used to examine differential item functioning (DIF) on the Everyday Discrimination Scale by race/ethnicity. After adjustment for age, education, and language of interview, meaningful DIF was observed for 3 (out of 10) items: "receiving poorer service in restaurants or stores," "being treated as if you are dishonest," and "being treated with less courtesy than other people" (all P's < 0.001). Consequently, the "profile" of everyday discrimination differed slightly for women of different racial/ethnic groups, with certain "public" experiences appearing to have more salience for African-American and Chinese women and "dishonesty" having more salience for racial/ethnic minority women overall. "Courtesy" appeared to have more salience for Hispanic women only in comparison with African-American women. Findings suggest that the Everyday Discrimination Scale could potentially be used across racial/ethnic groups as originally intended. However, researchers should use caution with items that demonstrated DIF. PMID- 22306558 TI - Invited commentary: the action in the interaction and exposure modification. AB - The study of disease variability in populations is a goal of modern epidemiology. Because most common diseases arise out of a combination of factors and events (exposures, heritability, comorbidities, and chance), developing simple models of characterizing joint events is a daunting task. Dr. Weinberg argues successfully in this issue of the Journal (Am J Epidemiol. 2012;175(7):602-605) that additive null models can capture pure forms of independent causal effects in studies of rare conditions. Moreover, the concept of exposure modification, which characterizes most gene-environment interactions reported to date, is introduced. More cross-talk between biologists and epidemiologists is needed to tackle key issues in chronic disease etiology, and the argument for the use of parsimonious joint models in epidemiology is convincing. PMID- 22306557 TI - A causal framework for understanding the effect of losses to follow-up on epidemiologic analyses in clinic-based cohorts: the case of HIV-infected patients on antiretroviral therapy in Africa. AB - Although clinic-based cohorts are most representative of the "real world," they are susceptible to loss to follow-up. Strategies for managing the impact of loss to follow-up are therefore needed to maximize the value of studies conducted in these cohorts. The authors evaluated adult patients starting antiretroviral therapy at an HIV/AIDS clinic in Uganda, where 29% of patients were lost to follow-up after 2 years (January 1, 2004-September 30, 2007). Unweighted, inverse probability of censoring weighted (IPCW), and sampling-based approaches (using supplemental data from a sample of lost patients subsequently tracked in the community) were used to identify the predictive value of sex on mortality. Directed acyclic graphs (DAGs) were used to explore the structural basis for bias in each approach. Among 3,628 patients, unweighted and IPCW analyses found men to have higher mortality than women, whereas the sampling-based approach did not. DAGs encoding knowledge about the data-generating process, including the fact that death is a cause of being classified as lost to follow-up in this setting, revealed "collider" bias in the unweighted and IPCW approaches. In a clinic-based cohort in Africa, unweighted and IPCW approaches-which rely on the "missing at random" assumption-yielded biased estimates. A sampling-based approach can in general strengthen epidemiologic analyses conducted in many clinic-based cohorts, including those examining other diseases. PMID- 22306559 TI - Re: "Longitudinal health study of US 1991 Gulf War veterans: changes in health status at 10-year follow-up". PMID- 22306561 TI - Invited commentary: Lost in estimation--searching for alternatives to markov chains to fit complex Bayesian models. AB - Bayesian methods have seen an increase in popularity in a wide variety of scientific fields, including epidemiology. One of the main reasons for their widespread application is the power of the Markov chain Monte Carlo (MCMC) techniques generally used to fit these models. As a result, researchers often implicitly associate Bayesian models with MCMC estimation procedures. However, Bayesian models do not always require Markov-chain-based methods for parameter estimation. This is important, as MCMC estimation methods, while generally quite powerful, are complex and computationally expensive and suffer from convergence problems related to the manner in which they generate correlated samples used to estimate probability distributions for parameters of interest. In this issue of the Journal, Cole et al. (Am J Epidemiol. 2012;175(5):368-375) present an interesting paper that discusses non-Markov-chain-based approaches to fitting Bayesian models. These methods, though limited, can overcome some of the problems associated with MCMC techniques and promise to provide simpler approaches to fitting Bayesian models. Applied researchers will find these estimation approaches intuitively appealing and will gain a deeper understanding of Bayesian models through their use. However, readers should be aware that other non-Markov chain-based methods are currently in active development and have been widely published in other fields. PMID- 22306562 TI - Interaction and exposure modification: are we asking the right questions? AB - Most diseases arise not purely through genetic abnormalities nor purely through environmental causes, but as "complex" conditions brought about by the combined effects of genetic susceptibility factors, nongenetic experiences and exposures, and bad luck. Finding simple models capable of both characterizing such joint effects and providing new insight into pathogenesis remains an ongoing challenge in etiologic epidemiology. Additive null models can capture certain pure forms of independent etiologic effects in studies of rare conditions and can be useful for predicting possible effects of interventions. The concept of exposure modification is here proposed as useful, particularly in thinking about biologic interactions between exposures and genetic variants. Openness to parsimonious joint models and the insights they can provide is key to advancing our understanding of etiology. PMID- 22306563 TI - Endogenous reproductive hormones and C-reactive protein across the menstrual cycle: the BioCycle Study. AB - C-reactive protein (CRP) is one of the most commonly used markers of acute phase reaction in clinical settings and predictors of cardiovascular risk in healthy women; however, data on its physiologic regulation in premenopausal women are sparse. The objective of this study was to evaluate the association between endogenous reproductive hormones and CRP in the BioCycle Study (2005-2007). Women aged 18-44 years from western New York were followed prospectively for up to 2 menstrual cycles (n = 259). Serum levels of CRP, estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone were measured up to 8 times per cycle, timed by fertility monitors. CRP levels varied significantly across the cycle (P < 0.001). More women were classified as being at elevated risk of cardiovascular disease (CRP, >3 mg/L) during menses compared with other phases (12.3% vs. 7.4%; P < 0.001). A 10-fold increase in estradiol was associated with a 24.3% decrease in CRP (95% confidence interval: 19.3, 29.0). A 10-fold increase in luteal progesterone was associated with a 19.4% increase in CRP (95% confidence interval: 8.4, 31.5). These results support the hypothesis that endogenous estradiol might have antiinflammatory effects and highlight the need for standardization of CRP measurement to menstrual cycle phase in reproductive aged women. PMID- 22306564 TI - Genetic variants on 15q25.1, smoking, and lung cancer: an assessment of mediation and interaction. AB - Genome-wide association studies have identified variants on chromosome 15q25.1 that increase the risks of both lung cancer and nicotine dependence and associated smoking behavior. However, there remains debate as to whether the association with lung cancer is direct or is mediated by pathways related to smoking behavior. Here, the authors apply a novel method for mediation analysis, allowing for gene-environment interaction, to a lung cancer case-control study (1992-2004) conducted at Massachusetts General Hospital using 2 single nucleotide polymorphisms, rs8034191 and rs1051730, on 15q25.1. The results are validated using data from 3 other lung cancer studies. Tests for additive interaction (P = 2 * 10(-10) and P = 1 * 10(-9)) and multiplicative interaction (P = 0.01 and P = 0.01) were significant. Pooled analyses yielded a direct-effect odds ratio of 1.26 (95% confidence interval (CI): 1.19, 1.33; P = 2 * 10(-15)) for rs8034191 and an indirect-effect odds ratio of 1.01 (95% CI: 1.00, 1.01; P = 0.09); the proportion of increased risk mediated by smoking was 3.2%. For rs1051730, direct- and indirect-effect odds ratios were 1.26 (95% CI: 1.19, 1.33; P = 1 * 10(-15)) and 1.00 (95% CI: 0.99, 1.01; P = 0.22), respectively, with a proportion mediated of 2.3%. Adjustment for measurement error in smoking behavior allowing up to 75% measurement error increased the proportions mediated to 12.5% and 9.2%, respectively. These analyses indicate that the association of the variants with lung cancer operates primarily through other pathways. PMID- 22306565 TI - Bayesian posterior distributions without Markov chains. AB - Bayesian posterior parameter distributions are often simulated using Markov chain Monte Carlo (MCMC) methods. However, MCMC methods are not always necessary and do not help the uninitiated understand Bayesian inference. As a bridge to understanding Bayesian inference, the authors illustrate a transparent rejection sampling method. In example 1, they illustrate rejection sampling using 36 cases and 198 controls from a case-control study (1976-1983) assessing the relation between residential exposure to magnetic fields and the development of childhood cancer. Results from rejection sampling (odds ratio (OR) = 1.69, 95% posterior interval (PI): 0.57, 5.00) were similar to MCMC results (OR = 1.69, 95% PI: 0.58, 4.95) and approximations from data-augmentation priors (OR = 1.74, 95% PI: 0.60, 5.06). In example 2, the authors apply rejection sampling to a cohort study of 315 human immunodeficiency virus seroconverters (1984-1998) to assess the relation between viral load after infection and 5-year incidence of acquired immunodeficiency syndrome, adjusting for (continuous) age at seroconversion and race. In this more complex example, rejection sampling required a notably longer run time than MCMC sampling but remained feasible and again yielded similar results. The transparency of the proposed approach comes at a price of being less broadly applicable than MCMC. PMID- 22306566 TI - Smoking reduction at midlife and lifetime mortality risk in men: a prospective cohort study. AB - Previous studies have not shown a survival advantage for smoking reduction. The authors assessed survival and life expectancy according to changes in smoking intensity in a cohort of Israeli working men. Baseline smokers recruited in 1963 were reassessed in 1965 (n = 4,633; mean age, 51 years) and followed up prospectively for mortality through 2005. Smoking intensity at both time points was self-reported and categorized as none, 1-10, 11-20, and >=21 cigarettes per day. Change between smoking categories was noted, and participants were classified as increased (8%), maintained (65%), reduced (17%), or quit (10%) smoking. During a median follow-up of 26 (quartiles 1-3: 16-35) years, 87% of participants died. Changes in intensity were associated with survival. In multivariable-adjusted models, the hazard ratios for mortality were 1.14 (95% confidence interval (CI): 0.99, 1.32) among increasers, 0.85 (95% CI: 0.77, 0.95) among reducers, and 0.78 (95% CI: 0.69, 0.89) among quitters, compared with maintainers. Inversely, the adjusted odds ratios of surviving to age 80 years were 0.77 (95% CI: 0.60, 0.98), 1.22 (95% CI: 1.01, 1.47), and 1.33 (95% CI: 1.07, 1.66), respectively. The survival benefit associated with smoking reduction was mostly evident among heavy smokers and for cardiovascular disease mortality. These results suggest that decreasing smoking intensity should be considered as a risk-reduction strategy for heavy smokers who cannot quit abruptly. PMID- 22306567 TI - [Clinical, laboratory and computed tomography pulmonary angiography results in pulmonary embolism: retrospective evaluation of 205 patients]. AB - OBJECTIVE: With this study, we aimed at evaluating demographic data, clinical, laboratory findings in pulmonary embolism (PE) and the relationship of these findings with the embolism location region and responses of the patients to the treatment of the embolism in order to contribute to the patient management in decreasing mortality. METHODS: Clinical findings, accompanying diseases, risk factors, serum D-dimer and creatinine levels, imaging modalities and mortality rates of 205 patients (female: 98, male: 107) diagnosed with PE were examined retrospectively. The relationship between the qualifier variables was evaluated using Chi-square test. RESULTS: Average age of the patients was 61.55+/-14.44 years and 86 (42%) patients were above 65 years. Most common complaint was dyspnea (85%), most frequent coexisting disease was congestive heart failure (19%). Deep vein thrombosis (DVT) (30.7%) was the most frequently seen risk factor. Pulmonary embolism was mostly in the right lobe pulmonary artery (32.1%). It was observed that the higher ages of patients the more frequency of proximal located embolism was (p<0.005), especially lobar artery involvement was observed to be high (p=0.032). An early mortality rate was 4.9% and late mortality rate was 11.2%. CONCLUSION: In the patients with complaint of dyspnea who are at elder ages and have accompanying diseases, PE should be considered. PE is generally localized in the main pulmonary arteries, which emphasizes crucial importance of early diagnosis and treatment in reduction of mortality. PMID- 22306568 TI - [The association between pulmonary arterial hypertension and malnutrition in children with congenital heart diseases with left-to-right shunt: an observational study]. AB - OBJECTIVE: To evaluate the association between the degree of pulmonary arterial hypertension (PAH) and the level of malnutrition in children with acyanotic congenital heart diseases and left-to-right shunt, and especially to evaluate the development rates of malnutrition in patients with borderline PAH. METHODS: The study was performed with data of 327 patients with acyanotic congenital heart diseases and left-to-right shunt and underwent cardiac catheterization between January 2001-February 2011. The design of the study was retrospective and observational. All patients were evaluated with anthropometric measurements, echocardiography and cardiac catheterization. They were classified according to the mean pulmonary artery pressure and level of malnutrition. Chi-square, ANOVA and Kruskal-Wallis tests were used for statistical analysis. Normally and abnormally distributed data were analyzed with Pearson and Spearman correlation tests respectively. RESULTS: Malnutrition was detected in 94.8% of patients with PAH and 17.2% of no PAH patients according to Gomez classification (p<0.001). In addition, malnutrition was detected in 23.5% (16/68) of borderline PAH group. A negative association was detected between mean pulmonary arterial pressure and body weight for age (Gomez) and z scores of weight (p<0.001 for all). Z scores of weight and height were significantly decreased in patients with PAH in contrast to no PAH group (p<0.001, p<0.01 respectively). There was no statistical difference between no PAH and borderline PAH groups according to Gomez classification and relative body weight formula, however z scores of weight in borderline PAH group were decreased compared with no PAH group (p<0.001). CONCLUSION: A positive association was detected between the degrees of PAH and level of malnutrition in children with a cyanotic congenital heart diseases with left-to-right shunt. Borderline PAH may be a predisposing factor for malnutrition and further studies are needed for this subject. PMID- 22306569 TI - An observational study on peripheral blood eosinophilia in incomplete Kawasaki disease. AB - OBJECTIVE: To investigate the peripheral blood eosinophilia (PBE) in the acute stage of incomplete Kawasaki disease (iKD). METHODS: Twenty-four patients with iKD (median age; 31.5 months, range; 7-88 months) and 25 with complete Kawasaki disease (cKD) (median age; 37 months, range; 9-140 months) were evaluated between 2004 and 2010 from Izmir Dr. Behcet Uz Children's Hospital records retrospectively. We determined the eosinophil counts and rates from the complete blood count in two study groups before the IVIG treatment and 30 febrile age matched controls and 30 control cases with congenital heart disease (control Group 1 and 2 respectively). Kruskal-Wallis test was performed in detecting the differences of eosinophil rates and counts between four subgroups. RESULTS: In iKD group, the mean value of eosinophil rates and median value of eosinophil counts were 4.39+/-2.5% and 377 cells/mm(3), respectively, which did not significantly different with cKD group (mean eosinophil rates; 5.47+/-4.8% and median eosinophil counts 525 cells/mm(3)) (p>0.05). The median values of eosinophil cell counts and mean value of eosinophil rates were 220 cell/mm(3) and 2.83+/-2.65% in the control group 1 and 165 cell/mm(3) and 1.63+/-1.43% in the control Group 2 respectively, which were statistically significant lower compared to both study groups (p< 0.001). CONCLUSION: The rate of PBE was found significantly higher in iKD patients compared to the controls. Since the diagnosis of iKD is difficult, unexplained eosinophilia may be helpful in the presence of suggestive clinical findings of KD. PMID- 22306570 TI - [The effects of implanted valve sizes on ventricular hypertrophy in aortic stenosis]. AB - OBJECTIVE: We aimed to study the effects of the valve sizes according to body surface area on aortic gradient and ventricular hypertrophy in the cases of aortic valve replacement due to isolated aortic stenosis. METHODS: Between January 2006 and April 2007, patients (12 men, 15 women; totally 27) followed up prospectively with echocardiography fourth and sixth month postoperatively. The patients were divided into two groups according to the prosthetic aortic valve diameters (19-21 mm vs 23-25 mm). The primary endpoints between the two groups (aortic regurgitation, left ventricular mass index and transvalvular gradient measured by color and continuous wave Doppler) were compared. Fischer exact test and Mann-Whitney U test were used for intergroup comparison whereas intragroup analysis was done with Freidman test. RESULTS: Mean systolic gradient and left ventricular mass index were significantly reduced in 23 mm and 25 mm valves (p<0.01) in the postoperative follow-up. In addition, especially, decline in the values of left ventricular mass, left ventricular mass index, peak systolic gradient and the mean systolic gradient were found to be significant. These values associated with regression were detectable at the postoperative 4th month, but actual significant regression was observed at the postoperative 6th month (p<0.01). On the other hand, the values obtained for 19 mm and 21 mm valves also showed significant progress (p<0.05). CONCLUSION: Factors such as age, gender and activity are important in the selection of appropriate valve sizes in aortic valve replacement. However, the patient's body surface is the most important prognostic factor compared to others. PMID- 22306571 TI - [Coronary artery disease from a perspective of genomic risk score, ethical approaches and suggestions]. AB - As a leading cause of mortality, coronary artery disease is on the focus of genetic research as a complex trait. Although predictive genetic testing for cardiovascular diseases is on the counter, it is still hard to aggregate information from multiple genetic variants, environmental factors and family history into a single score. Every susceptibility allele provides small contribution to disease formation. Biomarkers play a role in various metabolic pathways. Genetic information and data depend heavily on probabilities. This should be clearly explained by genetic counselor to the patient and relatives who are looking for certain answers. Presence of susceptibility alleles can be a source of anxiety and it may result as a reduced self-confidence in ability to change health behavior. Complex diseases set a new stage to study novel techniques that can elucidate interactions among genetic, environmental and ethnic factors. The cookbook approach to treat a complex disease can often be misleading. Future studies may provide personalized information, which can improve the outcome of standardized treatments. As knowing one's own genetic risk is becoming a task for the responsible individual, it surely will add new challenges to ethical framework. Publicly marketing genetic tests for complex diseases raises ethical concerns. To avoid discriminatory use of genetic information; genetic risk scoring, therapeutic process, ethical policies must have a multifaceted progress. In this review, we summarized the attempts to resolve ethical issues related to genetic testing in complex diseases to resolve patient autonomy with individual responsibility and to aim the patient beneficence and confidentiality. PMID- 22306572 TI - [Evolution of restricted bulboventricular foramen in double inlet left ventricle and ventriculoarterial discordance]. PMID- 22306573 TI - Tubular atrophy and interstitial fibrosis after renal transplantation is dependent on galectin-3. AB - BACKGROUND: Chronic allograft injury (CAI), characterized by interstitial fibrosis and tubular atrophy, leads to a progressive decline in graft function, resulting in the loss of 5% of renal transplants per annum, and eludes specific therapies. Galectin-3 (gal-3) is a beta-galactoside-binding lectin expressed in diverse fibrotic tissue, and mice deficient in gal-3 have reduced fibrosis in kidney, liver, and lung models. The role of gal-3 in CAI is examined in this study. METHODS: We adopted a murine model of CAI, characterized by a single class II mismatch between BM12 donor and C57BL/6 recipient strains. Syngeneic transplants served as controls (C57BL/6). Transplants were then performed between BM12 donors and gal-3 null recipients on a C57BL/6 background. RESULTS: Transplantation of BM12 kidneys into C57BL6 mice was associated with interstitial fibrosis (P<0.0001), tubular atrophy (P<0.0001), and upregulation in gal-3 expression (P=0.002), compared with syngeneic controls. Transplanting BM12 kidneys into gal-3 null mice resulted in significant preservation of tubules (P=0.008) and reduced interstitial fibrosis (P=0.01), with decreased myofibroblast activation (P=0.01) and collagen I expression (P=0.04), compared with wild type controls. The number of infiltrating leukocytes was unaltered by abrogation of gal-3, but reduced expression of YM1 (P=0.0001), a marker of alternative macrophage activation, along with a reduction in the number of circulating CD4-positive T cells (P=0.01), and reduced expression of interleukin 4 (P=0.02) in gal-3 null mice suggest possible mechanisms by which gal-3 may promote renal transplant fibrosis. CONCLUSION: Our results suggest a potential role for gal-3 in CAI, and this represents a potentially exciting therapeutic target. PMID- 22306574 TI - Effects of antibody induction on transplant outcomes in human leukocyte antigen zero-mismatch deceased donor kidney recipients. AB - BACKGROUND: We aimed to investigate the impact of antibody induction on outcomes in human leukocyte antigen (HLA) 0-mismatched deceased donor kidney recipients. METHODS: Using the Organ Procurement and Transplant Network/United Network of Organ Sharing database as of November 2009, we identified 44,008 adult deceased donor kidney recipients who received primary kidney transplants alone between 2003 and 2008 (HLA 0 mismatch, n = 6274; >= 1 mismatch, n=37,734; median follow up: 834 days). The impact of induction (thymoglobulin, interleukin-2 receptor antagonists [IL-2RA], or alemtuzumab; vs. no induction) on rejection (initial hospitalization, 6 months, first year), death-censored graft failure, and mortality were analyzed using multivariate logistic and Cox regression in the two groups. The impact of individual agents on outcomes was further analyzed in 0 mismatch recipients. RESULTS: There was a decreased risk of rejection over the first 6 months for HLA 0-mismatch recipients of antibody induction (adjusted odds ratio=0.71, P=0.003), but this effect was not observed at 1 year; in comparison, induction was associated with a reduced risk of rejection over the first year for HLA-mismatched recipients (0.87, P<0.001). The use of thymoglobulin (0.72, P=0.02) and IL-2RA (0.67, P=0.004) was associated with a decreased risk of rejection compared with no-induction at 6 months but was not different at 1 year (thymoglobulin: 0.77, P=0.05; IL-2RA:0.81, P=0.11) in HLA 0-mismatched recipients. Induction was not associated with improved graft or patient survival in HLA 0-mismatch recipients. CONCLUSION: In HLA 0-mismatch deceased donor recipients, antibody induction was associated with a decreased risk of rejection at 6 months posttransplant. Its use did not improve graft and patient survival over the follow-up period. PMID- 22306575 TI - Sequential spiking neural P systems with exhaustive use of rules. AB - Spiking neural P systems (SN P systems, for short) are a class of distributed parallel computing devices inspired from the way neurons communicate by means of spikes, where neurons work in parallel in the sense that each neuron that can fire should fire, but the work in each neuron is sequential in the sense that at most one rule can be applied at each computation step. In this work, we consider SN P systems with the restriction that at most one neuron can fire at each step, and each neuron works in an exhaustive manner (a kind of local parallelism - an applicable rule in a neuron is used as many times as possible). Such SN P systems are called sequential SN P systems with exhaustive use of rules. The computation power of sequential SN P systems with exhaustive use of rules is investigated. Specifically, characterizations of Turing computability and of semilinear sets of numbers are obtained, as well as a strict superclass of semilinear sets is generated. The results show that the computation power of sequential SN P systems with exhaustive use of rules is closely related with the types of spiking rules in neurons. PMID- 22306576 TI - Role of ERbeta and GPR30 in the endocrine pancreas: A matter of estrogen dose. AB - The endocrine pancreas has emerged as a target for estrogens. The functions of pancreatic alpha-, beta- and delta-cells are modulated by the endogenous hormone, 17beta-estradiol (E2). Low physiological concentrations (100pM-1nM) of E2 rapidly decrease the activity of the ATP-sensitive potassium channel (K(ATP)) and enhance glucose-induced insulin release in beta-cells in an estrogen receptor beta (ERbeta)-dependent manner. In addition to the insulinotropic action of ERbeta, the newly described estrogen receptor, GPR30, is involved in the insulinotropic effects of high doses of E2 (100nM-5MUM). The specific GPR30 agonist G1 also increases insulin secretion in beta-cells. Low glucose-induced calcium oscillations and glucagon secretion are suppressed by E2. The effects on glucagon secretion may be mediated by GPR30. Somatostatin release is also decreased by E2 and G1. In this review we summarize all the data published up to date on the rapid insulinotropic effects of estrogens in the endocrine pancreas and propose a model to integrate the estrogen actions mediated through both receptors. PMID- 22306577 TI - Calcium-induced activation of estrogen receptor alpha--New insight. AB - Calcium being an important modulator in multiple regulatory processes, we overviewed reported investigations concerning its potential influence on ERalpha transcriptional activity in breast cancer cells. Three main activating mechanisms depending on either intra- or extracellular calcium are described. At physiological intracellular concentration (MUM), Ca(++) activates calmodulin and promotes its association with ERalpha; the resulting complex stably interacts with EREs at promoter sites, giving rise to enhanced transcription of estrogen target genes. Hypercalcemic concentrations (mM) produce a similar response through a direct association of the ion with the ligand binding domain of the receptor, this binding of calcium conferring an active conformation to ER. In contrast to these intracellular processes, very high extracellular concentrations of Ca(++) (>10mM) detected in bones at time of tumor metastasis operate via a signal transduction pathway initiated at the cell membrane through a specific activation of the calcium-sensing receptor. PMID- 22306578 TI - Polyproline and Tat transduction peptides in the study of the rapid actions of steroid receptors. AB - Cellular responses to signals require the action of a myriad of protein networks, which are regulated by protein/protein associations. Rapid actions of steroid hormones are also subject to this regulation. They induce direct association of steroid receptors with different proteins (e.g., growth factor receptors, signaling effectors, scaffold proteins, transcription factors). These multi molecular complexes drive signaling activation and finally trigger basic hormonal effects. Receptor/protein associations are attracting increased interest concerning their role in hormone action as well as their potential use as therapeutic targets in hormonal diseases. PMID- 22306579 TI - Computational redesign of a mononuclear zinc metalloenzyme for organophosphate hydrolysis. AB - The ability to redesign enzymes to catalyze noncognate chemical transformations would have wide-ranging applications. We developed a computational method for repurposing the reactivity of metalloenzyme active site functional groups to catalyze new reactions. Using this method, we engineered a zinc-containing mouse adenosine deaminase to catalyze the hydrolysis of a model organophosphate with a catalytic efficiency (k(cat)/K(m)) of ~10(4) M(-1) s(-1) after directed evolution. In the high-resolution crystal structure of the enzyme, all but one of the designed residues adopt the designed conformation. The designed enzyme efficiently catalyzes the hydrolysis of the R(P) isomer of a coumarinyl analog of the nerve agent cyclosarin, and it shows marked substrate selectivity for coumarinyl leaving groups. Computational redesign of native enzyme active sites complements directed evolution methods and offers a general approach for exploring their untapped catalytic potential for new reactivities. PMID- 22306580 TI - Small-molecule-induced DNA damage identifies alternative DNA structures in human genes. AB - Guanine-rich DNA sequences that can adopt non-Watson-Crick structures in vitro are prevalent in the human genome. Whether such structures normally exist in mammalian cells has, however, been the subject of active research for decades. Here we show that the G-quadruplex-interacting drug pyridostatin promotes growth arrest in human cancer cells by inducing replication- and transcription-dependent DNA damage. A chromatin immunoprecipitation sequencing analysis of the DNA damage marker gammaH2AX provided the genome-wide distribution of pyridostatin-induced sites of damage and revealed that pyridostatin targets gene bodies containing clusters of sequences with a propensity for G-quadruplex formation. As a result, pyridostatin modulated the expression of these genes, including the proto oncogene SRC. We observed that pyridostatin reduced SRC protein abundance and SRC dependent cellular motility in human breast cancer cells, validating SRC as a target of this drug. Our unbiased approach to define genomic sites of action for a drug establishes a framework for discovering functional DNA-drug interactions. PMID- 22306581 TI - Poisoning by Jatropha ribifolia in goats. AB - Human poisoning by Jatropha species and poisoning when livestock have been fed processed plant material has been described. Additionally, poisoning has been experimentally reproduced in various animal models. But, no cases of poisoning in livestock grazing standing and unprocessed Jatropha spp. has been reported. This study reports the poisoning of goats with Jatropha ribifolia in the semiarid region of northeastern Brazil during the dry season. The mortality of the goats ranged from 6% to 40%. The main clinical signs were apathy, anorexia, soft feces, weight loss, and severe dehydration. The skin, lips, horns, and teeth of the affected goats were stained with a reddish pigment that is present in the J. ribifolia plant. Emaciation was the main lesion observed in one necropsied goat. In 2 out of 3 goats that ingested a single dose of J. ribifolia, 10 g or 20 g of leaves of the plant per kg body weight (g/kg), mild dehydration and soft feces were observed. The plant was also administered daily to two goats for 8 days. One animal received 10 g/kg per day, and the other received 20 g/kg per day and the goats showed clinical signs after 4 and 3 days, respectively. The goat that received 10 g/kg daily recovered, and the other was euthanized. The clinical signs and lesions that were observed were similar to those observed in the spontaneous cases. This is the first case of Jatropha spp. poisoning in grazing animals that ingested the plant spontaneously. PMID- 22306582 TI - Assessment of antioxidant capacity for scavenging free radicals in vitro: a rational basis and practical application. AB - With increasing evidence showing the involvement of oxidative stress induced by free radicals in the development of various diseases, the role of radical scavenging antioxidants has received much attention. Although many randomized controlled clinical trials do not support the beneficial effects of indiscriminate supplementation of antioxidants, more recent studies suggest that antioxidants such as vitamin E may be effective for prevention and treatment of some diseases when given to the right subjects at the right time. Many studies on the antioxidant capacity assessed by various available methods showed inconsistent results and the assessment of antioxidant capacity has been the subject of extensive studies and arguments. This study was performed to elucidate the basic chemistry required for the development of a reliable method for the assessment of antioxidant capacity for radical scavenging in vitro. In this study, the capacity of alpha-tocopherol and its related compounds, ascorbic acid, and uric acid for scavenging radicals was assessed from their effects on the rate of decay of hydrophilic and lipophilic probes with various reactivities toward free radicals induced by hydrophilic and lipophilic radicals in homogeneous solution and heterogeneous micelle systems. Fluorescein, pyranine, and pyrogallol red were used as hydrophilic probes, and BODIPY and N,N-diphenyl-p phenylenediamine were used as lipophilic probes. We show that the rate and amount of radical scavenging by antioxidants, termed the antioxidant radical absorbance capacity, could be assessed by an appropriate combination of radical initiator and probe. This method was applied to the assessment of radical-scavenging capacity of human plasma, wine, and green tea powder. PMID- 22306583 TI - Cost-effectiveness of adding an agent that improves immune responses to initial antiretroviral therapy (ART) in HIV-infected patients: guidance for drug development. AB - PURPOSE: Adding an immune-enhancing agent to initial antiretroviral therapy (ART) for HIV is a potential strategy to ensure that patients achieve optimal immune response. METHOD: Using a mathematical model of HIV disease and treatment, we evaluated the treatment benefits and cost-effectiveness of adding a hypothetical immune-enhancing agent to the initial 6 months of ART. We assumed that the additional agent would result in a higher CD4 increase that would provide clinical benefit. The additional cost ($1,900/month) was based on the cost of a drug currently under investigation for immune enhancement. Outcomes included projected life expectancy and cost-effectiveness in 2009 US dollars/quality adjusted life year (QALY) with costs and QALYs discounted at 3% annually. RESULTS: Compared to standard ART, immune-enhanced ART resulting in an additional 40 CD4 cell/uL increase at 6 months yields a 2.4 month projected undiscounted life expectancy increase with a cost-effectiveness ratio of $107,600/QALY. Achieving a cost-effectiveness ratio <$100,000/QALY requires a >43 CD4 cell/uL improvement, or >19 cells/uL if immune-enhancing agent costs are halved. CONCLUSIONS: In addition to showing clinical efficacy, investigational immune enhancement agents need to increase CD4 counts more than has been previously observed or have a lower cost to be considered cost-effective in the United States. PMID- 22306584 TI - Cost-effectiveness of a fourth-generation combination immunoassay for human immunodeficiency virus (HIV) antibody and p24 antigen for the detection of HIV infections in the United States. AB - PURPOSE: The US Food and Drug Administration recently approved the first 4th generation HIV test. This study evaluated the cost-effectiveness of the 4th generation assay versus a 3rd-generation test in screening for HIV infections in the United States. METHODS: An exploratory microsimulation model was developed that follows hypothetical individuals and simulates the course of HIV/AIDS, treatment with highly active antiretroviral therapy, and transmissions. RESULTS: With a 1% HIV prevalence, screening 1.5 million individuals with the 4th- versus 3rd-generation assay resulted in detection of 266 additional HIV cases at an incremental cost per additional HIV case detected of $63,763, an additional 489 life years and 395 quality-adjusted life years (QALYs), and 26 HIV transmissions prevented. Although lifetime costs were increased by $33.6 million, the incremental cost/QALY gained was $85,206. The 4th-generation test was more cost effective in high incidence settings. The number needed to screen to detect one additional HIV case was 5,635. CONCLUSIONS: Screening using the 4th-generation assay may be cost-effective for HIV detection in appropriate settings, resulting in increased case identification, fewer transmissions, extended life, and increased quality of life. With early and accurate detection, this 4th-generation test may provide a suitable alternative to current 3rd-generation tests. PMID- 22306585 TI - High-level immunogenicity is achieved vaccine with adjuvanted pandemic H1N1(2009) and improved with booster dosing in a randomized trial of HIV-infected adults. AB - BACKGROUND: More severe influenza disease and poor vaccine immunogenicity in HIV infected patients necessitate improved immunization strategies to maximize vaccine efficacy. METHODS: A phase III, randomized trial was conducted at 4 Canadian sites. Two dosing strategies (standard dose vs standard dose plus booster on day 21) were assessed in HIV patients aged 20 to 59 years during the H1N1(2009) pandemic. A single antigen, inactivated split adjuvanted (AS03(A)) influenza vaccine (Arepanrix) was utilized. Serum hemagglutination inhibition (HAI) titres were assessed at days 21 and 42 and at month 6. RESULTS: 150 participants received at least one injection. Baseline parameters were similar between groups: 83% male, 85% on HAART, median CD4 = 519 cells/mm(3), 84% with HIV RNA < 50 copies/mL. At day 21, seroprotection (HAI >=1:40) was achieved in 80% (95% CI, 70-89) of participants. Seroconversion occurred in 74% (63-85). Seroprotection and seroconversion were further improved in those randomized to booster dosing: day 42, 94% (85-98) versus 73% (60-83) (P < .01) and 86% (75-93) versus 66% (5-77) (P = .01). Seroprotec-tion was retained in 40% (28-54) of recipients at month 6 with trends toward greater retention of immunity in booster recipients. CONCLUSION: High-level immunogenicity was achieved with a single dose of this adjuvanted vaccine. Immunogenicity was further improved with booster dosing. Use of this adjuvanted vaccine and booster represent an important approach to increasing immunogenicity in this vaccine hypo-responsive population. PMID- 22306586 TI - The dose-response relationship of peginterferon alfa-2a and ribavirin in the treatment of patients coinfected with HIV-HCV. AB - PURPOSE: The relationship between peginterferon/ribavirin exposure and the probability of achieving a sustained virologic response (SVR) in HIV-HCV coinfected patients is not well described. We conducted a retrospective analysis of HIV-HCV coinfected patients randomized to 48 weeks of treatment with peginterferon alfa-2a (40 kD) 180 ug/week and ribavirin 800 mg/day in the multinational APRICOT study to define optimal exposure thresholds. METHOD: Actual drug exposure was estimated in 287 patients, taking into consideration dose reductions for adverse events or laboratory abnormalities. RESULTS: SVR overall and SVR in those completing treatment was, respectively, 29% and 37% among HCV genotype-1 patients and 59% and 68% among genotype non-1 patients. No patients with <=40% exposure to ribavirin achieved an SVR. Receiver operating characteristic analysis identified that threshold exposures to both drugs of >75% (genotype-1) and >60% (genotype non-1) are associated with SVR. An existing generalized additive model populated with data from HCV monoinfected patients was updated to predict an overall SVR of 37% if genotype-1 patients received ribavirin 1000 or 1200 mg/day but at the cost of a higher incidence of anemia (23%). CONCLUSION: Completion of scheduled treatment and exceeding certain thresholds for exposure to peginterferon alfa 2a (40 kD) and ribavirin is associated with higher SVR rates. PMID- 22306587 TI - Safety and pharmacokinetics of nelfinavir during the second and third trimesters of pregnancy and postpartum. AB - PURPOSE: Evaluate the safety, tolerability, and pharmacokinetics (PK) of nelfinavir during pregnancy and postpartum in HIV-infected women. METHODS: Phase IV, non-randomized, open-label study of nelfinavir 625 mg tablets (1250 mg) in combination with lamivudine/zidovudine twice daily. Primary endpoint was treatment-related or possibly treatment-related gastrointestinal or hepatic adverse events (AEs). Selected maternal and infant outcomes were recorded. Frequent plasma samples were collected for PK studies during the 2nd and 3rd trimesters, and 6 weeks postpartum, to analyze total and free nelfinavir and M8 concentrations. RESULTS: Sixteen HIV+ pregnant women were enrolled. Six mild treatment-related AEs and 3 serious AEs occurred; 1 serious AE (elevated AST) met the primary endpoint. Compared with 6 weeks postpartum, levels of total nelfinavir were reduced by 44% and 46%, total M8 by 82% and 83%, free nelfinavir by 48% and 39%, and free M8 by 83% and 79% in the 2nd and 3rd trimesters, respectively. At 6 weeks postpartum, 75% and 50% of subjects maintained HIV-1 RNA levels <400 and <50 copies/mL, respectively. All pregnancies resulted in live births without transmission in 15 infants. CONCLUSIONS: Nelfinavir in combination with lamivudine/zidovudine was generally well tolerated. Total and free nelfinavir and M8 exposure were reduced in late pregnancy. PMID- 22306588 TI - [A tool for supporting decision making for occupational health practitioners at the occurrence of novel influenza]. PMID- 22306589 TI - Evolutionarily stable learning schedules and cumulative culture in discrete generation models. AB - Individual learning (e.g., trial-and-error) and social learning (e.g., imitation) are alternative ways of acquiring and expressing the appropriate phenotype in an environment. The optimal choice between using individual learning and/or social learning may be dictated by the life-stage or age of an organism. Of special interest is a learning schedule in which social learning precedes individual learning, because such a schedule is apparently a necessary condition for cumulative culture. Assuming two obligatory learning stages per discrete generation, we obtain the evolutionarily stable learning schedules for the three situations where the environment is constant, fluctuates between generations, or fluctuates within generations. During each learning stage, we assume that an organism may target the optimal phenotype in the current environment by individual learning, and/or the mature phenotype of the previous generation by oblique social learning. In the absence of exogenous costs to learning, the evolutionarily stable learning schedules are predicted to be either pure social learning followed by pure individual learning ("bang-bang" control) or pure individual learning at both stages ("flat" control). Moreover, we find for each situation that the evolutionarily stable learning schedule is also the one that optimizes the learned phenotype at equilibrium. PMID- 22306590 TI - On ordered subpopulations and population mortality at advanced ages. AB - We consider hazard (mortality) rates in heterogeneous populations consisting of ordered (in the defined stochastic sense) subpopulations. This setting can be interpreted via the fixed frailty models with one or more frailty parameters. The shape of the hazard rate is of main interest in this paper. Specifically, the deceleration and leveling off in the hazard rates (mortality plateaus) are discussed and some examples of lifetime distributions that can result in asymptotically flat hazard rates are considered. These examples are based on vitality models when an organism's initial vitality (resource) is 'consumed' in the course of life in accordance with a simple stochastic process (e.g., the Wiener process with drift or the gamma process). PMID- 22306591 TI - Estimating the unmeasured membrane potential of neuronal populations from the EEG using a class of deterministic nonlinear filters. AB - We present a model-based estimation method to reconstruct the unmeasured membrane potential of neuronal populations from a single-channel electroencephalographic (EEG) measurement. We consider a class of neural mass models that share a general structure, specifically the models by Stam et al (1999 Clin. Neurophysiol. 110 1801-13), Jansen and Rit (1995 Biol. Cybern. 73 357-66) and Wendling et al (2005 J. Clin. Neurophysiol. 22 343). Under idealized assumptions, we prove the global exponential convergence of our filter. Then, under more realistic assumptions, we investigate the robustness of our filter against model uncertainties and disturbances. Analytic proofs are provided for all results and our analyses are further illustrated via simulations. PMID- 22306592 TI - Opt-in or opt-out for organ transplantation. AB - PURPOSE OF REVIEW: Opt-in or opt-out consent for organ transplantation is still a disputed subject and the determination of the more appropriate system is still debated. RECENT FINDINGS: Europe is still divided between countries where transplantation after brain death is governed by presumed consent and other where informed consent is mandatory. Recent debate, however, has emerged in each country to determine whether shifting systems might be beneficial for organ procurement. SUMMARY: Consent for organ donation in a brain dead patient represents an act of benevolence or of solidarity in favour of an unknown person. If one considers that the principle of autonomy must prevail over the principle of benevolence or of solidarity, the risk is depriving a potential recipient of a comparatively very important benefit. On the contrary, if one considers that the principles of benevolence should necessarily lead, the risk is high of exerting an excessive pressure to the detriments of autonomy and liberty of the individual. Whatever the system chosen, adequate and fair communication expressing loyally the way families are approached is essential. PMID- 22306593 TI - Money, money, money. PMID- 22306594 TI - Red blood cell transfusion in the bleeding traumatized patient. PMID- 22306595 TI - Waking up to fatigue. PMID- 22306596 TI - Moving and handling in the community: update on legislation and best practice. AB - Over L 400 million per year is spent on back injuries to NHS staff, and back injuries are the largest single cause of work-related sickness in the UK health sector. Moving and handling is an integral part of practice in a community setting, and community nurses face unique challenges to ensure the safety of and minimize risk to both patients and themselves. As with any care activity, moving and handling needs have to be assessed, planned for, implemented and evaluated. This article explains the legislation related to moving and handling, with particular application to community nurses. It focuses on the Health and Safety Executive's (2009) advice Working Alone: Health and Safety Guidance on the Risks of Lone Working, which reinforced that employers have responsibility for the health, safety and welfare of all their employees while they are at work. Employers have a duty to assess risks to lone workers and take steps to avoid or control these risks. Employees have the responsibility to take reasonable care of themselves and others. This article also explores the assessment of the specific risks nurses in the community are confronted with and provides advice on addressing and minimizing these risks at work, both in the client's home and in health-care facilities. PMID- 22306597 TI - Managing constipation: a focus on care and treatment in the palliative setting. AB - Constipation can cause unnecessary discomfort and suffering for patients, and there appears to be a lack of awareness among nurses and doctors about its cause, impact and management. A large proportion of the evidence for the assessment and management of constipation in the context of palliative care is derived from the perspective of advanced cancer and from guidelines developed at a European level. Although constipation remains a problem for palliative care patients, early intervention combined with continuous and impeccable assessment can assist in its management and improve patient comfort at the end of life. PMID- 22306598 TI - Clinical challenges and ongoing role changes for primary health-care nurses. AB - OBJECTIVE: To investigate the perceptions of primary health-care nurses (PHNs) about clinical demands and future challenges. METHOD: Qualitative content analysis of open questions from a questionnaire. A total of 121 PHNs from health care districts in northern Sweden filled in a questionnaire during a mandatory educational day. RESULTS: Key issues that were raised included: defending the specific professional role of the PHNs; strengthening their self-governance and authority; and ensuring adequate care in the future through education that focuses more on nursing practice than on academic work. CONCLUSION: To ensure that the role of the PHN continues to develop, it is necessary to enable them to articulate, discuss, and evaluate their profession and to learn, in concrete forms, how to implement science in clinical practice. PMID- 22306599 TI - Reducing admissions for long-term conditions: is telehealth the answer? AB - In December 2011, the Department of Health (DH) released a bulletin on the early findings from the telehealth Whole System Demonstrator (WSD) sites. The WSD programme is the world's largest telehealth trial, involving 6191 patients and 238 GP practices at 3 UK sites. The study focused on three conditions; diabetes, COPD and coronary heart disease. At first sight, the outcomes are impressive - certainly good enough to warrant the announcement to be made by the Prime Minister, who fully endorsed telehealth and announced its potential to benefit 3 million patients per year. PMID- 22306600 TI - Uncovering the features of negotiation in developing the patient-nurse relationship. AB - This article describes a study that set out to explore the interaction between patients and nurses in community practice settings, in order to understand the social meanings and understandings brought to the interaction and at play within it. METHOD: The study used a grounded theory methodology with traditional procedures. Driven by constant comparative analysis, data were collected by non participant observation and informal and semi-structured interviews in four community health centres. Eighteen patients and 18 registered practice nurses participated. RESULTS: Negotiation was found to be a fundamental process in patient- nurse interaction. Navigation, socio-cultural characteristics and power and control were found to be key properties of negotiation. The negotiation processes for developing understanding required patients and nurses to draw upon social meanings and understandings generated from within and beyond their current interaction. CONCLUSION: Social meanings and understandings created within and beyond the health-care setting influence negotiation. The developmental nature of negotiation in interaction is an important dimension of the patient- nurse relationship in community practice. PMID- 22306601 TI - Nursing people at home is a special skill that requires support. AB - Nursing people at home has always been a special skill. It is very different from nursing people in hospital beds, or in clinical type settings outside of hospital, such as GP surgeries and health centres. The real point at which care changes fundamentally is when it crosses the patient's doorstep. To provide high quality nursing care to people in their own homes requires particular skills, knowledge and approaches - and the development of these has been seriously neglected in recent years. These are the basic tenets of the new report from the Queen's Nursing Institute (QNI) (2011), which was launched at the House of Lords in November 2011. The evidence for the report was gathered throughout the first year of the QNI's Right Nurse, Right Skills campaign, which was supported by BJCN. As part of the campaign, both nurses and members of the public were invited to leave stories and comments on a special webpage, and hundreds of people did so. The nurses talked about the replacement of registered nurses with health-care assistants, and the influx of inexperienced nurses who were not given the support they needed to develop community skills. Patients and carers spoke of their experiences of care - most of the time, these were good or excellent. However, too often, care was delivered by nurses or assistants who lacked the right skills to prevent harm or deliver care properly. The results were sometimes discomfort, sometimes unnecessary suffering, and occasionally very serious. PMID- 22306602 TI - Assessing children's competence to consent to treatment. AB - Although district nurses provide care and treatment to adults, they also have children on their caseloads from time-to-time. Obtaining consent for the examination and treatment of children is a complex process, where parental responsibility and the developmental concept of Gillick competence become increasingly intertwined as the child matures to adulthood. In this article, the authors consider the requirements for Gillick competence, and highlight the factors district nurses must consider when determining whether a child is competent to give consent to treatment. PMID- 22306604 TI - The client partnership. PMID- 22306605 TI - Metabolically induced heteroplasmy shifting and l-arginine treatment reduce the energetic defect in a neuronal-like model of MELAS. AB - The m.3243A>G variant in the mitochondrial tRNA(Leu(UUR)) gene is a common mitochondrial DNA (mtDNA) mutation. Phenotypic manifestations depend mainly on the heteroplasmy, i.e. the ratio of mutant to normal mtDNA copies. A high percentage of mutant mtDNA is associated with a severe, life-threatening neurological syndrome known as MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes). MELAS is described as a neurovascular disorder primarily affecting the brain and blood vessels, but the pathophysiology of the disease is poorly understood. We developed a series of cybrid cell lines at two different mutant loads: 70% and 100% in the nuclear background of a neuroblastoma cell line (SH-SY5Y). We investigated the impact of the mutation on the metabolism and mitochondrial respiratory chain activity of the cybrids. The m.3243A>G mitochondrial mutation induced a metabolic switch towards glycolysis in the neuronal cells and produced severe defects in respiratory chain assembly and activity. We used two strategies to compensate for the biochemical defects in the mutant cells: one consisted of lowering the glucose content in the culture medium, and the other involved the addition of l-arginine. The reduction of glucose significantly shifted the 100% mutant cells towards the wild-type, reaching a 90% mutant level and restoring respiratory chain complex assembly. The addition of l-arginine, a nitric oxide (NO) donor, improved complex I activity in the mutant cells in which the defective NO metabolism had led to a relative shortage of NO. Thus, metabolically induced heteroplasmy shifting and l-arginine therapy may constitute promising therapeutic strategies against MELAS. PMID- 22306606 TI - Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses. AB - Efforts to study the development and function of the human cerebral cortex in health and disease have been limited by the availability of model systems. Extrapolating from our understanding of rodent cortical development, we have developed a robust, multistep process for human cortical development from pluripotent stem cells: directed differentiation of human embryonic stem (ES) and induced pluripotent stem (iPS) cells to cortical stem and progenitor cells, followed by an extended period of cortical neurogenesis, neuronal terminal differentiation to acquire mature electrophysiological properties, and functional excitatory synaptic network formation. We found that induction of cortical neuroepithelial stem cells from human ES cells and human iPS cells was dependent on retinoid signaling. Furthermore, human ES cell and iPS cell differentiation to cerebral cortex recapitulated in vivo development to generate all classes of cortical projection neurons in a fixed temporal order. This system enables functional studies of human cerebral cortex development and the generation of individual-specific cortical networks ex vivo for disease modeling and therapeutic purposes. PMID- 22306607 TI - Autocrine/juxtaparacrine regulation of axon fasciculation by Slit-Robo signaling. AB - Axons travel to their targets in bundles or fascicles, but the molecules regulating fasciculation remain incompletely characterized. We found that Slit2 and its Robo receptors are expressed by motor axons, and that inactivation of Slit2 or Robo1 and Robo2 in mice caused axons to defasciculate prematurely at muscle targets. In vitro, Slit2 secreted by motoneurons regulated fasciculation through Robo1 and Robo2. These results support the idea that Slit2 promotes axon fasciculation via an autocrine and/or juxtaparacrine mechanism. PMID- 22306608 TI - A role for primary cilia in glutamatergic synaptic integration of adult-born neurons. AB - The sequential synaptic integration of adult-born neurons has been widely examined in rodents, but the mechanisms regulating the integration remain largely unknown. The primary cilium, a microtubule-based signaling center, is essential for vertebrate development, including the development of the CNS. We examined the assembly and function of the primary cilium in the synaptic integration of adult born mouse hippocampal neurons. Primary cilia were absent in young adult-born neurons, but assembled precisely at the stage when newborn neurons approach their final destination, further extend dendrites and form synapses with entorhinal cortical projections. Conditional deletion of cilia from adult-born neurons induced severe defects in dendritic refinement and synapse formation. Deletion of primary cilia led to enhanced Wnt and beta-catenin signaling, which may account for these developmental defects. Taken together, our findings identify the assembly of primary cilia as a critical regulatory event in the dendritic refinement and synaptic integration of adult-born neurons. PMID- 22306609 TI - Chronic heat treatment causes skin wrinkle formation and oxidative damage in hairless mice. AB - We have previously demonstrated that heat shock could induce expression of matrix metalloproteinases (MMPs) in skin cells. These results implicated that chronic heat treatment may cause skin wrinkles. Therefore, in the present study, we investigated the effects of chronic heat treatment (43 degrees C, 30 min, 3 times/week, 6 weeks) on wrinkle formation in skin of hairless mice. We found that repetitive heat treatment induced skin wrinkles after a period of 6 weeks in skin of hairless mice. Histologically, heat treatment resulted in increased thickness of the epidermis and dermis. And repetitive heat treatment resulted in significantly increased expression of MMP-13 protein and mRNA, but not MMP-2 and 9, in skin of hairless mice. We also demonstrated that activities of antioxidant enzymes, catalase, and superoxide dismutase (SOD), were reduced by chronic heat treatment. In addition, oxidative damage was increased in skin of mice after chronic exposure to heat shock. Taken together, our results suggested that chronic exposure of the skin to heat can cause skin wrinkling. And, increase of MMP-13, decrease of antioxidant enzymes activity, and consequent oxidative damage by chronic heat treatment may play an important role in development of skin aging in hairless mice. PMID- 22306610 TI - Aging alters folate homeostasis and DNA damage response in colon. AB - The risk for developing colorectal cancer increases exponentially with age. We demonstrate that spontaneous loss of folate in the colon results in DNA damage accumulation and aberrant DNA damage responses that may contribute to the increased genomic instability and cancer risk in colon. We find greater than 2 fold changes in the expression of folate-absorption and folate retention genes within the colonocyte, demonstrating that with age the colon is able to induce expression of appropriate genes in response to limiting folate status. However, we also find that aging results in spontaneous accumulation of uracil in colon DNA, indicating that folate status is not fully restored by the increase in folate absorption. Expression of uracil-excising enzymes (Ung and Smug) are induced in response to uracil accumulation, and with age we see an approximate 3 fold increase in the level of expression that is matched by a corresponding increase in DNA polymerase beta expression. In further evaluating the DNA damage response, we investigated p53 localization and function and find abundant p53 levels, with p53 sequestered almost entirely in the cytoplasm. To determine whether cytoplasmic localization might impact p53 transactivation function, we conducted an unbiased screen of p53-target genes and found that age substantially alters expression of p53-target genes. PMID- 22306611 TI - Comparative transcriptome analysis of Paracoccidioides brasiliensis during in vitro adhesion to type I collagen and fibronectin: identification of potential adhesins. AB - Paracoccidioidomycosis is caused by the dimorphic fungus Paracoccidioides brasiliensis. The extracellular matrix (ECM) plays an important role in regulation of cell adhesion, differentiation, migration and proliferation of cells. An in vitro binding assay of P. brasiliensis yeast cells adhering to type I collagen and fibronectin was performed in order to identify novel adhesins. Representational difference analysis (RDA) was employed to identify genes upregulated under adhesion-inducing conditions. Expressed sequence tags (ESTs) from cDNA libraries generated by the RDA technique were analyzed. Genes related to functional categories, such as metabolism, transcription, energy, protein synthesis and fate, cellular transport and biogenesis of cellular components were upregulated. Transcripts encoding the P. brasiliensis protein enolase (PbEno) and the high-affinity cooper transporter (PbCtr3) were identified and further characterized. The recombinant enolase (rPbEno) and a synthetic peptide designed for PbCtr3 were obtained and demonstrated to be able to bind ECM components. Immunofluorescence assays demonstrated that rPbEno specifically binds to the macrophage surface, reinforcing the role of this molecule in the P. brasiliensis interaction with host cells. In addition, upregulation of selected genes was demonstrated by qRT-PCR. In synthesis, the strategy can be useful in characterization of potential P. brasiliensis adhesins. PMID- 22306612 TI - Ischemic injury decreases parvalbumin expression in a middle cerebral artery occlusion animal model and glutamate-exposed HT22 cells. AB - Parvalbumin is a calcium-binding albumin protein that is involved in neuronal maturation, differentiation, axonal transport, and neurotransmitter release. Parvalbumin protects neuron from cell death through reduction of intracellular Ca2+ concentrations. In this study, we investigated parvalbumin expression after neuronal cell injury. Middle cerebral artery occlusions (MCAO) were surgically performed in a rat model to induce focal cerebral ischemic injury. Adult male rats were used and brain tissues were collected 24 h after MCAO. MCAO increases infarct damages and apoptotic cell death in cerebral cortex. A proteomic approach revealed a decrease of parvalbumin expression in MCAO-operated animals. RT-PCR and Western blot analyses showed that MCAO induces a reduction in parvalbumin transcript and protein levels, respectively. The numbers of parvalbumin-positive cells were also decreased in the cerebral cortices of MCAO-operated animals. Moreover, glutamate exposure significantly increased intracellular Ca2+ concentrations and induced a reduction of parvalbumin expression in a hippocampal derived cell line. These results suggest that the reduction in parvalbumin levels after ischemic brain injury can modulate neuronal cell death. PMID- 22306613 TI - The effects of neuregulin-1beta on neuronal phenotypes of primary cultured dorsal root ganglion neurons by activation of PI3K/Akt. AB - Neuregulin-1beta (NRG-1beta) signaling has multiple functions in neurons. NRG-1 signaling regulates neuronal development, migration, myelination, and synaptic maintenance. The neuropeptide- and neurofilament (NF)-immunoreactive (IR) neurons are two major phenotypical classes in dorsal root ganglion (DRG). Whether NRG 1beta influences DRG neuronal phenotypes remains unknown. To assess the effects of NRG-1beta on DRG neuronal phenotypes, dissociated embryonic rat DRG neuronal culture model was established. Primary cultured DRG neurons were exposed to NRG 1beta (5nmol/L), NRG-1beta (10nmol/L), NRG-1beta (20nmol/L), NRG-1beta (20nmol/L) plus LY294002 (10MUmol/L) for 3 days, respectively. The DRG neurons were continuously exposed to growth media as control. After that, all above cultured DRG neurons were processed for double fluorescent labeling of calcitonin gene related peptide (CGRP) or neurofilament-200 (NF-200) and microtubule associated protein 2 (MAP2). The percentage of CGRP-IR neurons and NF-200-IR neurons was counted. The expression of CGRP mRNA and NF-200 mRNA was analyzed by real time PCR analysis. The percentage of CGRP-IR neurons but not NF-200-IR neurons increased significantly in the presence of NRG-1beta as compared with that in the absence of NRG-1beta. The levels of CGRP mRNA but not NF-200 mRNA increased significantly in the presence of NRG-1beta as compared with that in the absence of NRG-1beta. PI3K inhibitor LY294002 blocked the effects of NRG-1beta. These results support an important role for exogenous NRG-1beta in induction of the distinct neuronal phenotype response by activation of PI3K/Akt in sensory neurons. PMID- 22306614 TI - Translating stem cell therapies to the clinic. AB - One of the most remarkable advances in translational neuroscience of the last few years has been the emergence of cell-based approaches for a wide range of neurological disease and injuries. Molecular approaches designed for the treatment of neurological injuries and insults such as stroke, spinal cord injury and multiple sclerosis have proven to be of limited effectiveness in large part because it has become clear that there is not a single "magic bullet" that allows for neuronal survival, axonal regeneration and/or remyelination. Rather the pathogenesis of insults such as stroke, spinal cord injury and MS are complex, engaging multiple cell types and signaling pathways and as a result require the simultaneous intervention in multiple arenas in order to facilitate functional recovery. Cell therapies, because of their inherent complexity offer the opportunity to intervene at several points in the pathological process and thus may provide a more effective treatment strategy. Among the multiple cell types assessed as therapeutic treatment for neural insults, stem cells have emerged as possibly the most effective class. The particular characteristics of stem cells, namely their ability to self-renew and generate multiple cell types promoted their use as sources of cell replacement in the injured CNS. It is likely, however that the major advance that stem cells have over more restricted cell types is their ability to modulate the responses of the immune system and to influence endogenous tissue stem cells to accentuate repair. While preclinical studies are moving extremely rapidly, the effective translation of these studies to the clinical arena remains extremely challenging. PMID- 22306615 TI - Do levels of brain-derived neurotrophic factor (BDNF) in plasma correlate with psychopathology in healthy subjects? AB - In humans, it is widely accepted that brain-derived neurotrophic factor (BDNF) participates in the psychophysiology of psychiatric disorders. Yet the relationship between BDNF levels and psychopathological traits in the general population has not been examined. To test whether BDNF blood levels are associated with the modulation of psychopathological traits in healthy subjects, we assessed the correlation between BDNF serum and plasma levels measured at 9am and psychometric parameters using the symptom checklist 90 revised (SCL-90R) and temperament and character inventory (TCI). One hundred ten volunteers (67 male, 43 female, age: 35.5+/-8.3 (19-55)) were recruited for this study by advertisement in the Ulsan University Hospital. Among the SCL-90R scores, we found negative relationships between the natural log of BDNF plasma levels at 9am and the SCL-90R scores for somatization, obsessive-compulsiveness, interpersonal sensitivity, depression, anxiety, paranoid ideation, global severity index, and positive symptom total (p<0.05). However, TCI scores had no relationship with BDNF levels. It would be premature to conclude that low plasma BDNF level is associated with these psychopathological traits until the results are replicated with a larger sample. PMID- 22306616 TI - Comparative high-throughput RNAi screening methodologies in C. elegans and mammalian cells. AB - The discovery of RNAi in Caenorhabditis elegans has generated a paradigm shift in how research is performed. Targeted gene knockdown using high throughput screening approaches is becoming a routine feature of the scientific landscape, and researchers can now evaluate the function of each gene in the genome in a relatively short period of time. This review compares and contrasts high throughput screening methodologies in C. elegans and mammalian cells and highlights the breadth of applications of this technology. PMID- 22306617 TI - Epicardial ganglionated plexus stimulation decreases postoperative inflammatory response in humans. AB - BACKGROUND: Surgical cardiac revascularization produces a high degree of systemic inflammation and the secretion of several cytokines. Intensive postoperative inflammation may increase the incidence of postoperative atrial fibrillation and favor organ dysfunctions. No data documenting the anti-inflammatory properties of epicardial vagal ganglionated plexus stimulation are available. OBJECTIVE: To verify the feasibility and safety of postoperative inferior vena cava-inferior atrial ganglionated plexus (IVC-IAGP) burst stimulation and the effectiveness of this approach in reducing serum levels of inflammatory cytokines. METHODS: In 27 patients who were candidates for off-pump surgical revascularization, the IVC IAGP was located during surgery, a temporary wire was inserted, and a negative atrioventricular node dromotropic effect was obtained in 20 patients on applying high-frequency burst stimulation. In 5 patients atrial fibrillation or phrenic nerve stimulation was induced, and the remaining 15 patients served as the experimental group. Twenty additional patients underwent off-pump surgical revascularization without IVC-IAGP stimulation and served as the control group. On arrival in the intensive care unit, the experimental group underwent IVC-IAGP stimulation for 6 hours. Blood samples were collected at different times. RESULTS: The serum levels of cytokines were not statistically different at baseline and on arrival in the intensive care unit between the groups, while they proved statistically different after 6 hours of stimulation: interleukin-6 (EG: 121 +/- 71 pg/mL vs CG: 280 +/- 194 pg/mL; P = .004), tumor necrosis factor-alpha (EG: 2.68 +/- 1.81 pg/mL vs CG: 5.87 +/- 3.48 pg/mL; P = .003), vascular endothelial growth factor (EG: 93 +/- 43 pg/mL vs CG: 177 +/- 86 pg/mL; P = .002), and epidermal growth factor (EG: 79 +/- 48 pg/mL vs CG: 138 +/- 76 pg/mL; P = .012). CONCLUSIONS: Prolonged burst IVC-IAGP stimulation after surgical revascularization appears to be feasible and safe and significantly reduces inflammatory cytokines in the postoperative period. PMID- 22306618 TI - Ablation of ventricular arrhythmias arising near the anterior epicardial veins from the left sinus of Valsalva region: ECG features, anatomic distance, and outcome. AB - BACKGROUND: Left ventricular outflow tract tachycardia/premature depolarizations (VT/VPDs) arising near the anterior epicardial veins may be difficult to eliminate through the coronary venous system. OBJECTIVE: To describe the characteristics of an alternative successful ablation strategy targeting the left sinus of Valsalva (LSV) and/or the adjacent left ventricular (LV) endocardium. METHODS: Of 276 patients undergoing mapping/ablation for outflow tract VT/VPDs, 16 consecutive patients (8 men; mean age 52 +/- 17 years) had an ablation attempt from the LSV and/or the adjacent LV endocardium for VT/VPDs mapped marginally closer to the distal great cardiac vein (GCV) or anterior interventricular vein (AIV). RESULTS: Successful ablation was achieved in 9 of the 16 patients (56%) targeting the LSV (5 patients), adjacent LV endocardium (2 patients), or both (2 patients). The R-wave amplitude ratio in lead III/II and the Q-wave amplitude ratio in aVL/aVR were smaller in the successful group (1.05 +/- 0.13 vs 1.34 +/- 0.37 and 1.24 +/- 0.42 vs 2.15 +/- 1.05, respectively; P = .043 for both). The anatomical distance from the earliest GCV/AIV site to the closest point in the LSV region was shorter for the successful group (11.0 +/- 6.5 mm vs 20.4 +/- 12.1 mm; P = .048). A Q-wave ratio of <1.45 in aVL/aVR and an anatomical distance of <13.5 mm had sensitivity and specificity of 89%, 75% and 78%, 64%, respectively, for the identification of successful ablation. CONCLUSIONS: VT/VPDs originating near the GCV/AIV can be ablated from the LSV/adjacent LV endocardium. A Q-wave ratio of <1.45 in aVL/aVR and a close anatomical distance of <13.5 mm help identify appropriate candidates. PMID- 22306619 TI - Measuring changes after multidisciplinary rehabilitation of obese individuals. AB - BACKGROUND: In 2009, the Italian Society of Obesity developed the short-form questionnaire for Obesity-related Disabilities (TSD-OC). AIMS: To stage the degree of disability in obese patients using TSD-OC; to verify its sensitivity to change after rehabilitation. SUBJECTS: Three hundred and fifty-five adult obese individuals [body mass index (BMI) >30 kg/m2] undergoing rehabilitation. Exclusion criteria were severe cardiovascular or respiratory diseases, neurological and psychological conditions. Sensitivity to change of TSD-OC was evaluated in 194 patients out of the initial sample. METHODS: To define the disability levels according to TSD-OC, the method of interquartile range was applied to the initial sample. The 194 in-patients were assessed with Roland Morris Disability Questionnaire, Functional Independence Measure (FIM), Functional Visual Analogue Scale, and TSD-OC before (S0) and after 4 weeks (S1) of intensive (3 h daily) rehabilitation multidisciplinary program. Individuals were grouped according to age (1: age 30-59 yr; 2: age over 60 yr) and degree of obesity (BMI: A, 30-40 kg/m2; B, 40-50 kg/m2). RESULTS: At S1, BMI and all the clinical scores improved significantly in the whole study sample. The younger individuals with higher level of obesity showed a higher functional improvement ( 51.3%). In the older subjects, improvement was not statistically different when varying BMI (A2 -13.7% vs B2 -14.6%). In the whole group, the TSD-OC improvement was statistically greater than the physical FIM gain (-25.9% vs +5.4%, p<0.05). CONCLUSIONS: Our data evidenced that the TSD-OC is a sensitive measure of short term changes in disability status of obese individuals after rehabilitation. PMID- 22306620 TI - Comparative potency approach based on H2AX assay for estimating the genotoxicity of polycyclic aromatic hydrocarbons. AB - Polycyclic Aromatic Hydrocarbons (PAHs) constitute a family of over one hundred compounds and can generally be found in complex mixtures. PAHs metabolites cause DNA damage which can lead to the development of carcinogenesis. Toxicity assessment of PAH complex mixtures is currently expressed in terms of toxic equivalents, based on Toxicity Equivalent Factors (TEFs). However, the definition of new TEFs for a large number of PAH could overcome some limitations of the current method and improve cancer risk assessment. The current investigation aimed at deriving the relative potency factors of PAHs, based on their genotoxic effect measured in vitro and analyzed with mathematical models. For this purpose, we used a new genotoxic assay (gammaH2AX) with two human cell lines (HepG2 and LS 174T) to analyze the genotoxic properties of 13 selected PAHs at low doses after 24h treatment. The dose-response for genotoxic effects was modeled with a Hill model; equivalency between PAHs at low dose was assessed by applying constraints to the model parameters. In the two cell lines tested, we observed a clear dose response for genotoxic effects for 11 tested compounds. LS-174T was on average ten times more sensitive than HepG2 towards PAHs regarding genotoxicity. We developed new TEFs, which we named Genotoxic Equivalent Factor (GEF). Calculated GEF for the tested PAHs were generally higher than the TEF usually used. Our study proposed a new in vitro based method for the establishment of relevant TEFs for PAHs to improve cancer risk assessment. PMID- 22306621 TI - Monoclonal antibodies reveal multiple forms of expression of human microsomal epoxide hydrolase. AB - In a previous study, we developed five kinds of monoclonal antibodies against different portions of human mEH: three, anti-N-terminal; one, anti-C-terminal; one, anti-conformational epitope. Using them, we stained the intact and the permeabilized human cells of various kinds and performed flow cytometric analysis. Primary hepatocytes and peripheral blood mononuclear cells (PBMC) showed remarkable differences. On the surface, hepatocytes exhibited 4 out of 5 epitopes whereas PBMC did not show any of the epitopes. mEH was detected inside both cell types, but the most prominent expression was observed for the conformational epitope in the hepatocytes and the two N-terminal epitopes in PBMC. These differences were also observed between hepatocyte-derived cell lines and mononuclear cell-derived cell lines. In addition, among each group, there were several differences which may be related to the cultivation, the degree of differentiation, or the original cell subsets. We also noted that two glioblastoma cell lines reveal marked expression of the conformational epitope on the surface which seemed to correlate with the brain tumor-associated antigen reported elsewhere. Several cell lines also underwent selective permeabilization before flow cytometric analysis, and we noticed that the topological orientation of mEH on the ER membrane in those cells was in accordance with the previous report. However, the orientation on the cell surface was inconsistent with the report and had a great variation between the cells. These findings show the multiple mode of expression of mEH which may be possibly related to the multiple roles that mEH plays in different cells. PMID- 22306622 TI - Using independent component analysis to remove artifacts in visual cortex responses elicited by electrical stimulation of the optic nerve. AB - In visual prosthesis research, electrically evoked potentials (EEPs) can be elicited by one or more biphasic current pulses delivered to the optic nerve (ON) through penetrating electrodes. Multi-channel EEPs recorded from the visual cortex usually contain large stimulus artifacts caused by instantaneous electrotonic current spread through the brain tissue. These stimulus artifacts contaminate the EEP waveform and often make subsequent analysis of the underlying neural responses difficult. This is particularly serious when investigating EEPs in response to electrical stimulation with long duration and multi-pulses. We applied independent component analysis (ICA) to remove these electrical stimulation-induced artifacts during the development of a visual prosthesis. Multi-channel signals were recorded from visual cortices of five rabbits in response to ON electrical stimulation with various stimulus parameters. ON action potentials were then blocked by lidocaine in order to acquire cortical potentials only including stimulus artifacts. Correlation analysis of reconstructed artifacts by ICA and artifacts recorded after blocking the ON indicates successful removal of artifacts from electrical stimulation by the ICA method. This technique has potential applications in studies designed to optimize the electrical stimulation parameters used by visual prostheses. PMID- 22306623 TI - How additional visual feedback of the movements between center of pressure and vertically projected center of gravity can be used by hemiparetic patients. AB - PURPOSE: In healthy adults, the beneficial effect of providing additional visual feedback (VFB) with a delay of either the center of pressure (CP) or the difference between CP movements and center of gravity (CP-CGv) movements was previously demonstrated and explained by their capacity to decrease their CP-CGv movements. The present study seeks to demonstrate whether similar trends could be observed in hemiparetic patients. METHODS: Posturographic measurements were recorded in 56 hemiparetic patients in 3 VFB conditions: (1) CP in real time (VFBCP0), (2) CP with a 600-ms delay (VFBCP600), and (3) CP-CGv with a 600-ms delay (VFBCP-CG600). A condition without VFB (eyes open [EO]) was also included. The individual capacity to lower CP-CGv movements as compared to the reference VFBCP0 condition was assessed using dependency coefficients (ie, average surface covered by the CP-CGv displacements in an experimental condition relative to the VFBCP0 condition) in the VFBCP600, VFBCP-CG600, and EO conditions. RESULTS: Reduced CP-CGv movements were only obtained for half of the patients for the conditions with delay or without VFB. Significant linear correlations revealed that the most successful patients are characterized by reduced CP-CGv movements in these conditions and in the EO condition. In contrast, a poor correlation was found with the patients' clinical scores. CONCLUSION: Based on the behavioral profile of a patient able to use these VFB techniques effectively, this study emphasizes the complementary nature of the various conditions proposed by the VFB technique and provides insights for establishing rehabilitation protocols based on this VFB technique. PMID- 22306624 TI - Practicability and sensitivity to change of the activities-specific balance confidence scale and 12-item Walking Scale for stroke. AB - PURPOSE: To investigate the practicability and sensitivity to change of the Activities-specific Balance Confidence Scale (ABC) and the 12-item Walking Scale (WS-12) in persons at different phases after stroke. METHOD: A longitudinal data collection with repeated measurements at 0 to 14 days and 3 months post stroke combined with a cross-sectional approach for persons more than 1 year post stroke. The participants were 37 persons (median age, 79 years; interquartile range [IQR] 67-86) in the acute phase admitted to the University Hospital of Orebro (sample A) of whom 31 were measured at follow-up, and 67 persons at 4 primary care centers in Orebro County Council (median age, 68 years; IQR, 61-76) who were more than 1 year post stroke (sample B). RESULTS: The ABC registered balance confidence during activities and the WS-12 measured walking limitations as perceived by participants. The observed score range per item and for the total scores covered a wide range with no floor or ceiling effects. For the older persons in sample A, 3 ABC items requiring high balance levels were found difficult even before stroke. The item for running in the WS-12 was also often commented on as being not possible before stroke. The ABC showed moderate ability and the WS-12 showed good ability to measure change. CONCLUSION: The scales are practical to use and sensitive to change for persons with remaining walking ability at different phases post stroke. PMID- 22306625 TI - Effects of weight-shift training on balance control and weight distribution in chronic stroke: a pilot study. AB - PURPOSE: The objective was to evaluate the effect of weight-shift training on functional balance, weight distribution, and postural control measures during standing and forward reach tasks in subjects with chronic stroke. METHODS: Nine male subjects (mean age, 66 years; range, 60-75 years) who experienced a stroke 3 to 13 years previously participated in a 4-week training program consisting of static and dynamic balance exercises with visual feedback and gait training with wall support. Balance control was assessed before and after the intervention with clinical measures (Berg Balance Scale) and with a pressure platform for registering the center of pressure (CoP) during quiet stance (weight distribution, CoP sway area, and velocity), and during a forward reach task at shoulder and knee levels. Intervention effects were evaluated with the Wilcoxon matched-pairs test. RESULTS: After training, the group improved their Berg Balance Scale median score from 42 (range, 14-54) to 46 (20-55) (P = .01), CoP sway area [10.6 (5.0-31.4) to 3.0 (1.8-10.8) cm2; P = .01], and mean velocity [3.5 (2.4-8.0) to 1.7 (0.9-3.7) mm/s; P = .01] during quiet standing but not weight distribution (P = .59). During the forward reach tasks, most of the postural control measures such as movement time, CoP displacement, and CoP velocity were significantly (P < .05) improved after the training period for both the affected and nonaffected sides as compared to before the training period. CONCLUSION: A weight-shift training program improved balance control but not weight distribution in a group of chronic stroke subjects. Larger, randomized, and controlled studies are necessary. PMID- 22306626 TI - Poststroke fatigue: does group education make a difference? A randomized pilot trial. AB - PURPOSE: Fatigue is common and contributes to poor stroke outcomes. Educational fatigue management reduces fatigue in other conditions (eg, cancer). There was no evidence for educational fatigue management in stroke patients. This trial evaluated an educational fatigue management intervention in stroke survivors. METHODS: Participants in this pilot trial were 19 individuals 3 to 18 months post incident stroke who experienced fatigue (Fatigue Severity Scale (FSS) ?3.9). Participants were allocated to a Fatigue Management Group (FMG) or General Stroke Education (GSE) control group. Assessment occurred pre and post intervention and at the 3-month follow-up. The primary outcome was FSS fatigue. RESULTS: Both groups had significantly reduced FSS fatigue from baseline to postintervention assessment. Though not significantly different (P ?.05), FSS decreased more in FMG participants than controls. Participant SF-36 social functioning and Hospital Anxiety Depression Scale depression scores improved significantly, but the groups did not differ significantly (P ?.05). CONCLUSIONS: The findings indicate that the FMG intervention is both feasible and should be the subject of a full trial. PMID- 22306627 TI - Success of recommending oral diets in acute stroke patients based on passing a 90 cc water swallow challenge protocol. AB - PURPOSE: This study investigated the success of recommending specific oral diets following an acute stroke based on passing a 90-cc water swallow challenge protocol. METHOD: The study was a single group consecutively referred case series design. The study took place in a large, urban, tertiary care teaching hospital and involved 75 acute adult stroke inpatients in a 90-cc water swallow challenge. The volume (in cc) of liquid ingested, percent of meal eaten, and specific diet recommendations made 12 to 24 hours after passing a 90-cc water swallow challenge were accessed electronically from routine oral intake information entered by nursing staff on each participant's daily flow sheets. Nurses were blinded to the study's purpose. RESULTS: All 75 participants were drinking thin liquids and eating food successfully 12 to 24 hours after passing a 90-cc water swallow challenge. The mean volume of liquid ingested was 385.4 cc and percent of diet eaten ranged from 10% to 100%. Flow sheets indicated that specific diet recommendations were followed with 100% accuracy. CONCLUSIONS: Successfully recommending specific oral diets to acute stroke patients based on passing a 90 cc water swallow challenge protocol was supported. A 90-cc challenge is an easily administered, highly reliable, cost-effective, and validated clinical assessment that can be used by a variety of qualified health care professionals to identify aspiration risk. When a 90-cc challenge protocol is passed, specific diet recommendations can be made safely and confidently without the need for further objective dysphagia testing. PMID- 22306628 TI - Subjective evaluation of sleep apnea is not sufficient in stroke rehabilitation. AB - OBJECTIVE: Sleep apnea (SA) is common in stroke patients and is associated with poor functional outcome. Therefore, we studied the clinical value of the Berlin Questionnaire (BQ), a subjective screening method to detect stroke patients with SA in a neurorehabilitation care unit, and compared it with respirographic sleep studies. Another aim was to explore the association of SA with functional status in the subacute phase after stroke. METHODS: Sixty-eight stroke patients were subjected to respirographic sleep studies to determine their apnea-hypopnea index (AHI). Subjective evaluation was performed by means of the BQ. Functional outcome was assessed by the Barthel Index (BI). Sensitivity and specificity of the BQ for detecting SA in stroke patients were calculated. RESULTS: Respirographic sleep studies showed a high prevalence of moderate and severe sleep apnea in 56% of stroke patients. Sensitivity and specificity of the BQ for SA (AHI ? 15) were 0.69 and 0.15, respectively. The area under the receiver operating characteristics (ROC) curve for detection of SA was 0.58. The AHI correlated significantly with the BI (r = -0.57, P <= .001). CONCLUSION: As the BQ demonstrated low diagnostic utility in stroke rehabilitation, screening for SA should not be based solely on clinical interviews. SA is linked to poor functional status in the subacute phase post stroke. PMID- 22306629 TI - The factor structure of the center for epidemiologic studies depression scale in stroke patients. AB - PURPOSE: The purpose of this study is to investigate the factor structure of the Center for Epidemiologic Studies Depression (CES-D) scale in community-residing stroke patients. METHODS: The sample for this study was a convenience sample of 203 persons who had experienced strokes and were in a convalescent center for the disabled and a primary care unit in Korea. Data were collected through a questionnaire that included the CES-D scale. Cognitive function was assessed by the validated Korean version of the Mini-Mental State Examination (MMSE-K). The structure of the CES-D scale was analyzed by exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) using SPSS 17.0 and Amos 7.0. The reliability of the CES-D scale was assessed by calculating the internal consistency of Cronbach's alpha. RESULTS: The 1-, 3-, and 4-factor models did not show the adequate fit indices. Two competing factor models were tested by CFA for the entire sample after identifying the factor structure using EFA. The 5-factor structure (loss of vitality, positive affect, psychomotor retardation, negative affect, and interpersonal problems) supported and explained 61.25% of the variance. CONCLUSIONS: The results of this study suggest that the CES-D scale is a useful depressive symptom screening tool for community-residing stroke patients. Identifying the psychometric properties of the CES-D scale would help health professionals to understand the comprehensive assessment of community residing stroke patients. PMID- 22306630 TI - Community re-engagement and interprofessional education: the impact on health care providers and persons living with stroke. AB - PURPOSE: This study evaluated the impact of an educational intervention that integrates concepts of a community re-engagement framework (CR) and interprofessional collaboration (IPC) on health care providers' (HCP) practice with persons living with stroke (PLS). METHOD: A mixed-methods design was used in which HCPs (n = 67) and PLS (n = 29) participated from 9 organizations across the care continuum. Pre- and postintervention surveys and interviews were conducted with the HCPs. One-on-one interviews with stroke clients were also conducted pre and post intervention. Quantitative responses were analyzed in SPSS (Chicago, Illinois, USA) for descriptive frequencies and differences between pre- and postintervention groups. Qualitative open-ended responses were thematically coded using NVivo7. RESULTS: Significant increases occurred in HCPs' knowledge of CR, confidence levels in working with PLS, enhanced understanding of the complex needs of PLS, and positive self-reported impacts on practice. PLS reported positive perceptions of care pre and post intervention. CONCLUSIONS: The intervention provided HCPs with a common language and framework to work collaboratively and holistically in delivering care consistent with stroke best practices. PMID- 22306631 TI - Assessment of fluctuating decision-making capacity in individuals with communication barriers: a case study. AB - A current need exists for research to assist clinicians in the capacity evaluation process, especially in relation to assessment of clients with complex issues such as fluctuating capacity and communication barriers. The aim of this article is to promote knowledge and consideration of these issues through an examination of neuropsychological, ethical, and medical-legal factors associated with the assessment of capacity in an individual with both fluctuating capacity and communication impairments. The discussion includes a narrative case study of a complex individual case seen by the Regional Capacity Assessment Team (RCAT) for an assessment of decision-making capacity related to personal and financial matters. Relevant background information about this client, behavioral observations, neuropsychological test results, and the process and outcome of the RCAT targeted capacity interview are presented. Based on previous literature and the case study, a series of recommendations are provided to guide the clinician through the capacity evaluation process with individuals with complex issues. Common pitfalls, nuances, and dilemmas involved in capacity assessment are addressed. PMID- 22306632 TI - Ethical issues in inpatient rehabilitation length of stay determination. AB - The intersection of financial considerations and patient care is fraught with conflicts of interest and, frequently, with accompanying ethical dilemmas. Inpatient rehabilitation is a unique component of the health care delivery system and presents a distinctive set of ethical dilemmas, including issues of patient autonomy and decision making. This article focuses on the particular issue of resource allocation and the determination of inpatient rehabilitation hospital length of stay. The challenges posed by uncertain endpoints as goals of rehabilitative care and the psychological aspects of recovery from major disabling illness are among the issues confronted by health care providers in the rehabilitation setting when they try to balance patient and institutional goals. PMID- 22306633 TI - The code within the context of regulatory transparency. PMID- 22306634 TI - Renal replacement therapy: how far have we come? PMID- 22306635 TI - Acute leukaemia: making sense of a complex blood cancer. AB - Acute leukaemia represents a diverse group of blood cancers that affect both children and adults. Treatment schedules for these haematology cancers are often prolonged, with many associated side effects and complications. Nurses caring for patients with acute leukaemia require an anticipatory approach, where care is aimed at minimizing the side effects of treatment and being constantly vigilant for any impending adverse effects. Moreover, patients require support for the psychosocial issues that can arise for patients during their illness. This article provides an overview of acute lymphoblastic leukaemia and acute myeloid leukaemia. Nursing considerations in the care of patients being treated for acute leukaemia are also explored. PMID- 22306636 TI - Management of faecal incontinence in graft-versus-host disease. AB - Graft-versus-host disease (GvHD), a common yet serious complication of allogeneic haemopoietic stem cell transplantation, can cause significant morbidity and negatively impact on patients' quality of life. The gastrointestinal tract is frequently affected resulting in nausea and vomiting, abdominal pain and profuse diarrhoea (Washington and Jagasia, 2009) which can be both distressing and humiliating for patients. The volume of watery, green diarrhoea produced can be greater than 2 litres per day (Ferrara et al, 2009) and is one indicator of the severity of GvHD. It may, in some cases, lead to faecal incontinence. Management of GvHD-associated diarrhoea involves the use of high-dose steroids to control the exaggerated immune response, anti-diarrhoeal medication, management of fluid and electrolytes, and nutritional management. It may also require management of faecal incontinence and prevention of incontinence-associated dermatitis. This paper describes the pathology of GvHD, the management of GvHD-associated diarrhoea and faecal incontinence and discusses the potential use of a faecal management system inappropriately selected individuals with uncontrolled diarrhoea and limited mobility. PMID- 22306637 TI - Managing the acutely ill adult with sickle cell disease. AB - Sickle cell disease (SCD) is an autosomal recessively inherited condition, affecting the structure of the haemoglobin. SCD is a long-term chronic condition which is manifested by periods of acute painful sickling crisis, known as vaso occlusive crisis (VOC) and is the cause of 90% of sickle cell-related hospital admissions. SCD is one of the most common genetic conditions worldwide and in the UK there are approximately 12,500 people living with it (Streetly et al,1997; Howard et al, 2008), making it more common than cystic fibrosis, yet there still remains many challenges in managing these patients when they become acutely ill. Lack of awareness and understanding of the illness, concerns regarding addiction and limited attention to the psycho-social implications of the illness, leads to less than effective care for this patient group when they are hospitalized. The aims of this article are to outline the pathophysiology of SCD, identify the causes of VOC and discuss the key principles of nursing management for patients experiencing a VOC. PMID- 22306638 TI - Heart to heart: a programme for children on a cardiac ward. AB - This paper presents three research case studies of children who have had surgery for a cardiac condition and discusses the experiences of the children and their families through their responses to the Heart Beads programme, as well as the insights gained by staff. The Children's Hospital at Westmead has a significant population of children with cardiac conditions. For many of these, diagnosis signals the beginning of a long, arduous journey with multiple procedures and admissions. The hospital has a family-centred care focus, and the cardiac ward undertook a project to implement and progress changes consistent with this approach. Staff developed the Heart Beads programme to enhance the care of children being treated for cardiac conditions. The programme involves children receiving distinct beads specific to each cardiac procedure, treatment, or event in recognition of their experience. A total of 7 staff members and 11 families were interviewed and particular stories were noted by staff. The case studies presented illustrated how nursing staff were able to recognize potential improvements to care and acknowledge the experiences of patients and families. Assumptions questioned as a result of the programme related to the complexity of the child's condition and gender. The death of a child and the acknowledgement of the child's life is also considered. Heart Beads allowed staff to reflect on the positive aspects of the care they provided. PMID- 22306639 TI - Pneumonia part 1: Pathology, presentation and prevention. AB - Pneumonia is a significant cause of morbidity and mortality and can affect all age groups although it is the very young and the very old who are most at risk. Pneumonia can be caused by many different organisms and can present as a primary condition or as a complication of other diseases or acute health problems. This article will give an overview of the disease, its symptoms and treatment and will focus primarily on community-acquired pneumonia. Two further articles will look at specific causative organisms, i.e. Streptococcus Pneumoniae and influenza, as well as the preventive strategies for these. PMID- 22306640 TI - A liquid-film forming acrylate cream for the treatment of anal pruritus. AB - Pruritus ani is a hidden but frequently occurring clinical condition, with a large impact on patients' quality of life. Currently, therapeutic options are scarce, offering mainly limited success. The authors performed a prospective, open-label, two-centre pilot study to analyse the efficacy and safety of a liquid film forming acrylate cream for the treatment of pruritus ani and peri-anal skin irritation. A total of 28 patients were included and applied the cream to the cleansed anal and peri-anal skin once daily for a study period of 3-4 weeks. The primary outcome measure was the reduction of pruritis ani, comparing day 0 to day 28 results. For this purpose, a visual analog scale (VAS) was used. Secondary parameters included the physician global assessment score (PGA) of peri-anal skin condition, assessment of patients' quality of life using a specifically designed quality of life scoring tool, and patient satisfaction with the treatment regimen. The application of the acrylate skin protection cream resulted in a fast and substantial improvement of all study parameters, with a high score for patient satisfaction. The cream was well tolerated without any adverse events noted during the study period. The authors' pilot study has generated initial evidence that the acrylate skin protection cream may be effective for the treatment of pruritus ani. However, further randomized controlled studies are needed to confirm the authors' findings. PMID- 22306641 TI - The benefits of a ward simulation exercise as a learning experience. AB - This article describes the findings from a pilot study undertaken to identify the potential benefits of a ward simulation exercise in developing the capabilities of newly qualified nurses. Eight newly qualified nurses were recruited to participate in this pilot study which was based in the Clinical Skills Centre, Ninewells Hospital, Dundee. This pilot study was performed in conjunction with NHS Tayside Practice Education Facilitators and the University of Dundee. Data collection methods involved reflective learning logs which were reviewed independently by an expert group of teachers and practitioners. A focus group session was also undertaken to understand the lived experience of the newly qualified nurse during the ward simulation exercise. Core themes (listed in order of importance) related to the professional development of newly qualified nurses that were identified through this pilot study were: an increase in confidence, development of stress management skills, improved management of the acutely unwell patient, the transfer of skills learnt in simulation to the clinical setting, development of communication skills and reflection skills. Participants in this pilot study demonstrated increased levels of confidence in their communication skills, their ability to prioritize care and to engage in collaborative teamworking. PMID- 22306642 TI - Toppling the Bill--pass it on. PMID- 22306643 TI - The NMC's adaptation framework for European nurses. PMID- 22306644 TI - Reforming the law concerning assisted dying. AB - The question of whether English law should be reformed to legalize assisted dying has been the cause of heated debate over many years. The courts have consistently rejected challenges to change the law in the area. However in 2009 Debbie Purdy achieved success in requiring the Director of Public Prosecutions to produce prosecution guidelines on assisted suicide. This paper explores the current law in the area and examines the proposals for reform of the Falconer Commission which were published in January 2012. PMID- 22306645 TI - The social determinants of health and the patient safety paradigm. AB - This article extends the thesis presented in the paper by Tingle, Gibson and Ferrante (2011) that the patient safety agenda needs to operate within a new paradigm. We will introduce the social determinants of health (SDH) as an emerging discourse in global public health. The SDH advocate social and health equity among nations and individuals, and within countries and communities. It has become a key driver for policy makers, health researchers and public health professionals (Raphael, 2011). This article will demonstrate that the paradigmatic lens of SDH offers the opportunity to develop a more upstream analysis of the patient safety agenda based on health systems. PMID- 22306646 TI - Professional development: from staff nurse to nurse consultant. Part 4: Keeping up to date. PMID- 22306647 TI - Public opinion and political resolve. PMID- 22306648 TI - Lipophilic and electrostatic forces encoded in IAM-HPLC indexes of basic drugs: their role in membrane partition and their relationships with BBB passage data. AB - The membrane phospholipid affinity data, log k(w)(IAM), for 14 basic drugs spanning a wide lipophilicity range were measured by HPLC on two different phospholipid stationary phases, i.e. IAM.PC.MG and IAM.PC.DD2. These data related weakly with log P(N) values, the n-octanol/water partition coefficients of the neutral forms; poorer relationships were found with log D(7.0) values, the n octanol/water partition coefficients of the mixtures of neutral and ionized forms at pH 7.0. The lack of collinearity confirms that, differently from partition in n-octanol/water, partition in phospholipids encodes not only lipophilic/hydrophobic intermolecular recognition forces but also ionic bonds, due to electrostatic interactions between electrically charged species and phospholipids, according to the "pH-piston hypothesis". This component of interaction was parameterized by Delta log k(w)(IAM) values; they are the differences between the log k(w)(IAM) values experimentally measured and the values expected for neutral isolipophilic compounds. Delta log k(w)(IAM) values of the various analytes changed almost linearly from positive to negative values at increasing lipophilicity. This behavior is consistent with an interaction mechanism with membrane phospholipids including two intermolecular interaction forces: (i) lipophilic/hydrophobic interactions, which decrease on ionization proportionally to the lipophilicity of the neutral forms, and (ii) electrostatic interactions, which increase on ionization and are quite constant for all the analytes at a given ionization degree. Since BBB passage of the considered compounds is supposed to be based on passive mechanisms, we investigated the possible relationships between log BB values, i.e. the logarithms of the ratio between brain and blood concentrations, and three physico-chemical parameters, i.e. (i) log P(N) (lipophilic interaction of the neutral form), (ii) log k(w)(IAM) (global interaction with phospholipids), and (iii) Delta log k(w)(IAM) (electrostatic component of interaction with phospholipids). The results suggest that the electrostatic interactions encoded in log k(w)(IAM) values might act as trapping forces in a phospholipid barrier. Actually, we observed an inverse linear dependence of log BB on Delta log k(w)(IAM) values, but only for the compounds showing positive Delta log k(w)(IAM) values. We conclude that the driving force for BBB passage is the lipophilicity of the neutral forms, log P(N), and not the lipophilicity actually displayed at the experimental pH, log D(7.0). Indeed, the latter does not adequately take into account the role played by protonation in the analyte/membrane interactions because protonation, although hindering membrane passage, can either reduce or enhance partition in phospholipids, depending on analyte lipophilicity. PMID- 22306649 TI - Preparation and characterization of magnetizable aerosols. AB - Magnetizable aerosols can be used for inhalative magnetic drug targeting in order to enhance the drug concentration at a certain target site within the lung. The aim of the present study was to clarify how a typical ferrofluid can be atomized in a reproducible way. The influence of the atomization principle, the concentration of magnetic nanoparticles within the carrier liquid and the addition of commonly used pharmaceutical excipients on the aerosol droplet size were investigated. Iron oxide (magnetite) nanoparticles were synthesized by alkaline precipitation of mixtures of iron(II)- and iron(III)-chloride and coated with citric acid. The resulting ferrofluid was characterized by photon correlation spectroscopy and vibrating sample magnetometry. Two different nebulizers (Pari Boy and eFlow) with different atomization principles were used to generate ferrofluid aerosols. A range of substances that influence the surface tension, viscosity, density or vapor pressure of the ferrofluid were added to investigate their impact on the generated aerosol droplets. The particle size was determined by laser diffraction. A stable ferrofluid with a magnetic core diameter of 10.7 +/- 0.45 nm and a hydrodynamic diameter of 124 nm was nebulized by Pari Boy and eFlow. The aerosol droplet size of Pari Boy was approximately 2.5 MUm and remained unaffected by the addition of substances that changed the physical properties of the solvent. The droplet size of aerosols generated by eFlow was approximately 5 MUm. It was significantly reduced by the addition of Cremophor RH 40, glycerol, polyvinyl pyrrolidone and ethanol. PMID- 22306650 TI - Common variants at 11p13 are associated with susceptibility to tuberculosis. AB - After imputation of data from the 1000 Genomes Project into a genome-wide dataset of Ghanaian individuals with tuberculosis and controls, we identified a resistance locus on chromosome 11p13 downstream of the WT1 gene (encoding Wilms tumor 1). The strongest signal was obtained at the rs2057178 SNP (P = 2.63 * 10( 9)). Replication in Gambian, Indonesian and Russian tuberculosis case-control study cohorts increased the significance level for the association with this SNP to P = 2.57 * 10(-11). PMID- 22306651 TI - Differential confounding of rare and common variants in spatially structured populations. AB - Well-powered genome-wide association studies, now made possible through advances in technology and large-scale collaborative projects, promise to characterize the contribution of rare variants to complex traits and disease. However, while population structure is a known confounder of association studies, it remains unknown whether methods developed to control stratification are equally effective for rare variants. Here, we demonstrate that rare variants can show a stratification that is systematically different from, and typically stronger than, common variants, and this is not necessarily corrected by existing methods. We show that the same process leads to inflation for load-based tests and can obscure signals at truly associated variants. Furthermore, we show that populations can display spatial structure in rare variants, even when Wright's fixation index F(ST) is low, but that allele frequency-dependent metrics of allele sharing can reveal localized stratification. These results underscore the importance of collecting and integrating spatial information in the genetic analysis of complex traits. PMID- 22306652 TI - Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. AB - Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 * 10(-11); odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes. PMID- 22306653 TI - Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility. AB - Perlman syndrome is a congenital overgrowth syndrome inherited in an autosomal recessive manner that is associated with Wilms tumor susceptibility. We mapped a previously unknown susceptibility locus to 2q37.1 and identified germline mutations in DIS3L2, a homolog of the Schizosaccharomyces pombe dis3 gene, in individuals with Perlman syndrome. Yeast dis3 mutant strains have mitotic abnormalities. Yeast Dis3 and its human homologs, DIS3 and DIS3L1, have exoribonuclease activity and bind to the core RNA exosome complex. DIS3L2 has a different intracellular localization and lacks the PIN domain found in DIS3 and DIS3L1; nevertheless, we show that DIS3L2 has exonuclease activity. DIS3L2 inactivation was associated with mitotic abnormalities and altered expression of mitotic checkpoint proteins. DIS3L2 overexpression suppressed the growth of human cancer cell lines, and knockdown enhanced the growth of these cells. We also detected evidence of DIS3L2 mutations in sporadic Wilms tumor. These observations suggest that DIS3L2 has a critical role in RNA metabolism and is essential for the regulation of cell growth and division. PMID- 22306654 TI - Common variants near MBNL1 and NKX2-5 are associated with infantile hypertrophic pyloric stenosis. AB - Infantile hypertrophic pyloric stenosis (IHPS) is a severe condition characterized by hypertrophy of the pyloric sphincter muscle. We conducted a genome-wide association study (GWAS) on 1,001 surgery-confirmed cases and 2,401 controls from Denmark. The six most strongly associated loci were tested in a replication set of 796 cases and 876 controls. Three SNPs reached genome-wide significance. One of these SNPs, rs11712066 (odds ratio (OR) = 1.61; P = 1.5 * 10(-17)) at 3p25.1, is located 150 kb upstream of MBNL1, which encodes a factor that regulates splicing transitions occurring shortly after birth. The second SNP, rs573872 (OR = 1.41; P = 4.3 * 10(-12)), maps to an intergenic region at 3p25.2 approximately 1.3 Mb downstream of MBNL1. The third SNP, rs29784 (OR = 1.42; P = 1.5 * 10(-15)) at 5q35.2, is 64 kb downstream of NKX2-5, which is involved in development of cardiac muscle tissue and embryonic gut development. PMID- 22306656 TI - 5-Imino-1,2-4-thiadiazoles and quinazolines derivatives as glycogen synthase kinase 3beta (GSK-3beta) and phosphodiesterase 7 (PDE7) inhibitors: determination of blood-brain barrier penetration and binding to human serum albumin. AB - 5-Imino-1,2,4-thiadiazoles and quinazolines derivatives as glycogen synthase kinase 3beta (GSK-3beta) and phosphodiesterase 7 (PDE7) inhibitors were characterized for their ability to pass the blood-brain barrier (BBB) together with their human serum albumin (HSA) binding using high-performance liquid affinity chromatography (HPLAC) and circular dichroism (CD). To study the blood brain barrier penetration, a parallel artificial membrane permeability assay (PAMPA) using a porcine brain lipid was employed. For the HPLAC investigation, HSA was previously covalently immobilized to the silica matrix of the HPLC column. This HSA-based column was used to characterize the high affinity binding sites of 5-imino-1,2,4-thiadiazoles and quinazolines derivatives to HSA. Displacement experiments in the presence of increasing concentrations of competitors known to bind selectively to the main binding sites of HSA were carried out to determine their possible binding site. The same drug-protein system was studied by CD. The analysed compounds were able to pass BBB, they present good drug-like properties and they showed a high affinity to HSA. Competition experiments showed an anticooperative interaction at sites I and II, and an independent binding at bilirubin binding site on HSA. PMID- 22306655 TI - Voltage clamp methods for the study of membrane currents and SR Ca(2+) release in adult skeletal muscle fibres. AB - Skeletal muscle excitation-contraction (E-C)(1) coupling is a process composed of multiple sequential stages, by which an action potential triggers sarcoplasmic reticulum (SR)(2) Ca(2+) release and subsequent contractile activation. The various steps in the E-C coupling process in skeletal muscle can be studied using different techniques. The simultaneous recordings of sarcolemmal electrical signals and the accompanying elevation in myoplasmic Ca(2+), due to depolarization-initiated SR Ca(2+) release in skeletal muscle fibres, have been useful to obtain a better understanding of muscle function. In studying the origin and mechanism of voltage dependency of E-C coupling a variety of different techniques have been used to control the voltage in adult skeletal fibres. Pioneering work in muscles isolated from amphibians or crustaceans used microelectrodes or 'high resistance gap' techniques to manipulate the voltage in the muscle fibres. The development of the patch clamp technique and its variant, the whole-cell clamp configuration that facilitates the manipulation of the intracellular environment, allowed the use of the voltage clamp techniques in different cell types, including skeletal muscle fibres. The aim of this article is to present an historical perspective of the voltage clamp methods used to study skeletal muscle E-C coupling as well as to describe the current status of using the whole-cell patch clamp technique in studies in which the electrical and Ca(2+) signalling properties of mouse skeletal muscle membranes are being investigated. PMID- 22306657 TI - Cooperation, amplification, and feed-back in epithelial-mesenchymal transition. AB - The epithelial to mesenchymal transition (EMT) consists of a rapid change of cell phenotype, characterized by the loss of epithelial traits and the acquisition of a more motile phenotype reminiscent of a fibroblast. The study of this process has received considerable attention because of its potential role in the acquisition of several cancer traits, particularly in cell invasion. In this article we describe the current knowledge of the molecular mechanisms governing this transition. In particular we discuss how initiation of EMT is dependent on the mutually exclusive levels of the transmembrane cell to cell adhesion molecule E-cadherin and its transcriptional repressor Snail1 and how Snail1 and other E cadherin transcriptional repressors drive the EMT process. We focus on several new aspects of Snail1 regulation and propose a model for understanding the initiation and progression of this transition, based on the existence of feed back mechanisms that limit or amplify the response to extracellular cues. PMID- 22306658 TI - Snf1/AMPK regulates Gcn5 occupancy, H3 acetylation and chromatin remodelling at S. cerevisiae ADY2 promoter. AB - The ability of cells to respond to changes in their environment is mediated by transcription factors that remodel chromatin and reprogram expression of specific subsets of genes. In Saccharomyces cerevisiae, changes in carbon source lead to gene induction by Adr1 and Cat8 that are known to require the upstream function of the Snf1 protein kinase, the central regulator of carbon metabolism, to exert their activating effect. How Snf1 facilitates transcription activation by Adr1 and Cat8 is not known. Here we show that under derepressing conditions, deletion of SNF1 abolishes the increase of histone H3 acetylation at the promoter of the glucose-repressed ADY2 gene, and as a consequence profoundly affects the chromatin structural alterations accompanying transcriptional activation. Adr1 and Cat8 are not required to regulate the acetylation switch and show only a partial influence on chromatin remodelling at this promoter, though their double deletion completely abolishes mRNA accumulation. Finally, we show that under derepressing conditions the recruitment of the histone acetyltransferase Gcn5 is abolished by SNF1 deletion, possibly explaining the lack of increased histone H3 acetylation and nucleosome remodelling. The results highlight a mechanism by which signalling to chromatin provides an essential permissive signal that is required for activation by glucose-responsive transcription factors. PMID- 22306659 TI - mRNA export and sumoylation-Lessons from plants. AB - SUMO is a small ubiquitin-related protein modifier that is involved in a number of biological processes, including transcription, DNA repair, genome stability, and chromatin organization. Its potential role in mRNA biogenesis is less well investigated. The biogenesis of mRNA is closely coupled to transcription as well as mRNA nuclear export and several of the involved proteins have dual roles and appear in several complexes. Recently, SUMO-proteome analyses have discovered a number of these proteins as putative targets of SUMO regulation. In the model plant Arabidopsis thaliana, several mutants as well as environmental conditions have been identified that show a close correlation between over- and under sumoylation of nuclear proteins and mRNA export retention. Three new plant SUMO proteome studies add to the list of potentially sumoylated RNA-related proteins. Here, the emerging connection between SUMO and mRNA export is compared across kingdoms and its potential mechanistic role is discussed. This article is part of a Special Issue entitled: Nuclear Transport and RNA Processing. PMID- 22306660 TI - Hitchhiking on host chromatin: how papillomaviruses persist. AB - Persistent viruses need mechanisms to protect their genomes from cellular defenses and to ensure that they are efficiently propagated to daughter host cells. One mechanism by which papillomaviruses achieve this is through the association of viral genomes with host chromatin, mediated by the viral E2 tethering protein. Association of viral DNA with regions of active host chromatin ensures that the virus remains transcriptionally active and is not relegated to repressed heterochromatin. In addition, viral genomes are tethered to specific regions of host mitotic chromosomes to efficiently partition their DNA to daughter cells. Vegetative viral DNA replication also initiates at specific regions of host chromatin, where the viral E1 and E2 proteins initiate a DNA damage response that recruits cellular DNA damage and repair proteins to viral replication foci for efficient viral DNA synthesis. Thus, these small viruses have capitalized on interactions with chromatin to efficiently target their genomes to beneficial regions of the host nucleus. This article is part of a Special Issue entitled: Chromatin in time and space. PMID- 22306661 TI - Insights into the mechanism of activation of the phosphorylation-independent response regulator NblR. Role of residues Cys69 and Cys96. AB - Cyanobacteria respond to environmental stress conditions by adjusting their photosynthesis machinery. In Synechococcus sp. PCC 7942, phycobilisome degradation and other acclimation responses after nutrient or high light stress require activation by the phosphorylation-independent response regulator NblR. Structural modelling of its receiver domain suggested a role for Cys69 and Cys96 on activation of NblR. Here, we investigate this hypothesis by engineering Cys to Ala substitutions. In vivo and in vitro analyses indicated that mutations Cys69Ala and/or Cys96Ala have a minor impact on NblR function, structure, size, or oligomerization state of the protein, and that Cys69 and Cys96 do not seem to form disulphide bridges. Our results argue against the predicted involvement of Cys69 and Cys96 on NblR activation by redox sensing. PMID- 22306662 TI - Perfect and imperfect nucleosome positioning in yeast. AB - Numerous studies of nucleosome positioning have shown that nucleosomes almost invariably adopt one of several alternative overlapping positions on a short DNA fragment in vitro. We define such a set of overlapping positions as a "position cluster", and the 5S RNA gene positioning sequence is presented as an example. The notable exception is the synthetic 601-sequence, which can position a nucleosome perfectly in vitro, though not in vivo. Many years ago, we demonstrated that nucleosome position clusters are present on the CUP1 and HIS3 genes in native yeast chromatin. Recently, using genome-wide paired-end sequencing of nucleosomes, we have shown that position clusters are the general rule in yeast chromatin, not the exception. We argue that, within a cell population, one of several alternative nucleosomal arrays is formed on each gene. We show how position clusters and alternative arrays can give rise to typical nucleosome occupancy profiles, and that position clusters are disrupted by transcriptional activation. The centromeric nucleosome is a rare example of perfect positioning in vivo. It is, however, a special case, since it contains the centromeric histone H3 variant instead of normal H3. Perfect positioning might be due to centromeric sequence-specific DNA binding proteins. Finally, we point out that the existence of position clusters implies that the putative nucleosome code is degenerate. We suggest that degeneracy might be a crucial point in the debate concerning the code. This article is part of a Special Issue entitled: Chromatin in time and space. PMID- 22306663 TI - Chromosome dynamics in multichromosome bacteria. AB - On the basis of limited information, bacteria were once assumed to have no more than one chromosome. In the era of genomics, it has become clear that some, like eukaryotes, have more than one chromosome. Multichromosome bacteria provide opportunities to investigate how split genomes emerged, whether the individual chromosomes communicate to coordinate their replication and segregation, and what selective advantages split genomes might provide. Our current knowledge of these topics comes mostly from studies in Vibrio cholerae, which has two chromosomes, chr1 and chr2. Chr1 carries out most of the house-keeping functions and is considered the main chromosome, whereas chr2 appears to have originated from a plasmid and has acquired genes of mostly unknown origin and function. Nevertheless, unlike plasmids, chr2 replicates once and only once per cell cycle, like a bona fide chromosome. The two chromosomes replicate and segregate using separate programs, unlike eukaryotic chromosomes. They terminate replication synchronously, suggesting that there might be communication between them. Replication of the chromosomes is affected by segregation genes but in a chromosome specific fashion, a new development in the field of DNA replication control. The split genome allows genome duplication to complete in less time and with fewer replication forks, which could be beneficial for genome maintenance during rapid growth, which is the norm for V. cholerae in broth cultures and in the human host. In the latter, the expression of chr2 genes increases preferentially. Studies of chromosome maintenance in multichromosomal bacteria, although in their infancy, are already broadening our view of chromosome biology. This article is part of a Special Issue entitled: Chromatin in time and space. PMID- 22306664 TI - The transcription cycle in eukaryotes: from productive initiation to RNA polymerase II recycling. AB - The cycle of eukaryotic transcription, from initiation to elongation and termination is regulated at multiple steps. Coordinated action of regulatory factors keeps in check the transcriptional competence of RNA polymerase II (RNAPII) at different stages. Productive transcription requires the escape of the paused RNAPII from the promoter and transition to rapid elongation of the transcript. Numerous studies have identified diverse mechanisms of initiating transcription by overriding inhibitory signals at the gene promoter. The general theme that has emerged is that the balance between positive and negative regulatory factors determines the overall rate of transcription. Recently transcription termination has emerged as an important area of transcriptional regulation that is coupled with the efficient recycling of RNAPII. The factors associated with transcription termination can also mediate gene looping and thereby determine the efficiency of re-initiation. This review highlights these regulatory steps, the key modulators involved in transcription dynamics, and the emerging tools to analyze them. PMID- 22306665 TI - Evaluation of quantitative debriefing after pediatric cardiac arrest. AB - AIM: Our primary objective was to describe and determine the feasibility of implementing a care environment targeted pediatric post-cardiac arrest debriefing program. A secondary objective was to evaluate the usefulness of debriefing content items. We hypothesized that a care environment targeted post-cardiac arrest debriefing program would be feasible, well-received, and result in improved self-reported knowledge, confidence and performance of pediatric providers. METHODS: Physician-led multidisciplinary pediatric post-cardiac arrest debriefings were conducted using data from CPR recording defibrillators/central monitors followed by a semi-quantitative survey. Eight debriefing content elements divided, a priori, into physical skill (PS) related and cognitive skill (CS) related categories were evaluated on a 5-point Likert scale to determine those most useful (5-point Likert scale: 1=very useful/5=not useful). Summary scores evaluated the impact on providers' knowledge, confidence, and performance. RESULTS: Between June 2010 and May 2011, 6 debriefings were completed. Thirty four of 50 (68%) front line care providers attended the debriefings and completed surveys. All eight content elements were rated between useful to very useful (Median 1; IQR 1-2). PS items scored higher than CS items to improve knowledge (Median: 2 (IQR 1-3) vs. 1 (IQR 0-2); p<0.02) and performance (Median: 2 (IQR 1 3) vs. 1 (IQR 0-1); p<0.01). CONCLUSIONS: A novel care environment targeted pediatric post-cardiac arrest pediatric debriefing program is feasible and useful for providers regardless of their participation in the resuscitation. Physical skill related elements were rated more useful than cognitive skill related elements for knowledge and performance. PMID- 22306666 TI - Out of hospital "smart" resuscitation. PMID- 22306667 TI - ECGs: colour-coding for initial training. PMID- 22306668 TI - Maternal oxytocin response during mother-infant interaction: associations with adult temperament. AB - Oxytocin is a neuropeptide associated with social affiliation and maternal caregiving. However, its effects appear to be moderated by various contextual factors and stable individual characteristics. The purpose of this study was to investigate the relationship of self-reported state and trait measures (such as temperament, mood and affect) with peripheral oxytocin response in mothers. Fifty five first-time mothers participated in a semi-structured procedure, during which time repeated peripheral oxytocin levels were measured before, during and after an episode of mother-infant interaction. The maternal oxytocin response was then calculated, based on the difference in oxytocin concentration between initial baseline and interaction phase. Mothers also completed state measures of positive and negative affect and depression, and trait measures of temperament, personality disturbance and depression across time. Regression analyses determined which factors were independently associated with maternal oxytocin response. The trait measure of adult temperament emerged as a significant predictor of oxytocin response. Two out of four Adult Temperament Questionnaire factor scales were independently associated with oxytocin response: Effortful Control was negatively associated, whereas Orienting Sensitivity was positively associated. No state measure significantly predicted oxytocin response. The results indicate that mothers who show an increased oxytocin response when interacting with their infants are more sensitive of moods, emotions and physical sensations; and less compulsive, schedule driven and task oriented. These findings link differences in individual temperament in new mothers with the peripheral oxytocin response, which may have implications in the pharmacologic treatment of disorders such as maternal neglect, post-partum depression and maternal addiction. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior. PMID- 22306669 TI - Analytical performance of a real-time PCR-based assay for V600 mutations in the BRAF gene, used as the companion diagnostic test for the novel BRAF inhibitor vemurafenib in metastatic melanoma. AB - Melanomas frequently harbor BRAFV600 mutations. Vemurafenib (RG7204/PLX4032), a small-molecule inhibitor of mutant BRAF, has shown striking clinical efficacy in BRAFV600 mutant melanoma, creating the need for a well-validated companion diagnostic to select patients for treatment. We describe analytic performance characteristics of the cobas 4800 BRAF V600 Mutation Test, the test used to select patients for the pivotal vemurafenib trials. This real-time polymerase chain reaction assay was designed to detect the V600E (1799T>A) mutation DNA from formalin-fixed paraffin-embedded tissue samples. Sensitivity was assessed using blends of cell lines or tumor DNA, and tumor specimens with low levels of mutant alleles, as determined by 454 sequencing (a quantitative next-generation pyrosequencing method). A >96% hit rate was obtained across all specimen types with 5% mutant alleles at a DNA input of 125 ng, an amount readily obtained from one 5-MUm section. The cobas test showed a higher sensitivity and specificity than direct bidirectional sequencing in a panel of 219 melanoma specimens. Cross reactivity with V600K and V600D was observed. Repeated testing of 5 specimens by 2 operators, using different instruments and reagent lots, yielded correct calls in 158/160 tests (98.8%). A set of 26 highly pigmented samples were identified that gave invalid test results. A simple 1:2 dilution resulted in a valid test result of 76% in such cases. The cobas test is a reproducible assay that detects some non-V600E mutations and is more accurate than direct sequencing in detecting BRAFV600E. PMID- 22306670 TI - Comparison of a PNA clamp PCR and an ARMS/Scorpion PCR assay for the detection of K-ras mutations. AB - Point mutations in the K-ras gene have been shown to confer resistance against epidermal growth factor receptor-directed therapy of metastatic colorectal cancer. Accordingly, K-ras mutation testing has become mandatory in hospitals offering such treatment. We compared the performance and reagent costs of 2 sensitive methods for detection of K-ras mutations: a peptide nucleic acid (PNA) clamp polymerase chain reaction (PCR) assay and a commercially available amplification refractory mutation system/Scorpion (ARMS/S) PCR assay. Both methods were applied in parallel to 101 formalin-fixed, paraffin-embedded tumor and metastasis samples from patients with colon cancer. The PNA clamp PCR assay detected K-ras mutations in 35% (35 of 101) of the samples, whereas the ARMS/S PCR assay detected mutations in 27% (27 of 101) of them. There was 92% (93 of 101) concordance between the 2 methods and the kappa coefficient for the comparison was 0.82. The 8 discordant cases were exclusively positive by PNA clamp PCR. Finally, the reagent costs of the PNA clamp PCR assay were estimated to be at least 20 times lower than the ARMS/S assay. We concluded that the high performance and low costs associated with the PNA clamp PCR assay encourage its use in the administration of personalized epidermal growth factor receptor directed therapy. PMID- 22306671 TI - KRAS mutation testing in colorectal cancer: comparison of the results obtained using 3 different methods for the analysis of codons G12 and G13. AB - Targeting the epidermal growth factor receptor (EGFR) is a new therapeutic option for patients with metastatic colorectal or lung carcinoma. However, the therapy efficiency highly depends on the KRAS mutation status in the given tumour. Therefore a reliable and secure KRAS mutation testing is crucial. Here we investigated 100 colorectal carcinoma samples with known KRAS mutation status (62 mutated cases and 38 wild type cases) in a comparative manner with three different KRAS mutation testing techniques (Pyrosequencing, Dideoxysequencing and INFINITI) in order to test their reliability and sensitivity. For the large majority of samples (96/100, 96%), the KRAS mutation status obtained by all three methods was the same. Only two cases with clear discrepancies were observed. One case was reported as wild type by the INFINITI method while the two other methods detected a G13C mutation. In the second case the mutation could be detected by the Pyrosequencing and INFINITI method (15% and 15%), while no signal for mutation could be observed with the Dideoxysequencing method. Additional two unclear results were due to a detection of a G12V with the INFINITI method, which was below cut-off when repeated and which was not detectable by the other two methods and very weak signals in a G12V mutated case with the Dideoxy- and Pyroseqencing method compared to the INFINITI method, respectively. In summary all three methods are reliable and robust methods in detecting KRAS mutations. INFINITI, however seems to be slightly more sensitive compared to Dideoxy- and Pyrosequencing. PMID- 22306672 TI - Methylation variable position profiles of hMLH1 promoter CpG islands in human sporadic colorectal carcinoma. AB - Aberrant hypermethylation of CpG islands (CGIs) in hMLH1 promoter regions has been well known to play an important role in the tumorigenesis of human sporadic colorectal carcinoma (SCRC). In this study, bisulfite sequencing was performed to analyze the methylation variable positions (MVPs) profiles of hMLH1 promoter CGIs in 30 clinical SCRC patients, and further analysis was carried out to evaluate the associations between the CGI methylation and the clinicopathological features in SCRC. Among the 2 CGIs in the hMLH1 promoter, that is, CGI-I and CGI-II, 20% (6/30) and 13% (4/30) of the patients had methylated CGI-I and CGI-II, respectively. Suppressed expression of hMLH1was significantly correlated with methylation of CGI-I but not CGI-II. Further analysis of the MVP profiles of CGI I showed that most of the MVPs were hypermethylated and others were poorly methylated or unmethylated. The profiles could be classified into at least 4 groups based on the methylation status of 3 MVPs at positions 21 to 23 in CGI-I. All 6 patients with methylated CGI-I belonged to group I. This result suggests that the above 3 MVPs in CGI-I should be a targeted region to further analyze the epigenetic features of hMLH1 in human SCRC. Our results further suggest that MVP profiling is useful for identifying the aberrantly methylated CGIs associated with suppressed gene expression. PMID- 22306673 TI - Rapid quantitative detection of the T315I mutation in patients with chronic myelogenous leukemia. AB - Acquired resistance to tyrosine kinase inhibitors (TKIs) in the treatment of chronic myelogenous leukemia (CML) is frequently caused by point mutations in the ABL kinase domain of the BCR-ABL fusion gene. The T315I mutation is the most common mutation found in the kinase domain and leads to complete resistance to existing TKIs. Sensitive and specific approaches for detecting this mutation in patient specimens can provide valuable information to guide treatment decisions and monitor their effectiveness. Here, we describe an allele-specific real-time polymerase chain reaction method to distinguish and quantify wild type or T315I mutant ABL transcripts. This approach has high specificity in identifying mutant transcripts and shows minimal interference from wild-type transcripts. As few as 5 copies of the T315I mutant transcript or 0.025% (2.5*10(-4)) T315I mutant transcripts could be detected by this method. This approach requires no additional specialized reagents other than those used in standard real-time polymerase chain reaction and therefore may be easily incorporated as an effective strategy for the early detection and monitoring of TKI resistance in patients with CML. PMID- 22306674 TI - Diagnostic utility of a multiplex RT-PCR assay in detecting fusion transcripts from recurrent genetic abnormalities of acute leukemia by WHO 2008 classification. AB - Fusion transcripts (FT) from chromosomal rearrangements are key culprits in acute leukemia, with genotype-phenotype correlations including prognostic implications. Here, we report our experience of a commercially available platform utilizing multiplex reverse-transcriptase polymerase chain reaction (RT-PCR), HemaVision, in 309 consecutive patients with acute leukemia. A total of 108 patients (35%) were diagnosed as having acute leukemia with recurrent genetic abnormalities by the World Health Organization 2008 classification. The multiplex RT-PCR platform, detected 12 different FT in 92 (85.2%; 92/108), with a 99% concordance rate with conventional cytogenetics/fluorescence in situ hybridization. Additional information obtained from the multiplex RT-PCR assay included transcript heterogeneity and novel splice variants of FT. In addition, the RT-PCR assay targeting specific FT could be used for monitoring minimal residual disease. HemaVision is a robust diagnostic platform in detecting FT in routine clinical laboratories both at initial diagnosis and for disease monitoring. PMID- 22306675 TI - Comparison of 2 different PCR-based technologies for the detection of human papilloma virus from paraffin-embedded tissue: genomica clinical arrays versus SPF(10)-LiPA(25). AB - The great interest in molecular epidemiology of human papilloma virus (HPV) in cervical cancer led us to perform a thorough evaluation of 2 polymerase chain reaction (PCR)-based methods for the detection of HPV in archival formalin-fixed paraffin-embedded (FFPE) samples. Thus, the aim of this study was to compare HPV detection in FFPE samples that have histopathologic diagnosis of invasive cervical cancer using SPF10 broad-spectrum primers PCR followed by DNA enzyme immunoassay and LiPA25 (version 1: Labo Biomedical products, Rijswijk, The Netherlands version 1) and the Papillomavirus Clinical Arrays technique (Genomica, Tres Cantos, Madrid, Spain). In this study, 235 biopsies with histopathologic diagnosis of invasive cervical cancer were analyzed for the detection and genotyping of HPV by LiPA25 SPF10-PCR System (version 1) and Papillomavirus Clinical Arrays technique. The detection of HPV DNA with Genomica technique was 75.1%, and 91.9% with LiPA25 SPF10-PCR. The Genomica technique detected a higher percentage of multiple infections (35%) than LiPA25 (8.9%), with a very low agreement for the detection of multiple infections between them (P>0.05). Our study highlights an important difference between 2 PCR-based methods for detection and genotyping of HPV. LiPA25 SPF10-PCR technology may be more adequate than Genomica for the detection of HPV DNA when using FFPE tissue. PMID- 22306676 TI - Analysis of cDNA molecules is not suitable for the molecular diagnosis of Mucopolysaccharidosis type I. AB - Nonsense-mediated decay (NMD) is a mechanism of the recognition and degradation of messenger RNA containing a premature stop codon. Nonsense mutations are the main mutations that lead to Mucopolysaccharidosis type I. To determine the effect of NMD on correct genotyping based on cDNA sequencing, we standardized the sequencing from alpha-L-iduronidase gene cDNA molecules and validated this process for a group of patients whose mutations had been previously identified by DNA analysis. Although the whole gene could be amplified in 5 polymerase chain reactions, cDNA proved unsuitable for molecular analysis as patients bearing splice site and nonsense mutations were not genotyped. PMID- 22306677 TI - Personalized medicine switching from insulin to sulfonylurea in permanent neonatal diabetes mellitus dictated by a novel activating ABCC8 mutation. AB - BACKGROUND: Neonatal diabetes mellitus (NDM) is a rare but important condition affecting approximately 1 in 100,000 newborns. Permanent form requires life-long treatment with difficulties in long-term compliance and metabolic complications. Exact genetic diagnosis can enable improved outcome and patient satisfaction by switching insulin injection to oral sulfonylureas. Successful cases have been reported with most experience on the KCNJ11-mutated permanent form. Here we report a successful experience in an ABCC8-mutated infant with permanent NDM. PATIENT AND METHODS: A 4-month-old Chinese girl was incidentally found to have hyperglycemia with baseline C-peptide of 0.05 nmol/L requiring insulin injection of 0.2 IU/kg/d. Genetic analysis of KCNJ11 and ABCC8 was performed by polymerase chain reaction and direct DNA sequencing at the age of 3 years. Sulfonylurea transition was conducted after the ABCC8 mutation detection. RESULTS: A novel homozygous ABCC8 NM_000352.3: c.3068 A>G; NP_000343.2: p.H1023R mutation was detected. C-peptide level increased to 0.14 nmol/L and HbA1c was normalized to 5.8% from 8.0% after 8 months of oral glibenclamide treatment with a maintenance dosage of 0.65 mg/kg/d. CONCLUSIONS: In this patient with ABCC8-mutated permanent NDM, oral sulfonylurea is also effective in achieving satisfactory diabetic control. Our study adds information to the personalized medicine practice of ABCC8-mutated permanent NDM. PMID- 22306678 TI - The influence of unattended features on object processing depends on task demand. AB - Objects consist of features such as shape, motion and color, all of which can be selectively used for different object processing tasks. The present study investigated whether task demands influenced how well participants attended to features of novel colored dynamic objects that were task-relevant while ignoring those that were task-irrelevant. To address this, we used tasks which had different perceptual, learning and memory demands. The unattended features were systematically changed to measure their effects on how well participants could process the attended feature. In Experiment 1, participants discriminated simultaneously presented objects on the basis their shape or motion. We found that changes to unattended motion and color did not affect participants' sensitivity to discriminate the attended feature but changes to unattended shape did. We also found that changes to unattended motion impaired how quickly observers responded. In Experiment 2, participants identified learned objects at the individual level on the basis of their shape or motion. We found that changes to any unattended features affected accuracy and reaction times. Overall, these results point to an important role of task demands in object processing: Task demands can influence whether task-irrelevant features affect object-processing performance. PMID- 22306679 TI - Word processing speed in peripheral vision measured with a saccadic choice task. AB - A saccadic choice task (Kirchner & Thorpe, 2006) was used to measure word processing speed in peripheral vision. To do so, word targets were accompanied by distractor stimuli, which were random strings of consonants presented in the contralateral visual field. Participants were also tested with the animal stimuli of Kirchner and Thorpe's original study. The results obtained with the animal stimuli provide a straightforward replication of prior findings, with the estimated fastest saccade latencies to animal targets being 140 ms. With the word targets, the fastest reliable saccades occurred with latencies of around 200 ms. The results obtained with word targets provide a timing estimate for word processing in peripheral vision that is incompatible with sequential-attention shift (SAS) accounts of eye movement control in reading. PMID- 22306680 TI - Luminance and chromatic contributions to a hyperacuity task: isolation by contrast polarity and target separation. AB - Vernier thresholds are known to be elevated when a target pair has opposite contrast polarity. Polarity reversal is used to assess the role of luminance and chromatic pathways in hyperacuity performance. Psychophysical hyperacuity thresholds were measured for pairs of gratings of various combinations of luminance (Lum) and chromatic (Chr) contrast polarities, at different ratios of luminance to chromatic contrast. With two red-green gratings of matched luminance and chromatic polarity (+Lum+Chr), there was an elevation of threshold at isoluminance. When both luminance and chromatic polarity were mismatched (-Lum Chr), thresholds were substantially elevated under all conditions. With the same luminance contrast polarity and opposite chromatic polarity (+Lum-Chr) thresholds were only elevated close to isoluminance; in the reverse condition (-Lum+Chr), thresholds were elevated as in the -Lum-Chr condition except close to equiluminance. Similar data were obtained for gratings isolating the short wavelength cone mechanism. Further psychophysical measurements assessed the role of target separation with matched or mismatched contrast polarity; similar results were found for luminance and chromatic gratings. Comparison physiological data were collected from parafoveal ganglion cells of the macaque retina. Positional precision of ganglion cell signals was assessed under conditions related to the psychophysical measurements. On the basis of these combined observations, it is argued that both magnocellular, parvocellular, and koniocellular pathways have access to cortical positional mechanisms associated with vernier acuity. PMID- 22306681 TI - A fluid biopsy as investigating technology for the fluid phase of solid tumors. PMID- 22306682 TI - Encapsulated papillary thyroid carcinoma: is it a distinctive clinical entity with low-grade malignancy? AB - BACKGROUND: Encapsulated papillary thyroid carcinoma (EPTC) is commonly retained as a tumor with indolent clinical courses. Herein we focused on the search for factors predicting biological behavior and influencing prognosis of EPTC in comparison with the non-encapsulated counterpart of papillary thyroid carcinoma (NEPTC). METHODS: From January 1998 to May 2009, 348 patients underwent thyroidectomy in our surgical department because of papillary thyroid carcinoma (PTC). A cross-sectional study of 52 patients with EPTC and 296 patients with NEPTC was carried out: demographic data, tumor characteristics, diagnostic results, patient management, post-operative and follow-up results were evaluated. RESULTS: EPTC patients were significantly younger than patients with NEPTC (44.5 vs 48.8 yr, p<0.04). Mean tumor size was significantly greater for EPTC than for NEPTC (2.36 vs 1.41 cm, p<0.001). Tumor multifocality, thyroid capsular invasion, and lymph node involvement at diagnosis were significantly associated with NEPTC (p=0.0001, p<0.0001, and p=0.027, respectively). Multivariate analyses showed that NEPTC classical variant were at risk for both thyroid capsular invasion and nodal involvement (odds ratio 6.870 and 9.514, respectively) while EPTC were not. Nodal metastasis at diagnosis was the only factor influencing recurrence. CONCLUSIONS: The majority of EPTC had risk-free clinical courses as a result of their low risk of locoregional spread. However, definitive recommendations need a longer follow-up and a comparison with a lesser treated group of patients belonging to the same category of risk at diagnosis. PMID- 22306688 TI - Development and implementation of a web-enabled 3D consultation tool for breast augmentation surgery based on 3D-image reconstruction of 2D pictures. AB - BACKGROUND: Producing a rich, personalized Web-based consultation tool for plastic surgeons and patients is challenging. OBJECTIVE: (1) To develop a computer tool that allows individual reconstruction and simulation of 3 dimensional (3D) soft tissue from ordinary digital photos of breasts, (2) to implement a Web-based, worldwide-accessible preoperative surgical planning platform for plastic surgeons, and (3) to validate this tool through a quality control analysis by comparing 3D laser scans of the patients with the 3D reconstructions with this tool from original 2-dimensional (2D) pictures of the same patients. METHODS: The proposed system uses well-established 2D digital photos for reconstruction into a 3D torso, which is then available to the user for interactive planning. The simulation is performed on dedicated servers, accessible via Internet. It allows the surgeon, together with the patient, to previsualize the impact of the proposed breast augmentation directly during the consultation before a surgery is decided upon. We retrospectively conduced a quality control assessment of available anonymized pre- and postoperative 2D digital photographs of patients undergoing breast augmentation procedures. The method presented above was used to reconstruct 3D pictures from 2D digital pictures. We used a laser scanner capable of generating a highly accurate surface model of the patient's anatomy to acquire ground truth data. The quality of the computed 3D reconstructions was compared with the ground truth data used to perform both qualitative and quantitative evaluations. RESULTS: We evaluated the system on 11 clinical cases for surface reconstructions and 4 clinical cases of postoperative simulations, using laser surface scan technologies showing a mean reconstruction error between 2 and 4 mm and a maximum outlier error of 16 mm. Qualitative and quantitative analyses from plastic surgeons demonstrate the potential of these new emerging technologies. CONCLUSIONS: We tested our tool for 3D, Web-based, patient-specific consultation in the clinical scenario of breast augmentation. This example shows that the current state of development allows for creation of responsive and effective Web-based, 3D medical tools, even with highly complex and time-consuming computation, by off-loading them to a dedicated high-performance data center. The efficient combination of advanced technologies, based on analysis and understanding of human anatomy and physiology, will allow the development of further Web-based reconstruction and predictive interfaces at different scales of the human body. The consultation tool presented herein exemplifies the potential of combining advancements in the core areas of computer science and biomedical engineering with the evolving areas of Web technologies. We are confident that future developments based on a multidisciplinary approach will further pave the way toward personalized Web-enabled medicine. PMID- 22306689 TI - Percent-predicted 6-minute walk distance in duchenne muscular dystrophy to account for maturational influences. AB - We recently described a modified version of the 6-minute walk test (6MWT) for Duchenne muscular dystrophy (DMD) based partly on the American Thoracic Society (ATS) guidelines. This measure has shown reliability, validity and utility as a primary outcome measure in DMD clinical trials. Because loss of muscle function in DMD occurs against the background of normal childhood growth and development, younger children with DMD can show increase in distance walked during 6MWT over ~1 year despite progressive muscular impairment. In this study, we compare 6 minute walk distance (6MWD) data from DMD boys (n=17) and typically developing control subjects (n=22) to existing normative data from age- and sex-matched children and adolescents. An age- and height-based equation fitted to normative data by Geiger and colleagues was used to convert 6MWD to a percent-predicted (% predicted) value in boys with DMD. Analysis of %-predicted 6MWD data represents a method to account for normal growth and development, and shows that gains in function at early ages represents stable rather than improving abilities in boys with DMD. Boys with DMD from 4-7 years of age maintain a stable 6MWD approximately 80% of that of typically developing peers, with the deficit progressing at a variable rate thereafter. PMID- 22306690 TI - Elevated and sustained expression of the transcription factors Egr1 and Egr2 controls NKT lineage differentiation in response to TCR signaling. AB - Interactions driven by the T cell antigen receptor (TCR) determine the lineage fate of CD4(+)CD8(+) thymocytes, but the molecular mechanisms that induce the lineage-determining transcription factors are unknown. Here we found that TCR induced transcription factors Egr2 and Egr1 had higher and more-prolonged expression in precursors of the natural killer T (NKT) than in cells of conventional lineages. Chromatin immunoprecipitation followed by deep sequencing showed that Egr2 directly bound and activated the promoter of Zbtb16, which encodes the NKT lineage-specific transcription factor PLZF. Egr2 also bound the promoter of Il2rb, which encodes the interleukin 2 (IL-2) receptor beta-chain, and controlled the responsiveness to IL-15, which signals the terminal differentiation of the NKT lineage. Thus, we propose that persistent higher expression of Egr2 specifies the early and late stages of NKT lineage differentiation, providing a discriminating mechanism that enables TCR signaling to 'instruct' a thymic lineage. PMID- 22306691 TI - The composition and signaling of the IL-35 receptor are unconventional. AB - Interleukin 35 (IL-35) belongs to the IL-12 family of heterodimeric cytokines but has a distinct functional profile. IL-35 suppresses T cell proliferation and converts naive T cells into IL-35-producing induced regulatory T cells (iTr35 cells). Here we found that IL-35 signaled through a unique heterodimer of receptor chains IL-12Rbeta2 and gp130 or homodimers of each chain. Conventional T cells were sensitive to IL-35-mediated suppression in the absence of one receptor chain but not both receptor chains, whereas signaling through both chains was required for IL-35 expression and conversion into iTr35 cells. Signaling through the IL-35 receptor required the transcription factors STAT1 and STAT4, which formed a unique heterodimer that bound to distinct sites in the promoters of the genes encoding the IL-12 subunits p35 and Ebi3. This unconventional mode of signaling, distinct from that of other members of the IL-12 family, may broaden the spectrum and specificity of IL-35-mediated suppression. PMID- 22306692 TI - A CD74-dependent MHC class I endolysosomal cross-presentation pathway. AB - Immune responses are initiated and primed by dendritic cells (DCs) that cross present exogenous antigen. The chaperone CD74 (invariant chain) is thought to promote DC priming exclusively in the context of major histocompatibility complex (MHC) class II. However, we demonstrate here a CD74-dependent MHC class I cross presentation pathway in DCs that had a major role in the generation of MHC class I-restricted, cytolytic T lymphocyte (CTL) responses to viral protein- and cell associated antigens. CD74 associated with MHC class I in the endoplasmic reticulum of DCs and mediated the trafficking of MHC class I to endolysosomal compartments for loading with exogenous peptides. We conclude that CD74 has a previously undiscovered physiological function in endolysosomal DC cross presentation for priming MHC class I-mediated CTL responses. PMID- 22306693 TI - Virulence of Vibrio harveyi responsible for the "Bright-red" Syndrome in the Pacific white shrimp Litopenaeus vannamei. AB - Vibrio harveyi (Vh) CAIM 1792 strain was isolated from Litopenaeus vannamei affected with "Bright-red" Syndrome (BRS). The strain grew in 1-10% NaCl, at 15 35 degrees C and was resistant to ampicillin (10 MUg), carbenicillin (100 MUg) and oxytetracycline (30 MUg). The lowest MIC was for enrofloxacine (0.5 MUgml( 1)). The in vivo and in vitro toxicity of bacterial cells and the extracellular products (ECPs) of Vh CAIM 1792 grown at 1.0%, 2.0% and 4.0% NaCl were evaluated. Adherence ability, enzymatic activities and siderophore production of bacterial cell was tested. The ECPs exhibited several enzymatic activities, such as gelatinase, amylase, lipase, phospholipase and caseinase. These ECPs displayed a strong cytotoxic effect on HELA cell line at 6 and 24 h. Challenges using 10(3) CFU g(-1) caused opacity at the site of injection and over 80% shrimp mortality before 24 h p.i. (post-injection). Mortality caused by the ECPs was higher than mortalities with bacteria, especially in the first hours p.i. Bacteria were re isolated from hemolymph samples of moribund shrimp and identified as Vh CAIM 1792 by rep-PCR. Histological analysis of shrimp L. vannamei injected with Vh CAIM 1792 revealed generalized necrosis involving skeletal muscle (MU) at the injection site, the lymphoid organ (LO), heart and connective tissues. Melanization within the MU at the site of injection was also observed as well as hemocytic nodules within the hearth and MU at 168 h p.i. LO was the target organ of BRS. Necrosis of the MU at the injection site was the main difference in comparison to other shrimp vibriosis. PMID- 22306694 TI - Risk assessment of premature drug release during wet granulation of ordered mesoporous silica loaded with poorly soluble compounds itraconazole, fenofibrate, naproxen, and ibuprofen. AB - In this study, the potential of wet granulation of ordered mesoporous silica (OMS) material was evaluated to assess the risk of premature drug release during processing and to improve the bulk powder flow properties and compactibility for the development of an immediate release oral dosage form. The poorly water soluble model compounds, itraconazole, fenofibrate, naproxen, and ibuprofen were loaded into the model OMS, COK-12, and granulated using a polyvinylpyrrolidone (PVP) binder solution. Preliminary assessments were made with itraconazole loaded COK-12 to study the effects of the initial drug load, binder concentration, binder addition rate, and granulation temperature on premature drug release. Comparison to pure COK-12 revealed particle size enlargement and enhanced powder flow based on Carr Index and Hausner Ratio results. Following compression to 120 MPa, the compactibility of the granulated material also improved when compared to the untreated COK-12. In vitro release of itraconazole from the compressed granulated material was assessed with and without the disintegrant, croscarmellose sodium. Incorporation of 2.4 wt. croscarmellose sodium prior to compression successfully recovered the slight release loss following compression. To assess premature drug release, developments made with itraconazole loaded COK 12 were applied to loaded fenofibrate, naproxen, and ibuprofen. Results from modulated differential scanning calorimetry (MDSC) indicated that the risk of premature drug release during wet granulation was primarily compound dependent. These findings highlight challenges in preparation for a successful manufacturing process of OMS based formulations. PMID- 22306695 TI - Genetic variation in TRPS1 may regulate hip geometry as well as bone mineral density. AB - Trps1 has been proposed as a candidate gene for a mouse bone mineral density (BMD) QTL on Chromosome (Chr) 15, but it remained unclear if this gene was associated with BMD in humans. We used newly available data and advanced bioinformatics techniques to confirm that Trps1 is the most likely candidate gene for the mouse QTL. In short, by combining the raw genetic mapping data from two F2 generation crosses of inbred strains of mice, we narrowed the 95% confidence interval of this QTL down to the Chr 15 region spanning from 6 to 24cM. This region contains 131 annotated genes. Using block haplotyping, all other genes except Trps1 were eliminated as candidates for this QTL. We then examined associations of 208 SNPs within 10kb of TRPS1 with BMD and hip geometry, using human genome-wide association study (GWAS) data from the GEFOS consortium. After correction for multiple testing, six TRPS1 SNPs were significantly associated with femoral neck BMD (P=0.0015-0.0019; adjusted P=0.038-0.048). We also found that three SNPs were highly associated with femoral neck width in women (rs10505257, P=8.6*10(-5), adjusted P=2.15*10(-3); rs7002384, P=5.5*10(-4), adjusted P=01.38*10(-2)). In conclusion, we demonstrated that combining association studies in humans with murine models provides an efficient strategy to identify new candidate genes for bone phenotypes. PMID- 22306697 TI - Ct-based finite element models can be used to estimate experimentally measured failure loads in the proximal femur. AB - The objective of this experimental finite element (FE) study was to assess the accuracy of a simulation model estimate of the experimentally measured fracture load of the proximal femur in a sideways fall. Sixty-one formalin-fixed cadaver femora (41 female and 20 male) aged 55-100 years (an average of 80 years) were scanned with a multi-detector CT scanner and were mechanically tested for failure in a sideways fall loading configuration. Twenty-one of these femurs were used for training purposes, and 40 femurs were used for validation purposes. The training set FE models were used to establish the strain threshold for the element failure criteria. Bi-linear elastoplastic FE analysis was performed based on the CT images. The validation set was used to estimate the fracture loads. The Drucker-Prager criterion was applied to determine the yielding and the maximum principal stress criteria and the minimum principal strain criteria for element failure in tension and in compression, respectively. The estimated fracture load values were highly correlated with the experimental data (r=0.931; p<0.001). The slope was 0.929, with an intercept of 258 N, which was not significantly different from 1 and 0, respectively. The study shows that it is possible to estimate the fracture load with relatively high accuracy in a sideways fall configuration by using the CT-based FE method. This method may therefore be applied for studying the biomechanical mechanisms of hip fractures. PMID- 22306698 TI - Sampling area selection for the assessment of goblet cell density from conjunctival impression cytology specimens. AB - PURPOSE: To assess the impact of using different sampling areas (fields of view) on the reliability of goblet cell density (GCD) estimates from conjunctival impression cytology (CIC) specimens from healthy individuals. METHODS: The CIC specimens were collected from the exposed nasal bulbar conjunctiva of 5 adult subjects (average age, 23 years) onto Biopore (Millicell) membranes and stained with Giemsa. A region from each of the specimens that contained abundant goblet cells was examined by light microscopy using a *40 magnification objective lens, *20 and *10 lenses, the images were enlarged, and the goblet cells were marked and counted. The GCD values per square millimeter were calculated and then the impact of counting between 10 to many and 10 to few goblet cells assessed. RESULTS: The mean GCD estimates at *400 magnification, *200, and *100 were 950 +/ 226, 620 +/- 154 and 471 +/- 158 cells per square millimeter, respectively; these values were statistically different (P<0.05). The GCD estimates could change by as much as +/-31.6%, +/-12.2%, and +/-4.2% for differences of +/-10 cells counted per image. CONCLUSIONS: As a result of variability in goblet cell distribution across CIC specimens, the estimates of GCD can be expected to be different according to the sampling area used for goblet cell counts. Furthermore, the use of a small sampling area (high power field of view) is likely to result in an unacceptably large uncertainty (variability) in the GCD estimates. PMID- 22306699 TI - Efficacy of thiolated eudragit microspheres as an oral vaccine delivery system to induce mucosal immunity against enterotoxigenic Escherichia coli in mice. AB - A vaccine delivery system based on thiolated eudragit microsphere (TEMS) was studied in vivo for its ability to elicit mucosal immunity against enterotoxigenic Escherichia coli (ETEC). Groups of mice were orally immunized with F4 or F18 fimbriae of ETEC and F4 or F18 loaded in TEMS. Mice that were orally administered with F4 or F18 loaded TEMS showed higher antigen-specific IgG antibody responses in serum and antigen-specific IgA in saliva and feces than mice that were immunized with antigens only. In addition, oral vaccination of F4 or F18 loaded TEMS resulted in higher numbers of IgG and IgA antigen-specific antibody secreting cells in the spleen, lamina propria, and Peyer's patches of immunized mice than other groups. Moreover, TEMS administration loaded with F4 or F18 induced mixed Th1 and Th2 type responses based on similarly increased levels of IgG1 and IgG2a. These results suggest that F4 or F18 loaded TEMS may be a promising candidate for an oral vaccine delivery system to elicit systemic and mucosal immunity against ETEC. PMID- 22306700 TI - Performance of cell-penetrating peptide-linked polymers physically mixed with poorly membrane-permeable molecules on cell membranes. AB - We are investigating a new class of penetration enhancers that enable poorly membrane-permeable molecules physically mixed with them to effectively penetrate cell membranes without their concomitant cellular uptake. Since we previously revealed that poly(N-vinylacetamide-co-acrylic acid) modified with d octaarginine, which is a typical cell-penetrating peptide, significantly enhanced the nasal absorption of insulin, we examined the performance of the polymers on cell membranes. When Caco-2 cells were incubated with 5(6)-carboxyfluorescein (CF) for 30 min, approximately 0.1% of applied CF was internalized into the cells. This poor membrane permeability was dramatically enhanced by d octaarginine-linked polymers; a 25-fold increase in the cellular uptake of CF was observed when the polymer concentration was adjusted to 0.2mg/mL. None of the individual components, for example, d-octaarginine, had any influence on CF uptake, demonstrating that only d-octaarginine anchored chemically to the polymeric platform enhanced the membrane permeation of CF. The polymer-induced CF uptake was consistently high even when the incubation time was extended to 120 min. Confocal laser scanning microphotographs of cells incubated with d octaarginine-linked polymers bearing rhodamine red demonstrated that the cell outline was stained with red fluorescence. The polymer-induced CF uptake was significantly suppressed by 5-(N-ethyl-N-isopropyl)amiloride, which is an inhibitor of macropinocytosis. Results indicated that d-octaarginine-linked polymers remained on the cell membrane and poorly membrane-permeable CF was continuously internalized into cells mainly via macropinocytosis repeated for the individual peptidyl branches in the polymer backbone. PMID- 22306701 TI - Influence of PEG in PEG-PLGA microspheres on particle properties and protein release. AB - The aim of the present study was to compare different commercial available types of Poly(d,l-lactide-co-glycolide) (PLGA), multiblock copolymers of PLGA and polyethylene gylcol (PEG) as well as blends of PLGA and PEG regarding the preparation of microparticles and the release behavior of encapsulated protein. Microspheres were prepared by the solvent evaporation technique using the same conditions for each formulation. The encapsulation rate of bovine serum albumin (BSA) was unaffected by the different polymer types, and the mean was 79+/-4%. Microspheres composed of blends of PLGA and PEG showed a porous structure, a higher specific surface area, an inhomogenous distribution of protein and a higher release rate of BSA than microspheres consisting of PLGA, whereas the release profiles were the same. The specific surface area of microparticle formulations composed of diblock copolymers was the highest with 8.57+/ 0.07m(2)/g emphasized by a highly porous, sponge-like structure. The triblock copolymer formulation revealed nearly spherical particles with a slightly uneven surface. Although the triblock copolymer consists of 10% PEG, the specific surface area was the lowest of all formulations. The rapid hydration due to PEG leads to a swollen matrix, which released the protein in a slow and continuous way. PMID- 22306703 TI - The definition and significance of Cucurbitacin B a STAT3 inhibitors. PMID- 22306702 TI - Mucins and toll-like receptors: kith and kin in infection and cancer. AB - Inflammation is underlying biological phenomenon common in infection and cancer. Mucins are glycoproteins which establish a physical barrier for undesirable entry of foreign materials through epithelial surfaces. A deregulated expression and an anomalous glycosylation pattern of mucins are known in large number of cancers. TLRs are class of receptors which recognize the molecular patterns of invading pathogens and activate complex inflammatory pathways to clear them. Aberrant expression of TLRs is observed in many cancers. A highly orchestrated action of mucins and TLRs is well evolved host defence mechanism; however, a link between the two in other non-infectious conditions has received less attention. Here we present an overview as to how mucins and TLRs give protection to the host and are deregulated during carcinogenesis. Further, we propose the possible mechanisms of cross-regulation between them in pathogenesis of cancer. As both mucins and TLRs are therapeutically important class of molecules, an understanding of the underlying molecular mechanisms connecting the two will open new avenues for the therapeutic targeting of cancer. PMID- 22306704 TI - Antiangiogenic agents as second-line therapy for advanced non-small cell lung cancer. AB - With the approval of the antiangiogenic antibody bevacizumab in non-small cell lung cancer (NSCLC) and other malignancies, the tumor vasculature has emerged as a worthwhile therapeutic target. Second-line therapies have the potential to improve overall survival and quality of life over best supportive care alone. Accordingly, phase II and phase III studies are actively evaluating antiangiogenic treatments in the second-line setting in NSCLC, and results are awaited. Such therapies include antiangiogenic antibodies, small molecule inhibitors, and vascular-disrupting agents. This review will present the current landscape of angiogenesis inhibition in NSCLC, focusing on use as second-line therapy. PMID- 22306705 TI - Characterization of circulating tumor cell aggregates identified in patients with epithelial tumors. AB - Circulating tumor cells (CTCs) have been implicated as a population of cells that may seed metastasis and venous thromboembolism (VTE), two major causes of mortality in cancer patients. Thus far, existing CTC detection technologies have been unable to reproducibly detect CTC aggregates in order to address what contribution CTC aggregates may make to metastasis or VTE. We report here an enrichment-free immunofluorescence detection method that can reproducibly detect and enumerate homotypic CTC aggregates in patient samples. We identified CTC aggregates in 43% of 86 patient samples. The fraction of CTC aggregation was investigated in blood draws from 24 breast, 14 non-small cell lung, 18 pancreatic, 15 prostate stage IV cancer patients and 15 normal blood donors. Both single CTCs and CTC aggregates were measured to determine whether differences exist in the physical characteristics of these two populations. Cells contained in CTC aggregates had less area and length, on average, than single CTCs. Nuclear to cytoplasmic ratios between single CTCs and CTC aggregates were similar. This detection method may assist future studies in determining which population of cells is more physically likely to contribute to metastasis and VTE. PMID- 22306706 TI - QSEN? What's QSEN? PMID- 22306707 TI - Impact of percent body fat on oral glucose tolerance testing: a cross-sectional study in 1512 obese children. AB - BACKGROUND: Although an association between insulin resistance (IR) and body adiposity has been reported in obese children, this relationship has not been studied as thoroughly as in adults. AIM: We evaluated the association between oral glucose tolerance testing (OGTT) and percent body fat (PBF) in a sample of 1512 obese children followed at a Pediatric Obesity Clinic. SUBJECTS AND METHODS: Six hundred and twenty-eight male and 884 female obese children aged 6 to 18 yr were consecutively enrolled into the study. OGTT was performed with administration of 1.75 g of glucose per kg of body weight (up to 75 g). PBF was estimated through bioelectrical impedance analysis (BIA) using a population- specific formula recently published by our group. Multivariable median regression was used to evaluate the association between 4 outcomes [glucose area under the curve (AUC), insulin AUC, insulin sensitivity index (ISI), and insulinogenic index (IGI)] and gender, age or pubertal status and PBF. RESULTS: Median PBF was 52% (range 26 to 70%). After correction for age and gender, a 10% increase of PBF was associated with a decrease of -0.50 [95% confidence interval (CI): -0.65 to 0.35] units of ISI and an increase of 0.15 units of IGI (95%CI 0.07 to 0.24). CONCLUSIONS: In obese children, PBF is inversely associated with IR and directly associated to beta-cell response as detected by OGTT. PMID- 22306709 TI - Laptop computers with Wi-Fi decrease human sperm motility and increase sperm DNA fragmentation. PMID- 22306710 TI - A tissue-engineered human endometrial stroma that responds to cues for secretory differentiation, decidualization, and menstruation. AB - OBJECTIVE: To show the responsiveness of tissue-engineered human endometrial stroma to combinations of hormones that mimic the secretory and menstrual phases of the cycle. DESIGN: In vitro experimental study. SETTING: University uterine biology research laboratory. PATIENT(S): None. INTERVENTION(S): Telomerase immortalized human endometrial stromal cells cultured in monolayers (two dimensional, 2D) or encapsulated in a collagen I hydrogel (three-dimensional, 3D) to create a simplified tissue-engineered stroma were exposed to hormone treatments mimicking early and late secretory phases, decidualization, and steroid withdrawal conditions to recapitulate menstruation. MAIN OUTCOME MEASURE(S): Morphologic and biochemical markers of decidualization and collagenase activity. RESULT(S): The 3D tissue can manifest changes in morphology and biochemical markers of decidualization similar to 2D culture and characteristic of endometrial stroma in vivo. Unlike 2D culture, the 3D tissue responded to steroid withdrawal by increased collagenase activity and tissue breakdown. CONCLUSION(S): Three-dimensional tissue-engineered endometrial stroma can mimic secretory and menstrual phases of the cycle and may be useful for studying uterine receptivity and menstruation in a physiological endocrine environment. PMID- 22306711 TI - Degradation of actin nucleators affects cortical polarity of aged mouse oocytes. AB - OBJECTIVE: To investigate the molecular mechanism of mouse oocyte polarity loss during aging. DESIGN: Experimental study. SETTING: Academic basic research laboratory. ANIMAL(S): Mice. INTERVENTION(S): Oocytes were collected 16 hours after injection of hCG and cultured in M16 medium for an additional 14 hours with or without caffeine. MAIN OUTCOME MEASURE(S): Expression and localizations of actin nucleators actin-related protein 2/3 complex, JMY, and WAVE2 were examined by immunofluorescence staining, and their messenger RNA levels were examined by real-time reverse transcription-polymerase chain reaction. RESULT(S): The protein and messenger RNA levels of actin-related protein 2/3 complex, JMY, and WAVE2 were decreased in aged oocytes, but the levels were normal in caffeine-treated aged oocytes. CONCLUSION(S): Our data indicated that the loss of oocyte polarity may be due to the degradation of actin nucleators in aged oocytes. PMID- 22306712 TI - Care pathways under the spotlight. PMID- 22306713 TI - To make the unusual usual: is there an imperative to discuss organ donation with palliative care patients? PMID- 22306714 TI - Pressure ulceration and palliative care: prevention, treatment, policy and outcomes. AB - Pressure ulcer development and management have particular significance in palliative and end-of-life care owing to the prevalence of mobility issues and the skin changes that can occur with ageing, chronic illness, and at the end of life. Hence, it is important for nurses working in palliative care to be vigilant for pressure ulcer development and to possess knowledge relating to the prevention and management of pressure ulceration. This article considers current UK policy regarding pressure ulcers, highlighting contradictions of relevance to patients requiring palliative care. It then provides a brief overview of pressure ulcer prevention, prescription, preservation, and palliation, highlighting areas of specific consideration to pressure ulcer care within palliative care. PMID- 22306715 TI - Constipation management in palliative care: treatments and the potential of independent nurse prescribing. AB - Constipation is a common symptom in palliative care patients that can generate considerable suffering owing to both the inherent physical discomfort and the attendant psychological issues such as embarrassment. This article considers the management of constipation for palliative care patients, including the importance of the patient's own definition of their problem, the need for thorough and frequent assessment, established treatment options, and the challenges that nurses may face. It provides a simple algorithm to assist in the management process, and also looks at the current strength of the evidence base for two more recent therapies. Finally, it examines the potential of the independent nurse prescriber (INP) for constipation management in the UK, using a brief case study to illustrate a commonly experienced constipation management scenario for the INP in the community setting. PMID- 22306716 TI - Critical reflections on end-of-life care for people with intellectual disabilities: a single case study approach. AB - People with intellectual disabilities (ID) are enjoying increasing longevity, but are simultaneously having to cope with the additional health problems associated with ageing. Even though people with ID are reported to have worse health than the rest of the population, resulting in greater health-care needs, they also have poorer health care than the average person, including including-end-of-life care. The aim of this paper is to explore the challenges to providing effective end-of-life care for a person with an ID by using critical reflection from a nursing care perspective on an illustrative case study. Death never occurs in a vacuum but rather occurs in a social context, and the social context here was crucial to providing appropriate end-of-life care. It is hoped that the paper will promote discussion both around end-of-life care generally and in relation to this marginalized population. PMID- 22306717 TI - End-of-life care considerations for gay, lesbian, bisexual, and transgender individuals. AB - Negative social attitudes, discrimination, and homophobia affect gay, lesbian, bisexual, and transgender (GLBT) individuals during their lifetimes. These experiences can affect how these individuals access health services and interact with health professionals, resulting in adverse outcomes compared with their heterosexual counterparts. End-of-life experiences can also be shaped by these factors. There are implications for health professionals in terms of equity of access to targeted health care, preventive screening, and visibility in policy, as well as in principles of inclusiveness, dignity and respect, and competence in care. This article takes a brief look at some of the issues specific to the end of-life care of GLBT individuals, using a case study as an illustrative example. Holistic care at the end of life is a familiar concept to palliative care nurses, but it is important to place greater emphasis on considering competence in aspects of care relating to sexuality. PMID- 22306718 TI - Gender differences in 1-year survival rates after weight loss in people with idiopathic Parkinson's disease. AB - BACKGROUND: Under-nutrition is a recognized non-motor symptom of Parkinson's disease (PD). The aim of this retrospective study was to conduct an audit of recorded weight loss prior to death in people with PD and to identify whether weight loss was a predictor of death. METHODS: An audit of the medical records of people with PD was conducted. Patients were included if they were under the care of the North Tyneside General Hospital PD team, had a diagnosis of idiopathic PD, and died between 1 January 2008 and 31 December 2010. To assess whether there was a significant association between clinically significant weight loss and mortality, values of 5% and 10% weight loss from earliest available post diagnosis baseline assessment were chosen as cut-offs. RESULTS: Data were available on 55 patients. Although females were more likely to have 10% weight loss than men, the difference was not significant. The odds of a female with weight loss surviving beyond 1 year were 23.4 (95% confidence interval (CI) 3.9 139.9) times better than those of a male for 5% weight loss and 10.0 (95% CI 1.8 55.6) times better than those of a male for 10% weight loss. These results were significant. CONCLUSIONS: Outcomes for males with PD who have clinically important weight loss are poorer than for females. Nurses and other health workers should be aware of the need to monitor weight in people with PD. PMID- 22306719 TI - Nurses' nonverbal methods of communicating with patients in the terminal phase. AB - AIM: The aim of this study was to ascertain what methods of communication nurses use during interactions with patients nearing the end of their lives, with a particular focus on nonverbal communication. METHODOLOGY: A questionnaire containing 24 questions was completed by 95 nurses working in one of five hospices in Poland. RESULTS: A total of 48% of the sample reported frequently using nonverbal communication consciously and with a certain aim, and a further 37 (39%) reported that they sometimes use it. The sample's responses indicate that for patients the best form of touch is holding hands. In addition, 63% of the respondents stated that they had been educated in communicating with palliative care patients, but only 56% thought that nurses' communication knowledge and skills were satisfactory, and 50% would like to undergo training in communication skills specific to palliative care. CONCLUSION: Most nurses are aware of the importance of nonverbal communication to their interactions with palliative care patients, but a substantial proportion think that they need to be better educated in theoretical and practical aspects of communication. PMID- 22306721 TI - Cost effectiveness in specialist palliative care. PMID- 22306724 TI - Sometimes it's all about the question. PMID- 22306723 TI - The sialotranscriptome of Antricola delacruzi female ticks is compatible with non hematophagous behavior and an alternative source of food. AB - The hosts for Antricola delacruzi ticks are insectivorous, cave-dwelling bats on which only larvae are found. The mouthparts of nymphal and adult A. delacruzi are compatible with scavenging feeding because the hypostome is small and toothless. How a single blood meal of a larva provides energy for several molts as well as for oviposition by females is not known. Adults of A. delacruzi possibly feed upon an unknown food source in bat guano, a substrate on which nymphal and adult stages are always found. Guano produced by insectivorous bats contains twice the amount of protein and 60 times the amount of iron as beef. In addition, bacteria and chitin-rich fungi proliferate on guano. Comparative data on the transcriptome of the salivary glands of A. delacruzi is nonexistent and would help to understand the physiological adaptations of salivary glands that accompany different sources of food as well as the steps taken by the Acari toward haematophagy, believed to have evolved from scavenging dead animals. Annotation of the transcriptome of salivary glands from female instars of A. delacruzi collected on guano categorized 5.7% of the clusters of expressed genes as putative secreted proteins. They included abundantly expressed TIL-domain containing proteins (possible anti-microbials), an abundantly expressed protein similar to a serum amyloid found in the sialotranscriptomes of Ornithodoros spp., a savignygrin, a family of mucin/peritrophin/cuticle-like proteins, anti microbials and an HIV envelope-like glycoprotein also found in soft ticks. When comparing the transcriptome of A. delacruzi with those of blood-feeding female soft and hard ticks some notable differences were observed; they consisted of the following transcripts over- or under-represented or absent in the sialotranscriptome of A. delacruzi that may reflect its source of food: ferritin, mucins with chitin-binding domains and TIL-domain-containing proteins versus lipocalins, basic tail proteins, metalloproteases, glycine-rich proteins and Kunitz protease inhibitors, respectively. PMID- 22306725 TI - Practical considerations for recognizing and managing severe irritable bowel syndrome. AB - Irritable bowel syndrome (IBS) is a common disorder characterized by abdominal pain or discomfort and altered bowel habit (chronic or recurrent diarrhea, constipation, or both) that occurs more frequently in women than in men. Severe IBS may be underrecognized and inadequately managed in clinical practice. Although no consensus definition for "severe IBS" exists, patients may be categorized as having severe illness if they show an insufficient response to conventional treatments or if their functionality or quality of life is impaired as a result of their IBS symptoms. Nurses can be an important resource in optimizing the evaluation and treatment of these patients. Nursing assessments that delineate predominant symptoms and the history and nature of prior interventions (e.g., lifestyle changes, over-the-counter or prescription medication trials, psychotherapy, alternative treatments) and subsequent responses are important when advising patients and participating in the management of their IBS. Likewise, the nurse's assessment should include a history of symptom severity and impact on daily functioning, as these elements are important to choosing therapy. The nurse-patient dialogue should also include a description of available treatment options and the benefits and risks associated with each. By maintaining such a dialogue, nurses can hasten IBS recognition, improve management, limit the negative consequences of this common disorder, and improve overall treatment outcomes in this population. PMID- 22306727 TI - Difficulties in taking aminosalicylates for patients with ulcerative colitis. AB - Aminosalicylates are effective in inducing remission and are also useful in preventing relapse of ulcerative colitis (UC); however, previous studies have reported a 30%-45% rate of nonadherence to prescribed medication among UC patients. Enumerating and conceptualizing the difficulties in taking aminosalicylates enable us to assess and support patients more effectively. The aim of this study was to investigate the difficulties in taking aminosalicylates among Japanese UC patients and explore factors related to these difficulties. Outpatients with UC (n = 242) completed a questionnaire supported by a semistructured interview on the basis of a literature review. Twelve items about difficulties in taking aminosalicylates were processed by factor analysis and the related factors regarding difficulties were analyzed. The following three independent domains were identified: Domain 1: diminished sense of priority for medication; Domain 2: concern about side effects; and Domain 3: burden of taking the prescribed drug. Factors related to the difficulties in taking aminosalicylates included the disease state, psychosocial factors, and demographic characteristic variables. On the basis of the results, we recommend the creation and validation of a program aimed at decreasing the difficulties in taking aminosalicylates. PMID- 22306728 TI - Enhancing bowel preparation for colonoscopy: an integrative review. AB - Colorectal cancer is the third most common cancer and second leading cause of cancer-related deaths in the United States. Currently, colonoscopy is considered the gold standard to detect colorectal cancer. Poor bowel preparation in patients undergoing colonoscopy compromises the quality and efficacy of this procedure, affecting patient outcomes and increasing overall costs. With up to 25% of patients undergoing colonoscopy having poor bowel preparation, interventions to enhance the quality of bowel preparations are vital to improving clinical practice. Through an extensive review of the current literature, split-dose bowel preparation regimens appear to be the most well-supported and plausible intervention for meaningful change in efforts to enhance bowel preparation. Several studies of high quality and strength have drawn consistent conclusions that split-dose bowel preparations result in significantly better bowel cleansing than traditional day-prior bowel preparation regimens. Strengths, limitations, gaps in the current literature, and areas for future research are identified, which can help to direct future studies needed to strengthen the evidence and determine further practice initiatives to address the problem of poor bowel preparation for colonoscopy. PMID- 22306729 TI - Diverticulitis: the relationship between body mass index and disease location, recurrence, and complications. AB - The purpose of this study is to examine the relationship between body mass index (BMI) and recurrent diverticulitis, complication rate, and location of disease in an ambulatory population. A retrospective chart review was performed using patients with computed tomography-documented diverticulitis in a New York outpatient gastroenterology practice. Total episodes, location of disease, complications, and BMI and age at first episode were recorded. A random control group was formed using patients with diverticulosis from the same practice. Controls' BMI and age at last colonoscopy were recorded. Descriptive statistics and Student's t test were used with alpha set at p < .05. Patients with diverticulitis were significantly more overweight than patients with diverticulosis (p < .05); however, among ambulatory patients with diverticulitis, there was no significant difference in the BMI of patients with a single episode when compared with those with recurrent disease. Furthermore, there was no association between BMI and complication rate or location of disease. PMID- 22306730 TI - Ulcerative colitis from patients' viewpoint: a review of two Internet surveys. AB - Ulcerative colitis negatively impacts patients' quality of life, but little is known about which aspects of patients' lives are affected, how patients' perceptions compare with patients with other chronic conditions, and how these perceptions compare with those of gastroenterologists. This review discusses two recent Internet surveys: (1) the Ulcerative Colitis: New Observations on Remission Management And Lifestyle (UC:NORMAL) and (2) the Crohn's and Colitis Foundation of America studies. The surveys revealed that the major impact ulcerative colitis has on patients includes frequent disease manifestations, a substantial psychological burden, and disruption to daily activities. This was more evident in patients with ulcerative colitis than those with migraine, asthma, or rheumatoid arthritis. Physicians' perceptions were considerably different from those of patients, as physicians believed that the disease had a lesser impact on patient quality of life. Furthermore, patients and physicians also identified nonadherence to prescribed medication as a major concern in the treatment of ulcerative colitis. Improved communication and education is needed to address nonadherence and poor health related quality of life in patients living with ulcerative colitis. The influence of Advanced Practice Registered Nurses on physicians, nurses, and patients may help improve adherence and long term disease outcomes, including patients' health related quality of life. The nurse practitioner, working with both patients who have ulcerative colitis and the physicians who care for these patients, is uniquely placed to address these needs. PMID- 22306731 TI - An unusual presentation of celiac disease in a middle-aged man treated for hypertension: a case report. PMID- 22306732 TI - Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass. AB - Aging reduces the number of mesenchymal stem cells (MSCs) that can differentiate into osteoblasts in the bone marrow, which leads to impairment of osteogenesis. However, if MSCs could be directed toward osteogenic differentiation, they could be a viable therapeutic option for bone regeneration. We have developed a method to direct MSCs to the bone surface by attaching a synthetic high-affinity and specific peptidomimetic ligand (LLP2A) against integrin alpha4beta1 on the MSC surface to a bisphosphonate (alendronate, Ale) that has a high affinity for bone. LLP2A-Ale induced MSC migration and osteogenic differentiation in vitro. A single intravenous injection of LLP2A-Ale increased trabecular bone formation and bone mass in both xenotransplantation studies and in immunocompetent mice. Additionally, LLP2A-Ale prevented trabecular bone loss after peak bone acquisition was achieved or as a result of estrogen deficiency. These results provide proof of principle that LLP2A-Ale can direct MSCs to the bone to form new bone and increase bone strength. PMID- 22306733 TI - Activin-like kinase 3 is important for kidney regeneration and reversal of fibrosis. AB - Molecules associated with the transforming growth factor beta (TGF-beta) superfamily, such as bone morphogenic proteins (BMPs) and TGF-beta, are key regulators of inflammation, apoptosis and cellular transitions. Here we show that the BMP receptor activin-like kinase 3 (Alk3) is elevated early in diseased kidneys after injury. We also found that its deletion in the tubular epithelium leads to enhanced TGF-beta1-Smad family member 3 (Smad3) signaling, epithelial damage and fibrosis, suggesting a protective role for Alk3-mediated signaling in the kidney. A structure-function analysis of the BMP-Alk3-BMP receptor, type 2 (BMPR2) ligand-receptor complex, along with synthetic organic chemistry, led us to construct a library of small peptide agonists of BMP signaling that function through the Alk3 receptor. One such peptide agonist, THR-123, suppressed inflammation, apoptosis and the epithelial-to-mesenchymal transition program and reversed established fibrosis in five mouse models of acute and chronic renal injury. THR-123 acts specifically through Alk3 signaling, as mice with a targeted deletion for Alk3 in their tubular epithelium did not respond to therapy with THR 123. Combining THR-123 and the angiotensin-converting enzyme inhibitor captopril had an additive therapeutic benefit in controlling renal fibrosis. Our studies show that BMP signaling agonists constitute a new line of therapeutic agents with potential utility in the clinic to induce regeneration, repair and reverse established fibrosis. PMID- 22306734 TI - Nitric oxide-releasing nanoparticles accelerate wound healing by promoting fibroblast migration and collagen deposition. AB - Wound healing is a complex process that involves coordinated interactions between diverse immunological and biological systems. Long-term wounds remain a challenging clinical problem, affecting approximately 6 million patients per year, with a high economic impact. To exacerbate the problem, these wounds render the individual susceptible to life-threatening microbial infections. Because current therapeutic strategies have proved suboptimal, it is imperative to focus on new therapeutic approaches and the development of technologies for both short- and long-term wound management. In recent years, nitric oxide (NO) has emerged as a critical molecule in wound healing, with NO levels increasing rapidly after skin damage and gradually decreasing as the healing process progresses. In this study, we examined the effects of a novel NO-releasing nanoparticle technology on wound healing in mice. The results show that the NO nanoparticles (NO-np) significantly accelerated wound healing. NO-np modified leukocyte migration and increased tumor growth factor-beta production in the wound area, which subsequently promoted angiogenesis to enhance the healing process. By using human dermal fibroblasts, we demonstrate that NO-np increased fibroblast migration and collagen deposition in wounded tissue. Together, these data show that NO releasing nanoparticles have the ability to modulate and accelerate wound healing in a pleiotropic manner. PMID- 22306735 TI - Long-term survival after high-dose chemotherapy followed by peripheral stem cell rescue for high-risk, locally advanced/inflammatory, and metastatic breast cancer. AB - Patients with high-risk locally advanced/inflammatory and oligometastatic (<=3 sites) breast cancer frequently relapse or experience early progression. High dose chemotherapy combined with peripheral stem cell rescue may prolong progression-free survival/relapse-free survival (PFS/RFS) and overall survival (OS). In this study, patients initiated high-dose chemotherapy with STAMP-V (carboplatin, thiotepa, and cyclophosphamide), ACT (doxorubicin, paclitaxel, and cyclophosphamide), or tandem melphalan and STAMP-V. Eighty-six patients were diagnosed with locally advanced/inflammatory (17 inflammatory) breast cancer, and 12 were diagnosed with oligometastatic breast cancer. Median follow-up was 84 months (range, 6-136 months) for patients with locally advanced cancer and 40 months (range, 24-62 months) for those with metastatic cancer. In the patients with locally advanced cancer, 5-year RFS and OS were 53% (95% CI, 41%-63%) and 71% (95% CI, 60%-80%), respectively, hormone receptors were positive in 74%, and HER2 overexpression was seen in 23%. In multivariate analysis, hormone receptor positive disease and lower stage were associated with better 5-year RFS (60% for ER [estrogen receptor]/PR [progesterone receptor]-positive versus 30% for ER/PR negative; P < .01) and OS (83% for ER/PR-positive versus 38% for ER/PR-negative; P < .001). In the patients with metastatic cancer, 3-year PFS and OS were 49% (95% CI, 19%-73%) and 73% (95% CI, 38%-91%), respectively. The favorable long term RFS/PFS and OS for high-dose chemotherapy with peripheral stem cell rescue in this selected patient population reflect the relative safety of the procedure and warrant validation in defined subgroups through prospective, randomized, multi-institutional trials. PMID- 22306736 TI - Cytometric comparisons between circulating tumor cells from prostate cancer patients and the prostate-tumor-derived LNCaP cell line. AB - Many important experiments in cancer research are initiated with cell line data analysis due to the ease of accessibility and utilization. Recently, the ability to capture and characterize circulating tumor cells (CTCs) has become more prevalent in the research setting. This ability to detect, isolate and analyze CTCs allows us to directly compare specific protein expression levels found in patient CTCs to cell lines. In this study, we use immunocytochemistry to compare the protein expression levels of total cytokeratin (CK) and androgen receptor (AR) in CTCs and cell lines from patients with prostate cancer to determine what translational insights might be gained through the use of cell line data. A non enrichment CTC detection assay enables us to compare cytometric features and relative expression levels of CK and AR by indirect immunofluorescence from prostate cancer patients against the prostate cancer cell line LNCaP. We measured physical characteristics of these two groups and observed significant differences in cell size, fluorescence intensity and nuclear to cytoplasmic ratio. We hope that these experiments will initiate a foundation to allow cell line data to be compared against characteristics of primary cells from patients. PMID- 22306737 TI - Crystal structure of p44, a constitutively active splice variant of visual arrestin. AB - Visual arrestin specifically binds to photoactivated and phosphorylated rhodopsin and inactivates phototransduction. In contrast, the p44 splice variant can terminate phototransduction by binding to nonphosphorylated light-activated rhodopsin. Here we report the crystal structure of bovine p44 at a resolution of 1.85 A. Compared to native arrestin, the p44 structure reveals significant differences in regions crucial for receptor binding, namely flexible loop V-VI and polar core regions. Additionally, electrostatic potential is remarkably positive on the N-domain and the C-domain. The p44 structure represents an active conformation that serves as a model to explain the 'constitutive activity' found in arrestin variants. PMID- 22306738 TI - Disease-associated polyglutamine stretches in monomeric huntingtin adopt a compact structure. AB - Abnormal polyglutamine (polyQ) tracts are the only common feature in nine proteins that each cause a dominant neurodegenerative disorder. In Huntington's disease, tracts longer than 36 glutamines in the protein huntingtin (htt) cause degeneration. In situ, monoclonal antibody 3B5H10 binds to different htt fragments in neurons in proportion to their toxicity. Here, we determined the structure of 3B5H10 Fab to 1.9 A resolution by X-ray crystallography. Modeling demonstrates that the paratope forms a groove suitable for binding two beta-rich polyQ strands. Using small-angle X-ray scattering, we confirmed that the polyQ epitope recognized by 3B5H10 is a compact two-stranded hairpin within monomeric htt and is abundant in htt fragments unbound to antibody. Thus, disease associated polyQ stretches preferentially adopt compact conformations. Since 3B5H10 binding predicts degeneration, this compact polyQ structure may be neurotoxic. PMID- 22306740 TI - Antifreeze protein from freeze-tolerant grass has a beta-roll fold with an irregularly structured ice-binding site. AB - The grass Lolium perenne produces an ice-binding protein (LpIBP) that helps this perennial tolerate freezing by inhibiting the recrystallization of ice. Ice binding proteins (IBPs) are also produced by freeze-avoiding organisms to halt the growth of ice and are better known as antifreeze proteins (AFPs). To examine the structural basis for the different roles of these two IBP types, we have solved the first crystal structure of a plant IBP. The 118-residue LpIBP folds as a novel left-handed beta-roll with eight 14- or 15-residue coils and is stabilized by a small hydrophobic core and two internal Asn ladders. The ice binding site (IBS) is formed by a flat beta-sheet on one surface of the beta roll. We show that LpIBP binds to both the basal and primary-prism planes of ice, which is the hallmark of hyperactive AFPs. However, the antifreeze activity of LpIBP is less than 10% of that measured for those hyperactive AFPs with convergently evolved beta-solenoid structures. Whereas these hyperactive AFPs have two rows of aligned Thr residues on their IBS, the equivalent arrays in LpIBP are populated by a mixture of Thr, Ser and Val with several side-chain conformations. Substitution of Ser or Val for Thr on the IBS of a hyperactive AFP reduced its antifreeze activity. LpIBP may have evolved an IBS that has low antifreeze activity to avoid damage from rapid ice growth that occurs when temperatures exceed the capacity of AFPs to block ice growth while retaining the ability to inhibit ice recrystallization. PMID- 22306739 TI - Modulation of the interaction between neurotensin receptor NTS1 and Gq protein by lipid. AB - Membrane lipids have been implicated to influence the activity of G-protein coupled receptors (GPCRs). Almost all of our knowledge on the role of lipids on GPCR and G protein function comes from work on the visual pigment rhodopsin and its G protein transducin, which reside in a highly specialized membrane environment. Thus, insight gained from rhodopsin signaling may not be simply translated to other nonvisual GPCRs. Here, we investigated the effect of lipid head group charges on the signal transduction properties of the class A GPCR neurotensin (NT) receptor 1 (NTS1) under defined experimental conditions, using self-assembled phospholipid nanodiscs prepared with the zwitter-ionic lipid 1 palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), the negatively charged 1 palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG), or a POPC/POPG mixture. A combination of dynamic light scattering and sedimentation velocity showed that NTS1 was monomeric in POPC-, POPC/POPG-, and POPG-nanodiscs. Binding of the agonist NT to NTS1 occurred with similar affinities and was essentially unaffected by the phospholipid composition. In contrast, Gq protein coupling to NTS1 in various lipid nanodiscs was significantly different, and the apparent affinity of Galphaq and Gbeta(1)gamma(1) to activated NTS1 increased with increasing POPG content. NTS1-catalyzed GDP/GTPgammaS nucleotide exchange at Galphaq in the presence of Gbeta(1)gamma(1) and NT was crucially affected by the lipid type, with exchange rates higher by 1 or 2 orders of magnitude in POPC/POPG and POPG-nanodiscs, respectively, compared to POPC-nanodiscs. Our data demonstrate that negatively charged lipids in the immediate vicinity of a nonvisual GPCR modulate the G-protein-coupling step. PMID- 22306741 TI - DLK2 is a transcriptional target of KLF4 in the early stages of adipogenesis. AB - The epidermal growth factor-like protein DLK2, highly homologous to DLK1, has been identified as a modulator of adipogenesis in vitro. Knocking down Dlk2 expression prevents adipogenesis of 3T3-L1 cells but enhances that of the mesenchymal cell line C3H10T1/2. The expression of Dlk2 shows two peaks along this differentiation process: the first one, in response to 3-isobutyl-1 methylxanthine (IBMX) and dexamethasone (Dex), and the second, shortly after exposure to insulin. Nothing is known about the transcriptional regulation of Dlk2 during adipogenesis. Here, we report that, during early adipogenesis of 3T3 L1 cells, Dlk2 expression is controlled independently by IBMX and Dex. We also show that KLF4, a transcription factor critical for the control of early adipogenesis, binds directly to the Dlk2 promoter and increases Dlk2 expression in response to IBMX. Overexpression of KLF4 leads to an increase in DLK2 expression levels, whereas KLF4 knockdown downregulates the transcriptional activity of the Dlk2 promoter. Finally, we demonstrate that KLF4 regulates the basal expression of Dlk2 in C3H10T1/2 cells, and it is required for the adipogenic differentiation of those cells. These results indicate that KLF4 mediates the transcriptional regulation of Dlk2 in response to IBMX during the early stages of adipogenesis. PMID- 22306742 TI - A novel protein refolding protocol for the solubilization and purification of recombinant peptidoglycan-associated lipoprotein from Xylella fastidiosa overexpressed in Escherichia coli. AB - Xylella fastidiosa is a Gram-negative xylem-limited plant pathogenic bacterium responsible for several economically important crop diseases. Here, we present a novel and efficient protein refolding protocol for the solubilization and purification of recombinant X. fastidiosa peptidoglycan-associated lipoprotein (XfPal). Pal is an outer membrane protein that plays important roles in maintaining the integrity of the cell envelope and in bacterial pathogenicity. Because Pal has a highly hydrophobic N-terminal domain, the heterologous expression studies necessary for structural and functional protein characterization are laborious once the recombinant protein is present in inclusion bodies. Our protocol based on the denaturation of the XfPal-enriched inclusion bodies with 8M urea followed by buffer-exchange steps via dialysis proved effective for the solubilization and subsequent purification of XfPal, allowing us to obtain a large amount of relatively pure and folded protein. In addition, XfPal was biochemically and functionally characterized. The method for purification reported herein is valuable for further research on the three dimensional structure and function of Pal and other outer membrane proteins and can contribute to a better understanding of the role of these proteins in bacterial pathogenicity, especially with regard to the plant pathogen X. fastidiosa. PMID- 22306743 TI - Expression of an Acidothermus cellulolyticus endoglucanase in transgenic rice seeds. AB - The thermostable endo-1,4-beta-glucanase (E1) from Acidothermus cellulolyticus, is a useful enzyme for commercial hydrolysis of cellulose into glucose. A codon optimized synthetic gene encoding this enzyme was transformed into rice (Oryza sativa L. ssp. japonica) under the control of the rice seed storage protein Gt1 promoter. The transgenic line C19 was identified as the one with the highest endoglucanase activity among the total of 36 independent transgenic lines obtained. The cellulase activity in the C19 seeds was estimated at about 830U/g of dried seeds using CMC as substrate. The enzymes produced in the seeds had an optimum pH of 5.0 and optimum temperature of 80 degrees C, which is similar to the enzymes produced by the native bacterium host. This study demonstrates that the transgenic rice seeds could be used as a bioreactor for production of enzymes for cellulosic biomass conversion. PMID- 22306744 TI - The structural characteristics of human preprotein translocase of the inner mitochondrial membrane Tim23: implications for its physiological activities. AB - The preprotein translocase of the inner mitochondrial membrane (TIM23 complex) is the main entry gate for proteins of the matrix and the inner membrane. Tim23 forms a pore for preprotein transportation in TIM23 complex, which spans the inner membrane with transmembrane segments and exposes a hydrophilic domain in the intermembrane space. In this study, we expressed and purified the intermembrane space (IMS) domain of human Tim23 (Tim23(IMS)). The far-UV CD spectra of Tim23(IMS) in native and denatured states revealed that the protein has a limited secondary structure and a not well-defined tertiary packing. Its Stokes radius was larger than both its expected size as a folded globular protein and the size determined by size exclusion chromatography. A large increase in 8 anilino-1-naphthalene-sulfonate (ANS) fluorescence (>50-fold) was observed, indicating that hydrophobic clusters are exposed at its surface. And GlobPlot/DisEMBL program predicted that the protein is in a loose folding state. We therefore conclude that, the non-bound hydrophilic domain of the human Tim23 is in a molten globule configuration with marginal stability. Furthermore, size exclusion chromatography and sedimentation equilibrium analysis showed that Tim23(IMS) exists as a dimer. And the results, showed by ANS binding and fluorescence quenching, indicated that a pH-dependent conformational change of Tim23(IMS) occurs, and at pH 4 and 3, it forms a compact structure. PMID- 22306745 TI - Effects of protein kinase A and G inhibitors on hippocampal cholinergic markers expressions in rolipram- and sildenafil-induced spatial memory improvement. AB - Although there are number of studies showing that phosphodiesterase (PDE) 4 and 5 inhibitors affect different kinds of memory, their effects on spatial memory consolidation in conjunction with the cholinergic activity in the hippocampus have not been studied before. In the present study firstly, rats were evaluated for the effects of different doses of the PDE4 inhibitor rolipram and the PDE5 inhibitor sildenafil on spatial memory consolidation in the water maze task. Rolipram or sildenafil was daily administered intraperitoneally 3 or 0 h after the last trial of training, respectively. Then in a separate related experiment the effect of the most efficient doses of rolipram or sildenafil accompanied by an intrahippocampally injected protein kinase A (PKA) or protein kinase G (PKG) inhibitor, respectively, was examined. Finally for determination of the hippocampal cholinergic activity the protein expression of hippocampal vesicular acetylcholine transporter (VAChT) and cholineacetyltransferase (ChAT) was measured. Rolipram at 0.03 mg/kg as well as sildenafil at 3 mg/kg increased spatial memory and their enhancing effect was completely blocked following inhibition of PKA and PKG, respectively. Furthermore, none of the treatments had a significant effect on the hippocampal ChAT and VAChT levels. Our data showed that rolipram and sildenafil enhanced spatial memory consolidation in an inverted U-shaped dose-response curve. This effect is dependent on the activity of cAMP/PKA- and cGMP/PKG-mediated pathways, respectively in the hippocampus. However, we did not find evidence for a chronic increase of cholinergic activity in the observed PDE inhibitor-induced memory improvement. PMID- 22306746 TI - Lamotrigine treatment reverses depressive-like behavior and alters BDNF levels in the brains of maternally deprived adult rats. AB - Lamotrigine is an anticonvulsant and has an antiglutamatergic action, which may contribute to its antidepressant effects, since glutamate has been linked to depression. The purpose of the present study was to investigate the behavioral and molecular effects of lamotrigine treatment in maternally deprived rats. To this aim, deprived and non-deprived male rats were treated with lamotrigine (20 mg/kg) once a day for 14 days during their adult phase. Their behavior was then assessed in the forced swimming and open field tests. In addition to this, the BDNF and NGF levels were assessed in the prefrontal cortex, hippocampus and amygdala. In the course of this study we demonstrated that maternally deprived rats treated with saline and lamotrigine showed an increase in their immobility time and a decrease in the climbing and swimming times when compared with non deprived rats treated with saline alone. Treatment with lamotrigine reversed the increase in the immobility time in the deprived rats. The BDNF levels were decreased in the amygdala in deprived rats treated with saline, and treatment with lamotrigine reversed this decrease. The NGF levels were decreased in the hippocampus in deprived rats treated with saline, but treatment with lamotrigine did not reverse this decrease. In conclusion, lamotrigine showed antidepressant effects in the forced swimming test, and it presented positive effects on the BDNF protein levels in the amygdala of maternally deprived rats. PMID- 22306747 TI - Acetic acid- and phenyl-p-benzoquinone-induced overt pain-like behavior depends on spinal activation of MAP kinases, PI(3)K and microglia in mice. AB - The acetic acid and phenyl-p-benzoquinone are easy and fast screening models to access the activity of novel candidates as analgesic drugs and their mechanisms. These models induce a characteristic and quantifiable overt pain-like behavior described as writhing response or abdominal contortions. The knowledge of the mechanisms involved in the chosen model is a crucial step forward demonstrating the mechanisms that the candidate drug would inhibit because the mechanisms triggered in that model will be addressed. Herein, it was investigated the role of spinal mitogen-activated protein (MAP) kinases ERK (extracellular signal regulated kinase), JNK (Jun N-terminal Kinase) and p38, PI(3)K (phosphatidylinositol 3-kinase) and microglia in the writhing response induced by acetic acid and phenyl-p-benzoquinone, and flinch induced by formalin in mice. Acetic acid and phenyl-p-benzoquinone induced significant writhing response over 20 min. The nociceptive response in these models were significantly and in a dose dependent manner reduced by intrathecal pre-treatment with ERK (PD98059), JNK (SB600125), p38 (SB202190) or PI(3)K (wortmannin) inhibitors. Furthermore, the co treatment with MAP kinase and PI(3)K inhibitors, at doses that were ineffective as single treatment, significantly inhibited acetic acid- and phenyl-p benzoquinone-induced nociception. The treatment with microglia inhibitors minocycline and fluorocitrate also diminished the nociceptive response. Similar results were obtained in the formalin test. Concluding, MAP kinases and PI(3)K are important spinal signaling kinases in acetic acid and phenyl-p-benzoquinone models of overt pain-like behavior and there is also activation of spinal microglia indicating that it is also important to determine whether drugs tested in these models also modulate such spinal mechanisms. PMID- 22306748 TI - Prenatal exposure to tobacco extract containing nicotinic alkaloids produces morphological and behavioral changes in newborn rats. AB - Tobacco exposure is not only a health concern for adults but has also been shown to exert deleterious effects on the health of the fetus, newborn, child, and adolescent. Decreased cognitive function, lower Intellectual Quotient (IQ) and deficits in learning and memory in children have been associated with maternal smoking during pregnancy. In this study, we have studied the effect of a tobacco plant extract on the growth and development in the rat. The extract contained relative proportions of alkaloids, including nicotine, purified by chemical separation. Pregnant rats received oral doses of either control (NaCl) or tobacco extract during the entire gestational period. Offspring length and body weight were measured. Each day, the offspring were observed for the following physical parameters: hair growth, incisor eruption and eye opening. The day of appearance of these developments was recorded. Before weaning, the offspring were examined to test their cliff avoidance response (6 postnatal day (PN)), surface righting reflex (05, 07, 13 postnatal day), swimming development (10, 12 postnatal day), negative geotaxis response (7,9,13 and 17 postnatal day) and jumping down choice cage (15, 17 postnatal day). Administration of tobacco extract to dams during the entire gestation period affects behavior and development in pups. The observed effects were a delay in opening eyes, incisor eruption and hair appearance, behavioral developments and an alteration in the rate of success behavior. However, in the jumping down choice cage test there was no difference compared to control animals. The results suggest that tobacco extract has a significant effect on the development of behavioral patterns, orientation and motor coordination and function. They also suggest significant growth retardation and teratogenic effects. PMID- 22306749 TI - Influence of elevated temperatures on the immune response of abalone, Haliotis rubra. AB - Elevated water temperature can act as a stressor impacting the immune responses of molluscs, potentially increasing their susceptibility to microbial infections. Abalone are commercially important marine molluscs that have recently experienced disease outbreaks caused by a herpesvirus and Vibrio bacteria. Sampling of wild caught Haliotis rubra showed a significant correlation between water temperature and both antiviral and antibacterial activity, with higher activity in summer than in winter months. However, antibacterial activity was compromised in favour of antiviral activity as the water temperatures peaked in summer. A controlled laboratory experiment was then used to investigate several immune responses of H. rubra, including total haemocyte count (THC), stimulated superoxide anion production (SO), antiviral activity against a model herpesvirus, herpes simplex virus type 1 and antibacterial activity against a representative pathogenic bacterium, Vibrio anguillarum, over one week after raising water temperature from 18 to 21 or 24 degrees C. THC and SO increased at day 1 and then dropped back to control levels by days 3 and 7. By comparison, the humoural immune parameters showed a delayed response with antibacterial and antiviral activity significantly increasing on days 3 and 7, respectively. Consistent with the field study, antibacterial activity became significantly depressed after prolonged exposure to elevated temperatures. A principal components analysis on the combined immune parameters showed a negative correlation between antiviral and antibacterial activity. SO was positively correlated to THC and neither of these cellular parameters were correlated to the humoural antimicrobial activity. Overall, this study indicates that abalone may have more resilience to viruses than bacterial pathogens under conditions of elevated temperature, such as those predicted under future climate change scenarios. PMID- 22306750 TI - Staff education: defining what is needed is more important than ever. PMID- 22306752 TI - Identifying and responding to child abuse in the home. AB - Given the sheer numbers of abused children, home health clinicians will likely encounter youngsters who are living in volatile and neglectful homes. This article details information that is designed to assist clinicians to identify and respond to child abuse and neglect. PMID- 22306753 TI - Perspectives from family caregivers receiving home nursing support: findings from a qualitative study of home care patients with heart failure. AB - Many heart failure (HF) patients depend on a family caregiver and many families need additional home care nursing support. This qualitative study identified perspectives of being a HF caregiver for families receiving home care nursing. Eleven caregivers of homebound HF patients were interviewed on what helps them the most, their own health, obstacles in caregiving, and greatest needs overall. Eight themes emerged and will be discussed in this article. The findings articulate the positive influence nurses can have on HF families to guide future practice and research. PMID- 22306754 TI - Improving community health nurses' knowledge of heart failure education principles: a descriptive study. AB - The number of individuals diagnosed with heart failure continues to increase, often requiring repeated hospitalizations and readmissions. Patient education is essential for patients to self-manage this chronic illness. This study aims to describe nurses' knowledge of heart failure self-management education principles. Sixty-one nurses working in the community completed a 20-item survey, assessing their knowledge of diet, fluids, weight changes, signs and symptoms of worsening condition, medications, and exercise. Correct responses for individual survey items ranged from 14% to 100% with only 2 of 20 questions answered correctly by all participants. Frequently missed questions focused on notification of the physician regarding blood pressure, dizziness, weight monitoring, and use of salt substitutes. Findings of this study appear to suggest that an education and communication intervention may be effective at improving nurses' knowledge of heart failure education principles because more questions were answered correctly by >90% of nurses, following the intervention. PMID- 22306756 TI - Decreasing accidental mortality of ventilator-dependent children at home: a call to action. AB - An estimated 8,000 children in the United States are dependent on mechanical ventilation at home. Despite technological advances for home monitoring of ventilated patients, the preventable death rate among these children has not changed significantly during the last 2 decades. Analysis of the data indicate that the primary causes of preventable death in ventilator-dependent children at home are inadequate training, improper response, and a lack of vigilance by the clinicians who care for them. PMID- 22306758 TI - The fundamentals of hospice compliance: what is it and what are the implications for the future? An overview for hospice clinicians, part 1. AB - This article, Part 1 of a 2-part series, provides an overview of the current Medicare compliance climate and its implications for hospice providers. Content focuses on the 7 elements of a comprehensive compliance framework as defined by the Health and Human Services Office of the Inspector General in its 1999 Compliance Guidance for Hospices. A brief case example is provided and serves to set the stage for Part 2, which will explore hospice-specific risk areas and specific risk-reduction strategies. PMID- 22306761 TI - A community healthcare program that delivers transformational change. PMID- 22306762 TI - Death in the age of technology: one memorable hospice visit. AB - There have been many moments in my 11 years in nursing that I have felt were worthy to share. Having worked in the neonatal intensive care unit, then in pediatrics, and now in palliative care and hospice, there have been a multitude of experiences that have warmed my being and affirmed my choice of profession. I wanted to communicate 1 of my most recent experiences that occurred with a hospice patient and his family on the day of his death. PMID- 22306763 TI - SIS along a continuum (SIS(c)) epidemiological modelling and control of diseases on directed trade networks. AB - Network theory has been applied to many aspects of biosciences, including epidemiology. Most epidemiological models in networks, however, have used the standard assumption of either susceptible or infected individuals. In some cases (e.g. the spread of Phytophthora ramorum in plant trade networks), a continuum in the infection status of nodes can better capture the reality of epidemics in networks. In this paper, a Susceptible-Infected-Susceptible model along a continuum in the infection status (SIS(c)) is presented, using as a case study directed networks and two parameters governing the epidemic process (probability of infection persistence (p(p)) and of infection transmission (p(t)). The previously empirically reported linear epidemic threshold in a plot of p(p) as a function of p(t) (Pautasso and Jeger, 2008) is derived analytically. Also the previously observed negative correlation between the epidemic threshold and the correlation between links in and out of nodes (Moslonka-Lefebvre et al., 2009) is justified analytically. A simple algorithm to calculate the threshold conditions is introduced. Additionally, a control strategy based on targeting market hierarchical categories such as producers, wholesalers and retailers is presented and applied to a realistic reconstruction of the UK horticultural trade network. Finally, various applications (e.g., seed exchange networks, food trade, spread of ideas) and potential refinements of the SIS(c) model are discussed. PMID- 22306764 TI - Kinetic model of HIV infection including hematopoietic progenitor cells. AB - Recent experiments indicate that one of the likely reasons of the failure of eradication of HIV is in infection of hematopoietic progenitor cells. Such cells are nurtured in stem-cell niches residing in the bone marrow. Our generic four variable kinetic model focused on this ingredient of HIV infection describes (i) a rapid increase of the population of infected CD4+ T cells at the beginning of verimia, (ii) a sharp decline of this population due to immunological control, (iii) a long period of latency followed by a collapse of the immune system, and (iv) predicts that in the case of the therapy fully eradicating infected CD4+ T cells the infection starts rapidly again after the therapy. PMID- 22306765 TI - Tyrosine triad at the interface between the Rieske iron-sulfur protein, cytochrome c1 and cytochrome c2 in the bc1 complex of Rhodobacter capsulatus. AB - A triad of tyrosine residues (Y152-154) in the cytochrome c(1) subunit (C1) of the Rhodobacter capsulatus cytochrome bc(1) complex (BC1) is ideally positioned to interact with cytochrome c(2) (C2). Mutational analysis of these three tyrosines showed that, of the three, Y154 is the most important, since its mutation to alanine resulted in significantly reduced levels, destabilization, and inactivation of BC1. A second-site revertant of this mutant that regained photosynthetic capacity was found to have acquired two further mutations-A181T and A200V. The Y152Q mutation did not change the spectral or electrochemical properties of C1, and showed wild-type enzymatic C2 reduction rates, indicating that this mutation did not introduce major structural changes in C1 nor affect overall activity. Mutations Y153Q and Y153A, on the other hand, clearly affect the redox properties of C1 (e.g. by lowering the midpoint potential as much as 117 mV in Y153Q) and the activity by 90% and 50%, respectively. A more conservative Y153F mutant on the other hand, behaves similarly to wild-type. This underscores the importance of an aromatic residue at position Y153, presumably to maintain close packing with P184, which modeling indicates is likely to stabilize the sixth heme ligand conformation. PMID- 22306766 TI - [Frequency of dermatophytes in a sample of cats in the urban area of Gran Mendoza, Argentina]. AB - BACKGROUND: The cat, considered the main reservoir of Microsporum canis, lives in urban areas, and also plays an important role in the emergence of dermatomycoses. AIMS: To determine and analyse the frequency of zoonotic dermatophytes in a sample of cats in an urban area of the Gran Mendoza region. METHODS: The animals selected were household cats and cats less than one year old that came from shelters and kennels from urban areas in the Gran Mendoza region. A total of 45 samples from cats with and without dermatological lesions were analysed. These samples were collected through skin scraping, hair removal and Mackenzie brush, respectively. Direct observation was made with KOH and glycerol after heat exposure. Samples were cultured on Sabouraud and Lactrimel agar slants with chloramphenicol and cycloheximide for 30 days. RESULTS: The frequency of dermatophytes isolated in this preliminary study was 13.3%. There were not statistically significant differences by source, age, sex, race or dermatological condition. Zoonotic dermatophytes were found in 2 household cats out of the 21 that had direct contact with children or the elderly. M. canis was isolated in 83.3% cases. CONCLUSIONS: The frequency of isolation of zoonotic dermatophytes in the sample of cats in an urban area of the Gran Mendoza region was 13.3%, a value higher than expected. M. canis was the most isolated species. PMID- 22306767 TI - Cardamonin from Alpinia rafflesiana inhibits inflammatory responses in IFN gamma/LPS-stimulated BV2 microglia via NF-kappaB signalling pathway. AB - The increasing prevalence of neurodegenerative diseases has prompted investigation into innovative therapeutics over the last two decades. Non steroidal anti-inflammatory drugs (NSAIDs) are among the therapeutic choices to control and suppress the symptoms of neurodegenerative diseases. However, NSAIDs associated gastropathy has hampered their long term usage despite their clinical advancement. On the natural end of the treatment spectrum, our group has shown that cardamonin (2',4'-dihydroxy-6'-methoxychalcone) isolated from Alpinia rafflesiana exerts potential anti-inflammatory activity in activated macrophages. Therefore, we further explored the anti-inflammatory property of cardamonin as well as its underlying mechanism of action in IFN-gamma/LPS-stimulated microglial cells. In this investigation, cardamonin shows promising anti-inflammatory activity in microglial cell line BV2 by inhibiting the secretion of pro inflammatory mediators including nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6). The inhibition of NO and PGE(2) by cardamonin are resulted from the reduced expression of inducible nitric oxide synthase (iNOS) and cycloxygenase-2 (COX-2), respectively. Meanwhile the suppressive effects of cardamonin on TNF-alpha, IL-1beta and IL-6 were demonstrated at both protein and mRNA levels, thus indicating the interference of upstream signal transduction pathway. Our results also validate that cardamonin interrupts nuclear factor kappa B (NF-kappaB) signalling pathway via attenuation of NF-kappaB DNA binding activity. Interestingly, cardamonin also showed a consistent suppressive effect on the cell surface expression of CD14. Taken together, our experimental data provide mechanistic insights for the anti-inflammatory actions of cardamonin in BV2 and thus suggest a possible therapeutic application of cardamonin for targeting neuroinflammatory disorders. PMID- 22306768 TI - Fluid biopsy in patients with metastatic prostate, pancreatic and breast cancers. AB - Hematologic spread of carcinoma results in incurable metastasis; yet, the basic characteristics and travel mechanisms of cancer cells in the bloodstream are unknown. We have established a fluid phase biopsy approach that identifies circulating tumor cells (CTCs) without using surface protein-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. This 'HD-CTC' assay finds >5 HD-CTCs mL(-1) of blood in 80% of patients with metastatic prostate cancer (n = 20), in 70% of patients with metastatic breast cancer (n = 30), in 50% of patients with metastatic pancreatic cancer (n = 18), and in 0% of normal controls (n = 15). Additionally, it finds HD-CTC clusters ranging from 2 HD-CTCs to greater than 30 HD-CTCs in the majority of these cancer patients. This initial validation of an enrichment-free assay demonstrates our ability to identify significant numbers of HD-CTCs in a majority of patients with prostate, breast and pancreatic cancers. PMID- 22306769 TI - Self-limited plasmonic welding of silver nanowire junctions. AB - Nanoscience provides many strategies to construct high-performance materials and devices, including solar cells, thermoelectrics, sensors, transistors, and transparent electrodes. Bottom-up fabrication facilitates large-scale chemical synthesis without the need for patterning and etching processes that waste material and create surface defects. However, assembly and contacting procedures still require further development. Here, we demonstrate a light-induced plasmonic nanowelding technique to assemble metallic nanowires into large interconnected networks. The small gaps that form naturally at nanowire junctions enable effective light concentration and heating at the point where the wires need to be joined together. The extreme sensitivity of the heating efficiency on the junction geometry causes the welding process to self-limit when a physical connection between the wires is made. The localized nature of the heating prevents damage to low-thermal-budget substrates such as plastics and polymer solar cells. This work opens new avenues to control light, heat and mass transport at the nanoscale. PMID- 22306770 TI - Ultrastable nanostructured polymer glasses. AB - Owing to the kinetic nature of the glass transition, the ability to significantly alter the properties of amorphous solids by the typical routes to the vitreous state is restricted. For instance, an order of magnitude change in the cooling rate merely modifies the value of the glass transition temperature (T(g)) by a few degrees. Here we show that matrix-assisted pulsed laser evaporation (MAPLE) can be used to form ultrastable and nanostructured glassy polymer films which, relative to the standard poly(methyl methacrylate) glass formed on cooling at standard rates, are 40% less dense, have a 40 K higher T(g), and exhibit a two orders of magnitude enhancement in kinetic stability at high temperatures. The unique set of properties of MAPLE-deposited glasses may make them attractive in technologies where weight and stability are central design issues. PMID- 22306771 TI - The shear mode of multilayer graphene. AB - The quest for materials capable of realizing the next generation of electronic and photonic devices continues to fuel research on the electronic, optical and vibrational properties of graphene. Few-layer graphene (FLG) flakes with less than ten layers each show a distinctive band structure. Thus, there is an increasing interest in the physics and applications of FLGs. Raman spectroscopy is one of the most useful and versatile tools to probe graphene samples. Here, we uncover the interlayer shear mode of FLGs, ranging from bilayer graphene (BLG) to bulk graphite, and suggest that the corresponding Raman peak measures the interlayer coupling. This peak scales from ~43 cm(-1) in bulk graphite to ~31 cm( 1) in BLG. Its low energy makes it sensitive to near-Dirac point quasiparticles. Similar shear modes are expected in all layered materials, providing a direct probe of interlayer interactions. PMID- 22306772 TI - [Synthetic calcium phosphate ceramics in secondary alveoloplasty]. AB - INTRODUCTION: Bone substitutes are rarely used in the reconstruction of cleft lip and palate. The graft material of choice is cancellous bone, harvested in the hip or tibia. Tibial harvesting may lead to postoperative morbidity, or even complications. This has lead surgeons to develop alternative solution. We present a secondary alveolar bone grafting technique using synthetic calcium phosphate ceramics. OBSERVATION: A patient presenting with a complete unilateral cleft lip and palate was treated by alveolar bone grafting at the age of nine years, using a mixture of autologous bone, harvested on the operative field, and particles of biphasic calcium phosphate (BCP); the graft was included in a platelet rich plasma (PRP) gel. The patient was followed up for eight years after the procedure. No sign of early or late infection was observed. At the end of facial growth, the cuspid had erupted correctly in a safe periodontal environment. Sequential X-rays showed complete filling of the initial bone defect, progressive resorption of ceramics, and spontaneous eruption of the cuspid. DISCUSSION: In this long-term follow-up report, the use of BCP mixed with autologous bone did not interfere with dental eruption or maxilla growth. A second bone-harvesting site was thus avoided. BCP could be a suitable alternative to autologous bone graft for secondary alveoloplasty. PMID- 22306773 TI - Glutamate oxidative injury to RGC-5 cells in culture is necrostatin sensitive and blunted by a hydrogen sulfide (H2S)-releasing derivative of aspirin (ACS14). AB - Oxidative stress to RGC-5 cells in culture was delivered by exposure to a combination of glutamate (Glu) and buthionine-S,R-sulfoximine (BSO). The effect of the insult on cell survival was quantified by the resazurin-reduction and a dead/live assays. Moreover, breakdown of DNA, the localisation of phosphatidylserine and reactive radical species (ROS) and its quantification were determined. In addition, various proteins and mRNAs were studied using Western blot, real time PCR and immunocytochemistry. ACS14, its sulfurated moiety ACS1 and aspirin were tested for their ability to blunt the negative effects of Glu/BSO on RGC-5 cells. In addition assays were carried out to see whether any of these substances influenced glutathione (GSH). Glu/BSO dose-dependently kills RGC 5 cells by a mechanism that involves an elevation of ROS accompanied by a breakdown of DNA, expression of phosphatidylserine and the activation of p38 MAPK. The process is unaffected by the pan caspase inhibitor z-VAD-fmk, does not involve the activation of apoptosis inducing factor (AIF) but is sensitive to active necrostatin-1. In cell viability studies (resazurin-reduction assay), ACS1 and ACS14 equally counteracted the negative effects of 5mM Glu/BSO to RGC-5 cells but aspirin was only effective with a milder oxidative stress (1 mM Glu/BSO). In all other assays ACS14 was very much more effective than aspirin at counteracting the influence of 5mM Glu/BSO. Moreover, ACS14 and ACS1 directly stimulated GSH while aspirin was ineffective. In addition the neuroprotecive effect of ACS14 was specifically blunted by the non-specific potassium channel blocker glibenclamide. Also the up-regulation of Bcl-2, HO-1 and XIAP induced by 5mM Glu/BSO were all attenuated to a greater extent by ACS14 (20 MUM) than aspirin (20 MUM). These data show that ACS14 is a very effective neuroprotectant when compared with aspirin. ACS14 maintains its aspirin characteristics and has the ability to release H(2)S. The combined multiple actions of aspirin and H(2)S in the form of ACS14 is worthy to consider for possible use in the treatment of glaucoma. PMID- 22306774 TI - Involvement of glucocorticoid-mediated Zn2+ signaling in attenuation of hippocampal CA1 LTP by acute stress. AB - Glucocorticoid-glutamatergic interactions have been proposed as a potential model to explain stress-mediated impairment of cognition. However, it is unknown whether glucocorticoid-zincergic interactions are involved in this impairment. Histochemically reactive zinc (Zn(2+)) is co-released with glutamate from zincergic neurons. In the present study, involvement of synaptic Zn(2+) in stress induced attenuation of CA1 LTP was examined in hippocampal slices from young rats after exposure to tail suspension stress for 30s, which significantly increased serum corticosterone. Stress-induced attenuation of CA1 LTP was ameliorated by administration of clioquinol, a membrane permeable zinc chelator, to rats prior to exposure to stress, implying that the reduction of synaptic Zn(2+) by clioquinol participates in this amelioration. To pursue the involvement of corticosterone-mediated Zn(2+) signal in the attenuated CA1 LTP by stress, dynamics of synaptic Zn(2+) was checked in hippocampal slices exposed to corticosterone. Corticosterone increased extracellular Zn(2+) levels measured with ZnAF-2 dose-dependently, as well as the intracellular Ca(2+) levels measured with calcium orange AM, suggesting that corticosterone excites zincergic neurons in the hippocampus and increases Zn(2+) release from the neuron terminals. Intracellular Zn(2+) levels measured with ZnAF-2DA were also increased dose dependently, but not in the coexistence of CaEDTA, a membrane-impermeable zinc chelator, suggesting that intracellular Zn(2+) levels is increased by the influx of extracellular Zn(2+). Furthermore, corticosterone-induced attenuation of CA1 LTP was abolished in the coexistence of CaEDTA. The present study suggests that corticosterone-mediated increase in postsynaptic Zn(2+) signal in the cytosolic compartment is involved in the attenuation of CA1 LTP after exposure to acute stress. PMID- 22306775 TI - Target-based drug discovery, genetic diseases, and biologics. AB - The last fifteen years have witnessed a major strategic shift in drug discovery away from an empiric approach based on incremental improvements of proven therapies, to a more theoretical, target-based approach. This arose as a consequence of three technical advances: (1) generation and interpretation of genome sequences, which facilitated identification and characterization of potential drug targets; (2) efficient production of candidate ligands for these putative targets through combinatorial chemistry or generation of monoclonal antibodies; and (3) high-throughput screening for rapid evaluation of interactions of these putative ligands with the selected targets. The basic idea underlying all three of these technologies is in keeping with Marshall Nirenberg's dictum that science progresses best when there are simple assays capable of generating large data sets rapidly. Furthermore, practical implementation of target-based drug discovery was enabled directly by technologies that either were originated or nurtured by Marshall, his post-docs and fellows. Chief among these was the genetic code. Also important was adoption of clonal cell lines for pharmacological investigations, as well as the use of hybridomas to generate molecular probes that allowed physical purchase on signaling elements that had previously been only hypothetical constructs. Always the pure scientist, Marshall's contributions nevertheless enabled fruitful applications in the pharmaceutical industry, several of them by his trainees. Both the successes and the shortcomings of target-based drug discovery are worthy of consideration, as are its implications for the choices of therapeutic goals and modalities by the pharmaceutical industry. PMID- 22306776 TI - The glutamate transporter, GLAST, participates in a macromolecular complex that supports glutamate metabolism. AB - GLAST is the predominant glutamate transporter in the cerebellum and contributes substantially to glutamate transport in forebrain. This astroglial glutamate transporter quickly binds and clears synaptically released glutamate and is principally responsible for ensuring that synaptic glutamate concentrations remain low. This process is associated with a significant energetic cost. Compartmentalization of GLAST with mitochondria and proteins involved in energy metabolism could provide energetic support for glutamate transport. Therefore, we performed immunoprecipitation and co-localization experiments to determine if GLAST might co-compartmentalize with proteins involved in energy metabolism. GLAST was immunoprecipitated from rat cerebellum and subunits of the Na(+)/K(+) ATPase, glycolytic enzymes, and mitochondrial proteins were detected. GLAST co localized with mitochondria in cerebellar tissue. GLAST also co-localized with mitochondria in fine processes of astrocytes in organotypic hippocampal slice cultures. From these data, we hypothesized that mitochondria participate in a macromolecular complex with GLAST to support oxidative metabolism of transported glutamate. To determine the functional metabolic role of this complex, we measured CO(2) production from radiolabeled glutamate in cultured astrocytes and compared it to overall glutamate uptake. Within 15 min, 9% of transported glutamate was converted to CO(2). This CO(2) production was blocked by inhibitors of glutamate transport and glutamate dehydrogenase, but not by an inhibitor of glutamine synthetase. Our data support a model in which GLAST exists in a macromolecular complex that allows transported glutamate to be metabolized in mitochondria to support energy production. PMID- 22306777 TI - Hypoxic stress activates chaperone-mediated autophagy and modulates neuronal cell survival. AB - Autophagy is a conserved mechanism responsible for the continuous clearance of unnecessary organelles or misfolded proteins in lysosomes. Three types of autophagy have been reported in the difference of substrate delivery to lysosome: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Among these types, CMA is a unique autophagy system that selectively degrades substrates detected by heat shock cognate protein 70 (HSC70). Recently, autophagic cell death has been reported to be involved in neuronal death following brain ischemia; however, the contribution of CMA to neuronal death/survival after ischemic stress has not been addressed. In the present study, we determined whether quantitative alterations in LAMP-2A, which is the key molecule in CMA, would modulate neuronal cell survival under hypoxic conditions. Incubation of Neuro2A cells in a hypoxic chamber (1% O(2), 5% CO(2)) increased the level of LAMP-2A and induced accumulation of LAMP-2A-positive lysosomes in the perinuclear area, which is a hallmark of CMA activation. The activation of CMA in response to hypoxia was also confirmed by the GAPDH-HaloTag CMA indicator system at the single cell level. Next, we asked whether CMA was involved in cell survival during hypoxia. Blocking LAMP-2A expression with siRNA increased the level of cleaved caspase-3 and the number of propidium iodide positive cells after hypoxic stress regardless of whether macroautophagy could occur, whereas the administration of mycophenolic acid, a potent CMA activator, rescued hypoxia-mediated cell death. Finally, we asked whether CMA was activated in the neurons after middle cerebral artery occlusion in vivo. The expression of LAMP-2A was significantly increased in the ischemic hemisphere seven days after brain ischemia. These results indicate that CMA is activated during hypoxia and contributes to the survival of cells under these conditions. PMID- 22306778 TI - Endogenous TDP-43 localized to stress granules can subsequently form protein aggregates. AB - TDP-43 proteinopathies are characterized by loss of nuclear TDP-43 and accumulation of the protein in the cytosol as ubiquitinated protein aggregates. These protein aggregates may have an important role in subsequent neuronal degeneration in motor neuron disease, frontotemporal dementia and potentially other neurodegenerative diseases. Although the cellular mechanisms driving the abnormal accumulation of TDP-43 are not understood, recent studies have shown that an early change to TDP-43 metabolism in disease may be accumulation in cytosolic RNA stress granules (SGs). However, it is unclear whether the TDP-43 in these SGs progresses to become irreversible protein aggregates as observed in patients. We have shown recently that paraquat-treated cells are a useful model for examining TDP-43 SG localization. In this study, we used the paraquat model to examine if endogenous TDP-43 in SGs can progress to more stable protein aggregates. We found that after treatment of HeLa cells overnight with paraquat, TDP-43 co-localized to SGs together with the ubiquitous SG marker, human antigen R (HuR). However, after a further incubation in paraquat-free, conditioned medium for 6h, HuR-positive SGs were rarely detected yet TDP-43 positive aggregates remained present. The majority of these TDP-43 aggregates were positive for ubiquitin. Further evidence for persistence of TDP-43 aggregates was obtained by treating cultures with cycloheximide after paraquat treatment. Cycloheximide abolished nearly all cytosolic HuR aggregation (SGs) but large TDP-43-positive aggregates remained. Finally, we showed that addition of ERK and JNK inhibitors together with paraquat blocked TDP-43-positive SG formation, while treatment with inhibitors after 24h paraquat exposure failed to reverse the TDP-43 accumulation. This failure was most likely due to the addition of inhibitors after maximal activation of the kinases at 4h post-paraquat treatment. These findings provide strong evidence that once endogenous TDP-43 accumulates in SGs, it has the potential to progress to stable protein aggregates as observed in neurons in TDP 43 proteinopathies. This may provide a therapeutic opportunity to inhibit the transition of TDP-43 from SG protein to aggregate. PMID- 22306779 TI - Transglutaminase regulates immune-related genes in shrimp. AB - Transglutaminase (TGase) is known to be involved in blood coagulation, a conserved defence mechanism among invertebrates. Gene silencing of TGase was previously shown to render shrimp susceptible to both bacterial and viral infections suggesting that TGase is an essential component of the shrimp immune system. Here, we examine the effects of the absence of TGase on the transcriptomic profile of kuruma shrimp by microarray analysis, focussing on genes that are involved in shrimp immunity. Total RNAs from shrimp haemocytes injected with dsRNA specific for TGase and control samples were isolated at 3 and 7 days p.i. and analyzed by microarray. Results revealed that TGase silencing affects the expression of genes in shrimp and caused significant down-regulation of the expressions of crustin and lysozyme. Furthermore, TGase-depleted samples were found to have lower haemocyte counts and higher total bacterial counts in their haemolymph. These results suggest that TGase is an important component of the shrimp immune response and is involved in the regulation of some immune related genes particularly antimicrobial peptides. PMID- 22306780 TI - Protease-activated receptor 1 (PAR1) coupling to G(q/11) but not to G(i/o) or G(12/13) is mediated by discrete amino acids within the receptor second intracellular loop. AB - Protease-activated receptor 1 (PAR1) is an unusual GPCR that interacts with multiple G protein subfamilies (G(q/11), G(i/o), and G(12/13)) and their linked signaling pathways to regulate a broad range of pathophysiological processes. However, the molecular mechanisms whereby PAR1 interacts with multiple G proteins are not well understood. Whether PAR1 interacts with various G proteins at the same, different, or overlapping binding sites is not known. Here we investigated the functional and specific binding interactions between PAR1 and representative members of the G(q/11), G(i/o), and G(12/13) subfamilies. We report that G(q/11) physically and functionally interacts with specific amino acids within the second intracellular (i2) loop of PAR1. We identified five amino acids within the PAR1 i2 loop that, when mutated individually, each markedly reduced PAR1 activation of linked inositol phosphate formation in transfected COS-7 cells (functional PAR1 null cells). Among these mutations, only R205A completely abolished direct G(q/11) binding to PAR1 and also PAR1-directed inositol phosphate and calcium mobilization in COS-7 cells and PAR1-/- primary astrocytes. In stark contrast, none of the PAR1 i2 loop mutations disrupted direct PAR1 binding to either G(o) or G(12), or their functional coupling to linked pertussis toxin-sensitive ERK phosphorylation and C3 toxin-sensitive Rho activation, respectively. In astrocytes, our findings suggest that PAR1-directed calcium signaling involves a newly appreciated G(q/11)-PLCepsilon pathway. In summary, we have identified key molecular determinants for PAR1 interactions with G(q/11), and our findings support a model where G(q/11), G(i/o) or G(12/13) each bind to distinct sites within the cytoplasmic regions of PAR1. PMID- 22306781 TI - Left main compression by an aortic root abscess. AB - A 79-year-old man with severe aortic stenosis, history of coronary artery disease and a recent hospitalization for sepsis presented at our institution following a syncope and angina at rest. Coronary angiography and aortography showed an aortic root abscess, causing left main coronary artery compression. This life threatening complication of aortic valve endocarditis is rare and requires immediate surgical correction. PMID- 22306782 TI - The effect of valsartan on left ventricular myocardial functions in hypertensive patients with left ventricular hypertrophy. AB - BACKGROUND: It has been shown by various diagnostic methodologies that angiotensin receptor blockage reduces left ventricular mass, improves diastolic function and increases contractility in hypertensive left ventricular hypertrophy (LVH). We planned to detect the effect of angiotensin receptor blockage on midwall mechanics and myocardial dynamics in hypertensive patients with LVH. METHODS: Angiotensin 2 type 1 receptor blocker (valsartan 80-160 mg) was administered to 38 previously untreated hypertensive patients with LVH for 6 months. Left ventricular midwall mechanics and tissue Doppler velocities were measured at baseline and at the end of the study. RESULTS: Mean blood pressure was reduced from 152 +/- 14/92 +/- 8 to 131 +/- 14/83 +/- 9 mmHg (P < 0.05). Left ventricular mass index was decreased from 135 +/- 15 to 114 +/- 14 g/m(2) (P < 0.001). Midwall fractional shortening was increased from 19.0 +/- 4 to 22.4 +/- 3% (P < 0.05). Circumferential end-systolic wall stress was decreased from 131 +/ 44 to 119 +/- 37 * 10(3) dyn/cm(2) (P < 0.05). Left ventricular interventricular septal myocardial tissue peak systolic velocity was increased from 6.7 +/- 1 to 8.1 +/- 0.9 cm/s (P < 0.001) and lateral wall myocardial tissue peak systolic velocity was increased from 7.5 +/- 1 to 9.0 +/- 1 cm/s (P < 0.001), and E/E(m) ratio was significantly decreased (11.0 +/- 0.3 to 8.90 +/- 0.1, P < 0.05) with 6 month valsartan therapy. CONCLUSION: This study suggests that valsartan exhibits not only blood pressure-lowering qualities but also cardioprotective actions in patients with hypertension because it enhances regression of LVH and improves left ventricular myocardial contractility and relaxation. PMID- 22306783 TI - An unusual cause of cardiac failure. AB - Left ventricular noncompaction (LVNC) is a rare cardiomyopathy characterized by deep intertrabecular recesses communicating with the main ventricular chamber. Cardiac magnetic resonance offers high spatial resolution, and thereby substantial aptitude for the diagnosis of LVNC. Additional clinically relevant information, including thrombus and myocardial fibrosis evaluation, can be readily acquired. These images demonstrate classical LVNC morphology in conjunction with its potential sequelae. PMID- 22306784 TI - Different properties of complex fractionated atrial electrograms during atrial fibrillation. AB - AIMS: The aim of the present study was to investigate various properties of complex fractionated atrial electrograms (CFAEs) in different models of atrial fibrillation. METHODS: Fifteen dogs were divided into three groups (five dogs/group): group 1 (pacing-induced atrial fibrillation group), group 2 (100 mM Ach-induced atrial fibrillation group), group 3 (500 mM Ach-induced atrial fibrillation group). Five sites from the left atrium in each dog were used as recording sites. Electric stimulations were used to induce atrial fibrillation. Effective refractory period (ERP) of each recording site and atrial fibrillation inducibility index were obtained at baseline and following sustained atrial tachypacing for 4 h (group 1) or acetylcholine (Ach) application (groups 2 and 3). During the first induced atrial fibrillation, recording sites with CFAEs were identified and domain frequency of CFAE was obtained. RESULTS: ERPs decreased significantly compared to baseline in all groups (P < 0.001). There was no significant difference in decrements of ERPs at each site after pacing in group 1 (P = 0.646); in groups 2 and 3, significant differences were found in decrements of ERPs following Ach application when each site was compared (P < 0.05). Atrial fibrillation inducibility index increased in all groups compared to baseline (P < 0.05). During the first induced atrial fibrillation, CFAEs were recorded at all sites. There was no significant difference of domain frequencies in group 1 when each site was compared (P = 0.509), but significant differences in domain frequencies were found in groups 2 and 3 when each site was compared (P < 0.05). CONCLUSION: We identified that various characteristics of CFAEs may exist in different experimental models of atrial fibrillation. This may indicate different mechanisms of CFAEs. PMID- 22306785 TI - Value of cardiovascular magnetic resonance in suspected cardiac amyloidosis. AB - The diagnosis of cardiac amyloid can be challenging; requiring a high clinical index of suspicion and often many diagnostic tests to confirm. We describe a case demonstrating the characteristic pattern of amyloid by cardiovascular magnetic resonance and how this imaging modality can aid in the diagnosis. PMID- 22306787 TI - Two late complications of craniofacial trauma: case report and review of the literature. AB - Injuries after blunt and penetrating trauma to the face are a common occurrence and are managed by specialists from several disciplines. After short-term care and immediate recovery, long-term complications can develop including cosmetic deformity, unsightly scarring, problems with soft tissue healing, malunion or nonunion of bony segments, diplopia or other visual complaints, malocclusion, hardware failure, and mucocele formation. Here, we present a report of 2 late complications recognized and treated in a patient 40 years after an episode of craniofacial trauma: epistaxis with symptomatic nasal congestion from fixation wires and mucocele formation. Management of this patient accompanied by endoscopic photographs and computed tomographic images is presented, and discussion of these complications along with review of the literature is provided. PMID- 22306788 TI - Radix astragali injection enhances recovery from sudden deafness. AB - OBJECTIVES: An acute interruption of the blood supply to the inner ear is one of the most likely causative factors for sudden deafness (SD). Reactive oxygen species (ROS) have been suggested to be important mediators of the tissue injury during cochlear ischemia and reperfusion. Radix astragali (RA) is natural antioxidant. The aim of this study was to investigate the efficacy of RA in patients with SD. PATIENTS AND METHODS: We compared the hearing gains from hearing impairment in 46 ears treated with RA with 46 ears treated with non-RA. RA was given intravenously daily for 10 days. There were no significant differences in clinical or audiological data between RA and non-RA groups. RESULTS: The hearing gain at 250, 500, 1000, 2000, and 4000 Hz in RA group was much higher than that of non-RA group correspondingly (P < .01). Also, the hearing gain at PTA (pure-tone average of 250, 500, 1000, 2000, and 4000 Hz) in RA group was significantly higher than that of non-RA group (P < .01). CONCLUSION: The recovery of hearing was significantly better after treatment of RA than non-treatment of RA. RA can be valuable concurrent therapy for patients with SD. PMID- 22306789 TI - Improving psychological treatment for obesity. Which eating behaviours should we target? AB - People who are obese and want to lose weight without surgery deserve the best treatment that we can offer. In the absence of robust and enduring treatment effects for psychological interventions for obesity, it is useful to return to first principles. From a behavioural perspective, the first task is to identify the full range of target eating behaviours involved in obesity. Surprisingly, a consensus on the key target eating behaviours typically involved in obesity does not seem to currently exist. In this opinion piece, we discuss which eating behaviours might be important to consider when treating obesity, and provide a self-report questionnaire that aims to identify these behaviours (see Supplementary material). We believe that it is important to be aware of the full range of eating behaviours that are potentially relevant to obesity, as different eating behaviours may be problematic for different people. Target eating behaviours associated with obesity may also be different from those of key relevance to eating disorders. Factors that should be taken into account when assessing target eating behaviours and developing effective treatments for obesity are also discussed. Particular attention is paid to 'grazing,' a relatively neglected high risk eating behaviour for weight gain. PMID- 22306791 TI - Interactions of the antifungal mycosubtilin with ergosterol-containing interfacial monolayers. AB - Mycosubtilin, an antimicrobial lipopeptide produced by Bacillus subtilis, is characterized by strong antifungal activities. The molecular mechanisms of its biological activities on the membranes of the sensitive yeasts or fungi have not yet been clearly elucidated. Our purpose was to mimic the mycosubtilin interactions with these membranes using various Langmuir monolayers. Since the major sterol of yeasts or fungi is ergosterol, the interactions of mycosubtilin with monolayers constituted by ergosterol, DPPC/ergosterol or DPPC/sphingomyelin/ergosterol were examined at different initial surface pressures (Pii). Plotting the mycosubtilin-induced surface pressure increases versus Pii allowed to determine that the exclusion pressures of mycosubtilin from these different monolayers is higher than the surface prevailing within the biological membranes. However, this behavior was lost when mycosubtilin was interacting with ergosteryl acetate-containing monolayers. This suggests the involvement of the sterol alcohol group in the mycosubtilin interactions within membranes. Furthermore, the behavior of mycosubtilin with stigmasterol, similar to that observed with ergosterol, differs from that previously observed with cholesterol, suggesting a role of the alkyl side chain of the sterols. The adsorption of mycosubtilin to ergosterol monolayers induced changes in the lipopeptide orientation at the air-water interface as revealed by polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS). Moreover, imaging the air-water interface by Brewster angle microscopy (BAM) indicates that mycosubtilin induced changes in the organization and morphology of monolayers containing pure ergosterol with the appearance of small condensed dots, suggesting again that the target of mycosubtilin might be the ergosterol present in the membranes of the sensitive yeasts or fungi. PMID- 22306790 TI - Regulation of senescence by microRNA biogenesis factors. AB - Senescence represents a state of indefinite growth arrest in cells that have reached the end of their replicative life span, have become damaged, or express aberrant levels of cancer-related proteins. While senescence is widely considered to represent a tumor-suppressive mechanism, the accumulation of senescent cells in tissues of older organisms is believed to underlie age-associated losses in physiologic function and age-related diseases. With the emergence of microRNAs (miRNAs) as a major class of molecular regulators of senescence, we review the transcriptional and post-transcriptional factors that control senescence associated microRNA biosynthesis. Focusing on their enhancement or repression of senescence, we describe the transcription factors that govern the synthesis of primary (pri-)miRNAs, the proteins that control the nuclear processing of pri miRNAs into precursor (pre-)miRNAs, including RNA editing enzymes, RNases, and RNA helicases, and the cytoplasmic proteins that affect the final processing of pre-miRNAs into mature miRNAs. We discuss how miRNA biogenesis proteins promote or inhibit senescence, and thus influence the senescent phenotype that affects normal tissue function and pathology. PMID- 22306792 TI - Comparison of acetylcholine receptor interactions of the marine toxins, 13 desmethylspirolide C and gymnodimine. AB - The interaction of 13-desmethylspirolide C (SPX-desMe-C) and gymnodimine with several nicotinic and muscarinic acetylcholine receptors was investigated. Interaction at the muscarinic receptors was minimal. At nicotinic receptors, both SPX-desMe-C and gymnodimine displayed greatest affinity for the alpha7 receptor. The rank order for binding affinity (Ki) for SPX-desMe-C was alpha7 > alpha6beta3beta4alpha5 >> rat alpha3beta4, alpha1betagammadelta > alpha4beta4, human alpha3beta4 > human alpha4beta2 > rat alpha4beta2 and for gymnodimine was alpha7, alpha6beta3beta4alpha5 > rat alpha3beta4 > human alpha3beta4, alpha4beta4 > rat alpha4beta2, human alpha4beta2 > alpha1betagammadelta. Both molecules antagonized agonist-induced nicotinic responses. The antagonism rank order of potency (IC(50)) for SPX-desMe-C was alpha7 > low sensitivity (LS) alpha4beta2 > human alpha3beta4 > high sensitivity (HS) alpha4beta2, alpha1betagammadelta > alpha4beta4 > rat alpha3beta4 and for gymnodimine was LS alpha4beta2 > human alpha3beta4 > alpha7 > HS alpha4beta2 > alpha4beta4 > rat alpha3beta4 > alpha1betagammadelta. Neither gymnodimine nor SPX-desMe-C antagonism could be surmounted by increasing concentrations of nicotine. To elucidate the nature of this insurmountable blockade, we carried out homology modelling and molecular docking studies of both ligands with alpha7 nAChR. Their very high binding affinity results from very tight hydrophobic enclosures, in addition to previously reported hydrogen-bond and cation-pi interactions. Also, the higher the hydrophilic surface area of the binding site of nAChRs, the weaker the binding affinity of both ligands. Together these results show the targets of action are nicotinic and define these marine toxins as additional tools to advance our understanding regarding interactions between antagonists and the nAChR ligand binding domain. PMID- 22306793 TI - Intrathecal alpha-conotoxins Vc1.1, AuIB and MII acting on distinct nicotinic receptor subtypes reverse signs of neuropathic pain. AB - The large diversity of peptides from venomous creatures with high affinity for molecules involved in the development and maintenance of neuropathic pain has led to a surge in venom-derived analgesic research. Some members of the alpha conotoxin family from Conus snails which specifically target subtypes of nicotinic acetylcholine receptors (nAChR) have been shown to be effective at reducing mechanical allodynia in neuropathic pain models. We sought to determine if three such peptides, Vc1.1, AuIB and MII were effective following intrathecal administration in a rat neuropathic pain model because they exhibit different affinities for the major putative pain relieving targets of alpha-conotoxins. Intrathecal administration of alpha-conotoxins, Vc1.1, AuIB and MII into neuropathic rats reduced mechanical allodynia for up to 6 h without significant side effects. In vitro patch-clamp electrophysiology of primary afferent synaptic transmission revealed the mode of action of these toxins was not via a GABA(B) dependent mechanism, and is more likely related to their action at nAChRs containing combinations of alpha3, alpha7 or other subunits. Intrathecal nAChR subunit-selective conotoxins are therefore promising tools for the effective treatment of neuropathic pain. PMID- 22306786 TI - Elderly patients with acute coronary syndromes admitted to Italian intensive cardiac care units: a Blitz-3 Registry sub-analysis. AB - BACKGROUND: Guideline-recommended therapies for acute coronary syndromes (ACS) derive from randomized trials in which elderly patients are underrepresented. Although numbers of this population are increasing, they are largely undertreated in the real world. OBJECTIVE: The study evaluates the impact of older age on care for patients with ACS admitted to the Italian Intensive Cardiac Care Units (ICCUs) network. METHODS: We analyzed data from the BLITZ-3 Registry in order to assess in-hospital care among unselected elderly patients (>=75 years). RESULTS: From 7-20 April 2008, 6986 consecutive patients with acute cardiac conditions were admitted to ICCUs and prospectively enrolled; 3636 (52%) had ACS and 38% of them were elderly. Elderly patients had a higher risk profile, their median length of stay in ICCU was longer [4 days, interquartile range (IQR): 3-6 vs. 3 days, IQR: 2-5; P < 0.0001] and guideline-recommended care was applied less often. At multivariable analysis, elderly patients were less likely to receive reperfusion [odds ratio (OR) = 0.53, 95% confidence interval (CI) = 0.42-0.67] for ST-elevation, or early coronary angiography (OR = 0.45, 95% CI = 0.37-0.56) for non-ST elevation ACS. Besides, unadjusted in-ICCU total mortality was higher for elderly patients with ST-elevation (11.8% elderly vs. 1.8% younger patients; P < 0.0001) or non-ST-elevation (3.9% elderly vs. 0.6% younger patients; P < 0.0001) ACS. CONCLUSION: In a nationwide survey, age impacts on care. The elderly with ACS have a higher risk profile but receive less guideline-recommended care than younger patients. Thus, further improvements in care of this population should be pursued. PMID- 22306795 TI - Carriage of Streptoccoccus pneumoniae 7 years after implementation of vaccination program in a population with very high and long-lasting coverage, Italy. AB - To evaluate how the 7-valent pneumococcal vaccine (PCV7) programme and the very high vaccination coverage reached for over 4 years affected the prevalence of Streptoccoccus pneumoniae serotypes in the paediatric population and to evaluate demographic, behavioural and risk factors for carriage in the post-vaccination era, a cross-sectional study on nasopharyngeal carriage was performed. Six hundred sixty-nine children under the age of 5, representative of the open population, were enrolled by cluster sampling. High sensitive techniques for detection of multi-serotype carriage, i.e. broth enrichment and real-time PCR and sequential PCRs for detection and typing, respectively, were used. Of the 669 enrolled children, 97.8% were compliant with the recommended PCV7 vaccination schedule. Post-stratification adjustment for age was applied considering the Ligurian population as standard population. Age-weighted carriage rate was 50.1% and 78% of carriers were colonized by more than one serotype. The prevalence of carriage increased with age from 22% in the first year of life, to 48.6% in the second year of life and to 60% in the 25-59 month age group. Age-weighted prevalence of any of the PCV7, PCV10 or PCV13 serotypes was 10.3%, 20.3% and 27.5%, respectively. PCV7 serotypes were mainly represented by serotype 4 that was carried since the 3rd year of life and was responsible for invasive pneumococcal disease (IPD) and non-IPD in adults, but not in children confirming the high vaccine effectiveness. Among the serotypes included in recently available vaccines, serotypes 5 and 19A showed a higher prevalence, being carried by 15.2% and 8.8% of the population, respectively. A multivariate analysis showed that age, the presence of child siblings at home and day care attendance covariates were strongly associated with S. pneumoniae carriage. In conclusion, over 7 years of vaccination with PCV7 and very high coverage in the last 4 years has led to low carriage prevalence in the first year of life rapidly increasing in the following years and high prevalence of non-PCV7 serotypes carriage. PMID- 22306794 TI - Referring physicians' discordance with the primary prevention implantable cardioverter-defibrillator guidelines: a national survey. AB - BACKGROUND: The American College of Cardiology, the American Heart Association, and the Heart Rhythm Society guidelines provide patient selection criteria for primary prevention implantable cardioverter-defibrillators (ICDs). For unknown reasons, guideline-discordant practice is common. OBJECTIVE: To determine referring physicians' concordance with the primary prevention ICD guidelines. METHODS: We mailed a survey regarding ICD guidelines and individual practice characteristics to a random national sample of 3000 physicians selected from the American Medical Association Masterfile-one-third each specializing in family medicine, internal medicine, and general cardiology. RESULTS: Sixty-four percent with correct contact information responded. Three hundred ninety-five (28%; 95% confidence interval [CI] 25%-30%) respondents never refer patients with the intent of consideration for a primary prevention ICD, including 7% (95% CI 5% 10%) of cardiologists. Two hundred twelve (15%; 95% CI 13%-17%) believe ventricular arrhythmias are required before a primary prevention ICD is indicated; 525 (36%; 95% CI 34%-39%) believe that an ejection fraction of >40% warrants a primary prevention ICD; and 361 (25%; 95% CI 23%-27%) would refer a patient for a primary prevention ICD within 40 days of a myocardial infarction. In multivariate analyses, family practice physicians and physicians residing in the western United States most often provided guideline-discordant answers, while cardiologists and those who refer to an electrophysiologist most often provided guideline-concordant answers. Primary care physicians who manage heart failure patients without referral to a subspecialist were not more likely to provide guideline-concordant answers. CONCLUSIONS: Answers discordant with the primary prevention ICD guidelines were common, suggesting that referring physician beliefs are an important barrier to appropriate patient referrals for primary prevention ICD implantation. PMID- 22306796 TI - Chimeric calicivirus-like particles elicit specific immune responses in pigs. AB - Virus-like particles (VLPs) have received considerable attention due to their potential application in veterinary vaccines and, in particular, VLPs from rabbit haemorrhagic disease virus (RHDV) have successfully shown to be good platforms for inducing immune responses against an inserted foreign epitope in mice. The aim of this study was to assess the immunogenicity of chimeric RHDV-VLPs as vaccine vectors in pigs. For this purpose, we have generated chimeric VLPs containing a well-known T epitope of 3A protein of foot-and-mouth disease virus (FMDV). Firstly, RHDV-VLPs were able to activate immature porcine bone marrow derived dendritic cells (poBMDCs) in vitro. Secondly, pigs were inoculated twice in a two-week interval with chimeric RHDV-VLPs at different doses intranasally or intramuscularly. One intramuscularly treated group was also inoculated with adjuvant MontanideTM ISA 206 at the same time. Specific IgG and IgA antibodies against RHDV-VLPs were induced and such levels were higher in the adjuvanted group compared with other groups. Interestingly, anti-RHDV-VLP IgA responses were higher in groups inoculated intramuscularly than those that received the VLPs intranasally. Two weeks after the last immunisation, specific IFN-gamma-secreting cells against 3A epitope and against RHDV-VLPs were detected in PBMCs by ELISPOT. The adjuvanted group exhibited the highest IFN-gamma-secreting cell numbers and lymphoproliferative specific T cell responses against 3A epitope and RHDV-VLP. This is the first immunological report on the potential use of chimeric RHDV-VLPs as antigen carriers in pigs. PMID- 22306797 TI - Detection of epileptic activity in fMRI without recording the EEG. AB - EEG-fMRI localizes epileptic foci by detecting cerebral hemodynamic changes that are correlated to epileptic events visible in EEG. However, scalp EEG is insensitive to activity restricted to deep structures and recording the EEG in the scanner is complex and results in major artifacts that are difficult to remove. This study presents a new framework for identifying the BOLD manifestations of epileptic discharges without having to record the EEG. The first stage is based on the detection of epileptic events for each voxel by sparse representation in the wavelet domain. The second stage is to gather voxels according to proximity in time and space of detected activities. This technique was evaluated on data generated by superposing artificial responses at different locations and responses amplitude in the brain for 6 control subject runs. The method was able to detect effectively and consistently for responses amplitude of at least 1% above baseline. 46 runs from 15 patients with focal epilepsy were investigated. The results demonstrate that the method detected at least one concordant event in 37/41 runs. The maps of activation obtained from our method were more similar to those obtained by EEG-fMRI than to those obtained by the other method used in this context, 2D-Temporal Cluster Analysis. For 5 runs without event read on scalp EEG, 3 runs showed an activation concordant with the patient's diagnostic. It may therefore be possible, at least when spikes are infrequent, to detect their BOLD manifestations without having to record the EEG. PMID- 22306798 TI - Temporal scaling characteristics of diffusion as a new MRI contrast: findings in rat hippocampus. AB - Features of the diffusion-time dependence of the diffusion-weighted magnetic resonance imaging (MRI) signal provide a new contrast that could be altered by numerous biological processes and pathologies in tissue at microscopic length scales. An anomalous diffusion model, based on the theory of Brownian motion in fractal and disordered media, is used to characterize the temporal scaling (TS) characteristics of diffusion-related quantities, such as moments of the displacement and zero-displacement probabilities, in excised rat hippocampus specimens. To reduce the effect of noise in magnitude-valued MRI data, a novel numerical procedure was employed to yield accurate estimation of these quantities even when the signal falls below the noise floor. The power-law dependencies characterize the TS behavior in all regions of the rat hippocampus, providing unique information about its microscopic architecture. The relationship between the TS characteristics and diffusion anisotropy is investigated by examining the anisotropy of TS, and conversely, the TS of anisotropy. The findings suggest the robustness of the technique as well as the reproducibility of estimates. TS characteristics of the diffusion-weighted signals could be used as a new and useful marker of tissue microstructure. PMID- 22306799 TI - Embodied empathy for tactile events: Interindividual differences and vicarious somatosensory responses during touch observation. AB - A growing body of evidence suggests an involvement of the somatosensory cortices for social perception. For example, it has been shown that observing touch on other bodies (in the absence of any real touch on the own body) affects somatosensory brain areas. Thus, understanding others' sensory experiences seems to rely on vicarious activation of somatosensory cortices. Recent studies also demonstrated that observation of painful and nonpainful touch engages the observer's somatosensory cortex differentially. The somatosensory activation during observation of painful stimulation has been related to trait differences in empathy, thereby drawing the attention to inter-individual differences in vicarious somatosensory activation. The current study aims to test the hypothesis if vicarious somatosensory activation during observation of nonpainful touch is also linked to inter-individual differences in empathy. We employed a functional magnetic resonance imaging (fMRI) paradigm to present video clips showing simple non-painful touch with a paintbrush to a hand relative to a control condition including the same visual and motion parts. Results revealed vicarious somatosensory activation when seeing the hand being touched. This activation was associated with trait differences in interpersonal reactivity. Thus, we found that the somatosensory response in primary somatosensory cortex (SI) was associated with the empathy subscale perspective taking. This link demonstrates that vicarious somatosensory responses for simple touch are influenced by the observer's personality traits, therefore suggesting a role for personality traits in a putative mirror neuron system. PMID- 22306800 TI - Normative database of judgment of complexity task with functional near infrared spectroscopy--application for TBI. AB - The ability to assess frontal lobe function in a rapid, objective, and standardized way, without the need for expertise in cognitive test administration might be particularly helpful in mild traumatic brain injury (TBI), where objective measures are needed. Functional near infrared spectroscopy (fNIRS) is a reliable technique to noninvasively measure local hemodynamic changes in brain areas near the head surface. In this paper, we are combining fNIRS and frameless stereotaxy which allowed us to co-register the functional images with previously acquired anatomical MRI volumes. In our experiment, the subjects were asked to perform a task, evaluating the complexity of daily life activities, previously shown with fMRI to activate areas of the anterior frontal cortex. We reconstructed averaged oxyhemoglobin and deoxyhemoglobin data from 20 healthy subjects in a spherical coordinate. The spherical coordinate is a natural representation of surface brain activation projection. Our results show surface activation projected from the medial frontopolar cortex which is consistent with previous fMRI results. With this original technique, we will construct a normative database for a simple cognitive test which can be useful in evaluating cognitive disability such as mild traumatic brain injury. PMID- 22306801 TI - Measuring longitudinal change in the hippocampal formation from in vivo high resolution T2-weighted MRI. AB - The hippocampal formation (HF) is a brain structure of great interest because of its central role in learning and memory, and its associated vulnerability to several neurological disorders. In vivo oblique coronal T2-weighted MRI with high in-plane resolution (~0.5 mm * 0.5 mm), thick slices (~2.0 mm), and a field of view tailored to imaging the hippocampal formation (denoted HF-MRI in this paper) has been advanced as a useful imaging modality for detailed hippocampal morphometry. Cross-sectional analysis of volume measurements derived from HF-MRI has shown the modality's promise to yield sensitive imaging-based biomarker for neurological disorders such as Alzheimer's disease. However, the utility of this modality for making measurements of longitudinal change has not yet been demonstrated. In this paper, using an unbiased deformation-based morphometry (DBM) pipeline, we examine the suitability of HF-MRI for estimating longitudinal change by comparing atrophy rates measured in the whole hippocampus from this modality with those measured from more common isotropic (~1 mm3) T1-weighted MRI in the same set of individuals, in a cohort of healthy controls and patients with cognitive impairment. While measurements obtained from HF-MRI were largely consistent with those obtained from T1-MRI, HF-MRI yielded slightly larger group effect of greater atrophy rates in patients than in controls. The estimated minimum sample size required for detecting a 25% change in patients' atrophy rate in the hippocampus compared to the control group with a statistical power beta=0.8 was N=269. For T1-MRI, the equivalent sample size was N=325. Using a dataset of test-retest scans, we show that the measurements were free of additive bias. We also demonstrate that these results were not a confound of certain methodological choices made in the DBM pipeline to address the challenges of making longitudinal measurements from HF-MRI, using a region of interest (ROI) around the HF to globally align serial images, followed by slice-by-slice deformable registration to measure local volume change. Additionally, we present a preliminary study of atrophy rate measurements within hippocampal subfields using HF-MRI. Cross-sectional differences in atrophy rates were detected in several subfields. PMID- 22306802 TI - The coupling controversy. AB - Functional magnetic resonance imaging (fMRI) relies on the well-known phenomenon of coupling between neuronal activity and brain blood flow. For nearly a century, the presumption was that hemodynamics were coupled to neuronal activity via energy demand and oxidative metabolism. Early (15)O positron-emission tomographic (PET) studies challenged this theory, demonstrating a physiological "uncoupling" between brain blood flow and oxygen metabolism. These PET observations played a pivotal role in guiding the development of fMRI, by demonstrating which physiological parameters were most closely coupled to neuronal activity and by presaging the BOLD-contrast effect. Subsequent PET studies were crucial for constraining theories concerning the physiological mechanisms underlying hemodynamic/neuronal coupling and, thereby, guiding the development of models for quantification of oxygen metabolic rate %? from fMRI. A first-person account of the PET "coupling" studies and their influence on the development of fMRI is provided. PMID- 22306803 TI - Interaction of COMT val158met and externalizing behavior: relation to prefrontal brain activity and behavioral performance. AB - A promising approach in neuroimaging studies aimed at understanding effects of single genetic variants on behavior is the study of gene-trait interactions. Variation in the catechol-O-methyl-transferase gene (COMT) is associated with the regulation of dopamine levels in the prefrontal cortex and with cognitive functioning. Given the involvement of dopaminergic neurotransmission in externalizing behavior, a trait characterized by impulsivity and aggression, especially in men, externalizing (as a trait) may index a set of genetic, environmental, and neural characteristics pertinent to understanding phenotypic effects of genetic variation in the COMT gene. In the current study, we used a gene-trait approach to investigate effects of the COMT val(158)met polymorphism and externalizing on brain activity during moments involving low or high demands on cognitive control. In 104 male participants, interference-related activation depended conjointly on externalizing and val(158)met: stronger activation in the dorsal anterior cingulate and lateral prefrontal cortex was found for val/val individuals with high trait externalizing while stronger activation in cingulate motor areas and sensorimotor precuneus was found for met/met individuals with low externalizing. Our results suggest that the val/val genotype, coupled with high levels of trait externalizing, lowers the efficiency of stimulus conflict resolution, whereas the met/met genotype, coupled with low levels of externalizing, lowers the efficiency of response selection. PMID- 22306804 TI - Can target-to-pons ratio be used as a reliable method for the analysis of [11C]PIB brain scans? AB - RATIONALE: (11)C]PIB is the most widely used PET imaging marker for amyloid in dementia studies. In the majority of studies the cerebellum has been used as a reference region. However, cerebellar amyloid may be present in genetic Alzheimer's (AD), cerebral amyloid angiopathy and prion diseases. Therefore, we investigated whether the pons could be used as an alternative reference region for the analysis of [(11)C]PIB binding in AD. The aims of the study were to: 1) Evaluate the pons as a reference region using arterial plasma input function and Logan graphical analysis of binding. 2) Assess the power of target-to-pons ratios to discriminate controls from AD subjects. 3) Determine the test-retest reliability in AD subjects. 4) Demonstrate the application of target-to-pons ratio in subjects with elevated cerebellar [(11)C]PIB binding. METHODS: 12 sporadic AD subjects aged 65 +/- 4.5 yrs with a mean MMSE 21.4 +/- 4 and 10 age matched control subjects had [(11)C]PIB PET with arterial blood sampling. Three additional subjects (two subjects with pre-symptomatic presenilin-1 mutation carriers and one probable familial AD) were also studied. Object maps were created by segmenting individual MRIs and spatially transforming the gray matter images into standard stereotaxic MNI space and then superimposing a probabilistic atlas. Cortical [(11)C]PIB binding was assessed with an ROI (region of interest) analysis. Parametric maps of the volume of distribution (V(T)) were generated with Logan analysis. Additionally, parametric maps of the 60-90 min target-to cerebellar ratio (RATIO(CER)) and the 60-90 min target-to-pons ratio (RATIO(PONS)) were computed. RESULTS: All three approaches were able to differentiate AD from controls (p<0.0001, nonparametric Wilcoxon rank sum test) in the target regions with RATIO(CER) and RATIO(PONS) differences higher than V(T) with use of an arterial input function. All methods had a good reproducibility (intraclass correlation coefficient>0.83); RATIO(CER) performed best closely followed by RATIO(PONS). The two subjects with presenilin-1 mutations and the probable familial AD case showed no significant differences in cortical binding using RATIO(CER), but the RATIO(PONS) approach revealed higher [(11)C]PIB binding in cortex and cerebellum. CONCLUSION: This study established 60-90 min target-to-pons RATIOs as a reliable method of analysis in [(11)C]PIB PET studies where cerebellum is not an appropriate reference region. PMID- 22306805 TI - Brain 'talks over' boring quotes: top-down activation of voice-selective areas while listening to monotonous direct speech quotations. AB - In human communication, direct speech (e.g., Mary said, "I'm hungry") is perceived as more vivid than indirect speech (e.g., Mary said that she was hungry). This vividness distinction has previously been found to underlie silent reading of quotations: Using functional magnetic resonance imaging (fMRI), we found that direct speech elicited higher brain activity in the temporal voice areas (TVA) of the auditory cortex than indirect speech, consistent with an "inner voice" experience in reading direct speech. Here we show that listening to monotonously spoken direct versus indirect speech quotations also engenders differential TVA activity. This suggests that individuals engage in top-down simulations or imagery of enriched supra-segmental acoustic representations while listening to monotonous direct speech. The findings shed new light on the acoustic nature of the "inner voice" in understanding direct speech. PMID- 22306806 TI - Imaging of lamination patterns of the adult human olfactory bulb and tract: in vitro comparison of standard- and high-resolution 3T MRI, and MR microscopy at 9.4 T. AB - PURPOSE: Neurological and smelling disorders (e.g. Alzheimer's disease, sinonasal disease) negatively affect the microstructural integrity of the olfactory bulb's (OB) cortical layers. Recovery processes depend on active restoration of this microstructural integrity enabled by neuroneogenesis in the OB. The aim of this study was to evaluate lamination patterns of the OB and adjacent tract (OT) using high resolution MRI at 3 Tesla (T) as well as MR microscopy at 9.4 T in comparison with histological sections. MATERIAL AND METHODS: Twenty-four human OBs were imaged in vitro using standard (2mm slice thickness) and high resolution (0.2mm slice thickness) T1w and T2w MR imaging at 3T. Based on signal intensity differences, the number of OB layers and the OB lamination patterns were assessed by two observers in consensus. Results were compared using Wilcoxon test. Signal intensity profiles were compared to reference Nissl stained histological sections and imaging results of MR microscopy. OT lamination patterns were assessed and different configurations of cross sectional areas were compared to macroscopic results and OB/OT lamination patterns. RESULTS: Standard resolution at 3T identified three layers in 8.3%, two layers in 83.3%, and one layer in 8.3%. High resolution at 3T (4 layers in 91.7%, 3 layers in 8.3%) significantly performed better (P<0.001). Signal intensity profile analysis at 3T and 9.4 T (yielding up to 6 different signal intensities) correlated with histological sections and enabled quantitative evaluation of OB lamination patterns. 3T MRI of the OT revealed two separate signal intensities in T2w in 73%, a hyperintense core and a hypointense sheath, and the number of OT signal intensities positively correlated (rho=0.541, P=0.006) with the increasing complexity of the OTs' cross sectional area configurations. Additionally, cross sectional area configurations correlated with macroscopic results (rho=0.558, P=0.002) and OB lamination patterns (rho=0.446, P=0.022). CONCLUSIONS: 3T MRI and MR-microscopy indicate the possibility to identify the lamination pattern of the human OB/OT and to reflect the histological status. If further development will be able to provide technical equipment that complies with the condition of human in vivo high resolution imaging achieving a good enough signal noise ratio, the method of signal intensity profile analysis could prospectively enable scientists to assess the OB's microstructural status in neurological and smelling disorders. PMID- 22306807 TI - Iridium phosphors with peripheral triphenylamine encapsulation: highly efficient solution-processed red electrophosphorescence. AB - The peripheral triphenylamine-encapsulated red-emitting iridium(III) complexes have been designed and synthesized. External quantum efficiency over 15% has been realized in single-layer polymer light-emitting diodes, which is the highest ever reported for solution-processed red phosphorescence. PMID- 22306808 TI - Polyubiquitin-sensor proteins reveal localization and linkage-type dependence of cellular ubiquitin signaling. AB - Polyubiquitin chain topology is thought to direct modified substrates to specific fates, but this function-topology relationship is poorly understood, as are the dynamics and subcellular locations of specific polyubiquitin signals. Experimental access to these questions has been limited because linkage-specific inhibitors and in vivo sensors have been unavailable. Here we present a general strategy to track linkage-specific polyubiquitin signals in yeast and mammalian cells, and to probe their functions. We designed several high-affinity Lys63 polyubiquitin-binding proteins and demonstrate their specificity in vitro and in cells. We apply these tools as competitive inhibitors to dissect the polyubiquitin-linkage dependence of NF-kappaB activation in several cell types, inferring the essential role of Lys63 polyubiquitin for signaling via the IL 1beta and TNF-related weak inducer of apoptosis (TWEAK) but not TNF-alpha receptors. We anticipate live-cell imaging, proteomic and biochemical applications for these tools and extension of the design strategy to other polymeric ubiquitin-like protein modifications. PMID- 22306809 TI - Interspecies activity correlations reveal functional correspondence between monkey and human brain areas. AB - Evolution-driven functional changes in the primate brain are typically assessed by aligning monkey and human activation maps using cortical surface expansion models. These models use putative homologous areas as registration landmarks, assuming they are functionally correspondent. For cases in which functional changes have occurred in an area, this assumption prohibits to reveal whether other areas may have assumed lost functions. Here we describe a method to examine functional correspondences across species. Without making spatial assumptions, we assessed similarities in sensory-driven functional magnetic resonance imaging responses between monkey (Macaca mulatta) and human brain areas by temporal correlation. Using natural vision data, we revealed regions for which functional processing has shifted to topologically divergent locations during evolution. We conclude that substantial evolution-driven functional reorganizations have occurred, not always consistent with cortical expansion processes. This framework for evaluating changes in functional architecture is crucial to building more accurate evolutionary models. PMID- 22306810 TI - Library-free methylation sequencing with bisulfite padlock probes. AB - Targeted quantification of DNA methylation allows for interrogation of the most informative loci across many samples quickly and cost-effectively. Here we report improved bisulfite padlock probes (BSPPs) with a design algorithm to generate efficient padlock probes, a library-free protocol that dramatically reduces sample-preparation cost and time and is compatible with automation, and an efficient bioinformatics pipeline to accurately obtain both methylation levels and genotypes from sequencing of bisulfite-converted DNA. PMID- 22306811 TI - Systematic identification of gene annotation errors in the widely used yeast mutation collections. AB - The baker's yeast mutation collections are extensively used genetic resources that are the basis for many genome-wide screens and new technologies. Anecdotal evidence has previously pointed to the putative existence of a neighboring gene effect (NGE) in these collections. NGE occurs when the phenotype of a strain carrying a particular perturbed gene is due to the lack of proper function of its adjacent gene. Here we performed a large-scale study of NGEs, presenting a network-based algorithm for detecting NGEs and validating software predictions using complementation experiments. We applied our approach to four datasets uncovering a similar magnitude of NGE in each (7-15%). These results have important consequences for systems biology, as the mutation collections are extensively used in almost every aspect of the field, from genetic network analysis to functional gene annotation. PMID- 22306812 TI - Oxidative stress increases BACE1 protein levels through activation of the PKR eIF2alpha pathway. AB - Beta-site APP cleaving enzyme 1 (BACE1) is the rate limiting enzyme for accumulation of amyloid beta (Abeta)-peptide in the brain in Alzheimer's disease (AD). Oxidative stress (OS) that leads to metabolic dysfunction and apoptosis of neurons in AD enhances BACE1 expression and activity. The activation of c-jun N terminal kinase (JNK) pathway was proposed to explain the BACE1 mRNA increase under OS. However, little is known about the translational control of BACE1 in OS. Recently, a post-transcriptional increase of BACE1 level controlled by phosphorylation of eIF2alpha (eukaryotic translation initiation factor-2alpha) have been described after energy deprivation. PKR (double-stranded RNA dependant protein kinase) is a pro-apoptotic kinase that phosphorylates eIF2alpha and modulates JNK activation in various cellular stresses. We investigated the relations between PKR, eIF2alpha and BACE1 in AD brains in APP/PS1 knock-in mice and in hydrogen peroxide-induced OS in human neuroblastoma (SH-SY5Y) cell cultures. Immunoblotting results showed that activated PKR (pPKR) and activated eIF2alpha (peIF2alpha) and BACE1 levels are increased in AD cortices and BACE1 correlate with phosphorylated eIF2alpha levels. BACE1 protein levels are increased in response to OS in SH-SY5Y cells and specific inhibitions of PKR eIF2alpha attenuate BACE1 protein levels in this model. Our findings provide a new translational regulation of BACE1, under the control of PKR in OS, where eIF2alpha phosphorylation regulates BACE1 protein expression. PMID- 22306813 TI - Structural characteristics of genomic islands associated with GMP synthases as integration hotspot among sequenced microbial genomes. AB - tRNA, tmRNA and some small RNA genes are recognized as general integration hotspots of genomic islands (GIs). The GMP synthase gene (guaA) has been firstly identified as one insertion hotspot of foreign DNA fragments. Thirty four islands integrated into the guaA genes were identified in the 987 completely sequenced archaeal and bacterial genomes. These alien islands were widely distributed within the host strains belonging to Proteobacteria, Firmicutes and Actinobacteria. The analysis of structural characteristics of these GIs is important for further determination of the island mobility and transference into suitable hosts. The putative functional integrases encoded by guaA-associated islands were mainly composed of phage P4 integrases, and followed by phage PhiLC3 integrases. Interestingly, island-encoding AlpA is close to P4 integrase and is deduced to be the positive transcriptional regulatory factor of P4 integrase while the XRE protein is close to PhiLC3 integrase and may be the negative transcriptional regulatory factor of PhiLC3 integrase. An 8-bp consensus sequence (5'-GAGTGGGA-3') within the direct repeats of these GIs is the cutting site of the P4 integrases encoding by guaA-associated islands, in which the third nucleotide (G) is the key site. The large-scale investigation of the content of GMP synthase gene hotspots may be useful to find important functional islands within members of many key bacterial species and to transfer useful islands into more suitable hosts. PMID- 22306814 TI - Phylogenetic analysis of 626 hepatitis E virus (HEV) isolates from humans and animals in China (1986-2011) showing genotype diversity and zoonotic transmission. AB - Hepatitis E is considered as a public health problem in China. To determine the overall molecular epidemiology of hepatitis E virus (HEV) and analyze the situation of cross-species transmission between humans and swine in China over the last 25 years (1986-2011), 626 HEV complete and partial sequences (89 isolates identified by our group) isolated from humans and animals in China were retrieved from GenBank and subjected to phylogenetic analysis. There were three genotypes and 11 sub-genotypes of HEV prevailing in China. Furthermore, rabbit HEVs, of which the genotype is controversial, are also widespread in China. Genotype 1 was the most isolated genotype prior to 2000 and mainly detected in Xinjiang, Beijing and East China. However, genotype 4, which was identified in most regions of China during the last 10 years, has overtaken genotype 1 in frequency of isolation nationwide. Genotype 3 HEV strains have been found only in eastern China and were thought to be imported from Japan. Both genotypes 3 and 4 were found in humans and swine and cross-species transmission from pigs to humans of the two genotypes may have occurred in Northeast, Northwest, North, East and South China. These results indicate that HEV strains with considerable genetic diversity are widespread and the zoonotic transmission between swine and humans appears ubiquitous in China. PMID- 22306815 TI - Ascariasis in people and pigs: new inferences from DNA analysis of worm populations. AB - Ascaris is a large parasitic roundworm (nematode) of the small intestine of humans and pigs. These roundworms cause the socioeconomically important disease, ascariasis. For the past 20 years, molecular markers have been used in studies on Ascaris and ascariasis, and added valuable information to the understanding of these roundworms. Here, we provide a review of these studies on human and pig roundworms. We begin with a summary of studies using molecular phenotypic markers to compare Ascaris from humans and pigs, followed by a synopsis of comparisons using genetic markers. We then draw forth inferences in the aspects of host affiliation and infection success, transmission between and among humans and pigs, evolutionary history of Ascaris. We also highlight additional topics such as mating dynamics, diagnostics, and paleoparasitology where molecular epidemiological approaches have been utilized. PMID- 22306816 TI - Ticagrelor induces adenosine triphosphate release from human red blood cells. AB - RATIONALE: The novel P2Y(12) antagonist ticagrelor inhibits ADP-induced platelet aggregation more rapidly and more potently than clopidogrel. Clinical trials have revealed dyspnea and asymptomatic ventricular pauses as side effects of ticagrelor. The mechanism behind these side effects is not known, but it is plausible that they are mediated by adenosine. OBJECTIVE: Ticagrelor is known to increase adenosine concentrations by inhibiting red blood cell reuptake, but the potency of this effect may be too low to fully explain the adenosine related effects. The purpose of the present study was to determine whether ticagrelor has other effects on red blood cells (RBCs) that could contribute to explain the pleiotropic effects seen with ticagrelor treatment. METHODS AND RESULTS: Using a luciferase-based bioluminescence assay, we studied ATP release in human blood. Human RBCs responded to ticagrelor in vitro by releasing substantial amounts of ATP in a dose-dependent manner (IC(50) 14MUM). The rapid effect indicates release through membrane channels, which was supported by a depolarizing effect of ticagrelor and inhibition of ATP release by anion channel blockers. CONCLUSION: In conclusion, our data show that, in vitro, ticagrelor can induce ATP release from human RBCs, which is subsequently degraded to adenosine. Further studies are warranted to determine what role this mechanism may play in the clinical effects of ticagrelor. PMID- 22306817 TI - MicroRNAs regulate osteogenesis and chondrogenesis. AB - MicroRNAs (miRNAs) are a class of small molecules and non-coding single strand RNAs that regulate gene expression at the post-transcriptional level by binding to specific sequences within target genes. miRNAs have been recognized as important regulatory factors in organism development and disease expression. Some miRNAs regulate the proliferation and differentiation of osteoblasts, osteoclasts and chondrocytes, eventually influencing metabolism and bone formation. miRNAs are expected to provide potential gene therapy targets for the clinical treatment of metabolic bone diseases and bone injuries. Here, we review the recent research progress on the regulation of miRNAs in bone biology, with a particular focus on the miRNA-mediated control mechanisms of bone and cartilage formation. PMID- 22306818 TI - Effects of strontium on proliferation and differentiation of rat bone marrow mesenchymal stem cells. AB - Strontium ranelate (SrR) was an effective anti-osteoporotic drug to increase bone formation and decrease bone resorption. However, reports about the effect of SR on osteoblastic and adipocytic differentiation from bone marrow mesenchymal stem cells (BMMSCs) are limited. The purpose of this study is to evaluate whether SrR affects the ability of BMMSCs to differentiate into osteoblasts or adipocytes. Rat BMMSCs were identified by flow cytometry and exposed to SR (0.1 and 1.0mMSr(2+)) under osteogenic or adipogenic medium for 1 and 2weeks. The proliferation and differentiation of BMMSCs were analyzed by MTT, alkaline phosphatase (ALP), Oil red O staining, quantitative real-time RT-PCR and Western blot assays. SrR significantly inhibited the proliferation, increased osteoblastic but decreased adipocytic differentiation of rat BMMSCs dose dependently. In osteogenic medium, SrR increased the expression of ALP, the mRNA levels of Cbfa1/Runx2, bone sialoprotein, and osteocalcin by RT-PCR, and the protein levels of Cbfa1/Runx2 by Western blot. In adipogenic medium, SrR decreased the mRNA levels of PPARgamma2, adipocyte lipid-binding protein 2 (aP2/ALBP), and lipoprotein lipase (LPL) by RT-PCR, and the protein expression of PPARgamma in Western blot analysis. These results indicated that the effects of SrR to promote osteoblastic but inhibit adipocytic differentiation of BMMSCs might contribute to its effect on osteoporosis treatment. PMID- 22306819 TI - NAD-dependent histone deacetylase, SIRT1, plays essential roles in the maintenance of hematopoietic stem cells. AB - Sir2 has been shown to be essential for transcriptional silencing and longevity provided by calorie restriction in Saccharomyces cerevisiae and Caenorhabditis elegans. In this study, we investigated the role for its mammalian homologue, SIRT1, in hematopoietic cells. SIRT1 inhibitor, nicotinamide (NA), promoted and its activator, resveratrol, inhibited the differentiation of murine bone marrow c Kit(high)Sca-1(+)Lineage(-) (KSL) cells during the culture system ex vivo. To further clarify the roles of SIRT1 in hematopoietic cells, we isolated KSL cells from fetal liver of SIRT1 knockout (KO) mice and cultured them for 5days, because SIRT1 KO mice die shortly after the delivery. In agreement with the results from the experiments using NA and resveratrol, KSL cells isolated from SIRT1 KO mice more apparently differentiated and lost the KSL phenotype than those from wild type (WT) mice. Furthermore, in each of colony assay, replating assay, or serial transplantation assay, SIRT1 KO KSL cells lost earlier the characteristics of stem cells than WT KSL cells. In addition, we found that SIRT1 maintains prematurity of hematopoietic cells through ROS elimination, FOXO activation, and p53 inhibition. These results suggest that SIRT1 suppresses differentiation of hematopoietic stem/progenitor cells and contributes to the maintenance of stem cell pool. PMID- 22306820 TI - Hainanenins: a novel family of antimicrobial peptides with strong activity from Hainan cascade-frog, Amolops hainanensis. AB - Antimicrobial peptides (AMPs) secreted by amphibian skin represent an important innate immune defense strategy. There are more than 340 species in the family of Ranidae worldwidely, and from which nearly 100 families of AMPs comprising between 8 and 48 amino acid (aa) residues have been characterized. In current work, two novel AMPs were purified from the skin secretion of Hainan cascade frog, Amolops hainanensis, and 31 cDNA sequences encoding 10 novel AMPs belonging to 4 families were cloned from the constructed skin cDNA library of A. hainanensis. Among these 10 AMPs, 5 peptides represent the prototypes of a novel amphibian AMP family. According to the generic name of the species of origin, they were designated as hainanenin-1-5. Each of them consists of 21 aa residues with a C-terminal disulphide loop of 7 residues between Cys(15) and Cys(21). Two of them (hainanenin-1 and 5) were then synthesized and their in vitro activities were screened, including antimicrobial, hemolytic and antioxidant activities. The results showed that hainanenin-1 and 5 possessed strong and broad-spectrum antimicrobial activities against Gram-positive, Gram-negative bacteria and fungi, including a large number of clinically isolated drug-resistant pathogenic microorganisms, and slight antioxidant activity. Undesirably, hainanenin-1 and 5 exhibited strong hemolytic activity on human erythrocytes. The discovery of hainanenins and their great antimicrobial potency provides new templates for anti infective agent design. PMID- 22306821 TI - Threats to moral self-perceptions trigger obsessive compulsive contamination related behavioral tendencies. AB - BACKGROUND AND OBJECTIVES: Obsessive compulsive (OC) phenomena such as contamination fears may lead to significant impairment in daily functioning. In this research, we examined whether threat to moral self-perceptions can trigger contamination-related behavioral tendencies. METHOD: Three experiments examined the influence of subtle priming of morality-related information on contamination related behavioral tendencies. RESULTS: Subtle suggestions of incompetence in the morality self-domain led to heightened OC-related behavioral tendencies. These effects were specific to self-relevant (versus other-relevant), negative (versus positive) information about the morality domain (versus a morality-irrelevant domain). Findings were not related to pre-existing variations in self-esteem, stress, anxiety, or depression, and were not explained by mood fluctuations. LIMITATIONS: Our studies were conducted with non-clinical samples. CONCLUSIONS: Self-sensitivities in the moral domain may be causally linked with contamination related concerns. Treatments addressing such sensitivities may prove useful when treating obsessive compulsive phenomena. PMID- 22306822 TI - Parasites reveal movement of bats between the New and Old Worlds. AB - The global distribution of bat taxa indicates that the Atlantic and Pacific Oceans are effective barriers to movement between the Old and New Worlds. For instance, one of the major suborders, Yinpterochiroptera, has an exclusively Old World distribution, and within the other, Yangochiroptera, no species and only five genera are common to both. However, as bats are sometimes blown out to sea, and have colonised isolated islands, occasional natural movement between the New and Old Worlds does appear to be possible. Here we identify new genotypes of a blood parasite, Trypanosoma dionisii, in Old World bats that are closely related to South American strains. Using highly conservative calibration points, divergence of Old and New World strains is estimated to have occurred 3.2-5.0 million years ago (MYA), depending on the method used (upper 95% CL for maximum time 11.4MYA). The true date of divergence is likely to be considerably more recent. These results demonstrate that taxon-specific parasites can indicate historical movements of their hosts, even where their hosts may have left no lasting phylogenetic footprint. PMID- 22306823 TI - Population genetic structure and geographic differentiation in the hot spring snake Thermophis baileyi (Serpentes, Colubridae): indications for glacial refuges in southern-central Tibet. AB - The endangered hot spring snake (Thermophis baileyi) is endemic to the Tibetan Plateau and restricted to a few sites at high altitudes (>3500 m a.s.l.). Its strong preference for habitats with hot springs might be an early adaptation to the cooling climate during the plateau uplift. Some of these thermal sites may have been free of ice during the last glacial maximum (LGM) serving as refuges for the snake. To test this and to examine the population genetic structure data of 12 microsatellites and mitochondrial DNA were obtained from 153 individuals from 12 sites across the plateau. Four of the microsatellite loci were newly developed for this study. The results suggest that T. baileyi has at least two genetically diverse clades in Tibet, which developed during the Pleistocene and expanded after the LGM. Accordingly, the existence of separate glacial refuges on the central plateau can be assumed. Analyses of the genetic variation indicated a high level of geographic differentiation and population structure on a regional as well as on a range-wide scale. The study shows that, apart from the phylogeographic signatures, the diversification of current Thermophis populations is caused by (a) a limited dispersal due to mountain ranges, (b) a strong preference for hot springs and (c) the insular distribution of suitable habitats on the plateau. The present data should be taken into account in necessary monitoring and management plans for T. baileyi. PMID- 22306824 TI - E value cutoff and eukaryotic genome content phylogenetics. AB - Genome content analysis has been used as a source of phylogenetic information in large prokaryotic tree of life studies. Recently the sequencing of many eukaryotic genomes has allowed for the similar use of genome content analysis for these organisms too. In this communication we examine the utility of genome content analysis for recovering phylogenetic patterns in several eukaryotic groups. By constructing multiple matrices using different e value cutoffs we examine the dynamics of altering the e value cutoff on five eukaryotic genome data sets. Our analysis indicates that the e value cutoff that is used as a criterion in the construction of the genome content matrix is a critical factor in both the accuracy and information content of the analysis. Strikingly, genome content by itself is not a reliable or accurate source of characters for phylogenetic analysis of the taxa in the five data sets we analyzed. We discuss two problems--small genome attraction and genome duplications as being involved in the rather poor performance of genome content data in recovering eukaryotic phylogeny. PMID- 22306825 TI - Gel microstructure regulates proliferation and differentiation of MC3T3-E1 cells encapsulated in alginate beads. AB - For cell transplantation into damaged tissues, viable cells must be delivered to the defect site in a suitable carrier. However, the hypoxic and nutrient-limited environment in the carrier can induce massive cell death. The aims of this study were to increase the viability and regulate the behavior of osteoprogenitor cells encapsulated in alginate hydrogels through control of the gel microstructure. Cell survivability in alginate beads was improved through the use of alpha-MEM as the solvent for alginic acid sodium salt, and by CaCl(2) solutions, which supplied additional nutrients for the cells compared to water or buffer. The mesh size and shear modulus of the hydrogel were hypothesized to regulate proliferation and differentiation of osteoprogenitor cells. MC3T3-E1 cells demonstrated enhanced osteoblast differentiation when encapsulated in high density alginate with smaller mesh size and more rigid mechanical properties, as confirmed by increased alkaline phosphatase activity and osteocalcin secretion. However, MC3T3-E1 cells encapsulated in low-density alginate beads with a larger mesh size and more compliant mechanical properties exhibited increased proliferation. These results demonstrate that the microstructure of alginate hydrogels can regulate the behavior of osteoprogenitor cells, thus suggesting that the tuning the properties of the gel may be a useful approach for enhancing new bone formation. PMID- 22306826 TI - Near and far space neglect: task sensitivity and anatomical substrates. AB - Most group studies which have investigated neglect for near and far space have found an increased severity of symptoms in far space compared to near space. However, the majority of these studies used relatively small samples and based their findings almost exclusively on line bisection performance. The aim of the present study was, therefore, to explore the occurrence of neglect for near and far space in a larger group of unselected right brain damaged patients and to evaluate whether neglect specific to near and far space is a task-related deficit or generalises across distance irrespective of task. In addition, a lesion overlap analysis was carried out to identify critical lesion sites associated with distance specific neglect deficits. Thirty-eight right hemisphere damaged patients carried out a line bisection and a cancellation task by using a pen in near space (40 cm) and a laser pointer in far space (320 cm). The results showed that both the number of left-sided omissions and rightward bisection errors were significantly increased in near compared to far space. Distance specific dissociations, albeit less common, were more frequently observed for cancellation than line bisection. These results suggest that space representation in neglect is more severely impaired in near than in far space. In addition, distance related dissociations in neglect may depend on task demands. Although the anatomical findings were broadly consistent with a dorsal and ventral stream dichotomy for near and far space processing, they also suggest the involvement of intermediate structures in distance related neglect phenomena. PMID- 22306827 TI - Nonylphenol induces apoptosis via mitochondria- and Fas-L-mediated pathways in the liver of adult male rat. AB - Nonylphenol (NP) is an environmental contaminant known to possess estrogenic properties. Humans are constantly exposed to NP by contaminated water and food products. In the present study we sought to investigate whether treatment with low doses of NP induces apoptosis in the liver of adult rats. Rats were administered with NP by oral gavage at the doses of 15,150 and 1500 MUg/kg body weight per day for 45 days. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assayed. Apoptosis-related proteins namely cytochrome c, caspase-3, caspase-8, caspase-9, Fas and Fas-l, and expression of bcl-2 mRNA and bax mRNA were examined in the liver. Levels of AST and ALT were increased in the treated rats. Western blot analysis revealed elevation in the levels of cytochrome c, caspase-3, caspase-8, caspase-9, Fas and Fas-l in the liver of NP treated rats. Decreased expression of bcl-2 mRNA (anti-apoptotic) and increased expression of bax mRNA (apoptotic) were observed in the liver of treated rats. Increased localization of caspase-3 in the hepatocytes and DNA damage were observed in the liver of treated rat. It is concluded that NP induces apoptosis in liver involving both mitochondria-dependent and Fas-Fas-l pathways and thereby, leading to hepatic damage in rats. PMID- 22306828 TI - The value of acute toxicity testing of pharmaceuticals for estimation of human response. AB - The determination of single high doses of active pharmaceutical ingredients (API) is used mostly to fulfill regulatory demands. Oral LD(50) values in animals for over 300 API were compared to the minimal effective therapeutic doses (METD) in humans in order to find a correlation between animal and human data. The highest correlation between human METD and animal LD(50) was found for the dog (R=0.323), the lowest for the rat (0.287). It was determined that acute oral LD(50) of rats have poor correlation with the METD, and cannot be used as a classification criteria into official acute toxic categories. Only 13% of API has been classified as fatal if swallowed according to the EU CLP regulation, none of the substances with very low therapeutic dose have been identified as EU CLP acute toxicity category 1. Substances with very low therapeutic doses, which could potentially have toxic effects in humans, are not identified with the use of oral LD(50) and current classification system. We propose that the acute toxicity based on rat LD(50) dose is not used as a basis for classification of pharmaceuticals, and that the METD is applied as basis for classification. PMID- 22306829 TI - Synthesis, docking studies and biological evaluation of benzo[b]thiophen-2-yl-3 (4-arylpiperazin-1-yl)-propan-1-one derivatives on 5-HT1A serotonin receptors. AB - A series of novel benzo[b]thiophen-2-yl-3-(4-arylpiperazin-1-yl)-propan-1-one derivatives 6a-f, 7a-f and their corresponding alcohols 8a-f were synthesized and evaluated for their affinity towards 5-HT(1A) receptors. The influence of arylpiperazine moiety and benzo[b]thiophene ring substitutions on binding affinity was studied. The most promising analogue, 1-(benzo[b]thiophen-2-yl)-3-(4 (pyridin-2-yl)piperazin-1-yl)propan-1-one (7e) displayed micromolar affinity (K(i) = 2.30 MUM) toward 5-HT(1A) sites. Docking studies shed light on the relevant electrostatic interactions which could explain the observed affinity for this compound. PMID- 22306830 TI - Supramolecular photodimerization of coumarins. AB - Stereoselective photodimerization of coumarin and its derivatives in supra molecular systems is reviewed. The enantioselective photodimerization of coumarin and thiocoumarin in inclusion crystals with optically active host compounds is also described. PMID- 22306831 TI - A new iridoid glycoside from the roots of Dipsacus asper. AB - A new iridoid glycoside, named loganic acid ethyl ester (1), together with five known compounds: chlorogenic acid (2), caffeic acid (3), loganin (4), cantleyoside (5) and syringaresinol-4',4''-O-bis-beta-D-glucoside (6) were isolated from the roots of Dipsacus asper. The structure of compound 1 was elucidated on the basis of detailed spectroscopic analyses. Lignan is isolated from Dipsacaceae species for the first time. Compounds 1, 4 and 5 had moderate neuroprotective effects against the Abeta25-35 induced cell death in PC12 cells. PMID- 22306832 TI - Total synthesis and antidepressant activities of laetispicine and its derivatives. AB - The first total synthesis of laetispicine (1a), an amide alkaloid isolated from the stems of Piper laetispicum C.DC (Piperaceae), and the synthesis of some of its derivatives were described. Based on the evaluation of antidepressant activities in the forced swimming test, compounds 1h and 1i were identified as potent and safe antidepressant lead compounds. PMID- 22306833 TI - Efficient one-pot multienzyme synthesis of UDP-sugars using a promiscuous UDP sugar pyrophosphorylase from Bifidobacterium longum (BLUSP). AB - A promiscuous UDP-sugar pyrophosphorylase (BLUSP) was cloned from Bifidobacterium longum strain ATCC55813 and used efficiently with a Pasteurella multocida inorganic pyrophosphatase (PmPpA) with or without a monosaccharide 1-kinase for one-pot multienzyme synthesis of UDP-galactose, UDP-glucose, UDP-mannose, and their derivatives. Further chemical diversification of a UDP-mannose derivative resulted in the formation of UDP-N-acetylmannosamine. PMID- 22306834 TI - BRCA testing is important for our patients. PMID- 22306835 TI - Critique of "Evidence-Based Surgical Hypothesis: The case against BRCA1 and 2 testing". PMID- 22306836 TI - Social media in low-resource settings: a role for Twitter and Facebook in global surgery? PMID- 22306837 TI - Recommendation for standardized surgical management of primary adrenocortical carcinoma. AB - BACKGROUND: Operative resection is the only potentially curative treatment for primary adrenocortical carcinoma (ACC), but standards of operative care are not defined with regards to the extent of local resection. We propose recommendations for operative management. METHODS: Anatomic and clinical literature review focusing on local management of ACC, including lymphadenectomy and resection of adjacent organs or large vessels. RESULTS: First-order drainage nodes of the adrenal gland include the renal hilum lymph nodes, the celiac lymph nodes, and the para-aortic and paracaval lymph nodes, mainly above the renal pedicle and ipsilateral to the adrenal glands. Lymph node involvement occurs in about 20% of patients with ACC, and is an important prognostic factor, but lymphadenectomy is performed infrequently. The adrenal glands and kidneys are contained in the same anatomic space, but systematic en bloc nephrectomy has no proven benefits for survival. Direct invasion of the kidney or adjacent organs is rare, but major venous invasion with tumor thrombus is relatively common. Both are associated with decreased survival, but complete resection can lead to long-term survival. CONCLUSION: Standardization of regional lymphadenectomy including first-order drainage nodes is proposed. Systematic nephrectomy is not necessary in the absence of gross local invasion, but locally involved organs or large veins should be resected en bloc, with tumor thrombus embolectomy, if R0 resection is possible. Operative standardization improves tumor staging, potentially decreases local recurrence, and may be associated with better survival. Evidence-based standards of operative care and prospective investigations within international collaborating groups are necessary. PMID- 22306838 TI - Liver resection for liver metastases from nondigestive endocrine cancer: extrahepatic disease burden defines outcome. AB - BACKGROUND: For patients with hepatic nondigestive endocrine metastases (HNEM), the role of liver resection is not well-defined. METHODS: We reviewed outcomes for patients who underwent liver resection for HNEM at 2 centers to identify predictors of survival. RESULTS: From 1991 to 2010, 51 patients underwent liver resection for HNEM. Primary tumor types were adrenal gland (n = 26), thyroid (n = 11), testicular germ cell (n = 9), and ovarian granulosa cell (n = 5). 28 patients (55%) had synchronous or early (diagnosed within 12 months after primary tumor resection) liver metastases. At liver resection, 26 patients (51%) had extrahepatic metastases, and 7 (14%) had >=2 sites of extrahepatic metastases. 32 patients (63%) had major liver resection and 19 (37%) had a simultaneous extrahepatic procedure. 90-day postoperative morbidity and mortality rates were 27% and 2%, respectively. After median follow-up of 20 months (range, 1-144), the 5-year overall and recurrence-free survival rates were 58% and 37%, respectively. Survival was not affected by primary tumor type. In multivariate analysis, >=2 sites of extrahepatic metastases (hazard ratio [HR] = 4.80; 95% confidence interval [CI] = 1.18-19.50; P = .028) and interval of <=12 months between primary tumor resection and diagnosis of liver metastases (HR = 5.33; 95% CI = 1.11 25.71; P = .037) were associated with worse overall survival after liver resection. CONCLUSION: For selected patients, liver resection for HNEM is associated with long-term survival. The number of extrahepatic sites of metastasis and the timing of appearance of liver metastases should be considered in patient selection. PMID- 22306839 TI - Direct observation of the spin-dependent Peltier effect. AB - The Peltier coefficient describes the amount of heat that is carried by an electrical current when it passes through a material. When two materials with different Peltier coefficients are placed in contact with one another, the Peltier effect causes a net flow of heat either towards or away from the interface between them. Spintronics describes the transport of electric charge and spin angular momentum by separate spin-up and spin-down channels in a device. The observation that spin-up and spin-down charge transport channels are able to transport heat independently of each other has raised the possibility that spin currents could be used to heat or cool the interface between materials with different spin-dependent Peltier coefficients. Here, we report the direct observation of the heating and cooling of such an interface by a spin current. We demonstrate this spin-dependent Peltier effect in a spin-valve pillar structure that consists of two ferromagnetic layers separated by a non-ferromagnetic metal. Using a three-dimensional finite-element model, we extract spin-dependent Peltier coefficients in the range -0.9 to -1.3 mV for permalloy. The magnetic control of heat flow could prove useful for the cooling of nanoscale electronic components or devices. PMID- 22306840 TI - Tunable doping of a metal with molecular spins. AB - The mutual interaction of localized magnetic moments and their interplay with itinerant conduction electrons in a solid are central to many phenomena in condensed-matter physics, including magnetic ordering and related many-body phenomena such as the Kondo effect, the Ruderman-Kittel-Kasuya-Yoshida interaction and carrier-induced ferromagnetism in diluted magnetic semiconductors. The strength and relative importance of these spin phenomena are determined by the magnitude and sign of the exchange interaction between the localized magnetic moments and also by the mean distance between them. Detailed studies of such systems require the ability to tune the mean distance between the localized magnetic moments, which is equivalent to being able to control the concentration of magnetic impurities in the host material. Here, we present a method for doping a gold film with localized magnetic moments that involves depositing a monolayer of a metal terpyridine complex onto the film. The metal ions in the complexes can be cobalt or zinc, and the concentration of magnetic impurities in the gold film can be controlled by varying the relative amounts of cobalt complexes (which carry a spin) and zinc complexes (which have zero spin). Kondo and weak localization measurements demonstrate that the magnetic impurity concentration can be systematically varied up to ~800 ppm without any sign of inter-impurity interaction. Moreover, we find no evidence for the unwanted clustering that is often produced when using alternative methods. PMID- 22306841 TI - Charity's decision to cut funding to Planned Parenthood sparks controversy. PMID- 22306842 TI - Training can help GPs provide a better death for patients. PMID- 22306843 TI - Cancer charity rates TV shows in terms of junk food advertising. PMID- 22306844 TI - Nitric oxide donor and non steroidal anti inflammatory drugs as a therapy for muscular dystrophies: evidence from a safety study with pilot efficacy measures in adult dystrophic patients. AB - This open-label, single centre pilot study was designed to evaluate safety and tolerability of the combination of the drugs isosorbide dinitrate, a nitric oxide donor, and ibuprofen, a non steroid anti-inflammatory drug, in a cohort of adult dystrophic patients (Duchenne, Becker and Limb-Girdle Muscular Dystrophy). Seventy-one patients were recruited: 35, treated with the drug combination for 12 months, and 36 untreated. Safety and adverse events were assessed by reported signs and symptoms, physical examinations, blood tests, cardiac and respiratory function tests. Exploratory outcomes measure, such as the motor function measure scale, were also applied. Good safety and tolerability profiles of the long-term co-administration of the drugs were demonstrated. Few and transient side effects (i.e. headache and low blood pressure) were reported. Additionally, exploratory outcomes measures were feasible in all the disease population studied and evidenced a trend towards amelioration that reached statistical significance in one dimension of the MFM scale. Systemic administration of ibuprofen and isosorbide dinitrate provides an adequate safety margin for clinical studies aimed at assessing efficacy. PMID- 22306845 TI - Novel LDL-oriented pharmacotherapeutical strategies. AB - Elevated levels of low-density cholesterol (LDL-C) are highly correlated with increased risk of cardiovascular diseases (CVD). Thus, current guidelines have recommended progressively lower LDL-C for cholesterol treatment and CVD prevention as the primary goal of therapy. Even so, some patients in the high risk category fail to achieve recommended LDL-C targets with currently available medications. Thereby, additional pharmaceutical strategies are urgently required. In the review, we aim to provide an overview of both current and emerging LDL-C lowering drugs. As for current available LDL-C lowering agents, attentions are mainly focused on statins, niacin, bile acid sequestrants, ezetimibe, fibrates and omega-3 fatty acids. On the other hand, the emerging drugs differ from mechanisms are including: intervention of cholesterol biosynthesis downstream enzyme (squalene synthase inhibitors), inhibition of lipoprotein assembly (antisense mRNA inhibitors of apolipoprotein B and microsomal transfer protein inhibitors), enhanced lipoprotein clearance (proprotein convertase subtilisin kexin type 9, thyroid hormone analogues), inhibition of intestinal cholesterol absorption (Niemann-Pick C1-like 1 protein and acyl coenzyme A:cholesterol acyltransferase inhibitors) and interrupting enterohepatic circulation (apical sodium-dependent bile acid transporter inhibitors). Several ongoing agents are in their different stages of clinical trials, in expectation of promising antihyperlipidemic drugs. Therefore, alternative drugs monotherapy or in combination with statins will be sufficient to reduce LDL-C concentrations to optimal levels, and a new era for better LDL-C managements is plausible. PMID- 22306846 TI - Vitamin D receptor and Alzheimer's disease: a genetic and functional study. AB - Genetic studies on late-onset Alzheimer's disease (AD) have repeatedly mapped susceptibility loci onto chromosome 12q13, encompassing the vitamin D receptor (VDR) gene. Epidemiology studies have indicated vitamin D insufficiency as a risk factor for AD. Given that VDR is the major mediator for vitamin D's actions, we sought to clarify the role of VDR in late-onset AD. We conducted an association study in 492 late-onset AD cases and 496 controls with 80 tagging single nucleotide polymorphisms (SNPs). The strongest association was found at a promoter SNP rs11568820 (P = 9.1 * 10(-6), odds ratio (OR) = 1.69), which resides within the transcription factor Cdx-2 binding site and the SNP has been also known as CDX2. The risk-allele at rs11568820 is associated with lower VDR promoter activity (p < 10(-11)). The overexpression of VDR or vitamin D treatment suppressed amyloid precursor protein (APP) transcription in neuroblastoma cells (p < 0.001). We provide both statistical evidence and functional data suggesting VDR confers genetic risk for AD. Our findings are consistent with epidemiology studies suggesting that vitamin D insufficiency increases the risk of developing AD. PMID- 22306847 TI - AMP-activated protein kinase activator AICAR acutely lowers blood pressure and relaxes isolated resistance arteries of hypertensive rats. AB - OBJECTIVES: AMP-activated protein kinase (AMPK) activity may alter blood pressure by directly influencing vascular tone. The purpose of this study is to examine if these effects occur acutely in a model of hypertension. METHODS AND RESULTS: Using distinct groups of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) we compare baseline aortic and mesenteric artery AMPK activation (by immunoblotting), hemodynamic (blood pressure and heart rate via carotid catheter) and biochemical responses to an acute injection of AMPK activator 5 aminoimidazole-4-carboxyamide-1-beta-D-ribofuranoside (AICAR) in vivo and vasomotor responses of isolated mesenteric vessels to AICAR exposure in vitro using myography. Mean arterial pressure (MAP) decreased from 196 +/- 3 to 122 +/- 15 mmHg (P < 0.001) during the 30 min following AICAR injection in SHR (an effect partially prevented by NOS inhibitor L-NAME), but in WKY MAP was unaffected by AICAR. Basal AMPK activation (phosphorylation of AMPK activation site threonine 172) was reduced by approximately 50% in aorta of SHR vs. WKY (0.49 +/- 0.1 vs. 1.0 +/- 0.1 arbitrary units, P < 0.001), and was improved approximately 1.6-fold in SHR but not in WKY aorta 30 min following AICAR injection. In isolated vessel experiments, dose-dependent vasorelaxation to AICAR was similar in mesenteric arteries of SHR and WKY, although responses were more reliant on nitric oxide in SHR vs. WKY. CONCLUSIONS: The ability of AICAR to improve vascular AMPK activation, and to generate parallel reductions in blood pressure and relaxation of SHR resistance vasculature, highlights the potential importance of AMPK in the regulation of blood pressure and vascular tone. PMID- 22306848 TI - Overexpression of coupling factor 6 attenuates exercise-induced physiological cardiac hypertrophy by inhibiting PI3K/Akt signaling in mice. AB - BACKGROUND: Regular exercise improves systolic cardiac dysfunction through Akt cascade-mediated physiological hypertrophy in congestive heart failure. Tissue acidosis impairs Akt cascade, and coupling factor 6 induces tissue acidosis via activation of ecto-F(1)F(o) complex. We tested the hypothesis that coupling factor 6 attenuates physiological cardiac hypertrophy induced by exercise and its benefit in mice. METHODS AND RESULTS: Adult wild-type mice (n = 20) and coupling factor 6-overexpressing transgenic mice (n = 20) were divided into two groups with or without 4-week exercise consisting of 90-min swimming twice daily. Left ventricular posterior wall and interventricular septum thicknesses were increased by 0.12 +/- 0.1 and 0.16 +/- 0.1 mm, respectively, after 4-week swimming in wild type mice (both P < 0.01), but unchanged in transgenic mice. Fractional shortening was increased from 37 +/- 1 to 41 +/- 1% after 4-week swimming in wild type mice (P < 0.05), whereas it was unchanged in transgenic. The insulin-like growth factor 1 (IGF-1) receptor protein and its phosphorylated form in the heart were both increased by 1.83 +/- 0.23 and 1.83 +/- 0.09 times, respectively, after 4-week swimming in wild-type mice (both P < 0.05), but were unchanged in transgenic. Downstream phosphoinsulin receptor substrate 1, phosphoinositide 3 kinase, and phospho-Akt were increased by 2.22 +/- 0.22, 1.78 +/- 0.31, and 2.24 +/- 0.49 times, respectively, in wild-type mice (all P < 0.05), but were unchanged in transgenic. Restoration of phospho-Akt by IGF-1 injection recovered left ventricular hypertrophy and systolic function after 4-week swimming in transgenic. CONCLUSION: Overexpression of coupling factor 6 attenuates exercise induced physiological cardiac hypertrophy by downregulating Akt signaling, thereby cancelling its benefit for cardiac function in mice. Reduction in coupling factor 6 level seems to be useful for drawing the exercising effects on cardiac function. PMID- 22306849 TI - A new tool to assess retinal vessel caliber. Reliability and validity of measures and their relationship with cardiovascular risk. AB - OBJECTIVE: To analyze the reliability and validity of a semiautomated tool for assessing retinal vessel caliber and to describe the relationship of measures taken to cardiovascular risk and target organ damage. METHODS: A total of 210 patients aged 34-75 years were selected with retinography. Retinal photographs were digitized, and superior and inferior temporal vessels were measured in an area 0.5-1 disk diameter from the optic disc with semiautomated software [arteriole/venule index (AVIx) calculator]. AVIx was also estimated. Vascular damage was assessed using carotid intima-media thickness and pulse wave velocity, cardiac damage using Cornell voltage-duration product, renal damage using the glomerular filtration rate and microalbuminuria, and cardiovascular risk with the Framingham score. RESULTS: Interobserver intraclass correlation coefficient (ICC) ranged from 0.96 [95% confidence interval (CI) 0.94-0.97] to 0.99 (95% CI 0.98 0.99), and intraobserver ICC ranged from 0.97 (95% CI 0.94-0.98) to 0.99 (95% CI 0.99-0.99). In the Bland-Altman plot, the limit of interobserver agreement was 0.009 (0.066 to -0.086) in right AVIx and -0.001 (0.083 to -0.085) in left AVIx, whereas the limit of intraobserver agreement for overall AVIx was -0.005 (-0.057 to -0.047). Cardiovascular risk and albumin-creatinine ratio were higher in the first tertile of AVIx as compared with the other two (P < 0.05). In multiple regression, AVIx and venule caliber, but not artery caliber, behaved as predictors of cardiovascular risk and microalbuminuria. CONCLUSION: This tool showed a high intraobserver and interobserver reliability, and results of the validity analysis agree with those from large studies in estimation of cardiovascular risk and evaluation of target organ damage. PMID- 22306851 TI - Changes in blood pressure and systemic vascular resistance do not predict microvascular structure during treatment of mild essential hypertension. AB - BACKGROUND: Essential hypertension is characterized by small artery remodeling and increased systemic vascular resistance (SVR). We hypothesized that changes in SVR index (SVRI) were associated with measures of small artery structure as reflected by minimum coronary and forearm vascular resistance (C-Rmin and F-Rmin, respectively). Also, we investigated how F-Rmin is related to C-Rmin, coronary flow reserve (CFR), left ventricular mass index (LVMI) and blood pressure (BP). METHOD: Sixty-six never-treated patients with uncomplicated mild essential hypertension had the following measured at baseline: 24-h blood BP, LVMI, CFR and C-Rmin (echocardiography), F-Rmin (forearm plethysmography) and SVRI determined by a gas re-breathing method. After 6 months of antihypertensive therapy administered by the general practitioner, the patients returned for follow-up measurements. RESULTS: Changes in SVRI did not correlate to changes in F-Rmin (r = 0.001, P = 0.98) or C-Rmin (r = 0.13, P = 0.39) but did correlate to changes in CFR (r = 0.30, P = 0.04). Further analysis was performed by assigning the patients into two groups according to the median of drop in F-Rmin. When adjusted in a multivariate model, changes in F-Rmin (-8.1 +/- 3.2%) were significantly associated with changes in C-Rmin (-9.3 +/- 4.9%) and LVMI (-6.9 +/- 1.7%) (P < 0.01), but not to either 24-h BP, SVRI or CFR. CONCLUSION: The results show that changes in neither BP nor SVRI reflected changes in minimum vascular resistance. However, changes in the forearm and coronary microcirculation occurred in parallel. Moreover, we demonstrated that neither BP nor SVRI reduction can predict changes in microvascular structure in hypertension. Thus, direct measurements of microvascular structure are needed to determine whether improvement is obtained. PMID- 22306850 TI - Ambulatory blood pressure monitoring and development of cardiovascular events in high-risk patients included in the Spanish ABPM registry: the CARDIORISC Event study. AB - BACKGROUND AND AIM: Ambulatory blood pressure monitoring (ABPM) is superior to conventional BP measurement in predicting outcome, with baseline 24-h, daytime and night-time absolute values, as well as relative nocturnal decline, as powerful determinants of prognosis. We aimed to evaluate ABPM estimates on the appearance of cardiovascular events and mortality in a cohort of high-risk treated hypertensive patients. METHODS AND RESULTS: A total of 2115 treated hypertensive patients with high or very high added risk were evaluated by means of office and 24-h ABPM. Cardiovascular events and mortality were assessed after a median follow-up of 4 years. Two hundred and sixty-eight patients (12.7%) experienced a primary event (nonfatal coronary or cerebrovascular event, heart failure hospitalization or cardiovascular death) and 114 died (45 from cardiovascular causes). In a multiple Cox regression model, and after adjusting for baseline cardiovascular risk and office BP, night-time SBP predicted cardiovascular events [hazard ratio for each SD increase: 1.45; 95% confidence interval (CI) 1.29-1.59]. Values above 130 mmHg increased the risk by 52% in comparison to values less than 115 mmHg. CONCLUSION: In addition to clinical determinants of cardiovascular risk and conventional BP, ABPM performed during treatment adds prognostic significance on the development of cardiovascular events in high-risk hypertensive patients. Among different ABPM-derived values, night-time SBP is the most potent predictor of outcome. PMID- 22306852 TI - Role of endogenous hydrogen sulfide in neurogenic relaxation of rat corpus cavernosum. AB - Relaxation of corpus cavernosum during penile erection is mediated by a non adrenergic non-cholinergic (NANC) neurotransmission and by the endothelium via the release of nitric oxide. Hydrogen sulfide (H(2)S) is an endogenous gaseous mediator which is a potent vasodilator and a neurotransmitter. This study was initiated to characterize the role of H(2)S in NANC neurogenic transmission in rat corpus cavernosum. The expression of H(2)S producing enzymes was assessed using RT-PCR as well as Western blotting and showed the expression of cystathionine gamma-lyase (CSE) in rat corporal tissue. Homogenates from rat corpus cavernosum convert l-cysteine to H(2)S and this was partially inhibited by a CSE inhibitor, propargylglycine. Electrical stimulation of corporal tissue strips caused NANC relaxation. This neurogenic relaxation was significantly enhanced by inhibition of CSE by propargylglycine indicating that endogenously produced H(2)S may have a negative regulatory role in neurogenic relaxation of rat corpus cavernosum. To investigate this further we used physiologically relevant concentrations of exogenous NaHS, and showed that nanomolar concentrations could inhibit corporal relaxation induced by a nitroxyl (HNO) donor (Angeli's salt) but not with nitrosonium (NO(+)) or NO donors. This suggests that an interaction between endogenously produced H(2)S and nitroxyl (HNO) might be involved in erectile function. PMID- 22306853 TI - Severe ALG8-CDG (CDG-Ih) associated with homozygosity for two novel missense mutations detected by exome sequencing of candidate genes. AB - Posttranslationally glycosylated proteins are important in many biological processes in humans and Congenital disorders of glycosylation (CDGs) are associated with a broad range of phenotypes. Type I CDGs are a group of rare autosomal recessive conditions. To date 17 subtypes have been enzymatically and molecularly characterized. Impaired function of the enzyme dolichyl pyrophosphate Glc(1)Man(9)GlcNAc(2) alpha-1,3-glucosyltransferase encoded by the ALG8 gene, causes ALG8-CDG (CDG-Ih, OMIM #608104). This enzyme facilitates the transfer of a second glucose molecule to a growing lipid-linked oligosaccharide chain, a process that transpires in the endoplasmic reticulum (ER). We present a female patient of consanguineous parents, with pre- and postnatal growth retardation, dysmorphic features, significant developmental delay, visual impairment and an electrophoretic serum transferrin pattern indicative of a type I CDG. Type I CDG subgroup was determined by exome sequencing facilitated by homozygosity analysis. The patient was homozygous for two variants, nine nucleotides apart, in exon 8 of ALG8; c.799T > C [p.Ser267Pro] and c.808T > C [p.Phe270Leu]. Both missense mutations are predicted to affect a conserved region of an intraluminal ER loop of dolichyl pyrophosphate Glc(1)Man(9)GlcNAc(2) alpha-1,3-glucosyltransferase. To our knowledge, the current report describes the ninth published case of ALG8-CDG, contributing to the further delineation of this rare and variable disorder. PMID- 22306854 TI - Vaccination with Haemophilus influenzae type b conjugate vaccine reduces bacterial meningitis in Morocco. AB - INTRODUCTION: Haemophilus influenzae type b (Hib) is a leading cause of bacterial meningitis and pneumonia and can be prevented by Hib vaccine. We conducted a vaccine impact evaluation to support continued use of Hib vaccine in Morocco following introduction in 2007. METHODS: Bacterial meningitis surveillance data from 2004 to 2009 were obtained from 11 sentinel hospitals located in eight provinces and one prefecture in Morocco to examine Hi meningitis reporting for cases aged <5 years. We defined the years of 2004-2006 as the pre-vaccine period and 2008-2009 as the post-vaccine period and compared the mean annual number of confirmed Hi meningitis cases for these time periods using a Chi-square test. We calculated the minimum incidence of Hi meningitis during the evaluation period in Grand Casa Prefecture, where the catchment population could be estimated. RESULTS: From 2004 to 2009, 1844 suspected meningitis case-patients aged <5 years were reported; 354 (19.2%) were confirmed with bacterial meningitis, including 105 (29.7%) Hi cases. The mean annual number of confirmed Hi meningitis cases decreased by 75%, from 24 in the pre-vaccine period to 6 during the post-vaccine period (p<0.001). Assuming Hi cases with unknown age were <5 years of age, the estimated minimum incidence of confirmed Hi meningitis in Grand Casa Prefecture decreased by 93%, from 15 cases per 100,000 children in the pre-vaccine period to 1 case per 100,000 children in the post-vaccine period. CONCLUSION: Hib vaccine introduction likely significantly reduced the occurrence of Hi meningitis among children aged <5 years at the 11 sentinel hospitals included in this evaluation in Morocco, suggesting that continued use of Hib vaccine in Morocco would be beneficial. PMID- 22306855 TI - Randomized trial of HPV4 vaccine assessing the response to HPV4 vaccine in two schedules among Peruvian female sex workers. AB - Two hundred female sex workers (FSWs) in Lima, Peru were randomized to receive HPV4 vaccine in the standard (0, 2, 6 months) or a modified schedule (0, 3, 6 months). One hundred and eighty four (92%) participants completed 3 doses of vaccine. Baseline seropositive rates were 58% for HPV6, 22.5% for HPV11, 41.5% for HPV16, and 13% for HPV18. The final geometric mean antibody titer (GMT) following vaccination was significantly greater for women who were seropositive at baseline compared to seronegative women: HPV6 (GMT ratio=2.3, p<0.01), HPV11 (GMT ratio=2.7, p<0.01), HPV16 (GMT ratio=1.3, p=0.04), and HPV18 (GMT ratio=2.4, p<0.01). Antibody titers in the modified schedule were not inferior to those in the standard schedule, suggesting the modified schedule may be paired with required STD visits. Although all women benefit from vaccination, administration at a younger age and before sexual debut is needed to achieve maximum protection from vaccine. PMID- 22306856 TI - Superior immunogenicity of a freeze-dried, cell culture-derived Japanese encephalitis vaccine (inactivated). AB - Japanese encephalitis is an infectious disease caused by the Japanese encephalitis virus, which is widespread throughout Asia. The worldwide incidence is 50,000 cases per year. There is no specific treatment available, but inactivated mouse brain-derived vaccine was used from the 1950s to prevent infection. However, quality control of mouse brain-derived vaccines is difficult, and therefore a new freeze-dried, cell culture-derived Japanese encephalitis vaccine (inactivated) (JEBIK V; development code: BK-VJE) was developed. In this paper, we report an analysis of neutralizing antibody titers in vaccinated subjects enrolled in clinical study of BK-VJE at various doses, and study of BK VJE with the mouse brain-derived vaccine as a control. The results show that BK VJE has superior immunogenicity compared to mouse brain-derived vaccine. PMID- 22306857 TI - Willingness to receive pandemic influenza A (H1N1) vaccine among doctors and nurses in public health facilities in Ibadan, Nigeria. AB - BACKGROUND: As part of global efforts to contain the spread of the 2009 pandemic influenza A (H1N1), the Federal Ministry of Health of Nigeria is embarking on the vaccination of health care workers employed in health facilities nationwide. This study was designed to assess the willingness of doctors and nurses working in public health facilities in Ibadan, Nigeria to receive the influenza A (H1N1) vaccine. METHODS: A descriptive cross-sectional study design was employed. Stratified simple random sampling was used to select a total of 304 doctors and nurses who worked at the public primary (70), secondary (51) and tertiary (183) levels of health care facilities in Ibadan. A self-administered, structured questionnaire that contained items on socio-demographics, sources of information, knowledge about the infection and the vaccine, risk perception, willingness to receive the vaccine and suggestions to improve vaccination acceptance by health care workers was used to collect the data. MAIN FINDINGS: A total of 255 providers responded for an overall response rate of 84%. The mean age of the respondents was 35.0 +/- 9.7 years. A high proportion (88.2%) of the participants, including 94.9% of the doctors and 87.0% of the nurses, reported a willingness to receive the vaccine. Perceptions regarding the risk of contracting influenza, the availability of effective vaccinations for prevention and beliefs that the disease is fatal were reasons given by respondents who reported willingness to receive the vaccination. Those participants who reported ever hearing about the pandemic (AOR 2.0, 95% CI 1.2-3.2) and those who had a high risk perception of contracting the disease (AOR 2.0, 95% CI 1.2-3.7) were likely to receive the vaccine. CONCLUSION: Doctors and nurses at the three levels of health care facilities in Ibadan were willing to receive the pandemic influenza A (H1N1) vaccine. Efforts should be made to deliver the vaccines via adequate planning. PMID- 22306858 TI - Vaccination with coxsackievirus B3 virus-like particles elicits humoral immune response and protects mice against myocarditis. AB - Coxsackievirus B3 (CVB3), along with other enteroviruses, is involved in about 50% of myocarditis cases and in the pathogenesis of dilated cardiomyopathy. Prevention of CVB3 infection is therefore highly desirable. Virus-like particles (VLPs) are structurally similar to native virus particles and therefore are far better immunogens than any other subunit vaccines. Recombinant baculoviruses carrying either the intact, entire coding region of CVB3 or the four individual coding regions for virus proteins 1-4 (VP1-4) were constructed. Expression of CVB3 capsid proteins in insect cells infected with recombinant baculovirus was detected by immunofluorescence and Western blot analysis. Sucrose gradient ultracentrifugation fractions of the infected cell lysates contained peaks of CVB3 antigen with an approximate density of 1.14g/ml. Electron microscopy demonstrated the presence of VLP in these sucrose fractions. The CVB3 VLP was non infectious in tissue culture. SWR (H-2(q)) mice vaccinated with CVB3 VLP developed antibodies to CVB3 capsid proteins after the first boost. Antibody titre was comparable to the level induced by an attenuated CVB3 vaccine. Vaccinated animals were protected from myocarditis when subsequently challenged with cardiovirulent CVB3 (chimera-2). Vaccination with VLP produced from the complete CVB3 coding region gave a greater immune response and afforded better protection than with VLP from the quadruple expression vector. These results demonstrate that CVB3 capsid proteins expressed in insect cells have the intrinsic capacity to assemble into non-infectious VLP, which afforded protection from CVB3 infection to mice when used as a vaccine. PMID- 22306859 TI - Cross protection of a Mannheimia haemolytica A1 Lkt-/Pasteurella multocida DeltahyaE bovine respiratory disease vaccine against experimental challenge with Mannheimia haemolytica A6 in calves. AB - Bovine respiratory disease causes significant economic losses in both beef and dairy calf industries. Although multi-factorial in nature, the disease is characterized by an acute fibrinous lobar pneumonia typically associated with the isolation of Mannheimia haemolytica. M. haemolytica A1 and A6 are the two most commonly isolated serotypes from cattle, however, the majority of vaccines have not demonstrated cross-serotype protection. In the current study, the efficacy of a novel, attenuated live vaccine, containing both M. haemolytica serotype A1 and Pasteurella multocida, was evaluated in calves challenged with M. haemolytica serotype A6. Although the challenge was more severe than expected, vaccinated calves had reduced clinical scores, lower mortality, and significantly lower lung lesion scores compared to the placebo-vaccinated control group. The results demonstrate that vaccination with an attenuated live vaccine containing M. haemolytica serotype A1 can protect calves against clinical disease following challenge with M. haemolytica serotype A6. PMID- 22306860 TI - Meniere's disease might be an autoimmune condition? AB - OBJECTIVES: To review our current knowledge of the pathogenesis of Meniere's disease, including viral infection and immune system-mediated mechanisms, and to discuss the pathogenesis as it relates to pharmacotherapy. SYSTEMATIC REVIEW METHODOLOGY: Relevant publications on the aetiopathogenesis, molecular biology, genetics and histopathology of Meniere's disease from 1861 to 2011 were analysed. RESULTS AND CONCLUSIONS: Meniere's disease is characterised by intermittent episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural pressure. The aetiology and pathogenesis remain unknown. Proposed theories of causation include viral infections and immune system-mediated mechanisms. The immune response in Meniere's disease is focused on inner ear antigens. Approximately one-third of Meniere's disease cases seem to be of an autoimmune origin although the immunological mechanisms involved are not clear. The diagnosis of autoimmune inner ear disease is based either on clinical criteria or on a positive response to steroids. The antiviral approach has virtually eliminated the use of various surgical methods used in the past. Steroid responsiveness is high, and with prompt treatment, inner ear damage may be reversible. The administration of etanercept improves or stabilises symptoms in treated patients. Treatment of antiphospholipid syndrome can be directed toward preventing thromboembolic events by using antithrombotic medications. Only warfarin has been shown to be effective. Gene therapy can be used to transfer genetic material into inner ear cells using viral vectors and to protect, rescue, and even regenerate hair cells of the inner ear. PMID- 22306861 TI - Laboratory experiment on the determination of radiostrontium transfer parameter in water - fish compartment system. AB - A laboratory experiment was conducted to investigate the water - fish transfer parameter of radiostrontium that potentially contaminate human body through water - fish - human pathway in the nuclear accident cases. In this experiment, carp fish (Cyprinus carpio), generally produced and consumed by Indonesian people, were cultured in a tank filled with 500 L water contaminated with (85)Sr for two months. The observation of fish growth and radioactivity were conducted every five days by taking up three fish and water samples. The fish were dissected and separated into muscle, bones and internally organ, then destructed using chloric acid. The fish and water samples were then measured using gamma spectrometer with HPGe detector. The transfer parameter of transfer factor (T(f)), uptake rate constant (u), elimination rate constant (k), and the effective half life (T(e)) were analyzed by mathematical equations. The high (85)Sr concentration was observed in the bone by the T(f) value of 67.99 +/- 9.68 mL g(-1) wet weight, whereas the concentration in muscle and internal organ were lower with the T(f) of 26.05 +/- 4.44 mL g(-1) wet weight and 16.95 +/- 2.34 mL g(-1) wet weight, respectively. The values of u obtained from the mathematical calculation were 0.025 day(-1), 0.029 day(-1), and 0.04 day(-1) for bone, muscle, and internal organ, respectively. Those values were higher compared to the k values, i.e. 0.018 day(-1), 0.025 day(-1), and 0.022 day(-1) indicating the accumulation were take place in bone, muscle, and internal organ. The effective half life, which is the sum of physical and biological half life, of (85)Sr in carp was about 30 days. The transfer parameter values determined from this experiment can be used in internal radiation doses assessment through water - fish - human pathways in case of radiostrontium contamination in freshwater environment, so a recommendation can be considered relating to the fish consumption during or after radiostrontium release to the environment. PMID- 22306862 TI - Recent advances in the risk assessment of melamine and cyanuric acid in animal feed. AB - Melamine can be present at low levels in food and feed mostly from its legal use as a food contact material in laminates and plastics, as a trace contaminant in nitrogen supplements used in animal feeds, and as a metabolite of the pesticide cyromazine. The mechanism of toxicity of melamine involves dose-dependent formation of crystals with either endogenous uric acid or a structural analogue of melamine, cyanuric acid, in renal tubules resulting in potential acute kidney failure. Co-exposure to melamine and cyanuric acid in livestock, fish, pets and laboratory animals shows higher toxicity compared with melamine or cyanuric acid alone. Evidence for crystal formation between melamine and other structural analogs i.e. ammelide and ammeline is limited. Illegal pet food adulterations with melamine and cyanuric acid and adulteration of milk with melamine resulted in melamine-cyanuric acid crystals, kidney damage and deaths of cats and dogs and melamine-uric acid stones, hospitalisation and deaths of children in China respectively. Following these incidents, the tolerable daily intake for melamine was re-evaluated by the U.S. Food and Drug Administration, the World Health Organisation, and the Scientific Panel on Contaminants in the Food Chain of the European Food Safety Authority (EFSA). This review provides an overview of toxicology, the adulteration incidents and risk assessments for melamine and its structural analogues. Particular focus is given to the recent EFSA risk assessment addressing impacts on animal and human health of background levels of melamine and structural analogues in animal feed. Recent research and future directions are discussed. PMID- 22306863 TI - SPARC prevents maturation of cholinergic presynaptic terminals. AB - Secreted Protein Acidic and Rich in Cysteine (SPARC) is a matricellular protein produced by glial cells. Although it is highly expressed in synaptogenic areas in the developing nervous system, it is still unclear whether this molecule displays an action on synaptic activity. We show that nanomolar concentrations of SPARC favour a more efficient synapse formation and increase short term depression in single cell cholinergic microcultures. The change in synaptic plasticity, which is also observed when SPARC is locally secreted on stable synapses for 24-48 h, is caused by a high release probability and a reduction in the size of the rapidly releasable pool of vesicles. Both features are attributable to synapses operating at an immature stage as demonstrated by correlative electrophysiology and electron microscopy experiments. Presynaptic terminals developed in the presence of SPARC display few cytoplasmic vesicles and two to threefold decrease in the number of docked vesicles at active zones. At the postsynaptic level, the analysis of miniature excitatory postsynaptic currents suggests SPARC has little effect on the number of nicotinic receptors but might alter their composition. The widespread distribution of SPARC makes current findings potentially relevant to other excitatory synapses and development of neuronal circuits. PMID- 22306864 TI - Drebrin controls neuronal migration through the formation and alignment of the leading process. AB - Formation of a functional nervous system requires neurons to migrate to the correct place within the developing brain. Tangentially migrating neurons are guided by a leading process which extends towards the target and is followed by the cell body. How environmental cues are coupled to specific cytoskeletal changes to produce and guide leading process growth is unknown. One such cytoskeletal modulator is drebrin, an actin-binding protein known to induce protrusions in many cell types and be important for regulating neuronal morphology. Using the migration of oculomotor neurons as a model, we have shown that drebrin is necessary for the generation and guidance of the leading process. In the absence of drebrin, leading processes are not formed and cells fail to migrate although axon growth and pathfinding appear grossly unaffected. Conversely, when levels of drebrin are elevated the leading processes turn away from their target and as a result the motor neuron cell bodies move along abnormal paths within the brain. The aberrant trajectories were highly reproducible suggesting that drebrin is required to interpret specific guidance cues. The axons and growth cones of these neurons display morphological changes, particularly increased branching and filopodial number but despite this they extend along normal developmental pathways. Collectively these results show that drebrin is initially necessary for the formation of a leading process and subsequently for this to respond to navigational signals and grow in the correct direction. Furthermore, we have shown that the actions of drebrin can be segregated within individual motor neurons to direct their migration independently of axon guidance. PMID- 22306865 TI - Alterations of the amplitude of low-frequency fluctuations in treatment-resistant and treatment-response depression: a resting-state fMRI study. AB - BACKGROUND: Patients with treatment-resistant depression (TRD) and those with treatment-response depression (TSD) respond to antidepressants differently and previous studies have commonly reported different brain networks in resistant and nonresistant patients. Using the amplitude of low-frequency fluctuations (ALFF) approach, we explored ALFF values of the brain regions in TRD and TSD patients at resting state to test the hypothesis of the different brain networks in TRD and TSD patients. METHODS: Eighteen TRD patients, 17 TSD patients and 17 gender-, age , and education-matched healthy subjects participated in the resting-state fMRI scans. RESULTS: There are widespread differences in ALFF values among TRD patients, TSD patients and healthy subjects throughout the cerebellum, the visual recognition circuit (middle temporal gyrus, middle/inferior occipital gyrus and fusiform), the hate circuit (putamen), the default circuit (ACC and medial frontal gyrus) and the risk/action circuit (inferior frontal gyrus). The differences in brain circuits between the TRD and TSD patients are mainly in the cerebellum, the visual recognition circuit and the default circuit. CONCLUSIONS: The affected brain circuits of TRD patients might be partly different from those of TSD patients. PMID- 22306866 TI - In celebration of Sydney M. Finegold, M.D.: bacteroides fragilis in the colon: the good & the bad. AB - Dr. Sydney Finegold is one of the most heralded leaders in the discovery, classification and scientific knowledge of anaerobic bacteria. On this occasion of his 90th birthday, this paper celebrates his lifetime of accomplishments and provides a perspective on the changes and growth in our understanding of one anaerobic species, Bacteroides fragilis. Over the last nearly 40 years, clinical and research data have fostered our current view that B. fragilis are essential symbiotes as well as, in some circumstances, pathogens with the capacity to induce both acute systemic and abdominal illnesses and possibly chronic colonic diseases. PMID- 22306867 TI - beta-Rhamnosides from 6-thio mannosides. AB - Upon condensation of 6-thio-6-deoxy-mannosyl donors 1,2-cis products are obtained with a high degree of stereoselectivity. Subsequent reductive removal of the 6 thio functionality gives 1,2-cis rhamnosides. The 1,2-cis-selectivity can be rationalized with a product forming (3)H(4)-oxocarbenium, which is in equilibrium with a bridged sulfonium intermediate. PMID- 22306868 TI - [Molecular mechanisms and functions of autophagy and the ubiquitin-proteasome pathway]. AB - All proteins in eukaryotic cells are continually being degraded and replaced. Autophagy and the ubiquitin-proteasome system are two mechanisms for intracellular protein degradation. Autophagy is mediated by lysosome, and is further divided into chaperone-mediated autophagy, microautophagy and macroautophagy. The ubiquitin-proteasome system is highly complex and mediated by ubiquitin, which participates in intracellular protein degradation in a specific manner. It is now known that degradation of intracellular proteins is involved in regulation of a series of cellular processes, including cell-cycle division, DNA repair, cell growth and differentiation, quality control, pathogen infection, and apoptosis. The aberrations in the protein degradation systems are involved in many serious human diseases. The present review summarizes the mechanisms of protein degradation and related human diseases. PMID- 22306869 TI - [Telomere biology of the chicken]. AB - Telomeres, the nucleoprotein "caps" protecting the ends of linear chromosomes, are maintained by telomerase. Telomeres have important roles in maintaining genomic stability and preventing senescence or oncogenesis. Chicken is a classical model animal for genetic and developmental studies. With further development of chicken genomics, great progress has been made in research of chicken telomere and telomerase. This review describes recent advances and future research directions in chicken telomere biology. PMID- 22306870 TI - [Relationship of epidermal growth factor receptor in lung development]. AB - The epidermal growth factor receptor (EGFR), a transmembrane protein receptor, is a member of ErbB family with signal-transducing tyrosine kinase activity. After combined with the ligand, EGFR homologous or heterologous dimers are formed to induce intracellular signal transduction, activate downstream signal transduction pathways, and then produce a series of biological effects. RAF/MEK/RAS/ERK pathway is relevant to cell proliferation, differentiation and apoptosis; while PDK1/AKT /PI3K pathway is involved in cell migration and adhesion. EGFR can promote the maturity of pulmonary type II epithelial cells and the synthesis and secretion of pulmonary surfactant. EGFR shows the effect on mammal lungs in a time-space and dose-dependent manner. The down-regulated expression of it will lead to immature lung development, while the over-expression can promote the cell proliferation, invasion and metastasis of the lung cancer cells. This paper reviewed advances in the study for EGFR and its signal pathway, as well as the relationship among EGFR, atelectasis and lung cancer. PMID- 22306871 TI - [Bacterial quorum sensing in an evolutionary perspective]. AB - In contrast to the individual and nonsocial organism view of bacteria, recent discoveries show that bacteria can communicate and exhibit population behaviour via a system known as quorum sensing. Some bacterial behaviour can only be initiated when the cell number reaches a certain level (Quorum sensing, QS). It is generally believed that quorum sensing is used to coordinate cooperative behaviours at the population level; however, many issues exist regarding the evolution or development of such a system. In the present paper, the evolutionary process of bacterial quorum-sensing systems is discussed based on recent events and progresses in this field. As quorum sensing systems are often affected by environ-mental factors, such as temperature, pH, and nutrient levels, it is hence proposed that the evolution of bacterial cooperation, such as the quorum sensing, is rather a dynamic and ever-changing process which is radically affected by environmental conditions, genetic exchanges, as well as by changes in microbial community. The dynamic transformation suggests the advantages of cheaters of the system might have been short-lasted and confined in certain conditions and diminish over a long run. PMID- 22306872 TI - [The small RNAs in plant immunity]. AB - Small RNAs are involved in a multitude of biological processes in plants. Based on their origins and precursor structures, small RNAs can be divided into two major classes: microRNAs (miRNAs) and small interference RNAs (siRNAs). Small RNAs are typically 21-24 nucleotide (nt) long, and differ in both biogenesis and biological function. In the pathogenic process, pathogens can either induce or suppress the synthesis of small RNAs, which, in turn, regulate the expression of pathogenesis-related genes to mediate diverse plant-pathogen interactions. The biogenesis and biological functions of small RNAs, together with possible regulation mechanisms underlying the host-pathogen interactions, are summarized in this review. PMID- 22306873 TI - [Chinese Holstein Cattle effective population size estimated from whole genome linkage disequilibrium]. AB - Effective populations size (Ne) is an important population parameter that helps to explain genetic variation, population evolution and understanding of the genetic architecture underlying complex traits. With the availability of high dense SNP panels, more and more researches focus on estimating of Ne using linkage disequilibrium (LD) between SNPs. In this study, we estimated the effective population size from 2093 Chinese Holstein Cattle genotyped with Illumina BovineSNP50 BeadChip. After removal of individual with call rate lt; 95%, SNPs with call rate lt; 95%, minor allele frequency lt; 5% and Hardy Weinberg Equilibrium test with Plt;0.0001, 1 968 individuals with 38 796 SNPs were remained. Eight kinds of SNP pairs with the distances 0.1, 0.2, 0.5, 1, 2, 5, 10, and 15 Mb were respectively chosen to estimate the effective population size of Chinese Holstein cattle from 4 generations ago. It is demonstrated from the results of this study that the effective population size of Chinese Holstein is decreased in the past generations, and the corresponding effective population size at ~4 generations ago is only around 45. PMID- 22306874 TI - [Identification and evolutionary analysis of the Xenopus tropicalis bHLH transcription factors]. AB - Xenopus is an important model animal for biomedicine researches. In order to probe into the classification and function of the basic helix-loop-helix (bHLH) transcription factor family, we conducted a genome-wide survey and identified 70 bHLH transcription factors using the Xenopus tropicalis genome project data in the study. Among these transcription factors, 69 bHLH transcription factors were classified into 6 large groups composed of 34 sub-families and the remaining one was classified as 'orphan'. Results of Gene Ontology (GO) enrichment statistics showed 51 frequent GO annotation categories. Statistical analysis of the GO annotations showed that these 70 bHLH proteins tended to be frequently related to transcription regulator activity, regulation of transcription, DNA binding, regulation of RNA metabolic process, DNA-dependent regulation of transcription, transcription, and transcription factor activity, indicating that they were expected to be the most common GO categories of transcriptional factors. Moreover, a number of bHLH genes were revealed to play important regulation roles in special development and physiological processes, such as muscle tissue and organ (striated muscle, skeletal muscle, eye muscle, and pharyngeal muscle) differentiation and development, e.g., digestive system development, pharynx development and sensory organ development, regulation of nucleobase, nucleoside and nucleotide and nucleic acid metabolic process, regulation of biosynthetic process, DNA binding, and protein heterodimerization activity, etc. There were also some important signaling pathways in the significant GO categories. We made the evolutionary analysis of Hes transcription factor family as well. This preliminary result lays a solid foundation for further re-searches on X. tropicalis. PMID- 22306875 TI - [Polymorphism of MSTN gene and its association with growth traits in yellow catfish (Pelteobagruse fulvidraco)]. AB - Myostatin (MSTN) gene has negative influence on the growth of muscle, which belongs to transforming growth factor-beta family. Using single-strand conformation polymorphism (SSCP), single nucleotide polymorphisms (SNPs) of MSTN gene were detected in yellow catfish. Correlation analysis between MSTN polymorphisms and growth traits was also carried out. Results indicated that five genotypes (AA, BB, CC, CD and DD) were found in the first intron with one deletion site and two mutant sites (T1003del, G1022A and T1063G), two genotypes (EE and EF) were found in the third exon with one mutant site (T132C). The individuals with genotypes AA had a lager value than the individuals with the genotype CD and DD in total length, body length, body height, body width, head length and body weight (Plt;0.05). The female individuals with genotypes AA also had a lager value than the female individuals with genotypes DD in total length, body length, body height, body width, caudal peduncle height, caudal peduncle width and body weight (Plt;0.05). This implies that genotype AA has a positive influence on the growth traits of female yellow catfish, and genotype DD is opposite. Genotypes AA and DD can be used in marker assisted selection of female yellow catfish breeding in the future. PMID- 22306876 TI - [Characterisation of a rice dwarf and twist leaf 1 (dtl1) mutant and fine mapping of DTL1 gene]. AB - Plant height is one of the most important agronomic traits, which determines grain yield. By a largescale screening of our mutant population, we identified a dwarf with twisty leaf mutant (dwarf and twist leaf 1, dtl1). Besides dwarf with twisty leaf, dtl1 also showed reduced tiller number and sterile phenotypes. Based on the internode length of dtl1, this mutant belongs to the nl type of dwarfing phenotype. Physiological assay with two phytohormones, gibberellin (GA), and brassinosteroid (BR), suggested that dtl1 was neither deficient nor insensitive to GA and BR. Genetic analysis showed that the phenotype of dtl1 was controlled by a single recessive gene. Using F2 population derived from a cross between dtl1 and an indica cultivar Taichung Native 1, the DTL1 gene was narrowed down to a 70.4 kb between two SSR markers, RM25923 and RM6673, on the long arm of chromosome 10, and co-segregated with InDel marker Z10-29, where thirteen open reading frames were predicted without known gene involved in controlling plant height. Thus, the DTL1 gene might be a novel gene which is related to plant height in rice. PMID- 22306877 TI - [Analysis of genetic variation in rice paddy landraces across 30 years as revealed by microsatellite DNA markers]. AB - To reveal the genetic variation of rice paddy landraces across 30 years, we compared the genetic variation of between 6 paddy rice landraces grown in Yuanyang Hani's terraced fields in Yuanyang County, Yunnan Province in the 1970s (past-grown landraces) and 6 paired ones that have been grown during the past decade (current-grown landraces) using 60 SSR markers. The results showed that one to four alleles were amplified in 60 loci and 159 alleles in all the landraces tested. The number of alleles from the current-grown landraces decreased by 7 alleles compared to the past-grown landraces. The average number of alleles (Na), effective number of alleles (Ne), locus polymorphism information content (PIC), and genotype diversity (H') of the past-grown landraces were higher than those of the current-grown landraces, with Na of 2.567>2.450, Ne of 2.052>1.968, PIC of 0.469>0.439, and H' of 0.768>0.722. The average genetic similarity coefficient (GS) of the past-grown landraces was 0.437 with a range from 0.200 to 0.700 based on the 60 SSR markers, and the average GS of the current-grown landraces was 0.473 with a range from 0.117 to 0.667. In conclusion, the genetic diversity in current-grown landraces was decreased compared to the past-grown landraces, and the degree of variation in some of the allele locus varied in different rice landraces as a result of 30 years' natural and artificial selection. PMID- 22306878 TI - [Cloning and expression analysis of Cu/ZnSOD gene from Galega orientalis L]. AB - SOD is an important enzyme which exists in eukaryote extensively and plays an essential role in stress-tolerance of higher plants. A cDNA of Cu/ZnSOD gene was cloned from Galega orientalis L. using rapid amplification of cDNA ends (RACE) method. The full-length of cDNA sequence is 935 bp, included a 600 bp open reading frame which encoded a 199-amino-acid polypeptide. The molecular weight of this protein was 20.35 kDa. The results of Real-Time PCR indicated that the expression level of Cu/ZnSOD gene was the highest in leaves, moderate in stems, and the least in roots. The expression of Cu/ZnSOD gene under stress of NaCl and PEG was up-regulated firstly and then declined. The expression level was significantly lower than the control after 24 h treated with NaCl. Abscisic acid downregulated the expression of Cu/ZnSOD gene. The result of subcellular localization indicated that Cu/ZnSOD was located in chloroplast. Gene Cu/ZnSOD mainly expressed in the green organs of G. orientalis and played a certain role in resisting osmotic stress. PMID- 22306879 TI - [Transcriptome analysis of early interaction between rice and Magnaporthe oryzae using next-generation sequencing technology]. AB - Magnaporthe oryzae is speculated to express and translocate a set of effector proteins to interfere with rice innate immunity and to promote its invasion. In this study, we carried out a transcriptome analysis of early interaction between rice and M. oryzae using a next generation sequencing technology to identify putative effector protein genes. We totally obtained 338 942 M. oryzae derived sequence tags from around 12.5 M gross mixed tags by referring the genome sequence of reference strain 70-15. These M. oryzae sequences were finally mapped to 779 predicted genes. Of these 799 genes, 108 were predicted to be involved in the interaction between rice and M. oryzae and 42 encoded proteins predicted to be secreted. Expression of these 42 putative secreted protein genes were further assessed using a reverse transcription polymerase chain reaction (RT-PCR) method, which revealed that 12 of them were expressed during the infection. Four of these 12 expressed genes were further confirmed to be expressed specifically during the infection. This study demonstrated an attempt to isolate M. oryzae genes, especially those putative effector protein genes, which are expressed specifically at the early interaction stage using a next-generation sequencing technology. PMID- 22306880 TI - [The effects of SV40 PolyA sequence and its AATAAA signal on upstream GFP gene expression and transcription termination]. AB - SV40 PolyA (Simian virus 40 PolyA, also called PolyA) sequence is DNA sequence (240 bp) that possesses the activity of transcription termination and can add PolyA tail to mRNA. PolyA contains AATAAA hexanucleotide polyadenylation signal. Fourteen copies of Alu in sense orientation (Alu14) were inserted downstream of GFP in pEGFP-C1 to construct pAlu14 plasmid, and then HeLa cells were transiently transfected with pAlu14. Northern blot and fluorescence microscope were used to observe GFP RNA and protein expressions. Our results found that Alu tandem sequence inhibited remarkably GFP gene expression, but produced higher-molecular mass GFP fusion RNA. PolyA and its sequence that was deleted AATAAA signal in sense or antisense orientation were inserted between GFP and Alu tandem sequence in pAlu14. The results showed that all the inserted PolyA sequences partly eliminated the inhibition induced by Alu14. PolyA sequences without AATAAA signal in sense or antisense orientation still induced transcription termination. Antisense PolyA (PolyAas) was divided into four fragments that all are 60 bp long and the middle two fragments were named 2F2R and 3F3R. 2F2R or 3F3R was inserted upstream of Alu tandem sequence in pAlu14. The molecular mass of GFP fusion RNA increased when the copy number of 2F2R increased. 2F2R can support transcription elongation when 2F2R is located upstream of other 2F2R. Nevertheless, 2F2R located upstream of Alu tandem sequence can induce transcription termination. Inserting one copy or 64 copies of 3F3R in upstream of Alu tandem sequence caused the production of lower-molecular-mass GFP RNA. PMID- 22306881 TI - [Analysis of several key problems about the two linkage gene mapping of Neurospora crassa in genetics teaching]. AB - Ordered tetrad analysis is important content in the genetics teaching. In particular, the two linkage gene mapping is not only a key point, but also a difficult one. How to explain the content better is a hard nut for the many genetics teachers or editors of the teaching material to crack. Here, based on teaching practice of many years we summarized several key problems, which are difficult to understand by students and frequently neglected by the teachers and the editors of genetics. Furthermore, we deeply analyzed these problems and presented some opinions and suggestions relative to them so as to provide a reference for the teachers of genetics and the editors of teaching materials. PMID- 22306882 TI - Design and implementation of an Internet based effective controlling and monitoring system with wireless fieldbus communications technologies for process automation--an experimental study. AB - The network requirements of control systems in industrial applications increase day by day. The Internet based control system and various fieldbus systems have been designed in order to meet these requirements. This paper describes an Internet based control system with wireless fieldbus communication designed for distributed processes. The system was implemented as an experimental setup in a laboratory. In industrial facilities, the process control layer and the distance connection of the distributed control devices in the lowest levels of the industrial production environment are provided with fieldbus networks. In this paper, the Internet based control system that will be able to meet the system requirements with a new-generation communication structure, which is called wired/wireless hybrid system, has been designed on field level and carried out to cover all sectors of distributed automation, from process control, to distributed input/output (I/O). The system has been accomplished by hardware structure with a programmable logic controller (PLC), a communication processor (CP) module, two industrial wireless modules and a distributed I/O module, Motor Protection Package (MPP) and software structure with WinCC flexible program used for the screen of Scada (Supervisory Control And Data Acquisition), SIMATIC MANAGER package program ("STEP7") used for the hardware and network configuration and also for downloading control program to PLC. PMID- 22306883 TI - High Throughput, Label-free Screening Small Molecule Compound Libraries for Protein-Ligands using Combination of Small Molecule Microarrays and a Special Ellipsometry-based Optical Scanner. AB - Small-molecule compounds remain the major source of therapeutic and preventative drugs. Developing new drugs against a protein target often requires screening large collections of compounds with diverse structures for ligands or ligand fragments that exhibit sufficiently affinity and desirable inhibition effect on the target before further optimization and development. Since the number of small molecule compounds is large, high-throughput screening (HTS) methods are needed. Small-molecule microarrays (SMM) on a solid support in combination with a suitable binding assay form a viable HTS platform. We demonstrate that by combining an oblique-incidence reflectivity difference optical scanner with SMM we can screen 10,000 small-molecule compounds on a single glass slide for protein ligands without fluorescence labeling. Furthermore using such a label-free assay platform we can simultaneously acquire binding curves of a solution-phase protein to over 10,000 immobilized compounds, thus enabling full characterization of protein-ligand interactions over a wide range of affinity constants. PMID- 22306884 TI - Elevated vitamin B12 levels in autoimmune lymphoproliferative syndrome attributable to elevated haptocorrin in lymphocytes. AB - OBJECTIVE: Identify the etiology of elevated B(12) in autoimmune lymphoproliferative syndrome (ALPS). DESIGN: Peripheral blood of ALPS patients with elevated B(12) and controls were evaluated. RESULTS: Total and holo haptocorrin (HC) levels were 26- and 23-fold higher in ALPS patients, respectively. No abnormal B(12)-binding proteins were found. Western blot revealed HC in lymphocyte lysates only from ALPS patients. CONCLUSION: Elevated concentrations of B(12) found in ALPS patients were due to increased lymphocyte expression of HC. PMID- 22306885 TI - Safety evaluation of stem cells used for clinical cell therapy in chronic liver diseases; with emphasize on biochemical markers. AB - There are several issues to be considered to reduce the risk of rejection and minimize side effects associated with liver cell transplantation in chronic liver diseases. The source and the condition of stem cell proliferation and differentiation ex vivo and the transplantation protocols are important safety considerations for cell based therapy. The biochemical and molecular markers are important tools for safety evaluation of different processes of cell expansion and transplantation. Studies show that hepatocytes differentiated from adult and embryonic stem cells exhibit biochemical and metabolic properties resembling mature hepatocytes. Therefore these assays can help to assess the biological and metabolic performance of hepatocytes and progenitor stem cells. The assays also help in testing the contribution of transplanted hepatocytes in improving the repair and function of damaged liver in the recipient. Here we review the biochemical and metabolic markers, which are implicated in evaluation of safety issues of stem cells used for therapeutic purposes in chronic liver diseases and regeneration of damaged liver. We also highlight application of biochemical tests for assessment of liver cell transplantation. PMID- 22306886 TI - Altered expression of talin 1 in peripheral immune cells points to a significant role of the innate immune system in spontaneous autoimmune uveitis. AB - The molecular mechanism which enables activated immune cells to cross the blood retinal barrier in spontaneous autoimmune uveitis is yet to be unraveled. Equine recurrent uveitis is the only spontaneous animal model allowing us to investigate the autoimmune mediated transformation of leukocytes in the course of this sight threatening disease. Hypothesizing that peripheral blood immune cells change their protein expression pattern in spontaneous autoimmune uveitis, we used DIGE to detect proteins with altered abundance comparing peripheral immune cells of healthy and ERU diseased horses. Among others, we found a significant downregulation of talin 1 in peripheral blood granulocytes of ERU specimen, pointing to changes in beta integrin activation and indicating a significant role of the innate immune system in spontaneous autoimmune diseases. PMID- 22306887 TI - Polarity selectivity of spatial interactions in perceived contrast. AB - The apparent contrast of a texture is reduced when surrounded by another texture with high contrast. This contrast-contrast phenomenon has been thought to be a result of spatial interactions between visual channels that encode contrast energy. In the present study, we show that contrast-contrast is selective to luminance polarity by using texture patterns composed of sparse elongated blobs. The apparent contrast of a texture of bright (dark) elements was substantially reduced only when it was surrounded by a texture of elements with the same polarity. This polarity specificity was not evident for textures with high element densities, which were similar to those used in previous studies, probably because such stimuli should inevitably activate both on- and off-type sensors. We also found that polarity-selective suppression decreased as the difference in orientation between the center and surround elements increased but remained for orthogonally oriented elements. These results suggest that the contrast-contrast illusion largely depends on spatial interactions between visual channels that are selective to on-off polarity and only weakly selective to orientation. PMID- 22306888 TI - When viewing natural scenes, do abnormal colors impact on spatial or temporal parameters of eye movements? AB - Since Treisman's theory, it has been generally accepted that color is an elementary feature that guides eye movements when looking at natural scenes. Hence, most computational models of visual attention predict eye movements using color as an important visual feature. In this paper, using experimental data, we show that color does not affect where observers look when viewing natural scene images. Neither colors nor abnormal colors modify observers' fixation locations when compared to the same scenes in grayscale. In the same way, we did not find any significant difference between the scanpaths under grayscale, color, or abnormal color viewing conditions. However, we observed a decrease in fixation duration for color and abnormal color, and this was particularly true at the beginning of scene exploration. Finally, we found that abnormal color modifies saccade amplitude distribution. PMID- 22306889 TI - A triple dissociation between learning of target, distractors, and spatial contexts. AB - When we perform any task, we engage a diverse set of processes. These processes can be optimized with learning. While there exists substantial research that probes specific aspects of learning, there is a scarcity of research regarding interactions between different types of learning. Here, we investigate possible interactions between Perceptual Learning (PL) and Contextual Learning (CL), two types of implicit learning that have garnered much attention in the psychological sciences and that often co-occur in natural settings. PL increases sensitivity to features of task targets and distractors and is thought to involve improvements in low-level perceptual processing. CL regards learning of regularities in the environment (such as spatial relations between objects) and is consistent with improvements in higher level perceptual processes. Surprisingly, we found CL, PL for target features, and PL for distractor features to be independent. This triple dissociation demonstrates how different learning processes may operate in parallel as tasks are mastered. PMID- 22306890 TI - Memorization and recall of very long lists accounted for within the Long-Term Working Memory framework. AB - In a recent paper, Hu, Ericsson, Yang, and Lu (2009) found that an ability to memorize very long lists of digits is not mediated by the same mechanisms as exceptional memory for rapidly presented lists, which has been the traditional focus of laboratory research. Chao Lu is the holder of the Guinness World Record for reciting the most decimal positions of pi, yet he lacks an exceptional memory span for digits. In the first part of this paper we analyzed the reliability and structure of his reported encodings for lists of 300 digits and his application of the story mnemonic. Next, his study and recall times for lists of digits were analyzed to test hypotheses about his detailed encoding processes, and cued recall performance was used to assess the structure of his encodings. Three experiments were then designed to interfere with the uniqueness of Chao Lu's story encodings, and evidence was found for his remarkable ability to adapt his encoding processes to reduce the interference. Finally, we show how his skills for encoding and recalling long lists can be accounted for within the theoretical framework of Ericsson and Kintsch's (1995) Long-Term Working Memory. PMID- 22306891 TI - The complexity of public engagement. PMID- 22306893 TI - Nanopores: Tiny holes with great promise. PMID- 22306894 TI - Thermal materials: Pulling together to control heat flow. PMID- 22306895 TI - Nanoelectronics: Ferroelectric devices show potential. PMID- 22306896 TI - Topological insulators: The surface surfaces. PMID- 22306898 TI - Myeloid-derived suppressor cells in cancer patients: a clinical perspective. AB - Myeloid-derived suppressor cells (MDSCs) represent a heterogenous collection of immature myeloid cells endowed with suppressive function on the immune response. Their presence has been extensively investigated in preclinical models, especially in the context of cancer. One of the major obstacles in their accurate identification has been the definition of an unambiguous phenotype, shared between mice and humans, and clearly correlating with their suppressive function. In this paper, we review the literature concerning the phenotype in mouse and in humans, showing that at least 2 subsets of MDSCs are present under different situations. We also address the role of MDSCs in tumor progression, evaluate the prognostic significance of MDSC in cancer patients, and their possible role as marker of clinical outcome and response to therapy. Finally, we examine the strategies designed to modulate MDSCs in cancer patients, which might represent an innovative approach to enhance the effectiveness of immune-based therapies. PMID- 22306899 TI - Improving T-cell immunotherapy for melanoma through a mathematically motivated strategy: efficacy in numbers? AB - T-cell mediated immunotherapy for malignant diseases has become an effective treatment option, especially in malignant melanoma. Recent advances have enabled the transfer of high T-cell numbers with high functionality. However, with more T cells becoming technically available for transfer, questions about dose, treatment schedule, and safety become most relevant. Mathematical oncology can simulate tumor characteristics in silico and predict the tumor response to novel therapeutics. Using similar methods to classical pharmacokinetics/pharmacodynamics-type models, mathematical oncology translates the findings into a multiparameter model system and simulates T-cell therapy for malignant diseases. The tumor and immune system dynamics model can provide minimal requirements (in terms of T-cell dose and T-cell functionality) depending on the tumor characteristics (growth rate, residual tumor size) for a clinical study, and help select the best treatment schedule (repetitive doses, minimally required duration, etc.). Here, we present a new mathematical model developed for modeling cellular immunotherapy for melanoma. Computer simulations based on the new model offer an explanation for the observed finding from clinical trials that the patients with the smallest tumor load respond better. We simulate different parameters critical for improvement of cellular therapy for patients with high tumor load of fast-growing tumors. We show that tumor growth rate and tumor load are crucial in predicting the outcome of T-cell therapy. Rather than intuitively extrapolating from experimental data, we demonstrate how mathematical oncology can assist in rational planning of clinical trials. PMID- 22306900 TI - Tumor protection by IL-7 secreting whole cell vaccine is merely mediated by NK1.1 positive cells. AB - As prostatic epithelia constitutively produce interleukin 7 (IL-7), also responsible for the development and hemostasis of T cells and NK cells, it is important to examine its ability to protect against prostate cancer, and its possible role in future vaccine strategies against prostate cancer. RM-9/mIL-7 cells were used as mIL-7 secreting whole cell vaccine to prevent tumor growth upon a subcutaneous RM-9 challenge in C57bl/6 mice. The RM-9/mIL-7 vaccination effect was studied by CD3, CD4, CD8, or NK1.1 depletion experiments in C57bl/6 mice. RM-9/mIL-7-vaccinated animals showed longer survival times (P<0.0001) than nonvaccinated mice. Depletion of nonvaccinated mice showed a reduction of CD3, CD4, CD8, and NK1.1 cells with 97%, 56%, 99%, and 88%, respectively. RM-9/mIL-7 vaccinated mice, depleted for CD3, CD4, CD8, or NK1.1, all showed shortened host survival times with regard to the nondepleted vaccinated mice group. Moreover, fewer mice survived the tumor challenge compared with the nondepleted RM-9/mIL-7 vaccination group. The shortest survival was observed for NK1.1-depleted mice, which was nearly comparable with survival times of nonvaccinated mice. RM-9/mIL-7 vaccinated mice demonstrated prolonged survival times compared with the survival times of nonvaccinated mice, after tumor challenge administration. The detected immune response against the RM-9 tumor challenge showed to be merely related to the NK1.1-expressing cells, after RM-9/mIL-7 vaccination. IL-7 produced by the prostatic epithelia itself and the role of NK1.1-expressing cells could provide new potential for future immunotherapeutic modalities to recruit immunologic cells against prostate cancer, and its metastases. PMID- 22306902 TI - Efficiency and mechanism of antigen-specific CD8+ T-cell activation using synthetic long peptides. AB - Synthetic long peptides that contain immunogenic T-cell epitopes have been used to induce activation of antigen-specific CD8 T cells in vitro for immune monitoring or adoptive transfer, or in vivo after peptide vaccination. However, the efficiency and mechanisms of presentation of exogenous long peptides in human leukocyte antigen (HLA) class I remain to be elucidated. In this study, we demonstrated that the efficiency of antigen-specific CD8 T-cell activation using extended peptide variants of common viral epitopes is variable. We demonstrated that processing and HLA class I presentation of the long peptides were not dependent on the proteasome and transporter associated with antigen processing, illustrating that the classic route of HLA class I presentation was not required for activation of specific CD8 T cells by exogenous synthetic long peptides. Although long peptides were shown to bind to the relevant HLA class I molecules, peptide trimming was likely to be essential for optimal HLA class I presentation and T-cell activation. As the proteasome was not required for processing of exogenous peptides, it is very likely that peptide trimming was mediated by peptidases, which may be located extracellularly at the cell surface, in the cytosol, endoplasmic reticulum, or in endosomal and lysosomal compartments. Furthermore, the results suggested that processing of the correct minimal peptides was facilitated by binding in HLA class I molecules. This mechanism of HLA-guided processing may be important in HLA class I presentation of exogenous long peptides to induce activation of specific CD8 T cells. PMID- 22306901 TI - Epigenetic modulation to enable antigen-specific T-cell therapy of colorectal cancer. AB - Development of specific immunotherapy for colorectal cancer (CRC) will require identification of antigens selectively or exclusively expressed on CRC cells and strategies to induce and enhance immune responses against these antigenic targets. Cancer-testis (C-T) antigens are proving to be excellent targets for immunotherapy of solid tumors such as melanoma, but their clinical utility for treatment of CRC has to date been limited by their infrequent expression in CRC cells. Here we report that the hypomethylating agent 5-aza-2'-deoxycytidine (DAC) induces expression of NY-ESO-1 and other C-T genes in CRC cells both in vitro and in vivo in a dose-dependent manner but has negligible effects on the expression of C-T genes in normal nontransformed cells such as fibroblasts. The induction by DAC of NY-ESO-1 expression in CRC cells persists over 100 days after DAC exposure and is associated with increased levels of NY-ESO-1 protein. CRC cells exposed to DAC at concentrations that can be readily achieved in vivo are rendered susceptible to major histocompatibility complex-restricted recognition by CD8 NY ESO-1-specific T cells. We also demonstrate that retroviral transduction of polyclonal peripheral blood T cells from a metastatic CRC patient with the T-cell receptor alpha-chain and beta-chain genes encoding a human leukocyte antigen-A2 restricted, NY-ESO-1157-165-specific T-cell receptor can be used to generate both CD8 and CD4 NY-ESO-1157-165-specific T cells that selectively recognize DAC treated CRC but not nontransformed cells. Collectively, these results suggest that the combination of epigenetic modulation and adoptive transfer of genetically engineered T lymphocytes may enable specific immunotherapy for CRC. PMID- 22306903 TI - Imatinib sensitizes T-cell lymphocytes from chronic myeloid leukemia patients to FasL-induced cell death: a brief communication. AB - There is now substantial evidence that imatinib may affect immune responses, especially those mediated by T lymphocytes. Fas (CD95/Apo-1), a cell death receptor, is a key regulator of the immune system. We have explored the consequences of treatment on the Fas system in chronic myeloid leukemia patients treated with imatinib. In comparison with healthy controls, we found not only a mild blood lymphopenia but also impairment of phytohemagglutinin activation in CD4Fas and CD8Fas lymphocytes of imatinib-treated patients. Moreover, these lymphocyte populations were more sensitive to FasL-induced cell death in relation to an increase in Fas expression at the cell surface. Taken together, these results reveal the role of Fas receptor in the lymphopenia observed in patients treated with imatinib, with potential deleterious consequences on antileukemic responses against this immunogenic hematological malignancy. PMID- 22306904 TI - Generation of polyclonal CMV-specific T cells for the adoptive immunotherapy of glioblastoma. AB - Glioblastoma (GBM) is the most common primary brain cancer in adults and is virtually incurable. Recent studies have shown that cytomegalovirus (CMV) is present in majority of GBMs. To evaluate whether the CMV antigens pp65 and IE1, which are expressed in GBMs, could be targeted by CMV-specific T cells, we measured the frequency of T cells targeting pp65 and IE1 in the peripheral blood of a cohort of 11 sequentially diagnosed CMV-seropositive GBM patients, and evaluated whether it was feasible to expand autologous CMV-specific T cells for future clinical studies. All 11 CMV-seropositive GBM patients had T cells specific for pp65 and IE1 in their peripheral blood assessed by IFNgamma enzyme linked immunospot assay. However, the precursor frequency of pp65-specific T cells was decreased in comparison with healthy donors (P=0.001). We successfully reactivated and expanded CMV-specific T cells from 6 out of 6 GBM patients using antigen-presenting cells transduced with an adenoviral vector encoding pp65 and IE1. CMV-specific T-cell lines contained CD4 as well as CD8 T cells, recognized pp65 and IE1 targets and killed CMV-infected autologous GBM cells. Infusion of such CMV-specific T-cell lines may extend the benefits of T-cell therapy to patients with CMV GBMs. PMID- 22306905 TI - PD-1 blockade augments Th1 and Th17 and suppresses Th2 responses in peripheral blood from patients with prostate and advanced melanoma cancer. AB - Negative costimulation on T cells is exploited by both prostate cancer and melanoma to evade antitumor immunity. Blocking such mechanisms restores antitumor immunity as was demonstrated by the improved survival of patients with metastatic melanoma after treatment with an antibody blocking the CTLA-4 inhibitory receptor (ipilimumab). Enhanced expression of another inhibitory immunoreceptor, programmed death-1 (PD-1), and its ligand, PD-L1, was found to correlate with a poor prognosis in prostate cancer and melanoma. PD-1-blocking antibodies are being developed to modulate antitumor immune responses. To support preclinical and clinical development of anti-PD-1 therapy, we sought to develop biomarker assays that can detect the effect of PD-1-blocking agents in whole blood and peripheral blood mononuclear cells. In this study, we assessed the effect of PD-1 blockade in modulating super antigen (staphylococcus enterotoxin B)-induced and recall antigen (tetanus toxoid)-induced T-cell reactivity in vitro using whole blood and peripheral blood mononuclear cells from patients with advanced melanoma, prostate cancer, and healthy controls. PD-1 blockade was found to shift antigen-induced cellular reactivity toward a proinflammatory Th1/Th17 response, as evidenced by enhanced production of interferon gamma, interleukin (IL)-2, tumor necrosis factor alpha, IL-6, and IL-17 and reduced production of the Th2 cytokines IL-5 and IL-13. It is interesting to note that suppression of Th2 responsivity was seen with whole blood cells only from patients with cancer. Taken together, we identified novel biomarker assays that might be used to determine the functional consequences of PD-1 blockade in peripheral blood cells from patients with cancer. How these assays translate to the local antitumor response remains to be established in a clinical setting. PMID- 22306906 TI - Modulation of host natural killer cell functions in breast cancer via prostaglandin E2 receptors EP2 and EP4. AB - Breast malignancies often have high levels of COX-2. The COX-2 product prostaglandin E2 (PGE2) contributes to the high metastatic capacity of breast tumors. Our published data indicate that inhibiting either PGE2 production or PGE2-mediated signaling through the PGE2 receptor EP4 (1 of 4 EP expressed on the malignant cell) reduces metastasis by a mechanism that requires natural killer (NK) cells. Tumor-derived PGE2 and exogenous PGE2 are known to have direct inhibitory effects on NK cell functions, but less is known regarding which EP receptors mediate these effects. We now show that several NK functions (lysis, migration, cytokine production) are compromised in tumor-bearing mice and that tumor-produced PGE2 interferes with NK cell functions. PGE2 inhibits the potential of NK cells to migrate, exert cytotoxic effects, and secrete interferon gamma. The ability of PGE2 to inhibit NK cells from tumor-bearing mice is by acting on EP2 and EP4 receptors. NK cells from tumor-bearing mice were more sensitive to inhibition by EP4 and EP2 agonists compared with endogenous NK cells from healthy mice. PGE2 was inhibitory to most NK functions of either normal or tumor-bearing mice. In contrast, there was a trend for enhanced tumor necrosis factor alpha production in response to PGE2 by NK cells from tumor-bearing mice. We also report that a recently described EP4 antagonist, frondoside A, inhibits breast tumor metastasis in an NK-dependent manner and protects interferon gamma production by NK cells from PGE2-mediated suppression. Taken together these data show that NK functions are depressed in tumor-bearing hosts relative to normal NK cells and that PGE2 suppresses NK functions by acting on EP2 and EP4 receptors. PMID- 22306907 TI - Autologous cytokine-induced killer cell transfusion in combination with gemcitabine plus cisplatin regimen chemotherapy for metastatic nasopharyngeal carcinoma. AB - In this study, we evaluate the efficacy of autologous cytokine-induced killer cells (CIK) transfusion used in combination with gemcitabine and cisplatin (GC) chemotherapy to treat nasopharyngeal carcinoma in patients with distant metastasis after radiotherapy. From September 2007 to August 2008, 60 patients with distant metastasis after radiotherapy were followed up and were randomly divided into 2 groups. The 30 patients in the GC+CIK group were treated with adoptive autologous CIK cell transfusion in combination with GC chemotherapy; the 30 patients in the GC group were treated with chemotherapy alone. Short-term efficacy evaluation revealed that in the GC+CIK group, there were 3 cases of complete remission, 18 cases of partial remission, 2 cases of stabilization of disease, and 7 cases of progression of disease and the total effective rate was 70% (21/30). In the GC group, there were 0 cases of complete remission, 14 cases of partial remission, 3 case of stable disease, and 13 cases of progressive disease and the total effective rate was 46.7% (14/21). Kaplan-Meier survival analysis showed that the overall survival of the GC+CIK group was higher than that of the GC group, but the difference was not significant (P=0.1374, log-rank test). However, the progression-free survival of the GC+CIK group was significantly higher than that of the GC group (P=0.0234, log-rank test). Thus, our study indicated that CIK cell transfusion therapy used in combination with GC chemotherapy may be a more effective treatment for postradiotherapy distant metastasis of nasopharyngeal carcinoma patients. PMID- 22306908 TI - Cytotoxic T-lymphocyte immunotherapy for ovarian cancer: a pilot study. AB - The objective was to evaluate the toxicity and feasibility of intraperitoneal infusion of tumor-specific cytotoxic T lymphocytes (CTL) as therapy for recurrent ovarian cancer, and to determine if repetitive cycles of CTL generation and infusion measurably increases the host's ovarian cancer immune response. In this study, 7 subjects with recurrent ovarian cancer confined to the peritoneal cavity underwent up to 4 cycles, each cycle beginning with a leukapheresis for collection of precursor lymphocytes, which were stimulated in vitro with mucin 1, a tumor-specific antigen found commonly in ovarian cancer cells. The resulting new CTL for each cycle were reintroduced into the host by intraperitoneal infusion. Immunologic parameters (killer cells, cytokine production, memory T lymphocytes, and natural killer cells) were studied. Toxicity, CA-125, and survival data were also evaluated. The tumor marker CA-125 was nonstatistically significantly reduced after the first month of immunotherapy. However, after that it rose. Killer cells, cytokine production, and memory T lymphocytes increased after the first cycle of stimulation, but plateaued or reduced thereafter. The percent of natural killer cells inversely correlated with other immune parameters. Median survival was 11.5 months. One subject is free of disease since December, 2000. Multiple cycles, beyond 1 cycle, of T-cell stimulation followed by adoptive T-cell infusion, may not enhance the in vivo immune response. PMID- 22306909 TI - Tumor-promoting versus tumor-antagonizing roles of gammadelta T cells in cancer immunotherapy: results from a prospective phase I/II trial. AB - Emerging evidence suggests that nitrogen-containing bisphosphonates have direct and indirect anticancer effects including immunomodulatory effects. Using in vivo targeting of bisphosphonate-reactive gammadelta T cells by adding low-dose interleukin-2 to zoledronic acid, we evaluated the safety, pharmacodynamics, and antitumor activity of this immunotherapy approach in 21 adults with advanced malignancies (renal cell carcinoma [RCC], malignant melanoma, and acute myeloid leukemia). A total of 58 treatment cycles were administered and the median number of treatment cycles was 2.7 (range, 1 to 6). The regimen was well tolerated, with no grade 3 to 4 drug-related adverse events, except for fever. No objective responses were observed in both cohorts of solid tumors (RCC and malignant melanoma), whereas 2 patients with acute myeloid leukemia (25%) achieved objective tumor responses (partial remission). Pharmacodynamic analyses showed significant in vivo activation (interferon-gamma production) and expansion of gammadelta T cells in all evaluable patients. High pretreatment serum vascular endothelial growth factor (VEGF) levels and an unexpected increase in VEGF induced by zoledronic acid plus low-dose interleukin-2 were correlated with the lack of a clinical response. In conclusion, this study indicates that immunotherapy-induced VEGF can limit clinical innate tumor immune responses, especially for angiogenesis-dependent solid tumors. Our data challenge the current cellular immunotherapy paradigms in the treatment of cancer. PMID- 22306910 TI - Emerging organic contaminants in groundwater: A review of sources, fate and occurrence. AB - Emerging organic contaminants (EOCs) detected in groundwater may have adverse effects on human health and aquatic ecosystems. This paper reviews the existing occurrence data in groundwater for a range of EOCs including pharmaceutical, personal care, 'life-style' and selected industrial compounds. The main sources and pathways for organic EOCs in groundwater are reviewed, with occurrence data for EOCs in groundwater included from both targeted studies and broad reconnaissance surveys. Nanogram-microgram per litre concentrations are present in groundwater for a large range of EOCs as well as metabolites and transformation products and under certain conditions may pose a threat to freshwater bodies for decades due to relatively long groundwater residence times. In the coming decades, more of these EOCs are likely to have drinking water standards, environmental quality standards and/or groundwater threshold values defined, and therefore a better understanding of the spatial and temporal variation remains a priority. PMID- 22306911 TI - Analytical methods for separating and isolating magnetic nanoparticles. AB - Despite the large body of literature describing the synthesis of magnetic nanoparticles, few analytical tools are commonly used for their purification and analysis. Due to their unique physical and chemical properties, magnetic nanoparticles are appealing candidates for biomedical applications and analytical separations. Yet in the absence of methods for assessing and assuring their purity, the ultimate use of magnetic particles and heterostructures is likely to be limited. In this review, we summarize the separation techniques that have been initially used for this purpose. For magnetic nanoparticles, it is the use of an applied magnetic flux or field gradient that enables separations. Flow based techniques are combined with applied magnetic fields to give methods such as magnetic field flow fractionation and high gradient magnetic separation. Additional techniques have been explored for manipulating particles in microfluidic channels and in mesoporous membranes. Further development of these and new analytical tools for separation and analysis of colloidal particles is critically important to enable the practical use of these, particularly for medicinal purposes. PMID- 22306912 TI - Molecular profiling of indolent human prostate cancer: tackling technical challenges to achieve high-fidelity genome-wide data. AB - The contemporary problem of prostate cancer overtreatment can be partially attributed to the diagnosis of potentially indolent prostate cancers that pose low risk to aged men, and lack of sufficiently accurate risk stratification methods to reliably seek out men with indolent diseases. Since progressive acquisition and accumulation of genomic alterations, both genetic and epigenetic, is a defining feature of all human cancers at different stages of disease progression, it is hypothesized that RNA and DNA alterations characteristic of indolent prostate tumors may be different from those previously characterized in the setting of clinically significant prostate cancer. Approaches capable of detecting such alterations on a genome-wide level are the most promising. Such analysis may uncover molecular events defining early initiating stages along the natural history of prostate cancer progression, and ultimately lead to rational development of risk stratification methods for identification of men who can safely forego treatment. However, defining and characterizing indolent prostate cancer in a clinically relevant context remains a challenge, particularly when genome-wide approaches are employed to profile formalin-fixed paraffin-embedded (FFPE) tissue specimens. Here, we provide the conceptual basis underlying the importance of understanding indolent prostate cancer from molecular profiling studies, identify the key hurdles in sample acquisition and variables that affect molecular data derived from FFPE tissues, and highlight recent progresses in efforts to address these technical challenges. PMID- 22306913 TI - High-risk prostate cancer: is androgen deprivation monotherapy still appropriate? PMID- 22306915 TI - Assessing the anti-tumour properties of Iraqi propolis in vitro and in vivo. AB - The study was designed to evaluate anti-tumour properties of Iraqi propolis collected from Mosul region (M) on HL-60 and HCT-116 cell lines and on HCT-116 in vivo. M induced an inhibitory effect against the proliferation of HL-60 and colony potential of HCT-116 cells. The apoptosis in HL-60 cells was associated with down-regulation of Bcl-2 and activation of Bax, while in HCT-116 cells, necrotic features were observed; size of cells was dramatically increased by swelling of cytoplasm and loss of membrane integrity, cell rupture and release of cellular contents. Analysis of BrdU/DNA cell cycle in both cell lines showed that M induced cell cycle perturbations in both BrdU positive and BrdU negative cells. The exposure of HL-60 to M caused gamma-H2AX in a dose dependent manner and was associated with induction of apoptosis. The experiments in HCT-116 tumor-bearing mice showed that oral administration of propolis at doses that caused no detectable toxicity was associated with a decrease in mitotic cells and an increase in endoreduplications, increased p53 and decreased Ki-67 expression of cells in tumor sections. This study provides the rationale to investigate the potential beneficial effect of propolis in the diet of patients receiving anti cancer therapies. PMID- 22306914 TI - An overview of prostate diseases and their characteristics specific to Asian men. AB - In this paper, we reviewed the features of common prostate diseases, such as benign prostatic hyperplasia (BPH), prostate cancer (PCa) and chronic prostatitis (CP) that are specific to Asian men. Compared to the Westerners, Asians exhibit particular characteristics of prostate diseases. Through summarizing the epidemiology, symptomatology, diagnostics and therapeutics of these diseases, we find that Asians have a lower incidence of PCa than whites, but the incidences of BPH and CP are similar. Asian men with CP often suffer from fewer disease sites, but have a higher frequency of pain during urination rather than after sexual climax. Prostate-specific antigen (PSA) is a widely used marker for the diagnosis of PCa in both Asian and Western countries. Although the PSA level may be lower in Asians, the threshold used is based on whites. After reviewing the treatments available for these diseases, we did not find a fundamental difference between Asians and whites. Furthermore, the selection for the most appropriate treatment based on the individual needs of patients remains a challenge to urologists in Asia. After considering the traits of prostate diseases that are specific to Asian men, we hope to pave the way for the development of specific diagnostic and therapeutic strategies targeted specifically to Asian men. PMID- 22306916 TI - A comparative study on Na2MnPO4F and Li2MnPO4F for rechargeable battery cathodes. AB - Electrochemical properties of A(2)MnPO(4)F (A = Na/Li) were investigated both experimentally and with first principles calculations. A new Li(2)MnPO(4)F phase was successfully synthesized for the first time. A one alkali metal ion reaction occurred reversibly within a reasonable voltage window and a two alkali metal ion reaction took place at higher voltages. PMID- 22306917 TI - A novel dehydrin-like protein from Aspergillus fumigatus regulates freezing tolerance. AB - We recently reported on DprA and DprB, dehydrin-like proteins involved in the protection against oxidative, osmotic and pH stress in Aspergillus fumigatus. A third dehydrin-like gene, DprC, was detected in the genome of the filamentous fungus and repressed during conidial germination. The deletion mutant was impaired in freezing tolerance. The DprC-mediated response was dependent on the SakA MAP kinase pathway, and accordingly, SakA phosphorylation was induced by cold shock. When fused to eGFP, the protein was associated with the vacuoles. PMID- 22306918 TI - Measuring the respiratory chemoreflexes in humans by J. Duffin. PMID- 22306919 TI - Green tea extract can potentiate acetaminophen-induced hepatotoxicity in mice. AB - Green tea extract (GTE) has been advocated as a hepatoprotective compound and a possible therapeutic agent for acetaminophen (APAP) overdose. This study was conducted to determine if GTE can provide protection against APAP-induced hepatotoxicity. Three different exposure scenarios were tested. The first involved administering APAP (150 mg/kg, orally) to mice followed 6h later by GTE (500 or 1000 mg/kg). The other two involved administering GTE prior to the APAP dose. GTE (500 or 1000 mg/kg, orally) was administered 3h prior to APAP (200 mg/kg, orally) or for three consecutive days (once-daily) followed by APAP (300 mg/kg) on the fourth day. Indices of hepatotoxicity were assessed 24h after the APAP dose. GTE potentiated APAP-induced hepatotoxicity when administered after the APAP dose. GTE caused significant glutathione depletion and this effect likely contributed to the observed potentiation. In contrast, GTE provided protection against APAP-induced hepatotoxicity when administered prior to the APAP dose. GTE dramatically decreased APAP covalent binding to protein indicating that less reactive metabolite was available to cause hepatocellular injury. These results highlight the potential for drug-dietary supplement interactions and the importance of testing multiple exposure scenarios to adequately model different types of potential interactions. PMID- 22306920 TI - The protective effects of polyphenols from jujube peel (Ziziphus Jujube Mill) on isoproterenol-induced myocardial ischemia and aluminum-induced oxidative damage in rats. AB - This study was aimed to evaluate the preventive effect of the polyphenols from Chinese jujube peel (Ziziphus jujube Mill. cv. Dongzao) against myocardial injury (MI) induced by isoproterenol (ISO) and biotoxicity of aluminum in rats. The free phenols from jujube peel (JPFP) and the bond phenols from jujube peel (JPBP) were administered to rats by gastric gavage. The results showed that prior administration of JPFP or JPBP remarkably inhibited increases in levels of malondialdehyde (MDA) and activities of Ca(2+)-ATPase and Mg(2+)-ATPase, reductions in activities of superoxide dismutase (SOD), glutathione peroxidase, creatine kinase, lactate dehydrogenase and Na(+)/K(+)-ATPase in the rats induced by ISO. The abnormal changes in morphology of heart muscle and in electrocardiograph induced by ISO treatment were also significantly prevented by the JPFP or JPBP. Treatment with aluminum chloride could cause a significant oxidative damage, including a significant increase in MDA level and decreases in glutathione-S- transferase and SOD activities in brain of the rats, the study showed that gavage with JPFP or JPBP could remarkably alleviate the toxic responses of the rats to aluminum chloride. In summary, our study showed that jujube phenolics can prevent ISO-induced myocardial injury and reduce aluminum toxicity in rats. PMID- 22306921 TI - In vitro antioxidant, antidiabetic and antilipidemic activities of Symplocos cochinchinensis (Lour.) S. Moore bark. AB - Symplocos cochinchinesis is used in Indian system of traditional medicine to treat diabetes mellitus. The present study investigates the in vitro antioxidant, antidiabetic and antilipidemic activities of S. cochinchinensis bark methanolic extract (SCBe) in streptozotocin (STZ) induced diabetic rats. In in vitro studies SCBe showed very good scavenging activity on 2,2-diphenyl-picrylhydrazyl (DPPH) (IC(50) 820.34 +/- 1.74 MUg/ml), hydroxyl (IC(50) 884.19 +/- 0.45 MUg/ml) and nitric oxide (IC(50) 860.21 +/- 1.18 MUg/ml) radicals, as well as high reducing power. SCBe (250 and 500 mg/kg) was administered to STZ (40 mg/kg) induced diabetic rats for 28 days. SCBe showed a significant decrease in blood glucose and significant increase in plasma insulin and liver glycogen levels in treated diabetic rats. Further, SCBe showed antilipidemic activity as evidenced by significant decrease in serum TC, TG, LDL-C levels and significant increase in HDL-C level in treated diabetic rats. SCBe also restored the altered plasma enzymes (SGOT, SGPT and ALP), total protein, urea and creatinine levels to near normal. The action of SCBe was comparable to the antidiabetic drug glibenclamide. Results of this experimental study indicated that SCBe possessed antioxidant, antidiabetic and antilipidemic activities. PMID- 22306922 TI - A new ratiometric ESIPT sensor for detection of palladium species in aqueous solution. AB - An aqueous ratiometric ESIPT sensor with a 87 nM (15.4 ppb) detection limit was successfully synthesized and applied for detection of all oxidation states of palladium species. PMID- 22306923 TI - Single-minded and the evolution of the ventral midline in arthropods. AB - In insects and crustaceans, ventral midline cells are present that subdivide the CNS into bilateral symmetric halves. In both arthropod groups unpaired midline neurons and glial cells have been identified that contribute to the embryonic patterning mechanisms. In the fruitfly Drosophila melanogaster, for example, the midline cells are involved in neural cell fate specification along the dorso ventral axis but also in axonal pathfinding and organisation of the axonal scaffold. Both in insects and malacostracan crustaceans, the bHLH-PAS transcription factor single-minded is the master regulator of ventral midline development and homology has been suggested for individual midline precursors in these groups. The conserved arrangement of the axonal scaffold as well as the regular pattern of neural precursors in all euarthropod groups raises the question whether the ventral midline system is conserved in this phylum. In the remaining euarthropod groups, the chelicerates and myriapods, a single-minded homologue has been identified in the spider Achaearanea tepidariorum (chelicerate), however, the gene is not expressed in the ventral midline but in the median area of the ventral neuroectoderm. Here we show that At-sim is not required for ventral midline development. Furthermore, we identify sim homologues in representatives of arthropods that have not yet been analysed: the myriapod Strigamia maritima and a representative of an outgroup to the euarthropods, the onychophoran Euperipatoides kanangrensis. We compare the expression patterns to the A. tepidariorum sim homologue expression and furthermore analyse the nature of the arthropod midline cells. Our data suggest that in arthropods unpaired midline precursors evolved from the bilateral median domain of the ventral neuroectoderm in the last common ancestor of Mandibulata (insects, crustaceans, myriapods). We hypothesize that sim was expressed in this domain and recruited to ventral midline development. Subsequently, sim function has evolved in parallel to the evolution of midline cell function in the individual Mandibulata lineages. PMID- 22306924 TI - A comprehensive analysis of Delta signaling in pre-gastrular sea urchin embryos. AB - In sea urchin embryos Delta signaling specifies non-skeletogenic mesoderm (NSM). Despite the identification of some direct targets, several aspects of Delta Notch (D/N) signaling remain supported only by circumstantial evidence. To obtain a detailed and more complete image of Delta function we followed a systems biology approach and evaluated the effects of D/N perturbation on expression levels of 205 genes up to gastrulation. This gene set includes virtually all transcription factors that are expressed in a localized fashion by mid-gastrulation, and which thus provide spatial regulatory information to the embryo. Also included are signaling factors and some pigment cell differentiation genes. We show that the number of pregastrular D/N signaling targets among these regulatory genes is small and is almost exclusively restricted to non-skeletogenic mesoderm genes. However, Delta signaling also activates foxY in the small micromeres. As is the early NSM, the small micromeres are in direct contact with Delta expressing skeletogenic mesoderm. In contrast, no endoderm regulatory genes are activated by Delta signaling even during the second phase of delta expression, when this gene is transcribed in NSM cells adjacent to the endoderm. During this phase Delta provides an ongoing input which continues to activate foxY expression in small micromere progeny. Disruption of the second phase of Delta expression specifically abolishes specification of late mesodermal derivatives such as the coelomic pouches to which the small micromeres contribute. PMID- 22306925 TI - Characterizing the time course and nature of attentional disengagement effects. AB - Visual features of fixated but irrelevant items contribute to both how long overt attention dwells at a location and to decisions regarding the location of subsequent attention shifts (Boot & Brockmole, 2010; Brockmole & Boot, 2009). Fixated but irrelevant search items that share the color of the search target delay the deployment of attention. Furthermore, eye movements are biased to distractors that share the color of the currently fixated item. We present a series of experiments that examined these effects in depth. Experiment 1 explored the time course of disengagement effects. Experiments 2 and 3 explored the generalizability of disengagement effects by testing whether they could be observed when participants searched for targets defined by form instead of color. Finally, Experiment 4 validated the disengagement paradigm as a measure of disengagement and ruled out alternative explanations for slowed saccadic reaction times. Results confirm and extend our understanding of the influence of features within the focus of attention on when and where attention will shift next. PMID- 22306926 TI - Morphometric X-ray absorptiometry (MXA) vertebral heights in Spanish women. PMID- 22306927 TI - The relationship between serum ghrelin and body composition with bone mineral density and QUS parameters in subjects with Rett syndrome. AB - Several studies have reported that females with Rett's syndrome frequently have marked decreases in bone mineral density (BMD). However, the pathogenesis of impaired bone status in RTT girls remains controversial. This study aimed to investigate whether ghrelin, an orexigenic peptide secreted by the stomach, was associated with body composition parameters, bone mineral density and quantitative ultrasound (QUS) in girls with Rett's syndrome. In 123 Rett girls (13.6+/-8.2 years) and in 55 similar age range controls we evaluated ghrelin serum levels, 25OHD, quantitative ultrasound parameters at phalanxes by Bone Profiler-IGEA (amplitude dependent speed of sound: AD-SoS and bone transmission time: BTT), total body bone mineral density (BMD-WB) by Hologic QDR 4500. Whole body mineral content (BMC-WB), BMC-WB/height, fat mass (FM), fat percentage and lean mass (LM) were determined by using the same DXA device. We found that serum ghrelin levels were significantly higher in the Rett patients with respect to the control group (p<0.05). In Rett girls ghrelin serum levels were inversely correlated with both age (R(2)=0.17, p<0.001) and BMI (R(2)=0.14, p<0.001). Moreover, in Rett subjects the values of BMD-WB, BMC-WB, BMC-WB/height and QUS parameters were significantly lower than in control subjects. Fat mass and lean mass were lower in Rett subjects than in controls, but the difference reached the statistical significance only for lean mass. In Rett girls ghrelin serum levels were not predictors of bone status. Instead, we found that in Rett subjects, lean mass, age and 25OHD were significant independent predictors of BMC-WB/h, whereas both age and height were independent predictors of BMD-WB. Moreover, AD-SoS was predicted by age, fat percentage and height; while BTT was predicted only by height. In conclusion, our findings indicate that ghrelin levels were higher in Rett girls with respect to healthy controls, and negatively associated with both DXA and QUS parameters. However, in our study ghrelin was not found to be an independent predictor of bone mass, so supporting the hypothesis that ghrelin is elevated in Rett subjects in a compensatory manner. PMID- 22306928 TI - The association between fat and lean mass and bone mineral density: the Healthy Twin Study. AB - The potential beneficial effects of increased body weight on bone mineral density (BMD) conflict with the adverse effects of obesity on various health outcomes, necessitating more specific evaluations of the association between each body component and BMD. In the present study, we evaluated associations of lean mass (LM) and fat mass (FM) with BMD in a Korean sample consisting of a total of 1782 men and women whose mean (standard deviation) age was 43.2 (12.6) years. They were selected from the Healthy Twin Study, a nationwide Korean twin and family study. BMD, FM and LM were measured using dual-energy X-ray absorptiometry. Quantitative genetic analysis and linear mixed analysis were performed with respect to familial relationships and a wide range of probable covariates. Linear mixed analysis revealed that BMD was positively associated with both FM and LM at each region of BMD measurement (whole body, spine, arms, and legs) in men, premenopausal women, and postmenopausal women. However, the association with BMD was stronger for LM than FM. Both LM and FM had positive genetic correlations with BMD at each region, although the correlation with BMD tended to be stronger for LM than FM. Together, these findings suggest that increased LM, rather than FM, is more beneficial for BMD in the Korean population and warrants further study of the common genetic determinants of BMD and body composition. PMID- 22306929 TI - Molecular dynamics simulations of the Ca2+-pump: a structural analysis. AB - We report large scale molecular dynamics computer simulations, ~100 ns, of the ion pump Ca(2+)-ATPase immersed in a 1-palmitoyl-2-oleoyl-sn-glycero-3 phosphocholine (POPC) bilayer. The structure simulated here, E1, one of the several conformations resolved using X-ray diffraction techniques, hosts two Ca(2+)-ions in the hydrophobic domain. Our results indicate that protonated residues lead to stronger ion-residue interactions, supporting previous conclusions regarding the sensitivity of the Ca(2+) behaviour to the protonated state of the amino acid binding sites. We also investigate how the protein perturbs the bilayer structure. We show that the POPC bilayer is ~12% thinner than the pure bilayer, near the protein surface. This perturbation decays exponentially with the distance from the protein with a characteristic decay length of 0.8 nm. We find that the projected area per lipid also decreases near the protein. Using an analytical model we show that this change in the area is only apparent and it can be explained by considering the local curvature of the membrane. Our results indicate that the real area per lipid near the protein is not significantly modified with respect to the pure bilayer result. Further our results indicate that the local deformation of the membrane around the protein might be compatible with the enhanced protein activity observed in experiments over a narrow range of membrane thicknesses. PMID- 22306930 TI - Quantitative evidence for the benefits of Moving the Goalposts, a Sport for Development project in rural Kenya. AB - Sport for Development has many reported benefits, but quantitative evidence of the impact of these interventions in Low Income Countries remains sparse. A new monitoring and evaluation toolkit was used in a cross-sectional survey at Moving the Goalposts (MTG), a football project aiming to empower young Kenyan women. We wished to determine empirically whether increased membership duration brought increased benefits. MTG selected and translated toolkit items consistent with the organisation's strategic aims. We collected 333 completed questionnaires at 15 sites. Psychometric validation revealed some reliable scales; remaining items were scored separately. Scores were sensitive to differences between members defined by sociodemographic and site characteristics. Bivariate and multiple regression analyses showed that increased membership duration brought increasing benefits across several domains (perceived lifeskills; social life; insights about HIV/AIDS; outcomes related to female empowerment). Improved leadership skills were mainly age-related. Members attending more established sites experienced greater benefits, but members at more and less accessible sites benefitted similarly. Positive thoughts and feelings were related not to membership duration, but to how long a site had been operating. This indicates the importance of creating a positive culture over time. This cross-sectional study provides quantitative evidence for the benefits of Sport for Development initiatives. PMID- 22306931 TI - Development of an intervention programme to encourage high school students to stay in school for lunch instead of eating at nearby fast-food restaurants. AB - Many schools have recently adopted food policies and replaced unhealthy products by healthy foods. Consequently, adolescents are more likely to consume a healthy meal if they stay in school for lunch to eat a meal either prepared at home or purchased in school cafeterias. However, many continue to eat in nearby fast-food restaurants. The present paper describes the development of a theory-based intervention programme aimed at encouraging high school students to stay in school for lunch. Intervention Mapping and the Theory of Planned Behaviour served as theoretical frameworks to guide the development of a 12-week intervention programme of activities addressing intention, descriptive norm, perceived behavioural control and attitude. It was offered to students and their parents with several practical applications, such as structural environmental changes, and educational activities, such as audio and electronic messages, posters, cooking sessions, pamphlets, improvisation play theatre, quiz, and conferences. The programme considers theoretical and empirical data, taking into account specific beliefs and contexts of the target population. This paper should help programme planners in the development of appropriate interventions addressing the problem. PMID- 22306932 TI - Expert panel reviews of research centers: the site visit process. AB - Site visits are used extensively in a variety of settings within the evaluation community. They are especially common in making summative value decisions about the quality and worth of research programs/centers. However, there has been little empirical research and guidance about how to appropriately conduct evaluative site visits of research centers. We review the processes of two site visit examples using an expert panel review: (1) a process to evaluate four university research centers and (2) a process to review a federally sponsored research center. A set of 14 categories describing the expert panel review process was obtained through content analysis and participant observation. Most categories were addressed differently through the two processes highlighting the need for more research about the most effective processes to use within different contexts. Decisions about how to structure site visits appear to depend on the research context, practical considerations, the level at which the review is being conducted and the intended impact of the report. Future research pertaining to the selection of site visitors, the autonomy of the visitors in data collection and report writing, and the amount and type of information provided would be particularly valuable. PMID- 22306933 TI - Infectious complications in GSW's through the gastrointestinal tract into the spine. AB - BACKGROUND: Trans-gastrointestinal tract GSW's to the spine are devastating injuries with significant potential for infectious complications. We sought to address antimicrobial management of these injuries. METHODS: We retrospectively analysed all patients with penetrating trauma through the GI tract into the spine admitted to a level I trauma centre from 1/02 to 12/09. Patients were excluded if they died within 24h. Patients received 24-48 h of peri-operative prophylactic antibiotics, except in damage control where antibiotics were continued until packs were removed. RESULTS: 51 patients were included. 94% were male with a mean age of 27 years. The mean ISS was 28 (9-50). The mean length of stay was 19 days (3-53) and mortality was 9.8%. The mean follow up period was 277 days (0-1765). There were 12 gastric, 25 small bowel, 26 colonic, and 4 esophageal injuries. There were 48 exploratory laparotomies, of which 12 were damage control procedures. 18 patients had no infections. There were 20 abdominal infections and 7 surgical wound infections. There were 23 infections not related to the abdomen. One patient developed a CNS infection 4 days after discharge despite receiving a two week course of piperacillin/tazobactam for Escherichia coli bacteremia during his initial hospital stay. There were no other CNS infections. CONCLUSION: Despite the potential for significant deep infections of the spine, standard antimicrobial prophylaxis is sufficient for the initial management of these patients. PMID- 22306934 TI - Resuscitation volume in paediatric non-haemorrhagic blunt trauma. AB - INTRODUCTION: Trauma is a major cause of paediatric morbidity and mortality, yet knowledge of fluid resuscitation is limited. Our objectives were to determine current practises in resuscitation volume (RV) administered to paediatric non haemorrhagic (NH) blunt trauma patients and to identify fluid related complications. METHODS: We examined data from 139 trauma patients 1-17 years of age with an injury severity score >= 12 resuscitated at a Trauma-designated Children's Hospital. Patients were separated into discreet groups based on ATLS age-dependent vital functions: toddler/preschooler (1-5 years), school age (6-12 years) and adolescent (13-17 years). RESULTS: The median RV (total fluid intake maintenance fluid intake) in ml/kg over the first 24h from the time of trauma by age was: 24 (IQR=19-47; 1-5 years); 26 (IQR=15-36; 6-12 years); and 22 (IQR=14 42; 13-17 years). The differences in RV/kg/24h following NH trauma was not significantly different between age groups (p=0.41). Urine output over the 24h ranged from 2.5 (IQR=1.9-3.3; lower age group) to 1.8 (IQR=1.2-2.4; upper age group) ml/kg/h; greater than the ATLS recommended age-dependent targets. Haematocrit was the only significant independent predictor of RV/kg/24h (p<0.001). Fluid-related complications attributable to RV were identified in 12% (n=17/139) of patients, and included ascites (8%; n=11/139) and/or pleural effusion(s) (9%; n=13/139). Patients with fluid-related complications received significantly more RV in ml/kg/24h (42, IQR=27-76) than those without complications (22, IQR=14-36; p=0.001). CONCLUSIONS: The range of median RV administered to paediatric NH blunt trauma patients with ISS >= 12 was 22-26 ml/kg/24h. The RV administered was excessive based on high urine outputs and the presence of fluid-related complications. Further evaluation of RV triggers and endpoints used by paediatric traumatologists is required. PMID- 22306935 TI - Traumatic atlantoaxial rotatory subluxation (TAARS) in adults: a report of two cases and literature review. PMID- 22306937 TI - Use of a screening tool to determine nonadherent behavior in inflammatory bowel disease. AB - OBJECTIVES: Nonadherence is an issue in the management of inflammatory bowel disease (IBD), and no validated screening tool is available. We aimed to determine whether scores from a self-reported adherence survey correlated with pharmacy refill data as a reliable measure of medication adherence. METHODS: We used the eight item, self-reported Morisky Medication Adherence Scale. Each question is worth a point, with a maximum score of 8. Pharmacies were contacted for refill information for the previous 3 months, then 3 and 6 months from enrollment. Refill data were recorded for each time interval as the medication possession ratio (MPR); adherence was defined as >80%. Analysis of variance was used to determine the relationship between survey scores and MPR by drug class. RESULTS: One hundred fifty outpatients were enrolled, of whom 94 had Crohn's disease and 56 had ulcerative colitis; 89 were female. At baseline, 47% of patients were on 5-aminosalicylic acid (5-ASA), 54% an immunomodulator, 15% infliximab, 8% an injectable biologic, and 6% budesonide. The median adherence score was 7. Fifty-two percent stated they "rarely" missed a dose of medication. The median adherence score, as defined by refill data, ranged from 0% (injectable biologic) to 75% (infliximab) by drug class. Only those on an immunomodulator had a survey score that positively correlated with adherence. CONCLUSIONS: Only those on a thiopurine were likely to have a score predicting adherence behavior. Adherence to therapy for IBD is complex and cannot be predicted reliably by a self-reported survey tool validated for other chronic conditions. PMID- 22306938 TI - Darwinian dyspepsia: an extraordinary scientist, an ordinary illness, great dignity. PMID- 22306939 TI - Images of the month. A jejunal plasmacytoma causing significant hemorrhage. PMID- 22306944 TI - Serum IGF-1 linking visceral obesity with esophageal adenocarcinoma: unconvincing evidence. AB - There is a strong positive association between body mass index (BMI) and risk of esophageal adenocarcinoma. This is likely to be largely or entirely explained by the established association between central obesity and gastroesophageal reflux and between the latter and risk of esophageal adenocarcinoma. Visceral fat is also metabolically active and there is interest in the possibility that humoral factors released by this fat might promote esophageal carcinogenesis. Insulin growth factor I (IGF-1) has been studied but current data do not support circulating total IGF-1 as a humoral factor linking BMI and esophageal carcinogenesis. PMID- 22306945 TI - Abnormal immune regulation and low-grade inflammation in IBS: does one size fit all? AB - Evidences suggest that there is low-grade inflammation in the colonic mucosa and/or a state of immune activation in patients with irritable bowel syndrome (IBS). Results from available studies are inconsistent mainly because of differences in measures, methodologies and study populations. In this issue, Chang et al. evaluated a comprehensive set of cytokines, immune markers and immune-related cells in patients with non post infectious IBS (non PI-IBS) and controls. The main finding was a lower expression of the mRNA of the anti inflammatory IL-10 cytokine in the colonic mucosa of women with non PI-IBS without any differences in the cell counts. These results suggest that in non PI IBS, there is altered immune regulation/activation without evidence of low-grade mucosal inflammation. Further, PI and non PI-IBS may be associated with different alterations in immune function/activation. PMID- 22306946 TI - Pancreas divisum does not cause pancreatitis, but associates with CFTR mutations. AB - Bertin et al. partially dispel arguments that pancreas divisum (PD) causes pancreatitis, but fascinatingly indicate that PD associates with CFTR gene mutations predisposing to pancreatitis. This association, however, does not definitely confer a pathophysiological role for PD in pancreatitis but may denote that PD co-mingles with CFTR mutations without influencing pancreatitis or CFTR mutations influence pancreatic duct embryogenesis. We advise "idiopathic pancreatitis" patients with PD to undergo genetic testing. In lieu of CFTR mutations undertake no endoscopic/surgical procedure; if CFTR mutations are found, then refer patients for genetic counseling and withhold endoscopic/surgical therapy unless randomized studies show benefit. PMID- 22306947 TI - Efficacy of certolizumab pegol in Crohn's disease: response to ford et Al. PMID- 22306949 TI - GERD diagnosis: pretest probability and the "gold" standard alter outcome. PMID- 22306951 TI - Inflammatory bowel disease: relevant history-taking is more important than routine HIV testing. PMID- 22306953 TI - Withdrawing PPI therapy: response to Metz et al. PMID- 22306955 TI - Usefulness of 4D MRI flow imaging to control TIPS function. PMID- 22306956 TI - How early should endoscopy be performed in suspected upper gastrointestinal bleeding? PMID- 22306959 TI - Dispersal of the radionuclide caesium-137 (137Cs) from point sources in the Barents and Norwegian Seas and its potential contamination of the Arctic marine food chain: coupling numerical ocean models with geographical fish distribution data. AB - Dispersal of (137)Cs from Komsomolets and K-159 is simulated using realistic rates and hypothetical scenarios. Furthermore, spatiotemporal (137)Cs concentrations in Northeast Arctic cod and capelin are estimated based on survey data. The results indicate that only pulse discharges from K-159 will cause concentrations of (137)Cs in cod muscle exceeding the intervention level of 600 Bq/kg fresh weight. A discharge of >=10% of the (137)Cs-inventory will result in concentrations in muscle of cod exceeding the intervention level for approximately two years. In fact, a discharge of 10% of the (137)Cs-inventory results in an overlap of 8-30% between the different size groups of cod and levels that exceed the intervention level during the first year after the discharge. For capelin, individuals less than one year old during the first year after a discharge are more likely to be severely affected by discharges comprising >=50% of the inventory. PMID- 22306960 TI - VUF10166, a novel compound with differing activities at 5-HT3A and 5-HT3AB receptors. AB - The actions of a novel, potent 5-HT3 receptor ligand, [2-chloro-(4 methylpiperazine-1-yl)quinoxaline (VUF10166)], were examined at heterologously expressed human 5-HT3A and 5-HT3AB receptors. VUF10166 displaced [3H]granisetron binding to 5-HT3A receptors expressed in human embryonic kidney cells with high affinity (K(i) = 0.04 nM) but was less potent at 5-HT3AB receptors (K(i) = 22 nM). Dissociation of [3H]granisetron in the presence of VUF10166 was best fit with a single time constant (t(1/2) = 53 min) at 5-HT3A receptors, but with two time constants (t(1/2) = 55 and 2.4 min) at 5-HT3AB receptors. Electrophysiological studies in oocytes revealed that VUF10166 inhibited 5-HT induced responses at 5-HT3A receptors at nanomolar concentrations, but inhibition and recovery were too slow to determine an IC50. At 5-HT3AB receptors, inhibition and recovery were faster, yielding an IC50 of 40 nM. Cysteine substitutions in the complementary (-), but not the principal (+), face of the 5-HT3B subunit produced heteromeric receptors in which the actions of VUF10166 resembled those at homomeric receptors. At 5-HT3A receptors, VUF10166 at higher concentrations also behaved as a partial agonist (EC50 = 5.2 MUM; R(max) = 0.24) but did not elicit significant responses at 5-HT3AB receptors at <=100 MUM. Thus, we propose that VUF10166 binds to the common A+A- site of both receptor types and to a second A+B- modulatory site in the heteromeric receptor. The ability of VUF10166 to distinguish between 5-HT3A and 5-HT3AB receptors could help evaluate differences between these receptor types and has potential therapeutic value. PMID- 22306961 TI - High-definition imaging of circulating tumor cells and associated cellular events in non-small cell lung cancer patients: a longitudinal analysis. AB - Sampling circulating tumor cells (CTCs) from peripheral blood is ideally accomplished using assays that detect high numbers of cells and preserve them for downstream characterization. We sought to evaluate a method using enrichment free fluorescent labeling of CTCs followed by automated digital microscopy in patients with non-small cell lung cancer. Twenty-eight patients with non-small cell lung cancer and hematogenously seeded metastasis were analyzed with multiple blood draws. We detected CTCs in 68% of analyzed samples and found a propensity for increased CTC detection as the disease progressed in individual patients. CTCs were present at a median concentration of 1.6 CTCs ml-1 of analyzed blood in the patient population. Higher numbers of detected CTCs were associated with an unfavorable prognosis. PMID- 22306962 TI - Effect of acute exercise on executive function in children with attention deficit hyperactivity disorder. AB - This study was conducted to determine the effect of acute aerobic exercise on executive function in children with attention deficit hyperactivity disorder (ADHD). Forty children with ADHD were randomly assigned into exercise or control groups. Participants in the exercise group performed a moderate intensity aerobic exercise for 30 min, whereas the control group watched a running/exercise-related video. Neuropsychological tasks, the Stroop Test and the Wisconsin Card Sorting Test (WCST), were assessed before and after each treatment. The results indicated that acute exercise facilitated performance in the Stroop Test, particularly in the Stroop Color-Word condition. Additionally, children in the exercise group demonstrated improvement in specific WCST performances in Non-perseverative Errors and Categories Completed, whereas no influences were found in those performances in the control group. Tentative explanations for the exercise effect postulate that exercise allocates attention resources, influences the dorsolateral prefrontal cortex, and is implicated in exercise-induced dopamine release. These findings are promising and additional investigations to explore the efficacy of exercise on executive function in children with ADHD are encouraged. PMID- 22306963 TI - Facile access to versatile fluorescent carbon dots toward light-emitting diodes. AB - We report the facile synthesis of carbon dots with tunable fluorescence from unzipping of photonic crystals and their application in LEDs, which may provide an insight into the creation of multifunctional carbon dots adapted for various applications such as in optoelectronics, sensing, or bioimaging. PMID- 22306964 TI - Proteomic analysis of secretion from human transplanted submandibular gland replacing lacrimal gland with severe keratoconjunctivitis sicca. AB - PURPOSE: Proteomic analysis of secretions from transplanted or non-transplanted submandibular glands in patients with severe keratoconjunctivitis sicca and tears from normal eyes. EXPERIMENTAL DESIGN: Secretions from submandibular glands transplanted to replace lacrimal glands and non-transplanted submandibular glands were collected at 1year from 5 patients with severe keratoconjunctivitis sicca undergoing transplantation, and tears were collected from 3 normal subjects. 2-D electrophoresis (2-DE), then mass spectrometry was used to identify proteins. Western blot analysis was used to confirm protein expression. RESULTS: We identified 34 and 11 distinct proteins in the saliva from transplanted submandibular glands and tears, respectively. The saliva from transplanted submandibular glands contained almost all the proteins abundant in tear fluid. The functions of identified proteins in the saliva from transplanted submandibular gland were mainly immune response and anti-bacterial. In total, 7 proteins showed differential expression between the saliva of transplanted and non-transplanted submandibular glands. The upregulation of short palate, lung and nasal epithelium carcinoma-associated protein 2 and carbonic anhydrase VI was confirmed by Western blot analysis. CONCLUSIONS: Identified proteins in saliva from transplanted submandibular glands may protect ocular structures. These findings can help in understanding the functional status of transplanted submandibular glands. PMID- 22306965 TI - Toxicokinetics of domoic acid in the fetal rat. AB - Domoic acid (DA) is a potent neurotoxin that has both marine wildlife and human health impacts, including developmental effects during prenatal exposure in rodent models. However, little is known regarding DA toxicokinetics in the fetal unit during maternal-fetal transfer. Tissue distribution and toxicokinetics of DA were investigated in pregnant rats and their pups just prior to birth at gestational day 20. Pregnant Sprague Dawley rats were given an intravenous dose of 1.0 mg DA/kg and samples of maternal plasma, fetal plasma, placenta, amniotic fluid and fetal brain were taken at intervals over 24 h. Toxicokinetic parameters were determined using WinNonLin software analysis. Maternal plasma DA log concentration-time curves fit a two compartment pharmacokinetic profile, with alpha and beta half-lives of elimination of 26.9 and 297 min, respectively. Placenta had a C(max) of 752 ng/mL and a terminal half-life of 577 min. Maternal fetal transfer between the plasma compartments was 31% with a fetal plasma C(max) of 86 ng/mL at 60 min and terminal half-life of 553 min. Amniotic fluid and fetal brain had overall averages of 27+/-12 ng/mL and 8.12 ng/g, respectively, and did not show evidence of elimination over 24 h. The longer fetal retention of DA, particularly in amniotic fluid, indicates that the fetus may be continually re exposed during gestation, which could potentially lead to a disease state even at small exposure dose. This has implications for the California sea lions (Zalophus californianus), which exhibit an epilepsy-like disease that arises months after DA producing blooms. PMID- 22306966 TI - Simvastatin disrupts cytoskeleton and decreases cardiac fibroblast adhesion, migration and viability. AB - Statins reduce the isoprenoids farnesyl and geranylgeranyl pyrophosphate, essential intermediates, which control a diversity of cellular events such as cytoskeleton integrity, adhesion, migration and viability. Cardiac fibroblasts are the major non-myocyte cell constituent in the normal heart, and play a key role in the maintenance of extracellular matrix. The effects of simvastatin on cardiac fibroblast processes previously mentioned remain unknown. Our aims were to investigate the effects of simvastatin on cytoskeleton structure and focal adhesion complex assembly and their relationships with cell adhesion, migration and viability in cultured cardiac fibroblasts. To this end, cells were treated with simvastatin for 24 h and changes in actin cytoskeleton, levels of vimentin and paxillin as well as their subcellular localization were analyzed by Western blot and immunocytochemistry, respectively. Cell adhesion to plastic or collagen coated dishes, migration in Transwell chambers, and cell viability were analyzed after simvastatin treatment. Our results show that simvastatin disrupts actin cytoskeleton and focal adhesion complex evaluated by phalloidin stain and immunocytochemistry for paxillin and vinculin. All these effects occurred by a cholesterol synthesis-independent mechanism. Simvastatin decreased cell adhesion, migration and viability in a concentration-dependent manner. Finally, simvastatin decreased angiotensin II-induced phospho-paxillin levels and cell adhesion. We concluded that simvastatin disrupts cytoskeleton integrity and focal adhesion complex assembly in cultured cardiac fibroblasts by a cholesterol-independent mechanism and consequently decreases cell migration, adhesion and viability. PMID- 22306967 TI - Dermal application of nitric oxide releasing acidified nitrite-containing liniments significantly reduces blood pressure in humans. AB - Vascular ischemic diseases, hypertension, and other systemic hemodynamic and vascular disorders may be the result of impaired bioavailability of nitric oxide (NO). NO but also its active derivates like nitrite or nitroso compounds are important effector and signal molecules with vasodilating properties. Our previous findings point to a therapeutical potential of cutaneous administration of NO in the treatment of systemic hemodynamic disorders. Unfortunately, no reliable data are available on the mechanisms, kinetics and biological responses of dermal application of nitric oxide in humans in vivo. The aim of the study was to close this gap and to explore the therapeutical potential of dermal nitric oxide application. We characterized with human skin in vitro and in vivo the capacity of NO, applied in a NO-releasing acidified form of nitrite-containing liniments, to penetrate the epidermis and to influence local as well as systemic hemodynamic parameters. We found that dermal application of NO led to a very rapid and significant transepidermal translocation of NO into the underlying tissue. Depending on the size of treated skin area, this translocation manifests itself through a significant systemic increase of the NO derivates nitrite and nitroso compounds, respectively. In parallel, this translocation was accompanied by an increased systemic vasodilatation and blood flow as well as reduced blood pressure. We here give evidence that in humans dermal application of NO has a therapeutic potential for systemic hemodynamic disorders that might arise from local or systemic insufficient availability of NO or its bio-active NO derivates, respectively. PMID- 22306968 TI - Chiral-at-metal complexes and their catalytic applications in organic synthesis. AB - This tutorial review provides an introduction to the synthesis and characterization of chiral-at-metal complexes and their catalytic application in organic transformations. The synthetic access to these architectures either via chiral resolution or by employment of chiral ligands is described, characterization techniques for the complexes are referenced and the application of the R/S nomenclature is explained. Racemization and epimerization processes are often observed for the title compounds; the article gives mechanistic insights to these processes and describes how to recognize and document them. Finally, key catalytic applications in organic synthesis are presented and how the molecular architectures of the chiral-at-metal complexes lead to stereodifferentiation and, thus to enantiomeric excesses in the products. PMID- 22306969 TI - A baculovirus photolyase with DNA repair activity and circadian clock regulatory function. AB - Cryptochromes and photolyases belong to the same family of flavoproteins but, despite being structurally conserved, display distinct functions. Photolyases use visible light to repair ultraviolet-induced DNA damage. Cryptochromes, however, function as blue-light receptors, circadian photoreceptors, or repressors of the CLOCK/BMAL1 heterodimer, the transcription activator controlling the molecular circadian clock. Here, we present evidence that the functional divergence between cryptochromes and photolyases is not so univocal. Chrysodeixis chalcites nucleopolyhedrovirus possesses 2 photolyase-like genes: phr1 and phr2. We show that PHR1 and PHR2 are able to bind the CLOCK protein. Only for PHR2, however, the physical interaction with CLOCK represses CLOCK/BMAL1-driven transcription. This result shows that binding of photolyase per se is not sufficient to inhibit the CLOCK/BMAL1 heterodimer. PHR2, furthermore, affects the oscillation of immortalized mouse embryonic fibroblasts, suggesting that PHR2 can regulate the molecular circadian clock. These findings are relevant for further understanding the evolution of cryptochromes and photolyases as well as behavioral changes induced in insects by baculoviruses. PMID- 22306970 TI - Microarray analysis of natural socially regulated plasticity in circadian rhythms of honey bees. AB - Honey bee workers care for ("nurse") the brood around the clock without circadian rhythmicity, but then they forage outside with strong circadian rhythms and a consolidated nightly rest. This chronobiological plasticity is associated with variation in the expression of the canonical "clock genes" that regulate the circadian clock: nurse bees show no brain rhythms of expression, while foragers do. These results suggest that the circadian system is organized differently in nurses and foragers. Nurses switch to activity with circadian rhythms shortly after being removed from the hive, suggesting that at least some clock cells in their brain continue to measure time while in the hive. We performed a microarray genome-wide survey to determine general patterns of brain gene expression in nurses and foragers sampled around the clock. We found 160 and 541 transcripts that exhibited significant sinusoidal oscillations in nurses and foragers, respectively, with peaks of expression distributed throughout the day in both task groups. Consistent with earlier studies, transcripts of genes involved in circadian rhythms, including Clockwork Orange that has not been studied before in bees, oscillated in foragers but not in nurses. The oscillating transcripts also were enriched for genes involved in the visual system, "development" and "response to stimuli" (foragers), "muscle contraction" and "microfilament motor gene expression" (nurses), and "generation of precursor metabolites" and "energy" (both). Transcripts of genes encoding P450 enzymes oscillated in both nurses and foragers but with a different phase. This study identified new putative clock controlled genes in the honey bee and suggests that some brain functions show circadian rhythmicity even in nurse bees that are active around the clock. PMID- 22306971 TI - Rhodopsin 5- and Rhodopsin 6-mediated clock synchronization in Drosophila melanogaster is independent of retinal phospholipase C-beta signaling. AB - Circadian clocks of most organisms are synchronized with the 24-hour solar day by the changes of light and dark. In Drosophila, both the visual photoreceptors in the compound eyes as well as the blue-light photoreceptor Cryptochrome expressed within the brain clock neurons contribute to this clock synchronization. A specialized photoreceptive structure located between the retina and the optic lobes, the Hofbauer-Buchner (H-B) eyelet, projects to the clock neurons in the brain and also participates in light synchronization. The compound eye photoreceptors and the H-B eyelet contain Rhodopsin photopigments, which activate the canonical invertebrate phototransduction cascade after being excited by light. We show here that 2 of the photopigments present in these photoreceptors, Rhodopsin 5 (Rh5) and Rhodopsin 6 (Rh6), contribute to light synchronization in a mutant (norpA(P41) ) that disrupts canonical phototransduction due to the absence of Phospholipase C-beta (PLC-beta). We reveal that norpA(P41) is a true loss-of function allele, resulting in a truncated PLC-beta protein that lacks the catalytic domain. Light reception mediated by Rh5 and Rh6 must therefore utilize either a different (nonretinal) PLC-beta enzyme or alternative signaling mechanisms, at least in terms of clock-relevant photoreception. This novel signaling mode may distinguish Rhodopsin-mediated irradiance detection from image forming vision in Drosophila. PMID- 22306972 TI - The ability to entrain to long photoperiods differs between 3 Drosophila melanogaster wild-type strains and is modified by twilight simulation. AB - The ability to adapt to different environmental conditions including seasonal changes is a key feature of the circadian clock. Here, we compared the ability of 3 Drosophila melanogaster wild-type strains to adapt rhythmic activity to long photoperiods simulated in the laboratory. Fruit flies are predominantly crepuscular with activity bouts in the morning (M) and evening (E). The M peak follows dawn and the E peak follows dusk when the photoperiod is extended. We show that this ability is restricted to a certain extension of the phase angle between M and E peaks, such that the E peak does not delay beyond a certain phase under long days. We demonstrate that this ability is significantly improved by simulated twilight and that it depends additionally on the genetic background and the ambient temperature. At 20 degrees C, the laboratory strain CantonS had the most flexible phase angle between M and E peaks, a Northern wild-type strain had an intermediate one, and a Southern wild-type strain had the lowest flexibility. Furthermore, we found that the 3 strains differed in clock light sensitivity, with the CantonS and the Northern strains more light sensitive than the Southern strain. These results are generally in accord with the recently discovered polymorphisms in the timeless gene (tim) that affect clock light sensitivity. PMID- 22306973 TI - Rapid assessment of sleep-wake behavior in mice. AB - Sleep is a fundamental biological rhythm involving the interaction of numerous brain structures and diverse neurotransmitter systems. The primary measures used to define sleep are the electroencephalogram (EEG) and electromyogram (EMG). However, EEG-based methods are often unsuitable for use in high-throughput screens as they are time-intensive and involve invasive surgery. As such, the dissection of sleep mechanisms and the discovery of novel drugs that modulate sleep would benefit greatly from further development of rapid behavioral assays to assess sleep in animal models. Here is described an automated noninvasive approach to evaluate sleep duration, latency, and fragmentation using video tracking of mice in their home cage. This approach provides a high correlation with EEG/EMG measures under both baseline conditions and following administration of pharmacological agents. Moreover, the dose-dependent effects of sedatives, stimulants, and light can be readily detected. This approach is robust yet relatively inexpensive to implement and can be easily incorporated into ongoing screening programs to provide a powerful first-pass screen for assessing sleep and allied behaviors. PMID- 22306974 TI - Forced desynchronization of activity rhythms in a model of chronic jet lag in mice. AB - We studied locomotor activity rhythms of C57/Bl6 mice under a chronic jet lag (CJL) protocol (ChrA(6/2) ), which consisted of 6-hour phase advances of the light-dark schedule (LD) every 2 days. Through periodogram analysis, we found 2 components of the activity rhythm: a short-period component (21.01 +/- 0.04 h) that was entrained by the LD schedule and a long-period component (24.68 +/- 0.26 h). We developed a mathematical model comprising 2 coupled circadian oscillators that was tested experimentally with different CJL schedules. Our simulations suggested that under CJL, the system behaves as if it were under a zeitgeber with a period determined by (24 - [phase shift size/days between shifts]). Desynchronization within the system arises according to whether this effective zeitgeber is inside or outside the range of entrainment of the oscillators. In this sense, ChrA(6/2) is interpreted as a (24 - 6/2 = 21 h) zeitgeber, and simulations predicted the behavior of mice under other CJL schedules with an effective 21-hour zeitgeber. Animals studied under an asymmetric T = 21 h zeitgeber (carried out by a 3-hour shortening of every dark phase) showed 2 activity components as observed under ChrA(6/2): an entrained short-period (21.01 +/- 0.03 h) and a long-period component (23.93 +/- 0.31 h). Internal desynchronization was lost when mice were subjected to 9-hour advances every 3 days, a possibility also contemplated by the simulations. Simulations also predicted that desynchronization should be less prevalent under delaying than under advancing CJL. Indeed, most mice subjected to 6-hour delay shifts every 2 days (an effective 27-hour zeitgeber) displayed a single entrained activity component (26.92 +/- 0.11 h). Our results demonstrate that the disruption provoked by CJL schedules is not dependent on the phase-shift magnitude or the frequency of the shifts separately but on the combination of both, through its ratio and additionally on their absolute values. In this study, we present a novel model of forced desynchronization in mice under a specific CJL schedule; in addition, our model provides theoretical tools for the evaluation of circadian disruption under CJL conditions that are currently used in circadian research. PMID- 22306975 TI - Human nonvisual responses to simultaneous presentation of blue and red monochromatic light. AB - Blue light sensitivity of melatonin suppression and subjective mood and alertness responses in humans is recognized as being melanopsin based. Observations that long-wavelength (red) light can potentiate responses to subsequent short wavelength (blue) light have been attributed to the bistable nature of melanopsin whereby it forms stable associations with both 11-cis and all-trans isoforms of retinaldehyde and uses light to transition between these states. The current study examined the effect of concurrent administration of blue and red monochromatic light, as would occur in real-world white light, on acute melatonin suppression and subjective mood and alertness responses in humans. Young healthy men (18-35 years; n = 21) were studied in highly controlled laboratory sessions that included an individually timed 30-min light stimulus of blue (lambda(max) 479 nm) or red (lambda(max) 627 nm) monochromatic light at varying intensities (10(13)-10(14) photons/cm(2)/sec) presented, either alone or in combination, in a within-subject randomized design. Plasma melatonin levels and subjective mood and alertness were assessed at regular intervals relative to the light stimulus. Subjective alertness levels were elevated after light onset irrespective of light wavelength or irradiance. For melatonin suppression, a significant irradiance response was observed with blue light. Co-administration of red light, at any of the irradiances tested, did not significantly alter the response to blue light alone. Under the current experimental conditions, the primary determinant of the melatonin suppression response was the irradiance of blue 479 nm light, and this was unaffected by simultaneous red light administration. PMID- 22306976 TI - Transcription-based oscillator model for light-induced splitting as antiphase circadian gene expression in the suprachiasmatic nuclei. AB - Daily locomotor patterns of a variety of organisms have been interpreted as driven by dual circadian oscillators. Yet, in mammals, cellular data have revealed many circadian oscillators in the bilateral suprachiasmatic nucleus (SCN). To test how large numbers of oscillators could respond to environmental cues as a pair of oscillators, the authors developed a computational model composed of 2 groups of oscillators with strong local interactions and with weaker coupling between the 2 groups. Unlike previous models that assumed that light affects the timing or polarity of coupling between a pair of oscillators, this simulation assumed that light increased the transcription rate of a clock gene and consequently altered circadian properties of individual cells. In constant dark, weak local (within each of the 2 groups) and distant (between group) coupling established in-phase oscillations and a typical single bout of daily activity. In constant light, local synchrony developed only if coupling was strong and resulted in antiphase synchrony between the 2 groups and bimodal daily activity reminiscent of split behavior. These numerical simulations thus showed that splitting behavior can develop with increased light intensity without structural changes in the coupling topology or sign. Instead, the authors propose that light changes intrinsic oscillator properties through the increase of maximal transcription rate of a clock gene, so that as light intensity increases, the output of the coupled network transitions from a single bout of activity through irregular beating to 2 bouts and, in bright constant light, arrhythmicity. PMID- 22306977 TI - Exploring sleepiness and entrainment on permanent shift schedules in a physiologically based model. AB - The effects of permanent shift work on entrainment and sleepiness are examined using a mathematical model that combines a model of sleep-wake switch in the brain with a model of the human circadian pacemaker entrained by light and nonphotic inputs. The model is applied to 8-hour permanent shift schedules to understand the basic mechanisms underlying changes of entrainment and sleepiness. Average sleepiness is shown to increase during the first days on the night and evening schedules, that is, shift start times between 0000 to 0700 h and 1500 to 2200 h, respectively. After the initial increase, sleepiness decreases and stabilizes via circadian re-entrainment to the cues provided by the shifts. The increase in sleepiness until entrainment is achieved is strongly correlated with the phase difference between a circadian oscillator entrained to the ambient light and one entrained to the shift schedule. The higher this phase difference, the larger the initial increase in sleepiness. When entrainment is achieved, sleepiness stabilizes and is the same for different shift onsets within the night or evening schedules. The simulations reveal the presence of a critical shift onset around 2300 h that separates schedules, leading to phase advance (night shifts) and phase delay (evening shifts) of the circadian pacemaker. Shifts starting around this time take longest to entrain and are expected to be the worst for long-term sleepiness and well-being of the workers. Surprisingly, we have found that the circadian pacemaker entrains faster to night schedules than to evening ones. This is explained by the longer photoperiod on night schedules compared to evening. In practice, this phenomenon is difficult to see due to days off on which workers switch to free sleep-wake activity. With weekends, the model predicts that entrainment is never achieved on evening and night schedules unless the workers follow the same sleep routine during weekends as during work days. Overall, the model supports experimental observations, providing new insights into the mechanisms and allowing the examination of conditions that are not accessible experimentally. PMID- 22306978 TI - Electrochemical synthesis and one step modification of PMProDot nanotubes and their enhanced electrochemical properties. AB - Poly (3,4-(2-methylene)propylenedioxythiophene) (PMProDot) nanotubes were synthesized within the pores of polycarbonate and were further modified with styrene and vinylcarbazole by a one step electrochemical method through the methylene functional group. The enhanced electrochemical and electrochromic properties of composite nanotubes were investigated using FTIR, UV/Vis absorbance spectroscopy, and AFM. PMID- 22306979 TI - The conundrum of smoking cessation and weight gain. PMID- 22306980 TI - Do lifestyle behaviours explain socioeconomic differences in all-cause mortality, and fatal and non-fatal cardiovascular events? Evidence from middle aged men in France and Northern Ireland in the PRIME Study. AB - OBJECTIVE: To examine the contribution of lifestyle behaviours to the socioeconomic gradient in all-cause mortality, and fatal and non-fatal cardiovascular events. METHOD: 10,600 men aged 50-59 years examined in 1991-1994 in Northern Ireland (NI) and France and followed annually for deaths and cardiovascular events for 10 years. Baseline smoking habit, physical activity, and fruit, vegetable, and alcohol consumption were assessed. RESULTS: All lifestyle behaviours showed marked socioeconomic gradients for most indicators in NI and France, with the exception of percentage of alcohol consumers in NI and frequency of alcohol consumption in NI and France. At 10 years, there were 544 deaths from any cause and 440 fatal and non-fatal cardiovascular events. After adjustment for country and age, socioeconomic gradients were further adjusted for lifestyle behaviours. For total mortality, the median residual contribution of lifestyle behaviours was 28% and for cardiovascular incidence, 41%. When cardiovascular risk factors were considered in conjunction with lifestyle behaviours these percentages increased to 38% and 67% respectively. CONCLUSION: Lifestyle behaviours contribute to the gradient in mortality and cardiovascular incidence between socioeconomic groups, particularly for cardiovascular incidence, but a substantial proportion of these differentials was not explained by lifestyle behaviours and cardiovascular risk factors. PMID- 22306981 TI - N-methyl N-nitroso Urea induced altered DNA structure initiate hepatocarcinogenesis. AB - The status of inflammatory cytokines IL-1beta, IL-6, the anti-apoptotic gene Bcl2 and key transcription factor NFkappaB in hepatic milieu of N-methyl N-nitroso Urea (MNU) primed Balb/c mice was assessed using RT-PCR and Western blot. Haematoxyline & Eosin (H&E) based histology was performed to evaluate the morphological changes in the cancerous liver cells in respect to control. Laser spectroscopy was used to study the alteration in DNA structure. 40 week MNU treatment induced increased expressions of inflammatory cytokines (IL-1beta, IL 6) of Bcl-2 at mRNA level and NFkappaB and IL-1beta at protein level. Alteration in hepatocytes was clearly demonstrated in H&E stained liver sections compared to control. MNU primed liver DNA samples revealed an interference of MNU in nucleic acid bases and structure, reflected by a peak shift at 1456 cm(-1) and shoulder formation at 1357 cm(-1) compared to control DNA samples. This study emphasizes that MNU, a harmful industrial and environmental pollutant, potentially activates inflammatory cytokines (IL-1beta, IL-6) in hepatic cells with increased expression of NFkappaB which might be responsible for hepatocarcinogenesis in Balb/c mice. The outcome sets the basis for further studies on the mitigating effects of dietary biofactors on MNU. PMID- 22306989 TI - ApoA1: mimetic peptide reverses adipocyte dysfunction in vivo and in vitro via an increase in heme oxygenase (HO-1) and Wnt10b. AB - Insulin resistance is a risk factor in the development of type 2 diabetes and is a major cause of atherosclerosis. Reduction in heme oxygenase (HO-1) has been shown to exacerbate vascular dysfunction and insulin resistance in obese mice and involves a decrease in adiponectin levels. Adiponectin is released from mesenchymal stem cell (MSC)-derived adipocytes, its levels are decreased in type 2 diabetes. We hypothesized that the apoA1 mimetic peptide, L-4F, will target the expression of the HO-1-adiponectin axis and reverse adipocyte dysfunction both in vivo and in vitro. The administration of L-4F [2 mg/Kg/daily (i.p.) for 4-week to 8-week-old obese (ob) mice restored adipocyte function, increased adiponectin release (p < 0.05) and decreased the levels of IL-1 and IL-6 (p < 0.05)]. These perturbations were associated with an increase in insulin sensitivity (p < 0.01 vs. untreated ob mice) and decreased glucose levels (309 + 42 vs. 201 + 8 mg/d after L-4F treatment). Treatment of both mesenchymal stem cell (MSC)-derived adipocytes with L-4F (50 MUg/ml) increased adiponectin (p < 0.05), decreased IL-1 and IL-6 (p < 0.05) levels and increased MSC-derived adipocyte cell numbers by 50% in S phase (p < 0.05). MSC-derived adipocytes treated with L-4F increased WNT10b and decreased Peg 1/Mest. Inhibition of HO activity reversed the decrease in the adipogenic response gene, Peg 1/Mest. An increase of HO-1 expression by L 4F increased insulin-receptor phosphorylation. These findings support the hypothesis that L-4F increases early adipocyte markers, HO-1-adiponectin, WNT10b and decreases Peg1/Mest, negative regulators of adipocyte differentiation. PMID- 22306997 TI - BRCA1-directed, enhanced and aberrant homologous recombination: mechanism and potential treatment strategies. AB - Despite intense studies, questions still remain regarding the molecular mechanisms leading to the development of hereditary breast and ovarian cancers. Research focused on elucidating the role of the breast cancer susceptibility gene 1 (BRCA1) in the DNA damage response may be of the most critical importance to understanding these processes. The BRCA1 protein has an N-terminal RING domain possessing E3 ubiquitinligase activity and a C-terminal BRCT domain involved in binding specific phosphoproteins. These domains are involved directly or indirectly in DNA double-strand break (DSB) repair. As the two terminal domains of BRCA1 represent two separate entities, understanding how these domains communicate and are functionally altered in regards to DSB repair is critical for understanding the development of BRCA1-related breast and ovarian cancers and for developing novel therapeutics. Herein, we review recent findings of how altered functions of these domains might lead to cancer through a mechanism of increased aberrant homologous recombination and possible implications for the development of BRCA1 inhibitors. PMID- 22306998 TI - Novel E3 ligase component FBXL7 ubiquitinates and degrades Aurora A, causing mitotic arrest. AB - Aurora family kinases play pivotal roles in several steps during mitosis. Specifically, Aurora A kinase is an important regulator of bipolar mitotic spindle formation and chromosome segregation. Like other members of the Aurora family, Aurora A kinase is also regulated by post-translational modifications. Here, we show that a previously undescribed E3 ligase component belonging to the SCF (Skp-Cullin1-F-box protein) E3 ligase family, SCFFBXL7, impairs cell proliferation by mediating Aurora A polyubiquitination and degradation. Both Aurora A and FBXL7 co-localize within the centrosome during spindle formation. FBXL7 ectopic expression led to G(2)/M phase arrest in transformed epithelia, resulting in the appearance of tetraploidy and mitotic arrest with circular monopolar spindles and multipolar spindle formation. Interestingly, FBXL7 specifically interacts with Aurora A during mitosis but not in interphase, suggesting a regulatory role for FBXL7 in controlling Aurora A abundance during mitosis. PMID- 22307005 TI - Endosulfan and flutamide impair testicular development in the juvenile Asian catfish, Clarias batrachus. AB - Endosulfan and flutamide, a widely used pesticide and a prostate cancer/infertility drug, respectively, have an increased risk of causing endocrine disruption if they reach water bodies. Though many studies are available on neurotoxicity/bioaccumulation of endosulfan and receptor antagonism of flutamide, only little is known about their impact on testicular steroidogenesis at molecular level. Sex steroids play an important role in sex differentiation of lower vertebrates including fishes. Hence, a small change in their levels caused by endocrine disruptors affects the gonadal development of aquatic vertebrates significantly. The aim of this study was to evaluate the effects of endosulfan and flutamide on testis-related transcription factor and steroidogenic enzyme genes with a comparison on the levels of androgens during critical period of catfish testicular development. We also analyzed the correlation between the above-mentioned genes and catfish gonadotropin-releasing hormone (cfGnRH)-tryptophan hydroxylase2 (tph2). The Asian catfish, Clarias batrachus males at 50 days post hatch (dph) were exposed to very low dose of endosulfan (2.5 MUg/L) and flutamide (33 MUg/L), alone and in combination for 50 days. The doses used in this study were far less than those used in the previous studies of flutamide and reported levels of endosulfan in surface water and sediments. Sampling was done at end of the treatments (100 dph) to perform testicular germ cell count (histology), measurements of testosterone (T) and 11 ketotestosterone (11-KT) by enzyme immunoassay and transcript quantification by quantitative real-time PCR. In general, treatments decreased the expression of several genes including testis-related transcription factors (dmrt1, sox9a and wt1), steroidogenic enzymes (11beta-hsd2, 17beta-hsd12 and P450c17), steroidogenic acute regulatory protein and orphan nuclear receptors (nr2c1 and Ad4BP/SF-1). In contrast, the transcripts of cfGnRH and tph2 were elevated in the brain of all treated groups with maximum elevation in the endosulfan group. However, combination of endosulfan and flutamide (E+F) treatment showed minor antagonism in a few results of transcript quantification. Levels of T and 11-KT were elevated after flutamide and E+F treatments while no change was seen in the endosulfan group signifying the effect of flutamide as an androgen receptor antagonist. All the treatments modulated testis growth by decreasing the progression of differentiation of spermatogonia to spermatocytes. Based on these results, we suggest that the exposure to endosulfan and flutamide, even at low doses, impairs testicular development either directly or indirectly at the level of brain. PMID- 22307006 TI - Bioconcentration and metabolism of decabromodiphenyl ether (BDE-209) result in thyroid endocrine disruption in zebrafish larvae. AB - Polybrominated diphenyl ethers (PBDEs) have the potential to disturb the thyroid endocrine system, but little is known of such effects or underlying mechanisms of BDE-209 in fish. In the present study, bioconcentration and metabolism of BDE-209 were investigated in zebrafish embryos exposed at concentrations of 0, 0.08, 0.38 and 1.92 mg/L in water until 14 days post-fertilization (dpf). Chemical analysis revealed that BDE-209 was accumulated in zebrafish larvae, while also metabolic products were detected, including octa- and nona-BDEs, with nona-BDEs being predominant. The exposure resulted in alterations of both triiodothyronine (T3) and thyroxine (T4) levels, indicating thyroid endocrine disruption. Gene transcription in the hypothalamic-pituitary-thyroid (HPT) axis was further examined, and the results showed that the genes encoding corticotrophin-releasing hormone (CRH) and thyroid-stimulating hormone (TSHbeta) were transcriptionally significantly up-regulated. Genes involved in thyroid development (Pax8 and Nkx2.1) and synthesis (sodium/iodide symporter, NIS, thyroglobulin, TG) were also transcriptionally up-regulated. Up-regulation of mRNA for thyronine deiodinase (Dio1 and Dio2) and thyroid hormone receptors (TRalpha and TRbeta) was also observed. However, the genes encoding proteins involved in TH transport (transthyretin, TTR) and metabolism (uridinediphosphate-glucuronosyl-transferase, UGT1ab) were transcriptionally significantly down-regulated. Furthermore, protein synthesis of TG was significantly up-regulated, while that of TTR was significantly reduced. These results suggest that the hypothalamic-pituitary thyroid axis can be evaluated to determine thyroid endocrine disruption by BDE 209 in developing zebrafish larvae. PMID- 22307007 TI - Reproductive and histopathological effects in wild fish inhabiting an effluent dominated stream, Wascana Creek, SK, Canada. AB - During the winter low flow periods, Wascana Creek, Saskatchewan, Canada, can be 100% treated municipal wastewater downstream of the City of Regina's Wastewater Treatment Plant. The objective of this study was to determine if exposure to municipal effluent affects the health and reproductive development of fish in an effluent-dominated stream. Field studies were conducted on post-spawning (August 2006), spawning (June 2007), recrudescent (October 2007) and pre-spawning (May 2008) sentinel fish [Fathead Minnow Pimephales promelas and Brook Stickleback Culaea inconstans] to assess responses in terms of growth (condition factor), reproduction (in vitro sex steroid biosynthetic capacity, and gonadosomatic indices, histology) and survival associated with the effluent outfall. Sentinel species demonstrated varying responses depending on the season of field collections. While Stickleback collected downstream of the sewage discharge were often longer, heavier and had greater condition, Fatheads from the same site were shorter and lighter. Exposed fish of both species exhibited delayed spawning and altered gonadal development depending on the season. Exposed male Fathead Minnows also had significantly lower scores of secondary sexual characteristics (fewer nuptial tubercles, little or no development of the dorsal pad, and the lack of presence of a dorsal fin dot). Histopathology of exposed Fathead Minnows revealed thickening of the gill lamellae and alterations in structure of the kidneys (inflammation of the proximal tubules and Bowman's capsule). It is not known if the effluents are affecting natural reproduction and recruitment into this population or if these impacted populations rely on immigration from upstream reaches to sustain the populations. Climate change and human population growth will further challenge this effluent-dominated stream's ability to assimilate nutrients and contaminants which may further impair the performance of fish in this arid environment. PMID- 22307008 TI - Tumor vasculature as a therapeutic target in non-small cell lung cancer. AB - INTRODUCTION: We aim to describe the molecular mechanisms relevant to angiogenesis inhibition and to critically evaluate the current evidence for the use of angiogenic inhibitors (AIs) in the treatment of non-small cell lung cancer (NSCLC). METHODS: The literature on the basic concepts of tumor angiogenesis is reviewed. Published articles and major lung cancer conference abstracts were screened for reports on the use of AI in NSCLC patients and the National Institutes of Health clinical trials database was searched for relevant ongoing studies. RESULTS: We delineate in this review the molecular and cellular aspects of angiogenesis and vasculogenesis and outline the relevance of these to lung cancer. Clinical studies of AIs in NSCLC reported to date as well ongoing studies are summarized. Major issues discussed include the choice of the right molecular target; characteristics of various tyrosine kinase inhibitors; potential drawbacks and concerns regarding the application of AIs in clinical practice, and major unanswered questions and future directions. CONCLUSIONS: AIs have antitumor activity in NSCLC and have become part of the standard of care for patients with advanced nonsquamous cell carcinoma. Unfortunately, the gains have been modest and robust predictive biomarkers are urgently needed. Clinical trials to date have validated the tumor vasculature as a legitimate target, and as our understanding of the biology of tumor angiogenesis increases, exciting new therapeutic approaches are being explored. PMID- 22307009 TI - p95HER2 truncated form in resected non-small cell lung cancer. AB - INTRODUCTION: Recent studies suggested that p95HER2, the NH2-terminally truncated form of human epidermal growth factor receptor 2 (HER2), could confer resistance to monoclonal antibodies against HER2 (HER2-mab). The aim of this study was to investigate the role of p95HER2 according to HER2 gene copy number (GCN) and HER2 mutation in non-small cell lung cancer (NSCLC). METHODS: The study included 447 resected NSCLC patients evaluated for P95HER2 status by immunofluorescence. Data were correlated with HER2 GCN evaluated by fluorescence in situ hybridization (FISH) and HER2 mutations. Tumors were scored as positive for p95HER2 expression if any cytoplasmic staining was detected. RESULTS: P95HER2 was successfully evaluated in 431 patients and was positive (p95HER2+) in 33 (7.6%) cases. HER2 GCN was evaluable in 439 patients, and increased GCN (at least four copies in at least 40% cells) was found in 60 cases, of which 22 (5.0%) displayed gene amplification (GA). Among the 22 patients with HER2 amplification, only one resulted P95HER2+. To further investigate whether the receptor is truncated in presence of gene mutation, in addition to the study cohort, we analyzed p95HER2 status in eight NSCLC samples harboring HER2 mutation, and only one case resulted p95HER2+. In the whole population, p95HER2- patients had numerically higher risk of death than p95HER2+ (hazard ratio = 1.4, p = 0.2). No difference in survival was observed between patients with or without HER2 GA (median 38 versus 41 months, p = 0.46). HER2 GA was significantly associated with EGFR and MET GA, with no effect on survival. CONCLUSIONS: HER2 truncation and HER2 increased GCN are not prognostic in resected NSCLC. P95HER2 is a very rare event in individuals displaying HER2 gene amplification or mutation. PMID- 22307010 TI - Pleural fluid cytological yield and visceral pleural invasion in patients with epithelioid malignant pleural mesothelioma. AB - INTRODUCTION: Malignant pleural mesothelioma (MPM) is an aggressive malignancy arising from mesothelial cells lining the pleura. Most commonly, it presents as a unilateral pleural effusion. MPM usually develops on the parietal pleural surface and later spreads to the visceral pleura. Visceral pleural involvement entails a more advanced disease stage and is therefore an important prognostic factor. Pleural fluid (PF) cytology is often the first diagnostic test, but the sensitivity in the literature varies from 4 to 77%. However, no data are available for the diagnostic yield of cytological PF analysis with regard to the visceral pleural involvement. The aim of this study is to assess whether PF cytological yield is related to the extent and pattern of visceral pleural invasion, as assessed by thoracoscopy. METHODS: Medical records of all patients who underwent thoracoscopy for suspicion of malignant pleural effusion from two hospitals were reviewed. Patients were selected if they initially underwent a diagnostic thoracentesis before thoracoscopy, if visceral pleural appearance during thoracoscopy was clearly documented, and MPM confirmed on pleural tissue biopsy. RESULTS: Seventy-five patients were selected. Forty-five patients had a positive PF cytology on thoracentesis, while 30 had a negative PF cytology. Thoracoscopy showed parietal pleural invasion in all subjects. Interestingly, 82% of patients with positive PF cytology on thoracentesis had visceral pleural involvement, whereas only 30% of those with negative PF cytology had visceral pleural invasion. The pattern of visceral pleural invasion consisted of pleural masses, nodules, or pleural thickening. A multivariate regression identified visceral pleural invasion (p < 0.001) as the only independent factor predicting the positivity of cytology on pleural effusion. CONCLUSION: In epithelioid MPM, PF cytological yield was significantly higher in patients with visceral pleural invasion assessed by thoracoscopy. Positive PF cytology is associated with a more advanced disease. PMID- 22307011 TI - Inflammation-based prognostic indices in malignant pleural mesothelioma. AB - INTRODUCTION: Chronic inflammation plays a key role in the pathogenesis of malignant pleural mesothelioma (MPM) as a result of asbestos exposure. Biomarkers of systemic inflammation have been shown to predict the natural history of MPM; however, this observation lacks independent validation. Our aim was to compare the prognostic performance of three inflammation-based biomarkers in predicting overall survival (OS) in MPM. METHODS: In patients with histologically proven MPM, the inflammation-based prognostic scores modified Glasgow Prognostic Score (mGPS), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio were studied and compared with the European Organization for the Research and Treatment of Cancer Prognostic Score (EPS) and other known potential prognostic factors such as gender, histologic subtype, Eastern Cooperative Oncology Group performance status, and baseline blood parameters. RESULTS: A total of 171 MPM patients presenting to Imperial College NHS Trust were studied. In univariate analyses, the following parameters were predictors of OS: female gender (p = 0.03), epithelioid histology (p = 0.03), normal C-reactive protein (p = 0.03), baseline white blood cell count <8.3 * 10/liter (p = 0.04), EPS (p = 0.003), mGPS (p < 0.001), NLR (p = 0.006), and platelet-to-lymphocyte ratio (p = 0.03). Multivariate survival analysis confirmed the mGPS (hazard ratio = 2.6; p < 0.001) and NLR (hazard ratio = 2.0; p = 0.008), but not the EPS, as independent predictors of OS. Tissue expression of Ki-67 (p < 0.001) and vascular endothelial growth factor (p < 0.001) was higher in a subgroup of patients with high-risk inflammatory scores. CONCLUSIONS: The mGPS and NLR are externally validated prognostic indices in patients with MPM and correlate with sustained neoangiogenesis and increased proliferative index. PMID- 22307012 TI - Adjuvant chemotherapy for non-small cell lung cancer: practice patterns and outcomes in the general population of Ontario, Canada. AB - BACKGROUND: Adjuvant chemotherapy (ACT) is known to improve survival in patients with early-stage non-small cell lung cancer. Herein, we describe chemotherapy regimens used, dose modifications, survival, and treatment-related toxicity in the general population. METHODS: All cases of non-small cell lung cancer diagnosed in Ontario in the period 2004-2006 who underwent surgical resection (n = 3354) were identified using the Ontario Cancer Registry in this population based retrospective cohort study. We linked electronic records of treatment to the registry to identify all cases treated with ACT (n = 1032) and describe drugs, regimens, and dosages delivered. As a proxy measure of ACT-related toxicity, we evaluated deaths and hospitalizations within 16 weeks of starting ACT. Factors associated with dose modification were evaluated by logistic regression. The Cox proportional hazards model was used to describe associations between patient-, disease-, and treatment-related factors and survival. RESULTS: ACT regimens were identified for 584 of 1032 ACT cases. Almost all cases included cisplatin- or carboplatin-based regimens (478/584, 82%, and 99/584, 17%, respectively). The most common regimen was a vinroelbine/cisplatin doublet (412/584, 71%); 64% of these cases had a dose reduction or omission. Dose modification was not associated with inferior survival on multivariate analysis. Twelve percent of all ACT cases were admitted to hospital within 16 weeks of starting ACT, and there was a 1.6% death rate potentially attributable to ACT. Survival of all ACT cases was comparable with outcomes reported in clinical trials. CONCLUSIONS: ACT regimens used, toxicity, and survival outcomes in the general population are comparable with those reported in clinical trials. Dose modifications used in clinical practice are not associated with inferior survival. PMID- 22307013 TI - Single-institution, multidisciplinary experience with surgical resection of primary chest wall sarcomas. AB - INTRODUCTION: Primary chest wall sarcomas are rare mesenchymal tumors and their mainstay of therapy is wide surgical resection. We report our single-institution, multidisciplinary experience with full-thickness resection for primary chest wall sarcomas. METHODS: A retrospective review of our prospectively maintained databases revealed that 51 patients were referred for primary chest wall sarcomas from 1990 to 2009. RESULTS: All patients required resections that included rib and/or sternum. Twenty-nine patients (57%) had extended resections beyond the chest wall. Forty-two patients (82%) required prosthetic reconstruction and 17 patients (33%) had muscle flap coverage. Overall, 51% (26/51) of patients received neoadjuvant therapy. Seventy-three percent (11/15) of high-grade soft tissue sarcomas, 77% (10/13) of high-risk bony sarcomas, and 67% (4/6) of desmoid tumors were treated with induction therapy. Negative margins were obtained in 46 patients (90%). There were no perioperative mortalities. Eight patients (16%) experienced complications. Local recurrence and metastasis was detected in 14 and 23%. Five-year overall and disease-free survivals were 66% and 47%, respectively. Favorable prognostic variables for survival included age <=50 years, tumor volume <=200 cm, desmoid tumor, bony tumor, chondrosarcoma, and low-grade soft tissue sarcoma. CONCLUSIONS: We report our multidisciplinary experience with primary chest wall sarcomas that included induction therapy in the majority of high-risk soft tissue and bony sarcomas and desmoid tumors. Despite aggressive preoperative treatments, acceptable surgical results with low morbidity and mortality can be achieved. Neoadjuvant systemic therapy may reduce local and distant recurrence and improve overall survival. PMID- 22307014 TI - Understanding the different activities of highly promiscuous MbtI by computational methods. AB - Salicylate synthase from Mycobacterium tuberculosis, MbtI, is a highly promiscuous Mg(2+) dependent enzyme with up to four distinct activities detected in vitro: isochorismate synthase (IS), isochorismate pyruvate lyase (IPL), salicylate synthase (SS) and chorismate mutase (CM). In this paper, Molecular Dynamic (MD) simulations employing hybrid quantum mechanics/molecular mechanics (QM/MM) potentials have been carried out to get a detailed knowledge of the IS and the IPL activities at the molecular level. According to our simulations, the architecture of the MbtI active site allows catalyzing the two reactions: the isochorismate formation, by means of a stepwise mechanism, and the salicylate production from isochorismate, that appears to be pericyclic in nature. Findings also explain the role of the magnesium cation and the pH dependence activity experimentally observed in MbtI. Mg(2+) would be polarizing and pre-organizing the substrate and active site, as well as shifting the pK(a) values of key active site residues. PMID- 22307016 TI - The increase from 2.5 to 5 mg/kg of rabbit anti-thymocyte-globulin dose in reduced intensity conditioning reduces acute and chronic GVHD for patients with myeloid malignancies undergoing allo-SCT. AB - We previously reported that reduced intensity conditioning (RIC) regimen with fludarabine, BU and 2.5 mg/kg of rabbit anti-thymocyte globulin (r-ATG) was effective but associated with a high rate of acute and chronic GVHD. Therefore, we increased the dose of r-ATG to 5 mg/kg. In this report, we analyzed 87 patients with AML or myelodysplastic syndrome (MDS) undergoing allo-SCT from an HLA-identical sibling donor from 2000 to 2010. RIC consisted of fludarabine, BU and r-ATG 2.5 mg/kg on 1 day (r-ATG1; n=53) or 2.5 mg/kg per day over 2 days (r ATG2; n=22). Grade 2-4 acute GVHD incidence at day 100 was 30.2% and 8.8% in the r-ATG1 and r-ATG2 groups, respectively (P=0.038). Extensive chronic GVHD incidence was 60.4% and 12% in the r-ATG1 and r-ATG2 groups, respectively (P<0.001). The relapse incidences (RI) at 24 months were 18.9% and 28.5% in r ATG1 and r-ATG2 groups, respectively (P=0.640). Overall and PFS were not different between the r-ATG1 and r-ATG2 groups. r-ATG dose at 5 mg/kg in the setting of RIC seems a good balance allowing GVHD prevention and antitumor effect with a remarkable reduction of GVHD incidence without an identical level of increased relapse rate. PMID- 22307017 TI - Fecal calprotectin in allogeneic stem cell transplantation for the diagnosis of acute intestinal graft versus host disease. PMID- 22307018 TI - High-dose corticosteroids with or without etanercept for the treatment of idiopathic pneumonia syndrome after allo-SCT. AB - Idiopathic Pneumonia Syndrome (IPS) is a common complication after allo-SCT and results in high mortality rates. Conventional treatment for IPS typically includes supportive care and high-dose corticosteroids (CS). Data suggests that TNF-alpha is important in the pathogenesis of IPS and that the TNF-alpha inhibitor etanercept may be useful for IPS treatment. We performed a retrospective comparison of consecutive patients treated at our center for IPS with CS only from 1999 to 2003 (group 1, n=22) or CS plus etanercept from 2004 to 2007 (group 2, n=17). In all, 18% of patients in group 1 vs 53% in group 2 were successfully taken off respiratory support and discharged from the hospital (P=0.039). OS was significantly better for recipients of CS plus etanercept (P=0.003). The estimated survival at 28 days and 2 years after IPS was 36.4% (95% CI 17-56%) and 9.1% (95% CI 2-25%) for group 1 and 88.2% (95% CI 61-97%) and 18% (95% CI 4-38%) for group 2, respectively. Our retrospective comparison suggests that the addition of etanercept to CS for IPS improves response rates and OS. However, outcomes remain limited in both groups, highlighting the need for more effective interventions to treat early and late complications of IPS. PMID- 22307019 TI - Characterization of SfPgdA, a Shigella flexneri peptidoglycan deacetylase required for bacterial persistence within polymorphonuclear neutrophils. AB - Peptidoglycan deacetylases protect the Gram-positive bacteria cell wall from host lysozymes by deacetylating peptidoglycan. Sequence analysis of the genome of Shigella flexneri predicts a putative polysaccharide deacetylase encoded by the plasmidic gene orf185, renamed here SfpgdA. We demonstrated a peptidoglycan deacetylase (PGD) activity with the purified SfPgdA in vitro. To investigate the role SfPgdA in virulence, we constructed a SfpgdA mutant and studied its phenotype in vitro. The mutant showed an increased sensitivity to lysozyme compared to the parental strain. Moreover, the mutant was rapidly killed by polymorphonuclear neutrophils (PMNs). Specific substitution of histidines residues 120 and 125, located within the PGD catalytic domain, by phenylalanine abolished SfPgdA function. SfPgdA expression is controlled by PhoP. Mutation of phoP increases sensitivity to lysozyme compared to the SfpgdA mutant. Here, we confirmed that SfPgdA expression is enhanced under low magnesium concentration and not produced by the phoP mutant. Ectopic expression of SfPgdA in the phoP mutant restored lysozyme resistance and parental bacterial persistence within PMNs. Together our results indicate that PG deacetylation mechanism likely contributes to Shigella persistence by subverting detection by the host immune system. PMID- 22307020 TI - Regioselective zincation of indazoles using TMP2Zn and Negishi cross-coupling with aryl and heteroaryl iodides. AB - The metalation of various SEM-protected functionalized indazoles with TMP(2)Zn provides 3-zincated indazoles which undergo palladium-catalyzed Negishi cross couplings in good yields. PMID- 22307021 TI - Dicarba-closo-dodecarborane-containing half-sandwich complexes of ruthenium, osmium, rhodium and iridium: biological relevance and synthetic strategies. AB - This review describes how the incorporation of dicarba-closo-dodecarboranes into half-sandwich complexes of ruthenium, osmium, rhodium and iridium might lead to the development of a new class of compounds with applications in medicine. Such a combination not only has unexplored potential in traditional areas such as Boron Neutron Capture Therapy agents, but also as pharmacophores for the targeting of biologically important proteins and the development of targeted drugs. The synthetic pathways used for the syntheses of dicarba-closo-dodecarboranes containing half-sandwich complexes of ruthenium, osmium, rhodium and iridium are also reviewed. Complexes with a wide variety of geometries and characteristics can be prepared. Examples of addition reactions on the metal centre, B-H activation, transmetalation reactions and/or direct formation of metal-metal bonds are discussed (103 references). PMID- 22307022 TI - The experience of living at home with frailty in old age: a psychosocial qualitative study. AB - BACKGROUND: With enhanced longevity, many people in late old age find themselves frail and living at home, often alone. Whilst conceptualisations vary, frailty is often used in clinical practice as a directional term, to refer to older people at particular risk of adverse health outcomes and to organise care. Investigation of the experience of being frail is a complementary and necessary addition to international research endeavours clearly to define, predict and measure frailty. Currently, there is little empirical work exploring how people over time manage being frail. OBJECTIVE: The study aimed to understand the experience over time of home-dwelling older people deemed frail, in order to enhance the evidence base for person-centred approaches to frail elder care. DESIGN: The study design combined psychosocial narrative approaches and psycho-dynamically informed observation. Data on the experience of 15 frail older people were collected by visiting them up to four times over 17 months. These data were analyzed using psychosocial analytical methods that combined case based in-depth staged analysis of narratives with psycho-dynamically informed interpretations of observational data. SETTING: The study was carried out in the homes of the participants; all lived in a socio-economically diverse area of inner London. PARTICIPANTS: 15 participants were purposively selected for living at home, being aged 85 or older and regarded as frail by a clinical multi-disciplinary intermediate care team. RESULTS: The findings challenge the negative terms in which frailty in older age is viewed in the predominant models. Rather, frailty is understood in terms of potential capacity - a state of imbalance in which people experience accumulated losses whilst working to sustain and perhaps create new connections. CONCLUSION: This study suggests that holding together loss and creativity is the ordinary, but nonetheless remarkable, experience of frail older people. For frail older people, the presence of others to engage with their stories, to recognise and value the daily rituals that anchor their experience and to facilitate creative connections is vital if they are to retain capacity and quality of life whilst being frail. PMID- 22307023 TI - A cross-sectional analysis of patterns of obesity in a cohort of working nurses and midwives in Australia, New Zealand, and the United Kingdom. AB - OBJECTIVE: The aim of this study was to examine the prevalence of overweight and obesity and the association with demographic, reproductive work variables in a representative cohort of working nurses and midwives. DESIGN: A cross sectional study of self reported survey data. SETTINGS: Australia, New Zealand and the United Kingdom. METHODS: Measurement outcomes included BMI categories, demographic (age, gender, marital status, ethnicity), reproductive (parity, number of births, mother's age at first birth, birth type and menopausal status) and workforce (registration council, employment type and principal specialty) variables. PARTICIPANTS: 4996 respondents to the Nurses and Midwives e-Cohort study who were currently registered and working in nursing or midwifery in Australia (n=3144), New Zealand (n=778) or the United Kingdom (n=1074). RESULTS: Amongst the sample 61.87% were outside the healthy weight range and across all three jurisdictions the prevalence of obesity in nurses and midwives exceeded rates in the source populations by 1.73% up to 3.74%. Being overweight or obese was significantly associated with increasing age (35-44 yrs aOR 1.71, 95% CI 1.41 2.08; 45-55 yrs aOR 1.90, 95%CI 1.56-2.31; 55-64 aOR 2.22, 95% CI 1.71-2.88), and male gender (aOR 1.46, 95% CI 1.15-1.87). Primiparous nurses and midwives were more likely to be overweight or obese (aOR 1.37, 95% CI 1.06-1.76) as were those who had reached menopause (aOR 1.37, 95% CI 1.11-1.69). Nurses and midwives in part-time or casual employment had significantly reduced risk of being overweight or obese, (aOR 0.81, 95% CI 0.70-0.94 and aOR 0.75, 95% CI 0.59-0.96 respectively), whilst working in aged carried increased risk (aOR 1.37, 95% CI 1.04-1.80). CONCLUSION: Nurses and midwives in this study have higher prevalence of obesity and overweight than the general population and those who are older, male, or female primiparous and menopausal have significantly higher risk of overweight or obesity as do those working fulltime, or in aged care. The consequences of overweight and obesity in this occupational group may impact on their workforce participation, their management of overweight and obese patients in their care as well as influencing their individual health behaviours and risks of occupational injury and chronic disease. PMID- 22307024 TI - Long working hours and alcohol risk among Australian and New Zealand nurses and midwives: a cross-sectional study. AB - BACKGROUND: The relationship between long working hours and harmful alcohol consumption reported in the literature is equivocal. OBJECTIVE: This study aimed to investigate this relationship in a methodologically rigorous fashion. DESIGN AND PARTICIPANTS: A cross-sectional analysis of a large cohort study of Australian and New Zealand nurses and midwives was undertaken. METHODS: Psychometrically robust standardised assessments of alcohol consumption and problems and other key variables were elicited using an electronic survey. Crude and adjusted logistic regression models using complete case and multistage multiple imputed data were employed. RESULTS: The study included 4419 participants, 3552 from Australia and 867 from New Zealand. Long working hours were common, with 33.2% working 40-49 h/week and 7.5% working >=50 h/week. Overall, 13.9% engaged in harmful daily drinking. Significant associations between long working hours and harmful daily alcohol consumption was seen in crude and adjusted complete case and imputed logistic regression models. In the adjusted model with imputed data, the odds of harmful daily drinking increased by 1.17 (95% confidence interval: 1.01, 1.36) between <40 h/week and 40-49 h/week groups, and between 40-49 h/week and >=50 h/week groups. CONCLUSIONS: Many nurses and midwives engaging in harmful daily drinking and work long hours. Since the late 1970s, the average hours worked by full-time employees in Australia has increased. Unless these long working hours can be curbed, workforce policies and programmes aimed at prevention, supportive and empathetic intervention, and recovery need to be instigated; both to protect patients and the nurses and midwives themselves. PMID- 22307025 TI - In vivo monitoring of the bone healing process around different titanium alloy implant surfaces placed into fresh extraction sockets. AB - OBJECTIVES: Increasing surface roughness and coating with tricalcium phosphate of titanium and titanium alloy implants has been proposed to provide better rates of osseointegration. However, how these changes in surface topography and chemistry influence the osseointegration process of immediate implants placed in fresh extraction sockets is unclear. This study investigated the influence of three clinically employed implant surfaces on the early bone healing events in vivo. METHODS: Machined smooth implants were milled from grade 5 Ti6Al4V titanium. Surfaces were moderately roughened by grit blasting, which were then coated with tricalcium phosphate. Implants were placed into freshly extracted incisor sockets of mandibles of normal Wistar rats and left for 1, 3 and 9 weeks. Healing bone tissue around the implants was examined by histochemistry and immunocytochemistry to localise PCNA proliferative cells, and osteoblast differentiation markers osteopontin and osteocalcin. Positive synthesising cells were counted using image analysis. RESULTS: Histology indicated no differences in the amount or pattern of bone formation within the healing tissue surrounding the different implant surfaces. Bone healing occurred predominantly on exposed bone surfaces (distance osteogenesis) and not on the implant surface (contact osteogenesis). No differences were observed in the number or timing of PCNA, osteopontin and osteocalcin positive cells within the bone healing tissue around each of the implant analysed. CONCLUSION: For immediately placed implants, the surface modifications investigated appeared to have little influence on the activity of bone forming cells surrounding the implant, probably due to the high level of distance osteogenesis seen within this scenario. CLINICAL SIGNIFICANCE: For immediate placement of implants into fresh extraction sockets, titanium implants with roughened surfaces and coating with tricalcium phosphate have negligible influence in accelerating the early bone healing events of osseointegration. PMID- 22307026 TI - Fluid biopsy for circulating tumor cell identification in patients with early-and late-stage non-small cell lung cancer: a glimpse into lung cancer biology. AB - Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, and recent data suggest a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there are few published data about CTC prevalence rates and morphologic heterogeneity in early-stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging. We investigated CTC counts, morphology and aggregation in early stage, locally advanced and metastatic NSCLC patients by using a fluid-phase biopsy approach that identifies CTCs without relying on surface-receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naive NSCLC patients. 73% of the total population had a positive HD-CTC count (>0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs mL-1 (range 0-515.6) and a mean of 44.7 (+/-95.2) HD CTCs mL-1. No significant difference in the medians of HD-CTC counts was detected between stage IV (n = 31, range 0-178.2), stage III (n = 34, range 0-515.6) and stages I/II (n = 13, range 0-442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD CTC assay shows high sensitivity in the detection and characterization of both early- and late-stage lung cancer CTCs. Extensive studies are warranted to investigate the prognostic value of CTC profiling in early-stage lung cancer. This finding has implications for the design of extensive studies examining screening, therapy and surveillance in lung cancer patients. PMID- 22307027 TI - Highly emissive hand-shaped pi-conjugated alkynylpyrenes: synthesis, structures, and photophysical properties. AB - Three alkynyl-functionalised, hand-shaped, highly fluorescent and stable emitters, namely, 2-tert-butyl-4,5,7,9,10-pentakis(p-R-phenylethynyl)pyrenes have been successfully synthesized via a Pd/Cu-catalysed Sonogashira cross-coupling reaction. The chemical structures of the alkynylpyrenes were fully characterized by their (1)H/(13)C NMR spectra, mass spectroscopy and elemental analysis. Synchrotron single-crystal X-ray analysis revealed that there is a 1-D, slipped, face-to-face motif with off-set, head-to-tail stacked columns, which are clearly influenced by the single, bulky, tert-butyl group in the pyrene ring at the 2 position. Detailed studies on the photophysical properties in both solutions and thin films strongly indicate that they might be promising candidates for optoelectronic applications, such as organic light-emitting devices (OLEDs) or as models for investigating the fluorescent structure-property relationship of the alkynyl-functionalised pyrene derivatives. PMID- 22307028 TI - Osteoclast resorption of thermal spray hydoxyapatite coatings is influenced by surface topography. AB - Coating characteristics such as composition, crystallite features and topography collectively impact the cell response. The influence from splats has not yet been assessed for hydroxyapatite (HAp) thermal spray coatings. The objective of this work is to (a) survey the topography on commercial implants, (b) ascertain topography formation from single splats, and (c) determine the osteoclast resorption pattern on a topographically refined coating compared to dentine. Coatings on dental implants, an orthopedic screw, a femoral stem and a knee implant were studied for reference. The effects of substrate pre-heat, roughness, spray distance and particle size on the coating roughness and topography were studied. Human-derived osteoclasts were placed on a coating with refined topography and compared to dentine, a polished coating and polished sintered HAp. A pre-heat of at least 200 degrees C on titanium was required to form rounded splats. The greatest influence on coating roughness and topography arose from particle size. A 2-fold increase in the mean particle size from 30 to 72 MUm produced a significant difference (P<0.001) in roughness from 4.8 and 9.7 MUm. A model is shown to illustrate topography formation, nanostructure evolution on single splats, and the topography as seen in commercial implants. Osteoclasts showed a clear preference for activity on coatings with refined topography. A one way ANOVA test revealed a significantly greater pit depth (P=0.022) for dentine (14 MUm) compared to the as-sprayed and polished coating (5 MUm). Coatings with topography display a similar number of resorption pits with dentine, but a 10 fold greater number than polished coatings, emphasizing the importance of flattened droplet topography on implant surfaces. PMID- 22307029 TI - Supercritical CO2 fluid-foaming of polymers to increase porosity: a method to improve the mechanical and biocompatibility characteristics for use as a potential alternative to allografts in impaction bone grafting? AB - Disease transmission, availability and cost of allografts have resulted in significant efforts to find an alternative for use in impaction bone grafting (IBG). Recent studies identified two polymers with both structural strength and biocompatibility characteristics as potential replacements. The aim of this study was to assess whether increasing the polymer porosity further enhanced the mechanical and cellular compatibility characteristics for use as an osteogenic biomaterial alternative to allografts in IBG. Solid and porous poly(DL-lactide) (P(DL)LA) and poly(DL-lactide-co-glycolide) (P(DL)LGA) scaffolds were produced via melt processing and supercritical CO(2) foaming, and the differences characterized using scanning electron microscopy (SEM). Mechanical testing included milling and impaction, with comparisons made using a shear testing rig as well as a novel agitation test for cohesion. Cellular compatibility tests for cell number, viability, and osteogenic differentiation using WST-1 assays, fluorostaining, and ALP assays were determined following 14 day culture with skeletal stem cells. SEM showed excellent porosity throughout both of the supercritical-foam-produced polymer scaffolds, with pores between 50 and 200 MUm. Shear testing showed that the porous polymers exceeded the shear strength of allograft controls (P<0.001). Agitation testing showed greater cohesion between the particles of the porous polymers (P<0.05). Cellular studies showed increased cell number, viability, and osteogenic differentiation on the porous polymers compared to solid block polymers (P<0.05). The use of supercritical CO(2) to generate porous polymeric biodegradable scaffolds significantly improves the cellular compatibility and cohesion observed compared to non-porous counterparts, without substantial loss of mechanical shear strength. These improved characteristics are critical for clinical translation as a potential osteogenic composite for use in IBG. PMID- 22307030 TI - Phage biology: T4 to TA, checkmate. PMID- 22307031 TI - Cellular microbiology: an unconventional exit for Brucella. PMID- 22307032 TI - Hepatic cannabinoid receptor-1 mediates diet-induced insulin resistance via inhibition of insulin signaling and clearance in mice. AB - BACKGROUND & AIMS: Obesity-related insulin resistance contributes to cardiovascular disease. Cannabinoid receptor-1 (CB(1)) blockade improves insulin sensitivity in obese animals and people, suggesting endocannabinoid involvement. We explored the role of hepatic CB(1) in insulin resistance and inhibition of insulin signaling pathways. METHODS: Wild-type mice and mice with disruption of CB(1) (CB(1)(-/-) mice) or with hepatocyte-specific deletion or transgenic overexpression of CB(1) were maintained on regular chow or a high-fat diet (HFD) to induce obesity and insulin resistance. Hyperinsulinemic-euglycemic clamp analysis was used to analyze the role of the liver and hepatic CB(1) in HFD induced insulin resistance. The cellular mechanisms of insulin resistance were analyzed in mouse and human isolated hepatocytes using small interfering or short hairpin RNAs and lentiviral knockdown of gene expression. RESULTS: The HFD induced hepatic insulin resistance in wild-type mice, but not in CB(1)(-/-) mice or mice with hepatocyte-specific deletion of CB(1). CB(1)(-/-) mice that overexpressed CB(1) specifically in hepatocytes became hyperinsulinemic as a result of reduced insulin clearance due to down-regulation of the insulin degrading enzyme. However, they had increased hepatic glucose production due to increased glycogenolysis, indicating hepatic insulin resistance; this was further increased by the HFD. In mice with hepatocytes that express CB(1), the HFD or CB(1) activation induced the endoplasmic reticulum stress response via activation of the Bip-PERK-eIF2alpha protein translation pathway. In hepatocytes isolated from human or mouse liver, CB(1) activation caused endoplasmic reticulum stress dependent suppression of insulin-induced phosphorylation of akt-2 via phosphorylation of IRS1 at serine-307 and by inducing the expression of the serine and threonine phosphatase Phlpp1. Expression of CB(1) was up-regulated in samples from patients with nonalcoholic fatty liver disease. CONCLUSIONS: Endocannabinoids contribute to diet-induced insulin resistance in mice via hepatic CB(1)-mediated inhibition of insulin signaling and clearance. PMID- 22307033 TI - Do consumers respond to publicly reported quality information? Evidence from nursing homes. AB - Public reporting of quality information is designed to address information asymmetry in health care markets. Without public reporting, consumers may have little information to help them differentiate quality among providers, giving providers little incentive to compete on quality. Public reporting enables consumers to choose highly ranked providers. Using a four-year (2000-2003) panel dataset, we examine the relationship between report card scores and patient choice of nursing home after the Centers for Medicare and Medicaid Services began publicly reporting nursing home quality information on post-acute care in 2002. We find that the relationship between reported quality and nursing home choice is positive and statistically significant suggesting that patients were more likely to choose facilities with higher reported post-acute care quality after public reporting was initiated. However, the magnitude of the effect was small. We conclude that there has been minimal consumer response to information in the post acute care market. PMID- 22307034 TI - Moral hazard and selection among the poor: evidence from a randomized experiment. AB - Not only does economic theory predict high-risk individuals to be more likely to purchase insurance, but insurance coverage is also thought to crowd out precautionary activities. In spite of stark theoretical predictions, there is conflicting empirical evidence on adverse selection, and evidence on ex ante moral hazard is very scarce. Using data from the Seguro Popular Experiment in Mexico, this paper documents patterns of selection on observables into health insurance as well as the existence of non-negligible ex ante moral hazard. More specifically, the findings indicate that (i) agents in poor self-assessed health prior to the intervention have, all else equal, a higher propensity to take up insurance; and (ii) insurance coverage reduces the demand for self-protection in the form of preventive care. Curiously, however, individuals do not sort based on objective measures of their health. PMID- 22307035 TI - An experimental test of the concentration index. AB - The concentration index is widely used to measure income-related inequality in health. No insight exists, however, whether the concentration index connects with people's preferences about distributions of income and health and whether a reduction in the concentration index reflects an increase in social welfare. We explored this question by testing the central assumption underlying the concentration index and found that it was systematically violated. We also tested the validity of alternative health inequality measures that have been proposed in the literature. Our data showed that decreases in the spread of income and health were considered socially desirable, but decreases in the correlation between income and health not necessarily. Support for a condition implying that the inequality in the distribution of income and in the distribution of health can be considered separately was mixed. PMID- 22307036 TI - An AAV2/5 vector enhances safety of gene transfer to the mouse salivary gland. AB - This study was designed to improve AAV-mediated gene transfer to the murine submandibular salivary glands. Our first aim was to utilize AAV pseudotype vectors, containing the genetic elements of the canonical AAV2, packaged within capsids of AAV serotypes 5, 8, and 9. Having determined that this pseudotyping increased the efficiency of gene transfer to the glands by several orders of magnitude, we next asked whether we could reduce the gene transfer inoculum of the pseudotype while still achieving gene transfer comparable with that achieved with high-dose AAV2. Having achieved gene transfer comparable with that of AAV2 using a pseudotype vector (AAV2/5) at a 100-fold lower dose, our final objective was to evaluate the implications of this lower dose on two pre-clinical parameters of vector safety. To evaluate systemic toxicity, we measured AAV vector sequestration in the liver using qPCR, and found that the 100-fold lower dose reduced the vector recovered from the liver by 300-fold. To evaluate salivary gland function, we undertook whole-proteome profiling of salivary gland lysates two weeks after vector administration and found that high-dose (5 * 109) AAV altered the expression level of ~32% of the entire salivary gland proteome, and that the lower dose (5 * 107) reduced this effect to ~7%. PMID- 22307037 TI - Weekend hospitalization and additional risk of death: an analysis of inpatient data. AB - OBJECTIVE: To assess whether weekend admissions to hospital and/or already being an inpatient on weekend days were associated with any additional mortality risk. DESIGN: Retrospective observational survivorship study. We analysed all admissions to the English National Health Service (NHS) during the financial year 2009/10, following up all patients for 30 days after admission and accounting for risk of death associated with diagnosis, co-morbidities, admission history, age, sex, ethnicity, deprivation, seasonality, day of admission and hospital trust, including day of death as a time dependent covariate. The principal analysis was based on time to in-hospital death. PARTICIPANTS: National Health Service Hospitals in England. MAIN OUTCOME MEASURES: 30 day mortality (in or out of hospital). RESULTS: There were 14,217,640 admissions included in the principal analysis, with 187,337 in-hospital deaths reported within 30 days of admission. Admission on weekend days was associated with a considerable increase in risk of subsequent death compared with admission on weekdays, hazard ratio for Sunday versus Wednesday 1.16 (95% CI 1.14 to 1.18; P < .0001), and for Saturday versus Wednesday 1.11 (95% CI 1.09 to 1.13; P < .0001). Hospital stays on weekend days were associated with a lower risk of death than midweek days, hazard ratio for being in hospital on Sunday versus Wednesday 0.92 (95% CI 0.91 to 0.94; P < .0001), and for Saturday versus Wednesday 0.95 (95% CI 0.93 to 0.96; P < .0001). Similar findings were observed on a smaller US data set. CONCLUSIONS: Admission at the weekend is associated with increased risk of subsequent death within 30 days of admission. The likelihood of death actually occurring is less on a weekend day than on a mid-week day. PMID- 22307038 TI - Unravelling the specific site preference in doping of calcium hydroxyapatite with strontium from ab initio investigations and Rietveld analyses. AB - Strontium can be substituted into the calcium sublattice of hydroxyapatite without a solubility limit. However, recent ab initio simulations carried out at 0 K report endothermic nature of this process. There is also striking discrepancy between experimentally observed preference of Sr doping at Ca-II sites and the first principles calculations, which indicate that a Ca-I site is preferred energetically for the Sr substitution. In this paper we combine insights from Density Functional Theory simulations and regular configurational entropy calculations to determine the site preference of Sr doping in the range of 0-100 at% at finite temperatures. In addition, samples of Sr-HA are synthesized and refinement of the relevant structural information provides benchmark information on the experimental unit cell parameters of Sr-HA. We find that the contribution of the entropy of mixing can efficiently overcome the endothermic excess energy at a temperature typical of the calcining step in the synthesis route of hydroxyapatite (700-950 degrees C). We observe that the most preferential substitution pattern is mixed substitution of Sr regardless of the concentration. For a wet chemical method, carried out at a moderate temperature (90 degrees C), the mixed doping is still slightly favourable at higher Sr-concentrations, except the range at 20% Sr, where Site II substitution is not restricted energetically and equally possible as the mixed doping. We observe a close correspondence between our theoretical results and available experimental data. Hence it should be possible to apply this theory to other divalent dopants in HA, such as Zn(2+), Mg(2+), Pb(2+), Cu(2+), Ba(2+), Cd(2+) etc. PMID- 22307039 TI - Human lymphohematopoietic reconstitution and immune function in immunodeficient mice receiving cotransplantation of human thymic tissue and CD34(+) cells. AB - Small animal models with functional human lymphohematopoietic systems are highly valuable for the study of human immune function under physiological and pathological conditions. Over the last two decades, numerous efforts have been devoted towards the development of such humanized mouse models. This review is focused on human lymphohematopoietic reconstitution and immune function in humanized mice by cotransplantation of human fetal thymic tissue and CD34(+) cells. The potential use of these humanized mice in translational biomedical research is also discussed. PMID- 22307040 TI - Trogocytosis of CD80 and CD86 by induced regulatory T cells. AB - Trogocytosis is a process which involves the transfer of membrane fragments and cell surface proteins between cells. Various types of T cells have been shown to be able to acquire membrane-bound proteins from antigen-presenting cells and their functions can be modulated following trogocytosis. However, it is not known whether induced regulatory T cells (iTregs) can undergo trogocytosis, and if so, what the functional consequences of this process might entail. In this study, we show that iTregs can be generated from CD80(-/-)CD86(-/-) double knockout (DKO) mice. Using flow cytometry and confocal fluorescence microscopy, we demonstrate that iTregs generated from DKO mice are able to acquire both CD80 and CD86 from mature dendritic cells (mDCs) and that the acquisition of CD86 occurs to a higher extent than that of CD80. Furthermore, we found that after co-incubation with iTregs, dendritic cells (DCs) downregulate their surface expression of CD80 and CD86. The trogocytosis of both CD80 and CD86 occurs in a cytotoxic T lymphocyte associated antigen-4 (CTLA-4), CD28 and programmed death ligand-1 (PDL1) independent manner. Importantly, we showed that iTregs that acquired CD86 from mDCs expressed higher activation markers and their ability to suppress naive CD4(+) T-cell proliferation was enhanced, compared to iTregs that did not acquire CD86. These data demonstrate, for the first time, that iTregs can acquire CD80 and CD86 from mDCs, and the acquisition of CD86 may enhance their suppressive function. These findings provide novel understanding of the interaction between iTregs and DCs, suggesting that trogocytosis may play a significant role in iTreg mediated immune suppression. PMID- 22307041 TI - Peli: a family of signal-responsive E3 ubiquitin ligases mediating TLR signaling and T-cell tolerance. AB - E3 ubiquitin ligases play a crucial role in regulating immune receptor signaling and modulating immune homeostasis and activation. One emerging family of such E3s is the Pelle-interacting (Peli) proteins, characterized by the presence of a cryptic forkhead-associated domain involved in substrate binding and an atypical RING domain mediating formation of both lysine (K) 63- and K48-linked polyubiquitin chains. A well-recognized function of Peli family members is participation in the signal transduction mediated by Toll-like receptors (TLRs) and IL-1 receptor. Recent gene targeting studies have provided important insights into the in vivo functions of Peli1 in the regulation of TLR signaling and inflammation. These studies have also extended the biological functions of Peli1 to the regulation of T-cell tolerance. Consistent with its immunoregulatory functions, Peli1 responds to different immune stimuli for its gene expression and catalytic activation. In this review, we discuss the recent progress, as well as the historical perspectives in the regulation and biological functions of Peli. PMID- 22307042 TI - Synergistic and feedback signaling mechanisms in the regulation of inflammation in respiratory infections. AB - Pneumonia, the most typical and frequent lower respiratory tract infection (LRTI), is a leading cause of health problems in the United States. Bacteria represent the most prevailing cause of pneumonia in both children and adults. Although pneumonia with a single bacterial infection is common, a significant portion of patients with pneumonia is polymicrobial. This infection is often complexed with other physiological factors such as cytokines and growth factors. Nontypeable Haemophilus influenzae (NTHi) is the most frequently recovered Gram negative bacterial pathogen in the respiratory system and induces strong inflammatory responses. NTHi also synergizes with other respiratory pathogens, such as Streptococcus pneumoniae and respiratory viruses and pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha). It is noteworthy that NTHi not only synergizes with growth factors such as transforming growth factor beta (TGF-beta), but also utilizes growth factor receptors such as TGF-beta receptor and epidermal growth factor receptor (EGFR), to enhance inflammatory responses. Although appropriate inflammation is a protective response against invading pathogens, an uncontrolled inflammatory response is often detrimental to the host. Thus, inflammation must be tightly regulated. The human immune system has evolved strategies for controlling overactive inflammatory response. One such important mechanism is via regulation of negative feedback regulators for inflammation. CYLD, a multifunctional deubiquitinase, was originally reported as a tumor suppressor, but was recently identified as a negative regulator for nuclear factor-kappa B (NF-kappaB) signaling. It is induced by NTHi and TNF-alpha via a NF-kappaB-dependent mechanism, thereby serving as an inducible negative feedback regulator for tightly controlling inflammation in NTHi infection. PMID- 22307043 TI - Arabidopsis growth and defense are modulated by bacterial quorum sensing molecules. AB - N-acyl-homoserine lactones (AHLs) play an important role in the communication within the rhizosphere; they serve as a chemical base for interactions within and between different species of Gram-negative bacteria. Not only bacteria, also plants perceive and react to AHLs with diverse responses. Here we describe a negative correlation between the length of AHLs' lipid chains and the observed growth promotion in Arabidopsis thaliana. Moreover, we speculate on a positive correlation between the reinforcement of defense mechanisms and the length of the lipid moieties. Observation presented here may be of great importance for understanding of the complex interplay between plants and their environment, as well as for agronomic applications. PMID- 22307044 TI - ELF3 recruitment to the PRR9 promoter requires other Evening Complex members in the Arabidopsis circadian clock. AB - Biological timekeeping is essential for proper growth and development. Organisms such as the model plant Arabidopsis use the circadian clock to coordinate biological processes with the environment so that changes in conditions are anticipated and processes favorably phased. Despite the identification of numerous clock genes, knowledge of their molecular connectivity and influence on output programs remains limited. We recently showed LUX encodes a sequence specific DNA-binding protein that directly regulates expression of the morning clock gene PRR9. We also showed that LUX interacts with the evening-phased proteins ELF3 and ELF4 to form a complex called the Evening Complex (EC). The EC binds the PIF4 and PIF5 promoters to control hypocotyl growth as a clock output. Here we provide evidence that LUX also recruits ELF3 to the PRR9 promoter. As with the PIF4 and PIF5 promoters, both LUX and its close homolog NOX are required for recruitment. Hence the entire EC likely functions together as part of the core clock oscillator to optimize plant fitness. PMID- 22307045 TI - Metabolism and roles of phosphatidylinositol 3-phosphate in pollen development and pollen tube growth in Arabidopsis. AB - Phosphoinositides play important roles in eukaryotic cells, although they constitute a minor fraction of total cellular lipids. Specific kinases and phosphatases function on the regulation of phosphoinositide levels. Phosphatidylinositol 3-phosphate (PtdIns3P), a molecule of phosphoinositides regulates multiple aspects of plant growth and development. In this mini-review, we introduce and discuss the kinases and phosphatases involved in PtdIns3P metabolism and their roles in pollen development and pollen tube growth in Arabidopsis. PMID- 22307046 TI - A role for mechanosensitive channels in chloroplast and bacterial fission. AB - The division site in both chloroplasts and bacteria is established by the medial placement of the FtsZ ring, a process that is in part regulated by the evolutionarily conserved components of the Min system. We recently showed that mechanosensitive ion channels influence FtsZ ring assembly in both Arabidopsis thaliana chloroplasts and in Escherichia coli; in chloroplasts they do so through the same genetic pathway as the Min system. Here we describe the effect of heterologous expression of the Arabidopsis MS channel homolog MSL2 on FtsZ ring placement in E. coli. We also discuss possible molecular mechanisms by which MS channels might influence chloroplast or bacterial division. PMID- 22307047 TI - Neofunctionalization within the Omp85 protein superfamily during chloroplast evolution. AB - The Toc75 and OEP80 proteins reside in the chloroplast outer envelope membrane. Both are members of the Omp85 superfamily of beta-barrel proteins, and both are essential in Arabidopsis plants with important roles throughout development. Toc75 forms the translocation channel of the TOC complex, which is responsible for importing nucleus-encoded proteins into chloroplasts, while the function of OEP80 remains uncertain. Deficiency of Toc75 in plants that have artificially reduced OEP80 levels suggests that the latter may be involved in the biogenesis of beta-barrel proteins, in similar fashion to Omp85-related proteins in other systems. To elucidate the evolutionary relationship between the two proteins, we conducted a phylogenetic analysis using 48 sequences from diverse species. This indicated that Toc75 and OEP80 belong to sister groups in the Omp85 superfamily, and originate from a gene duplication in an ancient eukaryotic organism > 1.2 billion years ago. Our analysis also supports the notion that the Toc75 family has undergone a phase of neofunctionalization to accommodate the organelle's newly acquired need to import proteins. PMID- 22307048 TI - Common neuropathic itch syndromes. AB - Patients with chronic itch are diagnosed and treated by dermatologists. However, itch is a neural sensation and some forms of chronic itch are the presenting symptoms of neurological diseases. Dermatologists need some familiarity with the most common neuropathic itch syndromes to initiate diagnostic testing and to know when to refer to a neurologist. This review summarizes current knowledge, admittedly incomplete, on neuropathic itch caused by diseases of the brain, spinal cord, cranial or spinal nerve-roots, and peripheral nerves. PMID- 22307049 TI - Benzoquinolateplatinum(II) complexes as building blocks in the synthesis of Pt-Ag extended structures. AB - The reaction between (NBu(4))[Pt(bzq)(C(6)F(5))(2)] (1, bzq = 7,8-benzoquinolate) and AgClO(4) in a 1 : 1 molar ratio, in acetone, gives the polymer [{Pt(bzq)(C(6)F(5))(2)}Ag](n) (2). The reaction of 2 with equimolecular amounts of PPh(3) and SC(4)H(8) (tht) produces the bimetallic complexes [{Pt(bzq)(C(6)F(5))(2)}AgL] (L = PPh(3) (3), tht (4)). For L = py, decomposition takes place and [Pt(bzq)(C(6)F(5))py] (5) is obtained. All these complexes have been characterized by X-ray diffraction. The most interesting features of complexes 2-4 is the presence of Pt-Ag bonds, with Pt-Ag distances of ca. 2.75 A. Besides, the silver centres establish short eta(1) bonding interactions with the C(ipso) of the bzq ligands, with distances Ag-C of ca. 2.45 A. Complex 2 is a one dimensional infinite chain in which the fragments "Pt(bzq)(C(6)F(5))(2)(-)" and Ag(+) alternate. On the other hand, complexes 1 and 3-5 show intermolecular pairing through pi...pi interactions between the aromatic rings of the bzq ligand, having interplanar separations of ca. 3.5 A. Complex 2 dissolves in donor solvents (acetone, THF) as discrete bimetallic solvated fragments [{Pt(bzq)(C(6)F(5))(2)}AgS(n)] (S = solvent), similar to complexes 3 and 4. The persistence of the Pt-Ag bond in 2-4, supported by multinuclear NMR spectroscopy, causes a significant blue-shift in the lowest-lying absorption in relation to 1. This fact is attributed (TD-DFT) to a remarkable modification of the orbitals contributing to the HOMO, which changes the character of the transition from (1)LC/(1)MLCT in 1 to admixture (1)L'LCT/(1)MLCT in the bimetallic complexes. The low energy feature (490-530 nm) of 2 in solid state is attributed to CT from the Pt fragments to the Ag centers. Complexes 2-4 are only emissive in rigid media (solid and glasses). In the solid state, the metallic chain 2 exhibits a bright orange emission (560 nm, 298 K; 590 nm, 77 K), assigned to an excited state involving charge transfer from the platinum fragment with a remarkable contribution of C(6)F(5) (Ar(f)) rings to the Pt-Ag bond ((3)LMM'CT/(3)L'M'CT). However, 3 and 4 exhibit in solid state at 298 K a vibronic band, which is clearly resolved in two close non-equilibrated bands at 77 K in 3, tentatively ascribed to a mixture of (3)MLCT/(3)L'LCT transitions modified by the formation of the Pt-Ag bond. In glassy solution (77 K) 2-4 display a vibronic emission ascribed primarily to (3)LC character. PMID- 22307050 TI - Quick and simple estimation of bacteria using a fluorescent paracetamol dimer-Au nanoparticle composite. AB - Rapid, simple and sensitive detection of bacterial contamination is critical for safeguarding public health and the environment. Herein, we report an easy method of detection as well as enumeration of the bacterial cell number on the basis of fluorescence quenching of a non-antibacterial fluorescent nanocomposite, consisting of paracetamol dimer (PD) and Au nanoparticles (NPs), in the presence of bacteria. The composite was synthesized by reaction of paracetamol (p hydroxyacetanilide) with HAuCl(4). The Au NPs of the composite were characterized using UV-Vis spectroscopy, transmission electron microscopy (TEM), X-ray diffraction and selected area electron diffraction analysis. The paracetamol dimer in the composite showed emission peak at 435 nm when excited at 320 nm. The method successfully detected six bacterial strains with a sensitivity of 100 CFU mL(-1). The gram-positive and gram-negative bacteria quenched the fluorescence of the composite differently, making it possible to distinguish between the two. The TEM analysis showed interaction of the composite with bacteria without any apparent damage to the bacteria. The chi-square test established the accuracy of the method. Quick, non-specific and highly sensitive detection of bacteria over a broad range of logarithmic dilutions within a short span of time demonstrates the potential of this method as an alternative to conventional methods. PMID- 22307051 TI - Photochemical investigation of the IR absorption bands of molecular oxygen in organic and aqueous environment. AB - It is shown that the weak IR absorption bands corresponding to the forbidden triplet-singlet transitions in oxygen molecules can be reliably studied in air saturated solvents under ambient conditions using measurements of the photooxygenation rates of singlet oxygen traps (1,3-diphenylisobenzofuran or uric acid) upon direct excitation of oxygen molecules by IR diode lasers. The best results were obtained from comparison of the oxygenation rates upon direct and photosensitized singlet oxygen excitation. In the present paper, this method was applied to estimation of the absorbance (A(ox)) and molar absorption coefficients (epsilon(ox)) corresponding to the oxygen absorption bands at 765 and 1273 nm in carbon tetrachloride, acetone, alcohols and water. In carbon tetrachloride, the band at 1073 nm was also investigated. Correlation of the obtained data with the luminescence spectra and radiative rate constants of singlet oxygen, contribution of oxygen dimols and biological significance of the studied effects are discussed. PMID- 22307052 TI - The workshop on signatures of medical and industrial isotope production - WOSMIP; Strassoldo, Italy, 1-3 July 2009. AB - Radiopharmaceuticals make contributions of inestimable value to medical practice. With growing demand new technologies are being developed and applied worldwide. Most diagnostic procedures rely on (99m)Tc and the use of uranium targets in reactors is currently the favored method of production, with 95% of the necessary (99)Mo parent currently being produced by four major global suppliers. Coincidentally there are growing concerns for nuclear security and proliferation. New disarmament treaties such as the Comprehensive Nuclear-Test-Ban Treaty (CTBT) are coming into effect and treaty compliance-verification monitoring is gaining momentum. Radioxenon emissions (isotopes Xe-131, 133, 133m and 135) from radiopharmaceutical production facilities are of concern in this context because radioxenon is a highly sensitive tracer for detecting nuclear explosions. There exists, therefore, a potential for confusing source attribution, with emissions from radiopharmaceutical-production facilities regularly being detected in treaty compliance-verification networks. The CTBT radioxenon network currently under installation is highly sensitive with detection limits approaching 0.1 mBq/m3 and, depending on transport conditions and background, able to detect industrial release signatures from sites thousands of kilometers away. The method currently employed to distinguish between industrial and military radioxenon sources involves plots of isotope ratios (133m)Xe/(131m)Xe versus (135)Xe/(133)Xe, but source attribution can be ambiguous. Through the WOSMIP Workshop the environmental monitoring community is gaining a better understanding of the complexities of the processes at production facilities, and the production community is recognizing the impact their operations have on monitoring systems and their goal of nuclear non-proliferation. Further collaboration and discussion are needed, together with advances in Xe trapping technology and monitoring systems. Such initiatives will help in addressing the dichotomy which exists between expanding production and improving monitoring sensitivity, with the ultimate aim of enabling unambiguous distinction between different nuclide signatures. PMID- 22307053 TI - Structure and mechanism of the UvrA-UvrB DNA damage sensor. AB - Nucleotide excision repair (NER) is used by all organisms to eliminate DNA lesions. We determined the structure of the Geobacillus stearothermophilus UvrA UvrB complex, the damage-sensor in bacterial NER and a new structure of UvrA. We observe that the DNA binding surface of UvrA, previously found in an open shape that binds damaged DNA, also exists in a closed groove shape compatible with native DNA only. The sensor contains two UvrB molecules that flank the UvrA dimer along the predicted path for DNA, ~80 A from the lesion. We show that the conserved signature domain II of UvrA mediates a nexus of contacts among UvrA, UvrB and DNA. Further, in our new structure of UvrA, this domain adopts an altered conformation while an adjacent nucleotide binding site is vacant. Our findings raise unanticipated questions about NER and also suggest a revised picture of its early stages. PMID- 22307054 TI - Concentration-dependent control of pyruvate kinase M mutually exclusive splicing by hnRNP proteins. AB - Expression of the mammalian pyruvate kinase M (PKM) gene provides an important example of mutually exclusive splicing. We showed previously that the hnRNP proteins A1, A2 and PTB have a crucial role in this process. Here we provide evidence that concentration-dependent interactions involving a network of these proteins are sufficient to determine the outcome of PKM splicing. At high concentrations, such as those found in most cancer cells, hnRNPA1 binding to two sites in the upstream regulated exon (exon 9) orchestrates cooperative interactions leading to exon 9 exclusion. At lower concentrations, binding shifts to downstream intronic sites, such that exon 9 is included and exon 10 mainly excluded, with any mRNA including both exons degraded by nonsense-mediated decay. Together, our results provide a mechanism by which a few general factors control alternative splicing of a widely expressed transcript. PMID- 22307055 TI - Structural characterization of full-length NSF and 20S particles. AB - The 20S particle, which is composed of the N-ethylmaleimide-sensitive factor (NSF), soluble NSF attachment proteins (SNAPs) and the SNAP receptor (SNARE) complex, has an essential role in intracellular vesicle fusion events. Using single-particle cryo-EM and negative stain EM, we reconstructed four related three-dimensional structures: Chinese hamster NSF hexamer in the ATPgammaS, ADP AlFx and ADP states, and the 20S particle. These structures reveal a parallel arrangement between the D1 and D2 domains of the hexameric NSF and characterize the nucleotide-dependent conformational changes in NSF. The structure of the 20S particle shows that it holds the SNARE complex at two interaction interfaces around the C terminus and N-terminal half of the SNARE complex, respectively. These findings provide insight into the molecular mechanism underlying disassembly of the SNARE complex by NSF. PMID- 22307056 TI - ERK1 and ERK2 regulate embryonic stem cell self-renewal through phosphorylation of Klf4. AB - Understanding and controlling the mechanism by which stem cells balance self renewal versus differentiation is of great importance for stem cell therapeutics. Klf4 promotes the self-renewal of embryonic stem cells, but the precise mechanism regulating this role of Klf4 is unclear. We found that ERK1 or ERK2 binds the activation domain of Klf4 and directly phosphorylates Klf4 at Ser123. This phosphorylation suppresses Klf4 activity, inducing embryonic stem cell differentiation. Conversely, inhibition of Klf4 phosphorylation enhances Klf4 activity and suppresses embryonic stem cell differentiation. Notably, phosphorylation of Klf4 by ERKs causes recruitment and binding of the F-box proteins betaTrCP1 or betaTrCP2 (components of an ubiquitin E3 ligase) to the Klf4 N-terminal domain, which results in Klf4 ubiquitination and degradation. Overall, our data provide a molecular basis for the role of ERK1 and ERK2 in regulating Klf4-mediated mouse embryonic stem cell self-renewal. PMID- 22307058 TI - Oligodendrocyte-protection and remyelination post-spinal cord injuries: a review. AB - In the past four decades, the main focus of investigators in the field of spinal cord regeneration has been to devise therapeutic measures that enhance neural regeneration. More recently, emphasis has been placed on enhancing remyelination and providing oligodendrocyte-protection after a spinal cord injury (SCI). Demyelination post-SCI is part of the cascading secondary injury that takes place immediately after the primary insult; therefore, therapeutic measures are needed to reduce oligodendrocyte death and/or enhance remyelination during the acute stage, preserving neurological functions that would be lost otherwise. In this review a thorough investigation of the oligodendrocyte-protective and remyelinative molecular therapies available to date is provided. The advent of new biomaterials shown to promote remyelination post-SCI is discussed mainly in the context of a combinatorial approach where the biomaterial also provides drug delivery capabilities. The aim of these molecular and biomaterial-based therapies is twofold: (1) oligodendrocyte-protective therapy, which involves protecting already existing oligodendrocytes from undergoing apoptosis/necrosis; and (2) inductive remyelination, which involves harnessing the remyelinative capabilities of endogenous oligodendrocyte precursor cells (OPCs) at the lesion site by providing a suitable environment for their migration, survival, proliferation and differentiation. From the evidence reported in the literature, we conclude that the use of a combinatorial approach including biomaterials and molecular therapies would provide advantages such as: (1) sustained release of the therapeutic molecule, (2) local delivery at the lesion site, and (3) an environment at the site of injury that promotes OPC migration, differentiation and remyelination. PMID- 22307057 TI - Dissecting the age-related decline on spatial learning and memory tasks in rodent models: N-methyl-D-aspartate receptors and voltage-dependent Ca2+ channels in senescent synaptic plasticity. AB - In humans, heterogeneity in the decline of hippocampal-dependent episodic memory is observed during aging. Rodents have been employed as models of age-related cognitive decline and the spatial water maze has been used to show variability in the emergence and extent of impaired hippocampal-dependent memory. Impairment in the consolidation of intermediate-term memory for rapidly acquired and flexible spatial information emerges early, in middle-age. As aging proceeds, deficits may broaden to include impaired incremental learning of a spatial reference memory. The extent and time course of impairment has been be linked to senescence of calcium (Ca2+) regulation and Ca2+-dependent synaptic plasticity mechanisms in region CA1. Specifically, aging is associated with altered function of N-methyl-D aspartate receptors (NMDARs), voltage-dependent Ca2+ channels (VDCCs), and ryanodine receptors (RyRs) linked to intracellular Ca2+ stores (ICS). In young animals, NMDAR activation induces long-term potentiation of synaptic transmission (NMDAR-LTP), which is thought to mediate the rapid consolidation of intermediate term memory. Oxidative stress, starting in middle-age, reduces NMDAR function. In addition, VDCCs and ICS can actively inhibit NMDAR-dependent LTP and oxidative stress enhances the role of VDCC and RyR-ICS in regulating synaptic plasticity. Blockade of L-type VDCCs promotes NMDAR-LTP and memory in older animals. Interestingly, pharmacological or genetic manipulations to reduce hippocampal NMDAR function readily impair memory consolidation or rapid learning, generally leaving incremental learning intact. Finally, evidence is mounting to indicate a role for VDCC-dependent synaptic plasticity in associative learning and the consolidation of remote memories. Thus, VDCC-dependent synaptic plasticity and extrahippocampal systems may contribute to incremental learning deficits observed with advanced aging. PMID- 22307059 TI - Insights into cortical mechanisms of behavior from microstimulation experiments. AB - Even the simplest behaviors depend on a large number of neurons that are distributed across many brain regions. Because electrical microstimulation can change the activity of localized subsets of neurons, it has provided valuable evidence that specific neurons contribute to particular behaviors. Here we review what has been learned about cortical function from behavioral studies using microstimulation in animals and humans. Experiments that examine how microstimulation affects the perception of stimuli have shown that the effects of microstimulation are usually highly specific and can be related to the stimuli preferred by neurons at the stimulated site. Experiments that ask subjects to detect cortical microstimulation in the absence of other stimuli have provided further insights. Although subjects typically can detect microstimulation of primary sensory or motor cortex, they are generally unable to detect stimulation of most of cortex without extensive practice. With practice, however, stimulation of any part of cortex can become detected. These training effects suggest that some patterns of cortical activity cannot be readily accessed to guide behavior, but that the adult brain retains enough plasticity to learn to process novel patterns of neuronal activity arising anywhere in cortex. PMID- 22307061 TI - Chemoradiation and adjuvant chemotherapy in advanced cervical adenocarcinoma. AB - PURPOSE: The optimal treatment of women with advanced adenocarcinoma of uterine cervix is still undefined. We compared concurrent chemoradiation (CCRT) and adjuvant cisplatin-based chemotherapy with CCRT alone for advanced cervical adenocarcinoma in a randomized trial at the Hunan Provincial Tumor Hospital in China. METHODS: From 1998 to 2007, 880 patients with clinical FIGO stages IIB-IVA cervical adenocarcinoma were randomized to receive either CCRT or chemoradiation with one cycle of neo-adjuvant chemotherapy with Paclitaxel (135 mg/m(2))+Cisplatin (75 mg/m(2)) before receiving radiation and two cycles of consolidation chemotherapy with the same drugs after radiotherapy in 3-week intervals. The disease control and survival rates were calculated using the Kaplan-Meier method. RESULTS: All patients completed the treatment plan. 340 patients have relapsed, with a median follow-up duration of 60 months. Patients who received chemoradiation with adjuvant chemotherapy showed a significantly longer disease-free (P<.05), cumulative survival (P<.05) and long-term local tumor control (P<.05). Patients who received CCRT alone had significantly more distant metastasis and pelvic failure than those who received chemoradiation with adjuvant chemotherapy (P<.05). CONCLUSION: Incorporating neo-adjuvant and consolidation chemotherapy with Paclitaxel and Cisplatin into concomitant chemoradiation is highly effective, safe and may be a very promising treatment protocol for advanced cervical adenocarcinoma. PMID- 22307062 TI - Quality of life and survival in advanced cervical cancer: a Gynecologic Oncology Group study. AB - PURPOSE: To determine associations between pretreatment health-related quality of life subscales with progression-free (PFS) and overall survival (OS) in advanced and recurrent cervical cancer. PATIENTS AND METHODS: Patients included those participating in Gynecologic Oncology Group advanced or recurrent cervical cancer phase III treatment trials who completed the Functional Assessment of Cancer Therapy for patients with cervical cancer (FACT-Cx) and a single-item pain scale at study entry. The FACT-Cx includes five domains: physical (PWB), emotional (EWB), social (SWB), functional well being (FWB), and cervix cancer subscale (CCS). A high quality of life (QoL) score reflects better QoL. After stratifying by protocol and adjusting for patient and disease characteristics, a Cox proportional hazards model was fitted for each subscale as a continuous variable. If statistically significant, (p<0.05), an analysis on mean item scores (MIS) was performed. RESULTS: Nine-hundred-ninety-one patients were enrolled from 1997 to 2007. The majority (87%) had recurrent disease. After adjustment for covariates and predictors, only the PWB domain (better physical QoL) was associated with improved OS [HR 0.96 95% CI 0.95-0.98; p<0.001]. When classifying patients based on the MIS of each subscale, the patients with the lowest risk of death were likely to report less compromised QoL (MIS>3) for PWB [HR 0.44 (0.33-0.58) P<0.001], FWB [0.49 (0.38-0.62) P<0.001], and CCS [0.48 (0.38-0.61) P<0.001]. CONCLUSION: The pretreatment patient-reported PWB as measured by the PWB subscale of the FACT-Cx, is significantly associated with survival in advanced cervical cancer trials, even after controlling for known prognostic factors. PMID- 22307060 TI - GPCR mediated regulation of synaptic transmission. AB - Synaptic transmission is a finely regulated mechanism of neuronal communication. The release of neurotransmitter at the synapse is not only the reflection of membrane depolarization events, but rather, is the summation of interactions between ion channels, G protein coupled receptors, second messengers, and the exocytotic machinery itself which exposes the components within a synaptic vesicle to the synaptic cleft. The focus of this review is to explore the role of G protein signaling as it relates to neurotransmission, as well as to discuss the recently determined inhibitory mechanism of Gbetagamma dimers acting directly on the exocytotic machinery proteins to inhibit neurotransmitter release. PMID- 22307063 TI - Introduction of a computer-based surgical platform in the surgical care of patients with newly diagnosed uterine cancer: outcomes and impact on approach. AB - OBJECTIVE: To assess the introduction of computer-based surgery (ie, robotic surgery [RBT]) in the treatment of patients with newly diagnosed uterine cancer. METHODS: We identified all patients who presented to our institution for initial surgical care of newly diagnosed uterine cancer from 5/1/07-12/31/10. Perioperative outcomes of laparotomy cases were compared to those of laparoscopic (LSC) or RBT cases. Complications within 30 days of surgery were graded. RESULTS: Of 752 patients, the planned approach was laparotomy in 103 (14%), LSC in 302 (40%), and RBT in 347 (46%). The rate of laparotomy for any reason (planned or converted) was 39% in 2007 compared to 18% in 2010 (P<0.001). Preoperative characteristics for LSC and RBT cases were similar, except 10% versus 15%, respectively, were morbidly obese (P=0.049). The extent of procedure, total nodal counts, and overall complications were similar between the LSC and RBT cases. The median length of stay was shorter for RBT cases (P<0.001). The median total room and operative times were longer for RBT cases (P<0.001), mainly due to cases in which the surgeon had less than ~40 RBT cases of experience. CONCLUSIONS: Robotics can be efficiently introduced into the surgical care of patients with newly diagnosed uterine cancers. RBT cases require the same operative times as LSC cases after accounting for the 40-case learning curve. Both approaches result in similar excellent patient outcomes and remain reasonable approaches for this disease. The introduction of robotics may lead to further reduction in the rate of laparotomy. PMID- 22307064 TI - Improved survival related to changes in endometrial cancer treatment, a 30-year population based perspective. AB - OBJECTIVE: Age adjusted incidence rate for uterine cancers in Norway has increased over last three decades from 12.2/100.000 (1981-90) to 16.0 (2001 2010). Corresponding 5-year survival increased nationally from 76.3% to 83.3%. METHODS: We wanted to investigate how changes in therapeutic strategies during a 30-year period are reflected in survival changes through careful characterization of a population-based series of 1077 endometrial carcinoma patients from Hordaland County, Norway. RESULTS: In concordance with increase in endometrial cancer nationally, the number of patients treated from Hordaland County rose from 286 (1981-1990) through 307 (1991-2000) to 484 (2001-2010). Main treatment changes included increase in routine pelvic lymphadenectomy from 0% through 9% to 77%, adjuvant chemotherapy from 0% through 3% to 9% and a dramatic reduction in adjuvant radiotherapy from 75% through 48% to 12% (all P<0.001). Body mass index increased significantly during this 30-year period, as did the 5-year disease specific survival: from 75.8 through 80.2 to 86.9% (P=0.002) and overall survival from 67.8 through 71.7 to 77.8% (P=0.03). CONCLUSION: Improved overall and disease specific survival for endometrial carcinoma patients over the last 30 years is demonstrated in a population-based setting. Increasing BMI among patients and a change in treatment strategy with reduction in adjuvant radiotherapy and more extensive surgery is demonstrated for the same period. PMID- 22307065 TI - Aldehyde dehydrogenase activity is a cancer stem cell marker of tongue squamous cell carcinoma. AB - Accumulating data reveal that aldehyde dehydrogenase (ALDH) activity is a cancer stem cell marker in several types of human cancers. Whether ALDH also defines cancer stem cells of tongue squamous cell carcinoma is unknown. In the present study, we performed the Aldefluor assay to detect ALDH enzymatic activity, and used flow cytometry to isolate ALDH+ and ALDH- cells based on their ALDH activity in the Tca8113 tongue squamous cell carcinoma cell line. We found that Tca8113 cells harbored 1.3% of ALDH+ cells, which exhibited higher proliferation capacity than their ALDH- counterparts and parental cells. Sorted ALDH+ cells were able to differentiate and generate ALDH- cells in vitro. Moreover, in serum-free medium, ALDH+, but not ALDH- cells, survived and formed tumorspheres. The suppression subtractive hybridization assay revealed 68 overexpressed or underexpressed genes in the ALDH+ subpopulation relative to ALDH- cells, which included a set of known cancer stem cell-related genes. Thus, our data demonstrated that a small subset of Tca8113 cells with high ALDH enzymatic activity display characteristics of cancer stem cells, suggesting that ALDH activity may be a cancer stem cell marker for tongue squamous cell carcinoma. PMID- 22307066 TI - A femtosecond fluorescence study of vibrational relaxation and cooling dynamics of UV dyes. AB - We present a femtosecond broad-band fluorescence up-conversion study of the vibrational relaxation dynamics of two UV chromophores, 2,5-diphenyloxazole (PPO) and para-terphenyl (pTP), pumped with a large excess of vibrational energy (>2000 cm(-1)). The band narrowing of the transient fluorescence spectrum reflects a biphasic cooling process in a few hundreds of fs and a few ps. In the sub-ps regime, our data suggest a structural rearrangement in the excited state, followed by thermalization of the excess energy. These dynamics affect the fluorescence spectra of PPO and pTP in different ways. In PPO, the damping of a low frequency vibrational wavepacket and a significant sub-ps narrowing of the band characterize the vibrational relaxation. In pTP, the latter is faster and appears as a red shift with distortion of the band in <200 fs. PMID- 22307067 TI - Synthesis, characterization and photocatalytic property of AgBr/BiPO4 heterojunction photocatalyst. AB - A novel heterojunction AgBr/BiPO(4) photocatalyst was synthesized with the hydrothermal method. The photocatalyst was characterized by X-Ray powder Diffraction (XRD), Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Spectrometry (EDS), Transmission Electron Microscopy (TEM), X-ray Photoelectron Spectrscopy (XPS) and Diffuse Reflectance Spectroscopy (DRS). The XRD, SEM-EDS, TEM and XPS analyses indicated that the heterojunction structure formed during the process of hydrothermal treatment. The photocatalytic activity of the photocatalysts was evaluated by degradation of methylene blue dye (MB). The results indicated that the AgBr/BiPO(4) heterojunction exhibited a much higher photocatalytic activity than the pure BiPO(4). The mechanism of the enhancing AgBr/BiPO(4) heterojunction's photocatalytic activity was discussed. It was also found that the photocatalytic degradation of MB over AgBr/BiPO(4) heterojunction photocatalysts followed the pseudo-first-order reaction model. PMID- 22307068 TI - Predicting maintenance or achievement of healthy weight in children: the impact of changes in physical fitness. AB - Physical fitness is often inversely associated with adiposity in children cross sectionally, but the effect of becoming fit or maintaining fitness over time on changes in weight status has not been well studied in children. We investigated the impact of changes in fitness over 1-4 years of follow-up on the maintenance or achievement of healthy weight among 2,793 schoolchildren who were first measured as 1st to 7th graders. Students were classified as "fit" or "underfit" according to age- and gender-specific norms in five fitness domains: endurance, agility, flexibility, upper body strength, and abdominal strength. Weight status was dichotomized by BMI percentile: "healthy weight" (<85th percentile) or "overweight/obese" (>=85th percentile). At baseline, of the 38.3% overweight/obese children, 81.9% (N = 875) were underfit. Underfit overweight students were more likely to achieve healthy weight if they achieved fitness (boys: odds ratio (OR) = 2.68, 95% confidence interval (CI) = 1.24-5.77; girls: OR = 4.67, 95%CI = 2.09-10.45). Initially fit overweight children (N = 194) were more likely to achieve healthy weight if they maintained fitness (boys: OR = 11.99, 95%CI = 2.18-65.89; girls: OR = 2.46, 95%CI = 1.04-5.83). Similarly, initially fit healthy-weight children (N = 717) were more likely to maintain healthy weight if they maintained fitness (boys: OR 3.70, 95%CI = 1.40-9.78; girls: OR = 4.14, 95%CI = 1.95-8.78). Overweight schoolchildren who achieve or maintain physical fitness are more likely to achieve healthy weight, and healthy weight children who maintain fitness are more likely to maintain healthy weight. School-based policies/practices that support physical fitness may contribute to obesity reduction and maintenance of healthy weight among schoolchildren. PMID- 22307070 TI - Free-choice and no-choice high-fat diets affect striatal dopamine D2/3 receptor availability, caloric intake, and adiposity. AB - Different types of high-fat (HF) diets are used to study diet-induced obesity (DIO) in rodents and this has led to different phenotypes. This study assesses whether different HF diets differentially affect striatal dopamine D(2/3) receptor (DRD(2/3)) availability, as decreased striatal DRD(2/3) availability has been implicated in obesity in relation to reward deficiency for food. Thirty rats were randomized to either a free-choice HF diet (HF-choice), a premixed HF diet (HF-no-choice), or a standard chow diet for 28 days. Striatal DRD(2/3) was measured using (123)I-IBZM storage phosphor imaging at day 29. DRD(2/3) availability was significantly decreased in the dorsal striatum in the HF-choice rats compared to chow rats, but not in HF-no-choice rats. Additionally, caloric intake of the HF-choice rats was significantly higher than that of HF-no-choice rats and serum leptin and percentage abdominal fat store weight of total body weight were significantly higher in the HF-choice rats compared to chow rats. These preliminary results suggest that the choice element in HF diets, which is possibly related to the motivational aspects of eating, leads to overconsumption and to a distinct state of obesity. These results are relevant for future studies on DIO when considering choice of diet type. PMID- 22307072 TI - Cocaine-induced midline destructive lesion and Wegener granulomatosis. PMID- 22307071 TI - Rapid identification of monospecific monoclonal antibodies using a human proteome microarray. AB - To broaden the range of tools available for proteomic research, we generated a library of 16,368 unique full-length human ORFs that are expressible as N terminal GST-His(6) fusion proteins. Following expression in yeast, these proteins were then individually purified and used to construct a human proteome microarray. To demonstrate the usefulness of this reagent, we developed a streamlined strategy for the production of monospecific monoclonal antibodies that used immunization with live human cells and microarray-based analysis of antibody specificity as its central components. We showed that microarray-based analysis of antibody specificity can be performed efficiently using a two dimensional pooling strategy. We also demonstrated that our immunization and selection strategies result in a large fraction of monospecific monoclonal antibodies that are both immunoblot and immunoprecipitation grade. Our data indicate that the pipeline provides a robust platform for the generation of monoclonal antibodies of exceptional specificity. PMID- 22307073 TI - Contralateral clipping of middle cerebral artery aneurysms: rationale, indications, and surgical technique. AB - BACKGROUND: Contralateral clipping of middle cerebral artery (MCA) aneurysms seems dangerous and ill advised but could become an important technique because of the prevalence of MCA aneurysms, the limitations of endovascular therapy, and increasing interest in less invasive techniques. OBJECTIVE: To define patient selection, surgical technique, and results with contralateral MCA aneurysm clipping. METHODS: Forty-two patients with bilateral MCA aneurysms were treated either in 1 stage with a single craniotomy and contralateral aneurysm clipping (group 1, 11 patients) or in 2 stages with bilateral craniotomy (group 2, 31 patients). Surgical technique consisted of ipsilateral sylvian fissure split, subfrontal dissection, contralateral sylvian fissure split, mobilization of medial orbital gyrus, and contralateral aneurysm clipping. RESULTS: Group 1 patients were older than group 2 patients (60.3 vs 55.4 years, respectively). Clinical presentation with subarachnoid hemorrhage was less common in group 1. Nine group 1 patients (82%) had left-sided craniotomies, and the ipsilateral aneurysm was larger than the contralateral aneurysm. All aneurysms were clipped without intraoperative complications (136 aneurysms). Mean neurosurgical charges were decreased by contralateral MCA aneurysm clipping: $39 297 in group 1 vs $57 977 in group 2. CONCLUSION: Contralateral MCA aneurysm clipping can be viewed as an extreme microsurgical technique or as a less invasive technique that spares patients a second craniotomy in the management of bilateral aneurysms. This technique is acceptable in selected patients with contralateral aneurysms that are unruptured, have simple necks, project inferiorly or anteriorly, are associated with short M1 segments, and reside in older patients with sylvian fissures widened by brain atrophy. PMID- 22307074 TI - Coagulopathy after traumatic brain injury. AB - Traumatic brain injury has long been associated with abnormal coagulation parameters, but the exact mechanisms underlying this phenomenon are poorly understood. Coagulopathy after traumatic brain injury includes hypercoagulable and hypocoagulable states that can lead to secondary injury by either the induction of microthrombosis or the progression of hemorrhagic brain lesions. Multiple hypotheses have been proposed to explain this phenomenon, including the release of tissue factor, disseminated intravascular coagulation, hyperfibrinolysis, hypoperfusion with protein C activation, and platelet dysfunction. The diagnosis and management of these complex patients are difficult given the lack of understanding of the underlying mechanisms. The goal of this review is to summarize the current knowledge regarding the mechanisms of coagulopathy after blunt traumatic brain injury. The current and emerging diagnostic tools, radiological findings, treatment options, and prognosis are discussed. PMID- 22307069 TI - Association of type 2 diabetes susceptibility loci with one-year weight loss in the look AHEAD clinical trial. AB - The importance of lifestyle intervention for the prevention and treatment of type 2 diabetes (T2D) has been underscored by the limited benefit of pharmacologic therapies. We sought to determine whether genetic variants that contribute to T2D risk modify the response of weight and waist circumference to an intensive lifestyle intervention (ILI) in patients with obesity and T2D. Look AHEAD (Action for Health in Diabetes) is a randomized clinical trial comparing an ILI with a control condition on the risk of cardiovascular disease in overweight adults with T2D. We analyzed 28 single-nucleotide polymorphisms (SNPs) at/near 17 T2D susceptibility genes in 3,903 consented participants. We genetically characterized the cohort by assessing whether T2D-susceptibility loci were overrepresented compared with a nondiabetic community-based cohort (N = 1,016). We evaluated the association of individual variants and a composite genetic risk score (GRS) with anthropometric traits at baseline and after 1-year of intervention. Look AHEAD subjects carried more T2D-susceptibility alleles than the control population. At baseline, TCF7L2 risk alleles and the highest GRS were associated with lower BMI and waist circumference. Nominally significant genotype by-intervention interactions were detected for 1-year change in waist circumference with JAZF1, MTNR1B, and IRS1, and BMI with JAZF1. Highest GRS was associated with a greater reduction in waist circumference at year 1, although the variance in change attributable to the GRS was small. This study shows that the genetic burden associated with T2D risk does not undermine the effect of lifestyle intervention and suggests the existence of additional genomic regions, distinct from the T2D-susceptibility loci, which may enhance or mitigate weight loss. PMID- 22307075 TI - Cervical central canal occlusion induces noncommunicating syringomyelia. AB - BACKGROUND: Mechanisms underlying the development of noncommunicating syringomyelia are poorly understood. OBJECTIVE: To assess the influence of focal arachnoiditis and central canal (CC) occlusion (CCO) on the formation of noncommunicating syringomyelia in the adult rat cervical spinal cord. Expression of pericanalicular aquaporin-4 is also examined. METHODS: Sprague-Dawley rats were subjected to circumferential or dorsal arachnoiditis (n = 34). Rats undergoing CCO (n = 69) were divided into 4 groups: group A, kaolin injection at a single site in the dorsal columns near the CC; group B, kaolin injection at multiple sites in the dorsal columns near the CC; group C, saline injection at multiple sites in the dorsal columns near the CC; or group D, controls. Rats were killed at 1, 4, 8, and 12 weeks. The CC area and aquaporin-4 (AQP4) expression were measured at the level of maximal CC enlargement. RESULTS: Circumferential and dorsal arachnoiditis induced a mild increase in the CC area at 12 weeks. Single-site CCO induced slight CC enlargement. In contrast, multiple sites of CCO in proximity frequently induced a major expansion of the CC area (up to 50 times). Increased AQP4 expression was observed in pericanalicular astrocytes proportional to the degree of CC expansion. CONCLUSION: Multiple sites of CCO created a model of noncommunicating syringomyelia in adult rats. Increased astrocytic AQP4 expression was proportional to the degree of CC expansion. Modulation of aquaporin expression may be a novel target for therapeutic interventions to prevent syringomyelia. PMID- 22307076 TI - Novel identification of the ETS-1 splice variants p42 and p27 in prostate cancer cell lines. AB - ETS-1 is involved in cellular functions such as proliferation, migration, invasion, apoptosis and angiogenesis. The ETS-1 gene encodes three distinct proteins, ETS-1 p51 encoded by a full-length mRNA, ETS-1 p42 and ETS-1 p27 encoded by an alternatively spliced mRNA lacking exon VII and exons III-VI, respectively. ETS-1 p51, commonly considered to be the active form, has been studied in prostate cancer (PCa). However, the ETS-1 p42 and p27 variants have not yet been identified in PCa. Therefore, we aimed in this study at investigating whether the splice variants p42 and p27 are expressed in the androgen-dependent VCaP and LNCaP and the androgen-independent PC3 and DU-145 PCa cell lines. Using RT-PCR, we found the expression of both splice variants p42 and p27 at the mRNA level in the VCaP, LNCaP, PC3 and DU-145 PCa cell lines. We then confirmed the expression of ETS-1 p51 and its splice variants p42 and p27 at the protein level using an anti-ETS-1 antibody directed against the DNA-binding domain (DBD) in lysates prepared from the latter-mentioned cell lines, as well as in PC3 cell nuclear extract. Moreover, differences in the expression ratios of the ETS-1 splice variants within each cell line were also found. In conclusion, we have demonstrated for the first time the novel identification of the ETS-1 splice variants p42 and p27 in PCa cell lines. It is very likely that the role of ETS-1 p51 in PCa is significantly influenced by the presence of its splice variants ETS-1 p42 and p27 as competition, abundance, affinity, interactions and cross-talk among them will eventually determine the genes that will be targeted and subsequently affect cellular functions. Follow-up studies will need to address in functional terms, the roles of these splice variants in PCa cell lines, as well as their expression in PCa tissues and its correlation with clinical outcome. PMID- 22307077 TI - A general and selective copper-catalyzed reduction of secondary amides. AB - In situ-generated cationic copper/pybox catalyst systems allow for the selective reduction of secondary amides into the corresponding amines under mild conditions. This novel protocol has a wide substrate scope and shows good functional group tolerance. PMID- 22307078 TI - Arthroscopic debridement versus refixation of the acetabular labrum associated with femoroacetabular impingement: mean 3.5-year follow-up. AB - BACKGROUND: The acetabular labrum provides a sealing function and a degree of hip joint stability. Limited, short-term follow-up studies suggest that labral refixation/preservation leads to superior outcomes compared with labral debridement/excision. PURPOSE: To compare the results of labral refixation versus focal labral excision/debridement in a cohort of patients who underwent arthroscopic correction of femoroacetabular impingement (FAI). STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: We reported on patients who underwent labral debridement/focal labral excision during a period before the development of labral repair techniques. Patients with labral tears thought to be repairable with our current arthroscopic technique were compared with a cohort of patients who underwent labral refixation. To better match the 2 groups, only patients with labral pincer- or combined-type FAI were included. In the first 44 hips, the labrum was focally excised/debrided (group 1); in the next 50 hips, the labrum was refixed (group 2). Outcomes were measured with the modified Harris Hip Score (HHS), Short Form 12 (SF-12), and a visual analog scale (VAS) for pain preoperatively and postoperatively. Preoperative and postoperative radiographs were obtained to evaluate bony resection. RESULTS: The mean age was 32 years in group 1 and 28 years in group 2 with a mean follow-up of 42 months (range, 24-72 months). Preoperative mean subjective outcome scores were not significantly different between groups. At a mean 3.5 years' follow-up, subjective outcomes were significantly improved (P < .01) for both groups compared with preoperative scores. The HHS (P = .001), SF-12 (P = .041), and VAS pain scores (P = .004) were all significantly better for the refixation group compared with the debridement group at the most recent follow-up. At a mean 3.5 years' follow-up, good to excellent results were noted in 68% of the focal excision/debridement group and 92% of the refixation group (P = .004). CONCLUSION: Although other factors may have influenced these results, labral refixation compared with an earlier cohort of focal labral excision/debridement resulted in better HHS, SF-12, and VAS pain outcomes and a greater percentage of good to excellent results at a mean 3.5-year follow-up. PMID- 22307079 TI - Clinical and radiographic outcomes after arthroscopic repair of massive rotator cuff tears using a suture bridge technique: assessment of repair integrity on magnetic resonance imaging. AB - BACKGROUND: High retear rates of arthroscopic massive rotator cuff repair have been reported with relatively satisfactory functional outcomes. PURPOSE: To assess the clinical and radiological outcomes of an arthroscopic repair of massive rotator cuff tears using a suture bridge technique. We also aimed to explore the various factors that may affect retears. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Sixty-six patients included in the study were divided into 2 groups according to the presence of retears on magnetic resonance imaging (MRI) evaluation at a minimum of 1 year after surgery. We evaluated the visual analog scale (VAS) for pain during motions, the University of California, Los Angeles (UCLA) score, and the absolute and relative Constant scores (mean follow-up, 25.4 months). RESULTS: Twenty-eight of the 66 patients (42.4%) in this study had a retear. At the final follow-up visit, pain VAS, UCLA score, and absolute and relative Constant scores in the completely healed group were significantly superior to those in the retear group, with 2, 29.5, 76.0, and 95.2 points and 4, 26.0, 70.6, and 87.3 points, respectively (P < .05). From univariate analysis, the preoperative mean acromiohumeral distance, extent of retraction, and degree of fatty infiltration of the supraspinatus and infraspinatus were significantly different between the completely healed (7.83 mm, 2.97 cm, 1.74, and 0.71, respectively) and the retear group (6.36 mm, 3.97 cm, 2.54, and 2.07, respectively; P < .05). From multivariate logistic regression analysis, the preoperative degree of fatty infiltration of the infraspinatus and extent of retraction were the 2 most important factors associated with retears. CONCLUSION: Arthroscopic repair of massive rotator cuff tears using a suture bridge technique has a relatively high retear rate, and these structural failures appear to have a significant difference in clinical outcomes compared with the healed group. Degree of fatty infiltration of the infraspinatus and extent of retraction are the 2 most important factors associated with a retear. Orthopaedic surgeons should predict the possibility of retear before surgery and counsel patients about their expected functional results. PMID- 22307080 TI - Prediction of the graft size of 4-stranded semitendinosus tendon and 4-stranded gracilis tendon for anterior cruciate ligament reconstruction: a Chinese Han patient study. AB - BACKGROUND: Little information is available regarding parameters that would enable a surgeon to predict the size and length of 4-stranded semitendinosus (ST) and 4-stranded gracilis tendon (GT) grafts. PURPOSE: To evaluate whether certain preoperative anthropometric data enable prediction of the size of 4-stranded ST and GT autograft for anterior cruciate ligament (ACL) reconstruction. STUDY DESIGN: Cohort study (prevalence); Level of evidence, 2. METHODS: This study involved 235 Chinese Han patients who underwent double-bundle ACL reconstruction with 4-stranded autogenous ST and GT grafts. Preoperatively, the authors recorded height, weight, body mass index (BMI), gender, age, and sports activity. During surgery, the usable length of the ST and GT and the diameter of the 4-stranded grafts made of ST and GT were measured. Multiple regression analysis was used to determine relationships between anthropometric measurements and the length and diameter of intraoperatively measured ST and GT grafts. RESULTS: Strongest correlations for ST and GT length and GT graft diameter were height and weight. The strongest correlations for ST graft diameter were gender and weight. Body mass index had only moderate correlations with ST and GT graft size. Self reported activity level was not correlated. Women had significantly smaller GT and ST graft diameters and shorter tendon lengths than did men. Semitendinosus graft size was significantly larger and longer than was the GT graft (7.4 +/- 0.7 mm vs 5.9 +/- 0.6 mm and 279.9 +/- 20.8 mm vs 251.5 +/- 20.8 mm, respectively). Simple regression analysis demonstrated that height, weight, and BMI can be used to predict ST and GT autograft length and diameter. CONCLUSION: Several preoperative anthropometric measurements showed correlation with the length of the ST and GT and diameter of 4-stranded ST and GT grafts. The current data may provide surgeons with important preoperative information about size of ST and GT grafts and would be useful for patient counseling and alternative graft source planning. PMID- 22307081 TI - Distribution of bone mineral density at osteochondral donor sites in the patellofemoral joint among baseball players and controls. AB - BACKGROUND: To theoretically minimize complications of osteochondral graft harvest from the knee, grafts should be obtained from the site of lowest stress distribution across the joint. HYPOTHESIS: Long-term stress distribution over the patellofemoral (PF) joint surface is not equal in athletes. STUDY DESIGN: Cross sectional study; Level of evidence, 3. METHODS: Measurement of subchondral bone density can determine long-term resultant stress acting on an articular surface in living joints. Our analysis was performed using computed tomography (CT) image data obtained from bilateral knees of 10 college baseball fielders (fielder group) and 10 college baseball pitchers (pitcher group) and 2 control groups, including 10 college soccer players (soccer group) and 10 nonathletes (nonathlete group). The distribution pattern of subchondral bone density throughout the articular surface of the PF joint was assessed using the CT osteoabsorptiometry method. The quantitative analysis focused on the location of the low-density area at the articular surface to assess potential osteochondral donor sites. RESULTS: All participants in the pitcher and fielder groups demonstrated a low-density area widely distributed in the proximal part of the lateral trochlea. On the other hand, a high-density area was located in the distal part of the lateral notch, of the medial notch, and of the medial trochlea. No apparent differences in the distribution pattern were found between the baseball groups and the control groups. CONCLUSION: Our analysis, based on CT osteoabsorptiometry, indicates that the proximal lateral trochlea of the distal femur has the highest percentage area of low bone density at the PF joint level in donor knees of baseball players, soccer players, and nonathlete controls. CLINICAL RELEVANCE: From a biomechanical viewpoint, the proximal lateral trochlea is the optimal site for harvesting osteochondral grafts in performing mosaicplasty for baseball players. This selection for the donor site may minimize postoperative PF joint symptoms. PMID- 22307082 TI - O-GlcNAcylation of TAB1 modulates TAK1-mediated cytokine release. AB - Transforming growth factor (TGF)-beta-activated kinase 1 (TAK1) is a key serine/threonine protein kinase that mediates signals transduced by pro inflammatory cytokines such as transforming growth factor-beta, tumour necrosis factor (TNF), interleukin-1 (IL-1) and wnt family ligands. TAK1 is found in complex with binding partners TAB1-3, phosphorylation and ubiquitination of which has been found to regulate TAK1 activity. In this study, we show that TAB1 is modified with N-acetylglucosamine (O-GlcNAc) on a single site, Ser395. With the help of a novel O-GlcNAc site-specific antibody, we demonstrate that O GlcNAcylation of TAB1 is induced by IL-1 and osmotic stress, known inducers of the TAK1 signalling cascade. By reintroducing wild-type or an O-GlcNAc-deficient mutant TAB1 (S395A) into Tab1(-/-) mouse embryonic fibroblasts, we determined that O-GlcNAcylation of TAB1 is required for full TAK1 activation upon stimulation with IL-1/osmotic stress, for downstream activation of nuclear factor kappaB and finally production of IL-6 and TNFalpha. This is one of the first examples of a single O-GlcNAc site on a signalling protein modulating a key innate immunity signalling pathway. PMID- 22307083 TI - Arabidopsis E2FA stimulates proliferation and endocycle separately through RBR bound and RBR-free complexes. AB - Post-embryonic growth in plants depends on the continuous supply of undifferentiated cells within meristems. Proliferating cells maintain their competence for division by active repression of differentiation and the associated endocycle entry. We show by upregulation and downregulation of E2FA that it is required for maintaining proliferation, as well as for endocycle entry. While E2FB-RBR1 (retinoblastoma-related protein 1) complexes are reduced after sucrose addition or at elevated CYCD3;1 levels, E2FA maintains a stable complex with RBR1 in proliferating cells. Chromatin immunoprecipitation shows that RBR1 binds in the proximity of E2F promoter elements in CCS52A1 and CSS52A2 genes, central regulators for the switch from proliferation to endocycles. Overexpression of a truncated E2FA mutant (E2FA(DeltaRB)) lacking the RBR1 binding domain interferes with RBR1 recruitment to promoters through E2FA, leading to decreased meristem size in roots, premature cell expansion and hyperactivated endocycle in leaves. E2F target genes, including CCS52A1 and CCS52A2, are upregulated in E2FA(DeltaRB) and e2fa knockout lines. These data suggest that E2FA in complex with RBR1 forms a repressor complex in proliferating cells to inhibit premature differentiation and endocycle entry. Thus, E2FA regulates organ growth via two distinct, sequentially operating pathways. PMID- 22307084 TI - Insights into Chi recognition from the structure of an AddAB-type helicase nuclease complex. AB - In bacterial cells, processing of double-stranded DNA breaks for repair by homologous recombination is dependent upon the recombination hotspot sequence Chi and is catalysed by either an AddAB- or RecBCD-type helicase-nuclease. Here, we report the crystal structure of AddAB bound to DNA. The structure allows identification of a putative Chi-recognition site in an inactivated helicase domain of the AddB subunit. By generating mutant protein complexes that do not respond to Chi, we show that residues responsible for Chi recognition are located in positions equivalent to the signature motifs of a conventional helicase. Comparison with the related RecBCD complex, which recognizes a different Chi sequence, provides further insight into the structural basis for sequence specific ssDNA recognition. The structure suggests a simple mechanism for DNA break processing, explains how AddAB and RecBCD can accomplish the same overall reaction with different sets of functional modules and reveals details of the role of an Fe-S cluster in protein stability and DNA binding. PMID- 22307085 TI - Coordination of multiple enzyme activities by a single PCNA in archaeal Okazaki fragment maturation. AB - Chromosomal DNA replication requires one daughter strand-the lagging strand-to be synthesised as a series of discontinuous, RNA-primed Okazaki fragments, which must subsequently be matured into a single covalent DNA strand. Here, we describe the reconstitution of Okazaki fragment maturation in vitro using proteins derived from the archaeon Sulfolobus solfataricus. Six proteins are necessary and sufficient for coupled DNA synthesis, RNA primer removal and DNA ligation. PolB1, Fen1 and Lig1 provide the required catalytic activities, with coordination of their activities dependent upon the DNA sliding clamp, proliferating cell nuclear antigen (PCNA). S. solfataricus PCNA is a heterotrimer, with each subunit having a distinct specificity for binding PolB1, Fen1 or Lig1. Our data demonstrate that the most efficient coupling of activities occurs when a single PCNA ring organises PolB1, Fen1 and Lig1 into a complex. PMID- 22307086 TI - A role for alpha-adducin (ADD-1) in nematode and human memory. AB - Identifying molecular mechanisms that underlie learning and memory is one of the major challenges in neuroscience. Taken the advantages of the nematode Caenorhabditis elegans, we investigated alpha-adducin (add-1) in aversive olfactory associative learning and memory. Loss of add-1 function selectively impaired short- and long-term memory without causing acquisition, sensory, or motor deficits. We showed that alpha-adducin is required for consolidation of synaptic plasticity, for sustained synaptic increase of AMPA-type glutamate receptor (GLR-1) content and altered GLR-1 turnover dynamics. ADD-1, in a splice form- and tissue-specific manner, controlled the storage of memories presumably through actin-capping activity. In support of the C. elegans results, genetic variability of the human ADD1 gene was significantly associated with episodic memory performance in healthy young subjects. Finally, human ADD1 expression in nematodes restored loss of C. elegans add-1 gene function. Taken together, our findings support a role for alpha-adducin in memory from nematodes to humans. Studying the molecular and genetic underpinnings of memory across distinct species may be helpful in the development of novel strategies to treat memory related diseases. PMID- 22307087 TI - Reversible phosphocholination of Rab proteins by Legionella pneumophila effector proteins. AB - The Legionella pneumophila protein AnkX that is injected into infected cells by a Type IV secretion system transfers a phosphocholine group from CDP-choline to a serine in the Rab1 and Rab35 GTPase Switch II regions. We show here that the consequences of phosphocholination on the interaction of Rab1/Rab35 with various partner proteins are quite distinct. Activation of phosphocholinated Rabs by GTP/GDP exchange factors (GEFs) and binding to the GDP dissociation inhibitor (GDI) are strongly inhibited, whereas deactivation by GTPase activating proteins (GAPs) and interactions with Rab-effector proteins (such as LidA and MICAL-3) are only slightly inhibited. We show that the Legionella protein lpg0696 has the ability to remove the phosphocholine group from Rab1. We present a model in which the action of AnkX occurs as an alternative to GTP/GDP exchange, stabilizing phosphocholinated Rabs in membranes in the GDP form because of loss of GDI binding ability, preventing interactions with cellular GTPase effectors, which require the GTP-bound form. Generation of the GTP form of phosphocholinated Rab proteins cannot occur due to loss of interaction with cellular GEFs. PMID- 22307088 TI - Akt-dependent Skp2 mRNA translation is required for exiting contact inhibition, oncogenesis, and adipogenesis. AB - The requirement of Akt for cell proliferation and oncogenesis is mammalian target of rapamycin complex 1 (mTORC1) dependent. SV40 large T expression in Akt deficient cells restores cell proliferation rate, but is insufficient for exiting contact inhibition and oncogene-induced anchorage-independent growth, because of a failure to promote Skp2 mRNA translation. Skp2 mRNA and protein are induced upon exiting contact inhibition, which enables entry into mitosis. While Skp2 mRNA is induced in Akt-deficient cells, it is not translated, preventing entry into mitosis. Restoring Skp2 expression in Akt-deficient cells is sufficient to restore exit from contact inhibition and oncogenesis. Skp2 mRNA translation is dependent on mTORC1 and the eukaryotic translation initiation factor 4E (eIF4E). Thus, the requirement of Akt for exiting contact inhibition is mediated by the induction of Skp2 mRNA translation in eIF4E-dependent mechanism. These results provide a new insight into the role of the Akt/mTORC1/eIF4E axis in tumourigenesis. Akt-dependent Skp2 mRNA translation is also required for mitotic clonal expansion (MCE)--the earliest event in adipogenesis. Skp2 re-expression in Akt-deficient preadipocytes, which are impaired in adipogenesis, is sufficient to restore adipogenesis. These results uncover the mechanism by which Akt mediates adipogenesis. PMID- 22307089 TI - The magic and mystery of microRNA-27 in atherosclerosis. AB - Atherosclerosis (As) is now widely appreciated to represent a chronic inflammatory reaction of the vascular wall in response to dyslipidemia and endothelial distress involving the inflammatory recruitment of leukocytes and the activation of resident vascular cells. MicroRNAs (miRNAs) are a group of endogenous, small (~22 nucleotides in length) non-coding RNA molecules, which function specifically by base pairing with mRNA of genes, thereby induce translation repressions of the genes within metazoan cells. Recently, the function of miR-27, one of the miRNAs, in the initiation and progression of atherosclerosis has been identified. In vivo and in vitro studies suggest that miR-27 may serve as a diagnostic and prognostic marker for atherosclerosis. More recently, studies have identified important roles for miR-27 in angiogenesis, adipogenesis, inflammation, lipid metabolism, oxidative stress, insulin resistance and type 2 diabetes, etc. In this review, we focus on the role of miR 27 in the development of vulnerable atherosclerotic plaques, potential as a disease biomarker and novel therapeutic target in atherosclerosis. PMID- 22307090 TI - In vitro modulatory effects of flavonoids on human cytochrome P450 2C8 (CYP2C8). AB - The inhibitory effects of five flavonoids with distinct chemical classes (flavones [luteolin], flavonols [quercetin and quercitrin], and flavanones [hesperetin and hespiridin]) on cDNA-expressed CYP2C8 were investigated. CYP2C8 was co-expressed with NADPH-cytochrome P450 reductase in Escherichia coli and used to characterise potency and mechanism of these flavonoids on the isoform. Tolbutamide 4-methylhydroxylase, a high-performance liquid chromatography-based assay, was selected as marker activity for CYP2C8. Our results indicated that the flavonoids inhibited CYP2C8 with different potency. The order of inhibitory activities was quercetin > luteolin > hesperetin > hesperidin > quercitrin. All of these compounds however exhibited mechanism-based inhibition. A number of structural factors were found to be important for inhibition; these include the molecular shape (volume to surface ratio), the number of hydroxyl groups as well as glycosylation of the hydroxyl group. Quercetin was the most potent inhibitor among the flavonoids examined in this study, and our data suggest that it should be examined for potential pharmacokinetic drug interactions pertaining to CYP2C8 substrates in vivo. PMID- 22307091 TI - Reaction of the m-THPC triplet state with the antioxidant Trolox and the anesthetic Propofol: modulation of photosensitization mechanisms relevant to photodynamic therapy? AB - Antioxidants may affect the outcome of photodynamic therapy (PDT) through the inactivation of reactive oxygen species. Their direct interaction with photosensitizers excited at the triplet state is also worthy of interest. This process is investigated by laser flash photolysis of m-THPC (meso-tetra(3 hydroxyphenyl)chlorin, Foscan) hydroalcoholic solutions added with Trolox (TrOH), a standard antioxidant or Propofol (PfOH, Diprivan((r))), a common anesthetic agent also characterized for its antioxidant properties. Transient UV-visible absorption spectra, kinetics at selected wavelengths and final spectra after extensive laser irradiation show that both compounds react with the m-THPC triplet state, (3)m-THPC, to ultimately restore the photosensitizer in its ground state. For PfOH, this process mainly appears as a single step obeying pseudo first order kinetics. The bimolecular rate constant for the quenching of (3)m THPC by PfOH is around 2 * 10(6) M(-1) s(-1), a value increased to some extent by the water content of the solution. A bimolecular reaction between (3)m-THPC and TrOH is observed with a rate constant of similar magnitude and dependence upon water. However, the reaction leads, at least partly, to intermediate species assigned to the TrO radical and the m-THPC anion radical. Within a few ms, these species back react to yield m-THPC in its ground state. A general mechanism involving an intermediate activated complex with some charge transfer character is proposed. Depending on the redox potentials for the oxidation of the antioxidant, this complex evolves predominantly either toward the formation of radicals (TrOH) or back to the photosensitizer ground state (PfOH). Notably, the kinetics data suggest that Propofol may quench (3)m-THPC at concentrations relevant of clinical situation in PDT involving anesthesia. PMID- 22307092 TI - Supraglottic Airway Device preference and insertion speed in F1 doctors. PMID- 22307093 TI - Overview of supportive care in patients receiving chemotherapy: antiemetics, pain management, anemia, and neutropenia. AB - With advancements in the field of oncology, more and more people are living with cancer. The prevalence of invasive cancer in the United States is estimated to be almost 12 million. The treatment of cancer as well as the malignancy itself can cause an immense number of side effects and other complications. This article explores the fundamentals of supportive care in patients receiving chemotherapy and radiation treatment including prevention of nausea and vomiting, pain management, treatment of anemia and neutropenia. Proper supportive care can help improve clinical outcomes, reduce medical costs, and help patients with cancer live longer, happier, and healthier lives. For these reasons, it is important for pharmacists to possess a solid understanding of how to prevent and treat the adverse effects of chemotherapy and radiation treatment. PMID- 22307094 TI - A faculty-led mock residency interview exercise for fourth-year doctor of pharmacy students. AB - PURPOSE: To determine whether a faculty-led mock-interview activity enhanced pharmacy student preparation for the residency interview process and increased match rates. METHODS: Twenty-eight doctor of pharmacy students volunteered for a 40-minute mock-interview session with 2-person faculty teams. A standard roster of 12 interview questions was derived from published literature and the faculty members' experience. Feedback on the student's interview performance was provided verbally during the session. Following the interview, students were given a 2 part survey instrument. The first part of the survey was administered immediately following the mock-interview session and the second part was administered after the standard date for residency program results (known as "Match Day"). Participant match rates were compared to American Society of Health-System Pharmacists (ASHP) national rates. RESULTS: 82.5% (23 of 27) of students in the mock-interview group matched a postgraduate year 1 (PGY1) program. Compared to national rates (61.9%), more students in our surveyed mock-interview group matched a PGY1 residency (P = .015; odds ratio [OR] 3.546, 95% CI 1.161-12.116). CONCLUSIONS: Higher match rates were seen in the students completing the mock residency interview compared to ASHP national rates. In general, students completing the mock interview found the process helpful and felt better prepared for their residency interviews. PMID- 22307095 TI - A cross-sectional study of glucose regulation in young adults with very low birth weight: impact of male gender on hyperglycaemia. AB - OBJECTIVES: To investigate glucose regulation in young adults with very low birth weight (VLBW; <1500 g) in an Asian population. DESIGN: Cross-sectional observational study. SETTING: A general hospital in Hamamatsu, Japan. PARTICIPANTS: 111 young adults (42 men and 69 women; aged 19-30 years) born with VLBW between 1980 and 1990. Participants underwent standard 75 g oral glucose tolerance test (OGTT). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were glucose and insulin levels during OGTT and risk factors for a category of hyperglycaemia defined as follows: diabetes mellitus, impaired glucose tolerance (IGT), impaired fasting glycaemia (IFG) and non diabetes/IGT/IFG with elevated 1 h glucose levels (>8.6 mmol/l). The secondary outcomes were the pancreatic beta cell function (insulinogenic index and homeostasis model of assessment for beta cell (HOMA-beta)) and insulin resistance (homeostasis model of assessment for insulin resistance (HOMA-IR)). RESULTS: Of 111 young adults with VLBW, 21 subjects (19%) had hyperglycaemia: one had type 2 diabetes, six had IGT, one had IFG and 13 had non-diabetes/IGT/IFG with elevated 1 h glucose levels. In logistic regression analysis, male gender was an independent risk factor associated with hyperglycaemia (OR 3.34, 95% CI 1.08 to 10.3, p=0.036). Male subjects had significantly higher levels of glucose and lower levels of insulin during OGTT than female subjects (p<0.001 for glucose and p=0.005 for insulin by repeated measures analysis of variance). Pancreatic beta cell function was lower in men (insulinogenic index: p=0.002; HOMA-beta: p=0.001), although no gender difference was found in insulin resistance (HOMA-IR: p=0.477). In male subjects, logistic regression analysis showed that small for gestational age was an independent risk factor associated with hyperglycaemia (OR 33.3, 95% CI 1.67 to 662.6, p=0.022). CONCLUSIONS: 19% of individuals with VLBW already had hyperglycaemia in young adulthood, and male gender was a significant independent risk factor of hyperglycaemia. In male young adults with VLBW, small for gestational age was associated with hyperglycaemia. PMID- 22307096 TI - Emergency and surgery services of primary hospitals in the United Republic of Tanzania. AB - OBJECTIVE: The primary objective was to evaluate the capacity of first-referral health facilities in Tanzania to perform basic surgical procedures. The intent was to assist in planning strategies for universal access to life-saving and disability-preventing surgical services. DESIGN: Cross-sectional survey. SETTING: First-referral health facilities in the United Republic of Tanzania. PARTICIPANTS: 48 health facilities. MEASURES: The WHO Tool for Situational Analysis to Assess Emergency and Essential Surgical Care was employed to capture a health facility's capacity to perform basic surgical (including obstetrics and trauma) and anaesthesia interventions by investigating four categories of data: infrastructure, human resources, interventions available and equipment. The tool queried the availability of eight types of care providers, 35 surgical interventions and 67 items of equipment. RESULTS: The 48 facilities surveyed served 18.6 million residents (46% of the population). Supplies for basic airway management were inconsistently available. Only 42% had consistent access to oxygen, and only six functioning pulse oximeters were located in all facilities surveyed. 37.5% of facilities reported both consistent running water and electricity. While very basic interventions (suturing, wound debridement, incision and drainage) were provided in nearly all facilities, more advanced life saving procedures including chest tube thoracostomy (30/48), open fracture management (29/48) and caesarean section delivery (32/48) were not consistently available. CONCLUSIONS: Based on the results in this WHO country survey, significant gaps exist in the capacity for emergency and essential surgical services in Tanzania including deficits in human resources, essential equipment and infrastructure. The information in this survey will provide a foundation for evidence-based decisions in country-level policy regarding the allocation of resources and provision of emergency and essential surgical services. PMID- 22307097 TI - Eliciting views on antibiotic prescribing and resistance among hospital and outpatient care physicians in Berlin, Germany: results of a qualitative study. AB - OBJECTIVE: To better understand physicians' views on factors of influence for the prescribing of antibiotics and on antibiotic resistance in the Berlin region, Germany. DESIGN: Qualitative study with focus groups. SETTING: Outpatient care and hospital care practice in the Berlin region, Germany. PARTICIPANTS: 7 General practitioners, two urologists, one paediatrician from outpatient care and eight internists, two paediatricians, two ear, nose and throat specialists and two urologists from hospital care. RESULTS: Physicians showed differential interest in topics related to antibiotic prescribing and antibiotic resistance. Outpatient care physicians were interested in topics around their own prescribing, such as being able to diagnose and prescribe precisely, and topics about patient demand and non-compliance. Hospital care physicians were interested in hygiene challenges, limited consult time and multi-resistant pathogens. CONCLUSIONS: Physicians considered the development of resistance to be more in the domain of clinical treatment than that of the patient. Major challenges related to antibiotic resistance for this group of physicians are access to and clarity of treatment recommendations, implementation of hygienic measures, as well as increased outsourcing of laboratory services. Results raise questions about whether meeting physicians' expectations should be a focus when developing intervention that aims to influence antibiotic resistance in this and other areas of Germany. PMID- 22307098 TI - Computerised lung sound analysis to improve the specificity of paediatric pneumonia diagnosis in resource-poor settings: protocol and methods for an observational study. AB - INTRODUCTION: WHO case management algorithm for paediatric pneumonia relies solely on symptoms of shortness of breath or cough and tachypnoea for treatment and has poor diagnostic specificity, tends to increase antibiotic resistance. Alternatives, including oxygen saturation measurement, chest ultrasound and chest auscultation, exist but with potential disadvantages. Electronic auscultation has potential for improved detection of paediatric pneumonia but has yet to be standardised. The authors aim to investigate the use of electronic auscultation to improve the specificity of the current WHO algorithm in developing countries. METHODS: This study is designed to test the hypothesis that pulmonary pathology can be differentiated from normal using computerised lung sound analysis (CLSA). The authors will record lung sounds from 600 children aged <=5 years, 100 each with consolidative pneumonia, diffuse interstitial pneumonia, asthma, bronchiolitis, upper respiratory infections and normal lungs at a children's hospital in Lima, Peru. The authors will compare CLSA with the WHO algorithm and other detection approaches, including physical exam findings, chest ultrasound and microbiologic testing to construct an improved algorithm for pneumonia diagnosis. DISCUSSION: This study will develop standardised methods for electronic auscultation and chest ultrasound and compare their utility for detection of pneumonia to standard approaches. Utilising signal processing techniques, the authors aim to characterise lung sounds and through machine learning, develop a classification system to distinguish pathologic sounds. Data will allow a better understanding of the benefits and limitations of novel diagnostic techniques in paediatric pneumonia. PMID- 22307099 TI - Anaemia and the development of depressive symptoms following acute coronary syndrome: longitudinal clinical observational study. AB - OBJECTIVE: Depressive symptoms are common following acute coronary syndrome (ACS) and predict subsequent cardiovascular morbidity. Depression in acute cardiac patients appears to be independent of clinical disease severity and other cardiovascular measures. One factor that has not been considered previously is anaemia, which is associated with fatigue and adverse cardiac outcomes. This study assessed the relationship between anaemia on admission and depressive symptoms following ACS. DESIGN: Longitudinal clinical observational study. SETTING: Coronary care unit. PATIENTS: 223 patients with documented ACS. MAIN OUTCOME MEASURES: Depressive symptoms measured with the Beck Depression Inventory 3 weeks after admission. RESULTS: Anaemia was defined with WHO criteria and was present in 30 (13.5%) patients. Anaemia predicted raised depression scores 3 weeks later independently of age, gender, marital status, educational attainment, smoking, Global Registry of Acute Cardiac Events (GRACE) risk scores, negative mood in hospital and history of depression (p=0.003). The odds of a Beck Depression Inventory score >=10 among anaemic patients were 4.03 (95% CIs 1.48 to 11.00), adjusted for covariates. Sensitivity analyses indicated that effects were also present when haemoglobin was analysed as a continuous measure. Anaemia also predicted major adverse cardiac events over the subsequent 12 months. CONCLUSIONS: Anaemia appears to contribute to depression following ACS and is associated with future cardiac morbidity. Studies evaluating the effects of anaemia management will help delineate the role of this pathway more precisely. PMID- 22307100 TI - Short sleep and obesity in a large national cohort of Thai adults. AB - OBJECTIVE: To investigate the relationship between short sleep and obesity among Thai adults. DESIGN: Both 4-year longitudinal and cross-sectional analyses of a large national cohort. SETTING: Thai adults residing nationwide from 2005 to 2009. PARTICIPANTS: Cohort members were enrolled as distance learners at Sukhothai Thammathirat Open University (N=87 134 in 2005 and 60 569 at 2009 follow-up). At 2005 baseline, 95% were between 20 and 49 years of age. MEASURES: Self-reported sleep duration was categorised as <6, 6, 7, 8 and >=9 h. For all analyses (2005 and 2009 cross-sectional and 2005-2009 longitudinal), we used multinomial logistic regression models to assess the effect of sleep duration on abnormal body size (underweight, overweight-at-risk, obese). Results were adjusted for an array of relevant covariates. RESULTS: At the last cohort follow up in 2009, cross-sectional associations linked short sleep (<6 h) and obesity: adjusted ORs (AOR) =1.49, 95% CIs 1.32 to 1.68 for women and AOR=1.36, 95% CI 1.21 to 1.52 for men. The earlier cross-sectional baseline results in 2005 were quite similar. Longitudinal analysis (2005-2009) of 4-year incremental weight gain (5 to <10%, 10 to <20% and 20%+) strongly supported the short sleep-obesity relationship (significant AORs of 1.10, 1.30 and 1.69, respectively). CONCLUSIONS: The results are internally consistent (2005 and 2009) and longitudinally confirmatory of a short sleep effect on obesity among Thai adults. Further research is needed to elucidate causal mechanisms underlying the sleep obesity relationship. PMID- 22307101 TI - Lifestyle counselling targeting infant's mother during the child's first year and offspring weight development until 4 years of age: a follow-up study of a cluster RCT. AB - OBJECTIVE: To investigate the effect of intensified lifestyle counselling targeting infants' mothers on offspring weight development during the first 4 years of life. DESIGN AND SETTING: Follow-up of a cluster-randomised controlled trial in primary care child health clinics during 2004-2006 in Finland. Participants received a follow-up survey during 2010 concerning weight and height measurements of their offspring. Number of clusters was six and the response rate to the follow-up 71.9% (N=64/89). PARTICIPANTS: The participants (N=89) were mothers of infants aged 2-10 months. INTERVENTION: The intervention included individual counselling on diet and physical activity when the infant was 2-10 months of age and an option to attend supervised group exercise sessions. PRIMARY AND SECONDARY OUTCOME MEASURES: The authors analysed the secondary outcome of the intervention study: the weight development of the offspring. The primary outcome was the proportion of women returning to their prepregnancy weight by 10 months post partum, reported earlier. RESULTS: Multilevel mixed effect non-linear regression models included group, age of the child and interaction between group and age of the child. The increase of BMI z-score between 24 and 48 months was slower among the intervention group offspring (-0.034 to -0.002, p=0.028) as compared with control group. Z-scores for weight-for-length/height did not differ between groups when the period 0-48 months was analysed (p=0.23) but for the period of 24-48 months, between-group differences were significant (p=0.012). CONCLUSIONS: Lifestyle counselling targeting mothers during the child's first year may be effective in slowing offspring weight gain until 4 years of age. However, larger studies are needed to confirm the findings which may have the potential in combatting the obesity epidemic. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN21512277. PMID- 22307102 TI - A prospective follow-up study of the association of radiation exposure with fatal and non-fatal stroke among atomic bomb survivors in Hiroshima and Nagasaki (1980 2003). AB - OBJECTIVE: Use of medical radiotherapy has increased markedly in recent decades. Whether the consequence includes an increased risk of cardiovascular disease remains to be determined. The purpose of this study was to examine the association between radiation exposure and the incidence of stroke among Japanese atomic bomb survivors. DESIGN: A prospective follow-up study. SETTING AND PARTICIPANTS: Radiation exposure from the atomic bombing was assessed in 9515 subjects (34.8% men) with 24-year follow-up from 1980. Subjects were free of prevalent stroke when follow-up began. OUTCOME MEASURES: Stroke events and the underlying cause of death were reviewed to confirm the first-ever stroke. Subtypes (ischaemic and haemorrhagic events) were categorised based on established criteria according to the definitions of typical/atypical stroke symptoms. RESULTS: Overall mean radiation dose (+/-SD) in units of gray (Gy) was 0.38+/-0.58 (range: 0-3.5). During the study period, 235 haemorrhagic and 607 ischaemic events were identified. For men, after adjusting for age and concomitant risk factors, the risk of haemorrhagic stroke rose consistently from 11.6 to 29.1 per 10 000 person-years as doses increased from <0.05 to >=2 Gy (p=0.009). Incidence also rose within the dose range <1 Gy (p=0.004) with no dose threshold. In women, the risk of haemorrhagic stroke rose with increasing radiation exposure but not until doses reached a threshold of 1.3 Gy (95% CI 0.5 to 2.3). Among women, for doses <1.3 Gy, differences in stroke risk were modest (13.5 per 10 000 person-years), while it increased to 20.3 per 10 000 person years for doses that ranged from 1.3 to <2.2 Gy and to 48.6 per 10 000 person years for doses that were higher (p=0.002). In both sexes, dose was unrelated to ischaemic stroke. CONCLUSION: While the risk of haemorrhagic stroke increases with rising radiation exposure for both sexes, effects in women are less apparent until doses exceed a threshold at 1.3 Gy. PMID- 22307103 TI - Detecting and measuring deprivation in primary care: development, reliability and validity of a self-reported questionnaire: the DiPCare-Q. AB - OBJECTIVES: Advances in biopsychosocial science have underlined the importance of taking social history and life course perspective into consideration in primary care. For both clinical and research purposes, this study aims to develop and validate a standardised instrument measuring both material and social deprivation at an individual level. METHODS: We identified relevant potential questions regarding deprivation using a systematic review, structured interviews, focus group interviews and a think-aloud approach. Item response theory analysis was then used to reduce the length of the 38-item questionnaire and derive the deprivation in primary care questionnaire (DiPCare-Q) index using data obtained from a random sample of 200 patients during their planned visits to an ambulatory general internal medicine clinic. Patients completed the questionnaire a second time over the phone 3 days later to enable us to assess reliability. Content validity of the DiPCare-Q was then assessed by 17 general practitioners. Psychometric properties and validity of the final instrument were investigated in a second set of patients. The DiPCare-Q was administered to a random sample of 1898 patients attending one of 47 different private primary care practices in western Switzerland along with questions on subjective social status, education, source of income, welfare status and subjective poverty. RESULTS: Deprivation was defined in three distinct dimensions: material (eight items), social (five items) and health deprivation (three items). Item consistency was high in both the derivation (Kuder-Richardson Formula 20 (KR20) =0.827) and the validation set (KR20 =0.778). The DiPCare-Q index was reliable (interclass correlation coefficients=0.847) and was correlated to subjective social status (r(s)=-0.539). CONCLUSION: The DiPCare-Q is a rapid, reliable and validated instrument that may prove useful for measuring both material and social deprivation in primary care. PMID- 22307104 TI - Evaluating the travel, physical activity and carbon impacts of a 'natural experiment' in the provision of new walking and cycling infrastructure: methods for the core module of the iConnect study. AB - INTRODUCTION: Improving infrastructure to support walking and cycling is often regarded as fundamental to encouraging their widespread uptake. However, there is little evidence that specific provision of this kind has led to a significant increase in walking or cycling in practice, let alone wider impacts such as changes in overall physical activity or carbon emissions. Connect2 is a major new project that aims to promote walking and cycling in the UK by improving local pedestrian and cycle routes. It therefore provides a useful opportunity to contribute new evidence in this field by means of a natural experimental study. METHODS AND ANALYSIS: iConnect is an independent study that aims to integrate the perspectives of public health and transport research on the measurement and evaluation of the travel, physical activity and carbon impacts of the Connect2 programme. In this paper, the authors report the study design and methods for the iConnect core module. This comprised a cohort study of residents living within 5 km of three case study Connect2 projects in Cardiff, Kenilworth and Southampton, supported by a programme of qualitative interviews with key informants about the projects. Participants were asked to complete postal questionnaires, repeated before and after the opening of the new infrastructure, which collected data on demographic and socioeconomic characteristics, travel, car fuel purchasing and physical activity, and potential psychosocial and environmental correlates and mediators of those behaviours. In the absence of suitable no-intervention control groups, the study design drew on heterogeneity in exposure both within and between case study samples to provide for a counterfactual. ETHICS AND DISSEMINATION: The study was approved by the University of Southampton Research Ethics Committee. The findings will be disseminated through academic presentations, peer-reviewed publications and the study website (http://www.iconnect.ac.uk) and by means of a national seminar at the end of the study. PMID- 22307105 TI - Empirical evidence that disease prevalence may affect the performance of diagnostic tests with an implicit threshold: a cross-sectional study. AB - OBJECTIVE: To investigate the effects that prevalence has on the diagnostic performance of junior doctors in interpreting x-rays. DESIGN: Two-armed cross sectional design using systematic sampling. SETTING: Emergency department in the UK. PARTICIPANTS: From a sample of 2593 patients (1434 men and 1159 women) taken from an unselected attending cohort between January and April 2002, 967 x-rays were analysed. The sex distribution was 558 men and 409 women, and the mean age of those receiving an x-ray was 34.6. INTERVENTIONS: The interpretation of x-rays by junior doctors after their triage into high- and low-prevalence populations by radiographers. MAIN OUTCOME MEASURES: Sensitivity, specificity, likelihood ratios, diagnostic odds ratios and receiver operator characteristic curve. RESULTS: There were statistically significant differences in the performance characteristics of junior doctors when interpreting high-probability and low probability x-rays. For the high- and low-probability populations, respectively, the sensitivities were 95.8% (95% CI 91.1% to 98.1%) and 78.3% (95% CI 65.7% to 87.2%) and the specificities were 56.0% (95% CI 41.9% to 69.2%) and 92.3% (95% CI 90.0% to 94.2%). Hierarchical logistic regression showed that the sensitivity did depend on the type of x-ray being interpreted but the diagnostic odds ratios did not vary significantly with prevalence, suggesting that doctors were changing their implicit threshold between the two populations along a common receiver operator characteristic curve. CONCLUSIONS: This study provides evidence on how the prevalence may affect the performance of diagnostic tests with an implicit threshold and potentially includes the clinical history and examination. This has implications both for clinicians applying research findings to their practice and the design of future studies. PMID- 22307106 TI - Method/basis set dependence of NICS values among metallic nano-clusters and hydrocarbons. AB - The influence of various all-electron basis sets and effective core potentials employed along with several DFT functionals (B3LYP, B3PW91, BLYP, BP86 and M06) on the magnitude of nucleus independent chemical shift (NICS) values in different metallic nano-clusters and hydrocarbons is studied. In general, it is demonstrated that the NICS values are very sensitive to the applied method/basis set; however, the method/basis set dependence is more prominent for computed NICS values in transition metal clusters. In hydrocarbons, medium-size basis sets perform roughly similar to large basis sets in most cases. It is also found that NICS(0) values are more sensitive to the method/basis set variation compared to the NICS values computed at 1 or 2 A above the ring plane. However, in many cases, no broad-spectrum regulation is found for the effect of basis set/method on the magnitude of NICS values. A detailed study showed that bond length alternation in a molecule has an insignificant effect on the magnitude of NICS values so the influence of method/basis sets on the magnitude of NICS values mostly arises from the different predicted ring current intensities at various computational levels. PMID- 22307107 TI - Hydrogen thermal desorption spectra: insights from molecular simulation. AB - Thermal desorption spectra of a number of metal-organic frameworks were studied using grand canonical Monte Carlo simulation. Our simulation results are in qualitative agreement with experimental results but also show that great care must be taken when choosing the force field to describe the hydrogen/framework interaction. As the simulations additionally yield the positions and potential energies of the adsorbed molecules it is straightforward to assign the peaks and features in the thermal desorption spectra to specific adsorption sites. We show that the location of the peaks is directly related to the hydrogen-framework interaction which is a complex function of the chemical and topological environment of the pore space, the pore size and the presence of specific interaction sites such as open metal sites. Finally, we demonstrate that an IRMOF 8 sample used to obtain an experimental thermal desorption spectrum must have indeed been catenated as previously suspected. Overall, molecular simulation is a useful tool to complement the interpretation of experimental thermal desorption spectra. PMID- 22307108 TI - The TPX2 gene is a promising diagnostic and therapeutic target for cervical cancer. AB - The target protein for Xklp2 (TPX2), a microtubule-associated protein, can be used to evaluate more precisely the proliferative behavior of tumor cells. The abnormal expression of TPX2 in various types of malignant tumors has been reported, but less is known for cervical cancer. We studied the relationship between TPX2 expression and the biological behavior of cervical cancer. Immunohistochemistry and RT-PCR were used to detect the expression of TPX2 in cervical cancer tissues. The inhibitory effect of TPX2-siRNA on the growth of HeLa human cervical carcinoma cells was studied in vitro. TPX2 expression was found to be significantly higher in cervical carcinoma compared to normal cervical tissues and CIN. The expression of TPX2 in cervical cancer was correlated with histological grading, FIGO staging and lymph node metastasis. TPX2 RNAi in HeLa cervical cancer cells caused S-phase cell cycle arrest, induced apoptosis and inhibited cell proliferation and invasion. In conclusion, TPX2 shows potential to be used as a new marker for cervical cancer diagnosis and therapy. PMID- 22307109 TI - Optical penetration-based silkworm pupa gender sensor structure. AB - This paper proposes and experimentally demonstrates for what is believed to be the first time a highly sought-after optical structure for highly-accurate identification of the silkworm pupa gender. The key idea is to exploit a long wavelength optical beam in the red or near infrared spectrum that can effectively and safely penetrate the body of a silkworm pupa. Later on, simple image processing operations via image thresholding, blob filtering, and image inversion processes are applied in order to eliminate the unwanted image noises and at the same time highlight the gender gland. Experimental proof of concept using three 636 nm wavelength light emitting diodes, a two-dimensional web camera, an 8 bit microcontroller board, and a notebook computer shows a very high 95.6% total accuracy in identifying the gender of 45 silkworm pupae with a measured fast identification time of 96.6 ms. Other key features include low cost, low component counts, and ease of implementation and control. PMID- 22307110 TI - Quality-guided orientation unwrapping for fringe direction estimation. AB - Fringe patterns produced by various optical interferometric techniques encode information such as shape, deformation, and refractive index. Denoising and demodulation are two important procedures to retrieve information from a single closed fringe pattern. Various existing denoising and demodulation techniques require fringe direction/orientation during the processing. Fringe orientation is often easier to obtain but fringe direction is needed in some demodulation techniques. A quality-guided orientation unwrapping scheme is proposed to estimate direction from orientation. Two techniques, one based on windowed Fourier ridges and the other based on fringe gradient, are proposed for the quality-guided orientation unwrapping scheme. The direction qualities are compared for both simulated and experimental fringe patterns. Their application to demodulation technique is also given. PMID- 22307111 TI - Optimization of nanotube electrode geometry in a liquid crystal media from wavefront aberrations. AB - This paper presents experimental optimization of number and geometry of nanotube electrodes in a liquid crystal media from wavefront aberrations for realizing nanophotonic devices. The refractive-index gradient profiles from different nanotube geometries--arrays of one, three, four, and five--were studied along with wavefront aberrations using Zernike polynomials. The optimizations help the device to make application in the areas of voltage reconfigurable microlens arrays, high-resolution displays, wavefront sensors, holograms, and phase modulators. PMID- 22307112 TI - Finite-difference time-domain analysis of time-resolved reflectance from an adult head model composed of multilayered slabs with a nonscattering layer. AB - Finite-difference time-domain (FDTD) analysis has been used to predict the time resolved reflectance from multilayered slabs with a nonscattering layer. Light propagation across the nonscattering layer was calculated based on the light intensity characteristics along a ray in free space. Additional equivalent source functions due to light from scattering regions across the nonscattering region were introduced into the diffusion equation and an additional set of the diffusion equation was solved by FDTD analysis by employing new boundary conditions. The formulation was used to calculate time-resolved reflectances of three- and four-layered slabs containing a nonscattering layer. The received light intensity and the mean time of flight estimated from the time-resolved reflectance are in reasonable agreement with previously reported experimental data and Monte Carlo simulations. PMID- 22307113 TI - End-to-end sensor simulation for spectral band selection and optimization with application to the Sentinel-2 mission. AB - An end-to-end sensor simulation is a proper tool for the prediction of the sensor's performance over a range of conditions that cannot be easily measured. In this study, such a tool has been developed that enables the assessment of the optimum spectral resolution configuration of a sensor based on key applications. It employs the spectral molecular absorption and scattering properties of materials that are used for the identification and determination of the abundances of surface and atmospheric constituents and their interdependence on spatial resolution and signal-to-noise ratio as a basis for the detailed design and consolidation of spectral bands for the future Sentinel-2 sensor. The developed tools allow the computation of synthetic Sentinel-2 spectra that form the frame for the subsequent twofold analysis of bands in the atmospheric absorption and window regions. One part of the study comprises the assessment of optimal spatial and spectral resolution configurations for those bands used for atmospheric correction, optimized with regard to the retrieval of aerosols, water vapor, and the detection of cirrus clouds. The second part of the study presents the optimization of thematic bands, mainly driven by the spectral characteristics of vegetation constituents and minerals. The investigation is performed for different wavelength ranges because most remote sensing applications require the use of specific band combinations rather than single bands. The results from the important "red-edge" and the "short-wave infrared" domains are presented. The recommended optimum spectral design predominantly confirms the sensor parameters given by the European Space Agency. The system is capable of retrieving atmospheric and geobiophysical parameters with enhanced quality compared to existing multispectral sensors. Minor spectral changes of single bands are discussed in the context of typical remote sensing applications, supplemented by the recommendation of a few new bands for the next generation of optical Sentinel sensors. PMID- 22307114 TI - Modal decomposition technique for multimode fibers. AB - We propose a new solution for modal decomposition in multimode fibers, based on a spectral and spatial imaging technique. The appearance of spurious modes in the spectral and spatial processing of the images at the output of the fiber under test when it has more than two modes is demonstrated theoretically. The new method, which allows us to identify spurious modes, is more accurate, simpler, and faster than previously reported methods. For demonstration, measurements in a standard step-index multimode fiber and a small-core microstructured fiber are carried out successfully. PMID- 22307115 TI - Three-dimensional shape measurement of aspheric mirrors with fringe reflection photogrammetry. AB - Three-dimensional (3D) shape measurement of an aspheric mirror with fringe reflection photogrammetry involves three steps: correspondence matching, triangulation, and bundle adjustment. Correspondence matching is realized by absolute phase tracking and triangulation is computed by the intersection of reflection and incidence rays. The main contribution in this paper is constraint bundle adjustment for carefully dealing with lens distortion in the process of ray intersection, as compared to the well-known grating reflection photogrammetry. Additionally, a free frame is proposed to alleviate troublesome system geometrical calibration, and constraint bundle adjustment is operated in the free frame to refine the 3D shape. Simulation and experiment demonstrate that constraint bundle adjustment can improve absolute measurement accuracy of aspheric mirrors. PMID- 22307116 TI - White-light interferometry on rough surfaces--measurement uncertainty caused by noise. AB - White-light interferometry on rough surfaces is an optical method for the measurement of the geometrical form of objects. The longitudinal coordinate of the measured surface is obtained from the measured interferogram by means of an evaluation method. However, the longitudinal coordinate cannot be determined completely accurately because the interferogram is affected by noise. We calculate the lower limit of the longitudinal measurement uncertainty caused by noise by use of the Cramer-Rao inequality. Additionally, we calculate the lower limit of the longitudinal measurement uncertainty caused by shot noise only. PMID- 22307117 TI - Experimental implementation of the multifunctional compact two-photon state analyzer. AB - We report on experimental implementation of a multifunctional two-photon state analyzer. The device aims to be compact and able to provide several important characteristics about any two-photon quantum state. It operates in two modes: first mode is the two-photon interference analysis giving the information about spectral properties of the photons and the degree of mutual indistinguishability. The second mode provides polarization analysis and complete two-photon state tomography. Density matrix estimated from the tomography data reveals namely the quantum state purity or negativity. This device was tested on the photon pairs generated by the Kwiat source. PMID- 22307118 TI - Talbot effect by a photorefractive volume phase grating. AB - In our proposal a light intensity distribution generated by an incoherently illuminated planar amplitude grating is projected into a photorefractive crystal. This 3D distribution is mapped as an index refractive perturbation via the photorefractive effect thereby generating a volume phase grating. The self imaging phenomenon in the Fresnel field of this volume phase grating coherently illuminated is theoretically and experimentally analyzed. A model to simulate this volume grating that considers the 3D light intensity distribution formed in the crystal combined with the photorefractive grating formation theory is proposed. A path-integral approach to calculate the self-image patterns which account for the inhomogeneous propagation through the photorefractive grating is employed. The experimental and theoretical results show that the self-images location coincides with that of the self-images generated by planar phase grating of the same period. Moreover, the self-images visibility depends on three parameters: the exit pupil diameter of the incoherent recording optical system, the external electric field applied on the crystal, and the crystal thickness. To study the visibility behavior, a phase parameter which includes the three mentioned parameters is proposed. The self-images visibility shows the typical sinusoidal dependence found in planar phase grating. A good agreement between theoretical and experimental results is observed. PMID- 22307119 TI - Determination of first-order derivative matrix of wavefront aberration with respect to system variables. AB - The first-order derivative matrix of a function with respect to a variable vector is referred to as the Jacobian matrix in mathematics. Current commercial software packages for the analysis and design of optical systems use a finite difference (FD) approximation methodology to estimate the Jacobian matrix of the wavefront aberration with respect to all of the independent system variables in a single raytracing pass such that the change of the wavefront aberration can be determined simply by computing the product of the developed Jacobian matrix and the corresponding changes in the system variables. The proposed method provides an ideal basis for automatic optical system design applications in which the merit function is defined in terms of wavefront aberration. The validity of the proposed approach is demonstrated by means of two illustrative examples. It is shown that the proposed method requires fewer iterations than the traditional FD approach and yields a more reliable and precise optimization performance. However, the proposed method incurs an additional CPU overhead in computing the Jacobian matrix of the merit function. As a result, the CPU time required to complete the optimization process is longer than that required by the FD method. PMID- 22307120 TI - Primary chromatic aberrations of a diffractive lens on finite substrate. AB - In this report, we present an analysis for the primary chromatic aberrations of a diffractive lens on a spherically curved substrate having nonunity refractive index. This analysis facilitates achieving an optimal thin lens layout during structural design of the diffractive lens with prespecified targets for primary chromatic aberrations. Sets of nomographs that provide ready estimates for these aberrations are also given. PMID- 22307121 TI - Two-dimensional mapping of the electron density in laser-produced plasmas. AB - We performed two-dimensional (2D) mapping of the electron density in a laser produced plasma with high spatial and temporal resolution. The plasma was produced by irradiating an aluminum target with 1064 nm, 6 ns pulses from a Nd:YAG laser under vacuum conditions. Stark broadening of the lines was used to estimate the electron density at various locations inside the plasma. The 2D spectral images were captured at different spatial points in the plasma using an imaging spectrograph coupled to an intensified CCD at various times during the plasma expansion. A comparison between radially averaged and radially resolved electron density profiles showed differences in the estimated values at the earlier times of plume evolution and closer distances to the target. However, the measured radially averaged values are consistent with 2D radial profiles at later times and/or farther distances from the target surface. PMID- 22307122 TI - Temporal coupled-mode theory of ring-bus-ring Mach-Zehnder interferometer. AB - The temporal coupled-mode theory (TCMT) for a ring-bus-ring Mach-Zehnder interferometer device is developed by taking energy conservation into account. The intercavity interaction in the device is facilitated via a tricoupler, which makes the decay of modes quantitatively different from that in other existing resonator schemes. The TCMT is related to the transfer matrix formalism with energy conservation and the Q factor, and it predicts results in good agreement with the experimental results. The mode analysis from the TCMT is quite illustrative because it can mimic the transparency as an electromagnetically induced transparency expression. The analysis of the tricoupler is applicable for analyzing the transparent resonance in two other similar configurations. PMID- 22307123 TI - Flat field concave holographic grating with broad spectral region and moderately high resolution. AB - In order to deal with the conflicts between broad spectral region and high resolution in compact spectrometers based on a flat field concave holographic grating and line array CCD, we present a simple and practical method to design a flat field concave holographic grating that is capable of imaging a broad spectral region at a moderately high resolution. First, we discuss the principle of realizing a broad spectral region and moderately high resolution. Second, we provide the practical method to realize our ideas, in which Namioka grating theory, a genetic algorithm, and ZEMAX are used to reach this purpose. Finally, a near-normal-incidence example modeled in ZEMAX is shown to verify our ideas. The results show that our work probably has a general applicability in compact spectrometers with a broad spectral region and moderately high resolution. PMID- 22307124 TI - Speckle orientation in paraxial optical systems. AB - The statistical properties of speckles in paraxial optical systems depend on the system parameters. In particular, the speckle orientation and the lateral dependence (x and y) of the longitudinal speckle size can vary significantly. For example, the off-axis longitudinal correlation length remains equal to the on axis size for speckles in a Fourier transform system, while it decreases dramatically as the observation position moves off axis in a Fresnel system. In this paper, we review the speckle correlation function in general linear canonical transform (LCT) systems, clearly demonstrating that speckle properties can be controlled by introducing different optical components, i.e., lenses and sections of free space. Using a series of numerical simulations, we examine how the correlation function changes for some typical LCT systems. The integrating effect of the camera pixel and the impact this has on the measured first- and second-order statistics of the speckle intensities is also examined theoretically. A series of experimental results are then presented to confirm several of these predictions. First, the effect the pixel size has on the measured first-order speckle statistics is demonstrated, and second, the orientation of speckles in a Fourier transform system is measured, showing that the speckles lie parallel to the optical axis. PMID- 22307125 TI - Time-average Fourier telescopy: a scheme for high-resolution imaging through horizontal-path turbulence. AB - The problem of high-resolution imaging through long horizontal-path ground-level turbulence has gone unsolved since it was first addressed many decades ago. In this paper I describe a method that shows promise for diffraction-limited imaging through ground-level turbulence with large (meters) apertures and at large (kilometers) distances. The key lies in collecting image data in the spatial frequency domain via the method of Fourier telescopy and taking suitable time averages of the magnitude and phase of the Fourier telescopy signal. The method requires active illumination of the target with laser light, and the time averages required will likely be over many tens of seconds if not tens of minutes or more. The scheme will thus not be suitable for time-varying scenes. The basic scheme is described, and principle challenges briefly discussed. PMID- 22307126 TI - Applications of the phase transfer function of digital incoherent imaging systems. AB - The phase of the optical transfer function is advocated as an important tool in the characterization of modern incoherent imaging systems. It is shown that knowledge of the phase transfer function (PTF) can benefit a diverse array of applications involving both traditional and computational imaging systems. Areas of potential benefits are discussed, and three applications are presented, demonstrating the utility of the phase of the complex frequency response in practical scenarios. In traditional imaging systems, the PTF is shown via simulation results to be strongly coupled with odd-order aberrations and hence useful in misalignment detection and correction. In computational imaging systems, experimental results confirm that the PTF can be successfully applied to subpixel shift estimation and wavefront coding characterization tasks. PMID- 22307127 TI - High-resolution multiband polarization epithelial tissue imaging method by sparse representation and fusion. AB - Multiband polarization epithelial tissue imaging is an effective tool to measure tissue's birefringence and structure for quantitative pathology analysis. To discriminate the pathology accurately, high-resolution multiband polarization images are essential. But it is difficult to acquire high-resolution polarization images because of the limitations of imaging systems. The polarization image calculation process can be regarded as image fusion with fixed rules, and multiband polarization images are intrinsically sparse. In this paper, we propose a novel high-resolution multiband polarization image calculation method by utilizing the sparse representation and image fusion method. The multiband images are first represented in the sparse domain and we further introduce total variation-regularization terms into the sparse representation framework. Then, polarization parameter images are calculated by simultaneous fusion and reconstruction. Higher quality multiband polarization images can be obtained through additional regularization constraint in the fusion process. Extensive experiments validate that the proposed method achieves much better results than many state-of-the-art algorithms in terms of both peak signal-to-noise-ratio and visual perception. PMID- 22307128 TI - Space-bandwidth scaling for wide field-of-view imaging. AB - We examine the space-bandwidth product of wide field-of-view imaging systems as the systems scale in size. Our analysis is based on one conducted to examine the behavior of a plano-convex lens imaging onto a flat focal geometry. We extend this to consider systems with monocentric lenses and curved focal geometries. As a means to understand system cost, and not just performance, we also assess the volume and mass associated with these systems. Our analysis indicates monocentric lenses imaging onto a curved detector outperform other systems for the same design constraints but do so at a cost in lens weight. PMID- 22307129 TI - Prototype development and field-test results of an adaptive multiresolution PANOPTES imaging architecture. AB - The design, development, and field-test results of a visible-band, folded, multiresolution, adaptive computational imaging system based on the Processing Arrays of Nyquist-limited Observations to Produce a Thin Electro-optic Sensor (PANOPTES) concept is presented. The architectural layout that enables this imager to be adaptive is described, and the control system that ensures reliable field-of-view steering for precision and accuracy in subpixel target registration is explained. A digital superresolution algorithm introduced to obtain high resolution imagery from field tests conducted in both nighttime and daytime imaging conditions is discussed. The digital superresolution capability of this adaptive PANOPTES architecture is demonstrated via results in which resolution enhancement by a factor of 4 over the detector Nyquist limit is achieved. PMID- 22307130 TI - Low-cost multispectral vegetation imaging system for detecting leaking CO2 gas. AB - As a component of a multisensor approach to monitoring carbon sequestration sites for possible leaks of the CO2 gas from underground reservoirs, a low-cost multispectral imaging system has been developed for indirect detection of gas leaks through observations of the resulting stress in overlying vegetation. The imager employs front-end optics designed to provide a full 50 degrees field of view with a small, low-cost CMOS detector, while still maintaining quasi collimated light through the angle-dependent interference filters used to define the spectral bands. Red and near-infrared vegetation reflectances are used to compute the normalized difference vegetation index (NDVI) and spatial and temporal patterns are analyzed statistically to identify regions of anomalous stress, which are then flagged for closer inspection with in-situ CO2 sensors. The system is entirely self-contained with an onboard compact computer and is housed in a weather-proof housing to enable extended outdoor deployment. PMID- 22307131 TI - Space-time compressive imaging. AB - Compressive imaging systems typically exploit the spatial correlation of the scene to facilitate a lower dimensional measurement relative to a conventional imaging system. In natural time-varying scenes there is a high degree of temporal correlation that may also be exploited to further reduce the number of measurements. In this work we analyze space-time compressive imaging using Karhunen-Loeve (KL) projections for the read-noise-limited measurement case. Based on a comprehensive simulation study, we show that a KL-based space-time compressive imager offers higher compression relative to space-only compressive imaging. For a relative noise strength of 10% and reconstruction error of 10%, we find that space-time compressive imaging with 8*8*16 spatiotemporal blocks yields about 292* compression compared to a conventional imager, while space-only compressive imaging provides only 32* compression. Additionally, under high read noise conditions, a space-time compressive imaging system yields lower reconstruction error than a conventional imaging system due to the multiplexing advantage. We also discuss three electro-optic space-time compressive imaging architecture classes, including charge-domain processing by a smart focal plane array (FPA). Space-time compressive imaging using a smart FPA provides an alternative method to capture the nonredundant portions of time-varying scenes. PMID- 22307132 TI - Digital camera simulation. AB - We describe a simulation of the complete image processing pipeline of a digital camera, beginning with a radiometric description of the scene captured by the camera and ending with a radiometric description of the image rendered on a display. We show that there is a good correspondence between measured and simulated sensor performance. Through the use of simulation, we can quantify the effects of individual digital camera components on system performance and image quality. This computational approach can be helpful for both camera design and image quality assessment. PMID- 22307133 TI - Spectrally reconfigurable pixels for dual-color-mode imaging sensors. AB - The use of full color-sensitive photodetectors with three electrically tunable spectral responses allows the design of sensors that can be real-time reconfigured for different color acquisition modes. All the (physically identical) pixels can be biased in the same way, each giving the same set of RGB spectral responses: in this situation the conversion from the sensor color space to a reference color space can be implemented as usual, giving typical color errors DeltaE(a,b) in the order of 2-3. Alternatively, pixels can be biased in two different ways (e.g., row by row), forming pairs: by joining the information from adjacent pixels, the sensor has six spectral responses, with a reduced resolution. By exploiting this plurality of spectral responses, color reproduction accuracy can be increased. In this work, an improved design of the Transverse Field Detector, a filterless and tunable three-color pixel, is used as the experimental device to propose a dual-color-mode reconfigurable sensor. PMID- 22307134 TI - Imaging systems and applications. AB - Imaging systems are used in consumer, medical, and military applications. Designing, developing, and building imaging systems requires a multidisciplinary approach. This issue features current research in imaging systems that ranges from fundamental theories to novel applications. Although the papers collected are diverse, their unique compilation provides a systems perspective to imaging. PMID- 22307135 TI - Atomic layer deposition for nanofabrication and interface engineering. AB - Atomic layer deposition (ALD) provides a tool for conformal coating on high aspect-ratio nanostructures with excellent uniformity. It has become a technique for both template-directed nanofabrications and engineering of surface properties. This Feature Article highlights the application of ALD in selected fields including photonics, SERS and energy materials. Specifically, the topics include fabrication of plasmonic nanostructures for the SERS applications, fabrication of 3-D nanoarchitectured photoanodes for solar energy conversions (dye-sensitized solar cells and photoelectrochemical cells), and coating of electrodes to enhance the cyclic stability and thus device life span of batteries. Dielectric coating for tailoring optical properties of semiconductor nanostructures is also discussed as exemplified by ZnO nanowires. Future direction of ALD in these applications is discussed at the end. PMID- 22307136 TI - L1 cell adhesion molecule promotes tumorigenicity and metastatic potential in non small cell lung cancer. AB - PURPOSE: Non-small cell lung cancer (NSCLC) is a highly metastatic cancer with limited treatment options, thus requiring development of novel targeted therapies. Our group previously identified L1 cell adhesion molecule (L1CAM) expression as a member of a prognostic multigene expression signature for NSCLC patients. However, there is little information on the biologic function of L1CAM in lung cancer cells. This study investigates the functional and prognostic role of L1CAM in NSCLC. EXPERIMENTAL DESIGN: Cox proportional hazards regression analysis was done on four independent published mRNA expression datasets of primary NSCLCs. L1CAM expression was suppressed by short-hairpin RNA (shRNA) mediated silencing in human NSCLC cell lines. Effects were assessed by examining in vitro migration and invasion, in vivo tumorigenicity in mice, and metastatic potential using an orthotopic xenograft rat model of lung cancer. RESULTS: L1CAM is an independent prognostic marker in resected NSCLC patients, with overexpression strongly associated with worse prognosis. L1CAM downregulation significantly decreased cell motility and invasiveness in lung cancer cells and reduced tumor formation and growth in mice. Cells with L1CAM downregulation were deficient in constitutive extracellular signal-regulated kinase (Erk) activation. Orthotopic studies showed that L1CAM suppression in highly metastatic lung cancer cells significantly decreases spread to distant organs, including bone and kidney. CONCLUSION: L1CAM is a novel prometastatic gene in NSCLC, and its downregulation may effectively suppress NSCLC tumor growth and metastasis. Targeted inhibition of L1CAM may be a novel therapy for NSCLC. PMID- 22307137 TI - A phase I study of veliparib in combination with metronomic cyclophosphamide in adults with refractory solid tumors and lymphomas. AB - PURPOSE: Oral administration of the alkylating agent cyclophosphamide at low doses, metronomic dosing, is well tolerated, with efficacy in multiple tumor types. PARP inhibition potentiates effects of cyclophosphamide in preclinical models. We conducted a phase I trial of the PARP inhibitor veliparib and metronomic cyclophosphamide in patients with refractory solid tumors and lymphoid malignancies. EXPERIMENTAL DESIGN: Objectives were to establish the safety and maximum tolerated dose (MTD) of the combination; characterize veliparib pharmacokinetics (PK); measure poly(ADP-ribose) (PAR), a product of PARP, in tumor biopsies and peripheral blood mononuclear cells (PBMC); and measure the DNA damage marker gammaH2AX in PBMCs and circulating tumor cells (CTC). Cyclophosphamide was administered once daily in 21-day cycles in combination with veliparib administered once daily for 7, 14, or 21 days. RESULTS: Thirty-five patients were enrolled. The study treatment was well tolerated, and the MTD was established as veliparib 60 mg with cyclophosphamide 50 mg given once daily. Seven patients had partial responses; an additional six patients had disease stabilization for at least six cycles. PAR was significantly decreased in PBMCs (by at least 50%) and tumor biopsies (by at least 80%) across dose levels (DL); gammaH2AX levels were increased in CTCs from seven of nine patients evaluated after drug administration. CONCLUSIONS: The combination of veliparib with metronomic cyclophosphamide is well tolerated and shows promising activity in a subset of patients with BRCA mutations. A phase II trial of the combination compared with single-agent cyclophosphamide is ongoing in BRCA-positive ovarian cancer, triple-negative breast cancer, and low-grade lymphoma. PMID- 22307138 TI - Sorafenib is an inhibitor of UGT1A1 but is metabolized by UGT1A9: implications of genetic variants on pharmacokinetics and hyperbilirubinemia. AB - PURPOSE: Several case reports suggest sorafenib exposure and sorafenib-induced hyperbilirubinemia may be related to a (TA)(5/6/7) repeat polymorphism in UGT1A1*28 (UGT, uridine glucuronosyl transferase). We hypothesized that sorafenib inhibits UGT1A1 and individuals carrying UGT1A1*28 and/or UGT1A9 variants experience greater sorafenib exposure and greater increase in sorafenib-induced plasma bilirubin concentration. EXPERIMENTAL DESIGN: Inhibition of UGT1A1 mediated bilirubin glucuronidation by sorafenib was assessed in vitro. UGT1A1*28 and UGT1A9*3 genotypes were ascertained with fragment analysis or direct sequencing in 120 cancer patients receiving sorafenib on five different clinical trials. Total bilirubin measurements were collected in prostate cancer patients before receiving sorafenib (n = 41) and 19 to 30 days following treatment and were compared with UGT1A1*28 genotype. RESULTS: Sorafenib exhibited mixed-mode inhibition of UGT1A1-mediated bilirubin glucuronidation (IC(50) = 18 MUmol/L; K(i) = 11.7 MUmol/L) in vitro. Five patients carrying UGT1A1*28/*28 (n = 4) or UGT1A9*3/*3 (n = 1) genotypes had first dose, dose-normalized areas under the sorafenib plasma concentration versus time curve (AUC) that were in the 93rd percentile, whereas three patients carrying UGT1A1*28/*28 had AUCs in the bottom quartile of all genotyped patients. The Drug Metabolizing Enzymes and Transporters genotyping platform was applied to DNA obtained from six patients, which revealed the ABCC2-24C>T genotype cosegregated with sorafenib AUC phenotype. Sorafenib exposure was related to plasma bilirubin increases in patients carrying 1 or 2 copies of UGT1A1*28 alleles (n = 12 and n = 5; R(2) = 0.38 and R(2) = 0.77; P = 0.032 and P = 0.051, respectively). UGT1A1*28 carriers showed two distinct phenotypes that could be explained by ABCC2-24C>T genotype and are more likely to experience plasma bilirubin increases following sorafenib if they had high sorafenib exposure. CONCLUSIONS: This pilot study indicates that genotype status of UGT1A1, UGT1A9, and ABCC2 and serum bilirubin concentration increases reflect abnormally high AUC in patients treated with sorafenib. PMID- 22307139 TI - Detection and characterization of a novel subset of CD8+CD57+ T cells in metastatic melanoma with an incompletely differentiated phenotype. AB - PURPOSE: Tumor-specific T cells are frequently induced naturally in melanoma patients and infiltrate tumors. It is enigmatic why these patients fail to experience tumor regression. Given that CD8(+) T cells mediate antigen-specific killing of tumor cells, the focus of this study was to identify alterations in the differentiation of CD8(+) residing at the tumor site, with emphasis on a population expressing CD57, a marker for terminal differentiation. EXPERIMENTAL DESIGN: We conducted flow cytometric analysis of CD8(+) tumor-infiltrating lymphocytes (TIL) isolated from 44 resected melanoma metastases with known T-cell differentiation markers. For comparison, peripheral blood mononuclear cells were isolated from matched melanoma patients. We sorted different CD8(+) subsets found in TIL and determined their effector functions. In addition, we carried out Vbeta clonotype expression analysis of T-cell receptors to determine lineage relationship between the CD8(+) TIL subsets. RESULTS: The majority of CD8(+) TIL was in the early-effector memory stage of differentiation. A significant population consisted of an oligoclonal subset of cells coexpressing CD27, CD28, CD57, and Granzyme B, with little or no perforin. These cells could be induced to proliferate, produce a high level of IFN-gamma, and differentiate into CD27( )CD57(+), perforin(high) mature CTL in vitro. Addition of TGF-beta1 prevented further differentiation. CONCLUSIONS: Our studies identified a novel subset of incompletely differentiated CD8(+) CTL coexpressing early effector memory and late CTL markers. This population resembles that found in patients with uncontrolled chronic viral infections. TGF-beta1, frequently produced by melanoma tumors, may be a key cytokine inhibiting further maturation of this subset. PMID- 22307140 TI - The fundamental role of the p53 pathway in tumor metabolism and its implication in tumor therapy. AB - It is well established that the altered metabolism exhibited by cancer cells, including high rates of glycolysis, lactate production, and biosynthesis of lipids, nucleotides, and other macromolecules, and which may occur either as a consequence or as a cause of tumorigenesis, plays an essential role in cancer progression. Recently, the tumor suppressor p53 was found to play a central role in this process. Here, we review the role of p53 in modulating tumor metabolism. Specifically, we focus on the functions of p53 in regulating aerobic glycolysis, oxidative phosphorylation, the pentose phosphate pathway, fatty acid synthesis and oxidation, and glutamine metabolism, and we discuss the therapeutic strategy whereby p53 helps to prevent malignant progression. PMID- 22307141 TI - Learned resourcefulness, social support, and perinatal depression in chinese mothers. AB - BACKGROUND: Postnatal depression is a major health problem that can have detrimental effects on infants' psychosocial development; however, there are few longitudinal studies on the protective role of learned resourcefulness against the development of postnatal depression. OBJECTIVES: The aims of this study were to examine the relationships among learned resourcefulness, social support, stress, and depressive symptoms across the perinatal period and to determine the mediating role of learned resourcefulness and social support between stress and depressive symptoms in the perinatal period. METHODS: A longitudinal design was used. A convenience sample of 170 first-time Chinese mothers completed the assessment during pregnancy and were followed up at 6 weeks and 6 months postpartum. The Self-Control Schedule, Medical Outcomes Study Social Support Survey, Social Readjustment Rating Scale, and Edinburgh Postnatal Depression Scale were used. Path analysis was employed. RESULTS: Learned resourcefulness had a direct impact on depressive symptoms and mediated the effect of stress on depressive symptoms during pregnancy and at 6 weeks postpartum. Social support had a direct impact on depressive symptoms and mediated the effect of stress on depressive symptoms during pregnancy. Learned resourcefulness and social support directly predicted depressive symptoms at 6 months postpartum. DISCUSSION: Learned resourcefulness and social support serve to protect against the development of depressive symptoms and mediate the relationship between stress and depressive symptoms in the perinatal period. Culturally competent healthcare should be developed to equip women with learned resourcefulness skills and foster support network to combat the stress of new motherhood, thereby minimizing the risk of perinatal depression. PMID- 22307142 TI - Domestic decision-making power, social support, and postpartum depression symptoms among immigrant and native women in Taiwan. AB - BACKGROUND: Domestic decision-making power is an integral part of women's empowerment. No study has linked domestic decision-making power and social support concurrently to postpartum depression and compared these between immigrant and native populations. OBJECTIVES: The aim of this study was to examine domestic decision-making power and social support and their relationship to postpartum depressive symptoms among immigrant and native women in Taiwan. METHODS: This cross-sectional survey included 190 immigrant and 190 native women who had delivered healthy babies during the past year in Taipei City. Depression was measured using the Edinburgh Postnatal Depression Scale, with a cutoff score of 10. Logistic regression was used to determine the factors associated with postpartum depression symptoms. RESULTS: Immigrant mothers had significantly higher prevalence of postpartum depression symptoms (41.1% vs. 8.4%) and had significantly lower levels of domestic decision-making power and social support than native mothers did. Logistic regression showed that insufficient family income was associated with an increased risk of postpartum depression symptoms, whereas social support and domestic decision-making power levels were associated negatively with postpartum depression symptoms. After accounting for these factors, immigrant women remained at higher risk of postpartum depression symptoms than native women did, odds ratio = 2.59, 95% CI [1.27, 5.28]. DISCUSSION: Domestic decision-making power and social support are independent protective factors for postpartum depression symptoms among immigrant and native women in Taiwan. Social support and empowerment interventions should be tested to discover whether they are able to prevent or alleviate postpartum depression symptoms, with special emphasis on immigrant mothers. PMID- 22307143 TI - The coping experience of Taiwanese male donors in living donor liver transplantation. AB - BACKGROUND: Living donor liver transplantation is an option for effective treatment for patients with liver disease or a liver tumor. One disadvantage, however, is the risk of complications or death in a healthy donor. Thus, promoting the donor's safety and well-being is a major goal of transplantation care. In this regard, more research on physical and psychological complications and adjustment among donors is needed. OBJECTIVES: The aim of this study was to describe the experiences of living liver donors, focusing on their perceptions of living liver transplantation and corresponding coping strategies. METHODS: The data were analyzed using content analysis in this qualitative design. RESULTS: Seven of 12 donors, all men, agreed to participate in the study. The core theme that emerged in regard to adjustment was "maintaining peace of mind." In addition, there were 4 subthemes: (a) removing themselves from information, (b) viewing the surgery as common, (c) having overall confidence, and (d) assigning value to their decision. DISCUSSION: Living donor liver transplantation is a treatment option that requires acceptance by both the donor and his or her family. The process is enormously stressful, and the living liver donor needs adjustment strategies to maintain his or her peace of mind throughout the process. PMID- 22307144 TI - Efficacy of a health-promotion intervention for college students: a randomized controlled trial. AB - BACKGROUND: Diabetes is a leading cause of death in Mexico. Research has shown that encouraging healthy behaviors, especially among younger people, is an effective way to reduce chronic illnesses such as diabetes and the related morbidity and mortality from these diseases. OBJECTIVES: The aim of this study was to test the efficacy of a brief health-promotion intervention in encouraging a health-promoting lifestyle in university students. METHODS: A 2-group randomized controlled experimental design was used. Seventy-three freshman Mexican students (31 in the experimental group and 42 in the control group) participated in the study. The experimental group attended a7-session program, with a duration of 2 hours per session. Lifestyle was measured using the Health Promoting Lifestyle Profile-II questionnaire. Repeated-measures and factorial analysis of variance were computed. RESULTS: There was a significant main effect of the intervention in all dependent health profile variables, F(2, 138) = 3.46 14.45, p < .03. In addition, we found a significant interaction between group and time for the overall health profile score, F(2, 138) = 8.73, p < .0001, physical activity, F(2, 138) = 4.68, p = .01, nutrition, F(2, 138) = 3.57, p = .03, health responsibility, F(2, 138) = 5.31, p = .006, and stress management, F(2, 138) = 8.71, p < .0001. DISCUSSION: This interaction indicated that lifestyle differed in the intervention and control groups across the measurements at different times. Students attending the intervention presented a healthier lifestyle than did students in the control group. These results offer interesting experimental evidence to establish guidelines for the design of healthier universities. PMID- 22307145 TI - Alterations in progesterone receptor membrane component 2 (PGRMC2) in the endometrium of macaques afflicted with advanced endometriosis. AB - The hormonally driven expression and cell-specific localization patterns of the progesterone receptor membrane components (PGRMC1 and PGRMC2) in the macaque endometrium during the menstrual cycle are unknown. Additionally, the expression and localization patterns of PGRMC1 and PGRMC2 in the secretory eutopic endometrium of primates afflicted with endometriosis are also unknown. Therefore, we used real-time PCR to quantify transcript expression levels of the PGRMCs in well-defined samples of endometrium collected from artificially cycled macaques during the menstrual cycle, and in the secretory phase endometrium of naturally cycling macaques afflicted with endometriosis. In situ hybridization and immunocytochemistry were used to localize PGRMC1 and PGRMC2 mRNA and protein, respectively. We compared the patterns of expression and localization of the PGRMCs with the expression and localization patterns of nuclear progesterone receptor (PGR). PGRMC1 and PGR were elevated during the proliferative phases of the cycle, and then declined to nearly undetectable levels during the late secretory phase of the cycle. Levels of PGRMC2 were lowest during the proliferative phases of the cycle and then increased markedly during the secretory phases. Strong staining for PGRMC2 was localized to the luminal and glandular epithelia during the secretory phases. When compared with artificially cycled disease-free animals, macaques with endometriosis exhibited no changes in the expression or localization patterns for PGR and PGRMC1 but exhibited strikingly reduced levels of PGRMC2 transcript and altered intracellular staining patterns for the PGRMC2 protein. Collectively, these results suggest that membrane-bound PGRMC2 may provide a pathway of action that could potentially mediate the non-genomic effects of progesterone on the glandular epithelia during the secretory phase of the cycle. Further, reduced levels of membrane-bound PGRMC2 may be associated with the progesterone insensitivity often observed in the endometrium of primates afflicted with endometriosis. PMID- 22307146 TI - 2nd Hypertension Research Award for authors of outstanding papers in HR. PMID- 22307148 TI - Effect of a hot water extract of Chlorella vulgaris on proliferation of IEC-6 cells. AB - Chlorella vulgaris, a unicellular microalgae, exerts various biological effects; however their effect on proliferation signaling pathways in normal cells has not been studied. We investigated the effect of hot water extracts of Chlorella vulgaris (CVE) on cell proliferation and related signaling pathways in rat intestinal epithelial cells (IEC-6). CVE increased the expression of insulin-like growth factor-I receptor (IGF-IR) and the phosphorylation of focal adhesion kinase (FAK) and Src. In addition, CVE induced activation of the mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways. We verified the increased phosphorylation of extracellular-signal related kinase (ERK) and Akt and the increased expression of the PI3K regulatory subunit p85. CVE also influenced the canonical Wnt pathway through increased expression of the nuclear beta-catenin, cyclin D1. Tyr-397 of FAK mediates interactions with Src homology 2 (SH2) domains in a number of other signaling proteins, including PI3K, PLC-gamma, Shc, Grb7, Src and Nck2. Because CVE induced FAK activation, FAK may affect the Wnt pathway. Addition of a FAK inhibitor decreased the expression of nuclear beta-catenin, cyclin D1 and c-myc, and increased the expression of cytosolic beta-catenin. We conclude that CVE stimulated proliferation of IEC-6 cells via the MAPK, PI3K/Akt and canonical Wnt pathways, and that this affected the canonical Wnt pathway. PMID- 22307149 TI - Ionic liquid based hollow fiber supported liquid phase microextraction of ultraviolet filters. AB - Hollow fiber protected liquid phase microextraction using an ionic liquid as supported phase and acceptor phase (IL-HF-LPME) is proposed for the determination of four ultraviolet (UV) filters (benzophenone, 3-(4-methylbenzylidene)-camphor, 2-hydroxy-4-methoxybenzophenone and 2,4-dihydroxybenzophenone) in water samples for the first time. In the present study, four different ILs 1-hexyl-3 methylimidazolium tris(pentafluoroethyl)trifluorophosphate) [HMIM][FAP], 1-butyl 1-methylpyrrolidinium tris(pentafluoroethyl)trifluorophosphate [BMPL][FAP], 1 butyl-3-methylimidazolium phosphate ([BMIM][PO(4)]) and 1-butyl-3 methylimidazolium hexafluorophosphate ([BMIM][PF(6)]) were evaluated as extraction solvent. Only [HMIM][FAP] showed high chemical affinity to the analytes which permits a selective isolation of the UV filters from the sample matrix, allowing also their preconcentration. IL-HF-LPME and high performance liquid chromatography provides repeatability from 1.1% to 8.2% and limits of detection between 0.3 and 0.5 ng/ml. Real water samples spiked with the analytes extracted were analyzed, and yielded relative recoveries ranging from 82.6% to 105.9%. PMID- 22307150 TI - Overcoming the high-temperature two-dimensional gas chromatography limits to elute heavy compounds. AB - Overcoming high-temperature (HT) two-dimensional gas chromatography (GC * GC) limits is critical for the analysis of heavy hydrocarbons, particularly those contained in heavy petroleum fractions. To reach this goal, HT-GC * GC analysis was adapted from HT-GC Simulated Distillation (HT-GC SimDist) operating conditions as this analysis embraces compounds whose boiling point ranges from 35 degrees C to 700 degrees C and from a previous study that enabled the elution of linear alkane nC(60) and tetraaromatic compounds by HT-GC * GC. This paper shows that HT-GC * GC analysis using CO(2) cryogenic modulator and short wide bore columns with a thin film of stationary phase allows the elution of linear alkanes up to nC(68) (641 degrees C) as well as of highly aromatic hydrocarbons like coronene. Furthermore, compared to previous studies, an on-column injector was used to reduce discrimination of high boiling point compounds. PMID- 22307151 TI - Design, synthesis and evaluation of a molecularly imprinted polymer for hollow fiber-solid phase microextraction of chlorogenic acid in medicinal plants. AB - In this study, a simple preparation approach was developed for modified bisphenol A (BPA) molecularly imprinted polymer sorbent used in the hollow fiber solid phase microextraction (MIP-HF-SPME) of chlorogenic acid (CGA). The pre-polymer solution containing the template was introduced into the polypropylene hollow fiber segment for in situ polymerization. MIP-HF-SPME conditions based on the modified MIP-sorbent were optimized. Finally, the tool was used for selective extraction of chlorogenic acid in Echinacea purpurea, a medicinal plant. Main parameters affecting synthesis of organic-inorganic hybrid MIP and microextraction procedure were investigated and optimized. The measurements were done under the optimal conditions. The limit of detection has been gained 0.08 ng/mL. The linear range and relative standard deviation (RSD %) are 0.2-1000 ng/mL and 0.38 (n=3) respectively. The average relative recoveries of spiked analyte in the four concentration levels were between 84.8 and 97.2%. PMID- 22307152 TI - Approaches to find complementary separation conditions for resolving complex mixtures by high-performance liquid chromatography. AB - Chromatographic problems are usually addressed trying to find out a single experimental condition aimed to resolve all compounds in the sample. However, very often, the chromatographic system is not able to provide full resolution. When a separation fails, the usual choice is introducing a drastic change in the chromatographic system (e.g. column, solvent, pH). There are, however, other possibilities that take advantage of the gathered information in the failed separation, without the need of new experiments, based on the concept of complementary separations (e.g. isocratic mobile phases, gradients, columns, chromatographic modes). One separation condition will focus on the resolution of some compounds in the sample, while the other compounds will be resolved using a second (or subsequent) condition(s). Complementary separations, being a simple and attractive idea, present, however, challenges in terms of computation volume and complexity of the required algorithms. This work describes in detail different approaches that have been developed up-to-date for this purpose, and introduces a new approach based on the peak count concept that is benefited of the best features of the previous approaches: high reliability in finding the solution, accessibility to analysts without specialised programming skills and short computation time. PMID- 22307153 TI - Ionic liquid based in situ solvent formation microextraction coupled to thermal desorption for chlorophenols determination in waters by gas chromatography/mass spectrometry. AB - A simple and efficient method for the determination of ten chlorophenols (including mono, di, tri, tetra and pentachlorophenols) in water samples is presented. The analytical method is based on a previous derivatization of the target compounds with acetic anhydride, being the derivatized compounds finally isolated/preconcentrated by an in situ solvent formation microextraction. Later on the extractant (an ionic liquid) containing the analytes is recovered by centrifugation and thermally desorbed. The analytes are finally separated and determined by gas chromatography/mass spectrometry. The main variables involved in the extraction and thermal desorption steps have been studied in depth. Once evaluated, the analytical method has been characterized in terms of linearity, sensitivity, precision and accuracy. The limits of detection were in the range from 60 ng L(-1) (4-chlorophenol) to 440 ng L(-1) (pentachlorophenol) while the precision, expressed as relative standard deviation, was in the interval from 4.5% (2,6-dichlorophenol) to 9.9% (3-chlorophenol). In addition, acceptable recovery values were obtained in samples of different nature, including river, tap and reservoir water samples. PMID- 22307154 TI - Separation of a binary mixture by sequential centrifugal partition chromatography. AB - Sequential centrifugal partition chromatography (sCPC) is a novel continuous cyclic liquid-liquid chromatographic separation technology. Each cycle of the process comprises two steps, which differ by the liquid phase used as mobile phase (upper or lower phase) and its flow direction. The feed is introduced continuously in the unit and two product streams are collected alternately, in each step of the cycle. In this work, the sCPC was modeled using the stage (cell) model. The model was used to simulate a separation of a model binary mixture consisting of pyrocatechol and hydroquinone. The solutes distribution constants, system hydrodynamics and mass transfer parameters were determined experimentally and implemented in the model. Furthermore, a parameter study (variation of the feed concentration and step times) was performed by experiments and simulation. A recently developed method was used to select the operating parameters of the sCPC unit. PMID- 22307155 TI - Gradient HPLC of samples extracted from the green microalga Botryococcus braunii using highly efficient columns packed with 2.6 MUm Kinetex-C18 core-shell particles. AB - The analysis of the nonpolar extract of the cells of colonies of the green colonial microalgae Botryococcus braunii was performed by gradient HPLC. The growth of B. braunii was stressed by reducing its nitrogen nutrients by 90%, in order to enhance the production of nonpolar compounds. Highly efficient 4.6mm * 100mm columns packed with 2.6 MUm Kinetex-C(18) core-shell particles (Phenomenex, Torrance, CA, USA) were used. The gradient mobile phase was a mixture of acetonitrile and water (70-97%, v/v). Its initial and final compositions during the gradient elution were chosen so that the retention factors of the last eluted compound at the inlet and outlet of the column were 15 and 1, respectively. The highest peak capacity was obtained by optimizing several experimental parameters, including the injected sample volume, the flow rate, and the column length. The highest resolution was obtained by connecting one 4.6 mm * 150 mm and three 4.6mm * 100mm columns (total length 45 cm). The optimum flow rate was 1.5 mL/min, which provided the minimum plate height for the most retained compounds, the optimum inlet pressure was 930 bar and the injected volume 2 MUL. The analysis time was then 14 min for a peak capacity of 121. The trends observed for the variation of the experimental peak capacity with the flow rate and the column length are in excellent agreement with theoretical predictions. PMID- 22307170 TI - Dominance of resistance-breaking cotton leaf curl Burewala virus (CLCuBuV) in northwestern India. AB - Cotton leaf curl disease (CLCuD) is a major limitation to cotton production on the Indian subcontinent. A survey for viruses causing CLCuD was conducted during the 2009 and 2010 cropping seasons in the northwestern Indian cotton-growing belt in the states of Punjab, Haryana and Rajasthan. Partial sequences of 258 and full length sequences of 22 virus genomes were determined. This study shows that the resistance-breaking cotton leaf curl Burewala virus (CLCuBuV) is now the dominant virus in many fields. The spread and establishment of the mutant CLCuBuV in northwestern India, the variation in its genomic sequence, its virulence and infectivity, and the implications for cotton breeding are discussed. PMID- 22307171 TI - Synthesis and photoluminescence properties of Ce3+ and Eu2+-activated Ca7Mg(SiO4)4 phosphors for solid state lighting. AB - Ce(3+) and Eu(2+) singly doped and Ce(3+)/Eu(2+)-codoped Ca(7)Mg(SiO(4))(4) phosphors are synthesized by the conventional solid state reaction. The Ce(3+) activated sample exhibits intense blue emission under 350 nm excitation, the composition-optimized Ca(7)Mg(SiO(4))(4) : 4%Ce(3+) shows better color purity than the commercial blue phosphor, BaMgAl(10)O(17) : Eu(2+) (BAM : Eu(2+)) and exhibits superior external quantum efficiency (65%). The Ca(7)Mg(SiO(4))(4) : Eu(2+) powder shows a broad emission band in the wavelength range of 400-600 nm with a maximum at about 500 nm. The strong excitation bands of the Ca(7)Mg(SiO(4))(4) : Eu(2+) in the wavelength range of 250-450 nm are favorable properties for applications as light-emitting-diode conversion phosphors. Furthermore, the energy transfer from the Ce(3+) to Eu(2+) ions is observed in the codoped samples, the resonance-type energy transfer is determined to be due to the dipole-dipole interaction mechanism and the critical distance is obtained through the spectral overlap approach and concentration quenching method. PMID- 22307172 TI - Mitochondrial localization of P-glycoprotein in the human breast cancer cell line MCF-7/ADM and its functional characterization. AB - The current view of multidrug resisitance is that overexpression of membrane P glycoprotein (P-gp) is a major causative factor. However, the controversial presence of subcellular P-gp may also participate in the drug resistance. In this study, we sought to investigate the localization and functional characterization of P-gp in mitochondria isolated from MCF-7 and doxorubicin-resistant MCF-7 (MCF 7/ADM) cells. Mitochondria were isolated and purified from the MCF-7 cell line and its resistant cells MCF-7/ADM. We used electron microscopy, western blot analysis and confocal microscopy to demonstrate the localization of P-gp in the mitochondria of MCF-7/ADM cells. Flow cytometry was used to evaluated the efflux function of mitochondrial P-gp in the presence or absence of the P-gp inhibitor cyclosporine A (CsA). Mitochondria were isolated and purified successfully and were analyzed by electron microscopy. Western blotting demonstrated the expression of P-gp in the cell membrane and purified mitochondria from MCF-7/ADM cells but not from sensitive MCF-7 cells. Immunofluorescence analysis using confocal microscopy demonstrated the localization of P-gp [labeled with green fluorescence (FITC)] to the mitochondria [labeled with red fluorescence (Mitotracker Deep red 633)] of MCF-7/ADM cells and that was absent in MCF-7 cells. Rho123 (a mitochondrial fluorescent probe) accumulation was largely reduced and efflux was strongly increased in the mitochondria of MCF-7/ADM cells compared to those of MCF-7 cells (P<0.01), and these were completely reversed in the presence of the P-gp inhibitor CsA (P<0.01). No significant changes were observed in the mitochondria of MCF-7 cells (P>0.05). P-gp is expressed in the mitochondria of doxorubicin-resistant MCF-7 cells and has an efflux function. It could be involved in multidrug resistance at the subcellular site by pumping out anticancer drugs from mitochondria to protect the function of mitochondria. PMID- 22307173 TI - Recovery of H14 influenza A virus isolates from sea ducks in the Western Hemisphere. AB - In 2010, H14 influenza A viruses were recovered from clinically normal sea ducks in the United States. These are the first H14 isolates recovered in the Western Hemisphere and represent the only documented H14 influenza A viruses isolated since the original isolates were recovered from near the Caspian Sea during 1982. PMID- 22307174 TI - Preparation of aminomethyl functionalised silanes via an alpha-lithiated amine: from their synthesis, stability and crystal structures to stereochemical issues. AB - The preparation of aminomethyl functionalised silanes based on the alpha lithiated amine, (1R,2R)-N,N,N',N'-tetramethylcyclohexane-1,2-diamine [(R,R) TMCDA] is reported. This methodology can be applied for the synthesis of mono aminomethyl substituted systems, but most remarkably also for di- and trifunctionalised compounds. The trapping of the lithiated amine is accompanied by transmetallation reactions resulting in the formation of (silylmethyl)silanes depending on the reaction temperature. The zinc(II) halide complexes of the mono functionalised systems show the formation of exclusively one configuration of the stereogenic nitrogen atom, in which the spatially more demanding substituent exhibits the pseudo-equatorial position. The di- and trifunctionalised systems feature high sensitivity towards Si-C bond cleavage under re-formation of the (R,R)-TMCDA fragment. PMID- 22307175 TI - Controlled synthesis of nanocrystalline Li2MnSiO4 particles for high capacity cathode application in lithium-ion batteries. AB - Monodispersed Li(2)MnSiO(4) nanoparticles are synthesized via a supercritical solvothermal method at 300 degrees C for 5 min reaction time. The as-synthesized nanoparticles are free from impurities and have 15-20 nm diameter. After coating with conductive polymer, a discharge capacity of 313 mA h g(-1) is obtained for the first time because of nearly 2Li(+) reaction. PMID- 22307176 TI - Dysregulation of global microRNA expression in splenic marginal zone lymphoma and influence of chronic hepatitis C virus infection. AB - The precise molecular pathogenesis of splenic marginal zone lymphoma (SMZL) is still unknown. Clinical and epidemiological data suggest that chronic hepatitis C virus (HCV) infection may have an etiological role in a subset of cases.We performed a large-scale microRNA (miRNA) expression profiling analysis of 381 miRNAs by quantitative reverse transcription PCR (Q-RT-PCR) of 26 microdissected splenic tissue samples (7 HCV(+) SMZL; 8 HCV(-) SMZL and 11 non-neoplastic splenic controls). Single assay Q-RT-PCR and miRNA in situ hybridization (miRNA ISH) were used to confirm the results in an independent cohort. Unsupervised hierarchical clustering of miRNA expression profiles demonstrated a distinct signature of SMZL compared with the normal splenic marginal zone. Supervised analysis revealed differentially expressed miRNAs, including miRNAs with previously recognized tumor suppressive or oncogenic potential. Five miRNAs were found significantly overexpressed in SMZL, including miR-21, miR-155 and miR 146a, whereas seven miRNAs showed significantly reduced expression, including miR 139, miR-345, miR-125a and miR-126. Furthermore, we identified miR-26b, a miRNA known to have tumor suppressive properties, as significantly downregulated in SMZL arising in HCV-positive patients (P=0.0016). In conclusion, there is a characteristic dysregulation of miRNA expression in SMZL with a possible implication in its molecular tumorigenesis. PMID- 22307177 TI - Unraveling the role of FANCD2 in chronic myeloid leukemia. PMID- 22307178 TI - Standardization of flow cytometry in myelodysplastic syndromes: a report from an international consortium and the European LeukemiaNet Working Group. AB - Flow cytometry (FC) is increasingly recognized as an important tool in the diagnosis and prognosis of myelodysplastic syndromes (MDS). However, validation of current assays and agreement upon the techniques are prerequisites for its widespread acceptance and application in clinical practice. Therefore, a working group was initiated (Amsterdam, 2008) to discuss and propose standards for FC in MDS. In 2009 and 2010, representatives from 23, mainly European, institutes participated in the second and third European LeukemiaNet (ELN) MDS workshops. In the present report, minimal requirements to analyze dysplasia are refined. The proposed core markers should enable a categorization of FC results in cytopenic patients as 'normal', 'suggestive of', or 'diagnostic of' MDS. An FC report should include a description of validated FC abnormalities such as aberrant marker expression on myeloid progenitors and, furthermore, dysgranulopoiesis and/or dysmonocytopoiesis, if at least two abnormalities are evidenced. The working group is dedicated to initiate further studies to establish robust diagnostic and prognostic FC panels in MDS. An ultimate goal is to refine and improve diagnosis and prognostic scoring systems. Finally, the working group stresses that FC should be part of an integrated diagnosis rather than a separate technique. PMID- 22307179 TI - Comparison of classical chromatographic tests with a chromatographic test applied to stationary phases prepared by thermal immobilization of poly(methyloctylsiloxane) onto silica. AB - Stationary-phase evaluation in reversed-phase liquid chromatography (RP-LC) is not a straightforward process. A number of tests to characterize and classify stationary phases have been suggested. The results of these various tests, however, do not always describe the real properties of the stationary phase. This study critically compares several tests for RP-LC stationary phases, including the Engelhardt, Tanaka, and SRM 870 tests, as well as an in-house test, with emphasis on the stationary-phase descriptors of hydrophobicity and silanol activity. The stationary phases were prepared by thermal immobilization of poly(methyloctylsiloxane) onto silica. Hydrophobicity data from the tests were generally good and interchangeable between the several tests. In contrast, the silanol activity results of the various tests differ significantly. As a consequence, stationary phase classification with respect to silanol activity depends considerably on the test method applied. A new classification method for silanol activity is proposed. PMID- 22307180 TI - Bioaccessibility of total arsenic and arsenic species in seafood as determined by a continuous online leaching method. AB - A continuous leaching method coupled online with inductively coupled plasma mass spectrometry (ICP-MS) detection was used to assess the maximum bioaccessibility of arsenic (As) in seafood samples. The method simulates continuous-flow digestion by successively pumping artificial saliva, gastric and intestinal juices through a mini-column of powdered sample directly connected to the nebuliser of an ICP-MS instrument. The method allows the real-time measurement of As being released by a given reagent. Because the analyte is continuously removed from the system, in contrast to batch methods, the dissolution equilibrium is driven to the right, hence quickly providing information about the worst-case scenario. Following consecutive leaching by the digestive reagents, the leachates were subject to speciation analysis by ion-exchange chromatography with ICP-MS detection to determine the arsenic species released. Finally, the remaining residue from the mini-column was fully digested to verify mass balance. The method was used to determine the bioaccessibility of total As and As species in four certified reference materials and in several real seafood samples. The mass balance was verified in each case. Generally speaking, the non-toxic form was easily released whereas the inorganic forms were poorly bioaccessible. PMID- 22307182 TI - Posterior reversible encephalopathy syndrome in childhood: report of four cases and review of the literature. AB - BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a recently described disorder with typical radiological findings of bilateral gray and white matter abnormalities in the posterior regions of the cerebral hemispheres and cerebellum. Its clinical symptoms include headache, decreased alertness, mental abnormalities such as confusion, diminished spontaneity of speech, and changed behavior ranging from drowsiness to stupor, seizures, vomiting, and abnormalities of visual perception such as cortical blindness. In this study, the clinical and radiological findings of 4 children with this syndrome due to a variety of conditions are reported. METHODS: The records of 4 children with a diagnosis of PRES were retrospectively analyzed. RESULTS: PRES is associated with a disorder of cerebrovascular autoregulation of multiple etiologies. Four patients with PRES who had primary diagnoses of severe aplastic anemia, nephritic syndrome, Henoch Schonlein purpura, and acute poststreptococcal glomerulonephritis are presented. This syndrome has been described in numerous medical conditions, including hypertensive encephalopathy, eclampsia, and with the use of immunosuppressive drugs. CONCLUSIONS: Early recognition of PRES as a complication during different diseases and therapies in childhood may facilitate precise diagnosis and appropriate treatment. PMID- 22307183 TI - Loud clicking sounds associated with rapid soft palate muscle contractions. AB - An 8-year-old boy was seen by his primary care pediatrician with a chief complaint of "intermittent rapid vibrations of the epiglottis" that began several weeks prior. Intraoral examination revealed rapid, symmetrical bilateral contractions of the soft palate muscles (velum), accompanied by clicking sounds audible to physician (objective tinnitus) and patient. The patient was able to volitionally control the initiation and cessation of the palatal movements. The child's mother stated that there had been no clicking noises heard while the boy was sound asleep. Palatal "clonus" was tentatively diagnosed as the cause of the problem. A normal magnetic resonance imaging study with contrast enhancement confirmed that there was no anatomical basis for the localized movement disorder.Palatal myoclonus is an uncommon localized intraoral movement disorder. There are 2 distinct types, and our patient was diagnosed with the essential palatal myoclonus type. This type is characteristically associated with clicking tinnitus, heard by the affected person as well as those in close proximity. The clicking noise is not continuous, ceases during sleep, and is not lifelong. PMID- 22307184 TI - Interpeduncular fossa lipoma: a novel cause of oculomotor nerve palsy in childhood. AB - Oculomotor nerve palsy is a rare finding in children and, when reported, is most frequently either congenital or acquired from postnatal trauma, infection, aneurysm, or migraine. Intracranial lipomas also represent an uncommon finding in children, and although their development is not completely understood, they are now thought to be congenital in nature. Here, we describe the case of a 23-month old boy presenting to the emergency department with left-sided, complete, pupil involving oculomotor nerve palsy. On magnetic resonance imaging, he was found to have an intracranial lipoma of the left interpeduncular fossa. The patient had gradual and spontaneous improvement of symptoms, with complete resolution reported at the 4-month follow-up visit. However, a second magnetic resonance image at 6 months revealed that the lipoma did not change in size. To our knowledge, intracranial lipomas have been previously reported as a possible cause of partial oculomotor nerve palsy in only one adult and have never been reported in a child. In addition, we did not find any reports of intracranial lipomas as a cause of complete, pupil-involving oculomotor palsy, although they are known to cause other cranial nerve pathology. We conclude that intracranial lipomas, although rare, should be considered in the differential diagnosis for oculomotor nerve palsy in children. Further investigation is needed to determine the true incidence of this association. PMID- 22307185 TI - Heart failure secondary to dilated cardiomyopathy: a role for emergency physician bedside ultrasonography. AB - Heart failure as a result of cardiomyopathy is an uncommon presentation in the pediatric emergency department (PED). The initial presenting symptoms in these cases are often nonspecific and may be confused with more common pediatric illnesses. We report a case of a 3-year-old girl initially discharged from a PED after routine evaluation of vomiting and diarrhea with a diagnosis of acute gastroenteritis only to return 1 week later in heart failure from a dilated cardiomyopathy. A bedside ultrasound performed by the emergency physician in the PED allowed for the initiation of appropriate, rapid, goal-directed therapy and expedited timely transport to a facility with pediatric cardiothoracic surgery. We will review dilated cardiomyopathy and the role of emergency physician echocardiography. PMID- 22307186 TI - Non-operative treated spontaneous spinal epidural hematoma in a 12-year-old boy. AB - Spontaneous spinal epidural hematoma (SSEH) has been reported as a rare condition especially in childhood. Because its symptoms are atypical, it is not easy to diagnose the onset of SSEH. However, with wider use of magnetic resonance imaging (MRI), several SSEH cases, especially not requiring surgical intervention, have been reported. We report on a 12-year-old boy who presented with a 5-day history of progressive pain in his back and extremities and numbness of his lower legs. An MRI of the spine demonstrated a dorsal epidural hematoma extending from C4 to T4, and the axial scan of the MRI revealed a posterior hematoma. Neurological deficit was estimated as not severe and not progressive, therefore surgery was postponed, and the patient was discharged without surgical intervention. Seven months later, MRI and myelography were performed, and we confirmed that the spinal epidural hematoma was absorbed. There have been some cases showing spontaneous regression of SSEH, and in younger than 18 years old, most of those cases that were treated with hematopathy such as hemophilia and spontaneous regression after SSEH correlated to larger size of hematoma. Because of bleeding tendencies in these cases the spinal cord was not pressed by the hematoma; this contributed conclusively to the prognosis. On the contrary, the 12-year-old boy, not having bleeding tendency, had the larger lesion of SSEH and recovered spontaneously without surgical intervention. Evaluation of MRI findings and neurological deficits in SSEH cases is important for deciding the indication of surgical intervention. PMID- 22307187 TI - Thrombolytic therapy for acute stroke in a teenager. AB - BACKGROUND: The importance of thrombolytic therapy within the first 3 hours of onset of symptoms of an acute stroke has been stressed, and in consequence, the diagnosis is most commonly made based on clinical grounds. Intracranial hemorrhage is the major life-threatening complication with the use of thrombolytic therapy. Because of the very small time window before administering thrombolytics, it is often not possible to investigate the unusual causes of a stroke that occurs most often in children. OBJECTIVE: This study aimed to present the decision and risk of thrombolysis for an acute ischemic stroke in children. CASE: A case of a teenager with an acute ischemic stroke who received thrombolysis and had resolution of symptoms. CONCLUSIONS: Thrombolytic therapy is effective in acute ischemic strokes; however, in children, one must consider and exclude stroke mimickers and recognize that potentially life-threatening bleeding complicates the use of these medications. PMID- 22307188 TI - Anorexia nervosa: a case report of a teenager presenting with bradycardia, general fatigue, and weakness. AB - BACKGROUND: Anorexia nervosa is a disease with high prevalence in adolescents and carries the highest mortality of any psychiatric disorder. CASE: We present a case of a 17-year-old female presenting to the emergency department with bradycardia that was subsequently diagnosed with anorexia nervosa. We also review the clinical features, diagnosis, complications, and emergency department management of this disease. CONCLUSIONS: Patients with anorexia may present with multiple medical complaints, and it is imperative that the emergency physician be familiar with the syndrome so as to correctly identify and treat patients with this disease. PMID- 22307189 TI - Posttraumatic pulmonary pseudocysts as a manifestation of child abuse. AB - Posttraumatic pulmonary pseudocysts (PTPPCs) are air-, fluid-, or blood-filled spaces in the lung parenchyma. They are rare findings and are associated with substantial blunt force trauma to the chest. Cases in the literature have primarily reported PTPPCs as a result of motor vehicle accidents. There has not been a case of PTPPC reported in the child abuse literature. This case report describes a child with a PTPPC secondary to inflicted abusive injury. PMID- 22307190 TI - Late presentation of massive pleural effusion from intrathoracic migration of a ventriculoperitoneal shunt catheter: case report and review of the literature. AB - We report an unusual case of ventriculoperitoneal (VP) shunt intrathoracic migration, associated with massive symptomatic hydrothorax. The VP shunt was inserted 10 years before presentation, after hemorrhagic hydrocephalus caused by prenatal intraventricular hemorrhage. The pleural fluid was drained via tube thoracostomy and the shunt was externalized, with full resolution of symptoms and signs. The patient was subsequently managed with shunt revision with drainage into the abdominal cavity. We review the 10 pediatric cases of cerebrospinal fluid hydrothorax reported in the literature and discuss the mechanism of shunt tip migration. Pleural effusion secondary to VP shunt insertion is a rare and potentially life-threatening occurrence, and it should be suspected in any patient with a VP shunt and respiratory distress. PMID- 22307191 TI - Ultrasound-guided femoral nerve block for pain control in an infant with a femur fracture due to nonaccidental trauma. AB - A 3-month-old infant girl was transferred to our emergency department (ED) with a subtrochanteric femoral neck fracture due to nonaccidental trauma. She received multiple doses of parenteral analgesics both before arrival and in our ED. We performed an ultrasound-guided femoral nerve block using 2.0 mL of 0.25% bupivicaine (approximately 1.25 mg/kg) before placing the patient in a Pavlik harness. Successful pain control was achieved within 15 minutes of the procedure allowing pain-free manipulation of the affected extremity. The patient required only a single dose of parenteral narcotics during the ensuing 18 hours. To our knowledge, this is the first report of an ultrasound-guided femoral nerve block used in the ED for pain control in a pediatric patient. PMID- 22307192 TI - Intraosseous vascular access for in-hospital emergency use: a systematic clinical review of the literature and analysis. AB - Intraosseous (IO) vascular access is a viable primary alternative in patients requiring emergent vascular access in the hospital emergency department (ED) (eg, resuscitation, shock/septic shock) but is underutilized. OBJECTIVES: This review has 3 objectives: (1) review the evidence supporting the use of IO access; (2) determine the utilization of IO access as described in the literature; and (3) assess the level of specialty society support. METHODS: Electronic and hand searches were undertaken to identify relevant articles. English-language-only articles were identified. The Cochrane Review methodology along with data forms were used to collect and review data. The evidence evaluation process of the international consensus on emergency cardiovascular care was used to assess the evidence. Studies were combined where meta-analyses could be performed. RESULTS: In levels 2 to 5 studies, IO access performed better versus alternative access methods on the end points of time to access and successful access. Complications appeared to be comparable to other venous access methods. Randomized controlled trials are lacking. Newer IO access technologies appear to do a better job of gaining successful access more quickly. Intraosseous access is underutilized in the ED because of lack of awareness, lack of guidelines/indications, proper training, and a lack of proper equipment. CONCLUSIONS: Recommendations/guidelines from physician specialty societies involved in the ED setting are also lacking. Underutilization exists despite recommendations for IO access use from a number of important medical associations peripherally involved in the ED such as the American Academy of Pediatrics. To encourage the IO approach, IO product champions (as both supporter and user) in the ED are needed for prioritizing and assigning IO access use when warranted. In addition, specialty societies directly involved in emergent hospital care should develop clinical guidelines for IO use. PMID- 22307193 TI - Emergency management of increased intracranial pressure. AB - Primary neurological injury in children can be induced by diverse intrinsic and extrinsic factors including brain trauma, tumors, and intracranial infections. Regardless of etiology, increased intracranial pressure (ICP) as a result of the primary injury or delays in treatment may lead to secondary (preventable) brain injury. Therefore, early diagnosis and aggressive treatment of increased ICP is vital in preventing or limiting secondary brain injury in children with a neurological insult. Present management strategies to improve survival and neurological outcome focus on reducing ICP while optimizing cerebral perfusion and meeting cerebral metabolic demands. Targeted therapies for increased ICP must be considered and implemented as early as possible during and after the initial stabilization of the child. Thus, the emergency physician has a critical role to play in early identification and treatment of increased ICP. This article intends to identify those patients at risk of intracranial hypertension and present a framework for the emergency department investigation and treatment, in keeping with contemporary guidelines. Intensive care management and the treatment of refractory increases in ICP are also outlined. PMID- 22307195 TI - Pediatric emergency medicine: legal briefs. PMID- 22307196 TI - ECGs in the ED. PMID- 22307197 TI - Methodology to account for uncertainties and tradeoffs in pharmaceutical environmental hazard assessment. AB - Many pharmaceutical products find their way into receiving waters, giving rise to concerns regarding their environmental impact. A procedure was proposed that enables ranking of the hazard to aquatic species and human health due to such products. In the procedure, hazard assessment is based on five of the pharmaceutical product's individual physico-chemical properties. These properties are aggregated using the weighted Euclidian distance as the utility function. The weights and physico-chemical properties are considered as random variables. Physico-chemical property uncertainty criteria are obtained from a literature review. Weight uncertainty is based on a hazard ranking from a panel of experts, the histogram of which is converted into a continuous probability density function using statistical Kernel smoothing technique. The hazard-ranking procedure was applied to a list of common pharmaceuticals used in Switzerland. The procedure is target-specific. Two rankings were presented: One giving priority to environmental protection and the other to human health. For most substances, the hazard rank depends on the target. For the Swiss case study, the ranking procedure led to the conclusion that the hormones ethinylestradiol and testosterone, along with the antibiotic erythromycin A, should be in all cases included in risk-assessment methodologies, environmental concentration estimates and regular measurement campaigns. The methodology proposed is flexible and can be extrapolated to other substances and groups of experts. PMID- 22307198 TI - [Purulent gonarthritis resulting from H1N1 viral pneumonia]. AB - No articles on orthopedic complications of pneumonia due to influenza A H1N1 virus have yet been published. A 44-year-old male patient was hospitalized due to the suspicion of an infected knee. During arthroscopy beta-hemolytic Streptococcus group A and Acinetobacter were found and the histopathological diagnosis of an infectious bacterial synovialitis was made. Despite resistance oriented antibiotic treatment the patient's general condition worsened. Influenza A H1N1 virus was detected in a nasal sample and was successfully treated with Tamiflu(r). If fever and elevated infection markers persist a search for the focus has to be performed including unlikely diseases such as influenza A H1N1 virus. PMID- 22307199 TI - Deciphering the enigma of lignification: precursor transport, oxidation, and the topochemistry of lignin assembly. AB - Plant lignification is a tightly regulated complex cellular process that occurs via three sequential steps: the synthesis of monolignols within the cytosol; the transport of monomeric precursors across plasma membrane; and the oxidative polymerization of monolignols to form lignin macromolecules within the cell wall. Although we have a reasonable understanding of monolignol biosynthesis, many aspects of lignin assembly remain elusive. These include the precursors' transport and oxidation, and the initiation of lignin polymerization. This review describes our current knowledge of the molecular mechanisms underlying monolignol transport and oxidation, discusses the intriguing yet least-understood aspects of lignin assembly, and highlights the technologies potentially aiding in clarifying the enigma of plant lignification. PMID- 22307200 TI - Multiple-reaction monitoring-mass spectrometric assays can accurately measure the relative protein abundance in complex mixtures. AB - BACKGROUND: Mass spectrometric assays could potentially replace protein immunoassays in many applications. Previous studies have demonstrated the utility of liquid chromatography-multiple-reaction monitoring-mass spectrometry (LC MRM/MS) for the quantification of proteins in biological samples, and many examples of the accuracy of these approaches to quantify supplemented analytes have been reported. However, a direct comparison of multiplexed assays that use LC-MRM/MS with established immunoassays to measure endogenous proteins has not been reported. METHODS: We purified HDL from the plasma of 30 human donors and used label-free shotgun proteomics approaches to analyze each sample. We then developed 2 different isotope-dilution LC-MRM/MS 6-plex assays (for apoliporoteins A-I, C-II, C-III, E, B, and J): 1 assay used stable isotope labeled peptides and the other used stable isotope-labeled apolipoprotein A-I (an abundant HDL protein) as an internal standard to control for matrix effects and mass spectrometer performance. The shotgun and LC-MRM/MS assays were then compared with commercially available immunoassays for each of the 6 analytes. RESULTS: Relative quantification by shotgun proteomics approaches correlated poorly with the 6 protein immunoassays. In contrast, the isotope dilution LC MRM/MS approaches showed correlations with immunoassays of r = 0.61-0.96. The LC MRM/MS approaches had acceptable reproducibility (<13% CV) and linearity (r >=0.99). Strikingly, a single protein internal standard applied to all proteins performed as well as multiple protein-specific peptide internal standards. CONCLUSIONS: Because peak area ratios measured in multiplexed LC-MRM/MS assays correlate well with immunochemical measurements and have acceptable operating characteristics, we propose that LC-MRM/MS could be used to replace immunoassays in a variety of settings. PMID- 22307201 TI - Rehabilitation of reading and visual exploration in visual field disorders: transfer or specificity? AB - Reading and visual exploration impairments in unilateral homonymous visual field disorders are frequent and disabling consequences of acquired brain injury. Compensatory therapies have been developed, which allow patients to regain sufficient reading and visual exploration performance through systematic oculomotor training. However, it is still unclear whether the reading and visual exploration impairments require specific compensatory training for their improvement. We present the first cross-over rehabilitation study to determine whether the training-related performance improvements are task-specific, or whether there is a transfer of training-related improvements between reading and visual exploration. We compared the therapeutic effects of compensatory oculomotor reading and visual exploration training in 36 patients with unilateral homonymous visual field loss in a cross-over design. In addition, we explored whether the training sequence determines the overall treatment outcome. Our findings demonstrate that the training-related improvements in reading and visual exploration are highly specific and task-dependent, and there was no effect of training sequence. PMID- 22307202 TI - High dose 1,25(OH)2D3 inhibits osteoblast mineralization in vitro. AB - Vitamin D is essential for optimal calcium absorption needed for maintaining normal bone mineral density (BMD). Consequently, vitamin D-deficiency leads to poorly mineralized bone with diminished strength and load bearing capacity. Surprisingly, several animal and clinical studies have identified suppressive effects of high dose vitamin D supplementation on bone formation. These data suggest that while vitamin D is necessary for basal bone homeostasis, excessive concentrations may be detrimental to the skeleton. To further examine the direct effects of high dose vitamin D on the function of osteoblasts we differentiated primary osteoblast precursors and MC3T3 preosteoblastic cells, in the presence of supraphysiological doses of the active metabolite, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. In vitro osteoblast mineralization was potently suppressed by high dose 1,25(OH)2D3. To investigate the mechanism we used a bioassay to examine nuclear factor-kappaB (NF-kappaB) activation in MC3T3 cells. Although NF-kappaB agonists are generally potent inhibitors of osteoblast differentiation, surprisingly, 1,25(OH)2D3 dose-dependently suppressed, rather than stimulated, NF kappaB activation. Interestingly, 1,25(OH)2D3 also suppressed Smad activation induced by the osteoblast commitment and differentiation factors transforming growth factor-beta (TGF-beta) and bone morphogenetic protein 2 (BMP2), which may account for the inhibitory activities of 1,25(OH)2D3 on mineralization. Our data suggest that vitamin D has complex pleiotropic effects on osteoblast signal transduction. As the net balance of high dose 1,25(OH)2D3 appears to be an inhibitory action on osteoblasts, our data suggest that the therapeutic value of vitamin D to maximize bone mass through indirect actions on calcium absorption may need to be carefully balanced with potential inhibitory direct effects on mineralizing cells. Our data suggest that indiscriminate over-dosing may be detrimental to bone formation and optimal concentrations need to be established for humans in vivo. PMID- 22307203 TI - An aptamer based on-plate microarray for high-throughput insulin detection by MALDI-TOF MS. AB - An aptamer microarray was directly fabricated on a MALDI target plate for high throughput insulin detection. High sensitivities were observed both in standard solutions (5 ng mL(-1), 0.86 nM) and serum sample (20 ng mL(-1), 3.4 nM). This method shows great promise in the field of biomarker detection. PMID- 22307204 TI - Phylogenetic comparison among the heterocystous cyanobacteria based on a polyphasic approach. AB - Phylogenetic comparison has been done among the selected heterocystous cyanobacteria belonging to the sections IV and V. The hierarchical cluster analysis based on antibiotics sensitivity showed a distant relationship between the members of Nostocales and Stigonematales. Thus, multiple antibiotic resistance pattern used as marker provide easy, fast, and reliable method for strain discrimination and genetic variability. However, morphological, physiological (both based on principal component analysis) and biochemical analysis grouped true branching cyanobacteria along with the members of section IV. Molecular analysis based on 16S rRNA gene sequences revealed that Hapalosiphon welwitschii and Westiellopsis sp. were grouped in cluster I whereas Scytonema bohnerii, a false branching genera showed a close proximity with Calothrix brevissima in cluster II. Cluster III of clade 2 included Nostoc calcicola and Anabaena oryzae which proved the heterogeneity at the generic level. Cluster IV the largest group of clade 2 based on 16S rRNA gene sequences includes six strains of the genera Nostoc, Anabaena, and Cylindrospermum showing ambiguous evolutionary relationship. In cluster IV, Anabaena sp. and Anabaena doliolum were phylogenetically linked by sharing 99% sequence similarity. Probably, they were of the same genetic makeup but appear differently under the diverse physiological conditions. Section IV showed polyphyletic origin whereas section V showed monophyletic origin. Results suggested that either morphological or physiological or biochemical or molecular attribute is not sufficient to provide true diversity and phylogeny of the cyanobacteria at the generic level and thus, a polyphasic approach would be more appropriate and reliable. PMID- 22307206 TI - R2R3 MYB transcription factors: key regulators of the flavonoid biosynthetic pathway in grapevine. AB - Flavonoids compose one of the most abundant and important subgroups of secondary metabolites with more than 6,000 compounds detected so far in higher plants. They are found in various compositions and concentrations in nearly all plant tissues. Besides the attraction of pollinators and dispersers to fruits and flowers, flavonoids also protect against a plethora of stresses including pathogen attack, wounding and UV irradiation. Flavonoid content and composition of fruits such as grapes, bilberries, strawberries and apples as well as food extracts such as green tea, wine and chocolate have been associated with fruit quality including taste, colour and health-promoting effects. To unravel the beneficial potentials of flavonoids on fruit quality, research has been focused recently on the molecular basis of flavonoid biosynthesis and regulation in economically important fruit-producing plants such as grapevine (Vitis vinifera L.). Transcription factors and genes encoding biosynthetic enzymes have been characterized, studies that set a benchmark for future research on the regulatory networks controlling flavonoid biosynthesis and diversity. This review summarizes recent advances in the knowledge of regulatory cascades involved in flavonoid biosynthesis in grapevine. Transcriptional regulation of flavonoid biosynthesis during berry development is highlighted, with a particular focus on MYB transcription factors as molecular clocks, key regulators and powerful biotechnological tools to identify novel pathway enzymes to optimize flavonoid content and composition in grapes. PMID- 22307207 TI - Inducible growth mode switches influence Valonia rhizoid differentiation. AB - Cell differentiation and cell type commitment are an integral part of plant growth and development. Investigations on how environmental conditions affect the formation of shoots, roots, and rhizoids can help illustrate how plants determine cell fate and overall morphology. In this study, we evaluated the role of substratum and light on rhizoid differentiation in the coenocytic green alga, Valonia aegagropila. Elongating rhizoids displayed varying growth modes and cell shape upon exposure to different substrata and light conditions. It was found that soft substrata and dark incubation promoted rhizoid elongation via tip growth while subsequent exposure to light prevented tip growth and instead induced swelling in the apical region of rhizoids. Swelling was accompanied by the accumulation of protoplasm in the rhizoid tip through expansion of the cell wall and uninhibited cytoplasmic streaming. Subsequent diffuse growth led to the transformation from slender, rod-shaped rhizoids into spherical thallus-like structures that required photosynthesis. Further manipulation of light regimes caused vacillating cell growth redirections. An elongating V. aegagropila rhizoid cell thus appears capable of growth mode switching that is regulated by immediate environmental conditions thereby influencing ultimate cell shape and function. This is the first description of inducible, multiple growth mode shifts in a single intact plant cell that directly impact its differentiation. PMID- 22307208 TI - Protein farnesylation and disease. AB - Prenylation consists of the addition of an isoprenoid group to a cysteine residue located near the carboxyl terminal of a protein. This enzymatic posttranslational modification is important for the maturation and processing of proteins. Both processes are necessary to mediate protein-protein and membrane-protein associations, in addition to regulating the localisation and function of proteins. The severe phenotype of animals deficient in enzymes involved in both prenylation and maturation highlights the significance of these processes. Moreover, alterations in the genes coding for isoprenylated proteins or enzymes that are involved in both prenylation and maturation processes have been found to be the basis of severe human diseases, such as cancer, neurodegenerative disorders, retinitis pigmentosa, and premature ageing syndromes. Recent studies on isoprenylation and postprenylation processing in pathological conditions have unveiled surprising aspects of these modifications and their roles in different cellular pathways. The identification of these enzymes as therapeutic targets has led researchers to validate their effects in vitro and in vivo as antitumour or antiageing agents. This review attempts to summarise the basic aspects of protein isoprenylation and postprenylation, integrating our data with that observed in other studies to provide a comprehensive scenario of progeroid syndromes and the therapeutic avenues. PMID- 22307209 TI - Single dose NTBC-treatment of hereditary tyrosinemia type I. AB - NTBC (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3cyclohexanedione) is the mainstay of treatment in tyrosinemia type 1 (HT 1). The current recommendation is to divide the total daily dose of NTBC into two doses. We monitored the plasma NTBC concentrations in a series of seven patients who were changed from multiple divided doses to a single daily dose of NTBC. Two additional patients were started on a single daily dose of NTBC after the diagnosis of HT 1 was established. In three patients, NTBC kinetics were performed over 6 and 24 hours, respectively. The use of multiple divided doses or a single daily dose did not significantly affect plasma NTBC concentrations or the mean daily dose needed to attain therapeutic plasma NTBC concentrations. Moreover, kinetic studies demonstrated that plasma NTBC concentrations were completely stable over a period of 24 hours with a single dose regimen, as expected given the known NTBC plasma half life of 54 hours. Although these preliminary results need to be confirmed in more patients, our findings show that administration of NTBC in a single daily dose may be as effective as a multiple-dose regimen in reaching therapeutic plasma NTBC concentrations and suppressing succinylacetone formation in patients with HT 1. In fact, single dose treatment may increase patients' compliance with the drug treatment and improve metabolic control. PMID- 22307210 TI - Transperineal template-guided mapping biopsy as a staging procedure to select patients best suited for active surveillance. AB - OBJECTIVES: Patients with clinically insignificant prostate cancer are candidates for active surveillance. However, uncertainty regarding the true extent of disease limits enthusiasm. In this study, we report our initial findings in patients with transrectal ultrasound (TRUS)-detected clinically insignificant prostate cancer undergoing transperineal template-guided mapping biopsy (TTMB) as a staging procedure. METHODS: Sixty-four patients who met the Epstein criteria for clinically insignificant prostate cancer underwent TTMB. Each biopsy core position was recorded in 3 dimensions with documentation of location of each positive biopsy core, Gleason score, percentage of involvement of each core, and presence/absence of perineural invasion. RESULTS: Mean pre-TRUS prostate specific antigen was 4.7 ng/mL with a Gleason score of 6 involving a median of 5% of 1 TRUS core. The mean number of TTMB biopsy cores was 58.5, with 6.6 cores positive for malignancy. Ten patients had clinically insignificant prostate cancer (15.7%), 8 had no TTMB-detected cancer (12.5%), and 46 (71.9%) had clinically significant cancer. Of patients with cancer, 37 (66.1%) had bilobar involvement and 25 (44.6%) harbored a Gleason score of >=7. In a multivariate analysis, tobacco consumption was found to be most closely related to clinically significant disease on TTMB. CONCLUSIONS: TRUS biopsy underestimates disease extent and Gleason score in some patients. TTMB provides a more accurate assessment of the presence of aggressive histology. PMID- 22307211 TI - Clinical cancer genetics. Part 2: Breast. AB - Since the discovery of proven genetic mutations which predispose people to breast cancer along with the routine availability of genetic testing for such mutations, a number of issues have surfaced regarding potential methods of breast cancer diagnosis, surveillance, treatment, and risk reduction. Many of these issues pertain to the practice of radiation oncology and can affect decisions on management. This article aims to describe some of the more salient features of individuals at high genetic risk for breast developing cancer along with aspects of their tumor biology, clinical natural history, and how the radiation oncologist may address these challenges. PMID- 22307212 TI - Formal statistical testing and inference in randomized phase II trials in medical oncology. AB - OBJECTIVES: With the growing number of new anticancer therapies, randomized phase II trials have been used more often in oncology. Although the primary objective of such trials is not to formally compare results between arms, this practice seems frequent. We sought to quantify the frequency of use of formal statistical testing or inference through the use of P values and confidence intervals (CIs) in randomized phase II trials. METHODS: We searched PubMed for randomized phase II trials assessing systemic cancer therapies published in the years 1995/1996 and 2005/2006. For each study, 2 reviewers independently abstracted data, including reporting of P values and CIs for the primary endpoint. RESULTS: We retrieved 288 articles, 107 of which were eligible for analysis. The median number of patients per trial was 94, the primary endpoint was response rate in 71 (66.4%) cases, and a control arm was present in 55 (51.4%) trials. Either P values or CIs for the primary endpoint were reported in 85 (79.4%; 95% CI, 70.8% 86.1%) cases. Year of publication, source of funding, and use of a control group were not associated with this practice. CONCLUSIONS: Formal statistical comparisons between arms of randomized phase II trials are frequently undertaken in medical oncology. The extent to which such a practice abrogates phase III testing is unknown. PMID- 22307213 TI - A phase II trial of nab-Paclitaxel as second-line therapy in patients with advanced pancreatic cancer. AB - OBJECTIVE: nab-Paclitaxel has been shown to disrupt pancreatic cancer stroma and was effective in combination with gemcitabine in a phase I/II trial. This study was designed to determine the efficacy of nab-paclitaxel monotherapy in previously treated pancreatic cancer patients. METHODS: In this phase II trial, patients with advanced pancreatic cancer who progressed on gemcitabine-based therapy, received nab-paclitaxel 100 mg/m over 30 minutes on days 1, 8, and 15 of a 28-day cycle. The primary endpoint was 6-month overall survival (OS). Secondary endpoints were response rate (by Response Evaluation Criteria In Solid Tumors), progression-free survival, safety, and toxicity profile. RESULTS: Among 19 patients treated, the median age was 61 years, 9 (47%) were male patients and 18 (95%) had stage-IV disease. The primary endpoint of the study was reached with a 6-month OS of 58% [95% confidence interval (95% CI), 33%-76%] and an estimated median OS of 7.3 months (95% CI, 2.8-15.8 mo). The median progression-free survival was 1.7 months (95% CI, 1.5-3.5 mo). One patient had a confirmed partial response and 6 (32%) had stable disease as their best response. Nonhematological toxicities were generally mild with grades 1-2 nausea, anorexia, hypocalcemia, and vomiting occurring in 63%, 47%, 37%, and 26% of patients, respectively. Grades 3-4 neutropenia, neutropenic fever, and anemia occurred in 32%, 11%, and 11% of patients, respectively. Only 2 of 15 available tumors stained positive for secreted protein acid rich in cysteine, and neither of these patients benefited from the therapy. CONCLUSIONS: nab-Paclitaxel was well tolerated, and it demonstrated preliminary evidence of activity in a subset of patients who progressed on gemcitabine-based therapy. PMID- 22307214 TI - Impact of a prostate multidisciplinary clinic program on patient treatment decisions and on adherence to NCCN guidelines: the William Beaumont Hospital experience. AB - OBJECTIVES: In order to demonstrate the impact of multidisciplinary care in the community oncology setting, we evaluated treatment decisions after the initiation of a dedicated prostate and genitourinary (GU) multidisciplinary clinic (MDC). METHODS: In March 2010, a GU MDC was created at William Beaumont Hospital with the goal of providing patients with a comprehensive multidisciplinary evaluation and consensus treatment recommendations in a single visit. Urologists, radiation, and medical oncologists along with ancillary support staff participated in this comprehensive initial evaluation. The impact of this experience on patient treatment decisions was analyzed. RESULTS: During the first year, a total of 182 patients were seen. Compared with previous years, low-risk MDC patients more frequently chose external beam radiation therapy (41.1% vs. 26.6%, P=0.02), and active surveillance (14.3% vs. 6.1%, P=0.02) and less frequently prostatectomy (30.4% vs. 44.0%, P=0.03). Similar increases in external beam were seen in intermediate and high-risk patients. Increased use of hormonal therapy was found in high-risk patients compared with the years before the initiation of the MDC (76.2% vs. 51.1%, P=0.03). Increased adherence to National Comprehensive Cancer Network (NCCN) guidelines was seen with intermediate-risk patients (89.8% vs. 75.9%, P=0.01), whereas nonsignificant increases were seen in low-risk (100% vs. 98.9%, P=0.43) and high-risk patients (100% vs. 94.2%, P=0.26). CONCLUSIONS: The establishment of a GU MDC improved the quality of care for cancer patients as demonstrated by improved adherence to National Comprehensive Cancer Network guidelines, and a broadening of treatment choices made available. PMID- 22307215 TI - Acceptability of cervical cancer screening in rural Mozambique. AB - In Zambezia province, Mozambique, cervical cancer (CC) screening was introduced to rural communities in 2010. Our study sought to determine whether women would accept screening via pelvic examination and visual inspection with acetic acid (VIA) at two clinical sites near the onset of a new CC screening program. A cross sectional descriptive study of 101 women was undertaken in two rural communities in north-central Mozambique. We assessed a woman's willingness to be screened, knowledge about CC symptoms and treatment, and her recommendations for best methods to deliver information to other women. After the interview, we offered CC screening. Fully 86% of women accepted VIA screening when it was offered, but uptake was 100% at one clinic and only 68% at another. The cause of CC was thought to be associated with promiscuous activity (49%) and curses placed on the woman (42%). All women in one rural Mozambique clinic and two-thirds at a second clinic underwent CC screening. Knowledge about CC screening was significantly associated with uptake, suggesting educational campaigns need to be undertaken. However, educators need to be cautious about linking screening with high-risk behaviors, as women who understood the link trended toward refusing screening. PMID- 22307216 TI - Pharmacokinetics of memantine in rats and mice. PMID- 22307217 TI - Mechanisms involved in biological behavior changes associated with Angptl4 expression in colon cancer cell lines. AB - Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths throughout the world. Angiopoietin-like-4 (Angptl4), a member of the angiopoietin family of secreted proteins, is frequently expressed in the perinecrotic areas of different human tumors, yet its role is still unclear in colorectal cancer. Angptl4 mRNA expression in primary colorectal cancer tissue and seven colon cancer cell lines was measured by semi-quantitative RT-PCR; the influence of Angptl4 expression on the colon cancer cell lines was investigated by either overexpression or knockdown of Angptl4 in colon cancer cell lines HCT116 and HT29, respectively. The results showed that Angptl4 mRNA is frequently expressed in human colorectal cancer tissues and cell lines. Overexpression of Angptl4 promoted cell migration, F-actin reorganization and formation of pseudopodia. Further investigation showed that high Angptl4 expression was associated with an increase in ezrin/radixin/moesin and vasodilator-stimulated phosphoprotein expression and a decrease in E-cadherin expression. These results indicate that overexpression of Angptl4 may promote invasion and metastasis in CRC. PMID- 22307218 TI - Functionalized corannulene cations: a detailed theoretical survey. AB - The first theoretical investigation of a series of surface-decorated corannulene cations, {R-C(20)H(10)}(+), where R = H, CH(3), CH(2)Cl, CHCl(2), and CCl(3), is accomplished. Three possible isomers of {R-C(20)H(10)}(+) such as hub-, rim-, and spoke-functionalized corannulene derivatives are considered and compared. The trends in their stability and transition barriers are provided. A detailed study of energetics of {R-C(20)H(10)}(+) is complemented by in-depth investigation of their electronic structures and aromaticity. PMID- 22307219 TI - Quantitative analysis of acylated oleanane-type triterpene saponins, chakasaponins I-III and floratheasaponins A-F, in the flower buds of Camellia sinensis from different regional origins. AB - A quantitative analytical method was developed for the determination of acylated oleanane-type triterpene saponins, chakasaponins I-III (1-3) and floratheasaponins A-F (4-9), found in Camellia sinensis (Theaceae). The practical conditions for separation and detection of these saponins were established on an ODS column with methanol containing 5 mM trifluoroacetic acid as a mobile phase, and the detection and quantitation limits of the method were estimated to be 1.1 3.8 and 3.5-12.5 ng, respectively. The relative standard deviation values of intra- and interday precision were lower than 2.35 and 6.12%, respectively, overall mean recoveries of all saponins being 94.7-108.8%, and the correlation coefficients of all the calibration curves showed good linearity within the test ranges. To approve the validity of the protocol, extracts of 13 kinds of C. sinensis collected in China, Taiwan, Japan, and India were evaluated. The results indicated that the assay was reproducible and precise, and could be readily utilized for the quality evaluation of tea flowers. It was noteworthy that the distinct regional difference was observed with respect to the content of chakasaponins and floratheasaponins, more chakasaponins being contained in the extracts of tea flowers from Fujian and Sichuan provinces, China than those from Japan, Taiwan, and India. Optimum conditions for the extraction process were also established. PMID- 22307220 TI - Bilateral same-day intravitreal injections using a single vial and molecular bacterial screening for safety surveillance. AB - PURPOSE: To evaluate the safety of bilateral same-day intravitreal injections using a single vial and to introduce a molecular surveillance system to screen bacterial drug contamination using eubacterial polymerase chain reaction (PCR). METHODS: Retrospective review of the medical records of 135 patients who received 574 bilateral same-day intravitreal injections for various retinal diseases in 2 tertiary referral hospitals between January 2008 and March 2010 was performed. Data were obtained regarding the diagnosis, kinds of drugs injected, postinjection complications, and the result of molecular bacterial screening of the injected drugs. Drugs for bilateral intravitreal injections were drawn from a single vial and injected using separate syringes or needles. Molecular bacterial screening was performed using the remaining drug in the syringe by 16S ribosomal DNA real-time PCR. RESULTS: A total of 574 injections (384 bevacizumab, 154 ranibizumab, and 36 triamcinolone) were administered on bilateral eyes of 135 patients. There were no complications, including endophthalmitis, uveitis, retinal tear, or retinal detachment. Of the 278 injections screened for bacterial contamination using eubacterial PCR, no cases (0%) showed drug contamination by bacteria. The sensitivity of eubacterial PCR for molecular bacterial screening was 10 colony-forming units (CFUs)/mL or lower. CONCLUSION: Bilateral same-day intravitreal injections drawn from a single vial using separate syringes or needles are well tolerated by patients, and its safety profile may be equivalent to unilateral injections. The bacterial molecular surveillance system using eubacterial PCR demonstrated the safety of bilateral same-day intravitreal injections and may be used for safety surveillance and for timely intervention of possible drug-related endophthalmitis. PMID- 22307222 TI - Charge photogeneration in hybrid solar cells: a comparison between quantum dots and in situ grown CdS. AB - We demonstrate that blend films containing poly(3-hexylthiophene-2,5-diyl) and in situ grown CdS display a greater yield of photogenerated charges than a blend containing an equivalent amount of pre-synthesised CdS quantum dots. Moreover, we show that the greater charge yield in the in situ grown films leads to an improvement in device efficiency. The present findings also appear to suggest that charge photogeneration at the CdS/polymer heterojunction is facilitated by the formation of nanoparticle networks as a result of CdS aggregation. PMID- 22307223 TI - The sourdough fermentation may enhance the recovery from intestinal inflammation of coeliac patients at the early stage of the gluten-free diet. AB - PURPOSE: This study aimed at investigating the effect of corn, rice and amaranth gluten-free (GF) sourdoughs on the release of nitric oxide (NO) and synthesis of pro-inflammatory cytokines by duodenal mucosa biopsies of eight coeliac disease (CD) patients. METHODS: Selected lactic acid bacteria were used as starters for the manufacture of corn, rice or amaranth sourdoughs. Chemically acidified doughs, without bacterial starters, and doughs started with baker's yeast alone were also manufactured from the same GF matrices. Pepsin-trypsin (PT) digests were produced from all sourdoughs and doughs, and used to assay the rate of recovery of biopsy specimens from eight CD patients at diagnosis. The release of NO and the synthesis of pro-inflammatory cytokines interferon-gamma (IFN-gamma) were assayed. RESULTS: During fermentation, lactic acid bacteria acidified and grew well (ca. log 9.0 CFU/g) on all GF matrices, showing intense proteolysis. Duodenal biopsy specimens still released NO and IFN-gamma when subjected to treatments with basal medium (control), PT-digest from chemically acidified doughs and PT-digest from doughs fermented with baker's yeast alone. On the contrary, the treatment of all the biopsy specimens with PT-digests from all GF matrices subjected to sourdough fermentation significantly decreased the release of NO and the synthesis of IFN-gamma. CONCLUSIONS: During manufacture of GF baked goods, the use of sourdough fermentation could be considered as an adjuvant to enhance the recovery from intestinal inflammation of coeliac patients at the early stage of the gluten-free diet. PMID- 22307224 TI - MOP-phosphonites: a novel ligand class for asymmetric catalysis. AB - Chiral phosphonite ligands (S,R(b))-5a, (S,S(b))-5b, (R,R(b))-6a and (R,S(b))-6b are introduced, comprising a MOP-type backbone with a binol-based binaphthyl group bound to the phosphorus. Their reaction with [Pd(eta(3)-C(4)H(7))Cl](2) affords eta(3)-methallylpalladium chloride complexes 7a/b and 8a/b which have been isolated and structurally characterised. Solid-state and solution studies indicate subtle differences in their coordination behaviour, which ultimately affects their efficacy in the asymmetric hydrosilylation of styrene. PMID- 22307225 TI - Unlicensed and off-label drug use in hospitalized children in Croatia: a cross sectional survey. AB - PURPOSE: The aim of this study was to determine the prevalence and pattern of unlicensed and off-label drugs prescribed to hospitalized children at the Department of Paediatrics, University Hospital Rijeka, Croatia. METHODS: A prospective cross-sectional study was performed on 1 day each month during a 12 month period and included all hospitalized children and adolescents. RESULTS: A total of 1,643 prescriptions for 198 different drugs were prescribed to 531 out of 691 (77%) hospitalized patients. Forty-six percent of the different drugs were prescribed in an unlicensed or off-label manner. Of all drug prescriptions, 25% were either unlicensed or off-label. Forty-eight percent of the patients received either an unlicensed or off-label drug. The most frequently prescribed off-label drugs were proton pump inhibitors. CONCLUSION: Unlicensed and off-label drug use is common. It is not illegal and may be clinically appropriate but is associated with a number of clinical, safety, and ethical issues. Regulatory authorities should use existing clinical evidence on the use of off-label and unlicensed drugs in decision making. Marketing authorization holders and national regulatory authorities should monitor for any safety concerns associated with unlicensed and off-label drug use and take appropriate measures as well as identify research priorities and mandate clinical studies to resolve important questions. PMID- 22307226 TI - Association between multi-dose drug dispensing and drug treatment changes. AB - PURPOSE: To compare drug treatment changes in older hip fracture patients with and without multi-dose drug dispensing (MDD) after discharge from hospital. METHODS: Hip fracture patients (aged 65 years or older) for whom the same prescribing procedure was used at discharge and at the 6-month follow-up were extracted from two patient cohorts consecutively recruited in 2008 (n = 100) and 2009 (n = 99), respectively. Of these hip fracture patients, 107 patients used MDD and 47 used ordinary prescriptions (OP) throughout the study period. Drug treatment was registered at discharge and at the 6-month follow-up. Each drug was classified as changed (withdrawn, dosage adjusted or added) or unchanged. The association between MDD and changes in drug treatment was analysed with generalised estimating equations (GEE). Age, sex, cognition, year of study and type of drug (fall-risk-increasing, fracture-preventing or other) were included in the model. RESULTS: A total of 1,980 drugs were prescribed at discharge and at the 6-month follow-up to the 154 patients. Of the 1,413 drugs prescribed via MDD, 597 (43%) drugs were unchanged. The corresponding figure for drugs prescribed via OP was 166 out of 567 (29%) prescribed drugs. Analysis with GEE revealed an odds ratio (95% confidence interval) of 1.66 (1.20-2.31) to 1.77 (1.38-2.27) for a drug to be classified as unchanged when prescribed via the MDD system. CONCLUSIONS: MDD is associated with fewer changes in drug treatment compared with OP. Further studies of risks and benefits from this prescribing procedure are urged. PMID- 22307227 TI - Preclinical activity of LBH589 alone or in combination with chemotherapy in a xenogeneic mouse model of human acute lymphoblastic leukemia. AB - Histone deacetylases (HDACs) have been identified as therapeutic targets due to their regulatory function in chromatin structure and organization. Here, we analyzed the therapeutic effect of LBH589, a class I-II HDAC inhibitor, in acute lymphoblastic leukemia (ALL). In vitro, LBH589 induced dose-dependent antiproliferative and apoptotic effects, which were associated with increased H3 and H4 histone acetylation. Intravenous administration of LBH589 in immunodeficient BALB/c-RAG2(-/-)gammac(-/-) mice in which human-derived T and B ALL cell lines were injected induced a significant reduction in tumor growth. Using primary ALL cells, a xenograft model of human leukemia in BALB/c-RAG2(-/ )gammac(-/-) mice was established, allowing continuous passages of transplanted cells to several mouse generations. Treatment of mice engrafted with T or B-ALL cells with LBH589 induced an in vivo increase in the acetylation of H3 and H4, which was accompanied with prolonged survival of LBH589-treated mice in comparison with those receiving vincristine and dexamethasone. Notably, the therapeutic efficacy of LBH589 was significantly enhanced in combination with vincristine and dexamethasone. Our results show the therapeutic activity of LBH589 in combination with standard chemotherapy in pre-clinical models of ALL and suggest that this combination may be of clinical value in the treatment of patients with ALL. PMID- 22307228 TI - Transforming growth factor-beta1 induces glutathione peroxidase-1 and protects from H2O2-induced cell death in colon cancer cells via the Smad2/ERK1/2/HIF 1alpha pathway. AB - Recent studies have shown that transforming growth factor-beta1 (TGF-beta1) signaling plays important roles in the redox system in benign and malignant cells. Whether TGF-beta mediates an antioxidative damage response in colorectal cancer cells is largely unknown. Herein, using the human colorectal cancer cell lines we found that TGF-beta1 induced glutathione peroxidase-1 (GPx-1) expression and enzyme activity, and that the upregulation of GPx-1 by TGF-beta1 could protect colorectal cell lines from H2O2-induced oxidation damage. Further, we used loss- and gain-function approaches to elucidate the underlying mechanism and found that TGF-beta1 induced GPx-1 through activation of the TGF-beta receptor type I (TGF-betaRI)/Smad2/extracellular-signal-regulated kinase 1/2 (ERK1/2)/hypoxia-inducible factor-1alpha (HIF-1alpha) signaling pathway. This cascade could be blocked by the TGF-betaRI inhibitor or ERK1/2 inhibitor. Taken together, our data demonstrated that TGF-beta1 induced GPx-1 expression and enzymatic activity via the TGF-betaRI/Smad2/ERK1/2/HIF-1alpha signaling pathway, suggesting a novel antioxidative protective function of TGF-beta1 in colorectal cancer cells. PMID- 22307229 TI - Interactions of acidic pharmaceuticals with human serum albumin: insights into the molecular toxicity of emerging pollutants. AB - Acidic pharmaceuticals such as diclofenac (DCF), clofibric acid (CA) and ketoprofen (KTP) have been detected frequently in environmental media. In order to reveal the toxicity of such emerging pollutants, their interactions with human serum albumin (HSA) were investigated by capillary electrophoresis, molecular spectrometry, and equilibrium dialysis. The binding constants and sites of these acidic pharmaceuticals with HSA were obtained. The thermodynamic parameters, e.g. enthalpy change and entropy change of these interactions were calculated to characterize that all the reactions resulted from hydrophobic and electrostatic interactions. The static quenching of the fluorescence of HSA was observed when interacted with acidic pharmaceuticals, indicating acidic pharmaceuticals bound to Tryptophan residue of HSA. The 3D fluorescence and circular dichroism confirmed that the secondary conformation of HSA changed after the interactions with the pharmaceuticals. At physiological condition, only 0.12 mM acidic pharmaceuticals reduced the binding of vitamin B(2) to HSA by 37, 30 and 21% for DCF, KTP and CA, respectively. This work provides an insight into non-covalent interactions between emerging contaminants and biomolecule, and is helpful for clarifying the toxic mechanism of such emerging contaminants. PMID- 22307230 TI - Anal apocrine carcinoma: a case report and literature review. AB - Apocrine carcinoma (AC) is an extremely rare skin appendage tumor, which is located at lower dermal and subcutaneous tissue. We report a case of an anal AC arising from an apocrine adenoma in the anal region, which is only the second case reported in this region. A 71-year-old male presented to clinic with soreness in the anal region for 6 weeks. An excisional biopsy was performed. Histologically, the lesion was poorly circumscribed, infiltrative, and was composed of small to medium sized glands extending to the surgical margins. There were centrally dilated large glands with duct-like openings into the mucosal surface. The larger central glands contain periodic acid-Schiff-positive eosinophilic acellular secretions. At the periphery, there were smaller glands with significant cytologic atypia and numerous mitoses. A diagnosis of AC was made making it the second case report of this very rare malignancy in this region. Although ACs usually do not have a fatal outcome, there have been case reports of distant metastases and even death from this disease, making histologic distinction of this malignancy from a benign apocrine adenoma important. Wide local excision is typically the treatment of choice, although Mohs micrographic surgery has also been used with similar success. PMID- 22307231 TI - Chronic cutaneous graft-versus-host disease simulating hypertrophic lupus erythematosus--a case report of a new morphologic variant of graft-versus-host disease. AB - The spectrum of clinical and histopathologic features associated with chronic graft-versus-host disease (GVHD) is broad, with recognized variants simulating scleroderma, lichen sclerosus, eosinophilic fasciitis, and de novo diffuse melanoderma. We report a case of a patient with multiple myeloma who presented approximately 1 year after his allogeneic hematopoietic stem cell transplantation with lesions of chronic lichenoid GVHD that harbored features of hypertrophic lupus erythematosus (LE) and that was initially mistaken for a superficial well differentiated squamous cell carcinoma (SCC). However, in 4 years of follow-up, the patient failed to develop any evidence of cutaneous or systemic LE, actinic damage, or SCC, and the lesions cleared with topical and systemic treatments appropriate for chronic GVHD. For proper interpretation of the histologic findings of GVHD, it is important for the dermatopathologist to be aware of unusual manifestations. Knowledge of the occurrence of hypertrophic LE and familiarity with its histologic features is also important to avoid an erroneous diagnosis of SCC in immunosuppressed patients. PMID- 22307232 TI - Anetodermic pilomatricoma: molecular characteristics and trauma in the development of its bullous appearance. AB - Pilomatricoma is a common benign neoplasm of the skin characterized by a solid cutaneous nodule of hair matrix origin. The anetodermal or lymphangiectatic variant of pilomatricoma is rare, and its bullous appearance is often associated with attenuated collagen and elastic fibrils and dilated lymphatic vessels in the overlying dermis. However, the tumors of anetodermic pilomatricoma have never been characterized at the molecular level, and the exact mechanism for their development is unknown. In this study, we evaluated histological and molecular features of a bullous pilomatricoma along with 5 control tumors and determined that tumors of both anetodermic and control pilomatricoma comprise similar molecular features, such as nuclear lymphoid enhancer binding factor 1 (LEF1) localization and the expression of keratins. In addition, we associated the development of the anetodermic pilomatricoma with mechanical trauma, scar tissue formation, and increased numbers of blood and lymphatic vessels. This study suggests that the development of the anetodermic form of pilomatricoma is unlikely to be associated with the intrinsic properties of the tumor but with the mechanical trauma that disrupts the dermal integrity and vascular microenvironment. PMID- 22307233 TI - Dilated lymphatic vessels in tufted angioma: a potential source of diagnostic confusion. AB - Tufted angioma (TA), an uncommon benign vascular tumor, has a variable clinical presentation, and histopathologic findings are a key component of diagnosis. The presence of lymphatic vessels suggestive of lymphangioma can occasionally be the predominant finding and cause diagnostic confusion. Nine biopsies from 7 cases of TA were studied to assess the frequency and distribution of lymphangioma-like areas. Specimens were also stained with D2-40, VEGF-A, GLUT-1, and HHV-8. In one biopsy, lymphangioma-like vessels were the main finding. In all other cases of TA, lymphatics were present in the stroma but were often overshadowed by tufts of capillaries. D2-40 highlighted the stromal lymphatics and partially stained the capillaries within tufts. VEGF-A showed diffuse nonspecific staining of epidermis and endothelial cells in all specimens. GLUT1 and HHV-8 staining were uniformly negative in all 9 specimens. Accurate diagnosis of TA has important clinical implications given its occasional association with Kasabach-Merritt phenomenon, and the presence of lymphangioma-like vessels in biopsies of vascular lesions is entirely compatible with TA. PMID- 22307234 TI - Iron-catalysed tandem cross-dehydrogenative coupling (CDC) of terminal allylic C(sp3) to C(sp2) of styrene and benzoannulation in the synthesis of polysubstituted naphthalenes. AB - A novel iron-catalysed tandem cross-dehydrogenative coupling and benzoannulation process was developed for the synthesis of biologically and synthetically important polysubstituted naphthalene derivatives from simple 1,2-aryl-propenes and styrenes in moderate to good yields. PMID- 22307235 TI - Ethics corner--inequality and injustice for some. PMID- 22307236 TI - Vitamin E and selenium do not decrease prostate cancer incidence: vitamin E may actually increase it. PMID- 22307237 TI - Periconceptional maternal micronutrient supplementation is associated with widespread gender related changes in the epigenome: a study of a unique resource in the Gambia. AB - In addition to the genetic constitution inherited by an organism, the developmental trajectory and resulting mature phenotype are also determined by mechanisms acting during critical windows in early life that influence and establish stable patterns of gene expression. This is the crux of the developmental origins of health and disease hypothesis that suggests undernutrition during gestation and infancy predisposes to ill health in later life. The hypothesis that periconceptional maternal micronutrient supplementation might affect fetal genome-wide methylation within gene promoters was explored in cord blood samples from offspring of Gambian women enrolled into a unique randomized, double blind controlled trial. Significant changes in the epigenome in cord blood DNA samples were further explored in a subset of offspring at 9 months. Gender-specific changes related to periconceptional nutritional supplementation were identified in cord blood DNA samples, some of which showed persistent changes in infant blood DNA samples. Significant effects of periconceptional micronutrient supplementation were also observed in postnatal samples which were not evident in cord blood. In this Gambian population, the increased death rate of individuals born in nutritionally poor seasons has been related to infection and it is of interest that we identified differential methylation at genes associated with defence against infection and immune response. Although the sample size was relatively small, these pilot data suggest that periconceptional nutrition in humans is an important determinant of newborn whole genome methylation patterns but may also influence postnatal developmental patterns of gene promoter methylation linking early with disease risk. PMID- 22307238 TI - Predicting kissing interactions in microRNA-target complex and assessment of microRNA activity. AB - MicroRNAs (miRNAs) are a class of short RNA molecules that play an important role in post-transcriptional gene regulation. Computational prediction of the miRNA target sites in mRNA is crucial for understanding the mechanism of miRNA-mRNA interactions. We here develop a new computational model that allows us to treat a variety of miRNA-mRNA kissing interactions, which have been ignored in the currently existing miRNA target prediction algorithms. By including all the different inter- and intra-molecular base pairs, this new model can predict both the structural accessibility of the target sites and the binding affinity (free energy). Applications of the model to a test set of 105 miRNA-gene systems show a notably improved success rate of 83/105. We found that although the binding affinity alone predicts the miRNA repression efficiency with a high success rate of 73/105, the structure in the seed region can significantly influence the miRNA activity. The method also allows us to efficiently search for the potent miRNA from a pool of miRNA candidates for any given gene target. Furthermore, extension of the method may enable predictions of the three-dimensional (3D) structures of miRNA/mRNA complexes. PMID- 22307239 TI - Picking ChIP-seq peak detectors for analyzing chromatin modification experiments. AB - Numerous algorithms have been developed to analyze ChIP-Seq data. However, the complexity of analyzing diverse patterns of ChIP-Seq signals, especially for epigenetic marks, still calls for the development of new algorithms and objective comparisons of existing methods. We developed Qeseq, an algorithm to detect regions of increased ChIP read density relative to background. Qeseq employs critical novel elements, such as iterative recalibration and neighbor joining of reads to identify enriched regions of any length. To objectively assess its performance relative to other 14 ChIP-Seq peak finders, we designed a novel protocol based on Validation Discriminant Analysis (VDA) to optimally select validation sites and generated two validation datasets, which are the most comprehensive to date for algorithmic benchmarking of key epigenetic marks. In addition, we systematically explored a total of 315 diverse parameter configurations from these algorithms and found that typically optimal parameters in one dataset do not generalize to other datasets. Nevertheless, default parameters show the most stable performance, suggesting that they should be used. This study also provides a reproducible and generalizable methodology for unbiased comparative analysis of high-throughput sequencing tools that can facilitate future algorithmic development. PMID- 22307240 TI - Metoclopramide for nausea and vomiting prophylaxis during and after Caesarean delivery: a systematic review and meta-analysis. AB - Nausea and vomiting occur commonly during and after Caesarean delivery (CD) performed under neuraxial anaesthesia. Metoclopramide is a prokinetic agent reported to be safe in parturients. This meta-analysis assesses the efficacy of metoclopramide for prophylaxis against intra- and postoperative nausea and vomiting (IONV and PONV) in parturients undergoing CD under neuraxial anaesthesia. We performed a literature search of MEDLINE (1966-2011), Cochrane Central Register of Controlled Trials, EMBASE (1947-2011), Google scholar, and CINAHL for randomized controlled trials which compared metoclopramide with placebo in women having CD under neuraxial anaesthesia. Eleven studies with 702 patients were included in the analysis. Administration of metoclopramide (10 mg) resulted in a significant reduction in the incidence of ION and IOV when given before block placement [relative risk (RR) (95% confidence interval, 95% CI)=0.27 (0.16, 0.45) and 0.14 (0.03, 0.56), respectively] or after delivery [RR (95% CI)=0.38 (0.20, 0.75) and 0.34 (0.18, 0.66), respectively]. The incidence of early (0-3 or 0-4 h) PON and POV [RR (95% CI)=0.47 (0.26, 0.87) and 0.45 (0.21, 0.93), respectively] and overall (0-24 or 3-24 h) PON (RR 0.69; 95% CI 0.52, 0.92) were also reduced with metoclopramide. Extra-pyramidal side-effects were not reported in any patient. In conclusion, this review suggests that metoclopramide is effective and safe for IONV and PONV prophylaxis in this patient population. Given the quality of the studies and the infrequent use of neuraxial opioids, these results should be interpreted with caution in current practice and further studies are needed to confirm those findings. PMID- 22307242 TI - Clinical validation of a continuous non-invasive haemodynamic monitor (CNAP™ 500) during general anaesthesia. AB - BACKGROUND: We conducted a prospective study to test the validity of a new continuous non-invasive blood pressure (NIBP) monitor (CNAP) (CNAPTM Monitor 500). METHODS: One hundred patients undergoing elective surgery under general anaesthesia were included in the study after informed written consent. The CNAP finger cuffs were placed on the fingers of one arm, an arterial catheter was inserted into the same arm and data were recorded simultaneously. Agreement between invasive arterial pressure (IAP) and blood pressure obtained by CNAP was compared using the Bland-Altman method for repeated measurements. The data from the first 50 patients (software V3.0) were used to improve the software of the CNAP (software V3.5), which was then evaluated in another 50 patients. We defined a clinically acceptable agreement according to the standards of the American Association for the Advancement of Medical Instrumentation for NIBP measurements [limits of agreement (LOA) +/- 15 mm Hg]. RESULTS: We analysed 524 878 paired measurements in 100 patients. The mean bias of the mean arterial pressure in the first 50 patients was -2.9 mm Hg (sd 10.6 mm Hg, LOA -23.7 to 17.9 mm Hg), and in the consecutive 50 patients (using software V3.5) the bias was -3.1 mm Hg (sd 9.5 mm Hg, LOA -21.6 to 15.4 mm Hg). CONCLUSIONS: The new CNAP monitor showed an agreement with the IAP that is promising but did not match our predefined criteria. PMID- 22307241 TI - Short small-interfering RNAs produce interferon-alpha-mediated analgesia. AB - BACKGROUND: There is increasing interest in RNA interference in pain research using the intrathecal route to deliver small-interfering RNA (siRNA). An interferon (IFN) response is a common side-effect of siRNA. However, the IFN response in the spinal cord after intrathecal administration of siRNA remains unknown. We hypothesized that high doses of siRNAs can elicit off-target analgesia via releasing IFN-alpha. We investigated the IFN response and its role in regulating pain sensitivity in the spinal cords after intrathecal administration of siRNAs. METHODS: Male Sprague-Dawley rats were given intrathecal injections of non-targeting (NT) siRNAs or IFN-alpha and tested for complete Freund's adjuvant (CFA)-induced mechanical allodynia and heat hyperalgesia. IFN-alpha in the spinal cord after injection of NT siRNAs was measured by western blotting and immunohistochemical staining. RESULTS: IFN-alpha was up-regulated in the spinal cord after intrathecal treatment of NT siRNAs. Intrathecal injection of NT siRNAs, at high doses of 10 or 20 MUg, reduced CFA induced inflammatory pain (P<0.05). Intrathecal application of IFN-alpha inhibited pain hypersensitivity in inflamed rats and produced analgesia in naive rats (P<0.05). Notably, the anti-nociceptive effects elicited by NT siRNAs and IFN-alpha were reversed by IFN-alpha neutralizing antibody and naloxone. CONCLUSIONS: Our data suggest that (i) intrathecal administration of high doses of siRNA (>= 10 MUg) induced up-regulation of IFN-alpha in the spinal cord and produced analgesic effects through IFN-alpha, and (ii) IFN-alpha's analgesic effect is mediated via opioid receptors. Caution must be taken to avoid IFN-alpha mediated analgesic effects of siRNAs in pain research. PMID- 22307243 TI - Cation ordering in the double tungstate LiFe(WO4)2. AB - Single crystals of lithium iron tungstate, LiFe(WO(4))(2), were obtained using a high-temperature solution growth method. The analysis was conducted using the monoclinic space group C2/c, with beta = 90.597 (2) degrees , giving R1 = 0.0177. The Li and Fe atoms lie on twofold axes. The structure can also be refined using the orthorhombic space group Cmcm, giving slightly higher residuals. The experimental value of beta and the residuals mitigate in favour of the monoclinic description of the structure. Calculated bond-valence sums for the present results are closer to expected values than those obtained using the results of a previously reported analysis of this structure. PMID- 22307244 TI - Magnesium, calcium and strontium salts of phenylacetic acid. AB - Three alkaline earth metal salts of phenylacetic acid were examined and all were found to have similar structural types to analogous salts of benzoic and halobenzoic acids. Thus, a synchrotron study shows that the cations in catena poly[[[tetraaquamagnesium(II)]-MU-phenylacetato-kappa(2)O:O'] phenylacetate], {[Mg(C(8)H(7)O(2))(H(2)O)(4)](C(8)H(7)O(2))}(n), form a one-dimensional coordination polymer that propagates through Mg-O-C-O-Mg interactions involving both crystallographically independent Mg centres (Z' = 2) and through translation along the a axis. The polymeric chains pack to give alternate inorganic layers and organic bilayers. The Ca and Sr species catena-poly[[[diaqua(phenylacetato kappa(2)O,O')calcium(II)]-MU(3)-phenylacetato-1':1:1''kappa(4)O:O,O':O'] monohydrate], {[Ca(C(8)H(7)O(2))(2)(H(2)O)(2)].H(2)O}(n), and catena poly[[[diaqua(phenylacetato-kappa(2)O,O')strontium(II)]-MU(3)-phenylacetato 1':1:1''kappa(4)O:O,O':O'] monohydrate], {[Sr(C(8)H(7)O(2))(2)(H(2)O)(2)].H(2)O}(n), are essentially isostructural. Both form one-dimensional coordination polymers through a carboxylate group that forms four M-O bonds. The polymeric chains propagate via 2(1) screw axes parallel to the b axis and are further linked in the bc plane by hydrogen bonding involving the non-metal-bound water molecule. Similarly to the Mg salt, both have inorganic layers that alternate with organic bilayers. PMID- 22307245 TI - Poly[[MU2-1,3-bis(pyridin-4-yl)propane](MU3-1,4-phenylenediacetato)cadmium]. AB - Solvothermal reaction between Cd(NO(3))(2), 1,4-phenylenediacetate (1,4-PDA) and 1,3-bis(pyridin-4-yl)propane (bpp) afforded the title complex, [Cd(C(10)H(8)O(4))(C(13)H(14)N(2))](n). Adjacent carboxylate-bridged Cd(II) ions are related by an inversion centre. The 1,4-PDA ligands adopt a cis conformation and connect the Cd(II) ions to form a one-dimensional chain extending along the c axis. These chains are in turn linked into a two-dimensional network through bpp bridges. The bpp ligands adopt an anti-gauche conformation. From a topological point of view, each bpp ligand and each pair of 1,4-PDA ligands can be considered as linkers, while the dinuclear Cd(II) unit can be regarded as a 6-connecting node. Thus, the structure can be simplified to a two-dimensional 6-connected network. PMID- 22307246 TI - A new polymorph of 1-ferrocenyl-3-(3-nitroanilino)propan-1-one. AB - Recrystallization of the title compound, [Fe(C(5)H(5))(C(14)H(13)N(2)O(3))], from a mixture of n-hexane and dichloromethane gave the new polymorph, denoted (I), which crystallizes in the same space group (P1) as the previously reported structure, denoted (II). The Fe-C distances in (I) range from 2.015 (3) to 2.048 (2) A and the average value of the C-C bond lengths in the two cyclopentadienyl (Cp) rings is 1.403 (13) A. As indicated by the smallest C-Cg1-Cg2-C torsion angle of 1.4 degrees (Cg1 and Cg2 are the centroids of the two Cp rings), the orientation of the Cp rings in (I) is more eclipsed than in the case of (II), for which the value was 15.3 degrees . Despite the pronounced conformational similarity between (I) and (II), the formation of self-complementary N-H...O hydrogen-bonded dimers represents the only structural motif common to the two polymorphs. In the extended structure, molecules of (I) utilize C-H...O hydrogen bonds and, unlike (II), an extensive set of intermolecular C-H...pi interactions. Fingerprint plots based on Hirshfeld surfaces are used to compare the packing of the two polymorphs. PMID- 22307247 TI - Poly[aqua[MU3-(pyridin-1-ium-3,5-diyl)diphosphonato-kappa3O:O':O''][MU2-(pyridin 1-ium-3,5-diyl)diphosphonato-kappa2O:O']calcium(II)]. AB - The rigid organic ligand (pyridine-3,5-diyl)diphosphonic acid has been used to create the title novel three-dimensional coordination polymer, [Ca(C(5)H(6)NO(6)P(2))(2)(H(2)O)](n). The six-coordinate calcium ion is in a distorted octahedral environment, formed by five phosphonate O atoms from five different (pyridin-1-ium-3,5-diyl)diphosphonate ligands, two of which are unique, and one water O atom. Two crystallographically independent acid monoanions, L1 and L2, serve to link metal centres using two different coordination modes, viz. eta(2)MU(2) and eta(3)MU(3), respectively. The latter ligand, L2, forms a strongly undulated two-dimensional framework parallel to the crystallographic bc plane, whereas the former ligand, L1, is utilized in the formation of one dimensional helical chains in the [010] direction. The two sublattices of L1 and L2 interweave at the Ca(2+) ions to form a three-dimensional framework. In addition, multiple O-H...O and N-H...O hydrogen bonds stabilize the three dimensional coordination network. Topologically, the three-dimensional framework can be simplified as a very unusual (2,3,5)-connected three-nodal net represented by the Schlafli symbol (4.8(2))(4.8(8).10)(8). PMID- 22307248 TI - Poly[tetraamminecopper(II) bis[tris(MU2-cyanido-kappa2C,N)dicuprate(I)]]: a unique Cu(I)-Cu(II) mixed-valence complex containing anionic cuprous cyanide layers and [Cu(NH3)4]2+ cations. AB - The title compound, {[Cu(NH(3))(4)][Cu(CN)(3)](2)}(n), features a Cu(I)-Cu(II) mixed-valence CuCN framework based on {[Cu(2)(CN)(3)](-)}(n) anionic layers and [Cu(NH(3))(4)](2+) cations. The asymmetric unit contains two different Cu(I) ions and one Cu(II) ion which lies on a centre of inversion. Each Cu(I) ion is coordinated to three cyanide ligands with a distorted trigonal-planar geometry, while the Cu(II) ion is ligated by four ammine ligands, with a distorted square planar coordination geometry. The interlinkage between Cu(I) ions and cyanide bridges produces a honeycomb-like {[Cu(2)(CN)(3)](-)}(n) anionic layer containing 18-membered planar [Cu(CN)](6) metallocycles. A [Cu(NH(3))(4)](2+) cation fills each metallocyclic cavity within pairs of exactly superimposed {[Cu(2)(CN)(3)]( )}(n) anionic layers, but there are no cations between the layers of adjacent pairs, which are offset. Pairs of N-H...N hydrogen-bonding interactions link the N-H groups of the ammine ligands to the N atoms of cyanide ligands. PMID- 22307249 TI - 1-Ferrocenylmethyl-3-(2,4,6-trimethylbenzyl)-1H-imidazolidin-3-ium iodide and trans-bis(3-benzyl-1-ferrocenylmethyl-1H-imidazolidin-2 ylidene)diiodidopalladium(II). AB - Owing to increasing interest in the use of N-heterocyclic carbenes (NHCs) based on imidazolidinium ions as ligands in the design of highly efficient transition metal-based homogeneous catalysts, the characterizations of the 1 ferrocenylmethyl-3-(2,4,6-trimethylbenzyl)imidazolidin-3-ium iodide salt, [Fe(C(5)H(5))(C(19)H(24)N(2))]I, (I), and the palladium complex trans-bis(3 benzyl-1-ferrocenylmethyl-1H-imidazolidin-2-ylidene)diiodidopalladium(II), [Fe(2)Pd(C(5)H(5))(2)(C(16)H(17)N(2))(2)I(2)], (II), are reported. Compound (I) has two iodide anions and two imidazolidinium cations within the asymmetric unit (Z' = 2). The two cations have distinctly different conformations, with the ferrocene groups orientated exo and endo with respect to the N-heterocyclic carbene. Weak C-H donor hydrogen bonds to both the iodide anions and the pi system of the mesitylene group combine to form two-dimensional layers perpendicular to the crystallographic c direction. Only one of the formally charged imidazolidinium rings forms a near-linear hydrogen bond with an iodide anion. Complex (II) shows square-planar coordination around the Pd(II) metal, which is located on an inversion centre (Z' = 0.5). The ferrocene and benzyl substituents are in a trans-anti arrangement. The Pd-C bond distance between the N-heterocyclic carbene ligands and the metal atom is 2.036 (7) A. A survey of related structures shows that the lengthening of the N-C bonds and the closure of the N-C-N angle seen here on metal complexation is typical of similar NHCs and their complexes. PMID- 22307250 TI - Molecular complexes of dimethyl sulfoxide with tri- and dichloromethane. AB - Crystals of molecular complexes of dimethyl sulfoxide with trichloromethane (chloroform), (CH(3))(2)SO.2CHCl(3), (I), and dichloromethane, (CH(3))(2)SO.CH(2)Cl(2), (II), have been grown in situ. In both compounds, the components are linked together by (Cl)C-H...O interactions. The dimethyl sulfoxide molecules in (I) are bound into chains by C-H...O interactions. In (II), pairs of the components form centrosymmetric rings, linked into a three dimensional network by C-H...O contacts and dipole-dipole interactions between dimethyl sulfoxide molecules. PMID- 22307251 TI - Clarithromycin form I determined by synchrotron X-ray powder diffraction. AB - The structure of the metastable form I polymorph of the macrolide antibiotic clarithromycin, C(38)H(69)NO(13), was determined by a powder diffraction method using synchrotron radiation. The space group of form I is P2(1)2(1)2. The initial model was determined by a molecular replacement method using the structure of clarithromycin form 0 as a search model, and the final structure was obtained through Rietveld refinements. In the form I crystal structure, the clarithromycin molecules are aligned parallel along the a axis in a head-to-tail manner with intermolecular hydrogen bonds between the hydroxy O atoms. The dimethylamine groups of the clarithromycin molecule interdigitate between neighbouring head-to tail clarithromycin alignments. The novel crystal packing found in form I provides a mechanism that describes the transformation of form 0 to form I. PMID- 22307252 TI - 2-Ammonio-5-chloro-4-methylbenzenesulfonate, its 1-methyl-2-pyrrolidone and dimethyl sulfoxide monosolvates and a corrected structure of 2,2'-(1,4 phenylene)di(4,5-dihydroimidazolium) bis(4-aminobenzenesulfonate) dihydrate. AB - 2-Ammonio-5-chloro-4-methylbenzenesulfonate, C(7)H(8)ClNO(3)S, (Ia), is an intermediate in the synthesis of lake red azo pigments. The present structure determination from single-crystal data confirms the results of a previous powder diffraction determination [Beko, Thoms, Bruning, Alig, van de Streek, Lakatos, Glaubitz & Schmidt (2010). Z. Kristallogr. 225, 382-387]. The zwitterionic tautomeric form is confirmed. During a polymorph screening, two additional pseudopolymorphs were obtained, viz. 2-ammonio-5-chloro-4-methylbenzenesulfonate 1-methyl-2-pyrrolidone monosolvate, C(7)H(8)ClNO(3)S.C(5)H(9)NO, (Ib), and 2 ammonio-5-chloro-4-methylbenzenesulfonate dimethyl sulfoxide monosolvate, C(7)H(8)ClNO(3)S.C(2)H(6)OS, (Ic). The molecules of (Ib) have crystallographic m symmetry. The 1-methyl-2-pyrrolidone solvent molecule has an envelope conformation and is disordered around the mirror plane. The structure shows hydrogen-bonded ladders of molecules [graph-set notation C(2)(2)(6)R(2)(2)(12)] in the [010] direction. The benzene groups of adjacent ladders are also stacked in this direction. A different type of hydrogen-bonded ladder [graph-set notation C(6)R(2)(2)(4)R(4)(4)(12)] occurs in (Ic). In (Ia), (Ib) and (Ic), the molecules correspond to the zwitterionic tautomer. The structure of the cocrystal of 4 aminobenzenesulfonic acid with 1,4-bis(4,5-dihydroimidazol-2-yl)benzene [Shang, Ren, Wang, Lu & Yang (2009). Acta Cryst. E65, o2221-o2222] is corrected; it actually contains 4-aminobenzenesulfonate anions and 2,2'-(1,4 phenylene)di(dihydroimidazolium) dications, i.e. 2,2'-(1,4-phenylene)di(4,5 dihydroimidazolium) bis(4-aminobenzenesulfonate) dihydrate, C(12)H(16)N(4)(2+).2C(6)H(6)NO(3)S(-).2H(2)O. Hence, all known structures of aminobenzenesulfonic acid complexes contain ionic or zwitterionic molecules; there is no known structure with a neutral aminobenzenesulfonic acid molecule. PMID- 22307253 TI - The double H-atom acceptability of the P=O group in new XP(O)(NHCH2C6H4-2-Cl)2 phosphoramidates [X = C6H5O- and CF3C(O)NH-]: a database analysis of compounds having a P(O)(NHR) group. AB - In the hydrogen-bond patterns of phenyl bis(2-chlorobenzylamido)phosphinate, C(20)H(19)Cl(2)N(2)O(2)P, (I), and N,N'-bis(2-chlorobenzyl)-N''-(2,2,2 trifluoroacetyl)phosphoric triamide, C(16)H(15)Cl(2)F(3)N(3)O(2)P, (II), the O atoms of the related phosphoryl groups act as double H-atom acceptors, so that the P=O...(H-N)(2) hydrogen bond in (I) and the P=O...(H-N(amide))(2) and C=O...H N(C(O)NHP(O)) hydrogen bonds in (II) are responsible for the aggregation of the molecules in the crystal packing. The presence of a double H-atom acceptor centre is a result of the involvement of a greater number of H-atom donor sites with a smaller number of H-atom acceptor sites in the hydrogen-bonding interactions. This article also reviews structures having a P(O)NH group, with the aim of finding similar three-centre hydrogen bonds in the packing of phosphoramidate compounds. This analysis shows that the factors affecting the preference of the above-mentioned O atom to act as a double H-atom acceptor are: (i) a higher number of H-atom donor sites relative to H-atom acceptor centres in molecules with P(=O)(NH)(3), (N)P(=O)(NH)(2), C(=O)NHP(=O)(NH)(2) and (NH)(2)P(=O)OP(=O)(NH)(2) groups, and (ii) the remarkable H-atom acceptability of this atom relative to the other acceptor centre(s) in molecules containing an OP(=O)(NH)(2) group, with the explanation that the N atom bound to the P atom in almost all of the structures found does not take part in hydrogen bonding as an acceptor. Moreover, the differences in the H-atom acceptability of the phosphoryl O atom relative to the O atom of the alkoxy or phenoxy groups in amidophosphoric acid esters may be illustrated by considering the molecular packing of compounds having (O)(2)P(=O)(NH) and (O)P(=O)(NH)(N)groups, in which the unique N-H unit in the above-mentioned molecules almost always selects the phosphoryl O atom as a partner in forming hydrogen-bond interactions. The P atoms in (I) and (II) are in tetrahedral coordination environments, and the phosphoryl and carbonyl groups in (II) are anti with respect to each other (the P and C groups are separated by one N atom). In the crystal structures of (I) and (II), adjacent molecules are linked via the above-mentioned hydrogen bonds into a linear arrangement parallel to [100] in both cases, in (I) by forming R(2)(2)(8) rings and in (II) through a combination of R(2)(2)(10) and R(2)(1)(6) rings. PMID- 22307254 TI - Anilinium dihydrogen phosphate. AB - The triclinic structure of the title compound, C(6)H(8)N(+).H(2)PO(4)(-), with three symmetry-independent structural units (Z' = 3), is formed of separate organic and inorganic layers alternating along the b axis. The building blocks of the inorganic layer are deformed H(2)PO(4) tetrahedra assembled into infinite ladders by short and hence strong hydrogen bonds. The anilinium cations forming the organic layer are not hydrogen bonded to one another, but they are anchored by four N-H...O crosslinks between the dihydrogen phosphate chains of adjacent ladders. Two H atoms of each -NH(3) group then form one normal and one bifurcated N-H...O hydrogen bond to the P=O oxygens of two tetrahedra of one chain, while the third H atom is hydrogen bonded to the nearest O atom of an adjacent chain belonging to another dihydrogen phosphate ladder. PMID- 22307255 TI - The acid adducts hydrazinium 2-hydroxybenzoate-2-hydroxybenzoic acid (1/1) and hydrazinium 3-hydroxy-2-naphthoate-3-hydroxy-2-naphthoic acid (1/1). AB - The title molecular salts, N(2)H(5)(+).C(7)H(5)O(3)(-).C(7)H(6)O(3) and N(2)H(5)(+).C(11)H(7)O(3)(-).C(11)H(8)O(3), are acid adducts containing a hydrazinium cation, one molecule of a deprotonated acid and one molecule of a neutral acid. The two compounds contain essentially identical hydrogen-bond networks between the hydrazinium cation and the acid molecules, which define closely comparable two-dimensional layers in the structures. The planes of the aromatic rings within both structures are approximately parallel and the layers are stacked with comparable intermolecular interactions. PMID- 22307256 TI - Two polymorphs and the diethylammonium salt of the barbiturate eldoral. AB - Polymorph (Ia) of eldoral [5-ethyl-5-(piperidin-1-yl)barbituric acid or 5-ethyl-5 (piperidin-1-yl)-1,3-diazinane-2,4,6-trione], C(11)H(17)N(3)O(3), displays a hydrogen-bonded layer structure parallel to (100). The piperidine N atom and the barbiturate carbonyl group in the 2-position are utilized in N-H...N and N H...O=C hydrogen bonds, respectively. The structure of polymorph (Ib) contains pseudosymmetry elements. The two independent molecules of (Ib) are connected via N-H...O=C(4/6-position) and N-H...N(piperidine) hydrogen bonds to give a chain structure in the [100] direction. The hydrogen-bonded layers, parallel to (010), formed in the salt diethylammonium 5-ethyl-5-(piperidin-1-yl)barbiturate [or diethylammonium 5-ethyl-2,4,6-trioxo-5-(piperidin-1-yl)-1,3-diazinan-1-ide], C(4)H(12)N(+).C(11)H(16)N(3)O(3)(-), (II), closely resemble the corresponding hydrogen-bonded structure in polymorph (Ia). Like many other 5,5-disubstituted derivatives of barbituric acid, polymorphs (Ia) and (Ib) contain the R(2)(2)(8) N H...O=C hydrogen-bond motif. However, the overall hydrogen-bonded chain and layer structures of (Ia) and (Ib) are unique because of the involvement of the hydrogen bond acceptor function in the piperidine group. PMID- 22307257 TI - Two polymorphs of bis(2-carbamoylguanidinium) fluorophosphonate dihydrate. AB - Two polymorphs of bis(2-carbamoylguanidinium) fluorophosphonate dihydrate, 2C(2)H(7)N(4)O(+).FO(3)P(2-).2H(2)O, are presented. Polymorph (I), crystallizing in the space group Pnma, is slightly less densely packed than polymorph (II), which crystallizes in Pbca. In (I), the fluorophosphonate anion is situated on a crystallographic mirror plane and the O atom of the water molecule is disordered over two positions, in contrast with its H atoms. The hydrogen-bond patterns in both polymorphs share similar features. There are O-H...O and N-H...O hydrogen bonds in both structures. The water molecules donate their H atoms to the O atoms of the fluorophosphonates exclusively. The water molecules and the fluorophosphonates participate in the formation of R(4)(4)(10) graph-set motifs. These motifs extend along the a axis in each structure. The water molecules are also acceptors of either one [in (I) and (II)] or two [in (II)] N-H...O hydrogen bonds. The water molecules are significant building elements in the formation of a three-dimensional hydrogen-bond network in both structures. Despite these similarities, there are substantial differences between the hydrogen-bond networks of (I) and (II). The N-H...O and O-H...O hydrogen bonds in (I) are stronger and weaker, respectively, than those in (II). Moreover, in (I), the shortest N-H...O hydrogen bonds are shorter than the shortest O-H...O hydrogen bonds, which is an unusual feature. The properties of the hydrogen-bond network in (II) can be related to an unusually long P-O bond length for an unhydrogenated fluorophosphonate anion that is present in this structure. In both structures, the N-H...F interactions are far weaker than the N-H...O hydrogen bonds. It follows from the structure analysis that (II) seems to be thermodynamically more stable than (I). PMID- 22307258 TI - Mixed crystals of 2-carbamoylguanidinium with hydrogen fluorophosphonate and hydrogen phosphite in the ratios 1:0, 0.76 (2):0.24 (2) and 0.115 (7):0.885 (7). AB - The title compounds, 2-carbamoylguanidinium hydrogen fluorophosphonate, C(2)H(7)N(4)O(+).HFO(3)P(-), (I), 2-carbamoylguanidinium-hydrogen fluorophosphonate-hydrogen phosphite (1/0.76/0.24), C(2)H(7)N(4)O(+).0.76HFO(3)P( ).0.24H(2)O(3)P(-), (II), and 2-carbamoylguanidinium-hydrogen fluorophosphonate hydrogen phosphite (1/0.115/0.885), C(2)H(7)N(4)O(+).0.115HFO(3)P( ).0.885H(2)O(3)P(-), (III), are isostructural with guanylurea hydrogen phosphite, C(2)H(7)N(4)O(+).H(2)O(3)P(-) [Fridrichova, Nemec, Cisarova & Nemec (2010). CrystEngComm, 12, 2054-2056]. They constitute structures where the hydrogen phosphite anion has been fully or partially replaced by hydrogen fluorophosphonate. The title structures are the fourth example of isostructural compounds which differ by the presence of hydrogen fluorophosphonate and hydrogen phosphite or fluorophosphonate and phosphite anions. Moreover, the present study reports structures with these mixed anions for the first time. In the reported mixed salts, the P and O atoms of either anion overlap almost exactly, as can be judged by comparison of their equivalent isotropic displacement parameters, while the P-F and P-H directions are almost parallel. There are strong O-H...O hydrogen bonds between the anions, as well as strong N-H...O hydrogen bonds between the 2 carbamoylguanidinium cations in the title structures. Altogether they form a three-dimensional hydrogen-bond pattern. Interestingly, rare N-H...F interactions are also present in the title structures. Another exceptional feature concerns the P-O(H) distances, which are about as long as the P-F distance. The dependence of P-F distances on the longest P-O distances in FO(3)P(2-) or HFO(3)P(-) is presented. The greater content of hydrogen phosphite in the mixed crystals causes a larger deformation of the cations from planarity. PMID- 22307259 TI - 4-Pyridone-terephthalic acid-water (2/1/2) and bis(3-hydroxypyridinium) terephthalate. AB - 4-Hydroxypyridine and terephthalic acid cocrystallize as a hydrate, 4-pyridone terephthalic acid-water (2/1/2), 2C(5)H(5)NO.C(8)H(6)O(4).2H(2)O, from a methanol water solution. The molecules form a two-dimensional hydrogen-bonded network resulting in sheets of hydrogen-bonded molecules that lie parallel to the (10-2) plane. In contrast, 3-hydroxypyridine and terephthalic acid form the salt bis(3 hydroxypyridinium) terephthalate, 2C(5)H(6)NO(+).C(8)H(4)O(4)(2-), giving rise to two-dimensional hydrogen-bonded sheets extending through the lattice parallel to the (102) plane. PMID- 22307260 TI - 4-Carboxypiperidinium 1-carboxycyclobutane-1-carboxylate. AB - The title salt, C(6)H(12)NO(2)(+).C(6)H(7)O(4)(-) or ISO(+).CBDC(-), is an ionic ensemble assisted by hydrogen bonds. The amino acid moiety (ISO or piperidine-4 carboxylic acid) has a protonated ring N atom (ISO(+) or 4-carboxypiperidinium), while the semi-protonated acid (CBDC(-) or 1-carboxycyclobutane-1-carboxylate) has the negative charge residing on one carboxylate group, leaving the other as a neutral -COOH group. The -(+)NH(2)- state of protonation allows the formation of a two-dimensional crystal packing consisting of zigzag layers stacked along a separated by van der Waals distances. The layers extend in the bc plane connected by a complex network of N-H...O and O-H...O hydrogen bonds. Wave-like ribbons, constructed from ISO(+) and CBDC(-) units and described by the graph-set symbols C(3)(3)(10) and R(3)(3)(14), run alternately in opposite directions along c. Intercalated between the ribbons are ISO(+) cations linked by hydrogen bonds, forming rings described by the graph-set symbols R(6)(6)(30) and R(4)(2)(18). A detailed analysis of the structures of the individual components and the intricate hydrogen-bond network of the crystal structure is given. PMID- 22307261 TI - Conformational studies of hydantoin-5-acetic acid and orotic acid. AB - Hydantoin-5-acetic acid [2-(2,5-dioxoimidazolidin-4-yl)acetic acid] and orotic acid (2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid) each contain one rigid acceptor-donor-acceptor hydrogen-bonding site and a flexible side chain, which can adopt different conformations. Since both compounds may be used as coformers for supramolecular complexes, they have been crystallized in order to examine their conformational preferences, giving solvent-free hydantoin-5-acetic acid, C(5)H(6)N(2)O(4), (I), and three crystals containing orotic acid, namely, orotic acid dimethyl sulfoxide monosolvate, C(5)H(4)N(2)O(4).C(2)H(6)OS, (IIa), dimethylammonium orotate-orotic acid (1/1), C(2)H(8)N(+).C(5)H(3)N(2)O(4)( ).C(5)H(4)N(2)O(4), (IIb), and dimethylammonium orotate-orotic acid (3/1), 3C(2)H(8)N(+).3C(5)H(3)N(2)O(4)(-).C(5)H(4)N(2)O(4), (IIc). The crystal structure of (I) shows a three-dimensional network, with the acid function located perpendicular to the ring. Interestingly, the hydroxy O atom acts as an acceptor, even though the carbonyl O atom is not involved in any hydrogen bonds. However, in (IIa), (IIb) and (IIc), the acid functions are only slightly twisted out of the ring planes. All H atoms of the acidic functions are directed away from the rings and, with respect to the carbonyl O atoms, they show an antiperiplanar conformation in (I) and synperiplanar conformations in (IIa), (IIb) and (IIc). Furthermore, in (IIa), (IIb) and (IIc), different conformations of the acid O=C-C N torsion angle are observed, leading to different hydrogen-bonding arrangements depending on their conformation and composition. PMID- 22307262 TI - Stability effects on results of diffusion tensor imaging analysis by reduction of the number of gradient directions due to motion artifacts: an application to presymptomatic Huntington's disease. AB - In diffusion tensor imaging (DTI), an improvement in the signal-to-noise ratio (SNR) of the fractional anisotropy (FA) maps can be obtained when the number of recorded gradient directions (GD) is increased. Vice versa, elimination of motion corrupted or noisy GD leads to a more accurate characterization of the diffusion tensor. We previously suggest a slice-wise method for artifact detection in FA maps. This current study applies this approach to a cohort of 18 premanifest Huntington's disease (pHD) subjects and 23 controls. By 2-D voxelwise statistical comparison of original FA-maps and FA-maps with a reduced number of GD, the effect of eliminating GD that were affected by motion was demonstrated.We present an evaluation metric that allows to test if the computed FA-maps (with a reduced number of GD) still reflect a "true" FA-map, as defined by simulations in the control sample. Furthermore, we investigated if omitting data volumes affected by motion in the pHD cohort could lead to an increased SNR in the resulting FA maps.A high agreement between original FA maps (with all GD) and corrected FA maps (i.e. without GD corrupted by motion) were observed even for numbers of eliminated GD up to 13. Even in one data set in which 46 GD had to be eliminated, the results showed a moderate agreement. PMID- 22307263 TI - The effect of different interfaces and confinement on the structure of the ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide entrapped in cationic and anionic reverse micelles. AB - The behavior of the ionic liquid (IL) 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([bmim][Tf(2)N]) entrapped in two reverse micelles (RMs) formed in an aromatic solvent as dispersant pseudophase: [bmim][Tf(2)N]/benzyl-n-hexadecyldimethylammonium chloride (BHDC)/chlorobenzene and [bmim][Tf(2)N]/sodium 1,4-bis-2-ethylhexylsulfosuccinate (AOT)/chlorobenzene, was investigated using dynamic light scattering (DLS), FT-IR and (1)H NMR spectroscopies. DLS results reveal the formation of RMs containing [bmim][Tf(2)N] as a polar component since the droplet size values increase as the W(s) (W(s) = [[bmim][Tf(2)N]]/[surfactant]) increases. Furthermore, it shows that the RMs consist of discrete spherical and non-interacting droplets of [bmim][Tf(2)N] stabilized by the surfactants. Important differences in the structure of [bmim][Tf(2)N] entrapped inside BHDC RMs, in comparison with the neat IL, are observed from the FT-IR and (1)H NMR measurements. The electrostatic interactions between anions and cations from [bmim][Tf(2)N] and BHDC determine the solvent structure encapsulated inside the nano-droplets. It seems that the IL structure is disrupted due to the electrostatic interaction between the [Tf(2)N](-) and the cationic BHDC polar head (BHD(+)) giving a high ion pair degree between BHD(+) and [Tf(2)N](-) at a low IL content. On the other hand, for the AOT RMs there is no evidence of strong IL-surfactant interaction. The electrostatic interaction between the SO(3)(-) group and the Na(+) counterion in AOT seems to be stronger than the possible [bmim](+)-SO(3)(-) interaction at the interface. Thus, the structure of [bmim][Tf(2)N] encapsulated is not particularly disrupted by the anionic surfactant at all W(s) studied, in contrast to the BHDC RM results. Nevertheless, there is evidence of confinement in the AOT RMs because the [bmim](+)-[Tf(2)N](-) interaction is stronger than in bulk solution. Thus, the IL is more associated upon confinement. Our results reveal that the [bmim][Tf(2)N] structure can be modified in a different manner inside RMs by varying the kind of surfactant used to create the RMs and the IL content (W(s)). These facts can be very important if these media are used as nanoreactors because unique microenvironments can be easily created by simply changing the RM components and W(s). PMID- 22307264 TI - Chemopreventive efficacy of Targretin in rodent models of urinary bladder, colon/intestine, head and neck and mammary cancers. AB - The chemopreventive efficacy of Targretin was evaluated in various rodent cancer models. In the rat model of 4-hydroxybutyl(butyl)nitrosamine (OH-BBN)-induced urinary bladder cancer, it was found that Targretin administered in the diet (beginning one week after the last OH-BBN treatment) for 5.5 months increased the number and size of urinary bladder cancers. In the azoxymethane (AOM)-induced model of colon carcinogenesis (in which rats develop minimally invasive colonic cancers), Targretin was ineffective as a chemopreventive agent, decreasing neither tumor incidence nor multiplicity. Treatment of Min mice with Targretin for 45 days similarly failed to decrease the multiplicity of small intestinal tumors. Similarly, no preventive efficacy was noted for Targretin when the incidence of tumors in the head and neck model (squamous cell tongue tumors) induced by 4-nitroquinoline 1-oxide (4-NQO) were examined. In contrast, use of even a suboptimal dose of Targretin (40 ppm) in a sensitive breast cancer model [methylnitrosourea (MNU)-induced ER+ mammary cancers] reduced cancer multiplicity by 60%. Finally, based on the hypothesis that Targretin may decrease the expression of COX-2, the effects of Targretin and COX inhibitors were compared in these models. There was minimal overlap of efficacy. That is, models which were relatively susceptible to NSAIDs or COX-2 inhibitors tended not to be sensitive to Targretin and vice versa. PMID- 22307266 TI - Efficacy of zoledronic acid in postmenopausal Japanese women with early breast cancer receiving adjuvant letrozole: 12-month results. AB - Aromatase inhibitor-associated bone loss has not been proved in the Japanese or Asian women. The aim of this study was to evaluate an upfront or delayed strategy of bone protection therapy with zoledronic acid administered at 4 mg every 6 months in postmenopausal Japanese women with early breast cancer to compare with results of the Z-FAST and ZO-FAST studies in western countries. Postmenopausal women with hormone receptor positive early breast cancer receiving adjuvant letrozole were randomly assigned to receive either upfront or delayed-start zoledronic acid (4 mg intravenously every 6 months). The delayed group received zoledronic acid when lumbar spine (L(2)-L(4)) bone mineral density (BMD) decreased to less than young adult mean -2.0SD or when a nontraumatic fracture occurred. The primary endpoint of this study was to compare the percent change in L(1)-L(4) BMD at 12 months between the groups. Secondary endpoints included percent changes in L(2)-L(4) and total hip (TH) BMD. The upfront and delayed groups included 94 and 95 patients, respectively. At 12 months, L(1)-L(4), L(2) L(4), and TH BMD significantly decreased by 2.0, 2.4, and 2.4%, respectively, in the delayed group. L(1)-L(4) BMD was 4.9% higher in the upfront group than in the delayed group (95% CI 3.9-5.8%; p < 0.001). L(2)-L(4) BMD was 5.6% higher (95% CI 4.5-6.6%; p < 0.001), and TH BMD was 4.4% higher (95% CI 3.3-5.4%; p < 0.001). At 12 months, upfront zoledronic acid therapy prevented bone loss in postmenopausal Japanese women who were receiving adjuvant letrozole, confirming the Z-/ZO-FAST study results in western populations. PMID- 22307267 TI - Recommendations for the aesthetic evaluation of breast cancer conservative treatment. AB - During the Turning Subjective Into Objective seminar held in Lisbon in May 2011, experts in the topic gathered to discuss the unsolved problems of aesthetic evaluation of breast-conserving treatment (BCT). The purpose of this study is to review the main methodological issues related to the aesthetic evaluation of BCT, to discuss currently used methods of evaluation and the lack of a gold standard, and to write a set of recommendations that can be used as guidance for the aesthetic evaluation of BCT. PMID- 22307268 TI - Ni2+/surfactant-assisted route to porous alpha-Fe2O3 nanoarchitectures. AB - Uniform porous three-dimensional nanoarchitectures of alpha-Fe(2)O(3) with high yield have been synthesized by a route based on a Ni(2+)/surfactant system. The obtained alpha-Fe(2)O(3) has a flue-like porous morphology with a rough surface. What is more, spatially ordered nodes and meshes are presented in these networks. By adjusting the experimental parameters such as temperature, reaction time, proportion of Ni(2+)/PVP and types of cation, we can control the morphology of the samples well. A possible formation mechanism is proposed to explain the growth of the flue-like nanostructures. The obtained flue-like porous alpha Fe(2)O(3) has a large specific surface area of 88.82 m(2) g(-1). It exhibits significantly enhanced visible-light-driven photocatalytic performance in the degradation of methylene blue, compared with alpha-Fe(2)O(3) nanoparticles. This work not only enriches the synthesis methods of porous architectures, but also facilitates the applications of alpha-Fe(2)O(3) in the fields of water treatment, sunlight utilization and so forth. PMID- 22307269 TI - GNAQ and GNA11 mutations in melanocytomas of the central nervous system. PMID- 22307270 TI - Unusual electronic structure of bis-isocyanide complexes of iron(III) porphyrinoids. AB - A series of isocyanide complexes, [Fe(Porphyrinoid)((t)BuNC)(2)](+), were synthesized and examined for their physicochemical properties. The molecular structure of the bis((t)BuNC) adduct of the iron(III) porphycene (1) and corrphycene (2) adopting the (d(xy))(2)(d(xz), d(yz))(3) ground state were determined for the first time. Furthermore, 1 and 2 showed unusual crossover phenomena between different electron configurations, (d(xy))(2)(d(xz), d(yz))(3) ground state and (d(xz), d(yz))(4)(d(xy))(1) ground state, by the addition of the external stimuli. PMID- 22307271 TI - Evaluation of stent visibility by flat panel detector CT in patients treated for intracranial aneurysms. AB - INTRODUCTION: This study aimed to evaluate the visibility of stents using high resolution computed tomography (CT) acquisitions acquired with flat panel detector (XperCT, Allura series, Philips Healthcare, The Netherlands) for endovascular treatment of intracranial aneurysms. METHODS: On a 24-month period, 48 patients endovascularly treated by coiling and stenting (59 stents) for intracranial aneurysms were explored by flat panel detector CT technique. A sequence of 620 2D images was acquired over an angle of 240 degrees using a 1,024 * 1,024 pixel matrix detector within a 48-cm field of view. The images were retrospectively analyzed independently by two neuroradiologists. Evaluation criteria were percentage of visualization of the stents and stent deployment (kinking or unsatisfactory deployment of the stent). RESULTS: Evaluation of the stent was feasible for all the patients. Stent visibility by XperCT was overall estimated at 76% of the stent length. Difficulties to analyze the stents were related to coil artifacts but not to packing density or aneurysm location. Stent length visualization was higher when the acquisition was performed before additional coiling (P < 0.0001). Mild kinking/misdeployment was noticed in 22% of the cases. CONCLUSION: XperCT technique provides multiplanar and 3D reconstructions that allows for a satisfying visualization of intracranial stents. This CT-like acquisition should be performed after the stent deployment and before coiling, in order to obtain better stent visualization. PMID- 22307272 TI - Salivary duct carcinomas: clinical and CT and MR imaging features in 20 patients. AB - INTRODUCTION: Salivary duct carcinoma (SDC) is an uncommon high grade adenocarcinoma of the salivary gland with a grave prognosis. The aim of this study was to investigate the clinical and CT and MR imaging features of SDC. METHODS: We retrospectively evaluated the clinical and CT and MR imaging findings in 20 patients (14 men and six women; mean age, 59 years) with histologically proved SDC. We also tried to correlate clinicoradiological tumor staging with pathologic tumor staging in 17 patients who underwent surgery. RESULTS: The tumor originated in the parotid gland (n = 11; 55%), the submandibular gland (n = 7; 35%) and the buccal space along the distal Stensen's duct (n = 2; 10%). Locoregional recurrence occurred in 41% and distant metastasis in 47%. Fifty eight percent died of the disease with a mean survival period of 32 months after diagnosis. On CT and MR images, SDC was mostly seen as an ill-defined (85%) and infiltrative (60%) mass with frequent calcification (50%) and necrosis (80%). Although various signal intensities were seen on MR images, six of nine tumors contained the areas of marked hypointensity on T2-weighted images. Clinicoradiological tumor staging correlated well with pathologic tumor staging in 82% of the patients. CONCLUSION: Ill-defined, infiltrative mass with calcification on CT scans and the areas of marked hypointensity on T2-weighted MR images may be useful radiologic features to suggest the diagnosis of SDC. CT and MR imaging are useful for staging of SDC. PMID- 22307273 TI - MicroRNA profiling in murine liver after partial hepatectomy. AB - Liver is uniquely capable to repair itself after injury. Multiple molecular and biochemical processes initiated after partial hepatectomy, lead to proliferation of all cells within the liver. MicroRNAs (miRNAs) are a class of highly abundant non-coding RNA molecules that cause post-transcriptional gene repression and are involved in several biological processes including cell cycle regulation and differentiation. In this study, we examined the expression levels of miRNAs in liver tissue received from control mice (L0) and compared them with the corresponding levels in liver tissue 12 h after liver regeneration induced by 2/3 partial hepatectomy (L12). MiRNA expression was investigated using microRNA profiling. Further qPCR analysis was used for validation of the differentially expressed miRNAs at an early stage of liver regeneration, induced by 2/3 partial hepatectomy. TargetScan and Gene Ontology (GO) analyses were performed in order to identify the possible miRNA target genes and their ontology, respectively. A subset of miRNAs was found to be differentially expressed during liver regeneration. Mmu-miR-21 and mmu-miR-30b* showed the higher levels of up regulation in liver tissue from the hepatectomized mice at the end of the experiment (L12) compared to the sham operated mice (L0). Mmu-miR-21 up regulation was further confirmed by qPCR. In situ hybridization (ISH) revealed that mmu-miR-21 exhibited the higher levels of expression at 12 h post hepatectomy. On the contrary, mmu-miR-34c*, mmu-miR-144, mmu-miR-207, mmu-miR 207, mmu-miR-451, mmu-miR-582-3p and mmu-miR-290-5p exhibited <0.5 down regulation in liver tissue after partial hepatectomy in L12 vs. L0 mice. The results from microarray and qPCR analyses were in good agreement. In conclusion, our results provide important information regarding the differentially expressed miRNAs in murine liver tissue before and after partial hepatectomy. The early up regulation of mmu-miR-21 during the process of liver regeneration suggests a regulatory role in liver regeneration in vivo. PMID- 22307274 TI - Structural basis for recognition of H3K56-acetylated histone H3-H4 by the chaperone Rtt106. AB - Dynamic variations in the structure of chromatin influence virtually all DNA related processes in eukaryotes and are controlled in part by post-translational modifications of histones. One such modification, the acetylation of lysine 56 (H3K56ac) in the amino-terminal alpha-helix (alphaN) of histone H3, has been implicated in the regulation of nucleosome assembly during DNA replication and repair, and nucleosome disassembly during gene transcription. In Saccharomyces cerevisiae, the histone chaperone Rtt106 contributes to the deposition of newly synthesized H3K56ac-carrying H3-H4 complex on replicating DNA, but it is unclear how Rtt106 binds H3-H4 and specifically recognizes H3K56ac as there is no apparent acetylated lysine reader domain in Rtt106. Here, we show that two domains of Rtt106 are involved in a combinatorial recognition of H3-H4. An N terminal domain homodimerizes and interacts with H3-H4 independently of acetylation while a double pleckstrin-homology (PH) domain binds the K56 containing region of H3. Affinity is markedly enhanced upon acetylation of K56, an effect that is probably due to increased conformational entropy of the alphaN helix of H3. Our data support a mode of interaction where the N-terminal homodimeric domain of Rtt106 intercalates between the two H3-H4 components of the (H3-H4)(2) tetramer while two double PH domains in the Rtt106 dimer interact with each of the two H3K56ac sites in (H3-H4)(2). We show that the Rtt106-(H3-H4)(2) interaction is important for gene silencing and the DNA damage response. PMID- 22307275 TI - Brassinosteroid regulates stomatal development by GSK3-mediated inhibition of a MAPK pathway. AB - Plants must coordinate the regulation of biochemistry and anatomy to optimize photosynthesis and water-use efficiency. The formation of stomata, epidermal pores that facilitate gas exchange, is highly coordinated with other aspects of photosynthetic development. The signalling pathways controlling stomata development are not fully understood, although mitogen-activated protein kinase (MAPK) signalling is known to have key roles. Here we demonstrate in Arabidopsis that brassinosteroid regulates stomatal development by activating the MAPK kinase kinase (MAPKKK) YDA (also known as YODA). Genetic analyses indicate that receptor kinase-mediated brassinosteroid signalling inhibits stomatal development through the glycogen synthase kinase 3 (GSK3)-like kinase BIN2, and BIN2 acts upstream of YDA but downstream of the ERECTA family of receptor kinases. Complementary in vitro and in vivo assays show that BIN2 phosphorylates YDA to inhibit YDA phosphorylation of its substrate MKK4, and that activities of downstream MAPKs are reduced in brassinosteroid-deficient mutants but increased by treatment with either brassinosteroid or GSK3-kinase inhibitor. Our results indicate that brassinosteroid inhibits stomatal development by alleviating GSK3-mediated inhibition of this MAPK module, providing two key links; that of a plant MAPKKK to its upstream regulators and of brassinosteroid to a specific developmental output. PMID- 22307277 TI - "Click"-modification of a functionalized poly(3,4-ethylenedioxythiophene) (PEDOT) soluble in organic solvents. AB - A PEDOT-based conductive copolymer soluble in organic solvents was synthesized electrochemically using dihexyl-EDOT and azidomethyl-EDOT as monomers and was successfully post-functionalized by "click"-cycloaddition reaction with a functionalized terminal alkyne under mild heterogeneous conditions. PMID- 22307276 TI - DNase I sensitivity QTLs are a major determinant of human expression variation. AB - The mapping of expression quantitative trait loci (eQTLs) has emerged as an important tool for linking genetic variation to changes in gene regulation. However, it remains difficult to identify the causal variants underlying eQTLs, and little is known about the regulatory mechanisms by which they act. Here we show that genetic variants that modify chromatin accessibility and transcription factor binding are a major mechanism through which genetic variation leads to gene expression differences among humans. We used DNase I sequencing to measure chromatin accessibility in 70 Yoruba lymphoblastoid cell lines, for which genome wide genotypes and estimates of gene expression levels are also available. We obtained a total of 2.7 billion uniquely mapped DNase I-sequencing (DNase-seq) reads, which allowed us to produce genome-wide maps of chromatin accessibility for each individual. We identified 8,902 locations at which the DNase-seq read depth correlated significantly with genotype at a nearby single nucleotide polymorphism or insertion/deletion (false discovery rate = 10%). We call such variants 'DNase I sensitivity quantitative trait loci' (dsQTLs). We found that dsQTLs are strongly enriched within inferred transcription factor binding sites and are frequently associated with allele-specific changes in transcription factor binding. A substantial fraction (16%) of dsQTLs are also associated with variation in the expression levels of nearby genes (that is, these loci are also classified as eQTLs). Conversely, we estimate that as many as 55% of eQTL single nucleotide polymorphisms are also dsQTLs. Our observations indicate that dsQTLs are highly abundant in the human genome and are likely to be important contributors to phenotypic variation. PMID- 22307278 TI - The use of human milk and breastfeeding in the neonatal intensive care unit: NANN position statement #3052. PMID- 22307279 TI - Modulation of function in a minimalist heme-binding membrane protein. AB - De novo designed heme-binding proteins have been used successfully to recapitulate features of natural hemoproteins. This approach has now been extended to membrane-soluble model proteins. Our group designed a functional hemoprotein, ME1, by engineering a bishistidine binding site into a natural membrane protein, glycophorin A (Cordova et al. in J Am Chem Soc 129:512-518, 2007). ME1 binds iron(III) protoporphyrin IX with submicromolar affinity, has a redox potential of -128 mV, and displays peroxidase activity. Here, we show the effect of aromatic residues in modulating the redox potential in the context of a membrane-soluble model system. We designed aromatic interactions with the heme through a single-point mutant, G25F, in which a phenylalanine is designed to dock against the porphyrin ring. This mutation results in roughly tenfold tighter binding to iron(III) protoporphyrin IX (K(d,app) = 6.5 * 10(-8) M), and lowers the redox potential of the cofactor to -172 mV. This work demonstrates that specific design features aimed at controlling the properties of bound cofactors can be introduced in a minimalist membrane hemoprotein model. The ability to modulate the redox potential of cofactors embedded in artificial membrane proteins is crucial for the design of electron transfer chains across membranes in functional photosynthetic devices. PMID- 22307280 TI - Potential biodiversity benefits from international programs to reduce carbon emissions from deforestation. AB - Deforestation is the second largest anthropogenic source of carbon dioxide emissions and options for its reduction are integral to climate policy. In addition to providing potentially low cost and near-term options for reducing global carbon emissions, reducing deforestation also could support biodiversity conservation. However, current understanding of the potential benefits to biodiversity from forest carbon offset programs is limited. We compile spatial data on global forest carbon, biodiversity, deforestation rates, and the opportunity cost of land to examine biodiversity conservation benefits from an international program to reduce carbon emissions from deforestation. Our results indicate limited geographic overlap between the least-cost areas for retaining forest carbon and protecting biodiversity. Therefore, carbon-focused policies will likely generate substantially lower benefits to biodiversity than a more biodiversity-focused policy could achieve. These results highlight the need to systematically consider co-benefits, such as biodiversity in the design and implementation of forest conservation programs to support international climate policy. PMID- 22307281 TI - Aphysiologic performance on dynamic posturography in work-related patients. AB - It has been suggested that malingering should be suspected in patients suffering from dizziness or imbalance and who had a potential gain associated with insurance and worker's compensation claims. This study aimed to assess and compare the prevalence of aphysiologic performance on computerized dynamic posturography (CDP) in patients with the potential for secondary gain using a retrospective review of two groups of patients: work-related patients referred for dizziness and/or imbalance (Group 1) were compared against a group of patients with complaints of dizziness or imbalance, who had no history of work related injury, or litigation procedures (Group 2). CDP and videonystagmography (VNG) were carried out in all patients. The Sensory Organization Test summaries were scored as normal, aphysiologic, or vestibular using the scoring method published by Cevette et al. in Otolaryngol Head Neck Surg 112:676-688 (1995). 24 out of 88 (27%) patients had aphysiologic CDP in Group 1 and 9 out of 51 (18%) in Group 2 but these differences were not significant (p > 0.05). Definite signs of vestibular dysfunction were found in 12 out of 24 (50%) of patients with aphysiologic performance in Group 1 although the presence of VNG abnormalities was significantly higher (p = 0.005) in Group 2. The hypothesis that the occupational group could show a significantly higher rate of aphysiologic results than a control group is not confirmed. Furthermore, VNG abnormalities were found in 50% of the work-related cases with non organic sway patterns. These results suggest that patient's complaints should be considered genuine in work-related cases and due caution exercised when evaluating aphysiologic CDP patterns. PMID- 22307282 TI - Temperature-dependent production of various PlcR-controlled virulence factors in Bacillus weihenstephanensis strain KBAB4. AB - The Bacillus cereus sensu lato complex has recently been divided into several phylogenetic groups with clear differences in growth temperature range. However, only a few studies have investigated the actual pathogenic potential of the psychrotolerant strains of the B. cereus group at low temperature, and little information is available concerning gene expression at low temperature. We found that vegetative cells of the psychrotolerant B. weihenstephanensis strain KBAB4 were pathogenic against the model insect Galleria mellonella at 15 degrees C but not at 30 degrees C. A similar temperature-dependent difference also was observed for the supernatant, which was cytotoxic to Vero epithelial cell lines and to murine macrophage J774 cells at 15 degrees C but not at 30 degrees C. We therefore determined the effect of low temperature on the production of various proteins putatively involved in virulence using two-dimensional protein gel electrophoresis, and we showed that the production of the Hbl enterotoxin and of two proteases, NprB and NprP2, was greater at a growth temperature of 15 degrees C than at 30 degrees C. The quantification of the mRNA levels for these virulence genes by real-time quantitative PCR at both temperatures showed that there was also more mRNA present at 15 degrees C than at 30 degrees C. We also found that at 15 degrees C, hbl mRNA levels were maximal in the mid- to late exponential growth phase. In conclusion, we found that the higher virulence of the B. cereus KBAB4 strain at low temperature was accompanied by higher levels of the production of various known PlcR-controlled virulence factors and by a higher transcriptional activity of the corresponding genes. PMID- 22307283 TI - Polyphasic screening, homopolysaccharide composition, and viscoelastic behavior of wheat Sourdough from a Leuconostoc lactis and Lactobacillus curvatus exopolysaccharide-producing starter culture. AB - After isolation from different doughs and sourdoughs, 177 strains of lactic acid bacteria were screened at the phenotypic level for exopolysaccharide production on media containing different carbohydrate sources. Two exopolysaccharide producing lactic acid bacteria (Lactobacillus curvatus 69B2 and Leuconostoc lactis 95A) were selected through quantitative analysis on solid media containing sucrose and yeast extract. The PCR detection of homopolysaccharide (gtf and lev) and heteropolysaccharide (epsA, epsB, epsD and epsE, and epsEFG) genes showed different distributions within species and strains of the lactic acid bacteria studied. Moreover, in some strains both homopolysaccharide and heteropolysaccharide genes were detected. Proton nuclear magnetic resonance spectra suggest that Lactobacillus curvatus 69B2 and Leuconostoc lactis 95A produced the same exopolysaccharide, which was constituted by a single repeating glucopyranosyl unit linked by an alpha-(1->6) glycosidic bond in a dextran-type carbohydrate. Microbial growth, acidification, and viscoelastic properties of sourdoughs obtained by exopolysaccharide-producing and nonproducing lactic acid bacterial strains were evaluated. Sourdough obtained after 15 h at 30 degrees C with exopolysaccharide-producing lactic acid bacteria reached higher total titratable acidity as well as elastic and dissipative modulus curves with respect to the starter not producing exopolysaccharide, but they showed similar levels of pH and microbial growth. On increasing the fermentation time, no difference in the viscoelastic properties of exopolysaccharide-producing and nonproducing samples was observed. This study suggests that dextran-producing Leuconostoc lactis 95A and Lactobacillus curvatus 69B2 can be employed to prepare sourdough, and this would be particularly useful to improve the quality of baked goods while avoiding the use of commercially available hydrocolloids as texturizing additives. PMID- 22307284 TI - Identification of a pheA gene associated with Streptococcus mitis by using suppression subtractive hybridization. AB - We performed suppression subtractive hybridization to identify genomic differences between Streptococcus mitis and Streptococcus pneumoniae. Based on the pheA gene, a primer set specific to S. mitis detection was found in 18 out of 103 S. mitis-specific clones. Our findings would be useful for discrimination of S. mitis from other closely related cocci in the oral environment. PMID- 22307285 TI - Functional assignment of YvgO, a novel set of purified and chemically characterized proteinaceous antifungal variants produced by Bacillus thuringiensis SF361. AB - This study reports a novel class of antifungal protein derived from bacterial origin. Bacillus thuringiensis SF361, the strain also responsible for producing the novel bacteriocin thurincin H, exhibits broad antifungal activity against select members of several fungal genera, including Aspergillus, Byssochlamys, and Penicillium, as well as the pathogenic yeast Candida albicans. Optimal antifungal production and secretion were observed after-log phase growth when incubated at 37 degrees C in a carbohydrate-free growth medium. High-performance liquid chromatography purification was performed after pH-selective ammonium sulfate precipitation and size-exclusion chromatography. Intact mass analysis and peptide mass fingerprinting identified the 13,484-Da protein to be a mass homolog to the YvgO protein construct sequenced from Bacillus cereus AH 1134. Further analysis via amino-terminal sequencing also revealed the existence of four distinct yet equally efficacious YvgO variants differing only within the first four N-terminal residues. YvgO was found to be remarkably stable, maintaining its antifungal activity under a wide pH and temperature range. When assayed against the toxigenic species Byssochlamys fulva H25, the selected primary filamentous fungal indicator, the MIC was estimated to be 1.5 ppm. Candida albicans 3153 was more resistant, exhibiting MICs between 25 and 800 ppm, depending on growth conditions. YvgO is unique among antifungals, showing no known sequential or functional homology to the typical classes of antifungal proteins, including common membrane-acting agents such as cellulases and glucanases. Due to its activity against an array of pathogenic and spoilage fungi, the potentials for clinical, agricultural, and food-processing applications are encouraging. PMID- 22307286 TI - Investigations of Salmonella enterica serovar newport infections of oysters by using immunohistochemistry and knockout mutagenesis. AB - The consumption of raw oysters is an important risk factor in the acquisition of food-borne disease, with Salmonella being one of a number of pathogens that have been found in market oysters. Previous work by our lab found that Salmonella was capable of surviving in oysters for over 2 months under laboratory conditions, and this study sought to further investigate Salmonella's tissue affinity and mechanism of persistence within the oysters. Immunohistochemistry was used to show that Salmonella was capable of breaching the epithelial barriers, infecting the deeper connective tissues of the oysters, and evading destruction by the oysters' phagocytic hemocytes. To further investigate the mechanism of these infections, genes vital to the function of Salmonella's two main type III secretion systems were disrupted and the survivability of these knockout mutants within oysters was assayed. When the Salmonella pathogenicity island 1 and 2 mutant strains were exposed to oysters, there were no detectable deficiencies in their abilities to survive, suggesting that Salmonella's long-term infection of oysters does not rely upon these two important pathogenicity islands and must be due to some other, currently unknown, mechanism. PMID- 22307287 TI - Complete genome sequence of virulence-enhancing Siphophage VHS1 from Vibrio harveyi. AB - Vibrio harveyi siphophage 1 (VHS1) is a tailed phage with an icosahedral head of approximately 66 nm in diameter and an unornamented, flexible tail of approximately 153 nm in length. When Vibrio harveyi 1114GL is lysogenized with VHS1, its virulence for the black tiger shrimp (Penaeus monodon) increases by more than 100 times, and this coincides with production of a toxin(s) associated with shrimp hemocyte agglutination. Curiously, the lysogen does not show increased virulence for the whiteleg shrimp (Penaeus [Litopenaeus] vannamei). Here we present and annotate the complete, circular genome of VHS1 (81,509 kbp; GenBank accession number JF713456). By software analysis, the genome contains 125 putative open reading frames (ORFs), all of which appear to be located on the same DNA strand, similar to the case for many other bacteriophages. Most of the putative ORFs show no significant homology to known sequences in GenBank. Notable exceptions are ORFs for a putative DNA polymerase and putative phage structural proteins, including a portal protein, a phage tail tape measure protein, and a phage head protein. The last protein was identified as a component of the species specific toxin mixture described above as being associated with agglutination of hemocytes from P. monodon. PMID- 22307288 TI - Elevated carbon dioxide alters the structure of soil microbial communities. AB - Pyrosequencing analysis of 16S rRNA genes was used to examine impacts of elevated CO(2) (eCO(2)) on soil microbial communities from 12 replicates each from ambient CO(2) (aCO(2)) and eCO(2) settings. The results suggest that the soil microbial community composition and structure significantly altered under conditions of eCO(2), which was closely associated with soil and plant properties. PMID- 22307289 TI - Acquired tolerance to oxidative stress in Bifidobacterium longum 105-A via expression of a catalase gene. AB - For improvement of tolerance to oxidative stress in Bifidobacterium longum 105-A, we introduced the Bacillus subtilis catalase gene (katE) into it. The transformant showed catalase activity (39 U/mg crude protein) in the intracellular fraction, which increased survival by ~100-fold after a 1-h exposure to 4.4 mM H(2)O(2), decreased de novo H(2)O(2) accumulation, and increased survival in aerated cultures by 10(5)-fold at 24 h. The protection level was better than that conferred by exogenously added catalase. PMID- 22307290 TI - Abundance and genetic diversity of aerobic anoxygenic phototrophic bacteria of coastal regions of the pacific ocean. AB - Aerobic anoxygenic phototrophic (AAP) bacteria are photoheterotrophic microbes that are found in a broad range of aquatic environments. Although potentially significant to the microbial ecology and biogeochemistry of marine ecosystems, their abundance and genetic diversity and the environmental variables that regulate these properties are poorly understood. Using samples along nearshore/offshore transects from five disparate islands in the Pacific Ocean (Oahu, Molokai, Futuna, Aniwa, and Lord Howe) and off California, we show that AAP bacteria, as quantified by the pufM gene biomarker, are most abundant near shore and in areas with high chlorophyll or Synechococcus abundance. These AAP bacterial populations are genetically diverse, with most members belonging to the alpha- or gammaproteobacterial groups and with subclades that are associated with specific environmental variables. The genetic diversity of AAP bacteria is structured along the nearshore/offshore transects in relation to environmental variables, and uncultured pufM gene libraries suggest that nearshore communities are distinct from those offshore. AAP bacterial communities are also genetically distinct between islands, such that the stations that are most distantly separated are the most genetically distinct. Together, these results demonstrate that environmental variables regulate both the abundance and diversity of AAP bacteria but that endemism may also be a contributing factor in structuring these communities. PMID- 22307291 TI - Distinct ectomycorrhizospheres share similar bacterial communities as revealed by pyrosequencing-based analysis of 16S rRNA genes. AB - Analysis of the 16S rRNA gene sequences generated from Xerocomus pruinatus and Scleroderma citrinum ectomycorrhizospheres revealed that similar bacterial communities inhabited the two ectomycorrhizospheres in terms of phyla and genera, with an enrichment of the Burkholderia genus. Compared to the bulk soil habitat, ectomycorrhizospheres hosted significantly more Alpha-, Beta-, and Gammaproteobacteria. PMID- 22307292 TI - Rerouting carbon flux to enhance photosynthetic productivity. AB - The bioindustrial production of fuels, chemicals, and therapeutics typically relies upon carbohydrate inputs derived from agricultural plants, resulting in the entanglement of food and chemical commodity markets. We demonstrate the efficient production of sucrose from a cyanobacterial species, Synechococcus elongatus, heterologously expressing a symporter of protons and sucrose (cscB). cscB-expressing cyanobacteria export sucrose irreversibly to concentrations of >10 mM without culture toxicity. Moreover, sucrose-exporting cyanobacteria exhibit increased biomass production rates relative to wild-type strains, accompanied by enhanced photosystem II activity, carbon fixation, and chlorophyll content. The genetic modification of sucrose biosynthesis pathways to minimize competing glucose- or sucrose-consuming reactions can further improve sucrose production, allowing the export of sucrose at rates of up to 36.1 mg liter(-1) h illumination(-1). This rate of production exceeds that of previous reports of targeted, photobiological production from microbes. Engineered S. elongatus produces sucrose in sufficient quantities (up to ~80% of total biomass) such that it may be a viable alternative to sugar synthesis from terrestrial plants, including sugarcane. PMID- 22307293 TI - Diversity of symbiotic organs and bacterial endosymbionts of lygaeoid bugs of the families blissidae and lygaeidae (hemiptera: heteroptera: lygaeoidea). AB - Here we present comparative data on the localization and identity of intracellular symbionts among the superfamily Lygaeoidea (Insecta: Hemiptera: Heteroptera: Pentatomomorpha). Five different lygaeoid species from the families Blissidae and Lygaeidae (sensu stricto; including the subfamilies Lygaeinae and Orsillinae) were analyzed. Fluorescence in situ hybridization (FISH) revealed that all the bugs studied possess paired bacteriomes that are differently shaped in the abdomen and harbor specific endosymbionts therein. The endosymbionts were also detected in female gonads and at the anterior poles of developing eggs, indicating vertical transmission of the endosymbionts via ovarial passage, in contrast to the posthatch symbiont transmission commonly found among pentatomoid bugs (Pentatomomorpha: Pentatomoidea). Phylogenetic analysis based on 16S rRNA and groEL genes showed that the endosymbionts of Ischnodemus sabuleti, Arocatus longiceps, Belonochilus numenius, Orsillus depressus, and Ortholomus punctipennis constitute at least four distinct clades in the Gammaproteobacteria. The endosymbiont phylogeny did not agree with the host phylogeny based on the mitochondrial cytochrome oxidase I (COI) gene, but there was a local cospeciating pattern within the subfamily Orsillinae. Meanwhile, the endosymbiont of Belonochilus numenius (Lygaeidae: Orsillinae), although harbored in paired bacteriomes as in other lygaeoid bugs of the related genera Nysius, Ortholomus, and Orsillus, was phylogenetically close to "Candidatus Rohrkolberia cinguli," the endosymbiont of Chilacis typhae (Lygaeoidea: Artheneidae), suggesting an endosymbiont replacement in this lineage. The diverse endosymbionts and the differently shaped bacteriomes may reflect independent evolutionary origins of the endosymbiotic systems among lygaeoid bugs. PMID- 22307294 TI - Equine stomachs harbor an abundant and diverse mucosal microbiota. AB - Little is known about the gastric mucosal microbiota in healthy horses, and its role in gastric disease has not been critically examined. The present study used a combination of 16S rRNA bacterial tag-encoded pyrosequencing (bTEFAP) and fluorescence in situ hybridization (FISH) to characterize the composition and spatial distribution of selected gastric mucosal microbiota of healthy horses. Biopsy specimens of the squamous, glandular, antral, and any ulcerated mucosa were obtained from 6 healthy horses by gastroscopy and from 3 horses immediately postmortem. Pyrosequencing was performed on biopsy specimens from 6 of the horses and yielded 53,920 reads in total, with 631 to 4,345 reads in each region per horse. The microbiome segregated into two distinct clusters comprised of horses that were stabled, fed hay, and sampled at postmortem (cluster 1) and horses that were pastured on grass, fed hay, and biopsied gastroscopically after a 12-h fast (cluster 2). The types of bacteria obtained from different anatomic regions clustered by horse rather than region. The dominant bacteria in cluster 1 were Firmicutes (>83% reads/sample), mainly Streptococcus spp., Lactobacillus spp. and, Sarcina spp. Cluster 2 was more diverse, with predominantly Proteobacteria, Bacteroidetes, and Firmicutes, consisting of Actinobacillus spp. Moraxella spp., Prevotella spp., and Porphyromonas spp. Helicobacter sp. sequences were not identified in any of 53,920 reads. FISH (n = 9) revealed bacteria throughout the stomach in close apposition to the mucosa, with significantly more Streptococcus spp. present in the glandular region of the stomach. The equine stomach harbors an abundant and diverse mucosal microbiota that varies by individual. PMID- 22307295 TI - NAD(P)+-malic enzyme mutants of Sinorhizobium sp. strain NGR234, but not Azorhizobium caulinodans ORS571, maintain symbiotic N2 fixation capabilities. AB - C(4)-dicarboxylic acids appear to be metabolized via the tricarboxylic acid (TCA) cycle in N(2)-fixing bacteria (bacteroids) within legume nodules. In Sinorhizobium meliloti bacteroids from alfalfa, NAD(+)-malic enzyme (DME) is required for N(2) fixation, and this activity is thought to be required for the anaplerotic synthesis of pyruvate. In contrast, in the pea symbiont Rhizobium leguminosarum, pyruvate synthesis occurs via either DME or a pathway catalyzed by phosphoenolpyruvate carboxykinase (PCK) and pyruvate kinase (PYK). Here we report that dme mutants of the broad-host-range Sinorhizobium sp. strain NGR234 formed nodules whose level of N(2) fixation varied from 27 to 83% (plant dry weight) of the wild-type level, depending on the host plant inoculated. NGR234 bacteroids had significant PCK activity, and while single pckA and single dme mutants fixed N(2) at reduced rates, a pckA dme double mutant had no N(2)-fixing activity (Fix( )). Thus, NGR234 bacteroids appear to synthesize pyruvate from TCA cycle intermediates via DME or PCK pathways. These NGR234 data, together with other reports, suggested that the completely Fix(-) phenotype of S. meliloti dme mutants may be specific to the alfalfa-S. meliloti symbiosis. We therefore examined the ME-like genes azc3656 and azc0119 from Azorhizobium caulinodans, as azc3656 mutants were previously shown to form Fix(-) nodules on the tropical legume Sesbania rostrata. We found that purified AZC3656 protein is an NAD(P)(+) malic enzyme whose activity is inhibited by acetyl-coenzyme A (acetyl-CoA) and stimulated by succinate and fumarate. Thus, whereas DME is required for symbiotic N(2) fixation in A. caulinodans and S. meliloti, in other rhizobia this activity can be bypassed via another pathway(s). PMID- 22307296 TI - Dynamics of the linuron hydrolase libA gene pool size in response to linuron application and environmental perturbations in agricultural soil and on-farm biopurification systems. AB - libA, a gene encoding a novel type of linuron hydrolase, was recently identified in the linuron-mineralizing Variovorax sp. strain SRS16. In order to assess the contribution of libA to linuron degradation in environmental settings, libA abundance was monitored in response to the application of linuron and to environmental perturbations in agricultural soil microcosms and microcosms simulating the matrix of on-farm biopurification systems. libA numbers were measured by real-time PCR and linked to reported data of Variovorax community composition and linuron mineralization capacity. In the soil microcosms and one biopurification system setup, libA numbers responded to the application of linuron and environmental changes in congruency with the modulation of linuron mineralization capacity and the occurrence of a particular Variovorax phylotype (phylotype A). However, in another biopurification system setup, no such correlations were found. Our data suggest that in the simulated environmental settings, the occurrence of libA can be linked to the linuron mineralization capacity and that libA is primarily hosted by Variovorax phylotype A strains. However, the results also suggest that, apart from libA, other, as-yet-unknown isofunctional genes play an important role in linuron mineralization in the environment. PMID- 22307297 TI - Establishment of characteristic gut bacteria during development of the honeybee worker. AB - Previous surveys have shown that adult honeybee (Apis mellifera) workers harbor a characteristic gut microbiota that may play a significant role in bee health. For three major phylotypes within this microbiota, we have characterized distributions and abundances across the life cycle and among gut organs. These distinctive phylotypes, called Beta, Firm-5, and Gamma-1 (BFG), were assayed using quantitative PCR, fluorescent in situ hybridization (FISH) microscopy, and the experimental manipulation of inoculation routes within developing bees. Adult workers (9 to 30 days posteclosion) contained a large BFG microbiota with a characteristic distribution among gut organs. The crop and midgut were nearly devoid of these phylotypes, while the ileum and rectum together contained more than 95% of the total BFG microbiota. The ileum contained a stratified community in which the Beta and Gamma-1 phylotypes dominated, filling the longitudinal folds of this organ. Deep sequencing of 16S rRNA genes showed clear differences among communities in midgut, ileum, and rectum. In contrast with older workers, larvae and newly emerged workers contain few or no bacteria, and their major food source, bee bread, lacks most characteristic phylotypes. In experiments aimed at determining the route of inoculation, newly emerged workers (NEWs) sometimes acquired the typical phylotypes through contact with older workers, contact with the hive, and emergence from the brood cell; however, transmission was patchy in these assays. Our results outline a colonization pattern for the characteristic phylotypes through A. mellifera ontogeny. We propose the names "Candidatus Snodgrassella alvi" and "Candidatus Gilliamella apicola" for the Beta and Gamma-1 phylotypes, respectively. PMID- 22307298 TI - Vibrio parahaemolyticus in Rhode Island coastal ponds and the estuarine environment of narragansett bay. AB - Quantification of the abundance of Vibrio parahaemolyticus in water and oysters from Rhode Island showed the presence of environmental strains and low levels of potentially pathogenic strains when water temperatures were >=18 degrees C, with peak levels in late July to early August. A higher abundance of the trh gene than of the tdh gene was observed. PMID- 22307299 TI - Longitudinal study of the persistence of antimicrobial-resistant campylobacter strains in distinct Swine production systems on farms, at slaughter, and in the environment. AB - The objectives of this study were to compare and characterize the prevalence of antimicrobial-resistant (AR) Campylobacter in conventional and antimicrobial-free (ABF) production systems on farms, at slaughter, and in the environment. Fecal and environmental samples were collected from ABF farms (pigs, 1,239; environment, 797) and conventional farms (pigs, 1,650; environment, 1,325). At slaughter, we collected samples from carcasses, including postevisceration swabs, postchill swabs, and mesenteric lymph nodes from ABF systems (postevisceration swabs, 182; postchill swabs, 199; mesenteric lymph nodes, 184) and conventional systems (postevisceration swabs, 272; postchill swabs, 271; mesenteric lymph nodes, 255) at separate processing facilities. We also sampled the processing plant environment, including truck and lairage floor swab samples (ABF, 115; conventional, 90). Overall, a total of 2,908 Campylobacter isolates, including Campylobacter coli (farm, 2,557, 99.8%; slaughter, 341, 98.3%) and Campylobacter jejuni (farm, 4, 0.2%; slaughter, 6, 1.7%), were isolated in the study. There was no significant difference in the prevalence of Campylobacter between ABF and conventionally raised pigs (farrowing, P = 0.20; nursery, P = 0.06; finishing, P = 0.24) and the environment (P = 0.37). At slaughter, Campylobacter was isolated from all of the stages, including postchill. The highest frequencies of resistance were exhibited against tetracycline (ABF, 48.2%; conventional, 88.3%). Ciprofloxacin-resistant C. coli isolates were observed in conventionally raised (17.1%) and ABF (1.2%) pigs (P = 0.11). Antimicrobial use data from conventional farms indicated significant associations between oxytetracycline use and tetracycline resistance in the nursery pigs (P = 0.01), between tiamulin exposure and azithromycin and erythromycin resistance in nursery (P < 0.01) and finishing (P < 0.01) pigs, and between enrofloxacin exposure and ciprofloxacin and nalidixic acid resistance in farrowing (P < 0.01) and nursery (P < 0.01) pigs. Identical antimicrobial resistance profiles were observed in the pigs and their environments on farms and at slaughter. In summary, our results highlight the persistence and dissemination of AR Campylobacter from farm to slaughter in ABF and conventionally raised pigs and their environments. PMID- 22307300 TI - Rapid and simple cryopreservation of anaerobic ammonium-oxidizing bacteria. AB - A quick and simple protocol for long-term cryopreservation of anaerobic ammonium oxidizing bacteria (anammox bacteria) was developed. After 29 weeks of preservation at -80 degrees C, activity recovery for all tested cultures under at least one of the applied sets of preservation conditions was observed. Growth recovery was also demonstrated for a single-cell culture of "Candidatus Kuenenia stuttgartiensis." PMID- 22307301 TI - Seropathotypes, Phylogroups, Stx subtypes, and intimin types of wildlife-carried, shiga toxin-producing escherichia coli strains with the same characteristics as human-pathogenic isolates. AB - The objectives of this study were to investigate the presence of Shiga toxin producing Escherichia coli (STEC) strains in wildlife that have spread in Europe, living near human settlements; to analyze their epidemiological role in maintenance and transmission to domestic livestock; and to assess the potential health risk of wildlife-carried strains. STEC strains were recovered from 53% of roe deer, 8.4% of wild boars, and 1.9% of foxes sampled in the northwest of Spain (Galicia). Of the 40 serotypes identified, 21 were classified as seropathotypes associated with human disease, accounting for 81.5% of the wildlife-carried STEC strains, including the enterohemorrhagic serotypes O157:H7-D-eae-gamma1, O26:[H11]-B1-eae-beta1, O121:H19-B1-eae-epsilon1, and O145:[H28]-D-eae-gamma1. None of the wildlife-carried strains belonged to the highly pathogenic serotype O104:H4-B1 from the recent Germany outbreak. Forty percent of wildlife-carried STEC strains shared serotypes, phylogroups, intimin types, and Stx profiles with isolates from human patients from the same geographic area. Furthermore, wildlife carried strains belonging to serotypes O5:HNM-A, O26:[H11]-B1, O76:H19-B1, O145:[H28]-D, O146:H21-B1, and O157:H7-D showed pulsed-field gel electrophoresis (PFGE) profiles with >85% similarity to human-pathogenic STEC strains. We also found a high level of similarity among STEC strains of serotypes O5:HNM-A, O26:[H11]-B1, and O145:HNM-D of bovine (feces and beef) and wildlife origins. Interestingly, O146:H21-B1, the second most frequently detected serotype in this study, is commonly associated with human diarrhea and isolated from beef and vegetables sold in Galicia. Importantly, at least 3 STEC isolates from foxes (O5:HNM-A-eae-beta1, O98:[H21]-B1-eae-zeta1, and O146:[H21]-B1) showed characteristics similar to those of human STEC strains. In conclusion, roe deer, wild boar, and fox in Galicia are confirmed to be carriers of STEC strains potentially pathogenic for humans and seem to play an important role in the maintenance of STEC. PMID- 22307302 TI - Piglets are a source of pathogenic Yersinia enterocolitica on fattening-pig farms. AB - To study the origin and spread of Yersinia enterocolitica among pigs, fecal and blood samples were repeatedly taken on a fattening farm. A few piglets were found to be already infected on breeding farms. After the piglets were mixed, the infection spread through the whole unit. Eventually, all the pigs excreted the pathogen. PMID- 22307303 TI - Characterization of Esterase A, a Pseudomonas stutzeri A15 Autotransporter. AB - Autotransporters are a widespread family of proteins, generally known as virulence factors produced by Gram-negative bacteria. In this study, the esterase A (EstA) autotransporter of the rice root-colonizing beneficial bacterium Pseudomonas stutzeri A15 was characterized. A multiple sequence alignment identified EstA as belonging to clade II of the GDSL esterase family. Autologous overexpression allowed the investigation of several features of both autotransporter proteins and GDSL esterases. First, the correctly folded autotransporter was shown to be present in the membrane fraction. Unexpectedly, after separation of the membrane fraction, EstA was detected in the N laurylsarcosine soluble fraction. However, evidence is presented for the surface exposure of EstA based on fluorescent labeling with EstA specific antibodies. Another remarkable feature is the occurrence of a C-terminal leucine residue instead of the canonical phenylalanine or tryptophan residue. Replacement of this residue with a phenylalanine residue reduced the stability of the beta-barrel. Regarding the esterase passenger domain, we show the importance of the catalytic triad residues, with the serine and histidine residues being more critical than the aspartate residue. Furthermore, the growth of an estA-negative mutant was not impaired and cell mobility was not disabled compared to the wild type. No specific phenotype was detected for an estA-negative mutant. Overall, P. stutzeri A15 EstA is a new candidate for the surface display of proteins in environmentally relevant biotechnological applications. PMID- 22307304 TI - Differential biofilm formation and chemical disinfection resistance of sessile cells of Listeria monocytogenes strains under monospecies and dual-species (with Salmonella enterica) conditions. AB - This study aimed to investigate the possible influence of bacterial intra- and interspecies interactions on the ability of Listeria monocytogenes and Salmonella enterica to develop mixed-culture biofilms on an abiotic substratum, as well as on the subsequent resistance of sessile cells to chemical disinfection. Initially, three strains from each species were selected and left to attach and form biofilms on stainless steel (SS) coupons incubated at 15 degrees C for 144 h, in periodically renewable tryptone soy broth (TSB), under either monoculture or mixed-culture (mono-/dual-species) conditions. Following biofilm formation, mixed-culture sessile communities were subjected to 6-min disinfection treatments with (i) benzalkonium chloride (50 ppm), (ii) sodium hypochlorite (10 ppm), (iii) peracetic acid (10 ppm), and (iv) a mixture of hydrogen peroxide (5 ppm) and peracetic acid (5 ppm). Results revealed that both species reached similar biofilm counts (ca. 10(5) CFU cm(-2)) and that, in general, interspecies interactions did not have any significant effect either on the biofilm-forming ability (as this was assessed by agar plating enumeration of the mechanically detached biofilm bacteria) or on the antimicrobial resistance of each individual species. Interestingly, pulsed-field gel electrophoresis (PFGE) analysis clearly showed that the three L. monocytogenes strains did not contribute at the same level either to the formation of mixed-culture sessile communities (mono-/dual species) or to their antimicrobial recalcitrance. Additionally, the simultaneous existence inside the biofilm structure of S. enterica cells seemed to influence the occurrence and resistance pattern of L. monocytogenes strains. In sum, this study highlights the impact of microbial interactions taking place inside a mixed culture sessile community on both its population dynamics and disinfection resistance. PMID- 22307305 TI - Identification and characterization of gamma-aminobutyric acid uptake system GabPCg (NCgl0464) in Corynebacterium glutamicum. AB - Corynebacterium glutamicum is widely used for industrial production of various amino acids and vitamins, and there is growing interest in engineering this bacterium for more commercial bioproducts such as gamma-aminobutyric acid (GABA). In this study, a C. glutamicum GABA-specific transporter (GabP(Cg)) encoded by ncgl0464 was identified and characterized. GabP(Cg) plays a major role in GABA uptake and is essential to C. glutamicum growing on GABA. GABA uptake by GabP(Cg) was weakly competed by l-Asn and l-Gln and stimulated by sodium ion (Na(+)). The K(m) and V(max) values were determined to be 41.1 +/- 4.5 MUM and 36.8 +/- 2.6 nmol min(-1) (mg dry weight [DW])(-1), respectively, at pH 6.5 and 34.2 +/- 1.1 MUM and 67.3 +/- 1.0 nmol min(-1) (mg DW)(-1), respectively, at pH 7.5. GabP(Cg) has 29% amino acid sequence identity to a previously and functionally identified aromatic amino acid transporter (TyrP) of Escherichia coli but low identities to the currently known GABA transporters (17% and 15% to E. coli GabP and Bacillus subtilis GabP, respectively). The mutant RES167 Deltancgl0464/pGXKZ9 with the GabP(Cg) deletion showed 12.5% higher productivity of GABA than RES167/pGXKZ9. It is concluded that GabP(Cg) represents a new type of GABA transporter and is potentially important for engineering GABA-producing C. glutamicum strains. PMID- 22307306 TI - Pathogenicity and infection cycle of Vibrio owensii in larviculture of the ornate spiny lobster (Panulirus ornatus). AB - The type strain of Vibrio owensii (DY05) was isolated during an epizootic of aquaculture-reared larvae (phyllosomas) of the ornate spiny lobster (Panulirus ornatus). V. owensii DY05 was formally demonstrated to be the etiological agent of a disease causing rapid and reproducible larval mortality with pathologies similar to those seen during disease epizootics. Vectored challenge via the aquaculture live feed organism Artemia (brine shrimp) caused consistent cumulative mortality rates of 84 to 89% after 72 h, in contrast to variable mortality rates seen after immersion challenge. Histopathological examination of vector-challenged phyllosomas revealed bacterial proliferation in the midgut gland (hepatopancreas) concomitant with epithelial cell necrosis. A fluorescent protein-labeled V. owensii DY05 transconjugant showed dispersal of single cells in the foregut and hepatopancreas 6 h postexposure, leading to colonization of the entire hepatopancreas within 18 h and eventually systemic infection. V. owensii DY05 is a marine enteropathogen highly virulent to P. ornatus phyllosoma that uses vector-mediated transmission and release from host association to a planktonic existence to perpetuate transfer. This understanding of the infection process will improve targeted biocontrol strategies and enhance the prospects of commercially viable larviculture for this valuable spiny lobster species. PMID- 22307307 TI - Effect of soybean coumestrol on Bradyrhizobium japonicum nodulation ability, biofilm formation, and transcriptional profile. AB - Flavonoids, secondary plant metabolites which mainly have a polyphenolic structure, play an important role in plant-microbe communications for nitrogen fixing symbiosis. Among 10 polyphenolic compounds isolated from soybean roots in our previous study, coumestrol showed the highest antioxidant activity. In this study, its effect on the soybean nodulation was tested. The soybean symbiont Bradyrhizobium japonicum USDA110 pretreated with 20 MUM coumestrol enhanced soybean nodulation by increasing the number of nodules 1.7-fold compared to the control. We also tested the effect of coumestrol on B. japonicum biofilm formation. At a concentration of 2 MUM, coumestrol caused a higher degree of biofilm formation than two major soybean isoflavonoids, genistein and daidzein, although no biofilm formation was observed at a concentration of 20 MUM each compound. A genome-wide transcriptional analysis was performed to obtain a comprehensive snapshot of the B. japonicum response to coumestrol. When the bacterium was incubated in 20 MUM coumestrol for 24 h, a total of 371 genes (139 upregulated and 232 downregulated) were differentially expressed at a 2-fold cutoff with a q value of less than 5%. No common nod gene induction was found in the microarray data. However, quantitative reverse transcription-PCR (qRT-PCR) data showed that incubation for 12 h resulted in a moderate induction (ca. 2 fold) of nodD1 and nodABC, indicating that soybean coumestrol is a weak inducer of common nod genes. In addition, disruption of nfeD (bll4952) affected the soybean nodulation by an approximate 30% reduction in the average number of nodules. PMID- 22307308 TI - Quantification of human fecal bifidobacterium species by use of quantitative real time PCR analysis targeting the groEL gene. AB - Quantitative real-time PCR assays targeting the groEL gene for the specific enumeration of 12 human fecal Bifidobacterium species were developed. The housekeeping gene groEL (HSP60 in eukaryotes) was used as a discriminative marker for the differentiation of Bifidobacterium adolescentis, B. angulatum, B. animalis, B. bifidum, B. breve, B. catenulatum, B. dentium, B. gallicum, B. longum, B. pseudocatenulatum, B. pseudolongum, and B. thermophilum. The bifidobacterial chromosome contains a single copy of the groEL gene, allowing the determination of the cell number by quantification of the groEL copy number. Real time PCR assays were validated by comparing fecal samples spiked with known numbers of a given Bifidobacterium species. Independent of the Bifidobacterium species tested, the proportion of groEL copies recovered from fecal samples spiked with 5 to 9 log(10) cells/g feces was approximately 50%. The quantification limit was 5 to 6 log(10) groEL copies/g feces. The interassay variability was less than 10%, and variability between different DNA extractions was less than 23%. The method developed was applied to fecal samples from healthy adults and full-term breast-fed infants. Bifidobacterial diversity in both adults and infants was low, with mostly <=3 Bifidobacterium species and B. longum frequently detected. The predominant species in infant and adult fecal samples were B. breve and B. adolescentis, respectively. It was possible to distinguish B. catenulatum and B. pseudocatenulatum. We conclude that the groEL gene is a suitable molecular marker for the specific and accurate quantification of human fecal Bifidobacterium species by real-time PCR. PMID- 22307309 TI - Listeria monocytogenes shows temperature-dependent and -independent responses to salt stress, including responses that induce cross-protection against other stresses. AB - The food-borne pathogen Listeria monocytogenes experiences osmotic stress in many habitats, including foods and the gastrointestinal tract of the host. During transmission, L. monocytogenes is likely to experience osmotic stress at different temperatures and may adapt to osmotic stress in a temperature-dependent manner. To understand the impact of temperature on the responses this pathogen uses to adapt to osmotic stress, we assessed genome-wide changes in the L. monocytogenes H7858 transcriptome during short-term and long-term adaptation to salt stress at 7 degrees C and 37 degrees C. At both temperatures, the short-term response to salt stress included increased transcript levels of sigB and SigB regulated genes, as well as mrpABCDEFG, encoding a sodium/proton antiporter. This antiporter was found to play a role in adaptation to salt stress at both temperatures; DeltamrpABCDEFG had a significantly longer lag phase than the parent strain in BHI plus 6% NaCl at 7 degrees C and 37 degrees C. The short-term adaptation to salt stress at 7 degrees C included increased transcript levels of two genes encoding carboxypeptidases that modify peptidoglycan. These carboxypeptidases play a role in the short-term adaptation to salt stress only at 7 degrees C, where the deletion mutants had significantly different lag phases than the parent strain. Changes in the transcriptome at both temperatures suggested that exposure to salt stress could provide cross-protection to other stresses, including peroxide stress. Short-term exposure to salt stress significantly increased H(2)O(2) resistance at both temperatures. These results provide information for the development of knowledge-based intervention methods against this pathogen, as well as provide insight into potential mechanisms of cross-protection. PMID- 22307310 TI - Commercially distributed meat as a potential vehicle for community-acquired methicillin-resistant Staphylococcus aureus. AB - The incidence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection has been increasing; however, the sources of infection remain unclear. Therefore, we investigated the involvement of meat as a possible mediator of CA-MRSA infection. We examined the distribution of MRSA strains in commercially distributed raw meat samples (n = 197) and diarrheal stool samples of outpatients (n = 1,287) that were collected in Oita Prefecture, Japan, between 2003 and 2009 for routine legal inspections. Fourteen MRSA strains were isolated from three meat and 11 stool samples. Among these, seven isolates from three meat and four stool samples exhibited the same epidemiological marker profiles [coagulase type III, staphylococcal enterotoxin C, staphylococcal chromosomal cassette mec (SCCmec) type IV, ST8, spa type 606 (t1767), and toxic shock syndrome toxin-1 (TSST-1) producing type]. Furthermore, of the seven strains, three isolates from two meat samples and one stool sample collected in 2007 exhibited completely identical characteristics with respect to phage open reading frame (ORF) typing, pulsed-field gel electrophoresis, and drug susceptibility profiles. The results suggest that commercially distributed meat could play a role in the prevalence of CA-MRSA in the community. PMID- 22307311 TI - Abrupt temporal fluctuations in the chicken fecal microbiota are explained by its gastrointestinal origin. AB - One of the main challenges in understanding the composition of fecal microbiota is that it can consist of microbial mixtures originating from different gastrointestinal (GI) segments. Here, we addressed this challenge for broiler chicken feces using a direct 16S rRNA gene-sequencing approach combined with multivariate statistical analyses. Broiler feces were chosen because of easy sampling and the importance for pathogen transmission to the human food chain. Feces were sampled daily for 16 days from chickens with and without a feed structure-induced stimulation of the gastric barrier function. Overall, we found four dominant microbial phylogroups in the feces. Two of the phylogroups were related to clostridia, one to lactobacilli, and one to Escherichia/Shigella. The relative composition of these phylogroups showed apparent stochastic temporal fluctuations in feces. Analyses of dissected chickens at the end of the experiment, however, showed that the two clostridial phylogroups were correlated to the microbiota in the cecum/colon and the small intestine, while the upper gut (crop and gizzard) microbiota was correlated to the lactobacillus phylogroup. In addition, chickens with a stimulated gizzard also showed less of the proximate GI dominating bacterial group in the feces, supporting the importance of the gastric barrier function. In conclusion, our results suggest that GI origin is a main determinant for the chicken fecal microbiota composition. This knowledge will be important for future understanding of factors affecting shedding of both harmful and beneficial gastrointestinal bacteria through feces. PMID- 22307313 TI - Treatment with bisphenol A and methoxychlor results in the growth of human breast cancer cells and alteration of the expression of cell cycle-related genes, cyclin D1 and p21, via an estrogen receptor-dependent signaling pathway. AB - Various endocrine disrupting chemicals (EDCs) are exogenous compounds found in the environment and have the potential to interfere with the endocrine system and hormonal regulation. Among EDCs, bisphenol A (BPA) and 1,1,1-trichloro-2,2-bis(4 methoxyphenol)-ethane [methoxychlor (MXC)] have estrogenic activity resulting in a variety of dysfunctions in the E2-mediated response by binding to estrogen receptors (ERs), causing human health problems such as abnormal reproduction and carcinogenesis. In this study, we investigated the effects of BPA and MXC on cell proliferation facilitated by ER signaling in human breast cancer cells. MCF-7 cells are known to be ERalpha-positive and to be a highly E2-responsive cancer cell line; these cells are, therefore, a useful in vitro model for detecting estrogenic activity in response to EDCs. We evaluated cancer cell proliferation following BPA and MXC treatment using an MTT assay. We analyzed alterations in the expression of genes associated with the cell cycle in MCF-7 cells by semi quantitative reverse-transcription PCR following treatment with BPA or MXC compared to EtOH. To determine whether BPA and MXC stimulate cancer cell growth though ER signaling, we co-treated the cells with agonists (propyl pyrazoletriol, PPT; and diarylpropionitrile, DPN) or an antagonist (ICI 182,780) of ER signaling and reduced ERalpha gene expression via siRNA in MCF-7 cells before treatment with EDCs. These studies confirmed the carcinogenicity of EDCs in vitro. As a result, BPA and MXC induced the cancer cell proliferation by the upregulation of genes that promote the cell cycle and the downregulation of anti-proliferative genes, especially ones affecting the G1/S transition via ERalpha signaling. These collective results confirm the carcinogenicity of these EDCs in vitro. Further studies are required to determine whether EDCs promote carcinogenesis in vivo. PMID- 22307312 TI - Novel high-rank phylogenetic lineages within a sulfur spring (Zodletone Spring, Oklahoma), revealed using a combined pyrosequencing-sanger approach. AB - The utilization of high-throughput sequencing technologies in 16S rRNA gene-based diversity surveys has indicated that within most ecosystems, a significant fraction of the community could not be assigned to known microbial phyla. Accurate determination of the phylogenetic affiliation of such sequences is difficult due to the short-read-length output of currently available high throughput technologies. This fraction could harbor multiple novel phylogenetic lineages that have so far escaped detection. Here we describe our efforts in accurate assessment of the novelty and phylogenetic affiliation of selected unclassified lineages within a pyrosequencing data set generated from source sediments of Zodletone Spring, a sulfide- and sulfur-rich spring in southwestern Oklahoma. Lineage-specific forward primers were designed for 78 putatively novel lineages identified within the pyrosequencing data set, and representative nearly full-length small-subunit (SSU) rRNA gene sequences were obtained by pairing those primers with reverse universal bacterial primers. Of the 78 lineages tested, amplifiable products were obtained for 52, 32 of which had at least one nearly full-length sequence that was representative of the lineage targeted. Analysis of phylogenetic affiliation of the obtained Sanger sequences identified 5 novel candidate phyla and 10 novel candidate classes (within Fibrobacteres, Planctomycetes, and candidate phyla BRC1, GN12, TM6, TM7, LD1, WS2, and GN06) in the data set, in addition to multiple novel orders and families. The discovery of multiple novel phyla within a pilot study of a single ecosystem clearly shows the potential of the approach in identifying novel diversities within the rare biosphere. PMID- 22307314 TI - A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing. AB - Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as nanoparticles or cell therapies), the limited predictivity of traditional tests for human health effects, duration and costs of current approaches, and animal welfare considerations. The latter holds especially true in the context of the scheduled 2013 marketing ban on cosmetic ingredients tested for systemic toxicity. Based on a major analysis of the status of alternative methods (Adler et al., 2011) and its independent review (Hartung et al., 2011), the present report proposes a roadmap for how to overcome the acknowledged scientific gaps for the full replacement of systemic toxicity testing using animals. Five whitepapers were commissioned addressing toxicokinetics, skin sensitization, repeated-dose toxicity, carcinogenicity, and reproductive toxicity testing. An expert workshop of 35 participants from Europe and the US discussed and refined these whitepapers, which were subsequently compiled to form the present report. By prioritizing the many options to move the field forward, the expert group hopes to advance regulatory science. PMID- 22307315 TI - Assessing the necessity of chimpanzee experimentation. PMID- 22307316 TI - Spectral deciphering of the interaction between an intramolecular hydrogen bonded ESIPT drug, 3,5-dichlorosalicylic acid, and a model transport protein. AB - The present work demonstrates a detailed characterization of the interaction of a bio-active drug molecule 3,5-dichlorosalicyclic acid (3,5DCSA) with a model transport protein Bovine Serum Albumin (BSA). The drug molecule is a potential candidate exhibiting Excited-State Intramolecular Proton Transfer (ESIPT) reaction and the modulation of ESIPT photophysics within the bio-environment of the protein has been exploited spectroscopically to monitor the drug-protein binding interaction. Apart from evaluating the binding constant (K (+/-10%) = 394 M(-1)) the probable location of the neutral drug molecule within the protein cavity (hydrophobic subdomain IIA) is explored by AutoDock-based blind docking simulation. The rotational relaxation dynamics of the drug within the protein has been interpreted on the lexicon of the two-step and wobbling-in-cone model. Circular dichroism (CD) spectroscopy delineates the effect of drug binding on the protein secondary structure in terms of decrease of alpha-helical content of BSA with increasing drug concentration. Also the esterase activity of the drug:protein conjugate system is found to be reduced in comparison to the native protein. PMID- 22307317 TI - Help-seeking for emotional problems in major depression : findings of the 2006 Estonian health survey. AB - To study help-seeking among the general population and people with major depression. 12-month help-seeking for emotional problems was assessed in a cross sectional 2006 Estonian Health Survey. Non-institutionalized individuals aged 18 84 years (n = 6,105) were interviewed. A major depressive episode was assessed using the Mini-International Neuropsychiatric Interview. The factors associated with help-seeking, received help, and health service use were analyzed. The prevalence of 12-month help-seeking for emotional symptoms was 4.8%. The rate of 12-month help-seeking in the depressed sample was 34.1%. Depressed people used non-mental health services 1.5-3 times more than non-depressed persons even when adjusted for the chronic somatic disorder. Only one third of depressed persons sought help, which was most of all associated with severity of depression. Underdiagnosis and undertreatment of depression leads to an increased use of expensive but non-specific health services by depressed persons. PMID- 22307318 TI - The end of iodide? Cobalt complex redox shuttles in DSSCs. AB - This article focuses on the promise and progress of replacing the ubiquitous triiodide/iodide electrolyte with cobalt poly-pyridine complex redox shuttles in dye-sensitized solar cells, DSSCs. Issues which require further research will also be presented. PMID- 22307319 TI - Angiotensin converting enzyme gene polymorphism is associated with severity of coronary artery disease in men with high total cholesterol levels. AB - This study examines whether renin-angiotensin-aldosterone system gene polymorphisms: ACE (encoding for angiotensin converting enzyme) c.2306-117_404 I/D, AGTR1 (encoding for angiotensin II type-1 receptor) c.1080*86A>C and CYP11B2 (encoding for aldosterone synthase) c.-344C>T are associated with the extension of coronary atherosclerosis in a group of 647 patients who underwent elective coronary angiography. The extension of CAD was evaluated using the Gensini score. The polymorphisms were determined by PCR and RFLP assays. The associations between genotypes and the extent of coronary atherosclerosis were tested by the Kruskal-Wallis test, followed by pairwise comparisons using Wilcoxon test. The population has been divided into groups defined by: sex, smoking habit, past myocardial infarction, BMI (>, <= 25), age (>, <= 55), diabetes mellitus, level of total cholesterol (>, <= 200 mg/dl), LDL cholesterol (>, <= 130 mg/dl), HDL cholesterol (>, <= 40 mg/dl), triglycerides (>, <= 150 mg/dl). Significant associations between the ACE c.2306-117_404 I/D polymorphism and the Gensini score in men with high total cholesterol levels (P(Kruskal-Wallis) = 0.008; P(adjusted) = 0.009), high level of LDL cholesterol (P(Kruskal-Wallis) = 0.016; P(adjusted) = 0.028) and low level of HDL cholesterol (P(Kruskal-Wallis) = 0.04; P(adjusted) = 0.055) have been found. No association between the AGTR1 c.1080*86A>C and CYP11B2 c.-344C>T and the Gensini score has been found. These results suggest that men who carry ACE c.2306-117_404 DD genotype and have high total cholesterol, high LDL cholesterol and low HDL cholesterol levels may be predisposed to the development of more severe CAD. PMID- 22307320 TI - Practice guidelines for central venous access: a report by the American Society of Anesthesiologists Task Force on Central Venous Access. PMID- 22307322 TI - NPs -- heart hormones that regulate brown fat? AB - Thermogenesis in brown adipose tissue (BAT) is well characterized as being under the control of the sympathetic nervous system. The energy-burning capacity of BAT makes it an attractive target for anti-obesity therapies. However, previous attempts to manipulate BAT's sympathetic activation have lacked specificity. In this issue of the JCI, Bordicchia et al. provide new data indicating that cardiac natriuretic peptides (NPs) are also able to activate thermogenic machinery in adipose tissue. Their findings suggest a novel strategy to increase energy dissipation in adipose tissue, independent of adrenergic receptors. PMID- 22307323 TI - Unraveling the mystery of the hygiene hypothesis through Helicobacter pylori infection. AB - Epidemiological studies have revealed an inverse association between Helicobacter pylori infection and the incidence of allergic asthma. This association is consistent with the hygiene hypothesis, which posits that exposure to microbes early in life prevents the later development of allergic diseases, and has been reproduced in mouse models of asthma. In this issue of the JCI, Oertli and colleagues report that H. pylori infection in neonates elicits tolerogenic DCs that produce IL-18, which drive the generation of Tregs that subsequently protect the mice from allergic asthma. This finding strengthens the intriguing link between pathogen exposure and allergic disease. PMID- 22307324 TI - Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. AB - The ability of mammals to resist body fat accumulation is linked to their ability to expand the number and activity of "brown adipocytes" within white fat depots. Activation of beta-adrenergic receptors (beta-ARs) can induce a functional "brown like" adipocyte phenotype. As cardiac natriuretic peptides (NPs) and beta-AR agonists are similarly potent at stimulating lipolysis in human adipocytes, we investigated whether NPs could induce human and mouse adipocytes to acquire brown adipocyte features, including a capacity for thermogenic energy expenditure mediated by uncoupling protein 1 (UCP1). In human adipocytes, atrial NP (ANP) and ventricular NP (BNP) activated PPARgamma coactivator-1alpha (PGC-1alpha) and UCP1 expression, induced mitochondriogenesis, and increased uncoupled and total respiration. At low concentrations, ANP and beta-AR agonists additively enhanced expression of brown fat and mitochondrial markers in a p38 MAPK-dependent manner. Mice exposed to cold temperatures had increased levels of circulating NPs as well as higher expression of NP signaling receptor and lower expression of the NP clearance receptor (Nprc) in brown adipose tissue (BAT) and white adipose tissue (WAT). NPR-C(-/-) mice had markedly smaller WAT and BAT depots but higher expression of thermogenic genes such as Ucp1. Infusion of BNP into mice robustly increased Ucp1 and Pgc-1alpha expression in WAT and BAT, with corresponding elevation of respiration and energy expenditure. These results suggest that NPs promote "browning" of white adipocytes to increase energy expenditure, defining the heart as a central regulator of adipose tissue biology. PMID- 22307325 TI - ChIP sequencing of cyclin D1 reveals a transcriptional role in chromosomal instability in mice. AB - Chromosomal instability (CIN) in tumors is characterized by chromosomal abnormalities and an altered gene expression signature; however, the mechanism of CIN is poorly understood. CCND1 (which encodes cyclin D1) is overexpressed in human malignancies and has been shown to play a direct role in transcriptional regulation. Here, we used genome-wide ChIP sequencing and found that the DNA bound form of cyclin D1 occupied the regulatory region of genes governing chromosomal integrity and mitochondrial biogenesis. Adding cyclin D1 back to Ccnd1(-/-) mouse embryonic fibroblasts resulted in CIN gene regulatory region occupancy by the DNA-bound form of cyclin D1 and induction of CIN gene expression. Furthermore, increased chromosomal aberrations, aneuploidy, and centrosome abnormalities were observed in the cyclin D1-rescued cells by spectral karyotyping and immunofluorescence. To assess cyclin D1 effects in vivo, we generated transgenic mice with acute and continuous mammary gland-targeted cyclin D1 expression. These transgenic mice presented with increased tumor prevalence and signature CIN gene profiles. Additionally, interrogation of gene expression from 2,254 human breast tumors revealed that cyclin D1 expression correlated with CIN in luminal B breast cancer. These data suggest that cyclin D1 contributes to CIN and tumorigenesis by directly regulating a transcriptional program that governs chromosomal stability. PMID- 22307326 TI - DC-derived IL-18 drives Treg differentiation, murine Helicobacter pylori-specific immune tolerance, and asthma protection. AB - Persistent colonization with the gastric bacterial pathogen Helicobacter pylori causes gastritis and predisposes infected individuals to gastric cancer. Conversely, it is also linked to protection from allergic, chronic inflammatory, and autoimmune diseases. We demonstrate here that H. pylori inhibits LPS-induced maturation of DCs and reprograms DCs toward a tolerance-promoting phenotype. Our results showed that DCs exposed to H. pylori in vitro or in vivo failed to induce T cell effector functions. Instead, they efficiently induced expression of the forkhead transcription factor FoxP3, the master regulator of Tregs, in naive T cells. Depletion of DCs in mice infected with H. pylori during the neonatal period was sufficient to break H. pylori-specific tolerance. DC depletion resulted in improved control of the infection but also aggravated T cell-driven immunopathology. Consistent with the mouse data, DCs infiltrating the gastric mucosa of human H. pylori carriers exhibited a semimature DC-SIGN(+)HLA DR(hi)CD80(lo)CD86(lo) phenotype. Mechanistically, the tolerogenic activity of H. pylori-experienced DCs was shown to require IL-18 in vitro and in vivo; DC derived IL-18 acted directly on T cells to drive their conversion to Tregs. CD4(+)CD25(+) Tregs from infected wild-type mice but not Il18(-/-) or Il18r1(-/-) mice prevented airway inflammation and hyperresponsiveness in an experimental model of asthma. Taken together, our results indicate that tolerogenic reprogramming of DCs ensures the persistence of H. pylori and protects against allergic asthma in a process that requires IL-18. PMID- 22307327 TI - Anti-ganglioside antibody internalization attenuates motor nerve terminal injury in a mouse model of acute motor axonal neuropathy. AB - In the Guillain-Barre syndrome subform acute motor axonal neuropathy (AMAN), Campylobacter jejuni enteritis triggers the production of anti-ganglioside Abs (AGAbs), leading to immune-mediated injury of distal motor nerves. An important question has been whether injury to the presynaptic neuron at the neuromuscular junction is a major factor in AMAN. Although disease modeling in mice exposed to AGAbs indicates that complement-mediated necrosis occurs extensively in the presynaptic axons, evidence in humans is more limited, in comparison to the extensive injury seen at nodes of Ranvier. We considered that rapid AGAb uptake at the motor nerve terminal membrane might attenuate complement-mediated injury. We found that PC12 rat neuronal cells rapidly internalized AGAb, which were trafficked to recycling endosomes and lysosomes. Consequently, complement mediated cytotoxicity was attenuated. Importantly, we observed the same AGAb endocytosis and protection from cytotoxicity in live mouse nerve terminals. AGAb uptake was attenuated following membrane cholesterol depletion in vitro and ex vivo, indicating that this process may be dependent upon cholesterol-enriched microdomains. In contrast, we observed minimal AGAb uptake at nodes of Ranvier, and this structure thus remained vulnerable to complement-mediated injury. These results indicate that differential endocytic processing of AGAbs by different neuronal and glial membranes might be an important modulator of site-specific injury in acute AGAb-mediated Guillain-Barre syndrome subforms and their chronic counterparts. PMID- 22307328 TI - Essential role of gastric gland mucin in preventing gastric cancer in mice. AB - Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides (O-glycans) having terminal alpha1,4 linked N-acetylglucosamine residues (alphaGlcNAc). Previously, we identified human alpha1,4-N-acetylglucosaminyltransferase (alpha4GnT), which is responsible for the O-glycan biosynthesis and characterized alphaGlcNAc function in suppressing Helicobacter pylori in vitro. In the present study, we engineered A4gnt(-/-) mice to better understand its role in vivo. A4gnt(-/-) mice showed complete lack of alphaGlcNAc expression in gastric gland mucin. Surprisingly, all the mutant mice developed gastric adenocarcinoma through a hyperplasia-dysplasia carcinoma sequence in the absence of H. pylori infection. Microarray and quantitative RT-PCR analysis revealed upregulation of genes encoding inflammatory chemokine ligands, proinflammatory cytokines, and growth factors, such as Ccl2, Il-11, and Hgf in the gastric mucosa of A4gnt(-/-) mice. Further supporting an important role for this O-glycan in cancer progression, we also observed significantly reduced alphaGlcNAc in human gastric adenocarcinoma and adenoma. Our results demonstrate that the absence of alphaGlcNAc triggers gastric tumorigenesis through inflammation-associated pathways in vivo. Thus, alphaGlcNAc terminated gastric mucin plays dual roles in preventing gastric cancer by inhibiting H. pylori infection and also suppressing tumor-promoting inflammation. PMID- 22307329 TI - DYRK2 priming phosphorylation of c-Jun and c-Myc modulates cell cycle progression in human cancer cells. AB - Dysregulation of the G(1)/S transition in the cell cycle contributes to tumor development. The oncogenic transcription factors c-Jun and c-Myc are indispensable regulators at this transition, and their aberrant expression is associated with many malignancies. Degradation of c-Jun/c-Myc is a critical process for the G(1)/S transition, which is initiated upon phosphorylation by glycogen synthase kinase 3 beta (GSK3beta). However, a specific kinase or kinases responsible for priming phosphorylation events that precede this GSK3beta modification has not been definitively identified. Here, we found that the dual specificity tyrosine phosphorylation-regulated kinase DYRK2 functions as a priming kinase of c-Jun and c-Myc. Knockdown of DYRK2 in human cancer cells shortened the G(1) phase and accelerated cell proliferation due to escape of c Jun and c-Myc from ubiquitination-mediated degradation. In concert with these results, silencing DYRK2 increased cell proliferation in human cancer cells, and this promotion was completely impeded by codeprivation of c-Jun or c-Myc in vivo. We also found marked attenuation of DYRK2 expression in multiple human tumor samples. Downregulation of DYRK2 correlated with high levels of unphosphorylated c-Jun and c-Myc and, importantly, with invasiveness of human breast cancers. These results reveal that DYRK2 regulates tumor progression through modulation of c-Jun and c-Myc. PMID- 22307330 TI - CLASPs prevent irreversible multipolarity by ensuring spindle-pole resistance to traction forces during chromosome alignment. AB - Loss of spindle-pole integrity during mitosis leads to multipolarity independent of centrosome amplification. Multipolar-spindle conformation favours incorrect kinetochore-microtubule attachments, compromising faithful chromosome segregation and daughter-cell viability. Spindle-pole organization influences and is influenced by kinetochore activity, but the molecular nature behind this critical force balance is unknown. CLASPs are microtubule-, kinetochore- and centrosome associated proteins whose functional perturbation leads to three main spindle abnormalities: monopolarity, short spindles and multipolarity. The first two reflect a role at the kinetochore-microtubule interface through interaction with specific kinetochore partners, but how CLASPs prevent spindle multipolarity remains unclear. Here we found that human CLASPs ensure spindle-pole integrity after bipolarization in response to CENP-E- and Kid-mediated forces from misaligned chromosomes. This function is independent of end-on kinetochore microtubule attachments and involves the recruitment of ninein to residual pericentriolar satellites. Distinctively, multipolarity arising through this mechanism often persists through anaphase. We propose that CLASPs and ninein confer spindle-pole resistance to traction forces exerted during chromosome congression, thereby preventing irreversible spindle multipolarity and aneuploidy. PMID- 22307331 TI - The use of androgens or androgen-modulating agents in poor responders undergoing in vitro fertilization: a systematic review and meta-analysis. AB - BACKGROUND: The aim of this meta-analysis was to evaluate the role of androgens or androgen-modulating agents on the probability of pregnancy achievement in poor responders undergoing IVF. METHODS: Medline, EMBASE, CENTRAL, Scopus and Web of Science databases were searched for the identification of randomized controlled trials evaluating the administration of testosterone, dehydroepiandrosterone (DHEA), aromatase inhibitors, recombinant luteinizing hormone (rLH) and recombinant human chorionic gonadotrophin (rhCG) before or during ovarian stimulation of poor responders. RESULTS: In two trials involving 163 patients, pretreatment with transdermal testosterone was associated with an increase in clinical pregnancy [risk difference (RD): +15%, 95% confidence interval (CI): +3 to +26%] and live birth rates (RD: +11%, 95% CI: +0.3 to +22%) in poor responders undergoing ovarian stimulation for IVF. No significant differences in clinical pregnancy and live birth rates were observed between patients who received DHEA and those who did not. Similarly, (i) the use of aromatase inhibitors, (ii) addition of rLH and (iii) addition of rhCG in poor responders stimulated with rFSH for IVF were not associated with increased clinical pregnancy rates. In the only eligible study that provided data, live birth rate was increased in patients who received rLH when compared with those who did not (RD: +19%, 95% CI:+1 to +36%). CONCLUSIONS: Based on the limited available evidence, transdermal testosterone pretreatment seems to increase clinical pregnancy and live birth rates in poor responders undergoing ovarian stimulation for IVF. There is insufficient data to support a beneficial role of rLH, hCG, DHEA or letrozole administration in the probability of pregnancy in poor responders undergoing ovarian stimulation for IVF. PMID- 22307333 TI - Degradation effect of diepoxide fixation on porcine endogenous retrovirus DNA in heart valves: molecular aspects. AB - PURPOSE: Xenotransplantations of porcine cells, tissues, and organs involve a risk of zoonotic viral infections in recipients, including by porcine endogenous retroviruses (PERVs), which are embedded the genome of all pigs. An appropriate preparation of porcine heart valves for transplantation can prevent retroviral infection. Therefore, the present study focuses on the effect of epoxy compounds and glutaraldehyde on the PERV presence in porcine heart valves prepared for clinical use. METHODS: Porcine aortic heart valves were fixed with ethylene glycol diglycidyl ether (EDGE) at 5 degrees C and 25 degrees C as well as with glutaraldehyde (GA) for 4 weeks. Salting out was used to isolate genomic DNA from native as well as EDGE- and GA-fixed fragments of valves every week. Quantification of PERV-A, PERV-B, and PERV-C DNA was performed by real-time quantitative polymerase chain reaction (QPCR). RESULTS: All subtypes of PERVs were detected in native porcine aortic heart valves. The reduction of the PERV-A, PERV-B, and PERV-C DNA copy numbers was observed in the heart valves which were EDGE-fixed at both temperatures, and in GA-fixed ones in the following weeks. After 7 and 14 days of EDGE cross-linking, significant differences between the investigated temperatures were found for the number of PERV-A and PERV-B copies. PERV DNA was completely degraded within the first week of EDGE fixation at 25 degrees C. CONCLUSIONS: EDGE fixation induces complete PERV genetic material degradation in porcine aortic heart valves. This suggests that epoxy compounds may be alternatively used in the preparation of bioprosthetic heart valves in future. PMID- 22307334 TI - Characterization and chondrogenic differentiation of menstrual blood-derived stem cells on a nanofibrous scaffold. AB - INTRODUCTION: The recent identification of menstrual blood-derived stem cells (MenSCs) as a unique population of stem cells has created enormous promise for tissue engineering. In this study, after characterization of MenSCs in comparison with bone marrow-derived stem cells (BMSCs), the potential of MenSCs seeded into electrospun, biodegradable, nanofibrous scaffolds in order to engineer cartilage was evaluated. METHODS: MenSCs and BMSCs were isolated by discontinuous density gradient centrifugation and plastic adherence. After characterization of MenSCs compared with BMSCs, MenSC differentiation into chondrocytes was investigated on a nanofibrous scaffold with specific growth and differentiation factors. The scaffold was prepared from polycaprolactone (PCL) and its surface was modified by plasma treatment. RESULTS: Flow cytometric analysis of expanded cells showed that MenSCs typically express some surface and intracellular markers associated with BMSCs. But marked expression of OCT-4 and the absence of STRO1 distinguished them from mesenchymal stem cells obtained from bone marrow. Based on scanning electron microscope images, the MenSCs were strongly anchored to the highly porous scaffold, which they penetrated and proliferated on. The scaffold contained an extensive cartilage-like extracellular matrix with about 50% greater glycosaminoglycan content than control MenSCs differentiated in a two-dimensional (2D) culture system (p<0.05). Considerable amounts of proteoglycan were produced by the cells differentiated on the scaffold, as demonstrated by Alcian blue staining. Unlike undifferentiated MenSCs, cells differentiated on the scaffold had strong immunoreactivity with monoclonal antibody against collagen type II. CONCLUSIONS: The evidence presented in this study introduces MenSCs as a suitable stem cell population candidate for cartilage tissue engineering. PMID- 22307332 TI - Inner nuclear membrane proteins: impact on human disease. AB - In the past decade, the inner nuclear membrane has become a focus of research on inherited diseases. A heterogeneous group of genetic disorders known as laminopathies have been described that result from mutations in genes encoding nuclear lamins, intermediate filament proteins associated with the inner nuclear membrane. Mutations in genes encoding integral inner nuclear membrane proteins, many of which bind to nuclear lamins, also cause diseases that sometimes are very similar to those caused by lamin gene mutations. The pathogenic mechanisms that underlie these diseases, which often selectively affect different tissues or organ systems despite the near-ubiquitous expression of the proteins, are only beginning to be elucidated. The unfolding story of the laminopathies provides a remarkable example of how research in basic cell biology has impacted upon medicine and human health. PMID- 22307335 TI - Performing encapsulation of dsDNA and a polymerase chain reaction (PCR) inside nanocontainers using the inverse miniemulsion process. AB - We report the encapsulation of dsDNA molecules with a defined number of base pairs (476 bp and 790 bp) and their subsequent amplification by polymerase chain reaction (PCR) inside nanosized polymeric capsules/droplets. In the first set of experiments, the dsDNA template and PCR reagents were encapsulated in crosslinked potato starch using the inverse (water-in-oil) miniemulsion technique. After redispersion of the capsules in a water-surfactant mixture, PCR was performed inside the crosslinked starch nanocapsules. In the second set of experiments, the PCR was performed inside the aqueous nanodroplets before capsule formation, and then each miniemulsion droplet was covered with a polybutylcyanoacrylate (PBCA) shell which was formed through anionic polymerization directly at the droplet interface. The PCR efficiency was quantitatively evaluated by fluorescence spectroscopy, using a DNA-specific dye called SYBR(r) Green which intercalates between the base pairs of the dsDNA. PMID- 22307336 TI - Brassinin induces G1 phase arrest through increase of p21 and p27 by inhibition of the phosphatidylinositol 3-kinase signaling pathway in human colon cancer cells. AB - The phosphatidylinositol 3-kinase (PI3K) signaling pathway is activated in a broad spectrum of human cancers, including colon cancer. The natural product brassinin is a type of indole compound derived from cruciferous vegetables, and has been shown to have anti-proliferative effects against cancer for both in vivo and in vitro models. Here, we show for the first time that brassinin inhibits cell growth in human colon cancer cells by arresting the cell cycle at the G1 phase via inhibition of the PI3K signaling pathway. Brassinin increased the expression of p21 and p27, resulting in hypophosphorylation of the retinoblastoma gene (RB). Knockdown of p21 or p27 by each siRNA significantly repressed G1 phase arrest induced by brassinin. The increase of p21 and p27 was associated with inhibition of the PI3K signaling pathway. In addition, exogenous expression of constitutively active Akt represses the cell cycle arrest at G1 phase induced by brassinin. These results suggest the possibility that brassinin inhibits the PI3K signaling pathway and upregulates the expression of p21 and p27, thereby inducing G1 phase arrest. PMID- 22307337 TI - An evolving case of concurrent eosinophilic esophagitis and eosinophilic gastroenteritis. PMID- 22307338 TI - Cryptogenic hepatitis and bartonellosis. PMID- 22307359 TI - A computational study on the intriguing mechanisms of the gas-phase thermal activation of methane by bare [Ni(H)(OH)]+. AB - A detailed computational study on the reaction mechanisms of the thermal activation of methane by the bare complex [Ni(H)(OH)](+) has been conducted. The experimentally observed reaction features, i.e. the ligand exchange Ni(H) -> Ni(CH(3)), the H/D scrambling between the incoming methane and the hydrido ligand of the nickel complex, the spectator-like behavior of the OH ligand, and the relatively moderate reaction efficiency of 6% relative to the collision rate of the ion/molecule reaction, can be explained by considering three competing mechanisms, and a satisfactory agreement between experiment and theory has been found. PMID- 22307361 TI - Aspiration pneumonia and death in Huntington's disease. AB - Huntington's disease (HD) is a progressive neurodegenerative autosomal dominant disease characterized by choreatic and hypokinetic movements, disturbed behaviour, and cognitive decline. Pneumonia is the most common cause of death, followed by cardiovasculair diseases. It has been suggested that choking is the causative underlying factor for pneumonia in HD. As a detailed specification of the type of pneumonia has never been performed, we analyzed the records of our Brain Bank containing 224 cases to determine the exact cause of death and type of pneumonia. The conclusion is that the majority (86.8%) of our HD patients where the cause of death could be identified died from aspiration pneumonia. PMID- 22307362 TI - Antibodies in the treatment of aplastic anemia. AB - Antibodies have been the cornerstone of treatment of acquired aplastic anemia for more than 25 years. Treatment with antithymocyte globulin (ATG) is considered pivotal and the addition of cyclosporine improves the overall response rate. This antibody is heterogeneous and horse ATG is apparently more effective than rabbit ATG. Several issues remain unsolved in relation to the combination of ATG and cyclosporine: cost, toxicity and late clonal disorders. In recent years, alternative immunosuppressive therapy has been proposed and new antibodies have emerged: porcine ATG, alemtuzumab, daclizumab, and rituximab. Experience with these antibodies is limited to a few studies with alemtuzumab being the most promising, but the results are interesting and provocative. More studies are needed to find the perfect antibody. PMID- 22307363 TI - Microvesicles in health and disease. AB - Microvesicles (or MVs) are plasma membrane-derived vesicles released from most eukaryotic cells constitutively during early apoptosis or at higher levels after chemical or physical stress conditions. This review looks at some of the functions of MVs in terms of intercellular communication and ensuant signal transduction, including the transport of proteins (unconventional protein export) as well as of mRNA and microRNA. MVs also have roles in membrane repair, the removal of misfolded proteins, and in the control of apoptosis. We also discuss the role MVs have been shown to have in invasive growth and metastasis as well as in hypoxia in tumours and cerebral ischaemia. The association of MVs in infectious and autoimmune disease is also summarised together with their possible use as therapeutic agents. PMID- 22307364 TI - Talin, vinculin and nestin expression in orofacial muscles of dystrophin deficient mdx mice. AB - The activity of cytoskeletal proteins like talin, vinculin and nestin increases in muscle that regenerates. Little is known about their role or at least their expression in the process of regeneration in masticatory muscles of mdx mice, a model of Duchenne muscular dystrophy. To determine a potential role of cytoskeletal proteins in the regeneration process of mdx masticatory muscles, we examined the expression of talin 1, talin 2, vinculin and nestin in 100-day-old control and mdx mice using quantitative RT-PCR, Western blot analyses and histochemistry. The protein expression of talin 1, talin 2, nestin and vinculin in mdx muscles remained unchanged as compared with normal mice. However, in mdx masseter it was found a relative increase of nestin compared to controls. The protein expression of talin 1 and vinculin tended to be increased in mdx tongue and talin 2 to diminish in mdx masseter and temporal muscle. In mdx mice, we found significantly lower percentage of transcripts coding for nestin, talin 1, talin 2 and vinculin in masseter (p < 0.05) and temporal muscle (p < 0.001). In contrast, the mRNA expression of nestin was found to be increased in mdx tongue. Activated satellite cells, myoblasts and immature regenerated muscle fibres in mdx masseter and temporal revealed positive staining for nestin. The findings of the presented work suggest dystrophin-lack-associated changes in the expression of cytoskeletal proteins in mdx masticatory muscles could be compensatory for dystrophin absence. The expression of nestin may serve as an indicator for the regeneration in the orofacial muscles. PMID- 22307365 TI - The comparison of laparoscopic pyelolithotomy and percutaneous nephrolithotomy in the treatment of solitary large renal pelvic stones. AB - The aim of the study is to investigate whether laparoscopic pyelolithotomy (LPL) could find a place in the management of large renal pelvic stones which are generally considered as excellent indications for percutaneous nephrolithotomy (PNL). Between 2006 and 2009, 26 consecutive patients with large (>4 cm(2)) renal pelvic stones were treated by LPL and their charts were compared to 26 match paired patients treated with PNL during the same period. The patients were matched for age, BMI, stone size and location as well as presence of congenital anomalies. Perioperative and postoperative findings were compared. The mean age, mean stone size, rate of congenital anomalies, history open renal surgery and shock wave lithotripsy were similar in both groups (p > 0.05). The mean operation time was 138.40 +/- 51.19 (range 70-240) min in LPL group as compared to 57.92 +/ 21.12 (range 40-110) min in PNL group (p < 0.0001). There was one (3.8%) open conversion in the LPL group due to dense perirenal adhesions making the dissection difficult. The ureteropelvic junction (UPJ) obstruction concomitant to pelvic stones was successfully repaired laparoscopically in two cases. The mean drop in postoperative hemoglobin level was 0.9 +/- 0.6 (range 0-2) g/dl in LPL group and 1.7 +/- 1.1 (range 0-4) g/dl in PNL group (p = 0.024). Hospitalization was significantly shorter in PNL than LPL group (p = 0.0001). Stone-free rates were similar. Laparoscopic pyelolithotomy is associated with a longer operation time, is more invasive, and requires more skills when compared to PNL. However, LPL is associated with less blood loss. Laparoscopic pyelolithotomy is indicated for congenitally anomalous kidneys and especially in patients with concomitant UPJ. PMID- 22307366 TI - Colon perforation during percutaneous renal surgery: a 10-year experience in a single endourology centre. AB - The use of percutaneous renal surgery has been recently revolutionised with novel endourological instruments and techniques. However, the incidence, prevention and management of severe complications such as colon perforation still lack consensus. By presenting our 10-year experience, we would like to highlight the diagnosis and management of the rare complication of colon perforation. PMID- 22307367 TI - Letter to the editor regarding the article: "Prevalence of orthopedic complaints among endourologists and their compliance with radiation safety measures". PMID- 22307368 TI - Preclinical models that illuminate the bone metastasis cascade. AB - In this chapter currently available preclinical models of tumor progression and bone metastasis, including genetically engineered mice that develop primary and metastatic carcinomas and transplantable animal models, will be described. Understanding the multistep process of incurable bone metastasis is pivotal to the development of new therapeutic strategies. Novel technologies for imaging molecules or pathologic processes in cancers and their surrounding stroma have emerged rapidly and have greatly facilitated cancer research, in particular the cellular behavior of osteotropic tumors and their response to new and existing therapeutic agents. Optical imaging, in particular, has become an important tool in preclinical bone metastasis models, clinical trials and medical practice. Advances in experimental and clinical imaging will-in the long run-result in significant improvements in diagnosis, tumor localization, enhanced drug delivery and treatment. PMID- 22307369 TI - The role of bone microenvironment, vitamin D and calcium. AB - Starting first from Paget's "seed and soil" to the latest hypothesis about metastatic process involving the concept of a premetastatic niche, a large amount of data suggested the idea that metastatization is a multistep coordinated process with a high degree of efficiency. A specific subpopulation of cells with tumor-initiating and migratory capacity can selectively migrate toward sites that are able to promote survival, and/or proliferation of metastatic tumor cells through a microenvironment modification. Bone plays a pivotal role in this process, acting not only as a preferential site for cancer cells' homing and proliferation, due to a complex interplay between different cellular phenotypes such as osteoblasts and osteoclasts, but also as a source of bone marrow precursors that are able to facilitate the metastatic process in extra-skeletal disease. Moreover, bone microenvironment has the unique capacity to retain cancer stem cells in a quiescent status, acting as a reservoir that is able to cause a metastatic spread also many years after the resection of the primary tumor. To add a further level of complexity, these mechanisms are strictly regulated through the signalling through several soluble factors including PTH, vitamin D or calcium concentration. Understanding this complexity represents a major challenge in anti-cancer research and a mandatory step towards the development of new drugs potentially able not only to reduce the consequences of bone lesions but also to target the metastatization process from the "bone pre-neoplastic niche" to "visceral pre-neoplastic niches". PMID- 22307370 TI - Bisphosphonates: prevention of bone metastases in breast cancer. AB - Disease recurrence and distant metastases remain challenging for patients with breast cancer despite advances in early diagnosis, surgical expertise, and adjuvant therapy. Bone is the most common site for breast cancer metastasis, and the bone microenvironment plays a crucial role in harboring disseminated tumor cells (DTCs), a putative source of late relapse in and outside bone. Therefore, agents that affect bone metabolism might not only prevent the development of bone lesions but also provide meaningful reductions in the risk of relapse both in bone and beyond. Bisphosphonates bind to mineralized bone surfaces and are ingested by osteoclasts, wherein they inhibit osteolysis, thereby preventing the release of growth factors from the bone matrix. Therefore, the bone microenvironment becomes less conducive to survival and growth of DTCs and bone lesion formation. Recent trials of zoledronic acid in the adjuvant setting in breast cancer have demonstrated reduced disease recurrence in bone and other sites in premenopausal and postmenopausal women with early breast cancer. Based on the proven effect of bone protection during adjuvant endocrine therapy, new treatment guidelines recommend the routine use of bisphosphonates to prevent bone loss during adjuvant therapy, which may likely become the standard practice. PMID- 22307371 TI - Bisphosphonates: prevention of bone metastases in lung cancer. AB - In patients with lung cancer, bone is one of the most frequent sites of distant spread, with approximately 30% of patients developing skeletal metastases. About half of these patients will experience a skeletal-related event, the occurrence of which not only affects quality of life, but is also associated with poor prognosis. Bisphosphonates are currently the mainstay for treating bone metastases in patients with lung cancer, with proven beneficial effects on prevention and delay of skeletal complications. Their role in preventing the development of skeletal metastases, their anti-tumoral properties and their effect on survival remain to be elucidated. Other bone-targeted therapies are being investigated in phase II and III clinical trials and might expand the therapeutic arsenal in the near future. PMID- 22307372 TI - Bisphosphonates: prevention of bone metastases in prostate cancer. AB - Bone metastases and their associated morbidities are common in patients with advanced prostate cancer and other genitourinary (GU) malignancies. Zoledronic acid> (a bisphosphonate) has long been the mainstay of treatment for reducing the risk of skeletal-related events in patients with bone metastases from GU cancers, and denosumab (a monoclonal antibody directed against the receptor activator of nuclear factor kappa B ligand [RANKL]) has recently received approval for this indication in the United States. Preclinical data indicate that modifying the bone microenvironment may render it less conducive to metastasis, and emerging clinical findings suggest that the potential benefits from bone-directed therapies are not limited to reducing skeletal morbidity-these agents might help to improve survival and delay bone disease progression or even development of bone metastases (if used earlier in the disease course). This chapter reviews the rationale and recent clinical data supporting an antimetastatic role for bone directed therapies in patients with GU malignancies. PMID- 22307373 TI - Targeting bone in myeloma. AB - Myeloma bone disease (BD) not only impairs quality of life, but is also associated with impaired survival. Studies of the biology underlying BD support the notion that the increased osteoclastogenesis and suppressed osteoblastogenesis is both a consequence and a necessity for tumour growth and clonal expansion. Survival and expansion of the myeloma clone are dependent on its interactions with bone elements; thus, targeting these interactions should have anti-myeloma activities. Indeed, both experimental and clinical findings indicate that bone-targeted therapies, not only improve BD, but also create an inhospitable environment for myeloma cell growth and survival, favouring improved clinical outcome. This chapter summarizes recent progress in our understandings of the biology of myeloma BD, highlighting the role of osteoclasts and osteoblasts in this process and how they can be targeted therapeutically. Unravelling the mechanisms underlying myeloma-bone interactions will facilitate the development of novel therapeutic agents to treat BD, which as a consequence are likely to improve the clinical outcome of myeloma patients. PMID- 22307374 TI - Combinations of bisphosphonates and classical anticancer drugs: a preclinical perspective. AB - Bone metastases are frequent complications in advanced breast and prostate cancer among others, resulting in increased risk of fractures, pain, hypercalcaemia of malignancy and a reduction in patient independence and mobility. Bisphosphonates (BPs) are in wide clinical use for the treatment of cancer-induced bone disease associated with advanced cancer, due to their potent ability to reduce skeletal related events (SREs) and improve quality of life. Despite the profound effect on bone health, the majority of clinical studies have failed to demonstrate an overall survival benefit of BP therapy. There is increasing preclinical evidence to suggest that inclusion of the most potent nitrogen-containing BPs (NBPs) in combination therapy results in increased antitumour effects and improved survival, but that the particular schedules used are of key importance to achieve optimal benefit. Recent clinical data have suggested that there may be effects of adjuvant NBP therapy on breast tumours outside the skeleton. These findings have led to renewed interest in the use of BPs in cancer therapy, in particular how they can be included as part of adjuvant protocols. Here we review the key data reported from preclinical model systems investigating the effects of combination therapy including BPs with particular emphasis on breast and prostate cancer. PMID- 22307375 TI - Perspectives in the elderly patient: benefits and limits of bisphosphonates and denosumab. AB - Skeletal metastases affect a large percentage of the cancer population and contribute to a marked decrease in their quality of life and survival, in particular in elderly population. A future end-point of bone-protecting therapy is the demonstration of its ability to prevent or improve results in the treatment of metastatic disease, enlarging their clinical indications in metastatic and osteoporotic setting with different schedules. In this chapter we will discuss on pharmacokinetic and pharmacodynamic interactions of bisphosphonates in elderly, and the preclinical and clinical evidences of anticancer activity of bone-targeted therapies will be critically described. The clinical results of new targeted therapies (such as rank/rankl/OPG inhibition) will be reported both in bone metastatic and in adjuvant settings. Finally, the prevention of cancer treatment-induced bone loss (CTIBL) represents both in young and more in old patients an emerging issue in the bone health care. For this reason, this chapter will discuss the results of current therapies in this clinical setting. PMID- 22307376 TI - Denosumab: first data and ongoing studies on the prevention of bone metastases. AB - Bone metastases are associated with a major patient and healthcare burden resulting from the impact and the management of associated skeletal-related events (including spinal cord compression, pathologic fracture and surgery or radiation to bone). In preclinical studies, RANK Ligand inhibition has been shown to prevent the development of bone and some visceral metastases. Clinical studies are ongoing to evaluate whether the fully human monoclonal antibody denosumab, which targets RANK Ligand, can prevent the development of bone metastases in high risk patients. Findings from a phase 3 study in men with high-risk non-metastatic castration-resistant prostate cancer demonstrated that denosumab (120 mg every 4 weeks) significantly increased bone metastasis-free survival (primary endpoint) by 4.2 months (median) versus placebo (HR 0.85 [0.73, 0.98]; P = 0.028). This is the first study to demonstrate the clinical benefit of a bone-targeted agent in this setting. Further evaluation of denosumab in the prevention of metastatic disease is warranted and ongoing in other tumor types. PMID- 22307377 TI - Diagnostic and prognostic use of bone turnover markers. AB - The use of bone turnover markers in oncology includes monitoring of anticancer treatment in patients with malignant disease metastatic to the bones (therapeutic monitoring), predicting the risk of bone relapse in patients with a first diagnosis of potentially curative, early-stage malignant tumors (prognostic use), and making an early diagnosis of (microscopic) malignant bone disease in patients with a known malignant tumor to start early bone-targeted treatment and avoid skeletal-related events (diagnostic use). Concerning prognostic use, there is limited evidence for bone turnover markers to predict the occurrence of metachronous bone metastases in patients with early-stage malignant tumors, with serum PINP (N-terminal propeptide of procollagen type 1), ICTP (Carboxyterminal cross-linked telopeptide of type I collagen), bone sialoprotein (BSP), and tumor immunoexpression of BSP being the most promising candidates. Concerning diagnostic use, serum bone-specific alkaline phosphatise (BSAP), PINP and osteoprotegerin (OPG) were repeatedly shown to be associated with synchronous bone metastases in patients with breast or lung cancer, but sensitivity of these markers was too low to suggest that they might be preferred over conventional bone scans for the diagnosis of bone metastases. A somewhat higher sensitivity for the diagnosis of bone metastases was found for urinary NTx (N-terminal cross linked telopeptide of type I collagen) and serum ICTP in solid tumor patients, serum TRAcP-5b (Tartrate-resistant acid phosphatase type 5b) in patients with breast cancer and serum BSAP, PINP and OPG in prostate cancer patients. Both prognostic and diagnostic use of bone turnover markers are reviewed in this chapter. PMID- 22307378 TI - Osteolytic and osteoblastic bone metastases: two extremes of the same spectrum? AB - Normal bone development and maintenance are sustained through a balanced communication between osteoclasts and osteoblasts. Invasion of the bone compartment by cancer cells causes an imbalance in their activities and results in predominantly bone lysing or bone forming phenotypes depending on the origin of the cancer. Tumor-induced bone lesions usually exhibit disturbances of both cell types. Thus, osteoclast activity is activated in a predominantly osteoblastic lesion and vice versa. These cancer-induced bone responses favor the survival and growth of cancer cells in their new environment. Therapies that can restore the balance may limit the growth of cancer cells in the bone. The recent development of agents that target the osteolytic components of bone metastasis, including bisphosphonates and denosumab, showed promising results in osteolytic bone diseases such as multiple myeloma but were less effective in improving the osteoblastic bone disease found in prostate cancer. Thus, while osteolytic components are present in both osteoblastic and osteolytic bone lesions, inhibition of the osteolytic component is not sufficient to alter the vicious cycle leading to tumors with an osteoblastic phenotype. These observations suggest that osteolytic and osteoblastic bone metastases are not the same and tumor-induced osteoblastic and osteolytic activity play different roles in supporting their growth and survival. PMID- 22307379 TI - Aberrant expression of nuclear vimentin and related epithelial-mesenchymal transition markers in nasopharyngeal carcinoma. AB - Expression of vimentin and the epithelial to mesenchymal transition (EMT) markers E-cadherin, beta-catenin is essential for the progression of various human cancers. Our study aimed to investigate the aberrant localization E-cadherin, beta-catenin and vimentin, and their prognostic significance in 122 nasopharyngeal carcinoma (NPC) patients by immunohistochemistry and immunofluorescence. Our results showed that both membranous and cytoplasmic localization of E-cadherin staining were associated with lymph node metastasis (p = 0.000 and 0.005, respectively) and clinical stage (p = 0.000 and 0.007, respectively). High cytoplasmic beta-catenin correlated significantly with larger tumor size (p = 0.020), lymph node metastasis (p = 0.000) and advanced clinical stage (p = 0.036). However, no significant difference was observed between membranous beta-catenin and clinicopathologic features (p >= 0.05). High nuclear vimentin expression correlated significantly with positive lymph node metastasis (p = 0.000) and advanced clinical stage (p = 0.000). Multivariate analysis showed that nuclear vimentin and cytoplasmic E-cadherin were independent prognostic factors (p = 0.016 and 0.001, respectively), as well as M classification (p = 0.001). More importantly, patients with high coexpression of nuclear vimentin and cytoplasmic E-cadherin had shorter survival time (p = 0.000). Furthermore, high coexpression of these two proteins was closely associated with lymph node metastasis (p = 0.000) and advanced clinical stage (p = 0.000). Our studies provide convincing evidence that EMT may play an important role in the biological progression of NPC, and nuclear vimentin and cytoplasmic E-cadherin might have independent prognostic value in NPC patients and serve as novel targets for prognostic therapeutics. PMID- 22307381 TI - Comparison of the clinical presentation, treatment, and outcome of fulminant and acute myocarditis in children. AB - BACKGROUND: Myocarditis (MC) is an important cause of cardiac dysfunction in children. Fulminant MC is sometimes fatal, and sequelae may develop during follow up. We conducted a nationwide survey to determine the clinico-epidemiological features of MC in Japanese children and adolescents. METHODS AND RESULTS: Survey questionnaires were mailed to 627 hospitals, which were asked if they had treated MC patients aged between 1 month and 17 years during the period from January 1997 through December 2002. Responses were collected until December 2005, and data were collected and analyzed until January 2008. A total of 169 patients were reported: 64 fulminant cases, 89 acute cases, and 8 chronic cases. Incidence was 43.5 cases/year and 0.26 cases/100,000. Pathogens were identified in 37 patients; coxsackie virus accounted for 60%. Major cardiovascular manifestations at onset were congestive heart failure, refractory arrhythmia, and syncope in 70, 37, and 17 patients, respectively. Intravenous immunoglobulin was administered to 73 patients. Mechanical support seemed to be effective and life-saving. Among the 169 patients, 123 survived. Cardiovascular sequelae were reported in 49 patients. CONCLUSIONS: The survival rate for children with fulminant MC was disappointing. Overall, two-thirds of survivors had no sequelae. Mechanical support may reduce the mortality and the risk of clinical worsening. PMID- 22307382 TI - Using intermittent pneumatic compression therapy to improve quality of life for symptomatic patients with infrapopliteal diffuse peripheral obstructive disease. AB - BACKGROUND: Although the acute effect of intermittent pneumatic compression (IPC) therapy had been documented for patients with symptomatic peripheral arterial obstructive disease (PAOD), its efficacy in improving quality of life (QOL), especially for those with infrapopliteal diffuse lesions, remains unclear. METHODS AND RESULTS: Thirty-one patients with infrapopliteal diffuse or multiple segmental lesions were enrolled in the study. Based on receipt of IPC therapy (3 h daily for 3 months), patients were allocated to a study (n=23) or control (n=8) group. The 6-min walking test, transcutaneous oxygen tension (TcPO2), and QOL evaluated with the Short-Form 36 questionnaire were measured at the beginning and end of the study. In the QOL analysis, scores for physical functioning, physical and emotional role functioning, bodily pain, and general and mental health showed significant changes after IPC therapy. In the 6-min walking test, duration, and the initial and absolute claudication distances were significantly increased in the study group. The TcPO2 also significantly increased in the distal end of the target limb after IPC therapy. CONCLUSIONS: Patients at high risk for amputation with infrapopliteal diffuse or multiple segmental lesions can improve their walking ability, TcPO2 of the target limb and QOL after IPC therapy. PMID- 22307383 TI - Diagnostic pitfalls: a case of neurosarcoidosis mimicking tuberculous meningitis. PMID- 22307384 TI - Long-term follow-up of a phase 2 study of oral teriflunomide in relapsing multiple sclerosis: safety and efficacy results up to 8.5 years. AB - BACKGROUND: Teriflunomide, an oral disease-modifying therapy in development for patients with relapsing forms of multiple sclerosis (RMS), was well tolerated and effective in reducing magnetic resonance imaging (MRI) lesions in 179 RMS patients in a phase 2 36-week, placebo-controlled study. METHODS: A total of 147 patients who completed the core study entered an open-label extension. Teriflunomide patients continued their assigned dose, and placebo patients were re-allocated to teriflunomide, 7 mg/day or 14 mg/day. An interim analysis was performed at a cut-off on January 8 2010. RESULTS: The mean and median duration of study treatment, including both the core and extension phase, from baseline to the interim cut-off, was 5.6 years (standard deviation: 2.7 years) and 7.1 years (range: 0.05-8.5 years), respectively. Of 147 patients, 62 (42.2%) discontinued (19% due to treatment-emergent adverse events (TEAEs)). The most common TEAEs were mild infections, fatigue, sensory disturbances and diarrhoea. No serious opportunistic infections occurred, with no discontinuations due to infection. Asymptomatic alanine aminotransferase increases (<=3* upper limit of normal (ULN)) were common (7 mg, 64.2%; 14 mg, 62.1%); increases >3*ULN were similar across groups (7 mg, 12.3%; 14 mg, 12.1%). Mild decreases in neutrophil counts occurred; none led to discontinuation. The incidence of malignancies was comparable to that of the general population, and cases were not reminiscent of those observed in immunocompromised patients. Annualised relapse rates remained low, minimal disability progression was observed, with a dose-dependent benefit with teriflunomide 14 mg for several MRI parameters. CONCLUSION: Teriflunomide had a favourable safety profile for up to 8.5 years. PMID- 22307385 TI - Assessing brain connectivity at rest is clinically relevant in early multiple sclerosis. AB - OBJECTIVE: The present study aims to determine the clinical counterpart of brain resting-state networks reorganization recently evidenced in early multiple sclerosis. METHODS: Thirteen patients with early relapsing-remitting multiple sclerosis and 14 matched healthy controls were included in a resting state functional MRI study performed at 3 T. Data were analyzed using group spatial Independent Component Analysis using concatenation approach (FSL 4.1.3) and double regression analyses (SPM5) to extract local and global levels of connectivity inside various resting state networks (RSNs). Differences in global levels of connectivity of each network between patients and controls were assessed using Mann-Whitney U-test. In patients, relationship between clinical data (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite Score - MSFC) and global RSN connectivity were assessed using Spearman rank correlation. RESULTS: Independent component analysis provided eight consistent neuronal networks involved in motor, sensory and cognitive processes. For seven RSNs, the global level of connectivity was significantly increased in patients compared with controls. No significant decrease in RSN connectivity was found in early multiple sclerosis patients. MSFC values were negatively correlated with increased RSN connectivity within the dorsal frontoparietal network (r = -0.811, p = 0.001), the right ventral frontoparietal network (r = - 0.587, p = 0.045) and the prefronto-insular network (r = -0.615, p = 0.033). CONCLUSIONS: This study demonstrates that resting state networks reorganization is strongly associated with disability in early multiple sclerosis. These findings suggest that resting state functional MRI may represent a promising surrogate marker of disease burden. PMID- 22307386 TI - Selection of clinically useful angiogenesis-related biomarkers: an update. AB - Angiogenesis is a complex phenomenon that involves interaction between growth factors/cytokines and their receptors, and proteolytic enzymes and their inhibitors, which, in addition to and in accordance with their main roles, act together during this multistep process. Cancer angiogenesis is specific, because the same factors that enable angiogenesis are involved in the process of carcinogenesis. The aim of this review was to analyze the current knowledge regarding the significance of selected biomarkers in cancer angiogenesis, with emphasis on their prognostic value in the circulation. PMID- 22307387 TI - Three apoptotic genes are upregulated in a patient with Alzheimer's disease and well-differentiated squamous cell carcinoma. AB - We report the case of a 74-year-old man with Alzheimer's disease (AD) and an extensive ulcerative lesion on the right ear. AD is a neurodegenerative disease with progressive loss of memory and cognitive deterioration. It has been suggested that apoptotic cell injury and eventually cell death is a major contributor to the AD neurodegenerative process. The ulcerative lesion was surgically excised and the histological analysis reported a well-differentiated squamous cell carcinoma. Caspase-3 (CASP3) plays an important role in neuronal death during nervous system development and under certain pathological conditions. Furthermore, in vitro and in vivo studies reported elevated expression and activation of CASP3 in models of AD. Molecular epidemiological studies suggest that CASP3 may contribute to head and neck squamous cell carcinoma susceptibility and disease progression and that increased CASP3 expression is associated with tumors of the head. Also poly (ADP-ribose) polymerase 1 (PARP1) and the leucine zipper downregulated in cancer 1 (LDOC1) genes play a proapoptotic role. We therefore evaluated the differential expression of LDOC1, PARP1, and CASP3 mRNA in peripheral blood leukocytes of our patient. We found increased expression of all these genes compared with the expression in control subjects. PMID- 22307388 TI - Functional and structural characterization of the mammalian TREX-2 complex that links transcription with nuclear messenger RNA export. AB - Export of messenger RNA (mRNA) from the nucleus to the cytoplasm is a critical step in the gene expression pathway of eukaryotic cells. Here, we report the functional and structural characterization of the mammalian TREX-2 complex and show how it links transcription/processing with nuclear mRNA export. Mammalian TREX-2 is based on a germinal-centre associated nuclear protein (GANP) scaffold to which ENY2, PCID2 and centrins bind and depletion of any of these components inhibits mRNA export. The crystal structure of the GANP:ENY2 complex shows that two ENY2 chains interact directly with GANP, but they have different orientations from those observed on yeast Sac3. GANP is required to recruit ENY2 to nuclear pore complexes (NPCs), but ENY2 is not necessary to recruit GANP, which requires both its CID and MCM3AP domains, together with nucleoporin Nup153. GANP and ENY2 associate with RNA polymerase II and inhibition of mRNA processing redistributes GANP from NPCs into nuclear foci indicating that mammalian TREX-2 is associated with transcription. Thus, we implicate TREX-2 as an integral component of the mammalian mRNA export machinery where it links transcription and nuclear export by facilitating the transfer of mature mRNPs from the nuclear interior to NPCs. PMID- 22307389 TI - FRET studies of a landscape of Lac repressor-mediated DNA loops. AB - DNA looping mediated by the Lac repressor is an archetypal test case for modeling protein and DNA flexibility. Understanding looping is fundamental to quantitative descriptions of gene expression. Systematic analysis of LacI*DNA looping was carried out using a landscape of DNA constructs with lac operators bracketing an A-tract bend, produced by varying helical phasings between operators and the bend. Fluorophores positioned on either side of both operators allowed direct Forster resonance energy transfer (FRET) detection of parallel (P1) and antiparallel (A1, A2) DNA looping topologies anchored by V-shaped LacI. Combining fluorophore position variant landscapes allows calculation of the P1, A1 and A2 populations from FRET efficiencies and also reveals extended low-FRET loops proposed to form via LacI opening. The addition of isopropyl-beta-D-thio galactoside (IPTG) destabilizes but does not eliminate the loops, and IPTG does not redistribute loops among high-FRET topologies. In some cases, subsequent addition of excess LacI does not reduce FRET further, suggesting that IPTG stabilizes extended or other low-FRET loops. The data align well with rod mechanics models for the energetics of DNA looping topologies. At the peaks of the predicted energy landscape for V-shaped loops, the proposed extended loops are more stable and are observed instead, showing that future models must consider protein flexibility. PMID- 22307390 TI - Partially hydrolysed whey and soy-based infant formulas did not prevent allergic disease in high-risk children. PMID- 22307391 TI - Secondary fracture prevention. AB - Osteoporosis causes no symptoms until there is a fracture. Although screening for osteoporosis is recommended for some populations, patients may present with a fragility fracture. Such patients are at high risk for subsequent fractures. Despite this high risk and the presence of generally safe and effective osteoporosis therapy, only a minority of low trauma fracture patients have evaluation and treatment of underlying osteoporosis. A brief summary of the evaluation and medical treatment of the post-fracture patient is provided. Several institutions, integrated health systems, and countries have instituted programs to identify, evaluate, and treat fragility fracture patients. Such programs have had variable success. This article describes some of the programs that work, their cost-effectiveness, and the applicability to the generally non integrated US health care system. It is clear that better management of the post fracture patient (and other high-risk patients) will lead to fewer fractures, decreased morbidity and mortality, and long-term cost savings. PMID- 22307392 TI - Inspiratory capacity as a preoperative assessment of patients undergoing thoracic surgery. AB - Although inspiratory capacity (IC) is strongly associated with the disease severity of chronic obstructive pulmonary disease, there was no appropriate equation to compute predicted values for IC. Furthermore, whether assessment of IC can identify the risk of prolonged postoperative stay (PPS) in patients undergoing thoracic surgery also remains unclear. To evaluate whether %IC predicted, for which the new equation to compute the predicted values for IC was utilized, could be applied to identify the risk of PPS, we retrospectively analysed the cases of 412 patients who underwent thoracic surgery in Nagoya University Hospital. The multivariate analysis demonstrated that %IC predicted < 85% was one of the most critical risk predictors for PPS (odds ratio, 1.65; 95% confidence intervals, 1.03-2.648) and, in particular, was independent of percentage predicted forced expiratory volume in 1 s (%FEV1) < 80%. A combined assessment of ICFEV1 Low, defined as %IC predicted <85% or %FEV1 <80%, was able to identify more than double the number of patients with PPS, compared with %FEV1 <80% alone (65.9 vs. 28.5%, respectively). This is the first study to demonstrate the significance of %IC predicted in screening for the risk for PPS in patients undergoing thoracic surgery. PMID- 22307393 TI - An alternative method for neonatal cerebro-myocardial perfusion. AB - Several techniques have already been described for selective cerebral perfusion during repair of aortic arch pathology in children. One method combining cerebral with myocardial perfusion has also been proposed. A novel technique is reported here for selective and independent cerebro-myocardial perfusion for neonatal and infant arch surgery. Technical aspects and potential advantages are discussed. PMID- 22307394 TI - Optimal intraoperative anticoagulation strategy in patients undergoing off-pump coronary artery bypass. AB - A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was what the optimal intraoperative anticoagulation strategy should be in patients undergoing off-pump coronary artery bypass graft (CABG) surgery. A total of 157 papers were identified using the reported search, of which 8 were judged to represent the best evidence. The authors, journal, date, country of publication, study type, patient group studied, relevant outcomes and results were tabulated. The quality of clinical trials was assessed. Off-pump CABG is currently considered as a safe and effective alternative to CABG with the use of cardiopulmonary bypass, especially in the presence of off-pump expertise and certain pathologies. Although most technical steps in off-pump revascularization are standardized, it appears that there is inconsistency in intraoperative anticoagulation practice. Surveys conducted in the USA and Europe confirm the lack of uniform policy, with heparin dose ranging between 70 and 500 U/kg and from full-dose protamine to no reversal of anticoagulation. Although the quality of evidence is low, there is a trend for utilization of heparin at 150 U/kg, followed by half-dose protamine reversal, which appears to provide adequate anticoagulation for the safe conduct of anastomoses and thromboprophylaxis without significantly increasing the risk of postoperative bleeding. However, more research is necessary before firm recommendations can be made. PMID- 22307395 TI - Citrus aurantium L. exhibits apoptotic effects on U937 human leukemia cells partly through inhibition of Akt. AB - Citrus fruits have been used as edible fruits and a traditional medicine since ancient times. In particular, the peels of immature citrus fruits are frequently prescribed in concert with other support herbs for many types of disease including cancer. We investigated the anti-proliferative activity of the peels of Citrus aurantium L. along with their effects on apoptosis. We prepared crude methanol extracts of the peels of Citrus aurantium L. (CMEs) and performed experiments using U937 human leukemia cells. The growth of U937 cells was inhibited by CME treatment in a dose-dependent manner, and CME induced caspase dependent apoptosis. CME inhibited the expression of XIAP and Bcl-xL which are anti-apoptotic proteins. CME inhibited Akt activity in a dose-dependent manner. The apoptotic activity of CME was significantly attenuated by Akt augmentation. In conclusion, this study suggested that CME should induce caspase-dependent apoptosis at least in part through Akt inhibition, providing evidence that CMEs have anticancer activity on human leukemia cells. PMID- 22307397 TI - Transcriptional responses of cancer-related genes in turbot Scophthalmus maximus and mussels Mytilus edulis exposed to heavy fuel oil no. 6 and styrene. AB - Recent spills in European waters have released polycyclic aromatic hydrocarbons, important components of heavy fuel oil, and the hydrocarbon styrene. Heavy fuel oil and styrene are classified as potentially genotoxic and carcinogenic. Here we investigate transcription of genes involved in cancer development in the liver of juvenile turbots and in the digestive gland of mussels exposed to heavy fuel oil and to styrene and after a recovery period. In turbot, oil produced a significant up-regulation of p53 and gadd45alpha after 14 days exposure. cyclin G1 was up regulated after 7 days treatment with styrene. In mussels, ras was down-regulated in both treatments after the recovery periods. No mutations in ras hotspots were detected in exposed mussels. gadd45alpha was up-regulated after the recovery period of the styrene experiment. Overall, transcriptional responses differed in mussels compared to turbot. Turbot responded to hydrocarbon exposure by triggering cell cycle arrest (p53) and DNA repair (gadd45alpha). PMID- 22307399 TI - The molecular autopsy: should the evaluation continue after the funeral? AB - Sudden cardiac death (SCD) is one of the most common causes of death in developed countries, with most SCDs involving the elderly, and structural heart disease evident at autopsy. Each year, however, thousands of sudden deaths involving individuals younger than 35 years of age remain unexplained after a comprehensive medicolegal investigation that includes an autopsy. In fact, several epidemiologic studies have estimated that at least 3% and up to 53% of sudden deaths involving previously healthy children, adolescents, and young adults show no morphologic abnormalities identifiable at autopsy. Cardiac channelopathies associated with structurally normal hearts such as long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS) yield no evidence to be found at autopsy, leaving coroners, medical examiners, and forensic pathologists only to speculate that a lethal arrhythmia might lie at the heart of a sudden unexplained death (SUD). In cases of autopsy-negative SUD, continued investigation through either a cardiologic and genetic evaluation of first- or second-degree relatives or a molecular autopsy may elucidate the underlying mechanism contributing to the sudden death and allow for identification of living family members with the pathogenic substrate that renders them vulnerable, with an increased risk for cardiac events including syncope, cardiac arrest, and sudden death. PMID- 22307400 TI - The role of Shox2 in SAN development and function. AB - Embryonic development is a tightly regulated process, and many families of genes functions to provide a regulatory genetic network to achieve such a program. The homeobox genes are an extensive family that encodes transcription factors with a characteristic 60-amino acid homeodomain. Mutations in these genes or in the encoded proteins might result in structural malformations, physiological defects, and even embryonic death. Mutations in the short-stature homeobox gene (SHOX) is associated with idiopathic short stature in humans, as observed in patients with Turner syndrome and/or Leri-Weill dyschondrosteosis. A closely related human homolog, SHOX2, has not been linked to any syndrome or defect so far. In mice, a SHOX ortholog gene is not present in the genome; however, a true SHOX2 ortholog has been identified. Analyses of Shox2 knockout mouse models have showed crucial functions during embryonic development, including limb skeletogenesis, palatogenesis, temporomandibular joint formation, and cardiovascular development. During embryonic cardiac development, Shox2 is restrictedly expressed in the sinus venosus region, including the sinoatrial node (SAN) and the sinus valves. Shox2 null mutant is embryonically lethal due to cardiovascular defects, including a severely hypoplastic SAN and sinus valves attributed to a significantly decreased level of cell proliferation in addition to an abnormal low heartbeat rate (bradycardia). In addition, it has been demonstrated that Shox2 regulates a genetic network through the repression of Nkx2.5 to maintain the SAN fate and thus plays essential roles in its proper formation and differentiation. PMID- 22307401 TI - Improved closure of patent ductus arteriosus with high doses of ibuprofen. AB - The patent ductus arteriosus (PDA) is associated with various complications of prematurity. Cyclooxygenase-inhibitors are the first-line intervention for closure of the PDA. However, the rates of PDA closure still are unsatisfactory. Therefore, an individual trial was performed by changing the strategy for treating neonates with ibuprofen to induce the closure of PDA. In a retrospective study, patients receiving 20, 10, and 10 mg/kg bodyweight ibuprofen (group 1) were compared by chart review with those receiving 10, 5, 5 mg/kg (group 2). The rate of PDA closure, the incidence of side effects related to the use of ibuprofen, and the need for surgical intervention for closure of the PDA were analyzed. A higher rate of closure after three doses in group 1 could be observed (60.9 vs 52.6%; p = 0.75), which was not significant but indicated a clear positive trend. If closure of the PDA was unsuccessful, intravenous ibuprofen was continued for an additional 2 days. After 5 days, 91.3% of PDA in group 1 was closed compared with 68.4% PDA in group 2. In summary, only 8.7% of the group 1 neonates needed surgical closure of PDA after insufficient medicamentous closure compared with 31.6% in group 2 (p = 0.25). Although not statistically significant, a clear positive trend for using the higher-dose medication can be seen. More work dealing with the limitations of a retrospective study must be done. Based on the data from this study, high-dose ibuprofen seems able to increase the rate of effective medicamentous PDA closure without any further unwanted side effects. PMID- 22307402 TI - Portal venous gas: a clinical finding in obstructed infracardiac total anomalous pulmonary venous connection. AB - Total anomalous pulmonary venous connection is a cyanotic congenital heart defect that presents with a multitude of clinical presentations. We report a case of obstructive total anomalous pulmonary venous connection (TAPVC) which presented in a way that has not previously been described. An infant with mixed type obstructive TAPVC was found to have pulmonary interstitial emphysema and portal venous gas on a scout radiograph obtained prior to computed tomography scan. The presence of portal venous gas indicated a connection between the pulmonary venous system and the portal venous system infradiaphragmatically. PMID- 22307403 TI - Thermoelectric properties of nanocomposite thin films prepared with poly(3,4 ethylenedioxythiophene) poly(styrenesulfonate) and graphene. AB - Carbon nanotubes (CNTs), either single wall carbon nanotubes (SWNTs) or multiwall carbon nanotubes (MWNTs), can improve the thermoelectric properties of poly(3,4 ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT : PSS), but it requires addition of 30-40 wt% CNTs. We report that the figure of merit (ZT) value of PEDOT : PSS thin film for thermoelectric property is increased about 10 times by incorporating 2 wt% of graphene. PEDOT : PSS thin films containing 1, 2, 3 wt% graphene are prepared by solution spin coating method. X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy analyses identified the strong pi-pi interactions which facilitated the dispersion between graphene and PEDOT : PSS. The uniformly distributed graphene increased the interfacial area by 2-10 times as compared with CNT based on the same weight. The power factor and ZT value of PEDOT : PSS thin film containing 2 wt% graphene was 11.09 MUW mK(-2) and 2.1 * 10(-2), respectively. This enhancement arises from the facilitated carrier transfer between PEDOT : PSS and graphene as well as the high electron mobility of graphene (200,000 cm(2) V(-1) s(-1)). Furthermore the porous structure of the thin film decreases the thermal conductivity resulting in a high ZT value, which is higher by 20% than that for a PEDOT : PSS thin film containing 35 wt% SWNTs. PMID- 22307404 TI - miR-125b targets ARID3B in breast cancer cells. AB - Mounting evidence suggests involvement of deregulated microRNA (miRNA) expression during the complex events of tumorigenesis. Among such deregulated miRNAs in cancer, miR-125b expression is reported to be consistently low in breast cancers. In this study, we screened a panel of breast cancer cell lines (BCCLs) for miR 125b expression and detected decreased expression in 14 of 19 BCCLs. Due to the heterogeneity of breast cancers, MCF7 cells were chosen as a model system for ERBB2 independent breast cancers to restore miR-125b expression (MCF7-125b) to investigate the phenotypical and related functional changes. Earlier, miR-125b was shown to regulate cell motility by targeting ERBB2 in ERBB2 overexpressing breast cancer cells. Here we showed decreased motility and migration in miR-125b expressing MCF7 cells, independent of ERBB2. MCF7-125b cells demonstrated profoundly decreased cytoplasmic protrusions detected by phalloidin staining of filamentous actin along with decreased motility and migration behaviors detected by in vitro wound closure and transwell migration assays compared to empty vector transfected cells (MCF7-EV). Among possible numerous targets of miR-125b, we showed ARID3B (AT-rich interactive domain 3B) to be a novel target with roles in cell motility in breast cancer cells. When ARID3B was transiently silenced, the decreased cell migration was also observed. In light of these findings, miR-125b continues to emerge as an interesting regulator of cancer related phenotypes. PMID- 22307406 TI - The global role of kidney transplantation. AB - World Kidney Day on March 8, 2012, provides a chance to reflect on the success of kidney transplantation as a therapy for end-stage kidney disease, which surpasses dialysis treatments both for the quality and quantity of life it provides and for its cost effectiveness. Anything that is both cheaper and better but is not actually the dominant therapy, must have other drawbacks that prevent replacement of all dialysis treatment by transplantation. The barriers to universal transplantation as the therapy for end-stage kidney disease include the economic limitations, which in some countries, place transplantation, appropriately, at a lower priority than public health fundamentals such as clean water, sanitation and vaccination. Even in high-income countries, the technical challenges of surgery and the consequences of immunosuppression restrict the number of suitable recipients, but the major finite restrictions on kidney transplantation rates are the shortage of donated organs and the limited medical, surgical and nursing workforces with the required expertise. These problems have solutions which involve the full range of societal, professional, governmental and political environments. World Kidney Day is a call to deliver transplantation therapy to the 1 million people a year who have a right to benefit from it. PMID- 22307408 TI - Expression and distribution of creatine transporter and creatine kinase (brain isoform) in developing and mature rat cochlear tissues. AB - Physiological processes in the cochlea associated with sound transduction and maintenance of the unique electrochemical environment are metabolically demanding. Creatine maintains ATP homeostasis by providing high-energy phosphates for ATP regeneration which is catalyzed by creatine kinase (CK). Cellular uptake of creatine requires a specific high affinity sodium- and chloride-dependent creatine transporter (CRT). This study postulates that this CRT is developmentally regulated in the rat cochlea. CRT expression was measured by quantitative real-time RT-PCR and immunohistochemistry in the postnatal (P0-P14) and adult (P22-P56) rat cochlea. The maximum CRT expression was reached at the onset of hearing (P12), and this level was maintained through to adulthood. CRT immunoreactivity was strongest in the sensory inner hair cells, supporting cells and the spiral ganglion neurons. Cochlear distribution of the CK brain isoform (CKB) was also assessed by immunohistochemistry and compared with the distribution of CRT in the developing and adult cochlea. CKB was immunolocalized in the organ of Corti supporting cells, and the lateral wall tissues involved in K(+) cycling, including stria vascularis and spiral ligament fibrocytes. Similar to CRT, CKB reached peak expression after the onset of hearing. Differential spatial and temporal expression of CRT and CK in cochlear tissues during development may reflect differential requirements for creatine-phosphocreatine buffering to replenish ATP consumed during energy-dependent metabolic processes, especially around the period when the cochlea becomes responsive to airborne sound. PMID- 22307409 TI - Genetic variation in the epigenetic machinery and mental health. AB - DNA methylation and chromatin modifications regulate gene expression and contribute to changes in brain transcriptomes underlying neurodevelopmental and psychiatric disorders. Clinical genetics and preclinical animal models highlight the crucial importance of the correct establishment of epigenetic marks during sensitive windows of development for normal brain function. On the same side of the coin, some of the concerned factors also appear engaged in the programming of experience-dependent long-term effects on mental health following exposure to relevant early-life events. Delineating the particular role of genetic variations in these players could provide new insights into the molecular basis of vulnerability and resilience and advance tailored therapies. PMID- 22307410 TI - Sternal cleft: prenatal multimodality imaging. AB - Sternal clefts have been reported sporadically, but there are no reports describing complete investigations of the malformation. We describe a child with isolated inferior sternal cleft diagnosed at 33 weeks of gestation and thoroughly investigated by prenatal US, MRI and CT and preoperative US. Our report highlights the importance of accurate and in-depth investigation by multimodality imaging that allows detection of accompanying serious anomalies and, hence, forms the basis for informed parental counselling and for postnatal interdisciplinary care. PMID- 22307411 TI - [Special aspects of dermatologic surgery in children]. AB - This reviews gives suggestions how to meet the needs of our young patients, especially with reference to dermatologic surgery. With the right attitude, specific knowledge and appropriate preparation, a potential disruption can be transformed into a low-conflict routine or even a rewarding experience for all persons involved. PMID- 22307412 TI - Control of nitrogen insertion during the growth of nitrogen-containing carbon nanofibers on cordierite monolith walls. AB - A well attached coating of nitrogen-functionalised carbon nanofibers (N-CNFs) has been prepared on the walls of cordierite monolith channels. It is formed via concurrent decomposition of ethane and ammonia catalysed by nickel nanoparticles dispersed on alumina coated cordierite monolith. N-CNF/monoliths synthesis employing several growth temperatures and NH(3) compositions was exhaustively characterised by Raman, XPS, elemental analysis and TEM. Synthesis conditions affected profoundly content and type of nitrogen functionality, enabling its fine tuning. N-CNFs surface chemistry and microstructure differed remarkably from its N-free counterparts. PMID- 22307413 TI - [Commitment, will and respect for the values to enter a new century of the Sociedad Argentina de Pediatria]. PMID- 22307414 TI - [The other price of grants]. PMID- 22307415 TI - [Pediatric pharmacology and use of unapproved drugs (off label)]. PMID- 22307416 TI - [Multimedia courses]. PMID- 22307417 TI - [In-service training to improve quality of health care]. AB - Argentine's neonatal mortality rate represents 60% of infant mortality; implementation of strategies that improve quality of neonatal care is a priority. Traditionally, the training of health professionals is accomplished through scientific meetings with little capacity for exchange; in-service training incorporates the identification and resolution of problems joining the daily patient care. OBJECTIVE: To describe the in-service training program (ISTP), to identify its strengths as strategies for quality of care improvement and to evaluate its impact in four different Argentine maternity services. METHOD: DESIGN: health services research intervention study, not controlled, before and after evaluation. INTERVENTION: This program is a multidimensional strategy consisting in regular visits by a neonatologist and a nurse to health professionals in their own settings. Program stages: 1) service assessment and design of the action plan according to the priorities, 2) implementation, 3) consolidation and analysis through indicators. RESULTS: Greatest impact was found over equipment and human resources improvement; we also observed an improvement in management related aspects like organization and coordination of care. The reduction of preventable deaths varied between centers. CONCLUSIONS: The in service training program is an effective tool with measurable quantitative and qualitative results with positive impact on the quality of care. Conjunctural factors and political will were determinant on the program's success, as it is commonly seen in the implementation of strategies that involve changing established structures. PMID- 22307418 TI - [Impact on the direct medical cost related to the influenza virus during 2009 in children under 5 years compared to the period 2006-2008 in a pediatric hospital]. AB - INTRODUCTION: Epidemic outbreaks of influenza occur every year and healthcare systems must amplify their response in accordance with available medical resources. This situation generates cost increases. During the recent influenza A pandemic, costs were likely to have been greater than in previous years. OBJECTIVE: To estimate direct health costs of influenza-related illness during 2009 compared to costs expended in the previous 3-year period at Ricardo Gutierrez Children's Hospital, City of Buenos Aires, Argentina. MATERIALS AND METHODS: We conducted a cross-sectional epidemiological study with retrospective control group to estimate influenza-related costs for the years 2006 to 2009 using data from outpatient consultations and hospital admissions for Acute Respiratory Infections attributable to Influenza virus in children under 5 years old. Incremental costs were estimated for the year 2009 compared to average costs for the period 2006-2008. RESULTS: Total incremental cost of hospital admissions and outpatient consultations for influenza was US$ 91512 for the year 2009 compared to average cost for 2006-2008 period (incremental cost of US$ 147560 for hospital admissions and US$ -56048 for outpatient consultations). CONCLUSIONS: Influenza-related costs were greater in 2009 than in previous years due to higher number of hospital admissions attributable to influenza A H1N1. PMID- 22307419 TI - [Reference intervals for serum thyrotropin during the first 14 days of life]. AB - INTRODUCTION: Early detection of congenital hypothyroidism (CH) prevents impaired cognitive and motor development at problems. To increase the screening program specificity, we defined reference intervals for serum TSH in newborns between 2 and 14 days of life. PATIENTS AND METHODS: Newborn infants from our neonatal screening program between 2001 and 2007. Serum TSH was determined by electrochemiluminescence. There were excluded neonates who died before the first month of life or with less than 1500 grams at birth, samples with TSH <0,01 uU/ml., processed after 14 days of life and from other medical centers. Statistical tools: Student t-tests, measures of centrality and dispersion, and logarithmic transformations. RESULTS: Studied population: 6772 newborn infants out of 7869, 50.49% were males. The male/ female ratio was similar during the 14 days. The mean age at testing was 5.85 days (+/- 2.58), and the mean of TSH value was 4.42 uU/ml (+/- 4.17). Inverse relationship was found between age and TSH (mean TSH at days 2 and 14 was 5.82 uU/ ml and 2.58 respectively). CONCLUSION: We found statistical evidence on an inverse relationship between TSH and age in newborn infants with 14 days of age. Reference intervals for TSH contribute to a better assessment of thyroid status in neonates and to define an appropriate conduct for individual therapy. PMID- 22307420 TI - [Educating at today's society]. PMID- 22307421 TI - [Impact of climate change on infectious diseases]. AB - Infections in humans are related with changes in the environment specially those associated with food, water, and vectors. Changes in the environment are also related to epidemics, however this relationship has not been clarified, and multiple factors additional to climate changes may be involved in the pathogenesis of epidemics. Therefore, several predictive epidemiological models have been developed with the aim to determine the degree of sensitivity of different diseases to climate changes, and their association with outbreaks to plan prevention strategies. PMID- 22307422 TI - [Advantages and drawbacks of amphotericin formulations in children: literature review]. AB - Fungal infections have increased in morbidity, and the range of fungal species causing disease in humans has expanded, mainly due to the rise in number of immunocompromised patients. Amphotericin B is a broad spectrum antifungal agent that has been the standard therapy for many life-threatening mycoses for the past 50 years. However, the use of this drug is commonly associated with infusion related events (such as chills, fever, headache, nausea, vomiting), and most significantly to dose limiting nephrotoxicity. Three lipid formulations that increase the therapeutic index have been approved for use. However, questions regarding dose, cost-effectiveness and indications exist in the pediatric setting. Although no high quality evidence studies in children comparing the four types of amphotericin in culture-positive fungal infections currently exist, all four preparations are believed to have similar effectiveness. High drug costs limit the use of lipid formulations; however, renal toxic side effects should be taken into account when costs are considered. PMID- 22307423 TI - [Bronchiectasis in pediatrics, diagnosis approach and management]. AB - Bronchiectasis is still an important health problem in both, developed and developing countries. Cystic fibrosis is one of the most important causes, but a great variety of other causes makes non cystic fibrosis bronchiectasis a relatively frequent diagnosis. Early diagnosis based on medical history and radiological confirmation is only the starting point to determine the specific etiology, in order to establish a treatment focused on the underlying cause. For this purpose, an orderly and systematic diagnostic evaluation is required. A review article about bronchiectasis, particularly those not related to cystic fibrosis, is presented. PMID- 22307424 TI - [Renal functional reserve in children with a history of hemolytic uremic syndrome through technetium-99m diethylene-triamine-penta-acetic acid clearance]. AB - Protein loads in normal subjects increase glomerular filtration rate (GFR), which implies a renal functional reserve (RFR). Patients who have suffered a loss in the number of nephrons may show normal values of GFR due to hyperfiltration of remnant nephrons, with subsequent loss of RFR. This could be an early sign of renal damage, and probably a contributory factor to renal damage progress. The objective of this study is to determine the RFR through technetium-99m diethylene triamine-penta-acetic acid (99m Tc-DTPA) clearance in patients who have recovered from hemolytic uremic syndrome. Renal functional reserve was determined in 33 children from 2 to 16 years old, with normal values of proteinuria, serum creatinine and creatinine clearance after over a year of having suffered hemolitic uremic syndrome. For that purpose 99m Tc-DTPA clearance was determined in basal condition and following protein load. In 17 patients DTPA clearance increased 20% or more after protein load compared to basal condition, and they were considered to have normal RFR, a probably index of totally recovered renal function; in the remaining 16 patients the increases were lower than 20%, and were considered to have no RFR, condition that was postulated as a contributing factor to renal damage progress. There was not significant differences either in age or basal GFR between both groups. Being the test easier than inuline clearance and more accurate than creatinine clearance, it proves particularly useful for early diagnosis of patients that need special follow-up and treatment. PMID- 22307425 TI - [Air travel, risks and cautions to consider in children]. PMID- 22307426 TI - [Recommendations in Neonatal Resuscitation 2011: 3rd part: medication and volume expanders. Care after resuscitation. Ethical issues]. PMID- 22307427 TI - [Coarctation of the aorta]. PMID- 22307429 TI - [Cardiac tamponade as a complication of ventriculo atrial shunt]. AB - Cardiac tamponade is an uncommon disorder in pediatric patients. We report a case of cardiac tamponade secondary to accumulation of cerebrospinal fluid due to ventriculo-atrial derivation (VAD) disfunction. An 11-month-old girl was assisted because of respiratory distress and tachycardia, without fever. She had a ventriculoatrial derivation, because of hydro-cephalus since two month earlier. The echocardiogram showed a pericardial effusion and the distal VAD located inside the right cardiac ventricle. The distal VAD was retired and replaced between superior cava vein and right atrium. The patient recovered ad integrum without pericardial effusion. In cases of patients with VAD presenting a clinical disorder, it should be ruled out VAD dysfunction or inappropriate placement. PMID- 22307430 TI - [Lichen nitidus. Report of two cases, one of them with a generalized distribution]. AB - Lichen nitidus is a dermatosis of unknown origin, characterized by the presence of shiny, pinpoint, skin-colored papules that may be asymptomatic or slightly pruriginous. They usually affect forearms, abdomen, buttocks and genitals. We report two cases, one of them with a generalized presentation. Both were treated with topical steroids with good results. A review of this pathology and its therapeutic options is held. PMID- 22307431 TI - [Ovarian mucinous borderline cystoadenoma, in a premenarchal girl]. AB - Ovarian epithelial tumors (cystoadenomas/cystoadenocar-cinomas) are not as common in girls as the germinal tumors (teratomas). Mucinous or serous borderline cystoadenomas (CAdB) with a low malignant potencial, represent 20% of epithelial tumors. As an intermediate type of benign-malignant neoplasia, these tumors are usually giant cystic pelvic masses found in young females, but exceedingly rare before menarche. Stage 1 (tumor limited to the ovary) is the most frequent stage at diagnosis. Bilateral ovarian compromise occurs in 10-15% of patients. Open surgery is preferred to perform a fertility sparing procedure such as oophorectomy, salpingo-oophorectomy or even a tumorectomy in selected cases. The latter requires intraoperative biopsy confirmation of free margins, to prevent recurrence. Prolonged follow up is indicated to detect a recurrence or a contralateral tumor development. Survival is excellent in most of these patients. We present the case of a premenarchal girl with a huge mucinous CAdB. PMID- 22307432 TI - [Staphylococcus aureus methicillin-resistant community acquired neonatal orbital cellulitis]. AB - Orbital cellulitis typically occurs in older children, but it can occasionally affect infants and neonates. Staphylococcus aureus is the main pathogen isolated. Outcome depends on an adequate initial approach. We report three neonates with orbital cellulitis caused by community-associated MRSA. PMID- 22307433 TI - Infection control in healthcare settings in Japan. AB - In Japan, the practice of infection control in healthcare settings has a short history of less than 3 decades. Before that, infection control practices were far from perfect and even ignored. This review summarizes changes in infection control in Japan since the 1980s and offers some comparisons with practices in foreign countries, especially the United States. Infection control is far better now than 25 years ago, but there remain fundamental issues that limit the development of better infection control practices. These problems include insufficient funding and human resources due to the socialized healthcare insurance system in Japan and the lack of interest in infection control research. PMID- 22307434 TI - Epidemiology of Kawasaki disease in Asia, Europe, and the United States. AB - Kawasaki disease (KD) is a systemic vasculitis that mainly affects children younger than 5 years. Although Dr. Tomisaku Kawasaki first reported KD over 40 years ago, the cause of the disease remains unknown. Currently, KD has been diagnosed in more than 60 countries, including those in Asia, the Middle East, Latin America, and Africa, as well as in North America and Europe. The purpose of this review is to describe the epidemiologic features of KD--particularly its incidence, seasonality, and the occurrence of coronary artery abnormalities- primarily in Japan and the United States, but also in Europe and other Asian countries. PMID- 22307435 TI - Personalized peptide vaccination in patients with refractory non-small cell lung cancer. AB - Since the prognosis of non-small cell lung cancer (NSCLC) remains poor, the development of novel therapeutic approaches, including cancer vaccines, is highly desirable. In the current study, we conducted a phase II study of personalized peptide vaccination (PPV), in which a maximum of 4 peptides were selected based on pre-existing humoral immune responses and administered subcutaneously (weekly for 6 consecutive weeks and bi-weekly thereafter) in refractory NSCLC patients. Forty-one refractory NSCLC patients (4 stage IIIb, 22 stage IV and 15 recurrent), who had failed to respond to chemotherapy and/or targeted therapy (median number of regimens, 3; median duration, 10 months), were enrolled. Median overall survival (OS) was 304 days with a one-year survival rate of 42% in the enrolled patients. The main toxicity of PPV was skin reactions at the injection sites, but no serious adverse events were observed. In order to identify potential biomarkers for predicting OS, pre-vaccination and post-vaccination clinical findings and laboratory data were retrospectively assessed and evaluated by multivariate Cox regression analysis. Among the pre-vaccination factors examined, high C-reactive protein (CRP) level was a significant predictor of unfavorable OS [hazard ratio (HR)=10.115, 95% confidence interval (CI)=2.447-41.806, P=0.001]. Among the post-vaccination factors, high CRP level and low frequency of CD3+CD26+ cells were significant predictors of unfavorable OS (HR=23.127, 95% CI=2.919 183.233, P=0.003; HR=0.952, 95% CI=0.917-0.989, P=0.012). Taken together, our results suggest the feasibility of PPV for the treatment of refractory NSCLC. Evaluation of the identified factors before or at an early stage of vaccination could be potentially useful for selecting NSCLC patients who would likely have better prognosis following PPV. PMID- 22307436 TI - Hyponatremia: a problem-solving approach to clinical cases. AB - Hyponatremia, defined as a serum sodium concentration of <135 mmol/L, often develops as a consequence of elevated levels of arginine vasopressin (AVP) hormone. AVP elevation can occur in a number of common clinical conditions, including syndrome of inappropriate secretion of AVP, volume depletion, postoperative states, heart failure, cirrhosis, neuroendocrine disorders and trauma. A history of concurrent illness and medication use, assessment of extracellular fluid volume as well as measurement of serum and urine osmolality and urine sodium concentration will help to establish the primary underlying causes. Presence or absence of significant neurologic signs and symptoms must guide treatment. Symptomatic hyponatremia must be treated promptly with 3% hypertonic saline to increase the serum sodium by 1-2 mmol/L per hour until symptoms abate, or a total magnitude of correction of 12 mmol/L in 24 hours or 18 mmol/L in 48 hours is achieved. Initial infusion rate (ml/kg per hour) can be estimated by body weight (kg) x desired rate of increase in sodium (mmol/L per hour). An overly rapid increase in sodium (>12 mmol/L per 24 hours) may result in serious neurologic injury. Fluid restriction and loop diuretic are frequently employed to treat volume overload. Vasopressin receptor antagonists provide prompt and effective water diuresis and increase in serum sodium concentration in both euvolemic and hypervolemic hyponatremia. In this review article, the author introduces a problem-solving approach to dissect the different clinical cases with hyponatremia and presents simple algorithms for the evaluation and management of hyponatremia that are useful at the bedside to improve quality, safety and cost-effectiveness of the patient's care. PMID- 22307437 TI - Association between CTLA4 gene polymorphisms and acute rejection of kidney transplantation: a meta-analysis. AB - OBJECTIVE: Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) has been shown to transmit an inhibitory signal to T cells, which is a therapeutic target for acute rejection of kidney transplantation, and CTLA4 polymorphisms have also been considered as a potential risk factor. However, major studies have not yielded significant results. Thus, we conducted a meta-analysis of existing studies to boost their statistical power to clarify any associations between CTLA4 gene polymorphisms and acute rejection of kidney transplantation. METHODS: We searched for studies using PubMed, Embase and Academic Source Premier databases and checked the reference lists of all included studies for other relevant studies. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by both dominant and recessive genetic models. RESULTS: For CTLA4 +49A/G polymorphism, we found a marginally significant p value for A vs. G (OR=0.805, 95% CI, 0.677-0.957, p=0.014). No significant association between the -318C/T polymorphism and acute rejection risk was observed. CONCLUSION: The results suggest that the CTLA4 gene +49A/G polymorphism may be a possible genetic susceptibility locus for acute rejection. The results of the present meta analysis may be limited by a number of factors including inadequate total sample size and poor statistics, and should be interpreted with caution. Further confirmation in large and well-designed studies are needed. PMID- 22307438 TI - Insulin glargine improves glycemic control and quality of life in type 2 diabetic patients on hemodialysis. AB - BACKGROUND: Diabetic patients on hemodialysis often experience severe hypoglycemia during intensive insulin therapy using conventional neutral protamine hagedorn (NPH) or nonintensive therapy with premixed insulin. Insulin glargine can simulate normal basal insulin secretion. We investigated the efficacy and safety of switching from NPH to glargine in type 2 diabetes patients on hemodialysis. METHODS: Hemodialysis patients who were being treated with NPH based basal-bolus insulin therapy, regular insulin, NPH insulin or premixed insulin were switched to glargine. The target early morning fasting blood glucose (FBG) level was 110 mg/dL. Any increase in glargine dose was coupled with a reduction in the dose of any regular or rapid-acting insulin analogue as far as possible while maintaining a constant daily insulin dose. FBG, HbA(1c), daily insulin dosage, percentage of basal insulin dose in total daily insulin dose, body weight and incidence of hypoglycemic events were evaluated during the study period. Quality of life (QOL) was measured with a short questionnaire. RESULTS: HbA(1c) improved significantly during the observation period after switching. The daily insulin dose was reduced from 20.1 +/- 15.2 to 18.1 +/- 15.1 U/day, although the change was not statistically significant. FBG decreased significantly from 174.4 +/- 58.7 to 126.2 +/- 27.7 mg/dL. Body weight measured after dialysis did not change, and there were no changes in hemoglobin or hematocrit. The frequency of hypoglycemic episodes decreased significantly. QOL reports with switching to glargine were improved compared with those before switching. CONCLUSION: The results suggest that glargine is useful, can improve QOL of diabetic patients on hemodialysis, and achieve better glycemic control than NPH. PMID- 22307439 TI - The effect of different doses and types of intravenous iron on oxidative stress and inflammation in hemodialysis patients. AB - BACKGROUND: Although intravenous iron (IVI) is thought to have potential inflammatory and atherogenic effects, there are not enough studies comparing these effects in chronic hemodialysis (HD) patients. In this study, different doses and types of IVI were examined for effects on inflammation and oxidative stress. METHODS: Chronic HD patients (n=101) were grouped into those not receiving IVI (group 1, n=29), those getting intermittent iron sucrose (group 2, n=25), those receiving intermittent iron dextran (group 3, n=24) and those getting a once monthly total dose of iron dextran (group 4, n=23). Malondialdehyde (MDA), advanced oxidation protein product (AOPP), C-reactive protein (CRP) and TNF-alpha levels were measured on days 0, 2, 7 and 28. RESULTS: Groups were similar regarding age, sex, hemoglobin, iron indices and total amount of IVI given monthly. Although MDA levels at days 7 and 28, AOPP levels at days 0 and 28, CRP levels at day 28 and TNF-alpha level at day 7 were higher than at other days, there were no significant differences between the IVI groups on statistical analysis. CONCLUSION: The different types and doses (intermittent or once monthly total dose) of IVI treatments are well tolerated without negative effects on the markers of lipid and protein oxidation and inflammatory indices in chronic HD patients. PMID- 22307440 TI - Normal fractional urate excretion identifies hyponatremic patients with reset osmostat. AB - BACKGROUND: Reset osmostat (RO) occurs in 36% of patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and is not often considered when evaluating hyponatremic patients. Patients with RO are not usually treated, but recent awareness that symptoms are associated with mild hyponatremia creates a therapeutic dilemma. We encountered patients with hyponatremia, hypouricemia and high urine sodium concentration (UNa), who had normal fractional excretion (FE) of urate and excreted dilute urines that were consistent with RO. We decided to test whether a normal FEurate in nonedematous hyponatremia irrespective of UNa or serum urate would identify patients with RO. METHODS: We determined FEurate in nonedematous hyponatremic patients. A diagnosis of RO was made if urine osmolality (Uosm) was <200 mOsm/kg in a random urine. We performed a modified water-loading test in patients with a normal FEurate whose random Uosm was >200 mOsm/kg. RESULTS: All nonedematous hyponatremic patients with FEurate of 4%-11% had RO, as determined by Uosm <200 mOsm/kg on a random urine collection in 8 patients, or after a modified water-loading test in 6 patients. Plasma antidiuretic hormone (ADH) in 4 patients was undetectable at <1 pg/mL during water-loading. Nine patients had baseline concentrated urine, 12 had UNa >20 mmol/L, 9 were hypouricemic, yet all had a normal FEurate. Comorbidities were similar to those reported in RO. CONCLUSIONS: RO, a benign form of SIADH, occurs commonly. A normal FEurate in a nonedematous hyponatremic patient is highly suggestive of RO. Determining FEurate is superior to serum urate. The therapeutic dilemma for RO must be resolved. PMID- 22307441 TI - Creatinine clearance, cystatin C, beta2-microglobulin and TATI as markers of renal function in patients with proteinuria. AB - BACKGROUND: Proteinuria is a risk factor for end-stage renal disease (ESRD). Creatinine clearance (CrCl) is usually used as a marker to monitor the progression of ESRD, while cystatin C (CYST) has also been considered as a marker of renal function. Tumor-associated trypsin inhibitor (TATI) has been shown to be a promising marker of renal function. The aim of this study was to examine the relationship between CrCl, CYST, beta(2)-microglobulin (B2M) and TATI, with glomerular filtration rate (GFR) in patients with different levels of proteinuria. METHODS: Seventy-one patients (37 males, 34 females, mean age 53 +/- 15 years) were included in the study. GFR was measured by the bladder cumulative method using (99m)Tc-DTPA. Blood levels of CYST, B2M and TATI were also measured. CrCl and proteinuria were determined by 24-hour urine collection. Statistical analysis was performed with multivariate analysis. RESULTS: The results are expressed as the ratio to GFR of CrCl and reciprocals of CYST (100/CYST), B2M (100/B2M) and TATI (100/TATI). The ratio CrCl/GFR increased from 1.41 in patients with proteinuria <1 g/day, to 1.66 (p<0.05) in those with proteinuria >3 g/day. The ratio 100/CYST/GFR was 1.67 and 2.28 (p<0.05), 100/B2M/GFR 0.90 and 0.69 and 100/TATI/GFR 0.14 and 0.19, respectively. Multivariate analysis demonstrated that ClCr/GFR as well as 100/CYST/GFR was independently related to the degree of proteinuria. CONCLUSIONS: CrCl and CYST overestimate GFR in patients with heavy proteinuria, while the ratios 100/TATI and 100/B2M with GFR do not significantly change. The direct measurement of GFR still remains the best method to assess the progression of renal damage in patients with heavy proteinuria. PMID- 22307442 TI - A novel GLA mutation in a Fabry family with glucose-6-phosphate dehydrogenase deficiency. AB - Fabry disease is an X-linked lysosomal disease caused by mutations of the alpha galactosidase A (GLA) gene at chromosome subband Xq22.1. To date, more than 600 genetic mutations have been identified to determine the nature and frequency of the molecular lesions causing the classical and milder variant phenotypes and for precise carrier detection. We report here a Fabry family (mother, son and daughter) where the alpha-galactosidase A defect was associated with a glucose-6 phosphate dehydrogenase (G6PD) deficiency. Mutation analysis revealed for the GLA gene the presence of a new mutation, i.e., a small deletion (c.452delA) on exon 3 and for the G6PD gene the presence of 2 mutations, p.V68M (G6PD Asahi, G6PD A+) and p.N126D (G6PD A+) on exon 3 and exon 4, respectively. PMID- 22307443 TI - Patterns of adolescents' beliefs about fighting and their relation to behavior and risk factors for aggression. AB - This study examined adolescents' patterns of beliefs about aggression, and how these patterns relate to aggressive and prosocial behavior, and to risk factors associated with aggression. A sample of 477 sixth graders from two urban schools and a school in a nearby county completed measures of beliefs, behavior, and individual, peer and parental factors associated with aggression. Teacher ratings of participants' behavior and emotion regulation were also obtained. The urban sample was 84% African American; the county school was in a rural fringe area with a student population that was 45% Caucasian and 40% African American. Latent class analysis of items on a beliefs measure supported hypotheses predicting three groups: (a) a Beliefs Against Fighting (BAGF) group that opposed the use of aggression (31% of the sample); (b) a Fighting is Sometimes Necessary (FSNEC) group that endorsed beliefs that fighting is sometimes necessary or inevitable (41%), and (c) a Beliefs Supporting Fighting (BSUPF) group that supported aggression across multiple contexts (28%). Differences across groups were found on race/ethnicity and family structure, but not on gender. Significant differences were also found such that the FSNEC group fell between levels of the BAGF and BSUPF groups on most measures. In contrast, the FSNEC and BAGF groups both differed from the BSUPF group, but not from each other on measures of empathy, perceived effectiveness of nonviolence and aggression, and parental messages supporting nonviolence. These differences suggest the need for tailoring prevention approaches for subgroups of adolescents who differ in their patterns of beliefs. PMID- 22307444 TI - Linguistic, psychometric validation and diagnostic ability assessment of an Italian version of a 19-item wearing-off questionnaire for wearing-off detection in Parkinson's disease. AB - A patient self-rated 19-item wearing-off questionnaire (WOQ-19) was shown to be a potent screening tool for wearing-off (WO) in patients with Parkinson's disease. As part of the early detection of wearing-off in Parkinson's disease study, we preliminarily performed a linguistic and a psychometric validation of an Italian version of the WOQ-19. Moreover, we assessed the sensitivity and specificity of the WOQ-19 in the office-based settings. The psychometric validation study included assessment of discriminant ability, internal consistency and test-retest reliability. The intraclass correlation coefficient (ICC) and the Cronbach's Alpha were assessed. The WOQ-19 sensitivity and specificity were calculated in respect to the physician assessment of WO, taken as the gold standard. The Italian version of WOQ-19 was found easy to understand by >= 80% of the patients. The number of WO-related symptoms detected by WOQ-19 was 7.5 +/- 3.2 in patients with WO and 1.6 +/- 2.6 in patients without WO (p < 0.0001). Cronbach's alpha was equal to 0.868 for the total number of WO symptoms. The ICC value was equal to 0.858 for WO-related symptoms as a whole. The diagnostic ability study recruited 207 patients: for a WOQ-19 cut-off >= 2, the sensitivity was equal to 0.881 and the specificity was 0.674. This is the first validation of WOQ-19 in Italian, with excellent linguistic validity and psychometric properties. WOQ-19 was confirmed to be reliable in WO detection. PMID- 22307445 TI - Economy class stroke syndromes and vertebral artery dissection. PMID- 22307446 TI - Wernekink commissure syndrome: a rare midbrain syndrome. AB - Wernekink commissure syndrome is a rare midbrain syndrome, which selectively destroys the Wernekink commissure involving the decussation of superior cerebellar peduncle in midbrain. This syndrome may display a clinical picture: bilateral cerebellar ataxia, eye movement disorders, and palatal tremor. We present two cases of the Wernekink commissure syndrome with acute onset of bilateral cerebellar dysfunction confirmed by magnetic resonance imaging. One patient presented internuclear ophthalmoplegia, but neither showed palatal tremor. It is notable that the bilateral cerebellar dysfunction may be ascribed to midbrain lesion involving the Wernekink commissure, and it may be the sole manifestation of the midbrain lesion. PMID- 22307447 TI - Critical illness polyneuropathy and myopathy are common neuromuscular complications secondary to sepsis. PMID- 22307449 TI - Speckle tracking analysis of the left ventricular anterior wall shows significantly decreased relative radial strain patterns in dystrophin deficient mice after 9 months of age. AB - BACKGROUND: Duchenne muscular dystrophy (DMD) is an inherited X-linked disorder with an incidence of 1 in 3,500 male births. Early treatment of DMD cardiomyopathy is under investigation and echocardiographic analysis of strain patterns may provide measures to better quantify early treatment outcomes. METHODS: We compared cardiac function in 3, 9 and 12 month old dystrophin deficient mdx mice to wild type (C57BL10/J) using in vivo high frequency echocardiography (Vevo 770, VisualSonics, Inc., Toronto, CA) and 2D speckle tracking [Velocity Vector Imaging (VVI), Siemens Medical Solutions, Inc., Malvern, PA]. Mice were anesthetized with 1-2% inhaled isoflurane and images were obtained using a 30 MHz transducer in modified parasternal long and short axis views obtained at the level of the papillary muscles. Myocardial motion was analyzed using VVI in single-beat reconstructed images. RESULTS: M-mode imaging showed significantly decreased shortening fraction in mdx mice compared to wild type at 12 months of age (SF% 26.6+/-3 vs. 32.2+/-2; p=0.002). Mdx mice showed significantly increased cardiac fibrosis at 12 months of age compared to controls (p<0.0001). Speckle tracking analysis of the left anterior mid ventricular wall segment showed significantly decreased relative radial strain in mdx mice at 9 and 12 months (4.5+/-1.3% vs. 8.4+/-0.7%; p=0.001). There were no significant differences in circumferential or longitudinal strain. CONCLUSION: Mdx mice show significantly decreased LV anterior mid wall radial strain with mild cardiomyopathy after 9 months of age compared to wild type. Speckle tracking analysis may provide novel outcome measures for preclinical cardiac drug treatment studies in DMD. PMID- 22307450 TI - Treatment options for tauopathies. AB - OPINION STATEMENT: To date, there are no approved and established pharmacologic treatment options for tauopathies, a very heterogenous group of neuropsychiatric diseases often leading to dementia and clinically diagnosed as atypical Parkinson syndromes. Among these so-called Parkinson plus syndromes are progressive supranuclear palsy (PSP), also referred to as Steele-Richardson-Olszewski syndrome; frontotemporal dementia (FTD); and corticobasal degeneration (CBD). Available treatment strategies are based mainly on small clinical trials, miscellaneous case reports, or small case-controlled studies. The results of these studies and conclusions about the efficacy of the medication used are often contradictory. Approved therapeutic agents for Alzheimer's dementia, such as acetylcholinesterase inhibitors and memantine, have been used off-label to treat cognitive and behavioral symptoms in tauopathies, but the outcome has not been consistent. Therapeutic agents for the symptomatic treatment of Parkinson's disease (levodopa or dopamine agonists) are used for motor symptoms in tauopathies. For behavioral or psychopathological symptoms, treatment with antidepressants-especially selective serotonin reuptake inhibitors-could be helpful. Antipsychotics are often not well tolerated because of their adverse effects, which are pronounced in tauopathies; these drugs should be given very carefully because of an increased risk of cerebrovascular events. In addition to pharmacologic options, physical, occupational, or speech therapy can be applied to improve functional abilities. Each pharmacologic or nonpharmacologic intervention should be fitted to the specific symptoms of the individual patient, and decisions about the type and duration of treatment should be based on its efficacy for the individual and the patient's tolerance. Currently, no effective treatment is available that targets the cause of these diseases. Current research focuses on targeting tau protein pathology, including pathologic aggregation or phosphorylation; these approaches seem to be very promising. PMID- 22307451 TI - The statistics of protein expression ratios for cellular fluorescence studies. AB - Fluorescence studies of cellular protein-protein interactions commonly employ transient cotransfection to express two proteins carrying distinct fluorescent labels. Because transiently transfected cells differ significantly in their expression level, the concentration ratio of the two expressed proteins varies, which in turn influences the measured fluorescence signal. Knowledge of the statistics of protein expression ratios is of considerable interest both from a fundamental point of view and for cellular fluorescence studies. Despite the perceived randomness of transient transfection, we were able to develop a quantitative model that describes the average and distribution of the protein expression ratio from a cell population. We show that the expression ratio is proportional to the molar plasmid ratio and relate the distribution to the finite number of active plasmids in the cell. The process of cationic lipid-mediated transfection is explored in more detail. Specifically, the influence of lipoplexes on the statistics of the expression ratio is examined. We further demonstrate that the transfection model provides a quantitative description of fluorescence fluctuation experiments, where only a fraction of the proteins are labeled. PMID- 22307452 TI - Thermal activated energy transfer between luminescent states of Mn2+-doped ZnTe nanoparticles embedded in a glass matrix. AB - Zn(1-x)Mn(x)Te nanocrystals (NCs), at various concentrations x, were successfully grown in a host glass matrix by the fusion method after appropriate annealing. Growth of these NCs was evidenced by optical absorption (OA), X-Ray Diffraction (XRD), magnetic force microscopy (MFM) and photoluminescence (PL) measurements. From the room temperature OA spectra, it was possible to observe the formation of two well defined, different sized groups of NCs, one attributed to quantum dots (QDs) and the other to bulk-like nanocrystals (NCs). XRD results have confirmed that the cubic zincblend structure of nanoparticles is not altered by the substitutional incorporation of Mn(2+) ions into the ZnTe NCs. MFM images supported the OA spectra results and thus provided additional confirmation of the formation of Zn(1-x)Mn(x)Te magnetic nanoparticles in the host glass matrix. The two groups of NCs were also observed in the PL spectra as well as deep defects attributed to the presence of oxygen centers in the electronic structure of the Zn(1-x)Mn(x)Te NCs. Strong agreement between the fitting model, based on rate equation, and experimental PL intensity data at different temperatures demonstrates that this model adequately describes the energy transfer processes between the NCs and the defects of the Zn(1-x)Mn(x)Te system at different temperatures. PMID- 22307454 TI - The effects of low back pain on natural breath control during a lowering task. AB - Preventative and rehabilitative efforts relative to low back pain (LBP) and manual material handling (MMH) are often directed toward proper technique. However, breath control may be an additional factor to consider. Optimizing breath control may provide increased segmental control of the spine through the production of increased intra-abdominal pressure. It has been found that breath control differs during the lifting phase of MMH for individuals with LBP. However, little is known about breath control during the lowering portion even though it accounts for 30% of MMH tasks. In this study, individuals with LBP (n = 32) and aged-matched healthy individuals (n = 30) lowered a crate from a table to the floor four times with the crate empty and four times with the crate loaded at 25% of body weight. The amount of volume in the lungs as a percentage of each individual's vital capacity (VC) was identified at nine points during the lowering task. Individuals with LBP completed the lowering task with significantly more volume in their lungs (45.9% VC) than healthy peers (40.9% VC). Further, with increasing age %VC significantly increased in those with LBP. Moreover, %VC significantly increased in response to the mechanical challenges introduced when lowering a load. These findings support the theoretical link between breath control and lumbar segmental control and provide preliminary evidence supporting rehabilitative efforts which add a focus on breath control for those with LBP. PMID- 22307456 TI - An expedient Pd/DBU mediated cyanation of aryl/heteroaryl bromides with K4[Fe(CN)6]. AB - A practical Pd(PPh(3))(4)/DBU catalytic system for the synthesis of pharmaceutically relevant aminopyridine nitrile intermediates, as well as a variety of other aryl nitriles using non-toxic K(4)[Fe(CN)(6)] has been developed. The key features of our new protocol for cyanation lie in that the reaction can be carried out with readily available Pd(PPh(3))(4) under mild and green conditions, even without the assistance of other ligands. PMID- 22307455 TI - Remarkable inhibition of mTOR signaling by the combination of rapamycin and 1,4 phenylenebis(methylene)selenocyanate in human prostate cancer cells. AB - Preclinical studies and clinical analyses have implicated the mammalian target of rapamycin (mTOR) pathway in the progression of prostate cancer, suggesting mTOR as a potential target for new therapies. mTOR, a serine/threonine kinase, belongs to two distinct signaling complexes: mTORC1 and mTORC2. We previously showed that the synthetic organoselenium compound, p-XSC, effectively inhibits viability and critical signaling molecules (e.g., androgen receptor, Akt) in androgen responsive (AR) and androgen independent (AI) human prostate cancer cells. On the basis of its inhibition of Akt, we hypothesized that p-XSC modulates mTORC2, an upstream regulator of the kinase. We further hypothesized that combining p-XSC with rapamycin, an mTORC1 inhibitor, would be an effective combinatory strategy for the inhibition of prostate cancer. The effects of p-XSC and rapamycin, alone or in combination, on viability and mTOR signaling were examined in AR LNCaP prostate cancer cells and AI C4-2 and DU145 cells. Phosphorylation of downstream targets of mTORC1 and mTORC2 was analyzed by immunoblotting. The interaction of mTORC1- and mTORC2-specific proteins with mTOR was probed through immunoprecipitation and immunoblotting. p-XSC inhibited phosphorylation of mTORC2 downstream targets, Akt and PCKalpha, and decreased the levels of rictor, an mTORC2-specific protein, coimmunoprecipitated with mTOR in C4-2 cells. The combination of p-XSC and rapamycin more effectively inhibited viability and mTOR signaling in C4-2, LNCaP and DU145 cells than either agent individually. PMID- 22307458 TI - Angiotensin-converting enzyme inhibitory and antioxidative activities and functional characterization of protein hydrolysates of hard-to-cook chickpeas. AB - BACKGROUND: The potential use of hard-to-cook (hardened) chickpeas to obtain value-added functional food ingredients was evaluated. For that purpose, some nutraceutical and functional attributes of several chickpea protein hydrolysates (CPHs) prepared from both fresh and hard-to-cook grains were evaluated. RESULTS: All the CPHs prepared from both fresh and hard-to-cook grains, with the enzymes alcalase, pancreatin and papain, showed high angiotensin converting enzyme inhibitory (ACE-I) activity with IC50 values ranging from 0.101 to 37.33 ug mL-1; similarly, high levels of antioxidant activity (around 18.17-95.61 umol Trolox equivalent antioxidant capacity ug-1 CPH) were obtained through both the 2,2 diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) methods. Regarding functional characterization of the CPHs, oil absorption values ranged from 1.91 to 2.20 mL oil g-1 CPH, with water solubility almost 100% from pH 7 to 10. CONCLUSION: The high antioxidant and ACE-I activities as well as the good functional properties of the CPH prepared from both fresh and hard-to cook grains, suggest its use in food formulations with value added in human health. PMID- 22307459 TI - Uncovering spatial topology represented by rat hippocampal population neuronal codes. AB - Hippocampal population codes play an important role in representation of spatial environment and spatial navigation. Uncovering the internal representation of hippocampal population codes will help understand neural mechanisms of the hippocampus. For instance, uncovering the patterns represented by rat hippocampus (CA1) pyramidal cells during periods of either navigation or sleep has been an active research topic over the past decades. However, previous approaches to analyze or decode firing patterns of population neurons all assume the knowledge of the place fields, which are estimated from training data a priori. The question still remains unclear how can we extract information from population neuronal responses either without a priori knowledge or in the presence of finite sampling constraint. Finding the answer to this question would leverage our ability to examine the population neuronal codes under different experimental conditions. Using rat hippocampus as a model system, we attempt to uncover the hidden "spatial topology" represented by the hippocampal population codes. We develop a hidden Markov model (HMM) and a variational Bayesian (VB) inference algorithm to achieve this computational goal, and we apply the analysis to extensive simulation and experimental data. Our empirical results show promising direction for discovering structural patterns of ensemble spike activity during periods of active navigation. This study would also provide useful insights for future exploratory data analysis of population neuronal codes during periods of sleep. PMID- 22307460 TI - Cardiomyocyte-expressed farnesoid-X-receptor is a novel apoptosis mediator and contributes to myocardial ischaemia/reperfusion injury. AB - AIMS: Emerging evidence indicates that nuclear receptors play a critical regulatory role in cardiovascular physiology/pathology. Recently, farnesoid-X receptor (FXR), a member of the metabolic nuclear receptor superfamily, has been demonstrated to be expressed in vascular cells, with important roles in vascular physiology/pathology. However, the potential cardiac function of FXR remains unclear. We investigated the cardiac expression and biological function of FXR. METHODS AND RESULTS: Farnesoid-X-receptor was detected in both isolated neonatal rat cardiac myocytes and fibroblasts. Natural and synthetic FXR agonists upregulated cardiac FXR expression, stimulated myocyte apoptosis, and reduced myocyte viability dose- and time-dependently. Mechanistic studies demonstrated that FXR agonists disrupted mitochondria, characterized by mitochondrial permeability transition pores activation, mitochondrial potential dissipation, cytochrome c release, and both caspase-9 and -3 activation. Such mitochondrial apoptotic responses were abolished by siRNA-mediated silencing of endogenous FXR or pharmacological inhibition of mitochondrial death signalling. Furthermore, low levels of FXR were detected in the adult mouse heart, with significant (~2.0 fold) upregulation after myocardial ischaemia/reperfusion (MI/R). Pharmacological inhibition or genetic ablation of FXR significantly reduced myocardial apoptosis by 29.0-53.4%, decreased infarct size by 23.4-49.7%, and improved cardiac function in ischaemic/reperfused myocardium. CONCLUSION: These results demonstrate that nuclear receptor FXR acts as a novel functional receptor in cardiac tissue, regulates apoptosis in cardiomyocytes, and contributes to MI/R injury. PMID- 22307461 TI - Circulating microparticles as indicators of peripartum cardiomyopathy. AB - AIMS: Peripartum cardiomyopathy (PPCM) is associated with high mortality and morbidity. Endothelial damage involving cathepsin-D to form a 16 kDa prolactin (PRL) peptide is pathogenetically relevant. Inhibiting PRL peptide with bromocriptine has yielded promising results. We investigated whether microparticles (MPs) can be quantified in serum as markers for diagnosis and treatment effects in PPCM. METHODS AND RESULTS: Patients with PPCM were compared with age-matched healthy post-partum women (PPCTR), healthy pregnant women (PCTR), healthy non-pregnant women (NPCTR), patients with ischaemic cardiomyopathy (ICM), patients with stable coronary artery disease (CAD) and healthy controls (HCTR). Peripartum cardiomyopathy treated with bromocriptine (PPCM-BR) and with PPCM without bromocriptine-treatment as control (PPCM-BRCTR) were compared. Microparticles were determined by flow cytometry. Endothelial MPs (EMPs) were elevated in PPCM compared with PPCTR, PCTR, and NPCTR, each P< 0.001. They were significantly elevated compared with ICM, CAD, and HCTR (P< 0.001). Pregnancy (PCTR) exhibited only slight increases vs. ICM, CAD, NPCTR, and HCTR. The increase in PPCM was due to an increase of activated but not apoptotic EMPs. Platelet-derived microparticles were highly increased in PPCM compared with ICM (P< 0.001) but 9.3 +/- 4.4-fold compared with CAD (P< 0.001). In NPCTR (P< 0.001) compared with NPCTR, the increase was 5.9 +/- 1.7-fold (P< 0.001). Microparticles generated from monocytes (MMPs) were increased 2.4 +/- 1.8-fold in PPCM compared with PCTR (P< 0.001) and 4.8 +/- 3.6-fold compared with CAD (P< 0.001), whereas leucocyte MPs (LMPs) were not significantly elevated. Endothelial microparticles were significantly reduced in PPCM treated additionally with bromocriptine compared with PPCM treated only with heart failure therapy (P< 0.001). CONCLUSION: Microparticle profiles may in long-term distinguish PPCM from normal pregnancy, heart failure, and vascular diseases and might be a diagnostic marker related to the pathomechanism of PPCM. PMID- 22307462 TI - Effect of statins on ventricular tachyarrhythmia, cardiac arrest, and sudden cardiac death: a meta-analysis of published and unpublished evidence from randomized trials. AB - AIMS: The effect of statin treatment on ventricular arrhythmic complications is uncertain. We sought to test whether statins reduce the risk of ventricular tachyarrhythmia, cardiac arrest, and sudden cardiac death. METHODS AND RESULTS: We searched MEDLINE, EMBASE, and CENTRAL up to October 2010. Randomized controlled trials comparing statin with no statin or comparing intensive vs. standard dose statin, with more than 100 participants and at least 6-month follow up were considered for inclusion and relevant unpublished data obtained from the investigators. Twenty-nine trials of statin vs. control (113 568 participants) were included in the main analyses. In these trials, statin therapy did not significantly reduce the risk of ventricular tachyarrhythmia [212 vs. 209; odds ratio (OR) = 1.02, 95% confidence interval (CI) 0.84-1.25, P = 0.87] or of cardiac arrest (82 vs. 78; OR = 1.05, 95% CI 0.76-1.45, P = 0.84), but was associated with a significant 10% reduction in sudden cardiac death (1131 vs. 1252; OR = 0.90; 95% CI 0.82-0.97, P = 0.01). This compared with a 22% reduction in the risk of other 'non-sudden' (mostly atherosclerotic) cardiac deaths (1235 vs. 1553; OR = 0.78, 95% CI 0.71-0.87, P < 0.001). Results were not materially altered by inclusion of eight trials (involving 41 452 participants) of intensive vs. standard dose statin regimens. CONCLUSION: Statins have a modest beneficial effect on sudden cardiac death. However, previous suggestions of a substantial protective effect on ventricular arrhythmic events could not be supported. PMID- 22307463 TI - Isolation of two novel marine ethylene-assimilating bacteria, Haliea species ETY M and ETY-NAG, containing particulate methane monooxygenase-like genes. AB - Two novel ethylene-assimilating bacteria, strains ETY-M and ETY-NAG, were isolated from seawater around Japan. The characteristics of both strains were investigated, and phylogenetic analyses of their 16S rRNA gene sequences showed that they belonged to the genus Haliea. In C1-4 gaseous hydrocarbons, both strains grew only on ethylene, but degraded ethane, propylene, and propane in addition to ethylene. Methane, n-butane, and i-butane were not utilized or degraded by either strain. Soluble methane monooxygenase-type genes, which are ubiquitous in alkene-assimilating bacteria for initial oxidation of alkenes, were not detected in these strains, although genes similar to particulate methane monooxygenases (pMMO)/ammonia monooxygenases (AMO) were observed. The phylogenetic tree of the deduced amino acid sequences formed a new clade near the monooxygenases of ethane-assimilating bacteria similar to other clades of pMMOs in type I, type II, and Verrucomicrobia methanotrophs and AMOs in alpha and beta proteobacteria. PMID- 22307465 TI - A novel CD44v6 targeting antibody fragment with improved tumor-to-blood ratio. AB - The chimeric monoclonal antibody U36 (cMAb U36) recognizes the CD44v6 antigen. Its potential as a radioimmunotargeting agent, as well as its safety, has been shown in previous studies in head and neck cancer patients. However, intact MAbs have long circulation time in the blood and tumor targeting may also be hampered due to the slow and incomplete diffusion into solid tumors. In comparison, smaller monovalent Fab' and divalent F(ab')2 fragments are expected to exhibit shorter circulating half-lives, better tumor penetration and are thus more likely to yield better imaging results. In this study, novel F(ab')2 and Fab' fragments from cMAb U36 were radiolabeled with 125I and the characteristics of the conjugates in vitro were examined. The biodistribution of the conjugates were then evaluated in nude mice bearing CD44v6-expressing xenograft tumors. Furthermore, the penetration depth and distribution in tumor tissue was assessed by autoradiography in selected tumor samples. The in vitro experiments showed that the conjugates were stable and had intact affinity to CD44v6. The biodistribution study demonstrated superior tumor-to-blood ratio for the novel cMAb U36 fragment 125I-F(ab')2 compared with both the intact MAb and the monovalent fragment form. Autoradiography also revealed better tumor penetration for 125I-F(ab')2. This study demonstrates that the use of antibody fragments may improve radioimmunotargeting and possibly improve the management of head and neck malignancies. PMID- 22307466 TI - Cerebral air embolism after central dialysis line removal: the role of the fibrin sheath as portal (mechanism) of air entry. AB - We report a case of cerebral air embolism after central dialysis line removal and the role of the fibrin sheath as portal (mechanism) of air entry. This case has been documented with computed tomographic (CT) images of the partially air-filled sheath tract. PMID- 22307467 TI - The effect of new clinical pathways on the outcome of vascular access surgery. AB - PURPOSE: Prior to 2007, the waiting time for vascular access surgery at our center was approximately 107 days compared to a UK average of 45 days. Two new pathways were developed; the rapid and super-rapid pathways incorporating an access liaison nurse who organized vessel mapping and referred patients for surgery. This audit was to determine whether the pathways were effective in reducing the waiting times and improving vascular accesses outcomes. METHODS: All 210 patients with established renal failure undergoing 232 vascular access procedures between January 2008 and March 2011 were studied. Detailed patient information including type of procedure and cause of access failure were stored in an Excel spreadsheet and analyzed using SPSS for Windows. RESULTS: One hundred and twenty patients had a brachiocephalic fistula, 61 a radiocephalic fistula, 39 an access using the basilic vein +/- transposition, and 11 a transposition of the long saphenous vein and one a brachio-axillary graft. Overall median waiting time from referral to access surgery was 23 days. Patients were followed up for a median of 248 days after surgery. The overall primary failure rate was 9.1% and 25 of 27 accesses failed because of thrombosis. The overall cumulative survival probability of accesses at one year was 61.4% with a mean survival of 621.2 days (SEM = 34.8). CONCLUSION: The clinical pathways have improved VA service to patients with a drastic reduction in waiting times, elimination of synthetic access, and maintenance of satisfactory results. PMID- 22307468 TI - Indications for vascular grafts as hemodialysis access: consensus from experience in Italy. AB - INTRODUCTION: In Italy, the use of arteriovenous grafts (AVG) is limited (1-5 %) due to different approaches to vascular access (VA) management as compared to other countries, where guidelines (which may not apply to the Italian setting) have been produced. Therefore, the Study Group (GdS) on VA of the Italian Society of Nephrology produced this position paper, providing a list of 8 recommendations built upon current guidelines. METHODS: The most controversial and innovative issues of existing guidelines have been summed up in 12 different statements. We selected 60 Italian dialysis graft experts, nephrologists and vascular surgeons (PP1SIN Study Investigators). They were asked to express their agreement/disagreement on each issue, thus creating a new method to share and exchange information. RESULTS: Most of them agreed (consensus > 90%) on specific criteria set to choose AVG over native AVF (nAVF) and tunnelled venous catheter (tVC) and on the necessary conditions to implant them. They did not fully agree on the use of AVG in obese patients, in patients at risk of developing ischemia, on the priority of AVG as an alternative to brachial-basilic fistula with vein transposition, and in case of a poorly organized setting regarding graft maintenance. Keeping in mind that the nAVF should be preferred whenever is feasible, AVGs are indicated when superficial veins are unavailable or to repair a nAVF (bridge graft). An AVG is an alternative to tVC if the expected patient survival is long enough to guarantee its clinical benefits. PMID- 22307469 TI - Common and uncommon complications of totally implantable central venous ports: a pictorial essay. AB - PURPOSE: The purpose of this study is to present the characteristic radiologic features of common and uncommon complications in totally implantable central venous ports. MATERIAL AND METHODS: The authors reviewed 138 implantations of central venous ports in oncologic patients during an 18-month period and present the characteristic imaging features of the complications detected. RESULTS: All chest ports were placed via the internal jugular vein using both fluoroscopic and ultrasound guidance. The technical success rate was 99.3% (137/138). All catheter or port-related complications were retrospectively assessed. Sixteen complications were detected during the follow-up period, and catheter removal was required in 10 patients. CONCLUSIONS: Image-guided central venous port catheter implantation is a very safe procedure with a low rate of complications. The typical imaging features of common and uncommon complications are very helpful in establishing the correct diagnosis and thus tailoring the appropriate therapy. PMID- 22307470 TI - Spontaneous fracture and migration of distal segment of a peripherally inserted central venous catheter to heart in a neonate. PMID- 22307471 TI - Vessel health and preservation (Part 1): a new evidence-based approach to vascular access selection and management. AB - Vascular access for the infusion of medications and solutions requires timely assessment, planning, insertion, and assessment. Traditional vascular access is reactive, painful, and ineffective, often resulting in the exhaustion of peripheral veins prior to consideration of other access options. Evidence suggests clinical pathways improve outcomes by reducing variations and establishing processes to assess and coordinate care, minimizing fragmentation and cost. Implementation of a vascular access clinical pathway leads to the intentional selection of the best vascular access device for the patient specific to the individual diagnosis, treatment plan, current medical condition, and the patient's vessel health (1). The Vessel Health and Preservation (VHP) programme incorporates evidence-based practices focused on timely, intentional proactive device selection implemented within 24 hours of admission into any acute facility. VHP is an all-inclusive clinical pathway, guiding clinicians from device selection through patient discharge, including daily assessment. Initiation of the VHP programme within a facility provides a systematic pathway to improve vascular access selection and patient care, allowing for the reduction of variations and roadblocks in care while increasing positive patient outcomes and satisfaction. Patient safety and preservation of vessel health is the ultimate goal. PMID- 22307472 TI - Management of treatment-associated toxicites of anti-angiogenic therapy in patients with brain tumors. AB - Anti-angiogenic therapies, including bevacizumab, are being used with increasing frequency in the management of malignant glioma. Common clinically significant toxicities include hypertension and proteinuria, poor wound healing, and the potential for thromboembolic events. Literature related to the use of bevacizumab in malignant glioma, reported toxicities in this patient population, and management of these toxicities was reviewed. Recommendations for assessment and management are provided. Anti-angiogenic therapies will continue to have a role in the treatment of malignant glioma. Further studies of the prevention, assessment, and management of these toxicities are warranted. PMID- 22307473 TI - Cognitive functioning in newly presenting patients with supratentorial intracranial tumors: is there a role for inspection time? AB - Quantifying the extent of cognitive dysfunction in patients with intracranial tumors is important to monitor treatment effects and assess patients' needs. Inspection time, a measure of the efficiency of visual information processing, was evaluated, and its usefulness in patients with intracranial tumors was compared with that of other widely used cognitive tests. Newly presenting inpatients with supratentorial intracranial tumors (n = 118) underwent preoperative assessment using inspection time and a number of other measures of cognitive function, mood, and functional status. The brain tumor cohort was compared with patients admitted for elective spinal surgery (n = 85) and a healthy control group (n = 80). Analysis of covariance was used to compare the performance of the 3 groups. The brain tumor cohort had significantly lower inspection time scores than the spinal surgery group (P = .005) and the healthy volunteer control group (P < .001). The effect size was moderate. There was a large effect size of participant group for the Rey Auditory Verbal Learning Test, Digit Symbol-Coding, and Verbal Fluency (P = .002). The performance of patients with brain tumors was significantly worse than that of both of the control groups. Inspection time was well-tolerated by patients with intracranial tumors. However, inspection time is neither as easy to perform nor as sensitive as some other measures of cognitive function. Although its lack of any motor speed or coordination requirements, conceptual simplicity, repeatability, and relative lack of learning effect make inspection time a potentially useful tool in clinical neuro-oncology, practical considerations will limit its use. PMID- 22307474 TI - Oncolytic measles virus prolongs survival in a murine model of cerebral spinal fluid-disseminated medulloblastoma. AB - Medulloblastoma is the most common malignant brain tumor of childhood. Although the survival rate of afflicted children has improved considerably over the past several years, a subset of these patients will present with disseminated disease and face a much bleaker prognosis. In addition, patients may present with disseminated disease at recurrence. We previously demonstrated the efficacy of a recombinant oncolytic measles virus (MV) to treat localized medulloblastoma in a mouse xenograft model. In the present study, we sought to extend our findings to the treatment of disseminated disease. To this end, we developed and characterized a mouse xenograft model of disseminated medulloblastoma using serial bioluminescent imaging techniques in combination with histopathological examination. Mice injected with medulloblastoma cells into their right lateral ventricle showed tumor growth in their ventricles and in both intracranial and spinal subarachnoid spaces, closely recapitulating the human disease. Subsequent intraventricular administration of MV resulted in stabilization and shrinkage of the tumor, significantly prolonging the survival of the treated animals, compared with those treated with an inactivated virus. These data demonstrate that oncolytic MV may be of use in treating disseminated medulloblastoma. In addition, our protocol of intraventricular tumor cell injection, followed by bioluminescent imaging coupled with histopathological examination, provides a model for use in evaluating future recombinant oncolytic viruses and other preclinical therapeutic approaches for disseminated medulloblastoma. PMID- 22307475 TI - Systematic review of supportive care needs in patients with primary malignant brain tumors. AB - In adults, primary malignant brain tumors (PMBT) are rare, but they have a devastating impact and the chances for survival are limited. UK clinical guidance on supportive care for patients with brain and central nervous system tumors was published in 2006 and relied on very limited evidence. The current article reviews literature from 2005 through 2011 on the psychosocial and supportive needs of patients with PMBT and their families or caregivers. Searches were conducted in PubMed, Web of Science, Psychinfo, Cochrane, Scopus, ASSIA, and Sciencedirect. The search initially yielded 6220 articles, of which 60 were found to be eligible (1%). Eleven qualitative and 49 quantitative studies are reviewed here and mapped onto the structure of the existing UK clinical guidance. Studies suggest rates of depression and anxiety up to 48% in patients and up to 40% in caregivers, with many unmet needs and dissatisfaction with health care provider communication and information. Cognitive deficits increase as the disease progresses, hampering communication and decision-making. A range of neurological and physical symptoms at the end of life need recognition. Some successful supportive and neuropsychological interventions are reported. Although the volume of available studies has increased since UK guidance, many remain observational in nature, with few trials of interventions. However, this review provides an up to date resource for clinicians involved with patients with PMBT, describing current knowledge on patients' psychosocial needs, the type of care which has been found to be beneficial, and highlighting areas where more research needs to be done. PMID- 22307477 TI - The impact of vitamin A restriction and ADH1C genotype on marbling in feedlot steers. AB - A novel SNP was discovered within the promoter region of alcohol dehydrogenase 1C (ADH1C c.-64T>C), the C allele eliminating a potential binding site for the transcription factor C/EPBalpha. The purpose of this study was to examine if an interaction between this SNP and vitamin A restriction had an effect on carcass characteristics in beef cattle. Following backgrounding on a beta-carotene deficient diet, 130 steers (50 TT, 50 CT, and 30 CC) were finished for 5 mo and received either no supplemental vitamin A (unsupplemented) or 750,000 IU/mo (supplemented). A subgroup of 5 steers * genotype(-1) * treatment(-1) was randomly selected for pre- and postfinishing liver biopsies to assess vitamin A status and measure gene expression. Unsupplemented steers (Bos taurus) had significantly greater (P < 0.05) marbling scores than supplemented steers. There was a significant interaction between genotype and vitamin A supplementation on ether-extractable intramuscular fat (IMF). Within the unsupplemented treatment, TT steers had nearly 23% greater IMF than CC steers. Additionally, unsupplemented TT steers had over 24% greater IMF than supplemented TT steers. Expression of ADH1C in the liver was additive with each additional T allele, potentially due to the elimination of a possible binding site for C/EBPalpha. It is plausible that CC cattle have reduced ability to metabolize retinol to retinaldehyde (and subsequently retinoic acid) and that a phenotypic effect is only observed when vitamin A is limiting. Therefore, ADH1C c.-64T>C genotype, in combination with reduced vitamin A supplementation, could potentially be implemented in marker assisted management to maximize marbling in finishing cattle. PMID- 22307478 TI - Predicting milk yield and composition in lactating sows: a Bayesian approach. AB - The objective of this study was to develop a framework describing the milk production curve in sows as affected by parity, method of milk yield (MY) determination, litter size (LS), and litter gain (LG). A database containing data on LS, LG, dietary protein and fat content, MY, and composition measured on more than 1 d during lactation and method for determining MY from peer reviewed publications and individual sow data from 3 studies was constructed. A Bayesian hierarchical model was developed to analyze milk production data. The classical Wood curve was used to model time trends in MY during lactation, and it was re parameterized expressing the natural logarithm of MY values at d 5, 20, and 30 as functional parameters. The model incorporated random effects of experiment, sow nested within experiment, and fixed effects of LS, LG, parity, and method through the functional parameters of the Wood curve. A second set of models were constructed to analyze milk composition data, including day in milk, LS, dietary protein, and fat contents. Four scenarios with different LG and LS were constructed using the framework to estimate the energy output in milk at different days during lactation. The estimated energy output was compared with energy output values calculated using the 1998 NRC method. Milk yield was underestimated by approximately 20% with the weigh-suckle-weigh technique compared with the deuterium oxide dilution technique (P < 0.001). The mean LG and LS for the dataset were 2.05 kg/d (1.0; 3.3) and 9.5 piglets (5; 14), respectively. The MY was affected by LS on d 5 and 20 (P < 0.001) and by LG on d 20 (P < 0.001) and d 30 (P = 0.004). The mean time to peak lactation was 18.7 d (SD = 1.06) postpartum and mean MY at peak lactation was 9.23 kg (SD = 0.14). The average protein, lactose, and fat content of milk was 5.22 (SD = 0.06), 5.41 (SD = 0.08), and 7.32% (SD = 0.17%), respectively. The NE requirement for lactation increased from d 5 to 20 because of increased MY. Requirements also increased with increasing LG and LS. The framework could be used to predict energy and protein requirements for lactation under different production expectations and can be incorporated into a whole animal model for determination of energy and nutrient requirements for lactating sows, which can optimize sow performance and longevity. PMID- 22307479 TI - Selenium status in adult cats and dogs fed high levels of dietary inorganic and organic selenium. AB - Cats (Felis catus) maintain greater blood Se concentrations compared with dogs (Canis familiaris) and, unlike dogs, show no signs of chronic Se toxicity (selenosis) when fed dietary organic Se (selenomethionine) concentrations of 10 MUg/g DM. This study investigated the response of cats and dogs to high dietary concentrations of sodium selenite and organic Se to determine differences in metabolism between both species. In 2 consecutive studies, 18 adult cats and 18 adult dogs of with equal numbers of each sex were fed a control diet (0.6 MUg Se/g DM) or the control diet supplemented to 8 to 10 MUg Se/g DM from Na(2)SeO(3) or organic Se for 3 wk. All animals were fed the control diet 1 mo before the start of the study and blood samples were taken on d 0 and 21. The Se balance was assessed during the final week and a liver biopsy was obtained on the final day of the study. Measurements included plasma Se concentrations, plasma glutathione peroxidise (GPx) activities, plasma Se clearance, Se intake, and urinary Se excretion. No clinical signs of selenosis were observed in the cats or dogs, and apart from Se clearance, form of Se had no effect on any of the measurements. Apparent fecal Se absorption was greater in the dogs fed both forms of Se, while greater plasma Se concentrations were observed in the cats on both the control and supplemented diet (P = 0.034). Cats fed the supplemented diets had lower hepatic Se concentrations (P < 0.001) and excreted more Se in urine (P < 0.001) compared with dogs. Furthermore, cats fed the Na(2)SeO(3) supplement had greater Se clearance rates than dogs (P < 0.001). There was no effect of species on plasma GPx activity. We conclude that cats can tolerate greater dietary Se concentrations as they are more efficient at excreting excess Se in the urine and storing less Se in the liver. PMID- 22307481 TI - Chilling rate effects on pork loin tenderness in commercial processing plants. AB - The present experiment was conducted to provide a large-scale objective comparison of pork LM tenderness and other meat quality traits among packing plants that differ in stunning method and carcass chilling rate. For each of 2 replicates, pigs were sourced from a single barn of a commercial finishing operation that fed pigs from a single terminal crossbred line. On each day, 3 trucks were loaded, with each of those trucks delivering the pigs to a different plant. Plant A used CO(2) stunning and conventional spray chilling; Plant B used CO(2) stunning and blast chilling; and Plant C used electrical stunning and blast chilling. The boneless, vacuum-packaged loin was obtained from the left side of each carcass (n = 597; 100 . plant(-1) . replicate(-1)). As designed, HCW, LM depth, and LM intramuscular fat percentage did not differ among plants (P > 0.05). By 1.67 h postmortem (1 h after the carcasses exited the harvest floor), the average deep LM temperature was >10 degrees C warmer for Plant A than Plants B and C (32.1 degrees C, 21.6 degrees C, and 19.3 degrees C, for Plants A, B, and C, respectively) and deep LM temperature continued to be >10 degrees C warmer for Plant A until 4.17 h or 6.33 h postmortem than for Plants C and B, respectively. Both plants that used blast chilling produced loins with greater LM slice shear force at 15 d postmortem than did the plant that used conventional spray chilling (P < 0.0001). The frequency of loins with excessively high (>25 kg) LM slice shear force values was greater for Plant B than Plant A (14.7% vs. 1%; P < 0.01). Among all the traits studied, including visual and instrumental evaluations of LM color, ultimate pH, marbling score, and lean color stability, the only other difference between Plants A and B was that purge loss during 13 d (from d 1 to 14) of vacuum-packaged storage was greater for Plant B (P < 0.05). That is, with this sample of pigs and CO(2) stunning, no loin quality advantages were detected for blast chilling. Regardless of chilling method, CO(2) stunning resulted in darker LM lean color and greater LM water-holding capacity than did electrical stunning (P < 0.05). This research shows that differences in chilling systems among pork packing plants can have a strong influence on loin chop tenderness. PMID- 22307482 TI - Comparative effects of level of dietary fiber and sanitary conditions on the growth and health of weanling pigs. AB - There are conflicting results on the growth and health of weanling pigs (Sus scrofa) fed high-fiber diets, and responses may differ according to sanitary conditions. This study was conducted to explore the growth, health, and fecal microbiota of weanling pigs fed either low- or high-fiber diets in 2 different sanitary conditions. Forty-eight pigs weaned at 28 d of age were individually housed in "good" (clean) or "poor" (unclean) sanitary conditions. During 2 consecutive phases, pigs were fed 2 diets containing a low (control) or high level of fiber: 121 or 169 g/kg total dietary fiber (TDF) for Phase I and 146 or 217 g/kg for Phase II, which lasted 15 and 20 d, respectively. This led to 4 experimental treatments in Phase I in a 2 * 2 factorial arrangement (2 sanitary conditions * 2 diets) and 8 experimental treatments in Phase II in a 2 * 2 * 2 factorial arrangement (2 sanitary conditions * 2 diets in Phase I * 2 diets in Phase II). The poor sanitary conditions led to a reduced G:F (0.617 vs. 0.680 for poor and good sanitary conditions, respectively; P = 0.01) over the entire experimental period. The number of pigs with diarrhea in Phase I tended to be greater in the poor sanitary conditions with the high-fiber diet than the control diet (7 vs. 3 pigs, P = 0.07). Enterococcus was prominent in feces of these diarrheic pigs. At 5 wk after weaning, compared with good sanitary conditions, the fecal microbiota of pigs housed in poor sanitary conditions was characterized by more Lactobacillus (9.24 vs. 8.34 log cfu/g, P < 0.001), more Enterobacteria (6.69 vs. 5.58 log cfu/g, P < 0.001), and less anaerobic sulfite bacteria (3.72 vs. 5.87 log cfu/g; P < 0.001). The feces of pigs in poor sanitary conditions contained more total VFA and proportionally more butyrate (9.7 vs. 5.7% for poor and good conditions, respectively, independently of dietary treatment, P < 0.001). At 5 wk after weaning, feces of pigs fed the high-fiber diet during Phase II contained less Enterococcus bacteria than pigs fed the control diet (4.06 vs. 4.56 log cfu/g; P = 0.05), and more total VFA with a decreased proportion of branched-chain fatty acids (5.0 vs. 6.1%; P = 0.006). To conclude, feeding pigs a high-fiber diet in the immediate period after weaning is probably an additional risk factor for slower BW gain, especially in poor sanitary conditions. PMID- 22307483 TI - Ruminant Nutrition Symposium: modulation of metabolism through nutrition and management. PMID- 22307484 TI - Adipogenic gene expression and fatty acid composition in subcutaneous adipose tissue depots of Angus steers between 9 and 16 months of age. AB - We have demonstrated that among carcass adipose tissue depots, brisket subcutaneous adipose tissue contains the greatest concentration of MUFA and lowest concentration of SFA. Therefore, we hypothesized that brisket subcutaneous adipose tissue depots would exhibit greater adipogenic gene expression over time than other major subcutaneous adipose tissue depots. Four Angus steers, each at 9, 12, 14, and 16 mo of age, were harvested and fresh subcutaneous adipose tissue samples were collected from over the brisket, chuck, rib, loin, sirloin, round, flank, and plate. Relative gene expression for C/EBPbeta, PPARgamma, carnitine palmitoyltransferase-1 beta (CPT-1beta), stearoyl-coenzyme A desaturase (SCD), AMP-activated protein kinase alpha (AMPKalpha), and G-coupled protein receptor 43 (GPR43) was analyzed by quantitative real-time PCR. Expression of C/EBPbeta, PPARgamma, and CPT-1beta was greatest at 12 to 14 mo of age (all P < 0.0001) and declined to very low abundance by 16 mo of age in all depots. Expression of PPARgamma and CPT-1beta was greater (P < 0.03) in flank, rib, and sirloin subcutaneous adipose tissues than in brisket and round adipose tissues. The expression of the SCD gene did not differ among the 4 age groups (P = 0.95). The palmitoleic:stearic acid ratio (an estimate of SCD activity) was greater (P < 0.001) in the subcutaneous adipose tissues from brisket, plate, and round than in the loin, rib, and sirloin. Conversely, subcutaneous adipose tissue from the loin, rib, and sirloin had greater (P < 0.001) SCD gene expression than the brisket, plate, and round. In general, subcutaneous adipose tissues with the highest concentration of MUFA and least SFA consistently exhibited the least SCD gene expression and adipogenic gene expression. We conclude that MUFA in the brisket and other depots with large SCD indices were deposited before 9 mo of age, during a time when the subcutaneous adipocytes were highly differentiated. PMID- 22307485 TI - Antioxidant supplements in exercise: worse than useless? PMID- 22307488 TI - Zinc and liver disease. AB - Zinc is an essential trace element required for normal cell growth, development, and differentiation. It is involved in DNA synthesis, RNA transcription, and cell division and activation. It is a critical component in many zinc protein/enzymes, including critical zinc transcription factors. Zinc deficiency/altered metabolism is observed in many types of liver disease, including alcoholic liver disease (ALD) and viral liver disease. Some of the mechanisms for zinc deficiency/altered metabolism include decreased dietary intake, increased urinary excretion, activation of certain zinc transporters, and induction of hepatic metallothionein. Zinc deficiency may manifest itself in many ways in liver disease, including skin lesions, poor wound healing/liver regeneration, altered mental status, or altered immune function. Zinc supplementation has been documented to block/attenuate experimental ALD through multiple processes, including stabilization of gut-barrier function, decreasing endotoxemia, decreasing proinflammatory cytokine production, decreasing oxidative stress, and attenuating apoptotic hepatocyte death. Clinical trials in human liver disease are limited in size and quality, but it is clear that zinc supplementation reverses clinical signs of zinc deficiency in patients with liver disease. Some studies suggest improvement in liver function in both ALD and hepatitis C following zinc supplementation, and 1 study suggested improved fibrosis markers in hepatitis C patients. The dose of zinc used for treatment of liver disease is usually 50 mg of elemental zinc taken with a meal to decrease the potential side effect of nausea. PMID- 22307489 TI - Selenium supplementation in the critically ill. AB - Selenium (Se) is an essential trace element with antioxidant, immunological, and anti-inflammatory properties, which are attributed to its presence in selenoproteins, as the 21st amino acid selenocysteine. These selenoenzymes are involved in redox signaling, antioxidant defense, thyroid hormone metabolism, and immune responses. Dietary intakes differ considerably between geographical regions, due to variability of the Se food content, leading to differences in dietary reference intakes and toxicity cautions. Critical illness with systemic inflammatory response syndrome (SIRS) is characterized by Se depletion with high morbidity and mortality. Se status correlates well with clinical outcome in SIRS and may be useful as an early predictor of survival. Several investigators have evaluated the benefits of Se supplementation for the critically ill, either as monotherapy or in an antioxidant micronutrient combination. Pharmaconutrition, with high-dose Se (from 500-1600 ug/d) involving an initial loading bolus, followed by continuous infusion, appears to be safe and efficacious, with evidence that it can improve clinical outcome by reducing illness severity, infectious complications, and decreasing mortality in the intensive care unit (ICU). We now have a clearer understanding of the pharmacokinetics of the initial and transient pro-oxidant effect of an intravenous bolus of selenite and the antioxidant effect of continuous infusion. Better biomarkers to ascertain optimum Se requirements for individual patients are now needed, and clinical practice guidelines need improvement. Nevertheless, sufficient evidence is available to consider initiating high-dose intravenous Se therapy routinely in critically ill SIRS patients, immediately on admission to the ICU. PMID- 22307490 TI - Refeeding syndrome or refeeding hypophosphatemia: a systematic review of cases. AB - Nutrition support clinicians refer to the abnormalities in laboratory data and changes in clinical signs and symptoms that follow refeeding of starved or malnourished patients as refeeding syndrome. Theoretical descriptions of refeeding syndrome include a complex and extensive list of changes, such as hypophosphatemia, hypomagnesemia, hypokalemia, hyponatremia, hypocalcemia, hyperglycemia, and vitamin deficiency--all of which are accompanied by clinical signs and symptoms. In practice, clinicians see asymptomatic refeeding hypophosphatemia more often than a full-blown syndrome with multiple laboratory and clinical abnormalities. Confusion results because there is no widely accepted or uniformly applied set of defining characteristics for diagnosing refeeding syndrome. To gain insight into the clinical characteristics of refeeding syndrome described in the literature, a systematic review of reported cases and case series was conducted. Since 2000, 20 authors described 27 cases that contained sufficient data for review. Hypophosphatemia occurred in 26 patients (96%). While 19 patients (71%) experienced at least 1 other laboratory abnormality, only 14 (51%) exhibited a consistent pattern of abnormally low phosphorus and magnesium levels. Seven patients had hypocalcemia (26%), and hyponatremia was reported in 3 patients (11%). There were no reports of hyperglycemia. Mean data reported in case series containing data from 63 patients showed that hypophosphatemia was a consistent finding but that other abnormalities were not consistently identified. Findings suggest that refeeding hypophosphatemia is not accompanied by a consistent pattern of biochemical or clinical abnormalities among case reports or case series of patients reported to have refeeding syndrome. PMID- 22307491 TI - HIV medications: an update and review of metabolic complications. AB - In the past 30 years, medical advances for those with human immunodeficiency virus (HIV) have reduced morbidity and mortality to extend life with highly active antiretroviral therapy (HAART) and with the continued development of new therapies. With this success, HIV is being managed chronically, but other health issues of an aging HIV-infected population have emerged. The challenges of treating HIV infection have shifted from AIDS-related mortality improvements to drug-induced disease from HAART, including cardiovascular disease, metabolic disorders, and bone health. Prolonged use of antiretroviral therapy maintaining immune restoration appears to represent additional, ongoing risk factors for the development of these metabolic complications. These drug-related problems continue to challenge patients and clinicians in the management of HIV disease, as well as ongoing research for drug development improvements to minimize these risks. These health risks imposed by HAART must be vigilantly monitored and aggressively addressed to improve the overall health of those treated for HIV infection. PMID- 22307492 TI - Enteral feeding patients with gastric outlet obstruction. AB - Patients with upper gastrointestinal obstructions were previously managed with gastric decompression and parenteral feeding. The authors present their experience in 50 patients with obstructions chiefly due to complicated severe acute (n = 31) or chronic cystic pancreatitis (n = 11) using a double-lumen nasogastric decompression and jejunal feeding tube system (NGJ) held in place with a nasal bridle that passes through the obstructed gastroduodenal segments, allowing distal jejunal feeding, and at the same time decompresses the stomach to prevent vomiting and aspiration. The tip of the jejunal tube was placed approximately 40 cm down the jejunum to maintain pancreatic rest. Duration of feeding ranged from 1-145 days (median 25 days); 19 patients were discharged home with tube feeds. Only 1 patient could not tolerate feeding and needed to be converted to parenteral feeding. Average tube life was 14 days, with replacement being needed most commonly for kinking or clogging of the jejunal tube (56%) or accidental dislodgement (24%). The obstruction resolved spontaneously in 60%, allowing resumption of normal eating. Of the patients with severe acute pancreatitis or pancreatic pseudocysts, pancreatic rest resulted in resolution of the disease without surgery in 87%, and need for surgery in the remainder was put off for 31-76 days. Seven patients died predominantly of complications of acute pancreatitis between 1 and 31 days. In conclusion, NGJ feeding provides a relatively safe conservative management for critically ill patients with upper gastrointestinal obstructions, reducing the need for surgery and parenteral feeding. PMID- 22307493 TI - Determinant factors of the viscosity of enteral formulas: basic analysis of thickened enteral formulas. AB - BACKGROUND: Thickened enteral formula (TEF), which is made by adding thickener to enteral formula, has been used mainly in Japan to reduce the incidence of clinical complications associated with enteral nutrition. However, the optimal viscosity of TEF needed to achieve a high efficiency is different for each medical complication and for individual patients. METHODS: The viscosity of TEF, which consists of enteral formula and thickener, was determined by 5 factors: (1) formula energy density, (2) formula temperature, (3) stirring speed, (4) stirring time, and (5) time elapsed since preparation. Then, the changing index (CI) was calculated for each of the 5 factors to determine which exerts the most influence on TEF viscosities. RESULTS: The most influential factor (CI >=-50%) for the decrease in TEF viscosity was formula energy density. In contrast, the most influential factors (CI >=50%) for the increase in TEF viscosity were stirring time and time elapsed since preparation. CONCLUSION: The results of this study indicate that formula energy density, stirring time, and time elapsed since preparation are the most influential factors to consider during manipulation of TEF viscosity. PMID- 22307494 TI - Supplementation of essential amino acids may reduce the occurrence of infections in rehabilitation patients with brain injury. AB - BACKGROUND: To investigate whether supplementation with oral essential amino acids (EAAs) may reduce the occurrence of nosocomial infection among patients with brain injury (BI: stroke, trauma, anoxic coma). METHODS: Patients (n = 125; 77 men, 48 women; mean age 63 +/- 15 years) with stroke (68.8%), subarachnoid hemorrhage (17.6%), traumatic BI (7.2%), and anoxic BI (6.4%) 88 +/- 15 days after the index event. Patients were randomly assigned to 2 months of oral EAAs (n = 63; 8 g/d) or placebo (n = 62). RESULTS: Over the first month of rehabilitation, there were 60 infections in the whole population of 125 patients (48%); however, the rate was 23.2% lower in the EAA group (23 episodes/63 patients; 36.5%) than in the placebo group (37 episodes/62 patients; 59.7%) (P < .01). The types of infection were similarly distributed between the 2 groups. Serum levels of prealbumin <20 mg/dL and C-reactive protein (CRP) >0.3 mg/dL were the best predictors of future infection (prealbumin: odds ratio [OR] = 4.17, confidence interval [CI] 1.84-9.45, P < .001; CRP: OR = 3.8, CI 1.71-8.44, P < .001). CONCLUSION: Supplementary EAAs may reduce the occurrence of nosocomial infections in rehabilitation patients with BI. Prealbumin and CRP are the best predictors of future infections. PMID- 22307495 TI - Influence of Roux-en-Y gastric bypass surgery on vitamin C, myeloperoxidase, and oral clinical manifestations: a 2-year follow-up study. AB - BACKGROUND: Bariatric surgery influences the intake and absorption of nutrients, which, when associated with vomiting, can damage the oral cavity. The serum concentrations of vitamin C and myeloperoxidase (MPO) and oral clinical manifestations were examined in patients 2 years after Roux-en-Y gastric bypass (RYGB). METHODS: Clinical prospective study with control group (CG; n = 26), assessed only once, and the bariatric group (BG; n = 26), assessed in the basal period and at 12 and 24 months after surgery. The mean ages in the CG and BG were 37.8 +/- 1.51 and 39.6 +/- 1.93 years, respectively, and their body mass indices were 22.07 +/- 0.29 and 45.62 +/- 1.46 kg/m(2), respectively. RESULTS: At 12 months after surgery, increased episodes of vomiting (P < .001) and dental hypersensitivity (P = .012) were observed, with a reduction in the saliva buffering capacity of 21.3% +/- 2.9% (P = .004). At 24 months after RYGB, a significant reduction in serum vitamin C was detected (32.9% +/- 5.3%, P < .001), and MPO values were higher than in the basal period (P = .032). With regard to oral hygiene habits, 92.3% of patients reported frequent tooth brushing and 96.1% used fluoride, which were similar across the 2 years. However, dental hypersensitivity (P = .048) was significantly increased than baseline. CONCLUSIONS: The results demonstrated that vitamin C deficiency and increased vomiting after gastric bypass for morbid obesity may contribute to increased periodontal disease. The fact that it is impossible to determine which factor or factors (diet, poor compliance with supplementation, vomiting, poor oral hygiene) contributed to the dental problems in these patients is a shortcoming of the report. PMID- 22307496 TI - Interprofessional group intervention for parents of children age 3 and younger with feeding difficulties: pilot program evaluation. AB - BACKGROUND: Feeding difficulties are common with an estimated prevalence of 25% 45% in normally developing children. Clinicians and researchers emphasize the need for timely and effective treatment because a proportion of children develop failure to thrive with possible long-term impairments. Interprofessional assessment and treatment has emerged as an optimal approach to reduce parental anxiety and increase children's acceptance of a wider variety of foods. METHODS: Participants, including 30 children (mean age of 26 +/- 8.2 months) meeting inclusion/exclusion criteria and their families, attended a program consisting of 4 sessions, and a 1-month follow-up. Parents completed the Behavioral Pediatrics Feeding Assessment Scale pre- and posttreatment and Goal Attainment Scaling (GAS). RESULTS: Paired t tests indicate that the composite scores for frequency of feeding difficulties were on average significantly less posttreatment compared with pretreatment, and composite scores for frequency of parental problems with feeding were also significantly less posttreatment. These results were reflected in the composite scores for both feeding difficulties and parental problems with feeding on child- and parent-related items. The median for the GAS was +2 (range, -2 to +2). Written parental responses in the GAS reflected 2 major themes: satisfaction with the program and a desire for more individualized attention. CONCLUSIONS: These results offer preliminary evidence suggesting that an interprofessionally led parent group, with contributions from clinical nutrition, occupational therapy, psychology, and speech-language pathology professionals, is effective in treating young children with feeding difficulties. PMID- 22307497 TI - GDx VCC measurements and blue-on-yellow perimetry in ocular hypertension. AB - The aim of this work was to investigate the correlation between scanning laser polarimetry with variable corneal compensation (GDx VCC) parameters and blue-on yellow perimetry (B/YP) indices in ocular hypertension (OHT). One eye each of 52 patients with OHT (with a normal visual field, a normal optic nerve, and an untreated IOP > 21 mmHg) was chosen. All patients were examined with the Octopus 101 automated perimetry dG2 program using the dynamic/normal strategy (white-on white perimetry, W/WP), with the dG2 program using the dynamic strategy/BY method (blue-on-yellow perimetry, B/YP), and with GDx VCC. Seven of the 52 OHT patients had both B/YP visual field loss and retinal nerve fiber layer (RNFL) defects with the GDx VCC measurements, and four patients demonstrated regions of B/YP visual field defects with corresponding RNFL defects on GDx VCC examination. A mild significant correlation was found between B/YP mean sensitivity (MS) and the superior average (R (2) =0.138, p = 0.049). No significant correlation was found between the W/WP indices and GDx VCC parameters. B/YP MS correlated with the superior average of GDx VCC in OHT patients. The findings brought up the possibility of using both techniques for clinical examination to yield converging data. PMID- 22307498 TI - The two-step biotransformation of monosodium glutamate to GABA by Lactobacillus brevis growing and resting cells. AB - Gama-aminobutyric acid (GABA) is a natural functional amino acid. In the current study, Lactobacillus brevis TCCC13007, a high GABA-producing strain, was isolated from naturally pickled Chinese vegetables. A two-step cellular bioconversion process was established using L. brevis TCCC13007 for the production of GABA. First, L. brevis cells were grown anaerobically in 7% monosodium glutamate (MSG) containing medium at an initial pH of 6.0 and a controlled pH of 4.6 for 16 to 66 h; approximately 38 g L(-1) of GABA was obtained after 66 h of fermentation at a conversion rate of 98.6%. In the second stage of the process, about 7.6 g L(-1) of GABA was produced three more times at a conversion rate of 92.2% using the same batch of resting cells in the substrate-containing buffer under optimized conditions. Thus, the total GABA yield reached 61 g L(-1). A model system for the biotransformation of MSG to GABA was established using L. brevis TCCC13007 resting cells. The reaction rates were found to follow the classic Michaelis Menten equation at low substrate concentrations (<80 mM). Kinetic analysis of the biotransformation revealed that L. brevis TCCC13007 resting cells produced GABA similar to that produced by purified glutamate decarboxylase from L. brevis. PMID- 22307499 TI - Optimization of the production of gurmarin, a sweet-taste-suppressing protein, secreted by the methylotrophic yeast Pichia pastoris. AB - Gurmarin, a 35-residue polypeptide, is known to selectively inhibit responses to sweet substances in rodents without affecting responses to other basic taste stimuli, such as NaCl, HCl, and quinine. Here, we report the heterologous expression of gurmarin using the methylotrophic yeast Pichia pastoris. Gurmarin was secreted into the buffered minimal medium using the alpha-factor preprosequence without the EAEA spacer peptide of Saccharomyces cerevisiae and was under the control of the methanol-inducible alcohol oxidase promoter. We found that gurmarin accumulated in the yeast culture medium reaching 5 mg per liter of culture over an expression period of 4 days. To compare the production level and the signal peptide processing, the N-terminal amino acid of gurmarin was substituted by a glutamic acid residue. This construct resulted in a 6-fold increase in the level of gurmarin secretion leading to 30 mg of purified protein per liter of culture. Purified recombinant gurmarin resulting from both constructs was characterized using mass spectrometry. Circular dichroism and NMR spectroscopy revealed that recombinant gurmarin was properly folded and had secondary and tertiary structures. We also confirmed its capability to inhibit the rat heterodimeric sweet taste T1R2/T1R3 receptor by functional expression in human embryonic kidney HEK293T cells. The high level of fully active gurmarin obtained in P. pastoris makes this expression system attractive for fermentor growth and pharmacological investigations of taste receptor and gurmarin functions. PMID- 22307500 TI - Impact of each individual component of the mutated PTS(Nag) on glucose uptake and phosphorylation in Ralstonia eutropha G+1. AB - A recent study of the UV-generated glucose-utilizing mutant Ralstonia eutropha G+1 comprising transcriptomic and proteomic analyses revealed clear evidence that glucose is transported by the N-acetylglucosamine-specific phosphotransferase system (PTS(Nag)), which is overexpressed in this mutant due to a derepression of the encoding nag operon by an identified insertion mutation in nagR (Raberg et al., Appl Environ Microbiol 77:2058-2070, 2011). The inability of the defined deletion mutant R. eutropha G+1?nagFEC to utilize glucose confirms this finding. Furthermore, a missense mutation in nagE (membrane component comprising the cell membrane spanning EIIC(Nag) and the cytosolic domain EIIB(Nag)) was identified, which yields a substitution of an alanine by threonine at aa 153 of NagE and may affect glucose specificity of the mutated PTS(Nag) in R. eutropha G+1. The investigation of various generated deletion and substitution mutants of R. eutropha H16 and G+1 in this study was able to elucidate these phenomena. It could be shown that the porin NagC, encoded by nagC being part of the nag operon, is not necessary, while NagE is required and is probably responsible for glucose transport through the cell membrane. The intracellular phosphorylation of glucose is obviously mediated by the glucokinase GLK and not by NagF (cytosolic component comprising the three soluble domains EIIA(Nag), HPr(Nag), and EI(Nag)). Our data clearly indicate that the derepression of the nag operon is essential for glucose uptake. The point mutation in NagE is not an essential prerequisite for glucose transport although it increased glucose transport as observed in this study. PMID- 22307501 TI - Virulence factor prediction in Streptococcus pyogenes using classification and clustering based on microarray data. AB - Interesting biological information as, for example, gene expression data (microarrays), can be extracted from publicly available genomic data. As a starting point in order to narrow down the great possibilities of wet lab experiments, global high throughput data and available knowledge should be used to infer biological knowledge and emit biological hypothesis. Here, based on microarray data, we propose the use of cluster and classification methods that have become very popular and are implemented in freely available software in order to predict the participation in virulence mechanisms of different proteins coded by genes of the pathogen Streptococcus pyogenes. Confidence of predictions is based on classification errors of known genes and repetitive prediction by more than three methods. A special emphasis is done on the nonlinear kernel classification methods used. We propose a list of interesting candidates that could be virulence factors or that participate in the virulence process of S. pyogenes. Biological validations should start using this list of candidates as they show similar behavior to known virulence factors. PMID- 22307502 TI - Naumannella halotolerans gen. nov., sp. nov., a Gram-positive coccus of the family Propionibacteriaceae isolated from a pharmaceutical clean room and from food. AB - Four Gram-stain-positive, aerobic bacterial strains isolated from a pharmaceutical clean room (strain WS4616(T)), a dessert milk product (strain WS4617) and from raw milk (strains WS4623 and WS4624) were characterized using a polyphasic approach. Phylogenetic analyses based on 16S rRNA and recA gene sequences showed that they formed a distinct lineage within the family Propionibacteriaceae. Similarity values between 16S rRNA gene sequences of the four novel strains and the type species of all genera belonging to the family Propionibacteriaceae were 89.2-94.1%. The major cellular fatty acid was anteiso C(15:0) and the major polar lipids were diphosphatidylglycerol and phosphatidylglycerol. Respiratory quinones were MK-8(H(4)) and MK-9(H(4)). The cell-wall peptidoglycan of type A3gamma contained ll-diaminopimelic acid, alanine, glycine and glutamic acid. The G+C content of the genomic DNA of strain WS4616(T) was 67.7 mol%. The whole-cell sugar pattern contained ribose, mannose, arabinose, glucose and galactose. On the basis of phenotypic and genetic data, strains WS4616(T), WS4617, WS4623 and WS4624 are classified as members of a novel species in a new genus of the family Propionibacteriaceae, for which the name Naumannella halotolerans gen. nov., sp. nov. is proposed. The type strain is WS4616(T) ( = DSM 24323(T) = LMG 26184(T)) and three additional strains are WS4617, WS4623 and WS4624. PMID- 22307503 TI - Roseomonas riguiloci sp. nov., isolated from wetland freshwater. AB - A non-motile, coccobacillus-shaped and pink pigmented bacterium, designated strain 03SU10-P(T), was isolated from wetland freshwater (Woopo wetland, Republic of Korea). Cells were Gram reaction-negative and catalase- and oxidase-positive. The major fatty acids (>10% of total) were C(18:1)omega7c and summed feature 3 (iso-C(15:0) 2-OH and/or C(16:1)omega7c). The predominant respiratory lipoquinone was Q-10. The DNA G+C content was 68 mol%. The major polar lipids were phosphatidylethanolamine, phosphatidylcholine and an unknown aminolipid. Spermidine, putrescine and 1,3-diaminopropane were the major polyamines. A phylogenetic tree based on 16S rRNA gene sequence comparisons showed that strain 03SU10-P(T) formed an evolutionary lineage within the radiation enclosing the members of the genus Roseomonas. The nearest neighbour to the novel strain was Roseomonas stagni HS-69(T) (96.3% gene sequence similarity). The evidence provided by the polyphasic taxonomic approach used in this study indicated that strain 03SU10-P(T) could not be assigned to any recognized species; therefore a novel species is proposed, Roseomonas riguiloci sp. nov., with 03SU10-P(T) ( = KCTC 23339(T) = JCM 17520(T)) as the type strain. PMID- 22307504 TI - Brassicibacter mesophilus gen. nov., sp. nov., a strictly anaerobic bacterium isolated from food industry wastewater. AB - A novel mesophilic, strictly anaerobic bacterium, strain BM(T), was isolated from food industry wastewater. The cells were motile, non-spore-forming rods and stained Gram-negative. Growth of strain BM(T) was observed at 16-44 degrees C (optimum 37 degrees C) and pH 6.0-9.0 (optimum pH 7.5). The NaCl concentration range for growth was 0-8% (optimum 1.5%, w/v). Strain BM(T) was chemo organotrophic, using a few sugars and amino acids as sole carbon and energy sources. The fermentation products from peptone-yeast extract broth were propionate, formate, acetate, ethanol and isovalerate. Indole, NH(3) and H(2)S were produced from peptone. No respiratory quinones could be detected. The major fatty acids were iso-C(15:0) (39.3%), iso-C(15:0) dimethyl acetal (10.1%), anteiso-C(15:0) (7.6%), C(14:0) (6.1%) and C(16:0) (5.6%). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol and a number of unidentified aminoglycolipids, glycolipids and phospholipids. The DNA G+C content was 28.2 mol%. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that strain BM(T) was related to various genera of the family Clostridiaceae, and its closest relatives were Sporosalibacterium faouarense SOL3f37(T) (94.3% 16S rRNA gene sequence similarity), Proteiniborus ethanoligenes GW(T) (92.1%) and Clostridiisalibacter paucivorans 37HS60(T) (92.0%). In recognition of its distinct phenotypic and genotypic characteristics, isolate BM(T) is proposed to represent a novel species of a new genus, Brassicibacter mesophilus gen. nov., sp. nov. The type strain of Brassicibacter mesophilus is BM(T) ( = JCM 16868(T) = DSM 24659(T)). PMID- 22307505 TI - Dysgonomonas oryzarvi sp. nov., isolated from a microbial fuel cell. AB - A Gram-stain-negative, non-motile and coccoid- to short-rod-shaped bacterium, designated strain Dy73(T), was isolated from a microbial fuel cell that had been inoculated with rice paddy field soil and fed starch, peptone and fish extract as fuels. On the basis of 16S rRNA gene sequence phylogeny, strain Dy73(T) was affiliated with the genus Dysgonomonas in the phylum Bacteroidetes, and most closely related to Dysgonomonas mossii CCUG 43457(T) with a 16S rRNA gene sequence similarity value of 99.7 %. However, the DNA-DNA relatedness value between strain Dy73(T) and Dysgonomonas mossii CCUG 43457(T) was 34.8%. In addition, strain Dy73(T) was found to be different from other recognized species of the genus Dysgonomonas in taxonomically important traits, including habitat, DNA G+C content, bile resistance and fatty-acid composition. Based on these characteristics, strain Dy73(T) represents a novel species of the genus Dysgonomonas for which the name Dysgonomonas oryzarvi sp. nov. is proposed. The type strain is Dy73(T) ( = JCM 16859(T) = KCTC 5936(T)). PMID- 22307506 TI - Kordiimonas aestuarii sp. nov., a marine bacterium isolated from a tidal flat. AB - A Gram-staining negative, strictly aerobic bacterium, designated 101-1(T), was isolated from a sea tidal flat, Taean, Korea. The strain formed small light yellow, smooth, and circular colonies on marine agar. Cells were weakly halophilic, motile rods showing catalase- and oxidase-positive reactions. Growth of strain 101-1(T) was observed at 15-40 degrees C (optimum, 30 degrees C), pH 5.0-8.0 (optimum, pH 6.5-7.0) and 1.0-9.0% (w/v) NaCl (optimum, 2.0-3.5%). The G+C content of the genomic DNA was 53.3 mol%. Strain 101-1(T) contained ubiquinone-10 (Q-10) as the respiratory quinone and iso-C(17:1)omega9c, iso C(15:0) and iso-C(17:0) as major fatty acids. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain 101-1(T) formed a tight phylogenetic lineage with members of the genus Kordiimonas and was most closely related to Kordiimonas gwangyangensis GW14-5(T) and Kordiimonas lacus S3-22(T) with 97.3% and 96.3% 16S rRNA gene sequence similarities, respectively. The DNA-DNA relatedness values between strain 101-1(T) and K. gwangyangensis GW14-5(T) and K. lacus S3-22(T) were 24.8 +/- 4.4% and 32.2 +/- 3.6%, respectively. Based on the data from the phenotypic and genotypic studies, strain 101-1(T) represents a novel species of the genus Kordiimonas, for which the name Kordiimonas aestuarii sp. nov. is proposed. The type strain is 101-1(T) ( = KACC 16184(T) = JCM 17742(T)). PMID- 22307507 TI - Chitinophaga oryziterrae sp. nov., isolated from the rhizosphere soil of rice (Oryza sativa L.). AB - A novel bacterial strain, YC7001(T), was isolated from the rhizosphere soil of rice collected at Jinju, Korea, and was characterized using a polyphasic approach. Cells of strain YC7001(T) were Gram-negative-staining, yellow pigmented, rod-shaped, aerobic, heterotrophic and non-motile. Strain YC7001(T) grew optimally at 25-30 degrees C, pH 5.0-8.0 and degraded gelatin, cellulose and chitin. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain YC7001(T) belonged to the genus Chitinophaga in the family Chitinophagaceae. The most closely related species were Chitinophaga sancti NBRC 15057(T) (96.9%), Chitinophaga ginsengisoli Gsoil 052(T) (95.9%), Chitinophaga pinensis DSM 2588(T) (95.7%), Chitinophaga filiformis IFO 15056(T) (95.7%) and Chitinophaga niabensis JS13-10(T) (95.0%). The DNA-DNA relatedness value of strain YC7001(T) with C. sancti NBRC 15057(T) was 15.2 +/- 0.6%. Strain YC7001(T) contained MK-7 as the major menaquinone and homospermidine as the major polyamine. The major fatty acids of strain YC7001(T) were C(15:0) iso, C(16:1)omega5c and C(17:0) iso 3-OH. The polar lipids were phosphatidylethanolamine, unknown aminolipids and unknown lipids. The total genomic DNA G+C content was 41.3 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic analyses, strain YC7001(T) represents a novel species of the genus Chitinophaga, in the family Chitinophagaceae, for which the name Chitinophaga oryziterrae sp. nov. is proposed. The type strain is YC7001(T) ( = KACC 14533(T) = JCM 16595(T)). PMID- 22307508 TI - Sphingobacterium detergens sp. nov., a surfactant-producing bacterium isolated from soil. AB - A novel Gram-negative-staining strain, designated 6.2S(T), was isolated from a soil sample and identified as a biosurfactant producer. Its taxonomic position was investigated using a polyphasic approach. The cells were non-motile, non spore-forming rods. The organism grew optimally at 30-37 degrees C, with 0-3% (w/v) NaCl, and at pH 7.0. Based on 16S rRNA gene sequence analysis, strain 6.2S(T) was found to be a member of the genus Sphingobacterium and was most closely related to four type species of the genus, showing sequence similarities of 96.8-98.9%. Partial chaperonin 60 (cpn60) gene sequence analysis was useful in resolving the phylogenetic relationships between strain 6.2S(T) and closely related taxa, with similarities ranging from 85.5% (with Sphingobacterium thalpophilum DSM 11723(T)) to 90.3% (with Sphingobacterium canadense CR11(T) and Sphingobacterium multivorum JCM 21156(T)). The results of DNA-DNA hybridization experiments between the novel strain and its closest relatives gave a DNA-DNA relatedness value of less than 70%, and consequently confirmed that this new strain did not belong to a previously described species of the genus Sphingobacterium. The major fatty acids were summed feature 3 (iso-C(15:0) 2 OH and/or C(16:1)omega7c); iso-C(15:0); iso-C(17:0) 3-OH and C(16:0). The G+C content of the genomic DNA was 40.0 mol%. According to its phenotypic and genotypic characteristics and the phylogenetic data, strain 6.2S(T) represents a novel species of the genus Sphingobacterium, for which the name Sphingobacterium detergens sp. nov. is proposed. The type strain is 6.2S(T) ( = CECT 7938(T) = LMG 26465(T)). PMID- 22307509 TI - Galenea microaerophila gen. nov., sp. nov., a mesophilic, microaerophilic, chemosynthetic, thiosulfate-oxidizing bacterium isolated from a shallow-water hydrothermal vent. AB - A mesophilic, strictly microaerophilic, chemosynthetic bacterium, designated strain P2D(T), was isolated from the sediment of an active shallow-water hydrothermal vent in Paleochori Bay, on the Greek island of Milos. The cells were Gram-staining-negative rods that measured approximately 0.8-1.3 um in length and 0.4-0.5 um in width. Strain P2D(T) grew at 20-50 degrees C (optimum 35 degrees C), with 1.0-5.0% (w/v) NaCl (optimum 3.0%), and at pH 4.5-8.0 (optimum pH 5.5). The generation time under optimal conditions was 1.1 h. Growth occurred under chemolithoautotrophic conditions with S2O32- and CO(2) as the energy and carbon sources, respectively. Oxygen (5%) was used as sole terminal electron acceptor. No growth was observed in the presence of acetate, formate, lactate, tryptone or peptone. Chemolithoheterotrophic growth occurred when d-glucose or sucrose were present as carbon sources. None of the organic compounds tested was used as an electron donor. The genomic DNA G+C content of the novel strain was 44.9 mol%. In a phylogenetic analysis based on 16S rRNA gene sequences, strain P2D(T) was found to be most closely related to Thiomicrospira psychrophila DSM 13453(T) (92.8% sequence similarity). Based on the phylogenetic, physiological and chemotaxonomic evidence, strain P2D(T) represents a novel species of a new genus within the class Gammaproteobacteria of the family Piscirickettsiaceae, for which the name Galenea microaerophila gen. nov., sp. nov. is proposed. The type strain of the type species is P2D(T) ( = DSM 24963(T) = JCM 17795(T)). PMID- 22307510 TI - Haloferula chungangensis sp. nov., isolated from marine sediment. AB - A Gram-stain-negative, non-spore-forming, non-motile, strictly aerobic, rod shaped bacterial strain, designated CAU 1074(T), was isolated from marine sediment and its taxonomic position was investigated using a polyphasic approach. Strain CAU 1074(T) grew optimally at 30 degrees C and pH 6.5. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CAU 1074(T) formed a distinct lineage within the genus Haloferula and was most closely related to Haloferula harenae KCTC 22198(T) (96.0% similarity). Strain CAU 1074(T) contained MK-9 as the major isoprenoid quinone, and iso-C(14:0,) C(16:1)omega9c and C(16:0) as the major fatty acids. The cell wall peptidoglycan contained meso diaminopimelic acid. The major whole-cell sugars were glucose, xylose, mannose and ribose. The polar lipids were composed of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, aminoglycolipid and two unidentified phospholipids. The DNA G+C content of the strain was 64.0 mol%. On the basis of phenotypic and chemotaxonomic data, and phylogenetic inference, strain CAU 1074(T) should be classified as a member of a novel species in the genus Haloferula, for which the name Haloferula chungangensis sp. nov. is proposed; the type strain is CAU 1074(T) (= KCTC 23578(T) = CCUG 61920(T)). An emended description of the genus Haloferula is also provided. PMID- 22307511 TI - Legionella tunisiensis sp. nov. and Legionella massiliensis sp. nov., isolated from environmental water samples. AB - Two isolates of intra-amoeba-growing bacteria, LegA(T) ( = DSM 24804(T) = CSUR P146(T)) and LegM(T) ( = DSM 24805(T) = CSUR P145(T)), were characterized on the basis of microscopic appearance, staining characteristics, axenic growth at different temperatures and the sequences of the mip, rpoB, 16S rRNA and rnpb genes, as well as the 23S-5S region. Phylogenetic analysis showed that these two isolates lay within the radius of the family Legionellaceae. Furthermore, the analysis of these genes yielded congruent data that indicated that, although strain LegM(T) clusters specifically with Legionella feeleii ATCC 35072(T) and LegA(T) clusters with Legionella nautarum ATCC 49596(T), the divergence observed between these species was greater than that observed between other members of the family. Taken together, these results support the proposal that these two isolates represent novel members of the genus Legionella, and we propose to name them Legionella tunisiensis sp. nov. for LegM(T) ( = DSM 24805(T) = CSUR P145(T)) and Legionella massiliensis sp. nov. for LegA(T) ( = DSM 24804(T) = CSUR P146(T)). PMID- 22307512 TI - Differentiation and classification of phytoplasmas in the pigeon pea witches' broom group (16SrIX): an update based on multiple gene sequence analysis. AB - The pigeon pea witches'-broom phytoplasma group (16SrIX) comprises diverse strains that cause numerous diseases in leguminous trees and herbaceous crops, vegetables, a fruit, a nut tree and a forest tree. At least 14 strains have been reported worldwide. Comparative phylogenetic analyses of the highly conserved 16S rRNA gene and the moderately conserved rplV (rpl22)-rpsC (rps3) and secY genes indicated that the 16SrIX group consists of at least six distinct genetic lineages. Some of these lineages cannot be readily differentiated based on analysis of 16S rRNA gene sequences alone. The relative genetic distances among these closely related lineages were better assessed by including more variable genes [e.g. ribosomal protein (rp) and secY genes]. The present study demonstrated that virtual RFLP analyses using rp and secY gene sequences allowed unambiguous identification of such lineages. A coding system is proposed to designate each distinct rp and secY subgroup in the 16SrIX group. PMID- 22307513 TI - Advenella faeciporci sp. nov., a nitrite-denitrifying bacterium isolated from nitrifying-denitrifying activated sludge collected from a laboratory-scale bioreactor treating piggery wastewater. AB - Strain M-07(T) was isolated from nitrifying-denitrifying activated sludge treating piggery wastewater. Phylogenetic analysis based on 16S rRNA gene sequences demonstrated that strain M-07(T) belonged to the genus Advenella. 16S rRNA gene sequence similarity between M-07(T) and Advenella incenata CCUG 45225(T), Advenella mimigardefordensis DPN7(T) and Advenella kashmirensis WT001(T) was 96.5, 97.3 and 96.9%, respectively. The DNA G+C content of strain M 07(T) was 49.5 mol%, which was approximately 5 mol% lower than the range for the genus Advenella (53.5-58.0 mol%). The predominant cellular fatty acids of strain M-07(T) were C(16:0), summed feature 3 (comprising C(16:1)omega7c and/or iso C(15:0) 2-OH), C(17:0) cyclo and summed feature 2 (comprising one or more of C(14:0) 3-OH, iso-C(16:1) I, an unidentified fatty acid with an equivalent chain length of 10.928 and C(12:0) alde). The isoprenoid quinone was Q-8. On the basis of phenotypic characteristics, phylogenetic analysis and DNA-DNA relatedness, strain M-07(T) should be classified as a novel species of the genus Advenella, for which the name Advenella faeciporci sp. nov. is proposed. The type strain is M-07(T) ( = JCM 17746(T) = KCTC 23732(T)). PMID- 22307514 TI - Thermovum composti gen. nov., sp. nov., an alphaproteobacterium from compost. AB - A Gram-stain-positive thermophilic bacterium, designated strain Nis3(T), was isolated from compost. The strain grew at 23-57 degrees C (optimum, 50 degrees C); no growth was observed below 15 or above 60 degrees C. The pH range for growth was 5.9-8.8 (optimum, 7.0); no growth was observed below pH 5.4 or above pH 9.3. The DNA G+C content of strain Nis3(T) was 63.4 mol%. The dominant quinone type was ubiquinone Q-10. The major fatty acids were C(18:1)omega7c, C(19:0)omega8c cyclo and C(18:0). The polar lipids comprised phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, hydroxyphosphatidylethanolamine, phosphatidylinositol, phosphatidylmonomethylethanolamine, an unknown glycolipid and a ninhydrin-positive phospholipid. 16S rRNA gene sequence analysis assigned this bacterium to the family Phyllobacteriaceae in the Alphaproteobacteria but it shared less than 95.2% sequence similarity with other members of the family. The chemotaxonomic and phenotypic characteristics of strain Nis3(T) differed in some respects from those of members of the family Phyllobacteriaceae. Therefore, strain Nis3(T) is considered to represent a novel species of a new genus in the family Phyllobacteriaceae, for which the name Thermovum composti gen. nov., sp. nov. is proposed. The type strain is Nis3(T) ( = JCM 17863(T) = KCTC 23707(T)). PMID- 22307515 TI - Sphingomonas indica sp. nov., isolated from hexachlorocyclohexane (HCH) contaminated soil. AB - A bacterial strain, designated Dd16(T), was isolated from a hexachlorocyclohexane (HCH) dumpsite at Lucknow, India. Cells of strain Dd16(T) were Gram-stain negative, non-motile, rod-shaped and yellow-pigmented. Phylogenetic analysis based on 16S rRNA gene sequences showed that the strain belonged to the genus Sphingomonas in the family Sphingomonadaceae, as it showed highest sequence similarity to Sphingomonas asaccharolytica IFO 15499(T) (95.36 %), Sphingosinicella vermicomposti YC7378(T) (95.30), 'Sphingomonas humi' PB323 (95.20 %), Sphingomonas sanxanigenens NX02(T) (95.14%) and Sphingomonas desiccabilis CP1D(T) (95.00%). The major fatty acids were summed feature 3 (C(16:1)omega7c/C(16:1)omega6c) C(14:0) 2-OH, summed feature 8 (C(18:1)omega7c and/or C(18:1)omega6c) and C(16:0). The polar lipid profile of strain Dd16(T) also corresponded to those reported for species of the genus Sphingomonas (phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, and a sphingoglycolipid), again supporting its identification as a member of the genus Sphingomonas. The predominant respiratory quinone was ubiquinone Q(10), and sym-homospermidine was the major polyamine observed. The total DNA G+C content of strain Dd16(T) was 65.8 mol%. The results obtained on the basis of phenotypic characteristics and phylogenetic analysis and after biochemical and physiological tests, clearly distinguished strain Dd16(T) from closely related members of the genus Sphingomonas. Thus, strain Dd16(T) represents a novel species of the genus Sphingomonas for which the name Sphingomonas indica sp. nov. is proposed. The type strain is Dd16(T) ( = DSM 25434(T) = CCM 7882(T)). PMID- 22307516 TI - Nonomuraea monospora sp. nov., an actinomycete isolated from cave soil in Thailand, and emended description of the genus Nonomuraea. AB - A novel actinomycete, designated strain PT708(T), was isolated from cave soil collected in Pha Tup Cave Forest Park, Nan province, Thailand. It produced compounds with antimicrobial and anticancer activities. Its chemotaxonomic properties were consistent with those of members of the genus Nonomuraea. The major menaquinone was MK-9(H(4)), with minor amounts of MK-9(H(6)), MK-9(H(2)), MK-10(H(2)) and MK-8(H(4)). The polar lipid profile contained phosphatidylmonomethylethanolamine, diphosphatidylglycerol, hydroxy phosphatidylmonomethylethanolamine, hydroxy-phosphatidylethanolamine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol mannoside and phosphatidylinositol. The major fatty acids were iso-C(16:0), 10-methyl C(17:0), C(16:0) and C(17:1)omega6c. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain PT708(T) belonged to the genus Nonomuraea and was most closely related to Nonomuraea rhizophila YIM 67092(T) (98.50% sequence similarity) and Nonomuraea rosea GW 12687(T) (98.30%). The genomic DNA G+C content of strain PT708(T) was 73.3 mol%. Unlike the recognized members of the genus Nonomuraea, the novel strain formed single spores at the tips of aerial hyphae. Based on the phenotypic, phylogenetic and genotypic evidence, strain PT708(T) represents a novel species of the genus Nonomuraea, for which the name Nonomuraea monospora sp. nov. is proposed. The type strain is PT708(T) ( = TISTR 1910(T) = JCM 16114(T)). PMID- 22307517 TI - Halomonas beimenensis sp. nov., isolated from an abandoned saltern. AB - A Gram-staining negative, motile, non-spore-forming, short rod-shaped (0.8-1.5 * 1.5-2.0 um), halophilic bacterium, designated strain NTU-107(T), was isolated from brine samples collected from the abandoned Beimen saltern in southern Taiwan. The novel strain grew with 0-15% (w/v) NaCl (optimum between 5% and 10%), at 15-55 degrees C (optimum 40 degrees C) and at pH 5.5-9.5 (optimum pH 7.5). The major cellular fatty acids were C(18:1)omega7c, C(16:0) and C(19:0 )cyclo omega8c, the genomic DNA G+C content was 66.5 mol%, and the predominant ubiquinone was Q-9. The major polar lipids included phosphatidylglycerol, diphosphatidylglycerol and phosphatidylethanolamine. In a phylogenetic analysis based on 16S rRNA gene sequences, strain NTU-107(T) clustered with members of the genus Halomonas. In hybridization experiments, however, the levels of DNA-DNA relatedness between strain NTU-107(T) and the type strains of its closest phylogenetic neighbours (Halomonas koreensis, H. organivorans and H. ventosae) were all found to be less than 40 %. Based on the phenotypic, chemotaxonomic and genetic data, strain NTU-107(T) represents a novel species within the genus Halomonas, for which the name Halomonas beimenensis sp. nov. is proposed. The type strain is NTU-107(T) ( = BCRC 17999(T) = KCTC 22876(T) = JCM 16084(T)). PMID- 22307519 TI - Cage lifetimes of ionic liquids as studied by the magnetic field effect probe. AB - Magnetic field effects (MFEs) on the photoinduced hydrogen abstraction reaction of benzophenone with phenol were investigated in ionic liquids (ILs) with a short alkyl chain (N,N,N-trimethyl-N-propylammonium bis(trifluoromethanesulfonyl)amide (TMPA TFSA)) and long alkyl chains ((N,N,N-trimethyl-N-octylammonium bis(trifluoromethanesulfonyl)amide (TMOA TFSA) and N-decyl-N,N,N trimethylammonium bis(trifluoromethanesulfonyl)amide (DTMA TFSA)) by a nanosecond laser flash photolysis technique. In each ionic liquid, escaped radical yield of a benzophenone ketyl radical rapidly increased with increasing magnetic field strength (B) of 0 T < B<= 0.01 T. At 0.01 T < B<= 0.4 T, the escaped radical yield almost saturated in TMPA TFSA or gradually increased in TMOA TFSA and DTMA TFSA. At much higher fields of 0.4 T < B<= 30 T, the yield gradually decreased, resulting in 10-15% decrease at 30 T. The observed MFEs can be explained by the hyperfine coupling and Deltag mechanisms together with the relaxation mechanism. On the time profiles of the transient absorption observed for the benzophenone ketyl radical, MFEs were generated in the time range of 0 < t < 0.6 MUs. The cage lifetimes of TMOA TFSA and DTMA TFSA were estimated to be at least 120 ns. PMID- 22307520 TI - microRNAs in the regulation of dendritic cell functions in inflammation and atherosclerosis. AB - Atherosclerosis has been established as a chronic inflammatory disease of the vessel wall. Among the mononuclear cell types recruited to the lesions, specialized dendritic cells (DCs) have gained increasing attention, and their secretory products and interactions shape the progression of atherosclerotic plaques. The regulation of DC functions by microRNAs (miRNAs) may thus be of primary importance in disease. We here systematically summarize the biogenesis and functions of miRNAs and provide an overview of miRNAs in DCs, their targets, and potential implications for atherosclerosis, with a particular focus on the best characterized miRNAs in DCs, namely, miR-155 and miR-146. MiRNA functions in DCs range from regulation of lipid uptake to cytokine production and T cell responses with a complex picture emerging, in which miRNAs cooperate or antagonize DC behavior, thereby promoting or counterbalancing inflammatory responses. As miRNAs regulate key functions of DCs known to control atherosclerotic vascular disease, their potential as a therapeutic target holds promise and should be attended to in future research. PMID- 22307521 TI - Structural insights into a human anti-IFN antibody exerting therapeutic potential for systemic lupus erythematosus. AB - Increasing evidences suggest that the type I interferon alpha (IFN alpha) plays a critical role in the etiopathogenesis of systemic lupus erythematosus (SLE), which makes it a promising therapeutic target for the treatment of the disease. By screening a large size non-immune human antibody library, we have developed a human single-chain antibody (ScFv) AIFN alpha 1bScFv01 and corresponding whole antibody AIFN alpha 1bIgG01 to human interferon alpha 1b (IFN alpha 1b) with high specificity and high affinity. The IgG antibody could down-regulate the expression of ISG15 and IFIT-1 induced by either recombinant IFN alpha 1b or naive IFN alpha from SLE patients' sera, and reduced total serum IgG and IgM antibodies level in a pristane-primed lupus-like mouse model. The crystal structure of AIFN alpha 1bScFv01-IFN alpha 1b complex solved to 2.8 A resolution revealed that both Pro26-Gln40 region in loop AB and Glu147-Arg150 region in helix E of IFN alpha 1b contribute to binding with AIFN alpha 1bScFv01. Four residues of above two regions (Leu30, Asp32, Asp35 and Arg150) are critical for the formation of antigen-antibody complexes. AIFN alpha 1bScFv01 shares partial epitopes of IFN alpha 1b with its receptor IFNAR2 but with much higher binding affinity to IFN alpha 1b than IFNAR2. Thus, AIFN alpha 1bIgG01 exhibits its neutralizing activity through competition with IFNAR2 to bind with IFN alpha and prevents the activation of IFN alpha-mediated signaling pathway. Our results highlight the potential use of the human antibody for modulating the activity of IFN alpha in SLE. PMID- 22307523 TI - Myeloid Elf-1-like factor stimulates adipogenic differentiation through the induction of peroxisome proliferator-activated receptor gamma expression in bone marrow. AB - Myeloid Elf-1 like factor (MEF) is one of the Ets transcription factors known to regulate cell proliferation and differentiation. A previous report has shown that osteoblast-specific MEF transgenic mice (Col1a1-MEF TG mice) have low bone mass but high bone marrow adiposity. In the present study, we explored a previously unappreciated mechanism whereby MEF promotes adipogenesis in bone marrow. An adipogenic colony-forming unit assay showed that bone marrow cells derived from Col1a1-MEF TG mice had a higher adipogenic differentiation potential compared to those from wild-type. The levels of adipogenic marker genes expression in 3T3L1 cells were higher when co-cultured with Col1a1-MEF TG bone marrow cells than with wild-type cells. MC3T3-E1 preosteoblasts transfected with MEF secreted higher levels of 15-deoxy-delta (12, 14)-prostaglandin J(2), a potent endogenous ligand of peroxisome proliferator-activated receptor gamma (PPARgamma), under adipogenic conditions. MEF overexpression increased the adipogenic marker genes expression including PPARgamma and lipid droplet accumulation in MC3T3-E1 preosteoblasts and 3T3L1 preadipocytes. Endogenous MEF expression levels increased as adipocyte differentiation proceeded. Knockdown of MEF by siRNA suppressed expression levels of adipogenic marker genes including PPARgamma. MEF directly bound to the MEF binding element on the mouse PPARgamma promoter, transactivating promoter activity. Immunohistochemical staining of tibia sections demonstrated that bone lining cells and bone marrow cells express higher levels of PPARgamma protein in Col1a1-MEF TG mice than in wild-type mice. These results suggest that MEF transactivates PPARgamma expression, which, in turn, enhances adipogenic differentiation. Furthermore, MEF overexpressing osteoblasts secrete higher levels of adipogenic factors, creating a marrow microenvironment that favors adipogenesis. PMID- 22307522 TI - The E3 ubiquitin ligase TRIM11 mediates the degradation of congenital central hypoventilation syndrome-associated polyalanine-expanded PHOX2B. AB - Expansions of a polyalanine (polyA) stretch in the coding region of the PHOX2B gene cause congenital central hypoventilation syndrome (CCHS), a neurocristopathy characterized by the absence of adequate control of autonomic breathing. Expansion of polyA in PHOX2B leads to protein misfolding and accumulation into inclusions. The mechanisms that regulate mutant protein degradation and turnover have been poorly elucidated. Here, we investigate the regulation of degradation of wild-type and polyA-expanded PHOX2B. We show that expanded PHOX2B is targeted for degradation through the ubiquitin-proteasome system, resulting in lowered levels of the mutant protein relative to its wild-type counterpart. Moreover, we show that mutant PHOX2B forms ubiquitin-positive inclusions, which sequester wild type PHOX2B. This sequestration correlates with reduced transcriptional activity of endogenous wild-type protein in neuroblastoma cells. Finally, we show that the E3 ubiquitin ligase TRIM11 plays a critical role in the clearance of mutant PHOX2B through the proteasome. Importantly, clearance of mutant PHOX2B by TRIM11 correlates with a rescue of PHOX2B transcriptional activity. We propose that CCHS is partially caused by a dominant-negative effect of expanded PHOX2B due to the retention of the wild-type protein in pathogenic aggregates. Our results demonstrate that TRIM11 is a novel modifier of mutant PHOX2B toxicity and represents a potential therapeutic target for CCHS. PMID- 22307524 TI - Bioavailability of orally administered water-dispersible hesperetin and its effect on peripheral vasodilatation in human subjects: implication of endothelial functions of plasma conjugated metabolites. AB - Hesperetin is an aglycone of citrus flavonoids and is expected to exert a vasodilatation effect in vivo. We developed water-dispersible hesperetin by the process of micronization to enhance the bioavailability of hesperetin. This study aimed to assess the effect of this process on the bioavailability of hesperetin and to estimate its efficiency on vasodilatation-related functions using endothelial cells in vitro and a human volunteer study at a single dose in vivo. We found that water-dispersible hesperetin was absorbed rapidly, with its maximum plasma concentration (C(max)) being 10.2 +/- 1.2 MUM, and that the time to reach C(max), which is within 1 h if 150 mg of this preparation was orally administered in humans. LC-MS analyses of the plasma at C(max) demonstrated that hesperetin accumulated in the plasma as hesperetin 7-O-beta-D-glucuronide (Hp7GA), hesperetin 3'-O-beta-D-glucuronide (Hp3'GA) and hesperetin sulfate exclusively. Similar to hesperetin, Hp7GA enhanced nitric oxide (NO) release by inhibiting nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) activity in a human umbilical vein endothelial cell culture system, indicating that plasma hesperetin metabolites can improve vasodilatation in the vascular system. A volunteer study using women with cold sensitivity showed that a single dose of water-dispersible hesperetin was effective on peripheral vasodilatation.These results strongly suggest that rapid accumulation with higher plasma concentration enables hesperetin to exert a potential vasodilatation effect by the endothelial action of its plasma metabolites. Water-dispersible hesperetin may be useful to improve the health effect of dietary hesperetin. PMID- 22307525 TI - Effect of long-term betaine supplementation on chemical and physical characteristics of three muscles from the Alentejano pig. AB - BACKGROUND: The use of betaine as a dietary supplement to reduce fat deposition and increase lean muscle mass in pigs is increasing. However, there is no available information on its effect on the physical and chemical (i.e. fatty acid (FA) profile) characteristics of pork. RESULTS: The effects of long-term betaine intake (1 g betaine kg(-1) diet for 20 weeks) on the chemical and physical characteristics of Musculus longissimus dorsi, M. biceps femoris and M. semimembranosus from the Alentejano pig were investigated. The contents of total protein, intramuscular lipids (neutral and polar), myoglobin and total collagen as well as the water-holding capacity, physical colour characteristics and FA profile of the three muscles were determined. With the exception of a significant increase in the intramuscular lipid content of M. longissimus dorsi and M. biceps femoris, betaine supplementation did not influence muscle chemical and colour characteristics or body fat deposition. CONCLUSION: These data suggest that long term betaine supplementation selectively increases intramuscular lipid deposition (a trait related to meat quality) while not affecting other chemical (including the atheroprotective FA profile) and physical characteristics of the Alentejano pig muscles studied. PMID- 22307526 TI - MicroRNA expression abnormalities in limited cutaneous scleroderma and diffuse cutaneous scleroderma. AB - Scleroderma (systemic sclerosis, SSc) is a complex autoimmune disease caused by progressive fibrotic replacement of normal tissue architecture, a progressive and ultimately fatal process that currently has no cure. Although dysregulation of microRNAs (miRNAs) is known to be involved in a variety of pathophysiologic processes, the role of miRNAs in SSc is unclear. In comparison with the normal skin tissues, miRNAs were aberrantly expressed in limited cutaneous scleroderma and diffuse cutaneous scleroderma skin tissues. We also identified miRNAs whose expressions were correlated with SSc fibrosis: miR-21, miR-31, miR-146, miR-503, miR-145, and miR-29b were predicted to be involved. This study further confirmed that miR-21 was increased whereas miR-145 and miR-29b were decreased both in the skin tissues and fibroblasts. As predicted target genes, SMAD7, SAMD3, and COL1A1 were regulated by these miRNAs. After stimulation with transforming growth factor beta, the expression of miR-21 was increased and that of SMAD7 mRNA was decreased. MiR-145 was upregulated whereas the mRNA level of SMAD3 was downregulated. The downregulation of miR-29b was correlated with the upregulation of COL1A1 mRNA. MiRNAs might play an important role in the pathogenesis of SSc and suggest a potential therapy. PMID- 22307527 TI - Facile preparation of nitrogen-doped graphene as a metal-free catalyst for oxygen reduction reaction. AB - Nitrogen-doped graphene (nG) is a promising metal-free catalyst for oxygen reduction reaction (ORR) on the cathode of fuel cells. Here we report a facile preparation of nG via pyrolysis of graphene oxide with melamine. The morphology of the nG is revealed using scanning electron microscopy and transmission electron microscopy while the successful N doping is confirmed by electron energy loss spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy. The resulting nG shows high electrocatalytic activity toward ORR in an alkaline solution with an onset potential of -0.10 V vs. Ag/AgCl reference electrode. The nG catalyzed oxygen reduction exhibits a favorable formation of water via a four-electron pathway. Good stability and anti-crossover property are also observed, which are advantageous over the Pt/C catalyst. Furthermore, the effect of pyrolysis temperature on the structure and activity of nG is systematically studied to gain some insights into the chemical reactions during pyrolysis. PMID- 22307528 TI - Identification of blood protein biomarkers that aid in the clinical assessment of patients with malignant glioma. AB - Analyzing molecular biomarkers using blood is an important approach for clinical assessment of malignant glioma. We investigated a molecular proteomic biomarker based approach for glioblastoma using patients' blood samples. The expression levels of a list of candidate proteins were quantified in plasma and serum samples from two different cohorts of patients with malignant glioma and normal controls. The biological function was studied for one of the identified markers. Additionally, the prognostic significance of protein marker expression was measured by survival analysis. As a result, protein biomarkers associated with malignant glioma were identified from the blood specimens and five of the protein biomarkers were common to both cohorts. Immunohistochemical analysis demonstrated that many of the protein biomarkers identified in peripheral blood specimens were expressed in malignant gliomas. Staining levels for one of the biomarkers, MIP 1alpha, was found to correlate with WHO grade among invasive gliomas, and we demonstrate that MIP-1alpha promotes human glioblastoma cell proliferation and migration. Additionally, four prognostic protein biomarkers were identified. In conclusion, we demonstrate that both peripheral blood plasma and serum specimens are highly valuable and complementary to each other in the quest for protein biomarkers of malignant glioma. Sets of novel protein biomarkers were identified that may aid in the diagnosis and prognosis of patients with malignant glioma. PMID- 22307529 TI - [Clean vesical intermittent catheterization: lubrication of vesical catheter through lidocaine or gentamicine?]. AB - INTRODUCTION: The patients who undergo intermittent catheterization are at high risk of urinary tract infection. A prophylaxis method for this infection can be represented by the lubrication of urethral catheters with 0.1% gentamycin cream. This study compared the lubrication of urethral catheters with 0.1% gentamycin cream and 2% lidocaine jelly in relation to the quantitative results of the urine culture and incidence of symptomatic urinary tract infection and asymptomatic bacteriuria. MATERIAL AND METHODS: Sixteen patients, divided in groups A and B, were studied. Patients in Group A were directed to lubricate the urethral catheter with 0.1% gentamicin cream, whereas in Group B with 2% lidocaine jelly. Urine cultures and urine analysis were carried out every three weeks, for four months, for a total of 5 samples. The presence or absence of bacteria or fungi, the number of colonies and the isolated types, and the leukocyturia were evaluated. RESULTS: No significant differences in the presence of significant bacteriuria, symptomatic urinary tract infection and asymptomatic bacteriuria were found between the two groups. Escherichia coli was the most common isolated bacterium in both groups. CONCLUSIONS: The results of this study, in line with previous works, showed that the lubrication of urethral catheters with 0.1% gentamicin cream is not an effective alternative to reduce significant bacteriuria and prevent urinary infection in patients who undergo clean intermittent catheterization. PMID- 22307530 TI - [Prostate cancer unit for an optimal management of prostate cancer unit]. AB - Prostate cancer (PC) is established as one of the most important medical problems affecting the male population. PC is the most common solid neoplasm (214 cases per 1000 men) and the second most common cause of cancer death in men. Its management involves several complex issues for both clinicians and patients. An early diagnosis is necessary to implement well-balanced therapeutic options, and the correct evaluation can reduce the risk of overtreatment with its consequential adverse effects. Breast and Prostate cancers, respectively, are the most common cancers in women and in men, and different similarities have been underlined. The paradigm of the patient consulting a multidisciplinary medical team has been an established standard approach in treating breast cancer. Such multidisciplinary approach can offer the same optional care for men with PC as it does for women with breast cancer. A multidisciplinary team (MDT) comprises healthcare professionals from different disciplines whose goal of providing optimal patient care is achieved through coordination and communication with one another. A Prostate Cancer Unit is a place where men can be cared for by specialists in PC, working together within a multi-professional team. The MTD approach guarantees a higher probability for the PC patient to receive adequate information on the disease and on all possible therapeutic strategies, balancing advantages and related side effects. The future of PC patients relies on a successful multidisciplinary collaboration between experienced physicians, which can lead to important advantages in all the phases and aspects of PC management. PMID- 22307531 TI - [Combined radiologic-urologic procedure for the placement of ureteral stent in a case of bilateral iatrogenic ureteral lesion]. AB - INTRODUCTION: Iatrogenic ureteral lesions are well-known complications of abdominal and pelvic surgery. A combined radiologic-urologic approach might be necessary to repair these lesions. MATERIALS AND METHODS: A 69-year-old woman underwent bilateral hysteroannessectomy for endometrial cancer. She then became anuric. A CT scan showed multiple urinomas caused by bilateral ureteral lesions. The continuity of the two urinary tracts was restored using ureteral stents in a combined urologic and radiologic procedure. RESULTS: The patient improved clinically and the renal function returned within normal limits. CONCLUSIONS: The combined antegrade-retrograde approach is an effective technique to solve iatrogenic ureteral lesions. PMID- 22307532 TI - Effects of 1:1, 1:2 or 1:3 intra-aortic balloon counterpulsation/heart support on coronary haemodynamics and cardiac contractile efficiency in an animal model of myocardial ischaemia/reperfusion. AB - OBJECTIVES: The effects of operational modes of intra-aortic balloon pumping (IABP) on coronary haemodynamics and oxygen delivery/demand ratio are unknown and were investigated in an experimental model of myocardial ischaemia reperfusion. METHODS: Healthy swine (n = 24) underwent 120-minute ligation of the left anterior descending coronary artery followed by 24 h of reperfusion and were randomly assigned to have IABP 1:1 (n = 6), IABP 1:2 (n = 6), IABP 1:3 (n = 6) in the descending aorta or to no IABP implantation (n = 6) 5 min after the onset of reperfusion. Systolic (CBF(Sys)) and diastolic (CBF(Dia)) coronary blood flow, systolic (CR(Sys)) and diastolic (CR(Dia)) coronary resistances and endocardial viability ratio (EVR), as an expression of the oxygen delivery/demand ratio, were measured at 30 min, 1, 6, 12 and 24 h after coronary reperfusion, respectively. RESULTS: IABP at the 1:1 operational mode significantly increased CBF(Dia) and EVR, and reduced CR(Dia) throughout the experiment. Contrastingly, IABP at 1:3 mode resulted in a significant reduction in CBF(Dia), in a steady increase in CR(Dia), in a steady reduction in O(2) delivery and a constant increase in O(2) demand over time. IABP at the 1:2 mode had no overall effect on assessed parameters. CONCLUSIONS: IABP at the 1:1 mode enhanced coronary haemodynamics and cardiac contractile efficiency in an acute animal model of coronary ischaemia/reperfusion. On the contrary, IABP support set at the 1:2 or 1:3 modes failed to provide benefit. Progressive reduction in balloon inflation with a 1:1 mode instead of decreasing the heart/IABP operational ratio might represent a better IABP withdrawal protocol and is currently under investigation. PMID- 22307533 TI - 18F-Fluoromisonidazole positron emission tomography may differentiate glioblastoma multiforme from less malignant gliomas. AB - PURPOSE: Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and its prognosis is significantly poorer than those of less malignant gliomas. Pathologically, necrosis is one of the most important characteristics that differentiate GBM from lower grade gliomas; therefore, we hypothesized that (18)F fluoromisonidazole (FMISO), a radiotracer for hypoxia imaging, accumulates in GBM but not in lower grade gliomas. We aimed to evaluate the diagnostic value of FMISO positron emission tomography (PET) for the differential diagnosis of GBM from lower grade gliomas. METHODS: This prospective study included 23 patients with pathologically confirmed gliomas. All of the patients underwent FMISO PET and (18)F-fluorodeoxyglucose (FDG) PET within a week. FMISO images were acquired 4 h after intravenous administration of 400 MBq of FMISO. Tracer uptake in the tumor was visually assessed. Lesion to normal tissue ratios and FMISO uptake volume were calculated. RESULTS: Of the 23 glioma patients, 14 were diagnosed as having GBM (grade IV glioma in the 2007 WHO classification), and the others were diagnosed as having non-GBM (5 grade III and 4 grade II). In visual assessment, all GBM patients showed FMISO uptake in the tumor greater than that in the surrounding brain tissues, whereas all the non-GBM patients showed FMISO uptake in the tumor equal to that in the surrounding brain tissues (p <= 0.001). One GBM patient was excluded from FDG PET study because of hyperglycemia. All GBM patients and three of the nine (33%) non-GBM patients showed FDG uptake greater than or equal to that in the gray matter. The sensitivity and specificity for diagnosing GBM were 100 and 100% for FMISO, and 100 and 66% for FDG, respectively. The lesion to cerebellum ratio of FMISO uptake was higher in GBM patients (2.74 +/- 0.60, range 1.71-3.81) than in non-GBM patients (1.22 +/- 0.06, range 1.09-1.29, p <= 0.001) with no overlap between the groups. The lesion to gray matter ratio of FDG was also higher in GBM patients (1.46 +/- 0.75, range 0.91-3.79) than in non-GBM patients (1.07 +/- 0.62, range 0.66-2.95, p <= 0.05); however, overlap of the ranges did not allow clear differentiation between GBM and non-GBM. The uptake volume of FMISO was larger in GBM (27.18 +/- 10.46%, range 14.02-46.67%) than in non-GBM (6.07 +/- 2.50%, range 2.12-9.22%, p <= 0.001). CONCLUSION: These preliminary data suggest that FMISO PET may distinguish GBM from lower grade gliomas. PMID- 22307534 TI - Comment on Reyes et al.: Myocardial perfusion scintigraphy in Europe 2007: a survey of the European Council of Nuclear Cardiology. PMID- 22307535 TI - Female sex pheromone and male behavioral responses of the bombycid moth Trilocha varians: comparison with those of the domesticated silkmoth Bombyx mori. AB - Analysis of female sex pheromone components and subsequent field trap experiments demonstrated that the bombycid moth Trilocha varians uses a mixture of (E,Z) 10,12-hexadecadienal (bombykal) and (E,Z)-10,12-hexadecadienyl acetate (bombykyl acetate) as a sex pheromone. Both of these components are derivatives of (E,Z) 10,12-hexadecadienol (bombykol), the sex pheromone of the domesticated silkmoth Bombyx mori. This finding prompted us to compare the antennal and behavioral responses of T. varians and B. mori to bombykol, bombykal, and bombykyl acetate in detail. The antennae of T. varians males responded to bombykal and bombykyl acetate but not to bombykol, and males were attracted only when lures contained both bombykal and bombykyl acetate. In contrast, the antennae of B. mori males responded to all the three components. Behavioral analysis showed that B. mori males responded to neither bombykal nor bombykyl acetate. Meanwhile, the wing fluttering response of B. mori males to bombykol was strongly inhibited by bombykal and bombykyl acetate, thereby indicating that bombykal and bombykyl acetate act as behavioral antagonists for B. mori males. T. varians would serve as a reference species for B. mori in future investigations into the molecular mechanisms underlying the evolution of sex pheromone communication systems in bombycid moths. PMID- 22307538 TI - Reactions of N(3) -substituted amidrazones with cis-1,2-cyclohexanedicarboxylic anhydride and biological activities of the products. AB - A series of novel compounds were synthesized in reactions of N(3) -substituted amidrazones with cis-1,2-cyclohexanedicarboxylic anhydride: linear, isoindole, and triazole derivatives. All new structures were confirmed by H(1) NMR and IR spectrometry as well as elemental analysis. Potential biological effects of new compounds were predicted with the Prediction of Activity Spectra for Substances (PASS) program. Antiviral, antibacterial, analgesic, and anti-inflammatory activities were experimentally verified. PMID- 22307539 TI - Antioxidant activity of peptide-based angiotensin converting enzyme inhibitors. AB - Angiotensin converting enzyme (ACE) inhibitors are important for the treatment of hypertension as they can decrease the formation of vasopressor hormone angiotensin II (Ang II) and elevate the levels of vasodilating hormone bradykinin. It is observed that bradykinin contains a Ser-Pro-Phe motif near the site of hydrolysis. The selenium analogues of captopril represent a novel class of ACE inhibitors as they also exhibit significant antioxidant activity. In this study, several di- and tripeptides containing selenocysteine and cysteine residues at the N-terminal were synthesized. Hydrolysis of angiotensin I (Ang I) to Ang II by ACE was studied in the presence of these peptides. It is observed that the introduction of L-Phe to Sec-Pro and Cys-Pro peptides significantly increases the ACE inhibitory activity. On the other hand, the introduction of L Val or L-Ala decreases the inhibitory potency of the parent compounds. The presence of an L-Pro moiety in captopril analogues appears to be important for ACE inhibition as the replacement of L-Pro by L-piperidine 2-carboxylic acid decreases the ACE inhibition. The synthetic peptides were also tested for their ability to scavenge peroxynitrite (PN) and to exhibit glutathione peroxidase (GPx)-like activity. All the selenium-containing peptides exhibited good PN scavenging and GPx activities. PMID- 22307540 TI - Mechanical embolectomy for treatment of large vessel acute ischemic stroke in children. AB - BACKGROUND AND PURPOSE: The three largest adult stroke trials investigating mechanical embolectomy retrieval devices in acute stroke (the Merci, Multi Merci and Penumbra Pivotal Stroke Trials) excluded children. There is a need to expand the literature on mechanical embolectomy in large vessel pediatric arterial ischemic stroke. This paper reports the use of two mechanical embolectomy devices cleared by the Federal Drug Administration (FDA) in four consecutive cases. METHODS: Our pediatric stroke database from 2002 to the present was reviewed retrospectively. Patients were included if they were diagnosed with an acute large vessel occlusion, were <18 years of age and underwent recanalization with a device cleared by the FDA. Clinical and radiographic results were abstracted from medical record review. The Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score at presentation and at discharge and a pediatric-modified Rankin Scale (Ped-mRS) at approximately 90 days were scored retrospectively based on documented examinations. RESULTS: Four patients aged 4-17 years with a PedNIHSS score at presentation ranging from 2 to 17 points underwent mechanical embolectomy for reperfusion of the basilar artery (n=3), M1 segment of the right middle cerebral artery (n=1) and right internal carotid artery terminus (n=1). Thrombolysis in cerebral infarction (TICI) grade 3 was achieved in four vessels and TICI grade 2A was achieved in one vessel; there was one asymptomatic intraparenchymal hemorrhage. Intra-arterial tissue plasminogen activator was administered in two vessels. The PedNIHSS score at discharge ranged from 0 to 16 points and the Ped-mRS score at approximately 90 days ranged from 0 to 3 with 75% achieving a Ped-mRS score of <=2. CONCLUSION: Mechanical embolectomy using the Merci and Penumbra systems may be a feasible therapeutic option in the treatment of large vessel pediatric arterial ischemic stroke. PMID- 22307541 TI - Growth and mineral acquisition response of grapevine rootstocks (Vitis spp.) to inoculation with different strains of plant growth-promoting rhizobacteria (PGPR). AB - BACKGROUND: Effects of the plant growth-promoting rhizobacteria (PGPR) strains Burkholderia gladii BA-7, Bacillus subtilis OSU-142, Bacillus megatorium M-3 and Azospirillum brasilense Sp 245 on vegetative development and mineral uptake of 1103 P and 41 B grapevine rootstocks were investigated. The roots of nursery plants of the grapevine rootstocks were immersed in bacterial solutions and transplanted to a sterilised peat and perlite mixture in 5 L pots. Plants were cultivated in a semi-controlled glasshouse during the vegetation period. RESULTS: Vegetative development of grapevine rootstocks was obviously promoted by bacterial inoculation, with the maximum increase induced by Sp 245. Inoculation with Sp 245 also significantly improved the chlorophyll concentrations of the leaves of the two rootstocks. Among the bacteria, OSU-142 also significantly stimulated vegetative development and mineral acquisition of the plants. Nutrient contents of the leaf blades of the plants were generally higher than those of control plants. CONCLUSION: Overall investigations revealed that A. brasilense Sp 245 and B. subtilis OSU-142 performed more efficiently than the other strains. Therefore these bacteria seem to have considerable potential in reducing the need for inorganic fertiliser. PMID- 22307542 TI - Formation of methanol from methane and water in an electrical discharge. AB - Matrix isolation FTIR experiments have shown that methanol is a major product when argon gas doped with water and methane is exposed to an electrical discharge and condensed to a solid matrix at 11 K. Experiments with (2)H, (17)O and (18)O labeled isotopologues show the mechanism for the methanol production is likely to be insertion of an excited oxygen atom in the (1)D state into a C-H bond of a methane molecule. In light of these experiments, the possibility of oxygen atom insertion into methane should be considered as a possible mechanism for the production of methanol in interstellar ices. PMID- 22307543 TI - Temperature dependent spectral properties of type-I and quasi type-II CdSe/CdS dot-in-rod nanocrystals. AB - We investigated systematically the temperature dependence of the spectral properties such as the band gap, bandwidth and fluorescence intensity of CdSe/CdS dot-in-rod nanocrystals. These asymmetry nanoparticles were synthesized by seeded growth techniques with band alignment of the type-I and quasi type-II with initial core sizes of 3.3 and 2.3 nm, respectively. With increasing temperature the band gap decreases and bandwidth increases, largely due to exciton-phonon scattering. Anomalous variations of the band gap and bandwidth were observed at 200-240 K, and the variations are attributed to the anisotropic strain in the CdSe/CdS interface due to temperature dependent lattice mismatch. The integrated intensity of fluorescence shows two variation regimes. In the low temperature regime, the intensity remained roughly constant due to the temperature dependent carrier mobility and trapping by the defect states in the CdS shell. However, in the higher temperature regime, the intensity decreased quickly due to thermal/phonon assisted escape from the CdSe dot. The barrier depths are estimated to be about 557 and 285 meV for type-I and quasi type-II samples, respectively. PMID- 22307544 TI - PI3K-independent AKT activation in cancers: a treasure trove for novel therapeutics. AB - AKT/PKB serine threonine kinase, a critical signaling molecule promoting cell growth and survival pathways, is frequently dysregulated in many cancers. Although phosphatidylinositol-3-OH kinase (PI3K), a lipid kinase, is well characterized as a major regulator of AKT activation in response to a variety of ligands, recent studies highlight a diverse group of tyrosine (Ack1/TNK2, Src, PTK6) and serine/threonine (TBK1, IKBKE, DNAPKcs) kinases that activate AKT directly to promote its pro-proliferative signaling functions. While some of these alternate AKT activating kinases respond to growth factors, others respond to inflammatory and genotoxic stimuli. A common theme emerging from these studies is that aberrant or hyperactivation of these alternate kinases is often associated with malignancy. Consequently, evaluating the use of small molecular inhibitors against these alternate AKT activating kinases at earlier stages of cancer therapy may overcome the pressing problem of drug resistance surfacing especially in patients treated with PI3K inhibitors. PMID- 22307545 TI - The health profile and chronic diseases comorbidities of US-bound Iraqi refugees screened by the International Organization for Migration in Jordan: 2007-2009. AB - More than 63,000 Iraqi refugees were resettled in the United States from 1994 to 2010. We analyzed data for all US-bound Iraqi refugees screened in International Organization for Migration clinics in Jordan during June 2007-September 2009 (n = 18,990), to describe their health profile before arrival in the United States. Of 14,077 US-bound Iraqi refugees >= 15 years of age, one had active TB, 251 had latent TB infection, and 14 had syphilis. No HIV infections were reported. Chronic diseases comorbidities accounted for a large burden of disease in this population: 35% (n = 4,105) of screened Iraqi refugees had at least one of three chronic medical conditions; hypertension, diabetes mellitus, or obesity. State health departments and clinicians who screen refugees need to be aware of the high prevalence of chronic diseases among Iraqi refugees resettled in the United States. These results will help public health specialists develop policies to reduce morbidity and mortality among US-bound Iraqi refugees. PMID- 22307546 TI - Extreme behavioral lateralization and the remodeling of the distal humerus. AB - OBJECTIVES: The effects of extreme behavioral lateralization (i.e., extreme handedness) on the epicondylar breadth are poorly understood. This study was conducted in order to determine the effects of high levels of right- and left handedness on epicondyle of the humerus. METHODS: Elbow width of 186 healthy male university students who completed their physical development (extreme left handed = 92, mean age = 18.67, SD = 0.61; extreme right handed = 94, mean age = 18.55, SD = 0.58) were measured with 0.01 mm sensitivity and Edinburgh Handedness Inventory was applied to determine the handedness of the individuals. Participants with scores of +100 were designated as extreme right-handers, and participants with scores of -100 were designed as extreme left-handers. RESULTS: According to the findings, the degree of directional asymmetry was +1.22 (SD = 2.24) in the extreme right handed, whereas in extreme left handed -0.59 (SD = 1.74). The relative deviation percentage in the extreme right handed was 3.1% whereas 2.2% in the extreme left handed. CONCLUSIONS: It could be stated that extreme handedness has an influence on the asymmetry of epicondyle of the humerus; nevertheless, this effect is more significant in the extreme right handed. This is likely to result from the necessity for left-handed people to adapt themselves to the conditions of a dominantly "right-handed" world. PMID- 22307547 TI - Non-curative gastric resection for patients with stage 4 gastric cancer--a single center experience and current review of literature. AB - PURPOSE: The majority of patients with gastric cancer present with an advanced stage and, therefore, may not be eligible for curative treatment. The role of non curative gastric resection in situations other than emergency treatment for life threatening tumor-related complications is still under discussion. METHODS: Data from 290 consecutive patients with advanced gastric cancer who were treated in our hospital were analyzed. A total of 48 patients underwent primary non-curative gastric resection. RESULTS: The overall survival in the non-curatively resected group was 15 months and 6 months for non-resected patients, respectively (p < 0.001). The incidence of tumor-related complications which required intervention was 63% in non-resected patients as compared to 12% in patients who underwent primary non-curative resection. Younger age, less than three tumor locations, and chemotherapy have been identified as prognostic factors for improved survival by univariate analysis. D3 lymph node involvement and chemotherapy were independent prognostic factors in the multivariate analysis. Peritoneal carcinosis did not significantly influence survival in resected patients. Non-curative resection in combination with chemotherapy resulted in longer overall survival than resection alone. CONCLUSIONS: Primary non-curative gastric resection can reduce the incidence of severe tumor-related complications and can prolong overall survival in selected subgroups. In particular, younger patients with no more than two tumor locations should be considered for this procedure. PMID- 22307548 TI - Identification of novel DNA-binding proteins using DNA-affinity chromatography/pull down. AB - This units presents methods through which one may isolate and identify novel bacterial DNA-binding proteins. Briefly, the DNA sequence of interest is affixed to beads, and then incubated with bacterial cytoplasmic extract. Washes with buffers containing nonspecific DNA and low-salt concentrations will remove non adhering and low-specificity DNA-binding proteins, while subsequent washes with higher salt concentrations will elute more specific DNA-binding proteins. Eluted proteins may then be identified by standard proteomic techniques. PMID- 22307549 TI - Laboratory maintenance of Agrobacterium. AB - Agrobacterium species are plant-associated relatives of the rhizobia. Several species cause plant diseases such as crown gall and hairy root, although there are also avirulent species. A. tumefaciens is the most intensively studied species and causes crown gall, a neoplastic disease that occurs on a variety of plants. Virulence is specified by large plasmids, and in the case of A. tumefaciens this is called the Ti (tumor-inducing) plasmid. During pathogenesis, virulent agrobacteria copy a segment of the Ti plasmid and transfer it to the plant, where it subsequently integrates into the plant genome and expresses genes that result in the disease symptoms. A. tumefaciens has been used extensively as a plant genetic engineering tool, and is also a model microorganism that has been well studied for host-microbe associations, horizontal gene transfer, cell-cell communication, and biofilm formation. This unit describes standard protocols for laboratory cultivation of A. tumefaciens. PMID- 22307550 TI - Cell culture assay for transient replication of human and animal papillomaviruses. AB - This unit contains protocols for evaluation of replication functionality of papillomavirus genomes or subgenomic fragments. Replication is measured after transient cotransfection of the genome (or subgenomic fragment) with expression vectors encoding the viral E1 and E2 proteins. Input DNA is methylated at the adenine of GATC sequences by propagation in E. coli. DNA that replicates in mammalian cells will lose the adenine methylation and become DpnI-resistant, while residual methylated input DNA will remain DpnI-sensitive. After transfection, DNA extraction, and DpnI digestion, replicated DNA can be detected by Southern blotting as a full-length plasmid, since it is resistant to digestion. This assay can be used to map the genomic location of a functional origin or to evaluate replication activity of mutations in either the origin DNA sequences or the E1 or E2 proteins. PMID- 22307551 TI - Human cytomegalovirus: bacterial artificial chromosome (BAC) cloning and genetic manipulation. AB - The understanding of human cytomegalovirus (HCMV) biology was long hindered by the inability to perform efficient viral genetic analysis. This hurdle was recently overcome when the genomes of multiple HCMV strains were cloned as infectious bacterial artificial chromosomes (BACs). The BAC system takes advantage of the single-copy F plasmid of E. coli that can stably carry large pieces of foreign DNA. In this system, a recombinant HCMV virus carrying a modified F plasmid is first generated in eukaryotic cells. Recombinant viral genomes are then isolated and recovered in E. coli as BAC clones. BAC-captured viral genomes can be manipulated using prokaryotic genetics, and recombinant virus can be reconstituted from BAC transfection in eukaryotic cells. The BAC reverse genetic system provides a reliable and efficient method to introduce genetic alterations into the viral genome in E.coli and subsequently analyze their effects on virus biology in eukaryotic cells. PMID- 22307552 TI - Bluetongue virus (BTV): propagation, quantification, and storage. AB - As an obligate intracellular parasite, the genome of the Bluetongue virus (BTV) contains ten double-stranded RNA segments which are encapsidated by viral proteins, forming "transport vesicles" that can transmit the viral progeny cell to-cell efficiently and that can also be transmitted animal-to-animal by a biting midge. BTV is a cytoplasmic virus, and its five major steps of viral infection: attachment, entry, uncoating, assembly, and release, occur only in the cytosol within the infected host cell. Viral replication, suppression of cellular processes, and subsequent pathological damage disrupt many cellular pathways, leading to cellular apoptosis. All of these steps are under very rapid, tight, and efficient control. BTV infects both domestic and wild ruminants, especially sheep, but not humans. BTV is also the prototype in the Orbivirus genus of the Reoviridae family, and has been studied very extensively for the last 25 years. The experimental protocols presented here describe most of the methods that have been used routinely and reproducibly in our lab for our studies of the BTV biosystems. PMID- 22307553 TI - Laboratory maintenance of Helicobacter species. AB - Helicobacter species are Gram-negative bacteria that colonize the gastric or intestinal mucosa of many mammalian and avian hosts and induce histologic inflammation. The association of H. pylori with gastritis, peptic ulcer disease, and gastric cancers makes it a significant human pathogen. Animal models for these diseases are being used to explore the pathogenesis of H. pylori infection and in vaccine development. Both bacterial and host factors contribute to Helicobacter pathogenesis; therefore, the microbiology is very important. This unit describes how to culture the most commonly used gastric Helicobacter species, H. pylori, H. mustelae, and H. felis. PMID- 22307554 TI - High-throughput clonal analysis of neural stem cells in microarrayed artificial niches. AB - To better understand the extrinsic signals that control neural stem cell (NSC) fate, here we applied a microwell array platform which allows high-throughput clonal analyses of NSCs, cultured either as neurospheres or as adherent clones, exposed to poly(ethylene glycol) (PEG) hydrogel substrates functionalized with selected signaling molecules. We analyzed by time-lapse microscopy and retrospective immunostaining the role of integrin and Notch ligands, two key NSC niche components, in altering the behavior of several hundred single stem cells isolated from a previously described Hes5::GFP reporter mouse. NSC self-renewal was increased by 1.5-fold upon exposure to covalently tethered Laminin-1 and fibronectin fragment 9-10 (FN(9-10)), where 60-65% of single cells proliferated extensively and remained Nestin positive. Tethering of the Notch ligand Jagged-1 induced activation of Notch signaling. While Jagged-1 alone increased cell survival and proliferation, no further increase in the clonogenic potential of Hes5::GFP cells was observed upon co-stimulation with Laminin-1 and Jagged-1. We believe that the bioengineering of such in vitro niche analogues is a powerful approach to elucidate single stem cell fate regulation in a well-controlled fashion. PMID- 22307555 TI - Comparative mapping of the oat Dw6/dw6 dwarfing locus using NILs and association with vacuolar proton ATPase subunit H. AB - Seven pairs of oat near-isogenic lines (NILs) (Kibite in Crop Sci 41:277-278, 2001) contrasting for the Dw6 dwarfing gene were used to test for correlation between tall/dwarf phenotype and polymorphic genotype using restriction fragment length polymorphism (RFLP) and other molecular markers selected from the Kanota * Ogle (K*O) (Wight et al. in Genome 46:28-47, 2003) and Terra * Marion (De Koeyer et al. in Theor Appl Genet 108:1285-1298, 2004) recombination maps. This strategy located the Dw6/dw6 locus to a small chromosomal region on K*O linkage group (LG) KO33, near or at a putative RFLP locus aco245z. Aco245z and other tightly linked flanking markers have potential for use in marker-assisted selection (MAS), and PCR-based markers were developed from several of these. RFLP genotyping of the Dw6 NILs indicated that 13 of the 14 individual lines were homogeneously maternal or paternal for a large genomic region near Dw6/dw6, an unexpected result for NILs. The cDNA clone aco245 codes for a vacuolar proton ATPase subunit H, a potential candidate gene for Dw6. Vacuolar proton ATPase enzymes have a central role in plant growth and development and a mutation in subunit C is responsible for the det3 dwarfing mutation in Arabidopsis thaliana (Schumacher et al. in Genes Dev 13:3259-3270, 1999). Aco245 affords the potential of designing highly precise diagnostic markers for MAS for Dw6. The Dw6 NILs have potential utility to investigate the role of vacuolar proton ATPases in growth and development in plants. PMID- 22307556 TI - Improvement in health-related quality of life in MPO-ANCA-associated vasculitis patients treated with cyclophosphamide plus prednisolone: an analysis of 18 months of follow-up data from the JMAAV study. AB - OBJECTIVES: To examine the improvement in health-related quality of life (HRQOL) in association with disease activity in myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis patients treated with cyclophosphamide plus prednisolone. METHODS: According to the Japanese Patients with MPO-ANCA-Associated Vasculitis (JMAAV) study protocol, a total of 48 patients with newly diagnosed MPO-ANCA-associated vasculitis received a standardized cyclophosphamide plus prednisolone regimen, and their clinical courses were followed for 18 months following their entry into the study. Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS) 2003. HRQOL was assessed using MOS Short-Form 36 (SF-36) v2. BVAS new/worse, BVAS persistent, and SF-36 domain scores (norm-based) were calculated for the 32 eligible patients. RESULTS: The mean SF-36 domain scores were significantly lower than the Japanese general population norm. Stepwise multiple linear regression analysis showed that the presence of new or worsening features of the nervous system was significantly associated with a deterioration in physical function. During the 18 months of follow-up, there were significant improvements in BVAS new/worse and all SF-36 domains except for general health and role emotional. CONCLUSION: MPO-ANCA-associated vasculitis patients experienced a considerable deterioration in HRQOL. The standardized cyclophosphamide plus prednisolone regimen of the JMAAV study induced remission in the majority of patients, and the induction of remission accompanied a recovery in HRQOL. PMID- 22307557 TI - Structural analysis of the EGFR TK domain and potential implications for EGFR targeted therapy. AB - The development and clinical application of TK domain inhibitors (TKIs) provide important insights into the broader field of cancer-targeted therapies. To discuss the recent advances in the atomic level understanding of EGFR TK domain mutations, we aim at highlighting the current and future importance of these studies on malignancies where the TK domain is improperly activated. The analysis is conducted on published TK domain crystal structures deposited in the Protein Data Bank, or homology structures generated by homology modeling and AutoDock 4.2 software using the program O. Mutations in exon 19 are the most common pathogenic mutations, so the crystal structures with these mutations are analyzed and compared in detail. In addition, we demonstrate how these crystal structures of EGFR conformation with TK domain mutations and those binding with small molecule inhibitors unveil the active or inactive mechanisms. As to the increasing resistance to the TKI, we summarize the progress on overcoming this challenge. Simultaneously, we predict the structure of BIKW-2992 binding to EGFR and compare it with the validated structure of HKI-272. It is hoped that a more accurate resistance mechanism would be found. In brief, we believe that this research will provide insights into EGFR targeted therapies. PMID- 22307558 TI - Postoperative spondilodiscitis. AB - INTRODUCTION: Postoperative spondylodiscitis is a primary infection of the nucleus pulposus with secondary involvement of the cartilaginous endplate and vertebral bone. Although uncommon, postoperative spondylodiscitis causes major morbidity and may be associated with serious long-term sequelae. Several risk factors had been identified, including immunosuppression, obesity, alcohol, smoking, diabetes and malnutrition. MATERIALS AND METHODS: A review of the literature was done to analyse the diagnosis, treatment and prevention of postoperative spondylodiscitis. RESULTS: We found that the principles of conservative treatment are to establish an accurate microbiological diagnosis, treat with appropriate antibiotics, immobilise the spine, and closely monitor for spinal instability and neurological deterioration. The purpose of surgical treatment is to obtain multiple cultures of bone and soft tissue, perform a thorough debridement of infected tissue, decompress neural structures, and reconstruct the unstable spinal column with bone graft with or without concomitant instrumentation. CONCLUSIONS: Appropriate management requires aggressive medical treatment and, at times, surgical intervention. If recognised early and treated appropriately, a full recovery can often be expected. Therefore, clinicians should be aware of the clinical presentation of such infections to improve patient outcome. A review of the literature was done to advance our understanding of the diagnosis, treatment, prevention and outcome of these infections. PMID- 22307559 TI - Distal metaphyseal radius fractures in children following closed reduction and casting: can loss of reduction be predicted? AB - PURPOSE: The aim of this study was to identify factors which contribute to loss of reduction (LOR). METHODS: Outpatient records and initial, post-reduction (PR) and follow-up radiographs of patients with a distal radial metaphyseal fracture were reviewed to determine demographic factors; fracture characteristics (obliquity, comminution, intact ulna); three-point cast index (3PI); and initial, PR, and follow-up displacement (angulation and translation in the sagittal and coronal planes). Univariate and multivariate regression were used to identify significant risk factors for LOR. RESULTS: A total of 161 patients were included in our series (119 boys and 42 girls). Fifty-seven (35%) patients met the criteria for LOR. Multivariate logistic regression revealed that patients over 14 years old were 4.8 times more likely (p=0.01) to lose reduction, and those with more than 10% PR translation in the sagittal plane were four times more likely (p=0.03) to lose reduction. In younger patients, initial coronal translation and PR sagittal translation were independent risk factors. Patients with over 10% initial translation in the coronal plane were 2.4 times more likely (p=0.01) to lose reduction, and those with over 10% PR translation in the sagittal plane were 2.7 times more likely (p=0.03) to lose reduction. Three point cast index was not found to be a significant risk factor (1.64 vs. 1.57, p=0.43). CONCLUSION: Our study, the largest dedicated series of distal radial metaphyseal fractures, indicates that loss of reduction is common. Our analysis suggests that an anatomical reduction, which minimises residual translation, is the most important variable in preventing a loss of reduction. PMID- 22307560 TI - Retrograde dynamic locked nailing for valgus knee correction: a revised technique. AB - PURPOSE: Traditionally, valgus knee deformity is predominately corrected by stabilisation with a plate inserted via the medial approach to the supracondylar region of the femur. However, this technique is unfavourable from both a biomechanical and a biological point of view. A revised retrograde dynamic locked nailing was developed to improve correction of this defect. METHOD: Forty-one knees with valgus deformity (average tibiofemoral angle, 22 degrees ; range, 16 29 degrees ) in 25 adult patients were treated by oblique femoral supracondylar varus osteotomy and stabilised with retrograde dynamic locked nails. Postoperatively, early ambulation with protected weight bearing and range of motion knee exercises were encouraged. RESULT: Thirty-five knees of 21 patients were followed-up for an average of 2.6 years (range, 1.1-4.5 years). All osteotomy sites healed with an average union period of 3.4 months (range, 2.5-5.0 months). There were no significant complications. At the latest follow-up, the average tibiofemoral angle was 7.1 degrees valgus (range, 4-10 degrees valgus). For all of the knees, the outcomes were satisfactory (p < 0.001). CONCLUSION: The technique described here may be a feasible alternative for correction of valgus knee deformity. The advantages of this technique include the use of a biomechanically more appropriate method, a minimal complication rate and a high rate of satisfactory outcomes. PMID- 22307561 TI - Metal-organic frameworks constructed from versatile [WS4Cu(x)](x-2) units: micropores in highly interpenetrated systems. AB - Five metal-organic frameworks (MOFs) formed by [WS(4)Cu(x)](x-2) secondary building units (SBUs) and multi-pyridyl ligands are presented. The [WS(4)Cu(x)](x 2) SBUs function as network vertexes showing various geometries and connectivities. Compound 1 contains one-dimensional channels formed in fourfold interpenetrating diamondoid networks with a hexanuclear [WS(4)Cu(5)](3+) unit as SBU, which shows square-pyramidal geometry and acts as a tetrahedral node. Compound 2 contains brick-wall-like layer also with a hexanuclear [WS(4)Cu(5)](3+) unit as SBU. The [WS(4)Cu(5)](3+) unit in 2 is a new type of [WS(4)Cu(x)](x-2) cluster unit in which the five Cu(+) ions are in one plane with the W atom, forming a planar unit. Compound 3 shows a nanotubular structure with a pentanuclear [WS(4)Cu(4)](2+) unit as SBU, which is saddle-shaped and acts as a tetrahedral node. Compound 4 contains large cages formed between two interpenetrated (10,3)-a networks also with a pentanuclear [WS(4)Cu(4)](2+) unit acting as a triangular node. The [WS(4)Cu(4)](2+) unit in 4 is isomeric to that in 3 and first observed in a MOF. Compound 5 contains zigzag chains with a tetrahedral [WS(4)Cu(3)](+) unit as SBU, which acts as a V-shaped connector. The influence of synthesis conditions including temperature, ligand, anions of Cu(I) salts, and the ratio of [NH(4)](2)WS(4) to Cu(I) salt on the formation of these [WS(4)Cu(x)](x-2)-based MOFs were also studied. Porous MOF 3 is stable upon removal and exchange of the solvent guests, and when accommodating different solvent molecules, it exhibits specific colors depending on the polarity of incorporated solvent, that is, it shows a rare solvatochromic effect and has interesting prospects in sensing applications. PMID- 22307562 TI - Design, synthesis, and biological evaluation of bromophenol derivatives as protein tyrosine phosphatase 1B inhibitors. AB - 3-Bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol (BDB) is a bromophenol purified from the marine red alga Rhodomela confervoides and exhibits potent protein tyrosine phosphatase 1B (PTP1B) inhibition (IC(50) = 1.7 umol/L). In an effort to improve the PTP1B inhibitory activity, a series of derivatives were designed, synthesized, and evaluated in vitro. The preliminary structure activity relationship indicated that the tricyclic scaffold and multi-bromine atoms (four to five) attached to the aryl rings are important for PTP1B inhibition. Among these, compound 26 exhibited remarkable inhibitory activity against PTP1B with an IC(50) of 0.89 umol/L, which was approximately two-fold more potent than the initial lead compound BDB. PMID- 22307563 TI - New directions in reducing stress effects on cancer. AB - A growing body of evidence is now connecting neuroendocrine mediators of the stress response to cancer biology. Al-Wadei and colleagues report a study in this issue of the journal (beginning on page 189) that provides a new piece of this evidence, adding the inhibitory neurotransmitter gamma-aminobutyric acid to this intricate pathway. Their mouse model study supports the hypothesis that stress mediators contribute to lung cancer progression and that known inhibitors of the stress pathway might block such effects, thus adding to the impetus for studying cancer prevention strategies targeting the stress pathway. PMID- 22307565 TI - Notes from the field: "green" chemoprevention as frugal medicine. AB - Prevention trials of whole foods or simple extracts offer prospects for reducing an expanding global burden of cancer effectively, and in contrast to promising isolated phytochemicals or pharmaceuticals, frugally. We use the term "green" chemoprevention to differentiate a food-centered approach that is sustainable in underserved populations. It can be applied to personalized medicine just as well as a pharmaceutical approach, but only green chemoprevention can be applied in both rich and poor settings. This MiniReview discusses some of the challenges of conducting food-based trials in developing countries, with particular emphasis on moving the limited number of promising phase II trials forward as placebo controlled randomized trials, the gold standard for prevention studies. How does one define a placebo for a food? What is the regulatory context of such a food based product? How can such products be produced and standardized to the benefit of a larger, individual trial, and importantly, the research community at large? What are the challenges and opportunities of conducting such trials in the international setting? Finally, how does one make the science practical? PMID- 22307564 TI - A review of cancer in U.S. Hispanic populations. AB - There are compelling reasons to conduct studies of cancer in Hispanics, the fastest growing major demographic group in the United States (from 15% to 30% of the U.S. population by 2050). The genetically admixed Hispanic population coupled with secular trends in environmental exposures and lifestyle/behavioral practices that are associated with immigration and acculturation offer opportunities for elucidating the effects of genetics, environment, and lifestyle on cancer risk and identifying novel risk factors. For example, traditional breast cancer risk factors explain less of the breast cancer risk in Hispanics than in non-Hispanic whites (NHW), and there is a substantially greater proportion of never-smokers with lung cancer in Hispanics than in NHW. Hispanics have higher incidence rates for cancers of the cervix, stomach, liver, and gall bladder than NHW. With respect to these cancers, there are intriguing patterns that warrant study (e.g., depending on country of origin, the five-fold difference in gastric cancer rates for Hispanic men but not Hispanic women). Also, despite a substantially higher incidence rate and increasing secular trend for liver cancer in Hispanics, there have been no studies of Hispanics reported to date. We review the literature and discuss study design options and features that should be considered in future studies. PMID- 22307566 TI - Soy isoflavone supplementation for breast cancer risk reduction: a randomized phase II trial. AB - Soy isoflavone consumption may protect against breast cancer development. We conducted a phase IIB trial of soy isoflavone supplementation to examine its effect on breast epithelial proliferation and other biomarkers in the healthy high-risk breast. One hundred and twenty-six consented women underwent a random fine-needle aspiration (rFNA); those with 4,000 or more epithelial cells were randomized to a double-blind 6-month intervention of mixed soy isoflavones (PTIG 2535) or placebo, followed by repeat rFNA. Cells were examined for Ki-67 labeling index and atypia. Expression of 28 genes related to proliferation, apoptosis, and estrogenic effect was measured using quantitative reverse transcriptase PCR. Hormone and protein levels were measured in nipple aspirate fluid (NAF). All statistical tests were two-sided. Ninety-eight women were evaluable for Ki-67 labeling index. In 49 treated women, the median Ki-67 labeling index was 1.18 at entry and 1.12 post intervention, whereas in 49 placebo subjects, it was 0.97 and 0.92 (P for between-group change: 0.32). Menopausal stratification yielded similar results between groups, but within premenopausal soy-treated women, Ki-67 labeling index increased from 1.71 to 2.18 (P = 0.04). We saw no treatment effect on cytologic atypia or NAF parameters. There were significant increases in the expression of 14 of 28 genes within the soy, but not the control group, without significant between-group differences. Plasma genistein values showed excellent compliance. A 6-month intervention of mixed soy isoflavones in healthy, high-risk adult Western women did not reduce breast epithelial proliferation, suggesting a lack of efficacy for breast cancer prevention and a possible adverse effect in premenopausal women. PMID- 22307567 TI - Accelerated evolution and coevolution drove the evolutionary history of AGPase sub-units during angiosperm radiation. AB - BACKGROUND AND AIMS: ADP-glucose pyrophosphorylase (AGPase) is a key enzyme of starch biosynthesis. In the green plant lineage, it is composed of two large (LSU) and two small (SSU) sub-units encoded by paralogous genes, as a consequence of several rounds of duplication. First, our aim was to detect specific patterns of molecular evolution following duplication events and the divergence between monocotyledons and dicotyledons. Secondly, we investigated coevolution between amino acids both within and between sub-units. METHODS: A phylogeny of each AGPase sub-unit was built using all gymnosperm and angiosperm sequences available in databases. Accelerated evolution along specific branches was tested using the ratio of the non-synonymous to the synonymous substitution rate. Coevolution between amino acids was investigated taking into account compensatory changes between co-substitutions. KEY RESULTS: We showed that SSU paralogues evolved under high functional constraints during angiosperm radiation, with a significant level of coevolution between amino acids that participate in SSU major functions. In contrast, in the LSU paralogues, we identified residues under positive selection (1) following the first LSU duplication that gave rise to two paralogues mainly expressed in angiosperm source and sink tissues, respectively; and (2) following the emergence of grass-specific paralogues expressed in the endosperm. Finally, we found coevolution between residues that belong to the interaction domains of both sub-units. CONCLUSIONS: Our results support the view that coevolution among amino acid residues, especially those lying in the interaction domain of each sub-unit, played an important role in AGPase evolution. First, within SSU, coevolution allowed compensating mutations in a highly constrained context. Secondly, the LSU paralogues probably acquired tissue specific expression and regulatory properties via the coevolution between sub unit interacting domains. Finally, the pattern we observed during LSU evolution is consistent with repeated sub-functionalization under 'Escape from Adaptive Conflict', a model rarely illustrated in the literature. PMID- 22307568 TI - Virus-induced gene silencing (VIGS) in Cysticapnos vesicaria, a zygomorphic flowered Papaveraceae (Ranunculales, basal eudicots). AB - BACKGROUND AND AIMS: Studies of evolutionary diversification in the basal eudicot family Papaveraceae, such as the transition from actinomorphy to zygomorphy, are hampered by the lack of comparative functional studies. So far, gene silencing methods are only available in the actinomorphic species Eschscholzia californica and Papaver somniferum. This study addresses the amenability of Cysticapnos vesicaria, a derived fumitory with zygomorphic flowers, to virus-induced gene silencing (VIGS), and describes vegetative and reproductive traits in this species. METHODS: VIGS-mediated downregulation of the C. vesicaria PHYTOENE DESATURASE gene (CvPDS) and of the FLORICAULA gene CvFLO was carried out using Agrobacterium tumefaciens transfer of Tobacco rattle virus (TRV)-based vectors. Wild-type and vector-treated plants were characterized using reverse transcription-PCR (RT-PCR), in situ hybridization, and macroscopic and scanning electron microscopic imaging. KEY RESULTS: Cysticapnos vesicaria germinates rapidly, can be grown at high density, has a short life cycle and is self compatible. Inoculation of C. vesicaria with a CvPDS-VIGS vector resulted in strong photobleaching of green parts and reduction of endogenous CvPDS transcript levels. Gene silencing persisted during inflorescence development until fruit set. Inoculation of plants with CvFLO-VIGS affected floral phyllotaxis, symmetry and floral organ identities. CONCLUSIONS: The high penetrance, severity and stability of pTRV-mediated silencing, including the induction of meristem-related phenotypes, make C. vesicaria a very promising new focus species for evolutionary developmental (evo-devo) studies in the Papaveraceae. This now enables comparative studies of flower symmetry, inflorescence determinacy and other traits that diversified in the Papaveraceae. PMID- 22307569 TI - Spatiotemporal variation of leaf epidermal cell growth: a quantitative analysis of Arabidopsis thaliana wild-type and triple cyclinD3 mutant plants. AB - BACKGROUND AND AIMS: The epidermis of an expanding dicot leaf is a mosaic of cells differing in identity, size and differentiation stage. Here hypotheses are tested that in such a cell mosaic growth is heterogeneous and changes with time, and that this heterogeneity is not dependent on the cell cycle regulation per se. METHODS: Shape, size and growth of individual cells were followed with the aid of sequential replicas in expanding leaves of wild-type Arabidopsis thaliana and triple cyclinD3 mutant plants, and combined with ploidy estimation using epi fluorescence microscopy. KEY RESULTS: Relative growth rates in area of individual epidermal cells or small cell groups differ several fold from those of adjacent cells, and change in time. This spatial and temporal variation is not related to the size of either the cell or the nucleus. Shape changes and growth within an individual cell are also heterogeneous: anticlinal wall waviness appears at different times in different wall portions; portions of the cell periphery in contact with different neighbours grow with different rates. This variation is not related to cell growth anisotropy. The heterogeneity is typical for both the wild type and cycD3. CONCLUSIONS: Growth of leaf epidermis exhibits spatiotemporal variability. PMID- 22307570 TI - Nutrition for critically ill patients: how much is enough? PMID- 22307572 TI - Secular trends in sex hormones and fractures in men and women. AB - OBJECTIVE: To study secular trends in sex hormones, anthropometry, bone measures and fractures. DESIGN: A random population sample was studied twice and subjects of similar age group were compared 13 years apart. METHODS: X-ray-verified fractures were retrieved from a random population sample of 2400 men and women (participants 1616=67%) aged 25-64 years from the WHO, MONICA Project in Gothenburg, Sweden, in 1995 and 2008. Fasting serum hormones and calcaneal ultrasound were measured in every fourth subject. In fertile women, measurements were performed on cycle day interval 7-9. RESULTS: In 2008, men had lower serum free testosterone than men of similar age in 1995 (P<0.001). Body composition, physical activity and fracture incidence were similar. In women, hormone replacement therapy (HRT) was lower in 2008, 7 vs 28% (P<0.0001), as was serum oestradiol, although use of tranquilisers and leisure time physical activity were higher. In 2008, the fracture incidence was higher in postmenopausal women, 29 vs 17% (P<0.001), and vertebral crush had increased from 8 to 19% of all fractures (P=0.031). Serum cholesterol and triglycerides were lower in all subjects in 2008 compared with that in 1995. CONCLUSIONS: Secular trends were observed with lower serum testosterone in men in 2008, but no effect was seen on the fracture incidence of these fairly young men. In postmenopausal women in 2008, there was a higher fracture incidence along with more vertebral compressions. Lower HRT use, lower serum oestradiol and higher fall risk exposure due with more tranquilisers and leisure time physical activity in 2008 may explain the results. PMID- 22307573 TI - The -258A/G (SNP rs12885300) polymorphism of the human type 2 deiodinase gene is associated with a shift in the pattern of secretion of thyroid hormones following a TRH-induced acute rise in TSH. AB - OBJECTIVE: Type 2 deiodinase gene (DIO2) polymorphisms have been associated with changes in pituitary-thyroid axis homeostasis. The -258A/G (SNP rs12885300) polymorphism has been associated with increased enzymatic activity, but data are conflicting. To characterize the effects of -258A/G polymorphism on intrathyroidal thyroxine (T(4)) to triiodothyronine (T(3)) conversion and thyroid hormone (TH) secretion pattern, we studied the effects of acute, TRH-mediated, TSH stimulation of the thyroid gland. DESIGN: Retrospective analysis. METHODS: The TH secretion in response to 500 MUg i.v. TRH injection was studied in 45 healthy volunteers. RESULTS: Twenty-six subjects (16 females and ten males, 32.8 +/- 10.4 years) were homozygous for the ancestral (-258A/A) allele and 19 (11 females and eight males, 31.1 +/- 10.9 years) were carriers of the (-258G/x) variant. While no differences in the peak TSH and T(3) levels were observed, carriers of the -258G/x allele showed a blunted rise in free T(4) (FT(4); P<0.01). The -258G/x92Thr/Thr haplotype, compared with the other groups, had lower TSH values at 60 min (P<0.03). No differences were observed between genotypes in baseline TH levels. CONCLUSIONS: The -258G/x DIO2 polymorphism variant is associated with a decreased rate of acute TSH-stimulated FT(4) secretion with a normal T(3) release from the thyroid gland consistent with a shift in the reaction equilibrium toward the product. These data indicate that the -258G DIO2 polymorphism causes changes in the pattern of hormone secretion. These findings are a proof of concept that common polymorphisms in DIO2 can subtly affect the circulating levels of TH and might modulate the TH homeostasis. PMID- 22307574 TI - Coping and quality of life after total laryngectomy. AB - OBJECTIVE: To investigate how ways of coping and traditional factors (age, sex, time postlaryngectomy, stage of disease, radiation, alaryngeal speech method) predict global quality of life, head and neck cancer-specific quality of life, and voice-related quality-of-life outcomes after total laryngectomy. STUDY DESIGN: Cross-sectional survey. SETTING: University-based laboratory and speech clinic. SUBJECTS AND METHODS: Sixty-seven individuals who underwent total laryngectomy secondary to cancer were recruited from support groups and professional contacts. Individuals were at minimum 9 months postlaryngectomy. All outcomes were patient reported and included demographic data as well as a number of validated questionnaires: the Ways of Coping-Cancer Version (WOC-CV) scale, the Voice-Related Quality of Life (V-RQOL) scale, and the University of Washington Quality of Life (UW-QOL) composite and global QOL scores. RESULTS: Fifty-three individuals identified a stressful aspect of their laryngectomy. As a set, traditional variables (age, time postlaryngectomy, alaryngeal speech method) accounted for only 5% of global QOL scores but between 25% and 30% of the variance of composite UW-QOL and V-RQOL scores. Time postlaryngectomy was the strongest traditional predictor. Ways of coping accounted for 23% to 32% of all QOL scores. Avoidant coping strategies (both cognitive and behavioral escape) were among the strongest predictors of poorer QOL. When traditional variables were combined with ways of coping, they together accounted for 26% to 46% of the variance of QOL outcomes. CONCLUSION: Coping is important to consider when evaluating postlaryngectomy outcomes, above and beyond traditionally investigated factors. PMID- 22307575 TI - Hypoglossal nerve stimulation and airway changes under fluoroscopy. AB - OBJECTIVE: To characterize the changes in the anteroposterior dimensions of both the retropalatal and retrolingual airway spaces of the pharynx and hyoid bone position during hypoglossal nerve stimulation under general anesthesia in subjects with obstructive sleep apnea. STUDY DESIGN: Cross-sectional. SETTING: Academic center. SUBJECTS AND METHODS: Cross-table fluoroscopic images obtained during hypoglossal nerve stimulation were studied in 26 subjects enrolled in the Apnex Medical Hypoglossal Nerve Stimulation (HGNS) system feasibility trials. Changes in the anteroposterior dimensions (2-dimensional) of the retropalatal and retrolingual airway spaces and hyoid bone position were recorded. Measurements were estimated in millimeters and standardized to each subject's C3 vertebral height. Opening of the pharyngeal airspace was examined relative to body mass index. RESULTS: During hypoglossal nerve stimulation, all subjects demonstrated anterior displacement of the tongue base on fluoroscopy. The average retrolingual airway opening was 0.71 +/- 0.23 C3 vertebral body heights (9 +/- 3 mm). Opening of the retropalatal airway with stimulation occurred in 65% (15/23) of subjects. When present, the average opening was 0.42 +/- 0.14 vertebral heights (5 +/- 3 mm). Anterior displacement of the hyoid occurred in 92% (23/25) of subjects. Retrolingual airway opening was independent of baseline body mass index. CONCLUSION: Unilateral hypoglossal nerve stimulation results in anterior tongue base displacement and an increase in the anterior-posterior retrolingual airway dimensions of the pharynx, independent of body mass index. Opening of the retropalatal airway occurred in a majority of subjects and had a trend toward correlation with body mass index. PMID- 22307571 TI - Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. AB - CONTEXT: The amount of enteral nutrition patients with acute lung injury need is unknown. OBJECTIVE: To determine if initial lower-volume trophic enteral feeding would increase ventilator-free days and decrease gastrointestinal intolerances compared with initial full enteral feeding. DESIGN, SETTING, AND PARTICIPANTS: The EDEN study, a randomized, open-label, multicenter trial conducted from January 2, 2008, through April 12, 2011. Participants were 1000 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. INTERVENTIONS: Participants were randomized to receive either trophic or full enteral feeding for the first 6 days. After day 6, the care of all patients who were still receiving mechanical ventilation was managed according to the full feeding protocol. MAIN OUTCOME MEASURES: Ventilator-free days to study day 28. RESULTS: Baseline characteristics were similar between the trophic-feeding (n = 508) and full-feeding (n = 492) groups. The full-feeding group received more enteral calories for the first 6 days, about 1300 kcal/d compared with 400 kcal/d (P < .001). Initial trophic feeding did not increase the number of ventilator-free days (14.9 [95% CI, 13.9 to 15.8] vs 15.0 [95% CI, 14.1 to 15.9]; difference, 0.1 [95% CI, -1.4 to 1.2]; P = .89) or reduce 60-day mortality (23.2% [95% CI, 19.6% to 26.9%] vs 22.2% [95% CI, 18.5% to 25.8%]; difference, 1.0% [95% CI, 4.1% to 6.3%]; P = .77) compared with full feeding. There were no differences in infectious complications between the groups. Despite receiving more prokinetic agents, the full-feeding group experienced more vomiting (2.2% vs 1.7% of patient feeding days; P = .05), elevated gastric residual volumes (4.9% vs 2.2% of feeding days; P < .001), and constipation (3.1% vs 2.1% of feeding days; P = .003). Mean plasma glucose values and average hourly insulin administration were both higher in the full-feeding group over the first 6 days. CONCLUSION: In patients with acute lung injury, compared with full enteral feeding, a strategy of initial trophic enteral feeding for up to 6 days did not improve ventilator free days, 60-day mortality, or infectious complications but was associated with less gastrointestinal intolerance. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT00609180 and NCT00883948. PMID- 22307576 TI - Can the pathology of a thyroid nodule be determined by positron emission tomography uptake? AB - OBJECTIVES: To determine if standardized uptake values (SUV) on positron emission tomography (PET) are predictive of thyroid pathology and the significance of serial SUV measurements of thyroid nodules over time. STUDY DESIGN: Case series with chart review. SETTING: Academic health center. SUBJECTS: In total, 23,384 PET and PET/computed tomography (CT) scans were performed between December 2001 and April 2011. METHODS: Patients with incidental thyroid uptake were identified. SUV(max), age, sex, size of thyroid lesion, indication for PET scan, and cytology/pathology were collected. RESULTS: Incidental thyroid uptake was noted in 1309 PET scans (5.60%), focal uptake in 690 (2.95%), and diffuse uptake in 619 (2.65%). Complete data were available for 359 PET scans from 103 patients. Malignancy was identified in 28 patients (27%). Twenty-five of the 28 lesions (89%) were primary thyroid malignancies. A significant difference between malignant SUV(max) and benign SUV(max) was found (mean +/- SD, 7.04 +/- 7.88 for malignancies vs 3.85 +/- 3.06 for benign tumors, P = .0292). Receiver operating characteristics curves were constructed on patients with PET data within 3 months of diagnosis and indicated that a SUV(max) of 4.2 differentiated maximally between benign and malignant lesions. Serial SUV uptake had no significant change over time. CONCLUSION: All thyroid nodules with focal uptake on (18)F fluorodeoxyglucose-PET/CT should be considered at higher risk of malignancy than those discovered incidentally by other imaging modalities. Higher SUV(max) values are more indicative of malignant lesions. All lesions should be evaluated with ultrasonography +/- fine-needle aspiration if no clinical contraindications exist. Size of the primary nodule does not influence SUV(max) uptake. PMID- 22307577 TI - Esophageal reflux disease proton pump inhibitor therapy impact on sleep disturbance: a systematic review. AB - OBJECTIVE: To perform a systematic literature review that evaluates the impact of proton pump inhibitor treatment of gastroesophageal reflux disease on sleep disturbance-related outcomes. DATA SOURCES: PubMed, Web of Science, and Cochrane databases were searched from 1989 (when omeprazole became available) to present; additional references gleaned from citations. REVIEW METHODS: The search strategy identified all randomized placebo-controlled clinical trials published in English; both proton pump inhibitor use and outcome measures of sleep disturbance were reported for esophageal reflux disease patients. Using a preestablished systematic review protocol and data extraction format, 4 coauthors independently reviewed all articles. RESULTS: The original search identified 20 articles; 9 were not directly relevant, and 3 were not placebo controlled. Sample sizes varied from 15 to 642; mean age was 47.4 +/- 4.56 years; mean body mass index was 29.4 +/- 2.9; the proportion of women varied widely across studies. Esomeprazole was studied most frequently. More than 50% of publications permitted rescue antacids. Two studies reported polysomnography outcomes, without statistically significant improvement. All studies reported non-polysomnography outcomes; 7 identified statistically significant improvements demonstrating drug treatment superiority over placebo. CONCLUSION: The existing evidence supports the use of proton pump inhibitors as a treatment for esophageal reflux disease to improve quality-of-life sleep disturbance-related outcomes. Given the wide variability in proton pump inhibitor treatments and sleep disturbance-related outcomes reported, however, study-specific results cannot be directly compared or aggregated. This conclusion appears robust not only for 7 of 8 studies included but also for the 3 highest quality studies. PMID- 22307578 TI - Switching between ring closed and open N-incorporated heterocycles with tuneable charges and modular reactivity based upon 5-(2-bromoethyl)phenanthridinium bromide. AB - 5-(2-bromoethyl)phenanthridinium bromide (BEP) undergoes a 3-step-one-pot cyclisation reaction with primary amines allowing the facile synthesis of a vast library of heterocycles. A diverse range of primary aryl amines were explored as reactants to gain insight into the product isolated as a result of the steric and electronic effects of the aryl precursors. Analysis and reaction monitoring with UV-vis and NMR spectroscopy revealed that excessively electron withdrawing groups and sterically hindered amines do not allow for isolation of the common neutral tetrahydroimidazophenanthridine (TIP) structure but allow either the isolation of the charged dihydroimadazophenanthridinium (DIP) or aminoethylphenanthridinium (AEP) products. PMID- 22307579 TI - Illness perceptions in cancer survivors: what is the role of information provision? AB - BACKGROUND: The aim of this study was to provide insight into the relationship between information provision and illness perceptions among cancer survivors. METHODS: All individuals diagnosed with lymphoma, multiple myeloma, endometrial or colorectal cancer between 1998 and 2008, as registered in the Eindhoven Cancer Registry, were eligible for participation. In total, 4446 survivors received a questionnaire including the EORTC-QLQ-INFO25 and the Brief Illness Perception Questionnaire; 69% responded (n = 3080). RESULTS: Lymphoma and multiple myeloma patients were most satisfied with the information they received, and they perceived to having received more information about their treatment and other services (after care) compared with colorectal and endometrial cancer survivors (p < 0.05). Multiple myeloma patients reported the highest scores (conceptualized their illness as very serious) on the illness perception scales. The perceived receipt of more disease-specific information was associated with more personal and treatment control and a better understanding of the illness, whereas the perceived receipt of more information about other services was associated with more negative consequences of the illness on the patients' life, longer perceived duration of illness, less treatment control, more symptoms attributable to the illness, less understanding of, and stronger emotional reaction to the illness (p < 0.05). Satisfaction with the received information was associated with better illness perception on all subscales, except for personal control (p < 0.05). CONCLUSION: Improving the patients' illness perceptions by tailoring the information provision to the needs of patients may help patients to get a more coherent understanding of their illness and will possibly lead to a better health related quality of life. PMID- 22307580 TI - Solid-state and solution structure of a hypervalent AX5 compound: Sb(C6F5)5. AB - Eliminating restraints: a trigonal-bipyramidal structure has been found to be the energetically favored geometry of the hypervalent AX(5) molecule Sb(C(6)F(5))(5) in the solid state and also in fluid solution, where molecules move freely and no crystal packing effects operate. PMID- 22307581 TI - Should bedside sonography be used first to diagnose pneumothorax secondary to blunt trauma? AB - BACKGROUND.: Our purpose was to evaluate the effectiveness of bedside sonography (US) in the detection of pneumothorax secondary to blunt thoracic trauma. METHODS.: In this prospective study, 240 hemithoraces of 120 consecutive patients with multiple trauma were evaluated with chest radiographs (CXR) and bedside thoracic US for the diagnosis of pneumothorax. CT examinations were performed in 68 patients. Fifty-two patients who did not undergo CT examinations were excluded from the study. US examinations were performed independently at bedside by two radiologists who were not informed about CXR and CT findings. CXRs were interpreted by two radiologists who were unaware of the US and CT results. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CXR and US were calculated. RESULTS.: One hundred thirty-six hemithoraces were assessed in 68 patients. A total of 35 pneumothoraces were detected in 33 patients. On US, the diagnosis of pneumothorax was correct in 32 hemithoraces. In 98 hemithoraces without pneumothorax, US was normal. With US examination, there were three false-positive and three false-negative results. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of US were 91.4%, 97%, 91.4%, 97%, and 97%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CXR were 82.7%, 89.7%, 68.5%, 95%, and 89.5%, respectively. CONCLUSIONS.: Bedside thoracic US is an accurate method that can be used in trauma patients instead of CXR for the detection of pneumothorax. PMID- 22307582 TI - Temperature and pressure dependence of the rate coefficient for the reaction between ClO and CH3O2 in the gas-phase. AB - A temperature and pressure kinetic study for the CH(3)O(2) + ClO reaction has been performed using the turbulent flow technique with a chemical ionisation mass spectrometry detection system. An Arrhenius expression was obtained for the overall rate coefficient of CH(3)O(2) + ClO reaction: k(10)(T) = (1.96( 0.24)(+0.28)) * 10(-11) exp[(-626 +/- 35)/T] cm(3) molecule(-1) s(-1) where the uncertainty associated with the rate coefficient is given at the one standard deviation level. Over a range of pressure (100-200 Torr) and temperature (298-223 K) no pressure dependence is observed. The smaller rate coefficients measured at lower temperatures compared with both previous low temperature studies are believed to arise through the reduction of secondary chemistry and greater sensitivity in terms of reactant detection (hence much lower initial concentrations were employed). These new data reduce the effectiveness of ozone loss cycles involving reaction of CH(3)O(2) + ClO in the polar stratosphere by around a factor of 1.5 and restrict the importance of the reaction to the tropical and extra-tropical clean marine environments in the troposphere. PMID- 22307583 TI - Photochemistry of acetylacetone isolated in parahydrogen matrices upon 266 nm irradiation. AB - The photochemistry of the chelated enol form of acetylacetone (AcAc) was investigated by UV excitation of the S(2) state at 266 nm in parahydrogen matrices, complemented by experiments in neon and normal hydrogen matrices. Infrared (IR) spectroscopy, combined with theoretical calculations, was used to identify the photoproducts. Isomerization towards various non-chelated forms (no intramolecular H-bond) of AcAc is the dominant channel whereas fragmentation is very minor. The isomerization kinetics is monitored by IR spectroscopy. Among the seven non-chelated conformers of AcAc, only three are formed in parahydrogen matrices, whereas four are observed in normal hydrogen matrices. This difference suggests that an active tunnelling process between conformers occurs in parahydrogen but is quenched in normal hydrogen where guest-host interactions are stronger. Fragmentation and isomerization of excited AcAc are discussed in the light of these new data. The role of the intermediate triplet state in the S(2)-> S(0) relaxation is confirmed, as the importance of phonons in the condensed phase. PMID- 22307584 TI - CIZ/NMP4 is expressed in B16 melanoma and forms a positive feedback loop with RANKL to promote migration of the melanoma cells. AB - Tumor metastasis to bone is a serious pathological situation that causes severe pain, and deterioration in locomoter function. However, the mechanisms underlying tumor metastasis is still incompletely understood. CIZ/NMP4 is a nucleocytoplasmic shuttling protein and its roles in tumor cells have not been known. We, therefore, hypothesized the role of CIZ/NMP4 in B16 melanoma cells that metastasize to bone. CIZ/NMP4 is expressed in B16 cells. The CIZ/NMP4 expression levels are correlated to the metastatic activity in divergent types of melanoma cells. Overexpression of CIZ/NMP4 increased B16 cell migration in Trans well assay. Conversely, siRNA-based knockdown of CIZ/NMP4 suppressed migratory activity of these cells. As RANKL promotes metastasis of tumor cells in bone, we tested its effect on CIZ in melanoma cells. RANKL treatment enhanced CIZ/NMP4 expression. This increase of CIZ by RANKL promoted migration. Conversely, we identified CIZ/NMP4 binding site in the promoter of RANKL. Furthermore, luciferase assay indicated that CIZ/NMP4 overexpression enhanced RANKL promoter activities, revealing a positive feedback loop of CIZ/NMP4 and RANKL in melanoma. These observations indicate that CIZ/NMP4 is critical regulator of metastasis of melanoma cells. PMID- 22307585 TI - Are biochemical reactions affected by weak magnetic fields? PMID- 22307586 TI - Travels in time: assessing the functional complexity of T cells. PMID- 22307587 TI - QnAs with Harald zur Hausen. PMID- 22307588 TI - Anthony E. Siegman: Laser pioneer, Optical Society president, friend, and colleague. PMID- 22307589 TI - Molecular architecture of the 26S proteasome holocomplex determined by an integrative approach. AB - The 26S proteasome is at the executive end of the ubiquitin-proteasome pathway for the controlled degradation of intracellular proteins. While the structure of its 20S core particle (CP) has been determined by X-ray crystallography, the structure of the 19S regulatory particle (RP), which recruits substrates, unfolds them, and translocates them to the CP for degradation, has remained elusive. Here, we describe the molecular architecture of the 26S holocomplex determined by an integrative approach based on data from cryoelectron microscopy, X-ray crystallography, residue-specific chemical cross-linking, and several proteomics techniques. The "lid" of the RP (consisting of Rpn3/5/6/7/8/9/11/12) is organized in a modular fashion. Rpn3/5/6/7/9/12 form a horseshoe-shaped heterohexamer, which connects to the CP and roofs the AAA-ATPase module, positioning the Rpn8/Rpn11 heterodimer close to its mouth. Rpn2 is rigid, supporting the lid, while Rpn1 is conformationally variable, positioned at the periphery of the ATPase ring. The ubiquitin receptors Rpn10 and Rpn13 are located in the distal part of the RP, indicating that they were recruited to the complex late in its evolution. The modular structure of the 26S proteasome provides insights into the sequence of events prior to the degradation of ubiquitylated substrates. PMID- 22307591 TI - Unidirectionally aligned line patterns driven by entropic effects on faceted surfaces. AB - A simple, versatile approach to the directed self-assembly of block copolymers into a macroscopic array of unidirectionally aligned cylindrical microdomains on reconstructed faceted single crystal surfaces or on flexible, inexpensive polymeric replicas was discovered. High fidelity transfer of the line pattern generated from the microdomains to a master mold is also shown. A single-grained line patterns over arbitrarily large surface areas without the use of top-down techniques is demonstrated, which has an order parameter typically in excess of 0.97 and a slope error of 1.1 deg. This degree of perfection, produced in a short time period, has yet to be achieved by any other methods. The exceptional alignment arises from entropic penalties of chain packing in the facets coupled with the bending modulus of the cylindrical microdomains. This is shown, theoretically, to be the lowest energy state. The atomic crystalline ordering of the substrate is transferred, over multiple length scales, to the block copolymer microdomains, opening avenues to large-scale roll-to-roll type and nanoimprint processing of perfectly patterned surfaces and as templates and scaffolds for magnetic storage media, polarizing devices, and nanowire arrays. PMID- 22307590 TI - Functional profiling of neurons through cellular neuropharmacology. AB - We describe a functional profiling strategy to identify and characterize subtypes of neurons present in a peripheral ganglion, which should be extendable to neurons in the CNS. In this study, dissociated dorsal-root ganglion neurons from mice were exposed to various pharmacological agents (challenge compounds), while at the same time the individual responses of >100 neurons were simultaneously monitored by calcium imaging. Each challenge compound elicited responses in only a subset of dorsal-root ganglion neurons. Two general types of challenge compounds were used: agonists of receptors (ionotropic and metabotropic) that alter cytoplasmic calcium concentration (receptor-agonist challenges) and compounds that affect voltage-gated ion channels (membrane-potential challenges). Notably, among the latter are K-channel antagonists, which elicited unexpectedly diverse types of calcium responses in different cells (i.e., phenotypes). We used various challenge compounds to identify several putative neuronal subtypes on the basis of their shared and/or divergent functional, phenotypic profiles. Our results indicate that multiple receptor-agonist and membrane-potential challenges may be applied to a neuronal population to identify, characterize, and discriminate among neuronal subtypes. This experimental approach can uncover constellations of plasma membrane macromolecules that are functionally coupled to confer a specific phenotypic profile on each neuronal subtype. This experimental platform has the potential to bridge a gap between systems and molecular neuroscience with a cellular-focused neuropharmacology, ultimately leading to the identification and functional characterization of all neuronal subtypes at a given locus in the nervous system. PMID- 22307592 TI - Coaxial multishell nanowires with high-quality electronic interfaces and tunable optical cavities for ultrathin photovoltaics. AB - Silicon nanowires (NWs) could enable low-cost and efficient photovoltaics, though their performance has been limited by nonideal electrical characteristics and an inability to tune absorption properties. We overcome these limitations through controlled synthesis of a series of polymorphic core/multishell NWs with highly crystalline, hexagonally-faceted shells, and well-defined coaxial (p/n) and p/intrinsic/n (p/i/n) diode junctions. Designed 200-300 nm diameter p/i/n NW diodes exhibit ultralow leakage currents of approximately 1 fA, and open-circuit voltages and fill-factors up to 0.5 V and 73%, respectively, under one-sun illumination. Single-NW wavelength-dependent photocurrent measurements reveal size-tunable optical resonances, external quantum efficiencies greater than unity, and current densities double those for silicon films of comparable thickness. In addition, finite-difference-time-domain simulations for the measured NW structures agree quantitatively with the photocurrent measurements, and demonstrate that the optical resonances are due to Fabry-Perot and whispering gallery cavity modes supported in the high-quality faceted nanostructures. Synthetically optimized NW devices achieve current densities of 17 mA/cm(2) and power-conversion efficiencies of 6%. Horizontal integration of multiple NWs demonstrates linear scaling of the absolute photocurrent with number of NWs, as well as retention of the high open-circuit voltages and short-circuit current densities measured for single NW devices. Notably, assembly of 2 NW elements into vertical stacks yields short-circuit current densities of 25 mA/cm(2) with a backside reflector, and simulations further show that such stacking represents an attractive approach for further enhancing performance with projected efficiencies of > 15% for 1.2 MUm thick 5 NW stacks. PMID- 22307593 TI - Constant-speed vibrational signaling along polyethyleneglycol chain up to 60-A distance. AB - A series of azido-PEG-succinimide ester oligomers with a number of repeating PEG units of 0, 4, 8, and 12 (azPEG0, 4, 8, and 12) was investigated using a relaxation-assisted two-dimensional infrared (RA 2DIR) spectroscopy method. The RA 2DIR method relies on the energy transport in molecules and is capable of correlating the frequencies of vibrational modes separated by large through-bond distances. Excitation of the azido group in the compounds at ca. 2,100 cm(-1) generates an excess energy which propagates in the molecule as well as dissipates into the solvent. We discovered that a part of the excess energy propagates ballistically via the covalent backbone of the molecules with a constant speed of ca. 550 m/s. The transport is described as a propagation of a vibrational wavepacket having a mean-free-path length of 10-15 A. The discovery has the potential for developing new efficient signal transduction strategies for molecular electronics and biochemistry. It also permits extending the distances accessible in RA 2DIR structural measurements up to ca. 60 A. PMID- 22307594 TI - Dissociable neural representations of reinforcement and belief prediction errors underlie strategic learning. AB - Decision-making in the presence of other competitive intelligent agents is fundamental for social and economic behavior. Such decisions require agents to behave strategically, where in addition to learning about the rewards and punishments available in the environment, they also need to anticipate and respond to actions of others competing for the same rewards. However, whereas we know much about strategic learning at both theoretical and behavioral levels, we know relatively little about the underlying neural mechanisms. Here, we show using a multi-strategy competitive learning paradigm that strategic choices can be characterized by extending the reinforcement learning (RL) framework to incorporate agents' beliefs about the actions of their opponents. Furthermore, using this characterization to generate putative internal values, we used model based functional magnetic resonance imaging to investigate neural computations underlying strategic learning. We found that the distinct notions of prediction errors derived from our computational model are processed in a partially overlapping but distinct set of brain regions. Specifically, we found that the RL prediction error was correlated with activity in the ventral striatum. In contrast, activity in the ventral striatum, as well as the rostral anterior cingulate (rACC), was correlated with a previously uncharacterized belief-based prediction error. Furthermore, activity in rACC reflected individual differences in degree of engagement in belief learning. These results suggest a model of strategic behavior where learning arises from interaction of dissociable reinforcement and belief-based inputs. PMID- 22307595 TI - Commodity durability, trader specialization, and market performance. AB - The original double auction studies of supply and demand markets established their strong efficiency and equilibrium convergence behavior using economically unsophisticated and untrained subjects. The results were unexpected because all individual costs and values were private and dependent entirely on the market trading process to aggregate the dispersed information into socially desirable outcomes. The exchange environment, however, corresponded to that of perishable, and not re-traded goods in which participants were specialized as buyers or sellers. We report experiments in repeated single-period markets where tradability, and buyer-seller role specialization, is varied by imposing or relaxing a restriction on re-trade within each period. In re-trade markets scope is given to speculative motives unavailable where goods perish on purchase. We observe greatly increased trade volume and decreased efficiency but subject experience increases efficiency. Observed speculation slows convergence by impeding the process whereby individuals learn from the market whether their private circumstances lead them to specialize as buyers or sellers. PMID- 22307596 TI - Infants deploy selective attention to the mouth of a talking face when learning speech. AB - The mechanisms underlying the acquisition of speech-production ability in human infancy are not well understood. We tracked 4-12-mo-old English-learning infants' and adults' eye gaze while they watched and listened to a female reciting a monologue either in their native (English) or nonnative (Spanish) language. We found that infants shifted their attention from the eyes to the mouth between 4 and 8 mo of age regardless of language and then began a shift back to the eyes at 12 mo in response to native but not nonnative speech. We posit that the first shift enables infants to gain access to redundant audiovisual speech cues that enable them to learn their native speech forms and that the second shift reflects growing native-language expertise that frees them to shift attention to the eyes to gain access to social cues. On this account, 12-mo-old infants do not shift attention to the eyes when exposed to nonnative speech because increasing native language expertise and perceptual narrowing make it more difficult to process nonnative speech and require them to continue to access redundant audiovisual cues. Overall, the current findings demonstrate that the development of speech production capacity relies on changes in selective audiovisual attention and that this depends critically on early experience. PMID- 22307597 TI - Efficient coupling of ATP hydrolysis to translocation by RecQ helicase. AB - Helicases are ubiquitous enzymes that unwind double-stranded DNA (dsDNA) to reveal single-stranded DNA (ssDNA) during essential processes such as replication, transcription, or repair. The Escherichia coli RecQ protein is a 3' to 5' helicase, which functions in the processes of homologous recombination and replication fork restart. Here, we analyzed the relationship between ATP hydrolysis by RecQ and its translocation on ssDNA. We monitored a single round of RecQ translocation on ssDNA by measuring the rates of inorganic phosphate release during translocation, and the dissociation of RecQ from ssDNA. We find that RecQ translocates with a rate of 16( +/- 4) nucleotides/s and moves on average only 36( +/- 2) nucleotides before dissociating. Fitting to an n-step kinetic model suggests that the helicase displays a nonuniform translocation mechanism in which it moves approximately five nucleotides rapidly before undergoing a rate-limiting kinetic slow step. Unexpectedly, RecQ requires a length of 34( +/- 3) nucleotides to bind and translocate on ssDNA. This large site size suggests that several monomers are required to bind DNA prior to translocation. Energetically, the RecQ helicase couples the hydrolysis of one ATP molecule to the translocation of more than one nucleotide (1.6 +/- 0.3). Thus, our data show that RecQ translocates on ssDNA by efficiently coupling the hydrolysis of one ATP molecule into structural alterations that result in movement of approximately two nucleotides, presumably by an inchworm mechanism. These attributes are consistent with the function of RecQ in recombination and replication. PMID- 22307598 TI - Critical role of a transmembrane lysine in aminophospholipid transport by mammalian photoreceptor P4-ATPase ATP8A2. AB - ATP8A2 is a P(4)-ATPase ("flippase") located in membranes of retinal photoreceptors, brain cells, and testis, where it mediates transport of aminophospholipids toward the cytoplasmic leaflet. It has long been an enigma whether the mechanism of P(4)-ATPases resembles that of the well-characterized cation-transporting P-type ATPases, and it is unknown whether the flippases interact directly with the lipid and with counterions. Our results demonstrate that ATP8A2 forms a phosphoenzyme intermediate at the conserved aspartate (Asp(416)) in the P-type ATPase signature sequence and exists in E(1)P and E(2)P forms similar to the archetypical P-type ATPases. Using the properties of the phosphoenzyme, the partial reaction steps of the transport cycle were examined, and the roles of conserved residues Asp(196), Glu(198), Lys(873), and Asn(874) in the transport mechanism were elucidated. The former two residues in the A-domain T/D-G-E-S/T motif are involved in catalysis of E(2)P dephosphorylation, the glutamate being essential. Transported aminophospholipids activate the dephosphorylation similar to K(+) activation of dephosphorylation in Na(+),K(+) ATPase. Lys(873) mutants (particularly K873A and K873E) display a markedly reduced sensitivity to aminophospholipids. Hence, Lys(873), located in transmembrane segment M5 at a "hot spot" for cation binding in Ca(2+)-ATPase and Na(+),K(+)-ATPase, appears to participate directly in aminophospholipid binding or to mediate a crucial interaction within the ATP8A2-CDC50 complex. By contrast, Lys(865) is unimportant for aminophospholipid sensitivity. Binding of Na(+), H(+), K(+), Cl(-), or Ca(2+) to the E(1) form as a counterion is not required for activation of phosphorylation from ATP. Therefore, phospholipids could be the only substrate transported by ATP8A2. PMID- 22307599 TI - Differential regulation of the activity of deleted in liver cancer 1 (DLC1) by tensins controls cell migration and transformation. AB - The epithelial growth factor receptor plays an important role in cell migration and cancer metastasis, but the underlying molecular mechanism is not fully understood. We show here that differential regulation of the Ras-homology-GTPase activating protein [corrected] (Rho-GAP) activity of deleted in liver cancer 1 (DLC1) by tensin3 and COOH-terminal tensin-like protein (cten) controls EGF driven cell migration and transformation. Tensin3 binds DLC1 through its actin binding domain, a region that is missing in cten, and thereby releases an autoinhibitory interaction between the sterile alpha motif and Rho-GAP domains of DLC1. Consequently, tensin3, but not cten, promotes the activation of DLC1, which, in turn, leads to inactivation of RhoA and decreased cell migration. Depletion of endogenous tensin3, but not cten, augmented the formation of actin stress fibers and focal adhesions and enhanced cell motility. These effects were, however, ablated by an inhibitor of the Rho-associated protein kinase. Importantly, activation of DLC1 by tensin3 or its actin-binding domain drastically reduced the anchorage-independent growth of transformed cells. Our study therefore links dynamic regulation of tensin family members by EGF to Rho GAP through DLC1 and suggests that the tensin-DLC1-RhoA signaling axis plays an important role in tumorigenesis and cancer metastasis, and may be explored for cancer intervention. PMID- 22307600 TI - Protein-binding dynamics imaged in a living cell. AB - Historically, rate constants were determined in vitro and it was unknown whether they were valid for in vivo biological processes. Here, we bridge this gap by measuring binding dynamics between a pair of proteins in living HeLa cells. Binding of a beta-lactamase to its protein inhibitor was initiated by microinjection and monitored by Forster resonance energy transfer. Association rate constants for the wild-type and an electrostatically optimized mutant were only 25% and 50% lower than in vitro values, whereas no change in the rate constant was observed for a slower binding mutant. These changes are much smaller than might be anticipated considering the high macromolecular crowding within the cell. Single-cell analyses of association rate constants and fluorescence recovery after photobleaching reveals a naturally occurring variation in cell density, which is translated to an up to a twofold effect on binding rate constants. The data show that for this model protein interaction the intracellular environment had only a small effect on the association kinetics, justifying the extrapolation of in vitro data to processes in the cell. PMID- 22307601 TI - Tracking energy transfer between light harvesting complex 2 and 1 in photosynthetic membranes grown under high and low illumination. AB - Energy transfer (ET) between B850 and B875 molecules in light harvesting complexes LH2 and LH1/RC (reaction center) complexes has been investigated in membranes of Rhodopseudomonas palustris grown under high- and low-light conditions. In these bacteria, illumination intensity during growth strongly affects the type of LH2 complexes synthesized, their optical spectra, and their amount of energetic disorder. We used a specially built femtosecond spectrometer, combining tunable narrowband pump with broadband white-light probe pulses, together with an analytical method based on derivative spectroscopy for disentangling the congested transient absorption spectra of LH1 and LH2 complexes. This procedure allows real-time tracking of the forward (LH2 -> LH1) and backward (LH2<-LH1) ET processes and unambiguous determination of the corresponding rate constants. In low-light grown samples, we measured lower ET rates in both directions with respect to high-light ones, which is explained by reduced spectral overlap between B850 and B875 due to partial redistribution of oscillator strength into a higher energetic exciton transition. We find that the low-light adaptation in R. palustris leads to a reduced elementary backward ET rate, in accordance with the low probability of two simultaneous excitations reaching the same LH1/RC complex under weak illumination. Our study suggests that backward ET is not just an inevitable consequence of vectorial ET with small energetic offsets, but is in fact actively managed by photosynthetic bacteria. PMID- 22307602 TI - beta-Bulge triggers route-switching on the functional landscape of interleukin 1beta. AB - Proteins fold into three-dimensional structures in a funneled energy landscape. This landscape is also used for functional activity. Frustration in this landscape can arise from the competing evolutionary pressures of biological function and reliable folding. Thus, the ensemble of partially folded states can populate multiple routes on this journey to the native state. Although protein folding kinetics experiments have shown the presence of such routes for several proteins, there has been sparse information about the structural diversity of these routes. In addition, why a given protein populates a particular route more often than another protein of similar structure and sequence is not clear. Whereas multiple routes are observed in theoretical studies on the folding of interleukin-1beta (IL-1beta), experimental results indicate one dominant route where the central portion of the protein folds first, and is then followed by closure of the barrel in this beta-trefoil fold. Here we show, using a combination of computation and experiment, that the presence of functionally important regions like the beta-bulge in the signaling protein IL-1beta strongly influences the choice of folding routes. By deleting the beta-bulge, we directly observe the presence of route-switching. This route-switching provides a direct link between route selection and the folding and functional landscapes of a protein. PMID- 22307603 TI - Automated selection of stabilizing mutations in designed and natural proteins. AB - The ability to engineer novel protein folds, conformations, and enzymatic activities offers enormous potential for the development of new protein therapeutics and biocatalysts. However, many de novo and redesigned proteins exhibit poor hydrophobic packing in their predicted structures, leading to instability or insolubility. The general utility of rational, structure-based design would greatly benefit from an improved ability to generate well-packed conformations. Here we present an automated protocol within the RosettaDesign framework that can identify and improve poorly packed protein cores by selecting a series of stabilizing point mutations. We apply our method to previously characterized designed proteins that exhibited a decrease in stability after a full computational redesign. We further demonstrate the ability of our method to improve the thermostability of a well-behaved native protein. In each instance, biophysical characterization reveals that we were able to stabilize the original proteins against chemical and thermal denaturation. We believe our method will be a valuable tool for both improving upon designed proteins and conferring increased stability upon native proteins. PMID- 22307604 TI - Crystal structure of a Tankyrase-Axin complex and its implications for Axin turnover and Tankyrase substrate recruitment. AB - Axin is a tumor suppressor and a key negative regulator of the Wnt/beta-catenin signaling pathway. Axin turnover is controlled by its poly-ADP-ribosylation catalyzed by tankyrase (TNKS), which requires the direct interaction of Axin with TNKS. This interaction is thus an attractive drug target for treating cancers, brain injuries, and other diseases where beta-catenin is involved. Here we report the crystal structure of a mouse TNKS1 fragment containing ankyrin-repeat clusters 2 and 3 (ARC2-3) in a complex with the TNKS-binding domain of mouse Axin1. Surprisingly, we found that Axin contains two discrete TNKS-binding segments, both of which bind simultaneously to the two ARC2 domains in the ARC2-3 homodimer. Our crystal structure shows that in each TNKS-binding segment of Axin there is a conserved glycine residue that lies in the bottom of a narrow "gate" formed by two parallel tyrosine side chains on the TNKS surface. This glycine selection gate is crucial for TNKS-Axin interactions, as mutation of the TNKS gate-forming residues, or mutation of either glycine residue in the two Axin segments, completely abolishes the binding of the corresponding Axin segment to TNKS. The bivalent binding of Axin to TNKS is required for Axin turnover, since mutations in either gate-binding glycine residue in Axin lead to Axin stabilization in the cell. In addition, our analyses also reveal the structural basis for TNKS substrate recruitment, and shed light on the overall structure of TNKS that should help in developing specific inhibitors of Wnt/beta-catenin signaling. PMID- 22307605 TI - Spatial organization of the extracellular matrix regulates cell-cell junction positioning. AB - The organization of cells into epithelium depends on cell interaction with both the extracellular matrix (ECM) and adjacent cells. The role of cell-cell adhesion in the regulation of epithelial topology is well-described. ECM is better known to promote cell migration and provide a structural scaffold for cell anchoring, but its contribution to multicellular morphogenesis is less well-understood. We developed a minimal model system to investigate how ECM affects the spatial organization of intercellular junctions. Fibronectin micropatterns were used to constrain the location of cell-ECM adhesion. We found that ECM affects the degree of stability of intercellular junction positioning and the magnitude of intra- and intercellular forces. Intercellular junctions were permanently displaced, and experienced large perpendicular tensional forces as long as they were positioned close to ECM. They remained stable solely in regions deprived of ECM, where they were submitted to lower tensional forces. The heterogeneity of the spatial organization of ECM induced anisotropic distribution of mechanical constraints in cells, which seemed to adapt their position to minimize both intra- and intercellular forces. These results uncover a morphogenetic role for ECM in the mechanical regulation of cells and intercellular junction positioning. PMID- 22307606 TI - Soluble factors produced by activated CD4+ T cells modulate EBV latency. AB - Following infection with Epstein-Barr virus (EBV), the virus is carried for life in the memory B-cell compartment in a silent state (latency I/0). These cells do not resemble the proliferating lymphoblastoid cells (LCLs) (latency III) that are generated after infection. It is of fundamental significance to identify how the different EBV expression patterns are established in the latently infected cell. In view of the prompt activatability of CD4(+) T cells in primary EBV infection, and their role in B-cell differentiation, we studied the involvement of CD4(+) T cells in the regulation of EBV latency. Lymphoblastoid cell lines (LCLs) were cocultured with autologous or allogeneic CD4(+) T cells. Activated T cells influenced the expression of two key viral proteins that determine the fate of the infected B cell. EBNA2 was down-regulated, whereas LMP1 was unregulated and the cells proliferated less. This was paralleled by the down-regulation of the latency III promoter (Cp). Experiments performed in the transwell system showed that this change does not require cell contact, but it is mediated by soluble factors. Neutralizing experiments proved that the up-regulation of LMP1 is, to some extent, mediated by IL21, but this cytokine was not responsible for EBNA2 down-regulation. This effect was partly mediated by soluble CD40L. We detected similar regulatory functions of T cells in in vitro-infected lymphocyte populations. In conclusion, our results revealed an additional mechanism by which CD4(+) T cells can control the EBV-induced B-cell proliferation. PMID- 22307607 TI - Cytoskeletal protein filamin A is a nucleolar protein that suppresses ribosomal RNA gene transcription. AB - Filamin A (FLNA) is an actin-binding protein with a well-established role in the cytoskeleton, where it determines cell shape and locomotion by cross-linking actin filaments. Mutations in FLNA are associated with a wide range of genetic disorders. Here we demonstrate a unique role for FLNA as a nucleolar protein that associates with the RNA polymerase I (Pol I) transcription machinery to suppress rRNA gene transcription. We show that depletion of FLNA by siRNAs increased rRNA expression, rDNA promoter activity and cell proliferation. Immunodepletion of FLNA from nuclear extracts resulted in a decrease in rDNA promoter-driven transcription in vitro. FLNA coimmunoprecipitated with the Pol I components actin, TIF-IA, and RPA40, and their occupancy of the rDNA promoter was increased in the absence of FLNA in vivo. The FLNA actin-binding domain is essential for the suppression of rRNA expression and for inhibiting recruitment of the Pol I machinery to the rDNA promoter. These findings reveal an additional role for FLNA as a regulator of rRNA gene expression and have important implications for our understanding of the role of FLNA in human disease. PMID- 22307609 TI - Plasma membrane recruitment and activation of the AGC kinase Ypk1 is mediated by target of rapamycin complex 2 (TORC2) and its effector proteins Slm1 and Slm2. AB - The yeast AGC kinase orthologs Ypk1 and Ypk2 control several important cellular processes, including actin polarization, endocytosis, and sphingolipid metabolism. Activation of Ypk1/2 requires phosphorylation by kinases localized at the plasma membrane (PM), including the 3-phosphoinositide-dependent kinase 1 orthologs Pkh1/Pkh2 and the target of rapamycin complex 2 (TORC2). Unlike their mammalian counterparts SGK and Akt, Ypk1 and Ypk2 lack an identifiable lipid targeting motif; therefore, how these proteins are recruited to the PM has remained elusive. To explore Ypk1/2 function, we constructed ATP analog-sensitive alleles of both kinases and monitored global changes in gene expression following their inhibition, where we observed increased expression of stress-responsive target genes controlled by Ca(2+)-dependent phosphatase calcineurin. TORC2 has been shown previously to negatively regulate calcineurin in part by phosphorylating two related proteins, Slm1 and Slm2, which associate with the PM via plextrin homology domains. We therefore investigated the relationship between Slm1 and Ypk1 and discovered that these proteins interact physically and that Slm1 recruits Ypk1 to the PM for phosphorylation by TORC2. We observed further that these steps facilitate subsequent phosphorylation of Ypk1 by Pkh1/2. Remarkably, a requirement for Slm1, can be bypassed by fusing the plextrin homology domain of Slm1 alone onto Ypk1, demonstrating that the essential function of Slm1 is largely attributable to its role in Ypk1 activation. These findings both extend the scope of cellular processes regulated by Ypk1/2 to include negative regulation of calcineurin and broaden the repertoire of mechanisms for membrane recruitment and activation of a protein kinase. PMID- 22307608 TI - Brush border myosin Ia has tumor suppressor activity in the intestine. AB - The loss of the epithelial architecture and cell polarity/differentiation is known to be important during the tumorigenic process. Here we demonstrate that the brush border protein Myosin Ia (MYO1A) is important for polarization and differentiation of colon cancer cells and is frequently inactivated in colorectal tumors by genetic and epigenetic mechanisms. MYO1A frame-shift mutations were observed in 32% (37 of 116) of the colorectal tumors with microsatellite instability analyzed, and evidence of promoter methylation was observed in a significant proportion of colon cancer cell lines and primary colorectal tumors. The loss of polarization/differentiation resulting from MYO1A inactivation is associated with higher tumor growth in soft agar and in a xenograft model. In addition, the progression of genetically and carcinogen-initiated intestinal tumors was significantly accelerated in Myo1a knockout mice compared with Myo1a wild-type animals. Moreover, MYO1A tumor expression was found to be an independent prognostic factor for colorectal cancer patients. Patients with low MYO1A tumor protein levels had significantly shorter disease-free and overall survival compared with patients with high tumoral MYO1A (logrank test P = 0.004 and P = 0.009, respectively). The median time-to-disease recurrence in patients with low MYO1A was 1 y, compared with >9 y in the group of patients with high MYO1A. These results identify MYO1A as a unique tumor-suppressor gene in colorectal cancer and demonstrate that the loss of structural brush border proteins involved in cell polarity are important for tumor development. PMID- 22307610 TI - Nematode sperm maturation triggered by protease involves sperm-secreted serine protease inhibitor (Serpin). AB - Spermiogenesis is a series of poorly understood morphological, physiological and biochemical processes that occur during the transition of immotile spermatids into motile, fertilization-competent spermatozoa. Here, we identified a Serpin (serine protease inhibitor) family protein (As_SRP-1) that is secreted from spermatids during nematode Ascaris suum spermiogenesis (also called sperm activation) and we showed that As_SRP-1 has two major functions. First, As_SRP-1 functions in cis to support major sperm protein (MSP)-based cytoskeletal assembly in the spermatid that releases it, thereby facilitating sperm motility acquisition. Second, As_SRP-1 released from an activated sperm inhibits, in trans, the activation of surrounding spermatids by inhibiting vas deferens derived As_TRY-5, a trypsin-like serine protease necessary for sperm activation. Because vesicular exocytosis is necessary to create fertilization-competent sperm in many animal species, components released during this process might be more important modulators of the physiology and behavior of surrounding sperm than was previously appreciated. PMID- 22307611 TI - Transcription factor WRKY23 assists auxin distribution patterns during Arabidopsis root development through local control on flavonol biosynthesis. AB - Gradients of the plant hormone auxin, which depend on its active intercellular transport, are crucial for the maintenance of root meristematic activity. This directional transport is largely orchestrated by a complex interaction of specific influx and efflux carriers that mediate the auxin flow into and out of cells, respectively. Besides these transport proteins, plant-specific polyphenolic compounds known as flavonols have been shown to act as endogenous regulators of auxin transport. However, only limited information is available on how flavonol synthesis is developmentally regulated. Using reduction-of-function and overexpression approaches in parallel, we demonstrate that the WRKY23 transcription factor is needed for proper root growth and development by stimulating the local biosynthesis of flavonols. The expression of WRKY23 itself is controlled by auxin through the Auxin Response Factor 7 (ARF7) and ARF19 transcriptional response pathway. Our results suggest a model in which WRKY23 is part of a transcriptional feedback loop of auxin on its own transport through local regulation of flavonol biosynthesis. PMID- 22307612 TI - BARHL2 transcription factor regulates the ipsilateral/contralateral subtype divergence in postmitotic dI1 neurons of the developing spinal cord. AB - In the dorsal spinal cord, distinct interneuron classes relay specific somatosensory information, such as touch, heat, and pain, from the periphery to higher brain centers via ipsilateral and contralateral axonal pathways. The transcriptional mechanisms by which dorsal interneurons choose between ipsilateral and contralateral projection fates are unknown. Here, we show that a single transcription factor (TF), BARHL2, regulates this choice in proprioceptive dI1 interneurons by selectively suppressing cardinal dI1contra features in dI1ipsi neurons, despite expression by both subtypes. Strikingly, dI1ipsi neurons in Barhl2-null mice exhibit a dI1contra cell settling pattern in the medial deep dorsal horn, and, most importantly, they project axons contralaterally. These aberrations are preceded by ectopic dI1ipsi expression of the defining dI1contra TF, LHX2, and down-regulation of the dI1ipsi-enriched TF, BARHL1. Taken together, these results elucidate BARHL2 as a critical postmitotic regulator of dI1 subtype diversification, as well as its intermediate position in the dI1 genetic hierarchy. PMID- 22307613 TI - Transcriptional interpretation of the EGF receptor signaling gradient. AB - Epidermal growth factor receptor (EGFR) controls a wide range of developmental events, from body axes specification in insects to cardiac development in humans. During Drosophila oogenesis, a gradient of EGFR activation patterns the follicular epithelium. Multiple transcriptional targets of EGFR in this tissue have been identified, but their regulatory elements are essentially unknown. We report the regulatory elements of broad (br) and pipe (pip), two important targets of EGFR signaling in Drosophila oogenesis. br is expressed in a complex pattern that prefigures the formation of respiratory eggshell appendages. We found that this pattern is generated by dynamic activities of two regulatory elements, which display different responses to Pointed, Capicua, and Mirror, transcription factors involved in the EGFR-mediated gene expression. One of these elements is active in a pattern similar to pip, a gene repressed by EGFR and essential for establishing the dorsoventral polarity of the embryo. We demonstrate that this similarity of expression depends on a common sequence motif that binds Mirror in vitro and is essential for transcriptional repression in vivo. PMID- 22307614 TI - Homeobox gene distal-less is required for neuronal differentiation and neurite outgrowth in the Drosophila olfactory system. AB - Vertebrate Dlx genes have been implicated in the differentiation of multiple neuronal subtypes, including cortical GABAergic interneurons, and mutations in Dlx genes have been linked to clinical conditions such as epilepsy and autism. Here we show that the single Drosophila Dlx homolog, distal-less, is required both to specify chemosensory neurons and to regulate the morphologies of their axons and dendrites. We establish that distal-less is necessary for development of the mushroom body, a brain region that processes olfactory information. These are important examples of distal-less function in an invertebrate nervous system and demonstrate that the Drosophila larval olfactory system is a powerful model in which to understand distal-less functions during neurogenesis. PMID- 22307615 TI - Carnivorous dinocephalian from the Middle Permian of Brazil and tetrapod dispersal in Pangaea. AB - The medial Permian (~270-260 Ma: Guadalupian) was a time of important tetrapod faunal changes, in particular reflecting a turnover from pelycosaurian- to therapsid-grade synapsids. Until now, most knowledge on tetrapod distribution during the medial Permian has come from fossils found in the South African Karoo and the Russian Platform, whereas other areas of Pangaea are still poorly known. We present evidence for the presence of a terrestrial carnivorous vertebrate from the Middle Permian of South America based on a complete skull. Pampaphoneus biccai gen. et sp. nov. was a dinocephalian "mammal-like reptile" member of the Anteosauridae, an early therapsid predator clade known only from the Middle Permian of Russia, Kazakhstan, China, and South Africa. The genus is characterized, among other features, by postorbital bosses, short, bulbous postcanines, and strongly recurved canines. Phylogenetic analysis indicates that the Brazilian dinocephalian occupies a middle position within the Anteosauridae, reinforcing the model of a global distribution for therapsids as early as the Guadalupian. The close phylogenetic relationship of the Brazilian species to dinocephalians from South Africa and the Russian Platform suggests a closer faunistic relationship between South America and eastern Europe than previously thought, lending support to a Pangaea B-type continental reconstruction. PMID- 22307616 TI - Exceptionally preserved crustaceans from western Canada reveal a cryptic Cambrian radiation. AB - The early history of crustaceans is obscured by strong biases in fossil preservation, but a previously overlooked taphonomic mode yields important complementary insights. Here we describe diverse crustacean appendages of Middle and Late Cambrian age from shallow-marine mudstones of the Deadwood Formation in western Canada. The fossils occur as flattened and fragmentary carbonaceous cuticles but provide a suite of phylogenetic and ecological data by virtue of their detailed preservation. In addition to an unprecedented range of complex, largely articulated filtering limbs, we identify at least four distinct types of mandible. Together, these fossils provide the earliest evidence for crown-group branchiopods and total-group copepods and ostracods, extending the respective ranges of these clades back from the Devonian, Pennsylvanian, and Ordovician. Detailed similarities with living forms demonstrate the early origins and subsequent conservation of various complex food-handling adaptations, including a directional mandibular asymmetry that has persisted through half a billion years of evolution. At the same time, the Deadwood fossils indicate profound secular changes in crustacean ecology in terms of body size and environmental distribution. The earliest radiation of crustaceans is largely cryptic in the fossil record, but "small carbonaceous fossils" reveal organisms of surprisingly modern aspect operating in an unfamiliar biosphere. PMID- 22307617 TI - Experimental evolution of multicellularity. AB - Multicellularity was one of the most significant innovations in the history of life, but its initial evolution remains poorly understood. Using experimental evolution, we show that key steps in this transition could have occurred quickly. We subjected the unicellular yeast Saccharomyces cerevisiae to an environment in which we expected multicellularity to be adaptive. We observed the rapid evolution of clustering genotypes that display a novel multicellular life history characterized by reproduction via multicellular propagules, a juvenile phase, and determinate growth. The multicellular clusters are uniclonal, minimizing within cluster genetic conflicts of interest. Simple among-cell division of labor rapidly evolved. Early multicellular strains were composed of physiologically similar cells, but these subsequently evolved higher rates of programmed cell death (apoptosis), an adaptation that increases propagule production. These results show that key aspects of multicellular complexity, a subject of central importance to biology, can readily evolve from unicellular eukaryotes. PMID- 22307618 TI - Evolution of CpG island promoter function underlies changes in KChIP2 potassium channel subunit gene expression in mammalian heart. AB - Scaling of cardiac electrophysiology with body mass requires large changes in the ventricular action potential duration and heart rate in mammals. These changes in cellular electrophysiological function are produced by systematic and coordinated changes in the expression of multiple ion channel and transporter genes. Expression of one important potassium current, the transient outward current (I(to)), changes significantly during mammalian evolution. Changes in I(to) expression are determined, in part, by variation in the expression of an obligatory auxiliary subunit encoded by the KChIP2 gene. The KChIP2 gene is expressed in both cardiac myocytes and neurons and transcription in both cell types is initiated from the same CpG island promoter. Species-dependent variation of KChIP2 expression in heart is mediated by the evolution of the cis-regulatory function of this gene. Surprisingly, the major locus of evolutionary change for KChIP2 gene expression in heart lies within the CpG island core promoter. The results demonstrate that CpG island promoters are not simply permissive for gene expression but can also contribute to tissue-selective expression and, as such, can function as an important locus for the evolution of cis-regulatory function. More generally, evolution of the cis-regulatory function of voltage-gated ion channel genes appears to be an effective and efficient way to modify channel expression levels to optimize electrophysiological function. PMID- 22307619 TI - Complementary costimulation of human T-cell subpopulations by cluster of differentiation 28 (CD28) and CD81. AB - Cluster of differentiation 81 (CD81) is a widely expressed tetraspanin molecule that physically associates with CD4 and CD8 on the surface of human T cells. Coengagement of CD81 and CD3 results in the activation and proliferation of T cells. CD81 also costimulated mouse T cells that lack CD28, suggesting either a redundant or a different mechanism of action. Here we show that CD81 and CD28 have a preference for different subsets of T cells: Primary human naive T cells are better costimulated by CD81, whereas the memory T-cell subsets and Tregs are better costimulated by CD28. The more efficient activation of naive T cells by CD81 was due to prolonged signal transduction compared with that by CD28. We found that IL-6 played a role in the activation of the naive T-cell subset by CD81. Combined costimulation through both CD28 and CD81 resulted in an additive effect on T-cell activation. Thus, these two costimulatory molecules complement each other both in the strength of signal transduction and in T-cell subset inclusions. Costimulation via CD81 might be useful for expansion of T cells for adoptive immunotherapy to allow the inclusion of naive T cells with their broad repertoire. PMID- 22307620 TI - Toll-like receptor 5 (TLR5), IL-1beta secretion, and asparagine endopeptidase are critical factors for alveolar macrophage phagocytosis and bacterial killing. AB - A deficit in early clearance of Pseudomonas aeruginosa (P. aeruginosa) is crucial in nosocomial pneumonia and in chronic lung infections. Few studies have addressed the role of Toll-like receptors (TLRs), which are early pathogen associated molecular pattern receptors, in pathogen uptake and clearance by alveolar macrophages (AMs). Here, we report that TLR5 engagement is crucial for bacterial clearance by AMs in vitro and in vivo because unflagellated P. aeruginosa or different mutants defective in TLR5 activation were resistant to AM phagocytosis and killing. In addition, the clearance of PAK (a wild-type P. aeruginosa strain) by primary AMs was causally associated with increased IL-1beta release, which was dramatically reduced with PAK mutants or in WT PAK-infected primary TLR5(-/-) AMs, demonstrating the dependence of IL-1beta production on TLR5. We showed that this IL-1beta production was important in endosomal pH acidification and in inducing the killing of bacteria by AMs through asparagine endopeptidase (AEP), a key endosomal cysteine protease. In agreement, AMs from IL 1R1(-/-) and AEP(-/-) mice were unable to kill P. aeruginosa. Altogether, these findings demonstrate that TLR5 engagement plays a major role in P. aeruginosa internalization and in triggering IL-1beta formation. PMID- 22307621 TI - Scaffold protein Disc large homolog 1 is required for T-cell receptor-induced activation of regulatory T-cell function. AB - Foxp3(+)CD4(+)CD25(high) regulatory T cell (Treg) suppression of inflammation depends on T-cell receptor-mediated Nuclear Factor of Activated T cells c1 (NFATc1) activation with reduced Akt activity. We investigated the role of the scaffold protein Disc large homolog 1 (Dlgh1) in linking the T-cell receptor to this unique signaling outcome. The Treg immunological synapse (IS) recruited fourfold more Dlgh1 than conventional CD4(+) T-cell IS. Tregs isolated from patients with active rheumatoid arthritis, or treated with tumor necrosis factor alpha, displayed reduced function and diminished Dlgh1 recruitment to the IS. Furthermore, Dlgh1 silencing abrogated Treg function, impaired NFATc1 activation, reduced phosphatase and tensin homolog levels, and increased Akt activation. Dlgh1 operates independently of the negative feedback pathway mediated by the related adapter protein Carma1 and thus presents an array of unique targets to selectively manipulate Treg function. PMID- 22307622 TI - Dickkopf-3, an immune modulator in peripheral CD8 T-cell tolerance. AB - In healthy individuals, T cells react against incoming pathogens, but remain tolerant to self-antigens, thereby preventing autoimmune reactions. CD4 regulatory T cells are major contributors in induction and maintenance of peripheral tolerance, but a regulatory role has been also reported for several subsets of CD8 T cells. To determine the molecular basis of peripheral CD8 T-cell tolerance, we exploited a double transgenic mouse model in which CD8 T cells are neonatally tolerized following interaction with a parenchymal self-antigen. These tolerant CD8 T cells have regulatory capacity and can suppress T cells in an antigen-specific manner during adulthood. Dickkopf-3 (DKK3) was found to be expressed in the tolerant CD8 T cells and to be essential for the observed CD8 T cell tolerance. In vitro, genetic deletion of DKK3 or blocking with antibodies restored CD8 T-cell proliferation and IL-2 production in response to the tolerizing self-antigen. Moreover, exogenous DKK3 reduced CD8 T-cell reactivity. In vivo, abrogation of DKK3 function reversed tolerance, leading to eradication of tumors expressing the target antigen and to rejection of autologous skin grafts. Thus, our findings define DKK3 as a immune modulator with a crucial role for CD8 T-cell tolerance. PMID- 22307623 TI - Cooperative effects of aminopeptidase N (CD13) expressed by nonmalignant and cancer cells within the tumor microenvironment. AB - Processes that promote cancer progression such as angiogenesis require a functional interplay between malignant and nonmalignant cells in the tumor microenvironment. The metalloprotease aminopeptidase N (APN; CD13) is often overexpressed in tumor cells and has been implicated in angiogenesis and cancer progression. Our previous studies of APN-null mice revealed impaired neoangiogenesis in model systems without cancer cells and suggested the hypothesis that APN expressed by nonmalignant cells might promote tumor growth. We tested this hypothesis by comparing the effects of APN deficiency in allografted malignant (tumor) and nonmalignant (host) cells on tumor growth and metastasis in APN-null mice. In two independent tumor graft models, APN activity in both the tumors and the host cells cooperate to promote tumor vascularization and growth. Loss of APN expression by the host and/or the malignant cells also impaired lung metastasis in experimental mouse models. Thus, cooperation in APN expression by both cancer cells and nonmalignant stromal cells within the tumor microenvironment promotes angiogenesis, tumor growth, and metastasis. PMID- 22307624 TI - Oncogene-specific activation of tyrosine kinase networks during prostate cancer progression. AB - Dominant mutations or DNA amplification of tyrosine kinases are rare among the oncogenic alterations implicated in prostate cancer. We demonstrate that castration-resistant prostate cancer (CRPC) in men exhibits increased tyrosine phosphorylation, raising the question of whether enhanced tyrosine kinase activity is observed in prostate cancer in the absence of specific tyrosine kinase mutation or DNA amplification. We generated a mouse model of prostate cancer progression using commonly perturbed non-tyrosine kinase oncogenes and pathways and detected a significant up-regulation of tyrosine phosphorylation at the carcinoma stage. Phosphotyrosine peptide enrichment and quantitative mass spectrometry identified oncogene-specific tyrosine kinase signatures, including activation of EGFR, ephrin type-A receptor 2 (EPHA2), and JAK2. Kinase:substrate relationship analysis of the phosphopeptides also revealed ABL1 and SRC tyrosine kinase activation. The observation of elevated tyrosine kinase signaling in advanced prostate cancer and identification of specific tyrosine kinase pathways from genetically defined tumor models point to unique therapeutic approaches using tyrosine kinase inhibitors for advanced prostate cancer. PMID- 22307625 TI - Histone deacetylases 1 and 2 regulate autophagy flux and skeletal muscle homeostasis in mice. AB - Maintenance of skeletal muscle structure and function requires efficient and precise metabolic control. Autophagy plays a key role in metabolic homeostasis of diverse tissues by recycling cellular constituents, particularly under conditions of caloric restriction, thereby normalizing cellular metabolism. Here we show that histone deacetylases (HDACs) 1 and 2 control skeletal muscle homeostasis and autophagy flux in mice. Skeletal muscle-specific deletion of both HDAC1 and HDAC2 results in perinatal lethality of a subset of mice, accompanied by mitochondrial abnormalities and sarcomere degeneration. Mutant mice that survive the first day of life develop a progressive myopathy characterized by muscle degeneration and regeneration, and abnormal metabolism resulting from a blockade to autophagy. HDAC1 and HDAC2 regulate skeletal muscle autophagy by mediating the induction of autophagic gene expression and the formation of autophagosomes, such that myofibers of mice lacking these HDACs accumulate toxic autophagic intermediates. Strikingly, feeding HDAC1/2 mutant mice a high-fat diet from the weaning age releases the block in autophagy and prevents myopathy in adult mice. These findings reveal an unprecedented and essential role for HDAC1 and HDAC2 in maintenance of skeletal muscle structure and function and show that, at least in some pathological conditions, myopathy may be mitigated by dietary modifications. PMID- 22307626 TI - Antagonists of growth hormone-releasing hormone inhibit growth of androgen independent prostate cancer through inactivation of ERK and Akt kinases. AB - The management of castration-resistant prostate cancer (CRPC) presents a clinical challenge because of limitations in efficacy of current therapies. Novel therapeutic strategies for the treatment of CRPC are needed. Antagonists of hypothalamic growth hormone-releasing hormone (GHRH) inhibit growth of various malignancies, including androgen-dependent and independent prostate cancer, by suppressing diverse tumoral growth factors, especially GHRH itself, which acts as a potent autocrine/paracrine growth factor in many tumors. We evaluated the effects of the GHRH antagonist, JMR-132, on PC-3 human androgen-independent prostate cancer cells in vitro and in vivo. JMR-132 suppressed the proliferation of PC-3 cells in vitro in a dose-dependent manner and significantly inhibited growth of PC-3 tumors by 61% (P < 0.05). The expression of GHRH, GHRH receptors, and their main splice variant, SV1, in PC-3 cells and tumor xenografts was demonstrated by RT-PCR and Western blot. The content of GHRH protein in PC-3 xenografts was lowered markedly, by 66.3% (P < 0.01), after treatment with JMR 132. GHRH induced a significant increase in levels of ERK, but JMR-132 abolished this outcome. Our findings indicate that inhibition of PC-3 prostate cancer by JMR-132 involves inactivation of Akt and ERK. The inhibitory effect produced by GHRH antagonist can result in part from inactivation of the PI3K/Akt/mammalian target of rapamycin and Raf/MEK/ERK pathways and from the reduction in GHRH produced by cancer cells. Our findings support the role of GHRH as an autocrine growth factor in prostate cancer and suggest that antagonists of GHRH should be considered for further development as therapy for CRPC. PMID- 22307627 TI - Mitochondrial dysfunction and Purkinje cell loss in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). AB - Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a childhood onset neurological disease resulting from mutations in the SACS gene encoding sacsin, a 4,579-aa protein of unknown function. Originally identified as a founder disease in Quebec, ARSACS is now recognized worldwide. Prominent features include pyramidal spasticity and cerebellar ataxia, but the underlying pathology and pathophysiological mechanisms are unknown. We have generated an animal model for ARSACS, sacsin knockout mice, that display age-dependent neurodegeneration of cerebellar Purkinje cells. To explore the pathophysiological basis for this observation, we examined the cell biological properties of sacsin. We show that sacsin localizes to mitochondria in non-neuronal cells and primary neurons and that it interacts with dynamin-related protein 1, which participates in mitochondrial fission. Fibroblasts from ARSACS patients show a hyperfused mitochondrial network, consistent with defects in mitochondrial fission. Sacsin knockdown leads to an overly interconnected and functionally impaired mitochondrial network, and mitochondria accumulate in the soma and proximal dendrites of sacsin knockdown neurons. Disruption of mitochondrial transport into dendrites has been shown to lead to abnormal dendritic morphology, and we observe striking alterations in the organization of dendritic fields in the cerebellum of knockout mice that precedes Purkinje cell death. Our data identifies mitochondrial dysfunction/mislocalization as the likely cellular basis for ARSACS and indicates a role for sacsin in regulation of mitochondrial dynamics. PMID- 22307628 TI - Glycerolipid signals alter mTOR complex 2 (mTORC2) to diminish insulin signaling. AB - Increased flux through the glycerolipid synthesis pathway impairs the ability of insulin to inhibit hepatic gluconeogenesis, but the exact mechanism remains unknown. To determine the mechanism by which glycerolipids impair insulin signaling, we overexpressed glycerol-3-phosphate acyltransferase-1 (GPAT1) in primary mouse hepatocytes. GPAT1 overexpression impaired insulin-stimulated phosphorylation of Akt-S473 and -T308, diminished insulin-suppression of glucose production, significantly inhibited mTOR complex 2 (mTORC2) activity and decreased the association of mTOR and rictor. Conversely, in hepatocytes from Gpat1(-/-) mice, mTOR-rictor association and mTORC2 activity were enhanced. However, this increase in mTORC2 activity in Gpat1(-/-) hepatocytes was ablated when rictor was knocked down. To determine which lipid intermediate was responsible for inactivating mTORC2, we overexpressed GPAT1, AGPAT, or lipin to increase the cellular content of lysophosphatidic acid (LPA), phosphatidic acid (PA), or diacylglycerol (DAG), respectively. The inhibition of mTOR/rictor binding and mTORC2 activity coincided with the levels of PA and DAG species that contained 16:0, the preferred substrate of GPAT1. Furthermore, di-16:0-PA strongly inhibited mTORC2 activity and disassociated mTOR/rictor in vitro. Taken together, these data reveal a signaling pathway by which phosphatidic acid synthesized via the glycerol-3-phosphate pathway inhibits mTORC2 activity by decreasing the association of rictor and mTOR, thereby down-regulating insulin action. These data demonstrate a critical link between nutrient excess, TAG synthesis, and hepatic insulin resistance. PMID- 22307629 TI - IL-33 is processed into mature bioactive forms by neutrophil elastase and cathepsin G. AB - Interleukin-33 (IL-33) (NF-HEV) is a chromatin-associated nuclear cytokine from the IL-1 family, which has been linked to important diseases, including asthma, rheumatoid arthritis, ulcerative colitis, and cardiovascular diseases. IL-33 signals through the ST2 receptor and drives cytokine production in type 2 innate lymphoid cells (ILCs) (natural helper cells, nuocytes), T-helper (Th)2 lymphocytes, mast cells, basophils, eosinophils, invariant natural killer T (iNKT), and natural killer (NK) cells. We and others recently reported that, unlike IL-1beta and IL-18, full-length IL-33 is biologically active independently of caspase-1 cleavage and that processing by caspases results in IL-33 inactivation. We suggested that IL-33, which is released upon cellular damage, may function as an endogenous danger signal or alarmin, similar to IL-1alpha or high-mobility group box 1 protein (HMGB1). Here, we investigated the possibility that IL-33 activity may be regulated by proteases released during inflammation. Using a combination of in vitro and in vivo approaches, we demonstrate that neutrophil serine proteases cathepsin G and elastase can cleave full-length human IL-33(1-270) and generate mature forms IL-33(95-270), IL-33(99-270), and IL 33(109-270). These forms are produced by activated human neutrophils ex vivo, are biologically active in vivo, and have a ~10-fold higher activity than full-length IL-33 in cellular assays. Murine IL-33 is also cleaved by neutrophil cathepsin G and elastase, and both full-length and cleaved endogenous IL-33 could be detected in the bronchoalveolar lavage fluid in an in vivo model of acute lung injury associated with neutrophil infiltration. We propose that the inflammatory microenvironment may exacerbate disease-associated functions of IL-33 through the generation of highly active mature forms. PMID- 22307630 TI - Syndecan-4 proteoliposomes enhance fibroblast growth factor-2 (FGF-2)-induced proliferation, migration, and neovascularization of ischemic muscle. AB - Ischemia of the myocardium and lower limbs is a common consequence of arterial disease and a major source of morbidity and mortality in modernized countries. Inducing neovascularization for the treatment of ischemia is an appealing therapeutic strategy for patients for whom traditional treatment modalities cannot be performed or are ineffective. In the past, the stimulation of blood vessel growth was pursued using direct delivery of growth factors, angiogenic gene therapy, or cellular therapy. Although therapeutic angiogenesis holds great promise for treating patients with ischemia, current methods have not found success in clinical trials. Fibroblast growth factor-2 (FGF-2) was one of the first growth factors to be tested for use in therapeutic angiogenesis. Here, we present a method for improving the biological activity of FGF-2 by codelivering the growth factor with a liposomally embedded coreceptor, syndecan-4. This technique was shown to increase FGF-2 cellular signaling, uptake, and nuclear localization in comparison with FGF-2 alone. Delivery of syndecan-4 proteoliposomes also increased endothelial proliferation, migration, and angiogenic tube formation in response to FGF-2. Using an animal model of limb ischemia, syndecan-4 proteoliposomes markedly improved the neovascularization following femoral artery ligation and recovery of perfusion of the ischemic limb. Taken together, these results support liposomal delivery of syndecan-4 as an effective means to improving the potential of using growth factors to achieve therapeutic neovascularization of ischemic tissue. PMID- 22307631 TI - Using targeted transgenic reporter mice to study promoter-specific p53 transcriptional activity. AB - The p53 transcription factor modulates gene expression programs that induce cell cycle arrest, senescence, or apoptosis, thereby preventing tumorigenesis. However, the mechanisms by which these fates are selected are unclear. Our objective is to understand p53 target gene selection and, thus, enable its optimal manipulation for cancer therapy. We have generated targeted transgenic reporter mice in which EGFP expression is driven by p53 transcriptional activity at a response element from either the p21 or Puma promoter, which induces cell cycle arrest/senescence and apoptosis, respectively. We demonstrate that we could monitor p53 activity in vitro and in vivo and detect variations in p53 activity depending on the response element, tissue type, and stimulus, thereby validating our reporter system and illustrating its utility for preclinical drug studies. Our results also show that the sequence of the p53 response element itself is sufficient to strongly influence p53 target gene selection. Finally, we use our reporter system to provide evidence for p53 transcriptional activity during early embryogenesis, showing that p53 is active as early as embryonic day 3.5 and that p53 activity becomes restricted to embryonic tissue by embryonic day 6.5. The data from this study demonstrate that these reporter mice could serve as powerful tools to answer questions related to basic biology of the p53 pathway, as well as cancer therapy and drug discovery. PMID- 22307632 TI - In-feed antibiotic effects on the swine intestinal microbiome. AB - Antibiotics have been administered to agricultural animals for disease treatment, disease prevention, and growth promotion for over 50 y. The impact of such antibiotic use on the treatment of human diseases is hotly debated. We raised pigs in a highly controlled environment, with one portion of the littermates receiving a diet containing performance-enhancing antibiotics [chlortetracycline, sulfamethazine, and penicillin (known as ASP250)] and the other portion receiving the same diet but without the antibiotics. We used phylogenetic, metagenomic, and quantitative PCR-based approaches to address the impact of antibiotics on the swine gut microbiota. Bacterial phylotypes shifted after 14 d of antibiotic treatment, with the medicated pigs showing an increase in Proteobacteria (1-11%) compared with nonmedicated pigs at the same time point. This shift was driven by an increase in Escherichia coli populations. Analysis of the metagenomes showed that microbial functional genes relating to energy production and conversion were increased in the antibiotic-fed pigs. The results also indicate that antibiotic resistance genes increased in abundance and diversity in the medicated swine microbiome despite a high background of resistance genes in nonmedicated swine. Some enriched genes, such as aminoglycoside O-phosphotransferases, confer resistance to antibiotics that were not administered in this study, demonstrating the potential for indirect selection of resistance to classes of antibiotics not fed. The collateral effects of feeding subtherapeutic doses of antibiotics to agricultural animals are apparent and must be considered in cost-benefit analyses. PMID- 22307633 TI - Polar growth in the Alphaproteobacterial order Rhizobiales. AB - Elongation of many rod-shaped bacteria occurs by peptidoglycan synthesis at discrete foci along the sidewall of the cells. However, within the Rhizobiales, there are many budding bacteria, in which new cell growth is constrained to a specific region. The phylogeny of the Rhizobiales indicates that this mode of zonal growth may be ancestral. We demonstrate that the rod-shaped bacterium Agrobacterium tumefaciens grows unidirectionally from the new pole generated after cell division and has an atypical peptidoglycan composition. Polar growth occurs under all conditions tested, including when cells are attached to a plant root and under conditions that induce virulence. Finally, we show that polar growth also occurs in the closely related bacteria Sinorhizobium meliloti, Brucella abortus, and Ochrobactrum anthropi. We find that unipolar growth is an ancestral and conserved trait among the Rhizobiales, which includes important mutualists and pathogens of plants and animals. PMID- 22307634 TI - Surface multiheme c-type cytochromes from Thermincola potens and implications for respiratory metal reduction by Gram-positive bacteria. AB - Almost nothing is known about the mechanisms of dissimilatory metal reduction by Gram-positive bacteria, although they may be the dominant species in some environments. Thermincola potens strain JR was isolated from the anode of a microbial fuel cell inoculated with anaerobic digester sludge and operated at 55 degrees C. Preliminary characterization revealed that T. potens coupled acetate oxidation to the reduction of hydrous ferric oxides (HFO) or anthraquinone-2,6 disulfonate (AQDS), an analog of the redox active components of humic substances. The genome of T. potens was recently sequenced, and the abundance of multiheme c type cytochromes (MHCs) is unusual for a Gram-positive bacterium. We present evidence from trypsin-shaving LC-MS/MS experiments and surface-enhanced Raman spectroscopy (SERS) that indicates the expression of a number of MHCs during T. potens growth on either HFO or AQDS, and that several MHCs are localized to the cell wall or cell surface. Furthermore, one of the MHCs can be extracted from cells with low pH or denaturants, suggesting a loose association with the cell wall or cell surface. Electron microscopy does not reveal an S-layer, and the precipitation of silver metal on the cell surface is inhibited by cyanide, supporting the involvement of surface-localized redox-active heme proteins in dissimilatory metal reduction. These results provide unique direct evidence for cell wall-associated cytochromes and support MHC involvement in conducting electrons across the cell envelope of a Gram-positive bacterium. PMID- 22307635 TI - Reduction of dendritic spines and elevation of GABAergic signaling in the brains of mice treated with an estrogen receptor beta ligand. AB - An estrogen receptor (ER) beta ligand (LY3201) with a preference for ERbeta over ERalpha was administered in s.c. pellets releasing 0.04 mg/d. The brains of these mice were examined 3 d after treatment had begun. Although estradiol-17beta is known to increase spine density and glutaminergic signaling, as measured by Golgi staining, a clear reduction in spines was evident on the dendritic branches in LY3201-treated mice but no morphological alteration and no difference in the number of dendritic spines on dendritic stems were observed. In the LY3201 treatment group, there was higher expression of glutamic acid decarboxylase (GAD) in layer V of cortex and in the CA1 of hippocampus, more GAD(+) terminals surrounding the pyramidal neurons and less glutamate receptor (NMDAR) on the neurons in layer V. There were no alterations in expression of Iba1 or in Olig2 or CNPase. However, GFAP(+) astrocytes were increased in the LY3201-treatment group. There were also more projections characteristic of activated astrocytes and increased expression of glutamine synthetase (GS). No expression of ERbeta was detectable in the nuclei of astrocytes. Clearly, LY3201 caused a shift in the balance between excitatory and inhibitory neurotransmission in favor of inhibition. This shift was due in part to increased synthesis of GABA and increased removal of glutamate from the synaptic cleft by astrocytes. The data reveal that treatment with a selective ERbeta agonist results in changes opposite to those reported in estradiol-17beta-treated mice and suggests that ERalpha and ERbeta play opposing roles in the brain. PMID- 22307636 TI - 3beta-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders. AB - Emerging evidence suggests that the pathogenesis of depressive disorders (DDs) is associated with neuronal abnormalities in brain microtubule function, including changes in alpha-tubulin isoforms. Currently available antidepressant drugs may act by rescuing these alterations, but only after long-term treatment explaining their delayed therapeutic efficacy. The microtubule associated protein type-2 (MAP-2) modulates neuronal microtubule dynamics. Our hypothesis is that MAP-2 represents an innovative target for the treatment of DDs. The synthetic pregnenolone-derivative MAP4343 (3beta-methoxy-pregnenolone) binds MAP-2 in vitro and increases its ability to stimulate tubulin assembly. Here, we show that MAP4343 has antidepressant efficacy in rats and advantages compared with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. A single injection of MAP4343 changes the expression of alpha-tubulin isoforms indicative of increased microtubule dynamics in the hippocampus of naive Sprague-Dawley rats, whereas fluoxetine had no effects. MAP4343 has positive efficacy in the rat forced swimming test (FST), the most used assay to screen potential antidepressant drugs by decreasing immobility behavior. In the rat isolation-rearing model of depression, administration of MAP4343 showed more rapid and more persistent efficacy compared with fluoxetine in recovering "depressive-like" behaviors. These effects were accompanied by modifications of alpha-tubulin isoforms in the hippocampus, amygdala, and prefrontal cortex. Our findings suggest the potential therapeutic use of MAP4343 for the treatment of DDs, based on a unique mechanism of action. PMID- 22307637 TI - Striatum processes reward differently in adolescents versus adults. AB - Adolescents often respond differently than adults to the same salient motivating contexts, such as peer interactions and pleasurable stimuli. Delineating the neural processing differences of adolescents is critical to understanding this phenomenon, as well as the bases of serious behavioral and psychiatric vulnerabilities, such as drug abuse, mood disorders, and schizophrenia. We believe that age-related changes in the ways salient stimuli are processed in key brain regions could underlie the unique predilections and vulnerabilities of adolescence. Because motivated behavior is the central issue, it is critical that age-related comparisons of brain activity be undertaken during motivational contexts. We compared single-unit activity and local field potentials in the nucleus accumbens (NAc) and dorsal striatum (DS) of adolescent and adult rats during a reward-motivated instrumental task. These regions are involved in motivated learning, reward processing, and action selection. We report adolescent neural processing differences in the DS, a region generally associated more with learning than reward processing in adults. Specifically, adolescents, but not adults, had a large proportion of neurons in the DS that activated in anticipation of reward. More similar response patterns were observed in NAc of the two age groups. DS single-unit activity differences were found despite similar local field potential oscillations. This study demonstrates that in adolescents, a region critically involved in learning and habit formation is highly responsive to reward. It thus suggests a mechanism for how rewards might shape adolescent behavior differently, and for their increased vulnerabilities to affective disorders. PMID- 22307638 TI - Phosphatidylinositol 4-phosphate 5-kinase alpha (PIPKalpha) regulates neuronal microtubule depolymerase kinesin, KIF2A and suppresses elongation of axon branches. AB - Neuronal morphology is regulated by cytoskeletons. Kinesin superfamily protein 2A (KIF2A) depolymerizes microtubules (MTs) at growth cones and regulates axon pathfinding. The factors controlling KIF2A in neurite development remain totally elusive. Here, using immunoprecipitation with an antibody specific to KIF2A, we identified phosphatidylinositol 4-phosphate 5-kinase alpha (PIPKalpha) as a candidate membrane protein that regulates the activity of KIF2A. Yeast two-hybrid and biochemical assays demonstrated direct binding between KIF2A and PIPKalpha. Partial colocalization of the clusters of punctate signals for these two molecules was detected by confocal microscopy and photoactivated localization microscopy. Additionally, the MT-depolymerizing activity of KIF2A was enhanced in the presence of PIPKalpha in vitro and in vivo. PIPKalpha suppressed the elongation of axon branches in a KIF2A-dependent manner, suggesting a unique PIPK mediated mechanism controlling MT dynamics in neuronal development. PMID- 22307639 TI - Spatiotemporal dynamics of neocortical excitation and inhibition during human sleep. AB - Intracranial recording is an important diagnostic method routinely used in a number of neurological monitoring scenarios. In recent years, advancements in such recordings have been extended to include unit activity of an ensemble of neurons. However, a detailed functional characterization of excitatory and inhibitory cells has not been attempted in human neocortex, particularly during the sleep state. Here, we report that such feature discrimination is possible from high-density recordings in the neocortex by using 2D multielectrode arrays. Successful separation of regular-spiking neurons (or bursting cells) from fast spiking cells resulted in well-defined clusters that each showed unique intrinsic firing properties. The high density of the array, which allowed recording from a large number of cells (up to 90), helped us to identify apparent monosynaptic connections, confirming the excitatory and inhibitory nature of regular-spiking and fast-spiking cells, thus categorized as putative pyramidal cells and interneurons, respectively. Finally, we investigated the dynamics of correlations within each class. A marked exponential decay with distance was observed in the case of excitatory but not for inhibitory cells. Although the amplitude of that decline depended on the timescale at which the correlations were computed, the spatial constant did not. Furthermore, this spatial constant is compatible with the typical size of human columnar organization. These findings provide a detailed characterization of neuronal activity, functional connectivity at the microcircuit level, and the interplay of excitation and inhibition in the human neocortex. PMID- 22307640 TI - Abeta neurotoxicity depends on interactions between copper ions, prion protein, and N-methyl-D-aspartate receptors. AB - N-methyl-d-aspartate receptors (NMDARs) mediate critical CNS functions, whereas excessive activity contributes to neuronal damage. At physiological glycine concentrations, NMDAR currents recorded from cultured rodent hippocampal neurons exhibited strong desensitization in the continued presence of NMDA, thus protecting neurons from calcium overload. Reducing copper availability by specific chelators (bathocuproine disulfonate, cuprizone) induced nondesensitizing NMDAR currents even at physiologically low glycine concentrations. This effect was mimicked by, and was not additive with, genetic ablation of cellular prion protein (PrP(C)), a key copper-binding protein in the CNS. Acute ablation of PrP(C) by enzymatically cleaving its cell-surface GPI anchor yielded similar effects. Biochemical studies and electrophysiological measurements revealed that PrP(C) interacts with the NMDAR complex in a copper dependent manner to allosterically reduce glycine affinity for the receptor. Synthetic human Abeta(1-42) (10 nM-5 MUM) produced an identical effect that could be mitigated by addition of excess copper ions or NMDAR blockers. Taken together, Abeta(1-42), copper chelators, or PrP(C) inactivation all enhance the activity of glycine at the NMDAR, giving rise to pathologically large nondesensitizing steady state NMDAR currents and neurotoxicity. We propose a physiological role for PrP(C), one that limits excessive NMDAR activity that might otherwise promote neuronal damage. In addition, we provide a unifying molecular mechanism whereby toxic species of Abeta(1-42) might mediate neuronal and synaptic injury, at least in part, by disrupting the normal copper-mediated, PrP(C)-dependent inhibition of excessive activity of this highly calcium-permeable glutamate receptor. PMID- 22307641 TI - Ca2+ signaling amplification by oligomerization of L-type Cav1.2 channels. AB - Ca(2+) influx via L-type Ca(v)1.2 channels is essential for multiple physiological processes, including gene expression, excitability, and contraction. Amplification of the Ca(2+) signals produced by the opening of these channels is a hallmark of many intracellular signaling cascades, including excitation-contraction coupling in heart. Using optogenetic approaches, we discovered that Ca(v)1.2 channels form clusters of varied sizes in ventricular myocytes. Physical interaction between these channels via their C-tails renders them capable of coordinating their gating, thereby amplifying Ca(2+) influx and excitation-contraction coupling. Light-induced fusion of WT Ca(v)1.2 channels with Ca(v)1.2 channels carrying a gain-of-function mutation that causes arrhythmias and autism in humans with Timothy syndrome (Ca(v)1.2-TS) increased Ca(2+) currents, diastolic and systolic Ca(2+) levels, contractility and the frequency of arrhythmogenic Ca(2+) fluctuations in ventricular myocytes. Our data indicate that these changes in Ca(2+) signaling resulted from Ca(v)1.2-TS increasing the activity of adjoining WT Ca(v)1.2 channels. Collectively, these data support the concept that oligomerization of Ca(v)1.2 channels via their C termini can result in the amplification of Ca(2+) influx into excitable cells. PMID- 22307642 TI - Preceramic maize from Paredones and Huaca Prieta, Peru. AB - Maize (Zea mays ssp. mays) is among the world's most important and ancient domesticated crops. Although the chronology of its domestication and initial dispersals out of Mexico into Central and South America has become more clear due to molecular and multiproxy archaeobotanical research, important problems remain. Among them is the paucity of information on maize's early morphological evolution and racial diversification brought about in part by the poor preservation of macrofossils dating to the pre-5000 calibrated years before the present period from obligate dispersal routes located in the tropical forest. We report newly discovered macrobotanical and microbotanical remains of maize that shed significant light on the chronology, land race evolution, and cultural contexts associated with the crop's early movements into South America and adaptation to new environments. The evidence comes from the coastal Peruvian sites of Paredones and Huaca Prieta, Peru; dates from the middle and late preceramic and early ceramic periods (between ca. 6700 and 3000 calibrated years before the present); and constitutes some of the earliest known cobs, husks, stalks, and tassels. The macrobotanical record indicates that a diversity of racial complexes characteristic of the Andean region emerged during the preceramic era. In addition, accelerator mass spectrometry radiocarbon determinations carried out directly on different structures of preserved maize plants strongly suggest that assays on burned cobs are more reliable than those on unburned cobs. Our findings contribute to knowledge of the early diffusion of maize and agriculture and have broader implications for understanding the development of early preindustrial human societies. PMID- 22307643 TI - CLE-like (CLEL) peptides control the pattern of root growth and lateral root development in Arabidopsis. AB - CLE peptides, named for the CLV3/ESR-related peptide family, participate in intercellular-signaling pathways. Here we investigated members of the CLE-like (CLEL) gene family that encode peptide precursors recently designated as root growth factors [Matsuzaki Y et al. (2010) Science 329:1065-1067]. CLEL precursors share a similar domain structure with CLE precursors (i.e., they contain a putative N-terminal signal peptide and a C-terminal conserved 13-amino-acid CLEL motif with a variable middle portion). Our evidence shows that, unlike root growth factor, CLEL peptides are (i) unmodified and (ii) function in the regulation of the direction of root growth and lateral root development. Overexpression of several CLEL genes in Arabidopsis resulted in either long roots or long and wavy roots that also showed altered lateral root patterning. Exogenous application of unmodified synthetic 13-amino-acid peptides derived from two CLEL motifs resulted in similar phenotypic changes in roots of wild-type plants. In CLEL peptide-induced long roots, the root apical meristem (RAM) was enlarged and consisted of an increased number of cells, compared with wild-type root apical meristems. The wavy-root phenotype appeared to be independent of other responses of the roots to the environment (e.g., gravitropism, phototropism, and thigmotropism). Results also showed that the inhibition of lateral initiation by CLEL overexpression was not overcome by the application of auxin. These findings establish CLEL as a peptide family with previously unrecognized regulatory functions controlling the pattern of root growth and lateral root development in plants. PMID- 22307644 TI - MtPAR MYB transcription factor acts as an on switch for proanthocyanidin biosynthesis in Medicago truncatula. AB - MtPAR (Medicago truncatula proanthocyanidin regulator) is an MYB family transcription factor that functions as a key regulator of proanthocyanidin (PA) biosynthesis in the model legume Medicago truncatula. MtPAR expression is confined to the seed coat, the site of PA accumulation. Loss-of-function par mutants contained substantially less PA in the seed coat than the wild type, whereas levels of anthocyanin and other specialized metabolites were normal in the mutants. In contrast, massive accumulation of PAs occurred when MtPAR was expressed ectopically in transformed hairy roots of Medicago. Transcriptome analysis of par mutants and MtPAR-expressing hairy roots, coupled with yeast one hybrid analysis, revealed that MtPAR positively regulates genes encoding enzymes of the flavonoid-PA pathway via a probable activation of WD40-1. Expression of MtPAR in the forage legume alfalfa (Medicago sativa) resulted in detectable levels of PA in shoots, highlighting the potential of this gene for biotechnological strategies to increase PAs in forage legumes for reduction of pasture bloat in ruminant animals. PMID- 22307645 TI - A polymer of caffeyl alcohol in plant seeds. AB - Lignins are complex phenylpropanoid polymers mostly associated with plant secondary cell walls. Lignins arise primarily via oxidative polymerization of the three monolignols, p-coumaryl, coniferyl, and sinapyl alcohols. Of the two hydroxycinnamyl alcohols that represent incompletely methylated biosynthetic products (and are not usually considered to be monolignols), 5-hydroxyconiferyl alcohol is now well established as incorporating into angiosperm lignins, but incorporation of caffeyl alcohol has not been shown. We report here the presence of a homopolymer of caffeyl alcohol in the seed coats of both monocot and dicot plants. This polymer (C-lignin) is deposited to high concentrations in the seed coat during the early stages of seed development in the vanilla orchid (Vanilla planifolia), and in several members of the Cactaceae. The lignin in other parts of the Vanilla plant is conventionally biosynthesized from coniferyl and sinapyl alcohols. Some species of cacti contain only C-lignin in their seeds, whereas others contain only classical guaiacyl/syringyl lignin (derived from coniferyl and sinapyl alcohols). NMR spectroscopic analysis revealed that the Vanilla seed coat polymer was massively comprised of benzodioxane units and was structurally similar to the polymer synthesized in vitro by peroxidase-catalyzed polymerization of caffeyl alcohol. CD spectroscopy did not detect any optical activity in the seed polymer. These data support the contention that the C-lignin polymer is produced in vivo via combinatorial oxidative radical coupling that is under simple chemical control, a mechanism analogous to that theorized for classical lignin biosynthesis. PMID- 22307646 TI - Qa-SNAREs localized to the trans-Golgi network regulate multiple transport pathways and extracellular disease resistance in plants. AB - In all eukaryotic cells, a membrane-trafficking system connects the post-Golgi organelles, such as the trans-Golgi network (TGN), endosomes, vacuoles, and the plasma membrane. This complex network plays critical roles in several higher order functions in multicellular organisms. The TGN, one of the important organelles for protein transport in the post-Golgi network, functions as a sorting station, where cargo proteins are directed to the appropriate post-Golgi compartments. Unlike its roles in animal and yeast cells, the TGN has also been reported to function like early endosomal compartments in plant cells. However, the physiological roles of the TGN functions in plants are not understood. Here, we report a study of the SYP4 group (SYP41, SYP42, and SYP43), which represents the plant orthologs of the Tlg2/syntaxin16 Qa-SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) that localizes on the TGN in yeast and animal cells. The SYP4 group regulates the secretory and vacuolar transport pathways in the post-Golgi network and maintains the morphology of the Golgi apparatus and TGN. Consistent with a secretory role, SYP4 proteins are required for extracellular resistance responses to a fungal pathogen. We also reveal a plant cell-specific higher-order role of the SYP4 group in the protection of chloroplasts from salicylic acid-dependent biotic stress. PMID- 22307647 TI - MicroRNA regulation of plant innate immune receptors. AB - Plant genomes contain large numbers of cell surface leucine-rich repeat (LRR) and intracellular nucleotide binding (NB)-LRR immune receptors encoded by resistance (R) genes that recognize specific pathogen effectors and trigger resistance responses. The unregulated expression of NB-LRR genes can trigger autoimmunity in the absence of pathogen infection and inhibit plant growth. Despite the potential serious consequence on agricultural production, the mechanisms regulating R-gene expression are not well understood. We identified microRNA (miRNA) progenitor genes precursor transcripts, and two miRNAs [nta-miR6019 (22-nt) and nta-miR6020 (21-nt)] that guide cleavage of transcripts of the Toll and Interleukin-1 receptor-NB-LRR immune receptor N from tobacco that confers resistance to tobacco mosaic virus (TMV). We further showed that cleavage by nta-miR6019 triggers RNA dependent RNA polymerase 6- and ribonuclease Dicer-like 4-dependent biogenesis of 21-nt secondary siRNAs "in phase" with the 22-nt miR6019 cleavage site. Furthermore, we found that processing of the 22-nt nta-miR6019 depended on an asymmetric bulge caused by mismatch in the nta-miR6019 precursor. Interestingly, coexpression of N with nta-miR6019 and nta-miR6020 resulted in attenuation of N mediated resistance to TMV, indicating that these miRNAs have functional roles in NB-LRR regulation. Using a bioinformatics approach, we identified six additional 22-nt miRNA and two 21-nt miRNA families from three Solanaceae species-tobacco, tomato, and potato. We show that members of these miRNA families cleave transcripts of predicted functional R genes and trigger production of phased secondary 21-nt siRNAs. Our results demonstrate a conserved role for miRNAs and secondary siRNAs in NB-LRR/LRR immune receptor gene regulation and pathogen resistance in Solanaceae. PMID- 22307648 TI - Retinotopic memory is more precise than spatiotopic memory. AB - Successful visually guided behavior requires information about spatiotopic (i.e., world-centered) locations, but how accurately is this information actually derived from initial retinotopic (i.e., eye-centered) visual input? We conducted a spatial working memory task in which subjects remembered a cued location in spatiotopic or retinotopic coordinates while making guided eye movements during the memory delay. Surprisingly, after a saccade, subjects were significantly more accurate and precise at reporting retinotopic locations than spatiotopic locations. This difference grew with each eye movement, such that spatiotopic memory continued to deteriorate, whereas retinotopic memory did not accumulate error. The loss in spatiotopic fidelity is therefore not a generic consequence of eye movements, but a direct result of converting visual information from native retinotopic coordinates. Thus, despite our conscious experience of an effortlessly stable spatiotopic world and our lifetime of practice with spatiotopic tasks, memory is actually more reliable in raw retinotopic coordinates than in ecologically relevant spatiotopic coordinates. PMID- 22307649 TI - Noninvasive inference of the molecular chemotactic response using bacterial trajectories. AB - The quality of sensing and response to external stimuli constitutes a basic element in the selective performance of living organisms. Here we consider the response of Escherichia coli to chemical stimuli. For moderate amplitudes, the bacterial response to generic profiles of sensed chemicals is reconstructed from its response function to an impulse, which then controls the efficiency of bacterial motility. We introduce a method for measuring the impulse response function based on coupling microfluidic experiments and inference methods: The response function is inferred using Bayesian methods from the observed trajectories of bacteria swimming in microfluidically controlled chemical fields. The notable advantages are that the method is based on the bacterial swimming response, it is noninvasive, without any genetic and/or mechanical preparation, and assays the behavior of the whole flagella bundle. We exploit the inference method to measure responses to aspartate and alpha-methylaspartate--measured previously by other methods--as well as glucose, leucine, and serine. The response to the attractant glucose is shown to be biphasic and perfectly adapted, as for aspartate. The response to the attractant serine is shown to be biphasic yet imperfectly adapted, that is, the response function has a nonzero (positive) integral. The adaptation of the response to the repellent leucine is also imperfect, with the sign of the two phases inverted with respect to serine. The diversity in the bacterial population of the response function and its dependency upon the background concentration are quantified. PMID- 22307650 TI - Femtosecond laser vaporization that preserves protein-folded structure: an unproven idea. PMID- 22307651 TI - Are low-frequency songs sexually selected, and do they lose their potency in male female interactions under noisy conditions? PMID- 22307653 TI - Isolation of alpha-glucuronidase enzyme from a rumen metagenomic library. AB - alpha-Glucuronidase enzymes play an essential role in the full enzymatic hydrolysis of hemicellulose. Up to this point, all genes encoding alpha glucuronidase enzymes have been cloned from individual, pure culture strains. Using a high-throughput screening strategy, we have isolated the first alpha glucuronidase gene (rum630-AG) from a mixed population of microorganisms. The gene was subcloned into a prokaryotic vector, and the enzyme was overexpressed and biochemically characterized. The RUM630-AG enzyme had optimum activity at pH 6.5 and 40 degrees C. When birchwood xylan was used as substrate, the RUM630-AG functioned synergistically with an endoxylanase enzyme to hydrolyze the substrate. PMID- 22307652 TI - Distinct energy metabolism of auditory and vestibular sensory epithelia revealed by quantitative mass spectrometry using MS2 intensity. AB - Measuring the abundance of many proteins over a broad dynamic range requires accurate quantitation. We show empirically that, in MS experiments, relative quantitation using summed dissociation-product ion-current intensities is accurate, albeit variable from protein to protein, and outperforms spectral counting. By applying intensities to quantify proteins in two complex but related tissues, chick auditory and vestibular sensory epithelia, we find that glycolytic enzymes are enriched threefold in auditory epithelia, whereas enzymes responsible for oxidative phosphorylation are increased at least fourfold in vestibular epithelia. This striking difference in relative use of the two ATP-production pathways likely reflects the isolation of the auditory epithelium from its blood supply, necessary to prevent heartbeat-induced mechanical disruptions. The global view of protein expression afforded by label-free quantitation with a wide dynamic range reveals molecular specialization at a tissue or cellular level. PMID- 22307654 TI - High-level expression, purification, characterization and structural prediction of a snake venom metalloproteinase inhibitor in Pichia pastoris. AB - Snake venom metalloproteinase inhibitor BJ46a is from the serum of the venomous snake Bothrops jararaca. It has been proven to possess the capacity to inhibit matrix metalloproteinases (MMPs), likely based on its structural similarity to MMPs. This report describes the successful expression, purification, and characterization of the recombinant protein BJ46a in Pichia pastoris. Purified recombinant protein BJ46a was found to inhibit MMPs. Structural modeling was completed and should provide the foundation for further functional research. To our knowledge, this is the first report on the large scale expression of BJ46a, and it provides promise as a method for generation of BJ46a and investigation of its potential use as a new drug for treatment of antitumor invasion and metastasis. PMID- 22307656 TI - Viral safety in the 21st century. PMID- 22307655 TI - Microbial exposures in infancy predict levels of the immunoregulatory cytokine interleukin-4 in Filipino young adults. AB - OBJECTIVES: Infancy represents a window of development during which long-term immunological functioning can be influenced. In this study, we evaluate proxies of microbial exposures in infancy as predictors of interleukin-4 (IL-4) in young adulthood. IL-4 is an immunoregulatory cytokine that plays a role in the pathogenesis of atopic and allergic diseases. METHODS: Data were obtained from 1,403 participants in the Cebu Longitudinal Health and Nutrition Survey, an ongoing population-based study in the Philippines. Relationships between microbial and nutritional environments in infancy and plasma IL-4 concentrations in adulthood were evaluated using tobit regression models. RESULTS: Having older siblings and more episodes of respiratory illness in infancy significantly predicted lower concentrations of plasma IL-4 in adulthood. Unexpectedly, more episodes of diarrheal illness in infancy were associated with higher IL-4 in adulthood. Interactions between a composite household pathogen exposure score and the duration of exclusive breastfeeding approached significance. This interaction showed that the negative association between household pathogen exposure in infancy and adult IL-4 was only significant for individuals who had been exclusively breastfed for a short duration of time. Finally, currently living in an urban household was unexpectedly, negatively associated with adult IL-4. Associations were independent of early nutrition, socioeconomic status (SES), and urbanicity, as well as current measures of infection, body fat, SES, and smoking. CONCLUSIONS: This study builds on a growing body of literature demonstrating that early ecological conditions have long-term effects on human biology by providing evidence that multiple proxies of microbial exposures in infancy are associated with adult IL-4. PMID- 22307657 TI - Inhibition of tungsten-induced protein aggregation by cetyl trimethyl ammonium bromide. AB - TECHNICAL ABSTRACT: The purpose of this work was to investigate a potential mechanism for the inhibition of tungsten-mediated monoclonal antibody (mAb) biophysical modifications and sub-visible particle formation. A 1 mg/mL mAb formulated in 150 mM NaCl, 20 mM histidine, pH 6.0, was incubated with 1, 37, and 100 ppm of tungsten polyanions in the form of sodium tungstate both in the presence and absence of the anionic surfactant and chelating agent diethylene triamine pentaacetic acid (DTPA) or the cationic surfactant cetyl trimethyl ammonium bromide (CTAB) for 24 h at 25 degrees C. Assays including pH, UV-Vis spectroscopy, size exclusion chromatography, intrinsic tryptophan/tyrosine fluorescence, and micro-flow imaging were performed to assess the impact on short term mAb stability and aggregation. We conclude that the use of micromolar concentrations of the formulation excipient and cationic surfactant CTAB equivalent to the anticipated tungsten concentration in solution effectively inhibits loss of protein concentration, fragmentation, changes in intrinsic fluorescence intensity, and the formation of sub-visible particles. LAY ABSTRACT: The purpose of this work was to investigate a potential mechanism for the inhibition of tungsten-mediated monoclonal antibody (mAb) biophysical modifications and sub-visible particle formation. A mAb formulation was incubated with tungsten polyanions in the presence and absence of the anionic surfactant and chelating agent diethylene triamine pentaacetic acid (DTPA) or the cationic surfactant cetyl trimethyl ammonium bromide (CTAB). Formulation was characterized by pH, UV-Vis spectroscopy, size exclusion chromatography, intrinsic tryptophan/tyrosine fluorescence, and micro-flow imaging. We conclude that the formulation excipient and cationic surfactant CTAB effectively inhibits biophysical modifications and sub-visible particle formation. PMID- 22307658 TI - Interactions between Therapeutic Proteins and Acrylic Acid Leachable. AB - Leachables are chemical compounds that migrate from manufacturing equipment, primary containers and closure systems, and packaging components into biopharmaceutical and pharmaceutical products. Acrylic acid (at concentration around 5 MUg/mL) was detected as leachable in syringes from one of the potential vendors (X syringes). In order to evaluate the potential impact of acrylic acid on therapeutic proteins, an IgG 2 molecule was filled into a sterilized X syringe and then incubated at 45 degrees C for 45 days in a pH 5 acetate buffer. We discovered that acrylic acid can interact with proteins at three different sites: (1) the lysine side chain, (2) the N-terminus, and (3) the histidine side chain, by the Michael reaction. In this report, the direct interactions between acrylic acid leachable and a biopharmaceutical product were demonstrated and the reaction mechanism was proposed. Even thought a small amount (from 0.02% to 0.3%) of protein was found to be modified by acrylic acid, the modified protein can potentially be harmful due to the toxicity of acrylic acid. After being modified by acrylic acid, the properties of the therapeutic protein may change due to charge and hydrophobicity variations. LAY ABSTRACT: Acrylic acid was detected to migrate from syringes (Vendor X) into a therapeutic protein solution (at a concentration around 5 MUg/mL). In this study, we discovered that acrylic acid can modify proteins at three different sites: (1) the lysine side chain, 2) the N terminus, and 3) the histidine side chain, by the Michael reaction. In this report, the direct interactions between acrylic acid leachable and a biopharmaceutical product were demonstrated and the reaction mechanism was proposed. PMID- 22307659 TI - Evaluation of the Discrepancy between the European Pharmacopoeia Test and an Adopted United States Pharmacopoeia Test Regarding the Weight Uniformity of Scored Tablet Halves: Is Harmonization Required? AB - The aim of this study was to evaluate whether there exists any discrepancy between the European Pharmacopoeia (Ph. Eur.) and adopted United States Pharmacopeia (USP) tests concerning the weight uniformity measurements of tablet halves after splitting. The USP method does not contain provisions to evaluate split tablets, so here we adopt their whole tablet weight uniformity method. Twenty-nine different commercial scored tablets (local and imported) were divided. The split units were individually weighed and the relative standard deviation (RSD) for each product was calculated and then evaluated according to both the adopted USP and the Ph. Eur. tests of weight uniformity. Twenty out of the 29 products tested failed the USP test, while 14 of them failed the Ph. Eur. test. Nine products passed both the USP and Ph. Eur. tests. Six products passed the Ph. Eur. test but failed the USP test, with all of these products having an RSD greater than 6%. The correlation coefficient between the weight and content of split halves for three randomly selected products-corotenol 100 mg, corotenol 50 mg, and lorazepam 2.5 mg-was found to be 0.986, 0.998, and 0.72, respectively. A clear difference can be seen between outcomes obtained by the two compendial tablet splitting methods with regard to weight uniformity. Results from the USP test showed that tighter measures are needed to pass the test. Our results argue that the Ph. Eur. should revise the existing weight uniformity test on scored tablets to include the RSD parameter in it. The USP should include this adopted test as a specific test for scored tablet halves, not just whole tablets. Manufacturers in some cases will need to improve the quality of the produced scored tablets in order to pass the USP test, especially those with low therapeutic indices. Finally, harmonization between the pharmacopoeias regarding the weight uniformity testing of split tablets is warranted. LAY ABSTRACT: The aim of this study was to evaluate whether there exists any difference between the European Pharmacopoeia (Ph. Eur.) and adopted United States Pharmacopeia (USP) methods to evaluate weight uniformity when drug tablets are split. The USP method does not contain provisions to evaluate split tablets, so here we adopt their whole tablet weight uniformity method. Twenty-nine different commercial scored tablets were obtained and divided. The split units were individually weighed and the relative standard deviation (RSD) of the split tablets for each product was calculated and then evaluated according to both methods. Twenty out of the 29 products tested failed the USP method, while 14 of them failed the Ph. Eur. method. Six products passed the Ph. Eur. test but failed the USP test because these products had an RSD greater than 6%. A clear difference can be seen between the pass/fail results of tablet splitting obtained by the two methods. The USP test showed that tighter measures are needed for products to pass the test. We recommend that the Ph. Eur. include the RSD parameter in it to make the method more rigorous. The USP is also recommended to include this adopted test as a specific test for scored tablet halves, not just for whole tablets. In the cases where the tablets failed either test, manufacturers should improve the quality of the produced scored tablets. Finally, using the same weight uniformity method by all pharmacopoeias is recommended. PMID- 22307660 TI - Formulation and pharmacokinetics of diclofenac lipid nanoemulsions for parenteral application. AB - The objective of the present study was to formulate and determine the pharmacokinetics of stable o/w parenteral lipid nanoemulsions (LNEs) of diclofenac acid used to treat arthritic conditions. The LNEs of diclofenac acid with a mean size ranging from 200 to 240 nm and a zeta potential of -29.4 +/- 1.04 mV (negatively charged LNEs) and 62.1 +/- 3.5 (positively charged LNEs) emulsions were prepared by hot homogenization and ultrasonication process. The influence of formulation variables, such as the change in proportion of cholesterol, was studied, and optimized formulations were developed. The optimized formulations were relatively stable during centrifugal stress, dilution stress, and storage. The drug content and entrapment efficiency were determined using high-performance liquid chromatography. The in vitro drug release was carried out in phosphate-buffered saline pH 7.4 and cumulative amount of drug released was estimated using a UV-visible spectro-photometer. During in vivo pharmacokinetic studies in male Wistar rats, diclofenac serum concentration from LNEs was higher than that of Voveran injection and was detectable up to 12 h. Diclofenac in LNEs showed improved pharmacokinetic profile with increase in area under the curve, elimination half-life and mean residence time in comparison to Voveran. LAY ABSTRACT: Our aim was to prepare and determine the pharmacokinetics of injectable lipid nanoemulsions of diclofenac acid for treating arthritic conditions by reducing the frequency of dosing and pain at site of injection. The nanoemulsions of diclofenac acid were prepared by homogenization and ultrasonication process. The sizes and charges of oil globules were determined. The effect of cholesterol on stability of emulsion was studied, and an optimized preparation was developed. The optimized formulations were stable during centrifugation, dilution, and storage. The total amount of drug in emulsion and percentage amount of drug present in emulsion globules were determined using high performance liquid chromatography. The drug release from preparation was carried out in phosphate-buffered saline pH 7.4. The cumulative amount of drug released was estimated using a spectrophotometer. The time course of the released drug in rat serum was determined. Diclofenac concentrations from lipid nanoemulsions were higher than that of Voveran injection (solution form) in serum. PMID- 22307661 TI - Validation of the BacT/ALERT(R) 3D System for Rapid Sterility Testing of Biopharmaceutical Samples. AB - The BacT/ALERT(r) 3D system was validated to determine the sterility of different types of biopharmaceutical samples such as water for injection, unprocessed bulk, and finished bulk. The installation, operation, and performance qualification were completed and verified under good manufacturing practices. During the installation and operation validation stages, the functionality and security of the system and software were completed and verified. For the performance qualification, 11 microorganisms were evaluated, six compendial (Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Candida albicans, Aspergillus niger, Clostridium sporogenes), one representing the number one microbial species in sterile product recalls (Burkholderia cepacia), and four environmental isolates (Kocuria rhizophila, Staphylococcus haemolyticus, Methylobacterium radiotolerans, and Penicillium spp.). Nine of the microorganisms were spiked into three different types of biopharmaceutical samples by three different analysts on different days to ascertain the equivalence, ruggedness, sensitivity, time of detection, and repeatability. In all samples, the BacT/ALERT(r) exhibited equivalent or better detection than the standard test. With the exception of M. radiotolerans, all 11 microorganisms were detected within 2.5 days using the BacT/ALERT(r) system and the standard test. The detection times for M. radiotolerans in the three sample types averaged 5.77 days. The minimum detectable level of cells for all the microorganisms tested was found to be within 1 to 2 CFU. The system optimized sterility testing by the simultaneous on-line, non-destructive incubation and detection of microbial growth. PMID- 22307662 TI - Effects of subzero temperature exposure and supercooling on glass vial breakage: risk management and other applications in cold chain distribution. AB - During the distribution of temperature-sensitive products (cold chain distribution), unintentional exposure of typical glass drug vials to subzero (below 0 degrees C) temperatures introduces potential risks of glass vial breakage during freeze (as well as thaw) and potential destabilizing effects of any biologic or pharmaceutical contained within. Vial breakage during freezing not only leads to product loss, but also to potential safety/sterility issues. This paper focuses on the physical aspects of tested glass vials as well as thermodynamic behaviors observed (specifically supercooling) in liquid product. In this study, filled glass vials varying from 5 to 500 mL were subjected to specific temperature levels (-15, -10, and -6 degrees C) in controlled chambers. Thermocouples were used to record temperatures within various probed vials and the ambient temperature of the controlled chamber. Vials were visually inspected for cracks/fractures after every cycle of conditioning. Samples of the cracked and non-cracked vials were sent to a third party glass analysis laboratory for further observations. This study provides insight into the physical impact of exposing filled glass vials to subzero temperatures for short durations commonly observed during cold chain distribution. PMID- 22307663 TI - Essential Aspects in Assessing the Safety Impact of Interactions between a Drug Product and Its Associated Manufacturing System. AB - An emerging trend in the biotechnology industry is the utilization of plastic components in manufacturing systems for the production of an active pharmaceutical ingredient (API) or a finished drug product (FDP). If the API, the FDP, or any solution used to generate them (for example, process streams such as media, buffers, and the like) come in contact with a plastic at any time during the manufacturing process, there is the potential that substances leached from the plastic may accumulate in the API or FDP, affecting safety and/or efficacy. In this article the author develops a terminology that addresses process streams associated with the manufacturing process. Additionally, the article outlines the safety assessment process for manufacturing systems, specifically addressing the topics of risk management and the role of compendial testing. Finally, the proper use of vendor-supplied extractables information is considered. LAY ABSTRACT: Manufacturing suites used to produce biopharmaceuticals can include components that are made out of plastics. Thus it is possible that substances could leach out of the plastics and into manufacturing solutions, and it is further possible that such leachables could accumulate in the pharmaceutical product. In this article, the author develops a terminology that addresses process streams associated with the manufacturing process. Additionally, the author proposes a process by which the impact on product safety of such leached substances can be assessed. PMID- 22307664 TI - Probability concepts in quality risk management. AB - Essentially any concept of risk is built on fundamental concepts of chance, likelihood, or probability. Although risk is generally a probability of loss of something of value, given that a risk-generating event will occur or has occurred, it is ironic that the quality risk management literature and guidelines on quality risk management tools are relatively silent on the meaning and uses of "probability." The probability concept is typically applied by risk managers as a combination of frequency-based calculation and a "degree of belief" meaning of probability. Probability as a concept that is crucial for understanding and managing risk is discussed through examples from the most general, scenario defining and ranking tools that use probability implicitly to more specific probabilistic tools in risk management. A rich history of probability in risk management applied to other fields suggests that high-quality risk management decisions benefit from the implementation of more thoughtful probability concepts in both risk modeling and risk management. LAY ABSTRACT: Essentially any concept of risk is built on fundamental concepts of chance, likelihood, or probability. Although "risk" generally describes a probability of loss of something of value, given that a risk-generating event will occur or has occurred, it is ironic that the quality risk management literature and guidelines on quality risk management methodologies and respective tools focus on managing severity but are relatively silent on the in-depth meaning and uses of "probability." Pharmaceutical manufacturers are expanding their use of quality risk management to identify and manage risks to the patient that might occur in phases of the pharmaceutical life cycle from drug development to manufacture, marketing to product discontinuation. A probability concept is typically applied by risk managers as a combination of data-based measures of probability and a subjective "degree of belief" meaning of probability. Probability as a concept that is crucial for understanding and managing risk is discussed through examples from the most general, scenario defining and ranking tools that use probability implicitly to more specific probabilistic tools in risk management. PMID- 22307665 TI - Remodeling of the peripheral cardiac conduction system in response to pressure overload. AB - How chronic pressure overload affects the Purkinje fibers of the ventricular peripheral conduction system (PCS) is not known. Here, we used a connexin (Cx)40 knockout/enhanced green fluorescent protein knockin transgenic mouse model to specifically label the PCS. We hypothesized that the subendocardially located PCS would remodel after chronic pressure overload and therefore analyzed cell size, markers of hypertrophy, and PCS-specific Cx and ion channel expression patterns. Left ventricular hypertrophy with preserved systolic function was induced by 30 days of surgical transaortic constriction. After transaortic constriction, we observed that PCS cardiomyocytes hypertrophied by 23% (P < 0.05) and that microdissected PCS tissue exhibited upregulated markers of hypertrophy. PCS cardiomyocytes showed a 98% increase in the number of Cx40-positive gap junction particles, with an associated twofold increase in gene expression (P < 0.05). We also identified a 50% reduction in Cx43 gap junction particles located at the interface between PCS cardiomyocytes and the working cardiomyocyte. In addition, we measured a fourfold increase of an ion channel, hyperpolarization-activated cyclic nucleotide-gated channel (HCN)4, throughout the PCS (P < 0.05). As a direct consequence of PCS remodeling, we found that pressure-overloaded hearts exhibited marked changes in ventricular activation patterns during normal sinus rhythm. These novel findings characterize PCS cardiomyocyte remodeling after chronic pressure overload. We identified significant hypertrophic growth accompanied by modified expression of Cx40, Cx43, and HCN4 within PCS cardiomyocytes. We found that a functional outcome of these changes is a failure of the PCS to activate the ventricular myocardium normally. Our findings provide a proof of concept that pressure overload induces specific cellular changes, not just within the working myocardium but also within the specialized PCS. PMID- 22307666 TI - Adrenomedullin-epinephrine cotreatment enhances cardiac output and left ventricular function by energetically neutral mechanisms. AB - Adrenomedullin (AM) used therapeutically reduces mortality in the acute phase of experimental myocardial infarction. However, AM is potentially deleterious in acute heart failure as it is vasodilative and inotropically neutral. AM and epinephrine (EPI) are cosecreted from chromaffin cells, indicating a physiological interaction. We assessed the hemodynamic and energetic profile of AM-EPI cotreatment, exploring whether drug interaction improves cardiac function. Left ventricular (LV) mechanoenergetics were evaluated in 14 open-chest pigs using pressure-volume analysis and the pressure-volume area-myocardial O(2) consumption (PVA-MVo(2)) framework. AM (15 ng.kg(-1).min(-1), n = 8) or saline (controls, n = 6) was infused for 120 min. Subsequently, a concurrent infusion of EPI (50 ng.kg(-1).min(-1)) was added in both groups (AM-EPI vs. EPI). AM increased cardiac output (CO) and coronary blood flow by 20 +/- 10% and 39 +/- 14% (means +/- SD, P < 0.05 vs. baseline), whereas controls were unaffected. AM EPI increased CO and coronary blood flow by 55 +/- 17% and 75 +/- 16% (P < 0.05, AM-EPI interaction) compared with 13 +/- 12% (P < 0.05 vs. baseline) and 18 +/- 31% (P = not significant) with EPI. LV systolic capacitance decreased by -37 +/- 22% and peak positive derivative of LV pressure (dP/dt(max)) increased by 32 +/- 7% with AM-EPI (P < 0.05, AM-EPI interaction), whereas no significant effects were observed with EPI. Mean arterial pressure was maintained by AM-EPI and tended to decrease with EPI (+2 +/- 13% vs. -11 +/- 10%, P = not significant). PVA-MVo(2) relationships were unaffected by all treatments. In conclusion, AM-EPI cotreatment has an inodilator profile with CO and LV function augmented beyond individual drug effects and is not associated with relative increases in energetic cost. This can possibly take the inodilator treatment strategy beyond hemodynamic goals and exploit the cardioprotective effects of AM in acute heart failure. PMID- 22307667 TI - Assessing left ventricular systolic dysfunction after myocardial infarction: are ejection fraction and dP/dt(max) complementary or redundant? AB - Among the various cardiac contractility parameters, left ventricular (LV) ejection fraction (EF) and maximum dP/dt (dP/dt(max)) are the simplest and most used. However, these parameters are often reported together, and it is not clear if they are complementary or redundant. We sought to compare the discriminative value of EF and dP/dt(max) in assessing systolic dysfunction after myocardial infarction (MI) in swine. A total of 220 measurements were obtained. All measurements included LV volumes and EF analysis by left ventriculography, invasive ventricular pressure tracings, and echocardiography. Baseline measurements were performed in 132 pigs, and 88 measurements were obtained at different time points after MI creation. Receiver operator characteristic (ROC) curves to distinguish the presence or absence of an MI revealed a good predictive value for EF [area under the curve (AUC): 0.998] but not by dP/dt(max) (AUC: 0.69, P < 0.001 vs. EF). Dividing dP/dt(max) by LV end-diastolic pressure and heart rate (HR) significantly increased the AUC to 0.87 (P < 0.001 vs. dP/dt(max) and P < 0.001 vs. EF). In naive pigs, the coefficient of variation of dP/dt(max) was twice than that of EF (22.5% vs. 9.5%, respectively). Furthermore, in n = 19 pigs, dP/dt(max) increased after MI. However, echocardiographic strain analysis of 23 pigs with EF ranging only from 36% to 40% after MI revealed significant correlations between dP/dt(max) and strain parameters in the noninfarcted area (circumferential strain: r = 0.42, P = 0.05; radial strain: r = 0.71, P < 0.001). In conclusion, EF is a more accurate measure of systolic dysfunction than dP/dt(max) in a swine model of MI. Despite the variability of dP/dt(max) both in naive pigs and after MI, it may sensitively reflect the small changes of myocardial contractility. PMID- 22307668 TI - Electromechanical and structural alterations in the aging rabbit heart and aorta. AB - Aging increases the risk for arrhythmias and sudden cardiac death (SCD). We aimed at elucidating aging-related electrical, functional, and structural changes in the heart and vasculature that account for this heightened arrhythmogenic risk. Young (5-9 mo) and old (3.5-6 yr) female New Zealand White (NZW) rabbits were subjected to in vivo hemodynamic, electrophysiological, and echocardiographic studies as well as ex vivo optical mapping, high-field magnetic resonance imaging (MRI), and histochemical experiments. Aging increased aortic stiffness (baseline pulse wave velocity: young, 3.54 +/- 0.36 vs. old, 4.35 +/- 0.28 m/s, P < 0.002) and diastolic (end diastolic pressure-volume relations: 3.28 +/- 0.5 vs. 4.95 +/- 1.5 mmHg/ml, P < 0.05) and systolic (end systolic pressure-volume relations: 20.56 +/- 4.2 vs. 33.14 +/- 8.4 mmHg/ml, P < 0.01) myocardial elastances in old rabbits. Electrophysiological and optical mapping studies revealed age-related slowing of ventricular and His-Purkinje conduction (His-to-ventricle interval: 23 +/- 2.5 vs. 31.9 +/- 2.9 ms, P < 0.0001), altered conduction anisotropy, and a greater inducibility of ventricular fibrillation (VF, 3/12 vs. 7/9, P < 0.05) in old rabbits. Histochemical studies confirmed an aging-related increased fibrosis in the ventricles. MRI showed a deterioration of the free-running Purkinje fiber network in ventricular and septal walls in old hearts as well as aging-related alterations of the myofibrillar orientation and myocardial sheet structure that may account for this slowed conduction velocity. Aging leads to parallel stiffening of the aorta and the heart, including an increase in systolic stiffness and contractility and diastolic stiffness. Increasingly, anisotropic conduction velocity due to fibrosis and altered myofibrillar orientation and myocardial sheet structure may contribute to the pathogenesis of VF in old hearts. The aging rabbit model represents a useful tool for elucidating age related changes that predispose the aging heart to arrhythmias and SCD. PMID- 22307669 TI - Enhanced activation of RVLM-projecting PVN neurons in rats with chronic heart failure. AB - Previous studies have indicated that there is increased activation of the paraventricular nucleus (PVN) in rats with chronic heart failure (CHF); however, it is not clear if the preautonomic neurons within the PVN are specifically overactive. Also, it is not known if these neurons have altered responses to baroreceptor or osmotic challenges. Experiments were conducted in rats with CHF (6-8 wk after coronary artery ligation). Spontaneously active neurons were recorded in the PVN, of which 36% were antidromically activated from the rostral ventrolateral medulla (RVLM). The baseline discharge rate in RVLM-projecting PVN (PVN-RVLM) neurons from CHF rats was significantly greater than in sham-operated (sham) rats (6.0 +/- 0.6 vs. 2.6 +/- 0.3 spikes/s, P < 0.05). Picoinjection of the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5 phosphonovaleric acid significantly decreased the basal discharge of PVN-RVLM neurons by 80% in CHF rats compared with 37% in sham rats. Fifty-two percent of spontaneously active PVN-RVLM neurons responded to changes in the mean arterial pressure (MAP). The changes in discharge rate in PVN-RVLM neurons after a reduction in MAP (+52 +/- 7% vs. +184 +/- 61%) or an increase in MAP (-42 +/- 8% vs. -71 +/- 6%) were significantly attenuated in rats with CHF compared with sham rats. Most PVN-RVLM neurons (63%), including all barosensitive PVN-RVLM neurons, were excited by an internal carotid artery injection of hypertonic NaCl (2.1 osmol/l), whereas a smaller number (7%) were inhibited. The increase in discharge rate in PVN-RVLM neurons to hypertonic stimulation was significantly enhanced in rats with CHF compared with sham rats (134 +/- 15% vs. 92 +/- 13%). Taken together, these data suggest that PVN-RVLM neurons are more active under basal conditions and this overactivation is mediated by an enhanced glutamatergic tone in rats with CHF. Furthermore, this enhanced activation of PVN-RVLM neurons may contribute to the altered responses to baroreceptor and osmotic challenges observed during CHF. PMID- 22307670 TI - Revisiting the ionic mechanisms of early afterdepolarizations in cardiomyocytes: predominant by Ca waves or Ca currents? AB - Early afterdepolarizations (EADs) have been implicated in severe cardiac arrhythmias and sudden cardiac deaths. However, the mechanism(s) for EAD genesis, especially regarding the relative contribution of Ca(2+) wave (CaW) vs. L-type Ca current (I(Ca,L)), still remains controversial. In the present study, we simultaneously recorded action potentials (APs) and intracellular Ca(2+) images in isolated rabbit ventricular myocytes and systematically compared the properties of EADs in the following two pharmacological models: 1) hydrogen peroxide (H(2)O(2); 200 MUM); and 2) isoproterenol (100 nM) and BayK 8644 (50 nM) (Iso + BayK). We assessed the rate dependency of EADs, the temporal relationship between EADs and corresponding CaWs, the distribution of EADs over voltage, and the effects of blockers of I(Ca,L), Na/Ca exchangers, and ryanodine receptors. The most convincing evidence came from the AP-clamp experiment, in which the cell membrane clamp was switched from current clamp to voltage clamp using a normal AP waveform without EAD; CaWs disappeared in the H(2)O(2) model, but persisted in the Iso + BayK model. We postulate that, although CaWs and reactivation of I(Ca,L) may act synergistically in either case, reactivation of I(Ca,L) plays a predominant role in EAD genesis under oxidative stress (H(2)O(2) model), while spontaneous CaWs are a predominant cause for EADs under Ca(2+) overload condition (Iso + BayK model). PMID- 22307671 TI - Increased PAI-1 in females compared with males is protective for abdominal aortic aneurysm formation in a rodent model. AB - The serine proteases, along with their inhibitor plasmin activator inhibitor-1 (PAI-1), have been shown to play a role in abdominal aortic aneurysm (AAA) formation. The aim of this study is to determine if PAI-1 may be a protective factor for AAA formation and partially responsible for the gender difference observed in AAAs. Male and female wild-type (WT) C57BL/6 and PAI-1(-/-) mice 8-12 wk of age underwent aortic perfusion with porcine pancreatic elastase. Animals were harvested 14 days following perfusion and analyzed for phenotype, PAI-1 protein levels, and matrix metalloproteinase (MMP)-9 and -2 activity. WT males had an average increase in aortic diameter of 80%, whereas females only increased 32% (P < 0.001). PAI-1(-/-) males increased 204% and females 161%, significantly more than their WT counterparts (P < 0.001). Western blot revealed 61% higher PAI 1 protein levels in the WT females compared with the WT males (P = 0.01). Zymography revealed higher levels of pro-MMP-2 and active MMP-2 in the PAI-1(-/-) males and females compared with their WT counterparts. PAI-1(-/-) females had significantly higher serum plasmin levels compared with WT females (P = 0.003). In conclusion, WT female mice are protected from aneurysm formation and have higher levels of PAI-1 compared with males during experimental aneurysm formation. Additionally, both male and female PAI-1(-/-) animals develop significantly larger aneurysms than WT animals, correlating with higher pro- and active MMP-2 levels. These findings suggest that PAI-1 is protective for aneurysm formation in the elastase model of AAA and plays a role in the gender differences seen in AAA formation. PMID- 22307672 TI - Cardiomyocyte overexpression of the alpha1A-adrenergic receptor in the rat phenocopies second but not first window preconditioning. AB - We examined alpha(1A)-adrenergic receptor (AR) mediation of preconditioning in a novel alpha(1A)-AR cardiac transgenic (TG) rat model (alpha(1A)-TG). Compared with nontransgenic littermates (NTLs), in conscious alpha(1A)-TG rats, heart rate was reduced, contractility [left ventricle (LV) +dP/dt, ejection fraction, end systolic elastance] was significantly enhanced, and triple product (LV systolic wall stress * LV +dP/dt * heart rate) was unchanged. However, infarct size (IS)/area at risk (AAR) in response to ischemia-reperfusion (30 min coronary occlusion/3 h reperfusion) was reduced to 35 +/- 4.6% in alpha(1A)-TGs vs. 52 +/- 2.2% in NTLs (P < 0.05). Second window preconditioning reduced IS/AAR in NTLs to 29 +/- 2.7% but did not afford further protection in alpha(1A)-TGs. In contrast, with first window preconditioning, IS/AAR was reduced to similar levels in both alpha(1A)-TGs (12 +/- 1.4%) and NTLs (10 +/- 1.1%). In untreated alpha(1A)-TGs, cardioprotection was associated with enhanced myocardial phosphorylated (p) mitogen/extracellular signal-regulated kinase (MEK), p-extracellular signal regulated kinase (ERK), and inducible nitric oxide synthase (iNOS) at the protein level, along with a 1.3-fold increase in total nitric oxide synthase activity like in second window preconditioning. Affymetrix microarrays revealed that few genes (4.6% of 3,172 upregulated; 8.8% of 3,498 downregulated) showed directionally similar changes in alpha(1A)-TGs vs. NTLs subjected to second window preconditioning. Thus, second, but not first, window cardioprotection is evident in alpha(1A)-TGs in the absence of ischemic preconditioning and is mediated by iNOS activation associated with MEK/ERK phosphorylation. Transcriptionally, however, second window preconditioning is considerably more complex than alpha(1A)-TG preconditioning, with the alteration of thousands of additional genes affording no further protection than that already available in alpha(1A)-TG rats. PMID- 22307673 TI - Cytochrome P-450 2C9 exerts a vasoconstrictor influence on coronary resistance vessels in swine at rest and during exercise. AB - A significant endothelium-dependent vasodilation persists after inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) in the coronary vasculature, which has been linked to the activation of cytochrome P-450 (CYP) epoxygenases expressed in endothelial cells and subsequent generation of vasodilator epoxyeicosatrienoic acids. Here, we investigated the contribution of CYP 2C9 metabolites to regulation of porcine coronary vasomotor tone in vivo and in vitro. Twenty-six swine were chronically instrumented. Inhibition of CYP 2C9 with sulfaphenazole (5 mg/kg iv) alone had no effect on bradykinin-induced endothelium dependent coronary vasodilation in vivo but slightly attenuated bradykinin induced vasodilation in the presence of combined NOS/COX blockade with N(omega) nitro-L-arginine (20 mg/kg iv) and indomethacin (10 mg/kg iv). Sulfaphenazole had minimal effects on coronary resistance vessel tone at rest or during exercise. Surprisingly, in the presence of combined NOS/COX blockade, a significant coronary vasodilator response to sulfaphenzole became apparent, both at rest and during exercise. Subsequently, we investigated in isolated porcine coronary small arteries (~250 MUm) the possible involvement of reactive oxygen species (ROS) in the paradoxical vasoconstrictor influence of CYP 2C9 activity. The vasodilation by bradykinin in vitro in the presence of NOS/COX blockade was markedly potentiated by sulfaphenazole under control conditions but not in the presence of the ROS scavenger N-(2-mercaptoproprionyl)-glycine. In conclusion, CYP 2C9 can produce both vasoconstrictor and vasodilator metabolites. Production of these metabolites is enhanced by combined NOS/COX blockade and is critically dependent on the experimental conditions. Thus production of vasoconstrictors slightly outweighed the production of vasodilators at rest and during exercise. Pharmacological stimulation with bradykinin resulted in vasodilator CYP 2C9 metabolite production when administered in vivo, whereas vasoconstrictor CYP 2C9 metabolites, most likely ROS, were dominant when administered in vitro. PMID- 22307674 TI - Chronic receptor-mediated activation of Gi/o proteins alters basal t-tubular and sarcolemmal L-type Ca2+ channel activity through phosphatases in heart failure. AB - L-type Ca(2+) channels (LTCCs) play an essential role in the excitation contraction coupling of ventricular myocytes. We previously found that t-tubular (TT) LTCC current density was halved by the activation of protein phosphatase (PP)1 and/or PP2A, whereas surface sarcolemmal (SS) LTCC current density was increased by the inhibition of PP1 and/or PP2A activity in failing ventricular myocytes of mice chronically treated with isoproterenol (ISO mice). In the present study, we examined the possible involvement of inhibitory heterotrimeric G proteins (G(i/o)) in these abnormalities by chronically administrating pertussis toxin (PTX) to ISO mice (ISO + PTX mice). Compared with ISO mice, ISO + PTX mice exhibited significantly higher fractional shortening of the left ventricle. The expression level of Galpha(i2) proteins was not altered by the treatment of mice with ISO and/or PTX. ISO + PTX myocytes had normal TT and SS LTCC current densities because they had higher and lower availability and/or open probability of TT and SS LTCCs than ISO myocytes, respectively. A selective PKA inhibitor, H-89, did not affect LTCC current densities in ISO + PTX myocytes. A selective PP2A inhibitor, fostriecin, did not affect SS or TT current density in control or ISO + PTX myocytes but significantly increased TT but not SS LTCC current density in ISO myocytes. These results indicate that chronic receptor mediated activation of G(i/o) in vivo decreases basal TT LTCC activity by activating PP2A and increases basal SS LTCC activity by inhibiting PP1 without modulating PKA in heart failure. PMID- 22307675 TI - Vena cava and aortic smooth muscle cells express transglutaminases 1 and 4 in addition to transglutaminase 2. AB - Transglutaminase (TG) function facilitates several vascular processes and diseases. Although many of these TG-dependent vascular processes have been ascribed to the function of TG2, TG2 knockout mice have a mild vascular phenotype. We hypothesized that TGs besides TG2 exist and function in the vasculature. Biotin-pentylamide incorporation, a measure of general TG activity, was similar in wild-type and TG2 knockout mouse aortae, and the general TG inhibitor cystamine reduced biotin-pentylamine incorporation to a greater extent than the TG2-specific inhibitor Z-DON, indicating the presence of other functional TGs. Additionally, 5-hydroxytryptamine-induced aortic contraction, a TG-activity-dependent process, was decreased to a greater extent by general TG inhibitors vs. Z-DON (maximum contraction: cystamine = abolished, monodansylcadaverine = 28.6 +/- 14.9%, and Z-DON = 60.2 +/- 15.2% vehicle), providing evidence for the importance of TG2-independent activity in the vasculature. TG1, TG2, TG4, and Factor XIII (FXIII) mRNA in rat aortae and vena cavae was detected by RT-PCR. Western analysis detected TG1 and TG4, but not FXIII, in rat aortae and vena cavae and in TG2 knockout and wild-type mouse aortae. Immunostaining confirmed the presence of TG1, TG2, and TG4 in rat aortae and vena cavae, notably in smooth muscle cells; FXIII was absent. K5 and T26, FITC-labeled peptide substrates specific for active TG1 and TG2, respectively, were incorporated into rat aortae and vena cavae and wild-type, but not TG2 knockout, mouse aortae. These studies demonstrate that TG2-independent TG activity exists in the vasculature and that TG1 and TG4 are expressed in vascular tissues. PMID- 22307676 TI - Bariatric surgery to unload the stressed heart: a metabolic hypothesis. AB - Obesity is an independent risk factor for cardiovascular disease. Data from the Framingham Study have reported a higher incidence of heart failure in obese individuals compared with a normal cohort. The body initially copes with the abundance of fuel present in an obese milieu by storing it in adipose tissue. However, when the storage capacity is exceeded, the excess energy is taken up and stored ectopically as fat in vital organs such as the heart. Indeed, intramyocardial lipid overload is present in hearts of obese patients, as well as in hearts of animal models of obesity, and is associated with a distinct gene expression profile and cardiac dysfunction. By imposing a metabolic stress on the heart, obesity causes it to hypertrophy and ultimately to fail. Conventional measures to treat obesity include diet, exercise, and drugs. More recently, weight loss surgery (WLS) has achieved increasing prominence because of its ability to reduce the neurohumoral load, normalize metabolic dysregulation, and improve overall survival. The effects of WLS on systemic metabolic, neurohumoral, and hemodynamic parameters are well described and include an early normalization of serum glucose and insulin levels as well as reduction in blood pressure. WLS is also associated with reverse cardiac remodeling, regression of left ventricular hypertrophy, and improved left ventricular and right ventricular function. By targeting the source of the excess energy, we hypothesize that WLS improves contractile function by limiting exogenous substrate availability to the metabolically overloaded heart. These changes have also been found to be associated with increased levels of adiponectin and improved insulin sensitivity. Taken together, the sustained beneficial effects of WLS on left ventricular mass and function highlight the need to better understand the mechanism by which obesity regulates cardiovascular physiology. PMID- 22307677 TI - 11,12,20-Trihydroxy-eicosa-8(Z)-enoic acid: a selective inhibitor of 11,12-EET induced relaxations of bovine coronary and rat mesenteric arteries. AB - Arachidonic acid is metabolized to four regioisomeric epoxyeicosatrienoic acids (EETs) by cytochrome P-450. 5,6-, 8,9-, 11,12-, and 14,15-EET are equipotent in relaxing bovine coronary arteries (BCAs). Vasorelaxant effects of EETs are nonselectively antagonized by 14,15-epoxyeicosa-5(Z)-enoic acid. The 11,12-EET analogs, 20-hydroxy-11,12-epoxyeicosa-8(Z)-enoic acid (20-H-11,12-EE8ZE) and 11,12,20-trihydroxyeicosa-8(Z)-enoic acid (11,12,20-THE8ZE) were synthesized and tested for antagonist activity against EET-induced relaxations in BCAs. In U 46619-preconstricted arterial rings, 5,6-, 8,9-, 11,12-, and 14,15-EET caused concentration-dependent relaxations with maximal relaxations ranging from 80 to 96%. Preincubation of arteries with 20-H-11,12-EE8ZE (10(-5) M) inhibited relaxations to 14,15- and 11,12-EET, but not 5,6- and 8,9-EET; however, greatest inhibitory effect was against 11,12-EET (maximal relaxation = 80.6 +/- 4.6 vs. 26.7 +/- 7.4% without and with 20-H-11,12-EE8ZE, respectively). Preincubation with the soluble epoxide hydrolase inhibitor (tAUCB, 10(-6) M) significantly enhanced the antagonist effect of 20-H-11,12-EE8ZE against 14,15-EET-induced relaxations (maximal relaxation = 86.6 +/- 4.4 vs. 27.8 +/- 3.3%, without and with 20-H-11,12-EE8ZE and tAUCB) without any change in its effect against 11,12 EET-induced relaxations. In contrast to the parent compound, the metabolite, 11,12,20-THE8ZE (10(-5) M), significantly inhibited relaxations to 11,12-EET and was without effect on other EET regioisomers. Mass spectrometric analysis revealed conversion of 20-H-11,12-EE8ZE to 11,12,20-THE8ZE by incubation with BCA. The conversion was blocked by tAUCB. 14,15-Dihydroxy-eicosa-5Z-enoic acid (a 14,15-EET antagonist), but not 11,12,20-THE8ZE (an 11,12-EET antagonist), inhibited BCA relaxations to arachidonic acid and flow-induced dilation in rat mesenteric arteries. These results indicate that 11,12,20-THE8ZE is a selective antagonist of 11,12-EET relaxations and a useful pharmacological tool to elucidate the function of 11,12-EET in the cardiovascular system. PMID- 22307678 TI - A GmAOX2b antisense gene compromises vegetative growth and seed production in soybean. AB - The alternative oxidase mediates the cyanide-resistant respiratory pathway in plant mitochondria. In non-thermogenic plants, the role of alternative oxidase in plant growth and development is not well understood. Soybean (Glycine max) lines carrying a GmAOX2b antisense gene had compromised vegetative growth and reproductive performance under typical glasshouse growth conditions. The reduction in vegetative growth was demonstrated by reduction in shoot height, the number of leaves per plant and the green leaf area. Antisense plants also had decreased pod formation and seed to pod ratios, which together led to a reduction in the number and total mass of seed produced. The negative effects of the antisense gene on pod set, seed set, ovule availability and total seed mass were primarily confined to the branches, rather than the main stem. The preferential effect of alternative oxidase suppression in the branches is discussed in relation to the reproductive potential of soybean under stress. Taken together, these results demonstrate that alternative oxidase provides the benefit of sustaining plant vegetative growth and reproductive capacity in soybean. PMID- 22307679 TI - Genetic screens for the control of influenza virus replication: from meta analysis to drug discovery. AB - Current anti-influenza virus drugs target two viral proteins and induce a selective pressure for the generation of drug resistant variants. This stresses the need for additional therapeutic strategies including drug targeting of cellular factors that are essential for viral replication. Reverse genetics approaches can be used to identify these factors and recently six independent genomic initiatives have led to the identification of 925 host factors that are essential for the replication of influenza viruses. Here we report a meta analysis of this dataset, first revealing that these screens are poorly overlapping at the gene level. However, a strong convergence was observed at the level of biological processes which was further supported by an interactomic analysis showing a high interconnectivity of the essential host factors in the human protein network. Plugging virus-host protein interaction data on this dataset reveals a significant targeting of these factors by viral proteins, further validating the cellular targets. Combining this information, the first drug-influenza virus target network was constructed by retrieving from DrugBank 298 molecules interacting with 100 essential host factors. Of these, 204 are FDA approved offering interesting potential for rapid drug repositioning in the treatment of flu. PMID- 22307680 TI - The amyloid-beta isoform pattern in cerebrospinal fluid in familial PSEN1 M139T- and L286P-associated Alzheimer's disease. AB - There are several familial forms of Alzheimer's disease (AD) most of which are caused by mutations in the genes that encode the presenilin enzymes involved in the production of amyloid-beta (Abeta) from the amyloid precursor protein (APP). In AD, Abeta forms fibrils that are deposited in the brain as plaques. Much of the fibrillar Abeta found in the plaques consists of the 42 amino acid form of Abeta (Abeta1-42) and it is now widely accepted that Abeta is related to the pathogenesis of AD and that Abeta may both impair memory and be neurotoxic. In human cerebrospinal fluid (CSF) several C- and N-terminally truncated Abeta isoforms have been detected and their relative abundance pattern is thought to reflect the production and clearance of Abeta. By using immunoprecipitation and mass spectrometry, we have previously demonstrated that carriers of the familial AD (FAD)-associated PSEN1 A431E mutation have low CSF levels of C-terminally truncated Abeta isoforms shorter than Abeta1-40. Here we replicate this finding in symptomatic carriers of the FAD-causing PSEN1 L286P mutation. Furthermore, we show that preclinical carriers of the PSEN1 M139T mutation may overexpress Abeta1 42 suggesting that this particular mutation may cause AD by stimulating gamma secretase-mediated cleavage at amino acid 42 in the Abeta sequence. PMID- 22307681 TI - Computational hemodynamic optimization predicts dominant aortic arch selection is driven by embryonic outflow tract orientation in the chick embryo. AB - In the early embryo, a series of symmetric, paired vessels, the aortic arches, surround the foregut and distribute cardiac output to the growing embryo and fetus. During embryonic development, the arch vessels undergo large-scale asymmetric morphogenesis to form species-specific adult great vessel patterns. These transformations occur within a dynamic biomechanical environment, which can play an important role in the development of normal arch configurations or the aberrant arch morphologies associated with congenital cardiac defects. Arrested migration and rotation of the embryonic outflow tract during late stages of cardiac looping has been shown to produce both outflow tract and several arch abnormalities. Here, we investigate how changes in flow distribution due to a perturbation in the angular orientation of the embryonic outflow tract impact the morphogenesis and growth of the aortic arches. Using a combination of in vivo arch morphometry with fluorescent dye injection and hemodynamics-driven bioengineering optimization-based vascular growth modeling, we demonstrate that outflow tract orientation significantly changes during development and that the associated changes in hemodynamic load can dramatically influence downstream aortic arch patterning. Optimization reveals that balancing energy expenditure with diffusive capacity leads to multiple arch vessel patterns as seen in the embryo, while minimizing energy alone led to the single arch configuration seen in the mature arch of aorta. Our model further shows the critical importance of the orientation of the outflow tract in dictating morphogenesis to the adult single arch and accurately predicts arch IV as the dominant mature arch of aorta. These results support the hypothesis that abnormal positioning of the outflow tract during early cardiac morphogenesis may lead to congenital defects of the great vessels due to altered hemodynamic loading. PMID- 22307682 TI - A power-law rheology-based finite element model for single cell deformation. AB - Physical forces can elicit complex time- and space-dependent deformations in living cells. These deformations at the subcellular level are difficult to measure but can be estimated using computational approaches such as finite element (FE) simulation. Existing FE models predominantly treat cells as spring dashpot viscoelastic materials, while broad experimental data are now lending support to the power-law rheology (PLR) model. Here, we developed a large deformation FE model that incorporated PLR and experimentally verified this model by performing micropipette aspiration on fibroblasts under various mechanical loadings. With a single set of rheological properties, this model recapitulated the diverse micropipette aspiration data obtained using three protocols and with a range of micropipette sizes. More intriguingly, our analysis revealed that decreased pipette size leads to increased pressure gradient, potentially explaining our previous counterintuitive finding that decreased pipette size leads to increased incidence of cell blebbing and injury. Taken together, our work leads to more accurate rheological interpretation of micropipette aspiration experiments than previous models and suggests pressure gradient as a potential determinant of cell injury. PMID- 22307683 TI - Calcific nodule morphogenesis by heart valve interstitial cells is strain dependent. AB - Calcific aortic valve disease (CAVD) results in impaired function through the inability of valves to fully open and close, but the causes of this pathology are unknown. Stiffening of the aorta is associated with CAVD and results in exposing the aortic valves to greater mechanical strain. Transforming growth factor beta1 (TGF-beta1) is enriched in diseased valves and has been shown to combine with strain to synergistically alter aortic valve interstitial cell (AVIC) phenotypes. Therefore, we investigated the role of strain and TGF-beta1 on the calcification of AVICs. Following TGF-beta1 pretreatment, strain induced intact monolayers to aggregate and calcify. Using a wound assay, we confirmed that TGF-beta1 increases tension in the monolayer in parallel with alpha-smooth muscle actin (alphaSMA) expression. Continual exposure to strain accelerates aggregates to calcify into mature nodules that contain a necrotic core surrounded by an apoptotic ring. This phenotype appears to be mediated by strain inhibition of AVIC migration after the initial formation of aggregates. To better interpret the extent to which externally applied strain physically impacts this process, we modified the classical Lame solution, derived using principles from linear elasticity, to reveal strain magnification as a novel feature occurring in a mechanical environment that supports nodule formation. These results indicate that strain can impact multiple points of nodule formation: by modifying tension in the monolayer, remodeling cell contacts, migration, apoptosis, and mineralization. Therefore, strain-induced nodule formation provides new directions for developing strategies to address CAVD. PMID- 22307684 TI - Preparation of polymer decorated graphene oxide by gamma-ray induced graft polymerization. AB - Herein, we report a facile approach to decorate graphene oxide (GO) sheets with poly(vinyl acetate) (PVAc) by gamma-ray irradiation-induced graft polymerization. The content of PVAc in the obtained sample, i.e., PVAc grafted GO (GO-g-PVAc) is calculated by the loss weight in thermogravimetric analysis (TGA) curves. A GO-g PVAc sample with a degree of grafting (DG) of 28.5% was well dispersed in common organic solvents and the dispersions obtained were extremely stable at room temperature without any aggregation, even after standing for 2 months. The excellent dispersibility and stability of GO-g-PVAc in common organic solvents are readily rationalized in terms of the full coverage of PVAc chains and solvated layer formation on graphene oxide sheets surface, which weakens the interlaminar attraction of GO sheets. This approach presents a facile route for the preparation of dispersible GO and shows great potential in the preparation of graphene-based composites by solution-processes. PMID- 22307685 TI - Clinical images: Eagle's syndrome. PMID- 22307686 TI - Deploying insulin granule-granule fusion to rescue deficient insulin secretion in diabetes. AB - According to our current understanding of insulin exocytosis, insulin granules dock on the plasma membrane, undergo priming and then wait for calcium-triggered fusion. In this issue of Diabetologia, Hoppa et al (doi 10.1007/s00125-011-2400-5 ) report that cholinergic stimulation induces granule-granule, or multivesicular, fusion to effect more efficient insulin release. Other exocytotic modes of insulin secretion, particularly those induced by incretin stimulation, include orderly granule fusion with granules already fused with the plasma membrane, called sequential exocytosis, and recruitment of newcomer granules to fuse with plasma membrane with minimal time for docking and priming. The molecular machineries that mediate these distinct exocytotic modes of granule-granule fusion and newcomer granules remain undefined, but they could be therapeutically targeted to couple to cholinergic and incretin stimulation to rescue the deficient glucose-stimulated insulin secretion in diabetes. PMID- 22307687 TI - Clinical and molecular analysis of a Chinese family with autosomal dominant neurohypophyseal diabetes insipidus associated with a novel missense mutation in the vasopressin-neurophysin II gene. AB - The objective of this study is to identify the genetic defects in a Chinese family with autosomal dominant familial neurohypophyseal diabetes insipidus. Complete physical examination, fluid deprivation, and DDAVP tests were performed in three affected and three healthy members of the family. Genomic DNA was extracted from leukocytes of venous blood of these individuals for polymerase chain reaction amplification and direct sequencing of all three coding exons of arginine vasopressin-neurophysin II (AVP-NPII) gene. Seven members of this family were suspected to have symptomatic vasopressin-deficient diabetes insipidus. The water deprivation test in all the patients confirmed the diagnosis of vasopressin deficient diabetes insipidus, with the pedigree demonstrating an autosomal dominant inheritance. Direct sequence analysis revealed a novel mutation (c.193T>A) and a synonymous mutation (c.192C>A) in the AVP-NPII gene. The missense mutation resulted in the substitution of cysteine by serine at a highly conserved codon 65 of exon 2 of the AVP-NPII gene in all affected individuals, but not in unaffected members. We concluded that a novel missense mutation in the AVP-NPII gene caused neurohypophyseal diabetes insipidus in this family, due to impaired neurophysin function as a carrier protein for AVP. The Cys65 is essential for NPII in the formation of a salt bridge with AVP. Presence of this mutation suggests that the portion of the neurophysin peptide encoded by this sequence is important for the normal expression of vasopressin. PMID- 22307688 TI - The relationships between snail1 and estrogen receptor signaling in breast cancer cells. AB - The loss of hormonal dependency of breast tumor cells is often accompanied with the appearance of epithelial-mesenchymal transition (EMT) features and increase in cell metastasis and invasiveness. The central role in the EMT belongs to transcription factors Snail responded for the decrease in E-cadherin expression and cell contacts, stimulation of cell mobility and invasiveness. Aim was to study the relationships between estrogen receptor machinery and Snail1 signaling, and mechanism of Snail1 regulation in hormone-resistant breast cancer cells. The experiments were performed on the estrogen-dependent MCF-7 breast cancer cells, estrogen-hyposensitive MCF-7/LS subline generated through long-term cultivation of the parental cells in steroid-free medium, and ER-negative estrogen-resistant HBL-100 cells. Snail1, estrogen receptor, p65 NF-kappaB, E-cadherin levels were analyzed by Western blot. We found that decrease in the estrogen dependency is correlated with increase in Snail1 expression and activity, we demonstrated the Snail1 involvement in the negative regulation of ER, and showed that Snail1 inhibition partially restores the sensitivity of the estrogen-hyposensitive cells to antiestrogen tamoxifen. Furthermore, NF-kappaB was found to serve as a positive regulator of Snail1 in breast cancer cells, and simultaneous inhibition of NF-kappaB and Snail1 resulted in additional increase in cell response to tamoxifen. In general, the results obtained demonstrate the phenomenon of Snail1 activation in the hormone-resistant breast cancer cells, and show that Snail1 and NF-kappaB may serve as an important targets in the treatment of breast cancer, both estrogen-dependent and estrogen-independent tumors. PMID- 22307689 TI - MDCT of abdominal wall lumbar hernias: anatomical review, pathologic findings and differential diagnosis. AB - PURPOSE: To review the anatomical landmarks of the abdominal wall lumbar region and its normal appearance on multidetector computed tomography (MDCT) and to briefly describe the MDCT features of lumbar hernias. METHODS: We performed a retrospective search of the imaging report database from November 2007 to October 2011. We retrieved the clinical data and MDCT studies of patients suffering from abdominal wall lumbar hernias. We reviewed the imaging features of abdominal lumbar hernias and compared those with the normal appearance of the lumbar region in asymptomatic individuals. RESULTS: We classified lumbar wall hernias as diffuse, superior (or Grynfelt-Lesshaft) and inferior (or Petit) lumbar hernias. We briefly describe the imaging features of each subtype and review the anatomy and MDCT appearance of normal lumbar region. CONCLUSIONS: Currently available MDCT provides an excellent opportunity for reviewing the normal anatomy of the wall lumbar region and may be considered a useful modality for evaluating lumbar hernias. PMID- 22307690 TI - Genetic terminology. AB - Common terms used in genetics with multiple meanings are explained and the terminology used in subsequent chapters is defined. Statistical Human Genetics has existed as a discipline for over a century, and during that time the meanings of many of the terms used have evolved, largely driven by molecular discoveries, to the point that molecular and statistical geneticists often have difficulty understanding each other. It is, therefore, imperative, now that so much of molecular genetics is becoming an in silico statistical science, that we have well-defined, common terminology. PMID- 22307691 TI - Identification of genotype errors. AB - It has been documented that there exist some errors in most large genotype datasets and that an error rate of 1-2% is adequate to lead to the distortion of map distance as well as a false conclusion of linkage (Abecasis et al. Eur J Hum Genet 9(2):130-134, 2001), therefore one needs to ensure that the data are as clean as possible. On the other hand, the process of data cleaning is tedious and demands efforts and experience. O'Connell and Weeks implemented four error checking algorithms in computer software called PedCheck. In this chapter, the four algorithms implemented in PedCheck are discussed with a focus on the genotype-elimination method. Furthermore, an example for four levels of error checking permitted by PedCheck is provided with the required input files. In addition, alternative algorithms implemented in other statistical computing programs are also briefly discussed. PMID- 22307692 TI - Detecting pedigree relationship errors. AB - Pedigree relationship errors often occur in family data collected for genetic studies, and unidentified errors can lead to either increased false positives or decreased power in both linkage and association analyses. Here we review several allele sharing, as well as likelihood-based statistics, that were proposed to efficiently extract genealogical information from available genome-wide marker data, and the software package PREST that implements these methods. We provide detailed analytical steps involved using two application examples, and we discuss various practical issues including results interpretation. PMID- 22307693 TI - Identifying cryptic relationships. AB - Cryptic relationships such as first-degree relatives often appear in studies that collect population samples such as the case-control genome-wide association studies (GWAS). Cryptic relatedness not only creates increased type 1 error rate but also affects other aspects of GWAS, such as population stratification via principal component analysis. Here we discuss two effective methods, as implemented in PREST and PLINK, to detect and correct for the problem of cryptic relatedness using high-throughput SNP data collected from GWAS or next-generation sequencing (NGS) experiments. We provide the analytical and practical details involved using three application examples. PMID- 22307694 TI - Estimating allele frequencies. AB - Methods of estimating allele frequencies from data on unrelated and related individuals are described in this chapter. For samples of unrelated individuals with simple codominant markers, the natural estimator of allele frequencies can be used. For genetic data on related individuals, maximum likelihood estimation (MLE) can be applied to compute allele frequencies. Factors that influence allele frequencies in populations are also explained. PMID- 22307695 TI - Testing departure from Hardy-Weinberg proportions. AB - The Hardy-Weinberg principle, one of the most important principles in population genetics, was originally developed for the study of allele frequency changes in a population over generations. It is now, however, widely used in studies of human diseases to detect inbreeding, populations stratification, and genotyping errors. For assessment of deviation from the Hardy-Weinberg proportions in data, the most popular approaches include the asymptotic Pearson's chi-square goodness-of-fit test and the exact test. The Pearson's chi-square goodness-of-fit test is simple and straightforward, but it is very sensitive to small sample size or rare allele frequency. The exact test of Hardy-Weinberg proportions is preferable in these situations. The exact test can be performed through complete enumeration of heterozygote genotypes or on the basis of the Markov chain Monte Carlo procedure. In this chapter, we describe the Hardy-Weinberg principle and the commonly used Hardy-Weinberg proportions tests and their applications, and we demonstrate how the chi-square test and exact test of Hardy-Weinberg proportions can be performed step-by-step using the popular software programs SAS, R, and PLINK, which have been widely used in genetic association studies, along with numerical examples. We also discuss recent approaches for testing Hardy-Weinberg proportions in case control study designs that are better than traditional approaches for testing Hardy-Weinberg proportions in controls only. Finally, we note that deviation from the Hardy-Weinberg proportions in affected individuals can provide evidence for an association between genetic variants and diseases. PMID- 22307696 TI - Estimating disequilibrium coefficients. AB - Gametic phase disequilibrium (GPD) is the nonrandom association of alleles within gametes. Linkage disequilibrium (LD) describes the special case of deviation from independence between alleles at two linked genetic loci. Estimation of allelic LD requires knowledge of haplotypes. Genotype-based LD measures dispense with the haplotype estimation step and avoid bias in LD estimation. In this chapter, the most important measures for allelic and genotypic LD are introduced. The use of software packages for LD estimation is illustrated. PMID- 22307697 TI - Detecting familial aggregation. AB - Beyond calculating parameter estimates to characterize the distribution of genetic features of populations (frequencies of mutations in various regions of the genome, allele frequencies, measures of Hardy-Weinberg disequilibrium), genetic epidemiology aims to identify correlations between genetic variants and phenotypic traits, with considerable emphasis placed on finding genetic variants that increase susceptibility to disease and disease-related traits. However, determining correlation alone does not suffice: genetic variants common in an isolated ethnic group with a high burden of a given disease may show relatively high correlation with disease but, as markers of ethnicity, these may not necessarily have any functional role in disease. To establish a causal relationship between genetic variants and disease (or disease-related traits), proper statistical analyses of human data must incorporate epidemiologic approaches to examining sets of families or unrelated individuals with information available on individuals' disease status or related traits.Through different analytical approaches, statistical analysis of human data can answer several important questions about the relationship between genes and disease: 1. Does the disease tend to cluster in families more than expected by chance alone? 2. Does the disease appear to follow a particular genetic model of transmission in families? 3. Do variants at a particular genetic marker tend to cosegregate with disease in families? 4. Do specific genetic markers tend to be carried more frequently by those with disease than by those without, in a given population (or across families)? The first question can be examined using studies of familial aggregation or correlation. An ancillary question: "how much of the susceptibility to disease (or variation in disease-related traits) might be accounted for by genetic factors?" is typically answered by estimating heritability, the proportion of disease susceptibility or trait variation attributable to genetics. The second question can be formally tested using pedigrees for which disease affection status or trait values are available through a modeling approach known as segregation analysis. The third question can be answered with data on pedigrees with affected members and genotype information at markers of interest, using linkage analysis. The fourth question is answerable using genotype information at markers on unrelated affected and unaffected individuals and/or families with affected and unaffected members. All of these questions can also be explored for quantitative (or continuously distributed) traits by examining variation in trait values between family members or between unrelated individuals. While each of these questions and the analytical approaches for answering them is explored extensively in subsequent chapters (heritability in Chapters 9 and 10, segregation in Chapter 12, linkage in Chapters 13-17, and association in Chapters 18-21 and 23), this chapter focuses on statistical methods to answer questions of familial aggregation. PMID- 22307698 TI - Estimating heritability from twin studies. AB - This chapter describes how the heritability of a trait can be estimated using data collected from pairs of twins. The principles of the classical twin design are described, followed by the assumptions and possible extensions of the design. In the second part of this chapter, two example scripts are presented and described, explaining the basic steps for estimating heritability using the statistical program OpenMx. OpenMx and the scripts used for this chapter can be downloaded so that readers can adapt and use the scripts for their own purposes. PMID- 22307699 TI - Estimating heritability from nuclear family and pedigree data. AB - Heritability is a measure of familial resemblance. Estimating the heritability of a trait represents one of the first steps in the gene mapping process. This chapter describes how to estimate heritability for quantitative traits from nuclear and pedigree data using the ASSOC program in the Statistical Analysis for Genetic Epidemiology (S.A.G.E.) software package. Estimating heritability rests on the assumption that the total phenotypic variance of a quantitative trait can be partitioned into independent genetic and environmental components. In turn, the genetic variance can be divided into an additive (polygenic) genetic variance, a dominance variance (nonlinear interaction effects between alleles at the same locus), and an epistatic variance (interaction effects between alleles at different loci). The last two are often assumed to be zero. The additive genetic variance represents the average effects of individual alleles on the phenotype and reflects transmissible resemblance between relatives. Heritability in the narrow sense (h (2)) refers to the ratio of the additive genetic variance to the total phenotypic variance. Heritability is a dimensionless population specific parameter. ASSOC estimates association parameters (regression coefficients) and variance components from family data. ASSOC uses a linear regression model in which the total residual variance is partitioned, after regressing on covariates, into the sum of a random additive polygenic component, a random sibship component, random nuclear family components, a random marital component, and an individual-specific random component. Assortative mating, nonrandom ascertainment of families and failure to account for key confounding factors may bias heritability estimates. PMID- 22307700 TI - Correcting for ascertainment. AB - Data used to study human genetics are often not obtained by simple random sampling, which is assumed by many statistical methods, especially those that are based on likelihood for making inferences. There is a well-developed theory to correct likelihoods based on sibship data whether or not the exact mode of ascertainment is known. In the case of larger pedigrees, however, the problem is much more difficult unless they are recruited into the sample by single ascertainment. There is no one piece of software that analyzes ascertainment in general, so most of this chapter is devoted to theory. A general method by which one general genetic analysis software package corrects pedigree data for ascertainment is briefly described. PMID- 22307701 TI - Segregation analysis using the unified model. AB - Segregation analysis is a basic tool in human genetics. It is a statistical method to determine if a trait, continuous or binary, has a transmission pattern in pedigrees that is consistent with Mendelian segregation. Major locus segregation is combined together with multifactorial/polygenic inheritance in the unified model. Segregation analysis as a procedure to identify the presence of segregation at a major Mendelian locus, with/without multifactorial inheritance, is introduced in this chapter. It is illustrated with the program SEGREG in the Statistical Analysis for Genetic Epidemiology (S.A.G.E.) package, which can use either regressive models or the finite polygenic mixed model to incorporate the multifactorial/polygenic component. PMID- 22307702 TI - Design considerations for genetic linkage and association studies. AB - This chapter describes the main issues that genetic epidemiologists usually consider in the design of linkage and association studies. For linkage, we briefly consider the situation of rare, highly penetrant alleles showing a disease pattern consistent with Mendelian inheritance investigated through parametric methods in large pedigrees or with autozygosity mapping in inbred families, and we then turn our focus to the most common design, affected sibling pairs, of more relevance for common, complex diseases. Theoretical and more practical power and sample size calculations are provided as a function of the strength of the genetic effect being investigated. We also discuss the impact of other determinants of statistical power such as disease heterogeneity, pedigree, and genotyping errors, as well as the effect of the type and density of genetic markers. Linkage studies should be as large as possible to have sufficient power in relation to the expected genetic effect size. Segregation analysis, a formal statistical technique to describe the underlying genetic susceptibility, may assist in the estimation of the relevant parameters to apply, for instance. However, segregation analyses estimate the total genetic component rather than a single-locus effect. Locus heterogeneity should be considered when power is estimated and at the analysis stage, i.e. assuming smaller locus effect than the total the genetic component from segregation studies. Disease heterogeneity should be minimised by considering subtypes if they are well defined or by otherwise collecting known sources of heterogeneity and adjusting for them as covariates; the power will depend upon the relationship between the disease subtype and the underlying genotypes. Ultimately, identifying susceptibility alleles of modest effects (e.g. RR<=1.5) requires a number of families that seem unfeasible in a single study. Meta-analysis and data pooling between different research groups can provide a sizeable study, but both approaches require even a higher level of vigilance about locus and disease heterogeneity when data come from different populations. All necessary steps should be taken to minimise pedigree and genotyping errors at the study design stage as they are, for the most part, due to human factors. A two-stage design is more cost-effective than one stage when using short tandem repeats (STRs). However, dense single nucleotide polymorphism (SNP) arrays offer a more robust alternative, and due to their lower cost per unit, the total cost of studies using SNPs may in the future become comparable to that of studies using STRs in one or two stages. For association studies, we consider the popular case-control design for dichotomous phenotypes, and we provide power and sample size calculations for one-stage and multistage designs. For candidate genes, guidelines are given on the prioritisation of genetic variants, and for genome-wide association studies (GWAS), the issue of choosing an appropriate SNP array is discussed. A warning is issued regarding the danger of designing an underpowered replication study following an initial GWAS. The risk of finding spurious association due to population stratification, cryptic relatedness, and differential bias is underlined. GWAS have a high power to detect common variants of high or moderate effect. For weaker effects (e.g. relative risk<1.2), the power is greatly reduced, particularly for recessive loci. While sample sizes of 10,000 or 20,000 cases are not beyond reach for most common diseases, only meta-analyses and data pooling can allow attaining a study size of this magnitude for many other diseases. It is acknowledged that detecting the effects from rare alleles (i.e. frequency<5%) is not feasible in GWAS, and it is expected that novel methods and technology, such as next-generation resequencing, will fill this gap. At the current stage, the choice of which GWAS SNP array to use does not influence the power in populations of European ancestry. A multistage design reduces the study cost but has less power than the standard one-stage design. If one opts for a multistage design, the power can be improved by jointly analysing the data from different stages for the SNPs they share. The estimates of locus contribution to disease risk from genome-wide scans are often biased, and relying on them might result in an underpowered replication study. Population structure has so far caused less spurious associations than initially feared, thanks to systematic ethnicity matching and application of standard quality control measures. Differential bias could be a more serious threat and must be minimised by strictly controlling all the aspects of DNA acquisition, storage, and processing. PMID- 22307703 TI - Model-based linkage analysis of a quantitative trait. AB - Linkage analysis is a family-based method of analysis to examine whether any typed genetic markers co-segregate with a given trait, in this case a quantitative trait. If linkage exists, this is taken as evidence in support of a genetic basis for the trait. Historically, linkage analysis was performed using a binary disease trait, but has been extended to include quantitative disease measures. Quantitative traits are desirable as they provide more information than binary traits. Linkage analysis can be performed using single marker methods (one marker at a time) or multipoint (using multiple markers simultaneously). In model based linkage analysis, the genetic model for the trait of interest is specified. There are many software options for performing linkage analysis. Here, we use the program package Statistical Analysis for Genetic Epidemiology (S.A.G.E.). S.A.G.E. was chosen because it includes programs to perform data cleaning procedures and to generate and test genetic models for a quantitative trait, in addition to performing linkage analysis. We demonstrate in detail the process of running the program LODLINK to perform single marker analysis and MLOD to perform multipoint analysis using output from SEGREG, where SEGREG was used to determine the best fitting statistical model for the trait. PMID- 22307704 TI - Model-based linkage analysis of a binary trait. AB - Linkage analysis is a statistical genetics method to localize disease and trait genes to specific chromosome regions. The analysis requires pedigrees with members who vary among each other in the trait of interest and who have been genotyped with known genetic markers. Linkage analysis tests whether any of the marker alleles cosegregate with the disease or trait within the pedigree. Evidence of cosegregation is then combined across the families. We describe here the background and methods to conduct a linkage analysis for a binary trait, such as a disease, when the model of the gene contributing to the trait can be formulated. There are a number of statistical genetics software packages that allow you conduct a model-based linkage analysis of a binary trait. We describe in great detail how to run one of the programs, the LODLINK program of the Statistical Analysis for Genetic Epidemiology (S.A.G.E.) package. We provide directions for making the four input files and information on how to access and interpret the output files. We then discuss more complex analyses that can be conducted. We discuss the MLOD program for multipoint linkage analysis, including its relation to LODLINK and the additional file needed. Notes to improve your ability to run the program are included. PMID- 22307705 TI - Model-free linkage analysis of a quantitative trait. AB - Model-free methods of linkage analysis for quantitative traits are a class of easily implemented, computationally efficient, and statistically robust approaches to searching for linkage to a quantitative trait. By "model-free" we refer to methods of linkage analysis that do not fully specify a genetic model (i.e., the causal allele frequency and penetrance functions). In this chapter, we briefly survey the methods that are available, and then we discuss the necessary steps to implement an analysis using the programs GENIBD, SIBPAL, and RELPAL in the Statistical Analysis for Genetic Epidemiology (S.A.G.E.) software suite. PMID- 22307706 TI - Model-free linkage analysis of a binary trait. AB - Genetic linkage analysis aims to detect chromosomal regions containing genes that influence risk of specific inherited diseases. The presence of linkage is indicated when a disease or trait cosegregates through the families with genetic markers at a particular region of the genome. Two main types of genetic linkage analysis are in common use, namely model-based linkage analysis and model-free linkage analysis. In this chapter, we focus solely on the latter type and specifically on binary traits or phenotypes, such as the presence or absence of a specific disease. Model-free linkage analysis is based on allele-sharing, where patterns of genetic similarity among affected relatives are compared to chance expectations. Because the model-free methods do not require the specification of the inheritance parameters of a genetic model, they are preferred by many researchers at early stages in the study of a complex disease. We introduce the history of model-free linkage analysis in Subheading 1. Table 1 describes a standard model-free linkage analysis workflow. We describe three popular model free linkage analysis methods, the nonparametric linkage (NPL) statistic, the affected sib-pair (ASP) likelihood ratio test, and a likelihood approach for pedigrees. The theory behind each linkage test is described in this section, together with a simple example of the relevant calculations. Table 4 provides a summary of popular genetic analysis software packages that implement model-free linkage models. In Subheading 2, we work through the methods on a rich example providing sample software code and output. Subheading 3 contains notes with additional details on various topics that may need further consideration during analysis. PMID- 22307707 TI - Single marker association analysis for unrelated samples. AB - Methods for single marker association analysis are presented for binary and quantitative traits. For a binary trait, we focus on the analysis of retrospective case-control data using Pearson's chi-squared test, the trend test, and a robust test. For a continuous trait, typical methods are based on a linear regression model or the analysis of variance. We illustrate how these tests can be applied using a public available R package "Rassoc" and some existing R functions. Guidelines for choosing these test statistics are provided. PMID- 22307708 TI - Single-marker family-based association analysis conditional on parental information. AB - Family-based designs have been commonly used in association studies. Different family structures such as extended pedigrees and nuclear families, including parent-offspring triads and families with multiple affected siblings (multiplex families), can be ascertained for family-based association analysis. Flexible association tests that can accommodate different family structures have been proposed. The pedigree disequilibrium test (PDT) (Am J Hum Genet 67:146-154, 2000) can use full genotype information from general (possibly extended) pedigrees with one or multiple affected siblings but requires parental genotypes or genotypes of unaffected siblings. On the other hand, the association in the presence of linkage (APL) test (Am J Hum Genet 73:1016-1026, 2003) is restricted to nuclear families with one or more affected siblings but can infer missing parental genotypes properly by accounting for identity-by-descent (IBD) parameters. Both the PDT and APL are powerful association tests in the presence of linkage and can be used as complementary tools for association analysis. This chapter introduces these two tests and compares their properties. Recommendations and notes for performing the tests in practice are provided. PMID- 22307709 TI - Single marker family-based association analysis not conditional on parental information. AB - Family-based association analysis unconditional on parental genotypes models the effects of observed genotypes. This approach has been shown to have greater power than conditional methods. In this chapter, I review two popular association analysis methods accounting for familial correlations: the marginal model using generalized estimating equations (GEE) and the mixed model with a polygenic random component. The marginal approach does not explicitly model familial correlations but uses the information to improve the efficiency of parameter estimates. This model, using GEE, is useful when the correlation structure is not of interest; the correlations are treated as nuisance parameters. In the mixed model, familial correlations are modeled as random effects, e.g., the polygenic inheritance model accounts for correlations originating from shared genomic components within a family. These unconditional methods provide a flexible modeling framework for general pedigree data to accommodate traits with various distributions and many types of covariate effects. The analysis procedures are demonstrated using the ASSOC program in the S.A.G.E. package and the R package gee, including how to prepare input data, conduct the analysis, and interpret the output. ASSOC allows models to include random components of additional familial correlations that may be not sufficiently explained by a polygenic effect and addresses nonnormality of response variables by transformation methods. With its ease of use, ASSOC provides a useful tool for association analysis of large pedigree data. PMID- 22307710 TI - Allowing for population stratification in association analysis. AB - In genetic association studies, it is necessary to correct for population structure to avoid inference bias. During the past decade, prevailing corrections often only involved adjustments of global ancestry differences between sampled individuals. Nevertheless, population structure may vary across local genomic regions due to the variability of local ancestries associated with natural selection, migration, or random genetic drift. Adjusting for global ancestry alone may be inadequate when local population structure is an important confounding factor. In contrast, adjusting for local ancestry can more effectively prevent false-positives due to local population structure. To more accurately locate disease genes, we recommend adjusting for local ancestries by interrogating local structure. In practice, locus-specific ancestries are usually unknown and cannot be accurately inferred when ancestral population information is not available. For such scenarios, we propose employing local principal components (PC) to represent local ancestries and adjusting for local PCs when testing for genotype-phenotype association. With an acceptable computation burden, the proposed algorithm successfully eliminates the known spurious association between SNPs in the LCT gene and height due to the population structure in European Americans. PMID- 22307711 TI - Haplotype inference. AB - Haplotypes, as they specify linkage patterns between individual nucleotide variants, confer critical information for understanding the genetics of human diseases. However, haplotype information is not directly obtainable from high throughput genotyping platforms. In this chapter, we introduce two representative methods to reconstruct haplotypes from unphased genotype data, one method is for unrelated individuals and the other is for families. PMID- 22307712 TI - Multi-SNP haplotype analysis methods for association analysis. AB - This chapter reviews the rationale for the use of haplotypes in association-based testing, discusses statistical issues related to haplotype uncertainty that complicate the analysis, then gives practical guidance for testing haplotype based associations with phenotype or outcome trait, first of candidate gene regions and then for the genome as a whole. Haplotypes are interesting for two reasons: First, they may be in closer LD with a causal variant than any single measured SNP, and therefore may enhance the coverage value of the genotypes over single SNP analysis. Second, haplotypes may themselves be the causal variants of interest and some solid examples of this have appeared in the literature. This chapter discusses three possible approaches to incorporation of SNP haplotype analysis into generalized linear regression models: (1) a simple substitution method involving imputed haplotypes; (2) simultaneous maximum likelihood (ML) estimation of all parameters, including haplotype frequencies and regression parameters; and (3) a simplified approximation to full ML for case-control data. Examples of the various approaches for a haplotype analysis of a candidate gene are provided. We compare the behavior of the approximation-based methods and show that in most instances the simpler methods hold up well in practice. We also describe the practical implementation of genome-wide haplotype risk estimation and discuss several shortcuts that can be used to speed up otherwise potentially very intensive computational requirements. PMID- 22307713 TI - Detecting rare variants. AB - The limitations of genome-wide association (GWA) studies that are based on the common disease common variants (CDCV) hypothesis have motivated geneticists to test the hypothesis that rare variants contribute to the variation of common diseases, i.e., common disease/rare variants (CDRV). The newly developed high throughput sequencing technologies have made the studies of rare variants practicable. Statistical approaches to test associations between a phenotype and rare variants are quickly developing. The central idea of these methods is to test a set of rare variants in a defined region or regions by collapsing or aggregating rare variants, thereby improving the statistical power. In this chapter, we introduce these methods as well as their applications in practice. PMID- 22307714 TI - The analysis of ethnic mixtures. AB - Populations of ethnic mixtures can be useful in genetic studies. Admixture mapping, or mapping by admixture linkage disequilibrium (MALD), is specially developed for admixed populations and can supplement traditional genome-wide association analyses in the search for genetic variants underlying complex traits. Admixture mapping tests the association between a trait and locus specific ancestries. The locus-specific ancestries are in linkage disequilibrium (LD) which is generated by the admixture process between genetically distinct ancestral populations. Because of highly correlated locus-specific ancestries, admixture mapping performs many fewer independent tests across the genome than current genome-wide association analysis. Therefore, admixture mapping can be more powerful because of the smaller penalty due to multiple tests. In this chapter, I introduce the theory behind admixture mapping and how we conduct the analysis in practice. PMID- 22307715 TI - Identifying gene interaction networks. AB - In this chapter, we introduce interaction networks by describing how they are generated, where they are stored, and how they are shared. We focus on publicly available interaction networks and describe a simple way of utilizing these resources. As a case study, we used Cytoscape, an open source and easy-to-use network visualization and analysis tool to first gather and visualize a small network. We have analyzed this network's topological features and have looked at functional enrichment of the network nodes by integrating the gene ontology database. The methods described are applicable to larger networks that can be collected from various resources. PMID- 22307716 TI - Structural equation modeling. AB - Structural equation modeling (SEM) is a multivariate statistical framework that is used to model complex relationships between directly and indirectly observed (latent) variables. SEM is a general framework that involves simultaneously solving systems of linear equations and encompasses other techniques such as regression, factor analysis, path analysis, and latent growth curve modeling. Recently, SEM has gained popularity in the analysis of complex genetic traits because it can be used to better analyze the relationships between correlated variables (traits), to model genes as latent variables as a function of multiple observed genetic variants, and assess the association between multiple genetic variants and multiple correlated phenotypes of interest. Though the general SEM framework only allows for the analysis of independent observations, recent work has extended SEM for the analysis of general pedigrees. Here, we review the theory of SEM for both unrelated and family data, the available software for SEM, and provide an example of SEM analysis. PMID- 22307717 TI - Genotype calling for the Affymetrix platform. AB - The analysis of high-throughput genotyping data in genome-wide association (GWA) studies has become a standard approach in genetic epidemiology. Data of high quality are crucial for the success of these studies. The first step in the statistical analysis is the generation of genotypes from signal intensities, and several approaches have been proposed for obtaining as accurate genotypes as possible. For the Affymetrix Genome-Wide Human SNP Array 6.0, the genotype calling algorithms Birdseed and CRLMM are commonly used in applications. After a brief description of the statistical methods for both algorithms, their usage is described in detail. Links are provided to the software and to sample code for the installation and execution of the algorithms. Additionally, a suggestion for processing the result files is made. PMID- 22307718 TI - Genotype calling for the Illumina platform. AB - Genome-wide association studies have been made possible because of advancements in the design of genotyping technologies to assay a million or more single nucleotide polymorphisms (SNPs) simultaneously. This has resulted in the introduction of automated and unsupervised statistical approaches for translating the probe hybridization intensities into the actual genotype calls. This chapter aims to provide an introduction to this process of genotype calling, highlighting in particular the design and approach used for the Illumina BeadArray platforms that are commonly used in large-scale genetic studies. The chapter also provides detailed instructions for preparing the input files required as well as the actual Linux commands and options to execute the ILLUMINUS software. Finally, it concludes with a brief exposition on the different outcomes from genotype calling and the use of perturbation analysis for identifying SNPs with erroneous genotype calls. PMID- 22307719 TI - Comparison of requirements and capabilities of major multipurpose software packages. AB - The aim of this chapter is to introduce the reader to commonly used software packages and illustrate their input requirements, analysis options, strengths, and limitations. We focus on packages that perform more than one function and include a program for quality control, linkage, and association analyses. Additional inclusion criteria were (1) programs that are free to academic users and (2) currently supported, maintained, and developed. Using those criteria, we chose to review three programs: Statistical Analysis for Genetic Epidemiology (S.A.G.E.), PLINK, and Merlin. We will describe the required input format and analysis options. We will not go into detail about every possible program in the packages, but we will give an overview of the packages requirements and capabilities. PMID- 22307720 TI - Bottom, crowned with an ass's head: does an inversion in thinking portend the end of Enlightenment science? PMID- 22307721 TI - European Miocene hominids and the origin of the African ape and human clade. AB - In 1871, Darwin famously opined, "In each great region of the world the living mammals are closely related to the extinct species of the same region. It is therefore probable that Africa was formerly inhabited by extinct apes closely allied to the gorilla and chimpanzee; and as these two species are now man's nearest allies, it is somewhat more probable that our early progenitors lived on the African continent than elsewhere." Although this quote is frequently recalled today, Darwin's next line is rarely acknowledged: "But it is useless to speculate on this subject, for an ape nearly as large as a man, namely the Dryopithecus of Lartet, which was closely allied to the anthropomorphous Hylobates, existed in Europe during the Upper Miocene period; and since so remote a period the earth has certainly undergone many great revolutions, and there has been ample time for migration on the largest scale." PMID- 22307722 TI - European neolithization and ancient DNA: an assessment. AB - Neolithic processes underlying the distribution of genetic diversity among European populations have been the subject of intense debate since the first genetic data became available. However, patterns observed in the current European gene pool are the outcome of Paleolithic and Neolithic processes, overlaid with four millennia of further developments. This observation encouraged paleogeneticists to contribute to the debate by directly comparing genetic variation from the ancient inhabitants of Europe to their contemporary counterparts. Pre-Neolithic and Neolithic paleogenetic data are becoming increasingly available for north and northwest European populations. Despite the numerous problems inherent in the paleogenetic approach, the accumulation of ancient DNA datasets offers new perspectives from which to interpret the interactions between hunter-gatherer and farming communities. In light of information emerging from diverse disciplines, including recent paleogenetic studies, the most plausible model explaining the movement of Neolithic pioneer groups in central Europe is that of leapfrog migration. PMID- 22307724 TI - An efficient computational model to predict the synthetic utility of heterocyclic arynes. AB - Think before you act: a computational approach is reported for evaluating the synthetic potential of heterocyclic arynes. Routine and rapid calculations of arene dehydrogenation energies and aryne angle distortion predict the likelihood that a given hetaryne can be generated, as well as the degree of regioselectivity expected in a reaction between a given hetaryne and a nucleophilic trapping agent. PMID- 22307725 TI - Clinical and molecular delineation of 16p13.3 duplication in a patient with congenital heart defect and multiple congenital anomalies. PMID- 22307726 TI - Efficient synthesis of C2v-symmetrical pentakisadducts of C60 as versatile building blocks for fullerene architectures that involve a mixed octahedral addition pattern. AB - We report here on the selective synthesis of fullerene pentakisadducts 3 with an incomplete octahedral addition pattern by means of mixed [5:1]hexakisadducts 1 that involve an isoxazoline moiety as a protection group. The isoxazoline addend can be cleanly cleaved by irradiation with light. By using this protection deprotection strategy, a variety of fullerene pentakisadducts 3 were synthesized in 29-44% overall yield without the need of HPLC purification. This novel photolytic deprotection of 1 can be explained by an initial electron transfer that leads to a biradical, which can easily eliminate the isoxazoline added. The very efficient and straightforward syntheses of the bisfullerene 4 and the globular hexakisadduct 7, each of which involves mixed octahedral addition patterns, clearly demonstrate the advantage of fullerene pentakisadducts 3 as suitable precursors for the construction of highly functional and complex [5:1]hexakisadduct architectures. Complete structural characterization of all new compounds was carried out by MALDI mass spectrometry, UV/Vis, FTIR, (1)H NMR and (13)C NMR spectroscopy, as well as X-ray diffraction. PMID- 22307727 TI - Comparison of two measures of gestational age among low income births. The potential impact on health studies, New York, 2005. AB - Recently, the National Association for Public Health Statistics and Information Systems considered changing the definition of gestational age from the current definition based on mother's last normal menstrual period (LMP) to the clinical/obstetric estimate determined by the physician (CE).They determined additional information was needed. This study provides additional insight into the comparability of the LMP and CE measures currently used on vital records among births at risk for poor outcomes. The data consisted of all New York State (NYS) (excluding New York City) singleton births in 2005 among mothers enrolled in the NYS Women Infants and Children (WIC) program during pregnancy. Prenatal WIC records were matched to NYS' Statewide Perinatal Data System. The analysis investigates differences between LMP and CE recorded gestations. Relative risks between risk factors and preterm birth were compared for LMP and CE. Exact agreement between gestation measures exists in 49.6% of births. Overall, 6.4% of records indicate discordance in full term/preterm classifications; CE is full term and LMP preterm in 4.9%, with the converse true for 1.5%. Associations between risk factor and preterm birth differed in magnitude based on gestational age measurement. Infants born to mothers with high risk indicators were more likely to have a CE of preterm and LMP full term. Changing the measure of gestational age to CE universally likely would result in overestimation of the importance of some risk factors for preterm birth. Potential overestimation of clinical outcomes associated with preterm birth may occur and should be studied. PMID- 22307728 TI - Older not wiser: risk of prenatal alcohol use by maternal age. AB - High levels of alcohol use among pregnant women have been associated with a spectrum of birth defects. Greater maternal age has been related to an increased risk of drinking during pregnancy. Although the context, process, and outcomes of pregnancy and alcohol use vary by maternal age, no studies have examined predictors of prenatal drinking by age. This study addresses this gap by examining potential risk factors associated with prenatal alcohol use (any versus none) by maternal age (<20, 20-25, 26-34, and 35 years or older). Descriptive and logistic regression analyses were completed on survey data from 9,004 pregnant women from the north central U.S. Descriptive statistics revealed teens in general had a higher level or greater occurrence of risk factors previously identified with prenatal drinking compared to older women, yet women of advanced maternal age (35 years or older) were most likely to drink alcohol during pregnancy. Based on the regression by age, 20-25 year old women had the greatest number of significant risk factors associated with prenatal drinking including being employed, white, unmarried, first birth, smoking prenatally, greater levels of depressed mood, and more experiences related to alcohol abuse. The number and patterns of significant predictors of drinking alcohol while pregnant by age encourage greater investigation of other social, contextual factors that might contribute to the risk of prenatal drinking. This is especially salient for women of advanced maternal age, for whom very few significant predictors emerged. PMID- 22307729 TI - Gadd45a and Gadd45b modulate innate immune functions of granulocytes and macrophages by differential regulation of p38 and JNK signaling. AB - Gadd45 proteins function as stress sensors in response to various physiological and environmental stressors, interacting with other cellular proteins implicated in cellular stress responses, including p38 and JNK. This study shows that mice lacking either Gadd45a or Gadd45b are defective in the recruitment of granulocytes and macrophages to the intra-peritoneal cavity following intra peritoneal administration of the bacterial cell wall pathogen-associated molecular pattern lipopolysaccharide (LPS). Bone marrow derived granulocytes and macrophages lacking either Gadd45a or Gadd45b are shown to be impaired in their chemotactic response to LPS, as well as other inflammatory stimuli such as N formyl-methionine-leucine-phenylalanine and IL-8. Evidence was obtained also implicating Gadd45a and Gadd45b in other myeloid innate immune functions, including reactive oxygen species production, phagocytosis, and adhesion. Gadd45a and Gadd45b activation of p38 kinase was implicated in the response of granulocytes to LPS mediated chemotaxis, whereas Gadd45a and Gadd45b curtailment of JNK activation was linked to chemotaxis of macrophages in response to LPS. Collectively, these data highlight a novel role for both Gadd45a and Gadd45b in myeloid innate immune functions by differential modulation of p38 and JNK signaling in granulocytes compared to macrophages. PMID- 22307730 TI - A highly diastereoselective three-component tandem 1,4-conjugated addition cyclization reaction to multisubstituted pyrrolidines. AB - A highly diastereoselective three-component tandem 1,4-conjugate addition cyclization reaction of diazoacetophenones with anilines and unsaturated ketoesters was developed. The reaction provides general, easy, and highly efficient access to multisubstituted pyrrolidines in good yield with high diastereoselectivity. PMID- 22307731 TI - Electrophilic and nucleophilic enzymatic cascade reactions in biosynthesis. AB - The biosynthesis of cyclic terpenoids and polyethers involves enzyme-initiated cascade reactions for ring formation. While the former are obtained by electrophilic cascades through carbenium ions as intermediates, cyclic polyethers are formed by nucleophilic cascade reactions of (poly)epoxide precursors. These mechanistically complementary pathways follow common principles via (i) triggering of the cascade by forming a reactive intermediate ('initiation'), (ii) sequential 'proliferation' of the cyclization and finally (iii) 'termination' of the cascade. As analyzed in this concept paper, the multiplicity of precursors, combined with various initiation and termination routes and kinetically favored or disfavored cyclization modes accounts for the enormous diversity in cyclic terpenoid and polyether scaffolds. Although the essential role of enzymes in the triggering of these cascades is reasonably well understood, remarkably little is known about their influence in proliferation reactions, especially those implying kinetically disfavored (anti-Markovnikov and anti-Baldwin) routes. Mechanistic analysis of enzymatic cascade reactions provides biomimetic strategies for natural product synthesis. PMID- 22307732 TI - Particle size distribution of ambient aerosols in an industrial area. AB - Aerosol samples of PM(10) and PM(2.5) were collected from 38 sampling locations in and around the industrial area. The 24 h average mass concentration of PM(10) and PM(2.5) was 137.5 and 61.5 MUg/m(3) respectively during summer, 122 and 97.5 MUg/m(3) respectively in winter and 70 and 54 MUg/m(3) respectively during post monsoon season. The relative contribution of coarse, fine and ultrafine particle to ambient air was analyzed for its temporal and seasonal variability in an industrialized area. This paper aims to establish baseline between PM(10) and PM(2.5) mass concentration levels. PMID- 22307733 TI - Decontamination of chlorantraniliprole residues on cabbage and cauliflower through household processing methods. AB - A supervised field trial was conducted to study the residues of chlorantraniliprole on cabbage and cauliflower. Three applications of chlorantraniliprole at 10 days interval were made @ 9.25 and 18.50 g a.i. ha(-1). The samples of marketable size heads and curds of cabbage and cauliflower were collected at 0 and 1 day after the last application. QuEChERS sample preparation was used for the determination of chlorantraniliprole residues on cabbage heads and cauliflower curds. The residues of chlorantraniliprole were quantified by high performance liquid chromatography (HPLC) with photo diode array (PDA) detector and confirmed by high performance thin layer chromatography (HPTLC). Washing of cabbage and cauliflower with tap water removed about 17%-40% of chlorantraniliprole residues. However, boiling removed 100% of chlorantraniliprole residues on cabbage and cauliflower in both the cases. PMID- 22307734 TI - Pregnancy outcome in women exposed to leflunomide before or during pregnancy. AB - OBJECTIVE: Findings from animal studies have suggested that leflunomide may be a human teratogen. In the only human cohort study published to date, an increase in adverse outcomes in pregnancies after exposure to leflunomide was not detected. The aim of the present analysis was to expand on the previously published data with a description of birth outcomes among women who did not meet the previous cohort study criteria but who were exposed to leflunomide either during pregnancy or prior to conception. METHODS: Data on pregnancy exposures and outcomes were collected from 45 pregnant women who had contacted counseling services of the Organization of Teratology Information Specialists in the US or Canada between 1999 and 2009. Sixteen women were exposed to leflunomide during the first trimester of pregnancy and 29 women were exposed preconception. RESULTS: All 16 of the pregnancies with leflunomide exposure during pregnancy and 27 (93%) of the pregnancies with exposure prior to conception resulted in liveborn infants. There were 2 infants with major malformations from mothers who were exposed during pregnancy, and no malformations reported in the preconception group. There was a potential known alternative etiology for at least some of the defects observed. CONCLUSION: These data provide additional reassurance to women who inadvertently become pregnant while taking leflunomide and who undergo the washout procedure, as well as women who discontinue the medication prior to conception but have no prepregnancy documentation of drug clearance. However, until more conclusive data become available, women receiving leflunomide should be advised to use contraceptive methods and avoid pregnancy. PMID- 22307735 TI - Antitumor effect of vandetanib through EGFR inhibition in head and neck squamous cell carcinoma. AB - BACKGROUND: The epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) have been implicated as therapeutic targets for head and neck squamous cell carcinoma (HNSCC). Vandetanib is a small-molecule tyrosine kinase inhibitor (TKI) with dual specificity for EGFR and VEGFR. Here we characterize the phenotypic and biochemical effects of vandetanib on various HNSCC cell lines. METHODS: In vitro models were used for studying tumor cell viability, invasion, and signaling as well as in vivo xenograft models. RESULTS: Treatment with vandetanib reduced viability, invasion, and tumor growth of HNSCC cell lines. Phosphorylation levels of mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) were reduced in vandetanib-treated HNSCC cells. Additionally, vandetanib abrogates EGF-induced STAT3 activity and STAT3 target gene expression. CONCLUSIONS: We demonstrated that vandetanib inhibits the growth of head and neck cancer cell lines. The antitumor effects of vandetanib appear to be exerted via the EGFR inhibitory effect of the compound. PMID- 22307736 TI - Clinical course of rhinitis and changes in vivo and in vitro of allergic parameters in elderly patients: a long-term follow-up study. AB - Changes in rhinitis symptom severity tend to decrease with aging, but whether the decrease is associated with allergic skin test reactivity, serum total and specific IgE, and nasal eosinophils or determined only by aging is poorly understood. The aim of the study was to analyze sensitivity in vivo and in vitro some 15 years after primary testing, skin prick test (SPT), serum total and specific IgE, ratio sIgE/tIgE, and nasal eosinophils in order to evaluate changes due to age and changes due to the severity of rhinitis symptoms. One hundred and eight rhinitis patients who had been investigated in 1995 were re-interviewed and their current allergy re-assessed after a follow-up of 15 years. All patients were SPT with eight common allergens in the area of Palermo (Italy). Rhinitis symptoms tended, on average, to have become milder at the follow-up. All parameters examined showed a decreasing trend in older age groups over the period between the two investigations. Rhinitis symptoms tend to become milder and the allergic parameters both in vivo and in vitro usually decrease in the long run; however, the changes in rhinitis symptoms appear to be related to changes in the nasal eosinophils, independently of SPT and serum-specific IgE. PMID- 22307737 TI - Chemical-assisted thermal disproportionation of porous silicon monoxide into silicon-based multicomponent systems. AB - Under the surface: Ag nanoparticles are deposited onto the surface of commercially available SiO particles, and subsequent chemical etching results in the formation of nanoporous SiO without changing the chemical and physical properties of the original SiO. Moreover, chemical-assisted thermal annealing produces a shape-preserving Si-based multicomponent system, which exhibits high performance electrochemical properties. PMID- 22307738 TI - Behavioral genetics of affective and anxiety disorders. AB - As shown by clinical genetic studies, affective and anxiety disorders are complex genetic disorders with genetic and environmental factors interactively determining their respective pathomechanism. Advances in molecular genetic techniques including linkage studies, association studies, and genome-wide association studies allow for the detailed dissection of the genetic influence on the development of these disorders. Besides the molecular genetic investigation of categorical entities according to standardized diagnostic criteria, intermediate phenotypes comprising neurobiological or neuropsychological traits (e.g., neuronal correlates of emotional processing) that are linked to the disease of interest and that are heritable, have been proposed to be closer to the underlying genotype than the overall disease phenotype. These intermediate phenotypes are dimensional and more precisely defined than the categorical disease phenotype, and therefore have attracted much interest in the genetic investigation of affective and anxiety disorders. Given the complex genetic nature of affective and anxiety disorders with an interaction of multiple risk genes and environmental influences, the interplay of genetic factors with environmental factors is investigated by means of gene-environment interaction (GxE) studies. Pharmacogenetic studies aid in the dissection of the genetically influenced heterogeneity of psychotropic drug response and may contribute to the development of a more individualized treatment of affective and anxiety disorders. Finally, there is some evidence for genetic factors potentially shared between affective and anxiety disorders pointing to a possible overlapping phenotype between anxiety disorders and depression. PMID- 22307739 TI - Reaction kinetics of dye decomposition processes monitored inside a photocatalytic microreactor. AB - The photocatalytic decomposition processes of several kinds of dyes were monitored in real-time, in a TiO(2)-immobilized microcapillary. Their fluorescence spectra were measured directly from the UV-irradiated area. The photocatalytic reactions proceeded two orders of magnitude faster in the microcapillary than in a bulk reaction, and intermediate species were easily observed, due to their high concentrations compared with those of the reactants. Even for molecules that were not originally fluorescent, fluorescence was detected for the reactants or intermediate species of all the molecules studied. Photocatalytic reactions are typically analyzed in terms of pseudo-first-order or Langmuir-Hinshelwood reaction mechanisms, but it was ascertained that all of the dyes investigated in this study decomposed via a multi-step reaction such as a simple multi-step reaction, a self-catalytic reaction, and further, a more complicated reaction, depending on the molecular structure. These reactions were simulated using models based on the reaction kinetics, and reaction mechanisms were assigned to each type of dye. The fact that intermediate species (which are difficult to observe using conventional analytical methods) were successfully detected meant that mechanisms for different dyes could be further clarified. PMID- 22307740 TI - Sudden cardiac death caused by coronary vasculitis. AB - Coronary vasculitis is a rare and diagnostically challenging cause of sudden cardiac death (SCD). There are currently no large-scale series on this rare entity. A retrospective non-case-control observational study of SCD with coronary vasculitis referred to a tertiary cardiac pathology referral centre at the National Heart and Lung Institute at the Royal Brompton Hospital between 1996 and 2010 was completed. Ten cases of SCD with coronary artery vasculitis were retrieved from a database of 1,980 SCD cases (0.5%) with a 1:1 male/female ratio; median age was 39 years and range 15-71 years. Six deaths occurred in hospital following symptoms or cardiac arrest in the community; the remaining died at rest at home (n = 4). Appearances ranged from aneurysms of the coronary artery to occlusive lesions mimicking atheroma or masses imitating tumour. Types of vasculitis detected were: eosinophilic (n = 5), two associated with Churg-Strauss syndrome; lymphoplasmacytic vasculitis (n = 4); and idiopathic giant cell arteritis (n = 1). This study shows coronary vasculitis as a rare cause of SCD with a variable macroscopic and microscopic presentation that pathologists need to be aware of. PMID- 22307741 TI - Nine years interval between first and second bone marrow transplantations and subsequent long-term survival--a case of acute myeloid leukemia with MLL-AF6 fusion gene. PMID- 22307742 TI - Adams-Oliver syndrome and portal hypertension: fortuitous association or common mechanism? AB - Adams-Oliver syndrome (AOS) is a rare condition defined by combination of cutis aplasia and transverse limb abnormalities. Some authors have described a possible association between this syndrome and portal hypertension (PH) due to hepatoportal sclerosis (HPS). We present a boy with AOS who developed a progressive splenomegaly and hypersplenism at the age of 2 months, and was admitted for acute gastrointestinal bleeding (GI) at the age of 9 months. Subsequently, we documented an extrahepatic portal vein obstruction and esophageal varices. After several episodes of cataclysmic upper GI bleeding a mesentero-portal shunt (MPS) was performed at 10 months. The shunt thrombosed, and after three failed attempts of thrombectomy, it was removed. One month later a splenorenal shunt was performed, and this closed spontaneously by 3 years. The patient suffered from ischemic stroke after placing the first shunt, and has spastic diplegia, left frontal lobe epilepsy, hyperactivity and attention deficit disorder, and severe psychomotor delay. At 11 years and he presented with chronic liver failure and hyperammonemia and coagulopathy. We hypothesize that there may be an early embryonic vascular abnormality (vascular disruption) that may explain these vascular phenomena. PMID- 22307743 TI - Phenotypic characterization of transgenic mice harboring Nf1+/- or Nf1-/- osteoclasts in otherwise Nf1+/+ background. AB - Skeletal abnormalities in neurofibromatosis type 1 syndrome (NF1) are observed in ~50% of patients. Here, we describe the phenotype of Nf1(Ocl) mouse model with Nf1-deficient osteoclasts. Nf1Ocl mice with Nf1+/- or Nf1-/- osteoclasts in otherwise Nf1+/+ background were successfully generated by mating parental Nf1flox/flox and TRAP-Cre mice. Contrary to our original hypothesis, osteoporotic or fragile bone phenotype was not observed. The uCT analysis revealed that tibial bone marrow cavity, trabecular tissue volume, and the perimeter of cortical bone were smaller in Nf1 Ocl-/- mice compared to Nf1 Ocl+/+ control mice. Nf1 Ocl-/- mice also a displayed narrowed growth plate in the proximal tibia. In vitro analysis showed increased bone resorption capacity and cytoskeletal changes including irregular cell shape and abnormal actin ring formation in Nf1-/- osteoclasts. Surprisingly, the size of spleen in Nf1 Ocl-/- mice was two times larger than in controls and histomorphometric analysis showed splenic megakaryocytosis. In summary, Nf1Ocl mouse model presented with a mild but specific bone phenotype. This study shows that NF1-deficiency in osteoclasts may have a role in the development of NF1-related skeletal abnormalities, but Nf1 deficiency in osteoclasts in Nf1+/+ background is not sufficient to induce skeletal abnormalities analogous to those observed in patients with NF1. PMID- 22307744 TI - Pathology of urethral fibromuscular system related to parturition-induced stress urinary incontinence and TGF-beta1/Smad pathway. AB - To study pathological changes of fibromuscular system and the role of TGF beta1/Smad pathway in the urethra of a parturition-induced stress urinary incontinence (SUI) rat model. Twenty-eight 8-week-old Sprague-Dawley female rats at gestational day 16 were used and randomized into two groups: sham group and SUI group. After delivery, rats in the SUI group underwent postpartum vaginal balloon dilation and bilateral ovariectomy. 1 month after ovariectomy, urodynamics was assessed. Histological examination (Masson's trichrome stain, picrosirius red stain, Hart's elastin stain, Gordon & Sweet's stain, and immunohistochemical stain) and Western blot were performed on urethral tissues. Both leak point pressure and maximal bladder capacity were significantly decreased in the balloon-injured ovariectomized rats, compared with the sham rats. Muscle was significantly decreased in the urethra of SUI rats compare with sham rats. Collagen I/III and reticular fibers from SUI group were also significantly lower than sham group. Meanwhile, elastic fibers and reticular fibers showed fragmentation and disorganization indicating impairment in the fibromuscular system in SUI rats. TGF-beta1, MMP-9, and phosphorylated Smad2 (p Smad2) were expressed significantly higher in SUI than in sham rats. Simulated birth trauma and menopause induced an upregulation of the TGF-beta1/Smad pathway and impairment of the fibromuscular system in the urethra. PMID- 22307746 TI - Macrophages actively accumulate malonyldialdehyde-modified but not enzymatically oxidized low density lipoprotein. AB - In this study, we show that low density lipoproteins (LDL) from human blood plasma which was oxidized by animal C-15 lipoxygenase is taken up by cultivated human macrophages with the same effectiveness as with non-oxidized (native) LDL. At the same time malonyldialdehyde-modified LDL is captured by cultivated macrophages very actively. Based on differences in catabolism of LDL with various levels of primary and secondary products of free-radical oxidation, it was offered to discriminate between the oxidized LDL itself (lipohydroperoxide-rich LDL) and the LDL that was chemically modified by free-radical oxidation secondary products of aldehyde nature. In this respect, aldehyde-modified but not oxidized (lipohydroperoxide-containing) LDL is atherogenic. PMID- 22307745 TI - UVA/B exposure promotes the biosynthesis of dehydroretinol in cultured human keratinocytes. AB - Retinol and its metabolites modulate epithelial differentiation and serve as cellular UV sensors through changes in retinoid status. Of note is the dehydroretinol family which may serve functions distinct from parental retinol. This study focuses on the metabolism of this family and its potential participation in the response of normal epidermal human keratinocytes to UV irradiation. There were three findings. First, keratinocytes contain two pools of dehydroretinyl esters, one of which is shielded from UVB-, but not from UVA induced decomposition. Second, using a novel in vitro assay we demonstrated that both UVA and UVB promote dehydroretinol biosynthesis in keratinocytes, but only UVB exposure promotes retinoid ester accretion by enhancing the activity of at least one acyl transferase. Finally, dehydroretinol sufficiency reduces UVA/B driven apoptosis more effectively than retinol sufficiency. This may in part be due to differences in the expression of Fas ligand, which we found to be upregulated by retinoic acid, but not dehydroretinoic acid. These observations implicate a role of dehydroretinol and its metabolites in UVA/B adaptation. Thus, the keratinocyte response to UV is jointly shaped by both the retinoids and dehydroretinoids. PMID- 22307747 TI - Love hurts (in more ways than one): specificity of psychological symptoms as predictors and consequences of romantic activity among early adolescent girls. AB - OBJECTIVE: Research has linked adolescent romantic and sexual activities to depressive symptoms. The current study examines whether such activities are uniquely linked to depressive symptoms versus symptoms of other disorders (including anxiety, externalizing, and eating disorders), and whether co occurring symptoms more precisely account for the association between depressive symptoms and romantic involvement. METHOD: Early adolescent girls (N = 83; mean age = 13.45) participated in baseline and 1-year follow up data collection. RESULTS: Romantic (i.e., dating and sexual) activities were longitudinally related to numerous types of symptoms. The association between depressive symptoms and romantic variables remained when considering co-occurring symptoms. Girls with more comorbid disorders reported more romantic activities. CONCLUSIONS: Results suggest that the maladaptive consequences and precipitants of adolescent romantic activities extend beyond depression, but also imply that this association is not secondary to comorbid symptoms. Future work should clarify causal pathways. PMID- 22307748 TI - Simultaneous squamous cell carcinoma with primary malignant fibrous histiocytoma of the larynx: a case report. AB - Simultaneous multiple malignancies of the larynx are rarely reported. In this study, we describe a case with simultaneous laryngeal, moderately differentiated squamous cell carcinoma (SCC) and primary malignant fibrous histiocytoma (MFH) in a patient presenting with progressive hoarseness and without cervical lymphadenopathy. The clinical presentation, intraoperative findings, radiographic images and pathology slides are presented. The diagnosis was confirmed using H&E staining and immunohistochemical testing. A partial laryngectomy with bilateral neck selective dissection was performed. The patient survived for more than 46 months following surgery without recurrence or metastasis. To our knowledge, this is the first report of a case with simultaneous laryngeal SCC and primary MFH in the English literature. The results indicate that the markers used to assess the prognosis of MFH may also be used to assess simultaneous laryngeal SCC and primary MFH, and that laryngectomy to preserve function may be performed in early stage patients. PMID- 22307749 TI - An alternative approach: a highly selective dual responding fluoride sensor having active methylene group as binding site. AB - A newly designed phosphonium derivative (L) having active methylene functionality, shows unusual preference towards F(-) over all other anions. The binding process through C-H...F(-) hydrogen bond formation was probed by monitoring the changes in either electronic or luminescence spectra. Changes in both cases are significant enough to allow visual detection. The loss of molecular flexibility of L on forming L.F(-) effectively interrupts the non radiative deactivation pathway and accounts for the observed switch on fluorescence response. The results of the time-resolved emission studies for L and L.F(-) using a time-correlated single photon counting technique further corroborate this presumption. The excellent preference of L towards F(-) is attributed to an efficient hydrogen bonding interaction between the strongly polarized methylene protons and F(-), which delineates the subtle difference in the affinity among other competing anionic analytes like CN(-), H(2)PO(4)(-), CH(3)CO(2)(-), etc. The relative affinities of various anions and the preferential binding of F(-) to reagent L are also rationalized using computational studies. PMID- 22307750 TI - Celebrating 25 years of biomedical chromatography. A report on the Royal Society of Chemistry, Separation Science Group Meeting, held at the Wellcome Centre, London, 25-26 November 2011. PMID- 22307751 TI - Postoperative functional rehabilitation after repair of quadriceps tendon ruptures: a comparison of two different protocols. AB - PURPOSE: Early functional rehabilitation after surgical tendon repair facilitates the healing process and leads to improved joint function. There is a paucity of studies commenting on rehabilitation after surgical repair of ruptured quadriceps tendons, and most surgeons prefer a prolonged period of immobilization and protected weight bearing. The purpose of the present study is to compare the clinical outcome after a more functional and after a rather restrictive postoperative rehabilitation protocol. METHODS: All consecutive patients were included who had a surgical repair of a primary unilateral quadriceps tendon rupture in one of the two participating hospitals and a minimum follow-up of 24 months. Patients of site A were only allowed limited flexion and weight bearing while patients from site B were allowed early functional rehabilitation with full weight bearing. Clinical outcome was measured with the subjective IKDC form. Fisher's exact test and Mann-Whitney U test were used for statistical analysis. RESULTS: Sixty-six patients were included in the study. Twenty-eight patients (Group A) were treated with restrictive and 38 patients (Group B) with early functional postoperative rehabilitation. The two groups did not differ in terms of demographic characteristics. Clinical follow-up was available for 95% of patients after an average of 4.5 years. No clinical difference was identified with the use of IKDC form. Patients of group A returned to work an average of 10 days later than patients from group B, but this difference was not significant. Two re-ruptures were observed in each group. There was no significant difference in terms of complication quality or quantity. CONCLUSION: Early functional postoperative mobilization with full weight bearing after primary repair of a quadriceps tendon rupture is safe and will not lead to inferior clinical outcome or an increased complication rate. LEVEL OF EVIDENCE: Therapeutic, III. PMID- 22307752 TI - Treatment of fixed knee flexion deformity by anterior distal femoral stapling. AB - PURPOSE: The treatment of fixed knee flexion deformity through anterior distal femoral stapling has been investigated in only two studies so far, with promising results. The aim of the present study was to determine whether this technique might improve fixed knee flexion deformity in a series of growing children and adolescents with different conditions. Follow-up examinations were continued after staple removal in terms of a possible impairment of this deformity. METHODS: We reviewed the medical records of all patients with fixed knee flexion deformity who had been treated by anterior distal femoral stapling at our institution. Twenty patients (37 knees) with a mean age of 12.7 years met the inclusion criteria (>12 months of follow-up; no additional procedures to correct fixed knee flexion deformity such as hamstring lengthening or posterior capsulotomy) and were evaluated in this study. RESULTS: The mean fixed knee flexion deformity significantly improved from 21.4 degrees (SD = 11.6) preoperatively to 7.0 degrees (SD = 9.8) after a mean follow-up of 35.3 months. Young patients (<12 years) revealed superior improvement of this deformity, and especially children with distinct fixed knee flexion deformity of 30 degrees or greater had benefit from early treatment. Impairment of flexion deformity was only seen in one patient (2 knees) after staple removal. CONCLUSIONS: Our results demonstrate that anterior distal femoral stapling is an effective method for the treatment of fixed knee flexion deformity in growing children and adolescents. Rare complications, immediate mobilization, and a low recurrence rate after staple removal provide obvious advantages of this minimally invasive procedure. LEVEL OF EVIDENCE: Retrospective therapeutic study, Level IV. PMID- 22307753 TI - Second, third, and fourth head and neck tumors. A progressive decrease in survival. AB - BACKGROUND: Patients with a first head and neck carcinoma have a high risk of successive neoplasms, many of which appear again in the head and neck. Second head and neck tumors have a poorer prognosis than first tumors, but data about the prognosis of third and fourth tumors in the head and neck are lacking. METHODS: We carried out a retrospective study of 4298 patients with a primary head and neck carcinoma. Survival and the characteristics of the first tumor, second tumor, and any successive tumors in the head and neck were analyzed. RESULTS: Second and successive tumors showed a tendency to appear more frequently in the oral cavity and oropharynx and had a lower stage than that of index tumors. Five-year survival rates after a first, second, third, and fourth tumors in the head and neck were 67.6%, 56.1%, 45.0%, and 32.1%, respectively. CONCLUSION: Survival decreased progressively with every new head and neck tumor. PMID- 22307754 TI - Chemical synthesis of an erythropoietin glycoform containing a complex-type disialyloligosaccharide. PMID- 22307755 TI - Evidence that a single monomer of Spx can productively interact with RNA polymerase in Bacillus subtilis. AB - Spx activates transcription initiation in Bacillus subtilis by directly interacting with the C-terminal domain of the RNA polymerase (RNAP) holoenzyme alpha subunit, which generates a complex that recognizes the promoter regions of genes within the Spx regulon. Many Gram-positive species possess multiple paralogs of Spx, suggesting that two paralogous forms of Spx could simultaneously contact RNAP. The composition of Spx/RNAP was examined in vitro using an Spx variant (SpxDeltaCHA) bearing a 12-amino-acid deletion of the C terminus (SpxDeltaC) and a hemagglutinin (HA) epitope tag and Spxc-Myc, a full-length Spx with a C-terminal myelocytomatosis oncoprotein (c-Myc) epitope tag. All Spx/RNAP complexes bearing deletion or C-terminal-tagged variants were transcriptionally active in vivo and in vitro. Reaction mixtures containing SpxDeltaCHA and Spxc Myc combined with RNAP were applied to either anti-HA or anti-c-Myc affinity columns. Eluted fractions contained RNAP with only one of the epitope-tagged Spx derivatives. The resin-bound RNAP complex bearing a single epitope-tagged Spx derivative was transcriptionally active. In vivo production of SpxDeltaC and SpxDeltaCHA followed by anti-HA affinity column chromatography of a cleared lysate resulted in retrieval of Spx/RNAP with only the SpxDeltaCHA derivative. Binding reactions that combined active Spxc-Myc, inactive Spx(R60E)DeltaCHA, and RNAP, when applied to the anti-HA affinity column, yielded only inactive Spx(R60E)DeltaCHA/RNAP complexes. The results strongly argue for a model in which a single Spx monomer engages RNAP to generate an active transcriptional complex. PMID- 22307756 TI - Genome-wide definition of the SigF regulon in Mycobacterium tuberculosis. AB - In Mycobacterium tuberculosis the alternative sigma factor SigF controls the expression of a particular subset of genes by altering RNA polymerase specificity. Here, we utilize two genome-wide approaches to identify SigF-binding sites: chromatin immunoprecipitation (ChIP-on-chip) and microarray analysis of SigF-mediated transcripts. Since SigF is not an abundant protein in the logarithmic phase of growth, a pristinamyin IA-inducible system was used to control its expression. We identified 67 high-affinity SigF-binding sites and 16 loci where a SigF promoter directs the expression of a transcript. These loci include sigF itself, genes involved in lipid and intermediary metabolism and virulence, and at least one transcriptional regulator (Rv2884), possibly acting downstream of SigF. In addition, SigF was also found to direct the transcription of the gene for small RNA F6. Many loci were also found where SigF may be involved in antisense transcription, and in two cases (Rv1358 and Rv1870c) the SigF-dependent promoter was located within the predicted coding sequence. Quantitative PCR confirmed the microarray findings and 5'-rapid amplification of cDNA ends was used to map the SigF-specific transcriptional start points. A canonical SigF consensus promoter sequence GGTTT-N((15-17))-GGGTA was found prior to 11 genes. Together, these data help to define the SigF regulon and show that SigF not only governs expression of proteins such as the virulence factor, HbhA, but also impacts novel functions, such as noncoding RNAs and antisense transcripts. PMID- 22307757 TI - The TonB3 system in the human pathogen Vibrio vulnificus is under the control of the global regulators Lrp and cyclic AMP receptor protein. AB - TonB systems transduce the proton motive force of the cytoplasmic membrane to energize substrate transport through a specific TonB-dependent transporter across the outer membrane. Vibrio vulnificus, an opportunistic marine pathogen that can cause a fatal septicemic disease in humans and eels, possesses three TonB systems. While the TonB1 and TonB2 systems are iron regulated, the TonB3 system is induced when the bacterium grows in human serum. In this work we have determined the essential roles of the leucine-responsive protein (Lrp) and cyclic AMP (cAMP) receptor protein (CRP) in the transcriptional activation of this system. Whereas Lrp shows at least four very distinctive DNA binding regions spread out from position -59 to -509, cAMP-CRP binds exclusively in a region centered at position -122.5 from the start point of the transcription. Our results suggest that both proteins bind simultaneously to the region closer to the RNA polymerase binding site. Importantly, we report that the TonB3 system is induced not only by serum but also during growth in minimal medium with glycerol as the sole carbon source and low concentrations of Casamino Acids. In addition to catabolite repression by glucose, l-leucine acts by inhibiting the binding of Lrp to the promoter region, hence preventing transcription of the TonB3 operon. Thus, this TonB system is under the direct control of two global regulators that can integrate different environmental signals (i.e., glucose starvation and the transition between "feast" and "famine"). These results shed light on new mechanisms of regulation for a TonB system that could be widespread in other organisms. PMID- 22307758 TI - Signal perception by the secretion stress-responsive CssRS two-component system in Bacillus subtilis. AB - The CssRS two-component system responds to heat and secretion stresses in Bacillus subtilis by controlling expression of HtrA and HtrB chaperone-type proteases and positively autoregulating its own expression. Here we report on the features of the CssS extracellular loop domain that are involved in signal perception and on CssS subcellular localization. Individual regions of the CssS extracellular loop domain contribute differently to signal perception and activation. The conserved hydrophilic 26-amino-acid segment juxtaposed to transmembrane helix 1 is involved in the switch between the deactivated and activated states, while the conserved 19-amino-acid hydrophobic segment juxtaposed to transmembrane 2 is required for signal perception and/or transduction. Perturbing the size of the extracellular loop domain increases CssS kinase activity and makes it unresponsive to secretion stress. CssS is localized primarily at the septum but is also found in a punctate pattern with lower intensity throughout the cell cylinder. Moreover, the CssRS-controlled HtrA and HtrB proteases are randomly distributed in foci throughout the cell surface, with more HtrB than HtrA foci in unstressed cells. PMID- 22307759 TI - Joint immobilization prevents murine osteoarthritis and reveals the highly mechanosensitive nature of protease expression in vivo. AB - OBJECTIVE: Mechanical joint loading is critical for the development of osteoarthritis (OA). Although once regarded as a disease of cartilage attrition, OA is now known to be controlled by the expression and activity of key proteases, such as ADAMTS-5, that drive matrix degradation. This study was undertaken to investigate the link between protease expression and mechanical joint loading in vivo. METHODS: We performed a microarray analysis of genes expressed in the whole joint following surgical induction of murine OA (by cutting the medial meniscotibial ligament). Gene expression changes were validated by reverse transcriptase-polymerase chain reaction in whole joints and microdissected tissues of the joint, including the articular cartilage, meniscus, and epiphysis. Following surgery, mouse joints were immobilized, either by prolonged anesthesia or by sciatic neurectomy. RESULTS: Many genes were regulated in the whole joint within 6 hours of surgical induction of OA in the mouse. These included Arg1, Ccl2, Il6, Tsg6, Mmp3, Il1b, Adamts5, Adamts4, and Adamts1. All of these were significantly regulated in the articular cartilage. When joints were immobilized by prolonged anesthesia, regulation of the vast majority of genes was abrogated. When joints were immobilized by sciatic neurectomy, regulation of selected genes was abrogated, and OA was prevented up to 12 weeks postsurgery. CONCLUSION: These findings indicate that gene expression in the mouse joint following the induction of OA is rapid and highly mechanosensitive. Regulated genes include the known pathogenic protease ADAMTS-5. Targeting the mechanosensing mechanisms of joint tissue may offer new strategies for disease modification. PMID- 22307760 TI - Health economic modelling of the cost-effectiveness of microalbuminuria screening in Switzerland. AB - PRINCIPLES: Current evidence indicates that chronic kidney disease (CKD) can be detected by simple laboratory tests. This study aimed to evaluate the cost effectiveness of microalbuminuria screening and subsequent treatment in different populations. METHODS: Cost-effectiveness of microalbuminuria screening in a cohort of simulated subjects aged >=50 years was assessed using a validated microsimulation model. Microalbuminuria screening was simulated for 1-, 2-, 5- or 10-year intervals and for 3 groups: diabetes (DM), hypertension but no diabetes (HTN), and no diabetes or hypertension. Positive microalbuminuria screening was followed by treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). The model outcomes evaluate costs from a health care system perspective. RESULTS: Screening of risk groups is cost effective at a 2-year interval for the DM group with an incremental cost effectiveness ratio (ICER) of 54,000 CHF/ Quality-Adjusted-Life-Years (QALY) and at a 5-year interval for the HTN group with an ICER of 33,000 CHF/QALY. Screening of the remaining population is cost-effective at a 10-year interval with an ICER of 34,000 CHF/QALY. The ICER improves with longer screening intervals for all groups. A probabilistic sensitivity analysis (PSA) confirmed 2-year, 5-year and 10-year intervals as the most cost-effective for the DM group, the HTN group and the remaining population respectively. CONCLUSIONS: Microalbuminuria screening can be considered cost-effective starting at the age of 50 years at bi-annual intervals for subjects with diabetes, at 5-year intervals for subjects with hypertension and at 10-year intervals for the remaining population. Our results indicate that early detection and treatment of CKD might lead to optimised patient care, and offer guidance for future implementation of CKD screening programmes. PMID- 22307761 TI - Malt-induced premature yeast flocculation: current perspectives. AB - Premature yeast flocculation (PYF) is a sporadic problem for the malting and brewing industries which can have significant financial and logistical implications. The condition is characterised by abnormally heavy (and sometimes early) flocculation of yeast during brewery fermentations. The resulting low suspended yeast cell counts towards the end of the fermentation can result in flavour defects and incomplete attenuation (fermentation of sugars to alcohol). Despite several decades of research into the phenomenon, its precise nature and mechanisms have not been fully elucidated. In part this is because the term PYF has become a 'catch-all' syndrome which can have multiple origins. Furthermore, there are complex interactions in the malting and brewing processes which together mean that the PYF status of a malt sample is hard to predict at a generic level. Whether or not PYF is observed depends not only on barley quality, but on process factors in the maltings and to a substantial extent on the brewing yeast strain concerned. This article highlights the significance of PYF, and reviews current knowledge relating to the origins of this complex phenomenon. PMID- 22307762 TI - Laser pulse trains for controlling excited state dynamics of adenine in water. AB - We investigate theoretically the control of the ultrafast excited state dynamics of adenine in water by laser pulse trains, with the aim to extend the excited state lifetime and to suppress nonradiative relaxation processes. For this purpose, we introduce the combination of our field-induced surface hopping method (FISH) with the quantum mechanical-molecular mechanical (QM/MM) technique for simulating the laser-driven dynamics in the condensed phase under explicit inclusion of the solvent environment. Moreover, we employ parametric pulse shaping in the frequency domain in order to design simplified laser pulse trains allowing to establish a direct link between the pulse parameters and the controlled dynamics. We construct pulse trains which achieve a high excitation efficiency and at the same time keep a high excited state population for a significantly extended time period compared to the uncontrolled dynamics. The control mechanism involves a sequential cycling of the population between the lowest and higher excited states, thereby utilizing the properties of the corresponding potential energy surfaces to avoid conical intersections and thus to suppress the nonradiative decay to the ground state. Our findings provide a means to increase the fluorescence yield of molecules with an intrinsically very short excited state lifetime, which can lead to novel applications of shaped laser fields in the context of biosensing. PMID- 22307763 TI - Gemcitabine in combination with vinorelbine in elderly patients with anthracycline- and taxane-pretreated metastatic breast cancer. AB - PURPOSE: To evaluate the efficacy and safety of gemcitabine in combination with vinorelbine in elderly patients with anthracycline- and taxane-pretreated metastatic breast cancer (MBC). PATIENTS AND METHODS: Elderly patients with MBC received gemcitabine 1,000 mg m(-2) and vinorelbine 25 mg m(-2) on days 1 and 8 every 3 weeks for a maximum of 6 cycles. The primary end points were objective response and toxicity. The secondary end points included progression-free survival (PFS), overall survival (OS), and prognostic factors associated with disease control, PFS, and OS. RESULTS: Fifty-one patients with a median age of 73 years (range, 65-84 years) were included. The response rate according to Response Evaluation Criteria in Solid Tumors was 33.3% (95% confidence interval [CI], 20.4 to 46.2%). At a median follow-up of 16.2 months, median PFS and OS were 6.2 (95% CI, 4.6 to 7.8) and 17.0 months (95% CI, 14.5 to 19.5), respectively. Grade 3 to 4 adverse events included neutropenia (25.5%), anemia (13.7%), thrombocytopenia (9.8%), fatigue (5.9%), constipation (3.9%), neuropathy (3.9%), and hepatotoxicity (3.9%). Neutropenic fever occurred in 2 patients. There was one toxic death due to massive gastrointestinal hemorrhage. The study of prognostic factors did not reveal any predictive factor of disease control, while response to treatment and Eastern Cooperative Oncology Group performance status was the main factor conditioning PFS and OS, respectively. CONCLUSION: Gemcitabine in combination with vinorelbine is active and safe in elderly patients with anthracycline- and taxane-pretreated metastatic breast cancer. PMID- 22307764 TI - Ultrastructural study of spermiogenesis and the spermatozoon of Acanthocephaloides incrassatus (Molin, 1858) (Acanthocephala, Paleacanthocephala, Arhythmacanthidae) from Anguilla anguilla (Pisces, Teleostei) in Urbino ponds (Corsica Island). AB - This study deals with first ultrastructure features of Acanthocephaloides incrassatus (Paleacanthocephala, Arhythmacanthidae), a parasite of the fish Anguilla anguilla, reported for the first time in a Mediterranean pond. The spermiogenesis of A. incrassatus shows original specificities which have never been pointed out to this day in ultrastructural studies on spermiogenesis: the centriolar derivative is divided into two parts of different densities: an electron-dense, and the other, electron-lucent; a ring form has been observed on each side of the axoneme; a centriole with one central element. After the elaboration of a flagellum of 9+2 pattern, the centriole migrates in a nuclear groove. Rapidly, the centriole disappears. Then, the flagellum migration occurs by a series of processes and gives rise to a spermatozoon. The spermatozoon of A. incrassatus presents its own specificities: it exhibits an evolution of the centriolar derivative characterized by only nine peripheral elements deprived of a central element in the anterior part, then nine peripheral and one central element, and finally, nine peripheral elements with two central elements. An assumption is emitted on a probable correspondence of the evolution of the derivative centriolar during the spermiogenesis and the evolution that occurs in the spermatozoon. Protein granules also show different sizes and forms, full or emptied of their contents compared with data on other Acanthocephala. PMID- 22307765 TI - Prognostic significance of T cell subsets in peripheral blood of B cell non Hodgkin's lymphoma patients. AB - The role of tumor-infiltrating T cell subsets in the prognosis of non-Hodgkin's lymphoma (NHL) has previously been reported. In the present study, we investigated the prognostic significance of different T cell subsets in the peripheral blood of NHL patients. Immunophenotyping was performed on the peripheral blood samples of 45 patients with newly diagnosed B cell NHL using flow cytometry. The relationship between T cell subsets of CD4+, CD8+, CD3+CD25+, CD4+CD25+, CD4+CD25high [as T regulatory cells (T reg)], and the CD4/CD8 ratio with international prognostic index (IPI) and response to therapy was determined. The percentages of CD3+, CD4+, and CD8+ T cells in the peripheral blood of the patients were 49.1+/-20.3%, 23.6+/-11%, and 31.4+/-14.4%, respectively (CD4/CD8 ratio: 0.92+/-0.6). There were 4.2+/-3.2% T reg cells. A study of the percentage of T cells in relation to IPI score showed a higher proportion of CD3+CD25+, CD4+, and CD4+CD25+ cells in low-risk patients compared with intermediate/high risk groups (p<0.05). The above cells, as well as CD4+CD25high T reg cells, indicated a positive correlation with complete remission (CR) and survival. CD4 positivity correlated significantly with survival and CR durations, which were longer in patients with >=20% CD4+ cells than those with <20% CD4+ cells, thus indicating the prognostic value of CD4+ T cells in NHL patients. There was no significant data on CD8+ cells as well as the CD4/CD8 ratio between distinct IPI groups and response to therapy. These data indicated the importance of CD4+ cells and the activation status of T cells in immunity against lymphoma and the prognostic implication of enumeration of these cells in NHL patients. PMID- 22307766 TI - Familial 16q24.3 microdeletion involving ANKRD11 causes a KBG-like syndrome. AB - Haploinsufficiency of ANKRD11 encoding ankyrin repeat domain-containing protein 11 was recently reported as the cause of a syndrome due to microdeletion, characterized by intellectual disability with minor facial anomalies and short stature. Most recently, intragenic mutations of ANKRD11 were found in a cohort of patients with KBG syndrome. KBG is an autosomal dominant intellectual disability syndrome characterized by short stature, characteristic facial appearance, macrodontia, and skeletal anomalies. It remains unknown if deletion of the entire ANKRD11 causes KBG syndrome. We present a mother and child with a heterozygous 365 Kb deletion at 16q24.3 containing ANKRD11, ZNF778, and SPG7 genes. The child presented with developmental delay, facial anomalies, hand anomalies, and a congenital heart defect. The mother has short stature, facial anomalies, macrodontia, hand anomalies, and learning disability. Both individuals had many findings reported in KBG syndrome and the family met the suggested diagnostic criteria. However, typical macrodontia with fused incisors, costovertebral anomalies, and delayed bone age were not present. We conclude that microdeletions involving ANKRD11 result in a phenotype similar to that of KBG syndrome. (c) 2012 Wiley Periodicals, Inc. PMID- 22307767 TI - alpha-Azido ketones. Part 7: synthesis of 1,4-disubstituted triazoles by the "click" reaction of various terminal acetylenes with phenacyl azides or alpha azidobenzo(hetera)cyclanones. AB - Copper(I)-catalyzed alkyne-azide 1,3-cycloaddition reaction (CuAAC, Sharpless Meldal reaction) of various alpha-azido ketones such as substituted 2 azidoacetophenones, 2-azidobenzosuberone and 3-azido(thio)chromanones with terminal alkynes was studied. The reaction resulted in the formation of the expected 1,2,3-triazoles in moderate to good yields although the reactivity was somewhat lower than in the case of simple azides. Reaction of ethynylchromones as alkynes gave interesting dichromonoid systems bridged by a triazole unit. PMID- 22307768 TI - Highly Z-selective asymmetric conjugate addition of alkynones with pyrazol-5-ones promoted by N,N'-dioxide-metal complexes. AB - Highly selective: the title reaction is achieved with high enantiomeric and geometric control and thermodynamically unstable (Z)-enone derivatives are obtained as the major products. The procedure tolerates a wide range of substrates to generate optically active pyrazolones with vinyl-substituted quaternary stereocenters. PMID- 22307769 TI - microRNAs as tumor inhibitors, oncogenes, biomarkers for drug efficacy and outcome predictors in lung cancer (review). AB - Lung cancer remains the leading cause of cancer-related death worldwide for both men and women, and non-small cell lung cancer (NSCLC) accounts for approximately 80% of all cases. Despite improvements in early diagnosis and newly developed therapies, the 5-year survival rate for NSCLC patients remains low (15%). Therapy in NSCLC has reached a plateau. Understanding genomic medicine may provide insight into the oncogenesis of lung cancer and open the door to molecular diagnosis, new biomarkers and a more accurate prognosis of lung cancer. It is well known that almost half of the genes regulated by microRNAs (miRNAs) are located in cancer-associated genomic regions. In the present study, we discuss the potential of miRNAs to function as suppressors and biomarkers for chemoresistance and prognosis of lung cancer. PMID- 22307770 TI - Vaginal repair of supratrigonal vesicovaginal fistulae--a 10-year review. AB - INTRODUCTION AND HYPOTHESIS: A 10-year retrospective study was done to determine the outcome of vaginal repair for supratrigonal vesicovaginal fistulae (VVF). METHODS: One hundred thirty-two urinary fistulae were managed from 2001 to 2011 which include 34 ureterovaginal and 98 lower urinary tract fistulae. Fifty-three out of 98 were supratrigonal VVF, 49 were of benign etiology and 4 were malignancy induced. Further analysis of 49 supratrigonal VVF of benign etiology revealed that 38 (77.5%) were of gynecological origin and 11 (22.5%) obstetric. Forty-three were primary and six were recurrent VVF. Thirty (61.2%) supratrigonal VVF were repaired vaginally and 19 (38.8 %) abdominally. Mean follow-up period was 51.7 months. RESULTS: The successful outcome for vaginal and abdominal repair was 86.7% and 100%, respectively (p value = 0.26). Overall, 91.8% supratrigonal VVF were cured at our first attempt. CONCLUSIONS: Majority of supratrigonal VVF can be approached vaginally with success rate comparable to abdominal approach. PMID- 22307772 TI - Parapharyngeal space tumors: another consideration for otalgia and temporomandibular disorders. AB - BACKGROUND: Parapharyngeal space (PPS) tumors are rare, accounting for 0.5% of all head and neck neoplasms. PPS tumors are difficult to diagnose due to limited presenting signs and symptoms and because of their location deep within the neck. METHODS AND RESULTS: A 60-year-old woman presented with complaints of otalgia, which appeared to be consistent with a temporomandibular disorder (TMD). Due to disproportionate symptoms, an MRI of the temporomandibular joints was ordered. The MRI revealed a mass within the PPS, which was later diagnosed as a mucoepidermoid carcinoma. A literature search failed to reveal otalgia, and facial pain, thought to be related to a TMD, as the primary presenting symptoms of a PPS neoplasm. CONCLUSION: Patients presenting with disproportionate signs and symptoms of a TMD should be evaluated with advanced imaging to rule out occult pathology. PMID- 22307773 TI - Very high levels of anti-citrullinated protein antibodies are associated with HLA DRB1*15 non-shared epitope allele in patients with rheumatoid arthritis. AB - OBJECTIVE: Production of anti-citrullinated protein antibodies (ACPAs) is an important biomarker for rheumatoid arthritis (RA). We undertook this study to determine whether genetic factors (HLA-DRB1 alleles) are associated with extreme ACPA levels in individuals with ACPA-positive RA, and to ascertain whether there are any phenotypic characteristics associated with these subgroups of RA. METHODS: HLA-DRB1 allelic groups were genotyped in 1,073 ACPA-positive RA patients from the Swedish Epidemiological Investigation of Rheumatoid Arthritis study. We found that 283 patients (26.4%) had high ACPA levels (defined as >1,500 units/ml using the Euro-Diagnostica anti-CCP2 test), while the rest of the patients had moderate ACPA levels and served as the comparison group. A replication group consisted of 235 RA patients. RESULTS: No significant differences in baseline disease activity were observed between patients with high and those with moderate ACPA levels. However, the HLA-DRB1*15 allele was associated with high ACPA levels (P=0.0002). A similar trend was detected in HLA DRB1*15-positive patients in the replication cohort, with meta-analysis of the discovery and replication cohorts demonstrating an overall effect of HLA-DRB1*15 on development of high ACPA levels in both the discovery and replication cohorts (P<0.0001 by Mantel-Haenszel test with a fixed-effects model). CONCLUSION: Our data indicate that HLA-DRB1*15 may promote the production of high ACPA levels. Due to the high value of ACPA level scores in the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA, the presence of HLA-DRB1*15 may, at least in part, contribute to fulfilling the criteria for RA. This illustrates the complex nature of the genetic regulation of ACPA levels. Additional mechanistic studies of the regulation of ACPAs and ACPA positive RA are pending. PMID- 22307775 TI - Polymorphisms in the VEGF-A in polypoidal choroidal vasculopathy in a Korean population. AB - PURPOSE: The aim of this study was to investigate whether polymorphisms in the vascular endothelial growth factor A gene (VEGF-A) are associated with polypoidal choroidal vasculopathy (PCV) in a Korean population and whether they are associated with PCV phenotypes. METHODS: This was a case-control study comprising 111 patients with PCV and 123 control participants. The PCV and control groups were genotyped for five polymorphisms in VEGF-A. Clinical characteristics were evaluated, including best-corrected visual acuity, fundus findings, and angiography findings at the first visit. Main outcome measures were the genotypes of variants and association with phenotypes. RESULTS: Only rs833069 in VEGF-A generated significant allelic associations with PCV (P = 2.24 * 10(-5)). As compared with the AA group, the GG genotype group in rs833069 had a 6.25-fold increased risk of PCV [P = 7.45 * 10(-5), 95% confidence interval (CI) 2.52 15.46] and the AG group had a 1.82-fold increased risk (P = 0.029, 95% CI 1.03 3.24). The haplotype CCGC in VEGF-A showed an association with PCV (P = 2.90 * 10(-5)). However, the phenotypic characteristics of PCV did not show an association with the rs833069 genotypes. CONCLUSIONS: The rs833069 polymorphism in VEGF-A was significantly associated with the risk of PCV in a Korean population. PMID- 22307776 TI - Dynamics of expression patterns of AQP4, dystroglycan, agrin and matrix metalloproteinases in human glioblastoma. AB - In human glioblastoma, the blood-brain barrier (BBB) is disturbed. According to our concept, the glio-vascular relationships and thus the control of the BBB are essentially dependent on the polarity of astroglial cells. This polarity is characterized by the uneven distribution of the water channel protein aquaporin-4 (AQP4), dystroglycan and other molecules. Recently, we were able to show that the extracellular matrix component agrin is important for the construction and localization of the so-called orthogonal arrays of particles (OAPs), which consist in AQP4. Here, combining freeze-fracture electron microscopy, immunohistochemistry and Western blotting, we describe alterations of expression and distribution of AQP4, dystroglycan, agrin and the matrix metalloproteinases (MMP) 2, 3 and 9 in human primary glioblastomas (eight primary tumours, six recurrent tumours). Increase of MMP3- and MMP2/9 immunoreactivities went along with loss of agrin and dystroglycan respectively. On the protein level, AQP4 expression was increased in glioblastoma compared to control tissue. This was not accompanied by an increase of OAPs, suggesting that AQP4 can also occur without forming OAPs. The results underline our concept of the loss of glioma cell polarity as one of the factors responsible for the disturbance of the neurovascular unit and as an explanation for the formation of edemas in the glioblastoma. PMID- 22307777 TI - The middle-class nature of identity and its implications for education: a genealogical analysis and reevaluation of a culturally and historically bounded concept. AB - We consider identity as a historically emerging discourse that requires genealogical analysis - not to discover the roots of our identity but to commit [ourselves] to its dissipation (Foucault 1977, p. 162). We suggest analyzing identity through the history of socio-economic classes, their life struggles, ambitions, development, and reproduction. We see learning not as a project of transformation of identity, but rather as developing access to socially valuable practices and developing one's own voice within these practices (through addressing and responding to other voices). The access and voice projects free agents from unnecessary finalization and objectivization by oneself and others (Bakhtin 1999; Bakhtin 1990). In education, we should develop indigenous discourses of learning and develop a conceptual framework that makes analysis of diverse discourses possible. We argue that learning, as transformation of participation in a sociocultural practice to gain more access, is a better conceptual framework than learning as transformation of identity. PMID- 22307778 TI - Treatment of hemophagocytic lymphohistiocytosis with cyclophosphamide, vincristine, and prednisone. AB - The goal of this study was to observe the therapeutic efficacy of cyclophosphamide, vincristine and prednisone combined chemotherapy (COP) in treating adult haemophagocytic lymphohistiocytosis (HLH). Fifteen cases diagnosed with HLH were enrolled in our study. Each of them was treated with the COP regimen. Two of the fifteen patients had autoimmune disease-associated HLH (13.3%), 2/15 had lymphoma-associated HLH (13.3%), 7/15 had infection-associated HLH (IAHLH) (46.7%), and the remaining 4/15 developed the disease in the absence of apparent underlying disease (26.7%). A complete response (CR) was achieved in 7/15 patients (46.7%), while a partial response (PR) was achieved in 5/15 patients (33.3%). With a mean follow-up of 72.5 weeks, the one-year overall survival was 66.7%. HLH of varying aetiology exhibited differing sensitivity and response to the COP regimen. In combination with aetiological and supportive treatment, the COP regimen as a mild and cost-effective chemotherapy is especially favourable for IAHLH, autoimmune disease-associated HLH, and disease severity precluding intensive treatment. PMID- 22307779 TI - Directed electron transfer in Langmuir-Schafer layers of porphyrin-fullerene and phthalocyanine-fullerene dyads in inverted organic solar cells. AB - In this study double linked porphyrin-fullerene and phthalocyanine-fullerene dyads and a single linked phthalocyanine-fullerene dyad were studied as components in inverted organic solar cells (OSCs) equipped with the well known P3HT:PCBM bulk heterojunction as the photoactive layer. The dyad monolayers were deposited onto a surface of P3HT:PCBM by using the Langmuir-Schafer method, therefore forming oriented monolayers in which the electron donor (D) and the acceptor (A) exist as a close proximity pair in a 1:1 molar ratio. As a result of this structure short circuit current density (J(sc)), open circuit voltage (V(oc)), and power conversion efficiency (eta) increased, while the fill factor (FF) remained the same. The devices which contained dyads with double linkage produced higher efficiencies than the one with a single linked dyad. This result can be explained in terms of molecular orientation. It was also verified that the prepared OSC devices have promising long term air stability. PMID- 22307780 TI - Plant molecular pharming 2012 and beyond. PMID- 22307781 TI - Cloning and characterization of the stress-induced bZIP gene ZmbZIP60 from maize. AB - ZmbZIP60 is a member of the bZIP transcription factor family in maize. Expression of ZmbZIP60 is strongly induced by a wide spectrum of stresses, including dehydration, high salinity, abscisic acid and tunicamycin treatments. A truncated form of ZmbZIP60, without a transmembrane domain (ZmbZIP60DeltaC) and fused with GFP, is localized in the nucleus, suggesting the translocation of the native protein to the nucleus by release from the membrane. Yeast one-hybrid analysis showed that both ZmbZIP60 and ZmbZIP60DeltaC had transcriptional activity. The expression of ZmbZIP60 in Arabidopsis bzip60 mutant partially restored the induction of BiP3 transcription under TM treatment, which indicated that ZmbZIP60 may play a role in the signal transduction of endoplasmic reticulum stress. Overexpression of ZmbZIP60 in wild-type Arabidopsis displayed enhanced bolting trends when subjected to dithiothreitol stress. Real-time PCR analysis revealed that some key genes in floral transition, including CO, FT, and AP1, were up- or down-regulated in ZmbZIP60-overexpressing plants, which may reveal the functional difference of ZmbZIP60 from AtbZIP60. PMID- 22307782 TI - Differential expression of genes involved in alternative glycolytic pathways, phosphorus scavenging and recycling in response to aluminum and phosphorus interactions in Citrus roots. AB - The objective was to determine the possible links between the expression levels of genes involved in alternative glycolytic pathways, phosphorus (P) scavenging and recycling and Citrus tolerance to aluminum (Al) and/or P-deficiency. 'Xuegan' (Citrus sinensis) and 'Sour pummelo' (Citrus grandis) seedlings were irrigated for 18 weeks with nutrient solution containing 0 and 1.2 mM AlCl(3).6H(2)O * 0, 50 and 200 MUM KH(2)PO(4). C. sinensis displayed more tolerant to Al and P deficiency than C. grandis. Under Al stress, C. sinensis accumulated more Al in roots and less Al in shoots than C. grandis. P concentration was higher in C. sinensis shoots and roots than in C. grandis ones. C. sinensis roots secreted more malate and citrate than C. grandis ones when exposed to Al. Al-induced secretion of malate and citrate by excised roots from Al-treated seedlings decreased with increasing P supply. Al-induced-secretion of malate and citrate from roots and Al precipitation by P in roots might be responsible for Al tolerance of C. sinensis. qRT-PCR analysis showed that Al-activated malate transporter (ALMT1), ATP-dependent phosphofructokinase (ATP-PFK), pyrophosphate dependent phosphofructokinase (PPi-PFK), tonoplast adenosine-triphosphatase subunit A (V-ATPase A), tonoplast pyrophosphatase (V-PPiase), pyruvate kinase (PK), acid phosphatase (APase), phosphoenolpyruvate carboxylase (PEPC), malic enzyme (ME) and malate dehydrogenase (MDH) genes might contribute to the tolerance of Citrus to Al and/or P-deficiency, but any single gene could not explain the differences between the two species. Citrus tolerance to Al and/or P deficiency might be caused by the coordinated regulation of gene expression involved in alternative glycolytic pathways, P scavenging and recycling. PMID- 22307783 TI - Simple technique for RNA purification from mouse inner ear hair cells. AB - Obtaining a good quality of RNA from small population of cells remain an issue. Isolation for a special anatomic location such as inner ear placed in the temporal bone become a challenge, especially in terms of time needed for isolation of living tissue from the bone, which is a key factor to preserve the RNA. Due to limited accessibility to the technologies such as laser dissection, we present a simplified procedure for isolation of good quality of RNA from the inner ear for further studies. PMID- 22307784 TI - The sex-specific association of Met62Ile gene polymorphism in P-selectin glycoprotein ligand (PSGL-1) with carotid plaque presence: preliminary study. AB - Atherosclerosis is known as an inflammatory disease in which a recruitment of leukocytes to the endothelium wall represents a preliminary step of the initiation and the development of disease. The P-selectin glycoprotein ligand (PSGL-1) seems to be the major molecule mediating leukocyte-endothelium interactions and leukocyte rolling on stimulated endothelium. There are limited number of studies reporting on association of Met62Ile SNP in PSGL-1 gene and the risk for atherosclerosis. The aim of this study was to analyze possible association of this polymorphism with an advanced carotid atherosclerosis and biochemical markers of inflammation and haemostasis. The 275 patients consecutively admitted for carotid endarterectomy with stenosis >70% and 256 controls of the same ethnic origin were included in the study. The Met62Ile genotypes were determined by PCR RFLP. The Ile/Ile homozygotes had significantly higher CRP compared to the other genotypes in patients. Female patients had Ile allele dose-dependent association with the carotid plaque presence (Met/Met vs. Met/Ile vs. Ile/Ile; OR 1, OR 2.02, CI 1.0-4.08, OR 4.08, CI 1.0-16.81, respectively, p = 0.04). Our results suggest the impact of PSGL-1 Met62Ile polymorphism on inflammation in advanced atherosclerosis. We observed the sex differential association of Met62Ile with advanced carotid atherosclerosis. Studies in larger and different populations should validate and further examine the suggested role of genetic variations in PSGL-1 with atherosclerosis and thrombosis. PMID- 22307785 TI - Analysis of the genetic diversity of physic nut, Jatropha curcas L. accessions using RAPD markers. AB - A sum of 48 accessions of physic nut, Jatropha curcas L. were analyzed to determine the genetic diversity and association between geographical origin using RAPD-PCR markers. Eight primers generated a total of 92 fragments with an average of 11.5 amplicons per primer. Polymorphism percentages of J. curcas accessions for Selangor, Kelantan, and Terengganu states were 80.4, 50.0, and 58.7%, respectively, with an average of 63.04%. Jaccard's genetic similarity co efficient indicated the high level of genetic variation among the accessions which ranged between 0.06 and 0.81. According to UPGMA dendrogram, 48 J. curcas accessions were grouped into four major clusters at coefficient level 0.3 and accessions from same and near states or regions were found to be grouped together according to their geographical origin. Coefficient of genetic differentiation (G(st)) value of J. curcas revealed that it is an outcrossing species. PMID- 22307786 TI - Molecular cloning and characterization of a novel RING zinc-finger protein gene up-regulated under in vitro salt stress in cassava. AB - Cassava (Manihot esculenta Crantz) is one of the world's most important food crops. It is cultivated mainly in developing countries of tropics, since its root is a major source of calories for low-income people due to its high productivity and resistance to many abiotic and biotic factors. A previous study has identified a partial cDNA sequence coding for a putative RING zinc finger in cassava storage root. The RING zinc finger protein is a specialized type of zinc finger protein found in many organisms. Here, we isolated the full-length cDNA sequence coding for M. esculenta RZF (MeRZF) protein by a combination of 5' and 3' RACE assays. BLAST analysis showed that its deduced amino acid sequence has a high level of similarity to plant proteins of RZF family. MeRZF protein contains a signature sequence motif for a RING zinc finger at its C-terminal region. In addition, this protein showed a histidine residue at the fifth coordination site, likely belonging to the RING-H2 subgroup, as confirmed by our phylogenetic analysis. There is also a transmembrane domain in its N-terminal region. Finally, semi-quantitative RT-PCR assays showed that MeRZF expression is increased in detached leaves treated with sodium chloride. Here, we report the first evidence of a RING zinc finger gene of cassava showing potential role in response to salt stress. PMID- 22307787 TI - Pooled-analysis of the associations between three polymorphisms in the VEGF gene and age-related macular degeneration. AB - The vascular endothelial growth factor (VEGF) gene has been suggested to play an important role in the pathogenesis of age-related macular degeneration (AMD). However, the results have been inconsistent. In this study, we performed a meta analysis to clarify the associations between VEGF polymorphisms and AMD risk across different populations. Published literature from PubMed and EMBASE were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Five studies (1,280 cases and 715 controls) for rs833061 polymorphism, five studies (1,033 cases and 807 controls) for rs1413711 polymorphism, and four studies (1,217 cases and 4,079 controls) for rs2010963 polymorphism were identified. No statistically significant association was found for rs833061, rs1413711 and rs2010963 polymorphisms, although there were significant associations for rs833061 polymorphism under a homogeneous co-dominant model (CC vs. TT: OR = 1.59, 95%CI 1.14-2.23) and for rs1413711 polymorphism under a recessive model (TT vs. CT + CC: OR = 1.50, 95%CI 1.08-2.08), the results were not robust by sensitivity analysis. However, there was a significant association for rs833061 among European and East Asian populations, and for rs1413711 among Europeans. The present meta-analyses indicated that there were no significantly associations between VEGF polymorphisms (rs833061, rs1413711, rs2010963) and the risk of AMD, although the association was different for each polymorphism among different populations. PMID- 22307788 TI - DNA microarray analysis reveals differential gene expression in the soleus muscle between male and female rats exposed to a high fat diet. AB - It is well recognized that diet-induced dysfunctions in skeletal muscle are closely related with many metabolic diseases, such as obesity and diabetes. In the present study, we identified global changes in gender-dependent gene expressions in the soleus muscle of lean and obese rats fed a high fat diet (HFD), using DNA microarray analysis. Prior to microarray analysis, the body weight gains were found to be higher in male HFD rats than the female HFD rats. To better understand the detailed phenotypic differences in response to HFD feeding, we identified differential gene expression in soleus muscle between the genders. To this end, we extracted and summarized the genes that were up- or down regulated more than 1.5-fold between the genders in the microarray data. As expected, a greater number of genes encoding myofibrillar proteins and glycolytic proteins were expressed higher in males than females when exposed to HFD, reflecting greater muscular activity and higher capacity for utilizing glucose as an energy fuel. However, a series of genes involved in oxidative metabolism and cellular defenses were more up-regulated in females than males. These results allowed us to conclude that compared to males, females have greater fat clearing capacity in skeletal muscle through the activation of genes encoding enzymes for fat oxidation. In conclusion, our microarray data provide a better understanding of the molecular events underlying gender dimorphism in soleus muscle, and will provide valuable information in improving gender awareness in the health care system. PMID- 22307789 TI - Effect of active immunization against a recombinant mouse granulocyte-macrophage colony-stimulating factor/somatostatin fusion protein on the growth of mice. AB - Female BALB/c mice were actively immunized subcutaneously with a recombinant protein of granulocyte-macrophage colony-stimulating factor (GM-CSF) fused with somatostatin (SS) (GM-CSF/SS). Fifty-four days after the primary immunization, the body weight of the immunized mice increased by 4.62% compared with the control (P < 0.05), together with the induction of detectable serum antibodies against SS. The level of serum growth hormone (GH) elevated by 44.54% (P < 0.05) and the mRNA expression of muscular IGF-1 increased by 94% for the GM-CSF/SS treated mice. The results indicated that the recombinant protein GM-CSF/SS was efficient in inducing specific immunity against SS, subsequently leading to the increase of the GH level by SS neutralization, and ultimately improving the growth of mice. PMID- 22307790 TI - Association of the interleukin-10 1082G/A, 819C/T and 3575T/A gene polymorphisms with systemic sclerosis: a meta-analysis. AB - Many environmental and genetic factors have been contributed to the development of systemic sclerosis (SSc). To determine whether IL-10 gene polymorphisms are associated with SSc, we conducted a meta-analysis approach. A total of eight studies involving 1,034 SSc cases and 1,815 controls were obtained by electronic database, i.e. Embase, Blackwell, Scopus, China National Knowledge Infrastructure database, Chinese Biomedical database, Google searching. We analyzed three gene polymorphisms, including IL-10 -1082G/A (rs1800896), IL-10 -819C/T (rs1800871), IL-10 -3575T/A (rs1800890). The combined odds ratio (OR) with its 95% confidence interval (95% CI) was calculated using fixed or random effect models. We found that IL-10 819C allele might contribute to SSc susceptibility by fixed effect model and IL-10 3575A allele could be an important risk factor for SSc, especially in European descent. No significant heterogeneity were observed. Under random effect model, there was no evidence of statistically significant association between IL-10 1082G/A polymorphism and SSc. Publication bias was absent in all analyses. However, larger scale primary studies are required to further evaluate the IL-10 polymorphism and SSc. PMID- 22307791 TI - AIB1 polymorphisms with breast cancer susceptibility: a pooled analysis of variation in BRCA1/2 mutation carriers and non-carriers. AB - The AIB1 gene (amplified in breast cancer 1), coding for a member of steroid receptor co-activator p160 protein family is involved in regulation of estrogen receptor transactivation influencing the estrogen-dependent gene expression. It contains a glutamine repeat polymorphism and several single nucleotide polymorphisms that may alter the transcriptional activation of the receptor and affect susceptibility to breast cancer. Previous studies have shown that these polymorphisms may modify the breast cancer risk in women carrying BRCA1/2 mutations. However, the results remained controversial. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship. A total of 22 studies were identified, including 3,742 cases and 3,491 controls for AIB1 polyglutamine repeat polymorphism, 2,170 cases and 3,309 controls for Q586H polymorphism, and 2,183 cases and 3,319 controls for T960T polymorphism. Overall, we found no evidence of association for individuals who carried at least one AIB1 allele of 28 or 29 or more repeat with breast cancer risk. But we found increased breast cancer risk in BRCA1/2 mutation carriers for individuals with both alleles >=29 polyglutamine repeat (OR, 1.64; 95% CI 1.24 2.17). And reduced risk was found to be associated with the Q586H polymorphism among the variant homozygote genotype carriers (OR, 0.42; 95% CI 0.23-0.77). Our results do not support the direct association of AIB1 polyglutamine repeat length and breast cancer. However, we found that BRCA1/2 mutation carriers with both alleles >=29 repeats have a higher risk of breast cancer. PMID- 22307792 TI - A mini review on the antimicrobial peptides isolated from the genus Hylarana (Amphibia: Anura) with a proposed nomenclature for amphibian skin peptides. AB - Hylarana is a well established frog genus coming under the family Ranidae. An increasing number of antimicrobial peptides have been isolated and characterized from the skin of frogs of this genus. This review covers the antimicrobial peptides reported so far from the frogs of Hylarana genus and to propose a consistent system of nomenclature for amphibian skin peptides. Multiple sequence alignment of the skin peptides from Hylarana genus has grouped them into six peptide families, and three bioactive peptides. Existing nomenclature of amphibian antimicrobial peptides is species centered with no implication to the genus which can lead to disparities, when frogs with same species name belonging to different genus have to be named. As per the proposed system the peptide should have the parent peptide name (e.g. Brevinin-1) followed by two uppercase letter of the genus, if two genera begin with the same letter-first letter should be the same followed by an appropriate second letter (e.g. HU for Huia and HM for Humenerana). This is succeeded by species name in lower case-orthologous peptides from different species may be characterized by the initial letter of that species, when two species begin with the same initial letter, second letter should be used appropriately (e.g. HLat for Hylarana aurata and HLan for Hylarana aurantiaca). Paralogs belonging to the same peptide family are assigned by numbers. PMID- 22307793 TI - Characterization of a spliced variant of human IRF-3 promoter and its regulation by the transcription factor Sp1. AB - Interferon regulatory factor 3 (IRF-3), an essential transcriptional regulator of the interferon genes, plays an important role in host defense against viral and microbial infection as well as in cell growth regulation. Promoter plays a crucial role in gene transcription. We have reported the characterization of the wide type of human IRF-3 promoter, but the characterization of the spliced variant of human IRF-3 Int2V1 promoter has not been systematically analyzed. To observe the spliced variant of human IRF-3 promoter, we have cloned the human IRF 3 gene promoter region containing 300 nucleotides upstream the transcription start site (TSS). Transient transfection of 5' deleted promoter-reporter constructs and luciferase assay illustrated the region -159/-100 relative to the TSS is sufficient for full promoter activity. This region contains GATA1 and specific protein-1 (Sp1) transcription factor binding sites. Interestingly, mutation of this Sp1 site reduced the promoter activity by 50%. However, overexpression of Sp1 increased the transcription activity by 2.4-fold. These results indicated that the spliced variant of human IRF-3 gene core promoter was located within the region -159/-100 relative to the TSS. Sp1 transcription factor upregulates the spliced variant of human IRF-3 gene promoter. PMID- 22307794 TI - Association of TLR4 polymorphism with cytokine expression level and pulmonary lesion score in pigs. AB - The toll-like receptor 4 (TLR4), recognizing lipopolysaccharide of gram-negative bacteria, plays an essential role in immune responses. Variation in TLR4 alters host immune responses to pathogen and is associated with resistance/susceptibility to infectious diseases, as suggested by studies in humans and agricultural species, including cattle and chicken. In this study, we analyzed association of single nucleotide polymorphisms (SNPs) of TLR4 with cytokine expression level and pulmonary lesion score in swine. The SNP c.611 T>A showed significant association with the transcription levels of IFNG, TNFA, and IL-6 (P < 0.05); the SNP c.962 G>A showed significant association with the transcription of IFNG, IL-2, and IL-4 (P < 0.05); the SNP c.1,027 C>A showed significant association with the transcription of IFNG and IL-6 (P < 0.05); the haplotypes showed significant association with the transcription of IFNG, IL-2, IL-4, IL-6, and TNFA (P < 0.05). Both SNPs c.611 T>A and c.962 G>A showed significant association with pulmonary lesion scores (P < 0.01); and the combination genotypes of 3 polymorphic sites were also significantly associated with pulmonary lesion scores (P < 0.01). The observed relationship between TLR4 polymorphism and the transcription levels of cytokines indicate that these SNPs are related to the modulation of the cytokine mediated immune response. PMID- 22307795 TI - Rapid identification of Enterococcus faecalis by species-specific primers based on the genes involved in the Entner-Doudoroff pathway. AB - In this study we report a novel method for identification of Enterococcus faecalis based on polymerase chain reaction with primers specific for the eda genes encoding the enzymes involved in the Entner-Doudoroff pathway, a pathway present only in this species among Gram-positive bacteria. The designed primers were checked in several different Enterococcus species, and with some other Gram positive and Gram-negative bacterial species as well. Five primer combinations were used to detect the eda-1 gene, and another three for the eda-2 gene. With the exception of one of the primer combinations, all the others gave as results the expected amplification products only in E. faecalis strains. PMID- 22307796 TI - Degradation of mouse NTE-related esterase by macroautophagy and the proteasome. AB - NTE-related esterase (NRE) is a novel endoplasmic reticulum-anchored lysophospholipase with high homology to neuropathy target esterase (NTE). However, little is known about the regulation of NRE protein. In the current study, we investigated the degradation pathways of mouse NRE (mNRE) in mammalian cells. Based on experiments with inhibitors and inducer of protein degradation pathways, we provide here the first evidence that mNRE is degraded by macroautophagy as well as by the proteasome. Moreover, the contribution of protein domains to the degradation of mNRE was investigated, which showed that the transmembrane and regulatory domain played a role in the degradation of mNRE by macroautophagy and the proteasome respectively. In contrast the C-terminal catalytic domain was not involved in both degradation pathways of mNRE. These findings showed for the first time that the degradation pathways in controlling mNRE quantity and may provide further insight into structure and regulation of mNRE. PMID- 22307797 TI - Nucleotide diversity of the melanocortin 1 receptor gene (MC1R) in the gayal (Bos frontalis). AB - The melanocortin 1 receptor gene (MC1R) plays a crucial role in determining coat colour of mammals. To investigate the relationship of polymorphism of the MC1R with coat colour in gayal, the coding sequence (CDS), and the 5'- and 3' untranslated regions (UTR) of the MC1R were sequenced from 63 samples from the gayal and compared with the sequences of the MC1R from other ruminant species. A sequence of 1,136 bp including the whole CDS (954 bp) and parts of the 5'- and 3' UTR (164 and 18 bp, respectively) of the gayal MC1R was obtained. A total of nine single nucleotide polymorphisms (SNPs) including four SNPs (c.-129T>C, c.-127A>C, c.-106C>T, c.-1G>A) in the 5'-UTR and five SNPs (c.201C>T, c.583C>T, c.663T>C, c.871A>G and c.876T>C) in the CDS were detected, revealing high genetic diversity. Three novel coding SNPs including c.201C>T, c.583C>T and c.876T>C, which have not been reported previously in bovid species, were retrieved. Within five coding SNPs, c.201C>T, c.663T>C and c.876T>C were silent mutations, while c.583C>T and c.871A>G were mis-sense mutations, resulting in changes in the amino acids located in the fifth (p.L195F) and seventh (p.T291A) transmembrane regions, respectively. The alignment of amino acid sequences was found to be very similar to those for other bovid species. It was demonstrated, using the functional effect prediction, that the p.T291A amino acid replacement could have an effect on MC1R protein function but not for the p.L195F substitution. Using phylogenetic analyses it was revealed that the gayal has a close genetic relationship with the yak. However, three classical bovine MC1R loci the E (D), E (+) and e were not retrieved in the gayal, indicating other genes or factors could affect coat colour in this species. PMID- 22307798 TI - Interrelationship between calmodulin (CaM) and H2O2 in abscisic acid-induced antioxidant defense in the seedlings of Panax ginseng. AB - Calmodulin (CaM), the predominant Ca(2+) receptors, is one of the best characterized Ca(2+) sensors in all eukaryotes. In this study the role of CaM and the possible interrelationship between CaM and hydrogen peroxide (H(2)O(2)) in abscisic acid (ABA) induced antioxidant defense were investigated in the seedling of Panax ginseng. Treatment of ABA (100 MUM) and H(2)O(2) (10 mM) increased the expression of Panax ginseng calmodulin gene (PgCaM) and significantly enhanced the expression of the antioxidant marker genes such as superoxide dismutase, ascorbate peroxidase, glutathione reductase and the activities of chloroplastic and cytosolic antioxidant enzymes. Pretreatments with two CaM antagonists, trifluoperazine (TFP), N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide hydrochloride (W7) and inhibitor or scavenger, diphenyleneiodonium chloride, and dimethylthiourea of reactive oxygen species almost completely suppressed the up regulation of antioxidant and PgCaM gene. Moreover, H(2)O(2) production and CaM content was almost completely inhibited by pretreatments with two CaM antagonists. In addition, the expressions of PgCaM gene under different biotic stress were analyzed at different time intervals. Thus it may suggests that CaM are involved in ABA-induced increased expression of PgCaM which triggers H(2)O(2) production through activating trans-plasma membrane NADPH oxidase, resulting in up-regulation of defense related antioxidant gene and also plays a pivotal role in defense response against pathogens. PMID- 22307802 TI - Amine synthesis through mild catalytic hydrosilylation of imines using polymethylhydroxysiloxane and [RuCl2(arene)]2 catalysts. PMID- 22307799 TI - An inherited disorder with splenomegaly, cytopenias, and vision loss. AB - We describe a novel inherited disorder consisting of idiopathic massive splenomegaly, cytopenias, anhidrosis, chronic optic nerve edema, and vision loss. This disorder involves three affected patients in a single non-consanguineous Caucasian family, a mother and two daughters, who are half-sisters. All three patients have had splenectomies; histopathology revealed congestion of the red pulp, but otherwise no abnormalities. Electron microscopic studies of splenic tissue showed no evidence for a storage disorder or other ultrastructural abnormality. Two of the three patients had bone marrow examinations that were non diagnostic. All three patients developed progressive vision loss such that the two oldest patients are now blind, possibly due to a cone-rod dystrophy. Characteristics of vision loss in this family include early chronic optic nerve edema, and progressive vision loss, particularly central and color vision. Despite numerous medical and ophthalmic evaluations, no diagnosis has been discovered. PMID- 22307803 TI - Serial suture ligation glossectomy for squamous cell carcinoma in the setting of a massive lymphovascular malformation. AB - BACKGROUND: We describe a novel surgical technique for resection of squamous cell carcinoma in the setting of a massive tongue lymphovascular malformation (LVM). METHODS AND RESULTS: A 75-year-old man with a history of long-standing massive LVM of the tongue presented with a 4-cm squamous cell carcinoma of the involved oral tongue. Given the aberrant vascular anatomy of this lesion, traditional surgical treatment could not be undertaken. Therefore, serial suture ligation was performed over a 2-week period, allowing complete excision of the squamous cell carcinoma and a large portion of the tongue LVM with minimal morbidity. Return to preoperative functional status was likewise achieved. CONCLUSION: Serial suture ligation glossectomy is a simple and effective technique for treating the uncommon case of squamous cell carcinoma of the tongue in the setting of a massive LVM. PMID- 22307804 TI - Involvement of non-vascular stem cells in blood vessel formation. AB - Blood vessels clearly act as conduits for blood flow, but recently the concept that they are also involved in organ maintenance, especially by providing a niche for organ-specific stem cells, has begun to emerge. Moreover, several lines of evidence suggest that hematopoietic stem cells can differentiate directly into cells composing blood vessels. Recently, cancer stem cells (CSCs) have also been assigned these roles in the cancer microenvironment. Although anti-angiogenic drugs have been developed and are utilized in the clinic for their anti-tumor activity, their suppressive effects on tumor growth have been disappointing. This may be caused by transferring drug resistance from CSCs to endothelial cells. It has been suggested that CSCs localize in the peri-vascular niche. Therefore, it is extremely important to know how the vascular niche maintains CSCs, as such knowledge may enable us to develop promising new approaches to cancer treatment. PMID- 22307805 TI - Prospective cohort study of radiotherapy with concomitant and adjuvant temozolomide chemotherapy for glioblastoma patients with no or minimal residual enhancing tumor load after surgery. AB - Survival of glioblastoma patients has been linked to the completeness of surgical resection. Available data, however, were generated with adjuvant radiotherapy. Data confirming that extensive cytoreduction remains beneficial to patients treated with the current standard, concomitant temozolomide radiochemotherapy, are limited. We therefore analyzed the efficacy of radiochemotherapy for patients with little or no residual tumor after surgery. In this prospective, non interventional multicenter cohort study, entry criteria were histological diagnosis of glioblastoma, small enhancing or no residual tumor on post-operative MRI, and intended temozolomide radiochemotherapy. The primary study objective was progression-free survival; secondary study objectives were survival and toxicity. Furthermore, the prognostic value of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation was investigated in a subgroup of patients. One hundred and eighty patients were enrolled. Fourteen were excluded by patient request or failure to initiate radiochemotherapy. Twenty-three patients had non evaluable post-operative imaging. Thus, 143 patients qualified for analysis, with 107 patients having residual tumor diameters <=1.5 cm. Median follow-up was 24.0 months. Median survival or patients without residual enhancing tumor exceeded the follow-up period. Median survival was 16.9 months for 32 patients with residual tumor diameters >0 to <=1.5 cm (95% CI: 13.3-20.5, p = 0.039), and 13.9 months (10.3-17.5, overall p < 0.001) for 36 patients with residual tumor diameters >1.5 cm. Patient age at diagnosis and extent of resection were independently associated with survival. Patients with MGMT promoter methylated tumors and complete resection made the best prognosis. Completeness of resection acts synergistically with concomitant and adjuvant radiochemotherapy, especially in patients with MGMT promoter methylation. PMID- 22307806 TI - Key elements in assessing the educational environment: where is the theory? AB - The educational environment has been increasingly acknowledged as vital for high quality medical education. As a result, several instruments have been developed to measure medical educational environment quality. However, there appears to be no consensus about which concepts should be measured. The absence of a theoretical framework may explain this lack of consensus. Therefore, we aimed to (1) find a comprehensive theoretical framework defining the essential concepts, and (2) test its applicability. An initial review of the medical educational environment literature indicated that such frameworks are lacking. Therefore, we chose an alternative approach to lead us to relevant frameworks from outside the medical educational field; that is, we applied a snowballing technique to find educational environment instruments used to build the contents of the medical ones and investigated their theoretical underpinnings (Study 1). We found two frameworks, one of which was described as incomplete and one of which defines three domains as the key elements of human environments (personal development/goal direction, relationships, and system maintenance and system change) and has been validated in different contexts. To test its applicability, we investigated whether the items of nine medical educational environment instruments could be mapped unto the framework (Study 2). Of 374 items, 94% could: 256 (68%) pertained to a single domain, 94 (25%) to more than one domain. In our context, these domains were found to concern goal orientation, relationships and organization/regulation. We conclude that this framework is applicable and comprehensive, and recommend using it as theoretical underpinning for medical educational environment measures. PMID- 22307807 TI - Lipase-catalyzed remote kinetic resolution of citalopram intermediate by asymmetric alcoholysis and thermodynamic analysis. AB - Lipase-catalyzed remote resolution of the tertiary alcohol, citalopram intermediate (diol acetate), has been achieved. The chiral discrimination was obtained by the Novozym435-catalyzed alcoholysis of the primary hydroxyl ester which was four bonds away from the center. The influence of acyl acceptor structure and the organic solvents on the reaction rate and enantioselectivity were investigated. Based on the thermodynamic analysis, the difference of activation free energy between the two enantiomers which dominated the enantioselectivity was significantly affected by the organic solvents, while the acyl acceptor showed less effect. In addition, the enantiomer discrimination was driven by both the difference of activation enthalpy and activation entropy. The thermodynamic analysis provides further insights into the prediction and optimization of enantioselectivity and reaction rate in remote resolution. PMID- 22307808 TI - Fermentation and evaluation of Klebsiella pneumoniae and K. oxytoca on the production of 2,3-butanediol. AB - Klebsiella is one of the genera that has shown unbeatable production performance of 2,3-butanediol (2,3-BD), when compared to other microorganisms. In this study, two Klebsiella strains, K. pneumoniae (DSM 2026) and K. oxytoca (ATCC 43863), were selected and evaluated for 2,3-BD production by batch and fed-batch fermentations using glucose as a carbon source. Those strains' morphologies, particularly their capsular structures, were analyzed by scanning electron microscopy (SEM). The maximum titers of 2,3-BD by K. pneumoniae and K. oxytoca during 10 h batch fermentation were 17.6 and 10.9 g L(-1), respectively; in fed batch cultivation, the strains showed the maximum titers of 50.9 and 34.1 g L( 1), respectively. Although K. pneumoniae showed higher productivity, SEM showed that it secreted large amounts of capsular polysaccharide, increasing pathogenicity and hindering the separation of cells from the fermentation broth during downstream processing. PMID- 22307809 TI - Novel glycoside of vanillyl alcohol, 4-hydroxy-3-methoxybenzyl-alpha-D glucopyranoside: study of enzymatic synthesis, in vitro digestion and antioxidant activity. AB - Novel glucoside of physiological active vanillyl alcohol was synthesized for the first time using maltase from Saccharomyces cerevisiae as catalyst, and established its structure as 4-hydroxy-3-methoxybenzyl-alpha-D: -glucopyranoside. The key reaction factors for this transglucosylation reaction were optimized using response surface methodology and the highest yield so far in maltase catalyzed transglucosylation reaction was obtained. It was found out that optimum temperature of reaction was 37 degrees C, optimal maltose concentration was 60% (w/v), optimal pH was 6.6, and optimal concentration of vanillyl alcohol was 158 mM. Under these conditions, yield of glucoside was 90 mM with no by product formation. It was shown that this compound posses good antioxidant activity as well as stability in gastrointestinal tract. It was demonstrated that it is hydrolyzed on brush border membrane of enterocytes, so it can serve in protecting gastrointestinal system from oxidation, as well as source of anticonvulsive drug after the hydrolysis of glucoside on brush border membrane of small intestine. PMID- 22307810 TI - Multifunctional lipid multilayer stamping. AB - Nanostructured lipid multilayers on surfaces are a promising biofunctional nanomaterial. For example, surface-supported lipid multilayer diffraction gratings with optical properties that depend on the microscale spacing of the grating lines and the nanometer thickness of the lipid multilayers have been fabricated previously by dip-pen nanolithography (DPN), with immediate applications as label-free biosensors. The innate biocompatibility of such gratings makes them promising as biological sensor elements, model cellular systems, and construction materials for nanotechnology. Here a method is described that combines the lateral patterning capabilities and scalability of microcontact printing with the topographical control of nanoimprint lithography and the multimaterial integration aspects of dip-pen nanolithography in order to create nanostructured lipid multilayer arrays. This approach is denoted multilayer stamping. The distinguishing characteristic of this method is that it allows control of the lipid multilayer thickness, which is a crucial nanoscale dimension that determines the optical properties of lipid multilayer nanostructures. The ability to integrate multiple lipid materials on the same surface is also demonstrated by multi-ink spotting onto a polydimethoxysilane stamp, as well as higher-throughput patterning (on the order of 2 cm(2) s(-1) for grating fabrication) and the ability to pattern lipid materials that could not previously be patterned with high resolution by lipid DPN, for example, the gel-phase phospholipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or the steroid cholesterol. PMID- 22307811 TI - Eosinophilic esophagitis: rapidly emerging disorder. AB - Eosinophilic Esophagitis (EoE), first described in the early 1990's, has rapidly evolved as distinctive chronic inflammatory esophageal disease. The diagnosis is based clinically by the presence of symptoms related to an esophageal dysfunction and histologically by an eosinophil-predominant inflammation once other conditions leading to esophageal eosinophilia are excluded. This striking male prevalent disease has an increasing incidence and prevalence in the westernised countries. Currently, EoE represents the main cause of dysphagia and bolus impaction in adult patients. Despite the fact that EoE often occurs in atopic patients, the value of allergic testing is still under discussion. Topical corticosteroids lead to a rapid improvement of active EoE clinically and histologically; they are therefore regarded as first-line drug therapy. Elimination diets have similar efficacy as topical corticosteroids, but their long-term use is limited by practical issues. Esophageal dilation of EoE-induced strictures can also be effective in improving symptoms, but this therapy has no effect on the underlying inflammation. Neither the diagnostic nor the long-term therapeutic strategies are yet fully defined. PMID- 22307813 TI - Associations of varus thrust and alignment with pain in knee osteoarthritis. AB - OBJECTIVE: To investigate associations of varus thrust and varus static alignment with pain in patients with knee osteoarthritis (OA). METHODS: This was a cross sectional study of participants from a randomized controlled trial of vitamin D treatment for knee OA. Participants were video recorded while walking and scored for presence of varus thrust. Static alignment was measured on standard posteroanterior knee radiographs. Pain questions from the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire were used to assess symptoms. We calculated means for total WOMAC pain in relation to varus thrust and static varus alignment (i.e., corrected anatomic alignment<178 degrees). Ordinal logistic regressions were performed, with responses on individual WOMAC pain questions as the outcomes and varus thrust and varus alignment as the predictors. RESULTS: There were 82 participants, 60% of whom were female. The mean+/-SD age was 65.1+/-8.5 years, and the mean+/-SD body mass index was 30.2+/-5.4 kg/m2. The mean total WOMAC pain score was 6.3 versus 3.9, respectively, in those with versus without definite varus thrust (P=0.007) and 5.0 versus 4.2 in those with versus without varus alignment (P=0.36). Odds ratios for pain with walking and standing were 4.7 (95% confidence interval 1.8-11.9) and 5.5 (95% confidence interval 2.2-14.2), respectively, in those with and those without definite varus thrust. There were no significant associations between varus alignment and responses to individual WOMAC pain questions. Sensitivity analyses suggested that varus classified using a more stringent definition might have been associated with pain on walking and standing. CONCLUSION: In patients with knee OA, varus thrust, and possibly varus static alignment, were associated with pain, specifically during weight-bearing activities. Treatment of varus thrust (e.g., via bracing or gait modification) may lead to improvement of symptoms. PMID- 22307814 TI - Metal artefact reduction in gemstone spectral imaging dual-energy CT with and without metal artefact reduction software. AB - OBJECTIVE: To assess the usefulness of gemstone spectral imaging (GSI) dual energy CT (DECT) with/without metal artefact reduction software (MARs). METHODS: The DECTs were performed using fast kV-switching GSI between 80 and 140 kV. The CT data were retro-reconstructed with/without MARs, by different displayed fields of-view (DFOV), and with synthesised monochromatic energy in the range 40-140 keV. A phantom study of size and CT numbers was performed in a titanium plate and a stainless steel plate. A clinical study was performed in 26 patients with metallic hardware. All images were retrospectively reviewed in terms of the visualisation of periprosthetic regions and the severity of beam-hardening artefacts by using a five-point scale. RESULTS: The GSI-MARs reconstruction can markedly reduce the metal-related artefacts, and the image quality was affected by the prosthesis composition and DFOV. The spectral CT numbers of the prosthesis and periprosthetic regions showed different patterns on stainless steel and titanium plates. CONCLUSION: Dual-energy CT with GSI-MARs can reduce metal related artefacts and improve the delineation of the prosthesis and periprosthetic region. We should be cautious when using GSI-MARs because the image quality was affected by the prosthesis composition, energy (in keV) and DFOV. The metallic composition and size should be considered in metallic imaging with GSI-MARs reconstruction. KEY POINTS: * Metal-related artefacts can be troublesome on musculoskeletal computed tomography (CT). * Gemstone spectral imaging (GSI) with dual-energy CT (DECT) offers a novel solution * GSI and metallic artefact reduction software (GSI-MAR) can markedly reduce these artefacts. * However image quality is influenced by the prosthesis composition and other parameters. * We should be aware about potential overcorrection when using GSI-MARs. PMID- 22307815 TI - Are intravenous injections of contrast media really less nephrotoxic than intra arterial injections? AB - We oppose the opinion that the intra-arterial administration of iodine-based contrast media (CM) appears to pose a greater risk of contrast medium-induced nephropathy (CIN) than intravenous administration since 1) in intra-arterial coronary procedures and most other intra-arterial angiographic examinations, CM injections are also intravenous relative to the kidneys, 2) there is a lack of comparative trials studying the risk of CIN between intra-arterial and intravenous procedures with matched risk factors and CM doses, 3) a bias selection of patients with fewer risk factors may explain the seemingly lower rate of CIN after CT in comparison with coronary interventions, 4) the rate of CIN following intra-arterial coronary procedures may also be exaggerated owing to other causes of acute kidney failure, such as haemodynamic instability and microembolisation, 5) roughly the same gram-iodine/GFR ratio (~1:1) as a limit of relatively safe CM doses has preliminarily been found for both intravenous CT and intra-arterial coronary procedures and 6) the substantially higher injected intravenous CM dose rate during CT relative to an intra-arterial coronary procedure might actually pose a higher risk of CIN following CT. KEY POINTS: * Most intra-arterial injections of contrast media are intravenous relative to the kidneys. * No evidence that intravenous CM injections should be less nephrotoxic than intra-arterial. * Considerably higher dose rates of CM are used for CT relative to intra-arterial procedures. * Higher dose rates may pose higher nephrotoxic risk for intravenous based CT studies. PMID- 22307816 TI - I148M PNPLA3 variant and progressive liver disease: A new paradigm in hepatology. PMID- 22307817 TI - Mouse forestomach carcinoma cells immunosuppress macrophages through transforming growth factor-beta1. AB - Peritoneal implantation metastasis of gastric cancer cells is associated with poor prognosis. Peritoneal macrophages are the most important immune cells in the abdominal cavity to control tumor metastasis. In the present study, the immunosuppressive effects of mouse forestomach cells on macrophages were examined. Conditioned medium from mouse forestomach cell cultures were used to treat isolated peritoneal macrophages. A colorimetry-based phagocytosis assay was performed to investigate the functional change of macrophages. The alteration of cytokine secretion by macrophages was measured by ELISA assay. Specific markers of macrophage polarization were analyzed by real-time RT-PCR. TGF-beta1 signaling was evaluated by western blotting. Neutralization experiments were performed using an anti-TGF-beta1 antibody. Conditioned medium reduced the phagocytotic capability of macrophages. Lower TNF-alpha and IL-1beta levels and higher IL-10 and VEGF levels were observed. Real-time RT-PCR showed increased mRNA levels of M2 macrophage markers. Further study revealed that TGF-beta1 was significantly elevated in the conditioned medium and TGF-beta1 signaling was activated in the macrophages by the treatment of conditioned medium. Neutralization of TGF-beta1 reversed the immunosuppressive effects on macrophages. Immunosuppressive macrophages can be induced by conditioned medium from mouse forestomach cell cultures. These effects appeared to occur through the production of TGF-beta1 by the tumor cells. Targeted TGF-beta1 intervention may help to control peritoneal metastasis of gastric cancers. PMID- 22307818 TI - Versatile effects of aurone structure on mushroom tyrosinase activity. AB - Elucidation of the binding modes of Ty inhibitors is an important step for in depth studies on how to regulate tyrosinase activity. In this paper we highlight the extraordinarily versatile effects of the aurone structure on mushroom Ty activity. Depending on the position of the OH group on the B-ring, aurones can behave either as substrates or as hyperbolic activators. The synthesis of a hybrid aurone through combination of an aurone moiety with HOPNO (2 hydroxypyridine N-oxide), a good metal chelate, led us to a new, efficient, mixed inhibitor for mushroom tyrosinase. Another important feature pointed out by our study is the presence of more than one site for aurone compounds on mushroom tyrosinase. Because study of the binding of the hybrid aurone was difficult to perform with the enzyme, we undertook binding studies with tyrosinase functional models in order to elucidate the binding mode (chelating vs. bridging) on a dicopper(II) center. Use of EPR combined with theoretical DFT calculations allowed us to propose a preferred chelating mode for the interaction of the hybrid aurone with a dicopper(II) center. PMID- 22307819 TI - Up-front neck dissection followed by concurrent chemoradiation in patients with regionally advanced head and neck cancer. AB - BACKGROUND: The appropriate management of the neck in patients with regionally advanced head and neck cancer remains controversial. The purpose of this study was to retrospectively analyze our institutional experience with up-front neck dissection followed by definitive chemoradiotherapy. METHODS: Fifty-five patients with radiographic evidence of large or necrotic lymph nodes underwent up-front neck dissection followed by definitive chemoradiation. RESULTS: The 5-year overall survival (OS) and progression-free survival (PFS) rates were estimated at 71.3% and 64.7%, respectively. There were 2 failures in the dissected neck, for a control rate of 96.7%. There were 7 locoregional failures and 12 distant failures, for locoregional and distant control rates of 87.3% and 78.2%, respectively. CONCLUSION: Up-front neck dissection followed by chemoradiotherapy resulted in excellent locoregional control, OS, and PFS. Utilization of this strategy should be considered in carefully selected patients with regionally advanced head and neck cancer. (c) 2012 Wiley Periodicals, Inc. Head Neck, 2012. PMID- 22307820 TI - No dose-no poison. PMID- 22307821 TI - The measurement of condom use in four countries in East and southern Africa. AB - Measurement of condom use is important to assess progress in increasing use. Since 2003, the Demographic and Health Surveys (DHS) and AIDS Indicator Surveys (AIS) have included new measures of self-reported condom use. We use data from Namibia, Swaziland, Tanzania, and Zambia to compare measures of condom use accounting for type of sexual partner. Condom use at last sex ranged from 20% in Tanzania to 57% in Namibia for men, and from 12% in Tanzania to 41% in Namibia for women. Reported condom use was lower in response to questions about condom use every time with last partner (from 13 to 47% for men and from 8 to 33% for women). Condom use was highest among people with two or more partners in the last year and lowest with marital partners. Overall, the prevalence of condom use was low, and there was wide variability across the various measures, countries, sexes, and types of partner. Promotion of condom use in all partnerships, but especially in non-marital relationships and among individuals with multiple partners, remains a critical strategy. New condom use questions in the DHS and AIS expand options for measuring and studying condom use. PMID- 22307822 TI - Tumors invading the cavernous sinus that cause internal carotid artery compression are rarely pituitary adenomas. AB - There is a clinical impression that when tumors invade the cavernous sinus, compression of the internal carotid artery is rare with pituitary adenomas and more common with other types of lesions but there are no actual data to support this impression. To confirm the impression that the finding of internal carotid artery compression by tumors invading the cavernous sinus is inconsistent with a diagnosis of a pituitary adenoma, we performed a retrospective analysis of MRI scans performed between 2000 and July 2009. An initial search of the radiology database was performed using the terms "invasive mass cavernous MRI" and subsequent refinement narrowed the evaluation to 141 patients with cavernous sinus invasion by sellar/parasellar tumors for whom there were clinical/pathological data to determine tumor type. 83 of the 141 patients with cavernous sinus invasion had carotid artery encasement; 58 were pituitary adenomas and 25 were other types of lesions. Eight of these 83 scans revealed compression of the internal carotid lumen, with only one being a pituitary adenoma and seven being other types of lesions. Therefore, only 1/58 (1.7%) of pituitary adenomas and 7/25 (28%) of non-pituitary adenoma lesions that encased the internal carotid artery caused compression of the artery (P = 0.0007). A mass lesion that invades the cavernous sinus and encases the internal carotid artery is very unlikely, therefore, to be a pituitary adenoma if it compresses the lumen of the internal carotid artery. PMID- 22307823 TI - 4-Hydroxyphenylglycine biosynthesis in Herpetosiphon aurantiacus: a case of gene duplication and catalytic divergence. AB - The nonproteinogenic amino acid 4-hydroxyphenylglycine (HPG) arises from the diversion of the tyrosine degradation pathway into secondary metabolism, and its biosynthesis requires a set of three enzymes. The gene cassette for HPG biosynthesis is widely spread in actinomycete bacteria, which incorporate the amino acid as a building block into various peptide antibiotics, but it has never been reported from another taxonomic group of eubacteria. A genome mining study has now revealed a putative HPG pathway in the predatory bacterium Herpetosiphon aurantiacus, which is phylogenetically distinct from Actinomycetes. Anomalies in the active center of one annotated key enzyme raised questions about the true product of this pathway, prompting an in vitro reconstitution attempt. This study confirmed the capability of H. aurantiacus for HPG production. Sequence analysis of the aberrant 4-hydroxymandelate synthase refines the existing model on the catalytic differentiation of iron(II)-dependent dioxygenases. Furthermore, we report a comprehensive analysis on the phylogeny of these enzymes, which sheds light on the evolution of paralogous gene sets and the ensuing metabolic diversity in a barely studied bacterium. PMID- 22307824 TI - Pediatric spinal glioblastoma multiforme: current treatment strategies and possible predictors of survival. AB - PURPOSE: Pediatric spinal glioblastoma multiforme (GBM) is rare. Evidence directed management relies on studies in which such cases are only a subset of a larger group. We reviewed cases of pediatric spinal GBM to assess outcomes and identify prognostic factors related to treatment. METHODS: Clinical presentations, radiologic findings, surgical variables, radio- and chemotherapeutic management, and outcomes of eight pathologically proven cases of pediatric spinal GBM were reviewed. RESULTS: Median age was 10 years. All patients presented with motor deficits. Four had sensory symptoms. Average McCormick score at presentation was II. There were three cervical, one cervicothoracic, and four thoracic tumors. Five had cysts. Patients underwent gross total resection (GTR) (n = 4), subtotal resection (STR) (n = 3), or biopsy (n = 1). Four patients improved neurologically after surgery. One patient was lost to follow-up. Seven received both chemo- and radiotherapy. Average overall survival was 15 months. Average survival after STR and GTR were 12.6 and 19.2 months, respectively. In the GTR subset, the 18-month-old patient survived 30 months, while the other two (>10 years) survived an average of 13.75 months. This difference based on age was not seen in the STR subset. Patients survived an average of 17.5 and 10.5 months, respectively, with and without tumoral cysts. Patients with cervical tumors survived an average of 12.5 months, 18.7 months with thoracic tumors, and 11.5 months with a cervicothoracic tumor. CONCLUSIONS: Tumor location, presence of a cyst, gross total resection, and younger age are possible predictors of prolonged survival. Radiotherapy and chemotherapy remain widely used. PMID- 22307825 TI - Intracranial tumors in infants: long-term functional outcome, survival, and its predictors. AB - OBJECTIVE: Intracranial tumors are rare in the first year of life. This study evaluates survival rates and functional outcomes of survivors at least 5 years after diagnosis and the predictors of this outcome. METHODS: A retrospective chart review of all infants with a primary intracranial tumor was carried out. Radiology and pathology were re-reviewed. Outcome was assessed at 5 years or more after diagnosis using Bloom's categories (Bloom 1-2 = good outcome, the rest = poor outcome) and late effects severity scoring. Age, tumor location, size, extent of tumor resection, type of adjuvant therapy given, and WHO grade of tumor histology were evaluated as predictors of outcome. RESULTS: Among 35 infants, 20 (57%) survived, with 12 (34%) having a good outcome. Deficits among the survivors included neurological dysfunction in 14 (70%), visual impairment in 9 (45%), endocrine dysfunction in 5 (25%), and auditory disability in 3 (15%). Ten of the 20 survivors were either attending regular school or were engaged in a skilled job. At presentation, older age and an infratentorial location of the tumor are predictors of poor outcome. After histopathological diagnosis, the WHO grading of tumor is the only independent predictor of survival (p = 0.002) and functional outcome (p < 0.001). CONCLUSION: About a third of the infants diagnosed with brain tumors (34%) had a good functional outcome and approximately a quarter of them (28%) were able to attend regular school or take up a skilled job. After tissue diagnosis, histological grade of tumor is the only independent predictor associated with outcome. PMID- 22307826 TI - The clinical importance of basioccipital developmental defects. PMID- 22307828 TI - Intraoperative, postoperative and reoperative problems with ileoanal pouches. AB - BACKGROUND: Proctocolectomy with ileal pouch-anal anastomosis (IPAA) has been developed and refined since its introduction in the late 1970s. Nonetheless, it is a procedure associated with significant morbidity. The aim of this review was to provide a structured approach to the challenges that surgeons and physicians encounter in the management of intraoperative, postoperative and reoperative problems associated with ileoanal pouches. METHODS: The review was based on relevant studies identified from an electronic search of MEDLINE, Embase and PubMed databases from 1975 to April 2011. There were no language or publication year restrictions. Original references in published articles were reviewed. RESULTS: Although the majority of patients experience long-term success with an ileoanal pouch, significant morbidity surrounds IPAA. Surgical intervention is often critical to achieve optimal control of the situation. CONCLUSION: A structured management plan will minimize the adverse consequences of the problems associated with pouches. PMID- 22307829 TI - High-yield assembly of soluble and stable gold nanorod pairs for high-temperature plasmonics. AB - Colloidal synthetic approaches to discrete, soluble plasmonic architectures, such as nanorod pairs, offer numerous advantages relative to lithographic techniques, including compositionally asymmetric structures, atomically smooth surfaces, and continuous fabrication. Density-driven colloidal assembly, such as by solvent evaporation, produces some intriguing structures, e.g., particle chains; however, controllability and post-processibility of the final architecture is inadequate. Also the limited quantity of product nominally comprises a broad distribution of assembly size and type. Herein, the high-yield formation of soluble, stable, and compositionally discrete gold nanorod (Au NR) architectures by inducing-then arresting-flocculation is demonstrated using bifunctional nanorods and reversible modulation of solvent quality to deplete and reassemble an electrostatic stabilization layer, thereby eliminating the need for an additional encapsulant. Analogous to dimer formation during step-growth polymerization, the initial yield of Au nanorod side-by-side pairs can be greater than 50%. The high solubility and stability of the assembly enable purification, scale-up of nanomolarity solutions, and subsequent chemical modification of the assembled product. As an example, in situ silica deposition via Stober synthesis onto the assembled pair produces highly processable nanostructures with a single pair of embedded Au NRs at their center, which exhibit thermal stability at temperatures in excess of 700 degrees C. PMID- 22307830 TI - TRESK gene recombinant adenovirus vector inhibits capsaicin-mediated substance P release from cultured rat dorsal root ganglion neurons. AB - The present study was conducted to determine whether the activation of TRESK in the dorsal root ganglion (DRG) by the TRESK gene recombinant adenovirus vector inhibits the capsaicin-evoked substance P (SP) release using a radioimmunoassay. TRESK is an outwardly rectifying K+ current channel that contributes to the resting potential and is the most important background potassium channel in DRG. Previous studies have shown that neuropathic pain (NP) is closely related to the regulation of certain potassium channels in DRG neurons, while DRG-released SP is important in the peripheral mechanism of NP. In the present study, the TRESK gene adenovirus vector significantly enhanced the TRESK mRNA and protein of the cultured rat DRG neurons. Radioimmunoassay analysis revealed that the capsaicin mediated SP release was significantly inhibited by the TRESK gene recombinant adenovirus vector in rat DRG neurons. These findings suggest that TRESK plays a role in adjusting the release of SP in DRG, which is related to NP. PMID- 22307831 TI - Presence of precore and core promoter mutants limits the probability of response to peginterferon in hepatitis B e antigen-positive chronic hepatitis B. AB - Peginterferon (PEG-IFN) treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) results in HBeAg loss in 30% of patients, but clearance of hepatitis B virus (HBV) DNA and hepatitis B surface antigen (HBsAg) from serum is less often achieved. We investigated whether the presence of precore (PC) and basal core promoter (BCP) mutants before PEG-IFN treatment affects serological and virological response. A total of 214 HBeAg-positive CHB patients treated with PEG-IFN +/- lamivudine for 52 weeks in a global randomized trial were classified at baseline as wildtype (WT) or non-WT (detectable mutants at PC/BCP) by line probe assay. Response was assessed at 6 months posttreatment and through long term follow-up (LTFU). Mutants were detected in 64% of patients, in varying frequencies across HBV genotypes A through D. Patients with WT had higher baseline HBV DNA, HBeAg, and HBsAg levels than patients with non-WT. Patients with WT were more likely to achieve HBeAg loss with HBV DNA <10,000 copies/mL (response, 34 versus 11%, P < 0.001) and HBsAg clearance (18 versus 2%, P < 0.001) at week 78 than non-WT patients. Among WT patients who achieved HBeAg clearance at week 78, 78% had undetectable HBV DNA and 61% achieved HBsAg clearance at LTFU (versus 26% and 15% in non-WT patients, P < 0.001 for both). The presence of WT virus at baseline was an independent predictor of response (odds ratio [OR] 2.90, 95% confidence interval [CI]: 1.15-7.31, P = 0.023) and HBsAg clearance (OR 5.58, 95% CI: 1.26-24.63, P = 0.013) and patients with non-A genotypes with detectable mutants had a low probability of response. CONCLUSION: The presence of only WT virus at baseline is a strong predictor of response (HBeAg loss with HBV DNA <10,000 copies/mL) to PEG-IFN for HBeAg-positive CHB. Patients with detectable PC and/or BCP mutants have a lower probability of response and are less optimal candidates for PEG-IFN therapy. PMID- 22307833 TI - Bio-protective potential of lactic acid bacteria isolated from fermented wax gourd. AB - The antifungal activities of 85 lactic acid bacteria strains isolated from fermented wax gourd against the four fungal species, Penicillium oxalicum, Aspergillus flavus, Aspergillus sydowii, and Mucor racemosus, were determined. Inhibitory activity against at least one or more fungal species was observed with 27 Weissella cibaria and 11 Weissella paramesenteroides strains. Among these strains, W. cibaria 861006 and W. paramesenteroides 860509 showed greater inhibitory activities and were therefore selected for further analysis. The results suggested that the antifungal activities were originated from the organic acids produced by W. cibaria 861006 and W. paramesenteroides 860509. The application tests indicated that the growth of P. oxalicum could be effectively inhibited by W. cibaria 861006 for 6 days on grape surfaces. However, W. paramesenteroides 860509 could only remain its inhibition effect for 48 h. The findings obtained in this study suggest the potential use of W. cibaria 861006 as a bio-protective agent against fungi for agricultural purposes or ready-to-eat fresh fruit and vegetable products. PMID- 22307832 TI - Deconstructing signal transduction pathways that regulate the actin cytoskeleton in dendritic spines. AB - Dendritic spines are the sites of most excitatory synapses in the central nervous system. Recent studies have shown that spines function independently of each other, and they are currently the smallest known processing units in the brain. Spines exist in an array of morphologies, and spine structure helps dictate synaptic function. Dendritic spines are rich in actin, and actin rearrangements are critical regulators of spine morphology and density. In this review, we discuss the importance of actin in regulating dendritic spine morphogenesis, and discuss the upstream signal transduction pathways that either foster or inhibit actin polymerization. The understanding of actin regulatory pathways is best conceptualized as a hierarchical network in which molecules function in discrete levels defined by their molecular distance to actin. To this end, we focus on several classes of molecules, including guanine nucleotide exchange factors, small GTPases, small GTPase effectors, and actin binding proteins. We discuss how individual proteins in these molecular classes impact spine morphogenesis, and reveal the biochemical interactions in these networks that are responsible for shaping actin polymerization. Finally, we discuss the importance of these actin regulatory pathways in neuropsychiatric disorders. PMID- 22307835 TI - A theoretical investigation into the 1,3-dipolar cycloaddition of azidotrimethylsilane onto nanographene. AB - The mechanism of the 1,3-dipolar cycloaddition reaction of azidotrimethylsilane (ATS) onto nanographene (NG) is thoroughly investigated at the B3LYP/6-31G(d,p) level. Calculations reveal that the reaction occurs through a two-step reaction mechanism. The first step is the chemical adsorption and the second one is the decomposition of the thereby formed nitride upon thermal activation, giving rise to an N-bridged product ultimately. The latter is the rate-determining step. Two possible pathways are compared to show that the [3+2] channel is favored over the [3+4] channel. The former is a symmetric synchronous process, whereas the latter follows an asymmetric concerted way, which can be rationalized by means of the frontier molecular orbital (FMO) theory. The reactivity of NG is discussed in detail, revealing that it is the electron density at the functionalization site which dominates the reactivity rather than the energetic effect. As a result, the edge area is calculated to be much more reactive than the centre. PMID- 22307834 TI - Antimicrobial resistance in Salmonella spp. recovered from patients admitted to six different hospitals in Tehran, Iran from 2007 to 2008. AB - The objective of this study was to assess the genotypic diversity associated with antimicrobial susceptibility of Salmonella serovars isolated from patients arriving with diarrhoea to six hospitals of Tehran, Iran. During 2007-2008, a cross-sectional convenience study was performed. Stool samples were screened for the presence of Salmonella, serotyped, tested for antimicrobial susceptibility using disk diffusion and examined for the presence of relevant resistance genes and integrons by PCR. A total of 1,120 patients were screened for the presence of Salmonella. Out of 71 Salmonella isolates recovered, the following serovars were identified: 17 Typhi, 14 Paratyphi C, 13 Enteritidis, 11 Paratyphi B, 10 Paratyphi A and six Infantis. Most resistance was observed towards sulfamethoxazole (30%), tetracyclines (25%), nalidixic acid (22%), spectinomycin (17%), trimethoprim (15%), ampicillin (14%) and kanamycin (14%). The tetracycline resistance genes tet(A), tet(B), and tet(G) were found in 28%, 14% and 6% of the tetracycline resistant isolates, respectively. The genes aadA, aadB, strA, strB and aphA1-Iab were present in 83%, 55%, 34%, 1% and 17% of the aminoglycoside resistant isolates, respectively. Additionally, bla (PSE) and bla (TEM) beta lactamase genes were detected in 63% and 18% of the ampicillin-resistant isolates. The 23 sulphonamide resistant isolates harboured sul1 and intI1 genes, typical to class 1 integrons. Nine of these isolates also yielded amplicons for intI2 (class 2 integrons). The presence of multi-drug resistant Salmonella may compromise the successful treatment of enteric infection diseases. The enforcement of strict prescription practices will help to minimise the emergence of resistance. PMID- 22307836 TI - Carcinosarcoma de novo of the parotid gland: case report. AB - BACKGROUND: Salivary gland carcinosarcoma is a rare and aggressive malignant mixed tumor in which carcinomatous and sarcomatous elements coexist and metastasize together. The tumor may occur in the background of a preexisting pleomorphic adenoma or may arise de novo. We report a case of a woman presenting with a carcinosarcoma de novo of the parotid gland. METHODS AND RESULTS: Our patient underwent surgical resection and adjuvant radiotherapy and demonstrates no evidence of recurrence at 14 months posttreatment. CONCLUSIONS: Review of the literature supports combined modality, surgery with postoperative radiation, as the standard of care for this malignancy, although the long-term prognosis for these patients is unclear. PMID- 22307837 TI - Total synthesis of laulimalide: synthesis of the northern and southern fragments. AB - The first stage in the development of a synthetic route for the total synthesis of laulimalide (1) is described. Our retrosynthetic analysis envisioned a novel macrocyclization route to the natural product by using a Ru-catalyzed alkene alkyne coupling. This would be preceded by an esterification of the C19 hydroxyl group, joining together two equally sized synthons, the northern fragment 7 and the southern fragment 8. Our first generation approach to the northern fragment entailed a key sequential Ru/Pd coupling sequence to assemble the dihydropyran. The key reactions proceeded smoothly, but the inability to achieve a key olefin migration led to the development of an alternative route based on an asymmetric dinuclear Zn-catalyzed aldol reaction of a hydroxyl acylpyrrole. This key reaction led to the desired diol adduct 66 with excellent syn/anti selectivity (10:1), and allowed for the successful completion of the northern fragment 7. The key step for the synthesis of the southern fragment was a chemoselective Rh catalyzed cycloisomerization reaction to form the dihydropyran ring from a diyne precursor. This reaction proved to be selective for the formation of a six membered ring, over a seven. The use of an electron-deficient bidentate phosphine allowed for the reaction to proceed with a reduced catalyst loading. PMID- 22307838 TI - The dark side of mast cell-targeted therapy in prostate cancer. AB - Tumor development requires accomplices among white blood cells. Other than macrophages, mast cells have been observed to support the outgrowth of certain neoplasias because of their proangiogenic properties. In some tumor settings, however, mast cells may have a protective role, exerted by their proinflammatory mediators. In prostate cancer, no conclusive data on mast cell function were available. Here, we discuss recent work on the role of mast cells in mouse and human prostate cancer, showing that mast cells can behave alternatively as dangerous promoters, innocent bystanders, or essential guardians of tumors, according to the stage and origin of transformed cells. In particular, mast cells are essential for the outgrowth of early-stage tumors due to their matrix metalloproteinase-9 production, become dispensable in advanced-stage, post epithelial-to-mesenchymal transition, and are protective against neuroendocrine prostate tumor variants. The common expression of c-Kit by mast cells and neuroendocrine clones suggests a possible competition for the ligand Stem cell factor and offers the chance of curing early-stage disease while preventing neuroendocrine tumors using c-Kit-targeted therapy. This review discusses the implications of these findings on the advocated mast cell-targeted cancer therapy and considers future directions in the study of mast cells and their interactions with other c-Kit-expressing cells. PMID- 22307840 TI - Mammary tumor regression elicited by Wnt signaling inhibitor requires IGFBP5. AB - Wnt ligand-driven tumor growth is inhibited by the soluble Wnt inhibitor Fzd8CRD, but the mechanism through which this effect is mediated is unknown. In the MMTV Wnt1 mouse model, regression of mammary tumors by Fzd8CRD treatment coincides with an acute and strong induction of insulin-like growth factor (IGF)-binding protein IGFBP5, an antagonist of IGF signaling that mediates involution of mammary gland in females after offspring are weaned. In this study, we show that repression of this IGF inhibitory pathway is crucial for Wnt-driven growth of mammary tumors. We found that IGFBP5 regulation was mediated by the beta-catenin dependent Wnt pathway. Wnt, in addition to IGF ligands, facilitated tumor growth by paracrine communication among tumor cells. In addition, Fzd8CRD caused precocious induction of IGFBP5 in normal mammary glands undergoing involution, implying an acceleration of the involution process by inhibition of Wnt signaling. The molecular and phenotypic parallel between tumor regression and mammary gland involution suggests that Wnt-driven mammary tumors use the same growth mechanism as proliferating normal mammary glands. PMID- 22307839 TI - Reprogramming tumor-associated dendritic cells in vivo using miRNA mimetics triggers protective immunity against ovarian cancer. AB - Modulating the activity of miRNAs provides opportunities for novel cancer interventions. However, low bioavailability and poor cellular uptake are major challenges for delivering miRNA mimetics specifically to tumor cells. Here, we took advantage of the spontaneous enhanced endocytic activity of ovarian cancer associated dendritic cells (DC) to selectively supplement the immunostimulatory miRNA miR-155. In vivo processing of nanoparticles carrying oligonucleotide duplexes mimicking the bulged structure of endogenous pre-miRNA (but not siRNA like oligonucleotides) dramatically augmented miR-155 activity without saturating the RNA-induced silencing complex. Endogenous processing of synthetic miR-155 favored Ago2 and, to a lesser extent, Ago4 loading, resulting in genome-wide transcriptional changes that included silencing of multiple immunosuppressive mediators. Correspondingly, tumor-infiltrating DCs were transformed from immunosuppressive to highly immunostimulatory cells capable of triggering potent antitumor responses that abrogated the progression of established ovarian cancers. Our results show both the feasibility and therapeutic potential of supplementing/replenishing miRNAs in vivo using nonviral approaches to boost protective immunity against lethal tumors. Thus, we provide a platform, an optimized design, and a mechanistic rationale for the clinical testing of nonviral miRNA mimetics. PMID- 22307841 TI - Bacterial community structure in the rhizosphere of three cactus species from semi-arid highlands in central Mexico. AB - The nature reserve of Tehuacan-Cuicatlan in central Mexico is known for its diversity and endemism mainly in cactus plants. Although the xerophytic flora is reasonably documented, the bacterial communities associated with these species have been largely neglected. We assessed the diversity and composition of bacterial communities in bulk (non-rhizospheric) soil and the rhizosphere of three cactus plant species: Mammillaria carnea, Opuntia pilifera and Stenocereus stellatus, approached using cultivation and molecular techniques, considering the possible effect of dry and rainy seasons. Cultivation-dependent methods were focused on putative N(2)-fixers and heterotrophic aerobic bacteria, in the two media tested the values obtained for dry season samples grouped together regardless of the sample type (rhizospheric or non-rhizospheric), these groups also included the non-rhizospheric sample for rainy season, on each medium. These CFU values were smaller and significantly different from those obtained on rhizospheric samples from rainy season. Genera composition among isolates of the rhizospheric samples was very similar for each season, the most abundant taxa being alpha-Proteobacteria, Actinobacteria and Firmicutes. Interestingly, the genus Ochrobactrum was highly represented among rhizospheric samples, when cultured in N-free medium. The structure of the bacterial communities was approached with molecular techniques targeting partial 16S rRNA sequences such as denaturing gradient gel electrophoresis and serial analysis of ribosomal sequence tags. Under these approaches, the most represented bacterial phyla were Actinobacteria, Proteobacteria and Acidobacteria. The first two were also highly represented when using isolation techniques. PMID- 22307842 TI - Baseline NT-proBNP and biomarkers of inflammation and necrosis in patients with ST-segment elevation myocardial infarction: insights from the APEX-AMI trial. AB - Coronary plaque rupture is associated with a systemic inflammatory response. The relationship between baseline N-terminal pro B-type natriuretic peptide (NT proBNP), a prognostic marker in patients with acute coronary syndromes, and systemic inflammatory mediators in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) is not well described. Of 5,745 STEMI patients treated with primary PCI in the APEX-AMI trial, we evaluated the relationship between baseline NT-proBNP levels and baseline levels of inflammatory markers and markers of myonecrosis in a subset of 772 who were enrolled in a biomarker substudy. Spearman correlations (r (s)) were calculated between baseline NT-proBNP levels and a panel of ten systemic inflammatory biomarkers. Interleukin (IL)-6, a pro-inflammatory cytokine, was significantly positively correlated with NT-proBNP (r (s) = 0.317, P < 0.001). In a sensitivity analysis excluding all heart failure patients, the correlation between baseline IL-6 and NT-proBNP remained significant (n = 651, r (s) = 0.296, P < 0.001). A positive association was also observed with high sensitivity C-reactive protein (r (s) = 0.377, P < 0.001) and there was a weak negative correlation with the anti-inflammatory cytokine IL-10 (r (s) = -0.109, P = 0.003). No other significant correlations were observed among the other testes inflammatory cytokines and chemokines. In STEMI patients undergoing primary PCI, the pro-inflammatory cytokine IL-6 was modestly correlated with baseline NT proBNP levels. This relationship remained significant in patients without heart failure. This finding is consistent with pre-clinical and clinical research suggesting that systemic inflammation may influence NT-proBNP expression independently of myocardial stretch. PMID- 22307843 TI - Blunted heart rate circadian rhythms in small for gestational age infants during the early neonatal period. AB - Infants born with intrauterine growth restriction are at increased risk for adverse cardiovascular outcomes in neonatal and later life. Although circadian rhythm is a prognostic marker of cardiovascular health, the concern over the circadian rhythm of these infants is rarely observed. To determine the influence of intrauterine growth retardation on the pattern of circadian rhythm, heart rate (HR) circadian rhythmicity was analyzed in 39 small for gestational age (SGA; birth weight and height below <-2.0 standard deviation score [SDS]) and 117 appropriate for gestational age (AGA; >-1.5 to <1.5 SDS) infants within 72 hours of birth using spectral analysis and cosinor analysis. Amplitude, midline estimating statistic of rhythm, and acrophase calculated from circadian rhythm were analyzed with clinical variables. A significant HR circadian rhythm was observed in 23.1% of the SGA and 24.8% of the AGA group without significant differences; however, SGA infants exhibited remarkable smaller amplitudes compared with AGA in all gestational age (GA) groups (p < 0.001). Amplitudes in AGA infants were positively correlated with the GA or body composition relevant variables (p < 0.001, respectively), but not SGA infants. The blunted HR circadian rhythmicity in SGA infants showed in this study might indicate the vulnerability to pathophysiological condition and could potentially refer to cardiovascular disease in later life. PMID- 22307844 TI - Acid-base parameters for predicting magnetic resonance imaging measures of neurologic outcome after perinatal hypoxia-ischemia: is the strong ion gap superior to base excess and lactate? AB - We conducted this study to compare the strong ion gap (SIG) with base excess (BE) and lactate for predicting neurologic outcome measured by magnetic resonance imaging (MRI) in newborns with hypoxic-ischemic encephalopathy (HIE). In a retrospective cohort of 39 newborns with HIE treated with whole-body surface cooling (n = 17) and no cooling (n = 22), we measured blood SIG, BE, and lactate at 4, 24, and 48 hours after birth, and determined cerebral injury severity by T1 , T2-, and diffusion-weighted MRI scores at age 5 days. Lower SIG levels correlated with better neurologic outcome. The highest correlation coefficient (0.63) was in the "no cooling" subcohort between diffusion-weighted scores and SIG levels at 24 hours; the latter also had the highest area under the receiver operating characteristic curve (AUC), 0.90, with positive and negative predictive values of 84 and 90%. SIG outperformed lactate in the "no cooling" subcohort, and vice-versa in the "cooling" subcohort. All BE AUCs were <0.6. Overall, the SIG is similar to lactate as a prognostic parameter. BE levels at 4, 24, and 48 hours after birth do not predict neurologic outcome. While not displacing lactate the SIG is an additional prognostic parameter for newborns in the first 2 days after hypoxia-ischemia. PMID- 22307845 TI - Low HCMV DNA copies can establish infection and result in significant symptoms in extremely preterm infants: a prospective study. AB - Breast milk (BM) is the main source of human cytomegalovirus (HCMV) infection. We examined whether the number of HCMV DNA copies in BM is related to HCMV infection in very low birth weight (VLBW) infants. We identified 11 pairs of VLBW infants and mothers. BM samples were collected every week until 10 weeks postpartum. Urine samples were collected from the infants within 1 week, at 6 to 8 weeks, at discharge, and whenever HCMV infection was suspected. HCMV DNA in BM was positive in 7 of 11 mothers and reached a peak at 4 to 5 weeks postpartum. Of the 11, 5 infants were determined to be infected from positive HCMV DNA in the urine, despite the fact that BM was used after being frozen. Of the five, four infected infants exhibited symptoms between 35 and 60 days of age. Symptomatic infants had longer stays and slower weight gain. The HCMV infection rate is high in very preterm infants. A new strategy to prevent HCMV infection other than freezing should therefore be established. PMID- 22307846 TI - Rectocele--does the size matter? AB - OBJECTIVES: Large rectoceles (>2 cm) are believed to be associated with difficulty in evacuation, constipation, rectal pain, and rectal bleeding. The aim of our study was to determine whether rectocele size is related to patient's symptoms or defecatory parameters. METHODS: We conducted a retrospective study on data collected on patients referred to our clinic for the evaluation of evacuation disorders. All patients were questioned for constipation, fecal incontinence, and irritable bowel syndrome and were assessed with dynamic perineal ultrasonography and conventional anorectal manometry. RESULTS: Four hundred eighty-seven women were included in our study. Rectocele was diagnosed in 106 (22%) women, and rectocele diameter >2 cm in 93 (87%) women. Rectocele size was not significantly related to demographic data, parity, or patient's symptoms. The severity of the symptoms was not correlated to the size or to the position of the rectocele. The diagnosis of irritable bowel syndrome was neither related to the size of the rectocele. Rectocele location, occurrence of enterocele, and intussusception were not related to the size of the rectocele. Full evacuation of rectoceles was more common in small rectoceles (79% vs. 24%, p = 0.0001), and no evacuation was more common in large rectoceles (37% vs. 0, p = 0.01). Rectal hyposensitivity and anismus were not related to the size of the rectocele. CONCLUSION: In conclusion, only the evacuation of rectoceles was correlated to the size of the rectoceles, but had no clinical significance. Other clinical, anatomical factors were also not associated to the size of the rectoceles. Rectoceles' size alone may not be an indication for surgery. PMID- 22307847 TI - Answer to the Letter to the Editor of G. Supp concerning manuscript "Centralization in patients with sciatica: are pain responses to repeated movement and positioning associated with outcome or types of disc lesions?"by Hanne B. Albert et al. Eur Spine J, 2011 Sept 23 [Epub ahead of print]. PMID- 22307848 TI - Diarrhea predicts a positive response to sorafenib in patients with advanced hepatocellular carcinoma. PMID- 22307849 TI - microRNA-155 silencing inhibits proliferation and migration and induces apoptosis by upregulating BACH1 in renal cancer cells. AB - The purpose of this study was to explore the functional role and mechanism of miR 155 in the development of renal cell carcinoma (RCC). miR-155 expression was quantified in renal cancers, matched adjacent non-tumor tissues and renal cell lines using quantitative real-time PCR (RT-PCR). Cell proliferation, apoptosis and migratory activity were measured following suppression of miR-155 expression by antisense oligonucleotides. miR-155 targets were scanned using target prediction programs. Following the inhibition of miR-155, target gene expression was detected by western blotting. The expression of miR-155 was upregulated in clear cell RCC (ccRCC) tissue and renal cancer cell lines. The suppression of miR 155 inhibited cell proliferation and migratory activity and induced apoptosis in renal cancer cells. The suppressor gene suppressor of cytokine signaling (SOCS-1) and BACH1 were predicted as potential target genes by bioinformatics analysis. The suppression of miR-155 inhibited BACH1 protein expression. miR-155 may function as an oncogene by targeting BACH1. Thus, the inhibition of miR-155 may be an effective way to treat RCC. PMID- 22307851 TI - Mutations in the Arabidopsis homolog of LST8/GbetaL, a partner of the target of Rapamycin kinase, impair plant growth, flowering, and metabolic adaptation to long days. AB - The conserved Target of Rapamycin (TOR) kinase forms high molecular mass complexes and is a major regulator of cellular adaptations to environmental cues. The Lethal with Sec Thirteen 8/G protein beta subunit-like (LST8/GbetaL) protein is a member of the TOR complexes, and two putative LST8 genes are present in Arabidopsis thaliana, of which only one (LST8-1) is significantly expressed. The Arabidopsis LST8-1 protein is able to complement yeast lst8 mutations and interacts with the TOR kinase. Mutations in the LST8-1 gene resulted in reduced vegetative growth and apical dominance with abnormal development of flowers. Mutant plants were also highly sensitive to long days and accumulated, like TOR RNA interference lines, higher amounts of starch and amino acids, including proline and glutamine, while showing reduced concentrations of inositol and raffinose. Accordingly, transcriptomic and enzymatic analyses revealed a higher expression of genes involved in nitrate assimilation when lst8-1 mutants were shifted to long days. The transcriptome of lst8-1 mutants in long days was found to share similarities with that of a myo-inositol 1 phosphate synthase mutant that is also sensitive to the extension of the light period. It thus appears that the LST8-1 protein has an important role in regulating amino acid accumulation and the synthesis of myo-inositol and raffinose during plant adaptation to long days. PMID- 22307852 TI - Evidence for a role of VIPP1 in the structural organization of the photosynthetic apparatus in Chlamydomonas. AB - The vesicle-inducing protein in plastids (VIPP1) was suggested to play a role in thylakoid membrane formation via membrane vesicles. As this functional assignment is under debate, we investigated the function of VIPP1 in Chlamydomonas reinhardtii. Using immunofluorescence, we localized VIPP1 to distinct spots within the chloroplast. In VIPP1-RNA interference/artificial microRNA cells, we consistently observed aberrant, prolamellar body-like structures at the origin of multiple thylakoid membrane layers, which appear to coincide with the immunofluorescent VIPP1 spots and suggest a defect in thylakoid membrane biogenesis. Accordingly, using quantitative shotgun proteomics, we found that unstressed vipp1 mutant cells accumulate 14 to 20% less photosystems, cytochrome b(6)f complex, and ATP synthase but 30% more light-harvesting complex II than control cells, while complex assembly, thylakoid membrane ultrastructure, and bulk lipid composition appeared unaltered. Photosystems in vipp1 mutants are sensitive to high light, which coincides with a lowered midpoint potential of the Q(A)/Q(A)(-) redox couple and increased thermosensitivity of photosystem II (PSII), suggesting structural defects in PSII. Moreover, swollen thylakoids, despite reduced membrane energization, in vipp1 mutants grown on ammonium suggest defects in the supermolecular organization of thylakoid membrane complexes. Overall, our data suggest a role of VIPP1 in the biogenesis/assembly of thylakoid membrane core complexes, most likely by supplying structural lipids. PMID- 22307853 TI - Lectin-mediated resistance impairs plant virus infection at the cellular level. AB - Plants possess a multilayered defense response, known as plant innate immunity, to infection by a wide variety of pathogens. Lectins, sugar binding proteins, play essential roles in the innate immunity of animal cells, but the role of lectins in plant defense is not clear. This study analyzed the resistance of certain Arabidopsis thaliana ecotypes to a potexvirus, plantago asiatica mosaic virus (PlAMV). Map-based positional cloning revealed that the lectin gene JACALIN TYPE LECTIN REQUIRED FOR POTEXVIRUS RESISTANCE1 (JAX1) is responsible for the resistance. JAX1-mediated resistance did not show the properties of conventional resistance (R) protein-mediated resistance and was independent of plant defense hormone signaling. Heterologous expression of JAX1 in Nicotiana benthamiana showed that JAX1 interferes with infection by other tested potexviruses but not with plant viruses from different genera, indicating the broad but specific resistance to potexviruses conferred by JAX1. In contrast with the lectin gene RESTRICTED TEV MOVEMENT1, which inhibits the systemic movement of potyviruses, which are distantly related to potexviruses, JAX1 impairs the accumulation of PlAMV RNA at the cellular level. The existence of lectin genes that show a variety of levels of virus resistance, their targets, and their properties, which are distinct from those of known R genes, suggests the generality of lectin mediated resistance in plant innate immunity. PMID- 22307856 TI - Total synthesis of laulimalide: assembly of the fragments and completion of the synthesis of the natural product and a potent analogue. AB - Herein, we present a full account of our efforts to couple the northern and the southern building blocks, the synthesis of which were described in the preceding paper, along with the modifications required to ultimately lead to a successful synthesis of laulimalide. Key highlights include an exceptionally efficient and atom-economical intramolecular ruthenium-catalyzed alkene-alkyne coupling to build the macrocycle, followed by a highly stereoselective 1,3-allylic isomerization promoted by a rhenium complex. Interestingly, the designed synthetic route also allowed us to prepare an analogue of the natural product that possesses significant cytotoxic activity. We also report a second generation route that provides a more concise synthesis of the natural product. PMID- 22307857 TI - C/EBP-alpha ameliorates CCl(4)-induced liver fibrosis in mice through promoting apoptosis of hepatic stellate cells with little apoptotic effect on hepatocytes in vitro and in vivo. AB - CCAAT enhancer binding protein-alpha (C/EBP-alpha) is a transcript factor that regulates adipocyte differentiation and induces apoptosis in hepatic stellate cells (HSCs) in vivo and in vitro. However, the effect of C/EBP-alpha on hepatocytes in vivo remains unknown. This study investigated whether C/EBP-alpha exerts different apoptotic effects on hepatocytes and HSCs in vitro and in vivo. An adenovirus vector-expressing C/EBP-alpha gene was constructed, and a rat hepatic stellate cell lines (HSC-T6) and hepatocytes were transfected. A CCl(4) induced liver fibrosis model in mice was also utilized. C/EBP-alpha induced apoptosis in hepatocytes and HSCs, but a significant difference between these cell types was observed in vitro. The mitochondrial pathway was involved in the apoptotic process and was predominant in HSC-T6 apoptosis. In the CCl(4)-induced mice liver fibrosis model, the administration of Ad-C/EBP-alpha decreased extracellular matrix deposition, including collagen and hydroxyproline content, and gamma-GT levels, a marker of liver damage, were reduced significantly. Immunohistochemistry and TUNEL assay results showed an increase of apoptosis in HSCs, but hepatocytes were less affected. C/EBP-alpha induced differential apoptotic effects in hepatocytes and HSCs in vitro and in vivo. This differential effect could be a potential target for the treatment of hepatic fibrosis with little hepatic toxicity. PMID- 22307858 TI - Cognitive deficits in Machado-Joseph disease correlate with hypoperfusion of visual system areas. AB - Cognitive and olfactory impairments have previously been demonstrated in patients with spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD)-SCA3/MJD. We investigated changes in regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT) imaging in a cohort of Brazilian patients with SCA3/MJD. The aim of the present study was to evaluate the correlation among rCBF, cognitive deficits, and olfactory dysfunction in SCA3/MJD. Twenty-nine genetically confirmed SCA3/MJD patients and 25 control subjects were enrolled in the study. The severity of cerebellar symptoms was measured using the International Cooperative Ataxia Rating Scale and the Scale for the Assessment and Rating of Ataxia. Psychiatric symptoms were evaluated by the Hamilton Anxiety Scale and Beck Depression Inventory. The neuropsychological assessment consisted of Spatial Span, Symbol Search, Picture Completion, the Stroop Color Word Test, Trail Making Test (TMT), and Phonemic Verbal Fluency. Subjects were also submitted to odor identification evaluation using the 16-item Sniffin' Sticks. SPECT was performed using ethyl cysteine dimer labeled with technetium-99m. SCA3/MJD patients showed reduced brain perfusion in the cerebellum, temporal, limbic, and occipital lobes compared to control subjects (pFDR <0.001). A significant positive correlation was found between the Picture Completion test and perfusion of the left parahippocampal gyrus and basal ganglia in the patient group as well as a negative correlation between the TMT part A and bilateral thalamus perfusion. The visuospatial system is affected in patients with SCA3/MJD and may be responsible for the cognitive deficits seen in this disease. PMID- 22307860 TI - Evaluation of plant-growth-promoting rhizobacteria, acibenzolar-S-methyl and hymexazol for integrated control of Fusarium crown and root rot on tomato. AB - BACKGROUND: Plant growth-promoting rhizobacteria (PGPR) can be potential agents for biological control of plant pathogens, while their combined use with conventional pesticides may increase their efficacy and broaden the disease control spectrum. The effect of four different Bacillus sp. PGPR strains (B. subtilis GB03 and FZB24, B. amyloliquefaciens IN937a and B. pumilus SE34) applied individually and in mixtures, as well as in combined use with acibezolar-S-methyl (ASM) and hymexazol, on plant growth promotion and on the control of Fusarium crown and root rot (FCRR) of tomato was evaluated. RESULTS: All PGPR strains promoted the tested plant growth characteristics significantly. A higher promoting effect was provided by SE34. Experiments on population dynamics of PGPR strains revealed that, after 28 days of incubation, populations of strain SE34 remained stable, while the remaining bacterial strains showed a slight decline in their population densities. The GB03 and FZB24 strains provided a higher disease suppression when applied individually. However, application of IN937a in a mixture with GB03 provided a higher control efficacy of Fusarium oxysporum f. sp. radicis-lycopersici (Forl). Treatment of tomato plants with ASM resulted in a small reduction in disease index, while application of hymexazol provided significantly higher control efficacy. Combined applications of the four PGPR strains with either ASM or hymexazol were significantly more effective. CONCLUSION: The results of the study indicate that, when bacilli PGPR strains were combined with pesticides, there was an increased suppression of Forl on tomato plants, and thus they may prove to be important components in FCRR integrated management. PMID- 22307861 TI - Effects of lower limb prosthesis on activity, participation, and quality of life: a systematic review. AB - BACKGROUND: Effects presented on the use of assistive devices such as prosthesis are often based on laboratory findings (i.e. efficacy). OBJECTIVES: To summarise and evaluate findings from studies on effectiveness of lower limb prostheses for adults in real life contexts, primarily in terms of activity, participation, and quality of life (QoL) and secondarily in terms of user satisfaction, use/non-use, and/or cost-effectiveness. STUDY DESIGN: Systematic review. METHODS: We included controlled studies and non-controlled follow-up studies including both baseline and follow-up data. Using 14 different databases supplemented with manual searches, we searched for studies published from 1998 until June 2009. RESULTS: Out of an initial 818 identified publications, eight met the inclusion criteria. Four studies reported on the effectiveness of a microprocessor-controlled knee (MP-knee) compared to a non-microprocessor-controlled knee (NMP-knee). Results were inconsistent except for quality of life and use/non-use, where the authors reported an improvement with the MP-knee compared to the NMP-knee. The remaining four studies included a diversity of prosthetic intervention measures and types of endpoints. CONCLUSIONS: Overall, there was an inconsistency in results and study quality. This review highlights the need for high-quality research studies that reflect the effectiveness of different prosthesis interventions in terms of users' daily living and QoL. CLINICAL RELEVANCE: Clinical guidelines are important to every practitioner. Information on expected effectiveness from assistive devices should be well founded and contain both facts about the device quality and its contribution to users' daily lives. Thus, studies based on users' experiences from prosthetic use in everyday life activities are of great importance. PMID- 22307862 TI - Prosthetic limb sockets from plant-based composite materials. AB - BACKGROUND: There is a considerable demand for lower limb prostheses globally due to vascular disease, war, conflict, land mines and natural disasters. Conventional composite materials used for prosthetic limb sockets include acrylic resins, glass and carbon fibres, which produce harmful gasses and dust in their manufacture. OBJECTIVES: To investigate the feasibility of using a renewable plant oil-based polycarbonate-polyurethane copolymer resin and plant fibre composite, instead of conventional materials, to improve safety and accessibility of prosthetic limb manufacture. STUDY DESIGN: Experimental, bench research. METHODS: Test pieces of the resin with a range of plant fibres (10.0% by volume) were prepared and tensile strengths were tested. Test sockets of both conventional composite materials and plant resin with plant fibres were constructed and tested to destruction. RESULTS: Combinations of plant resin and either banana or ramie fibres gave high tensile strengths. The conventional composite material socket and plant resin with ramie composite socket failed at a similar loading, exceeding the ISO 10328 standard. Both wall thickness and fibre matrix adhesion played a significant role in socket strength. CONCLUSIONS: From this limited study we conclude that the plant resin and ramie fibre composite socket has the potential to replace the standard layup. Further mechanical and biocompatibility testing as well as a full economic analysis is required. CLINICAL RELEVANCE: Using readily sourced and renewable natural fibres and a low volatile bio-resin has potential to reduce harm to those involved in the manufacture of artificial limb sockets, without compromising socket strength and benefitting clinicians working in poorer countries where safety equipment is scarce. Such composite materials will reduce environmental impact. PMID- 22307863 TI - Proposal of landmarks for clamping neurovascular elements during endoscopic surgery of the supraglottic region. AB - BACKGROUND: Bleeding within the supraglottic region can be a lethal complication after CO(2) laser microsurgery. Our aim was to propose endoluminal anatomical landmarks to locate the superior laryngeal vessels resulting in a safer microsurgery. METHODS: Endoluminal dissections were made in 22 larynges without laryngeal disease. RESULTS: The neurovascular structures were in the superior third of a triangle defined by the vocal process, the anterior commissure, and the epiglottic attachment of the aryepiglottic fold. They overlapped in 4 different ways: pattern I (70.4%): superior laryngeal vein (SLV), superior laryngeal artery (SLA), and internal laryngeal nerve (ILN); pattern II (13.6%): SLA, SLV, ILN; pattern III (4.6%): SLV, ILN, and SLA; pattern IV (4.6%): SLA, ILN, and SLV. CONCLUSION: Microsurgery in the supraglottic region may be safer if surgeons are aware of the superior third of the above-defined triangle, "danger area", where the vascular elements of this region are located. PMID- 22307865 TI - Role of leptin as antioxidant in obstructive sleep apnea: an in vitro study using electron paramagnetic resonance method. AB - INTRODUCTION: As in obstructive sleep apnea (OSA), the chronic cycles of hypoxia and reoxygenation are thought to be conducive of oxidative stress (OS) with generation of reactive oxygen species, identifying effective mechanisms of protection against oxidant-mediated tissue damage becomes of outmost importance. Leptin's role had been recently extended into that of participant to OS; while its exact role in this process is yet to be defined, elevated leptin levels correlate significantly with several indices of OSA disease severity such as nocturnal hypoxemia, possibly acting as a counteractive mechanism against the chronic intermittent hypoxia-related OS and serving as a marker of future risk of atherosclerotic disease. We therefore investigated leptin's antioxidant mechanism on superoxide (O (2) (-*) ) anions using spectrophotometry and electron paramagnetic resonance (EPR). METHODS: The O (2) (-*) was generated by oxidation of xanthine (XAN) by xanthine oxidase (XO) in the presence of spin trap 5 diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide with various concentrations of leptin (0.001, 0.01, 0.1, and 1 mg/ml) and without leptin. Signal intensity between 3,440 and 3,540 G was expressed as standard means +/- SD. The activity of leptin on XO was determined by monitoring the conversion of XAN to uric acid at 293 nm using a Beckman DU 800 UV-visible spectrophotometer. RESULTS: Leptin added to aqueous solutions at 0.1 and 1 mg/ml concentrations was associated with a statistically significant decrease in the EPR signal due to leptin's direct scavenging activity towards the O (2) (-*) . CONCLUSION: Leptin is an antioxidant agent of possible use as a marker of OS and future risk of atherosclerotic disease in OSA. PMID- 22307866 TI - Comparison of right ventricular longitudinal strain imaging, tricuspid annular plane systolic excursion, and cardiac biomarkers for early diagnosis of cardiac involvement and risk stratification in primary systematic (AL) amyloidosis: a 5 year cohort study. AB - AIMS: To determine the role of assessing right ventricular (RV) function, using standard echocardiography and Doppler myocardial imaging (DMI), in the early diagnosis of cardiac amyloidosis and in the prediction of mortality. METHODS AND RESULTS: Patients with primary systemic (AL) amyloidosis seen at our institution from 1 February 2004 through 31 October 2005 (N=249) were categorized by left ventricular thickness and E' velocity and compared with 38 age- and sex-matched controls. Standard echocardiographic and DMI examination were used to measure echocardiographic parameters of RV function: systolic tissue velocity, strain rate, and strain were determined for basal and middle RV free wall segments. Patients were followed up for the endpoint of mortality. RV tricuspid annular plane systolic excursion (TAPSE) and all DMI measurements were lower in patients with AL amyloidosis and normal echocardiography results (AL-normal-echo group) than controls. A bivariate model including strain of the basal segment of the RV free wall and TAPSE was the best for distinguishing AL-normal-echo patients from controls. Male sex [hazard ratio (HR), 2.2; P=0.005], brain natriuretic peptide levels (HR 1.4; P=0.003), troponin T levels (HR 1.6; P=0.01), pleural effusion (HR 3.6; P<0.001), E/A ratio (HR 1.3; P=0.006), RV systolic pressure (HR 1.02; P=0.01), and RV strain rate of the middle segment (HR 1.3; P=0.02) were independent predictors of death. CONCLUSION: DMI measures of the RV can identify early impairment of cardiac function or stratify risk of death in patients with AL amyloidosis. Further studies with longer follow-up are warranted to confirm these results. PMID- 22307864 TI - Cancer risks associated with external radiation from diagnostic imaging procedures. AB - The 600% increase in medical radiation exposure to the US population since 1980 has provided immense benefit, but increased potential future cancer risks to patients. Most of the increase is from diagnostic radiologic procedures. The objectives of this review are to summarize epidemiologic data on cancer risks associated with diagnostic procedures, describe how exposures from recent diagnostic procedures relate to radiation levels linked with cancer occurrence, and propose a framework of strategies to reduce radiation from diagnostic imaging in patients. We briefly review radiation dose definitions, mechanisms of radiation carcinogenesis, key epidemiologic studies of medical and other radiation sources and cancer risks, and dose trends from diagnostic procedures. We describe cancer risks from experimental studies, future projected risks from current imaging procedures, and the potential for higher risks in genetically susceptible populations. To reduce future projected cancers from diagnostic procedures, we advocate the widespread use of evidence-based appropriateness criteria for decisions about imaging procedures; oversight of equipment to deliver reliably the minimum radiation required to attain clinical objectives; development of electronic lifetime records of imaging procedures for patients and their physicians; and commitment by medical training programs, professional societies, and radiation protection organizations to educate all stakeholders in reducing radiation from diagnostic procedures. PMID- 22307867 TI - Paramandibular abscess following trans-oesophageal echocardiography. PMID- 22307868 TI - Doppler haemodynamics and effective orifice areas of Edwards SAPIEN and CoreValve transcatheter aortic valves. AB - AIMS: Transcatheter aortic valve implantation (TAVI) is a new therapy for severe aortic stenosis in high-risk patients. So far, no reference values for the echocardiographic assessment of this new class of heart valves have been established. The aim of our study was to determine Doppler haemodynamics and the effective orifice area (EOA). METHODS AND RESULTS: We retrospectively analysed the earliest transthoracic echocardiographic examinations of 146 stable patients after successful TAVI (median 8+/-20 days). Doppler examinations were analysed for peak instantaneous velocity, peak, and the mean systolic gradient. EOA was determined using the continuity equation. Patients with severe paravalvular aortic or mitral valve regurgitation were excluded. The overall peak instantaneous velocity (n=146) was 2.0+/-0.4 m/s with a peak systolic gradient of 17.1+/-7.4 mmHg and a mean gradient of 9.3+/-4.5 mmHg. The mean EOA was 1.82+/ 0.43 cm2 with an indexed EOA of 1.0+/-0.27 cm2/m2. In general, all prostheses showed similar values-with the exception of the Edwards Sapien 23 mm which was associated with higher velocities and peak pressure gradients. CONCLUSION: Our study establishes the normal range for Doppler haemodynamics of four transcatheter aortic valve prostheses. Compared with previously published data of surgically implanted bioprostheses percutaneous valves tend to have similar EOA values but lower mean peak velocities and pressure gradients. In comparison with physiological haemodynamics; however, this new class of heart valves is still associated with a mild obstruction. PMID- 22307869 TI - An unusual presentation of left ventricular assist device thrombus. PMID- 22307870 TI - Effect of obesity and glycemic control on serum lipocalins and insulin-like growth factor axis in type 2 diabetic patients. AB - Obesity, insulin resistance (IR), and progressive decline in pancreatic beta-cell function are major features of type 2 diabetes mellitus (T2DM). Altered adipokines contribute to obesity-induced IR. Hence understanding of adipokines' relation to obesity and glycemic control could be useful to improve disease outcomes. We aimed at determination of serum retinol binding protein-4 (RBP-4), lipocalin-2 (LCN-2), insulin-like growth factor-I (IGF-I), and its binding protein-3 (IGFBP-3) levels in T2DM patients with the impact of obesity and glycemic control on them and their relation to beta-cell function. Serum insulin, RBP-4, LCN-2, IGF-I, and IGFBP-3 estimated by ELISA were examined in 32 T2DM patients and age- and sex-matched 20 healthy controls. Significant elevation was observed in serum RBP-4 (P < 0.001), LCN-2 (P < 0.01), and IGF-I/IGFBP-3 molar ratio (P < 0.05) in T2DM patients in comparison with healthy controls. There was no significant difference in them between nonobese and obese diabetics. However, RBP-4 and IGF/IGFBP-3 molar ratio were higher in uncontrolled than in controlled diabetic patients at P < 0.001 and P < 0.01, respectively. Moreover, RBP-4, LCN 2, and IGF-I/IGFBP-3 molar ratio were negatively correlated with beta-cell function. In conclusion, serum RBP-4 and IGF-I/IGFBP-3 molar ratio but not LCN-2 were prominently elevated with poor glycemic control rather than obesity in T2DM patients. Whereas, declining beta-cell function is associated with elevation of serum RBP-4, LCN-2 as well as IGF-I/IGFBP-3 molar ratio. PMID- 22307871 TI - Assessment by Fibroscan of fibrosis in nonalcoholic fatty liver disease: XL versus M probe? PMID- 22307872 TI - Intense picosecond pulsed electric fields induce apoptosis through a mitochondrial-mediated pathway in HeLa cells. AB - The application of pulsed electric fields (PEF) is emerging as a new technique for tumor therapy. Picosecond pulsed electric fields (psPEF) can be transferred to target deep tissue non-invasively and precisely, but the research of the biological effects of psPEF on cells is limited. Electric theory predicts that intense psPEF will target mitochondria and lead to changes in transmembrane potential, therefore, it is hypothesized that it can induce mitochondrial mediated apoptosis. HeLa cells were exposed to psPEF in this study to investigate this hypothesis. MTT assay demonstrated that intense psPEF significantly inhibited the proliferation of HeLa cells in a dose-dependent manner. Typical characteristics of apoptosis in HeLa cells were observed, using transmission electron microscopy. Loss of mitochondrial transmembrane potential was explored using laser scanning confocal microscopy with Rhodamine-123 (Rh123) staining. Furthermore, the mitochondrial apoptotic events were also confirmed by western blot analysis for the release of cytochrome C and apoptosis-inducing factor from mitochondria into the cytosol. In addition, activation of caspase-3, caspase-9, upregulation of Bax, p53 and downregulation of Bcl-2 were observed in HeLa cells also indicating apoptosis. Taken together, these results demonstrate that intense psPEF induce cell apoptosis through a mitochondrial-mediated pathway. PMID- 22307874 TI - Infections in patients with giant cell arteritis: could hypogammaglobulinemia induced by corticosteroids be a risk factor? Comment on the article by Durand and Thomas. PMID- 22307873 TI - A polymorphism in a let-7 microRNA binding site of KRAS in women with endometriosis. AB - Endometriosis is found in 5-15% of women of reproductive age and is more frequent in relatives of women with the disease. Activation of KRAS results in de novo endometriosis in mice, however, activating KRAS mutations have not been identified in women. We screened 150 women with endometriosis for a polymorphism in a let-7 microRNA (miRNA) binding site in the 3'-UTR of KRAS and detected a KRAS variant allele in 31% of women with endometriosis as opposed to 5% of a large diverse control population. KRAS mRNA and protein expression were increased in cultured endometrial stromal cells of women with the KRAS variant. Increased KRAS protein was due to altered miRNA binding as demonstrated in reporter assays. Endometrial stromal cells from women with the KRAS variant showed increased proliferation and invasion. In a murine model, endometrial xenografts containing the KRAS variant demonstrated increased proliferation and decreased progesterone receptor levels. These findings suggest that an inherited polymorphism of a let-7 miRNA binding site in KRAS leads to abnormal endometrial growth and endometriosis. The LCS6 polymorphism is the first described genetic marker of endometriosis risk. PMID- 22307875 TI - Development of near-isogenic lines and identification of markers linked to auxinic herbicide resistance in wild mustard (Sinapis arvensis L.). AB - BACKGROUND: Auxinic herbicides are widely used for selective control of many broadleaf weeds, e.g. wild mustard. An auxinic-herbicide-resistant wild mustard biotype may offer an excellent model system to elucidate the mechanism of action of these herbicides. Classical genetic analyses demonstrate that the wild mustard auxinic herbicide resistance is determined by a single dominant gene. Availability of near-isogenic lines (NILs) of wild mustard with auxinic herbicide resistance (R) and herbicide susceptibility (S) will help to study the fitness penalty as well as the precise characterization of this gene. RESULTS: Eight generations of backcrosses were performed, and homozygous auxinic-herbicide resistant and auxinic-herbicide-susceptible NILs were identified from BC(8) F(3) families. S plants produced significantly more biomass and seed compared with R plants, suggesting that wild mustard auxinic herbicide resistance may result in fitness reduction. It was also found that the serrated margin of the first true leaf was closely linked to auxinic herbicide resistance. Using the introgressed progeny, molecular markers linked to auxinic herbicide resistance were identified, and a genetic map was constructed. CONCLUSION: The fitness penalty associated with the auxinic herbicide resistance gene may explain the relatively slow occurrence and spread of auxinic-herbicide-resistant weeds. The detection of the closely linked markers should hasten the identification and characterization of this gene. PMID- 22307876 TI - Utilization of general and specialized cardiac care by people with schizophrenia. AB - OBJECTIVE: Whether access to primary and specialist care has an impact on treatment for people with schizophrenia and comorbid cardiac disease is unclear. The objective of this study was to compare use of general health care and specialized cardiac care by people with schizophrenia and by the rest of the population. METHODS: A population-based period-prevalence study was conducted and included adults (N=2,310,391) in Alberta, Canada, by using administrative databases. People with schizophrenia were identified based on billing codes; all others served as the comparator cohort. Multivariable logistic regression analyses were conducted to compare claims for general (general practitioner visits) health care, urgent and emergent (emergency department visits and hospitalizations) health services, and specialized cardiac (cardiologist visits, revascularization) care. RESULTS: Individuals with schizophrenia (N=28,755) had a higher prevalence of coronary artery disease than those without schizophrenia (N=2,281,636) (20% versus 14%) and were more likely than those without schizophrenia to visit a general practitioner more than four times per year (76% versus 47%; adjusted odds ratio [AOR]=3.60, 95% confidence interval [CI]=3.49 3.71). In contrast, individuals with schizophrenia and coronary artery disease were less likely to visit a cardiologist (50% versus 59%; AOR=. 76, 95% CI=.72 .80) or undergo coronary revascularization (6% versus 12%; AOR=. 55, 95% CI=.49 .61). CONCLUSIONS: In this large population-based study, individuals with schizophrenia were less likely to visit cardiologists or undergo revascularization than were people without schizophrenia. Opportunities exist for better assessment and management of cardiovascular disease and risk factors among people with schizophrenia. PMID- 22307877 TI - Development and use of a transition readiness scale to help manage ACT team capacity. AB - OBJECTIVE: This article describes the creation, validation, and use of an assertive community treatment (ACT) Transition Readiness Scale (TRS) to identify clients who may be ready to transition from ACT services. Scale development was prompted by concerns over long stays on ACT teams and the resulting impact on access. METHODS: Data were extracted from a centralized clinical reporting system for all 1,365 persons enrolled for at least 12 months as of August 2008 in the 42 ACT teams in New York City, including 382 clients of eight of those ACT teams. Data in seven domains deemed relevant to transition readiness were used to calculate readiness scores for each client. An algorithm assigned clients to one of three categories: consider for transition, readiness unclear, and not ready. RESULTS: Via the TRS algorithm, of the 1,365 clients, 192 (14%) were assigned to the consider-for-transition group, 382 (28%) to the unclear group, and 791 (58%) to the not ready group. Clinicians on the eight ACT teams categorized 15% of their current clients in the consider-for-transition group, whereas the TRS algorithm classified 18% in this category. Overall, the TRS agreed with the category assigned by ACT team clinicians in 69% of cases. CONCLUSIONS: The TRS may provide ACT teams and program administrators with a tool to identify clients who may be ready to transition to less intensive services, thereby opening scarce slots. Because ACT cases are complex, data summaries can offer useful syntheses of information, particularly when data from several assessments are used to summarize a client's trajectory. PMID- 22307878 TI - Impact of housing and work supports on outcomes for chronically homeless adults with mental illness: LA's HOPE. AB - OBJECTIVE: This study examined the impact of a federally funded housing and employment demonstration program (Los Angeles' Homeless Opportunity Providing Employment [LA's HOPE]) for homeless adults with mental illness. METHODS: The sample included all participants enrolled between July 1, 2004, and May 17, 2005, in one of 18 Los Angeles County community mental health centers offering a state funded program (AB2034) to reduce homelessness among people with serious mental illness. Fifty-six demonstration clients enrolled in three centers received housing and special employment supports. Their outcomes were compared with those of 415 clients enrolled in the county's other 15 AB2034 programs during the same period. Data included demographic characteristics, circumstances at enrollment and in the previous 12 months, and outcomes for at least 13 months after enrollment. Outcomes analyses used propensity score matching. RESULTS: Demonstration clients got and kept housing and worked in paid employment and employment-related activities at rates significantly higher than those of the comparison group. Other than client group, no personal characteristics made any systematic difference to employment outcomes. Several personal characteristics race and ethnicity, preenrollment length of homelessness, and whether the client had a co-occurring substance use disorder-affected housing outcomes independently of client group. CONCLUSIONS: The demonstration provided the structure and resources to help clients achieve better housing and employment outcomes than the comparison group had. The outcomes for LA's HOPE clients suggest that this very challenged population can achieve improved work outcomes if programs devote adequate and appropriate resources to help them. PMID- 22307880 TI - Use of obesity-related care by psychiatric patients. AB - OBJECTIVE: The objective of this study was to assess receipt of obesity care by patients with and without mental illness. METHODS: The sample consisted of 254,051 obese primary care patients surviving through fiscal year (FY) 2006. Administrative data for Veterans Health Administration (VHA) patients who were obese in FY 2002 (body mass index >=30) and received primary care in one of six selected VHA regions were included. Outcomes were receipt of obesity care and weight loss during FY 2002-FY 2006. Covariates included baseline mental illness (major depression, posttraumatic stress disorder, and substance use disorders; ICD-9-CM codes 290-311); psychotropic medications associated with weight gain; comorbidity; and demographic characteristics. RESULTS: Most patients were male (95%), non-Hispanic white (80%), older than 50 (mean+/-SD=61+/-12) with comorbid hypertension (65%) and dyslipidemia (50%). One-fifth (20%) had mental illness, primarily depression (8%) or posttraumatic stress disorder (6%). Ten percent of the sample lost weight, and 7% gained >=10% from baseline weight). Although one third (34%) received obesity care during the study period, receipt of this care was more common among patients with psychiatric diagnoses (46% versus 31%). In multivariable analysis, psychiatric patients prescribed obesogenic psychotropic medications were more likely than other patients to receive obesity care (interaction effect). CONCLUSIONS: VHA efforts to help obese patients manage their weight appeared more common for patients prescribed obesogenic psychotropic medication, especially those with psychiatric diagnoses. The results of this study represent an unusual example in which psychiatric patients were relatively more likely to receive care addressing cardiometabolic risk factors. PMID- 22307881 TI - A randomized controlled trial of supported employment among veterans with posttraumatic stress disorder. AB - OBJECTIVE: Posttraumatic stress disorder (PTSD) is a potentially disabling mental illness that can cause occupational dysfunction. Although vocational rehabilitation is often prescribed for patients with PTSD, standard vocational services are far from adequate in helping them obtain and maintain competitive employment. This study is the first to examine the outcome of evidence-based supported employment for veterans with PTSD. METHODS: Unemployed veterans with PTSD were randomly assigned to either individual placement and support (IPS) supported employment (N = 42) or a Veterans Health Administration Vocational Rehabilitation Program (VRP) treatment as usual (N = 43). Employment rates and occupational outcomes were followed for 12 months. RESULTS: During the 12-month study, 76% of the IPS participants gained competitive employment, compared with 28% of the VRP participants (number needed to treat = 2.07; chi(2) = 19.84, df = 1, p<.001). Veterans assigned to IPS also worked substantially more weeks than those assigned to VRP (42% versus 16% of the eligible weeks, respectively; Mann Whitney z test p<.001) and earned higher 12-month income (mean +/- SD income of $9,264 +/- $13,294 for IPS versus $2,601 +/- $6,009 for VRP; Mann-Whitney z test p<.001) during the 12-month period. CONCLUSIONS: Veterans with PTSD who received IPS were 2.7 times more likely to gain competitive employment than those who received VRP. Because work is central to recovery, these results should assist stakeholders in planning improved services for veterans with PTSD. PMID- 22307882 TI - Disparities in cancer care: Are we making progress?: a look at how researchers and organizations are working to reduce cancer health disparities. PMID- 22307883 TI - Scientists target cholesterol to treat brain tumors. PMID- 22307884 TI - Depression in Latina survivors of breast cancer affects preventive health screening. PMID- 22307885 TI - Multiplicity of genes for aromatic ring-hydroxylating dioxygenases in Mycobacterium isolate KMS and their regulation. AB - Mycobacterium sp. strain KMS has bioremediation potential for polycyclic aromatic hydrocarbons (PAHs), such as pyrene, and smaller ring aromatics, such as benzoate. Degradation of these aromatics involves oxidation catalyzed by aromatic ring-hydroxylating dioxygenases. Multiple genes encoding dioxygenases exist in KMS: ten genes encode large-subunits with homology to phenylpropionate dioxygenase genes, sixteen pairs of adjacent genes encode alpha- and beta subunits of dioxygenase and two genes encode beta-subunits. These genes include orthologs of nid genes essential for degradation of multi-ring PAHs in M. vanbaalenii isolate PYR-1. The multiplicity of genes in part is explained by block duplication that results in two or three copies of certain genes on the chromosome, a linear plasmid, and a circular plasmid within the KMS genome. Quantitative real-time PCR showed that four dioxygenase beta-subunit nid genes from operons with almost identical promoter sequences otherwise unique in the genome were induced by pyrene to similar extents. No induction occurred with benzoate. Unlike isolate PYR-1, isolate KMS has an operon specifying benzoate catabolism and the expression of the alpha-subunit dioxygenase gene was activated by benzoate but not pyrene. These studies showed that isolate KMS had a genome well adapted to utilization of different aromatic compounds. PMID- 22307886 TI - IgA anti-tTG antibodies in children with severe short stature without gastrointestinal manifestations. PMID- 22307887 TI - Pay attention to esophageal mucosa in achalasia. PMID- 22307888 TI - Trichlorosilane mediated asymmetric reductions of the C=N bond. AB - Chiral amines are key components in numerous bioactive molecules. The development of efficient and economical ways to access molecules containing this functional group still remains a challenge at the forefront of synthetic chemistry. Of the methods that do exist, the trichlorosilane mediated organocatalytic reduction of ketimines offers significant potential as an alternative strategy. In this perspective, we wish to highlight the progress made in the past decade in this field and offer a direct quantitative comparison to transition-metal mediated process. PMID- 22307889 TI - Growth hormone response induced by a respiratory muscle endurance training in healthy subjects. AB - To date, the large majority of studies evaluating growth hormone (GH) response to acute physical exercise has been performed involving gross muscle groups. To the best of our knowledge, none has evaluated the effects of a respiratory muscle endurance training (RMET) on hormonal secretions, particularly on GH release, though some respiratory devices have been widely used in athletes to train respiratory muscles and to improve cardiopulmonary function and physical performance. 8 healthy men underwent an incremental progressive RMET protocol of 11 daily sessions, obtained through the use of a specifically designed respiratory device (Spiro Tiger(r)). The 12th session of RMET (15 min duration: 1 min at a respiration rate of 28 acts/min, 5 min at 32 acts/min, 5 min at 34 acts/min, 4 min at 36 acts/min) was associated with blood samplings for determination of GH, cortisol, ghrelin, glucose, and lactate (LA) levels. GH and cortisol responses significantly increased after a 15-minute RMET session, which, in contrast, inhibited ghrelin secretion. There was a minimal, though significant, increase in LA levels with a significant elevation in glycemia. A 15 minute RMET session, administered after a 11-days incremental progressive RMET protocol, was capable of stimulating GH and cortisol release and suppressing ghrelin secretion. Optimization of incremental progressive RMET protocols would be important to maximize the positive chronic effects of this intervention on somatotropic function and muscle performance. PMID- 22307890 TI - Delusion proneness and emotion appraisal in individuals with high psychosis vulnerability. AB - Evidence suggests that emotional processes play an important role in the development of delusions. The aim of the present study was to investigate emotion appraisal in individuals with high and low psychosis proneness. We compared 30 individuals who experienced a transient psychotic episode followed by a complete remission with 30 healthy control volunteers. The participants received the Peters et al. Delusion Inventory (PDI) and the Scherer's Emotion Appraisal Questionnaire. We also assessed the IQ and the severity of depressive and anxiety symptoms. Results revealed that individuals with high psychosis proneness displayed increased PDI scores and more pronounced anxiety compared with individuals with low psychosis proneness. There was a specific pattern of emotion appraisal in individuals with high psychosis proneness. In the case of fear, they achieved higher scores for external causality and immorality, and lower scores for coping ability and self-esteem compared with individuals with low proneness. The PDI scores were weakly related to external causality (r = 0.41) and self esteem (r = -0.37). In the case of sadness and joy, no emotion appraisal differences were found between participants with low and high proneness. These results suggest that individuals who had a history of psychotic breakdown and therefore exhibit high psychosis proneness display an altered appraisal of fear, emphasizing external circumstances, feeling less power to cope and experience low self-esteem. KEY PRACTITIONER MESSAGE: Patients remitted from a transient psychotic episode still exhibit milder forms of delusion proneness. Emotion appraisal for fear is related to delusion proneness. Clinicians should pay a special attention to self-esteem and attribution biases in psychosis-prone individuals. PMID- 22307891 TI - Effects of disorder on the optical properties of CVD grown polycrystalline graphene. AB - We explore the effects of crystallite size (L(a)) on the linear and non-linear optical properties of chemical vapor deposition grown polycrystalline graphene. The pi-plasmon resonance present at ~4.75 eV (~260 nm) in the optical absorption spectrum of graphene follows the empirical relationship lambda(pi) = 250.5 nm + 89.5 nm(2)/L(a), where lambda(pi) represents the pi-plasmon wavelength. Furthermore, our Z-scan studies reveal that the crystallite size significantly changes the saturation intensity in CVD grown graphene. Notably, in comparison to epitaxial graphene layers grown on SiC wafers which exhibit a photogenerated carrier lifetime of few picoseconds, we find that the photogenerated carriers in our CVD grown graphene can exhibit lifetimes as long as nanoseconds. PMID- 22307892 TI - Cyclization of aromatic propargyl alcohol with a thiophene group yielding naphthothiophene aldehyde induced by a ruthenium complex. AB - The reactions of [Cp(PPh(3))(2) RuCl] (Cp=cyclopentadienyl) with phenyl propargylic alcohol 1a, with a 3-thiophene group, are explored. The carbene complex 2a, obtained exclusively from this reaction at low temperature, contains the naphthothiophene group, which is formed through a new cyclization process between the thiophene group and the inner carbon of the triple bond. Details of this process have been revealed by conducting the reaction at room temperature, affording the allenylidene complex 3a as a side product. Complex 3a is not converted into 2a, indicating that the cyclization takes place while the triple bond is pi coordinated to the metal center. Complex 2a reacts with oxygen in the presence of NEt(3) at room temperature to afford, in high yield, naphthothiophene aldehyde 4a, ONEt(3), OPPh(3), and [Cp(PPh(3))(2)RuCl]. Molecular O(2) is likely activated by coordination to the metal center when one of the phosphane ligands dissociates. Then, NEt(3) promotes the oxygenation process by reacting with the coordinated O(2) to afford ONEt(3) and possibly an unobserved oxo-carbene complex. Coupling of the oxo and carbene ligands then yields 4a and [Cp(PPh(3))(2) RuCl] in CHCl(3). In a solvent system containing MeOH, the oxygenation reaction affords a mixture of 4a and naphthothiophene ester 5a-1. The reactions of [Cp(dppf)RuCl] (dppf=1,1'-bis(diphenylphosphino)ferrocene) with 1a, also afford the carbene complex 2a', 4a, and 5a, which have been characterized by X-ray diffraction analyses. For the phenyl propargylic alcohol 1b, with a 2 thiophene substituent, different naphthothiophene aldehyde and ester compounds are also obtained in high yields through a similar cyclization process followed by oxygenation under mild conditions. PMID- 22307893 TI - Prognostic value of 18F-FDG PET/CT in patients with squamous cell carcinoma of the tonsil: comparisons of volume-based metabolic parameters. AB - BACKGROUND: The prognostic significance of volume-based metabolic parameters measured by (18)F-fluorodeoxyglucose positron emission tomography/CT ((18) F-FDG PET/CT) is not established. We evaluated the prognostic value of metabolic parameters in patients with squamous cell carcinoma (SCC) of the tonsil. METHODS: We enrolled a total of 69 patients with SCC of the tonsil who underwent pretreatment (18)F-FDG PET/CT. We measured maximum standardized uptake value (SUV(max)), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and asymmetry indices (of SUV(max), MTV, and TLG). The prognostic significance of these parameters and clinical variables was assessed by Cox proportional hazards regression analysis. RESULTS: Multivariate analyses with adjustments for age, sex, and American Joint Committee on Cancer stage showed that only TLG (hazard ratio = 1.020, 95% confidence interval 1.003-1.037, p = .023) was an independent predictive factor associated with decreased overall survival. CONCLUSION: TLG is a significant independent metabolic prognostic factor for overall survival in patients with SCC of the tonsil. PMID- 22307894 TI - Occurrence and distribution of selected pharmaceuticals and personal care products in aquatic environments: a comparative study of regions in China with different urbanization levels. AB - PURPOSE: We analyzed and compared the distributions of 13 target pharmaceuticals in different water samples from the Hangzhou metropolitan area and Linan County, Southeast China. METHODS: Sampling was conducted in five hospitals, two wastewater treatment plants (WWTPs), and Qiantang River. Samples were concentrated by solid-phase extraction and PPCP concentrations were determined by UPLC-MS/MS. RESULTS AND DISCUSSION: Trimethoprim, erythromycin A dihydrate, norfloxacin, ofloxacin, diclofenac sodium, and atenolol were the most frequently detected pharmaceuticals in hospital effluents. Most of the pharmaceutical concentrations in hospital effluents were higher than those in the WWTP influents. Although both WWTPs adopt the anaerobic-aerobic-anoxic treatment process, the removal rates for pharmaceuticals, such as trimethoprim and diclofenac sodium, were completely different. Meanwhile, erythromycin A dihydrate, ofloxacin, penicillin-G, cephalexin, cefazolin, ibuprofen, and diclofenac sodium were detected in Qiantang River. CONCLUSIONS: These results indicate that hospitals are more concentrated sources of pharmaceuticals than WWTPs, and the WWTPs are not the only route of entry of pharmaceuticals into aquatic environments in these two regions. PMID- 22307895 TI - Exposure assessment of pesticides in a shallow groundwater of the Tagus vulnerable zone (Portugal): a multivariate statistical approach (JCA). AB - PURPOSE: To assess groundwater exposure to pesticides, in agricultural areas of 'Ribatejo' region (Portugal), and the influence of some key factors in that exposure, field, laboratory and modelling studies were carried out. METHODS: The study was performed in maize, potato, sugar beet, tomato and vegetables agricultural areas, located in a shallow aquifer, with pesticides use and, in most cases, with irrigation practices. Pesticides used in the studied agricultural areas and having leaching potential were selected, being considered also other pesticides included in priority lists, defined in Europe. Evaluation of groundwater exposure to pesticides was carried out by successively: (1) groundwater sampling in seven campaigns over the period 2004-2006; (2) pesticide analysis [including isolation and concentration from the groundwater samples and further determination by gas chromatography-mass spectrometry (GC-MS) of 14 herbicides, four insecticides and two metabolites]; and (3) analysis and discussion of the results by applying joint correspondence analysis (JCA). RESULTS: From the 20 pesticides and metabolites selected for the study, 11 were found in groundwater. Pesticides and metabolites most frequently detected were atrazine, alachlor, metolachlor, desethylatrazine, ethofumesate, alpha endosulfan, metribuzine, lindane and beta-endosulfan. The results showed that groundwater exposure to pesticides is influenced by local factors-either environmental or agricultural, as precipitation, soil, geology, crops and irrigation practices. Spring and autumn were more associated with the detection of pesticides being more likely to observe mixtures of these compounds in a groundwater sample in these transition seasons. CONCLUSIONS: This work evidences the importance of models, which evaluate pesticides environmental behaviour, namely their water contamination potential (as Mackay multicompartimental fugacity model) and, specially, groundwater contamination potential (as GUS and Bacci and Gaggi leaching indices), in pesticide selection. Moreover, it reveals the importance to adapt proper statistical methods according to level of left censored data. Using JCA was still possible to establish relations between pesticides and their temporal trend in a case study where there were more than 80% of data censored. This study will contribute to the Tagus river basin management plan with information on the patterns of pesticide occurrence in the alluvial aquifer system. PMID- 22307896 TI - Environmental metabolites of fluoroquinolones: synthesis, fractionation and toxicological assessment of some biologically active metabolites of ciprofloxacin. AB - BACKGROUND, AIM, AND SCOPE: Biowastes produced by humans and animals are routinely disposed of on land, and concern is now growing that such practices provide a pathway for fluoroquinolone (FQs) antibacterial agents and their environmental metabolites (FQEMs) to contaminate the terrestrial environment. The focus of concern is that FQs and FQEMs may accumulate in amended soils to then adversely impact on the terrestrial environment. One postulated impact is the development of a selective environment in which FQ-resistant bacteria may grow. To find evidence in support of an accumulation of antibacterial-like activity, it was first necessary to establish whether any biologically active FQEMs could be synthesized by physicochemical factors that are normally present in the environment. However, many FQEMs are not commercially available to be used as standards in such studies. FQEMs were therefore synthesized using well-defined processes. They were subsequently analyzed using spectroscopy (UV-vis) and high performance liquid chromatography with mass spectral detection. The antibacterial like activities of fractionated FQEMs were then assessed in novel bacterial growth inhibition bioassays, and results were compared to those obtained from instrumental analyses. MATERIALS AND METHODS: Parent FQs were either exposed to sunlight or were synthesized using defined aerobic microbial (Mycobacterium gilvum or a mixed culture derived from an agricultural soil) fermentation processes. Mixtures of FQEMs derived from photo- and (intracellular) microbial processes were isolated by preparative chromatography and centrifugation techniques, respectively. Mixtures were subsequently fractionated using analytical high-performance thin layer chromatography (HPTLC), and excised analytes were tested in bioautography assays for their antibacterial-like activities. Two bacteria, Escherichia coli (E. coli) and Azospirillum brasilense (A. brasilense) were used as reporter organisms in testing FQ standards and any subtle differences between biologically active FQEMs of ciprofloxacin (CF). RESULTS AND DISCUSSION: FQEMs produced in the photo-synthetic process had UV-vis profiles that were indistinguishable from the parent FQs, and yet mass spectral data revealed the presence of N-formylciprofloxacin (FCF). In contrast, the UV vis profiles of FQEMs synthesized by M. gilvum and a mixed culture of microorganisms had UV-vis profiles that were similar to one another and markedly different to the parent fluoroquinolones. Mass spectral studies confirmed the presence of FCF and N-acetylciprofloxacin in both microbial ferments. In addition, a photo-FQEM (Cp 6), three M. gilvum FQEMs (Cm 5, Cm 8, and Cm 10) and a mixed culture FQEM (Cs 6) of CF and many other FQEMs of CF, norfloxacin (NF), and enrofloxacin (EF) were fractionated using HPTLC, although their identities have yet to be confirmed. Differences between bioautography results were obtained when E. coli or A. brasilense were used as reporter organisms. Parent FQs (CF and EF) and the FQEMs of CF (Cp 6, Cm 8, and Cs 6) displayed antibacterial-like activity when using E. coli as the reporter organism. In contrast, A. brasilense was insensitive to parent CF and sensitive to EF and all tested FQEMs of CF. Results are consistent with photo- and microbial processes modifying CF in different ways, with the latter changing the UV-vis chromophores. It can be inferred that a lack of detection of analytes (especially photo-FQEMs) when using UV-vis does not necessarily indicate an absence of analyte. Additionally, similarities between the UV-vis profiles of FQEMs extracted from the (monoculture) M. gilvum and the mixed culture microbial aerobic ferments are consistent with similar processes operating in both ferments. Results of HPTLC and bioautography studies revealed that mixtures of (photo- and microbial) FQEMs could be fractionated into individual components. CONCLUSIONS: Bioactive FQEMs of ciprofloxacin, as a representative FQ, can be synthesized by photo- and microbial processes, and their detection required the use of both instrumental and bioautography analytical techniques. It is likely that such FQEMs will also be present on agricultural land that has been repeatedly amended with FQ contaminated biosolids. RECOMMENDATIONS AND PERSPECTIVES: The use of instrumental analytical techniques alone and especially photometric detection techniques will underestimate antibacterial-like activities of FQEMs. Moreover, the extraction technique(s) and the selected toxicological endpoint(s) require careful consideration when assessing bioactivity. It is therefore recommended that instrumental analytical techniques and several bioautography assays be performed concurrently, and bioautography assays should use a variety of reporter organisms. Two types of bacterial growth bioassays are recommended in any assessment of antibacterial-like activity derived from CF (and possibly from other FQs). A standardized E. coli bioassay should be used as a general screening procedure to facilitate intra- and inter-laboratory exchange of data. Additionally, soil-specific (region-specific) growth inhibition bioassays should be undertaken using several species of endemic soil bacteria. It is likely that the two sets of data will be useful in future risk assessment processes. PMID- 22307897 TI - Development of a country-specific CO2 emission factor for domestic anthracite in Korea, 2007-2009. AB - INTRODUCTION: Korea has been making efforts to reduce greenhouse gas (GHG) emissions, including a voluntary commitment to the target of a 30% reduction, based on business-as-usual of the total GHG emission volume, by 2020; 2006 IPCC Guidelines provided default values, applying country-specific emission factors was recommended when estimating national greenhouse gas emissions. RESULTS AND DISCUSSION: This study focused on anthracite produced in Korea in order to provide basic data for developing country-specific emission factor. This study has estimated CO(2) emission factors to use worksheet of which five steps consisted according to the fuel analysis method. CONCLUSION: As a result, the average of net colorific value for 3 years (2007~2009) was 4,519 kcal/kg, and the CO(2) emission factor was calculated to be 111,446 kg/TJ, which is about 11.8% lower than the 2006 IPCC guidelines default value, and about 7.9% higher than the US EPA emission factor. PMID- 22307898 TI - Optimization of electrocoagulation process for the simultaneous removal of mercury, lead, and nickel from contaminated water. AB - PURPOSE AND AIM: The present study provides an optimization of electrocoagulation process for the simultaneous removal of heavy metals such as mercury, lead, and nickel from water. In doing so, the thermodynamic, adsorption isotherm and kinetic studies were also carried out. MATERIALS AND METHODS: Magnesium alloy, magnesium, aluminum, and mild steel sheet of size 2 dm(2) were used as anode and galvanized iron as cathode. To optimize the maximum removal efficiency, different parameters like effect of initial concentration, effect of temperature, pH, and effect of current density were studied. Mercury-, lead-, and nickel-adsorbed magnesium hydroxide coagulant was characterized by SEM and EDAX. RESULTS: The results showed that the maximum removal efficiency was achieved for mercury, lead, and nickel with magnesium alloy as anode and galvanized iron as cathode at a current density of 0.15 A/dm(2) and pH of 7.0. The adsorption of mercury, lead, and nickel are preferably fitting the Langmuir adsorption isotherm suggests monolayer coverage of adsorbed molecules. The adsorption process follows second order kinetics. Temperature studies showed that adsorption was endothermic and spontaneous in nature. CONCLUSIONS: The magnesium hydroxide generated in the cell removes the heavy metals present in the water and reduces to a permissible level, making it drinkable. PMID- 22307899 TI - Microwave-assisted synthesis of hydroxyapatite for the removal of lead(II) from aqueous solutions. AB - PURPOSE: This study has the objective to evaluate the lead(II) removal capacity of hydroxyapatite powder synthesized by microwave as an alternative method to decrease production time and cost. METHODS: Hydroxyapatite (HA) was synthesized by a microwave-assisted precipitation method using calcium nitrate and ammonium hydrogen phosphate as calcium and phosphorus sources, respectively. X-ray diffraction and Fourier transform infrared results clearly revealed that the resulting powder was HA with high purity and crystallinity. The obtained powder was used for the removal of lead(II) from aqueous solutions. The effects of pH, amount of adsorbent, initial lead(II) concentration, and contact time were studied in batch experiments. RESULTS: In the adsorption experiments, maximum lead(II) retention was obtained at pH 6. Adsorption equilibrium was established after 40 min. It was found that the adsorption of lead(II) on HA was correlated well (R (2) = 0.958) with the Freundlich equation for the concentration range studied. Both ion exchange and adsorption process were thought to exist in the removal process. CONCLUSIONS: This study indicates that easily and rapidly synthesized HA by microwave-assisted precipitation method could be used as an efficient adsorbent for removal of lead(II) from aqueous solutions. PMID- 22307901 TI - Perspectives from the French workshop on the development and validation of biomarkers and bioassays for the monitoring of aquatic environments. PMID- 22307902 TI - Student ratings of selection factors for PsyD programs. AB - OBJECTIVES: To explore which factors doctor of psychology (PsyD) students feel are important to consider when selecting a PsyD program. DESIGN: This article analyzes the survey responses of 394 enrolled PsyD students and 17 directors of clinical training (DCTs), in which the respondents rated the importance of 18 factors in program selection to understand what qualities PsyD students and DCTs value in a PsyD program. Students were also asked to assess how their program fared on the same 18 dimensions. RESULTS: Results indicated that participants rated the program's structure, tone, and reputed quality of training as the most important factors in program selection (M's of 4.13 to 4.54 on a 5-point scale). Additionally, students rated their current program as high in quality on the same factors that they felt were most important in program selection (r's ranging from .15 to .37). CONCLUSIONS: PsyD students rated a program's structure, tone, and reputation as particularly important factors to consider in selecting a program. Students' quality ratings were used to determine the top 5 programs for each of the factors assessed in the study. PMID- 22307903 TI - Gastrointestinal stromal tumor arising in an ileal duplication: report of a case. AB - This report presents the extremely rare case of an adult patient who presented with peritonitis caused by the perforation of an ileal duplication, associated with a gastrointestinal stromal tumor (GIST) arising within the duplication. A 70 year-old female was admitted to the hospital with lower abdominal pain. Abdominal computed tomography showed free air in the peritoneal cavity. An emergency laparotomy was performed, presuming diffuse peritonitis caused by a perforation of the gastrointestinal tract. The surgical findings showed that the peritonitis was caused by the perforation of an ileal duplication, 90 cm proximal to the ileocecal valve, with an extrinsic tumor protruding from the duplication. A segmental resection of the ileum-including the tumor and ileal duplication-was performed. Histopathology showed that the tumor was composed of spindle-shaped and epithelioid cells. The tumor was immunohistochemically positive for KIT, with a deletion mutation spanning the intron 10-exon 11 boundary. Accordingly, a diagnosis was made of a GIST arising within a duplication of the ileum. Duplications of the alimentary tract are encountered only occasionally in adults. Although quite rare, malignant change should therefore be considered as a possible complication when a solid portion is observed within a duplication of the alimentary tract. PMID- 22307904 TI - Spontaneous pneumothorax in a patient with dendriform pulmonary ossification: report of a case. AB - We report herein the rare case of a patient with dendriform pulmonary ossification (DPO) who developed spontaneous pneumothorax. A 33-year-old male with a history of bronchial asthma presented with pneumothorax of the left lung. An intraoperative inspection revealed no findings of bullae in the entire left lung, but inflammatory pleural changes were identified on the interlobular surface of the left lower lobe. In addition, hard, twig-like configurations were clearly palpable in the subpleural parenchyma and were resected. A histological examination showed acicular bone formations containing myeloid tissue and marrow fat in the lung. DPO was thus diagnosed, and the bony spines were considered to have caused a rupture of the elastic fiber layer of the visceral pleura. DPO may thus have been directly responsible for the pneumothorax in this case. PMID- 22307905 TI - Intestinal obstruction caused by colonic metastasis from intrahepatic cholangiocarcinoma 6 years after removal of the primary tumor: report of a case. AB - We report a case of intestinal obstruction caused by metastasis that manifested 6 years after surgery for intrahepatic cholangiocarcinoma (ICC). The patient, a 57 year-old man, had undergone resection of the hepatic left lobe, Spiegel lobe, and extrahepatic bile duct, following which histopathological examination had confirmed the diagnosis of ICC and that the resection margins were free from disease. There had been no signs of recurrence until an increase in the CA19-9 level was detected 6 years later. Colonoscopy revealed an ulcer-like lesion and stenosis at the level of the hepatic flexure. The patient was subsequently admitted to our hospital with abdominal pain and underwent right hemicolectomy with partial resection of hepatic segment V. Based on the immunohistological finding that the expression pattern of cytokeratins and mucins was consistent with ICC origin rather than colon cancer origin, we diagnosed colon metastasis from ICC. PMID- 22307906 TI - Map kinase phosphatase 5 protects against sepsis-induced acute lung injury. AB - Mitogen-activated protein kinases (MAPKs) play a critical role in inflammation. Although activation of MAPK in inflammatory cells has been studied extensively, much less is known about the inactivation of these kinases. MAPK phosphatase 5 (MKP5) is a member of the dual-specificity phosphatase family that dephosphorylates activated MAPKs. Here we report that MKP5 protects sepsis induced acute lung injury. Mice lacking MKP5 displayed severe lung tissue damage following LPS challenge, characterized with increased neutrophil infiltration and edema compared with wild-type (WT) controls. In response to LPS, MKP5-deficient macrophages produced significantly more inflammatory factors including inflammatory cytokines, nitric oxide, and superoxide. Phosphorylation of p38 MAPK, JNK, and ERK were enhanced in MKP5-deficient macrophages upon LPS stimulation. Adoptive transfer of MKP5-deficient macrophages led to more severe lung inflammation than transfer of WT macrophages, suggesting that MKP5-deficient macrophages directly contribute to acute lung injury. Taken together, these results suggest that MKP5 is crucial to homeostatic regulation of MAPK activation in inflammatory responses. PMID- 22307907 TI - A brief overview of mouse models of pulmonary arterial hypertension: problems and prospects. AB - Many chronic pulmonary diseases are associated with pulmonary hypertension (PH) and pulmonary vascular remodeling, which is a term that continues to be used to describe a wide spectrum of vascular abnormalities. Pulmonary vascular structural changes frequently increase pulmonary vascular resistance, causing PH and right heart failure. Although rat models had been standard models of PH research, in more recent years the availability of genetically engineered mice has made this species attractive for many investigators. Here we review a large amount of data derived from experimental PH reports published since 1996. These studies using wild-type and genetically designed mice illustrate the challenges and opportunities provided by these models. Hemodynamic measurements are difficult to obtain in mice, and right heart failure has not been investigated in mice. Anatomical, cellular, and genetic differences distinguish mice and rats, and pharmacogenomics may explain the degree of PH and the particular mode of pulmonary vascular adaptation and also the response of the right ventricle. PMID- 22307908 TI - Vascular endothelial growth factor enhances macrophage clearance of apoptotic cells. AB - Efficient clearance of apoptotic cells from the lung by alveolar macrophages is important for the maintenance of tissue structure and function. Lung tissue from humans with emphysema contains increased numbers of apoptotic cells and decreased levels of vascular endothelial growth factor (VEGF). Mice treated with VEGF receptor inhibitors have increased numbers of apoptotic cells and develop emphysema. We hypothesized that VEGF regulates apoptotic cell clearance by alveolar macrophages (AM) via its interaction with VEGF receptor 1 (VEGF R1). Our data show that the uptake of apoptotic cells by murine AMs and human monocyte derived macrophages is inhibited by depletion of VEGF and that VEGF activates Rac1. Antibody blockade or pharmacological inhibition of VEGF R1 activity also decreased apoptotic cell uptake ex vivo. Conversely, overexpression of VEGF significantly enhanced apoptotic cell uptake by AMs in vivo. These results indicate that VEGF serves a positive regulatory role via its interaction with VEGF R1 to activate Rac1 and enhance AM apoptotic cell clearance. PMID- 22307909 TI - Mesenchymal stem cell-conditioned media recovers lung fibroblasts from cigarette smoke-induced damage. AB - Cigarette smoking causes apoptotic death, senescence, and impairment of repair functions in lung fibroblasts, which maintain the integrity of alveolar structure by producing extracellular matrix (ECM) proteins. Therefore, recovery of lung fibroblasts from cigarette smoke-induced damage may be crucial in regeneration of emphysematous lung resulting from degradation of ECM proteins and subsequent loss of alveolar cells. Recently, we reported that bone marrow-derived mesenchymal stem cell-conditioned media (MSC-CM) led to angiogenesis and regeneration of lung damaged by cigarette smoke. In this study, to further investigate reparative mechanisms for MSC-CM-mediated lung repair, we attempted to determine whether MSC CM can recover lung fibroblasts from cigarette smoke-induced damage. In lung fibroblasts exposed to cigarette smoke extract (CSE), MSC-CM, not only inhibited apoptotic death, but also induced cell proliferation and reversed CSE-induced changes in the levels of caspase-3, p53, p21, p27, Akt, and p-Akt. MSC-CM also restored expression of ECM proteins and collagen gel contraction while suppressing CSE-induced expression of cyclooxygenase-2 and microsomal PGE(2) synthase-2. The CSE-opposing effects of MSC-CM on cell fate, expression of ECM proteins, and collagen gel contraction were partially inhibited by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. In rats, MSC-CM administration also resulted in elevation of p-Akt and restored proliferation of lung fibroblasts, which was suppressed by exposure to cigarette smoke. Taken together, these data suggest that MSC-CM may recover lung fibroblasts from cigarette smoke induced damage, possibly through inhibition of apoptosis, induction of proliferation, and restoration of lung fibroblast repair function, which are mediated in part by the PI3K/Akt pathway. PMID- 22307910 TI - Editorial: state-of-the-art reviews in industrial biotechnology. PMID- 22307913 TI - From bench to market: life science patents in Europe. PMID- 22307916 TI - Therapeutic plasma exchange in Streptococcus pneumoniae-associated hemolytic uremic syndrome: a case report. AB - Streptococcus pneumoniae-associated hemolytic uremic syndrome (pHUS) is an atypical form of HUS associated with microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. Although less common than diarrhea associated HUS, incidence appears to be increasing. We report a case of a child with pHUS who underwent a course of therapeutic plasma exchange (TPE) and had complete recovery. This report adds to the existing literature supporting TPE in cases of pHUS. PMID- 22307917 TI - Drug-related adverse events may predict efficacy in sorafenib therapy for hepatocellular carcinoma. PMID- 22307918 TI - Interactions between the root pathogen Rhizoctonia solani AG-8 and acetolactate synthase-inhibiting herbicides in barley. AB - BACKGROUND: The widespread acceptance of reduced-tillage farming in cereal cropping systems in the Pacific Northwest of the United States has resulted in increased use of herbicides for weed control. However, soil residual concentrations of widely used imidazalone herbicides limit the cultivation of barley, which is more sensitive than wheat. In addition, increased severity of the root rot disease caused by Rhizoctonia solani is associated with reduction in tillage. Many crops exhibit altered disease responses after application of registered herbicides. In this study, the injury symptoms in barley caused by sublethal rates of two acetolactate synthase (ALS)-inhibiting herbicides, imazamox and propoxycarbazone-sodium, were assessed in factorial combinations with a range of inoculum concentrations of the root rot pathogen Rhizoctonia solani AG-8. RESULTS: Both herbicides and pathogen had negative impacts on plant growth parameters such as root and shoot dry weight, shoot height and first leaf length, and interactions between pathogen and herbicide were detected. CONCLUSIONS: The results suggested that sublethal rates of herbicides and R. solani could alter severity of injury symptoms, possibly owing to the herbicide predisposing the plant to the pathogen. PMID- 22307919 TI - Comparability of cancer identification among Death Registry, Cancer Registry and Hospital Discharge Registry. AB - Registry-based cancer incidence and mortality data are widely used for etiologic research, cancer control and health care monitoring and planning. The complete coverage of all cases is the key criteria of data quality but it is difficult to assess because the alternative sources of data may be flawed. The aim of our study was to examine, at a nationwide level, the completeness of the Swedish Cancer Registry (CR) regarding persons who died of cancer, based on the Cause of Death Registry (DR), and using the Hospital Discharge Registry (HDR) as an additional source of data. Individuals who died of cancer from years 1999 through 2008 recorded in DR were linked to CR and HDR. A total of 190,692 individuals were identified from DR with cancer as the underlying cause of death; the mean identification rate of concordant cancer in CR was 79.8%, depending on tumor site and age at death. Breast, bladder and prostate cancers showed the highest rate of identification, whereas bone, liver and pancreatic cancers showed the lowest rate of identification. CR had no records on 10.6% of cancer cases recorded in DR. Similarly, the identification rate in HDR was 84.5% for concordant cancer and with 9.6% of cases missing. Neither source reported cancers for 3.4% of cancer cases recorded in DR. In conclusion, some 10% of cancer deaths had no cancer records in CR or in HDR, and 3.4% were missing in both sources. The identification rate depended on tumor site, age at death and, to some extent, death outside hospital. PMID- 22307920 TI - Characterization of DcsC, a PLP-independent racemase involved in the biosynthesis of D-cycloserine. AB - The biosynthetic gene cluster responsible for the generation of the antibiotic D cycloserine (DCS) has recently been disclosed. One of the putative enzymes described was DcsC, which showed a high degree of homology to diaminopimelate epimerase (DapF). Based on this homology, the activity of DcsC was presumed to be the racemization of O-ureido-L-serine, a proposed intermediate in DCS biosynthesis. Here we describe the cloning, overexpression and characterization of this enzyme. Using synthetic standards we show that DcsC is a racemase that operates on both O-ureido-L- and D-serine, and that it employs a two-base mechanism, with a thiolate-thiol pair in the active site. The activity of this enzyme was shown to be optimal at pH ~ 7.8, with a similar k(cat)/K(M) ratio in both the L->D direction and D->L direction. Activity was abolished with thiol inactivating reagents such as iodoacetamide and Hg(2+) ions. Further evidence for a thiolate in the active site was obtained through the use of an epoxide containing substrate analogue (6), which became covalently attached to the enzyme. PMID- 22307921 TI - Multicultural challenges in the delivery of anxiety treatment. PMID- 22307922 TI - Etiologic relationships between anxiety and dimensions of maladaptive perfectionism in young adult female twins. AB - BACKGROUND: Theory and research suggest that maladaptive perfectionism, specifically, concerns about mistakes (CM) and doubts about actions (DA), may be important etiologic and maintenance mechanisms for anxiety and its disorders. However, no studies speaking directly to the origins of the relationship, i.e. what etiologic factors underlie the phenotypic association between anxiety and maladaptive perfectionism, exist. The current study aimed to address this gap in the literature by exploring genetic and environmental relationships between anxiety symptoms and maladaptive perfectionism. METHODS: The sample consisted of 292 young adult same-sex female twins from the Michigan State University Twin Registry. Anxiety symptoms were assessed by the State Trait Anxiety Inventory Trait version and an anxiety problems scale derived from the Young Adult Self Report. Maladaptive perfectionism was measured using the CM and DA subscales of the Frost Multidimensional Perfectionism Scale. RESULTS: Anxiety and maladaptive perfectionism were both moderately heritable, with estimates ranging from. 45 to .66. Moreover, multivariate analyses revealed that genetic factors were primarily responsible for associations between anxiety and maladaptive perfectionism (r(g) =.59-.88). CONCLUSION: This is the first study to demonstrate the role of genetic factors in the relationship between anxiety and maladaptive perfectionism. Future studies are needed to uncover the specific biologic and genetic factors that contribute to this relationship and to evaluate whether maladaptive perfectionism represents an intermediate trait or risk factor for anxiety. PMID- 22307923 TI - Allelic clustering and ancestry-dependent frequencies of rs6232, rs6234, and rs6235 PCSK1 SNPs in a Northern Ontario population sample. AB - The PCSK1 (proprotein convertase subtilisin/kexin type 1) locus encodes proprotein convertase 1/3, an endoprotease that converts prohormones and proneuropeptides to their active forms. Spontaneous loss-of-function mutations in the coding sequence of its gene have been linked to obesity in humans. Minor alleles of two common non-synonymous single-nucleotide polymorphisms (SNPs), rs6232 (T > C, N221D) and rs6235 (C > G, S690T), have been associated with increased risk of obesity in European populations. In this study, we compared the frequencies of the rs6232 and rs6234 (G > C, Q665E) SNPs in Aboriginal and Caucasian populations of Northern Ontario. The two SNPs were all relatively less frequent in Aboriginals: The minor allele frequency of the rs6232 SNP was 0.01 in Aboriginals and 0.08 in Caucasians (P < 4.10(-6)); for the rs6234 SNP, it was 0.20 and 0.32, respectively (P < 0.001). Resequencing revealed that the rs6234 SNP variation was tightly linked to that of the rs6235 SNP, as previously reported. Most interestingly, all carriers of the rs6232 SNP variation also carried the rs6234/rs6235 SNP clustered variations, but not the reverse, suggesting the former occurred later on an allele already carrying the latter. These data indicate that, in Northern Ontario Aboriginals, the triple-variant PCSK1 allele is relatively rare and might be of lesser significance for obesity risk in this population. PMID- 22307924 TI - Utility of routine follow-up head CT scanning after mild traumatic brain injury: a systematic review of the literature. AB - OBJECTIVE: To evaluate the efficacy of routine follow-up CT scans of the head after complicated mild traumatic brain injury (TBI). METHODS: 74 English language studies published from 1999 to February 2011 were reviewed. The papers were found by searching the PubMed database using a combination of keywords according to Cochrane guidelines. Excluding studies with missing or inappropriate data, 1630 patients in 19 studies met the inclusion criteria: complicated mild TBI, defined as a GCS score 13-15 with abnormal initial CT findings and the presence of follow up CT scans. For these studies, the progression and type of intracranial haemorrhage, time from trauma to first scan, time between first and second scans, whether second scans were obtained routinely or for neurological decline and the number of patients who had a neurosurgical intervention were recorded. RESULTS: Routine follow-up CT scans showed hemorrhagic progression in 324 patients (19.9%). Routine follow-up head CT scans did not predict the need for neurosurgical intervention (p=0.10) but a CT scan of the head performed for decline in status did (p=0.00046). For the 56 patients (3.4%) who declined neurologically, findings on the second CT scan were worse in 38 subjects (67%) and unchanged in the rest. Overall, 39 patients (2.4%) underwent neurosurgical intervention. CONCLUSION: Routine follow-up CT scans rarely alter treatment for patients with complicated mild TBI. Follow-up CT scans based on neurological decline alter treatment five times more often than routine follow-up CT scans. PMID- 22307925 TI - Intervention to reduce C-reactive protein determination requests for acute infections at an emergency department. AB - INTRODUCTION: C-reactive protein (CRP) levels rise during inflammatory processes and have been ordered for rheumatic disease follow-up since the 1950s. The number of tests ordered in the emergency setting has increased, but without evident improvement in medical care quality. OBJECTIVE: To determine the pattern of CRP determinations in the emergency department (ED) of a university hospital in Sao Paulo, Brazil, and to evaluate the effect of an intervention with staff and students about the best use of the test in the ED. METHODS: Data regarding CRP testing requests, related diagnoses and the number of monthly consultations in the hospital ED were analysed before and after the intervention. Because of an increase in CRP measurement requests from 2007 to 2009, the author started discussing the role of CRP determinations in the medical decision-making process in early 2010. Staff and faculty members openly discussed the pattern of requests in the hospital and related current medical literature. During 2010, the medical staff worked as multipliers to change the behaviour of new students and residents. The results of the first 4 months after the intervention were presented at another general meeting in July 2010. RESULTS: From 2007 to 2009, there were 11,786 CRP measurement requests with a clear exponential trend. After the intervention, during the calendar year 2010, there was a 48% reduction in adjusted annual CRP requests. Pneumonia, fever and urinary tract infections were the most common reasons for CRP requests. DISCUSSION: Inexpensive, well-directed, interactive educational interventions may affect professional behaviour and curb rates of laboratory tests. PMID- 22307926 TI - Emergency department management of undifferentiated abdominal pain with hyoscine butylbromide and paracetamol: a randomised control trial. AB - OBJECTIVE: To compare the effectiveness of paracetamol, hyoscine butylbromide and the combination of paracetamol plus hyoscine butylbromide (paracetamol + hyoscine butylbromide) in the management of patients with acute undifferentiated abdominal pain attending the emergency department (ED). SETTING: A large teaching hospital with an annual ED census of 120,000 adult patients. METHODS: A prospective, randomised placebo controlled trial of a convenience sample of patients attending the ED. The trial compared the analgesic effect of intravenous hyoscine butylbromide, oral paracetamol and the combination of both drugs using a Visual Analogue Scale pain scoring tool. Rescue analgesia was administered when pain was inadequately controlled by trial medication. RESULTS: 132 patients were recruited to the trial. At 30 min, all analgesic combinations produced significant similar levels of pain relief. At 60 min after administration of the trial medication, mean reductions in pain scores for patients receiving paracetamol only were significantly greater than those receiving paracetamol + hyoscine butylbromide (ANCOVA model, p=0.0180). No relationship was seen between treatment arm and the need for rescue analgesia (chi(2), p value=0.846). CONCLUSION: The trial data suggest that oral paracetamol is at least as effective as intravenous hyoscine butylbromide and a combination of both drugs in the management of acute undifferentiated abdominal pain presenting to the ED. Based on these results and factors such as cost and tolerability, we recommend single agent paracetamol as the agent of choice for the management of acute mild to moderate undifferentiated abdominal pain. TRIAL REGISTRATION NUMBER: MHRA Ref: 19717/0226/001-0001; European Clinical Trials Database. EUDRAct No: 2006-005395-40. PMID- 22307927 TI - How should individuals with a false-positive fecal occult blood test for colorectal cancer be managed? A decision analysis. AB - Several industrialized nations recommend fecal occult blood testing (FOBT) to screen for colorectal cancer (CRC), but corresponding screening guidelines do not specify how individuals with a prior false-positive FOBT result (fpFOBT) should be managed in terms of subsequent CRC screening. Accordingly, we conducted a decision analysis to compare different strategies for managing such individuals. We used a previously developed CRC microsimulation model, SimCRC, to calculate life-years and the lifetime number of colonoscopies (as a measure of required resources) for a cohort of 50-year-olds to whom FOBT-based CRC screening is offered annually from 50 to 75 years. We compared three management strategies for individuals with a prior fpFOBT: (i) resume screening in 10 years with 10-yearly colonoscopy (SwitchCol_long); (ii) resume screening in 1 year with annual FOBT (ContinueFOBT_Short) and (iii) resume screening in 10 years (i.e., the recommended interval following a negative colonoscopy) with annual FOBT (ContinueFOBT_long). We performed sensitivity analyses on various parameters and assumptions. When using different management strategies for individuals with a prior fpFOBT, the variation in the number of life-years gained relative to no screening was <2%, whereas the variation in the lifetime number of colonoscopies was 23% (percentages are calculated as the maximum difference across strategies divided by the lowest number across strategies). The ContinueFOBT_long strategy showed the lowest lifetime number of colonoscopies per life-year gained even when key assumptions were varied. In conclusion, the ContinueFOBT_long strategy was advantageous regarding both clinical benefit and required resources. Specifying an appropriate management strategy for individuals with a prior fpFOBT may substantially reduce required resources within a FOBT-based CRC screening program without limiting its effectiveness. PMID- 22307929 TI - Redox-active nickel in carbon nanotubes and its direct determination. AB - The presence of residual metal-catalyst impurities in carbon nanotubes is responsible for their toxicity. It is important to differentiate between the total amount of impurities and the redox-active (bioavailable) amount of such impurities because only the bioavailable impurities exhibit toxic effects. Herein, we report a simple and specific method for quantifying the amount of redox-active Ni present in various commercial samples of CNTs. It is based on the electrochemical oxidation of Ni(OH)(2) that is formed in alkaline solutions when Ni impurities are opened to the surrounding environment. Metallic Ni impurities play an extremely active role in toxicological assays as well as in undesired catalytic processes, and thus a method to rapidly quantify the amount of redox active Ni is of great importance. PMID- 22307928 TI - Interstrain differences in liver injury and one-carbon metabolism in alcohol-fed mice. AB - Alcoholic liver injury is a major public health issue worldwide. Even though the major mechanisms of this disease have been established over the past decades, little is known about genetic susceptibility factors that may predispose individuals who abuse alcoholic beverages to liver damage and subsequent pathological conditions. We hypothesized that a panel of genetically diverse mouse strains may be used to examine the role of endoplasmic reticulum (ER) stress and one-carbon metabolism in the mechanism of interindividual variability in alcoholic liver injury. We administered alcohol (up to 27 mg/kg/d) in a high fat diet using an intragastric intubation model for 28 days to male mice from 14 inbred strains (129S1/SvImJ, AKR/J, BALB/cJ, BALB/cByJ, BTBR T+tf/J, C3H/HeJ, C57BL/10J, DBA/2J, FVB/NJ, KK/HIJ, MOLF/EiJ, NZW/LacJ, PWD/PhJ, and WSB/EiJ). Profound interstrain differences (more than 3-fold) in alcohol-induced steatohepatitis were observed among the strains in spite of consistently high levels of urine alcohol that were monitored throughout the study. We found that ER stress genes were induced only in strains with the most liver injury. Liver glutathione and methyl donor levels were affected in all strains, albeit to a different degree. The most pronounced effects that were closely associated with the degree of liver injury were hyperhomocysteinemia and strain-dependent differences in expression patterns of one-carbon metabolism-related genes. CONCLUSION: Our data demonstrate that strain differences in alcohol-induced liver injury and steatosis are striking and independent of alcohol exposure and the most severely affected strains exhibit major differences in the expression of ER stress markers and genes of one-carbon metabolism. PMID- 22307930 TI - Lipoleiomyosarcoma of the larynx. AB - BACKGROUND: Lipoleiomyosarcoma is a rare tumor consisting of well-differentiated liposarcoma and leiomyosarcoma. The ear-nose-throat location of lipoleiomyosarcoma has not been previously described. METHODS AND RESULTS: A 37 year-old man with a dysphagia had a dyspnea after an endoscopy. A large tumor was exteriorized from the man's mouth. The lesion was pedicled to the epiglottis. A histologic examination determined that the tumor was a lipoleiomyosarcoma. MDM2 and CDK4 gene amplification were positive. Due to the risk of recurrence, a second intervention was performed to complete the excision. CONCLUSION: These tumors develop in cavities slowly and gradually. The treatment of this lesion is surgical with a sufficient resection margin. PMID- 22307931 TI - Appearing anxious leads to negative judgments by others. AB - OBJECTIVES: To investigate people's perceptions of anxiety symptoms and the disclosure of anxiety by others, and how one's own level of social anxiety affects these perceptions. DESIGN: Undergraduate students and community members high (n = 83) and low (n = 80) in social anxiety, as measured by the Social Interaction Anxiety Scale (SIAS; Mattick & Clark, 1998), were randomly assigned to watch 1 of 4 videos in which the target individual either appeared or did not appear anxious, and either disclosed or did not disclose her anxiety. Participants rated the target individual on various characteristics on which socially anxious individuals often fear being judged, and completed measures of their own level of social anxiety, perceived similarity to the target individual, and reasons for their ratings. RESULTS: Participants negatively evaluated others who looked anxious on qualities related to awkwardness, social skills, and weakness, and the disclosure of anxiety was associated with fewer negative judgments. Participants' own levels of social anxiety were not related to their judgments. CONCLUSIONS: This study provided evidence that the concerns held by socially anxious individuals that others will judge them negatively based on their signs of anxiety is accurate to a degree. These findings might inform the process of cognitive restructuring for social anxiety. PMID- 22307932 TI - Dipeptidyl peptidase IV (DPPIV/CD26)-based prodrugs of hydroxy-containing drugs. AB - We previously described a novel prodrug approach in which a di- or tetrapeptide moiety is linked to a wide variety of amine-containing drugs through an amide bond, which is specifically cleaved by dipeptidyl peptidase IV (DPPIV/CD26) activity. Herein we report the application of this prodrug approach to a variety of hydroxy-containing drugs (primary, secondary, tertiary, or aromatic hydroxy groups). We designed and studied tripartite prodrugs containing a dipeptide moiety (cleavable by DPPIV/CD26) and a valine as a hetero-bifunctional connector to link the dipeptide to the hydroxy group of the drug through a metabolically labile ester bond. The hydroxy-containing prodrugs showed various susceptibilities to hydrolysis by DPPIV/CD26 and serum, depending on the nature of the compound. Prodrugs of compounds containing a primary hydroxy group (as in didanosine) or a hydroxy moiety on an aromatic entity (as in acetaminophen) were most efficiently converted. In contrast, a tertiary hydroxy group was much less susceptible to conversion into its parent drug by DPPIV/CD26 or serum. A number of the prodrugs showed remarkable increases in water solubility relative to their parent drugs. PMID- 22307933 TI - Nonrigid motion correction in 3D using autofocusing with localized linear translations. AB - MR scans are sensitive to motion effects due to the scan duration. To properly suppress artifacts from nonrigid body motion, complex models with elements such as translation, rotation, shear, and scaling have been incorporated into the reconstruction pipeline. However, these techniques are computationally intensive and difficult to implement for online reconstruction. On a sufficiently small spatial scale, the different types of motion can be well approximated as simple linear translations. This formulation allows for a practical autofocusing algorithm that locally minimizes a given motion metric--more specifically, the proposed localized gradient-entropy metric. To reduce the vast search space for an optimal solution, possible motion paths are limited to the motion measured from multichannel navigator data. The novel navigation strategy is based on the so-called "Butterfly" navigators, which are modifications of the spin-warp sequence that provides intrinsic translational motion information with negligible overhead. With a 32-channel abdominal coil, sufficient number of motion measurements were found to approximate possible linear motion paths for every image voxel. The correction scheme was applied to free-breathing abdominal patient studies. In these scans, a reduction in artifacts from complex, nonrigid motion was observed. PMID- 22307934 TI - Steroidal glycosides from the rhizomes of Anemarrhena asphodeloides and their antiplatelet aggregation activity. AB - Five new steroidal glycosides, timosaponin J ( 1), timosaponin K ( 2), (25 S) karatavioside C ( 5), timosaponin L ( 6), and (25 S)-officinalisnin-I ( 8), together with eight known steroidal saponins, timosaponin E (1) ( 3), purpureagitosid ( 4), timosaponin BII ( 7), timosaponin B III ( 9), anemarrhenasaponin I ( 10), anemarrhenasaponin III ( 11), anemarrhenasaponin A (2) ( 12), and timosaponin A III ( 13), were isolated from the rhizomes of Anemarrhena asphodeloides. Their structures were elucidated on the basis of spectroscopic and chemical evidence. The aglycones of compounds 1 and 2 are new aglycones. Compounds 1- 13 were evaluated for their platelet aggregation activities, and compound 13 exhibited the strongest inhibitory effect on adenosine diphosphate (ADP)-induced platelet aggregation. PMID- 22307935 TI - Depsidones, aromatase inhibitors and radical scavenging agents from the marine derived fungus Aspergillus unguis CRI282-03. AB - Three new depsidones ( 1, 3, and 4), a new diaryl ether ( 5), and a new natural pyrone ( 9) (synthetically known), together with three known depsidones, nidulin ( 6), nornidulin ( 7), and 2-chlorounguinol ( 8), were isolated from the marine derived fungus ASPERGILLUS UNGUIS CRI282-03. Aspergillusidone C ( 4) showed the most potent aromatase inhibitory activity with the IC (50) value of 0.74 uM, while depsidones 1, 3, 6- 8 inhibited aromatase with IC (50) values of 1.2-11.2 uM. It was found that the structural feature of depsidones, not their corresponding diaryl ether derivatives (e.g. 5), was important for aromatase inhibitory activity. Aspergillusidones A ( 1) and B ( 3) showed radical scavenging activity in the XXO assay with IC (50) values of 16.0 and < 15.6 uM, respectively. Compounds 1 and 3- 7 were mostly inactive or showed only weak cytotoxic activity against HuCCA-1, HepG2, A549, and MOLT-3 cancer cell lines. PMID- 22307936 TI - Metabolism and pharmacokinetic study of ardipusilloside I in rats. AB - Ardipusilloside I, extracted from ARDISIA PUSILLA A.DC, effectively inhibits the progression of several cancers in animal models and is a potential anti-cancer drug candidate. However, the metabolism and pharmacokinetic characteristics of ardipusilloside I remain unknown. In this study, we developed a highly sensitive liquid chromatography-tandem MS method to determine the ardipusilloside I concentration in rat plasma using ginsenoside Re (whose structure is similar to ardipusilloside I) as the internal standard. After oral administration of ardipusilloside I, its four possible metabolites (M1, M2, M3, and M4, whose structures were determined by MS) were detected in the content from rat small intestine. In rat plasma, however, only M3 and M4 were detected after oral administration of ardipusilloside I. None of the metabolites were detected in plasma samples after intravenous administration of ardipusilloside I to rats. These results indicated that the metabolites, but not the drug itself, were absorbed into plasma after oral administration of ardipusilloside I to rats and that M3 and M4 may be responsible for the antitumor activity of orally administered ardipusilloside I in rat models of cancer. PMID- 22307937 TI - Ratanhiaphenol III from Ratanhiae radix is a PTP1B inhibitor. AB - The inhibition of protein tyrosine phosphatase 1B (PTP1B) is considered a valid strategy to combat insulin resistance and type II diabetes. We show here that a dichloromethane extract of Ratanhiae radix ( RR_EX) dose-dependently inhibits human recombinant PTP1B in vitro and enhances insulin-stimulated glucose uptake in murine myocytes. By determination of the PTP1B inhibiting potential of 11 recently isolated lignan derivatives from RR_EX, the observed activity of the extract could be partly assigned to ratanhiaphenol III. This compound inhibited PTP1B in vitro with an IC (50) of 20.2 uM and dose-dependently increased insulin receptor phosphorylation as well as insulin-stimulated glucose uptake in cultured myotubes. This is the first report to reveal an antidiabetic potential for a constituent of rhatany root, traditionally used against inflammatory disorders, by showing its capability of inhibiting PTP1B. PMID- 22307939 TI - Deficient inhibition of return in subclinical OCD only when attention is directed to the threatening aspects of a stimulus. AB - BACKGROUND: Inhibition of return (IOR) is thought to reflect inhibition of previously attended but irrelevant stimuli. Deficient IOR would increase the likelihood of revisiting previously searched locations or objects, thus leading to unproductive perseverations. METHOD: Therefore, using a novel IOR task, we investigated whether high scoring checkers attentional biases to threat would result in dysfunctional inhibitory functioning compared to low checkers. In two tasks, we compared 53 subclinical high and 49 low checkers regarding IOR effects for stimuli that were concordant with the concerns of high but not of low checkers (electrical kitchen appliances: e.g., toaster, kettle). The difference between the two tasks was the cueing procedure. In one task, an appliance was switched "ON" and "OFF" as an unpredictive cue, drawing attention to the functionality of the stimulus. RESULTS: In this task, IOR was specifically attenuated in high checkers. In the other task, however, the cue was more abstract in form of a yellow outline that appeared around one of two appliances. Although the appliance was either "ON" or "OFF," this did not seem to matter and high checkers revealed a typical IOR pattern similar to low checkers. CONCLUSIONS: We conclude that IOR mechanisms might not be generally deficient in high checkers; rather only when attention is drawn to the threatening aspects of ecologically valid stimuli, then disengagement of attention is deficient in high checkers. We make suggestions on how our task-specific findings may inform cognitive interventions that target attentional control in the treatment of checking/obsessive-compulsive disorder. PMID- 22307940 TI - Hypersensitivity reactions to dapsone: a systematic review. AB - Dapsone is widely used in the treatment of leprosy and several chronic inflammatory dermatological conditions. Hypersensitivity reactions to dapsone are potentially fatal adverse drug reactions with unknown prevalence and risk factors. We performed a systematic review covering all reported cases of hypersensitivity reactions, in order to systematically summarize the published evidence on prevalence, clinical course and fatality rate. Articles were identified through standardized search strategies. Included studies were reviewed for hypersensitivity characteristics and odds ratios were calculated in univariate and multivariate regression models to assess the risk factors for fatal outcome. A total of 114 articles (17 epidemiological studies, 97 case reports) totalling 336 patients with hypersensitivity reactions were included for analysis. From the epidemiological studies a total hypersensitivity reaction prevalence rate of 1.4% (95% confidence interval 1.2-1.7%) was determined. Mucosal involvement, hepatitis, higher age and disease occurrence in non-affluent countries were associated with higher risk of fatal outcome. Overall, the fatality rate was 9.9%. PMID- 22307941 TI - Cytokine production by infrapatellar fat pad can be stimulated by interleukin 1beta and inhibited by peroxisome proliferator activated receptor alpha agonist. AB - BACKGROUND: Infrapatellar fat pad (IPFP) might be involved in osteoarthritis (OA) by production of cytokines. It was hypothesised that production of cytokines is sensitive to environmental conditions. OBJECTIVES: To evaluate cytokine production by IPFP in response to interleukin (IL)1beta and investigate the ability to modulate this response with an agonist for peroxisome proliferator activated receptor alpha (PPARalpha), which is also activated by lipid-lowering drugs such as fibrates. METHODS: Cytokine secretion of IPFP was analysed in the medium of explant cultures of 29 osteoarthritic patients. IPFP (five donors) and synovium (six donors) were cultured with IL-1beta and PPARalpha agonist Wy14643. Gene expression of IL-1beta, monocyte chemoattractant protein (MCP1), (IL-6, tumour necrosis factor (TNF)alpha, leptin, vascular endothelial growth factor (VEGF), IL-10, prostaglandin-endoperoxide synthase (PTGS)2 and release of TNFalpha, MCP1 and prostaglandin E(2) were compared with unstimulated IPFP and synovium explants. RESULTS: IPFP released large amounts of inflammatory cytokines, adipokines and growth factors. IL-1beta increased gene expression of PTGS2, TNFalpha, IL-1beta, IL-6 and VEGF and increased TNFalpha release in IPFP. MCP1, leptin, IL-10 gene expression and MCP1, leptin and PGE(2) release did not increase significantly. Synovium responded to IL-1beta similarly to IPFP, except for VEGF gene expression. Wy14643 decreased gene expression of PTGS2, IL-1beta, TNFalpha, MCP1, VEGF and leptin in IPFP explants and IL-1beta, TNFalpha, IL-6, IL 10 and VEGF in synovium that responded to IL-1beta. CONCLUSION: IPFP is an active tissue within the joint. IPFP cytokine production is increased by IL-1beta and decreased by a PPARalpha agonist. The effects were similar to effects seen in synovium. Fibrates may represent a potential disease-modifying drug for OA by modulating inflammatory properties of IPFP and synovium. PMID- 22307942 TI - Safety and efficacy of ocrelizumab in combination with methotrexate in MTX-naive subjects with rheumatoid arthritis: the phase III FILM trial. AB - OBJECTIVE: To determine the efficacy and safety of ocrelizumab (OCR) with methotrexate (MTX) in MTX-naive rheumatoid arthritis (RA) patients. METHODS: In a randomised, double-blind, controlled trial, patients received placebo+MTX (MTX; n=210), OCR 200 mg*2+MTX (OCR 200; n=200) or OCR 500 mg*2+MTX (OCR 500; n=203). OCR/placebo (two intravenous infusions) was given on days 1 and 15, with fixed re treatment scheduled at weeks 24/26, 52/54 and 76/78. Due to early termination of OCR dosing, there was no formal primary end point analysis (change from baseline in modified total Sharp score (DeltamTSS) at week 104). Analyses are reported for week 52 outcomes. RESULTS: At week 52, treatment with OCR+MTX compared with MTX alone reduced progression of joint damage (mean (SD) change in DeltamTSS: OCR 200, 0.66 (4.51); OCR 500, 0.27 (2.91); MTX alone, 1.59 (4.82); p=0.001 and p=0.003, respectively vs MTX alone) and improved clinical signs and symptoms (American College of Rheumatology 20 response: OCR 200, 73.0%; OCR 500, 71.0%; MTX alone, 57.5%; p<0.005 for each OCR vs MTX alone). Serious infection rates per 100 patient-years were similar with OCR 200 and MTX alone (2.6 (95% CI 0.9 to 6.1) and 3.0 (1.1 to 6.5), respectively), but higher with OCR 500 (7.1 (3.9 to 11.9)). CONCLUSIONS: OCR 200 mg and 500 mg with MTX in MTX-naive patients with RA were effective in inhibiting joint damage progression and improving RA signs and symptoms. OCR 500 mg with MTX was associated with an increased rate of serious infections. PMID- 22307943 TI - Baseline characteristics and follow-up in patients with normal haemodynamics versus borderline mean pulmonary arterial pressure in systemic sclerosis: results from the PHAROS registry. AB - BACKGROUND: Patients with normal (mean pulmonary arterial pressure (mPAP) <=20 mm Hg) and borderline mean pulmonary pressures (21-24 mm Hg) are "at risk" of developing pulmonary hypertension (PH). The objectives of this analysis were to examine the baseline characteristics in systemic sclerosis (SSc) with normal and borderline mPAP and to explore long-term outcomes in SSc patients with borderline mPAP versus normal haemodynamics. METHODS: PHAROS is a multicentre prospective longitudinal cohort of patients with SSc "at risk" or recently diagnosed with resting PH on right heart catheterisation (RHC). Baseline clinical characteristics, pulmonary function tests, high-resolution CT, 2-dimensional echocardiogram and RHC results were analysed in normal and borderline mPAP groups. RESULTS: 206 patients underwent RHC (results showed 35 normal, 28 borderline mPAP, 143 resting PH). There were no differences in the baseline demographics. Patients in the borderline mPAP group were more likely to have restrictive lung disease (67% vs 30%), fibrosis on high-resolution CT and a higher estimated right ventricular systolic pressure on echocardiogram (46.3 vs 36.2 mm Hg; p<0.05) than patients with normal haemodynamics. RHC revealed higher pulmonary vascular resistance and more elevated mPAP on exercise (>=30; 88% vs 56%) in the borderline mPAP group (p<0.05 for both). Patients were followed for a mean of 25.7 months and 24 patients had a repeat RHC during this period. During follow-up, 55% of the borderline mPAP group and 32% of the normal group developed resting PH (p=NS). CONCLUSIONS: Patients with borderline mPAP have a greater prevalence of abnormal lung physiology, pulmonary fibrosis and the presence of exercise mPAP >=30 mm Hg. PMID- 22307944 TI - The association between two polymorphisms in the TS gene and risk of cancer: a systematic review and pooled analysis. AB - Thymidylate synthase (TS) is an important enzyme involved in folate metabolism and catalyzes methylation of deoxyuridine monophosphate to deoxythymidine monophosphate, which is essential for DNA replication. Thymidylate synthase enhancer region (TSER) and TS1494del6, two functionally important and ethnically diverse polymorphisms mapping to its gene region, are the most extensively studied. Considering the potential influence of altering TS activity, it is plausible that TS polymorphisms might play a role in the development of cancer. Although the effects of TS polymorphisms on susceptibility to human cancer have been investigated in many studies, the results remain conflicting rather than conclusive. To resolve these conflicts, we performed a quantitative synthesis of the evidence on the association between these two polymorphisms and cancer risk, including 63 studies (19,707 cases and 27,398 controls) for TSER polymorphism and 39 studies (13,489 cases and 16,297 controls) for TS1494del6 polymorphism. Our meta-analysis suggested that these two polymorphisms are not associated with cancer risk when all studies were pooled together. In the stratified analyses, we found that individuals with 2R/2R genotype had a significantly higher cancer risks among Asians (2R/2R vs. 3R/3R: odds ratio [OR] = 1.24, 95% confidence interval (95% CI) = 1.05-1.45; recessive model: OR = 1.23, 95% CI = 1.05-1.44). Further analyses revealed that 2R/2R genotype was significantly associated with an increased risk of gastroesophageal cancer among Asians, whereas it might provide protecting effects against colorectal cancer risk in a dominant genetic model for Caucasians. Additionally, TS1494del6 polymorphism may contribute to genetic susceptibility of breast cancer among Asians. PMID- 22307946 TI - A time-resolved in situ quick-XAS investigation of thermal activation of Fischer Tropsch silica-supported cobalt catalysts. PMID- 22307947 TI - Application of microfluidic systems in management of head and neck squamous cell carcinoma. AB - Microfluidics is an emerging multidisciplinary field that has the potential to provide solutions to many of the current challenges in managing head and neck squamous cell carcinoma (HNSCC). Treatment strategies for this disease are often complex and associated with significant morbidity and mortality; furthermore, prediction of response to treatment remains inaccurate. Microfluidic technology allows a small sample of tumor to be maintained alive ex vivo within a microenvironment that mimics the in vivo milieu; the response of this tumor biopsy to treatment regimens can subsequently be investigated. Microfluidics is the science and technology of systems that process or manipulate microliter to nanoliter volumes of fluids in purpose-built devices fabricated from glass or other biocompatible polymers. The technology also involves miniaturization and integration of various laboratory procedures into novel analysis devices. The purpose of this review is to provide an overview of microfluidic devices and discuss potential applications in HNSCC management. PMID- 22307948 TI - Mental health implications of human attachment to companion animals. AB - OBJECTIVES: Because of the contradictory nature of findings and methodological weaknesses identified within current human-companion animal bond research, there is a need to further explore the connection between human-animal bonds and mental health. DESIGN: The purpose of this survey questionnaire study was to explore the relationship of attachment to companion animal and human psychological distress after controlling for demographic variables, and to investigate whether the relationship between social supports and psychological distress would be moderated by attachment to a companion animal. RESULTS: Results highlight the psychological vulnerability of individuals reporting a strong bond with their companion animal. CONCLUSIONS: These findings are discussed in terms of their implications for mental health services designed to anticipate and address client related companion animal needs. PMID- 22307949 TI - Nuclear magnetic resonance spectroscopic analysis of ethyl ester yield in the transesterification of vegetable oil: an accurate method for a truly quantitative analysis. AB - Biodiesel has recently gained importance as an alternative to fossil diesel. However, the development of more efficient biodiesel formation processes still depends on the use of fast and accurate analytical techniques to evaluate the conversion degree of the transesterification reaction. Nuclear magnetic resonance (NMR) spectroscopy has been used for this purpose, but some experimental details still need to be addressed. Therefore, in this communication, the experimental conditions for a truly quantitative NMR analysis of biodiesel formation are presented. The longitudinal relaxation time (T(1) ), which is the determining factor for quantitative analysis, was measured using an inversion-recovery method, and a maximum value of 2.35 s was obtained for a biodiesel sample. A linear determination coefficient of r(2) = 0.99 was obtained when a time delay between pulses longer than 5T(1) =15 s was used, whereas strong deviations were observed when using shorter delays. PMID- 22307950 TI - Drosophila DREF acting via the JNK pathway is required for thorax development. AB - The Drosophila Jun N-terminal kinase (JNK) gene basket (bsk) promoter contains a DNA replication-related element (DRE)-like sequence, raising the possibility of regulation by the DNA replication-related element-binding factor (DREF). Chromatin immunoprecipitation assays with anti-DREF IgG showed the bsk gene promoter region to be effectively amplified. Luciferase transient expression assays revealed the DRE-like sequence to be important for bsk gene promoter activity, and knockdown of DREF decreased the bsk mRNA level and the bsk gene promoter activity. Furthermore, knockdown of DREF in the notum compartment of wing discs by pannier-GAL4 and UAS-DREFIR resulted in a split thorax phenotype. Monitoring of JNK activity in the wing disc by LacZ expression in a puckered (puc)-LacZ enhancer trap line revealed the reduction in DREF knockdown clones. These findings indicate that DREF is involved in regulation of Drosophila thorax development via actions on the JNK pathway. PMID- 22307951 TI - Polycyclic cage structures as lipophilic scaffolds for neuroactive drugs. AB - Polycyclic cage scaffolds have been successfully used in the development of numerous lead compounds demonstrating activity in the central nervous system (CNS). Several neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, schizophrenia, and stroke, as well as drug abuse, can be modulated with polycyclic cage derivatives. These cage moieties, including adamantane and pentacycloundecane derivatives, improve the pharmacokinetic and pharmacodynamic properties of conjugated parent drugs and serve as an important scaffold in the design of therapeutically active agents for the treatment of neurological disorders. In this Minireview, we focus on the recent developments in the field of polycyclic cage compounds, as well as the relationship between the lipophilic character of these cage-derived drugs and the ability of such compounds to target and reach the CNS and improve the pharmacodynamic properties of compounds conjugated to it. PMID- 22307952 TI - Highly active nanoreactors: nanomaterial encapsulation based on confined catalysis. AB - It happens inside: highly active nanoreactors are prepared by encapsulating dendritic Pt nanoparticles (NPs) grown on a polystyrene template inside hollow porous silica capsules. The catalytic activity of these Pt NPs is preserved after encapsulation and template removal. Different metals, such as Ni, can thus be reduced inside the capsules, thereby leading to the formation of composites with tunable magnetic properties. PMID- 22307953 TI - Hair depigmentation and vitiligo-like lesions in a leukaemic paediatric patient during chemotherapy with dasatinib. PMID- 22307954 TI - General joint frailty model for recurrent event data with a dependent terminal event: Application to follicular lymphoma data. AB - Many biomedical studies focus on delaying disease relapses and on prolonging survival. Usual methods only consider one event, often the first recurrence or death. However, ignoring the other recurrences may lead to biased results. The whole history of the disease should be considered for each patient. In addition, some diseases involve recurrences that can increase the risk of death. In this case, the death time may be dependent on the recurrent event history. We propose a joint frailty model to analyze recurrences and death simultaneously. Two gamma distributed frailties take into account both the inter-recurrences dependence and the dependence between the recurrences and the survival times. We estimate separate parameters for disease recurrent event times and survival times in the joint frailty model to distinguish treatment effects and prognostic factors on these two types of events. We show how maximum penalized likelihood estimation can be applied to semiparametric estimation of the continuous hazard functions in the proposed joint frailty model with right censoring. We also propose parametrical approach. We evaluate the model by simulation studies and illustrate through a study of patients with follicular lymphoma. PMID- 22307955 TI - A concise total synthesis of deoxyschizandrin and exploration of its antiproliferative effects and those of structurally related derivatives. AB - The natural product deoxyschizandrin has been shown to have a wide range of biological activities. In recent years the therapeutic potential of this compound against cancers has attracted significant interest. Herein we describe a concise de novo total synthesis of deoxyschizandrin based around a double organocuprate oxidation strategy. In addition, we present the results of biological studies exploring the ability of deoxyschizandrin and synthetic precursors lacking the medium ring biaryl unit to inhibit the proliferation of a human cancer cell line. These studies led to the identification of a structurally novel agent with in vitro anticancer activity. PMID- 22307956 TI - Significant overexpression of the Merkel cell polyomavirus (MCPyV) large T antigen in Merkel cell carcinoma. AB - BACKGROUND: The purpose of this study was to determine the expression pattern of the Merkel cell polyomavirus (MCPyV) large T-protein antigen in patients with Merkel cell carcinoma. METHODS: A tissue microarray (TMA) containing 30 specimens was constructed and stained for the MCPyV large T protein. Immunohistochemical expression was determined semiquantitively and was compared to patients' outcome. RESULTS: Nuclear expression of MCPyV large T protein was detected in 29 of 30 specimens (97%). In particular, 60% to 100%, 30% to 60%, and 10% to 30% of tumor cells were positive in 27 specimens (90%), 1 (3%), and 1 (3%), respectively. There was no difference in positivity between primary and metastatic lesions. Clinical data could not be correlated to MCPyV large T-protein expression. CONCLUSION: MCPyV large T protein was significantly overexpressed in 97% of all specimens. Although we could not demonstrate a predictive effect, MCPyV large T protein may represent a molecular marker with utility in pathological diagnosis as well as a potential new therapeutic target in patients with Merkel cell carcinoma. PMID- 22307957 TI - The prevalence of children affected by parental cancer and their use of specialized psychiatric services: the 1987 Finnish Birth Cohort study. AB - The studies reporting population-based estimates of the proportion of children with a parent suffering from cancer are very few. These children have been shown to suffer from psychological symptoms, but it is not known whether their use of psychiatric services is increased. Our study examined the prevalence of children affected by parental cancer at national level and whether these children use specialized psychiatric services more than their peers. The study is a retrospective population-based registry study. All 60,069 children born in Finland in 1987 were followed up with various health and social registers from 1987 to 2008. The associations of parental cancer treatments with children's psychiatric service use were analyzed with logistic regressions. During the 21 year follow-up 3,909 (6.6%) of the children had a parent suffering from cancer. The children of the cancer patients used more specialized psychiatric care than their peers and the service use depended on parent's gender, as well as cohort members' gender and the age at occurrence. The combination of parental cancer and psychiatric disorder, whether the ill parent or spouse, increased the children's psychiatric service use even more. Children affected by parental cancer comprise a substantial part of the population in society using increased level of psychiatric services. Parental cancer is clearly an illness which has to be taken into account in planning child- and parenting-focused prevention and promotion actions in adult health care. "Parent's cancer is like a tsunami which rolls over the whole family. If it struck a thousand families at the same time the whole healthcare system would be mobilized. But when it strikes one family at a time you are left alone with your children" (quote from a father during a family intervention). Weaver et al.1 have reported that 14% of all cancer survivors in the USA have minor dependent children, representing a population of about 1.58 million survivors and 2.85 million children. A significant part of working age population is thus struggling with concerns related to serious illness, parenting and the wellbeing of children. PMID- 22307958 TI - From parallel to intersecting narratives in cases of sexual assault. AB - Restorative justice alternatives to criminal justice are designed to balance the needs of victims, offenders, families, friends, and the community at large to achieve social justice, repair of victims, and deterrence of crime. In the model we evaluated from RESTORE (Responsibility and Equity for Sexual Transgressions Offering a Restorative Experience), each offender and victim received individual services and met in guided conferencing to mutually determine reparative actions for the offender. At the exit meeting, the offender, as the responsible person, read a written apology to the survivor/victim. In this article, we analyze the expression of empathy in the apology, in which the initial mitigation of responsibility in early documents was replaced by acknowledgment of harm to the survivor/victim and acceptance of responsibility for the assault. Those accused of felony rape and those targeting a visible person in cases of misdemeanor indecent exposure expressed greater regret and remorse than offenders of indecent exposure with an indeterminate victim. PMID- 22307959 TI - The factor structure and concurrent validity of the Korean version of the Metacognitions Questionnaire 30 (K-MCQ-30). AB - OBJECTIVES: We aimed to examine the factor structure of a Korean version of the Metacognitions Questionnaire 30 (K-MCQ-30) and to further evaluate its concurrent validity. METHOD: Confirmatory factor analyses were conducted on the data sets from two independent samples of Korean college students (n = 662; n = 664). Correlation and multiple regression analyses were conducted on the cross sectional data from another sample (n = 97). RESULTS: The 5-factor model of the K MCQ-30 showed a good fit to the first sample after minor modification. The revised 5-factor model was replicated with the second sample. Five factors of the K-MCQ-30 had positive correlations with measures of emotional disorder symptoms and predicted each of the symptoms in different ways. CONCLUSIONS: These results provide general support for the 5-factor structure of the K-MCQ-30 and its good concurrent validity in nonclinical samples. PMID- 22307960 TI - Design of a highly active Ir/Fe(OH)x catalyst: versatile application of Pt-group metals for the preferential oxidation of carbon monoxide. PMID- 22307961 TI - Unusual open chain quinolinyl peroxol and its alcohol counterpart obtained through a modified Skraup-Doebner-Von Miller quinoline synthesis: theoretical studies and complete (1) H- and (13) C-NMR assignments. AB - Because of their extreme instability, it is generally difficult to synthesize and fully characterize open chain peroxides, also known as peroxols. In our attempt to investigate the mechanism of the Skraup-Doebner-Von Miller quinoline synthesis, we were able to obtain an unusual open chain peroxy-quinoline, namely, 4-(8-ethoxy-2,3-dihydro-1H-cyclopenta[c]quinolin-4-yl)butane-1-peroxol (1), and its alcohol counterpart, namely 4-(8-ethoxy-2,3-dihydro-1H-cyclopenta[c]quinolin 4-yl)butan-1-ol (2) obtained as a side product during the same reaction. Although structurally similar, these two compounds appeared to display some very distinct physical and spectroscopic characteristics. This work reports detailed NMR studies and full (1) H and (13) C NMR assignments for these two compounds. These assignments are based upon the analysis of the NMR spectra of these compounds including (1) H, (13) C, COSY, gHSQC and gHMBC. The effect of the peroxide functional group on the chemical shift of neighboring carbons and protons was also investigated by comparing the NMR data of these two compounds. Furthermore, the effects of potential hydrogen bondings in 1, 2, and possible 1-1 dimer, 2-2 dimer and in prototypical model systems, as well as the stability of these compounds, were investigated computationally. The computed dissociation energies and NMR data support the interpretation of the experimental data. PMID- 22307962 TI - Modeling and optimization of membrane preparation conditions of the alginate based microcapsules with response surface methodology. AB - Microencapsulation has been a promising approach for drug delivery, cell implantation, cell-based gene therapy and large-scale cell culture. To make use of microcapsules more effectively, it is important to accurately construct the microcapsule membranes with desired properties including a certain thickness, strength, and so forth. To date single factor experiments have been widely used, however, they are time-consuming to obtain the desired membrane preparation conditions. Response surface methodology (RSM) is a mathematical and statistical technique for building empirical models that gained importance for optimizing reacting conditions. In this study, three signifficant effect factors that affect alginate-based microcapsule membrane properties, including membrane thickness, swelling degree, and mechanical stability, were determined with Plackett-Burman method, and then three empirical models were built to optimize the preparation conditions of the microcapsule membranes according to the responses of these three signifficant effect factors respectively with RSM. These models can be used to predict the characteristics of microcapsules under different membrane preparation conditions, which provide a guide for optimizing the microencapsulation technology. PMID- 22307963 TI - A two-step strategy for structure-activity relationship studies of N-methylated abeta42 C-terminal fragments as abeta42 toxicity inhibitors. AB - Neurotoxic Abeta42 oligomers are believed to be the main cause of Alzheimer's disease. Previously, we found that the C-terminal fragments (CTFs), Abeta(30-42) and Abeta(31-42) were the most potent inhibitors of Abeta42 oligomerization and toxicity in a series of Abeta(x-42) peptides (x=28-39). Therefore, we chose these peptides as leads for further development. These CTFs are short (12-13 amino acids) hydrophobic peptides with limited aqueous solubility. Our first attempt to attach hydrophilic groups to the N terminus resulted in toxic peptides. Therefore, we next incorporated N-methyl amino acids, which are known to increase the solubility of such peptides by disrupting the beta-sheet formation. Focusing on Abeta(31-42), we used a two-step N-methyl amino acid substitution strategy to study the structural factors controlling inhibition of Abeta42-induced toxicity. First, each residue was substituted by N-Me-alanine (N-Me-A). In the next step, in positions where substitution produced a significant effect, we restored the original side chain. This strategy allowed exploring the role of both side chain structure and N-Me substitution in inhibitory activity. We found that the introduction of an N-Me amino acid was an effective way to increase both the aqueous solubility and the inhibitory activity of Abeta(31-42). In particular, N Me amino acid substitution at position 9 or 11 increased the inhibitory activity relative to the parent peptide. The data suggest that inhibition of Abeta42 toxicity by short peptides is highly structure-specific, providing a basis for the design of new peptidomimetic inhibitors with improved activity, physicochemical properties, and metabolic stability. PMID- 22307964 TI - Classification accuracy and cut point selection. AB - In biomedical research and practice, quantitative tests or biomarkers are often used for diagnostic or screening purposes, with a cut point established on the quantitative measurement to aid binary classification. This paper introduces an alternative to the traditional methods based on the Youden index and the closest to-(0, 1) criterion for threshold selection. A concordance probability evaluating the classification accuracy of a dichotomized measure is defined as an objective function of the possible cut point. A nonparametric approach is used to search for the optimal cut point maximizing the objective function. The procedure is shown to perform well in a simulation study. Using data from a real-world study of arsenic-induced skin lesions, we apply the method to a measure of blood arsenic levels, selecting a cut point to be used as a warning threshold. PMID- 22307965 TI - A lipid droplet protein of Nannochloropsis with functions partially analogous to plant oleosins. AB - As our understanding of the dynamics of lipid droplets (LDs) in animal, plant, and fungal cells is rapidly evolving, still little is known about the formation and turnover of these organelles in microalgae. Yet with the growing importance of algal feedstock for the production of biofuels and high-value lipids, there is a need to understand the mechanisms of LD dynamics in microalgae. Thus, we investigated the proteins associated with LDs of the emerging heterokont model alga Nannochloropsis sp. and discovered an abundant hydrophobic lipid droplet surface protein (LDSP) with unique primary sequence but structural similarities to other LD proteins. LDSP abundance in Nannochloropsis cells closely tracked the amount of triacylglycerols during conditions of oil accumulation and degradation. Functional characterization of LDSP in an Arabidopsis (Arabidopsis thaliana) OLEOSIN1-deficient mutant allowed a separation of its physical and structural properties in its interaction with LDs from its physiological or biochemical activities. Although LDSP presence in Arabidopsis predictably affected LD size, it could not reverse the physiological impact of OLEOSIN deficiency on triacylglycerol hydrolysis during germination. PMID- 22307967 TI - Toxic epidermal necrolysis arising as a sequela of drug-induced hypersensitivity syndrome. PMID- 22307966 TI - Exploring tomato gene functions based on coexpression modules using graph clustering and differential coexpression approaches. AB - Gene-to-gene coexpression analysis provides fundamental information and is a promising approach for predicting unknown gene functions in plants. We investigated various associations in the gene expression of tomato (Solanum lycopersicum) to predict unknown gene functions in an unbiased manner. We obtained more than 300 microarrays from publicly available databases and our own hybridizations, and here, we present tomato coexpression networks and coexpression modules. The topological characteristics of the networks were highly heterogenous. We extracted 465 total coexpression modules from the data set by graph clustering, which allows users to divide a graph effectively into a set of clusters. Of these, 88% were assigned systematically by Gene Ontology terms. Our approaches revealed functional modules in the tomato transcriptome data; the predominant functions of coexpression modules were biologically relevant. We also investigated differential coexpression among data sets consisting of leaf, fruit, and root samples to gain further insights into the tomato transcriptome. We now demonstrate that (1) duplicated genes, as well as metabolic genes, exhibit a small but significant number of differential coexpressions, and (2) a reversal of gene coexpression occurred in two metabolic pathways involved in lycopene and flavonoid biosynthesis. Independent experimental verification of the findings for six selected genes was done using quantitative real-time polymerase chain reaction. Our findings suggest that differential coexpression may assist in the investigation of key regulatory steps in metabolic pathways. The approaches and results reported here will be useful to prioritize candidate genes for further functional genomics studies of tomato metabolism. PMID- 22307968 TI - Ethmoid sinus osteoma: diagnosis and management. AB - BACKGROUND: Ethmoid sinus osteomas are uncommon, benign, osteogenic tumors. The purpose of this retrospective study was to describe their usual clinical presentation and to discuss their surgical management. METHODS: The medical records of 25 patients treated for ethmoid osteoma between March 2001 and December 2010 were retrospectively reviewed. RESULTS: The average tumor size was 18.5 +/- 14 mm. Only 3 patients were asymptomatic, 14 had a history of frontal sinusitis (complicated with orbital cellulitis in 4 cases), and 4 patients presented with diplopia. An endoscopic approach was performed in 19 cases, a coronal approach in 4 cases, and a combined approach (endoscopic + coronal) in 2 cases. No recurrence was reported. CONCLUSION: Ethmoid sinus osteoma can be asymptomatic and detected incidentally on CT scans, but often causes frontal sinusitis and orbital complications. The endoscopic approach offers the possibility of safe removal with cosmetic advantages compared to coronal approach. PMID- 22307969 TI - Morphing the torsional potential energy function from local to global symmetry through a pi link: the rotational spectrum of alpha,alpha,alpha-trifluoro-p tolualdehyde. PMID- 22307970 TI - Public speaking in social phobia: a pilot study of self-ratings and observers' ratings of social skills. AB - OBJECTIVES: The aim of this pilot study was to investigate whether patients with social anxiety disorder (SAD) differ from controls in the quality of skill related behaviors displayed during a speech and in overall behavioral adequacy as perceived by observers and by the patients themselves. DESIGN: A total of 18 SAD patients and 18 controls were screened by a diagnostic interview and took part in a 3-minute speech of their own choosing. For each videotaped speech, observers rated the adequacy of the skill-related behaviors and overall performance adequacy. After the experiment, participants were asked to rate their own overall performance adequacy. RESULTS: The results showed that SAD patients exhibited significantly worse voice intonation and fluency of the speech, however no differences were found in global self-ratings. Moreover, the performance evaluations of the SAD group were consistent with the observers, while the controls evaluated their performance lower than the observers. CONCLUSIONS: The results are inconsistent with the cognitive model, because patients with SAD did not underestimate their performance. Compared with spontaneous interactions, the clear rules established for such social situations as speeches may result in less cognitive distortion for SAD patients. PMID- 22307971 TI - Intervention of human breast cell carcinogenesis chronically induced by 2-amino-1 methyl-6-phenylimidazo[4,5-b]pyridine. AB - More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens, such as those in the diet, through a multistep disease process progressing from non-cancerous to premalignant and malignant stages. The chemical carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5 b]pyridine (PhIP) is one of the most abundant heterocyclic amines found in high temperature cooked meats and is recognized as a mammary carcinogen. However, the PhIP's mechanism of action in breast cell carcinogenesis is not clear. Here, we demonstrated, for the first time, that cumulative exposures to PhIP at physiologically achievable, pico to nanomolar concentrations effectively induced progressive carcinogenesis of human breast epithelial MCF10A cells from a non cancerous stage to premalignant and malignant stages in a dose- and exposure dependent manner. Progressive carcinogenesis was measured by increasingly- acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, acinar-conformational disruption, proliferation, migration, invasion, tumorigenicity with metastasis and increased stem-like cell populations. These biological changes were accompanied by biochemical and molecular changes, including upregulated H-Ras gene expression, extracellular signal-regulated kinase (ERK) pathway activation, Nox-1 expression, reactive oxygen species (ROS) elevation, increased HIF-1alpha, Sp1, tumor necrosis factor alpha, matrix metalloproteinase (MMP)-2, MMP-9, aldehyde dehydrogenase activity and reduced E-cadherin. The Ras-ERK-Nox-ROS pathway played an important role in not only initiation but also maintenance of cellular carcinogenesis induced by PhIP. Using biological, biochemical and molecular changes as targeted endpoints, we identified that the green tea catechin components epicatechin-3-gallate and epigallocatechin-3-gallate, at non-cytotoxic doses, were capable of suppressing PhIP-induced cellular carcinogenesis and tumorigenicity. PMID- 22307972 TI - Promoter methylation of aminopeptidase N/CD13 in malignant melanoma. AB - Aminopeptidase N (APN)/CD13 as ubiquitously expressed membrane peptidase exerts important functions in diverse cellular processes, such as proliferation, migration and differentiation. Previously, a role of APN in the invasiveness of melanoma cells has been demonstrated, but the underlying molecular mechanisms controlling APN expression are not understood. The present study demonstrates that lack of APN expression in primary and established melanoma cells was directly associated with a high-grade DNA methylation status of the myeloid APN promoter. Demethylation by 5-aza-2'-desoxycytidine not only induced constitutive and cytokine-regulated APN protein expression but also resulted in an increased APN-dependent migration of melanoma cells. Furthermore, its heterogeneous expression was inversely correlated to the expression of melanocytic marker proteins in established as well as in short-term cultured human melanoma cells. Staining of tissue microarrays generated from a large series of melanoma samples and control tissues demonstrated a higher APN expression in primary melanoma lesions when compared with nevi and metastases, which was neither associated with clinico-pathological parameters nor with the patients' outcome. Thus, the heterogeneous APN expression pattern in melanoma cells is epigenetically controlled and directly associated with an altered migration capacity but not of clinical significance in our study group. PMID- 22307973 TI - More than just talk. PMID- 22307974 TI - Evidence of an evolutionarily conserved LMBR1 domain-containing protein that associates with endocytic cups and plays a role in cell migration in dictyostelium discoideum. AB - The ampA gene plays a role in Dictyostelium discoideum cell migration. Loss of ampA function results in reduced ability of growing cells to migrate to folic acid and causes small plaques on bacterial lawns, while overexpression of AmpA results in a rapid-migration phenotype and correspondingly larger plaques than seen with wild-type cells. To help understand how the ampA gene functions, second site suppressors were created by restriction enzyme-mediated integration (REMI) mutagenesis. These mutants were selected for their ability to reduce the large plaque size of the AmpA overexpresser strain. The lmbd2B gene was identified as a suppressor of an AmpA-overexpressing strain. The lmbd2B gene product belongs to the evolutionarily conserved LMBR1 protein family, some of whose known members are endocytic receptors associated with human diseases, such as anemia. In order to understand lmbd2B function, mRFP fusion proteins were created and lmbd2B knockout cell lines were established. Our findings indicate that the LMBD2B protein is found associated with endocytic cups. It colocalizes with proteins that play key roles in endocytic events and is localized to ruffles on the dorsal surfaces of growing cells. Vegetative lmbd2B-null cells display defects in cell migration. These cells have difficulty sensing the chemoattractant folic acid, as indicated by a decrease in their chemotactic index. lmbd2B-null cells also appear to have difficulty establishing a front/back orientation to facilitate migration. A role for lmbd2B in development is also suggested. Our research gives insight into the function of a previously uncharacterized branch of the LMBR1 family of proteins. We provide evidence of an LMBR1 family plasma membrane protein that associates with endocytic cups and plays a role in chemotaxis. PMID- 22307975 TI - Bul proteins, a nonredundant, antagonistic family of ubiquitin ligase regulatory proteins. AB - Like other Nedd4 ligases, Saccharomyces cerevisiae E3 Rsp5p utilizes adaptor proteins to interact with some substrates. Previous studies have indentified Bul1p and Bul2p as adaptor proteins that facilitate the ligase-substrate interaction. Here, we show the identification of a third member of the Bul family, Bul3p, the product of two adjacent open reading frames separated by a stop codon that undergoes readthrough translation. Combinatorial analysis of BUL gene deletions reveals that they regulate some, but not all, of the cellular pathways known to involve Rsp5p. Surprisingly, we find that Bul proteins can act antagonistically to regulate the same ubiquitin-dependent process, and the nature of this antagonistic activity varies between different substrates. We further show, using in vitro ubiquitination assays, that the Bul proteins have different specificities for WW domains and that the two forms of Bul3p interact differently with Rsp5p, potentially leading to alternate functional outcomes. These data introduce a new level of complexity into the regulatory interactions that take place between Rsp5p and its adaptors and substrates and suggest a more critical role for the Bul family of proteins in controlling adaptor-mediated ubiquitination. PMID- 22307976 TI - Delta-aminolevulinate-induced host-parasite porphyric disparity for selective photolysis of transgenic Leishmania in the phagolysosomes of mononuclear phagocytes: a potential novel platform for vaccine delivery. AB - Leishmania double transfectants (DTs) expressing the 2nd and 3rd enzymes in the heme biosynthetic pathway were previously reported to show neogenesis of uroporphyrin I (URO) when induced with delta-aminolevulinate (ALA), the product of the 1st enzyme in the pathway. The ensuing accumulation of URO in DT promastigotes rendered them light excitable to produce reactive oxygen species (ROS), resulting in their cytolysis. Evidence is presented showing that the DTs retained wild-type infectivity to their host cells and that the intraphagolysosomal/parasitophorous vacuolar (PV) DTs remained ALA inducible for uroporphyrinogenesis/photolysis. Exposure of DT-infected cells to ALA was noted by fluorescence microscopy to result in host-parasite differential porphyrinogenesis: porphyrin fluorescence emerged first in the host cells and then in the intra-PV amastigotes. DT-infected and control cells differed qualitatively and quantitatively in their porphyrin species, consistent with the expected multi- and monoporphyrinogenic specificities of the host cells and the DTs, respectively. After ALA removal, the neogenic porphyrins were rapidly lost from the host cells but persisted as URO in the intra-PV DTs. These DTs were thus extremely light sensitive and were lysed selectively by illumination under nonstringent conditions in the relatively ROS-resistant phagolysosomes. Photolysis of the intra-PV DTs returned the distribution of major histocompatibility complex (MHC) class II molecules and the global gene expression profiles of host cells to their preinfection patterns and, when transfected with ovalbumin, released this antigen for copresentation with MHC class I molecules. These Leishmania mutants thus have considerable potential as a novel model of a universal vaccine carrier for photodynamic immunotherapy/immunoprophylaxis. PMID- 22307977 TI - Hyperstoichiometric interaction between silver and mercury at the nanoscale. AB - Breaking through the stoichiometry barrier: as the diameter of silver particles is decreased below a critical size of 32 nm, the molar ratio of aqueous Hg(II) to Ag(0) drastically increases beyond the conventional Hg/Ag ratio of 0.5:1, leading to hyperstoichiometry with a maximum ratio of 1.125:1. Therein, around 99% of the initial silver is retained to rapidly form a solid amalgam with reduced mercury. PMID- 22307978 TI - Multipotent progenitors resident in the skeletal muscle interstitium exhibit robust BMP-dependent osteogenic activity and mediate heterotopic ossification. AB - Heterotopic ossification is a debilitating condition that can result from traumatic injury, surgery, or genetic disease. We investigated the cellular origins of heterotopic skeletogenesis in the mouse using lineage tracing and bioassays of heterotopic ossification based on intramuscular transplantation. We identified, characterized, and purified a tissue-resident stem/progenitor cell population that exhibits robust osteogenic potential and represents a major cell of-origin for heterotopic ossification. These progenitors reside in the interstitium of skeletal muscle and other tissues, and are distinct from the endothelium, which does not exhibit osteogenic activity in response to bone morphogenetic protein 2 (BMP2) stimulation. Intramuscular transplantation, together with clonal analysis in culture, revealed that these progenitors are multipotent, exhibiting the capacity for both BMP-dependent skeletogenic differentiation and spontaneous adipogenic differentiation. Identifying the cells of-origin responsible for heterotopic ossification provides a potential therapeutic target to treat, mitigate, or prevent this disabling condition. PMID- 22307979 TI - Sulfonimidamides as sulfonamides bioisosteres: rational evaluation through synthetic, in vitro, and in vivo studies with gamma-secretase inhibitors. PMID- 22307980 TI - Herpes zoster in patients with drug-induced hypersensitivity syndrome/DRESS. PMID- 22307981 TI - Simple synthesis of platinum dendritic aggregates supported on conductive tungsten oxide nanowires as high-performance methanol oxidation electrocatalysts. PMID- 22307982 TI - Naturalistic changes in subjective distress outside of therapy. AB - OBJECTIVES: To establish the effectiveness or efficacy of psychological interventions, it is important to understand the nature of changes that occur in the absence of therapy. DESIGN: In this study, clinically distressed college students from 2 universities (n = 228) completed the Outcome Questionnaire (OQ) 45.2 on a weekly basis throughout a single semester. RESULTS: Although 56.6% of the sample made no change or deteriorated, 43.4% made a reliable improvement. Change status was predicted by previous therapy experience and length of study participation. Multilevel growth modeling also indicated that participants' OQ 45.2 scores decreased over time (following a cubic trend) and the amount of decrease was associated with Time 1 OQ-45.2 scores. CONCLUSIONS: Limitations of the study and further implications for treatment outcome research are discussed. PMID- 22307983 TI - Pseudo-Gaucher cells in disseminated mycobacterial infection. PMID- 22307984 TI - Electrodeposition of hydroxyapatite coating on Mg-4.0Zn-1.0Ca-0.6Zr alloy and in vitro evaluation of degradation, hemolysis, and cytotoxicity. AB - A novel biodegradable Mg-4.0Zn-1.0Ca-0.6Zr (wt %) alloy was successfully produced using a series of metallurgical processes; including melting, casting, rolling, and heat treatment. The hardness and ultimate tensile strength of the alloy sheets increased to 71.2HV and 320 MPa after rolling and then aging for 12 h at 175 degrees C. These mechanical properties were sufficient for load-bearing orthopedic implants. A hydroxyapatite (HA) coating was deposited on the Mg-4.0Zn 1.0Ca-0.6Zr (wt %) alloy using a novel coating process combining alkali heat pretreatment, electrodeposition, and alkali heat posttreatment. The microstructure, composition, and phases of the Mg-4.0Zn-1.0Ca-0.6Zr (wt %) alloy and HA coating were characterized using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD). The degradation, hemolysis, and cytocompatibility of the HA-coated and uncoated Mg 4.0Zn-1.0Ca-0.6Zr (wt %) alloy were studied in vitro. The corrosion potential (E(corr)) of Mg-4.0Zn-1.0Ca-0.6Zr alloy (-1.72 V) was higher than Mg (-1.95 V), Mg-0.6Ca alloy (-1.91 V) and Mg-1.0Ca alloy (-1.97 V), indicating the Mg-Zn-Ca-Zr alloy would be more corrosion resistant. The initial corrosion potential of the HA-coated Mg alloy sample (-1.51 V) was higher than the uncoated sample (-1.72 V). The hemolysis rates of the HA-coated and uncoated Mg-4.0Zn-1.0Ca-0.6Zr (wt %) alloy samples were both <5%, which met the requirements for implant materials. The HA-coated and uncoated Mg-4.0Zn-1.0Ca-0.6Zr (wt %) alloy samples demonstrated the same cytotoxicity score as the negative control. The HA-coated samples showed a slightly greater relative growth rate (RGR%) of fibroblasts than the uncoated samples. Both the HA-coated and uncoated Mg-4.0Zn-1.0Ca-0.6Zr (wt %) alloy provided evidence of acceptable cytocompatibility for medical applications. PMID- 22307985 TI - Voice and swallowing after partial laryngectomy: factors influencing outcome. AB - BACKGROUND: The purpose of this study was to assess the factors influencing swallowing and phonatory results after partial laryngectomy. METHODS: We carried out a medical chart review of patients who underwent partial laryngectomies between June 2003 and November 2010, focusing on functional outcomes. RESULTS: Thirty-two patients were enrolled. No statistically significant difference was found in the comparison of phonatory outcomes of patients with preservation of both arytenoids; the results of the Yanagihara classification were significantly different (p = .015) in patients with an atypical neoglottis; radiotherapy statistically significantly influenced only the mean fundamental frequency (p = .035). The type of partial laryngectomy does not seem to affect the deglutition results; radiotherapy statistically significantly affected the dysphagia score (DS; p = .03), penetration aspiration (p = .02), and MD Anderson Dysphagia Inventory (MDADI; p = .02). CONCLUSION: Horizontal supraglottic laryngectomy and supracricoid partial laryngectomy give the same swallowing results. The presence of both arytenoids does not influence the final outcome compared to patients in whom only 1 arytenoid is preserved. Postoperative radiotherapy only influences the swallowing function. PMID- 22307986 TI - High-contrast reversible fluorescence photoswitching of dye-crosslinked dendritic nanoclusters in living vertebrates. PMID- 22307987 TI - A disjointed effort: paediatric musculoskeletal examination. AB - BACKGROUND: Musculoskeletal (MSK) symptoms are a frequent cause of emergency department attendance for children, and while most often indicative of benign or self-limiting disease, such symptoms can occasionally be the first presentation of serious illness such as leukaemia or juvenile idiopathic arthritis. MSK examination, however, is often not included as part of the routine paediatric examination. The authors aimed to evaluate how often and how thoroughly MSK examination was performed during admissions to the paediatric ward and to compare it with the examination of other symptoms in relation to the presenting complaint and eventual diagnosis. RESULTS: Medical records for 100 consecutive patients were reviewed. A poster campaign to increase awareness was then commenced along with oral and written presentations to staff regarding MSK examination. A further 100 consecutive patients were then reviewed. Only 9% of children in the initial group had routine MSK examination, rising to 32% in the second group. Where performed, MSK examination was often incomplete. Frequent errors included only examining the reported site of injury and only examining a single limb or single joint when limpness/stiffness was the presenting complaint. Non-limb joints were very rarely examined. CONCLUSIONS: MSK examination is not performed routinely during paediatric admissions in contrast to the examination of other symptoms regardless of the presenting complaint. This may need to be addressed by local audit and increased undergraduate teaching. PMID- 22307988 TI - The skeletal consequences of meningococcal septicaemia. AB - Meningococcal disease remains a leading cause of childhood mortality in the UK. Advances in resuscitation have resulted in survival of severely affected individuals and the long-term skeletal consequences are being increasingly recognised. The immediate management of the ischaemic limb in the context of a critically ill and haemodynamically unstable child is described and the indications for fasciotomy and amputation are considered. Long-term disability occurs as a consequence of limb malalignment and is often accompanied by significant injury to the soft tissue envelope. The function of surviving limbs can be enhanced using contemporary surgical techniques that involve realignment and lengthening. Amputees present specific difficulties due to the effect of remaining longitudinal growth on the function of the residual limb, and require surgical treatment that often continues throughout childhood. This overview considers the surgical algorithms that have evolved to treat these patients. PMID- 22307989 TI - Bullous Henoch Schonlein purpura. PMID- 22307991 TI - Analysis of the Constituents in Rat Serum after Oral Administration of Fufang Zhenzhu Tiaozhi Capsule by UPLC-Q-TOF-MS/MS. AB - A rapid and sensitive UPLC/Q-TOF-MS method has been established for analysis of the constituents in rat serum after oral administration of Fufang Zhenzhu Tiaozhi (FTZ) capsule, an effective compound prescription for treating hyperlipidemia in the clinic. The UPLC/MS information of samples was obtained first in FTZ preparation and FTZ-treated rat serum. Mass spectra were acquired in both negative and positive ion modes. Thirty-six constituents in rat serum after oral administration of FTZ were detected, including the alkaloids, ginsenosides, pentacyclic triterpenes, and their metabolites. These chemicals were identified based on the retention time and mass spectrometry data with those of authentic standards or comparison of the literatures reports. Twenty-seven prototype components originated from FTZ and nine were the metabolites of the FTZ constituents. These results shed light on the potential active constituents of the complex traditional Chinese medicinal formulas. PMID- 22307992 TI - Discovery of [(2R,5R)-5-{[(5-fluoropyridin-2-yl)oxy]methyl}-2-methylpiperidin-1 yl][5-methyl-2-(pyrimidin-2-yl)phenyl]methanone (MK-6096): a dual orexin receptor antagonist with potent sleep-promoting properties. AB - Insomnia is a common disorder that can be comorbid with other physical and psychological illnesses. Traditional management of insomnia relies on general central nervous system (CNS) suppression using GABA modulators. Many of these agents fail to meet patient needs with respect to sleep onset, maintenance, and next-day residual effects and have issues related to tolerance, memory disturbances, and balance. Orexin neuropeptides are central regulators of wakefulness, and orexin antagonism has been identified as a novel mechanism for treating insomnia with clinical proof of concept. Herein we describe the discovery of a series of alpha-methylpiperidine carboxamide dual orexin 1 and orexin 2 receptor (OX(1) R/OX(2) R) antagonists (DORAs). The design of these molecules was inspired by earlier work from this laboratory in understanding preferred conformational properties for potent orexin receptor binding. Minimization of 1,3-allylic strain interactions was used as a design principle to synthesize 2,5-disubstituted piperidine carboxamides with axially oriented substituents including DORA 28. DORA 28 (MK-6096) has exceptional in vivo activity in preclinical sleep models, and has advanced into phase II clinical trials for the treatment of insomnia. PMID- 22307993 TI - LIMITED GEOGRAPHIC VARIATION IN THE VOCALIZATIONS OF THE ENDANGERED THICK-BILLED PARROT: IMPLICATIONS FOR CONSERVATION STRATEGIES. AB - The populations of many species are declining worldwide, and conservation efforts struggle to keep pace with extinction rates. Conservation biologists commonly employ strategies such as translocation and reintroduction, which move individuals of endangered species from one part of their range to another. Because individuals from endangered populations are nonexpendable, identifying any potential barriers to the establishment of viable populations prior to release of individuals should be a priority. This study evaluates the potential for learned communication signals to constrain conservation strategies such as reintroduction in an endangered species, the Thick-billed Parrot (Rhynchopsitta pachyrhyncha). We conducted vocal surveys at three geographically distinct breeding populations in the Sierra Madre Occidental of Chihuahua, Mexico. Acoustic analyses utilizing both spectrogram cross-correlations and parameter measurements from spectrograms revealed no significant differences among the three sites in two common call types. Calls did vary among individuals within a site. The apparent lack of significant geographic variation across sampled sites suggests that differences in learned communication signals are unlikely to pose a barrier to the integration of translocated individuals from different populations into newly established populations. PMID- 22307994 TI - Low back pain and neck pain as predictors of sickness absence among municipal employees. AB - OBJECTIVE: To study whether having ever had local low back pain (LBP), sciatica, neck pain (NP), or some combination of LBP and NP, predicts sickness absence among municipal employees. METHODS: The study sample (n=6911, 80% women, response rate 67%) included employees of the City of Helsinki who reached the age of 40, 45, 50, 55, or 60 years between 2000-02. Survey data on pain, working conditions, and health behaviours were linked to register data on sickness absence for three subsequent years. Sickness absence was categorised as self-certified (lasting for 1-3 days) and medically certified (lasting for 4 days or more) and the number of spells during the follow up was analysed using Poisson regression analysis. RESULTS: In women, medically certified sickness absence was predicted by sciatica (rate ratio, RR, 1.3, 95% CI 1.1-1.6), NP (RR 1.3, 95% CI 1.2-1.5) and the combination of sciatica and NP (RR 1.8, 95% CI 1.6-2.1), allowing for working conditions, body mass index, and smoking. In men, the corresponding RRs were 1.5 (95% CI 1.0-2.1), 1.7 (95% CI 1.2-2.4), and 2.2 (95% CI 1.6-2.9). Local LBP did not predict medically certified sickness absence. Self-certified sickness absence was modestly predicted by all pain categories in women (RRs between 1.2 and 1.5) and by NP alone and with local LBP or sciatica in men (RRs between 1.4 and 1.6). CONCLUSIONS: Medically certified sickness absence was predicted by sciatica and NP, but not by local LBP. The association was accentuated in those with both sciatica and NP. Pain combinations may have a stronger effect on work ability than pain in one location. PMID- 22307995 TI - Excluded from social security: rejections of disability pension applications in Norway 1998-2004. AB - AIMS: Admission to disability pension (DP) in Norway, like most other countries, requires a medical condition as the main cause of income reduction. Still, a widespread assumption is that much of the recruitment to the programme is rather due to non-medical, mainly labour market factors. In this article, we study the grey zones between acceptance and rejection of DP applications, in light of the concept of marginalisation. METHODS: From the total Norwegian population, aged 18 66 in 1998, we included all first-time applications for DP between 1998 and 2004. Logistic regressions of both application and application outcome were then performed, controlling for a range of socioeconomic variables and medical diagnosis. RESULTS: Medical diagnosis had the strongest impact on application outcome, together with the applicant's age. High rejection risk was found among applicants with complex musculoskeletal diagnoses, and also for complex psychiatric diagnoses as compared to well-defined ones. Persons having previously received social assistance more often applied for a DP and more often were rejected. The same is true, though on a lesser scale, for people with a weak affiliation to the labour market. CONCLUSIONS: The DP programme in Norway is to a large degree medically oriented, not only judicially but also in practice. Nevertheless, non-medical factors have a bearing on both application rates and application outcome. The control system seems to work in a way that excludes the most marginalised applicants, thus possibly contributing to further marginalisation of already disadvantaged groups. PMID- 22307996 TI - Risk factors among men who have repeated experience of being the partner of a woman who requests an induced abortion. AB - BACKGROUND: Prevention of unintended pregnancies is a public health objective; however, the profiles of male partners of women who choose to abort are relatively unexplored. OBJECTIVE: To investigate risk factors among men who have repeated experience of being the partner of a woman electing an induced abortion. METHODS: A questionnaire was used to collect information from 590 men recruited through their pregnant partner who applied for an abortion in Sweden during 2009. A binary logistic regression model assessed risk factors associated with repeated experience of abortion. RESULTS: One-third of the men had previous experience of a pregnant partner electing an induced abortion. Univariate analysis indicated these men were older, had a lower educational level and less emotional support, and were more often tobacco users than men for whom it was the first experience of a partner choosing to abort. Independent risk factors were being a victim of physical, psychological, or sexual violence or abuse over the past year (OR 2.62, 95% CI 1.36-5.08), unemployment or sick leave (OR 2.58, 95% CI 1.57-4.25), and having children (OR 2.00, 95% CI 1.22-3.28). The men suggested improved sex and relationship education in school and lower unemployment rates could prevent unintended pregnancies and abortions. CONCLUSIONS: Men with experience of repeat abortions present a picture of vulnerability that should be recognised in the prevention of unintended pregnancies. Increased work opportunities might be one important intervention to reduce the number of abortions. PMID- 22307997 TI - Framing the research agenda for sickle cell trait: building on the current understanding of clinical events and their potential implications. AB - Sickle Cell Trait (HbAS), the heterozygous state for the sickle hemoglobin beta globin gene is carried by as many as 100 million individuals including up to 25% of the population in some regions of the world (World Health Organization, Provisional agenda item 4.8, EB117/34 (22 December 2005) or World Health Organization, Provisional agenda item 11.4 (24 April 2006)). Persons with HbAS have some resistance to falciparum malaria infection in early childhood (Piel FB, Patil AP, Howes RE, et al., Nat Commun 2010;1104:1-7 and Aidoo M, Terlouw DJ, Kolczak M, et al., Lancet 2002;359:1311-1312) and as a result individuals with HbAS living in malarial endemic regions of Africa have a survival advantage over individuals with HbAA. Reports from the US emphasize possible health risks for individuals with HbAS including increased incidence of renal failure and malignancy, thromboembolic disorders, splenic infarction as a high altitude complication, and exercise-related sudden death. The National Heart, Lung, and Blood Institute, National Institutes of Health convened a workshop in Bethesda, Maryland on June 3-4, 2010, Framing the Research Agenda for Sickle Cell Trait, to review the clinical manifestations of HbAS, discuss the exercise-related sudden death reports in HbAS, and examine the public health, societal, and ethical implications of policies regarding HbAS. The goal of the workshop was to identify potential research questions to address knowledge gaps. PMID- 22307998 TI - Effect of different surface nanoroughness of titanium dioxide films on the growth of human osteoblast-like MG63 cells. AB - Cell behavior depends strongly on the physical and chemical properties of the material surface, for example, its chemistry and topography. The authors have therefore assessed the influence of materials of different chemical composition (i.e., glass substrates with and without TiO(2) films in anatase form) and different surface roughness (R(a) = 0, 40, 100, or 170 nm) on the adhesion, proliferation, and osteogenic differentiation of human osteoblast-like MG63 cells. On day 1 after seeding, the largest cell spreading area was found on flat TiO(2) films (R(a) = 0 nm). On TiO(2) films with R(a) = 170 nm, the cell spreading area was larger and the number of initially adhering cells was higher than the values on the corresponding uncoated glass. On day 3 after seeding, the cell number was higher on the TiO(2) films (R(a) = 0 and 40 nm) than on the corresponding glass substrates and the standard polystyrene dishes. On day 7, all TiO(2) films contained higher cell numbers than the corresponding glass substrates, and the cells on the TiO(2) films with R(a) = 40 and 100 nm also contained a higher concentration of beta-actin. These results indicate that TiO(2) coating had a positive influence on the adhesion and subsequent proliferation of MG63 cells. In addition, on all investigated materials, the cell population density achieved on day 7 decreased with increasing surface roughness. The concentration of osteocalcin, measured per mg of protein, was significantly lower in the cells on rougher TiO(2) films (R(a) = 100 and 170 nm) than in the cells on the polystyrene dishes. Thus, it can be concluded that the adhesion, growth, and phenotypic maturation of MG63 cells were controlled by the interplay between the material chemistry and surface topography, and were usually better on smoother and TiO(2)-coated surfaces than on rougher and uncoated glass substrates. PMID- 22307999 TI - Stage grouping in tumors of the ethmoid sinuses and the nasal cavity using the sixth edition of the UICC classification of malignant tumors. AB - BACKGROUND: The purpose of this study was to evaluate the prognostic impact of the sixth edition of the Union Internationale Contre le Cancer (UICC) classification and different TNM-based stage groupings for malignant tumors of the ethmoid sinuses and the nasal cavity. METHODS: We conducted a retrospective analysis of 98 patients with malignant tumors of the ethmoid sinuses and the nasal cavity between 1967 and 2003. The UICC classification of the sixth edition and the T and N Integer Score (TANIS) and Hart were tested for their prognostic significance. RESULTS: In univariate analysis, all stage groupings revealed discriminatory power for overall survival (OS; p < .05), however, in multivariate analysis only the UICC-stage grouping (p = .033) and the TANIS-8 scheme (p = .044) predicted OS. The TANIS did not have a better prognostic quality than the sixth edition of the UICC classification. CONCLUSION: The UICC-stage grouping of the sixth edition is a good prognostic index for malignant tumors of the ethmoid sinuses and the nasal cavity. PMID- 22308000 TI - Enhancing anisotropy barriers of dysprosium(III) single-ion magnets. PMID- 22308001 TI - A comparison of three theoretically important constructs: what accounts for symptoms of borderline personality disorder? AB - OBJECTIVE: Theories point to different mechanisms through which borderline personality disorder (BPD) symptoms may be developed and maintained: (a) emotion regulation dysfunction, (b) problematic relations, and (c) nonintegrated self. However, researchers have not investigated the relative contribution of these mechanisms simultaneously in accounting for the variance observed in BPD symptoms. METHOD: Drawing from university students and Internet users, 462 adults (63% female, 77% Caucasian) completed self-report measures of emotion regulation, interpersonal problems, sense of self, BPD symptoms, and depressive symptoms. RESULTS: All predictors were independently associated with BPD symptoms, with emotion regulation difficulties having the strongest relation. For high BPD individuals (N = 94), emotional regulation difficulties was the only predictor uniquely associated with BPD symptoms and interpersonal problems was the sole unique predictor of depressive symptoms. CONCLUSION: These results suggest that emotion regulation difficulties and interpersonal problems may be particularly problematic for those with high BPD symptoms in different ways. Implications and future directions are discussed. PMID- 22308002 TI - Learning Deformable Shape Manifolds. AB - We propose an approach to shape detection of highly deformable shapes in images via manifold learning with regression. Our method does not require shape key points be defined at high contrast image regions, nor do we need an initial estimate of the shape. We only require sufficient representative training data and a rough initial estimate of the object position and scale. We demonstrate the method for face shape learning, and provide a comparison to nonlinear Active Appearance Model. Our method is extremely accurate, to nearly pixel precision and is capable of accurately detecting the shape of faces undergoing extreme expression changes. The technique is robust to occlusions such as glasses and gives reasonable results for extremely degraded image resolutions. PMID- 22308003 TI - Resource seeking strategies of zoosporic true fungi in heterogeneous soil habitats at the microscale level. AB - Zoosporic true fungi have frequently been identified in samples from soil and freshwater ecosystems using baiting and molecular techniques. In fact some species can be components of the dominant groups of microorganisms in particular soil habitats. Yet these microorganisms have not yet been directly observed growing in soil ecosystems. Significant physical characteristics and features of the three-dimensional structures of soils which impact microorganisms at the microscale level are discussed. A thorough knowledge of soil structures is important for studying the distribution of assemblages of these fungi and understanding their ecological roles along spatial and temporal gradients. A number of specific adaptations and resource seeking strategies possibly give these fungi advantages over other groups of microorganisms in soil ecosystems. These include chemotactic zoospores, mechanisms for adhesion to substrates, rhizoids which can penetrate substrates in small spaces, structures which are resistant to environmental extremes, rapid growth rates and simple nutritional requirements. These adaptations are discussed in the context of the characteristics of soils ecosystems. Recent advances in instrumentation have led to the development of new and more precise methods for studying microorganisms in three-dimensional space. New molecular techniques have made identification of microbes possible in environmental samples. PMID- 22308004 TI - A molecular cryptosystem for images by DNA computing. PMID- 22308005 TI - The influence of substrate temperature on growth of para-sexiphenyl thin films on Ir{111} supported graphene studied by LEEM. AB - The growth of para-sexiphenyl (6P) thin films as a function of substrate temperature on Ir{111} supported graphene flakes has been studied in real-time with Low Energy Electron Microscopy (LEEM). Micro Low Energy Electron Diffraction (MULEED) has been used to determine the structure of the different 6P features formed on the surface. We observe the nucleation and growth of a wetting layer consisting of lying molecules in the initial stages of growth. Graphene defects - wrinkles - are found to be preferential sites for the nucleation of the wetting layer and of the 6P needles that grow on top of the wetting layer in the later stages of deposition. The molecular structure of the wetting layer and needles is found to be similar. As a result, only a limited number of growth directions are observed for the needles. In contrast, on the bare Ir{111} surface 6P molecules assume an upright orientation. The formation of ramified islands is observed on the bare Ir{111} surface at 320 K and 352 K, whereas at 405 K the formation of a continuous layer of upright standing molecules growing in a step flow like manner is observed. PMID- 22308006 TI - Total synthesis of (+/-)-isophellibiline. AB - The total synthesis of (+/-)-isophellibiline is described. This represents the first synthesis of a member of the nonaromatic homoerythrinan family of alkaloids. The tetracyclic ring system of the natural product was quickly assembled by a strategy that features a retrocycloaddition/cycloaddition reaction of an amidodioxin, an intramolecular Heck reaction and a 6pi-electrocyclic ring closure of a dienoic acid. PMID- 22308007 TI - Effects of vitamin E on bone turnover markers among US postmenopausal women. AB - Increased oxidative stress and inflammation resulting from aging and declining estrogen levels can lead to increased bone loss in postmenopausal women. Alpha tocopherol and gamma-tocopherol, the two predominant isomers of vitamin E, have antioxidant and anti-inflammatory properties, but their effects on bone metabolism have not been well studied in humans. We examined the associations between dietary and total (diet and supplements) alpha-tocopherol intake, serum alpha-tocopherol and gamma-tocopherol levels and their ratio, and bone turnover markers (BTMs) among postmenopausal women aged >=45 years. We used cross sectional data from the National Health and Nutrition Examination Survey 1999 2002. Multiple regression models with adjustments for relevant confounders were used to examine the associations between intake and serum levels of tocopherols, and serum bone-specific alkaline phosphatase (BAP), a biomarker of bone formation, and urinary N-telopeptides/creatinine (uNTx/Cr), a biomarker of bone resorption. The study sample included 497 postmenopausal women who were not taking estrogen, steroids, or osteoporosis medications, were free from kidney and liver disease, cancer, and rheumatoid arthritis, and were fasting >9 hours prior to examination. Participants had a mean age of 65.5 +/- 0.6 years and over 45% used vitamin E (alpha-tocopherol) supplements in the past month. Vitamin E supplement users had significantly lower serum gamma-tocopherol, higher serum alpha-tocopherol levels, and higher ratio of serum alpha-tocopherol to gamma tocopherol than nonusers. High serum gamma-tocopherol levels and low ratio of serum alpha-tocopherol to gamma-tocopherol were associated with increased BAP levels (p < 0.01 for both). There were no associations between any of the vitamin E variables and uNTx/Cr. In conclusion, we hypothesize that gamma-tocopherol may uncouple bone turnover, resulting in more bone formation than resorption. Vitamin E supplements in the form of alpha-tocopherol suppress serum gamma-tocopherol levels and may have negative effects on bone formation. Further research is needed to investigate the potential anabolic effect of gamma-tocopherol from food sources on bone. PMID- 22308008 TI - Preparation of organometallic ruthenium-arene-diaminotriazine complexes as binding agents to DNA. AB - The reactions of two diaminotriazine ligands 2,4-diamino-6-(2-pyridyl)-1,3,5 triazine (2-pydaT) and 6-phenyl-2,4-diamino-1,3,5-triazine (PhdaT) with ruthenium arene precursors led to a new family of ruthenium(II) compounds that were spectroscopically characterized. Four of the complexes were cationic, with the general formula [(eta(6)-arene)Ru(kappa(2)-N,N-2-pydaT)Cl]X (X=BF(4), TsO; arene=p-cymene: 1.BF(4), 1.TsO; arene=benzene: 2.BF(4), 2.TsO). The neutral cyclometalated complex [(eta(6)-p-cymene)Ru(kappa(2)-C,N-PhdaT*)Cl] (3) was also isolated. The structures of complexes 2.BF(4) and 3.H(2)O were determined by X ray diffraction. Complex 1.BF(4) underwent a partial reversible-aquation process in water. UV/Vis and NMR spectroscopic measurements showed that the reaction was hindered by the addition of NaCl and was pH-controlled in acidic solution. At pH 7.0 (sodium cacodylate) Ru-Cl complex 1.BF(4) was the only species present in solution, even at low ionic strength. However, in alkaline medium (KOH), complex 1.BF(4) underwent basic hydrolysis to afford a Ru-OH complex (5). Fluorimetric studies revealed that the interaction of complex 1.BF(4) with DNA was not straightforward; instead, its main features were closely linked to ionic strength and to the [DNA]/complex ratio. The bifunctional complex 1.BF(4) was capable of interacting concurrently through both its p-cymene and 2-pydaT groups. Cytotoxicity and genotoxicity studies showed that, contrary to the expected behavior, the complex species was biologically inactive; the formation of a Ru-OH complex could be responsible for such behavior. PMID- 22308009 TI - Primary neuroendocrine neoplasms of the larynx. A series of 4 cases reported and a review of the literature. AB - BACKGROUND: Neuroendocrine tumors are rare neoplasms arising from neural and epithelial origin. METHODS AND RESULTS: The case records of 4 patients with the diagnosis of neuroendocrine laryngeal tumor were retrospectively reviewed. In this analysis of our medical records, we describe a series of 4 men with neuroendocrine laryngeal tumors treated in our department since 1994, including the first extremely aggressive and lethal laryngeal paraganglioma reported in the English-language literature. We also discuss the classification, the macro and microscopical characteristics, clinical and pathologic findings, and treatment of these neoplasms. CONCLUSION: Although neuroendocrine laryngeal tumors account for approximately 1% of all neoplasms in the larynx, its majority represents very aggressive tumors showing a capacity for metastasis and portending poor outcome. PMID- 22308010 TI - Rituximab in combination with chemotherapy versus chemotherapy alone in HIV associated non-Hodgkin lymphoma: a pooled analysis of 15 prospective studies. AB - In HIV-positive patients with non-Hodgkin lymphoma (NHL), no benefit of adding rituximab to chemotherapy was seen in a randomized controlled trial (RCT). We performed a meta-analysis of prospective studies to ascertain outcomes in HIV positive NHL patients treated with chemotherapy (chemo) versus rituximab and chemo (R-chemo). A literature search through September 2011 was performed using the key search "(HIV OR AIDS) AND lymphoma". The main outcomes were overall response rate (ORR), complete response rate (CRR) and 2-year overall survival (OS) and are reported as non-adjusted odds ratio (OR). We identified 15 prospective studies including 1,060 HIV-positive NHL patients, 675 treated with chemo and 385 with R-chemo. There was a higher proportion of HAART in R-chemo patients (82% vs. 68%; p < 0.01) but there were no differences in proportion of patients with advanced stage or high/high-intermediate age-adjusted International Prognostic Index (aaIPI) scores. Meta-analysis showed the OR for ORR, CRR and 2 year OS in patients treated with R-chemo was 1.39 (95% CI 0.79-2.47; p = 0.26), 1.66 (95% CI 0.98-2.82; p = 0.06) and 2.19 (95% CI 1.68-2.86; p < 0.001), respectively. HIV-positive lymphoma patients treated with R-chemo had higher odds for CR and 2-year OS when compared to chemo but also had a higher proportion of HAART usage. PMID- 22308011 TI - Vitamin D deficiency is a predictor of reduced survival in patients with heart failure; vitamin D supplementation improves outcome. AB - AIMS: Vitamin D deficiency is a highly prevalent, global phenomenon. The prevalence in heart failure (HF) patients and its effect on outcome are less clear. We evaluated vitamin D levels and vitamin D supplementation in patients with HF and its effect on mortality. METHODS AND RESULTS: 25-Hydroxyvitamin D [25(OH)D] levels were evaluated in HF patients from a health maintenance organization (HMO), and compared them with those of the rest of the members of the HMO. Patients with HF (n = 3009) had a lower median 25(OH)D level compared with the control group (n = 46 825): 36.9 nmol/L (interquartile range 23.2-55.9) vs. 40.7 nmol/L (26.7-56.9), respectively, P < 0.00001. The percentage of patients with vitamin D deficiency [25(OH)D <25 nmol/L] was higher in patients with HF compared with the control group (28% vs. 22%, P < 0.00001). Only 8.8% of the HF patients had optimal 25(OH)D levels (>=75 nmol/L). Median clinical follow up was 518 days. Cox regression analysis demonstrated that vitamin D deficiency was an independent predictor of increased mortality in patients with HF [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.21-1.92, P < 0.001] and in the control group (HR 1.91, 95% CI 1.48-2.46, P < 0.00001). Vitamin D supplementation was independently associated with reduced mortality in HF patients (HR 0.68, 95% CI 0.54-0.85, P < 0.0001). Parameters associated with vitamin D deficiency in HF patients were decreased previous solar radiation exposure, body mass index, diabetes, female gender, pulse, and decreased calcium and haemoglobin levels. CONCLUSIONS: Vitamin D deficiency is highly prevalent in HF patients and is a significant predictor of reduced survival. Vitamin D supplementation was associated with improved outcome. PMID- 22308012 TI - Continuous-flow left ventricular assist device support in patients with advanced heart failure: points of interest for the daily management. AB - Today, continuous-flow left ventricular assist devices (cf-LVADs) are implanted more often in patients with end-stage heart failure. Because of greater durability they can be implanted for an extended period of time. As a result of increased numbers of patients on cf-LVAD support, healthcare professionals should be aware of the potential complications inherent to this therapy. Both bleeding and thrombosis may occur, and also complications related either to the device itself or to the ensuing altered haemodynamics, valvular pathology, and rhythm disturbances such as ventricular tachycardias and fibrillation. Accurate clinical evaluation, together with an electrocardiogram and, if necessary, combined with an echocardiogram, is obligatory in these situations. This review summarizes common complications complemented by a few clinical cases. PMID- 22308013 TI - Size-dependent cellular toxicity of silver nanoparticles. AB - Silver nanoparticles (AgNPs) have found a variety of uses including biomedical materials; however, studies of the cytotoxicity of AgNPs by size effects are only in the beginning stage. In this study, we examined the size-dependent cellular toxicity of AgNPs using three different characteristic sizes (~ 10, 50, and 100 nm) against several cell lines including MC3T3-E1 and PC12. The cytotoxic effect determined based on the cell viability, intracellular reactive oxygen species generation, lactate dehydrogenase release, ultrastructural changes in cell morphology, and upregulation of stress-related genes (ho-1 and MMP-3) was fairly size- and dose-dependent. In particular, AgNPs stimulated apoptosis in the MC3T3 E1 cells, but induced necrotic cell death in the PC12 cells. Furthermore, the smallest sized AgNPs (10 nm size) had a greater ability to induce apoptosis in the MC3T3-E1 cells than the other sized AgNPs (50 and 100 nm). These data suggest that the AgNPs-induced cytotoxic effects against tissue cells are particle size dependent, and thus, the particle size needs careful consideration in the design of the nanoparticles for biomedical uses. PMID- 22308014 TI - Estimating WAIS-IV indexes: proration versus linear scaling in a clinical sample. AB - OBJECTIVES: We compared the accuracy of proration and linear scaling for estimating Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV), Verbal Comprehension Index (VCI), and Perceptual Reasoning Index (PRI) composites from all possible two subtest combinations. The purpose was to provide practice relevant psychometric results in a clinical sample. DESIGN: The present investigation was an archival study that used mostly within-group comparisons. We analyzed WAIS-IV data of a clinical sample comprising 104 patients with brain damage and 37 with no known neurological impairment. RESULTS: In both clinical samples, actual VCI and PRI scores were highly correlated with estimated index scores based on proration and linear scaling (all rs >=.95). In the brain impaired sample, significant mean score differences between the actual and estimated composites were found in two comparisons, but these differences were less than three points; no other significant differences emerged. CONCLUSIONS: Overall, findings demonstrate that proration and linear scaling methods are feasible procedures when estimating actual Indexes. There was no advantage of one computational method over the other. PMID- 22308015 TI - Robust, Adaptive Functional Regression in Functional Mixed Model Framework. AB - Functional data are increasingly encountered in scientific studies, and their high dimensionality and complexity lead to many analytical challenges. Various methods for functional data analysis have been developed, including functional response regression methods that involve regression of a functional response on univariate/multivariate predictors with nonparametrically represented functional coefficients. In existing methods, however, the functional regression can be sensitive to outlying curves and outlying regions of curves, so is not robust. In this paper, we introduce a new Bayesian method, robust functional mixed models (R FMM), for performing robust functional regression within the general functional mixed model framework, which includes multiple continuous or categorical predictors and random effect functions accommodating potential between-function correlation induced by the experimental design. The underlying model involves a hierarchical scale mixture model for the fixed effects, random effect and residual error functions. These modeling assumptions across curves result in robust nonparametric estimators of the fixed and random effect functions which down-weight outlying curves and regions of curves, and produce statistics that can be used to flag global and local outliers. These assumptions also lead to distributions across wavelet coefficients that have outstanding sparsity and adaptive shrinkage properties, with great flexibility for the data to determine the sparsity and the heaviness of the tails. Together with the down-weighting of outliers, these within-curve properties lead to fixed and random effect function estimates that appear in our simulations to be remarkably adaptive in their ability to remove spurious features yet retain true features of the functions. We have developed general code to implement this fully Bayesian method that is automatic, requiring the user to only provide the functional data and design matrices. It is efficient enough to handle large data sets, and yields posterior samples of all model parameters that can be used to perform desired Bayesian estimation and inference. Although we present details for a specific implementation of the R-FMM using specific distributional choices in the hierarchical model, 1D functions, and wavelet transforms, the method can be applied more generally using other heavy-tailed distributions, higher dimensional functions (e.g. images), and using other invertible transformations as alternatives to wavelets. PMID- 22308016 TI - The effect of Kraussianone-2 (Kr2), a natural pyrano-isoflavone from Eriosema kraussianum, in an L-NAME- induced pre-eclamptic rat model. AB - This study aimed to investigate the effects of Kraussianone-2 (Kr2), a pyrano isoflavone isolated from the roots of Eriosema kraussianum N. E. Br. (Fabaceae) on various fetal and physiological parameters in pregnant, L-NAME treated Sprague Dawley rats. Twenty-four pregnant Sprague-Dawley dams were divided into three groups (n = 8), i.e. the control group (CON), the experimental control group (PRE), where the pre-eclampsia-like symptoms were induced using L-NAME, and the experimental group (EK2), where the pre-eclampsia-like symptoms were once again induced using L-NAME, however, these animals were treated with Kr2. On gestation day 20 the animals were sacrificed, at which time a laparotomy was performed and the number of live pups were counted and their corresponding birth and placental weights were recorded. Blood was also collected in heparin-coated tubes and the plasma samples were then analysed for specific variables using commercially available kits for rats. Kraussianone-2 administration decreased fetal mortality and demonstrated a trend toward increasing birth and placental weights in this model. Furthermore, Kr2 administration also reduced blood pressure amplification and decreased the plasma concentrations of two antiangiogenic factors, soluble fms-like tyrosine kinase1 (sFlt-1) and soluble endoglin (sEng). We speculate that Kr2, by improving uterine artery blood flow, results in improved fetal outcomes and decreased antiangiogenic factors in pregnant, L-NAME treated, Sprague-Dawley rats. PMID- 22308017 TI - Cu(I)-catalyzed (11)C carboxylation of boronic acid esters: a rapid and convenient entry to (11)C-labeled carboxylic acids, esters, and amides. AB - Rapid and direct: the carboxylation of boronic acid esters with (11)CO(2) provides [(11)C]carboxylic acids as a convenient entry into [(11)C]esters and [(11)C]amides. This conversion of boronates is tolerant to diverse functional groups (e.g., halo, nitro, or carbonyl). PMID- 22308018 TI - Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation. AB - Osteoclasts are thought to be solely responsible for the removal of bone matrix. However, we show here that osteocytes can also remove bone matrix by reversibly remodeling their perilacunar/canalicular matrix during the reproductive cycle. In contrast, no osteocytic remodeling was observed with experimental unloading despite similar degrees of bone loss. Gene array analysis of osteocytes from lactating animals revealed an elevation of genes known to be utilized by osteoclasts to remove bone, including tartrate-resistant acid phosphatase (TRAP) and cathepsin K, that returned to virgin levels upon weaning. Infusion of parathyroid hormone-related peptide (PTHrP), known to be elevated during lactation, induced TRAP activity and cathepsin K expression in osteocytes concurrent with osteocytic remodeling. Conversely, animals lacking the parathyroid hormone type 1 receptor (PTHR1) in osteocytes failed to express TRAP or cathepsin K or to remodel their osteocyte perilacunar matrix during lactation. These studies show that osteocytes remove mineralized matrix through molecular mechanisms similar to those utilized by osteoclasts. PMID- 22308019 TI - Synthesis and anti-oxidant activity of (5E,9E)-16-(substituted)-7,8-dihydro 16lambda(5) -dibenzo[d,l][1,3,7,10,2]dioxadiazaphosphacyclotridecine-16-ones. AB - A new class of biologically active 13-membered phosphorus-macroheterocycles (6a l) were conveniently synthesized from 1,2-bis(salicylidene amino)-phenylene (1), by treating with phosporusoxychloride (3) and followed by reacting with various aromatic thiols and amines (5f-l) in one path, and in another path 1 was directly treated with various phosphorodichloridates (2a-e) in the presence of triethylamine at 0-10 degrees C under N(2) atmosphere in THF. All the title compounds were confirmed by analytical and spectral data (IR, (1) H-, (13) C-, (31) P-NMR, and mass spectra) and screened for anti-oxidant activity. Among these compounds, 6k, 6e, and 6l containing nitro, fluoro, and chloro groups as substituents on the phenyl ring exhibited high anti-oxidant activity with effective inhibitory concentration (IC(50) ) values. PMID- 22308020 TI - Management of the neck and regional recurrence in squamous cell carcinoma of the maxillary alveolus and hard palate compared with other sites in the oral cavity. AB - BACKGROUND: The aim of this article was to assess the management of the neck and regional recurrence for squamous cell carcinoma of the maxillary alveolus and hard palate (n = 43) and compare that to the rest of the oral cancer sites (n = 465). METHODS: This is a retrospective report through database and case note review. RESULTS: The incidence of nodal metastases (pathologic node-positive necks added to regional recurrence for clinical N0 and pathologic N0) was 37% (16/43) for maxillary alveolus and hard palate compared with 40% (187/465) for the oral cavity in general. Regional recurrence occurred in 26% (11/43) in the maxillary alveolus and hard palate compared with 7% (31/465) in the remaining oral cavity sites (p = .001). CONCLUSIONS: Squamous cell carcinoma arising in the maxillary alveolus and hard palate has a similar risk of regional metastasis as the rest of the oral cavity, and a lower propensity for selective neck dissection is resulting in higher regional recurrence and lower survival rates. PMID- 22308021 TI - Influence of skin aging effects on the skin surface profile and the correlated distribution of topically applied sunscreens. AB - The surface profile of human skin influences characteristically the distribution pattern of topically applied formulations and consequently the efficacy of sunscreens. The volumes of furrows and the spectroscopically determined factors of inhomogeneity are investigated for three sunscreens. A clear correlation between both measurands exists. The average values for younger (<32 years) and older (>=51 years) volunteers do not show statistically significant differences. Systematic variations found for the individual values are due to a reduced elasticity of the skin with age improving the homogeneity of the sunscreen distribution. PMID- 22308022 TI - Unique disulfide bonds in epidermal growth factor (EGF) domains of beta3 affect structure and function of alphaIIbbeta3 and alphavbeta3 integrins in different manner. AB - The beta3 subunit of alphaIIbbeta3 and alphavbeta3 integrins contains four epidermal growth factor (EGF)-like domains. Each domain harbors four disulfide bonds of which one is unique for integrins. We previously discerned a regulatory role of the EGF-4 Cys-560-Cys-583 unique bond for alphaIIbbeta3 activation. In this study we further investigated the role of all four integrin unique bonds in both alphaIIbbeta3 and alphavbeta3. We created beta3 mutants harboring serine substitutions of each or both cysteines that disrupt the four unique bonds (Cys 437-Cys-457 in EGF-1, Cys-473-Cys-503 in EGF-2, Cys-523-Cys-544 in EGF-3, and Cys 560-Cys-583 in EGF-4) and transfected them into baby hamster kidney cells together with normal alphav or alphaIIb. Flow cytometry was used to measure surface expression of alphaIIbbeta3 and alphavbeta3 and their activity state by soluble fibrinogen binding. Most cysteine substitutions caused similarly reduced surface expression of both receptors. Disrupting all four unique disulfide bonds by single cysteine substitutions resulted in variable constitutive activation of alphaIIbbeta3 and alphavbeta3. In contrast, whereas double C437S/C457S and C473S/C503S mutations yielded constitutively active alphaIIbbeta3 and alphavbeta3, the C560S/C583S mutation did not, and the C523S/C544S mutation only yielded constitutively active alphaIIbbeta3. Activation of C523S/C544S alphavbeta3 mutant by activating antibody and dithiothreitol was also impaired. Molecular dynamics of C523S/C544S beta3 in alphaIIbbeta3 but not in alphavbeta3 displayed an altered stable conformation. Our findings indicate that unique disulfide bonds in beta3 differently affect the function of alphaIIbbeta3 and alphavbeta3 and suggest a free sulfhydryl-dependent regulatory role for Cys-560 Cys-583 in both alphaIIbbeta3 and alphavbeta3 and for Cys-523-Cys-544 only in alphavbeta3. PMID- 22308023 TI - Therapeutic effects of systemic administration of chaperone alphaB-crystallin associated with binding proinflammatory plasma proteins. AB - The therapeutic benefit of the small heat shock protein alphaB-crystallin (HspB5) in animal models of multiple sclerosis and ischemia is proposed to arise from its increased capacity to bind proinflammatory proteins at the elevated temperatures within inflammatory foci. By mass spectral analysis, a common set of ~70 ligands was precipitated by HspB5 from plasma from patients with multiple sclerosis, rheumatoid arthritis, and amyloidosis and mice with experimental allergic encephalomyelitis. These proteins were distinguished from other precipitated molecules because they were enriched in the precipitate as compared with their plasma concentrations, and they exhibited temperature-dependent binding. More than half of these ligands were acute phase proteins or members of the complement or coagulation cascades. Consistent with this proposal, plasma levels of HspB5 were increased in patients with multiple sclerosis as compared with normal individuals. The combination of the thermal sensitivity of the HspB5 combined with the high local concentration of these ligands at the site of inflammation is proposed to explain the paradox of how a protein believed to exhibit nonspecific binding can bind with some relative apparent selectivity to proinflammatory proteins and thereby modulate inflammation. PMID- 22308024 TI - MicroRNA-217 promotes ethanol-induced fat accumulation in hepatocytes by down regulating SIRT1. AB - Ethanol-mediated inhibition of hepatic sirtuin 1 (SIRT1) plays a crucial role in the pathogenesis of alcoholic fatty liver disease. Here, we investigated the underlying mechanisms of this inhibition by identifying a new hepatic target of ethanol action, microRNA-217 (miR-217). The role of miR-217 in the regulation of the effects of ethanol was investigated in cultured mouse AML-12 hepatocytes and in the livers of chronically ethanol-fed mice. In AML-12 hepatocytes and in mouse livers, chronic ethanol exposure drastically and specifically induced miR-217 levels and caused excess fat accumulation. Further studies revealed that overexpression of miR-217 in AML-12 cells promoted ethanol-mediated impairments of SIRT1 and SIRT1-regulated genes encoding lipogenic or fatty acid oxidation enzymes. More importantly, miR-217 impairs functions of lipin-1, a vital lipid regulator, in hepatocytes. Taken together, our novel findings suggest that miR 217 is a specific target of ethanol action in the liver and may present as a potential therapeutic target for treating human alcoholic fatty liver disease. PMID- 22308025 TI - Cardiac lineage protein-1 (CLP-1) regulates cardiac remodeling via transcriptional modulation of diverse hypertrophic and fibrotic responses and angiotensin II-transforming growth factor beta (TGF-beta1) signaling axis. AB - It is well known that the renin-angiotensin system contributes to left ventricular hypertrophy and fibrosis, a major determinant of myocardial stiffness. TGF-beta1 and renin-angiotensin system signaling alters the fibroblast phenotype by promoting its differentiation into morphologically distinct pathological myofibroblasts, which potentiates collagen synthesis and fibrosis and causes enhanced extracellular matrix deposition. However, the atrial natriuretic peptide, which is induced during left ventricular hypertrophy, plays an anti-fibrogenic and anti-hypertrophic role by blocking, among others, the TGF beta-induced nuclear localization of Smads. It is not clear how the hypertrophic and fibrotic responses are transcriptionally regulated. CLP-1, the mouse homolog of human hexamethylene bis-acetamide inducible-1 (HEXIM-1), regulates the pTEFb activity via direct association with pTEFb causing inhibition of the Cdk9 mediated serine 2 phosphorylation in the carboxyl-terminal domain of RNA polymerase II. It was recently reported that the serine kinase activity of Cdk9 not only targets RNA polymerase II but also the conserved serine residues of the polylinker region in Smad3, suggesting that CLP-1-mediated changes in pTEFb activity may trigger Cdk9-dependent Smad3 signaling that can modulate collagen expression and fibrosis. In this study, we evaluated the role of CLP-1 in vivo in induction of left ventricular hypertrophy in angiotensinogen-overexpressing transgenic mice harboring CLP-1 heterozygosity. We observed that introduction of CLP-1 haplodeficiency in the transgenic alpha-myosin heavy chain-angiotensinogen mice causes prominent changes in hypertrophic and fibrotic responses accompanied by augmentation of Smad3/Stat3 signaling. Together, our findings underscore the critical role of CLP-1 in remodeling of the genetic response during hypertrophy and fibrosis. PMID- 22308026 TI - Contribution of host nucleoporin 62 in HIV-1 integrase chromatin association and viral DNA integration. AB - HIV-1 integration is promoted by viral integrase (IN) and its cellular cofactors. The lens epithelium-derived growth factor (LEDGF/p75), an IN interacting cellular cofactor, has been shown to play an important role in HIV-1 chromatin targeting and integration. However, whether other cellular cofactors are also involved in viral replication steps is still elusive. Here, we show that nucleoporin 62 (Nup62) is a chromatin-bound protein and can specifically interact with HIV-1 IN in both soluble nuclear extract and chromatin-bound fractions. The knockdown of Nup62 by shRNA reduced the association of IN with host chromatin and significantly impaired viral integration and replication in HIV-1-susceptible cells. Furthermore, the expression of the IN-binding region of Nup62 in CD4(+) T cells significantly inhibited HIV-1 infection. Taken together, these results indicate that the cellular Nup62 is specifically recruited by HIV-1 IN and contribute to an efficient viral DNA integration. PMID- 22308027 TI - Interaction with ErbB4 promotes hypoxia-inducible factor-1alpha signaling. AB - The receptor-tyrosine kinase ErbB4 was identified as a direct regulator of hypoxia-inducible factor-1alpha (HIF-1alpha) signaling. Cleaved intracellular domain of ErbB4 directly interacted with HIF-1alpha in the nucleus, and stabilized HIF-1alpha protein in both normoxic and hypoxic conditions by blocking its proteasomal degradation. The mechanism of HIF stabilization was independent of VHL and proline hydroxylation but dependent on RACK1. ErbB4 activity was necessary for efficient HRE-driven promoter activity, transcription of known HIF 1alpha target genes, and survival of mammary carcinoma cells in vitro. In addition, mammary epithelial specific targeting of Erbb4 in the mouse significantly reduced the amount of HIF-1alpha protein in vivo. ERBB4 expression also correlated with the expression of HIF-regulated genes in a series of 4552 human normal and cancer tissue samples. These data demonstrate that soluble ErbB4 intracellular domain promotes HIF-1alpha stability and signaling via a novel mechanism. PMID- 22308028 TI - Increased unbound retinol-binding protein 4 concentration induces apoptosis through receptor-mediated signaling. AB - The increase of apo-/holo-retinol-binding protein 4 (RBP4) concentrations has been found in subjects with renal dysfunction and even in diabetic patients with microalbuminuria. Holo-RBP4 is recognized to possess cytoprotective function. Therefore, we supposed that the relative increase in apo-RBP4 might induce cell damage. In this study, we investigated the signal transduction that activated apoptosis in response to the increase of apo-/holo-RBP4 concentration. We found that increase of apo-/holo-RBP4 concentration ratio delayed the displacement of RBP4 with "stimulated by retinoic acid 6" (STRA6), enhanced Janus kinase 2 (JAK2)/STAT5 cascade, up-regulated adenylate cyclase 6 (AC6), increased cAMP, enhanced JNK1/p38 cascade, suppressed CRBP-I/RARalpha (cellular retinol-binding protein/retinoic acid receptor alpha) expression, and led to apoptosis in HK-2 and human umbilical vein endothelial cells. Furthermore, STRA6, JAK2, STAT5, JNK1, or p38 siRNA and cAMP-PKA inhibitor reversed the repression of CRBP I/RARalpha and apoptosis in apo-RBP4 stimulation. In conclusion, this study indicates that the increase of apo-/holo-RBP4 concentration may influence STRA6 signaling, finally causing apoptosis. PMID- 22308029 TI - Autophagy-related protein 32 acts as autophagic degron and directly initiates mitophagy. AB - Autophagy-related degradation selective for mitochondria (mitophagy) is an evolutionarily conserved process that is thought to be critical for mitochondrial quality and quantity control. In budding yeast, autophagy-related protein 32 (Atg32) is inserted into the outer membrane of mitochondria with its N- and C terminal domains exposed to the cytosol and mitochondrial intermembrane space, respectively, and plays an essential role in mitophagy. Atg32 interacts with Atg8, a ubiquitin-like protein localized to the autophagosome, and Atg11, a scaffold protein required for selective autophagy-related pathways, although the significance of these interactions remains elusive. In addition, whether Atg32 is the sole protein necessary and sufficient for initiation of autophagosome formation has not been addressed. Here we show that the Atg32 IMS domain is dispensable for mitophagy. Notably, when anchored to peroxisomes, the Atg32 cytosol domain promoted autophagy-dependent peroxisome degradation, suggesting that Atg32 contains a module compatible for other organelle autophagy. X-ray crystallography reveals that the Atg32 Atg8 family-interacting motif peptide binds Atg8 in a conserved manner. Mutations in this binding interface impair association of Atg32 with the free form of Atg8 and mitophagy. Moreover, Atg32 variants, which do not stably interact with Atg11, are strongly defective in mitochondrial degradation. Finally, we demonstrate that Atg32 forms a complex with Atg8 and Atg11 prior to and independent of isolation membrane generation and subsequent autophagosome formation. Taken together, our data implicate Atg32 as a bipartite platform recruiting Atg8 and Atg11 to the mitochondrial surface and forming an initiator complex crucial for mitophagy. PMID- 22308030 TI - Prolyl hydroxylase-dependent modulation of eukaryotic elongation factor 2 activity and protein translation under acute hypoxia. AB - Early adaptive responses to hypoxia are essential for cell survival, but their nature and underlying mechanisms are poorly known. We have studied the post transcriptional changes in the proteome of mammalian cells elicited by acute hypoxia and found that phosphorylation of eukaryotic elongation factor 2 (eEF2), a ribosomal translocase whose phosphorylation inhibits protein synthesis, is under the precise and reversible control of O(2) tension. Upon exposure to hypoxia, phosphorylation of eEF2 at Thr(56) occurred rapidly (<15 min) and resulted in modest translational arrest, a fundamental homeostatic response to hypoxia that spares ATP and thus facilitates cell survival. Acute inhibitory eEF2 phosphorylation occurred without ATP depletion or AMP kinase activation. Furthermore, eEF2 phosphorylation was mimicked by prolyl hydroxylase (PHD) inhibition with dimethyloxalylglycine or by selective PHD2 siRNA silencing but was independent of hypoxia-inducible factor alpha stabilization. Moreover, overexpression of PHD2 blocked hypoxic accumulation of phosphorylated eEF2. Therefore, our findings suggest that eEF2 phosphorylation status (and, as a consequence, translation rate) is controlled by PHD2 activity. They unravel a novel pathway for cell adaptation to hypoxia that could have pathophysiologic relevance in tissue ischemia and cancer. PMID- 22308031 TI - Structural insights into methyltransferase KsgA function in 30S ribosomal subunit biogenesis. AB - The assembly of the ribosomal subunits is facilitated by ribosome biogenesis factors. The universally conserved methyltransferase KsgA modifies two adjacent adenosine residues in the 3'-terminal helix 45 of the 16 S ribosomal RNA (rRNA). KsgA recognizes its substrate adenosine residues only in the context of a near mature 30S subunit and is required for the efficient processing of the rRNA termini during ribosome biogenesis. Here, we present the cryo-EM structure of KsgA bound to a nonmethylated 30S ribosomal subunit. The structure reveals that KsgA binds to the 30S platform with the catalytic N-terminal domain interacting with substrate adenosine residues in helix 45 and the C-terminal domain making extensive contacts to helix 27 and helix 24. KsgA excludes the penultimate rRNA helix 44 from adopting its position in the mature 30S subunit, blocking the formation of the decoding site and subunit joining. We suggest that the activation of methyltransferase activity and subsequent dissociation of KsgA control conformational changes in helix 44 required for final rRNA processing and translation initiation. PMID- 22308032 TI - Selenocysteine insertion sequence (SECIS)-binding protein 2 alters conformational dynamics of residues involved in tRNA accommodation in 80 S ribosomes. AB - Sec-tRNA(Sec) is site-specifically delivered at defined UGA codons in selenoprotein mRNAs. This recoding event is specified by the selenocysteine insertion sequence (SECIS) element and requires the selenocysteine (Sec)-specific elongation factor, eEFSec, and the SECIS binding protein, SBP2. Sec-tRNA(Sec) is delivered to the ribosome by eEFSec-GTP, but this ternary complex is not sufficient for Sec incorporation, indicating that its access to the ribosomal A site is regulated. SBP2 stably associates with ribosomes, and mutagenic analysis indicates that this interaction is essential for Sec incorporation. However, the ribosomal function of SBP2 has not been elucidated. To shed light on the functional relevance of the SBP2-ribosome interaction, we screened the functional centers of the 28 S rRNA in translationally competent 80 S ribosomes using selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE). We demonstrate that SBP2 specifically alters the reactivity of specific residues in Helix 89 (H89) and expansion segment 31 (ES31). These results are indicative of a conformational change in response to SBP2 binding. Based on the known functions of H89 during translation, we propose that SBP2 allows Sec incorporation by either promoting Sec-tRNA(Sec) accommodation into the peptidyltransferase center and/or by stimulating the ribosome-dependent GTPase activity of eEFSec. PMID- 22308033 TI - Structural dynamics of bacterial translation initiation factor IF2. AB - Bacterial translation initiation factor IF2 promotes ribosomal subunit association, recruitment, and binding of fMet-tRNA to the ribosomal P-site and initiation dipeptide formation. Here, we present the solution structures of GDP bound and apo-IF2-G2 of Bacillus stearothermophilus and provide evidence that this isolated domain binds the 50 S ribosomal subunit and hydrolyzes GTP. Differences between the free and GDP-bound structures of IF2-G2 suggest that domain reorganization within the G2-G3-C1 regions underlies the different structural requirements of IF2 during the initiation process. However, these structural signals are unlikely forwarded from IF2-G2 to the C-terminal fMet-tRNA binding domain (IF2-C2) because the connected IF2-C1 and IF2-C2 modules show completely independent mobility, indicating that the bacterial interdomain connector lacks the rigidity that was found in the archaeal IF2 homolog aIF5B. PMID- 22308034 TI - Stabilization of RNT-1 protein, runt-related transcription factor (RUNX) protein homolog of Caenorhabditis elegans, by oxidative stress through mitogen-activated protein kinase pathway. AB - RUNX proteins are evolutionarily conserved transcription factors known to be involved in various developmental processes. Here we report a new role for a RUNX protein: a role in stress response. We show that RNT-1, the Caenorhabditis elegans RUNX homolog, is constantly produced and degraded by the ubiquitination proteasome pathway in the intestine of the nematode. RNT-1 was rapidly stabilized by oxidative stress, and the rnt-1-mutant animals were more sensitive to oxidative stress, indicating that rapid RNT-1 stabilization is a defense response against the oxidative stress. The MAP kinase pathway is required for RNT-1 stabilization, and RNT-1 was phosphorylated by SEK-1/PMK-1 in vitro. ChIP sequencing analysis revealed a feedback loop mechanism of the MAP kinase pathway by the VHP-1 phosphatase in the RNT-1-mediated oxidative stress response. We propose that rnt-1 is regulated at the protein level for its role in the immediate response to environmental challenges in the intestine. PMID- 22308035 TI - Identification of mechanism that couples multisite phosphorylation of Yes associated protein (YAP) with transcriptional coactivation and regulation of apoptosis. AB - The transcriptional coactivator Yes-associated protein (YAP) has been implicated in tumorigenesis by regulating cell proliferation and apoptosis. YAP interacts with the transcription factor TEAD and is essential in mediating TEAD-dependent gene expression. Here we show that YAP is hyperphosphorylated and activated in response to genotoxic stress such as UV irradiation and cisplatin treatment. Using high resolution mobility shift assay for phosphorylated proteins, we identified multiple sites of phosphorylation induced by UV irradiation. Pretreatment with p38 and JNK inhibitors completely suppressed the mobility retardation of phosphorylated YAP in UV-irradiated cells. Co-immunoprecipitation experiments showed that the physical interaction of YAP with TEAD was markedly enhanced by UV irradiation or CDDP treatment but suppressed by pretreatment with p38 and JNK inhibitors. Similarly, pretreatment with p38 and JNK inhibitors suppressed the expression of YAP/TEAD target genes, which were elevated on exposure to genotoxic stress. Using phosphomimetic and phosphorylation-deficient YAP mutants, we showed that the coactivator activity of YAP correlated with its state of phosphorylation and sensitivity to cisplatin-induced apoptosis. Our results demonstrate that multisite phosphorylation of YAP induces YAP/TEAD dependent gene expression and provides a mechanism by which YAP regulates apoptosis differently depending on cellular context. PMID- 22308036 TI - Nrf2-dependent induction of proteasome and Pa28alphabeta regulator are required for adaptation to oxidative stress. AB - The ability to adapt to acute oxidative stress (e.g. H(2)O(2), peroxynitrite, menadione, and paraquat) through transient alterations in gene expression is an important component of cellular defense mechanisms. We show that such adaptation includes Nrf2-dependent increases in cellular capacity to degrade oxidized proteins that are attributable to increased expression of the 20 S proteasome and the Pa28alphabeta (11 S) proteasome regulator. Increased cellular levels of Nrf2, translocation of Nrf2 from the cytoplasm to the nucleus, and increased binding of Nrf2 to antioxidant response elements (AREs) or electrophile response elements (EpREs) in the 5'-untranslated region of the proteasome beta5 subunit gene (demonstrated by chromatin immunoprecipitation (or ChIP) assay) are shown to be necessary requirements for increased proteasome/Pa28alphabeta levels, and for maximal increases in proteolytic capacity and stress resistance; Nrf2 siRNA and the Nrf2 inhibitor retinoic acid both block these adaptive changes and the Nrf2 inducers DL-sulforaphane, lipoic acid, and curcumin all replicate them without oxidant exposure. The immunoproteasome is also induced during oxidative stress adaptation, contributing to overall capacity to degrade oxidized proteins and stress resistance. Two of the three immunoproteasome subunit genes, however, contain no ARE/EpRE elements, and Nrf2 inducers, inhibitors, and siRNA all have minimal effects on immunoproteasome expression during adaptation to oxidative stress. Thus, immunoproteasome appears to be (at most) minimally regulated by the Nrf2 signal transduction pathway. PMID- 22308037 TI - Distal heme pocket residues of B-type dye-decolorizing peroxidase: arginine but not aspartate is essential for peroxidase activity. AB - DypB from Rhodococcus jostii RHA1 is a bacterial dye-decolorizing peroxidase (DyP) that oxidizes lignin and Mn(II). Three residues interact with the iron bound solvent species in ferric DypB: Asn-246 and the conserved Asp-153 and Arg 244. Substitution of either Asp-153 or Asn-246 with alanine minimally affected the second order rate constant for Compound I formation (k(1) ~ 10(5) M(-1)s(-1)) and the specificity constant (k(cat)/K(m)) for H(2)O(2). Even in the D153A/N246A double variant, these values were reduced less than 30-fold. However, these substitutions dramatically reduced the stability of Compound I (t(1/2) ~ 0.13 s) as compared with the wild-type enzyme (540 s). By contrast, substitution of Arg 244 with leucine abolished the peroxidase activity, and heme iron of the variant showed a pH-dependent transition from high spin (pH 5) to low spin (pH 8.5). Two variants were designed to mimic the plant peroxidase active site: D153H, which was more than an order of magnitude less reactive with H(2)O(2), and N246H, which had no detectable peroxidase activity. X-ray crystallographic studies revealed that structural changes in the variants are confined to the distal heme environment. The data establish an essential role for Arg-244 in Compound I formation in DypB, possibly through charge stabilization and proton transfer. The principle roles of Asp-153 and Asn-246 appear to be in modulating the subsequent reactivity of Compound I. These results expand the range of residues known to catalyze Compound I formation in heme peroxidases. PMID- 22308038 TI - Crystal structure of human cytochrome P450 2D6 with prinomastat bound. AB - Human cytochrome P450 2D6 contributes to the metabolism of >15% of drugs used in clinical practice. This study determined the structure of P450 2D6 complexed with a substrate and potent inhibitor, prinomastat, to 2.85 A resolution by x-ray crystallography. Prinomastat binding is well defined by electron density maps with its pyridyl nitrogen bound to the heme iron. The structure of ligand-bound P450 2D6 differs significantly from the ligand-free structure reported for the P450 2D6 Met-374 variant (Protein Data Bank code 2F9Q). Superposition of the structures reveals significant differences for beta sheet 1, helices A, F, F', G", G, and H as well as the helix B-C loop. The structure of the ligand complex exhibits a closed active site cavity that conforms closely to the shape of prinomastat. The closure of the open cavity seen for the 2F9Q structure reflects a change in the direction and pitch of helix F and introduction of a turn at Gly 218, which is followed by a well defined helix F' that was not observed in the 2F9Q structure. These differences reflect considerable structural flexibility that is likely to contribute to the catalytic versatility of P450 2D6, and this new structure provides an alternative model for in silico studies of substrate interactions with P450 2D6. PMID- 22308040 TI - Assembly and channel opening of outer membrane protein in tripartite drug efflux pumps of Gram-negative bacteria. AB - Gram-negative bacteria are capable of expelling diverse xenobiotic substances from within the cell by use of three-component efflux pumps in which the energy activated inner membrane transporter is connected to the outer membrane channel protein via the membrane fusion protein. In this work, we describe the crystal structure of the membrane fusion protein MexA from the Pseudomonas aeruginosa MexAB-OprM pump in the hexameric ring arrangement. Electron microscopy study on the chimeric complex of MexA and the outer membrane protein OprM reveals that MexA makes a tip-to-tip interaction with OprM, which suggests a docking model for MexA and OprM. This docking model agrees well with genetic results and depicts detailed interactions. Opening of the OprM channel is accompanied by the simultaneous exposure of a protein structure resembling a six-bladed cogwheel, which intermeshes with the complementary cogwheel structure in the MexA hexamer. Taken together, we suggest an assembly and channel opening model for the MexAB OprM pump. This study provides a better understanding of multidrug resistance in Gram-negative bacteria. PMID- 22308039 TI - Integrin beta4 regulates SPARC protein to promote invasion. AB - The alpha6beta4 integrin (referred to as "beta4" integrin) is a receptor for laminins that promotes carcinoma invasion through its ability to regulate key signaling pathways and cytoskeletal dynamics. An analysis of published Affymetrix GeneChip data to detect downstream effectors involved in beta4-mediated invasion of breast carcinoma cells identified SPARC, or secreted protein acidic and rich in cysteine. This glycoprotein has been shown to play an important role in matrix remodeling and invasion. Our analysis revealed that manipulation of beta4 integrin expression and signaling impacted SPARC expression and that SPARC facilitates beta4-mediated invasion. Expression of beta4 in beta4-deficient cells reduced the expression of a specific microRNA (miR-29a) that targets SPARC and impedes invasion. In cells that express endogenous beta4, miR-29a expression is low and beta4 ligation facilitates the translation of SPARC through a TOR dependent mechanism. The results obtained in this study demonstrate that beta4 can regulate SPARC expression and that SPARC is an effector of beta4-mediated invasion. They also highlight a potential role for specific miRNAs in executing the functions of integrins. PMID- 22308041 TI - Absence of acute inhibitory effect of insulin on chylomicron production in type 2 diabetes. AB - OBJECTIVE: Overproduction of intestinally derived apoB-48-containing triglyceride rich lipoproteins (TRLs) (chylomicrons) has recently been described in type 2 diabetes, as is known for hepatic TRL-apoB-100 (very-low-density lipoprotein) production. Furthermore, insulin acutely inhibits both intestinal and hepatic TRL production, whereas this acute inhibitory effect on very-low-density lipoprotein production is blunted in type 2 diabetes. It is not currently known whether this acute effect on chylomicron production is similarly blunted in humans with type 2 diabetes. METHODS AND RESULTS: We investigated the effect of acute hyperinsulinemia on TRL metabolism in 18 type 2 diabetic men using stable isotope methodology. Each subject underwent 1 control (saline infusion [SAL]) lipoprotein turnover study followed by a second study, under 1 of the 3 following clamp conditions: (1) hyperinsulinemic-euglycemic, (2) hyperinsulinemic-hyperglycemic, or (3) hyperinsulinemic-euglycemic plus intralipid and heparin. TRL-apoB-48 and TRL-apoB-100 production and clearance rates were not different between SAL and clamp and between the different clamp conditions, except for significantly lower TRL-apoB-100 clearance and production rates in hyperinsulinemic-euglycemic plus intralipid and heparin clamp compared with SAL. CONCLUSIONS: This is the first demonstration in individuals with type 2 diabetes that chylomicron production is resistant to the normal acute suppressive effect of insulin. This phenomenon may contribute to the highly prevalent dyslipidemia of type 2 diabetes and potentially to atherosclerosis. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00950209. PMID- 22308042 TI - Intravascular optical coherence tomography detection of atherosclerosis and inflammation in murine aorta. AB - OBJECTIVE: The goal of this study was to evaluate the feasibility of imaging the aorta of apolipoprotein E-deficient (ApoE(-/-)) mice for the detection of atherosclerosis and macrophages using optical coherence tomography (OCT) compared with histology. METHODS AND RESULTS: Atherosclerosis was induced by high-fat diet in 7-week-old ApoE(-/-) mice for 10 (n=7) and 22 (n=7) weeks. Nine-week-old ApoE( /-) mice (n=7) fed a standard chow diet were used as controls. OCT images of a 10 mm descending aorta in situ were performed in 4 mice for each, and plaque and macrophages were determined at 0.5-mm intervals. Automated detection and quantification of macrophages were performed independently using a customized algorithm. Coregistered histological cross-sections were stained with hematoxylin eosin, Mac-3, and von Kossa. Three mice in each group had en face OCT imaging to detect macrophages, which were compared with lipid-positive area with Sudan IV. OCT images were successfully acquired in all mice. OCT and histology were able to discriminate macrophages and plaque among the 3 groups and showed excellent correlation for (1) visual detection of plaque (r=0.98) and macrophages (r=0.93), (2) automated detection and quantification of macrophages by OCT versus Mac-3 positive area (r=0.92), and (3) en face OCT detection of macrophages versus Sudan IV-positive area (r=0.92). CONCLUSIONS: Murine intra-aortic OCT is feasible and shows excellent correlation with histology for detection of atherosclerotic plaque and macrophages. PMID- 22308043 TI - In vivo targeting of inflammation-associated myeloid-related protein 8/14 via gadolinium immunonanoparticles. AB - OBJECTIVE: Myeloid-related protein (Mrp) 8/14 complex (is a highly expressed extracellularly secreted protein, implicated in atherosclerosis. In this study, we evaluated the feasibility of targeting Mrp in vivo through synthetic immuno nanoprobes. METHODS AND RESULTS: Anti-Mrp-14 and nonspecific IgG-conjugated gadolinium nanoprobes (aMrp-) were synthesized and characterized. Pharmacokinetics and vascular targeting via MRI of the formulations were assessed in vivo in high fat-fed apolipoprotein E deficient (ApoE(-/-)), ApoE(-/-)/Mrp14( /-) (double knockout) and chow-fed wild-type (C57BL/6) mice. Bone marrow-derived myeloid progenitor cells were isolated from both ApoE(-/-) and double knockout mice, differentiated to macrophages, and were treated with LPS, with or without Mrp8, Mrp14, or Mrp8/14; conditioned media was used for in vitro studies. Mrp activated cells secreted significant amounts of proinflammatory cytokines, which was abolished by pretreatment with aMrp-NP. We show in vitro that aMrp-NP binds endothelial cells previously treated with conditioned media containing Mrp8/14. MRI following intravenous delivery of aMrp-NP revealed prolonged and substantial delineation of plaque in ApoE(-/-) but not double knockout or wild-type animals. Nonspecific IgG-conjugated gadolinium nanoprobe-injected animals in all groups did not show vessel wall enhancement. Flow-cytometric analysis of aortic digesta revealed that aMrp-NP present in Ly-6G(+), CD11b(+), CD11c(+), and CD31(+) cells in ApoE(-/-) but not in double knockout animals. CONCLUSIONS: Targeted imaging with aMrp-NP demonstrates enhancement of plaque with binding to inflammatory cells and reduction in inflammation. This strategy has promise as a theranostic approach for atherosclerosis. PMID- 22308046 TI - Taxonomy of Penicillium section Citrina. AB - Species of Penicillium section Citrina have a worldwide distribution and occur commonly in soils. The section is here delimited using a combination of phenotypic characters and sequences of the nuclear ribosomal RNA gene operon, including the internal transcribed spacer regions ITS1 and ITS2, the 5.8S nrDNA (ITS) and partial RPB2 sequences. Species assigned to section Citrina share the production of symmetrically biverticillate conidiophores, flask shaped phialides (7.0-9.0 MUm long) and relatively small conidia (2.0-3.0 MUm diam). Some species can produce greyish-brown coloured cleistothecia containing flanged ascospores. In the present study, more than 250 isolates presumably belonging to section Citrina were examined using a combined analysis of phenotypic and physiological characters, extrolite profiles and ITS, beta-tubulin and/or calmodulin sequences. Section Citrina includes 39 species, and 17 of those are described here as new. The most important phenotypic characters for distinguishing species are growth rates and colony reverse colours on the agar media CYA, MEA and YES; shape, size and ornamentation of conidia and the production of sclerotia or cleistothecia. Temperature-growth profiles were made for all examined species and are a valuable character characters for species identification. Species centered around P. citrinum generally have a higher maximum growth temperature (33-36 degrees C) than species related to P. westlingii (27-33 degrees C). Extrolite patterns and partial calmodulin and beta-tubulin sequences can be used for sequence based identification and resolved all species. In contrast, ITS sequences were less variable and only 55 % of the species could be unambiguously identified with this locus. TAXONOMIC NOVELTIES: Penicillium argentinense Houbraken, Frisvad & Samson, P. atrofulvum Houbraken, Frisvad & Samson, P. aurantiacobrunneum Houbraken, Frisvad & Samson, P. cairnsense Houbraken, Frisvad & Samson, P. christenseniae Houbraken, Frisvad & Samson, P. copticola Houbraken, Frisvad & Samson, P. cosmopolitanum Houbraken, Frisvad & Samson, P. neomiczynskii Cole, Houbraken, Frisvad & Samson, P. nothofagi Houbraken, Frisvad & Samson, P. pancosmium Houbraken, Frisvad & Samson, P. pasqualense Houbraken, Frisvad & Samson, P. quebecense Seifert, Houbraken, Frisvad & Samson, P. raphiae Houbraken, Frisvad & Samson, P. terrigenum Seifert, Houbraken, Frisvad & Samson, P. ubiquetum Houbraken, Frisvad & Samson, P. vancouverense Houbraken, Frisvad & Samson, P. wellingtonense Cole, Houbraken, Frisvad & Samson. PMID- 22308045 TI - Phylogeny of Penicillium and the segregation of Trichocomaceae into three families. AB - Species of Trichocomaceae occur commonly and are important to both industry and medicine. They are associated with food spoilage and mycotoxin production and can occur in the indoor environment, causing health hazards by the formation of beta glucans, mycotoxins and surface proteins. Some species are opportunistic pathogens, while others are exploited in biotechnology for the production of enzymes, antibiotics and other products. Penicillium belongs phylogenetically to Trichocomaceae and more than 250 species are currently accepted in this genus. In this study, we investigated the relationship of Penicillium to other genera of Trichocomaceae and studied in detail the phylogeny of the genus itself. In order to study these relationships, partial RPB1, RPB2 (RNA polymerase II genes), Tsr1 (putative ribosome biogenesis protein) and Cct8 (putative chaperonin complex component TCP-1) gene sequences were obtained. The Trichocomaceae are divided in three separate families: Aspergillaceae, Thermoascaceae and Trichocomaceae. The Aspergillaceae are characterised by the formation flask-shaped or cylindrical phialides, asci produced inside cleistothecia or surrounded by Hulle cells and mainly ascospores with a furrow or slit, while the Trichocomaceae are defined by the formation of lanceolate phialides, asci borne within a tuft or layer of loose hyphae and ascospores lacking a slit. Thermoascus and Paecilomyces, both members of Thermoascaceae, also form ascospores lacking a furrow or slit, but are differentiated from Trichocomaceae by the production of asci from croziers and their thermotolerant or thermophilic nature. Phylogenetic analysis shows that Penicillium is polyphyletic. The genus is re-defined and a monophyletic genus for both anamorphs and teleomorphs is created (Penicillium sensu stricto). The genera Thysanophora, Eupenicillium, Chromocleista, Hemicarpenteles and Torulomyces belong in Penicilliums. str. and new combinations for the species belonging to these genera are proposed. Analysis of Penicillium below genus rank revealed the presence of 25 clades. A new classification system including both anamorph and teleomorph species is proposed and these 25 clades are treated here as sections. An overview of species belonging to each section is presented. TAXONOMIC NOVELTIES: New sections, all in Penicillium: sect. Sclerotiora Houbraken & Samson, sect. Charlesia Houbraken & Samson, sect. Thysanophora Houbraken & Samson,sect. Ochrosalmonea Houbraken & Samson, sect. Cinnamopurpurea Houbraken & Samson, Fracta Houbraken & Samson, sect. Stolkia Houbraken & Samson, sect. Gracilenta Houbraken & Samson, sect. Citrina Houbraken & Samson, sect. Turbata Houbraken & Samson, sect. Paradoxa Houbraken & Samson, sect. Canescentia Houbraken & Samson. New combinations:Penicillium asymmetricum (Subramanian & Sudha) Houbraken & Samson, P. bovifimosum (Tuthill & Frisvad) Houbraken & Samson, P. glaucoalbidum (Desmazieres) Houbraken & Samson, P. laeve (K. Ando & Manoch) Houbraken & Samson, P. longisporum (Kendrick) Houbraken & Samson, P. malachiteum (Yaguchi & Udagawa) Houbraken & Samson, P. ovatum (K. Ando & Nawawi) Houbraken & Samson, P. parviverrucosum (K. Ando & Pitt) Houbraken & Samson, P. saturniforme (Wang & Zhuang) Houbraken & Samson, P. taiwanense (Matsushima) Houbraken & Samson. New names:Penicillium coniferophilum Houbraken & Samson, P. hennebertii Houbraken & Samson, P. melanostipe Houbraken & Samson, P. porphyreum Houbraken & Samson. PMID- 22308044 TI - Sphingosine-1-phosphate receptor 3 promotes neointimal hyperplasia in mouse iliac femoral arteries. AB - OBJECTIVE: The objective of this study was to define a role for sphingosine-1 phosphate receptor 3 (S1PR3) in intimal hyperplasia. METHODS AND RESULTS: A denudation model of the iliac-femoral artery in wild-type and S1PR3-null mice was used to define a role for S1PR3 in the arterial injury response because we found in humans and mice that expression of S1PR3 was higher in these arteries compared with carotid arteries. At 28 days after surgery, wild-type arteries formed significantly larger lesions than S1PR3-null arteries. Bromodeoxyuridine labeling experiments demonstrated that on injury, wild-type arteries exhibited higher medial as well as intimal proliferation than S1PR3-null arteries. Because S1PR3 expression in vitro was low, we expressed S1PR3 in S1PR3-null smooth muscle cells (SMCs) using retroviral-mediated gene transfer to study the effects of S1PR3 on cell functions and signaling. SMCs expressing S1PR3, but not vector-transfected controls, responded to sphingosine-1-phosphate stimulation with activation of Rac, Erk, and Akt. SMCs expressing S1PR3 also migrated more. CONCLUSIONS: In humans and mice, S1PR3 expression was higher in iliac-femoral arteries compared with carotid arteries. S1PR3 promoted neointimal hyperplasia on denudation of iliac-femoral arteries in mice, likely by stimulating cell migration and proliferation through activation of signaling pathways involving Erk, Akt, and Rac. PMID- 22308047 TI - A taxonomic and phylogenetic revision of the Penicillium sclerotiorum complex. AB - The morphological concept of Penicillium sclerotiorum (subgenus Aspergilloides) includes strains with monoverticillate, vesiculate conidiophores, and vivid orange to red colony colours, with colourful sclerotia sometimes produced. Multigene phylogenetic analyses with the nuclear ribosomal internal transcribed spacer (ITS) region, cytochrome c oxidase subunit 1 (cox1), beta-tubulin (benA), translation elongation factor 1-alpha (tef1-alpha), and calmodulin (cmd), reveal that the P. sclerotiorum morphospecies is a complex of seven phylogenetically distinct species, three of which were recently described, namely P. guanacastense, P. mallochii, and P. viticola. Three previously unidentified species are described here as P. cainii, P. jacksonii, and P. johnkrugii. The phylogenetic species are morphologically similar, but differ in combinations of colony characters, sclerotium production, conidiophore stipe roughening and branching, and conidial shape. Ecological characters and differences in geographical distribution further characterise some of the species, but increased sampling is necessary to confirm these differences. The fungal DNA barcode, the ITS, and the animal DNA barcode, cox1, have lower species resolving ability in our phylogenetic analyses, but still allow identification of all the species. Tef1-alpha and cmd were superior in providing fully resolved, statistically well supported phylogenetic trees for this species complex, whereas benA resolved all species but had some issues with paraphyly. Penicilliumadametzioides and P. multicolor, considered synonyms of P. sclerotiorum by some previous authors, do not belong to the P. sclerotiorum complex. TAXONOMIC NOVELTIES: New species:Penicillium cainii K.G. Rivera, Malloch & Seifert, P. jacksonii K.G. Rivera, Houbraken & Seifert, P. johnkrugii K.G. Rivera, Houbraken & Seifert. PMID- 22308048 TI - Phylogeny and nomenclature of the genus Talaromyces and taxa accommodated in Penicillium subgenus Biverticillium. AB - The taxonomic history of anamorphic species attributed to Penicillium subgenus Biverticillium is reviewed, along with evidence supporting their relationship with teleomorphic species classified in Talaromyces. To supplement previous conclusions based on ITS, SSU and/or LSU sequencing that Talaromyces and subgenus Biverticillium comprise a monophyletic group that is distinct from Penicillium at the generic level, the phylogenetic relationships of these two groups with other genera of Trichocomaceae was further studied by sequencing a part of the RPB1 (RNA polymerase II largest subunit) gene. Talaromyces species and most species of Penicillium subgenus Biverticilliumsensu Pitt reside in a monophyletic clade distant from species of other subgenera of Penicillium. For detailed phylogenetic analysis of species relationships, the ITS region (incl. 5.8S nrDNA) was sequenced for the available type strains and/or representative isolates of Talaromyces and related biverticillate anamorphic species. Extrolite profiles were compiled for all type strains and many supplementary cultures. All evidence supports our conclusions that Penicillium subgenus Biverticillium is distinct from other subgenera in Penicillium and should be taxonomically unified with the Talaromyces species that reside in the same clade. Following the concepts of nomenclatural priority and single name nomenclature, we transfer all accepted species of Penicillium subgenus Biverticillium to Talaromyces. A holomorphic generic diagnosis for the expanded concept of Talaromyces, including teleomorph and anamorph characters, is provided. A list of accepted Talaromyces names and newly combined Penicillium names is given. Species of biotechnological and medical importance, such as P. funiculosum and P. marneffei, are now combined in Talaromyces. Excluded species and taxa that need further taxonomic study are discussed. An appendix lists other generic names, usually considered synonyms of Penicillium sensu lato that were considered prior to our adoption of the name Talaromyces. TAXONOMIC NOVELTIES: Taxonomic novelties:New species - Talaromyces apiculatus Samson, Yilmaz & Frisvad, sp. nov. New combinationsand names - Talaromyces aculeatus (Raper & Fennell) Samson, Yilmaz, Frisvad & Seifert, T. albobiverticillius (H.-M. Hsieh, Y.-M. Ju & S.-Y. Hsieh) Samson, Yilmaz, Frisvad & Seifert, T. allahabadensis (B.S. Mehrotra & D. Kumar) Samson, Yilmaz & Frisvad, T. aurantiacus (J.H. Mill., Giddens & A.A. Foster) Samson, Yilmaz, & Frisvad, T. boninensis (Yaguchi & Udagawa) Samson, Yilmaz, & Frisvad, T. brunneus (Udagawa) Samson, Yilmaz & Frisvad, T. calidicanius (J.L. Chen) Samson, Yilmaz & Frisvad, T. cecidicola (Seifert, Hoekstra & Frisvad) Samson, Yilmaz, Frisvad & Seifert, T. coalescens (Quintan.) Samson, Yilmaz & Frisvad, T. dendriticus (Pitt) Samson, Yilmaz, Frisvad & Seifert, T. diversus (Raper & Fennell) Samson, Yilmaz & Frisvad, T. duclauxii (Delacr.) Samson, Yilmaz, Frisvad & Seifert, T. echinosporus (Nehira) Samson, Yilmaz & Frisvad, comb. nov. T. erythromellis (A.D. Hocking) Samson, Yilmaz, Frisvad & Seifert, T. funiculosus (Thom) Samson, Yilmaz, Frisvad & Seifert, T. islandicus (Sopp) Samson, Yilmaz, Frisvad & Seifert, T. loliensis (Pitt) Samson, Yilmaz & Frisvad, T. marneffei (Segretain, Capponi & Sureau) Samson, Yilmaz, Frisvad & Seifert, T. minioluteus (Dierckx) Samson, Yilmaz, Frisvad & Seifert, T. palmae (Samson, Stolk & Frisvad) Samson, Yilmaz, Frisvad & Seifert, T. panamensis (Samson, Stolk & Frisvad) Samson, Yilmaz, Frisvad & Seifert, T. paucisporus (Yaguchi, Someya & Udagawa) Samson & Houbraken T. phialosporus (Udagawa) Samson, Yilmaz & Frisvad, T. piceus (Raper & Fennell) Samson, Yilmaz, Frisvad & Seifert, T. pinophilus (Hedgcock) Samson, Yilmaz, Frisvad & Seifert, T. pittii (Quintan.) Samson, Yilmaz, Frisvad & Seifert, T. primulinus (Pitt) Samson, Yilmaz & Frisvad, T. proteolyticus (Kamyschko) Samson, Yilmaz & Frisvad, T. pseudostromaticus (Hodges, G.M. Warner, Rogerson) Samson, Yilmaz, Frisvad & Seifert, T. purpurogenus (Stoll) Samson, Yilmaz, Frisvad & Seifert, T. rademirici (Quintan.) Samson, Yilmaz & Frisvad, T. radicus (A.D. Hocking & Whitelaw) Samson, Yilmaz, Frisvad & Seifert, T. ramulosus (Visagie & K. Jacobs) Samson, Yilmaz, Frisvad & Seifert, T. rubicundus (J.H. Mill., Giddens & A.A. Foster) Samson, Yilmaz, Frisvad & Seifert, T. rugulosus (Thom) Samson, Yilmaz, Frisvad & Seifert, T. sabulosus (Pitt & A.D. Hocking) Samson, Yilmaz & Frisvad, T. siamensis (Manoch & C. Ramirez) Samson, Yilmaz & Frisvad, T. sublevisporus (Yaguchi & Udagawa) Samson, Yilmaz & Frisvad, T. variabilis (Sopp) Samson, Yilmaz, Frisvad & Seifert, T. varians (G. Sm.) Samson, Yilmaz & Frisvad, T. verruculosus (Peyronel) Samson, Yilmaz, Frisvad & Seifert, T. viridulus Samson, Yilmaz & Frisvad. PMID- 22308049 TI - Magnetically interacting low dimensional Ni-nanostructures within porous silicon. AB - Electrodeposition of ferromagnetic metals, a common method to fabricate magnetic nanostructures, is used for the incorporation of Ni structures into the pores of porous silicon templates. The porous silicon is fabricated in various morphologies with average pore-diameters between 40 and 95 nm and concomitant pore-distances between 60 and 40 nm. The metal nanostructures are deposited with different geometries as spheres, ellipsoids or wires influenced by the deposition process parameters. Furthermore small Ni-particles with diameters between 3 and 6 nm can be deposited on the walls of the porous silicon template forming a metal tube. Analysis of this tube-like arrangement by transmission electron microscopy (TEM) shows that the distribution of the Ni-particles is quite narrow, which means that the distance between the particles is smaller than 10 nm. Such a close arrangement of the Ni-particles assures magnetic interactions between them. Due to their size these small Ni-particles are superparamagnetic but dipolar coupling between them results in a ferromagnetic behavior of the whole system. Thus a semiconducting/ferromagnetic hybrid material with a broad range of magnetic properties can be fabricated. Furthermore this composite is an interesting candidate for silicon based applications and the compatibility with today's process technology. PMID- 22308050 TI - Thinking About Better Speech: Mental Practice for Stroke-Induced Motor Speech Impairments. AB - BACKGROUND: Mental practice (MP) is a mind-body technique in which physical movements are cognitively rehearsed. It has shown efficacy in reducing the severity of a number of neurological impairments. AIMS: In the present review, we highlight recent developments in MP research, and the basis for MP use after stroke-induced motor speech disorders. MAIN CONTRIBUTION: In this review, we: (a) propose a novel conceptual model regarding the development of learned nonuse in people with motor speech impairments; (b) review the rationale and efficacy of MP for reducing the severity of stroke-induced impairments; (c) review evidence demonstrating muscular and neural activations during and following MP use; (d) review evidence showing that MP increases skill acquisition, use, and function in stroke; (e) review literature regarding neuroplasticity after stroke, including MP-induced neuroplasticity and the neural substrates underlying motor and language reacquisition; and (f) based on the above, review the rationale and clinical application of MP for stroke-induced motor speech impairments. CONCLUSIONS: Support for MP use includes decades of MP neurobiological and behavioral efficacy data in a number of populations. Most recently, these data have expanded to the application of MP in neurological populations. Given increasingly demanding managed care environments, efficacious strategies that can be easily administered are needed. We also encounter clinicians who aspire to use MP, but their protocols do not contain several of the elements shown to be fundamental to effective MP implementation. Given shortfalls of some conventional aphasia and motor speech rehabilitative techniques, and uncertainty regarding optimal MP implementation, this paper introduces the neurophysiologic bases for MP, the evidence for MP use in stroke rehabilitation, and discusses its applications and considerations in patients with stroke-induced motor speech impairments. PMID- 22308051 TI - Depression and anxiety among coronary heart disease patients: can affect dimensions and theory inform diagnostic disorder-based screening? AB - OBJECTIVES: To examine the association between low positive affect, somatic anxiety and general distress with affective disorders, anxious misery, and visceral fear among coronary heart disease patients. PARTICIPANTS: Patients awaiting a coronary revascularization procedure (N = 158; 20.9% female; median age = 65, interquartile range 58-73) underwent structured interview with the Mini International Neuropsychiatric Interview. Patients completed a brief version of the Mood and Anxiety Symptom Questionnaire (i.e., Anxiety Depression Distress Inventory-27) and a measure of Type D personality. RESULTS: Somatic anxiety scores yielded an area under the curve (AUC) = .784 and 75.0% sensitivity and 68.5% specificity in relation to panic disorder. Low positive affect yielded AUC = .811 and 70.4% sensitivity and 77.1% specificity for major depression. General distress yielded AUC = .795 and 75.0% sensitivity and 72.5% specificity for generalized anxiety disorder. No affective dimension was optimally associated with the anxious misery or visceral fear cluster. Trait negative affect was not a suitable screener for any disorder. CONCLUSIONS: The Anxiety Depression Distress Inventory-27 dimensions of low positive affect and somatic anxiety provided optimal detection of depression and panic disorder, respectively, as hypothesized, supporting discriminant validity. PMID- 22308052 TI - Time to get off the fence: the need for definitive international guidance on statistical analysis of ecotoxicity data. AB - The use of the no observed effect concentration (NOEC) and lowest observed effect concentration (LOEC) in ecotoxicology has been consistently criticized for over 30 years. A search of the literature from the past 30 years found 22 articles challenging the validity and/or appropriateness of NOEC/LOEC data compared to only one in defense of such data. Notwithstanding this compelling weight of evidence, the NOEC and LOEC remain commonly published measures of toxicity from ecotoxicological studies. In this article we argue that the major reason for the continued generation and publication of NOEC/LOEC data is that key government and intergovernmental organizations have been "sitting on the fence" on the issue for more than a decade. Although most key environmental quality guideline, toxicity testing, and associated guidance documents have now recognized the limitations of NOEC/LOEC data, to date no such document or standard toxicity test method has formally ceased recommending or providing guidance on the generation of such data. This is a problem because it is these very guidance documents and test methods that regulatory agencies demand be used by industry for regulatory activities, and on which commercial testing facilities attain and maintain their testing accreditation. Consequently, there will be little impetus for change to statistical analysis practices unless changes to the key guidance documents and test methods necessitate it. Although some progress on this has been made (e.g., in Canada, Australia and New Zealand), there needs to be stronger and universal action to ensure NOEC/LOEC data are no longer generated. PMID- 22308053 TI - Valuing the economic benefits of complex interventions: when maximising health is not sufficient. AB - Complex interventions, involving interlinked packages of care, challenge the application of current methods of economic evaluation that focus on measuring only health gain. Complex interventions may be problematic on two levels. The complexity means the intervention may not fit into one of the current appraisal systems, and/or maximising health is not the only objective. This paper discusses the implications of a programme of work that focused on clinical genetics services, as an example of a complex intervention, and aimed to identify the following: the attributes that comprise both health and non-health aspects of benefits and whether it is possible to evaluate such an intervention using current National Institute for Health and Clinical Excellence appraisal processes. Genetic services and tests are a good example of a complex intervention and have broader objectives than just health gain, which may usefully be measured using the concept related to capability, which we have called 'empowerment'. Further methodological work is required to identify the trade-off between non-health (empowerment) and health benefits for other complex interventions. We do not advocate a move away from QALY maximisation but do suggest that there is a need for a more considered approach that can take account of the perceived value for non-health attributes for some complex interventions. PMID- 22308054 TI - The efficacy of licorice root extract in decreasing transaminase activities in non-alcoholic fatty liver disease: a randomized controlled clinical trial. AB - This study was performed to investigate the effects of licorice on non-alcoholic fatty liver disease (NAFLD). In this double blind randomized clinical trial, 66 patients were divided into case and control groups. All patients had elevated liver enzymes and had increased liver echogenicity (lipid accumulation) on sonography. The case group was treated with one capsule containing 2 g aqueous licorice root extract per day for 2 months while the control group was treated in the same manner with a placebo. Weight, body mass index (BMI) and liver transaminase levels were measured for each patient before and after the study. In the case group, the mean alanine aminotransferase (ALT) level decreased from 64.09 to 51.27 IU/mL and the aspartate aminotransferase (AST) level decreased from 58.18 to 49.45 IU/mL, which were statistically significant (p < 0.001 and p < 0.001). But in the control group, a drop in the ALT and AST levels was not statistically significant. The BMI difference before and after the study was not statistically significant in both groups. Despite the significant drop in liver enzymes following administration of licorice root extract, it is recommended that further studies that include histological examination are necessary. PMID- 22308055 TI - Small-molecule stabilization of protein-protein interactions: an underestimated concept in drug discovery? AB - The modulation of protein-protein interactions (PPIs) has been recognized as one of the most challenging tasks in drug discovery. While their systematic development has long been considered as intractable, this view has changed over the last years, with the first drug candidates undergoing clinical studies. To date, the vast majority of PPI modulators are interaction inhibitors. However, in many biological contexts a prolonged lifespan of a PPI might be desirable, calling for the complementary approach of PPI stabilization. In fact, nature offers impressive examples of this concept and some PPI-stabilizing natural products have already found application as important drugs. Moreover, directed small-molecule stabilization has recently been demonstrated. Therefore, it is time to take a closer look at the constructive side of modulating PPIs. PMID- 22308056 TI - EST and transcriptome analysis of cephalochordate amphioxus--past, present and future. AB - The cephalochordates, commonly known as amphioxus or lancelets, are now considered the most basal chordate group, and the studies of these organisms therefore offer important insights into various levels of evolutionary biology. In the past two decades, the investigation of amphioxus developmental biology has provided key knowledge for understanding the basic patterning mechanisms of chordates. Comparative genome studies of vertebrates and amphioxus have uncovered clear evidence supporting the hypothesis of two-round whole-genome duplication thought to have occurred early in vertebrate evolution and have shed light on the evolution of morphological novelties in the complex vertebrate body plan. Complementary to the amphioxus genome-sequencing project, a large collection of expressed sequence tags (ESTs) has been generated for amphioxus in recent years; this valuable collection represents a rich resource for gene discovery, expression profiling and molecular developmental studies in the amphioxus model. Here, we review previous EST analyses and available cDNA resources in amphioxus and discuss their value for use in evolutionary and developmental studies. We also discuss the potential advantages of applying high-throughput, next generation sequencing (NGS) technologies to the field of amphioxus research. PMID- 22308057 TI - Pseudo-heterozygous rearrangement mutation of parkin. AB - BACKGROUND: Mutations in parkin are the most frequent cause of autosomal recessive parkinsonism. Quantitative PCR is used to detect parkin rearrangements. However, the method has an inherent problem-deletion and duplication in the same allelic exon could be determined as normal. To present this misidentification, we report a family with compound heterozygous rearrangements in parkin. METHODS: A patient with early-onset parkinsonism and the parents were investigated by quantitative PCR, haplotype analysis, reverse-transcription PCR, and direct sequencing. RESULTS: A single heterozygous duplication (duplication of exons 6-7) was identified in the patient by quantitative PCR. Detailed analysis of the family revealed the patient carried compound heterozygous of combined deletion (deletion of exons 3-5) and duplication (duplication of exons 3-7). CONCLUSIONS: For correct determination of rearrangement mutation, mutation analysis of the patient as well as other family members and/or break-point analysis of genomic DNA and at the transcript level should be conducted. PMID- 22308058 TI - Studying photoprotective processes in the green alga Chlorella pyrenoidosa using nonlinear laser fluorimetry. AB - We use an advanced fluorescence method of Nonlinear Laser Fluorimetry in combination with Fluorescence Induction and Relaxation technique to study the influence of excess-light conditions on the physiological state of the green alga Chlorella pyrenoidosa. We demonstrate that zeaxanthin-dependent non-photochemical quenching leads to a significant increase in the rate constant of singlet-singlet annihilation of chlorophyll a excited state, which suggests profound conformational changes in the light-harvesting complexes of photosystem II. PMID- 22308059 TI - Family Patterns of Gender Role Attitudes. AB - Study goals were to identify family patterns of gender role attitudes, to examine the conditions under which these patterns emerged, and to assess the implications of gender attitude patterns for family conflict. Participants were mothers, fathers, and first- and second-born adolescents from 358 White, working and middle-class US families. Results of cluster analysis revealed three gender role attitude patterns: egalitarian parents and children, traditional parents and children, and a divergent pattern, with parents more traditional and children more egalitarian. Mixed-model ANOVAs indicated that these family patterns were related to socioeconomic status, parents' time spent in gendered household tasks and with children, and the gender constellation of the sibling dyad. The traditional family group reported the most family conflict. PMID- 22308060 TI - Detection of point-like scatterers using one type of scattered elastic waves. AB - In this paper, we are concerned with the detection of point-like obstacles using elastic waves. We show that one type of waves, either the P or the S scattered waves, is enough for localizing the points. We also show how the use of S incident waves gives better resolution than the P waves. These affirmations are demonstrated by several numerical examples using a MUSIC type algorithm. PMID- 22308061 TI - How word decoding, vocabulary and prior topic knowledge predict reading comprehension. A study of language-minority students in Norwegian fifth grade classrooms. AB - This study examined the contribution of word decoding, first-language (L1) and second-language (L2) vocabulary and prior topic knowledge to L2 reading comprehension. For measuring reading comprehension we employed two different reading tasks: Woodcock Passage Comprehension and a researcher-developed content area reading assignment (the Global Warming Test) consisting of multiple lengthy texts. The sample included 67 language-minority students (native Urdu or native Turkish speakers) from 21 different fifth grade classrooms in Norway. Multiple regression analyses revealed that word decoding and different facets of L2 vocabulary explained most of the variance in Woodcock Passage Comprehension, but a smaller proportion of variance in the Global Warming Test. For the Global Warming Test, prior topic knowledge was the most influential predictor. Furthermore, L2 vocabulary depth appeared to moderate the contribution of prior topic knowledge to the Global Warming Test in this sample of language minority students. PMID- 22308062 TI - QSAR studies on a number of pyrrolidin-2-one antiarrhythmic arylpiperazinyls. AB - The activity of a number of 1-[3-(4-arylpiperazin-1-yl)propyl]pyrrolidin-2-one antiarrhythmic (AA) agents was described using the quantitative structure activity relationship model by applying it to 33 compounds. The molecular descriptors of the AA activity were obtained by quantum chemical calculations combined with molecular modeling calculations. The resulting model explains up to 91% of the variance and it was successfully validated by four tests (LOO, LMO, external test, and Y-scrambling test). Statistical analysis shows that the AA activity of the studied compounds depends mainly on the PCR and JGI4 descriptors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00044-010-9540-x) contains supplementary material, which is available to authorized users. PMID- 22308063 TI - The Stability of Self-Reported Marijuana Use Across Eight Years of the National Longitudinal Survey of Youth. AB - INTRODUCTION: This study examined teen marijuana report stability over eight years. The stability of self-reports refers to the consistency of self-reported use across several years. METHOD: This study used fives waves of data across eight years from the National Longitudinal Survey of Youth. Analyses were conducted to examine the internal or within wave consistency as well as external or across waves consistency for self-reported marijuana use. Further tests were conducted to identify if there were any differences for age, ethnicity and sex for report consistency. RESULTS: Report stability was higher for lifetime use reports than the age of onset reports. Wave-by-wave differences revealed stability remained at acceptable levels in nearly all comparisons at agreement being about 75%. Overall, report agreement was higher for females, older adolescents, and Non-Hispanic/Non-Black youth in bivariate analyses. However, only older chronological age remained consistently significantly associated with better report stability in multiple logistic regression models. Implications regarding misclassification of users for prevention programs and measurement issues are discussed. PMID- 22308064 TI - Mortality Measurement at Advanced Ages: A Study of the Social Security Administration Death Master File. AB - Accurate estimates of mortality at advanced ages are essential to improving forecasts of mortality and the population size of the oldest old age group. However, estimation of hazard rates at extremely old ages poses serious challenges to researchers: (1) The observed mortality deceleration may be at least partially an artifact of mixing different birth cohorts with different mortality (heterogeneity effect); (2) standard assumptions of hazard rate estimates may be invalid when risk of death is extremely high at old ages and (3) ages of very old people may be exaggerated. One way of obtaining estimates of mortality at extreme ages is to pool together international records of persons surviving to extreme ages with subsequent efforts of strict age validation. This approach helps researchers to resolve the third of the above-mentioned problems but does not resolve the first two problems because of inevitable data heterogeneity when data for people belonging to different birth cohorts and countries are pooled together. In this paper we propose an alternative approach, which gives an opportunity to resolve the first two problems by compiling data for more homogeneous single-year birth cohorts with hazard rates measured at narrow (monthly) age intervals. Possible ways of resolving the third problem of hazard rate estimation are elaborated. This approach is based on data from the Social Security Administration Death Master File (DMF). Some birth cohorts covered by DMF could be studied by the method of extinct generations. Availability of month of birth and month of death information provides a unique opportunity to obtain hazard rate estimates for every month of age. Study of several single-year extinct birth cohorts shows that mortality trajectory at advanced ages follows the Gompertz law up to the ages 102-105 years without a noticeable deceleration. Earlier reports of mortality deceleration (deviation of mortality from the Gompertz law) at ages below 100 appear to be artifacts of mixing together several birth cohorts with different mortality levels and using cross-sectional instead of cohort data. Age exaggeration and crude assumptions applied to mortality estimates at advanced ages may also contribute to mortality underestimation at very advanced ages. PMID- 22308065 TI - Icariin promotes extracellular matrix synthesis and gene expression of chondrocytes in vitro. AB - To effectively treat articular cartilage defect with tissue engineering there is an urgent need to develop safe and cheap drugs that can substitute or cooperate with growth factors for chondrogenesis promotion. Here, we demonstrate the chondrogenic effect of icariin, the major pharmacological active constituent of Herb Epimedium (HEP). Rabbit chondrocytes were isolated from articular cartilage and cultured in vitro with different concentrations of icariin. Icariin at concentrations under 1 * 10-5 M showed low cytotoxicity toward chondrocytes, but icariin at 5 * 10-5 M inhibited the proliferation of chondrocytes. Icariin hardly affected the cell morphology with concentrations ranging from 1 * 10-7 M to 5 * 10-5 M. However, the higher concentration of icariin produced more extracellular matrix (ECM) synthesis and expression of chondrogenesis genes of chondrocytes. Indeed, the promotion of icariin on the synthesis of glycosaminoglycans (GAGs) and collagen of chondrocytes, and finally exerting a potent chondrogenic effect, might be due to its ability to up-regulate the expression of aggrecan, collagen II and Sox9 genes and to down-regulate the expression of the collagen I gene of chondrocytes. These preliminary results imply that icariin might be an effective accelerant for chondrogenesis and that icariin-loaded biomaterials might have the potential for cartilage tissue engineering. 1 * 10-5 M may be a suitable concentration of icariin with chondrogenic effect for tissue engineering. PMID- 22308066 TI - Influence of drug distribution and solubility on release from geopolymer pellets- a finite element method study. AB - This study investigates the influence of drug solubility and distribution on its release from inert geopolymer pellets of three different sizes (1.5 * 1.5, 3 * 6, and 6 * 6 mm), having the same geopolymer composition and containing highly potent opioid fentanyl, sumatriptan, theophylline, or saccharin. Scanning electron microscopy, nitrogen sorption, drug solubility, permeation, and release experiments were performed, and estimates of the drug diffusion coefficients and solubilities in the geopolymer matrix were derived with the aid of finite element method (FEM). FEM was further employed to investigate the effect of a nonuniform drug distribution on the drug release profile. When inspecting the release profiles for each drug, it was observed that their solubilities in the geopolymer matrix imposed a much greater influence on the drug release rate than their diffusion coefficients. Concentrating the initial drug load in FEM into nonuniformly distributed drug regions inside the matrix created drug release profiles that more closely resembled experimental data than an FEM-simulated uniform drug distribution did. The presented FEM simulations and visualization of drug release from geopolymers under varying initial and dynamic conditions should open up for more systematic studies of additional factors that influence the drug release profile from porous delivery vehicles. PMID- 22308067 TI - Mortality and morbidity risks and economic behavior. AB - There are theoretical reasons to expect that high risk of mortality or morbidity during young adulthood decreases investment in human capital. However, investigation of this hypothesis is complicated by a variety of empirical challenges, including difficulties in inferring causation due to omitted variables and reverse causation. For example, to compare two groups with substantially different mortality rates, one typically has to use samples from different countries or periods, making it difficult to control for other relevant variables. Reverse causation is important because human capital investment can affect mortality and morbidity. To counter these problems, we collected data on human capital investments, fertility decisions, and other economic choices of people at risk for Huntington's disease. Huntington's disease is a fatal genetic disorder that introduces a large and exogenous risk of early mortality and morbidity. We find a strong negative relation between mortality and morbidity risks and human capital investment. PMID- 22308068 TI - WDR62 missense mutation in a consanguineous family with primary microcephaly. AB - We report on a consanguineous couple with two affected sons who presented with primary microcephaly and moderate to severe intellectual disabilities. A SNP array uncovered two overlapping regions of copy-neutral absence of heterozygosity (AOH) in both sibs. This led to sequencing of WDR62, a gene that codes for a spindle pole protein recently identified as a cause of primary microcephaly. A homozygous missense mutation in WDR62, p.E400K, was found in both boys and segregated with the condition in this family. WDR62 is one of seven genes responsible for autosomal recessive primary microcephaly (MCPH), and appears to be one of the most frequently involved in MCPH following ASPM. Studies of ASPM and WDR62 should perhaps be pursued in all cases of primary microcephaly with or without gross brain malformations. PMID- 22308069 TI - Tetrahydroxynaphthalene reductase: catalytic properties of an enzyme involved in reductive asymmetric naphthol dearomatization. AB - In reduced circumstances: tetrahydroxynaphthalene reductase shows a broad substrate range including alternate phenolic compounds and cyclic ketones. Structural modeling reveals major enzyme-substrate interactions; C-terminal truncation of the enzyme causes an altered substrate preference, in accordance with stabilization of the substrate by the C-terminal carboxylate. This effect allows the identification of a homologous enzyme. PMID- 22308070 TI - Helicobacter pylori Infection and Inflammation: Implication for the Pathophysiology of Diabetes and Coronary Heart Disease in Asian Indians. AB - Asian Indians living in the Indian subcontinent or abroad experience high rate of coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). Asian Indians are also known to suffer from various infections, particularly during their childhood. One such chronic infection is with Helicobacter pylori (H. pylori). Since H. pylori with its specific virulence factor cytotoxin-associated gene A (cagA) has been suggested to be associated with CHD, a role of this H. pylori infection was investigated in the pathogenesis of CHD in Asian Indians living in Bangladesh. H. pylori (CagA) infected subjects with CHD (HP+ve cases, n=21), and without CHD (HP+ve controls, n=20), and non-infected without CHD (HP-ve normal controls, n=21) were included in this study. Thromboxane (TXB), an index of platelet activation, was found to be significantly higher in the HP+ve cases (p=0.05), but not in the HP+ve controls (p=0.88) when compared with HP-ve controls. Analyses of lipid profiles revealed that while triglycerides, total cholesterol and LDL did not show any significant changes, HDL was significantly lower in both the HP+ve cases (p=0.0003) and controls (p=0.005). The mean fasting glucose level in the HP+ve cases was markedly increased (p>0.0001), while it was intermediate in the HP+ve controls, and lowest in the HP-ve controls. HOMA-IR values, a measure of insulin resistance, did not reflect any substantial differences between the HP+ve and HP-ve controls, but they were highly significantly different between the HP+ve cases and HP-ve controls. HOMA-B, indicating insulin secretory dysfunction (ISD), was significantly higher in both the HP+ve groups when compared with the normal controls. The data indicate that H. pylori infection is associated with impaired insulin secretion, and that a component of insulin resistance that occurs independent of H. pylori can then lead to a worsening of glucose tolerance and the development of CHD. This is the first demonstration to our knowledge that H. pylori (CagA) infection is associated with insulin secretory dysfunction in human subjects. Since many Asian Indians contract various other chronic and acute infections, it is important to investigate the role of H. pylori and other infectious agents in the pathogenesis of T2DM and CHD. PMID- 22308071 TI - Quantitative discrimination of NPC cell lines using optical coherence tomography. AB - We tried to explore the intrinsic differences in the optical properties of the four representative NPC cell lines on the models of radiobiology and metastasis by OCT. The scattering coefficients and anisotropies were extracted by fitting the average a-scan attenuation curves based on the multiple scatter effect. The values of scattering coefficients and anisotropy factors were 5.21 +/- 0.11, 5.30 +/- 0.09, 5.92 +/- 0.21, 6.97 +/- 0.22, and 0.892 +/- 0.009, 0.886 +/- 0.006, 0.884 +/- 0.009, 0.86 +/- 0.01 for CNE1, CNE2, 5-8F and 6-10B pellets (p < 0.05, P = 0.07 for CNE1 and CNE2), respectively. The results showed that the radiobiology and metastasis cell's model could be distinguished obviously; which implied that the corresponding types of NPC tissue might be potentially differentiated by OCT. PMID- 22308072 TI - A new method of spermatic cord mobilization in herniorrhaphy. AB - Spermatic cord mobilization is a routine part of inguinal hernia repair, but the method of cord mobilization varies among surgeons. This study establishes an anatomic plane for spermatic cord mobilization. We studied the anatomy of the superficial cremasteric fascia in 105 male patients during herniorrhaphy for primary inguinal hernias. The mean patient age was 44.8 (18-71) years and mean body mass index was 24.1 kg/m(2) (21.5-27.1 kg/m(2)). The two layers of the superficial cremasteric fascia between the spermatic cord and the inguinal falx were incised to mobilize the cord. We found that spermatic cord mobilization during herniorrhaphy can be easily approached through an anatomic plane between the spermatic cord and the conjoined tendon with subsequent division of the superficial cremasteric fascia. None of the patients experienced any hemorrhage or nerve injury during cord mobilization. We found this method to be both safe and easy to learn. PMID- 22308073 TI - Measuring the microbiome: perspectives on advances in DNA-based techniques for exploring microbial life. AB - This article reviews recent advances in 'microbiome studies': molecular, statistical and graphical techniques to explore and quantify how microbial organisms affect our environments and ourselves given recent increases in sequencing technology. Microbiome studies are moving beyond mere inventories of specific ecosystems to quantifications of community diversity and descriptions of their ecological function. We review the last 24 months of progress in this sort of research, and anticipate where the next 2 years will take us. We hope that bioinformaticians will find this a helpful springboard for new collaborations with microbiologists. PMID- 22308074 TI - The Quantum Workings of the Rotating 64-Grid Genetic Code. AB - In this article, the pattern learned from the classic or conventional rotating circular genetic code is transferred to a 64-grid model. In this non-static representation, the codons for the same amino acid within each quadrant could be exchanged, wobbling or rotating in a quantic way similar to the electrons within an atomic orbit. Represented in this 64-grid format are the three rules of variation encompassing 4, 2, or 1 quadrant, respectively: 1) same position in four quadrants for the essential hydrophobic amino acids that have U at the center, 2) same or contiguous position for the same or related amino acids in two quadrants, and 3) equivalent amino acids within one quadrant. Also represented is the mathematical balance of the odd and even codons, and the most used codons per amino acid in humans compared to one diametrically opposed organism: the plant Arabidopsis thaliana, a comparison that depicts the difference in third nucleotide preferences: a C/U exchange for 11 amino acids, a G/A exchange for 2 amino acids, and G/U or C/A exchanges for one amino acid, respectively; by studying these codon usage preferences per amino acid we present our two hypotheses: 1) A slower translation in vertebrates and 2) a faster translation in invertebrates, possibly due to the aqueous environments where they live. These codon usage preferences may also be able to determine genomic compatibility by comparing individual mRNAs and their functional third dimensional structure, transport and translation within cells and organisms. These observations are aimed to the design of bioinformatics computational tools to compare human genomes and to determine the exchange between compatible codons and amino acids, to preserve and/or to bring back extinct biodiversity, and for the early detection of incompatible changes that lead to genetic diseases. PMID- 22308075 TI - A coherent geostatistical approach for combining choropleth map and field data in the spatial interpolation of soil properties. AB - Information available for mapping continuous soil attributes often includes point field data and choropleth maps (e.g. soil or geological maps) that model the spatial distribution of soil attributes as the juxtaposition of polygons (areas) with constant values. This paper presents two approaches to incorporate both point and areal data in the spatial interpolation of continuous soil attributes. In the first instance, area-to-point kriging is used to map the variability within soil units while ensuring the coherence of the prediction so that the average of disaggregated estimates is equal to the original areal datum. The resulting estimates are then used as local means in residual kriging. The second approach proceeds in one step and capitalizes on: 1) a general formulation of kriging that allows the combination of both point and areal data through the use of area-to-area, area-to-point, and point-to-point covariances in the kriging system, 2) the availability of GIS to discretize polygons of irregular shape and size, and 3) knowledge of the point-support variogram model that can be inferred directly from point measurements, thereby eliminating the need for deconvolution procedures. The two approaches are illustrated using the geological map and heavy metal concentrations recorded in the topsoil of the Swiss Jura. Sensitivity analysis indicates that the new procedures improve prediction over ordinary kriging and traditional residual kriging based on the assumption that the local mean is constant within each mapping unit. PMID- 22308076 TI - Effect of grapefruit juice and ritonavir on pharmacokinetics of lopinavir in Wistar rats. AB - Lopinavir (LPV), a newer HIV protease inhibitor, has poor bioavailability being a substrate of both cytochrome P450 3A enzyme system (CYP3A) and permeability glycoprotein (P-gp). Ritonavir (RTV) is a known inhibitor of both P-gp and CYP3A and is co-administered with LPV in anti-HIV therapy. Grapefruit juice (GFJ) is known to inhibit CYP3A and has conflicting effects, ranging from activation to inhibition, on P-gp. In this research work, the effects of GFJ and RTV on the pharmacokinetics of LPV were compared in rats. A mechanistic evaluation was undertaken using various in vitro and ex vivo studies to support the in vivo pharmacokinetic data. The plasma levels of LPV were found to increase significantly upon co-administration with GFJ in single dose as well as multidose pretreatment studies. Similar, but marginally higher, results were observed upon co-administration of LPV with RTV. No significant change in t(max) was observed in the various treatment groups. The apparent permeability of LPV in the ileum increased significantly after the pre-incubation with GFJ and RTV compared with no pre-incubation. The GFJ and RTV showed a significant and similar inhibitory effect on rat intestinal microsomes in the metabolism of LPV. The GFJ was equally effective as RTV in increasing the bioavailability of LPV. PMID- 22308077 TI - Enantioselective iridium-catalyzed hydrogenation of beta,gamma-unsaturated carboxylic acids: an efficient approach to chiral 4-alkyl-4-aryl butanoic acids. AB - Chiral acids: a highly enantioselective iridium-catalyzed hydrogenation of beta,gamma-unsaturated carboxylic acids is developed for the preparation of chiral 4-alkyl-4-aryl butanoic acids. PMID- 22308078 TI - Implications for genotype-phenotype predictions in Townes-Brocks syndrome: case report of a novel SALL1 deletion and review of the literature. AB - Townes-Brocks syndrome (TBS) is a well-described genetic syndrome characterized by anal, ear, and thumb anomalies and variable expressivity. Over 60 nonsense and frameshift mutations have been identified in SALL1, the zinc finger transcription factor causing TBS, and are proposed to cause disease via a dominant negative mechanism. In contrast, only four deletions have been described, with mild phenotypes reported as a result of haploinsufficiency. We report on a family with features of TBS in whom a novel 149 kb deletion spanning the SALL1 gene was identified by high resolution cytogenetics SNP microarray. We review the available genotype-phenotype information for all known truncating mutations and deletions. Taken together, they do not support the correlation of SALL1 deletions with a milder TBS phenotype and highlight a need for more robust clinical phenotyping combined with investigation of mutational mechanism. PMID- 22308079 TI - Embarking on large-scale qualitative research: reaping the benefits of mixed methods in studying youth, clubs and drugs. AB - Qualitative research is often conceptualized as inherently small-scale research, primarily conducted by a lone researcher enmeshed in extensive and long-term fieldwork or involving in-depth interviews with a small sample of 20 to 30 participants. In the study of illicit drugs, traditionally this has often been in the form of ethnographies of drug-using subcultures. Such small-scale projects have produced important interpretive scholarship that focuses on the culture and meaning of drug use in situated, embodied contexts. Larger-scale projects are often assumed to be solely the domain of quantitative researchers, using formalistic survey methods and descriptive or explanatory models.In this paper, however, we will discuss qualitative research done on a comparatively larger scale-with in-depth qualitative interviews with hundreds of young drug users. Although this work incorporates some quantitative elements into the design, data collection, and analysis, the qualitative dimension and approach has nevertheless remained central. Larger-scale qualitative research shares some of the challenges and promises of smaller-scale qualitative work including understanding drug consumption from an emic perspective, locating hard-to-reach populations, developing rapport with respondents, generating thick descriptions and a rich analysis, and examining the wider socio-cultural context as a central feature. However, there are additional challenges specific to the scale of qualitative research, which include data management, data overload and problems of handling large-scale data sets, time constraints in coding and analyzing data, and personnel issues including training, organizing and mentoring large research teams. Yet large samples can prove to be essential for enabling researchers to conduct comparative research, whether that be cross-national research within a wider European perspective undertaken by different teams or cross-cultural research looking at internal divisions and differences within diverse communities and cultures. PMID- 22308080 TI - Changing coronary sinus activation during catheter ablation of isthmus-dependent right atrial flutter: what is the mechanism? AB - A 69-year-old woman was referred for cavotricuspid isthmus ablation due to typical isthmus-dependent right atrial flutter. During ablation, intracardiac activation sequence in coronary sinus (CS) changed without altering the cycle length or the P-wave morphology. This suggests that interatrial connection via CS was blocked and left atrium (LA) was activated from Bachmann's bundle or/and connections between fossa ovalis and LA. PMID- 22308081 TI - Sudden cardiac death and implantable cardioverter defibrillators: two modern epidemics? AB - Critical analysis of the existing evidence indicates that: In patients with documented sustained ventricular arrhythmias and/or cardiac arrest, implantable cardioverter defibrillators (ICDs) confer a survival benefit. In several clinical settings this is rather transient, and might be lost when modern medical therapy including beta-blockers is implemented. In patients without sustained ventricular arrhythmias or cardiac arrest, ICDs confer a significant survival benefit only in high-risk patients with ischaemic cardiomyopathy and left ventricular ejection fraction of <= 35% due to a remote myocardial infarction. Left ventricular ejection fraction alone is rather unlikely to be sufficient for effective sudden cardiac death risk prediction, due to low sensitivity and specificity. The benefits of ICDs in the elderly as well as in women are not established. With current prices, ICDs are probably cost-effective only when used in high-risk patients without associated comorbidities that limit the life expectancy to <10 years. Recommendations by current guidelines may result in unnecessary overuse of ICD. PMID- 22308082 TI - The J wave and fragmented QRS complexes in inferior leads associated with sudden cardiac death in patients with chronic heart failure. AB - AIMS: To investigate the relationship between electrocardiogram (ECG) parameters [J wave, fragmented QRS (fQRS), QTc, the peak-to-end interval of T wave (Tp-Te)], and sudden cardiac death (SCD) in chronic heart failure (CHF). METHODS AND RESULTS: The ECGs of 1570 CHF patients, 572 cases with dilated cardiomyopathy (DCM) and 998 cases with ischaemic cardiomyopathy (ICM) were analysed with the endpoint being an SCD or non-SCD (NSCD). During a median follow-up period of 36 months (0.40-65 months), 438 (27.89%) patients died, of which 158 (35.84%) were SCD. Overall, the occurrence of J wave, fQRS, and long Tp-Te were greater in SCD patients than that of NSCD patients (all P< 0.01). For DCM cases, more SCD patients had J waves observed in the inferior leads than that in the NSCD group (26.78 vs. 13.07%, P<0.001). However, ICM cases with SCD did have more fQRS in the inferior leads than that with NSCD (42.16 vs. 26.67%, P= 0.01). After adjusting for other risk factors, Cox regression analysis revealed that presence of J wave or fQRS in the inferior leads predicted a higher risk for SCD in DCM [hazard ratio (HR), 4.095; 95% confidence interval (CI), 2.132-7.863] and ICM (HR, 2.714; 95% CI, 1.809-4.072) patients. A left ventricular ejection fraction <= 30% also predicted SCD and NSCD in DCM and ICM patients. In contrast, the predictive value of QTc and Tp-Te for SCD was not significant. CONCLUSIONS: Presence of J wave or fQRS in the inferior leads predicted higher risk of SCD in DCM and ICM patients and might serve as independent predictors for SCD in patients with CHF. PMID- 22308083 TI - Measures of spatiotemporal organization differentiate persistent from long standing atrial fibrillation. AB - AIMS: This study presents an automatic diagnostic method for the discrimination between persistent and long-standing atrial fibrillation (AF) based on the surface electrocardiogram (ECG). METHODS AND RESULTS: Standard 12-lead ECG recordings were acquired in 53 patients with either persistent (N= 20) or long standing AF (N= 33), the latter including both long-standing persistent and permanent AF. A combined frequency analysis of multiple ECG leads followed by the computation of standard complexity measures provided a method for the quantification of spatiotemporal AF organization. All possible pairs of precordial ECG leads were analysed by this method and resulting organization measures were used for automatic classification of persistent and long-standing AF signals. Correct classification rates of 84.9% were obtained, with a predictive value for long-standing AF of 93.1%. Spatiotemporal organization as measured in lateral precordial leads V5 and V6 was shown to be significantly lower during long-standing AF than persistent AF, suggesting that time-related alterations in left atrial electrical activity can be detected in the ECG. CONCLUSION: Accurate discrimination between persistent and long-standing AF based on standard surface recordings was demonstrated. This information could contribute to optimize the management of sustained AF, permitting appropriate therapeutic decisions and thereby providing substantial clinical cost savings. PMID- 22308084 TI - Clinical implication of right ventricular to left ventricular interlead sensed electrical delay in cardiac resynchronization therapy. AB - AIMS: To evaluate the clinical implication of right ventricular (RV) to left ventricular (LV) interlead sensed electrical delay (RV-LVs) and the relation to ventricular lead position in cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Eighty-five consecutive CRT patients (mean age 66 +/- 11 years) received LV lead prospectively targeted to the latest mechanical activated segment (concordant), assessed by two-dimensional speckle tracking radial strain (ST-RS) echocardiography. The RV lead was randomized to RV apex (n= 43) or RV high posterior septum (n= 42). Right ventricular to left ventricular interlead sensed electrical delay was obtained during the CRT implant procedure. Intraventricular dyssynchrony was evaluated by ST-RS echocardiography. Interventricular mechanical delay (IVMD) was measured by using pulse-wave Doppler. Separated by the median RV LVs (82 ms), a long RV-LVs demonstrated more LV end-systolic volume (LVESV) reduction than a short RV-LVs (-27 +/- 20 vs. -16 +/- 22%; P= 0.02), 6 months after CRT (6FU). Right ventricular to left ventricular interlead sensed electrical delay correlated to IVMD (r = 0.50; P< 0.001) and intraventricular dyssynchrony (r = 0.25; P= 0.02) at baseline. Concordant LV leads (n= 61) demonstrated superior reduction of LVESV (P= 0.005) 6 months after CRT; however, both RV lead positions had similar effects. Right ventricular to left ventricular interlead sensed electrical delay was irrespective to LV lead concordance and RV lead position (P= ns). Independent predictors to reverse remodelling (reduction of LVESV >= 15%) at 6FU were concordant LV lead (odds ratio, 3.210; P= 0.029) and IVMD (odds ratio, 1.028; P= 0.026). CONCLUSION: Right ventricular to left ventricular interlead sensed electrical delay was not predictive to LV reverse remodelling affected by CRT at 6FU. Concordant LV leads demonstrated superior LV reverse remodelling at 6FU. Right ventricular to left ventricular interlead sensed electrical delay was irrespective of ventricular lead position and might be insufficient to target optimal LV lead position in CRT. TRIAL REGISTRATION: http://clinicaltrials.gov. Unique identifier: NCT01035489. PMID- 22308085 TI - Increased intracardiac vascular endothelial growth factor levels in patients with paroxysmal, but not persistent atrial fibrillation. AB - AIMS: Although inflammation appears to play a pivotal role in the pathophysiology of atrial fibrillation (AF), the source of inflammation is unknown. We hypothesized that multilevel measurement of several inflammatory proteins in AF patients would help assess the extent and the source of inflammation. METHODS AND RESULTS: Thirty-nine patients with paroxysmal AF, 33 with persistent AF, and 9 control patients with Wolff-Parkinson-White syndrome were enrolled. Peripheral, left atrial, coronary sinus, and pulmonary vein blood samples were obtained during catheterization. Serum levels of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), soluble intercellular adhesion molecule 1 (sICAM 1), and transforming growth factor-beta1 (TGF-beta1) were measured at the four sampled sites. Interleukin-8, sICAM-1, and TGF-beta1 levels did not differ among groups at any of the sampled sites. Peripheral VEGF levels were higher in both paroxysmal and persistent AF patients than in controls (P <= 0.03). Left atrial VEGF levels were higher in paroxysmal AF (P = 0.05), but not in persistent AF (P = 0.32), compared with controls. Coronary sinus and pulmonary vein VEGF levels did not differ significantly among groups. CONCLUSIONS: Low levels of several inflammatory markers in both paroxysmal and persistent AF patients suggest that the inflammatory process is of low grade, if present. In the context of normal pulmonary vein VEGF levels, the heart itself is the most likely source of high left atrial VEGF levels in paroxysmal AF patients; however, this disorder appears to be a transient event in the natural history of AF. PMID- 22308086 TI - Improved screening for silent atrial fibrillation after ischaemic stroke. AB - OBJECTIVES: To what extent silent paroxysmal atrial fibrillation (AF) is present in ischaemic stroke patients has not been established. We hypothesized that brief intermittent long-term electrocardiogram (ECG) recordings at regular time intervals are more effective than short-term continuous ECG monitoring in detecting silent AF episodes. METHODS AND RESULTS: Consecutive patients who had suffered an ischaemic stroke/transient ischaemic attack (TIA) and were without known AF underwent a 24 h continuous ECG recording and performed 10 s rhythm registrations using a hand-held ECG recorder twice daily for 30 days and when arrhythmia symptoms occured. Two hundred and forty-nine stroke patients were included. Mean National Institute of Health Stroke Scale (NIHSS) score was 0.9 (0 10). In total, 17 patients were diagnosed with AF. One hundred and eight AF episodes were diagnosed in 15 patients using intermittent recording, out of which 22% where unscheduled symptom triggered episodes. In three patients AF was diagnosed with both methods and in two patients AF was detected exclusively with 24 h Holter monitoring. A significant difference in favour of the hand-held ECG was shown between the two methods (P = 0.013). The total prevalence of AF was 6.8% and increased to 11.8% in patients >=75 years. No AF was found in patients <65 years. CONCLUSIONS: Prolonged brief intermittent arrhythmia screening substantially improves the detection of silent paroxysmal AF in patients with a recent ischaemic stroke/TIA, and thus facilitates the detection of patients who should receive oral anticoagulant treatment. PMID- 22308087 TI - Telemonitoring with implantable electronic devices in young patients with congenital heart diseases. AB - AIMS: In paediatric patients with a pacemaker (PM) or an implantable cardioverter defibrillator (ICD) device, interrogation during in-clinic visits is usually required to obtain information on arrhythmias or system failures. An automated telemonitoring system tracking patient- and system-related parameters provides this information on a daily basis and might assist patient management. METHODS AND RESULTS: This retrospective analysis evaluates telemetric data obtained from 48 devices implanted in 45 patients (median age, 12.4 years; range, 5 weeks to 37.6 years) using an automated system [Home Monitoring (HM)] over the last 5 years. Regular transmissions were received on 72% of all days. The event messages and monitoring data of 34 (71%) devices induced system revisions, electrophysiological studies including ablation, programming changes, medication changes, and alterations in sporting activity. Approximately 47% of event messages and 50% of emergency messages arrived within 4 weeks of implantation or latest outpatient visit; 113 (17%) emergency messages reported acute changes in lead parameters or tachycardia, which required medical intervention. In four ICD patients, delivered shocks were unreported and only detected by HM. CONCLUSIONS: An automated telemonitoring system reporting patient- and system-related parameters, generated within the patient's home surrounding, can improve the safety and quality of PM and ICD therapy, especially in children, by allowing early detection of system failure and changes in arrhythmic events. PMID- 22308088 TI - Transseptal catheterization: a matter of technology, training, or both? PMID- 22308089 TI - Prevalence of electrocardiographic abnormalities in an unselected young male multi-ethnic South-East Asian population undergoing pre-participation cardiovascular screening: results of the Singapore Armed Forces Electrocardiogram and Echocardiogram screening protocol. AB - AIMS: Resting 12-lead electrocardiograms (ECGs) have been employed in the pre participation evaluation of young asymptomatic subjects to detect pre-existing heart diseases. Although the incorporation of routine ECG in pre-participation screening remains controversial, there is increasing evidence that cardiomyopathies and ion channelopathies have ECG changes as the initial manifestation. The causes of sudden cardiac death in young people show significant geographical variation. We aim to determine the prevalence and spectrum of ECG abnormalities in a young male South-East Asian population. METHODS AND RESULTS: The Singapore Armed Forces Electrocardiogram and Echocardiogram (SAFE) protocol is an ECG-based pre-participation cardiac screening programme modelled after the Italian system. From October 2008 to May 2009, a total of 18 476 young male conscripts (mean age 19.5 years old, range 16 27) underwent mandatory pre-enlistment medical screening at a single medical facility. Subjects with abnormal ECG findings were classified into two groups: Group A had ECG changes that fulfilled a pre-specified checklist to screen for hypertrophic cardiomyopathy and were referred for transthoracic echocardiogram; Group B had other ECG abnormalities [such as Brugada pattern, Wolff-Parkinson White (WPW) pattern, long QTc] and were referred for secondary screening at a tertiary institution. Of the 18 476 subjects screened, 7.0% (n= 1285) had ECG abnormalities. Of note, 19 (0.10%) had Brugada pattern, 25 (0.14%) had WPW pattern, and 31 (0.17%) had prolonged QT interval on ECG. The prevalence of ECG abnormalities was significantly higher in Chinese than in South Asians (7.2 vs. 5.7%, P= 0.003). CONCLUSION: The prevalence of ECG abnormalities in a young, South-East Asian male population was 7.0%. There were significant ethnic differences, with ECG abnormalities more prevalent in Chinese than in South Asians (7.2 vs. 5.7%, P= 0.003). The inclusion of universal ECG, in addition to history and physical examination, may increase the sensitivity of a cardiovascular screening programme. Knowledge of the spectrum and prevalence of ECG abnormalities and disease conditions would be pivotal in designing customized screening programmes. PMID- 22308090 TI - Direction-dependent conduction abnormalities in the chronically stretched atria. AB - AIMS: There is increasing evidence of the role direction-dependent conduction plays in the arrhythmogenic interaction between ectopic triggers and abnormal atrial substrates. We thus sought to characterize direction-dependent conduction in chronically stretched atria. METHODS AND RESULTS: Twenty-four patients with chronic atrial stretch due to mitral stenosis and 24 reference patients with left sided accessory pathways were studied. Multipolar catheters placed at the lateral right atrium, crista terminalis, and coronary sinus (CS) characterized direction dependent conduction along linear catheters and across the crista terminalis. Bi atrial electroanatomic maps were created in both sinus rhythm and an alternative wavefront direction by pacing from the distal CS. This allowed an assessment of conduction velocities, electrogram, and voltage characteristics during wavefronts propagating in different directions. While differing wavefront directions caused changes in both chronic atrial stretch and reference patients (P< 0.001 for all), these direction-dependent changes were greater in chronic atrial stretch compared with reference patients, who exhibited greater slowing in conduction velocities (P= 0.09), prolongation of bi-atrial activation time (P= 0.04), increase in number (P< 0.001) and length (P< 0.001) of lines of conduction block, increase in fractionated electrograms (P< 0.001), and decrease in voltage (P= 0.08) during left-to-right compared with right-to-left atrial activation. These direction dependent changes were associated with a greater propensity for chronically stretched atria to develop atrial fibrillation (P= 0.02). CONCLUSIONS: Atrial remodelling in chronic atrial stretch exacerbates physiological direction dependent conduction characteristics. Our data suggest that the greater direction dependent conduction seen in patients with chronic atrial stretch may promote arrhythmogenesis due to ectopic triggers from the left atrium. PMID- 22308091 TI - 'Born' with a 'dead'-end-tract resulting in arrhythmias in the aorto-mitral continuity: coincidence, causation, and 'commensuration'. PMID- 22308092 TI - Computer tomographic evaluation of talar edge configuration for osteochondral graft transplantation. AB - To successfully surgically reconstruct osteochondral lesions of the talus, the exact three-dimensional (3D) configuration of the upper articular surface of the talus has to be respected. We assessed the talar geometry by measuring the coronal and sagittal talar edge radius and the frontal talar profile in multiplanar reconstructions of computer tomographic (CT) studies of 79 patients (83 feet) with a healthy ankle joint. An image visualization software designated for coordinate measurement was used to perform the measurement. In the coronal plane, the mean lateral talar edge radius was 4.0 mm and the medial 4.5 mm. In the sagittal planes the mean lateral talar edge radius was 20.3 mm, the radius of the sulcus 20.7 mm and the medial talar edge radius 20.4 mm. The talus showed a concave shape in coronal cuts. These results show a significant difference between medial and lateral talar edge configuration in coronal planes. The measurements of the lateral and medial sagittal radius and the mid-sagittal radius in the sulcus tali show no statistically significant difference. The depth of the talar sulcus shows no correlation to age or sex. Different sizes of custom made tissue-engineered grafts according to the location of the osteochondral lesion at the talus are needed for exact surgical reconstruction of the anatomy. Osteochondral lesions are three dimensional; therefore, a 3D preoperative planning tool by CT scan or MRI is mandatory. PMID- 22308093 TI - In vivo measurements of diffuse reflectance and time-resolved autofluorescence emission spectra of basal cell carcinomas. AB - We present a clinical investigation of diffuse reflectance and time-resolved autofluorescence spectra of skin cancer with an emphasis on basal cell carcinoma. A total of 25 patients were measured using a compact steady-state diffuse reflectance/fluorescence spectrometer and a fibre-optic-coupled multispectral time-resolved spectrofluorometer. Measurements were performed in vivo prior to surgical excision of the investigated region. Singular value decomposition was used to reduce the dimensionality of steady state diffuse reflectance and fluorescence spectra. Linear discriminant analysis was then applied to the measurements of basal cell carcinomas (BCCs) and used to predict the tissue disease state with a leave-one-out methodology. This approach was able to correctly diagnose 87% of the BCCs. With 445 nm excitation a decrease in the spectrally averaged fluorescence lifetime was observed between normal tissue and BCC lesions with a mean value of 886 ps. Furthermore, the fluorescence lifetime for BCCs was lower than that of the surrounding healthy tissue in all cases and statistical analysis of the data revealed that this decrease was significant (p = 0.002). PMID- 22308094 TI - Early detection of metabolic changes using microdialysis during and after experimental kidney transplantation in a porcine model. AB - BACKGROUND: Microdialysis (MD) can detect organ-related metabolic changes before they become measurable in plasma through the biochemical parameters. This study aims to evaluate the early detection of metabolic changes during experimental kidney transplantation (KTx). MATERIAL AND METHODS: During preparation of 8 donor kidneys, one MD catheter was inserted in the renal cortex and samples were collected. After a 6-hour cold ischemia time (CIT), kidneys were implanted in the 8 recipient pigs. Throughout the warm ischemia time (WIT) and after reperfusion, kidneys were monitored. The interstitial glucose, lactate, pyruvate, glutamate, and glycerol concentrations were evaluated. RESULTS: A significant decline in glucose level was observed at the end of CIT. The lactate level was reduced to the minimum point of 0.35 +/- 0.08 mmol/L in CIT. After reperfusion, lactate values raised significantly. During the WIT, the pyruvate level increased, continued until the end of the WIT. For glutamate, a steady increase was noted during explantation, CIT, WIT, and early reperfusion phases. The increase of glycerol value continued in the early postreperfusion, which was then followed by a sharp decline. CONCLUSION: MD is a fast and simple minimally invasive method for measurement of metabolic substrates in renal parenchyma during KTx. MD offers the option of detecting minor changes of interstitial glucose, lactate, pyruvate, glutamate, and glycerol in every stage of KTx. Through the use of MD, metabolic changes can be continuously monitored during the entire procedure of KTx. PMID- 22308095 TI - Agricultural Pesticide Management in Thailand: Situation and Population Health Risk. AB - As an agricultural country and one of the world's major food exporters, Thailand relies heavily on the use of pesticides to protect crops and increase yields. During the past decade, the Kingdom of Thailand has experienced an approximate four-fold increase in pesticide use. This increase presents a challenge for the Royal Thai Government in effectively managing and controlling pesticide use based upon the current policies and legal infrastructure. We have reviewed several key components for managing agricultural pesticides in Thailand. One of the main obstacles to effective pesticide regulation in Thailand is the lack of a consolidated, uniform system designed specifically for pesticide management. This deficit has weakened the enforcement of existing regulations, resulting in misuse/overuse of pesticides, and consequently, increased environmental contamination and human exposure. This article provides a systematic review of how agricultural pesticides are regulated in Thailand. In addition, we provide our perspectives on the current state of pesticide management, the potential health effects of widespread, largely uncontrolled use of pesticides on the Thai people and ways to improve pesticide management in Thailand. PMID- 22308096 TI - xQTL workbench: a scalable web environment for multi-level QTL analysis. AB - SUMMARY: xQTL workbench is a scalable web platform for the mapping of quantitative trait loci (QTLs) at multiple levels: for example gene expression (eQTL), protein abundance (pQTL), metabolite abundance (mQTL) and phenotype (phQTL) data. Popular QTL mapping methods for model organism and human populations are accessible via the web user interface. Large calculations scale easily on to multi-core computers, clusters and Cloud. All data involved can be uploaded and queried online: markers, genotypes, microarrays, NGS, LC-MS, GC-MS, NMR, etc. When new data types come available, xQTL workbench is quickly customized using the Molgenis software generator. AVAILABILITY: xQTL workbench runs on all common platforms, including Linux, Mac OS X and Windows. An online demo system, installation guide, tutorials, software and source code are available under the LGPL3 license from http://www.xqtl.org. CONTACT: m.a.swertz@rug.nl. PMID- 22308097 TI - The Impact of Family Communication Patterns on Hospice Family Caregivers: A New Typology. PMID- 22308098 TI - Factors influencing survival in patients undergoing palliative bypass for pancreatic adenocarcinoma. AB - PURPOSE: The purpose of this study is to identify factors predictive of early mortality following palliative bypass in patients with previously unsuspected advanced pancreatic adenocarcinoma to provide a basis for the selection of appropriate therapies. METHODS: All patients with pancreatic adenocarcinoma who underwent a bypass procedure at our institution between 9/30/1994 and 1/31/2006 were reviewed. Patients with peri-operative mortality were excluded from the analysis. Univariate analysis was performed on peri-operative data to identify factors associated with early mortality (death within 6 months of surgery). Patients having multiple risk factors were assigned an overall prognostic score based on the sum of these factors. RESULTS: Of the 397 patients with pancreatic adenocarcinoma analyzed, four factors were found to predict early mortality following palliative bypass: Presence of distant metastatic disease (HR 2.59, P < 0.0001), poor tumor differentiation (HR 1.71, P = 0.009), severe pre-operative nausea and vomiting (HR 1.48, P = 0.013), and lack of previous placement of a biliary stent (HR 1.36, P = 0.048). Patients with a prognostic score of 0 were significantly more likely to survive past 6 months than patients with a prognostic score of 1 (HR 2.71, P < 0.0001), 2 (HR 3.70, P < 0.0001), or >=3 (HR 5.63, P < 0.0001). CONCLUSIONS: In a cohort of patients undergoing a palliative bypass procedure, specific peri-operative factors can be used to identify patients who are at risk of early mortality. These factors may be helpful in selecting appropriate interventions for this group of patients. PMID- 22308099 TI - Bioactive compounds from Carissa spinarum. AB - In our continuing efforts to find new antiherpetic agents from plants, an extract prepared from the stems of Carissa spinarum L. was found to possess appreciable activity against herpes simplex viruses (HSV I and II). A chemical study of this plant was then initiated, and this led to the isolation of 12 compounds, including a coumarin, two cardiac glycosides and nine lignans. These isolated compounds were evaluated for several biological activities, including antiherpetic, cytotoxic, antioxidant and antibacterial effects. The cardiac glycoside evomonoside was found to be the only antiherpetic principle, showing moderate activity against herpes simplex virus types I and II in the inactivation method. The lignans (-)-carinol, (-)-carissanol and (-)-nortrachelogenin exhibited cytotoxicity against breast (MCF7) and lung (A549) cancer cells. Moderate anti-DPPH free radical activity was observed for all the lignans. None of the isolates showed antibacterial activity. PMID- 22308100 TI - Mesoporous materials in peptidome analysis. PMID- 22308101 TI - Transcriptomic alterations in human prostate cancer cell LNCaP tumor xenograft modulated by dietary phenethyl isothiocyanate. AB - Temporal growth of tumor xenografts in mice on a control diet was compared to mice supplemented daily with 3 umol/g of the cancer preventive compound phenethyl isothiocyanate. Phenethyl isothiocyanate decreased the rate of tumor growth. The effects of phenethyl isothiocyanate on tumor growth were examined by RNAseq to elucidate molecular changes that may contribute to tumor growth suppression. Bio informatic analysis of differentially expressed genes identified changes in inflammation and extracellular matrix pathways that were modulated by treatment with phenethyl isothiocyanate. Specific gene expression changes in these pathways included up-regulation of insulin-like growth factor binding protein 3, fibronectin, thyroxine degradation enzyme, and down regulation of integrin beta 6. In addition, feeding phenethyl isothiocyanate induced alternative splicing of gene variants. This study represents the first use of RNAseq to analyze tumors from animals consuming dietary phenethyl isothiocyanate and to identify potential molecular signatures that may explain the cancer protective effect of this compound. PMID- 22308102 TI - The globally distributed genus Alexandrium: multifaceted roles in marine ecosystems and impacts on human health. AB - The dinoflagellate genus Alexandrium is one of the major harmful algal bloom (HAB) genera with respect to the diversity, magnitude and consequences of blooms. The ability of Alexandrium to colonize multiple habitats and to persist over large regions through time is testimony to the adaptability and resilience of this group of species. Three different families of toxins, as well as an as yet incompletely characterized suite of allelochemicals are produced among Alexandrium species. Nutritional strategies are equally diverse, including the ability to utilize a range of inorganic and organic nutrient sources, and feeding by ingestion of other organisms. Many Alexandrium species have complex life histories that include sexuality and often, but not always, cyst formation, which is characteristic of a meroplanktonic life strategy and offers considerable ecological advantages. Due to the public health and ecosystem impacts of Alexandrium blooms, the genus has been extensively studied, and there exists a broad knowledge base that ranges from taxonomy and phylogeny through genomics and toxin biosynthesis to bloom dynamics and modeling. Here we present a review of the genus Alexandrium, focusing on the major toxic and otherwise harmful species. PMID- 22308103 TI - Highly proton-selective biopolymer layer-coated ion-exchange membrane for direct methanol fuel cells. PMID- 22308104 TI - Abundance- and Activity-Based Proteomics in Platelet Biology. AB - Human platelets are thought to express approximately 2000-3000 proteins, but post translational modifications, alternatively spliced variants and a rich diversity of vertebrate domain architectures likely make this a conservative estimate. Even though rapidly advancing proteomic techniques have facilitated the identification of roughly one third of the platelet proteome, a combination of abundance-based and activity-based proteomics methodologies is needed for elucidation of platelet functional characteristics including the definition of a "core proteome" and recognition of diverse enzyme activity profiles associated with various physiological states. In this review, we describe the latest mass spectrometry based techniques capable of providing some of these physiological details required for more comprehensive evaluation of the human platelet repertoire. PMID- 22308106 TI - Adjuvant treatment of early colon cancer with micrometastases: results of a national survey. AB - BACKGROUND AND OBJECTIVES: Optimal adjuvant treatment for patients with Stage I/II colon cancer with micrometastases (MM) is unknown. Because there is no known adjuvant treatment-related benefit, we evaluated whether MM influenced treatment decisions. METHOD: Review of a national survey from members of the SSO and ASCO. RESULTS: Of 602 survey responses, 305 (51%) stated that MM had significant prognostic value, 250 (42%) were unsure, and 47 (7%) did not believe that MM held prognostic value. Three hundred seventy-four (63%) would offer adjuvant therapy in the setting of MM, while 222 (37%) would not. Only 15% routinely performed IHC on lymph nodes. Medical oncologists were more likely to recommend adjuvant therapy compared to surgical oncologists (68% vs. 51%, P = 0.001). CONCLUSIONS: MM in colon cancer apparently influenced adjuvant treatment decisions absent known prognostic benefit. Prospective trials are needed to improve the selection of patients for systemic chemotherapy in early, node-negative colon cancer. PMID- 22308105 TI - AN OVERVIEW OF ELASTOGRAPHY - AN EMERGING BRANCH OF MEDICAL IMAGING. AB - From times immemorial manual palpation served as a source of information on the state of soft tissues and allowed detection of various diseases accompanied by changes in tissue elasticity. During the last two decades, the ancient art of palpation gained new life due to numerous emerging elasticity imaging (EI) methods. Areas of applications of EI in medical diagnostics and treatment monitoring are steadily expanding. Elasticity imaging methods are emerging as commercial applications, a true testament to the progress and importance of the field.In this paper we present a brief history and theoretical basis of EI, describe various techniques of EI and, analyze their advantages and limitations, and overview main clinical applications. We present a classification of elasticity measurement and imaging techniques based on the methods used for generating a stress in the tissue (external mechanical force, internal ultrasound radiation force, or an internal endogenous force), and measurement of the tissue response. The measurement method can be performed using differing physical principles including magnetic resonance imaging (MRI), ultrasound imaging, X-ray imaging, optical and acoustic signals.Until recently, EI was largely a research method used by a few select institutions having the special equipment needed to perform the studies. Since 2005 however, increasing numbers of mainstream manufacturers have added EI to their ultrasound systems so that today the majority of manufacturers offer some sort of Elastography or tissue stiffness imaging on their clinical systems. Now it is safe to say that some sort of elasticity imaging may be performed on virtually all types of focal and diffuse disease. Most of the new applications are still in the early stages of research, but a few are becoming common applications in clinical practice. PMID- 22308108 TI - Contrast-enhanced MRI of murine myocardial infarction - part I. AB - The use of contrast agents has added considerable value to the existing cardiac MRI toolbox that can be used to study murine myocardial infarction, as it enables detailed in vivo visualization of the molecular and cellular processes that occur in the infarcted and remote tissue. A variety of non-targeted and targeted contrast agents to study myocardial infarction are available and under development. Manganese, which acts as a calcium analogue, can be used to assess cell viability. Traditionally, low-molecular-weight Gd-containing contrast agents are employed to measure infarct size in a late gadolinium enhancement experiment. Gd-based blood-pool agents are used to study the vascular status of the myocardium. The use of targeted contrast agents facilitates more detailed imaging of pathophysiological processes in the acute and chronic infarct. Cell death was visualized by contrast agents functionalized with annexin A5 that binds specifically to phosphatidylserine accessible on dying cells and with an agent that binds to the exposed DNA of dead cells. Inflammation in the myocardium was depicted by contrast agents that target cell adhesion molecules expressed on activated endothelium, by contrast agents that are phagocytosed by inflammatory cells, and by using a probe that targets enzymes excreted by inflammatory cells. Cardiac remodeling processes were visualized with a contrast agent that binds to angiogenic vasculature and with an MR probe that specifically binds to collagen in the fibrotic myocardium. These recent advances in murine contrast-enhanced cardiac MRI have made a substantial contribution to the visualization of the pathophysiology of myocardial infarction, cardiac remodeling processes and the progression to heart failure, which helps to design new treatments. This review discusses the advances and challenges in the development and application of MRI contrast agents to study murine myocardial infarction. PMID- 22308109 TI - Allenes in molecular materials. AB - This Minireview provides a critical account of the development of allene containing advanced functional materials, starting with the design and synthesis of stable and enantiopure building blocks. A variety of systems, including shape persistent macrocycles, foldamers, polymers, charge-transfer chromophores, dendrimers, liquid crystals, and redox-switchable chiral chromophores are discussed from the viewpoint of their syntheses, properties, and potential applications. The goal of this Minireview is to inspire new uses of enantiopure allenes for the rational design of advanced materials. PMID- 22308107 TI - Protein O-GlcNAcylation: A critical regulator of the cellular response to stress. AB - The post-translational modification of serine and threonine residues of nuclear and cytoplasmic proteins by the O-linked attachment of the monosaccharide beta-N acetyl-glucosamine (O-GlcNAc) is a highly dynamic and ubiquitous protein modification that plays a critical role in regulating numerous biological processes. Much of our understanding of the mechanisms underlying the role of O GlcNAc on cellular function has been in the context of chronic disease processes. However, there is increasing evidence that O-GlcNAc levels are increased in response to stress and that acute augmentation of this response is cytoprotective, at least in the short term. Conversely, a reduction in O-GlcNAc levels appears to be associated with decreased cell survival in response to an acute stress. Here we summarize our current understanding of protein O GlcNAcylation on the cellular response to stress and in mediating cellular protective mechanisms focusing primarily on the cardiovascular system as an example. We consider the potential link between O-GlcNAcylation and cardiomyocyte calcium homeostasis and explore the parallels between O-GlcNAc signaling and redox signaling. We also discuss the apparent paradox between the reported adverse effects of increased O-GlcNAcylation with its recently reported role in mediating cell survival mechanisms. PMID- 22308110 TI - Histone deacetylase inhibition in colorectal cancer cells reveals competing roles for members of the oncogenic miR-17-92 cluster. AB - Diet-derived butyrate, a histone deacetylase inhibitor (HDI), decreases proliferation and increases apoptosis in colorectal cancer (CRC) cells via epigenetic changes in gene expression. Other HDIs such as suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) have similar effects. This study examined the role of microRNAs (miRNAs) in mediating the chemo-protective effects of HDIs, and explored functions of the oncogenic miR-17-92 cluster. The dysregulated miRNA expression observed in HT29 and HCT116 CRC cells could be epigenetically altered by butyrate, SAHA and TSA. These HDIs decreased expression of miR-17-92 cluster miRNAs (P < 0.05), with a corresponding increase in miR-17 92 target genes, including PTEN, BCL2L11, and CDKN1A (P < 0.05). The decrease in miR-17-92 expression may be partly responsible for the anti-proliferative effects of HDIs, with introduction of miR-17-92 cluster miRNA mimics reversing this effect and decreasing levels of PTEN, BCL2L11, and CDKN1A (P < 0.05). The growth effects of HDIs may be mediated by changes in miRNA activity, with down regulation of the miR-17-92 cluster a plausible mechanism to explain some of the chemo-protective effects of HDIs. Of the miR-17-92 cluster miRNAs, miR-19a and miR-19b were primarily responsible for promoting proliferation, while miR-18a acted in opposition to other cluster members to decrease growth. NEDD9 and CDK19 were identified as novel miR-18a targets and were shown to be pro-proliferative genes, with RNA interference of their transcripts decreasing proliferation in CRC cells. This is the first study to identify competing roles for miR-17-92 cluster members, in the context of HDI-induced changes in CRC cells. PMID- 22308112 TI - Multiple widespread blue nodules: a clinicopathological case. AB - Glomangiomas are a variant of benign glomus tumours; glomus tumours are benign neoplastic proliferations of the glomus body, which is made up of perivascular smooth muscle cells. This forms arteriovenous anastomoses which play an important role in vascular regulation of skin temperature. The aim of this article is to describe 2 cases of hereditary glomangiomas. PMID- 22308111 TI - Immobilization on a Nanomagnetic Co/C Surface Using ROM Polymerization: Generation of a Hybrid Material as Support for a Recyclable Palladium Catalyst. AB - A novel hybrid material is reported as support for a recyclable palladium catalyst via surface immobilization of a ligand onto Co-based magnetic nanoparticles (NPs). A standard "click" reaction is utilized to covalently attach a norbornene tag (Nb-tag) to the surface of the carbon coated cobalt NPs. The hybrid magnetic nanoparticles are produced by initiating polymerization of a mixture containing both Nb-tagged ligand (Nb-tagged PPh (3)) and Nb-tagged carbon coated cobalt NPs. In turn, the norbornene units are suitably functionalized to serve as ligands for metal catalysts. A composite material is thus obtained which furnishes a loading that is one order of magnitude higher than the value obtained previously for the synthesis of functionalized Co/C-nanopowders. This allows for its application as a hybrid support with high local catalyst concentrations, as demonstrated for the immobilization of a highly active and recyclable palladium complex for Suzuki-Miyaura cross-coupling reactions. Due to the explicit magnetic moment of the cobalt- NPs, the overall magnetization of this organic/inorganic framework is significantly higher than of polymer coated iron oxide nanoparticles with comparable metal content, hence, its rapid separation from the reaction mixture and recycling via an external magnetic field is not hampered by the functionalized polymer shell. PMID- 22308113 TI - Successful Treatment of MMP-9-Expressing Angiosarcoma with Low-Dose Docetaxel and Bisphosphonate. AB - We describe a 78-year-old Japanese patient with angiosarcoma on the scalp. Interestingly, immunohistochemical staining revealed this tumor as positive for matrix metalloproteinase 9 (MMP-9). After conventional therapy for angiosarcoma with surgical treatment and radiation therapy, we intravenously administered docetaxel at 40 mg/m(2) body surface area together with oral administration of 17.5 mg sodium risedronate hydrate. One and a half years after the standard treatment, there was no evidence of local recurrence or metastasis. PMID- 22308114 TI - An ulceronecrotic foot lesion in a patient with essential thrombocythemia: successful treatment with hydroxyurea. AB - The patient was a 47-year-old woman with a painful ulcer that had appeared on the right 5th toe two weeks before she visited our hospital. Histopathological examination showed that thrombi were present in small blood vessels in the dermis and pancytosis was detected in a blood test, suggesting polycythemia-associated ulceration of the toe. Essential thrombocythemia was diagnosed based on bone marrow puncture and chromosomal test findings. Platelet count and the ulcer were improved by oral hydroxyurea. PMID- 22308115 TI - A large retinal capillary hemangioma in the anterior retina treated with photodynamic therapy. AB - PURPOSE: To report a case of a large anterior retinal capillary hemangioma (RCH) treated successfully with photodynamic therapy (PDT). METHODS: Case report. RESULTS: A 12-mm-large RCH located in the anterior retina, with vision threatening exudative complications that had not responded to cryotherapy and repeated laser photocoagulations, was treated with PDT using verteporfin. Exudation regressed and tumor growth arrested after treatment. CONCLUSION: PDT can be delivered effectively to a lesion in the anterior retina and should be included as an option for treating anteriorly located RCH when conventional cryotherapy and laser photocoagulation fail. PMID- 22308116 TI - Body image concerns and reduced breastfeeding duration in primiparous overweight and obese women. AB - OBJECTIVES: To test differences in breastfeeding duration by prepregnant maternal weight status, and determine whether body image concerns mediate any differences. METHODS: A prospective longitudinal cohort of primiparous women was followed from pregnancy to, at minimum, 6 months postpartum. Questionnaire responses on body concerns were obtained during pregnancy and at 4 months postpartum. Kaplan-Meier curves compared breastfeeding duration in overweight/obese and normal weight groups. Cox proportional hazard regression was used to determine whether body image variables mediated the relationship between maternal weight and duration. RESULTS: Although intended duration was similar between groups, overweight/obese women had a shorter median duration of any breastfeeding (38.6 weeks) compared to normal weight women (48.9 weeks) (P < 0.01) and they experienced higher risk of breastfeeding cessation over the entire first year postpartum [hazard risk (HR) = 1.43; confidence interval (CI) = 1.02-2.01; P < 0.05]. Overweight/obese women reported lack of body comfort/confidence postpartum more frequently than normal BMI women (P < 0.01). Lack of body comfort/confidence postpartum was negatively associated with duration after adjusting for maternal BMI (P = 0.01). Thus, the effect of BMI on duration was reduced by this variable (HR = 1.31; CI = 0.93, 1.86; P = 0.13), suggesting mediation. CONCLUSIONS: Women with high prepregnant BMI have reduced lactation duration that is mediated by lack of comfort/confidence with one's body. Further research into the interplay between body image, weight status, and breastfeeding outcomes may point to behavioral targets amenable to intervention and modification that may in turn improve breastfeeding outcomes for overweight/obese women and their infants. PMID- 22308117 TI - Luminescent organogold(III) complexes with long-lived triplet excited states for light-induced oxidative C-H bond functionalization and hydrogen production. AB - All that glitters is gold: highly phosphorescent gold(III) complexes with extended pi-conjugated cyclometalating ligands exhibit rich photophysical and photochemical properties. They act as efficient photocatalysts/photosensitizers for oxidative functionalizations of secondary and tertiary benzylic amines and homogeneous hydrogen production from a water/acetonitrile mixture. PMID- 22308118 TI - A Look at the Past History of Hepatitis E in Haiti: Should it be a Warning Sign during the Current Crisis? AB - Nobody can forget the devastating 7.0magnitude earthquake that struck poverty stricken Haiti, Port-au-Prince recently on 12 January 2010. At least 75,000 people were killed and hundreds of thousands became homeless; authorities are worried about sanitation and outbreaks of disease in the region. The camps are full of people and there are not even the most basic facilities for any others. Humanity obliges us to help them in any possible way. I reviewed the literature about the hepatitis E virus infection in Haiti and I would like to draw the scientists' attention to this important topic in this time of crisis. PMID- 22308119 TI - N-acetylcysteine improves liver function in patients with non-alcoholic Fatty liver disease. AB - BACKGROUND AND AIMS: Non-alcoholic fatty liver change is a common disease of the liver in which oxidative stress plays a basic role. Studies are largely focused on protecting the liver by means of anti-oxidative material. The aim of this study is to evaluate the role of N- acetylcysteine in the process of liver injury. METHODS: Thirty patients with non-alcoholic fatty liver steatosis were randomly selected to receive either N-acetylcysteine or vitamin C. Liver function tests (alanine aminotransfrase, aspartate aminotransfrase and alkaline phosphatase) were measured as well as the grade of steatosis, the pattern of its echogenicity, the span of the liver and the spleen and the portal vein diameter before the intervention. Patients were followed up using the same method of evaluation repeated in the first, second and third months. RESULTS: The mean age (SD) was 40.1(12.4) in patients receiving NAC and 46(10.4) years in patients receiving vitamin C (P = 0.137). NAC resulted in a significant decrease of serum alanine aminotransfrase after three months, compared to vitamin C. This effect was independent of the grade of steatosis in the initial diagnosis. NAC was able to significantly decrease the span of the spleen. CONCLUSIONS: N-acetylcysteine can improve liver function in patients with non-alcoholic fatty liver disease. Better results may be achievable in a longer follow up. PMID- 22308120 TI - Persistence of HBV Vaccine's Protection and Response to Hepatitis B Booster Immunization in 5- to 7-Year-Old Children in the Kohgiloyeh and Boyerahmad Province, Iran. AB - BACKGROUND AND AIMS: The duration of the protection of hepatitis B vaccination for infants and the necessity of a booster dose administration is unknown. The aim of the present study was to evaluate the persistence of seroprotection after hepatitis B virus (HBV) vaccination in order to determine the necessity of a single booster dose in 5- to 7-year-old children. METHODS: This clinical trial study was conducted from 2004 to 2005.The study population included all children aged 5 to 7 years old in the Kohgiloyeh and Boyerahmad province who had been vaccinated starting at birth with hepatitis B vaccine. Among these children, 729 were selected via a multiple-stage sampling method. Parents gave their informed consent, and blood specimens (3 ml) were obtained from children. Hepatitis B surface antibody (HBsAb) and hepatitis B surface antigen (HBsAg) were determined by enzyme-linked immunosorbent assay (ELISA). Subjects with nonprotective titer levels (< 10 mIU/ml) received a booster does of the DNA recombinant vaccine. Four weeks after the administration of a booster dose, the antibody to HBsAg (anti HBs) titer was measured. Data were analyzed using SPSS software, and analyses included chi-square, ANOVA, and independent-samples and paired-samples t-tests. RESULTS: 615 children (84.4%) had a protective antibody titer. The mean antibody titer was 230.5 +/- 308.9 IU/ml, with a range of 10.6 to 1175 IU/ml. 15.6% of subjects had a nonprotective antibody titer, and the mean antibody titer was 4.97 +/- 3.5 IU/ml. All subjects were HBsAg negative. No statistically significant differences were found by sex or by urban versus rural area of residence. The seroprotection rates significantly decreased by as the age of the children increased.Following the booster dose, 78.1 % of the children had a protective titer, and the mean titer significantly increased from 4.97 +/- 3.5 at birth to 332.1 +/- 402 IU/ml after the booster (P < 0.001). CONCLUSIONS: According to our results, the proper response of the immune system to a booster dose of HBV at 5 to 7 years of age reveals that immunologic memory is good after primary vaccination. Administration of booster dose does not appear to be necessary at these ages even though these children have a greater possibility of exposure to HBV in school age. PMID- 22308121 TI - Detection of hepatitis B virus in used razor blades by PCR. AB - BACKGROUND AND AIMS: Hepatitis B virus (HBV) infection ranks among the most devastating health problems in the world.The most probable transmission routes of HBV are blood contact, sexual, and horizontal transfer. Other sources of HBV transmission are razor sharing, beauty treatments, tattooing, piercing, and manicures and other chiropody treatments.Many infections have been reported in South-East Asia, where barbers commonly share and reuse razors. Detection of HBV DNA in contaminated devices such as razor blades is important in the demonstration of transmission routes and indirect estimation of HBV prevalence in specific subpopulations such as barbershop clientele. Therefore, we aimed to detect the presence of HBV contamination on razor blades by nucleic acid testing. METHODS: Used razor blades (n = 151) were purchased from different barber's shops. Used razor blades purchased from chronic HBV patients (n = 8) were included as a positive control. The amplification and detection of HBV DNA was carried out by a semi-nested PCR method in a thermal cycler. RESULTS: The presence of HBV DNA was found in 10 (6.6%) used razor-blade samples by the detection of a specific positive band with agarose gel electrophoresis. CONCLUSIONS: In conclusion, used razor blades may be contaminated with HBV, and the practice of sharing used razor blades may pose a risk of transmission. Nucleic acid detection methods involving PCR can be used to detect HBV contamination of razor blades. HBV control and prevention programs should educate barbers about the importance of contagious diseases, proper sterilization techniques, and avoiding reuse and sharing of contaminated equipment and supplies such as razor blades. As an infection control measure, prohibition of razor reuse can reduce the spread of HBV infection in rural areas, where the practice is often common at barbershops. PMID- 22308122 TI - Evaluation of the Prevalence of Hepatitis B, Hepatitis C, and HIV in Inmates with Drug-Related Convictions in Birjand, Iran in 2008. AB - BACKGROUND AND AIMS: Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) are common infections among prisoners. Addicted prisoners are at a higher risk than the normal population for contracting these diseases. Many studies have reported higher prevalence rates of HBV, HCV, and HIV in prisoners. Because of this problem, this study was conducted to evaluate the serologic prevalence of these three diseases in prisoners convicted of drug related crimes. METHODS: A descriptive cross-sectional study was conducted on a random sample of prisoners with drug charges who were inmates in a prison in Birjand, Iran. Information was collected via questionnaire after obtaining prisoners' informed consent and blood samples were tested for hepatitis B surface antigen (HBsAg), antibodies to HCV (anti-HCV), and antibodies to HIV (anti-HIV). The results were analyzed by chi-square tests. RESULTS: In this study, 358 prisoners were selected. 80.2% of prisoners were male, and 19.8% were female. The average age was 34.7+/-12 years. 39.1% were addicted to drugs, 54.2% were smokers, and 19.3% had tattoos. 8.4% had had extramarital intercourse, and 16.8% had had a sexually transmitted disease (STD) in past. HBsAg, anti-HCV, and anti- HIV prevalence in these samples were 6.1%, 8.1%, and 0%, respectively.The prevalence rate of HBV in the addicted prisoners was 4.3%, and the rate in non addicted prisoners was 7.3% (P = 0.24).The prevalence of HCV in addicted prisoners was 15.7%, and the prevalence in non-addicted prisoners was 3.2%; this difference was significant (P < 0.001).Furthermore, a significant difference between the prevalence of HBV and extramarital intercourse was noted (P < 0.005).A significant difference between HCV and transfusion, history of STDs, addiction, and tattooing was noted. CONCLUSIONS: The survey showed that HCV, HBV, and HIV prevalence rates in prisoners were 8.1%, 6.1%, 0%, respectively. The prevalence rates of HCV and HBV in addicted prisoners were 15.7% and 4.3 %, respectively. Studies performed in Iran and other countries have shown that the prevalence rates of HBV, HCV, and HIV in addicted prisoners were higher than the rates in non-addicted prisoners. These results indicate that HBV, HCV, and HIV are significant problems in prisons, and efforts to reduce the risk of these infections, such as education and vaccination, should be considered. PMID- 22308123 TI - Serum Levels of IL-10 and IL-17A in Occult HBV-Infected South-East Iranian Patients. AB - BACKGROUND AND AIMS: Occult hepatitis B infected (OBI) patients can not completely eradicate hepatitis B virus-DNA (HBV-DNA) from their liver and peripheral blood. The main aim of this study was to investigate the Interleukin (IL)-10and IL-17A serum levels in patients suffering from OBI. MATERIAL AND METHODS: In this observational study, plasma samples of 3700 blood donors were tested for hepatitis Bsurface antigen (HBsAg) and antibodies to the hepatitis B core antigen (anti-HBc), using enzyme-linked immunosorbent assay (ELISA). The HBsAg-/anti-HBc+ samples were selected and screened for HBV-DNA, using the polymerase chain reaction (PCR). HBV-DNA positive samples were assigned as OBI cases and IL-10 and IL-17 serum levels were detected using ELISA. RESULTS: The results demonstrated that, 352 (9.5%) out of 3700 blood samples were HBsAg-/anti HBc+ and HBV-DNA was detected in 57/352 (16.1%) of the HBsAg-/anti-HBc+ samples. Our results showed that the IL-10 and IL-17A serum levels increased significantly in the OBI cases in comparison to the controls (P < 0.001). CONCLUSIONS: According to the results of this study the higher level of IL-10 production may suppress the functioning of the immune system against HBV in OBI patients. The elevated IL-17A serum level also indicates a long period of infection in the patients observed. PMID- 22308124 TI - Seroprevalence of Hepatitis B and C among Children in Endemic Areas of Turkey. AB - BACKGROUND AND AIMS: Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infections are major worldwide public health problems. The objectives of this study were to evaluate the seroprevalence and epidemiological profile of hepatitis B and hepatitis C, to determine the impact of the national vaccination programme against hepatitis B on the prevalence of the hepatitis B surface antigen (HBsAg) carrier and the antibody to hepatitis B surface antigen (anti HBs) occurrence rate among 0-14 year-old children in southeast Turkey. METHODS: The seroprevalence of hepatitis B and hepatitis C markers was evaluated retrospectively in a group of 10,391 children who were admitted to a tertiary hospital, the Diyarbakir Education and Research Hospital, from January 2005 to December 2008, in order to obtain a better understanding of the regional hepatitis seroprevalence. Children were divided into three different age groups: pre-education period (0-6 years), primary school period (7-12 years) and secondary school period (13-14 years). Samples were analyzed for HBsAg, hepatitis B e antigen (HBeAg), antibody to HBeAg (anti-HBe), anti-HBs positive/antibodies to hepatitis B core antigen (anti-HBc) positive, isolated anti-HBs and antibodies to Hepatitis C virus (anti-HCV) using a commercially available enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean age of all participants was 8.5+/- 2 years (range, 0-14). The overall percentages for the prevalence of HBsAg, HBeAg, anti-HBe and anti-HCV were 8.1%, 2.1%, 5.9% and 0.5%, respectively. HBsAg seroprevalence differed significantly by age and gender (P < 0.001). HBeAg seroprevalence was high in the earliest years (P < 0.01). The overall prevalence of anti-HCV did not differ significantly by age (P > 0.5) but differed by gender (P < 0.001). The overall percentages for the prevalence of isolated anti-HBs and anti-HBs positive/anti-HBc positive were 34.2% and 56.9%,respectively. CONCLUSIONS: Our study sheds new light on hepatitis seroprevalence in southeastern Turkey. For example, 1) The seroprevalence of hepatitis B in southeast Turkey is still at its highest rate, according to the averages reported in other studies conducted in the same and different regions of Turkey; and it has not decreased, as reported previously. 2) HBeAg seroprevalence in the earliest years of childhood is high in our study; this is evidence for early acquisition of the infection.3) Isolated anti-HBs positive and anti-HBs positive/anti-HBc positive prevalence is high; given these features, it is obvious that despite the high incidence of vaccinated children, the prevalence of hepatitis B is increasing; and children acquire these viruses in their earliest years. 4) We found the overall prevalence of HCV infection unchanged. Our region has a low endemicity for HCV. PMID- 22308125 TI - Molecular diagnosis of entecavir resistance. AB - Entecavir (ETV) is a potent nucleoside analogue against hepatitis B virus (HBV). Because of development of ETV resistance requires at least three amino acid substitutions in HBV polymerase (pol) gene, emergence of ETV resistance is rare (~1%) in nucleoside-naive patients after up to 5 years of treatment. However, it has been suggested that lamivudine (LAM) therapy can preselect for HBV variants associated with resistance to ETV treatment. ETV resistance increased to 51% of patients after 5 years of ETV treatment in LAM refractory patients. The diagnosis of ETV resistance in chronic hepatitis B patients, mainly based on four types of molecular assays: direct sequencing, line probe assay, clonal analysis,and restriction fragment length polymorphism (RFLP) analysis. The applications of other assays are currently more specialized,and their use is more limited. The utility of these assays and their performance characteristics are reviewed below.Briefly, the monitoring of drug-resistant variants is important in the elucidation of the prevalence and mechanisms of resistance development and for the more effective management of treatment options. PMID- 22308126 TI - A woman with recent jaundice and pruritus. AB - A middle-aged woman suffering from jaundice and pruritus that had begun a month previously was presented to a physician.At the first assessment, laboratory findings had revealed a cholestatic pattern and serologic tests for hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis A virus (HAV) were negative. Normal findings of abdominal computed tomography (CT) scan and endoscopic retrograde cholangiopancreatography (ERCP) ruled out extrahepatic causes of cholestasis. A liver biopsy was done and showed intrahepatic cholestasis without destruction of the bile ducts or granuloma.We assessed the intrahepatic causes of cholestasis. Finally the diagnosis was confirmed by means of a simple test. PMID- 22308127 TI - A used ball of cotton wool as a source of nosocomially-acquired hepatitis C infection. AB - BACKGROUND AND AIMS: An error involving the reuse of the same ball of cotton wool in stopping blood flow after venous blood collection from five antenatal women prompted further investigation and follow-up studies to rule out nosocomially acquired blood borne viruses. METHODS: The five women were screened for antibodies to the human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B surface antigen (HBsAg), using enzyme-linked immunosorbent assay (ELISA) /kits Murex HIV-1- ,2,0 (Murex Biotech, UK); ORTHO HCV 3.0 ELISA Test kit (Ortho Clinical Diagnostics, USA); and QUADRATECH CHECK 4-HBs one-step generation test kit (VEDALAB, France) respectively. The tests were repeated in 2005 on the five women, their husbands and twenty children, aged nine months to seven years borne by all the women within the period. Anti-HCV was detected in one out of the five women at the initial stage of the error (1997). No anti-HIV or HBsAg was found in any of the women. A repeat screening for anti-HIV, anti-HCV and HBsAg carried out seven years later (2005) on the five women, their husbands and twenty children aged nine months to seven years borne by all the women within the seven years revealed an HCV sero-conversion in two additional women. No anti-HCV or anti-HIV nor HBsAg was detected in any of the women, their spouses or their 20 offspring. RESULTS: Anti-HCV was detected in one out of the five women at the initial stage of the error (1997). No anti-HIV or HBsAg was detected in any of the women. A repeat re-evaluation revealed an HCV sero-conversion in two additional women. No anti-HCV or anti-HIV nor HBsAg was detected in any of the women, their spouses or any of their 20 screened offspring. CONCLUSIONS: This study provides evidence for the nosocomial transmission of HCV through the use of a contaminated ball of cotton wool. It also confirms the poor efficiency of sexual and vertical transmission of HCV and calls for improved hospital facilities and the use of skilled staff to perform essential duties. PMID- 22308128 TI - Nintinol self-expandable metallic stenting in management of malignant obstructive jaundice: a case series. AB - BACKGROUND AND AIMS: Palliation therapy is the only available therapeutic method for most patients with tumor-induced obstructive jaundice. Metallic stents are now performed percutaneously as an alternative route to the endoscopic approach. It is widely accepted because of its safety, good patency rate, and minimal invasiveness. This study was designed to evaluate the long-term results of metallic self-expandable stent insertion in patients with malignant stenosis of the biliary tree. METHODS: It is a longitudinal study of patients with percutaneously biliary stenting from September 2005 to March 2009. The patients had unresectable malignant biliary obstruction with unsuccessful endoscopic stenting and access. Percutaneous transhepatic cholangiogram performed after adequate local anesthesia, under sonographic or fluoroscopic guidance. Stenting or balloon dilation was performed through the hydrophilic guide wire. Among 50 patients, 45 stents were placed in biliary tree stenosis sites. Patients' follow up was during the first, second, third, and then the sixth month after insertion of biliary stents. Stent patency was considered successful in our patients, when there were no lab results or sonographic appearance of biliary tree obstruction. RESULTS: 10(20%) patients' stent placement treatment failed because of unsuccessful technical procedure. The stenosis of biliary tract was complete and passage of guide wire was not possible through the tumor growth. 6 (15 %) patients with successful stent placements died within one month (mean, 22 days). Total serum bilirubin resolved to below 1.5 mg/dl within 30 days for 36 (90%) patients with successful stent placements. Early complications not leading to death occurred in 28% of cases. The mean survival time for all patients who underwent stent placement was 140 days (16-420days). The mean patency rate for all stents was 147 days. CONCLUSIONS: Percutaneous biliary stenting is a safe procedure with few technical complications and a high success rate of palliation for patients with malignant biliary jaundice. Early complications are mostly managed conservatively and death is mainly due to systemic effects of the malignant disease. PMID- 22308129 TI - Evaluation of Zinc Plasma Level in Iranian Cirrhotic Patients due to Hepatitis B and Hepatitis C. AB - BACKGROUND AND AIMS: Zinc (Zn) has various significant roles in physiological functions of the liver. Furthermore, it has been reported that the administration of zinc has an important role in pharmacotherapy of viral hepatitis. Cirrhotic patients with decrease in plasma zinc level have been covered in previous studies. It is seemingly necessary to assess the zinc level, in Iranian cirrhotic patients, as a distinct population, Because of the large phytate amounts in Iranians diet. Regarding to etiology, disease progress, and treatment, there are some differences in the 2 most common causes of cirrhosis in the Iranian population (hepatitis B and hepatitis C) and it is possible that the zinc level may be different between the two. This study was done to shadow some lights on the subject. METHODS: Between April 2008 and November 2008, plasma zinc level was determined, by atomic absorption method, in 60 cirrhotic inpatients treated due to hepatitis B or hepatitis C in Talighani hospital (a referral center for gastrontestinal and liver diseases in Tehran, Iran). RESULTS: Mean +/- standard deviation (SD) plasma zinc levels determined 0.34+/-0.22 mg/L and 0.37+/-0.22 mg/L in hepatitis B and hepatitis C patients respectively. Analysis of t-test showed there is no significant difference between 2 groups regarding to plasma zinc level (P = 0.745). CONCLUSIONS: It is concluded that zinc level of studied cirrhotic patients is less than half of the normal range. Moreover, there is no difference in plasma zinc level between cirrhotic patients due to hepatitis B or hepatitis C. Regarding to this result, supplementation with complementary zinc, may be recommended in both groups in order to optimize the nutritional support and probably better the treatment response. PMID- 22308130 TI - Isolation of hepatitis C virus in norjizac vials. PMID- 22308131 TI - Thermodynamic imbalance, surface energy, and segregation reveal the true origin of nanotube synthesis. AB - Extensive analyses of thermodynamic imbalance, surface energy, and segregation of nanotubes on nanoparticle surfaces are performed. A model for surface energy i developed. In addition, nanotube growth both by vapor-phase and solid-phase mechanisms is described. Segregation of the nanotube species to the periphery of the nanoparticle, the creation of an amorphous shell at this periphery, a droplet created in this shell, and the mediation of this droplet for supersaturation and nucleation of the nanotube species may be the true causes of nanotube growth. PMID- 22308132 TI - Hepatitis C virus and lichen planus: the real association. PMID- 22308133 TI - Type of pegylated interferon matters: another milestone in the treatment of hepatitis C virus infection. PMID- 22308134 TI - Determination of the relationship of serum hyaluronic Acid levels to the degree of liver fibrosis in biopsies of patients with chronic viral hepatitis B and C. AB - BACKGROUND AND AIMS: Determining the stage of liver fibrosis and the grade of necroinflammation is important in predicting the prognosis and treatment response of patients with chronic viral hepatitis. Liver biopsy is associated with several technical problems and complications; therefore, its repetitive performance as a procedure in evaluating treatment response and in following up patients is not recommended. This study was performed to determine the correlation of serum hyaluronic acid (HA) levels with the stage and grade of histopathologic liver changes in patients with chronic hepatitis B and C. METHODS: This analytical cross-sectional study was performed on 69 patients with chronic hepatitis B or C in Mashhad, Iran, who were referred to our clinic and underwent liver biopsy and blood sampling simultaneously in 2006-2007. None of the patients were on medication that would affect the serum levels of (HA) and patients with signs of arthropathy were excluded from the study. RESULTS: Out of the 69 patients i this study, 48 (69.6%) were male and 21 (30.4%) were female. The causative virus in 29 patients (42%) was hepatitis C and in the rest (n = 40, 58%) hepatitis B. The severity of liver fibrosis (stage) had a direct correlation (r = 0.25, P = 0.042) with the levels of (HA) and an inverse correlation with the platelet level (r = 0.37, P = 0.002). The degree of liver necroinflammation (grade) did not have a significant correlation with the levels of (HA) and alanine transaminase (r = 0.01, P = 0.9; r = 0.21, P = 0.09 respectively); instead, there was an inverse correlation with platelet levels (r = 0.36, P = 0.003). CONCLUSIONS: Our study results correspond with those of other international studies; thus suggesting that the (HA) serum level is a useful marker in determining the severity of fibrosis in patients with chronic viral hepatitis. To form a definite conclusion, further studies on large groups should be performed. PMID- 22308135 TI - Are hepatitis B virus and celiac disease linked? AB - BACKGROUND AND AIMS: It has been hypothesized that nonintestinal inflammatory diseases such as hepatitis B virus (HBV) and hepatitis C virus (HCV) may trigger immunologic gluten intolerance in susceptible people. This hypothesis suggests a possible epidemiological link between these two diseases, although this assumption is still a matter of debate. METHODS: We conducted a retrospective study to assess the prevalence of celiac disease in HBV carrier patients who had been infected in childhood. RESULTS: None of the HBV carrier patients had immunoglobulin A antiendomysium and immunoglobulin A anti-tissue transglutaminase, but 6 patients and 1 recovered subject had immunoglobulin A antigliadin and/or immunoglobulin G antigliadin. Moreover, no patient treated with interferon therapy showed any serological marker of celiac disease. CONCLUSIONS: Due to the small sample size, we cannot claim that there is no association between celiac disease (CD) and HBV, although in our study we did not find any CD patients. A sample size that is more representative of the prevalence of CD in Italy would better support the establishment of any possible connection between CD and HBV. PMID- 22308136 TI - Knowledge, attitudes and practice of Iranian medical specialists regarding hepatitis B and C. AB - BACKGROUND AND AIMS: Health care workers (HCWs) are at risk of contracting and spreading hepatitis B virus (HBV) and hepatitis C virus (HCV) to others. The aim of this study was to evaluate knowledge, attitudes and behavior of physicians concerning HBV and HCV. METHODS: A 29-item questionnaire (reliability coefficient = 0.7) was distributed at two national/regional congresses and two university hospitals in Iran. Five medical groups (dentists, general practitioners, paraclinicians, surgeons and internists) received 450 questionnaires in 2009, of which 369 questionnaires (82%) were filled out. RESULTS: Knowledge about routes of transmission of HBV and HCV, prevalence rate and seroconversion rates secondary to a needlestick injury was moderate to low. Concern about being infected with HBV and HCV was 69.4+/-2.1 and 76.3+/-2 (out of 100), respectively. Complete HBV vaccination was done on 88.1% of the participants. Sixty percent had checked their hepatitis B surface antibody (anti-HBs), and 83.8% were positive. Only 24% of the surgeons often used double gloves and 28% had reported a needlestick. There was no significant correlation between the different specialties and: concern about HBV and HCV; the underreporting of needlestick injuries; and correct knowledge of post-needlestick HBV infection. CONCLUSIONS: Although our participants were afraid of acquiring HBV and HCV, knowledge about routes of transmission, prevalence, protection and post-exposure seroconversion rates was unsatisfactory. By making physicians aware of possible post-exposure prophylaxis, the underreporting of needlestick injuries could be eliminated. Continuous training about HBV and HCV transmission routes, seroconversion rates, protection, as well as hepatitis B vaccination and checking the anti-HBs level, is a matter of necessity. PMID- 22308137 TI - Entecavir therapy in Turkish adult patients with chronic hepatitis B: one-year results from Izmir province, Turkey. AB - BACKGROUND: In the present study, we aimed to present the initial results of chronic hepatitis B patients who received entecavir (ETV) therapy in our hospital in Izmir, Turkey. METHODS: A total of 52 patients were enrolled in the study. ETV was given in a dosage of 0.5 mg/day and 1 mg/day to 50 patients without Lamivudine/Adefovir (LAM/ADV) resistance and to 2 patients with LAM resistance, respectively. ETV was given in a dose of 0.5mg/day every three days to one patient with a renal transplant. The treatment duration was 48 weeks. RESULTS: Out of a total of 52 patients, 23 (44.23%) were hepatitis B e antigen (HBeAg) positive, and 29 (55.77%) of them were HBeAg-negative. In 29 HBeAg-negative patients, early biochemical and virological responses were 82.6% and 100%, respectively. These responses were 97% and 79.3% in the 12th month. In HBeAg positive patients, early biochemical and virological responses were found to be 78.3% and 82.6%, respectively. They were 100% and 52.2% in the 12th month. HBeAg s oconversion developed in 4.5% of HBeAg-positive patients. CONCLUSIONS: According to our one-year ETV treatment results, both HBeAg-negative and positive patients had high biochemical and virological response rates. Their HBeAg seroconversion rate was 4.5%. In conclusion, more studies of longer duration are needed to understand the required duration of treatment, to assess its long-term effectiveness, and to check the resistance and side effects of ETV. There is also a need to have late-phase results after treatment. PMID- 22308138 TI - Hepatitis B and C among patients infected with human immunodeficiency virus in Isfahan, Iran: seroprevalence and associated factors. AB - BACKGROUND AND AIMS: Patients with human immunodeficiency virus (HIV) are also likely to be at risk for other infectious pathogens including hepatitis B(HBV) and C(HCV) viruses, which complicate the clinical course, management, and therapy. The literature on the prevalence of HBV/HCV coinfection with HIV in Iran is sparse. Hence this study was conducted to investigate this coinfection pattern and its risk factors in Isfahan, Iran. METHODS: All of the HIV-infected patients attending clinics for acquired immune deficiency syndrome (AIDS) research and education in Isfahan province during the period of May 1998 through April 2007 were included in this cross-sectional study. After giving their informed consent, the patients were screened for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV), and anti-HCV-positive cases were confirmed with the RIBA test. The demographic data and information about risk behaviors were collected as well. Multivariate logistic regression was used to identify independent risk factors for HBV and HCV. RESULTS: The subjects included 130 patients (128 males and 2 females) with a mean age of 50.23 +/- 8.81 years. Most of the subjects were unemployed (61.5%) and single (56.2%). A history of imprisonment, ,intravenous drug abuse, and high-risk sexual activity were reported by 83.7%, 83.5%, and 48% of the subjects, respectively. Coinfection with hepatitis viruses was observed in 78.5% of the subjects. Low levels of education, a history of imprisonment, and youth were the main risk factors for HCV/HIV coinfection (OR = 196, 114, and 0.9 respectively). CONCLUSIONS: Our study showed that there is a high prevalence rate of HCV/HIV coinfection in Isfahan, Iran, with the major risk factor being a history of imprisonment. PMID- 22308139 TI - European vs. Egyptian HCV-4 patients with elevated baseline HCV RNA, treated with PEG-IFN-alpha2a and ribavirin: the role of rapid and early virologic response. AB - BACKGROUND AND AIMS: Despite the recent spread of hepatitis C virus genotype 4 (HCV-4) into European countries, very little is known about the influence of ethnicity on treatment outcomes in patients with HCV-4. The aim of this study was to compare the virologic response (VR) rates of: rapid virologic response (RVR), early virologic response (EVR), VR at 24 weeks of treatment, at end of treatment (EoT), and sustained virologic response (SVR) of European and Egyptian HCV-4 patients. METHODS: Sixty (30 Europeans - Group A; and 30 Egyptians - Group B) chronic HCV-4 subtype A adult patients with elevated baseline viral load (>800 000 IU/m L) were treated for a fixed period of 48 weeks with pegylated interferon alpha2a (PEG-IFN- alpha2a) and ribavirin. During the study, HCV-RNA levels were measured at weeks 4,12,24,48 and 72. RESULTS: Baseline characteristics, including liver histology, were similar in the two groups. RVR, EVR and HCV-RNA at week 24 in Groups A and B were (RVR 26.7% vs. 30.0%) (EVR 23.3% vs. 16.7%) (in week 24 13.3% vs. 16.7%). Overall SVR rates were 36.7% (11/30) for Group A and 26.7% (8/30) for Group B (P = 0.59). For group B, RVR was the weakest indicator for SVR as compared with RVR of group A, where RVR was the best SVR indicator CONCLUSIONS: The overall response to treatment was similar, but ethnic origin or previous history and treatment of schistosomiasis may influence intermediate response rates of chronic HCV-4a infected patients with elevated baseline HCV RNA. PMID- 22308140 TI - Hepatitis C in Pakistan: a review of available data. AB - Hepatitis C virus (HCV) infection is increasingly recognized as a major health care problem, and is found frequently in Pakistani settings. In this article we reviewed published and unpublished data related to the seroepidemiology of HCV infection in Pakistan. For this article, data from 132 published studies and three unpublished data sets published/ presented between the period 1992-2008 were utilized. Data of 1,183,329 individuals were gathered. Blood donors (982,481) and the general population (178,322) constituted the majority of these subjects. The frequency of HCV infection in blood donors and in the general population was 3.0 % (95% CI: 3.0- 3.1) and 4.7 (95% CI: 4.6 -4.8), respectively. The frequency among 6,148 pregnant females was 7.3% (95% CI = 6.7 - 8.0). The frequency in healthy children ranged from 0.4 to 4.1% (95% CI = 1.4 - 2.3). Pakistani HCV serofrequency figures are significantly higher (P < 0.0001) compared to those of the corresponding populations in surrounding countries like India, Nepal, Myanmar, Iran and Afghanistan. PMID- 22308141 TI - Amazing results with hydroxyurea therapy in chronic hepatitis B: a preliminary report. AB - BACKGROUND AND AIMS: To introduce the possible role of hydroxyurea (HU), a well characterized antineoplastic drug with established antiviral effects, in the treatment of chronic hepatitis B. METHODS: Four antiretroviral-naive patients with chronic hepatitis B were enrolled in this limited pilot trial, and given 1000 mg/day of hydroxyurea for 4 weeks; then, the administration of the drug was suspended for 4 weeks. A clinical study and laboratory safety assessments and measurements of viral load were made at baseline, after drug therapy, and after one month suspension of the treatment RESULTS: All 4 patients showed a significant decrease in viral load after 4 weeks of hydroxyurea therapy and the viral load of 2 patients increased again after a 4-week suspension of hydroxyurea CONCLUSIONS: Our data demonstrate that the old low-cost antineoplastic drug, hydroxyurea, efficiently blocks hepatitis B virus (HBV) replication. We suggest that HU will play an important role in the treatment of chronic hepatitis in the foreseeable future. Further studies including those that evaluate optimal dosing in long-term use will continue to define the role of HU in the treatment of HBV infection alone or in combination with other antiviral drugs. PMID- 22308142 TI - The effect of education on quality of life in patients under interferon therapy. AB - BACKGROUND AND AIMS: The main purpose of treating and caring for patients with chronic viral hepatitis is to promote life satisfaction and a feeling of well being in patients suffering from this disease. The aim of this study was to evaluate the effect of education on quality of life in patients with chronic hepatitis who were treated with Interferon alpha. METHODS: This quasi experimental study was conducted on 60 patients with viral hepatitis. The intervention included teaching them the method of self injection of Interferon alpha 2 b, giving them educational pamphlets and then following their continuing treatment with interferon. Patients were randomly assigned to two 30-patient groups. The data- gathering tool was a demographic characteristics questionnaire and the Quality of Life Questionnaire for Patients with Chronic Liver Disease (CLDQ). The educational program was done in four 45- minute sessions for the case group and their relatives. The follow-up period was 12 weeks. Quality of life in patients with chronic hepatitis was measured before initiating interferon therapy, and after the educational period. Quality of life in the two groups was compared. RESULTS: The total quality of life score in the two groups before therapy did not show any significant difference (P = 0.351); while 12 weeks after education there was a significant difference between the two groups (P < 0.001) in three items including abdominal symptoms (P = 0.01), worry (P < 0.001) and emotional factors (P < 0.001). The other three items did not show a significant difference between the two groups. The total quality of life score in the case group was significantly different before and after education (P < 0.001), and improved after education. The total quality of life score in the control group did not differ significantly after 12 weeks (P = 0.143). CONCLUSIONS: Planning short and simple educational programs has a significant effect on the patient's control of his/her disease and its side effects; and can improve quality of life, life satisfaction, and mechanisms of coping with treatment in patients with viral hepatitis. PMID- 22308143 TI - Which is the IDEAL peginterferon for Hepatitis C: a meta-analysis of both pegylated interferons in the treatment of HCV-infected patients. PMID- 22308144 TI - Interferon-based therapy for chronic hepatitis C: current and future perspectives. PMID- 22308145 TI - Efficacy of peginterferon alpha-2a vs. 2b for the treatment of chronic HCV: interpretation of results and future prospects. PMID- 22308146 TI - Interferon: a sharp sword to overcome HCV or HBV-related liver diseases? PMID- 22308147 TI - IDEOM: an Excel interface for analysis of LC-MS-based metabolomics data. AB - SUMMARY: The application of emerging metabolomics technologies to the comprehensive investigation of cellular biochemistry has been limited by bottlenecks in data processing, particularly noise filtering and metabolite identification. IDEOM provides a user-friendly data processing application that automates filtering and identification of metabolite peaks, paying particular attention to common sources of noise and false identifications generated by liquid chromatography-mass spectrometry (LC-MS) platforms. Building on advanced processing tools such as mzMatch and XCMS, it allows users to run a comprehensive pipeline for data analysis and visualization from a graphical user interface within Microsoft Excel, a familiar program for most biological scientists. AVAILABILITY AND IMPLEMENTATION: IDEOM is provided free of charge at http://mzmatch.sourceforge.net/ideom.html, as a macro-enabled spreadsheet (.xlsb). Implementation requires Microsoft Excel (2007 or later). R is also required for full functionality. CONTACT: michael.barrett@glasgow.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22308148 TI - Improving your target-template alignment with MODalign. AB - SUMMARY: MODalign is an interactive web-based tool aimed at helping protein structure modelers to inspect and manually modify the alignment between the sequences of a target protein and of its template(s). It interactively computes, displays and, upon modification of the target-template alignment, updates the multiple sequence alignments of the two protein families, their conservation score, secondary structure and solvent accessibility values, and local quality scores of the implied three-dimensional model(s). Although it has been designed to simplify the target-template alignment step in modeling, it is suitable for all cases where a sequence alignment needs to be inspected in the context of other biological information. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at http://modorama.biocomputing.it/modalign. Website implemented in HTML and JavaScript with all major browsers supported. CONTACT: jan.kosinski@uniroma1.it. PMID- 22308149 TI - Discriminating response groups in metabolic and regulatory pathway networks. AB - MOTIVATION: Analysis of omics experiments generates lists of entities (genes, metabolites, etc.) selected based on specific behavior, such as changes in response to stress or other signals. Functional interpretation of these lists often uses category enrichment tests using functional annotations like Gene Ontology terms and pathway membership. This approach does not consider the connected structure of biochemical pathways or the causal directionality of events. RESULTS: The Omics Response Group (ORG) method, described in this work, interprets omics lists in the context of metabolic pathway and regulatory networks using a statistical model for flow within the networks. Statistical results for all response groups are visualized in a novel Pathway Flow plot. The statistical tests are based on the Erlang distribution model under the assumption of independent and identically Exponential-distributed random walk flows through pathways. As a proof of concept, we applied our method to an Escherichia coli transcriptomics dataset where we confirmed common knowledge of the E.coli transcriptional response to Lipid A deprivation. The main response is related to osmotic stress, and we were also able to detect novel responses that are supported by the literature. We also applied our method to an Arabidopsis thaliana expression dataset from an abscisic acid study. In both cases, conventional pathway enrichment tests detected nothing, while our approach discovered biological processes beyond the original studies. AVAILABILITY: We created a prototype for an interactive ORG web tool at http://ecoserver.vrac.iastate.edu/pathwayflow (source code is available from https://subversion.vrac.iastate.edu/Subversion/jlv/public/jlv/pathwayflow). The prototype is described along with additional figures and tables in Supplementary Material. CONTACT: julied@iastate.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22308150 TI - Implications of confidential unit exclusion in providing sufficient safe blood for the national health system. PMID- 22308151 TI - Treatment of HCV patients before and after renal transplantation. AB - CONTEXT: Patients with end-stage renal disease can easily acquire a hepatitis C virus (HCV) infection via several ways. An HCV infection is difficult to treat after renal transplantation due to the conflicting actions of immunosuppressant therapy to maintain the function of the transplanted kidney and viricidal interferon (IFN) or ribavirin (RBV) treatment. Antiviral therapy requires great caution to avoid the complex and potentially fatal pharmacological effects. In this review, we examined clinical challenges and potential solutions for this specific scenario. EVIDENCE ACQUISITIONS: We searched Pubmed (NLM), LISTA (EBSCO), Web of Science (TS). The management of patients on waiting list, the indications and regimens about treatment were studied. RESULTS: More than forty papers about this topic were found, including seven small clinical trials. International consensus has been reached to test patients awaiting renal transplantation. HCV detection after renal transplantation warrants careful consideration of when to initiate antiviral therapy. Treatment will begin immediately if deteriorating liver function increases the risk for loss of renal function. The choice of regimen depends on the patient's renal function and is individualized under close observation. The immunosuppressive regimen will be adjusted accordingly before antiviral therapy is initiated. CONCLUSIONS: The effects of modified antiviral therapy on these patients varies because of individual characteristics and disease state, and also because of the difficulty associated with conducting a large clinical trial to obtain statistically sound conclusions. The management before transplantation is important and when antiviral therapy needs to start, careful consideration of risks and benefits is needed before initiating this type of treatment. PMID- 22308152 TI - Frequency of Two Common HFE Gene Mutations (C282Y and H63D) in a Group of Iranian Patients With Cryptogenic Cirrhosis. AB - BACKGROUND: The human HFE gene (a key component of iron homeostasis in humans) is involved in hereditary hemochromatosis, a common autosomal recessive genetic disorder that is characterized by excessive intestinal iron absorption and progressive iron overload. OBJECTIVES: In this study, we assessed the frequency of two common forms of hemochromatosis HFE gene mutation (C282Y and H63D) in patients suffering from cryptogenic cirrhosis. PATIENTS AND METHODS: One hundred and fifty individuals were included in this study, in which 100 were patients with cryptogenic cirrhosis and 50 were from the normal population. All individuals were examined for common HFE gene mutations by amplification of nucleotide 845 C282Y and 187 H63D alleles and product analysis using the polymerase chain reaction method and restriction enzyme digestion. RESULTS: No case of either a homozygous or heterozygous C282Y mutation was found. For the H63D mutation, no homozygosity was detected but heterozygosity was detected in 22% of patients and in 28% of the normal population. CONCLUSIONS: Hereditary hemochromatosis is not a major cause of cryptogenic cirrhosis in the Iranian population. PMID- 22308153 TI - Prevalence of ATP7B Gene Mutations in Iranian Patients With Wilson Disease. AB - BACKGROUND: Wilson disease (WD) is an autosomal recessive disorder. The WD gene, ATP7B, encodes a copper-transporting ATPase involved in the transport of copper into the plasma protein ceruloplasmin and in excretion of copper from the liver. ATP7B mutations cause copper to accumulate in the liver and brain. OBJECTIVES: We examined the ATP7B mutation spectrum in Wilson disease patients in Iran. PATIENTS AND METHODS: Genomic DNA was extracted from patients with Wilson disease. The entire coding region of the ATP7B gene was amplified using PCR and analyzed using direct sequencing. RESULTS: We identified five novel mutations in 5 Iranian patients with Wilson disease. The first was a transversion, c.2363C > T, which led to an amino acid change from threonine to isoleucine. The second mutation was a deletion, c.2532delA (Val845Ser), which occurred in exon 10. The third mutation was a transition mutation, c.2311C > G (Leu770Leu), which occurred in the TM4 domain of the ATP7B protein. The fourth mutation was a transversion, (c.3061G > A) (Lys1020Lys), in exon 14. Lastly, we identified a transversion, c.3206C > A (His1069Asn) in exon 14 which led to a change in function of the ATP loop domain of the ATP7B protein. The H1069Q mutation was identified as the most common mutation in our study population. CONCLUSIONS: Based on our findings, the H1069Q may be a biomarker that can be used in a rapid detection assay for diagnosing WD patients. PMID- 22308154 TI - Hepatitis C Virus infections trends in Italy, 1996-2006. AB - BACKGROUND: The World Health Organization (WHO) estimates that about 180 million people, 3% of the world population, are infected with the hepatitis C virus (HCV). In Italy, the prevalence in the general population is reported to be greater than 5% and 9% among households of HCV-positive patients. OBJECTIVES: The aim of this study was to estimate the trends of HCV infection in Italy in the period 1996-2006. MATERIALS AND METHODS: The formula ln (rate) = b * years was applied for logarithmic transformation of the incidence rates to obtain time trends of HCV infection, using the join-point regression program software version 3.3.1. Linear graphs representing trends and the annual percentage change (APC) were considered for each joinpoint. Time changes are expressed as expected annual percentage change (EAPC) with the respective 95% confidence intervals (CIs); significance levels of time trends are also reported. The null hypothesis was tested using a maximum of 3 changes in slope with an overall significance level of 0.05 divided by the number of joinpoints in the final model. RESULTS: Considering all age groups, the incidence rate decreased from 2.02 to 0.55 per 100,000. The join-point analysis showed a statistically significant decrease in the incidence rates of HCV infection. No join-points were found in any age groups. Our data show that the incidence rates of HCV infections have considerably decreased in each age group throughout the studied period (1996 2006). CONCLUSIONS: This decreasing trend in HCV infections is, in part, attributable to behavioral and social changes. Improved hygiene, use of precautions in medical settings, blood screening, and sexual educational campaigns seem to have contributed to reduce the transmission of infection during the last 10 years. PMID- 22308155 TI - Efficacy of the confidential unit exclusion option in blood donors in tehran, iran, determined by using the nucleic Acid testing method in 2008 and 2009. AB - BACKGROUND: In recent years, the confidential unit exclusion (CUE) option has been used to increase blood safety at blood transfusion centers in several countries. The epidemiologic characteristics of diseases and demographic characteristics of patients vary in different countries; therefore, we investigated whether the CUE option is useful in Iran. In this study, we determined the prevalences of hepatitis B virus (HBV) and hepatitis C virus (HCV) in CUE-positive and CUE-negative units, as well as the efficacy of the CUE option. OBJECTIVES: The aim of this study was to evaluate the efficacy of the CUE option in reducing the prevalences of HBV and HCV in blood units. PATIENTS AND METHODS: All donors were tested for the HCV antibody (anti-HCV) and hepatitis B surface antigen (HBsAg). Supplemental tests were performed to confirm the presence of viruses in the units that tested positive. In total, 2000 units (1000 CUE-positive units and 1000 CUE-negative units) were tested using the nucleic acid testing (NAT) method. The prevalence of infectious markers was estimated in all demographic subgroups. RESULTS: The prevalences of HBV and HCV markers were higher in donors who opted for CUE than in those who did not. The CUE option had low sensitivity (21.5%) and positive predictive value (PPV; 20.9%) for the markers. Most of the donors who opted for CUE for the first time were men with low levels of education. CONCLUSIONS: The CUE option has low sensitivity and PPV, and its effectiveness in reducing the transmission of infectious diseases through window-period units is minimal. The CUE process can be continued in Iran because Iran is geographically located in a region where HBV is endemic; however, higher levels of education are necessary to make this process effective. PMID- 22308156 TI - HEV-Capsid Protein Interacts With Cytochrome P4502C8 and Retinol-Binding Protein 4. AB - BACKGROUND: Hepatitis E virus (HEV) is a major causative agent of acute clinical hepatitis in adults throughout much of Asia, the Middle East, and Africa. The lack of an efficient cell culture system for HEV has greatly limited our understanding of the mechanisms of infection, replication, and pathogenicity of this virus. The yeast two-hybridization system is considered to be an efficient method for determining protein-protein interactions and screening interactive proteins associated with host cells. OBJECTIVES: In order to identify the host cell proteins interacting with the HEV-capsid proteins, a fragment of the HEV capsid protein p239 (amino acids 368-606) was used as bait; human liver cDNA library was used as a source of host-cell proteins, and the screening was performed using the CytoTrap yeast two-hybrid system. MATERIALS AND METHODS: The CytoTrap yeast two-hybrid system, which is also called Sos Recruitment System (SRS), was used to analyze the interaction of the p239 fragment with host-cell proteins. RESULTS: We isolated 2 proteins, cytochrome P4502C8 (CYP4502C8) and retinol-binding protein 4 (RBP4) after 2 rounds of screening. Co immunoprecipitation assays showed that both the proteins could bind in vitro to the HEV virion in HepG2 cells. CONCLUSIONS: CYP4502C8 and RBP4 screened from liver cDNA library using the CytoTrap yeast two-hybrid system interact with HEV capsid in vitro. PMID- 22308157 TI - Ribavirin Impairs Salivary gland function During Combination Treatment With Pegylated Interferon Alfa-2a In HEpatitis C patients. AB - BACKGROUND: Xerostomia is a common adverse event of unknown etiology observed during pegylated interferon (PegIFN)/Ribavirin (Rbv) treatment. OBJECTIVES: To assess the frequency and mechanisms of xerostomia during PegIFN/Rbv therapy. PATIENTS AND METHODS: Thirty-one naive patients with chronic hepatitis C consecutively received PegIFN-alpha2a (180 MUg/week) plus Rbv (800-1200 mg/day). The controls were 10 patients with chronic hepatitis B who received PegIFN alpha2a (180 MUg/week). During treatment and follow-up, all patients underwent basal and masticatory stimulated sialometry,otorhinolaryngoiatric (ORL) examination, and a questionnaire survey to subjectively assess symptoms of oral dryness. RESULTS: Twenty-seven patients on PegIFN/Rbv and 4 on PegIFN (87% vs. 40%, P = 0.006) reported xerostomia. Thirty patients on PegIFN/Rbv combination therapy and 2 patients on monotherapy had ORL signs of salivary gland hypofunction (97% vs. 20%, P < 0.0001).Mean basal (A) and stimulated (B) salivary flow rates (mL/min) progressively decreased during PegIFN/Rbv treatment (A, 0.49 at baseline vs. 0.17 at the end of treatment, P < 0.0001; B, 1.24 at baseline vs. 0.53 at the end of treatment, P = 0.0004). At week 24 following PegIFN/Rbv treatment, salivary flow rates were similar to baseline (A, 0.53 at the end of follow-up vs. 0.49 at baseline; B, 1.19 at the end of follow-up vs. 1.24 at baseline). Salivary function was unaffected in monotherapy patients. CONCLUSIONS: Rbv causes salivary gland hypofunction in hepatitis C patients receiving PegIFN/Rbv therapy, which promptly reverts to normal upon cessation of treatment. PMID- 22308158 TI - Effect of ribavirin therapy on salivary gland function: an oral medicine prespective. PMID- 22308159 TI - Hepatitis e virus infection in Iranian kidney-transplant patients. PMID- 22308160 TI - Author's Reply: Hepatitis E Virus Infection in Iranian Kidney-Transplant Patients. PMID- 22308161 TI - Effect of chronic cervical ganglionectomy on the spontaneous variability of internal carotid blood flow in the conscious rat. AB - The role of sympathetic innervation in the control of spontaneous fluctuations of cerebral blood flow is still poorly understood. In conscious, unrestrained rats, blood flow velocity (pulsed Doppler) was measured in both internal carotid arteries 1 week after either excision of the right superior cervical ganglion (n = 8) or sham surgery (n = 6). Using Fourier-based techniques, spectral power of each carotid blood flow (CBF) was computed over the whole recording period (246 min), which was segmented into nine consecutive 27.3 min periods. Variability of CBF (spectral power) was ~40% higher (P < 0.02) on the denervated than on the intact side at frequencies <1 Hz. Coherence between left and right CBFs was similar in the two groups of rats, except in the 0.01-0.1 Hz frequency range where it was lower (P < 0.05) in rats with unilateral sympathectomy (0.54 +/- 0.03) than in intact rats (0.74 +/- 0.06). In this frequency range, mathematically removing the influence of arterial pressure had little effect on coherence between CBFs in both groups of rats, so that coherence remained significantly lower in rats with unilateral sympathectomy (0.52 +/- 0.03) than in intact rats (0.70 +/- 0.06). This study indicates that sympathetic innervation has an overall buffering influence on CBF variability. This modulatory role is especially important in a frequency range corresponding to slow fluctuations of CBF (lasting from 10 to 100 s), which are essentially unrelated to fluctuations of arterial pressure. PMID- 22308162 TI - AMP-activated protein kinase alpha2 is an essential signal in the regulation of insulin-stimulated fatty acid uptake in control-fed and high-fat-fed mice. AB - Owing to its critical role in the regulation of skeletal muscle metabolism, AMP activated protein kinase (AMPK) remains a central focus of research for the treatment of insulin resistance. The purpose of the present study was to determine the role of AMPKalpha2 activity in the regulation of glucose uptake and fatty acid (FA) metabolism in insulin-resistant skeletal muscle. Male C57BL/6 mice were divided into groups fed a control diet (CD) or high-fat (60%) diet (HFD) for 6 weeks and were either wild-type (WT) or possessed an AMPKalpha2 dominant negative transgene (DN). After 6 weeks, hindlimbs of CD (n = 10) and HFD mice (n = 10) were perfused with or without 450 MUU ml(-1) insulin. Muscles of CD (n = 8) and HFD mice (n = 8) were used for measurement of basal protein expression. In CD mice, low AMPKalpha2 activity did not affect basal FA uptake (FAU), but it increased basal FA oxidation (FAO) by 28% and prevented the typical insulin-mediated increase in FAU and decrease in FAO. In HFD-fed mice, low AMPKalpha2 activity increased basal FAU by 147% (P < 0.05). In both WT and DN mice, HFD abolished the typical insulin-mediated increase in FAU and decrease in FAO. In HFD-fed mice, low AMPKalpha2 activity increased SIRT1 activity and decreased Protein Tyrosine Phosphatase 1B (PTP1B) expression and Akt(Thr308) phosphorylation (P < 0.05). Adipose tissue protein expression of interleukin-6 and tumour necrosis factor alpha was increased by HFD in WT mice but not in DN mice (P < 0.05). Skeletal muscle interleukin-15 expression was decreased in both feeding conditions in the DN mice (P < 0.05). The data from this study suggest that in insulin-resistant conditions low AMPKalpha2 activity impacts the regulation of skeletal muscle FA metabolism via changes in SIRT1 activity, PTP1B expression and Akt phosphorylation and the expression of adipose tissue pro-inflammatory markers. PMID- 22308163 TI - Explosive neuromuscular performance of males versus females. AB - The purpose of the study was to investigate sex-related differences in explosive muscular force production, as measured by electromechanical delay (EMD) and rate of force development (RFD), and to examine the physiological mechanisms responsible for any differences. The neuromuscular performance of untrained males (n = 20) and females (n = 20) was assessed during a series of isometric knee extension contractions; explosive and maximal voluntary efforts, as well as supramaximal evoked twitches and octets (eight pulses at 300 Hz). Evoked and voluntary EMD were determined from twitch and explosive contractions. The RFD was recorded over consecutive 50 ms time windows from force onset during evoked and explosive contractions, and normalized to maximal strength. Neuromuscular activity during explosive voluntary contractions was measured with EMG of the superficial knee extensors normalized to maximal M-wave. Muscle size (thickness) and muscle-tendon unit (MTU) stiffness were assessed using ultrasonic images of the vastus lateralis at rest and during ramped contractions. Males and females had similar evoked and voluntary EMD. Males were 33% stronger (P < 0.001) and their absolute RFD was 26-56% greater (all time points P < 0.05) compared with females. Muscle size (P < 0.001) and absolute MTU stiffness were also greater for males (P < 0.05). However, normalized RFD was similar for both sexes during the first 150 ms of the explosive voluntary contractions (P > 0.05). This was consistent with the similar normalized twitch and octet RFD, MTU stiffness and agonist EMG (all P > 0.05). When differences in maximal strength were accounted for, the evoked capacity of the knee extensors for explosive force production and the ability to utilize that capacity during explosive voluntary contractions was similar for males and females. PMID- 22308164 TI - Short-term training for explosive strength causes neural and mechanical adaptations. AB - This study investigated the neural and peripheral adaptations to short-term training for explosive force production. Ten men trained the knee extensors with unilateral explosive isometric contractions (1 s 'fast and hard') for 4 weeks. Before and after training, force was recorded at 50-ms intervals from force onset (F(50), F(100) and F(150)) during both voluntary and involuntary (supramaximal evoked octet; eight pulses at 300 Hz) explosive isometric contractions. Neural drive during the explosive voluntary contractions was measured with the ratio of voluntary/octet force, and average EMG normalized to the peak-to-peak M-wave of the three superficial quadriceps. Maximal voluntary force (MVF) was also measured, and ultrasonic images of the vastus lateralis were recorded during ramped contractions to assess muscle-tendon unit stiffness between 50 and 90% MVF. There was an increase in voluntary F(50) (+54%), F(100) (+15%) and F(150) (+14%) and in octet F(50) (+7%) and F(100) (+10%). Voluntary F(100) and F(150), and octet F(50) and F(100) increased proportionally with MVF (+11%). However, the increase in voluntary F(50) was +37% even after normalization to MVF, and coincided with a 42% increase in both voluntary/octet force and agonist normalized EMG over the first 50 ms. Muscle-tendon unit stiffness between 50 and 90% MVF also increased. In conclusion, enhanced agonist neural drive and MVF accounted for improved explosive voluntary force production in the early and late phases of the contraction, respectively. The increases in explosive octet force and muscle-tendon unit stiffness provide novel evidence of peripheral adaptations within merely 4 weeks of training for explosive force production. PMID- 22308165 TI - Physical activity, cardio-respiratory fitness, and metabolic traits in rural Mexican Tarahumara. AB - OBJECTIVES: To study the association between physical activity energy expenditure (PAEE) and cardio-respiratory fitness (CRF) with key metabolic traits and anthropometric measures in the Tarahumara of Mexico. METHODS: A cross-sectional study was carried out in five rural communities in Chihuahua, Mexico including 64 adult Tarahumara, mean (SD) age 40.7 (12.9) years. Using a combined accelerometer and heart rate sensor, PAEE was measured over three consecutive days and nights and a sub-maximal step test was carried out in order to (1) calibrate heart rate at the individual level and (2) to estimate CRF. Random blood glucose level and resting blood pressure (BP) were measured with standard anthropometrics. RESULTS: Mean (SD) PAEE was 71.2 (30.3) kJ kg(-1) day(-1) and CRF was 36.6 (6.5) mlO(2) min(-1) kg(-1) . Mean (SD) glucose was 127.9 (32.4) mg/dl, with 3.3% having diabetes. Mean (SD) systolic and diastolic BP was 122 (20.8) and 82 (14.8) mm Hg, respectively, with 28.1% having hypertension. Mean body mass index was 27.5 (4.2) kg m(-2) , with 71.9% being overweight. Following adjustment for age and sex, weak inverse associations were observed between PAEE and systolic BP (beta = 0.20, P = 0.27) and diastolic BP (beta = -0.16, P = 0.23); and between CRF and systolic BP (beta = -0.51, P = 0.14) and diastolic BP (beta = -0.53, P = 0.06). The inverse associations with glucose were also weak and not statistically significant for neither PAEE (beta = -0.01, P = 0.63) nor CRF (beta = -0.05, P = 0.27). CONCLUSIONS: This study suggests high levels of overweight and hypertension in the Tarahumara, and points to fitness and physical activity as potential intervention targets although findings should be confirmed in larger samples. PMID- 22308166 TI - Kinetic resolution of planar-chiral (eta6-arene)chromium complexes by molybdenum catalyzed asymmetric ring-closing metathesis. PMID- 22308167 TI - One-dimensional organic photonic heterostructures: rational construction and spatial engineering of excitonic emission. AB - Organic photonic heterostructures are constructed through a template-free self assembly method. The host-guest intermolecular interactions play an essential role in the formation of various block orange-blue-orange and blue/green microtubes. The spatial distribution of excitons is engineered to investigate the excitonic behaviors in light propagation along the axial heterostructures. These results offer a new route to the integration of organic photonic building blocks for optical processing applications. PMID- 22308168 TI - Arsenic migration to deep groundwater in Bangladesh influenced by adsorption and water demand. AB - Drinking shallow groundwater with naturally elevated concentrations of arsenic is causing widespread disease in many parts of South and Southeast Asia. In the Bengal Basin, growing reliance on deep (>150 m) groundwater has lowered exposure. In the most affected districts of Bangladesh, shallow groundwater concentrations average 100 to 370 MUg L(-1), while deep groundwater is typically < 10 MUg L(-1). Groundwater flow simulations have suggested that, even when deep pumping is restricted to domestic use, deep groundwater in some areas of the Bengal Basin is at risk of contamination. However, these simulations have neglected the impedance of As migration by adsorption to aquifer sediments. Here we quantify for the first time As sorption on deeper sediments in situ by replicating the intrusion of shallow groundwater through injection of 1,000 L of deep groundwater modified with 200 MUg L(-1) of As into a deeper aquifer. Arsenic concentrations in the injected water were reduced by 70% due to adsorption within a single day. Basin scale modelling indicates that while As adsorption extends the sustainable use of deep groundwater, some areas remain vulnerable; these areas can be prioritized for management and monitoring. PMID- 22308169 TI - Radiation dose reduction in computed tomography: techniques and future perspective. AB - Despite universal consensus that computed tomography (CT) overwhelmingly benefits patients when used for appropriate indications, concerns have been raised regarding the potential risk of cancer induction from CT due to the exponentially increased use of CT in medicine. Keeping radiation dose as low as reasonably achievable, consistent with the diagnostic task, remains the most important strategy for decreasing this potential risk. This article summarizes the general technical strategies that are commonly used for radiation dose management in CT. Dose-management strategies for pediatric CT, cardiac CT, dual-energy CT, CT perfusion and interventional CT are specifically discussed, and future perspectives on CT dose reduction are presented. PMID- 22308171 TI - Enhanced resistance to bacterial and fungal pathogens by overexpression of a human cathelicidin antimicrobial peptide (hCAP18/LL-37) in Chinese cabbage. AB - The human cathelicidin antimicrobial protein hCAP18, which includes the C terminal peptide LL-37, is a multifunctional protein. As a possible approach to enhancing the resistance to plant disease, a DNA fragment coding for hCAP18/LL-37 was fused at the C-terminal end of the leader sequence of endopolygalacturonase inhibiting protein under the control of the cauliflower mosaic virus 35S promoter region. The construct was then introduced into Brassica rapa. LL-37 expression was confirmed in transgenic plants by reverse transcription-polymerase chain reaction and western blot analysis. Transgenic plants exhibited varying levels of resistance to bacterial and fungal pathogens. The average size of disease lesions in the transgenic plants was reduced to less than half of that in wild-type plants. Our results suggest that the antimicrobial LL-37 peptide is involved in wide-spectrum resistance to bacterial and fungal pathogen infection. PMID- 22308170 TI - Recent advances of metabolomics in plant biotechnology. AB - Biotechnology, including genetic modification, is a very important approach to regulate the production of particular metabolites in plants to improve their adaptation to environmental stress, to improve food quality, and to increase crop yield. Unfortunately, these approaches do not necessarily lead to the expected results due to the highly complex mechanisms underlying metabolic regulation in plants. In this context, metabolomics plays a key role in plant molecular biotechnology, where plant cells are modified by the expression of engineered genes, because we can obtain information on the metabolic status of cells via a snapshot of their metabolome. Although metabolome analysis could be used to evaluate the effect of foreign genes and understand the metabolic state of cells, there is no single analytical method for metabolomics because of the wide range of chemicals synthesized in plants. Here, we describe the basic analytical advancements in plant metabolomics and bioinformatics and the application of metabolomics to the biological study of plants. PMID- 22308172 TI - Rasch analysis of the Indian vision function questionnaire. AB - AIM: To investigate the psychometric properties of the three scales (general functioning, psychosocial impact, visual symptoms) of the Indian vision function questionnaire (IND-VFQ) using the Rasch measurement model. METHODS: 236 visually impaired patients referred to vision rehabilitation centres were administered the 33-item IND-VFQ. Rasch analysis was used to investigate the scales for the following properties: precision by person separation (ie, discrimination between strata of patient ability, recommended minimum value 2.0), unidimensionality (ie, measurement of a single construct) and targeting (ie, matching of item difficulty to patient ability). RESULTS: Only the general functioning scale possessed adequate measurement precision (person separation 3.49). However, it lacked unidimensionality as some items did not contribute towards the measurement of a single construct indicating a secondary dimension. This comprised seven mobility items, which formed a separate valid subscale with good targeting (-0.57 logits). Deleting these items restored unidimensionality but a misfitting item required removal. Following this the 13 items fit and were visual functioning related. However, targeting was suboptimal (-1.13 logits). CONCLUSIONS: The general functioning scale of the IND-VFQ consists of two separate unidimensional constructs: visual functioning and mobility. Both these Rasch scaled versions with good psychometric properties are effective tools for the assessment of visually impaired patients in India. PMID- 22308174 TI - Chiral monodentate phosphines and bulky carboxylic acids: cooperative effects in palladium-catalyzed enantioselective C(sp3)-H functionalization. PMID- 22308173 TI - On the cutting edge of proprotein convertase pharmacology: from molecular concepts to clinical applications. AB - There is increasing interest in the therapeutic targeting of proteases for the treatment of important diseases. Additionally new protein-based therapeutic strategies have the potential to widen the available treatments against these pathologies. In the last decade, accumulated evidence has confirmed that the family of proteases known as proprotein convertases (PCs) are potential targets for viral infections, osteoarthritis, cancer and cardiovascular disease, among others. Nevertheless, there are still many unanswered questions about the relevance of targeting PCs in a therapeutic context, especially regarding the anticipated secondary effects of treatment, considering the observed embryonic lethality of some PC knockout mice. In this review, the benefits of PCs as pharmacological targets will be discussed, with focus on concepts and strategies, as well as on the state of advancement of actual and future inhibitors. PMID- 22308175 TI - A pilot study to expand the school breakfast program in one middle school. AB - School Breakfast Program (SBP) eaters weigh less and have healthier diets than nonSBP eaters. However, SBP is underused nationally, especially among low income youth. To explore the feasibility of expanding access to the SBP to improve participation among sixth grade students in one middle school in Minneapolis, Minnesota. A grab-n-go SBP menu, hallway delivery service and in-classroom eating strategies were implemented and evaluated with a cohort of sixth grade students (n=239) for 6weeks during spring 2010. Process measures were collected from students and teachers and through direct observations. The school district provided objective SBP participation data at baseline and post intervention. Students were very satisfied with eating in the classrooms (64%). Teachers (n=10) rated eating in the classroom as not messy, not disruptive and student behavior as excellent or good (100%). There was a significant increase in SBP participation from 0.74days per week to 1.21days per week (p<0.0001). Improvements were more pronounced among students eligible for free and reduced priced school meals. A school environment that supports convenient SBP menu and serving and eating locations was feasible and increased SBP participation in this suburban middle school. PMID- 22308177 TI - The development of the error-related negativity (ERN) and its relationship with anxiety: evidence from 8 to 13 year-olds. AB - Because anxiety disorders appear to follow developmental trajectories that begin early in development, it may be useful to examine the neurodevelopmental correlates of specific cognitive processes that have been linked to anxiety. For instance, the error-related negativity (ERN) is a negative deflection in the event-related potential that is maximal approximately 50 ms following the commission of errors at fronto-central electrode sites,and has consistently been found to be more negative among anxious adults. Much less,however, is known about anxiety and the ERN in children-especially when this relationship develops. We recorded event-related potentials (ERPs) while 55 children aged 8-13 performed an arrow version of the flankers task. Parents and children both reported on children's anxiety. Results suggest that the relationship between the ERN and anxiety changes as a function of age. Among older children, a larger (i.e., more negative) ERN was significantly related to increased anxiety based on parent report. Although the relationship was less robust, the relationship between ERN and anxiety was opposite among younger children.These results are discussed in terms of existing work on anxiety and the ERN, and the need for longitudinal and developmental studies on the relationship between ERN andanxiety PMID- 22308176 TI - Targeting Dopamine in Acute Traumatic Brain Injury. AB - In addition to the initial mechanical damage, traumatic brain injury (TBI) induces a series of secondary insults, such as, but not limited to, excitotoxicity, metabolic disruption, and oxidative stress. Neuroprotective strategies after TBI have traditionally focused on cellular preservation as the measurable endpoint although multiple lines of evidence indicate that even with significant neuronal sparing deficits remain at both the cellular and behavioral level. As such, the development of therapies that can effectively confer both neuronal sparing and post-injury functional benefit is critical to providing the best treatment options for clinical TBI. Targeting dopaminergic signaling pathways is a novel approach in TBI that provides benefits to both neuronal survival and functional outcomes. Dopamine, like glutamate, can cause oxidative stress and significant cellular dysfunction when either depleted or over expressed, and also plays an important role in central nervous system inflammation. The purpose of this review is to discuss dopamine in acute TBI and the role that dopaminergic therapies have as neuroprotective strategies. PMID- 22308178 TI - An international comparative family medicine study of the Transition Project data from the Netherlands, Malta and Serbia. Is family medicine an international discipline? Comparing diagnostic odds ratios across populations. AB - INTRODUCTION: This is an international study of the epidemiology of family medicine (FM) in three practice populations from the Netherlands, Malta and Serbia. Diagnostic associations between common reasons for encounter (RfEs) and episodes titles are compared and similarities and differences are described and analysed. METHODOLOGY: Participating family doctors (FDs) recorded details of all their patient contacts in an 'episode of care (EoC)' structure using the International Classification of Primary Care (ICPC). RfEs presented by the patient and episode titles (diagnostic labels of EoCs) were classified with ICPC. The relationships between RfEs and episode titles were studied with Bayesian methods. RESULTS: Distributions of diagnostic odds ratios (ORs) from the three population databases are presented and compared. CONCLUSIONS: ICPC, the RfE and the EoC data model are appropriate tools to study the process of diagnosis in FM. Distributions of diagnostic associations between RfEs and episode titles in the Transition Project international populations show remarkable similarities and congruencies in the process of diagnosis from both the RfE and the episode title perspectives. The congruence of diagnostic associations between populations supports the use of such data from one population to inform diagnostic decisions in another. Differences in the magnitude of such diagnostic associations are significant, and population-specific data are therefore desirable. We propose that both an international (common) and a local (health care system specific) content of FM exist and that the empirical distributions of diagnostic associations presented in this paper are a reflection of both these effects. We also observed that the frequency of exposure to such diagnostic challenges had a strong effect on the confidence intervals of diagnostic ORs reflecting these diagnostic associations. We propose that this constitutes evidence that expertise in FM is associated with frequency of exposure to diagnostic challenges. PMID- 22308179 TI - Prioritizing areas for quality marker development in children in UK general practice: extending the use of the nominal group technique. AB - BACKGROUND: There is a deficiency in the ability to measure the quality of care of children in primary care and there is no professional consensus in UK general practice regarding which quality markers should be used. OBJECTIVES: To prioritize clinical areas on which to focus quality marker development in paediatric primary care and to describe the challenges in generating professional consensus. METHODS: We convened an expert panel of GPs with a special interest in child health and using the nominal group technique (NGT), a well-established structured, multistep facilitated group meeting technique, we generated consensus around the key clinical areas to focus quality marker development. RESULTS: Twelve GPs participated in the expert panel. The eight items agreed by panellists as most important were early recognition of serious illness, whole practice involvement in safeguarding, health promotion, mental health, evidence-based management of common conditions, child and carer friendliness and safe and cost effective prescribing. Panel members struggled to balance the broad clinical areas while attempting to focus on specific areas that are important. The main challenges included managing panel uncertainty, effective organization, presentation of items for review and group inclination to 'include everything'. CONCLUSIONS: This is the first consensus study of UK GPs to identify key areas to target quality marker development in children. By using the NGT, we have highlighted front-line health care professionals' priorities to improve the quality of care of children and identified the benefits and challenges of developing consensus in a broad topic area. PMID- 22308180 TI - An international comparative family medicine study of the Transition Project data from the Netherlands, Malta, Japan and Serbia. An analysis of diagnostic odds ratios aggregated across age bands, years of observation and individual practices. AB - INTRODUCTION: This is a study of the process of diagnosis in family medicine (FM) in four practice populations from the Netherlands, Malta, Serbia and Japan. Diagnostic odds ratios (ORs) for common reasons for encounter (RfEs) and episode titles are used to study the process of diagnosis in international FM and to test the assumption that data can be aggregated across different age bands, practices and years of observation. METHODOLOGY: Participating family doctors (FDs) recorded details of all their patient contacts in an episode of care (EoC) structure using the International Classification of Primary Care (ICPC). RfEs presented by the patient and the diagnostic labels (EoC titles) recorded for each encounter were classified with ICPC. The relationships between RfEs and episode titles were expressed as ORs using Bayesian probability analysis to calculate the posterior (post-test) odds of an episode title given an RfE, at the start of a new EoC. RESULTS: The distributions of diagnostic ORs from the four population databases are tabled across age groups, years of observation and practices. CONCLUSIONS: There is a lot of congruence in diagnostic process and concepts between populations, across age groups, years of observation and FD practices, despite differences in the strength of such diagnostic associations. There is particularly little variability of diagnostic ORs across years of observation and between individual FD practices. Given our findings, it makes sense to aggregate diagnostic data from different FD practices and years of observation. Our findings support the existence of common core diagnostic concepts in international FM. PMID- 22308181 TI - Reasons for encounter and symptom diagnoses: a superior description of patients' problems in contrast to medically unexplained symptoms (MUS). AB - This is a review of the literature on the role of symptoms in family practice, with a focus on the diagnostic approach in family medicine (FM). We found two, contrasting, approaches to reducing symptoms presented by patients in primary care, especially those which do not immediately allow the definition of a disease label diagnosis. Years of research into 'medically unexplained symptoms' (MUS) has failed to support an international body of knowledge and cannot convincingly support the philosophy on which the reduction itself is based. This review supports the approach of researching reasons for encounter as they present to the family doctor, without artificial mind-body metaphors. The medical model is shown to be an incomplete reduction of FM, and the concept of MUS fails to improve this situation. A new model based on a substantial paradigm shift is needed. That model should be the biopsychosocial model, reflected in the philosophical concepts of the International Classification of Primary Care and the value of the patient's 'reason for encounter'. There is more to life than medicine may diagnose, and FM should strive to move closer to the lives of our patients than the medical model alone could allow. PMID- 22308182 TI - An international comparative family medicine study of the Transition Project data from the Netherlands, Malta and Serbia. Is family medicine an international discipline? Comparing incidence and prevalence rates of reasons for encounter and diagnostic titles of episodes of care across populations. AB - INTRODUCTION: This is a study of the epidemiology of family medicine (FM) in three practice populations from the Netherlands, Malta and Serbia. Incidence and prevalence rates, especially of reasons for encounter (RfEs) and episode labels, are compared. METHODOLOGY: Participating family doctors (FDs) recorded details of all their patient contacts in an episode of care (EoC) structure using electronic patient records based on the International Classification of Primary Care (ICPC), collecting data on all elements of the doctor-patient encounter. RfEs presented by the patient, all FD interventions and the diagnostic labels (EoCs labels) recorded for each encounter were classified with ICPC (ICPC-2-E in Malta and Serbia and ICPC-1 in the Netherlands). RESULTS: The content of family practice in the three population databases, incidence and prevalence rates of the common top 20 RfEs and EoCs in the three databases are given. CONCLUSIONS: Data that are collected with an episode-based model define incidence and prevalence rates much more precisely. Incidence and prevalence rates reflect the content of the doctor patient encounter in FM but only from a superficial perspective. However, we found evidence of an international FM core content and a local FM content reflected by important similarities in such distributions. FM is a complex discipline, and the reduction of the content of a consultation into one or more medical diagnoses, ignoring the patient's RfE, is a coarse reduction, which lacks power to fully characterize a population's health care needs. In fact, RfE distributions seem to be more consistent between populations than distributions of EoCs are, in many respects. PMID- 22308189 TI - Potential roles of microsomal prostaglandin E synthase-1 in rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a chronic autoimmune disease which primarily affects the synovial joints leading to inflammation, pain and joint deformities. Nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, both of which inhibit cyclooxygenase (COX), have been extensively used for treating RA patients. Prostaglandin E synthase (PGES) is a specific biosynthetic enzyme that acts downstream of COX and converts prostaglandin (PG) H(2) to PGE(2). Among PGES isozymes, microsomal PGES-1 (mPGES-1) has been shown to be induced in a variety of cells and tissues under inflammatory conditions. The induction of mPGES-1 in the synovial tissue of RA patients is closely associated with the activation of the tissue by proinflammatory cytokines. Although selective mPGES-1 inhibitors have not yet been widely available, mice lacking mPGES-1 (mPGES-1(-/-) mice) have been generated to evaluate the physiological and pathological roles of mPGES-1 in vivo. Recent studies utilizing mPGES-1(-/-) mice have demonstrated the significance of mPGES-1 in the process of chronic inflammation and evocation of humoral immune response in autoimmune arthritis models. These recent findings highlight mPGES-1 as a novel therapeutic target for the treatment of autoimmune inflammatory diseases, including RA. Currently, both natural and synthetic chemicals are being tested for inhibition of mPGES-1 activity to produce PGE(2). The present review focuses on the recent advances in understanding the role of mPGES-1 in the pathophysiology of RA. PMID- 22308190 TI - THE POTENTIAL FOR BIAS IN PRINCIPAL CAUSAL EFFECT ESTIMATION WHEN TREATMENT RECEIVED DEPENDS ON A KEY COVARIATE. AB - Motivated by a potential-outcomes perspective, the idea of principal stratification has been widely recognized for its relevance in settings susceptible to posttreatment selection bias such as randomized clinical trials where treatment received can differ from treatment assigned. In one such setting, we address subtleties involved in inference for causal effects when using a key covariate to predict membership in latent principal strata. We show that when treatment received can differ from treatment assigned in both study arms, incorporating a stratum-predictive covariate can make estimates of the "complier average causal effect" (CACE) derive from observations in the two treatment arms with different covariate distributions. Adopting a Bayesian perspective and using Markov chain Monte Carlo for computation, we develop posterior checks that characterize the extent to which incorporating the pretreatment covariate endangers estimation of the CACE. We apply the method to analyze a clinical trial comparing two treatments for jaw fractures in which the study protocol allowed surgeons to overrule both possible randomized treatment assignments based on their clinical judgment and the data contained a key covariate (injury severity) predictive of treatment received. PMID- 22308191 TI - ToF-SIMS Analysis of Adsorbed Proteins: Principal Component Analysis of the Primary Ion Species Effect on the Protein Fragmentation Patterns. AB - In time-of-flight secondary ion mass spectrometry (ToF-SIMS), the choice of primary ion used for analysis can influence the resulting mass spectrum. This is because different primary ion types can produce different fragmentation pathways. In this study, analysis of single-component protein monolayers were performed using monatomic, tri-atomic, and polyatomic primary ion sources. Eight primary ions (Cs(+), Au(+), Au(3) (+), Bi(+), Bi(3) (+), Bi(3) (++), C(60) (+)) were used to examine to the low mass (m/z < 200) fragmentation patterns from five different proteins (bovine serum albumin, bovine serum fibrinogen, bovine immunoglobulin G and chicken egg white lysozyme) adsorbed onto mica surfaces. Principal component analysis (PCA) processing of the ToF-SIMS data showed that variation in peak intensity caused by the primary ions was greater than differences in protein composition. The spectra generated by Cs(+), Au(+) and Bi(+) primary ions were similar, but the spectra generated by monatomic, tri-atomic and polyatomic primary ion ions varied significantly. C(60) primary ions increased fragmentation of the adsorbed proteins in the m/z < 200 region, resulting in more intense low m/z peaks. Thus, comparison of data obtained by one primary ion species with that obtained by another primary ion species should be done with caution. However, for the spectra generated using a given primary ion beam, discrimination between the spectra of different proteins followed similar trends. Therefore, a PCA model of proteins created with a given ion source should only be applied to datasets obtained using the same ion source. The type of information obtained from PCA depended on the peak set used. When only amino acid peaks were used, PCA was able to identify the relationship between proteins by their amino acid composition. When all peaks from m/z 12-200 were used, PCA separated proteins based on a ratio of C(4)H(8)N(+) to K(+) peak intensities. This ratio correlated with the thickness of the protein films and Bi(1) (+) primary ions produced the most surface sensitive spectra. PMID- 22308192 TI - Controlling Population Structure in Human Genetic Association Studies with Samples of Unrelated Individuals. AB - In genetic studies, associations between genotypes and phenotypes may be confounded by unrecognized population structure and/or admixture. Studies have shown that even in European populations, which are thought to be relatively homogeneous, population stratification exists and can affect the validity of association studies. A number of methods have been proposed to address this issue in recent years. Among them, the mixed-model based approach and the principal component-based approach have several advantages over other methods. However, these approaches have not been thoroughly evaluated on large human datasets. The objectives of this study are to (1) evaluate and compare the performance of the mixed-model approach and the principal component-based approach for genetic association mapping using human data consisting of unrelated individuals, and (2) understand the relationship between these two approaches. To achieve these goals, we simulate datasets based on the HapMap data under various scenarios. Our results indicate that the mixed-model approach performs well in controlling for population structure/admixture. It has similar performance as that based on principal component analysis. However, the approach combining mixed-model and principal component analysis does not perform as well as either method itself. PMID- 22308193 TI - Practical Consideration of Genotype Imputation: Sample Size, Window Size, Reference Choice, and Untyped Rate. AB - Imputation offers a promising way to infer the missing and/or untyped genotypes in genetic studies. In practice, however, many factors may affect the quality of imputation. In this study, we evaluated the influence of untyped rate, sizes of the study sample and the reference sample, window size, and reference choice (for admixed population), as the factors affecting the quality of imputation. The results show that in order to obtain good imputation quality, it is necessary to have an untyped rate less than 50%, a reference sample size greater than 50, and a window size of greater than 500 SNPs (roughly 1 MB in base pairs). Compared with the whole-region imputation, piecewise imputation with large-enough window sizes provides improved efficacy. For an admixed study sample, if only an external reference panel is used, it should include samples from the ancestral populations that represent the admixed population under investigation. Internal references are strongly recommended. When internal references are limited, however, augmentation by external references should be used carefully. More specifically, augmentation with samples from the major source populations of the admixture can lower the quality of imputation; augmentation with seemingly genetically unrelated cohorts may improve the quality of imputation. PMID- 22308194 TI - Allometric Prediction of Energy Expenditure in Infants and Children. AB - Predicting energy needs in children is complicated by the wide range of patient sizes, confusing traditional estimation equations, nonobjective stress-activity factors, and so on. These complications promote errors in bedside estimates of nutritional needs by rendering the estimation methods functionally unavailable to bedside clinicians. Here, the authors develop a simple heuristic energy prediction equation that requires only body mass (not height, age, or sex) as input. Expert estimation of energy expenditure suggested a power-law relationship between mass and energy. A similar mass-energy expenditure relationship was derived from published pediatric echocardiographic data using a Monte Carlo model of energy expenditure based on oxygen delivery and consumption. A simplified form of the equation was compared with energy required for normal growth in a cohort of historical patients weighing 2 to 70 kg. All 3 methods demonstrate that variation in energy expenditure in children is dominated by mass and can be estimated by the following equation: Power(kcal/kg/d) = 200 * [Mass(kg)((-0.4))]. This relationship explains 85% of the variability in energy required to maintain expected growth over a broad range of surgical clinical contexts. A simplified power-law equation predicts real-world energy needs for growth in patients over a wide range of body sizes and clinical contexts, providing a more useful bedside tool than traditional estimators. PMID- 22308195 TI - Regulator of G-protein signaling 18 controls megakaryopoiesis and the cilia mediated vertebrate mechanosensory system. AB - RGS18 was originally identified as a R4 subfamily member of regulators of G protein signaling (RGS) with specific expression in hematopoietic progenitors, myeloerythroid cells, and megakaryocytes, though its physiological role in hematopoiesis remained unknown. Here, we show that lentiviral RGS18 overexpression during differentiation of mouse Sca1(+) hematopoietic stem cells induced a 50% increase of megakaryocyte proliferation. RGS18 depletion in zebrafish results in thrombocytopenia, as 66 to 88% of the embryos lack thrombocytes after injection of an ATG or splice-blocking morpholino, respectively. These embryos have no defects in early hematopoiesis, erythropoiesis, or leukocyte number and migration. In addition, all RGS18 depleted embryos have curly tails and an almost absent response to acoustic stimuli. In situ hybridization in zebrafish, Xenopus, and mouse embryos shows RGS18 expression in thrombocytes and/or hematological tissues but also in brain and otic vesicles. RGS18 interferes with development of cilia in hair cells of the inner ear and neuromast cells. On the basis of literature evidence that RGS R4 members interact with the G-protein-modulated Wnt/calcium pathway, Wnt5b- but not Wnt5a-depleted embryos phenocopy all RGS18 knockdown effects. In summary, our study is the first to show that RGS18 regulates megakaryopoiesis but also reveals its unexpected role in ciliogenesis, at least in lower vertebrates, via interference with Wnt signaling. PMID- 22308196 TI - Aberrant action of amyloidogenic host defense peptides: a new paradigm to investigate neurodegenerative disorders? AB - Host defense peptides (HDPs) are components of the innate immune system with activity against a broad range of microbes. In some cases, it appears that this activity is mediated by the ability of these peptides to permeabilize microbial membranes via the formation of amyloid associated structures. Recent evidence suggests that the naturally occurring function of the Abeta40 and Abeta42 peptides, which are causative agents of Alzheimer's disease, may be to serve as amyloidogenic HDPs. Here, it is hypothesized that the neurotoxicity of these peptides is related to aberrant use of their amyloid-mediated antimicrobial mechanisms, which provides the as yet unexplored paradigm of a relationship among HDPs, neurodegenerative disorders, and other conditions that could contribute to their understanding and remediation. PMID- 22308197 TI - Adolescent nicotine exposure transiently increases high-affinity nicotinic receptors and modulates inhibitory synaptic transmission in rat medial prefrontal cortex. AB - Adolescence is a critical developmental period during which most adult smokers initiate their habit. Adolescents are more vulnerable than adults to nicotine's long-term effects on addictive and cognitive behavior. We investigated whether adolescent nicotine exposure in rats modifies expression of nicotinic acetylcholine receptors (nAChRs) in medial prefrontal cortex (mPFC) in the short and/or long term, and whether this has functional consequences. Using receptor binding studies followed by immunoprecipitation of nAChR subunits, we showed that adolescent nicotine exposure, as compared with saline, caused an increase in mPFC nAChRs containing alpha4 or beta2 subunits (24 and 18%, respectively) 24 h after the last injection. Nicotine exposure in adulthood had no such effect. This increase was transient and was not observed 5 wk following either adolescent or adult nicotine exposure. In line with increased nAChRs expression 1 d after adolescent nicotine exposure, we observed a 34% increase in amplitude of nicotine induced spontaneous inhibitory postsynaptic currents in layer II/III mPFC pyramidal neurons. These effects were transient and specific, and observed only acutely after adolescent nicotine exposure, but not after 5 wk, and no changes were observed in adult-exposed animals. The acute nicotine-induced increase in alpha4beta2-containing receptors in adolescents interferes with the normal developmental decrease (37%) of these receptors from early adolescence (postnatal day 34) to adulthood (postnatal day 104) in the mPFC. Together, this suggests that these receptors play a role in mediating the acute rewarding effects of nicotine and may underlie the increased sensitivity of adolescents to nicotine. PMID- 22308198 TI - Prime time for transgenerational defense. PMID- 22308199 TI - Nanomedical Theranostics in Cardiovascular Disease. AB - Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. New diagnostic and therapeutic strategies are needed to mitigate this public health issue. Advances in nanotechnology have generated innovative strategies for diagnosis and therapy in a variety of diseases, foremost in cancer. Based on these studies, a novel concept referred to as nanomedical theranostics, or the combinatory application of nanoparticulate agents to allow diagnostic therapy, is being explored to enable image-guided, personalized, or targeted treatment. Preclinically, theranostics have been gradually applied to CVD with several interesting and encouraging findings. This article summarizes studies and challenges of nanotheranostic strategies in CVD. It also evaluates nanotheranostic strategies that may potentially be utilized to benefit patients. PMID- 22308200 TI - Molecular MRI of Inflammation in Atherosclerosis. AB - Inflammatory activity in atherosclerotic plaque is a risk factor for plaque rupture and atherothrombosis and may direct interventional therapy. Inflammatory activity can be evaluated at the (sub)cellular level using in vivo molecular MRI. This paper reviews recent progress in contrast-enhanced molecular MRI to visualize atherosclerotic plaque inflammation. Various MRI contrast agents, among others ultra-small particles of iron oxide, low-molecular-weight Gd-chelates, micelles, liposomes, and perfluorocarbon emulsions, have been used for in vivo visualization of various inflammation-related targets, such as macrophages, oxidized LDL, endothelial cell expression, plaque neovasculature, MMPs, apoptosis, and activated platelets/thrombus. An enzyme-activatable magnetic resonance contrast agent has been developed to study myeloperoxidase activity in inflamed plaques. Agents creating contrast based on the chemical exchange saturation transfer mechanism were used for thrombus imaging. Transfer of these molecular MRI techniques to the clinic will critically depend on the safety profiles of these newly developed magnetic resonance contrast agents. PMID- 22308201 TI - Trauma and PTSD Symptoms: Does Spiritual Struggle Mediate the Link? AB - Because exposure to potentially traumatic events is common (Kessler, Sonnega, Bromet, & Hughes, 1995), the mechanisms through which post-traumatic stress disorder (PTSD) symptoms develop is a critical area of investigation (Ozer, Best, Lipsey, & Weiss, 2003). Among the mechanisms that may predict PTSD symptoms is spiritual struggle, a set of negative religious cognitions related to understanding or responding to stressful events. Although prominent theories emphasize cognitive factors in the development and maintenance of PTSD symptoms, they have not explicitly addressed spiritual struggle. The present prospective study tested the role of spiritual struggle in the development and maintenance of PTSD symptoms following trauma. We assessed exposure to trauma and non-trauma events during the first year of college, spiritual struggle due to the most stressful event, and PTSD symptoms resulting from the index event. Spiritual struggle partially mediated the relationship between trauma and PTSD symptoms. Interestingly, some individual subscales of spiritual struggle (specifically, Punishing God Reappraisal, Reappraisal of God's Powers, and Spiritual Discontent) partially mediated the relationship between trauma and PTSD symptoms; however, reappraisal of the event to evil forces did not relate to PTSD symptoms. These results suggest that spiritual struggle is an important cognitive mechanism for many trauma victims and may have relevance for cognitive therapy for PTSD. PMID- 22308202 TI - Neopterin, a Marker of Interferon-Gamma-Inducible Inflammation, Correlates with Pyridoxal-5'-Phosphate, Waist Circumference, HDL-Cholesterol, Insulin Resistance and Mortality Risk in Adult Boston Community Dwellers of Puerto Rican Origin. AB - Interferon-gamma (IFNG), a pro-inflammatory cytokine, increases concentrations of neopterin, a stable pteridine derivative, due to IFNG-induced transcriptional activation of the rate-limiting enzyme of pteridines biosynthesis. Neopterin concentrations were reported to correlate with metabolic syndrome (MetS), the cause of increased mortality risk, in subjects of European ancestry. We were interested to assessed neopterin correlations with clinical markers of MetS and mortality risk in population with a different genetic background, i.e., Puerto Ricans residents of Boston. Since inflammation is associated with pyridoxal-5' phosphate (PLP) deficiency, we assessed correlations of neopterin with PLP. Plasma neopterin concentrations were evaluated in 592 adult (45-75 years of age) participants of Boston Puerto Rican Health Study. Neopterin concentrations correlated with abdominal obesity (waist circumference, r = 0.085, p < 0.038), HDL cholesterol (r = -0.15, p < 0.0001), insulin resistance (HOMA-IR, r = 0.08, P < 0.03), and plasma pyridoxal-5'-phosphate (PLP (r = -0.13, P = 0.002). Neopterin concentrations of >16 nmol/L at baseline were associated with the increased risk of mortality in 113 subjects followed for 6 years. The present results together with previously reported data in European subjects suggest a similar pattern of neopterin correlations with MetS and mortality risk in population with different genetic backgrounds. PLP is a cofactor of IFNG-induced key enzymes of tryptophan kynurenine metabolism. Since PLP deficiency is associated with the increased production of diabetogenic kynurenine derivative, xanthurenic acid, our results suggest that up-regulated IFNG production might contribute to the development of insulin resistance. Assessment of neopterin concentrations might help to monitor the activity of IFNG-inducible inflammation associated with aging-associated medical and psychiatric disorders. PMID- 22308203 TI - Analysis of Fluorescent Proteins with a Nanoparticle Probe. AB - This letter presents the first application of high energy, single nanoparticle probes (e.g., 520 keV Au(400) 2nm NP) in the characterization of surfaces containing fluorescent proteins (e.g., GFP variants) by their co-emitted photon, electron and secondary ion signals. NP induced protein luminescence increases with the NP incident energy, is originated by the NP impact and is transferred to the protein fluorophor via electronic energy transfer. Multi-electron emission is observed per single NP impacts and their distributions are specific to the target morphology and composition. Fragment ions of protein sub-units consisting of 2-7 amino acid peptides are observed under individual NP impacts that can be correlated to the random protein orientation relative to the impact site (e.g., outer layer or "skin" of the protein). PMID- 22308204 TI - Drosophila Dopamine2-like receptors function as autoreceptors. AB - Dopaminergic signaling pathways are conserved between mammals and Drosophila and D2 receptors have been identified in Drosophila. However, it has not been demonstrated whether Drosophila D2 receptors function as autoreceptors and regulate the release of dopamine. The goal of this study was to determine if Drosophila D2 receptors act as autoreceptors by probing the extent to which D2 agonists and antagonists affect evoked dopamine release. Fast-scan cyclic voltammetry was used to measure stimulated dopamine release at a carbon-fiber microelectrode implanted in an intact, larval Drosophila nervous system. Dopamine release was evoked using 5-second blue light stimulations that open Channelrhodopsin-2, a blue light activated cation channel that was specifically expressed in dopaminergic neurons. In mammals, administration of a D2 agonist decreases evoked dopamine release by increasing autoreceptor feedback. Similarly, we found that the D2 agonists bromocriptine and quinpirole decreased stimulated dopamine release in Drosophila. D2 antagonists were expected to increase dopamine release and the D2 antagonists flupenthixol, butaclamol, and haloperidol did increase stimulated release. Agonists did not significantly modulate dopamine uptake although the modulatory effects of D2 drugs on release were affected by prior administration of the uptake inhibitor nisoxetine. These results demonstrate that the D2 receptor functions as an autoreceptor in Drosophila. The similarities in dopamine regulation validate Drosophila as a model system for studying the basic neurobiology of dopaminergic signaling. PMID- 22308205 TI - Turnaround time and timeliness of physician interpretation in the vascular laboratory. AB - The overall turnaround time (TAT) and the physician interpretation interval (PII) for vascular laboratory (VL) tests are not often reported in the literature. OBJECTIVE: To audit the TAT and PI on weekdays (WDs) and weekends/holidays (WE). METHODS: The first available wait time (WT), the type of test, and the PII for weekday versus weekends/holidays for all patients was noted. RESULTS: The mean WT for inpatients between order and performance of the VL test was 12.48 and 9.81 hours for WD, respectively. The mean PII was 3.23 hours. There was a significant difference in PII between WD (mean 2.30 hours) and WE (16.60 hours; P < .0001). Ninety-nine percent of tests on WD were read within 24 hours compared to 76.5% on WE (P < .0001). CONCLUSIONS: Process improvement of the TAT should lead to better customer satisfaction, improve access to test results, and be a part of quality assurance in the VL. PMID- 22308206 TI - Midterm results following endovascular repair of blunt thoracic aortic injuries. AB - OBJECTIVE: Previous studies have focused on early outcomes of thoracic endovascular repair (TEVAR) of blunt thoracic aortic injuries (BTAIs). Late results remain ill-defined. The purpose of this study is to review the midterm results of our experience with endovascular repair of BTAIs. METHODS: A retrospective analysis was performed reviewing all endovascular repairs of BTAIs from 2002 to present. Preoperative, operative, and postoperative variables were recorded. Clinical end points included aortic-related mortality, stroke and paraplegia, hospital length of stay, procedure-related complications, endoleaks, and reinterventions. Computed tomography data sets were postprocessed for assessing integrity of stent grafts and late complications. RESULTS: A total of 24 cases of BTAIs treated with TEVAR were identified. Thoracic endovascular repair was successful in treating BTAIs in all patients and there were no instances of procedure-related death, stroke, or paraplegia. One access complication occurred, requiring an iliofemoral bypass. Actuarial survival estimates and freedom from reintervention at 5 years were 88.7% and 95.8%, respectively. No late endoleaks, stent fractures, or device migration were identified. One patient required a secondary intervention 1 year following the initial repair to treat a pseudocoarctation syndrome caused by a diaphragm at the distal half of the stented aorta. This was treated successfully with repeated endografting. CONCLUSIONS: Thoracic endovascular repair for BTAIs can be performed safely with low periprocedural mortality and morbidity. Midterm follow up data presented in this report further support the therapeutic role of endoluminal approach for treating BTAIs in anatomically suitable patients. PMID- 22308207 TI - A new off-pump hybrid open and endovascular repair to treat ductus Botalli and ascendens aneurysms. AB - To report a combined ascending aorta and aortic arch hybrid repair, we performed off-pump with no aortic graft replacement. A 65-year-old man, developing progressive recurrent laryngeal nerve paralysis, underwent a computed tomography (CT) angiography detecting nonpatent residual ductus Botalli aneurysm and ascending aorta aneurysm. Due to severe multimorbidities, a less-invasive alternative was elaborated. In a first step, appropriate proximal landing zone for aortic stent grafting was achieved by ascending aorta diameter reduction, with epiaortic wrapping, and debranching the supra-aortic trunks. In the second step, endovascular stent grafts were deployed from proximal ascending aorta to descending aorta, excluding the ductus Botalli aneurysm. Six-month follow-up CT shows ductus Botalli aneurysm exclusion, stable stent graft position, and ascending diameter and patent and stenosis-free supra-aortic grafts. This case supports this alternative treatment to open aortic repair under circulatory arrest and deep hypothermia, especially in those patients considered unfit for such invasive treatment. PMID- 22308208 TI - Qualitative impact of the endovascular era on vascular surgeons' comfort level and enjoyment with open and endovascular AAA repairs. AB - OBJECTIVE: To evaluate the qualitative impact of training in the endovascular era (post-2000) on vascular surgeons' comfort level and enjoyment with abdominal aortic aneurysm (AAA) repairs. METHODS: A sample of vascular surgeons (n = 1754) were sent a survey pertaining to their fellowship training and practice of AAA repair. The influence of training- and practice-related variables on qualitative outcomes was assessed. RESULTS: A total of 382 (22%) surgeons completed the survey. Surgeons who performed more endovascular aneurysm repairs (EVARs) than open AAA repairs were more likely to enjoy EVAR (P < .001). Those completing fellowship after 2000 reported a higher level of procedure-related comfort with EVAR (P = .001) compared to those completing fellowship before 2000. Conversely, surgeons completing fellowship before 2000 reported a higher level of procedure related comfort with open AAA repair (P = .001). CONCLUSION: The advent of EVAR has changed fellowship training of AAA repair and has translated into changes in both practice patterns and comfort level. PMID- 22308209 TI - Investigation and treatment of a complicated inflammatory aortoiliac aneurysm. AB - Inflammatory abdominal aortic aneurysms (IAAAs) account for 5% to 10% of all abdominal aortic aneurysms, occurring primarily in males. Their true etiology is unknown. Symptoms and signs of IAAA are so variable that they present to a wide range of specialties. There is debate in the literature whether IAAA is a manifestation of systemic autoimmune disease. We describe the case of a young female patient with complicated inflammatory aortoiliac aneurysmal disease, illustrating diagnostic and treatment challenges that remain. Our patient had a positive autoantibody screen, raised erythrocyte sedimentation rate, positive enzyme-linked immunosorbent spot test, and saccular aneurysms, including infective and inflammatory etiologies in her differential diagnosis. Early diagnosis is crucial to limit disease progression, morbidity, and mortality. Medical management is important to address the underlying disease process, but a combination of endovascular and open surgical intervention is often necessary for definitive treatment. Available evidence offers plausibility for benefit of endovascular intervention over open repair. PMID- 22308210 TI - Use of an Amplatzer vascular plug II for aortic sac occlusion after failed surgical ligation. AB - PURPOSE: To present a case of aortic sac occlusion using an Amplatzer vascular plug II (AVP). CASE REPORT: A patient with sigmoid malignancy and an infrarenal aortic aneurysm ultimately required an axillobifemoral graft for acute limb ischemia. The sac was ligated at subsequent laparotomy. Persistent filling of the sac was seen post surgery, and the sac was successfully occluded with placement of an AVP in the neck of the sac in conjunction with coil embolization of lumbar arteries. Sac occlusion was confirmed at follow-up CT. CONCLUSION: The AVP was successfully used to occlude an aortic sac after failed surgical ligation, another novel indication for this versatile embolic device. PMID- 22308211 TI - Supraclavicular scalenectomy for thoracic outlet syndrome--functional outcomes assessed using the DASH scoring system. AB - INTRODUCTION: To evaluate supraclavicular scalenectomy +/- cervical rib excision for thoracic outlet syndrome (TOS), employing Disability of Arm, Shoulder, and Hand (DASH) scoring for functional assessment post-decompression. METHODS: A QuickDASH score was calculated for each patient using the algorithm: ([sum of responses/n] - 1) * 25, where n = number of completed responses. Nonparametric analysis was employed, with significance defined as P <= .05. RESULTS: Twenty-one patients were treated for TOS by the same surgeon; with 5 bilateral procedures (total = 26 procedures). Median DASH scores pre- and postoperatively were 68.5 and 36.0, respectively (P = .002). Just one reported worsening of symptoms postoperatively. Antecedent trauma and smoking were inversely associated with DASH score postoperatively (P = .005 and P = .005). Postoperative scores were less for patients with vascular symptoms (P = .011); scores did not change significantly for those with neurologic (P = .066) or mixed symptoms (P = .345). CONCLUSIONS: This study reconfirmed the value of supraclavicular approach for TOS, with the vast majority reporting subjective improvement. PMID- 22308212 TI - The use of antithrombotic therapies in reducing synthetic small-diameter vascular graft thrombosis. AB - BACKGROUND: Thrombosis of synthetic small-diameter bypass grafts remains a major problem. The aim of this article is to review the antithrombotic strategies that have been used in an attempt to reduce graft thrombogenicity. METHODS: A PubMed/MEDLINE search was performed using the search terms "vascular graft thrombosis," "small-diameter graft thrombosis," "synthetic graft thrombosis" combined with "antithrombotic," "antiplatelet," "anticoagulant," "Dacron," "PTFE," and "polyurethane." RESULTS: The majority of studies on antithrombotic therapies have used either in vitro models or in vivo animal experiments. Many of the therapies used in these settings do show antithrombotic efficacy against synthetic graft materials. There is however, a distinct lack of human in vivo studies to further delineate the performance and limitations of therapies displaying good antithrombotic characteristics. CONCLUSION: Very few antithrombotic therapies have translated into clinical use. More human in vivo studies are required to assess the efficacy and safety of such therapies. PMID- 22308213 TI - Aortic penetration by temporary inferior vena cava filters: report of an interesting case and review of the literature. AB - We report a patient who received a retrievable G2 filter and developed inferior vena cava perforations in multiple locations, including penetration of one of the prongs inside the aortic lumen. Furthermore, we conducted an extensive literature review of similar cases to describe the clinical presentation, aortic pathology, radiologic findings, treatment, and outcomes related to this complication. PMID- 22308214 TI - Varying presentations in patients with symptomatic type IV vascular Ehlers-Danlos syndrome. AB - Ehlers-Danlos syndrome (EDS) represents a group of inheritable connective tissue disorders. Patients with type IV or vascular EDS, autosomal dominant pattern of inheritance, may present with aneurysm formation or arterial dissection. Due to vessel fragility, operative therapy for such disorders has been reserved for compelling indications in which benefit clearly warrants risk, yet assessment of risk is largely clinical with operative decisions guided by factors such as response to previous operations and age at onset of index vascular complications. We present 2 patients with differences in their clinical presentations and outcomes and review the literature with emphasis on operative decision making. PMID- 22308215 TI - Malposition of a central venous catheter into the right internal mammary vein: review of complications of catheter misplacement. AB - Central venous catheters are commonly utilized to gain vascular access for varied clinical indications. Successful catheter placement requires not only technical expertise but also awareness of the potential complications. In this article, we report a malposition of a central venous catheter in a hemodialysis patient. We review the complications of this catheter misplacement, as well as complications resulting from other central venous catheter malpositions. PMID- 22308216 TI - Syntheses and properties of trimethylaminophenoxy-substituted Zn((II)) phthalocyanines. AB - The syntheses, photophysical properties and in vitro biological behavior of a series of nine Zn((II))-phthalocyanines (ZnPcs) bearing one to eight positively charged trimethylaminophenoxy groups are reported. All ZnPcs are highly soluble in polar organic solvents, and show fluorescence and singlet oxygen quantum yields in the ranges 0.11-0.21 and 0.16-0.47, respectively. The cytotoxicity of the ZnPcs depends on both the number of charges and their site of substitution (alpha vs. beta) on the Pc isoindole units; the most promising for PDT application are the alpha-substituted di-cationic ZnPcs 6a and 17a. PMID- 22308217 TI - A general approach to the enantioselective alpha-oxidation of aldehydes via synergistic catalysis. AB - A new enantioselective alpha-oxidation of aldehydes has been accomplished using TEMPO and a synergistic combination of copper and organic catalysis. Expanding upon recently reported mechanistic studies, these mild catalytic conditions provide stable aldehyde products bearing a wide array of electronically and sterically diverse substructures. The utility of these oxidized products is highlighted by subsequent derivatization to a variety of common chiral synthons, without loss in enantiopurity. PMID- 22308218 TI - Overweight status and intrauterine exposure to gestational diabetes are associated with children's metabolic health. AB - BACKGROUND: Offspring of women with gestational diabetes (OGD) have greater risk for obesity and impaired metabolic health. Whether impaired metabolic health occurs in the absence of obesity is not clear. OBJECTIVE: The purpose of this study was to investigate the independent and interactive effects of intrauterine exposure to gestational diabetes and of children's current weight status on their metabolic health. METHODS: Children aged 5-10 years (n = 51) with and without intrauterine exposure to gestational diabetes (OGD vs. offspring of non-diabetic women [CTRL]) were grouped into normal weight (body mass index [BMI] < 85th %) and overweight (BMI > 85th %) according to Centers for Disease Control growth curves. Lipid profile was obtained by fasting blood draw, insulin sensitivity (SI) and secretion by liquid meal tolerance test, and body composition by dual energy X-ray absorptiometry. RESULTS: Despite similar average BMI percentiles among normal weight OGD versus CTRL, and overweight OGD vs. CTRL, OGD had greater total %fat and trunk fat adjusted for leg fat compared with CTRL (P < 0.05). Overweight children had lower SI (P < 0.05) and greater basal, static, and total insulin secretion independent of SI (P < 0.05). OGD was independently associated with greater static insulin secretion (P < 0.05) and the interaction between OGD and overweight was associated with greater basal insulin secretion independent of SI (P < 0.01). OGD and overweight were each associated with lower high-density lipoprotein-cholesterol (HDL-C) (P < 0.05). CONCLUSION: Intrauterine exposure to gestational diabetes was associated with greater central adiposity and insulin secretion, and lower HDL-C, irrespective of current weight status. Future research should examine respective contributions of the intrauterine environment and of underlying genotype on children's metabolic health. PMID- 22308219 TI - The value of multislice spiral CT features of cavitary walls in differentiating between peripheral lung cancer cavities and single pulmonary tuberculous thick walled cavities. AB - OBJECTIVES: Form discordance of cavity walls (FDCW) and form concordance of cavity walls (FCCW) in multislice spiral CT (MSCT) were investigated to determine their value in differentiating between peripheral lung cancer cavities and single pulmonary tuberculous thick-walled cavities. An assessment of the role of multiplanar reconstruction (MPR) in detecting FDCW and FCCW was also performed. METHODS: MSCT cross-sectional images of 116 consecutive cases (including 60 cases with available MPR images) with peripheral lung cancer cavities and 118 consecutive cases (including 62 cases with available MPR images) with single pulmonary tuberculous thick-walled cavities (wall thickness >3 mm) were retrospectively analysed. According to the characteristics of cavitary internal and external walls on MSCT, these cavities were divided into two types (FDCW and FCCW). FDCW was further divided into three subtypes (FDCW-I, FDCW-II and FDCW III); FCCW was further divided into two subtypes (FCCW-I and FCCW-II). RESULTS: On the cross-sectional and MPR images, the total detection rate of FDCW-I and FDCW-III in peripheral lung cancer cavities was 76.7% (89/116) and 93.3% (56/60), respectively, whereas the total detection rate of FCCW-I and FCCW-II in single pulmonary tuberculous thick-walled cavities was 75.4% (89/118) and 91.9% (57/62), respectively. CONCLUSIONS: FDCW-I, FDCW-III, FCCW-I and FCCW-II were valuable in differentiating between peripheral lung cancer cavities and single pulmonary tuberculous thick-walled cavities. MPR could improve the detection of FDCW-I and FDCW-III in peripheral lung cancer cavities and FCCW-I and FCCW-II in single pulmonary tuberculous thick-walled cavities. PMID- 22308220 TI - Estimation of paediatric organ and effective doses from dental cone beam CT using anthropomorphic phantoms. AB - OBJECTIVES: Cone beam CT (CBCT) is an emerging X-ray technology applied in dentomaxillofacial imaging. Previous published studies have estimated the effective dose and radiation risks using adult anthropomorphic phantoms for a wide range of CBCT units and imaging protocols. METHODS: Measurements were made five dental CBCT units for a range of imaging protocols, using 10-year-old and adolescent phantoms and thermoluminescent dosimeters. The purpose of the study was to estimate paediatric organ and effective doses from dental CBCT. RESULTS: The average effective doses to the 10-year-old and adolescent phantoms were 116 MUSv and 79 MUSv, respectively, which are similar to adult doses. The salivary glands received the highest organ dose and there was a fourfold increase in the thyroid dose of the 10-year-old relative to that of the adolescent because of its smaller size. The remainder tissues and salivary and thyroid glands contributed most significantly to the effective dose for a 10-year-old, whereas for an adolescent the remainder tissues and the salivary glands contributed the most significantly. It was found that the percentage attributable lifetime mortality risks were 0.002% and 0.001% for a 10-year-old and an adolescent patient, respectively, which are considerably higher than the risk to an adult having received the same doses. CONCLUSION: It is therefore imperative that dental CBCT examinations on children should be fully justified over conventional X-ray imaging and that dose optimisation by field of view collimation is particularly important in young children. PMID- 22308221 TI - A child with skin nodules and extensive soft tissue calcification. PMID- 22308222 TI - Early-stage malignant peripheral nerve sheath tumour arising from a solitary neurofibroma. AB - We report a case of early-stage malignant peripheral nerve sheath tumour (MPNST) found in a solitary neurofibroma, and its CT and MRI findings. A 19-year-old male with no known history of a neurofibromatosis presented with a painless swelling in the left forearm. CT and MRI scans showed a well-circumscribed, intermuscular mass, which was 6.0 cm in diameter and contained a strongly enhanced 1.0 cm nodular structure with surrounding oedema. Peripheral nerve continuity with the mass was not seen. Histological evaluation proved the nodular structure was an MPNST component completely surrounded by neurofibroma. Following an excisional biopsy with wide margins, the patient was followed up for a year without treatment and no recurrence was observed. PMID- 22308223 TI - Gastric haemolymphangioma: a literature review and report of one case. AB - Gastric haemolymphangioma is a very rare benign tumour. Pathologically, it is composed of lymphatic vessels and blood vessels. Only a few cases of haemolymphangioma have been reported in the literature so far, all of which developed at sites other than the stomach. The authors believe that a haemolymphangioma occurring in the stomach has not been previously reported. The patient was a healthy 68-year-old male who had felt light epigastric discomfort for 3 months. A CT scan and a gastrofiberscope examination revealed a well demarcated mass on the posterior wall of the stomach near the lesser curvature. The mass was successfully removed by surgery. During the 18-month follow-up period, the patient was asymptomatic with no recurrence. In this case report, we discuss the imaging findings as well as the pathological features of this unusual case, with a review of the related literature. PMID- 22308224 TI - Diagnosis of a biliary cystadenoma demonstrating communication with the biliary system by MRI using a hepatocyte-specific contrast agent. AB - Biliary cystadenomas are predominately benign tumours that have a low malignant potential. We present a case of a 30-year-old female with a histopathological confirmation of a biliary cystadenoma following resection. The diagnosis was made pre-operatively by MRI using the hepatocyte-specific contrast agent gadobenate dimeglumine (Gd-BOPTA) (MultiHance; Bracco Diagnostics Inc., Princeton, NJ). At the biliary excretory phase, delayed phase images demonstrated communication between the multilocular cystic mass and the biliary tree, which helped to confirm the diagnosis of biliary cystadenoma. This highlights the beneficial use of hepatocyte-specific agents for their dual function as an extracellular agent and a hepatobiliary agent. PMID- 22308225 TI - Desmoid tumour (aggressive fibromatosis) of the colon mimics malignancy on dual time-point 18F-FDG PET/CT imaging. AB - A 58-year-old female who presented with a lower gastrointestinal bleed was referred for an (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT after a colonoscopy revealed a submucosal mass in the ascending colon. The PET/CT confirmed the presence of an FDG-avid mass in the ascending colon with no other FDG-avid abnormalities. Dual time-point imaging was performed and showed a significant increase in FDG uptake in the mass, which raised strong suspicion of a colon malignancy. Although an initial biopsy of the mass did not show evidence of neoplasia, a decision was made to proceed with a right hemicolectomy based on high clinical and imaging suspicion of malignancy. Histological evaluation of the hemicolectomy revealed a benign colon desmoid tumour. PMID- 22308226 TI - Intracranial extracerebral neuroglial heterotopia with parapharyngeal extension: pre-natal and post-natal imaging findings. AB - We report an unusual case of intracranial extracerebral neuroglial heterotopia (IENH) presenting with parapharyngeal extension. Neuroglial heterotopias are rarely reported pre-natally and, to our knowledge, there are no reported cases presenting pre-natal imaging findings of IENH with parapharyngeal extension. Because pre- and post-natal imaging studies are essential to diagnose IENH and plan surgical treatment, radiologists should be familiar with this rare condition. PMID- 22308227 TI - Bilateral persistent hypoglossal arteries: MRI findings. AB - Persistence of foetal anastomoses between carotid and vertebrobasilar arteries is well recognised, but their bilateral presence is rare. We report a case of bilateral persistent hypoglossal arteries. Absence of bilateral vertebral arteries was incidentally noted on neck ultrasound examination. Subsequent MRI confirmed this and revealed persistent hypoglossal arteries that arose bilaterally from the cervical internal carotid artery, entered the cranium through the hypoglossal canal and joined the lower portion of the basilar artery. PMID- 22308229 TI - Elevated angiotensin II in rat nodose ganglia primes diabetes-blunted arterial baroreflex sensitivity: involvement of NADPH oxidase-derived superoxide. AB - Clinical trials and experimental animal studies have confirmed the contribution of arterial baroreflex impairment in causing excess morbidity and mortality in type-1 diabetes. Our previous study has shown that angiotensin II (Ang II)-NADPH oxidase-superoxide signaling is associated with the reduced cell excitability in the aortic baroreceptor neurons (a primary afferent limb of the arterial baroreflex) from diabetic rats. In this study, we examined whether above mentioned signaling might contribute to the blunted baroreflex sensitivity in streptozotocin-induced diabetic rats. Using Ang II (125)I radioimmunoassay and lucigenin chemiluminescence method, we found Ang II concentration, NADPH oxidase activity, and superoxide production in the nodose ganglia were enhanced in diabetic rats, compared to sham rats. As an index of the arterial baroreflex sensitivity, the reflex decreases in blood pressure and heart rate evoked by unilateral steady-frequency aortic depressor nerve stimulation were attenuated in diabetic rats. Local microinjection (50 nl) of losartan (an AT(1) receptor antagonist, 1 nmol), apocynin (a NADPH oxidase inhibitor, 1 nmol), and tempol (a superoxide dismutase mimetic, 10 nmol) into the nodose ganglia significantly improved the arterial baroreflex sensitivity in diabetic rats. In addition, these three chemicals also normalized exogenous Ang II-attenuated arterial baroreflex sensitivity in sham rats. These results indicate that overactivation of the Ang II-NADPH oxidase-superoxide signal pathway in the nodose ganglia contributes to the blunted baroreflex sensitivity in diabetes. PMID- 22308228 TI - Role of CD8 T Cell Replicative Senescence in Human Aging and in HIV-mediated Immunosenescence. AB - As humans age, their immune systems undergo a process known as immunosenescence. This global aging of the immune system is associated with increased susceptibility to infectious diseases and cancer, reduced effectiveness of vaccination, increased autoimmune phenomena, and tissue damage due to dysregulated inflammation. One hallmark feature of immunosenescence is the accumulation of late-differentiated memory CD8 T cells with features of replicative senescence, such as inability to proliferate, absence of CD28 expression, shortened telomeres, loss of telomerase activity, and enhanced secretion of inflammatory cytokines. The proportion of senescent CD8 T cells increases progressively with age, and often consists of oligoclonal populations that are specific for cytomegalovirus (CMV) antigens. In addition, there is evidence that senescent memory CD8 T cells acquire suppressive functions and may also contribute to carcinogenesis. Chronic HIV disease, even when controlled through antiretroviral therapy (ART), is associated with accelerated immunosenescence, as evidenced by the higher numbers of senescent memory CD8 T cells and increased inflammatory milieu. Interestingly, even in HIV disease, a high proportion of late-differentiated, putatively senescent, memory CD8 T cells are specific for CMV antigens. As in age-related immunosenescence, these HIV associated changes result in dysregulated immunity, chronic diseases linked to inflammatory damage, and increased morbidity and mortality. This review explores the evidence for CD8 T cell replicative senescence in vitro and in vivo, in the context of both chronological aging and HIV-mediated immunosenescence. We also highlight an important gap in our understanding of human immunosenescence, since all the studies to date have focused on peripheral blood, which contains a minority of the total body lymphocyte population. PMID- 22308230 TI - Reactivity and its association with body mass index across days on food checklists. AB - Characterizing relationships between diet, body weight, and health is complicated by reporting errors in dietary intake data that are associated with body weight. The objectives of this study were to assess changes in reporting across days (reactivity) on food checklists and associations between reactivity and body mass index (BMI) using data from two cross-sectional studies: 1) the Recontacting Participants in the Observing Protein and Energy Nutrition study (n = 297), which was conducted in 2003-2004 and included a 7-day checklist and a 4-day food record (FR), and 2) the America's Menu Daily Food Report Study (n=530), which was conducted in 1996 and included a 30-day checklist. Zero-inflated Poisson regression was used to assess effects of reporting day on frequency of consumption for the checklists and number of items reported for the FR. Interactions between day and BMI were tested using contrast statements. Frequency of reported consumption declined across days among males and females for total items and many of the eight food groups on the 7-day checklist; among females, the effect of reporting day differed by BMI category for the meat, fish, and poultry group. Smaller declines across days were observed for some of the 22 food groups on the 30-day checklist; no interactions with BMI were apparent. No reporting day effects were observed in the FR data. The results suggest inconsistent reactivity across days, possibly reflecting changes in reporting or consumption behavior. However, the effects are generally small and independent of body weight, suggesting that checklists are potentially useful for the study of body weight and diet. PMID- 22308231 TI - Congenital dislocation of the knee. PMID- 22308232 TI - Nonsuppurative encephalitis in a dog. AB - A 4-year-old male German Hunting Terrier presented with tremor, dyspnea, trismus, spasms of the musculature of the larynx and pharynx, and hypothermia and subsequently died despite intensive clinical care. Prior clinical signs included vomitus and diarrhea. Microscopic examination of the brain revealed a multifocal nonsuppurative brain stem encephalitis; a few intralesional neurons contained intranuclear inclusions. By immunohistochemistry, Aujeszky disease virus (Suid herpesvirus 1) antigen was detected in neurons in the brain and in ganglion cells of the trigeminal ganglia. Viral culture of brain tissue confirmed the presence of Aujeszky disease virus. Histopathologic findings in the brain with the identification of Aujeszky disease virus by immunohistochemistry and polymerase chain reaction are consistent with Aujeszky disease virus-induced encephalitis. Sequencing revealed a 100% homology of the isolated Aujeszky disease virus with Aujeszky disease virus isolates of wild boar from Eastern Germany. PMID- 22308233 TI - Cutaneous lymphomas in European pet rabbits (Oryctolagus cuniculus). AB - Cutaneous lymphoma is a common skin neoplasm of pet rabbits in Europe but is rarely reported in pet rabbits in North America. These neoplasms have not been previously characterized, nor has the cause for the apparent predilection for cutaneous lymphoma in European pet rabbits compared with North American pet rabbits been investigated. In this retrospective study, the authors morphologically and immunohistochemically characterized 25 cutaneous lymphomas in European pet rabbits according to the World Health Organization classification. Tumors were classified as diffuse large B cell lymphomas, with 14 lymphomas exhibiting a centroblastic/centrocytic subtype and 11 tumors exhibiting a T cell rich B cell subtype. To investigate a potential viral etiology of these lymphomas, 3 diffuse large B cell and 3 T cell-rich B cell lymphomas were evaluated by polymerase chain reaction for retroviral and herpesviral genes. Neither virus was detected. In contrast to other domestic animals, cutaneous lymphomas in European pet rabbits were highly pleomorphic and frequently contained multinucleated giant cells. Unexpectedly, the second most common subtype was T cell-rich B cell lymphoma, a subtype that is rare in species other than horses. Based on a limited number of samples, there was no support for a viral etiology that would explain the higher incidence of lymphoma in European pet rabbits compared with American pet rabbits. Further investigation into genetic and extrinsic factors associated with the development of these tumors is warranted. PMID- 22308234 TI - Pneumocystis carinii causes a distinctive interstitial pneumonia in immunocompetent laboratory rats that had been attributed to "rat respiratory virus". AB - A prevalent and distinctive infectious interstitial pneumonia (IIP) of immunocompetent laboratory rats was suspected to be caused by a putative virus, termed rat respiratory virus, but this was never substantiated. To study this disease, 2 isolators were independently populated with rats from colonies with endemic disease, which was perpetuated by the regular addition of naive rats. After Pneumocystis was demonstrated by histopathology and polymerase chain reaction (PCR) in the lungs of rats from both isolators and an earlier bedding transmission study, the relationship between Pneumocystis and IIP was explored further by analyzing specimens from 3 contact transmission experiments, diagnostic submissions, and barrier room breeding colonies, including 1 with and 49 without IIP. Quantitative (q) PCR and immunofluorescence assay only detected Pneumocystis infection and serum antibodies in rats from experiments or colonies in which IIP was diagnosed by histopathology. In immunocompetent hosts, the Pneumocystis concentration in lungs corresponded to the severity and prevalence of IIP; seroconversion occurred when IIP developed and was followed by the concurrent clearance of Pneumocystis from lungs and resolution of disease. Experimentally infected immunodeficient RNU rats, by contrast, did not seroconvert to Pneumocystis or recover from infection. qPCR found Pneumocystis at significantly higher concentrations and much more often in lungs than in bronchial and nasal washes and failed to detect Pneumocystis in oral swabs. The sequences of a mitochondrial ribosomal large-subunit gene region for Pneumocystis from 11 distinct IIP sources were all identical to that of P. carinii. These data provide substantial evidence that P. carinii causes IIP in immunocompetent rats. PMID- 22308235 TI - On the environmental stress that reshapes our vessels. PMID- 22308236 TI - Proarrhythmia in KCNJ2-linked short QT syndrome: insights from modelling. AB - AIMS: One form of the short QT syndrome (SQT3) has been linked to the D172N gain in-function mutation to Kir2.1, which preferentially increases outward current through channels responsible for inward rectifier K(+) current (I(K1)). This study investigated mechanisms by which the Kir2.1 D172N mutation facilitates and perpetuates ventricular arrhythmias. METHODS AND RESULTS: The ten Tusscher et al. model for human ventricular action potentials (APs) was modified to incorporate changes to I(K1) based on experimentally observed changes to Kir2.1 function: both heterozygous (WT-D172N) and homozygous (D172N) mutant scenarios were studied. Cell models were incorporated into heterogeneous one-dimensional (1D), 2D tissue, and 3D models to compute the restitution curves of AP duration (APD R), effective refractory period (ERP-R), and conduction velocity (CV). Temporal and spatial vulnerability of ventricular tissue to re-entry was measured and dynamic behaviour of re-entrant excitation waves (lifespan and dominant frequency) in 2D and 3D models of the human ventricle was characterized. D172N 'mutant' I(K1) led to abbreviated APD and ERP, as well as steeper APD-R and ERP-R curves. It reduced tissue excitability at low excitation rates but increased it at high rates. It increased tissue temporal vulnerability for initiating re entry, but reduced the minimal substrate size necessary to sustain re-entry. SQT3 'mutant' I(K1) also stabilized and accelerated re-entrant excitation waves, leading to sustained rapid re-entry. CONCLUSION: Increased I(K1) due to the Kir2.1 D172N mutation increases arrhythmia risk due to increased tissue vulnerability, shortened ERP, and altered excitability, which in combination facilitate initiation and maintenance of re-entrant circuits. PMID- 22308237 TI - Thrombospondin-2 prevents cardiac injury and dysfunction in viral myocarditis through the activation of regulatory T-cells. AB - AIMS: Thrombospondin-2 (TSP-2) modulates matrix integrity and myocyte survival in the hypertensive or ageing heart. Whether TSP-2 may affect cardiac inflammation and injury, in particular during acute viral myocarditis, is completely unknown. METHODS AND RESULTS: Therefore, mortality, cardiac inflammation, and function were assessed in TSP-2-null (KO) and wild-type (WT) mice in human Coxsackie virus B3 (CVB3)-induced myocarditis. TSP-2 KO had an increased mortality when compared with WT mice during viral myocarditis. The absence of TSP-2 resulted in increased cardiac inflammation and injury at 14 days, which resulted in depressed systolic function [fractional shortening (FS); 34 +/- 2.6 in WT vs. 24 +/- 1.8 in KO mice, P< 0.05] and increased cardiac dilatation (end-diastolic dimensions, mm; 3.7 +/- 0.09 in WT vs. 4.8 +/- 0.06 in KO mice, P< 0.05) 35 days post-infection. Lack of TSP-2 resulted in a decreased activation of the anti-inflammatory T-regulatory cells, as indicated by a lower number of CD25-positive T-cells, and significantly decreased gene expression of regulatory T-cell markers, Foxp3 and CTLA-4. Finally, overexpression of TSP-2 in WT hearts using cardiotropic vectors derived from adeno-associated virus serotype 9 (AAV9) inhibited cardiac inflammation and injury at 14 days and improved cardiac function at 35 days post-CVB3 infection when compared with control AAV9. CONCLUSION: TSP-2 has a protective role against cardiac inflammation, injury, and dysfunction in acute viral myocarditis. PMID- 22308238 TI - Whole-genome analysis of gene expression associates the ubiquitin-proteasome system with the cardiomyopathy phenotype in disease-sensitized congenic mouse strains. AB - AIMS: Penetrance and phenotypic expressivity of cardiomyopathies are modulated by modifier genes both in model systems and patients. We aimed to dissect the disease-modifying mechanisms by examining genome-wide gene expression in a new set of mouse (Mus musculus) congenic strains. METHODS AND RESULTS: Mutant alleles of the genes calsarcin-1 (Myoz2), sarcoglycan-delta (Sgcd), and muscle LIM protein (Csrp2) were each transferred onto inbred strain backgrounds C57BL/6, C3H/He, 129S1/Sv, and FVB/N, respectively. At 9-10 weeks of age, left ventricular pump function (fractional shortening, FS) was determined by echocardiography in non-sedated congenic animals. Gene expression was then analysed in myocardial tissue using the Affymetrix Mouse 430.2 microarray platform. Variance stabilization, linear mixed-effects modelling, correlations, gene functional classification, and pathway analysis were conducted using the standard software. Strain background FVB/N appeared to protect against the consequences of gene inactivation. Sgcd-deficient congenics showed normal FS, which was consistent with their hypertrophic cardiomyopathy phenotype. Animals with other allele/background combinations developed an impaired ventricular pump function (FS <65%). Gender did not influence FS significantly, yet it determined the sets of genes that were differentially expressed in mice with low FS. In particular, genes encoding the elements of the ubiquitin-proteasome system (UPS) were strongly correlated with the cardiac impairment (absolute Spearman r >= 0.7) in both males and females. CONCLUSION: Gene expression profiling in a novel set of congenic strains revealed an association between the UPS and myocardial contractile function, indicating that the UPS may be an important modifier of phenotypic variability in cardiomyopathies. PMID- 22308239 TI - Standardizing the structure of stroke clinical and epidemiologic research data: the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Common Data Element (CDE) project. AB - BACKGROUND AND PURPOSE: The National Institute of Neurological Disorders and Stroke initiated development of stroke-specific Common Data Elements (CDEs) as part of a project to develop data standards for funded clinical research in all fields of neuroscience. Standardizing data elements in translational, clinical, and population research in cerebrovascular disease could decrease study start-up time, facilitate data sharing, and promote well-informed clinical practice guidelines. METHODS: A working group of diverse experts in cerebrovascular clinical trials, epidemiology, and biostatistics met regularly to develop a set of stroke CDEs, selecting among, refining, and adding to existing, field-tested data elements from national registries and funded trials and studies. Candidate elements were revised on the basis of comments from leading national and international neurovascular research organizations and the public. RESULTS: The first iteration of the National Institute of Neurological Disorders and Stroke (NINDS) stroke-specific CDEs comprises 980 data elements spanning 9 content areas: (1) biospecimens and biomarkers; (2) hospital course and acute therapies; (3) imaging; (4) laboratory tests and vital signs; (5) long-term therapies; (6) medical history and prior health status; (7) outcomes and end points; (8) stroke presentation; and (9) stroke types and subtypes. A CDE website provides uniform names and structures for each element, a data dictionary, and template case report forms, using the CDEs. CONCLUSIONS: Stroke-specific CDEs are now available as standardized, scientifically vetted, variable structures to facilitate data collection and data sharing in cerebrovascular patient-oriented research. The CDEs are an evolving resource that will be iteratively improved based on investigator use, new technologies, and emerging concepts and research findings. PMID- 22308240 TI - A structured reading algorithm improves telemetric detection of atrial fibrillation after acute ischemic stroke. AB - BACKGROUND AND PURPOSE: Anticoagulation is a highly effective secondary prevention in patients with cardioembolic stroke and atrial fibrillation/flutter (AF). However, the condition remains underdiagnosed, because paroxysmal AF may be missed by diagnostic tests in the acute phase. In this study, the sensitivity of AF detection was assessed for serial electrocardiographic recordings and continuous stroke unit telemetric monitoring with or without a structured algorithm to analyze telemetric data (SEA-AF). METHODS: Three hundred forty-six consecutive patients with acute ischemic stroke were prospectively included and subjected to standard telemetric monitoring. In addition, telemetric data were separately analyzed following SEA-AF, consisting of a structured evaluation of episodes with high risk for AF and a chronological beat-to-beat screening of the full registration. Serial electrocardiograms were conducted in 24-hour intervals. RESULTS: Median effective telemetry monitoring time was 75.5 hours (interquartile range 64-86 hours). Overall, AF was diagnosed in 119 of 346 patients (34.4%). The structured reading algorithm was the most sensitive method to detected AF. Conventional telemetry and serial electrocardiographic assessments were less effective. However, only 35% of patients with previously documented paroxysmal AF and negative baseline electrocardiogram demonstrated AF episodes during monitoring. CONCLUSIONS: Continuous stroke unit telemetry using SEA-AF shows a significantly higher detection rate for AF compared with daily electrocardiographic assessments and standard telemetry without structured reading. The low overall probability to detect paroxysmal AF with either method during the first days after stroke demonstrates the urgent need for complementary diagnostic strategies such as long-term monitoring and frequent follow-up assessments. Clinical Trial Registration- URL: www.clinicaltrials.gov. Unique identifier: NCT01177748. PMID- 22308241 TI - Cognitive and graded activity training can alleviate persistent fatigue after stroke: a randomized, controlled trial. AB - BACKGROUND AND PURPOSE: Fatigue is a common, persistent consequence of stroke, and no evidence-based treatments are currently available to alleviate fatigue. A new treatment combining cognitive therapy (CO) with graded activity training (GRAT), called COGRAT, was developed to alleviate fatigue and fatigue-related symptoms. This study compared the effectiveness of the COGRAT intervention with a CO-only intervention after a 3-month qualification period without intervention. METHODS: This randomized, controlled, assessor-blind clinical trial was conducted in 8 rehabilitation centers. Eighty-three stroke patients (>4 months after stroke) were randomly assigned to 12 weeks of CO or COGRAT after qualification. Seventy-three patients completed treatment and 68 were available at follow-up. Primary outcomes (Checklist Individual Strength-subscale Fatigue (CIS-f); self observation list-fatigue (SOL-f)) and secondary outcomes (Hospital Anxiety and Depression Scale, Stroke-Adapted Sickness Impact Profile, SOL-pain, SOL-sleep-D, 6-minute walk test) were collected at baseline (before and after qualification period) and after treatment (immediate and 6-month follow-up). RESULTS: The qualification period showed stable outcome measures. Both treatments showed significant beneficial effects on fatigue (CIS-f: eta(p)(2)=0.48, P<0.001) and other outcomes (except pain and anxiety) with intention-to-treat analyses. Gains for the COGRAT group exceeded those in the CO group on number of individuals showing clinical improvement on the CIS-f (>=8 points: 58% versus 24%) and on physical endurance (eta(p)(2)=0.20, P<0.001). CONCLUSIONS: A 12-week cognitive therapy program can alleviate persistent fatigue after stroke. The best results are obtained when cognitive therapy is augmented with graded activity training. Clinical Trial Registration- URL: http://www.trialregister.nl. Unique identifier: NTR2704. PMID- 22308242 TI - Carotid revascularization strategies: the need for more data. PMID- 22308243 TI - Critique of apixaban versus warfarin in patients with atrial fibrillation. PMID- 22308244 TI - Role of central nervous system periostin in cerebral ischemia. AB - BACKGROUND AND PURPOSE: Although periostin, an extracellular matrix glycoprotein, plays pivotal roles in survival, migration, and regeneration in various cells, its expression and function in the brain are still unknown. Here, we investigated the expression and role of periostin in the ischemic brain. METHODS: Expression of full-length periostin (periostin 1 [Pn1]) and its splicing variant lacking exon 17 (periostin 2 [Pn2]) was examined by real-time reverse transcription polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical staining in male C57BL6/J mice. The actions of periostin were examined in adult primary neuronal culture and in a transient middle cerebral artery occlusion (tMCAo) model. RESULTS: Expression of Pn2, but not of Pn1, mRNA was markedly changed after tMCAo. Pn2 mRNA was decreased in the ischemic core at 3 hours after ischemia. At 24 hours, Pn2 mRNA was significantly increased in both the peri ischemic and ischemic regions. Periostin was mainly observed in neurons in normal brain. However, neuronal expression of periostin was decreased temporarily in the ischemic region, but increased in astrocytes and around endothelial cells at 24 hours after tMCAo. Of importance, intracerebroventricular injection of Pn2 resulted in a significant reduction in infarct volume at 24 hours after tMCAo associated with phosphorylation of Akt. Also, the Pn2-treated mice survived longer until 1 week after tMCAo. Pn2 significantly inhibited neuronal death under hypoxia and stimulated neurite outgrowth. CONCLUSIONS: Here, we demonstrated that periostin was expressed in the brain, and exogenous Pn2 exhibited neuroprotective effects and accelerated neurite outgrowth. Additional studies on periostin may provide new insights into the treatment of ischemic stroke. PMID- 22308245 TI - Poststroke fatigue: a hint, but no definite word on therapy yet. PMID- 22308246 TI - The types of neurological deficits might not justify withholding treatment in patients with low total National Institutes of Health Stroke Scale scores. AB - BACKGROUND AND PURPOSE: There is controversy regarding the threshold for treating patients with mild strokes. Physicians often withhold acute treatment in these patients if they perceive the symptoms are not going to be disabling. We tested the appropriateness of this practice by analyzing the relationship between specific neurological deficits in the National Institutes of Health Stroke Scale (NIHSS) score and long-term outcome among patients with a low total NIHSS score. METHODS: We performed a secondary analysis on those patients enrolled in the Trial of ORG 10172 in Acute Stroke Treatment that presented within 4.5 hours of symptom onset and had a baseline NIHSS score <=6 (n=194). We performed multivariate logistic regression analyses using very favorable outcome at 3 months as the outcome variable and each of the individual items of the baseline NIHSS examination and syndromic combinations of NIHSS scores as predictors. The analyses were adjusted for potential confounders with and without adjusting for total NIHSS score. RESULTS: Baseline total NIHSS scores were inversely associated with very favorable outcome at 3 months. No individual NIHSS item, or syndromic combination of NIHSS scores, was independently associated with very favorable outcome in a consistent manner after accounting for confounders and collinearity. CONCLUSIONS: The types of neurological deficits in the baseline NIHSS are not independent predictors of long-term prognosis for patients with mild stroke. These exploratory findings argue against the practice of withholding reperfusion treatment in patients with mild stroke when the types of baseline NIHSS deficits are perceived to be nondisabling. PMID- 22308247 TI - Ischemic transient neurological events identified by immune response to cerebral ischemia. AB - BACKGROUND AND PURPOSE: Deciphering whether a transient neurological event (TNE) is of ischemic or nonischemic etiology can be challenging. Ischemia of cerebral tissue elicits an immune response in stroke and transient ischemic attack (TIA). This response, as detected by RNA expressed in immune cells, could potentially distinguish ischemic from nonischemic TNE. METHODS: Analysis of 208 TIAs, ischemic strokes, controls, and TNE was performed. RNA from blood was processed on microarrays. TIAs (n=26) and ischemic strokes (n=94) were compared with controls (n=44) to identify differentially expressed genes (false discovery rate <0.05, fold change >=1.2). Genes common to TIA and stroke were used predict ischemia in TIA diffusion-weighted imaging-positive/minor stroke (n=17), nonischemic TNE (n=13), and TNE of unclear etiology (n=14). RESULTS: Seventy-four genes expressed in TIA were common to those in ischemic stroke. Functional pathways common to TIA and stroke related to activation of innate and adaptive immune systems, involving granulocytes and B cells. A prediction model using 26 of the 74 ischemia genes distinguished TIA and stroke subjects from control subjects with 89% sensitivity and specificity. In the validation cohort, 17 of 17 TIA diffusion-weighted imaging-positive/minor strokes were predicted to be ischemic, and 10 of 13 nonischemic TNE were predicted to be nonischemic. In TNE of unclear etiology, 71% were predicted to be ischemic. These subjects had higher ABCD(2) scores. CONCLUSIONS: A common molecular response to ischemia in TIA and stroke was identified, relating to activation of innate and adaptive immune systems. TNE of ischemic etiology was identified based on gene profiles that may be of clinical use once validated. PMID- 22308248 TI - Avoiding thrombolysis in patients with mild stroke: is it SMART? PMID- 22308249 TI - Letter by Charidimou et al regarding article, "Blood pressure reduction, decreased diffusion on MRI, and outcomes after intracerebral hemorrhage". PMID- 22308250 TI - Valid items for screening dysphagia risk in patients with stroke: a systematic review. AB - BACKGROUND AND PURPOSE: Screening for dysphagia is essential to the implementation of preventive therapies for patients with stroke. A systematic review was undertaken to determine the evidence-based validity of dysphagia screening items using instrumental evaluation as the reference standard. METHODS: Four databases from 1985 through March 2011 were searched using the terms cerebrovascular disease, stroke deglutition disorders, and dysphagia. Eligibility criteria were: homogeneous stroke population, comparison to instrumental examination, clinical examination without equipment, outcome measures of dysphagia or aspiration, and validity of screening items reported or able to be calculated. Articles meeting inclusion criteria were evaluated for methodological rigor. Sensitivity, specificity, and predictive capabilities were calculated for each item. RESULTS: Total source documents numbered 832; 86 were reviewed in full and 16 met inclusion criteria. Study quality was variable. Testing swallowing, generally with water, was the most commonly administered item across studies. Both swallowing and nonswallowing items were identified as predictive of aspiration. Neither swallowing protocols nor validity were consistent across studies. CONCLUSIONS: Numerous behaviors were found to be associated with aspiration. The best combination of nonswallowing and swallowing items as well as the best swallowing protocol remains unclear. Findings of this review will assist in development of valid clinical screening instruments. PMID- 22308251 TI - Lipid and lipoprotein biomarkers and the risk of ischemic stroke in postmenopausal women. AB - BACKGROUND: Few studies simultaneously investigated lipids and lipoprotein biomarkers as predictors of ischemic stroke. The value of these biomarkers as independent predictors of ischemic stroke remains controversial. METHODS: We conducted a prospective nested case-control study among postmenopausal women from the Women's Health Initiative Observational Study to assess the relationship between fasting lipids (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides), lipoproteins (LDL, HDL, and very low-density lipoprotein [VLDL] particle number and size, intermediate-density lipoprotein [IDL] particle number, and lipoprotein (a)), and risk of ischemic stroke. Among women free of stroke at baseline, 774 ischemic stroke patients were matched according to age and race to control subjects, using a 1:1 ratio. RESULTS: In bivariate analysis, baseline triglycerides (P<0.001), IDL particles (P<0.01), LDL particles (P<0.01), VLDL triglyceride (P<0.001), VLDL particles (P<0.01), VLDL size (P<0.001), LDL size (P=0.03), and total/HDL cholesterol ratio (P<0.01) were significantly higher among women with incident ischemic stroke, whereas levels of HDL-C (P<0.01) and HDL size (P<0.01) were lower. No significant baseline difference for total cholesterol (P=0.15), LDL-C (P=0.47), and lipoprotein (a) (P=0.11) was observed. In multivariable analysis, triglycerides (odds ratio for the highest versus lowest quartile, 1.56; 95% confidence interval, 1.13-2.17; P for trend=0.02), VLDL size (odds ratio, 1.59; 95% confidence interval, 1.10-2.28; P for trend=0.03), and IDL particle number (odds ratio, 1.46; 95% confidence interval, 1.04-2.04; P for trend=0.02) were significantly associated with ischemic stroke. CONCLUSIONS: Among a panel of lipid and lipoprotein biomarkers, baseline triglycerides, VLDL size, and IDL particle number were significantly associated with incident ischemic stroke in postmenopausal women. PMID- 22308252 TI - The iScore predicts effectiveness of thrombolytic therapy for acute ischemic stroke. AB - BACKGROUND AND PURPOSE: Tools to predict the clinical response after intravenous thrombolytic therapy (tPA) are scarce. The iScore is an existing validated tool to estimate outcomes after an acute ischemic stroke. The purpose of this study was to determine the ability of the iScore to predict clinical response and risk of hemorrhagic transformation after tPA. METHODS: We applied the iScore (www.sorcan.ca/iscore) to patients presenting with an acute ischemic stroke at 11 stroke centers in Ontario, Canada, between 2003 and 2009 identified from the Registry of the Canadian Stroke Network. A cohort of patients with stroke treated at 154 centers in Ontario was used for external validation. We compared outcomes between patients receiving and not receiving tPA after adjusting for differences in baseline characteristics using propensity-score matching. Patients were stratified into 3 a priori defined groups according to stroke severity using the iScore. RESULTS: Among 12 686 patients with an acute ischemic stroke, 1696 (13.4%) received intravenous thrombolysis. Higher iScores were associated with poor outcomes in both the tPA and non-tPA groups (P<0.001). Among those at low and medium risk based on their iScores, tPA use was associated with a benefit in the primary outcome (relative risk, 0.74 for those with low-risk iScores; 95% CI, 0.67-0.84; relative risk, 0.88 for those with medium risk iScores; 95% CI, 0.84 0.93). There was no difference in clinical outcomes between matched patients receiving and not receiving tPA in the highest iScore group (relative risk, 0.97; 95% CI, 0.94-1.01). Similar results were observed for disability at discharge and length of stay. The incident risk of neurological deterioration and hemorrhagic transformation (any or symptomatic) with tPA increased with the iScore risk. Results were similar in the validation cohort for risk of poor outcome with tPA by iScore level. CONCLUSIONS: The iScore may be used to predict clinical response and risk of hemorrhagic complications after tPA for an acute ischemic stroke. Patients with high iScores may not have a clinically meaningful benefit from intravenous tPA at the time of carrying a higher risk of hemorrhagic complications. PMID- 22308253 TI - Silent intralesional microhemorrhage as a risk factor for brain arteriovenous malformation rupture. AB - BACKGROUND AND PURPOSE: We investigated whether brain arteriovenous malformation silent intralesional microhemorrhage, that is, asymptomatic bleeding in the nidal compartment, might serve as a marker for increased risk of symptomatic intracranial hemorrhage (ICH). We evaluated 2 markers to assess the occurrence of silent intralesional microhemorrhage: neuroradiological assessment of evidence of old hemorrhage-imaging evidence of bleeding before the outcome events-and hemosiderin positivity in hematoxylin and eosin-stained paraffin block sections. METHODS: We identified cases from our brain arteriovenous malformation database with recorded neuroradiological data or available surgical paraffin blocks. Using 2 end points, index ICH or new ICH after diagnosis (censored at treatment, loss to follow-up, or death), we performed logistic or Cox regression to assess evidence of old hemorrhage and hemosiderin positivity adjusting for age, sex, deep-only venous drainage, maximal brain arteriovenous malformation size, deep location, and associated arterial aneurysms. RESULTS: Evidence of old hemorrhage was present in 6.5% (n=975) of patients and highly predictive of index ICH (P<0.001; OR, 3.97; 95% CI, 2.1-7.5) adjusting for other risk factors. In a multivariable model (n=643), evidence of old hemorrhage was an independent predictor of new ICH (hazard ratio, 3.53; 95% CI, 1.35-9.23; P=0.010). Hemosiderin positivity was found in 36.2% (29.6% in unruptured; 47.8% in ruptured; P=0.04) and associated with index ICH in univariate (OR, 2.18; 95% CI, 1.03-4.61; P=0.042; n=127) and multivariable models (OR, 3.64; 95% CI, 1.11 12.00; P=0.034; n=79). CONCLUSIONS: The prevalence of silent intralesional microhemorrhage is high and there is evidence for an association with both index and subsequent ICH. Further development of means to detect silent intralesional microhemorrhage during brain arteriovenous malformation evaluation may present an opportunity to improve risk stratification, especially for unruptured brain arteriovenous malformations. PMID- 22308254 TI - Seven-day NIHSS is a sensitive outcome measure for exploratory clinical trials in acute stroke: evidence from the Virtual International Stroke Trials Archive. AB - BACKGROUND AND PURPOSE: Clinical trials in stroke typically measure outcome after 90 days. Earlier outcome assessment would reduce costs and may increase power. We aimed to compare the sensitivity of 4 end points (modified Rankin Scale [mRS] at 30 and 90 days, and National Institutes of Health Stroke Scale (NIHSS) at 7 and 90 days, analyzed as ordinal measures) to detect the established treatment effect of recombinant tissue-type plasminogen activator (rtPA). METHODS: Within the Virtual International Stroke Trials Archive, we compared rtPA-treated patients with untreated control subjects using a multiple resampling approach. From our total sample we drew 10 000 random samples of unique patients, constraining the sample sizes in treated and untreated groups to be equal. In each of these samples we tested for the treatment effect of rtPA by each of the 4 studied end points. The percentage of samples yielding significant results approximates the power of each end point at a given sample size. This process was repeated across a range of sample sizes, to determine the relationship between sample size and power for each of the 4 end points. RESULTS: For our 4 end points of mRS at 30 and 90 days, and NIHSS at 7 and 90 days the smallest sample sizes required to generate statistical power >80% were 620, 480, 370, and 420, respectively, making 7-day NIHSS the most sensitive end point. These results were supported by dichotomized analyses. CONCLUSIONS: Seven-day NIHSS score appears a sensitive end point that should be validated in randomized trial datasets for use in exploratory stroke trials. PMID- 22308255 TI - Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in patients with atrial fibrillation and prior stroke or transient ischemic attack. AB - BACKGROUND AND PURPOSE: The cost-effectiveness of dabigatran for stroke prevention in patients with atrial fibrillation and prior stroke or transient ischemic attack has not been directly assessed. METHODS: A Markov decision model was constructed using data from the Randomized Evaluation of Long-Term Therapy (RE-LY) trial, other trials of warfarin therapy for atrial fibrillation, and the published cost of dabigatran. We compared the cost and quality-adjusted life expectancy associated with 150 mg dabigatran twice daily versus warfarin therapy targeted to an international normalized ratio of 2 to 3. The target population was a cohort of patients aged >=70 years with nonvalvular atrial fibrillation, prior stroke or transient ischemic attack, and no contraindication to anticoagulation. RESULTS: In the base case, dabigatran was associated with 4.27 quality-adjusted life-years compared with 3.91 quality-adjusted life-years with warfarin. Dabigatran provided 0.36 additional quality-adjusted life-years at a cost of $9000, yielding an incremental cost-effectiveness ratio of $25,000. In sensitivity analyses, the cost-effectiveness of dabigatran was inversely related to the quality of international normalized ratio control achieved with warfarin therapy. In Monte Carlo analysis, dabigatran was cost-effective in 57% of simulations using a threshold of $50,000 per quality-adjusted life-year and 78% of simulations using a threshold of $100,000 per quality-adjusted life-year. CONCLUSIONS: Dabigatran appears to be cost-effective relative to warfarin for stroke prevention in patients with atrial fibrillation and prior stroke or transient ischemic attack. Our analysis is limited by its reliance on data from a substudy of a single randomized trial, and our results may not apply in settings with uncommonly good international normalized ratio control using warfarin. PMID- 22308256 TI - [Biological study in schizophrenia]. AB - Schizophrenia is associated with enormous morbidity, mortality, personal disability, and social cost. Although considerable research on schizophrenia has been performed, the etiology of this disease has not been fully elucidated. In recent years, imaging and genetic technologies have been developed dramatically. Disturbances in glutamate and GABAergic neurotransmission may underlie the pathophysiology of schizophrenia. We attempted an integrative review, of studies pertaining to recent advances of schizophrenia research with a focus on neuroimaging and genetic studies. Additionally, we present the preliminary findings of the clinical research in our outpatient unit, specialized for early intervention, at the University of Tokyo Hospital. PMID- 22308257 TI - [Recent progress in mood disorder research]. AB - When papers published in highly-prestigious journals in 2010 and 2011 were categorized, the number of papers on genestic studies was found to be the largest, followed by papers on brain imaging, postmortem brain studies, and animal model studies. Follow-up studies of the findings of initial genome-wide association analyses constitute a major part of genetic studies. Recent brain imaging studies were found to integrate previous findings that indicated altered responces of prefrontal cortex to cognitive stimuli and enhanced responces of amygdala to emotional faces. Reduced size of the hippocampus is reportedly not a result of stress but perhaps a vulnerability factor. Among animal model studies, molecular mechanisms underlying rapid anti-depressive effects of ketamine are drawing attention. The role of neurogenesis in fear memory and depression is complex, and a link between psychopathology and neuroscience may be needed to understand the roles of neurogenesis. Postmortem brain analyses are currently used to investigate several pathophysiological hypotheses related to the roles of monoamine, neuroplasticity, and neuroinflammation in depression, as well as the roles of GABAergic neurons and mitochondria in bipolar disorder. Several studies are integrating postmortem brain analysis and animal model studies. Genetic and neuroimaging studies of mood disorders have advanced, and neurobiological basis of the findings of these studies should be further elucidated in animal models and postmortem brains. PMID- 22308258 TI - [Anxiety disorder]. AB - We reviewed recent advances in biological studies of anxiety disorders. The most important achievement was the discovery of the neural circuits of fear in the 1990s by using an animal model in which conditioned fear was induced. In the 2000s, this discovery led to further elucidation of neurotransmitters involved in fear and the precise neuronal mechanism of fear conditioning, thereby improving the understanding of neuroimaging findings of patients with anxiety disorders. The amygdala is a central region that is associated with the generation of fear, and its inactivation diminishes fear. In humans, amygdala activation has been consistently reported in anxiety disorders, indicating that hyperactivation of the amygdala is involved in the pathogenesis of anxiety disorders. Serotonin plays a key role in the treatment of anxiety disorders, and selective serotonin reuptake inhibitors (SSRIs) are currently regarded the first-line drugs used as anxiolytics. From animal studies, the mechanism underlying the anxiolytic effect of SSRIs is hypothesized as follows: SSRIs inhibit the neuronal activities of the amygdala, and this inhibition decreases the level of fear and anxiety. Animal studies of fear conditioning have proposed new treatment strategies for anxiety disorders: D-cycloserine, propranolol, and reactivation-extinction procedure. Among them, D-cycloserine, which is used as an adjunct to psychotherapy to facilitate extinction of fear, has been investigated in several randomized controlled trials, and its efficacies for several anxiety disorders have been established. PMID- 22308259 TI - [Developmental disorders]. AB - Developmental disorders, which are usually diagnosed in infancy, childhood, or adolescence, include mental retardation, learning disorders, motor skills disorder, communication disorders, pervasive developmental disorders (PDD), attention-deficit hyperactivity disorder (ADHD), and tic disorders. Epidemiological studies have indicated that these disorders are characterized not only by high heritability (e.g., 0.80 for PDD) but also by their shared genetic etiology. Furthermore, retrospective or prospective longitudinal studies have revealed that adult psychiatric disorders are often preceded either by their juvenile counterparts (homotypic continuity) or by different disorders (heterotypic continuity). Recent genetic studies have detected copy number variants (CNVs; e.g., deletions on 1q21.1, 3q29, and 22q.11.21 and duplications on 16p11.2) as shared genetic factors for PDD, mental retardation, and schizophrenia. While these CNVs are generally very rare (<1%), their effect size is much larger than that of single nucleotide polymorphisms. Although the mechanism by which CNVs cause these abnormalities remains unclear, pleiotropic effect of CNVs may provide insights into the high rate of comorbidity among developmental disorders and heterotypic continuity between developmental disorders and adult disorders. In addition, longitudinal neuroimaging studies have provided evidence for irregularities in the typical trajectories in developmental disorders. For instance, retarded cortical development is identified in ADHD in cortical trajectory, and early acceleration of brain growth is identified in PDD. Finally, we outlined several research topics as the future direction for investigation of developmental disorders: a longitudinal clinical study in subjects with specific disorder-related CNVs; detailed analysis of genetic factors relevant to developmental disorders, including smaller CNVs and INDELs; and functional analysis of genetic factors by using induced pluripotent stem cell technology or non-human primate animal models. PMID- 22308260 TI - [Advances in biological psychiatry research on dementia: AD-FTLD spectrum]. AB - Neurodegenerative dementia, including Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD), is one of the main target areas for research in biological psychiatry. In this review, the historical view, present situation, and further development in dementia research have been discussed from the viewpoint of biological psychiatry. Considering the rapidly increasing number of dementia patients in Japan, the importance of dementia in clinical psychiatry service will keep increasing in the near future. Biological as well as psychosocial knowledge is required to elucidate the mechanism underlying dementia. Although the molecular mechanism underlying the pathological features of AD has not yet been fully elucidated, it can be placed under the concept of the AD-FTLD spectrum, in which loss of function of an important gene may result in accumulation of insoluble proteins inside and outside neurons. To develop disease-modifying drugs for AD and FTLD, elucidation of pathological events that occur earlier than abnormal protein deposition is essential. Early diagnosis and early intervention are important for overcoming these neurodegenerative dementia. PMID- 22308261 TI - [Alcohol and substance dependence]. AB - In this paper, we have outlined the neurobiological basis of alcohol and drug dependence. The prevalence of drug dependence is a serious social problem in many countries, including Japan. This problem involves many background factors, including those pertaining to medical sciences, socio economics, and politics. First, we briefly describe the findings pertaining to psychotomimetic drugs as a model of schizophrenia. The biological pathogenesis of schizophrenic disorders is still unknown. The symptoms of methamphetamine (MAP) and phencyclidine (PCP) psychoses are very similar to those of schizophrenic disorders involving hallucination or delusion. PCP causes not only positive symptoms but also negative symptoms. Therefore, it has been considered as a more comprehensive model of schizophrenia than other drugs. Furthermore, amotivational syndrome, which is observed in patients with chronic cannabis and organic solvent dependence, is similar to the negative symptoms of schizophrenia. Understanding the neurobiological basis of drug dependence by using the molecular biological approach will provide an important clue for elucidating the mechanisms underlying schizophrenia and endogenous psychiatric disorders. Next, we discuss account for the neurobiological mechanisms underlying drug dependence. The reward system in the brain, which is common for all dependent drugs, has been explained, and the stages of addiction corresponding to the development of drug dependence have been discussed followed. In addition, we have discussed the epigenetics aspects of substance dependence, which is one of the hottest topics in psychiatric genetics. We expect that further studies of the mechanisms underlying drug dependence will aid in elucidating of the pathophysiology of various psychiatric diseases. PMID- 22308262 TI - [Near-infrared spectroscopy in psychiatry]. AB - Near-infrared spectroscopy (NIRS) is a functional neuroimaging technique that has been increasingly employed in psychology and psychiatry. Because NIRS can detect only cerebral cortex reactivities with low spatial resolution and may suffer from contaminating signals from the skin and skull, its data should be interpreted as a global index of cerebral cortex reactivities. Within these limitations, the advantages of NIRS over fMRI such as complete non-invasiveness, small measurement apparatus, high time resolution, and natural examination setting, makes it the preferred method in studies of brain substrates of subjective feelings of sleepiness and fatigue, personality, conversation, and psychiatric disorders. Two thirds of the original articles on NIRS applications in psychiatry have been published by Japanese researchers. NIRS examination of psychiatric disorders using a verbal fluency task of only 3 minutes demonstrated their characteristics of frontal lobe function: depression was characterized by smaller activation, bipolar depression by comparable but delayed activation, and schizophrenia by reduced activation followed by re-activation during the post-task period. These characteristics can also be identified in individual NIRS data using 2 automatically calculated parameters. Based on these results, NIRS application in psychiatry has been approved as one of the Advanced Medical Technologies in 2009 as an aid for differential diagnosis of depressive symptoms. A lack of clinical laboratory tests for diagnosis and treatment has been one of the major difficulties for reliable diagnosis, quantitative treatment assessment, and prevention of psychiatric disorders; NIRS may be the first step toward such clinical laboratory tests in psychiatry. PMID- 22308263 TI - [Correlation between increased platelet ADP aggregability and silent brain infarcts]. AB - The purpose of this study was to investigate the correlation between platelet aggregability and silent brain infarcts. The study subjects were 445 people (264 men, 181 women; mean age, 53 +/- 14 years) with no neurologic signs, history of brain tumor, trauma, cerebrovascular disease, or antiplatelet medications. Adenosine diphosphate (ADP)-induced platelet aggregation was measured by the aggregation-size analytic method. Platelet aggregability was classified into 9 classes. The presence of headache/vertigo, hypertension, diabetes mellitus, hyperlipidemia, or smoking was elicited by questioning or blood sampling. A head MRI scan was performed, and if marked atherosclerosis or obvious stenosis in the intracranial vessels was detected, it was defined as a positive MRA finding. Silent brain infarcts were detected in 26.3% of subjects. Hyperaggregability defined as that above class 6, 7, and 8 was present in 43.8%, 30.8%, and 15.7% of subjects, respectively. The risk factors for silent brain infarcts by multiple logistic regression analysis were aging, hypertension, positive MRA findings, and hyperaggregability. Platelet ADP hyperaggregability might be a risk factor for silent brain infarcts. PMID- 22308264 TI - Altered patterns of fractionation and exon deletions in Brassica rapa support a two-step model of paleohexaploidy. AB - The genome sequence of the paleohexaploid Brassica rapa shows that fractionation is biased among the three subgenomes and that the least fractionated subgenome has approximately twice as many orthologs as its close (and relatively unduplicated) relative Arabidopsis than had either of the other two subgenomes. One evolutionary scenario is that the two subgenomes with heavy gene losses (I and II) were in the same nucleus for a longer period of time than the third subgenome (III) with the fewest gene losses. This "two-step" hypothesis is essentially the same as that proposed previously for the eudicot paleohexaploidy; however, the more recent nature of the B. rapa paleohexaploidy makes this model more testable. We found that subgenome II suffered recent small deletions within exons more frequently than subgenome I, as would be expected if the genes in subgenome I had already been near maximally fractionated before subgenome III was introduced. We observed that some sequences, before these deletions, were flanked by short direct repeats, a unique signature of intrachromosomal illegitimate recombination. We also found, through simulations, that short--single or two-gene -deletions appear to dominate the fractionation patterns in B. rapa. We conclude that the observed patterns of the triplicated regions in the Brassica genome are best explained by a two-step fractionation model. The triplication and subsequent mode of fractionation could influence the potential to generate morphological diversity--a hallmark of the Brassica genus. PMID- 22308265 TI - Reprogrammed keratinocytes from elderly type 2 diabetes patients suppress senescence genes to acquire induced pluripotency. AB - Nuclear reprogramming enables patient-specific derivation of induced pluripotent stem (iPS) cells from adult tissue. Yet, iPS generation from patients with type 2 diabetes (T2D) has not been demonstrated. Here, we report reproducible iPS derivation of epidermal keratinocytes (HK) from elderly T2D patients. Transduced with human OCT4, SOX2, KLF4 and c-MYC stemness factors under serum-free and feeder-free conditions, reprogrammed cells underwent dedifferentiation with mitochondrial restructuring, induction of endogenous pluripotency genes - including NANOG, LIN28, and TERT, and down-regulation of cytoskeletal, MHC class I- and apoptosis-related genes. Notably, derived iPS clones acquired a rejuvenated state, characterized by elongated telomeres and suppressed senescence related p15INK4b/p16INK4a gene expression and oxidative stress signaling. Stepwise guidance with lineage-specifying factors, including Indolactam V and GLP 1, redifferentiated HK-derived iPS clones into insulin-producing islet-like progeny. Thus, in elderly T2D patients, reprogramming of keratinocytes ensures a senescence-privileged status yielding iPS cells proficient for regenerative applications. PMID- 22308266 TI - microRNA-1/133a and microRNA-206/133b clusters: dysregulation and functional roles in human cancers. AB - MicroRNAs (miRNAs) are endogenous short non-coding RNA molecules that regulate gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. A growing body of evidence suggests that miRNAs are aberrantly expressed in many human cancers and that they play significant roles in the initiation, development and metastasis of human cancers. Genome-wide miRNA expression signatures provide information on the aberrant expression of miRNAs in cancers rapidly and precisely. Recently, studies from our group and others revealed that microRNA-1 (miR-1), microRNA-133a (miR-133a), microRNA-133b (miR 133b) and microRNA-206 (miR-206) are frequently downregulated in various types of cancers. Interestingly, miR-1-1/miR-133a-2, miR-1-2/miR-133a-1, and miR-206/miR 133b form clusters in three different chromosomal regions of the human genome - 20q13.33, 18q11.2 and 6p12.1, respectively. Here we review highlights of recent findings on the aberrant expression and functional significance of the miR-1/miR 133a and miR-206/miR-133b clusters in human cancers. PMID- 22308267 TI - "Picolog," a synthetically-available bryostatin analog, inhibits growth of MYC induced lymphoma in vivo. AB - Bryostatin 1 is a naturally occurring complex macrolide with potent anti neoplastic activity. However, its extremely low natural occurrence has impeded clinical advancement. We developed a strategy directed at the design of simplified and synthetically more accessible bryostatin analogs. Our lead analog, "picolog", can be step-economically produced. Picolog, compared to bryostatin, exhibited superior growth inhibition of MYC-induced lymphoma in vitro. A key mechanism of picolog's (and bryostatin's) activity is activation of PKC. A novel nano-immunoassay (NIA) revealed that picolog treatment increased phospho-MEK2 in the PKC pathway. Moreover, the inhibition of PKC abrogated picolog's activity. Finally, picolog was highly potent at 100 micrograms/kg and well tolerated at doses ranging from 100 micrograms/kg to 1 milligram/kg in vivo for the treatment of our aggressive model of MYC-induced lymphoma. We provide the first in vivo validation that the bryostatin analog, picolog, is a potential therapeutic agent for the treatment of cancer and other diseases. PMID- 22308268 TI - From the patient to the clinical mycology laboratory: how can we optimise microscopy and culture methods for mould identification? AB - The identification of fungi relies mainly on morphological criteria. However, there is a need for robust and definitive phenotypic identification procedures in order to evaluate continuously evolving molecular methods. For the future, there is an emerging consensus that a combined (phenotypic and molecular) approach is more powerful for fungal identification, especially for moulds. Most of the procedures used for phenotypic identification are based on experience rather than comparative studies of effectiveness or performance and there is a need for standardisation among mycology laboratories. This review summarises and evaluates the evidence for the major existing phenotypic identification procedures for the predominant causes of opportunistic mould infection. We have concentrated mainly on Aspergillus, Fusarium and mucoraceous mould species, as these are the most important clinically and the ones for which there are the most molecular taxonomic data. PMID- 22308269 TI - A simple technique for augmenting recovery of cellular material from fine needle aspirates for adjunctive studies. PMID- 22308270 TI - An unusual cause of ischaemic colitis. PMID- 22308271 TI - Yet another reason to treat HIV infection. PMID- 22308272 TI - Neurocognitive and motor deficits in HIV-infected Ugandan children with high CD4 cell counts. AB - BACKGROUND: Human immunodeficiency virus (HIV) infection causes neurocognitive or motor function deficits in children with advanced disease, but it is unclear whether children with CD4 cell measures above the World Health Organization (WHO) thresholds for antiretroviral therapy (ART) initiation suffer significant impairment. METHODS: The neurocognitive and motor functions of HIV-infected ART naive Ugandan children aged 6-12 years with CD4 cell counts of >350 cells/MUL and CD4 cell percentage of >15% were compared with those of HIV-uninfected children, using the Test of Variables of Attention (TOVA), the Kaufman Assessment Battery for Children, second edition (KABC-2), and the Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT-2). RESULTS: Ninety-three HIV-infected children (median CD4 cell count, 655 cells/MUL; plasma HIV RNA level, 4.7 log(10) copies/mL) were compared to 106 HIV-uninfected children. HIV-infected children performed worse on TOVA visual reaction times (multivariate analysis of covariance; P = .006); KABC-2 sequential processing (P = .005), simultaneous processing (P = .039), planning/reasoning (P = .023), and global performance (P = .024); and BOT-2 total motor proficiency (P = .003). High plasma HIV RNA level was associated with worse performance in 10 cognitive measures and 3 motor measures. In analysis of only WHO clinical stage 1 or 2 HIV-infected children (n = 68), significant differences between the HIV-infected and HIV-uninfected groups (P < .05) remained for KABC-2 sequential processing, KABC-2 planning/reasoning, and BOT-2 motor proficiency. CONCLUSIONS: Significant motor and cognitive deficits were found in HIV-infected ART-naive Ugandan children with CD4 cell counts of ~350 cells/MUL and percentages of >15%. Study of whether early initiation of ART could prevent or reverse such deficits is needed. PMID- 22308274 TI - Comparison of exercise treadmill testing with cardiac computed tomography angiography among patients presenting to the emergency room with chest pain: the Rule Out Myocardial Infarction Using Computer-Assisted Tomography (ROMICAT) study. AB - BACKGROUND: The aims of our study were to (1) examine how data from exercise treadmill testing (ETT) can identify patients who have coronary plaque or stenosis, using CT angiography (CTA) as the reference standard, and (2) identify patient characteristics that may be used in selecting ETT versus CTA. METHODS AND RESULTS: The Rule Out Myocardial Infarction Using Computer-Assisted Tomography (ROMICAT) trial was an observational cohort study of acute chest pain patients presenting to the emergency department with normal initial troponin and a nonischemic ECG. Univariate and multivariable analyses were performed to assess the relationship of baseline clinical data and ETT parameters with coronary plaque and stenosis on CTA. Of the 220 patients who had ETT (mean age, 51 years; 63% men), 21 (10%) had positive results. A positive ETT had a sensitivity of 30% and specificity of 93% to detect >50% stenosis. The sensitivity increased to 83% after excluding uninterpretable segments and evaluating the ability to detect a >70% stenosis. Predictors of plaque included older age, male sex, diabetes, hypertension, hyperlipidemia, lower functional capacity, and a lower Duke Treadmill Score. Both a positive ETT and a low Duke Treadmill Score were significant univariate and multivariable predictors of stenosis >50% on CTA Whereas the prevalence of stenosis by CTA was greater among patients with more risk factors, coronary stenosis was not present among men <40 years old or women <50 years old or individuals who achieved at least 13 metabolic equivalents on ETT. CONCLUSIONS: Among low- to intermediate-risk patients with acute chest pain, a positive ETT has a limited sensitivity but high specificity for the detection of >50% stenosis by CTA. Although patients with a high number of clinical risk factors are more likely to have obstructive coronary artery disease, those who are young or who would be expected to have a very high exercise capacity are unlikely to have coronary stenosis and therefore may benefit from initial ETT testing instead of CTA. PMID- 22308275 TI - Cocktail of eternity: HDAC meets miR. AB - In this issue of Blood, Sampath and colleagues provide an important missing link in how microRNAs (miRs) can be silenced in chronic lymphocytic leukemia (CLL):histone deacetylases (HDACs) that are overexpressed in CLL block critical miRs in the malignant B cell resulting in pro-survival signals. Thus,HDAC inhibition is an attractive new therapeutic strategy in CLL. PMID- 22308276 TI - A JAK-in-the-cell cycle. AB - In this issue of Blood, Gautier and colleagues describe a novel signaling pathway in which deregulated JAK2 activity augments expression of a key regulator of the cell cycle, the CDC25A phosphatase, via a translational mechanism. PMID- 22308277 TI - Polycomb segment myeloid malignancies. AB - An unexpected revelation of cancer genome studies has been frequent abnormality in genes for factors that modify chromatin, underscored in this issue of Blood by reports from Score et al and Kroeze et al of inactivating mutations and chromosome loss in SUZ12, EED and JARID2 in myelodysplastic syndrome (MDS) and myeloproliferative disease (MPD). PMID- 22308278 TI - HIT: treatment easier, prevention harder. AB - In this issue of Blood, Krauel and colleagues identify two potential off-label treatments(rivaroxaban, dabigatran) for heparin-induced thrombocytopenia (HIT),and also outline aHIT prevention strategy through disrupting PF4/heparin complexes with low-sulfated heparin; the former approach will be easy to implement, the latter much harder-but potentially more worthwhile PMID- 22308279 TI - Toddy for chilled platelets? AB - In this issue of Blood, Jansen and colleagues use murine models to give new insights into the possible mechanisms of clearance of transfused refrigerated platelets. PMID- 22308280 TI - Control of GVHD: it's in our DNA! AB - Selective depletion of the alloreactive T cells causing graft-versus-host disease (GVHD) without loss of the graft-versus-leukemia (GVL) effect is the holy grail of hematopoietic cell transplantation (HCT). In this issue of Blood, He et al demonstrate that inhibition of histone methylation leads to selective apoptosis of the alloreactive effector cells. Moreover, they demonstrate that this inhibition of histone methylation remarkably stops ongoing GVHD. PMID- 22308281 TI - TM hidden treasure: lectin-like domain. AB - In this issue of Blood, Kuo et al have used recombinant lectin-like domain of thrombomodulin domain 1 (TMD1) to demonstrate the action of lectin-like domain in blocking Lewis Y antigen (LeY)-mediated angiogenesis and control of tumor growth. PMID- 22308282 TI - Lack of Foxp3+ macrophages in both untreated and B16 melanoma-bearing mice. PMID- 22308283 TI - Macrophages have no lineage history of Foxp3 expression. PMID- 22308284 TI - Genetic defects in PRC2 components other than EZH2 are not common in myeloid malignancies. PMID- 22308285 TI - Bcl-xL-inhibitory BH3 mimetics (ABT-737 or ABT-263) and the modulation of cytosolic calcium flux and platelet function. PMID- 22308286 TI - Doubts concerning functional endothelial nitric oxide synthase in human erythrocytes. PMID- 22308287 TI - Risk prediction for early in-hospital mortality following heart transplantation in the United States. AB - BACKGROUND: Risk factors for early mortality after heart transplant (HT) have not been used for quantitative risk prediction. We sought to develop and validate a risk prediction model for posttransplant in-hospital mortality in HT recipients. METHODS AND RESULTS: We derived the model in subjects aged >=18 years who underwent primary HT in the United States from January 2007 to June 2009 (n=4248) and validated it internally using a bootstrapping technique (200 random samples, n=4248). We then assessed the model's performance in patients receiving an HT from July 2009 to October 2010 (external validation cohort, n=2346). Posttransplant in-hospital mortality was 4.7% in the model derivation cohort. The best-fitting model based on recipient characteristics at transplant had 6 variables: age, diagnosis, type of mechanical support, ventilator support, estimated glomerular filtration rate, and total serum bilirubin. Model discrimination for survivors versus nonsurvivors was acceptable during derivation and internal validation (C statistic, 0.722 and 0.731, respectively) as was model calibration during derivation (Hosmer Lemeshow [HL] P=0.47). Model performance was reasonable in the external validation cohort (predicted mortality, 4.9%; actual mortality, 4.3%; R(2)=0.95; C statistic, 0.68; HL P=0.48). Adding the donor-related variables of age and ischemic time to the model improved its performance in both the model derivation (C statistic, 0.742; HL P=0.70) and the external validation (C statistic, 0.695; HL P=0.42) cohorts. CONCLUSIONS: The proposed model allows risk stratification of HT candidates for early posttransplant mortality and may be useful in counseling patients with regard to their posttransplant prognosis. The model with additional donor-related variables may be useful during donor selection. PMID- 22308288 TI - CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: pilot clinical trial results. AB - Cellular immune responses have the potential to elicit dramatic and sustained clinical remissions in lymphoma patients. Recent clinical trial data demonstrate that modification of T cells with chimeric antigen receptors (CARs) is a promising strategy. T cells containing CARs with costimulatory domains exhibit improved activity against tumors. We conducted a pilot clinical trial testing a "third-generation" CD20-specific CAR with CD28 and 4-1BB costimulatory domains in patients with relapsed indolent B-cell and mantle cell lymphomas. Four patients were enrolled, and 3 received T-cell infusions after cyclophosphamide lymphodepletion. Treatment was well tolerated, although one patient developed transient infusional symptoms. Two patients without evaluable disease remained progression-free for 12 and 24 months. The third patient had an objective partial remission and relapsed at 12 months after infusions. Modified T cells were detected by quantitative PCR at tumor sites and up to 1 year in peripheral blood, albeit at low levels. No evidence of host immune responses against infused cells was detected. In conclusion, adoptive immunotherapy with CD20-specific T cells was well tolerated and was associated with antitumor activity. We will pursue alternative gene transfer technologies and culture conditions in future studies to improve CAR expression and cell production efficiency. PMID- 22308289 TI - Long-term outcomes after transplantation of HLA-identical related G-CSF-mobilized peripheral blood mononuclear cells versus bone marrow. AB - Between 1996 and 1999, 172 patients (median age, 42 years) with hematologic malignancies were randomly assigned to receive either HLA-identical related bone marrow or G-CSF-mobilized peripheral blood mononuclear cells (G-PBMCs) after myeloablative conditioning. Early results showed that transplantation of G-PBMCs, compared with marrow, was associated with significantly superior 2-year disease free survival (DFS) and overall survival. Ten-year follow-up showed a sustained DFS benefit associated with G-PBMCs (mortality or relapse hazard ratio, 0.64; 95% confidence interval, 0.4-1.0; P = .03), although the likelihood of overall survival was not significantly different between the 2 groups (mortality hazard ratio, 0.75; 95% confidence interval, 0.5-1.2; P = .20). The 10-year cumulative incidence of chronic GVHD and the duration of systemic immunosuppression were similar in the 2 groups. In summary, transplantation of HLA-identical related G PBMCs, compared with marrow, was associated with superior short-term and long term DFS, and there was no evidence that this benefit was outweighed by GVHD related late mortality. PMID- 22308290 TI - Terminal transport of lytic granules to the immune synapse is mediated by the kinesin-1/Slp3/Rab27a complex. AB - Cytotoxic T lymphocytes kill target cells via the polarized secretion of cytotoxic granules at the immune synapse. The lytic granules are initially recruited around the polarized microtubule-organizing center. In a dynein dependent transport process, the granules move along microtubules toward the microtubule-organizing center in the minus-end direction. Here, we found that a kinesin-1-dependent process is required for terminal transport and secretion of polarized lytic granule to the immune synapse. We show that synaptotagmin-like protein 3 (Slp3) is an effector of Rab27a in cytotoxic T lymphocytes and interacts with kinesin-1 through the tetratricopeptide repeat of the kinesin-1 light chain. Inhibition of the Rab27a/Slp3/kinesin-1 transport complex impairs lytic granule secretion. Our data provide further molecular insights into the key functional and regulatory mechanisms underlying the terminal transport of cytotoxic granules and the latter's secretion at the immune synapse. PMID- 22308291 TI - Hematopoietic stem cells: to be or Notch to be. AB - Notch is a well-conserved signaling pathway and its function in cell fate determination is crucial in embryonic development and in the maintenance of tissue homeostasis during adult life. Notch activation depends on cell-cell interactions that are essential for the generation of cell diversity from initially equivalent cell populations. In the adult hematopoiesis, Notch is undoubtedly a very efficient promoter of T-cell differentiation, and this has masked for a long time the effects of Notch on other blood lineages, which are gradually being identified. However, the adult hematopoietic stem cell (HSC) remains mostly refractory to Notch intervention in experimental systems. In contrast, Notch is essential for the generation of the HSCs, which takes place during embryonic development. This review summarizes the knowledge accumulated in recent years regarding the role of the Notch pathway in the different stages of HSC ontology from embryonic life to fetal and adult bone marrow stem cells. In addition, we briefly examine other systems where Notch regulates specific stem cell capacities, in an attempt to understand how Notch functions in stem cell biology. PMID- 22308293 TI - Disruption of BIRC3 associates with fludarabine chemorefractoriness in TP53 wild type chronic lymphocytic leukemia. AB - The genetic lesions identified to date do not fully recapitulate the molecular pathogenesis of chronic lymphocytic leukemia (CLL) and do not entirely explain the development of severe complications such as chemorefractoriness. In the present study, BIRC3, a negative regulator of noncanonical NF-kappaB signaling, was investigated in different CLL clinical phases. BIRC3 lesions were absent in monoclonal B-cell lymphocytosis (0 of 63) and were rare in CLL at diagnosis (13 of 306, 4%). Conversely, BIRC3 disruption selectively affected 12 of 49 (24%) fludarabine-refractory CLL cases by inactivating mutations and/or gene deletions that distributed in a mutually exclusive fashion with TP53 abnormalities. In contrast to fludarabine-refractory CLL, progressive but fludarabine-sensitive patients were consistently devoid of BIRC3 abnormalities, suggesting that BIRC3 genetic lesions associate specifically with a chemorefractory phenotype. By actuarial analysis in newly diagnosed CLL (n = 306), BIRC3 disruption identified patients with a poor outcome similar to that associated with TP53 abnormalities and exerted a prognostic role that was independent of widely accepted clinical and genetic risk factors. Consistent with the role of BIRC3 as a negative regulator of NF-kappaB, biochemical studies revealed the presence of constitutive noncanonical NF-kappaB activation in fludarabine-refractory CLL patients harboring molecular lesions of BIRC3. These data identify BIRC3 disruption as a recurrent genetic lesion of high-risk CLL devoid of TP53 abnormalities. PMID- 22308294 TI - Retrospective analysis of prognostic factors for angioimmunoblastic T-cell lymphoma: a multicenter cooperative study in Japan. AB - Angioimmunoblastic T-cell lymphoma (AITL) is a major type of peripheral T-cell lymphoma (PTCL). To elucidate the clinicopathologic characteristics and prognosis of AITL in Japan, we retrospectively analyzed 207 patients with AITL. The median patient age was 67 years (range, 34-91 years), with 73% of patients older than 60 years. With a median follow-up of 42 months in surviving patients, 3-year overall survival (OS) was 54% and progression-free survival (PFS) was 38%. The International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT) were predictive for OS in this analysis. Multivariate analysis found that age older than 60 years, elevated white blood cell (WBC) and IgA levels, the presence of anemia and thrombocytopenia, and extranodal involvement at > 1 site were significant prognostic factors for OS, and IgA, anemia, and mediastinal lymphadenopathy were significant prognostic factors for PFS. A novel prognostic model consisting of the prognostic factors for OS was successfully constructed. In conclusion, IPI and PIT were still useful for prognostication of AITL, and other factors, including those not used in IPI, such as IgA, anemia, WBC count, thrombocytopenia, and mediastinal lymphadenopathy, also significantly affected prognosis. Future investigations for IgA as a unique prognostic factor are warranted. PMID- 22308292 TI - Transplantation in patients with SCID: mismatched related stem cells or unrelated cord blood? AB - Pediatric patients with SCID constitute medical emergencies. In the absence of an HLA-identical hematopoietic stem cell (HSC) donor, mismatched related-donor transplantation (MMRDT) or unrelated-donor umbilical cord blood transplantation (UCBT) are valuable treatment options. To help transplantation centers choose the best treatment option, we retrospectively compared outcomes after 175 MMRDTs and 74 UCBTs in patients with SCID or Omenn syndrome. Median follow-up time was 83 months and 58 months for UCBT and MMRDT, respectively. Most UCB recipients received a myeloablative conditioning regimen; most MMRDT recipients did not. UCB recipients presented a higher frequency of complete donor chimerism (P = .04) and faster total lymphocyte count recovery (P = .04) without any statistically significance with the preparative regimen they received. The MMRDT and UCBT groups did not differ in terms of T-cell engraftment, CD4(+) and CD3(+) cell recoveries, while Ig replacement therapy was discontinued sooner after UCBT (adjusted P = .02). There was a trend toward a greater incidence of grades II-IV acute GVHD (P = .06) and more chronic GVHD (P = .03) after UCBT. The estimated 5 year overall survival rates were 62% +/- 4% after MMRDT and 57% +/- 6% after UCBT. For children with SCID and no HLA-identical sibling donor, both UCBT and MMRDT represent available HSC sources for transplantation with quite similar outcomes. PMID- 22308295 TI - A phase 1/2 study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia. AB - The interaction of acute myeloid leukemia (AML) blasts with the leukemic microenvironment is postulated to be an important mediator of resistance to chemotherapy and disease relapse. We hypothesized that inhibition of the CXCR4/CXCL12 axis by the small molecule inhibitor, plerixafor, would disrupt the interaction of leukemic blasts with the environment and increase the sensitivity of AML blasts to chemotherapy. In this phase 1/2 study, 52 patients with relapsed or refractory AML were treated with plerixafor in combination with mitoxantrone, etoposide, and cytarabine. In phase 1, plerixafor was escalated to a maximum of 0.24 mg/kg/d without any dose-limiting toxicities. In phase 2, 46 patients were treated with plerixafor 0.24 mg/kg/d in combination with chemotherapy with an overall complete remission and complete remission with incomplete blood count recovery rate (CR + CRi) of 46%. Correlative studies demonstrated a 2-fold mobilization in leukemic blasts into the peripheral circulation. No evidence of symptomatic hyperleukocytosis or delayed count recovery was observed with the addition of plerixafor. We conclude that the addition of plerixafor to cytotoxic chemotherapy is feasible in AML, and results in encouraging rates of remission with correlative studies demonstrating in vivo evidence of disruption of the CXCR4/CXCL12 axis. PMID- 22308297 TI - Socio-economic inequalities in healthy child development: the evidence grows. PMID- 22308296 TI - HIF-1alpha deletion partially rescues defects of hematopoietic stem cell quiescence caused by Cited2 deficiency. AB - Cited2 is a transcriptional modulator involved in various biologic processes including fetal liver hematopoiesis. In the present study, the function of Cited2 in adult hematopoiesis was investigated in conditional knockout mice. Deletion of Cited2 using Mx1-Cre resulted in increased hematopoietic stem cell (HSC) apoptosis, loss of quiescence, and increased cycling, leading to a severely impaired reconstitution capacity as assessed by 5-fluorouracil treatment and long term transplantation. Transcriptional profiling revealed that multiple HSC quiescence- and hypoxia-related genes such as Egr1, p57, and Hes1 were affected in Cited2-deficient HSCs. Because Cited2 is a negative regulator of HIF-1, which is essential for maintaining HSC quiescence, and because we demonstrated previously that decreased HIF-1alpha gene dosage partially rescues both cardiac and lens defects caused by Cited2 deficiency, we generated Cited2 and HIF-1alpha double-knockout mice. Additional deletion of HIF-1alpha in Cited2-knockout BM partially rescued impaired HSC quiescence and reconstitution capacity. At the transcriptional level, deletion of HIF-1alpha restored expression of p57 and Hes1 but not Egr1 to normal levels. Our results suggest that Cited2 regulates HSC quiescence through both HIF-1-dependent and HIF-1-independent pathways. PMID- 22308298 TI - Cost-effectiveness of transcatheter aortic valve replacement. PMID- 22308299 TI - Cost-effectiveness of transcatheter aortic valve replacement compared with standard care among inoperable patients with severe aortic stenosis: results from the placement of aortic transcatheter valves (PARTNER) trial (Cohort B). AB - BACKGROUND: In patients with severe aortic stenosis who cannot have surgery, transcatheter aortic valve replacement (TAVR) has been shown to improve survival and quality of life compared with standard therapy, but the costs and cost effectiveness of this strategy are not yet known. METHODS AND RESULTS: The PARTNER trial randomized patients with symptomatic, severe aortic stenosis who were not candidates for surgery to TAVR (n=179) or standard therapy (n=179). Empirical data regarding survival, quality of life, medical resource use, and hospital costs were collected during the trial and used to project life expectancy, quality-adjusted life expectancy, and lifetime medical care costs to estimate the incremental cost-effectiveness of TAVR from a US perspective. For patients treated with TAVR, mean costs for the initial procedure and hospitalization were $42 806 and $78 542, respectively. Follow-up costs through 12 months were lower with TAVR ($29 289 versus $53 621) because of reduced hospitalization rates, but cumulative 1-year costs remained higher ($106 076 versus $53 621). We projected that over a patient's lifetime, TAVR would increase discounted life expectancy by 1.6 years (1.3 quality-adjusted life-years) at an incremental cost of $79 837. The incremental cost-effectiveness ratio for TAVR was thus estimated at $50 200 per year of life gained or $61 889 per quality adjusted life-year gained. These results were stable across a broad range of uncertainty and sensitivity analyses. CONCLUSIONS: For patients with severe aortic stenosis who are not candidates for surgery, TAVR increases life expectancy at an incremental cost per life-year gained well within accepted values for commonly used cardiovascular technologies. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894. PMID- 22308300 TI - Prognostic values of clockwise and counterclockwise rotation for cardiovascular mortality in Japanese subjects: a 24-year follow-up of the National Integrated Project for Prospective Observation of Noncommunicable Disease and Its Trends in the Aged, 1980-2004 (NIPPON DATA80). AB - BACKGROUND: Although clockwise rotation and counterclockwise rotation are distinct findings of the ECG, their prognostic significance is rarely studied. METHODS AND RESULTS: We studied prognostic values of clockwise and counterclockwise rotation on total, cardiovascular disease (CVD), and subtype mortality using the National Integrated Project for Prospective Observation of Noncommunicable Disease and Its Trends in the Aged, 1980-2004 (NIPPON DATA80) database with a 24-year follow-up. At baseline in 1980, data were collected on study participants aged >=30 years from randomly selected areas in Japan. We followed 9067 participants (44% men; mean age, 51 years). During the 24-year follow-up, mortality was as follows: 2581 total, 887 CVD, 179 coronary heart disease, 173 heart failure, and 411 stroke. The multivariate-adjusted hazard ratio (HR) with the use of the Cox model including biochemical and other ECG variables revealed that clockwise rotation was significantly positively associated with heart failure in men and women combined (HR=1.79; 95% confidence interval [CI], 1.13-2.83; P=0.013), CVD in men and in men and women combined (HR=1.49; 95% CI, 1.12-1.98; P=0.007 in men; HR=1.28; 95% CI, 1.02-1.59; P=0.030 in combined), and total mortality in men and in men and women combined (HR=1.19; 95% CI, 1.00-1.49; P=0.0496 in men; HR=1.15; 95% CI, 1.00-1.32; P=0.045 in combined). Counterclockwise rotation was significantly inversely associated stroke in men and women combined (HR=0.77; 95% CI, 0.62-0.96; P=0.017), CVD in men and in men and women combined (HR=0.74; 95% CI, 0.59-0.94; P=0.011 in men; HR=0.81; 95% CI, 0.70-0.94; P=0.006 in combined), and total mortality in women (HR=0.87; 95% CI, 0.77-0.98; P=0.023). CONCLUSIONS: We found a significant positive association of clockwise rotation and a significant inverse association of counterclockwise rotation with CVD mortality in men and in men and women combined, independent of confounding factors including other ECG changes. PMID- 22308301 TI - Randomized comparison of everolimus-eluting and sirolimus-eluting stents in patients treated with percutaneous coronary intervention: the Scandinavian Organization for Randomized Trials with Clinical Outcome IV (SORT OUT IV). AB - BACKGROUND: Among drug-eluting stents released to date, the sirolimus-eluting stent has demonstrated the least amount of late lumen loss, but its efficacy and safety have not been compared head-to-head with the next-generation everolimus eluting stent. METHODS AND RESULTS: The Scandinavian Organization for Randomized Trials with Clinical Outcome IV (SORT OUT IV) trial was a randomized multicenter, single-blind, all-comer, 2-arm, noninferiority trial comparing the everolimus eluting stent with the sirolimus-eluting stent in patients with coronary artery disease. The primary end point was a composite of safety (cardiac death, myocardial infarction, definite stent thrombosis) and efficacy (target vessel revascularization) parameters. The noninferiority criterion was a risk difference of 0.015. Intention-to-treat analyses were done at 9- and 18-month follow-ups. A total of 1390 patients were assigned to receive the everolimus-eluting stent and 1384 patients to the sirolimus-eluting stent. At the 9-month follow-up, 68 patients (4.9%) treated with the everolimus-eluting stent compared with 72 patients (5.2%) treated with the sirolimus-eluting stent experienced the primary end point (hazard ratio, 0.94; 95% confidence interval, 0.67-1.31; P for noninferiority=0.01). At the 18-month follow-up, this differential remained: 99 patients (7.2%) treated with the everolimus-eluting stent versus 105 (7.6%) treated with the sirolimus-eluting stent (hazard ratio, 0.94; 95% confidence interval, 0.71-1.23). At the 9-month follow-up, the rate of definite stent thrombosis was higher in the sirolimus-eluting group (2 patients [0.1%] versus 9 patients [0.7%]; hazard ratio, 0.22; 95% confidence interval, 0.05-1.02). At the 18-month follow-up, this difference was sustained (3 patients [0.2%] versus 12 patients [0.9%]; hazard ratio, 0.25; 95% confidence interval, 0.07-0.88). CONCLUSION: The everolimus-eluting stent was found to be noninferior to the sirolimus-eluting stent. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00552877. PMID- 22308302 TI - Regulatory role of dendritic cells in postinfarction healing and left ventricular remodeling. AB - BACKGROUND: Inflammation and immune responses are integral components in the healing process after myocardial infarction. We previously reported dendritic cell (DC) infiltration in the infarcted heart; however, the precise contribution of DC in postinfarction healing is unclear. METHODS AND RESULTS: Bone marrow cells from CD11c-diphtheria toxin receptor/green fluorescent protein transgenic mice were transplanted into lethally irradiated wild-type recipient mice. After reconstitution of bone marrow-derived cells, the recipient mice were treated with either diphtheria toxin (DC ablation) or vehicle (control), and myocardial infarction was created by left coronary ligation. CD11c(+) green fluorescent protein-positive DCs expressing CD11b and major histocompatibility complex class II were recruited into the heart, peaking on day 7 after myocardial infarction in the control group. Mice with DC ablation for 7 days showed deteriorated left ventricular function and remodeling. The DC-ablated group demonstrated enhanced and sustained expression of inflammatory cytokines such as interleukin-1beta, interleukin-18, and tumor necrosis factor-alpha, prolonged extracellular matrix degradation associated with a high level of matrix metalloproteinase-9 activity, and diminished expression level of interleukin-10 and endothelial cell proliferation after myocardial infarction compared with the control group. In vivo analyses revealed that DC-ablated infarcts had enhanced monocyte/macrophage recruitment. Among these cells, marked infiltration of proinflammatory Ly6C(high) monocytes and F4/80(+) CD206(-) M1 macrophages and, conversely, impaired recruitment of anti-inflammatory Ly6C(low) monocytes and F4/80(+) CD206(+) M2 macrophages in the infarcted myocardium were identified in the DC-ablated group compared with the control group. CONCLUSIONS: These results suggest that the DC is a potent immunoprotective regulator during the postinfarction healing process via its control of monocyte/macrophage homeostasis. PMID- 22308303 TI - Genetic mapping a meiotic driver that causes sex ratio distortion in the mosquito Aedes aegypti. AB - An endogenous meiotic driver in the dengue and yellow fever vector mosquito Aedes aegypti can cause highly male-biased sex ratio distortion in crosses from suitable genetic backgrounds. We previously selected a strain that carries a strong meiotic drive gene (D) linked with the male-determining allele (M) on chromosome 1 in A. aegypti. Here, we performed segregation analysis of the M(D) locus among backcross (BC(1)) progeny from a driver male and drive-sensitive females. Assessment of sex ratios among BC(2) progeny showed ~5.2% recombination between the M(D) locus and the sex determination locus. Multipoint linkage mapping across this region revealed consistent marker orders and recombination frequencies with the existing reference linkage map and placed the M(D) locus within a 6.5-cm interval defined by the LF159 locus and microsatellite marker 446GAA, which should facilitate future positional cloning efforts. PMID- 22308304 TI - Gaining confidence in high-throughput screening. PMID- 22308305 TI - How many great earthquakes should we expect? PMID- 22308306 TI - Factor VII-activating protease is activated in multiple trauma patients and generates anaphylatoxin C5a. AB - Severe tissue injury results in early activation of serine protease systems including the coagulation and complement cascade. In this context, little is known about factor VII-activating protease (FSAP), which is activated by substances released from damaged cells such as histones and nucleosomes. Therefore, we have measured FSAP activation in trauma patients and have identified novel FSAP substrates in human plasma. Mass spectrometry-based methods were used to identify FSAP binding proteins in plasma. Anaphylatoxin generation was measured by ELISA, Western blotting, protein sequencing, and chemotaxis assays. Plasma samples from trauma patients were analyzed for FSAP Ag and activity, nucleosomes, C5a, and C3a. Among others, we found complement components C3 and C5 in FSAP coimmunoprecipitates. C3 and C5 were cleaved by FSAP in a dose- and time-dependent manner generating functional C3a and C5a anaphylatoxins. Activation of endogenous FSAP in plasma led to increased C5a generation, but this was not the case in plasma of a homozygous carrier of Marburg I single nucleotide polymorphism with lower FSAP activity. In multiple trauma patients there was a large increase in circulating FSAP activity and nucleosomes immediately after the injury. A high correlation between FSAP activity and C5a was found. These data suggest that activation of FSAP by tissue injury triggers anaphylatoxin generation and thereby modulates the posttraumatic inflammatory response in vivo. A strong link between C5a, nucleosomes, and FSAP activity indicates that this new principle might be important in the regulation of inflammation. PMID- 22308307 TI - Derivation and maintenance of virtual memory CD8 T cells. AB - Memory CD8(+) T cells are an important component of the adaptive immune response against many infections, and understanding how Ag-specific memory CD8(+) T cells are generated and maintained is crucial for the development of vaccines. We recently reported the existence of memory-phenotype, Ag-specific CD8(+) T cells in unimmunized mice (virtual memory or VM cells). However, it was not clear when and where these cells are generated during normal development, nor the factors required for their production and maintenance. This issue is especially pertinent given recent data showing that memory-like CD8 T cells can be generated in the thymus, in a bystander response to IL-4. In this study, we show that the size of the VM population is reduced in IL-4R-deficient animals. However, the VM population appears first in the periphery and not the thymus of normal animals, suggesting this role of IL-4 is manifest following thymic egress. We also show that the VM pool is durable, showing basal proliferation and long-term maintenance in normal animals, and also being retained during responses to unrelated infection. PMID- 22308308 TI - A novel NKR-P1B(bright) NK cell subset expresses an activated CD25(+)CX(3)CR1(+)CD62L(-)CD11b(-)CD27(-) phenotype and is prevalent in blood, liver, and gut-associated lymphoid organs of rats. AB - The inhibitory NKR-P1B receptor identifies a subset of rat splenic NK cells that is low in Ly49 receptors but enriched for CD94/NKG2 receptors. We report in this study a novel NKR-P1B(bright) NK subpopulation that is prevalent in peripheral blood, liver, and gut-associated lymphoid organs and scarce in the spleen, peripheral lymph nodes, bone marrow, and lungs. This NKR-P1B(bright) NK subset displays an activated phenotype, expressing CD25, CD93, CX(3)CR1 and near absence of CD62-L, CD11b, and CD27. Functionally, NKR-P1B(bright) NK cells are highly responsive in terms of IFN-gamma production and exert potent cytolytic activity. They show little spontaneous proliferation, are reduced in numbers upon in vivo activation with polyinosinic:polycytidylic acid, and have poor survival in ex vivo cytokine cultures. Our findings suggest that NKR-P1B(bright) NK cells are fully differentiated effector cells that rapidly die upon further activation. The identification of this novel rat NK cell subset may facilitate future translational research of the role of distinct NK cell subsets under normal physiological conditions and during ongoing immune responses. PMID- 22308309 TI - Tyrosine phosphorylation-independent regulation of lipopolysaccharide-mediated response by the transmembrane adaptor protein LAB. AB - Linker for activation of B cells (LAB)/non-T cell activation linker is a transmembrane adaptor protein that functions in immunoreceptor-mediated signaling. Published studies have shown that LAB has both positive and negative roles in regulating TCR and high-affinity Fc receptor-mediated signaling and cellular function. In this study, we showed that LAB was also expressed in dendritic cells and that LAB deficiency affected LPS-mediated signaling and cytokine production. LPS-mediated MAPK activation was enhanced in LAB(-/-) bone marrow-derived dendritic cells. These bone marrow-derived dendritic cells also produced more TNF-alpha, IL-6, and IL-10 than wild-type cells. Moreover, LAB(-/-) mice were hyperresponsive to LPS-induced septic shock. These data indicated that LAB has a negative role in LPS-mediated responses. By using LAB knockin mice, which harbor mutations at five membrane-distal tyrosines, we further showed that, in contrast to its role in immunoreceptor-mediated signaling, LAB function in LPS mediated signaling pathway did not depend on its tyrosine phosphorylation. Our study suggested a novel mechanism by which LAB functions in the regulation of innate immunity. PMID- 22308310 TI - Removal of syndecan-1 promotes TRAIL-induced apoptosis in myeloma cells. AB - Syndecan is the major transmembrane proteoglycan in cells. Of the four syndecans, syndecan-1 is the dominant form expressed in multiple myeloma and is an indicator of poor prognosis. In the current study, we observed that early TRAIL-induced apoptotic processes were accompanied by cleavage of syndecan-1 intracellular region, and explored the possibility whether removal of syndecan-1 promotes apoptotic processes. We found that syndecan-1 knockdown by specific small interfering RNA in multiple myeloma enhanced TRAIL-induced apoptosis, even though the expression of TRAIL receptors and several apoptosis-associated molecules was unaffected. The enhanced TRAIL-mediated apoptosis in syndecan-1-deficient cells was not due to a decrease in surface heparan sulfate or a reduction in TRAIL receptor endocytosis. The increase in TRAIL-induced cell death was accompanied by an elevated caspase-8 activation and an enhanced formation of death-inducing signaling complexes, which could be attributed to an increased expression of TRAIL receptor O-glycosylation enzyme in syndecan-1-deficient cells. We also found that in H9 lymphoma and Jurkat cells, knockdown of the predominant syndecan member also led to an increase in Fas ligand-induced apoptosis. Our results demonstrate that syndecan plays a negative role in death receptor-mediated cell death, suggesting potential application of syndecan downregulation in the treatment of myeloma in combination with TRAIL. PMID- 22308311 TI - Recognition and prevention of tumor metastasis by the NK receptor NKp46/NCR1. AB - NK cells employ a variety of activating receptors to kill virally infected and tumor cells. Prominent among these receptors are the natural cytotoxicity receptors (NCRs) (NKp30, NKp44, and NKp46), of which only NKp46 has a mouse ortholog (NCR1). The tumor ligand(s) of NKp46/NCR1 is still unknown, but it was shown that the human NKp46 and the mouse NCR1 are involved in tumor eradication both in vitro and in vivo. Whether any of the NK activating receptors is involved in the prevention of tumor metastasis is unknown. To address this question, we studied the activity of the NK cell receptor NKp46/NCR1 in two spontaneous metastasis models, the B16F10.9 melanoma (B16) and the Lewis lung carcinoma (D122) in the NCR1 knockout mouse that was generated by our group, in various in vitro and in vivo assays. We demonstrated that all B16 and D122 tumors, including those generated in vivo, express an unknown ligand(s) for NKp46/NCR1. We have characterized the properties of the NKp46/NCR1 ligand(s) and demonstrated that NKp46/NCR1 is directly involved in the killing of B16 and D122 cells. Importantly, we showed in vivo that NKp46/NCR1 plays an important role in controlling B16 and D122 metastasis. Thus, to our knowledge, in this study we provide the first evidence for the direct involvement of a specific NK killer receptor in preventing tumor metastasis. PMID- 22308312 TI - Chronic shift-lag alters the circadian clock of NK cells and promotes lung cancer growth in rats. AB - Prolonged subjection to unstable work or lighting schedules, particularly in rotating shift-workers, is associated with an increased risk of immune-related diseases, including several cancers. Consequences of chronic circadian disruption may also extend to the innate immune system to promote cancer growth, as NK cell function is modulated by circadian mechanisms and plays a key role in lysis of tumor cells. To determine if NK cell function is disrupted by a model of human shift-work and jet-lag, Fischer (344) rats were exposed to either a standard 12:12 light-dark cycle or a chronic shift-lag paradigm consisting of 10 repeated 6-h photic advances occurring every 2 d, followed by 5-7 d of constant darkness. This model resulted in considerable circadian disruption, as assessed by circadian running-wheel activity. NK cells were enriched from control and shifted animals, and gene, protein, and cytolytic activity assays were performed. Chronic shift-lag altered the circadian expression of clock genes, Per2 and Bmal1, and cytolytic factors, perforin and granzyme B, as well as the cytokine, IFN-gamma. These alterations were correlated with suppressed circadian expression of NK cytolytic activity. Further, chronic shift-lag attenuated NK cell cytolytic activity under stimulated in vivo conditions, and promoted lung tumor growth following i.v. injection of MADB106 tumor cells. Together, these findings suggest chronic circadian disruption promotes tumor growth by altering the circadian rhythms of NK cell function. PMID- 22308313 TI - Assessing the impacts of livestock production on biodiversity in rangeland ecosystems. AB - Biodiversity in rangelands is decreasing, due to intense utilization for livestock production and conversion of rangeland into cropland; yet the outlook of rangeland biodiversity has not been considered in view of future global demand for food. Here we assess the impact of future livestock production on the global rangelands area and their biodiversity. First we formalized existing knowledge about livestock grazing impacts on biodiversity, expressed in mean species abundance (MSA) of the original rangeland native species assemblages, through metaanalysis of peer-reviewed literature. MSA values, ranging from 1 in natural rangelands to 0.3 in man-made grasslands, were entered in the IMAGE-GLOBIO model. This model was used to assess the impact of change in food demand and livestock production on future rangeland biodiversity. The model revealed remarkable regional variation in impact on rangeland area and MSA between two agricultural production scenarios. The area of used rangelands slightly increases globally between 2000 and 2050 in the baseline scenario and reduces under a scenario of enhanced uptake of resource-efficient production technologies increasing production [high levels of agricultural knowledge, science, and technology (high AKST)], particularly in Africa. Both scenarios suggest a global decrease in MSA for rangelands until 2050. The contribution of livestock grazing to MSA loss is, however, expected to diminish after 2030, in particular in Africa under the high AKST scenario. Policies fostering agricultural intensification can reduce the overall pressure on rangeland biodiversity, but additional measures, addressing factors such as climate change and infrastructural development, are necessary to totally halt biodiversity loss. PMID- 22308314 TI - Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia. AB - Antiangiogenic therapy has been thought to hold significant potential for the treatment of cancer. However, the efficacy of such treatments, especially in breast cancer patients, has been called into question, as recent clinical trials reveal only limited effectiveness of antiangiogenic agents in prolonging patient survival. New research using preclinical models further suggests that antiangiogenic agents actually increase invasive and metastatic properties of breast cancer cells. We demonstrate that by generating intratumoral hypoxia in human breast cancer xenografts, the antiangiogenic agents sunitinib and bevacizumab increase the population of cancer stem cells. In vitro studies revealed that hypoxia-driven stem/progenitor cell enrichment is primarily mediated by hypoxia-inducible factor 1alpha. We further show that the Akt/beta catenin cancer stem cell regulatory pathway is activated in breast cancer cells under hypoxic conditions in vitro and in sunitinib-treated mouse xenografts. These studies demonstrate that hypoxia-driven cancer stem cell stimulation limits the effectiveness of antiangiogenic agents, and suggest that to improve patient outcome, these agents might have to be combined with cancer stem cell-targeting drugs. PMID- 22308315 TI - Profile of David M. Karl. PMID- 22308316 TI - Subunit architecture of general transcription factor TFIIH. AB - Structures of complete 10-subunit yeast TFIIH and of a nested set of subcomplexes, containing 5, 6, and 7 subunits, have been determined by electron microscopy (EM) and 3D reconstruction. Consistency among all the structures establishes the location of the "minimal core" subunits (Ssl1, Tfb1, Tfb2, Tfb4, and Tfb5), and additional densities can be specifically attributed to Rad3, Ssl2, and the TFIIK trimer. These results can be further interpreted by placement of previous X-ray structures into the additional densities to give a preliminary picture of the RNA polymerase II preinitiation complex. In this picture, the key catalytic components of TFIIH, the Ssl2 ATPase/helicase and the Kin28 protein kinase are in proximity to their targets, downstream promoter DNA and the RNA polymerase C-terminal domain. PMID- 22308317 TI - Cholera toxin activates nonconventional adjuvant pathways that induce protective CD8 T-cell responses after epicutaneous vaccination. AB - The ability to induce humoral and cellular immunity via antigen delivery through the unbroken skin (epicutaneous immunization, EPI) has immediate relevance for vaccine development. However, it is unclear which adjuvants induce protective memory CD8 T-cell responses by this route, and the molecular and cellular requirements for priming through intact skin are not defined. We report that cholera toxin (CT) is superior to other adjuvants in its ability to prime memory CD8 T cells that control bacterial and viral challenges. Epicutaneous immunization with CT does not require engagement of classic toll-like receptor (TLR) and inflammasome pathways and, surprisingly, is independent of skin langerin-expressing cells (including Langerhans cells). However, CT adjuvanticity required type-I IFN sensitivity, participation of a Batf3-dependent dendritic cell (DC) population and engagement of CT with suitable gangliosides. Chemoenzymatic generation of CT-antigen fusion proteins led to efficient priming of the CD8 T-cell responses, paving the way for development of this immunization strategy as a therapeutic option. PMID- 22308318 TI - Thrombospondin-1 acts as a ligand for CD148 tyrosine phosphatase. AB - CD148 is a receptor-type protein tyrosine phosphatase that is expressed in several cell types, including vascular endothelial cells and duct epithelial cells. Growing evidence demonstrates a prominent role for CD148 in negative regulation of growth factor signals, suppressing cell proliferation and transformation. However, its extracellular ligand(s) remain unknown. To identify the ligand(s) of CD148, we introduced HA-tagged CD148 into cultured endothelial cells and then isolated its interacting extracellular protein(s) by biotin surface labeling and subsequent affinity purifications. The binding proteins were identified by mass spectrometry. Here we report that soluble thrombospondin-1 (TSP1) binds to the extracellular part of CD148 with high affinity and specificity, and its binding increases CD148 catalytic activity, leading to dephosphorylation of the substrate proteins. Consistent with these findings, introduction of CD148 conferred TSP1-mediated inhibition of cell growth to cells which lack CD148 and TSP1 inhibition of growth. Further, we demonstrate that TSP1 mediated inhibition of endothelial cell growth is antagonized by soluble CD148 ectodomain as well as by CD148 gene silencing. These findings provide evidence that CD148 functions as a receptor for TSP1 and mediates its inhibition of cell growth. PMID- 22308319 TI - A small world of weak ties provides optimal global integration of self-similar modules in functional brain networks. AB - The human brain is organized in functional modules. Such an organization presents a basic conundrum: Modules ought to be sufficiently independent to guarantee functional specialization and sufficiently connected to bind multiple processors for efficient information transfer. It is commonly accepted that small-world architecture of short paths and large local clustering may solve this problem. However, there is intrinsic tension between shortcuts generating small worlds and the persistence of modularity, a global property unrelated to local clustering. Here, we present a possible solution to this puzzle. We first show that a modified percolation theory can define a set of hierarchically organized modules made of strong links in functional brain networks. These modules are "large world" self-similar structures and, therefore, are far from being small-world. However, incorporating weaker ties to the network converts it into a small world preserving an underlying backbone of well-defined modules. Remarkably, weak ties are precisely organized as predicted by theory maximizing information transfer with minimal wiring cost. This trade-off architecture is reminiscent of the "strength of weak ties" crucial concept of social networks. Such a design suggests a natural solution to the paradox of efficient information flow in the highly modular structure of the brain. PMID- 22308320 TI - Src tyrosine kinase phosphorylation of nuclear receptor HNF4alpha correlates with isoform-specific loss of HNF4alpha in human colon cancer. AB - Src tyrosine kinase has long been implicated in colon cancer but much remains to be learned about its substrates. The nuclear receptor hepatocyte nuclear factor 4alpha (HNF4alpha) has just recently been implicated in colon cancer but its role is poorly defined. Here we show that c-Src phosphorylates human HNF4alpha on three tyrosines in an interdependent and isoform-specific fashion. The initial phosphorylation site is a Tyr residue (Y14) present in the N-terminal A/B domain of P1- but not P2-driven HNF4alpha. Phospho-Y14 interacts with the Src SH2 domain, leading to the phosphorylation of two additional tyrosines in the ligand binding domain (LBD) in P1-HNF4alpha. Phosphomimetic mutants in the LBD decrease P1-HNF4alpha protein stability, nuclear localization and transactivation function. Immunohistochemical analysis of approximately 450 human colon cancer specimens (Stage III) reveals that P1-HNF4alpha is either lost or localized in the cytoplasm in approximately 80% of tumors, and that staining for active Src correlates with those events in a subset of samples. Finally, three SNPs in the human HNF4alpha protein, two of which are in the HNF4alpha F domain that interacts with the Src SH3 domain, increase phosphorylation by Src and decrease HNF4alpha protein stability and function, suggesting that individuals with those variants may be more susceptible to Src-mediated effects. This newly identified interaction between Src kinase and HNF4alpha has important implications for colon and other cancers. PMID- 22308321 TI - Extensive X-linked adaptive evolution in central chimpanzees. AB - Surveying genome-wide coding variation within and among species gives unprecedented power to study the genetics of adaptation, in particular the proportion of amino acid substitutions fixed by positive selection. Additionally, contrasting the autosomes and the X chromosome holds information on the dominance of beneficial (adaptive) and deleterious mutations. Here we capture and sequence the complete exomes of 12 chimpanzees and present the largest set of protein coding polymorphism to date. We report extensive adaptive evolution specifically targeting the X chromosome of chimpanzees with as much as 30% of all amino acid replacements being adaptive. Adaptive evolution is barely detectable on the autosomes except for a few striking cases of recent selective sweeps associated with immunity gene clusters. We also find much stronger purifying selection than observed in humans, and in contrast to humans, we find that purifying selection is stronger on the X chromosome than on the autosomes in chimpanzees. We therefore conclude that most adaptive mutations are recessive. We also document dramatically reduced synonymous diversity in the chimpanzee X chromosome relative to autosomes and stronger purifying selection than for the human X chromosome. If similar processes were operating in the human-chimpanzee ancestor as in central chimpanzees today, our results therefore provide an explanation for the much discussed reduction in the human-chimpanzee divergence at the X chromosome. PMID- 22308322 TI - The El Nino-Southern Oscillation (ENSO)-pandemic influenza connection: coincident or causal? AB - We find that the four most recent human influenza pandemics (1918, 1957, 1968, and 2009), all of which were first identified in boreal spring or summer, were preceded by La Nina conditions in the equatorial Pacific. Changes in the phase of the El Nino-Southern Oscillation have been shown to alter the migration, stopover time, fitness, and interspecies mixing of migratory birds, and consequently, likely affect their mixing with domestic animals. We hypothesize that La Nina conditions bring divergent influenza subtypes together in some parts of the world and favor the reassortment of influenza through simultaneous multiple infection of individual hosts and the generation of novel pandemic strains. We propose approaches to test this hypothesis using influenza population genetics, virus prevalence in various host species, and avian migration patterns. PMID- 22308323 TI - Functional characteristics of developmental dyslexia in left-hemispheric posterior brain regions predate reading onset. AB - Individuals with developmental dyslexia (DD) show a disruption in posterior left hemispheric neural networks during phonological processing. Additionally, compensatory mechanisms in children and adults with DD have been located within frontal brain areas. However, it remains unclear when and how differences in posterior left-hemispheric networks manifest and whether compensatory mechanisms have already started to develop in the prereading brain. Here we investigate functional networks during phonological processing in 36 prereading children with a familial risk for DD (n = 18, average age = 66.50 mo) compared with age and IQ matched controls (n = 18; average age = 65.61 mo). Functional neuroimaging results reveal reduced activation in prereading children with a family-history of DD (FHD(+)), compared with those without (FHD(-)), in bilateral occipitotemporal and left temporoparietal brain regions. This finding corresponds to previously identified hypoactivations in left hemispheric posterior brain regions for school aged children and adults with a diagnosis of DD. Furthermore, left occipitotemporal and temporoparietal brain activity correlates positively with prereading skills in both groups. Our results suggest that differences in neural correlates of phonological processing in individuals with DD are not a result of reading failure, but are present before literacy acquisition starts. Additionally, no hyperactivation in frontal brain regions was observed, suggesting that compensatory mechanisms for reading failure are not yet present. Future longitudinal studies are needed to determine whether the identified differences may serve as neural premarkers for the early identification of children at risk for DD. PMID- 22308324 TI - Daily bursts of biogenic cyanogen bromide (BrCN) control biofilm formation around a marine benthic diatom. AB - The spatial organization of biofilms is strongly regulated by chemical cues released by settling organisms. However, the exact nature of these interactions and the repertoire of chemical cues and signals that micro-organisms produce and exude in response to the presence of competitors remain largely unexplored. Biofilms dominated by microalgae often show remarkable, yet unexplained fine scale patchy variation in species composition. Because this occurs even in absence of abiotic heterogeneity, antagonistic interactions might play a key role. Here we show that a marine benthic diatom produces chemical cues that cause chloroplast bleaching, a reduced photosynthetic efficiency, growth inhibition and massive cell death in naturally co-occurring competing microalgae. Using headspace solid phase microextraction (HS-SPME)-GC-MS, we demonstrate that this diatom exudes a diverse mixture of volatile iodinated and brominated metabolites including the natural product cyanogen bromide (BrCN), which exhibits pronounced allelopathic activity. Toxin production is light-dependent with a short BrCN burst after sunrise. BrCN acts as a short-term signal, leading to daily "cleaning" events around the algae. We show that allelopathic effects are H(2)O(2) dependent and link BrCN production to haloperoxidase activity. This strategy is a highly effective means of biofilm control and may provide an explanation for the poorly understood role of volatile halocarbons from marine algae, which contribute significantly to the atmospheric halocarbon budget. PMID- 22308325 TI - Highly localized sensitivity to climate forcing drives endemic cholera in a megacity. AB - The population dynamics of endemic cholera in urban environments--in particular interannual variation in the size and distribution of seasonal outbreaks--remain poorly understood and highly unpredictable. In part, this situation is due to the considerable demographic, socioeconomic, and environmental heterogeneity of large and growing urban centers. Despite this heterogeneity, the influence of climate variability on the population dynamics of infectious diseases is considered a large-scale, regional, phenomenon, and as such has been previously addressed for cholera only with temporal models that do not incorporate spatial structure. Here we show that a probabilistic spatial model can explain cholera dynamics in the megacity of Dhaka, Bangladesh, and afford a basis for cholera forecasts at lead times of 11 mo. Critically, we find that the action of climate variability (El Nino southern oscillation and flooding) is quite localized: There is a climate sensitive urban core that acts to propagate risk to the rest of the city. The modeling framework presented here should be applicable to cholera in other cities, as well as to other infectious diseases in urban settings and other biological systems with spatiotemporal interactions. PMID- 22308326 TI - Tight coevolution of proliferating cell nuclear antigen (PCNA)-partner interaction networks in fungi leads to interspecies network incompatibility. AB - The structure and connectivity of protein-protein interaction (PPI) networks are maintained throughout evolution by coordinated changes (coevolution) of network proteins. Despite extensive research, relatively little is known regarding the molecular basis and functional implications of the coevolution of PPI networks. Here, we used proliferating cell nuclear antigen, a hub protein that mediates DNA replication and repair in eukaryotes, as a model system to study the coevolution of PPI networks in fungi. Using a combined bioinformatics and experimental approach, we discovered that PCNA-partner interactions tightly coevolved in fungal species, leading to specific modes of recognition. We found that fungal proliferating cell nuclear antigen-partner interaction networks diverged into two distinct groups as a result of such coevolution and that hybrid networks of these groups are functionally noncompatible in Saccharomyces cerevisiae. Our results indicate that the coevolution of PPI networks can form functional barriers between fungal species, and thus can promote and fix speciation. PMID- 22308327 TI - Active transcription and essential role of RNA polymerase II at the centromere during mitosis. AB - Transcription of the centromeric regions has been reported to occur in G1 and S phase in different species. Here, we investigate whether transcription also occurs and plays a functional role at the mammalian centromere during mitosis. We show the presence of actively transcribing RNA polymerase II (RNAPII) and its associated transcription factors, coupled with the production of centromere satellite transcripts at the mitotic kinetochore. Specific inhibition of RNAPII activity during mitosis leads to a decrease in centromeric alpha-satellite transcription and a concomitant increase in anaphase-lagging cells, with the lagging chromosomes showing reduced centromere protein C binding. These findings demonstrate an essential role of RNAPII in the transcription of alpha-satellite DNA, binding of centromere protein C, and the proper functioning of the mitotic kinetochore. PMID- 22308328 TI - Trisomy of the G protein-coupled K+ channel gene, Kcnj6, affects reward mechanisms, cognitive functions, and synaptic plasticity in mice. AB - G protein-activated inwardly rectifying K+ channels (GIRK) generate slow inhibitory postsynaptic potentials in the brain via G(i/o) protein-coupled receptors. GIRK2, a GIRK subunit, is widely abundant in the brain and has been implicated in various functions and pathologies, such as learning and memory, reward, motor coordination, and Down syndrome. Down syndrome, the most prevalent cause of mental retardation, results from the presence of an extra maternal chromosome 21 (trisomy 21), which comprises the Kcnj6 gene (GIRK2). The present study examined the behaviors and cellular physiology properties in mice harboring a single trisomy of the Kcnj6 gene. Kcnj6 triploid mice exhibit deficits in hippocampal-dependent learning and memory, altered responses to rewards, hampered depotentiation, a form of excitatory synaptic plasticity, and have accentuated long-term synaptic depression. Collectively the findings suggest that triplication of Kcnj6 gene may play an active role in some of the abnormal neurological phenotypes found in Down syndrome. PMID- 22308329 TI - Mineralogical effects on the detectability of the postperovskite boundary. AB - The discovery of a phase transition in Mg-silicate perovskite (Pv) to postperovskite (pPv) at lowermost mantle pressure-temperature (P - T) conditions may provide an explanation for the discontinuous increase in shear wave velocity found in some regions at a depth range of 200 to 400 km above the core-mantle boundary, hereafter the D('') discontinuity. However, recent studies on binary and ternary systems showed that reasonable contents of Fe(2+) and Al for pyrolite increase the thickness (width of the mixed phase region) of the Pv - pPv boundary (400-600 km) to much larger than the D('') discontinuity (<= 70 km). These results challenge the assignment of the D('') discontinuity to the Pv - pPv boundary in pyrolite (homogenized mantle composition). Furthermore, the mineralogy and composition of rocks that can host a detectable Pv -> pPv boundary are still unknown. Here we report in situ measurements of the depths and thicknesses of the Pv -> pPv transition in multiphase systems (San Carlos olivine, pyrolitic, and midocean ridge basaltic compositions) at the P - T conditions of the lowermost mantle, searching for candidate rocks with a sharp Pv - pPv discontinuity. Whereas the pyrolitic mantle may not have a seismologically detectable Pv -> pPv transition due to the effect of Al, harzburgitic compositions have detectable transitions due to low Al content. In contrast, Al rich basaltic compositions may have a detectable Pv - pPv boundary due to their distinct mineralogy. Therefore, the observation of the D('') discontinuity may be related to the Pv -> pPv transition in the differentiated oceanic lithosphere materials transported to the lowermost mantle by subducting slabs. PMID- 22308330 TI - Oldest known dinosaurian nesting site and reproductive biology of the Early Jurassic sauropodomorph Massospondylus. AB - The extensive Early Jurassic continental strata of southern Africa have yielded an exceptional record of dinosaurs that includes scores of partial to complete skeletons of the sauropodomorph Massospondylus, ranging from embryos to large adults. In 1976 an incomplete egg clutch including in ovo embryos of this dinosaur, the oldest known example in the fossil record, was collected from a road-cut talus, but its exact provenance was uncertain. An excavation program at the site started in 2006 has yielded multiple in situ egg clutches, documenting the oldest known dinosaurian nesting site, predating other similar sites by more than 100 million years. The presence of numerous clutches of eggs, some of which contain embryonic remains, in at least four distinct horizons within a small area, provides the earliest known evidence of complex reproductive behavior including site fidelity and colonial nesting in a terrestrial vertebrate. Thus, fossil and sedimentological evidence from this nesting site provides empirical data on reproductive strategies in early dinosaurs. A temporally calibrated optimization of dinosaurian reproductive biology not only demonstrates the primary significance of the Massospondylus nesting site, but also provides additional insights into the initial stages of the evolutionary history of dinosaurs, including evidence that deposition of eggs in a tightly organized single layer in a nest evolved independently from brooding. PMID- 22308331 TI - Avian influenza virus hemagglutinins H2, H4, H8, and H14 support a highly pathogenic phenotype. AB - High-pathogenic avian influenza viruses (HPAIVs) evolve from low-pathogenic precursors specifying the HA serotypes H5 or H7 by acquisition of a polybasic HA cleavage site. As the reason for this serotype restriction has remained unclear, we aimed to distinguish between compatibility of a polybasic cleavage site with H5/H7 HA only and unique predisposition of these two serotypes for insertion mutations. To this end, we introduced a polybasic cleavage site into the HA of several low-pathogenic avian strains with serotypes H1, H2, H3, H4, H6, H8, H10, H11, H14, or H15, and rescued HA reassortants after cotransfection with the genes from either a low-pathogenic H9N2 or high-pathogenic H5N1 strain. Oculonasal inoculation with those reassortants resulted in varying pathogenicity in chicken. Recombinants containing the engineered H2, H4, H8, or H14 in the HPAIV background were lethal and exhibited i.v. pathogenicity indices of 2.79, 2.37, 2.85, and 2.61, respectively, equivalent to naturally occurring H5 or H7 HPAIV. Moreover, the H2, H4, and H8 reassortants were transmitted to some contact chickens. The H2 reassortant gained two mutations in the M2 proton channel gate region, which is affected in some HPAIVs of various origins. Taken together, in the presence of a polybasic HA cleavage site, non-H5/H7 HA can support a highly pathogenic phenotype in the appropriate viral background, indicating requirement for further adaptation. Therefore, the restriction of natural HPAIV to serotypes H5 and H7 is likely a result of their unique predisposition for acquisition of a polybasic HA cleavage site. PMID- 22308332 TI - Aggregation of alpha-synuclein is kinetically controlled by intramolecular diffusion. AB - We hypothesize that the first step of aggregation of disordered proteins, such as alpha-synuclein, is controlled by the rate of backbone reconfiguration. When reconfiguration is fast, bimolecular association is not stable, but as reconfiguration slows, association is more stable and subsequent aggregation is faster. To investigate this hypothesis, we have measured the rate of intramolecular diffusion in alpha-synuclein, a protein involved in Parkinson's disease, under solvent conditions that accelerate or decelerate aggregation. Using the method of tryptophan-cysteine (Trp-Cys) quenching, the rate of intramolecular contact is measured in four different loops along the chain length. This intrinsically disordered protein is highly diffusive at low temperature at neutral pH, when aggregation is slow, and compacts and diffuses more slowly at high temperature or low pH, when aggregation is rapid. Diffusion also slows with the disease mutation A30P. This work provides unique insights into the earliest steps of alpha-synuclein aggregation pathway and should provide the basis for the development of drugs that can prevent aggregation at the initial stage. PMID- 22308333 TI - Mechanics of bacteriophage maturation. AB - Capsid maturation with large-scale subunit reorganization occurs in virtually all viruses that use a motor to package nucleic acid into preformed particles. A variety of ensemble studies indicate that the particles gain greater stability during this process, however, it is unknown which material properties of the fragile procapsids change. Using Atomic Force Microscopy-based nano-indentation, we study the development of the mechanical properties during maturation of bacteriophage HK97, a lambda-like phage of which the maturation-induced morphological changes are well described. We show that mechanical stabilization and strengthening occurs in three independent ways: (i) an increase of the Young's modulus, (ii) a strong rise of the capsid's ultimate strength, and (iii) a growth of the resistance against material fatigue. The Young's modulus of immature and mature capsids, as determined from thin shell theory, fit with the values calculated using a new multiscale simulation approach. This multiscale calculation shows that the increase in Young's modulus isn't dependent on the crosslinking between capsomers. In contrast, the ultimate strength of the capsids does increase even when a limited number of cross-links are formed while full crosslinking appears to protect the shell against material fatigue. Compared to phage lambda, the covalent crosslinking at the icosahedral and quasi threefold axes of HK97 yields a mechanically more robust particle than the addition of the gpD protein during maturation of phage lambda. These results corroborate the expected increase in capsid stability and strength during maturation, however in an unexpected intricate way, underlining the complex structure of these self assembling nanocontainers. PMID- 22308334 TI - Education of a model student. AB - A dilemma faced by teachers, and increasingly by designers of educational software, is the trade-off between teaching new material and reviewing what has already been taught. Complicating matters, review is useful only if it is neither too soon nor too late. Moreover, different students need to review at different rates. We present a mathematical model that captures these issues in idealized form. The student's needs are modeled as constraints on the schedule according to which educational material and review are spaced over time. Our results include algorithms to construct schedules that adhere to various spacing constraints, and bounds on the rate at which new material can be introduced under these schedules. PMID- 22308335 TI - Histone density is maintained during transcription mediated by the chromatin remodeler RSC and histone chaperone NAP1 in vitro. AB - ATPases and histone chaperones facilitate RNA polymerase II (pol II) elongation on chromatin. In vivo, the coordinated action of these enzymes is necessary to permit pol II passage through a nucleosome while restoring histone density afterward. We have developed a biochemical system recapitulating this basic process. Transcription through a nucleosome in vitro requires the ATPase remodels structure of chromatin (RSC) and the histone chaperone nucleosome assembly protein 1 (NAP1). In the presence of NAP1, RSC generates a hexasome. Despite the propensity of RSC to evict histones, NAP1 reprograms the reaction such that the hexasome is retained on the template during multiple rounds of transcription. This work has implications toward understanding the mechanism of pol II elongation on chromatin. PMID- 22308336 TI - Evolution of functional specialization and division of labor. AB - Division of labor among functionally specialized modules occurs at all levels of biological organization in both animals and plants. Well-known examples include the evolution of specialized enzymes after gene duplication, the evolution of specialized cell types, limb diversification in arthropods, and the evolution of specialized colony members in many taxa of marine invertebrates and social insects. Here, we identify conditions favoring the evolution of division of labor by means of a general mathematical model. Our starting point is the assumption that modules contribute to two different biological tasks and that the potential of modules to contribute to these tasks is traded off. Our results are phrased in terms of properties of performance functions that map the phenotype of modules to measures of performance. We show that division of labor is favored by three factors: positional effects that predispose modules for one of the tasks, accelerating performance functions, and synergistic interactions between modules. If modules can be lost or damaged, selection for robustness can counteract selection for functional specialization. To illustrate our theory we apply it to the evolution of specialized enzymes coded by duplicated genes. PMID- 22308337 TI - Partitioning sexual selection into its mating success and fertilization success components. AB - Postcopulatory sexual selection due to sperm competition and/or cryptic female choice has been documented in a diversity of taxonomic groups and is considered a pivotal component of sexual selection. Despite this apparent importance, the relative contribution of postcopulatory fertilization success to overall sexual selection has not yet been measured in any species. Here, we used a laboratory adapted population of the promiscuous fruit fly Drosophila melanogaster to partition the variance in male reproductive success into mating success (a major component of precopulatory sexual selection) and fertilization success (a major component of postcopulatory sexual selection). We found that fertilization success contributed nearly as strongly as mating success to a male's net performance in sexual selection, but that most of this postcopulatory component was attributable to variation in male mating order (the tendency to be the last male to mate a female). After adjusting for mating order, only ~2% of the residual variation in male reproductive success was attributable to differential fertilization success. We found no correlation between male mating success and fertilization success in this system. Unlike natural populations of Drosophila, our laboratory population is adapted to a semelparous lifecycle, so our findings will be most applicable to other promiscuous species with strong sperm precedence and one short breeding period per year or lifetime. In these species, fertilization success may have as much influence on male reproductive success as mating success, but the timing of mating (mating order) may be the predominant factor contributing to variation in fertilization success. PMID- 22308338 TI - Light stimuli control neuronal migration by altering of insulin-like growth factor 1 (IGF-1) signaling. AB - The role of genetic inheritance in brain development has been well characterized, but little is known about the contributions of natural environmental stimuli, such as the effect of light-dark cycles, to brain development. In this study, we determined the role of light stimuli in neuronal cell migration to elucidate how environmental factors regulate brain development. We show that in early postnatal mouse cerebella, granule cell migration accelerates during light cycles and decelerates during dark cycles. Furthermore, cerebellar levels of insulin-like growth factor 1 (IGF-1) are high during light cycles and low during dark cycles. There are causal relationships between light-dark cycles, speed of granule cell migration, and cerebellar IGF-1 levels. First, changes in light-dark cycles result in corresponding changes in the fluctuations of both speed of granule cell migration and cerebellar IGF-1 levels. Second, in vitro studies indicate that exogenous IGF-1 accelerates the migration of isolated granule cells through the activation of IGF-1 receptors. Third, in vivo studies reveal that inhibiting the IGF-1 receptors decelerates granule cell migration during light cycles (high IGF 1 levels) but does not alter migration during dark cycles (low IGF-1 levels). In contrast, stimulating the IGF-1 receptors accelerates granule cell migration during dark cycles (low IGF-1 levels) but does not alter migration during light cycles (high IGF-1 levels). These results suggest that during early postnatal development light stimuli control granule cell migration by altering the activity of IGF-1 receptors through modification of cerebellar IGF-1 levels. PMID- 22308339 TI - Quantitative, directional measurement of electric field heterogeneity in the active site of ketosteroid isomerase. AB - Understanding the electrostatic forces and features within highly heterogeneous, anisotropic, and chemically complex enzyme active sites and their connection to biological catalysis remains a longstanding challenge, in part due to the paucity of incisive experimental probes of electrostatic properties within proteins. To quantitatively assess the landscape of electrostatic fields at discrete locations and orientations within an enzyme active site, we have incorporated site-specific thiocyanate vibrational probes into multiple positions within bacterial ketosteroid isomerase. A battery of X-ray crystallographic, vibrational Stark spectroscopy, and NMR studies revealed electrostatic field heterogeneity of 8 MV/cm between active site probe locations and widely differing sensitivities of discrete probes to common electrostatic perturbations from mutation, ligand binding, and pH changes. Electrostatic calculations based on active site ionization states assigned by literature precedent and computational pK(a) prediction were unable to quantitatively account for the observed vibrational band shifts. However, electrostatic models of the D40N mutant gave qualitative agreement with the observed vibrational effects when an unusual ionization of an active site tyrosine with a pK(a) near 7 was included. UV-absorbance and (13)C NMR experiments confirmed the presence of a tyrosinate in the active site, in agreement with electrostatic models. This work provides the most direct measure of the heterogeneous and anisotropic nature of the electrostatic environment within an enzyme active site, and these measurements provide incisive benchmarks for further developing accurate computational models and a foundation for future tests of electrostatics in enzymatic catalysis. PMID- 22308340 TI - Regional drought-induced reduction in the biomass carbon sink of Canada's boreal forests. AB - The boreal forests, identified as a critical "tipping element" of the Earth's climate system, play a critical role in the global carbon budget. Recent findings have suggested that terrestrial carbon sinks in northern high-latitude regions are weakening, but there has been little observational evidence to support the idea of a reduction of carbon sinks in northern terrestrial ecosystems. Here, we estimated changes in the biomass carbon sink of natural stands throughout Canada's boreal forests using data from long-term forest permanent sampling plots. We found that in recent decades, the rate of biomass change decreased significantly in western Canada (Alberta, Saskatchewan, and Manitoba), but there was no significant trend for eastern Canada (Ontario and Quebec). Our results revealed that recent climate change, and especially drought-induced water stress, is the dominant cause of the observed reduction in the biomass carbon sink, suggesting that western Canada's boreal forests may become net carbon sources if the climate change-induced droughts continue to intensify. PMID- 22308341 TI - Diabetes promotes an inflammatory macrophage phenotype and atherosclerosis through acyl-CoA synthetase 1. AB - The mechanisms that promote an inflammatory environment and accelerated atherosclerosis in diabetes are poorly understood. We show that macrophages isolated from two different mouse models of type 1 diabetes exhibit an inflammatory phenotype. This inflammatory phenotype associates with increased expression of long-chain acyl-CoA synthetase 1 (ACSL1), an enzyme that catalyzes the thioesterification of fatty acids. Monocytes from humans and mice with type 1 diabetes also exhibit increased ACSL1. Furthermore, myeloid-selective deletion of ACSL1 protects monocytes and macrophages from the inflammatory effects of diabetes. Strikingly, myeloid-selective deletion of ACSL1 also prevents accelerated atherosclerosis in diabetic mice without affecting lesions in nondiabetic mice. Our observations indicate that ACSL1 plays a critical role by promoting the inflammatory phenotype of macrophages associated with type 1 diabetes; they also raise the possibilities that diabetic atherosclerosis has an etiology that is, at least in part, distinct from the etiology of nondiabetic vascular disease and that this difference is because of increased monocyte and macrophage ACSL1 expression. PMID- 22308342 TI - Mitochondrial genomes from modern horses reveal the major haplogroups that underwent domestication. AB - Archaeological and genetic evidence concerning the time and mode of wild horse (Equus ferus) domestication is still debated. High levels of genetic diversity in horse mtDNA have been detected when analyzing the control region; recurrent mutations, however, tend to blur the structure of the phylogenetic tree. Here, we brought the horse mtDNA phylogeny to the highest level of molecular resolution by analyzing 83 mitochondrial genomes from modern horses across Asia, Europe, the Middle East, and the Americas. Our data reveal 18 major haplogroups (A-R) with radiation times that are mostly confined to the Neolithic and later periods and place the root of the phylogeny corresponding to the Ancestral Mare Mitogenome at ~130-160 thousand years ago. All haplogroups were detected in modern horses from Asia, but F was only found in E. przewalskii--the only remaining wild horse. Therefore, a wide range of matrilineal lineages from the extinct E. ferus underwent domestication in the Eurasian steppes during the Eneolithic period and were transmitted to modern E. caballus breeds. Importantly, now that the major horse haplogroups have been defined, each with diagnostic mutational motifs (in both the coding and control regions), these haplotypes could be easily used to (i) classify well-preserved ancient remains, (ii) (re)assess the haplogroup variation of modern breeds, including Thoroughbreds, and (iii) evaluate the possible role of mtDNA backgrounds in racehorse performance. PMID- 22308343 TI - Modulation of value representation by social context in the primate orbitofrontal cortex. AB - Primates depend for their survival on their ability to understand their social environment, and their behavior is often shaped by social circumstances. We report that the orbitofrontal cortex, a brain region involved in motivation and reward, is tuned to social information. Macaque monkeys worked to collect rewards for themselves and two monkey partners. Behaviorally, monkeys discriminated between cues signaling large and small [corrected] rewards, and between cues signaling rewards to self only and reward to both self and another monkey, with a preference for the former over the latter in both instances. Single neurons recorded during this task encoded the meaning of visual cues that predicted the magnitude of future rewards, as well as the motivational value of rewards obtained in a social context. Furthermore, neuronal activity was found to track momentary social preferences and partner's identity and social rank. The orbitofrontal cortex thus contains key neuronal mechanisms for the evaluation of social information. PMID- 22308344 TI - Regulation of prelamin A but not lamin C by miR-9, a brain-specific microRNA. AB - Lamins A and C, alternatively spliced products of the LMNA gene, are key components of the nuclear lamina. The two isoforms are found in similar amounts in most tissues, but we observed an unexpected pattern of expression in the brain. Western blot and immunohistochemistry studies showed that lamin C is abundant in the mouse brain, whereas lamin A and its precursor prelamin A are restricted to endothelial cells and meningeal cells and are absent in neurons and glia. Prelamin A transcript levels were low in the brain, but this finding could not be explained by alternative splicing. In lamin A-only knockin mice, where alternative splicing is absent and all the output of the gene is channeled into prelamin A transcripts, large amounts of lamin A were found in peripheral tissues, but there was very little lamin A in the brain. Also, in knockin mice expressing exclusively progerin (a toxic form of prelamin A found in Hutchinson Gilford progeria syndrome), the levels of progerin in the brain were extremely low. Further studies showed that prelamin A expression, but not lamin C expression, is down-regulated by a brain-specific microRNA, miR-9. Expression of miR-9 in cultured cells reduced lamin A expression, and this effect was abolished when the miR-9-binding site in the prelamin A 3' UTR was mutated. The down regulation of prelamin A expression in the brain could explain why mouse models of Hutchinson-Gilford progeria syndrome are free of central nervous system pathology. PMID- 22308345 TI - Dominant folding pathways of a WW domain. AB - We investigate the folding mechanism of the WW domain Fip35 using a realistic atomistic force field by applying the Dominant Reaction Pathways approach. We find evidence for the existence of two folding pathways, which differ by the order of formation of the two hairpins. This result is consistent with the analysis of the experimental data on the folding kinetics of WW domains and with the results obtained from large-scale molecular dynamics simulations of this system. Free-energy calculations performed in two coarse-grained models support the robustness of our results and suggest that the qualitative structure of the dominant paths are mostly shaped by the native interactions. Computing a folding trajectory in atomistic detail only required about one hour on 48 Central Processing Units. The gain in computational efficiency opens the door to a systematic investigation of the folding pathways of a large number of globular proteins. PMID- 22308346 TI - pH-controlled delivery of luminescent europium coated nanoparticles into platelets. AB - Water soluble, luminescent gold nanoparticles are delivered into human platelets via a rapid, pH-controlled mechanism using a pH low insertion peptide, pHLIP. The approach introduces cocoating of gold nanoparticles with a europium luminescent complex, EuL and the pHLIP peptide to give pHLIP*EuL*Au. The 13-nm diameter gold nanoparticles act as a scaffold for the attachment of both the luminescent probe and the peptide to target delivery. Their size allows delivery of approximately 640 lanthanide probes per nanoparticle to be internalized in human platelets, which are not susceptible to transfection or microinjection. The internalization of pHLIP*EuL*Au in platelets, which takes just minutes, was studied with a variety of imaging modalities including luminescence, confocal reflection, and transmission electron microscopy. The results show that pHLIP*EuL*Au only enters the platelets in low pH conditions, pH 6.5, mediated by the pHLIP translocation across the membrane, and not at pH 7.4. Luminescence microscopy images of the treated platelets show clearly the red luminescence signal from the europium probe and confocal reflection microscopy confirms the presence of the gold particles. Furthermore, transmission electron microscopy gives a detailed insight of the internalization and spatial localization of the gold nanoparticles in the platelets. Thus, we demonstrate the potential of the design to translocate multimodal nanoparticle probes into cells in a pH dependent manner. PMID- 22308347 TI - Withania somnifera reverses Alzheimer's disease pathology by enhancing low density lipoprotein receptor-related protein in liver. AB - A 30-d course of oral administration of a semipurified extract of the root of Withania somnifera consisting predominantly of withanolides and withanosides reversed behavioral deficits, plaque pathology, accumulation of beta-amyloid peptides (Abeta) and oligomers in the brains of middle-aged and old APP/PS1 Alzheimer's disease transgenic mice. It was similarly effective in reversing behavioral deficits and plaque load in APPSwInd mice (line J20). The temporal sequence involved an increase in plasma Abeta and a decrease in brain Abeta monomer after 7 d, indicating increased transport of Abeta from the brain to the periphery. Enhanced expression of low-density lipoprotein receptor-related protein (LRP) in brain microvessels and the Abeta-degrading protease neprilysin (NEP) occurred 14-21 d after a substantial decrease in brain Abeta levels. However, significant increase in liver LRP and NEP occurred much earlier, at 7 d, and were accompanied by a rise in plasma sLRP, a peripheral sink for brain Abeta. In WT mice, the extract induced liver, but not brain, LRP and NEP and decreased plasma and brain Abeta, indicating that increase in liver LRP and sLRP occurring independent of Abeta concentration could result in clearance of Abeta. Selective down-regulation of liver LRP, but not NEP, abrogated the therapeutic effects of the extract. The remarkable therapeutic effect of W. somnifera mediated through up-regulation of liver LRP indicates that targeting the periphery offers a unique mechanism for Abeta clearance and reverses the behavioral deficits and pathology seen in Alzheimer's disease models. PMID- 22308348 TI - Use of red ochre by early Neandertals. AB - The use of manganese and iron oxides by late Neandertals is well documented in Europe, especially for the period 60-40 kya. Such finds often have been interpreted as pigments even though their exact function is largely unknown. Here we report significantly older iron oxide finds that constitute the earliest documented use of red ochre by Neandertals. These finds were small concentrates of red material retrieved during excavations at Maastricht-Belvedere, The Netherlands. The excavations exposed a series of well-preserved flint artifact (and occasionally bone) scatters, formed in a river valley setting during a late Middle Pleistocene full interglacial period. Samples of the reddish material were submitted to various forms of analyses to study their physical properties. All analyses identified the red material as hematite. This is a nonlocal material that was imported to the site, possibly over dozens of kilometers. Identification of the Maastricht-Belvedere finds as hematite pushes the use of red ochre by (early) Neandertals back in time significantly, to minimally 200-250 kya (i.e., to the same time range as the early ochre use in the African record). PMID- 22308349 TI - Exclusive recognition of sarcosine in water and urine by a cavitand functionalized silicon surface. AB - A supramolecular approach for the specific detection of sarcosine, recently linked to the occurrence of aggressive prostate cancer forms, has been developed. A hybrid active surface was prepared by the covalent anchoring on Si substrates of a tetraphosphonate cavitand as supramolecular receptor and it was proven able to recognize sarcosine from its nonmethylated precursor, glycine, in water and urine. The entire complexation process has been investigated in the solid state, in solution, and at the solid-liquid interface to determine and weight all the factors responsible of the observed specificity. The final outcome is a Si-based active surface capable of binding exclusively sarcosine. The complete selectivity of the cavitand-decorated surface under these stringent conditions represents a critical step forward in the use of these materials for the specific detection of sarcosine and related metabolites in biological fluids. PMID- 22308350 TI - Probing chelation motifs in HIV integrase inhibitors. AB - A series of HIV integrase (HIV-1 IN) inhibitors were synthesized to evaluate the role of the metal-binding group (MBG) in this class of metalloenzyme inhibitors. A total of 21 different raltegravir-chelator derivative (RCD) compounds were prepared that differed only in the nature of the MBG. These IN strand-transfer inhibitors (INSTIs) were evaluated in vitro in cell-free enzyme activity assays, and the in vitro results were further validated in cell culture experiments. All of the active compounds showed selective inhibition of the strand-transfer reaction over 3'-processing, suggesting a common mode of action with raltegravir. The results of the in vitro activity suggest that the nature of the MBG donor atoms, the overall MBG structure, and the specific arrangement of the MBG donor atom triad are essential for obtaining maximal HIV-1 IN inhibition. At least two compounds (RCD-4, RCD-5) containing a hydroxypyrone MBG were found to display superior strand-transfer inhibition when compared to an abbreviated analogue of raltegravir (RCD-1). By isolating and examining the role of the MBG in a series of INSTIs, we have identified a scaffold (hydroxypyrones) that may provide access to a unique class of HIV-1 IN inhibitors, and may help overcome rising raltegravir resistance. PMID- 22308351 TI - Foraging alters resilience/vulnerability to sleep disruption and starvation in Drosophila. AB - Recent human studies suggest that genetic polymorphisms allow an individual to maintain optimal cognitive functioning during sleep deprivation. If such polymorphisms were not associated with additional costs, selective pressures would allow these alleles to spread through the population such that an evolutionary alternative to sleep would emerge. To determine whether there are indeed costs associated with resiliency to sleep loss, we challenged natural allelic variants of the foraging gene (for) with either sleep deprivation or starvation. Flies with high levels of Protein Kinase G (PKG) (for(R)) do not display deficits in short-term memory following 12 h of sleep deprivation. However, short-term memory is significantly disrupted when for(R) flies are starved overnight. In contrast, flies with low levels of PKG (for(s), for(s2)) show substantial deficits in short-term memory following sleep deprivation but retain their ability to learn after 12 h of starvation. We found that for(R) phenotypes could be largely recapitulated in for(s) flies by selectively increasing the level of PKG in the alpha/beta lobes of the mushroom bodies, a structure known to regulate both sleep and memory. Together, these data indicate that whereas the expression of for may appear to provide resilience in one environmental context, it may confer an unexpected vulnerability in other situations. Understanding how these tradeoffs confer resilience or vulnerability to specific environmental challenges may provide additional clues as to why an evolutionary alternative to sleep has not emerged. PMID- 22308352 TI - Pulmonary infection by Yersinia pestis rapidly establishes a permissive environment for microbial proliferation. AB - Disease progression of primary pneumonic plague is biphasic, consisting of a preinflammatory and a proinflammatory phase. During the long preinflammatory phase, bacteria replicate to high levels, seemingly uninhibited by normal pulmonary defenses. In a coinfection model of pneumonic plague, it appears that Yersinia pestis quickly creates a localized, dominant anti-inflammatory state that allows for the survival and rapid growth of both itself and normally avirulent organisms. Yersinia pseudotuberculosis, the relatively recent progenitor of Y. pestis, shows no similar trans-complementation effect, which is unprecedented among other respiratory pathogens. We demonstrate that the effectors secreted by the Ysc type III secretion system are necessary but not sufficient to mediate this apparent immunosuppression. Even an unbiased negative selection screen using a vast pool of Y. pestis mutants revealed no selection against any known virulence genes, demonstrating the transformation of the lung from a highly restrictive to a generally permissive environment during the preinflammatory phase of pneumonic plague. PMID- 22308353 TI - Target-of-rapamycin complex 1 (Torc1) signaling modulates cilia size and function through protein synthesis regulation. AB - The cilium serves as a cellular antenna by coordinating upstream environmental cues with numerous downstream signaling processes that are indispensable for the function of the cell. This role is supported by the revelation that defects of the cilium underlie an emerging class of human disorders, termed "ciliopathies." Although mounting interest in the cilium has demonstrated the essential role that the organelle plays in vertebrate development, homeostasis, and disease pathogenesis, the mechanisms regulating cilia morphology and function remain unclear. Here, we show that the target-of-rapamycin (TOR) growth pathway modulates cilia size and function during zebrafish development. Knockdown of tuberous sclerosis complex 1a (tsc1a), which encodes an upstream inhibitor of TOR complex 1 (Torc1), increases cilia length. In contrast, treatment of embryos with rapamycin, an inhibitor of Torc1, shortens cilia length. Overexpression of ribosomal protein S6 kinase 1 (S6k1), which encodes a downstream substrate of Torc1, lengthens cilia. Furthermore, we provide evidence that TOR-mediated cilia assembly is evolutionarily conserved and that protein synthesis is essential for this regulation. Finally, we demonstrate that TOR signaling and cilia length are pivotal for a variety of downstream ciliary functions, such as cilia motility, fluid flow generation, and the establishment of left-right body asymmetry. Our findings reveal a unique role for the TOR pathway in regulating cilia size through protein synthesis and suggest that appropriate and defined lengths are necessary for proper function of the cilium. PMID- 22308354 TI - Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver function. AB - A critical regulator of autophagy is the Class III PI3K Vps34 (also called PIK3C3). Although Vps34 is known to play an essential role in autophagy in yeast, its role in mammals remains elusive. To elucidate the physiological function of Vps34 and to determine its precise role in autophagy, we have generated Vps34(f/f) mice, in which expression of Cre recombinase results in a deletion of exon 4 of Vps34 and a frame shift causing a deletion of 755 of the 887 amino acids of Vps34. Acute ablation of Vps34 in MEFs upon adenoviral Cre infection results in a diminishment of localized generation of phosphatidylinositol 3 phosphate and blockade of both endocytic and autophagic degradation. Starvation induced autophagosome formation is blocked in both Vps34-null MEFs and liver. Liver-specific Albumin-Cre;Vps34(f/f) mice developed hepatomegaly and hepatic steatosis, and impaired protein turnover. Ablation of Vps34 in the heart of muscle creatine kinase-Cre;Vps34(f/f) mice led to cardiomegaly and decreased contractility. In addition, while amino acid-stimulated mTOR activation was suppressed in the absence of Vps34, the steady-state level of mTOR signaling was not affected in Vps34-null MEFs, liver, or cardiomyocytes. Taken together, our results indicate that Vps34 plays an essential role in regulating functional autophagy and is indispensable for normal liver and heart function. PMID- 22308355 TI - Quantitative modeling of the terminal differentiation of B cells and mechanisms of lymphomagenesis. AB - Mature B-cell exit from germinal centers is controlled by a transcriptional regulatory module that integrates antigen and T-cell signals and, ultimately, leads to terminal differentiation into memory B cells or plasma cells. Despite a compact structure, the module dynamics are highly complex because of the presence of several feedback loops and self-regulatory interactions, and understanding its dysregulation, frequently associated with lymphomagenesis, requires robust dynamical modeling techniques. We present a quantitative kinetic model of three key gene regulators, BCL6, IRF4, and BLIMP, and use gene expression profile data from mature human B cells to determine appropriate model parameters. The model predicts the existence of two different hysteresis cycles that direct B cells through an irreversible transition toward a differentiated cellular state. By synthetically perturbing the interactions in this network, we can elucidate known mechanisms of lymphomagenesis and suggest candidate tumorigenic alterations, indicating that the model is a valuable quantitative tool to simulate B-cell exit from the germinal center under a variety of physiological and pathological conditions. PMID- 22308356 TI - Optimizing ring assembly reveals the strength of weak interactions. AB - Most cellular processes rely on large multiprotein complexes that must assemble into a well-defined quaternary structure in order to function. A number of prominent examples, including the 20S core particle of the proteasome and the AAA+ family of ATPases, contain ring-like structures. Developing an understanding of the complex assembly pathways employed by ring-like structures requires a characterization of the problems these pathways have had to overcome as they evolved. In this work, we use computational models to uncover one such problem: a deadlocked plateau in the assembly dynamics. When the molecular interactions between subunits are too strong, this plateau leads to significant delays in assembly and a reduction in steady-state yield. Conversely, if the interactions are too weak, assembly delays are caused by the instability of crucial intermediates. Intermediate affinities thus maximize the efficiency of assembly for homomeric ring-like structures. In the case of heteromeric rings, we find that rings including at least one weak interaction can assemble efficiently and robustly. Estimation of affinities from solved structures of ring-like complexes indicates that heteromeric rings tend to contain a weak interaction, confirming our prediction. In addition to providing an evolutionary rationale for structural features of rings, our work forms the basis for understanding the complex assembly pathways of stacked rings like the proteasome and suggests principles that would aid in the design of synthetic ring-like structures that self-assemble efficiently. PMID- 22308357 TI - Toll-like receptor 3 signaling converts tumor-supporting myeloid cells to tumoricidal effectors. AB - Smoldering inflammation often increases the risk of progression for malignant tumors and simultaneously matures myeloid dendritic cells (mDCs) for cell mediated immunity. PolyI:C, a dsRNA analog, is reported to induce inflammation and potent antitumor immune responses via the Toll-like receptor 3/Toll-IL-1 receptor domain-containing adaptor molecule 1 (TICAM-1) and melanoma differentiation-associated protein 5/IFN-beta promoter stimulator 1 (IPS-1) pathways in mDCs to drive activation of natural killer cells and cytotoxic T lymphocytes. Here, we found that i.p. or s.c. injection of polyI:C to Lewis lung carcinoma tumor-implant mice resulted in tumor regression by converting tumor supporting macrophages (Mfs) to tumor suppressors. F4/80(+)/Gr1(-) Mfs infiltrating the tumor respond to polyI:C to rapidly produce inflammatory cytokines and thereafter accelerate M1 polarization. TNF-alpha was increased within 1 h in both tumor and serum upon polyI:C injection into tumor-bearing mice, followed by tumor hemorrhagic necrosis and growth suppression. These tumor responses were abolished in TNF-alpha(-/-) mice. Furthermore, F4/80(+) Mfs in tumors extracted from polyI:C-injected mice sustained Lewis lung carcinoma cytotoxic activity, and this activity was partly abrogated by anti-TNF-alpha Ab. Genes for supporting M1 polarization were subsequently up-regulated in the tumor infiltrating Mfs. These responses were completely abrogated in TICAM-1(-/-) mice, and unaffected in myeloid differentiation factor 88(-/-) and IPS-1(-/-) mice. Thus, the TICAM-1 pathway is not only important to mature mDCs for cross-priming and natural killer cell activation in the induction of tumor immunity, but also critically engaged in tumor suppression by converting tumor-supporting Mfs to those with tumoricidal properties. PMID- 22308359 TI - Insights into cis-autoproteolysis reveal a reactive state formed through conformational rearrangement. AB - ThnT is a pantetheine hydrolase from the DmpA/OAT superfamily involved in the biosynthesis of the beta-lactam antibiotic thienamycin. We performed a structural and mechanistic investigation into the cis-autoproteolytic activation of ThnT, a process that has not previously been subject to analysis within this superfamily of enzymes. Removal of the gamma-methyl of the threonine nucleophile resulted in a rate deceleration that we attribute to a reduction in the population of the reactive rotamer. This phenomenon is broadly applicable and constitutes a rationale for the evolutionary selection of threonine nucleophiles in autoproteolytic systems. Conservative substitution of the nucleophile (T282C) allowed determination of a 1.6-A proenzyme ThnT crystal structure, which revealed a level of structural flexibility not previously observed within an autoprocessing active site. We assigned the major conformer as a nonreactive state that is unable to populate a reactive rotamer. Our analysis shows the system is activated by a structural rearrangement that places the scissile amide into an oxyanion hole and forces the nucleophilic residue into a forbidden region of Ramachandran space. We propose that conformational strain may drive autoprocessing through the destabilization of nonproductive states. Comparison of our data with previous reports uncovered evidence that many inactivated structures display nonreactive conformations. For penicillin and cephalosporin acylases, this discrepancy between structure and function may be resolved by invoking the presence of a hidden conformational state, similar to that reported here for ThnT. PMID- 22308358 TI - Phoneme and word recognition in the auditory ventral stream. AB - Spoken word recognition requires complex, invariant representations. Using a meta analytic approach incorporating more than 100 functional imaging experiments, we show that preference for complex sounds emerges in the human auditory ventral stream in a hierarchical fashion, consistent with nonhuman primate electrophysiology. Examining speech sounds, we show that activation associated with the processing of short-timescale patterns (i.e., phonemes) is consistently localized to left mid-superior temporal gyrus (STG), whereas activation associated with the integration of phonemes into temporally complex patterns (i.e., words) is consistently localized to left anterior STG. Further, we show left mid- to anterior STG is reliably implicated in the invariant representation of phonetic forms and that this area also responds preferentially to phonetic sounds, above artificial control sounds or environmental sounds. Together, this shows increasing encoding specificity and invariance along the auditory ventral stream for temporally complex speech sounds. PMID- 22308360 TI - Near-infrared fluorescent sensor for in vivo copper imaging in a murine Wilson disease model. AB - Copper is an essential metal nutrient that is tightly regulated in the body because loss of its homeostasis is connected to severe diseases such as Menkes and Wilson diseases, Alzheimer's disease, prion disorders, and amyotrophic lateral sclerosis. The complex relationships between copper status and various stages of health and disease remain challenging to elucidate, in part due to a lack of methods for monitoring dynamic changes in copper pools in whole living organisms. Here we present the synthesis, spectroscopy, and in vivo imaging applications of Coppersensor 790, a first-generation fluorescent sensor for visualizing labile copper pools in living animals. Coppersensor 790 combines a near-infrared emitting cyanine dye with a sulfur-rich receptor to provide a selective and sensitive turn-on response to copper. This probe is capable of monitoring fluctuations in exchangeable copper stores in living cells and mice under basal conditions, as well as in situations of copper overload or deficiency. Moreover, we demonstrate the utility of this unique chemical tool to detect aberrant increases in labile copper levels in a murine model of Wilson disease, a genetic disorder that is characterized by accumulation of excess copper. The ability to monitor real-time copper fluxes in living animals offers potentially rich opportunities to examine copper physiology in health and disease. PMID- 22308361 TI - Origins of tumor-associated macrophages and neutrophils. AB - Tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) can control cancer growth and exist in almost all solid neoplasms. The cells are known to descend from immature monocytic and granulocytic cells, respectively, which are produced in the bone marrow. However, the spleen is also a recently identified reservoir of monocytes, which can play a significant role in the inflammatory response that follows acute injury. Here, we evaluated the role of the splenic reservoir in a genetic mouse model of lung adenocarcinoma driven by activation of oncogenic Kras and inactivation of p53. We found that high numbers of TAM and TAN precursors physically relocated from the spleen to the tumor stroma, and that recruitment of tumor-promoting spleen-derived TAMs required signaling of the chemokine receptor CCR2. Also, removal of the spleen, either before or after tumor initiation, reduced TAM and TAN responses significantly and delayed tumor growth. The mechanism by which the spleen was able to maintain its reservoir capacity throughout tumor progression involved, in part, local accumulation in the splenic red pulp of typically rare extramedullary hematopoietic stem and progenitor cells, notably granulocyte and macrophage progenitors, which produced CD11b(+) Ly-6C(hi) monocytic and CD11b(+) Ly-6G(hi) granulocytic cells locally. Splenic granulocyte and macrophage progenitors and their descendants were likewise identified in clinical specimens. The present study sheds light on the origins of TAMs and TANs, and positions the spleen as an important extramedullary site, which can continuously supply growing tumors with these cells. PMID- 22308362 TI - Host-targeting protein 1 (SpHtp1) from the oomycete Saprolegnia parasitica translocates specifically into fish cells in a tyrosine-O-sulphate-dependent manner. AB - The eukaryotic oomycetes, or water molds, contain several species that are devastating pathogens of plants and animals. During infection, oomycetes translocate effector proteins into host cells, where they interfere with host defense responses. For several oomycete effectors (i.e., the RxLR-effectors) it has been shown that their N-terminal polypeptides are important for the delivery into the host. Here we demonstrate that the putative RxLR-like effector, host targeting protein 1 (SpHtp1), from the fish pathogen Saprolegnia parasitica translocates specifically inside host cells. We further demonstrate that cell surface binding and uptake of this effector protein is mediated by an interaction with tyrosine-O-sulfate-modified cell-surface molecules and not via phospholipids, as has been reported for RxLR-effectors from plant pathogenic oomycetes. These results reveal an effector translocation route based on tyrosine O-sulfate binding, which could be highly relevant for a wide range of host microbe interactions. PMID- 22308363 TI - Adipose tissue-derived stem cell-seeded small intestinal submucosa for tunica albuginea grafting and reconstruction. AB - Porcine small intestinal submucosa (SIS) has been widely used in tunica albuginea (TA) reconstructive surgery. Adipose tissue-derived stem cells (ADSCs) can repair damaged tissue, augment cellular differentiation, and stimulate release of multiple growth factors. The aim of this rat study was to assess the feasibility of seeding ADSCs onto SIS grafts for TA reconstruction. Here, we demonstrate that seeding syngeneic ADSCs onto SIS grafts (SIS-ADSC) resulted in significant cavernosal tissue preservation and maintained erectile responses, similar to controls, in a rat model of bilateral incision of TA, compared with sham-operated animals and rats grafted with SIS graft (SIS) alone. In addition to increased TGF beta1 and FGF-2 expression levels, cross-sectional studies of the rat penis with SIS and SIS-ADSC revealed mild to moderate fibrosis and an increase of 30% and 40% in mean diameter in flaccid and erectile states, respectively. SIS grafting induced transcriptional up-regulation of iNOS and down-regulation of endothelial NOS, neuronal NOS, and VEGF, an effect that was restored by seeding ADCSs on the SIS graft. Taken together, these data show that rats undergoing TA incision with autologous SIS-ADSC grafts maintained better erectile function compared with animals grafted with SIS alone. This study suggests that SIS-ADSC grafting can be successfully used for TA reconstruction procedures and can restore erectile function. PMID- 22308364 TI - Reversal of tumoral immune resistance by inhibition of tryptophan 2,3 dioxygenase. AB - Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO1) is an important mechanism of peripheral immune tolerance contributing to tumoral immune resistance, and IDO1 inhibition is an active area of drug development. Tryptophan 2,3-dioxygenase (TDO) is an unrelated hepatic enzyme that also degrades tryptophan along the kynurenine pathway. Here, we show that enzymatically active TDO is expressed in a significant proportion of human tumors. In a preclinical model, TDO expression by tumors prevented their rejection by immunized mice. We developed a TDO inhibitor, which, upon systemic treatment, restored the ability of mice to reject TDO-expressing tumors. Our results describe a mechanism of tumoral immune resistance based on TDO expression and establish proof-of-concept for the use of TDO inhibitors in cancer therapy. PMID- 22308365 TI - On achieving high accuracy and reliability in the calculation of relative protein ligand binding affinities. AB - We apply a free energy perturbation simulation method, free energy perturbation/replica exchange with solute tempering, to two modifications of protein-ligand complexes that lead to significant conformational changes, the first in the protein and the second in the ligand. The approach is shown to facilitate sampling in these challenging cases where high free energy barriers separate the initial and final conformations and leads to superior convergence of the free energy as demonstrated both by consistency of the results (independence from the starting conformation) and agreement with experimental binding affinity data. The second case, consisting of two neutral thrombin ligands that are taken from a recent medicinal chemistry program for this interesting pharmaceutical target, is of particular significance in that it demonstrates that good results can be obtained for large, complex ligands, as opposed to relatively simple model systems. To achieve quantitative agreement with experiment in the thrombin case, a next generation force field, Optimized Potentials for Liquid Simulations 2.0, is required, which provides superior charges and torsional parameters as compared to earlier alternatives. PMID- 22308366 TI - Self-assembly of functional, amphipathic amyloid monolayers by the fungal hydrophobin EAS. AB - The hydrophobin EAS from the fungus Neurospora crassa forms functional amyloid fibrils called rodlets that facilitate spore formation and dispersal. Self assembly of EAS into fibrillar rodlets occurs spontaneously at hydrophobic:hydrophilic interfaces and the rodlets further associate laterally to form amphipathic monolayers. We have used site-directed mutagenesis and peptide experiments to identify the region of EAS that drives intermolecular association and formation of the cross-beta rodlet structure. Transplanting this region into a nonamyloidogenic hydrophobin enables it to form rodlets. We have also determined the structure and dynamics of an EAS variant with reduced rodlet forming ability. Taken together, these data allow us to pinpoint the conformational changes that take place when hydrophobins self-assemble at an interface and to propose a model for the amphipathic EAS rodlet structure. PMID- 22308367 TI - Horizontal transfer of chloroplast genomes between plant species. AB - The genomes of DNA-containing cell organelles (mitochondria, chloroplasts) can be laterally transmitted between organisms, a process known as organelle capture. Organelle capture often occurs in the absence of detectable nuclear introgression, and the capture mechanism is unknown. Here, we have considered horizontal genome transfer across natural grafts as a mechanism underlying chloroplast capture in plants. By grafting sexually incompatible species, we show that complete chloroplast genomes can travel across the graft junction from one species into another. We demonstrate that, consistent with reported phylogenetic evidence, replacement of the resident plastid genome by the alien genome occurs in the absence of intergenomic recombination. Our results provide a plausible mechanism for organelle capture in plants and suggest natural grafting as a path for horizontal gene and genome transfer between sexually incompatible species. PMID- 22308368 TI - Actin filament curvature biases branching direction. AB - Mechanical cues affect many important biological processes in metazoan cells, such as migration, proliferation, and differentiation. Such cues are thought to be detected by specialized mechanosensing molecules linked to the cytoskeleton, an intracellular network of protein filaments that provide mechanical rigidity to the cell and drive cellular shape change. The most abundant such filament, actin, forms branched networks nucleated by the actin-related protein (Arp) 2/3 complex that support or induce membrane protrusions and display adaptive behavior in response to compressive forces. Here we show that filamentous actin serves in a mechanosensitive capacity itself, by biasing the location of actin branch nucleation in response to filament bending. Using an in vitro assay to measure branching from curved sections of immobilized actin filaments, we observed preferential branch formation by the Arp2/3 complex on the convex face of the curved filament. To explain this behavior, we propose a fluctuation gating model in which filament binding or branch nucleation by Arp2/3 occur only when a sufficiently large, transient, local curvature fluctuation causes a favorable conformational change in the filament, and we show with Monte Carlo simulations that this model can quantitatively account for our experimental data. We also show how the branching bias can reinforce actin networks in response to compressive forces. These results demonstrate how filament curvature can alter the interaction of cytoskeletal filaments with regulatory proteins, suggesting that direct mechanotransduction by actin may serve as a general mechanism for organizing the cytoskeleton in response to force. PMID- 22308369 TI - Cell-to-cell movement of plastids in plants. AB - Our objective was to test whether or not plastids and mitochondria, the two DNA containing organelles, move between cells in plants. As our experimental approach, we grafted two different species of tobacco, Nicotiana tabacum and Nicotiana sylvestris. Grafting triggers formation of new cell-to-cell contacts, creating an opportunity to detect cell-to-cell organelle movement between the genetically distinct plants. We initiated tissue culture from sliced graft junctions and selected for clonal lines in which gentamycin resistance encoded in the N. tabacum nucleus was combined with spectinomycin resistance encoded in N. sylvestris plastids. Here, we present evidence for cell-to-cell movement of the entire 161-kb plastid genome in these plants, most likely in intact plastids. We also found that the related mitochondria were absent, suggesting independent movement of the two DNA-containing organelles. Acquisition of plastids from neighboring cells provides a mechanism by which cells may be repopulated with functioning organelles. Our finding supports the universality of intercellular organelle trafficking and may enable development of future biotechnological applications. PMID- 22308370 TI - Glucose activates free fatty acid receptor 1 gene transcription via phosphatidylinositol-3-kinase-dependent O-GlcNAcylation of pancreas-duodenum homeobox-1. AB - The G protein-coupled free fatty acid receptor-1 (FFA1/GPR40) plays a major role in the regulation of insulin secretion by fatty acids. GPR40 is considered a potential therapeutic target to enhance insulin secretion in type 2 diabetes; however, its mode of regulation is essentially unknown. The aims of this study were to test the hypothesis that glucose regulates GPR40 gene expression in pancreatic beta-cells and to determine the mechanisms of this regulation. We observed that glucose stimulates GPR40 gene transcription in pancreatic beta cells via increased binding of pancreas-duodenum homeobox-1 (Pdx-1) to the A-box in the HR2 region of the GPR40 promoter. Mutation of the Pdx-1 binding site within the HR2 abolishes glucose activation of GPR40 promoter activity. The stimulation of GPR40 expression and Pdx-1 binding to the HR2 in response to glucose are mimicked by N-acetyl glucosamine, an intermediate of the hexosamine biosynthesis pathway, and involve PI3K-dependent O-GlcNAcylation of Pdx-1 in the nucleus. We demonstrate that O-GlcNAc transferase (OGT) interacts with the product of the PI3K reaction, phosphatidylinositol 3,4,5-trisphosphate (PIP(3)), in the nucleus. This interaction enables OGT to catalyze O-GlcNAcylation of nuclear proteins, including Pdx-1. We conclude that glucose stimulates GPR40 gene expression at the transcriptional level through Pdx-1 binding to the HR2 region and via a signaling cascade that involves an interaction between OGT and PIP(3) at the nuclear membrane. These observations reveal a unique mechanism by which glucose metabolism regulates the function of transcription factors in the nucleus to induce gene expression. PMID- 22308371 TI - The human circadian metabolome. AB - The circadian clock orchestrates many aspects of human physiology, and disruption of this clock has been implicated in various pathologies, ranging from cancer to metabolic syndrome and diabetes. Although there is evidence that metabolism and the circadian clockwork are intimately linked on a transcriptional level, whether these effects are directly under clock control or are mediated by the rest activity cycle and the timing of food intake is unclear. To answer this question, we conducted an unbiased screen in human subjects of the metabolome of blood plasma and saliva at different times of day. To minimize indirect effects, subjects were kept in a 40-h constant routine of enforced posture, constant dim light, hourly isocaloric meals, and sleep deprivation. Under these conditions, we found that ~15% of all identified metabolites in plasma and saliva were under circadian control, most notably fatty acids in plasma and amino acids in saliva. Our data suggest that there is a strong direct effect of the endogenous circadian clock on multiple human metabolic pathways that is independent of sleep or feeding. In addition, they identify multiple potential small-molecule biomarkers of human circadian phase and sleep pressure. PMID- 22308372 TI - Phasic D1 and tonic D2 dopamine receptor signaling double dissociate the motivational effects of acute nicotine and chronic nicotine withdrawal. AB - Nicotine, the main psychoactive ingredient of tobacco smoke, induces negative motivational symptoms during withdrawal that contribute to relapse in dependent individuals. The neurobiological mechanisms underlying how the brain signals nicotine withdrawal remain poorly understood. Using electrophysiological, genetic, pharmacological, and behavioral methods, we demonstrate that tonic but not phasic activity is reduced during nicotine withdrawal in ventral tegmental area dopamine (DA) neurons, and that this pattern of signaling acts through DA D2 and adenosine A2A, but not DA D1, receptors. Selective blockade of phasic DA activity prevents the expression of conditioned place aversions to a single injection of nicotine in nondependent mice, but not to withdrawal from chronic nicotine in dependent mice, suggesting a shift from phasic to tonic dopaminergic mediation of the conditioned motivational response in nicotine dependent and withdrawn animals. Either increasing or decreasing activity at D2 or A2A receptors prevents the aversive motivational response to withdrawal from chronic nicotine, but not to acute nicotine. Modification of D1 receptor activity prevents the aversive response to acute nicotine, but not to nicotine withdrawal. This double dissociation demonstrates that the specific pattern of tonic DA activity at D2 receptors is a key mechanism in signaling the motivational effects experienced during nicotine withdrawal, and may represent a unique target for therapeutic treatments for nicotine addiction. PMID- 22308373 TI - Continuous and discontinuous quantum phase transitions in a model two-dimensional magnet. AB - The Shasty-Sutherland model, which consists of a set of spin 1/2 dimers on a 2D square lattice, is simple and soluble but captures a central theme of condensed matter physics by sitting precariously on the quantum edge between isolated, gapped excitations and collective, ordered ground states. We compress the model Shastry-Sutherland material, SrCu(2)(BO(3))(2), in a diamond anvil cell at cryogenic temperatures to continuously tune the coupling energies and induce changes in state. High-resolution X-ray measurements exploit what emerges as a remarkably strong spin-lattice coupling to both monitor the magnetic behavior and the absence or presence of structural discontinuities. In the low-pressure spin singlet regime, the onset of magnetism results in an expansion of the lattice with decreasing temperature, which permits a determination of the pressure dependent energy gap and the almost isotropic spin-lattice coupling energies. The singlet-triplet gap energy is suppressed continuously with increasing pressure, vanishing completely by 2 GPa. This continuous quantum phase transition is followed by a structural distortion at higher pressure. PMID- 22308374 TI - Ferric, not ferrous, heme activates RNA-binding protein DGCR8 for primary microRNA processing. AB - The RNA-binding protein DiGeorge Critical Region 8 (DGCR8) and its partner nuclease Drosha are essential for processing of microRNA (miRNA) primary transcripts (pri-miRNAs) in animals. Previous work showed that DGCR8 forms a highly stable and active complex with ferric [Fe(III)] heme using two endogenous cysteines as axial ligands. Here we report that reduction of the heme iron to the ferrous [Fe(II)] state in DGCR8 abolishes the pri-miRNA processing activity. The reduction causes a dramatic increase in the rate of heme dissociation from DGCR8, rendering the complex labile. Electronic absorption, magnetic circular dichroism, and resonance Raman spectroscopies indicate that reduction of the heme iron is accompanied by loss of the cysteines as axial ligands. ApoDGCR8 dimers, generated through reduction and removal of the heme, show low levels of activity in pri miRNA processing in vitro. Importantly, ferric, but not ferrous, heme restores the activity of apoDGCR8 to the level of the native ferric complex. This study demonstrates binding specificity of DGCR8 for ferric heme, provides direct biochemical evidence for ferric heme serving as an activator for miRNA maturation, and suggests that an intracellular environment increasing the availability of ferric heme may enhance the efficiency of pri-miRNA processing. PMID- 22308375 TI - High-resolution structure of a BRICHOS domain and its implications for anti amyloid chaperone activity on lung surfactant protein C. AB - BRICHOS domains are encoded in > 30 human genes, which are associated with cancer, neurodegeneration, and interstitial lung disease (ILD). The BRICHOS domain from lung surfactant protein C proprotein (proSP-C) is required for membrane insertion of SP-C and has anti-amyloid activity in vitro. Here, we report the 2.1 A crystal structure of the human proSP-C BRICHOS domain, which, together with molecular dynamics simulations and hydrogen-deuterium exchange mass spectrometry, reveals how BRICHOS domains may mediate chaperone activity. Observation of amyloid deposits composed of mature SP-C in lung tissue samples from ILD patients with mutations in the BRICHOS domain or in its peptide-binding linker region supports the in vivo relevance of the proposed mechanism. The results indicate that ILD mutations interfering with proSP-C BRICHOS activity cause amyloid disease secondary to intramolecular chaperone malfunction. PMID- 22308376 TI - Entropic origin of Mg2+-facilitated RNA folding. AB - Mg(2+) is essential for the proper folding and function of RNA, though the effect of Mg(2+) concentration on the free energy, enthalpy, and entropy landscapes of RNA folding is unknown. This work exploits temperature-controlled single-molecule FRET methods to address the thermodynamics of RNA folding pathways by probing the intramolecular docking/undocking kinetics of the ubiquitous GAAA tetraloop receptor tertiary interaction as a function of [Mg(2+)]. These measurements yield the barrier and standard state enthalpies, entropies, and free energies for an RNA tertiary transition, in particular, revealing the thermodynamic origin of [Mg(2+)]-facilitated folding. Surprisingly, these studies reveal that increasing [Mg(2+)] promotes tetraloop-receptor interaction by reducing the entropic barrier (-TDeltaS(++)(dock)) and the overall entropic penalty (-TDeltaS(+) (dock)) for docking, with essentially negligible effects on both the activation enthalpy (DeltaH(++)(dock)) and overall exothermicity (DeltaH(+)(dock)). These observations contrast with the conventional notion that increasing [Mg(2+)] facilitates folding by minimizing electrostatic repulsion of opposing RNA helices, which would incorrectly predict a decrease in DeltaH(++)(dock)) and DeltaH(+)(dock)) with [Mg(2+)]. Instead we propose that higher [Mg(2+)] can aid RNA folding by decreasing the entropic penalty of counterion uptake and by reducing disorder of the unfolded conformational ensemble. PMID- 22308378 TI - Mitochondrial ubiquitin ligase MITOL blocks S-nitrosylated MAP1B-light chain 1 mediated mitochondrial dysfunction and neuronal cell death. AB - Nitric oxide (NO) is implicated in neuronal cell survival. However, excessive NO production mediates neuronal cell death, in part via mitochondrial dysfunction. Here, we report that the mitochondrial ubiquitin ligase, MITOL, protects neuronal cells from mitochondrial damage caused by accumulation of S-nitrosylated microtubule-associated protein 1B-light chain 1 (LC1). S-nitrosylation of LC1 induces a conformational change that serves both to activate LC1 and to promote its ubiquination by MITOL, indicating that microtubule stabilization by LC1 is regulated through its interaction with MITOL. Excessive NO production can inhibit MITOL, and MITOL inhibition resulted in accumulation of S-nitrosylated LC1 following stimulation of NO production by calcimycin and N-methyl-D-aspartate. LC1 accumulation under these conditions resulted in mitochondrial dysfunction and neuronal cell death. Thus, the balance between LC1 activation by S-nitrosylation and down-regulation by MITOL is critical for neuronal cell survival. Our findings may contribute significantly to an understanding of the mechanisms of neurological diseases caused by nitrosative stress-mediated mitochondrial dysfunction. PMID- 22308377 TI - CD4 and CD8 T cells require different membrane gangliosides for activation. AB - Initial events of T-cell activation involve movement of the T-cell receptor into lipid rafts. Gangliosides are major components of lipid rafts. While investigating T-cell activation in ganglioside-deficient mice, we observed that CD4(+) and CD8(+) T cells required different ganglioside subsets for activation. Activation of CD4(+) T cells from GM3 synthase-null mice, deficient in GM3 derived gangliosides, is severely compromised, whereas CD8(+) T-cell activation is normal. Conversely, in cells from GM2/GD2 synthase-null mice, expressing only GM3 and GD3, CD4(+) T-cell activation is normal, whereas CD8(+) T-cell activation is deficient. Supplementing the cells with the corresponding missing gangliosides restores normal activation. GM3 synthase-null mice do not develop experimental asthma. Distinct expression patterns of ganglioside species in CD4(+) T and CD8(+) T cells, perhaps in uniquely functional lipid rafts, define immune functions in each T-cell subset. Control of ganglioside expression would offer a strategy targeting for specific T-cell subpopulations to treat immune diseases. PMID- 22308379 TI - Intermediate conductance calcium-activated potassium channels modulate summation of parallel fiber input in cerebellar Purkinje cells. AB - Encoding sensory input requires the expression of postsynaptic ion channels to transform key features of afferent input to an appropriate pattern of spike output. Although Ca(2+)-activated K(+) channels are known to control spike frequency in central neurons, Ca(2+)-activated K(+) channels of intermediate conductance (KCa3.1) are believed to be restricted to peripheral neurons. We now report that cerebellar Purkinje cells express KCa3.1 channels, as evidenced through single-cell RT-PCR, immunocytochemistry, pharmacology, and single-channel recordings. Furthermore, KCa3.1 channels coimmunoprecipitate and interact with low voltage-activated Cav3.2 Ca(2+) channels at the nanodomain level to support a previously undescribed transient voltage- and Ca(2+)-dependent current. As a result, subthreshold parallel fiber excitatory postsynaptic potentials (EPSPs) activate Cav3 Ca(2+) influx to trigger a KCa3.1-mediated regulation of the EPSP and subsequent after-hyperpolarization. The Cav3-KCa3.1 complex provides powerful control over temporal summation of EPSPs, effectively suppressing low frequencies of parallel fiber input. KCa3.1 channels thus contribute to a high-pass filter that allows Purkinje cells to respond preferentially to high-frequency parallel fiber bursts characteristic of sensory input. PMID- 22308380 TI - Crystal structures of two bacterial HECT-like E3 ligases in complex with a human E2 reveal atomic details of pathogen-host interactions. AB - In eukaryotes, ubiquitination is an important posttranslational process achieved through a cascade of ubiquitin-activating (E1), conjugating (E2), and ligase (E3) enzymes. Many pathogenic bacteria deliver virulence factors into the host cell that function as E3 ligases. How these bacterial "Trojan horses" integrate into the eukaryotic ubiquitin system has remained a mystery. Here we report crystal structures of two bacterial E3s, Salmonella SopA and Escherichia coli NleL, both in complex with human E2 UbcH7. These structures represent two distinct conformational states of the bacterial E3s, supporting the necessary structural rearrangements associated with ubiquitin transfer. The E2-interacting surface of SopA and NleL has little similarity to those of eukaryotic E3s. However, both bacterial E3s bind to the canonical surface of E2 that normally interacts with eukaryotic E3s. Furthermore, we show that a glutamate residue on E3 is involved in catalyzing ubiquitin transfer from E3 to the substrate, but not from E2 to E3. Together, these results provide mechanistic insights into the ubiquitin pathway and a framework for understanding molecular mimicry in bacterial pathogenesis. PMID- 22308381 TI - Severe mammal declines coincide with proliferation of invasive Burmese pythons in Everglades National Park. AB - Invasive species represent a significant threat to global biodiversity and a substantial economic burden. Burmese pythons, giant constricting snakes native to Asia, now are found throughout much of southern Florida, including all of Everglades National Park (ENP). Pythons have increased dramatically in both abundance and geographic range since 2000 and consume a wide variety of mammals and birds. Here we report severe apparent declines in mammal populations that coincide temporally and spatially with the proliferation of pythons in ENP. Before 2000, mammals were encountered frequently during nocturnal road surveys within ENP. In contrast, road surveys totaling 56,971 km from 2003-2011 documented a 99.3% decrease in the frequency of raccoon observations, decreases of 98.9% and 87.5% for opossum and bobcat observations, respectively, and failed to detect rabbits. Road surveys also revealed that these species are more common in areas where pythons have been discovered only recently and are most abundant outside the python's current introduced range. These findings suggest that predation by pythons has resulted in dramatic declines in mammals within ENP and that introduced apex predators, such as giant constrictors, can exert significant top-down pressure on prey populations. Severe declines in easily observed and/or common mammals, such as raccoons and bobcats, bode poorly for species of conservation concern, which often are more difficult to sample and occur at lower densities. PMID- 22308382 TI - Effective guidance of collective migration based on differences in cell states. AB - Directed cell migration is important for normal animal development and physiology. The process can also be subverted by tumor cells to invade other tissues and to metastasize. Some cells, such as leukocytes, migrate individually; other cells migrate together in groups or sheets, called collective cell migration. Guidance of individually migrating cells depends critically on subcellularly localized perception and transduction of signals. For collective cell migration, guidance could result from cells within a group achieving different signaling levels, with directionality then encoded in the collective rather than in individual cells. Here we subject this collective guidance hypothesis to direct tests, using migration of border cells during Drosophila oogenesis as our model system. These cells normally use two receptor tyrosine kinases (RTKs), PDGF/VEGF-related receptor (PVR) and EGFR, to read guidance cues secreted by the oocyte. Elevated but delocalized RTK signaling in one cell of the cluster was achieved by overexpression of PVR in the absence of ligand or by overexpression of fusion receptors unable to detect Drosophila ligands; alternatively, Rac was photoactivated centrally within a single cell. In each case, one cell within the group was in a high signal state, whereas others were in low signal states. The high signal cell directed cluster movement effectively. We conclude that differences in cell signaling states are sufficient to direct collective migration and are likely a substantial contributor to normal guidance. Cell signaling states could manifest as differences in gene expression or metabolite levels and thus differ substantially from factors normally considered when analyzing eukaryotic cell guidance. PMID- 22308383 TI - Synthetic model of the asymmetric [Mn3CaO4] cubane core of the oxygen-evolving complex of photosystem II. AB - The laboratory synthesis of the oxygen-evolving complex (OEC) of photosystem II has been the objective of synthetic chemists since the early 1970s. However, the absence of structural information on the OEC has hampered these efforts. Crystallographic reports on photosystem II that have been appearing at ever improving resolution over the past ten years have finally provided invaluable structural information on the OEC and show that it comprises a [Mn(3)CaO(4)] distorted cubane, to which is attached a fourth, external Mn atom, and the whole unit attached to polypeptides primarily by aspartate and glutamate carboxylate groups. Such a heterometallic Mn/Ca cubane with an additional metal attached to it has been unknown in the literature. This paper reports the laboratory synthesis of such an asymmetric cubane-containing compound with a bound external metal atom, [(1)]. All peripheral ligands are carboxylate or carboxylic acid groups. Variable-temperature magnetic susceptibility data have established 1 to possess an S = 9/2 ground state. EPR spectroscopy confirms this, and the Davies electron nuclear double resonance data reveal similar hyperfine couplings to those of other Mn(IV) species, including the OEC S(2) state. Comparison of the X ray absorption data with those for the OEC reveal 1 to possess structural parameters that make it a close structural model of the asymmetric-cubane OEC unit. This geometric and electronic structural correspondence opens up a new front in the multidisciplinary study of the properties and function of this important biological unit. PMID- 22308384 TI - Ancestral capture of syncytin-Car1, a fusogenic endogenous retroviral envelope gene involved in placentation and conserved in Carnivora. AB - Syncytins are envelope protein genes of retroviral origin that have been captured for a function in placentation. Two such genes have already been identified in simians, two distinct, unrelated genes have been identified in Muridae, and a fifth gene has been identified in the rabbit. Here, we searched for similar genes in the Laurasiatheria clade, which diverged from Euarchontoglires--primates, rodents, and lagomorphs--shortly after mammalian radiation (100 Mya). In silico search for envelope protein genes with full-coding capacity within the dog and cat genomes identified several candidate genes, with one common to both species that displayed placenta-specific expression, which was revealed by RT-PCR analysis of a large panel of tissues. This gene belongs to a degenerate endogenous retroviral element, with precise proviral integration at a site common to dog and cat. Cloning of the gene for an ex vivo pseudotype assay showed fusogenicity on both dog and cat cells. In situ hybridization on placenta sections from both species showed specific expression at the level of the invasive fetal villi within the placental junctional zone, where trophoblast cells fuse into a syncytiotrophoblast layer to form the maternofetal interface. Finally, we show that the gene is conserved among a series of 26 Carnivora representatives, with evidence for purifying selection and conservation of fusogenic activity. The gene is not found in the Pholidota order and, therefore, it was captured before Carnivora radiation, between 60 and 85 Mya. This gene is the oldest syncytin gene identified to date, and it is the first in a new major clade of eutherian mammals. PMID- 22308385 TI - Light-driven oxygen production from superoxide by Mn-binding bacterial reaction centers. AB - One of the outstanding questions concerning the early Earth is how ancient phototrophs made the evolutionary transition from anoxygenic to oxygenic photosynthesis, which resulted in a substantial increase in the amount of oxygen in the atmosphere. We have previously demonstrated that reaction centers from anoxygenic photosynthetic bacteria can be modified to bind a redox-active Mn cofactor, thus gaining a key functional feature of photosystem II, which contains the site for water oxidation in cyanobacteria, algae, and plants [Thielges M, et al. (2005) Biochemistry 44:7389-7394]. In this paper, the Mn-binding reaction centers are shown to have a light-driven enzymatic function; namely, the ability to convert superoxide into molecular oxygen. This activity has a relatively high efficiency with a k(cat) of approximately 1 s(-1) that is significantly larger than typically observed for designed enzymes, and a K(m) of 35-40 MUM that is comparable to the value of 50 MUM for Mn-superoxide dismutase, which catalyzes a similar reaction. Unlike wild-type reaction centers, the highly oxidizing reaction centers are not stable in the light unless they have a bound Mn. The stability and enzymatic ability of this type of Mn-binding reaction centers would have provided primitive phototrophs with an environmental advantage before the evolution of organisms with a more complex Mn(4)Ca cluster needed to perform the multielectron reactions required to oxidize water. PMID- 22308386 TI - Memory B cells in the lung participate in protective humoral immune responses to pulmonary influenza virus reinfection. AB - After pulmonary virus infection, virus-binding B cells ectopically accumulate in the lung. However, their contribution to protective immunity against reinfecting viruses remains unknown. Here, we show the phenotypes and protective functions of virus-binding memory B cells that persist in the lung following pulmonary infection with influenza virus. A fraction of virus-binding B-cell population in the lung expressed surface markers for splenic mature memory B cells (CD73, CD80, and CD273) along with CD69 and CXCR3 that are up-regulated on lung effector/memory T cells. The lung B-cell population with memory phenotype persisted for more than 5 mo after infection, and on reinfection promptly differentiated into plasma cells that produced virus-neutralizing antibodies locally. This production of local IgG and IgA neutralizing antibody was correlated with reduced virus spread in adapted hosts. Our data demonstrates that infected lungs harbor a memory B-cell subset with distinctive phenotype and ability to provide protection against pulmonary virus reinfection. PMID- 22308387 TI - A novel lineage of myoviruses infecting cyanobacteria is widespread in the oceans. AB - Viruses infecting bacteria (phages) are thought to greatly impact microbial population dynamics as well as the genome diversity and evolution of their hosts. Here we report on the discovery of a novel lineage of tailed dsDNA phages belonging to the family Myoviridae and describe its first representative, S-TIM5, that infects the ubiquitous marine cyanobacterium, Synechococcus. The genome of this phage encodes an entirely unique set of structural proteins not found in any currently known phage, indicating that it uses lineage-specific genes for virion morphogenesis and represents a previously unknown lineage of myoviruses. Furthermore, among its distinctive collection of replication and DNA metabolism genes, it carries a mitochondrial-like DNA polymerase gene, providing strong evidence for the bacteriophage origin of the mitochondrial DNA polymerase. S-TIM5 also encodes an array of bacterial-like metabolism genes commonly found in phages infecting cyanobacteria including photosynthesis, carbon metabolism and phosphorus acquisition genes. This suggests a common gene pool and gene swapping of cyanophage-specific genes among different phage lineages despite distinct sets of structural and replication genes. All cytosines following purine nucleotides are methylated in the S-TIM5 genome, constituting a unique methylation pattern that likely protects the genome from nuclease degradation. This phage is abundant in the Red Sea and S-TIM5 gene homologs are widespread in the oceans. This unusual phage type is thus likely to be an important player in the oceans, impacting the population dynamics and evolution of their primary producing cyanobacterial hosts. PMID- 22308388 TI - Rabenosyn-5 defines the fate of the transferrin receptor following clathrin mediated endocytosis. AB - Cell surface receptors and other proteins internalize through diverse mechanisms at the plasma membrane and are sorted to different destinations. Different subpopulations of early endosomes have been described, raising the question of whether different internalization mechanisms deliver cargo into different subsets of early endosomes. To address this fundamental question, we developed a microscopy platform to detect the precise position of endosomes relative to the plasma membrane during the uptake of ligands. Axial resolution is maximized by concurrently applied total internal reflection fluorescence and epifluorescence structured light. We found that transferrin receptors are delivered selectively from clathrin-coated pits on the plasma membrane into a specific subpopulation of endosomes enriched in the multivalent Rab GTPase and phosphoinositide-binding protein Rabenosyn-5. Depletion of Rabenosyn-5, but not of other early endosomal proteins such as early endosome antigen 1, resulted in impaired transferrin uptake and lysosomal degradation of transferrin receptors. These studies reveal a critical role for Rabenosyn-5 in determining the fate of transferrin receptors internalized by clathrin-mediated endocytosis and, more broadly, a mechanism whereby the delivery of cargo from the plasma membrane into specific early endosome subpopulations is required for its appropriate intracellular traffic. PMID- 22308389 TI - Gating transitions in the selectivity filter region of a sodium channel are coupled to the domain IV voltage sensor. AB - Voltage-dependent ion channels are crucial for generation and propagation of electrical activity in biological systems. The primary mechanism for voltage transduction in these proteins involves the movement of a voltage-sensing domain (D), which opens a gate located on the cytoplasmic side. A distinct conformational change in the selectivity filter near the extracellular side has been implicated in slow inactivation gating, which is important for spike frequency adaptation in neural circuits. However, it remains an open question whether gating transitions in the selectivity filter region are also actuated by voltage sensors. Here, we examine conformational coupling between each of the four voltage sensors and the outer pore of a eukaryotic voltage-dependent sodium channel. The voltage sensors of these sodium channels are not structurally symmetric and exhibit functional specialization. To track the conformational rearrangements of individual voltage-sensing domains, we recorded domain-specific gating pore currents. Our data show that, of the four voltage sensors, only the domain IV voltage sensor is coupled to the conformation of the selectivity filter region of the sodium channel. Trapping the outer pore in a particular conformation with a high-affinity toxin or disulphide crossbridge impedes the return of this voltage sensor to its resting conformation. Our findings directly establish that, in addition to the canonical electromechanical coupling between voltage sensor and inner pore gates of a sodium channel, gating transitions in the selectivity filter region are also coupled to the movement of a voltage sensor. Furthermore, our results also imply that the voltage sensor of domain IV is unique in this linkage and in the ability to initiate slow inactivation in sodium channels. PMID- 22308390 TI - Bifidobacterial surface-exopolysaccharide facilitates commensal-host interaction through immune modulation and pathogen protection. AB - Bifidobacteria comprise a significant proportion of the human gut microbiota. Several bifidobacterial strains are currently used as therapeutic interventions, claiming various health benefits by acting as probiotics. However, the precise mechanisms by which they maintain habitation within their host and consequently provide these benefits are not fully understood. Here we show that Bifidobacterium breve UCC2003 produces a cell surface-associated exopolysaccharide (EPS), the biosynthesis of which is directed by either half of a bidirectional gene cluster, thus leading to production of one of two possible EPSs. Alternate transcription of the two opposing halves of this cluster appears to be the result of promoter reorientation. Surface EPS provided stress tolerance and promoted in vivo persistence, but not initial colonization. Marked differences were observed in host immune response: strains producing surface EPS (EPS(+)) failed to elicit a strong immune response compared with EPS-deficient variants. Specifically, EPS production was shown to be linked to the evasion of adaptive B-cell responses. Furthermore, presence of EPS(+) B. breve reduced colonization levels of the gut pathogen Citrobacter rodentium. Our data thus assigns a pivotal and beneficial role for EPS in modulating various aspects of bifidobacterial-host interaction, including the ability of commensal bacteria to remain immunologically silent and in turn provide pathogen protection. This finding enforces the probiotic concept and provides mechanistic insights into health-promoting benefits for both animal and human hosts. PMID- 22308391 TI - Transforming growth factor beta-activated kinase 1 (TAK1)-dependent checkpoint in the survival of dendritic cells promotes immune homeostasis and function. AB - Homeostatic control of dendritic cell (DC) survival is crucial for adaptive immunity, but the molecular mechanism is not well defined. Moreover, how DCs influence immune homeostasis under steady state remains unclear. Combining DC specific and -inducible deletion systems, we report that transforming growth factor beta-activated kinase 1 (TAK1) is an essential regulator of DC survival and immune system homeostasis and function. Deficiency of TAK1 in CD11c(+) cells induced markedly elevated apoptosis, leading to the depletion of DC populations, especially the CD8(+) and CD103(+) DC subsets in lymphoid and nonlymphoid tissues, respectively. TAK1 also contributed to DC development by promoting the generation of DC precursors. Prosurvival signals from Toll-like receptors, CD40 and receptor activator of nuclear factor-kappaB (RANK) are integrated by TAK1 in DCs, which in turn mediated activation of downstream NF-kappaB and AKT-Foxo pathways and established a gene-expression program. TAK1 deficiency in DCs caused a myeloid proliferative disorder characterized by expansion of neutrophils and inflammatory monocytes, disrupted T-cell homeostasis, and prevented effective T cell priming and generation of regulatory T cells. Moreover, TAK1 signaling in DCs was required to prevent myeloid proliferation even in the absence of lymphocytes, indicating a previously unappreciated regulatory mechanism of DC mediated control of myeloid cell-dependent inflammation. Therefore, TAK1 orchestrates a prosurvival checkpoint in DCs that affects the homeostasis and function of the immune system. PMID- 22308392 TI - Hierarchical processing of complex motion along the primate dorsal visual pathway. AB - Neurons in the medial superior temporal (MST) area of the primate visual cortex respond selectively to complex motion patterns defined by expansion, rotation, and deformation. Consequently they are often hypothesized to be involved in important behavioral functions, such as encoding the velocities of moving objects and surfaces relative to the observer. However, the computations underlying such selectivity are unknown. In this work we have developed a unique, naturalistic motion stimulus and used it to probe the complex selectivity of MST neurons. The resulting data were then used to estimate the properties of the feed-forward inputs to each neuron. This analysis yielded models that successfully accounted for much of the observed stimulus selectivity, provided that the inputs were combined via a nonlinear integration mechanism that approximates a multiplicative interaction among MST inputs. In simulations we found that this type of integration has the functional role of improving estimates of the 3D velocity of moving objects. As this computation is of general utility for detecting complex stimulus features, we suggest that it may represent a fundamental aspect of hierarchical sensory processing. PMID- 22308393 TI - Identification of residues defining phospholipid flippase substrate specificity of type IV P-type ATPases. AB - Type IV P-type ATPases (P4-ATPases) catalyze translocation of phospholipid across a membrane to establish an asymmetric bilayer structure with phosphatidylserine (PS) and phosphatidylethanolamine (PE) restricted to the cytosolic leaflet. The mechanism for how P4-ATPases recognize and flip phospholipid is unknown, and is described as the "giant substrate problem" because the canonical substrate binding pockets of homologous cation pumps are too small to accommodate a bulky phospholipid. Here, we identify residues that confer differences in substrate specificity between Drs2 and Dnf1, Saccharomyces cerevisiae P4-ATPases that preferentially flip PS and phosphatidylcholine (PC), respectively. Transplanting transmembrane segments 3 and 4 (TM3-4) of Drs2 into Dnf1 alters the substrate preference of Dnf1 from PC to PS. Acquisition of the PS substrate maps to a Tyr618Phe substitution in TM4 of Dnf1, representing the loss of a single hydroxyl group. The reciprocal Phe511Tyr substitution in Drs2 specifically abrogates PS recognition by this flippase causing PS exposure on the outer leaflet of the plasma membrane without disrupting PE asymmetry. TM3 and the adjoining lumenal loop contribute residues important for Dnf1 PC preference, including Phe587. Modeling of residues involved in substrate selection suggests a novel P-type ATPase transport pathway at the protein/lipid interface and a potential solution to the giant substrate problem. PMID- 22308394 TI - Structure of saposin A lipoprotein discs. AB - The saposins are small, membrane-active proteins that exist in both soluble and lipid-bound states. Saposin A has roles in sphingolipid catabolism and transport and is required for the breakdown of galactosylceramide by beta galactosylceramidase. In the absence of lipid, saposin A adopts a closed monomeric apo conformation typical of this family. To study a lipid-bound state of this protein, we determined the crystal structure of saposin A in the presence of detergent to 1.9 A resolution. The structure reveals two chains of saposin A in an open conformation encapsulating 40 internally bound detergent molecules organized in a highly ordered bilayer-like hydrophobic core. The complex provides a high-resolution view of a discoidal lipoprotein particle in which all of the internalized acyl chains are resolved. Saposin A lipoprotein discs exhibit limited selectivity with respect to the incorporated lipid, and can solubilize phospholipids, sphingolipids, and cholesterol into discrete, monodisperse particles with mass of approximately 27 kDa. These discs may be the smallest possible lipoprotein structures that are stabilized by lipid self-assembly. PMID- 22308395 TI - Skeletal muscle transcriptional coactivator PGC-1alpha mediates mitochondrial, but not metabolic, changes during calorie restriction. AB - Calorie restriction (CR) is a dietary intervention that extends lifespan and healthspan in a variety of organisms. CR improves mitochondrial energy production, fuel oxidation, and reactive oxygen species (ROS) scavenging in skeletal muscle and other tissues, and these processes are thought to be critical to the benefits of CR. PGC-1alpha is a transcriptional coactivator that regulates mitochondrial function and is induced by CR. Consequently, many of the mitochondrial and metabolic benefits of CR are attributed to increased PGC-1alpha activity. To test this model, we examined the metabolic and mitochondrial response to CR in mice lacking skeletal muscle PGC-1alpha (MKO). Surprisingly, MKO mice demonstrated a normal improvement in glucose homeostasis in response to CR, indicating that skeletal muscle PGC-1alpha is dispensable for the whole-body benefits of CR. In contrast, gene expression profiling and electron microscopy (EM) demonstrated that PGC-1alpha is required for the full CR-induced increases in mitochondrial gene expression and mitochondrial density in skeletal muscle. These results demonstrate that PGC-1alpha is a major regulator of the mitochondrial response to CR in skeletal muscle, but surprisingly show that neither PGC-1alpha nor mitochondrial biogenesis in skeletal muscle are required for the whole-body metabolic benefits of CR. PMID- 22308396 TI - Subcellular calcium dynamics in a whole-cell model of an atrial myocyte. AB - In this study, we present an innovative mathematical modeling approach that allows detailed characterization of Ca(2+) movement within the three-dimensional volume of an atrial myocyte. Essential aspects of the model are the geometrically realistic representation of Ca(2+) release sites and physiological Ca(2+) flux parameters, coupled with a computationally inexpensive framework. By translating nonlinear Ca(2+) excitability into threshold dynamics, we avoid the computationally demanding time stepping of the partial differential equations that are often used to model Ca(2+) transport. Our approach successfully reproduces key features of atrial myocyte Ca(2+) signaling observed using confocal imaging. In particular, the model displays the centripetal Ca(2+) waves that occur within atrial myocytes during excitation-contraction coupling, and the effect of positive inotropic stimulation on the spatial profile of the Ca(2+) signals. Beyond this validation of the model, our simulation reveals unexpected observations about the spread of Ca(2+) within an atrial myocyte. In particular, the model describes the movement of Ca(2+) between ryanodine receptor clusters within a specific z disk of an atrial myocyte. Furthermore, we demonstrate that altering the strength of Ca(2+) release, ryanodine receptor refractoriness, the magnitude of initiating stimulus, or the introduction of stochastic Ca(2+) channel activity can cause the nucleation of proarrhythmic traveling Ca(2+) waves. The model provides clinically relevant insights into the initiation and propagation of subcellular Ca(2+) signals that are currently beyond the scope of imaging technology. PMID- 22308397 TI - Kinesin-2 family in vertebrate ciliogenesis. AB - The differentiation of cilia is mediated by kinesin-driven transport. As the function of kinesins in vertebrate ciliogenesis is poorly characterized, we decided to determine the role of kinesin-2 family motors--heterotrimeric kinesin II and the homodimeric Kif17 kinesin--in zebrafish cilia. We report that kif17 is largely dispensable for ciliogenesis; kif17 homozygous mutant animals are viable and display subtle morphological defects of olfactory cilia only. In contrast to that, the kif3b gene, encoding a heterotrimeric kinesin subunit, is necessary for cilia differentiation in most tissues, although exceptions exist, and include photoreceptors and a subset of hair cells. Cilia of these cell types persist even in kif3b/kif17 double mutants. Although we have not observed a functional redundancy of kif3b and kif17, kif17 is able to substitute for kif3b in some cilia. In contrast to kif3b/kif17 double mutants, simultaneous interference with kif3b and kif3c leads to the complete loss of photoreceptor and hair cell cilia, revealing redundancy of function. This is in agreement with the idea that Kif3b and Kif3c motor subunits form complexes with Kif3a, but not with each other. Interestingly, kif3b mutant photoreceptor cilia differentiate with a delay, suggesting that kif3c, although redundant with kif3b at later stages of differentiation, is not active early in photoreceptor ciliogenesis. Consistent with that, the overexpression of kif3c in kif3b mutants rescues early photoreceptor cilia defects. These data reveal unexpected diversity of functional relationships between vertebrate ciliary kinesins, and show that the repertoire of kinesin motors changes in some cilia during their differentiation. PMID- 22308398 TI - Stage-specific functions of leukemia/lymphoma-related factor (LRF) in the transcriptional control of osteoclast development. AB - Cell fate determination is tightly regulated by transcriptional activators and repressors. Leukemia/lymphoma-related factor (LRF; encoded by Zbtb7a), known as a POK (POZ/BTB and Kruppel) family transcriptional repressor, is induced during the development of bone-resorbing osteoclasts, but the physiological significance of LRF in bone metabolism and the molecular mechanisms underlying the transcriptional regulation of osteoclastogenesis by LRF have not been elucidated. Here we show that LRF negatively regulates osteoclast differentiation by repressing nuclear factor of activated T cells c1 (NFATc1) induction in the early phase of osteoclast development, while positively regulating osteoclast-specific genes by functioning as a coactivator of NFATc1 in the bone resorption phase. The stage-specific distinct functions of LRF were demonstrated in two lines of conditional knockout mice in which LRF was deleted in the early or late phase of osteoclast development. Thus, this study shows that LRF plays stage-specific distinct roles in osteoclast differentiation, exemplifying the delicate transcriptional regulation at work in lineage commitment. PMID- 22308399 TI - Conserved role for the Dachshund protein with Drosophila Pax6 homolog Eyeless in insulin expression. AB - Members of the insulin family peptides have conserved roles in the regulation of growth and metabolism in a wide variety of metazoans. The Drosophila genome encodes seven insulin-like peptide genes, dilp1-7, and the most prominent dilps (dilp2, dilp3, and dilp5) are expressed in brain neurosecretory cells known as "insulin-producing cells" (IPCs). Although these dilps are expressed in the same cells, the expression of each dilp is regulated independently. However, the molecular mechanisms that regulate the expression of individual dilps in the IPCs remain largely unknown. Here, we show that Dachshund (Dac), which is a highly conserved nuclear protein, is a critical transcription factor that specifically regulates dilp5 expression. Dac was strongly expressed in IPCs throughout development. dac loss-of-function analyses revealed a severely reduced dilp5 expression level in young larvae. Dac interacted physically with the Drosophila Pax6 homolog Eyeless (Ey), and these proteins synergistically promoted dilp5 expression. In addition, the mammalian homolog of Dac, Dach1/2, facilitated the promoting action of Pax6 on the expression of islet hormone genes in cultured mammalian cells. These observations indicate the conserved role of Dac/Dach in controlling insulin expression in conjunction with Ey/Pax6. PMID- 22308400 TI - RNA virus microRNA that mimics a B-cell oncomiR. AB - MicroRNAs (miRNAs) are small RNAs that play a regulatory role in numerous and diverse eukaryotic cellular processes. Virus-encoded miRNAs have garnered much interest, although the functions of most remain to be deciphered. To date, readily detectable, evolutionarily conserved natural miRNAs have only been identified from viruses with DNA genomes. Combined with the fact that most miRNAs are generated from endonucleolytic cleavage of longer transcripts, this finding has led to a common conception that naturally occurring RNA viruses will not encode miRNAs to avoid unproductive cleavage of their genomes or mRNAs. Here we demonstrate that the bovine leukemia virus (BLV), a retrovirus with an RNA genome, encodes a conserved cluster of miRNAs that are transcribed by RNA polymerase III (pol III). Thus, the BLV miRNAs avoid the conundrum of genome/mRNA cleavage because only the subgenomic pol III transcripts are efficiently processed into miRNAs. BLV infection is strongly associated with B-cell tumors in cattle. Because most cells in BLV-associated tumors express little viral mRNAs or proteins, exactly how BLV contributes to tumorigenesis has remained a decades long unsolved mystery. One BLV miRNA, BLV-miR-B4, shares partial sequence identity and shared common targets with the host miRNA, miR-29. As miR-29 overexpression is associated with B-cell neoplasms that resemble BLV-associated tumors, our findings suggest a possible mechanism contributing to BLV-induced tumorigenesis. PMID- 22308401 TI - YAP1, the nuclear target of Hippo signaling, stimulates heart growth through cardiomyocyte proliferation but not hypertrophy. AB - Heart growth is tightly controlled so that the heart reaches a predetermined size. Fetal heart growth occurs through cardiomyocyte proliferation, whereas postnatal heart growth involves primarily physiological cardiomyocyte hypertrophy. The Hippo kinase cascade is an important regulator of organ growth. A major target of this kinase cascade is YAP1, a transcriptional coactivator that is inactivated by Hippo kinase activity. Here, we used both genetic gain and loss of Yap1 function to investigate its role in regulating proliferative and physiologic hypertrophic heart growth. Fetal Yap1 inactivation caused marked, lethal myocardial hypoplasia and decreased cardiomyocyte proliferation, whereas fetal activation of YAP1 stimulated cardiomyocyte proliferation. Enhanced proliferation was particularly dramatic in trabecular cardiomyocytes that normally exit from the cell cycle. Remarkably, YAP1 activation was sufficient to stimulate proliferation of postnatal cardiomyocytes, both in culture and in the intact heart. A dominant negative peptide that blocked YAP1 binding to TEAD transcription factors inhibited YAP1 proliferative activity, indicating that this activity requires YAP1-TEAD interaction. Although Yap1 was a critical regulator of cardiomyocyte proliferation, it did not influence physiological hypertrophic growth of cardiomyocytes, because postnatal Yap1 gain or loss of function did not significantly alter cardiomyocyte size. These studies demonstrate that Yap1 is a crucial regulator of cardiomyocyte proliferation, cardiac morphogenesis, and myocardial trabeculation. Activation of Yap1 in postnatal cardiomyocytes may be a useful strategy to stimulate cardiomyocyte expansion in therapeutic myocardial regeneration. PMID- 22308402 TI - Host RNAs, including transposons, are encapsidated by a eukaryotic single stranded RNA virus. AB - Next-generation sequencing is a valuable tool in our growing understanding of the genetic diversity of viral populations. Using this technology, we have investigated the RNA content of a purified nonenveloped single-stranded RNA virus, flock house virus (FHV). We have also investigated the RNA content of virus-like particles (VLPs) of FHV and the related Nudaurelia capensis omega virus. VLPs predominantly package ribosomal RNA and transcripts of their baculoviral expression vectors. In addition, we find that 5.3% of the packaged RNAs are transposable elements derived from the Sf21 genome. This observation may be important when considering the therapeutic use of VLPs. We find that authentic FHV virions also package a variety of host RNAs, accounting for 1% of the packaged nucleic acid. Significant quantities of host messenger RNAs, ribosomal RNA, noncoding RNAs, and transposable elements are readily detected. The packaging of these host RNAs elicits the possibility of horizontal gene transfer between eukaryotic hosts that share a viral pathogen. We conclude that the genetic content of nonenveloped RNA viruses is variable, not just by genome mutation, but also in the diversity of RNA transcripts that are packaged. PMID- 22308403 TI - Analysis of Gal4-directed transcription activation using Tra1 mutants selectively defective for interaction with Gal4. AB - Promoter-specific transcriptional activators (activators) stimulate transcription through direct interactions with one or more components of the transcription machinery, termed the "target." The identification of direct in vivo targets of activators has been a major challenge. Previous studies have provided evidence that the Tra1 subunit of the yeast SAGA (Spt-Ada-Gcn5-acetyltransferase) complex is the target of the yeast activator Gal4. However, several other general transcription factors, in particular the mediator complex, have also been implicated as Gal4 targets. Here we perform a large-scale genetic screen to derive and characterize tra1 alleles that are selectively defective for interaction with Gal4 in vivo [Gal4 interaction defective (GID) mutants]. In contrast to WT Tra1, Tra1 GID mutants are not recruited by Gal4 to the promoter and cannot support Gal4-directed transcription, demonstrating the essentiality of the Gal4-Tra1 interaction. In yeast strains expressing a Tra1 GID mutant, binding of Gal4 to the promoter is unexpectedly also diminished, indicating that Gal4 and Tra1 bind cooperatively. Consistent with cooperative binding, we demonstrate that the Gal4-Tra1 interaction occurs predominantly on the promoter and not off DNA. Finally, we show that although Tra1 is targeted by other activators, these interactions are unaffected by GID mutations, revealing an unanticipated specificity of the Gal4-Tra1 interaction. PMID- 22308404 TI - Strand swapping regulates the iron-sulfur cluster in the diabetes drug target mitoNEET. AB - MitoNEET is a recently identified diabetes drug target that coordinates a transferable 2Fe-2S cluster, and additionally contains an unusual strand swap. In this manuscript, we use a dual basin structure-based model to predict and characterize the folding and functionality of strand swapping in mitoNEET. We demonstrate that a strand unswapped conformation is kinetically accessible and that multiple levels of control are employed to regulate the conformational dynamics of the system. Environmental factors such as temperature can shift route preference toward the unswapped pathway. Additionally we see that a region recently identified as contributing to frustration in folding acts as a regulatory hinge loop that modulates conformational balance. Interestingly, strand unswapping transfers strain specifically to cluster-coordinating residues, opening the cluster-coordinating pocket. Strengthening contacts within the cluster-coordinating pocket opens a new pathway between the swapped and unswapped conformation that utilizes cracking to bypass the unfolded basin. These results suggest that local control within distinct regions affect motions important in regulating mitoNEET's 2Fe-2S clusters. PMID- 22308405 TI - Leghemoglobin green derivatives with nitrated hemes evidence production of highly reactive nitrogen species during aging of legume nodules. AB - Globins constitute a superfamily of proteins widespread in all kingdoms of life, where they fulfill multiple functions, such as efficient O(2) transport and modulation of nitric oxide bioactivity. In plants, the most abundant Hbs are the symbiotic leghemoglobins (Lbs) that scavenge O(2) and facilitate its diffusion to the N(2)-fixing bacteroids in nodules. The biosynthesis of Lbs during nodule formation has been studied in detail, whereas little is known about the green derivatives of Lbs generated during nodule senescence. Here we characterize modified forms of Lbs, termed Lba(m), Lbc(m), and Lbd(m), of soybean nodules. These green Lbs have identical globins to the parent red Lbs but their hemes are nitrated. By combining UV-visible, MS, NMR, and resonance Raman spectroscopies with reconstitution experiments of the apoprotein with protoheme or mesoheme, we show that the nitro group is on the 4-vinyl. In vitro nitration of Lba with excess nitrite produced several isomers of nitrated heme, one of which is identical to those found in vivo. The use of antioxidants, metal chelators, and heme ligands reveals that nitration is contingent upon the binding of nitrite to heme Fe, and that the reactive nitrogen species involved derives from nitrous acid and is most probably the nitronium cation. The identification of these green Lbs provides conclusive evidence that highly oxidizing and nitrating species are produced in nodules leading to nitrosative stress. These findings are consistent with a previous report showing that the modified Lbs are more abundant in senescing nodules and have aberrant O(2) binding. PMID- 22308406 TI - Structural reorganization of the interleukin-7 signaling complex. AB - We report here an unliganded receptor structure in the common gamma-chain (gamma(c)) family of receptors and cytokines. The crystal structure of the unliganded form of the interleukin-7 alpha receptor (IL-7Ralpha) extracellular domain (ECD) at 2.15 A resolution reveals a homodimer forming an "X" geometry looking down onto the cell surface with the C termini of the two chains separated by 110 A and the dimer interface comprising residues critical for IL-7 binding. Further biophysical studies indicate a weak association of the IL-7Ralpha ECDs but a stronger association between the gamma(c)/IL-7Ralpha ECDs, similar to previous studies of the full-length receptors on CD4(+) T cells. Based on these and previous results, we propose a molecular mechanism detailing the progression from the inactive IL-7Ralpha homodimer and IL-7Ralpha-gamma(c) heterodimer to the active IL-7-IL-7Ralpha-gamma(c) ternary complex whereby the two receptors undergo at least a 90 degrees rotation away from the cell surface, moving the C termini of IL-7Ralpha and gamma(c) from a distance of 110 A to less than 30 A at the cell surface. This molecular mechanism can be used to explain recently discovered IL-7 and gamma(c)-independent gain-of-function mutations in IL-7Ralpha from B- and T cell acute lymphoblastic leukemia patients. The mechanism may also be applicable to other gamma(c) receptors that form inactive homodimers and heterodimers independent of their cytokines. PMID- 22308407 TI - The adenylyltransferase domain of bacterial Pnkp defines a unique RNA ligase family. AB - Pnkp is the end-healing and end-sealing component of an RNA repair system present in diverse bacteria from ten different phyla. To gain insight to the mechanism and evolution of this repair system, we determined the crystal structures of the ligase domain of Clostridium thermocellum Pnkp in three functional states along the reaction pathway: apoenzyme, ligase * ATP substrate complex, and covalent ligase-AMP intermediate. The tertiary structure is composed of a classical ligase nucleotidyltransferase module that is embellished by a unique alpha-helical insert module and a unique C-terminal alpha-helical module. Structure-guided mutational analysis identified active site residues essential for ligase adenylylation. Pnkp defines a new RNA ligase family with signature structural and functional properties. PMID- 22308408 TI - Differential modulation of the default mode network via serotonin-1A receptors. AB - Reflecting one's mental self is a fundamental process for evaluating the personal relevance of life events and for moral decision making and future envisioning. Although the corresponding network has been receiving growing attention, the driving neurochemical mechanisms of the default mode network (DMN) remain unknown. Here we combined positron emission tomography and functional magnetic resonance imaging to investigate modulations of the DMN via serotonin-1A receptors (5-HT(1A)), separated for 5-HT autoinhibition (dorsal raphe nucleus) and local inhibition (heteroreceptors in projection areas). Using two independent approaches, regional 5-HT(1A) binding consistently predicted DMN activity in the retrosplenial cortex for resting-state functional magnetic resonance imaging and the Tower of London task. On the other hand, both local and autoinhibitory 5 HT(1A) binding inversely modulated the posterior cingulate cortex, the strongest hub in the resting human brain. In the frontal part of the DMN, a negative association was found between the dorsal medial prefrontal cortex and local 5 HT(1A) inhibition. Our results indicate a modulation of key areas involved in self-referential processing by serotonergic neurotransmission, whereas variations in 5-HT(1A) binding explained a considerable amount of the individual variability in the DMN. Moreover, the brain regions associated with distinct introspective functions seem to be specifically regulated by the different 5-HT(1A) binding sites. Together with previously reported modulations of dopamine and GABA, this regional specialization suggests complex interactions of several neurotransmitters driving the default mode network. PMID- 22308409 TI - Global kinetic analysis of proteolysis via quantitative targeted proteomics. AB - Mass spectrometry-based proteomics is a powerful tool for identifying hundreds to thousands of posttranslational modifications in complex mixtures. However, it remains enormously challenging to simultaneously assess the intrinsic catalytic efficiencies (k(cat)/K(M)) of these modifications in the context of their natural interactors. Such fundamental enzymological constants are key to determining substrate specificity and for establishing the timing and importance of cellular signaling. Here, we report the use of selected reaction monitoring (SRM) for tracking proteolysis induced by human apoptotic caspases-3, -7, -8, and -9 in lysates and living cells. By following the appearance of the cleaved peptides in lysate as a function of time, we were able to determine hundreds of catalytic efficiencies in parallel. Remarkably, we find the rates of substrate hydrolysis for individual caspases vary greater than 500-fold indicating a sequential process. Moreover, the rank-order of substrate cutting is similar in apoptotic cells, suggesting that cellular structures do not dramatically alter substrate accessibility. Comparisons of extrinsic (TRAIL) and intrinsic (staurosporine) inducers of apoptosis revealed similar substrate profiles, suggesting the final proteolytic demolitions proceed by similarly ordered plans. Certain biological processes were rapidly targeted by the caspases, including multiple components of the endocyotic pathway and miRNA processing machinery. We believe this massively parallel and quantitative label-free approach to obtaining basic enzymological constants will facilitate the study of proteolysis and other posttranslational modifications in complex mixtures. PMID- 22308410 TI - Ribosome clearance by FusB-type proteins mediates resistance to the antibiotic fusidic acid. AB - Resistance to the antibiotic fusidic acid (FA) in the human pathogen Staphylococcus aureus usually results from expression of FusB-type proteins (FusB or FusC). These proteins bind to elongation factor G (EF-G), the target of FA, and rescue translation from FA-mediated inhibition by an unknown mechanism. Here we show that the FusB family are two-domain metalloproteins, the C-terminal domain of which contains a four-cysteine zinc finger with a unique structural fold. This domain mediates a high-affinity interaction with the C-terminal domains of EF-G. By binding to EF-G on the ribosome, FusB-type proteins promote the dissociation of stalled ribosome?EF-G?GDP complexes that form in the presence of FA, thereby allowing the ribosomes to resume translation. Ribosome clearance by these proteins represents a highly unusual antibiotic resistance mechanism, which appears to be fine-tuned by the relative abundance of FusB-type protein, ribosomes, and EF-G. PMID- 22308411 TI - Amphotericin primarily kills yeast by simply binding ergosterol. AB - Amphotericin B (AmB) is a prototypical small molecule natural product that can form ion channels in living eukaryotic cells and has remained refractory to microbial resistance despite extensive clinical utilization in the treatment of life-threatening fungal infections for more than half a century. It is now widely accepted that AmB kills yeast primarily via channel-mediated membrane permeabilization. Enabled by the iterative cross-coupling-based synthesis of a functional group deficient derivative of this natural product, we have discovered that channel formation is not required for potent fungicidal activity. Alternatively, AmB primarily kills yeast by simply binding ergosterol, a lipid that is vital for many aspects of yeast cell physiology. Membrane permeabilization via channel formation represents a second complementary mechanism that further increases drug potency and the rate of yeast killing. Collectively, these findings (i) reveal that the binding of a physiologically important microbial lipid is a powerful and clinically validated antimicrobial strategy that may be inherently refractory to resistance, (ii) illuminate a more straightforward path to an improved therapeutic index for this clinically vital but also highly toxic antifungal agent, and (iii) suggest that the capacity for AmB to form protein-like ion channels might be separable from its cytocidal effects. PMID- 22308412 TI - Auditory circuit in the Drosophila brain. AB - Most animals exhibit innate auditory behaviors driven by genetically hardwired neural circuits. In Drosophila, acoustic information is relayed by Johnston organ neurons from the antenna to the antennal mechanosensory and motor center (AMMC) in the brain. Here, by using structural connectivity analysis, we identified five distinct types of auditory projection neurons (PNs) interconnecting the AMMC, inferior ventrolateral protocerebrum (IVLP), and ventrolateral protocerebrum (VLP) regions of the central brain. These auditory PNs are also functionally distinct; AMMC-B1a, AMMC-B1b, and AMMC-A2 neurons differ in their responses to sound (i.e., they are narrowly tuned or broadly tuned); one type of audioresponsive IVLP commissural PN connecting the two hemispheres is GABAergic; and one type of IVLP-VLP PN acts as a generalist responding to all tested audio frequencies. Our findings delineate an auditory processing pathway involving AMMC >IVLP->VLP in the Drosophila brain. PMID- 22308413 TI - How Christians reconcile their personal political views and the teachings of their faith: projection as a means of dissonance reduction. AB - The present study explores the dramatic projection of one's own views onto those of Jesus among conservative and liberal American Christians. In a large-scale survey, the relevant views that each group attributed to a contemporary Jesus differed almost as much as their own views. Despite such dissonance-reducing projection, however, conservatives acknowledged the relevant discrepancy with regard to "fellowship" issues (e.g., taxation to reduce economic inequality and treatment of immigrants) and liberals acknowledged the relevant discrepancy with regard to "morality" issues (e.g., abortion and gay marriage). However, conservatives also claimed that a contemporary Jesus would be even more conservative than themselves on the former issues whereas liberals claimed that Jesus would be even more liberal than themselves on the latter issues. Further reducing potential dissonance, liberal and conservative Christians differed markedly in the types of issues they claimed to be more central to their faith. A concluding discussion considers the relationship between individual motivational processes and more social processes that may underlie the present findings, as well as implications for contemporary social and political conflict. PMID- 22308414 TI - Control of target gene specificity during metamorphosis by the steroid response gene E93. AB - Hormonal control of sexual maturation is a common feature in animal development. A particularly dramatic example is the metamorphosis of insects, in which pulses of the steroid hormone ecdysone drive the wholesale transformation of the larva into an adult. The mechanisms responsible for this transformation are not well understood. Work in Drosophila indicates that the larval and adult forms are patterned by the same underlying sets of developmental regulators, but it is not understood how the same regulators pattern two distinct forms. Recent studies indicate that this ability is facilitated by a global change in the responsiveness of target genes during metamorphosis. Here we show that this shift is controlled in part by the ecdysone-induced transcription factor E93. Although long considered a dedicated regulator of larval cell death, we find that E93 is expressed widely in adult cells at the pupal stage and is required for many patterning processes at this time. To understand the role of E93 in adult patterning, we focused on a simple E93-dependent process, the induction of the Dll gene within bract cells of the pupal leg by EGF receptor signaling. In this system, we show that E93 functions to cause Dll to become responsive to EGF receptor signaling. We demonstrate that E93 is both necessary and sufficient for directing this switch. E93 likely controls the responsiveness of many other target genes because it is required broadly for patterning during metamorphosis. The wide conservation of E93 orthologs suggests that similar mechanisms control life-cycle transitions in other organisms, including vertebrates. PMID- 22308415 TI - Task reward structure shapes rapid receptive field plasticity in auditory cortex. AB - As sensory stimuli and behavioral demands change, the attentive brain quickly identifies task-relevant stimuli and associates them with appropriate motor responses. The effects of attention on sensory processing vary across task paradigms, suggesting that the brain may use multiple strategies and mechanisms to highlight attended stimuli and link them to motor action. To better understand factors that contribute to these variable effects, we studied sensory representations in primary auditory cortex (A1) during two instrumental tasks that shared the same auditory discrimination but required different behavioral responses, either approach or avoidance. In the approach task, ferrets were rewarded for licking a spout when they heard a target tone amid a sequence of reference noise sounds. In the avoidance task, they were punished unless they inhibited licking to the target. To explore how these changes in task reward structure influenced attention-driven rapid plasticity in A1, we measured changes in sensory neural responses during behavior. Responses to the target changed selectively during both tasks but did so with opposite sign. Despite the differences in sign, both effects were consistent with a general neural coding strategy that maximizes discriminability between sound classes. The dependence of the direction of plasticity on task suggests that representations in A1 change not only to sharpen representations of task-relevant stimuli but also to amplify responses to stimuli that signal aversive outcomes and lead to behavioral inhibition. Thus, top-down control of sensory processing can be shaped by task reward structure in addition to the required sensory discrimination. PMID- 22308416 TI - Decreased osteoclastogenesis in serotonin-deficient mice. AB - Peripheral serotonin, synthesized by tryptophan hydroxylase-1 (TPH(1)), has been shown to play a key role in several physiological functions. Recently, controversy has emerged about whether peripheral serotonin has any effect on bone density and remodeling.We therefore decided to investigate in detail bone remodeling in growing and mature TPH(1) knockout mice (TPH(1)(-/-)). Bone resorption in TPH(1)(-/-) mice, as assessed by biochemical markers and bone histomorphometry, was markedly decreased at both ages. Using bone marrow transplantation, we present evidence that the decrease in bone resorption in TPH(1)(-/-) mice is cell-autonomous. Cultures from TPH(1)(-/-) in the presence of macrophage colony-stimulating factor and receptor activator for NF-KB ligand (RANKL) displayed fewer osteoclasts, and the decreased differentiation could be rescued by adding serotonin. Our data also provide evidence that in the presence of RANKL, osteoclast precursors express TPH(1) and synthesize serotonin. Furthermore, pharmacological inhibition of serotonin receptor 1B with SB224289, and of receptor 2A with ketanserin, also reduced the number of osteoclasts. Our findings reveal that serotonin has an important local action in bone, as it can amplify the effect of RANKL on osteoclastogenesis. PMID- 22308417 TI - Molecular architecture of the multisubunit homotypic fusion and vacuole protein sorting (HOPS) tethering complex. AB - Membrane fusion within the eukaryotic endomembrane system depends on the initial recognition of Rab GTPase on transport vesicles by multisubunit tethering complexes and subsequent coupling to SNARE-mediated fusion. The conserved vacuolar/lysosomal homotypic fusion and vacuole protein sorting (HOPS) tethering complex combines both activities. Here we present the overall structure of the fusion-active HOPS complex. Our data reveal a flexible ~30-nm elongated seahorse like structure, which can adopt contracted and elongated shapes. Surprisingly, both ends of the HOPS complex contain a Rab-binding subunit: Vps41 and Vps39. The large head contains in addition to Vps41 the SNARE-interacting Vps33, whereas Vps39 is found in the bulky tip of its tail. Vps11 and Vps18 connect head and tail. Our data suggest that HOPS bridges Ypt7-positive membranes and chaperones SNAREs at fusion sites. PMID- 22308418 TI - Integrated cross-species transcriptional network analysis of metastatic susceptibility. AB - Metastatic disease is the proximal cause of mortality for most cancers and remains a significant problem for the clinical management of neoplastic disease. Recent advances in global transcriptional analysis have enabled better prediction of individuals likely to progress to metastatic disease. However, minimal overlap between predictive signatures has precluded easy identification of key biological processes contributing to the prometastatic transcriptional state. To overcome this limitation, we have applied network analysis to two independent human breast cancer datasets and three different mouse populations developed for quantitative analysis of metastasis. Analysis of these datasets revealed that the gene membership of the networks is highly conserved within and between species, and that these networks predicted distant metastasis free survival. Furthermore these results suggest that susceptibility to metastatic disease is cell-autonomous in estrogen receptor-positive tumors and associated with the mitotic spindle checkpoint. In contrast, nontumor genetics and pathway activities-associated stromal biology are significant modifiers of the rate of metastatic spread of estrogen receptor-negative tumors. These results suggest that the application of network analysis across species may provide a robust method to identify key biological programs associated with human cancer progression. PMID- 22308419 TI - Environmental stress increases the entry of cytoplasmic organellar DNA into the nucleus in plants. AB - Mitochondria and chloroplasts (photosynthetic members of the plastid family of cytoplasmic organelles) in eukaryotic cells originated more than a billion years ago when an ancestor of the nucleated cell engulfed two different prokaryotes in separate sequential events. Extant cytoplasmic organellar genomes contain very few genes compared with their candidate free-living ancestors, as most have functionally relocated to the nucleus. The first step in functional relocation involves the integration of inactive DNA fragments into nuclear chromosomes, and this process continues at high frequency with attendant genetic, genomic, and evolutionary consequences. Using two different transplastomic tobacco lines, we show that DNA migration from chloroplasts to the nucleus is markedly increased by mild heat stress. In addition, we show that insertion of mitochondrial DNA fragments during the repair of induced double-strand breaks is increased by heat stress. The experiments demonstrate that the nuclear influx of organellar DNA is a potentially a source of mutation for nuclear genomes that is highly susceptible to temperature fluctuations that are well within the range experienced naturally. PMID- 22308420 TI - Detailing the optimality of photosynthesis in cyanobacteria through systems biology analysis. AB - Photosynthesis has recently gained considerable attention for its potential role in the development of renewable energy sources. Optimizing photosynthetic organisms for biomass or biofuel production will therefore require a systems understanding of photosynthetic processes. We reconstructed a high-quality genome scale metabolic network for Synechocystis sp. PCC6803 that describes key photosynthetic processes in mechanistic detail. We performed an exhaustive in silico analysis of the reconstructed photosynthetic process under different light and inorganic carbon (Ci) conditions as well as under genetic perturbations. Our key results include the following. (i) We identified two main states of the photosynthetic apparatus: a Ci-limited state and a light-limited state. (ii) We discovered nine alternative electron flow pathways that assist the photosynthetic linear electron flow in optimizing the photosynthesis performance. (iii) A high degree of cooperativity between alternative pathways was found to be critical for optimal autotrophic metabolism. Although pathways with high photosynthetic yield exist for optimizing growth under suboptimal light conditions, pathways with low photosynthetic yield guarantee optimal growth under excessive light or Ci limitation. (iv) Photorespiration was found to be essential for the optimal photosynthetic process, clarifying its role in high-light acclimation. Finally, (v) an extremely high photosynthetic robustness drives the optimal autotrophic metabolism at the expense of metabolic versatility and robustness. The results and modeling approach presented here may promote a better understanding of the photosynthetic process. They can also guide bioengineering projects toward optimal biofuel production in photosynthetic organisms. PMID- 22308422 TI - Bright illusions reduce the eye's pupil. AB - We recorded by use of an infrared eye-tracker the pupil diameters of participants while they observed visual illusions of lightness or brightness. Four original illusions {based on Gaetano Kanisza's [Kanizsa G (1976) Subjective contours. Sci Am 234:48-52] and Akiyoshi Kitaoka's [Kitaoka A. (2005) Trick Eyes (Barnes & Noble, New Providence, NJ).] examples} were manipulated to obtain control conditions in which the perceived illusory luminance was either eliminated or reduced. All stimuli were equiluminant so that constrictions in pupillary size could not be ascribed to changes in light energy. We found that the pupillary diameter rapidly varied according to perceived brightness and lightness strength. Differences in local contrast information could be ruled out as an explanation because, in a second experiment, the observers maintained eye fixation in the center of the display; thus, differential stimulation of the fovea by local contrast changes could not be responsible for the pupillary differences. Hence, the most parsimonious explanation for the present findings is that pupillary responses to ambient light reflect the perceived brightness or lightness of the scene and not simply the amount of physical light energy entering the eye. Thus, the pupillary physiological response reflects the subjective perception of light and supports the idea that the brain's visual circuitry is shaped by visual experience with images and their possible sources. PMID- 22308421 TI - Maternal support in early childhood predicts larger hippocampal volumes at school age. AB - Early maternal support has been shown to promote specific gene expression, neurogenesis, adaptive stress responses, and larger hippocampal volumes in developing animals. In humans, a relationship between psychosocial factors in early childhood and later amygdala volumes based on prospective data has been demonstrated, providing a key link between early experience and brain development. Although much retrospective data suggests a link between early psychosocial factors and hippocampal volumes in humans, to date there has been no prospective data to inform this potentially important public health issue. In a longitudinal study of depressed and healthy preschool children who underwent neuroimaging at school age, we investigated whether early maternal support predicted later hippocampal volumes. Maternal support observed in early childhood was strongly predictive of hippocampal volume measured at school age. The positive effect of maternal support on hippocampal volumes was greater in nondepressed children. These findings provide prospective evidence in humans of the positive effect of early supportive parenting on healthy hippocampal development, a brain region key to memory and stress modulation. PMID- 22308423 TI - Soft currencies, cash economies, new monies: past and present. AB - Current variation in the forms of money challenges economic anthropologists and historians to review theory and comparative findings on multiple currency systems. There are four main sections to the paper devoted to (i) the present continuum of hard to soft currencies as an instance of multiplicity, including discussion of different combinations of the classic four functions of money, especially the relationship between store of value and medium of exchange; (ii) the logic of anthropological inquiry into multiple currency economies; (iii) the case of the monies of Atlantic Africa, applying the analytics of exchange rates as conversions to African transactions; and (iv) the return to economic life in a present day Nigerian economy lived in soft currency and cash. The paper identifies five findings that suggest foci for future research. (i) The widespread occurrence of conversions, which bring together ranking principles within transactions. (ii) Several types of positional ranking ranging from simple stepwise ordinal scales to iconic ordinality that creates a parabolic curve of value. (iii) Fictional units of account that serve to mediate both the memorization of nonreductive transactions and their nature as conversions. (iv) The importance of the temporal reach of what constitutes wealth: over the short run, the life span, intergenerational succession, and in (legal) perpetuity (as for corporate and sovereign debts and specified assets). (v) The social niches in which these qualities are brought together in transactional regimes. In conclusion, the paper returns to the exchange function of cash, soft currencies, and new money forms. PMID- 22308424 TI - Comparative metatranscriptomics identifies molecular bases for the physiological responses of phytoplankton to varying iron availability. AB - In vast expanses of the oceans, growth of large phytoplankton such as diatoms is limited by iron availability. Diatoms respond almost immediately to the delivery of iron and rapidly compose the majority of phytoplankton biomass. The molecular bases underlying the subsistence of diatoms in iron-poor waters and the plankton community dynamics that follow iron resupply remain largely unknown. Here we use comparative metatranscriptomics to identify changes in gene expression associated with iron-stimulated growth of diatoms and other eukaryotic plankton. A microcosm iron-enrichment experiment using mixed-layer waters from the northeastern Pacific Ocean resulted in increased proportions of diatom transcripts and reduced proportions of transcripts from most other taxa within 98 h after iron addition. Hundreds of diatom genes were differentially expressed in the iron-enriched community compared with the iron-limited community; transcripts of diatom genes required for synthesis of photosynthesis and chlorophyll components, nitrate assimilation and the urea cycle, and synthesis of carbohydrate storage compounds were significantly overrepresented. Transcripts of genes encoding rhodopsins in eukaryotic phytoplankton were significantly underrepresented following iron enrichment, suggesting rhodopsins help cells cope with low-iron conditions. Oceanic diatoms appear to display a distinctive transcriptional response to iron enrichment that allows chemical reduction of available nitrogen and carbon sources along with a continued dependence on iron-free photosynthetic proteins rather than substituting for iron-containing functional equivalents present within their gene repertoire. This ability of diatoms to divert their newly acquired iron toward nitrate assimilation may underlie why diatoms consistently dominate iron enrichments in high-nitrate, low-chlorophyll regions. PMID- 22308425 TI - Defects in purine nucleotide metabolism lead to substantial incorporation of xanthine and hypoxanthine into DNA and RNA. AB - Deamination of nucleobases in DNA and RNA results in the formation of xanthine (X), hypoxanthine (I), oxanine, and uracil, all of which are miscoding and mutagenic in DNA and can interfere with RNA editing and function. Among many forms of nucleic acid damage, deamination arises from several unrelated mechanisms, including hydrolysis, nitrosative chemistry, and deaminase enzymes. Here we present a fourth mechanism contributing to the burden of nucleobase deamination: incorporation of hypoxanthine and xanthine into DNA and RNA caused by defects in purine nucleotide metabolism. Using Escherichia coli and Saccharomyces cerevisiae with defined mutations in purine metabolism in conjunction with analytical methods for quantifying deaminated nucleobases in DNA and RNA, we observed large increases (up to 600-fold) in hypoxanthine in both DNA and RNA in cells unable to convert IMP to XMP or AMP (IMP dehydrogenase, guaB; adenylosuccinate synthetase, purA, and ADE12), and unable to remove dITP/ITP and dXTP/XTP from the nucleotide pool (dITP/XTP pyrophosphohydrolase, rdgB and HAM1). Conversely, modest changes in xanthine levels were observed in RNA (but not DNA) from E. coli lacking purA and rdgB and the enzyme converting XMP to GMP (GMP synthetase, guaA). These observations suggest that disturbances in purine metabolism caused by known genetic polymorphisms could increase the burden of mutagenic deaminated nucleobases in DNA and interfere with gene expression and RNA function, a situation possibly exacerbated by the nitrosative stress of concurrent inflammation. The results also suggest a mechanistic basis for the pathophysiology of human inborn errors of purine nucleotide metabolism. PMID- 22308426 TI - Carbon availability triggers fungal nitrogen uptake and transport in arbuscular mycorrhizal symbiosis. AB - The arbuscular mycorrhizal (AM) symbiosis, formed between the majority of land plants and ubiquitous soil fungi of the phylum Glomeromycota, is responsible for massive nutrient transfer and global carbon sequestration. AM fungi take up nutrients from the soil and exchange them against photosynthetically fixed carbon (C) from the host. Recent studies have demonstrated that reciprocal reward strategies by plant and fungal partners guarantee a "fair trade" of phosphorus against C between partners [Kiers ET, et al. (2011) Science 333:880-882], but whether a similar reward mechanism also controls nitrogen (N) flux in the AM symbiosis is not known. Using mycorrhizal root organ cultures, we manipulated the C supply to the host and fungus and followed the uptake and transport of N sources in the AM symbiosis, the enzymatic activities of arginase and urease, and fungal gene expression in the extraradical and intraradical mycelium. We found that the C supply of the host plant triggers the uptake and transport of N in the symbiosis, and that the increase in N transport is orchestrated by changes in fungal gene expression. N transport in the symbiosis is stimulated only when the C is delivered by the host across the mycorrhizal interface, not when C is supplied directly to the fungal extraradical mycelium in the form of acetate. These findings support the importance of C flux from the root to the fungus as a key trigger for N uptake and transport and provide insight into the N transport regulation in the AM symbiosis. PMID- 22308427 TI - Cofilin under control of beta-arrestin-2 in NMDA-dependent dendritic spine plasticity, long-term depression (LTD), and learning. AB - Dendritic spines are dynamic, actin-rich structures that form the postsynaptic sites of most excitatory synapses in the brain. The F-actin severing protein cofilin has been implicated in the remodeling of dendritic spines and synapses under normal and pathological conditions, by yet unknown mechanisms. Here we report that beta-arrestin-2 plays an important role in NMDA-induced remodeling of dendritic spines and synapses via translocation of active cofilin to dendritic spines. NMDAR activation triggers cofilin activation through calcineurin and phosphatidylinositol 3-kinase (PI3K)-mediated dephosphorylation and promotes cofilin translocation to dendritic spines that is mediated by beta-arrestin-2. Hippocampal neurons lacking beta-arrestin-2 develop mature spines that fail to remodel in response to NMDA. beta-Arrestin-2-deficient mice exhibit normal hippocampal long-term potentiation, but significantly impaired NMDA-dependent long-term depression and spatial learning deficits. Moreover, beta-arrestin-2 deficient hippocampal neurons are resistant to Abeta-induced dendritic spine loss. Our studies demonstrate unique functions of beta-arrestin-2 in NMDAR mediated dendritic spine and synapse plasticity through spatial control over cofilin activation. PMID- 22308429 TI - Viruses do replicate in cell-free systems. PMID- 22308428 TI - Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa. AB - Hereditary retinal blindness is caused by mutations in genes expressed in photoreceptors or retinal pigment epithelium. Gene therapy in mouse and dog models of a primary retinal pigment epithelium disease has already been translated to human clinical trials with encouraging results. Treatment for common primary photoreceptor blindness, however, has not yet moved from proof of concept to the clinic. We evaluated gene augmentation therapy in two blinding canine photoreceptor diseases that model the common X-linked form of retinitis pigmentosa caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, which encodes a photoreceptor ciliary protein, and provide evidence that the therapy is effective. After subretinal injections of adeno-associated virus-2/5-vectored human RPGR with human IRBP or GRK1 promoters, in vivo imaging showed preserved photoreceptor nuclei and inner/outer segments that were limited to treated areas. Both rod and cone photoreceptor function were greater in treated (three of four) than in control eyes. Histopathology indicated normal photoreceptor structure and reversal of opsin mislocalization in treated areas expressing human RPGR protein in rods and cones. Postreceptoral remodeling was also corrected: there was reversal of bipolar cell dendrite retraction evident with bipolar cell markers and preservation of outer plexiform layer thickness. Efficacy of gene therapy in these large animal models of X-linked retinitis pigmentosa provides a path for translation to human treatment. PMID- 22308430 TI - Nonlinear Laplacian spectral analysis for time series with intermittency and low frequency variability. AB - Many processes in science and engineering develop multiscale temporal and spatial patterns, with complex underlying dynamics and time-dependent external forcings. Because of the importance in understanding and predicting these phenomena, extracting the salient modes of variability empirically from incomplete observations is a problem of wide contemporary interest. Here, we present a technique for analyzing high-dimensional, complex time series that exploits the geometrical relationships between the observed data points to recover features characteristic of strongly nonlinear dynamics (such as intermittency and rare events), which are not accessible to classical singular spectrum analysis. The method employs Laplacian eigenmaps, evaluated after suitable time-lagged embedding, to produce a reduced representation of the observed samples, where standard tools of matrix algebra can be used to perform truncated singular-value decomposition despite the nonlinear geometrical structure of the dataset. We illustrate the utility of the technique in capturing intermittent modes associated with the Kuroshio current in the North Pacific sector of a general circulation model and dimensional reduction of a low-order atmospheric model featuring chaotic intermittent regime transitions, where classical singular spectrum analysis is already known to fail dramatically. PMID- 22308432 TI - Percentage conservation targets are problematic for marine mammals. PMID- 22308431 TI - Antibody directs properdin-dependent activation of the complement alternative pathway in a mouse model of abdominal aortic aneurysm. AB - Abdominal aortic aneurysm (AAA) is a complex inflammatory vascular disease. There are currently limited treatment options for AAA when surgery is inapplicable. Therefore, insights into molecular mechanisms underlying AAA pathogenesis may reveal therapeutic targets that could be manipulated pharmacologically or biologically to halt disease progression. Using an elastase-induced AAA mouse model, we previously established that the complement alternative pathway (AP) plays a critical role in the development of AAA. However, the mechanism by which complement AP is initiated remains undefined. The complement protein properdin, traditionally viewed as a positive regulator of the AP, may also initiate complement activation by binding directly to target surfaces. In this study, we sought to determine whether properdin serves as a focal point for the initiation of the AP complement activation in AAA. Using a properdin loss of function mutation in mice and a mutant form of the complement factor B protein that produces a stable, properdin-free AP C3 convertase, we show that properdin is required for the development of elastase-induced AAA in its primary role as a convertase stabilizer. Unexpectedly, we find that, in AAA, natural IgG antibodies direct AP-mediated complement activation. The absence of IgG abrogates C3 deposition in elastase-perfused aortic wall and protects animals from AAA development. We also determine that blockade of properdin activity prevents aneurysm formation. These results indicate that an innate immune response to self antigens activates the complement system and initiates the inflammatory cascade in AAA. Moreover, the study suggests that properdin-targeting strategies may halt aneurysmal growth. PMID- 22308433 TI - Jumonji domain-containing protein 3 regulates histone 3 lysine 27 methylation during bovine preimplantation development. AB - Understanding the mechanisms of epigenetic remodeling that follow fertilization is a fundamental step toward understanding the bases of early embryonic development and pluripotency. Extensive and dynamic chromatin remodeling is observed after fertilization, including DNA methylation and histone modifications. These changes underlie the transition from gametic to embryonic chromatin and are thought to facilitate embryonic genome activation. In particular, trimethylation of histone 3 lysine 27 (H3K27me3) is associated with gene-specific transcription repression. Global levels of this epigenetic mark are high in oocyte chromatin and decrease to minimal levels at the time of embryonic genome activation. We provide evidence that the decrease in H3K27me3 observed during early development is cell-cycle independent, suggesting an active mechanism for removal of this epigenetic mark. Among H3K27me3-specific demethylases, Jumonji domain-containing protein 3 (JMJD3), but not ubiquitously transcribed tetratricopeptide repeat X (UTX), present high transcript levels in oocytes. Soon after fertilization JMJD3 protein levels increase, concurrent with a decrease in mRNA levels. This pattern of expression suggests maternal inheritance of JMJD3. Knockdown of JMJD3 by siRNA injection in parthenogenetically activated metaphase II oocytes resulted in inhibition of the H3K27me3 decrease normally observed in preimplantation embryos. Moreover, knockdown of JMJD3 in oocytes reduced the rate of blastocyst development. Overall, these results indicate that JMJD3 is involved in active demethylation of H3K27me3 during early embryo development and that this mark plays an important role during the progression of embryos to blastocysts. PMID- 22308434 TI - Ecotopic viral integration site 1 (EVI1) regulates multiple cellular processes important for cancer and is a synergistic partner for FOS protein in invasive tumors. AB - Ecotropic viral integration site 1 (EVI1) is an oncogenic dual domain zinc finger transcription factor that plays an essential role in the regulation of hematopoietic stem cell renewal, and its overexpression in myeloid leukemia and epithelial cancers is associated with poor patient survival. Despite the discovery of EVI1 in 1988 and its emerging role as a dominant oncogene in various types of cancer, few EVI1 target genes are known. This lack of knowledge has precluded a clear understanding of exactly how EVI1 contributes to cancer. Using a combination of ChIP-Seq and microarray studies in human ovarian carcinoma cells, we show that the two zinc finger domains of EVI1 bind to DNA independently and regulate different sets of target genes. Strikingly, an enriched fraction of EVI1 target genes are cancer genes or genes associated with cancer. We also show that more than 25% of EVI1-occupied genes contain linked EVI1 and activator protein (AP)1 DNA binding sites, and this finding provides evidence for a synergistic cooperative interaction between EVI1 and the AP1 family member FOS in the regulation of cell adhesion, proliferation, and colony formation. An increased number of dual EVI1/AP1 target genes are also differentially regulated in late-stage ovarian carcinomas, further confirming the importance of the functional cooperation between EVI1 and FOS. Collectively, our data indicate that EVI1 is a multipurpose transcription factor that synergizes with FOS in invasive tumors. PMID- 22308435 TI - Studies on Axenfeld-Rieger syndrome patients and mice reveal Foxc1's role in corneal neovascularization. PMID- 22308436 TI - Assembly of reconfigurable one-dimensional colloidal superlattices due to a synergy of fundamental nanoscale forces. AB - We report that triangular gold nanoprisms in the presence of attractive depletion forces and repulsive electrostatic forces assemble into equilibrium one dimensional lamellar crystals in solution with interparticle spacings greater than four times the thickness of the nanoprisms. Experimental and theoretical studies reveal that the anomalously large d spacings of the lamellar superlattices are due to a balance between depletion and electrostatic interactions, both of which arise from the surfactant cetyltrimethylammonium bromide. The effects of surfactant concentration, temperature, ionic strength of the solution, and prism edge length on the lattice parameters have been investigated and provide a variety of tools for in situ modulation of these colloidal superstructures. Additionally, we demonstrate a purification procedure based on our observations that can be used to efficiently separate triangular nanoprisms from spherical nanoparticles formed concomitantly during their synthesis. PMID- 22308437 TI - Exposure to anticancer drugs can result in transgenerational genomic instability in mice. AB - The genetic effects of human exposure to anticancer drugs remain poorly understood. To establish whether exposure to anticancer drugs can result not only in mutation induction in the germ line of treated animals, but also in altered mutation rates in their offspring, we evaluated mutation rates in the offspring of male mice treated with three commonly used chemotherapeutic agents: cyclophosphamide, mitomycin C, and procarbazine. The doses of paternal exposure were approximately equivalent to those used clinically. Using single-molecule PCR, the frequency of mutation at the mouse expanded simple tandem repeat locus Ms6-hm was established in DNA samples extracted from sperm and bone marrow of the offspring of treated males. After paternal exposure to any one of these three drugs, expanded simple tandem repeat mutation frequencies were significantly elevated in the germ line (sperm) and bone marrow of their offspring. This observed transgenerational instability was attributed to elevated mutation rates at the alleles derived from both the exposed fathers and from the nonexposed mothers, thus implying a genome-wide destabilization. Our results suggest that paternal exposure to a wide variety of mutagens can result in transgenerational instability manifesting in their offspring. Our data also raise important issues concerning delayed transgenerational effects in the children of survivors of anticancer therapy. PMID- 22308438 TI - Subunit order of eukaryotic TRiC/CCT chaperonin by cross-linking, mass spectrometry, and combinatorial homology modeling. AB - The TRiC/CCT chaperonin is a 1-MDa hetero-oligomer of 16 subunits that assists the folding of proteins in eukaryotes. Low-resolution structural studies confirmed the TRiC particle to be composed of two stacked octameric rings enclosing a folding cavity. The exact arrangement of the different proteins in the rings underlies the functionality of TRiC and is likely to be conserved across all eukaryotes. Yet despite its importance it has not been determined conclusively, mainly because the different subunits appear nearly identical under low resolution. This work successfully addresses the arrangement problem by the emerging technique of cross-linking, mass spectrometry, and modeling. We cross linked TRiC under native conditions with a cross-linker that is primarily reactive toward exposed lysine side chains that are spatially close in the context of the particle. Following digestion and mass spectrometry we were able to identify over 60 lysine pairs that underwent cross-linking, thus providing distance restraints between specific residues in the complex. Independently of the cross-link set, we constructed 40,320 (= 8 factorial) computational models of the TRiC particle, which exhaustively enumerate all the possible arrangements of the different subunits. When we assessed the compatibility of each model with the cross-link set, we discovered that one specific model is significantly more compatible than any other model. Furthermore, bootstrapping analysis confirmed that this model is 10 times more likely to result from this cross-link set than the next best-fitting model. Our subunit arrangement is very different than any of the previously reported models and changes the context of existing and future findings on TRiC. PMID- 22308439 TI - Coherent angular motion in the establishment of multicellular architecture of glandular tissues. AB - Glandular tissues form ducts (tubes) and acini (spheres) in multicellular organisms. This process is best demonstrated in the organization of the ductal tree of the mammary gland and in 3D models of morphogenesis in culture. Here, we asked a fundamental question: How do single adult epithelial cells generate polarized acini when placed in a surrogate basement membrane 3D gel? Using human breast epithelial cells from either reduction mammoplasty or nonmalignant breast cell lines, we observed a unique cellular movement where single cells undergo multiple rotations and then maintain it cohesively as they divide to assemble into acini. This coherent angular motion (CAMo) was observed in both primary cells and breast cell lines. If CAMo was disrupted, the final geometry was not a sphere. The malignant counterparts of the human breast cell lines in 3D were randomly motile, did not display CAMo, and did not form spheres. Upon "phenotypic reversion" of malignant cells, both CAMo and spherical architecture were restored. We show that cell-cell adhesion and tissue polarity are essential for the formation of acini and link the functional relevance of CAMo to the establishment of spherical architecture rather than to multicellular aggregation or growth. We propose that CAMo is an integral step in the formation of the tissue architecture and that its disruption is involved in malignant transformation. PMID- 22308440 TI - Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. AB - Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about how they work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normal waking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen level-dependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition. PMID- 22308441 TI - Regulation of inositol 1,3,4-trisphosphate 5/6-kinase (ITPK1) by reversible lysine acetylation. AB - The enzyme inositol 1,3,4-trisphosphate 5/6-kinase (ITPK1) catalyzes the rate limiting step in the formation of higher phosphorylated forms of inositol in mammalian cells. Because it sits at a key regulatory point in the inositol metabolic pathway, its activity is likely to be regulated. We have previously shown that ITPK1 is phosphorylated, a posttranslational modification used by cells to regulate enzyme activity. We show here that ITPK1 is modified by acetylation of internal lysine residues. The acetylation sites, as determined by mass spectrometry, were found to be lysines 340, 383, and 410, which are all located on the surface of this protein. Overexpression of the acetyltransferases CREB-binding protein or p300 resulted in the acetylation of ITPK1, whereas overexpression of mammalian silent information regulator 2 resulted in the deacetylation of ITPK1. Functionally, ITPK1 acetylation regulates its stability. CREB-binding protein dramatically decreased the half-life of ITPK1. We further found that ITPK1 acetylation down-regulated its enzyme activity. HEK293 cells stably expressing acetylated ITPK1 had reduced levels of the higher phosphorylated forms of inositol, compared with the levels seen in cells expressing unacetylated ITPK1. These results demonstrate that lysine acetylation alters both the stability as well as the activity of ITPK1 in cells. PMID- 22308442 TI - Uranyl peroxide enhanced nuclear fuel corrosion in seawater. AB - The Fukushima-Daiichi nuclear accident brought together compromised irradiated fuel and large amounts of seawater in a high radiation field. Based on newly acquired thermochemical data for a series of uranyl peroxide compounds containing charge-balancing alkali cations, here we show that nanoscale cage clusters containing as many as 60 uranyl ions, bonded through peroxide and hydroxide bridges, are likely to form in solution or as precipitates under such conditions. These species will enhance the corrosion of the damaged fuel and, being thermodynamically stable and kinetically persistent in the absence of peroxide, they can potentially transport uranium over long distances. PMID- 22308443 TI - Extreme anti-oxidant protection against ionizing radiation in bdelloid rotifers. AB - Bdelloid rotifers, a class of freshwater invertebrates, are extraordinarily resistant to ionizing radiation (IR). Their radioresistance is not caused by reduced susceptibility to DNA double-strand breakage for IR makes double-strand breaks (DSBs) in bdelloids with essentially the same efficiency as in other species, regardless of radiosensitivity. Instead, we find that the bdelloid Adineta vaga is far more resistant to IR-induced protein carbonylation than is the much more radiosensitive nematode Caenorhabditis elegans. In both species, the dose-response for protein carbonylation parallels that for fecundity reduction, manifested as embryonic death. We conclude that the great radioresistance of bdelloid rotifers is a consequence of an unusually effective system of anti-oxidant protection of cellular constituents, including those required for DSB repair, allowing bdelloids to recover and continue reproducing after doses of IR causing hundreds of DSBs per nucleus. Bdelloid rotifers therefore offer an advantageous system for investigation of enhanced anti-oxidant protection and its consequences in animal systems. PMID- 22308444 TI - Nonequilibrium atmospheric secondary organic aerosol formation and growth. AB - Airborne particles play critical roles in air quality, health effects, visibility, and climate. Secondary organic aerosols (SOA) formed from oxidation of organic gases such as alpha-pinene account for a significant portion of total airborne particle mass. Current atmospheric models typically incorporate the assumption that SOA mass is a liquid into which semivolatile organic compounds undergo instantaneous equilibrium partitioning to grow the particles into the size range important for light scattering and cloud condensation nuclei activity. We report studies of particles from the oxidation of alpha-pinene by ozone and NO(3) radicals at room temperature. SOA is primarily formed from low-volatility ozonolysis products, with a small contribution from higher volatility organic nitrates from the NO(3) reaction. Contrary to expectations, the particulate nitrate concentration is not consistent with equilibrium partitioning between the gas phase and a liquid particle. Rather the fraction of organic nitrates in the particles is only explained by irreversible, kinetically determined uptake of the nitrates on existing particles, with an uptake coefficient that is 1.6% of that for the ozonolysis products. If the nonequilibrium particle formation and growth observed in this atmospherically important system is a general phenomenon in the atmosphere, aerosol models may need to be reformulated. The reformulation of aerosol models could impact the predicted evolution of SOA in the atmosphere both outdoors and indoors, its role in heterogeneous chemistry, its projected impacts on air quality, visibility, and climate, and hence the development of reliable control strategies. PMID- 22308445 TI - Modeling and design by hierarchical natural moves. AB - We develop a unique algorithm implemented in the program MOSAICS (Methodologies for Optimization and Sampling in Computational Studies) that is capable of nanoscale modeling without compromising the resolution of interest. This is achieved by modeling with customizable hierarchical degrees of freedom, thereby circumventing major limitations of conventional molecular modeling. With the emergence of RNA-based nanotechnology, large RNAs in all-atom representation are used here to benchmark our algorithm. Our method locates all favorable structural states of a model RNA of significant complexity while improving sampling accuracy and increasing speed many fold over existing all-atom RNA modeling methods. We also modeled the effects of sequence mutations on the structural building blocks of tRNA-based nanotechnology. With its flexibility in choosing arbitrary degrees of freedom as well as in allowing different all-atom energy functions, MOSAICS is an ideal tool to model and design biomolecules of the nanoscale. PMID- 22308446 TI - Predicting DNA-mediated colloidal pair interactions. PMID- 22308447 TI - DNA charge transport as a first step in coordinating the detection of lesions by repair proteins. AB - Damaged bases in DNA are known to lead to errors in replication and transcription, compromising the integrity of the genome. We have proposed a model where repair proteins containing redox-active [4Fe-4S] clusters utilize DNA charge transport (CT) as a first step in finding lesions. In this model, the population of sites to search is reduced by a localization of protein in the vicinity of lesions. Here, we examine this model using single-molecule atomic force microscopy (AFM). XPD, a 5'-3' helicase involved in nucleotide excision repair, contains a [4Fe-4S] cluster and exhibits a DNA-bound redox potential that is physiologically relevant. In AFM studies, we observe the redistribution of XPD onto kilobase DNA strands containing a single base mismatch, which is not a specific substrate for XPD but, like a lesion, inhibits CT. We further provide evidence for DNA-mediated signaling between XPD and Endonuclease III (EndoIII), a base excision repair glycosylase that also contains a [4Fe-4S] cluster. When XPD and EndoIII are mixed together, they coordinate in relocalizing onto the mismatched strand. However, when a CT-deficient mutant of either repair protein is combined with the CT-proficient repair partner, no relocalization occurs. These data not only indicate a general link between the ability of a repair protein to carry out DNA CT and its ability to redistribute onto DNA strands near lesions but also provide evidence for coordinated DNA CT between different repair proteins in their search for damage in the genome. PMID- 22308448 TI - Enabling high-temperature nanophotonics for energy applications. AB - The nascent field of high-temperature nanophotonics could potentially enable many important solid-state energy conversion applications, such as thermophotovoltaic energy generation, selective solar absorption, and selective emission of light. However, special challenges arise when trying to design nanophotonic materials with precisely tailored optical properties that can operate at high-temperatures (> 1,100 K). These include proper material selection and purity to prevent melting, evaporation, or chemical reactions; severe minimization of any material interfaces to prevent thermomechanical problems such as delamination; robust performance in the presence of surface diffusion; and long-range geometric precision over large areas with severe minimization of very small feature sizes to maintain structural stability. Here we report an approach for high-temperature nanophotonics that surmounts all of these difficulties. It consists of an analytical and computationally guided design involving high-purity tungsten in a precisely fabricated photonic crystal slab geometry (specifically chosen to eliminate interfaces arising from layer-by-layer fabrication) optimized for high performance and robustness in the presence of roughness, fabrication errors, and surface diffusion. It offers near-ultimate short-wavelength emittance and low, ultra-broadband long-wavelength emittance, along with a sharp cutoff offering 41 emittance contrast over 10% wavelength separation. This is achieved via Q matching, whereby the absorptive and radiative rates of the photonic crystal's cavity resonances are matched. Strong angular emission selectivity is also observed, with short-wavelength emission suppressed by 50% at 75 degrees compared to normal incidence. Finally, a precise high-temperature measurement technique is developed to confirm that emission at 1,225 K can be primarily confined to wavelengths shorter than the cutoff wavelength. PMID- 22308449 TI - The diverse effects of mechanical loading on active hair bundles. AB - Hair cells in the auditory, vestibular, and lateral-line systems of vertebrates receive inputs through a remarkable variety of accessory structures that impose complex mechanical loads on the mechanoreceptive hair bundles. Although the physiological and morphological properties of the hair bundles in each organ are specialized for detecting the relevant inputs, we propose that the mechanical load on the bundles also adjusts their responsiveness to external signals. We use a parsimonious description of active hair-bundle motility to show how the mechanical environment can regulate a bundle's innate behavior and response to input. We find that an unloaded hair bundle can behave very differently from one subjected to a mechanical load. Depending on how it is loaded, a hair bundle can function as a switch, active oscillator, quiescent resonator, or low-pass filter. Moreover, a bundle displays a sharply tuned, nonlinear, and sensitive response for some loading conditions and an untuned or weakly tuned, linear, and insensitive response under other circumstances. Our simple characterization of active hair-bundle motility explains qualitatively most of the observed features of bundle motion from different organs and organisms. The predictions stemming from this description provide insight into the operation of hair bundles in a variety of contexts. PMID- 22308450 TI - Predictable and efficient carbon sequestration in the North Pacific Ocean supported by symbiotic nitrogen fixation. AB - The atmospheric and deep sea reservoirs of carbon dioxide are linked via physical, chemical, and biological processes. The last of these include photosynthesis, particle settling, and organic matter remineralization, and are collectively termed the "biological carbon pump." Herein, we present results from a 13-y (1992-2004) sediment trap experiment conducted in the permanently oligotrophic North Pacific Subtropical Gyre that document a large, rapid, and predictable summertime (July 15-August 15) pulse in particulate matter export to the deep sea (4,000 m). Peak daily fluxes of particulate matter during the summer export pulse (SEP) average 408, 283, 24.1, 1.1, and 67.5 MUmol.m(-2).d(-1) for total carbon, organic carbon, nitrogen, phosphorus (PP), and biogenic silica, respectively. The SEP is approximately threefold greater than mean wintertime particle fluxes and fuels more efficient carbon sequestration because of low remineralization during downward transit that leads to elevated total carbon/PP and organic carbon/PP particle stoichiometry (371:1 and 250:1, respectively). Our long-term observations suggest that seasonal changes in the microbial assemblage, namely, summertime increases in the biomass and productivity of symbiotic nitrogen-fixing cyanobacteria in association with diatoms, are the main cause of the prominent SEP. The recurrent SEP is enigmatic because it is focused in time despite the absence of any obvious predictable stimulus or habitat condition. We hypothesize that changes in day length (photoperiodism) may be an important environmental cue to initiate aggregation and subsequent export of organic matter to the deep sea. PMID- 22308451 TI - Tumor suppressor function of Liver kinase B1 (Lkb1) is linked to regulation of epithelial integrity. AB - Although loss of epithelial integrity is a hallmark of advanced cancer, it remains poorly understood whether genetic alterations corrupting this integrity causally facilitate tumorigenesis. We show that conditional deletion of tumor suppressor gene Lkb1 (Par-4) in the mammary gland compromises epithelial integrity manifested by mislocalization of cell polarity markers, lateralization of tight junctions, deterioration of desmosomes and basement membrane (BM), and hyperbranching of the mammary ductal tree. We identify the desmosomal BM remodelling serine protease Hepsin as a key factor mediating Lkb1 loss-induced structural alterations in mammary epithelium and BM fragmentation. Although loss of Lkb1 alone does not promote mammary tumorigenesis, combination of Lkb1 deficiency with oncogenic c-Myc leads to dramatic acceleration in tumor formation. The results coupling Lkb1 loss-mediated epithelial integrity defects to mislocalization of serine protease Hepsin and to oncogenic synergy with c-Myc imply that Lkb1 loss facilitates oncogenic proliferation by releasing epithelial cells from structural BM boundaries. PMID- 22308452 TI - Yet another role for natural killer cells: cytotoxicity in immune regulation and viral persistence. PMID- 22308453 TI - Functional characterization of the guanine nucleotide exchange factor (GEF) motif of GIV protein reveals a threshold effect in signaling. AB - Heterotrimeric G proteins are critical signal-transducing molecules controlled by a complex network of regulators. GIV (a.k.a. Girdin) is a unique component of this network and a nonreceptor guanine nucleotide exchange factor (GEF) that functions via a signature motif. GIV's GEF motif is involved in the regulation of critical biological processes such as phosphoinositide 3 kinase (PI3K)-Akt signaling, actin cytoskeleton remodeling, cell migration, and cancer metastasis. Here we investigated how the GEF function of GIV affects the wiring of its signaling pathway to shape different biological responses. Using a structure guided approach, we designed a battery of GIV mutants with different Galphai binding and -activating properties and used it to dissect the specific impact of changes in GIV's GEF activity on several cellular responses. In vivo signaling assays revealed a threshold effect of GEF activity for the activation of Akt by GIV in different cell lines and by different stimuli. Akt signaling is minimal at low GEF activity and is sharply increased to reach a maximum above a threshold of GEF activity, suggesting that GIV is a critical signal amplifier and that activation of Akt is ultrasensitive to changes in GIV's GEF activity. A similar threshold dependence was observed for other biological functions promoted by GIV such as remodeling of the actin cytoskeleton and cell migration. This functional characterization of GIV's GEF motif provides insights into the molecular interactions between nonreceptor GEFs and G proteins and the mechanisms that govern this signal transduction pathway. PMID- 22308454 TI - Genome-wide siRNA screen for mediators of NF-kappaB activation. AB - Although canonical NFkappaB is frequently critical for cell proliferation, survival, or differentiation, NFkappaB hyperactivation can cause malignant, inflammatory, or autoimmune disorders. Despite intensive study, mammalian NFkappaB pathway loss-of-function RNAi analyses have been limited to specific protein classes. We therefore undertook a human genome-wide siRNA screen for novel NFkappaB activation pathway components. Using an Epstein Barr virus latent membrane protein (LMP1) mutant, the transcriptional effects of which are canonical NFkappaB-dependent, we identified 155 proteins significantly and substantially important for NFkappaB activation in HEK293 cells. These proteins included many kinases, phosphatases, ubiquitin ligases, and deubiquinating enzymes not previously known to be important for NFkappaB activation. Relevance to other canonical NFkappaB pathways was extended by finding that 118 of the 155 LMP1 NF-kappaB activation pathway components were similarly important for IL 1beta-, and 79 for TNFalpha-mediated NFkappaB activation in the same cells. MAP3K8, PIM3, and six other enzymes were uniquely relevant to LMP1-mediated NFkappaB activation. Most novel pathway components functioned upstream of IkappaB kinase complex (IKK) activation. Robust siRNA knockdown effects were confirmed for all mRNAs or proteins tested. Although multiple ZC3H-family proteins negatively regulate NFkappaB, ZC3H13 and ZC3H18 were activation pathway components. ZC3H13 was critical for LMP1, TNFalpha, and IL-1beta NFkappaB dependent transcription, but not for IKK activation, whereas ZC3H18 was critical for IKK activation. Down-modulators of LMP1 mediated NFkappaB activation were also identified. These experiments identify multiple targets to inhibit or stimulate LMP1-, IL-1beta-, or TNFalpha-mediated canonical NFkappaB activation. PMID- 22308455 TI - Three differentiation states risk-stratify bladder cancer into distinct subtypes. AB - Current clinical judgment in bladder cancer (BC) relies primarily on pathological stage and grade. We investigated whether a molecular classification of tumor cell differentiation, based on a developmental biology approach, can provide additional prognostic information. Exploiting large preexisting gene-expression databases, we developed a biologically supervised computational model to predict markers that correspond with BC differentiation. To provide mechanistic insight, we assessed relative tumorigenicity and differentiation potential via xenotransplantation. We then correlated the prognostic utility of the identified markers to outcomes within gene expression and formalin-fixed paraffin-embedded (FFPE) tissue datasets. Our data indicate that BC can be subclassified into three subtypes, on the basis of their differentiation states: basal, intermediate, and differentiated, where only the most primitive tumor cell subpopulation within each subtype is capable of generating xenograft tumors and recapitulating downstream populations. We found that keratin 14 (KRT14) marks the most primitive differentiation state that precedes KRT5 and KRT20 expression. Furthermore, KRT14 expression is consistently associated with worse prognosis in both univariate and multivariate analyses. We identify here three distinct BC subtypes on the basis of their differentiation states, each harboring a unique tumor-initiating population. PMID- 22308456 TI - "Evolution Canyon," a potential microscale monitor of global warming across life. AB - Climatic change and stress is a major driving force of evolution. The effects of climate change on living organisms have been shown primarily on regional and global scales. Here I propose the "Evolution Canyon" (EC) microscale model as a potential life monitor of global warming in Israel and the rest of the world. The EC model reveals evolution in action at a microscale involving biodiversity divergence, adaptation, and incipient sympatric speciation across life from viruses and bacteria through fungi, plants, and animals. The EC consists of two abutting slopes separated, on average, by 200 m. The tropical, xeric, savannoid, "African" south-facing slope (AS = SFS) abuts the forested "European" north facing slope (ES = NFS). The AS receives 200-800% higher solar radiation than the ES. The ES represents the south European forested maquis. The AS and ES exhibit drought and shade stress, respectively. Major adaptations on the AS are because of solar radiation, heat, and drought, whereas those on the ES relate to light stress and photosynthesis. Preliminary evidence suggests the extinction of some European species on the ES and AS. In Drosophila, a 10-fold higher migration was recorded in 2003 from the AS to ES. I advance some predictions that could be followed in diverse species in EC. The EC microclimatic model is optimal to track global warming at a microscale across life from viruses and bacteria to mammals in Israel, and in additional ECs across the planet. PMID- 22308457 TI - Inhibiting platelet-stimulated blood coagulation by inhibition of mitochondrial respiration. AB - Platelets are important mediators of blood coagulation that lack nuclei, but contain mitochondria. Although the presence of mitochondria in platelets has long been recognized, platelet mitochondrial function remains largely unaddressed. On the basis of a small amount of literature that suggests platelet mitochondria are functional, we hypothesized that the inhibition of platelet mitochondria disrupts platelet function and platelet-activated blood coagulation. To test this hypothesis, members of the tetrazole, thiazole, and 1,2,3-triazole families of small molecule heterocycles were screened for the ability to inhibit isolated mitochondrial respiration and coagulation of whole blood. The families of heterocycles screened were chosen on the basis of the ability of the heterocycle family to inhibit a biomimetic model of cytochrome c oxidase (CcO). The strength of mitochondrial inhibition correlates with each compound's ability to deter platelet stimulation and platelet-activated blood clotting. These results suggest that for this class of molecules, inhibition of blood coagulation may be occurring through a mechanism involving mitochondrial inhibition. PMID- 22308458 TI - Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires. AB - Fluorescence imaging is an attractive method for monitoring neuronal activity. A key challenge for optically monitoring voltage is development of sensors that can give large and fast responses to changes in transmembrane potential. We now present fluorescent sensors that detect voltage changes in neurons by modulation of photo-induced electron transfer (PeT) from an electron donor through a synthetic molecular wire to a fluorophore. These dyes give bigger responses to voltage than electrochromic dyes, yet have much faster kinetics and much less added capacitance than existing sensors based on hydrophobic anions or voltage sensitive ion channels. These features enable single-trial detection of synaptic and action potentials in cultured hippocampal neurons and intact leech ganglia. Voltage-dependent PeT should be amenable to much further optimization, but the existing probes are already valuable indicators of neuronal activity. PMID- 22308459 TI - Human ovarian cancer stem/progenitor cells are stimulated by doxorubicin but inhibited by Mullerian inhibiting substance. AB - Women with late-stage ovarian cancer usually develop chemotherapeutic-resistant recurrence. It has been theorized that a rare cancer stem cell, which is responsible for the growth and maintenance of the tumor, is also resistant to conventional chemotherapeutics. We have isolated from multiple ovarian cancer cell lines an ovarian cancer stem cell-enriched population marked by CD44, CD24, and Epcam (3+) and by negative selection for Ecadherin (Ecad-) that comprises less than 1% of cancer cells and has increased colony formation and shorter tumor free intervals in vivo after limiting dilution. Surprisingly, these cells are not only resistant to chemotherapeutics such as doxorubicin, but also are stimulated by it, as evidenced by the significantly increased number of colonies in treated 3+Ecad- cells. Similarly, proliferation of the 3+Ecad- cells in monolayer increased with treatment, by either doxorubicin or cisplatin, compared with the unseparated or cancer stem cell-depleted 3-Ecad+ cells. However, these cells are sensitive to Mullerian inhibiting substance (MIS), which decreased colony formation. MIS inhibits ovarian cancer cells by inducing G1 arrest of the 3+Ecad- subpopulation through the induction of cyclin-dependent kinase inhibitors. 3+Ecad cells selectively expressed LIN28, which colocalized by immunofluorescence with the 3+ cancer stem cell markers in the human ovarian carcinoma cell line, OVCAR 5, and is also highly expressed in transgenic murine models of ovarian cancer and in other human ovarian cancer cell lines. These results suggest that chemotherapeutics may be stimulative to cancer stem cells and that selective inhibition of these cells by treating with MIS or targeting LIN28 should be considered in the development of therapeutics. PMID- 22308460 TI - Monoallelic silencing and haploinsufficiency in early murine intestinal neoplasms. AB - Studies of tumors from human familial adenomatous polyposis, sporadic colon cancer, and mouse and rat models of intestinal cancer indicate that the majority of early adenomas develop through loss of normal function of the Adenomatous polyposis coli (APC) gene. In murine models of familial adenomatous polyposis, specifically the multiple intestinal neoplasia mouse (Min) and the polyposis in the rat colon (Pirc) rat, most adenomas have lost their WT copy of the Apc gene through loss of heterozygosity by homologous somatic recombination. We report that large colonic adenomas in the Pirc rat have no detectable copy number losses or gains in genomic material and that most tumors lose heterozygosity only on the short arm of chromosome 18. Examination of early mouse and rat tumors indicates that a substantial subset of tumors shows maintenance of heterozygosity of Apc in genomic DNA, apparently violating Knudson's two-hit hypothesis. Sequencing of the Apc gene in a sampling of rat tumors failed to find secondary mutations in the majority of tumors that maintained heterozygosity of Apc in genomic DNA. Using quantitative allele-specific assays of Apc cDNA, we discovered two neoplastic pathways. One class of tumors maintains heterozygosity of Apc(Min/+) or Apc(Pirc/+) RNA expression and may involve haploinsufficiency for Apc function. Another class of tumors exhibits highly biased monoallelic expression of the mutant Apc allele, providing evidence for a stochastic or random process of monoallelic epigenetic silencing of the tumor suppressor gene Apc. PMID- 22308461 TI - The maximum rate of mammal evolution. AB - How fast can a mammal evolve from the size of a mouse to the size of an elephant? Achieving such a large transformation calls for major biological reorganization. Thus, the speed at which this occurs has important implications for extensive faunal changes, including adaptive radiations and recovery from mass extinctions. To quantify the pace of large-scale evolution we developed a metric, clade maximum rate, which represents the maximum evolutionary rate of a trait within a clade. We applied this metric to body mass evolution in mammals over the last 70 million years, during which multiple large evolutionary transitions occurred in oceans and on continents and islands. Our computations suggest that it took a minimum of 1.6, 5.1, and 10 million generations for terrestrial mammal mass to increase 100-, and 1,000-, and 5,000-fold, respectively. Values for whales were down to half the length (i.e., 1.1, 3, and 5 million generations), perhaps due to the reduced mechanical constraints of living in an aquatic environment. When differences in generation time are considered, we find an exponential increase in maximum mammal body mass during the 35 million years following the Cretaceous Paleogene (K-Pg) extinction event. Our results also indicate a basic asymmetry in macroevolution: very large decreases (such as extreme insular dwarfism) can happen at more than 10 times the rate of increases. Our findings allow more rigorous comparisons of microevolutionary and macroevolutionary patterns and processes. PMID- 22308462 TI - Nonimmunoglobulin target loci of activation-induced cytidine deaminase (AID) share unique features with immunoglobulin genes. AB - Activation-induced cytidine deaminase (AID) is required for both somatic hypermutation and class-switch recombination in activated B cells. AID is also known to target nonimmunoglobulin genes and introduce mutations or chromosomal translocations, eventually causing tumors. To identify as-yet-unknown AID targets, we screened early AID-induced DNA breaks by using two independent genome wide approaches. Along with known AID targets, this screen identified a set of unique genes (SNHG3, MALAT1, BCL7A, and CUX1) and confirmed that these loci accumulated mutations as frequently as Ig locus after AID activation. Moreover, these genes share three important characteristics with the Ig gene: translocations in tumors, repetitive sequences, and the epigenetic modification of chromatin by H3K4 trimethylation in the vicinity of cleavage sites. PMID- 22308463 TI - Lipid targeting domain with dual-membrane specificity that expands the diversity of intracellular targeting reactions. PMID- 22308464 TI - Negative and competitive social interactions are related to heightened proinflammatory cytokine activity. AB - Research has consistently documented that social relationships influence physical health, a link that may implicate systemic inflammation. We examined whether daily social interactions predict levels of proinflammatory cytokines IL-6 and the soluble receptor for tumor necrosis factor-alpha (sTNFalphaRII) and their reactivity to a social stressor. One-hundred twenty-two healthy young adults completed daily diaries for 8 d that assessed positive, negative, and competitive social interactions. Participants then engaged in laboratory stress challenges, and IL-6 and sTNFalphaRII were collected at baseline and at 25- and 80-min poststressor, from oral mucosal transudate. Negative social interactions predicted elevated sTNFalphaRII at baseline, and IL-6 and sTNFalphaRII 25-min poststressor, as well as total output of sTNFalphaRII. Competitive social interactions predicted elevated baseline levels of IL-6 and sTNFalphaRII and total output of both cytokines. These findings suggest that daily social interactions that are negative and competitive are associated prospectively with heightened proinflammatory cytokine activity. PMID- 22308465 TI - Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cells. AB - We recently showed that defined sets of transcription factors are sufficient to convert mouse and human fibroblasts directly into cells resembling functional neurons, referred to as "induced neuronal" (iN) cells. For some applications however, it would be desirable to convert fibroblasts into proliferative neural precursor cells (NPCs) instead of neurons. We hypothesized that NPC-like cells may be induced using the same principal approach used for generating iN cells. Toward this goal, we infected mouse embryonic fibroblasts derived from Sox2-EGFP mice with a set of 11 transcription factors highly expressed in NPCs. Twenty-four days after transgene induction, Sox2-EGFP(+) colonies emerged that expressed NPC specific genes and differentiated into neuronal and astrocytic cells. Using stepwise elimination, we found that Sox2 and FoxG1 are capable of generating clonal self-renewing, bipotent induced NPCs that gave rise to astrocytes and functional neurons. When we added the Pou and Homeobox domain-containing transcription factor Brn2 to Sox2 and FoxG1, we were able to induce tripotent NPCs that could be differentiated not only into neurons and astrocytes but also into oligodendrocytes. The transcription factors FoxG1 and Brn2 alone also were capable of inducing NPC-like cells; however, these cells generated less mature neurons, although they did produce astrocytes and even oligodendrocytes capable of integration into dysmyelinated Shiverer brain. Our data demonstrate that direct lineage reprogramming using target cell-type-specific transcription factors can be used to induce NPC-like cells that potentially could be used for autologous cell transplantation-based therapies in the brain or spinal cord. PMID- 22308466 TI - Maternal modulation of novelty effects on physical development. AB - Familiarity to the mother and the novelty afforded by the postnatal environment are two contrasting sources of neonatal influence. One hypothesis regarding their relationship is the maternal modulation hypothesis, which predicts that the same neonatal stimulation may have different effects depending on the maternal context. Here we tested this hypothesis using physical development, indexed by body weight, as an endpoint and found that, among offspring of mothers with a high initial swim-stress-induced corticosterone (CORT) response, neonatal novelty exposure induced an enhancement in early growth, and among offspring with mothers of a low initial CORT response, the same neonatal stimulation induced an impairment. At an older age, a novelty-induced increase in body weight was also found among offspring of mothers with high postnatal care reliability and a novelty-induced reduction found among offspring of mothers with low care reliability. These results support a maternal modulation of early stimulation effects on physical development and demonstrate that the maternal influence originates from multiple instead of any singular sources. These results (i) significantly extend the findings of maternal modulation from the domain of cognitive development to the domain of physical development; (ii) offer a unifying explanation for a previously inconsistent literature regarding early stimulation effects on body weight; and (iii) highlight the notion that the early experience effect involves no causal primacy but higher order interactions among the initial triggering events and subsequent events involving a multitude of maternal and nonmaternal influences. PMID- 22308467 TI - Agonist of growth hormone-releasing hormone reduces pneumolysin-induced pulmonary permeability edema. AB - Aggressive treatment with antibiotics in patients infected with Streptococcus pneumoniae induces release of the bacterial virulence factor pneumolysin (PLY). Days after lungs are sterile, this pore-forming toxin can still induce pulmonary permeability edema in patients, characterized by alveolar/capillary barrier dysfunction and impaired alveolar liquid clearance (ALC). ALC is mainly regulated through Na(+) transport by the apically expressed epithelial sodium channel (ENaC) and the basolaterally expressed Na(+)/K(+)-ATPase in type II alveolar epithelial cells. Because no standard treatment is currently available to treat permeability edema, the search for novel therapeutic candidates is of high priority. We detected mRNA expression for the active receptor splice variant SV1 of the hypothalamic polypeptide growth hormone-releasing hormone (GHRH), as well as for GHRH itself, in human lung microvascular endothelial cells (HL-MVEC). Therefore, we have evaluated the effect of the GHRH agonist JI-34 on PLY-induced barrier and ALC dysfunction. JI-34 blunts PLY-mediated endothelial hyperpermeability in monolayers of HL-MVEC, in a cAMP-dependent manner, by means of reducing the phosphorylation of myosin light chain and vascular endothelial (VE)-cadherin. In human airway epithelial H441 cells, PLY significantly impairs Na(+) uptake, but JI-34 restores it to basal levels by means of increasing cAMP levels. Intratracheal instillation of PLY into C57BL6 mice causes pulmonary alveolar epithelial and endothelial hyperpermeability as well as edema formation, all of which are blunted by JI-34. These findings point toward a protective role of the GHRH signaling pathway in PLY-induced permeability edema. PMID- 22308468 TI - Evidence for social working memory from a parametric functional MRI study. AB - Keeping track of various amounts of social cognitive information, including people's mental states, traits, and relationships, is fundamental to navigating social interactions. However, to date, no research has examined which brain regions support variable amounts of social information processing ("social load"). We developed a social working memory paradigm to examine the brain networks sensitive to social load. Two networks showed linear increases in activation as a function of increasing social load: the medial frontoparietal regions implicated in social cognition and the lateral frontoparietal system implicated in nonsocial forms of working memory. Of these networks, only load dependent medial frontoparietal activity was associated with individual differences in social cognitive ability (trait perspective-taking). Although past studies of nonsocial load have uniformly found medial frontoparietal activity decreases with increasing task demands, the current study demonstrates these regions do support increasing mental effort when such effort engages social cognition. Implications for the etiology of clinical disorders that implicate social functioning and potential interventions are discussed. PMID- 22308469 TI - Asynchronous Ca2+ current conducted by voltage-gated Ca2+ (CaV)-2.1 and CaV2.2 channels and its implications for asynchronous neurotransmitter release. AB - We have identified an asynchronously activated Ca(2+) current through voltage gated Ca(2+) (Ca(V))-2.1 and Ca(V)2.2 channels, which conduct P/Q- and N-type Ca(2+) currents that initiate neurotransmitter release. In nonneuronal cells expressing Ca(V)2.1 or Ca(V)2.2 channels and in hippocampal neurons, prolonged Ca(2+) entry activates a Ca(2+) current, I(Async), which is observed on repolarization and decays slowly with a half-time of 150-300 ms. I(Async) is not observed after L-type Ca(2+) currents of similar size conducted by Ca(V)1.2 channels. I(Async) is Ca(2+)-selective, and it is unaffected by changes in Na(+), K(+), Cl(-), or H(+) or by inhibitors of a broad range of ion channels. During trains of repetitive depolarizations, I(Async) increases in a pulse-wise manner, providing Ca(2+) entry that persists between depolarizations. In single-cultured hippocampal neurons, trains of depolarizations evoke excitatory postsynaptic currents that show facilitation followed by depression accompanied by asynchronous postsynaptic currents that increase steadily during the train in parallel with I(Async). I(Async) is much larger for slowly inactivating Ca(V)2.1 channels containing beta(2a)-subunits than for rapidly inactivating channels containing beta(1b)-subunits. I(Async) requires global rises in intracellular Ca(2+), because it is blocked when Ca(2+) is chelated by 10 mM EGTA in the patch pipette. Neither mutations that prevent Ca(2+) binding to calmodulin nor mutations that prevent calmodulin regulation of Ca(V)2.1 block I(Async). The rise of I(Async) during trains of stimuli, its decay after repolarization, its dependence on global increases of Ca(2+), and its enhancement by beta(2a) subunits all resemble asynchronous release, suggesting that I(Async) is a Ca(2+) source for asynchronous neurotransmission. PMID- 22308470 TI - Reentrant spiral waves of spreading depression cause macular degeneration in hypoglycemic chicken retina. AB - Spreading depression (SD), a slow diffusion-mediated self-sustained wave of depolarization that severely disrupts neuronal function, has been implicated as a cause of cellular injury in a number of central nervous system pathologies, including blind spots in the retina. Here we show that in the hypoglycemic chicken retina, spontaneous episodes of SD can occur, resulting in irreversible punctate lesions in the macula, the region of highest visual acuity in the central region of the retina. These lesions in turn can act as sites of origin for secondary self-sustained reentrant spiral waves of SD that progressively enlarge the lesions. Furthermore, we show that the degeneration of the macula under hypoglycemic conditions can be prevented by blocking reentrant spiral SDs or by blocking caspases. The observation that spontaneous formation of reentrant spiral SD waves leads to the development of progressive retinal lesions under conditions of hypoglycemia establishes a potential role of SD in initiation and progression of macular degeneration, one of the leading causes of visual disability worldwide. PMID- 22308471 TI - Nerve growth factor regulates axial rotation during early stages of chick embryo development. AB - Nerve growth factor (NGF) was discovered because of its neurotrophic actions on sympathetic and sensory neurons in the developing chicken embryo. NGF was subsequently found to influence and regulate the function of many neuronal and non neuronal cells in adult organisms. Little is known, however, about the possible actions of NGF during early embryonic stages. However, mRNAs encoding for NGF and its receptors TrkA and p75(NTR) are expressed at very early stages of avian embryo development, before the nervous system is formed. The question, therefore, arises as to what might be the functions of NGF in early chicken embryo development, before its well-established actions on the developing sympathetic and sensory neurons. To investigate possible roles of NGF in the earliest stages of development, stage HH 11-12 chicken embryos were injected with an anti-NGF antibody (mAb alphaD11) that binds mature NGF with high affinity. Treatment with anti-NGF, but not with a control antibody, led to a dose-dependent inversion of the direction of axial rotation. This effect of altered rotation after anti NGF injection was associated with an increased cell death in somites. Concurrently, a microarray mRNA expression analysis revealed that NGF neutralization affects the expression of genes linked to the regulation of development or cell proliferation. These results reveal a role for NGF in early chicken embryo development and, in particular, in the regulation of somite survival and axial rotation, a crucial developmental process linked to left-right asymmetry specification. PMID- 22308472 TI - Role of histone deacetylases in transcription factor regulation and cell cycle modulation in endothelial cells in response to disturbed flow. AB - Vascular endothelial cells (ECs) are exposed to different flow patterns (i.e., disturbed vs. laminar), and the associated oscillatory shear stress (OSS) or pulsatile shear stress (PSS) lead to differential responses. We investigated the roles of class I and II histone deacetylases (HDAC-1/2/3 and HDAC-5/7, respectively) in regulating NF-E2-related factor-2 (Nrf2) and Kruppel-like factor 2 (KLF2), two transcription factors governing many shear-responsive genes, and the cell cycle in ECs in response to OSS. Application of OSS (0.5 +/- 4 dynes/cm(2)) to cultured ECs sustainably up-regulated class I and II HDACs and their nuclear accumulation, whereas PSS (12 +/- 4 dynes/cm(2)) induced phosphorylation-dependent nuclear export of class II HDACs. En face immunohistochemical examination of rat aortic arch and experimentally stenosed abdominal aorta revealed high HDAC-2/3/5 levels in ECs in areas exposed to disturbed flow. OSS induced the association of HDAC-1/2/3 with Nrf2 and HDAC 3/5/7 with myocyte enhancer factor-2; deacetylation of these factors led to down regulation of antioxidant gene NAD(P)H quinone oxidoreductase-1 (NQO1) and KLF2. HDAC-1/2/3- and HDAC-3/5/7-specific small interfering RNAs eliminated the OSS induced down-regulation of NQO1 and KLF2, respectively. OSS up-regulated cyclin A and down-regulated p21(CIP1) in ECs and induced their proliferation; these effects were mediated by HDAC-1/2/3. Intraperitoneal administration of the class I-specific HDAC inhibitor valproic acid into bromodeoxyuridine (BrdU)-infused rats inhibited the increased EC uptake of BrdU at poststenotic sites. The OSS induced HDAC signaling and EC responses are mediated by phosphatidylinositol 3 kinase/Akt. Our findings demonstrate the important roles of different groups of HDACs in regulating the oxidative, inflammatory, and proliferative responses of ECs to disturbed flow with OSS. PMID- 22308473 TI - The protein SdhA maintains the integrity of the Legionella-containing vacuole. AB - Legionella pneumophila directs the formation of a specialized vacuole within host cells, dependent on protein substrates of the Icm/Dot translocation system. Survival of the host cell is essential for intracellular replication of L. pneumophila. Strains lacking the translocated substrate SdhA are defective for intracellular replication and activate host cell death pathways in primary macrophages. To understand how SdhA promotes evasion of death pathways, we performed a mutant hunt to identify bacterial suppressors of the DeltasdhA growth defect. We identified the secreted phospholipase PlaA as key to activation of death pathways by the DeltasdhA strain. Based on homology between PlaA and SseJ, a Salmonella protein associated with vacuole degradation, we determined the roles of SdhA and PlaA in controlling vacuole integrity. In the absence of sdhA, the Legionella-containing vacuole was unstable, resulting in access to the host cytosol. Both vacuole disruption and host cell death were largely dependent on PlaA. Consistent with these observations, the DeltasdhA strain colocalized with galectin-3, a marker of vacuole rupture, in a PlaA-dependent process. Access of DeltasdhA strains to the macrophage cytosol triggered multiple responses in the host cell, including degradation of bacteria, induction of the type I IFN response, and activation of inflammasomes. Therefore, we have demonstrated that the Legionella-containing vacuole is actively stabilized by the SdhA protein during intracellular replication. This vacuolar niche affords the bacterium protection from cytosolic host factors that degrade bacteria and initiate immune responses. PMID- 22308474 TI - H5N1 influenza viruses: facts, not fear. AB - The ongoing controversy over publication of two studies involving the transmission in ferrets of H5N1 (H5) subtype influenza viruses and the recommendations of the National Science Advisory Board for Biosecurity to redact key details in the manuscripts call for an examination of relevant scientific facts. In addition, there are calls in the media to destroy the viruses, curtail future research in this area, and protect the public from such "frightening" research efforts. Fear needs to be put to rest with solid science and not speculation. PMID- 22308475 TI - Functional evidence that a recently evolved Drosophila sperm-specific gene boosts sperm competition. AB - In many species, both morphological and molecular traits related to sex and reproduction evolve faster in males than in females. Ultimately, rapid male evolution relies on the acquisition of genetic variation associated with differential reproductive success. Many newly evolved genes are associated with novel functions that might enhance male fitness. However, functional evidence of the adaptive role of recently originated genes in males is still lacking. The Sperm dynein intermediate chain multigene family, which encodes a Sperm dynein intermediate chain presumably involved in sperm motility, originated from complex genetic rearrangements in the lineage that leads to Drosophila melanogaster within the last 5.4 million years since its split from Drosophila simulans. We deleted all the members of this multigene family resident on the X chromosome of D. melanogaster by chromosome engineering and found that, although the deletion does not result in a reduction of progeny number, it impairs the competence of the sperm in the presence of sperm from wild-type males. Therefore, the Sperm dynein intermediate chain multigene family contributes to the differential reproductive success among males and illustrates precisely how quickly a new gene function can be incorporated into the genetic network of a species. PMID- 22308476 TI - Bortezomib interferes with C-KIT processing and transforms the t(8;21)-generated fusion proteins into tumor-suppressing fragments in leukemia cells. AB - The boronic acid dipeptide bortezomib inhibits the chymotrypsin-like activity of the 26S proteasome and shows significant therapeutic efficacy in multiple myeloma. However, recent studies suggest that bortezomib may have more complex mechanisms of action in treating cancer. We report here that the endocytosis and lysosomal degradation of the receptor tyrosine kinase C-KIT are required for bortezomib- but not tyrosine kinase inhibitor imatinib-caused apoptosis of t(8;21) leukemia and gastrointestinal stromal tumor cells, suggesting that C-KIT may recruit an apoptosis initiator. We show that C-KIT binds and phosphorylates heat shock protein 90beta (Hsp90beta), which sequestrates apoptotic protease activating factor 1 (Apaf-1). Bortezomib dephosphorylates pHsp90beta and releases Apaf-1. Although the activated caspase-3 is not sufficient to cause marked apoptosis, it cleaves the t(8;21) generated acute myeloid leukemia 1-eight twenty one (AML1-ETO) and AML1-ETO9a fusion proteins, with production of cleavage fragments that perturb the functions of the parental oncoproteins and further contribute to apoptosis. Notably, bortezomib exerts potent therapeutic efficacy in mice bearing AML1-ETO9a-driven leukemia. These data show that C-KIT-pHsp90beta Apaf-1 cascade is critical for some malignant cells to evade apoptosis, and the clinical therapeutic potentials of bortezomib in C-KIT-driven neoplasms should be further explored. PMID- 22308477 TI - EBV LMP1: New and shared pathways to NF-kappaB activation. PMID- 22308478 TI - Hallucinogen actions on human brain revealed. PMID- 22308479 TI - RNA modeling, naturally. PMID- 22308480 TI - Are cardiorespiratory complications a question of epigenetics? PMID- 22308481 TI - Retroviruses push the envelope for mammalian placentation. PMID- 22308482 TI - A long noncoding RNA regulates photoperiod-sensitive male sterility, an essential component of hybrid rice. AB - Hybrid rice has greatly contributed to the global increase of rice productivity. A major component that facilitated the development of hybrids was a mutant showing photoperiod-sensitive male sterility (PSMS) with its fertility regulated by day length. Transcriptome studies have shown that large portions of the eukaryotic genomic sequences are transcribed to long noncoding RNAs (lncRNAs). However, the potential roles for only a few lncRNAs have been brought to light at present. Thus, great efforts have to be invested to understand the biological functions of lncRNAs. Here we show that a lncRNA of 1,236 bases in length, referred to as long-day-specific male-fertility-associated RNA (LDMAR), regulates PSMS in rice. We found that sufficient amount of the LDMAR transcript is required for normal pollen development of plants grown under long-day conditions. A spontaneous mutation causing a single nucleotide polymorphism (SNP) between the wild-type and mutant altered the secondary structure of LDMAR. This change brought about increased methylation in the putative promoter region of LDMAR, which reduced the transcription of LDMAR specifically under long-day conditions, resulting in premature programmed cell death (PCD) in developing anthers, thus causing PSMS. Thus, a lncRNA could directly exert a major effect on a trait like a structure gene, and a SNP could alter the function of a lncRNA similar to amino acid substitution in structural genes. Molecular elucidating of PSMS has important implications for understanding molecular mechanisms of photoperiod regulation of many biological processes and also for developing male sterile germplasms for hybrid crop breeding. PMID- 22308483 TI - Serotype-independent pneumococcal experimental vaccines that induce cellular as well as humoral immunity. AB - For prevention of Streptococcus pneumoniae (pneumococcus) infections in infancy, protein-conjugated capsular polysaccharide vaccines provide serotype-specific, antibody-mediated immunity but do not cover all of the 90+ capsule serotypes. Therefore, microbiologists have sought protective noncapsular antigens common to all strains. Alternatively, we investigated killed cells of a noncapsulated strain, which expose many such common antigens. Given to mice intranasally, this vaccine elicits antibody-independent, CD4+ T lymphocyte-dependent accelerated clearance of pneumococci of various serotypes from the nasopharynx mediated by the cytokine IL-17A. Such immunity may reproduce the natural resistance that develops in infants before capsular antibodies arise. Given by injection, the killed cell vaccine induces bifunctional immunity: plasma antibodies protective against fatal pneumonia challenge, as well as IL-17A-mediated nasopharyngeal clearance. Human testing of this inexpensive candidate vaccine by intramuscular injection is planned. Bacterial cellular vaccines are complex--a challenge for reproducibility. However, when several known protective antigens were deleted, the killed pneumococcal vaccine was still protective. This antigenic redundancy may prevent vaccine escape variants by recombinational loss, which is frequent in pneumococcus. Biochemically defined immunogens with bifunctional activity have also been devised. These immunogens are three-component conjugates in which cell wall teichoic acid (a common antigen capable of T cell activation) is coupled to a genetic fusion of two common pneumococcal proteins: a protective surface antigen and a derivative of pneumolysin, which provides TLR4 agonist activity and induces antitoxic immunity. Such constructs induce accelerated clearance when given intranasally and induce both immune mechanisms when injected. The defined composition permits analysis of structure-function activity. PMID- 22308484 TI - Characterization of thrombopoietin (TPO)-responsive progenitor cells in adult mouse bone marrow with in vivo megakaryocyte and erythroid potential. AB - Hematopoietic progenitor cells are the progeny of hematopoietic stem cells that coordinate the production of precise numbers of mature blood cells of diverse functional lineages. Identification of cell-surface antigen expression associated with hematopoietic lineage restriction has allowed prospective isolation of progenitor cells with defined hematopoietic potential. To clarify further the cellular origins of megakaryocyte commitment, we assessed the in vitro and in vivo megakaryocyte and platelet potential of defined progenitor populations in the adult mouse bone marrow. We show that megakaryocytes arise from CD150(+) bipotential progenitors that display both platelet- and erythrocyte-producing potential in vivo and that can develop from the Flt3(-) fraction of the pregranulocyte-macrophage population. We define a bipotential erythroid megakaryocyte progenitor population, the CD150(+)CD9(lo)endoglin(lo) fraction of Lin(-)cKit(+)IL7 receptor alpha(-)FcgammaRII/III(lo)Sca1(-) cells, which contains the bulk of the megakaryocyte colony-forming capacity of the bone marrow, including bipotential megakaryocyte-erythroid colony-forming capacity, and can generate both erythrocytes and platelets efficiently in vivo. This fraction is distinct from the CD150(+)CD9(hi)endoglin(lo) fraction, which contains bipotential precursors with characteristics of increased megakaryocytic maturation, and the CD150(+)CD9(lo)endoglin(hi) fraction, which contains erythroid lineage-committed cells. Finally, we demonstrate that bipotential erythroid-megakaryocyte progenitor and CD150(+)CD9(hi)endoglin(lo) cells are TPO responsive and that the latter population specifically expands in the recovery from thrombocytopenia induced by anti-platelet serum. PMID- 22308485 TI - Modeling hepatitis C virus infection using human induced pluripotent stem cells. AB - Human pathogens impact patient health through a complex interplay with the host, but models to study the role of host genetics in this process are limited. Human induced pluripotent stem cells (iPSCs) offer the ability to produce host-specific differentiated cells and thus have the potential to transform the study of infectious disease; however, no iPSC models of infectious disease have been described. Here we report that hepatocyte-like cells derived from iPSCs support the entire life cycle of hepatitis C virus, including inflammatory responses to infection, enabling studies of how host genetics impact viral pathogenesis. PMID- 22308486 TI - Hypertension with or without adrenal hyperplasia due to different inherited mutations in the potassium channel KCNJ5. AB - We recently implicated two recurrent somatic mutations in an adrenal potassium channel, KCNJ5, as a cause of aldosterone-producing adrenal adenomas (APAs) and one inherited KCNJ5 mutation in a Mendelian form of early severe hypertension with massive adrenal hyperplasia. The mutations identified all altered the channel selectivity filter, producing increased Na(+) conductance and membrane depolarization, the signal for aldosterone production and proliferation of adrenal glomerulosa cells. We report herein members of four kindreds with early onset primary aldosteronism of unknown cause. Sequencing of KCNJ5 revealed that affected members of two kindreds had KCNJ5(G151R) mutations, identical to one of the prevalent recurrent mutations in APAs. These individuals had severe progressive aldosteronism and hyperplasia requiring bilateral adrenalectomy in childhood for blood pressure control. Affected members of the other two kindreds had KCNJ5(G151E) mutations, which are not seen in APAs. These subjects had easily controlled hypertension and no evidence of hyperplasia. Surprisingly, electrophysiology of channels expressed in 293T cells demonstrated that KCNJ5(G151E) was the more extreme mutation, producing a much larger Na(+) conductance than KCNJ5(G151R), resulting in rapid Na(+)-dependent cell lethality. We infer that this increased lethality limits adrenocortical cell mass and the severity of aldosteronism in vivo, accounting for the milder phenotype among these patients. These findings demonstrate striking variations in phenotypes and clinical outcome resulting from different mutations of the same amino acid in KCNJ5 and have implications for the diagnosis and pathogenesis of primary aldosteronism with and without adrenal hyperplasia. PMID- 22308487 TI - Glut1-mediated glucose transport regulates HIV infection. AB - Cell cycle entry is commonly considered to positively regulate HIV-1 infection of CD4 T cells, raising the question as to how quiescent lymphocytes, representing a large portion of the viral reservoir, are infected in vivo. Factors such as the homeostatic cytokine IL-7 have been shown to render quiescent T cells permissive to HIV-1 infection, presumably by transiently stimulating their entry into the cell cycle. However, we show here that at physiological oxygen (O(2)) levels (2 5% O(2) tension in lymphoid organs), IL-7 stimulation generates an environment permissive to HIV-1 infection, despite a significantly attenuated level of cell cycle entry. We identify the IL-7-induced increase in Glut1 expression, resulting in augmented glucose uptake, as a key factor in rendering these T lymphocytes susceptible to HIV-1 infection. HIV-1 infection of human T cells is abrogated either by impairment of Glut1 signal transduction or by siRNA-mediated Glut1 down regulation. Consistent with this, we show that the susceptibility of human thymocyte subsets to HIV-1 infection correlates with Glut1 expression; single round infection is markedly higher in the Glut1-expressing double-positive thymocyte population than in any of the Glut1-negative subsets. Thus, our studies reveal the Glut1-mediated metabolic pathway as a critical regulator of HIV-1 infection in human CD4 T cells and thymocytes. PMID- 22308488 TI - Membrane-localized beta-subunits alter the PIP2 regulation of high-voltage activated Ca2+ channels. AB - The beta-subunits of voltage-gated Ca(2+) (Ca(V)) channels regulate the functional expression and several biophysical properties of high-voltage activated Ca(V) channels. We find that Ca(V) beta-subunits also determine channel regulation by the membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP(2)). When Ca(V)1.3, -2.1, or -2.2 channels are cotransfected with the beta3 subunit, a cytosolic protein, they can be inhibited by activating a voltage sensitive lipid phosphatase to deplete PIP(2). When these channels are coexpressed with a beta2a-subunit, a palmitoylated peripheral membrane protein, the inhibition is much smaller. PIP(2) sensitivity could be increased by disabling the two palmitoylation sites in the beta2a-subunit. To further test effects of membrane targeting of Ca(V) beta-subunits on PIP(2) regulation, the N terminus of Lyn was ligated onto the cytosolic beta3-subunit to confer lipidation. This chimera, like the Ca(V) beta2a-subunit, displayed plasma membrane localization, slowed the inactivation of Ca(V)2.2 channels, and increased the current density. In addition, the Lyn-beta3 subunit significantly decreased Ca(V) channel inhibition by PIP(2) depletion. Evidently lipidation and membrane anchoring of Ca(V) beta-subunits compete with the PIP(2) regulation of high-voltage-activated Ca(V) channels. Compared with expression with Ca(V) beta3 subunits alone, inhibition of Ca(V)2.2 channels by PIP(2) depletion could be significantly attenuated when beta2a was coexpressed with beta3. Our data suggest that the Ca(V) currents in neurons would be regulated by membrane PIP(2) to a degree that depends on their endogenous beta-subunit combinations. PMID- 22308489 TI - Functional redundancy between repair factor XLF and damage response mediator 53BP1 in V(D)J recombination and DNA repair. AB - The classical nonhomologous DNA end-joining (C-NHEJ) double-strand break (DSB) repair pathway in mammalian cells maintains genome stability and is required for V(D)J recombination and lymphocyte development. Mutations in the XLF C-NHEJ factor or ataxia telangiectasia-mutated (ATM) DSB response protein cause radiosensitivity and immunodeficiency in humans. Although potential roles for XLF in C-NHEJ are unknown, ATM activates a general DSB response by phosphorylating substrates, including histone H2AX and 53BP1, which are assembled into chromatin complexes around DSBs. In mice, C-NHEJ, V(D)J recombination, and lymphocyte development are, at most, modestly impaired in the absence of XLF or ATM, but are severely impaired in the absence of both. Redundant functions of XLF and ATM depend on ATM kinase activity; correspondingly, combined XLF and H2AX deficiency severely impairs V(D)J recombination, even though H2AX deficiency alone has little impact on this process. These and other findings suggest that XLF may provide functions that overlap more broadly with assembled DSB response factors on chromatin. As one test of this notion, we generated mice and cells with a combined deficiency for XLF and 53BP1. In this context, 53BP1 deficiency, although leading to genome instability, has only modest effects on V(D)J recombination or lymphocyte development. Strikingly, we find that combined XLF/53BP1 deficiency in mice severely impairs C-NHEJ, V(D)J recombination, and lymphocyte development while also leading to general genomic instability and growth defects. We conclude that XLF is functionally redundant with multiple members of the ATM-dependent DNA damage response in facilitating C-NHEJ and discuss implications of our findings for potential functions of these factors. PMID- 22308490 TI - Drivers and hotspots of extinction risk in marine mammals. AB - The world's oceans are undergoing profound changes as a result of human activities. However, the consequences of escalating human impacts on marine mammal biodiversity remain poorly understood. The International Union for the Conservation of Nature (IUCN) identifies 25% of marine mammals as at risk of extinction, but the conservation status of nearly 40% of marine mammals remains unknown due to insufficient data. Predictive models of extinction risk are crucial to informing present and future conservation needs, yet such models have not been developed for marine mammals. In this paper, we: (i) used powerful machine-learning and spatial-modeling approaches to understand the intrinsic and extrinsic drivers of marine mammal extinction risk; (ii) used this information to predict risk across all marine mammals, including IUCN "Data Deficient" species; and (iii) conducted a spatially explicit assessment of these results to understand how risk is distributed across the world's oceans. Rate of offspring production was the most important predictor of risk. Additional predictors included taxonomic group, small geographic range area, and small social group size. Although the interaction of both intrinsic and extrinsic variables was important in predicting risk, overall, intrinsic traits were more important than extrinsic variables. In addition to the 32 species already on the IUCN Red List, our model identified 15 more species, suggesting that 37% of all marine mammals are at risk of extinction. Most at-risk species occur in coastal areas and in productive regions of the high seas. We identify 13 global hotspots of risk and show how they overlap with human impacts and Marine Protected Areas. PMID- 22308492 TI - QnAs with Richard T. Durrett. PMID- 22308491 TI - Robust chromosomal DNA repair via alternative end-joining in the absence of X-ray repair cross-complementing protein 1 (XRCC1). AB - Classical nonhomologous DNA end-joining (C-NHEJ), which is a major DNA double strand break (DSB) repair pathway in mammalian cells, plays a dominant role in joining DSBs during Ig heavy chain (IgH) class switch recombination (CSR) in activated B lymphocytes. However, in B cells deficient for one or more requisite C-NHEJ factors, such as DNA ligase 4 (Lig4) or XRCC4, end-joining during CSR occurs by a distinct alternative end-joining (A-EJ) pathway. A-EJ also has been implicated in joining DSBs found in oncogenic chromosomal translocations. DNA ligase 3 (Lig3) and its cofactor XRCC1 are widely considered to be requisite A-EJ factors, based on biochemical studies or extrachromosomal substrate end-joining studies. However, potential roles for these factors in A-EJ of endogenous chromosomal DSBs have not been tested. Here, we report that Xrcc1 inactivation via conditional gene-targeted deletion in WT or XRCC4-deficient primary B cells does not have an impact on either CSR or IgH/c-myc translocations in activated B lymphocytes. Indeed, homozygous deletion of Xrcc1 does not impair A-EJ of I-SceI induced DSBs in XRCC4-deficient pro-B-cell lines. Correspondingly, substantial depletion of Lig3 in Lig4-deficient primary B cells or B-cell lines does not impair A-EJ of CSR-mediated DSBs or formation of IgH/c-myc translocations. Our findings firmly demonstrate that XRCC1 is not a requisite factor for A-EJ of chromosomal DSBs and raise the possibility that DNA ligase 1 (Lig1) may contribute more to A-EJ than previously considered. PMID- 22308493 TI - QnAs with Arthur L. Horwich. Interview by Prashant Nair. PMID- 22308494 TI - Vezf1 protein binding sites genome-wide are associated with pausing of elongating RNA polymerase II. AB - The protein Vezf1 plays multiple roles important for embryonic development. In Vezf1(-/-) mouse embryonic stem (mES) cells, our earlier data showed widespread changes in gene-expression profiles, including decreased expression of the full length active isoform of Dnmt3b methyltransferase and concomitant genome-wide reduction in DNA methylation. Here we show that in HeLaS3 cells there is a strong genome-wide correlation between Vezf1 binding and peaks of elongating Ser2-P RNA polymerase (Pol) ll, reflecting Vezf1-dependent slowing of elongation. In WT mES cells, the elongating form of RNA pol II accumulates near Vezf1 binding sites within the dnmt3b gene and at several other Vezf1 sites, and this accumulation is significantly reduced at these sites in Vezf1(-/-) mES cells. Depending upon genomic location, Vezf1-mediated Pol II pausing can have different regulatory roles in transcription and splicing. We find examples of genes in which Vezf1 binding sites are located near cassette exons, and in which loss of Vezf1 leads to a change in the relative abundance of alternatively spliced messages. We further show that Vezf1 interacts with Mrg15/Mrgbp, a protein that recognizes H3K36 trimethylation, consistent with the role of histone modifications at alternatively spliced sites. PMID- 22308495 TI - Profile of Robert B. Goldberg. PMID- 22308496 TI - Spatial navigation impairment is proportional to right hippocampal volume. AB - Cognitive deficits in older adults attributable to Alzheimer's disease (AD) pathology are featured early on by hippocampal impairment. Among these individuals, deterioration in spatial navigation, manifested by poor hippocampus dependent allocentric navigation, may occur well before the clinical onset of dementia. Our aim was to determine whether allocentric spatial navigation impairment would be proportional to right hippocampal volume loss irrespective of general brain atrophy. We also contrasted the respective spatial navigation scores of the real-space human Morris water maze with its corresponding 2D computer version. We included 42 cognitively impaired patients with either amnestic mild cognitive impairment (n = 23) or mild and moderate AD (n = 19), and 14 cognitively intact older controls. All participants underwent 1.5T MRI brain scanning with subsequent automatic measurement of the total brain and hippocampal (right and left) volumes. Allocentric spatial navigation was tested in the real space version of the human Morris water maze and in its corresponding computer version. Participants used two navigational cues to locate an invisible goal independent of the start position. We found that smaller right hippocampal volume was associated with poorer navigation performance in both the real-space (beta = 0.62, P < 0.001) and virtual (beta = -0.43, P = 0.026) versions, controlling for demographic variables, total brain and left hippocampal volumes. In subsequent analyses, the results were significant in cognitively impaired (P <= 0.05) but not in cognitively healthy (P > 0.59) subjects. The respective real-space and virtual scores strongly correlated with each other. Our findings indicate that the right hippocampus plays a critical role in allocentric navigation, particularly when cognitive impairment is present. PMID- 22308497 TI - Chondroitinase ABC promotes selective reactivation of somatosensory cortex in squirrel monkeys after a cervical dorsal column lesion. AB - After large but incomplete lesions of ascending dorsal column afferents in the cervical spinal cord, the hand representation in the contralateral primary somatosensory cortex (area 3b) of monkeys is largely or completely unresponsive to touch on the hand. However, after weeks of spontaneous recovery, considerable reactivation of the hand territory in area 3b can occur. Because the reactivation process likely depends on the sprouting of remaining axons from the hand in the cuneate nucleus of the lower brainstem, we sought to influence cortical reactivation by treating the cuneate nucleus with an enzyme, chondroitinase ABC, that digests perineuronal nets, promoting axon sprouting. Dorsal column lesions were placed at a spinal cord level (C5/C6) that allowed a portion of ascending afferents from digit 1 to survive in squirrel monkeys. After 11-12 wk of recovery, the contralateral forelimb cortex was reactivated by stimulating digit 1 more extensively in treated monkeys than in control monkeys. The results are consistent with the proposal that the treatment enhances the sprouting of digit 1 afferents in the cuneate nucleus and that this sprouting allowed these preserved inputs to activate cortex more effectively. PMID- 22308498 TI - Reduced release probability prevents vesicle depletion and transmission failure at dynamin mutant synapses. AB - Endocytic recycling of synaptic vesicles after exocytosis is critical for nervous system function. At synapses of cultured neurons that lack the two "neuronal" dynamins, dynamin 1 and 3, smaller excitatory postsynaptic currents are observed due to an impairment of the fission reaction of endocytosis that results in an accumulation of arrested clathrin-coated pits and a greatly reduced synaptic vesicle number. Surprisingly, despite a smaller readily releasable vesicle pool and fewer docked vesicles, a strong facilitation, which correlated with lower vesicle release probability, was observed upon action potential stimulation at such synapses. Furthermore, although network activity in mutant cultures was lower, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity was unexpectedly increased, consistent with the previous report of an enhanced state of synapsin 1 phosphorylation at CaMKII-dependent sites in such neurons. These changes were partially reversed by overnight silencing of synaptic activity with tetrodotoxin, a treatment that allows progression of arrested endocytic pits to synaptic vesicles. Facilitation was also counteracted by CaMKII inhibition. These findings reveal a mechanism aimed at preventing synaptic transmission failure due to vesicle depletion when recycling vesicle traffic is backed up by a defect in dynamin-dependent endocytosis and provide new insight into the coupling between endocytosis and exocytosis. PMID- 22308499 TI - Tcl1 protein functions as an inhibitor of de novo DNA methylation in B-cell chronic lymphocytic leukemia (CLL). AB - B-cell chronic lymphocytic leukemia (CLL) is the most common human leukemia. Deregulation of the T-cell leukemia/lymphoma 1 oncogene (TCL1) in mouse B cells causes a CD5(+) leukemia similar to aggressive human CLL. To examine the mechanisms by which Tcl1 protein exerts its oncogenic activity in B cells, we performed proteomics experiments to identify its interacting partners. We found that Tcl1 physically interacts with de novo DNA methylthansferases Dnmt3A and Dnmt3B. We further investigated the effects of Tcl1 up-regulation on the enzymatic activity of Dnmt3A and found that Tcl1 overexpression drastically inhibits Dnmt3A function. In addition, B cells from TCL1 transgenic mice showed a significant decrease in DNA methylation compared with WT controls. Similarly, CLL samples with high Tcl1 expression showed a decrease in DNA methylation compared with CLL samples with low Tcl1 expression. Given the previous reports of inactivating mutations of DNMT3A in acute myelogenous leukemia and myelodysplastic syndrome, our results suggest that inhibition of de novo DNA methylation may be a common oncogenic mechanism in leukemogenesis. PMID- 22308500 TI - Hemagglutinin stalk antibodies elicited by the 2009 pandemic influenza virus as a mechanism for the extinction of seasonal H1N1 viruses. AB - After the emergence of pandemic influenza viruses in 1957, 1968, and 2009, existing seasonal viruses were observed to be replaced in the human population by the novel pandemic strains. We have previously hypothesized that the replacement of seasonal strains was mediated, in part, by a population-scale boost in antibodies specific for conserved regions of the hemagglutinin stalk and the viral neuraminidase. Numerous recent studies have shown the role of stalk specific antibodies in neutralization of influenza viruses; the finding that stalk antibodies can effectively neutralize virus alters the existing dogma that influenza virus neutralization is mediated solely by antibodies that react with the globular head of the viral hemagglutinin. The present study explores the possibility that stalk-specific antibodies were boosted by infection with the 2009 H1N1 pandemic virus and that those antibodies could have contributed to the disappearance of existing seasonal H1N1 influenza virus strains. To study stalk specific antibodies, we have developed chimeric hemagglutinin constructs that enable the measurement of antibodies that bind the hemagglutinin protein and neutralize virus but do not have hemagglutination inhibition activity. Using these chimeric hemagglutinin reagents, we show that infection with the 2009 pandemic H1N1 virus elicited a boost in titer of virus-neutralizing antibodies directed against the hemagglutinin stalk. In addition, we describe assays that can be used to measure influenza virus-neutralizing antibodies that are not detected in the traditional hemagglutination inhibition assay. PMID- 22308501 TI - Go2 G protein mediates galanin inhibitory effects on insulin release from pancreatic beta cells. AB - The neuropeptide galanin regulates numerous physiological activities in the body, including feeding and metabolism, learning and memory, nociception and spinal reflexes, and anxiety and related behaviors. Modulation of blood glucose levels by suppressing insulin release was the first reported activity for galanin. This inhibition was mediated by one or more pertussis toxin-sensitive G proteins of the G(i/o) subfamily. However, the molecular identities of the specific G protein(s) and intracellular effectors have not been fully revealed. Recently, we demonstrated that mice lacking G(o)2, but not other members of the G(i/o) protein family, secrete more insulin than controls upon glucose challenge, indicating that G(o)2 is a major transducer for the inhibitory regulation of insulin secretion. In this study, we investigated galanin signaling mechanisms in beta cells using cell biological and electrophysiological approaches. We found that islets lacking G(o)2, but not other G(i/o) proteins, lose the inhibitory effect of galanin on insulin release. Potentiation of ATP-sensitive potassium (K(ATP)) and inhibition of calcium currents by galanin were disrupted by anti-G(o)2alpha antibodies. Galanin actions on K(ATP) and calcium currents were completely lost in G(o)2(-/-) beta cells. Furthermore, the hyperglycemic effect of galanin is also blunted in G(o)2(-/-) mice. Our results demonstrate that G(o)2 mediates the inhibition of insulin release by galanin by regulating both K(ATP) and Ca(2+) channels in mice. Our findings provide insight into galanin's action in glucose homeostasis. The results may also be relevant to the understanding of galanin signaling in other biological systems, especially the central nervous system. PMID- 22308502 TI - Plant secondary siRNA production determined by microRNA-duplex structure. AB - Processing of microRNA (miRNA) precursors results in the release of a double stranded miRNA/miRNA* duplex. The miRNA or guide strand, is loaded onto the Argonaute (AGO) effector, and the miRNA* or passenger strand is typically degraded. The loaded AGO-containing RNA-induced silencing complex specifically recognizes a target mRNA, leading to its degradation or translational inhibition. In plants, miRNA-mediated cleavage of a target triggers in some cases the production of secondary small interfering RNAs (siRNAs), which in turn can silence other genes in trans. This alternative pathway depends on the length of the miRNA and the specific AGO in the effector complex. However, 22-nt miRNAs are sufficient, but not essential for this pathway. Using a combination of computational and experimental approaches, we show that transitivity can be triggered when the small RNA that is not retained in AGO is 22-nt long. Moreover, we demonstrate that asymmetrically positioned bulged bases in the miRNA:miRNA* duplex, regardless of miRNA or miRNA* length, are sufficient for the initiation of transitivity. We propose that the RNA-induced silencing complex reprogramming occurs during the early steps of miRNA loading, before the miRNA duplex is disassembled and the guide strand is selected. PMID- 22308503 TI - Shifting pharmacology of nicotine use and withdrawal: breaking the cycle of drug abuse. PMID- 22308505 TI - MicroRNA expression by an oncogenic retrovirus. PMID- 22308508 TI - Quantification and visualization of phosphoinositides by quantum dot-labeled specific binding-domain probes. AB - Phosphoinositides (PI) play important regulatory roles in cell physiology. Localization and quantitation of PIs within the cell is necessary to understand their precise function. Currently, ectopic expression of green fluorescent protein (GFP)-fused PI-binding domains is used to visualize PIs localized to the cell membrane. However, ectopically expressed PI-binding domains may compete with endogenous binding proteins, thus altering the physiological functions of the PIs. Here, we establish a novel method for quantification and visualization of PIs in cells and tissue samples using PI-binding domains labeled with quantum dots (Qdot) as specific probes. This method allowed us to simultaneously quantify three distinct PIs, phosphatidylinositol 3,4,5-triphosphatase [PtdIns(3,4,5)P(3)), PtdIns(3,4)P(2), and PtdIns(4,5)P(2), in crude acidic lipids extracted from insulin-stimulated cells. In addition, the method allowed the PIs to be visualized within fixed cells and tissues. Sequential and spatial changes in PI production and distribution were detected in platelet-derived growth factor (PDGF)-stimulated NRK49F cells. We also observed accumulation of PtdIns(3,4)P(2) at the dorsal ruffle in PDGF-stimulated NIH3T3 cells. Finally, we found PtdIns(3,4,5)P(3) was enriched in lung cancer tissues, which also showed high levels of phosphorylated Akt. Our new method to quantify and visualize PIs is expected to provide further insight into the role of lipid signaling in a wide range of cellular events. PMID- 22308509 TI - An LC/MS method for d8-beta-carotene and d4-retinyl esters: beta-carotene absorption and its conversion to vitamin A in humans. AB - The intestinal absorption and metabolism of beta-carotene is of vital importance in humans, especially in populations that obtain the majority of their vitamin A from provitamin A carotenoids. MS has provided a better understanding of the absorption of beta-carotene, the most potent provitamin A carotenoid, through the use of stable isotopes of beta-carotene. We report here an HPLC-MS method that eliminates the need for complicated sample preparation and allows us to detect and quantify newly absorbed d8-beta-carotene as well as its d4-retinyl ester metabolites in human plasma and chylomicron fractions. Both retinoids and beta carotene were recovered in a single simple extraction that did not involve saponification, thus allowing subsequent quantitation of individual fatty acyl esters of retinol. Separation of d8-beta-carotene and its d4-retinyl ester metabolites was achieved using the same C30 reversed-phase liquid chromatography followed by mass spectrometry in selected ion monitoring and negative atmospheric pressure chemical ionization modes, respectively. Total time for the two successive runs was 30 min. This HPLC-MS method allowed us to quantify the absorption of intact d8-beta-carotene as well as its extent of conversion to d4 retinyl esters in humans after consumption of a single 5 mg dose of d8-beta carotene. PMID- 22308511 TI - Disclosing pharma payments to oncologists: what will we learn? PMID- 22308512 TI - Ten years of progress in prostate cancer. PMID- 22308510 TI - Interaction between head and neck squamous cell carcinoma cells and fibroblasts in the biosynthesis of PGE2. AB - Prostaglandin (PG)E(2) is relevant in tumor biology, and interactions between tumor and stroma cells dramatically influence tumor progression. We tested the hypothesis that cross-talk between head and neck squamous cell carcinoma (HNSCC) cells and fibroblasts could substantially enhance PGE(2) biosynthesis. We observed an enhanced production of PGE(2) in cocultures of HNSCC cell lines and fibroblasts, which was consistent with an upregulation of COX-2 and microsomal PGE-synthase-1 (mPGES-1) in fibroblasts. In cultured endothelial cells, medium from fibroblasts treated with tumor cell-conditioned medium induced in vitro angiogenesis, and in tumor cell induced migration and proliferation, these effects were sensitive to PGs inhibition. Proteomic analysis shows that tumor cells released IL-1, and tumor cell-induced COX-2 and mPGES-1 were suppressed by the IL-1-receptor antagonist. IL-1alpha levels were higher than those of IL-1beta in the tumor cell-conditioning medium and in the secretion from samples obtained from 20 patients with HNSCC. Fractionation of tumor cell-conditioning media indicated that tumor cells secreted mature and unprocessed forms of IL-1. Our results support the concept that tumor-associated fibroblasts are a relevant source of PGE(2) in the tumor mass. Because mPGES-1 seems to be essential for a substantial biosynthesis of PGE(2), these findings also strengthen the concept that mPGES-1 may be ?a target for therapeutic intervention in patients with HNSCC. PMID- 22308513 TI - Diagnostic and treatment considerations when newly diagnosed breast cancer coincides with pregnancy: a case report and review of literature. AB - Breast cancer is the most common malignancy associated with pregnancy and is a rare but well-recognized complication. It is hypothesized that as more women continue to delay childbearing, the incidence of breast cancer in pregnancy will increase. Because of the lack of clinical experience with breast cancer in the setting of pregnancy, given its relative infrequency, many patients and physicians believe the diagnosis puts the life of the mother at odds with that of the fetus, but available data suggest that termination of the pregnancy does not improve the outcome for pregnant women with breast cancer. Often diagnosis is delayed because neither patient nor physician suspects malignancy. This report presents a recent case of a young primigravid woman with a newly appreciated breast mass seen at Northwestern University Feinberg School of Medicine as a means of discussing diagnostic considerations, therapeutic options, and supportive care available to the practitioner when managing a pregnant patient with breast cancer. PMID- 22308514 TI - Communicating about chemotherapy-induced nausea and vomiting: a comparison of patient and provider perspectives. AB - Despite recent progress, chemotherapy-induced nausea and vomiting (CINV), especially delayed CINV, continues to be a problem. Delayed CINV is underestimated and perceived differently by providers and patients. Communication between providers and patients about this side effect may help improve outcomes. This study identifies patients' and providers' perceptions of management and barriers to quality CINV care. Provider and patient versions of a Nausea and Vomiting Management Barriers Questionnaire were developed to address potential barriers. Providers and patients were given opportunities to add detail in open ended questions. Providers were recruited through the NCCN and the Oncology Nursing Society mailing lists. Patients who received at least 2 cycles of chemotherapy and experienced CINV were recruited through a consortium of advocacy groups. Both providers (n = 141) and patients (n = 299) completed the survey. Providers (41%) and patients (42%) agreed medication side effects were a concern, but more patients (63%) than providers (36%) tried to limit the number of medications taken (P < .0001). Many providers (67%) spontaneously reported barriers to managing CINV, with financial and patient-related factors among the most common. Few patients (10%) reported cost as a barrier, but 37% endorsed the desire "to be strong by not complaining." Barriers to communication and quality care of CINV differ between caregivers and patients. Addressing misconceptions and establishing mutually consistent goals will lead to more effective overall care. PMID- 22308516 TI - Challenges in the management of older patients with colon cancer. AB - Most patients with colon cancer are older than 65 years. Their treatment poses multiple challenges, because they may have age-related comorbidities, polypharmacy, and physical or physiologic changes associated with older age. These challenges include limited data on the ability to predict tolerance to anticancer therapy and the appropriate use of treatment modalities in the setting of comorbidity and concurrent frailty. The low number of older patients enrolled in large clinical trials results in a paucity of evidence to guide oncologists in the appropriate management of this population. In early-stage disease, clinical dilemmas arise regarding the ability of older patients to undergo successful curative surgical procedures and the risk/benefit ratio of adjuvant chemotherapy. The management of metastatic disease raises questions regarding the clinical benefit of various anticancer therapies and the role of combination therapy with possible increased toxicity in the noncurative setting. Overall, the available evidence shows that fit older patients are able to tolerate treatment and derive similar clinical benefits to younger patients. Limited data are available to guide treatment for less-fit, more-vulnerable older patients. This lack of data leads to variations in treatment patterns in older adults, making them less likely to receive standard therapies. This review provides an overview of the available data regarding the management of older adults with colon cancer in the adjuvant and metastatic settings. PMID- 22308517 TI - Treatment of non-small cell lung cancer in the older patient. AB - Lung cancer is a disease of the elderly, with a median age at diagnosis of 70 years. However, there is a dearth of good quality evidence to guide treatment in this population and most of the data are extrapolated from younger patients. Current research is directed toward establishing simplified instruments to quantify fitness of older patients for various forms of therapy. Although current evidence suggests that outcomes after standard therapy are similar to those seen in younger patients, older patients have an increased incidence of adverse events. Until better predictive markers are available to guide treatment, therapy should be individualized using available instruments, including a comprehensive geriatric assessment. If an older patient is deemed to be fit, it is reasonable to use the treatment options recommended for younger individuals. This article summarizes the available data on the treatment of non-small cell lung cancer in the older patient. PMID- 22308518 TI - Lung cancer screening. PMID- 22308519 TI - Lung cancer screening with low-dose computed tomography: costs, national expenditures, and cost-effectiveness. AB - A recent randomized trial showed that low-dose CT (LDCT) screening reduces lung cancer mortality. Health care providers need an assessment of the national budget impact and cost-effectiveness of LDCT screening before this intervention is adopted in practice. Using data from the 2009 National Health Interview Survey, CMS, and the National Lung Screening Trial (NLST), the authors performed an economic analysis of LDCT screening that includes a budget impact model, an estimate of additional costs per lung cancer death avoided attributed to screening, and a literature search of cost-effectiveness analyses of LDCT screening. They conducted a one-way sensitivity analysis, reporting expenditures in 2011 U.S. dollars, and took the health care payer and patient perspectives. LDCT screening will add $1.3 to $2.0 billion in annual national health care expenditures for screening uptake rates of 50% to 75%, respectively. However, LDCT screening will avoid up to 8100 premature lung cancer deaths at a 75% screening rate. The prevalence of smokers who qualify for screening, screening uptake rates, and cost of LDCT scan were the most influential parameters on health care expenditures. The additional cost of screening to avoid one lung cancer death is $240,000. Previous cost-effectiveness analyses have not conclusively shown that LDCT is cost-effective. LDCT screening may add substantially to the national health care expenditures. Although LDCT screening can avoid more than 8000 lung cancer deaths per year, a cost-effectiveness analysis of the NLST will be critical to determine the value of this intervention and to guide decisions about its adoption. PMID- 22308515 TI - Senior adult oncology. PMID- 22308520 TI - Setting up a lung cancer screening program. AB - This article summarizes what is known about the best practices of lung cancer screening and provides suggestions for the proper structure for institutions considering offering lung cancer screening services. Important points of emphasis include the need to confine screening to patients at highest risk, the presence of multidisciplinary teams capable of managing the high number of false-positive findings, the need for additional research on biomarkers and risk models for lung cancer, and the currently unknown cost-effectiveness of lung cancer screening on a societal level. PMID- 22308521 TI - Research priorities in geriatric oncology: addressing the needs of an aging population. PMID- 22308523 TI - Reorienting our view of particle-based adjuvants for subunit vaccines. PMID- 22308524 TI - Illuminating neuromyelitis optica pathogenesis. PMID- 22308525 TI - A Nogo signal coordinates the perfect match between myelin and axons. PMID- 22308526 TI - Phylogeny and beyond: Scientific, historical, and conceptual significance of the first tree of life. AB - In 1977, Carl Woese and George Fox published a brief paper in PNAS that established, for the first time, that the overall phylogenetic structure of the living world is tripartite. We describe the way in which this monumental discovery was made, its context within the historical development of evolutionary thought, and how it has impacted our understanding of the emergence of life and the characterization of the evolutionary process in its most general form. PMID- 22308527 TI - Woese and Fox: Life, rearranged. PMID- 22308528 TI - Lynn Margulis, 1938-2011. PMID- 22308529 TI - Construction of a prototype two-component system from the phosphorelay system TodS/TodT. AB - Two-component systems (TCSs) play key roles in the adaptation of bacteria to environmental changes. In prototype TCSs a single phosphoryl transfer between the sensor kinase and response regulator occurs, whereas phosphorelay TCSs are characterised by a His1-Asp1-His2-Asp2 phosphorylation cascade. The TodS/TodT TCS controls the expression of a toluene degradation pathway and the TodS sensor kinase operates by a three-step internal phosphorelay. Based on TodS we report the construction of a minimal form of TodS, termed as Min-TodS, that contains only three of the seven TodS domains. Min-TodS is composed of the N-terminal PAS sensor domain as well as the C-terminal dimerisation/phosphotransfer domain and catalytic domain of TodS. We have conducted a comparative analysis of the phosphorelay TCS with its prototypal derivative. We demonstrate that Min-TodS binds effector molecules with affinities comparable with those observed for TodS. Min-TodS forms a TCS with TodT and toluene increases the amount of TodT-P. In contrast to TodS, toluene does not stimulate Min-TodS autophosphorylation. The half-life of Min-TodS-P was significantly increased as compared with TodS. Analysis of TodSD500A revealed that the hydrolysis of the acylphosphate of the receiver domain is responsible for the reduced half-life of TodS. The regulation of P(todX) expression by Min-TodS/TodT and TodS/TodT in response to different effectors are compared. The Min-TodS/TodT system was characterized by a higher basal activity but a lower magnitude of response. Data will be discussed in the context that the phosphorelay system appears to be better suited for the control of a degradation pathway for toxic compounds. PMID- 22308531 TI - Anatomical and pathological findings in hearts from fetuses and infants with cardiac manifestations of neonatal lupus. AB - OBJECTIVE: The autopsy and clinical information on children dying with anti SSA/Ro-associated cardiac manifestations of neonatal lupus (cardiac NL) were examined to identify patterns of disease, gain insight into pathogenesis and enhance the search for biomarkers and preventive therapies. METHODS: A retrospective analysis evaluating reports from 18 autopsies of cardiac NL cases and clinical data from the Research Registry for Neonatal Lupus was performed. RESULTS: Of the 18 cases with autopsies, 15 had advanced heart block, including 3 who died in the second trimester, 9 in the third trimester and 3 post-natally. Three others died of cardiomyopathy without advanced block, including two dying pre-natally and one after birth. Pathological findings included fibrosis/calcification of the atrioventricular (AV) node, sinoatrial (SA) node and bundle of His, endocardial fibroelastosis (EFE), papillary muscle fibrosis, valvular disease, calcification of the atrial septum and mononuclear pancarditis. There was no association of pathology with the timing of death except that in the third-trimester deaths more valvular disease and/or extensive conduction system abnormalities were observed. Clinical rhythm did not always correlate with pathology of the conduction system, and the pre-mortem echocardiograms did not consistently detect the extent of pathology. CONCLUSION: Fibrosis of the AV node/distal conduction system is the most characteristic histopathological finding. Fibrosis of the SA node and bundle of His, EFE and valve damage are also part of the anti-Ro spectrum of injury. Discordance between echocardiograms and pathology findings should prompt the search for more sensitive methods to accurately study the phenotype of antibody damage. PMID- 22308532 TI - Menopause and schizophrenia. AB - We have come a long way from our understanding of the menopause as it was described in the 11th century by Trotula of Salerno, a female gynaecologist who said 'there are older women who give forth blood matter especially as menopause approaches them'. Yet very little is known about the impact menopause has on the mental health of women especially severe and enduring illnesses like schizophrenia. A lot of research has shown that estrogen acts as a protective factor due to its antidopaminergic properties, thus providing an explanation for the increase in risk of a new psychotic disorder during the menopause. This has further led to the hypothesis of hormone replacement therapy providing benefits in the management of these disorders in menopausal women. This review article highlights the importance of a clear understanding of this phase of life in patients suffering from or who present with a risk of developing schizophrenia. PMID- 22308533 TI - Evidence for a genetic role in varicose veins and chronic venous insufficiency. AB - There is a strong body of circumstantial evidence which implicates genetics in the aetiology and pathology of varicose veins and venous ulcer disease. The aim of this review is to consider the current knowledge of the genetic associations and the ways in which new genetic technologies may be applied to advancing our understanding of the cause and progression of these venous diseases. A number of publications have used a candidate gene approach to identify genes implicated in venous disease. Although these studies have opened up important new insights, there has been a general failure to replicate results in an independent cohort of patients. With our limited knowledge of the biological pathways involved in the pathogenesis of venous disease we are not in a strong position to formulate truly erudite a priori candidate gene hypothesis-directed studies. A genome-wide association study should therefore be considered to help further our understanding of the genetic basis of venous disease. Due to the large sample sizes required for discovery and validation, using the new generations of molecular technologies, it will be necessary to form collaborating groups in order to successfully advance the field of venous disease genetics. PMID- 22308534 TI - Sensitivity of Gram stain in the diagnosis of urethritis in men. AB - BACKGROUND: Acute urethritis is among the most common types of sexually transmitted diseases in men. The diagnosis usually requires microscopic evidence of urethritis, but sometimes urethral pathogens are detected in asymptomatic men without such evidence. The aims of this study were to assess the sensitivity of Gram stain in men with urethral symptoms and to relate it to the microorganisms isolated. METHODS: Between January 2006 and December 2007, 491 urethral samples were analysed. The authors assessed the presence of leukocytes by Gram stain and tested specifically for Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis and Trichomonas vaginalis, as well as analysing the results of conventional culture. RESULTS: The percentages of positive samples as a function of Gram category were two or less polymorphonuclear leukocytes (PMNLs)/high-power field (HPF) 25% (92/364), three to four PMNLs/HPF 32% (18/57) and five or more PMNLs/HPF 54% (38/70). Classing samples with more than two PMNLs/HPF as positive, the sensitivity, specificity and positive likelihood ratio for Gram stain were 38% (95% CI 30 to 46), 79% (95% CI 75 to 84) and 1.8 (95% CI 1.4 to 2.4), respectively. On the other hand, taking as positive five or more PMNLs/HPF, the sensitivity, specificity and positive likelihood ratio for Gram stain were 26% (95% CI 18 to 33), 91% (95% CI 87 to 94) and 2.7 (95% CI 1.8 to 4.2), respectively. The sensitivity of Gram stain to Neisseria gonorrhoeae, Chlamydia trachomatis and Ureaplasma urealyticum were 80% (95% CI 64 to 96), 23% (95% CI 8 to 39) and 11% (95% CI 2 to 20), respectively. CONCLUSION: The low sensitivity of Gram stain means that negative results do not exclude the presence of urethritis in symptomatic patients. PMID- 22308535 TI - Neuropeptide Y Leu7Pro polymorphism associated with the metabolic syndrome and its features in patients with coronary artery disease. AB - The metabolic syndrome (MetS) is characterized by constellation of clinical and biochemical features that increase the risk of cardiovascular disease. Neuropeptide Y (NPY) is a neurotransmitter and enhances the development of obesity and other aspects of MetS. We determined the association between NPY Leu7Pro polymorphism and features of MetS in Iranian patients with coronary artery disease (CAD). A total of 550 patients with CAD including individuals with (n = 184) and without MetS (n = 366) were genotyped by polymerase chain reaction restriction fragment length polymorphism. A significantly higher frequency of the Leu7Pro polymorphism was found in patients with MetS compared with the non-MetS patients (P = .001). Furthermore, there was a significant difference in Pro7 frequency between diabetics versus nondiabetics (P = .005), dyslipidemic versus nondyslipidemic (P = .04), and obese versus nonobese (P = .001) in this population. Leu7Pro polymorphism is associated with the MetS in patients with CAD. PMID- 22308536 TI - Physical, psychological, and social aspects of quality of life in filarial lymphedema patients in Colombo, Sri Lanka. AB - Quality of life (QOL) was assessed in 141 filarial lymphedema patients and 128 healthy people in the Colombo district, Sri Lanka, by administering modified, translated, and validated (in Sri Lanka) versions of the Short Form 36 health survey questionnaire (SF-36) and the 30-item General Health questionnaire (GHQ 30). The GHQ-30 assesses the current mental health status. The SF-36 measures health on 8 multi-item dimensions covering functional state, well-being, and overall evaluation of health (physical functioning, role limitations resulting from physical health problems, role limitations resulting from emotional problems, energy/fatigue, emotional well-being, social functioning, pain and general health). By SF-36, patients experienced poorer physical functioning, more role limitations resulting from physical health conditions, less emotional well being, poorer social functioning, and more pain than healthy individuals. By GHQ 30, mental well-being of healthy controls was significantly better than that of patients. The significant difference in the QOL as perceived by filarial lymphedema patients and healthy individuals reiterates the importance of morbidity control in patients affected by this disease. PMID- 22308537 TI - Factors associated with tobacco use among adolescents in India: results from the Global Youth Tobacco Survey, India (2000-2003). AB - OBJECTIVE: To differentiate between the different types of tobacco users and analyze the association between types of tobacco users and factors like pocket money and peer and parental influence across most of the state in India using the data obtained from Global Youth Tobacco Survey (GYTS) between 2000 and 2004. METHODOLOGY: The GYTS data encompassed a representative 2-stage probability sample of students aged 13 to 15 years across 24 states and 2 union territories in India. These students were interviewed using an anonymous, self-administered questionnaire. RESULT: A very strong association between users and pocket money was found in most of the states, with northeastern states having a very strong association-Sikkim, odds ratio (OR) = 8.43 (confidence interval [CI] = 6.08 11.69), and Manipur, OR = 5.58 (CI = 3.60-8.65)-after adjusting for close friend being smoker, close friend being smokeless tobacco user, parental influence, age, and gender. CONCLUSION: This study found a strong association between tobacco use by adolescents and having pocket money and close friends being tobacco users. PMID- 22308538 TI - Addressing the sluggish progress in reducing maternal mortality in India. AB - Although some progress has been made in India, achievement of the Fifth Millennium Development Goal (MDG5; ie, 75% reduction in maternal mortality ratio [MMR] from 1990 by 2015) target seems to be unattainable by 2015. Failure of the National Population Policy, 2000, and the National Health Policy, 2002, to reduce the MMR demanded a new direction, leading to the establishment of a National Rural Health Mission in 2005. This commentary addresses both the real achievements and the hurdles faced in India's stagnating progress in maternal health. Promotion of maternal nutrition and health education, with greater attention to emergency obstetrical care at the district subcenter and primary health care center levels, must be prioritized. These changes of focus are vital to make prenatal, delivery, and postnatal care safer with increased resources allotted to adolescents, the poor, and women living in rural areas in order to enhance maternal health and achieve the MDG target. PMID- 22308539 TI - Children's experiences of acute hospitalisation to a paediatric emergency and assessment unit--a qualitative study. AB - Short-stay treatment has become a popular form of care as a strategy to cope with increased demands on health care. There is little research that considers children's experiences of acute hospitalisation to a short-stay care facility such as a Paediatric Emergency and Assessment Unit (PEAU). This study explored the experiences of eight children aged 8-10 years. Semi-structured interviews were carried out to investigate the children's own experiences of being hospitalised in a PEAU. Thematic content analyses were used. Three major themes were identified: the children's understanding of disease, treatment and procedures; the children's experiences of health-care personnel and the PEAU and transformation of everyday life into the settings of the hospital. The children identified the hospital stay as an overall positive experience. The children took part in leisure activities as they would at home and enjoyed time together with their parents while in hospital. In their conversations with staff they adapted to professional terms that they did not necessarily understand. They did not differentiate between professionals. Further work should be considered to clarify the consequences of this. This study has provided some limited insight into the child's experiences of acute hospitalisation, which should inform nursing care. PMID- 22308540 TI - Sibling involvement in childhood chronic heart disease through a bead program. AB - In interviews with parents for the evaluation of a cardiac ward programme in a children's hospital, a number of parents mentioned the role of the Heart Beads Program in including siblings in the hospitalisation of the child with congenital heart condition (CHD). Inclusion of siblings in the events surrounding the child with the cardiac condition was of two kinds: (a) touching and explaining about the beads and the child's condition and (b) involvement in collecting and threading the beads. Discussion of the needs of siblings suggests that inclusion of siblings in activities related to the care and understanding of the CHD child as well as the creation and shaping of the family narrative is important. These cases illustrate the different ways in which siblings are involved and acknowledged and how involvement can be facilitated by a programme like Heart Beads. PMID- 22308541 TI - Jointly managing arthritis: information needs of children with juvenile idiopathic arthritis (JIA) and their parents. AB - The objective of this article is to explore information needs of children with juvenile idiopathic arthritis (JIA) and their parents in order to develop a web based psychoeducational program aimed at improving their quality of life. A qualitative study design was used. A purposive sample of children (n = 41; 8-11 years) with JIA and parents (n = 48) participated in parent-child interviews (n = 29), and four child-focus and four parent-focus group interviews. Transcribed data were organized into categories that reflected emerging themes. Findings uncovered three major themes: "living with JIA", "jointly managing JIA", and "need for a web-based program of JIA information and social Support". Subthemes for "Living with JIA" were as follows: "impact on participation", "worry and distress", and "receiving social support". Subthemes under "Jointly Managing JIA" included "obtaining JIA information", "communication and advocacy", and "strategies to manage JIA". Participants endorsed a web-based program as a way to access JIA information and social support. In order to jointly manage JIA, participants expressed the need for disease-specific information, management strategies, and social support and felt that the Internet was acceptable for delivering these disease-management strategies. Findings from this study will inform development and evaluation of an online program to help children and parents jointly manage JIA. PMID- 22308542 TI - Parental psychosocial predictors of secondhand smoke exposure (SHSe) for children with cancer. AB - Children with cancer are at greater risk for the negative consequences of secondhand smoke exposure, making the identification of predictors of exposure critical. The current study investigated the impact of parents' psychosocial variables (perceived stress and vulnerability, self-efficacy), as well as health related and demographic variables, on children's current exposure levels. Data were from 135 families whose children (M = 8.6 years old) lived with a smoker and were being treated for cancer. Self-efficacy was the consistent significant psychosocial predictor of exposure and the time since a child's diagnosis was indicative of lower exposure when limiting the sample to only smoking parents (n = 95). Both predictors of exposure have implications on motivation for behavioral change and may be suggestive of a teachable moment. Interventions may profit from tailoring programs to families based on these predictors of exposure, in particular for tobacco-based interventions for parents of medically compromised children, such as children with cancer. PMID- 22308543 TI - The daily patterns of time use for parents of children with complex needs: a systematic review. AB - The aim of this systematic review was to critically examine the research that quantifies and describes the daily patterns of time use by parents of children with complex needs. Four electronic databases were searched. A total of 32 studies (30 peer-reviewed journal articles and two theses) met the inclusion criteria. Three key findings emerged from the review: (a) Parents of children with complex needs carry a significant caregiving burden that often does not reduce as the age of the child increases, (b) supervision or 'vigilance' is a category of childcare that carries a particular time requirement for these parents and (c) parents of children with complex needs spend (sometimes considerable) time undertaking health care-related tasks outside the 'normal' parenting role. The time demands placed on parents caring for a child or children with complex needs at home should be considered when health professionals are negotiating essential and/or additional therapies or treatments to be included in a child's home care regime. PMID- 22308544 TI - An office or a bedroom? Challenges for family-centered care in the pediatric intensive care unit. AB - Although the modern pediatric intensive care unit (PICU) has followed general pediatrics and adopted the family-centered care model, little is known about how families prospectively experience PICU care. The authors' goal was to better understand the experiences of families whose child was hospitalized in a PICU. They conducted a 12-month prospective ethnographic study in a PICU in a tertiary care hospital in a large North American urban center. Data were obtained via participant-observation and formal and informal interviews with 18 families and staff key informants. Findings revealed a disconnect between the espoused model of family-centered care and quotidian professional practices. This divergence emerged in the authors' analysis as a heuristic that contrasts a professional "office" to a sick child's "bedroom." PICU practices and protocols transformed the child into a patient and parents into visitors; issues such as noise, visitation, turf, and privacy could favor staff comfort and convenience over that of the child and family. The authors' discussion highlights suggestions to overcome this divergence in order to truly make the PICU family centered. PMID- 22308545 TI - Supervision to prevent childhood unintentional injury: developmental knowledge and self-efficacy count. AB - Caregiver developmental knowledge was tested as a moderator of the association between caregiver-perceived self-efficacy and perceived supervision to prevent childhood unintentional injury. Caregivers (N = 123; 95 mothers and 28 fathers) of children (M = 3.5 +/- 1.2 years, 49.6% female, 80.8% Caucasian) were recruited from pediatric primary care offices and local message boards. All caregivers completed self-report questionnaires on perceived self-efficacy, developmental knowledge, and perceived supervision to prevent injury. Separate hierarchical linear regression models were conducted to test moderation for mothers and fathers. The interaction effect of perceived self-efficacy and developmental knowledge significantly predicted maternal-perceived supervision, R (2) change = .06, F(1, 86) = 6.76, p < .01. No significant findings were detected for fathers. Models of studying injury prevention that consider complex cognitive-behavioral interactions and their potential modifiable role in the development of injury prevention practices may elucidate upon the attitude-practice gap currently identified in the literature. PMID- 22308546 TI - Changes in the key areas of quality of life associated with age and time since diagnosis of long-term conditions. AB - This study examined whether quality of life areas, that were considered to be important by people with long-term and chronic conditions, altered as a function of their age ('maturational') and time since diagnosis ('adaptational'). Seventy one individuals from two age groups (31-40 and 41-50 years), who had been diagnosed for different lengths of time (<1 year and 10-20 years), creating four groups, were asked to say what quality of life meant to them, and the results were qualitatively analysed. The key theme in determining the quality of life across the entire sample was 'independence and normality' in the participants' lives. However, the other key themes differed across the groups, suggesting that both 'maturation' and 'adaptation' play a role in determining the key areas that people consider, relating to their quality of life. The younger newly diagnosed group made more mention of 'involvement' than the other three groups, all of which mentioned different forms of wellbeing (social-emotional, physical and psychological) as the second most important aspect of their quality of life. These findings have implications for the assessment of quality of life. PMID- 22308547 TI - Reverse D4F, an apolipoprotein-AI mimetic peptide, inhibits atherosclerosis in ApoE-null mice. AB - OBJECTIVE: Synthetic class A amphipathic helical peptide analogs of apolipoprotein-AI (apoAI; with varied phenylalanine residues) are emerging therapeutic approaches under investigation for atherosclerosis. Utilizing retroinverso sequencing, we designed reverse-D4F (Rev-D4F) peptide with 18 d amino acids containing 4 phenylalanine residues and reverse order that allows the side chain residues to be of exact alignment and superimposable to those of the parent l-amino acid peptide. This study examined the effect of Rev-D4F on atherosclerosis in apolipoprotein E (apoE)-null mice and the underlying mechanisms. MATERIALS/METHODS: ApoE-null mice were fed a chow diet and administered water (control), Rev-D4F, or L4F mimetic peptides (0.4 mg/mL, equivalent to 1.6 mg/d) orally in drinking water for 6 weeks. Aortic root atherosclerotic lesion area, lesion macrophage content, and the ability of plasma high-density lipoprotein (HDL) to influence monocyte chemotaxis were measured. RESULTS: Rev-D4F significantly decreased aortic sinus atherosclerotic lesion area and lesion macrophage content without affecting plasma total and HDL-cholesterol levels in apoE-null mice. The HDL from Rev-D4F-treated mice showed enhanced anti inflammatory monocyte chemotactic activity, while low-density lipoprotein (LDL) exhibited reduced proinflammatory activity. In in vitro studies, Rev-D4F inhibited LDL oxidation, endothelial cell vascular cell adhesion molecule 1 (VCAM 1), and monocyte chemotactic factor 1 (MCP-1) expression, and monocyte adhesion to aortic endothelial cells. CONCLUSIONS: The Rev-D4F inhibits atherosclerosis by inhibiting endothelial inflammatory/oxidative events and improving HDL function. The data suggest that Rev-D4F may be an effective apoAI mimetic peptide for further development in preventing atherosclerosis. PMID- 22308548 TI - One step beyond, does rehabilitation influence physical activity? PMID- 22308549 TI - Unravelling self-management for COPD: what next? PMID- 22308550 TI - Factors associated with a shorter time until the next pulmonary exacerbation in adult patients with cystic fibrosis. AB - Time until the subsequent exacerbation (PEx) in cystic fibrosis (CF) is a significant health outcome and one of the significant end points in clinical trials. Risk factors associated with shorter time until the next exacerbation (TUNE) have not been reported. This is a prospective study. TUNE was the number of days from the end of intravenous (IV) antibiotic treatment of a PEx until the day of start of IV antibiotics for the following PEx. Factors assessed were age, gender, site of treatment, CF-related diabetes (CFRD), allergic bronchopulmonary aspergillosis (ABPA) and infection with Pseudomonas aeruginosa (PA). In addition, we examined parameters obtained at day 14 of treatment including forced expiratory volume in the first second (FEV1), body mass index, CF respiratory symptom score, C-reactive protein (CRP) and serum cytokines. A total of 170 exacerbations in 58 adult CF patients (27 female), mean (SD) age 25.8 (6.7) years were analysed. When analysing individual variables, patients with lower FEV1, greater symptom score and higher CRP at the end of exacerbation were associated with shorter TUNE. Patients with ABPA and CFRD had a shorter TUNE than those without. When applying multiple regression analysis, factors associated with shorter TUNE were older age and lower day-14 FEV1 values. Shorter periods until the following PEx are expected in older CF patients and those with lower FEV1 at the end of course of treatment. When these risk factors are present, there may be a justification to take therapeutic steps to increase the time until the following PEx. PMID- 22308551 TI - Self-management programmes for COPD: moving forward. AB - Self-management is of increasing importance in chronic obstructive pulmonary disease (COPD) management. However, there is confusion over what processes are involved, how the value of self-management should be determined, and about the research priorities. To gain more insight into and agreement about the content of programmes, outcomes, and future directions of COPD self-management, a group of interested researchers and physicians, all of whom had previously published on this subject and who had previously collaborated on other projects, convened a workshop. This article summarises their initial findings. Self-management programmes aim at structural behaviour change to sustain treatment effects after programmes have been completed. The programmes should include techniques aimed at behavioural change, be tailored individually, take the patient's perspective into account, and may vary with the course of the patient's disease and co morbidities. Assessment should include process variables. This report is a step towards greater conformity in the field of self-management. To enhance clarity regarding effectiveness, future studies should clearly describe their intervention, be properly designed and powered, and include outcomes that focus more on the acquisition and practice of new skills. In this way more evidence and a better comprehension on self-management programmes will be obtained, and more specific formulation of guidelines on self-management made possible. PMID- 22308552 TI - Palliative care in lung disease. PMID- 22308553 TI - The impact of lung cancer on patients and carers. AB - This article aims to provide a brief review of the literature with regard to the impact of lung cancer on patients and their informal carers. Compared to other types of cancer, the distress associated with lung cancer has been found to be the most intense. Rather than focusing on symptoms in isolation recent emphasis regarding the symptom experience has been on symptoms clusters, as understanding these clusters may improve the management of ongoing and unrelieved symptoms. However, the disparities in methodology are significant barriers to producing comparable results, although recent efforts have been made to address these. Whilst research into symptoms has enormous potential for the management of symptom clusters, it needs to move away from the essentially reductionist stance which currently dominates and broaden its scope to one that acknowledges the complexity of the experience of symptom clusters from the perspective of the patient and their informal carer. Poor management of symptoms complicates patient care and potentially contributes to the heavy burden which often falls on family caregivers, especially as the disease progresses. The majority of studies focus on the experiences of primary care providers, most often the partner/spouse. Such studies have shown that spouses of patients with lung cancer exhibit significant distress and lower levels of quality of life than the general population. Research also indicates that significant others go through a transition process due to changes brought about by the diagnosis of lung cancer and struggle to endure and overcome difficulties and distress. Significant others were seen to suffer during this process of transition and experienced altered relationships. Clinicians working with patients suffering from lung cancer and their carers should intervene to enhance their quality of life from diagnosis, during the disease trajectory and during bereavement. Interventions need to be developed to support both patients and carers. PMID- 22308554 TI - Palliation of dyspnea. PMID- 22308555 TI - Improving the management of dyspnea in the community using rapid learning approaches. AB - Patients with chronic pulmonary disease often suffer from breathlessness or dyspnea. Traditional evidence generation techniques to expand upon current treatment paradigms are limited by the significant delay between study initiation and clinical implementation of findings. Rapid learning health care is a novel approach to health care delivery that relies on intelligent and continuous integration of clinical and research data sets to deliver personalized medicine using the most current evidence available. Results of important studies in the management of chronic respiratory disease are presented in brief; however, the focus of this review is on evidence supporting the implementation of a rapid learning model for symptom management. Recent findings suggest that a rapid learning system is feasible and acceptable to patients with advanced illness, helps monitor symptoms overtime, facilitates study of the impact of novel interventions, and can identify unrecognized needs and concerns. A rapid learning model improves comprehensive assessment, timeliness of intervention, and accrual of contemporaneous data to support best practice that tailors care specific to the needs of patients as their disease and lifestyle change overtime. Using the rapid learning health care model, data collected in the process of routine care can simultaneously function both as clinical information and as a resource for research on patient-centered experiences and outcomes. PMID- 22308556 TI - The interaction of ageing and lung disease. AB - This article explores the structural and physiological changes that occur in the ageing lung, and the impact that lung disease and other co-morbidities may have on it. The major changes associated with ageing are reduced lung elasticity, respiratory muscle strength and chest wall compliance, all of which may be influenced by impaired lung growth in early childhood and adolescence. The resultant reduction in diffusing capacity may not be relevant in a fit older adult, but co-morbidities may interact to cause breathlessness and impairments in quality of life. Lung function declines with age, but forced vital capacity (FVC) begins to decline later than forced expiratory volume in 1 s (FEV(1)) and at a slower rate. This results in a natural fall in the FEV(1)/forced vital capacity (FVC) ratio which may result in overdiagnosis of chronic obstructive pulmonary disease, and hence the need to ensure the FEV(1) is less than 80% before confirming the diagnosis. As older adults probably have a diminished response to hypoxia and hypercapnia, they become more vulnerable to ventilatory failure during high-demand states such as heart failure and pneumonia and therefore to possible poorer outcomes. Poor nutritional status is likely to be an important factor, as is cognitive impairment. It is important to assess older patients using a range of clinical and physiological parameters rather than on the basis of age per se which is a poor predictor of outcome. PMID- 22308557 TI - A prospective, multicentre, randomized, double-blind, placebo-controlled trial of onabotulinumtoxinA to treat plantarflexor/invertor overactivity after stroke. AB - OBJECTIVE: To examine the safety and efficacy of onabotulinumtoxinA (Botox) for plantarflexor overactivity following stroke. DESIGN: Double-blind randomized controlled trial, open-label extension phase. SETTING: Neurology rehabilitation facilities. SUBJECTS: Eighty-five subjects with lower limb hypertonia received 200 U (n = 28) or 300 U (n = 28) of onabotulinumtoxinA or saline (n = 29) injection. PRIMARY MEASURES: Plantarflexor Ashworth scores at 12 weeks post injection and adverse events. Secondary measures: self-reported spasm frequency and pain, physician rating of hypertonia severity, gait quality and active dorsiflexion. RESULTS: Differences were not seen between onabotulinumtoxinA groups; hence data were pooled. Incidence of adverse events was not different between groups (P = 0.61). Reduction in hypertonia was not different between groups at 12 weeks (P = 0.53); however for subjects with Ashworth scores of >3 at baseline, 14/31 in the onabotulinumtoxinA group demonstrated a reduction of >1 grade versus 1/17 receiving placebo injection (P = 0.01). Overall, onabotulinumtoxinA-injected subjects demonstrated significantly greater improvement in spasm frequency (22/54 versus 4/29, P = 0.01), pain reduction (8/54 versus 1/29, P = 0.02), active dorsiflexion (8/54 versus 1/29 P = 0.03) and gait quality (17/54 versus 6/29, P = 0.02) than controls. In the open-label phase, a second onabotulinumtoxinA injection was associated with greater hypertonia reduction (P = 0.005) and gait quality (P = 0.002) compared with single injection. CONCLUSIONS: OnabotulinumtoxinA injection for ankle flexor overactivity after stroke was safe and well tolerated but did not alter local spasticity at 12 weeks; it did reduce spasms and improve gait quality. There were no detectable differences between higher and lower doses. A second injection may be associated with greater change. PMID- 22308558 TI - Functional orthosis in shoulder joint subluxation after ischaemic brain stroke to avoid post-hemiplegic shoulder-hand syndrome: a randomized clinical trial. AB - OBJECTIVE: To examine whether the use of a shoulder joint functional orthosis over four weeks can mitigate the development or progression of the shoulder-hand syndrome in patients with shoulder joint subluxation after stroke. DESIGN: Two armed randomized controlled trial. SETTING: Rehabilitation unit of a neurological hospital, single centre. SUBJECTS: Forty-one patients with caudal subluxation of the glenohumeral joint and hemiparesis of the upper extremity after ischaemic brain stroke. INTERVENTIONS: Support by functional orthosis Neuro-Lux (Sporlastic, Nurtingen, Germany) on top of usual care according to current guidelines (experimental, n = 20) versus usual care alone (control, n = 21). MAIN MEASURES: Weekly shoulder-hand syndrome scores (severity of clinical symptoms ranging from 0 to 14), discomfort caused by the orthosis, and its usage rate. The primary outcome was the average shoulder-hand syndrome score on days 14, 21 and 28, adjusted for the baseline shoulder-hand syndrome score. RESULTS: The adjusted mean shoulder-hand syndrome score was lower by 3.1 in the intervention compared to the control subjects (95% confidence interval 1.9 to 4.3, P < 0.0001). Marginal or no discomfort from treatment with the orthosis was reported in 15 patients (75%), and only a single patient (5%) felt severe discomfort during the entire treatment. Use of the orthosis during the prescribed time was 89%. CONCLUSIONS: The orthosis examined in this trial has been successfully shown to reduce and prevent the development of clinical symptoms of shoulder-hand syndrome. Timing and duration of application of the orthosis as well as its combination with other therapeutic measures should be investigated in future clinical trials. PMID- 22308559 TI - Differential effects of rhythmic auditory stimulation and neurodevelopmental treatment/Bobath on gait patterns in adults with cerebral palsy: a randomized controlled trial. AB - OBJECTIVES: To investigate the effects of rhythmic auditory stimulation (RAS) on gait patterns in comparison with changes after neurodevelopmental treatment (NDT/Bobath) in adults with cerebral palsy. DESIGN: A repeated-measures analysis between the pretreatment and posttreatment tests and a comparison study between groups. SETTING: Human gait analysis laboratory. SUBJECTS: Twenty-eight cerebral palsy patients with bilateral spasticity participated in this study. The subjects were randomly allocated to either neurodevelopmental treatment (n = 13) or rhythmic auditory stimulation (n = 15). INTERVENTIONS: Gait training with rhythmic auditory stimulation or neurodevelopmental treatment was performed three sessions per week for three weeks. Temporal and kinematic data were analysed before and after the intervention. Rhythmic auditory stimulation was provided using a combination of a metronome beat set to the individual's cadence and rhythmic cueing from a live keyboard, while neurodevelopmental treatment was implemented following the traditional method. MAIN MEASURES: Temporal data, kinematic parameters and gait deviation index as a measure of overall gait pathology were assessed. RESULTS: Temporal gait measures revealed that rhythmic auditory stimulation significantly increased cadence, walking velocity, stride length, and step length (P < 0.05). Kinematic data demonstrated that anterior tilt of the pelvis and hip flexion during a gait cycle was significantly ameliorated after rhythmic auditory stimulation (P < 0.05). Gait deviation index also showed modest improvement in cerebral palsy patients treated with rhythmic auditory stimulation (P < 0.05). However, neurodevelopmental treatment showed that internal and external rotations of hip joints were significantly improved, whereas rhythmic auditory stimulation showed aggravated maximal internal rotation in the transverse plane (P < 0.05). CONCLUSIONS: Gait training with rhythmic auditory stimulation or neurodevelopmental treatment elicited differential effects on gait patterns in adults with cerebral palsy. PMID- 22308560 TI - Efficacy and cost-effectiveness of an automated screening algorithm in an inpatient clinical trial. AB - INTRODUCTION: Screening and recruitment for clinical trials can be costly and time-consuming. Inpatient trials present additional challenges because enrollment is time sensitive based on length of stay. We hypothesized that using an automated prescreening algorithm to identify eligible subjects would increase screening efficiency and enrollment and be cost-effective compared to manual review of a daily admission list. METHODS: Using a before-and-after design, we compared time spent screening, number of patients screened, enrollment rate, and cost-effectiveness of each screening method in an inpatient diabetes trial conducted at Massachusetts General Hospital. Manual chart review (CR) involved reviewing a daily list of admitted patients to identify eligible subjects. The automated prescreening (APS) method used an algorithm to generate a daily list of patients with glucose levels >= 180 mg/dL, an insulin order, and/or admission diagnosis of diabetes mellitus. The census generated was then manually screened to confirm eligibility and eliminate patients who met our exclusion criteria. We determined rates of screening and enrollment and cost-effectiveness of each method based on study sample size. RESULTS: Total screening time (prescreening and screening) decreased from 4 to 2 h, allowing subjects to be approached earlier in the course of the hospital stay. The average number of patients prescreened per day increased from 13 +/- 4 to 30 +/- 16 (P < 0.0001). Rate of enrollment increased from 0.17 to 0.32 patients per screening day. Developing the computer algorithm added a fixed cost of US$3000 to the study. Based on our screening and enrollment rates, the algorithm was cost-neutral after enrolling 12 patients. Larger sample sizes further favored screening with an algorithm. By contrast, higher recruitment rates favored individual CR. LIMITATIONS: Because of the before-and-after design of this study, it is possible that unmeasured factors contributed to increased enrollment. CONCLUSION: Using a computer algorithm to identify eligible patients for a clinical trial in the inpatient setting increased the number of patients screened and enrolled, decreased the time required to enroll them, and was less expensive. Upfront investment in developing a computerized algorithm to improve screening may be cost-effective even for relatively small trials, especially when the recruitment rate is expected to be low. PMID- 22308561 TI - A controlled trial of a cognitive skills program for personality-disordered offenders. AB - OBJECTIVE: There is a need to find effective treatments for individuals with antisocial and borderline personality disorder who are known to be difficult to engage and treat. Many of these individuals share considerable overlap with symptoms of ADHD, hence this study aimed to evaluate the Reasoning and Rehabilitation ADHD program (R&R2 ADHD) among patients with severe personality disorder. METHOD: A total of 31 males detained in a "dangerous and severe personality disorder" unit completed questionnaires at baseline and post treatment to assess social problem solving, violent attitudes, anger, ADHD symptoms, emotional control, and social functioning. A total of 16 patients participated in the group condition, and their scores were compared with 15 waiting-list controls who received treatment as usual. RESULTS: In all, 76% of group participants completed the program. In contrast to controls, they showed significant improvements in scores with mainly medium effect sizes. CONCLUSION: R&R2 ADHD was effective in a small sample of severely personality-disordered offenders. PMID- 22308563 TI - Vasomotor symptoms and negative affect. PMID- 22308562 TI - Postmenopausal hormone therapy and coronary artery atherosclerosis. PMID- 22308564 TI - Effects of weight changes on the bone. PMID- 22308565 TI - Stopping HRT: were women ill advised? PMID- 22308566 TI - Adherence to osteoporosis medications. PMID- 22308567 TI - Barriers to service provision. Introduction. PMID- 22308568 TI - Unilateral bubbly cystic brain lesions on MRI. PMID- 22308569 TI - A woman with headaches and blurred vision. PMID- 22308570 TI - Retraction notice to "Prostate cancer screening in the Tyrol, Austria: experience and results" [Eur J Cancer 36 (2000) 1322-1335]. PMID- 22308571 TI - Hip disease in cerebral palsy. PMID- 22308572 TI - Successful surgical treatment of entrapped thrombus in patent foramen ovale. PMID- 22308573 TI - The unnerving dilemma: understanding trigeminal neuralgia. PMID- 22308574 TI - Reconsidering conventional wisdom: new case brings old question to forefront. PMID- 22308575 TI - Who is the oral and maxillofacial surgeon? PMID- 22308576 TI - SCORE at Maine Medical Center. PMID- 22308577 TI - [A case of anstomotic stricture after esophagectomy sufficiently treated by endoscopic triamcinolone injection therapy]. AB - We report a case of 50-year-old man with refractory anastomotic stricture after esophagectomy, which was successfully treated with endoscopic triamcinolone injection therapy. He received a curative operation for advanced thoratic esophageal carcinoma (Mt, Type 3, cT3, cN1, MO, Stage III). Anastomotic leakage was occurred as post-operative adverse event, which recovered conservatively, and subsequently resulted in refractory anastomotic stricture. He had a recurrence of dysphagia despite of repeated bougienage and endoscopic balloon dilatation. Four years later, he received an intralesional triamcinolone injection in anastomotic stricture every four weeks. According to the 5 courses of treatment, anastomotic stricture was cured and there was no recurrence confirmed. Intralesional triamcinolone injection may be one of the promising options for the treatment of refractory anastomotic stricture after esophagectomy. PMID- 22308578 TI - Canadian Association of Gastroenterology consensus guidelines on safety and quality indicators in endoscopy. AB - BACKGROUND: Increasing use of gastrointestinal endoscopy, particularly for colorectal cancer screening, and increasing emphasis on health care quality, highlight the need for clearly defined, evidence-based processes to support quality improvement in endoscopy. OBJECTIVE: To identify processes and indicators of quality and safety relevant to high-quality endoscopy service delivery. METHODS: A multidisciplinary group of 35 voting participants developed recommendation statements and performance indicators. Systematic literature searches generated 50 initial statements that were revised iteratively following a modified Delphi approach using a web-based evaluation and voting tool. Statement development and evidence evaluation followed the AGREE (Appraisal of Guidelines, REsearch and Evaluation) and GRADE (Grading of Recommendations, Assessment, Development and Evaluation) guidelines. At the consensus conference, participants voted anonymously on all statements using a 6-point scale. Subsequent web-based voting evaluated recommendations for specific, individual quality indicators, safety indicators and mandatory endoscopy reporting fields. Consensus was defined a priori as agreement by 80% of participants. RESULTS: Consensus was reached on 23 recommendation statements addressing the following: ethics (statement 1: agreement 100%), facility standards and policies (statements 2 to 9: 90% to 100%), quality assurance (statements 10 to 13: 94% to 100%), training, education, competency and privileges (statements 14 to 19: 97% to 100%), endoscopy reporting standards (statements 20 and 21: 97% to 100%) and patient perceptions (statements 22 and 23: 100%). Additionally, 18 quality indicators (agreement 83% to 100%), 20 safety indicators (agreement 77% to 100%) and 23 recommended endoscopy-reporting elements (agreement 91% to 100%) were identified. DISCUSSION: The consensus process identified a clear need for high quality clinical and outcomes research to support quality improvement in the delivery of endoscopy services. CONCLUSIONS: The guidelines support quality improvement in endoscopy by providing explicit recommendations on systematic monitoring, assessment and modification of endoscopy service delivery to yield benefits for all patients affected by the practice of gastrointestinal endoscopy. PMID- 22308579 TI - A qualitative study of pandemic influenza preparedness among small and medium sized businesses in New York City. AB - Small businesses need to engage in continuity planning to assure delivery of goods and services and to sustain the economy during an influenza pandemic. This is especially true in New York City, where 98 per cent of businesses have fewer than 100 employees. It was an objective therefore, to determine pandemic influenza business continuity practices and strategies suitable for small and medium-sized NYC businesses. The study design used focus groups, and the participants were owners and managers of businesses with fewer than 500 employees in New York City. The main outcome measures looked for were the degree of pandemic preparedness, and the feasibility of currently proposed business continuity strategies. Most participants reported that their businesses had no pandemic influenza plan. Agreement with feasibility of specific business continuity strategies was influenced by the type of business represented, cost of the strategy, and business size. It was concluded that recommendations for pandemic-related business continuity plans for small and medium-sized businesses should be tailored to the type and size of business and should highlight the broad utility of the proposed strategies to address a range of business stressors. PMID- 22308580 TI - Schistosomiasis: population requiring preventive chemotherapy and number of people treated in 2010. PMID- 22308581 TI - Progress in global measles control, 2000-2010. PMID- 22308582 TI - [Failed puncture of the jugular vein. The patient's neck swelled up]. PMID- 22308583 TI - [Endocrine emergencies. What should be done immediately so the patient survives the crisis]. PMID- 22308584 TI - [Secondary coronary heart disease prevention. Will CEPT inhibitors be the next breakthrough?]. PMID- 22308585 TI - [Symptomatic coronary heart disease. Impressive plaque reduction with high dose statins]. PMID- 22308586 TI - [FAQs in chronic inflammatory bowel diseases. This way your patient stays in remission]. PMID- 22308587 TI - [Pericarditis in an athlete. How long must he abstain from sports?]. PMID- 22308588 TI - [Inguinal hernia]. PMID- 22308589 TI - [Diagnosis of inguinal hernia]. PMID- 22308590 TI - [Surgical options for inguinal hernia repair]. PMID- 22308591 TI - [Post-operative care after inguinal hernia repair]. PMID- 22308592 TI - [Dupuytren contracture]. PMID- 22308593 TI - [High blood pressure in the morning]. PMID- 22308594 TI - [German national disease management guidelines "diabetic neuropathy". Important implications on clinical practice]. PMID- 22308595 TI - [Drug-induced analgesia. Etiology oriented pain therapy]. PMID- 22308596 TI - ANA to comment on new rules on accountable care organizations. PMID- 22308597 TI - Advocacy at the state level: why it's important. PMID- 22308598 TI - Creating avenues to nursing excellence. PMID- 22308599 TI - C. diff stinks! A proposed screening too. PMID- 22308601 TI - Joplin has health care at fingertips. PMID- 22308600 TI - Core values in action. A Joplin nurse's story. PMID- 22308602 TI - Speaking up for those who can't. PMID- 22308603 TI - The spousal IRA rule. PMID- 22308604 TI - The 90-10 health care cost issue. PMID- 22308605 TI - Part 1: knowledge and educational experience. AB - PURPOSE: The purpose of this study was to determine the current knowledge and educational experiences of Massachusetts dentists regarding child maltreatment and to compare those findings to a similar survey completed in 1975. METHODS: A web-based questionnaire was emailed to 3,451 members of the Massachusetts Dental Society. The questionnaire was divided into three parts: demographic information on the dentists and their practices; knowledge and reporting behaviors of child maltreatment; and educational experiences with child maltreatment. RESULTS: The response rate to the survey was 19.6 percent, with 678 dentists completing the questionnaire. Ninety percent of the dentists were aware of their legal obligation to report cases of child maltreatment, and 66.5 percent were able to name the appropriate agency for reporting such cases, both of which were significant and large increases since the 1975 survey. The most common source of child maltreatment education was from the dental literature, followed by predoctoral education and continuing education. Seventy-four percent of the responding dentists were comfortable in reporting cases of child maltreatment; however, 51 percent felt that they needed further education on child maltreatment. CONCLUSIONS: The majority of responding Massachusetts dentists were aware of their legal obligation to report cases of child maltreatment and where to do so, which is a significant and large improvement since the 1975 survey. PMID- 22308606 TI - Part 2: abuse. AB - PURPOSE: The purpose of this study was to identify the current rate of observing and reporting of child abuse among Massachusetts dentists, determine if there have been changes since a similar 1975 survey, and review possible factors associated with child abuse observation and reporting behaviors. METHODS: A web based questionnaire was emailed to 3,451 members of the Massachusetts Dental Society (MDS). The questionnaire was divided into three parts: demographic information on the dentists and their practices; knowledge and reporting behaviors of child maltreatment; and educational experiences with child maltreatment. RESULTS: The response rate to the survey was 19.6 percent, with 678 dentists completing the questionnaire. In the year prior to taking the survey, the responding dentists encountered 93 cases suspicious of child abuse, of which 35 cases were considered to be definitive child abuse. Twenty-two percent of the suspicious cases were reported to authorities. Forty-three percent of the definitive cases were reported, which was a significant increase when compared to the 1975 survey. Fewer dentists were seeing and reporting both suspicious and definitive cases of abuse when compared to the 1975 findings, but this may have been the result of the differences in the specialty composition of the two survey samples. CONCLUSIONS: Massachusetts dentists continue to see and report cases of child abuse, but fall short of the legal requirement to report all suspicious or definitive cases. However, when compared to the 1975 survey, a greater percentage of dentists reported cases of child abuse that they believed to be definitive. PMID- 22308607 TI - Part 3: neglect. AB - PURPOSE: The purpose of this study was to determine the current rate of observing and reporting of child neglect among Massachusetts dentists and to identify possible factors associated with child neglect observation and reporting behaviors. METHODS: A web-based questionnaire was emailed to 3,451 members of the Massachusetts Dental Society (MDS). The questionnaire was divided into three parts: demographic information on the dentists and their practices; knowledge and reporting behaviors of child maltreatment; and educational experiences with child maltreatment. RESULTS: The response rate to the survey was 19.6 percent, with 678 dentists completing the questionnaire. In the year prior to taking the survey, the responding dentists encountered 239 cases of child neglect, of which 20 percent were reported to authorities. The most powerful predictor for seeing and reporting cases of child neglect was the dentist's participation in child maltreatment continuing education courses. CONCLUSIONS: Massachusetts dentists do see and report cases of child neglect; however, only a minority of these cases was reported. Participation in continuing education courses was a strong predictor of dentists' both seeing and reporting cases of child neglect. PMID- 22308608 TI - The dental team's role in identifying and reporting cases of child abuse. PMID- 22308609 TI - Dentistry: The first line of defense against domestic violence. PMID- 22308610 TI - Ridge preservation and advanced bone grafting for the general practitioner. PMID- 22308611 TI - A clinico-pathologic correlation. PMID- 22308612 TI - Poorly healing extraction socket. PMID- 22308613 TI - For goodness' sake. PMID- 22308614 TI - Current concepts of articular cartilage repair. AB - Articular cartilage provides a vital function in the homeostasis of the joint environment. It possesses unique mechanical properties, allowing for the maintenance of almost frictionless motion over a lifetime. However, cartilage is vulnerable to traumatic injury and due to its poor vascularity and inability to access mesenchymal stem cells, unable to facilitate a satisfactory healing response. Untreated chondral defects are thus likely to predispose patients to the development of osteoarthritis. Reconstitution and repair of articular cartilage is dependent on the neosynthesis or implantation of cartilage matrix elements, a goal which can be achieved through a variety of surgical means. Commonly used repair techniques include marrow stimulation, structural osteo articular autografts or chondrocyte implantation. Despite substantial differences in the complexity and technical application of each method, all are united in the endeavour to restore joint function and prevent joint degeneration. Anyone attempting to treat cartilage defects must possess a basic understanding of the physiology of cartilage growth, and relevant factors affecting cartilage healing and repair. Furthermore, knowledge of the biomechanics and kinematics of the knee are essential in order to appreciate the forces acting on joint surfaces and repair tissues. Although clinical success is dependent on appropriate patient selection, accurate clinical assessment, definition of root causes and application of the right choice of treatment modality, the ultimate outcome of any intervention remains heavily reliant on the surgeon's proficiency in the technical aspects of the chosen surgical procedure. PMID- 22308615 TI - Double semi-tubular plating of clavicle using a piggyback technique--an alternative way of treating clavicle mid-shaft fractures in young patients. AB - The majority of clavicle fractures unite uneventfully. Indications for operative surgery are limited, with high rates of complications. We describe our results with an alternative cost effective method of treating these injuries in young patients. It is a retrospective series of 20 patients treated between January 2005 and January 2009 with a "piggy back" technique using double plating with two 3.5 mm drill hole semitubular plates. All patients were assessed with DASH (Disability of Arm, Shoulder and Hand) score at last review. Average time to union was 12.5 weeks. The average DASH score was 834 (0-34.2). There was one case each of non-union, implant removal and symptomatic numbness around the scar. The overall complication rate was 15% with 5% incidence of non-union. The results compare favourably with previously published series. We propose that this technique allows a cost effective way of treating these fractures in young patients, with a high patient satisfaction rate. PMID- 22308616 TI - The role of acromion morphology in chronic subacromial impingement syndrome. AB - This study investigated the role of acromion morphology in the aetiology of chronic subacromial impingement syndrome. Forty five patients with chronic subacromial impingement syndrome were included in the study. They were distributed into three groups according to their acromion types: six (13.3%) patients had type 1, 24 (533%) patients type 2 and 15 (333%) patients type 3 acromion. Constant scoring was used for clinical evaluation. Arthroscopic subacromial decompression was performed in all patients in the three groups, without performing any acromioplasty that would change the morphology of acromion. We then compared the average Constant scores changes in all three groups after arthroscopic subacromial decompression. The average follow-up was 28.6 months (range: 12-47). The average change in Constant score after arthroscopic subacromial decompression was 5830 in patients with type 1 acromion, 58.21 in those with type 2 and 54.07 in those with type 3. No significant difference was observed between the changes in the average Constant scores of the three groups (p > 0.005). The scores were significantly improved following arthroscopic subacromial decompression in all three groups (p < 0.005).In this study, acromion type was not found to have an important role in the aetiology of chronic impingement syndrome; arthroscopic subacromial decompression without simultaneous acromioplasty thus appears as an appropriate treatment. PMID- 22308617 TI - Return to work after arthroscopic subacromial decompression. AB - The incidence of arthroscopic subacromial decompression has been increasing over the last few years. Little is known about the duration of sick leave after such a procedure. The aim of this study was to determine the time till return to full duty and to explore the various influencing factors. We retrospectively evaluated a group of 166 patients who consecutively underwent arthroscopic subacromial decompression for subacromial impingement syndrome. One hundred patients were professionally active at the time of surgery; the mean duration till return to full duty was 11.1 weeks. Self-employed workers had the shortest sick leave period (median time of 1 week). No statistically significant difference was seen between the group with a financial compensation from the national health insurance system (median time of 12 weeks) and the group with income replacement by a private insurance company (median time of 8 weeks). Patients performing manual labour typically had a longer period of sick leave than other employees (12 versus 8 weeks). A longer absence from work was also observed in individuals who underwent a concomitant arthroscopic AC resection and patients with a higher BMI. PMID- 22308618 TI - Outcome of arthroscopic rotator cuff repair in large tears: the exposed footprint. AB - The purpose of this retrospective study was to evaluate the clinical results of arthroscopic single-row repair in large rotator cuff tears. Selection was based on the extent of the "exposed footprint" (EFP) obtained by adding up the width of the subscapularis tear and the width of the supra/infraspinatus tear. Three groups were studied: Type I had an EFP of less than 5 cm; Type II had an EFP of 5 cm or more; tears allowing only partial repair were studied separately. During a period of nearly three years (in 2002-04) 49 shoulders complied with our selection. There were 25 type I and 24 type II tears. Subscapularis tears were found in 32/49 shoulders (65%); 10 shoulders (20%) had only partial repair. At an average follow-up of 33 months, all patients were subjected to an outcome assessment using the VAS, the Simple Shoulder Test (SST), Constant score (CS) and strength measurement. A near normal shoulder function (11-12 Yes-answers in the SST) was obtained in 68% of the patients with type I tears, compared to 33% of type II tears (p = 0.02). The adjusted CS for patients with a type I tear was 88%, compared to 77% for patients with a type II (p = 0.01); strength was 69% for type I and 36% for type II shoulders (p = 0.001). After arthroscopic single-row and margin-convergence repair, a near normal shoulder function was obtained in two-thirds of the shoulders with an EFP of up to 5 cm. When the EFP was larger, this outcome was achieved in only one-third of the shoulders. PMID- 22308619 TI - Comparison between two classifications of humeral head fractures: Neer and AO ASIF. AB - Our purpose was to verify if the Neer and AO-ASIF classifications for fractures of the proximal humerus satisfy the requisites of simplicity and reproducibility and if the parameters that they consider to establish the severity of the fracture are similar. Two of the authors classified the proximal humeral fractures of 227 patients based on plain radiographs, and they repeated the classification five years later. The reliability, reproducibility and coherence of the classifications were investigated. Inter-observer reliability was K = 0.77 (Neer) and K = 0.65 (AO-ASIF) while intra-observer reproducibility was K = 0.68 (examiner I) and K = 0.63 (examiner II). In 1/5 of the cases, disagreement led to a different classification of the same fracture. Furthermore, neither classification establishes a linear scale of gravity able to provide an indication for treatment. The Neer and AO-ASIF classifications have a low reproducibility and reliability when fractures, especially those with 3 or 4 parts, are assessed by means of plain radiographs. Therefore, patients with complex fractures should be submitted to CT to have a correct pre-operative diagnosis. PMID- 22308620 TI - Elbow arthrolysis for traumatic arthrofibrosis: a shift towards minimally invasive surgery. AB - The elbow joint needs to be both mobile and stable to exercise its hinge function, which is the key to a normal upper limb. Loss of motion in the elbow joint leads to an exponential functional handicap. Elbow trauma is a common cause of elbow stiffness. Open elbow arthrolysis with release of the capsule has been demonstrated to be a very useful treatment. Arthroscopic elbow arthrolysis has now gained popularity, along with the rapid evolution in elbow arthroscopy. The authors present the preliminary results of this technique in 12 patients, with a mean follow-up of 19.4 months. The range of motion significantly increased from an extension lag of 39.2 degrees and a flexion limited to 115 degrees to an extension lag of 17.9 degrees and a flexion of 131.7 degrees. On average, a 38 degrees gain in range of motion was achieved. This result is comparable with a gain of 40 degrees after open arthrolysis, reported by the senior author in a previous study. The DASH score improved from 39 to 28, but not significantly, and the VAS for pain from 5.5 to 3.4 (significantly). All patients would undergo the procedure again and they experienced a mean subjective improvement of 63.6%. A literature review showed that open and arthroscopic arthrolysis yield a gain of about 44.10 degrees and 31.25 degrees, respectively. The conclusion is that there certainly is a place for arthroscopic elbow arthrolysis. PMID- 22308621 TI - Proximal row carpectomy for chronic unreduced perilunate dislocations. AB - We evaluated the results of proximal row carpectomy (PRC) for unreduced perilunate dislocation in 6 patients. The average period from the injury to the operation was 24 weeks. The modified Mayo wrist score was used for clinical evaluation. Radiological evaluation was based on the radius-capitate alignment. Pain disappeared in 4 cases; mild pain during activity persisted in 2 cases. The average flexion-extension are was 59% of the values on the unaffected side. The average grip strength was 72% of the unaffected side, and the average modified Mayo wrist score was 71 points. Three patients showed favourable radius-capitate alignment, while the other 3 patients showed poor radius-capitate alignment on the radiographs. The postoperative radius-capitate alignment was related to the preoperative position of the capitate on the lateral view. Those with poor radius capitate alignment tended to obtain lower scores compared to those with favourable alignment. PMID- 22308622 TI - Clinical and functional outcome of the Birmingham hip resurfacing. AB - The Birmingham hip resurfacing (BHR) arthroplasty has shown good medium-term results in the centres that have been involved in its development. A retrospective cohort study analyzing the clinical and functional outcome of 297 metal-on-metal BHR arthroplasties at an independent hospital was performed. At medium-term follow-up, 4 patients had died, 8 patients were lost to follow-up (2.7%), and 6 hips (2.0%) had undergone revision surgery. The mean Harris hip score (HHS) increased from 56.2 preoperatively to 96.4 at follow-up. The BHR resulted in a very high postoperative HHS and enabled active patients to return to work and engage in sports. With an acceptable revision rate of 2.0% and an overall survival rate of 97.1% at five years, our results were similar to those of the designer centers. PMID- 22308623 TI - Metal ion levels decrease after revision for metallosis arising from large diameter metal-on-metal hip arthroplasty. AB - Concerns have been renewed regarding the possible long-term effects of elevated circulating levels of cobalt and chromium as a direct result of implantation of large femoral head diameter metal-on-metal bearings. In order to establish whether metal ion levels remain persistently elevated, we compared metal ion levels before and after revision surgery in patients with large head diameter (greater than 38 mm) metal-on-metal total hip arthroplasty or hip resurfacing arthroplasty. At greater than one year post removal of a large-diameter metal-on metal hip implant for the indication of symptomatic metallosis, metal ion levels were found to fall to almost normal levels. PMID- 22308624 TI - Leg length discrepancy following femoral shaft fracture in children: clinical considerations and recommendations. AB - Femoral shaft fracture in children is a frequently encountered problem. Residual leg length discrepancy persisting at skeletal maturity is the most common complication. In this study, a positive correlation was found between the amount of bone fragments overlap and the overgrowth phenomenon. When comparing final leg length discrepancy with initial fragments overlap, 9.3 mm was found to be the maximal overlap to be tolerated in order to avoid significant leg length discrepancy. PMID- 22308625 TI - Promises and difficulties with the use of femoral intra-medullary lengthening nails to treat limb length discrepancies. AB - Limb lengthening using external fixation may be associated with problems such as pin-track infections, poor patient acceptance, muscle transfixation, secondary axial deformity and re-fractures. Intramedullary lengthening nails have been designed to address these issues. We present our results for femoral limb lengthening in adults managed by intramedullary lengthening nails. A retrospective review was undertaken for 8 femoral lengthening procedures performed in adults using intra-medullary lengthening nails over a three-year period. The average age of our patients was 34 years; the average duration of follow-up was 26.5 months (range: 8 to 40 months). An Albizzia nail was used in 5 procedures, an Intra-medullary Skeletal Kinetic Distractor (ISKD nail) in 3 procedures. Target lengthening was achieved in 6 out of 8 femurs with an average of 38.77 mm (range: 0 to 70 mm) length gained. The distraction index (length gained per day) was 0.58 on average (range: 0-1.25) and the consolidation index average was 5039 (range: 0-79) days/cm. Premature consolidation was noted in 4 cases, runaway acute lengthening in one patient; prominent metalwork--noted in 4 patients--and a bent nail were frequent obstacles and meant multiple visits to theatre. Femoral lengthening with an intramedullary lengthening nail is a reasonable alternative to external fixators, thereby avoiding problems associated with callotasis using external fixation methods. It is however, important to counsel patients regarding possibilities of significant obstacles including failure and multiple visits to theatre during the process. PMID- 22308626 TI - Malignant proximal fibular tumours: a case series of 17 patients. AB - The aim of this study was to establish whether the proximity of significant neurovascular structures around the surgical excision results in higher rates of recurrence and poorer survival outcomes. A retrospective study of all patients treated at a regional bone tumour unit for proximal fibula Ewing's tumours and osteosarcomas was conducted, and in total 17 patients were identified. The recurrence rate of all cases was 29.4% and the overall 5 year survival was 70.5%. The recurrence rate just for osteosarcoma was 50%, which compared poorly to published recurrence rates throughout the appendicular skeleton. The 5-year survival for proximal fibula osteosarcoma of 50% was also worse than generalised survivorship data reported in non-metastatic osteosarcoma. This series demonstrates that malignant proximal fibula tumours are a difficult entity to manage and recurrence rates and patient survival are poor for osteosarcoma. PMID- 22308627 TI - The percutaneous use of a pointed reduction clamp during intramedullary nailing of distal third tibial shaft fractures. AB - The purpose of this retrospective chart and radiographic review is to describe an effective reduction technique during intramedullary nailing of distal metaphyseal tibia fractures with the use of a pointed percutaneous clamp. Between 2007 and 2010, 100 patients who sustained 102 tibia fractures were definitively treated with an intramedullary nail at one of two medical centers. Diaphyseal fractures and injuries with an associated disruption of the distal tibiofibular joint were excluded from our study. A total of 27 patients with 27 distal metaphyseal tibia fractures (OTA types 42-A, 43-A, and 43-B) were included. All 27 patients underwent IM nailing of their fractures with anatomic reduction achieved using a percutaneously placed pointed reduction clamp prior to insertion of the IM implant. Fracture alignment and angular deformity was assessed using goniometric measurement functions on the PACS system (GE, Waukeshau, WI) obtained from preoperative and postoperative anteroposterior and lateral images for all subjects. Malalignment was defined as more than 5 degrees of angulation in any plane. Fourteen of the fractures were classified as OTA 42-A, 9 were OTA 43-A, and 4 were OTA 43-B. Analysis of post-closed reduction, preoperative anteroposterior radiographs revealed a mean of 7.9 degrees of coronal plane (range: 0.9 degrees-26 degrees) angulation. Post closed reduction preoperative lateral radiographs revealed a mean of 6.8 degrees sagittal plane (range: 0 degrees-24.6 degrees) angulation. Postoperative anteroposterior and lateral radiographs showed the distal segment returned to its anatomical alignment with a mean angulation of 0.5 degrees (range, 0 degrees-3.5 degrees) and 0.7 degrees (range, 0 degrees-4.2 degrees) of varus/ valgus and apex anterior/posterior angulation, respectively. These results showed an acceptable postopertative alignment in all 27 distal third fractures. No intra-operative or postoperative complications were noted in the study group. This study suggests that the use of percutaneous clamps during intramedullary nailing of distal metaphyseal tibia fractures is an easily-reproducible and effective method of reduction with no associated intraoperative complications. PMID- 22308628 TI - Clinical and radiographic results after treatment of cervical degenerative disc disease with the bryan disc prosthesis: a prospective study with 2-year follow up. AB - The purpose of this study was to prospectively evaluate the clinical and radiographic results obtained with the Bryan disc prosthesis (Medtronic Sofamor Danek, Memphis, TN) in 20 consecutive patients with single-level or two-level cervical degenerative disc disease. All patients were followed up for at least two years. The mean Neck Disability Index and the visual analogue scale for neck and arm pain scores were significantly reduced for all postoperative periods compared with the mean preoperative values. SF-36 outcome measures, including the physical and mental component scores, significantly improved after surgery and remained unchanged or improved at two years postoperatively. According to Odom's scale, 18 patients (90%) had good to excellent outcomes. The range of movement of the cervical spine, of the functional spinal unit, the treated segment and the adjacent segment temporarily decreased at the early assessment, but all recovered to preoperative levels over a 6-24 months time period. There was no heterotopic ossification at the implanted levels, no adjacent level degeneration and no prosthesis subsidence or excursion. Cervical disc replacement using the Bryan disc prosthesis appeared to be safe and demonstrated encouraging clinical and radiological outcomes. However, further studies are required to assess the long term efficacy of this prosthesis and its protective influence on adjacent levels. PMID- 22308629 TI - Single-stage posterior debridement and single-level instrumented fusion for spontaneous infectious spondylodiscitis of the lumbar spine. AB - Spontaneous infectious spondylodiscitis (SIS) is an uncommon condition. The purpose of this retrospective study of 10 adult patients (6 males and 4 females, average age 52 years), all with lumbar SIS and epidural abscess, was to analyze the efficacy of single-stage posterior debridement plus single-level interbody grafting with autologous bone, and transpedicular screw-rod instrumentation. The mean follow-up period was 43 months, with a minimum of 30 months. The back pain was relieved within 3 to 8 days after surgery. Neurologic deficits, present in 5 cases, all improved. Solid fusion was achieved at 6 months in all 10 cases. The mean VAS for pain improved from 7.5 to 1.6, the mean Oswestry Disability Index from 57.8% to 8.1%. The mean physical component of SF-36 (PCS) improved from 32.4% to 54.7%, the mean mental component of SF-36 (MCS) improved from 33.8% to 57.2%. All these changes were significant (p < 0.001). No recurrence of infection was noted. The outcome was quite satisfactory in terms of fusion rate and quality of life. PMID- 22308630 TI - Methotrexate and post operative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery--a ten year follow-up. AB - In the 1990's there were concerns that methotrexate might increase the risk of post operative complications following elective orthopaedic surgery; as a result many Units initiated policies to discontinue methotrexate prior to elective orthopaedic surgery. In 2001 we carried out a controlled study of complications after elective surgery in rheumatoid arthritis (RA) patients who either continued or discontinued methotrexate prior to surgery. In this study we showed that continuation of methotrexate therapy prior to orthopaedic surgery did not increase the risk of infection or surgical complication occurring in patients with RA within one year of surgery. The limitation of this study was that complications later than one year were not studied. Sixty-five patients have been followed up. Thirty-one were fully assessed in clinic and 34 underwent a structured telephone interview. There were no incidences of deep bone infection in any patient group so that there is no evidence that continued methotrexate therapy in the perioperative period increases the risk of late deep infections. We adhere to our original advice that in the absence of renal failure or sepsis, methotrexate therapy should not be stopped before elective orthopaedic surgery in patients with RA whose disease is controlled by the drug before surgery. PMID- 22308631 TI - Radiofrequency ablation of osteoid osteomas: five years experience. AB - The purpose of this study is to retrospectively evaluate the efficacy of radiofrequency ablation as a curative treatment method for benign bone tumours. Twenty-nine osteoid osteomas were treated with radiofrequency ablation. Primary success rate was 89.6% and total secondary success rate was 93.1%. Mean clinical follow-up period was 26.7 months (range: 6-63 months). Statistical analysis of 25 cases of osteoid osteomas with CT follow-up revealed that post-treatment re ossification does not correlate with clinical outcome (p = 0.14) but is strongly correlated with long-term (> or = 12 months) CT follow-up (p = 0.014). Percutaneous radiofrequency ablation was found to be an effective and safe treatment for osteoid osteomas. CT findings cannot solely differentiate between treatment successes and failures. PMID- 22308632 TI - Insertion of intramedullary nails from the suprapatellar pouch for proximal tibial shaft fractures. A technical note. AB - Intramedullary nailing of proximal tibial fractures can be difficult when using the standard entry portal. We evaluated the suprapatellar portal, using a midline quadriceps tendon incision, to perform intramedullary nailing of the tibia. Seven patients were treated with this adaptation of the standard intramedullary nailing procedure. An arthroscopy was done before and after the nailing procedure. No special equipment was used to perform the intramedullary nailing. We evaluated the handling and necessary modifications of the standard intramedullary technique to introduce the locked tibial nail through the suprapatellar approach. We found this technique not necessarily more difficult than the standard intramedullary nailing of the tibia through the infrapatellar entry portal. Although the patients did not complain of patellofemoral discomfort after the suprapatellar nailing, definitive scuffing of the cartilage in the lower part of the femoral trochlea was visible. Introduction of a locked tibial nail via the suprapatellar approach was found to be possible and even advantageous for some complex upper tibial shaft fractures in compromised limbs. Some possible downsides of this approach need to be taken into account but, in some cases, they can be outweighed by the benefits. PMID- 22308633 TI - Closed total talus dislocation: a case report. AB - Total dislocation of the talus is caused by a high-energy trauma, that dislocates the talus from all its surrounding articulations. Most cases reported are open talus dislocations; closed dislocations are rarely seen. Complications include avascular necrosis, posttraumatic osteoarthritis and infection. The vascularisation of the talus is delicate and the soft tissue attachments surrounding the talus are important for the blood supply. Closed talus dislocations, closed reduction and careful surgical dissection in case of open reduction respect more soft tissue attachments and potentially reduce the incidence of avascular of necrosis. We describe the case of a 46-year old male patient who sustained a closed total dislocation of the right talus associated with small fractures of the lateral and medial malleolus. The talus could not be reduced by closed means. The malleolar fractures were treated by open reduction and internal fixation. PMID- 22308634 TI - Metatarsal giant cell tumour in a 7-year-old child: a case report. AB - Giant cell tumours are uncommon benign osseous neoplasias with an obscure origin. They mostly occur in the epiphyses of long bones after skeletal maturity. Occurrence in a metatarsal bone in a child less than 10 years old is quite exceptional. The authors report a case of a 7-year-old girl with an aggressive giant cell tumour of the first metatarsal bone of her right foot. Intralesional excision by curettage and grafting with morselised iliac cortical and cancellous bone was performed. The girl is now disease free since 7 years. Giant cell tumours in this location and age group are rare; they appear to represent a distinct, more aggressive form of tumour. They should be considered in the differential diagnosis of a destructive bony lesion in skeletally immature patients. Curettage and bone grafting with morcelised iliac cortical and cancellous bone remains a treatment option, despite a high potential for recurrence. PMID- 22308635 TI - Spontaneous pediculolysis with associated contralateral laminar fracture. A case report. AB - The authors report the case of a 38 year-old female with a rare combination of spontaneous pediculolysis with an associated contralateral laminar fracture of the lumbar spine. Multimodal radiological examinations of the whole lumbar spine are recommended in the case of a symptomatic patient with low back pain who is not responding to basic physiotherapy and pain management modalities. This will provide the unsuspecting clinician a method to diagnose this rare cause of low back pain and avoid unnecessary surgical intervention. PMID- 22308636 TI - Aneurysmal bone cyst of the spine in an adolescent: a case report. AB - Aneurysmal bone cysts are often localized in long bones of the lower extremity and are characterized by aggressive expansion with local destruction of bone. We present the case of a 14-year-old female patient with a two weeks history of low dorsal pain. Computerized tomography (CT) scan of the spine showed local destruction of the 10th thoracic vertebra and magnetic resonance imaging (MRI) revealed a 50 percent compression of the spinal cord. The partly septated and partly solid cystic tumour in the 10th thoracic vertebra was resected and a dorsal spondylodesis stabilised the thoracic spine. Aneurysmal bone cyst should be considered in the differential diagnosis of unspecific pain of the spine. Follow-up examinations after three, five and twelve months did not show signs of recurrence. PMID- 22308637 TI - The impact of chlordane and dieldrin contamination of well water on cancer rates in North Stamford, Connecticut. AB - BACKGROUND: High levels of the carcinogenic organochlorine pesticides chlordane and dieldrin have been reported in the well water of homes in North Stamford. It is unclear if the contamination is associated with an increase in the cancer rate in North Stamford. METHODS: We reviewed the demographics of the towns surrounding North Stamford and chose New Canaan, Wilton, Weston, and Darien as towns with sufficiently similar demographics that would permit comparison of cancer incidence with North Stamford. Data were obtained from the Connecticut Tumor Registry regarding the number of different cancers diagnosed per year from 1998 to 2007 in North Stamford and the four nearby towns. We compared the annual cancer incidence of these communities in total and by cancer types. RESULTS: There was no statistically significant difference in the average annual cancer incidence from 1998 to 2007 between North Stamford and the four other communities. There was also no statistically significant difference seen in the incidence of the various cancer types. CONCLUSION: Chlordane and dieldrin contamination of the well water of homes in North Stamford may not be associated with a higher incidence of cancer. PMID- 22308638 TI - Progressive massive fibrosis with mixed obstructive and restrictive lung disease and latent period of five decades. PMID- 22308639 TI - Mycobacterium nebraskense as a cause of nodular pulmonary disease. AB - Mycobacterium nebraskense is a scotochromogenic mycobacterium first isolated from sputum samples of five patients at the University of Nebraska Medical Center. M. nebraskense was first identified as a pathogen in an immunocompetent host, also in Nebraska. In this case report, we describe a patient with nodular pulmonary disease most likely due to M. nebraskense, who was successfully treated with rifampin and azithromycin, representing the first case in which this organism was a pathogen outside of Nebraska and the first description of successful treatment of this infection. PMID- 22308640 TI - Early experience with community implementation of thrombolysis three to 4.5 hours after acute ischemic stroke. AB - BACKGROUND: The therapeutic time window for IV thrombolytic treatment was recently extended at Hartford Hospital to 4.5-hours. We assessed the safety and efficacy of delayed thrombolysis. METHODS: All patients given IV tPA for acute ischemic stroke (AIS) since 2006 were assessed. The risk of sICH in patients given tPA < or = three-hours vs > three-hours from onset of symptoms and acute change in NIH Stoke Scale (NIHSS) was evaluated. RESULTS: sICH rates were higher in patients who received IVtPA > three-hours (7.7%, n=39) compared to patients treated in the zero to three-hour window (4.0%, n=251; P = 0.30) but this was not statistically significant. CONCLUSIONS: Administration of tPA in the three to 4.5 hour window appears to be a safe alternative for patients presenting after three hours. Caution is advised however, as sICH rates trended higher in patients in the three to 4.5-hour cohort. PMID- 22308641 TI - Individualized education plans in medical education. AB - BACKGROUND: Individualized education plans (IEP) are commonly used in nonmedical educational programs to define students' deficiencies and action plans for addressing them. There are no reports of using IEP for medical education. SETTING: Internal medicine residency of a community teaching hospital. METHODS: Residents requiring IEP were identified by a consensus of faculty members. IEPs, overseen by mentors, included: 1. List of deficiencies, 2. Techniques for remediation, 3. Schedule for meetings and re-evaluation of IEP progress. Demographic and evaluative data were abstracted from the performance files of internal medicine residents who served in the program between 2003 and 2010. Characteristics and educational outcomes of those receiving IEPs were compared to those not requiring IEPs. RESULTS: Of 92 residents, 16 received IEPs; 13 for medical knowledge, four for professionalism and one for communication.Average age was greater (35.2 vs 30.3 y; P=0.004) and graduation less recent (8.7 vs 4.8 y; P=0.03). USMLE step I and American Board of Internal Medicine in-service scores were lower in those with IEP (82.6 vs 89.4; P=0.001; 44.6 vs 68.5 percentile relative to same-PGY level; P=0.01). Three residents repeated a PGY year (two successfully) and four completed two to six extra months at the same PGY level. All but two residents in the program between 2003 and 2010 passed Boards on their first attempt; neither had an IEP. Of the 12 with successful IEPs, three graduated to primary-care positions, two to hospitalist positions, and six to subspecialty fellowships; one was lost to follow-up. CONCLUSION: A formal IEP process similar to that employed in nonmedical education was associated with successful graduation and board certification in a majority of medical trainees who required remediation. PMID- 22308642 TI - Medical subspecialty hospitalist programs. AB - Hospital medicine is the fastest growing medical specialtyin the United States. Time pressures on primary-care physicians in the office and cost pressures on hospitals are the main driving forces behind this movement. Despite initial criticism and skepticism, hospitalist programs have proven cost effective in clinical and academic departments of internal medicine. These programs have recently been used in medical subspecialty departments as well. Hartford Hospital adopted a new specialty hospitalist program in its cardiovascular department. This program grew to become one of the most successful hospitalist programs in the hospital. Since better quality of care at a lower cost is the ultimate goal for any proposed health-care innovation, we predict that similar subspecialty hospitalist programs will become an accepted part of future hospital care. This article discusses specialty hospitalist care and describes our development of such a program at Hartford Hospital. PMID- 22308643 TI - Surgeons, quality and safety. PMID- 22308644 TI - Message to the 2011 primary-care graduates. PMID- 22308645 TI - Acute psychiatric problems and general hospitals: report of a preliminary survey. 1961. PMID- 22308646 TI - On death and love. PMID- 22308647 TI - Physicians as public servants. PMID- 22308648 TI - Maybe some "lofty journals" shouldn't "last much longer". PMID- 22308649 TI - Re: intracranial hemorrhage from undetected aneurysmal rupture complicating transphenoidal pituitary adenoma resection. PMID- 22308650 TI - No place in medicine for political indifference. PMID- 22308651 TI - Effects of olive oil mill wastewater used as irrigation water on in vitro pollen germination. AB - The aim of this study is to assess the effects of Olive Oil Mill Wastewater (OOMW) application as irrigation water on in vitro pollen germination, focusing on total protein quantity. In test groups, pollen germination substances such as sucrose, H3BO3 and Ca(NO3)2 were added to different concentrations of OOMW and used as germination media. Regarding control group, the same substance melted into water instead of OOMW. As a result, in general, pollen germination percentage was decreased significantly in all OOMW concentrations than that of the control group, except 1/1000 concentrations. Similarly, total protein quantities declined linearly depending on decreasing OOMW concentrations, except 1/1 concentration which has 4-5 times the control value. Consequently, it was established that OOMW generally decreased pollen germination ratio and had carcinogenic effects on protein synthesis mechanism and must not be used as irrigation water without purification. PMID- 22308652 TI - Gastrointestinal parasites of captive and free-roaming primates at the Afi Mountain Primate Conservation Area in Calabar, Nigeria and their zoonotic implications. AB - A study on the gastrointestinal parasites among free-living and captive primates at the Afi Mountain, Primate Conservation Area in Calabar, Nigeria was undertaken for the first time to ascertain their zoonotic implications. Faecal samples were subjected to direct smear, floatation, quantitative estimation of helminth eggs (epg) and oocysts (opg), larval isolation and identification by modified Baerman's technique and oocyst sporulation for specie identification. Out of the 108 primates examined, 75(69.44%) were found to be shedding the ova and oocysts of several gastrointestinal parasites of which, the mona monkeys (Cercopethicus mona) 16(80%) followed by the white collared mangabey (Cercocebus torquatus) 7 (77.78) had the highest (p < 0.05) prevalence of infection. Meanwhile, the chimpanzees (Pan troglodytes) had the highest ova or oocyst counts and variety of gastrointestinal parasites such as Ascaris lumbricoides, Trichuris trichiura, Balantidium coli, Enterobius vermicularis, Entamoeba histolytica, Strongyloides stercoralis, Blastocystis hominis, Hymenolepis nana, Schistosoma mansoni, Ancylostosoma duodenale and Cryptosporidium species. Similarly, the drill (Mandrillus leucophaeus), Sclater's white-nosed monkey (Cercopethicus erythrotis sclateri), white-collared mangabey (Cercocebus torquatus) and others, had Ascaris lumbricoides or Ancylostoma duodenale. All captive primates were more infected than those under free-roam. The young (< 12 months) and females had higher infection rates (p < 0.05) than their counterparts. In conclusion, the primates harboured several parasites of zoonotic importance. PMID- 22308653 TI - Comparing analgesic effects of a topical herbal mixed medicine with salicylate in patients with knee osteoarthritis. AB - Knee osteoarthritis is the most common cause of disability among people and it is a common disease of joints that can lead to cartilage damage. In this study the analgesic effects of a herbal ointment containing cinnamon, ginger, mastic (Saghez) and sesame oil is compared with Salicylate ointment in patients suffering from knee osteoarthritis. It was a double-blind randomized controlled trail study. Patients with diagnosed arthritis were involved in the study and they were divided in two groups via block randomization method. For six weeks, twice a day, intervention group applied herbal ointment and control group used Salicylate ointment. The severity of pain, morning stiffness and limited motion were measured using Visual Analog Pain Scale. In order to analyze the trends of these three indexes, repeated measurement test was used. Ninety two participates with the mean age of 52.2 (+/- 12.4) years and with the mean disease period of 30.45 (+/- 30.3) months were involved in the study. There was no significant difference between two groups regarding the distribution of sex, weight, height, BMI and the duration of illness. No statistical difference was observed between two groups regarding pain relief, morning stiffness and limited motion; nevertheless in repeated measurements during second, forth and sixth weeks in both groups the decreasing trend of these three indexes had been statistically significant (p < 0.0001). It seems that using this herbal combination is clinically effective for patients suffering from knee osteoarthritis in order to decrease their pain, morning stiffness and limited motion; its effect is comparable with Salicylate ointment. PMID- 22308654 TI - Effects of Polygonum aviculare herbal extract on sperm parameters after EMF exposure in mouse. AB - Electromagnetic fields with high energy same as ionizing radiation inserts their destructive effects via free radical production. Using antioxidants or herbal plants with antioxidants components could diminish hazardous effects of EMF. Polygonum aviculare has a high amount of phenolic and flavonoid and proved that has antioxidants effects. The aim of this study was to evaluate the effects of Polygonum aviculare herbal extract on sperm parameters after EMF exposure in mouse. Twenty four male mice, 8 weeks divided to 4 groups (one control and three experimental groups). Control group didn't receive EMF exposure. EMF group mice received 3 mT EMF during 2 months, 4 h daily and 5 days weekly. Polygonum aviculare group received 50 mg kg(-1) herbal extract during 2 months and poly EMF group received 3 mT EMF during 2 months, 4 h daily and 5 days weekly and 50 mg kg(-1) herbal extract during 2 months. After 2 months the mice sacrificed with cervical dislocation and sperm obtained from tail of epididymis and motility and morphology of them were analyzed. Sperm analysis results showed that in group with Polygonum aviculare, morphology and motility of sperm developed (p < 0.05). Present results showed that EMF can reduce motility of sperm and treatment of Polygonum aviculare after EMF exposure developed sperm quality after EMF exposure. PMID- 22308655 TI - The effect of fat supplementation in Shami goat diets on milk production and composition, does body weight and growth performance of their suckling kids. AB - The aim of this study was to evaluate the effect of feeding a dry fat source to Shami does on their milk production and composition, body weight change, weaning weight and average daily gain of their suckling kids. For this purpose we used thirty two multiparous Shami does weighing (47.43 +/- 1.38 kg) and randomly assigned into four dietary treatments in a Completely Randomized Design (CRD) set. Does were housed with their suckling kids and fed one of four isonitrogenous total mixed rations containing 0, 2, 3 or 4% of dry fat. Milk production and milk fat content were higher (p < 0.05) for fat treated does, with no differences between 2% fat level and control group while there was no differences among groups in milk protein content. Final body weight of does was not affected by fat supplementation while body weight changes were higher (p < or = 0.05) for fat treated groups. Weaning weight and average daily gain of suckling kids were increased (p < or = 0.05) for fat treated does, with no differences between 2% fat level and control group. It is concluded that supplemental fat to does rations at 3 or 4% during their postpartum period can improve their milk production and milk fat content, as well as body weight change of does, weaning weight and average daily gain of suckling kids, without any effect on their milk protein content. PMID- 22308656 TI - Study of structure-activity relationship in Aurein 1.2 analogs. AB - Two new analogs of Aurein 1.2 antimicrobial peptide were synthesized and the antimicrobial activities were investigated. The results showed that the activity of G1R/F3W analog was higher than the native peptide and the F3W analog. Circular dichroism studies also showed that the secondary structure of the F3W was concentration-dependent, whereas, there was no such relationship seen in the case of G1R/F3W analog. It has been proposed that G1R/F3W activity was based on a single mechanism (snorkeling), while Aurein 1.2 and F3W utilized the snorkeling mechanism at low concentrations (0-0.01 mM) and the carpet mechanism at higher concentrations (0.01-0.1 mM). This study suggests that one pay attention to the concentration of biomolecules in peptide-based drug design. PMID- 22308657 TI - Distribution and organization of different cells lining the olfactory epithelium of the Indian minor carp, Labeo bata (Hamilton 1822): a light and scanning electron microscopic analysis. AB - The olfactory epithelium of adult Labeo bata (Hamilton) has been studied by light and scanning electron microscopy. The oval shaped olfactory rosette consists of 26 to 28 primary lamellae arranged on both side of the median leaf like raphe. The middle dorsal portion of the lamellae is provided with linguiform processes. This linguiform process is occupied by sensory epithelium and characterized by the presence of two types of receptor cells, ciliated and with microvillous cells. The apical and basal part of the olfactory lamellae are covered with non sensory epithelium. The non-sensory epithelium is made up of stratified epithelial cells and mucous cells. The surface of the non-sensory epithelium is represented by stratified epithelial cells which are provided with unbranched microridges arranged in a concentric whorl. Variations in the cellular organization in the sensory and non-sensory olfactory epithelium have been highlighted in reference to the olfactory sense of the fish concerned. PMID- 22308658 TI - Hepatotherapeutic effect of Aloe vera in alcohol-induced hepatic damage. AB - There is a lack of reliable hepatotherapeutic drugs in modern medicine in the management of alcohol/drug-induced liver damage. Aloe vera extract has been used in folklore medicine for its medicinal values. This study evaluates the hepatotherapeutic activity of aqueous extract of Aloe vera gel in rats. Sprague Dawley rats were divided into three groups; the negative control, positive control and the extract-treated groups. The negative control received only distilled water daily. The positive control received alcohol, while the extract treated group received aqueous extract of Aloe vera and alcohol. Hepatotoxicity was induced in the positive control and extract-treated rats with alcohol. The hepatotherapeutic effect was evaluated by performing an assay of the serum total bilirubin, alkaline phosphatase, aspartate and alanine transaminases and liver histopathology. Alanine transaminase activities were comparable in all groups. Alcohol treatment alone significantly (p < 0.05) increased total serum bilirubin, alkaline phosphatase and aspartate transaminase activities. Alcohol-induced hepatic dysfunction was abrogated by Aloe vera extract. Histopathological examination revealed that alcohol induced hepatic damage. Aloe vera treatment maintained hepatic architecture similar to that seen in the control. This study shows that aqueous extract of Aloe vera gel is hepatotherapeutic and thus lends credence to the use of the plant in folklore medicine in the management of alcohol-induced hepatic dysfunction. PMID- 22308659 TI - Preliminary studies on growth and fresh weight of lettuce (Lactuca sativa) as affected by clay pot irrigation and spacing. AB - An experiment (Completely Randomized Design) was set up to determine the effects of Clay Pot Sub-surface Irrigation (CPSI) and spacing on the growth and fresh weight of lettuce (Lactuca sativa). The treatments were: CPSI with spacing; 15 x 15 cm, 20 x 20 cm and 30 x 30 cm. Control treatments were Watering Can Irrigation (WCI) with the same spacing as above. Treatments were replicated three times given a total of 18 experimental units. Eighteen large enamel basins of 50/20 cm (diameter/height) were filled with good topsoil and a clay pot buried neck deep in each of the basins. Seedlings were planted in all the eighteen basins. Five Hundred mL of wastewater was applied daily to plants in each container having either clay pot or watering can treatment. Plant height increased from 2.50 to 4.25 cm within 6 Weeks after Transplanting (WAT) under CPSI and only increased from 2.14 to 2.99 cm under WCI. The CPSI also supported better leave growth and fresh weight. The fresh weight of lettuce increased almost two fold under 15 x 15 cm spacing compared to 20 x 20 and 30 x 30 cm. PMID- 22308660 TI - Effect of soybean (Glycine max L.) on the hormonal milieu of male rats. AB - Effect of soybean (Glycine max) on serum level of some sex hormones: testosterone, follicle stimulating hormone (FSH), luteinizing hormone/interstitial cell stimulating hormone (LH/ICSH), estradiol and prolactin in male rats was investigated. Twenty male albino rats of 12 weeks old with similar body weights were assigned to four groups of 5 rats each and treatment with soybean meal at 100, 200 and 300 mg kg(-1) body weight, respectively daily for 8 weeks. Blood samples collected through cardiac puncture were assayed for levels of hormones. There were dose-dependent effects of the soybean meal on the serum concentration of the hormones. The treatment significantly reduced the levels of testosterone and FSH in the serum while it significantly increased the levels of estradiol, LH/ICSH and prolactin. The results show that soybean (Glycine max) had strong capability to disrupt hormonal functions. Hence, its indiscriminate use could increase the risk of infertility in males. PMID- 22308661 TI - The art of not knowing. PMID- 22308662 TI - Identification and assessment of children with developmental disabilities in child welfare. AB - The purpose of this study was to examine the ability of a Child Protective Services (CPS) screening and investigation process to identify children with developmental disabilities. The study used an emergent design, ethnographic interviews, purposive sampling, inductive data analysis, and grounded theory building. Ethnographic interviews were conducted with foster families, administrators, intake screeners, special investigators, and workers in one local CPS office. Participants expressed concern about the prevalence of children with developmental disabilities, lack of understanding of developmental disabilities, their ability to identify disabilities, and training to improve CPS workers' ability to identify children with developmental disabilities. Findings suggest a need to improve screening, determine strategies to improve interview reliability, develop the capacity to conduct developmental assessments, and improve the referral process for unfounded allegations. PMID- 22308663 TI - Spiritual needs in health care settings: a qualitative meta-synthesis of clients' perspectives. AB - Spiritual needs often emerge in the context of receiving health or behavioral health services. Yet, despite the prevalence and salience of spiritual needs in service provision, clients often report their spiritual needs are inadequately addressed. In light of research suggesting that most social workers have received minimal training in identifying spiritual needs, this study uses a qualitative meta-synthesis (N=11 studies) to identify and describe clients'perceptions of their spiritual needs in health care settings. The results revealed six interrelated themes: (1) meaning, purpose, and hope; (2) relationship with God; (3) spiritual practices; (4) religious obligations; (5) interpersonal connection; and (6) professional staff interactions. The implications of the findings are discussed as they intersect social work practice and education. PMID- 22308664 TI - Mental health stigma about serious mental illness among MSW students: social contact and attitude. AB - In this study, the attitudes toward and beliefs about serious mental illness (SMI) held by a group of graduate social work students in the northwestern United States were examined. Mental health stigma was examined with relation to the following factors:participants'level of social contact with SMI populations, adherence to stereotypes about SMI populations, belief in the ability to recover from SMI, and the belief that SMI defines an individual's identity. Measures used to identify mental health stigma included the desire for social distance and restrictions with relation to the SMI population. Survey results from 71 graduate social work students found that a significant number of participants who engaged in friendships with SMI-diagnosed individuals had less desire for social distance from and restrictions toward SMI populations. Participants who indicated that they believed in stereotypes of dangerousness and believed that SMI defines an individual's identity were more likely to express desire for both social distance and restrictions. Implications for social work and further research on the matter are discussed. PMID- 22308665 TI - Current levels of perceived stress among mental health social workers who work with suicidal clients. AB - Mental health social workers are at increased risk of being confronted with fatal and nonfatal client suicidal behavior (CSB). Research has documented personal and professional reactions to CSB; however, empirical evidence describing the potential long-term effects is scarce. This study examined current reactions of perceived stress and continual thoughts of the CSB in 285 social workers. Results from multiple regression suggested that higher levels of secondary traumatic stress immediately following CSB predicted higher levels of current perceived stress, and the more time that had passed since the CSB predicted lower levels of perceived stress. Predictors of current level of thinking about the CSB included time since the CSB and whether the social worker completed the grieving process. Implications for social work practitioners, supervisors, and educators are discussed. PMID- 22308666 TI - Design-based practice: a new perspective for social work. AB - Evidence-based practice (EBP) has emerged as an alternative to traditional social work practice and has ignited a new round in the decades-old debate about the relationship between knowledge and practice in the field. This article identifies several limitations inherent in the EBP perspective and argues that it would be unfortunate if EBP were to become the new paradigm for social work practice and education. It also presents a new perspective for social work called design-based practice (DBP), which is based on the work of Herbert Simon and Mary Parker Follett, and compares this perspective with EBP and authority-based practice. DBP rests on the belief that knowledge is derived from experience and interactions between practitioners and clients and that professional practice should be primarily concerned with "how things ought to be." PMID- 22308667 TI - Eugenics, genetics, and the minority group model of disabilities: implications for social work advocacy. AB - In the United States, genetic research, as well as policy and practice innovations based on this research, has expanded greatly over the past few decades. This expansion is indicated, for example, by the mapping of the human genome, an expansion of genetic counseling, and other biogenetic research. Also, a disability rights movement that in many ways parallels other "minority" rights campaigns has expanded. The coexistence of these developments poses intriguing challenges for social work that the profession has yet to address in a meaningful way. These issues are especially pertinent for social work professionals in the crucial role as advocates for marginalized populations. This article describes some ofthe concerns of disability rights activists relative to genetic innovations and goals as well as the instrumental role of the social work community in this important debate. PMID- 22308668 TI - Social work and juvenile probation: historical tensions and contemporary convergences. AB - Social work's weak presence in the field of corrections is peculiar, given that those involved in the criminal andjuvenile justice systems are undeniably among the vulnerable and oppressed populations that the profession has traditionally served. The field of juvenile probation shares roots with the profession of social work but lacks a strong connection to it today. Traditional explanations focus on the reluctance of social workers to engage clients in coercive environments, but historical analysis suggests that this account tells only part of the story. An examination of social work's origins shows that issues involving gender stereotyping and the failure of theory help explain social workers' diminished role in juvenile probation. In recent decades, changes in attitudes regarding gender and working with coerced clients, as well as evidence of effective interventions, suggest that social workers may be ready to reengage meaningfully with juvenile probation and other corrections work. This article outlines steps in professional education and workforce development that would move the profession toward reintegrating social work into the corrections field. PMID- 22308669 TI - The United Nations Convention on the Rights of the Child: children can wait no longer for their rights. PMID- 22308670 TI - What happened to self-determination? PMID- 22308671 TI - [Prediction of multi-target of Aconiti Lateralis Radix Praeparata and its network pharmacology]. AB - OBJECTIVE: To predict multi-targets by multi-compounds found in Aconiti Lateralis Radix Praeparata and construct the corresponding multi-compound-multi-target network. METHOD: Based on drug-target relationships of FDA approved drugs, a model for predicting targets was established by random forest algorithm. This model was then applied to predict the targets of Aconiti Lateralis Radix Praeparata and construct the multi-compound-multi-target network. RESULT: The predicted targets of 22 compounds of Aconiti Lateralis Radix Praeparata are validated by literature. Each compound in the established network was correlated with 16. 3 targets on average, while each target was correlated with 4. 77 compounds on average, which reflects the "multi-compound and multi-target" characteristic of Chinese medicine. CONCLUSION: The proposed approach can be used to find potential targets of Chinese medicine. PMID- 22308672 TI - [Network pharmacology study on major active compounds of Fufang Danshen formula]. AB - OBJECTIVE: To investigate the correlations between multi-compounds of Fufang Danshen formula and their multi targets and multi diseases. METHOD: Literature knowledge of nine major active compounds from Fufang Danshen formula, including tanshinone II(A), salvianolic acid B, protocatechuic aldehyde, danshensu, cryptotanshinone, notoginsenoside R1, ginsenoside Rg1, ginsenoside Rb1 and borneol were collected from PubMed. Combined with cardiovascular related diseases and genes from OMIM database, the corresponding multi-compound-multi- target multi-disease network was constructed and visualized by Cytoscape software. RESULT: AND CONCLUSION: Network analysis showed that the 9 compounds could modulate 42 cardiovascular associated genes (e. g. PPARG, ACE, KCNJ11, KCNQ1, ABCC8, et al), which related to 30 cardiovascular associated diseases including non-insulin-dependent diabetes mellitus, hyperinsulinemic hypoglycemia, hypertension, and coronary heart disease. These results suggested new potential indications of Fufang Danshen formula. PMID- 22308673 TI - [Symptom-based traditional Chinese medicine slices relationship network and its network pharmacology study]. AB - OBJECTIVE: To discover and interpret the correlations between traditional Chinese medicine (TCM) slices and their properties such as function, symptom and channel tropism by constructing the relationship network using network pharmacology approaches. METHOD: TCM slices related information was extracted from Chinese Pharmacopeia (2010 edition, volume I) by text mining, and was used to construct the TCM slices-symptom relationship network. The corresponding network analysis was also performed. RESULT: Three thousands and sixteen pair of TCM slice-symptom correlation associated with 646 TCM slices was discovered, and the constructed network unfolded the complex relationships between TCM slices. Further network analysis results indicated that the un-annotated function and channel tropism of TCM slice can be revealed by proposed symptom-based network. CONCLUSION: Network pharmacology approaches can be applied in TCM research to discover and interpret the relationships between TCM slices and their properties. PMID- 22308674 TI - [Network toxicology and its application to traditional Chinese medicine]. AB - The concept and framework of network toxicology and network toxicology of traditional Chinese medicine has been proposed in this paper. The related tools and technologies have been briefly introduced, and the prospects for network toxicology of traditional Chinese medicine are forecasted. PMID- 22308675 TI - [Tools for network pharmacology study: network visualization and network analysis]. AB - Network pharmacology has been one of the academic frontiers of traditional Chinese medicine research. In this paper, we generally showed the work flow of network pharmacology research, and introduced concepts of network visualization and network analysis, as well the commonly-used tools, such as Cytoscape. PMID- 22308676 TI - [Isolation and analysis of polymorphic microsatellite loci in Dendrobium huoshanense]. AB - OBJECTIVE: To investigate the genetic diversity and structure of Dendrobium huoshanense, a (CT)n enriched microsatellite library was constructed using a magnetic beads enrichment procedure. METHOD: The 3'-biotinylated oligonucleotide probe was used to hybridize with the digested D. huoshanense genomic DNA fragments whose both ends were ligated with adaptors. The hybridized complex was then combined with the streptavidin-coated magnetic beads. The captured microsatellite fragments were eluted, collected and cloned into pMD19-T vector. The recombinant plasmids were transformed into Escherichia coli DH5alpha competent cells. The clones that yielded two or more bands contained microsatellite fractions. Positive clones were screened and sequenced. Thirty pairs of primers were designed and synthesized. Polymorphism at each locus was determined using 24 individuals from a natural population from Huoshan county town in Anhui province. RESULT: Twelve polymorphic microsatellite loci from the microsatellite-enriched genomic library were newly developed across 24 D. huoshanense individuals. In total, 65 alleles were identified, and the number of alleles per locus ranged from 2 to 8. The mean observed and expected heterozygosities were 0.500 and 0.638, respectively. Two loci significantly deviated from Hardy-Weinberg equilibrium (P<0.05), which could be due to the presence of null alleles. Furthermore, three of twelve loci showed significant linkage disequilibrium (P<0.05). CONCLUSION: These results suggest that the identified polymorphic microsatellite markers will be useful in population genetic studies of D. huoshanense. PMID- 22308677 TI - [Effect of optimized fertilization on spicas biomass and yield of Prunella vulgaris]. AB - OBJECTIVE: To study the effects of nitrogen (N), phosphorus (P2O5), potassium (K2O) and organic compound fertilizer (OF) on spicas biomass and yield of Prunella vulgaris in order to provide a theoretical basis for good agriculture practice (GAP). METHOD: Field plot experiments with a 4-variable quadratic orthogonal rotation combination design were adopted, and a function model of spicas yield in P. vulgaris was established. RESULT: The model analysis showed that spicas yields of P. vulgaris were significantly influenced under the N, P2O5 and K2O applications, among there factors, N had the greatest effects on spicas yield of P. vulgaris, the next was P2O5 and K2O, OF had the smallest effects on spicas yield. At the lower fertility levels, the spicas yields of P. vulgaris were improved along with the increasing of N, P2O5, K2O and OF applications, but the spicas yields decreased when N, P2O5, K2O and OF were applied too much. CONCLUSION: In this experiment condition, the spicas yields of P. vulgaris could reach to 722 kg x hm(-2) when the fertilizer rates were N 303. 9-335.1 kg x hm( 2), P2O5 432.5-500.6 kg x hm(-2), K2O 206.6-240.2 kg x hm(-2), OF 2 312.5-2 687.5 kg x hm(-2). PMID- 22308678 TI - [Effects of controlled atmosphere storage on fruit quality of Siraitia grosvenorii during storage]. AB - To explore the condition of CA storage for fruit of Siraitia grosvenorii. METHOD: The CA storage of 5% CO2, 15% CO2, 30% O2 under normal temperature was applied in the experiments, and the results were compared. RESULT: The results showed that CA storage condition could alleviate the reduction of weight loss and water content, the best CA storage condition were 5% CO2, which alleviates the reduction of firmness and increases of soluble solid content during the 45 day period. PMID- 22308679 TI - [Effects of light intensities endogenous hormones of Bletilla striata during acclimatization]. AB - OBJECTIVE: The effect of light intensities on the endogenous hormones of Bletilla striata during seedling acclimatization was studied in order to explain the mechanism and provide basic data for conservation and cultivation of this wild medicinal species. METHOD: The samples was treated with three photosynthetic photon flux densities: 3 000, 6 000, 12 000 lx during the acclimatization stage to study the hormone dynamic changes of IAA, ABA, GA3. RESULT: Endogenous IAA concentration was declined in all treatments and the lowest level in all treatments was the middle light intensity. A sharp increase of endogenous ABA concentration in a short period, the concentration was increased by 380.2% in middle light (320.8 ng x g(-1)). Endogenous GA3 concentration was declined especially in the high light treatment. At 10 days of acclimatization the GA3 concentration was decreased by 52.2% in the high light (473.6 ng x g(-1)). RESULT: Endogenous hormones concentration could be rapidly changed by the light, and endogenous ABA concentration could be sharply increased when acclimatization in middle light intensities. PMID- 22308680 TI - [Effects of harvesting stage on functional constituents of four kinds of Hangbaiju]. AB - To reveal the effects of harvesting stage on the functional constituents of four kinds of Hangbaiju and determine the best harvesting stage. Sixteen samples of Hualei, Taiju, Youju, Quanju were collected from Zhejiang Tongxiang. The content of total flavonoids were determined by UV spectrophotometry. Chlorogenic acid, lutelin-7-O-beta-D-glucoside and 3,5-O-discaffeoylquinc acid were analyzed by HPLC. The results showed that the effect of harvesting stage on the functional constituents of four kinds of Hangbaiju was significant. The contents of total flavonoids and chlorogenic acid reached maximum at the Hualei stage, and next was Taiju. The highest content of lutelin-7-O-beta-D-glucoside and 3,5-O discaffeoylquinc acid was found in samples of Taiju. The yield of the four kinds of Hangbaiju increased obviously as the collection time deferred. Considering the functional constituents, yield and harvesting stage, the stage of Taiju is the best harvesting time. PMID- 22308681 TI - [Study on balance group in steady-state extraction process of Chinese medicine and experimental verification to Houttuynia cordata]. AB - OBJECTIVE: To establish and experimental verification the mathematical model of the balance groups that is the steady-state of traditional Chinese medicine in extraction. METHOD: Using the entropy and genetic principles of statistics, and taking the coefficient of variation of GC fingerprint which is the naphtha of the Houttuynia cordata between strains in the same GAP place as a pivot to establish and verify the mathematical model was established of the balance groups that is the steady-state of traditional Chinese medicine in extraction. RESULT: A mathematical model that is suitable for the balance groups of the steady-state of traditional Chinese medicine and preparation in extraction, and the balance groups which is 29 683 strains (approximately 118.7 kg) were gained with the same origin of H. cordata as the model drug. CONCLUSION: Under the GAP of quality control model, controlling the stability of the quality through further using the Hardy-Weinberg balance groups of the H. cordata between strains, the new theory and experiment foundation is established for the steady-state of traditional Chinese medicine in extraction and quality control. PMID- 22308682 TI - [Preparation of paeonol-beta-cyclodextrin inclusion complex loaded colon specific delivery tablets]. AB - OBJECTIVE: To prepare paeonol-beta-cyclodextrin inclusion complex (Pae-beta-CYD) loaded colon-specific release tablets. METHOD: The core tablets were prepared with the mixture of Pae-beta-CYD inclusion complex, peotin and calcium acetate, and coated with ethanolic solution of Eudragit S100. The effects of coating weight, amount of plasticizer, curing time and temperature on the release of drug from tablets were investigated in vitro. RESULT: About 5-6 h retarded release of paeonol in the dissolution media of pectinase or rats colon contents were obtained by 12% coating weight gain and 20% Dibutyl phthalate (DBP) was used as plasticizer, and subsequently curing the tablets at 45 degrees C for 12 h. CONCLUSION: Pae-beta-CYD loaded colon-specific release tablets showed pH environment and enzyme dependant release properties. PMID- 22308683 TI - [Percutaneous permeability study for patches Shangshi Zhitong on different kinds of bases]. AB - OBJECTIVE: To study the percutaneous permeability of patches Shangshi Zhitong on different kinds of bases with the permeation percentage of brucine, strychnine and atropine. METHOD: Using modified Franz difusion to investigate the penetration quantity of brucine, strychnine and atropine. The contents of brucine, strychnine and atropine were determined by HPLC. RESULT: The average accumulative permeation percentage of brucine, strychnine and atropine on new base were 53.25%, 74.52% were 34.32%, respectively, and on old base are 54.90%, 50.24%, 46. 54%, respectively. CONCLUSION: The new base benefits the lipophilic drugs and releases more stably. PMID- 22308684 TI - [In-line monitoring of blending process of Zhongsheng pill powder using miniature near-infrared analyzer]. AB - OBJECTIVE: To establish a simple and rapid method based on diffuse reflectance NIR spectra to in-line monitor the blending process of Zhongsheng pill powder. METHOD: Zhongsheng pill powder consisted of Zhongsheng spray powder, artificial cowbezoar powder and bile arisaema powder. By means of a revolutionary miniature near-infrared analyzer mounted onto the blender, the powder homogeneity was determined in real time with noninterference. The moving block standard deviation (MBSD) method was used to identify the end point of blending process, providing real-time data and instant feedback about the blending course. Evaluation of blend uniformity was carried out by stratified in-process sampling, and the content of baicalin in samples was determined by high performance liquid chromatography (HPLC). RESULT: The results calculated through MBSD method were generally coincided with HPLC analysis. Blend homogeneity was assumed to be reached when the standard deviations between spectra approached 0.002, and RSD values of baicalin content in samples from six positions were lower than 5%. Moreover, stratified in-process sampling has significant influence on blending process when the powder loading volume was small. CONCLUSION: Based on this study, NIR spectroscopy can be possibly extended to be applied in blending process of Zhongsheng pill powder, ensuring a remarkable saving of time and manpower employed and creating a reliable and efficient process measurement technology. PMID- 22308685 TI - [Study on relationship of properties and drug release rate of hot melt pressure sensitive adhesive]. AB - OBJECTIVE: To investigate the relationship of properties and drug release rate of hot melt pressure sensitive adhesive (HMPSA), and to provide a recommendation of preparing and selecting of HMPSA for transdermal use. METHOD: HMPSA with different properties were prepared using styrene-isoprene-styrene triblock copolymer as main material, and the tacks, adhesions and cohesions were determined. Drug-in-adhesive type patches were prepared using alpha-asarone as model drug, and the drug release rates were investigated on single chamber diffusion cells using 60% ethanol solution as release media. RESULT: The prepared HMPSAs had different tacks, adhesions and cohesions. The drug release rates of HMPSA patches were related to the cohesions. The release rate decreased when the cohesion increased. CONCLUSION: The HMPSA with appropriate cohesion should be selected when preparing patches to balance the drug release rate and patch property. PMID- 22308686 TI - [Study on technology in preparation of Fructus Auranti extract]. AB - OBJECTIVE: To optimize the method of Fructus Auranti extracts preparation. METHOD: The extraction conditions and resin type were examined by using naringin as main indices. The sampling amount, the elution solvent and their flow rates were optimized. The recycling times and recovery capacity of resin were also studied. RESULT: The best extraction could be obtained by adding 10 times amount of NaOH (pH 11) for 3 times, 1 hour each time. The purification conditions were specified as follows: using D101 macroporous resin, the sampling ratio of resin weight to raw material was 1:0.8 with a flow rate of 2 BV x h(-1) and 4 BV 50% aqueous ethanol as elusion solven. CONCLUSION: By using this method, the naringin in the product could reach above 30%. Besides, the optimum method is simple and practical. PMID- 22308687 TI - [Flavonoids from Artocarpus hypargyreus]. AB - OBJECTIVE: To investigate flavonoids from Artocarpus hypargyreus. METHOD: The compounds were isolated by various chromatographic methods and identified by spectroscopic analysis. RESULT: Ten compounds were isolated and their structures were identified as artohypaflavone (1), brosimone H (2), artonin A (3), artocarpin (4), artopetelin B (5), (-)-epiafzelechin (6), oxyresveratrol (7), (+) afzelechin (8), (+)-catechin (9), and (+)-afzelechin-3-O-alpha-L-rhamnopyranoside (10). CONCLUSION: Compound 1 is a new isoprenylated flavone, while compounds 2, 4 6, and 8 were isolated from this plant for the first time. PMID- 22308688 TI - [Anthraquinones from the roots of Knoxia valerianoides]. AB - OBJECTIVE: To investigate the chemical constituents of the roots of Knoxia valerianoides and their biological activities. METHOD: The anthraquinones were isolated by using a combination of various chromatographic techniques including column chromatography over silica gel, Sephadex LH-20, and reversed-phase HPLC. Structures of the isolates were identified by their physical-chemical properties and spectroscopic analysis including 2D NMR and MS. Antioxidant, anti-HIV, neuroprotective, and cytotoxic activities were screened by using cell-based models. RESULT: Twenty-two constituents were isolated from an ethanolic extract of the roots of K. valerianoides. Their structures were identified as nordamnacanthal (1), ibericin (2), rubiadin (3), damnacanthol (4), 2 ethoxymethylknoxiavaledin (5), 3-hydroxymorindone (6), knoxiadin (7), 2-formyl knoxiavaledin (8), lucidin (9), xanthopurpurin (10), 1, 3-dihydroxy-2-methoxy-9, 10- anthraquinone (11), lucidin(-methyl ether (12), digiferruginol (13), 3 hydroxy-2-methyl-9,10-anthraquinone (14), rubiadin-1-methyl ether (15), 6 methoxylucidin (-ethyl ether (16), 1,3,6-trihydroxy-2-methyl-9,10-anthraquinone (17), 1,3-dihydroxy-2-hydroxy methyl-6-methoxy-9,10-anthraquinone (18), 1,3,6 trihydroxy-2-methoxymethyl-9,10- anthraquinone (19), 3,6-dihydroxy-2- hydroxymethyl-9,10-anthraquinone (20), and 1,6-dihydroxy-2-methyl-9,10-anthra quinone (21). In the in vitro assays, at a concentration of 1 x 10(-5) mol x L( 1), no compounds were active against human cancer cell lines (HCT-8, Bel7402, BGC 823, A549, and A2780), deserum and glutamate induced PC12-syn cell damage, LPS induced NO production in macrophage, Fe2+-cystine induced rat liver microsomal lipid peroxidation, HIV-1 replication, and protein tyrosine phosphatase 1B (PTP1B). CONCLUSION: Compounds 9-21 were obtained from the roots of K. valerianoides for the first time. PMID- 22308689 TI - [Inhibitory effect of total bufadienolides from toad venom against H22 tumor in mice and their metabolites]. AB - OBJECTIVE: To evaluate the inhibitory effect of total bufadienolides from toad venom against H22 tumor in mice and preliminarily analyze the structures of the metabolites in tissues. METHOD: HPLC and LC-MS were used for analysis of the chemical composition of TBFs. High, middle and low dosages of TBFs were orally administered or intra-peritoneally injected to H22 tumor-bearing mice for thirteen days. The animals were killed and the tumors were stripped and weighed. The metabolites in the tissues such as heart, liver, spleen, lung and kidney, were analyzed by HPLC and LC-MS. RESULT: The chemical composition of TBFs were identified by comparison of the retention times with those of reference substances, on-line UV spectra and MS data. Its main components are concerned with gamabufotalin, arenobufagin, bufotalin, resibufagin, cinobufotalin, bufalin, cinobufagin and resibufogenin. TBFs had no obvious influence on body weight of H 22 tumor-bearing mice orally administered and the inhibition rate against tumor were 14.76%, 16.38% and 10.32% for low (5 mg x kg(-1)), middle (10 mg x kg(-1)) and high dosage (20 mg x kg(-1)), respectively. The mice intra-peritoneally injected with middle and high-dose of TBFs gained body weight slower than the control mice on the 5th day and recovered on the 13th day. The inhibition rate against tumor were 17.30%, 19.80% and 40.95% for low (1.5 mg x kg(-1)), middle (3 mg x kg(-1)) and high dose (6 mg x kg(-1)), respectively. The inhibitory effect took on dose-dependent manner. Based on the HPLC analyses on heart, liver, spleen, lung and kidney, bufadienolides were found in the liver tissue and 11 compounds of them were tentatively identified by LC-DAD-MS. CONCLUSION: TBFs by oral administration had no inhibitory effect against H22 tumor in mice, however, TBFs by intra-peritoneal injection displayed the significantly inhibitory effect, accompanying some toxicity for early duration of the study. The identification of bufadienolides in the liver provides a good basis for the further investigation of the metabolic pathways of TBFs in vivo. PMID- 22308690 TI - [Testing and analysis of inorganic elements in 466 traditional Chinese medicines materials]. AB - OBJECTIVE: This study attempts to test the total amount of 41 inorganic elements in traditional Chinese medicine materials (TCMM), to analyze to surpass the set standard of 5 toxic heavy metal elements and to explore possible method of modification. METHOD: By using microwave as digestion tool, ICP-MS and ICP-AES as detective instrument, 41 elements in 466 samples are tested. While the amount of elements Al, Ca, Fe, K, Mg, Mn, P, S, Sr are determined by ICP-AES, the amount of the rest 32 elements are determined by ICP-MS. SPSS 16.0 is used as the statistical tool for data analysis. RESULT: Testing of reference material Astragalus showed that the measurements of each element are within the reference range, and except for element I, RSD of determination for each element is less than 10%, thus the accuracy and precision of the study method is confirmed. Using above mentioned instruments and methods, general information of elements in 466 TCMM are obtained. CONCLUSION: The concentrations of each elements in TCMM varied a lot and are different among each TCMM. The over standard rate of 5 heavy metal elements are lower than previous results, however, the over standard rate is still descending in the order of Cd > Cu > Pb > As > Hg. The content of heavy metal elements in TCMM varies among different areas, especially, over standard of heavy metals are not detected in locality as Gansu, Qinghai, Shanxi, Xinjiang and Hainan provinces. PMID- 22308691 TI - [Research of therapeutical effect and immunologic mechanism of Jiawei Foshou San on model rats of endometriosis]. AB - OBJECTIVE: To explore the effect and mechanism of Jiawei Foshou San on the accretion ectopic endometrium of rats. METHOD: Endometriosis model was established by surgical implant of endometrial tissue which belongs to its body in rats. Jiawei Foshou San was administrated to the model rats. Twenty-eight days later, the length of ectopic endometrium was measured by vernier caliper, the spleen was weighed by electronic balance, the content of tumor necrosis factor (TNF)-alpha in blood serum and peritoneal fluid was detected by ELISA test, the expression of interleukin (IL)-8 in ectopic endometrium was detected by immunohistochemical method, the expression of NF-kappaB p65 protein and inhibitory KBalpha (IkappaBalpha) protein in ectopic endometrium were analyzed by western blot. RESULT: Jiawei Foshou San 0.045, 0.09, 0.18 g x kg(-1) group reduced the volume of ectopic endometrium. Jiawei Foshou San 0.18 g x kg(-1) group raised the spleen exponent of model rats. Jiawei Foshou San 0.09, 0.18 g x kg(-1) group decreased the content of TNF-alpha in blood serum and peritoneal fluid, and the content of IL-8 in ectopic endometrium was also decreased. Jiawei Foshou San can decrease the expression of NF-KB p65 and increase the expression of IkappaBalpha in ectopic endometrium. CONCLUSION: Jiawei Foshou San can inhibit the accretion of endometriosis implants of rats, and its mechanism might be associated with improving the environment of body. PMID- 22308692 TI - [Molecular mechanism of tetramethylpyrazine to induce human promyelocytic HL-60 leukemia cells differentiation]. AB - OBJECTIVE: To study the molecular mechanism of tetramethylpyrazine to induce human promyelocytic HL-60 leukemia cells differentiation. METHOD: The cell proliferation was determined by MTT. The differentiation of the cells was detected by NBT reduction test. Cellular morphology was observed by Wright's staining. Cell cycle distribution and the distribution of CD11b, CD14 were detected by flow cytometry. Then RT-PCR and Western blot assay were employed to detect the expressions of c-myc, p27, CDK2 and cyclinE1 in HL-60 cells after exposure to TMP. RESULT: TMP inhibited the proliferation in a dose and time dependent manner. TMP at the concentration of 200 mg x L(-1) to 300 mg x L(-1) induced unterminal differentiation of HL-60 cell and synergistically blocked the cell cycle progression of HL-60 cells in G0/G1 phase. The expression of c-myc was down-regulated as well as the protein expression of cyclin E and CDK2, while the mRNA and protein expression of P27 were remarkably up-regulated. CONCLUSION: Small doses of TMP induces differentiation of HL-60 cells throughout the cell cyde, as detected by a slower rate of accumulation in G0/G1, possibly by regulating the expression and activity of G1/S phase-related molecules. PMID- 22308693 TI - [Effect and mechanism of Andrographitis Herba on human CD4+ T cell promoters CXCR4 and CCR5]. AB - OBJECTIVE: Utilizing a gene reporter technique to study the effects of Andrographitis Herba on human CXCR4 and CCR5 promoters. METHOD: Inhibition of CXCR4 and CCR5 on T cells of healthy volunteers was analyzed by RT PCR, Western blot and flow cytometry. The human CXCR4 and CCR5 promoters driving a luciferase reporter in vectors pGLA. 17-CXCR4 and pGLA. 17-CCR5 were transfected into H9 stem cells. G418 was used for selecting stable cell lines. Rat sera thus medicated was collected and added to the transfected H9 cells, in which the expression of CXCR4 and CCR5 promoters was detected. RESULT: They showed that the mRNA and protein expression levels of CXCR4 and CCR5 in human CD4+ T cells decreased significantly after taking Andrographitis Herba (P<0.05). Furthermore human CXCR4 and CCR5 promoter activity was downregulated significantly by sera from rats medicated with Andrographitis Herba. CONCLUSION: Andrographitis Herba may have the effect of down-regulating CXCR4 and CCR5 promoters. It provides a feasible experimental platform for screening herbal medicine as the treatment of HIV/AIDS. PMID- 22308694 TI - [Research on relationship between tissue quantitative distribution of 3H Achyranthes bidentata ecdysterone and channel-tropism of herbal drugs in mice]. AB - OBJECTIVE: To study the relationship between tissue quantitative distribution and pharmacokinetics of 3H-achyranthes bidentata ecdysterone and the channel-tropism of herbal drugs in mice. METHOD: 3H-achyranthes bidentata ecdysterone was used as a tracer agent and injected into mice by the caudal vein. In 36 hours, the contents of the tracer agent of samples involving 9 different tracing phases and organ or tissue were determined in order to observe the dynamic quantitative distribution and excretion and pharmacokinetics of 3H-achyranthes bidentata ecdysterone and to understand the channel-tropism of herbal drugs achyranthes bidentata. RESULT: 3H-achyranthes bidentata ecdysterone of same organs in different tracing phases and the contents of 3H-achyranthes bidentata ecdysterone in same tracing phases of different organs were significantly different (P<0.01). 3H-achyranthes bidentata ecdysterone was mainly distributed, in the liver, kidney, adrenal gland, small intestine and lung. The concentration-time profiles of achyranthes bidentata ecdysterone in rats injected into mice by the caudal vein were shown to fit a two-compartment open model with half-lives of (778.65 +/ 12.36) min, the elimination of achyranthes bidentata ecdysterone from plasma was found to be in accord with linear kinetics. CONCLUSION: The above mentioned selective distribution of 3H-achyranthes bidentata ecdysterone basically coincides with the meridian affinity and zang fu selection of the traditional Chinese medicine drug Achyranthes bidentata. This study will provide a scientific basis for the channel-tropism of A. bidentata. PMID- 22308695 TI - [Effect and mechanisms of Shenmai injection on contractions of porcine coronary artery]. AB - OBJECTIVE: To investigate the vasodilative action and the possible mechanisms of Shenmai injection on porcine coronary artery. METHOD: Isometric tensions of the porcine coronary artery ring precontracted with potassium chloride (KCl) were recorded in vitro when the doses of 0.1, 0.5, 1, 5, 10, 50 mL x L(-1) of Shenmai injective were cumulatively added into the organ bath of porcine coronary artery ring. RESULT: Shenmai injection caused same vasorelaxation of porcine coronary artery rings with endothelium intact and denuded precontracted with KCl in a concentration-dependent manner. Pretreatment with TEA and 4-AP prohibited the vasorelaxation by Shenmai injection, but pretreatment with KB-R7943, BaCl2, Gli did not affect the vascular effect of Shenmai injection. CONCLUSION: Shenmai injection could produce vasodilatation on KCl pre-contracted porcine coronary artery rings. It seems that K(Ca) and K(V) channel play an important role in the relaxation of the porcine coronary artery rings pre-contracted with KCl. PMID- 22308696 TI - [Explaining syndromes of decoction for removing blood stasis in chest]. AB - Decoction for removing blood stasis in the chest is Wang Qingren's famous formula for promoting blood circulation, the syndromes of which is composed of Sini powder syndrome, Taohong Siwu decoction syndrome, balloonflower syndrome and achyranthes root syndrome. According to many years' research on formula-syndrome and clinical practice of decoction for removing blood stasis in the chest, the syndromes of decoction for removing blood stasis in the chest is analysised from founder decoction, herb-syndrome, original record and constitutional characteristics in order to provide reference for further study. PMID- 22308697 TI - [Research on therapeutic effect and hemorrheology change of berberine in new diagnosed patients with type 2 diabetes combining nonalcoholic fatty liver disease]. AB - OBJECTIVE: To explore the therapeutic effect and the hemorrheology change of berberine in new diagnosed patients with type 2 diabetes combining nonalcoholic fatty liver disease. METHOD: Sixty patients, in our department from March 2009 to March 2010, with type 2 diabetes and nonalcoholic fatty liver disease were randomly divided into two groups. One group was given berberine, another group was given Xuezhikang, both for 12 weeks. The indicators, include B-ultrasound of liver, triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), aspertate aminotransferase (AST), hemorrheology, were detected before and after treatment. RESULT: After treatment by berberine, B ultrasound of liver were better than before, the effective rate was 70%, vs 73.3% after treatment by Xuezhikang. ALT, AST, TC, TG, LDL-L, hemorrheology (including the whole blood viscosity, whole blood viscosity, high cutting reduction of whole blood viscosity, plasma cutting reductive low viscosity, blood sedimentation, RBC deposited, fibrinogen) were significantly lower than before, however, HDL-L significantly increased (P<0.05). The therapeutic effect of xuezhikang was the same as berberine. The distance between the indicators of the two groups was no different. CONCLUSION: Berberine can obviously improve the conditions of new diagnostic T2DM patients with nonalcoholic liver lesions, effectively reduce hemorrheology indicators, and has good application prospect. PMID- 22308698 TI - [Research progress of antitumor components from original animals of traditional Chinese medicine powder of Notarchus]. AB - Powder of Notarchus is a traditional Chinese medicine originated from the eggs of various sea hares species of family Aplysiidae Lamarck, especially Notarchus. leachii cirrosus, Aplysia kurodai and A. pulmonica. It has been used for clinical treatment of cancer and cancer-like diseases in China since the Ming dynasty. Isolation and identification of numerous cytotoxic ingredients from sea hares organisms were reported. Bioactive components of sea hares in China sea including 23 species from six genera of the Aplysiidae were reviewed in this paper. Approximately 300 molecules were identified in 11 species. More than 85 compounds extracted from 7 species were confirmed to have antitumor activity, which indicated that powder of Notarchus would have potential in developing new antineoplastic agents. PMID- 22308699 TI - [Safety research in Chinese medicines based on application of data mining]. AB - The current status of the application of data mining in Chinese medicine (TCM) safety research are analyzed in this paper, and the future development trend are discussed, which include: to establish ADR (adverse drug reaction) signal detection and automatic warning system based on traditional Chinese medicine (TCM) adverse reaction database, to explore the characteristics and influencing factors of TCM safety problems, to devise appropriate new algorithm, and to develop TCM adverse reaction literature mining. PMID- 22308700 TI - [Discussion on appraisal methods and key technologies of arbuscular mycorrhizal fungi and medicinal plant symbiosis system]. AB - Applications of arbuscular mycorrhizal fungi in research of medicinal plant cultivation are increased in recent years. Medicinal plants habitat is complicated and many inclusions are in root, however crop habitat is simple and few inclusions in root. So appraisal methods and key technologies about the symbiotic system of crop and arbuscular mycorrhizal fungi can't completely suitable for the symbiotic system of medicinal plants and arbuscular mycorrhizal fungi. This article discuss the appraisal methods and key technologies about the symbiotic system of medicinal plant and arbuscular mycorrhizal fungi from the isolation and identification of arbuscular mycorrhiza, and the appraisal of colonization intensity. This article provides guidance for application research of arbuscular mycorrhizal fungi in cultivation of medicinal plants. PMID- 22308701 TI - [Textual research on original plant and dietotherapy history of Prunella vulgaris]. AB - OBJECTIVE: To investigate the original plant and dietotherapy history of Prunella vulgaris by textual researches, and provide a theoretical basis for clinical medication, exploitation and protection of wild resources. METHOD: The ancient literatures in the graphic, geographical distribution and morphological description of P. vulgaris were used in this studied. RESULT: The varieties of P. vulgaris for therapeutic were no confusion. However, there has existed confusion between P. vulgaris and its confusable species (Ajuga ciliate, A. decumbens and Lagopsis supina) with appellations, morphological description and attached drawing of original plant. CONCLUSION: The original plant is originated from two species (P. vulgaris, P. asiatica). P. hispida was used as a certified medicinal material in Yunnan province from Ming Dynasty to modern time. The dietotherapy history of P. vulgaris in China can be traced back to Ming Dynasty or before. PMID- 22308702 TI - [Global trends in malaria control. Progress and topical tasks in malaria control programs]. AB - This communication is the first in the series consisting of two publications describing the present state of malaria control and elimination in the world. The global malaria situation in 2009-2010 demonstrated a considerable situation as compared to the previous years. This improvement is associated with a considerable global increase of investments made by both national governments and world society to the malaria control programs. Spectacular progress has been achieved even in the areas of the most infection-affected African countries situated to the south of the Sahara Desert. It has been estimated that malaria cases in the world declined from 233, 000,000 in 2000 to 225,000,000 in 2009. Malaria mortality decreased from 985,000 in 2000 to 781,000 in 2009. To maintain the results achieved and to further reduce the problem of malaria worldwide, it is necessary to ensure a long-term political and financial support for malaria control programs at the national and international levels. PMID- 22308703 TI - [Plasmodium knowlesi: the widespread and human dangerous type of malaria pathogens from the South-Eastern Asia and the Pacific Ocean islands]. PMID- 22308704 TI - [The value of cytokines in immunity in case of echinococcosis]. PMID- 22308705 TI - [Distribution of HLA specificity frequencies in patients with cystic echinococcosis]. AB - This investigation was undertaken to study the associations of the polymorphic variants of the HLA-DRBI and HLA-DQB1 loci with the development of cystic echinococcosis in children. The material for the investigation was collected from 57 children admitted for surgery to the clinic of the Department of Pediatric Surgery, Orthopedics, and Anesthesiology, Bashkir State Medical University (Ufa). The PROTRANS kit (Germany) was used to isolate DNA samples from peripheral venous blood served as an object of the investigations. HLA specificities were typed by polymerase chain reaction. Molecular genetic studies established the association of DRB1*07, DQB1*0.9, DQB1*02 specificities with the increased risk of cystic echinococcosis in children. The echinococcosis cyst suppuration-complicated course of the disease was found to be more frequently encountered in DQB1*02 and DRB1*03 allele carriers. PMID- 22308706 TI - [The clinical and functional state of the liver in patients with psoriasis in the presence of chronic opisthorchiasis]. AB - OBJECTIVE: to study the clinical and functional state of the liver in patients with psoriasis concurrent with chronic opisthorchiasis (CO). SUBJECTS AND METHODS: Twenty-eight patients with psoriasis concurrent with CO, 15 patients with CO, 15 patients with the enlarged liver, and 15 healthy individuals were examined. Serum biochemical study and ultrasonography of the liver and gallbladder were used. RESULTS AND DISCUSSION: The patients with comorbidity were found to have hepatomegaly with syndromes of cytolysis, cholestasis, and mesenchymal inflammation of more degrees than those from Groups 2 and 3. CONCLUSION: The found clinical and functional liver changes in patients with psoriasis concurrent with CO make it necessary to perform anthelmintic therapy in this category of patients. PMID- 22308707 TI - [Amino acid exchange in paeci lomycosis-complicated echinococcosis]. AB - The authors have detected atypical paecilomycosis-associated myocarditis with impaired amino acid exchange and pain syndrome for the first time. At first, pain occurs in the chest and radiates into the axilla, to the left arm to the finger tips, by paralyzing the arm. In some patients, pain manifests itself in both arms with radiation to the belly, by accompanying by fainting. The skin is wet, cold; the pulse is frequent and of poor volume and difficult-to-count. Heart pain spreads into the armpit and down the arm, by making the fingers numb. Attempts to use current analgesics (movalis, sirdalud, nimesil, morphine) in combination with fungicides (diflucan, mycosist, orungal) have failed to yield positive results. The homeopathic drug Latrodectus mactans, prepared from caracurt venom, in combination with the authors' designed diet and other homeopathic agents have relieved pain syndrome and normalized amino acid exchange, which offered possibilities for successful surgical treatment for echinococcosis with later recovery. PMID- 22308708 TI - [Aedes aegypti and Aedes albopictus mosquitoes are the vehicles of arbovirus infection: biology, ecology, spread, and distinctive signs of species]. PMID- 22308709 TI - [Value of fleas in the natural foci of plague in the caucasus]. AB - The paper characterizes the seasonal phenomena of the life cycle of fleas in relation to the intensity of epizootias in the natural foci of plague in the Caucasus. A situation determined by the vital activity of several species of fleas, the parasites of a major vehicle, is, in terms of pathogen transmission, established in each of 9 natural plague foci. They are combined by the nesting borrow type of parasitism, which provides the wide distribution of plague pathogen among rodents. In each focus, there are the most intensive epizootias in the period of high feeding and reproductive activity of transmitters. PMID- 22308710 TI - [Insecticide resistance in lice collected from homeless people in Moscow]. AB - Permethrin and malathion resistance in body and head lice collected from homeless people in Moscow was investigated in March 2009 to March 2010. Most micropopulations were found to have permethrin-resistant individuals. Their proportion varied from 8.7 to 100%. Cross resistance of body lice to 5 insecticides (the pyrethroids permethrin, d-phenothrin, cypermethrin, deltamethrin, and the organic chlorine compound DDT) was revealed in one case. The lice remained susceptible to organic phosphorus insecticides (fenthion, malathion). The data on permethrin resistance in the lice, obtained by the standard method (immersion of the insects into an insecticide solution), correlated with those yielded by the modified WHO method. PMID- 22308711 TI - [Cases confirming the concept that the human being is a facultative host of Dirofilaria repens]. PMID- 22308712 TI - [The preparation of antihymenolepidiasis activity of MCT-44]. PMID- 22308713 TI - [The spread of the pathogen of human and animal clonorchiasis in North Vietnam]. PMID- 22308714 TI - [Use of Dironet for prophylaxis in Dirofilaria immitis-infested working dogs in the Astrakhan region]. PMID- 22308715 TI - [Diagnosis of parasitic diseases in the Russian Federation: state-of-the-art]. PMID- 22308716 TI - [Results of parasitological passportization of sewage treatment works in the South Federal District]. AB - Developed parasitological passports for sewage treatment works have been issued in the subjects of the Southern Federal District. Its some regions have areas inadequately covered by centralized water drainage. New waste treatment technologies and disinvasion agents have not been virtually introduced. No proper significance is attached to the parasitological studies of epidemiologically significant substrates, such as waste waters and their sludge. The positive results of dehelmintization and disinvasion are stated from the absence of helminth eggs rather than from the comparative results of sewer clearing from the invasion principle and their viability loss. Standard guides corresponding to the profile of objects are inadequately used in day-to-day work. PMID- 22308717 TI - [The value of cytokines in immunity in case of opisthorchiasis]. PMID- 22308718 TI - [Nikolai Ivanovich Latyshev (on the occasion of 125th anniversary of his birth)]. AB - This paper is devoted to the scientific activity of Russia's most eminent parasitologist N. I. Latyshev. The paper gives its stages and the main areas of his studies of parasitic tropic diseases (malaria, tick-borne relapsing fever, pappataci fever, leishmaniasis, etc.) in the areas of Central Asia and Caucasus. N. I. Latyshev's scientific works made a great contribution to the teaching of the natural focal pattern of leishmaniasis and could further substantiate the principles of cutaneous leishmaniasis control in the endemic areas. PMID- 22308719 TI - [Sorption properties of various polysaccharide matrixes to Lactobacillus plantarum 8RA-3 bacteria]. AB - AIM: Study of sorption properties of various spherical polysaccharide matrixes designated as Spherocell to probiotic Lactobacillus plantarum 8RA-3 bacteria. MATERIALS AND METHODS: Industrial strain of L. plantarum 8PA-3 was used. The process of immobilization of lactobacilli on 3 variants of spherical sorbents was studied. The first sorbent - neutral, composed of nonpolar cellulose matrix with ("0") charge, the second--DEAE obtained by modification of cellulose by diethylaminoethyl groups with positive ("+") charge and the third--CM (carboxymethyl) with negative ("-") charge. Cellulose matrixes were designated by us by the term Spherocell. Immobilization of bacterial cells on Spherocell was performed by addition of suspension containing 1.0 x 10(9) CFU/ml. The effect of bacterial immobilization was evaluated by CFU/ ml titration and by electron microscopy. RESULTS: The dependence on matrix charge of adsorption immobilization on sorbent granules of lactobacilli cells was shown. At certain equal parameters (granule size, surface characteristics, charge value) the positively charged matrix sorbed 3-10 times more cells than neutral and 20-25 times more than negatively charged matrix. Each 100-180 microm Spherocell DEAE particle could sorb more than 1000 viable bacterial cells. CONCLUSION: Positively charged polysaccharide matrix Spherocell DEAE obtained by modification of cellulose by diethylaminoethyl groups is promising for creation of immobilized probiotic preparations. PMID- 22308720 TI - [The increase of plasmid DNA copy number is a possible mechanism of the amplification of bacteria anti-lysozyme activity under the effect of chloramphenicol]. AB - AIM: Determination of copy number dynamics of plasmid DNA and anti-lysozyme activityunderthe influence of chloramphenicol in cells of Escherichia coli 252 and 242 strains (ICIS), that have identical biochemical profile and differ by antibiotic resistance, plasmid profile and level of anti-lysozyme activity. MATERIALS AND METHODS: E.coli strains were isolated during screening of antibiotic resistant enteric bacteria of human intestinal biotope. The selected strains were cultivated in medium with 0.17; 0.5; 1 and 1.5 MIC of chloramphenicol by nonspecific amplification ofplasmid DNA in medium with chloramphenicol (technique by T. Maniatis et al.). Plasmid DNA was recovered by alkaline lysis method with subsequent electrophoresis in agarose gel. The quantity ofplasmid DNA was evaluated by comparison of luminescence intensity of marker and experimental DNA sample bands. Anti-lysozyme activity was measured photometrically (O.V.Bukharin et al.). RESULTS: E. coli 252 strain had higher direct correlation of bacteria anti-lysozyme activity and increase of plasmid copy number per cell (r > or = 0.9) during increase of chloramphenicol concentration in sub-bacteriostatic range. Dynamics of these parameters in E. coli 242 control strain were not detected. CONCLUSION: The data obtained give evidence in favor of the action of plasmid localized "gene dose" effect as a mechanism of anti-lysozyme activity increase of bacteria under the influence of chloramphenicol. PMID- 22308721 TI - [Development of Streptococcus pyogenes cells inactivation for turbidimetric determination of bacteriolytic activity of phage-associated enzyme]. AB - AIM: Development a method of treatment of Streptococcus pyogenes bacteria that does not disrupt the integrity of surface structure of cell and provides optimal reproducibility of enzyme preparation activity test results. MATERIALS AND METHODS: Museum cultures of S. pyogenes M29 and S. pyogenes T1 were used, as well as standard strain S.pyogenes T5 (ATCC) and 3 phage-associated lysine PlyC preparations (enzybiotics): 2 isolated from phage C1, third--recombinant enzyme obtained by cloning phage C1 DNA. 3 methods of S. pyogenes cells treatment were used: inactivation by chloroform, antibiotics and heating. RESULTS: Treatment of S. pyogenes cells by rifampicin and gentamicin allows simultaneous turbidimetric determination of enzyme preparations activity and streptococci lysis effectiveness with a good reproducibility of test results. Comparison of kinetic curves of streptococci lysis killed by heating with curves of live culture lysis showed that heat treatment of cells results in a decrease oflysis depth and a reduction of enzyme activity. Pattern and effectiveness of lysis of cells incubated with chloroform approached curve of live streptococci lysis, however this method did not exclude lysis of part of cells and required presence of equipment for work with chemical substances. CONCLUSION. S. pyogenes test culture inactivation method by 2-step treatment of culture with antibiotics that does not disrupt the integrity of surface structure of cells and provides optimal reproducibility of enzyme preparation activity test results was developed. PMID- 22308722 TI - [Toxicity and cytokine-inducing activity of lipopolysaccharide of virulent Yersinia pestis 231 strain]. AB - AIM: Determine correlation between toxicity and cytokine inducing activity of parent and conformation modified forms of lipopolysaccharides (LPS) of virulent Yersinia pestis strain. MATERIALS AND METHODS: LPS was isolated by phenol method from Y. pestis 231 cells grown at 37 degrees C (LPS37). LPS37 was modified by "mice" toxin (MT) Y. pestis. Toxicity was controlled in mice. TNFalpha and IFNgamma cytokine production was determined by enzyme immunoassay. The study was performed in human monocytes U-937 cell line. TLR4 re-stimulation was performed after activation of monocytes by S-LPS and R-LPS of Escherichia coli. RESULTS: LPS37 conformation change of virulent Y. pestis 231 strain during formation of complex with "mice" toxin increases its toxicity for animals by 2 times. LPS37 and LPS37-MT induce TNFalpha and IFNgamma synthesis by human monocytes. LPS37 simultaneously activates MyD88-dependent as well as MyD88-independent signal pathways. Modified LPS37-MT form is a strong activator only of MyD88-dependent pathway and thereafter induces synthesis of predominately one of the cytokines- TNFalpha. Monocyte response to primary and recurrent activation by LPS37 and LPS37-MT corresponds to R- and S-LPS E. coli cytokine response profile. CONCLUSION: A direct correlation between toxicity of LPS37 and LPS37-MT and their TNFalpha-inducing activity was demonstrated in the study. LPS37 and LPS37-MT of Y. pestis 231 differentially activates TLR4 signal pathways of human monocytes. PMID- 22308723 TI - [Characteristics of Mycobacterium tuberculosis strains circulating in Pskov region]. AB - AIM: Characteristics of drug resistance (DR) and population structure of Mycobacterium tuberculosis in Pskov region. MATERIALS AND METHODS: In 90 strains of M. tuberculosis drug resistance was studied by culture method and by using "TB BIOCHIP"; genotyping was determined by spoligotyping method. RESULTS: 55 (61.1%) of 90 M.tuberculosis strains had drug resistance, with 40 (44.4%) being multi resistant. M. tuberculosis population was presented by SIT1 spoligotype strains of genetic families Beijing--44.4%, LAM--21.1%, T--14.4%, Haarlem--11.1% and Ural -5.6%, according to SpolDB4. Among M. tuberculosis strains circulating in Pskov region the most widespread (44.4%) was SIT1 spoligotype (p < 0.0001). DR and multi-resistant DR (MDR) in Beijing strains occurred more frequently than in "non Beijing" strains (p < 0.001 and p = 0.03 respectively) and were determined by rpoB mutations Ser531-->Ley and katG Ser315-->Thr. All the SIT252 spoligotype strains were multi-resistant, and their resistance to rifampicin was determined by rpoB Asp516-->Ser substitution, to isoniazid --katG Ser315-->Thr and inhA_T15 substitutions. CONCLUSION: The data obtained gives evidence on tuberculosis epidemiological unfavorability and wide circulation of MDR M. tuberculosis strains in Pskov region. PMID- 22308724 TI - [Control of poliomyelitis and enterovirus infection in several areas of Russian Federation]. AB - AIM: Control of poliovirus circulation by study of material from patients with acute flaccid paralysis and contact individuals, from children of risk groups; molecular characteristics of isolated polioviruses; monitoring of circulation of polioviruses and nonpoliomyelitis enteroviruses in population and the environment. MATERIALS AND METHODS: Isolation and study of polioviruses and nonpoliomyelitis enteroviruses from various sources was performed in accordance with WHO recommendations. RESULTS: Prolonged persistence and circulation of vaccine related strains of polioviruses in children is demonstrated. Enterovirus serotypes that circulate in the population and the environment more frequently are determined. CONCLUSION. Long term control of poliomyelitis and acute flaccid paralysis in combination with additional control variants in children from risk groups and objects of the environment allowed to obtain valuable data on poliovirus and nonpoliomyelitis enteroviruses circulation for the Program of eradication of poliomyelitis. PMID- 22308725 TI - [Actual problems of creation of informational-analytical system for rapid control of epidemics of infectious diseases]. AB - Structure and modules of computer informational-analytical system "Electronic atlas of Russia" is presented, the object of mapping in this system is epidemiology of socially significant infectious diseases. Systemic information on processes of emergence and spread of socially significant infectious diseases (anthroponoses, zoonoses and sapronoses) in the population of Russian Federation is presented in the atlas. Detailed electronic maps of country territory filled with prognosis-analytical information created by using technological achievements of mathematic and computer modeling of epidemics and outbreaks of viral and bacterial infections are of particular interest. Atlas allows to objectively evaluate the pattern of infection spread, prepare prognoses of epidemic and outbreak developments taking into account the implementation of control measures (vaccination, prophylaxis, diagnostics and therapy) and evaluate their economic effectiveness. PMID- 22308726 TI - [Lactobacillus plantarum and phosprenyl competitively distinguish ovalbumin oligomannoside n-glycan]. AB - AIM: Demonstration of the ability of native products of lactobacteria to bind mannose containing N-glycans as a display of one of the mechanisms of probiotic behavior of these symbiont microorganism in gastrointestinal tract (GIT). MATERIALS AND METHODS: Lactobacillus plantarum 30 grown on selective medium (MRS agar) and their ultrasound lysates were used in the study. Standard technique of delayed type hypersensitivity (DTH) reaction was used with inactivated Listeria monocytogenes culture as a priming agent. RESULTS: DTH reaction in vivo has demonstrated that oligomannoside N-glycan of egg albumin is a general acceptor for adhesins that are present in the native preparations of certain L. plantarum strains, as well as for phosprenyl (PHP) immunomodulator--an inhibitor of cell IL 2 reception. CONCLUSION: The data obtained give evidence that mannose specific adhesins that are conserved in lactobacteria preparations have the same binding sites in egg albumin as PHP and, therefore, IL-2. PMID- 22308727 TI - [Microbial "friend-foe" identification in human intestine microsymbiocenosis]. AB - AIM: Development of methodical approach of evaluation of microbial "friend-foe" identification in human intestine microsymbiocenosis. MATERIALS AND METHODS: 9 bifidobacteria cultures (dominants) and 18 opportunistic microorganism strains (associants) isolated from patients during examination for intestine dysbiosis and identified by conventional methods were used. Evaluation of microbial "friend foe" identification in microsymbiocenosis was performed by author developed technique that is based on determination of growth factors (GF), anti-lysozyme activity (ALA) and formation of biofilms (BFF) of associants co-incubated with exometabolites of dominants. GF, ALA, BFF were studied photometrically (Bukharin O.V., 1999, 2009; O'Toole G.A., 2000). The data were statistically analyzed by Fisher-Student criteria. RESULTS: The detected opposite (increase/reduction) phenomenon of the "dominant-associant" pair allowed realization of the "friend foe" identification in microsymbiocenosis. Associants (E. coli and Enterococcus faecium) were "friend" species, in which bifidobacteria exometabolites did not change growth properties and stimulated ALA (by 17,5--32%) and BFF (by 25 - 39%). Associants (Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Candida albicans) were "foe" microsymbiont species, in which bifidoflora exometabolites decreased GF (by 20,7--68%), ALA (by 22,7--54%) and BFF (by 22,5 - 39%). CONCLUSION: Indigenous microflora during microsymbiocenosis formation can participate in "friend-foe" identification, the basis of which is determined by microsymbiont exometabolites. The data obtained open a perspective of understanding mechanisms of intramicrobial interactions and can be used for both diagnostics and optimal selection of "candidates" during creation of new probiotics and synbiotics. PMID- 22308728 TI - [Genetic diversity of Staphylococcus aureus strains that colonize nose mucous membrane of children living in a large industrial city]. AB - AIM: Study of genetic diversity of Staphylococcus aureus strains that colonize nose mucous membrane of children living in an ecologically unfavorable district of Krasnoyarsk. MATERIALS AND METHODS: 20 S.aureus strains isolated from mucous membrane of anterior part of nose of children were genotyped by RAPD-PCR (random ampliphied polymorphic DNA) with an oligonucleotide primer (10 Sh1 nucleotide). RESULTS: Presence of 6 genotypes, with 3 of those including 3 and more strains, was detected among the studied strains. The extent of genetic similarity between genotype 1 and 2 was established at 85%. CONCLUSION: 20 of 63 (31.7%) of examined students were resident carriers of S. aureus. 3 main genotypes of S. aureus that circulate in students were detected by RAPD-PCR. This confirms the necessity to use RAPD-PCR method for timely evaluation of epidemic situation in organized groups of children. PMID- 22308729 TI - [State of immunity to diphtheria and tetanus in women in early postpartum period]. AB - AIM: Study of anti-diphtheria and anti-tetanus immunity in women in early postpartum period depending on age. MATERIALS AND METHODS: Women in early postpartum period (n =139) with unknown vaccine anamnesis aged 17 to 44 years and under the supervision of Rostov-on-Don maternity hospital No. 2 were examined for the evaluation of the anti-diphtheria and anti-tetanus immunity state. RESULTS: All the women had high level of protection form these infections. The level of anti-tetanus immunity intensity in the examined was higher than anti-diphtheria. CONCLUSION: Monitoring of anti-diphtheria and anti-tetanus immunity in women of childbearing age is necessary to resolve the issue of vaccine administration in this group. High level of maternal immunity intensity will allow to form a sufficient protection from infectious agents in neonates. PMID- 22308730 TI - [Dependence of IgG titers specific to various hepatitis C virus proteins on features of chronic infection course]. AB - AIM: Analysis of IgG titers that are specific to various hepatitis C proteins depending on features of chronic infection course. MATERIALS AND METHODS: Qualitative analysis of levels of IgG specific to a number of hepatitis C virus proteins was performed in 30 patients and 30 virus carriers. RESULTS: Significant differences between these HCV infection course variants by level of accumulation of all studied HCV antibody groups were detected. Low a-core and a-NS4 IgG, high a-NS3 and medium a-NS5 titers may be an indicator of HCV carriage. Medium and high a-core, medium a-NS3 and a-NS4 as well as higher a-NS5 titers indicate chronic hepatitis C. CONCLUSION: The proposed method can be used for screening of chronic HCV infection course in the clinical practice. PMID- 22308731 TI - [Influence of electromagnetic emission at the frequencies of molecular absorption and emission spectra of oxygen and nitrogen oxide on the adhesion and formation of Pseudomonas aeruginosa biofilm]. AB - AIM: Evaluate the influence of electromagnetic emission (EME) at the frequencies of molecular absorption and emission spectra of atmospheric oxygen and nitrogen oxide (MAES 02 and MAES NO respectively) on the adhesion, population progress and biofilm formation of Pseudomonas aeruginosa. MATERIALS AND METHODS: Adhesive activity was evaluated by mean adhesion index (MAI) of bacteria on human erythrocytes. Population growth dynamic was assessed by optical density index of broth cultures; biofilm formation--by values of optical density of the cells attached to the surface of polystyrol wells. RESULTS: P.aeruginosa bacteria had high adhesive properties that have increased under the influence of MAES 02 frequency emission and have not changed under the influence of MAES NO frequency. Exposure of bacteria to MAES NO frequency did not influence the population progress; exposure to MAES 02 frequency stimulated the biofilm formation ability of the bacteria, and MAES NO--decreased this ability. CONCLUSION: EME at MAES NO frequency can be used to suppress bacterial biofilm formation by pseudomonas. PMID- 22308732 TI - [Effect of phenol on Yersinia pseudotuberculosis bacteria cultivated in various media]. AB - AIM: Study of bactericidal effect of phenol on Yersinia pseudotuberculosis produced in various nutrient media. MATERIALS AND METHODS: Bacteria were produced in nutrient broth (NB) and NB with glucose (NB+Glu) or galactose (NB+Gal) at 8 degrees C. Effect of phenol on bacteria was evaluated by changes in optical density of suspension and quantity of viable cells, and by staining of cells with ethidium bromide. Lipids were analyzed by thin-layer and gas-liquid chromatography, gas-liquid- chromatography--mass-spectrometry, differential scanning calorimetry; lipopolysaccharides (LPS)--by electrophoresis in polyacrylamide gel in the presence of sodium dodecylsulfate (SDS-PAGE). RESULTS: Survival rate of bacteria is dependent on phenol concentration, biocide treatment time and parameters of cell cultivation. Addition of glucose or galactose into the nutrient medium increases the resistance of Yersinia against phenol. Bacterial cultures are heterogeneous in the resistance against phenol independently of the production parameters. Phenol causes damage in outer bacterial membrane, as evidenced by accumulation of lysophosphatidylethanolamine in the cell, the main product of enzyme activity of membrane-bound phospholipase A, and release into the cultural medium of part of LPS. Treatment by phenol in bactericidal concentration is accompanied by changes in phospholipidic and fatty acid composition of bacterial cell envelope. CONCLUSION: New data are obtained on environmental factors that contribute to the increase of resistance of bacteria against phenolic biocides. PMID- 22308733 TI - [Development and use of test-systems for molecular-genetic detection of out-of hospital pneumonia agents]. AB - AIM: Search of new targets and improvements of molecular-genetic detection methods of species specific DNA fragments of out-of-hospital pneumonia (OP) infection agents in sputum. MATERIALS AND METHODS: Species specific oligonucleotide primers to Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Branhamella catarrhalis were selected. 103 sputum samples from OP patients and 15 from practically healthy humans were test by using PCR and bacteriological method. RESULTS: Mixed bacterial flora was detected by bacteriologic method in OP in 26 cases (25.2%). 14 patients (13.6%) had B. catarrhalis DNA in sputum, 12 patients (11.6%)--S. pneumoniae, H. influenzae was detected in 11 examined individuals (10.7%), K. pneumoniae (7.9%)-- in 8. In 32 cases (30%) etiology of OP could not be deciphered bacteriologically. B. catarrhalis was detected in 19 (18.5%) of OP patients, S. pneumoniae--in 17 (16.5%), H. influenzae and K. pneumoniae--in 14.5% and 12.6% (15 and 13 patients) respectively by Using the developed PCR primers. In 16.5% cases (17 patients) positive results against several bacteria species simultaneously were obtained by PCR method, in 3.9% (4 patients) P. aeruginosa was detected. CONCLUSION. Use of PCR for detection of out-of-hospital pneumonia agents DNA significantly increases informativity of the study when compared with bacteriological method. PMID- 22308734 TI - [Formation of antibodies against neuraminidase of A/California/07/2009 (H1N1) influenza virus after immunization with live monovalent influenza vaccine]. AB - AIM: Detection of antibodies against neuraminidase (NA) of A/California/07/2009 (H1N1) influenza virus in blood sera of volunteers after the immunization with live monovalent influenza vaccine (LIV). MATERIALS AND METHODS: Neuraminidase enzyme activity inhibition by antibodies test with reassortant strain A(H7N1) containing NA of pandemic strain was used. Anti-neuraminidase IgG antibodies against whole reassortant virus A(H7N1) and purified NA of A/California/07/2009 (H1N1) strains were determined by enzyme immunoassay (EIA). RESULTS: After two immunizations with LIV of seronegative individuals a 1.5 times mean increase of antibodies against homologous neuraminidase was detected (by hemagglutinin inhibition reaction). The high level of anti-neuraminidase antibodies were detected in individuals that had been naturally infected. A correlation between anti-neuraminidase IgG antibody titers obtained in EIA with whole reassortant virus A(H7N1) and purified protein was demonstrated. CONCLUSION: Modified sialidase activity inhibition method and EIA with reassortant diagnostic strain can be applied to evaluate anti-neuraminidase antibodies. PMID- 22308735 TI - [Excretion of extracellular membrane nanovesicles by aeromonas]. AB - AIM: Study of extracellular membrane nanovesicles production by Aeromonas hydrophila and Aeromonas salmonicida bacteria on a subcellular level. MATERIALS AND METHODS: 4 strains of A. hydrophila: 342-1, E 8-8, H 336 and H 1-6-05 and 1 strain of A. salmonicida A-450 as well as intact Wistar line rats were used. Methods of transmission electron microscopy: ultrathin sectioning and negative contrasting were used. RESULTS. A. hydrophila and A. salmonicida bacteria produced in pure cultures excrete into the environment extracellular membrane nanovesicles. The size of these vesicles varies from 20 to 200 nm in diameter. The process of gemmation from bacterial cell and possibility of obtaining isolated membrane nanovesicles preparations is shown. These vesicles are detected in ultrathin sections of apical surface of intact rat intestine among accumulations ofparietal microorganisms that colonize mucous membrane. Extracellular membrane nanovesicles excreted by aeromonas are analogous by size and ultrastructure to vesicles of other species of gram-negative bacteria described in the literature. CONCLUSION: During production of A. hydrophila and A. salmonicida bacteria in vitro nanovesicles are formed from the outer membranes of the cells and excreted into the environment, the nanovesicles are similar to those detected in ultrathin sections of the surface of intestine of rats among accumulations of parietal microorganisms and in glycocalix between epitheliocyte microvilli. PMID- 22308736 TI - [Analysis of pyogenic microflora structure of a cardiac surgery hospital]. AB - AIM: Long-term analysis of structure and resistance level ofpyogenic microflora in cardiac surgery hospital. MATERIALS AND METHODS: Data from microbiological studies carried out in Perm Regional Hospital No. 2 Institute of Heart from 2002 to 2010 was used. Isolation and identification of cultures was carried out by traditional methods, determination of antibiotic resistance--by disk diffusion method, sensitivity to disinfectants--by serial dilution method. RESULTS: Gram positive bacteria predominate in the structure of clinical flora--enterococci and staphylococci (aureus--during the first years of observation, coagulase negative staphylococci--later). In 2010 an increase of relative rate of gram-negative bacteria, especially pseudomonas and acinetobacters, as well as Serratia marcescens was noted. Among all microorganism species a constant increase of antibiotic resistance level was noted. Clinical microflora is highly sensitive to the preparation for final disinfection, but at the same time is characterized by the generation of resistance to the current disinfectant. CONCLUSION: Monitoring of structure and properties of clinical microflora allows to introduce correction into antibacterial therapy schemes and epidemic control measures, as well as register the emergence of hospital strains. High level of drug resistance of the flora indicates the practicability of antibiotic rotation. PMID- 22308737 TI - [Low-manifest infections with CNS damage in patients in prolonged unconscious state of non-inflammatory etiology]. AB - AIM: Study of specter of low-manifest infections (LMI) with central nervous system (CNS) damage and their role in patients in prolonged unconscious state (PUS) of noninflammatory etiology. MATERIALS AND METHODS: 32 patients (23 male, 9 female; age 14-58) in PUS of various etiology were examined. The main group (18 patients) received therapy against all infectious diseases including LMI; control group (14 patients)--only against common and nosocomial microflora. Patients were immunologically, infectologically and neurologically examined in dynamic. The data obtained were treated by using STATISTICA for Windows (version 5.5). RESULTS: Significant differences in immune and infectologic status depending on the nature of primary CNS damage were not detected. Immunodeficiency was detected in all patients; 94% of patients had increased non-specific IgM and IgE. Among LMI agents Chlamydia spp. were predominant. Cultural and/or PCR methods detected this microorganism during the primary examination in cerebrospinal fluid samples in 56% patients and in blood samples in 56%; during the second diagnostics or autopsy--only in 13 and 25%, respectively. Detection of Bacteroides fragilis, Human Herpes Virus (HHV-6), Virus Epstein Barr (VEB), Cytomegalovirus (CMV) in cerebrospinal fluid, blood and on mucous membranes of nasopharynx and conjunctiva was grouped more frequently with the presence of Chlamydia spp. in the CNS (p < 0.05) than with other LMI agents. Sanation of CNS from LMI was significantly accompanied by regeneration of communicative activity in comparison with the control group. CONCLUSION: In patients with PUS high frequency of CNS infection by various LMI agents and primarily Chlamydia spp. should be considered. Sanation from LMI can become a "window" for effective neuro-regenerative treatment. PMID- 22308738 TI - [Isolation and characterization of vaginal lactobacilli producing hydrogen peroxide]. AB - AIM: Isolation and characteristics of vaginal lactobacilli that actively generate H2O2 and have high antagonistic activity. MATERIALS AND METHODS: Staphylococcus aureus 8956, Escherichia coli 8852, Klebsiella pneumoniae 8795 and Candida albicans 5646 were used as target-strains. Skim milk and MRS medium were used for lactobacilli isolation and cultivation. Antagonism was studied in complete agar and Saburo medium. Merckoquant peroxide test (Merck) stripes were used for the determination of H2O2. Antibacterial activity was determined by diffusion into agar. Specific culture growth rate was determined by conventional method, acidification of the culture medium--by pH-meter. RESULTS: 12 strains were isolated from vaginal smears of healthy women. These strains have an ability to ferment milk among which a highly active H2O2 producer was isolated and attributed to Lactobacillus delbrueckii by the results of 16S rRNA and alpha subunit RNA polymerase gene sequence analysis (16S rDNA and rpoA genes are registered in GenBank, numbers HQ379171 and HQ379180 respectively). L. delbrueckii MH-10 bacterial cells were characterized by specific growth speed 1.26 per hour, reaching a maximum titer of 2 x 10(9) PFU/ml with lowering medium pH to 4.0. Under aerated conditions H2O2 concentration reached 100 microg/ml or more. L. delbrueckii MH-10 has high antibacterial activity against S. aureus, E. coli, K. pneumoniae. CONCLUSION: L. delbrueckii MH-10 isolate is an active H2O2 producer, has high growth speed and broad antibacterial activity spectrum, is a perspective candidate for the development of probiotic preparation for the prophylaxis and therapy of vaginoses. PMID- 22308739 TI - [Features of microbiocenosis composition of large intestine of humans with various degree of local metabolic disorders]. AB - AIM: Detection of features of qualitative and quantitative composition of large intestine microbiocenosis of humans with various degree of local metabolic disorders during dysbacterioses due to various causes. MATERIALS AND METHODS: Microflora of large intestine and content of malonic dialdehyde (MDA) in coprofiltrates of 330 adult humans with large intestine dysbacterioses due to various causes were studied. RESULTS: It was established, that high MDA content in coprofiltrates matches higher quantities of opportunistic microorganisms and atypical escherichia in microflora composition of large intestine. Relation of MDA composition in coprofiltrates and factors that cause dysbacteriosis were not detected. CONCLUSION: The studies performed give evidence that changes in local metabolic activity may be a single mechanism of development of large intestine dysbacterioses that are caused by various factors. PMID- 22308740 TI - [HIV infection epidemic in Russian Federation and its features at the present stage]. AB - The problem of HIV infection spread in Russian Federation is examined in the article. Data on HIV infection dynamics and predominate risk groups of the population during different years are presented. Age structure of HIV infected individuals in Russian Federation is examined. Main factors that promote HIV infection spread in Russian Federation are specified and means of control are proposed. PMID- 22308741 TI - [Significance of nervous system in inflammatory disease of the gut]. AB - The review is dedicated to the role of sensory nerve endings of the gut, vegetal and central nervous system (CNS) in the diseases of gastrointestinal tract. Molecular-cellular inter-relations of nerve endings of the gut and neurons of the CNS are a key axis that among with neuroendocrine and immune responses, define the clinical manifestation and rehabilitation potential of the patient in the development of infectious process in the gut. Infectious-inflammation processes in the gut of various etiologies promote the increase of permeability of the intestine barrier with consequent trans-intestinal translocation of toxins and molecular mediators of inflammation to the system bloodstream. Bacterial toxins including LPS and cytokine imbalance induce microglia damage that defines destabilization of the barrier and vulnerability of neurons. The consequence is the inadequate reaction from autonomous nervous system with the development of uncontrolled abdominal spasms and increasing muscular atrophy. Toxemia at the same time promotes the increase of hematoencephalic barrier permeability, intake of inflammatory cytokines into the brain that induce inflammation in the brain periventricular areas with the development of intestinal encephalopathy. The assumed pathogenetic mechanism dictates a new therapy strategy that is mainly directed at brain protection: administration of etiotropic and anti-inflammatory drags, myotropic spasmolytics and various neuroprotectors. PMID- 22308742 TI - [Pneumococcal surface protein A and new approaches for pneumococcal vaccine development]. AB - The problem of pneumococcal infections is pressing for the whole world. Existing vaccines based only on pneumococci polysaccharide antigens or polysaccharide antigens and diphtherial anatoxin are not capable of protecting from all serotypes of the microorganism. Reasonability of creation of pneumococcal vaccine based on surface proteins of Streptococcus pneumoniae is discussed in the literature. One of such key pneumococcal proteins is pneumococcal surface protein A (PSPA), because it is detected in all the S. pneumoniae strains, has cross activity and switches B-cell immune response to T-cell. Currently the development of conjugated vaccine based on surface proteins and capsule polysaccharides of pneumococcus seems promising. PMID- 22308743 TI - [Development of vaccine preparation for urogenital Chlamydiosis prophylaxis]. AB - Chlamydia trachomatis is one of the most widespread bacterial pathogens in the world that is transmitted sexually. Thereby a development of vaccine preparation for therapy and prophylaxis of infections caused by C. trachomatis is an actual topic of scientific research across the entire world. These vaccines could be used for both prophylaxis and therapy of already established chlamydia infection and, respectively, reduce the risk of chronic condition and prevent the spread of pathogen in the population. Features of chlamydia biology that are associated with obligate intracellular parasitism and immunopathologic state induced by this agent significantly complicate developments in this field. Currently a vaccine preparation that has reached clinical trials does not exist. PMID- 22308744 TI - [Nutrient medium for isolation and cultivation of bifidobacteria]. PMID- 22308745 TI - [Biological activity of native and modified lipopolysaccharides Rahnella aquatilis]. AB - The results of the comparative toxicity studies of native lipopolysaccharide (LPS) of Rahnella aquatilis 96U037 and that modified by tin complexes indicates that, due to the modification of LPS by tin complex with benzoylhydrazone of 4 dimethylaminobenzaldehyde, a decrease of its toxicity was observed that led to disappearance of the pyrogenic effect. All obtained derivatives lost completely the antigenic activity both in homologous and heterologous systems which may indicate to the interaction of modifying complexes with certain groups being the components of antigenic determinant. The paper is presented in Ukrainian. PMID- 22308746 TI - [Influence of metal nanoparticles on some microorganisms and microflora of unpasteurized beer]. AB - The influence of nanoparticles of gold, silver, dioxide of cerium and zirconium in low concentration (0.5-7.5 mg/l) on pure cultures of Escherichia coli IEM-1, Bacillus subtilis BT-2, Candida scottii KB-2, Saccharomyces cerevisiae OB-3, Aspergillus niger R-3, Fusarium culmorum T-7 and Penicillium chrysogenum F-7 has been investigated. Silver nanoparticles, which caused a decrease of the amount of S. cerevisiae OB-3 cells by 90% after one hour of exposition, and led to almost complete death of vegetative and spore cells of B. subtilis BT-2 after 1 and 24 h of exposition, respectively, proved to be the most effective antimicrobial preparation. The decrease by one-two orders of the amount of B. subtilis BT-2 and of S cerevisiae OB-3 cells under the influence of preparations of silver nanoparicles in the presence of gold has been established. After adding silver preparations to the unpasteurized beer one could observe a decrease by 10-20% of bacterial and by about 40% of fungi which contaminated microflora on the 20th day of shelf-life. The paper is presented in Ukrainian. PMID- 22308747 TI - [Phylogenetic analysis of lupine's bacterial wet rot--"Pseudomonas xanthochlora"]. AB - The sequencing of 16S rRNA gene nucleotide chain of the 12 "P. xanthochlora" strains, collection Pseudomonas marginalis 8572 strain and Pseudomonas marginalis pv. marginalis 9175T P. fluorescens B-17T typical strains has been determined. The analysis of the 16S rRNA gene nucleotide chain showed high level of homology (98-99%) of "P. xanthochlora" investigated strains with the same of representatives of both P. fluorescens and P. marginalis species. PMID- 22308748 TI - [Growth peculiarities of probiotic strains of Bacillus subtilis at their joint cultivation in deep conditions]. AB - Growth peculiarities of probiotic strains B. subtilis UKM 5139 and B. subtilis UKM 5140 have been studied at their joint cultivation in deep conditions. It has been shown that in such conditions of cultivation the growth of bacilli and the accumulation of biomass of the cells that possessed high antagonist properties have been intensified. The mixed culture grown when the medium was inoculated by the strains B. subtilis UKM 5139 and B. subtilis UKM 5140 with the ratio of 1:2 was distinguished by the highest specific growth rate. Applicability of synthetic and complex media both for separate and joint cultivation of bacilli has been shown. PMID- 22308749 TI - [Obtaining and characteristic of Streptomyces globisporus 1912 mutants with high biosynthesis of landomycin e]. AB - Eight highly productive UV-induced mutants of Streptomyces globisporus 1912 with high biosynthesis of landomycin E were isolated, their isolation frequency being 2 x 10(-3). Mutants 1-1, 1-4-1, 1-1y, 1-2y, 4-1, 1-2 produced 175-187.5 mg of landomycine E and 1-1b, 4-1-1 and 1-3--80-100 mg per 1 liter of soybean agar after 48 hours of cultivation The mutant 4-1-1 had the highest antibiotic activity and middle level of landomycin E production. PMID- 22308750 TI - [Damage of modern building materials by microscopic fungi]. AB - Resistance of three materials, produced on the basis of concrete compounds to the action of microscopic fungi, isolated from damaged living buildings, has been first investigated. It has been shown that samples of froth-block and thermoeffective block had low fungal resistance, in contrast to samples of cellular polystyrene concrete, which were resistant to fungal action, that can be associated with peculiarities of their component composition. PMID- 22308751 TI - [AntiEBV activity of 6-azacytidine and its derivatives]. AB - Epstein-Barr virus (EBV) causes several lymphoproliferative diseases, lesions of the central and peripheral nervous systems. Spectrum of etiotropic medicines against EBV is limited. The paper presents the anti-virus research of modified nucleoside with a wide spectrum of action - 6-azacytidine and its derivatives (2' 3'-seco-5-methyl-6-AC, 2',3'-dideoxy-2',3'-didehydro-6-AC and 2'-deoxy-6-AC) on the model of Epstein-Barr virus in Raji lymphoblastoid cells. Parameters of cytotoxicity (CC,) for the investigated substances were determined which amounted to 120 microg/ml, 180 microg/ml, 500 microg/ml, 330 microg/ml, and the effective concentration (ECU)--0.5 microg/ml. 1 microg/ml, 4 microg/ml, 11 microg/ml, in accordance with the sequence of preparations listed above. The results indicate a high antiEBV activity since their selectivity indexes (SI) were 240, 180, 125, 30 that is 1.3-10 times higher than the reference substance acycloguanosine. Apoptosis-stimulating action of 6-azacytidine and its derivatives was revealed. An increase of percentage of apoptotic cells in EBV-infected Raji cells and those treated with investigated substances as compared to uninfected ones was observed after 24 hours. Thus, our results provide new biological properties of the azacytidine substances. PMID- 22308752 TI - [Toxic and mutagenic influence of hexachlorocyclohexane and its microbial destruction products on soil microbial cenosis]. AB - Microbial strains Pseudomonas putida 9, Stenotrophomonas maltophilia IMV B-7288 destructed hexachlorcyclohexane (HCH) isomers complex by 31.1-76.6 and 30.7 73.2%. respectively, in comparison with given level. HCH and its destruction intermediates had toxic and mutagenic influence on soil microbial associations decreasing their survival to 6.9-21.7%. The investigated destruction products and intermediates obtained by Pseudomonas putida 9, Stenotrophomonas maltophilia IMV B-7288 have demonstrated weak mutagenic properties. The use of cultures destructors opens the prospects for application of the mentioned strains as the components of microbial biopreparations for remediation of polluted soils. The use of soil microbial cenosis as the test-system for ecotoxicological assessment permitted to obtain more detailed pattern of toxic and mutagenic properties of HCH and products of its destruction. PMID- 22308753 TI - [Detection of bacteriophages of siphoviridae family in Erwinia carotovora subsp. carotovora]. AB - It was established that the polylysogenic phage system of culture Erwinia carotovora subsp. carotovora 91P includes: a) defective bacteriophages of Myoviridae family, which are displayed as macromolecular carotovoricins b) valuable highly unstable temperate phage, which can be attributed to the family Myoviridae, and which, perhaps, is an analogue of phage ZF40 [6], and c) resistant to osmotic shock temperate phage of family Siphoviridae. This phage, called TIRI, consists of isometric head 50 nm in diameter and a rigid tail structure 203 nm long. A characteristic feature of the phage tail is an evident transverse striation, which is also indicative for the tail-like particle of the defective temperate phage of the strain 48A-7/4b. In general, the phage system of E carotovora subsp. carotovora is similar to Pseudomonas aeruginosa with its R- and F-bacteriocins, and phages of the families Myoviridae and Siphoviridae. PMID- 22308754 TI - [Effect of structural P-protein of potato curly dwarf virus on replicase activity of mRNP-complexes of infected plants]. AB - All representatives of rhabdoviruses contain a nucleocapside phosphoprotein - P protein which is an essential subunit of the viral RNA-dependent RNA polymerase complex. As a result of studying the effect of nucleocapside protein P(NS) on replicase activity of mRNP isolated from plants infected by potato curly dwarf virus in the system in vitro, it was established that nucleocapside P-protein stimulates considerably the replicase activity of membrane-bound polysomal m-RNP P-protein being available in concentration of 15 microg/ml in the replication system in vitro of membrane-bound polysomal mRNP, the replicase activity increased 11.7 times. This property of nucleocapside P-protein at the same concentration was displayed to a less extent with the presence of free polysomal mRNP, in the system in vitro. Thus the replicase activity mRNP-complexes in the replication system in vitro depends on the presence of nucleocapside viral P protein in the system. Its concentration being increased or decreased, one can observe the change of the replicase activity. PMID- 22308755 TI - The cylindrospermopsin alkaloids. PMID- 22308756 TI - The pyrrolo[2,1-a]isoquinoline alkaloids. AB - The present chapter describes isolation, biogenetic proposals, and syntheses of the natural products 1-4 and 10-11 with a pyrrolo[2,1-a]-isoquinoline framework. Moreover, the syntheses of some structural analogs are discussed. The pyrrolo[2,1 a]isoquinolines are of interest due to their promising biological activities. For crispine A (1), many total syntheses have been reported and for trolline (3), only three. Only one total synthesis has been reported for each of the following natural products: peyoglutam (10), mescalotam (11), and the antitumor active crispine B (2). Some of the pyrrolo[2,1-a]isoquinoline alkaloids have not been synthesized yet. The following three tables summarize the synthetic efforts toward crispine A (1) (Table 1: racemic syntheses; Table 2: enantioselective syntheses) and trolline (3) (Table 3). PMID- 22308757 TI - Intentional inferences are not more likely than unintentional ones: some evidence against the intentionality bias hypothesis. AB - We conducted a study to test the hypothesis that inferences about intentionality are biased toward an intentional interpretation. Contrary to previous research, participants were no more likely to judge ambiguous actions as intentional in a speeded compared to an unspeeded condition. Further, participants were faster to respond and more consistent in responding to unintentional rather than intentional actions. PMID- 22308758 TI - Output order reflects the cognitive accessibility of goals. AB - Goal accessibility--the ease or speed with which a goal is activated--increases the likelihood that it will be acted on. The present studies validate output order as a measure of goal accessibility that can be applied to goal lists in both laboratory and naturalistic settings. In three studies, output order (the order in which goals are listed in a free-response format) was related to self reported goal value but was not redundant with it. Furthermore, output order was affected by motivational priming whereas value was not, and order associated with typical student goals (e.g., achievement) compared with atypical goals (e.g., power). Output order is well suited to bring the study of accessibility to naturalistic studies of goals and goal pursuit. PMID- 22308759 TI - The shared leadership process in decision-making teams. AB - The present study examined the process of shared leadership in 45 ad hoc decision making teams. Each team member's leadership behavior (n = 180) was assessed by behaviorally coding videotapes of the teams' discussions. The within-team patterns of leadership behavior were examined using cluster analysis. Results indicated that the likelihood of a team experiencing a full range of leadership behavior increased to the extent that multiple team members shared leadership, and that teams with shared leadership experienced less conflict, greater consensus, and higher intragroup trust and cohesion than teams without shared leadership. This study supports previous findings that shared leadership contributes to overall team functioning, and begins to delineate the extent to which team members may naturally share leadership. PMID- 22308760 TI - Materialism, status consumption, and consumer independence. AB - Materialism influences many people. We focus on two aspects of this influence: reactions to prestige products and to the influence of others. A study of 187 U.S. student consumers shows that materialism is positively related to buying products that confer status. In contrast, materialism is negatively related to consumer independence, an enduring tendency to pay minimal attention to the prescribed norms of other consumers and to make product and brand decisions according to personal preferences. Consuming products for status is also negatively related to consumer independence. Moreover, the association between materialism and consumer independence is completely mediated by consuming for status. Materialism urges consumers to be status conscious so that they follow social norms in purchasing, but seeking status through goods is avoided by less materialistic, independent consumers. A second study (n = 258) also using student consumers confirmed these results. PMID- 22308761 TI - Hungry for love: the influence of self-regulation on infidelity. AB - The current research examines the effect of self-regulation on the likelihood of committing infidelity. Thirty-two college students in exclusive romantic relationships interacted through a private chat room with an opposite-sex confederate. Prior to this interaction, a food-restriction task depleted half the participants of self-control. As predicted, depleted levels of self-regulation increased the likelihood of infidelity. Specifically, depleted participants were more likely to both accept a coffee date from and supply a personal telephone number to the confederate than non-depleted participants. Weakened self-control may be one potential cause for the levels of infidelity occurring in romantic partnerships today. PMID- 22308762 TI - Television and aggression: a test of a mediated model with a sample of Portuguese students. AB - We examined the role of identification with violent TV heroes, enjoyment of TV violence, and perceived reality in TV violence as mediators of the relationship between viewing TV violence and subsequent physical and verbal aggression. A sample of 722 4th, 6th, and 8th grade students from schools in the central region of Portugal completed measures assessing enjoyment of TV violence, perceived reality, aggression, identification with violent TV heroes, and exposure to TV violence. The results showed that the relationship between TV violence and physical aggression is mediated by enjoyment of TV violence, perceived reality in TV violence, and identification with violent TV heroes. The TV violence to verbal aggression relationship was also mediated by enjoyment of TV violence. PMID- 22308763 TI - Self-stereotyping: the central role of an ingroup threatening identity. AB - Self-stereotyping is a process by which people belonging to a stigmatized social group tend to describe themselves more with stereotypical traits as compared with traits irrelevant to the ingroup stereotype. The present work analyzes why especially members of low-status groups are more inclined to self-stereotype compared to members of high-status groups. We tested the hypothesis that belonging to a low-, rather than a high-status group, makes low-status members feel more threatened and motivates them to protect their self-perception by increasing their similarity with the ingroup. Specifically, we investigated the effects of an experimental manipulation that was conceived to either threaten or protect the natural group membership of participants from either a low- or a high status group on the level of self-stereotyping. The findings supported the idea that only low-status group members protected themselves when their group identity was threatened through increased self-stereotyping. PMID- 22308764 TI - Predicting right-wing authoritarianism via personality and dangerous world beliefs: direct, indirect, and interactive effects. AB - In an Italian sample (N = 483, 78.23% women, mean age = 27.61 years old), we used structural equation modeling with latent variables and interactions to analyze the direct, indirect, and interactive effects exerted on right-wing authoritarianism by the Big Five factors of personality and by dangerous world beliefs. Openness, Neuroticism, and Conscientiousness exerted direct effects on right-wing authoritarianism; the first two relationships were partially mediated by dangerous world beliefs. Most importantly, the relationship between dangerous world beliefs and right-wing authoritarianism was moderated by Openness: dangerous world beliefs significantly influenced right-wing authoritarianism solely for participants high in Openness. Limitations and possible developments of this research are discussed. PMID- 22308765 TI - Sampling flies or sampling flaws? Experimental design and inference strength in forensic entomology. AB - Forensic entomology is an inferential science because postmortem interval estimates are based on the extrapolation of results obtained in field or laboratory settings. Although enormous gains in scientific understanding and methodological practice have been made in forensic entomology over the last few decades, a majority of the field studies we reviewed do not meet the standards for inference, which are 1) adequate replication, 2) independence of experimental units, and 3) experimental conditions that capture a representative range of natural variability. Using a mock case-study approach, we identify design flaws in field and lab experiments and suggest methodological solutions for increasing inference strength that can inform future casework. Suggestions for improving data reporting in future field studies are also proposed. PMID- 22308766 TI - What do we need to know about disease ecology to prevent Lyme disease in the northeastern United States? AB - Lyme disease is the most commonly reported vector-borne disease in the United States, with the majority of cases occurring in the Northeast. It has now been three decades since the etiological agent of the disease in North America, the spirochete Borrelia burgdorferi, and its primary North American vectors, the ticks Ixodes scapularis Say and I. pacificus Cooley & Kohls, were identified. Great strides have been made in our understanding of the ecology of the vectors and disease agent, and this knowledge has been used to design a wide range of prevention and control strategies. However, despite these advances, the number of Lyme disease cases have steadily increased. In this article, we assess potential reasons for the continued lack of success in prevention and control of Lyme disease in the northeastern United States, and identify conceptual areas where additional knowledge could be used to improve Lyme disease prevention and control strategies. Some of these areas include: 1) identifying critical host infestation rates required to maintain enzootic transmission of B. burgdorferi, 2) understanding how habitat diversity and forest fragmentation impacts acarological risk of exposure to B. burgdorferi and the ability of interventions to reduce risk, 3) quantifying the epidemiological outcomes of interventions focusing on ticks or vertebrate reservoirs, and 4) refining knowledge of how human behavior influences Lyme disease risk and identifying barriers to the adoption of personal protective measures and environmental tick management. PMID- 22308767 TI - A new species of Tunga (Siphonaptera: Tungidae) from Brazil with a key to the adult species and neosomes. AB - Tunga bossii new species of tungid sand flea belonging to the caecata group is described with illustrations of the adult female, parasitizing the wild rodent Delomys dorsalis (Hensel) from Brazilian Atlantic Forest. Tunga bossii differs from the ten other known species of Tunginae by the size of the first segment of the maxillary palp and the presence of two bristles at the base of the maxilla. Tunga bossii also can be differentiated from other species of the T. caecata group by the eye morphology. A key to the adult species and neosomes of the genus Tunga also is included. PMID- 22308768 TI - Field sampling rate of BG-sentinel traps for Aedes aegypti (Diptera: Culicidae) in suburban Cairns, Australia. AB - Mini-mark-release-recapture experiments were conducted in suburban Cairns, Australia to establish the sampling rate of the Biogents-Sentinel (BGS) trap for adult Aedes aegypti (L.). Small cohorts of marked mosquitoes (30 females and 15 males) were released at typical Cairns residences, and the number of marked mosquitoes recaptured in the BGS trap after 24 h was recorded. The sampling rate was compared between two seasons and two common housing styles (high-set 'Queenslander-style' timber and low-set brick houses), between old gravid and young nulliparous females, and between mosquitoes released in different areas of a house. Overall, the BGS traps recaptured a mean (+/- SEM) of 24.6% (+/- 1.9) of the released marked female mosquitoes in 24 h. The mean recapture rate for females was significantly higher in the dry season (30.4% +/- 2.8) compared with the wet (18.8% +/- 2.2). The overall recapture rates did not differ significantly between the two house types, but variability between the individual premises was high. An overall mean of 18.2% (+/- 1.7) of males was collected. Recapture rates of young nullipars and older gravid females were similar. These recapture rates can be used to estimate the population density of Ae. aegypti females in north Queensland, although it will provide an underestimate as trap sample was largely representative of mosquitoes present in the same area as the trap, and not from other areas of the house. PMID- 22308769 TI - Dispersal of Culex mosquitoes (Diptera: Culicidae) from a wastewater treatment facility. AB - A mark-recapture project examined dispersal and flight distances of Culex mosquitoes from a wastewater treatment plant in Albany, NY, during 2007 and 2008. A self-marking device was constructed to mark egressing mosquitoes with fluorescent marking powder. Mosquitoes were recaptured using 30 CDC miniature light traps located within a 2.0 km radius of the marking site. A total of 13 and 10 marked Culex mosquitoes were recaptured in 2007 and 2008, respectively. Culex mosquitoes traveled a minimum of 0.16 km, a maximum of 1.98 km and, following correction for decreasing trap density with distance, had a mean distance traveled of 1.33 km. Characterizing the dispersal patterns of these mosquitoes is important for understanding the distribution of West Nile virus and other pathogens. PMID- 22308770 TI - Ecological aspects of phlebotomines (Diptera: Psychodidae) in endemic area of visceral leishmaniasis, Campo Grande, State of Mato Grosso do Sul, Brazil. AB - Aspects of phlebotomine behavior were investigated in the city of Campo Grande, Mato Grosso do Sul state. The insects were captured weekly during December 2003 to November 2005, with Centers for Disease Control light traps at seven different sites including forests and residential areas. In total, 11,024 specimens (7,805 males and 3,219 females) were collected, from which 9,963 (90.38%) were identified as Lutzomyia longipalpis, the proven vector of American visceral leishmaniasis agent. The remaining 9.62% comprised 21 species. L. longipalpis was the most frequent species in all sampled sites, and the first in the ranking of standardized species abundance index. In residential areas this species clearly predominated in the peridomicile (90.96%), in contrast to the intradomicile (9.04%); in animal shelters, it was more numerous in hen houses and prevailed at ground level, inside, and at forest edge around the residences; this aspect is worrying because this insect may remain sheltered in forested environments during the use of insecticides in homes. In the forest environment, other probable or proven vector of cutaneous leishmaniasis agents were also captured such as Lutzomyia whitmani (=Nyssomyia whitmani, sensu Galati), Lutzomyia antunesi (=Nyssomyia antunesi, sensu Galati), and Lutzomyia flaviscutellata (=Bichromomyia flaviscutellata, sensu Galati). PMID- 22308771 TI - Monitoring temporal abundance and spatial distribution of Aedes polynesiensis using BG-Sentinel traps in neighboring habitats on Raiatea, Society Archipelago, French Polynesia. AB - Adult numbers and sizes of mosquitoes were monitored for 2 yr in neighboring habitats on the western coast of Raiatea (Society Archipelago) in anticipation of testing new vector control technologies. Aedes polynesiensis Marks females comprised the overwhelming majority (approximately 99%) of the three species of mosquitoes captured in Biogent Sentinel traps placed at fixed sites on three small satellite islands (motus) of the western lagoon and on the shoreline of Raiatea. Aedes polynesiensis males, Aedes aegypti (L.), and Culex quinquefasciatus Say rarely were collected. Numbers of Ae. polynesiensis females per collection differed among trapping dates and locations, with the majority of females captured on two motus, Horea and Toamaro. Shoreline and Horea females had significantly longer mean wing lengths than females from Tiano and Toamaro. Thus, wing lengths were influenced more by local developmental conditions than overall numbers of adults. Significantly more females were captured during the wet season than the dry season. Nonetheless, at least on the two highly productive motus, dry-season females had larger wing lengths than their wet season counterparts. Local weather patterns predicted about half the variation in mosquito numbers. Differences in vector abundance observed when comparing neighboring motus are likely because of differences in human activity and mosquito suppression. PMID- 22308772 TI - Evaluation of a stable isotope method to mark naturally-breeding larval mosquitoes for adult dispersal studies. AB - Understanding mosquito dispersal is critically important for vector-borne disease control and prevention. Mark-release-recapture methods using various marking techniques have made substantial contributions to the study of mosquito biology. However, the ability to mark naturally breeding mosquitoes noninvasively and with life-long retention has remained problematic. Here, we describe a method to mark naturally breeding mosquitoes with stable isotopes. Culex pipiens f. molestus mosquitoes were provisioned as larvae in laboratory experiments with 15N-labeled potassium nitrate and 13C-labeled glucose. Larval enrichment was sufficient to differentiate marked adult mosquitoes from unmarked control mosquitoes and the natural source population from Chicago Illinois, using either delta 15N or delta 13C. Isotopic retention lasted for at least 55 d for adult male and females mosquitoes. There were no consistent effects of isotopic enrichment on immature mosquito survival or adult mosquito body size. We then applied this marking technique to naturally breeding Culex pipiens mosquitoes in suburban Chicago, IL, and for the first time, report successful isotopic enrichment of mosquitoes in the field. This stable isotope marking technique will facilitate studies of mosquito dispersal. PMID- 22308773 TI - Water surface area and depth determine oviposition choice in Aedes albopictus (Diptera: Culicidae). AB - Oviposition choice is a well-studied aspect of the mosquito life cycle, and offers a potential avenue for species-specific surveillance and control. In container inhabiting mosquitoes, there has been a focus on how the components of the aquatic media determine choice, with little work on the physical characteristics of the containers themselves. We performed five experiments examining the effect of physical container parameters on oviposition choice by Aedes albopictus. We examined containers of three different surface areas (small, 496 cm2; medium, 863 cm2; and large, 1,938 cm2) at the same water depth and the same or different heights in a series of binary choice assays. We also examined different depths with the same surface area in clear containers (where the depth may be perceived by the darkness of the water) and in opaque containers, which appear uniformly dark at different depths. We found a significant preference for medium containers over large containers, whether the containers were different or the same heights, and a trend toward a preference for small containers over medium containers. There was a preference for deeper water regardless of whether containers were clear or opaque. These behaviors suggest mosquitoes take into account physical aspects of their habitats and their oviposition choices are consistent with minimizing the risk of habitat drying. PMID- 22308774 TI - The population structure of Lutzomyia verrucarum (Diptera: Psycodidae), a Bartonella bacilliformis and Leishmania peruviana vector in Peru. AB - The population genetic structure of Lutzomyia verrucarum (Townsend), a sand fly disease vector of Carrion's disease and cutaneous leishmaniasis in the Peruvian Andes, was characterized by sequencing 653 bp of cytochrome b and 1,125 bp of the NADH dehydrogenase subunit 4 genes of its mitochondrial genome. DNA sequence variation within and between valleys was compared in a sample of 220 sand flies from three valleys (Purisima, Huaylas, and Conchucos) and five departments (Amazonas, Cajamarca, Piura, Lima, and Huancavelica). Gene network and phylogenetic analyses indicated a high similarity of haplotypes collected within a single valley (0-0.52% nucleotide divergence). Flies from each valley had unique genotypes not shared with specimens from other valleys or from more distant regions (0.8-3.1% nucleotide divergence). Mountain ranges and geographic distance appear to have impeded migration (N(m) = < 0.18) between valleys and separated populations into discrete genetic units. PMID- 22308775 TI - Microsatellite-based parentage analysis of Aedes aegypti (Diptera: Culicidae) using nonlethal DNA sampling. AB - To track Aedes aegypti (L.) egg-laying behavior in the field in Iquitos, Peru, we developed methods for 1) sampling DNA from live mosquitoes and 2) high through put parentage analysis using microsatellite markers. We were able to amplify DNA extracted from a single hind leg, but not from the pupal exuvia. Removal of a leg from teneral females caused no significant changes in female behavioral or life history traits (e.g., longevity, blood feeding frequency, fecundity, egg hatch rate, gonotrophic cycle length, or oviposition behavior). Using a panel of nine microsatellite markers and an exclusion-based software program, we matched offspring to parental pairs in 10 Ae. aegypti test families in which parents originated from natural development sites in Iquitos. By mating known individuals in the laboratory, retaining the male, sampling the female's DNA before release, and collecting offspring in the field, the technique we developed can be used to genotype large numbers of Ae. aegypti, reconstruct family relationships, and track the egg-laying behavior of individual Ae. aegypti in nature. PMID- 22308776 TI - Behavioral and physiological response of Musca domestica to colored visual targets. AB - A better understanding of the visual attraction of house flies to colors and patterns is needed to improve fly trap performance. This study combined physiological responses measured with electroretinogram studies of the house fly's compound eyes and ocelli with behavioral attraction of flies to reflective colors and patterns in light tunnel assays. Compound eye and ocellar electroretinogram responses to reflected light were similar, with the largest responses to white and blue followed by yellow, red, green, and black. However, data from light tunnel behavioral assays showed that flies were attracted to white and blue light but were repelled by yellow. The addition of a black line pattern enhanced the attractiveness of blue visual targets, whereas yellow lines decreased attractiveness. Sensory input from the compound eye and the ocellus seems to be integrated to direct fly behavior. There is a direct correlation of house fly attractiveness to visual targets and the intensity of electrophysiological response, except for the yellow targets, which repel flies despite of intense electrophysiological response. PMID- 22308777 TI - Efficacy of plant-derived and synthetic compounds on clothing as repellents against Ixodes scapularis and Amblyomma americanum (Acari: Ixodidae). AB - We conducted field trials to compare the relative repellent activity of two natural product compounds (nootkatone and carvacrol) with commercially available plant-derived (EcoSMART organic insect repellent) and permethrin-based (Repel Permanone) repellents against adult Ixodes scapularis Say and Amblyomma americanum (L.) (Acari: Ixodidae) by using treated coveralls. One day after treatment, nootkatone and carvacrol provided 100% repellency of I. scapularis adults, with nootkatone maintaining complete protection through 3 d, whereas carvacrol showed steadily declining repellency against I. scapularis during the 7 d course of the trials. Nootkatone was at least as effective against host-seeking A. americanum as against I. scapularis through 3 d. Carvacrol provided little protection against A. americanum adults. Both natural compounds performed well initially in comparison with the commercial products. After 7 d, nootkatone was the most effective against both species followed in order of activity by Permanone, EcoSMART, and carvacrol. Nootkatone seems to have offer considerable potential as a clothing repellent against both I. scapularis and A. americanum. PMID- 22308778 TI - Enhanced toxicity of binary mixtures of larvicidal constituents from Asarum heterotropoides root to Culex pipiens pallens (Diptera: Culicidae). AB - The toxicity of pellitorine alone or in combination with (-)-asarinin, alpha asarone, methyleugenol, or pentadecane (1:1, 1:2, 1:3, 2:1, and 3:1 ratios) to third instars from an insecticide-susceptible KS-CP strain and -resistant DJ-CP colony of Culex pipiens pallens Coquillett was evaluated using a direct-contact mortality bioassay. The binary mixture of pellitorine and (-)-asarinin (3:1 ratio) was significantly more toxic against KS-CP larvae (0.95 mg/liter) and DJ CP larvae (1.07 mg/liter) than either pellitorine (2.08 mg/liter for KS-CP and 2.33 mg/liter for DJ-CP) or (-)-asarinin (11.45 and 12.61 mg/liter) alone. The toxicity of the other binary mixtures (1:1, 1:2, 1:3, and 2:1 ratios) and pellitorine did not differ significantly from each other. Based on the co toxicity coefficient (CC) and synergistic factor (SF), the three binary mixtures (1:3, 2:1, and 3:1) operated synergistically (CC, 250-390 and SF, 1.4-2.2 for KS CP; CC, 257-279 and SF, 1.1-2.1 for DJ-CP). The binary mixtures of pellitorine and (-)-asarinin merit further study as potential larvicides for the control of insecticide-resistant mosquito populations. PMID- 22308779 TI - Collection of Culicoides (Diptera: Ceratopogonidae) using CO2 and enantiomers of 1-octen-3-ol in the United Kingdom. AB - The host kairomones carbon dioxide (CO2) and 1-octen-3-ol elicit a host seeking response in a wide range of haematophagous Diptera. This study investigates the response of Culicoides biting midges (Diptera: Ceratopogonidae) to these cues using field-based experiments at two sites in the United Kingdom with very different species complements. Traps used for surveillance (miniature CDC model 512) and control (Mosquito Magnet Pro) were modified to release ratios of (R)- and (S)-1-octen-3-ol enantiomers in combination with CO2 and, in the case of the latter trap type, a thermal cue. Abundance and species diversity were then compared between these treatments and against collections made using a trap with a CO2 lure only, in a Latin square design. In both habitats, results demonstrated that semiochemical lures containing a high proportion of the (R)-enantiomer consistently attracted a greater abundance of host-seeking Culicoides females than any other treatment. Culicoides collected using an optimal stimulus of 500 ml/min CO2 combined with 4.1 mg/h (R)-1-octen-3-ol were then compared with those collected on sheep through the use of a drop trap. While preliminary in nature, this trial indicated Culicoides species complements are similar between collections made using the drop trap in comparison to the semiochemical-baited CDC trap, and that there are advantages in using (R)-1-octen-3-ol. PMID- 22308780 TI - Mechanisms underlying fipronil resistance in a multiresistant field strain of the German cockroach (Blattodea: Blattellidae). AB - German cockroaches (Blattella germanica L.) have significant impacts on human health, most notably they are implicated as causes of childhood asthma. Gel bait formulations of fipronil, a phenylpyrazole insecticide, have been in use for German cockroach control in the United States since 1998. Previously, dieldrin resistant German cockroach strains were shown to have 7- to 17-fold cross resistance to fipronil. More recently, a field-collected strain (GNV-R) displayed approximately 36-fold resistance to topically applied fipronil at the LD50 level, which is the highest level of fipronil resistance reported to date in the German cockroach. The aim of the current research was to identify mechanism(s) responsible for high-level fipronil resistance in the GNV-R strain. Synergist bioassays conducted using topical and injection application methods implicated cytochrome P450-mediated detoxification in resistance. Electrophysiological recordings using the suction-electrode technique revealed the nervous system of the GNV-R strain is insensitive to fipronil. In agreement with electrophysiology results, the alanine to serine (A302S) mutation encoded by the gamma-amino butyric acid-gated chloride channel subunit gene resistance to dieldrin, which confers limited cross-resistance to fipronil, was detected in 95% of GNV-R strain individuals. Logistic regression analysis showed that A302S mutation frequency correlates with neurological insensitivity as shown by electrophysiology data. Overall, results of synergism bioassays, electrophysiological recordings, and A302S mutation frequency measurements suggest that fipronil resistance in the GNV R strain is caused by the combined effects of enhanced metabolism by cytochrome P450s and target-site insensitivity caused by the A302S-encoding mutation in the resistance to dieldrin gene. PMID- 22308781 TI - Relationships between infection, dissemination, and transmission of West Nile virus RNA in Culex pipiens quinquefasciatus (Diptera: Culicidae). AB - Culex pipiens quinquefasciatus Say fed blood containing 6.8 +/- 0.3 logs (mean +/ SE) plaque-forming units of West Nile virus (WNV)/ml were maintained at 28 degrees C for incubation periods (IP) of 7, 14, or 21 d. Several attributes of vector competence were determined at each IP using quantitative real-time reverse transcriptase polymerase chain reaction to estimate plaque forming unit equivalents including: infection rate (WNV-positive abdomens), dissemination rate (WNV-positive legs or thoraces), combined dissemination rate (WNV-positive legs and thoraces), transmission rate (WNV-positive saliva), and WNV titers in abdomens, legs, thoraces, and saliva. Each rate increased or was equivalent with increasing IP. Mosquitoes transmitting WNV in saliva also had significantly higher IP-dependent WNV titers in abdomens, legs, and thoraces. Titers of WNV in abdomens were significantly correlated with titers in legs and thoraces, but the degree of association changed with IP. However, titers of abdomens, legs, and thoraces were not correlated with WNV presence or titer in the saliva. The results show that WNV presence or titer in the saliva of infected Cx. p. quinquefasciatus was not directly influenced by processes involved in WNV replication in other tissues. The processes controlling midgut infection and escape are, in part, independent from the infection processes in other tissues. The relationship between infection, dissemination, and transmission varied over time. The infection and replication of WNV in different tissues is likely influenced by different barriers encountered during the extrinsic incubation period. The significance of these observations for understanding vector competence is discussed. PMID- 22308782 TI - Evaluating sampling method bias in Culex tarsalis and Culex quinquefasciatus (Diptera: Culicidae) bloodmeal identification studies. AB - Determining the bloodmeal hosts of the Culex vectors of encephalitis viruses such as West Nile virus is essential for understanding the role of these mosquitoes in enzootic and epidemic transmission. Although molecular techniques have increased our knowledge of blood feeding patterns by allowing host identification to the species level, few studies have focused on the role that sampling methods may play in determining these patterns. In the current study, we identified 644 bloodmeals from Culex tarsalis Coquillett and Culex quinquefasciatus Say females collected in CO2 traps (dry ice-baited Center for Disease Control traps), in gravid traps, and aspirated from resting sites. There was no significant difference in the bloodmeal host apportionment in sampling methods such as gravid traps and resting collections that collected fully engorged females. However, CO2 traps that collected partially fed females had a significantly different apportionment of hosts than either gravid or resting collections. Bloodfed females from CO2 traps had either fed on only a small subset of available host species or were biased toward more mammalian and fewer nonpasserine avian feeds than females from other collections. Because both full and partial bloodmeals can contribute to viral transmission, obtaining Culex bloodmeal collections from multiple sampling methods may be important to fully interpret the role of these mosquitoes as maintenance and/or bridge vectors. PMID- 22308783 TI - Enterococcus faecalis OG1RF:pMV158 survives and proliferates in the house fly digestive tract. AB - Enterococcus faecalis is an important nosocomial pathogen and house flies have been implicated in the dissemination of this bacterium. In this study, GFP expressing E. faecalis OG1RF:pMV158 was used to track the fate of the bacterium in the digestive tract of the house fly, Musca domestica (L.) to assess the vector potential of this insect for E. faecalis. Colony forming unit (CFU) counts were obtained from viable fluorescing E. faecalis recovered from mouthparts and digestive tract regions (labelum, foregut, midgut, and hindgut) at 1, 4, 8, 24, 48, 72, and 96 h after the bacterial exposure. Bacterial counts were significantly highest in the midgut at 1h and 4h and declined during the first 24 h. In the labelum, E. faecalis concentrations were low within the first 24 h and then greatly increased. Bacterial counts and direct observations of the digestive tract under a dissecting microscope with ultra violet light revealed that E. faecalis peaked in the crop after 48 h and remained high until the end of the experiment. Concentrations of E. faecalis in the hindgut were low when compared with other parts of the digestive tract. Microscopy and CFU counts suggest that E. faecalis was digested in the midgut but proliferated in the crop. Both drinking water and feed (flaked corn) sampled at the end of the assay (96 h) were contaminated by fluorescing E. faecalis, demonstrating that the flies disseminated E. faecalis. Our data support the notion that house flies can act as a bioenhanced vector for bacteria PMID- 22308784 TI - Prevalence and genotyping of tick-borne encephalitis virus in questing Ixodes ricinus ticks in a new endemic area in western Switzerland. AB - Tick-borne encephalitis virus (TBEV) is the causative agent of tick-borne encephalitis (TBE) and causes neurological disease in humans in Eurasia. TBEV is transmitted by ticks of the genus Ixodes. Currently 10,000-12,000 clinical cases are reported annually in approximately 30 TBE endemic countries. Since 1990 the epidemiology of TBE is characterized by a global increase of clinical cases and an expansion of risk areas. Similar trends are also observed in Switzerland but few studies confirmed the emergence of new TBE foci by detecting viral RNA in field-collected ticks. In this study, free-living Ixodes ricinus (L.) ticks from one nonendemic and three new TBE endemic regions located in the Western part of Switzerland were screened during four consecutive years (2007-2010) for the presence of TBEV. A total of 9,868 I. ricinus ticks (6,665 nymphs and 3,203 adults) were examined in pools for TBEV by real-time reverse transcription polymerase chain reaction. Our results confirmed the presence of viral RNA in 0.1% (6/6120) of questing ticks collected in one new endemic region. Among TBE endemic sites, the minimal infection rate per 100 ticks tested ranged from 0.21 (1/477) to 0.95 (1/105). Four positive samples were sequenced and phylogenetic analysis of the NS5 gene showed that all TBEV nucleotide sequences belonged to the European subtype and were split into two distinct lineages originating probably independently from two distinct foci located North-East and East of the study region. PMID- 22308785 TI - Culex flavivirus and West Nile virus in Culex quinquefasciatus populations in the southeastern United States. AB - Little is known of the interactions between insect-only flaviviruses and other arboviruses in their mosquito hosts, or the potential public health significance of these associations. The specific aims of this study were to describe the geographic distribution, prevalence, and seasonal infection rates of Culex flavivirus (CxFV) and West Nile virus (WNV) in Culex quinquefasciatus Say in the Southeastern United States, investigate the potential association between CxFV and WNV prevalence in Cx. quinquefasciatus and describe the phylogenetic relationship among CxFV and WNV isolates from the Southeastern United States and around the world. Using ArboNET records, 11 locations were selected across Georgia, Mississippi, and Louisiana that represented a range of WNV human case incidence levels. Cx. quinquefasciatus were trapped weekly throughout the summer of 2009 and pools were screened for flavivirus RNA by reverse transcriptase polymerase chain reaction. Cx. quinquefasciatus from Georgia had significantly higher CxFV infection rates than either Mississippi or Louisiana. CxFV was not detected in Mississippi after July, and no CxFV was detected in Cx. quinquefasciatus in Louisiana. In Georgia, CxFV infection rates were variable between and within counties and over time. WNV infection rates were not significantly different across states or months, and WNV sequences from all three states were identical to each other in the envelope and NS5 gene regions. Phylogenetically, NS5 and E gene sequences from Georgia CxFV isolates clustered with CxFV from Japan, Iowa, and Texas. Multiple CxFV genetic variants were found circulating simultaneously in Georgia. No evidence was found supporting an association between WNV and CxFV infection prevalence in Cx. quinquefasciatus. PMID- 22308786 TI - Entomological surveillance for flaviviruses at migratory bird stopover sites in Hokkaido, Japan, and a new insect flavivirus detected in Aedes galloisi (Diptera: Culicidae). AB - To investigate the possible spread of West Nile virus (WNV) into Japan, we carried out entomological surveillance for flaviviruses at migratory bird stopover sites in Hokkaido, Japan, during 2003-2006. A total of 3,826 mosquitoes, identified as 15 species in five genera, were collected and 2,465 of these were grouped into 123 pools that were assayed for cytopathic effects on mosquito and mammalian cell cultures and for flavivirus RNA by reverse transcription polymerase chain reaction using flavivirus universal primer sets for fragments of the NS3 and NS5 genes. Neither WNV nor other mosquito-vertebrate transmitted flaviviruses were detected in mosquitoes collected at any of the sites in Hokkaido, but five Culex flaviviruses and one novel Aedes galloisi flavivirus were identified from Culex pipiens L. s. l. and Aedes galloisi Yamada, respectively. Genetic and phylogenetic analyses based on the partial NS5 nucleotide sequences classified Aedes galloisi flavivirus with the insect flavivirus, but distant from Cell fusing agent, Kamiti river virus, and Culex flaviviruses, showing <74% sequence identities. Polymerase chain reaction-based bloodmeal analysis of 79 females showed that all of the Aedes and Ochlerotatus mosquitoes fed on mammals (deer and humans), whereas, Cx. pipiens s. l. mosquitoes fed on both of avian (ducks and sparrows, 85.7%) and mammalian hosts (dog, 14.3%). We suggest that to date WNV has not become established in Japan. PMID- 22308787 TI - Two species of Microcerella (Diptera: Sarcophagidae) found in highland arid landscapes of Argentina, during forensic studies. AB - Two species of Microcerella Macquart were obtained from pig and llama corpses during a decomposition field experiment in highlands desert landscapes of Catamarca, Argentina. We sampled four pig and two llama carcasses. Microcerella antofagastensis sp. nov. is described, and M. quimaliensis (Lopes, 1982) is redescribed. Illustrations of male and female terminalia of both species are provided and should allow a correct identification. Notes on the biology of both species are given. PMID- 22308788 TI - Genome sizes of forensically relevant Diptera. AB - Genome size estimates for both sexes of forensically relevant Diptera from 17 species (four families) are reported herein. Average genome sizes ranged from 425.8 Mb for female Chrysomya rufifacies to 1,197.4 Mb for male Haematobia irritans. These estimates are useful not only for molecular studies, but also for determination of the species and sex of immatures. Species in three of the sampled families had sexually dimorphic genome sizes, presenting a new tool useful for the determination of sex in these species, especially in the immature stages where sexes are morphologically difficult or impossible to identify. In addition, closely related species had significantly different genome sizes, suggesting the use of flow cytometry as a new tool for species identification of some species of forensically relevant larvae. PMID- 22308789 TI - Economic impact of stable flies (Diptera: Muscidae) on dairy and beef cattle production. AB - Stable flies, Stomoxys calcitrans (L.), are among the most damaging arthropod pests of cattle worldwide. The last estimate of their economic impact on United States cattle production was published 20 yr ago and placed losses at $608 million. Subsequently, several studies of effects of stable flies on beef cattle weight gain and feed efficiency have been published, and stable flies have become increasingly recognized as pests of cattle on pasture and range. We analyzed published studies and developed yield-loss functions to relate stable fly infestation levels to cattle productivity, and then estimated the economic impact of stable flies on cattle production in the United States. Four industry sectors were considered: dairy, cow-calf, pastured stockers, and feeder cattle. In studies reporting stable fly infestation levels of individual herds, median annual per animal production losses were estimated to be 139 kg of milk for dairy cows, and 6, 26, and 9 kg body weight for preweanling calves, pastured stockers, and feeder cattle, respectively. The 200,000 stable flies emerging from an average sized winter hay feeding site reduce annual milk production of 50 dairy cows by an estimated 890 kg and weight gain of 50 preweanling calves, stockers, or feeder cattle by 58, 680, or 84 kg. In 2009 dollars, the value of these losses would be $254, $132, $1,279, or $154, respectively. Using cattle inventories and average prices for 2005-2009, and median monthly infestation levels, national losses are estimated to be $360 million for dairy cattle, $358 million for cow calf herds, $1,268 million for pastured cattle, and $226 million for cattle on feed, for a total impact to U.S. cattle industries of $2,211 million per year. Excluded from these estimates are effects of stable flies on feed conversion efficiency, animal breeding success, and effects of infested cattle on pasture and water quality. Additional research on the effects of stable flies on high production dairy cows and nursing beef calves is needed to increase the reliability of the estimates. PMID- 22308790 TI - Evaluation and modification of off-host flea collection techniques used in northwest Uganda: laboratory and field studies. AB - Quantifying the abundance of host-seeking fleas is critical for assessing risk of human exposure to flea-borne disease agents, including Yersinia pestis, the etiological agent of plague. Yet, reliable measures of the efficacy of existing host-seeking flea collection methods are lacking. In this study, we compare the efficacy of passive and active methods for the collection of host-seeking fleas in both the laboratory and human habitations in a plague-endemic region of northwest Uganda. In the laboratory, lighted "Kilonzo" flea traps modified with either blinking lights, the creation of shadows or the generation of carbon dioxide were less efficient at collecting Xenopsylla cheopis Rothchild and Ctenocephalides felis Bouche fleas than an active collection method using white cotton socks or cotton flannel. Passive collection using Kilonzo light traps in the laboratory collected significantly more X. cheopis than C. felis and active collection, using white socks and flannel, collected significantly more C. felis than X. cheopis. In field studies conducted in Uganda, Kilonzo traps using a flashlight were similar in their collection efficacy to Kilonzo traps using kerosene lamps. However, in contrast to laboratory studies, Kilonzo flea traps using flashlights collected a greater number of fleas than swabbing. Within human habitations in Uganda, Kilonzo traps were especially useful for collecting C. felis, the dominant species found in human habitations in this area. PMID- 22308791 TI - Rehydration driven RNAi: a novel approach for effectively delivering dsRNA to mosquito larvae. AB - The soft bodies and aquatic habitats of mosquito larvae pose a challenge for applying standard RNA-interference techniques to silence expression of target genes. Here we describe a novel technique for delivering double-stranded RNA into mosquito larvae by exploiting the larva's dehydration tolerance. Larvae were dehydrated in a NaCl solution and then rehydrated in water containing double stranded RNA. Using larvae of Culex pipiens (L.) we demonstrated the principle by knocking down expression of the gene encoding heat shock protein 90. The knockdown persisted through the pupal stage and into adulthood, with a knockdown of approximately 77% still evident on the third day of adult life. We anticipate that this relatively simple procedure will prove useful for knocking down expression of other genes as well, in larvae of this mosquito and in others. PMID- 22308792 TI - A third Amblyomma species and the first tick-borne rickettsia in Chile. AB - During November 2010, three ticks were collected from three dogs living in the rural area of Arica, northern Chile. Morphological analyses of the ticks in the laboratory revealed that they were most similar to Amblyomma maculatum Koch and Amblyomma triste Koch. However, because of unique metatarsal spurs, neither of the Chilean specimens could be assigned with certainty to A. maculatum or A. triste, based on external morphology. The mitochondrial 16S rRNA gene partial sequences obtained from two Chilean specimens were 99.5% identical to A. triste from Uruguay, and 99.0% identical to A. maculatum from the United States. Through phylogenetic analysis inferred from partial 16S rRNA sequences, the Chilean specimens were classified as A. triste. Molecular analyses also showed that one of the three Chilean ticks was infected by Candidatus 'Rickettsia andeanae'. These findings extend the geographical distribution of A. triste to Chile, where no tick-associated rickettsia had been reported previously. PMID- 22308793 TI - Spatial and temporal abundance of three sylvatic yellow fever vectors in the influence area of the Manso hydroelectric power plant, Mato Grosso, Brazil. AB - Human biting catches of sylvatic yellow fever (SYF) vectors were conducted at eight stations in the influence area of the Manso hydroelectric power plant (Central Brazil) in sampling campaigns every 2 mo from July 2000 to November 2001. In total, 206 individuals were captured and classified as one of three species important for the transmission of SYF in Mato Grosso state: Haemagogus (Haemagogus) janthinomys (Dyar, 1921); Haemagogus (Conopostegus) leucocelaenus (Dyar & Shannon, 1924); and Sabethes (Sabethoides) chloropterus (Humboldt, 1819). The highest vector abundance was observed during the rainy season (November through March) and SYF vectors were present in all sampling points throughout the year, mainly in riparian and shadowed transitional forests at shadowed ramps. PMID- 22308794 TI - Laboratory evaluation of rubidium as a long-lasting marker for bloodfeeding sand flies (Diptera: Psychodidae). AB - The objective of this study was to evaluate the use of the trace element rubidium (Rb) as a long-lasting systemic biomarker for bloodfeeding females of the sand fly Phlebotomus papatasi Scopoli. Baits containing Rb chloride were found to be palatable to hamsters in this study. We were able to detect Rb using a portable X ray fluorescence analyzer in all sand flies that fed on Rb-treated hamsters for at least 14 d postbloodmeal. We also detected Rb in sand flies that took a bloodmeal from hamsters up to 10 d after the hamsters were withdrawn from a Rb treated diet. Results of this study constitute proof of concept for the incorporation of Rb chloride into rodent baits for marking bloodfeeding sand flies, and suggest that Rb marking could be used as a technique for evaluating rodent-targeted sand fly control methods and in ecological studies on sand flies. PMID- 22308795 TI - Louse flies (Diptera: Hippoboscidae: Ornithomyinae) of the Republic of Korea: an updated checklist, including two new records of bird louse flies. AB - One genus, Ornithoica Rondani, and two species, Ornithoica momiyamai Kishida, and O. unicolor Speiser, are reported for the first time from the Republic of Korea. A total of six species, including two new records, of louse flies were collected from 78 birds belonging to 35 species from Seoul and Incheon Metropolitan Areas and Gyeonggi, Gangwon, Gyeongsangbuk, Jeollabuk, and Jeollanam Provinces, 2005 2010. An updated checklist of Korean hippoboscids consisting of seven genera (Hippobosca L., Icosta Speiser, Lipoptena Nitzsch, Ornithoica Rondani, Ornithoctona Speiser, Ornithomya Lattreille, and Ornithophila Rondani) and 11 species is presented, including hosts, collection records, and repositories. PMID- 22308796 TI - [The minimum efficiency of drugs against Alzheimer's disease]. PMID- 22308797 TI - [Henoch-Schonlein purpura in the elderly]. PMID- 22308798 TI - [Ovarian reserve]. AB - Ovarian reserve assessment has become critical when counselling infertile couples. This evaluation should be conducted in all women over 35 years, or earlier in case of familial history of premature ovarian failure, gonadotoxic treatment of short menstrual cycles. The first step for ovarian reserve assessment is to measure basal hormonal status, i.e. day 3 FSH and estradiol. If necessary, antral follicle count performed by a skilled operator and/or serum AMH level can give some relevant additional information. The historical concept of 2 years waiting does not make sense any more regarding the current delay in childbearing. Therefore, the infertility workup, and particularly ovarian reserve assessment, should be initiated after 6 months of infertility in all women over 35 years of age. PMID- 22308799 TI - [Primary mesenteric volvulus]. PMID- 22308800 TI - [Alarm and detection signs of upper digestive and respiratory tract cancers]. AB - Upper digestive and respiratory tract cancers represent, in frequency, the fourth cancer in the general population. They are responsible of non-specific symptoms. Clinical examination of this anatomical region is difficult for a layman for whom the specific material is not available to diagnose a small tumour The objective of this paper was to make more sensitive the general practictioners about these type of cancers. PMID- 22308801 TI - [Prevent venous thromboembolism]. PMID- 22308802 TI - [Prevention of venous thromboembolism in medical patients]. AB - Thromboembolism, which frequently associates deep venous thrombosis and pulmonary embolism, is a serious and potentially fatal condition that often complicates the outcome of patients hospitalized in the medical area. This disease is multifactorial and chronic, due to the risks of recurrence, and can cause severe complications (death, pulmonary hypertension, residual postphlebitic syndrome). Randomized, controlled clinical trials (Medenox, Prevent, Artemis) demonstrated the unquestionable preventive benefits of low-molecular-weight heparins and fondaparinux from hospitalization on, in a specific group of "medical" patients at minimum risk of bleeding. These findings support the systematic use of medical thromboprophylaxis in patients meeting the study criteria, as per the ACCP 2008 guidelines. However, only 50% of the patients in which thromboprophylaxis is indicated receive a treatment. This under-use can be explained by with the wide variety of patients, as well as the difficulty to assess thromboembolic risks. Overall risk assessment models, simple and clinically relevant, were developed to facilitate the decision to initiate an appropriate thromboprophylaxis in patients hospitalized in medical area. PMID- 22308803 TI - [Prevention of venous thromboembolism in surgical patients]. AB - Venous thromboembolism is a major risk for surgical patients during the perioperative period. Prevention of perioperative venous thromboembolism remains a critical component of surgical patient care. The risk for venous thromboembolism in surgical patients can be stratified by their risk factors and by the type of operation. Pharmacological prophylaxis for venous thromboembolism includes unfractionated heparin, low-molecular weight heparin, fondaparinux, vitamin K antagonists, and the new oral anticoagulants (direct factor Xa inhibitors or direct thrombin inhibitor). Mechanical devices such as graduated compression stockings, intermittent pneumatic compressions, and venous foot pumps are also effective modalities for venous thromboembolism prophylaxis. The optimal preventive measure of venous thromboembolism should be based on the degree of risk for venous thromboembolism while balancing potential treatment benefits and risks in each individual patient. PMID- 22308804 TI - [Guidelines about venous thromboembolism]. AB - Prevention of venous thromboembolism relies on compliance to guidelines. Different guidelines and recommendations regarding medical and surgical situations are available from international and national sources. New strategies for venous thromboembolism prevention have been recently developed. Thus, guidelines must be constantly revisited in this field. Guidelines for prevention of venous thromboembolism in surgery, issued by the French Society of Anaesthesia and Intensive Care in 2005 are still valid. New recommendations for hip and knee arthroplasty regarding the indication for new oral anticoagulants have been issued. In bariatric surgery, prevention strategies have been clarified. In plastic and aesthestic surgery, new guidelines are now available. More precise recommendations and suggestions have been proposed for fragile patients (elderly, low body weight, altered renal function) who are at higher risk for haemorrhagic and also thrombotic events after surgery. PMID- 22308805 TI - [Mechanical prophylaxis of venous thromboembolism]. AB - Mechanical devices for the prevention of venous thromboembolism (VTE) act on venous stasis and include static systems: the graduated compression stockings (or elastic stockings or anti-embolism stockings) and dynamical systems: intermittent pneumatic compression and venous foot pump. The main advantage of these devices is that they have no risk of bleeding. If the prevention of VTE is based primarily on drug prophylaxis, mechanical devices are recommended primarily for patients with high risk of bleeding, if there is contraindication to anticoagulants. Alone or in combination with drug prophylaxis, their efficacy on deep vein thrombosis prevention is well documented in surgery, but the evidence is insufficient for the prevention of pulmonary embolism and in other settings. Their interest in stroke is called into question after the results of the CLOTS 1 and 2 studies. These results, beyond the context of stroke, have raised numerous questions about the real benefit/risk ratio of mechanical devices for the prevention of VTE. They highlight the need to assess or re-evaluate mechanical devices by rigorous clinical trials. PMID- 22308806 TI - [Thromboembolic events and air travel]. PMID- 22308807 TI - [New anticoagulants]. AB - The range of anticoagulants has been very active recently with the development of new compounds including injectable anti-Xa such as fondaparinux, and new oral drugs which can be divided into anti-IIa with dabigatran, and anti-Xa, such as rivaroxaban and apixaban still in the development stage. Others are coming forward. They are more convenient to use and do not require routine coagulation monitoring. However, several points need to be clarified and the place for each drug remains to be determined. In case of massive bleeding, management is unclear and none of these newer agents has a specific antidote that completely reverses its anticoagulant effect. PMID- 22308808 TI - [Epidemiologic and therapeutic advances in superficial venous thrombosis of the legs]. AB - Thromboses affecting venous superficial system have been considered as benign diseases. Recent studies demonstrate that they might be associated with more severe venous events (as deep venous thrombosis [DVT] or pulmonary embolism [PE]), initially or during 3-month followup. The POST study presents clinical evolution of 844 patients with superficial venous thrombosis (SVT) of lower limbs. Of note, concomitant DVT and/or symptomatic PE were initially found in one quarter of them. Among the 586 patients with isolated SVT (i. e. without DVT or symptomatic PE, and at more than 3 cm of the saphenofemoral junction), 10% presented with DVT, PE, recurrent or extensive SVT during the 3-month follow-up. These results, as the heterogeneous therapeutic management, were confirmed by another cohort study (OPTIMEV). In the CALISTO study, Fondaparinux, at a dose of 2.5 mg once a day for 45 days was effective in the treatment of patients with isolated SVT of the legs and did not have serious side effects. In absence of contra-indication, this treatment may be preferred in patients with confirmed isolated SVT of lower limb. PMID- 22308809 TI - [Secondary prevention of venous thromboembolism in patients with cancer]. AB - Venous thromboembolism occurs in about 10% of patients with cancer. In this setting, vitamin K antagonists have been associated with a high risk of recurrent disease and major bleeding. Low-molecular-weight heparin allows reducing by 50% the rate of recurrent venous thromboembolism as compared to vitamin K antagonists. Even with low-molecular-weight heparin, recurrent venous thromboembolism occurs in up to 6% of the patients. In this case it has been suggested to increase the dosage of low-molecular-weight heparin. Vena cava filtration probably plays a minor role in setting. After the sixth month, prolongation of low-molecular-weight-heparin or switch to vitamin K antagonist should be discussed on a case by case basis. PMID- 22308811 TI - [Events indicative of a more serious systemic lupus immediately]. PMID- 22308810 TI - [When to think about lupus?]. AB - Clinical and biological manifestations of systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease, which is characterized by the presence of autoantibodies directed against various nuclear antigens. It is typically a relapsing and remitting multi-system disease, and patients can present in many different ways. The most common manifestations include rash, arthritis and fatigue. At the other end of the spectrum, SLE can cause nephritis, various neurological manifestations, and severe cytopenia. Physicians should be aware of the vast clinical spectrum of the disease as well as of its characteristic biological features. PMID- 22308812 TI - [Diagnosis criteria, classification and disease activity assessment in systemic lupus erythematosus]. PMID- 22308813 TI - [Antiphospholipid syndrome]. PMID- 22308814 TI - [Treatment of systemic lupus erythematosus]. AB - Systemic lupus erythematosus is a chronic autoimmune disease. Treatment goals are to cure flares and to prevent them as well as long-term complications and drugs toxicity. Effort to improve patient knowledge and education should be a priority. SLE treatments range from long term prescription of antimalarial agents, to corticosteroids and, in severe cases, immunosuppressive agents. Patients should receive advice on environmental triggers and photoprotective measures. Other key points of the treatment include early prevention of atherosclerosis and infectious diseases. Physician must be readily available for the patient to detect flares, infections, cardiovascular events, drugs side-effects and psychiatric events. Birth control and pregnancy should be discussed early with the patient. PMID- 22308815 TI - [Information, patient education and compliance in systemic lupus erythematosus]. PMID- 22308816 TI - [Contraception, fertility, pregnancy and menopause in women with systemic lupus erythematosus]. PMID- 22308817 TI - [Drug-induced lupus erythematosus]. PMID- 22308818 TI - [From guidelines to centers of evidence]. PMID- 22308819 TI - [Importance of new examinations in the management of visual impairment]. PMID- 22308820 TI - [Legislation for persons with chronic progressive disabling diseases]. PMID- 22308822 TI - [Andropause]. PMID- 22308821 TI - [Chronic diarrhea: which diagnostic approach?]. PMID- 22308823 TI - [Chronic respiratory failure]. PMID- 22308824 TI - [Parkinson's disease]. PMID- 22308825 TI - [Acute respiratory distress in the adult]. PMID- 22308826 TI - [Acute fever in an immunocompromised patient]. PMID- 22308827 TI - [How the Supreme Court has changed the patients' information]. PMID- 22308828 TI - Home dialyzors show what's possible. PMID- 22308829 TI - The role of race in survival among patients undergoing dialysis. PMID- 22308830 TI - Medicare Part D: challenges for dialysis patients (part 2 of 2): opportunities to improve patient experiences. PMID- 22308831 TI - Meaningful use: where do we go from here? PMID- 22308832 TI - New AAMI standards for dialysis fluids. PMID- 22308833 TI - Intracranial cysts: large-scale information is needed. PMID- 22308834 TI - The endocrine spectrum of intracranial cysts in childhood and review of the literature. AB - Intracranial cysts (ICC) may cause a wide spectrum of endocrinological disorders. We evaluated 27 patients who were diagnosed with ICC during investigation for neuroendocrine dysfunctions and reviewed the relevant literature. The types of ICC in the patients were arachnoid cysts (n = 13); Rathke cleft cysts (n = 7); pineal cysts (n = 5); an ependymal cyst (n = 1) and a cavum septum pellucidum cyst (n = 1). The neuroendocrine dysfunctions of the patients were obesity (n = 7), isolated growth hormone deficiency (n = 6), central precocious puberty (n = 6), multiple pituitary hormone deficiency (n = 3), central diabetes insipidus (n = 1), growth hormone deficiency and central precocious puberty (n = 1), obesity and galactorrhea (n = 1), obesity and hypogonadotropic hypogonadism (n = 1) and growth hormone neurosecretory dysfunction (n = 1). Only three patients, who had arachnoid cysts, showed neurologic symptomatology. Although three patients underwent surgery, no improvements in endocrinological dysfunctions were observed. ICC should be considered when evaluating patients with endocrinological problems and patients with coincidental ICC should be recommended for follow-up. PMID- 22308835 TI - Radioiodine treatment in pediatric Graves' disease and thyroid carcinoma. AB - Graves' disease (GD) is the most common cause of hyperthyroidism in pediatric patients. Most pediatric thyroid cancer is differentiated thyroid cancer (DTC). The two diseases can be treated using different methods, such as antithyroid drug, radioactive iodine (RAI), and surgery for GD and surgery and RAI for DTC. RAI can be used to treat pediatric GD and DTC. In the article, we reviewed the RAI application in pediatric GD and DTC. PMID- 22308836 TI - Perineal ectopic testis: a rare cause of empty scrotum. PMID- 22308837 TI - Normal thyroid function in young adults who were born very preterm. AB - There is some evidence for elevated thyrotropin (TSH) levels in children born preterm, but follow-up studies into adulthood are lacking. We tested whether thyroid function in young adults born at a gestational age < 32 weeks, with either an appropriate (appropriate for gestational age, AGA) or low birth weight for gestational age (small for gestational age, SGA), differed from that in age matched controls. We made our measurements when the study participants reached 21 years of age. Serum concentrations of TSH and free T4 (fT4) and body composition were measured in subjects born preterm and AGA (n = 29) or SGA (n = 28), and in non-preterm controls (n = 30). The TSH and fT4 concentrations of participants were within normal limits. Free T4 levels in subjects born preterm were slightly higher than those in controls: 17.0 +/- 2.4 (AGA) and 17.2 +/- 1.7 (SGA) vs. 16.1 +/- 1.9 pmo/L (p = 0.04). TSH concentrations did not differ between groups. From these preliminary data, we conclude that young adults born preterm have a normal thyroid function. PMID- 22308838 TI - Does clinical management impact height potential in children with severe acquired hypothyroidism? AB - BACKGROUND: Severe acquired hypothyroidism often results in significant height deficit due to rapid bone age advancement following treatment. Whether gradual correction of hypothyroidism and/or adjunctive growth-promoting therapies (GPTs) augment final adult height (FAH) is controversial. OBJECTIVE: To investigate time to euthyroidism, pace of bone age advancement (deltaBA/deltaCA), and impact of GPTs on FAH. METHODS AND PATIENTS: Retrospective review of 21 children (10.1 +/- 3.0 years) with profound hypothyroidism. RESULTS: Baseline bone age standard deviation score (SDS) was -4.1 +/- 1.8, whereas height SDS was -3.0 +/- 1.1. Average time to euthyroidism was 9.7 months (2.3-33.7 months). Average deltaBA/deltaCA was 2.3 +/- 0.9. Six of 13 patients at FAH received GPTs. No correlation was found between time to euthyroidism and rate of skeletal maturation. No difference in height outcome was seen between those who received GPTs and those who did not. CONCLUSIONS: Neither time to euthyroidism nor use of GPTs significantly affected height potential in our patients. PMID- 22308839 TI - Neurodevelopment of preterm infants born at 28 to 36 weeks of gestational age: the role of hypothyroxinemia and long-term outcome at 4 years. AB - CONTEXT: Hypothyroxinemia in premature neonates may affect long-term neurodevelopment. OBJECTIVE: This study aimed to examine the effects of hypothyroxinemia of the newborn preterm infants born at 28-36 weeks of gestational age (GA) on the neurodevelopment at 4 years of age. PATIENTS: Prospective observational cohort study conducted in Madrid, Spain. Forty-six preterm infants were included in the study. MAIN OUTCOME: The effects of the exposure to neonatal hypothyroxinemia on mental development were examined. RESULTS: Using regression analyses we found that neonatal T4 had a positive association with general cognitive index and Verbal index, and neonatal FT4 with general cognitive and Memory indexes at 4 years of age. CONCLUSIONS: The exposure to hypothyroxinemia during the neonatal period of late preterm infants may play role in neurodevelopmental delays. Higher T4 level means a trend to higher indexes and low T4 level means a lower neurodevelopmental indexes at 4 years of age. PMID- 22308840 TI - Central hypothyroidism following chemotherapy for acute lymphoblastic leukemia. AB - BACKGROUND: It has been suggested that chemotherapy per se might impair the hypothalamus-pituitary-thyroid axis of childhood cancer survivors. OBJECTIVE: We examined six patients treated for acute lymphoblastic leukemia (ALL) with chemotherapy alone, with suspicious central hypothyroidism (CH). SUBJECTS AND METHODS: ALL was diagnosed at a mean age of 3.8 years (range 0.3-6 years), the mean follow-up is 6 years (range 6-13 years). Auxological data were recorded, and thyroid function, autoimmunity and ultrasonography (US) were evaluated. Three individuals underwent a thyrotropin-releasing hormone (TRH) test and a magnetic resonance imaging (MRI) scan of the hypothalamic-pituitary region. RESULTS: All study participants showed negative thyroid autoimmunity, normal thyroid ultrasound, and thyroid-stimulating hormone (TSH) above the normal range; free T4 (fT4) was abnormally low in two patients. After TRH infusion all patients showed TSH increase and slow TSH decline. CONCLUSIONS: Our study shows that CH could arise at any time after childhood leukemia following only chemotherapy treatment. Although overt hypothyroidism was detected in only two patients, a careful follow up of thyroid function is also recommended for ALL survivors not treated by irradiation. PMID- 22308841 TI - The prevalence of non-alcoholic fatty liver disease and metabolic syndrome in obese children. AB - BACKGROUND AND AIM: In the context of present epidemic of childhood obesity, we aimed to find the prevalence of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) in a cohort of obese children. METHODOLOGY: Retrospective chart analysis of 700 obese children was done for their anthropometric and biochemical investigations. RESULTS: Some 15.4% (9.8% girls, 22% boys) subjects had NAFLD (ALT > 40 IU/L) after excluding other identifiable causes of liver dysfunction. Age, weight, TG, fasting serum insulin and HOMA-IR levels were higher in children with NAFLD. Twenty-eight percent children had MS. Children with NAFLD had an odds ratio of 2.65 for having MS (boys 4.6, girls 1.7). The prevalence of MS increased with age 5-9 years (21%), 10-16 years (30%), 17-20 years (35%). CONCLUSION: Given high prevalence of NAFLD and MS in obese children, childhood obesity should be seriously considered as a disease and not just a cosmetic issue. PMID- 22308842 TI - Retinol binding protein 4 is associated with adiposity-related co-morbidity risk factors in children. AB - OBJECTIVE: In adults, elevated levels of retinol binding protein 4 (RBP4) have been associated with biochemical markers of adiposity-related co-morbidities including insulin resistance, dyslipidemia, hypertension, and abdominal obesity. This study examined the relationship between RBP4 and risk factors for co morbidities of adiposity in a population of ethnically diverse children in early- to mid-adolescence in the public school system of New York City. MATERIALS/METHODS: We analyzed anthropometric (body mass index, % body fat, waist circumference), metabolic (lipids, glucose), and inflammatory (TNF-alpha, interleukin-6, C-reactive protein, adiponectin) markers for adiposity-related co morbidities and serum alanine aminotransferase (ALT) in 106 school children (65 males, 41 females) 11-15 years of age (mean +/- SD = 13.0 +/- 0.1 years) who were enrolled in the Reduce Obesity and Diabetes (ROAD) project. Insulin sensitivity was assessed by quantitative insulin sensitivity check index. Insulin secretory capacity was measured as acute insulin response and glucose disposal index. RESULTS: Serum RBP4 was significantly correlated directly with ALT, triglycerides, and triglyceride z-score, and inversely correlated with adiponectin. Correlations with ALT and adiponectin remained significant when corrected for % body fat, age, and gender. There were significant ethnic differences in the relationship of RBP4 to ALT, glucose disposal index and adiponectin. CONCLUSIONS: In early- to mid-adolescents, circulating concentrations of RBP4 are correlated with multiple risk factors for adiposity related co-morbidities. The observation that many associations persisted when corrected for % body fat, suggests that RBP4 can be viewed as an independent marker of adiposity-related co-morbidity risk in children. PMID- 22308843 TI - Circulating adipocyte fatty acid-binding protein, juvenile obesity, and metabolic syndrome. AB - Adipocyte fatty acid-binding protein (A-FABP) links obesity and metabolic syndrome (MetS) and might be targeted in future therapies. Its utility as a MetS biomarker has been suggested in adults but has not been examined in children/adolescents. Our objectives were to identify metabolic parameters associated with A-FABP elevation in children and adolescents and to evaluate the effect of obesity intervention and A-FABP diagnostic utility. A-FABP and anthropometric, metabolic, and inflammatory indices were measured in 31 lean and 114 overweight/obese children and adolescents and reassessed after obesity intervention (1 year; diet and enhanced physical activity, with or without metformin). A-FABP was significantly higher in overweight/ obese than lean individuals, where it correlated with insulin, waist circumference (WC), and 2-h glucose independent of body mass index (BMI), age, gender, and developmental stage. The pattern of A-FABP associations differed between sexes. As a MetS indicator, A-FABP had 68% accuracy. The weight reduction program was effective in reducing A-FABP, BMI%, WC, triglycerides, and cholesterol. In conclusion, elevation in A-FABP is associated with MetS components independent of BMI status and can be reduced by diet and enhanced physical activity. A-FABP as a single MetS biomarker has a moderate accuracy. PMID- 22308844 TI - Obesity and associated cardiovascular risk factors among schoolchildren in Greece: a cross-sectional study and review of the literature. AB - OBJECTIVE: To examine the prevalence and determinants of obesity and associated cardiovascular risk factors in a sample of Greek children. METHODS: This is a cross-sectional, school-based study of 780 students (9.2 +/- 1.8 years old, 415 boys) conducted in Eastern Attica, the greater area of the city of Athens. The study protocol included anthropometric, blood pressure (BP), and biochemical measurements, as well as dietary and lifestyle habits assessment. A review of Greek studies on childhood obesity was also performed. RESULTS: Approximately 22% of the participants were overweight and 8% were obese, which is in accordance with the results of 24 previous Greek studies showing the childhood overweight/obesity prevalence in the range of 30%. Overweight/obese children compared with normal-weight children had higher BP, lower high-density lipoprotein cholesterol (HDL-C), and higher triglycerides (p < 0.05 for all). Parental weight, consumption of sweets and fast-food, and decreased physical activity were independent determinants of being overweight/obese. Furthermore, overweight/obesity predicted the presence of high BP, low HDL-C, and high triglycerides. CONCLUSION: A close association was revealed between obesity and metabolic abnormalities, underlining the need for early screening and intervention in overweight children in order to address the emerging childhood obesity epidemic in Greece. PMID- 22308845 TI - Peptides from adipose tissue in monitoring energy balance in infants. AB - BACKGROUND/AIM: Overnutrition as well as undernutrition is a serious problem in hospitalized patients, especially in infants. Routine laboratory tests detecting disturbances in energy balance are not specific or accurate. The aim of this study was to evaluate adiponectin and leptin as markers of short-time energy malnutrition. METHODS: Forty-five infants fed orally and parenterally were included in the study. Plasma glucose, leptin and adiponectin were measured in a fasting state and postprandially (1 h after the meal), after a minimum of 24 h of total parenteral nutrition (TPN) and after a minimum of 8 h of intravenous infusion of glucose and crystalloids. RESULTS: Postprandial glucose levels in children fed orally was similar to that observed in children who received intravenous infusion of glucose. The TPN children had slightly higher glucose concentration in contrast to leptin levels which were significantly lower in this group (1.08 mg/mL +/- 0.43) as compared to the others (p < 0.05 in both cases). The mean postprandial levels of the adiponectin in orally fed children were significantly higher (10.7 microg/mL +/- 2.4) than in children with TPN (5.8 microg/mL +/- 2.4; p < 0.001) and in children hydrated intravenously (3.3 microg/mL +/- 2.3; p < 0.001). The concentration of adiponectin correlated significantly with calorie intake. CONCLUSIONS: Oral meal does not affect the plasma concentrations of leptin and adiponectin in infants. Adiponectin is a good short-time marker of energy malnutrition in infants. PMID- 22308846 TI - Effectiveness of pentoxifylline on the cross-sectional area of intima media thickness and functions of the common carotid artery in adolescents with type 1 diabetes. AB - OBJECTIVE: The aim of the present study was to evaluate the effect of oral pentoxifylline on the cross-sectional area of intima media thickness (CSA-IMT) and functions of the common carotid artery, a marker of early atherosclerosis, in adolescents with type 1 diabetes. PATIENTS AND METHODS: Non-invasive ultrasonographic measurements were made in 56 type 1 diabetic patients. The diabetic patients were matched first in terms of age, diabetes duration, major cardiovascular risk factors, including anthropometric and metabolic parameters as well as ultrasonographic measurements, then one individual within each pair randomized into a pentoxifylline group and a placebo (control) group (i.e., 32 on pentoxifylline group and 24 on placebo). Pentoxifylline was administered for 6 months. We investigated the change of CSA-IMT, compliance, distensibility, diastolic wall stress (DWS), and incremental elastic modulus of the common carotid artery at 6 months after pentoxifylline. RESULTS: In comparison of changes in common carotid artery measurements between the two groups, the pentoxifylline treatment group had significantly higher values than the controls for CSA-IMT (-2.6 +/- 0.1 vs. 0.7 +/- 0.4 mm2, p = 0.001) and for DWS (-0.38 +/- 0.02 vs. -0.05 +/- 0.05 mm Hg x 10(2), p < 0.001). In a multivariate regression model for all patients, being in pentoxifylline group was the best predictor of the change DWS (beta = -0.52, p < 0.001). CONCLUSION: Our preliminary results suggest that pentoxifylline has an antiatherogenic action and might modulate risk factors for atherosclerosis in type 1 diabetes. PMID- 22308847 TI - Common adipokine features of neonates and centenarians. AB - Adipose tissue seems to be a pivotal organ in the aging process. We investigated whether healthy aging could have its roots in a sound metabolic condition from the first year of life by evaluating leptin and adiponectin levels in neonates [33 adequate for gestational age (AGA) and 29 small for gestational age (SGA)], 48 centenarians, and 50 healthy elderly subjects. At birth, SGA neonates showed lower leptin levels (SGA 0.88 +/- 0.28; AGA 2.22 +/- 0.91 ng/mL; p < 0.05) and comparable adiponectin levels with respect to AGA. At 1 year, SGA showed increased leptin (SGA 1.74 +/- 0.28; AGA 1.31 +/- 0.19 ng/mL) and slightly reduced adiponectin concentrations (SGA 35.51 +/- 2.53; AGA 38.56 +/- 3.18 microg/mL) than AGA. Centenarians showed lower leptin (centenarians 18.71 +/- 3.78; elderly 34.81 +/- 7.27 ng/mL; p < 0.05) and higher adiponectin levels (centenarians 55.63 +/- 7.7; elderly 33.51 +/- 4.1 microg/mL; p < 0.05) than elderly subjects. Centenarians, like AGA infants during the first year of life, show a favorable adipokine profile, suggesting that the metabolic condition at early age could affect the longevity of an individual. PMID- 22308848 TI - Congenital adrenal hyperplasia: as viewed by parents of affected children in India--a pilot study. AB - A spectrum of myths and misconceptions about congenital adrenal hyperplasia (CAH) is prevalent among the parents of affected children in India. The perceptions of parents may affect several aspects of these children's management, and to explore these perceptions we carried out a cross-sectional questionnaire-based descriptive study during May 2010. Twenty-eight individuals (17 males and 11 females), parents of 22 affected children aged < 5 years, completed the questionnaire. Their responses showed the prevalence among the parents of misconceptions about CAH. These misconceptions were resulting in potentially harmful practices, and in addition there was immense societal pressure on the families as a result of ignorance and myths about the disorder. There is a need for regular CAH education and interaction programs to provide an acceptable platform for the parents and patients, where their concerns can be expressed and shared and their requirements addressed appropriately by a multidisciplinary team. PMID- 22308849 TI - Characteristics and prevalence of non-classical congenital adrenal hyperplasia with a V2811 mutation in patients with premature pubarche. AB - We aimed to determine the prevalence and clinical characteristics of non classical congenital adrenal hyperplasia (NCCAH) with V281L mutation in patients with premature pubarche. An adrenocorticotrophic hormone (ACTH) stimulation test was performed in 14 of the 159 patients with premature pubarche (PP). Patients whose stimulated 17alpha-hydroxyprogesterone (17-OHP) level on the ACTH test was > or =10 ng/mL underwent a mutational analysis of the CYP21 gene. NCCAH was defined in nine (5.7%) patients, all of whom had the V281L mutation. Four of the NCCAH patients were homozygote and four of them were heterozygote. One other patient was compound heterozygote for V281L mutation and the I2 splice mutation. One of the patients with V281L heterozygous mutation developed true precocious puberty and the other one had rapid progressive early puberty and developed polycystic ovary syndrome. ACTH stimulated 17-OHP > or = 10 ng/mL in PP patients is load star to mutation analysis and heterozygote patients should be followed for clinical and biological hyperandrogenism up to completion of the whole 'genome sequence'. PMID- 22308850 TI - Contribution of bone turnover markers to bone mass in pubertal boys and girls. AB - BACKGROUND AND AIMS: The association between bone turnover markers and bone mass in adolescence is not clear. We aimed to evaluate the associations between bone turnover markers and bone mineral content (BMC), density (BMD) and area (BMA). SUBJECTS: A total of 56 adolescents (25 boys, 12.5-17.5 years) participated in the study. METHODS: Bone mass and physical activity (PA) were measured using dual energy X-ray absorptiometry and accelerometers. Osteocalcin and amino-terminal propeptide of type I procollagen (PINP), as markers of bone formation, and beta isomer of the C-terminal telopeptide of type I collagen, as marker of bone resorption were also measured. Sexual maturation, weight, height and average PA were considered as confounders. RESULTS: Positive correlations (Pearson) were observed among the three bone turnover markers (r = 0.7-0.9). Stepwise multiple linear regression analyses showed that PINP was strong and negatively associated with BMC, BMD and BMA in girls, explaining 24.9% of the variance in BMC, 25.6% in BMD and 16.3% in BMA. CONCLUSION: PINP is a strong predictor of bone related variables in pubertal girls. PMID- 22308851 TI - Modifiable factors associated with low bone mineral content in underprivileged premenarchal Indian girls. AB - Low adolescent peak bone mass is associated with bone problems in adulthood. Our aim was to assess underprivileged premenarchal Indian girls for low bone mineral content and to study the influence of anthropometric, lifestyle factors on bone health. Data on anthropometry, diet, lifestyle, total body bone mineral content (TBBMC), bone area, bone mineral density, and biochemical parameters [parathyroid hormone, vitamin D (25OH-D), calcium, and zinc] were assessed in 214 premenarchal girls (8-12 years). Compared with the Indian reference database, 15.6% girls had TBBMC for age Z-scores below -2 and 37.5% had Z-scores between -2 and -1. The TBBMC for total body bone area Z-scores were below -2 for one fifth of girls, indicating undermineralized bones. Mean rate of increase in TBBMC with age and Tanner stage was lower in our study population (11.6% and 20.7%, respectively) than reference database (14.2% and 33.4%, respectively). Low weight, 25OH-D, and intake of protein, calcium, and zinc adversely affected TBBMC (p < 0.05). Many underprivileged premenarchal Indian girls are at risk of achieving low bone mass. Steps to improve underweight, 25OH-D, intakes of protein, calcium, and zinc might improve bone health. PMID- 22308852 TI - Effect of GnRH analogue on height potential in patients with severe growth hormone insensitivity syndrome treated with IGF-I. AB - Children with growth hormone insensitivity syndrome (GHIS) who receive insulin like growth factor 1 (IGF-1) treatment and enter puberty with inadequate height gain are unlikely to reach adult height within the normal range. Final height standard deviation score (SDS) in most treated children is < or = -5. Combining IGF-1 with gonadotrophin-releasing hormone analogue (GnRHa) therapy may help to improve their final height. Three patients on IGF-1 treatment, two with primary GHI and one with secondary GHI, were started on GnRHa therapy at the onset of puberty. Their ages ranged from 6.4 years to 12.9 years at the start of IGF-1 therapy (120 microg/kg twice daily by subcutaneous injection). Gains in height/bone age SDSs under GnRHa therapy ranged from 0 to 0.9. Growth velocity on GnRHa therapy ranged from 4 cm/year to 4.8 cm/year. Bone maturation (measured as change in bone age divided by change in chronological age, deltaBA/deltaCA) decreased after the start of GnRHa therapy. Predicted adult height (PAH) improved in two patients and was maintained in one. Bone mineral density showed gradual improvement from baseline. Treatment with GnRHa resulted in a gain in PAH. Final height results will provide the definite answer on the effectiveness of this combined treatment. PMID- 22308853 TI - Measurement of amino-terminal propeptide of C-type natriuretic peptide in patients with idiopathic short stature or isolated growth hormone deficiency. AB - OBJECTIVE: To explore the value of amino-terminal propeptide of C-type natriuretic peptide (NTproCNP) in evaluating the effectiveness of therapy with recombinant human growth hormone (rhGH) in patients with idiopathic short stature (ISS) and isolated growth hormone deficiency (IGHD). METHODS: Forty-eight prepubertal children (IGHD = 25, ISS = 23) treated for at least 1 year with rhGH were included. Insulin growth factor-1 (IGF-I) and NTproCNP serum levels were measured before starting treatment and again 6 months later. Twelve months after starting treatment, all patients were assessed and annual growth velocity (GV), height standard deviation score (HTSDS), and gain HTSDS (deltaHTSDS) were recorded. RESULTS: In the GHD group, positive relationships between GV and change of IGF-I(SDS) (deltaIGF-I(SDS)), GV and change of NTproCNP concentrations (deltaNTproCNP) were found. GH peak value was also positively associated with IGF I(SDS) and NTproCNP before therapy and deltaIGF-I(SDS) and deltaNTproCNP were positively associated. In the ISS group, GV was associated with only deltaNTproCNP. CONCLUSIONS: NTproCNP is a novel biomarker of growth as levels increase during growth-promoting treatment. Furthermore, IGF-I is also valuable in evaluating the efficacy of rhGH therapy in short stature patients. PMID- 22308854 TI - Growth hormone treatment, final height, insulin-like growth factors, ghrelin, and adiponectin in four siblings with Seckel syndrome. AB - OBJECTIVE: To report on the effect of growth hormone (GH) treatment on final height (FH) and to describe the insulin-like growth factor (IGF) system, ghrelin, and adiponectin (ADPN) in children with Seckel syndrome. SUBJECTS AND RESULTS: Four severely growth-retarded Iraqi siblings (two girls and two boys) with Seckel syndrome were referred at ages 16.5, 14.4, 12.4, and 10.4 years. They were born at term, but their growth was retarded and birth weight ranged between 1 and 1.5 kg. The children were healthy and had a normal response to GH provocative test. Long-term GH treatment of the youngest brother and sister increased the FH by 7.2 and 3.4 cm, respectively, compared with their older brother and sister. At FH, body mass index standard deviation scores (BMISDS) ranged from -3.0 to -3.9. Serum levels of immunoreactive IGF-1, bioactive IGF-1, and IGF-binding protein 3 were all within normal to high range before GH treatment and increased after GH treatment. Fasting plasma ghrelin remained severely reduced. Despite low BMISDS, plasma ADPN was moderately reduced and showed an almost complete absence of the low-molecular-weight subform. CONCLUSION: This is the first report on the effect of GH treatment on FH in children with Seckel syndrome. GH may have increased FH. In addition to growth defects and reduced BMISDS, patients with Seckel syndrome are characterized by low fasting ghrelin levels, low total ADPN, and near deficiency of the low-molecular-weight ADPN subform. The possible significance of the hormonal changes requires further investigations. PMID- 22308855 TI - Health promotion intervention in Arab-Israeli kindergarten children. AB - BACKGROUND: Obesity is the most common chronic pediatric disease in westernized societies, with minorities and children from low socioeconomic status being mostly affected. Arab-Israelis are the largest minority population in Israel. OBJECTIVE: The aim of this study is to examine the prevalence of obesity and to prospectively study the effects of a health promotion, school-based intervention on nutrition and physical activity knowledge and preferences, anthropometric measures, and fitness in Arab-Israeli kindergarten children. PARTICIPANTS: One hundred fifty-four children completed a school year with combined dietary behavioral-physical activity intervention and were compared with 188 controls (age 4.2-6.5 years). RESULTS: The prevalence of overweight and obesity among Arab Israeli kindergarten children was 28.9%. Compared with control, the intervention led to a significantly greater (control vs. intervention, respectively, p < 0.05) increase in nutrition knowledge (51.2+/- 1.5%-48.9 +/- 1.6% vs. 48.9 +/- 1.6% 85.9 +/- 1.4%) and preferences (47.4 +/- 1.5%-47.7 +/- 1.6% vs. 45.2 +/- 1.8% 87.1 +/- 1.4%), increase in physical activity knowledge (47.2 +/- 1.3%-47.0 +/- 1.7% vs. 49.2 +/- 1.7%-90.8 +/- 1.3%) and preferences (52.3 +/- 1.3%-54.2 +/- 1.8% vs. 56.2 +/- 1.4%-92.8 +/- 1.0%), and improvement in fitness (-10.2 +/- 1.6 vs. 11.6 +/- 1.4 shuttle run laps). The intervention was associated with favorable changes in height gain (5.0 +/- 0.1 vs. 6.2 +/- 0.1cm), body mass index (BMI-0.41 +/- 0.06 vs. -0.71 +/- 0.06 kg/m2) and BMI percentile (-10.0 +/- 1.3% vs. -16.2 +/- 1.2%) in the control and intervention groups, respectively. CONCLUSIONS: A kindergarten dietary-physical activity intervention applied by the kindergarten teachers led to a decrease in BMI, BMI percentile, improved nutrition and physical activity knowledge and preferences, and improved fitness. Such programs may play important role in health promotion, prevention, and treatment of childhood obesity in minority communities from early age. PMID- 22308856 TI - Validation of automatic bone age rating in children with precocious and early puberty. AB - BACKGROUND AND AIMS: Manual bone age (BA) rating in precocious puberty (PP) is associated with considerable rater variability. The aim was to evaluate a new method for automated Greulich and Pyle (GP) BA determination in children with PP. METHODS: Seven hundred forty-one archived X-rays from 13 boys and 103 girls with PP or early puberty of various etiologies (age range at time of X-ray, 0.3-14.8 years; mean BA advancement, 2.3 years) were rated. Automatic rating (BoneXpert BA, or BXBA) was compared with the original manual GP rating (manual BA, or ManBA). X-rays where BXBA deviated from ManBA by more than 1.5 years were rerated by three raters, and the average was formed (ReferenceBA). RESULTS: All 741 X rays, except nine (three images had poor quality and six were from children with a chronological age younger than 1.5 years), were analyzed automatically. The mean difference of BXBA-ManBA was -0.19 years; the SD of the differences was 0.76 years (95% confidence interval 0.72-0.80). ReferenceBA was determined for 41 images. A discrepancy from ReferenceBA greater 1.5 years was found in four images against BXBA and in 10 images against ManBA. CONCLUSION: Automated BA is efficient and reliable in children with PP. PMID- 22308857 TI - Interrelationship of carpal angle and bone age in children of different generations: a retrospective study. AB - BACKGROUND: Carpal angle measurement is one of the anthropometrical methods to evaluate the maturation of children. OBJECTIVE: To discuss the relationship between bone age and carpal angle in the maturation of children of two different generations. SUBJECTS AND METHODS: The first group (mid-1960s group) includes 521 Taiwanese children, 196 boys and 325 girls, growing during the agricultural period (between 1966 and 1967). The second group (mid-2000s group) includes 326 children, 74 boys and 252 girls, growing during the mid-2000s. The bone age of both groups was assessed by two leading physicians, and the carpal angle was measured by two senior radiologists. The Mann-Whitney U-test was used to compare the relationship of carpal angle and bone age among eras, sexes, and chronological ages. RESULTS: According to the same chronological age and sexes, the carpal angle of those in the mid-2000s group was larger than that of the mid 1960s group. In addition, in the same chronological age, the results also show that the mean carpal angle of girls in both generations was larger than that of boys. However, it is notable that the carpal angle of boys in the mid-2000s group is larger than that of girls in the mid-1960s group. Furthermore, by comparing the environmental condition, we suspect that the differences between carpal angles of both generation children are caused by the great changes in socioeconomic and nutrition status in Taiwan. CONCLUSION: The study presents a quantitative comparison of carpal angle between two generations of Taiwanese. The preliminary result indicates that the carpal angle for the mid-2000s group is larger than that for the mid-1960s groups. PMID- 22308858 TI - Clinical characteristics of recessive and dominant congenital hyperinsulinism due to mutation(s) in the ABCC8/KCNJ11 genes encoding the ATP-sensitive potasium channel in the pancreatic beta cell. AB - BACKGROUND: Recessive mutations in ABCC8/KCNJ11 of beta-cell K(ATP) channel generally cause severe medically unresponsive hyperinsulinemic hypoglycemia (HH). Rarer dominant mutations in these genes have been described that mostly cause milder, medically responsive congenital hyperinsulinism. Rarer dominant mutations in these genes have been described that mostly cause milder, medically responsive congenital hyperinsulinism. To date the phenotype of patients with dominant mutations seems to be different from those with recessive mutations as the majority of patients are responsive to diazoxide therapy. Controversy exists on whether these dominant ABCC8 or KCNJ11 genes mutations predispose to diabetes mellitus in adulthood or not. SUBJECTS: We report the clinical and genetic characteristics of five patients with neonatal HH, three had recessively inherited K(ATP) channel mutations and two with a dominantly acting mutation. As a result of failure to medical therapy, patients with recessive K(ATP) channel mutations underwent a near total pancreatectomy. Two siblings with a novel dominant mutation showed good response to medical treatment. Although the HH remitted in early infancy, they became diabetic at the prepubertal age. Their mother, maternal aunt and maternal grandfather had the same mutation without any medical history of neonatal HH. CONCLUSION: The clinical presentation of our two patients with a dominant ABCC8 mutation was milder than that of patients with the resessive form of the disease as they responded well to medical management. PMID- 22308859 TI - Use of nocturnal melatonin concentration and urinary 6-sulfatoxymelatonin excretion to evaluate melatonin status in children with severe sepsis. AB - The aim of this study was to evaluate whether nocturnal melatonin concentration (NMC) and urinary 6-sulphatoxymelatonin (aMT6s) excretion can predict melatonin status in patients with severe sepsis in the pediatric intensive care unit (PICU). Blood samples for the determination of NMC were obtained from each patient at 3 a.m. Urine samples for the determination of aMT6s excretion were obtained from each patient at 12 h intervals. We obtained 89 blood and 178 urine samples from 23 septic patients, and 52 blood and 104 urine samples from 13 non septic patients. The NMC of septic patients in a state of septic shock was significantly higher than that of septic patients not in septic shock (p = 0.017) and those of non-septic patients (p = 0.019). In contrast, there was no significant difference for nocturnal (NaMT6s) and total aMT6s (TaMT6s) excretion between septic patients with and without septic shock and non-septic patients (p > 0.05). The NMC was significantly higher in septic patients in shock with and without hepatic dysfunction (HD) than in non-septic patients (p = 0.004 and p = 0.024, respectively). NaMT6s and TaMT6s excretion was significantly lower in septic patients with HD than in septic patient without HD (p = 0.040 and p = 0.029, for NaMT6s and TaMT6s, respectively). Our results showed that an elevated NMC may not reflect an increased MT production in septic patients in septic shock. It seems that, to evaluate the melatonin status of septic PICU patients, it is necessary to collect both serum and urine samples. PMID- 22308860 TI - Primary ovarian dysfunction after hematopoietic stem cell transplantation during childhood: busulfan-based conditioning is a major concern. AB - We evaluated the incidence of patient/treatment factors associated with primary ovarian failure (POF) after hematopoietic stem cell transplantation (HSCT) during childhood. Fifty girls over 12 years of age (15.0 +/- 2.2) who were referred to the pediatric endocrinology clinic between March 2002 and March 2010 after HSCT at the Catholic HSCT center were enrolled in the study. In total, 36 (72%) out of 50 patients developed POF. Twenty-three patients were diagnosed and treated as chronic graft-versus-host disease. As preparative regimens for HSCT, 23 patients received total body irradiation (TBI)-based regimen, 19 received busulfan (BU) based regimen, 4 received both BU- and TBI-based, and 4 received reduced intensity conditioning regimen. In a univariate logistic regression analysis, the BU-based regimen (p = 0.028) showed a strong relationship with POF. The incidence of POF according to the route of BU administration, between orally and intravenously, were not different (p = 0.435). These results emphasize the importance of monitoring these patients at regular intervals and the need to develop complementary HSCT protocols for preventing POF in children. PMID- 22308861 TI - Vitamin D status and insulin requirements in children and adolescent with type 1 diabetes. AB - BACKGROUND: Vitamin D and its active form are potent immunomodulators and are known to play an important role in the glucose/insulin metabolism. Studies on type 2 diabetes mellitus (T2DM) have shown that vitamin D increases insulin efficacy; however, there are no studies that define a similar relationship in type 1 diabetes mellitus (T1DM). The aim of this study was to investigate the relation between serum vitamin D levels and the insulin requirement used in children with T1DM. SUBJECTS AND METHODS: A total of 100 patients with T1DM aged 4.7-19.9 years were included in the study. Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D (25OHD), and 1,25 dihydroxyvitamin D were measured. A serum 25OHD level of < 10 ng/mL was accepted as vitamin D deficiency, whereas < 20 ng/mL was accepted as vitamin D insufficiency. RESULTS: We found vitamin D deficiency in 28% and vitamin D insufficiency in 43% of our patients, whereas 29% had normal serum 25OHD levels. The insulin requirement of patients with a serum 25OHD level below 10 ng/mL were significantly higher than those of patients with a serum 25OHD level above 10 ng/mL (p = 0.012). This result did not change in those with diabetes duration of over 1 year. There was weak correlation between the daily insulin requirements and serum vitamin D levels (r = -0.212, p = 0.032). CONCLUSION: We found a significantly higher insulin requirement in T1DM children with decreased serum 25OHD levels and decreased insulin sensitivity. We recommend checking the level of serum 25OHD in children with diabetes and starting treatment if it is deficient/inadequate. PMID- 22308862 TI - Homozygosity for two missense mutations in the leptin receptor gene (P316:W646C) in a Turkmenian girl with severe early-onset obesity. AB - Leptin receptor gene mutations are a very rare cause of severe early-onset obesity. They are also associated with lack of pubertal development and intense hyperphagia. Presented here is a case of a 6-year-old Turkmenian girl with monogenic obesity due to a congenital deficiency of the leptin receptor. She was born from a consanguineous marriage of second cousins after 40 gestational weeks following an uncomplicated pregnancy. Her birth weight was 3500 g. However, rapid weight gain was observed after 6 months. On presentation she was 130 cm tall [> 97th percentile; standard deviation score (SDS): +2], with a weight of 90 kg (> 97th percentile; SDS: +5.3) and a body mass index (BMI) of 53.2 kg/m2 (SDS: +3.6). Results of genetic evaluation revealed the patient to be homozygous for two missense mutations in the leptin receptor gene (P316T;W646C) resulting in complete loss of leptin receptor function. Both parents were heterozygous for the same pair of missence mutations. PMID- 22308863 TI - A 3-year-old girl with Graves' disease with hypoglycemia following transient adrenal hyporesponsiveness. AB - A 3-year-old girl with Graves' disease developed a generalized convulsion as a result of hypoglycemia (25 mg/dL). At the time of the hypoglycemic seizure, her plasma adrenocorticotropin (ACTH) level (1460 pg/mL) was extremely high, but her serum cortisol level (28.4 microg/dL) was relatively low given the severe stress. The cortisol-releasing hormone (CRH) provocation test done after thyroid function had improved revealed normal ACTH and cortisol responses. Since there was no other cause of hypoglycemia, such as hyperinsulinemia, long-term starvation, suddenly advanced emaciation, or prolonged fasting, it was suspected that the transient adrenal hyporesponsiveness was the main cause of hypoglycemia. PMID- 22308864 TI - Papillary carcinoma masquerading as clinically toxic adenoma in very young children. AB - BACKGROUND: Autonomously functioning thyroid nodules (AFTN) are extremely rare in children. Malignancy may be rarely found in hyperfunctioning 'hot' nodules in adults. However, there are limited reports of AFTNs in young children presenting as or developing malignancy in future. We report here two young children aged < 6 years old at the time of diagnosis as having an AFTN, which eventually turned out to be papillary carcinoma of thyroid (PTC) on follow-up. PATIENT FINDINGS: A 2 month-old baby had a right-sided neck swelling since birth. On examination, the baby had clinical and biochemical features of thyrotoxicosis. On sonography, and subsequently on 99mTc-pertechnetate thyroid scan, a hot nodule was found. Patient was treated with carbimazole for 5 years. In spite of euthyroidism achieved, the nodule continuously grew in size. Thyroid cytology was inconclusive, hence hemithyroidectomy was performed and histopathology turned out to be PTC. Another 5-year-old female child had a large right-sided AFTN on thyroid scan. She was treated with radioiodine; however, like the previous case, the nodule started growing in size. She subsequently underwent near total thyroidectomy and histology was reported as PTC. CONCLUSION: In the light of this report that shows that solitary hyperfunctioning nodules in very young children have high chance of malignancy, we recommend hemithyroidectomy as the treatment of choice. PMID- 22308865 TI - Hyperandrogenism in a set of triplets with modification of clinical course by hyperthyroidism. AB - We report hyperandrogenism with severe acne, hirsutism and alopecia in a set of non-obese triplet sisters presenting at an early age. Interestingly, one of the triplets had hyperthyroidism and had significantly lower androgen level as well as hirsutism compared to her sisters. Treatment of hyperthyroidism with radioiodine ablation led to significant elevation of androgen levels and worsening of hirsutism suggesting that hyperthyroidism masks the biochemical and clinical expression of hyperandrogenism in susceptible females. PMID- 22308866 TI - A case of Langerhans cell histiocytosis with thyroid involvement. AB - Thyroid involvement with Langerhans cell histiocytosis (LCH) is very rare. We report here the case of a 15-year-old female patient with LCH affecting the thyroid gland. She was referred to the department of pediatric endocrinology for secondary amenorrhea. Prior to the diagnosis of LCH, the patient had symptoms of diabetes insipidus (DI) and amenorrhea. The mean time from symptom onset to diagnosis was 2 years. On physical examination the patient had grade 2 goiter, and ultrasound showed bilateral multiple hypoechoic nodules and thyroid heterogeneity. Biochemical analysis indicated central diabetes insipidus and panhypopituitarism. Magnetic resonance imaging (MRI) demonstrated a mass lesion involving the hypothalamus, which appeared iso- to hypo-intense on T2-weighted images and had an intense postcontrast enhancement on T1-weighted images. Nodular goiter coinciding with a hypothalamic mass suggested LCH, and an excisional biopsy was performed. Histological evaluation of the thyroid gland revealed extensive involvement by LCH, and this was confirmed by immunohistochemical analysis showing S-100 protein and CD1a positive Langerhans cells that were weakly positive for CD68. LCH should be considered in the differential diagnosis of a diffusely enlarged firm and irregular thyroid gland and posterior or anterior pituitary dysfunction. PMID- 22308867 TI - Congenital rhabdomyosarcoma, central precocious puberty, hemihypertrophy and hypophosphatemic rickets associated with epidermal nevus syndrome. AB - We describe a newborn girl with right-sided extended epidermal nevus, congenital rhabdomyosarcoma of the inguinal area at birth who had developed central precocious puberty, hemihypertrophy and vitamin D3-responsive hypophosphatemic rickets at the age of 14 months. Our patient demonstrates a much broader and polymorphic spectrum of organ systems involvement in epidermal nevus syndrome at a very early age of her life. PMID- 22308868 TI - Precocious puberty and empty sella syndrome in a girl cured of acute lymphoblastic leukemia. AB - We describe a case of precocious puberty in a girl treated with chemoradiotherapy according to the Italian Association of Pediatric Hematology and Oncology ALL 9503 protocol for acute lymphoblastic leukemia (ALL) from the age of 15 months until the age of 3 years and 4 months. The patient was treated with chemotherapy and cranial irradiation (18 Gy in 12 fractions). At 7 years of age, during topical estrogenic treatment for congenital adhesions of the labia minora, she showed bilateral breast development that evolved into precocious puberty. A magnetic resonance imaging of the brain showed an "empty sella" (ES); the etiology of the ES, and the consequent precocious puberty, being presumably iatrogenic. Children treated with cranial radiotherapy should be carefully checked for signs of precocious puberty and the exogenous administration of estrogens should be avoided, as far as possible, because these could act as a trigger factor in a population at higher risk of precocious puberty. PMID- 22308869 TI - Sex of rearing seems to exert a powerful influence on gender identity in the absence of strong hormonal influence: report of two siblings with PAIS assigned different sex of rearing. AB - There is an ongoing debate regarding the relative contribution of nurture over nature in development of gender identity. Patients with partial androgen insensitivity syndrome (PAIS) have ambiguous genitalia and are known to be reared as male or female. Familial cases of PAIS sharing common hormonal defects are usually reared in the same sex. Here, we describe two siblings with PAIS, one reared as a male and the other as female. These two siblings presented at adolescence. Gender identity was concordant with the sex of rearing for both. The male sibling was distressed with gynecomastia that had disrupted his social life. The sex of rearing seems to have played a predominant role in the formation of gender identity in these two patients with PAIS. PMID- 22308870 TI - Transient neonatal diabetes with two novel mutations in the KCNJ11 gene and response to sulfonylurea treatment in a preterm infant. AB - Neonatal diabetes mellitus (NDM) is a rare condition that can be either transient or permanent. K(ATP) channel (Kir6.2 or SUR1) mutation, chromosome 6 abnormalities, insulin, or glucokinase gene mutations can lead to isolated NDM. Cases caused by Kir6.2 mutation usually result in permanent NDM (PNDM) rather than transient NDM (TNDM). The majority of patients with the Kir6.2 or SUR1 mutation can be successfully managed with a sulfonylurea agent, without the need for insulin. We report a preterm male with NDM having two novel missense mutations, E322A and D352H, in the KCNJ11 gene. At 2 months of age, successful transition from insulin to glibenclamide (glyburide) therapy of the patient was managed. At 5 months of age, his diabetes went in to remission. PMID- 22308871 TI - Persistent hypoglycemia caused by umbilical arterial catheterization. AB - Hypoglycemia as an umbilical artery catheter (UAC) complication is rare. We present a neonate with hyperinsulinemic hypoglycemia due to a high-positioned UAC used inadvertently for parenteral nutrition. The aim of this report is to increase physicians' awareness of the possibility of this rare complication. PMID- 22308872 TI - Congestive heart failure as an initial manifestation of reninoma. AB - Reninoma or juxtaglomerular cell tumor (JCT) of the kidney is a rare but curable cause of severe hypertension. We report a case of reninoma in an 18-year-old woman. Interestingly, she initially presented with dilated cardiomyopathy, without any relevant history or signs of hypertension. Malignant hypertension, one of the cardinal signs of JCT, did not become apparent in the patient until several months later. Following a thorough evaluation, we detected a small mass in the left renal cortex as well as elevated plasma renin activity, which suggested the presence of a renin-producing tumor in the kidney. The patient's blood pressure and plasma renin activity rapidly declined after a successful laparoscopic partial nephrectomy. We postulate that hyperreninemic hyperaldosteronism followed by fluid retention caused a sudden severe increase in ventricular afterload and subsequent congestive heart failure in this patient. PMID- 22308873 TI - Multiple pterygium syndrome: mimicking the findings of Turner syndrome. AB - Multiple pterygium syndrome (MPS or Escobar syndrome) is a rare, generally autosomal recessive disorder characterized by multiple congenital joint contractures and multiple skin webs. An 11.5-year-old girl with a working diagnosis of Turner syndrome (TS) was referred for her phenotypic features and growth retardation. Pterygium of the neck, low posterior hairline, widely spaced nipples, cubitus valgus, upslanting palpebral fissures, hypertelorism, micrognathia, low-set ears, downturning corners of the mouth, long philtrum, high arched palate, digital and intercrural webbings, and aplasia of the labia majora were indicative of MPS (Escobar syndrome). Her mental status was normal. Facial asymmetry was present due to cervical webs. Normal karyotype, gonadal functions, and cardiac and urinary system findings helped in excluding TS. Genetic diseases associated with skin webs were revised in differential diagnosis. PMID- 22308874 TI - A neonate with contiguous deletion syndrome in XP21. AB - INTRODUCTION: We report a case of a male infant with the association of pseudohypertriglyceridemia, hypoadrenalism (hyponatremia, hyperpotasemia, dehydration), high creatine phosphokinase level (possible Duchenne's muscular dystrophy, DMD) and diagnosed contiguous gene deletion syndrome in Xp21. CASE REPORT: A 1-month-old male term infant was referred due to no weight gain. The examination revealed dehydration (decreased skin turgor), scrotal hyperpigmentation and hypotonia. Laboratory findings showed hyponatremia of 124 mmol/L, hyperpotasemia of 6.9 mg/dL, high creatine phosphokinase level of 7019 IU/L, and high blood triglyceride level of 1244 mg/dL. There was no deletion detected in the dystrophin gene with the study investigating selected exons, no dystrophin staining and nonspecific atrophic findings in the muscle biopsy. Further laboratory findings defined high glycerol concentrations both in blood and in urine that were compatible with a glycerol kinase deficiency (GKD). Array CGH study confirmed the existence of a deletion in Xp21 of the genes responsible for DMD, GKD and the congenital adrenal hypoplasia (gene DAX1 or NROB1 gene: Xp21.3-21.2). The infant showed good response to mineralocorticoid therapy, hyponatremia resolved and gained weight. CONCLUSION: Physicians should consider contiguous gene deletion syndrome in Xp21 in the infants with myopathic compromise, increased levels of creatine phosphokinase and pseudohypertriglyceridaemia to be able to prevent and treat the metabolic complications. Furthermore, geneticists should take into account to design routine deletion studies including the promoter region in this disorder. PMID- 22308875 TI - Kocher-Debre-Semelaigne syndrome with pericardial effusion. AB - Kocher-Debre-Semelaigne syndrome (KDSS) is a rare association of muscular pseudohypertrophy and hypothyroidism in children. We report an 11-year-old female child with hypothyroidism and limb muscle pseudohypertrophy with pericardial effusion. The patient presented with hypertrichosis only. She had dull facies and marked hypertrophy of both calves and cervical muscles. Pericardial effusion was confirmed on investigations. Muscle pseudohypertrophy was a striking feature, and hypothyroidism was confirmed on thyroid studies. Pericardial effusion is known in hypothyroidism but has been very rarely reported with KDSS. PMID- 22308876 TI - Accountable care organizations: opportunities for social workers. PMID- 22308877 TI - Adherence to medication regimens among low-income patients with multiple comorbid chronic conditions. AB - This qualitative study sought to explore facilitators and barriers to adherence to multiple medications among low-income patients with comorbid chronic physical and mental health conditions. The 50 focus group participants identified personal/contextual and health system factors as major impediments to adherence to multiple medications. These factors included medication side effects, fear of harm from medication, fear of dependence on medication, complex instructions, suboptimal communications with doctor, suspicion about doctors' and pharmaceutical companies' motives in prescribing medication, and the high cost ofmedications. Participants also identified motivators, both internal (self initiated) and external (initiated by family, doctor, support groups),to ensure adherence to multiple medications. These motivators included self-discipline, sense of personal responsibility, faith, support from family members and doctors, and focused health education and self-management support. Three themes emerged that enhanced understanding of the complexity of adherence to multiple medications: (1) reaching one's own threshold for medication adherence, (2) lack of shared information and decision making, and (3) taking less than the prescribed medication. Further analysis of the data revealed that the patients perceived a lack of shared decision making in the management of their comorbid chronic conditions and their medication regimen. PMID- 22308878 TI - Using appreciative inquiry to facilitate implementation of the recovery model in mental health agencies. AB - This article describes an organizational development tool called appreciative inquiry (AI) and its use in mental health to aid agencies implementing recovery model services. AI is a discursive tool with the power to shift dominant organizational cultures. Its philosophical underpinnings emphasize values consistent with recovery: community, empowerment, and positive focus. Recent research in the field of mental health demonstrates the salience of organizational cultural context in affecting new service adoption. This article explores how AI could be helpful in shifting an organization's culture to render it compatible with recovery through descriptions of two mental health centers' use of the tool. The experiences described indicate that AI, if used consistently, empowers staff. The article concludes with consideration of the implications of this empowerment for recovery model implementation and directions for future research. PMID- 22308879 TI - What social workers in health care should know about lupus: a structural equation model. AB - This article reports on findings from a cross-sectional study (N=378) of patients living with systemic lupus erythematosus (SLE). The purpose of this study was to identify and clarify the unique psychosocial challenges for those living with lupus. The specific analysis will help to develop a model to determine how different factors influence SLE patients' psychosocial needs. Key findings indicate that the highest general causes of depressive and anxious feelings were changes in appearance due to SLE and limitations in physical abilities due to SLE. The more chronic the symptoms, the more likely it was that feelings of depression would ensue. The more education subjects had, the less likely they were to report feeling depressed or anxious about their SLE challenges. Those with no health care insurance reported the highest levels of depressive and anxious feelings, those with Medicaid reported the second highest, and those with Medicare reported the least SLE-related depression and anxiety. The great majority of SLE patients on medications experienced a wide range of side effects, the most prominent being hair loss. These findings can inform policy and programs as well as clinical initiatives for those affected by SLE. PMID- 22308880 TI - Parent and health care professional perspectives on family-centered care for children with special health care needs: are we on the same page? AB - A family-centered approach to health care for children with special health care needs (CSHCN) is widely acknowledged as the ideal model of service delivery, but less is known about the actual practice of family-centered care (FCC), especially from the viewpoints of parents and health care professionals. This cross sectional research compared parent and health care professional perspectives on the degree to which FCC is being provided at a large, urban hospital in the United States. The Measure of Process of Care (MPOC) was administered to a representative sample of 92 parents of CSHCN; a convenience sample of 43 health care professionals completed the service provider version of the MPOC. A mixed model analysis of variance was conducted to test for group differences on matched domain scores of the MPOC. No significant differences emerged between the two stakeholder groups, but significant differences were detected among the four domain scores. The data suggest that health professionals are generally meeting families' needs for specific communication and are respectful of parents' expertise. However, parents and professionals alike indicated the need for continued professional growth in the area of providing holistic, comprehensive services to advance FCC. PMID- 22308881 TI - Use of distress thermometers in an outpatient oncology setting. PMID- 22308882 TI - Mild traumatic brain injury: a silent epidemic in our practices. PMID- 22308883 TI - Using the International Classification of Functioning, Disability and Health in social work settings. PMID- 22308884 TI - LGBTQ capacity building in health care systems: a social work imperative. PMID- 22308885 TI - Visual search in the real world: evidence for the formation of distractor representations. AB - Visual search in the real world often requires that we search the same environment a number of times for different targets. What is the fate of information about fixated distractor objects during these searches? Here, participants searched the same array of real objects on a tabletop twice for two different targets successively whilst wearing a head-mounted eye-tracker. We found that fixating an object when it was a distractor in the first search facilitated search for that same object when it became the target in the second search. The results suggest that the location and identity of fixated distractor objects are represented to a level that guides subsequent searches, even when this information is not required at the time of fixation. PMID- 22308886 TI - An advantage for active versus passive aperture-viewing in visual object recognition. AB - In aperture viewing the field-of-view is restricted, such that only a small part of an image is visible, enforcing serial exploration of different regions of an object in order to successfully recognise it. Previous studies have used either active control or passive observation of the viewing aperture, but have not contrasted the two modes. Active viewing has previously been shown to confer an advantage in visual object recognition. We displayed objects through a small moveable aperture and tested whether people's ability to identify the images as familiar or novel objects was influenced by how the window location was controlled. Participants recognised objects faster when they actively controlled the window using their finger on a touch-screen, as opposed to passively observing the moving window. There was no difference between passively viewing again one's own window movement as generated in a previous block of trials versus viewing window movements that had been generated by other participants. These results contrast with those from comparable studies of haptic object recognition, which have found a benefit for passive over active stimulus exploration, but accord with findings of an advantage of active viewing in visual object recognition. PMID- 22308887 TI - The influence of selective attention to auditory and visual speech on the integration of audiovisual speech information. AB - Conflicting visual speech information can influence the perception of acoustic speech, causing an illusory percept of a sound not present in the actual acoustic speech (the McGurk effect). We examined whether participants can voluntarily selectively attend to either the auditory or visual modality by instructing participants to pay attention to the information in one modality and to ignore competing information from the other modality. We also examined how performance under these instructions was affected by weakening the influence of the visual information by manipulating the temporal offset between the audio and video channels (experiment 1), and the spatial frequency information present in the video (experiment 2). Gaze behaviour was also monitored to examine whether attentional instructions influenced the gathering of visual information. While task instructions did have an influence on the observed integration of auditory and visual speech information, participants were unable to completely ignore conflicting information, particularly information from the visual stream. Manipulating temporal offset had a more pronounced interaction with task instructions than manipulating the amount of visual information. Participants' gaze behaviour suggests that the attended modality influences the gathering of visual information in audiovisual speech perception. PMID- 22308888 TI - Distractor filtering in media multitaskers. AB - A growing amount of modern media is consumed simultaneously, a phenomenon known as 'media multitasking'. Individuals who regularly engage in this activity, heavy media multitaskers (HMMs), are more affected by irrelevant information that can intrude into a primary task than are light media multitaskers (LMMs--Ophir et al, 2009 Proceedings of the National Academy of Sciences of the USA 106 15583). However, the locus of this deficit is unknown, as previous research is consistent with both memory and attentional explanations. Here, we isolated attentional processes by employing a singleton distractor task with low working-memory demands. In this task, LMMs used top-down information to improve their performance, yet HMMs did not. This difference in performance in an established attentional capture task argues for the presence of attentional differences in HMMs and is consistent with the idea that HMMs maintain a wider attentional scope than LMMs, even when instructed otherwise. PMID- 22308889 TI - Comparisons of complex sounds across extended retention intervals survives reading aloud. AB - A simple experimental arrangement is designed to foil verbal rehearsal during an extended (from 5 to 30 s) retention interval across which participants attempt to discriminate two periodic complex sounds. Sounds have an abstract timbre that does not lend itself to verbal labeling, they differ across trials so that no 'standard' comparison stimulus is built up by the participants, and the spectral change to be discriminated is very slight and therefore does not shift the stimulus into a new verbal category. And, crucially, in one experimental condition, participants read aloud during most of the retention interval. Despite these precautions, performance is robust across the extended retention interval. The inference is that one form of auditory memory does not require verbal rehearsal. Nevertheless, modest forgetting occurred. Whatever form memory takes in this situation, it is not totally secure from disruption. PMID- 22308890 TI - Perceiving musical individuality: performer identification is dependent on performer expertise and expressiveness, but not on listener expertise. AB - Can listeners distinguish unfamiliar performers playing the same piece on the same instrument? Professional performers recorded two expressive and two inexpressive interpretations of a short organ piece. Nonmusicians and musicians listened to these recordings and grouped together excerpts they thought had been played by the same performer. Both musicians and nonmusicians performed significantly above chance. Expressive interpretations were sorted more accurately than inexpressive ones, indicating that musical individuality is communicated more efficiently through expressive performances. Furthermore, individual performers' consistency and distinctiveness with respect to expressive patterns were shown to be excellent predictors of categorisation accuracy. Categorisation accuracy was superior for prize-winning performers compared to non winners, suggesting a link between performer competence and the communication of musical individuality. Finally, results indicate that temporal information is sufficient to enable performer recognition, a finding that has broader implications for research on the detection of identity cues. PMID- 22308891 TI - Quantitative relation between server motion and receiver anticipation in tennis: implications of responses to computer-simulated motions. AB - The purpose of this study was to determine the quantitative relationships between the server's motion and the receiver's anticipation using a computer graphic animation of tennis serves. The test motions were determined by capturing the motion of a model player and estimating the computational perturbations caused by modulating the rotation of the player's elbow and forearm joints. Eight experienced and eight novice players rated their anticipation of the speed, direction, and spin of the ball on a visual analogue scale. The experienced players significantly altered some of their anticipatory judgment depending on the percentage of both the forearm and elbow modulations, while the novice players indicated no significant changes. Multiple regression analyses, including that of the racket's kinematic parameters immediately before racket-ball impact as independent variables, showed that the experienced players demonstrated a higher coefficient of determination than the novice players in their anticipatory judgment of the ball direction. The results have implications on the understanding of the functional relation between a player's motion and the opponent's anticipatory judgment during real play. PMID- 22308892 TI - Consistent air flow to the face facilitates vection. AB - We examined whether a somatosensory cue suggesting forward self-motion facilitated vection. We provided a consistent air flow to subjects' faces by using an electric fan.Vection strength was increased when the air flow was provided. PMID- 22308893 TI - The mental number line in depth revealed by vection. AB - To explore how numbers are represented in depth in our mental space, we asked participants to sequentially speak random numbers while they observed forward/backward vection. We found that participants tended to generate larger numbers when they perceived backward self-motion. The results suggest that numerical magnitudes were topographically mapped onto our mental space from front to rear in an ascending order. PMID- 22308894 TI - Touching my face with my supernumerary hand: a cheeky illusion. AB - A self-touch paradigm elicits a surprising illusion. With the participant's eyes closed, the examiner guides the participant's right index finger to administer strokes and taps to the right side of the participant's face. At the same time, the examiner strokes and taps the corresponding location on the left side of the participant's face. Although the participant administered touch to only the right side of the face, this paradigm elicited the illusion of self-touch to both sides of the face, and the illusion often implicated a third, disconnected or disembodied, hand. We propose an explanation, and draw parallels with the phenomenon of supernumerary phantom limb. PMID- 22308895 TI - Training synaesthesia. AB - Synaesthetic inducers such as graphemes are typically cultural artifacts. Thus, a learning component seems evident in synaesthesia (Simner et al, 2009 Brain 132 57 64). Normally, synaesthetes report to have their experiences since they can remember. Nevertheless, a recent training study suggests that synaesthesia can be mimicked in non-synaesthetes. To date, the role of learning during the development of synaesthesia is still debated. It is not clear whether synaesthesia can be learned or trained at all. To address this question, we compared a non-adaptive and an adaptive training for their effectiveness. We assessed their impact on two types of priming tasks, before and after the training. We found stronger priming in the adaptive training group suggesting that adaptive training is more efficient to mimic synaesthesia. PMID- 22308896 TI - Body-based perceptual rescaling revealed through the size-weight illusion. AB - An embodied approach to the perception of spatial layout contends that the body is used as a 'perceptual ruler' with which individuals scale the perceived environmental layout. In support of this notion, previous research has shown that the perceived size of objects can be influenced by changes in the apparent size of hand. The size-weight illusion is a well known phenomenon, which occurs when people lift two objects of equal weight but differing sizes and perceive that the larger object feels lighter. Therefore, if apparent hand size influences perceived object size, it should also influence the object's perceived weight. In this study, we investigated this possibility by using perceived weight as a measure and found that changes in the apparent size of the hand influence objects' perceived weight. PMID- 22308897 TI - Preference for symmetry: only on mars? AB - Preference for symmetry is a robust bias found throughout the animal kingdom. In humans, the bias for symmetry has been documented in numerous domains, including faces and visual patterns. The function of this potent aesthetic bias still eludes us, but prominent accounts focus on its role in mate selection and perceptual fluency. Previous studies have shown that both males and females find symmetrical faces to be more attractive, but here we show that the preference for symmetry in neutral stimuli (ie everyday and meaningless visual objects) is, on the other hand, unique to male participants. Our findings indicate that symmetry preference cannot be explained exclusively by perceptual or computational efficiency, because such an account is domain-independent yet females did not show any bias for the objects tested here. Further studies are needed to elucidate the utility of the male preference for visual object symmetry. PMID- 22308898 TI - The Thatcher effect in biological motion. AB - We demonstrate the Thatcher effect in biological-motion displays and show that it is primarily a result of the moving, and not static, cues in the display. PMID- 22308899 TI - Mask in the mirror: the living mask illusion. PMID- 22308900 TI - The missing sense modality: the immune system. AB - The five senses were handed down by Aristotle. I argue that it has only taken two millennia to recognize that the immune system has been the hidden sensory modality. The immune system completes the range of operation allowing detection of meaningful entities at all distances, from very near to very far. It also withstands the often implicit criteria for being a sense modality. Finally, cross modal interactions between the immune system and vision and other sense modalities should be possible, opening up new research directions. PMID- 22308901 TI - Electron spin resonance. Part two: a diagnostic method in the environmental sciences. AB - A review is presented of some of the ways in which electron spin resonance (ESR) spectroscopy may be useful to investigate systems of relevance to the environmental sciences. Specifically considered are: quantititave ESR, photocatalysis for pollution control; sorption and mobility of molecules in zeolites; free radicals produced by mechanical action and by shock waves from explosives; measurement of peroxyl radicals and nitrate radicals in air; determination of particulate matter polyaromatic hydrocarbons (PAH), soot and black carbon in air; estimation of nitrate and nitrite in vegetables and fruit; lipid-peroxidation by solid particles (silica, asbestos, coal dust); ESR of soils and other biogenic substances: formation of soil organic matter carbon capture and sequestration (CCS) and no-till farming; detection of reactive oxygen species in the photosynthetic apparatus of higher plants under light stress; molecular mobility and intracellular glasses in seeds and pollen; molecular mobility in dry cotton; characterisation of the surface of carbon black used for chromatography; ESR dating for archaeology and determining seawater levels; measurement of the quality of tea-leaves by ESR; green-catalysts and catalytic media; studies of petroleum (crude oil); fuels; methane hydrate; fuel cells; photovoltaics; source rocks; kerogen; carbonaceous chondrites to find an ESR-based marker for extraterrestrial origin; samples from the Moon taken on the Apollo 11 and Apollo 12 missions to understand space-weathering; ESR studies of organic matter in regard to oil and gas formation in the North Sea; solvation by ionic liquids as green solvents, ESR in food and nutraceutical research. PMID- 22308902 TI - Atomic evidence: the foundations of structural molecular biology. AB - Atomic structures of biomolecules have provided the experimental evidence for many of the major discoveries in molecular biology, including the basic principles of protein folding and function, modes of biological information and energy flow, and mechanisms of molecular evolution. These experimental data are freely available in online structural databases. PMID- 22308903 TI - Analysis of bacterial surface interactions using microfluidic systems. AB - Modern microbiological research has increasingly focused on the interactions between bacterial cells and the surfaces that they inhabit. To this end, microfluidic devices have played a large role in enabling research of cell surface interactions, especially surface attachment and biofilm formation. This review provides background on microfluidic devices and their use in biological systems, as well specific examples from current literature. Methods to observe and interrogate cells within microfluidic devices are described, as well as the analytical techniques that are used to collect these data. PMID- 22308904 TI - Current commentary: Can free radicals be good for you? PMID- 22308905 TI - [Historic review of minimally invasive surgery in Romania--a new surgical era]. AB - The minimally-invasive surgery developed during the last decades, having an important place within the operating techniques of many surgical specialities once high-performing instruments and devices were created. It is represented by laparoscopic, thoracoscopic, arthroscopic and endoscopic techniques (diagnostical and therapeutical). The introduction and development of such techniques at the global level allowed for them to be introduced in our country in a rather short period of time after their usage abroad. This article consists of a brief description of the minimally-invasive surgery both at the global and national level. PMID- 22308906 TI - [Old and new concepts in surgical therapy of gastroduodenal ulcers complicated or resistant to treatment]. AB - This article presents the old and the new therapeutic protocols in the gastroduodenal ulcer. In our opinion, subtotal gastric resection and bilateral subdiafragmatic vagotomy must be considered "historical" without having theoretical support in the era of the antisecretory and anti Helicobacter pylori medication, with similar or superior effects. Is considered as complete the era of the gastric large crippling resection of Pean and Billroth, as the era of Dragstedt's vagotomy and applied the new methods nonaggressive and miniminvasive. PMID- 22308907 TI - Conservative surgery for borderline ovarian tumors--emphasis on fertility preservation. A review. AB - BACKGROUND: Borderline ovarian tumors account for 15-20% of all ovarian epithelial tumors. Since their original description in 1929, our knowledge of their natural history and molecular pathology has advanced most dramatically over the last two decades. This improved knowledge of BOT has permitted to drastically decrease the therapeutics of these tumors, which remains mostly surgical. METHOD: We studied the available literature on surgical management of BOT accentuating the most important aspects on this topic: radical vs. conservative treatment, fertility preservation. RESULTS: Although there are conflicting reports about some of the aspects of surgical management of these tumors, since BOTs commonly affect women of reproductive age, who have not completed childbearing, have an excellent overall prognosis and the majority of them (approximately 50% to 85%) are stage I at diagnosis, conservative surgery (unilateral salpingo-oophorectomy or cystectomy) can be safely performed after comprehensive surgical staging, in order to preserve fertility. CONCLUSION: Conservative surgery could be safely performed in young patients treated for BOT, provided that they are carefully followed-up. PMID- 22308908 TI - [The role of multimodal analgesia in the decrease of postoperative surgical stress response in major neoplastic thoraco-abdominal surgery]. AB - A major issue of the surgical anesthetic team is the surgical stress response, with its organ disfunctions, and the postoperative pain with consequences regarding the physiopathologic and socio-economical impact associated with its inadequate therapy. According to the "fast-track" approach, multimodal analgesia has a central place, together with minimal invasive procedures. Opioid-local anesthetic association via thoracic epidural catheter, has become the "anesthetic golden standard", in major thoraco-abdominal surgery. Co-administration of i.v. non-steroid anti-inflammatory drugs, seriously decreases the inflammatory response to the surgical stress, allowing a faster recovery, an early social rehabilitation, and a decrease in morbidity and mortality associated with major neoplasic surgery. PMID- 22308909 TI - The thread-protective cell, a new cell performing multiple tasks. AB - Our research work, which has led us to discovering the new cerebral cell, has started 30 years ago. An important moment was the year 1986, when we have highlighted it for the first time, during a study upon the clarification of some undiscovered aspects of cerebral atherosclerosis. In 2006 we have initiated the publishing of our results at three congresses (Cape Town - 2006; San Diego - 2009 and Los Angeles - 2011) as well as in three Atlases, form 2006, 2008 and 2010. By means of the electronic microscope we have analyzed to this purpose alone, a number of neurosurgery patients, with 1176 cerebral, vascular, tumoral, cortical, choroid plexus tumor and infectious biopsies. The cell in question was named cordocit-protectocit (thread-protective cell) in order to highlight its morphological aspect of a belt band and its functional one, of protective element of the noble substance of the brain, acting for its defense against various aggressions, especially hemorrhagic. On this occasion we have discovered that the pia mater is made up of such protective cells, which also play a role in preventing the neuroblasts from migrating. When the chemotactants of our cells are not numerous enough, subcortical cell heterotopias will occur, at the level of the corona radiata, double cortex and other neuronal migration disorders which may generate epilepsy. Therefore, the pia mater should be considered from a cytodynamic perspective. The telocyte at the internal organs level (intestine, heart etc.) is nothing else but the interstitial cell of Cajal (ICC), described by Cajal more than 100 years ago. The ICC spontaneously initiate rhythmic electrical activity, much like the peacemaker cells of the heart. PMID- 22308910 TI - [The management of postoperative pancreatic fistulas]. AB - Postoperative pancreatic fistula is the most common major complication after pancreatic surgery and it can lead to prolonged hospital stay, increased costs and mortality. Its incidence is between 2 and 30%. We present a series of 100 successive patients, operated in our clinic for different pancreatic diseases. Among them, 21 had pancreaticoduodenectomies, 24- enucleation procedures for insulinomas or pancreatic adenomas, 31- distal pancreato-spleenectomies and in 24 cases a pancreatic abcess or pseudocyst was drained. A pancreatic fistula occurred in 21 patients (21%); we analyzed the treatment and outcome of these fistulas, according to our experience and to the International Study Group of Pancreatic Fistula (ISGPF) classification. 10 patients needed only medical treatment, while in 11 cases one/more new surgical procedure(s) was/were required. 15 patients had a favourable evolution and 6 other patients deceased. In persistent fistulas, as well as in those with a high output, the resection of the pancreatic remnant appears to be the best surgical option. PMID- 22308911 TI - Spectrum, antibiotic susceptibility and virulence factors of bacterial infections complicating severe acute pancreatitis. AB - Secondary infection of pancreatic necrotic tissue and peripancreatic fluid is a serious complication of acute pancreatitis resulting in significant morbidity and mortality. The aim of this study was to find out the spectrum of bacterial infections, their antibiotic susceptibility patterns and virulence features in patients with severe acute pancreatitis (SAP). A total of 19 patients with acute pancreatitis were consecutively selected from 153 clinical cases of septic abdominal surgical emergencies (age 29-80, 12 males, 7 females) admitted during 2009-2011, in the First Surgical Clinic of the University Emergency Hospital of Bucharest. All 19 SAP cases were submitted to pre-operatory antibiotic empiric treatment. Ten cases were culture negative, in spite of the positive microscopy registered in eight of them. The rest of nine cases were culture positive, 17 different bacterial strains being isolated and identified as belonging to eight aerobic and four anaerobic species. Polymicrobial infection was seen in six patients and the etiology was dominated by Gram-negative bacilli, followed by gut anaerobic bacteria, attesting their colonic origin. The susceptibility testing of the isolated strains confirmed in vitro in all cases the efficiency of the antibiotics that had been used in the empiric pre-operatory treatment. Out of 19 cases submitted to pre-operatory empiric treatment, 14 proved a favorable evolution and five a lethal outcome. The host depending factors (sepsis and other co-morbidities), as well as the aggressivity of the isolated microbial strains (mediated by the presence of different factors implicated in adherence, toxicity and invasion) were found to contribute to the unfavorable, even lethal clinical outcome of SAP cases. In spite of all theoretical controversies, the antibiotic therapy remains at present a very important therapeutic mean for the SAP treatment; although it cannot solve the septic necrotizing pancreatitis in 100% of cases, however, associated with the surgery and all other medical means of intensive therapy, the antibiotic treatment can influence the clinical evolution to the benefit and recovery of patients in a significant number of cases. PMID- 22308912 TI - Postradiotherapy regression--a prognostic factor in rectal neoplasm. AB - Preoperative radiotherapy is standard procedure in rectal cancer treatment protocols. Experience and analysis of clinical and laboratory features of the results of this procedure have established that the response to radiotherapy, in order to reduce the volume of tumor and adenopathies of stations I and II is highly variable, from complete disappearance of the tumor mass, to the lack of response. The response to radiotherapy in conjunction with pathological and immunohistochemical data could allow assessment of prognosis in the rectal cancer. For this purpose we have proposed conducting a clinical trial to examine the tumor grading, immunohistochemical markers, and possible genetic changes that allow assessment of the degree of post-radic regression and the postterapeutic prognosis. Based on these criteria would be possible to establish a group of regression in which the patient stands still from the pretherapeutic phase. In this way the type of the presurgical radiation would shade, sometimes this standard being made ineffective. We come with a lot preliminary statistics, with the value of working hypothesis. PMID- 22308913 TI - Mean number of lymph nodes in colonic cancer specimen: possible quality control index for surgical performance. AB - Lymphatic involvement in colonic cancer explains the need for extensive lymphadenectomy for intended curative operations. Surgical skills may determine the actual extent of the procedure and indirectly the number of lymphnodes (LN) removed from each specimen. MATERIAL AND METHODS: We looked on a series of 329 consecutive patients with colonic cancer who underwent a standardized procedure including extensive lymphadenectomy. The main endpoints were survival as well as the number of LN and the mean number of RESULTS: Differences in Kaplan-Meyer survival curves between average and high performance colectomies have been identifled for right colectomies both in stage II (85.7% vs 64.7%) as well in stage III (71.4% vs 56.5% 5-year survival), and also in stage II for segmental colectomies (85.7% vs 78.9%), showing a definitive advantage in survival for patients operated by surgeons with a mean LN retrieval above cutoff values. CONCLUSIONS: our study suggests that the mean number of LN retrieved from the surgical specimen can be used to evaluate surgical performance in colonic cancer, and may reflect in postoperative survival. However care should be taken when extrapolating these data as surgeon-independent factors such as protocols for LN harvesting may be different in other institutions and will influence results. PMID- 22308914 TI - [Thyroid cancer--the malignant lesions in the contralateral lobe]. AB - AIM: This study analysed the frequency of the malignant lesions in contralateral thyroidian lobe after completion thyroidectomy for malignant lesions in the ipsilateral lobe, in order to establish which patients have indication of total thyroidectomy. MATERIAL AND METHOD: There were studied retrospectively 228 patients which had completion thyroidectomy after histological confirmation of the thyroid cancer in the ipsilateral lobe. RESULTS: Thyroid cancer in contralateral lobe was found in 94(41.2%) patients. One (4.7%) of patients with cancer < 1 cm in ipsilateral lob had malignant lesions in the contralateral lobe. In patients with ipsilateral lobe cancer > 1 cm, the frequency of malignant lesions was between 42.8% and 47.6%. CONCLUSION: The very high frequency of malignant lesions in the patients with ipsilateral thyroid cancer > 1 cm impose total thyroidectomy in these cases. PMID- 22308915 TI - Why do we use drains in some inguinal hernia repairs? AB - BACKGROUND AND AIMS: There is no consensus among surgeons on the indication of putting drains for in groin hernias. In this study we aimed to investigate the factors that are associated with drain usage by comparing the clinical characteristics of patients who had drains with the patients without drains in the repair of groin hernias. MATERIAL AND METHODS: The data of all groin hernia repairs from January 2006 till February 2010 in Ankara Diskapi Research Hospital were collected prospectively. The type of presentation, age, gender, presence of coexisting diseases, type of hernia, American Society of Anesthesiologists (ASA) class, type of anesthesia, postoperative general complications, local wound complications, duration of operation, and length of hospitalization, recurrence and mortality were compared between the groups of patients with drains versus without drains. RESULTS: The drains were used in 66 (8.3%) of 795 open mesh repairs of inguinal hernias. The patients who had drains were older, had cardiovascular disease, higher ASA class, received anticoagulant regimens more often, had indirect type hernia more often, more recurrent hernias, more commonly had emergency operations, had complicated presentations such as incarceration and strangulation, therefore had resections more often, pulmonary complications, had local complications such as hematoma, had longer duration of the operations and stayed longer in the hospital when compared with the patients without drains (p < 0.05). Anticoagulant use, duration of the operation, recurrent hernias and ASA class were statistically significant independent variables predicting drain use in inguinal hernias (p < 0.05). When femoral hernia repairs (n = 35) were analysed; drains were associated with male gender and long operation time (p < 0.05). CONCLUSIONS: Drains are more commonly used in patients on anticoagulants, who had long duration of the operation, recurrent hernias and high ASA class. Drain use in selected patients seems to not increase infection risk but are associated with longer hospital stay. PMID- 22308916 TI - [Immunohistochemical screening of hMLH1 and hMSH2 gene mutations in patients diagnosed with colorectal cancer and microsatellite instability suspicion]. AB - STUDY AIM: Immunohistochemical screening of hMLH1 and hMSH2 gene mutations in patients diagnosed with colorectal cancers, suspected of having microsatellite instability, as diagnosed between January 2002 and December 2009 in the Surgery Department of the CF Clinical Hospital Cluj-Napoca (prospective non-randomised study). METHODS: Inclusion criteria were adenocarcinoma pathology finding and also minimum one of the revised Bethesda criteria for genetic testing of microsatellite instability in colorectal cancers. 110 eligible patients were divided in 2 study groups according to the number of Bethesda criteria met (group A - 1 criteria; group B - 2 or more criteria). Both groups were statistically compared considering the clinical and pathological parameters specific to the Lynch syndrome. We performed immunohistochemical staining to determine the expression of hMLH1 and hMSH2 genes in the tumors of all the patients. RESULTS: We found the differences in age, colorectal family history and right colon tumor site between the two groups to be statistically significant. Immunohistochemical stainings showed lack of hMLH1 gene expresion in 9 patients and of hMSH2 gene in 4 patients respectively. CONCLUSIONS: Immunohistochemical staining can identify patients who need to be genetically tested for mutations of the DNA mismatch repair genes, in order to establish the correct diagnostic of Lynch syndrome. PMID- 22308917 TI - [Comparative study of three series of neuro-cutaneous flaps used for coverage of leg defects]. AB - The purpose of the trial was to compare three groups of neurocutaneous flaps used to cover defects in the calf, in terms of preoperative characteristics and postoperative results. The main objective was to evaluate the effectiveness of surgical method by testing the hypothesis: neurocutaneous flaps can be applied with clinical results comparable to other surgical methods. The results were presented in the text, through graphic figures and tables. Statistical comparisons were performed according to the results obtained from three series of neurocutaneous flaps in terms of demographic characteristics and those describing postoperative results. The results obtained in the three types of flaps were compared with studies published by other authors, confirming the working hypothesis. The most important results are: the neurocutaneous sural flap is a distal pedicled flap with increased vascular resistance; age and co-morbidities may influence the degree of immediate complications but not the final success rate; the covered defect surface (p = 0.035) is higher for the sural and saphenous flap; the number of days of hospitalization is significantly lower than for microsurgical transfer flaps (p = 0.022). The frequency of complications and reintervention rates were similar (p = 0.022). The study concludes that the sural neurocutaneous flap can be used to cover defects of up to 200 cm2 in the calf with similar results to those of microsurgical transfer flaps. PMID- 22308918 TI - Tissue transplantation in face reconstruction. AB - INTRODUCTION: At face level, tissue transplantation is one of the main methods in reconstructive surgery, generally used when local and locoregional reserves are outworked. To reconstruct different face units after trauma or oncologic resection we use different methods, according to dimensions, nature and site of the defect. In cases with extensive defects or mutilating sequelas, face transplantation can be a reconstructive option that should be taken in account, despite its desavantages. MATERIAL AND METHOD: In this paper we present a retrospective study of the cases we operated during 2004-2010, in our Plastic and Reconstructive Surgery Clinic of Clinical Emergency Hospital "Bagdasar-Arseni" which needed reconstructions with different tissue transplantation methods. RESULTS: Case evaluation showed that postoperative results were good and very good. For this evaluation, we took in account both case gravity and operative risks, for each reconstructive method. CONCLUSIONS: Tissue transplantation for face reconstruction represents the latest milestone in face reconstruction, as well as a preliminary stage for face transplantation, when there is right indication. PMID- 22308919 TI - [The advantages of implementing an e-learning platform for laparoscopic liver surgery]. AB - The rapid expansion of laparoscopic surgery has led to the development of training methods for acquiring technical skills. The importance and complexity of laparoscopic liver surgery are arguments for developing a new integrated system of teaching, learning and evaluation, based on modern educational principles, on flexibility allowing wide accessibility among surgeons. This paper presents the development of e-learning platform designed for training in laparoscopic liver surgery and pre-planning of the operation in a virtual environment. E-learning platform makes it possible to simulate laparoscopic liver surgery remotely via internet connection. The addressability of this e-learning platform is large, being represented by young surgeons who are mainly preoccupied by laparoscopic liver surgery, as well as experienced surgeons interested in obtaining a competence in the hepatic minimally invasive surgery. PMID- 22308920 TI - [Surgical treatment by enucleation of giant cavernous hemangiomas of the liver]. PMID- 22308921 TI - [Results of 250 gastric resections for gastric and duodenal ulcers. 1929]. PMID- 22308922 TI - [Pancreaticoduodenectomy in surgical treatment of malignant tumors of Vater's region]. AB - BACKGROUND: The optimal treatment of tumors of Vater's region represents a permanent interest of every physician involved in the treating of malignant diseases with such localization. AIM: This presentation proposes a pancreaticoduodenectomy (DPC) evaluation in the surgical treatment of tumors of Vater's ampulla. MATERIALS AND METHODS: Between 1999 - 2009 our clinic has treated a number of 37 cases with mechanic jaundice by malignant diseases (JMN). Out of these, 5 cases (13.5%) have been hospitalized with JMN (preoperative diagnose) by malignant tumors of Vater' region: 4 men and a woman, aged 46 to 72, from rural medium, who represent the aim of this paper. RESULTS. DISCUSSION: In 4 cases (10,.8%), intra-operatory exploration confirms the existence of tumors of Vater's ampulla or duodenal papilla (diagnosis having been established by preoperatory duodenoscopy) using DPC (Child Procedure). Postoperative evolution, either immediate or distanced, was favorable, implying no deaths. The microscopic exam of the extirpated piece confirms Vater's Ampulloma in two cases (5.4%); in the other two cases, the above mentioned exam reveals the small bowel's carcinoma at duodenal papilla. In the last 2.7% cases intra-operatory lymph node and visceral metastases have been observed, choledochoscopy revealing cholangiocarcinoma (confirmed by microscopic exam), the patient having suffered only a choledochoduodenostomy. CONCLUSIONS: Without being endowed with great experience in the field, the results of DPC treatment in these first cases of malignant tumors of Vater's region allow us to found the reasoning of the righteousness of surgical indication. DPC draws the hope of radical healing intention in the cancer with this localization. PMID- 22308923 TI - [Ascending colon perforation by ingested fruit stones]. AB - BACKGROUND: Ingested foreign bodies present problems due to the related complications, perforation being the most frequent. MATERIAL AND METHOD: This is a descriptive study of two cases of ascending colon perforation by numerous ingested fruit stones. The main symptoms were abdominal pain with tenderness in the lower right quadrant. RESULTS: In both cases the diagnosis was made at operation, with right hemicolectomy and termino-lateral ileo-colic anastomosis. Post-operative outcome was uneventful with the exception of a wound infection. The possible mechanism of the delayed perforation is discussed. Diagnosis and treatment modality alternatives in foreign body ingestion and the literature data are reviewed. CONCLUSIONS: Delayed perforations by ingested fruit stones can be difficult to diagnose preoperatively but if operated in due time are curable by resection of the affected bowel. PMID- 22308924 TI - [Clinical and therapeutic considerations on a case of benign phyllodes tumor]. AB - Mamary phillodes tumours represent a fairly rare pathology. They can be benign, with a high risk of getting malignant (border line) or already malignant. More than 50% of phillodes tumours are benign and usually appear with women around 45 years old. We present this case for some particular features, with both elements, of either benign or malignant. The course is totally different in the two cases, which raised the issue of the treatment options. This is the case of a 57 years old female patient, who had been admitted with a right mammary tumour, of approximatly 40/50 mm that occupied the lower breast quadrants, with irregular outline, and with necrosis and hemorrhaging zones, mobile on the thorax wall, with right axillary adenopathy, in the latero-thorax group, of 1/2 cm wide, mobile and with a non-tumour aspect. The tumour appeared 1-2 years before and developped very much in the last 2 months when necrosis zones appeared; 3-4 days before presentation to the doctor and bleeding occurred. Intraoperatively, the tumour was fix compared with the back plan, with axillary ganglions being conglomerated, being almost invasive, thus suggesting neoplastic infiltration. The postoperatory histopathological exam with parafine preparation, highlighted the presence of an adenomixofibrom, with parcelled necrosis zones, with inflamatory infiltrate. The harvested biopsies from the axillary ganglions have highlighted a companion adenopathy with inflamatory character. PMID- 22308925 TI - Isolated splenic metastasis of endometrial adenocarcinoma--a case report. AB - The spleen in rarely the place for solid, non-haematological tumors, isolated splenic metastases from adenocarcinomas being extremely rare findings, regardless of the origin and the histological type of the primary tumor. We present the case of a female patient with isolated splenic metastasis diagnosed by abdominal computer tomography at only 20 months after curative surgery for endometrial adenocarcinoma, in which the final diagnosis has been established by histological and immunohistochemical examination of the splenectomy piece. The haematogenous dissemination of the endometrial cancer occurs most commonly in the lungs, liver or bones, the spleen being rarely affected. In the medical literature there are cited up to date only 12 cases of solitary splenic metastasis from endometrial adenocarcinoma. The particularity of the case presented by us is the early appearance of an isolated splenic metastasis, at less than two years after curative surgery (compared to an average of 4-5 years cited in the literature), from an endometrial cancer which was classified histologicaly in the group with low-risk for relapse (well differentiated endometrioid adenocarcinoma). In conclusion, although solitary splenic secondary determinations are very rare, the incidence of the reported cases in the medical literature is increasing, their late appearance (a few years after the primary tumor's resection) and the lack of symptoms until the tumor reaches appreciable size or it complicates with necrosis, justifies the periodic abdominal imaging examination, on long-term, for postoperative monitorisation after the initial curative surgery. Their treatment of choice is open, classical splenectomy that must be followed by chemotherapy in order to prevent the development of other possible micrometastases. PMID- 22308926 TI - [Letter to the Romanian surgeons, members of the Romanian Surgical Society ]. PMID- 22308927 TI - Taking the long view on physician assistants. PMID- 22308928 TI - Physician assistants as servant leaders: meeting the needs of the underserved. AB - PURPOSE: The purpose of this study was to determine if the level of servant leader characteristics in clinically practicing physician assistants (PAs) in underserved populations differed from PAs serving in other locales. METHODS: Five subscales of servant leadership: altruistic calling, emotional healing, wisdom, persuasive mapping, and organizational stewardship, were measured in a quantitative study of clinically practicing PAs using a self-rating survey and a similar survey by others rating the PA. RESULTS: Of 777 PAs invited, 321 completed the survey. On a scale of 1 to 5, mean PA self-ratings ranged from 3.52 (persuasive mapping) to 4.05 (wisdom). Other raters' scores paired with the self rated PA scores were comparable in all subscales except wisdom, which was rated higher by the other raters (4.32 by other raters, 4.01 by PAs, P= .002). There was no significant difference in the measures of servant leadership reported by PAs serving the underserved compared to PAs serving in other populations. Servant leader subscales were higher for PAs compared to previous studies of other health care or community leader populations. CONCLUSION: The results found that the PA population studied had a prominent level of servant leadership characteristics that did not differ between those working with underserved and nonunderserved populations. PMID- 22308929 TI - The use of prescription stimulants to enhance academic performance among college students in health care programs. AB - PURPOSE: Prescription stimulant use as academic performance enhancers is increasingly widespread among college students. The purpose of this study was to evaluate the prevalence of prescription stimulant use among health care students attending a university in the northeastern United States. The study investigated the specific stimulants being used and the frequency of usage. It also examined the rates of nicotine, alcohol, and drug abuse versus dependence. METHODS: A web based survey was administered to medical and health profession students regarding prescription stimulant use for nonprescribed purposes. Tobacco, alcohol, and recreational drug use were also surveyed. RESULTS: Approximately 10.4% (32) of students surveyed have either used a stimulant or are currently using prescription stimulants illegally. The most common reason for stimulant use was to focus and concentrate during studying (93.5%). Of the 308 students, 45.2% were female, 83.9% were Caucasian, and amphetamine-dextroamphetamine was the most commonly abused stimulant (71.4%). CONCLUSIONS: Results from this study are consistent with previous research of undergraduate students regarding prescription stimulant use for nonprescribed purposes, specifically for academic performance enhancement. Data from the study support that alcohol abuse and dependence among students is a pertinent concern, suggesting that substance abuse in general must be addressed. Substance abuse and awareness programs combined with stress management programs in an overall substance-abuse reduction strategy, including the use of prescription stimulant use beyond the originally intended purpose, may be beneficial. Because of the lack of research focusing on graduate health care students, further investigations should use similar populations. PMID- 22308930 TI - Physician assistant self-assessment of entry-level competency: A comparison with observations of supervising physicians. AB - PURPOSE: The present study was conducted to gain comparative knowledge of physician assistants' and supervising physicians' perceptions of adequacy of physician assistant (PA) preparation at entry-level for effective practice in the primary care setting. METHODS: The sample included 1,000 PAs working in their first professional employment and their supervising physicians. Each PA/physician pair independently completed a survey to evaluate knowledge, skills, and patient care as well as diagnosis, management, and treatment of common conditions encountered in primary care. A 3-point scale for Entry-Level and Required Knowledge and Skills was used to assess proficiency: (1) exposed to subject area, but lack confidence in knowledge and/or practice skills; (2) have general knowledge and understanding of subject area and believe prepared for entry-level practice; and (3) have thorough knowledge of subject matter and expertise in practice. Competence was defined at 2.0. RESULTS: Ten percent (n = 98) of PAs and 5% (n = 46) of physicians responded to the survey. PA means were below 2.0 in 13 of 31 medical knowledge and patient care competencies and four of five medical/surgical procedures evaluated. With regard to diagnosis, management, and treatment of common medical conditions, the PA ranking was > 2.0 in 17 of 18 competencies. Overall, physicians' ranking of PA preparations were higher than PA self-assessments, reaching significance in 13 of the 54 competencies. CONCLUSIONS: While PAs were less confident and competent regarding entry-level medical knowledge and patient care, self-reported ability to diagnose, manage, and treat common conditions was ranked as competent for their current practice setting and met expectations of supervising physicians. PMID- 22308931 TI - The evaluation of physician assistant students' history-taking abilities using actors as standardized patients. AB - PURPOSE: The value of professional actors as standardized patients (SPs) was evaluated in an exercise that normally uses students for SPs. METHODS: A history taking instructional curriculum was developed for a clinical skills exam for second-year students. Students anonymously rated their impressions of actors versus physician assistant (PA) students as patient simulators and assessed this exercise in the terms of the history-taking task areas described in the National Commission on Certification of Physician Assistants (NCCPA) Blueprint. RESULTS: PA students perceived the actor SPs as more similar to real patients than peers simulating patients, developed greater confidence in history-taking ability, and believed that they significantly enhanced their history-taking skills. CONCLUSIONS: This study demonstrates that students value the use of professional actors to simulate patients in teaching history-taking. Overall positive results encourage the use of professional actors as standardized patients. PMID- 22308932 TI - Exploring the theoretical framework of cultural competency training. AB - Cultural competency has become an important component of physician assistant education. How to implement the cultural competency training is still daunting to many PA educators. Theoretical frameworks of cultural competency training emphasize moving from exposure to diversity and fostering cultural awareness, to obtaining cultural knowledge and cultural skills, and then applying the knowledge and skills to actual diverse patient populations. Only by moving through the phases of the theoretical frameworks will students sincerely understand culture and the importance of cultural competency training in decreasing health care disparity. PMID- 22308933 TI - In full bloom: helping students grow using the taxonomy of educational objectives. PMID- 22308934 TI - A student's international research project on best practices used by Peruvian maternal health care providers. PMID- 22308935 TI - The impact of social media and technology on professionalism in medical education. AB - The use of social media is the norm among the digital native generation, with 75% of the Millennial Generation connected through Facebook. For students in medical education who struggle to distinguish between personal and professional boundaries, social media provides yet another challenge. Incidents of unprofessional conduct and academic dismissal have been reported. Administration, faculty, and students would benefit from clear policies and procedures, case scenarios of social media violations, and suggestions for using social media wisely. PMID- 22308936 TI - [Global strategies to reduce salt intake]. AB - Currently, cardiovascular diseases (CVD) are the leading cause of death worldwide. High blood pressure is one of the main risk factors for the development of CVD and blood pressure levels are strongly associated with salt intake. Worldwide, salt consumptions accounts more than two fold the recommended daily intake, which has been described to be associated with CVD and some cancers. Benefits of decrease salt intake (reduction of morbidity, mortality and health related costs) have promoted several public health strategies to reduce salt consumption globally. Among the most commonly used strategies include educational campaigns and the gradual decrease of added salt in processed foods. Chile has joined these initiatives with an agreement between the producers of bread and the Ministry of Health to gradually decrease the concentration of salt in bread nationwide. The purpose of this review is to provide updated information regarding recommended intakes of salt, real intake, adverse effects of excess consumption, profits attributable to a decline and analyze the global strategies to reduce salt intake in the population. PMID- 22308937 TI - [New classification of causes of mortality of nutritional origin by means of the Delphi method]. AB - The causes of mortality of nutritional origin (MNO) are not classified in the consecutive reviews of the international disease classification (IDC) and there is no agreement for their most proper classification. The objective of this study is to elaborate, using the last ICD as a guide, a list of causes of mortality of nutritional origin which will be used as a reference in future studies. A two round Delphi method was organized with an expert's consenssus in clinical nutrition. The experts were asked to classify a list of causes of MNO in 4 groups; 1) group A: congenital errors related to nutrition, 2) group B: Causes associated with other pathologies, 3) group 3: Excess and defect nutrition disorders, and 4) excluded. In total, 86 causes of MNO were taken under the consensus of experts, and 79 (91.9%) came to an agreement. 14 (17.7%) causes were classified in group A, 5 (6.3%) causes in group B, 37 (46.8%) causes in group C and 23 (29.1%) were excluded. This is a first approach to the classification of mortality causes of nutritional origin, probably due to the ambiguity and disparity of opinions between experts with respect to these causes. This new classification will be very useful due to the fact that it will enable homogenization of the studies and that way we will have comparable studies, using it as a clarifier annex for the ICD of the moment. PMID- 22308938 TI - [Relation of total cholesterol in serum tocopherols, probabilistic study in Mexican children]. AB - Epidemiological studies have shown the effect of nutritional status of tocopherols and development of cardiovascular diseases that now are more frequent during early years of life. In this work we evaluated the association between the total cholesterol and serum levels of tocopherols in a population of Mexican children in whom we measured the oxidant status and antioxidant capacity (December 2003). In 1155 children (12-59 months) residents of urban and rural locations we quantified in serum alpha-tocopherol, gamma-tocopherol and total cholesterol; the antioxidant capacity and oxidative status were evaluated with the production of TBARS. Children with serum cholesterol < 170 mg/dL had an average of 472.5 +/- 179.6 microg/dL tocopherol in serum and > or = 240 mg/dL cholesterol recorded an average of 577.3 +/- 200.8 microg/dL. However, when tocopherols were expressed in relation to total cholesterol (micromol/mmol) found that children with < 170 mg/dL had the highest ratios (3.06 +/-1.19) which places them in an adequate nutritional status of tocopherol, unlike the group with > or = 240 mg/dL of cholesterol in whom the relationship was low (1.93 +/- 0.69). There were no differences in serum antioxidant capacity, but if in the production of TBARS for children with > or = 200 mg/dL cholesterol. In preschools the increases in total cholesterol limits the availability of serum tocopherol for circulating lipids, this condition over time could determine the early development of vascular injury mediated by oxidative stress. PMID- 22308939 TI - Heat-treated hull flour does not affect iron bioavailability in rats. AB - In this study the chemical composition and iron bioavailability of hull and hull less soybean flour from the new cultivar UFVTN 105AP was evaluated. The hemoglobin depletion-repletion method was used in Wistar rats. Soybean hull flour presented 37% more total dietary fiber and higher content of iron than hull-less soybean flour. The phytate:iron molar ratio, however, was 2-fold lower in the soybean hull flour in compared to the hull-less soybean flour. Animals fed soybean hull flour presented hemoglobin gains similar to those of the control diet group (p > 0.05). The Relative Biological Values of hull and hull-less soybean flour were 68.5% and 67.1%, respectively, compared to the control group. Heat-treated soybean hull flour (150 degrees C/30 minutes) showed high content of iron and low phytate, which favors the iron bioavailability. Thus, the soybean hull flour is a better source of dietary fiber and iron than hull-less soybean flour at comparable bioavailabilities. PMID- 22308940 TI - [Comparative study of the consumption of virgin olive oil or seje on lipid profile and oxidation resistance of high density lipoprotein (HDL) of rat plasma]. AB - We compared the effect of the consumption of seje oil (Oenocarpus bataua), with that of olive oil, on plasma lipids and susceptibility in vitro to oxidation of high density lipoprotein (HDL) in the rat. Two groups often male Sprague Dawley rats were fed ad libitum, for a lapse of eight week, with a purified diets with 10g de seje oil or olive oil/100 g of diet (GS y GO respectively). The animals were exsanguinated at the end of the experimental after a 14 hour fast. Plasma was isolated by centrifugation, and the fractions of lipoproteins were separated from the plasma by sequential ultracentrifugation. Rats of GO had a statistically significant lower in concentration of TG (p < 0.05) compared with GS group. HDL fractions in both groups were oxidatively modified by incubation with copper ions. Differences in the fractions susceptibilities to peroxidation were studied by measuring the formation of thiobarbituric acid reactive substance (TBARS) for 3 hours. HDL in GS had a statistically significant decrease in TBARS formation (p < 0.05) relative to HDL of GO. This may be explained by the lower concentration of polyunsaturated fatty acids of HDL in GS compared with HDL in GO. PMID- 22308941 TI - Increase of plasma fatty acids without changes in n-6/n-3-PUFA ratio in asymptomatic obese subjects. AB - Obesity is associated with a low grade inflammation which contributes to the development of insulin resistance and diabetes. The aim of this study was to assess the total saturated (SFAs), monounsaturated (MUFAs) and polyunsaturated fatty acids (PUFAs) in plasma from asymptomatic obese subjects and to determine the arachidonic/eicosapentanoic acid ratio [ARA/EPA] as a marker of inflammation, and its eventual association with ultrasensitive CRP. Fourteen obese (34.4 +/- 11.1y.; BMI: 36.0 +/- 4,5 kg/m2) and 12 normal-weight (30.6 +/- 7.8y.; BMI: 23,6 +/- 2,4 kg/m2) subjects were recruited and their plasma fatty acids were determined by gas chromatography. usCRP was higher in the obese subjects (p = 0.01) and correlates with their body fat content. The percentages of SFAs, MUFAs, PUFAs were not affected in the obese subjects but their concentrations were increased, compared with the control group. However, no differences in the long chain PUFAs (DHA and EPA) concentrations or in the plasmatic ARA/EPA ratio were observed in these subjects. These observations do not support a relation between the ARA/EPA ratio and the presence of low grade inflammation evaluated by plasma usCRP in this group of asymptomatic obese subjects. PMID- 22308942 TI - [Barriers and facilitators to increase consumption of fruits and vegetables in six countries in Latin America]. AB - Low intake of fruits and vegetables is among the risk factors for cardiovascular disease and some cancers. The countries have implemented policies to promote food consumption. Identifying the barriers perceived by people to consume it helps to recognize the resources that would be willing to exchange for benefits. The objectives of this study are to determine what factors are facilitators and barriers to increasing consumption of fruits and vegetables in six countries in Latin America, and a possible relationship between the 5 a day program and the food based dietary guidelines. This is a qualitative and field study. Techniques used were group interviews with health professionals and the media, and interviews with experts in food policy. The outstanding facilitators were television advertising campaigns promoting their use, and the existence of fruits and vegetables markets in the neighborhoods. Highlighted those obstacles were lack of public policies of advertising regulations and trade hooks of food, of self-sustainability, of funding for related programs, and of sociological research of the topic. The main barrier to the consumption of fruits and vegetables in these countries was the lack of policy support and related public policy, being a good advertising campaign vital to the success of programs that encourage consumption. The main relationship between the Dietary Guidelines and the 5 A Day Program is to both promote the consumption of vegetables and fruits. PMID- 22308943 TI - [Food promotion and food preferences in Chilean school age children from different socioeconomic levels]. AB - To determine the attitude towards marketing of food and beverages a sample of 1,048 school children ages 8 to 13 from three cities of Chile (north, center and south of the country) were interviewed. The instrument applied was a validated questionnaire used in previous studies. A descriptive analysis of the variables was performed and differences were determined by region, socioeconomic level (SEL) and gender using Chi2 test. Differences per SEL were higher in Santiago. A greater proportion of school children of medium-low SEL watched more than 2 hours of TV during weekdays and weekends (p < 0.001). The proportion of children that liked food and beverage commercials was greater in medium-low SEL in Santiago (66%) (p < 0.001), as opposed to 26 to 35% in the medium high SEL. A high percentage indicated that they liked promotional campaigns of foods at supermarkets, on the streets, shopping centers and on the Internet. The preferred commercials were those for beverages, chocolates, ice-creams and cereals. Most common foods taken from home to school were cookies, fruits and yogurt. Most of the children had money available to buy food and the products more frequently preferred were cookies, sweets, French fries, beverages with sugar, chocolates, ice-creams and hot-dogs. CONCLUSION: marketing of food and beverages is recognized and remembered by school age children, influencing what they buy and consume regularly at school. PMID- 22308944 TI - [Food satisfaction in Mapuche persons in the Metropolitan Region of Santiago, Chile]. AB - Although the study and measurement of satisfaction with life has generated great interest in the last 15 years, there are few works which address satisfaction with food-related life. In order to identify variables which have an influence on satisfaction with food-related life among Mapuche persons, a survey was applied to 400 Mapuche subjects in the Santiago Metropolitan Region, Chile. The scales evaluated in the questionnaire included: SWFL (Satisfaction with Food-related Life), lifestyles, food, and Mapuche acculturation. It was found that 41.0% were extremely satisfied, 40.5% satisfied, 17.2% somewhat satisfied and 1.2% dissatisfied with their food-related life. To identify variables which have an influence on satisfaction with food, an ordinal multinomial logit model was proposed, which was significant (p < 0.01) as a whole. The probability of high satisfaction with food-related life increases as there are fewer children in the household, the person's expenditure on food increases, the person consumes some Mapuche foods, is aged 55 or more, consumes red meat in moderation, consumes foods without additives, try to balance work and private life, does not read the labels of products, and if he/she had Mapuche friends at school. Thus satisfaction with food-related life in Mapuche persons in the Metropolitan Region is related to demographic variables, expenditure on food, consumption of Mapuche foods and life-style. PMID- 22308945 TI - [Microbiological stability through storage period of Sphyraena ensis in Costa Rica]. AB - At the present study some of the microbiological and biochemical changes that occur through storage period in Sphyraena ensis, a fish specie of frequent consumption in Costa Rica were studied. Samples of S. ensis obtained during rainy and dry season were evaluated. Analysis included aerobic psychrotrophic count, identification and count of Vibrio, Enterococcus and Pseudomonas through a six day storage period at two different refrigeration temperatures, 2 and 7 degrees C. Same time, a commercial enzymatic immunoassay was used for the evaluation of the variation on the concentration of histamine produced in the different samples. Results obtained show that there is an increase on the bacteriological counts through the storage period, this increase is bigger as refrigeration temperature increases. Most of the samples maintained at 7 degrees C showed counts above 106 CFU/g after three days of storage, those stored at 2 degrees C did not present such high population levels. Nevertheless, after 6 days of storage, all samples, despite the storage temperature used, presented levels above the described one. Also, an histamine concentration increased through storage time, especially when the product was conserved at the higher temperature due to an increase in the number of histidine descarboxilating bacteria. There is no statistical difference between the counts obtained during rainy or dry season; nevertheless, there is a difference assicieated to the bacterial genera isolated. PMID- 22308946 TI - [Assessment of dairy products quality by means of electronic nose]. AB - The electronic nose, instrument that uses a group of sensors and a system of pattern recognition for the qualitative analysis of aroma, has found many applications in the food industry, because of its versatility. In this work a brief description of the electronic nose, its operation mode and its advantages and disadvantages were carried out. Moreover, the main applications of this instrument in the food industry, with special emphasis on the dairy industry, have been reviewed. These applications include the detection of microorganisms in milk, the identification of off-flavours in milk, the shelf life of milk and various types ofcheeses, the identification of mastitic milk, the classification of cheeses according to their time of ripening, the discrimination of cheeses by geographic origin and the control of the milk fermentation, among other. The results of this review indicate that electronic nose could be used as an instrument for the rapid quality control of dairy products. PMID- 22308947 TI - [Biochemical, physicochemical and functional characterization of turbot (Scophthalmus maximus). Study of the changes occurring during the 4 degrees C storage]. AB - The turbot (Scophthalmus maximus) is a kind of flatfish that is well adapted to intensive farm culture. After the harvest it is necessary to know the physicochemical, biochemical and technological properties and if during the refrigerated storage, changes of these properties are developed. The main objective of the study was the assessment of the proximal composition, the biochemical, physicochemical and functional properties, and how they are influenced during the 16 days storage at 4 degrees C. Parameters such as centesimal composition, PAGE-SDS, and protein thermal stability through a DSC were carried out. pH, total volatile base-nitrogen (TVB-N) dripping, texture, holding water capacity (WHC), emulsification (EC) and gelification (GC) were also determined. Results for the proximal composition were: humidity 76.3%; fat content 2.71%; proteins 19.6%; and ashes 1.3%. Two different thermal transitions at 47.5 degrees C (myosin) and 76.9 degrees C (actin) were observed. The PAGE-SDS showed profiles corresponding to myofibrilars and sarcoplasmatic proteins, which presented no changes during the storage. pH experimented an increase from 5.9 to 6.6; TVB-N showed a variation from 20.0 to 39.5 mg TVB-N/100 g of muscle at the day 16. The WHC started with a 10.5% and ended in 58.1%; no GC was observed. The increase of the EC and WHC during the storage was due to conformational changes of proteins. The compression force presented a fluctuation between 111.2 and 106.0 N and the shear strain decreased during the storage from 148.6 to 95.2 N. The dripping showed a variation between 1.7% and 2.5%. According to the results of the storage during 16 days at 4 degrees C, the NBV-T content determined a shelf life of 14 days. PMID- 22308948 TI - [Development of mixed beverages made of caja (Spondias mombin L.) and cashew apple (Anacardium occidentale) added of fructooligosaccharides and inulin]. AB - The purpose of this work was to develop three mixed drinks based on caja (Spondias mombin L.) and cashew apple (Anacardium occidentale) pulps, added prebiotic ingredients and to evaluate their chemical, physicochemical and sensory properties. Four formulations with combinations of two pulp fruit, sucrose and prebiotic ingredients (Standard inulin, inulin high performance-HP-and fructooligosaccharides FOS) were developed. The mixed drinks were submitted the following analysis pH, acidity, soluble solids, sugars, ascorbic acid, total carotenoids, total polyphenols and acceptance ratings of the sensory attributes such as: consistency, sweetness and overall impression, attitude and consumers purchase preference. The pH, total soluble solids and polyphenol results showed difference (p < or = 0.01) significant, while for the analysis of total acidity, sugars, ascorbic acid and carotenoids, it was not observed significant difference. The sensory attributes evaluates showed results ranging in scale between "I did not like or disliked "and" liked "(average 5.80 to 7.06). The attributes sweetness, consistency and attitude of buying showed no difference (p > 0.05) between drinks, however, differed significantly (p < or = 0.05) for the attribute of overall impression. The drink with FOS showed a similar acceptance when compared to traditional (sucrose) drink, showing an option of meeting the functional food expectations of consumers, who seek healthy, nutritious and tasty foods. PMID- 22308949 TI - [Development of cereal bar with pineapple skin]. AB - The cereal bars are multi-component products consisting of cereals, dried fruit and syrup binder and may be added to the consumable parts of fruits and vegetables which usually are not exploited and have high nutritional value, thereby reducing food waste. It was developed a jam with pineapple skin, which it was utilized in 13.5% in the cereal bar formulation. The cereal bar was sensorial evaluated and had its centesimal and mineral composition determined. The new product achieved average of 8.3 for global impression using 9 points hedonic scale, 91% of acceptance rate and 67% of purchase intent. In this first use of pineapple skin jam as food ingredient it can be concluded that its aggregation in the cereal bar formula is feasible, making an accepted product with fibers, proteins and minerals, as an alternative to traditional cereal bars. PMID- 22308950 TI - [The objective assessment of the quality of oral health care and development of quality indicators]. AB - Public health care administration and decision-makers need appropriate tools and information to assess and monitor oral health needs and improve the performance of the oral health system. The aim of the article is to introduce the available methods of measurement of the quality of service, to give a brief summary considering the role of quality indicators in domestic and international sources and the European indicator project (EGOHID) and to introduce ICDAS (International Caries Detection and Assessment System), the method used for clinical examinations. The clinical indicators - that are produced from data gained from the questionnaires and screenings--provide an opportunity to improve and develop quality. Quality indicators are objective measure of the process or outcome of patient care. The 40 indicators were created by the experts of EGOHID program which are described in four categories. Part A is indicators for monitoring the oral health of children and adolescents, Part B is in general population, Part C is indicators for monitoring the oral health systems, Part D concerns indicators for monitoring the oral health quality of life. The purpose of developing public health care and--within it--dental care is the effective use of resources and besides it, reaching the popular level of health gain for which it is a necessary tool when forming and continuously developing the quality approach of providers. PMID- 22308951 TI - [Pain and discomfort in orthodontic treatments. Literature review]. AB - The experience of pain and discomfort during orthodontic treatment is common. Pain is a subjective response to noxious stimuli, but it is also influenced by age, gender, previous pain experience, emotional factors and stress. The ortodontic treatments such as separation, placement of the arch wire, activation of the fix or removable appliances and debonding cause some degree of pain for the patient. In a prospective study 95% of the patients reported pain experience during orthodontic treatment. The periodontal pain caused by the combination of pressure, ischemia, inflammation and oedema. The pain starts within 4 hours, increases over the next 24 hours, and decrease within 7 days, so it may not be identified by the orthodontist at recall visit. The most common method to measure the intensity of the pain is the NRS (numerical rating scale), where patients can rate their pain intensity from 1 to 10 or 1 to 100. There are many modalities to control orthodontic pain, we can use different analgesic agents, solf-laser irradiation, transcutaneous electrical nerve stimulation and hypnotherapy. The aim of this review to provide an overview on discomfort and pain reaction during orthodontic treatments and discussion of the possible measurement and alleviation of pain. PMID- 22308952 TI - [Commemoration. In honour of Gyorgy Huszar (1911-2002) and Bela Berenyi (1911 2005) -- on the centenary of their births]. AB - 100 years ago two outstanding teachers of the Faculty of Dentistry of the Semmelweis University (Budapest) were born. Dr. Huszar was a prosthodontist, an expert on metal and other dental materials, as well as a geroprosthodontist and medical historian. Professor Berenyi was internationally recognized as an expert on salivary gland surgery and also orthognatic surgery. Both of them published several textbooks and many hundreds of scientific papers in Hungarian and in foreign languages. They were internationally recognized scientists, members of several national and international societies, as well as editors of national and international dental journals. PMID- 22308953 TI - [Control of generalized chronic periodontitis combined with calcium-antagonist related gingival overgrowth by a complex periodontal-endodontic-prosthodontic treatment. Case report]. AB - To day a relatively high percentage of elderly population of the industrialized world suffers with different cardiovascular diseases and are on permanent antihypertensive therapy. One of the most frequently used drugs is the calcium channel blockers prescribed against high blood pressure. The most common oral side effect of these drugs is the gingival enlargement that might develop even on otherwise healthy gingiva. The incidence of chronic periodontitis in this age group is also high and the Ca antagonist medication in those individuals might substantially modify the clinical course of periodontal inflammation leading to gingival enlargement and hypertrophic pocket wall. The case presented here is a 52 years old hypertonic woman with a long history of Ca-antagonist therapy and generalized chronic periodontitis combined with gingival hyperplasia. After the change of medication the 1,5 years comprehensive periodontal endodontic and prosthodontic therapy restored patient's periodontal health and provided complex dental rehabilitation. Nevertheless, only regular periodontal supportive therapy could ensure predictable outcome and guarantee long lasting periodontal health. PMID- 22308954 TI - [Retention and relapse. Review of the literature]. AB - The retention after orthodontic intervention is just as important part of the therapy as the activ treatment. It is difficult to find statistical data about the frequency and the average degree of the relapse, but some restitution in lower denture is observable in the 70-90% of the cases, in the postretention period. The upper jaw is also frequently touched, but the prevalence and the rate is milder. The authors of this article tried to collect all the factors which are responsible for the orthodontic relapse and to determine the rules should be kept by the planning and the management of the therapy. The age and the maturity of the patients, the result of the orthodontic intervention, the origin and the character of the anomaly, the type of the retainer, the compliance of the patients; all can influence the chance of the relapse. There are some anomalies which more frequently relapse, contrarily some orthodontic irregularities have quite good long-term prognosis. In the first 6 month after the orthodontic treatment any kind of retainer has to be worn nearly 24 hours/day, later 12-14 hours daily wear seems to be satisfactory. The retention period should be twice longer than the activ orthodontic treatment, posteriorly the appliance can be left gradually. Certainly the length of the retention depends on compliance of the patients. Among the retention appliances the fixed retainers are suggested in the lower front area, because the lower incisors are most frequently relapsed. PMID- 22308955 TI - The role of transient receptor potential channel blockers in human gastric cancer cell viability. AB - Transient receptor potential cation channel, subfamily M, receptor 7 (TRPM7) is a ubiquitous divalent-selective ion channel with its own kinase domain. Human gastric cancer cells express the TRPM7 channel, and the presence of this channel is essential for cell survival. Recent studies have suggested that 5-lipoxygenase (5-LOX) inhibitors are potent blockers of the TRPM7 channels. The aim of this study was to show the effects of 5-LOX inhibitors on the growth and survival of gastric cancer cells. Among 5-LOX inhibitors, nordihydroguaiaretic acid (NDGA), 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA861), and 3 [1-(p-chlorobenzyl)-5-(isopropyl)-3-tert-butylthioindol-2-yl]-2,2 dimethylpropanoic acid (MK886) were potent blockers of TRPM7-like currents in gastric cancer cells and also induced cell death. However, zileuton was ineffective in suppressing TRPM7-like current activity and inducing cell death. Moreover, a specific transient receptor potential cation channel, subfamily C, member 3 (TRPC3) inhibitor, a pyrazole compound (Pyr3), and a specific melastatin TRP (TRPM4) inhibitor, 9-phenanthrol, did not affect TRPM7-like currents or induce cell death. We conclude that TRPM7 has an important role in the growth and survival of gastric cancer cells and a likely potential target for the pharmacological treatment of gastric cancer. PMID- 22308957 TI - Cholesterol-induced variations in the domain structure fluctuations and microdynamics of lipid membranes. AB - Broadband ultrasonic attenuation spectra (100 kHz to 2 GHz) of aqueous solutions of vesicles from 1,2-dimyristoyl-l-3-phosphatidylcholine, with different amounts of cholesterol admixed, have been measured at temperatures between 20 and 28 degrees C. The spectra have been evaluated in terms of suitable relaxation functions. They are discussed in view of the effect of cholesterol on the membrane behavior around the gel-fluid phase transition temperature T(m). In addition to a frequency-independent asymptotic high-frequency term, all spectra reveal a critical term and a Debye-type relaxation term with relaxation time around 0.5 ns. The former is evaluated in the light of the Bhattacharjee-Ferrell dynamic scaling theory. It is assigned to the critical domain structure fluctuations of the membranes. Critical slowing of fluctuations is demonstrated. Also shown are relations of the critical amplitudes to thermodynamic parameters. The Debye term reflects the rotational isomerization of the phospholipid alkyl chains. The relaxation time of isomerization reveals a significant steplike change at T(m). At moderate cholesterol content an additional Debye relaxation term exists. It is assigned to the axial diffusion of the membrane molecules. Because it likewise shows effects of slowing near T(m), the diffusion appears to be coupled to the domain structure fluctuations. A further relaxation term at small cholesterol concentration is assumed to be due to small-range shape fluctuations of vesicles near the phase transition temperature. PMID- 22308958 TI - Photoinduced band gap shift and deep levels in luminescent carbon nanotubes. AB - Individual air-suspended single-walled carbon nanotubes are imaged both spatially and spectrally in photoluminescence. At low excitation power, photoluminescence is bright and stable with high quantum efficiency; however, higher power initially causes a gradual red shift and then more severe changes. Blinking, the loss of quantum efficiency, and the appearance of new deep levels are all seen and can be explained by the introduction of defects. We propose that optical excitation induces molecular deposition onto the nanotube by optically induced van der Waals interactions, leading to physisorption and ultimately chemisorption which severely degrades the luminescence. PMID- 22308959 TI - Metabolic syndrome: new targets for an old problem. PMID- 22308960 TI - ABAB homoleptic bis(phthalocyaninato)lutetium(III) complex: toward the real octupolar cube and giant quadratic hyperpolarizability. AB - The concept of octupolar molecules has considerably enlarged the engineering of second-order nonlinear optical materials by giving access to 2D and 3D architectures. However, if the archetype of octupolar symmetry is a cube with alternating donor and acceptor groups at the corners, no translation of this ideal structure into a real molecule has been realized to date. This may be achieved by designing a bis(phthalocyaninato)lutetium(III) double-decker complex with a crosswise ABAB phthalocyanine bearing alternating electron-donor and electron-acceptor groups. In this communication, we present the first step toward this goal with the synthesis, crystal structure determination, and measurement of the molecular first-order hyperpolarizability beta by harmonic light diffusion, of an original lutetium(III) sandwich complex displaying the required ABAB-type alternation for one face of the cube. This structure is characterized by an intense absorption in the near-IR due to an intervalence transition and exhibits the highest quadratic hyperpolarizability ever reported for an octupolar molecule, ? = 5750 * 10(-30) esu. PMID- 22308961 TI - Assessment of Toll-like receptor-4 gene polymorphism on pyelonephritis and renal scar. AB - The aim of this study was to evaluate the effect of the TLR-4 gene TLR4 c.896A < G polymorphism on the development and clinical severity of urinary tract infections (UTI) and renal scar formations in children. The patients with first diagnosis of UTI (n = 112) and healthy controls (n = 93) were enrolled in the study. The TLR4 c.896A < G polymorphism was analysed in groups. The mean age of the patients in the study group was 8.1 +/- 3.5 years and 9.2 +/- 2.7 years for those in the control group. The TLR4 c.896A < G polymorphism was detected in 12.5% in the UTI group and in 15.1% of the control group. Forty patients showed pyelonephritis (PN) with scar tissue, 37 patients had PN without scars, and 35 patients had lower UTI. The TLR4 c.896A < G polymorphism was found in 22.5% of patients with scar-positive PN, and it was also present in 10.8% of patients with scar-negative PN and 2.9% of patients with lower UTI. We found higher TLR4 c.896A < G polymorphism and allelic frequency in patients with upper UTI compared to patients with lower UTI (P = 0.041 and P = 0.039, respectively). No significant difference was observed between patients and the control group for TLR-4 c.896A3. The TLR4 c.896A < G polymorphism and alleles were higher in patients with upper UTI than in patients with lower UTI. The TLR4 c.896A < G polymorphism frequency was nearly twice that in the scar-positive PN patients when compared to the scar negative patients. Larger-scale studies involving larger numbers of patients should be performed. PMID- 22308962 TI - Thermal oxidation studies on reduced folate, L-5-methyltetrahydrofolic acid (L-5 MTHF) and strategies for stabilization using food matrices. AB - The thermal stability of L-5-methyltetrafolic acid (L-5-MTHF) was investigated in model/buffer systems and food systems. L-5-MTHF degradation followed first-order reaction kinetics with relatively greater (P < 0.01) stability at pH 4 compared to pH 6.8 in the buffer systems. This was confirmed using cyclic voltammetry. The stability (for example, k-values) of L-5-MTHF in an oxygen controlled environment improved (P < 0.001) proportionally when in the presence of increasing molar ratios of sodium ascorbate (NaAsc). The addition of NaAsc to L-5-MTHF after heat treatment was also effective at returning thermally oxidized L-5-MTHF back to its original form. A scheme was developed to explain the degradation and regeneration of L-5-MTHF. The importance of antioxidant protection of L-5-MTHF from thermal oxidation was extended using 2 distinct food systems; namely skim milk and soy milk, both with known antioxidant capacities. We conclude that the antioxidant activity of food components can enhance the stability of L-5-MTHF. PMID- 22308963 TI - Unintentional fall injuries among US children: a study based on the National Emergency Department Sample. AB - This study uses national data to describe the patterns and aetiologies for childhood falls in a high-income country, the United States. We conducted a retrospective analysis of data for children aged 0-17 years from the 2007 Nationwide Emergency Department Sample (NEDS). Sample weights provided by NEDS were used to make national estimates. We estimated that in 2007 there were more than 2.3 million paediatric fall-related emergency department (ED) visits at a rate of 3217 visits per 100,000 children. Over 95% of those seen for fall injuries were treated and released. In addition, government sources made payments for just under one-third of these visits. Of those ED visits that result in hospitalisation, we found marked age patterns in bodily location of injury. The impact of fall-related injuries on EDs in the US is substantial within the paediatric population. The use of national level ED data shows age and gender patterns in paediatric fall injury not readily apparent in previous studies. There are patterns in external cause of injury and bodily location of injury that can be used to guide age specific prevention interventions. PMID- 22308964 TI - Job engagement, job satisfaction, and contrasting associations with person-job fit. AB - Forms of well-being vary in their activation as well as valence, differing in respect of energy-related arousal in addition to whether they are negative or positive. Those differences suggest the need to refine traditional assumptions that poor person-job fit causes lower well-being. More activated forms of well being were proposed to be associated with poorer, rather than better, want-actual fit, since greater motivation raises wanted levels of job features and may thus reduce fit with actual levels. As predicted, activated well-being (illustrated by job engagement) and more quiescent well-being (here, job satisfaction) were found to be associated with poor fit in opposite directions--positively and negatively, respectively. Theories and organizational practices need to accommodate the partly contrasting implications of different forms of well-being. PMID- 22308965 TI - Work-focused treatment of common mental disorders and return to work: a comparative outcome study. AB - The aim of this study was to compare the effectiveness of two individual-level psychotherapy interventions: (a) treatment as usual consisting of cognitive behavioral therapy (CBT) and (b) work-focused CBT (W-CBT) that integrated work aspects early into the treatment. Both interventions were carried out by psychotherapists with employees on sick leave because of common mental disorders (depression, anxiety, or adjustment disorder). In a quasi-experimental design, 12 month follow-up data of 168 employees were collected. The CBT group consisted of 79 clients, the W-CBT group of 89. Outcome measures were duration until return to work (RTW), mental health problems, and costs to the employer. We found significant effects on duration until RTW in favor of the W-CBT group: full RTW occurred 65 days earlier. Partial RTW occurred 12 days earlier. A significant decrease in mental health problems was equally present in both conditions. The average financial advantage for the employer of an employee in the W-CBT group was estimated at $5,275 U.S. dollars compared with the CBT group. These results show that through focusing more and earlier on work-related aspects and RTW, functional recovery in work can be substantially speeded up within a regular psychotherapeutic setting. This result was achieved without negative side effects on psychological complaints over the course of 1 year. Integrating work-related aspects into CBT is, therefore, a fruitful approach with benefits for employees and employers alike. PMID- 22308966 TI - The buffering effect of selection, optimization, and compensation strategy use on the relationship between problem solving demands and occupational well-being: a daily diary study. AB - This study investigated within-person relationships between daily problem solving demands, selection, optimization, and compensation (SOC) strategy use, job satisfaction, and fatigue at work. Based on conservation of resources theory, it was hypothesized that high SOC strategy use boosts the positive relationship between problem solving demands and job satisfaction, and buffers the positive relationship between problem solving demands and fatigue. Using a daily diary study design, data were collected from 64 administrative employees who completed a general questionnaire and two daily online questionnaires over four work days. Multilevel analyses showed that problem solving demands were positively related to fatigue, but unrelated to job satisfaction. SOC strategy use was positively related to job satisfaction, but unrelated to fatigue. A buffering effect of high SOC strategy use on the demands-fatigue relationship was found, but no booster effect on the demands-satisfaction relationship. The results suggest that high SOC strategy use is a resource that protects employees from the negative effects of high problem solving demands. PMID- 22308967 TI - Help yourself: the mechanisms through which a self-leadership intervention influences strain. AB - This research reports on two field studies which demonstrate that self-leadership training decreases strain via increases in self-efficacy and positive affect. The first, an experimental study, found that strain was reduced in the randomly assigned training group, but not in the control group. The second was a longitudinal study and supported the hypotheses that self-efficacy and positive affect mediated the effect of self-leadership training on strain. Our findings extend both self-leadership and stress management literatures by providing a theoretical framework within which the effects of self-leadership on strain can be understood. Practically speaking, our findings suggest that self-leadership training offers an individual-level preventive approach to stress management. PMID- 22308968 TI - Effects of job control and situational severity on the timing of help-seeking. AB - Studies suggest that the psychopathological effects of involvement in critical incidents among emergency service workers failing to seek help in a timely manner may be detrimental both for the individual and for the organization. However, little is known as to the factors governing when individuals seek such help. Consequently, drawing from the help-seeking and coping literatures, we generate a theory explicating how job characteristics (namely, job control) and situational factors (namely, the severity of incident involvement) combine to influence help seeking delay or, in other words, the amount of time that passes before employees seek help for incident-related distress. Using data collected from firefighters who were involved at varying degrees of intensity in the events in and around the World Trade Center on September 11, 2001, we demonstrate that increasing levels of situational severity influence the relationship between job-control and help seeking delay with job control having a curvilinear association with help-seeking delay under conditions of high situational severity. PMID- 22308969 TI - The spillover and crossover of resources among partners: the role of work-self and family-self facilitation. AB - This study tested the positive spillover-crossover model among dual-earner couples. Job resources of 1 partner were predicted to spill over to his/her individual energy, that is, reduced fatigue and increased motivation. Consequently, individual energy was predicted to influence one's partner's family resources, which were hypothesized to influence the partner's level of individual energy. Work-self facilitation and family-self facilitation were hypothesized to mediate the favorable effects of job and home resources, respectively, on individual energy. A sample of 131 couples participated in the study. Structural equation modeling analyses showed that job resources influence one's own individual energy through work-self facilitation. Consequently, the levels of individual energy positively influence one's partner's perception of home resources, which eventually spill over to the partner's individual energy through experienced family-self facilitation. Work-self and family-self facilitation are useful in explaining why job and family resources may enhance the levels of energy that individuals invest in different life domains. PMID- 22308970 TI - The association between job demands/control and health in employed parents: the mediating role of work-to-family interference and enhancement. AB - This paper examined whether work-to-family interference (WFI) and work-to-family enhancement (WFE) mediated the association between job demands/control and self reported mental and physical health. Data were from the Household, Income and Labor Dynamics in Australia survey and included 1,404 Australian adults aged 18 64 years at baseline; 820 participants provided data at three time points (baseline, 12-month follow-up, and 24-month follow-up). Self-report questionnaires assessed mental and physical health, WFI and WFE, and job demands/control. Mediation analyzes performed on the longitudinal data indicated that WFI mediated the relationships between job demands/control and self-reported mental and physical health. The findings have implications for improving the well being of employees and workplace productivity. PMID- 22308971 TI - Epilepsy in Tanzanian children: association with perinatal events and other risk factors. AB - PURPOSE: To define the prevalence and risk factors for epilepsy in children in a rural district of Tanzania by conducting a community-based case-control study. METHODS: Children aged 6-14 years with active epilepsy (at least two unprovoked seizures in the last 5 years) were identified in a cross-sectional survey in Tanzania. Cases were compared with age-matched controls. KEY FINDINGS: Overall 112 children with epilepsy (CWE) were identified; the unadjusted prevalence of epilepsy was 2.91 per 1,000 (95% confidence interval [95% CI] 2.4-3.5). The main seizure types were focal motor with secondary generalization in 73 (65.2%) of 112 and generalized convulsive seizures in 19 (16.9%) of 112. Adverse perinatal events were present in 16 (14%) of 112 cases but in no controls. In multivariate analysis, epilepsy was associated with number of parents who were resident at home (odds ratio [OR] 6.2 for none vs. both resident, 95% CI 1.5-25.5), history of adverse perinatal events (OR 14.9, 95% CI 1.4-151.3), family history of afebrile seizures (OR 5.7, 95% CI 1.0-27.5), and poor scholastic attainment (OR 8.6, 95% CI 4.0-18.4). Electroencephalography (EEG) and computed tomography (CT) scans were abnormal in 44 (44%) of 101 and 26 (29%) of 90 cases, respectively. Overall, 98 (88%) of 112 cases had focal features on assessment. SIGNIFICANCE: In this study from sub-Saharan Africa, CWE predominantly had focal features that support the suggestion that most epilepsy in this region has a symptomatic etiology. Adverse perinatal events were strongly associated with epilepsy. Genetic and social factors may also be important. Epilepsy may be preventable in a significant proportion of children with better antenatal and perinatal care. PMID- 22308972 TI - Plant uptake of atmospheric brominated flame retardants at an E-waste site in southern China. AB - Brominated flame retardants (BFRs) were measured in eucalyptus leaves and pine needles as well as the leaf surface particles (LSPs) of the two species at an e waste site in southern China in 2007-2008. The monthly concentrations of total BFRs in the eucalyptus leaves and pine needles were in range of 30.6-154 and 15.1 236 ng/g dry weight, respectively, and relatively higher concentrations were observed in winter and spring. Correlation analysis of BFR concentrations and comparison of PBDE compositions between the plants and LSPs, air (gaseous and particle-bound phases), and ambient variables were conducted. The results revealed that BFRs in the plants, especially for less brominated BFRs, showed positive relationships with BFRs in the LSPs and negative relationships with the gaseous BFRs and ambient temperature. The PBDE profiles in the plants were similar to the gaseous profile for low brominated BDEs (di- through hexa-BDEs) and to the LSP profiles for highly brominated BDEs (hepta- through deca-BDEs). Applying McLachlan's framework to our data suggests that the uptake of BFRs was controlled primarily by gaseous partitioning equilibrium for compounds with log octanol-air partition coefficients (K(OA)) < 12 and by particle-bound deposition for compounds with log K(OA) > 13. Different relationships between the plant/air partition coefficient (K(PA)) and K(OA), which depend on the uptake mechanisms, were observed for polybrominated diphenyl ethers (PBDEs). This paper adds to the current knowledge of the factors and mechanisms governing plant uptake of semivolatile organic compounds with relatively high K(OA) in the environment. PMID- 22308973 TI - Genetic variants associated with predisposition to prostate cancer and potential clinical implications. AB - Prostate cancer is the commonest cancer in the developed world. There is an inherited component to this disease as shown in familial and twin studies. However, the discovery of these variants has been difficult. The emergence of genome-wide association studies has led to the identification of over 46 susceptibility loci. Their clinical utility to predict risk, response to treatment, or treatment toxicity, remains undefined. Large consortia are needed to achieve adequate statistical power to answer these genetic-clinical and genetic-epidemiological questions. International collaborations are currently underway to link genetic with clinical/epidemiological data to develop risk prediction models, which could direct screening and treatment programs. PMID- 22308974 TI - Impact of anxiety and depression on disease control and quality of life in asthma patients. AB - INTRODUCTION: Patients with asthma also tend to have anxiety and depression. These comorbidities may affect asthma control and quality of life. The objective of this study was to assess the impact of anxiety and depression on asthma control and quality of life. PATIENTS AND METHODS: Cross-sectional study of asthma outpatients was conducted at two hospitals in the Basque Country (northern Spain). Data collected included sociodemographic variables, asthma symptoms, treatment, number of exacerbations, level of control, quality of life, presence of psychological morbidities, and level of physical activity. Spirometry was performed in accordance with the recommendations of the Spanish Society of Pneumology and Thoracic Surgery. RESULTS: Among 354 asthmatics, 77% had poor or partial control of their condition, 31% had anxiety alone, 2% had depression alone, and 10% had anxiety plus depression. Poor asthma control was associated with anxiety plus depression (odds ratio (OR): 3.61; 95% confidence interval (CI): 1.05-12.41) as well as with female patients (OR: 1.85; 95% CI: 1.11-3.10). Anxiety had an independent effect on reduced quality of life across all domains; anxiety plus depression had an even greater effect. CONCLUSION: Among patients with asthma, anxiety and depression adversely affect asthma control and quality of life, raising the possibility that treating these psychological comorbidities could improve asthma control and quality of life. PMID- 22308975 TI - Perineal hernia repair after abdominoperineal resection: a pooled analysis. AB - AIM: The purpose of this study was to determine treatment characteristics and clinical outcome for patients with perineal hernia after abdominoperineal excision (APE). METHOD: A systematic search of the literature revealed 40 individually documented patients, published between 1944 and 2010. Three additional patients treated at our centre were added. Patient characteristics, type of repair and outcome were entered into a database and a pooled analysis of these 43 patients was performed. RESULTS: The pooled analysis revealed a median time interval of 8 months between APE and surgical repair of perineal hernia. The surgical approaches were perineal in 22 patients, open abdominal in 11, open abdominoperineal in three, laparoscopic in five and laparoscopic-perineal in two patients. A primary recurrence was documented in 13 patients and a second recurrence in three. The recurrence rate was 5/25 for synthetic or biological mesh, 6/12 for primary closure and 2/6 for the remaining techniques. Recurrent perineal hernia was repaired using a synthetic or biological mesh (n = 6), primary closure (n = 5) or a muscle flap (gluteus or gracilis; n = 4). CONCLUSION: From these limited and biased data based on published case descriptions, it appears that the recurrence rate of primary perineal hernia repair after APE is lower with the use of a mesh or other assisted closure than with primary suture repair. PMID- 22308976 TI - Evaluation of direct in vivo gene transfer in an equine metacarpal IV ostectomy model using an adenoviral vector encoding the bone morphogenetic protein-2 and protein-7 gene. AB - OBJECTIVE: To evaluate gene transfer in an equine metacarpal IV (MCIV) ostectomy model using adenoviral vectors encoding the human bone morphogenetic protein-2 and protein-7 gene (Ad-BMP-2/-7). STUDY DESIGN: EXPERIMENTAL ANIMALS: Healthy adult horses (n = 15). METHODS: A plate stabilized, critical size 1.5 cm ostectomy was created in left and right MCIV. The ostectomy site was injected with either Ad-green fluorescent protein (Ad-GFP) or Ad-hBMP-2/-7 at completion of surgery; the same treatment was assigned to both the left and right forelimb of each horse (n = 5 horses/group). Bone healing was evaluated radiographically every 2 weeks for 16 weeks. Horses in a pilot study (n = 5) were used as untreated controls for radiographic evaluation to 8 weeks. After euthanasia at 16 weeks bone healing was evaluated using dual energy X-ray absorptiometry (DEXA) and histomorphometry. Data were analyzed using an ANOVA or Kruskal-Wallis test. Level of significance was P < .05. RESULTS: At 4 and 6 weeks, the Ad-GFP group had a significantly lower percentage defect ossification compared with the untreated control group. There was no significant difference between untreated and Ad-hBMP-2/-7 groups at any time point and no significant difference in bone healing radiographically, histologically, or using DEXA between any groups at 16 weeks. CONCLUSIONS: Ad-hBMP-2/-7 did not improve bone healing in horses at 16 weeks. PMID- 22308977 TI - Recruited minced skin grafting for improving the skin appearance of the donor site of a split-thickness skin graft. AB - OBJECTIVE: To improve skin appearance at the donor site of a split-thickness skin graft, part of the harvested skin was minced and grafted back onto the site in a process we named "recruited minced skin grafting." MATERIALS AND METHODS: Thirteen Japanese patients who needed split-thickness skin grafts were treated with recruited minced skin grafting. Five patients were used as controls, in whom donor sites were treated with the traditional method. Part of the split-thickness skin was minced using two surgical blades (number 24) to an approximate particle size of less than 0.5 mm. Minced skin was spread and transplanted onto the donor site and covered with polyurethane foam. Twelve months after the operation, donor sites were scored for hypopigmentation, hyperpigmentation, redness, and disruption of skin texture. Gross appearance was evaluated according to total score. RESULTS: Donor sites treated with recruited minced skin grafts had significantly better appearance than those of controls. Donor sites that had more than 5% of the total area treated tended to have better results. CONCLUSION: Recruited minced skin grafting is a good method of improving the appearance of the donor site. PMID- 22308978 TI - Feasibility of transradial coronary angiography and intervention using a single Ikari left guiding catheter for ST elevation myocardial infarction. AB - BACKGROUND: Transradial coronary intervention (TRI) has been widely adopted in ST elevation myocardial infarction (STEMI) patients but there is limited literature on the use of a single catheter for both diagnostic angiography and intervention. We aim to evaluate the feasibility and outcomes of TRI with a single Ikari left (IL) guiding catheter in STEMI patients. METHODS: This is a retrospective study of 362 consecutive STEMI patients from August 2007 to December 2008. We assessed the feasibility of TRI with a single IL and compared this strategy with conventional transfemoral intervention (TFI) on the following outcomes: (1) door to perfusion time, (2) total procedural duration, (3) total fluoroscopy duration, and (4) major adverse cardiac events (MACE) by intention to treat analysis. RESULTS: TRI was attempted in 185 patients. There were no failed radial cannulations. Overall success rate of primary TRI with a single IL was 96.9% and there were only 2 failures that required conversion to TFI. Compared to TFI, TRI with IL tended to a shorter median door to perfusion time, 90 (IQR 76.0 - 119.5) versus 98 (IQR 80.8 - 120.5) minutes (P = 0.07) and a shorter median procedure duration of 34 (IQR 27.0 - 45.0) versus 37 (IQR 28.0 - 49.3) minutes (P = 0.06). The median fluoroscopy duration was longer in the TRI group. MACE were comparable between the 2 groups. CONCLUSION: In experienced centers, TRI with a single IL catheter for STEMI is a feasible and effective approach and outcomes are comparable to conventional TFI. PMID- 22308979 TI - The dynamic healing profile of human periodontal ligament stem cells: histological and immunohistochemical analysis using an ectopic transplantation model. AB - BACKGROUND AND OBJECTIVE: Human periodontal ligament stem cells (hPDLSCs) have been reported to play the pivotal role in periodontal regeneration. However, the dynamic cellular healing process initiated by hPDLSCs still remains to be elucidated. In the present study, the sequence of regeneration by hPDLSCs was assessed using histological and immunohistochemical observation in an ectopic transplantation model, which is a well-standardized assessment tool that excludes the innate healing factors from the animals. MATERIAL AND METHODS: Human periodontal ligament stem cells that were isolated and characterized from teeth (n=12) extracted for the purpose of orthodontic treatment were transplanted with carriers into ectopic subcutaneous pouches in immunocompromised mice (n=20). Animals were killed after several different healing periods: 3 d (n=4), 1 (n=4), 2 (n=4), 4 (n=4) and 8 wk (n=4). Histological analysis for regenerated tissues formed by hPDLSCs was conducted using hematoxylin and eosin, Masson's trichrome and picrosirius red staining. In addition, immunohistochemical staining was performed to observe the sequential expression of osteogenic/cementogenic and periodontal ligament tissue-specific markers associated with periodontal regeneration. RESULTS: The whole healing process by transplanted hPDLSCs could be broadly divided into four distinctive phases. In the first phase, proliferated hPDLSCs migrated evenly all over the carrier, and collagenous tissues appeared in the form of amorphous collagen matrices. In the second phase, collagen fibers were well arranged among the carriers, and cementoid-like tissues were observed. In the third phase, the formation of mature collagen fibers, resembling Sharpey's fibers, was associated with active mineralization of cementum-like tissues, and in the fourth phase, the maturation of cementum-like tissues was observed on carrier surfaces. Various osteogenic/cementogenic markers related to the regeneration processes were expressed in a well-orchestrated time order. Interestingly, well-organized cementum-like and periodontal ligament fiber-like tissues and cells with early and late osteogenic/cementogenic markers were frequently observed in the secluded area of carrier surfaces. We termed this area the cell-rich zone. CONCLUSION: The results from this study clearly demonstrated the sequential histological changes during periodontal tissue regeneration by hPDLSCs. Understanding of this process would potentially enable us to develop better cell-based treatment techniques. PMID- 22308980 TI - Differential expression pattern of ISG15 in different tissue explants and cells induced by various interferons. AB - Interferon stimulated gene 15 (ISG15), an ubiquitin cross-reactive protein, can conjugate to target proteins. Unlike ubiquitination, protein modification by ISG15 does not target protein for degradation, but enhances the cellular response to interferon (IFN), which plays a key role in antiviral responses. In this study, Western blot and/or immunocytochemistry were performed to explore the ISG15 expression patterns in explants of bovine endometrium, mammary gland and kidney, as well as Madin-Darby bovine kidney (MDBK), endometrial and mammary cells stimulated by IFN-alpha, -beta, and -tau. Western blot indicated that there are differential minimum antiviral units among recombinant bovine interferon alpha (rbIFN-alpha, 10(2) IU/mL), rbIFN-beta (10(3) IU/mL) and rbIFN-tau (10(4) IU/mL) in regard to stimulating saturation expression of free and ISG15 conjugated proteins by MDBK cells and endometrial and mammary explants. These results were further confirmed through immunocytochemical analysis of MDBK, endometrial and mammary cells. For the first time it has been shown that the expression pattern of ISG15-conjugated proteins occurs in a tissue-specific manner. Furthermore, the present findings provide the first evidence of 10- to 100-fold differences in minimum antiviral units of rbIFN-alpha, rbIFN-beta, and rbIFN-tau in regard to stimulating saturation expression of ISG15. PMID- 22308981 TI - The improvement in quality of life and life expectancy of people with diabetes increasingly depends on the success of innovative people in academia and industry to develop new technologies. Preface. PMID- 22308982 TI - Self-monitoring of blood glucose. PMID- 22308983 TI - Continuous glucose monitoring in 2011. PMID- 22308984 TI - Insulin pumps. PMID- 22308985 TI - Closing the loop. PMID- 22308986 TI - New insulins and insulin therapy. PMID- 22308987 TI - New ways of insulin delivery. PMID- 22308988 TI - Using health information technology to prevent and treat diabetes. PMID- 22308989 TI - Technology and pregnancy. PMID- 22308990 TI - Type 1 diabetes mellitus: immune intervention. PMID- 22308991 TI - Advances in exercise, physical activity and diabetes mellitus. PMID- 22308992 TI - Diabetes technology and treatment in the paediatric age group. PMID- 22308993 TI - Diabetes technology and the human factor. PMID- 22308994 TI - New medications for the treatment of diabetes. PMID- 22308996 TI - Foxp3+ T cells in peripheral blood of renal transplant recipients and clinical correlations. AB - AIM: Immunophenotype peripheral blood T cells from renal transplant recipients (RTR) using cellular markers of regulatory T cells (Tregs) and flow cytometry, including Foxp3, and correlate these findings with clinical parameters. METHODS: Expression of phenotypic markers of Tregs was assessed by flow cytometric analysis of peripheral blood lymphocytes (PBL) from (i) RTR (n = 95); (ii) patients with end-stage renal failure (ESRF) awaiting transplantation (n = 17); and (iii) normal healthy controls (n = 18). RESULTS: The percentage of CD4(+) CD25(+) Foxp3(+) cells within the CD4(+) cell population did not significantly alter at different time points post-transplant. However, the percentage of CD4(+) CD25(+) Foxp3(+) cells within the CD4(+) population was significantly lower in RTR compared with patients with ESRF. In contrast, RTR and ESRF had a similar percentage of CD4(+) CD25(+) cells expressing Foxp3. Multivariate analysis of PBL and clinical parameters demonstrated (i) a positive linear relationship between the percentage CD4(+) CD25(+) cells expressing Foxp3 and estimated glomerular filtration rate and (ii) a higher percentage of CD4(+) CD25(+) cells in the CD4(+) cell population in patients with malignancy (the majority were skin cancers). Malignancy also correlated strongly with time post-transplant and age of the RTR. CONCLUSION: Immune monitoring of the PBL phenotype in RTR using CD4, CD25 and Foxp3 may stratify RTR and predict graft outcome and function, and risk of complications from immunosuppression. Longitudinal and functional studies of Tregs are essential to extend the findings of the present study. PMID- 22308997 TI - Assessing the associative deficit of older adults in long-term and short term/working memory. AB - Older adults exhibit a deficit in associative long-term memory relative to younger adults. However, the literature is inconclusive regarding whether this deficit is attenuated in short-term/working memory. To elucidate the issue, three experiments assessed younger and older adults' item and interitem associative memory and the effects of several variables that might potentially contribute to the inconsistent pattern of results in previous studies. In Experiment 1, participants were tested on item and associative recognition memory with both long-term and short-term retention intervals in a single, continuous recognition paradigm. There was an associative deficit for older adults in the short-term and long-term intervals. Using only short-term intervals, Experiment 2 utilized mixed and blocked test designs to examine the effect of test event salience. Blocking the test did not attenuate the age-related associative deficit seen in the mixed test blocks. Finally, an age-related associative deficit was found in Experiment 3, under both sequential and simultaneous presentation conditions. Even while accounting for some methodological issues, the associative deficit of older adults is evident in short-term/working memory. PMID- 22308998 TI - Aging and the memorial consequences of catching contradictions with prior knowledge. AB - This experiment tested the possibility that older adults are less susceptible to semantic illusions because they are more likely to notice contradictions with stored knowledge. Older and young adults encoded stories containing factual inaccuracies; critically, half the participants were instructed to mark any errors they noticed. Older adults reproduced fewer story-errors on a later general knowledge test, but there were no age differences in marking errors during encoding. However, older adults were better able to recover and answer correctly after failing to notice errors during story-reading. Implications for false memories and semantic illusions are discussed. PMID- 22308999 TI - Enacted support during stressful life events in middle and older adulthood: an examination of the interpersonal context. AB - Individuals often turn to their close social ties for support during stressful life events. Although a great deal of work examines perceived support (i.e., support believed to be available should an event occur), less is known about enacted support (i.e., support actually provided during stressful events), especially among middle-aged and older people. The present study investigated whether enacted support (emotional or instrumental) varies by relationship quality and stress appraisals. Participants included 152 adults (principal respondents; aged 50 to 69 years, 63% women) who had experienced three or more stressful life events in the last year and 180 of their identified supportive ties (core network members). Multilevel models revealed that higher quality relationships enact high levels of support irrespective of high or low stress appraisals. In contrast, lower quality relationships enact greater support under conditions of higher stress but less support under conditions of lower stress, suggesting that lower quality relationships are mobilized only under higher levels of stress. Findings are consistent with the support provision process model and highlight the importance of considering relationship context and the stress continuum in studies of enacted support among older adults. PMID- 22309000 TI - Examining the potential for gender bias in the prediction of symptom validity test failure by MMPI-2 symptom validity scale scores. AB - Using a sample of individuals undergoing medico-legal evaluations (690 men, 519 women), the present study extended past research on potential gender biases for scores of the Symptom Validity (FBS) scale of the Minnesota Multiphasic Personality Inventory-2 by examining score- and item-level differences between men and women and determining the extent to which FBS scores were able to correctly identify men and women who were divided into credible responders (n = 837) and noncredible responders (n = 372) on the basis of performance on symptom validity tests. Results indicated that women had slightly higher raw FBS scores than men (d = .29), and significant differences between men and women in item endorsement were demonstrated for 14 FBS items. Step-down hierarchical logistic regression procedures indicated predictive bias (chi2Delta = 23.72, p < .001). Follow-up analyses indicated intercept bias (chi2Delta = 23.51, p < .001) but not slope bias (chi2Delta = 0.22, p = .64). However, using the test publisher's recommended FBS cutoff scores (Ben-Porath, Graham, & Tellegen, 2009), classification accuracies were similar for women and men (T > 80, h = -.02; T > 100, h = -.22, respectively). On the basis of these results, we conclude there is no evidence of clinically meaningful bias in predictions of symptom validity test failure made using FBS scores for men and women. PMID- 22309001 TI - Are clinical diagnoses of Alzheimer's disease and other dementias affected by education and self-reported race? AB - A randomized controlled trial examined whether the diagnostic process for Alzheimer's disease and other dementias may be influenced by knowledge of the patient's education and/or self-reported race. Four conditions were implemented: diagnostic team knows (a) race and education, (b) education only, (c) race only, or (d) neither. Diagnosis and clinical staging was established at baseline, at Wave 2, and for a random sample of Wave 3 respondents by a consensus panel. At study end, a longitudinal, "gold standard" diagnosis was made for patients with follow-up data (71%). Group differences in Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) diagnosis were estimated using logistic regression and generalized estimating equations. Sensitivity and specificity were examined for baseline diagnosis in relation to the gold standard, longitudinal diagnosis. Despite equivalent status on all measured variables across waves, members of the "knows race only" group were less likely than those of other groups to receive a diagnosis of dementia. At final diagnosis, 19% of the "knows race only" group was diagnosed with dementia versus 38% to 40% in the other 3 conditions (p = .038). Examination of sensitivities and specificities of baseline diagnosis in relation to the gold standard diagnosis showed a nonsignificant trend for lower sensitivities in the knowing race conditions (0.3846), as contrasted with knowing education only (0.480) or neither (0.600). The finding that knowledge of race may influence the diagnostic process in some unknown way is timely, given the recent State-of-the-Science conference on Alzheimer's disease prevention, the authors of which called for information about and standardization of the diagnostic process. PMID- 22309002 TI - Influence of the medial offset of the proximal humerus on the glenohumeral destabilising forces during arm elevation: a numerical sensitivity study. AB - This study assessed the influence of the medial offset of the proximal humerus on the glenohumeral destabilising forces during arm elevation in the plane of the scapula, using the AnyBody Modeling System. The variability of the medial offset was covered using literature data (minimum, 0 mm; average, 7 mm and maximum, 14 mm). The following parameters were studied: moment arm (MA; middle deltoid), muscle activity and stability ratios. The minimum offset decreased the MA of the middle deltoid ( -11%), increased its activation (+18%) and its superior destabilising action (+40%). The maximum offset had an opposite effect (+9%, -30% and -30%). The stabilising action of the rotator cuff was not affected. Varying the medial offset seems to have an influence on the destabilising action of the middle deltoid. The AnyBody simulation tool appears to be promising in establishing links between shoulder morphology and stability. PMID- 22309003 TI - Blood pressure reducing effects of Phalaris canariensis in normotensive and spontaneously hypertensive rats. AB - The birdseed Phalaris canariensis (Pc) is popularly used as an antihypertensive agent. The aqueous extract of Pc (AEPc) was administered in adult normotensive Wistar rats and spontaneously hypertensive rats (SHR) and in prehypertensive young SHR (SHR(Y), 3 weeks old). Animals received AEPc (400 mg.kg(-1).day(-1), by gavage) for 30 days, then groups were divided into 2 subgroups: one was treated for another 30 days and the other received water instead of AEPc for 30 days. AEPc reduced systolic blood pressure (SBP) in both adult groups; however, treatment interruption was followed by a gradual return of the SBP to baseline levels. SHR(Y) became hypertensive 30 days after weaning. AEPc minimized the increase in SBP in SHR(Y), but blood pressure rose to levels similar to those in the untreated group with treatment interruption. There were no changes in renal function, diuresis, or Na(+) excretion. Pc is rich in tryptophan, and the inhibition of the metabolism of tryptophan to kynurenine, a potential vasodilator factor, prevented the blood pressure reducing effect of AEPc. Moreover, AEPc significantly reduced sympathoexcitation. Data indicate that the metabolic derivative of tryptophan, kynurenine, may be a mediator of the volume-independent antihypertensive effect of Pc, which was at least in part mediated by suppression of the sympathetic tonus. PMID- 22309005 TI - Wildlife, trade, susceptibility amplify food risks. PMID- 22309006 TI - Veterinary medicine in the global community. PMID- 22309007 TI - What is your diagnosis? Splenic myelolipoma. PMID- 22309008 TI - Diagnostic imaging in veterinary dental practice. PMID- 22309009 TI - Pathology in practice. Focally extensive granulomatous and eosinophilic conjunctivitis with numerous intralesional nematodes, consistent with Onchocerca spp. PMID- 22309010 TI - Pathology in practice. Widespread, metastatic liposarcoma and moderate, acute, diffuse centrilobular hepatic necrosis. PMID- 22309011 TI - Injuries and illnesses among urban search-and-rescue dogs deployed to Haiti following the January 12, 2010, earthquake. AB - OBJECTIVE: To establish types and rates of injuries and illnesses among urban search-and-rescue (USAR) dogs deployed to Haiti following the January 12, 2010, earthquake. DESIGN: Cross-sectional survey. ANIMALS: 23 Federal Emergency Management Agency (FEMA) USAR dogs deployed to Haiti. PROCEDURES: An online survey was distributed to the handlers of all FEMA USAR dogs deployed to Haiti in response to the January 12, 2010, earthquake. RESULTS: Of 33 handlers with 37 dogs that deployed, 19 (58%) handlers completed the survey, providing information on 23 (62%) dogs. Injuries and illnesses were reported in 10 of the 23 (43%) dogs, 8 of which had multiple issues. Dogs worked a total of 250 days and 1,785 hours. Dehydration and wounding were the most common disorders, with incidences of 3.9 and 3.4 events/1,000 h worked, respectively. Other disorders included ocular discharge and appetite decrease (incidence of each, 1.1 events/1,000 h worked) and weight loss, urination changes, skin infection, ear infection, oral abscess, and nonspecific illness (incidence of each, 0.56 events/1,000 h worked). Overall, there were 12.6 events/1,000 h worked. All health issues were minor and resolved during the deployment or within 2 weeks after demobilization. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that many of the USAR dogs deployed to Haiti developed acute injuries and illnesses. However, despite the high heat index, long hours worked, and dusty conditions, most injuries and illnesses were minor and all had resolved within 14 days. When logistic supplies for USAR teams are limited, minimal basic medical needs to treat common injuries should be a priority. PMID- 22309012 TI - Clinical efficacy and safety of dexmedetomidine used as a preanesthetic prior to general anesthesia in cats. AB - OBJECTIVE: To evaluate the clinical efficacy of dexmedetomidine as a preanesthetic medication administered prior to anesthetic induction with ketamine or propofol and with or without isoflurane for maintenance of anesthesia. DESIGN: Randomized, blinded, controlled clinical trial. ANIMALS: 184 client-owned cats. PROCEDURES: Cats requiring general anesthesia for short or long procedures were assigned to receive 1 of 4 preanesthetic and induction drug combinations (dexmedetomidine and ketamine, placebo [saline {0.9% NaCl} solution] and ketamine, dexmedetomidine and propofol, or placebo and propofol). Cats undergoing long procedures received isoflurane for maintenance of anesthesia. RESULTS: Administration of dexmedetomidine prior to anesthetic induction with ketamine significantly increased the intubation success rate (57/64 [89%]), compared with the success rate for the placebo (4/37 [11 %]); significantly reduced the median induction dose of propofol (<= 5.1 mg/kg [2.32 mg/lb]), compared with that for the placebo (<= 10.5 mg/kg [4.77 mg/lb]); and significantly reduced the isoflurane concentration (1.5%) required for anesthesia maintenance, compared with that for the placebo (3.0%). Postoperatively, fewer cats receiving dexmedetomidine required rescue analgesia, and cats had lower pain scores for at least 2 hours after surgery, compared with results for cats receiving the placebo. Heart rate was lower during the procedure and respiratory rate and rectal temperature were lower during and after the procedure for cats receiving dexmedetomidine. More cats that received dexmedetomidine had emesis and pale mucous membranes, compared with the number of cats with those signs that received placebo. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine as a preanesthetic was efficacious for clinical use in cats requiring general anesthesia. PMID- 22309013 TI - Evaluation of dietary energy intake and physical activity in dogs undergoing a controlled weight-loss program. AB - OBJECTIVE: To quantify physical activity and dietary energy intake in dogs enrolled in a controlled weight-loss program and assess relationships between energy intake and physical activity, sex, age, body weight, and body condition score (BCS). DESIGN: Prospective clinical study. ANIMALS: 35 client-owned obese dogs (BCS > 7/9). PROCEDURES: Dogs were fed a therapeutic diet with energy intake restrictions to maintain weight loss of approximately 2%/wk. Collar-mounted pedometers were used to record the number of steps taken daily as a measure of activity. Body weight and BCS were assessed at the beginning of the weight-loss program and every 2 weeks thereafter throughout the study. Relationships between energy intake and sex, age, activity, BCS, and body weight at the end of the study were assessed via multivariable linear regression. Variables were compared among dogs stratified post hoc into inactive and active groups on the basis of mean number of steps taken (< or > 7,250 steps/d, respectively). RESULTS: Mean +/ SD daily energy intake per unit of metabolic body weight (kg(0.75)) of active dogs was significantly greater than that of inactive dogs (53.6 +/- 15.2 kcal/kg(0.75) vs 42.2 +/- 9.7 kcal/kg(0.75), respectively) while maintaining weight-loss goals. In regression analysis, only the number of steps per day was significantly associated with energy intake. CONCLUSIONS AND CLINICAL RELEVANCE: Increased physical activity was associated with higher energy intake while maintaining weight-loss goals. Each 1,000-step interval was associated with a 1 kcal/kg(0.75) increase in energy intake. PMID- 22309014 TI - Pneumoesophagography and the appearance of masses in the caudal portion of the esophagus in dogs with spirocercosis. AB - OBJECTIVE: To determine the usefulness of pneumoesophagography, compared with that of survey radiography, for characterization of esophageal pathological changes in dogs with endoscopically confirmed intraluminal Spirocerca lupi nodules in the caudal portion of the esophagus. DESIGN: Diagnostic test evaluation. ANIMALS: 30 dogs with endoscopically confirmed spirocercosis. PROCEDURES: Dorsoventral (DV) and right lateral recumbent (RLR) thoracic survey radiographs were obtained for each dog. Endoscopy was subsequently performed, the esophagus was inflated with air, and left lateral recumbent, RLR, DV, and ventrodorsal thoracic radiographs were obtained. The amount of esophageal and gastric distention was recorded. Visibility, location, and surface characteristics of lesions and total length of esophageal involvement were recorded independently for each radiograph and modality and compared with each other. RESULTS: Survey DV radiographs were more reliable than survey RLR radiographs for detecting caudal esophageal pathological changes. Lateral pneumoesophagograms showed more esophageal air and had more visible nodules than did their orthogonal counterparts. Right lateral recumbent pneumoesophagograms allowed for evaluation of the air-filled stomach, particularly the cardiac portion, for additional pathological changes. Pneumoesophagography allowed the mural position (47% located dorsally) and surface characteristics of Spirocerca nodules to be determined. Six of 9 dogs with confirmed malignant disease had an irregular nodule surface suggestive of neoplastic transformation. CONCLUSIONS AND CLINICAL RELEVANCE: Pneumoesophagography was easily performed in dogs with spirocercosis and showed promise as a cost-effective and safe initial diagnostic procedure for further evaluation and characterization of suspected caudal esophageal lesions. PMID- 22309015 TI - Effect of veterinarian-client-patient interactions on client adherence to dentistry and surgery recommendations in companion-animal practice. AB - OBJECTIVE: To explore the relationship between veterinarian-client-patient interactions and client adherence to dental and surgery recommendations and to test the a priori hypotheses that appointment-specific client satisfaction and relationship-centered care are positively associated with client adherence. DESIGN: Cross-sectional study. SAMPLE: A subsample of 19 companion-animal veterinarians and 83 clients from a larger observational study consisting of 20 randomly recruited veterinarians and a convenience sample of 350 clients from eastern Ontario. PROCEDURES: Videotaped veterinarian-client-patient interactions containing a dentistry recommendation, surgery recommendation, or both were selected for inclusion from the larger sample of interactions coded with the Roter interaction analysis system. Client adherence was measured by evaluating each patient's medical record approximately 6 months after the videotaped interaction. The clarity of the recommendation, appointment-specific client satisfaction score, and relationship-centered care score were compared between adhering and nonadhering clients. RESULTS: Among the 83 veterinarian-client patient interactions, 25 (30%) clients adhered to a dentistry recommendation, surgery recommendation, or both. The odds for adherence were 7 times as great for clients who received a clear recommendation, compared with clients who received an ambiguous recommendation from their veterinarian. Moreover, adhering clients were significantly more satisfied as measured after the interview. Interactions resulting in client adherence also had higher scores for relationship-centered care than did interactions leading to nonadherence. CONCLUSIONS AND CLINICAL RELEVANCE: Veterinarian use of a relationship-centered care approach, characterized as a collaborative partnership between a veterinarian and a client with provision of clear recommendations and effective communication of the rationale for the recommendations, has positive implications for client adherence. PMID- 22309016 TI - Surveillance of bacterial contamination in small animal veterinary hospitals with special focus on antimicrobial resistance and virulence traits of enterococci. AB - OBJECTIVE: To determine the prevalence of bacterial contamination on 4 surfaces of 4 types of standard equipment in small animal veterinary hospitals. DESIGN: Surveillance study. SAMPLE: 10 small animal veterinary hospitals. PROCEDURES: Each hospital was visited 3 times at 4-month intervals; at each visit, a cage door, stethoscope, rectal thermometer, and mouth gag were swabbed. Swab samples were each plated onto media for culture of enterococci and organisms in the family Enterobacteriaceae. Enterococci were identified via a species-specific PCR assay and sodA gene sequencing; species of Enterobacteriaceae were identified with a biochemical test kit. Antimicrobial susceptibility was assessed via the disk diffusion method. Enterococci were screened for virulence traits and genotyped to assess clonality. RESULTS: Among the 10 hospitals, enterococci were isolated from cage doors in 7, from stethoscopes in 7, from thermometers in 6, and from mouth gags in 1; contamination with species of Enterobacteriaceae was rare. Enterococci were mainly represented by Enterococcus faecium (35.4%), Enterococcus faecalis (33.2%), and Enterococcus hirae (28.3%). Antimicrobial resistance was common in E. faecium, whereas virulence traits were present in 99% of E. faecalis isolates but not in E. faecium isolates. Clonal multidrug resistant E. faecium was isolated from several surfaces at 1 hospital over multiple visits, whereas sporadic nonclonal contamination was detected in other hospitals. CONCLUSIONS AND CLINICAL RELEVANCE: Contamination of surfaces in small animal veterinary hospitals with multidrug-resistant enterococci is a potential concern for pets and humans contacting these surfaces. Implementing precautions to minimize enterococcal contamination on these surfaces is recommended. PMID- 22309017 TI - Transitional cell carcinoma involving the ductus deferens in a dog. AB - CASE DESCRIPTION: A 12-year-old neutered male Springer Spaniel was referred with a 1-year history of recurring urinary tract infections. Repeated treatment with appropriate antimicrobials selected on the basis of bacterial culture and antimicrobial susceptibility results would result in clinical improvement, but recurrence of clinical signs was observed within days after discontinuation of treatment. CLINICAL FINDINGS: Ultrasound examination revealed a tubular, fluid filled structure dorsal to the bladder that extended from the midlevel of the bladder to the cranial pole of the prostate. Mineralized foci within a heterogeneous prostatic parenchyma were also noted. Dilation of the right ductus deferens (DD) was observed during exploratory laparotomy. TREATMENT AND OUTCOME: Both DD were surgically removed, and the prostate was biopsied. The histopathological diagnosis was transitional cell carcinoma involving the right DD and the prostate. The dog was treated with meloxicam (0.1 mg/kg [0.05 mg/lb], p.o., q 24 h) for 9 months after diagnosis before being euthanized. CLINICAL RELEVANCE: Because the normal DD is rarely visualized during abdominal ultrasonography in dogs, identification of a tubular, fluid-filled structure dorsal to the bladder may indicate an abnormal DD. Transitional cell carcinoma of the DD should be included in the differential diagnoses of affected patients examined for clinical signs involving the urinary tract. PMID- 22309018 TI - Unusual perianesthetic malignant hyperthermia in a dog. AB - CASE DESCRIPTION: A 7-month-old male Siberian Husky affected by lower motor neuron tetraparesis was anesthetized for electrodiagnostic testing and collection of muscle and nerve biopsy specimens. CLINICAL FINDINGS: Preanesthetic physical examination revealed a high rectal temperature, and serum biochemical analysis revealed high muscle and liver enzyme activities. The dog was anesthetized twice. The dog was anesthetized with isoflurane and developed moderate hypercarbia and mild hyperthermia. Injectable anesthetic agents were used to anesthetize the dog the second time, during which the dog developed severe malignant hyperthermia. A genetic test performed after anesthesia did not reveal a mutation of the RYR1 gene, the gene that mediates calcium-release channels in skeletal muscle. On the basis of clinical features, and because other neuromuscular disorders were ruled out, a genetic channelopathy involving the skeletal muscle ion channels was suspected. TREATMENT AND OUTCOME: The dog was disconnected from the breathing system, and active cooling of the body was performed with ice packs applied to the body surface and alcohol applied to the foot pads. Cold crystalloid solutions were administered i.v.. Intermittent positive-pressure ventilation with 100% oxygen was performed to decrease end-tidal partial pressure of carbon dioxide. Because dantrolene was not available, acepromazine was administered to facilitate a decrease in body temperature. The dog recovered from malignant hyperthermia and was discharged to the owner after 13 days of hospitalization. CLINICAL RELEVANCE: Dogs affected by genetic muscle disorders should be considered at risk for perianesthetic malignant hyperthermia, even in the absence of an RYR1 gene mutation. PMID- 22309019 TI - Acute compartment syndrome in the pelvic limb of a cow following biopsy of a skeletal muscle-associated hemangiosarcoma. AB - CASE DESCRIPTION: A 6-year-old Holstein cow was examined because of chronic lameness and swelling near the stifle joint of the left pelvic limb. CLINICAL FINDINGS: A mass was palpated in the soft tissues lateral to the proximal aspect of the left tibia. Multiple attempts to obtain a biopsy specimen of the mass resulted in acute compartment syndrome of the femoral compartment (tensor fasciae latae and biceps femoris muscles) and lateral tibial compartment (cranial tibial and peroneus tertius muscles) with associated sciatic nerve paralysis. TREATMENT AND OUTCOME: Surgical decompression via tensor fasciae latae and biceps femoris incision resolved the sciatic nerve paralysis. On the fifth day following surgery, the cow began to develop signs of increased respiratory effort. Thoracic radiography revealed a pulmonary metastatic micronodular pattern. The cow was euthanized because its condition deteriorated. Metastatic hemangiosarcoma was confirmed at necropsy, and the primary tumor was the mass that was lateral to the tibia and within the biceps femoris muscle. CLINICAL RELEVANCE: Hemangiosarcoma should be considered a differential diagnosis for lameness in cattle when no orthopedic cause can be identified. Close patient surveillance is strongly recommended in the event that a vascular tumor is present because catastrophic consequences are possible. To our knowledge, this is the first report of acute compartment syndrome in a pelvic limb of a bovine patient and the only report of hemangiosarcoma in the skeletal muscle of cattle. PMID- 22309020 TI - The role of endogenous H2S in cardiovascular physiology. AB - Recent research has shown that the endogenous gas hydrogen sulphide (H2S) is a signalling molecule of considerable biological potential and has been suggested to be involved in a vast number of physiological processes. In the vascular system, H2S is synthesized from cysteine by cystathionine-gamma-lyase (CSE) in smooth muscle cells (SMC) and 3- mercaptopyruvate sulfuresterase (3MST) and CSE in the endothelial cells. In pulmonary and systemic arteries, H2S induces relaxation and/or contraction dependent on the concentration of H2S, type of vessel and species. H2S relaxes SMC through a direct effect on KATP-channels or Kv-channels causing hyperpolarization and closure of voltage-dependent Ca2+ channels followed by a reduction in intracellular calcium. H2S also relaxes SMC through the release of endothelium- derived hyperpolarizing factor (EDHF) and nitric oxide (NO) from the endothelium. H2S contracts SMC through a reduction in nitric oxide (NO) availability by reacting with NO forming a nitrosothiol compound and through an inhibitory effect on endothelial nitric oxide synthase (eNOS) as well as a reduction in SMC cyclic AMP concentration. Evidence supports a role for H2S in oxygen sensing. Furthermore, reduced endogenous H2S production may also play a role in ischemic heart diseases and hypertension, and treatment with H2S donors and cysteine analogues may be beneficial in treatment of cardiovascular disease. PMID- 22309021 TI - Hemostatic factors as druggable targets in diverse pathologies. PMID- 22309023 TI - Impact of interactions between metal oxides to oxidative reactivity of manganese dioxide. AB - Manganese oxides typically exist as mixtures with other metal oxides in soil water environments; however, information is only available on their redox activity as single oxides. To bridge this gap, we examined three binary oxide mixtures containing MnO(2) and a secondary metal oxide (Al(2)O(3), SiO(2) or TiO(2)). The goal was to understand how these secondary oxides affect the oxidative reactivity of MnO(2). SEM images suggest significant heteroaggregation between Al(2)O(3) and MnO(2) and to a lesser extent between SiO(2)/TiO(2) and MnO(2). Using triclosan and chlorophene as probe compounds, pseudofirst-order kinetic results showed that Al(2)O(3) had the strongest inhibitory effect on MnO(2) reactivity, followed by SiO(2) and then TiO(2). Al(3+) ion or soluble SiO(2) had comparable inhibitory effects as Al(2)O(3) or SiO(2), indicating the dominant inhibitory mechanism was surface complexation/precipitation of Al/Si species on MnO(2) surfaces. TiO(2) inhibited MnO(2) reactivity only when a limited amount of triclosan was present. Due to strong adsorption and slow desorption of triclosan by TiO(2), precursor-complex formation between triclosan and MnO(2) was much slower and likely became the new rate-limiting step (as opposed to electron transfer in all other cases). These mechanisms can also explain the observed adsorption behavior of triclosan by the binary oxide mixtures and single oxides. PMID- 22309024 TI - Chitosan-kaolin coprecipitate as disintegrant in microcrystalline cellulose-based pellets elaborated by extrusion-spheronization. AB - The usefulness of a coprecipitate of chitosan and kaolin as disintegrant in the pellets of microcrystalline cellulose (MCC) and hydrochlorothiazide (HCT) (as a model of poorly water-soluble drug) produced by extrusion-spheronization was evaluated in this study. The effectiveness of chitosan-kaolin coprecipitate to increase the dissolution rate was compared with that of kaolin and chitosan. A possible synergy effect was also evaluated between the coprecipitate, kaolin or chitosan and sorbitol, added to the pellets as a very water-soluble diluent. The chitosan-kaolin coprecipitate, the kaolin or the chitosan allowed pellets to be obtained of adequate size, roundness, mechanical strength and flow properties. Furthermore, the incorporation of chitosan-kaolin coprecipitate or chitosan significantly increased the dissolution rate of HCT independently of the sorbitol content. The effects on the dissolution of HCT derived from the incorporation of coprecipitate to the pellets can be attributed to its content of chitosan. However, the addition of kaolin into the pellets did not significantly affect the HCT dissolution process. The pellets incorporating coprecipitated chitosan-kaolin or chitosan and the maximum proportion of sorbitol (50%) led to the highest HCT dissolution rate and experienced a rapid and complete disintegration in the dissolution medium. PMID- 22309025 TI - Ten-year angiographic result of a large right coronary artery fistula treated percutaneously: many questions remain unanswered. AB - We describe an adult patient with right coronary artery to right atrium fistula, which was treated percutaneously 10 years earlier. His coronary angiogram done presently demonstrated no residual fistula, but there was persistence of aneurysmally dilated proximal right coronary artery segment that gave rise to many unanswered questions regarding management of coronary artery fistulas. We discuss the short- and long-term therapeutic dilemmas in the management of coronary artery fistula. PMID- 22309026 TI - Structural behavior and interactions of dendrimer within lyotropic liquid crystals, monitored by EPR spectroscopy and rheology. AB - Micro- and macrostructural behaviors of three different lyotropic liquid crystals (LLCs) loaded with a dendrimer, namely second generation poly(propylene imine) (PPI-G2), were studied by means of rheology and electron paramagnetic resonance (EPR). The three mesophases were L(alpha), Q(224), and H(II) composed of glycerol monooleate (GMO) and water-PPI-G2 solution (and d-alpha-tocopherol (vitamin E) in the case of H(II)). We characterized the impact of PPI-G2 interactions with the components of the host mesophases on their structural characteristics on different length scales. The incorporation of PPI-G2 within the L(alpha) and H(II) systems induced the formation of more elastic hexagonal systems with a "solidlike" behavior, while in the Q(224) system a different trend with a "liquidlike" behavior was observed. As a result, the dendrimer induced a remarkable change in both the structural and viscoelastic properties of the systems. Hence, the microenvironment in the interface region within the systems was monitored by computer-aided EPR using 5-doxylstearic acid (5-DSA) as a pH dependent probe. The microviscosity (tau) and order (S) of systems were found to be sensitive to the PPI-G2 presence: when PPI-G2 concentration increased, tau and S increased in both the L(alpha) and Q(224) systems. In the H(II) systems two trends were observed, reflecting a decrease in tau and S up to 10 wt % PPI-G2 and subsequently their increase at higher dendrimer concentrations. It was assessed that PPI-G2 interacted strongly with the GMO hydroxyl groups in the L(alpha) phase, with the water molecules in the Q(224) systems. In the H(II) mesophase strong interactions with both the water and GMO hydroxyl molecules were detected. PMID- 22309027 TI - Silylium ion-catalyzed challenging Diels-Alder reactions: the danger of hidden proton catalysis with strong Lewis acids. AB - The pronounced Lewis acidity of tricoordinate silicon cations brings about unusual reactivity in Lewis acid catalysis. The downside of catalysis with strong Lewis acids is, though, that these do have the potential to mediate the formation of protons by various mechanisms, and the thus released Bronsted acid might even outcompete the Lewis acid as the true catalyst. That is an often ignored point. One way of eliminating a hidden proton-catalyzed pathway is to add a proton scavenger. The low-temperature Diels-Alder reactions catalyzed by our ferrocene stabilized silicon cation are such a case where the possibility of proton catalysis must be meticulously examined. Addition of the common hindered base 2,6 di-tert-butylpyridine resulted, however, in slow decomposition along with formation of the corresponding pyridinium ion. Quantitative deprotonation of the silicon cation was observed with more basic (Mes)(3)P to yield the phosphonium ion. A deuterium-labeling experiment verified that the proton is abstracted from the ferrocene backbone. A reasonable mechanism of the proton formation is proposed on the basis of quantum-chemical calculations. This is, admittedly, a particular case but suggests that the use of proton scavengers must be carefully scrutinized, as proton formation might be provoked rather than prevented. Proton catalyzed Diels-Alder reactions are not well-documented in the literature, and a representative survey employing TfOH is included here. The outcome of these catalyses is compared with our silylium ion-catalyzed Diels-Alder reactions, thereby clearly corroborating that hidden Bronsted acid catalysis is not operating with our Lewis acid. Several simple-looking but challenging Diels-Alder reactions with exceptionally rare dienophile/enophile combinations are reported. Another indication is obtained from the chemoselectivity of the catalyses. The silylium ion-catalyzed Diels-Alder reaction is general with regard to the oxidation level of the alpha,beta-unsaturated dienophile (carbonyl and carboxyl), whereas proton catalysis is limited to carbonyl compounds. PMID- 22309028 TI - Culture and the body: East-West differences in visceral perception. AB - This research investigated cross-cultural differences in the accuracy of individuals' perceptions of internal visceral states. We conducted 4 studies to test the hypothesis that Asians are less sensitive to internal physiological cues relative to European Americans. Studies 1 and 2 assessed cultural differences in visceral perception via tests of misattributions of arousal: Study 1 involved false heart rate feedback during an emotionally evocative slideshow and examined subsequent self-reported affective changes; Study 2 manipulated apparent physiological arousal and measured its effects on attraction via an immersive virtual environment. Study 3 directly assessed visceral perception using a heartbeat detection task. All 3 studies found Asians to be less viscerally perceptive than European Americans. Study 4 examined one possible cultural mechanism for the observed difference and found evidence for contextual dependency as a mediator of the culture-visceral perception link. PMID- 22309029 TI - Is there a hierarchy of social inferences? The likelihood and speed of inferring intentionality, mind, and personality. AB - People interpret behavior by making inferences about agents' intentionality, mind, and personality. Past research studied such inferences 1 at a time; in real life, people make these inferences simultaneously. The present studies therefore examined whether 4 major inferences (intentionality, desire, belief, and personality), elicited simultaneously in response to an observed behavior, might be ordered in a hierarchy of likelihood and speed. To achieve generalizability, the studies included a wide range of stimulus behaviors, presented them verbally and as dynamic videos, and assessed inferences both in a retrieval paradigm (measuring the likelihood and speed of accessing inferences immediately after they were made) and in an online processing paradigm (measuring the speed of forming inferences during behavior observation). Five studies provide evidence for a hierarchy of social inferences-from intentionality and desire to belief to personality-that is stable across verbal and visual presentations and that parallels the order found in developmental and primate research. PMID- 22309030 TI - Melon RNA interference (RNAi) lines silenced for Cm-eIF4E show broad virus resistance. AB - Efficient and sustainable control of plant viruses may be achieved using genetically resistant crop varieties, although resistance genes are not always available for each pathogen; in this regard, the identification of new genes that are able to confer broad-spectrum and durable resistance is highly desirable. Recently, the cloning and characterization of recessive resistance genes from different plant species has pointed towards eukaryotic translation initiation factors (eIF) of the 4E family as factors required for the multiplication of many different viruses. Thus, we hypothesized that eIF4E may control the susceptibility of melon (Cucumis melo L.) to a broad range of viruses. To test this hypothesis, Cm-eIF4E knockdown melon plants were generated by the transformation of explants with a construct that was designed to induce the silencing of this gene, and the plants from T2 generations were genetically and phenotypically characterized. In transformed plants, Cm-eIF4E was specifically silenced, as identified by the decreased accumulation of Cm-eIF4E mRNA and the appearance of small interfering RNAs derived from the transgene, whereas the Cm eIF(iso)4E mRNA levels remained unaffected. We challenged these transgenic melon plants with eight agronomically important melon-infecting viruses, and identified that they were resistant to Cucumber vein yellowing virus (CVYV), Melon necrotic spot virus (MNSV), Moroccan watermelon mosaic virus (MWMV) and Zucchini yellow mosaic virus (ZYMV), indicating that Cm-eIF4E controls melon susceptibility to these four viruses. Therefore, Cm-eIF4E is an efficient target for the identification of new resistance alleles able to confer broad-spectrum virus resistance in melon. PMID- 22309031 TI - Serum soluble interleukin 2 receptor (sIL-2R) as a marker of acute rejection in renal transplant children. AB - The aim of the study was to evaluate whether or not serum levels of soluble interleukin 2 receptor (sIL-2R) predict acute rejection in pediatric recipients. We studied 51 pediatric renal transplant recipients divided into three groups: Group 1) Biopsy-proven cellular acute rejection (n = 19), Group 2) Graft dysfunction with histological diagnosis other than acute rejection (n = 8) and Group 3) Patients with stable graft function, no biopsy (n = 24). Serum samples for sIL-2R measurement by sandwich ELISA were obtained at the time of renal transplant and at the time of renal biopsy due to graft dysfunction (Groups 1 and 2) or at six months post-transplant in the case of Group 3. The mean +/- s.e. serum values of sIL-2R were higher in patients during acute rejection (6539 +/- 1802 pg/mL) compared to patients with other causes of graft dysfunction (2217 +/- 256 pg/mL) or stable graft function at six months (2183 +/- 283 pg/mL) (Kruskal Wallis p = 0.004). When the sIL2-R levels at the time of transplant were compared to those at the time of biopsy (Groups 1 and 2) or at six months post-transplant in Group 3, there was no significant difference between baseline and biopsy in the acute rejection group (paired t-test = 0.07), whereas there was a significant reduction in Groups 2 and 3. PMID- 22309032 TI - Heterogeneous reactions of epoxides in acidic media. AB - Epoxides have recently been identified as important intermediates in the gas phase oxidation of hydrocarbons, and their hydrolysis products have been observed in ambient aerosols. To evaluate the role of epoxides in the formation of secondary organic aerosols (SOA), the kinetics and mechanism of heterogeneous reactions of two model epoxides, isoprene oxide and alpha-pinene oxide, with sulfuric acid, ammonium bisulfate, and ammonium sulfate have been investigated using complementary experimental techniques. Kinetic experiments using a fast flow reactor coupled to an ion drift-chemical ionization mass spectrometer (ID CIMS) show a fast irreversible loss of the epoxides with the uptake coefficients (gamma) of (1.7 +/- 0.1) * 10(-2) and (4.6 +/- 0.3) * 10(-2) for isoprene oxide and alpha-pinene oxide, respectively, for 90 wt % H(2)SO(4) and at room temperature. Experiments using attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) reveal that diols are the major products in ammonium bisulfate and dilute H(2)SO(4) (<25 wt %) solutions for both epoxides. In concentrated H(2)SO(4) (>65 wt %), acetals are formed from isoprene oxide, whereas organosulfates are produced from alpha-pinene oxide. The reaction of the epoxides with ammonium sulfate is slow and no products are observed. The epoxide reactions using bulk samples and Nuclear Magnetic Resonance (NMR) spectroscopy reveal the presence of diols as the major products for isoprene oxide, accompanied by aldehyde formation. For alpha-pinene oxide, organosulfate formation is observed with a yield increasing with the acidity. Large yields of organosulfates in all NMR experiments with alpha-pinene oxide are attributed to the kinetic isotope effect (KIE) from the use of deuterated sulfuric acid and water. Our results suggest that acid-catalyzed hydrolysis of epoxides results in the formation of a wide range of products, and some of the products have low volatility and contribute to SOA growth under ambient conditions prevailing in the urban atmosphere. PMID- 22309033 TI - Effects of resveratrol on the amelioration of insulin resistance in KKAy mice. AB - Resveratrol (Res) has attracted great interest regarding its effects related to metabolic syndrome, especially for lipid metabolic disorder or insulin resistance; however, the underlying mechanisms remain elusive. To explore the effects of Res on insulin sensitivity and the underlying mechanism, insulin resistant KKA(y) mice were treated with 2 and 4 g/kg diets of Res for 12 weeks. After the treatment, blood glucose, serum insulin, glucose tolerance, and insulin tolerance, as well as other indices such as adiponectin mRNA in epididymal adipose tissues, silent information regulator 1 (Sirt1), AMP-activated protein kinase (AMPK), insulin receptor substrate 1 (IRS1), and phosphorylated protein kinase B (PKB/AKT) proteins in liver and soleus muscles, were investigated. The results indicate that Res intervention reduces blood glucose and serum insulin levels, improves insulin and glucose tolerance, increases serum adiponectin and adiponectin mRNA levels in epididymal adipose tissues, and more importantly, elevates Sirt1, p-AMPK, p-IRS1, and p-AKT levels in liver and soleus muscles. In conclusion, Res could improve insulin sensitivity and ameliorate insulin resistance in KKA(y) mice, which may be associated with the upregulation of Sirt1 protein in liver and soleus muscles and consequent AMPK activation, as well as insulin-signaling related proteins. PMID- 22309034 TI - Transjugular intrahepatic portosystemic shunt following liver transplantation: can outcomes be predicted? AB - Transjugular intrahepatic portosystemic shunt (TIPS) has been fairly effective in managing portal hypertension in the setting of cirrhosis. The aim is to study the safety and efficacy of TIPS in liver transplant (LT) recipients. Fifteen patients underwent TIPS insertion following LT. Indications were refractory ascites (12), hepatic hydrothorax (2), and bleeding esophageal varices (1). Seven patients (46.6%) had complete (C) resolution of ascites, while eight (53.4%) had partial or no (PN) resolution. Portal pressure and portal-right atrial pressure gradients post-TIPS were comparable. Ammonia levels were significantly higher in the PN group. Encephalopathy occurred in two patients (PN group). Four patients required re-transplantation and seven patients expired. The five-yr survival probability was 60.0% for the C group and 66.7% for the PN group. Currently, six patients are alive without clinical evidence of ascites. Two patients are alive but require re transplantation. TIPS is a safe and effective method to control refractory ascites after LT. Portal pressure changes did not seem to correlate with resolution of ascites. Earlier allograft dysfunction is more likely with PN resolution of ascites after TIPS, and thus early re-transplantation should be considered. Re-transplantation in the context of organ dysfunction and graft failure should be a priority when considering TIPS. PMID- 22309035 TI - Delivery of small interfering RNA by peptide-targeted mesoporous silica nanoparticle-supported lipid bilayers. AB - The therapeutic potential of small interfering RNAs (siRNAs) is severely limited by the availability of delivery platforms that protect siRNA from degradation, deliver it to the target cell with high specificity and efficiency, and promote its endosomal escape and cytosolic dispersion. Here we report that mesoporous silica nanoparticle-supported lipid bilayers (or "protocells") exhibit multiple properties that overcome many of the limitations of existing delivery platforms. Protocells have a 10- to 100-fold greater capacity for siRNA than corresponding lipid nanoparticles and are markedly more stable when incubated under physiological conditions. Protocells loaded with a cocktail of siRNAs bind to cells in a manner dependent on the presence of an appropriate targeting peptide and, through an endocytic pathway followed by endosomal disruption, promote delivery of the silencing nucleotides to the cytoplasm. The expression of each of the genes targeted by the siRNAs was shown to be repressed at the protein level, resulting in a potent induction of growth arrest and apoptosis. Incubation of control cells that lack expression of the antigen recognized by the targeting peptide with siRNA-loaded protocells induced neither repression of protein expression nor apoptosis, indicating the precise specificity of cytotoxic activity. In terms of loading capacity, targeting capabilities, and potency of action, protocells provide unique attributes as a delivery platform for therapeutic oligonucleotides. PMID- 22309038 TI - Possible association between OPRM1 genetic variance at the 118 locus and alcohol dependence in a large treatment sample: relationship to alcohol dependence symptoms. AB - BACKGROUND: Several lines of evidence from previous research indicate that opioid receptors play an important role in ethanol reinforcement and alcohol dependence (AD) risk. Conflicting results were reported on the role of the mu-opioid receptor (OPRM1) polymorphism A118G (Asn40Asp, rs1799971) in the development of alcoholism. METHODS: We investigated a total number of 1,845 alcohol-dependent subjects recruited from inpatient facilities in Germany and 1,863 controls for the mu-opioid receptor (OPRM1) polymorphism using chi-square statistics. RESULTS: An association between the OPRM variant and AD was detected (p = 0.022), in recessive (AA vs. GA/GG) and co-dominant (AA vs. GA) models of inheritance. An association between the OPRM variant and the DSM-IV criterion "efforts to cut down or could not" (p = 0.047) was found, but this did not remain significant after the correction for multiple testing. CONCLUSIONS: The results indicate that this functional OPRM variant is associated with risk of AD and these findings apply to more severe AD, although the association is only nominally significant. PMID- 22309039 TI - A case report of multiple Eccrine hydrocystomas successfully treated with subdermal 1,444-nm micropulsed neodymium-doped yttrium aluminum garnet laser. PMID- 22309040 TI - Current knowledge and tomorrows challenges of breast, ovarian and prostate cancer genetics. PMID- 22309041 TI - Holmes heart--a simple antenatal diagnosis of a complex cardiac anomaly? Fetal echocardiographic findings and review. AB - Double inlet left ventricle as a rare cardiac malformation comprises a broad spectrum of anatomic variants making its correct antenatal diagnosis challenging. We report on echocardiographic findings of three fetuses found to have a less frequent morphologic subgroup of double inlet left ventricle, namely Holmes heart, characterized by a single (left) ventricle connected to both atrioventricular orifices and normally related arteries. We addressed the pre- and perinatal management as well as additional abnormalities and discussed our experiences together with what is known from current literature. PMID- 22309042 TI - Mixed ionic liquids: the case of pyridinium-based fluids. AB - We report in this work a combined experimental and computational study on the molecular level structuring of binary ionic liquid mixtures comprising pyridium cations. The effect of anions on liquid structure was analyzed from the mixing (mixture 1) of [b3mpy][BF(4)] and [b3mpy][N(CN)(2)] ionic liquids, in the full composition range, leading to [b3mpy][BF(4)](x)[N(CN)(2)](1-x) mixed ionic liquids. The effect of the length of alkylic chains in cations was studied with mixtures (mixture 2) of [b3mpy][BF(4)] and [o3mpy][BF(4)] ionic liquids, also studied in the full composition range, leading to [b3mpy](x)[o3mpy](1-x)[BF(4)] ionic liquids. Fourier transform infrared-attenuated total reflection spectra were recorded and analyzed as a function of anionic and cationic composition for the two studied mixture types. Classical molecular dynamics simulations were also performed for mixtures 1 and 2 as a function of anionic and cationic composition. The reported experimental and computational results show that the properties of the studied mixed systems change in an almost linear way, leading to almost ideal mixtures from the thermodynamic viewpoint, and thus pointing to simple dilution effects of the involved ions controlling the mixture properties. PMID- 22309044 TI - Antimony (Sb) and arsenic (As) in Sb mining impacted paddy soil from Xikuangshan, China: differences in mechanisms controlling soil sequestration and uptake in rice. AB - Foods produced on soils impacted by antimony (Sb) mining activities are a potential health risk due to plant uptake of the contaminant metalloids (Sb) and arsenic (As). Here we report for the first time the chemical speciation of Sb in soil and porewater of flooded paddy soil, impacted by active Sb mining, and its effect on uptake and speciation in rice plants (Oryza sativa L. cv Jiahua). Results are compared with behavior and uptake of As. Pot experiments were conducted under controlled conditions in a climate chamber over a period of 50 days. In pots without rice plants, flooding increased both the concentration of dissolved Sb (up to ca. 2000 MUg L(-1)) and As (up to ca. 1500 MUg L(-1)). When rice was present, Fe plaque developing on rice roots acted as a scavenger for both As and Sb, whereby the concentration of As, but not Sb, in porewater decreased substantially. Dissolved Sb in porewater, which occurred mainly as Sb(V), correlated with Ca, indicating a solubility governed by Ca antimonate. No significant differences in bioaccumulation factor and translocation factor between Sb and As were observed. Greater relative concentration of Sb(V) was found in rice shoots compared to rice root and porewater, indicating either a preferred uptake of Sb(V) or possibly an oxidation of Sb(III) to Sb(V) in shoots. Adding soil amendments (olivine, hematite) to the paddy soil had no effect on Sb and As concentrations in porewater. PMID- 22309045 TI - Rapid-onset heparin-induced thrombocytopenia without previous heparin exposure. AB - Heparin-induced thrombocytopenia (HIT) is one of the most common immune-mediated drug reactions. Immunoglobulin G-type antibodies against platelet factor 4(PF4)/heparin complexes are known to play a key role in the pathogenesis of HIT. Rapid-onset HIT is caused by the presence of circulating HIT antibodies at the time of heparin readministration. These antibodies are generally resulted from a recent immunizing exposure to heparin. Here we report a case of rapid-onset HIT developed after a septicemia without previous heparin exposure. The diagnosis of HIT as well as the presence of platelet activating and heparin-dependent antibodies was confirmed by ELISA and flow cytometric functional assays. Our case report reinforces that rapid-onset HIT cannot be excluded only based on the absence of previous heparin exposure. In addition, it may support the new theory of pre-immunization by PF4-coated bacteria in the pathomechanism of HIT. We also call the attention that venous limb gangrene can be rarely associated with HIT and thrombosis even in the absence of coumarin therapy. Furthermore, transient presence of anti-phospholipid antibodies can cause a differential diagnostic problem in the cases of HIT. PMID- 22309046 TI - Pharmacodynamic effects of clopidogrel in pediatric cardiac patients: a comparative study of platelet aggregation response. AB - Little data on pediatric percent platelet aggregation (%PA) exist in the literature, particularly in cardiac patients and in response to clopidogrel. The objectives were to estimate the %PA range expected in pediatric patients and to measure the clopidogrel effect on %PA in the PICOLO (Platelet Inhibition in Children on Clopidogrel) trial. To estimate a neonatal/infant %PA response range, %PA induced by 5 uM adenosine diphosphate (ADP) was assessed using light transmission aggregometry in 16 cord and 11 normal adult blood samples and prior to clopidogrel therapy in 49 neonatal and 49 infant/toddler cardiac patients enrolled in PICOLO. The %PA induced by 5 uM thrombin receptor-activating peptide (TRAP) was also assessed for 10 neonates and 21 infants/toddlers enrolled in PICOLO and compared with 11 adult samples. Percent inhibition of platelet aggregation (%IPA) induced by 5 uM ADP at steady-state clopidogrel levels was assessed in 33 neonates and 39 infants/toddlers. ADP-induced %PA was lowest in cord blood samples, intermediate in study neonates and infants/toddlers, and highest in adults. Similarly, TRAP-induced platelet aggregation was lower in neonates and infants/toddlers than adults. For all groups, %PA and %IPA were highly variable, with 11% of neonates and 13% of infants/toddlers showing <10% IPA. In conclusion, ADP- and TRAP-induced %PA is lower in pediatric cardiac patients than normal adults, but highly variable in both. The lower baseline %PA may explain why the pediatric clopidogrel dose providing 30-50% IPA (0.20 mg/kg/day) is lower than a simple weight-based extrapolation of the adult dose (75 mg/day) providing similar inhibition. PMID- 22309047 TI - Measurement of platelet responsiveness using antibody-coated magnetic beads for lab-on-a-chip applications. AB - We investigate novel methods for the quantification of platelet responsiveness that are suited for implementation in lab-on-a-chip devices. Magnetic beads are convenient carriers for rapid capture and manipulation of biological cells in a miniaturized system. In this article, we demonstrate that antibody-coated magnetic beads can be used to quantify platelet responsiveness. We use anti-CD62P coated beads to capture activated platelets from samples stimulated with a PAR-1 specific agonist SFLLRN, also known as thrombin receptor activator peptide. The responsiveness of the platelets is analyzed via the remaining unbound platelets in the solution and compared to a reference method in which the number of activated platelets is analyzed via fluorescent labeling. The effective concentrations for platelet activation are in agreement for the two assay types, proving that platelet responsiveness can be quantified using antibody-coated magnetic beads. We discuss the outlook for application in lab-on-a-chip devices. PMID- 22309048 TI - Effects of FEIBA on platelet and leucocyte activation in severe haemophilia patients with inhibitors. AB - Factor eight inhibitory bypassing agent (FEIBA) is used as a therapeutic option in haemophilia patients who have developed inhibitors. The measurement of thrombin generation has been applied to monitor the efficacy of FEIBA. However, a major concern about the clinical use of FEIBA is whether or not an increase in thrombin activity causes subsequent platelet activation and risk of thrombosis. Our aim is to evaluate whether FEIBA causes platelet and leucocyte activation in haemophilia patients with inhibitors. We evaluated the effects of FEIBA on platelet and leucocyte activity in correlation with thrombin generation. Initially, an in vitro study was conducted to evaluate the effects of FEIBA on platelet and leucocyte activity (using flow cytometry) using peripheral blood from normal volunteers. We then performed an ex vivo study looking at the effect of FEIBA on the above parameters in two haemophiliacs with high-titre inhibitors. A parallel study was also carried out ex vivo to evaluate thrombin generation using a thrombinoscope. FEIBA did not cause platelet or leucocyte activation in either the in vitro or ex vivo studies but showed a predictable increase in thrombin generation. Our study is the first one to address the effect of FEIBA on platelet and leucocyte function. We found no evidence of 'systemic' platelet activation. The findings suggest that whilst FEIBA improves global haemostasis, platelet activation is likely to be contained to the site of injury and systemic platelet activation, a previously feared consequence of FEIBA infusion that that may have contributed to thrombotic risk is absent. PMID- 22309049 TI - Mechanism of anti-platelet activity of Oligoporus tephroleucus oligoporin A: involvement of extracellular signal-regulated kinase phosphorylation and cyclic nucleotide elevation. AB - This study investigated the inhibitory effects of oligoporin A on platelet aggregation and the mechanism of its action on downstream signaling molecules. Oligoporin A was isolated from the fruiting bodies of Oligoporus tephroleucus (Polyporaceae). The anti-platelet activities of oligoporin A were studied using rat platelets. The effects of oligoporin A on intracellular Ca(2+) mobilization, ATP release, production of the cyclic nucleotides cAMP and cGMP, extracellular signal-regulated kinase (ERK) 2 phosphorylation, and fibrinogen binding to active integrin alpha(II)(b)beta(3) were assessed. Oligoporin A, but not oligoporins B and C, inhibited collagen-induced platelet aggregation in a concentration dependent manner. Interestingly, oligoporin A did not affect ADP- and thrombin induced platelet aggregations, which act on different types of membrane receptors. Granule secretion analysis demonstrated that oligoporin A significantly and dose-dependently reduced collagen-induced ATP release and intracellular Ca(2+) mobilization. Additionally, oligoporin A induced the dynamic increase in cAMP and cGMP. Increased cGMP production was further confirmed by the simultaneous production of nitric oxide. Pretreatment with oligoporin A significantly blocked collagen-induced ERK2 phosphorylation. Finally, oligoporin A vaguely diminished the binding of fibrinogen to its cognate receptor, integrin alpha(II)(b)beta(3). The results indicate that oligoporin A inhibits only collagen-induced platelet aggregation mediated through the modulation of downstream signaling molecules. Oligoporin A may be beneficial against cardiovascular disease provoked by aberrant platelet activation. PMID- 22309051 TI - The evolution of novel animal signals: silk decorations as a model system. AB - Contemporary animal signals may derive from an elaboration of existing forms or novel non-signalling traits. Unravelling the evolution of the latter is challenging because experiments investigating the maintenance of the signal may provide little insight into its early evolution. The web decorations, or stabilimenta of some orb web spiders represent an intriguing model system to investigate novel animal signals. For over 100 years, biologists have struggled to explain why spiders decorate their webs with additional threads of silk, producing a conspicuous signal on a construction whose function is to entangle unsuspecting prey. The numerous explanations for the maintenance of this behaviour starkly contrast with the absence of a plausible explanation for its evolutionary origin. Our review highlights the difficulties in resolving both the evolution and maintenance of animal signalling, and inferring the causative arrow even from experimental studies. Drawing on recent research that focuses on physiological processes, we provide a model of the evolutionary progression of web-decorating behaviour. PMID- 22309052 TI - An investigation of a cognitive refocusing technique to improve sleep. AB - Developing techniques designed to minimize arousing cognitions during the evening may be important to help improve the treatment of insomnia. This investigation assessed an intervention that focused exclusively on enhancing cognitive refocusing at sleep onset to change the content and style of presleep cognitions in order to improve sleep. Individuals with primary insomnia (N=10; 90% male, mean age=49.2, SD=12.6) attended four weekly individual meetings. Sleep quality (the Pittsburgh Sleep Quality Index), insomnia severity (the Insomnia Severity Index), sleep parameters based on one week of sleep diaries, and arousing thought content, were compared at baseline, posttreatment, and at a 1-month follow-up. Adherence was high, and participants showed good ability to engage in the procedure. Significant improvements in sleep quality, insomnia severity, sleep onset latency, total sleep time, and arousing thought content were revealed. Large effect sizes were observed on the majority of sleep variables at follow-up. Preliminary results were encouraging regarding a technique that targets the refocusing of thoughts during the evening in order to improve sleep. Further study regarding the efficacy of this procedure is warranted. PMID- 22309053 TI - Early and selective impairments in axonal transport kinetics of synaptic cargoes induced by soluble amyloid beta-protein oligomers. AB - The downstream targets of amyloid beta (Abeta)-oligomers remain elusive. One hypothesis is that Abeta-oligomers interrupt axonal transport. Although previous studies have demonstrated Abeta-induced transport blockade, early effects of low n soluble Abeta-oligomers on axonal transport remain unclear. Furthermore, the cargo selectivity for such deficits (if any) or the specific effects of Abeta on the motility kinetics of transported cargoes are also unknown. Toward this, we visualized axonal transport of vesicles in cultured hippocampal neurons treated with picomolar (pm) levels of cell-derived soluble Abeta-oligomers. We examined select cargoes thought to move as distinct organelles and established imaging parameters that allow organelle tracking with consistency and high fidelity - analyzing all data in a blinded fashion. Abeta-oligomers induced early and selective diminutions in velocities of synaptic cargoes but had no effect on mitochondrial motility, contrary to previous reports. These changes were N-methyl D-aspartate receptor/glycogen synthase kinase-3beta dependent and reversible upon washout of the oligomers. Cluster-mode analyses reveal selective attenuations in faster-moving synaptic vesicles, suggesting possible decreases in cargo/motor associations, and biochemical experiments implicate tau phosphorylation in the process. Collectively, the data provide a biological basis for Abeta-induced axonal transport deficits. PMID- 22309054 TI - Theoretical investigation of water gas shift reaction catalyzed by iron group carbonyl complexes M(CO)5 (M = Fe, Ru, Os). AB - We have investigated the mechanism of M(CO)(5) (M = Fe, Ru, Os) catalyzed water gas shift reaction (WGSR) by using density functional theory and ab initio calculations. Our calculation results indicate that the whole reaction cycle consists of six steps: 1 -> 2 -> 3 -> 4 -> 5 -> 6 -> 2. In this stepwise mechanism the metals Fe, Ru, and Os behave generally in a similar way. However, crucial differences appear in steps 3 -> 4 -> 5 which involve dihydride M(H)(2)(CO)(3)COOH(-) (4') and/or dihydrogen complex MH(2)(CO)(3)COOH(-) (4). The stability of the dihydrogen complexes becomes weaker down the iron group. The dihydrogen complex 4_Fe is only 11.1 kJ/mol less stable than its dihydride 4'_Fe at the B3LYP/II(f)++//B3LYP/II(f) level. Due to very low energy barrier it is very easy to realize the transform from 4_Fe to 4'_Fe and vice versa, and thus for Fe there is no substantial difference to differentiate 4 and 4' for the reaction cycle. The most possible key intermediate 4'_Ru is 38.2 kJ/mol more stable than 4_Ru. However, the barrier for the conversion 3_Ru -> 4'_Ru is 23.8 kJ/mol higher than that for 3_Ru -> 4_Ru. Additionally, 4'_Ru has to go through 4_Ru to complete dehydrogenation 4'_Ru -> 5_Ru. The concerted mechanism 4'_Ru -> 6_Ru, in which the CO group attacks ruthenium while H(2) dissociates, can be excluded. In contrast to Fe and Ru, the dihydrogen complex of Os is too unstable to exist at the level of theory. Moreover, we predict Fe and Ru species are more favorable than Os species for the WGSR, because the energy barriers for the 4 -> 5 processes of Fe and Ru are only 38.9 and 16.2 kJ/mol, respectively, whereas 140.5 kJ/mol is calculated for the conversion 4' -> 5 of Os, which is significantly higher. In general, the calculations are in good agreement with available experimental data. We hope that our work will be beneficial to the development and design of the WGSR catalyst with high performance. PMID- 22309055 TI - Carbon disulfide assisted polymerization of benzene. AB - The chemical transformation of benzene (C(6)H(6)) and carbon disulfide (CS(2)) binary solution under high pressure condition is investigated by means of Raman spectroscopy up to 6.8 GPa. On increasing the pressure, all the Raman bands of benzene decrease in intensity, whereas new broad bands start to be observed at 1520 and 1450 cm(-1), indicating that a highly cross-linked polymer is formed. The recovered sample is analyzed through Raman and FT-IR spectroscopy and is identified as a saturated hydrocarbon and element sulfur. PMID- 22309056 TI - Life cycle inventory and carbon and water FoodPrint of fruits and vegetables: application to a Swiss retailer. AB - Food production and consumption is known to have significant environmental impacts. In the present work, the life cycle assessment methodology is used for the environmental assessment of an assortment of 34 fruits and vegetables of a large Swiss retailer, with the aim of providing environmental decision-support to the retailer and establishing life cycle inventories (LCI) also applicable to other case studies. The LCI includes, among others, seedling production, farm machinery use, fuels for the heating of greenhouses, irrigation, fertilizers, pesticides, storage and transport to and within Switzerland. The results show that the largest reduction of environmental impacts can be achieved by consuming seasonal fruits and vegetables, followed by reduction of transport by airplane. Sourcing fruits and vegetables locally is only a good strategy to reduce the carbon footprint if no greenhouse heating with fossil fuels is involved. The impact of water consumption depends on the location of agricultural production. For some crops a trade-off between the carbon footprint and the induced water stress is observed. The results were used by the retailer to support the purchasing decisions and improve the supply chain management. PMID- 22309058 TI - Consequences of early chilling stress in two Triticum species: plastic responses and adaptive significance. AB - Phenotypic plasticity of two primitive wheat species (Triticum monococcum L. and Triticum dicoccum S.) was studied in response to early chilling stress. Selection pressure differentials, gradients and plasticity costs on plant morphogenesis, growth and reserve carbohydrate consumption were estimated. Regression analysis was applied to investigate differential developmental changes and patterns between treatments. Four-day-old seedlings of T. monococcum and T. dicoccum, differing in plant stature and reserve carbohydrates, were given an early chilling temperature (4 degrees C for 42 day) and compared with control plants grown at 23 degrees C. Early chilling stress resulted in a significant increase in leaf mass ratio (LMR) and relative growth rate (RGR), a reduction in flag leaf size, total biomass, specific leaf area (SLA) and reserve carbohydrate storage at flowering, together with advanced onset of flowering. Selection pressure within the early chilling environment favoured early flowering, smaller SLA, higher LMR and lower reserve carbohydrates, suggesting the observed responses were adaptive. Furthermore, a regression of daily cumulative plant biomass derived from a crop growth simulation model (CERES-Wheat) on crop vegetation period revealed a divergent developmental pattern in early-chilled plants. Using selection pressure gradient analysis, we found similar responses among these traits, except for SLA and sucrose, indicating that these two traits have indirect effects on fitness. Thus, the total effects of SLA and reserve sucrose on relative fitness seem to be buffered via the rapid growth rate in chilled plants. While lower SLA may reduce early chilling stress effects at an individual leaf level, a higher LMR and use of reserve carbohydrates indicated that compensatory growth of chilled plants during the recovery period relied on the concerted action of altered resource allocation and reserve carbohydrate consumption. However, a significant cost of plasticity was evident only for flowering time, LMR and fructan levels in the early chilling environment. Our results demonstrate that morphological and intrinsic developmental (ontogenetic) patterns in two Triticum species respond to early chilling stress. PMID- 22309059 TI - An eye movement analysis of the spatial contiguity effect in multimedia learning. AB - In three studies, eye movements of participants were recorded while they viewed a single-slide multimedia presentation about how car brakes work. Some of the participants saw an integrated presentation in which each segment of words was presented near its corresponding area of the diagram (integrated group, Experiments 1 and 3) or an integrated presentation that also included additional labels identifying each part (integrated-with-labels group, Experiment 2), whereas others saw a separated presentation in which the words were presented as a paragraph below the diagrams (separated group, Experiments 1 and 2) or as a legend below the diagrams (legend group, Experiment 3). On measures of cognitive processing during learning, the integrated groups made significantly more eye movements from text to diagram and vice versa (integrative transitions; d = 1.65 in Experiment 1, d = 0.85 in Experiment 2, and d = 1.44 in Experiment 3) and significantly more eye-movements from the text to the corresponding part of the diagram (corresponding transitions; d = 2.02 in Experiment 1 and d = 1.35 in Experiment 3) than the separated groups. On measures of learning outcome the integrated groups significantly outperformed the separated groups on transfer test score in Experiment 1(d = .80) and Experiment 2 (d = .73) but not in Experiment 3 (d = .35). Spatial contiguity encourages more attempts to integrate words and pictures and enables more successful integration of words and pictures during learning, which can result in meaningful learning outcomes. PMID- 22309060 TI - The 'ToyBox-study' obesity prevention programme in early childhood: an introduction. PMID- 22309061 TI - A systematic approach for the development of a kindergarten-based intervention for the prevention of obesity in preschool age children: the ToyBox-study. AB - The increasing childhood obesity epidemic calls for appropriate measures and effective policies to be applied early in life. Large-scale socioecological frameworks providing a holistic multifactorial and cost-effective approach necessary to support obesity prevention initiatives in this age are however currently missing. To address this missing link, ToyBox-study aims to build and evaluate a cost-effective kindergarten-based, family-involved intervention scheme to prevent obesity in early childhood, which could potentially be expanded on a pan-European scale. A multidisciplinary team of researchers from 10 countries have joined forces and will work to realize this according to a systematic stepwise approach that combines the use of the PRECEDE-PROCEED model and intervention mapping protocol. ToyBox-study will conduct systematic and narrative reviews, secondary data analyses, focus group research and societal assessment to design, implement and evaluate outcome, impact, process and cost effectiveness of the intervention. This is the first time that such a holistic approach has been used on a pan-European scale to promote healthy weight and healthy energy balance related behaviours for the prevention of early childhood obesity. The results of ToyBox-study will be disseminated among key stakeholders including researchers, policy makers, practitioners and the general population. PMID- 22309062 TI - Correlates of energy balance-related behaviours in preschool children: a systematic review. AB - Childhood overweight is a multifactorial health problem influenced by several factors. The interaction of behaviours such as physical activity, sedentary behaviour and eating behaviour determines whether or not a positive energy balance or weight gain is experienced. Knowing the correlates of these behaviours in 4- to 6-year-old children is of major interest for intervention development. According to the systematic literature search, attending a rural preschool was positively associated with physical activity. Gender, age and socioeconomic status were not associated with physical activity, while an indeterminate result was found for ethnicity. Gender and ethnicity were not associated with sedentary behaviour and indeterminate results were found for age and socioeconomic status. Preschoolers were more physically active as well as sedentary on weekdays. Watching television was associated with a higher consumption of snacks and sweet beverages. Strategies aiming to influence energy balance-related behaviours in preschoolers should target both boys and girls and all ethnic groups from low as well as high social status. During the week, there should be a focus on decreasing sedentary behaviour and in the weekend on increasing physical activity. Focusing on television viewing and the consumption of snacks and sweet beverages could/should also be a strategy. PMID- 22309063 TI - Weight status of European preschool children and associations with family demographics and energy balance-related behaviours: a pooled analysis of six European studies. AB - This study aimed to (i) gain insight in the prevalence of overweight indices in European preschoolers (4-7 years); (ii) identify energy balance-related behaviours associated with overweight/obesity; and (iii) identify children at risk for overweight/obesity. Secondary analyses of six European data sets were conducted according to standardized protocols. Based on objectively measured height and weight, prevalence of overweight and obesity across the countries ranged from 8% to 30% and 1% to 13%, respectively, with highest rates in Southern European countries (i.e. Spain and Greece). Positive associations between sedentary behaviours and overweight indices were found. Physical activity and dietary behaviours were not associated, possibly because of methodological limitations. Children of parents with high body mass index or low socioeconomic status were at increased risk of overweight/obesity. In conclusion, large differences in prevalence of overweight and obesity among preschoolers across Europe were observed. Future obesity prevention interventions in preschoolers should target screen time giving specific attention to children from overweight and/or low socioeconomic status parents. There is a need for high methodological quality studies, preferably with a long-term prospective design using sensitive, valid and reliable measures of behaviours, assessing whether and which physical activity and dietary behaviours are associated with overweight in preschoolers. PMID- 22309064 TI - Assessment tools of energy balance-related behaviours used in European obesity prevention strategies: review of studies during preschool. AB - Valid and reliable measures of energy balance-related behaviours are required when evaluating the effectiveness of public health interventions aiming at prevention of childhood obesity. A structured descriptive review was performed to appraise food intake, physical activity and sedentary behaviour assessment tools used in obesity intervention strategies targeting mainly preschool children across Europe. In total, 25 papers are described, addressing energy balance related behaviours as study outcomes and targeting individuals or clusters of individuals at school- or home-based environment. Parentally reported food records and 24-h recalls were commonly used to assess food intake. Subjective levels of physical activity and sedentary behaviour were commonly accessed via parentally reported questionnaires. Accelerometry was used to obtain objective measures of physical activity. Insufficient evidence of tool evaluation was provided. When feasible, food records and accelerometry are recommended as the most appropriate methods to assess food intake in young children. Sedentary behaviour could be assessed via questionnaires that include key indicators of sedentarism and are able to differentiate individual practices. The choice of methodology for the assessment of specific intervention effects should be equally balanced between required accuracy levels and feasibility, and be guided by the intervention targets. PMID- 22309065 TI - Energy balance-related behaviours associated with overweight and obesity in preschool children: a systematic review of prospective studies. AB - The current review aimed to systematically identify dietary, physical activity and sedentary behaviours in preschool children (4-6 years of age) that are prospectively related to overweight or obesity later in childhood. Prospective studies published between January 1990 and June 2010 were selected from searches in PubMed, EMBASE, PsycINFO, CINAHL and Cochrane Library. Studies examining the prospective association between at least one relevant behaviour measured during preschool period (children aged 4-6 years at baseline) in relation to at least one anthropometric measurement at follow-up (age <18 years) were included. Harvest plots were used to summarize the results and draw conclusions from the evidence. Of the 8,718 retrieved papers, 23 papers reporting on 15 different study samples were included in this review. Strong evidence was found for an inverse association between total physical activity and overweight. Moderate evidence was observed for a positive association between television viewing and overweight. Because of the heterogeneity in the assessed dietary behaviours, insufficient evidence was found for an association between dietary intake or specific dietary behaviours and overweight. These results suggest that interventions aiming to prevent overweight among preschool children should focus on promotion of total physical activity and limitation of screen time and that further research is needed to establish whether and which dietary behaviours are important for obesity prevention in this age group. However, despite the lack of evidence for dietary behaviours from the present review, future interventions may already target specific dietary behaviours that are highly prevalent and for which there a clear rationale as well as preliminary evidence that these behaviours are associated with overweight. PMID- 22309066 TI - Influencing factors of screen time in preschool children: an exploration of parents' perceptions through focus groups in six European countries. AB - Preschoolers already spend significant proportions of their waking hours being sedentary. Screen time (i.e. television/DVD viewing and computer use) has been negatively associated with several health outcomes but interventions aiming to reduce preschoolers' sedentary behaviour are scarce. This study aimed to explore parents' perceptions of their preschool children's screen time. One hundred twenty-two parents of low and medium-high socioeconomic status from six European countries with children between 4 and 6 years old were involved in 24 focus groups. Following a qualitative content analysis, the available information and key findings were centrally analysed. Results showed that children tend to like watching television (TV) and most parents do not express worries about their children's TV viewing time. Education is considered to be the main benefit of watching TV and in general, parents only have informal rules about TV viewing. Computer and active games use are less frequent compared with TV viewing. No univocal results are found about the influence of siblings or friends on children's screen time. Weather conditions and parental habits at home are the most important factors influencing children's screen time. Alternatives for screen activities and information on how to set rules for screen time should be provided to parents to assist them in decreasing their preschool children's screen time. PMID- 22309067 TI - A narrative review of psychological and educational strategies applied to young children's eating behaviours aimed at reducing obesity risk. AB - Strategies to reduce risk of obesity by influencing preschool children's eating behaviour are reviewed. The studies are placed in the context of relevant psychological processes, including inherited and acquired preferences, and behavioural traits, such as food neophobia, 'enjoyment of food' and 'satiety responsiveness'. These are important influences on how children respond to feeding practices, as well as predictors of obesity risk. Nevertheless, in young children, food environment and experience are especially important for establishing eating habits and food preferences. Providing information to parents, or to children, on healthy feeding is insufficient. Acceptance of healthy foods can be encouraged by five to ten repeated tastes. Recent evidence suggests rewarding healthy eating can be successful, even for verbal praise alone, but that palatable foods should not be used as rewards for eating. Intake of healthier foods can be promoted by increasing portion size, especially in the beginning of the meal. Parental strategies of pressuring to eat and restriction do not appear to be causally linked to obesity, but are instead primarily responses to children's eating tendencies and weight. Moderate rather than frequent restriction may improve healthy eating in children. Actively positive social modelling by adults and peers can be effective in encouraging healthier eating. PMID- 22309068 TI - Critical narrative review to identify educational strategies promoting physical activity in preschool. AB - The aim of this narrative review is critically to evaluate educational strategies promoting physical activity that are used in the preschool setting in the context of obesity prevention programmes. Literature search was conducted between April and August 2010 in English and German databases (PubMED, PsychINFO, PSYNDEX, ERIC, FIS Bildung). Outcomes considered were time and intensity of physical activity, motor skills or measures of body composition. A total of 19 studies were included. Ten studies added physical activity lessons into their curriculum, one study provided more time for free play, eight studies focused on the social and play environment. Studies reporting positive outcomes implemented physical activity sessions that lasted at least 30 min d(-1). Several studies showed that children are most active in the first 10-15 min. The existence or installation of playground markings or fixed play equipment had no effect, whereas the presence or addition of portable play equipment was positively correlated with moderate-to vigorous physical activity. Teacher training may be a key element for successful interventions. To overcome time constraints, a suggested solution is to integrate physical activity into daily routines and other areas of the preschool curriculum. PMID- 22309069 TI - Identifying effective behavioural models and behaviour change strategies underpinning preschool- and school-based obesity prevention interventions aimed at 4-6-year-olds: a systematic review. AB - The aim of this comprehensive systematic review was to identify the most effective behavioural models and behaviour change strategies, underpinning preschool- and school-based interventions aimed at preventing obesity in 4-6-year olds. Searching was conducted from April 1995 to April 2010 using MEDLINE, EMBASE, CINAHL, PsycINFO and The Cochrane Library. Epidemiological studies relevant to the research question with controlled assignment of participants were included in the review, if they had follow-up periods of 6 months or longer. Outcomes included markers of weight gain; markers of body composition; physical activity behaviour changes and dietary behaviour changes. Twelve studies were included in the review. The most commonly used model was social cognitive theory (SCT)/social learning theory (SLT) either as a single model or in combination with other behavioural models. Studies that used SCT/SLT in the development of the intervention had significant favourable changes in one, or more, outcome measures. In addition, interventions that (i) combined high levels of parental involvement and interactive school-based learning; (ii) targeted physical activity and dietary change; and (iii) included long-term follow-up, appeared most effective. It is suggested that interventions should also be focused on developing children's (and parents') perceived competence at making dietary and physical changes. PMID- 22309070 TI - Existing policies, regulation, legislation and ongoing health promotion activities related to physical activity and nutrition in pre-primary education settings: an overview. AB - Obesity prevention efforts for school-aged children and adolescents are increasing in number. However, little has been done to address the problem in the preschool age. To address this age group, an evidence-based preschool programme on physical activity (PA) and nutrition is developed within the ToyBox project. Environmental influencing factors such as policies and competitive health promotion activities could inhibit or induce a successful health promotion programme. This paper describes an overview of existing policies, legislation and/or regulations and health promotion activities in the preschool setting. METHOD: data were gathered on policies and activities aiming to improve healthy eating and PA of young children (age group 4-6 years) in Belgium-Flanders, Bulgaria, Germany, Greece, Poland and Spain. A limited number of influencing policies, regulations and/or legislation exists; agenda setting of health promotion and policy evaluations in all relevant policy areas was lacking. Also, health promotion activities in preschool the setting did not exist in all six European countries and high-quality preschool-based health interventions existed in three of the six ToyBox countries. PMID- 22309071 TI - Evidence-based recommendations for the development of obesity prevention programs targeted at preschool children. AB - The ToyBox intervention was developed using an evidence-based approach, using the findings of four reviews. These reviews included three critical and narrative reviews of educational strategies and psychological approaches explaining young children's acquisition and formation of energy-balance related behaviours, and the management of these behaviours, and also a systematic review of behavioural models underpinning school-based interventions in preschool and school settings for the prevention of obesity in children aged 4-6 years. This paper summarises and translates the findings from these reviews into practical evidence based recommendations for researchers and policy-makers to consider when developing and implementing interventions for the prevention of overweight and obesity in young (aged 4-6 years) children. The recommendations focus on two behaviours, physical activity and sedentary behaviour, and healthy eating, and include general recommendations, intervention approaches, interventions content, and simple messages. The review also briefly examines the role that the commercial sector plays in hindering or facilitating attempts to create healthy food environments for children. This paper also recognises that childhood obesity is not an issue for the education sector alone; it needs to be tackled at a multi sectoral level, recognizing the particularly important role of local governments, nongovernment organizations and the media. PMID- 22309072 TI - The novel, orally bioavailable HSP90 inhibitor NVP-HSP990 induces cell cycle arrest and apoptosis in multiple myeloma cells and acts synergistically with melphalan by increased cleavage of caspases. AB - Heat shock protein 90 (HSP90) binds and stabilizes numerous proteins and kinases essential for myeloma cell survival and proliferation. We and others have recently demonstrated that inhibition of HSP90 by small molecular mass inhibitors induces cell death in multiple myeloma (MM). However, some of the HSP90 inhibitors involved in early clinical trials have shown limited antitumor activity and unfavorable toxicity profiles. Here, we analyzed the effects of the novel, orally bioavailable HSP90 inhibitor NVP-HSP990 on MM cell proliferation and survival. The inhibitor led to a significant reduction in myeloma cell viability and induced G2 cell cycle arrest, degradation of caspase-8 and caspase 3, and induction of apoptosis. Inhibition of the HSP90 ATPase activity was accompanied by the degradation of MM phospho-Akt and phospho-ERK1/2 and upregulation of Hsp70. Exposure of MM cells to a combination of NVP-HSP990 and either melphalan or histone deacetylase (HDAC) inhibitors caused synergistic inhibition of viability, increased induction of apoptosis, and was able to overcome the primary resistance of the cell line RPMI-8226 to HSP90 inhibition. Combined incubation with melphalan and NVP-HSP990 led to synergistically increased cleavage of caspase-2, caspase-9, and caspase-3. These data demonstrate promising activity for NVP-HSP990 as single agent or combination treatment in MM and provide a rationale for clinical trials. PMID- 22309073 TI - Anion effects in the scattering of CO2 from the room-temperature ionic liquids [bmim][BF4] and [bmim][Tf2N]: insights from quantum mechanics/molecular mechanics trajectories. AB - Quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations have been carried out to model the scattering of hyperthermal (15 kcal/mol) CO(2) on the surfaces of two common imidazolium based room-temperature ionic liquids (RTILs) [bmim][BF4] and [bmim][Tf2N]. Good agreement was achieved in comparison with experiment. The [bmim][BF4] surface is found to be more absorptive of CO(2) than [bmim][Tf2N], which leads to greater loss in translational energy and less rotational excitation of CO(2)'s that scatter from [bmim][BF4]. These differences are found to result from a interplay of differences in the structure of the interface and the strength of interactions that depend on anion identity. Our results also suggest that CO(2) interacts strongly with ionic species on the RTIL surfaces due to the large induced dipole moments on CO(2) during the collisions. The inclusion of electronic polarization is critical in determining the final rotational excitation of CO(2) compared to results from an MM model with fixed charge. PMID- 22309074 TI - Reproducibility of tactile assessments for children with unilateral cerebral palsy. AB - A systematic review identified tactile assessments used in children with cerebral palsy (CP), but their reproducibility is unknown. Sixteen children with unilateral CP and 31 typically developing children (TDC) were assessed 2-4 weeks apart. Test-retest percent agreements within one point for children with unilateral CP (and TDC) were Semmes-Weinstein monofilaments: 75% (90%); single point localization: 69% (97%); static two-point discrimination: 93% (97%); and moving two-point discrimination: 87% (97%). Test-retest reliability for registration and unilateral spatial tactile perception tests was high in children with CP (intraclass correlation coefficient [ICC] = 0.79-0.96). Two tests demonstrated a learning effect for children with CP, double simultaneous and tactile texture perception. Stereognosis had a ceiling effect for TDC (ICC = 0) and variability for children with CP (% exact agreement = 47%-50%). The Semmes Weinstein monofilaments, single-point localization, and both static and moving two-point discrimination are recommended for use in practice and research. Although recommended to provide a comprehensive assessment, the measures of double simultaneous, stereognosis, and tactile texture perception may not be responsive to change over time in children with unilateral CP. PMID- 22309075 TI - Use of X-ray absorption spectroscopy to speciate manganese in airborne particulate matter from five counties across the United States. AB - The purpose of this study is to characterize manganese oxidation states and speciation in airborne particulate matter (PM) and describe how these potentially important determinants of PM toxicity vary by location. Ambient PM samples were collected from five counties across the US using a high volume sequential cyclone system that collects PM in dry bulk form segregated into "coarse" and "fine" size fractions. The fine fraction was analyzed for this study. Analyses included total Mn using ICP-MS and characterization of oxidation states and speciation using X ray absorption spectroscopy (XAS). XAS spectra of all samples and ten standard compounds of Mn were obtained at the National Synchrotron Light Source. XAS data was analyzed using Linear Combination Fitting (LCF). Results of the LCF analysis describe differences in composition between samples. Mn(II) acetate and Mn(II) oxide are present in all samples, while Mn(II) carbonate and Mn(IV) oxide are absent. To the best of our knowledge, this is the first paper to characterize Mn composition of ambient PM and examine differences between urban sites in the US. Differences in oxidation state and composition indicate regional variations in sources and atmospheric chemistry that may help explain differences in health effects identified in epidemiological studies. PMID- 22309076 TI - Adding ADAM12 in risk calculation program does not improve the detection rate of trisomies 18 and 13 in first trimester screening. AB - OBJECTIVE: To investigate first trimester levels of ADAM12 in trisomy 18 and 13 pregnancies and whether incorporating ADAM12 in the LifeCycleTM risk calculation program of trisomy 18 and trisomy 13 screenings can improve the detection rates of trisomies 18 and 13. METHODS: ADAM12 was incorporated in the LifeCycleTM risk calculation program. A specific algorithm with cut-off of 1:200 for screening of trisomies 18 and 13 was employed. Detection rates for trisomies 18 and 13 were calculated. RESULTS: There was a significant difference in ADAM12 levels between trisomy 18 pregnancies and controls during the gestation weeks 9 + 0 - 10 + 6, but not thereafter. In trisomy 13 pregnancies there was no difference in weeks 9 + 0 - 10 + 6, but there was in 11 + 0 - 12 + 6. The specific algorithms for trisomies 18 and 13 combined with algorithm for trisomy 21 yielded detection rates of 73.7% and 66.7%, respectively. The combined false positive rate was 4.6%. Adding ADAM12, the detection rate for trisomy 18 was the same, at 73.7% and for trisomy 13, at 66.7%. CONCLUSION: ADAM12 did not improve the detection rate. PMID- 22309078 TI - Editorial [the emperor of all academic and cultural maladies in scientific writing: plagiarism and auto-plagiarism]. PMID- 22309079 TI - A meta-analysis and systematic review on the effect of probiotics in acute diarrhea. AB - OBJECTIVES: Diarrhea the second leading cause of death in childhood is caused by a variety of organisms. Rehydration reduces the risk of death but it is not effective in shortening duration of disease. Recently, probiotics have been recommended for prevention or treatment of gastrointestinal disorders including diarrhea. Considering existing documents from different aspects, it seems that results are somehow controversial or non-conclusive. Thus, we aimed to meta analyze clinical trials to show actual benefit of probiotics in treatment of diarrhea. METHODOLOGY: The literature search provided 1228 articles while only 19 articles focusing on the analyses performed on children were eligible to be included in the meta-analysis with a total of 3867 patients enrolled in the study. Studies in adults' diarrhea, HIV patients, diarrhea induced by Clostridium difficile, radiation and chemotherapy were also systematically reviewed. RESULTS: The meta-analysis showed that probiotics decrease the duration of diarrhea and fever significantly in children while their effects on the duration of hospitalization, vomiting and number of stools per day were not significant. The results of systematic review on adults' diarrhea, amoebiasis, clostridium difficile-associated diarrhea, diarrhea in HIV positive patients, radiation induced diarrhea, and chemotherapy-induced diarrhea did not support efficacy of probiotics in acute diarrhea. CONCLUSION: Probiotics may reduce duration of diarrhea and fever in children but their exact efficacy in treatment of diarrhea is not obvious yet. PMID- 22309080 TI - Bronchoalveolar lavage in hypersensitivity pneumonitis: a series of 139 patients. AB - Hypersensitivity pneumonitis (HP) is characterized by a lymphocytic alveolitis, classically delineated by an increase of CD8+ lymphocytes, with an inversion of the CD4+/CD8+ ratio. The aim of this study is both to describe the yield and cell bronchoalveolar lavage (BAL) profile and to revisit the assumption of low BAL CD4/CD8 ratio in the diagnosis of HP. A multicentric study was conducted on 139 patients who fulfilled the standardized diagnostic criteria of HP, mainly affected by farmer's lung. Mean total cell count in BAL fluid was 594 +/- 401.10(3) cells /ml. Prominent absolute lymphocytic alveolitis, moderate neutrophilia, and mild eosinophilia and mastocytosis were found. Mean CD4/CD8 ratio was 3.8 +/- 6.1 (median 2.1). Thirty four percent of the patients showed lymphocytic CD8 alveolitis (ratio < 1). The CD4/CD8 ratio was not different between forms, etiologies of HP, and time elapsed since last antigen exposure, but was higher in women (p=0.02). BAL in HP shows high total cell and lymphocyte counts, moderate neutrophilia, and mild eosinophilia and mastocytosis. An absence of low CD4/CD8 ratio should not at all exclude diagnosis. PMID- 22309081 TI - Revision of immunopathogenesis and laboratory interpretation for food allergy in atopic dermatitis. AB - Atopic dermatitis is an allergic inflammatory skin disease that is characterized by late eczematous skin lesions which result from non-IgE-mediated immune responses. It is well known that food allergy is an important cause of atopic dermatitis. Moreover, with recent advances in the diagnosis and treatment of food allergy, it becomes possible to elucidate the role of IgE- and non-IgE-mediated food allergies. Interprerations for blood eosinophil counts and total serum IgE levels are updated based on the immunopathogenesis of AD relating with these IgE- and non-IgE-mediated food allergies. The clinical significances of skin prick test and allergen-specific IgE are re-evaluated according to the out-to in and in to out sensitization. Atopic march is reconsturcted by the sequential sensitization of foods and aeroallergens. In this review, the revized immunopathogenesis and relevant interpretations of food allergy in atopic dermatitis are described for the evaluation of precise clinical status of AD. PMID- 22309082 TI - Modulation of MMP-9 pathway by lycopene in macrophages and fibroblasts exposed to cigarette smoke. AB - Matrix metalloproteinase-9 (MMP-9) has been implicated in both inflammation and fibrosis. It has been reported that cigarette smoke induced MMP-9 expression and that lycopene may act as an anti-inflammatory agent and may counteract several signal pathways affected by cigarette smoke exposure. However, at the moment, it is unknown if lycopene may inhibit cigarette smoke-induced MMP-9 expression. Presently, we examined the inhibitory mechanism of lycopene on MMP-9 induction in cultured human macrophages (THP-1 cells), in isolated rat alveolar macrophages (AMs) and in cultured RAT-1 fibroblasts, all cellular sources of MMP-9, exposed to cigarette smoke extract (CSE). CSE induced a marked increase in MMP-9 expression in cultured as well as in isolated cells. A 8 h-lycopene pre-treatment (0.5-2 MUM) reduced CSE-mediated MMP-9 induction in a dose- and time-dependent manner. Lycopene attenuated CSE-mediated activation of Ras, enhancing the levels of this protein in the cytosolic fraction. Moreover, lycopene inhibited CSE induced ERK1/2 and NF-kappaB activation in a dose-dependent manner. Lycopene mediated inhibition of MMP-9 was reversed by mevalonate and associated with a reduced expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Taken together, these results suggest that lycopene may inhibit CSE-mediated MMP 9 induction, primarily by blocking prenylation of Ras in a signaling pathway, in which MEK1/2-ERK1/2 and NF-kappaB are involved. PMID- 22309083 TI - Inflammatory mechanisms and oxidative stress in Peyronie's disease: therapeutic "rationale" and related emerging treatment strategies. AB - Peyronie's disease (PD) is a connective tissue disorder characterized by a fibrous plaque involving the tunica albuginea of the penis. The inelastic fibrous plaque leads to a penile curvature. Several Authors have suggested an immunological genesis of this disease, others have linked PD with Dupuytren's contracture. Signs of this disease are curvature, penile pain, penile deformity, difficulty with coitus, shortening, hinging, narrowing and erectile dysfunction. The natural history of PD and the clinical course can develop from spontaneous resolution of symptoms to progressive penile deformity and impotence. Surgical treatment is indicated when patients fail the conservative medical treatment and however, only in case of disease stabilization with a condition of impossibility of penetration. The medical treatment is indicated in the development stage of PD for at least one year after diagnosis and whenever in case of penile pain. Current non-surgical therapy includes vitamin-E, verapamil, para-aminobenzoate, propoleum, colchicine, carnitine, tamoxifen, interferons, collagenase, hyaluronidase, cortisone, pentoxifylline, superoxide dismutase, iontophoresis, radiation, extracorporeal shock wave therapy (ESWT) and the penile extender. The etiology of this fibrotic disease is not widely known, although in recent years pathophysiological knowledge has evolved and new studies propose the penile trauma as cause of the disease. The penile trauma results in a delamination of the tunica albuginea with a consequent small hematoma, then the process evolves as an inflammation with accumulation of inflammatory cells and production of reactive oxygen species (ROS). In the course of the inflammation, Peyronie's disease occurs due to the activation of nuclear factor kappa-B, that induces the production of inducible nitric oxide synthase (iNOS), with an increase of nitric oxide, leading to increased production of peroxynitrite anion. All these processes result in the proliferation of fibroblasts and myo-fibroblasts and excessive production of collagen between the layers of the tunica albuginea (penile plaque). Referring to the current knowledge of inflammatory and oxidative mechanisms of PD, a possible therapeutic strategy is then analyzed. PMID- 22309084 TI - 15-Deoxy-Delta(12,14)-prostaglandin J2 exerts pro- and anti-inflammatory effects in mesangial cells in a concentration-dependent manner. AB - Cyclopentenone prostaglandins play a modulatory role in inflammation, in part through their ability to covalently modify key proinflammatory proteins. Using mesangial cells as a cellular model of inflammation we have observed that 15 deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) exerts a biphasic effect on cell activation by cytokines, with nanomolar concentrations eliciting an amplification of nitric oxide (NO) production and iNOS and COX-2 levels, and concentrations of 5 MUM and higher inhibiting proinflammatory gene expression. An analog of 15d-PGJ(2) lacking the cyclopentenone structure (9,10-dihydro-15d PGJ(2)) showed reduced ability to elicit both types of effects, suggesting that the electrophilic nature of 15d-PGJ(2) is important for its biphasic action. Interestingly, the switch from stimulatory to inhibitory actions occurred within a narrow concentration range and correlated with the ability of 15d-PGJ(2) to induce heme oxygenase 1 and gamma-GCSm expression. These events are highly dependent on the triggering of the antioxidant response, which is considered as a sensor of thiol group modification. Indeed, the levels of the master regulator of the antioxidant response Nrf2 increased upon treatment with concentrations of 15d PGJ(2) above 5 MUM, an effect that could not be mimicked by 9,10-dihydro-15d PGJ(2). Thus, an interplay of redox and electrophilic signalling mechanisms can be envisaged by which 15d-PGJ(2), as several other redox mediators, could contribute both to the onset and to the resolution of inflammation in a context or concentration-dependent manner. PMID- 22309086 TI - Polyembryony in Melastomataceae from Brazilian Cerrado: multiple embryos in a small world. AB - Polyembryony has been commonly associated with apomixis in the angiosperms and seems to be more common than expected, even in biomes where sexual reproduction processes are predominant. Recent studies in Cerrado, the Neotropical savannas of Central Brazil, showed high frequencies of apomixis and polyembryony and indicated these processes as reproductive and evolutionary alternatives for plants in these areas. In this sense, we investigated the occurrence of polyembryony and its relationships with ecological (season and type of dispersal, ploidy, species distribution and breeding system) and taxonomic (tribe) factors in the Melastomataceae, a mostly tropical family already known for its high frequency of apomixis and very common in Cerrado. We collected seeds from 69 populations of 53 species, which were sown in germination chambers. After seed germination, the presence and number of seedlings per seed were evaluated as a method to estimate polyembryony. We encountered 18 species (33.96%) with polyembryony (more than one seedling, or gemellar seedlings, originated per seed) concentrated in species of the tribe Miconieae (64%) and Microlicieae (16.67%), but absent in Melastomeae. Monoembryony was present only in sexual species, while all apomictic species were polyembryonic. In Miconia, the polyembryony was correlated with polyploidy, and monoembryony with diploid species. Polyembryony was more common among species with wide distribution in the Cerrado region, which indicates that the presence of gemellar seedlings is important for establishment and survival of the group in the Cerrado biome. PMID- 22309085 TI - Comparison of oxidative stress and inflammation induced by different intravenous iron sucrose similar preparations in a rat model. AB - Iron sucrose originator (IS(ORIG)) has been used to treat iron deficiency and iron deficiency anemia for decades. Iron sucrose similars (ISSs) have recently entered the market. In this non-clinical study of non-anemic rats, five doses (40 mg iron/kg body weight) of six ISSs marketed in Asian countries, IS(ORIG) or saline solution (control) were administered intravenously over four weeks to compare their toxicologic effects. Vasodilatory effects, impaired renal function and hepatic damage were only observed in the ISS groups. Significantly elevated serum iron and transferrin saturation levels were observed in the ISS groups suggesting a higher release of iron resulting in higher amounts of non transferrin bound (free) iron compared to IS(ORIG). This might explain the elevated oxidative stress and increased levels of inflammatory markers and antioxidant enzymes in the liver, heart and kidneys of ISS-treated animals. Physico-chemical analyses showed that the molecular structure of most of the ISSs differed greatly from that of the IS(ORIG). These differences may be responsible for the organ damage and oxidative stress observed in the ISS groups. Significant differences were also found between different lots of a single ISS product. In contrast, polarographic analyses of three different IS(ORIG) lots were identical, indicating that the molecular structure and thus the manufacturing process for IS(ORIG) is highly consistent. Data from this study suggest that ISSs and IS(ORIG) differ significantly. Therefore, before widespread use of these products it would be prudent to evaluate additional non-clinical and/or clinical data proving the safety, therapeutic equivalence and interchangeability of ISSs with IS(ORIG). PMID- 22309087 TI - Nonword reading: comparing dual-route cascaded and connectionist dual-process models with human data. AB - Two prominent dual-route computational models of reading aloud are the dual-route cascaded (DRC) model, and the connectionist dual-process plus (CDP+) model. While sharing similarly designed lexical routes, the two models differ greatly in their respective nonlexical route architecture, such that they often differ on nonword pronunciation. Neither model has been appropriately tested for nonword reading pronunciation accuracy to date. We argue that empirical data on the nonword reading pronunciation of people is the ideal benchmark for testing. Data were gathered from 45 Australian-English-speaking psychology undergraduates reading aloud 412 nonwords. To provide contrast between the models, the nonwords were chosen specifically because DRC and CDP+ disagree on their pronunciation. Both models failed to accurately match the experiment data, and both have deficiencies in nonword reading performance. However, the CDP+ model performed significantly worse than the DRC model. CDP++, the recent successor to CDP+, had improved performance over CDP+, but was also significantly worse than DRC. In addition to highlighting performance shortcomings in each model, the variety of nonword responses given by participants points to a need for models that can account for this variety. PMID- 22309088 TI - Anticipation from biological motion: the goalkeeper problem. AB - People can often anticipate the outcome of another person's actions based on visual information available in the movements of the other person's body. We investigated this problem by studying how goalkeepers anticipate the direction of a penalty kick in soccer. The specific aim was to determine whether the information used to anticipate kick direction is best characterized as local to a particular body segment or distributed across multiple segments. In Experiment 1, we recorded the movements of soccer players as they kicked balls into a net. Using a novel method for analyzing motion capture data, we identified sources of local and distributed information that were reliable indicators of kick direction. In Experiments 2 and 3, subjects were presented with animations of kickers' movements prior to foot-to-ball contact and instructed to judge kick direction. Judgments were consistent with the use of distributed information, with a possible small contribution of local information. PMID- 22309089 TI - An investigation of the role of grapheme units in word recognition. AB - In most current models of word recognition, the word recognition process is assumed to be driven by the activation of letter units (i.e., that letters are the perceptual units in reading). An alternative possibility is that the word recognition process is driven by the activation of grapheme units, that is, that graphemes, rather than letters, are the perceptual units in reading. If so, there must be representational units for multiletter graphemes like CH and PH, which play a key role in this process. We examined this idea in four masked priming experiments. Primes were created by transposing, replacing entirely, or removing one component of either multiletter graphemes or two adjacent letters that each represented a grapheme, using both English and Spanish stimuli. In none of the experiments was there any evidence of differential priming effects depending on whether the two letters being manipulated formed a single grapheme or formed two separate graphemes. These data are most consistent with the idea that multiletter graphemes have no special status at the earliest stages of word processing and, therefore, that word recognition is, indeed, driven by the activation of units for individual letters. PMID- 22309090 TI - Proton transport pathways in [NiFe]-hydrogenase. AB - Hydrogenases reversibly catalyze the production of molecular hydrogen. Current interest in these enzymes is focused on understanding the catalysis, since this may prove useful for hydrogen-based fuel cell and photosynthetic hydrogen production cell technologies. A key step in the hydrogenase catalytic cycle and the focus of this work is proton transport (PT) to and from the active site. The PT mechanism of the enzyme is studied using reactive molecular dynamics simulations of the full protein and the excess proton transfers via the multistate empirical valence bond (MS-EVB) method. Pathways connecting the bulk and the active site are located that suggest possible participation by several protonatable residues. PT free energy surfaces are calculated to differentiate the pathways. PMID- 22309091 TI - Multi-directional in vivo tensile skin stiffness measurement for the design of a reproducible tensile strain elastography protocol. AB - BACKGROUND/AIMS: Elastography is a promising new medical imaging modality, displaying spatial distribution of biomechanical properties such as local tissue strain response to an applied stress. To develop a reproducible test protocol for skin elastography, the effect of various parameters on skin stiffness measurements was investigated. METHODS: The parameters investigated were: history of skin loading before test loading (preconditioning), direction of test loading (anisotropy) and posture (pre-stress). If a sample of skin is loaded, its stiffness will temporarily change. Finally, the reproducibility of skin stiffness and anisotropy measurements, using the developed techniques, was investigated. RESULTS: By measuring how the stiffness changed with different time delays between loading cycles, the time required for healthy skin to return to its original pre-loaded state was in the region of 125 s. A second finding, which supports and extends previous work, was that skin stiffness varied with direction, by an approximate factor of 2, and that anisotropy was less apparent with preconditioned skin than non-preconditioned skin. Study of the effect of posture showed that care needs to be taken over which stiffness measure is used. For example, measurement of the load at a given displacement was found to be highly dependent on posture, whereas measurement of the phase III stiffness was independent of posture. CONCLUSION: It was shown that when the measurement variables and methods of analysis were standardised, skin stiffness could be measured reproducibly enough to distinguish between the stiffest and softest directions, and that these methods allowed formation of skin elastograms free from confounding influences. PMID- 22309093 TI - Dissolved organic matter enhances microbial mercury methylation under sulfidic conditions. AB - Dissolved organic matter (DOM) is generally thought to lower metal bioavailability in aquatic systems due to the formation of metal-DOM complexes that reduce free metal ion concentrations. However, this model may not be pertinent for metal nanoparticles, which are now understood to be ubiquitous, sometimes dominant, metal species in the environment. The influence of DOM on Hg bioavailability to microorganisms was examined under conditions (0.5-5.0 nM Hg and 2-10 MUM sulfide) that favor the formation of beta-HgS(s) (metacinnabar) nanoparticles. We used the methylation of stable-isotope enriched (201)HgCl(2) by Desulfovibrio desulfuricans ND132 in short-term washed cell assays as a sensitive, environmentally significant proxy for Hg uptake. Suwannee River humic acid (SRHA) and Williams Lake hydrophobic acid (WLHPoA) substantially enhanced (2 to 38-fold) the bioavailability of Hg to ND132 over a wide range of Hg/DOM ratios (9.4 pmol/mg DOM to 9.4 nmol/mg DOM), including environmentally relevant ratios. Methylmercury (MeHg) production by ND132 increased linearly with either SRHA or WLHPoA concentration, but SRHA, a terrestrially derived DOM, was far more effective at enhancing Hg-methylation than WLHPoA, an aquatic DOM dominated by autochthonous sources. No DOM-dependent enhancement in Hg methylation was observed in Hg-DOM-sulfide solutions amended with sufficient l-cysteine to prevent beta-HgS(s) formation. We hypothesize that small HgS particles, stabilized against aggregation by DOM, are bioavailable to Hg-methylating bacteria. Our laboratory experiments provide a mechanism for the positive correlations between DOC and MeHg production observed in many aquatic sediments and wetland soils. PMID- 22309095 TI - Genomic and transcriptomic alterations following hybridisation and genome doubling in trigenomic allohexaploid Brassica carinata * Brassica rapa. AB - Allopolyploidisation is a prominent evolutionary force that involves two major events: interspecific hybridisation and genome doubling. Both events have important functional consequences in shaping the genomic architecture of the neo allopolyploids. The respective effects of hybridisation and genome doubling upon genomic and transcriptomic changes in Brassica allopolyploids are unresolved. In this study, amplified fragment length polymorphism (AFLP), methylation-sensitive amplification polymorphism (MSAP) and cDNA-AFLP approaches were used to track genetic, epigenetic and transcriptional changes in both allohexaploid Brassica (ArArBcBcCcCc genome) and triploid hybrids (ArBcCc genome). Results from these groups were compared with each other and also to their parents Brassica carinata (BBCC genome) and Brassica rapa (AA genome). Rapid and dramatic genetic, DNA methylation and gene expression changes were detected in the triploid hybrids. During the shift from triploidy to allohexaploidy, some of the hybridisation induced alterations underwent reversion. Additionally, novel genetic, epigenetic and transcriptional alterations were also detected. The proportions of A-genome specific DNA methylation and gene expression alterations were significantly greater than those of BC-genome-specific alterations in the triploid hybrids. However, the two parental genomes were equally affected during the ploidy shift. Hemi-CCG methylation changes induced by hybridisation were recovered after genome doubling. Full-CG methylation changes were a more general process initiated in the hybrid and continued after genome doubling. These results indicate that genome doubling could ameliorate genomic and transcriptomic alterations induced by hybridisation and instigate additional alterations in trigenomic Brassica allohexaploids. Moreover, genome doubling also modified hybridisation-induced progenitor genome-biased alterations and epigenetic alteration characteristics. PMID- 22309096 TI - Performance of rural health clinics: an examination of efficiency and Medicare beneficiary outcomes. AB - INTRODUCTION: In 2011, some 3800 Rural Health Clinics (RHCs) delivered primary care in underserved rural areas throughout the USA. To date, little research has been conducted to identify the variability in RHC performance. In an effort to address the knowledge gaps, a national, longitudinal study was conducted of a panel of 3565 RHCs. The goals of the study were to determine: (1) the relationship between two aspects of performance: efficiency and effectiveness; and (2) the factors that influence variation in RHC performance. METHODS: A non experimental study of RHC performance was conducted using 2 years of secondary data from multiple sources. A study panel of RHCs was formed. This panel was composed of all RHCs continuously in operation during the period 2006-2007. The study panel was divided into two subsets - one for the provider-based clinics; another for the independent clinics. The individual RHC was the unit of analysis throughout the study. Descriptive statistics were calculated for each subset. Bivariate analyses was conducted of the relationships between the clinic characteristics and the performance outcome measures, as well as the interrelationships between various clinic characteristics using chi2, t-tests, Cramer's V, Pearson correlation, and Spearman correlation statistics. Next, using covariance structure analysis, the interrelationships were examined among the context (community or demographic factors), design (organizational structure and other mediating factors), and performance (efficiency and effectiveness) of RHCs. Three hypotheses were tested: (1) the effectiveness of RHCs is positively influenced by efficiency; (2) there is a reciprocal relationship between RHC efficiency and effectiveness; and (3) large RHCs are more efficient than small RHCs. RESULTS: To test the hypotheses that effectiveness of RHCs is positively influenced by efficiency and that there is a reciprocal relationship between efficiency and effectiveness, two covariance structure models were developed and revised: one for independent and one for provider-based RHCs. However, the revised models were not supported by the data. To test the hypothesis that large RHCs are more efficient than small ones, two additional efficiency-based structural equation models were constructed (one for independent RHCs and another for provider-based RHCs). Both of these models were supported by the data (independent model: chi2 = 13.8, df = 8, p = 0.088, relative chi2 = 1.723, adjusted goodness of fit index [AGFI] = .981, root mean square error of approximation [RMSEA] = .034; provider-based model: chi2 = 19.011, df = 8, p = 0.015, relative chi2 = 2.376, AGFI = .978, RMSEA = .043). CONCLUSION: This study examined the relationship between efficiency and effectiveness of RHCs. In addition, it identified several factors that influence the variation in RHC performance. The study has implications for optimizing RHC performance, providing quality services to rural populations, and enhancing the value of RHC data. The present is a critical time in the history of RHCs as they transition to meet the goals and expectations of the US health system reform. Additional research is needed to quantify and trend RHCs' contribution to the rural health delivery system in order to optimize their service to rural populations. PMID- 22309100 TI - Optimizing curettage with a 'backhand'. PMID- 22309101 TI - Screening-level risk assessment of Coxiella burnetii (Q fever) transmission via aeration of drinking water. AB - A screening-level risk assessment of Q fever transmission through drinking water produced from groundwater in the vicinity of infected goat barnyards that employed aeration of the water was performed. Quantitative data from scientific literature were collected and a Quantitative Microbial Risk Assessment approach was followed. An exposure model was developed to calculate the dose to which consumers of aerated groundwater are exposed through aerosols inhalation during showering. The exposure assessment and hazard characterization were integrated in a screening-level risk characterization using a dose-response model for inhalation to determine the risk of Q fever through tap water. A nominal range sensitivity analysis was performed. The estimated risk of disease was lower than 10(-4) per person per year (pppy), hence the risk of transmission of C. burnetii through inhalation of drinking water aerosols is very low. The sensitivity analysis shows that the most uncertain parameters are the aeration process, the transport of C. burnetii in bioaerosols via the air, the aerosolization of C. burnetii in the shower, and the air filtration efficiency. The risk was compared to direct airborne exposure of persons in the vicinity of infected goat farms; the relative risk of exposure through inhalation of drinking water aerosols was 0.002%. PMID- 22309102 TI - Magnetic resonance imaging characterization of hepatocellular carcinoma expressing progenitor cell markers. PMID- 22309103 TI - Proton and calcium-gated ionic mesochannels: phosphate-bearing polymer brushes hosted in mesoporous thin films as biomimetic interfacial architectures. AB - Rational construction of interfaces based on multicomponent responsive systems in which molecular transport is mediated by structures of nanoscale dimensions has become a very fertile research area in biomimetic supramolecular chemistry. Herein, we describe the creation of hybrid mesostructured interfaces with reversible gate-like transport properties that can be controlled by chemical inputs, such as protons or calcium ions. This was accomplished by taking advantage of the surface-initiated polymerization of 2-(methacryloyloxy)ethyl phosphate (MEP) monomer units into and onto mesoporous silica thin films. In this way, phosphate-bearing polymer brushes were used as "gatekeepers" located not only on the outer surface of mesoporous thin films but also in the inner environment of the porous scaffold. Pore-confined PMEP brushes respond to the external triggering chemical signals not only by altering their physicochemical properties but also by switching the transport properties of the mesoporous film. The ion-gate response/operation was based on the protonation and/or chelation of phosphate monomer units in which the polymer brush works as an off-on switch in response to the presence of protons or Ca(2+) ions. The hybrid meso-architectured interface and their functional features were studied by a combination of experimental techniques including ellipso-porosimetry, cyclic voltammetry, X-ray reflectivity, grazing incidence small-angle X-ray scattering, X-ray photoelectron spectroscopy, and in situ atomic force microscopy. In this context, we believe that the integration of stimuli-responsive polymer brushes into nanoscopic supramolecular architectures would provide new routes toward multifunctional biomimetic nanosystems displaying transport properties similar to those encountered in biological ligand-gated ion channels. PMID- 22309105 TI - Assessing the potential of candidate DNA barcodes for identifying non-flowering seed plants. AB - In plants, matK and rbcL have been selected as core barcodes by the Consortium for the Barcode of Life (CBOL) Plant Working Group (PWG), and ITS/ITS2 and psbA trnH were suggested as supplementary loci. Yet, research on DNA barcoding of non flowering seed plants has been less extensive, and the evaluation of DNA barcodes in this division has been limited thus far. Here, we evaluated seven markers (psbA-trnH, matK, rbcL, rpoB, rpoC1, ITS and ITS2) from non-flowering seed plants. The usefulness of each region was assessed using four criteria: the success rate of PCR amplification, the differential intra- and inter-specific divergences, the DNA barcoding gap and the ability to discriminate species. Among the seven loci tested, ITS2 produced the best results in the barcoding of non flowering seed plants. In addition, we compared the abilities of the five most recommended markers (psbA-trnH, matK, rbcL, ITS and ITS2) to identify additional species using a large database of gymnosperms from GenBank. ITS2 remained effective for species identification in a wide range of non-flowering seed plants: for the 1531 samples from 608 species of 80 diverse genera, ITS2 correctly authenticated 66% of them at the species level. In conclusion, the ITS2 region can serve as a useful barcode to discriminate non-flowering seed plants, and this study will contribute valuable information for the barcoding of plant species. PMID- 22309106 TI - The roles of biofilm matrix polysaccharide Psl in mucoid Pseudomonas aeruginosa biofilms. AB - The opportunistic pathogen Pseudomonas aeruginosa causes life-threatening, persistent infections in patients with cystic fibrosis (CF). Persistence is attributed to the ability of these bacteria to form structured communities (biofilms). Biofilms rely on an extracellular polymeric substances matrix to maintain structure. Psl exopolysaccharide is a key matrix component of nonmucoid biofilms, yet the role of Psl in mucoid biofilms is unknown. In this report, using a variety of mutants in a mucoid P. aeruginosa background, we found that deletion of Psl-encoding genes dramatically decreased their biofilm formation ability, indicating that Psl is also a critical matrix component of mucoid biofilms. Our data also suggest that the overproduction of alginate leads to mucoid biofilms, which occupy more space, whereas Psl-dependent biofilms are densely packed. These data suggest that Psl polysaccharide may have significant contributions in biofilm persistence in patients with CF and may be helpful for designing therapies for P. aeruginosa CF infection. PMID- 22309107 TI - Clinical correlations of hypocomplementaemia in systemic sclerosis: an analysis of the EULAR Scleroderma Trial and Research group (EUSTAR) database. PMID- 22309108 TI - Feasibility of a porcine oral mucosa equivalent: a preclinical study. AB - Oral tissue engineering aims to treat and fill tissue deficits caused by congenital defects, facial trauma, or malignant lesion surgery, as well as to study the biology of oral mucosa. The Food and Drug Administration (FDA) and the European Medicines Agency (EMA) require a large animal model to evaluate cell based devices, including tissue-engineered oral mucosa, prior to initiating human clinical studies. Porcine oral mucosa is non-keratinized and resembles that of humans more closely than any other animal in terms of structure and composition; however, there have not been any reports on the reconstruction of a porcine oral mucosa equivalent, probably due to the difficulty to culture porcine fibroblasts. In this study, we demonstrate the feasibility of a 3D porcine oral mucosa equivalent based on a collagen-GAG-chitosan scaffold, as well as reconstructed porcine epithelium by using an amniotic membrane as support, or without any support in form of epithelial cell sheets by using thermoresponsive culture plates. Explants technique was used for the isolation of the porcine fibroblasts and a modified fibroblast medium containing 20% fetal calf serum was used for their culture. The histological and transmission electron microscopic analyses of the resulting porcine oral mucosa models showed the presence of non-keratinized epithelia expressing keratin 13, the major differentiation marker of non keratinized oral mucosa, in all models, and the presence of newly synthesized collagen fibers in the lamina propria equivalent of the full-thickness model, indicating the functionality of porcine fibroblasts. PMID- 22309109 TI - Functional reconstitution of defective myeloid dendritic cells in chronic hepatitis C infection on successful antiviral treatment. AB - OBJECTIVE: Poor cellular trafficking and suboptimal T-cell responses in liver, the hall marks of chronic hepatitis C virus (CHC) infection, might be attributed to defective antigen presentation. Controversy exists regarding role of myeloid dendritic cells (DCs) in CHC and response to antiviral treatment. This study examines functional status of DCs before and after completion of treatment with the aim to find any modulatory effect. DESIGN: Frequency and functions of monocyte-derived DCs (mo-DCs) were evaluated in CHC (n = 25), before the start of therapy (CHC(0) ). These patients were then put on treatment with peg-interferon alpha plus ribavirin for 24 or 48 weeks, and the mo-DC functions were evaluated after 6 months of completion of treatment (CHC(6) ) again, using multicolour flow cytometry, endocytosis assay, cytokine assay and mixed lymphocyte reaction. RESULTS: Pre-treatment frequency of mo-DCs in CHC(0) was lower than that in healthy controls, which became close to normal in patients who achieved virological response (SVR+, n = 20) but not in non-responders (SVR-, n = 5). Pre treatment levels of CD83, CD80 and CD86 on mo-DC in SVR(0) +, but not SVR(0) -, got upregulated after lipopolysaccharide stimulation supporting the hypothesis that DCs play deciding role in response to therapy. Post-treatment allostimulatory and phagocytosing capacity of mo-DCs in SVR+ patients indicated regain in functional capacity in these patients but not in SVR- patients. CONCLUSIONS: Our results indicate that DCs in CHC patients exhibiting mature and functional phenotype prior to therapy achieve sustained virological response suggesting that functional modulation of defective DCs is directly associated with successful response to therapy. PMID- 22309110 TI - Gold nanoparticle-aluminum oxide adsorbent for efficient removal of mercury species from natural waters. AB - We report a new adsorbent for removal of mercury species. By mixing Au nanoparticles (NPs) 13 nm in diameter with aluminum oxide (Al(2)O(3)) particles 50-200 MUm in diameter, Au NP-Al(2)O(3) adsorbents are easily prepared. Three adsorbents, Al(2)O(3), Au NPs, and Au NP-Al(2)O(3), were tested for removal of mercury species [Hg(2+), methylmercury (MeHg(+)), ethylmercury (EtHg(+)), and phenylmercury (PhHg(+))]. The Au NP adsorbent has a higher binding affinity (dissociation constant; K(d) = 0.3 nM) for Hg(2+) ions than the Al(2)O(3) adsorbent (K(d) = 52.9 nM). The Au NP-Al(2)O(3) adsorbent has a higher affinity for mercury species and other tested metal ions than the Al(2)O(3) and Au NP adsorbents. The Au NP-Al(2)O(3) adsorbent provides a synergic effect and, thus, is effective for removal of most tested metal ions and organic mercury species. After preconcentration of mercury ions by an Au NP-Al(2)O(3) adsorbent, analysis of mercury ions down to the subppq level in aqueous solution was performed by inductively coupled plasma mass spectrometry (ICP-MS). The Au NP-Al(2)O(3) adsorbent allows effective removal of mercury species spiked in lake water, groundwater, and seawater with efficiencies greater than 97%. We also used Al(2)O(3) and Au NP-Al(2)O(3) adsorbents sequentially for selectively removing Hg(2+) and MeHg(+) ions from water. The low-cost, effective, and stable Au NP Al(2)O(3) adsorbent shows great potential for economical removal of various mercury species. PMID- 22309111 TI - Ordered self-assembled locked nucleic acid (LNA) structures on gold(111) surface with enhanced single base mismatch recognition capability. AB - Locked nucleic acid (LNA) is a conformationally restricted nucleic acid analogue, which is potentially a better alternative than DNA for application in the nucleic acid based biosensor technologies, due to its efficient and sequence-specific DNA/RNA detection capability and lack of molecule-surface interaction on solid surfaces, compared to DNA. We report, for the first time, a straightforward way (based on simple immersion method) of generating an ordered self-assembled LNA monolayer, which is bioactive, onto a gold(111) surface. This layer is capable of giving rise to a stronger DNA recognition signal (4-4.5 times) than its DNA counterpart, and importantly, it can differentiate between a fully complementary DNA target and that having a single base mismatch, where the mismatch discrimination ratio is almost two times compared to the ratio relevant in case of DNA-based detection. We have presented high-resolution atomic force microscopy (AFM) topographs of the well-defined one-dimensional LNA molecular ordering (few hundred nanometers long) and of the two-dimensional ordered assembly formed over a large area (7 MUm * 7 MUm) due to parallel positioning of the one-dimensional ordered arrangements. The effects of different parameters such as LNA concentration and incubation time on LNA self-assembly have been investigated. Further, reflection absorption infrared (RAIR) spectroscopy has been applied to obtain information about the orientation of the surface-immobilized LNA molecules for the first time. It has been found that the LNA molecules undergo an orientational transition from the "lying down" to the "upright" configuration in a time scale of few hours. PMID- 22309113 TI - Diversity and distribution of sulphate-reducing bacteria in human faeces from healthy subjects and patients with inflammatory bowel disease. AB - The relative abundance of different groups of sulphate-reducing bacteria (SRB) in faecal DNA collected before and after therapy from patients suffering from Crohn's disease (CD), irritable bowel syndrome (IBS) or ulcerative colitis (UC) has been compared with that from healthy controls. Growth tests revealed that SRB were not more abundant in samples from patients with CD before treatment than in the healthy control group. For most of the 128 samples available, these preliminary results were confirmed using degenerate PCR primers that amplify the dsrAB gene. However, some samples from patients with CD before treatment contained a growth inhibitor that was absent from IBS or UC samples. In-depth sequencing of PCR-generated dsrB fragments revealed that the diversity detected was surprisingly low, with only eight strains of SRB and the sulphite-reducing bacterium, Bilophila wadsworthia, detected above the 0.1% threshold. The proportion of the two major species detected, B. wadsworthia and Desulfovibrio piger, was as high as 93.5% of the total SRB population in the healthy control group and lower in all patient groups. Four previously undescribed species were found: it is impossible to predict whether they are sulphate or sulphite-reducing bacteria. PMID- 22309114 TI - Effect modification by sex and baseline CD4+ cell count among adults receiving combination antiretroviral therapy in Botswana: results from a clinical trial. AB - The Tshepo study was the first clinical trial to evaluate outcomes of adults receiving nevirapine (NVP)-based versus efavirenz (EFV)-based combination antiretroviral therapy (cART) in Botswana. This was a 3 year study (n=650) comparing the efficacy and tolerability of various first-line cART regimens, stratified by baseline CD4(+): <200 (low) vs. 201-350 (high). Using targeted maximum likelihood estimation (TMLE), we retrospectively evaluated the causal effect of assigned NNRTI on time to virologic failure or death [intent-to-treat (ITT)] and time to minimum of virologic failure, death, or treatment modifying toxicity [time to loss of virological response (TLOVR)] by sex and baseline CD4(+). Sex did significantly modify the effect of EFV versus NVP for both the ITT and TLOVR outcomes with risk differences in the probability of survival of males versus the females of approximately 6% (p=0.015) and 12% (p=0.001), respectively. Baseline CD4(+) also modified the effect of EFV versus NVP for the TLOVR outcome, with a mean difference in survival probability of approximately 12% (p=0.023) in the high versus low CD4(+) cell count group. TMLE appears to be an efficient technique that allows for the clinically meaningful delineation and interpretation of the causal effect of NNRTI treatment and effect modification by sex and baseline CD4(+) cell count strata in this study. EFV-treated women and NVP-treated men had more favorable cART outcomes. In addition, adults initiating EFV-based cART at higher baseline CD4(+) cell count values had more favorable outcomes compared to those initiating NVP-based cART. PMID- 22309115 TI - Prodromal psychosis: diagnosis and treatment. PMID- 22309116 TI - Unusual focal intrahepatic extramedullary haematopoiesis in alpha-thalassaemia. PMID- 22309117 TI - Synthesis and characterization of amphiphilic monodisperse compounds and poly(ethylene imine)s: influence of their microstructures on the antimicrobial properties. AB - Amphiphilic monodisperse compounds (series B-I and B-II) and poly(ethylene imine)s (PEI-I, PEI-II, and PEI-III) with different microstructures were prepared from primary amines or poly(ethylene imine) with functional carbonates bearing cationic, hydrophobic, or amphiphilic groups. Their inhibition potential against proliferation of E. coli , S. aureus , and B. subtilis was investigated and their hemolytic activities were determined. The influence of the microstructures, the alkyl chain length and the distribution of cationic and hydrophobic groups, on their antimicrobial efficacy was studied. Amphiphilic compounds with long alkyl chains (C14-C18) directly linked to the cationic groups (series B-I) are more effective against both Gram-positive and Gram-negative bacteria than amphiphilic compounds in which the hydrophobic and cationic groups (series B-II) are connected by a spacer. Poly(ethylene imine)s with amphiphilic grafts (B-I) called PEI-II are more effective than amphiphilic PEIs with the same alkyl chain but with randomly linked cationic and hydrophobic graft called PEI-I or with the amphiphilic grafts (B-II) called PEI-III. The influence of the inoculum size on the MIC value was investigated exemplarily with compounds of series B-I against S. aureus . PMID- 22309118 TI - Graphene arrested in laponite-water colloidal glass. AB - Graphene production in water from graphite sources is an important technological route toward harvesting the unique properties of this material. Graphene forms thermodynamically unstable dispersions in water, limiting the use of this solvent due to aggregation. We show that graphene-water dispersions can be controlled kinetically to produce graphene by using laponite clay. Laponite exhibits rapid gelation kinetics when dispersed in water above its gelation concentration, allowing graphene aggregation to be halted after exfoliation in water at ambient conditions. The transparency of laponite colloidal glass and films is important in examining the extent of graphene exfoliation. PMID- 22309119 TI - Chorioamnionitis--the good or the evil for neonatal outcome? AB - Chorioamnionitis represents a major risk factor for preterm birth and contributes to prematurity-associated morbidity and mortality. Comparison of studies addressing neonatal outcome after exposure to either histological or clinical chorioamnionitis is hampered by the great heterogeneity regarding study cohorts and disease definitions which were applied. Moreover, the impact of exposure to inflammation in utero on neonatal outcome has become less evident with major advances in perinatal and neonatal care. Histologic chorioamnionitis evidently is associated with a reduction of incidence and severity of respiratory distress syndrome. Short-term maturational effects on the lungs of ventilated extremely premature infants are, however, accompanied by a greater susceptibility of the lung, eventually contributing to an increased risk of bronchopulmonary dysplasia. Chorioamnionitis has been shown associated with increased rate of early-onset sepsis but, according to recent data, histological chorioamnionitis might be protective against late-onset sepsis. Inconsistent data exist concerning the true role of chorioamnionitis in the development of brain lesions such as cystic periventricular leukomalacia, diffuse white matter disease, and intraventricular hemorrhage. However, an association with the development of cerebral palsy has been reported. PMID- 22309120 TI - Phytoplankton chytridiomycosis: community structure and infectivity of fungal parasites in aquatic ecosystems. AB - Fungal parasitism is recurrent in plankton communities, especially in the form of parasitic chytrids. However, few attempts have been made to study the community structure and activity of parasites at the natural community level. To analyse the dynamics of zoosporic fungal parasites (i.e. chytrids) of phytoplankton, samples were collected from February to December 2007 in two freshwater lakes. Infective chytrids were omnipresent in lakes, with higher diversity of parasites and infected phytoplankton than in previous studies. The abundance and biomass of parasites were significantly higher in the productive Lake Aydat than in the oligomesotrophic Lake Pavin, while the infection prevalence in both lakes were similar and averaged about 20%. The host species composition and their size appeared as critical for chytrid infectivity, the larger hosts being more vulnerable, including pennate diatoms and desmids in both lakes. The highest prevalence (98%) was noted for the autumn bloom of the cyanobacterium Anabaena flosaquae facing the parasite Rhizosiphon crassum in Lake Aydat. Because parasites killed their hosts, this implies that cyanobacterial blooms, and other large size inedible phytoplankton blooms as well, may not totally represent trophic bottlenecks because their zoosporic parasites can release dissolved substrates for microbial processes through host destruction, and provide energetic particles as zoospores for grazers. Overall, we conclude that the parasitism by zoosporic fungi represents an important ecological driving force in the food web dynamics of aquatic ecosystems, and infer general empirical models on chytrid seasonality and trophodynamics in lakes. PMID- 22309121 TI - Obsessive beliefs predict cognitive behavior therapy outcome for obsessive compulsive disorder. AB - Cognitive accounts of obsessive compulsive disorder (OCD) assert that core beliefs are crucial to the development, maintenance, and treatment of the disorder. There are a number of obsessive beliefs that are considered fundamental to OCD, including personal responsibility, threat estimation, perfectionism, need for certainty, importance of thoughts, and thought control. The present study investigated if pretreatment severity of obsessive beliefs, as well as the change in obsessive beliefs following treatment, predicted intensive, residential cognitive behavioral therapy (CBT) treatment outcome. A series of hierarchical regression analyses were carried out to investigate the relations between obsessive beliefs and treatment outcome. Results indicated that inflated pretreatment responsibility/threat estimation beliefs were significantly related to less overall obsessive compulsive (OC) symptom reduction at discharge, explaining 2% of the overall variance. Changes in obsessive beliefs broadly, and importance/control of thoughts specifically, were positively related to overall OC symptom reduction at discharge, respectively explaining 18% and 3.6% variance. Results are modestly consistent with a number of theoretical models, which argue that inflated responsibility, threat estimation, and thought control are important to the maintenance and treatment of OCD. PMID- 22309122 TI - Polysaccharides serve as scaffold of biofilms formed by mucoid Pseudomonas aeruginosa. AB - Chronic lung infection by mucoid Pseudomonas aeruginosa is one of the major pathologic features in patients with cystic fibrosis. Mucoid P. aeruginosa is notorious for its biofilm forming capability and resistance to immune attacks. In this study, the roles of extracellular polymeric substances from biofilms formed by mucoid P. aeruginosa were investigated. Alginate is not an essential structure component for mucoid P. aeruginosa biofilms. Genetic studies revealed that Pel and Psl polysaccharides serve as essential scaffold and mediate macrocolony formation in mucoid P. aeruginosa biofilms. The Psl polysaccharide is more important than Pel polysaccharide in mucoid P. aeruginosa biofilm structure maintenance and phagocytosis resistance. The polysaccharides were further found to protect mucoid P. aeruginosa strain from host immune clearance in a mouse model of acute lung infection. PMID- 22309123 TI - Stress distribution pattern in a root of maxillary central incisor having various root morphologies: a finite element study. AB - OBJECTIVE: To investigate stress distribution in the roots of maxillary central incisors bearing various types of root morphologies with regard to application of different types of orthodontic forces using the finite element model (FEM). MATERIALS AND METHODS: FEMs of maxillary central incisors with different root morphologies (normal, short, blunt, dilacerated, and pipette) were constructed, and orthodontic forces in various directions (intrusion, extrusion, tipping, and rotational) were applied to the tooth axis at the bracket level. RESULT: On application of various forces, significantly increased stress was seen at the apex of the root with dilacerated morphology and at the cervical one-third region of the tooth with the short root. Increased stress was observed at the middle one third region in the tooth with the pipette-shaped root during intrusion and extrusion. CONCLUSIONS: In the present study, the stress distribution pattern indicates that the maxillary central incisors with deviated root morphology are at higher risk of root resorption. PMID- 22309124 TI - The effects of varying alcohol concentrations commonly found in mouth rinses on the force decay of elastomeric chain. AB - OBJECTIVE: To test the effect of alcohol on force decay of elastomeric chains in vitro in order to determine if increasing alcohol concentrations results in an increased amount of elastomeric chain force decay. MATERIALS AND METHODS: A prospective laboratory study was completed to test the effect of alcohol exposure on orthodontic elastomeric chain. A total of 450 specimens were divided into five test groups. Two test groups were each exposed to different alcohol concentrations (14% and 26.9%) and the other two test groups were exposed to different commercially available mouth rinses (Cepacol -14% alcohol and Listerine - 26.9% alcohol) for 60 seconds twice a day. The control group followed all of the same procedures but was only exposed to deionized (DI) water. Force measurements were taken at six time points (initial, 1 day, 7 days, 14 days, 21 days, and 28 days). RESULTS: There were no significant differences among groups at the initial time point (P = .52). Statistically significant effects of time on force decay were seen in all groups. All test groups showed significantly more force decay than the control group. Only a few statistically significant differences were observed when comparing force decay among the test groups. CONCLUSIONS: Alcohol causes an increase in force decay of elastomeric chain over time. A concentration dependence of alcohol on force decay of elastomeric chain was not observed. PMID- 22309125 TI - Potential association of Helicobacter cinaedi with atrial arrhythmias and atherosclerosis. AB - Helicobacter cinaedi has been increasingly recognized as an emerging pathogen. Reports of recurrent bacteremia and isolation of H. cinaedi organisms from a patient with myopericarditis led us to postulate that H. cinaedi is associated with chronic inflammatory cardiovascular diseases such as atrial arrhythmias and atherosclerosis. To assess any association of H. cinaedi with atrial arrhythmias, a retrospective case-control study of patients attending Kumamoto University Hospital from 2005 to 2009 was performed. The arrhythmia status of these patients was determined from their electrocardiography and electrophysiological studies. Multiple logistic regression analysis was used to identify independent risk factors. In a comparison of case patients (n= 132) with control subjects (n= 137), H. cinaedi seropositivity was identified as an independent risk factor for atrial arrhythmia (odds ratio, 5.13; 95% confidence interval, 3.0-8.7; P < 0.001). There were no significant differences, however, between these two groups with respect to anti-H. pylori IgG concentrations, anti-Chlamydophila pneumoniae IgG concentrations, and other studied variables. IgG concentrations against H. cinaedi and H. pylori were inversely correlated, which suggests cross-immunity between these two bacteria. Also, to explore any association of H. cinaedi with atherosclerosis, immunohistochemical analysis of atherosclerotic aortic tissues collected post mortem from nine patients was performed. Immunohistochemistry of atherosclerotic aortic tissues from all nine patients detected H. cinaedi antigens inside CD68(+) macrophages. These findings provide the first evidence, to our knowledge, of a possible association of H. cinaedi with atrial arrhythmias and atherosclerosis. PMID- 22309126 TI - Lipase-catalyzed production of pinolenic acid concentrate from pine nut oil using a recirculating packed bed reactor. AB - Pinolenic acid (PLA) concentrate in fatty acid ethyl ester (FAEE) was efficiently produced from pine nut oil via lipase-catalyzed ethanolysis using a recirculating packed bed reactor (RPBR). The effects of reaction temperature, molar ratio, and residence time on the concentration of PLA were explored. Novozym 435 lipase from Candida antarctica showed less selectivity toward PLA esterified at the sn-3 position when temperature was increased from 45 to 55 degrees C. For the trials of molar ratio between 1: 50 and 1: 100 (pine nut oil to ethanol), there were no significant differences in the yield of PLA. Residence time of substrate in a RPBR affected significantly the PLA content as well as the yield of PLA. Optimal temperature, molar ratio (pine nut oil to ethanol), and residence time for production of PLA concentrate via lipase-catalyzed ethanolysis in a RPBR were 45 degrees C, 1: 50, and 3 min, respectively. Under these conditions, the maximal PLA content (36.1 mol%) in the concentrate was obtained during the initial 10 min of reaction. PMID- 22309127 TI - Signs of the presence of Th17 cells in chronic periodontal disease. AB - BACKGROUND AND OBJECTIVE: The aim of this study was to identify the specific markers of T helper 17 (Th17) cells and their variations in people suffering from chronic periodontal disease in comparison with normal control subjects. MATERIAL AND METHODS: In 30 patients with periodontitis and 30 normal control subjects, the mRNA expressions of interleukin (IL)-17A and retinoic orphan receptor C2 (RORC2) were measured by quantitative RT-PCR. The protein levels of IL-17A and RORC2 were also evaluated by immunohistochemistry. The levels of these markers were compared between healthy and diseased periodontal tissues by the Mann Whitney U-test. RESULTS: In periodontal lesions, IL-17A and RORC2 were significantly overexpressed compared with normal tissues. According to our immunohistochemical analysis, the number of IL-17A-positive cells and RORC2 positive cells was significantly greater in periodontal lesions compared with control sites. Moreover, there was a positive correlation between the presence of IL-17A and RORC2 transcript and protein content levels in the gingiva of diseased patients. CONCLUSION: The results demonstrated a significant increase in the number of some specific markers of Th17 cells in patients suffering from periodontal disease in comparison with normal control subjects. PMID- 22309128 TI - Healthcare costs associated with osteoarthritis in US patients. AB - BACKGROUND: Osteoarthritis is a chronic debilitating condition affecting many adults in the United States. This study was to compare pharmacologic treatments and costs for newly diagnosed and existing osteoarthritis patients to assess unmet medication treatment needs and economic burden. METHODS: This retrospective analysis of de-identified medical and pharmacy insurance claims from the MarketScan((r)) databases identified adult patients with an osteoarthritis claim in 2007. The date of the first osteoarthritis claim in 2007 served as the index. Patients were stratified into newly diagnosed and existing cohorts, based on the presence of osteoarthritis claim(s) over the 12-month pre-index period. Utilization of pain-related medications and healthcare costs was assessed in the 12-month postindex period. Multivariate analysis was conducted to adjust costs controlling for cross-cohort differences. RESULTS: Newly diagnosed osteoarthritis patients (n = 134,584) were younger (66.0 vs. 68.0, P < 0.001), had a higher proportion of men (37.4% vs. 33.9%, P < 0.001) but lower rates of comorbidities than existing patients (n = 123,653). Significantly higher proportions of newly diagnosed patients had an inpatient admission and outpatient office visit. Higher proportions of existing patients utilized a majority of the medication classes examined. Total adjusted osteoarthritis-related costs for newly diagnosed patients were $6,811 annually (95% confidence interval [CI] $6,743 to $6,887), compared to $6,407 (95% CI $6,327 to $6,477) for existing patients. Costs of pain related prescription drugs associated with osteoarthritis were $965 (95% CI $955 to $975) among new patients, less than the $1,117 (95% CI $1,107 to $1,129) among existing patients. CONCLUSION: Newly diagnosed osteoarthritis patients incurred higher annual costs, but lower pain-related prescription drug costs in the year following diagnosis than patients with existing osteoarthritis. PMID- 22309129 TI - Facile immobilization of biomolecules onto various surfaces using epoxide containing antibiofouling polymers. AB - The surface modifications of plastic or glass substrate and the subsequent immobilization of biomolecules onto the surfaces has been a central feature of the fabrication of biochips. To this end, we designed and synthesized new epoxide containing random copolymers that form stable polymer adlayers on plastic or glass surface and subsequently react with amine or sulfhydryl functional groups of biomolecules under aqueous conditions. Epoxide-containing random copolymers were synthesized by radical polymerization of three functional monomers: a monomer acting as an anchor to the surfaces, a PEG group for preventing nonspecific protein adsorption, and an epoxide group for conjugating to biomolecules. Polymer coating layers were facilely formed on cyclic olefin copolymer (COC) or glass substrate by simply dipping each substrate into a solution of each copolymer. The polymer-coated surfaces characterized by a contact angle analyzer and X-ray photoelectron spectroscopy (XPS) showed very low levels of nonspecific immunoglobulin G (IgG) adsorption compared to the uncoated bare surface (control). Using a microcontact printing (MUCP) method, antibodies as representative biomolecules could be selectively attached onto the copolymers coated glass or COC surface with high signal-to-noise ratios. PMID- 22309130 TI - Trigonal bipyramidal Dy5 cluster exhibiting slow magnetic relaxation. AB - A pentanuclear dysprosium cluster, [Dy(5)(MU(3) OH)(6)(Acc)(6)(H(2)O)(10)].Cl(9).24H(2)O (1), has been synthesized through the reaction of 1-amino-cyclohexanel-carboxylic acid (Acc) and DyCl(3).5H(2)O. Crystal structural analysis reveals that the metal core of cluster 1 shows an unprecedented trigonal bipyramidal (TBP) geometry. Magnetic studies indicate that the Dy(5) cluster exhibits slow magnetic relaxation. PMID- 22309131 TI - Artifacts in liquid-phase separations-system, solvent, and impurity peaks. PMID- 22309132 TI - Kinked p-n junction nanowire probes for high spatial resolution sensing and intracellular recording. AB - Semiconductor nanowires and other semiconducting nanoscale materials configured as field-effect transistors have been studied extensively as biological/chemical (bio/chem) sensors. These nanomaterials have demonstrated high-sensitivity from one- and two-dimensional sensors, although the realization of the ultimate pointlike detector has not been achieved. In this regard, nanoscale p-n diodes are attractive since the device element is naturally localized near the junction, and while nanowire p-n diodes have been widely studied as photovoltaic devices, their applications as bio/chem sensors have not been explored. Here we demonstrate that p-n diode devices can serve as a new and powerful family of highly localized biosensor probes. Designed nanoscale axial p-n junctions were synthetically introduced at the joints of kinked silicon nanowires. Scanning electron microscopy images showed that the kinked nanowire structures were achieved, and electrical transport measurements exhibited rectifying behavior with well-defined turn-on in forward bias as expected for a p-n diode. In addition, scanning gate microscopy demonstrated that the most sensitive region of these nanowires was localized near the kinked region at the p-n junction. High spatial resolution sensing using these p-n diode probes was carried out in aqueous solution using fluorescent charged polystyrene nanobeads. Multiplexed electrical measurements show well-defined single-nanoparticle detection, and experiments with simultaneous confocal imaging correlate directly the motion of the nanobeads with the electrical signals recorded from the p-n devices. In addition, kinked p-n junction nanowires configured as three-dimensional probes demonstrate the capability of intracellular recording of action potentials from electrogenic cells. These p-n junction kinked nanowire devices, which represent a new way of constructing nanoscale probes with highly localized sensing regions, provide substantial opportunity in areas ranging from bio/chem sensing and nanoscale photon detection to three-dimensional recording from within living cells and tissue. PMID- 22309133 TI - Is postpartum pyelonephritis associated with the same maternal morbidity as antepartum pyelonephritis? AB - OBJECTIVE: Pregnant women with pyelonephritis are at higher risk for significant morbidty than nonpregnant women with pyelonephritis. The risk from pregnancy may continue into the postpartum period. Many of the physiologic and hormonal changes that occur during pregnancy persist after delivery. The objective of this study was to compare maternal morbidity in postpartum and antepartum pyelonephritis. METHODS: A retrospective cohort analysis included all pregnant and postpartum women hospitalized for pyelonephritis at a single tertiary care hospital between January 2004 and June 2007. The postpartum period was defined as up to 6 weeks from delivery. The primary outcome measure was maternal morbidity measured by length of hospitalization. RESULTS: 256 cases of antepartum pyelonephritis and 23 cases of postpartum pyelonephritis were included in the analysis. Women in both groups were admitted for a mean of 4 days (p = 0.3). Women who were diagnosed in the postpartum period were more likely to be febrile (91.3% vs. 51.7%, p = 0.0001) and had a higher temperature on presentation (102.9 degrees F vs. 99.1 degrees F p < 0.0001). DISCUSSION: Pyelonephritis was equally morbid in the postpartum and antepartum periods. Postpartum pyelonephritis may warrant the same close inpatient observation as antepartum pyelonephritis. PMID- 22309134 TI - Aggregatibacter actinomycetemcomitans leukotoxin cytotoxicity occurs through bilayer destabilization. AB - The Gram-negative bacterium, Aggregatibacter actinomycetemcomitans, is a common inhabitant of the human upper aerodigestive tract. The organism produces an RTX (Repeats in ToXin) toxin (LtxA) that kills human white blood cells. LtxA is believed to be a membrane-damaging toxin, but details of the cell surface interaction for this and several other RTX toxins have yet to be elucidated. Initial morphological studies suggested that LtxA was bending the target cell membrane. Because the ability of a membrane to bend is a function of its lipid composition, we assessed the proficiency of LtxA to release of a fluorescent dye from a panel of liposomes composed of various lipids. Liposomes composed of lipids that form nonlamellar phases were susceptible to LtxA-induced damage while liposomes composed of lipids that do not form non-bilayer structures were not. Differential scanning calorimetry demonstrated that the toxin decreased the temperature at which the lipid transitions from a bilayer to a nonlamellar phase, while (31) P nuclear magnetic resonance studies showed that the LtxA-induced transition from a bilayer to an inverted hexagonal phase occurs through the formation of an isotropic intermediate phase. These results indicate that LtxA cytotoxicity occurs through a process of membrane destabilization. PMID- 22309136 TI - Symmetrical negative differential resistance behavior of a resistive switching device. AB - With a thin insulator sandwiched between two electrodes, the negative differential resistance (NDR) behavior has been frequently reported for its potential device applications. Here we report the experimental observation of a symmetric NDR characteristic in a resistive switching device based on TiO(2). We propose a charge storage mechanism for the NDR effect, with oxygen molecular ions working as the active source, in a thin insulating layer. Current-voltage measurements demonstrated a highly reproducible state at about 0.65 eV, and the photoelectron spectroscopy measurements showed that it complies well with the Ti3d band gap state. Our first-principle calculations confirm that charge storage and release arise from trapping and detrapping of oxygen molecular ions at the defect sites. The results and mechanism demonstrated here in a thin layer could be extended to other systems approaching molecular dimensions for device applications. PMID- 22309137 TI - Automated 3D MRI volumetry reveals regional atrophy differences in Rasmussen encephalitis. AB - PURPOSE: Rasmussen encephalitis is a chronic immune-mediated disease leading to unilateral atrophy on magnetic resonance imaging (MRI) and progressive neurologic deficits. Until now, quantitative parameters describing the course of the disease on MRI require manual intervention and are, therefore, time-consuming and observer-dependent. Furthermore, regional atrophy differences cannot be evaluated with the previously published methods. In this study we present a fully automated volumetric approach applied to serial MRI scans of 12 patients with Rasmussen encephalitis. METHODS: We retrospectively analyzed 12 patients with Rasmussen encephalitis with a disease onset between 2001 and 2008. All patients underwent a total of 66 serial MRI scans including a three-dimensional T(1) data set. The volumetric analysis was based on standard procedures of the freely available software FMRIB Software Library (FSL) and required about 45 min per scan. Furthermore, planimetric analyses were performed on 51 scans as described previously. KEY FINDINGS: The relative and absolute volume loss of the affected hemisphere was significantly higher compared to the unaffected hemisphere. Referring to regional atrophy differences our results show that the frontal lobe and the insula were preferentially involved in the atrophic process. The degree of hemispheric, parietal, and occipital atrophy was negatively correlated with the age at disease onset, indicating a more aggressive and outspread disease in young children compared to adolescents. Volumetric hemispheric ratio and planimetric hemispheric ratio correlated significantly, but planimetric hemispheric ratio underestimated the real degree of hemiatrophy, especially in patients with predominant affections outside the frontoinsular region. SIGNIFICANCE: The volumetric analysis presented here offers a precise assessment of the disease progression in Rasmussen encephalitis in an observer-independent and time-efficient manner and gives an interesting insight into the course of the disease on MRI. The degree of atrophy evaluated with this method correlates with clinical parameters and is comparable to atrophy rates in patients receiving immunotherapy in preceding planimetric MRI studies. PMID- 22309135 TI - Virulence strategies of the dominant USA300 lineage of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). AB - Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to worldwide health. Historically, MRSA clones have strictly been associated with hospital settings, and most hospital-associated MRSA (HA-MRSA) disease resulted from a limited number of virulent clones. Recently, MRSA has spread into the community causing disease in otherwise healthy people with no discernible contact with healthcare environments. These community-associated MRSA clones (CA-MRSA) are phylogenetically distinct from traditional HA-MRSA clones, and CA-MRSA strains seem to exhibit hypervirulence and more efficient host : host transmission. Consequently, CA-MRSA clones belonging to the USA300 lineage have become dominant sources of MRSA infections in North America. The rise of this successful USA300 lineage represents an important step in the evolution of emerging pathogens and a great deal of effort has been exerted to understand how these clones evolved. Here, we review much of the recent literature aimed at illuminating the source of USA300 success and broadly categorize these findings into three main categories: newly acquired virulence genes, altered expression of common virulence determinants and alterations in protein sequence that increase fitness. We argue that none of these evolutionary events alone account for the success of USA300, but rather their combination may be responsible for the rise and spread of CA-MRSA. PMID- 22309138 TI - Sequence-specific mapping of the interaction between urea and unfolded ubiquitin from ensemble analysis of NMR and small angle scattering data. AB - The molecular details of how urea interacts with, and eventually denatures proteins, remain largely unknown. In this study we have used extensive experimental NMR data, in combination with statistical coil ensemble modeling and small-angle scattering, to analyze the conformational behavior of the protein ubiquitin in the presence of urea. In order to develop an atomic resolution understanding of the denatured state, conformational ensembles of full-atom descriptions of unfolded proteins, including side chain conformations derived from rotamer libraries, are combined with random sampling of explicit urea molecules in interaction with the protein. Using this description of the conformational equilibrium, we demonstrate that the direct-binding model of urea to the protein backbone is compatible with available experimental data. We find that, in the presence of 8 M urea, between 30 and 40% of the backbone peptide groups bind a urea molecule, independently reproducing results from a model-free analysis of small-angle neutron and X-ray scattering data. Crucially, this analysis also provides sequence specific details of the interaction between urea and the protein backbone. The pattern of urea-binding along the amino-acid sequence reveals a higher level of binding in the central part of the protein, a trend which resembles independent results derived from chemical shift mapping of the urea-protein interaction. Together these results substantiate the direct binding model and provide a framework for studying the physical basis of interactions between proteins and solvent molecules. PMID- 22309140 TI - Managing the first period at home with a newborn: a grounded theory study of mothers' experiences. AB - AIM: The article aims to present a theoretical account of mothers' first period at home with their newborn in Norway. BACKGROUND: Mothers' well-being affects their babies and is therefore an important priority for public health. Early discharge after childbirth is common in many countries. In Norway, this has been practised for 5-10 years but without any distinct agreement between maternity hospitals and the community health services and without documented follow-up care. Knowledge is lacking in how mothers deal with the first period at home with the baby. METHOD: Seven focus group discussions were conducted with 26 mothers who had babies 1.5-3 months old. The grounded theory method was used to gather and analyse data. RESULTS: The mothers were strongly concerned about preserving their control and integrity in the new situation. This main concern was resolved by the strategy of prioritizing newborn care. The strategy encompassed a process of developing competence as a mother, changing focus in relationships, stretching to the critical level and seeking recognition. These parallel processes were inter-related, sometimes mutually supportive and sometimes conflicting. When conflicts occurred, prioritizing newborn care guided mothers in finding solutions. Breaches of the implied conditions in health care tended to increase mothers' level of strain and uncertainty and to influence their efficacy in breastfeeding the baby. CONCLUSION: Being a mother to a newborn is a dynamic and extensive process. Succeeding in breastfeeding seems especially sensitive and essential in motherhood. The idea that giving birth is a simple and normal situation may obscure the importance of seamless health care and the need for professional support and information. PMID- 22309139 TI - Ethanol tolerance and withdrawal severity in high drinking in the dark selectively bred mice. AB - BACKGROUND: Mouse lines are being selectively bred in replicate for high blood ethanol concentrations (BECs) achieved after limited access of ethanol (EtOH) drinking early in the circadian dark phase. High Drinking in the Dark-1 (HDID-1) mice are in selected generation S21, and the replicate HDID-2 line in generation S14. Tolerance and withdrawal symptoms are 2 of the 7 diagnostic criteria for alcohol dependence. Withdrawal severity has been found in mouse studies to be negatively genetically correlated with EtOH preference drinking. METHODS: To determine other traits genetically correlated with high DID, we compared naive animals from both lines with the unselected, segregating progenitor stock, HS/Npt. Differences between HDID-1 and HS would imply commonality of genetic influences on DID and these traits. RESULTS: Female HDID-1 and HDID-2 mice tended to develop less tolerance than HS to EtOH hypothermia after their third daily injection. A trend toward greater tolerance was seen in the HDID males. HDID-1, HDID-2, and control HS lines did not differ in the severity of acute or chronic withdrawal from EtOH as indexed by the handling-induced convulsion (HIC). Both HDID-1 and HDID-2 mice tended to have greater HIC scores than HS regardless of drug treatment. CONCLUSIONS: These results show that tolerance to EtOH's hypothermic effects may share some common genetic control with reaching high BECs after DID, a finding consistent with other data regarding genetic contributions to EtOH responses. Withdrawal severity was not negatively genetically correlated with DID, unlike its correlation with preference drinking, underscoring the genetic differences between preference drinking and DID. HDID lines showed greater basal HIC scores than HS, suggestive of greater central nervous system excitability. PMID- 22309141 TI - Comparison of FEV(3), FEV(6), FEV(1)/FEV(3) and FEV(1)/FEV(6) with usual spirometric indices. AB - BACKGROUND AND OBJECTIVE: Pulmonary function tests play an important role in the management of pulmonary diseases. One of the tests that are widely used is spirometry. Performing an acceptable spirometry manoeuvre according to the standards set by the American Thoracic Society/European Respiratory Society is difficult. The aim of this study was to compare forced expiratory volume in 3 s (FEV(3)) and forced expiratory volume in 6 s (FEV(6)) with forced vital capacity (FVC), and forced expiratory volume in 1 s FEV(1)/FEV(3) and FEV(1)/FEV(6) with FEV(1)/FVC, in order to substitute the usual spirometric manoeuvres with manoeuvres that are easier to perform. METHODS: In a cross-sectional study, spirometry was performed for 588 subjects who were referred for occupational health evaluations. The accuracy of FEV(3), FEV(6), FEV(1)/FEV(3) and FEV(1)/FEV(6) was compared with that of FVC and FEV(1)/FVC. Chi-square tests and kappa tests were used to analyse the data. RESULTS: Individuals with normal (n = 297) and abnormal spirometry (n = 291) were evaluated. The sensitivity, specificity, positive predictive value and negative predictive value of FEV(1) /FEV(6) , as compared with that of FEV(1)/FVC for detecting obstruction, were 93.56, 99.32, 98.95 and 96.09, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of FEV(6), as compared with that of FVC for detecting restriction, were 96.68, 98.65, 96.68 and 98.65, respectively. CONCLUSIONS: FEV(6) and FEV(1)/FEV(6) can be used as surrogates for FVC and FEV(1)/FVC, respectively, and these parameters showed acceptable sensitivity, specificity, positive predictive value and negative predictive value for occupational health evaluations. PMID- 22309142 TI - Evaluation of n-butyl cyanoacrylate adhesive in rat subcutaneous tissue. AB - BACKGROUND: Tissue adhesives have been widely used for wound closure, especially in children, because they are painless, fast, and easy to use and result in minimal scarring. OBJECTIVE: To analyze the biocompatibility of an adhesive based on n-butyl-cyanoacrylate in the subcutaneous tissue of rats. MATERIALS AND METHODS: Two surgical sites were prepared (approximately 3 cm apart): one on the left side of the animal and the other on the right side); polyethylene tubes were implanted in each surgical site. The tube on the left was filled with n-butyl cyanoacrylate (treated group) and the tube on the right side was unfilled (control group). After 7, 30, and 120 days, the animals were killed, and the specimens were processed for histologic analysis. RESULTS: No significant inflammatory reaction occurred in the treated group, showing results similar to the control group. CONCLUSION: This adhesive based on n-butyl-cyanoacrylate is biocompatible in the subcutaneous tissue of rats. PMID- 22309143 TI - Separation, identification, and quantitation of phenolic acids in Chinese waxberry (Myrica Rubra) juice by HPLC-PDA-ESI-MS. AB - A high-performance liquid chromatography coupled with photodiode-array spectrophotometry and electrospray ionization-mass spectrometry (HPLC-PDA-ESI-MS) method for separation and determination of phenolic acids in ethyl acetate extracts from Chinese waxberry (Myrica Rubra) juice was developed. Total of 4 phenolic acids (ferulic, caffeic, sinapic, and salicylic acids) were identified by comparing their HPLC retention times, UV-Vis absorption spectra, and simultaneously recorded mass spectra with authentic standards. Quantitation was carried out by the peak area method. The calibration curves are linear over the concentration range studied with the correlation coefficients, R(2), greater than 0.99. The contents of ferulic, caffeic, sinapic, and salicylic acids in waxberry juice samples studied were 2.76, 3.58, 2.89, and 1.92 mg/L, respectively, and they occur mainly in bound forms. All relative standard deviations were less than 4%. The recoveries range from 83.6% to 95.8% for the 4 analytes. To the authors' best knowledge, this is the first report for the identification of the sinapic and salicylic acids in Chinese waxberry products. PMID- 22309144 TI - Echocardiographic guidance for neonatal right ventricular outflow tract stent implantation. AB - The use of combined fluoroscopic and echocardiographic imaging in congenital intervention is a well-established and developing concept. We report the case of a 1.2 kg, hemodynamically unstable neonate with tetralogy of Fallot, in whom we implanted a right ventricular outflow tract stent under primarily echocardiographic guidance. This represents the smallest reported patient in whom a right ventricular outflow tract stent has been placed and the latest application of integrated echocardiography and fluoroscopy in the catheterization laboratory. PMID- 22309145 TI - Early platelet activation, inflammation and acute brain injury after a subarachnoid hemorrhage: a pilot study. PMID- 22309146 TI - A meshless microscale bone tissue trabecular remodelling analysis considering a new anisotropic bone tissue material law. AB - In this work, a novel anisotropic material law for the mechanical behaviour of the bone tissue is proposed. This new law, based on experimental data, permits to correlate the bone apparent density with the obtained level of stress. Combined with the proposed material law, a biomechanical model for predicting bone density distribution was developed, based on the assumption that the bone structure is a gradually self-optimising anisotropic biological material that maximises its own structural stiffness. The strain and the stress field required in the iterative remodelling process are obtained by means of an accurate meshless method, the Natural Neighbour Radial Point Interpolation Method (NNRPIM). Comparing with other numerical approaches, the inclusion of the NNRPIM presents numerous advantages such as the high accuracy and the smoother stress and strain field distribution. The natural neighbour concept permits to impose organically the nodal connectivity and facilitates the analysis of convex boundaries and extremely irregular meshes. The viability and efficiency of the model were tested on several trabecular benchmark patch examples. The results show that the pattern of the local bone apparent density distribution and the anisotropic bone behaviour predicted by the model for the microscale analysis are in good agreement with the expected structural architecture and bone apparent density distribution. PMID- 22309147 TI - Calcium/calmodulin inhibition of the Arabidopsis BRASSINOSTEROID-INSENSITIVE 1 receptor kinase provides a possible link between calcium and brassinosteroid signalling. AB - The receptor kinase BRI1 (BRASSINOSTEROID-INSENSITIVE 1) is a key component in BR (brassinosteroid) perception and signal transduction, and has a broad impact on plant growth and development. In the present study, we demonstrate that Arabidopsis CaM (calmodulin) binds to the recombinant cytoplasmic domain of BRI1 in a Ca2+-dependent manner in vitro. In silico analysis predicted binding to Helix E of the BRI1 kinase subdomain VIa and a synthetic peptide based on this sequence interacted with Ca2+/CaM. Co-expression of CaM with the cytoplasmic domain of BRI1 in Escherichia coli strongly reduced autophosphorylation of BRI1, in particular on tyrosine residues, and also reduced the BRI1-mediated transphosphorylation of E. coli proteins on tyrosine, threonine and presumably serine residues. Several isoforms of CaM and CMLs (CaM-like proteins) were more effective (AtCaM6, AtCaM7 and AtCML8, where At is Arabidopsis thaliana) than others (AtCaM2, AtCaM4 and AtCML11) when co-expressed with BRI1 in E. coli. These results establish a novel assay for recombinant BRI1 transphosphorylation activity and collectively uncover a possible new link between Ca2+ and BR signalling. PMID- 22309148 TI - A tribute to Joseph G. Cannon, 1926-2011. PMID- 22309149 TI - Anomalous pull-off forces between surfactant-free emulsion drops in different aqueous electrolytes. AB - A systematic study of collisions between surfactant-free organic drops in aqueous electrolyte solutions reveals the threshold at which continuum models provide a complete description of thin-film interactions. For collision velocities above ~1 MUm/s, continuum models of hydrodynamics and surface forces provide a complete description of the interaction, despite the absence of surfactant. This includes accurate prediction of coalescence at high salt concentration (500 mM). In electrolyte solutions at intermediate salt concentration (50 mM), drop-drop collisions at lower velocity (<1 MUm) or extended time of forced drop-drop interaction exhibit a strong pull-off force of systematically varying magnitude. The observations have implications on the effects of ion-specificity and time dependence in drop-drop interactions where kinetic stability is marginal. PMID- 22309150 TI - Bifurcated hydrogen bond in lithium nitrate trihydrate probed by ab initio molecular dynamics. AB - The hydrogen-bond dynamics of lithium nitrate trihydrate has been studied by a combined approach based on ab initio molecular dynamics simulations and wavelet analysis. The simultaneous bifurcated interaction between one hydrogen atom of water molecules and two oxygen atoms of nitrate ions is the pivotal feature of the crystal structure: this bifurcated interaction has deep effects on the O-H stretching region of the vibrational spectrum. The structural, dynamic, spectroscopic, and electronic properties of the bifurcated hydrogen bond have been investigated computationally, elucidating at the molecular level the differences with weak and strong hydrogen bonds present in the crystal. These studies corroborate the very recent IR experiments performed on the lithium nitrate trihydrate crystal, offering new perspectives to interpreting the vibrational spectra. In fact, this approach allows obtaining two-dimensional plots, which summarize the essential features of both the hydrogen-bond network and IR spectra, resulting in a peculiar "signature" of the bifurcated interaction. PMID- 22309151 TI - Double sandwich polyoxometalate and its Fe(III) substituted derivative, [As2Fe5Mo21O82]17- and [As2Fe6Mo20O80(H2O)2]16-. AB - A double sandwich polyoxometalate and its Fe(III) substituted derivative, [As(2)Fe(5)Mo(21)O(82)](17-) (1) and [As(2)Fe(6)Mo(20)O(80)(H(2)O)(2)](16-) (2), were synthesized and characterized by single-crystal X-ray diffraction, infrared spectroscopy, fluorescent spectroscopy, UV spectra, thermogravimetry-differential scanning calorimetry analyses, electrospray ionization mass spectrometry, and magnetism measurements. The polyoxoanion is composed of a central fragment FeMo(7)O(28) for 1 (Fe(2)Mo(6)O(26)(H(2)O)(2) for 2) and two external AsMo(7)O(27) fragments linked together by two distinct edge-sharing dimeric clusters Fe(2)O(10) to lead to a C(2v) molecular symmetry. The central FeMo(7)O(28) fragment and external AsMo(7)O(27) fragment have a similar structure, and both of them can be viewed as a monocapped hexavacant alpha-Keggin subunit with a central FeO(4) group or a central AsO(3) group. Both of the polyoxoanions contain a oxo-bridged Fe(III)(5) magnetic core with the angles of Fe-O-Fe in the range of 96.4(4)-125.7(5) degrees , and magnetism measurements show an overall ferromagnetic interactions among the five-nuclearity cluster Fe(5) with the spin ground state S = 15/2. PMID- 22309153 TI - New pharmacologic and therapeutic approaches for hypoxic-ischemic encephalopathy in the newborn. AB - Hypoxic-ischemic encephalopathy is still an important cause of neonatal mortality and long-term disabilities. The understanding of the differential responses to hypoxia-ischemia as an initial insult leading to cellular degeneration in brain has opened the way to develop new pharmacologic and therapeutic approaches. Due to the complex pathophysiology, therapies can target early pathways such as oxidative stress, inflammation and apoptosis or delayed pathways such as the privation of growth factors and cell death. Pharmacological interventions should start at different points of time according to their mechanisms of action. The association of moderate hypothermia with neuroprotective drugs may decrease cell injury and optimize endogenous repair. More basic science research focusing on the mechanisms of injury are required. Moreover, clinical trials are needed to detect safely and effectiveness drugs and to establish the optimal time of action for each one. PMID- 22309152 TI - PRMT1 methylates the single Argonaute of Toxoplasma gondii and is important for the recruitment of Tudor nuclease for target RNA cleavage by antisense guide RNA. AB - Argonaute (Ago) plays a central role in RNA interference in metazoans, but its status in lower organisms remains ill-defined. We report on the Ago complex of the unicellular protozoan, Toxoplasma gondii (Tg), an obligatory pathogen of mammalian hosts. The PIWI-like domain of TgAgo lacked the canonical DDE/H catalytic triad, explaining its weak target RNA cleavage activity. However, TgAgo associated with a stronger RNA slicer, a Tudor staphylococcal nuclease (TSN), and with a protein Arg methyl transferase, PRMT1. Mutational analysis suggested that the N-terminal RGG-repeat domain of TgAgo was methylated by PRMT1, correlating with the recruitment of TSN. The slicer activity of TgAgo was Mg(2+)-dependent and required perfect complementarity between the guide RNA and the target. In contrast, the TSN activity was Ca(2+) -dependent and required an imperfectly paired guide RNA. Ago knockout parasites showed essentially normal growth, but in contrast, the PRMT1 knockouts grew abnormally. Chemical inhibition of Arg methylation also had an anti-parasitic effect. These results suggest that the parasitic PRMT1 plays multiple roles, and its loss affects the recruitment of a more potent second slicer to the parasitic RNA silencing complex, the exact mechanism of which remains to be determined. PMID- 22309154 TI - Robust and highly sensitive fluorescence approach for point-of-care virus detection based on immunomagnetic separation. AB - In this work, robust approach for a highly sensitive point-of-care virus detection was established based on immunomagnetic nanobeads and fluorescent quantum dots (QDs). Taking advantage of immunomagnetic nanobeads functionalized with the monoclonal antibody (mAb) to the surface protein hemagglutinin (HA) of avian influenza virus (AIV) H9N2 subtype, H9N2 viruses were efficiently captured through antibody affinity binding, without pretreatment of samples. The capture kinetics could be fitted well with a first-order bimolecular reaction with a high capturing rate constant k(f) of 4.25 * 10(9) (mol/L)(-1) s(-1), which suggested that the viruses could be quickly captured by the well-dispersed and comparable size immunomagnetic nanobeads. In order to improve the sensitivity, high luminance QDs conjugated with streptavidin (QDs-SA) were introduced to this assay through the high affinity biotin-streptavidin system by using the biotinylated mAb in an immuno sandwich mode. We ensured the selective binding of QDs-SA to the available biotin-sites on biotinylated mAb and optimized the conditions to reduce the nonspecific adsorption of QDs-SA to get a limit of detection low up to 60 copies of viruses in 200 MUL. This approach is robust for application at the point-of-care due to its very good specificity, precision, and reproducibility with an intra-assay variability of 1.35% and an interassay variability of 3.0%, as well as its high selectivity also demonstrated by analysis of synthetic biological samples with mashed tissues and feces. Moreover, this method has been validated through a double-blind trial with 30 throat swab samples with a coincidence of 96.7% with the expected results. PMID- 22309155 TI - Mohs micrographic surgery for recurrent chondroid syringoma of the eyebrow. PMID- 22309156 TI - Solving the "X" in embryos and stem cells. AB - X-chromosome inactivation (XCI) is a complex epigenetic process that ensures that most X-linked genes are expressed equally for both sexes. Female eutherian mammals inactivate randomly the maternal or paternal inherited X-chromosome early in embryogenesis, whereas the extra-embryonic tissues experience an imprinting XCI that results in the inactivation of the paternal X-chromosome in mice. Although the phenomenon was initially described 40 years ago, many aspects remain obscure. In the last 2 years, some trademark publications have shed new light on the ongoing debate regarding the timing and mechanism of imprinted or random XCI. It has been observed that XCI is not accomplished at the blastocyst stage in bovines, rabbits, and humans, contrasting with the situation reported in mice, the standard model. All the species present 2 active X-chromosomes (Xa) in the early epiblast of the blastocyst, the cellular source for embryonic stem cells (ESCs). In this perspective, it would make sense to expect an absence of XCI in undifferentiated ESCs, but human ESCs are highly heterogeneous for this parameter and the presence of 2 Xa has been proposed as a true hallmark of ground-state pluripotency and a quality marker for female ESCs. Similarly, XCI reversal in female induced pluripotent stem cells is a key reprogramming event on the path to achieve the naive pluripotency, and key pluripotency regulators can interact directly or indirectly with Xist. Finally, the presence of 2 Xa may lead to a sex specific transcriptional regulation resulting in sexual dimorphism in reprogramming and differentiation. PMID- 22309157 TI - Rapid eye movement and slow-wave sleep rebound after one night of continuous positive airway pressure for obstructive sleep apnoea. AB - BACKGROUND AND OBJECTIVE: Rebound of slow-wave sleep (SWS) and rapid eye movement (REM) sleep is observed in patients who are on continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea (OSA); but, neither have been objectively defined. The pressure titration study often represents the first recovery sleep period for patients with OSA. Our aim was to objectively define and identify predictors of SWS and REM sleep rebound following CPAP titration. METHODS: Paired diagnostic polysomnography and pressure titration studies from 335 patients were reviewed. RESULTS: The mean apnoea-hypopnoea index was 40.7 +/- 26.1, and minimum oxygen saturation was 76 +/- 14.4%. Comparing eight incremental thresholds, a rebound of 20% in REM sleep and a 40% increase in SWS allowed the best separation of prediction models. A 20% rebound in REM sleep was predicted by REM sleep %, non-REM arousal index (ArI) and total sleep time during diagnostic polysomnography, and male gender (R(2) = 35.3%). A 40% rebound in SWS was predicted by SWS %, total ArI and REM sleep % during diagnostic polysomnography, and body mass index (R(2) = 45.4%). CONCLUSIONS: A 40% rebound in SWS, but only a 20% rebound in REM sleep on the pressure titration study, is predicted by abnormal sleep architecture and sleep fragmentation prior to the commencement of treatment. PMID- 22309158 TI - Hypertrophic osteoarthropathy in Eisenmenger syndrome. AB - Hypertrophic osteoarthropathy secondary to Eisenmenger syndrome can produce severe disabling pain. We report two cases treated by intravenous pamidronate infusion with good symptomatic relief. Such therapy can greatly improve the quality of life of end-stage cyanotic congenital heart patients. PMID- 22309159 TI - Repeated cycles of chronic intermittent ethanol exposure leads to the development of tolerance to aversive effects of ethanol in C57BL/6J mice. AB - BACKGROUND: Repeated cycles of chronic intermittent ethanol (CIE) exposure lead to increased voluntary ethanol (EtOH) intake in C57BL/6J mice. This study evaluates the development of tolerance to EtOH's aversive effects in CIE exposure. METHODS: Adult male C57BL/6J mice were trained to drink 15% EtOH (vs. water) in a limited access procedure and then exposed to CIE (EtOH mice) or air (control [CTL] mice) for 5 cycles alternating with weekly access to EtOH drinking. Following the 4th CIE cycle, the aversive effects of EtOH were evaluated using a conditioned taste aversion (CTA) paradigm with 1% saccharin as the conditioned stimulus. Several doses of EtOH (0, 1, 2, and 3 g/kg) and LiCl (0.4 M, 0.02 ml/g) served as unconditioned stimuli. Finally, mice underwent a 5th CIE cycle to measure blood and brain concentrations following a 2 g/kg EtOH dose. RESULTS: CIE exposure increased EtOH drinking in EtOH mice while drinking in CTL mice remained stable. The lowest EtOH dose (1 g/kg) did not induce CTA in either group, but the highest dose (3 g/kg) produced CTA in both groups (49% reduction for CTL vs. 25% reduction for EtOH) although the group differences were not statistically significant. However, the 2 g/kg EtOH dose induced a significant aversion in CTL mice (27% reduction) but not in EtOH mice (20% increase), indicating tolerance to EtOH's aversive effects. LiCl caused a similar aversion in CTL and EtOH mice (50% reduction). Finally, blood and brain ethanol concentrations were not different between CTL and EtOH mice following a 2 g/kg EtOH dose. CONCLUSIONS: The data indicate that CIE exposure produces tolerance to the aversive effects of 2 g/kg EtOH. This effect does not appear to be related to a learning deficit or altered EtOH pharmacokinetics. These data support the notion that tolerance to EtOH's aversive effects may contribute to excessive EtOH drinking in EtOH-dependent mice. PMID- 22309160 TI - The intracarotid amobarbital procedure: when is it worth repeating? AB - PURPOSE: Despite the reported diagnostic value of the intracarotid amobarbital procedure (IAP) or "Wada test" for determining hemispheric lateralization and memory functioning, it has never undergone formal reliability testing because a prospective test-retest study design is neither feasible nor ethical. However, some patients require repeat testing for clinical purposes, a circumstance that allows for exploration of issues related to reliability. The current investigation sought to: (1) evaluate the frequency of and reasons for repeated IAPs and (2) describe the test-retest reliability of repeated IAPs in a large tertiary epilepsy center. METHODS: A 10-year review (2001-2011) of the New York University Langone Medical Center Comprehensive Epilepsy Center patient registry revealed 630 IAPs. Review of medical records identified 20 individuals who underwent two or more IAPs on separate days. Because IAPs repeated due to technical problems should be considered separate from IAPs repeated for other reasons because these IAPs likely included a change in the procedure (e.g., lower medication dose) in an attempt to ameliorate the complication, patients were grouped accordingly. Six patients underwent repeated IAPs due to technical complication and 14 patients underwent a repeated IAP due to other reasons (e.g., unexpected memory outcome, reconsideration of surgery years after a previous surgical work-up in which no surgery was performed, and/or consideration of a second surgery). Given that data obtained from injections ipsilateral to a seizure focus are sometimes considered in a manner clinically different from data obtained from injections contralateral to the seizure focus, memory outcome was classified relative to the side of identified seizure focus. The degree to which language and memory data were consistent across repeated IAPs was examined. KEY FINDINGS: Language functioning was consistently lateralized across IAPs in all but one case. Among the six patients who experienced technical problems in the first IAP, three were fully participatory in the second procedure such that valid data were obtained. For the other three, the technical problem recurred with no change in outcome across procedures. Among the 14 patients with repeated IAPs due to other reasons, 79% of the available ipsilateral and 73% of the contralateral pass/fail outcomes were consistent across procedures. No difference between ipsilateral or contralateral injections was observed for the likelihood of a change in results (p = 0.57). SIGNIFICANCE: Our data identified overall high reliability for both the ipsilateral and contralateral sides with repeated IAP testing. Results indicated that although patients for whom a correctable technical problem was identified during the IAP may benefit from a repeat study, there is little benefit to repeating the IAP in patients with discordant or unexpected results (i.e., results are not likely to change). These data support the overall reliability of both the language and memory data obtained from the IAP. PMID- 22309161 TI - Ultrabroadband light absorption by a sawtooth anisotropic metamaterial slab. AB - We present an ultrabroadband thin-film infrared absorber made of sawtoothed anisotropic metamaterial. Absorptivity of higher than 95% at normal incidence is supported in a wide range of frequencies, where the full absorption width at half maximum is about 86%. Such property is retained well at a very wide range of incident angles too. Light of shorter wavelengths are harvested at upper parts of the sawteeth of smaller widths, while light of longer wavelengths are trapped at lower parts of larger tooth widths. This phenomenon is explained by the slowlight modes in anisotropic metamaterial waveguide. Our study can be applied in the field of designing photovoltaic devices and thermal emitters. PMID- 22309162 TI - The abundance of processed pseudogenes derived from glycolytic genes is correlated with their expression level. AB - The abundance of processed pseudogenes in different vertebrate species is known to be proportional to the length of their oogenesis. However, this hypothesis cannot explain why, in a given species, certain genes produce more processed pseudogenes than others. In particular, one would expect that all genes of the glycolytic pathway would generate roughly the same number of processed pseudogenes. However, some glycolitic genes generate more processed pseudogenes than others. Here, we show that there is a positive correlation between the abundance of processed pseudogene generated from glycolytic genes and their level of expression. The variation in expression level of different glycolytic genes likely reflects the fact that some of them, such a GAPDH, have functions other than those they play in glycolysis. Furthermore, the age distribution of GAPDH processed pseudogenes corresponds to the age distribution of LINE1 elements, which are the source of the reverse transcriptase that generates processed pseudogenes. These results support the hypothesis that gene expression levels affect the level of processed pseudogene production. PMID- 22309163 TI - Air, water, and surface bacterial contamination in a university-hospital autopsy room. AB - Today, little is known about the bacteriological environment of the autopsy room and its potential interest for medico-legal practices. Seven hundred fifty microbiological samples were taken from surface (n = 660), air (n = 48), and water (n = 42) to evaluate it in a French University Forensic Department. Median bacterial counts were compared before and during autopsy for air samples, and before and after autopsy for surface samples, using Wilcoxon matched pairs signed ranks test. Bacterial identification relied on traditional phenotypic methods. Bacterial counts in the air were low before autopsy, increased significantly during procedure, and seemed more linked to the number of people in the room than to an important production of aerosol-containing bacteria. Despite cleaning, human fecal flora was omnipresent on surfaces, which revealed insufficient disinfection. Bacteriological sampling is an easy way to monitor cleaning practices in postmortem rooms, but chiefly a way to improve the reliability of medico-legal proofs of infectious deaths. PMID- 22309164 TI - Water oxidation intermediates applied to catalysis: benzyl alcohol oxidation. AB - Four distinct intermediates, Ru(IV)?O(2+), Ru(IV)(OH)(3+), Ru(V)?O(3+), and Ru(V)(OO)(3+), formed by oxidation of the catalyst [Ru(Mebimpy)(4,4' ((HO)(2)OPCH(2))(2)bpy)(OH(2))](2+) [Mebimpy = 2,6-bis(1-methylbenzimidazol-2-yl) and 4,4'-((HO)(2)OPCH(2))(2)bpy = 4,4'-bismethylenephosphonato-2,2'-bipyridine] on nanoITO (1-PO(3)H(2)) have been identified and utilized for electrocatalytic benzyl alcohol oxidation. Significant catalytic rate enhancements are observed for Ru(V)(OO)(3+) (~3000) and Ru(IV)(OH)(3+) (~2000) compared to Ru(IV)?O(2+). The appearance of an intermediate for Ru(IV)?O(2+) as the oxidant supports an O atom insertion mechanism, and H/D kinetic isotope effects support net hydride transfer oxidations for Ru(IV)(OH)(3+) and Ru(V)(OO)(3+). These results illustrate the importance of multiple reactive intermediates under catalytic water oxidation conditions and possible control of electrocatalytic reactivity on modified electrode surfaces. PMID- 22309165 TI - Intensity enhancement of weak O2 a1Deltag -> X3Sigmag(-) emission at 1270 nm by collisions with foreign gases. AB - Collision-induced near-IR emission of O(2) a(1)Delta(g) was investigated in O(2)/M (M = Ar, Kr, Xe, N(2), or CO(2)) gas mixtures, where the total pressure ranged from 10 to 100 atm, and gaseous O(2) dimol was excited with a pulsed dye laser at 630 nm through the simultaneous two-electron transition to prepare O(2) in the a(1)Delta(g) state. The a(1)Delta(g) -> X(3)Sigma(g)(-) emission intensity around 1270 nm increased with the number density of foreign gas (M) under constant O(2) number density. Emission enhancement efficiencies were in the order Xe > CO(2) > O(2) > Kr > N(2) > Ar; they are controlled by collisional enhancement during the near-IR emission at 1270 nm but not during photoabsorption at 630 nm. Efficiencies were converted into bimolecular rate constants to enhance the radiative a -> X transition for the added gases. The rate constants were estimated as quadratically dependent on the molar refraction (or polarizability) of collision gas. The self-quenching rate constant was determined from the Stern Volmer plot of the emission lifetimes measured in pure O(2). PMID- 22309166 TI - Pathogenesis and treatment concepts of orthopaedic biofilm infections. AB - Implant-associated infection is caused by surface-adhering bacteria persisting as biofilm. Periprosthetic joint infection is difficult to diagnose and treat. The high susceptibility of implanted devices to infection is because of a locally acquired host defense defect, and persistence is mainly because of the rapid formation of a biofilm resistant to host defense and antimicrobial agents. Successful treatment of periprosthetic joint infection requires the optimal surgical procedure combined with long-term antimicrobial therapy directed against surface-adhering microorganisms. Surgical treatment according to an algorithm has been validated in several observational studies. The role of rifampin against device-associated staphylococcal infection has been evaluated in an animal model, in observational studies and in a controlled trial. Given the limited efficacy of traditional antibiotics in implant-associated infections, novel strategies such as coating of the device, vaccination against biofilms, and quorum-sensing inhibitors are promising future options for prevention and treatment. PMID- 22309167 TI - Directed self-assembly of colloidal crystals by dielectrophoretic ordering. AB - In this Article, we report the dielectrophoretic assembly of colloidal particles and show how the kinetics of assembly and degree of ordering depend on the particle size, charge, solution ionic strength, and field strength and frequency. A special dielectrophoresis (DEP) sample cell is constructed and validated to quantitatively measure directed self-assembly via sequential light scattering and optical microscopy measurements. Our results confirm the recently established scaling for the order-disorder transition and extend it to higher scaled frequencies. The limiting scaling of the order-disorder transition and particle electrophoretic mobility are correctly predicted by the standard electrokinetic model (SEKM). In particular, the order-disorder transition line is predicted from the particle properties using a recently proposed empirical scaling law and the SEKM over an order of magnitude in particle size. PMID- 22309168 TI - Readthrough of long-QT syndrome type 1 nonsense mutations rescues function but alters the biophysical properties of the channel. AB - The nonsense mutations R518X-KCNQ1 and Q530X-KCNQ1 cause LQT1 (long-QT syndrome type 1) and result in a complete loss of I(Ks) channel function. In the present study we attempted to rescue the function of these mutants, in HEK (human embryonic kidney)-293 cells, by promoting readthrough of their PTCs (premature termination codons) using the pharmacological agents G-418, gentamicin and PTC124. Gentamicin and G-418 acted to promote full-length channel protein expression from R518X at 100 MUM and from Q530X at 1 mM. In contrast, PTC124 did not, at any dose tested, induce readthrough of either mutant. G-418 (1 mM) treatment also acted to significantly (P<0.05) increase current density and peak tail current density, at +80 mV for R518X, but not Q530X, to 58+/-11% and 82+/ 17% of the wild-type level respectively. However, the biophysical properties of the currents produced from R518X, while similar, were not identical with wild type as the voltage-dependence of activation was significantly (P<0.05) shifted by +25 mV. Overall, these findings indicate that although functional rescue of LQT1 nonsense mutations is possible, it is dependent on the degree of readthrough achieved and the effect on channel function of the amino acid substituted for the PTC. Such considerations will determine the success of future therapies. PMID- 22309169 TI - Synthesis and biological properties of highly sequence-specific-alkylating N methylpyrrole-N-methylimidazole polyamide conjugates. AB - Four new alkylating N-methylpyrrole-N-methylimidazole (PI) polyamide conjugates (1-4) with seven-base-pair (bp) recognition ability were synthesized. Evaluation of their DNA-alkylating activity clearly showed accurate alkylation at match site(s). The cytotoxicities of conjugates 1-4 were determined against six human cancer cell lines, and the effect of these conjugates on the expression levels of the whole human genome in A549 cells were also investigated. A few genes among the top 20 genes were commonly downregulated by each conjugate, which reflects their sequence specificity. Conversely, many of the top 10 genes were commonly upregulated, which may have been caused by alkylation damage to DNA. Moreover, the antitumor activities of the PI polyamide conjugates 2 and 3 were investigated using nude mice transplanted with DU145 or A549. The intravenous administration of each liposomal conjugate in water yielded tumor-suppressing effects specifically toward DU145 cells and not A549 cells, which was pertinent to cytotoxicity. PMID- 22309171 TI - TCM active ingredient oxoglaucine metal complexes: crystal structure, cytotoxicity, and interaction with DNA. AB - The alkaloid oxoglaucine (OG), which is a bioactive component from traditional Chinese medicine (TCM), was synthesized by a two-step reaction and used as the ligand to react with transition metal salts to give four complexes: [OGH][AuCl(4)].DMSO (1), [Zn(OG)(2)(H(2)O)(2)](NO(3))(2) (2), [Co(OG)(2)(H(2)O)(2)](ClO(4))(2) (3), and [Mn(OG)(2)(H(2)O)(2)](ClO(4))(2) (4). The crystal structures of the metal complexes were confirmed by single crystal X ray diffraction. Complex 1 is an ionic compound consisting of a charged ligand [OGH](+) and a gold complex [AuCl(4)](-). Complexes 2-4 all have similar structures (inner-spheres), that is, octahedral geometry with two OG coordinating to one metal center and two aqua ligands occupying the two apical positions of the octahedron, and two NO(3)(-) or ClO(4)(-) as counteranions in the outer sphere. The complexation of OG to metal ion was confirmed by ESI-MS, capillary electrophoresis and fluorescence polarization. The in vitro cytotoxicity of these complexes toward a various tumor cell lines was assayed by the MTT method. The results showed that most of these metal-oxoglaucine complexes exhibited enhanced cytotoxicity compared with oxoglaucine and the corresponding metal salts, with IC(50) values ranging from 1.4 to 32.7 MUM for sensitive cancer cells, which clearly implied a positive synergistic effect. Moreover, these complexes appeared to be selectively active against certain cell lines. The interactions of oxoglaucine and its metal complexes with DNA and topoisomerase I were investigated by UV-vis, fluorescence, CD spectroscopy, viscosity, and agarose gel electrophoresis, and the results indicated that these OG-metal complexes interact with DNA mainly via intercalation. Complexes 2-4 are metallointercalators, but complex 1 is not. These metal complexes could effectively inhibit topoisomerase I even at low concentration. Cell cycle analysis revealed that 1-3 caused S-phase cell arrest. PMID- 22309170 TI - Structures of (5'S)-8,5'-Cyclo-2'-deoxyguanosine Mismatched with dA or dT. AB - Diastereomeric 8,5'-cyclopurine 2'-deoxynucleosides, containing a covalent bond between the deoxyribose and the purine base, are induced in DNA by ionizing radiation. They are suspected to play a role in the etiology of neurodegeneration in xeroderma pigmentosum patients. If not repaired, the S-8,5'-cyclo-2' deoxyguanosine lesion (S-cdG) induces Pol V-dependent mutations at a frequency of 34% in Escherichia coli. Most are S-cdG -> A transitions, suggesting mis incorporation of dTTP opposite the lesion during replication bypass, although low levels of S-cdG -> T transversions, arising from mis-incorporation of dATP, are also observed. We report the structures of 5'-d(GTGCXTGTTTGT)-3'.5' d(ACAAACAYGCAC)-3', where X denotes S-cdG and Y denotes either dA or dT, corresponding to the situation following mis-insertion of either dTTP or dATP opposite the S-cdG lesion. The S-cdG.dT mismatch pair adopts a wobble base pairing. This provides a plausible rationale for the S-cdG -> A transitions. The S-cdG.dA mismatch pair differs in conformation from the dG.dA mismatch pair. For the S-cdG.dA mismatch pair, both S-cdG and dA intercalate, but no hydrogen bonding is observed between S-cdG and dA. This is consistent with the lower levels of S-cdG -> T transitions in E. coli. PMID- 22309172 TI - The effect of implant size 5 * 8 mm on crestal bone levels around single-tooth implants. AB - BACKGROUND: There is substantial evidence supporting the strain-induced biologic response of bone to mechanical load. Stress-related factors, such as implant size, have been associated with changes in crestal bone levels on dental implants. The purpose of this study is to evaluate the effect of an implant size, specifically 5 mm wide * 8 mm long (5 * 8), on peri-implant bone levels. METHODS: A retrospective cohort study was conducted. The cohort was composed of patients who had >=1 plateau root-form implant. Descriptive statistics, univariate and multivariate mixed-effects regression models, adjusted for multiple implants in the same patient were used to evaluate the correlation between 5 * 8 implants and other clinically relevant factors on crestal bone levels after insertion of single-tooth replacements. RESULTS: The cohort was composed of 81 individuals who received 326 implants. The average change in crestal bone levels (AvBL) for 5 * 8 maxillary and mandibular implants after 5.9 years of follow-up were -0.36 and 0.04 mm, respectively. In contrast, AvBL for mandibular implants not measuring 5 * 8 was -0.51 mm. Of several different local and systemic factors evaluated, including 10 different implant sizes, 5 * 8 mandibular implants were found to be significantly less likely to lose bone when compared with mandibular implants not measuring 5 * 8 (P = 0.047). CONCLUSIONS: Implants measuring 5 * 8 demonstrated statistically significantly less peri-implant bone loss in the posterior mandible. This finding indicated that a specific implant size may be involved in mandibular bone preservation. However, prospective multicenter clinical trials are needed to validate these findings. PMID- 22309173 TI - Depot medroxyprogesterone acetate use and periodontal health in 15- to 44-year old US females. AB - BACKGROUND: It has been suggested that progestins may have an inflammatory component and/or increase in prostaglandin synthesis. Thus, extended progestin use may be associated with higher risk of periodontal diseases. This study investigates the association between depot medroxyprogesterone acetate (DMPA) injectable contraception and the prevalence of periodontal diseases among US premenopausal females. METHODS: Data for this cross-sectional analysis comes from the 1999 to 2004 National Health and Nutrition Examination Surveys. This analysis includes 4,460 US females (15 to 44 years of age) with complete DMPA usage and periodontal status data. RESULTS: Current and past DMPA use was 4.1% and 12.0%, respectively. The prevalence of gingivitis was 53.9% for females who reported having used DMPA compared with 46.1% for DMPA never-users. Females taking DMPA were more likely to be young, single, and non-white, have a history of smoking, have lower levels of education and income, and have >=1 live births and were less likely to visit the dentist. Using logistic regression, DMPA use was associated with an increased risk of gingivitis (odds ratio [OR] =1.7; 95% confidence interval [CI] = 1.09 to 1.67) and periodontitis (DMPA, OR = 1.49; 95% CI = 1.01 to 2.22) after adjusting for age, race, education, poverty income ratio, dental care use, and smoking status. A significant interaction between smoking status and DMPA use was also found (P = 0.029). CONCLUSIONS: This study suggests that DMPA use may be associated with periodontal diseases. Additional investigation is warranted as a result of the disproportionate usage of DMPA among low-income populations who are at an increased risk for poor dental health. PMID- 22309174 TI - Influence of thread design on implant positioning in immediate implant placement. AB - BACKGROUND: It is generally believed that implants placed in extraction sockets have a tendency to shift in the facial direction during insertion. The purpose of this study is to investigate the effect of different thread designs on the final implant position in immediate implant placement. METHODS: In a split-mouth design involving 11 cadaver heads, each specimen received two implants, one with a square and one with a V-shaped thread design, in maxillary incisor extraction sockets. The facio-lingual locations of the drills and the implant were tracked, and the displacements were compared between the two groups. RESULTS: No statistically significant differences were observed between the square and V shaped thread design groups. The mean displacements of the different groups showed a general tendency of the implants to be positioned facially compared with the initial drill trajectory. This tendency was greater for implants with square thread design. CONCLUSION: There was no significant effect of implant thread design on the positioning of implants in extraction sockets. PMID- 22309175 TI - Periodontitis as a risk factor for preeclampsia. AB - BACKGROUND: Periodontitis is an inflammatory process caused by a specific group of microorganisms, resulting in the destruction of the tooth-supporting tissue and the resorption of the alveolar bone. Therefore, periodontitis has been considered a risk factor for preeclampsia because infection is one of the factors involved in the etiology and pathogenesis of preeclampsia. The aim of the present study is to determine whether periodontitis is a risk factor for preeclampsia and to identify other possible risk factors. METHODS: A case-control study was performed with 574 puerperae under care at the university hospital at the Universidade Federal de Pernambuco in the city of Recife, Brazil. Data collection was preceded by a training exercise and a pilot study. Biologic and socioeconomic data were collected along with medical and dental records. A periodontal examination was performed on all dental elements to determine probing depth and gingival recession. The association between periodontitis and preeclampsia was first adjusted for the variables within each block, and adjusted for the variables of all blocks in the final multivariate model. RESULTS: The multivariate logistic regression analysis showed that, after adjustment for other risk factors, periodontitis remained an independent risk factor for preeclampsia (adjusted odds ratio [OR] = 8.60, confidence interval [CI] = 3.92 to 18.88, P < 0.001 and adjusted OR = 2.03, 95% CI = 1.43 to 2.90, P < 0.001, when using the Centers for Disease Control and Prevention/American Academy of Periodontology definition). CONCLUSION: The results suggest that within the population studied, periodontitis was a risk factor for preeclampsia. PMID- 22309176 TI - Diabetes mellitus may increase bone loss after occlusal trauma and experimental periodontitis. AB - BACKGROUND: Diabetes mellitus (DM) involves metabolic changes that can negatively influence periodontal tissues, resulting in more prevalent and severe periodontitis and impaired bone formation. Occlusal trauma (OT) is an injury of the supportive periodontium that results in bone loss. It can be hypothesized that DM would increase bone loss after OT, mainly when associated with periodontitis. Thus, the aim of the present study is to evaluate the influence of DM on bone response in the furcation area of teeth subjected to OT in the presence, or absence, of experimental periodontitis (EP) in the rat model. METHODS: Thirty-two male Wistar rats were assigned to four groups: 1) group 1 (G1): DM+OT+EP (n = 8); 2) group 2 (G2): DM+OT (n = 8); 3) group 3 (G3): OT+EP (n = 8); and 4) group 4 (G4): OT (n = 8). G1 and G2 received a single intraperitoneal injection of streptozotocin (STZ). After 10 days, G1 and G3 were subjected to EP by ligature placement. Fifteen days after the start of EP, OT was induced by the creation of a premature contact. The animals were euthanized 35 days after DM induction. RESULTS: DM enhanced bone loss in the presence of OT combined with EP, but did not increase bone loss in teeth subjected to OT alone. EP caused greater bone loss when associated with OT. CONCLUSION: Within the limits of this animal study, it can be concluded that DM enhances bone loss in the presence of occlusal trauma associated with EP. PMID- 22309177 TI - The effect of supra- and subphysiologic testosterone levels on ligature-induced bone loss in rats--a radiographic and histologic pilot study. AB - BACKGROUND: Testosterone is the primary male sexual hormone, and varying concentrations of the hormone mediated by physiologic, pathologic, or pharmacologic mechanisms may induce large variations in the body. Data regarding the general role of testosterone in mediating inflammation are still inconclusive. Therefore, the purpose of this study is to assess the consequences of supra- and subphysiologic levels of testosterone on ligature-induced bone loss in rats. METHODS: Three male adult Holtzman rats were used to observe the course of serum testosterone concentration following orchiectomy (Ocx) and testosterone injections. Another 60 rats were randomly assigned to the following groups: (1) sham-operation controls (n = 10); (2) sham-operation and ligature-induced bone loss (n = 10); (3) orchiectomy without ligature (Ocx; n = 10); (4) Ocx and ligature (n = 10); (5) Ocx plus 250 mg/kg body weight intramuscular testosterone esters injection without ligature (Ocx+T; n = 10); and (6) Ocx, T, and ligature (n = 10). The ligatures were placed 30 days postorchiectomy (or sham-operation) and maintained for 15 days. Thereafter, the rats were sacrificed, and their hemimandibles were used for radiographic evaluation of bone loss along with histologic and histometric analyses of gingival tissue. RESULTS: The results indicated a significant increase in bone loss in the Ocx and Ocx+T groups in the presence and absence of inflammation, respectively. In addition, the Ocx and Ocx+T groups presented increased gingival area accompanying ligature-induced bone loss. CONCLUSIONS: Both sub- and supraphysiologic testosterone levels may influence bone metabolism, but only subphysiologic levels significantly increase ligature-induced bone loss. Moreover, testosterone has a regulatory effect on the gingival area. PMID- 22309178 TI - A comparative evaluation of the antibacterial efficacy of honey in vitro and antiplaque efficacy in a 4-day plaque regrowth model in vivo: preliminary results. AB - BACKGROUND: Honey has a potent broad-spectrum antibacterial action that may make it suitable for "anti-infective" treatment of periodontal disease. The aims of this study are as follows: 1) to evaluate the antibacterial efficacy of honey against oral bacteria and compare the same with 0.2% chlorhexidine; and 2) to compare antiplaque efficacy in vivo with chlorhexidine. METHODS: The study was conducted in two parts. In the in vitro part, the inhibitory effects of three test agents, 0.2% chlorhexidine gluconate, honey mouthwash, and saline, against six oral bacteria at concentrations of 1, 2, 4, 8, 16, 32, 64, 128, 256, and 512 MUg/mL were tested in duplicate. The minimum inhibitory concentration (MIC) was set as the lowest concentration of the agent that completely inhibited the growth of the test species. The in vivo part consisted of a double-masked parallel clinical trial based on a 4-day plaque regrowth model. Sixty-six volunteers, 20 to 24 years of age, participated in the study, and the plaque scores were compared at baseline and at the end of 4 days. The Kruskal-Wallis test was used for significance, and the Mann-Whitney U test was used for pairwise comparison of the groups. The mean plaque scores were 1.77 +/- 0.86, 1.64 +/- 0.90, and 3.27 +/ 0.83 for groups 1, 2, and 3, respectively. RESULTS: The honey mouthrinse effectively inhibited the six tested microorganisms. The chlorhexidine gluconate rinse had the lowest MICs compared with honey and saline rinses for all test species examined. The in vivo results revealed that plaque formation was inhibited/reduced by chlorhexidine and honey rinses. CONCLUSION: Honey has antibacterial action against tested oral microorganisms and also has antiplaque action. PMID- 22309179 TI - Treatments for anxiety and depression in patients with chronic obstructive pulmonary disease: a literature review. AB - Chronic obstructive pulmonary disease (COPD) is a serious contemporary health issue. Psychological co-morbidities such as anxiety and depression are common in COPD. Current evidence for treatment options to reduce anxiety and depression in patients with COPD was examined. There is evidence available for the efficacy of pharmacological treatments, cognitive behavioural therapy, pulmonary rehabilitation, relaxation therapy and palliative care in COPD. Therapeutic modalities that have not been proven effective in decreasing anxiety and depression in COPD, but which have theoretical potential among patients, include interpersonal psychotherapy, self-management programmes, more extensive disease management programmes, supportive therapy and self-help groups. Besides pulmonary rehabilitation that is only available for a small percentage of patients, management guidelines make scant reference to other options for the treatment of mental health problems. The quantity and quality of research on mental health treatments in COPD have historically been insufficient to support their inclusion in COPD treatment guidelines. In this review, recommendations regarding assessment, treatment and future research in this important field were made. PMID- 22309180 TI - Mechanisms of Trypanosoma cruzi persistence in Chagas disease. AB - Trypanosoma cruzi infection leads to development of chronic Chagas disease. In this article, we provide an update on the current knowledge of the mechanisms employed by the parasite to gain entry into the host cells and establish persistent infection despite activation of a potent immune response by the host. Recent studies point to a number of T. cruzi molecules that interact with host cell receptors to promote parasite invasion of the diverse host cells. T. cruzi expresses an antioxidant system and thromboxane A(2) to evade phagosomal oxidative assault and suppress the host's ability to clear parasites. Additional studies suggest that besides cardiac and smooth muscle cells that are the major target of T. cruzi infection, adipocytes and adipose tissue serve as reservoirs from where T. cruzi can recrudesce and cause disease decades later. Further, T. cruzi employs at least four strategies to maintain a symbiotic-like relationship with the host, and ensure consistent supply of nutrients for its own survival and long-term persistence. Ongoing and future research will continue to help refining the models of T. cruzi invasion and persistence in diverse tissues and organs in the host. PMID- 22309181 TI - Basal cell carcinoma of the scrotum: clinicopathologic analysis of 10 cases. AB - BACKGROUND: Basal cell carcinoma (BCC) located on the scrotum is rare. OBJECTIVE: To analyze clinical and pathologic features, discuss therapeutic strategies, and identify prognostic factors of scrotal BCC in Chinese patients. MATERIALS AND METHODS: Between 2000 and 2010, 10 patients with scrotal BCC were diagnosed and treated at our institution. A review was performed using the clinical records and dermatopathologic slides of these patients. RESULTS: The median patient age was 70. Skin lesions presented as red nodules and brownish plaques. All patients were treated using wide excision without adjuvant therapy. After an average follow-up of 47 months, eight patients were in good health without any relapse. One patient developed left inguinal lymph node metastasis at 21 months that was successfully treated using bilateral inguinal lymphadenectomy. One patient developed bilateral pulmonary metastasis at 48 months and was palliatively treated with chemotherapy. The clinical and histopathologic risk factors predisposing to metastasis were large primary neoplasms; a long period of misdiagnosis; and infiltrating, morpheaform, spiky, irregular outline pathologic patterns. CONCLUSIONS: BCC of the scrotum is rare. It can metastasize after a long period of initial therapy. Long-term surveillance including a complete metastatic examination is recommended for these patients. PMID- 22309183 TI - Exsanguinated blood volume estimation using fractal analysis of digital images. AB - The estimation of bloodstain volume using fractal analysis of digital images of passive blood stains is presented. Binary digital photos of bloodstains of known volumes (ranging from 1 to 7 mL), dispersed in a defined area, were subjected to image analysis using FracLac V. 2.0 for ImageJ. The box-counting method was used to generate a fractal dimension for each trial. A positive correlation between the generated fractal number and the volume of blood was found (R(2) = 0.99). Regression equations were produced to estimate the volume of blood in blind trials. An error rate ranging from 78% for 1 mL to 7% for 6 mL demonstrated that as the volume increases so does the accuracy of the volume estimation. This method used in the preliminary study proved that bloodstain patterns may be deconstructed into mathematical parameters, thus removing the subjective element inherent in other methods of volume estimation. PMID- 22309182 TI - Adenosine and glutamate signaling in neuron-glial interactions: implications in alcoholism and sleep disorders. AB - Recent studies have demonstrated that the function of glia is not restricted to the support of neuronal function. Especially, astrocytes are essential for neuronal activity in the brain. Astrocytes actively participate in synapse formation and brain information processing by releasing or uptaking gliotransmitters such as glutamate, d-serine, adenosine 5'-triphosphate (ATP), and adenosine. In the central nervous system, adenosine plays an important role in regulating neuronal activity as well as in controlling other neurotransmitter systems such as GABA, glutamate, and dopamine. Ethanol (EtOH) increases extracellular adenosine levels, which regulates the ataxic and hypnotic/sedative (somnogenic) effects of EtOH. Adenosine signaling is also involved in the homeostasis of major inhibitory/excitatory neurotransmission (i.e., GABA or glutamate) through neuron-glial interactions, which regulates the effect of EtOH and sleep. Adenosine transporters or astrocytic SNARE-mediated transmitter release regulates extracellular or synaptic adenosine levels. Adenosine then exerts its function through several adenosine receptors and regulates glutamate levels in the brain. This review presents novel findings on how neuron-glial interactions, particularly adenosinergic signaling and glutamate uptake activity involving glutamate transporter 1 (GLT1), are implicated in alcoholism and sleep disorders. PMID- 22309184 TI - Type B interrupted left aortic arch with isolated right subclavian artery. AB - Interrupted aortic arch is a rare congenital heart malformation occurring in approximately three per 1 million births. Type B interrupted aortic arch (interruption between the second carotid artery and the ipsilateral subclavian artery) is the most common of three major types (A, B, and C). We report an extremely rare finding: a case of left-sided type B interrupted aortic arch with isolation of the right subclavian artery (origin from the right pulmonary artery). PMID- 22309185 TI - Ultrafast intramolecular exciton splitting dynamics in isolated low-band-gap polymers and their implications in photovoltaic materials design. AB - Record-setting organic photovoltaic cells with PTB polymers have recently achieved ~8% power conversion efficiencies (PCE). A subset of these polymers, the PTBF series, has a common conjugated backbone with alternating thieno[3,4 b]thiophene and benzodithiophene moieties but differs by the number and position of pendant fluorine atoms attached to the backbone. These electron-withdrawing pendant fluorine atoms fine tune the energetics of the polymers and result in device PCE variations of 2-8%. Using near-IR, ultrafast optical transient absorption (TA) spectroscopy combined with steady-state electrochemical methods we were able to obtain TA signatures not only for the exciton and charge separated states but also for an intramolecular ("pseudo") charge-transfer state in isolated PTBF polymers in solution, in the absence of the acceptor phenyl C(61)-butyric acid methyl ester (PCBM) molecules. This led to the discovery of branched pathways for intramolecular, ultrafast exciton splitting to populate (a) the charge-separated states or (b) the intramolecular charge-transfer states on the subpicosecond time scale. Depending on the number and position of the fluorine pendant atoms, the charge-separation/transfer kinetics and their branching ratios vary according to the trend for the electron density distribution in favor of the local charge-separation direction. More importantly, a linear correlation is found between the branching ratio of intramolecular charge transfer and the charge separation of hole-electron pairs in isolated polymers versus the device fill factor and PCE. The origin of this correlation and its implications in materials design and device performance are discussed. PMID- 22309186 TI - Comparative proteomic analysis of auxin-induced embryogenic and nonembryogenic tissues of the solanaceous tree Cyphomandra betacea (Tamarillo). AB - Cyphomandra betacea (tamarillo) is a tree that produces edible, highly nutritional fruits. In tamarillo, somatic embryogenesis (SE) is achieved through a two-step process starting with the formation of an embryogenic tissue on an auxin-rich medium and further development of embryos, following tissue transfer to an auxin-free medium. During the induction stage, both embryogenic (EC) and nonembryogenic calli (NEC) arise from the same explant (immature leaves or mature zygotic embryos) in the presence of either picloram or 2,4-dichlorophenoxyacetic acid. In an attempt to find somatic embryogenic-specific proteins, a comparative analysis of the proteome of tamarillo's EC and NEC was performed. Analysis of 2 DE gels revealed ca. 150 differentially expressed proteins, from which 22 have been identified by LC-MS/MS. Proteins exclusively or predominantly expressed in EC included metabolism-related proteins, such as enolases or treonine synthases, and also heat-shock and ribosomal proteins. Pathogenesis-related proteins were found mainly in NEC. A number of additional differentially expressed proteins involved in various functional categories were also identified. A quantitative real time PCR (qPCR) analysis revealed no significant differences at the mRNA level for 11 differentially expressed proteins, with exception of the pathogenesis-related proteins that were up-regulated in NEC. This seems to indicate that a posttranscriptional control might be responsible for the proteomic differences detected. PMID- 22309187 TI - Protective role of alpha-galactosylceramide-stimulated natural killer T cells in genital tract infection with Chlamydia muridarum. AB - Natural killer T (NKT) cells are a unique lymphocyte subpopulation which has an important role in the response to microbial pathogens. In this study, we used alpha-galactosylceramide (alpha-GalCer), a specific ligand of NKT cells, to enhance NKT response and examine its effect on host defense against genital tract Chlamydia muridarum infection. The results showed that alpha-GalCer treatment before infection led to reduced pathological changes and bacterial burden in the genital tract. Moreover, alpha-GalCer-treated mice showed greater local Th1 cytokine production [interferon gamma (IFN-gamma) and interleukin 12 (IL-12)] in local lymph node cells and genital tissues following challenge infection compared with untreated mice, as well as an enhanced level of IFN-gamma production by NK and T cells. In addition, NKT cells in the mice with genital tract C. muridarum infection, unlike those from naive mice, showed a polarized IFN-gamma production. These results suggest a promoting role of NKT cells on type 1 T cell immune response and host resistance to Chlamydia in genital tract infection. PMID- 22309188 TI - Small peptide inhibitors of acetyl-peptide hydrolase having an uncommon mechanism of inhibition and a stable bent conformation. AB - Acyl peptide hydrolase (APEH) catalyzes the removal of acetyl-amino acids from the N-terminus of peptides and cytoplasmic proteins. Due to the role played in several diseases, and to the growing interest around N-terminal acetylation, studies on APEH structure, function, and inhibition are attracting an ever increasing attention. We have therefore screened a random tetrapeptide library, N capped with selected groups, and identified a trifluoroacetylated tetrapeptide (CF(3)-lmph) which inhibits the enzyme with a K(i) of 24.0 +/- 0.8 MUM. The inhibitor is selective for APEH, shows an uncommon uncompetitive mechanism of inhibition, and in solution adopts a stable bent conformation. CF(3)-lmph efficiently crosses cell membranes, blocking the cytoplasmic activity of APEH; however, it triggers a mild pro-apoptotic effect as compared to other competitive and noncompetitive inhibitors. The unusual inhibition mechanism and the stable structure make the new compound a novel tool to investigate enzyme functions and a useful scaffold to develop more potent inhibitors. PMID- 22309189 TI - Combinatorial human progenitor cell transplantation optimizes islet regeneration through secretion of paracrine factors. AB - Transplanted human bone marrow (BM) and umbilical cord blood (UCB) progenitor cells activate islet-regenerative or revascularization programs depending on the progenitor subtypes administered. Using purification of multiple progenitor subtypes based on a conserved stem cell function, high aldehyde dehydrogenase (ALDH) activity (ALDH(hi)), we have recently shown that transplantation of BM derived ALDH(hi) progenitors improved systemic hyperglycemia and augmented insulin secretion by increasing islet-associated proliferation and vascularization, without increasing islet number. Conversely, transplantation of culture-expanded multipotent-stromal cells (MSCs) derived from BM ALDH(hi) cells augmented total beta cell mass via formation of beta cell clusters associated with the ductal epithelium, without sustained islet vascularization. To identify paracrine effectors produced by islet-regenerative MSCs, culture-expanded BM ALDH(hi) MSCs were transplanted into streptozotocin-treated nonobese diabetic/severe combine immune deficient (SCID) mice and segregated into islet regenerative versus nonregenerative cohorts based on hyperglycemia reduction, and subsequently compared for differential production of mRNA and secreted proteins. Regenerative MSCs showed increased expression of matrix metalloproteases, epidermal growth factor receptor (EGFR)-activating ligands, and downstream effectors of Wnt signaling. Regenerative MSC supernatant also contained increased levels of pro-angiogenic versus pro-inflammatory cytokines, and augmented the expansion of ductal epithelial but not beta cells in vitro. Conversely, co culture with UCB ALDH(hi) cells induced beta cell but not ductal epithelial cell proliferation. Sequential transplantation of MSCs followed by UCB ALDH(hi) cells improved hyperglycemia and glucose tolerance by increasing beta cell mass associated with the ductal epithelium and by augmenting intra-islet capillary densities. Thus, combinatorial human progenitor cell transplantation stimulated both islet-regenerative and revascularization programs. Understanding the progenitor-specific pathways that modulate islet-regenerative and revascularization processes may provide new approaches for diabetes therapy. PMID- 22309190 TI - ZnO/Cu nanocomposite: a platform for direct electrochemistry of enzymes and biosensing applications. AB - Unique structured nanomaterials can facilitate the direct electron transfer between redox proteins and the electrodes. Here, in situ directed growth on an electrode of a ZnO/Cu nanocomposite was prepared by a simple corrosion approach, which enables robust mechanical adhesion and electrical contact between the nanostructured ZnO and the electrodes. This is great help to realize the direct electron transfer between the electrode surface and the redox protein. SEM images demonstrate that the morphology of the ZnO/Cu nanocomposite has a large specific surface area, which is favorable to immobilize the biomolecules and construct biosensors. Using glucose oxidase (GOx) as a model, this ZnO/Cu nanocomposite is employed for immobilization of GOx and the construction of the glucose biosensor. Direct electron transfer of GOx is achieved at ZnO/Cu nanocomposite with a high heterogeneous electron transfer rate constant of 0.67 +/- 0.06 s(-1). Such ZnO/Cu nanocomposite provides a good matrix for direct electrochemistry of enzymes and mediator-free enzymatic biosensors. PMID- 22309191 TI - Glyoxylate reductase isoform 1 is localized in the cytosol and not peroxisomes in plant cells. AB - Glyoxylate reductase (GLYR) is a key enzyme in plant metabolism which catalyzes the detoxification of both photorespiratory glyoxylate and succinic semialdehdye, an intermediate of the gamma-aminobutyrate (GABA) pathway. Two isoforms of GLYR exist in plants, GLYR1 and GLYR2, and while GLYR2 is known to be localized in plastids, GLYR1 has been reported to be localized in either peroxisomes or the cytosol. Here, we reappraised the intracellular localization of GLYR1 in Arabidopsis thaliana L. Heynh (ecotype Lansberg erecta) using both transiently transformed suspension cells and stably-transformed plants, in combination with fluorescence microscopy. The results indicate that GLYR1 is localized exclusively to the cytosol regardless of the species, tissue and/or cell type, or exposure of plants to environmental stresses that would increase flux through the GABA pathway. Moreover, the C-terminal tripeptide sequence of GLYR1, -SRE, despite its resemblance to a type 1 peroxisomal targeting signal, is not sufficient for targeting to peroxisomes. Collectively, these results define the cytosol as the intracellular location of GLYR1 and provide not only important insight to the metabolic roles of GLYR1 and the compartmentation of the GABA and photorespiratory pathways in plant cells, but also serve as a useful reference for future studies of proteins proposed to be localized to peroxisomes and/or the cytosol. PMID- 22309192 TI - An intraoperative multimodal neurophysiologic approach to successful resection of precentral gyrus epileptogenic lesions. AB - Cortical dysplasias (CDs) are highly epileptogenic lesions with a good prognosis of seizure freedom, if totally resected. However, their accurate delineation and resection can be difficult, and depend on the extent of pathology and lesion location. Intraoperative neurophysiologic assessments are valuable in these situations. We present an illustrative case of intractable epilepsy where judicious use of intraoperative neurophysiologic-techniques guided resection of precentral CD, under general anesthesia and in the absence of preoperative electrophysiologic mapping data. Ictal onset was accurately delineated using electrocorticography (ECoG). Phase reversal of the median somatosensory-evoked potentials (MSSEPs) localized the central sulcus (CS). Motor evoked potentials (MEPs) triggered by high-frequency monopolar anodal electrical cortical stimulation at the primary motor cortex (PMC) threshold delineated the PMC. Using this technique, PMC and the corticospinal tract (CST) were continuously monitored during resection. No changes in MEPs from the preresection baseline were seen; no residual abnormal activity was present in the postresection ECoG. The patient emerged from surgery without deficits and has been seizure free during a 10-month follow-up. Staged multimodal intraoperative neurophysiology can be used successfully under general anesthesia to guide resection of epileptogenic lesions within the precentral gyrus, as an add-on or, in certain situations, as a viable alternative to preoperative electrophysiologic mapping. PMID- 22309194 TI - Influencing the size and anion selectivity of dimeric Ln(3+)[15-metallacrown-5] compartments through systematic variation of the host side chains and central metal. AB - Dimeric Ln(3+)[15-metallacrown-5] compartments selectively recognize carboxylates through guest binding to host metal ions and intermolecular interactions with the phenyl side chains. A systematic study is presented on how the size, selectivity, and number of encapsulated guests in the dimeric containers is influenced by the Ln(3+)[15-metallacrown(Cu(II))-5] ligand side chain and central metal. Compartments of varying heights were assembled from metallacrowns with S phenylglycine hydroxamic acid (pgHA), S-phenylalanine hydroxamic acid (pheHA), and S-homophenylalanine hydroxamic acid (hpheHA) ligands. Guests that were examined include the fully deprotonated forms of terephthalic acid, isonicotinic acid, and bithiophene dicarboxylic acid (btDC). X-ray crystallography reveals that the side-chain length constrains the maximum and minimum length guest that can be encapsulated in the compartment. Compartments with heights ranging from 9.7 to 15.2 A are formed with different phenyl side chains that complex 4.3-9.2 A long guests. Up to five guests are accommodated in Ln(3+)[15-metallacrown(Cu(II)) 5] compartments depending on steric effects from the host side chains. The nine coordinate La(3+) central metal promotes the encapsulation of multiple guests, while the eight-coordinate Gd(3+) typically binds only one dicarboxylate. Electrospray ionization mass spectrometry reveals that the dimerization phenomenon occurs beyond the solid state, suggesting that these containers can be utilized in solid-state and solution applications. PMID- 22309193 TI - Mechanism and specificity of the human paracaspase MALT1. AB - The paracaspase domain of MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1) is a component of a gene translocation fused to the N terminal domains of the cellular inhibitor of apoptosis protein 2. The paracaspase itself, commonly known as MALT1, participates in the NF-kappaB (nuclear factor kappaB) pathway, probably by driving survival signals downstream of the B-cell antigen receptor through MALT1 proteolytic activity. We have developed methods for the expression and purification of recombinant full-length MALT1 and its constituent catalytic domain alone. Both are activated by dimerization without cleavage, with a similar dimerization barrier to the distantly related cousins, the apical caspases. By using positional-scanning peptidyl substrate libraries we demonstrate that the activity and specificity of full-length MALT1 is recapitulated by the catalytic domain alone, showing a stringent requirement for cleaving after arginine, and with striking peptide length constraints for efficient hydrolysis. Rates of cleavage (kcat/Km values) of optimal peptidyl substrates are in the same order (10(3)-10(4) M(-1).s(-1)) as for a putative target protein CYLD. Thus MALT1 has many similarities to caspase 8, even cleaving the putative target protein CYLD with comparable efficiencies, but with diametrically opposite primary substrate specificity. PMID- 22309195 TI - Radiolabeled absorption, distribution, metabolism, and excretion studies in drug development: why, when, and how? AB - Absorption, distribution, metabolism, and excretion (ADME) studies are an integral part of the comprehensive safety evaluation of a new molecular entity, and they represent a standard suite of studies included in the registration package for all new small molecule drugs. In vivo studies in preclinical toxicology species and humans using radiolabeled ((3)H or (14)C) compound provide quantitative assessments of overall routes of excretion of drug-related material, pharmacokinetics of total drug-derived radioactivity in circulation, relative to parent compound and quantitation, and characterization of metabolites in excreta and circulation. These data serve as the starting point for metabolite in safety testing (MIST). These studies involve the administration of a radiolabeled drug to laboratory animals and humans followed by a quantitative collection of excreta and blood. Using appropriate plasma-pooling strategies, these studies could allow for modeling the metabolite exposure at the steady state. Information from the radiolabeled human study is used to design clinical drug-drug interaction (DDI) studies and to obtain a waiver for bioequivalence studies. This article describes the various aspects of conducting ADME studies and the use of radiolabeled analogues of drug candidates to investigate their metabolism and how to compare the exposures of metabolites in humans and toxicology species. PMID- 22309196 TI - Identification of an immunomodulating metalloprotease of Pseudomonas aeruginosa (IMPa). AB - Phagocytosis by neutrophils is the essential step in fighting Pseudomonas infections. The first step in neutrophil recruitment to the site infection is the interaction of P-selectin (on endothelial cells) with P-selectin glycoprotein ligand-1 (PSGL-1) on neutrophils. Pseudomonas aeruginosa secretes various proteases that degrade proteins that are essential for host defence, such as elastase and alkaline protease. Here we identify PA0572 of P. aeruginosa as an inhibitor of PSGL-1 and named this secreted hypothetical protease immunomodulating metalloprotease of P. aeruginosa or IMPa. Proteolytic activity was confirmed by cleavage of recombinant and cell-surface expressed PSGL-1. Functional inhibition was demonstrated by impaired PSGL-1-mediated rolling of IMPa-treated neutrophils under flow conditions. Next to PSGL-1, IMPa targets CD43 and CD44 that are also involved in leucocyte homing. These data indicate that IMPa prevents neutrophil extravasation and thereby protects P. aeruginosa from neutrophil attack. PMID- 22309197 TI - Systemic human CR2-targeted complement alternative pathway inhibitor ameliorates mouse laser-induced choroidal neovascularization. AB - PURPOSE: Genetic associations and the presence of complement components within pathological structures of age-related macular degeneration (AMD) have generated the hypothesis that AMD is caused by chronic local complement activation. Since the majority of activity in the common terminal pathway results from engagement of the amplification loop, the alternative pathway has been proposed as a logical therapeutic target. We recently generated a factor H (fH)-based complement inhibitor (CR2-fH) with the capacity to be "targeted" to sites of complement C3 activation. We asked whether the human therapeutic (TT30) is effective in a mouse model of AMD. METHODS: Choroidal neovascularization (CNV) was induced by argon laser photocoagulation of Bruch's membrane. Every other day, mice received intravenous injections of TT30 or vehicles, and after 6 days, the presence or absence of CNV and CNV-related changes were evaluated. Area of CNV, photoreceptor cell function, gene expression for complement components and cytokines, vascular endothelial growth factor (VEGF) protein levels, and TT30 bioavailability were determined. RESULTS: CNV development, which has previously been shown to require local complement activation, could be reduced by intravenous TT30 delivery. Specific inhibition of the alternative pathway not only reduced angiogenesis in CNV, but also ameliorated changes in several associated disease-related biomarkers, including diminished retinal function and molecular events known to be involved in AMD such as VEGF production. After intravenous injection, TT30 localized to CNV lesion sites in the retinal pigmented epithelium-choroid. CONCLUSION: Systemic administration of TT30 was found to reduce CNV pathology. These data may open new avenues for novel systemic AMD treatment strategies. PMID- 22309198 TI - Dermoscopy of small basal cell carcinoma: study of 100 lesions 5 mm or less in diameter. PMID- 22309199 TI - Mitochondrial acetylome analysis in a mouse model of alcohol-induced liver injury utilizing SIRT3 knockout mice. AB - Mitochondrial protein hyperacetylation is a known consequence of sustained ethanol consumption and has been proposed to play a role in the pathogenesis of alcoholic liver disease (ALD). The mechanisms underlying this altered acetylome, however, remain unknown. The mitochondrial deacetylase sirtuin 3 (SIRT3) is reported to be the major regulator of mitochondrial protein deacetylation and remains a central focus for studies on protein acetylation. To investigate the mechanisms underlying ethanol-induced mitochondrial acetylation, we employed a model for ALD in both wild-type (WT) and SIRT3 knockout (KO) mice using a proteomics and bioinformatics approach. Here, WT and SIRT3 KO groups were compared in a mouse model of chronic ethanol consumption, revealing pathways relevant to ALD, including lipid and fatty acid metabolism, antioxidant response, amino acid biosynthesis and the electron-transport chain, each displaying proteins with altered acetylation. Interestingly, protein hyperacetylation resulting from ethanol consumption and SIRT3 ablation suggests ethanol-induced hyperacetylation targets numerous biological processes within the mitochondria, the majority of which are known to be acetylated through SIRT3-dependent mechanisms. These findings reveal overall increases in 91 mitochondrial targets for protein acetylation, identifying numerous critical metabolic and antioxidant pathways associated with ALD, suggesting an important role for mitochondrial protein acetylation in the pathogenesis of ALD. PMID- 22309200 TI - Genetic and biochemical diversity of Gardnerella vaginalis strains isolated from women with bacterial vaginosis. AB - Gardnerella vaginalis is considered a substantial player in the progression of bacterial vaginosis (BV). We analysed 17 G. vaginalis strains isolated from the genital tract of women diagnosed with BV to establish a potential link between genotypes/biotypes and the expression of virulence factors, vaginolysin (VLY) and sialidase, which are assumed to play a substantial role in the pathogenesis of BV. Amplified ribosomal DNA restriction analysis revealed two G. vaginalis genotypes. Gardnerella vaginalis isolates of genotype 2 appeared more complex than genotype 1 and were subdivided into three subtypes. Biochemical typing allowed us to distinguish four different biotypes. A great diversity of the level of VLY production among the isolates of G. vaginalis may be related to a different cytotoxicity level of the strains. We did not find any correlation between VLY production level and G. vaginalis genotype/biotype. In contrast, a link between G. vaginalis genotype and sialidase production was established. Our findings on the diversity of VLY expression level in different clinical isolates and linking sialidase activity with the genotype of G. vaginalis could help to evaluate the pathogenic potential of different G. vaginalis strains. PMID- 22309201 TI - Synthetic studies directed toward dideoxy lomaiviticinone lead to unexpected 1,2 oxazepine and isoxazole formation. AB - In the course of studies directed toward the synthesis of dideoxy lomaiviticinone, 3-(nitromethyl)cyclohexenones 2a (X = H) and 2b (X = I) were prepared. The corresponding enolates were reacted with naphthazarin (1) and unexpectedly afforded 1,2-oxazepine 3 and isoxazole 4, respectively. Rationale for their formation is proposed. PMID- 22309202 TI - Structuring a college alcohol prevention program on the low level of response to alcohol model: a pilot study. AB - BACKGROUND: New approaches are needed to bolster the modest effects of campus drinking prevention programs. However, more definitive research on new paradigms is very expensive, and in the current economic climate, progress can be made by evaluating smaller pilot studies. This study describes one such approach. METHODS: A sample of 18-year-old or older, healthy, drinking freshmen at our university was assigned to 2 groups stratified to be similar on demography, drinking histories, and their level of response (LR) to alcohol. In the spring quarter of the school year, the 32 subjects in each of 2 groups viewed four 45 minute Internet-based videotapes as part of 4 prevention sessions. All 8 modules were based on the same techniques and general content, but the 4 videos for the first group were structured around the validated model of how a low LR affects heavy drinking (the low level of response-based [LRB] Group), with partial mediation by heavier drinking peers, positive alcohol expectancies, and drinking to cope with stress. Videos for the state-of-the-art (SOTA) comparison group did not place the similar prevention messages into the low LR framework. Changes in drinking were evaluated at 3 times: before Module 1, before Module 4, and 1 month after Module 4. RESULTS: Usual and maximum drinks per occasion decreased over time for both high and low LR subjects in both LRB and SOTA groups. As predicted, the low LR students showed greater decreases in the LRB Group, while high LR students showed greater decreases in the more generic SOTA Group. CONCLUSIONS: The results support the hypothesis that tailoring prevention efforts to address specific predisposing factors, such as a low LR, may be associated with beneficial effects on drinking quantity. We hope that these data will encourage additional efforts to validate the low LR-based prevention paradigm and test other interventions that are targeted toward predisposing phenotypes such as impulsivity and negative affect. PMID- 22309204 TI - Soluble CD163 promotes recognition, phagocytosis and killing of Staphylococcus aureus via binding of specific fibronectin peptides. AB - CD163 is a multi-ligand scavenger receptor exclusively expressed by monocytes and macrophages, which is released after their activation during sepsis (sCD163). The biological relevance of sCD163, however, is not yet clear. We now demonstrate that sCD163 exhibits direct antimicrobial effects by recognizing a specific subfragment ((6) F1(1) F2(2) F2(7) F1) of fibronectin (FN) bound to staphylococcal surface molecules. Moreover, contact with staphylococci promotes sCD163-shedding from monocyte surface via induction of metalloproteinases ADAM10 and ADAM17. sCD163 subsequently binds to Staphylococcus aureus via FN peptides and strongly amplifies phagocytosis as well as killing by monocytes and to a lesser extend by neutrophils. This mechanism exhibits additional paracrine effects because staphylococci additionally opsonized by sCD163 induce higher activation and more efficient killing activity of non-professional phagocytes like endothelial cells. Targeting pathogen-bound FN by sCD163 would be a very sophisticated strategy to attack S. aureus as any attempt of the pathogen to avoid this defence mechanism will automatically bring about loss of adherence to the host protein FN, which is a pivotal patho-mechanism of highly invasive staphylococcal strains. Thus, we report a novel function for sCD163 that is of particular importance for immune defence of the host against S. aureus infections. PMID- 22309203 TI - Bone marrow-derived human mesenchymal stem cells express cardiomyogenic proteins but do not exhibit functional cardiomyogenic differentiation potential. AB - Despite their paracrine activites, cardiomyogenic differentiation of bone marrow (BM)-derived mesenchymal stem cells (MSCs) is thought to contribute to cardiac regeneration. To systematically evaluate the role of differentiation in MSC mediated cardiac regeneration, the cardiomyogenic differentiation potential of human MSCs (hMSCs) and murine MSCs (mMSCs) was investigated in vitro and in vivo by inducing cardiomyogenic and noncardiomyogenic differentiation. Untreated hMSCs showed upregulation of cardiac tropopin I, cardiac actin, and myosin light chain mRNA and protein, and treatment of hMSCs with various cardiomyogenic differentiation media led to an enhanced expression of cardiomyogenic genes and proteins; however, no functional cardiomyogenic differentiation of hMSCs was observed. Moreover, co-culturing of hMSCs with cardiomyocytes derived from murine pluripotent cells (mcP19) or with murine fetal cardiomyocytes (mfCMCs) did not result in functional cardiomyogenic differentiation of hMSCs. Despite direct contact to beating mfCMCs, hMSCs could be effectively differentiated into cells of only the adipogenic and osteogenic lineage. After intramyocardial transplantation into a mouse model of myocardial infarction, Sca-1(+) mMSCs migrated to the infarcted area and survived at least 14 days but showed inconsistent evidence of functional cardiomyogenic differentiation. Neither in vitro treatment nor intramyocardial transplantation of MSCs reliably generated MSC-derived cardiomyocytes, indicating that functional cardiomyogenic differentiation of BM-derived MSCs is a rare event and, therefore, may not be the main contributor to cardiac regeneration. PMID- 22309205 TI - Circumstances of death and diagnostic difficulties in brushfire fatalities. AB - The deaths of 10 bushfire (brushfire) victims (aged 2-59 years; M/F 1:1) from the files of Forensic Science SA in Adelaide, South Australia, over an 8-year period (January 2002 to December 2009) are reported. Nine of the victims were found in or near motor vehicles. Death was attributed to incineration (N = 5), trauma from bushfire-related vehicle crashes (N = 2), inhalation of products of combustion with hyperthermia (N = 1), inhalation of products of combustion (N = 1), and undetermined (N = 1). Death scenes covered large areas and involved many victims. Loss of infrastructure and closure of local roads owing to debris limited access and made the finding of bodies difficult. Bodies in such fires may be exposed to the damaging effects of weather and animal predation. Heat damage hindered pathological assessment with resultant delays in identification. Assessment of antemortem injuries and determination of causes of death were also complicated by the condition of some of the bodies. PMID- 22309206 TI - The temporal evolution of electrographic seizure burden in neonatal hypoxic ischemic encephalopathy. AB - PURPOSE: Hypoxic ischemic encephalopathy (HIE) accounts for 60% of all neonatal seizures. There is emerging evidence that seizures cause additional injury to the developing brain that has sustained hypoxic ischemic injury. Temporal evolution of clinical seizure burden in HIE has been characterized, with maximum clinical seizure burden (the period of maximum seizure activity) being observed between 12 and 24 h of age. The purpose of our study was to investigate the distribution of electrographic seizure burden (the accumulated duration of seizures over a defined time period), following the initial hypoxic ischemic insult. METHODS: Fifteen full-term newborns with HIE and seizures, and a minimum of 48 h of continuous video-electroencephalography (EEG), were included in this retrospective study. Medical records of the infants were reviewed and details of clinical seizures and antiepileptic drugs were recorded. The time of maximum seizure burden was defined as the midpoint of an hour-long window, shifted in time by 1 s across the full EEG recording, which contained the maximum duration of seizures. The degree of temporal evolution of seizure burden within this period was tested. Temporal evolution was further analyzed by segmenting the time series into two periods; the time between the first recorded seizure and the maximum seizure burden (T(1)), and the time between the maximum seizure burden and the last recorded seizure (T(2)). Seizure burden, duration, and number of seizures per hour were analyzed within each time period. KEY FINDINGS: EEG was commenced at a median of 14 h of age. Maximum electrographic seizure burden was reached at a median age of 22.7 h. Time from first recorded seizure to maximum seizure burden (T(1)) was significantly shorter than time from maximum seizure burden to last recorded seizure (T(2)) (p-value = 0.01). Median seizure burden during T(1) was significantly higher than during T(2) (p-value = 0.007). There is temporal evolution of electrographic seizure burden in full-term newborns with HIE. There is a short period of high seizure burden (T(1)) followed by a longer period of lower seizure burden (T(2)). SIGNIFICANCE: Understanding the temporal evolution of seizure burden in HIE contributes further to our understanding of neonatal seizures, helps identify an optimal therapeutic window for seizure treatment, and provides a benchmark against which to measure the efficacy of new and innovative forms of neuroprotection and antiepileptic medication. PMID- 22309207 TI - Mitral valve surgery for severe mitral regurgitation and dilated cardiomyopathy- a bridge to transplant: case report and a review of literature. AB - We report a child with myocardial necrosis, dilated cardiomyopathy, and severe mitral valve (MV) regurgitation following neonatal enteroviral myocarditis. He underwent MV annuloplasty at 18 months and MV replacement at 3 years of age. He remains asymptomatic on medical therapy at 8 years of age. Mitral valve surgery may stabilize the evolution of dilated cardiomyopathy and delay the ultimate need for heart transplant. PMID- 22309208 TI - Receptor-ligand interaction-based virtual screening for novel Eg5/kinesin spindle protein inhibitors. AB - Eg5/KSP is a promising mitotic spindle target for drug discovery in cancer chemotherapy and the development of agents against fungal diseases. A range of Eg5 targeting compounds identified by in vitro or cell-based screening is currently in development. We employed structure-based virtual screening of a database of 700, 000 compounds to identify three novel Eg5 inhibitors bearing quinazoline (24) or thioxoimidazolidine (30 and 37) scaffolds. The new compounds inhibit Eg5 ATPase activity, show growth inhibition in proliferation assays, and induce monoastral spindles in cells, the characteristic phenotype for Eg5 inhibiting agents. This is the first successful reported procedure for the identification of Eg5 inhibitors via receptor-ligand interaction-based virtual screening. PMID- 22309209 TI - Perinatal depression screening and intervention: enhancing health provider involvement. AB - OBJECTIVE: The authors of this study collaborated in the analysis of public health survey data in order to inform future statewide interventions that could systematically enhance depression screening and mental health service use for women of reproductive age. The primary objective of the study was to empirically inform and test the program theory components of a motivational interviewing intervention that we anticipate will guide statewide practice and policy priorities. METHODS: Data were examined from a survey of healthcare practitioners statewide (n=1498) regarding their practices with and perceptions of perinatal depression care for women. Confirmatory factor analysis (CFA) was used to measure two latent constructs: health provider confidence in the ability to diagnose and treat and the importance placed on screening and treatment. Structural equation modeling (SEM) was used to test a program theory supporting motivational interviewing using a model implied relationship between confidence and importance on screening and treatment/referral practices. RESULTS: The data fit the model; the model provisionally supports motivational interviewing as an intervention influencing provider attitudes and practices surrounding perinatal depression screening and treatment/referral. CONCLUSIONS: Ultimately, study findings support statewide public health efforts to expand the role of health providers in recognizing and responding to perinatal depression and suggest that motivational interviewing techniques that augment importance and confidence may lead to enhanced screening and referral/treatment outcomes for pregnant and postpartum women. PMID- 22309210 TI - Human papillomavirus vaccination practices among providers in Indian health service, tribal and urban Indian healthcare facilities. AB - PURPOSE: The human papillomavirus (HPV) vaccine is of particular importance in American Indian/Alaska Native women because of the higher rate of cervical cancer incidence compared to non-Hispanic white women. To better understand HPV vaccine knowledge, attitudes, and practices among providers working with American Indian/Alaska Native populations, we conducted a provider survey in Indian Health Service, Tribal and Urban Indian (I/T/U) facilities. METHODS: During December 2009 and January 2010, we distributed an on-line survey to providers working in I/T/U facilities. We also conducted semistructured interviews with a subset of providers. RESULTS: There were 268 surveys and 51 provider interviews completed. Providers were more likely to administer vaccine to 13-18-year-olds (96%) than to other recommended age groups (89% to 11-12-year-olds and 64% to 19-26-year-olds). Perceived barriers to HPV vaccination for 9-18-year-olds included parental safety and moral/religious concerns. Funding was the main barrier for 19-26-year-olds. Overall, providers were very knowledgeable about HPV, although nearly half of all providers and most obstetricians/gynecologists thought that a pregnancy test should precede vaccination. Sixty-four percent of providers of patients receiving the vaccine do not routinely discuss the importance of cervical cancer screening. CONCLUSIONS: Recommendations for HPV vaccination have been broadly implemented in I/T/U settings. Vaccination barriers identified by I/T/U providers are similar to those reported in other provider surveys. Provider education efforts should stress that pregnancy testing is not needed before vaccination and the importance of communicating the need for continued cervical cancer screening. PMID- 22309211 TI - Retention of dental sealants placed on sound teeth and incipient caries lesions as part of a service-learning programme in rural areas in Mexico. AB - BACKGROUND: Dental sealants are an effective treatment for the prevention and management of caries. OBJECTIVE: To determine the retention of sealants placed in a rural setting in Mexico as part of an international service-learning (ISL) programme and to determine associations between dental sealant's retention and caries diagnosis at the time of sealant placement. METHODS: Children aged 6-15 were examined for dental caries, received sealants by dental students as part of an ISL programme, and were re-examined 4, 2, or 1 years after placement to assess sealant survival. Sealants were placed on permanent sound surfaces and enamel caries lesions [International Caries Assessment and Detection System (ICDAS) criteria]. Sealant survival was explored using Cochran-Mantel-Haenszel tests and multivariate prediction models. RESULTS: 219 (46%) of 478 (mean age = 10.53 SD = 5.11) children who had received sealants returned for a recall examination (mean age = 10.89 SD = 3.11). After 1-4 years, 96.4% to 60.6% of the sealants placed on sound teeth had survived, and for sealants placed on surfaces with enamel caries lesions (ICDAS 1-3), 94.2% to 55.6% had survived. Differences were not statistically significant. CONCLUSIONS: Sealants had survival rates comparable to those previously reported in the literature. Sealants placed on sound and enamel caries lesions had similar survival rates. PMID- 22309212 TI - Novel missense mutation in the IGF-I receptor L2 domain results in intrauterine and postnatal growth retardation. AB - BACKGROUND: IGFs play key roles in intrauterine and postnatal growth through the IGF-I receptor (IGF-IR). We identified a family bearing a new heterozygous missense mutation at the L2 domain of IGF-IR (R431L). METHOD: We analysed the nucleotide sequences of the IGF1R gene of the family. We prepared R(-) cells (fibroblasts with targeted disruption of the IGF-IR gene) expressing wild-type or R431L IGF-IR and performed functional analyses by evaluating IGF-I binding, IGF-I stimulated DNA synthesis, tyrosine phosphorylation of IGF-IR and its substrates, and internalization by measuring [(125) I]IGF-I internalization. We also performed confocal microscopy analysis. RESULTS: We identified a family bearing a new heterozygous missense mutation at the L2 domain of IGF-IR (R431L) through an 8-year-old girl and her mother, both born with intrauterine growth retardation. In experiments conducted using cells homozygously transfected with the IGF-IR R431L mutation; (i) IGF-I binding was not affected; (ii) DNA synthesis induced by IGF-I was decreased; (iii) IGF-IR internalization stimulated by IGF-I was decreased and (iv) IGF-I-stimulated tyrosine phosphorylation was reduced IGF-IR by low concentrations of IGF-I and on insulin receptor substrate (IRS)-1 and IRS 2. CONCLUSION: A missense mutation (R431L) leads to the inhibition of cell proliferation, attenuation of IGF signalling and decrease in internalization of IGF-IR. The results of this study suggest a novel link between a mutation at the IGF-IR L2 domain and intrauterine and postnatal growth retardation. PMID- 22309213 TI - Identification of a molecular component of the mitochondrial acetyltransferase programme: a novel role for GCN5L1. AB - SIRT3 (sirtuin 3) modulates respiration via the deacetylation of lysine residues in electron transport chain proteins. Whether mitochondrial protein acetylation is controlled by a counter-regulatory program has remained elusive. In the present study we identify an essential component of this previously undefined mitochondrial acetyltransferase system. We show that GCN5L1 [GCN5 (general control of amino acid synthesis 5)-like 1; also known as Bloc1s1] counters the acetylation and respiratory effects of SIRT3. GCN5L1 is mitochondrial-enriched and displays significant homology with a prokaryotic acetyltransferase. Genetic knockdown of GCN5L1 blunts mitochondrial protein acetylation, and its reconstitution in intact mitochondria restores protein acetylation. GCN5L1 interacts with and promotes acetylation of SIRT3 respiratory chain targets and reverses global SIRT3 effects on mitochondrial protein acetylation, respiration and bioenergetics. The results of the present study identify GCN5L1 as a critical prokaryote-derived component of the mitochondrial acetyltransferase programme. PMID- 22309214 TI - Enantioselective construction of pyrrolidines by palladium-catalyzed asymmetric [3 + 2] cycloaddition of trimethylenemethane with imines. AB - A protocol for the enantioselective [3 + 2] cycloaddition of trimethylenemethane (TMM) with imines has been developed. Central to this effort were the novel phosphoramidite ligands developed in our laboratories. The conditions developed to effect an asymmetric TMM reaction using 2-trimethylsilylmethyl allyl acetate were shown to be tolerant of a wide variety of imine acceptors to provide the corresponding pyrrolidine cycloadducts with excellent yields and selectivities. Use of a bis-2-naphthyl phosphoramidite allowed the successful cycloaddition of the parent TMM with N-Boc imines, and has further permitted the reaction of substituted donors with N-tosyl aldimines and ketimines in high regio-, diastereo , and enantioselectivity. Use of a diphenylazetidine ligand allows the complementary synthesis of the exocyclic nitrile product shown, and we demonstrate control of the regioselectivity of the product based on manipulation of the reaction parameters. PMID- 22309215 TI - A novel training model for Mohs surgeons. PMID- 22309216 TI - Lectin chromatography/mass spectrometry discovery workflow identifies putative biomarkers of aggressive breast cancers. AB - We used a lectin chromatography/MS-based approach to screen conditioned medium from a panel of luminal (less aggressive) and triple negative (more aggressive) breast cancer cell lines (n=5/subtype). The samples were fractionated using the lectins Aleuria aurantia (AAL) and Sambucus nigra agglutinin (SNA), which recognize fucose and sialic acid, respectively. The bound fractions were enzymatically N-deglycosylated and analyzed by LC-MS/MS. In total, we identified 533 glycoproteins, ~90% of which were components of the cell surface or extracellular matrix. We observed 1011 glycosites, 100 of which were solely detected in >=3 triple negative lines. Statistical analyses suggested that a number of these glycosites were triple negative-specific and thus potential biomarkers for this tumor subtype. An analysis of RNaseq data revealed that approximately half of the mRNAs encoding the protein scaffolds that carried potential biomarker glycosites were up-regulated in triple negative vs luminal cell lines, and that a number of genes encoding fucosyl- or sialyltransferases were differentially expressed between the two subtypes, suggesting that alterations in glycosylation may also drive candidate identification. Notably, the glycoproteins from which these putative biomarker candidates were derived are involved in cancer-related processes. Thus, they may represent novel therapeutic targets for this aggressive tumor subtype. PMID- 22309219 TI - Disruption of the fusion of Leishmania parasitophorous vacuoles with ER vesicles results in the control of the infection. AB - Parasitophorous vacuoles (PV) that harbour Leishmania parasites acquire some characteristics from fusion with host cell vesicles. Recent studies have shown that PVs acquire and display resident endoplasmic reticulum (ER) molecules. We investigated the importance of ER molecules to PV biology by assessing the consequence of blocking the fusion of PVs with vesicles that originate from the early secretory pathway. This was achieved by targeting the N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs) that mediate the fusion of early secretory vesicles. In the presence of dominant negative variants of sec22b or some of its known cognate partners, D12 and syntaxin 18, PVs failed to distend and harboured fewer parasites. These observations were confirmed in studies in which each of the SNAREs listed above including the intermediate compartment ER/Golgi SNARE, syntaxin 5, was knocked down. The knock-down of these SNARES had little or no measurable effect on the morphology of the ER or on activated secretion even though they resulted in a more significant reduction of PV size. Moreover, the knock-down of the ER/Golgi SNAREs resulted in significant reduction in parasite replication. Taken together, these studies provide further evidence that PVs acquire ER components by fusing with vesicles derived from the early secretory pathway; disruption of this interaction results in inhibition of the development of PVs as well as the limitation of parasite replication within infected cells. PMID- 22309217 TI - Correlates of recovery from alcohol dependence: a prospective study over a 3-year follow-up interval. AB - BACKGROUND: Correlates of recovery from alcohol dependence have been identified through a variety of study designs characterized by different strengths and limitations. The goal of this study was to compare correlates of recovery based on a 3-year prospective design with those based on cross-sectional analyses of data from the same source. METHODS: Data from the 2001 to 2002 Wave 1 and 2004 to 2005 Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were used to examine baseline characteristics associated with Wave 2 recovery from alcohol dependence, among those who classified with past-year DSM IV alcohol dependence at Wave 1 (n = 1,172). RESULTS: Abstinent recovery was significantly associated with Black/Asian/Hispanic race/ethnicity, children <1 year of age in the household at baseline, attending religious services greater than or equal to weekly at follow-up, and having initiated help-seeking that comprised/included 12-step participation within <3 years prior to baseline. Nonabstinent recovery was positively associated with being never married at baseline, having job problems or being unemployed in the year preceding baseline, attending religious services less than weekly at follow-up, baseline smoking and volume of ethanol intake, and having terminated a first marriage within <3 years prior to baseline. Findings, including others of marginal significance (0.05 < p < 0.10), generally supported results from prior pseudo-prospective survival analyses with time-dependent covariates but differed in many ways from cross sectional analyses of Wave 1 NESARC data. CONCLUSIONS: Various aspects of study design must be considered when interpreting correlates of recovery. Cross sectional analyses of lifetime correlates of recovery are highly subject to misinterpretation, but pseudo-prospective survival analyses with time-dependent covariates may yield results as valid as those from prospective studies. PMID- 22309220 TI - Mutations of the SCN1A gene in acute encephalopathy. AB - PURPOSE: Acute encephalopathy is the most serious complication of pediatric viral infections, such as influenza and exanthema subitum. It occurs worldwide, but is most prevalent in East Asia. Recently, there have been sporadic case reports of epilepsy/febrile seizure and acute encephalopathy with a neuronal sodium channel alpha 1 subunit (SCN1A) mutation. To determine whether SCN1A mutations are a predisposing factor of acute encephalopathy, we sought to identify SCN1A mutations in a large case series of acute encephalopathy including various syndromes. METHODS: We analyzed the SCN1A gene in 87 patients with acute encephalopathy, consisting of 20 with acute necrotizing encephalopathy (ANE), 61 with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), and six with nonspecific (unclassified) acute encephalopathy. KEY FINDINGS: Three patients had distinct point mutations. Two of them had epileptic seizures prior to acute encephalopathy. Clinical and neuroradiologic findings of acute encephalopathy were diverse among the three patients, although all had a prolonged and generalized seizure at its onset. The first patient with V982L had partial epilepsy and AESD. The second patient with M1977L had febrile seizures and nonspecific acute encephalopathy. The third patient with R1575C had no seizures until the onset of ANE. M1977L was a novel mutation, whereas the remaining two, V982L and R1575C, have previously been reported in cases of Dravet syndrome and acute encephalopathy, respectively. SIGNIFICANCE: These findings provide further evidence that SCN1A mutations are a predisposing factor for the onset of various types of acute encephalopathy. PMID- 22309221 TI - Determination of an effective housekeeping gene for the quantification of mRNA for forensic applications. AB - The potential application of mRNA for the identification of biological fluids using molecular techniques has been a recent development in forensic serology. Constitutively expressed housekeeping genes can assess the amount of mRNA recovered from a sample, establish its suitability for downstream applications, and provide a reference point to corroborate the identity of the fluid. qPCR was utilized to compare the expression levels of housekeeping genes from forensic like body fluid stains to establish the most appropriate assessment of human mRNA quantity prior to profiling. Although variability was observed between fluids and individuals, results indicated that beta-2 microglobulin exhibited the highest expression for all body fluids examined and across donors. A one-way analysis of variance was performed for housekeeping gene variability between donors (at the alpha, 0.05, significance level), and the results indicated significant differences for semen, vaginal secretions, and menstrual blood. PMID- 22309222 TI - Benign mediastinal lymphadenopathy presenting as cor triatriatum. AB - This report describes a patient with a superior mediastinal mass and extensive intrathoracic lymphadenopathy referred for oncologic care. During her evaluation, an abnormal cardiovascular examination resulted in an echocardiographic evaluation and an unanticipated diagnosis of a highly obstructive left atrial cor triatriatum was uncovered. The patient underwent repair of cor triatriatum and lymph node biopsy shortly after the diagnosis was made. The biopsies revealed reactive lymph nodes with lymphatic dilation and no inflammatory or neoplastic features. To our knowledge, this case represents the first pediatric example of extensive mediastinal lymphadenopathy mimicking the appearance of a malignant process as a result of severe pulmonary venous hypertension. PMID- 22309223 TI - Melanin-concentrating hormone receptor 1 antagonists. Synthesis and structure activity relationships of novel 3-(aminomethyl)quinolines. AB - It was found that 3-(aminomethyl)quinoline derivatives showed high binding affinities for melanin-concentrating hormone receptor 1 (MCHR1) with reduced affinity for serotonin receptor 2c (5-HT2c) when the dihydronaphthalene nucleus of compound 1 (human MCHR1, IC(50) = 1.9 nM; human 5-HT2c receptor, IC(50) = 0.53 nM) was replaced by other bicyclic core scaffolds. Among the synthesized compounds, 8-methylquinoline derivative 5v especially showed high binding affinity (IC(50) = 0.54 nM), potent in vitro antagonistic activity (IC(50) = 2.8 nM) for MCHR1, and negligible affinity for 5-HT2c receptor (IC(50) > 1000 nM). Oral administration of 5v significantly and dose-dependently suppressed nocturnal food intake in diet-induced obese rats and did not affect food intake in MCHR1 deficient mice. These results and rat pharmacokinetic study findings suggested that compound 5v is a highly potent, orally bioavailable, and centrally acting nonpeptide MCHR1 antagonist. PMID- 22309224 TI - Spinocerebellar ataxia type 1 (SCA1): new pathoanatomical and clinico pathological insights. AB - AIMS: Spinocerebellar ataxia type 1 (SCA1) represents the first molecular genetically characterized autosomal dominantly inherited cerebellar ataxia and is assigned to the CAG-repeat or polyglutamine diseases. Owing to limited knowledge about SCA1 neuropathology, appropriate pathoanatomical correlates of a large variety of SCA1 disease symptoms are missing and the neuropathological basis for further morphological and experimental SCA1 studies is still fragmentary. METHODS: In the present study, we investigated for the first time serial tissue sections through the complete brains of clinically diagnosed and genetically confirmed SCA1 patients. RESULTS: Brain damage in the three SCA1 patients studied went beyond the well-known brain predilection sites of the underlying pathological process. Along with neuronal loss in the primary motor cortex, it included widespread degeneration of gray components of the basal forebrain, thalamus, brainstem and cerebellum, as well as of white matter components in the cerebellum and brainstem. It involved the motor cerebellothalamocortical and basal ganglia-thalamocortical circuits, the visual, auditory, somatosensory, oculomotor, vestibular, ingestion-related, precerebellar, basal forebrain cholinergic and midbrain dopaminergic systems. CONCLUSIONS: These findings show for the first time that the extent and severity of brain damage in SCA1 is very similar to that of clinically closely related spinocerebellar ataxias (that is, SCA2, SCA3 and SCA7). They offer suitable explanations for poorly understood SCA1 disease symptoms and will facilitate the interpretation of further morphological and experimental SCA1 studies. PMID- 22309225 TI - Replacement of mouse embryonic fibroblasts with bone marrow stromal cells for use in establishing and maintaining embryonic stem cells in mice. AB - We have investigated the use of BMSC (bone marrow stromal cell) as a feeder cell for improving culture efficiency of ESC (embryonic stem cell). B6CBAF1 blastocysts or ESC stored after their establishment were seeded on to a feeder layer of either SCA-1+/CD45-/CD11b- BMSC or MEF (mouse embryonic fibroblast). Feeder cell activity in promoting ESC establishment from the blastocysts and in supporting ESC maintenance did not differ significantly between BMSC and MEF feeders. However, the highest efficiency of colony formation after culturing of inner cell mass cells of blastocysts was observed with the BMSC line that secreted the largest amount of LIF (leukaemia inhibitory factor). Exogenous LIF was essential for the ESC establishment on BMSC feeder, but not for ESC maintenance. Neither change in stem cell-specific gene expression nor increase in stem cell aneuploidy was detected after the use of BMSC feeder. We conclude that BMSC can be utilized as the feeder of ESC, which improves culture efficiency. PMID- 22309226 TI - Salivary levels of Bifidobacteria in caries-free and caries-active children. AB - BACKGROUND: Salivary levels of Bifidobacteria have been shown to be significantly correlated with caries experience in adults but not as yet in children. HYPOTHESIS: Salivary levels of Bifidobacteria are positively associated with caries experience in children. AIM: To compare the salivary concentrations of Bifidobacteria of caries-free and caries-active children. DESIGN: Saliva was collected using the tongue-loop method from 38 caries-active children and from 22 clinically caries-free children, and the numbers of Bifidobacteria, mutans streptococci, lactobacilli and yeasts were determined. Additionally, the age and gender of the children, a plaque index, sugar amount in diet, sugar frequency in diet, hygiene practice and fluoride toothpaste usage were recorded. RESULTS: Bifidobacteria were isolated from 95% of the caries-active children and from only 9% of the caries-free children (P < 0.001). Salivary levels of Bifidobacteria were significantly correlated with amount of sugar in the diet, frequency of sugar consumption and oral hygiene practice. The significant variables that discriminated between the caries-free and caries-active subjects were salivary levels of Bifidobacteria, salivary levels of mutans streptococci and oral hygiene practice (chi(2) = 72.57, P < 0.001) and overall 90.0% of cases were correctly classified. CONCLUSIONS: Salivary levels of Bifidobacteria are significantly associated with caries experience in children. The salivary levels of this genus may be a useful marker of caries risk. PMID- 22309227 TI - Hydrogen bond strength modulates the mechanical strength of ferric-thiolate bonds in rubredoxin. AB - It has long been recognized that hydrogen bonds formed by protein backbone amides with cysteinyl S(gamma) atoms play important roles in modulating the functional and structural properties of the iron-sulfur centers in proteins. Here we use single molecule atomic force microscopy, cyclic voltammetry, and protein engineering techniques to investigate directly how the strength of N-H...S(gamma) hydrogen bonds in the secondary coordination sphere affects the mechanical stability of Fe(III)-thiolate bonds of rubredoxin. Our results show that the mechanical stability of Fe(III)-thiolate bonds in rubredoxin correlates with the strength of N-H...S(gamma) hydrogen bonds as reflected by the midpoint reduction potential, providing direct evidence that N-H...S(gamma) hydrogen bonds play important roles in modulating the mechanical and kinetic properties of the Fe(III)-thiolate bonds of iron-sulfur proteins and corroborating the important roles of the protein environment in tuning the properties of metal-thiolate bonds. PMID- 22309228 TI - Salvaging kidneys with renal allograft compartment syndrome. AB - Renal allograft compartment syndrome is an under recognized cause of early allograft dysfunction which can be reversed by early intervention. It occurs early after renal transplantation where closure of the anterior abdominal wall seems to compress the transplant in the limited retroperitoneal space. The literature about this syndrome in renal transplantation is sparse. Our report describes the diagnostic criteria and the management of two renal transplant recipients with this syndrome. Its diagnosis depends upon duplex vascular scan findings of reversed or absent diastolic flow in the renal vasculature in the absence of any perigraft collection or severe acute tubular necrosis. In our hands emergency laparotomy, decompression of the transplant and closure with interposition mesh salvaged these kidneys. PMID- 22309229 TI - The nasofacial sulcus as a primary donor site for full-thickness skin grafts of the nasal alar and distal nose. PMID- 22309230 TI - Proteome mapping of human skim milk proteins in term and preterm milk. AB - The abundant proteins in human milk have been well characterized and are known to provide nutritional, protective, and developmental advantages to both term and preterm infants. However, relatively little is known about the expression of the low abundance proteins that are present in human milk because of the technical difficulties associated with their detection. We used a combination of electrophoretic techniques, ProteoMiner treatment, and two-dimensional liquid chromatography to examine the proteome of human skim milk expressed between 7 and 28 days postpartum by healthy term mothers and identified 415 in a pooled milk sample. Of these, 261 were found in human skim milk for the first time, greatly expanding our understanding of the human skim milk proteome. The majority of the proteins identified were involved in either the immune response (24%) or in cellular (28%) or protein (16%) metabolism. We also used iTRAQ analysis to examine the effects of premature delivery on milk protein composition. Differences in protein expression between pooled milk from mothers delivering at term (38-41 weeks gestation) and preterm (28-32 weeks gestation) were investigated, with 55 proteins found to be differentially expressed with at least 90% confidence. Twenty-eight proteins were present at higher levels in preterm milk, and 27 were present at higher levels in term milk. PMID- 22309231 TI - Resistin in gingival crevicular fluid and induction of resistin release by Porphyromonas gingivalis lipopolysaccharide in human neutrophils. AB - BACKGROUND AND OBJECTIVE: Resistin is an adipocytokine that induces insulin resistance and is predominantly expressed in adipocytes and peripheral blood mononuclear cells. Resistin expression increases in inflammatory diseases as well as diabetes mellitus, and is upregulated by bacterial pathogens and proinflammatory cytokines. The aim of this study was to identify resistin in human gingival crevicular fluid, to compare the resistin levels in gingival crevicular fluid between subjects with and without periodontitis and diabetes mellitus and to investigate the regulation of resistin release from human neutrophils by Porphyromonas gingivalis lipopolysaccharide (P-LPS). MATERIAL AND METHODS: Gingival crevicular fluid samples were collected from patients with chronic periodontitis (n = 24), patients with diabetes mellitus-related periodontitis (n = 18) and healthy subjects (n = 21). Resistin in gingival crevicular fluid was determined using western blot analysis and an ELISA kit. The glycated hemoglobin (HbA(1c)) value was obtained from patients with diabetes mellitus-related periodontitis by a medical interview. Human neutrophils were cultured with P-LPS (0-1000 ng/mL), or incubated with inhibitors of actin or microtubule polymerization in the absence or presence of P-LPS. The medium and cellular fractions were used for determination of resistin by ELISA. RESULTS: The resistin level in gingival crevicular fluid from patients with periodontitis or diabetes mellitus-related periodontitis was significantly higher than that of healthy subjects. The resistin level in gingival crevicular fluid was correlated with gingival index score, but not blood HbA(1c) value. The P-LPS increased resistin release from human neutrophils, and its induction was decreased by actin polymerization inhibitors. CONCLUSION: We show, for the first time, the presence of resistin in gingival crevicular fluid. A high resistin level in gingival crevicular fluid samples from periodontitis patients may to some extent be related to P-LPS-induced resistin release from neutrophils. PMID- 22309233 TI - Development of a microRNA delivery system based on bacteriophage MS2 virus-like particles. AB - Recently, microRNA (miRNA)-mediated RNA interference has been developed as a useful tool in gene function analysis and gene therapy. A major obstacle in miRNA mediated RNAi is cellular delivery, which requires an efficient and flexible delivery system. The self-assembly of the MS2 bacteriophage capsids has been used to develop virus-like particles (VLPs) for RNA and drug delivery. However, MS2 VLP-mediated miRNA delivery has not yet been reported. We therefore used an Escherichia coli expression system to produce the pre-miR 146a contained MS2 VLPs, and then conjugated these particles with HIV-1 Tat(47-57) peptide. The conjugated MS2 VLPs effectively transferred the packaged pre-miR146a RNA into various cells and tissues, with 0.92-14.76-fold higher expression of miR-146a in vitro and about two-fold higher expression in vivo, and subsequently suppressed its targeting gene. These findings suggest that MS2 VLPs can be used as a novel vehicle in miRNA delivery systems, and may have applications in gene therapy. PMID- 22309232 TI - Defects in autophagy favour adherent-invasive Escherichia coli persistence within macrophages leading to increased pro-inflammatory response. AB - Ileal lesions in Crohn's disease (CD) patients are abnormally colonized by pathogenic adherent-invasive Escherichia coli (AIEC). AIEC bacteria are able to replicate within epithelial cells after lysis of the endocytic vacuole and within macrophages in a large vacuole. CD-associated polymorphisms in NOD2, ATG16L1 and IRGM affect bacterial autophagy, a crucial innate immunity mechanism. We previously determined that defects in autophagy impaired the ability of epithelial cells to control AIEC replication. AIEC behave differently within epithelial cells and macrophages and so we investigated the impact of defects in autophagy on AIEC intramacrophagic replication and pro-inflammatory cytokine response. AIEC bacteria induced the recruitment of the autophagy machinery at the site of phagocytosis, and functional autophagy limited AIEC intramacrophagic replication. Impaired ATG16L1, IRGM or NOD2 expression induced increased intramacrophagic AIEC and increased secretion of IL-6 and TNF-alpha in response to AIEC infection. In contrast, forced induction of autophagy decreased the numbers of intramacrophagic AIEC and pro-inflammatory cytokine release, even in a NOD2-deficient context. On the basis of our findings, we speculate that stimulating autophagy in CD patients would be a powerful therapeutic strategy to concomitantly restrain intracellular AIEC replication and slow down the inflammatory response. PMID- 22309234 TI - Borderline personality symptoms in short-term and long-term abstinent alcohol dependence. AB - BACKGROUND: Comorbidity of borderline personality disorder (BPD) and substance and alcohol use disorders (SUDs and AUDs) is very high. The literature suggests a negative synergy between BPD and SUDs, which may impact an individual's ability to achieve and maintain remission of either disorder in the face of the other. METHODS: We examined lifetime and current (past year) BPD symptom counts in 3 gender- and age-comparable groups: short-term abstinent alcoholics (STA, 6 to 15 weeks abstinent), long-term abstinent alcoholics (LTA, more than 18 months abstinent), and nonsubstance-abusing controls (NSAC). Abstinent individuals were recruited primarily from mutual-help recovery networks and about half had comorbid drug dependence. BPD symptoms were obtained using the Structured Clinical Interview for DSM-IV-TR Axis II Personality Disorders, followed up with questions regarding currency, but did not require that BPD symptoms represent persistent or pervasive behavior such as would meet criteria for BPD diagnosis. Thus, our study dealt only with BPD symptoms, not BPD diagnoses. RESULTS: Alcoholics had more lifetime and current symptoms for most all BPD criteria than NSAC. In general, STA and LTA did not differ in BPD symptoms, except for a group by-gender effect for both lifetime and current anger-associated symptoms and for lifetime abandonment avoidance symptoms. For these cases, there were much higher symptom counts for STA women versus men, with comparable symptom counts for LTA women versus men. CONCLUSIONS: Our results suggest for the most part that BPD symptoms do not prevent the maintenance of recovery in AUD and SUD individuals who have established at least 6 weeks abstinence within the mutual-help recovery network-in fact the presence of BPD symptoms is the norm. However, we did find difficulty in establishing longer-term abstinence in women with anger-associated symptoms and abandonment avoidance symptoms. PMID- 22309235 TI - Rescue therapy for acute migraine, part 2: neuroleptics, antihistamines, and others. AB - OBJECTIVES: This second portion of a 3-part series examines the relative effectiveness of headache treatment with neuroleptics, antihistamines, serotonin antagonists, valproate, and other drugs (octreotide, lidocaine, nitrous oxide, propofol, and bupivacaine) in the setting of an emergency department, urgent care center, or headache clinic. METHODS: MEDLINE was searched using the terms "migraine" AND "emergency" AND "therapy" OR "treatment." Reports were from emergency department and urgent care settings and involved all routes of medication delivery. Reports from headache clinics were only included if medications were delivered by a parenteral route. RESULTS: Prochlorperazine, promethazine, and metoclopramide, when used alone, were superior to placebo. Droperidol and prochlorperazine were superior or equal in efficacy to all other treatments, although they also have more side effects (especially akathisia). Metoclopramide was equivalent to prochlorperazine and, when combined with diphenhydramine, was superior in efficacy to triptans and non-steroidal anti inflammatory drugs. Meperidine was inferior to chlorpromazine and equivalent to the other neuroleptics. The overall percentage of patients with pain relief after taking droperidol and prochlorperazine was equivalent to sumatriptan. CONCLUSIONS: Prochlorperazine and metoclopramide are the most frequently studied of the anti-migraine medications in the emergent setting, and the effectiveness of each is superior to placebo. Prochlorperazine is superior or equivalent to all other classes of medications in producing migraine pain relief. Dopamine antagonists, in general, appear to be equivalent for migraine pain relief to the migraine-"specific" medications sumatriptan and dihydroergotamine, although there are fewer studies involving the last two. Lack of comparisons to placebo and the frequent use of combination medications in treatment arms complicate the comparison of single agents to one other. PMID- 22309236 TI - Additive perturbed molecular assembly in two-dimensional crystals: differentiating kinetic and thermodynamic pathways. AB - During attempts to produce novel two-dimensional cocrystals by coadsorbing components in a binary mixture, the formation of a metastable form was observed in analogy to the phenomenon of additive-induced polymorph formation reported in three-dimensional crystallization. Mechanistic insights into this phenomenon were gained through the use of scanning tunneling microscopy and several adsorbate/additive combinations. One additive plays a critical role in forming a disordered assembly through a process that is primarily kinetic whereas another additive thermodynamically stabilized an intermediate form, resulting in interrupting a phase transformation to a more stable form. These additive effects elucidate one of the potential pathways to kinetically isolate a metastable polymorph formed during cocrystallization in three-dimensional crystallization. PMID- 22309237 TI - Toward the selective delivery of chemotherapeutics into tumor cells by targeting peptide transporters: tailored gold-based anticancer peptidomimetics. AB - Complexes [Au(III)X(2)(dtc-Sar-AA-O(t-Bu))] (AA = Gly, X = Br (1)/Cl (2); AA = Aib, X = Br (3)/Cl (4); AA = l-Phe, X = Br (5)/Cl (6)) were designed on purpose in order to obtain gold(III)-based anticancer peptidomimetics that might specifically target two peptide transporters (namely, PEPT1 and PEPT2) upregulated in several tumor cells. All the compounds were characterized by means of FT-IR and mono- and multidimensional NMR spectroscopy, and the crystal structure of [Au(III)Br(2)(dtc-Sar-Aib-O(t-Bu))] (3) was solved and refined. According to in vitro cytotoxicity studies, the Aib-containing complexes 3 and 4 turned out to be the most effective toward all the human tumor cell lines evaluated (PC3, DU145, 2008, C13, and L540), reporting IC(50) values much lower than that of cisplatin. Remarkably, they showed no cross-resistance with cisplatin itself and were proved to inhibit tumor cell proliferation by inducing either apoptosis or late apoptosis/necrosis depending on the cell lines. Biological results are here reported and discussed in terms of the structure activity relationship. PMID- 22309239 TI - Detection of Avian bornavirus 5 RNA in Eclectus roratus with feather picking disorder. AB - Avian bornavirus (ABV) was discovered recently in parrots with proventricular dilatation disease (PDD), a fatal neurological disease. Although ABV has been shown to be a causative agent of PDD, its virological characteristics are largely unknown. Here we report the detection of ABV genotype 5 RNA in an Eclectus roratus with feather picking disorder (FPD). Interestingly, although the bird was persistently infected with ABV5 for at least 8 months, it had no clinical signs of PDD. Although it remains unclear whether ABV5 is associated with FPD, these findings raise the importance of epidemiological studies of birds with diseases other than PDD. PMID- 22309238 TI - Intravenous alteplase in ischemic stroke patients not fully adhering to the current drug license in Central and Eastern Europe. AB - BACKGROUND: The current European license for alteplase in acute ischemic stroke excludes from treatment large groups of patients. Nevertheless, in everyday practice, many patients receive off-label thrombolysis at the physician's discretion. AIM: Our aim was to evaluate safety and effectiveness of intravenous alteplase in patients not fully adhering to the drug license compared with those treated strictly according to the license in Central and Eastern Europe. METHODS: We analyzed the data contributed to Safe Implementation of Thrombolysis in Stroke registry from nine countries between February 2003 and February 2010. Statistical analysis included multivariate logistic regression. RESULTS: Of 5594 consecutive patients, 1919 patients (34.3%) not fully adhered to the license. The most frequent deviations were: time-to-treatment >3 h (13.1%), use of intravenous antihypertensives (8.3%), age >80 years (7.3%), oral anticoagulation (4.2%), a previous stroke with concomitant diabetes (3.9%), and previous stroke 3 h was an independent predictor of unfavorable outcome (odds ratio 1.32; 95% confidence interval: 1.01-1.71). CONCLUSION: Our findings show that patients not fully adhering to the European license are not at increased risk of symptomatic intracranial haemorrhage but achieve less favorable outcome. Some contraindications appear more redundant than others. However, the final conclusions about safety and effectiveness should be based on the results of ongoing randomized trials. PMID- 22309240 TI - First report of subcutaneous phaeohyphomycosis caused by Ochroconis tshawytschae in an immunocompetent patient. AB - We report the first case and clinical course of a case of human subcutaneous phaeohyphomycosis caused by Ochroconis tshawytschae, a rare fish pathogen. The diagnosis was based upon histopathological and mycological examinations of clinical samples. Identification of the etiologic agent was assessed on its phenotypic characteristics and subsequently, confirmed by molecular data. In vitro antifungal susceptibility of the isolate was investigated and a comparison was prepared of all of its features to those of its two most relevant related species, O. gallopava and O. humicola. PMID- 22309241 TI - Epidemiology of pemphigus in the western region of Turkey: retrospective analysis of 87 patients. AB - BACKGROUND: Pemphigus is a worldwide disease and varies in its clinical profile and epidemiology in different regions of the world. The disease is rare and few epidemiological data are available. OBJECTIVE: The purpose of this study was to evaluate the epidemiologic, clinical, and therapeutic features of pemphigus in the western region of Turkey. METHODS: We retrospectively investigated a total of 87 patients with pemphigus. The parameters including age at diagnosis, sex, diagnostic delay, diagnostic methods, hospitalizations, distribution of skin lesions, duration and dose of therapy, side effects, and duration of follow-up were evaluated. RESULTS: The mean age at the onset was 48 years. The average annual incidence of the disease was seven new patients and estimated annual incidence rate was 0.18 per 100,000 inhabitants. The male-to-female ratio was 1/1.64. All patients were treated with systemic corticosteroids. The mean initial dose was 100 mg prednisolone equivalent. Thirty-three (37.9%) patients received azathioprine as adjuvant therapy. The mean time to control the disease activity was 23 days in our study group. Ten patients (11.5%) were in clinical remission without treatment, 41 patients (47.1%) were on low dose steroid (<= 10 mg daily), and 28 (32.2%) were using > 10 mg/day corticosteroid at the end of the study period. CONCLUSION: Pemphigus vulgaris (PV) is the most common clinical subtype in the western part of Turkey. The disease is more frequent in the fifth decade of life and has a female predominance in our region. The patients with both oral mucosa and skin involvement need higher corticosteroid dose, more time to control the disease activity and longer hospitalization time when compared with the patients with oral mucosa involvement alone. PMID- 22309242 TI - Restoration of adipose function in obese glucose-tolerant men following pioglitazone treatment is associated with CCAAT enhancer-binding protein beta up regulation. AB - Obese AT (adipose tissue) exhibits increased macrophage number. Pro-inflammatory CD16+ peripheral monocyte numbers are also reported to increase with obesity. The present study was undertaken to simultaneously investigate obesity-associated changes in CD16+ monocytes and ATMs (AT macrophages). In addition, a pilot randomized placebo controlled trial using the PPAR (peroxisome-proliferator activated receptor) agonists, pioglitazone and fenofibrate was performed to determine their effects on CD14+/CD16+ monocytes, ATM and cardiometabolic and adipose dysfunction indices. Obese glucose-tolerant men (n=28) were randomized to placebo, pioglitazone (30 mg/day) and fenofibrate (160 mg/day) for 12 weeks. A blood sample was taken to assess levels of serum inflammatory markers and circulating CD14+/CD16+ monocyte levels via flow cytometry. A subcutaneous AT biopsy was performed to determine adipocyte cell surface and ATM number, the latter was determined via assessment of CD68 expression by IHC (immunohistochemistry) and real-time PCR. Subcutaneous AT mRNA expression of CEBPbeta (CCAAT enhancer-binding protein beta), SREBP1c (sterol-regulatory element-binding protein 1c), PPARgamma2, IRS-1 (insulin receptor substrate-1), GLUT4 (glucose transporter type 4) and TNFalpha (tumour necrosis factor alpha) were also assessed. Comparisons were made between obese and lean controls (n=16) at baseline, and pre- and post-PPAR agonist treatment. Obese individuals had significantly increased adipocyte cell surface, percentage CD14+/CD16+ monocyte numbers and ATM number (all P=0.0001). Additionally, serum TNF-alpha levels were significantly elevated (P=0.017) and adiponectin levels reduced (total: P=0.0001; high: P=0.022) with obesity. ATM number and percentage of CD14+/CD16+ monocytes correlated significantly (P=0.05). Pioglitazone improved adiponectin levels significantly (P=0.0001), and resulted in the further significant enlargement of adipocytes (P=0.05), without effect on the percentage CD14+/CD16+ or ATM number. Pioglitazone treatment also significantly increased subcutaneous AT expression of CEBPbeta mRNA. The finding that improvements in obesity-associated insulin resistance following pioglitazone were associated with increased adipocyte cell surface and systemic adiponectin levels, supports the centrality of AT to the cardiometabolic derangement underlying the development of T2D (Type 2 diabetes) and CVD (cardiovascular disease). PMID- 22309243 TI - Pulpotomy in caries-exposed immature permanent molars using calcium-enriched mixture cement or mineral trioxide aggregate: a randomized clinical trial. AB - OBJECTIVE: To compare clinical and radiographic outcomes of pulpotomy treatment using calcium-enriched mixture (CEM) cement and mineral trioxide aggregate (MTA) in carious-exposed vital immature permanent first molars. DESIGN: Fifty-one immature molars with clinical carious exposure with symptomatic/asymptomatic pulpitis met the inclusion criteria and randomly assigned to one of the treatment groups (CEM [26 teeth; 59 roots], MTA [25 teeth; 59 roots]). After performing pulpotomy and covering the radicular pulps with the biomaterials, all teeth were permanently restored. Blinded clinical and radiographic evaluations were performed at 6 and 12 months after operation for signs of success or failure. Radiographs were evaluated for complete/partial apical closure. The data were analysed using chi-square test and generalized estimating equation (GEE) model. RESULTS: There was no significant difference at the baseline between the two experimental groups. All available cases (49 teeth) showed pulp survival and signs of continuous root development after 12 months. Overall, complete apical closure (apexogenesis) occurred in 76.8% and 73.8% of radiographically interpreted roots in CEM cement and MTA groups, respectively. There was no statistical difference in terms of radiographic outcomes between two groups. CONCLUSIONS: Calcium-enriched mixture cement and MTA showed similar performance in pulpotomy of immature caries-exposed permanent molars. PMID- 22309244 TI - Effects of folic acid on the development and oxidative stress of mouse embryos exposed to heat stress. AB - The development of mammalian pre-implantation embryos is inhibited by heat stress, and the inhibitory effect is associated with excess reactive oxygen species (ROS). Folate is a nutrient with various physiological functions including antioxidative effects. We first investigated the transcript expression for 10 enzymes in the cycle of folate metabolism (folate-methionine cycle) in mouse embryos at the 1-cell, 2-cell, 4- to 8-cell, morula and blastocyst stages using reverse transcription-polymerase chain reaction. All of the transcripts were consistently expressed, except for Mat1a, which was not detected from the 4- to 8-cell stage onward. Next, the effects of folic acid (the synthetic form of folate) on the development and ROS levels of heat-stressed embryos were investigated. One-cell mouse embryos were cultured with or without 1000 ng/ml folic acid basically at 38 degrees C, and in the heat-stressed groups, embryos were exposed to 39.5 degrees C/10 h/day on the first two days of culture. The heat stress significantly (p < 0.05) decreased blastocyst development and cell number and increased ROS levels compared to those in the group not subjected to heat stress; however, among the heat-stressed groups, blastocyst development and cell number were increased and the ROS level was decreased by the addition of folic acid. These results indicate that the mRNA of folate-methionine cycle enzymes are expressed in mouse pre-implantation embryos, suggesting they can independently utilize folate, and the inhibitory effects of heat stress on the development of mouse pre-implantation embryos are ameliorated by folic acid. The ameliorating effects of folic acid may be partly due to its antioxidative property. PMID- 22309245 TI - Three-dimensional organization of block copolymers on "DNA-minimal" scaffolds. AB - Here, we introduce a 3D-DNA construction method that assembles a minimum number of DNA strands in quantitative yield, to give a scaffold with a large number of single-stranded arms. This DNA frame is used as a core structure to organize other functional materials in 3D as the shell. We use the ring-opening metathesis polymerization (ROMP) to generate block copolymers that are covalently attached to DNA strands. Site-specific hybridization of these DNA-polymer chains on the single-stranded arms of the 3D-DNA scaffold gives efficient access to DNA-block copolymer cages. These biohybrid cages possess polymer chains that are programmably positioned in three dimensions on a DNA core and display increased nuclease resistance as compared to unfunctionalized DNA cages. PMID- 22309246 TI - Herbal bioactive molecules: the hidden jewels for drug development. Introduction. PMID- 22309248 TI - Implementation and usefulness of single-access laparoscopic segmental and total colectomy. AB - AIM: Single-access laparoscopic surgery is a recent vogue in the field of minimally invasive colorectal surgery. While selected series have indicated feasibility, we prospectively examined its usefulness for resectional surgery in routine practice. METHOD: All patients undergoing laparoscopic colorectal resection over a 12-month period were considered for a single-access approach by a single surgical team in a university hospital. This utilized a 'glove' port via a 3-5 cm periumbilical or stomal site incision, with standard rigid laparoscopic instruments then being used. RESULTS: Of 76 planned laparoscopic colorectal resections, 35 (47%) were performed by this single-incision laparoscopic modality without disruption of theatre list efficiency or surgical training obligations. The mean (range) age and body mass index of these 25 consecutive right-sided resections, eight total colectomies (seven urgent operations) and two anterior resections was 58 (22-82) years and 23.9 (18.6-36.2) kg/m(2) , respectively. The modal postoperative day of discharge was 4. For right-sided resections, the mean (range) postoperative stay in those undergoing surgery for benign disease was 4.0 days, while for those undergoing operation for neoplasia (n=18, mean age 71 years) it was 5.8 days and the average lymph node harvest was 13. Use of the glove port reduced trocar cost by 58% (?60/L53) by allowing the use of trocar sleeves alone without obturators. CONCLUSION: Single-incision laparoscopic surgery is an effective option for abdominal surgery and seems especially suited for laparoscopic-assisted right-sided colonic resections. The glove port technique facilitates procedural frequency and familiarity and proves economically favourable. PMID- 22309247 TI - Health-care transition from pediatric to adult-focused gastroenterology in patients with eosinophilic esophagitis. PMID- 22309249 TI - Social environment affects juvenile dispersal in great tits (Parus major). AB - 1. Habitat selection can affect individual fitness, and therefore, individuals are expected to assess habitat quality of potential breeding sites before settlement. 2. We investigated the role of social environment on juvenile dispersal behaviour in the great tit (Parus major). Two main contradictory hypotheses can be formulated regarding social effects on juvenile dispersal as follows: (i) High fledgling density and sex ratio may enhance the intensity of local (kin) competition and, therefore, reduce individual survival chance, enhance emigration and reduce settlement ('repulsion' hypothesis) (ii) Alternatively, high fledgling density and sex ratio may signal high-quality habitat or lead to aggregation and thus increase individual survival chance, reduce emigration and enhance settlement ('attraction' hypothesis). 3. To disentangle positive from negative effects of high density and male-biased sex ratio on dispersal, we manipulated the social composition of the fledgling population in 12 semi-isolated nest-box areas (plots) via a change of fledgling density (low/high) as well as fledgling sex ratio (female-biased/balanced/male biased) across 3 years. We then tested whether experimental variation in male and female fledgling densities affected variation in local survival, emigration and settlement of juveniles, and whether social effects on survival and dispersal support the 'repulsion' or 'attraction' hypothesis. 4. We found no experimental effects on local survival and emigration probabilities. However, consistent with the 'attraction' hypothesis, settlement was significantly and positively affected by local experimental sex ratio in each of the study years: both male and female juveniles avoided female-biased plots and settled more in plots that were balanced and male-biased the previous year. 5. Our study provides unprecedented experimental evidence that local sex ratio plays a causal role in habitat selection. We suggest that settlers avoid female-biased plots because a high proportion of females may reflect the absence or the low quality of local resources in the habitat. Alternatively, male territory acquisition may be facilitated by a high local density of 'candidate' males, and therefore, juveniles were less successful in settling in female-biased plots. PMID- 22309250 TI - STAT-3 inhibitory bisabolanes from Carthamus glaucus. AB - Apart from a large amount (ca. 2.0%) of alpha-bisabolol beta-D-fucopyranoside (2a), the aerial parts of the Mediterranean weed Carthamus glaucus afforded an unusual triglyceride (E-2-crotonyl-1,3-distearolylglycerol, 7), two lipophilic flavonoids (6a,b), and a series of bisabolane fucopyranosides variously acylated on the sugar moiety (2b-e) or oxidized on the terpenoid core (3, 4a,b, 5a,b). The fucopyranoside 2a is more soluble in polar media and more versatile in terms of formulation than its aglycone [(-)-alpha-bisabolol, 1], an anti-inflammatory cosmetic ingredient in current short supply in its natural form. A comparative investigation of the activity of alpha-bisabolol (1a), the fucopyranoside 2a, and its senecioate 2b on transcription factors involved in inflammation and cancer pathways (NF-kappaB and STAT-3) showed only marginal activity on NF-kappaB inhibition for all compounds, while STAT-3 was inhibited potently by the fucoside 2a and, to a lesser extent, also by alpha-bisabolol. These observations qualify 2a as an easily available compound, both as an apoptotic lead structure and as a potential alternative to natural alpha-bisabolol (1) for pharmaceutical and/or cosmetic development. PMID- 22309251 TI - Arrhythmogenic difference between the left and right atria in a canine ventricular pacing-induced heart failure model of atrial fibrillation. AB - BACKGROUND: The detail of biatrial activation during sustained atrial fibrillation (AF) has not been investigated until now. METHODS: Five dogs with right ventricular pacing-induced congestive heart failure (CHF) and five normal dogs were included. Biatrial endocardiac mapping was performed using noncontact mapping system. RESULTS: Noncontact mapping of the right atrium (RA) showed CHF dogs had a higher frequency of focal discharge from Bachmann's bundle, sinoatrial region, and crista terminalis. CHF dogs also had a higher frequency of wave break, wave fusion, and reentry. CHF dogs had greater effective refractory period (ERP) dispersion. Noncontact mapping of the left atrium (LA) showed CHF dogs had more frequent focal discharge from left superior pulmonary vein (PV), right superior PV, and left atrial appendage. CHF dogs had a higher frequency of wave break, wave fusion, and reentry. CHF dogs had greater ERP dispersion. Comparison between RA and LA showed LA had a higher frequency of focal discharge, wave break, wave fusion, and leading circle reentry than the RA. LA also had greater ERP dispersion than RA. CONCLUSION: CHF dogs had a higher frequency of focal discharge and reentry, suggesting that CHF provided an arrhythmogenic substrate. LA had a higher frequency of focal discharge and reentry, suggesting that LA is more important to maintain AF. PMID- 22309252 TI - The contribution of Barrie Edwards to the treatment of colic in the horse: an international perspective. PMID- 22309253 TI - Current understanding of PTX3 protective activity on Aspergillus fumigatus infection. AB - Infection caused by Aspergillus fumigatus remains a major therapeutic challenge in immunocompromised individuals. Innate immunity represents the first line of defense against pathogens. In the last 20 years, several proteins belonging to this arm of the immune system have been characterized as being endowed with antifungal activity. Among these, the prototype long pentraxin PTX3 has been identified as a non-redundant protective factor against infections caused by A. fumigatus. A number of relevant animal models of invasive aspergillosis have indicated that PTX3 exerts its protective activity in several conditions of immunosuppression. In this article, we review the current understanding of PTX3 mechanisms of action that might be of help in further exploration of the pharmacological activity of this protein against A. fumigatus. PMID- 22309254 TI - Lack of association between air pollutant exposure and short-term risk of ischaemic stroke in Lyon, France. AB - BACKGROUND: Some observational and experimental studies have suggested a short term relationship between air pollutants and ischaemic stroke; however, the results conflict. AIMS: The objective of this study was to investigate the association between particulate matter less than 2.5 and 10 microns in aerodynamic diameter, nitrogen dioxide, sulphur dioxide and ozone, and short-term risk of ischaemic stroke in Lyon, France. METHODS: The AVC69 study was a multicenter cohort study in which all consecutive adult patients admitted to one of the emergency or neurological departments of the Rhone area for suspicion of stroke were included during a seven-month period. Only patients with ischaemic stroke living within the study area, composed of Lyon and 18 neighbouring communities with homogenous air pollutants exposure, formed the basis of our study. We adopted a time-stratified case-crossover design to analyse the short term effect (up to two-days) of air pollutants on ischaemic stroke incidence. Models were adjusted for temperature, variation of atmospheric pressure, minimal relative humidity, influenza epidemics, pollen count, and holidays. Stratified analyses by gender and class age were performed. Different lag times were analysed. RESULTS: 376 patients were included. Mean age was 76.6 years (+/- 13.7). 53.7% were women. No association was observed between air pollutants and short-term risk of ischaemic stroke after adjustment for main confounding factors. Results remained unchanged whatever the gender or age. CONCLUSIONS: These results suggest a lack of association between air pollutant exposure and short-term risk of ischaemic stroke in a French urban area. PMID- 22309255 TI - Crystal structure of a ring-cleaving cyclohexane-1,2-dione hydrolase, a novel member of the thiamine diphosphate enzyme family. AB - The thiamine diphosphate (ThDP) dependent flavoenzyme cyclohexane-1,2-dione hydrolase (CDH) (EC 3.7.1.11) catalyses a key step of a novel anaerobic degradation pathway for alicyclic alcohols by converting cyclohexane-1,2-dione (CDO) to 6-oxohexanoate and further to adipate using NAD(+) as electron acceptor. To gain insights into the molecular basis of these reactions CDH from denitrifying anaerobe Azoarcus sp. strain 22Lin was structurally characterized at 1.26 A resolution. Notably, the active site funnel is rearranged in an unprecedented manner providing the structural basis for the specific binding and cleavage of an alicyclic compound. Crucial features include a decreased and displaced funnel entrance, a semi-circularly shaped loop segment preceding the C terminal arm and the attachment of the C-terminal arm to other subunits of the CDH tetramer. Its structural scaffold and the ThDP activation is related to that observed for other members of the ThDP enzyme family. The selective binding of the competitive inhibitor 2-methyl-2,4-pentane-diol (MPD) to the open funnel of CDH reveals an asymmetry of the two active sites found also in the dimer of several other ThDP dependent enzymes. The substrate binding site is characterized by polar and non-polar moieties reflected in the structures of MPD and CDO and by three prominent histidine residues (His28, His31 and His76) that most probably play a crucial role in substrate activation. The NAD(+) dependent oxidation of 6 oxohexanoate remains enigmatic as the redox-active cofactor FAD seems not to participate in catalysis, and no obvious NAD(+) binding site is found. Based on the structural data both reactions are discussed. PMID- 22309256 TI - Targeting HLA class I expression to increase tumor immunogenicity. AB - The dynamic interaction between the host immune system and growing cancer has been of central interest to the field of tumor immunology over the past years. Recognition of tumor-associated antigens (TAA) by self-HLA (human leukocyte antigen) class I-restricted CD8+ T cells is a main feature in the detection and destruction of malignant cells. The discovery and molecular characterization of TAA has changed the field of cancer treatment and introduced a new era of cancer immunotherapy aimed at increasing tumor immunogenicity and T-cell-mediated anti tumor immunity. Unfortunately, while these new protocols of cancer immunotherapy are mediating induction of tumor-specific T lymphocytes in patients with certain malignancies, they have not yet delivered substantial clinical benefits, such as induction of tumor regression or increased disease-free survival. It has become apparent that lack of tumor rejection is the result of immune selection and escape by tumor cells that develop low immunogenic phenotypes. Substantial experimental data support the existence of a variety of different mechanisms involved in the tumor escape phase, including loss or downregulation of HLA class I antigens. These alterations could be caused by regulatory ('soft') or by structural/irreversible ('hard') defects. On the basis of the evidence obtained from experimental mouse cancer models and metastatic human tumors, the structural defects underlying HLA class I loss may have profound implications on T-cell mediated tumor rejection and ultimately on the outcome of cancer immunotherapy. Strategies to overcome this obstacle, including gene therapy to recover normal expression of HLA class I genes, require consideration. In this review, we outline the importance of monitoring and correction of HLA class I alterations during cancer development and immunotherapy. PMID- 22309257 TI - Analysis of HLA-DM polymorphisms in the Chinese Han population. AB - Non-classical human leukocyte antigen (HLA)-DM plays an important and unique role in the processing and presentation of exogenous antigens. Polymorphisms of certain genes and frequency of alleles in populations may indicate susceptibility to certain diseases. In this study, the analysis of HLA-DMA and HLA-DMB gene polymorphisms and haplotypes in the Chinese Han population was conducted to obtain population genetic data. HLA-DM typing has been performed previously by other groups by polymerase chain reaction (PCR)-restriction fragment length polymorphism and PCR-sequence-specific oligonucleotide probe techniques. In this study, we established a TaqMan PCR typing method as an alternative to these techniques to survey the frequency of DMA and DMB alleles in the population. Genotyping was conducted in 1000 unrelated individuals of Han nationality in South and North China using TaqMan PCR typing. Four different DMA alleles and six different DMB alleles were detected. All loci met the Hardy-Weinberg equilibrium principle that both allele and genotype frequencies in a population remain constant. We found that the DMA*01:01 (69.35%) and DMB*01:01 (52.5%) alleles were more frequent in Chinese Hans. Analysis of the haplotypes for two loci of DMA and DMB showed that a highly significant positive linkage disequilibrium (LD) presented for DMA*01:01-DMB*01:02, DMA*01:01-DMB*01:03, DMA*01:01-DMB*01:04, DMA*01:02-DMB*01:01, DMA*01:02-DMB*01:05, DMA*01:03-DMB*01:07, and DMA*01:04 DMB*01:01 haplotypes. Analysis of haplotypes for four loci associated with antigen processing (DMA-DMB-TAP1-TAP2) showed a highly significant LD in DMA*01:01-DMB*01:04-TAP1*02:01:01-TAP2*01:02, DMA*01: 02-DMB*01:05-TAP1*01:01 TAP2*01:01, and DMA*01:01-DMB*01:03-TAP1* 04:01-TAP2*01:01 haplotypes. The comparison between the Chinese Han population and non-Chinese populations showed that no significant differences were found at the HLA-DMA locus in the Chinese Han population compared with people of German nationality, whereas significant differences presented when compared with Turkish, American Caucasian, Japanese, French, and Italian nationalities. However, at the HLA-DMB locus, highly significant differences presented in the Chinese Han population compared with Germans and Italians. This study lays the foundations for further disease association analyses. PMID- 22309258 TI - Sequence evolution and escape from specific immune pressure of an HIV-1 Rev epitope with extensive sequence similarity to human nucleolar protein 6. AB - Antigen-specific immunity is crucially important for containing viral replication in human immunodeficiency virus (HIV)-1-infected hosts. Several epitopes have been predicted for the early expressed HIV-1 proteins Tat and Rev, but few have been studied in detail. We characterized the human leukocyte antigen (HLA)-B44 restricted Rev epitope EELLKTVRL (EL9) in an HIV-1-infected subject treated with antiretroviral therapy. Interestingly, a high sequence similarity was found between the EL9 epitope and the human nucleolar protein 6 (NOL6). However, this similarity does not seem to impede immunogenicity as CD8(+) T-cells, previously stimulated with EL9-pulsed dendritic cells, were able to specifically recognize the HIV-1 Rev epitope without cross-recognizing the human self-antigen NOL6. After the subject interrupted antiretroviral therapy and virus rebounded, mutations within the EL9 epitope were identified. Although the emerging mutations resulted in decreased or abolished T-cell recognition, they did not impair Rev protein function. Mutations leading to escape from T-cell recognition persisted for up to 124 weeks following treatment interruption. This study shows that the HLA-B44-restricted Rev CD8(+) T-cell epitope EL9 is immunogenic notwithstanding its close resemblance to a human peptide. The epitope mutates as a consequence of dynamic interaction between T-cells and HIV-1. Clinical status, CD4(+) T-cell count and viral load remained stable despite escape from T-cell recognition. PMID- 22309259 TI - Nomenclature for factors of the HLA system, update October 2011. PMID- 22309260 TI - Nomenclature for factors of the HLA system, update November 2011. PMID- 22309261 TI - Nomenclature for factors of the HLA system, update December 2011. PMID- 22309262 TI - Retraction. A gene-specific primer extension and liquid bead array system for killer cell immunoglobulin-like receptor genotyping. PMID- 22309263 TI - Understanding the molecular pharmacology of the serotonergic system: using fluoxetine as a model. AB - OBJECTIVES: Serotonin is a monoamine neurotransmitter that is widely distributed in the body and plays an important role in a variety of psychological and other body functions such as mood, sexual desire and function, appetite, sleep, memory and learning, temperature regulation and social behaviour. This review will assess the use of fluoxetine, one of the most commonly used selective serotonin reuptake inhibitors, as a model for understanding the molecular pharmacology of the serotoninergic system. KEY FINDINGS: Seven serotonin receptor families have been discovered to date. All serotonin receptors, except 5-HT(3), are G-protein coupled, seven transmembrane receptors that activate an intracellular second messenger cascade. The 5-HT(3) receptor is a ligand-gated ion channel. Furthermore, 5-HT(1A) receptors are known as autoreceptors since their stimulation inhibits the release serotonin in nerve terminals. A transporter protein found in the plasma membrane of serotonergic neurones is responsible for the reuptake of this neurotransmitter. Selective serotonin reuptake inhibitors, such as fluoxetine, act primarily at the serotonin transporter protein and have limited, if any, reaction with other neurotransmitter systems. Selective serotonin reuptake inhibitors appear to bind with the serotonin transporter with different rates of occupancy, duration and potency. SUMMARY: The following review focuses on the interaction of serotonin with this membrane transporter in the body and assesses the use of fluoxetine as a reference drug in the understanding of this interaction. PMID- 22309264 TI - Everted gut sac model as a tool in pharmaceutical research: limitations and applications. AB - OBJECTIVES: This review discusses the limitations and applications of the everted gut sac model in studying drug absorption, metabolism, and interaction. KEY FINDINGS: The mechanism of drug absorption, interaction and the effect of factors such as age, sex, species, chronic therapy, and disease state on drug absorption have been summarized. The experimental conditions and their effects on the outcomes of trials have been discussed also. SUMMARY: The everted sac model is an efficient tool for studying in-vitro drug absorption mechanisms, intestinal metabolism of drugs, role of transporter in drug absorption, and for investigating the role of intestinal enzymes during drug transport through the intestine. PMID- 22309265 TI - Single-dose pharmacokinetics and safety of iptakalim hydrochloride in Chinese healthy volunteers. AB - OBJECTIVES: To investigate the safety, pharmacokinetics and food effect of iptakalim in healthy adult Han Chinese volunteers. METHODS: Study 1 was a randomized open-label, Latin square designed, single-dose, three-period, self control crossover study. Six men and six women received 5, 10 and 20 mg of iptakalim orally. Study 2 was a randomized, open-label, single-dose, two-period, self-control crossover study. Ten men were included and each subject received 5 mg iptakalim orally, fasting and nonfasting. KEY FINDINGS: No adverse effects were reported and no clinically meaningful changes in vital signs were found. Cmax, AUC(0-t) and AUC(0-infinity) were proportional over the dose levels of 5, 10 and 20 mg. Tmax, t1/2 and CL/F were similarly independent of dose level. In the 5 mg and 20 mg group, the Cmax, AUC(0-t) and AUC(0-infinity) in women were significantly higher than in men, although they showed no difference after correction by mg/kg doses in the 5 mg group. At the 5-mg dose level, no significant difference in pharmacokinetics was found in nonfasting and fasting subjects. CONCLUSIONS: Single-dose pharmacokinetics of iptakalim showed dose proportionality over the dose levels of 5-20 mg. The pharmacokinetics showed gender differences in the 5 and 20 mg groups. Food had almost no impact on the pharmacokinetics at the 5 mg level. PMID- 22309266 TI - Effect of low-protein diet on anthracycline pharmacokinetics and cardiotoxicity. AB - OBJECTIVES: Anthracyclines are broad spectrum anticancer drugs with dose dependent cardiotoxicity. Protein malnutrition commonly occurs in cancer patients and is considered a risk factor for development of cardiotoxicity. This study was designed to assess the modulatory effect of protein malnutrition on the pharmacokinetics and drug disposition properties of a single dose of doxorubicin and epirubicin and how these possible changes will affect the degree of cardiotoxicity of these drugs. METHODS: A single interperitoneal dose of 15 mg/kg of either doxorubicin or epirubicin was injected into rats fed with either normal protein diet or low-protein diet. The plasma concentration-time profiles of doxorubicin and epirubicin and their concentrations in different tissues were determined. Serum creatine kinase level was determined at different time intervals and histopathological examination of heart tissue was carried out. KEY FINDINGS: Protein malnutrition significantly altered the pharmacokinetics of doxorubicin and epirubicin, with a significant decrease in their elimination, and prolonged the exposure of the heart to these drugs. Histopathological examination and serum creatine kinase measurements supported the role of protein malnutrition in enhancement of anthracycline cardiotoxicity. CONCLUSIONS: If similar alteration in anthracyclines' pharmacokinetics occurs in malnourished cancer patients, protein malnutrition will be a risk factor for development of anthracycline cardiotoxicity and dose adjustment will be required in nutritionally deprived patients. PMID- 22309267 TI - Single injection of ONO-1301-loaded PLGA microspheres directly after ischaemia reduces ischaemic damage in rats subjected to middle cerebral artery occlusion. AB - OBJECTIVES: ONO-1301 was developed as a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. In this study, we investigated the therapeutic time window of oral ONO-1301 and the effect of a single subcutaneous injection of ONO-1301-loaded poly(lactide-co-glycolide) (PLGA) microspheres (ONO 1301 PLGA MS) on infarction volume, functional deficits and plasma ONO-1301 levels following a 1 h middle cerebral artery occlusion (MCAO) in rats. METHODS: Rats were treated with ONO-1301 (3 mg/kg) orally twice-daily starting 1 (directly), 6 or 24 h after MCAO. Rats received a single subcutaneous injection of ONO-1301 PLGA MS (10 mg/kg) directly after MCAO. Neurological scores were evaluated directly after, 1 and 6 h, 1, 2, and 3 days after MCAO. Infarct volume, oedema and plasma ONO-1301 levels were measured three days after MCAO. KEY FINDINGS: Neurological scores, oedema and infarct volume were all significantly improved in rats repeatedly treated with oral ONO-1301 and subcutaneous ONO-1301 PLGA MS directly after MCAO. Plasma ONO-1301 levels were significantly lower in rats treated directly after MCAO (either with ONO-1301 or ONO-1301 PLGA MS) than in rats treated 6 h or 24 h after MCAO. CONCLUSIONS: ONO-1301 PLGA MS subcutaneous treatment directly after MCAO showed a neuroprotective effect as well as oral ONO-1301. This treatment should be clinically more convenient than ONO-1301 oral administration since it is delivered as a single treatment after MCAO. PMID- 22309268 TI - Quantitative crystallinity determination for E1010, a novel carbapenem antibiotic, using differential scanning calorimetry. AB - OBJECTIVES: The objective of this study was to develop a quantitative crystallinity analysis method for the bulk drug of E1010 ((+)-(4R,5S,6S)-6-[(R)-1 hydroxyethyl]-3-[(2S,4S)-2-[(R)-1-hydroxy-1-[(R)-pyrrolidin-3 yl]methyl]pyrrolidin-4-yl]thio-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2 carboxylic acid monohydrochloride), a novel carbapenem antibiotic. METHODS: X-ray analyses, thermal analyses and hygroscopicity measurements were used to elucidate the crystal structure and the solid state properties. To develop a quantitative method for the crystallinity of E1010 bulk drug, the relationship between enthalpy change obtained by differential scanning calorimetry (DSC) and crystalline form ratio was investigated. KEY FINDINGS: E1010 bulk drug was found to exist in a crystalline trihydrate formed in two layers, i.e. a layer of E1010 free form, and a layer consisting of chloride ions and water molecules. The thermal analysis showed an endothermic peak derived from dehydration with the loss of crystal lattices at around 100 degrees C as an onset. The enthalpy change value for the endothermic peak correlated well with crystalline content in binary physical mixtures of the crystalline trihydrate and the amorphous form. In addition, for nine lots of the bulk drug, a positive correlation between the enthalpy change and chemical stability in the solid state was observed. CONCLUSIONS: This quantitative analysis of crystallinity using DSC could be applicable for the quality control of the bulk drug to detect variability among manufacturing batches and to estimate the chemical stability of partially amorphous samples. PMID- 22309269 TI - Liposomal topotecan formulation with a low polyethylene glycol grafting density: pharmacokinetics and antitumour activity. AB - OBJECTIVES: PEGylated liposomes could evade recognition by the reticulo endothelial system and prolong the circulation time of vesicles, resulting in enhanced targeting efficiency and antitumour effect. Typically, vesicles are modified with distearoylphosphatidylethanolamine (DSPE)-polyethylene glycol (PEG) at a high PEG grafting density. However, long circulation time and slow drug release rate might induce severe hand-foot syndrome in clinical practice. In this study, a liposomal topotecan formulation with a low PEG grafting density was prepared and its pharmacokinetics, acute toxicity and antitumour effect were investigated. METHODS: Topotecan was loaded into liposomes using an ammonium sulfate gradient. The resulting formulation was injected to healthy Wistar rats at different dose levels to investigate whether its clearance followed linear kinetics. Biodistribution was performed in Lewis lung cancer-bearing mice. The acute toxicity was evaluated in healthy mice and beagle dogs. To compare the antitumour effects of different formulations and dose schedule, RM-1 prostate, Lewis lung, H446 and L1210 cancer models were used. KEY FINDINGS: Topotecan could be encapsulated into low DSPE-PEG liposomes with ~100% loading efficiency. The clearance of the liposomal formulation followed linear kinetics at a dose level ranging from 0.5 to 4 mg/kg despite the fact that the vesicles were coated at a low PEG density. Compared with free topotecan the liposomal formulation preferentially accumulated into tumour zones instead of normal tissues. Both formulations could rapidly accumulate into liver and tumour, but the liposomal formulation was cleared from tissues at a slow rate relative to the conventional formulation. In rats and beagle dogs, liposomal formulations could not induce skin toxicity. In all the tumour models, smaller split doses were more therapeutically active than larger doses when the overall dose intensity was equivalent. CONCLUSIONS: This has been the first report that plasma kinetics of a liposomal formulation with a low PEG density followed linear kinetics. Moreover, due to its short circulation half-life, the formulation did not induce skin toxicity. Our data revealed that the dose schedule of liposomal drugs should be adjusted in accordance with the biophysical and biological properties of the formulations to achieve the optimal therapeutic efficacy. PMID- 22309270 TI - Comparison of in-vivo and in-silico methods used for prediction of tissue: plasma partition coefficients in rat. AB - OBJECTIVES: To use methods from the literature to predict rat tissue:plasma partition coefficients (Kps) and volume of distribution values. Determine which model provides the most accurate predictions to increase confidence in the use of predicted pharmacokinetic parameters in physiologically based pharmacokinetic modelling. METHODS: Six models were used to predict Kps and four to predict V(ss) for a dataset of 81 compounds in 11 rat tissues, and the predictions were compared with experimentally derived values. KEY FINDINGS: Kp predictions made by the Rodgers et al. model were the most accurate, with 77% within threefold of experimental values. The Poulin & Theil model was the most accurate for the prediction of V(ss) , with 87% of predictions within threefold. CONCLUSIONS: This study has shown that in-silico models available in the literature can be used to accurately predict Kp and V(ss) in rat. The Rodgers et al. model has been shown to provide the most accurate Kp predictions, with consistent accuracy across all drug classes and tissues. It was also the most accurate V(ss) predictor when no in-vivo data were used as input. However, transporter systems and other mechanisms that are not yet fully understood need to be incorporated into these types of models in the future to further increase their applicability. PMID- 22309271 TI - Pharmacokinetic study of liposome-encapsulated and plain mepivacaine formulations injected intra-orally in volunteers. AB - OBJECTIVES: The pharmacokinetics of commercial and liposome-encapsulated mepivacaine (MVC) injected intra-orally in healthy volunteers was studied. METHODS: In this double blind, randomized cross-over study, 15 volunteers received, at four different sessions, 1.8 ml of the following formulations: 2% MVC with 1 : 100 000 epinephrine (MVC(2%EPI) ), 3% MVC (MVC(3%) ), 2% and 3% liposome-encapsulated MVC (MVC(2%LUV) and MVC(3%LUV) ). Blood samples were collected pre dose (0 min) and at 15, 30, 45, 60, 90, 120, 180, 240, 300, 360 min after injections. Liquid chromatography-tandem mass spectrometry was used to quantify plasma MVC concentrations. RESULTS: Pharmacokinetic analysis showed that the maximum plasma concentration (Cmax) and the areas under the curves (AUC(0 360) and AUC(0-infinity)) after MVC(2%LUV) and MVC(2%EPI) injections were smaller (P < 0.05) than the equivalent figures for MVC(3%) and MVC(3%LUV). The time to maximum plasma concentration (Tmax) and the half-life of elimination (t1/2beta) obtained after the treatment with MVC(2%LUV), MVC(2%EPI), MVC(3%) and MVC(3%LUV) presented no statistically significant differences (P > 0.05). Cmax, AUC(0-360) and AUC(0-infinity) after injection of the 2% formulations (MVC(2%LUV) and MVC(2%EPI) ) did not exhibit statistically significant differences (P > 0.05). The pharmacokinetics of MVC(2%LUV) were comparable to the pharmacokinetics of MVC(2%EPI). CONCLUSION: The liposomal formulation of 2% MVC exhibits similar systemic absorption to the local anesthetic with vasoconstrictor. PMID- 22309272 TI - Effects of diarylpentanoid analogues of curcumin on chemiluminescence and chemotactic activities of phagocytes. AB - OBJECTIVES: A series of 43 curcumin diarylpentanoid analogues were synthesized and evaluated for their inhibitory effects on the chemiluminescence and chemotactic activity of phagocytes in vitro. METHODS: The effects of the compounds on the respiratory burst of human whole blood and isolated human polymorphonuclear leukocytes (PMNs) were evaluated using a luminol-based chemiluminescence assay and their effect on chemotactic migration of PMNs was investigated using the Boyden chamber technique. KEY FINDINGS: Compounds 6, 17, 25 and 30 exhibited significant inhibitory activity on the oxidative burst of PMNs. The presence of methoxy groups at positions 2 and 5, and methoxylation and fluorination at positions 4 and 2 of both phenyl rings, respectively, may contribute significantly to their reactive oxygen species inhibition activity. Compounds 7, 17, 18, 24 and 32 showed strong inhibition of the chemotaxis migration of PMNs. Chlorination at various positions of both phenyl rings of cyclohexanone diarylpentanoid resulted in compounds with potent inhibitory effects on PMN migration. CONCLUSIONS: The results suggest that some of these diarylpentanoid analogues are able to modulate the innate immune response of phagocytes at different steps, emphasizing their potential as a source of new immunomodulatory agents. PMID- 22309273 TI - Effect of jatrorrhizine on delayed gastrointestinal transit in rat postoperative ileus. AB - OBJECTIVES: Postoperative ileus is major cause of postoperative complication and prolonged hospitalization. Jatrorrhizine, which is a protoberberine alkaloid isolated from the medicinal plants Berberis aristata and Coptis chinensis, has been found to increase contractility of gastric antral and ileum smooth muscles of rat gastrointestinal tract. We have investigated whether jatrorrhizine could offset gastrointestinal transit in rat with postoperative ileus. METHODS: Postoperative ileus was induced by laparotomy with intestinal manipulation under anaesthesia. Gastrointestinal transit was evaluated by measurement of gastric emptying, geometric centre and the migration of Evans blue. KEY FINDINGS: Postoperative ileus significantly delayed gastric emptying and intestinal transit. Jatrorrhizine dose-dependently (0.1, 0.3 and 1 mg/kg) offset delayed gastric emptying and intestinal transit (geometric centre and the migration of Evans blue) in postoperative ileus. Pretreatment of animals with atropine inhibited the action of jatrorrhizine on gastric emptying and intestinal transit, but pretreatment of animals with SB204070 did not influence the effect of jatrorrhizine on gastric emptying and intestinal transit in postoperative ileus. CONCLUSIONS: Jatrorrhizine offset postoperative ileus-induced delayed gastric emptying and intestinal transit in rats, an action mediated via the cholinergic pathway, but not involving activation of 5-HT(4) receptors. PMID- 22309274 TI - A mixture of Trachelospermi caulis and Moutan cortex radicis extracts suppresses collagen-induced arthritis in mice by inhibiting NF-kappaB and AP-1. AB - OBJECTIVES: We aimed to determine the anti-arthritis effect and its mechanism of a combination of herbal extracts from Trachelospermi caulis (TC) and Moutan cortex radicis (MC) (TCMC). METHODS: The anti-arthritis activity of TCMC was assessed using a mouse model of type II collagen-induced arthritis (CIA). Reverse transcriptase-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), electrophoretic mobility shift assay (EMSA) and other biological assays were performed. KEY FINDINGS: TCMC significantly ameliorated various inflammatory parameters, such as clinical arthritis index, histological deformation of joints, serum levels of rheumatoid arthritis biomarkers (cartilage oligomeric matrix protein, serum amyloid P and anti-collagen type II IgG antibody), and Th1-related responses (T cell proliferation, and production of Interferon-gamma and interleukin (IL)-2 in splenocytes isolated from CIA mice). The production of matrix metalloproteinases (MMPs), pro-inflammatory cytokines (tumour necrosis factor-alpha, IL-1beta and IL-6) and chemokines (macrophage inflammatory protein-1, monocyte chemoattractant protein-1, and Regulated upon Activation, Normal T-cell Expressed, and Secreted) was suppressed by TCMC in CIA mice. In addition, the number of osteoclasts in the hind tibia was significantly decreased. With regard to the mechanism, TCMC suppressed the activation of the transcription factors nuclear factor (NF)-kappaB and activator protein (AP)-1. CONCLUSIONS: TCMC exerts an anti-arthritis effect in CIA mice by suppression of the production of various inflammatory factors and the formation of osteoclasts through the inhibition of NF-kappaB and AP-1 activation. PMID- 22309275 TI - Anti-apoptotic effects of tamarind leaves against ethanol-induced rat liver injury. AB - OBJECTIVES: The leaf decoctions of Tamarindus indica (TI) have long been traditionally used in liver ailments. The aim of this study was to investigate the anti-apoptotic activity of TI leaf extract against acute ethanol (EtOH) induced liver injury. The major constituents of the extract were also examined for standardization purposes. METHODS: Rats (n = 5-7) were orally pretreated with TI leaf extract (25, 50 and 100 mg/kg) for seven days. Silymarin was used as a positive control. Liver tissue biochemical assays included key markers of apoptosis and its redox signalling. Serum enzyme levels were also determined. KEY FINDINGS: All graded doses of TI leaf extract mitigated the EtOH-induced liver caspase-3 activation (42, 57 and 64%) as well as DNA fragmentation (32, 47 and 50%), respectively. The highest dose of the extract demonstrated membrane stabilizing (38%) in addition to glutathione-replenishing (88%) effects. Also, the leaves improved the liver histopathological alterations. Moreover, major plant bioactive polyphenolics, that might be responsible for the extract's observed effects, were isolated and identified. CONCLUSIONS: TI leaf extract demonstrated promising anti-apoptotic hepatoprotective effects in rats. The use of TI leaves in different liver diseases, having apoptosis as the underlying pathology, hence warrants further clinical investigation. PMID- 22309276 TI - In-vivo laxative and toxicological evaluation and in-vitro antitumour effects of Mitracarpus frigidus aerial parts. AB - OBJECTIVES: To evaluate the in-vitro antitumour properties, and the in-vivo laxative and toxicological effects of the methanolic extract of the aerial parts of Mitracarpus frigidus (MFM). METHODS: The in-vitro antitumour activity of MFM was evaluated against three human tumour cell lines: Jurkat, HL60 and MCF-7. The laxative activity and the effect of MFM on intestinal motility were evaluated in rats at the doses of 100, 300 and 1000 mg/kg. Acute oral toxicity was performed at 10, 100, 1000 and 2000 mg/kg and subchronic toxicity was evaluated at 100, 300 and 1000 mg/kg of MFM during a 42-day period. After subchronic administration of MFM the biochemical, haematological and histopathological parameters were analysed. Also, the total content of anthraquinones was determined. KEY FINDINGS: MFM was cytotoxic only against HL60 and Jurkat cells with 89 and 83% growth inhibition, respectively. The laxative activity of MFM was similar to bisacodyl. Regarding the effect on intestinal motility, MFM showed a significant increase in the pathway of charcoal compared with the group treated with saline. Furthermore, MFM showed no in-vivo toxicity at the doses tested. Free and anthraquinone C- and O-glycosides were detected in MFM. CONCLUSIONS: MFM showed significant antitumour activity for leukaemic cells. Moreover, it presented laxative potential and no in vivo toxicity. PMID- 22309277 TI - Primary human sinonasal epithelial cell culture model for topical drug delivery in patients with chronic rhinosinusitis with nasal polyposis. AB - OBJECTIVES: The primary human sinonasal epithelial cell culture (HSNEC) allows for in-vitro modelling of mucosal responses to topical therapy. Cultures grown from healthy donors may underestimate changes in individuals with chronic sinonasal disease thereby yielding inaccurate results with respect to this large patient population. The purpose of this study was to analyse HSNECs derived from patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) to determine whether expected disease dependent variables salient to topical drug delivery persist in culture. METHODS: Cultures were grown from patients with CRSwNP. Ciliary beat frequency (CBF) (basal and stimulated), permeability (trans and paracellular), inflammatory response, and glucocorticoid dose response were measured and compared with healthy controls. KEY FINDINGS: Methylcholine stimulated CBF was greater in CRSwNP versus controls (DeltaCBF(60 min) 7.25 +/- 1.02 vs 0.89 +/- 1.04 Hz, respectively). Paracellular permeability was greater in CRSwNP versus controls (basolateral dextran(120 min) 18.97 +/- 3.90 vs 11.31 +/- 4.35 ug/ml, respectively). Lipopolysaccharide (0.1 mg/ml) stimulated interleukin 6 (IL-6) and IL-8 secretion was increased in CRSwNP versus controls (IL-6 Deltabaseline 1738.72 +/- 654.82 vs 1461.61 +/- 533.51%, respectively; IL-8 Deltabaseline 137.11 +/- 0.83 vs 111.27 +/- 0.67%, respectively). CRSwNP cultures were more sensitive than controls to dexamethasone (1 ug/ml) dependent IL-6 and IL-8 suppression. CONCLUSIONS: HSNECs derived from patients with CRSwNP retained their primary phenotype with respect to ciliary function, epithelial permeability, irritant induced inflammatory cytokine secretion, and glucocorticoid dose response. PMID- 22309279 TI - Iridium-catalyzed allylic alkylation reaction with N-aryl phosphoramidite ligands: scope and mechanistic studies. AB - A series of N-aryl phosphoramidite ligands has been synthesized and applied to iridium-catalyzed allylic alkylation reactions, offering high regio- and enantioselectivities for a wide variety of substrates. These ligands feature the synthetic convenience and good tolerance of the ortho-substituted cinnamyl carbonates. Mechanistic studies, including DFT calculations and X-ray crystallographic analyses of the (pi-allyl)-Ir complexes, reveal that the active iridacycle is formed via C(sp(2))-H bond activation. PMID- 22309278 TI - Recombination adenovirus-mediated human lactoferrin cDNA inhibits the growth of human MCF-7 breast cancer cells. AB - OBJECTIVES: Human lactoferrin, an 80 kDa iron-binding glycoprotein, has antitumour effects. We have explored the potential therapeutic role of re expressing human lactoferrin gene product in human breast cancer. METHODS: A recombinant adenovirus expressing the human lactoferrin cDNA (ad-hLTF) was constructed and used to infect breast cancer cells. KEY FINDINGS: Seventy-two hours after infection, ad-hLTF had considerable cytotoxicity on MCF-7 cells. A time-course study showed that ad-hLTF infection of MCF-7 cells at 100 plaque forming units per cell increased the number of cells in G(0) /G(1) phase and appeared markedly at Sub-G(1) apoptotic peak. The presence of apoptotic cells was confirmed using Annexin V-fluoresecein isothiocyanate apoptosis detection by flow cytometry. Ad-hLTF also resulted in a decrease of Bcl-2 protein and an increase in Bax protein. CONCLUSIONS: Ad-hLTF plays an important role in the induction of cell cycle arrest and apoptosis in MCF-7 cells. The results demonstrated that ad hLTF could have potential benefits in the treatment of breast cancer. PMID- 22309280 TI - Development of phytophotodermatitis in two cases related to Plantago lanceolata. AB - Plantago lanceolata, also known as snake's tongue, is a perennial herbaceous plant from the family Plantaginaceae. It is a species widely distributed both in Turkey and all over the world. Today, its fresh leaves are still used to soothe and suppress cough, externally for wound healing and draining abscesses. Phytophotodermatitis (PPD) is a dermal photosensitive reaction induced by the contact to or oral intake of a plant and subsequent exposure to sunlight. Its acute course is called phototoxic. In this paper, two cases developed phototoxic reaction with the consumption of Plantago lanceolata and subsequent exposure to the sunlight. These cases were presented since such effect of the plant has not been known previously and there is no resembling case in the literature. PMID- 22309281 TI - Angioedema after intravitreal bevacizumab injection. AB - A 47-year-old male with a history of diabetes mellitus type 2 exhibited with decreased vision in both eyes. The diagnosis of cystoid macular edema (CME) was made and it was decided to administer bilateral intravitreal bevacizumab (Avastin) injections. After intravitreal bevacizumab injection (1.25 mg/0.05 cc) to the right eye the patient had angioedema and conjunctival chemosis in the right eye which resolved in 48 h. One month later the left eye received intravitreal bevacizumab injection under the same conditions. Thirty minutes after the injection angioedema and conjunctival chemosis occurred in the left eye in which the signs and symptoms improved in 48 h. This report is the first one which describes angioedema after intravitreal bevacizumab injection. Care should be taken against the systemic hypersensitivity reactions when planned to receive intravitreal bevacizumab injection. PMID- 22309282 TI - Basic fibroblast growth factor modulates cell cycle of human umbilical cord derived mesenchymal stem cells. AB - BACKGROUND: Mesenchymal stem cells (MSC) have great potential in regenerative medicine, immunotherapy and gene therapy due to their unique properties of self renewal, high plasticity, immune modulation and ease for genetic modification. However, production of MSC at sufficient clinical scale remains an issue as in vitro generation of MSC inadequately fulfils the demand with respect to patients. OBJECTIVES: This study has aimed to establish optimum conditions to generate and characterize MSC from human umbilical cord (UC-MSC). MATERIALS AND METHODS: To optimize MSC population growth, basic fibroblast growth factor (bFGF) was utilized in culture media. Effects of bFGF on expansion kinetics, cell cycle, survival of UC-MSC, cytokine secretion, expression of early stem-cell markers and immunomodulation were investigated. RESULTS: bFGF supplementation profoundly enhanced UC-MSC proliferation by reducing population doubling time without altering immunophenotype and immunomodulatory function of UC-MSC. However, cell cycle studies revealed that bFGF drove the cells into the cell cycle, as a higher proportion of cells resided in S phase and progressed into M phase. Consistent with this, bFGF was shown to promote expression of cyclin D proteins and their relevant kinases to drive UC-MSC to transverse cell cycle check points, thus, committing the cells to DNA synthesis. Furthermore, supplementation with bFGF changed the cytokine profiles of the cells and reduced their apoptotic level. CONCLUSION: Our study showed that bFGF supplementation of UC-MSC culture enhanced the cells' growth kinetics without compromising their nature. PMID- 22309284 TI - Lack of dystrophin in mdx mice modulates the expression of genes involved in neuron survival and differentiation. AB - Duchenne muscular dystrophy is an X-linked disease characterized by progressive and lethal muscular wasting. Dystrophic patients, however, are also afflicted by several neurological disorders, the importance of which is generally underestimated. As promising therapies for muscles are currently in clinical trial stages, with the potential to provide an increase in the lifespan of young patients, determination of the genetic and molecular aspects characterizing this complex disease is crucial in order to allow the development of therapeutic approaches specifically designed for the nervous system. In this study, differences in gene expression in the superior cervical ganglion of postnatal day (P)5, P10 and 6-7-week-old wild-type and genetically dystrophic mdx mice were evaluated by DNA microarray analysis. The main aim was to verify whether the lack of dystrophin affected the transcript levels of genes related to different aspects of neuron development and differentiation. Ontological analysis of more than 500 modulated genes showed significant differences in genetic class enrichment at each postnatal date. Upregulated genes mainly fell in the categories of vesicular trafficking, and cytoskeletal and synaptic organization, whereas downregulated genes were associated with axon development, growth factors, intracellular signal transduction, metabolic processes, gene expression regulation, synapse morphogenesis, and nicotinic receptor clustering. These data strongly suggest that the structural and functional alterations previously described in both the autonomic and central nervous systems of mdx mice with respect to wild-type mice and related to crucial aspects of neuron life (i.e. postnatal development, differentiation, and plasticity) result not only from protein post-translational modifications, but also from direct and/or indirect modulation of gene expression. PMID- 22309283 TI - Therapeutic strategies to deplete macrophages in atherosclerotic plaques. AB - Macrophages can be found in all stages of atherosclerosis and are major contributors of atherosclerotic plaque development, progression and destabilization. Continuous recruitment of monocytes drives this chronic inflammatory disease, which can be intervened by several strategies: reducing the inflammatory stimulus by lowering circulating lipids and promoting cholesterol efflux from plaque, direct and indirect targeting of adhesion molecules and chemokines involved in monocyte adhesion and transmigration and inducing macrophage death in atherosclerotic plaques in combination with anti-inflammatory drugs. This review discusses the outlined strategies to deplete macrophages from atherosclerotic plaques to promote plaque stabilization. PMID- 22309285 TI - Comparison of central and intraesophageal factors between gastroesophageal reflux disease (GERD) patients and those with GERD-related noncardiac chest pain. AB - Gastroesophageal reflux disease (GERD) causes a wide range of symptoms. Some patients present with typical symptoms such as heartburn and regurgitation and others with atypical symptoms such as chest pain. The mechanism responsible for the varying clinical presentation of GERD is still not fully elucidated. The aim of this study was to prospectively evaluate differences in central and local intraesophageal factors between patients with typical GERD symptoms and those with noncardiac chest pain (NCCP). Patients presenting with typical and atypical symptoms suspicious of GERD underwent upper endoscopy and 24-hour pH monitoring with four sensors, each positioned at a different esophageal level. All patients completed GERD symptom, Hospital Anxiety and Depression Scale, and Symptom Stress Rating questionnaires. From January 2006 to December 2009, 50 patients were recruited, 29 with typical symptoms, and 21 with NCCP. Patients with proven GERD and NCCP had higher proximal extension of acid during reflux episodes than patients with typical symptoms. They were found to be older, had a shorter history of symptom onset, worse anxiety scores, and more endoscopic findings compatible with gastritis. Proximal extension of acid during the reflux episodes in patients with GERD presenting with NCCP may play a role in symptom generation. PMID- 22309287 TI - A case of dual atrioventricular nodal nonreentrant tachycardia(DAVNNT) in the EP Rounds. PMID- 22309286 TI - Glucocorticoid-induced tumour necrosis factor receptor expression: a potential molecular link between steroid intake and complicated diverticulitis? AB - AIM: Immunosuppression and steroid medication have been identified as risk factors for complicated sigmoid diverticulitis. The underlying molecular mechanisms have not yet been elucidated. We hypothesized that glucocorticoid induced tumour necrosis factor receptor (GITR) and matrix metalloproteinase-9 (MMP-9) might play a role. METHOD: GITR and MMP-9 were analysed at protein [immunohistochemistry/immunofluorescence (IF)] and messenger RNA level (real-time polymerase chain reaction) in surgical specimens with complicated and non complicated diverticulitis (n=101). IF double staining and regression analysis were performed for both markers. GITR expression was correlated with clinical data and its usefulness as a diagnostic test was investigated. RESULTS: High GITR expression (>=41%) was observed in the inflammatory infiltrate in complicated diverticulitis, in contrast to non-complicated diverticulitis where GITR expression was low (P<0.001). High GITR expression was significantly associated with steroid use and pulmonary diseases (both P<0.001). MMP-9 expression correlated with GITR expression (R(2) =0.7268, P<0.0001, r=0.85) as demonstrated with IF double-staining experiments. Co-labelling of GITR with CD68, but not CD15, suggested that GITR-expressing cells in diverticulitis are macrophages. GITR expression was superior to C-reactive protein (CRP), white cell count and temperature in distinguishing complicated and non-complicated diverticulitis. CONCLUSIONS: Our results suggest that GITR expression in inflammatory cells might potentially indicate a molecular link between steroid use and complicated forms of acute sigmoid diverticulitis. Increased MMP-9 expression by GITR signalling might explain the morphological changes in the colonic wall of perforated and phlegmonous diverticulitis. Analysis of soluble GITR might be a promising strategy for future research. PMID- 22309288 TI - Spatial variation in egg size and egg number reflects trade-offs and bet-hedging in a freshwater fish. AB - 1. Maternal reproductive investment is thought to reflect a trade-off between offspring size and fecundity, and models generally predict that mothers inhabiting adverse environments will produce fewer, larger offspring. More recently, the importance of environmental unpredictability in influencing maternal investment has been considered, with some models predicting that mothers should adopt a diversified bet-hedging strategy whilst others a conservative bet hedging strategy. 2. We explore spatial egg size and fecundity patterns in the freshwater fish southern pygmy perch (Nannoperca australis) that inhabits a diversity of streams along gradients of environmental quality, variability and predictability. 3. Contrary to some predictions, N. australis populations inhabiting increasingly harsh streams produced more numerous and smaller eggs. Furthermore, within-female egg size variability increased as environments became more unpredictable. 4. We argue that in harsh environments or those prone to physical disturbance, sources of mortality are size independent with offspring size having only a minor influence on offspring fitness. Instead, maternal fitness is maximized by producing many small eggs, increasing the likelihood that some offspring will disperse to permanent water. We also provide empirical support for diversified bet-hedging as an adaptive strategy when future environmental quality is uncertain and suggest egg size may be a more appropriate fitness measure in stable environments characterized by size-dependent fitness. These results likely reflect spatial patterns of adaptive plasticity and bet hedging in response to both predictable and unpredictable environmental variance and highlight the importance of considering both trait averages and variance. 5. Reproductive life-history traits can vary predictably along environmental gradients. Human activity, such as the hydrological modification of natural flow regimes, alters the form and magnitude of these gradients, and this can have both ecological and evolutionary implications for biota adapted to now non-existent natural environmental heterogeneity. PMID- 22309289 TI - Akt augments the oncogenic potential of the HBx protein of hepatitis B virus by phosphorylation. AB - Hepatitis B virus X protein (HBx) is a putative viral oncoprotein that plays an important role in various cellular processes, including modulation of the phosphatidylinositol 3-kinase/Akt signalling pathway. However, the molecular mechanism of Akt activation remains elusive. Here we show that HBx interacts with Akt1 kinase and is phosphorylated at serine 31 as indicated by mutational analysis of the Akt recognition motif (creating the HBxS31A mutant) or immunoblotting of HBx immunoprecipitates using Akt motif-specific antibody. The Akt-dependent phosphorylation of HBx was abrogated in the presence of the phosphatidylinositol 3-kinase inhibitor LY294002 or Akt1 gene silencing by specific siRNA. Co-immunoprecipitation studies provided evidence for HBx-Akt interaction in a cellular environment. This interaction was also confirmed in hepatoma HepG2.2.15 cells in which HBx was expressed at physiological levels from the integrated hepatitis B viral genome. The HBx-Akt interaction was essential for Akt signalling, and involved displacement of the Akt-bound negative regulator 'C-terminal modulator protein' by HBx. HBx-activated Akt phosphorylated its downstream target glycogen synthase kinase 3beta, leading to stabilization of beta-catenin, while p65 phosphorylation resulted in enhanced promoter recruitment and expression of target genes encoding cyclin D1 and Bcl-XL. Further, the oncogenic potential of HBx was significantly augmented in the presence of Akt in a soft agar colony formation assay. Together, these results suggest that oncogenic co-operation between HBx and Akt may be important for cell proliferation, abrogation of apoptosis and tumorigenic transformation of cells. PMID- 22309290 TI - Nursing care for patients on the edge of life in nursing homes: obstacles are overshadowing opportunities. AB - BACKGROUND: Patients in nursing homes have comprehensive needs for nursing care and medical treatment. Most patients benefit from the treatment, but some are 'on the edge of life'-in a borderland between living and dying with an unpredictable outcome, and questions are sometimes raised whether to withhold/withdraw curative treatment. AIM: The aim was to describe nurses' conceptions of good nursing care, and how this could be carried out for patients on the edge of life in nursing homes. DESIGN: In order to discover variations in the nurses' understandings a phenomenographic approach was chosen. Phenomenography is concerned with qualitatively different ways of conceiving a phenomenon. Methods. Fourteen nurses from two nursing homes were individually interviewed twice. A phenomenographic analysis was used. RESULTS: The outcome-space included two main categories. The first, 'good nursing care is to meet patients' needs for dignity,' included three description-categories: needs for 'preparedness', 'human relationship' and 'bodily comfort and safety'. The second, 'opportunities were overshadowed by obstacles' in carrying out nursing care encompassed three description-categories: 'organisational factors,''relational factors' and 'personal factors'. CONCLUSIONS: This study shows nurses' conceptions of the importance of good nursing care for comforting patients on the edge of life. IMPLICATIONS FOR PRACTICE: Several obstacles related to resources, communication, cooperation and nurses' professional strength and power need to be overcome if good nursing care can be performed. PMID- 22309291 TI - Hand hygiene practices of veterinary support staff in small animal private practice. AB - OBJECTIVE: To evaluate the hand hygiene (HH) practices among veterinary technicians (VT) and veterinary support staff (VSS) in small animal private practice. METHODS: This was a prospective questionnaire-based study involving 182 VT and VSS from 18 small animal hospitals in the USA. Questions asked included gender, number of animals handled per work shift, frequency of hand washing, reason for not washing more frequently, most common available hand washing agent, education regarding the importance of HH and frequency of ring wearing. RESULTS: Less than half of the respondents [76 of 182 (41.7%)] reported washing their hands regularly between handling patients and 154 of 182 (85.6%) believed they should have washed more frequently. The most commonly employed HH agent was hand soap [154 of 182 (84.6%)] and the most common reason cited for not washing more frequently was being too busy [132 of 182 (72.5%)]. Only 96 of 182 (52.7%) respondents were educated by doctors at their hospital regarding the importance of HH. CLINICAL SIGNIFICANCE: The HH practices among VT and VSS in small animal private practice is poor. Hand soap was the most commonly employed agent among respondents in this study. Education of VT and VSS regarding the importance of HH requires improvement. PMID- 22309292 TI - The association of nutritional assessment criteria with health-related quality of life in patients with advanced colorectal carcinoma. AB - Health-related quality of life (QoL) is a goal in nutritional oncology but the association between nutritional status and QoL is rarely explored. The aim of the study was to investigate the association of nutritional assessment criteria with QoL in 50 patients with advanced colorectal carcinoma. A second aim was to investigate changes in body weight and QoL during a 3-month follow-up. Muscle mass, nutritional risk, malnutrition and cachexia according to three different criteria were assessed, as well as health-related QoL. At inclusion, 36 patients experienced weight loss, 10 patients sarcopenia, 25 were at nutritional risk, 16 were malnourished and 11, 14 and 31 patients had cachexia according to different criteria. All nutritional assessment criteria discriminated between groups of patients with worse or better QoL to varying degrees. Malnutrition and cachexia defined by the European Palliative Care Research Collaborative and adjusted for recent gain or stabilisation of body weight discriminated on most QoL scores. Weight loss at follow-up was associated with a decrease in several QoL scores. Recognition of weight loss as well as diagnosing malnutrition and cachexia should be the first steps in an interventional pathway to enhance nutritional status and QoL in patients with advanced colorectal carcinoma. PMID- 22309293 TI - Fine-tuning the pH trigger of self-assembly. AB - The creation of smart, self-assembling materials that undergo morphological transitions in response to specific physiological environments can allow for the enhanced accumulation of imaging or drug delivery agents based on differences in diffusion kinetics. Here, we have developed a series of self-assembling peptide amphiphile molecules that transform either isolated from molecules or spherical micelles into nanofibers when the pH is slightly reduced from 7.4 to 6.6, in isotonic salt solutions that simulate the acidic extracellular microenvironment of malignant tumor tissue. This transition is rapid and reversible, indicating the system is in thermodynamic equilibrium. The self-assembly phase diagrams show a single-molecule-to-nanofiber transition with a highly concentration-dependent transition pH. However, addition of a sterically bulky Gd(DO3A) imaging tag on the exterior periphery shifts this self-assembly to more acidic pH values and also induces a spherical micellar morphology at high pH and concentration ranges. By balancing the attractive hydrophobic and hydrogen-bonding forces, and the repulsive electrostatic and steric forces, the self-assembly morphology and the pH of transition can be systematically shifted by tenths a pH unit. PMID- 22309294 TI - Keeping nurse researchers safe: workplace health and safety issues. AB - AIM: This article is a report of a qualitative study of workplace health and safety issues in nursing research. BACKGROUND: Researcher health and safety have become increasing concerns as there is an increased amount of research undertaken in the community and yet there is a lack of appropriate guidelines on how to keep researchers safe when undertaking fieldwork. DESIGN: This study employed a descriptive qualitative approach, using different sources of data to find any references to researcher health and safety issues. METHODS: A simple descriptive approach to inquiry was used for this study. Three approaches to data collection were used: interviews with 15 researchers, audits of 18 ethics applications, and exploration of the literature between 1992 and 2010 for examples of researcher safety issues. Data analysis from the three approaches identified participant comments, narrative descriptions or statements focused on researcher health and safety. RESULTS: Nurse researchers' health and safety may be at risk when conducting research in the community. Particular concern involves conducting sensitive research where researchers are physically at risk of being harmed, or being exposed to the development of somatic symptoms. Nurse researchers may perceive the level of risk of harm as lower than the actual or potential harm present in research. Nurse researchers do not consistently implement risk assessment before and during research. CONCLUSIONS: Researcher health and safety should be carefully considered at all stages of the research process. Research focusing on sensitive data and vulnerable populations need to consider risk minimization through strategies such as appropriate researcher preparation, safety during data collection, and debriefing if required. PMID- 22309295 TI - Comparison of analog 2D and digital 3D preoperative templating for predicting implant size in total knee arthroplasty. AB - The aim of this study was to compare the accuracy of preoperative templating in total knee arthroplasty (TKA) using conventional two-dimensional (2D) and computed tomography (CT)-based three-dimensional (3D) procedures, and to confirm the necessity of 3D evaluation for preoperative planning. One hundred consecutive primary TKAs were analyzed. Preoperative templating was performed for each TKA using both conventional 2D radiographs and a CT-based 3D image model created using KneeCAS software. Accuracies with regard to the predicted and actual implant sizes were determined for each procedure. The 3D procedure was found to be more accurate (59%) than the 2D procedure (56%) in predicting implant size, but the difference was not statistically significant (p = 0.67). Computer assisted surgery systems are often used for preoperative planning in TKA. However, our results do not support the superiority of 3D preoperative templating over 2D conventional evaluation in predicting implant size. Thus, 3D templating may not be necessary for preoperatively predicting implant size in TKA, and can only be used as an approximate guide. PMID- 22309296 TI - Sexual behaviour and neuronal activation in the vomeronasal pathway and hypothalamus of food-deprived male rats. AB - As feeding and mating are mutually-exclusive goal-orientated behaviours, we investigated whether brief food deprivation would impair the display of sexual behaviour of male rats. Analysis of performance in a sexual incentive motivation test revealed that, similar to fed males, food-deprived males preferred spending time in the vicinity of receptive females rather than nonreceptive females. Despite this, food-deprived males were more likely to be slow to mate than normally-fed males, and a low dose of the satiety peptide alpha-melanocyte stimulating-hormone attenuated the effect of hunger. Using Fos immunocytochemistry, we compared neuronal activity in the vomeronasal projection pathway in response to oestrous cues from receptive females between food-deprived and fed males. As in fed males, more Fos expression was seen in the rostral part of the bed nucleus of the stria terminalis and in the medial preoptic area in food-deprived males, confirming that food-deprived males can recognise and respond to female oestrous cues. However, although there was also an increase in Fos expression in the bed nucleus of the accessory tract and in the posteromedial amygdala in fed males, no increases were seen in these areas in food-deprived rats. We also found selective attenuation in the activation of lateral posterior paraventricular nucleus (lpPVN) oxytocin neurones in food-deprived males. Taken together, the data show that, although food-deprived males can still become sexually motivated, copulation is delayed, and this is accompanied by variations in neuronal activity in the vomeronasal projection pathway. We propose that, in hungry rats, the lpPVN oxytocin neurones (which project to the spinal cord and are involved in maintaining penile erection) facilitate the transition from motivation to intromission, and their lack of activation impairs intromission, and thus delays mating. PMID- 22309297 TI - Postpartum rupture of the posteromedial papillary muscle. AB - We report a case of postpartum severe mitral regurgitation caused by papillary muscle rupture in a female with normal coronary arteries. The etiology of papillary muscle rupture was endocarditis from puerperal fever. Clinical stabilization was achieved with extracorporeal membrane oxygenation (ECMO) followed by mitral valve replacement two days later. PMID- 22309298 TI - Challenges to successful breastfeeding. PMID- 22309299 TI - Comment on "Breastfeeding--so easy even a doctor can support it". PMID- 22309300 TI - Protocol authorship. PMID- 22309303 TI - Near elimination of ventricular pacing in SafeR mode compared to DDD modes: a randomized study of 422 patients. AB - AIMS: SafeR performance versus DDD/automatic mode conversion (DDD/AMC) and DDD with a 250-ms atrioventricular (AV) delay (DDD/LD) modes was assessed toward ventricular pacing (Vp) reduction. METHODS: After a 1-month run-in phase, recipients of dual-chamber pacemakers without persistent AV block and persistent atrial fibrillation (AF) were randomly assigned to SafeR, DDD/AMC, or DDD/LD in a 1:1:1 design. The main endpoint was the percentage of Vp (%Vp) at 2 months and 1 year after randomization, ascertained from device memories. Secondary endpoints include %Vp at 1 year according to pacing indication and 1-year AF incidence based on automatic mode switch device stored episodes. RESULTS: Among 422 randomized patients (73.2+/-10.6 years, 50% men, sinus node dysfunction 47.4%, paroxysmal AV block 30.3%, bradycardia-tachycardia syndrome 21.8%), 141 were assigned to SafeR versus 146 to DDD/AMC and 135 to DDD/LD modes. Mean %Vp at 2 months was 3.4+/-12.6% in SafeR versus 33.6+/-34.7% and 14.0+/-26.0% in DDD/AMC and DDD/LD modes, respectively (P<0.0001 for both). At 1 year, mean %Vp in SafeR was 4.5+/-15.3% versus 37.9+/-34.4% and 16.7+/-28.0% in DDD/AMC and DDD/LD modes, respectively (P<0.0001 for both). The proportion of patients in whom Vp was completely eliminated was significantly higher in SafeR (69%) versus DDD/AMC (15%) and DDD/LD (45%) modes (P<0.0001 for both), regardless of pacing indication. The absolute risk of developing permanent AF or of remaining in AF for >30% of the time was 5.4% lower in SafeR than in the DDD pacing group (ns). CONCLUSIONS: In this selected patient population, SafeR markedly suppressed unnecessary Vp compared with DDD modes. PMID- 22309304 TI - Laparoscopic adhesiolysis: consensus conference guidelines. AB - AIM: Laparoscopic adhesiolysis has been demonstrated to be technically feasible in small bowel obstruction and carries advantages in terms of post-surgical course. The increasing dissemination of laparoscopic surgery in the emergency setting and the lack of concrete evidence in the literature have called for a consensus conference to draw recommendations for clinical practice. METHODS: A literature search was used to outline the evidence, and a consensus conference was held between experts in the field. A survey of international experts added expertise to the debate. A public jury of surgeons discussed and validated the statements, and the entire process was reviewed by three external experts. RESULTS: Recommendations concern the diagnostic evaluation, the timing of the operation, the selection of patients, the induction of the pneumoperitoneum, the removal of the cause of obstructions, the criteria for conversion, the use of adhesion-preventing agents, the need for high-technology dissection instruments and behaviour in the case of misdiagnosed hernia or the need for bowel resection. CONCLUSION: Evidence of this kind of surgery is scanty because of the absence of randomized controlled trials. Nevertheless laparoscopic skills in emergency are widespread. The recommendations given with the consensus process might be a useful tool in the hands of surgeons. PMID- 22309305 TI - Reduced serum uric acid levels in neuromyelitis optica: serum uric acid levels are reduced during relapses in NMO. AB - OBJECTIVES: Uric acid (UA), a product of purine metabolism, is known to be reduced in patients with various neurological disorders including multiple sclerosis (MS). However, it has still remained unclear whether there is a close relationship between UA and neuromyelitis optica (NMO). The aim of this study was to investigate the association between serum UA levels and disease activity in NMO. METHODS: Retrospective analysis was made of blood samples during relapses (n = 48) and during stable disease (n = 49) from 20 patients with NMO. As controls, 59 blood samples during relapses from 39 patients with MS and 90 samples from healthy subjects were obtained. Spine magnetic resonance images (MRIs) performed during relapses (n = 24) in NMO were analysed. RESULTS: The results indicated that UA levels during relapses in NMO were significantly lower compared to healthy subjects (P < 0.01), but not different from those during relapses in MS, and that reduced UA levels during relapses in NMO were normalized during stable disease. However, UA levels during relapses were not correlated with Gd enhancement in spine MRI. CONCLUSION: UA levels are associated with clinical disease status in patients with NMO. Further investigations are recommended to elucidate the role of UA as a biomarker of disease activity in NMO. PMID- 22309306 TI - Serum- and glucocorticoid-dependent kinase-1-induced cell migration is dependent on vinculin and regulated by the membrane androgen receptor. AB - The serum- and glucocorticoid-dependent kinases 1-3 (SGK1-3) are downstream effectors of phosphatidylinositol 3-kinases, implicated in various cell responses including colon cancer tumorigenesis in mice. Here, we investigated the role of SGK1 in the regulation of cell motility. Using Caco-2 colon tumor and HEK293 embryonic kidney cells, we report that transfection with the constitutively active SGK1 mutant (SGK1-SD) significantly enhanced cell motility. The cell adhesion protein vinculin was effectively dephosphorylated in SGK1-SD-transfected cells. Treatment of the cells with phosphatase inhibitors restored vinculin phosphorylation and inhibited cell migration, indicating a significant role for vinculin phosphorylation in SGK1-induced motility. SGK1-SD-enhanced cell motility was inhibited by activation of membrane androgen-binding sites (mAR) via testosterone-conjugates in both cell lines, whereas intracellular androgen receptor (iAR)-silencing and flutamide treatment revealed that these effects were clearly independent of the interaction of SGK1 with the classical androgen receptors (iAR). More importantly, mAR activation restored vinculin phosphorylation in SGK1-SD-transfected cells, whereas silencing of vinculin fully reversed the mAR-induced inhibition of the migratory capacity, implying that this protein is directly involved in cell motility regulation by SGK1 and mAR. This study indicates for the first time that SGK1 regulates cell migration via vinculin dephosphorylation, a mechanism that is controlled by mAR function. PMID- 22309307 TI - Formation of tubular scrolls with controlled internal cavity. AB - In this work, we investigate internal cavity controlled tubular scroll formation through simple modification of tether coils that are grafted on the surface of a 2D polymer sheet. Dissipative particle dynamics simulations show that coarse grained 2D sheets transform to various cylindrical structures including tubular and filled scrolls in the presence of broken volume and chemical symmetries of tether coils: volume (chemical) asymmetry arises when coils on one side have a different number of beads (solvent affinity) from those on the other side. It is clear from a phase diagram that the scroll formation is governed by the balance between hydrophobicity and entropy of coils. The density profiles show that a wide range of interior cavity diameter can be obtained by employing volume asymmetry on coils with weak chemical asymmetry. We provide crucial scientific insights in understanding the scroll formation through self-assembly of rod-coil molecules and suggest modification of the tether coil's properties as a practical and systematic method to form tubular scrolls with targeted internal cavity. PMID- 22309308 TI - Multi-professional communication for older people in transitional care: a review of the literature. AB - AIMS AND OBJECTIVES: To synthesise research-reporting literature about multi professional communication between health and social care professionals within transitional care for older people, with particular attention on outcomes, enabling contextual factors and constraints. BACKGROUND: Older adults experience high rates of morbidity and health care usage, and frequently transit between health services, and community and social care providers. These transition episodes place elders at increased risk of adverse incidents due to poor communication of information. Integrated multi-professional models of care built on enhanced communication have been widely promoted as a strategy to improve transitional care for older people. However, a range of findings exist in the literature to guide service providers and researchers. DESIGN: Comprehensive literature search and review strategies were employed to identify, describe and synthesise relevant studies. Ten databases were searched in addition to Google Scholar. CONCLUSIONS: Specified discharge worker roles, multi-professional care coordination teams, and information technology systems promote better service satisfaction and subjective quality of life for older people when compared with standard hospital discharge. Improved multi-professional communication reduces rates of re-admission and length of stay indicating greater cost effectiveness and efficiency for the health and social care systems. Systems of care emphasizing information exchange, education and negotiation between stakeholders facilitate communication in transitional care contexts for older adults. Conversely, lack of dialogue and lack of understanding of others' roles are barriers to communication in transitional care. IMPLICATIONS FOR PRACTICE: Enhanced multi-professional communication, transitional pathways, and role clarity are required to improve the quality, sustainability and responsiveness of aged care into the future. Recommendations for further research include: (i) Investigation of pathways promoting person-centred care planning including the older person, their family and relevant practitioners; (ii) Development of interventions aimed at improving multi-professional communication and transitional aged care with marginalised and socially disadvantaged elders on indicators of equity and access; (iii) Investigation of changing roles for practitioners in multi-professional teams with a focus on community-based teams including nurses specialising in aged care and general practice. PMID- 22309309 TI - Clinical simulation fidelity and nurses' identification of critical event risk: a signal detection analysis. AB - AIMS: This article is a report of a study exploring the effect of increasing fidelity on nurses' risk detection in clinical simulation and the effect of clinical experience on nurses' risk detection ability. BACKGROUND: Clinical environments can be recreated successfully using simulation. However, how judgement changes as simulation fidelity increases is unknown. Knowledge of the effects of increased fidelity on judgement may help in the design of educational interventions seeking to improve clinical judgement in nurses. DESIGN: Quasi experimental signal detection study. METHOD: During 2008-2009, using a quasi experimental signal detection design, 63 nursing students and 34 experienced nurses were presented with 25 paper and 25 human simulator 'cases' based on real patient records from a single UK National Health Service hospital. Nurses judged whether a simulated case was 'at risk' or 'not at risk' of a critical event. Clinical judgement performance was measured using standard signal detection measures. FINDINGS: Judgement performance, as measured by hit rates and signal detection ability were significantly lower in higher fidelity clinical simulations. False alarm rates and bias (beta) did not differ according to the fidelity of simulation. Clinical experience did not predict the ability to detect risk. CONCLUSION: As fidelity of simulation increased, both novice and experienced nurses' were less likely to be able to separate important clinical risk from clinical noise in a simulated clinical environment. PMID- 22309310 TI - Urinary globotriaosylsphingosine-related biomarkers for Fabry disease targeted by metabolomics. AB - Fabry disease is a lysosomal storage disorder caused by deficiency of alpha galactosidase A, resulting in glycosphingolipid accumulation in organs and tissues, including plasma and urine. Two disease-specific Fabry biomarkers have been identified and quantified in plasma and urine: globotriaosylceramide (Gb(3)) and globotriaosylsphingosine (lyso-Gb(3)). The search continues for biomarkers that might be reliable indicators of disease severity and response to treatment. The main objective of this study was to target other urinary biomarkers using a time-of-flight mass spectrometry metabolomic approach. Urinary metabolites of 63 untreated Fabry patients and 59 controls were analyzed. A multivariate statistical analysis performed on a subset of male samples revealed seven novel Fabry biomarkers in urine, all lyso-Gb(3) analogues having modified sphingosine moieties. The empirical formulas of the sphingosine modifications were determined by exact mass measurements (- C(2)H(4), - C(2)H(4) + O, - H(2), - H(2) + O, + O, + H(2)O(2), + H(2)O(3)). We evaluated the relative concentration of lyso-Gb(3) and its seven analogues by measuring area counts for each analogue in all Fabry patients. All samples were normalized to creatinine. We found higher concentrations for males with Fabry disease compared to females. None of these biomarkers were detected in controls. To our knowledge, this is the first time that lyso-Gb(3)-related Fabry disease biomarkers are detected in urine. PMID- 22309311 TI - Development and piloting of a brain tumour-specific question prompt list. AB - The objective of this research was to develop a question prompt list aimed at increasing question asking and reducing the unmet information needs of adults with primary brain tumours, and to pilot the question prompt list to determine its suitability for the intended population. Thematic analysis of existing resources was used to create a draft which was refined via interviews with 12 brain tumour patients and six relatives, readability testing and review by health professionals. A non-randomised before-after pilot study with 20 brain tumour patients was used to assess the acceptability and usefulness of the question prompt list, compared with a 'standard brochure', and the feasibility of evaluation strategies. The question prompt list developed covered seven main topics (diagnosis, prognosis, symptoms and changes, treatment, support, after treatment finishes and the health professional team). Pilot study participants provided with the question prompt list agreed that it was helpful (7/7), contained questions that were useful to them (7/7) and prompted them to ask their medical oncologist questions (5/7). The question prompt list is acceptable to patients and contains questions relevant to them. Research is now needed to assess its effectiveness in increasing question asking and reducing unmet information needs. PMID- 22309312 TI - Genomic selection for growth and wood quality in Eucalyptus: capturing the missing heritability and accelerating breeding for complex traits in forest trees. AB - * Genomic selection (GS) is expected to cause a paradigm shift in tree breeding by improving its speed and efficiency. By fitting all the genome-wide markers concurrently, GS can capture most of the 'missing heritability' of complex traits that quantitative trait locus (QTL) and association mapping classically fail to explain. Experimental support of GS is now required. * The effectiveness of GS was assessed in two unrelated Eucalyptus breeding populations with contrasting effective population sizes (N(e) = 11 and 51) genotyped with > 3000 DArT markers. Prediction models were developed for tree circumference and height growth, wood specific gravity and pulp yield using random regression best linear unbiased predictor (BLUP). * Accuracies of GS varied between 0.55 and 0.88, matching the accuracies achieved by conventional phenotypic selection. Substantial proportions (74-97%) of trait heritability were captured by fitting all genome-wide markers simultaneously. Genomic regions explaining trait variation largely coincided between populations, although GS models predicted poorly across populations, likely as a result of variable patterns of linkage disequilibrium, inconsistent allelic effects and genotype * environment interaction. * GS brings a new perspective to the understanding of quantitative trait variation in forest trees and provides a revolutionary tool for applied tree improvement. Nevertheless population-specific predictive models will likely drive the initial applications of GS in forest tree breeding. PMID- 22309313 TI - Parental depressive symptoms and children's sleep: the role of family conflict. AB - BACKGROUND: We used a multi-method and multi-informant design to identify developmental pathways through which parental depressive symptoms contribute to children's sleep problems. Environmental factors including adult inter-partner conflict and parent-child conflict were considered as process variables of this relation. METHODS: An ethnically and socioeconomically diverse sample of children (n = 268) participated (M age = 9.44 years, SD = 8.61 months). Children wore actigraphs for 7 consecutive nights and also reported on their sleep problems. RESULTS: Higher levels of maternal depressive symptoms were associated with children's sleep/wake problems. Higher levels of paternal depressive symptoms were associated with shorter time in bed and fewer sleep minutes. Inter-partner conflict and parent-child conflict were mechanisms of effects in the associations between maternal depressive symptoms and children's actigraphy-based and self-reported sleep problems. CONCLUSIONS: Findings build on this scant literature and highlight the importance of identifying pathways of risk and familial and environmental influences on children's sleep problems. PMID- 22309314 TI - Capture of sunflower seedlings lipase using polyclonal antibodies. AB - True lipolytic activity is observed in different subcellular fractions of germinating sunflower seedlings (Helianthus annuus L.) in delipidated oleosomes and microsomes. Triacylglycerol lipase (EC. 3.1.1.3) catalyses the first catabolic step of lipolysis. To our knowledge, this plant lipase has not yet been identified. Our aim was to develop a method to collect the lipase for further studies. An immunological method was used to capture sunflower seedling lipase from oleosomes and microsomes. This method uses an immunoaffinity column prepared with polyclonal antibodies (anti-P-61) directed against oleosomal activity. Our results verify that we have successfully adapted a purification procedure of plant lipase using anti-P-61. Since the eluted lipolytic activity is distributed among diverse proteic peaks, we changed the elution procedure: the introduction of CHAPS, a zwitterionic detergent, allowed us to recover all the lipolytic activity in a single proteic peak. This may help us to characterise the studied lipase. PMID- 22309315 TI - Matrix metalloproteinase (MMP)-2 and MMP-9 polymorphisms and haplotypes as disease biomarkers. AB - Chaudhary and colleagues observed associations of matrix metalloproteinase (MMP) 2 (-1306C/T) and MMP-9 (-1562C/T) promoter polymorphisms with head and neck squamous cell carcinoma (HNSCC), but not with oral submucous fibrosis (OSMF) in an Indian population. We suggest that they could carry out a haplotype analysis with their data on MMP-2 genotypes (-1306C/T and -168G/T) and that they consider genotyping the microsatellite -90 (CA)(14-24) in the MMP-9 promoter region in order to perform haplotype analysis in combination with their data on MMP-9 ( 1562C/T) polymorphism. These suggestions could provide additional information with clinical relevance to cancer susceptibility. PMID- 22309316 TI - Are emissions of black carbon from gasoline vehicles underestimated? Insights from near and on-road measurements. AB - Measurements of black carbon (BC) with a high-sensitivity laser-induced incandescence (HS-LII) instrument and a single particle soot photometer (SP2) were conducted upwind, downwind, and while driving on a highway dominated by gasoline vehicles. The results are used with concurrent CO(2) measurements to derive fuel-based BC emission factors for real-world average fleet and heavy-duty diesel vehicles separately. The derived emission factors from both instruments are compared, and a low SP2 bias (relative to the HS-LII) is found to be caused by a BC mass mode diameter less than 75 nm, that is most prominent with the gasoline fleet but is not present in the heavy-duty diesel vehicle exhaust on the highway. Results from both the LII and the SP2 demonstrate that the BC emission factors from gasoline vehicles are at least a factor of 2 higher than previous North American measurements, and a factor of 9 higher than currently used emission inventories in Canada, derived with the MOBILE 6.2C model. Conversely, the measured BC emission factor for heavy-duty diesel vehicles is in reasonable agreement with previous measurements. The results suggest that greater attention must be paid to black carbon from gasoline engines to obtain a full understanding of the impact of black carbon on air quality and climate and to devise appropriate mitigation strategies. PMID- 22309317 TI - Prevention of inappropriate ICD shocks due to lead insulation failure by continuous monitoring and automatic alert. AB - Patients with implantable cardioverter defibrillator lead insulation failures may present with oversensing and/or abnormal impedance. The Lead Integrity Alert (LIA) monitors right ventricular pace/sense leads using both continuous oversensing and daily impedance measurementd. Oversensing consists of isolated short R-R intervals and nonsustained runs of short R-R intervals. The LIA algorithm has been studied for Sprint Fidelis conductor fractures, but not for lead insulation failures. We report on a patient with a failed St. Jude RiataTM ST lead (St. Jude Medical, St. Paul, MN, USA) connected to a Medtronic Virtuoso DR (Medtronic Inc., Minneapolis, MN, USA) with the LIA. Oversensing triggered the LIA, while the impedance trend was normal. PMID- 22309319 TI - Lymphocyte subset analysis for the assessment of treatment-related complications after autologous stem cell transplantation in multiple myeloma. AB - BACKGROUND AIMS: The aim of this study was to investigate the correlation between infused lymphocyte populations and lymphocyte subsets at engraftment, and the early clinical implications of lymphocyte subset recovery after autologous stem cell transplantation (ASCT) in multiple myeloma (MM). METHODS: We examined the lymphocyte populations of infused autografts and the lymphocyte subsets of peripheral blood at engraftment from 50 patients using flow cytometry. Each subset was grouped as low (below median) and high (above median) to examine the correlation with mucositis of grade 3 or more and the occurrence of infections and cytomegalovirus (CMV) reactivation. RESULTS: Using Spearman correlation coefficients, we found that cell doses of infused CD8(+) (P = 0.042) and CD19(+) cells (P = 0.044) were significantly associated with the absolute lymphocyte count (ALC) at engraftment. The dose of infused CD34(+) cells was not associated with the change of lymphocyte subsets except for an inverse correlation with CD4(+) cells (P = 0.006). After adjusting for potential variables in univariate analysis, multivariate analyzes revealed that the lower ratio of infused CD4(+) to CD8(+) cells (P = 0.030) was an independent factor for severe mucositis. Of lymphocyte subsets at engraftment, a higher frequency of CD3(+) (P = 0.024) and a lower frequency of CD56(+) (P = 0.020) were independent predictors for infections after engraftment. A higher frequency of CD8(+) cells (P = 0.041) and a lower ratio of CD4(+) to CD8(+) (P = 0.021) were independent predictors for CMV reactivation. CONCLUSIONS: Our data suggest that lymphocyte subset analysis of infused autograft and peripheral blood at engraftment may provide new predictors for early complications after ASCT in patient with MM. PMID- 22309318 TI - Chronic cocaine exposure during pregnancy increases postpartum neuroendocrine stress responses. AB - The cycle of chronic cocaine (CC) use and withdrawal results in increased anxiety, depression and disrupted stress-responsiveness. Oxytocin and corticosterone (CORT) interact to mediate hormonal stress responses and can be altered by cocaine use. These neuroendocrine signals play important regulatory roles in a variety of social behaviours, specifically during the postpartum period, and are sensitive to disruption by CC exposure in both clinical settings and preclinical models. To determine whether CC exposure during pregnancy affected behavioural and hormonal stress response in the early postpartum period in a rodent model, Sprague-Dawley rats were administered cocaine daily (30 mg/kg) throughout gestation (days 1-20). Open field test (OFT) and forced swim test (FST) behaviours were measured on postpartum day 5. Plasma CORT concentrations were measured before and after testing throughout the test day, whereas plasma and brain oxytocin concentrations were measured post-testing only. The results obtained indicated increased CORT response after the OFT in CC-treated dams (P <= 0.05). CC-treated dams also exhibited altered FST behaviour (P <= 0.05), suggesting abnormal stress responsiveness. Peripheral, but not central, oxytocin levels were increased by cocaine treatment (P <= 0.05). Peripheral oxytocin and CORT increased after the FST, regardless of treatment condition (P <= 0.05). Changes in stress-responsiveness, both behaviourally and hormonally, may underlie some deficits in maternal behaviour; thus, a clearer understanding of the effect of CC on the stress response system may potentially lead to treatment interventions that could be relevant to clinical populations. Additionally, these results indicate that CC treatment can have long-lasting effects on peripheral oxytocin regulation in rats, similar to changes observed in persistent social behaviour and stress-response deficits in clinical populations. PMID- 22309320 TI - Repair of thoracic aortic aneurysm due to noninfectious aortitis. AB - BACKGROUND AND AIM: Isolated thoracic aortitis (ITA) is a newly-defined pathological entity with a still-unknown etiopathology and with some potential relationship to IgG4-related systemic disease. We investigated patients on whom the ascending aorta was operated to identify the clinical and histopathological features of ITA and its relationship to IgG4-related systemic disease. METHODS: Two hundred fifty-one patients underwent replacement of the ascending aorta. Retrospective review of all histological reports was done to identify noninfectious aortitis. Immunohistochemical analysis of resected specimens was performed in all cases. RESULTS: We found 11 (4.4%) patients with noninfectious aortitis aged 52 to 79 years; nine of the patients were female. All patients underwent ascending aorta replacement. The 30-day mortality was 0. During the follow-up period (median 12 months) four patients died (two of them because of progression of aortic disease). None of the seven living patients developed any IgG4-related diseases, and all had normal serum levels of IgG and IgG4. CONCLUSIONS: Surgical treatment of ITA has acceptable short- and mid-term results. Because follow-up serum levels of IgG and IgG4 were normal in survivors, postoperative corticosteroid therapy may not be indicated in patients in the absence of active vasculitis. PMID- 22309321 TI - Enhanced recovery after laparoscopic colorectal resection with primary anastomosis: accelerated discharge is safe and does not give rise to increased readmission rates. AB - AIMS: Enhanced recovery programmes after colorectal surgery are promoted to minimize complications and expedite recovery, thus reducing length of hospital stay where appropriate and improving the overall standard of patient care. There are few published trials of enhanced recovery programmes in the context of laparoscopic colorectal surgery. METHODS: Data were prospectively collected on all laparoscopic colorectal resections carried out in our institution from May 2004 to November 2009. An informal move to 48-h discharge was introduced in May 2004 and the official enhanced recovery programme was launched in November 2008. We identified all patients with a primary anastomosis discharged within 3 days of surgery. Early outcomes - leaks, complications, readmission rates and returns to theatre - were analysed. RESULTS: In all, 606 resections were performed in this period. Median length of stay was 4 (0-52) days. Of these patients, 279 (46%) met the criteria of accelerated discharge by day 3: 2 (0.7%) were discharged on the day of surgery, 70 (25.1%) within 24 h, 116 (41.6%) within 48 h and 91 (32.6%) by 72h. Age was not a significant factor in determining length of stay. Patients undergoing right hemicolectomy were more likely to be discharged by 24 h than those with left-sided anastomoses, and patients having total mesorectal excision resections were more likely to stay 3 days. The readmission rate was 4%, regardless of day of discharge. CONCLUSION: Accelerated discharge is feasible and safe. High readmission rates reported in enhanced recovery programmes after open colorectal surgery have not occurred in our laparoscopic experience. PMID- 22309322 TI - Absence of central nervous system and hypothermic effects after single oral administration of high doses of oseltamivir in the rat. AB - Oseltamivir is widely used for the treatment and prophylaxis of influenza. Renewed interest in the central nervous system (CNS) tolerability profile of oseltamivir has been triggered by the reports of neuropsychiatric adverse events in patients with influenza. In addition, a recent pre-clinical study in rodents suggested a hypothermic effect of oseltamivir. The current studies investigated the CNS effects, body temperature effect and toxicokinetic profile of oseltamivir in rats. The CNS/temperature study included three groups receiving oseltamivir (500, 763 and 1000 mg/kg free base by oral gavage), one vehicle/control group and one reference group (D-amphetamine, 10 mg/kg). CNS parameters (behaviour, motor activity and co-ordination and sensory/motor reflex responses) and rectal temperature were measured at baseline and at five intervals until 8 hr after dosing. In the toxicokinetic study, rats received oseltamivir by oral gavage at 763 or 1000 mg/kg free base. Plasma, cerebrospinal fluid (CSF) and perfused brain concentrations of oseltamivir and its active metabolite, oseltamivir carboxylate (OC), were measured until 8 hr after dosing. Median scores for CNS parameters were similar in controls and animals receiving oseltamivir at all time points. Oseltamivir had no physiologically relevant effect on body temperature, but induced a short-lived and small dose-independent decrease in temperature in all active treatment groups at 1 hr after dosing only. Plasma concentrations of OC were higher than of oseltamivir, but the reverse was true in CSF and brain. CNS penetration was low for both moieties. In rats, oseltamivir at supratherapeutic doses up to 1000 mg/kg free base did not exert any effects on CNS function or hypothermic effects and led to limited CNS exposure, resulting in large safety margins. PMID- 22309323 TI - Immunohistochemical study of the muscularis externa of the esophagus in achalasia patients. AB - The etiology of achalasia is believed to be the neuropathy associated with chronic inflammation of the nerve plexus, but the cause of plexus inflammation is unknown. The purpose of this study was to evaluate the pathophysiology of achalasia by examining the muscularis externa of the esophagus. We used the muscularis externa of the esophagus of 62 patients with achalasia (median 44 years, male : female 32:30) who underwent surgical treatment (achalasia group) and of 10 patients (median 65.5 years, male : female 9:1) who underwent esophagectomy for thoracic esophageal cancer (control group) to perform immunohistochemical staining with S-100, CD43, c-kit (CD117), n-NOS, vasoactive intestinal polypeptide (VIP), and ubiquitin. The cell counts that were positive for S-100, n-NOS, VIP, and ubiquitin were significantly lower in the achalasia group compared with the control group (P < 0.001, P= 0.001, P < 0.001, and P= 0.001, respectively). There were no statistically significant differences with respect to CD43 and c-kit staining (P= 0.586 and P= 0.209, respectively). In conclusion, the pathophysiology of achalasia is therefore considered to be an impaired production of NO and VIP, which both affect interstitial cell of Cajal and smooth muscles, and this impairment is therefore considered to play a role in the pathophysiology of achalasia. PMID- 22309324 TI - The use of methotrexate in dermatology: a review. AB - Methotrexate is a synthetic folic acid analogue valued for both its anti proliferative and anti-inflammatory properties. Considered one of the original immune-modifying agents, it is used widely for the treatment of steroid recalcitrant inflammatory diseases. While there are abundant studies documenting its efficacy in rheumatic diseases, the use of methotrexate for dermatological conditions, with the exception of psoriasis, has yet to be comprehensively explored. This two-part review firstly outlines current data concerning the pharmacology of methotrexate, including its mechanism of action, side-effect profile and recommended therapeutic approach, and, secondly, examines the emerging evidence for methotrexate's efficacy in a wide range of cutaneous disorders. PMID- 22309325 TI - Effect of early and late mobilisation on split skin graft outcome. AB - BACKGROUND: There is an increasing trend towards early mobilisation post-split skin grafting of the lower limbs. This study was performed to determine if early mobilisation impacts negatively on graft healing and patient morbidity. METHODS: A retrospective review of 48 cases of lower limb split skin grafts performed by the plastic surgery department at Royal Perth Hospital was undertaken. Patients were stratified into early and late mobilisation groups. RESULTS: No difference in outcome was identified with early mobilisation, but an increased rate of deconditioning with increased length of stay was present with late mobilisation. CONCLUSION: These results suggest that early mobilisation post-split skin grafting of the lower limb is beneficial to patient care and is associated with lower morbidity. PMID- 22309326 TI - Better, sooner, more convenient: a successful teledermoscopy service. AB - BACKGROUND/OBJECTIVES: A virtual lesion clinic (VLC) using store-and-forward teledermoscopy was introduced to reduce waiting times and improve access for skin lesion assessment by dermatologists. We aimed to review the efficiency and patient acceptance of a new community-based teledermoscopy service by comparing it to hospital-based face-to-face (FTF) skin lesion clinics. METHODS: A prospective study compared patient flow through a community-based VLC and a tertiary hospital FTF dermatology clinic. Surveys were sent to patients and their referring doctors after attendance. Waiting times, diagnosis, outcomes, financial costs, patient acceptability and convenience were compared. RESULTS: A total of 300 patients were assessed; 200 were seen in the VLC and 100 in the conventional FTF clinic. Of the 200 patients seen in the VLC, 88% did not require a subsequent FTF clinic assessment to establish the diagnosis. Mean waiting times for first assessment were reduced by two thirds (from 114 days to 39 days) in those seen by the VLC compared to FTF. Financial analysis demonstrated cost savings of 14%. Surveyed patients were highly satisfied and confident in the VLC service. CONCLUSIONS: A community-based teledermoscopy service may allow improved management of outpatient referrals while providing a better, quicker and more convenient service. It may also provide cost savings, as teledermoscopy assessment can be cheaper than traditional assessment. PMID- 22309327 TI - Sentinel lymph node biopsy in patients with Merkel cell carcinoma: an emerging role and the Westmead hospital experience. AB - BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy which has a high rate of nodal metastasis. Sentinel lymph node biopsy (SLNB) enables the identification of occult nodal metastases. We sought to calculate the rates of positive and false negative SLNB and to evaluate the impact of SLNB on the staging and management of patients with MCC at our institution. METHODS: A total of 16 patients with stage I or II MCC who had undergone SLNB were identified from a prospectively maintained database of 114 patients with MCC who presented to Westmead Hospital, Sydney, Australia between 2000 and 2010. Data on patient characteristics, tumour and treatment details and patient follow up were extracted from a computer database and patient medical records. RESULTS: Eight patients (50%) had a positive SLNB and eight had a negative SLNB. The median follow up from diagnosis was 19.5 months (range 4-40) with most patients (69%) alive without evidence of disease at the time of last follow up. All eight patients with a positive SLNB subsequently underwent nodal treatment. This consisted of radiotherapy in five and completion lymphadenectomy and adjuvant radiotherapy in three. None of the eight patients who had a negative SLNB underwent any nodal treatment following SLNB. Two of these patients developed nodal relapse, giving a false negative rate of 20%. CONCLUSION: Half of our patients were upstaged and underwent nodal treatment as a result of their SLNB. Given the high rate of SLNB positivity, we believe that SLNB has a role in the management of MCC. As there is a risk of a false negative SLNB, close observation of the regional nodal basins is warranted in patients who have had a negative SLNB. Further studies are required to investigate the impact of SLNB on survival. PMID- 22309328 TI - A single centre melanoma thickness trend (1985-2009) in relation to skin areas accessible and non-accessible to self-inspection. AB - BACKGROUND/OBJECTIVES: Melanoma has become a major public health problem worldwide and its incidence in individuals of Caucasian origin continues to rise. The objective was to determine historical changes in thickness, melanoma proportions and anatomical site of presentation over a 25-year period in our Department. METHODS: This was a historical retrospective study (January 1985 to December 2009). Only patients born and living in Italy were considered. The following parameters were evaluated: age, gender, year of diagnosis, site of primitive lesion (head, back, chest, anterior and posterior upper limbs, anterior and posterior lower limb, and acral sites) and Breslow thickness of the lesion. RESULTS: In the 25-year period, 993 cases of melanoma were diagnosed. The total number of cases per year tripled between 1985-1989 and 1995-1999 and more than doubled between 1995-1999 and 2005-2009. Our results also revealed that thicker melanomas were more frequent in elderly patients and on parts of the body that cannot be readily self-inspected. CONCLUSION: The importance of observation of the posterior parts of the body is stressed, since not only did most melanomas arise in these sites but the diagnosis of lesions in these sites is often delayed. PMID- 22309329 TI - Determinants of the direction of hair follicle growth after reconstruction with dissociated cells. AB - BACKGROUND/OBJECTIVES: Several hair follicle reconstruction models based on the implantation of dissociated cells have been established. However, little has been said about the direction of growth, which is a very important issue for clinical applications. The aim of this study was to reveal the factors that determine the direction of hair follicle growth after reconstruction with dissociated cells. METHODS: We designed an enclosed chamber assay in which a chamber was buried under nude mouse skin that was not exposed to the air, as in a traditional chamber assay. Inductive dermal cells and epithelial cells dissociated from neonatal C57 BL/6 mice were injected into the chamber and dermis for patch assays. The direction of newly formed hair follicles was analysed. RESULTS: Newly formed hair follicles in the enclosed chamber were arranged randomly parallel to the skin on the surface of the panniculus carnosus. CONCLUSIONS: These results indicate that developmental space provides the possibility for growth of reconstructed hair follicles and that the air-liquid interface determines the final direction of growth. PMID- 22309330 TI - Pilot study on the acceptance of mobile teledermatology for the home monitoring of high-need patients with psoriasis. AB - BACKGROUND/OBJECTIVES: The willingness to be educated is one of the highest desires among patients with psoriasis. Therefore, a collaborative model of management would appear to be essential in enhancing patient satisfaction in this challenging condition. The present study aimed at examining the applicability of a mobile teledermatology service in this regard and assessing the association between patient acceptance and perceived health-related quality of life. METHODS: High-need patients with psoriasis performed visits over 12 weeks transmitting clinical images together with some relevant clinical information via mobile phones to teledermatologists, who provided treatment instructions. Ten patients and two teledermatologists completed 20-item patient (weeks 6 and 12) and 10-item physician (at week 12) acceptance questionnaires. In addition, patients answered the dermatology life quality index (DLQI) at weeks 0, 6 and 12. RESULTS: Both patients and teledermatologists were pleased with the service with high acceptance rates (patients: 81.0% at week 6 and 82.9% at week 12; teledermatologists: 74.0%). In addition, 80% of the patients considered the service an alternative to in-person consultation and 90% felt they were in good hands but had achieved a more flexible and empowered lifestyle. No significant correlations were found between patient acceptance and DLQI. Both teledermatologists found the service a convenient and reliable tool for patient monitoring. Neither patients nor teledermatologists thought further in-person consultations necessary. CONCLUSION: Mobile teledermatology is a valuable tool for the home monitoring of patients with psoriasis that makes a meaningful difference in their lives. It is well accepted by both patients and the physicians involved. PMID- 22309331 TI - Dermoscopy of acquired digital fibrokeratoma. PMID- 22309332 TI - Hybrid cysts: a clinicopathological study of seven cases. AB - Hybrid cysts develop from more than two components of the pilosebaceous unit. The pathogenesis of this unusual disease has not yet been elucidated. The aim of this study was to assess the clinical and histopathological features of hybrid cysts. Histological sections of seven cases indexed as hybrid cysts were reviewed from 1996-2009 at the Department of Dermatology, Eulji Medical Center, Seoul, Korea. Hospital charts and slides were retrospectively evaluated. All cases had a combination of an epidermal cyst and a pilomatricoma with sharp transitional zones. The epidermal cyst lining was composed of thickened stratified squamous epithelium with a granular layer. Basophilic cells, shadow cells and the contents of the pilomatricoma were present in all lesions. There were no differences in the clinical features between patients with hybrid cysts and others with single cystic lesions. There were five women and two men, ranging in age from 11 to 50 years (mean 27 years). The most common sites were the upper extremities. None of the patients had any sign of Gardner's syndrome. Hybrid cysts are an interesting pathological phenomenon. Further study is needed to analyze hybrid cysts to improve our understanding of their pathogenesis and development from tumours of the pilosebaceous unit. PMID- 22309333 TI - Topical 0.1% rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: a pilot study of four patients. AB - Tuberous sclerosis complex (TSC) is an autosomal dominant genodermatosis characterised by the development of hamartomatous tumours in multiple organs including the brain, skin, kidneys, heart and lungs. Facial angiofibromas are the most visible and unsightly of the cutaneous manifestations of TSC, often resulting in stigmatisation for both the affected individuals and their families. Current treatments include vascular laser, ablative lasers and other destructive techniques such as shave excision and electrodessication. For the best outcome these treatments have to be repeated throughout childhood and teenage years, necessitating multiple general anaesthetics. We report a pilot study of topical rapamycin in four children with TSC and facial angiofibromas. Two patients were trialled on 0.1% rapamycin in petrolatum and the other two patients with 0.1% rapamycin solution (Rapamune) applied topically. Both preparations were rapidly and equally effective, however the 0.1% in petrolatum was much better tolerated. Younger patients with smaller angiofibromas had the best response with near complete clearance. Both preparations were more cost effective than pulsed dye laser under general anaesthesia. Although larger studies are needed, this treatment shows a potential to be a first-line management for facial angiofibromas in TSC and appears safe to start in early childhood. PMID- 22309334 TI - The rapid onset of multiple squamous cell carcinomas in two patients commenced on ustekinumab as treatment of psoriasis. AB - We report the cases of two patients who developed eruptive cutaneous squamous cell carcinomas (SCC) soon after commencement of ustekinumab, as treatment of moderate to severe plaque type psoriasis. Ustekinumab is a human monoclonal antibody with a novel mechanism, selectively targeting the shared p40 subunit of interleukin-12 (IL-12) and IL-23. Its efficacy has been well documented in three large phase-III trials (PHOENIX I, PHEONIX 2, ACCEPT). Safety data on this new biological agent continue to grow. To date, no link between ustekinumab and cutaneous carcinogenesis has been demonstrated and, to our knowledge, these cases are the first of their kind. Importantly, both these patients had independent risk factors for developing non-melanoma skin cancers; however, the specific time correlation with the administration of ustekinumab is of note. Our report suggests that ustekinumab may allow the development of cutaneous carcinomata in predisposed individuals. PMID- 22309335 TI - Ectodermal dysplasia-skin fragility syndrome due to a new homozygous internal deletion mutation in the PKP1 gene. AB - Ectodermal dysplasia-skin fragility syndrome (ED-SFS) is a rare autosomal recessive genodermatosis resulting from mutations in the PKP1 gene, encoding the desmosomal plaque protein plakophilin-1 (PKP1). Mutations in PKP1 may manifest with skin fragility and erosions, patches of scale crust on the trunk and limbs, peri-oral cracking and inflammation, hypotrichosis, palmoplantar keratoderma with painful fissuring and other somewhat variable ectodermal anomalies. Ten cases of the syndrome have been reported. We report a further case of this desmosomal genodermatosis. A 14-month old child, born to consanguineous parents, presented with a history of neonatal bullae and subsequent development of dystrophic nails, sparse eyelashes and eyebrows, woolly scalp hair, abnormal dental development and a desquamating erythematous rash at sites of trauma. A clinical diagnosis of ED SFS was supported by skin biopsy findings of suprabasal intraepidermal clefting and a loss of immunoreactivity for PKP1. Sequencing of genomic DNA revealed a homozygous 5 base pair deletion in exon 5 of the PKP1 gene, designated c.897del5 (CAACC). This new mutation creates a frameshift, leading to a downstream premature termination codon, p.Pro299fsX61. This case highlights the clinicopathological consequences of inherited mutations in the PKP1 gene and illustrates the key role of desmosomes in skin biology. PMID- 22309336 TI - Successful treatment of a severe persistent case of pemphigoid gestationis with antepartum and postpartum intravenous immunoglobulin followed by azathioprine. AB - We report a case of pemphigoid gestationis affecting a 37-year-old woman in both her pregnancies. In her second pregnancy she failed to respond to high-dose oral prednisolone. She was treated successfully with intravenous immunoglobulin (2 g/kg each infusion cycle) as a steroid-sparing agent during both the antepartum and postpartum period. The baby was born at the 36th week of gestation. No complications were noted for either mother or baby. After ceasing intravenous immunoglobulin, azathioprine (up to a dose of 1 mg/kg/day) was used to adequately control her pemphigoid gestationis. PMID- 22309337 TI - Psoriasiform eruption triggered by a dipeptidyl peptidase IV inhibitor. AB - Psoriatic patients have a higher prevalence of diabetes mellitus type 2 (DM). Since dipeptidyl peptidase IV (DPP-IV) dysregulation is present in DM and psoriasis, DPP-IV inhibitors have been proposed as therapeutic agents for both conditions. We report a psoriasiform eruption induced by sitagliptin, a DPP-IV inhibitor. The role of DPP-IV in the pathogenesis of DM is well established; however data on psoriatic patients is contradictory. More studies are required to elucidate the effect of DPP-IV inhibitors and their relationship with DM and psoriasis. PMID- 22309338 TI - Changing the way we diagnose tuberculids with interferon gamma release assays. AB - Diagnosing tuberculids traditionally requires clinicopathological correlation together with positive tuberculin skin tests (TST) or demonstration of Mycobacterium tuberculosis (MTB) DNA by polymerase chain reaction (PCR). Interferon gamma release assays (IGRA) are new laboratory tests approved for the diagnosis of MTB infection. We describe three patients with tuberculids who had no other clinical feature of tuberculosis (TB) infection and negative PCR of skin biopsies. Their diagnoses were aided by positive IGRA. PMID- 22309339 TI - Allergic contact dermatitis caused by a cell phone cover. AB - We describe a case of contact dermatitis to a phone cover, which was compounded by secondary allergic contact dermatitis to topical creams used. The phone cover was advertised as being composed of silicone only. Patch testing with the cover material confirmed the diagnosis. In addition, there were positive patch test reactions to a number of allergens in the plastics and glues series from Chemotechnique Diagnostics (Malmo, Sweden). The increasing use of phone covers and the multiple positive reactions to chemicals used in plastic manufacture seen in this case suggest that similar allergic reactions may occur more frequently in the future and should be considered in the differential diagnosis of facial dermatitis. PMID- 22309340 TI - A case of erythema elevatum diutinum associated with peripheral ulcerative keratitis. AB - A young woman with recurrent painful lesions on the dorsal aspects of her hands associated with arthralgia presented with pain and redness of both eyes. After extensive investigations, a diagnosis of erythema elevatum diutinum accompanied by peripheral ulcerative keratitis was made. The patient was treated with dapsone 50 mg, t.i.d., and responded well. PMID- 22309341 TI - Methotrexate toxicity presenting as ulcerated psoriatic plaques. AB - Methotrexate toxicity is known to cause erosions of existing psoriatic plaques, although rare. We describe two patients who developed painful ulcerated psoriatic plaques as an early presenting sign of methotrexate toxicity and review the risk factors associated with this manifestation. PMID- 22309343 TI - Treatment-resistant elephantiasic thyroid dermopathy responding to rituximab and plasmapheresis. AB - A 44-year-old woman was diagnosed with Graves' disease in 1995 and over the following 12 months developed thyroid dermopathy (pretibial myxoedema). Despite being trialled on multiple recognized therapies over the course of 11 years, the patient's dermopathy progressively worsened. She developed ocular proptosis, elephantiasic thyroid dermopathy and acropachy in both hands. In mid 2006, the patient was started on rituximab and plasmapheresis, with rapid response. The patient's condition stabilized and in October 2009 at the age of 58 years she was able to cease therapy. PMID- 22309344 TI - Childhood actinic lichen planus: successful treatment with antimalarials. AB - Actinic lichen planus (ALP) is a photosensitive variant of lichen planus, affecting mainly young adults of Middle Eastern descent. We report a case of ALP in a 9-year-old Colombian girl with an excellent response to hydroxychloroquine and photoprotection. PMID- 22309345 TI - Tinea nigra and dermoscopy. PMID- 22309347 TI - Recurrent distal digital keratoacanthoma of the periungual region treated with Mohs micrographic surgery. AB - We report a 42-year-old man who presented with a recurrent painful nodule on the proximal nail fold of the left fifth finger. The tumour had been surgically excised at another department a month earlier, and histological examination had shown a keratoacanthoma. The patient underwent Mohs micrographic surgery, and no recurrence was evident 16 months later. Mohs micrographic surgery appears to be an effective option in the management of this unusual variant of keratoacanthoma, which is often difficult to eradicate. PMID- 22309348 TI - Folliculosebaceous cystic hamartoma of the ear and periauricular skin. AB - Folliculosebaceous cystic hamartoma (FSCH) is a rare, recently recognized cutaneous hamartoma comprised of follicular, sebaceous and mesenchymal elements. Fewer than 30 cases have been reported to date. The authors present two additional cases of FSCH. PMID- 22309349 TI - Histochemical and morphometric analyses of the musculature of the forelimb of the subterranean rodent Ctenomys talarum (Octodontoidea). AB - Histochemical and morphometric analyses were performed to characterize the fibre type composition of two forelimb muscles of the South American subterranean rodent Ctenomys talarum. The studied muscles were the triceps lateralis, an extensor of the elbow, and the teres major, a flexor of the shoulder. It was found that these muscles had an elevated proportion of fast oxidative-glycolytic (FOG) fibres, and lower proportions of slow oxidative (SO) and fast glycolytic (FG) fibres. This composition probably qualifies the teres major and triceps muscles to perform the sustained effort required in tunnelling excavation. The results were discussed considering published data on fibre-type composition of mammals having different modes of life and digging behaviour. We here suggest that C. talarum has the potential of generating forces linked to rapid, powerful movements during sustained periods by means of an elevated proportion of FOG fibres, together with osteological changes that result in a great mechanical advantage of the forelimb muscles. PMID- 22309350 TI - Older people's perception of their readiness for discharge and postdischarge use of community support and services. AB - AIM: To examine older patients perception of their readiness for discharge from hospital to home and use of community supports postdischarge, including readmission. BACKGROUND: Early discharge leaves little time for older people, families and professionals to prepare. The perspectives of patients are essential to therapeutic caring; however, few studies have examined patient's perception of their readiness for discharge. DESIGN: A quantitative, descriptive and correlational design was used. Data were collected from older patients (n = 335) at discharge and postdischarge using the Readiness for Discharge Scale (Weiss & Piacentine; Journal of Nursing Measurement, 14, 2006, 163) and a Demographic and Community Resource Questionnaire. FINDINGS: At 6 weeks postdischarge, almost one quarter had been readmitted. Family support had increased, yet a minimal increase in formal services was found. At discharge, differences in readiness existed between the younger and older old. Significant relationships existed between lower perception of readiness at discharge and increased use of informal and formal support post-discharge. Lower perception of readiness had a significant relationship with readmission in the older old. CONCLUSIONS: Perceptions of readiness reflect the patient's reality and may be significant to discharge preparation and arrangements for support. IMPLICATIONS FOR PRACTICE: Older patients' perspectives should be included in discharge decisions and in individualised approaches by nurses to discharge preparation. PMID- 22309352 TI - Red leaf margins indicate increased polygodial content and function as visual signals to reduce herbivory in Pseudowintera colorata. AB - Red-pigmented leaf margins are common, but their functional significance is unknown. We hypothesized that red leaf margins reduce leaf herbivory by signalling to herbivorous insects the presence of increased chemical defences. Leaves were collected from a natural population of Pseudowintera colorata. Margin size, herbivory damage, anthocyanin content and concentrations of polygodial, a sesquiterpene dialdehyde with antifeedant properties, were quantified. Feeding trials involving larvae of Ctenopseustis obliquana, a generalist herbivore, were conducted on red- and green-margined P. colorata leaves in darkness, or under white, green or red light. Leaves with wider red margins contained higher concentrations of polygodial and anthocyanins, and incurred less natural herbivory. In trials under white light, C. obliquana consumed disproportionately more green- than red-margined leaf laminae. Larvae exhibited no feeding preference when light was manipulated such that leaf colour discrimination was impaired. Red leaf margins provide a reliable and effective visual signal of chemical defence in P. colorata. Ctenopseustis obliquana larvae perceive and respond to the colour of the leaf margins, rather than to olfactory signals. Our study provides direct experimental evidence for aposematic coloration in red leaves. PMID- 22309353 TI - Antimicrobial activity of lauric arginate-coated polylactic acid films against Listeria monocytogenes and Salmonella typhimurium on cooked sliced ham. AB - A novel type of environmentally friendly packaging with antibacterial activity was developed from lauric arginate (LAE)-coating of polylactic acid (PLA) films after surface activation using a corona discharge. Scanning electron microscopy (SEM)-based analysis of the LAE/PLA films confirmed the successful coating of LAE on the PLA surface. The mechanical properties of the LAE/PLA films with different levels of LAE-coating (0% to 2.6%[w/w]) were essentially the same as those of the neat PLA film. The antibacterial activity of the LAE/PLA films against Listeria monocytogenes and Salmonella enterica Serovar Typhimurium (S. Typhimurium) was confirmed by a qualitative modified agar diffusion assay and quantitative JIS Z 2801:2000 method. Using the LAE/PLA film as a food-contact antimicrobial packaging for cooked cured ham, as a model system, suggested a potential application to inhibit L. monocytogenes and S. Typhimurium on ham with a 0.07% (w/w) LAE coating on the PLA when high transparency is required, as evidenced from the 2 to 3 log CFU/tested film lower pathogen growth after 7 d storage but even greater antibacterial activity is obtained with a LAE coating level of 2.6% (w/w) but at the cost of a reduced transparency of the finished product. This article shows how we can simply develop functional green packaging of PLA for food with effective and efficient antimicrobial activity by use of LAE coating on the surface via corona discharge. PRACTICAL APPLICATION: The effectiveness of an innovative antimicrobial LAE-coated PLA film against foodborne pathogens was demonstrated. Importantly, the application of the LAE to form the LAE-coated PLA film can be customized within current film manufacturing lines. PMID- 22309354 TI - Optimizing pacemaker longevity with pacing mode and settings programming: results from a pacemaker multicenter registry. AB - BACKGROUND: This study aimed to describe the influence on dual-chamber devices' expected longevity of devices' settings. METHODS: Data from patients implanted with dual chamber devices (SymphonyTM, SORIN CRM SAS, Clamart, France) from 2003 to 2006 were collected in registries. Programmer files were retrieved: device estimated longevity, assessed through algorithm prediction, was analyzed according to device settings. RESULTS: One thousand sixty-eight recipients of dual chamber pacemaker in sinus rhythm (75.3+/-11.1 years, 54.5% male, ventricular block 30%, brady-tachy syndrome 21%, and sinus node dysfunction 49%) were followed up to 14.2+/-12.1 months (ranging from first quartile Q1: 2.9 months to fourth quartile Q4: 49.3 months) after implantation. DDD with automatic mode conversion and minimized ventricular pacing (SafeR) modes were programmed in 34.3%, 2.9%, and 62.8% of the patients, respectively. The mean total longevity estimated by the device was 134.1+/-31.5 months (11.2+/-2.6 years). Significant increase in longevity was observed in devices undergoing at least one reprogramming (134.4+/-31.4 months) versus device presenting no reprogramming (103.4+/-32.3 months, P=0.0005). The parameters associated with the major increase in mean longevity were the mode (mean longevity increase of +23.9 months in SafeR as compared to DDD mode, P<0.0001) and the atrial (A) and ventricular (V) amplitudes (mean longevity increase of +29.6 and +26.9 months for a decrease of less than 1V in A and V outputs respectively, P<0.0001). CONCLUSION: This study provides information on dual chamber pacemakers' longevity and highlights the impact of devices' reprogramming on expected longevities. PMID- 22309355 TI - Loading dose required to achieve rapid therapeutic teicoplanin trough plasma concentration in patients with multidrug-resistant gram-positive infections. AB - Teicoplanin is an antibiotic drug prescribed for the treatment of multidrug resistant Gram-positive infections. However, there is currently no consensus as to the optimal teicoplanin loading dose. The objective of this study was to compare plasma concentrations of teicoplanin in patients with multidrug-resistant Gram-positive infections after the administration of two different loading doses. Two groups of patients were infused intravenously with four loading doses of 6 mg/kg body-weight (group A, n = 12) or 12 mg/kg body-weight (group B, n = 11). The first three loading doses were administered at 12-hr intervals, and the fourth was given 24 hr after the third dose. Maintenance doses of 6 mg/kg were administered every day, every other day or every third day depending on the individual's creatinine clearance, and teicoplanin trough plasma concentrations were monitored. Only samples obtained on the same day for both groups were compared statistically. A higher percentage of group B patients achieved the desired therapeutic concentration of teicoplanin (C(min.) >= 10 mg/L) on days 2 and 3 (90.0% and 100%, respectively) compared with patients in group A (18.2% and 16.7%, respectively) (p < 0.001). In addition, more patients in group B achieved therapeutic concentrations from days 2 through 12. In conclusion, despite limitations in drawing definitive conclusions because of a relatively small sample size and variability in renal impairment among patients, our findings suggest that a teicoplanin loading dose of 12 mg/kg body-weight results in a safe and rapid attainment of therapeutic trough plasma concentrations. This regimen may enhance treatment efficacy. PMID- 22309356 TI - Radiographic knee osteoarthritis in ex-elite table tennis players. AB - BACKGROUND: Table tennis involves adoption of the semi-flexed knee and asymmetrical torsional trunk movements creating rotational torques on the knee joint which may predispose players to osteoarthritis (OA) of the knee. This study aims to compare radiographic signs of knee OA and associated functional levels in ex-elite male table tennis players and control subjects. METHODS: Study participants were 22 ex-elite male table tennis players (mean age 56.64 +/- 5.17 years) with 10 years of involvement at the professional level and 22 non-athletic males (mean age 55.63 +/- 4.08 years) recruited from the general population. A set of three radiographs taken from each knee were evaluated by an experienced radiologist using the Kellgren and Lawrence (KL) scale (0-4) to determine radiographic levels of OA severity. The intercondylar distance was taken as a measure of lower limb angulation. Participants also completed the pain, stiffness, and physical function categories of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) 3.1 questionnaire. RESULTS: The results showed 78.3% of the ex-elite table tennis players and 36.3% of controls had varying signs of radiographic knee OA with a significant difference in the prevalence levels of definite radiographic OA (KL scale > 2) found between the two groups (P <= 0.001). Based on the WOMAC scores, 68.2% of the ex-elite table tennis players reported symptoms of knee pain compared with 27.3% of the controls (p = 0.02) though no significant differences were identified in the mean physical function or stiffness scores between the two groups. In terms of knee alignment, 73.7% of the ex-elite athletes and 32% of the control group had signs of altered lower limb alignment (genu varum) (p = 0.01). Statistical differences were found in subjects categorized as having radiographic signs of OA and altered lower limb alignment (p = 0.03). CONCLUSIONS: Ex-elite table tennis players were found to have increased levels of radiological signs of OA in the knee joint though this did not transpire through to altered levels of physical disability or knee stiffness in these players when compared with subjects from the general population suggesting that function in these players is not severely impacted upon. PMID- 22309357 TI - Influence of the DSM-IV Outline for Cultural Formulation on multidisciplinary case conferences in mental health. AB - The Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association (DSM-IV-TR) includes an Outline for Cultural Formulation (CF) that identifies cultural information that can be used to modify diagnosis, clinical assessment and treatment plan. This study examined the use of the CF by a Cultural Consultation Service in the psychiatric assessment of patients referred by primary care providers. The study uses conversation analysis of 12 clinical case conferences to explore the ways in which the CF influenced the interaction of a multidisciplinary group of mental health professionals in conceptualizing the implications of patients' cultural background and current context for diagnosis and treatment planning. The results suggest that the CF can be a useful tool for interdisciplinary collaboration and knowledge transfer by providing a framework to systematically introduce different disciplinary perspectives and levels of description that transcend the narrow frame of disorder-centred psychiatric diagnosis, assessment and care. PMID- 22309358 TI - The establishment of a bank of stored clinical bone marrow stromal cell products. AB - BACKGROUND: Bone marrow stromal cells (BMSCs) are being used to treat a variety of conditions. For many applications a supply of cryopreserved products that can be used for acute therapy is needed. The establishment of a bank of BMSC products from healthy third party donors is described. METHODS: The recruitment of healthy subjects willing to donate marrow for BMSC production and the Good Manufacturing Practices (GMP) used for assessing potential donors, collecting marrow, culturing BMSCs and BMSC cryopreservation are described. RESULTS: Seventeen subjects were enrolled in our marrow collection protocol for BMSC production. Six of the 17 subjects were found to be ineligible during the donor screening process and one became ill and their donation was cancelled. Approximately 12 ml of marrow was aspirated from one posterior iliac crest of 10 donors; one donor donated twice. The BMSCs were initially cultured in T-75 flasks and then expanded for three passages in multilayer cell factories. The final BMSC product was packaged into units of 100 * 106 viable cells, cryopreserved and stored in a vapor phase liquid nitrogen tank under continuous monitoring. BMSC products meeting all lot release criteria were obtained from 8 of the 11 marrow collections. The rate of growth of the primary cultures was similar for all products except those generated from the two oldest donors. One lot did not meet the criteria for final release; its CD34 antigen expression was greater than the cut off set at 5%. The mean number of BMSC units obtained from each donor was 17 and ranged from 3 to 40. CONCLUSIONS: The production of large numbers of BMSCs from bone marrow aspirates of healthy donors is feasible, but is limited by the high number of donors that did not meet eligibility criteria and products that did not meet lot release criteria. PMID- 22309359 TI - Primary cardiac chondrosarcoma. AB - Primary cardiac chondrosarcoma is extremely rare, and its clinical characteristics and management are not clear. Only eight cases of primary cardiac chondrosarcoma in the left heart have been reported in the English literature. In this report, we describe a case of primary chondrosarcoma of the left atrium. The management of these rare tumors is the subject of this report. PMID- 22309360 TI - A light-responsive reversible molecule-gated system using thymine-modified mesoporous silica nanoparticles. AB - In this paper, a reversible light-responsive molecule-gated system based on mesoporous silica nanoparticles (MSN) functionalized with thymine derivatives is designed and demonstrated. The closing/opening protocol and release of the entrapped guest molecules is related by a photodimerization-cleavage cycle of thymine upon different irradiation. In the system, thymine derivatives with hydrophilicity and biocompatibility were grafted on the pore outlets of MSN. The irradiation with 365 nm wavelength UV light to thymine-functionalized MSN led to the formation of cyclobutane dimer in the pore outlet, subsequently resulting in blockage of pores and strongly inhibiting the diffusion of guest molecules from pores. With 240 nm wavelength UV light irradiation, the photocleavage of cyclobutane dimer opened the pore and allowed the release of the entrapped guest molecules. As a proof-of-the-concept, Ru(bipy)(3)(2+) was selected as the guest molecule. Then the light-responsive loading and release of Ru(bipy)(3)(2+) were investigated. The results indicated that the system had an excellent loading amount (53 MUmol g(-1) MSN) and controlled release behavior (82% release after irradiation for 24 h), and the light-responsive loading and release procedure exhibited a good reversibility. Besides, the light-responsive system loaded with Ru(bipy)(3)(2+) molecule could also be used as a light-switchable oxygen sensor. PMID- 22309361 TI - Angiotensin-I converting enzyme inhibitors suppress angiogenesis and growth of esophageal carcinoma xenografts. AB - It has recently been suggested that angiotensin-I converting enzyme (ACE) inhibitors decrease the risk of cancer. However, studies to date have not investigated esophageal carcinoma. Therefore, we investigated the inhibitory effect of ACE inhibitors on growth of esophageal carcinoma xenografts. We used the EC9706 cell line, which expresses the highest vascular endothelial growth factor (VEGF) mRNA level, to establish xenografts in 21 BALB/c nude mice. The mice were then randomly allocated to receive normal saline, perindopril (4 mg/kg), or benazepril (6 mg/kg). Five weeks later, the nude mice were sacrificed and all tumors were dissected and weighed. The number of microvessels was counted by immunostaining endothelial cells for CD31 and the microvessel density was assessed. The EC9706 cell line showed the highest expression of VEGF mRNA of four esophageal squamous cell carcinoma lines. After treatment, the average tumor inhibitory rate in the benazepril group was 45.4%, which was significantly higher than that of the control group (P < 0.05). Similar findings were observed when we used tumor weight as an index for tumor growth inhibition (P < 0.05). By contrast, there was no significant difference between the perindopril group and the control group (P > 0.05). The benazepril group appeared to show less vascularization than the control group (P < 0.05), but we did not find a significant difference between the perindopril group and the control group (P > 0.05). The EC9706 cell line showed the highest expression of VEGF mRNA level of the four esophageal squamous cell carcinoma cell lines examined. Benazepril inhibited the growth of esophageal carcinoma in vivo. The potential mechanism of benazepril seems to involve suppression of new vessel formation. Therefore, benazepril could be used as an effective agent for the treatment of esophageal carcinoma. PMID- 22309362 TI - Insights from the experiences of older people with hearing impairment in the United Kingdom: recommendations for nurse-led rehabilitation. AB - AIMS AND OBJECTIVES: This study aims to explore, and develop a greater understanding of the experience of living with age-related hearing impairment from the perspectives of older people themselves to highlight possible recommendations for the improvement of hearing aid (HA) services and rehabilitation. BACKGROUND: Hearing impairment (HI) is one of the most common chronic conditions affecting older people. HI can have a huge impact on a wide variety of life factors including physical, mental and social health and can lead to a reduction in quality of life. With the current ageing population, the numbers living with hearing impairment in old age is likely to increase. Currently, the diagnosis of hearing impairment in older people can be slow with individuals living with hearing impairment for around 10 years before being diagnosed. METHODS: The research utilises a descriptive qualitative method in the form of descriptive thematic analysis. Findings are reported from semi-structured interviews with nine participants with self-reported HI, aged 61-93. RESULTS: Themes include; the loss itself, communication, using HAs, isolation, and coping strategies. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The results highlight the need for early diagnosis of HI and the development of nurse-led rehabilitation strategies and support services that address the felt stigma and potentially isolating experiences of older people with HI. PMID- 22309364 TI - Thromboembolism: clinical practice in the face of uncertainty. PMID- 22309365 TI - Serial plotting on customised fundal height charts results in doubling of the antenatal detection of small for gestational age fetuses in nulliparous women. AB - BACKGROUND: The antenatal detection of fetal growth restriction is a focus point of antenatal care. If detected fetal demise may be prevented and perinatal complications could be managed more appropriately. AIMS: To investigate whether introducing serial plotting on customised fundal height charts can increase the detection rate of small for gestational age (SGA) fetuses in low risk nulliparous women attending antenatal clinics in a public teaching hospital in Adelaide, South Australia. METHODS: An observational study was employed to compare SGA detection rates, utilising data from an historical Control group compared to data collected after the study intervention. In the Control group the fundal height (FH) was measured for every antenatal visit and documented in the notes, but not plotted on a chart. The study intervention used serial FH plotting on customised charts, with a dedicated clinical practice guideline and regular audits to increase clinician awareness of the intervention. RESULTS: The antenatal detection rate of SGA was 31/125 (24.8%) in the Control group and 44/87 (50.6%) in the Intervention group (P < 0.001; OR 3.10; 95% CI 1.73-5.57). CONCLUSIONS: Serial plotting of the FH on customised charts supported by a clinical practice guideline resulted in a doubling of the antenatal detection of SGA in nulliparous pregnant women at low risk for SGA. PMID- 22309366 TI - Internal jugular vein thrombosis following ovarian hyperstimulation syndrome. AB - Two cases of women who developed internal jugular vein (IJV) thrombosis associated with ovarian hyperstimulation syndrome (OHSS) are reported in this article. There are 27 cases of IJV thrombosis associated with in vitro fertilisation (IVF) reported in the literature, and in 78% of cases, this outcome was following OHSS. The hypercoagulable state of OHSS increases the risk of venous thromboembolism, and the IJV appears to have a preponderance in uncommon site thrombosis. PMID- 22309367 TI - Re: The RANZCOG College Statement on prophylactic oophorectomy in older women undergoing hysterectomy for benign disease: is the evidence sufficient to change practice? PMID- 22309369 TI - "GOLD or lower limit of normal definition? A comparison with expert-based diagnosis of chronic obstructive pulmonary disease in a prospective cohort study". AB - BACKGROUND: The Global initiative for chronic Obstructive Lung Disease (GOLD) defines COPD as a fixed post-bronchodilator ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) below 0.7. Age-dependent cut-off values below the lower fifth percentile (LLN) of this ratio derived from the general population have been proposed as an alternative. We wanted to assess the diagnostic accuracy and prognostic capability of the GOLD and LLN definition when compared to an expert-based diagnosis. METHODS: In a prospective cohort study, 405 patients aged >= 65 years with a general practitioner's diagnosis of COPD were recruited and followed up for 4.5 (median; quartiles 3.9; 5.1) years. Prevalence rates of COPD according to GOLD and three LLN definitions and diagnostic performance measurements were calculated. The reference standard was the diagnosis of COPD of an expert panel that used all available diagnostic information, including spirometry and bodyplethysmography. RESULTS: Compared to the expert panel diagnosis, 'GOLD-COPD' misclassified 69 (28%) patients, and the three LLNs misclassified 114 (46%), 96 (39%), and 98 (40%) patients, respectively. The GOLD classification led to more false positives, the LLNs to more false negative diagnoses. The main predictors beyond the FEV1/FVC ratio for an expert diagnosis of COPD were the FEV1 % predicted, and the residual volume/total lung capacity ratio (RV/TLC). Adding FEV1 and RV/TLC to GOLD or LLN improved the diagnostic accuracy, resulting in a significant reduction of up to 50% of the number of misdiagnoses. The expert diagnosis of COPD better predicts exacerbations, hospitalizations and mortality than GOLD or LLN. CONCLUSIONS: GOLD criteria over-diagnose COPD, while LLN definitions under-diagnose COPD in elderly patients as compared to an expert panel diagnosis. Incorporating FEV1 and RV/TLC into the GOLD-COPD or LLN-based definition brings both definitions closer to expert panel diagnosis of COPD, and to daily clinical practice. PMID- 22309370 TI - Rhodium complexes of a chelating ligand with imidazol-2-ylidene and pyridin-2 ylidene donors: the effect of C-metalation of nicotinamide groups on uptake of hydride ion. AB - Rhodium complexes of the imidazolylidene (C-im) N-heterocyclic carbene (NHC) ligand, C-im-pyH(+), bearing a nicotinamide cation substituent (pyH(+)) have been targeted for ligand-centered uptake and delivery of hydride ion. This work reveals that rhodium(I) complexes such as [Rh(C-im-pyH(+))(COD)X][PF(6)] (1, a: X = Cl, b: X = I) undergo facile C-metalation of the nicotinamide ring to afford rhodium complexes of a novel chelate ligand, C,C'-im-py, with coordinated imidazolylidene (C(im)) and pyridylidene (C(py)) NHC-donors. Seven examples were characterized and include rhodium(III) monomers of the general formula [Rh(C,C' im-py)L(x)I(2)](z+) (2: z = 1, L = H(2)O or solvent, x = 2; 3, 5, 7: z = 0, L = carboxylate, x = 1) and novel rhodium(II) dimers, the anti/syn-isomers of [Rh(2)(C,C'-im-py)(2)(MUOAc)(2)I(2)] (4-anti/syn). The NMR data, backed by DFT calculations, is consistent with attribution of the C,C'-im-py ligand as a bis(carbene) donor. Single crystal X-ray diffraction studies are reported for 2, 3, 4-anti, 4-syn and 7. Consistently, within the each complex, the Rh-C(im) bond length is shorter than the Rh-C(py) bond length, which is the opposite trend to that expected based on simple electronic considerations. It is proposed that intramolecular steric interactions imposed by different rings in the rigid C,C' im-py chelate ligand dictate the observed Rh-C(NHC) bond lengths. Attempts to add hydride to the C-metalated nicotinamide ring in 3 were unsuccessful. The redox behavior of 3 and 4 and, for comparison, an analogous bis(imidazolylidene)rhodium(III) monomer (8), were characterized by cyclic voltammetry, electron paramagnetic resonance (EPR), and UV-vis spectroelectrochemistry. In 3 and 4, the C-metalated nicotinamide ring is found to exhibit a one-electron reduction process at far lower potential (-2.34 V vs. Fc(+)/Fc in acetonitrile) than the two-electron nicotinamide cation dihydronicotinamide couple found for the corresponding nonmetalated ring (-1.24 V). The C,C'-ligand is electrochemically silent over a large potential range (from -2.3 V to the anodic solvent limit), thus for both 3 and 4 the first reduction processes are metal-centered. For 4-anti, the cyclic voltammetry and UV vis spectrochemical results are consistent with a diamagnetic [Rh(I)Rh(II)](2) tetrameric reduction product. Density functional theory (DFT) calculations were used to further probe the uptake of hydride ion by the nicotinamide ring, both before and after C-metalation. It is found that C-metalation significantly decreases the ability of the nicotinamide ring to take up hydride ion, which is attributed to the "carbene-like" character of a C-metalated pyridylidene ring. PMID- 22309371 TI - Arthroscopic, histological and MRI analyses of cartilage repair after a minimally invasive method of transplantation of allogeneic synovial mesenchymal stromal cells into cartilage defects in pigs. AB - BACKGROUND AIMS: Transplantation of synovial mesenchymal stromal cells (MSCs) may induce repair of cartilage defects. We transplanted synovial MSCs into cartilage defects using a simple method and investigated its usefulness and repair process in a pig model. METHODS: The chondrogenic potential of the porcine MSCs was compared in vitro. Cartilage defects were created in both knees of seven pigs, and divided into MSCs treated and non-treated control knees. Synovial MSCs were injected into the defect, and the knee was kept immobilized for 10 min before wound closure. To visualize the actual delivery and adhesion of the cells, fluorescence-labeled synovial MSCs from transgenic green fluorescent protein (GFP) pig were injected into the defect in a subgroup of two pigs. In these two animals, the wounds were closed before MSCs were injected and observed for 10 min under arthroscopic control. The defects were analyzed sequentially arthroscopically, histologically and by magnetic resonance imaging (MRI) for 3 months. RESULTS: Synovial MSCs had a higher chondrogenic potential in vitro than the other MSCs examined. Arthroscopic observations showed adhesion of synovial MSCs and membrane formation on the cartilage defects before cartilage repair. Quantification analyses for arthroscopy, histology and MRI revealed a better outcome in the MSC-treated knees than in the non-treated control knees. CONCLUSIONS: Leaving a synovial MSC suspension in cartilage defects for 10 min made it possible for cells to adhere in the defect in a porcine cartilage defect model. The cartilage defect was first covered with membrane, then the cartilage matrix emerged after transplantation of synovial MSCs. PMID- 22309373 TI - Polymorphic DNA sequences of the fungal honey bee pathogen Ascosphaera apis. AB - The pathogenic fungus Ascosphaera apis is ubiquitous in honey bee populations. We used the draft genome assembly of this pathogen to search for polymorphic intergenic loci that could be used to differentiate haplotypes. Primers were developed for five such loci, and the species specificities were verified using DNA from nine closely related species. The sequence variation was compared among 12 A. apis isolates at each of these loci, and two additional loci, the internal transcribed spacer of the ribosomal RNA (ITS) and a variable part of the elongation factor 1alpha (Ef1alpha). The degree of variation was then compared among the different loci, and three were found to have the greatest detection power for identifying A. apis haplotypes. The described loci can help to resolve strain differences and population genetic structures, to elucidate host-pathogen interaction and to test evolutionary hypotheses for the world's most important pollinator: the honey bee and one of its most common pathogens. PMID- 22309374 TI - Detection of chicken and turkey meat in meat mixtures by using real-time PCR assays. AB - In this study, TaqMan-based real-time Polymerase Chain Reaction (PCR) techniques were developed for the detection of chicken and turkey meat in raw and heat treated meat mixtures. Primers and TaqMan probe sets were designed to amplify 86 bp and 136 bp fragments for the chicken and turkey species, respectively, on the mitochondrial NADH dehydrogenase subunit 2 gene. In the results, it was possible to detect each species at the level of 0.1 pg template DNA with the TaqMan probe technique without any cross-reactivity with nontarget species (bovine, ovine, donkey, pork, and horse) while the detection level was 1 pg template DNA using conventional PCR. The TaqMan probe assays used in this study allowed the detection of as little as 0.001% level of both species in the experimental meat mixtures, prepared by mixing chicken and turkey meat with beef at different levels (0.001% to 10%). In conclusion, TaqMan probe assays developed in this research are promising tools in the specific identification and sensitive quantification of meat species even in the case of heat-treated meat products, and suitable for a rapid, automated, and routine analysis. PMID- 22309375 TI - The future of nursing revisited. PMID- 22309376 TI - Concept analysis: case management role confusion. AB - AIM: This paper is a report on the concept of role confusion as it applies to nurse case management. BACKGROUND: Nurse case managers (NCMs) play an important role in the delivery of quality health care. There has been considerable discussion and debate as to the exact role of the NCM. Research has not produced a conceptual model for the NCM. A clear and concise definition of the role of the NCM is not available from published literature. METHODS: This analysis was conducted using the Walker and Avant method. Literature searches were conducted using Cumulative Index of Nursing and Allied Health, ProQuest, PsychInfo, PubMed, Academic Search Premier, and ERIC. Time line covered the period of 1980-2010. FINDINGS: Based on the analysis, role confusion occurs when there is no clear set of expectations for the NCM. Organizations have created positions that often are not patient centered and underutilize the nursing aspect. Nursing literature does not report significant investigation of the phenomena of role confusion in nurse case management. CONCLUSION: There needs to be a conceptual model for the role of the NCM. A skill set designated exclusively to nurses who practice case management would emphasize the patient-nurse relationship and provide clarity of the role and function of NCMs. PMID- 22309377 TI - Critical access health care: a concept analysis. AB - PURPOSE: The purpose of this paper is to provide a concept analysis of critical access health care. A common understanding of critical access health care would benefit those who legislate, provide, and consume health care. METHODS: A review of the literature was conducted using an identical set of search terms that yielded a variety of sources; however, none were specifically related to critical access health care. FINDINGS: No literature of concept analysis of critical access health care could be found. CONCLUSIONS: A concrete and measurable understanding of the concept will provide a common foundation to assist public and private entities in developing viable methods to understand healthcare policies, problems related to access, disparities in health care, and ways to increase health promotion and disease prevention. PMID- 22309378 TI - Clinical trial nurse's role in safety reporting. AB - The clinical trial nurse (CTN) can have a substantial amount of responsibility for clinical trials and can perform many roles in the management of clinical trials. Although new opportunities for the registered nurse in clinical trials have emerged in recent years, there remains to be a dearth of literature surrounding the important roles of the CTN in clinical trials. The CTN is a specialty-nursing role that is unfamiliar to many, including some nurses. Therefore, it is important to address this gap in the literature and enlighten the nursing profession and others about the roles of the nurse in clinical trials. This article aims to explore and provide an overview of the CTN's role in safety reporting. Safety reporting is a significant component of clinical trials by protecting the rights, safety, and welfare of subjects. The CTN integrates and utilizes his or her knowledge, experience, skills, and sound ethical principles when performing the duties of this role. This allows the CTN to be a vital member in the safety-reporting process and in the protection of subjects. PMID- 22309379 TI - A review of the literature: evaluating dietary intake of Filipino Americans at risk for type 2 diabetes. AB - The purpose of this literature review is to investigate the research on the dietary intake of Filipino Americans. Evaluating the dietary practices of Filipino Americans may have an effect on the development of type 2 diabetes. Data collection was obtained, and four databases were included: Pub Medical, Cumulative Index of Nursing and Allied Health Literature, Journals at OVID, and Medline. The key words used in the search were "diet,""type 2 diabetes," and "Filipinos." A total of nine articles were relevant and met the inclusion criteria. The following articles were excluded: studies in a foreign language, letters to the editor, and program descriptions. PMID- 22309380 TI - Simulating care: technology-mediated learning in twenty-first century nursing education. AB - PROBLEM: The increased reliance on simulation classrooms has proven successful in learning skills. Questions persist concerning the ability of technology-driven robotic devices to form and cultivate caring behaviors, or sufficiently develop interactive nurse-client communication necessary in the context of nursing. METHODS: This article examines the disconnects created by use of simulation technology in nursing education, raising the question: "Can learning of caring-as being, be facilitated in simulation classrooms?" FINDINGS: We propose that unless time is spent with human beings in the earliest stages of nursing education, transpersonal caring relationships do not have space to develop. Learning, crafting, and maturation of caring behaviors threatens to become a serendipitous event or is no longer perceived as an essential characteristic of nursing. CONCLUSIONS: Technology does not negate caring-the isolation it fosters makes transpersonal caring all the more important. We are called to create a new paradigm for nursing education that merges Nightingale's vision with technology's promise. PMID- 22309382 TI - Calculating nurse staffing in community mental health and community health settings in South Australia. AB - AIM: The article reports the development of and data from a preliminary evaluation of a staffing methodology equalization tool (SMET) designed for the South Australian Department of Health to equalize the workload of community mental health and community health nurses working within multidisciplinary teams. BACKGROUND: Shorter admissions, increasing patient acuity, and shortages of beds have intensified the work of community nurses. Existing workload models have limitations for community nursing settings. METHOD: A workload tool for community mental health and community nurses was developed in consultation with a reference group of nurses. A trial was conducted at six sites, and the tool was evaluated using qualitative and quantitative data. RESULTS: The tool increased transparency and equity of workloads in community teams and provided a means of reducing workload through demonstration of a capacity to take new clients, however, further work is required to factor the intensity of caseload into the tool. CONCLUSIONS: The tool needs further evaluation to determine its applicability to a range of clinical settings. PMID- 22309381 TI - Wellness in older adults: a concept analysis. AB - PURPOSE: The purpose of this analysis is to examine the concept of wellness within the context of older adulthood. Identifying characteristics of wellness will clarify and develop conceptual strengths and limitations, providing a step toward evaluating its relevance in older adults and increasing utility in geriatric nursing. ORGANIZING FRAMEWORK: Rodger's evolutionary perspective. METHODS: Computer and manual searches were conducted of articles in the English language from 1950 to 2010, addressing wellness across the life span or among older adult populations. An inductive analysis of articles produced descriptive themes. FINDINGS: A historical time line traced the evolution of the wellness concept and its operationalization. Wellness has evolved from a little used concept to one commonly applied across many industries. Antecedents, attributes, and consequences of wellness are described. Concepts related to wellness are also identified. CONCLUSIONS: This concept analysis adds clarity to wellness in older adults. The state of wellness development as a concept in geriatric nursing is moving from conceptualization to use and testing in nursing theory and interventions. Increased knowledge of wellness will enable geriatric nurses to discover the strengths of older adults thereby promoting their ongoing growth and development while simultaneously guiding care for their changing and diverse health. PMID- 22309383 TI - The relationships between safety climate, teamwork, and intent to stay at work among Jordanian hospital nurses. AB - PURPOSE: The purpose of the present study is to examine the relationships among safety climate, teamwork, and intent to stay at work as perceived by Jordanian hospital nurses. METHODS: A descriptive correlational design was used to investigate these relationships among a convenience sample of 381 hospital nurses. Data were collected through a self-administered questionnaire that included the Safety Climate and Teamwork Scale and the McCain's Intent to Stay Scale. Descriptive statistics, Pearson correlation, analysis of variance, and hierarchical regression analysis were used to analyze the data. RESULTS: The findings showed (a) a strong positive correlation between safety climate and teamwork; and (b) moderate positive correlations between safety climate and intent to stay at work, and between teamwork and intent to stay at work. Moreover, the overall model of hierarchical regression showed that 45% of the variation in the level of intent to stay at work was explained by background variables, leadership styles, decision-making styles, and safety climate. CONCLUSION: The findings emphasized the positive effect of safety climate and teamwork on the level of nurses' intent to stay. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse administrators should design and implement strategies that create a culture of safety climate and teamwork in their organizations. PMID- 22309385 TI - Effectiveness of chin-down posture to prevent tracheal aspiration in dysphagia secondary to acquired brain injury. A videofluoroscopy study. AB - BACKGROUND: The chin-down posture is generally recommended in patients with neurogenic dysphagia to prevent tracheal aspiration; however, its effectiveness has not been demonstrated. AIM: To videofluoroscopically (VDF) assess the effectiveness of chin-down posture to prevent aspiration in patients with neurogenic dysphagia secondary to acquired brain injury. METHODS: Randomized, alternating, cross-over study (with and without the chin-down posture) in 47 patients with a VDF diagnosis of aspiration [31 stroke, 16 traumatic brain injury (TBI)] and 25 controls without aspiration (14 stroke, 11 TBI). KEY RESULTS: During the chin-down posture, 55% of patients avoided aspiration (40% preswallow aspiration and 60% aspiration during swallow). The percentage was similar in both etiologies (58% stroke and 50% TBI). Fifty-one percent of patients had silent aspiration; of these, 48% persisted with aspiration while in the chin-down posture. A statistically significant relationship was found between the existence of pharyngeal residue, cricopharyngeal dysfunction, pharyngeal delay time and bolus volume with the persistence of aspiration. The chin-down posture did not change swallow biomechanics in patients without aspiration. CONCLUSIONS & INFERENCES: Only half the patients with acquired brain injury avoided aspiration during cervical flexion; 48% of silent aspirators continued to aspire during the maneuver. Several videofluoroscopic parameters were related to inefficiency of the maneuver. Therefore, the indication for chin-down posture should be evaluated by videofluoroscopic examination. PMID- 22309386 TI - Unrecognized failure of a narrow caliber defibrillation lead: the role of defibrillation threshold testing in identifying an unprotected individual. AB - In this case report we describe a short circuit in the Riata 1570 defibrillator lead (Riata 1570, St. Jude Medical, St. Paul, MN, USA) that was unsuspected owing to normal lead parameters until defibrillator threshold testing at the time of elective generator change. On this occasion, the short circuit manifested as unsuccessful defibrillation of ventricular fibrillation with immediate battery depletion. This report adds weight to existing concerns over narrow caliber leads, it draws attention to the possibility of lead malfunction despite unremarkable interrogation, and lastly it highlights the potential role of routine defibrillator threshold testing, particularly at elective generator change (an issue that remains sparingly addressed in the existing literature). PMID- 22309387 TI - Superior mesenteric arterial branch occlusion causing partial jejunal ischemia: a case report. AB - INTRODUCTION: Ischemic bowel disease comprises both mesenteric ischemia and colonic ischemia. Mesenteric ischemia can be divided into acute and chronic ischemia. These are two separate entities, each with their specific clinical presentation and diagnostic and therapeutic modalities. However, diagnosis may be difficult due to the vague symptomatology and subtle signs. CASE PRESENTATION: We report the case of a 68-year-old Caucasian woman who presented with abdominal discomfort, anorexia, melena and fever. A physical examination revealed left lower quadrant tenderness and an irregular pulse. Computed tomography of her abdomen as well as computed tomography enterography, enteroscopy, angiography and small bowel enteroclysis demonstrated an ischemic jejunal segment caused by occlusion of a branch of the superior mesenteric artery. The ischemic segment was resected and an end-to-end anastomosis was performed. The diagnosis of segmental small bowel ischemia was confirmed by histopathological study. CONCLUSION: Mesenteric ischemia is a pathology well-known by surgeons, gastroenterologists and radiologists. Acute and chronic mesenteric ischemia are two separate entities with their own specific clinical presentation, radiological signs and therapeutic modalities. We present the case of a patient with symptoms and signs of chronic mesenteric ischemia despite an acute etiology. To the best of our knowledge, this is the first report presenting a case of acute mesenteric ischemia with segmental superior mesenteric artery occlusion. PMID- 22309388 TI - Prostaglandin E1 dose-dependently promotes stability of atherosclerotic plaque in a rabbit model. AB - This study evaluated the effect of prostaglandin E1 (PGE1) on the stability of atherosclerotic plaque. A vulnerable plaque model was established in rabbits, using balloon injury combined with a high-cholesterol diet. The rabbits were distributed into a control group, a low-dose PGE1 treatment group, a moderate dose PGE1 treatment group, a high-dose PGE1 treatment group, and a simvastatin treatment group, with treatments lasting for 4 weeks. At week 13 (at the end of the experiments), atherosclerotic plaque was triggered by injection of Russell's viper venom (Chinese) and histamine. Serological, pathological, immunohistochemical, and gene-expression studies were subsequently performed. PGE1 treatment did not alter serum lipid levels; however, PGE1 dose-dependently increased the thickness of the fibrous caps, and decreased the plaque vulnerability index. The plaque contents of macrophage- and the mRNA levels of monocyte-chemotactic protein-1, matrix metalloproteinase-1, and matrix metalloproteinase-9 were markedly reduced in all of the PGE1 treatment groups, with the high-dose of PGE1 being more effective than the simvastatin treatment. These findings suggest that PGE1 dose-dependently enhances the stability of atherosclerotic plaque. The high-dose of PGE1 presented more protection in terms of inhibiting macrophage accumulation and inflammatory expression in plaque. Our findings suggest a novel drug for the treatment of atherosclerosis. PMID- 22309389 TI - Update: malaria, U.S. Armed Forces, 2011. AB - U.S. service members are at risk of malaria when they are assigned to endemic areas (e.g., Korea), participate in operations in endemic areas (e.g., Afghanistan, Africa) and visit malarious areas during personal travel. In 2011, 124 service members were reported with malaria. Nearly three-fourths of cases were presumably acquired in Afghanistan (n=91) and one-fifth were considered acquired in Africa (n=24). One-quarter of cases were caused by P. vivax and one fifth by P. falciparum (including 6 Afghanistan-acquired infections); most cases were reported as "unspecified" malaria. Malaria was diagnosed/reported from 51 different medical facilities in the United States, Afghanistan, Kyrgyzstan, Iraq, Germany and Korea. Providers of care to military members should be knowledgeable regarding and vigilant for clinical presentations of malaria outside of endemic areas. PMID- 22309390 TI - Sources of variability of estimates of malaria case counts, active and reserve components, U.S. Armed Forces. AB - Each January, the Medical Surveillance Monthly Report (MSMR) estimates numbers of malaria infections among U.S. service members using a surveillance case definition to identify "malaria cases". These cases include individuals with a hospital discharge diagnosis of malaria and those who were reported with malaria through military notifiable event reporting systems. This report compares the MSMR surveillance case definition with other proposed case definitions to demonstrate the degree to which estimates of numbers of malaria cases are dependent upon clinical settings, data sources and case-defining rules used to produce such estimates. For example, including outpatient diagnoses as malaria cases would more than double the 2010 case count. As compared with cases defined using other proposed case definitions, many more MSMR-defined cases had records of a specific Plasmodium species, a laboratory test for malaria and recent travel to a malaria-endemic country. Interpretations of the results of MSMR reports should consider how "cases" are defined. PMID- 22309391 TI - Images in health surveillance: malaria vectors and malaria testing. PMID- 22309392 TI - Editorial: malaria in the U.S. armed forces: a persistent but preventable threat. PMID- 22309393 TI - Historical snapshot: development of the hepatitis A vaccine. PMID- 22309395 TI - Bereavement care for older people in healthcare settings: qualitative study of experiences. AB - AIM: This study aimed to explore the experiences of healthcare staff of caring for bereaved older people, and older people's experiences of bereavement care. BACKGROUND: Loss through death of close family members, partners and friends inhibits the physical, emotional and social well being of older people. The rising population of older people and pressure on healthcare services to reduce costs indicate the necessity of developing strategies that enable coping and independence. DESIGN: A qualitative design drawing on phenomenological methodology was used to understand interactions between healthcare staff and bereaved older people. The study was set in hospital wards, general practice and community nursing teams, and care homes. Healthcare staff and a sample of recently bereaved older people participated. METHODS: Purposive sampling took place to recruit staff with a range of roles, and older people who were 65 years of age or more, and bereaved of a family member or friend for between 6 months and 5 years. Participants took part in in-depth interviews, and data were analysed systematically. RESULTS: Thirty-nine participants were recruited, and three key themes arose from the data: (i) Bereavement care depends on an established relationship between healthcare staff and the patient's relatives; (ii) Preparation for the relative's death may not equate to being prepared for bereavement; (iii) The 'Open Door' to bereavement care is only slightly ajar. CONCLUSIONS: The study identified the interactions of healthcare staff with bereaved older people in terms of the bereavement journey. Staff demonstrated awareness of difficulties the bereaved person may encounter and showed commitment to providing support. However, lack of flexibility in services restricts meaningful interactions. IMPLICATIONS FOR PRACTICE: (i) Healthcare staff may identify gaps in services in terms of preparing relatives and follow-up post bereavement; (ii) Therapeutic relationships between staff and relatives enable ongoing support; (iii) Development of practice guidelines is a key consideration. PMID- 22309397 TI - Sum frequency generation and coherent anti-Stokes Raman spectroscopic studies on plasma-treated plasticized polyvinyl chloride films. AB - Polyvinyl chloride (PVC) is a widely used polymer to which various phthalates are extensively applied as plasticizers. PVC materials are often treated with plasma to vary the hydrophobicity or for cleaning purposes, but little is known of the nature of the surface molecular structures after treatment. This research characterizes molecular surface structures of PVC and bis-2-ethylhexyl phthalate (DEHP)-plasticized PVC films in air before annealing, after annealing, and after exposure to air-generated glow discharge plasma using sum frequency generation (SFG) vibrational spectroscopy. In addition, we compare the vibrational molecular signatures on the surfaces of PVC with DEHP (at a variety of percent loadings) to those of the bulk detected using coherent anti-Stokes Raman scattering (CARS). X ray photoelectron spectroscopy (XPS) and contact angle measurements have been used to analyze PVC surfaces to supplement SFG data. Our results indicate that DEHP was found on the surfaces of PVC films even at low weight percentages (5 wt %) and that DEHP segregates on surfaces after annealing. The treatment of these films with glow discharge plasma resulted in surface-sensitive reactions involving the removal of chlorine atoms, the addition of oxygen atoms, and C-H bond rearrangement. CARS data demonstrate that the bulk of our films remained undisturbed during the plasma treatment. For the first time, we probed the molecular structure of the surface and the bulk of a PVC material using combined SFG and CARS studies on the same sample in exactly the same environment. In addition, the methodology used in this research can be applied to characterize various plasticizers in a wide variety of polymer systems to understand their surface and bulk structures before and after systematic applications of heat, plasma, or other treatments. PMID- 22309398 TI - Malignancy-associated chylothorax: a 20-year study of 18 patients from a single institution. AB - Malignancy-associated chylothorax is a rare manifestation with uncertain characteristics and clinical significance. We segregated 18 patients into malignant lymphoma (n= 11) and solid malignancy (n= 7) groups to analyse the characteristics, treatment response and prognostic value of malignancy-associated chylothorax. Diagnosis of chylothorax was confirmed by a triglyceride concentration of >110 mg/dL or by the presence of chylomicrons in the pleural effusion. Concentrations of glucose, protein and lactate dehydrogenase did not differ significantly between the malignant lymphoma and solid malignancy groups. Although not statistically significant (P= 0.25), 90.9% malignant lymphoma patients and 57.1% solid malignancy patients had exudates. The cytology diagnostic rate in the malignant lymphoma and solid malignancy groups was 20.0% and 33.3% respectively (P > 0.99). After chemotherapy, six malignant lymphoma patients achieved complete remission, with simultaneous chylothorax disappearance. The overall survival rate at 12 and 24 months in the malignant lymphoma group was 54.5% and 36.4% respectively, while that in the solid malignancy group was 35.7% and 0% respectively. Malignant lymphoma was the chief cause of chylothorax in our cohort. Effective lymphoma treatment, lacking supplementary interventions, is essential for treating chylothorax in malignant lymphoma patients. Chylothorax indicates extremely limited life expectancy for solid malignancy patients. PMID- 22309399 TI - Chronic treatment of haloperidol induces pathological changes in striatal neurons of guinea pigs: a light and electron microscopical study. AB - In the present work, we investigated whether there would be any change in histological structure of striatal neurons after haloperidol applications at different doses. Adult male guinea pigs were treated once-daily with saline (group 4, control) or haloperidol during 6 weeks, and the dose was 1, 2, or 3 mg/kg (groups 1, 2, and 3, respectively). After treatment, all animals were anesthetized and striata were dissected and examined. When striata were evaluated histologically, dark neurons and some degenerating striatal neurons had distinctive morphological changes consistent with cell death, including reduced neuronal size with nuclear and cytoplasmic shrinkage. Also, in sections of striata in groups 1 and 2, but not in group 3, more glial cells were observed than in those of the control group. In all treated groups, fibrous content of intersititium was paralelly increased by increasing dose. Ultrastructural investigation of striatal neurons in haloperidol-treated rats showed notched nuclei and many lysosomes. Moreover, degeneration of myelin, scarce microglial macrophages, expansion of nuclear intermembranous space, degenerated mitochondria, and vacuoles were found. Also, cytoplasmic swelling, lysosomes, and apoptotic bodies were present. These results suggest that haloperidol treatment may lead to damage in neurons via the necrotic process in both low- and high-dose applications. PMID- 22309400 TI - Fruit cuticle lipid composition and fruit post-harvest water loss in an advanced backcross generation of pepper (Capsicum sp.). AB - To understand the role of fruit cuticle lipid composition in fruit water loss, an advanced backcross population, the BC(2)F(2) , was created between the Capsicum annuum (PI1154) and the Capsicum chinense (USDA162), which have high and low post harvest water loss rates, respectively. Besides dramatic differences in fruit water loss, preliminary studies also revealed that these parents exhibited significant differences in both the amount and composition of their fruit cuticle. Cuticle analysis of the BC(2)F(2) fruit revealed that although water loss rate was not strongly associated with the total surface wax amount, there were significant correlations between water loss rate and cuticle composition. We found a positive correlation between water loss rate and the amount of total triterpenoid plus sterol compounds, and negative correlations between water loss and the alkane to triterpenoid plus sterol ratio. We also report negative correlations between water loss rate and the proportion of both alkanes and aliphatics to total surface wax amount. For the first time, we report significant correlations between water loss and cutin monomer composition. We found positive associations of water loss rate with the total cutin, total C(16) monomers and 16 dihydroxy hexadecanoic acid. Our results support the hypothesis that simple straight-chain aliphatic cuticle constituents form more impermeable cuticular barriers than more complex isoprenoid-based compounds. These results shed new light on the biochemical basis for cuticle involvement in fruit water loss. PMID- 22309402 TI - Unusual cationic tris(dimethylsulfide)-substituted closo-boranes: preparation and characterization of [1,7,9-(Me2S)3-B12H9] BF4 and [1,2,10-(Me2S)3-B10H7] BF4. AB - Rational syntheses of trisubstituted sulfur-bearing closo-boranes are presented. In the development of these syntheses unusual cationic closo-boranes [1,7,9 (Me(2)S)(3)-B(12)H(9)](+) (3) and [1,2,10-(Me(2)S)(3)-B(10)H(7)](+) (4) have been identified. These were initially recognized to be intermediates in the formation of the neutral trisubstituted species 1,7-(Me(2)S)(2)-9-(MeS)-B(12)H(9) (1) and 1,10-(Me(2)S)(2)-2-(MeS)-B(10)H(7) (2), respectively. Stable tetrafluoroborate salts were prepared and isolated, and their structures are presented. They are believed to represent the first structural determinations of cationic borane clusters of any type. PMID- 22309403 TI - E. coli o157:H7 population reduction from alfalfa seeds with malic acid and thiamine dilauryl sulfate and quality evaluation of the resulting sprouts. AB - It has been reported that washing seeds with a 20000 ppm Ca(OCl)(2) solution as recommended by the U.S. Food and Drug Administration is unable to eliminate E. coli cells attached to seed surfaces, and the bacterial cells that have survived a sanitation wash can proliferate during sprouting to a high population. The objectives of this research were to examine the efficacy of malic acid (MA) and thiamine dilauryl sulfate (TDS) combined treatments on the inactivation of E. coli O157:H7 on alfalfa seeds, to study the growth of the remaining E. coli cells during sprouting, and to evaluate the sprout quality. When 10 g of inoculated alfalfa seeds were washed in a 10% MA-1% TDS solution, a complete elimination of E. coli was achieved. The same result was observed by washing the seeds in a 20000 ppm Ca(OCl)(2) solution. However, when the seed size was increased to 50 g while maintaining the same seed-to-sanitizer ratio, both the MA + TDS and the 20000 ppm chlorine washes failed to completely inactivate the E. coli cells on the seeds. Nevertheless, the 10% MA-1% TDS solution was significantly more effective in E. coli count reduction compared to the 20000 ppm chlorine wash. The E. coli O157:H7 cells remaining on the seeds after treatments with both sanitizers grew up to 7 to 8 log CFU/g sprout after 96 h of sprouting. Under the treatment conditions used in this study, none of the treatments resulted in significant differences in germination rate, yield, or quality of the sprouts. PRACTICAL APPLICATION: The malic acid (MA) and thiamine dilauryl sulfate (TDS) combined treatment may provide a new solution to secure the microbial safety of seeds and sprouts. An important finding of this study is that seed sample size has a significant impact on the inactivation of E. coli O157:H7 on alfalfa seeds. The microbial inactivation results obtained in a laboratory set-up cannot be directly applied to a large scale operation. A validation test on the large scale has to be performed to evaluate the efficacy of the sanitizer. PMID- 22309404 TI - Stimulation of gastric slow waves with manual acupuncture at acupuncture points ST36 and PC6--a randomized single blind controlled trial. AB - BACKGROUND: To investigate the effects of stimulated and non-stimulated manual acupuncture at ST36 and PC6 on gastric myoelectrical activity and autonomic function. METHODS: A total of 65 healthy volunteers were randomly assigned to a 1: 1: 2 ratio to receive either 15 min of verum acupuncture (VA) with stimulation followed by 15 min of VA without stimulation (nsVA), or 15 min of nsVA followed by 15 min of VA with stimulation (sVA), or 30 min of sham acupuncture (SA). Measures of autonomic function included electrogastrogram, electrocardiogram, impedance cardiography and assessment of blood pressure, breathing frequency, and electrodermal activity. Outcome parameters were compared between VA and SA, and between sVA and nsVA. The percentage of regular gastric slow waves (normogastria) was defined as the primary outcome. KEY RESULTS: The percentage of normogastria was not significantly different between VA and SA. Differences in secondary outcomes such as power spectrum of gastric slow waves and heart rate variability parameters were pronounced in the comparison of sVA and nsVA. During sVA, the percentage of normogastria was lower (P = 0.005), the percentage of bradygastria was higher (P = 0.003) and power ratio was higher (P < 0.001), systolic blood pressure was lower (P = 0.039) and RMSSD was higher (P < 0.001) as compared with nsVA. CONCLUSIONS & INFERENCES: Our study suggests that manual stimulation of acupuncture needles at ST36 and PC6 affects gastric myoelectrical as well as cardiac activities in healthy volunteers. The effect of stimulation in acupuncture deserves further investigation. PMID- 22309405 TI - Step-by-step management of refractory gastresophageal reflux disease. AB - Up to a third of the patients who receive proton pump inhibitor (PPI) once daily will demonstrate lack or partial response to treatment. There are various mechanisms that contribute to PPI failure and they include residual acid reflux, weakly acidic and weakly alkaline reflux, esophageal hypersensitivity, and psychological comorbidity, among others. Some of these underlying mechanisms may coincide in the same patient. Evaluation for proper compliance and adequate dosing time of PPIs should be the first management step before ordering invasive diagnostic tests. Doubling the PPI dose or switching to another PPI is the second step of management. Upper endoscopy and pH testing appear to have limited diagnostic value in patients who failed PPI treatment. In contrast, esophageal impedance with pH testing (multichannel intraluminal impedance MII-pH) on therapy appears to provide the most insightful information about the subsequent management of these patients (step 3). In step 4, treatment should be tailored to the specific underlying mechanism of patient's PPI failure. For those who demonstrate weakly acidic or weakly alkaline reflux as the underlying cause of their residual symptoms, transient lower esophageal sphincter relaxation reducers, endoscopic treatment, antireflux surgery and pain modulators should be considered. In those with functional heartburn, pain modulators are the cornerstone of therapy. PMID- 22309406 TI - Lipase A gene transcription in Pseudomonas alcaligenes is under control of RNA polymerase sigma54 and response regulator LipR. AB - Initial analysis has shown that the transcription of the Pseudomonas alcaligenes lipA gene, which encodes an extracellular lipase, is governed by the LipQR two component system consisting of sensor kinase LipQ and DNA-binding regulator LipR. This study further analyzes lipA gene expression and demonstrates that the RNA polymerase sigma54 is involved in the transcription. Purified LipR has an ATPase activity that is stimulated by the presence of lipA promoter DNA. Surface plasmon resonance measurements with purified and in vitro phosphorylated LipR reveal that phosphorylation of LipR is required for specific binding to the upstream activating sequence of the lipA promoter. Furthermore, mass spectrometric analysis combined with mutagenesis demonstrates that Asp52 is the phosphorylated aspartate. This analysis exposes LipR as a prominent member of the growing family of bacterial enhancer-binding proteins. PMID- 22309407 TI - Management of endocardial leads in the left ventricle (LV). PMID- 22309408 TI - Effects of imidazolines on neurogenic contraction in isolated urinary bladder detrusor strips from rabbit. AB - Moxonidine and clonidine, which are imidazoline compounds, are sympathetic modulators used as centrally acting antihypertensive drugs. Moxonidine, clonidine, and agmatine produce extensive effects in mammalian tissues via imidazoline recognition sites (or receptors) or alpha(2)-adrenoceptors. To investigate the effects of imidazolines on the function of the urinary bladder, we tested the effects of moxonidine, clonidine, and agmatine on the neurogenic contraction induced by electric field stimulation, and on the post-synaptic receptors in isolated urinary bladder detrusor strips from rabbit. Both moxonidine at 1.0-10.0 umol/L and clonidine at 0.1-10.0 umol/L inhibited electric field-stimulation-induced contraction in a concentration-dependent manner, but not agmatine (10.0-1000.0 umol/L). Both moxonidine and clonidine failed to affect carbachol or adenosine-triphosphate-induced contractions; however, 1000.0 umol/L agmatine significantly increased these contractions. Our study indicates that (i) moxonidine and clonidine produce a concentration-dependent inhibition of the neurogenic contractile responses to electric field stimulation in isolated detrusor strips from male New Zealand rabbits; (ii) post-synaptic muscarinic receptor and purinergic receptor stimulation are not involved in the responses of moxinidine and clonidine in this study; (iii) the inhibitory effects of these agents are probably not mediated by presynaptic imidazoline receptors. PMID- 22309409 TI - Synthesis of O-spiro-C-aryl glycosides using organocatalysis. AB - An organocatalysis strategy has been developed toward the synthesis of O-spiro-C aryl glycosides with different configurations in the sugar part. This strategy has been extended to the synthesis of the Papulacandin class of compounds. PMID- 22309410 TI - Is burnout static or dynamic? A career transition perspective of employee burnout trajectories. AB - Despite decades of theory and empirical research on employee burnout, its temporal and developmental aspects are still not fully understood. This lack of understanding is problematic because burnout is a dynamic phenomenon and burnout interventions may be improved by a greater understanding of who is likely to experience changes in burnout and when these changes occur. In this article, we advance existing burnout theory by articulating how the 3 burnout dimensions should differ in their pattern of change over time as a result of career transition type: organizational newcomers, internal job changers (e.g., promotions or lateral moves), and organizational insiders (i.e., job incumbents). We tested our model in a broad sample of 2,089 health care employees, with 5 measurement points over 2 years. Using random coefficient modeling, we found that burnout was relatively stable for organizational insiders but slightly dynamic for organizational newcomers and internal job changers. We also found that the dimensions of emotional exhaustion and depersonalization were more sensitive to career transition type than reduced personal accomplishment. Finding some differences among different types of employees as well as the dimensions of burnout may begin to explain longstanding inconsistencies between theory and research regarding the dynamics of burnout, offering directions for future research that address both dynamism and stability. PMID- 22309412 TI - Sickle cell and renal transplant: a national survey and literature review. AB - Sickle cell disease is an inherited, structural hemoglobin defect with multisystemic sequelae including renal failure. Patients with sickle cell disease are thought to benefit from renal transplant, but the long-term outcomes in such patients are unclear and have not been supported by any large prospective studies. Similarly, the renal morbidity and outcome after transplant in patients with sickle cell trait is also unclear. There is little evidence concerning living donation in donors with sickle cell disease or sickle cell trait, either for the donor health or for the graft outcome, and there are no United Kingdom guidelines. The aim of this study is to review the evidence surrounding renal transplant in recipients and donors with sickle syndromes and to determine the attitudes and current practices of United Kingdom transplant centers to performing such operations. PMID- 22309411 TI - Sensitive and rapid quantification of C-reactive protein using quantum dot labeled microplate immunoassay. AB - BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) assay is of great clinical importance in predicting risks associated with coronary heart disease. Existing hs-CRP assays either require complex operation or have low throughput and cannot be routinely implemented in rural settings due to limited laboratory resources. METHODS: We developed a novel hs-CRP assay capable of simultaneously quantifying over 90 clinical samples by using quantum dots-labeled immunoassay within a standard 96-well microplate. The specificity of the assay was enhanced by adopting two monoclonal antibodies (mAbs) that target distinct hs-CRP epitopes, serving as the coating antibody and the detection antibody, respectively. In the presence of hs-CRP antigen, the fluorescence intensity of the mAb-Ag-mAb sandwich complex captured on the microplate can be read out using a microplate reader. RESULTS: The proposed hs-CRP assay provides a wide analytical range of 0.001-100 mg/L with a detection limit of 0.06 (0.19) MUg/L within 1.5 h. The accuracy of the proposed assay has been confirmed for low coefficient of variations (CVs), 2.27% (intra-assay) and 8.52% (inter-assay), together with recoveries of 96.7-104.2%. Bland-Altman plots of 104 clinical samples exhibited good consistency among the proposed assay, commercial high sensitivity ELISA, and nephelometry, indicating the prospects of the newly developed hs-CRP assay as an alternative to existing hs-CRP assays. CONCLUSION: The developed assay meets the needs of the rapid, sensitive and high-throughput determination of hs-CRP levels within a short time using minimal resources. In addition, the developed assay can also be used to detect and quantify other diagnostic biomarkers by immobilizing specific monoclonal antibodies. PMID- 22309413 TI - Prediction of long-term kidney failure in renal transplant with chronic allograft dysfunction using stage-specific hazard rates. AB - OBJECTIVES: The process of kidney failure in renal transplant recipients with chronic allograft dysfunction is characterized by a progressive decline in glomerular filtration rate over time that it is determined by the 5-stage model. This study used stage-based statistical survival analysis to predict graft survival in renal transplant recipients with chronic allograft dysfunction. MATERIALS AND METHODS: In a single-center, retrospective study, 214 renal transplant recipients with chronic allograft dysfunction were investigated at a university hospital in Iran from 1997 to 2005. At each patient visit, kidney function was assessed using glomerular filtration rate and stage of disease. RESULTS: The estimated stage-specific hazard rates of disease progression are stage one, 453.936; stage two, 485.040; stage three, 545.808; and stage four; 649.488 per 1000 person-years. The estimated mean times in each stage were as follows: kidney damage with normal or increased glomerular filtration rate, 26.43 months; kidney damage with mildly decreased glomerular filtration rate, 24.74 months; moderate kidney disease, 21.98 months; and severe kidney disease; 18.48 months. These estimates yield a mean time from stage 1 to kidney failure of 91.63 months. The probability of graft survival was predicted using estimated stage specific hazard rates. The 18th, 58th, 118th, and 155th months death-censored graft survival probabilities were 0.99, 0.75, 0.25, and 0.10. CONCLUSIONS: In this method of survival analysis, we can determine a statistical model according to a real clinical model in renal transplant recipients with chronic allograft dysfunction. It enables us to determine the stage-specific hazard rates of disease progression. These findings can help nephrologists to understand the kidney disease process and better predict graft survival. PMID- 22309414 TI - Cystatin C as a marker of glomerular filtration rate in voluntary kidney donors. AB - OBJECTIVES: Cystatin C is emerging as an endogenous marker of glomerular filtration rate. This study sought to assess the usefulness of serum cystatin C as a marker of glomerular filtration rate in comparison with serum creatinine and serum creatinine-based glomerular filtration rate estimations in voluntary kidney donors. MATERIALS AND METHODS: Serum cystatin C and serum creatinine were estimated in 35 voluntary kidney donors. Glomerular filtration rate was estimated using: (1) Cockcroft-Gault method normalized to 1.73 m(2) of body surface area, (2) 4-variable Modification of Diet in Renal Diseases formula, and (3) (99m)Tc DTPA double plasma sampling method. Glomerular filtration rate-double plasma sampling method was used as a reference value. Results were expressed as means +/ SD. RESULTS: The mean age of the participants was 44.23 +/- 8.61 years old (19 women, 16 men). The mean serum creatinine was 0.83 +/- 0.14 mg/dL, and the mean serum cystatin C was 0.71 +/- 0.12 mg/L. Serum cystatin C showed significant correlation with serum creatinine (r = 0.864; P < .001). Glomerular filtration rate-MDRD showed the strongest correlation with glomerular filtration rate double plasma sampling method (r = 0.93; P < .001), followed by glomerular filtration rate-Cockcroft-Gault (r = 0.76; P < .001 ), serum creatinine (r = - 0.68; P < .001), and serum cystatin C (r = - 0.59; P < .001). The mean serum cystatin C values were 22.6% higher in men than in women. There was a significant correlation of serum cystatin C with glomerular filtration rate-Cockcroft-Gault (r = - 0.50; P = .002 ), glomerular filtration rate-MDRD (r = - 0.59; P < .001 ), and glomerular filtration rate-double plasma sampling method (r = - 0.59; P < .001 ). CONCLUSIONS: Serum cystatin C is an optimal marker of glomerular filtration rate in voluntary kidney donors. PMID- 22309415 TI - Comparison of expanded criteria kidneys with 2-tier standard criteria kidneys: role of delayed graft function in short-term graft outcome. AB - OBJECTIVES: To compare transplant outcomes between expanded criteria donor kidneys and standard criteria donor kidneys. MATERIALS AND METHODS: All adult renal transplants from deceased donors performed in Saudi Arabia over a 24-month period were included. Donor and recipient factors were recorded, and their effects on outcomes with expanded criteria donor and standard criteria donor kidneys were compared. Standard criteria donor kidneys were further subgrouped into optimal and suboptimal groups, and outcomes were compared. RESULTS: A total of 280 deceased-donor kidney transplants were performed during the study period. Of these, 61 (21.8%) involved expanded criteria donor kidneys. Cold ischemia time and prevalence of delayed graft function were similar between expanded criteria and standard criteria kidneys (P = .7 and P = .8). Graft survival rates at 2 years were also similar (93.3% vs 94.6%; P = .8). Delayed graft function exerted a negative effect on 2-year graft survival in both the expanded group (hazard ratio, 4.9; 95% CI 3.2-7.5; P = .001) and the standard group (hazard ratio, 4.6; 95% CI 3.24-7.5; P = .001). No difference was found between the 2 standard criteria subgroups with respect to serum creatinine value at the end of follow-up (P = .8), delayed graft function prevalence (P =.5), or 2-year graft survival (P = .8). The only independent factor affecting graft survival was delayed graft function (P = .001). No independent effect was seen for expanded criteria donor versus standard criteria donor, donor serum creatinine level, or recipient age. CONCLUSIONS: Similar short-term outcomes were found for expanded criteria and standard criteria kidney recipients. Delayed graft function was associated with significant risk of graft loss in both groups, with decreases in 2-year graft survival of 33.3% and 18.3%. No difference was seen between the 2 subtypes of standard criteria donor kidneys. PMID- 22309416 TI - Association between tacrolimus concentration and genetic polymorphisms of CYP3A5 and ABCB1 during the early stage after liver transplant in an Iranian population. AB - OBJECTIVES: Tacrolimus is widely used as an immunosuppressive drug in liver transplant recipients with a narrow therapeutic range and variable individualized pharmacokinetics. Tacrolimus is a substrate of cytochrome P-450 3A enzyme and the drug transporter, P-glycoprotein. MATERIALS AND METHODS: We determined the genotypic frequencies of cytochrome P-4503A5 (rs776746), and ABCB1 (rs1045642), single nucleotide polymorphisms in a population of 100 Iranian liver transplant patients, and investigated the influence of the above-mentioned single nucleotide polymorphisms on tacrolimus concentrations. At 7 and 30 days after transplant, tacrolimus dosages (mg/kg/d), trough blood levels (T0), and dose-adjusted concentrations (concentration/dosage ratio) were determined. Polymerase chain reaction, followed by restriction fragment length polymorphism analysis, was used for genotyping cytochrome P-4503A5*3 [6986A>G] as well as ABCB1 [3435C>T]. RESULTS: Ninety-five percent of the population showed a cytochrome P-4503A5*3/*3 genotype. ABCB13435TT genotype was observed in 33 cases (33%); whereas 51 cases (51%) carried 3435CT, and 16 cases (16%) carried 3435CC. With regard to the ABCB1 and cytochrome P-4503A5, they showed no influence on tacrolimus dosing requirements at 1 week or 1 month after transplant. No association of any genetic variant with the acute rejection rate was found. CONCLUSIONS: Finally, as the liver donor genotype influences tacrolimus pharmacokinetics with regard to expression of cytochrome P-4503A5, far more than the genotype of the recipient; therefore, it should be considered before recommending any personal immunosuppressive treatment based on pharmacogenetics. PMID- 22309417 TI - Long-term outcome of conversion to sirolimus monotherapy after liver transplant. AB - OBJECTIVES: This study sought to assess the long-term efficacy and safety of conversion from a calcineurin inhibitor-based immunosuppressive regimen to sirolimus monotherapy in liver transplant recipients with renal dysfunction. MATERIALS AND METHODS: Twenty-five liver transplant recipients with calcineurin inhibitor-based immunosuppression were included in this single-center, prospective study. Indications were renal dysfunction, avoidance of tumor recurrence, combination renal dysfunction and avoidance of tumor recurrence, and calcineurin inhibitor-related adverse effects. RESULTS: Mean interval between liver transplant and initiation of sirolimus monotherapy was 51.7 months. The mean follow-up was 75.6 months. The mean +/- SD sirolimus whole-blood trough level was 9.0 +/- 2.8 ng/mL after 6 months and 6.0 +/- 1.8 ng/mL after 18 months. No rejection episodes occurred. There was an improvement of the mean creatinine level: 156.1 +/- 54.9 MUmol/L before conversion versus 129.1 +/- 34.7 MUmol/L approximately 3 years after conversion (P < .05). The glomerular filtration rate, measured by technetium Tc-99m-diethylenetriamine penta-acetic aerosol scintigraphy, improved from 27.4 +/- 6.8 mL/min/1.73 m(2) before conversion to 43.3 +/- 6.3 mL/min/1.73 m(2) at final follow-up. Proteinuria increased after conversion to sirolimus after 6 months (P < .05) and at last follow-up. The systolic blood pressure decreased from 151.5 +/- 20.2 to 132.1 +/- 19.4 mm Hg, and the diastolic from 89.7 +/- 11.2 to 82.1 +/- 9.1 mm Hg at last follow-up. Serum cholesterol and serum triglyceride levels were nearly unchanged. However, 50% of the patients were treated with lipid-lowering agents. Four patients had sirolimus-induced adverse effects (thrombocytopenia, gingival hyperplasia, oral ulceration). CONCLUSIONS: Conversion from calcineurin inhibitors to sirolimus monotherapy after liver transplant results in stabilization of renal function in 75% to 85% of cases and of blood pressure, without increased risk of rejection. The spectrum of adverse effects is low. PMID- 22309418 TI - Right-lobe liver transplant from donors with Gilbert syndrome. AB - OBJECTIVES: Donor safety is one of the most important aspects of living-donor liver transplant. The preoperative evaluation of candidates for such transplants essentially starts with serologic and biochemical analyses. However, some potential liver donors with normal liver function test results may have isolated mild hyperbilirubinemia (serum indirect bilirubin level > 20.5 MUmol/L [1.2 mg/dL]). Gilbert syndrome is an autosomal recessive condition that is a common cause of nonhemolytic unconjugated hyperbilirubinemia, and its prevalence is 3% to 10% in the healthy US population. Mild hyperbilirubinemia episodes are expected in people with Gilbert syndrome when they are exposed to physical stress, such as operative intervention or low energy intake. The liver morphologic findings of these individuals are normal; however, there is a debate on the use of people with Gilbert syndrome as living-liver donors. The purpose of this study was to assess the results of right-lobe living-donor hepatectomy of liver donors with Gilbert syndrome. MATERIALS AND METHODS: Between 2004 and 2010, two hundred twenty-five living-donor liver transplants using right-lobe grafts were performed in our hospital. Donors with Gilbert syndrome were defined as those whose serum bilirubin level was greater than 20.5 MUmol/L (1.2 mg/dL). Six of 225 right-lobe living-donor liver transplants were performed using donors with Gilbert syndrome. RESULTS: The median follow-up after transplant was 34 months (range, 18 to 51 mo). One week after the operation, the median bilirubin level for right-lobe liver donors was 34.5 MUmol/L (2.02 mg/dL) (range, 17.1 to 51.3 MUmol/L [1 to 3 mg/dL]), and the median prothrombin time (international normalized ratio) was 1.36 (range, 1.1 to 1.7). The median bilirubin level of the donors after 6 months was 29 MUmol/L (1.7 mg/dL) (range, 20.5 to 41 MUmol/L [1.2 to 2.4 mg/dL]). CONCLUSIONS: Living-donor liver transplant from Gilbert syndrome donors can be safely performed. PMID- 22309419 TI - Nitric oxide synthase in heart and thoracic aorta after liver ischemia and reperfusion injury: an experimental study in rats. AB - OBJECTIVES: We tested the effects of liver reperfusion in the immunohistochemical expression of nitric oxide synthase on the thoracic aorta and the heart. MATERIALS AND METHODS: We randomized 24 male Wistar rats into 3 groups: (1) control; (2) R2 group, with 60 minutes of partial (70%) liver ischemia and 2 hours of global liver reperfusion; (3) and R6 group, with 60 minutes of partial liver ischemia and 6 hours of global liver reperfusion. RESULTS: In the heart, there was little, diffuse immunohistochemical endothelial staining; immunohistochemical inducible nitric oxide synthase staining was expressed in the adventitia layer of intramyocardial vessels in both cases, with a time-dependent but not statistically significant increase. In the thoracic aorta, a time dependent decrease in endothelial nitric oxide synthase expression in the muscular layer after reperfusion, which was statistically significant in R6 versus the control. Positive immunostaining for inducible nitric oxide synthase was seen in the muscular and endothelial layers, and this varied from moderate in the control group, to light in the endothelium in groups R2 and R6. CONCLUSIONS: We observed changes that may be implicated in heart injury and impairment of aortal tone after liver ischemia and reperfusion injury. PMID- 22309420 TI - Protective effects of different combinations of human MCP, DAF, and CD59 on complement-dependent cytolysis in NIH 3T3 cells. AB - OBJECTIVES: To analyze the protective effects against complement-mediated cytolysis of the MCP, DAF, and CD59 human complement regulatory proteins, alone and in combination, on NIH 3T3 mouse fibroblast cells. MATERIALS AND METHODS: We constructed 3 double and 3 single-human complement regulatory protein plasmids (pIRES-hMCP-hDAF, pIRES-hMCP-hCD59, pIRES-hDAF-hCD59, pIRES-A-hMCP, pIRES-B-hDAF, and pIRES-B-hCD59). The plasmids were transfected into NIH 3T3 cells, and stable transfectants were obtained by treatment with 200 kg/m3 G418 for 2 weeks. Normal human serum (50%) as a source of complement was added to the culture medium of stable transfectants. The 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide assay was used to analyze the protective ability of different human complement regulatory protein plasmids on complement-dependent cytolysis. RESULTS: The viability of double-human complement regulatory protein stable transfectants was significantly higher than that of single-human complement regulatory protein stable transfectants (P < .05). Among the double transfectants, cells expressing pIRES-hMCP-hDAF and pIRES-hMCPhCD59 survived better than cells expressing pIREShDAF- hCD59 (91.75% +/- 3.30% and 84.88% +/- 2.36% vs 66.19% +/- 6.52%; P < .05). Among the single transfectants, cells expressing pIRES-A-hMCP or pIRES-B-hDAF survived better than cells expressing pIRES-B-hCD59 or pIRES empty vector (53.76% +/- 3.84% and 56.32% +/- 2.83% vs 43.28% +/- 0.96% and 40.27% +/- 1.11%; P < .05). CONCLUSIONS: These results suggest that the MCP+DAF and MCP+CD59 combinations could be more effective than DAF+CD59 in protecting the NIH 3T3 cells from injury caused by complement dependent cytolysis, whereas MCP or DAF alone is stronger than CD59 alone in inhibiting membrane attack complex formation. PMID- 22309421 TI - Pretransplant nutritional habits and clinical outcome in children undergoing hematopoietic stem cell transplant. AB - OBJECTIVES: This study sought to investigate the effects of pretransplant nutrient content, nutritional status, and nutritional habits on the clinical outcome of children undergoing hematopoietic stem cell transplant. MATERIALS AND METHODS: Forty-one children were enrolled in this study. Dietary assessment was based on a semiquantitative food frequency questionnaire, consisting of 47 food items (including all commonly used prebiotic and probiotic foods in the Turkish cuisine), for the last week before hematopoietic stem cell transplant and a 24 hour dietary recall on admission. RESULTS: Thirteen girls (31.7%) and 28 boys (68.3%) comprised the study group. Of the 41 children, 5 (12.2%) were classified as underweight; 12.2% at risk of being underweight; 53.6% healthy weight; 9.8% overweight; and 12.2% obese. Nutritional status of the children had no effect on the complication rate, duration of febrile neutropenia, and the day of neutrophil and platelet engraftment. Correlation analysis revealed that there was a negative correlation between the day of neutrophil engraftment and the amount of soluble fiber, iron, breast milk, bazlama (a traditional yeast bread), and bulgur consumption. A negative correlation was detected between the number of febrile neutropenia episodes and the amount of yogurt and onion intake. Increased intake of parsley and onion was associated with reduced duration of total parenteral nutrition. The amount of parsley consumption was found to be lower in patients who experienced transplant-related complications. CONCLUSIONS: The nutrient contents and nutritional habits of the patients may affect the course of transplant. It might be recommended that "let them eat yogurt, bazlama, bulgur, onion, and parsley." PMID- 22309422 TI - Successful management of critical illness polyneuropathy and myopathy in renal transplant recipients. AB - Critical illness polyneuropathy and myopathy commonly occur in patients with multiorgan failure and sepsis. Distal muscle weakness and loss of deep tendon reflexes are usually found, with sparing of the cranial nerve musculature. Many risk factors have been identified, specifically hypoxia, hypotension, hyperpyrexia, and age. Other independent risk factors include female sex, severity of illness, duration of organ dysfunction, renal failure and renal replacement therapy, hyperosmolality, parenteral nutrition, low serum albumin level, duration of intensive care unit stay, vasopressor and catecholamine support, and central neurologic failure. Hyperglycemia also has been identified as an independent risk factor, with important potential affect in terms of prevention. Herein, we report the development of critical illness polyneuropathy and myopathy in 7 of 22 renal transplant recipients who underwent successful ventilator weaning during treatment for bronchopneumonia. This is the first report of critical illness polyneuropathy and myopathy among renal transplant recipients. Clinical suspicion and electrophysiologic studies are tools for early diagnosis. Proper management, including correction of risk factors (especially diabetes) and long-term rehabilitation measures might be beneficial. PMID- 22309423 TI - Laparoscopic nephrectomy, ex vivo angioplasty, and renal autotransplant for a renal artery aneurysm: a case report. AB - We describe in this report the case of a renal aneurysm in a 42-year-old woman. The aneurysm measured 27 mm in diameter, and was sited at the first bifurcation of the renal artery. We performed laparoscopic nephrectomy, ex vivo angioplasty and renal autotransplant to avoid ischemic damage to the kidney during reconstruction. The patient recovered and was discharged from the hospital without any complications. Hence, we suggest these treatments can be effectively done in patients with complex renal aneurysms. PMID- 22309424 TI - Kaposi sarcoma of the ureter after liver transplant: case report and literature review. AB - Kaposi sarcoma after an organ transplant is rare and infrequently involves internal organs. There are 2 reported cases in the English literature of Kaposi sarcoma originating from the transplant ureter after kidney transplant. We report a case of Kaposi sarcoma that occurred in the native ureter of the liver transplant recipient. Initially, the patient refused any further investigation and management and 2 years subsequent, had to undergo a left radical nephroureterectomy owing to the loss of renal function and distending pain. He recovered very well and no recurrence was detected at 47 months' follow-up. To our knowledge, it is the first report in English. We review the literature on this topic and explore the therapeutic principles and histologic features of this sarcoma. PMID- 22309425 TI - Is severe electrolyte imbalance a contraindication for heart transplant? AB - Owing to the increasing numbers of patients with end-stage congestive heart failure awaiting heart transplant and the limited number of suitable donor organs, a decrease in stringency of donor criteria has become widely accepted over the last decade. Here, we present a case of a heart donor with severe electrolyte imbalance, specifically severe hypokalemia, and severe hypernatremia. Despite this, heart transplant was a success, and the recipient was discharged from the hospital in good general condition. We recommend further study of this issue with a larger sample size. PMID- 22309426 TI - Autoimmune polyglandular syndrome type II after bone marrow transplant: real transfer or acceleration of a programmed disease? AB - We report a case of autoimmune polyglandular syndrome type II that developed in an 11-year-old boy with homozygous sickle cell disease after allogeneic bone marrow transplant; the donor was his father, who was human leukocyte antigen identical and had vitiligo. On day 24 after transplant, the patient developed grade 1 acute graft-versus-host disease, which was controlled over a period of 3 months with corticosteroid-induced immunosuppression. Full donor engraftment was documented on day 31 after transplant, and this was further confirmed on days 59, 231, 321, 472, 549, and 720. Three months after transplant, the recipient developed adrenal insufficiency, and at 13 months, he developed vitiligo. Seventeen months after transplant, autoimmune thyroid disease, positive for thyroid peroxidase and thyroglobulin autoantibodies, was diagnosed. At the same time, we identified adrenal insufficiency in the donor. We analyzed a serum sample from the recipient for autoantibody markers for type 1 autoimmune diabetes mellitus. The sample was positive for antiglutamic acid decarboxylase. Antibody against 21-hydroxylase enzyme was also found (261 U/mL; normal value, < 1 U/mL). We conclude that the recipient developed autoimmune polyglandular syndrome type II after bone marrow transplant from his father, who was probably affected by the same syndrome. PMID- 22309427 TI - Reaching consensus on the physiotherapeutic management of patients following upper abdominal surgery: a pragmatic approach to interpret equivocal evidence. AB - BACKGROUND: Postoperative pulmonary complications remain the most significant cause of morbidity following open upper abdominal surgery despite advances in perioperative care. However, due to the poor quality primary research uncertainty surrounding the value of prophylactic physiotherapy intervention in the management of patients following abdominal surgery persists. The Delphi process has been proposed as a pragmatic methodology to guide clinical practice when evidence is equivocal. METHODS: The objective was to develop a clinical management algorithm for the post operative management of abdominal surgery patients. Eleven draft algorithm statements extracted from the extant literature by the primary research team were verified and rated by scientist clinicians (n=5) in an electronic three round Delphi process. Algorithm statements which reached a priori defined consensus-semi-interquartile range (SIQR)<0.5-were collated into the algorithm. RESULTS: The five panelists allocated to the abdominal surgery Delphi panel were from Australia, Canada, Sweden, and South Africa. The 11 draft algorithm statements were edited and 5 additional statements were formulated. The panel reached consensus on the rating of all statements. Four statements were rated essential. CONCLUSION: An expert Delphi panel interpreted the equivocal evidence for the physiotherapeutic management of patients following upper abdominal surgery. Through a process of consensus a clinical management algorithm was formulated. This algorithm can now be used by clinicians to guide clinical practice in this population. PMID- 22309428 TI - Ambiguities: residents' experience of 'nursing home as my home'. AB - BACKGROUND: Residential care in nursing homes continues to be necessary for those individuals who are no longer able to live at home. Uncovering what nursing home residents' view as quality of care in nursing homes will help further understanding of how best to provide high quality, person-centred care. AIM: To describe residents' experiences of living in a nursing home related to quality of care. DESIGN: The study utilises a descriptive exploratory design. METHOD: In depth interviews were undertaken with 15 residents who were not cognitively impaired, aged 65 and over and living in one of four nursing homes. The interviews were transcribed verbatim and analysed by categorising of meaning. RESULTS: Residents perceived the nursing home as their home, but at the same time not 'a home'. This essential ambiguity created the tension from which the categories of perceptions of quality emerged. Four main categories of quality of care experience were identified: 'Being at home in a nursing home', 'Paying the price for 24-hour care', 'Personal habits and institutional routines', and 'Meaningful activities for a meaningful day'. CONCLUSIONS: Ambiguities concerning the nursing home as a home and place to live, a social environment in which the residents experience most of their social life and the institution where professional health service is provided were uncovered. High-quality care was when ambiguities were managed well and a home could be created within the institution. Implication for practice. Achieving quality care in nursing homes requires reconciling the ambiguities of the nursing home as a home. This implies helping residents to create a private home distinct from the professional home, allowing residents' personal habits to guide institutional routines and supporting meaningful activities. Using these resident developed quality indicators is an important step in improving nursing home services. PMID- 22309429 TI - Weighted selective collapsing strategy for detecting rare and common variants in genetic association study. AB - BACKGROUND: Genome-wide association studies (GWAS) have been used successfully in detecting associations between common genetic variants and complex diseases. However, common SNPs detected by current GWAS only explain a small proportion of heritable variability. With the development of next-generation sequencing technologies, researchers find more and more evidence to support the role played by rare variants in heritable variability. However, rare and common variants are often studied separately. The objective of this paper is to develop a robust strategy to analyze association between complex traits and genetic regions using both common and rare variants. RESULTS: We propose a weighted selective collapsing strategy for both candidate gene studies and genome-wide association scans. The strategy considers genetic information from both common and rare variants, selectively collapses all variants in a given region by a forward selection procedure, and uses an adaptive weight to favor more likely causal rare variants. Under this strategy, two tests are proposed. One test denoted by BwSC is sensitive to the directions of genetic effects, and it separates the deleterious and protective effects into two components. Another denoted by BwSCd is robust in the directions of genetic effects, and it considers the difference of the two components. In our simulation studies, BwSC achieves a higher power when the casual variants have the same genetic effect, while BwSCd is as powerful as several existing tests when a mixed genetic effect exists. Both of the proposed tests work well with and without the existence of genetic effects from common variants. CONCLUSIONS: Two tests using a weighted selective collapsing strategy provide potentially powerful methods for association studies of sequencing data. The tests have a higher power when both common and rare variants contribute to the heritable variability and the effect of common variants is not strong enough to be detected by traditional methods. Our simulation studies have demonstrated a substantially higher power for both tests in all scenarios regardless whether the common SNPs are associated with the trait or not. PMID- 22309430 TI - Successful treatment of schizophrenia with melperone augmentation in a patient with phenotypic CYP2D6 ultrarapid metabolization: a case report. AB - INTRODUCTION: There are limited treatment options for people with schizophrenia with cytochrome P450 2D6 ultrarapid metabolizer status who do not respond to amisulpride.Furthermore, the literature does not provide evidence-based guidelines for this particular constellation. CASE PRESENTATION: We report the case of a 50-year-old Caucasian female patient with schizophrenia and cytochrome P450 2D6 ultrarapid metabolizer status who experienced an insufficient antipsychotic effect with amisulpride. She was successfully treated with melperone-augmented haloperidol. CONCLUSION: This report yields melperone augmented haloperidol as a possible pharmacological strategy in the described situation. In addition, our observations support the available evidence for the potential of melperone to act as an inhibitor of cytochrome P450 2D6. PMID- 22309432 TI - Tricyclic antidepressant poisoning treated by magnesium sulfate: a randomized, clinical trial. AB - Tricyclic antidepressant (TCA) poisoning is a major problem in medicine, with a high morbidity and mortality rate. The main cause of fatality is cardiac arrhythmias resulting from intoxication. Sodium bicarbonate is the drug of choice, but severe poisoning necessitates further interventions. Magnesium sulfate seems to be effective in this condition. In a randomized, clinical trial, we evaluated all patients with a history of TCA intoxication referred to the Loghman Hakim Hospital Poison Center. The patients were randomly divided into two groups: one treated by bicarbonate infusion (control group) and the other (case group) by the infusion of magnesium sulfate in addition to the treatment in the first group. Seventy-two patients were recruited into the study (36 cases and 36 controls). Mean duration of intensive care unit stay in the cases and controls were 25.63 +/- 9.33 and 82.67 +/- 21.66 hours, respectively (P < 0.001). Mortality rate in the case group was 13.9% and 33.3% in the other group (P = 0.052). Magnesium sulfate can be an effective drug in the treatment of TCA poisoning; however, several randomized, clinical trials are still necessary to confirm this. PMID- 22309433 TI - Preparation of the hybrid film of poly(allylamine hydrochloride)-functionalized graphene oxide and gold nanoparticle and its application for laser-induced desorption/ionization of small molecules. AB - Hybrid films of gold nanoparticles and graphene oxides (GOs) were prepared by directly growing gold nanoparticles on supported thin layers of GO films on a glass slide. The gold/GO nanohybrid films were thoroughly investigated using various analytical methods, including Raman spectroscopy and atomic force microscopy. The hybrid film was then applied to laser desorption/ionization (LDI) of small molecules, which enabled mass spectrometric analysis of analytes. After a series of detailed mechanistic studies and systematic investigations, we found that the gold/GO hybrid films serve as a successful LDI platform for small molecule analysis because of the high desorption efficiency of analytes from the hybrid films without inducing significant fragmentation of analytes. We suggest that the underlying GO films may effectively dissipate excess thermal energy generated by laser irradiation of Au to prevent undesirable analyte fragmentation. PMID- 22309434 TI - Association between changes in quality of life scores and survival in non-small cell lung cancer patients. AB - In patients with advanced cancer, quality of life is as meaningful to patients as the actual length of life. We investigated whether changes in quality of life could predict survival in non-small cell lung cancer. Quality of life was evaluated using EORTC QLQ-C30 (European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire). Cox regression evaluated the prognostic significance of baseline, 3-month and changes in quality of life scores after adjusting for age, gender, treatment history and stage. Two hundred and seventeen patients were men and 213 women. One hundred and fifty-nine patients had stage III while 271 had stage IV disease. Baseline quality of life scales predictive of survival upon multivariate analysis were physical (hazard ratio, 0.90; 95% confidence interval, 0.81-0.98; P= 0.02) and global (hazard ratio, 0.92; 95% confidence interval, 0.87-0.96; P < 0.001). On multivariate analysis, no change variables were significantly predictive of survival. However, in stage IV patients, change in physical function over a period of 3 months showed marginal significance such that every 10-point increase in physical function change score was associated with an 8% decreased risk of death. These findings should be used in clinical practice to systematically address quality of life-related problems of lung cancer patients throughout their treatment course. PMID- 22309435 TI - One hundred years of allergen immunotherapy European Academy of Allergy and Clinical Immunology celebration: review of unanswered questions. AB - Allergen immunotherapy was introduced by Leonard Noon 100 years ago and is the only disease-modifying treatment for allergic individuals. Improved understanding of immunology has taught us a great deal about the underlying mechanisms involved in allergen immunotherapy; however, despite these developments, a number of important questions remain unanswered. Several of these questions relate to the practice of allergen immunotherapy in the clinic, such as: Is it possible to unify units of allergen potency? Which treatment schedules are best? Is allergen immunotherapy effective in all patient groups? Is there a dose-response relationship for efficacy and safety?, and Is there evidence for long-term effects following allergen immunotherapy? Others are related to new developments, such as new indications, or developments in the production of allergens. On the centenary of Noon's discovery, European experts in the field of immunotherapy met in Geneva under the aegis of the EAACI to discuss these controversial issues. This study presents outcomes and conclusions from these discussions. PMID- 22309436 TI - HPLC-DAD-ESI-MS analysis of flavonoid compounds in 5 seedless table grapes grown in Apulian Region. AB - Flavonoids present in skin extracts of red seedless table grape varieties Summer Royal, Autumn Royal, and Crimson, and white seedless varieties Carati and Thompson were analyzed by HPLC-DAD-MS, in 3 y of study (2006 to 2008). The anthocyanins, delphinidin-3-O-glucoside, cyanidin-3-O-glucoside, petunidin-3-O glucoside (with their corresponding p-coumaroyl derivatives), peonidin-3-O glucoside, and malvidin-3-O-glucoside (with their corresponding acetyl, caffeoyl, and p-coumaroyl derivatives) were found. In addition the flavonols quercetin-3-O glucuronide, quercetin-3-O-rutinoside, quercetin-3-O-glucoside, kaempferol-3-O glucoside, kaempferol-3-O-galactoside, and the flavan-3-ols procyanidin B1, procyanidin B2, and catechin were also detected. Anthocyanins were the main flavonoids in red grapes ranging from 24 (Crimson) to 500 (Summer Royal) mg/kg fresh weight of grapes; consistent levels of flavonols and flavan-3-ols were also quantified in all varieties. To determine the effective climatic influence on flavonoids content in field conditions, viticultural practices have been developed, that could exclude the effects of direct solar radiation from confounding the assessment of those related to thermal conditions alone. A strong positive correlation was determined between flavonoids and temperature data that seem to be responsible for the difference of these metabolites along the years; furthermore, it has been possible to define a linear relationship (R(2) = 0.6871, P = 0.0057) between thermal amplitude and total flavonoids values in the red grapes. PRACTICAL APPLICATION: Grapes are economically the most important fruit species in the world and approximately 30% of its production is used as fresh fruit. Because of the very important role of flavonoids in food quality as well as their health-promoting properties, and considering that our experiments were performed along 3 consecutive years, gathered results in this research are quite promising to give a useful information on the flavonoid contents and their evolution in 5 seedless table grapes that are widespread in Mediterranean regions but also in California and South America, and are grown in a viticultural climate (Apulia, South Italy) very close to some regions of Spain, Turkey, Tunisia, and Israel. PMID- 22309437 TI - Folic acid supplementation attenuates high fat diet induced hepatic oxidative stress via regulation of NADPH oxidase. AB - Diets high in saturated fat and cholesterol facilitate weight gain, a predisposing factor that contributes to the onset of obesity and metabolic disorders. Hepatic oxidative stress is commonly reported in various animal models of obesity and has been associated with enhanced expression of NADPH oxidase. We have previously reported several antioxidant mechanisms through which folic acid confers protection during hyperhomocysteinemia-induced oxidative stress. The objective of the present study was to investigate whether folic acid supplementation ameliorates high-fat diet induced oxidative stress in the liver, and to identify the underlying mechanisms. Male C57BL/6J mice were fed a control diet, a high-fat diet, or a high-fat diet supplemented with folic acid for 12 weeks. A high-fat diet led to increased body mass, hepatic lipid peroxidation, and liver injury. There was a significant increase in hepatic NADPH oxidase activity, which was associated with enhanced expression of several NADPH-oxidase subunits. Folic acid supplementation had a protective effect against high-fat diet induced hepatic oxidative stress and liver injury. Further analysis revealed that the antioxidant effect of folic acid was attributed, in part, to transcriptional regulation of NADPH oxidase. These results suggested that folic acid supplementation may be hepatoprotective from liver injury associated with a high-fat diet. PMID- 22309438 TI - Bilateral atypical insufficiency fractures of the proximal tibia and a unilateral distal femoral fracture associated with long-term intravenous bisphosphonate therapy: a case report. AB - INTRODUCTION: Atypical insufficiency fractures of the femur in patients on long term bisphosphonate therapy have been well described in recent literature. The majority of cases are associated with minimal or no trauma and occur in the subtrochanteric or diaphyseal region. CASE PRESENTATION: We describe the case of a 76-year-old British Caucasian woman who presented initially to an emergency department and then to her primary care physician with a long-standing history of bilateral knee pain after minor trauma. Plain radiographs showed subtle linear areas of sclerosis bilaterally in her proximal tibiae. Magnetic resonance imaging confirmed the presence of insufficiency fractures in these areas along with her left distal femur. There are very few reports of atypical insufficiency fractures involving the tibia in patients on long-term bisphosphonate therapy and this appears to be the only documented bilateral case involving the metaphyseal regions of the proximal tibia and distal femur. CONCLUSION: In addition to existing literature describing atypical fractures in the proximal femur and femoral shaft, there is a need for increased awareness that these fractures can also occur in other weight-bearing areas of the skeleton. All clinicians involved in the care of patients taking long-term bisphosphonates need to be aware of the growing association between new onset lower limb pain and atypical insufficiency fractures. PMID- 22309439 TI - The total synthesis and structural revision of stagonolide D. AB - The total synthesis of the putative structure of stagonolide D has been completed. The relative and absolute configuration of stagonolide D was established by synthesizing its optical antipode. The adopted strategy involves the construction of the central macrolide employing ring-closing metathesis (RCM), followed by selective protecting group manipulations and a final concomitant -OTBS deprotection and displacement of an -OMs placed next to it, resulting in the formation of the epoxide ring. PMID- 22309440 TI - Cardiac resynchronization therapy: beyond the heart. PMID- 22309442 TI - Role of distension on duodenal and colonic contractility in mice: a novel myograph for intestines. AB - BACKGROUND: The role of mechanical distension (stretch and tension) on intestinal contractility is poorly understood. METHODS: We introduce a novel isovolumic myograph to quantify the intestinal contractility in response to mechanical stimulation. To evaluate the role of distension on contractility, an external restraint was used to restrict intestinal distension or stretch induced by inflation pressure. The amplitude of intraluminal pressure at isovolumic condition was defined as an index of intestinal contractility. KEY RESULTS: The in situ maximal contraction (1.42 +/- 0.39 mmHg) of duodenum in response to inflation pressure was similar to the in vitro maximal contraction (1.39 +/- 0.37 mmHg). As the pressure was increased, the in situ duodenal contraction attenuated faster than the in vitro one. The in situ maximal contraction (4.86 +/- 1.32 mmHg) of distal colon in response to inflation pressure was significantly larger than the in vitro maximal contraction (2.31 +/- 0.67 mmHg). With increase of pressure, the in situ colonic contractility (1.82 +/- 0.87 mmHg) became similar to the in vitro counterpart (1.61 +/- 0.98 mmHg). With restraint, the maximal contraction of duodenum and distal colon decreased from 4.86 +/- 1.32 and 1.42 +/ 0.39 mmHg to 2.91 +/- 0.87 and 0.97 +/- 0.29 mmHg, respectively. Finally, a significant linear relation was found between strain and amplitude of contraction for both duodenum and colon which became non-significant with restraint. CONCLUSIONS & INFERENCES: Our results suggest that distension is an important stimulus for intestinal contractility and nervous regulation is implicated in the intestinal contractility response to mechanical stimulus. PMID- 22309443 TI - Comparison of the performance of DBA/2 and C57BL/6 mice in transitive inference and foreground and background contextual fear conditioning. AB - DBA/2 mice have altered hippocampal structure and perform poorly in several hippocampus-dependent contextual/spatial learning tasks. The performance of this strain in higher cognitive tasks is less studied. Transitive inference is a hippocampus-dependent task that requires an abstraction to be made from prior rules to form a new decision matrix; performance of DBA/2 mice in this task is unknown, whereas contextual fear conditioning is a hippocampus-dependent task in which DBA/2 mice have deficits. The present study compared DBA/2J and C57BL/6J inbred mice in two different contextual fear conditioning paradigms and transitive inference to test whether similar deficits are seen across these hippocampus-dependent tasks. For background fear conditioning, mice were trained with two paired presentations of an auditory conditioned stimulus (CS, 30 seconds, 85 dB white noise) paired with an unconditioned stimulus (US, 2 seconds, 0.57 mA footshock), the context was a continuous background CS. Mice were tested for contextual learning 24 hours later. Foreground fear conditioning differed in that no auditory CS was presented. For transitive inference, separate mice were trained to acquire a series of overlapping odor discrimination problems and tested with novel odor pairings that either did or did not require the use of transitive inference. DBA/2 mice performed significantly worse than the C57BL/6 in both foreground and background fear conditioning and transitive inference. These results demonstrate that the DBA/2 mice have deficits in higher-cognitive processes and suggest that similar substrates may underlie deficits in contextual learning and transitive inference. PMID- 22309444 TI - Pure-tone auditory thresholds are not chronically elevated in multiple sclerosis. AB - Despite the fact that acute cases of multiple sclerosis (MS)-related pure-tone hearing loss have been reported in the literature, consensus is lacking as to the chronic influences of MS on pure-tone thresholds. Most studies examining such influences have been limited by small sample sizes, lack of statistical comparisons between patients and controls, and confounding of the hearing measure with influences from sex and age. To date, associations between pure-tone thresholds and central MS-related brain lesions have not been assessed. In this study, pure-tone thresholds ranging from 0.5 to 8 kHz were measured in 73 MS patients and 73 individually age- and gender-matched normal controls. In 63 MS patients, correlations were computed between the threshold values and MRI determined lesion activity in 26 central brain regions. Although thresholds were strongly influenced by sex, age, and tonal frequency, no meaningful influences of MS were discerned. Moreover, no significant association between the threshold values and central MS-related lesion activity was evident in any brain region evaluated. This study, the largest on this topic to use carefully matched control subjects and the sole study to assess relationships between auditory thresholds and central MS-related lesions, strongly suggests that (a) MS is not chronically associated with pure-tone hearing loss and (b) pure-tone thresholds are unrelated to MS lesion activity in higher brain regions. These findings, along with general reports from the literature, support the concept that when MS-related hearing threshold deficits are found, they are episodic and primarily dependent on lesions within the eighth nerve or brainstem. PMID- 22309445 TI - Mutational ataxia resulting from abnormal vestibular acquisition and processing is partially compensated for. AB - Due to the multisensory input into the balance system, the loss of one input, such as an ear, can generally be compensated for. However, when a mismatch or incomplete loss of inputs occurs, the ability to compensate for the stimulus misrepresentation may be compromised. The inner ear and cerebellum are important input and processing centers for balance but no genetic models have been generated to assess balance or compensation in the abnormal development of both these organs/brain areas. Important to their formation is regulation of proliferation mediated by the proto-oncogene N-Myc. Conditional knockouts (CKOs) of N-Myc using Tg(Pax2-Cre) have a misshapen and smaller ear with a fused utricle, saccule, and cochlea and absent horizontal canal, aberrant cochlear and vestibular innervations, and a size reduction in the cerebellum. CKOs are viable with obvious behavioral deficits, including circling behavior and unstable gait. To test the degree of ataxia and possible compensation of vestibular defects in these mutant mice, we use the Noldus Catwalk System to assess the gait of Tg(Pax2 Cre) N-Myc CKOs over five months. N-Myc CKOs perform worse than control littermates, in particular, in step regularity. We show that disrupting one member of the Myc family during embryonic development coincides with a differential loss of function in the cochlea compared to the vestibular apparatus. In addition, we show that the distortion in the ear morphology combined with a reduction of the cerebellum, rather than a complete loss of the vestibular-cerebellar pathway, leads to partial behavioral compensation that remains unchanged over time. PMID- 22309446 TI - Nicotine normalizes event related potentials in COMT-Val-tg mice and increases gamma and theta spectral density. AB - Regulation of dopamine neurotransmission is essential for cognitive processes. In humans and rodents, the relationship between dopamine signaling and cognitive performance is described as a dose-dependent, inverted-U curve whereby excess or insufficiency of dopamine in prefrontal cortex has detrimental effects. Previous studies have indicated that prefrontal dopamine levels are associated with genetic variation in catechol-O-methyltransferase (COMT), a regulatory enzyme that controls dopamine availability. Furthermore, smokers who carry the high activity COMT-Val allele are more prone to cognitive deficits and have an increased risk of smoking relapse. The present study employed transgenic mice expressing the human COMT-Val variant to determine the effects of the high activity COMT allele on electrophysiological markers, including the P20, N40, and P80 components of the auditory event-related potential, as well as baseline and auditory event-related power and phase-synchrony in theta and gamma ranges. We also examined the effects of nicotine on these measures to investigate the potential effects of smoking on COMT-mediated electrophysiological activity. COMT Val-tg mice displayed increased N40 latency and decreased P80 amplitude as well as reduced baseline theta and gamma power. Nicotine increased P20 and P80 amplitudes, decreased N40 amplitude, increased P20 and N40 latencies, and reduced P80 latency. Nicotine also increased the event-related power and phase synchrony, yielding an increase in signal-to-noise ratio across theta and gamma ranges. COMT activity specifically alters long-latency components of the event-related response. Nicotine restored normal event-related activity among COMT-Val-tg mice, suggesting one mechanism through which nicotine may normalize cognitive function among people with the high-activity allele. PMID- 22309447 TI - Process of implementation and development of early psychosis clinical services in Italy: a survey. AB - AIM: To carry out an in-depth survey into the method of providing early intervention in schizophrenia in Italy and to evaluate the process of development of early psychosis clinical services following the pilot programme 'Programma 2000' and the publishing of Italian National Guidelines. METHODS: Topic-specific national and international clinical and research programmes, alongside national guidelines, were taken into consideration in order to create an ad hoc questionnaire. A telephone survey using this questionnaire was carried out. A randomized sample of 152 mental health centres (MHCs) were involved, equal to 21.5% of all Italian MHCs. RESULTS: The process of nationwide diffusion of early psychosis clinical services in Italy is frustratingly slow. Italian MHCs, including a specialized service for early interventions in schizophrenia, are estimated at being between 20% and 30%. Most services adopt a generalist approach and more frequently follow guidelines drawn up within the centres than Italian National Guidelines, involve few patients and provide a high variability of treatment options. The distribution of these services in Italy is not homogenous and influenced by demographic factors. CONCLUSION: Our data are consistent with worldwide literature showing a slow and variable implementation of early psychosis services in all nations. The main efforts to make these services diffused should be addressed to favour the process of localized adaptation to the guidelines, to demand possible and realistic implementation of the standard method, to stimulate policy endorsement and resources' allocation, and to particularly support the rural and the poorer zones. PMID- 22309448 TI - Investigation of the male pattern baldness major genetic susceptibility loci AR/EDA2R and 20p11 in female pattern hair loss. AB - BACKGROUND: The aetiology of female pattern hair loss (FPHL) is largely unknown. However, it is hypothesized that FPHL and male pattern baldness (AGA) share common susceptibility alleles. The two major susceptibility loci for AGA are the androgen receptor (AR)/ectodysplasin A2 receptor (EDA2R) locus on the X chromosome, and a locus on chromosome 20p11, for which no candidate gene has yet been identified. OBJECTIVES: To examine the role of the AR/EDA2R and 20p11 loci in the development of FPHL using 145 U.K. and 85 German patients with FPHL, 179 U.K. supercontrols and 150 German blood donors. METHODS: Patients and controls were genotyped for 25 single nucleotide polymorphisms (SNPs) at the AR/EDA2R locus and five SNPs at the 20p11 locus. RESULTS: Analysis of the AR/EDA2R locus revealed no significant association in the German sample. However, a nominally significant association for a single SNP (rs1397631) was found in the U.K. sample. Subgroup analysis of the U.K. patients revealed significant association for seven markers in patients with an early onset (P = 0.047 after adjustment for the testing of multiple SNPs by Monte Carlo simulation). No significant association was obtained for the five 20p11 variants, either in the overall samples or in the analysis of subgroups. CONCLUSIONS: The observed association suggests that the AR/EDA2R locus confers susceptibility to early-onset FHPL. Our results do not implicate the 20p11 locus in the aetiology of FPHL. PMID- 22309449 TI - Sustained-release alginate-chitosan pellets prepared by melt pelletization technique. AB - CONTEXT: Alginate-chitosan pellets prepared by extrusion-spheronization technique exhibited fast drug dissolution. OBJECTIVE: This study aimed to design sustained release alginate pellets through rapid in situ matrix coacervation by chitosan during dissolution. METHODS: Pellets made of alginate with chitosan and/or calcium acetate were prepared using solvent-free melt pelletization technique which prevented reaction between processing materials during agglomeration and allowed such reaction to occur only in dissolution phase. RESULTS: Drug release was retarded in pH 2.2 medium when pellets were formulated with calcium acetate or chitosan till a change in medium pH to 6.8. The sustained-release characteristics of calcium alginate pellets were attributed to pellet dispersion and rapid cross-linking by soluble Ca(2+) during dissolution. The slow drug release characteristics of alginate-chitosan pellets were attributed to polyelectrolyte complexation and pellet aggregation into swollen structures with reduced erosion. The drug release was, however, not retarded when both calcium acetate and chitosan coexisted in the same matrix as a result of chitosan shielding of Ca(2+) to initiate alginate cross-linkages and rapid in situ solvation of calcium acetate induced fast pellet dispersion and chitosan losses from matrix. CONCLUSION: Similar to calcium alginate pellets, alginate-chitosan pellets demonstrated sustained drug release property though via different mechanisms. Combination of alginate, chitosan and calcium acetate in the same matrix nevertheless failed to retard drug release via complementary drug release pattern. PMID- 22309450 TI - Medicago truncatula transporter database: a comprehensive database resource for M. truncatula transporters. AB - BACKGROUND: Medicago truncatula has been chosen as a model species for genomic studies. It is closely related to an important legume, alfalfa. Transporters are a large group of membrane-spanning proteins. They deliver essential nutrients, eject waste products, and assist the cell in sensing environmental conditions by forming a complex system of pumps and channels. Although studies have effectively characterized individual M. truncatula transporters in several databases, until now there has been no available systematic database that includes all transporters in M. truncatula. DESCRIPTION: The M. truncatula transporter database (MTDB) contains comprehensive information on the transporters in M. truncatula. Based on the TransportTP method, we have presented a novel prediction pipeline. A total of 3,665 putative transporters have been annotated based on International Medicago Genome Annotated Group (IMGAG) V3.5 V3 and the M. truncatula Gene Index (MTGI) V10.0 releases and assigned to 162 families according to the transporter classification system. These families were further classified into seven types according to their transport mode and energy coupling mechanism. Extensive annotations referring to each protein were generated, including basic protein function, expressed sequence tag (EST) mapping, genome locus, three-dimensional template prediction, transmembrane segment, and domain annotation. A chromosome distribution map and text-based Basic Local Alignment Search Tools were also created. In addition, we have provided a way to explore the expression of putative M. truncatula transporter genes under stress treatments. CONCLUSIONS: In summary, the MTDB enables the exploration and comparative analysis of putative transporters in M. truncatula. A user-friendly web interface and regular updates make MTDB valuable to researchers in related fields. The MTDB is freely available now to all users at http://bioinformatics.cau.edu.cn/MtTransporter/. PMID- 22309451 TI - Development of a novel adsorptive membrane chromatographic method for the fractionation of polyphenols from bilberry. AB - A novel membrane chromatographic method with a membrane adsorber (Sartobind S) has been developed on the laboratory scale that allows a fractionation of bilberry (Vaccinium myrtillus) constituents into the following three groups of polyphenols: anthocyanins, copigments, and polymers. By using this methodology, a pure anthocyanin fraction free of other copigments and polymeric phenols can be obtained. Using this approach, it provides fractions allowing a more thorough testing of the biological effects of the individual groups of bilberry polyphenols as well as the study of possible synergistic effects between these different groups of bioactive constituents from bilberry. PMID- 22309452 TI - Cardiovascular magnetic resonance by non contrast T1-mapping allows assessment of severity of injury in acute myocardial infarction. AB - BACKGROUND: Current cardiovascular magnetic resonance (CMR) methods, such as late gadolinium enhancement (LGE) and oedema imaging (T2W) used to depict myocardial ischemia, have limitations. Novel quantitative T1-mapping techniques have the potential to further characterize the components of ischemic injury. In patients with myocardial infarction (MI) we sought to investigate whether state-of the art pre-contrast T1-mapping (1) detects acute myocardial injury, (2) allows for quantification of the severity of damage when compared to standard techniques such as LGE and T2W, and (3) has the ability to predict long term functional recovery. METHODS: 3T CMR including T2W, T1-mapping and LGE was performed in 41 patients [of these, 78% were ST elevation MI (STEMI)] with acute MI at 12-48 hour after chest pain onset and at 6 months (6M). Patients with STEMI underwent primary PCI prior to CMR. Assessment of acute regional wall motion abnormalities, acute segmental damaged fraction by T2W and LGE and mean segmental T1 values was performed on matching short axis slices. LGE and improvement in regional wall motion at 6M were also obtained. RESULTS: We found that the variability of T1 measurements was significantly lower compared to T2W and that, while the diagnostic performance of acute T1-mapping for detecting myocardial injury was at least as good as that of T2W-CMR in STEMI patients, it was superior to T2W imaging in NSTEMI. There was a significant relationship between the segmental damaged fraction assessed by either by LGE or T2W, and mean segmental T1 values (P < 0.01). The index of salvaged myocardium derived by acute T1-mapping and 6M LGE was not different to the one derived from T2W (P = 0.88). Furthermore, the likelihood of improvement of segmental function at 6M decreased progressively as acute T1 values increased (P < 0.0004). CONCLUSIONS: In acute MI, pre-contrast T1 mapping allows assessment of the extent of myocardial damage. T1-mapping might become an important complementary technique to LGE and T2W for identification of reversible myocardial injury and prediction of functional recovery in acute MI. PMID- 22309453 TI - SapB and the rodlins are required for development of Streptomyces coelicolor in high osmolarity media. AB - Streptomyces coelicolor produces spore-forming aerial hyphae after a period of vegetative growth. These aerial structures are decorated with a hydrophobic coating of rodlets consisting of chaplins and rodlins. Here, we show that rodlins and the surface-active peptide SapB are essential for development during growth in a medium with high osmolarity. To this end, both vegetative and aerial hyphae secrete SapB, whereas rodlins are only secreted by the spore-forming aerial hyphae. PMID- 22309454 TI - An optimum time for intravenous cannulation after induction with sevoflurane in children. AB - BACKGROUND: It is a common practice to perform inhalational induction with sevoflurane followed by intravenous cannulation in children. However, there is little information regarding the time at which the intravenous cannulation can be attempted safely after sevoflurane induction. AIM: To determine the optimal time for safe intravenous cannulation in children induced with sevoflurane. METHODS: Pediatric patients aged 4-10 years receiving sevoflurane inhalational induction for elective cases were recruited. General anesthesia was induced with sevoflurane and oxygen via mask, then intravenous cannulation was attempted. The time for intravenous cannulation was determined by the use of up-and-down method using 30 s as a step size. Intravenous cannulation without any movement, coughing, or laryngospasm was considered successful. The up-and-down sequences were analyzed by the probit test. RESULTS: The time for effective intravenous cannulation in 50% patients was 1.90 min (95% confidence limits, 1.24-2.41 min). The time for effective cannulation in 95% of patient population was 3.32 min (95% confidence limits, 2.68-6.77 min). CONCLUSION: We recommend an optimal time of 3.5 min for attempting intravenous cannulation after the loss of eyelash reflex with sevoflurane induction. PMID- 22309455 TI - An epigenetic approach to pancreatic cancer treatment: the prospective role of histone deacetylase inhibitors. AB - Pancreatic ductal adenocarcinoma (PDAC) is quite resistant to conventional treatments, and gemcitabine, the standard chemotherapeutic agent, offers only a small benefit. Development and progression of PDAC are complex processes involving dysregulation of multiple signal transduction pathways arising from not only genetic but also epigenetic alterations. This makes the epigenetic approach to the treatment of PDAC of great interest. Histone deacetylases, a family of enzymes that, by removal of acetyl groups from a variety of histone and nonhistone proteins, play an important role in the epigenetic regulation of gene expression, are frequently dysregulated in PDAC. In particular, overexpression of class I histone deacetylases has been related to higher tumor grade, poor prognosis and development of chemoresistance. Histone deacetylase inhibitors (HDACIs), a novel class of agents endowed with pleiotropic antitumor effects, appear promising either for their preferential toxicity towards transformed as compared to normal cells and their ability to synergistically enhance the anticancer activity of radiotherapy and many chemotherapeutic agents. Many HDACIs have been shown to increase the antiproliferative and proapoptotic effects of gemcitabine, 5-fluorouracil and bortezomib, a new proteasome inhibitor, in vitro and in vivo PDAC xenograft models. MGCD0103, romidepsin, panobinostat, vorinostat and valproic acid, are currently being tested in association with radiotherapy or chemotherapy (gemcitabine, fluoropyrimidines, proteasome inhibitors) in phase I II clinical trials in patients with locally advanced or metastatic PDAC. PMID- 22309456 TI - Screening mammography beliefs and recommendations: a web-based survey of primary care physicians. AB - BACKGROUND: The appropriateness and cost-effectiveness of screening mammography (SM) for women younger than 50 and older than 74 years is debated in the clinical research community, among health care providers, and by the American public. This study explored primary care physicians' (PCPs) perceptions of the influence of clinical practice guidelines for SM; the recommendations for SM in response to hypothetical case scenarios; and the factors associated with perceived SM effectiveness and recommendations in the US from June to December 2009 before the United States Preventive Services Task Force (USPSTF) recently revised guidelines. METHODS: A nationally representative sample of 11,922 PCPs was surveyed using a web-based questionnaire. The response rate was 5.7% (684); (41%) 271 family physicians (FP), (36%) 232 general internal medicine physicians (IM), (23%) 150 obstetrician-gynaecologists (OBG), and (0.2%) 31 others. Cross sectional analysis examined PCPs perceived effectiveness of SM, and recommendation for SM in response to hypothetical case scenarios. PCPs responses were measured using 4-5 point adjectival scales. Differences in perceived effectiveness and recommendations for SM were examined after adjusting for PCPs specialty, race/ethnicity, and the US region. RESULTS: Compared to IM and FP, OBG considered SM more effective in reducing breast cancer mortality among women aged 40-49 years (p = 0.003). Physicians consistently recommended mammography to women aged 50-69 years with no differences by specialty (p = 0.11). However, 94% of OBG "always recommended" SM to younger and 86% of older women compared to 81% and 67% for IM and 84% and 59% for FP respectively (p = < .001). In ordinal regression analysis, OBG specialty was a significant predictor for perceived higher SM effectiveness and recommendations for younger and older women. In evaluating hypothetical scenarios, overall PCPs would recommend SM for the 80 year woman with CHF with a significant variation by specialty (38% of OBG, 18% of FP, 17% of IM; p = < .001). CONCLUSIONS: A majority of physicians, especially OBG, favour aggressive breast cancer screening for women from 40 through 79 years of age, including women with short life expectancy. Policy interventions should focus on educating providers to provide tailored recommendations for mammography based on individualized cancer risk, health status, and preferences. PMID- 22309457 TI - Thermographic imaging during nasal peanut challenge may be useful in the diagnosis of peanut allergy. AB - BACKGROUND: Double-blinded challenges are widely used for diagnosing food allergy but are time-consuming and cause severe reactions. Outcome relies on subjective interpretation of symptoms, which leads to variations in outcome between observers. Facial thermography combined with nasal peanut challenge was evaluated as a novel objective indicator of clinical allergy. METHODS: Sixteen children with positive blinded peanut challenge underwent nasal challenge with 10 MUg peanut protein or placebo. Mean skin temperatures were recorded from the mouth and nose using infrared thermography over 18 min. RESULTS: The area under curve of nasal skin temperature was significantly elevated after peanut vs placebo (18.2 vs 4.8 degrees Cmin). The maximum increase in temperature was also significantly greater after peanut: mean difference +0.9 degrees C. CONCLUSION: This feasibility study shows thermography can detect inflammation caused by nasal challenges whilst employing one thousand-fold less peanut than an oral challenge. This novel technique could be developed to provide a rapid, safe and objective clinical allergy test. PMID- 22309458 TI - A refractory case of chromoblastomycosis due to Fonsecaea monophora with improvement by photodynamic therapy. AB - Chromoblastomycosis is one of the most frequently encountered mycoses in tropical and temperate regions caused by the implantation of the infectious structures and one which is associated with low cure and high relapse rates. The etiologic agents play a critical role affecting clinical outcome and in southern China, Fonsecaea pedrosoi and F. monophora are the main causative agents of chromoblastomycosis. We treated, for two years, a 55-year-old male patient with chromoblastomycosis caused by F. monophora with itraconazole and terbinafine, two antifungals recommend in earlier papers in the literature but without any positive response. As a result we introduced the photodynamic therapy (PDT) employing 5-aminolevulinic acid (ALA) irradiation. The lesions were improved after two periods of ALA-PDT treatment, each consisting of exposures at weekly intervals for 5 weeks but new lesions developed with the cessation of ALA-PDT treatment. Thereafter, positive clinical improvement was obtained when voriconazole at 200 mg was combined with terbinafine at 250 mg in treating the patient. The in vitro susceptibility of the F. monophora isolate to terbinafine, itraconazole, and voriconazole was assessed and the fungus was found to be sensitive to all three, with the minimal inhibitory concentrations of 0.125, 1, 0.0625 MUg/ml, respectively. However, the determination of in vitro susceptibility profiles may not predict clinical response. PMID- 22309459 TI - Treatment of severe forms of paracoccidioidomycosis: is there a role for corticosteroids? AB - Despite their immunosuppressive effects, corticosteroids have long been used as adjunct therapy (aCST) in the treatment of infectious diseases. The rationale is that in certain infections it is necessary to decrease the exacerbated host's inflammatory response, which can otherwise result in tissue damage and organ dysfunction. In fact, a major concern in treating paracoccidioidomycosis (PCM) is the host's intense inflammatory response to Paracoccidioides brasiliensis, which can be further intensified by antifungal therapy. Depending on its localization, this immunological phenomenon may be life threatening or result in permanent sequels, as is the case for some patients with cerebral or laryngeal involvement. However, the literature on aCST in paracoccidioidomycosis treatment is scarce and as a result we present our recent experience in the management of four patients with severe PCM manifestations, i.e., cerebral paracoccidioidal granuloma, laryngeal stenosis, compressive abdominal mass, and exacerbated inflammatory response with tissue destruction. In addition to the antifungal therapy, these patients required aCST, which probably promoted their clinical improvement and/or prevented serious complications. We suggest that aCST: (a) can potentially help in the management of selected cases of severe forms of PCM, particularly when there is a risk of acute complications, and (b) that it can be used safely provided that the risk-benefit ratio is carefully weighed. Well-controlled, prospective studies of aCST in the treatment of severe cases of paracoccidioidomycosis are needed to better define its role in the management of PCM. PMID- 22309460 TI - Cortical morphometry in narcolepsy with cataplexy. AB - The sleep-wake disorder narcolepsy with cataplexy is associated with the loss of hypocretin-(orexin-) producing neurons in the lateral hypothalamus. Several studies have reported abnormal cerebral activation in patients with narcolepsy with cataplexy. It remains unclear, however, whether these functional changes are related to structural alterations, particularly at the cortical level. To quantify structural brain changes associated with narcolepsy with cataplexy, we used high-resolution T1-weighted magnetic resonance imaging (MRI) in 12 patients compared with 12 healthy participants matched for age and gender. Subcortical and regional cortical volumes were measured using a method unbiased by non-linear registration. Further whole-brain analyses were conducted, measuring cortical characteristics, such as cortical thickness and gyrification, at thousands of points across each hemisphere using validated algorithms. Statistical analyses accounted for an effect of age and gender. We observed decreased cortical volume in the left paracentral lobule and increased cortical volume in the left caudal part of the middle frontal gyrus in narcoleptic patients compared with controls. Cortical thickness in prefrontal areas was inversely correlated with the severity of narcolepsy. Further, we observed several clusters of cortical thinning in patients with childhood or adolescent onset of narcolepsy compared with patients with adult onset of the disease. Our results suggest that specific anatomical changes may differentiate subgroups of narcolepsy patients with different clinical profiles (such as varying symptom severity or different age at onset). Future studies with larger groups of sleepy patients are required to assess whether distinct patterns of anatomical changes may distinguish narcolepsy from non-hypocretin-deficient hypersomnia disorders. PMID- 22309461 TI - Comparison of oxidized and reduced glutathione in the bread-making qualities of rice batter. AB - The demand for gluten-free bread is growing as the recognition of celiac disease and wheat allergy has increased worldwide. In our previous study, reduced glutathione (GSH) was found to improve the gas-retaining properties of rice batter used for gluten-free bread. In this article, oxidized glutathione (GSSG) was shown to have the same effect. Moreover, sensory tests revealed that GSSG bread had a significantly reduced sulfurous odor. Analyses by a gas chromatography-flame photometric detector demonstrated the presence of hydrogen sulfide and methyl mercaptan in the headspace of GSH bread, and also their significant reduction in GSSG bread. The viscoelastic properties and microstructures of GSSG and GSH bread did not noticeably differ. These observations suggest the usefulness of GSSG in making gluten-free rice bread and extend our knowledge of the use of glutathione in food processing. Practical Application: Glutathione, a widely-distributed peptide in cells, improves the bread-making quality of gluten-free rice batter. While both the reduced (GSH) and oxidized (GSSG) glutathione are effective, GSSG-bread has significantly reduced sulfurous odor compared to GSH-bread. PMID- 22309463 TI - Cardiac pacemakers in electric and magnetic fields of 400-kV power lines. AB - BACKGROUND: The cardiac pacemaker (PM) implantation rate per million is high. Earlier studies have found interference to PMs by electromagnetic fields. The aim of the study is to investigate disturbances in cardiac PM using a human-shaped phantom in electric and magnetic fields of 400-kV power lines. METHODS: The phantom was used in the following manner: isolated from the ground, grounded from left or right foot, or grounded from left or right hand. RESULTS: Out of the tested PMs one had such a disturbance that it set the pace 60 times per minute, when the electric field was 6.7-7.5 kV/m and the magnetic field was 2.4-2.9 MUT. The electrode configuration of the PM was unipolar. In bipolar configuration, the same PM had no disturbance. During the test period, other PMs only had minor disturbances or none at all. Some PMs do not record time information for minor disturbances. In such cases, it was impossible to link the disturbances to the exposure under the power line. CONCLUSIONS: The electric field under a 400-kV power line may disturb a PM. However, only one type out of several tested PMs showed a major disturbance and that was only with a unipolar electrode configuration. The risk of disturbances is therefore not deemed to be high. PMID- 22309464 TI - Clinical differences between early- and late-onset social anxiety disorders. AB - AIM: The aim of this study was to elucidate the clinical differences between early- and late-onset social anxiety disorder (SAD) in the Korean population. METHODS: Three hundred and eighty-seven outpatients diagnosed with SAD participated in this study. Confirmation of SAD diagnosis was based on the Mini International Neuropsychiatric Interview. All subjects completed the Liebowitz Social Anxiety Scale and anxiety-trait-related scales such as the Anxiety Sensitivity Index, Retrospective Self-Report of Inhibition, Trait Form of the State-Trait Anxiety Inventory, and Beck Depression Inventory. RESULTS: The early onset group (n = 209) consisted of subjects aged up to 18 years at the time of onset, whereas the late-onset group (n = 178) consisted of subjects older than 18 years at the time of onset. Early-onset SAD patients were more likely to have the generalized subtype and to visit clinics with chief complaints other than social anxiety symptoms. They exhibited more severe symptoms and higher behavioural inhibitions. After adjusting for age and symptom severity, behavioural inhibition was the only significant difference between the two groups. The degree of behavioural inhibitions was associated with earlier onset age. CONCLUSION: Symptom severity and behavioural inhibitions, especially in social/school situations, were clinical characteristics that differentiated between early- and late-onset SAD. PMID- 22309465 TI - Sudden hearing loss and pregnancy: a review. AB - BACKGROUND: Acute hearing loss is a distressing albeit rare occurrence in pregnancy. Due to its infrequent presentation, little is known of its cause, and the best management is unclear. OBJECTIVE: To present a summary of current knowledge regarding sudden hearing loss in pregnancy and its management, by reviewing the published literature. DATA SOURCES: The following electronic databases: PubMed (MEDLINE), Ovid (MEDLINE), all EBM Reviews (Cochrane DSR, ACP Journal Club, DARE and CCTR) and Embase; plus a hand search of reference lists of retrieved papers. STUDY SELECTION AND DATA EXTRACTION: All papers retrieved using key word searches for 'sudden hearing loss and pregnancy' and 'sudden deafness and pregnancy' were reviewed. Due to the scarcity of literature, all studies identified were included in this review. DATA SYNTHESIS AND CONCLUSIONS: All retrieved papers were reviewed. Sudden hearing loss is a rare occurrence during pregnancy, leading to a dearth of literature due to limited clinical experience. Audiological investigation findings for such patients remain equivocal. Recovery can be spontaneous during the postpartum period. In patients who require medical treatment, a dextran 40 infusion can be employed. There remains scope for further research, in the form of larger studies, to ascertain the best management option for this clinical problem. PMID- 22309466 TI - In vivo dynamic imaging of intestinal motions using diet-related autofluorescence. AB - BACKGROUND: Tissue background autofluorescence induced by standard murine diets containing chlorophyll is a significant problem for fluorescence whole-body imaging. However, as red chlorophyll autofluorescence delineates the gastrointestinal (GI) tract in the abdomen of the mouse, it should be possible to dynamically and non-invasively image intestinal motions. Herein, we non invasively imaged for the first time intestinal motions, such as peristaltic and segmental motions, without an exogenous imaging agent, using red chlorophyll fluorescence. METHODS: Mice were illuminated with 660-nm light from a laser diode and autofluorescence at 710 nm was acquired dynamically for 5 min with 200-ms exposure time. Fluorescent imaging data were analyzed to generate a three dimensional spatiotemporal map to quantitate intestinal motions. KEY RESULTS: Peristaltic and segmental motions were observed in vivo in mice. Our quantification showed that the frequency and propagation velocity of peristaltic contractile waves in the small intestine were measured to be 28.6 cycles per min and 1.82 +/- 0.56 cm s(-1), respectively. CONCLUSIONS & INFERENCES: This simple, but unexplored imaging technique can provide a means to monitor intestinal motility disorders and response to therapeutic agents. PMID- 22309467 TI - Histidine-catalyzed asymmetric aldol addition of enolizable aldehydes: insights into its mechanism. AB - Extensive studies of asymmetric cross-aldol addition between enolizable aldehydes are described and provide a deeper insight into histidine-catalyzed aldol additions. In particular, aspects of enantio- as well as diastereoselectivity of these reactions are discussed. Rules and predictions of configurative outcome are explained by using different transition-state models. These discussions are confirmed by extensive computations. PMID- 22309468 TI - Ac/Ds-transposon activation tagging in poplar: a powerful tool for gene discovery. AB - BACKGROUND: Rapid improvements in the development of new sequencing technologies have led to the availability of genome sequences of more than 300 organisms today. Thanks to bioinformatic analyses, prediction of gene models and protein coding transcripts has become feasible. Various reverse and forward genetics strategies have been followed to determine the functions of these gene models and regulatory sequences. Using T-DNA or transposons as tags, significant progress has been made by using "Knock-in" approaches ("gain-of-function" or "activation tagging") in different plant species but not in perennial plants species, e.g. long-lived trees. Here, large scale gene tagging resources are still lacking. RESULTS: We describe the first application of an inducible transposon-based activation tagging system for a perennial plant species, as example a poplar hybrid (P. tremula L. * P. tremuloides Michx.). Four activation-tagged populations comprising a total of 12,083 individuals derived from 23 independent "Activation Tagging Ds" (ATDs) transgenic lines were produced and phenotyped. To date, 29 putative variants have been isolated and new ATDs genomic positions were successfully determined for 24 of those. Sequences obtained were blasted against the publicly available genome sequence of P. trichocarpa v2.0 (Phytozome v7.0; http://www.phytozome.net/poplar) revealing possible transcripts for 17 variants.In a second approach, 300 randomly selected individuals without any obvious phenotypic alterations were screened for ATDs excision. For one third of those transposition of ATDs was confirmed and in about 5% of these cases genes were tagged. CONCLUSIONS: The novel strategy of first genotyping and then phenotyping a tagging population as proposed here is, in particular, applicable for long-lived, difficult to transform plant species. We could demonstrate the power of the ATDs transposon approach and the simplicity to induce ATDs transposition in vitro. Since a transposon is able to pass chromosomal boundaries, only very few primary transposon-carrying transgenic lines are required for the establishment of large transposon tagging populations. In contrast to T-DNA-based activation tagging, which is plagued by a lack of transformation efficiency and its time consuming nature, this for the first time, makes it feasible one day to tag (similarly to Arabidopsis) every gene within a perennial plant genome. PMID- 22309469 TI - Acute abdominal compartment syndrome complicating a colonoscopic perforation: a case report. AB - INTRODUCTION: A perforation occurring during colonoscopy is an extremely rare complication that may be difficult to diagnose. It can be responsible for acute abdominal compartment syndrome, a potentially lethal complex pathological state in which an acute increase in intra-abdominal pressure may provoke the failure of several organ systems. CASE PRESENTATION: We report a case of acute abdominal compartment syndrome after perforation of the bowel during a colonoscopy in a 60 year-old North African man with rectal cancer, resulting in respiratory distress, cyanosis and cardiac arrest. Our patient was treated by needle decompression after the failure of cardiopulmonary resuscitation. An emergency laparotomy with anterior resection, including the perforated sigmoid colon, was then performed followed by immediate anastomosis. Our patient remains alive and free of disease three years later. CONCLUSION: Acute abdominal compartment syndrome is a rare disease that may occasionally occur after a colonoscopic perforation. It should be kept in mind during colonoscopy, especially considering its simple salvage treatment. PMID- 22309470 TI - Enhancing the effectiveness of juvenile drug courts by integrating evidence-based practices. AB - OBJECTIVE: The primary purpose of this study was to test a relatively efficient strategy for enhancing the capacity of juvenile drug courts (JDC) to reduce youth substance use and criminal behavior by incorporating components of evidence-based treatments into their existing services. METHOD: Six JDCs were randomized to a condition in which therapists were trained to deliver contingency management in combination with family engagement strategies (CM-FAM) or to continue their usual services (US). Participants included 104 juvenile offenders (average age = 15.4 years; 83% male; 57% White, 40% African American, 3% Biracial). Eighty-six percent of the youths met criteria for at least 1 substance use disorder, and co occurring psychiatric diagnoses were highly prevalent. Biological and self-report measures of substance use and self-reported delinquency were assessed from baseline through 9 months postrecruitment. RESULTS: CM-FAM was significantly more effective than US at reducing marijuana use, based on urine drug screens, and at reducing both crimes against persons and property offenses. Such favorable outcomes, however, were not observed for the self-report measure of substance use. Although some variation in outcomes was observed between courts, the outcomes were not moderated by demographic characteristics or co-occurring psychiatric disorders. CONCLUSIONS: The findings suggest that JDC practices can be enhanced to improve outcomes for participating juvenile offenders. A vehicle for promoting such enhancements might pertain to the development and implementation of program certification standards that support the use of evidence-based interventions by JDCs. Such standards have been fundamental to the successful transport of evidence-based treatments of juvenile offenders. PMID- 22309471 TI - Family factors predict treatment outcome for pediatric obsessive-compulsive disorder. AB - OBJECTIVE: To examine family conflict, parental blame, and poor family cohesion as predictors of treatment outcome for youths receiving family-focused cognitive behavioral therapy (FCBT) for obsessive-compulsive disorder (OCD). METHOD: We analyzed data from a sample of youths who were randomized to FCBT (n = 49; 59% male; M age = 12.43 years) as part of a larger randomized clinical trial. Youths and their families were assessed by an independent evaluator (IE) pre- and post FCBT using a standardized battery of measures evaluating family functioning and OCD symptom severity. Family conflict and cohesion were measured via parent self report on the Family Environment Scale (Moos & Moos, 1994), and parental blame was measured using parent self-report on the Parental Attitudes and Behaviors Scale (Peris, Benazon, et al., 2008b). Symptom severity was rated by IEs using the Children's Yale-Brown Obsessive Compulsive Scale (Scahill et al., 1997). RESULTS: Families with lower levels of parental blame and family conflict and higher levels of family cohesion at baseline were more likely to have a child who responded to FCBT treatment even after adjusting for baseline symptom severity compared with families who endorsed higher levels of dysfunction prior to treatment. In analyses using both categorical and continuous outcome measures, higher levels of family dysfunction and difficulty in more domains of family functioning were associated with lower rates of treatment response. In addition, changes in family cohesion predicted response to FCBT, controlling for baseline symptom severity. CONCLUSION: Findings speak to the role of the family in treatment for childhood OCD and highlight potential targets for future family interventions. PMID- 22309472 TI - Gender differences in the maintenance of response to cognitive behavior therapy for posttraumatic stress disorder. AB - OBJECTIVE: To examine potential differential responses in men and women to cognitive behavior therapy for posttraumatic stress disorder (PTSD). METHOD: Fifty-two men and 56 women diagnosed with PTSD participated in randomized controlled trials of cognitive behavior therapy for PTSD. Participants were randomly allocated to either (a) exposure-only therapy (Ex) or (b) exposure-based treatment combined with cognitive restructuring (ExCR). RESULTS: There were no significant differences between men and women in treatment response immediately after treatment in either Ex or ExCR. At 6-month follow-up, men displayed significantly more severe PTSD symptoms in the Ex group compared with women in the Ex group, and compared with men and women in the ExCR conditions. CONCLUSIONS: These findings suggest that men with PTSD have a reduced maintenance of treatment gains following exposure therapy compared with women, but display less relapse if exposure therapy is combined with cognitive therapy. These findings are consistent with evidence that women recall emotional memories and retain extinction memories more strongly than men, which may facilitate emotional processing and long-term treatment gains. PMID- 22309473 TI - The effect of perceived child anxiety status on parental latency to intervene with anxious and nonanxious youth. AB - OBJECTIVE: We examined the effect of perceived child anxiety status on parental latency to intervene with anxious and nonanxious youth. METHOD: Parents (68) of anxiety-disordered (PAD) and nonanxiety-disordered (PNAD; 56) children participated. Participants listened and responded to an audio vignette of a parent-child interaction: Half were told the child was anxious, and half were given a neutral description. Participants completed measures of anxiety and emotional responding before and after the audio vignette and signaled when the mother on the vignette should accommodate the child. RESULTS: Whereas PNAD responded significantly faster when provided with neutral information about the child than when told the child was anxious, PAD did not differ in response latency. However, PAD exhibited a significant increase in state anxiety and negative affect and a decrease in positive affect after the vignette, whereas PNAD did not. CONCLUSIONS: Results suggest that PNAD are more flexible and adaptable in their parenting behavior than PAD and that the greater anxiety and emotional lability of PAD may influence their parenting. Suggestions for research are discussed. PMID- 22309474 TI - Treatment of comorbid attention-deficit/hyperactivity disorder and anxiety in children: a multiple baseline design analysis. AB - OBJECTIVE: The present study evaluated a 10-week psychosocial treatment designed specifically for children with attention-deficit/hyperactivity disorder (ADHD) and a comorbid anxiety disorder. METHOD: Using a nonconcurrent multiple baseline design, the authors treated 8 children ages 8-12 with ADHD, combined type, and at least 1 of 3 major anxiety disorders (separation anxiety disorder, generalized anxiety disorder, social phobia). The integrated treatment protocol involved parent management training for ADHD and family-based cognitive-behavioral therapy for anxiety. Pretreatment assessments included semistructured diagnostic interviews and other standardized measures to determine study eligibility. Children were randomized to 1 of 3 baseline control conditions (i.e., 2, 3, or 4 weeks) and subsequently treated in a university-based psychosocial treatment clinic. Weekly assessments of ADHD and anxiety disorder symptoms occurred throughout treatment and comprehensive assessments were obtained at pretreatment, 1-week posttreatment, and 6-months posttreatment. RESULTS: Single-case results supported greater success in the treatment phase relative to the baseline phase for both ADHD and anxiety symptoms, and ADHD and anxiety symptoms appeared to change concurrently. Pre-post group analyses revealed significant and clinically meaningful improvements in ADHD and anxiety symptoms at 1-week posttreatment, but only anxiety symptoms moved into the subclinical range. At 6-months follow-up, treatment effects were maintained with new movement into the subclinical range for ADHD. CONCLUSIONS: The present study provides initial data on an integrated treatment protocol for ADHD and anxiety. Further replication and evaluation are needed. Implications of the findings are discussed. PMID- 22309475 TI - Nutritional behavior of cyclists during a 24-hour team relay race: a field study report. AB - BACKGROUND: Information about behavior of energy intake in ultra-endurance cyclists during a 24-hour team relay race is scarce. The nutritional strategy during such an event is an important factor which athletes should plan carefully before the race. The purpose of this study was to examine and compare the nutritional intake of ultra-endurance cyclists during a 24-hour team relay race with the current nutritional guidelines for endurance events. Additionally, we analyzed the relationship among the nutritional and performance variables. METHODS: Using a observational design, nutritional intake of eight males (mean +/ SD: 36.7 +/- 4.7 years; 71.6 +/- 4.9 kg; 174.6 +/- 7.3 cm; BMI 23.5 +/- 0.5 kg/m2) participating in a 24-hour team relay cycling race was assessed. All food and fluid intake by athletes were weighed and recorded. Additionally, distance and speed performed by each rider were also recorded. Furthermore, before to the race, all subjects carried out an incremental exercise test to determine two heart rate-VO2 regression equations which were used to estimate the energy expenditure. RESULTS: The mean ingestion of macronutrients during the event was 943 +/- 245 g (13.1 +/- 4.0 g/kg) of carbohydrates, 174 +/- 146 g (2.4 +/- 1.9 g/kg) of proteins and 107 +/- 56 g (1.5 +/- 0.7 g/kg) of lipids, respectively. This amount of nutrients reported an average nutrient intake of 22.8 +/- 8.9 MJ which were significantly lower compared with energy expenditure 42.9 +/- 6.8 MJ (P = 0.012). Average fluid consumption corresponded to 10497 +/- 2654 mL. Mean caffeine ingestion was 142 +/- 76 mg. Additionally, there was no relationship between the main nutritional variables (i.e. energy intake, carbohydrates, proteins, fluids and caffeine ingestion) and the main performance variables (i.e. distance and speed). CONCLUSIONS: A 24-hour hours cycling competition in a team relay format elicited high energy demands which were not compensated by energy intake of the athletes despite that dietary consumption of macronutrients did not differ to the nutritional guidelines for longer events. PMID- 22309476 TI - Postural strategies in diabetes patients with peripheral neuropathy determined using cross-correlation functions. AB - BACKGROUND: Although postural control strategies have been largely explored in diabetes patients with peripheral neuropathy, the literature on their postural control strategies related to peripheral neuropathy level and task complexity is still limited. The aim of this study is then to investigate how balance task difficulty influences postural strategies in diabetes patients with peripheral neuropathy. SUBJECTS AND METHODS: Postural strategies and instability were evaluated in 25 diabetes patients during four standing tasks. The root mean square value of the anterior-posterior angular velocity, measured at the trunk and the ankle, was investigated and analyzed using cross-correlation functions (CCFs). Correlations between balance and clinical variables were analyzed. RESULTS: A significant decrease in CCFs between trunk and ankles was observed under dynamic balance conditions. Correlations were observed between postural strategies and balance instability with the level of peripheral neuropathy and with hip and ankle strength. CONCLUSION: Postural strategies are influenced by more demanding standing tasks and correlated with the level of peripheral neuropathy and strength of muscles in diabetes patients. PMID- 22309477 TI - Discrepancies between reported self-monitored blood glucose results and point-of care hemoglobin A1c in children with diabetes: lessons to be learned. AB - BACKGROUND: The hemoglobin A1c (HbA1c) assay is considered the gold standard for assessing glycemic control in children and adolescents with type 1 diabetes mellitus (T1DM). In recent years, point-of-care (POC) testing has been more commonly used in the outpatient clinic. However, despite its popularity, little is known about the accuracy of the POC methods in children. PATIENTS AND METHODS: In this case series, we describe seven children-six with T1DM and one with type 2 diabetes mellitus-who had major discrepancies between measured POC HbA1c via A1cNow+((r)) (Bayer Healthcare Metrika, Sunnyvale, CA) and self-monitored blood glucose records. RESULTS: In six subjects, the discrepancy was explained by the presence of the hemoglobin S trait, and an additional subject had the hemoglobin C trait. CONCLUSIONS: This report demonstrates that as with all laboratory tests, the HbA1c test is subject to limitations, particularly in children with hemoglobin variants. Increased awareness regarding these limitations among healthcare professionals is paramount, especially with the increased use of the HbA1c POC method in the medical community. Failure to recognize these limitations can lead to unnecessary medical, financial, and social interventions that could have profound impact on the patient-doctor relationship. PMID- 22309478 TI - Catabolism and biotechnological applications of cholesterol degrading bacteria. AB - Cholesterol is a steroid commonly found in nature with a great relevance in biology, medicine and chemistry, playing an essential role as a structural component of animal cell membranes. The ubiquity of cholesterol in the environment has made it a reference biomarker for environmental pollution analysis and a common carbon source for different microorganisms, some of them being important pathogens such as Mycobacterium tuberculosis. This work revises the accumulated biochemical and genetic knowledge on the bacterial pathways that degrade or transform this molecule, given that the characterization of cholesterol metabolism would contribute not only to understand its role in tuberculosis but also to develop new biotechnological processes that use this and other related molecules as starting or target materials. PMID- 22309479 TI - Preparation, characterisation and viability of encapsulated Trichoderma harzianum UPM40 in alginate-montmorillonite clay. AB - Microencapsulation is a process by which tiny parcels of an active ingredient are packaged within a second material for the purpose of shielding the active ingredient from the surrounding environment. This study aims to determine the ability of the microencapsulation technique to improve the viability of Trichoderma harzianum UPM40 originally isolated from healthy groundnut roots as effective biological control agents (BCAs). Alginate was used as the carrier for controlled release, and montmorillonite clay (MMT) served as the filler. The encapsulated Ca-alginate-MMT beads were characterised using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The FTIR results showed the interaction between the functional groups of alginate and MMT in the Ca-alginate-MMT beads. Peaks at 1595, 1420 and 1020 cm(-1) characterised alginate, and peaks at 1028 and 453 cm( 1) characterised MMT; both sets of peaks appeared in the Ca-alginate-MMT FTIR spectrum. The TGA analysis showed an improvement in the thermal stability of the Ca-alginate-MMT beads compared with the alginate beads alone. SEM analysis revealed a homogeneous distribution of the MMT particles throughout the alginate matrix. T. harzianum UPM40 was successfully encapsulated in the Ca-alginate-MMT beads. Storage analysis of the encapsulated T. harzianum UPM40 showed that the low storage temperature of 5 degrees C resulted in significantly (p < 0.05) better storage compared with room temperature (30 degrees C). PMID- 22309480 TI - Swelling behaviour and controlled drug release from cross-linked kappa carrageenan/NaCMC hydrogel by diffusion mechanism. AB - We studied a model system of controlled drug release using beta-carotene and kappa-carrageenan/NaCMC hydrogel as a drug and a device, respectively. Different concentrations of genipin were added to crosslink the beta-carotene loaded beads by using the dripping method. Results have shown that the cross-linked beads possess lower swelling ability in all pH conditions (pH 1.2 and 7.4), and swelling ratio decreases with increasing genipin concentration. Microstructure study shows that cross-linking has enhanced the stability and structure of the beads network. Determination of diffusion coefficient for the release of encapsulated beta-carotene indicates less diffusivity when beads are cross linked. Swelling models using adaptive neuro fuzzy show that using genipin as a cross-linker in the kC/NaCMC hydrogels affects the transport mechanism. The model shows very good agreement with the experimental data that indicates that applying ANFIS modelling is an accurate, rapid and simple way to model in such a case for controlled release applications. PMID- 22309481 TI - Effects of cyclodextrins on the flavor of goat milk and its yogurt. AB - Goat milk fat includes several branched chain fatty acids (BCFAs), like 4 methyloctanoic acid, which when free, are responsible for goaty flavor. This flavor limits the market opportunities for goat milk. Prior research showed that cyclodextrins (CDs) can reduce goaty flavor, presumably by binding free fatty acids. This research extends that observation. In odor ranking trials in citrate buffer at pH 4.8, beta-CD concentrations between 0% and 0.35% were increasingly effective in reducing odor intensity due to 4-methyloctanoic acid, but only when present in high molar excess. alpha-CD was also effective, but gamma-CD was not. In lipase-treated goat milk only beta-CD was effective but at much lower molar excess, a difference potentially explained by several factors. One was that BCFAs bind to CDs in marked preference to their straight chain isomers. Displacement experiments with phenolphthalein disproved that hypothesis. The ability of beta CD to reduce goaty flavor intensity extended to yogurt. An analytical panel showed that flavor of goat yogurt was reduced by addition of beta-CD, but only if added before heating and fermentation. A hedonic trial showed that consumers preferred unsweetened and sweet/vanilla-flavored goat yogurt more when beta-CD was included, P = 0.004 and 0.016, respectively. Males liked all yogurts more than females (P < 0.01), but there was a treatment * gender interaction (P = 0.016) for sweet/vanilla yogurt: sweet/vanilla masked the goaty flavor for males but not females. This results parallels previously demonstrated gender effects for sheepmeat flavor caused by BCFAs. PRACTICAL APPLICATION: beta-Cyclodextrin masks goaty flavor in yogurt, and with its GRAS status means it could be used in commercial goat yogurts and similar products so the real or perceived nutritional advantages of goat milk are not lost to goaty flavor. PMID- 22309482 TI - Diphenylamine residues in apples caused by contamination in fruit storage facilities. AB - The potential of fruit storage facilities that are contaminated with the widely used chemical antioxidant diphenylamine to cross-contaminate untreated apples (Malus * domestica Borkh.) was studied. A new sample preparation method identified the storage room paint, contaminated from past treatments, as the major source of cross-contamination in the analyzed facilities. Diphenylamine amounts of up to 917 g were found in a single storage room and were shown to correlate with the extent of cross-contamination on stored apples. Our data support a diffusion-based mechanism where the wall paint releases the antioxidant to the storage room atmosphere even years after the last treatment. Given the extent of cross-contamination found in our model experiments and under commercial storage conditions, we deduce a significant risk of exceeding the potentially upcoming maximum residue level of 0.01 mg kg(-1) on stored fruit in contaminated rooms even years after the last diphenylamine treatment. PMID- 22309483 TI - Cynandione A mitigates ischemic injuries in rats with cerebral ischemia. AB - Cynandione A, an acetophenone from the roots of Cynanchum auriculatum and other species in the genus attenuates neurotoxicity of a variety of neurotoxic agents such as l-glutamate in vitro. In this study, we sought to further characterize the neuroprotective effects of cynandione A and other acetophenones from the roots of C. auriculatum in pheochromocytoma tumor cell line PC12 and investigate whether cynandione A protected against ischemic injuries in rats with experimentally induced cerebral ischemia. Viability assays using the 2-(2-methoxy 4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophen-yl)-2H-tetrazolium monosodium salt method and lactate dehydrogenase (LDH) release assays showed that cynandione A dose-dependently attenuated glutamate-induced cytotoxicity. Comparative proteomic analysis by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight MS/MS of PC12 cells treated with cynandione A showed 10 MUM cynandione A caused broad changes in protein expression in PC12 cells including down-regulation of high mobility group box 1 (HMGB1) and dihydropyrimidinase-like 2 (DPYSL2). Immunoblotting studies showed that 10 MUM cynandione A aborted glutamate-induced increase in DPYSL2 and HMGB1 levels in PC12 cells and 30 mg/kg cynandione A also attenuated the rise in HMGB1 levels and mitigated DPYSL2 cleavage in brain tissues of rats with cerebral ischemia. Furthermore, rats with cerebral ischemia treated with 30 mg/kg cynandione A exhibited markedly improved neurological deficit scores at 24 and 72 h compared with control and a 7.2% reduction in cerebral infarction size at 72 h (p < 0.05 vs. control). Our findings demonstrated that cynandione A mitigated ischemic injuries and should be further explored as a neuroprotective agent for ischemic stroke. PMID- 22309484 TI - Ichthyophthirius multifiliis as a potential vector of Edwardsiella ictaluri in channel catfish. AB - There is limited information on whether parasites act as vectors to transmit bacteria in fish. In this trial, we used Ichthyophthirius multifiliis and fluorescent Edwardsiella ictaluri as a model to study the interaction between parasite, bacterium, and fish. The percentage (23-39%) of theronts fluorescing after exposure to E. ictaluri was significantly higher than control theronts (~ 6%) using flow cytometry. Theronts exposed to E. ictaluri at 4 * 10(7) CFU mL( 1) showed a higher percentage (~ 60%) of fluorescent theronts compared to those (42%) exposed to 4 * 10(3) CFU mL(-1) at 4 h. All tomonts (100%) carried the bacterium after exposure to E. ictaluri. Edwardsiella ictaluri survived and replicated during tomont division. Confocal microscopy demonstrated that E. ictaluri was associated with the tomont surface. Among theronts released from tomonts exposed to E. ictaluri, 31-66% were observed with attached E. ictaluri. Sixty percent of fish exposed to theronts treated with 5 * 10(7) E. ictaluri mL( 1) were positive for E. ictaluri at 4 h as determined by qPCR or fluorescent microscopy. Fluorescent E. ictaluri were observed on trophonts in skin and gill wet mounts of dead fish. This study demonstrated that Ich could vector E. ictaluri to channel catfish. PMID- 22309485 TI - Sleep problems and heart rate variability over the working day. AB - The purpose of this study was to discover whether greater sleep problems are associated with reduced heart rate variability during working hours and at night, and to determine whether this association is in part mediated by experienced affective states. This study involved 199 working women with a mean age of 33.8years. Sleep problems were assessed with the Jenkins Sleep Problems Scale, and the Day Reconstruction Method was used to measure positive affect and stress on the evening before and during the working day. Heart rate variability was indexed by the mean square root of the successive standard difference in heart period. Disturbed sleep was inversely related to heart rate variability during the working day (P=0.022), independently of demographic and behavioural confounders. Additional adjustment for positive affect and stress did not lead to further reductions in the association between sleep problems and reduced heart rate variability over the work day. Sleep problems were not predictive of reduced night-time heart rate variability. This report extends the findings from experimental studies and clinical samples, and suggests that disturbed sleep might impair heart rate variability in real life settings, in particular during working hours. Reduced heart rate variability might be a potential pathway linking sleep problems with cardiovascular disease. Based on the current data there was little evidence that the inverse associations between sleep problems and heart rate variability were mediated by experienced affective states. PMID- 22309486 TI - High and sustained efficacy after two sessions of topical 5-aminolaevulinic acid photodynamic therapy for basal cell carcinoma: a prospective, clinical and histological 10-year follow-up study. AB - BACKGROUND: Prolonged follow-up data on topical photodynamic therapy (PDT) in basal cell carcinoma (BCC) are necessary for a full evaluation of its effect and for comparison with conventional treatment methods. OBJECTIVES: To assess 10-year long-term PDT efficacy in primary and recurrent BCC and to evaluate clinical and histopathological factors which may be associated with treatment failure. METHODS: We performed a longitudinal study on 60 histologically verified BCCs in 44 patients treated with curettage and one or two sessions of dimethylsulphoxide (DMSO)-supported topical 5-aminolaevulinic acid (ALA)-based PDT. Treated lesions were investigated by clinical and histopathological examination at regular intervals. The main outcomes were 10-year lesion complete response rate using a time-to-event analysis, histological treatment failure and cosmesis. RESULTS: Overall complete response rate for all lesions was 75% (95% confidence interval 64-87%); 60% after one and 87% after two treatment sessions. The response rate was 78% for primary lesions; 63% after one and 90% after two sessions. The cosmetic outcome was rated as good or excellent in 91-100% of evaluated cases. Treatment failure was documented in 15 (25%) of 60 lesions; clinical investigation identified 14 of them. All failures were noted within 3 years of treatment. Male gender, recurrent tumour and one treatment session were factors significantly associated with treatment failure. The only lesion larger than 2.0 cm relapsed. CONCLUSIONS: Two sessions of DMSO-supported topical ALA-PDT and curettage can provide long-term effective treatment results with favourable cosmetic outcome in primary, small BCC. PMID- 22309487 TI - Smartphone applications for pediatric anesthesia. AB - We present a review of smartphone applications (apps) available for pediatric anesthesia. PMID- 22309488 TI - Glycated hemoglobin and associated risk factors in older adults. AB - BACKGROUND: The aim of this study is to investigate the relationships between HbA1c and other risk factors like obesity, functional fitness, lipid profile, and inflammatory status in older adults. Epidemiological evidence suggests that HbA1c is associated with cardiovascular and ischemic heart disease risk. Excess of body weight and obesity are considered to play a central role in the development of these conditions. Age is associated with several risk factors as increased body fat and abdominal fat, deterioration of the lipid profile, diabetes, raising in inflammatory activity, or decreased functional fitness. METHODS: Data were available from 118 participants aged 65-95 years, including 72 women and 46 men. Anthropometric variables were taken, as was functional fitness, blood pressure and heart rate. Blood samples were collected after 12 h fasting, and HbA1c, hs CRP, TG, TC, HDL-C, LDL-C, and glycaemia were calculated. Bivariate and partial correlations were performed to explore associations amongst the variables of interest. Differences between groups were explored by performing factorial analysis of variance. RESULTS: HbA1c levels ranged from 4.6%-9.4% with 93% of the cases below 6.5%. Women had higher HbA1c, glycaemia, TC, BMI, and lower and upper flexibility than men. Men had higher BW, WC, 6-min walking distance, and VO2peak than women. Age, SBP, DBP, HRrest, HRpeak, HDL-C, LDL-C, TG, TG/HDL-C ratio, Log10 hs-CRP, upper and lower strength, and agility and dynamic balance were similar in men and women. HbA1c had positive associations with glycaemia, HDL-C, TG/HDL-C, BW, WC, BMI, but not with functional fitness, TC, LDL-C, Log10 hs-CRP, PAD, or PAS. Obese participants had higher HbA1c than non-obese only when IDF and not USDHHS criteria were applied. CONCLUSIONS: Older women had higher HbA1c than men, even after controlling for BMI. HbA1c associates equally with BW, BMI or WC. Population-based criteria are recommended to classify obesity and to identify higher levels of HbA1c in obese older adults. HbA1c associates with atherogenic dyslipidemia particularly with TG and TG/HDL-C ratio, but not with TC, HDL-C, or LDL-C. HbA1c is not associated with hs-CRP, and with functional fitness and aerobic endurance. PMID- 22309489 TI - PPI therapy is equally effective in well-defined non-erosive reflux disease and in reflux esophagitis: a meta-analysis. AB - BACKGROUND: Symptomatic response to proton pump inhibitor (PPI) therapy in patients with non-erosive reflux disease (NERD) is often reported as lower than in patients with erosive reflux disease (ERD). However, the definition of NERD differs across clinical trials. This meta-analysis aims to estimate the rate of symptom relief in response to PPI in NERD patients. METHODS: MEDLINE (1966-2010), Cochrane Comprehensive Trial Register (1997-2010) and EMBASE (1985-2010) databases were searched and manual searches from studies' references were performed. Randomized clinical trials were selected that included patients with heartburn, and analyzed the effect of short-term PPI treatment. The primary outcome of selected studies was defined as complete or partial heartburn relief. Two reviewers independently extracted data and assessed study quality of selected articles. Random effects models and meta-regression were used to combine and analyze results. KEY RESULTS: The pooled estimate of complete relief of heartburn after 4 weeks of PPI therapy in patients with ERD was 0.72 (95% CI 0.69-0.74) (32 studies), vs 0.50 (0.43-0.57) (eight studies) in empirically treated patients, 0.49 (0.44-0.55) (12 studies) in patients defined as non-erosive by negative endoscopy, and 0.73 (0.69-0.77) (two studies) in patients defined as non-erosive by both negative endoscopy and a positive pH-test. CONCLUSIONS & INFERENCES: In well-defined NERD patients, the estimated complete symptom response rate after PPI therapy is comparable to the response rate in patients with ERD. The previously reported low response rate in studies with patients classified as NERD is likely the result of inclusion of patients with upper gastrointestinal symptoms that do not have reflux disease. PMID- 22309490 TI - Mapping site-specific changes that affect stability of the N-terminal domain of calmodulin. AB - Biophysical tools have been invaluable in formulating therapeutic proteins. These tools characterize protein stability rapidly in a variety of solution conditions, but in general, the techniques lack the ability to discern site-specific information to probe how solution environment acts to stabilize or destabilize the protein. NMR spectroscopy can provide site-specific information about subtle structural changes of a protein under different conditions, enabling one to assess the mechanism of protein stabilization. In this study, NMR was employed to detect structural perturbations at individual residues as a result of altering pH and ionic strength. The N-terminal domain of calmodulin (N-CaM) was used as a model system, and the 1H-15N heteronuclear single quantum coherence (HSQC) experiment was used to investigate effects of pH and ionic strength on individual residues. NMR analysis revealed that different solution conditions affect individual residues differently, even when the amino acid sequence and structure are highly similar. This study shows that addition of NMR to the formulation toolbox has the ability to extend understanding of the relationship between site specific changes and overall protein stability. PMID- 22309492 TI - MicroRNAs: potentially important regulators for schistosome development and therapeutic targets against schistosomiasis. AB - MicroRNAs (miRNAs) are small, endogenous non-coding RNA molecules that regulate gene expression post-transcriptionally by targeting the 3' untranslated region (3' UTR) of messenger RNAs. Since the discovery of the first miRNA in Caenorhabditis elegans, important regulatory roles for miRNAs in many key biological processes including development, cell proliferation, cell differentiation and apoptosis of many organisms have been described. Hundreds of miRNAs have been identified in various multicellular organisms and many are evolutionarily conserved. Schistosomes are multi-cellular eukaryotes with a complex life-cycle that require genes to be expressed and regulated precisely. Recently, miRNAs have been identified in two major schistosome species, Schistosoma japonicum and S. mansoni. These miRNAs are likely to play critical roles in schistosome development and gene regulation. Here, we review recent studies on schistosome miRNAs and discuss the potential roles of miRNAs in schistosome development and gene regulation. We also summarize the current status for targeting miRNAs and the potential of this approach for therapy against schistosomiasis. PMID- 22309491 TI - Transcriptomic and proteomic analyses of the Aspergillus fumigatus hypoxia response using an oxygen-controlled fermenter. AB - BACKGROUND: Aspergillus fumigatus is a mold responsible for the majority of cases of aspergillosis in humans. To survive in the human body, A. fumigatus must adapt to microenvironments that are often characterized by low nutrient and oxygen availability. Recent research suggests that the ability of A. fumigatus and other pathogenic fungi to adapt to hypoxia contributes to their virulence. However, molecular mechanisms of A. fumigatus hypoxia adaptation are poorly understood. Thus, to better understand how A. fumigatus adapts to hypoxic microenvironments found in vivo during human fungal pathogenesis, the dynamic changes of the fungal transcriptome and proteome in hypoxia were investigated over a period of 24 hours utilizing an oxygen-controlled fermenter system. RESULTS: Significant increases in transcripts associated with iron and sterol metabolism, the cell wall, the GABA shunt, and transcriptional regulators were observed in response to hypoxia. A concomitant reduction in transcripts was observed with ribosome and terpenoid backbone biosynthesis, TCA cycle, amino acid metabolism and RNA degradation. Analysis of changes in transcription factor mRNA abundance shows that hypoxia induces significant positive and negative changes that may be important for regulating the hypoxia response in this pathogenic mold. Growth in hypoxia resulted in changes in the protein levels of several glycolytic enzymes, but these changes were not always reflected by the corresponding transcriptional profiling data. However, a good correlation overall (R(2) = 0.2, p < 0.05) existed between the transcriptomic and proteomics datasets for all time points. The lack of correlation between some transcript levels and their subsequent protein levels suggests another regulatory layer of the hypoxia response in A. fumigatus. CONCLUSIONS: Taken together, our data suggest a robust cellular response that is likely regulated both at the transcriptional and post transcriptional level in response to hypoxia by the human pathogenic mold A. fumigatus. As with other pathogenic fungi, the induction of glycolysis and transcriptional down-regulation of the TCA cycle and oxidative phosphorylation appear to major components of the hypoxia response in this pathogenic mold. In addition, a significant induction of the transcripts involved in ergosterol biosynthesis is consistent with previous observations in the pathogenic yeasts Candida albicans and Cryptococcus neoformans indicating conservation of this response to hypoxia in pathogenic fungi. Because ergosterol biosynthesis enzymes also require iron as a co-factor, the increase in iron uptake transcripts is consistent with an increased need for iron under hypoxia. However, unlike C. albicans and C. neoformans, the GABA shunt appears to play an important role in reducing NADH levels in response to hypoxia in A. fumigatus and it will be intriguing to determine whether this is critical for fungal virulence. Overall, regulatory mechanisms of the A. fumigatus hypoxia response appear to involve both transcriptional and post-transcriptional control of transcript and protein levels and thus provide candidate genes for future analysis of their role in hypoxia adaptation and fungal virulence. PMID- 22309493 TI - Blood pressure measurements and left ventricular mass index in hemodialysis patients. AB - Left ventricular hypertrophy (LVH) is the most frequent cardiac abnormality in hemodialysis (HD) patients. It is related to cardiovascular diseases and is an important risk factor for mortality in HD patients. Arterial hypertension is an established risk factor for LVH in HD patients. Inferior vena cava (IVC) diameter is a good indicator of circulating fluid volume; hypervolemia is an important pathogenetic factor of hypertension in HD patients. The purpose of our study was to evaluate possible association between LVH, IVC diameter, and different blood pressure (BP) measurements in HD patients. In the present study, 85 HD patients were included. BP was measured with a standard mercury sphygmomanometer before and after the HD session; the average 1-monthly values of the routine BP measurements were also analyzed. 24- and 48-h ambulatory blood pressure measurements (ABPMs) were performed after the end of HD sessions using a noninvasive ABPM. Average values of systolic and diastolic BP were analyzed separately for the first (HD) and second (interdialytic) day ABPM and for both days together. Using echocardiography, left ventricular mass was measured and left ventricular mass index (LVMI) was calculated. Using ultrasonography, IVC diameter was measured on the interdialytic day. Using multiple regression analysis, we found statistically significant correlations between LVMI and mean monthly postdialysis systolic BP (P < 0.05) and mean 48-h diastolic BP (P < 0.05). Only longer BP measurements (average 1-month post-HD and 48-h ABPM) were associated with LVMI in HD patients. PMID- 22309495 TI - High rates of de novo 15q11q13 inversions in human spermatozoa. AB - Low-Copy Repeats predispose the 15q11-q13 region to non-allelic homologous recombination. We have already demonstrated that a significant percentage of Prader-Willi syndrome (PWS) fathers have an increased susceptibility to generate 15q11q13 deletions in spermatozoa, suggesting the participation of intrachromatid exchanges. This work has been focused on assessing the incidence of de novo 15q11q13 inversions in spermatozoa of control donors and PWS fathers in order to determine the basal rates of inversions and to confirm the intrachromatid mechanism as the main cause of 15q11q13 anomalies.Semen samples from 10 control donors and 16 PWS fathers were processed and analyzed by triple-color FISH. Three differentially labeled BAC-clones were used: one proximal and two distal of the 15q11-q13 region. Signal associations allowed the discrimination between normal and inverted haplotypes, which were confirmed by laser-scanning confocal microscopy.Two types of inversions were detected which correspond to the segments involved in Class I and II PWS deletions. No significant differences were observed in the mean frequencies of inversions between controls and PWS fathers (3.59% +/- 0.46 and 9.51% +/- 0.87 vs 3.06% +/- 0.33 and 10.07% +/- 0.74). Individual comparisons showed significant increases of inversions in four PWS fathers (P < 0.05) previously reported as patients with increases of 15q11q13 deletions.Results suggest that the incidence of heterozygous inversion carriers in the general population could reach significant values. This situation could have important implications, as they have been described as predisposing haplotypes for genomic disorders. As a whole, results confirm the high instability of the 15q11-q13 region, which is prone to different types of de novo reorganizations by intrachromatid NAHR. PMID- 22309496 TI - Theoretical studies on N-O or N-N bond formation from aryl azide catalyzed by iron(II) bromide complex. AB - DFT calculations have been carried out to study the reaction mechanism on N-O or N-N bond formation from aryl azide catalyzed by iron(II) bromide complex. A favorable reaction pathway is proposed to account for the construction of the core structure of 2H-indazoles or 2,1-benzisoxazoles. PMID- 22309497 TI - Editorial: overview of antiangiogenic therapies in hematological malignancies. PMID- 22309498 TI - Histomorphometric analysis of the effects of creatine on rat myometrium. AB - OBJECTIVE: To analyze the myometrial thickness of rats subjected to creatine (Cr) ingestion. STUDY DESIGN: A total of 14 rats was equally divided into the control group (ConGr) receiving 1 ml potable water and the creatine group (CrGr) subjected to the ingestion of 1.6 g/kg Cr diluted in 1 ml potable water. At the end of 8 weeks, the animals were anesthetized (xylazine and ketamine) and sacrificed, the uteri and ovaries stained with hematoxylin and eosin, the thickness of both the myometrium and the epithelium measured and the follicles counted. RESULTS: Analysis revealed a significant increase in thickness of the myometrium in the CrGr (272.26 +/- 66.71MUm) contrasted with that from the ConGr (160.76 +/- 35.65MUm), CrGr > ConGr (p < 0001). CONCLUSION: Our data suggest that Cr changed myometrial morphology in rats by enhancing myometrial thickness, but its action mechanism in the smooth muscle is still unclear. PMID- 22309499 TI - Energy state of InGaAs quantum dots on SiO2-patterned vicinal substrate. AB - The optical properties of In0.8Ga0.2As self-assembled quantum dots (SAQDs) grown on GaAs wire structures formed by utilizing SiO2-patterned exact and 5 degrees off (001) GaAs substrates have been studied with micro-photoluminescence (MU-PL). Single PL peak was occurred for In0.8Ga0.2As SAQDs grown on SiO2-patterned exact (001) GaAs, whereas double PL peaks were showed for SAQDs grown on 5 degrees -off (001) GaAs substrates as the width of the opening windows increased. The power dependent MU-PL spectra show that the first and second peaks of these double peaks were originated from the well-defined ground and excited state, respectively. These results demonstrated that In0.8Ga0.2As SAQDs selectively grown by utilizing SiO2-patterned 5 degrees -off (001) GaAs substrates have well defined zero-dimensional quantum states. PMID- 22309500 TI - The role of accident theory in injury prevention - time for the pendulum to swing back. AB - Injury prevention is a branch of safety sciences. While comprehensive theoretical developments occurred in the wider field in the last decades, little of these developments reached and influenced the injury prevention community. Instead, a clear retro trend 'back to basics' is seen among injury prevention scholars, especially to Dr William Haddon's pioneering work some 50 years ago. This paper intends to draw attention to this polarisation and discuss possible explanations. It is argued that the strong campaign against the accident concept among leading injury prevention groupings became a serious hindrance for theoretical exchange. The underlying process is interpreted in terms of a struggle for ownership over this truly interdisciplinary field of research, unfortunately at the expense of theoretical stagnation in injury prevention circles and lessened interest in collaboration from other scientific areas. This paper is written as a tribute to Professor Leif Svanstrom and his scientific contributions, with special regard to his genuine interest in interdisciplinary research. PMID- 22309501 TI - Protein dynamics in organic media at varying water activity studied by molecular dynamics simulation. AB - In nonaqueous enzymology, control of enzyme hydration is commonly approached by fixing the thermodynamic water activity of the medium. In this work, we present a strategy for evaluating the water activity in molecular dynamics simulations of proteins in water/organic solvent mixtures. The method relies on determining the water content of the bulk phase and uses a combination of Kirkwood-Buff theory and free energy calculations to determine corresponding activity coefficients. We apply the method in a molecular dynamics study of Candida antarctica lipase B in pure water and the organic solvents methanol, tert-butyl alcohol, methyl tert butyl ether, and hexane, each mixture at five different water activities. It is shown that similar water activity yields similar enzyme hydration in the different solvents. However, both solvent and water activity are shown to have profound effects on enzyme structure and flexibility. PMID- 22309502 TI - Ethnic identity and adjustment: the mediating role of sense of community. AB - This study examines the associations of two facets of ethnic identity (private and public ethnic regard) and adjustment (self-esteem and depressive symptoms) as well as the extent to which these relationships are mediated by sense of community with others. Data were drawn from a sample of Latino students (N = 171, 70% women) attending a highly selective university. Extending previous work, students who reported more positive private and public regard reported a greater sense of community with others on campus, which in turn predicted higher self esteem and less depression. These results suggest that one explanation for the ethnic identity-adjustment relationship concerns individuals' connections to others in important social contexts. PMID- 22309503 TI - Perfectionism in African American students: relationship to racial identity, GPA, self-esteem, and depression. AB - This study examined 219 African American college students at predominantly White universities using the constructs of perfectionism, academic achievement, self esteem, depression, and racial identity. Cluster analysis was performed using the Almost Perfect Scale-Revised (APS-R), which yielded three clusters that represented adaptive perfectionists, maladaptive perfectionists, and nonperfectionists. These three groups were compared on their scores on the Rosenberg Self-Esteem Scale (RSES), the Center for Epidemiological Studies Depression Scale (CES-D), the Cross Racial Identity Scale (CRIS), and Grade Point Average (GPA). Adaptive perfectionists reported higher self-esteem and lower depression scores than both the nonperfectionists and maladaptive perfectionists. Adaptive perfectionists had higher GPAs than nonperfectionists. On the racial identity scales, maladaptive perfectionists had higher scores on Pre-Encounter Self Hatred and Immersion-Emersion Anti-White subscales than adaptive perfectionists. The cultural and counseling implications of this study are discussed and integrated. Finally, recommendations are made for future studies of African American college students and perfectionism. PMID- 22309505 TI - Anticoagulatory and antiinflammatory effects of astaxanthin in diabetic rats. AB - Astaxanthin at 0.01 or 0.05% of the diet was supplied to diabetic rats for 12 wk. Astaxanthin intake significantly increased its deposit in plasma, and retained glutathione content, reduced the production of reactive oxygen species, interleukin-6, tumor necrosis factor-alpha, and monocyte chemoattractant protein 1 in blood and kidney of diabetic rats (P < 0.05). Astaxanthin treatments also significantly decreased plasma levels of C-reactive protein and von Willebrand factor in diabetic rats (P < 0.05). Astaxanthin intake at 0.05% significantly diminished plasminogen activator inhibitor-1 and factor VII activities, enhanced antithrombin-III and protein C activities in circulation (P < 0.05). These results support that astaxanthin could attenuate diabetes associated coagulatory, oxidative, and inflammatory stress. PMID- 22309504 TI - Synaptic vesicles are capable of synthesizing the VGLUT substrate glutamate from alpha-ketoglutarate for vesicular loading. AB - Synaptic vesicle loading of glutamate is a pivotal step in glutamate synaptic transmission. The molecular machinery responsible for this step is comprised of v type proton-pump ATPase and a vesicular glutamate transporter. Recent evidence indicates that synaptic vesicles are endowed with glycolytic ATP-synthesizing enzymes, providing energy for immediate use by vesicle-bound proton-pump ATPase. In this study, we provide evidence that synaptic vesicles are also capable of synthesizing the vesicular glutamate transporter substrate glutamate, from alpha ketoglutarate and l-aspartate (as the amino group donor); glutamate thus produced is taken up into vesicles. We also report a finding that alpha-ketoglutarate derived glutamate uptake into synaptic vesicles and aspartate aminotransferase are inhibited by 2,3-pyrazinedicarboxylate. Evidence is given that this is a selective inhibitor for aspartate aminotransferase. These observations provide insight into understanding the nerve endings' mechanism for high efficiency in glutamate transmission. Finding this inhibitor may have implications for further experimentation on the role of alpha-ketoglutarate-derived glutamate in glutamate transmission. PMID- 22309506 TI - IcsA autotransporter passenger promotes increased fusion protein expression on the cell surface. AB - BACKGROUND: Autotransporters are attractive cell surface display vehicles as they lack complex adaptor proteins necessary for protein export. Recent reports have suggested that the native effector domain (alpha domain) and translocation domain (beta domain) interact with each other to drive translocation of the effector domain to the outer membrane. In this report we compared the expression, surface localisation and folding of TEM-1 beta-lactamase (Bla) and maltose binding protein (MalE or MBP) fused to either full length Shigella flexneri IcsA (IcsA) autotransporter or to the beta domain alone (IcsAbeta) to determine the contribution of the native IcsA alpha domain in presenting the fusion proteins on the surface of E. coli K-12 UT5600 (DeltaompT). RESULTS: Expression of IcsA-Bla was greater than IcsAbeta-Bla. High levels of IcsA-MalE were detected but IcsAbeta-MalE was not expressed. All fusion proteins other than IcsAbeta-MalE were localised to the outer membrane and were detected on the surface of UT5600 via immunofluorescence microscopy. All bacteria expressing IcsA-MalE were labelled with both alpha-IcsA and alpha-MBP. UT5600 expressing IcsAbeta-MalE was not labelled with alpha-MBP. A third of UT5600 expressing IcsA-Bla were detectable with alpha-Bla but only 5% of UT5600 (IcsAbeta-Bla) were labelled with alpha-Bla. The correct folding of the Bla moiety when fused to IcsA and IcsAbeta was also retained as UT5600 expressing either fusion protein exhibited a decreased zone of inhibition in the presence of ampicillin. UT5600 expressing IcsA-Bla was more resistant compared to UT5600 expressing IcsAbeta-Bla. CONCLUSIONS: The export mechanism of autotransporters is not well understood but accumulating evidence suggest a critical role for the native effector or alpha domain in facilitating its own export via interactions with the translocation or beta domain. This is the first report directly comparing expression of heterologous proteins fused to the full length IcsA autotransporter and fusion to the beta domain alone. Protein expression and surface presentation of the fusion proteins were dramatically improved when fused to IcsA rather than IcsAbeta. Future studies involved in designing autotransporters as cell surface display vehicles would benefit from including the native alpha domain. This work also provides further evidence for a key interaction between the autotransporter alpha and beta domains. PMID- 22309507 TI - Clonidine does not improve quality of ropivacaine axillary brachial plexus block in children. AB - BACKGROUND: The addition of clonidine to peripheral nerve blocks is controversial in children. OBJECTIVE: The aim of our study was to evaluate the effect of clonidine added to ropivacaine in pediatric axillary brachial plexus block (ABPB). METHODS: Children aged 1-6 years, scheduled to undergo forearm or hand surgery, were recruited into this prospective, double-blind controlled trial. Patients were randomly allocated to receive an ABPB either with ropivacaine 0.2% 0.4 ml . kg(-1) plus saline in 1 ml (RS) or ropivacaine 0.2% 0.4 ml . kg(-1) plus clonidine 1 MUg . kg(-1) in 1 ml (RC). Primary endpoints were quality of postoperative analgesia as assessed by pain scores and total 24-h postoperative analgesia requirements. Secondary outcomes were time to first analgesia request and duration of motor blockade. RESULTS: Sixty patients were recruited (n = 30 per group) into the study. Pain scores were comparable throughout the first 24 h between the two groups. Ten children in the (RS) and six in (RC) groups required supplementary analgesia during the first 24 h (P = 0.24). Children who required further analgesia did so after 288 +/- 94 min in the (RS) and 437 +/- 204 min in the (RC) group (P = 0.06). There was no difference in the duration of motor block [186 +/- 71 and 154 +/- 56 min, P = 0.12 for (RS) and (RC), respectively]. CONCLUSION: Ropivacaine (0.2% 0.4 ml . kg(-1) ) for ABPB provides sufficient postoperative analgesia in children scheduled for forearm or hand surgery. The addition of clonidine to ABPB does not improve overall postoperative analgesia but may increase the time to first analgesia request. PMID- 22309508 TI - Quality assessment of expert answers to lay questions about cystic fibrosis from various language zones in Europe: the ECORN-CF project. AB - BACKGROUND: The European Centres of Reference Network for Cystic Fibrosis (ECORN CF) established an Internet forum which provides the opportunity for CF patients and other interested people to ask experts questions about CF in their mother language. The objectives of this study were to: 1) develop a detailed quality assessment tool to analyze quality of expert answers, 2) evaluate the intra- and inter-rater agreement of this tool, and 3) explore changes in the quality of expert answers over the time frame of the project. METHODS: The quality assessment tool was developed by an expert panel. Five experts within the ECORN CF project used the quality assessment tool to analyze the quality of 108 expert answers published on ECORN-CF from six language zones. 25 expert answers were scored at two time points, one year apart. Quality of answers was also assessed at an early and later period of the project. Individual rater scores and group mean scores were analyzed for each expert answer. RESULTS: A scoring system and training manual were developed analyzing two quality categories of answers: content and formal quality. For content quality, the grades based on group mean scores for all raters showed substantial agreement between two time points, however this was not the case for the grades based on individual rater scores. For formal quality the grades based on group mean scores showed only slight agreement between two time points and there was also poor agreement between time points for the individual grades. The inter-rater agreement for content quality was fair (mean kappa value 0.232 +/- 0.036, p < 0.001) while only slight agreement was observed for the grades of the formal quality (mean kappa value 0.105 +/- 0.024, p < 0.001). The quality of expert answers was rated high (four language zones) or satisfactory (two language zones) and did not change over time. CONCLUSIONS: The quality assessment tool described in this study was feasible and reliable when content quality was assessed by a group of raters. Within ECORN-CF, the tool will help ensure that CF patients all over Europe have equal possibility of access to high quality expert advice on their illness. PMID- 22309509 TI - The lipoprotein components of the Isd and Hts transport systems are dispensable for acquisition of heme by Staphylococcus aureus. AB - Heme is a key molecule for Staphylococcus aureus and is involved in many aspects of oxidative metabolism. Crucially, heme is required for the activity of cytochromes of the electron transport chain. Staphylococcus aureus is able to obtain heme either through biosynthesis or through acquisition from the host. Clinically persistent 'small colony variant' (SCV) forms of S. aureus are frequently deficient for heme biosynthesis, and disruption of the hemB gene produces stable heme-auxotrophic strains that reproduce many SCV phenotypes. We sought to address the role of heme transport in SCVs by deleting components of the two described heme import systems, the iron-regulated surface determinant (Isd) and heme transport system (Hts) in wild-type S. aureus and hemB mutant backgrounds. Analysis of the growth of S. aureus hemB strains either singly or doubly deficient in isdE and htsA in the presence and absence of heme or hemoglobin revealed that S. aureus is able to obtain exogenous heme in the absence of these transporter components. These data suggest the presence of additional, as yet unidentified transporter components that enable S. aureus to internalize exogenous heme and contradict the proposed model that IsdE can transfer heme to the HtsBC permease. PMID- 22309510 TI - Bartonella species in bat flies (Diptera: Nycteribiidae) from western Africa. AB - Bat flies are obligate ectoparasites of bats and it has been hypothesized that they may be involved in the transmission of Bartonella species between bats. A survey was conducted to identify whether Cyclopodia greefi greefi (Diptera: Nycteribiidae) collected from Ghana and 2 islands in the Gulf of Guinea harbour Bartonella. In total, 137 adult flies removed from Eidolon helvum, the straw coloured fruit bat, were screened for the presence of Bartonella by culture and PCR analysis. Bartonella DNA was detected in 91 (66.4%) of the specimens examined and 1 strain of a Bartonella sp., initially identified in E. helvum blood from Kenya, was obtained from a bat fly collected in Ghana. This is the first study, to our knowledge, to report the identification and isolation of Bartonella in bat flies from western Africa. PMID- 22309511 TI - Optimizing adherence of full-thickness skin grafts to the wound bed of the nasal ala with the 'sandwich suture'. PMID- 22309512 TI - 'Noon walk on the asylum lawn' (psychoanalytic observations during counselling sessions at an AIDS clinic). PMID- 22309513 TI - Fifty years of work on the artificial placenta: milestones in the history of extracorporeal support of the premature newborn. AB - The concept of an artificial placenta has been pursued in experimental research since the early 1960s. The principle has yet to be successfully implemented in neonatal care despite the constant evolution in extracorporeal life support technology and advancements in neonatal intensive care in general. For more than three decades, the physical dimensions of the required equipment necessitated pump-driven circuits; however, recent advances in oxygenator technology have allowed exploration of the simpler and physiologically preferable concept of pumpless arteriovenous oxygenation. We expect that further miniaturization of the extracorporeal circuit will allow the implementation of the concept into clinical application as an assist device. To this end, NeonatOx (Fig. 1), a custom-made miniaturized oxygenator with a filling volume of 20 mL, designed by our own group, has been successfully implemented with a preterm lamb model of less than 2000 g body weight as an assist device. We provide an overview of milestones in the history of extracorporeal membrane oxygenation of the preterm newborn juxtaposed against current and future technological advancements. Key limitations, which need to be addressed in order to make mechanical gas exchange a clinical treatment option of prematurity-related lung failure, are also identified. PMID- 22309514 TI - Insulin resistance but not impaired beta-cell function: a key feature in Chinese normal-weight PCOS women with normal glucose regulation. AB - OBJECTIVE: To evaluate insulin sensitivity and beta-cell function in Chinese polycystic ovary syndrome (PCOS) women while taking into account the confounding variables including body mass index (BMI), blood glucose levels, ethnicity, medication history and a family history of type 2 diabetes. STUDY DESIGN: Cross sectional analysis. SETTING: Clinical research center in China. SUBJECTS: 76 PCOS women and 20 age-matched healthy control women. INTERVENTION: No. MAIN OUTCOME MEASURES: All subjects underwent botnia euglycemic-hyperinsulinemic clamp to assess their insulin sensitivity expressed as M value and beta-cell function expressed as deposition index (DI). RESULTS: Compared with age-matched controls, both DI and M (p < 0.05, respectively) value were lower in PCOS group with normal glucose regulation (NGR), and they (p < 0.05, respectively) were the lowest in PCOS group with impaired glucose regulation (IGR). The subgroup analysis showed that compared with normal-weight controls, DI (p = 0.072) was similar but M value (p < 0.05) was lower in normal-weight PCOS group with NGR, and DI (p < 0.05) and M value (p < 0.05) were lower in overweight PCOS group with NGR. DI and M value (p < 0.05, respectively) of overweight PCOS group with IGR were the lowest among all groups. CONCLUSIONS: There was insulin resistance but not impaired beta-cell function in Chinese normal-weight PCOS women with NGR. Insulin resistance may be an intrinsic factor prior to impaired beta-cell function of PCOS. PMID- 22309515 TI - Editorial. Analytical measurement services. PMID- 22309517 TI - Study of electroplated gold by spark source mass spectrometry. PMID- 22309518 TI - Reevaluation of the preparation of organic compounds for the mass spectrometric analysis for oxygen-18. PMID- 22309519 TI - Mass spectrometric isotope ratio measurements and peak area integration using the peak-switching feature of the AEI MS-902. PMID- 22309520 TI - Isotopic analysis of chromium in lunar materials by mass spectrometry of the trifluoroacetylacetonate. PMID- 22309522 TI - Heats of immersion and swelling of cation resins and related model systems in water and nonaqueous solvents. PMID- 22309521 TI - Establishing water contents of hydrogen form resins by heats of immersion. PMID- 22309523 TI - Apparatus for supercritical fluid chromatography with carbon dioxide as the mobile phase. PMID- 22309524 TI - Synergistic effects in ion exchange in mixed solvents-chloride media. PMID- 22309525 TI - Chromatographic separation of molybdenum using an aliphatic .alpha.-hydroxy oxime. PMID- 22309526 TI - Acid interferences in atomic absorption spectrometry. PMID- 22309527 TI - Double modulation-optical scanning and mechanical chopping-in atomic absorption spectrometry using a continuum source. PMID- 22309528 TI - Electrochemistry of phenazine at a platinum electrode in aprotic solvents. PMID- 22309529 TI - Comparative study of a wide variety of polarographic techniques with multifunctional instrumentation. PMID- 22309530 TI - Theoretical and experimental evaluation of multielement analysis by fundamental harmonic alternating current polarography. PMID- 22309531 TI - Electrochemistry of substances solubilized in micelles. Polarography of azobenzene in aqueous surfactant solutions. PMID- 22309532 TI - Titration reactions of alkylaluminum compounds using phenazine indicator. PMID- 22309533 TI - Voltammetric behavior of nitrite ion on platinum in neutral and weakly acidic media. PMID- 22309534 TI - Effects of neutral inorganic salts on potentiometric titration curves of weak bases in nonaqueous solvents. PMID- 22309535 TI - Voltammetric behavior of the carbon dioxide-oxygen-carbonate system in molten alkali nitrates. PMID- 22309536 TI - Simple analog system for simultaneous kinetic analysis. PMID- 22309537 TI - Spectral evaluation of a sealed helium discharge lamp for studies in photoelectron spectroscopy. PMID- 22309538 TI - Pulse overlap effects on linearity and signal-to-noise ratio in photon counting systems. PMID- 22309539 TI - Critical comparison of photon counting and direct current measurement techniques for quantitative spectrometric methods. PMID- 22309540 TI - Automated colorimetric determination of penicillin in fermentation samples using a molybdoarsenic acid-mercuric chloride reagent. PMID- 22309541 TI - Indirect spectrophotometric determination of oxalate using uranium and 4-(2 pyridylazo)resorcinol. PMID- 22309542 TI - Homogeneous liquid-liquid extraction method. Extraction of iron(III) thenoyltrifluoroacetonate by propylene carbonate. PMID- 22309543 TI - Medium effects for single ions in acetonitrile and ethanol-water solvents based on reference-electrolyte assumption. PMID- 22309544 TI - Solubilities and medium effects of tetraphenylgermane, tetraphenylmethane, and tetraphenylsilane in acetonitrile, methanol, and some ethanol-water solvents. PMID- 22309545 TI - Swept electron beam rapid scan spectrophotometer. Qualitative aspects. PMID- 22309546 TI - Analysis of surface oxidized wool fiber by x-ray electron spectrometry. PMID- 22309547 TI - X-ray photoelectron spectrometry of platinum compounds. PMID- 22309549 TI - Indirect spectrophotometric determination of nanomole quantities of oxiranes. PMID- 22309548 TI - Examination of the exchange of deuterium from deuterium oxide in carbon tetrachloride solution with hydrogen in glass using infrared spectrometry. PMID- 22309550 TI - Sodium analysis with a tunable dye laser. PMID- 22309551 TI - Determination of chain branching in epoxy resins by nuclear magnetic resonance spectrometry. PMID- 22309553 TI - Nonaqueous acid-base properties of sodium tetraphenylboron. PMID- 22309552 TI - Utility of the separated air/acetylene flame in atomic fluorescence spectrometry. PMID- 22309554 TI - Determination of sodium dodecyl sulfate in the presence of lauryl alcohol. PMID- 22309555 TI - Use of metal tungsten bronze electrodes in chemical analysis. PMID- 22309556 TI - Role of solvent extraction parameters in liquid membrane ion-selective electrodes. PMID- 22309557 TI - Coated wire ion-selective electrodes. PMID- 22309558 TI - Separation of fluoride and chloride by solvent extraction using triphenylantimony(V) derivatives. PMID- 22309559 TI - Improvements in the determination of sulfur hexafluoride for use as a meterological tracer. PMID- 22309560 TI - Estimation of the equivalent weights of celluloses. PMID- 22309561 TI - Determination of submicrogram quantities of mercury by the coulometric-iodimetric titration of cyanide produced in a ligand-exchange reaction. PMID- 22309562 TI - Determination of absorptivities and ligand association numbers of carbanion salts. PMID- 22309563 TI - Diffusion barrier model for the cyanide ion-selective electrode. PMID- 22309564 TI - Separation of tellurium from selenium and other fission products by precipitation with 1,10-phenanthroline. PMID- 22309565 TI - Criterion for judging the acceptability of analytical methods. PMID- 22309566 TI - Aromatic hydroxylation as an analytical reaction. PMID- 22309567 TI - Nuclear magnetic resonance determination of tert-butyl hydroperoxide. PMID- 22309568 TI - Simple apparatus for performing reactions and filtration operations in the absence of air. PMID- 22309570 TI - Electrolytic calibration technique for dissolved nitrogen determination in seawater by on-stream stripping gas chromatography. PMID- 22309569 TI - Simple device for introduction of mass calibrant into a gas chromatograph-mass spectrometer system. PMID- 22309571 TI - Rapid technique for dissolution of nitrides. PMID- 22309572 TI - Simple equation for linearization of data in differential scanning calorimetric purity determinations. PMID- 22309573 TI - Cucurbit[8]uril mediated donor-acceptor ternary complexes: a model system for studying charge-transfer interactions. AB - A supramolecular self-assembly approach is described which allows for the convenient preparation of a wide range of charge-transfer (CT) donor-acceptor complexes in aqueous solutions. When one equiv of the macrocyclic host cucurbit[8]uril (CB[8]) is added to an aqueous donor and acceptor solution, a heteroternary complex forms inside the host's cavity with a well-defined face-to face pi-pi-stacking geometry of the donor and acceptor. This heteroternary, CB[8] mediated complex offers the opportunity to study the CT phenomena at low concentrations and free from complications arising from any donor-donor and acceptor-acceptor interactions as a result of the large binding affinities and the very high selectivity over the formation of these homoternary complexes. Thus, this supramolocular self-assembly strategy is a practical donor-acceptor mix-and-match approach with synthetic advantages over much more cumbersome tethering schemes. While the characteristic UV/vis features of a few CB[8] ternary systems had been described as a CT band, we present for the first time systematic evidence for the existence of CT interactions between several donor acceptor pairs that are mediated by the host CB[8]. Correlation of the experimentally obtained CT lambda(max) to computed HOMO-LUMO energies demonstrated that the CT process in the host's cavity can be described by the Mulliken model. Furthermore, the literature claim of a "CT driving force" for the formation of CB[8] ternary complexes was scrutinized and evaluated by calorimetric (ITC) and ESI-MS measurements. The findings indicated that neither in the aqueous medium nor in the "gas-phase" is CT of energetic relevance to the Gibbs free binding energy. In contrast, electrostatic considerations combined with solvation effects are much better suited to rationalize the observed trends in binding affinities. Additionally, the CT lambda(max) was found to be much more red-shifted (>=75 nm) inside the CB[8] cavity than in any polar organic solvents or water, indicating a significant stabilization of the CT excited state within the host cavity, further demonstrating the unique electrostatic, polar properties of the host cavity. PMID- 22309574 TI - Contribution of high-b-value diffusion-weighted imaging in determination of brain ischemia in transient ischemic attack patients. AB - BACKGROUND AND PURPOSE: High-b-value diffusion-weighted imaging (DWI) (b = 2,000 and b = 3,000 second/mm(2)) offers theoretical advantages over DWI examinations at b = 1,000 second/mm(2) for detection of acute ischemic stroke. The purpose of this study was to determine whether high-b-value DWI are better than b = 1,000 images in TIA patients. METHODS: We compared DWI obtained with 3 different b values (1,000, 2,000, and 3,000 second/mm(2)) and fluid-attenuated inversion recovery (FLAIR) sequences in 75 consecutive TIA patients. DWI examinations were performed within 3.25 +/- 1.5 days after the onset of symptoms. Presence of ischemic lesion, volume, lesion conspicuity, and lesion distinction were determined. RESULTS: A total of 40 (53.3%) patients revealed ischemic acute lesions with b = 1,000 while 34 (45.3%) were positive on FLAIR. High-b-value DWI did not increase the sensitivity for the detection of acute brain ischemia. The median lesion value increased as the b-value did: .17 mL (interquartile range [IQR] .12-.78) at b = 1,000; .19 mL (IQR .13-1.00) at b = 2,000; .29 mL (IQR .14 1.02) at b = 3,000; and .12 mL (IQR .04-.62 mL) on FLAIR (P < .001). As b-value increased, we observed hyperintensities in white matter that could erroneously be considered as acute ischemia. CONCLUSION: High-b-value DWI did not improve the conspicuity and distinction of the ischemic lesions. PMID- 22309575 TI - The PCNA pseudogenes in the human genome. AB - BACKGROUND: The proliferating cell nuclear antigen (PCNA) is a key protein in the eukaryotic DNA replication and cell proliferation. Following the cloning and characterisation of the human PCNA gene, the question of the existence of pseudogenes in the human genome was raised. FINDINGS: In this short communication we summarise the existing information about the PCNA pseudogenes and critically assess their status. CONCLUSIONS: We propose the existence of at least four valid PCNA pseudogenes, PCNAP1, PCNAP2, LOC392454 and LOC390102. We would like to recommend assignment of a name for LOC392454 as "proliferating cell nuclear antigen pseudogene 3" (alias PCNAP3) and a name for LOC390102 as "proliferating cell nuclear antigen pseudogene 4" (alias PCNAP4). We prompt for more critical evaluation of the existence of a PCNA pseudogene, designated as PCNAP. PMID- 22309576 TI - Positive experiences of caregiving in stroke: a systematic review. AB - OBJECTIVE: To identify positive experiences of caregivers, who are unpaid carers not statutory, looking after stroke survivors by systematically reviewing published quantitative and qualitative studies. DATA SOURCES: Databases were searched from 1999 to 2009 through Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), British Nursing Index (BNI), Allied and Complimentary Medicine Database (AHMED), PsychINFO, EMBASE and Social Care Online. Reference tracking of selected papers was carried out and references of recent reviews related to stroke caregiving were also scrutinised. REVIEW METHODS: The relevance of studies was ascertained by the two authors from abstracts and inclusion and exclusion criteria were then applied. Where there were differences of opinion, full copies were read and consensus achieved by discussion. RESULTS: Three hundred and twenty-three studies were found and nine selected. Exploratory and cross-sectional studies prevailed. A range of positive experiences confirmed the findings of previous studies in both stroke and other long-term illness; care recipients progress was the most common source, other aspects included strengthened relationships, feeling appreciated, increased self esteem. Positive experiences were associated with coping strategies. Changes in positive experiences over time were noted and differences too, for example, between new and experienced caregivers. Conceptual and methodological issues remain. CONCLUSIONS: Caregivers were able to identify positive experiences of caregiving providing a more balanced view of their role. Helping caregivers to identify their own positive experiences will encourage them to manage their situation. Longitudinal research is needed to track changes and positive influences on caregiving. [ IMPLICATIONS FOR REHABILITATION: * There is some evidence that caregivers are able to identify what they value providing a more positive and balanced view of caregiving experiences other than just negative aspects.* Positive aspects of coping are associated with positive experiences. Offering training to caregivers of a cognitive and behavioural nature, which includes a focus on positive experiences, may be beneficial and needs further consideration.* The diversity of caregivers' experiences - both positive and negative - should be taken into account by clinicians when supporting them] PMID- 22309577 TI - Modulation of recombinant, alpha2*, alpha3* or alpha4*-nicotinic acetylcholine receptor (nAChR) function by nAChR beta3 subunits. AB - The nicotinic acetylcholine receptor (nAChR) beta3 subunit is thought to serve an accessory role in nAChR subtypes expressed in dopaminergic regions implicated in drug dependence and reward. When beta3 subunits are expressed in excess, they have a dominant-negative effect on function of selected nAChR subtypes. In this study, we show, in Xenopus oocytes expressing alpha2, alpha3 or alpha4 plus either beta2 or beta4 subunits, that in the presumed presence of similar amounts of each nAChR subunit, co-expression with wild-type beta3 subunits generally (except for alpha3*-nAChR) lowers amplitudes of agonist-evoked, inward peak currents by 20-50% without having dramatic effects (<= 2-fold) on agonist potencies. By contrast, co-expression with mutant beta3(V9'S) subunits generally (except for alpha4beta2*-nAChR) increases agonist potencies, consistent with an expected gain-of-function effect. This most dramatically demonstrates formation of complexes containing three kinds of subunit. Moreover, for oocytes expressing nAChR containing any alpha subunit plus beta4 and beta3(V9'S) subunits, there is spontaneous channel opening sensitive to blockade by the open channel blocker, atropine. Collectively, the results indicate that beta3 subunits integrate into all of the studied receptor assemblies and suggest that natural co-expression with beta3 subunits can influence levels of expression and agonist sensitivities of several nAChR subtypes. PMID- 22309578 TI - Preconception counseling. AB - The preconception counseling visit is an ideal time to evaluate the patient and her future expectations regarding pregnancy. In fact at every patient encounter, whether for acute or chronic care, consideration should be given to any woman who, although not pregnant, may become pregnant, and what effect each ordered procedure, laboratory examination, or medication prescription might have on her or her fetus. If the primary reason for the office visit is preconception counseling there are a few specific components that should be discussed besides a complete history and physical examination. PMID- 22309579 TI - Prenatal care: touching the future. AB - The provision of preconception and prenatal care is a critical and time-honored role for family physicians. It could even be termed the first preventive care a human being receives. It has been suggested by some studies that, because of the continuity of care that is considered a cornerstone of family practice, family physicians provide prenatal care that may improve birth outcome. Although prenatal care is acknowledged as important for a healthy pregnancy and delivery, there is debate regarding the true efficacy of prenatal care. PMID- 22309580 TI - Family medicine obstetrics: pregnancy and nutrition. AB - This article discusses pregnancy and nutrition in 3 main timeframes, the prepregnancy nutritional health evaluation, nutrition during pregnancy, and nutrition during the puerperium, and also includes comments on nutrition and lactation. This article begins with a brief review of the risks of obesity (increased body mass index [BMI]) and anorexia (decreased BMI), with special attention to these undesired conditions during pregnancy, followed by a section on nutrients other than calories. Information on body weight, minerals, and vitamins during pregnancy is reviewed. This article ends with information on nutrition in the postpartum period. PMID- 22309581 TI - Genetic screening and counseling: family medicine obstetrics. AB - Genetic screening and counseling have become routinely offered during prenatal care in the United States, involving invasive and noninvasive options for assessing fetal genetics. As DNA testing continues to expand proportionately to the increasing ability to detect genetic variations, ethical and fiscal concerns arise. Societal shifts, such as delayed childbearing and the associated genetic consequences, have made antenatal genetic screening more common. Still, genetic screening may be confounded by inaccurate information, false-positives, socioeconomic barriers to testing, and cultural differences. This article reviews these concerns and provides a framework for training in family medicine obstetrics training. PMID- 22309582 TI - First trimester complications. AB - Vaginal bleeding, abdominopelvic pain, nausea, and vomiting are common presenting symptoms in early pregnancy. All women of reproductive age who present with abdominal or pelvic pain or with vaginal bleeding should be evaluated for possible pregnancy. There should be a high index of suspicion for ectopic pregnancy in women presenting with abdominal pain and bleeding after approximately 7 weeks of amenorrhea. Investigation for the cause of the bleeding should ensue. Gestational trophoblastic disease should be considered as a possible cause. Treatment options for nausea during pregnancy should be discussed with women with this common symptom. PMID- 22309583 TI - Update on gestational diabetes mellitus. AB - The incidence of gestational diabetes mellitus (GDM) is increasing in the United States. Universal GDM screening is recommended, although evidence of benefit is lacking. Treatment of GDM reduces the risk of shoulder dystocia, preeclampsia, and macrosomia. Intensive treatment is more effective than less-intensive treatment. Traditional management includes diet, exercise, and short- and intermediate-acting insulin regimens. Use of metformin and glyburide is controversial, but evidence supporting safety and efficacy is accumulating. Postpartum screening with a glucose tolerance test rather than a fasting blood glucose level should be performed 6 weeks after delivery. PMID- 22309584 TI - Third-trimester pregnancy complications. AB - Complications arising in the third trimester often challenge the clinician to balance the concern for maternal well-being with the consequences of infant prematurity. The most serious and challenging antepartum issues relate to preterm labor and birth, hypertensive disorders, and bleeding events. This article guides the practitioner through decision-making and management of these problems. PMID- 22309585 TI - Electronic fetal monitoring: family medicine obstetrics. AB - Electronic fetal monitoring assesses fetal health during the prenatal and intrapartum process. Intermittent auscultation does not detect key elements of fetal risk, such as beat-to-beat variability. Family medicine obstetric fellowships have contributed new knowledge to this process by articulating a method of analysis that builds on evidence-based recommendations from the American College of Obstetrics and Gynecology as well as the National Institute of Child Health and Development. This article summarizes the development, interpretation, and management of electronic fetal heart rate patterns and tracings. PMID- 22309586 TI - Complications of labor and delivery: shoulder dystocia. AB - This article reviews one of the less common but most dreaded complications of labor and delivery, shoulder dystocia, an infrequent but potentially devastating event that results from impaction of the fetal shoulders in the maternal pelvis. Shoulder dystocia occurs most commonly in patients without identified risk factors, and can result in both maternal and fetal morbidity. Because the vast majority of cases of shoulder dystocia are unpredictable, obstetric care providers must be prepared to recognize dystocia and respond appropriately in every delivery. Detailed documentation is essential after any delivery complicated by shoulder dystocia. PMID- 22309587 TI - Cesarean delivery. AB - Cesarean delivery rates rose from 20 to 33% of births in the United States from 2006-2009 without an accompanying improvement in neonatal outcomes. The cesarean rate may be safely decreased by increasing vaginal birth after cesarean, encouraging external cephalic version for breech presentation, maintaining operative vaginal delivery skills, and applying stricter criteria for operative intervention in labor dystocia. A variety of cesarean operative techniques are supported by randomized controlled trials. Optimal maternity care outcomes depend on sound medical decision-making, appropriate operative technique and skills, and effective communication between maternity care team members. PMID- 22309588 TI - Postpartum hemorrhage. AB - Postpartum hemorrhage (PPH) is a very common obstetric emergency with high morbidity and mortality rates worldwide. Understanding its etiology is fundamental to effectively managing PPH in an acute setting. Active management of the third stage of labor is also a key component in its prevention. Management strategies include conservative measures (medications, uterine tamponade, and arterial embolization) as well as surgical interventions (arterial ligations, compression sutures, and hysterectomy). Creating a standardized PPH protocol and running simulation-based drills with a multidisciplinary team may also help decrease maternal morbidity and improve perinatal outcomes, although further studies are needed. PMID- 22309589 TI - Intrapartum care the midwifery way: a review. AB - Midwifery offers concepts and techniques for intrapartum care that could be integrated into the practice of a family physician. Normal birth has virtually been replaced by a medicalized model of maternity care in the American health care system, despite research indicating that many interventions are not necessary and even harmful. A low-tech, high-touch approach to low-risk women in labor is evidence based and results in improved perinatal outcomes as well as higher patient satisfaction with the birth experience. PMID- 22309590 TI - The art of prenatal care. PMID- 22309591 TI - Prenatal care. Preface. PMID- 22309592 TI - Characterization of the seminal plasma proteome in men with prostatitis by mass spectrometry. AB - BACKGROUND: Prostatitis is an inflammation of the prostate gland which affects approximately 10% of men. Despite its frequency, diagnosing prostatitis and monitoring patient response to treatment remains frustrating. As the prostate contributes a substantial percentage of proteins to seminal plasma, we hypothesized that a protein biomarker of prostatitis might be found by comparing the seminal plasma proteome of patients with and without prostatitis. RESULTS: Using mass spectrometry, we identified 1708 proteins in the pooled seminal plasma of 5 prostatitis patients. Comparing this list to a previously published list of seminal plasma proteins in the pooled seminal plasma of 5 healthy, fertile controls yielded 1464 proteins in common, 413 found only in the control group, and 254 found only in the prostatitis group. Applying a set of criteria to this dataset, we generated a high-confidence list of 59 candidate prostatitis biomarkers, 33 of which were significantly increased in prostatitis as compared to control, and 26 of which were decreased. The candidates were analyzed using Gene Ontology and Ingenuity Pathway analysis to delineate their subcellular localizations and functions. CONCLUSIONS: Thus, in this study, we identified 59 putative biomarkers in seminal plasma that need further validation for diagnosis and monitoring of prostatitis. PMID- 22309593 TI - Genomic screening for Chlamydophila pneumoniae-specific antigens using serum samples from patients with primary infection. AB - Chlamydophila pneumoniae, an obligate intracellular human pathogen, causes respiratory tract infections. The most common techniques used for the serological diagnosis of C. pneumoniae infections are microimmunofluorescence tests and commercial serological ELISA tests; these are based on the detection of antibodies against whole chlamydial elementary bodies and lipopolysaccharide/outer membrane protein, respectively. Identification of more specific and highly immunodominant antigens is essential for the development of new serodiagnostic assays. To identify novel specific antigens from C. pneumoniae, we screened 455 genes with unknown function in the genome of C. pneumoniae J138. Extracts of Saccharomyces cerevisiae cells expressing GFP-tagged C. pneumoniae proteins were subjected to Western blot analysis using serum samples from C. pneumoniae-infected patients as the primary antibodies. From this comprehensive analysis, 58 clones expressing C. pneumoniae open reading frames, including hypothetical proteins, were identified as antigens. These results have provided useful information for the development of new serological tools for the diagnosis for C. pneumoniae infections and for the development of vaccines in future. PMID- 22309594 TI - Neonatal administration with dexmedetomidine does not impair the rat hippocampal synaptic plasticity later in adulthood. AB - BACKGROUND AND OBJECTIVE: The use of dexmedetomidine (DEX), a selective alpha-2 agonist, in pediatric practice is expanding as a result of its desirable properties. To clarify the long-term neurological consequences of neonatal administration of DEX, we investigated the long-term effects of neonatal administration of DEX on hippocampal synaptic activity. METHODS: The rat pups received a bolus intraperitoneal injection of either 5 or 10 MUg.kg(-1) DEX, or an equivalent volume of vehicle on postnatal day 7 (P7). Nine weeks after administration, evoked potentials (population spike, PS) and long-term potentiation (LTP) in the hippocampal CA1 region of rats were studied in vivo. RESULTS: Dexmedetomidine had a considerable sedative effect at these doses with little respiratory depression on P7. Nine weeks after administration of DEX, the amplitude of PS in the two treated groups was similar to that in the control group. DEX-treated rats showed no impairment in the induction of LTP. Furthermore, the response in PS to the paired stimuli was not impaired by neonatal administration of DEX. CONCLUSION: These findings demonstrate that a single administration of DEX to rats on P7 preserves hippocampal synaptic plasticity as well as synaptic transmission later in life. In view of the some evidence that have demonstrated the permanent detrimental impact of commonly used anesthetics on neurological outcomes after neonatal exposure, our findings may suggest the relative safety of DEX administered as a sedative agent to neonatal animals with regard to the development of hippocampal synaptic functions. PMID- 22309595 TI - Fibroblast growth factor 19 expression correlates with tumor progression and poorer prognosis of hepatocellular carcinoma. AB - BACKGROUND: Although fibroblast growth factor 19 (FGF19) can promote liver carcinogenesis in mice, its involvement in human hepatocellular carcinoma (HCC) has not been well investigated. FGF19, a member of the FGF family, has unique specificity for its receptor FGFR4. This study aimed to clarify the involvement of FGF19 in the development of HCC. METHODS: We investigated human FGF19 and FGFR4 expression in 40 hepatocellular carcinoma specimens using quantitative real time reverse transcription polymerase chain reaction (RT-PCR) analysis and immunohistochemistry. Moreover, we examined the expression and the distribution of FGF19 and FGFR4 in 5 hepatocellular carcinoma cell lines (HepG2, HuH7, HLE, HLF, and JHH7) using RT-PCR and immunohistochemistry. To test the role of the FGF19/FGFR4 system in tumor progression, we used recombinant FGF19 protein and small interfering RNA (siRNA) of FGF19 and FGFR4 to regulate their concentrations. RESULTS: We found that FGF19 was significantly overexpressed in HCCs as compared with corresponding noncancerous liver tissue (P < 0.05). Univariate and multivariate analyses revealed that the tumor FGF19 mRNA expression was an independent prognostic factor for overall and disease-free survival. Moreover, we found that the FGF19 recombinant protein could increase the proliferation (P < 0.01, n = 12) and invasion (P < 0.01, n = 6) capabilities of human hepatocellular carcinoma cell lines and inhibited their apoptosis (P < 0.01, n = 12). Inversely, decreasing FGF19 and FGFR4 expression by siRNA significantly inhibited proliferation and increased apoptosis in JHH7 cells (P < 0.01, n = 12). The postoperative serum FGF19 levels in HCC patients was significantly lower than the preoperative levels (P < 0.01, n = 29). CONCLUSIONS: FGF19 is critically involved in the development of HCCs. Targeting FGF19 inhibition is an attractive potential therapeutic strategy for HCC. PMID- 22309596 TI - Clinical importance of assessment of type 2 diabetes mellitus with visceral obesity. A Japanese perspective. AB - Type 2 diabetes mellitus (T2DM) is a complex heterogeneous group of metabolic disorders including hyperglycemia and impaired insulin action and/or insulin secretion. Obesity T2DM has become a serious problem in Japan as in Western countries, with over-eating and physical inactivity. Obese Asians have mild degree of adiposity, compared with Western subjects. Unlike total body fat, body fat distribution, especially excess accumulation of visceral fat, correlates with various diabetogenic, atherogenic, prothrombotic and proinflammatory metabolic abnormalities, which increase the risk of atherosclerotic cardiovascular disease (ACVD). Obese patients with T2DM have poor glycemic control with disordered eating behaviors, and complications of hypertension and dyslipidemia, leading to ACVD. The major therapies in obese T2DM, hyperinsulinemia and low insulin sensitivity, available for weight loss, especially visceral fat reduction, include caloric restriction, physical activity and behavior modification. On the other hand, the major therapies in non-obese T2DM with insufficient insulin secretion, are insulin-secretory agents and injectable insulin. For clinically meaningful prevention/reduction in the rate of future ACVD in T2DM, it may be important to stratify T2DM subjects into those with and without visceral obesity and design specific management protocols for each group. PMID- 22309597 TI - Ethnic differences in reported unmet needs among male inpatients with severe mental illness. AB - Health services are failing to meet the needs of ethnic minority groups with severe mental illness in the UK. Understanding these unmet social and health needs will assist service providers in developing culturally sensitive and responsive care pathways. Using a cross-sectional design, 165 service users were recruited from 10 acute inpatient wards across four South London boroughs. Needs were assessed using the Camberwell Assessment of Need Short Assessment Schedule and substance dependence and antisocial personality disorder were measured using the Alcohol Use Disorders Identification Test, Drug Use Disorders Identification Test and the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders. African, but not African-Caribbean, heritage continued to predict lower rates of reported unmet needs compared to White British (P < 0.001) following multivariate analysis. Different patterns of unmet needs were observed across ethnic heritage groups. Antisocial personality disorder and alcohol dependence were also independently associated with unmet needs. Consideration of a patient's ethnic identity and comorbidities is essential for effective needs assessment within psychiatric and mental health nursing. PMID- 22309598 TI - Why infest the loved ones--inherent human behaviour indicates former mutualism with head lice. AB - Head lice transmit to new hosts when people lean their heads together. Humans frequently touch their heads to express friendship or love, while this behaviour is absent in apes. We hypothesize that this behaviour was adaptive because it enabled people to acquire head lice infestations as early as possible to provoke an immune response effective against both head lice and body lice throughout the subsequent periods of their life. This cross-immunity could provide some defence against the body-louse-borne lethal diseases like epidemic typhus, trench fever, relapsing fever and the classical plague. Thus the human 'touching heads' behaviour probably acts as an inherent and unconscious 'vaccination' against body lice to reduce the threat exposed by the pathogens they may transmit. Recently, the eradication of body-louse-borne diseases rendered the transmission of head lice a maladaptive, though still widespread, behaviour in developed societies. PMID- 22309599 TI - Characterization of edible coatings consisting of pea starch, whey protein isolate, and Carnauba wax and their effects on oil rancidity and sensory properties of walnuts and pine nuts. AB - Edible coatings made of whey protein isolate (WPI), pea starch (PS), and their combinations with carnauba wax (CW) were prepared and characterized. WPI combined with CW formed stable emulsion while PS with CW formed unstable emulsion and both formulations produced non-homogeneous films. Addition of PS to WPI: CW combination at the ratio of 1:1:1, respectively, resulted in stable emulsion and homogenous films. The emulsion PS: WPI: CW (1:1:2) was stable and formed a continuous film but had less homogenous droplets size distribution when compared to 1:1:1 film. Combined films had a reduced tensile strength and elongation compared to single component films. WPI : CW (1:1) films had higher elastic modulus than the WPI films, but the modulus reduced by the addition of PS. All the coating formulations were effective in preventing oxidative and hydrolytic rancidity of walnuts and pine nuts stored at 25 degrees C throughout the storage (12 d) but were less effective at 50 degrees C. Increasing the concentration of CW from 1:1:1 to 1:1:2 in PS: WPI: CW formulation did not contribute in further prevention of oil rancidity at 25 degrees C. Using of PS: WPI: CW (1:1:1) coating on both nuts significantly (P < 0.05) improved their smoothness and taste but the PS: WPI: CW (1:1:2) coatings imparted unacceptable yellowish color on walnuts. PRACTICAL APPLICATION: Edible coating of walnuts and pine nuts by whey protein isolate, pea starch, and carnauba wax reduced the oxidative and hydrolytic rancidity of the nuts and improved sensory characteristics. PMID- 22309600 TI - Proteomics on the rims: insights into the biology of the nuclear envelope and flagellar pocket of trypanosomes. AB - Trypanosomatids represent the causative agents of major diseases in humans, livestock and plants, with inevitable suffering and economic hardship as a result. They are also evolutionarily highly divergent organisms, and the many unique aspects of trypanosome biology provide opportunities in terms of identification of drug targets, the challenge of exploiting these putative targets and, at the same time, significant scope for exploration of novel and divergent cell biology. We can estimate from genome sequences that the degree of divergence of trypanosomes from animals and fungi is extreme, with perhaps one third to one half of predicted trypanosome proteins having no known function based on homology or recognizable protein domains/architecture. Two highly important aspects of trypanosome biology are the flagellar pocket and the nuclear envelope, where in silico analysis clearly suggests great potential divergence in the proteome. The flagellar pocket is the sole site of endo- and exocytosis in trypanosomes and plays important roles in immune evasion via variant surface glycoprotein (VSG) trafficking and providing a location for sequestration of various invariant receptors. The trypanosome nuclear envelope has been largely unexplored but, by analogy with higher eukaryotes, roles in the regulation of chromatin and most significantly, in controlling VSG gene expression are expected. Here we discuss recent successful proteomics-based approaches towards characterization of the nuclear envelope and the endocytic apparatus, the identification of conserved and novel trypanosomatid-specific features, and the implications of these findings. PMID- 22309601 TI - Differing patterns of methotrexate use for psoriatic disease among dermatologists and rheumatologists. PMID- 22309602 TI - Analysis of matched geographical areas to study potential links between environmental exposure to oil refineries and non-Hodgkin lymphoma mortality in Spain. AB - BACKGROUND: Emissions from refineries include a wide range of substances, such as chrome, lead, nickel, zinc, arsenic, cadmium, benzene, dioxins and furans, all of which are recognized by the International Agency for Research on Cancer (IARC) as carcinogens.Various studies have shown an association between non-Hodgkin lymphoma (NHL) and residence in the vicinity of industrial areas; however, evidence of specific association between refineries and residence in the vicinity has been suggested but not yet established.The aim of this study is to investigate potential links between environmental exposure to emissions from refineries and non-Hodgkin lymphoma mortality in Spain.The spatial distribution of NHL in Spain has an unusual pattern with regions some showing higher risk than others. METHODS: We designed an analysis of matched geographical areas to examine non-Hodgkin lymphoma mortality in the vicinity of the 10 refineries sited in Spain over the period 1997-2006. Population exposure to refineries was estimated on the basis of distance from town of residence to the facility in a 10 km buffer.We defined 10 km radius areas to perform the matching, accounting for population density, level of industrialization and socio-demographic factors of the area using principal components analysis.For the matched towns we evaluated the risk of NHL mortality associated with residence in the vicinity of the refineries and with different regions using mixed Poisson models. Then we study the residuals to assess a possible risk trend with distance. RESULTS: Relative risks (RRs) associated with exposure showed similar values for women and for men, 1.09 (0.97-1.24) and 1.12 (0.99-1.27). RRs for two regions were statistically significant: Canary Islands showed an excess of risk of 1.35 (1.05-1.72) for women and 1.50 (1.18-1.92) for men, whilst Galicia showed an excess of risk of 1.35 (1.04-1.75) for men, but not significant excess for women. CONCLUSIONS: The results suggest a possible increased risk of NHL mortality among populations residing in the vicinity of refineries; however, a potential distance trend has not been shown. Regional effects in the Canary Islands and Galicia are significantly greater than the regional average. PMID- 22309603 TI - How to diagnose and manage Cushing's disease during pregnancy, when hypercortisolism is mild? AB - Diagnosis of mild Cushing's disease (CD) can be difficult in pregnant women, because its clinical and biochemical features can be erroneously interpreted as consequence of the gestation. Corticotropin releasing hormone (CRH) and desmopressin (DDAVP) tests are currently used to confirm CD, but data concerning adrenocorticotropic hormone (ACTH) response during pregnancy are lacking. A woman with mild cushingoid features was evaluated during the first trimester of gestation. Serum cortisol was normal at morning, but increased at midnight and incompletely suppressed by 1-mg dexamethasone overnight administration. Also 24-h urinary free cortisol levels were mildly elevated. She delivered vaginally a healthy newborn at the 39th week of an uneventful pregnancy. After delivery, an ACTH-secreting microadenoma was surgically removed. During the first trimester of gestation and after delivery, human CRH (h-CRH) and DDAVP-stimulated ACTH peaks were higher than those measured in 22 healthy premenopausal women. While the ACTH/h-CRH peak was intermediate between those measured in the healthy women and in 9 CD female patients, ACTH/DDAVP peak was in the range of CD patients and dramatically higher than those of healthy women. However, ACTH increase after h CRH was significantly higher after delivery than during gestation (p < 0.003), while ACTH responses to DDAVP were similar. In pregnant women with mild cushingoid features, h-CRH and DDAVP tests are useful to confirm the diagnosis of CD. Mild hypercortisolism can be well tolerated, but cardiovascular and metabolic parameters should be monitored carefully. PMID- 22309604 TI - Robot-assisted resection of multiple schwannomas of the neck and mediastinum through an axillary approach. AB - A 49-year-old woman was referred to our department for increased schwannoma of the right neck and mediastinum. We chose a robot-assisted endoscopic approach to minimize the operative trauma. After exposure of the thyroid through the right axilla, the neck tumor was resected using the da Vinci Surgical System. A mini thoracotomy was then made in the left third intercostal space through the axillary incision, robotic instruments were introduced across the thoracic cavity, and the tumor was excised circumferentially using the robot. Histopathological examination of both specimens revealed schwannomas. This procedure has benefited the patient with good cosmetic results and allowed her to rapidly resume her daily activities. PMID- 22309606 TI - Ranibizumab for age-related macular degeneration. AB - INTRODUCTION: Age-related macular degeneration (AMD) is the leading cause of blindness in patients over 50 years in the developed world. The wet form of AMD is responsible for the majority of severe vision loss. VEGF-A is a key component in the development of wet AMD. Ranibizumab is an anti-VEGF agent that has established itself as the gold standard in the treatment of neovascular AMD. Herein, we review the pharmacology, pharmacokinetics, efficacy and safety of ranibizumab. AREAS COVERED: Since its approval in 2006, ranibizumab has revolutionized the treatment of wet AMD. In two pivotal Phase III trials, MARINA and ANCHOR, ranibizumab (0.5 mg) prevented moderate visual loss in 90 and 96% of patients, respectively, and improved vision by 15 letters or more in 33 and 40% of patients, respectively. Fixed monthly dosing regimens were compared with quarterly dosing regimens in PIER and EXCITE studies and support the superiority of fixed monthly dosing. The CATT trial revealed that bevacizumab was not inferior to ranibizumab when dosed monthly. As-needed treatment regimens of ranibizumab were also found to be non-inferior to monthly ranibizumab after 1 year of follow-up. EXPERT OPINION: Ranibizumab has positively altered the treatment of wet AMD and offers hope for millions of patients. PMID- 22309607 TI - Transcriptional profiling of the murine cutaneous response during initial and subsequent infestations with Ixodes scapularis nymphs. AB - BACKGROUND: Ixodes scapularis ticks are hematophagous arthropods capable of transmitting many infectious agents to humans. The process of blood feeding is an extended and continuous interplay between tick and host responses. While this process has been studied extensively in vitro, no global understanding of the host response to ticks has emerged. METHODS: To address this issue, we used PCR arrays to measure skin-specific expression of 233 discrete genes at 8 time points during primary and secondary infestations of mice with pathogen-free I. scapularis nymphs. Selected results were then validated at the mRNA and protein levels by additional real-time PCR and bioplex assay. RESULTS: Primary infestation was characterized by the late induction of an innate immune response. Lectin pattern recognition receptors, cytokines, and chemokines were upregulated consistent with increased neutrophil and macrophage migration. Gene ontology and pathway analyses of downregulated genes suggested inhibition of gene transcription and Th17 immunity. During the secondary infestation, additional genes were modulated suggesting a broader involvement of immune cells including CD8 and CD4 positive T lymphocytes. The cytokine response showed a mixed Th1/Th2 profile with a potential for T regulatory cell activity. Key gene ontology clusters observed during the secondary infestation were cell migration and activation. Matrix metalloproteinases were upregulated, apoptosis-related genes were differentially modulated, and immunoreceptor signaling molecules were upregulated. In contrast, transcripts related to mitogenic, WNT, Hedgehog, and stress pathways were downregulated. CONCLUSIONS: Our results support a model of tick feeding where lectin pattern recognition receptors orchestrate an innate inflammatory response during primary infestation that primes a mixed Th1/Th2 response upon secondary exposure. Tick feeding inhibits gene transcription and Th17 immunity. Salivary molecules may also inhibit upregulation of mitogenic, WNT, Hedgehog, and stress pathways and enhance the activity of T regulatory cells, production of IL-10, and suppressors of cytokine signaling molecules (SOCS). This study provides the first comprehensive transcriptional analysis of the murine host response at the I. scapularis bite site and suggests both a potential model of the host cutaneous response and candidate genes for further description and investigation. PMID- 22309608 TI - The association between Toll-like receptor 2 single-nucleotide polymorphisms and hepatocellular carcinoma susceptibility. AB - BACKGROUND: Toll-like receptors (TLR) are key innate immunity receptors participating in an immune response. Growing evidence suggests that mutations of TLR2/TLR9 gene are associated with the progress of cancers. The present study aimed to investigate the temporal relationship of single nucleotide polymorphisms (SNP) of TLR2/TLR9 and the risk of hepatocellular carcinoma (HCC). METHODS: In this single center-based case-control study, SNaPshot method was used to genotype sequence variants of TLR2 and TLR9 in 211 patients with HCC and 232 subjects as controls. RESULTS: Two synonymous SNPs in the exon of TLR2 were closely associated with risk of HCC. Compared with those carrying wild-type homozygous genotypes (T/T), risk of HCC decreased significantly in individuals carrying the heterozygous genotypes (C/T) of the rs3804099 (adjusted odds ratio (OR), 0.493, 95% CI 0.331 - 0.736, P < 0.01) and rs3804100 (adjusted OR, 0.509, 95% CI 0.342 - 0.759, P < 0.01). There was no significant association found in two TLR9 SNPs concerning the risk of HCC. The haplotype TT for TLR2 was associated significantly with the decreased risk of HCC (OR 0.524, 95% CI 0.394 - 0.697, P = 0.000). Inversely, the risk of HCC increased significantly in patients with the haplotype CC (OR 2.743, 95% CI 1.915 - 3.930, P = 0.000). CONCLUSIONS: These results suggested that TLR2 rs3804099 C/T and rs3804100 C/T polymorphisms were closely associated with HCC. In addition, the haplotypes composed of these two TLR2 synonymous SNPs have stronger effects on the susceptibility of HCC. PMID- 22309609 TI - Cancer dynamics for identical twin brothers. AB - In this paper, a new mathematical model is developed to represent the interaction between healthy and cancer cells in the human body, focusing on the role of environmental factors and quality of life in the progression of cancer. We have investigated the dynamic effects of inputs on cancer growth, and provide an explanation of how cancer has variable behavior patterns throughout the lives of different patients. The behavior of the system with input and its trajectory patterns are investigated using trajectory patterns and stability analysis. The analysis suggests that a proper treatment method should change the dynamics of the cancer instead of only reducing the population of cancer cells and treatment burden. PMID- 22309610 TI - Seroepidemiology of human bocavirus in Apulia, Italy. AB - A serological survey was performed to determine the prevalence of antibodies against human bocavirus in an Apulian population. Anti-hBoV IgG antibodies were analysed in 1206 inhabitants (age range, 1month-84years) using a standardized ELISA test based on the use of recombinant hBoV VP2 virus-like particles. In total, 1075 (89.1%) of 1206 participants (mean age 32+/-24.8years) displayed anti hBoV-IgG. The seroprevalence increased significantly (p<0.0001) in children from 2-4years (64.2%) to 5-9years (96.4%). A similar trend was observed in both male and female subjects. In conclusion, our results show that hBoV infection is common in this population, especially in children. PMID- 22309611 TI - Neuroimaging of pediatric intracranial infection--part 2: TORCH, viral, fungal, and parasitic infections. AB - In the second half of this 2-part review, the neuroimaging features of the most common viral, fungal, and parasitic infections of the pediatric central nervous system are discussed. Brief discussions of epidemiology and pathophysiology will be followed by a review of the imaging findings and potential differential considerations. PMID- 22309612 TI - Acanthamoeba differentiation: a two-faced drama of Dr Jekyll and Mr Hyde. AB - The ability of cyst-forming protists such as Acanthamoeba to escape death by transforming into a cyst form, that is resistant to harsh physiological, environmental and pharmacological conditions, has continued to pose a serious challenge to human and animal health. A complete understanding of the fundamental principles of genome evolution and biochemical pathways of cellular differentiation offers unprecedented opportunities to counter detrimental outcomes. Acanthamoeba can elude inhospitable conditions by forming cysts. Here we unravel the processes involved in the phenotypic switching of Acanthamoeba, which are critical in our efforts to find potential targets for chemotherapy. PMID- 22309613 TI - Could gastrointestinal disorders differ in two close but divergent social environments? AB - BACKGROUND: Many public health problems in modern society affect the gastrointestinal area. Knowledge of the disease occurrence in populations is better understood if viewed in a psychosocial context including indicators of the social environment where people spend their lives. The general aim of this study was to estimate the occurrence in the population and between sexes of common gastrointestinal conditions in two neighborhood cities representing two different social environments defined as a "white-collar" and a "blue-collar" city. METHODS: We conducted a retrospective register study using data of diagnosed gastrointestinal disorders (cumulative incidence rates) derived from an administrative health care register based on medical records assigned by the physicians at hospitals and primary care. RESULTS: Functional gastrointestinal diseases and peptic ulcers were more frequent in the white-collar city, while diagnoses in the gallbladder area were significantly more frequent in the blue collar city. Functional dyspepsia, irritable bowel syndrome, and unspecified functional bowel diseases, and celiac disease, were more frequent among women while esophageal reflux, peptic ulcers, gastric and rectal cancers were more frequent among men regardless of social environment. CONCLUSIONS: Knowledge of the occurrence of gastrointestinal problems in populations is better understood if viewed in a context were the social environment is included. Indicators of the social environment should therefore also be considered in future studies of the occurrence of gastrointestinal problems. PMID- 22309614 TI - Methotrexate polyglutamates as a marker of patient compliance and clinical response in psoriasis: a single-centre prospective study. AB - BACKGROUND: Methotrexate is activated by the sequential addition of glutamic acid residues to form methotrexate polyglutamates (MTXPG(1-5)). MTXPG(1-5) inhibit enzymes of the folate-purine-pyrimidine pathways, and longer-chain MTXPG(3-5) species are more active. OBJECTIVES: To determine the pattern of erythrocyte MTXPG(1-5) in patients initiated on oral methotrexate for psoriasis, and to investigate the potential utility of MTXPGs as markers of compliance and/or clinical response. METHODS: This was a single-centre, prospective study of 55 adult patients with chronic plaque psoriasis initiated on weekly oral methotrexate. Erythrocyte MTXPG(1-5) concentrations were measured (at weeks 4, 8, 12, 24 and 52) using high-performance liquid chromatography. Methotrexate responders achieved >= 50% improvement in Psoriasis Area and Severity Index or physician's global score of 'clear'/'nearly clear' at 24 weeks. RESULTS: MTXPG levels were measured in 14-33 patients at each time point. All MTXPG(1-5) species were detected at week 4 of therapy. Steady state for long-chain MTXPG(3-5) and total MTXPG(1-5) was achieved by week 24. MTXPG(3) emerged as the predominant MTXPG species (from week 12 onwards) and reflected overall polyglutamate status (correlating strongly with MTXPG(2-5) , MTXPG(3-5) and MTXPG(4-5) ; R = 0.76 0.95, P < 1.55 * 10(-5)). Age, renal function and sex were not significant determinants of MTXPG(3) concentration. No significant association was identified between MTXPG and adverse events or responder status. CONCLUSIONS: This is the first study to demonstrate the prospective accumulation of MTXPG(1-5) in patients with psoriasis. The detection of MTXPGs early in therapy and the establishment of a steady state with continuous treatment may offer measuring of MTXPG as a test to monitor patient compliance with therapy. Larger studies are required to determine the role of MTXPG as a potential biomarker of clinical response. PMID- 22309615 TI - Relationship among plasma adipokines, insulin and androgens level as well as biochemical glycemic and lipidemic markers with incidence of PCOS in women with normal BMI. AB - Polycystic ovary syndrome (PCOS) is an endocrine disorder in women. Omentin-1 and vaspin are secretary adipokines that are produced by the visceral adipose tissue. These levels change in obese women with PCOS. The aim of this study is to investigate whether omentin and vaspin levels change in nonobese PCOS subjects. This study is a cross-sectional case control study in which 39 women with PCOS were picked out for this study. The inclusion criteria were based on the Rotterdam 2003 diagnostic criteria. The control group consisted of 39 women with normal pelvic sonographic reports having regular menstruation and showing no signs of infertility. The fasting plasma glucose (FPG), triglyceride (TG), Chol, and high-density lipoprotein cholesterol (HDL-C), insulin, testosterone, omentin and vaspin were measured by the enzymatic methods. The differences within these groups were calculated by the un-paired t-test and the Mann-Whitney test. The results from this study show a significant increase in the amount of insulin, testosterone, homeostasis model assessments for insulin resistance, TG and lower HDL in the patient group. No significant differences were seen in omentin, vaspin, FPG, Cho, low-density lipoprotein, very low-density lipoprotein cholesterol, blood urea nitrogen, Cr and homeostasis model assessments for B cell function levels between groups. Results show that PCOS is not a determinant of decreased omentin and vaspin plasma levels and those high androgen level and insulin resistances are warning signs of PCOS. PMID- 22309616 TI - Acute respiratory infections due to enterovirus 68 in Yamagata, Japan between 2005 and 2010. AB - To clarify the epidemiology of enterovirus 68 (EV68), which is one of the most rarely identified enteroviruses, virus isolation and molecular screening using RT PCR was performed on 6307 respiratory specimens collected at pediatric clinics in Yamagata, Japan between 2005 and 2010. In the years 2005-2009, 10, 1, 2, 0, and 2 (40) EV68-positive cases, respectively, were identified by RT-PCR. In 2010, 40 cases were identified altogether: 2 by isolation only, 26 by RT-PCR only, and 12 by both isolation and RT-PCR. Phylogenetic analysis indicated that plural genetically distinct clusters co-circulated. These results suggest that that difficulty in EV68 isolation leads to an underestimation of the prevalence of EV68 infections. PMID- 22309617 TI - Baby Business: a randomised controlled trial of a universal parenting program that aims to prevent early infant sleep and cry problems and associated parental depression. AB - BACKGROUND: Infant crying and sleep problems (e.g. frequent night waking, difficulties settling to sleep) each affect up to 30% of infants and often co exist. They are costly to manage and associated with adverse outcomes including postnatal depression symptoms, early weaning from breast milk, and later child behaviour problems. Preventing such problems could improve these adverse outcomes and reduce costs to families and the health care system. Anticipatory guidance i.e. providing parents with information about normal infant sleep and cry patterns, ways to encourage self-settling in infants, and ways to develop feeding and settling routines before the onset of problems-could prevent such problems. This paper outlines the protocol for our study which aims to test an anticipatory guidance approach. METHODS/DESIGN: 750 families from four Local Government Areas in Melbourne, Australia have been randomised to receive the Baby Business program (intervention group) or usual care (control group) offered by health services. The Baby Business program provides parents with information about infant sleep and crying via a DVD and booklet (mailed soon after birth), telephone consultation (at infant age 6-8 weeks) and parent group session (at infant age 12 weeks). All English speaking parents of healthy newborn infants born at > 32 weeks gestation and referred by their maternal and child health nurse at their first post partum home visit (day 7-10 postpartum), are eligible. The primary outcome is parent report of infant night time sleep as a problem at four months of age and secondary outcomes include parent report of infant daytime sleep or crying as a problem, mean duration of infant sleep and crying/24 hours, parental depression symptoms, parent sleep quality and quantity and health service use. Data will be collected at two weeks (baseline), four months and six months of age. An economic evaluation using a cost-consequences approach will, from a societal perspective, compare costs and health outcomes between the intervention and control groups. DISCUSSION: To our knowledge this is the first randomised controlled trial of a program which aims to prevent both infant sleeping and crying problems and associated postnatal depression symptoms. If effective, it could offer an important public health prevention approach to these common, distressing problems. PMID- 22309618 TI - Vaccines for cytomegalovirus. AB - Cytomegalovirus (CMV) is a leading cause of congenital infection worldwide and therefore is recognized as an important target for vaccine development. Data from natural infections and work done with animal models, including models of congenital infection, provide the rationale for their development. CMV vaccine evaluations were begun in the mid-1970's with an attenuated live virus vaccine, Towne, but this vaccine has not consistently provided protection. Most recently, data from a trial with a subunit glycoprotein B (gB) vaccine administered with the adjuvant MF59 became available. This trial, conducted in post-partum women, demonstrated that the vaccine decreased CMV infections, increasing optimism that a protective CMV vaccine could be developed. Other approaches for CMV that have entered clinical trials include replicons, DNA vaccines, prime boost strategies, and chimeric live viruses. The replicon vaccine included gB and the T cell targets phosphoprotein (pp)65 and Immediate Early (IE)1 while the DNA vaccine was given with a new adjuvant and included gB and pp65. The optimal composition for a CMV vaccine remains to be defined but trials continue with the gB vaccine and others. PMID- 22309620 TI - Subjective cognitive complaints: not to be dismissed. PMID- 22309619 TI - [Medical handovers in ICU: a snapshot of practice in the South West of France]. AB - INTRODUCTION: Medical handover is critical for quality of care in ICU. Time assigned to medical handovers can vary across different units, with significant impact on the organization of medical work. We aimed to study the time spent for medical handover in ICU and its variation across academic, general and private hospitals in the area of the South West of France, the Midi-Pyrenees region. METHODS: Between August and October 2010, we questioned by phone, 86 physicians issued from 19 different ICUs. This prospective observational study mainly focused on four items: unit's characteristics, health diaries organization, medical handovers procedures, and self-assessment of satisfaction for medical handover (numeric scale from 0 to 10). RESULTS: Eleven general hospital centers, three private hospitals, five university hospitals were concerned by the survey. The mean time spent for medical handover was 59+/-35 min on monday morning, significantly longer than other days, evening, and to weekend handovers (P<0.001 for all comparisons). When reporting it to the number of ICU bed, the time spent for handover per patient was significantly shorter in private hospital compared to general and academic hospital (P<0.05 for all comparison). CONCLUSION: Time spent for medical handover is important, with an approximate total time of 1h 30 min on monday, and 1h the other days. Physician in private hospitals spend less time for medical handovers. This fact should be considered for medical timework organization, especially in academic hospital and in hospital with large ICU. PMID- 22309622 TI - Risk factors for the prognosis of acute kidney injury under the Acute Kidney Injury Network definition: a retrospective, multicenter study in critically ill patients. AB - AIM: Despite significant advances in medical management and therapeutics, acute kidney injury (AKI) is still a common and serious complication with high morbidity and mortality in hospitalized patients, especially in patients admitted to the intensive care unit (ICU). The primary purpose of this study is to apply the definition proposed by the Acute Kidney Injury Network (AKIN) to investigate the incidence, 28-day mortality and risk factors for the prognosis of AKI in ICU. METHODS: In this retrospective study, data from a cohort of 4642 patients admitted to five ICUs were analyzed. Univariate and multivariate analyses were performed to investigate the risk factors for prognosis of AKI. RESULTS: A total of 1036 patients were enrolled. AKI occurred in 353 of them (34.1%) under the AKIN criteria and the mortality was 54.4%. Multivariable analysis showed that variables related to the prognosis of AKI were: four or more (>=4) organ failed systems (odds ratio (OR) = 25.612), AKI III (OR = 14.441), AKI II (OR = 4.491), mechanical ventilation (OR = 7.201), sepsis (OR = 4.552), severe acute pancreatitis (OR = 3.299), base serum creatinine (OR = 1.004) and the length of stay in ICU (OR = 1.050). CONCLUSIONS: For critically ill patient, the ICU mortality of AKI was correlated with various independent risk factors, especially AKI II, AKI III, severe acute pancreatitis and multiple organ failed systems. PMID- 22309623 TI - Dysmorphometrics: the modelling of morphological abnormalities. AB - BACKGROUND: The study of typical morphological variations using quantitative, morphometric descriptors has always interested biologists in general. However, unusual examples of form, such as abnormalities are often encountered in biomedical sciences. Despite the long history of morphometrics, the means to identify and quantify such unusual form differences remains limited. METHODS: A theoretical concept, called dysmorphometrics, is introduced augmenting current geometric morphometrics with a focus on identifying and modelling form abnormalities. Dysmorphometrics applies the paradigm of detecting form differences as outliers compared to an appropriate norm. To achieve this, the likelihood formulation of landmark superimpositions is extended with outlier processes explicitly introducing a latent variable coding for abnormalities. A tractable solution to this augmented superimposition problem is obtained using Expectation-Maximization. The topography of detected abnormalities is encoded in a dysmorphogram. RESULTS: We demonstrate the use of dysmorphometrics to measure abrupt changes in time, asymmetry and discordancy in a set of human faces presenting with facial abnormalities. CONCLUSION: The results clearly illustrate the unique power to reveal unusual form differences given only normative data with clear applications in both biomedical practice & research. PMID- 22309624 TI - Female Anopheles gambiae antennae: increased transcript accumulation of the mosquito-specific odorant-binding-protein OBP2. AB - BACKGROUND: New interventions are required to optimally and sustainably control the Anopheles sp. mosquitoes that transmit malaria and filariasis. The mosquito olfactory system is important in host seeking (transmission) and mate finding (reproduction). Understanding olfactory function could lead to development of control strategies based on repelling parasite-carrying mosquitoes or attracting them into a fatal trap. FINDINGS: Our initial focus is on odorant binding proteins with differential transcript accumulation between female and male mosquitoes. We report that the odorant binding protein, OBP2 (AGAP003306), had increased expression in the antennae of female vs. male Anopheles gambiae sensu stricto (G3 strain). The increased expression in antennae of females of this gene by quantitative RT-PCR was 4.2 to 32.3 fold in three independent biological replicates and two technical replicate experiments using A. gambiae from two different laboratories. OBP2 is a member of the vast OBP superfamily of insect odorant binding proteins and belongs to the predominantly dipteran clade that includes the Culex oviposition kairomone-binding OBP1. Phylogenetic analysis indicates that its orthologs are present across culicid mosquitoes and are likely to play a conserved role in recognizing a molecule that might be critical for female behavior. CONCLUSIONS: OBP2 has increased mRNA transcript accumulation in the antennae of female as compared to male A. gambiae. This molecule and related molecules may play an important role in female mosquito feeding and breeding behavior. This finding may be a step toward providing a foundation for understanding mosquito olfactory requirements and developing control strategies based on reducing mosquito feeding and breeding success. PMID- 22309625 TI - Use of larval, parasitic female and egg antigens from Strongyloides venezuelensis to detect parasite-specific IgG and immune complexes in immunodiagnosis of human strongyloidiasis. AB - The aim of this study was to use larval, parasitic female and egg antigens from Strongyloides venezuelensis to detect parasite-specific IgG and immune complexes in human serum samples by enzyme-linked immunosorbent assay (ELISA). In total, 95 serum samples were analysed, consisting of 30 patients harbouring S. stercoralis larvae, 30 healthy subjects and 35 patients with other parasites. Sensitivity, specificity and diagnostic efficiency were calculated. A significant statistical difference was found in the detection of immune complexes and antibodies in patients harbouring S. stercoralis larvae from larval and eggs antigens, with higher positivity using larval antigen. The larval antigen showed the highest values for sensitivity, specificity and diagnostic efficiency in ELISA from detection of immune complexes. For the first time we used IgG anti-larvae, IgG anti-parasitic females or IgG anti-eggs for immune complex detection. We concluded that the association of antibody and immune complex detection could be used in the diagnosis of human strongyloidiasis. PMID- 22309629 TI - Effects of sterol regulatory element-binding protein (SREBP) in chickens. AB - Sterol regulatory element binding protein- 1 and -2 (SREBP-1 and -2) are key transcription factors involved in the biosynthesis of cholesterol and fatty acids. The SREBP have mostly been studied in rodents in which lipogenesis is regulated in both liver and adipose tissue. There is, though, a paucity of information on birds, in which lipogenesis occurs essentially in the liver as in humans. Since a prelude to the investigation of the role of SREBP in lipid metabolism regulation in chicken, we review Size and Tissue expression Pattern of SREBP and role of this protein in chickens. PMID- 22309630 TI - Primary amenorrhea in two sisters: description of a Mexican family with 17alpha hydroxylase-17 lyase deficiency caused by arginine - stop mutation. AB - A rare cause of congental adrenal hyperplasia is 17alpha-hydroxylase deficiency. It results in sexual infantilism, primary amenorrhea in females, pseudohermaphroditism in males, hypertension, and hypokalemia. We studied two female siblings from a rural community in Mexico. The cause of consultation was primary amenorrhea. The proband had low levels of estrogen, progesterone and cortisol. Deoxycorticosterone and corticosterone levels were elevated. The proband was homozygous for a transversion of cytosine to thymine at exon 4 (CGA >TGA), causing a premature stop codon at position 239 (R239X). Analysis of family members showed the presence of this heterozygous mutation in the mother, father and one healthy sibling. In summary, we describe a Mexican family with 17alpha hydroxylase deficiency due to R239X mutation. PMID- 22309631 TI - Role of diluent on the separation of 90Y from 90Sr by solvent extraction and supported liquid membrane using T2EHDGA as the extractant. AB - The separation behaviour of (90)Y from (90)Sr was investigated by diluent variation using solvent extraction and supported liquid membrane techniques employing N,N,N',N'-tetra-2-ethylhexyldiglycolamide (T2EHDGA) as the extractant. Both D(Y) (distribution ratio of Y(III)) and S.F. (separation factor) were found to be high in the solvent extraction studies when chloroform was used as the diluent. Subsequent supported liquid membrane (SLM) studies using PTFE flat sheet membranes containing 0.2M T2EHDGA in various diluents indicated the trend of Y transport as xylene>hexone>chloroform>carbon tetrachloride>n-dodecane+30% iso decanol mixture. However, the Sr(II) transport rates were also high with xylene, hexone, and carbon tetrachloride as the diluents which led us to carry out subsequent studies using chloroform and n-dodecane+30% iso-decanol mixture. Acid variation studies in chloroform system indicated an interesting phenomena of increasing Y(III) transport and decreasing Sr(II) transport with increasing acid concentration. Separation of (90)Y from a mixture of (90)Sr and (90)Y was also attempted. PMID- 22309632 TI - Establishment of Ge-doped optical fibres as thermoluminescence dosimeters for brachytherapy. AB - This study aims to establish the sensitive, ~120 MUm high spatial resolution, high dynamic range Ge-doped optical fibres as thermoluminescence (TL) dosimeters for brachytherapy dose distribution. This requires investigation to accommodate sensitivity of detection, both for the possibility of short range dose deposition from beta components as well as gamma/x-mediated dose. In-air measurements are made at distances close to radionuclide sources, evaluating the fall off in dose along the transverse axis of 133Ba and 60Co radioactive sources, at distances from 2 mm up to 20 mm from their midpoints. Measurements have been compared with Monte Carlo code DOSRZnrc simulations for photon-mediated dose only, agreement being obtained to within 3% and 1% for the 133Ba and 60Co sources, respectively. As such, in both cases it is determined that as intended, beta dose has been filtered out by source encapsulation. PMID- 22309633 TI - Decreased NURR1 and PITX3 gene expression in Chinese patients with Parkinson's disease. AB - BACKGROUND AND PURPOSE: The preferential degeneration of midbrain dopaminergic (mDA) neurons in the substantia nigra pars compacta is the pathological hallmark in Parkinson's disease (PD). The transcription factors NURR1 and PITX3 have been shown to play a crucial role in the maturation and survival of mDA neurons, and both of them were potential susceptibility genes for PD. METHODS: To determine whether NURR1 and PITX3 gene expression are altered in Chinese patients with PD, we measured their gene expression in human peripheral blood lymphocytes (PBL) in 255 patients with PD and 211 age- and gender-matched healthy controls by quantitative real-time PCR technique. RESULTS: We found that both NURR1 and PITX3 gene expression in PBL were significantly decreased in patients with PD as compared with controls (P < 0.0001). Lower levels of NURR1 and PITX3 gene expression were significantly associated with the increased risk for PD in male and older subjects, respectively. CONCLUSIONS: Our results provide useful information that the NURR1 and PITX3 gene expression is decreased in the PBL of Chinese patients with PD, indicating their possible systemic involvement in PD. PMID- 22309634 TI - The role of heat in rubbing and massage-related corneal deformation. AB - PURPOSE: To examine the role of elevated corneal temperature in the development of rubbing/massage-related corneal deformation and the possibility that warm compresses in the management of meibomian gland dysfunction or chalazion could contribute to such adverse responses. METHODS: With reference to reports of corneal deformation associated with meibomian gland dysfunction, chalazion, dacryocystoceles and post-trabeculectomy, the mechanisms for increased corneal temperature due to ocular massage, especially when combined with warm compresses are examined. RESULTS: Several mechanisms for rubbing/massage to elevate corneal temperature have been described, apart from the application of warm compresses or other forms of heat. CONCLUSIONS: Raised corneal temperature helps to explain corneal deformation which develops in association with rubbing or massage in conditions such as keratoconus, chalazion, post-trabeculectomy, post-laser assisted in situ keratomileusis, post-graft and dacryocystoceles. When combined with warm compresses or other methods of heat delivery to the eye, the elevation of corneal temperature appears to explain how meibomian gland dysfunction treatment involving warm compresses and massage could induce rubbing-related deformation. Patients whose management involves iatrogenic ocular massage appear to require screening for risk of corneal deformation. Risk may be increased for patients with a concurrent habit of rubbing their eyes abnormally in response to allergic itch for example. It appears to be possible to modify ocular massage techniques to reduce the risk of corneal deformation. Careful tutoring and follow up using corneal topography appears to be required when massage is prescribed, especially when used in conjunction with heat application. PMID- 22309635 TI - Commentary: Lasers for liposuction: no benefit over tumescent liposuction. PMID- 22309636 TI - Commentary: Advocating for mandatory adverse event reporting. PMID- 22309637 TI - Commentary on Inferiorly based crescentic sliding cheek flaps for the reconstruction of paranasal surgical defects. PMID- 22309638 TI - The synthetic ethylene-vinyl acetate bench model. PMID- 22309639 TI - Re: Polidocanol concentration and time affect the properties of foam used for sclerotherapy. PMID- 22309640 TI - Re: Sentinel node biopsy should be offered in thin melanoma with mitotic rate greater than one. PMID- 22309641 TI - The effectiveness of a trauma-focused psycho-educational secondary prevention program for children exposed to interparental violence: study protocol for a randomized controlled trial. AB - BACKGROUND: Children who witness interparental violence are at a heightened risk for developing psychosocial, behavioral and cognitive problems, as well as posttraumatic stress symptoms. For these children the psycho-educational secondary prevention program 'En nu ik...!' ('It's my turn now!') has been developed. This program includes specific therapeutic factors focused on emotion awareness and expression, increasing feelings of emotional security, teaching specific coping strategies, developing a trauma narrative, improving parent-child interaction and psycho-education. The main study aim is to evaluate the effectiveness of the specific therapeutic factors in the program. A secondary objective is to study mediating and moderating factors. METHODS/DESIGN: This study is a prospective multicenter randomized controlled trial across cities in the Netherlands. Participants (N = 140) are referred to the secondary preventive intervention program by police, social work, women shelters and youth (mental health) care. Children, aged 6-12 years, and their parents, who experienced interparental violence are randomly assigned to either the intervention program or the control program. The control program is comparable on nonspecific factors by offering positive attention, positive expectations, recreation, distraction, warmth and empathy of the therapist, and social support among group participants, in ways that are similar to the intervention program. Primary outcome measures are posttraumatic stress symptoms and emotional and behavioral problems of the child. Mediators tested are the ability to differentiate and express emotions, emotional security, coping strategies, feelings of guilt and parent-child interaction. Mental health of the parent, parenting stress, disturbances in parent-child attachment, duration and severity of the domestic violence and demographics are examined for their moderating effect. Data are collected one week before the program starts (T1), and one week (T2) and six months (T3) after finishing the program. Both intention-to-treat and completer analyses will be done. DISCUSSION: Adverse outcomes after witnessing interparental violence are highly diverse and may be explained by multiple risk factors. An important question for prevention programs is therefore to what extent a specific focus on potential psychotrauma is useful. This trial may point to several directions for optimizing public health response to children's exposure to interparental violence. PMID- 22309642 TI - Reactivity of human convalescent sera with influenza virus hemagglutinin protein mutants at antigenic site A. AB - How the antibodies of individual convalescent human sera bind to each amino acid residue at the antigenic sites of hemagglutinin (HA) of influenza viruses, and how the antigenic drift strains of influenza viruses are selected by human sera, is not well understood. In our previous study, it was found by a binding assay with a chimeric HA between A/Kamata/14/91 (Ka/91) and A/Aichi/2/68 that convalescent human sera, following Ka/91 like (H3N2) virus infection, bind to antigenic site A of Ka/91 HA. Here using chimeric HAs possessing single amino acid substitutions at site A, it was determined how those human sera recognize each amino acid residue at antigenic site A. It was found that the capacity of human sera to recognize amino acid substitutions at site A differs from one person to another and that some amino acid substitutions result in all convalescent human sera losing their binding capacity. Among these amino acid substitutions, certain ones might be selected by chance, thus creating successive antigenic drift. Phylogenetic analysis of the drift strains of Ka/91 showed amino acid substitutions at positions 133, 135 and 145 were on the main stream of the phylogenetic tree. Indeed, all of the investigated convalescent sera failed to recognize one of them. PMID- 22309643 TI - Effects of miltefosine treatment in fibroblast cell cultures and in mice experimentally infected with Neospora caninum tachyzoites. AB - Miltefosine was investigated for its activity against Neospora caninum tachyzoites in vitro, and was shown to inhibit the proliferation of N. caninum tachyzoites cultured in human foreskin fibroblasts (HFF) with an IC50 of 5.2 MUM. Treatment of infected cells with 25 MUM miltefosine for a period of 10 h had only a parasitostatic effect, while after 20 h of treatment parasiticidal effects were observed. This was confirmed by transmission electron microscopy of N. caninum infected and miltefosine-treated HFF. Administration of miltefosine to N. caninum infected Balb/c female mice at 40 mg/kg/day for 14 days resulted in 6 out of 10 mice exhibiting weight loss, ruffled coat and apathy between days 7 and 13 post infection. In the group that received placebo, only 2 out of 8 mice succumbed to infection, but the cerebral burden was significantly higher compared to the miltefosine treatment group. In a second experiment, the time-span of treatment was reduced to 5 days, and mice were maintained without further treatment for 4 weeks. Only 2 out of 9 mice in the miltefosine treatment group exhibited signs of disease, while 8 out of 10 mice succumbed to infection in the placebo group. These results showed that miltefosine hampered the dissemination of parasites into the CNS during experimental N. caninum infection in mice. PMID- 22309644 TI - Chitinase expression in parotid glands of non-obese diabetic mice. AB - OBJECTIVE: This investigation was a basal study that used a mouse model of xerostomia to identify protein biomarkers of xerostomia in saliva. We identified genes expressed differently in parotid glands from non-obese diabetic mice with diabetes and those from control mice; subsequently, we investigated expression of the proteins encoded by these genes in parotid glands and saliva. MATERIALS AND METHODS: DNA microarray and real-time PCR analyses were performed to detect differences between NOD/ShiJcl and C57BL/6JJcl (control) female mice in gene expression from parotid glands or parotid acinar cells. Subsequently, protein expression was assessed using immunoblotting and immunohistochemistry. Similarly, enzyme activity in saliva was assessed using zymography. RESULTS: Based on gene expression analyses, Chia expression was higher in diabetic mice than non diabetic mice and control mice; similarly, expression of chitinase, the protein encoded by Chia, was higher in diabetic mice. Saliva from NOD/ShiJcl mice had more chitinase than saliva from control mice. CONCLUSIONS: Chitinase was highly expressed in parotid acinar cells from diabetic mice compared with non-diabetic and control mice. Increased chitinase expression and enzyme activity may characterize the autoimmune diabetes in mice; however, further investigation is required to assess its use as a biomarker of xerostomia in humans. PMID- 22309645 TI - Prenatal negative life events increases cord blood IgE: interactions with dust mite allergen and maternal atopy. AB - BACKGROUND: Prenatal exposure to both stress and aeroallergens (dust mite) may modulate the fetal immune system. These exposures may interact to affect the newborn immune response. We examined associations between prenatal maternal stress and cord blood total IgE in 403 predominately low-income minority infants enrolled in the Asthma Coalition on Community, Environment, and Social Stress (ACCESS) project. We also examined potential modifying effects of maternal atopy and maternal dust mite exposure. METHODS: The Crisis in Family Systems survey was administered to mothers prenatally, and a negative life event domain score was derived to characterize stress. Dust mite allergen was quantified in dust from pregnant mothers' bedrooms. Cord blood was analyzed for total IgE. Using linear regression, we modeled the relationship of stress with cord blood IgE and interactions of stress with dust mite and/or maternal atopy, adjusting for potential confounders. RESULTS: Higher prenatal maternal stress (beta = 0.09; P = 0.01) was associated with increased cord blood IgE. The interactive effects between stress and dust mite groups (high vs low) were significantly different for children of atopic vs nonatopic mothers (P for three-way interaction = 0.005). Among children of atopic mothers, the positive association between stress and IgE was stronger in the high dust mite group. In children of mothers without a history of atopy, the positive association between stress and IgE was most evident in the low allergen group. CONCLUSIONS: Prenatal stress was independently associated with elevated cord blood IgE. Mechanisms underlying stress effects on fetal immunomodulation may differ based on maternal atopic status. PMID- 22309646 TI - Molecular links between endometriosis and cancer. AB - Endometriosis is the leading cause of morbidity among premenopausal women affecting about 1 in 10 females. The features shared by endometriosis and cancer include the ability to evade apoptosis, the stem cell-like ability and angiogenic potential. As such characteristics are encoded by the cell's genetic constitution, acquired mutations are responsible for the malignant transformation of endometriosis. Indeed, a number of tumour-suppressor genes and proto oncogenes, such as protein 53 (P53) and B-cell lymphoma 2 (BCL-2) respectively, are mutated and as a result differentially expressed between endometriotic and malignant tissue associated with endometriosis. Moreover, cytokines and macrophages, both of which are inflammatory mediators have been implicated in the transformation process. The angiogenic properties possessed by cancer arising from endometriosis signifies a bad prognosis, while the stem cell-like activity possessed by both endometriosis and cancer has been attributed to the effect of oestrogen. A number of differences between endometriosis and cancer are found at the molecular level. Considering the link between these two pathologies, the three components which fuel the malignant transformation of endometriosis can be embodied in the endometriosis-induced carcinoma (EIC) triangle which shows the intricate relationship between endocrinologic, immunologic and genetic components. PMID- 22309647 TI - Enhanced effects of cigarette smoke extract on inflammatory cytokine expression in IL-1beta-activated human mast cells were inhibited by Baicalein via regulation of the NF-kappaB pathway. AB - BACKGROUND: Human mast cells are capable of a wide variety of inflammatory responses and play a vital role in the pathogenesis of inflammatory diseases such as allergy, asthma, and atherosclerosis. We have reported that cigarette smoke extract (CSE) significantly increased IL-6 and IL-8 production in IL-1beta activated human mast cell line (HMC-1). Baicalein (BAI) has anti-inflammatory properties and inhibits IL-1beta- and TNF-alpha-induced inflammatory cytokine production from HMC-1. The goal of the present study was to examine the effect of BAI on IL-6 and IL-8 production from CSE-treated and IL-1beta-activated HMC-1. METHODS: Main-stream (Ms) and Side-stream (Ss) cigarette smoke were collected onto fiber filters and extracted in RPMI-1640 medium. Two ml of HMC-1 at 1 * 106 cells/mL were cultured with CSE in the presence or absence of IL-1beta (10 ng/mL) for 24 hrs. A group of HMC-1 cells stimulated with both IL-1beta (10 ng/ml) and CSE was also treated with BAI. The expression of IL-6 and IL-8 was assessed by ELISA and RT-PCR. NF-kappaB activation was measured by electrophoretic mobility shift assay (EMSA) and IkappaBalpha degradation by Western blot. RESULTS: Both Ms and Ss CSE significantly increased IL-6 and IL-8 production (p < 0.001) in IL 1beta-activated HMC-1. CSE increased NF-kappaB activation and decreased cytoplasmic IkappaBalpha proteins in IL-1beta-activated HMC-1. BAI (1.8 to 30 MUM) significantly inhibited production of IL-6 and IL-8 in a dose-dependent manner in IL-1beta-activated HMC-1 with the optimal inhibition concentration at 30 MUM, which also significantly inhibited the enhancing effect of CSE on IL-6 and IL-8 production in IL-1beta-activated HMC-1. BAI inhibited NF-kappaB activation and increased cytoplasmic IkappaBalpha proteins in CSE-treated and IL 1beta-activated HMC-1. CONCLUSIONS: Our results showed that CSE significantly increased inflammatory cytokines IL-6 and IL-8 production in IL-1beta-activated HMC-1. It may partially explain why cigarette smoke contributes to lung and cardiovascular diseases. BAI inhibited the production of inflammatory cytokines through inhibition of NF-kappaB activation and IkappaBalpha phosphorylation and degradation. This inhibitory effect of BAI on the expression of inflammatory cytokines induced by CSE suggests its usefulness in the development of novel anti inflammatory therapies. PMID- 22309648 TI - Efficacy of ImageJ in the assessment of apoptosis. AB - OBJECTIVE: To verify the efficacy of ImageJ 1.43 n in determining the extent of apoptosis which is a complex and multistep process. STUDY DESIGN: Cisplatin in different concentrations was used to induce apoptosis in cultured Hep2 cells. Cell viability assay and nuclear image analysis of stained Hep2 cells were used to discriminate apoptotic cells and cells suspected to be undergoing apoptosis from control cells based on parameters such as nuclear area, circularity, perimeter and nuclear area factor (NAF), in association with visual morphology. RESULTS: Image analysis revealed a progressive and highly significant decrease in nuclear area factor detected in apoptotic cells and in cells suspected of undergoing apoptosis compared to the control cells (P-values < 0.01). Some of the other studied parameters showed also the same trend. This decrease was assumed to indicate DNA loss. Image analysis results correlated positively and significantly with the results obtained by cell viability assay (R = 0.958, P-value = 0.042). NAF was the most reliable parameter in assessment of apoptosis. CONCLUSION: Nuclear area factor can be calculated using powerful free and open-source software. Consequently, a quantitative measure of apoptosis can be obtained that is linked to morphological changes. ImageJ 1.43 n may therefore provide a useful tool for the assessment and discrimination of apoptotic cells. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/5929043086367338. PMID- 22309649 TI - Selective enumeration of viable Enterobacteriaceae and Pseudomonas spp. in milk within 7 h by multicolor fluorescence in situ hybridization following microcolony formation. AB - Rapid and simultaneous enumeration of viable Enterobacteriaceae and viable Pseudomonas spp. in milk was achieved by using multicolor fluorescence in situ hybridization (FISH) with oligonucleotide probes based on 16S ribosomal RNA (rRNA) sequences in combination with a microcolony growth method (multicolor microcolony-FISH; MMC-FISH). The procedure of MMC-FISH method is rather simple; that is milk clearing, filtration of cells, incubation, hybridization and enumeration. Enumeration of targeted bacteria in logarithmic growth phase, stationary phase, or in a starved state in milk by MMC-FISH required 5-7 h, while it took 1-3 days to test for Escherichia coli and Pseudomonas putida by the conventional culture method. The numbers of E. coli and P. putida in each phase or in a starved state in milk determined by MMC-FISH were almost the same or greater than the number of colony forming units determined by the plate counting method. The MMC-FISH allows rapid examination of contamination in milk by viable Enterobacteriaceae and Pseudomonas spp. with growth potential. PMID- 22309650 TI - Improvement of the transcriptional strength of baculovirus very late polyhedrin promoter by repeating its untranslated leader sequences and coexpression with the primary transactivator. AB - Modified polyhedrin promoter (Ppolh) was designed by repeating burst sequences (BSs) and adopted to overexpress rat alpha2,6-sialyltransferase (ST6Gal I) in silkworm. Modified Ppolh of five BSs with VLF-1 coexpression yielded 2.9 U/ml ST6Gal I activity and 32.5 mU/mg specific activity, which was 1.7- and 2.3-fold higher, respectively compared to Ppolh. PMID- 22309651 TI - Prevalence of virulent Yersinia enterocolitica in bulk raw milk and retail cheese in northern-west of Iran. AB - To determine the prevalence of virulent Yersinia enterocolitica, 554 samples consisting of 354 bulk raw milks and 200 traditional cheeses were collected from different parts of Eastern-Azerbaijan province, during a 23-month period from 2008 to 2010. The occurrence of virulent strains of Y. enterocolitica in samples enriched in peptone sorbitol bile broth (PSBB) was evaluated via the detection of attachment invasion locus (ail) gene by PCR. The viability of virulent Y. enterocolitica in the PCR-positive samples was tested using conventional culture method and the isolates were confirmed by the second-phase ail-PCR. According to the results, 8.66% of total samples including 7.62% of bulk raw milks and 10.5% of raw milk cheeses were found ail-positive by PCR method; subsequently Y. enterocolitica was isolated by the culture method and confirmed by the second phase ail-PCR in 2.88% of total samples including 2.26% of raw milks and 4% of cheese samples. It was concluded that, a sample enrichment followed by ail-PCR was more sensitive and robust to detect and distinguish the virulent strains of Y. enterocolitica compared to the conventional culture method. PMID- 22309652 TI - Nursing care of the family before and after a death in the ICU--an exploratory pilot study. AB - This qualitative descriptive study was undertaken in two metropolitan ICUs utilising focus groups to describe the ways in which ICU nurses care for the families of dying patients during and after the death. Participants shared their perspectives on how they care for families, their concerns about care, and detailed the strategies they use to provide timely and person-centred family care. Participants identified that their ICU training was inadequate in equipping them to address the complex care needs of families leading up to and following patient deaths, and they relied on peer mentoring and role-modelling to improve their care. Organisational constraints, practices and pressures impacting on the nurse made 'ideal' family care difficult. They also identified that a lack of access to pastoral care and social work after hours contributed to their concerns about family care. Participants reported that they valued the time nurses spent with families, and the importance of ensuring families spent time with the patient, before and after death. PMID- 22309653 TI - Microwave degradation of methyl orange dye in aqueous solution in the presence of nano-TiO2-supported activated carbon (supported-TiO2/AC/MW). AB - In this study, nano-TiO(2)-supported activated carbon (TiO(2)/AC) was developed for the microwave (MW) degradation of an azo dye, methyl orange (MO), selected as a model contaminant in aqueous solution. The effects of selected process parameters such as supported TiO(2) content, MW irradiation time, initial MO concentration, catalyst dose, and solution pH on the degradation were assessed in detail. The results showed that the supported TiO(2) on AC could be excited resulting in the production of hydroxyl radical (OH) in aqueous solution under MW irradiation, which significantly enhanced the performance of AC/MW process for the degradation of MO. Also, the supported-TiO(2)/AC displayed higher catalytic activity than AC alone under MW irradiation. By comparison, the supported TiO(2)/AC/MW process exhibited several advantages, including high degradation rate, short irradiation time, no residual intermediates and no secondary pollution. Hence, it shows to be a promising technology for the destruction of organic contaminants in dye treatment applications. PMID- 22309654 TI - Immobilization of lead in a Korean military shooting range soil using eggshell waste: an integrated mechanistic approach. AB - This study evaluated the effectiveness of eggshell and calcined eggshell on lead (Pb) immobilization in a shooting range soil. Destructive and non-destructive analytical techniques were employed to determine the mechanism of Pb immobilization. The 5% additions of eggshell and calcined eggshell significantly decreased the TCLP-Pb concentration by 68.8% due mainly to increasing soil pH. Eggshell and calcined-eggshell amendments decreased the exchangeable Pb fraction to ~ 1% of the total Pb in the soil, while the carbonate-associated Pb fraction was increased to 40.0-47.1% at >15% application rates. The thermodynamic modeling on Pb speciation in the soil solution predicted the precipitation of Pb-hydroxide [Pb(OH)(2)] in soils amended with eggshell and calcined eggshell. The SEM-EDS, XAFS and elemental dot mapping revealed that Pb in soil amended with calcined eggshell was associated with Si and Ca, and may be immobilized by entrapping into calcium-silicate-hydrate. Comparatively, in the soil amended with eggshell, Pb was immobilized via formation of Pb-hydroxide or lanarkite [Pb(2)O(SO(4))]. Applications of amendments increased activities of alkaline phosphatase up to 3.7 times greater than in the control soil. The use of eggshell amendments may have potential as an integrated remediation strategy that enables Pb immobilization and soil biological restoration in shooting range soils. PMID- 22309655 TI - Interaction of Cd/Zn hyperaccumulating plant (Sedum alfredii) and rhizosphere bacteria on metal uptake and removal of phenanthrene. AB - The effects of bacteria (Burkholderia cepacia) on plant growth, metal uptake, tolerance index and phenanthrene degradation by a hyperaccumulating plant (Sedum alfredii) were investigated. It was found that inoculation of bacteria did not enhance plant growth and metal uptake; while both metal translocation factor (up to 84% for Cd and 42% for Zn) and tolerance index (up to 23.2% for shoot and 72% for root) were significantly increased. In addition, inoculation of bacteria also alleviated the reductions of bioaccumulation factor and phytoextraction efficiency of As, Cu and Zn with the increasing proportions of polluted soil applied, while they were even increased for Cd and Pb (up to 31.2 and 124%, respectively). Up to 96.3% of phenanthrene was removed in the treatment with both plant and bacteria at the end of the experiment. A positive correlation between metal and P accumulation in plants was observed, it is suggested that high P uptake is directly involved in metal detoxification and leading to an increased P requirement. With the assistance of bacteria, S. alfredii could be able to withstand higher metal concentrations and it could also provide a practical tool for phytoremediation. PMID- 22309656 TI - Evaluation of chromium bioaccessibility in chromite ore processing residue using in vitro gastrointestinal method. AB - Incidental ingestion of Chromite ore processing residue (COPR) particles poses a potential health risk. The purpose of this study was to determine the Cr bioaccessibility from COPR using the in vitro gastrointestinal (IVG) procedure. The bioaccessible Cr(VI) was 53.8% and 42.9%, respectively, in the gastric and intestinal phases from a total of 19490 mg kg(-1) Cr(VI) in COPR. Food intake including milk, dough, and ascorbic acid resulted in a significant decrease in Cr(VI) bioaccessibility. Some organic acids such as lactic, malic, and citric acid moderately reduced Cr(VI), while acetic acid exhibited no capacity for Cr(VI) reduction. The integrated area under the concentration-time curve (AUC) of the IVG extraction was used to calculate bioaccessibility. Compared with the bioaccessibility conventionally estimated using concentrations at the end of the extraction (CEP), the AUC technique should be implemented to confirm the accuracy of the IVG method when reduction of Cr(VI) occurs during the extraction. The absence of Cr(VI) phases in extracted residues as evidenced by XANES and XRPD analysis confirmed the Cr(VI) release and Cr(VI) reduction by food and ascorbic acid. With readily bioaccessible Cr(VI) and rapid human uptake, reduction of Cr(VI) might not be as effective a detoxification pathway as initially thought. PMID- 22309657 TI - Development, characterization and in vivo assessment of effective lipidic nanoparticles for dermal delivery of fluconazole against cutaneous candidiasis. AB - The nanoparticulate carrier systems as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have gained interest for the topical treatment of skin associated fungal infection as they facilitate the skin penetration of loaded drugs. Therefore in this study, SLNs and NLCs loaded fluconazole (FLZ) were prepared by solvent diffusion method in an aqueous system and characterized for different parameters. In addition, antifungal activity was carried out on experimentally induced cutaneous candidiasis in immunosuppressed albino rats. The results showed that SLNs and NLCs represent the respective mean particle sizes of approx. 178 and 134 nm with encapsulation efficiency of 75.7+/ 4.94% and 81.4+/-3.89%, respectively. The skin-retention studies of FLZ from in vitro and in vivo experiments revealed significantly higher accumulation of drug in the case of NLCs formulation. The in vivo cumulative amount of FLZ retention from NLCs was more than 5-fold that of the plain solution, while it was 3.3-fold more in the case of an equivalent-dose application in the form of SLNs at 12h after administration. The antifungal study also confirmed the maximum therapeutic efficacy of NLCs, as the lowest number of cfu/ml was recorded. It can be concluded from this study that NLCs provide a good skin targeting effect and may be a promising carrier for topical delivery of FLZ offering the sustained release and maintain the localized effect, resulting in an effective treatment of a life threatening cutaneous fungal infection. PMID- 22309658 TI - Patterns of trunk spine growth in two congeneric species of acanthocephalan: investment in attachment may differ between sexes and species. AB - Acanthocephalans have evolved a hooked proboscis and some taxa have trunk spines to attach to their definitive hosts. These structures are generated before being used, thus a key question is how investment in attachment could optimally be allocated through the ontogeny. The number and arrangement of hooks and spines are never modified in the definitive host, but it is unclear whether these structures grow during adult development. A comparison of the size of trunk spines between cystacanths and adults of Corynosoma cetaceum and C. australe indicated that spines grow in both species, but only in females, which also had significantly larger spines than males. This sexual dimorphism did not result from pure allometry because the body of females was smaller, and did not grow more than that of males. However, having a longer lifespan, females would need to withstand the extreme flow conditions prevailing in marine mammals for longer, inducing different investment and development schedules for spines. Patterns of spine growth also differed between species: fore-trunk spines grew in both species, but hind-trunk spines did only in C. cetaceum. In conclusion, investment strategies on attachment may differ, not only between congeneric species of acanthocephalan, but also between sexes of the same species. PMID- 22309659 TI - Variability between countries in cytokine responses to BCG vaccination: what impact might this have on protection? PMID- 22309660 TI - Hepatitis B vaccination in pregnancy. PMID- 22309662 TI - Targeting EGF receptor variant III: tumor-specific peptide vaccination for malignant gliomas. AB - Glioblastoma multiforme (GBM) is the most common and deadly of the human brain cancers. The EGF receptor is often amplified in GBM and provides a potential therapeutic target. However, targeting the normal receptor is complicated by its nearly ubiquitous and high level of expression in certain tissues. A naturally occurring deletion mutant of the EGF receptor, EGFRvIII, is a constitutively active variant originally identified in a high percentage of brain cancer cases, and more importantly is rarely found in normal tissue. A peptide vaccine, rindopepimut (CDX-110, Celldex Therapeutics), is directed against the novel exon 1-8 junction produced by the EGFRvIII deletion, and it has shown high efficacy in preclinical models. Recent Phase II clinical trials in patients with newly diagnosed GBM have shown EGFRvIII-specific immune responses and significantly increased time to progression and overall survival in those receiving vaccine therapy, as compared with published results for standard of care. Rindopepimut therefore represents a very promising therapy for patients with GBM. PMID- 22309663 TI - Aflunov((r)): a prepandemic influenza vaccine. AB - Influenza viruses are adept in human populations. Indeed, they have the capacity to evade the immune system through mechanisms of mutations (antigenic drift) and major variations in surface protein expression (antigenic shift). When a major change occurs, the risk of a human pandemic arises. Three influenza pandemics occurred during the 20th century, the most serious being the Spanish influenza. The last pandemic of the past century occurred in 1968, and the responsible virus infected an estimated 1-3 million people throughout the world. The first pandemic of the present century occurred in 2009 and was sustained by a H1N1 strain (A/California/07/09). In 1997, a novel avian influenza virus, H5N1, first infected humans in China. Since its emergence, the H5N1 virus has spread from Asia to Europe and Africa, resulting in the infection of millions of poultry and wild birds. So far, 522 human cases and 322 deaths have been reported by the WHO. Many studies have therefore been performed to obtain efficacious and safe H5N1 vaccines. One of these is Aflunov((r)). Aflunov is a prepandemic monovalent A/H5N1 influenza vaccine adjuvanted with MF59 produced by Novartis Vaccines and Diagnostics. In nonclinical studies conducted in rabbits, Aflunov proved to be well-tolerated, did not cause maternal or embryo-fetal toxicity, was not teratogenic, and had no effects on postnatal development. In clinical studies, Aflunov proved safe and well-tolerated in infants, children, adolescents, adults and the elderly. In the same subjects, the vaccine elicited robust immunogenicity against both homologous (A/Vietnam/1194/2004 clade 1) and heterologous viral strains (for instance, A/Indonesia/05/2005 or A/Turkey/15/2006) and induced immunologic memory. Thus, in 2010, the CHMP issued a positive opinion on Aflunov and in January 2011 Aflunov was given marketing authorization. This vaccine could be very useful in the event of adaptation of the H5N1 virus to humans, which could cause a new pandemic. PMID- 22309664 TI - Tailor-made cleavage site attenuates influenza B. AB - Influenza B viruses contribute significantly to human influenza. The circulation of two antigenically divergent lineages of this virus can reduce the efficacy of licensed influenza vaccines. A novel live-attenuated influenza B vaccine candidate has been generated by creating a virus that strictly requires elastase activity for the accurate proteolytic maturation of its hemagglutinin. This mutant influenza B virus grows to high titers in vitro and is strongly attenuated in mice, yet it induces a robust protective immune response in this host. The findings on this tamed influenza B virus and its potential prospects are discussed. PMID- 22309665 TI - A strategy to simultaneously eradicate the natural reservoirs of rabies and Ebola virus. AB - The efficacy of a recombinant live-attenuated or chemically inactivated bivalent vaccine against rabies virus (RABV) and Ebola virus (EBOV) infection was evaluated in a lethal mouse model of infection. The vaccines were derived from the live-attenuated Street Alabama Dufferin B19 RABV platform already approved for veterinary use, where intramuscular, intranasal and intraperitoneal administration of the recombinant vaccines were avirulent in adult mice. Significant levels of serum RABV- and EBOV-specific antibodies were observed postvaccination, with levels that correlated with protection in vaccinated mice post-RABV or -EBOV challenge. These results justify further studies in guinea pigs and nonhuman primates, and highlight a promising strategy to eradicate the natural reservoirs of RABV and EBOV. PMID- 22309666 TI - Immunosenescence and herd immunity: with an ever-increasing aging population do we need to rethink vaccine schedules? AB - Vaccination is a powerful public health tool that has been of tremendous benefit in protecting vulnerable populations from specific infections. Moreover, in addition to the direct benefits to vaccinated individuals, the indirect effects of protection at the community level have also been demonstrated and termed 'herd immunity'. The predicted demographic shift in the population landscape towards an ever-increasing aging population and the evidence suggesting that older individuals produce less-than-optimal vaccine responses have raised the question of rethinking vaccine schedules. This article provides evidence that even if herd immunity might be an option to indirectly protect the aging and aged adult population, the highest priorities for the near future must be to understand how vaccine responses in older individuals can be improved, to break down the public, cultural, societal and political barriers to vaccination and to counter the antivaccination movement that inhibits the worldwide spread of lifelong immunization programs. PMID- 22309667 TI - Feasibility of cross-protective vaccination against flaviviruses of the Japanese encephalitis serocomplex. AB - Serological cross-reactivity providing cross-protective immunity between antigenically related viruses is a cornerstone of vaccination. It was the immunological basis for the first human vaccine against smallpox introduced more than 200 years ago, and continues to underpin modern vaccine development as has recently been shown for human papillomavirus vaccines, which confer cross protection against other oncogenic papillomavirus types not present in the vaccine. Here, we review the feasibility of cross-protective vaccination against an antigenic group of clinically important viruses belonging to the Japanese encephalitis serocomplex in the Flaviviridae family. We will discuss evidence suggesting that 'new generation' flavivirus vaccines may provide effective cross protective immunity against heterologous Japanese encephalitis serocomplex viruses, and appraise potential risks associated with cross-reactive vaccine immunity. The review will also focus on the structural and mechanistic basis for cross-protective immunity among this group of flaviviruses, which is predominantly mediated by antibodies against a single viral surface protein. PMID- 22309669 TI - Remaining issues and challenges for rotavirus vaccine in preventing global childhood diarrheal morbidity and mortality. AB - Rotavirus vaccines have had a dramatic impact on morbidity and mortality from diarrhea among children in high- and middle-income countries that have introduced the vaccine into their national immunization programs. Widespread introduction of rotavirus vaccine in developing countries is imminent and their full potential in reducing the global burden from severe childhood diarrhea may soon be realized. The objectives of this paper are to describe the remaining issues and challenges in ensuring the success of the global rotavirus vaccination program and to discuss further research needed to help address them. PMID- 22309670 TI - Pneumococcal vaccination among adults with chronic respiratory diseases: a historical overview. AB - Streptococcus pneumoniae, the most common cause of community-acquired pneumonia, remains a major cause of morbidity and mortality worldwide. The presence of chronic respiratory illness is a major risk factor for pneumonia, and smoking (the most common cause of chronic obstructive pulmonary disease) is also an important risk factor for pneumonia and invasive pneumococcal disease. There are currently three established approaches to antipneumococcal vaccination: capsular polysaccharide pneumococcal vaccines (recommended for adults and some children at risk), protein-polysaccharide conjugate pneumococcal vaccines (classically recommended for infants and young children and currently under evaluation for adults aged 50 years or older for the prevention of invasive disease) and experimental protein-based pneumococcal vaccines (under investigation in animal models). Although patients with chronic respiratory diseases are commonly described as an at-risk population for pneumococcal infections, studies on pneumococcal vaccination efficacy in such patients are very limited and vaccination effectiveness remains controversial. This paper reviews available data on the efficacy and effectiveness of polysaccharide pneumococcal vaccination among adults with chronic respiratory diseases. PMID- 22309668 TI - Technologies for enhanced efficacy of DNA vaccines. AB - Despite many years of research, human DNA vaccines have yet to fulfill their early promise. Over the past 15 years, multiple generations of DNA vaccines have been developed and tested in preclinical models for prophylactic and therapeutic applications in the areas of infectious disease and cancer, but have failed in the clinic. Thus, while DNA vaccines have achieved successful licensure for veterinary applications, their poor immunogenicity in humans when compared with traditional protein-based vaccines has hindered their progress. Many strategies have been attempted to improve DNA vaccine potency including use of more efficient promoters and codon optimization, addition of traditional or genetic adjuvants, electroporation, intradermal delivery and various prime-boost strategies. This review summarizes these advances in DNA vaccine technologies and attempts to answer the question of when DNA vaccines might eventually be licensed for human use. PMID- 22309671 TI - Pattern recognition receptors: sentinels in innate immunity and targets of new vaccine adjuvants. AB - The innate immune system plays an essential role in the host's first line of defense against microbial invasion, and involves the recognition of distinct pathogen-associated molecular patterns by pattern recognition receptors (PRRs). Activation of PRRs triggers cell signaling leading to the production of proinflammatory cytokines, chemokines and Type 1 interferons, and the induction of antimicrobial and inflammatory responses. These innate responses are also responsible for instructing the development of an appropriate pathogen-specific adaptive immune response. In this review, the focus is on different classes of PRRs that have been identified, including Toll-like receptors, nucleotide-binding oligomerization domain-like receptors, and the retinoic acid-inducible gene-I like receptors, and their importance in host defense against infection. The role of PRR cooperation in generating optimal immune responses required for protective immunity and the potential of targeting PRRs in the development of a new generation of vaccine adjuvants is also discussed. PMID- 22309673 TI - Oxaliplatin as a radiosensitiser for upper and lower gastrointestinal tract malignancies: what have we learned from a decade of translational research? AB - Some of the greatest advances in the treatment of solid malignancies have resulted from the combination of chemotherapy and radiotherapy treatments. This article comprehensively reviews the current clinical evidence for oxaliplatin based chemo-radiotherapy that may improve local control and survival. In order to understand how clinical studies should be designed, the pre-clinical evidence for the use of oxaliplatin chemotherapy as a radiosensitising agent is appraised. Particular focus is placed on oxaliplatin's biological mechanisms of action, including cell cycle effects, the formation of DNA adducts and interstrand cross links and the role of DNA repair proteins. At a clinical level, there is currently no evidence to suggest that oxaliplatin provides an additional benefit to concurrent chemo-radiation regimes that utilise fluoropyrimidines; we evaluate the reasons for this observation, the limitations of clinical trial design and the opportunities that currently exist to design clinical trials which are underpinned by an understanding of the basic biology. PMID- 22309674 TI - beta-Phenethyl isothiocyanate induces death receptor 5 to induce apoptosis in human oral cancer cells via p38. AB - OBJECTIVES: beta-Phenylethyl isothiocyanate (PEITC) has been demonstrated to fight many types of cancers through various molecular pathways. In this study, we focused on its effect on the induction of apoptosis to inhibit cell growth and molecular mechanism in oral cancer. MATERIALS AND METHODS: 3-(4,5-dimethylthiazol 2-yl)-5-(2,4-disulfophenyl)-2-(4 sulfophenyl)-2H-tetrazolium (MTS) assay was used to examine cell viability. The apoptotic effect was investigated using 4'-6 Diamidino-2-phenylindole (DAPI) staining or Western blotting. Inhibitors were used to determine the molecular target and mechanism of PEITC-mediated apoptosis. RESULTS: beta-Phenylethyl isothiocyanate inhibited the growth of HN22 human oral cancer cells and induced caspase-dependent apoptosis in HN22 cells as evidenced by nuclear fragmentation and the activation of caspase 3. It increased cleaved caspase 8, truncated BID, and death receptor 5 (DR5) through the activation of p38 MAPK. This result was confirmed by blockage of PEITC-induced cleavages of Poly(ADP-ribose) Polymerase, caspase-3, caspase-8, and DR5 by p38 MAPK inhibitor, SB203580. We also found that PEITC activated p38 and augmented DR5 to induce apoptosis in other human oral cancer cells. CONCLUSIONS: These results suggest that DR5 is a potential molecular target for PEITC-induced apoptosis in oral cancer via p38 MAPK. PMID- 22309675 TI - Metformin versus lifestyle changes in treating women with polycystic ovary syndrome. AB - OBJECTIVE: To compare the efficacy of metformin with that of lifestyle changes in patients with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized clinical trial of 40 women with PCOS to analyze the effects of metformin and lifestyle intervention treatments on menstrual pattern and hormone and metabolic profile. The duration of treatment was 6 months. Statistical analysis was done using Student's t-test. RESULTS: Fifteen women in the metformin group and 12 in the lifestyle changes group completed the study. The menstrual pattern improved by ~67% in both groups. There was a significant decrease in waist circumference in the lifestyle changes group (101.8 +/- 3.9 and 95.1 +/- 3.6, at baseline and at 6 months of treatment, respectively; p < 0.001) and in body mass index (BMI) in both groups. The predictor of menstrual pattern improvement was BMI. CONCLUSIONS: Both metformin and lifestyle changes may increase the number of menstrual cycles in PCOS. This effect was related to a decrease in BMI. PMID- 22309676 TI - Coexposure of dioxin-like polychlorinated biphenyls and polychlorinated dibenzo-p dioxins and dibenzofurans in free-range hens and implications derived from congener profile analysis. AB - The consumption of free-range eggs is becoming more popular worldwide. We analyzed the levels of 12 dioxin-like polychlorinated biphenyls (dl-PCBs) and their congener profiles from 6 free-range and 12 caged egg samples. The mean levels of dl-PCBs in the free-range samples were 5.4 times higher than those in caged eggs. All egg samples exhibited at least two characteristic dl-PCB congener patterns, which reflected distinctive contamination sources. Additionally, for the first time, we demonstrated that the dl-PCB levels in the free-range eggs were highly correlated with elevated levels of 17 polychlorinated dibenzo-p dioxins and dibenzofurans (PCDD/Fs) (r = 0.986; p < 0.001), indicating a coexposure scenario in free-range hens. Cluster analysis of congener patterns implied that this coexposure scenario could be attributed to distinct dl-PCB and PCDD/F sources. This congener profile information provides insights from a different perspective for further identifying potential dl-PCB and PCDD/F sources in the polluted free-range eggs. PMID- 22309677 TI - Clara cell protein in nasal lavage fluid and nasal nitric oxide - biomarkers with anti-inflammatory properties in allergic rhinitis. AB - BACKGROUND: Clara cell protein (CC16) is ascribed a protective and anti inflammatory role in airway inflammation. Lower levels have been observed in asthmatic subjects as well as in subjects with intermittent allergic rhinitis than in healthy controls. Nasal nitric oxide (nNO) is present in high concentrations in the upper airways, and considered a biomarker with beneficial effects, due to inhibition of bacteria and viruses along with stimulation of ciliary motility. The aim of this study was to evaluate the presumed anti inflammatory effects of nasal CC16 and nNO in subjects with allergic rhinitis. METHODS: The levels of CC16 in nasal lavage fluids, achieved from subjects with persistent allergic rhinitis (n = 13), intermittent allergic rhinitis in an allergen free interval (n = 5) and healthy controls (n = 7), were analyzed by Western blot. The levels of nNO were measured by the subtraction method using NIOX(r). The occurrences of effector cells in allergic inflammation, i.e. metachromatic cells (MC, mast cells and basophiles) and eosinophils (Eos) were analyzed by light microscopy in samples achieved by nasal brushing. RESULTS: The levels of CC16 correlated with nNO levels (r2 = 0.37; p = 0.02) in allergic subjects.The levels of both biomarkers showed inverse relationships with MC occurrence, as higher levels of CC16 (p = 0.03) and nNO (p = 0.05) were found in allergic subjects with no demonstrable MC compared to the levels in subjects with demonstrable MC. Similar relationships, but not reaching significance, were observed between the CC16 and nNO levels and Eos occurrence. The levels of CC16 and nNO did not differ between the allergic and the control groups. CONCLUSIONS: The correlation between nasal CC16 and nNO levels in patients with allergic rhinitis, along with an inverse relationship between their levels and the occurrences of MC in allergic inflammation, may indicate that both biomarkers have anti-inflammatory effects by suppression of cell recruitment. The mechanisms behind these observations warrant further analyses. PMID- 22309678 TI - High accuracy analysis of glucose in human serum by isotope dilution liquid chromatography-tandem mass spectrometry. AB - BACKGROUND: An isotope dilution mass spectrometry (IDMS) technique has been developed for high accuracy analysis of glucose in human serum. Currently, all the IDMS methods for glucose analysis are based on gas chromatography-mass spectrometry (GC-MS). In this study, isotope dilution liquid chromatography tandem mass spectrometry (ID LC-MS/MS) was investigated. METHODS: NIST SRM 965b glucose in frozen human serum was analyzed by linear regression IDMS based on both LC-MS/MS and GC-MS. Serum samples were spiked with isotope labeled glucose and deproteinized by acetonitrile. For LC-MS/MS measurement, the supernate was injected directly after filtration and dilution. For GC-MS measurement, the supernate was evaporated to dryness and went through a two-step derivatization before injection. RESULTS: All measurements had good precision with CVs of <1%. Results from GC-MS agreed very well with results from LC-MS/MS, with a difference of <0.7%. The final reporting values in this study, based solely on LC-MS/MS, were within the certified ranges. The relative expanded uncertainties were within the range of 1.37% to 1.69% for the 4 levels of glucose, which were comparable with uncertainties from the certificate. CONCLUSIONS: The IDMS method based on LC MS/MS is precise and accurate. It does not require lengthy derivatization steps and thus, greatly simplifies the sample preparation procedure. PMID- 22309679 TI - Significant association of past parvovirus B19 infection with cytopenia in both adult-onset Still's disease and systemic lupus erythematosus patients. AB - BACKGROUND: Human parvovirus B19 (B19) infection has been reported as a possible cause of autoimmune diseases. The association of B19 infection with adult-onset Still's diseases (AOSD) remains unclear. METHODS: IgM and IgG against B19-VP1/2 were determined using ELISA in 86 patients with AOSD, 58 patients with systemic lupus erythematosus (SLE) and 64 healthy controls. Anti-B19-VP1-unique region (VP1u) and anti-B19-nonstructural protein-1(NS1) antibodies were assessed by Western blot. B19 DNA was detected by nested PCR. RESULTS: Forty-three (50.0%) of 86 AOSD patients, 27 (46.6%) of 58 SLE patients and 30 (46.9%) of 64 controls had positivity for anti-B19-VP1/2-IgG in the absence of anti-B19-VP1/2-IgM, indicating past infection. None of enrolled subjects had detectable circulating B19 DNA. Significantly higher positivity rates for anti-B19-VP1u and anti-B19-NS1 IgG were observed in AOSD patients (39.5% and 46.5% respectively) and SLE patients (34.5% and 36.2% respectively) than in healthy controls (14.1%, p<0.005 for AOSD and p<0.05 for SLE, and 15.6%, p<0.001 for AOSD and p<0.05 for SLE; respectively). AOSD patients and SLE patients with seropositive results for anti B19-VP1/2 IgG, anti-B19-VP1u or anti-B19-NS1 antibodies had a higher frequency of leucopenia and thrombocytopenia when compared to those with seronegative results. AOSD patients with anti-B19-VP1u or anti-B19-NS1 antibodies were more likely to have arthritis in comparison with those without these antibodies. CONCLUSIONS: Higher seroreactivity for anti-B19-VP1u and anti-B19-NS1 IgG were associated with cytopenia in both AOSD and SLE patients with unique correlation to arthritis in the AOSD. Further studies are necessary to determine if these responses correlate with a common genetic risk in patients with AOSD and SLE. PMID- 22309680 TI - Discrimination between malignant and benign ovarian tumors by plasma metabolomic profiling using ultra performance liquid chromatography/mass spectrometry. AB - BACKGROUND: Discrimination between epithelial ovarian cancer (EOC) and benign ovarian tumor (BOT) has always been difficult in clinical practice. We investigated the application of metabolomics in distinguishing EOC and BOT and tried to discover valuable biomarkers. METHODS: Plasma metabolomic profiling was performed using ultra-performance liquid chromatography mass spectrometry (UPLC/MS). Partial least-squares discriminant analysis was employed to classify EOC and BOT, and reveal their metabolic differences. The area under the receiver operating characteristic curve (AUC) was utilized to evaluate the predictive performance of the metabolic profiles for external validation set. RESULTS: The metabolomic profiles consisting of 535 metabolites revealed a clear separation between EOC and BOT, with AUC of 0.86 for the external validation set. 6 metabolic biomarkers were identified, and the plasma concentrations of the 4 ascertained biomarkers (L-tryptophan, LysoPC(18:3), LysoPC(14:0), and 2 Piperidinone) were lower in EOC patients than those in BOT patients. Among them, tryptophan and LysoPC have been suspected to participate in cancer progression, and 2-Piperidinone might be a novel biomarker for EOC. CONCLUSIONS: Metabolomics could be used to discriminate EOC from BOT in clinical practice, and the identified metabolic biomarkers might be important on investigating the biological mechanisms of EOC. PMID- 22309681 TI - CD163 and its expanding functional repertoire. AB - Macrophages are key players of the immune system and express a variety of surface receptors. CD163 is one such receptor which belongs to the scavenger receptor cysteine-rich super family (SRCR-SF) class B. It has four isoforms which differ in the structure of their cytoplasmic domains and putative phosphorylation sites. Expression of CD163 is tightly regulated with a general tendency of anti inflammatory signals to induce its synthesis, while pro-inflammatory signals downregulate its expression. Previously the molecule has been shown to act as a receptor for hemoglobin-haptoglobin complexes. However, it also plays a crucial role in the control of inflammatory processes by induction of anti-inflammatory pathways. Soluble CD163, which is generated via ectodomain shedding, serves as a potential diagnostic tool in a variety of disease states, such as inflammation, atherosclerosis, transplant rejection and carcinoma. Recently, CD163 has been identified as a promising target for cell directed therapy. In this review we aim to summarize the current knowledge of CD163. PMID- 22309682 TI - Effects of chronic estradiol or testosterone treatment upon sexual behavior in sexually sluggish male rats. AB - Sexually sluggish (SS) male rats represent a small proportion of animals that take a long time to ejaculate, or sometimes they do not ejaculate, when tested on repeated occasions with sexually receptive females. The current study was done in order to evaluate whether chronic estradiol (E(2)) or testosterone (T) treatment could induce consistent ejaculatory behavior in these male rats. Those males that displayed sexual behavior but did not ejaculate in at least four of five tests were classified as SS and included in the present experiment. They were implanted subcutaneously with Silastic capsules that were empty or filled with E(2) or T. Starting one week after the implant, subjects were tested weekly with sexually receptive females for seven consecutive weeks. At the end of the experiment all subjects were weighed and sacrificed to weigh the accessory sex glands. The results showed that SS males implanted with an empty or T-filled capsule remained as such; they displayed mounts and intromissions but not a consistent pattern of ejaculation despite the twelve weeks of testing (5 screening tests and 7 with the corresponding implant). In contrast, the percentage of SS males implanted with an E(2) capsule that displayed the ejaculatory pattern was significantly reduced. Subjects treated with E(2) also displayed a higher number of mounts than the empty capsule group during several weeks of testing. At the end of the experiment the weights of the body, testicles, epididymis, seminal vesicles, and prostate of the SS male rats chronically treated with E(2) were lower than those of the empty or T capsule groups. In addition, male rats with a T implant showed lower testicular weight than the empty capsule group. These results suggest that the lack of ejaculation patter in SS male rats is not due to estrogenic or androgenic alteration. PMID- 22309684 TI - Update on field use of the available drugs for the chemotherapy of human African trypanosomiasis. AB - Despite the fact that eflornithine was considered as the safer drug to treat human African trypanosomiasis (HAT) and has been freely available since 2001, the difficulties in logistics and cost burden associated with this drug meant that the toxic melarsoprol remained the drug of choice. The World Health Organization responded to the situation by designing a medical kit containing all the materials needed to use eflornithine, and by implementing a training and drugs distribution programme which has allowed a transition to this much safer treatment. The introduction of the combination of nifurtimox and eflornithine (NECT) has accelerated the shift from melarsoprol to the best treatment available, due to reduced dosage and treatment time for eflornithine that has significantly lessened the cost and improved the burden of logistics encountered during treatment and distribution. The decrease in the use of more dangerous but cheaper melarsoprol has meant a rise in the per patient cost of treating HAT. Although NECT is cheaper than eflornithine monotherapy, an unexpected consequence has been a continuing rise in the per patient cost of treating HAT. The ethical decision of shifting to the best available treatment imposes a financial burden on HAT control programmes that might render long-term application unsustainable. These factors call for continuing research to provide new safer and more effective drugs that are simple to administer and cheaper when compared to current drugs. PMID- 22309683 TI - Identification of the NLS and NES motifs of VP2 from chicken anemia virus and the interaction of VP2 with mini-chromosome maintenance protein 3. AB - BACKGROUND: VP2 of chicken anemia virus (CAV) is a dual-specificity phosphatase required for virus infection, assembly and replication. The functions of the nuclear localization signal (NLS) and nuclear export signal (NES) of VP2 in the cell, however, are poorly understood. Our study identified the presence of a NLS in VP2 and showed that the protein interacted significantly with mini-chromosome maintenance protein 3 (MCM3) in the cell. RESULTS: An arginine-lysine rich NLS could be predicted by software and spanned from amino acids 133 to 138 of VP2. The critical amino acids residues between positions 136 and 138, and either residue 133 or 134 are important for nuclear import in mammalian cells based on systematic mutagenesis. A NES is also predicted in VP2; however the results suggest that no functional NES is present and that this protein is CRM1 independent. It was also shown that VP2 is a chromatin binding protein and, notably, using a co-immunoprecipitation assay, it was found that VP2 association with MCM3 and that this interaction does not require DSP activity. CONCLUSIONS: VP2 contains a NLS that span from amino acids 133 to 138. VP2 is a CRM1 independent protein during nuclear export and associates with MCM3 in cells. PMID- 22309685 TI - Cytotoxic effects exerted by Tritrichomonas foetus pseudocysts. AB - The protozoan parasite Tritrichomonas foetus displays a pear-shaped form and a pseudocyst stage. However, little is known about the biology of the pseudocyst. The aim of this work was to assess whether pseudocysts exert cytotoxic effects during their interaction with MDCK cells (an epithelial kidney canine cell line) and compare their behavior to that of the pear-shaped parasites. Pseudocysts and pear-shaped parasites from both cultured and freshly isolated T. foetus were used. Electron microscopy revealed that the epithelial cells exhibited more signs of injury, such as depletion of microvilli, retraction from neighboring cells and swollen mitochondria with loss of electron density in the matrix, when the pseudocysts were used in interaction experiments. In addition, during the co incubation with MDCK cells, pseudocysts exhibited a more intense amoeboid transformation than that found in pear-shaped parasites. The MTT viability assay demonstrated that the pseudocysts were more cytotoxic when in contact with host cells as compared to the flagellated pear-shaped parasites. The JC-1 viability assay revealed that pseudocysts induced a higher loss of mitochondrial membrane potential compared to pear-shaped parasites. Pseudocysts undergoing a budding process were observed after 2.5h of co-incubation with MDCK cells. Our results suggest that the T. foetus pseudocyst might be a more aggressive form. PMID- 22309686 TI - A case of a naturally conceived pregnancy associated with multiple ovarian cysts in a patient with severe untreated primary hypothyroidism. AB - There are few reports of multiple ovarian cysts secondary to hypothyroidism, and multiple ovarian cysts associated with pregnancy most commonly occur in association with assisted reproductive technologies. Herein, we report a case of a naturally conceived pregnancy occurring 2 years after stopping treatment for primary hypothyroidism. The patient developed multiple ovarian cysts in the first trimester, and laboratory studies and ultrasonography were consistent with hypothyroidism. Herein, we present the case and discuss the importance of prenatal screening for hypothyroidism. PMID- 22309692 TI - Detection of MMP-2 and MMP-9 activity in vivo with a triple-helical peptide optical probe. AB - We report a novel activatable NIR fluorescent probe for in vivo detection of cancer-related matrix metalloproteinase (MMP) activity. The probe is based on a triple-helical peptide substrate (THP) with high specificity for MMP-2 and MMP-9 relative to other members of the MMP family. MMP-2 and MMP-9 (also known as gelatinases) are specifically associated with cancer cell invasion and cancer related angiogenesis. At the center of each 5 kDa peptide strand is a gelatinase sensitive sequence flanked by 2 Lys residues conjugated with NIR fluorescent dyes. Upon self-assembly of the triple-helical structure, the 3 peptide chains intertwine, bringing the fluorophores into close proximity and reducing fluorescence via quenching. Upon enzymatic cleavage of the triple-helical peptide, 6 labeled peptide chains are released, resulting in an amplified fluorescent signal. The fluorescence yield of the probe increases 3.8-fold upon activation. Kinetic analysis showed a rate of LS276-THP hydrolysis by MMP-2 (k(cat)/K(M) = 30,000 s(-1) M(-1)) similar to that of MMP-2 catalysis of an analogous fluorogenic THP. Administration of LS276-THP to mice bearing a human fibrosarcoma xenografted tumor resulted in a tumor fluorescence signal more than 5-fold greater than that of muscle. This signal enhancement was reduced by treatment with the MMP inhibitor Ilomostat, indicating that the observed tumor fluorescence was indeed enzyme mediated. These results are the first to demonstrate that triple-helical peptides are suitable for highly specific in vivo detection of tumor-related MMP-2 and MMP-9 activity. PMID- 22309693 TI - Effects of estrogen depletion on angiogenesis in estrogen-receptor-positive breast carcinoma--an immunohistochemical study of vasohibin-1 and CD31 with correlation to pathobiological response of the patients in neoadjuvant aromatase inhibitor therapy. AB - OBJECTIVES: Tumor-stroma interactions, including angiogenesis, are pivotal in breast cancer. Changes of angiogenesis during endocrine therapy have not been reported in breast cancer patients. Vasohibin-1 (VASH-1) is a recently identified endothelium-derived negative feedback regulator of angiogenesis. Vasohibin-1 positive ratio (VPR) is proposed as an indicator of neovascularization of the tissues. METHODS: The status of neovascularization, based on VPR before and after steroidal aromatase inhibitor (AI) exemestane (EXE) treatment, was evaluated in 54 post-menopausal Asian patients. VPR changes were correlated with the pathobiological response of the patients using Ki67 labeling index (LI) changes. RESULTS: When using a decrement of more than 40% in post-treatment Ki67 LI as the definition of response, significant inverse correlation was detected between Ki67 LI and VPR changes in responders. Significant increment in neovascularization, as demonstrated by elevated VPR, was only detected in responders (p = 0.039). Increased angiogenesis detected in responders to neoadjuvant therapy may represent a stromal response to dying/dead cells, as part of tumor-stroma interaction following estrogen depletion. CONCLUSIONS: VPR could be a potential surrogate marker for predicting neoadjuvant endocrine therapy response, incorporating features of both carcinoma and stromal cells, in the early stage of neoadjuvant endocrine therapy before any discernible clinical and/or histopathological changes became apparent. PMID- 22309694 TI - Interleukin 6, soluble tumor necrosis factor receptor I and red blood cell distribution width as biological markers of functional dependence in an elderly population: a translational approach. AB - In the present investigation we have analyzed the association between functional dependence and inflammatory biomarkers using the Barthel Index (BI) and the Katz Index (KI). This analysis may contribute to translational medicine by incorporating the clinical and laboratory data to better understand the relationship between chronic inflammation and functional dependence in the elderly population. The ultimate goal of this study was to identify possible useful biomarkers of functional dependence in the elderly. Participants in this study consisted of 120 older subjects (90 women and 30 men; range 68-105 years) who were selected from the Santa Teresa nursing home (Oviedo, Spain). We studied functional status using the following tools to diagnose the functional dependence by clinicians: BI and KI for activities of daily living. We analyzed morbidity, sociodemographic characteristics and a panel of inflammatory and inflammatory related markers. In linear regression models adjusted by age, sex, anti inflammatory drug use and morbid conditions high levels of interleukin 6 (IL-6) and soluble TNF receptor-I (sTNF-RI) were associated with functional dependence as measured using BI and KI. Elevated levels of red blood cell distribution width (RDW) were also associated with functional dependence measured using the KI after adjusting for the same potential confounders. The current results suggest that high IL-6, sTNF-RI and RDW levels are associated with the functional dependence in the elderly population. The results are consistent with the presumed underlying biological mechanism, in which the up-regulation of inflammatory mediators is associated with functional dependence in elderly subjects. PMID- 22309695 TI - A direct detection of Escherichia coli genomic DNA using gold nanoprobes. AB - BACKGROUND: In situation like diagnosis of clinical and forensic samples there exists a need for highly sensitive, rapid and specific DNA detection methods. Though conventional DNA amplification using PCR can provide fast results, it is not widely practised in diagnostic laboratories partially because it requires skilled personnel and expensive equipment. To overcome these limitations nanoparticles have been explored as signalling probes for ultrasensitive DNA detection that can be used in field applications. Among the nanomaterials, gold nanoparticles (AuNPs) have been extensively used mainly because of its optical property and ability to get functionalized with a variety of biomolecules. RESULTS: We report a protocol for the use of gold nanoparticles functionalized with single stranded oligonucleotide (AuNP- oligo probe) as visual detection probes for rapid and specific detection of Escherichia coli. The AuNP- oligo probe on hybridization with target DNA containing complementary sequences remains red whereas test samples without complementary DNA sequences to the probe turns purple due to acid induced aggregation of AuNP- oligo probes. The color change of the solution is observed visually by naked eye demonstrating direct and rapid detection of the pathogenic Escherichia coli from its genomic DNA without the need for PCR amplification. The limit of detection was ~54 ng for unamplified genomic DNA. The method requires less than 30 minutes to complete after genomic DNA extraction. However, by using unamplified enzymatic digested genomic DNA, the detection limit of 11.4 ng was attained. Results of UV-Vis spectroscopic measurement and AFM imaging further support the hypothesis of aggregation based visual discrimination. To elucidate its utility in medical diagnostic, the assay was validated on clinical strains of pathogenic Escherichia coli obtained from local hospitals and spiked urine samples. It was found to be 100% sensitive and proves to be highly specific without any cross reaction with non-Escherichia coli strains. CONCLUSION: This work gives entry into a new class of DNA/gold nanoparticles hybrid materials which might have optical property that can be controlled for application in diagnostics. We note that it should be possible to extend this strategy easily for developing new types of DNA biosensor for point of care detection. The salient feature of this approach includes low-cost, robust reagents and simple colorimetric detection of pathogen. PMID- 22309696 TI - Cognitive "babyness": developmental differences in the power of young children's supernatural thinking to influence positive and negative affect. AB - Perceptions of maturational status may play an important role in facilitating caretaking and resources toward children expressing them. Previous work has revealed evidence that cues of cognitive immaturity foster positive perceptions in adults toward young children at a time during their lives when they are most dependent on adult care. In the current series of studies, the authors investigated when during development these biases emerge. They tested American and Spanish adolescents ranging from 10 to 17 years of age. Each participant rated a series of vignettes presenting different expressions of immature and mature thinking attributed to young children. Results revealed that older adolescents performed similarly to adults tested in previous studies (D. F. Bjorklund, C. Hernandez Blasi, & V. A. Periss, 2010), rating positively expressions of supernatural thinking (e.g., animism) compared with other forms of immature cognition labeled as natural (e.g., overestimation). Both male and female participants 14 years and older favored children expressing the immature supernatural cognition on traits reflecting positive affect (e.g., endearing, likeable), while associating greater negative affect (e.g., sneaky, impatient with) with children expressing immature natural cognition. However, younger adolescents consistently rated all forms of immature thinking less positively than mature thinking, suggesting that a positive bias for some forms of immature thinking develops during adolescence. Based on an evolutionary developmental framework, the authors suggest that supernatural thinking may have a unique role in humans, fostering positive perceptions of young children in older adolescents (and adults) as they prepare themselves for the possible role of parenthood. PMID- 22309697 TI - Enantioselective residue dissipation of hexaconazole in cucumber (Cucumis sativus L.), head cabbage (Brassica oleracea L. var. caulorapa DC.), and soils. AB - In this study, the enantioselective dissipation behavior of hexaconazole was investigated in cucumber fruit, head cabbage, and two different types of agricultural soils. The dissipation kinetics was determined by reverse-phase liquid chromatography-tandem mass spectrometry on a cellulose tris (3-chloro-4 methylphenylcarbamate) chiral column. Dissipation rates of hexaconazole enantiomers followed first-order kinetics; the residues of (+)-enantiomer decreased more rapidly than (-)-enantiomer in cucumber and head cabbage, resulting in relative enrichment of the (-)-form, while the two enantiomers showed similar degradation rates in the tested soils. These results indicate substantial enantioselectivity in the residue dissipation of hexaconazole enantiomers in cucumber and head cabbage; however, nonenantioselective dissipation was observed in the tested soils. PMID- 22309698 TI - Fish oil fortification of soft goat cheese. AB - Soft goat cheese was fortified with four levels of purified fish oil (0, 60, 80, and 100 g fish oil per 3600 g goat milk) prior to curd formation to deliver high levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per serving. The cheese was evaluated for proximate composition, EPA+DHA content, oxidative stability, color, pH, and consumer acceptability. The cheese was partially vacuum packed and stored at 2 degrees C for four weeks. The fat content was significantly (p < 0.05) higher in the fortified treatments compared to the control, but was not significantly different among fortified treatments. Likewise, EPA+DHA contents were not significantly different among fortified samples, averaging 127 mg EPA+DHA per 28 g serving. No significant lipid oxidation was detected by thiobarbituric acid reactive substances (TBARS) or hexanal and propanal headspace analyses over the four week refrigerated shelf life study for any treatments. The fortified cheeses were all liked 'moderately' by consumers (n = 105) for overall acceptability, although the 60 g fortification level did rate significantly higher. The control cheese and the 60 g fortification level had no significant differences in consumer purchase intent. These results demonstrate that fortification levels of up to 127 mg EPA+DHA per serving may be added to soft cheese without negatively affecting shelf-life or consumer purchase intent. PRACTICAL APPLICATION: Omega-3 fatty acids have been shown to have strong associations with health and well-being, and fish oil is a rich source of these fatty acids. In this study, goat cheese was successfully fortified to deliver 127 mg omega-3 fatty acids per 28 g serving without affecting shelf life or consumer purchase intent. PMID- 22309699 TI - Polo-like kinase 1 (Plk1): an Unexpected Player in DNA Replication. AB - Regulation of cell cycle progression is important for the maintenance of genome integrity, and Polo-like kinases (Plks) have been identified as key regulators of this process. It is well established that Polo-like kinase 1 (Plk1) plays critical roles in mitosis but little is known about its functions at other stages of the cell cycle. Here we summarize the functions of Plk1 during DNA replication, focusing on the molecular events related to Origin Recognition Complex (ORC), the complex that is essential for the initiation of DNA replication. Within the context of Plk1 phosphorylation of Orc2, we also emphasize regulation of Orc2 in different organisms. This review is intended to provide some insight into how Plk1 coordinates DNA replication in S phase with chromosome segregation in mitosis, and orchestrates the cell cycle as a whole. PMID- 22309700 TI - Exploring factors relevant in the assessment of the return-to-work process of employees on long-term sickness absence due to a depressive disorder: a focus group study. AB - BACKGROUND: Efforts undertaken during the Return-to-Work (RTW) process need to be sufficient in order to optimize the quality of the RTW process. The purpose of this study was to explore factors relevant to Return-to-Work Effort Sufficiency (RTW-ES) in cases of sick-listed employees with a Depressive Disorder (DD). METHOD: A case of a long-term sick-listed employee with a DD applying for disability benefits was used to gather arguments and grounds relevant to the assessment of RTW-ES. Two focus group meetings were held, consisting of Labor Experts working at the Dutch Social Insurance Institute. Factors were collected and categorized using the International Classification of Functioning, Disability and Health (ICF model). RESULTS: Sixteen factors relevant to RTW-ES assessment in a case of DD were found, categorized in the ICF-model under activities (e.g. functional capacity), personal (e.g. competencies, attitude) and environmental domain (e.g. employer-employee relationship), or categorized under interventions, job accommodations and measures. CONCLUSIONS: This study shows that 16 factors are relevant in the assessment of RTW-ES in employees sick-listed due to DD. Further research is necessary to expand this knowledge to other health conditions, and to investigate the impact of these results on the quality of the RTW-ES assessment. PMID- 22309702 TI - In vitro activity of the F-6 fraction of oregano against Giardia intestinalis. AB - Giardiosis is a neglected parasitic disease that produces diarrhoea and different degrees of malabsorption in humans and animals. Its treatment is based on derivatives of 5-nitroimidazoles, benzimidazoles, nitrofuranes, acridine and nitrotiazoles. These drugs produce undesirable secondary effects, ranging from a metallic taste in the mouth to genetic damage and the selection of resistant strains; therefore, it is necessary to develop new therapeutic alternatives. We demonstrated that a 2-h treatment with 2.87 MUg ml(-1) of fraction 6 of Lippia graveolens (F-6) was sufficient to kill half of an experimental Giardia intestinalis (Syn. G. duodenalis, G. lamblia) population, based on the reduction of MTT-tetrazolium salt levels. F-6 breaks the nuclear envelope and injures the ventral suckling disc. The major compounds of F-6 were characterized as naringenin, thymol, pinocembrin and traces of compounds not yet identified. The results suggest that Lippia is a potential source to obtain compounds with anti Giardia activity. This knowledge is an important starting point to develop new anti-giardial drugs. Future studies will be required to establish the efficacy of F-6 in vivo using an animal model. PMID- 22309703 TI - The larval abdomen of the enigmatic Nannochoristidae (Mecoptera, Insecta). AB - External and internal structures of the larval abdomen of Nannochorista are described in detail, with emphasis on the posterior segments. The results are compared with conditions found in other groups of Antliophora, especially the mecopteran subgroups Boreidae and Pistillifera. Like the entire postcephalic body, the larval abdomen of Nannochorista is extremely slender and nearly cylindrical. The anterior segments are largely unmodified. The surface is smooth and lacks any protuberances or prolegs. The term "cloaca" for the posterior membranous pouch of Nannochorista sp. is morphologically unjustified. A list of muscles of segments IX and X is presented. The abdominal musculature was partly homologized following Snodgrass. The muscles of segment X are highly modified. They move the membranous pouch, the anal papillae, and the terminal lobes. The presence of these structures is likely an adaptation to the specific aquatic life style of nannochoristid larvae. The anal papillae are possibly homologous to the 4-lobed terminal attachment apparatus of larvae of Caurinus (Boreidae) and Pistillifera (Panorpidae, Bittacidae, Choristidae) but this is uncertain. The specific condition in both groups, i.e. two retractile papillae with tracheae and Malpighian tubules in Nannochoristidae, and a 4-lobed exposed attachment device in Pistillifera + Boreidae (groundplan) are very likely autapomorphic for both groups, respectively. A slender abdomen with smooth surface is very likely plesiomorphic within Antliophora and Mecopterida. This condition is found in Trichoptera (partim), Nannochoristidae, Siphonaptera, and many basal groups of Diptera. An eruciform or scarabaeiform body shape with a soft, largely unsclerotised cuticle is probably a synapomorphy of Boreidae and Pistillifera. The presence of ventral protuberances resembling prolegs on the anterior segments is an autapomorphy of the latter group. The homology of paired or unpaired terminal appendages of segment X is uncertain. However, the specific condition of paired and 3-segmented appendages with hooks in Nannochoristidae is almost certainly autapomorphic for this family. The protracted opening of the hind gut on the membranous pouch is another potential autapomorphy of Nannochoristidae. Aquatic habits of larvae, also very likely an apomorphic condition, have likely evolved several times independently in Antliophora. PMID- 22309704 TI - Visual fields and eye morphology support color vision in a color-changing crab spider. AB - Vision plays a major role in many spiders, being involved in prey hunting, orientation or substrate choice, among others. In Misumena vatia, which experiences morphological color changes, vision has been reported to be involved in substrate color matching. Electrophysiological evidence reveals that at least two types of photoreceptors are present in this species, but these data are not backed up by morphological evidence. This work analyzes the functional structure of the eyes of this spider and relates it to its color-changing abilities. A broad superposition of the visual field of the different eyes was observed, even between binocular regions of principal and secondary eyes. The frontal space is simultaneously analyzed by four eyes. This superposition supports the integration of the visual information provided by the different eye types. The mobile retina of the principal eyes of this spider is organized in three layers of three different types of rhabdoms. The third and deepest layer is composed by just one large rhabdom surrounded by dark screening pigments that limit the light entry. The three pairs of secondary eyes have all a single layer of rhabdoms. Our findings provide strong support for an involvement of the visual system in color matching in this spider. PMID- 22309705 TI - Indian hedgehog signaling is required for proper formation, maintenance and migration of Xenopus neural crest. AB - Neural crest induction is the result of the combined action at the neural plate border of FGF, BMP, and Wnt signals from the neural plate, mesoderm and nonneural ectoderm. In this work we show that the expression of Indian hedgehog (Ihh, formerly named Banded hedgehog) and members of the Hedgehog pathway occurs at the prospective neural fold, in the premigratory and migratory neural crest. We performed a functional analysis that revealed the requirement of Ihh signaling in neural crest development. During the early steps of neural crest induction loss of function experiments with antisense morpholino or locally grafted cyclopamine loaded beads suppressed the expression of early neural crest markers concomitant with the increase in neural and epidermal markers. We showed that changes in Ihh activity produced no alterations in either cell proliferation or apoptosis, suggesting that this signal involves cell fate decisions. A temporal analysis showed that Hedgehog is continuously required not only in the early and late specification but also during the migration of the neural crest. We also established that the mesodermal source of Ihh is important to maintain specification and also to support the migratory process. By a combination of embryological and molecular approaches our results demonstrated that Ihh signaling drives in the migration of neural crest cells by autocrine or paracrine mechanisms. Finally, the abrogation of Ihh signaling strongly affected only the formation of cartilages derived from the neural crest, while no effects were observed on melanocytes. Taken together, our results provide insights into the role of the Ihh cell signaling pathway during the early steps of neural crest development. PMID- 22309706 TI - Maternally localized germ plasm mRNAs and germ cell/stem cell formation in the cnidarian Clytia. AB - The separation of the germ line from the soma is a classic concept in animal biology, and depending on species is thought to involve fate determination either by maternally localized germ plasm ("preformation" or "maternal inheritance") or by inductive signaling (classically termed "epigenesis" or "zygotic induction"). The latter mechanism is generally considered to operate in non-bilaterian organisms such as cnidarians and sponges, in which germ cell fate is determined at adult stages from multipotent stem cells. We have found in the hydrozoan cnidarian Clytia hemisphaerica that the multipotent "interstitial" cells (i cells) in larvae and adult medusae, from which germ cells derive, express a set of conserved germ cell markers: Vasa, Nanos1, Piwi and PL10. In situ hybridization analyses unexpectedly revealed maternal mRNAs for all these genes highly concentrated in a germ plasm-like region at the egg animal pole and inherited by the i-cell lineage, strongly suggesting i-cell fate determination by inheritance of animal-localized factors. On the other hand, experimental tests showed that i-cells can form by epigenetic mechanisms in Clytia, since larvae derived from both animal and vegetal blastomeres separated during cleavage stages developed equivalent i-cell populations. Thus Clytia embryos appear to have maternal germ plasm inherited by i-cells but also the potential to form these cells by zygotic induction. Reassessment of available data indicates that maternally localized germ plasm molecular components were plausibly present in the common cnidarian/bilaterian ancestor, but that their role may not have been strictly deterministic. PMID- 22309707 TI - Atypical facial pain related to apical fenestration and overfilling. AB - AIM: To report a case of apical fenestration and overfilling in which unusual pain characteristics made differential diagnosis challenging. SUMMARY: A 32-year old woman with diffuse, spontaneous, moderate pain in the maxillary left posterior sector, exacerbated by masticatory and facial muscle movement, with intense sporadic electric-shooting pain, underwent clinical examination and 3D cone beam computed tomography (CBCT). Apical fenestration with protrusion of the mesial root of tooth 26 beyond the buccal cortical plate, extrusion of canal filling material into the soft tissues and a periosteal reaction were detected. Surgery was performed under the operating microscope. The filling material and surrounding fibrous tissue were located, dissected from healthy soft tissues and removed. The mesiobuccal root apex was resected with a bur to within the bony crypt. A root end was prepared and filled with Tech Biosealer RootEndTM (Isasan, Como, Italy). At the 2-week recall, the patient had complete resolution of the symptoms and good soft-tissue healing. The 1-year recall examination and intra oral radiography confirmed complete resolution of the symptoms and health of periradicular tissues. KEY LEARNING POINTS: Apical fenestration may occur in 9% of cases and may be considered an anatomic predisposing factor for persistent pain after root canal treatment. This complication provides a considerable differential diagnostic challenge and is often misdiagnosed and mistreated. When correctly diagnosed through an accurate, multidisciplinary approach, it may be managed with a simple surgical procedure in which the endodontist should play a key role. Misdiagnosis and over treatment of apical fenestration, through the surgical management of chronic facial pain conditions, could lead to severe exacerbation of chronic pain, which may potentially become persistent or, indeed, intractable. PMID- 22309708 TI - Molecular epidemiology of norovirus in Edinburgh healthcare facilities, Scotland 2007-2011. AB - Norovirus (NoV) is a leading cause of outbreaks of gastroenteritis worldwide, and a major burden for healthcare facilities. This study investigated the NoV genotypes responsible for outbreaks in Edinburgh healthcare facilities between June 2008 and July 2011, and studied their temporal distribution to enable a better understanding of the epidemiology of the outbreaks. A total of 287 samples positive for NoV genogroup II (GII) RNA by reverse transcription-polymerase chain reaction (RT-PCR) during routine diagnostic testing were investigated. Nested RT PCR (nRT-PCR) and sequencing was used to genotype the NoV strains. Overall, a total of 69 NoV strains belonging to six different genoclusters (GII.1, GII.2, GII.3, GII.4, GII.6, GII.13) were detected. The predominant genotype was GII.4 that included four variants, GII.4 2006a, GII.4 2006b, GII.4 2007 and GII.4 2010. Importantly, increases in NoV activity coincided with the emergence of new GII.4 strains, highlighting the need for an active surveillance system to allow the rapid identification of new strains. PMID- 22309709 TI - Heavy metals and couple fecundity, the LIFE Study. AB - The effect of heavy metals at environmentally relevant concentrations on couple fecundity has received limited study despite ubiquitous exposure. In 2005-2009, couples (n=501) desiring pregnancy and discontinuing contraception were recruited and asked to complete interviews and to provide blood specimens for the quantification of cadmium (MUg L(-1)), lead (MUg dL(-1)) and mercury (MUg L(-1)) using inductively coupled plasma-mass spectrometry. Couples completed daily journals on lifestyle and intercourse along with menstruation and pregnancy testing for women. Couples were followed for 12 months or until pregnant. Fecundability odds ratios (FORs) and 95% confidence intervals (CIs) were estimated adjusting for age, body mass index, cotinine, and serum lipids in relation to female then male exposures. FORs <1 denote a longer time to pregnancy. In adjusted models, reduced FORs were observed for both female cadmium (0.78; 95% CI 0.63-0.97) and male lead (0.85; 95% CI 0.73-0.98) concentrations. When jointly modeling couples' exposures, only male lead concentration significantly reduced the FOR (0.82; 95% CI 0.68, 0.97), though the FOR remained <1 for female cadmium (0.80; 95% CI 0.64, 1.00). This prospective couple based cohort with longitudinal capture of time to pregnancy is suggestive of cadmium and lead's reproductive toxicity at environmentally relevant concentrations. PMID- 22309710 TI - Chromate reduction on humic acid derived from a peat soil--exploration of the activated sites on HAs for chromate removal. AB - Humic substances are a major component of soil organic matter that influence the behavior and fate of heavy metals such as Cr(VI), a toxic and carcinogenic element. In the study, a repetitive extraction technique was used to fractionate humic acids (HAs) from a peat soil into three fractions (denoted as F1, F2, and F3), and the relative importance of O-containing aromatic and aliphatic domains in humic substances for scavenging Cr(VI) was addressed at pH 1. Spectroscopic analyses indicated that the concentrations of aromatic C and O-containing functional groups decreased with a progressive extraction as follows: F1>F2>F3. Cr(VI) removal by HA proceeded slowly, but it was enhanced when light was applied due to the production of efficient reductants, such as superoxide radical and H(2)O(2), for Cr(VI). Higher aromatic- and O-containing F1 fraction exhibited a greater efficiency for Cr(VI) reduction (with a removal rate of ca. 2.89 mmol g( 1) HA under illumination for 3 h). (13)C NMR and FTIR spectra further demonstrated that the carboxyl groups were primarily responsible for Cr(VI) reduction. This study implied the mobility and fate of Cr(VI) would be greatly inhibited in the environments containing such organic groups. PMID- 22309711 TI - Use of whole-body and subcellular Cu residues of Lumbriculus variegatus to predict waterborne Cu toxicity to both L. variegatus and Chironomus riparius in fresh water. AB - We tested the use of whole-body and subcellular Cu residues (biologically-active (BAM) and inactive compartments (BIM)), of the oligochaete Lumbriculus variegatus to predict Cu toxicity in fresh water. The critical whole-body residue associated with 50% mortality (CBR(50)) was constant (38.2-55.6 MUg g(-1) fresh wt.) across water hardness (38-117 mg L(-1) as CaCO(3)) and exposure times during the chronic exposure. The critical subcellular residue (CSR(50)) in metal-rich granules (part of BIM) associated with 50% mortality was approximately 5 MUg g(-1) fresh wt., indicating that Cu bioavailability is correlated with toxicity:subcellular residue is a better predictor of Cu toxicity than whole-body residue. There was a strong correlation between the whole-body residue of L. variegatus (biomonitor) and survival of Chironomus riparius (relatively sensitive species) in a hard water Cu co-exposure. The CBR(50) in L. variegatus for predicting mortality of C. riparius was 29.1-45.7 MUg g(-1) fresh wt., which was consistent within the experimental period; therefore use of Cu residue in an accumulator species to predict bioavailability of Cu to a sensitive species is a promising approach. PMID- 22309712 TI - Immobilization of thermoalkalophilic recombinant esterase enzyme by entrapment in silicate coated Ca-alginate beads and its hydrolytic properties. AB - Thermoalkalophilic esterase enzyme from Balcova (Agamemnon) geothermal site were aimed to be immobilized effectively via a simple and cost-effective protocol in silicate coated Calcium alginate (Ca-alginate) beads by entrapment. The optimal immobilization conditions of enzyme in Ca-alginate beads were investigated and obtained with 2% alginate using 0.5mg/ml enzyme and 0.7 M CaCl(2) solution. In order to prevent enzyme from leaking out of the gel beads, Ca-alginate beads were then coated with silicate. Enzyme loading efficiency and immobilization yield for silicate coated beads was determined as 98.1% and 71.27%, respectively and compared with non-coated ones which were 68.5% and 45.80%, respectively. Surface morphologies, structure and elemental analysis of both silicate coated and non coated alginate beads were also compared using Fourier Transform Infrared Spectroscopy (FT-IR) and Scanning Electron Microscope (SEM) equipped with Energy dispersive X-ray spectroscopy (EDX). Moreover, silicate coated alginate beads enhanced reusability of esterase in continuous processes compared to non-coated beads. The hydrolytic properties of free and immobilized enzyme in terms of storage and thermal stability as well as the effects of the temperature and pH were determined. It was observed that operational, thermal and storage stabilities of the esterase were increased with immobilization. PMID- 22309713 TI - The M5-PS-35: a five-factor personality questionnaire for preschool children. AB - The Five-factor theory of personality (FFT) has pervaded personality research in recent years. Although many reliable and valid measurement instruments exist for use with adults, adolescents, and even elementary-age children, there is a lack of available 5-factor measurement tools for use with preschool children. This article expands on previous work developing the M5-PS, a rating form for preschool children designed to be completed by classroom teachers or caregivers. A total of 621 children were rated by their teachers on the 90-item working form of the M5-PS. Through a combination of empirical and rational scale refinement methods, the number of items has been reduced to 35, yielding a revised instrument, the M5-PS-35, with substantially improved construct validity and scale internal consistency. Potential changes in external validity were evaluated by comparative reanalysis of an existing data set. PMID- 22309714 TI - Prevalence of tet gene and complete genome sequencing of tet gene-encoded plasmid (pAHH01) isolated from Aeromonas species in South Korea. AB - AIMS: To investigate the tetracycline resistance related to tet genes in Aeromonas isolates collected from water and diseased fish in South Korea. METHODS AND RESULTS: A total of 34 Aeromonas strains were examined for their susceptibility to tetracycline using the minimum inhibitory concentration (MIC) assay, and the genetic determinants (tetA to E) were analysed. Among these strains, the tetA and tetE genes were predominant (tetA was found in six strains, and tetE was found in nine strains), and 15 strains were tetracycline-resistant by the MIC assay. Additionally, the 8979-bp plasmid that contains the tetE gene was fully sequenced. CONCLUSIONS: These data may be important with regard to the spread and persistence of tetracycline resistance genes in the bacterial populations that are present in aquaculture systems. SIGNIFICANCE AND IMPACT OF THE STUDY: Interestingly, no isolate has previously been shown to harbour three tet genes that are mediated by efflux systems, but the tetA, tetD and tetE genes were all isolated from one strain, which had the highest MIC value for tetracycline among the strains analysed in this study. We also investigated the full-length plasmid that encoded the tetE gene from a tetracycline-resistant strain. PMID- 22309715 TI - Stability and change in screen-based sedentary behaviours and associated factors among Norwegian children in the transition between childhood and adolescence. AB - BACKGROUND: In order to inform interventions to prevent sedentariness, more longitudinal studies are needed focusing on stability and change over time in multiple sedentary behaviours. This paper investigates patterns of stability and change in TV/DVD use, computer/electronic game use and total screen time (TST) and factors associated with these patterns among Norwegian children in the transition between childhood and adolescence. METHODS: The baseline of this longitudinal study took place in September 2007 and included 975 students from 25 control schools of an intervention study, the HEalth In Adolescents (HEIA) study. The first follow-up took place in May 2008 and the second follow-up in May 2009, with 885 students participating at all time points (average age at baseline = 11.2, standard deviation +/- 0.3). Time used for/spent on TV/DVD and computer/electronic games was self-reported, and a TST variable (hours/week) was computed. Tracking analyses based on absolute and rank measures, as well as regression analyses to assess factors associated with change in TST and with tracking high TST were conducted. RESULTS: Time spent on all sedentary behaviours investigated increased in both genders. Findings based on absolute and rank measures revealed a fair to moderate level of tracking over the 2 year period. High parental education was inversely related to an increase in TST among females. In males, self-efficacy related to barriers to physical activity and living with married or cohabitating parents were inversely related to an increase in TST. Factors associated with tracking high vs. low TST in the multinomial regression analyses were low self-efficacy and being of an ethnic minority background among females, and low self-efficacy, being overweight/obese and not living with married or cohabitating parents among males. CONCLUSIONS: Use of TV/DVD and computer/electronic games increased with age and tracked over time in this group of 11-13 year old Norwegian children. Interventions targeting these sedentary behaviours should thus be introduced early. The identified modifiable and non-modifiable factors associated with change in TST and tracking of high TST should be taken into consideration when planning such interventions. PMID- 22309716 TI - Asthma management and control in the United States: results of the 2009 Asthma Insight and Management survey. AB - Past asthma surveys have shown suboptimal management and control of asthma in the United States. No major survey of asthma management has been conducted since the Third Expert Panel Report for the National Asthma Education and Prevention Program (NAEPP) guidelines on diagnosis and treatment of asthma (August 2007). This study was designed to report asthma management and control results from the Asthma Insight and Management survey of U.S. patients and physicians. A telephone based survey was conducted during 2009 in 2500 patients with asthma, aged >=12 years, and 309 physicians (104 allergists, 54 pulmonologists, 101 family practitioners, and 50 internists). Patients' asthma control perceptions (71% "completely controlled" or "well controlled") were inconsistent with their NAEPP control level as determined by self-reported symptoms (29% well controlled). Patients and physicians had low expectations for effective asthma management; patients considered asthma well managed if rescue medication was used three times per week (46%), urgent care visits occurred twice per year (67%), or emergency department visits occurred once per year (60%). Asthma-related syncope, seizure, intensive care unit admission, and intubation were associated with uncontrolled asthma based on NAEPP guidelines. Respiratory specialists (allergists/pulmonologists) implemented asthma management recommendations more than other physicians surveyed. However, only 22% of patients visited a specialist for usual asthma care and 48% had never visited a specialist. Despite detailed NAEPP guidance, asthma management and control in U.S. patients is unsatisfactory. Improved asthma control assessment (impairment and risk) and implementation of NAEPP management recommendations are needed to improve asthma control and outcomes. PMID- 22309717 TI - Emotion words shape emotion percepts. AB - People believe they see emotion written on the faces of other people. In an instant, simple facial actions are transformed into information about another's emotional state. The present research examined whether a perceiver unknowingly contributes to emotion perception with emotion word knowledge. We present 2 studies that together support a role for emotion concepts in the formation of visual percepts of emotion. As predicted, we found that perceptual priming of emotional faces (e.g., a scowling face) was disrupted when the accessibility of a relevant emotion word (e.g., anger) was temporarily reduced, demonstrating that the exact same face was encoded differently when a word was accessible versus when it was not. The implications of these findings for a linguistically relative view of emotion perception are discussed. PMID- 22309718 TI - Memory for emotionally arousing events over time in Autism Spectrum Disorder. AB - Emotionally arousing events are typically better remembered and more resistant to forgetting than neutral events. Findings from word list paradigms suggest that this may not hold for individuals with Autism Spectrum Disorder (ASD), who also tend to be less accurate as eyewitnesses under some circumstances. To test whether attenuated effects of arousal on memory may be responsible for poorer eyewitness testimonies in ASD, we asked adults with and without the disorder to view either arousing or neutral versions of a narrated slide sequence (Experiment 1) or video clip (Experiment 2) before assessing their memory for the material. Both groups exhibited increases in psychophysiological arousal during the arousing compared with the neutral version of the narratives, and both groups also demonstrated a memory advantage for the arousing events. Contrary to predictions, these observations indicate that stimulus induced arousal modulates memory for naturalistic events relatively typically in ASD. PMID- 22309719 TI - Mindfulness and mind-wandering: finding convergence through opposing constructs. AB - Research into both mindfulness and mind-wandering has grown rapidly, yet clarification of the relationship between these two seemingly opposing constructs is still absent. A first study addresses the relationship between a dispositional measure of mindfulness (Mindful Attention and Awareness Scale, MAAS) and converging measures of both self-reported and indirect markers of mind-wandering. Negative correlations between dispositional mindfulness and 4 measures of mind wandering confirm the opposing relationship between the 2 constructs and further validate the use of the MAAS as a dispositional measure of mindfulness. A second study demonstrated that 8 minutes of mindful breathing reduces behavioral indicators of mind-wandering during a Sustained Attention to Response Task compared with both passive relaxation and reading. Together these studies clarify the opposition between the constructs of mindfulness and mind-wandering and so should lead to greater convergence between what have been predominately separate, yet mutually relevant, lines of research. PMID- 22309720 TI - Sleep deprivation and stressors: evidence for elevated negative affect in response to mild stressors when sleep deprived. AB - Stress often co-occurs with inadequate sleep duration, and both are believed to impact mood and emotion. It is not yet known whether inadequate sleep simply increases the intensity of subsequent stress responses or interacts with stressors in more complicated ways. To address this issue, we investigated the effects of one night of total sleep deprivation on subjective stress and mood in response to low-stress and high-stress cognitive testing conditions in healthy adult volunteers in two separate experiments (total N = 53). Sleep was manipulated in a controlled, laboratory setting and stressor intensity was manipulated by changing difficulty of cognitive tasks, time pressure, and feedback about performance. Sleep-deprived participants reported greater subjective stress, anxiety, and anger than rested controls following exposure to the low-stressor condition, but not in response to the high-stressor condition, which elevated negative mood and stress about equally for both sleep conditions. These results suggest that sleep deprivation lowers the psychological threshold for the perception of stress from cognitive demands but does not selectively increase the magnitude of negative affect in response to high-stress performance demands. PMID- 22309721 TI - When getting angry is smart: emotional preferences and emotional intelligence. AB - People who prefer to feel useful emotions, even when they are unpleasant to experience, must understand emotions and seek to regulate them in strategic ways. Such people, therefore, may be more emotionally intelligent compared with people who prefer to feel emotions that may not be useful for the context at hand, even if those emotions are pleasant to experience. We tested this hypothesis by measuring emotional intelligence and preferences to feel pleasant and unpleasant emotions in contexts in which they are likely to be useful or not. We found significant positive associations between emotional intelligence and preferences for useful emotions, even when controlling for trait emotional experiences and cognitive intelligence. People who prefer to feel anger when confronting others tend to be higher in emotional intelligence, whereas people who prefer to feel happiness in such contexts tend to be lower in emotional intelligence. Such findings are consistent with the idea that wanting to feel bad may be good at times, and vice versa. PMID- 22309722 TI - Stirring images: fear, not happiness or arousal, makes art more sublime. AB - Which emotions underlie our positive experiences of art? Although recent evidence from neuroscience suggests that emotions play a critical role in art perception, no research to date has explored the extent to which specific emotional states affect aesthetic experiences or whether general physiological arousal is sufficient. Participants were assigned to one of five conditions-sitting normally, engaging in 15 or 30 jumping jacks, or viewing a happy or scary video prior to rating abstract works of art. Only the fear condition resulted in significantly more positive judgments about the art. These striking findings provide the first evidence that fear uniquely inspires positively valenced aesthetic judgments. The results are discussed in the context of embodied cognition. PMID- 22309723 TI - Toward a phenomenology of feelings. AB - Our understanding of emotion cannot be complete without an understanding of feelings, the experiential aspect of emotion. Despite their importance, little effort has been devoted to the careful apprehension of feelings. Based on our apprehension of many randomly selected moments of pristine inner experience, we present a preliminary phenomenology of feelings. We begin by observing that often feelings occur as directly experienced phenomena of awareness; however, often no feelings are present in experience, or if they are present, they are too faint to be observed by a process intended to observe them. Feelings range from vague to distinct and sometimes do, but other times do not, include bodily sensations. When bodily sensations are present, there is a wide range of clarity and location of these sensations. Sometimes people experience multiple distinct feelings and sometimes people experience one feeling that is a mix or blend of different feelings. We also discuss what feelings are not, including instances when feelings do not appear to be present, despite evidence suggesting the presence of underlying emotional processes (e.g., behavioral evidence of emotion). These instances of emotion but not feeling lead us to speculate that experiencing feelings is a skill developed over time through an interaction of interpersonal and intrapersonal events. PMID- 22309724 TI - Should people pursue feelings that feel good or feelings that do good? Emotional preferences and well-being. AB - Is it adaptive to seek pleasant emotions and avoid unpleasant emotions all the time or seek pleasant and unpleasant emotions at the right time? Participants reported on their preferences for anger and happiness in general and in contexts in which they might be useful or not (i.e., confrontations and collaborations, respectively). People who generally wanted to feel more happiness and less anger experienced greater well-being. However, when emotional preferences were examined in context, people who wanted to feel more anger or more happiness when they were useful, and people who wanted to feel less of those emotions when they were not useful, experienced greater well-being. Such patterns could not be explained by differences in the perceived usefulness of emotions, intelligence, perceived regulatory skills, emotional acceptance, social desirability, or general emotional preferences. These findings demonstrate that people who want to feel unpleasant emotions when they are useful may be happier overall. PMID- 22309725 TI - Attentional bias to negative information and 5-HTTLPR genotype interactively predict students' emotional reactivity to first university semester. AB - People strongly differ in their emotional reactions to potentially stressing and challenging environmental circumstances. Two classes of individual differences have independently been reported to contribute to such emotional vulnerability: an attentional bias to negative information and a variation in the serotonin transporter gene (5-HTTLPR). The present study was conducted to investigate the possibility that these cognitive and genetic markers interact in their prospective prediction of emotional reactivity to an extended and mild potential stressor. Changes in dysphoria and anxiety across their first university semester were measured in 120 students. Results indicate that attentional bias toward negative information on Week 1 of the semester significantly predicted cross semester changes in both anxiety and dysphoria. For the latter, this predictive capacity depended on the 5-HTTLPR genotype. Specifically, only in homozygous carriers of the 5-HTTLPR short allele did attentional bias to negative information on Week 1 significantly predict cross-semester change in dysphoria. These results carry important theoretical and practical implications concerning the ability to identify individuals vulnerable to experiencing elevated emotional reactivity to potentially stressing life-events. PMID- 22309726 TI - Psychopathy and fear: specific impairments in judging behaviors that frighten others. AB - Psychopathy is a disorder associated with antisocial behavior and deficits in responding to emotional stimuli, particularly fear-related stimuli. This research demonstrates that these deficits extend to judgments about behaviors that cause fear in others. We assessed whether psychopathy is associated with the ability to identify the emotional consequences of social behaviors and with judgments about these behaviors' acceptability. We found that psychopathy, as indexed by the Psychopathic Personality Inventory, is associated with impairments in identifying behaviors that cause fear and in judging the moral acceptability of these behaviors. Ratings of emotional consequences and moral acceptability were also correlated, such that individuals who less accurately identified behaviors that cause fear also judged these behaviors to be more morally acceptable. Psychopathy scores mediated the relationship between these two variables. These findings suggest that understanding that frightening others is unacceptable relies on understanding this type of behavior's emotional consequences, and have significance for understanding the relationship between psychopathy, empathy, and antisocial behavior. PMID- 22309727 TI - Positive emotional context eliminates the framing effect in decision-making. AB - Dual-process theories have suggested that emotion plays a key role in the framing effect in decision-making. However, little is known about the potential impact of a specific positive or negative emotional context on this bias. We investigated this question with adult participants using an emotional priming paradigm. First, participants were presented with positive or negative affective pictures (i.e., pleasant vs. unpleasant photographs). Afterward, participants had to perform a financial decision-making task that was unrelated to the pictures previously presented. The results revealed that the presentation framed in terms of gain or loss no longer affected subjects' decision-making following specific exposure to emotionally pleasant pictures. Interestingly, a positive emotional context did not globally influence risk-taking behavior but specifically decreased the risk propensity in the loss frame. This finding confirmed that a positive emotional context can reduce loss aversion, and it strongly reinforced the dual-process view that the framing effect stems from an affective heuristic belonging to intuitive System 1. PMID- 22309728 TI - Not just another face in the crowd: detecting emotional schematic faces during continuous flash suppression. AB - To test whether threatening visual information receives prioritized processing, many studies have examined visual search for emotional schematic faces. Still, it has remained unclear whether negative or positive schematic faces are processed more efficiently. We used continuous flash suppression, a variant of binocular rivalry, to render single emotional schematic faces invisible and measured whether negative or positive faces have an advantage in accessing awareness. Across three experiments, positive faces were detected more quickly than negative faces. A fourth experiment indicated that this positive face advantage was unrelated to the valence of the face stimuli but due to the relative orientation of the mouth curvature and the face contour. These findings demonstrate the impact of configural stimulus properties on perceptual suppression during binocular rivalry and point to a perceptual confound present in emotional schematic faces that might account for some ambiguous results obtained with schematic face stimuli in previous studies. PMID- 22309729 TI - Affect intensity in voice recognized by tree shrews (Tupaia belangeri). AB - Shared acoustic cues in speech, music, and nonverbal emotional expressions were postulated to code for emotion quality and intensity favoring the hypothesis of a prehuman origin of affective prosody in human emotional communication. To explore this hypothesis, we examined in playback experiments using a habituation dishabituation paradigm whether a solitary foraging, highly vocal mammal, the tree shrew, is able to discriminate two behaviorally defined states of affect intensity (low vs. high) from the voice of conspecifics. Playback experiments with communication calls of two different types (chatter call and scream call) given in the state of low affect intensity revealed that habituated tree shrews dishabituated to one call type (the chatter call) and showed a tendency to do so for the other one (the scream call), both given in the state of high affect intensity. Findings suggest that listeners perceive the acoustic variation linked to defined states of affect intensity as different within the same call type. Our findings in tree shrews provide first evidence that acoustically conveyed affect intensity is biologically relevant without any other sensory cue, even for solitary foragers. Thus, the perception of affect intensity in voice conveyed in stressful contexts represents a shared trait of mammals, independent of the complexity of social systems. Findings support the hypothesis that affective prosody in human emotional communication has deep-reaching phylogenetic roots, deriving from precursors already present and relevant in the vocal communication system of early mammals. PMID- 22309730 TI - Competing for attentional priority: temporary goals versus threats. AB - Numerous studies have shown that attention is biased toward threatening events. More recent evidence has also found attentional biases for stimuli that are relevant to the current and temporary goals of an individual. We examined whether goal-relevant information still evokes an attentional bias when this information competes with threatening events. In three experiments, participants performed a dot probe task combined with a separate task that induced a temporary goal. The results of Experiment 1 showed that attention was oriented to goal-relevant pictures in the dot probe task when these pictures were simultaneously presented with neutral or threatening pictures. Whether goal-relevant pictures themselves were threatening or neutral did not influence the results. Experiment 2 replicated these findings in a sample of highly trait-anxious participants. Experiment 3 showed that attention was automatically deployed to stimuli relevant to a temporary goal even in the presence of stimuli that signal imminent and genuine threat (i.e., a colored patch signaling the presentation of an aversive noise). These findings further corroborate the conclusion that an individual's current and temporary goals guide early attentional processes. PMID- 22309731 TI - Memory and attention for social threat: anxious hypercoding-avoidance and submissive gaze aversion. AB - Rivalry for dominance is a recurrent challenge in human social interaction. During these social dominance interactions, some people rapidly break eye contact, whereas others merely try to avoid such eye-to-eye confrontations. The first is an example of submissive gaze aversion, whereas the second reflects anxious gaze avoidance. We tested these distinct forms of gaze behavior within a social-memory setting and show that anxious individuals vigilantly attend to, superiorly remember, and subsequently avoid social threats (i.e., angry faces). Furthermore, submissive individuals, as indexed by high trait anxiety and low trait anger, exhibit rapid gaze aversion from facial anger. Mechanisms of hypervigilance-avoidance thus seem to underlie natural gaze behavior and enhanced memory for threat in anxiety. Accordingly, we propose the term hypercoding avoidance, which describes how anxious individuals habitually scan their immediate social environment for threat, remember its location, and subsequently avoid it. Moreover, this is the first experimental evidence showing that submissive gaze aversion is distinct from anxious gaze avoidance. PMID- 22309732 TI - Happy as a lark: morning-type younger and older adults are higher in positive affect. AB - A literature on young adults reports that morning-type individuals, or "larks," report higher levels of positive affect compared with evening-type individuals, or "owls" (Clark, Watson, & Leeka, 1989; Hasler et al., 2010). Morning types are relatively rare among young adults but frequent among older adults (May & Hasher, 1998; Mecacci et al., 1986), and here we report on the association between chronotype and affect in a large sample of healthy younger and older adults. Overall, older adults reported higher levels of positive affect than younger adults, with both younger and older morning types reporting higher levels of positive affect and subjective health than age mates who scored lower on morningness. Morningness partially mediated the association between age and positive affect, suggesting that greater morningness tendencies among older adults may contribute to their improved well-being relative to younger adults. PMID- 22309733 TI - Opening editorial. PMID- 22309734 TI - Human anterior and posterior hippocampus respond distinctly to state and trait anxiety. AB - We examined whether anterior and posterior hippocampal subregions in humans show distinct relationships to state and trait anxiety. In rodents, the ventral (but not dorsal) hippocampus is critically involved in contextual anxiety, whereas dorsal hippocampus is affected by chronic stress and genetically bred trait anxiety. These studies suggest that state forms of anxiety may be more associated with anterior (ventral in rodents) hippocampus, whereas trait forms of anxiety maybe more associated with posterior (dorsal in rodents) hippocampus. Participants were placed under alternating blocks of threat of shock and safety conditions while performing a secondary task, and state and trait anxiety measures were obtained. Using subject-specific anatomically defined masks, we found that state anxiety was related to activity in anterior but not posterior hippocampus, whereas trait anxiety showed the opposite pattern. Additionally, a psychophysiological connectivity analysis showed that activity in anterior hippocampus was more strongly related to activity in ventromedial prefrontal cortex under threat than under safety conditions, significantly more so than activity in posterior hippocampus was. Hence, anterior hippocampus shows a distinct moment-to-moment connectivity profile with other neural regions during threat relative to posterior hippocampus. The findings provide several lines of evidence for functional differentiation of anterior and posterior hippocampal involvement across state and trait components of anxiety in humans. PMID- 22309735 TI - Trypanosoma cruzi discrete typing units in Chagas disease patients from endemic and non-endemic regions of Argentina. AB - Genetic diversity of Trypanosoma cruzi may play a role in pathogenesis of Chagas disease forms. Natural populations are classified into 6 Discrete Typing Units (DTUs) Tc I-VI with taxonomical status. This study aimed to identify T. cruzi DTUs in bloodstream and tissue samples of Argentinean patients with Chagas disease. PCR-based strategies allowed DTU identification in 256 clinical samples from 239 Argentinean patients. Tc V prevailed in blood from both asymptomatic and symptomatic cases and Tc I was more frequent in bloodstream, cardiac tissues and chagoma samples from immunosuppressed patients. Tc II and VI were identified in a minority of cases, while Tc III and Tc IV were not detected in the studied population. Interestingly, Tc I and Tc II/VI sequences were amplified from the same skin biopsy slice from a kidney transplant patient suffering Chagas disease reactivation. Further data also revealed the occurrence of mixed DTU populations in the human chronic infection. In conclusion, our findings provide evidence of the complexity of the dynamics of T. cruzi diversity in the natural history of human Chagas disease and allege the pathogenic role of DTUs I, II, V and VI in the studied population. PMID- 22309736 TI - Wnt proteins regulate acetylcholine receptor clustering in muscle cells. AB - BACKGROUND: The neuromuscular junction (NMJ) is a cholinergic synapse that rapidly conveys signals from motoneurons to muscle cells and exhibits a high degree of subcellular specialization characteristic of chemical synapses. NMJ formation requires agrin and its coreceptors LRP4 and MuSK. Increasing evidence indicates that Wnt signaling regulates NMJ formation in Drosophila, C. elegans and zebrafish. RESULTS: In the study we systematically studied the effect of all 19 different Wnts in mammals on acetylcholine receptor (AChR) cluster formation. We identified five Wnts (Wnt9a, Wnt9b, Wnt10b, Wnt11, and Wnt16) that are able to stimulate AChR clustering, of which Wnt9a and Wnt11 are expressed abundantly in developing muscles. Using Wnt9a and Wnt11 as example, we demonstrated that Wnt induction of AChR clusters was dose-dependent and non-additive to that of agrin, suggesting that Wnts may act via similar pathways to induce AChR clusters. We provide evidence that Wnt9a and Wnt11 bind directly to the extracellular domain of MuSK, to induce MuSK dimerization and subsequent tyrosine phosphorylation of the kinase. In addition, Wnt-induced AChR clustering requires LRP4. CONCLUSIONS: These results identify Wnts as new players in AChR cluster formation, which act in a manner that requires both MuSK and LRP4, revealing a novel function of LRP4. PMID- 22309737 TI - High-pressure intrapleural chemotherapy: feasibility in the pig model. AB - BACKGROUND: The usual treatments for pleural malignancies are mostly palliative. In contrast, peritoneal malignancies are often treated with a curative intent by cytoreductive surgery and intraperitoneal chemotherapy. As pressure has been shown to increase antitumor efficacy, we applied the concept of high-pressure intracavitary chemotherapy to the pleural space in a swine model. METHODS: Cisplatin and gemcitabine were selected because of their antineoplasic efficacy in vitro in a wide spectrum of cancer cell lines. The pleural cavity of 21 pigs was filled with saline solution; haemodynamic and respiratory parameters were monitored. The pressure was increased to 15-25 cm H2O. This treatment was associated with pneumonectomy in 6 pigs. Five pigs were treated with chemotherapy under pressure. RESULTS: The combination of gemcitabine (100 mg/l) and cisplatin (30 mg/l) was highly cytotoxic in vitro. The maximum tolerated pressure was 20 cm H20, due to haemodynamic failure. Pneumonectomy was not tolerated, either before or after pleural infusion. Five pigs survived intrapleural chemotherapy associating gemcitabine and cisplatin with 20 cm H2O pressure for 60 min. CONCLUSIONS: High-pressure intrapleural chemotherapy is feasible in pigs. Further experiments will establish the pharmacokinetics and determine whether the benefit already shown in the peritoneum is also obtained in the pleura. PMID- 22309738 TI - After-school physical activity and eating behaviors of middle school students in relation to adult supervision. AB - OBJECTIVE: Examine after-school activity patterns, eating behaviors, and social environment of overweight and normal weight middle school students. DESIGN: Eating and physical activity behaviors of 141 students, ages 10-14, were monitored. Students completed a diary documenting type of activity, location, adult supervision, accompanying participants, and eating habits from 3:00 pm 12:00 am. SETTING: Three middle schools, grades 6-8. MAIN OUTCOME MEASURES: Body mass index, estimated energy expenditure, eating behavior, active time, sedentary time, supervised time. ANALYSIS: t tests, ANOVA, chi-square, correlation coefficients. Significance set at P < .05. RESULTS: Children spent 76% of time sedentary, and 85% of sedentary time was under adult supervision (r = 0.76). Active time related to time with friends (r = 0.64) and family (r = 0.46). Children spent 40% of eating time consuming unhealthful food, and adults supervised 86% of children's eating. Overweight and normal weight children were similarly active (335 +/- 156 vs 373 +/- 194 counts per minute). Overweight girls spent more eating time (77%) eating healthfully than overweight boys (57%). CONCLUSIONS AND IMPLICATIONS: Children should be given access to healthful food and encouraged to eat healthfully when alone and with friends. Adults should be more physically engaged with children. Children should be encouraged to eat under adult supervision and with their families. PMID- 22309739 TI - Root perforation associated with the use of a miniscrew implant used for orthodontic anchorage: a case report. AB - AIM: To highlight one of the possible complications associated with the inter radicular placement of orthodontic miniscrews. SUMMARY: This case report describes the endodontic treatment and surgical repair of an iatrogenic root perforation involving a maxillary first molar tooth following the placement of an orthodontic miniscrew placed for anchorage purposes in the treatment of an adult patient. The orthodontic treatment plan was completed. The long-term follow-up shows a successful treatment outcome. KEY LEARNING POINTS: Inter-radicular placement of orthodontic miniscrews is a valuable source of anchorage in the treatment of orthodontic patients. Root perforation is a possible complication from inter-radicular placement of orthodontic miniscrews. Root perforation can be successfully treated, but may involve apical surgery. PMID- 22309740 TI - Testing the effectiveness of two improved cookstove interventions in the Santiago de Chuco Province of Peru. AB - 90% of people residing in rural areas of less-developed countries rely on coal and biomass fuels for heating and cooking, leading to high exposures to the products of incomplete combustion. Three Andean communities within the Santiago de Chuco province of Peru received two different models of improved cookstoves. The impact of these stoves in reducing personal exposures and kitchen concentrations of fine particulate matter (PM(2.5)) and carbon monoxide (CO) was evaluated separately in 64 homes (32 with each stove model) using air monitoring equipment. In the community receiving stove 1, baseline aggregate 48-h personal exposure (n=27) and kitchen concentrations (n=26) of PM(2.5) were 116.4 and 207.3MUg/m(3), respectively, and 48-h personal (n=25) and kitchen (n=25) CO levels were 1.2 and 3.6ppm. After introducing the new stove to this community, those exposures reduced to 68.4 and 84.7MUg/m(3), and 0.4 and 0.8ppm, representing reductions of 41.3%, 59.2%, 69.6% and 77.7% respectively. In the two communities receiving stove 2, corresponding levels were 126.3MUg/m(3) (n=18), 173.4MUg/m(3) (n=19), 0.9ppm (n=19), and 2.6ppm (n=17) before the installation of the stoves, and they reduced to 58.3, 51.1MUg/m(3) and 0.6, 1.0ppm. Overall, homes receiving stove 2 saw reductions of 53.8, 70.5, 25.8 and 63.6%. All values are statistically significant (p<0.05) with the exception of personal CO reductions in the stove 2 group. Both stoves markedly reduce both kitchen and personal levels of wood smoke exposure, which we believe has the potential to improve health and quality of life. PMID- 22309741 TI - Salidroside stimulates the accumulation of HIF-1alpha protein resulted in the induction of EPO expression: a signaling via blocking the degradation pathway in kidney and liver cells. AB - Rhodiolae Crenulatae Radix et Rhizoma (Rhodiola), the root and rhizome of Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba, has been used as a traditional Chinese medicine (TCM) to increase the body resistance to mountain sickness in preventing hypoxia; however, the functional ingredient responsible for this adaptogenic effect has not been revealed. Here, we have identified salidroside, a glycoside predominantly found in Rhodiola, is the chemical in providing such anti hypoxia effect. Cultured human embryonic kidney fibroblast (HEK293T) and human hepatocellular carcinoma (HepG2) were used to reveal the mechanism of this hematopoietic function mediated by salidroside. The application of salidroside in cultures induced the expression of erythropoietin (EPO) mRNA from its transcription regulatory element hypoxia response element (HRE), located on EPO gene. The application of salidroside stimulated the accumulation of hypoxia inducible factor-1alpha (HIF-1alpha) protein, but not HIF-2alpha protein: the salidroside-induced HIF-1alpha protein was via the reduction of HIF-1alpha degradation but not the mRNA induction. The increased HIF-1alpha could account for the activation of EPO gene. These results supported the notion that hematopoietic function of Rhodiola was triggered, at least partially, by salidroside. PMID- 22309742 TI - Epidemiology, disease spectrum and economic burden of non-typhoidal Salmonella infections in Taiwan, 2006-2008. AB - The purpose of this study was to understand the seasonal, geographical and clinical characteristics of Taiwanese patients hospitalized for non-typhoidal Salmonella (NTS) infections and their economic burden. Hospital data obtained from the Taiwan National Health Insurance (NHI) database between 2006 and 2008 were analysed. Infants had the highest annual incidence of 525 cases/100 000 person-years. Elderly patients aged >70 years had the highest in-hospital mortality rate (2.6%). Most (82.6%) gastroenteritis occurred in children aged <10 years. Septicaemia, pneumonia, arthritis and osteomyelitis occurred mainly in patients aged >50 years. A median medical cost for NTS-associated hospitalizations was higher for patients with septicaemia than for those with gastroenteritis. Seasonal variation of NTS-associated hospitalizations was correlated with temperature in different areas of Taiwan. In summary, infants had a high incidence of NTS-associated hospitalizations. However, the elderly had a higher in-hospital mortality rate and more invasive NTS infections than children. PMID- 22309743 TI - Following a natural experiment of guideline adaptation and early implementation: a mixed-methods study of facilitation. AB - BACKGROUND: Facilitation is emerging as an important strategy in the uptake of evidence. However, it is not entirely clear from a practical perspective how facilitation occurs to help move research evidence into nursing practice. The Canadian Partnership Against Cancer, also known as the 'Partnership,' is a Pan Canadian initiative supporting knowledge translation activity for improved care through guideline use. In this case-series study, five self-identified groups volunteered to use a systematic methodology to adapt existing clinical practice guidelines for Canadian use. With 'Partnership' support, local and external facilitators provided assistance for groups to begin the process by adapting the guidelines and planning for implementation. METHODS: To gain a more comprehensive understanding of the nature of facilitation, we conducted a mixed-methods study. Specifically, we examined the role and skills of individuals actively engaged in facilitation as well as the actual facilitation activities occurring within the 'Partnership.' The study was driven by and builds upon a focused literature review published in 2010 that examined facilitation as a role and process in achieving evidence-based practice in nursing. An audit tool outlining 46 discrete facilitation activities based on results of this review was used to examine the facilitation noted in the documents (emails, meeting minutes, field notes) of three nursing-related cases participating in the 'Partnership' case-series study. To further examine the concept, six facilitators were interviewed about their practical experiences. The case-audit data were analyzed through a simple content analysis and triangulated with participant responses from the focus group interview to understand what occurred as these cases undertook guideline adaptation. RESULTS: The analysis of the three cases revealed that almost all of the 46 discrete, practical facilitation activities from the literature were evidenced. Additionally, case documents exposed five other facilitation-related activities, and a combination of external and local facilitation was apparent. Individuals who were involved in the case or group adapting the guideline(s) also performed facilitation activities, both formally and informally, in conjunction with or in addition to appointed external and local facilitators. CONCLUSIONS: Facilitation of evidence-based practice is a multifaceted process and a team effort. Communication and relationship-building are key components. The practical aspects of facilitation explicated in this study validate what has been previously noted in the literature and expand what is known about facilitation process and activity. PMID- 22309744 TI - [Guidelines for specialized nutritional and metabolic support in the critically ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC SENPE): introduction and methodology]. AB - The Recommendations for Specialized Nutritional Support in Critically-Ill patients were drafted by the Metabolism and Nutrition Working Group of the Spanish Society of Intensive Care Medicine and Coronary Units (SEMICYUC) in 2005. Given the time elapsed since then, these recommendations have been reviewed and updated as a Consensus Document in collaboration with the Spanish Society of Parenteral and Enteral Nutrition (SENPE). The primary aim of these Recommendations was to evaluate the best available scientific evidence for the indications of specialized nutritional and metabolic support in critically-ill patients. The Recommendations have been formulated by an expert panel with broad experience in nutritional and metabolic support in critically-ill patients and were drafted between October 2009 and March 2011. The studies analyzed encompassed metaanalyses, randomized clinical trials, observational studies, systematic reviews and updates relating to critically-ill adults in MEDLINE from 1966 to 2010, EMBASE reviews from 1991 to 2010 and the Cochrane Database of Systematic Reviews up to 2010. The methodological criteria selected were those established in the Scottish Intercollegiate Guidelines Network and the Agency for Health Care policy and Research, as well as those of the Jadad Quality Scale. Adjustment for the level of evidence and grade of recommendation was performed following the proposal of the GRADE group (Grading of Recommendations Assessment, Development and Evaluation Working Group). Sixteen pathological scenarios were selected and each of them was developed by groups of three experts. A feedback system was established with the five members of the Editorial Committee and with the entire Working Group. All discrepancies were discussed and consensus was reached over several meetings, with special emphasis placed on reviewing the levels of evidence and grades of recommendation. The Editorial Committee made the final adjustments before the document was approved by all the members of the Working Group. Finally, the document was submitted to the Scientific Committees of the two Societies participating in the Consensus for final approval. The present Recommendations aim to serve as a guide for clinicians involved in the management and treatment of critically-ill patients and for any specialists interested in the nutritional treatment of hospitalized patients. PMID- 22309745 TI - [Guidelines for specialized nutritional and metabolic support in the critically ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC SENPE): indications, timing and routes of nutrient delivery]. AB - This article discusses basic features of nutritional support in critically-ill patients: general indications, the route of administration and the optimal timing for the introduction of feeding. Although these features form the bedrock of nutritional support, most of the questions related to these issues are lacking answers based on the highest grade of evidence. Moreover, prospective randomized trials that might elucidate some o f these questions would probably be incompatible with good clinical practice. Nevertheless, nutritional support in critically-ill patients unable to voluntarily meet their own nutritional requirements is currently an unquestionable part of their treatment and care and is essential to the successful management of their illness. PMID- 22309746 TI - [Guidelines for specialized nutritional and metabolic support in the critically ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC SENPE): nutritional assessment]. AB - Current parameters to assess nutritional status in critically-ill patients are useful to evaluate nutritional status prior to admission to the intensive care unit. However, these parameters are of little utility once the patient's nutritional status has been altered by the acute process and its treatment. Changes in water distribution affect anthropometric variables and biochemical biomarkers, which in turn are affected by synthesis and degradation processes. Increased plasma levels of prealbumin and retinol -proteins with a short half life- can indicate adequate response to nutritional support, while reduced levels of these proteins indicate further metabolic stress. The parameters used in functional assessment, such as those employed to assess muscular or immune function, are often altered by drugs or the presence of infection or polyneuropathy. However, some parameters can be used to monitor metabolic response and refeeding or can aid prognostic evaluation. PMID- 22309747 TI - [Guidelines for specialized nutritional and metabolic support in the critically ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC SENPE): macro-and micronutrient requirements]. AB - Energy requirements are altered in critically-ill patients and are influenced by the clinical situation, treatment, and phase of the process. Therefore, the most appropriate method to calculate calorie intake is indirect calorimetry. In the absence of this technique, fixed calorie intake (between 25 and 35 kcal/kg/day) or predictive equations such as the Penn State formula can be used to obtain a more accurate evaluation of metabolic rate. Carbohydrate administration should be limited to a maximum of 4 g/kg/day and a minimum of 2g/kg/day. Plasma glycemia should be controlled to avoid hyperglycemia. Fat intake should be between 1 and 1.5 g/kg/day. The recommended protein intake is 1-1.5 g/kg/day but can vary according to the patient's clinical status. Particular attention should be paid to micronutrient intake. Consensus is lacking on micronutrient requirements. Some vitamins (A, B, C, E) are highly important in critically-ill patients, especially those undergoing continuous renal replacement techniques, patients with severe burns and alcoholics, although the specific requirements in each of these types of patient have not yet been established. Energy and protein intake in critically ill patients is complex, since both clinical factors and the stage of the process must be taken into account. The first step is to calculate each patient's energy requirements and then proceed to distribute calorie intake among its three components: proteins, carbohydrates and fat. Micronutrient requirements must also be considered. PMID- 22309748 TI - [Guidelines for specialized nutritional and metabolic support in the critically ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC SENPE): acute renal failure]. AB - Nutritional support in acute renal failure must take into account the patient's catabolism and the treatment of the renal failure. Hypermetabolic failure is common in these patients, requiring continuous renal replacement therapy or daily hemodialysis. In patients with normal catabolism (urea nitrogen below 10 g/day) and preserved diuresis, conservative treatment can be attempted. In these patients, relatively hypoproteic nutritional support is essential, using proteins with high biological value and limiting fluid and electrolyte intake according to the patient's individual requirements. Micronutrient intake should be adjusted, the only buffering agent used being bicarbonate. Limitations on fluid, electrolyte and nitrogen intake no longer apply when extrarenal clearance techniques are used but intake of these substances should be modified according to the type of clearance. Depending on their hemofiltration flow, continuous renal replacement systems require high daily nitrogen intake, which can sometimes reach 2.5 g protein/kg. The amount of volume replacement can induce energy overload and therefore the use of glucose-free replacement fluids and glucose free dialysis or a glucose concentration of 1 g/L, with bicarbonate as a buffer, is recommended. Monitoring of electrolyte levels (especially those of phosphorus, potassium and magnesium) and of micronutrients is essential and administration of these substances should be individually-tailored. PMID- 22309749 TI - [Guidelines for specialized nutritional and metabolic support in the critically ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC SENPE): liver failure and transplantation]. AB - Patients with liver failure have a high prevalence of malnutrition, which is related to metabolic abnormalities due to the liver disease, reduced nutrient intake and alterations in digestive function, among other factors. In general, in patients with liver failure, metabolic and nutritional support should aim to provide adequate nutrient intake and, at the same time, to contribute to patients' recovery through control or reversal of metabolic alterations. In critically-ill patients with liver failure, current knowledge indicates that the organ failure is not the main factor to be considered when choosing the nutritional regimen. As in other critically-ill patients, the enteral route should be used whenever possible. The composition of the nutritional formula should be adapted to the patient's metabolic stress. Despite the physiopathological basis classically described by some authors who consider amino acid imbalance to be a triggering factor and key element in maintaining encephalopathy, there are insufficient data to recommend "specific" solutions (branched-chain amino acid-enriched with low aromatic amino acids) as part of nutritional support in patients with acute liver failure. In patients undergoing liver transplantation, nutrient intake should be started early in the postoperative period through transpyloric access. Prevention of the hepatic alterations associated with nutritional support should also be considered in distinct clinical scenarios. PMID- 22309750 TI - [Guidelines for specialized nutritional and metabolic support in the critically ill-patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC SENPE): severe acute pancreatitis]. AB - Severe acute pancreatitis (SAP) causes local and systemic complications leading to high catabolic, hypermetabolic and hyperdynamic stress states with marked morbidity and mortality. In the last decade, nutritional support has become a key element in the treatment of SAP. Thus, specialized nutrition is indicated from admission, with enteral nutrition being preferred to parenteral nutrition. Enteral nutrition should be initiated early using infusion through the jejunum beyond the ligament of Treitz to minimize pancreatic stress. There are no specific studies that establish the type of diet to be used but experts recommend the use of polymeric diets. Parenteral nutrition, without a specific formula, is indicated in patients with SAP who are intolerant to enteral nutrition or when the clinical signs of pancreatitis are exacerbated or aggravated by enteral nutrition. Even so, a minimal level of enteral infusion should be maintained to preserve the trophic effect of the intestinal mucosa. In the last few years, several studies of the administration of immunomodulatory diets in patients with SAP have been carried out to demonstrate their effects on the course of the disease. However, there are few clear recommendations on the prognostic benefits of pharmaconutrient enriched diets in these patients. There is substantial scientific evidence suggesting that the only clear indication for pharmaconutrition in patients with SAP is parenteral glutamine administration, which is recommended by all clinical guidelines with distinct grades of evidence. PMID- 22309751 TI - [Guidelines for specialized nutritional and metabolic support in the critically ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC SENPE): respiratory failure]. AB - Severe acute respiratory failure requiring mechanical ventilation is one of the most frequent reasons for admission to the intensive care unit. Among the most frequent causes for admission are exacerbation of chronic obstructive pulmonary disease and acute respiratory failure with acute lung injury (ALI) or with criteria of acute respiratory distress syndrome (ARDS). These patients have a high risk of malnutrition due to the underlying disease, their altered catabolism and the use of mechanical ventilation. Consequently, nutritional evaluation and the use of specialized nutritional support are required. This support should alleviate the catabolic effects of the disease, avoid calorie overload and, in selected patients, to use omega-3 fatty acid- and antioxidant-enriched diets, which could improve outcome. PMID- 22309752 TI - [Guidelines for specialized nutritional and metabolic support in the critically ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC SENPE): gastrointestinal surgery]. AB - Gastrointestinal surgery and critical illness place tremendous stress on the body, resulting in a series of metabolic changes that may lead to severe malnutrition, which in turn can increase postsurgical complications and morbidity and mortality and prolong the hospital length of stay. In these patients, parenteral nutrition is the most widely used form of nutritional support, but administration of enteral nutrition early in the postoperative period is effective and well tolerated, reducing infectious complications, improving wound healing and reducing length of hospital stay. Calorie-protein requirements do not differ from those in other critically-ill patients and depend on the patient's underlying process and degree of metabolic stress. In patients intolerant to enteral nutrition, especially if the intolerance is due to increased gastric residual volume, prokinetic agents can be used to optimize calorie intake. When proximal sutures are used, tubes allowing early jejunal feeding should be used. Pharmaconutrition is indicated in these patients, who benefit from enteral administration of arginine, omega 3 and RNA, as well as parenteral glutamine supplementation. Parenteral nutrition should be started in patients with absolute contraindication for use of the gastrointestinal tract or as complementary nutrition if adequate energy intake is not achieved through the enteral route. PMID- 22309753 TI - [Guidelines for specialized nutritional and metabolic support in the critically ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC SENPE): hyperglycemia and diabetes mellitus]. AB - Hyperglycemia is one of the main metabolic disturbances in critically-ill patients and is associated with increased morbidity and mortality. Consequently, blood glucose levels must be safely and effectively controlled, that is, maintained within a normal range, avoiding hypoglycemia on the one hand and elevated glucose concentrations on the other. To accomplish this aim, insulin is often required, avoiding protocols designed to achieve tight glycemic control. To prevent hyperglycemia and its associated complications, energy intake should be adjusted to patients' requirements, avoiding overnutrition and excessive glucose intake. Protein intake should be adjusted to the degree of metabolic stress. Whenever patients require artificial feeding, the enteral route, if not contraindicated, should be used since parenteral nutrition is associated with a higher frequency of hyperglycemia and greater insulin requirements. Enteral nutrition should be administered early, preferably within the first 24 hours of admission to the intensive care unit, after hemodynamic stabilization. Specific diets for hyperglycemia, containing low glycemic index carbohydrates and fibre and enriched with monounsaturated fatty acids, can achieve good glycemic control with lower insulin requirements. PMID- 22309754 TI - [Guidelines for specialized nutritional and metabolic support in the critically ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC SENPE): oncohematological patient]. AB - Patients with cancer, irrespective of the stage of their disease, can require admission to the intensive care unit as a result of the complications of their underlying process or the surgical or pharmacological treatment provided. The cancer itself, as well as the critical status that can result from the complications of the disease, frequently lead to a high degree of hypermetabolism and inadequate energy intake, causing a high incidence of malnutrition in these patients. Moreover, cancer causes anomalous use of nutritional substrates and therefore the route of administration and proportion and intake of nutrients may differ in these patients from those in non-cancer patients. PMID- 22309755 TI - [Guidelines for specialized nutritional and metabolic support in the critically ill-patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC SENPE): obese patient]. AB - As a response to metabolic stress, obese critically-ill patients have the same risk of nutritional deficiency as the non-obese and can develop protein-energy malnutrition with accelerated loss of muscle mass. The primary aim of nutritional support in these patients should be to minimize loss of lean mass and accurately evaluate energy expenditure. However, routinely-used formulae can overestimate calorie requirements if the patient's actual weight is used. Consequently, the use of adjusted or ideal weight is recommended with these formulae, although indirect calorimetry is the method of choice. Controversy surrounds the question of whether a strict nutritional support criterion, adjusted to the patient's requirements, should be applied or whether a certain degree of hyponutrition should be allowed. Current evidence suggested that hypocaloric nutrition can improve results, partly due to a lower rate of infectious complications and better control of hyperglycemia. Therefore, hypocaloric and hyperproteic nutrition, whether enteral or parenteral, should be standard practice in the nutritional support of critically-ill obese patients when not contraindicated. Widely accepted recommendations consist of no more than 60-70% of requirements or administration of 11-14 kcal/kg current body weight/day or 22-25 kcal/kg ideal weight/day, with 2-2.5 g/kg ideal weight/day of proteins. In a broad sense, hypocaloric-hyperprotein regimens can be considered specific to obese critically ill patients, although the complications related to comorbidities in these patients may require other therapeutic possibilities to be considered, with specific nutrients for hyperglycemia, acute respiratory distress syndrome (ARDS) and sepsis. However, there are no prospective randomized trials with this type of nutrition in this specific population subgroup and the available data are drawn from the general population of critically-ill patients. Consequently, caution should be exercised when interpreting these data. PMID- 22309756 TI - [Guidelines for specialized nutritional and metabolic support in the critically ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC SENPE): critically-burned patient]. AB - The response to severe burns is characterized by hypermetabolism (the most hypermetabolic existing model of aggression) and hypercatabolism, with a high degree of destruction of the skeletal musculature. Metabolic disorders are most evident in the first two weeks after the burn, although they can be prolonged in direct relation to the complications that these patients develop. Nutritional metabolic support is an essential part of the treatment of these patients and should be started early, preferentially through the enteral route, with parenteral nutrition as complementary support. Exact calculation of calorie protein requirements in these patients is difficult, even when indirect calorimetry is used, due to the high loss of proteins and CO(2) through the skin. Specific pharmaconutrients are indicated, with a high dose of micronutrients. The use of drugs or medications with anabolic effects is also sometimes indicated. PMID- 22309757 TI - [Guidelines for specialized nutritional and metabolic support in the critically ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC SENPE): patient with polytrauma]. AB - Patients with polytrauma can be viewed as paradigmatic of the critically-ill patient. These previously healthy patients undergo a life-threatening aggression leading to an organic response that is no different from that in other types of patients. The profile of trauma patients has changed and currently corresponds to patients who are somewhat older, with a higher body mass index and greater comorbidity. Severe injuries lead to intense metabolic stress, posing a risk of malnutrition. Therefore, early nutritional support, preferentially through the enteral route, with appropriate protein intake and glutamine supplementation, provides advantages over other routes and types of nutritional formula. To avoid overnutrition, reduced daily calorie intake can be considered in obese patients and in those with medullary lesions. However, little information on this topic is available in patients with medullary lesions. PMID- 22309758 TI - [Guidelines for specialized nutritional and metabolic support in the critically ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC SENPE): patient with sepsis]. AB - Nutritional metabolic management, together with other treatment and support measures used, is one of the mainstays of the treatment of septic patients. Nutritional support should be started early, after initial life support measures, to avoid the consequences of malnutrition, to provide adequate nutritional intake and to prevent the development of secondary complications such as superinfection or multiorgan failure. As in other critically-ill patients, when the enteral route cannot be used to ensure calorie-protein requirements, the association of parenteral nutrition has been shown to be safe in this subgroup of patients. Studies evaluating the effect of specific pharmaconutrients in septic patients are scarce and are insufficient to allow recommendations to be made. To date, enteral diets with a mixture of substrates with distinct pharmaconutrient properties do not seem to be superior to standard diets in altering the course of sepsis, although equally there is no evidence that these diets are harmful. There is insufficient evidence to recommend the use of glutamine in septic patients receiving parenteral nutrition. However, given the good results and absence of glutamine-related adverse effects in the various studies performed in the general population of critically-ill patients, these patients could benefit from the use of this substance. Routine use of omega-3 fatty acids cannot be recommended until further evidence has been gathered, although the use of lipid emulsions with a high omega-6 fatty acid content should be avoided. Septic patients should receive an adequate supply of essential trace elements and vitamins. Further studies are required before the use of high-dose selenium can be recommended. PMID- 22309759 TI - [Guidelines for specialized nutritional and metabolic support in the critically ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC SENPE): neurocritical patient]. AB - Neurocritical patients require specialized nutritional support due to their intense catabolism and prolonged fasting. The preferred route of nutrient administration is the gastrointestinal route, especially the gastric route. Alternatives are the transpyloric route or mixed enteral-parenteral nutrition if an effective nutritional volume of more than 60% cannot be obtained. Total calore intake ranges from 20-30 kcal/kg/day, depending on the period of the clinical course, with protein intake higher than 20% of total calories (hyperproteic diet). Nutritional support should be initiated early. The incidence of gastrointestinal complications is generally higher to other critically-ill patients, the most frequent complication being an increase in gastric residual volume. As in other critically-ill patients, glycemia should be closely monitored and maintained below 150 mg/dL. PMID- 22309761 TI - Purification and characterization of a novel beta-1,3-1,4-glucanase (lichenase) from thermophilic Rhizomucor miehei with high specific activity and its gene sequence. AB - Production, purification, and characterization of a novel beta-1,3-1,4-glucanase (lichenase) from thermophilic Rhizomucor miehei CAU432 were investigated. High level extracellular beta-1,3-1,4-glucanase production of 6230 U/mL was obtained when oat flour (3%, w/v) was used as a carbon source at 50 degrees C. The crude enzyme was purified to homogeneity with a specific activity of 28818 U/mg. The molecular weight of purified enzyme was estimated to be 35.4 kDa and 33.7 kDa by SDS-PAGE and gel filtration, respectively. The optimal pH and temperature of the enzyme were pH 5.5 and 60 degrees C, respectively. The K(m) values of purified beta-1,3-1,4-glucanase for barley beta-glucan and lichenan were 2.0 mM and 1.4 mM, respectively. Furthermore, the gene (RmLic16A) encoding the beta-1,3-1,4 glucanase was cloned and its deduced amino acid sequence showed the highest identity (50%) to characterized beta-1,3-1,4-glucanase from Paecilomyces thermophila. The high-level production and biochemical properties of the enzyme enable its potential industrial applications. PMID- 22309760 TI - [Guidelines for specialized nutritional and metabolic support in the critically ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC SENPE): cardiac patient]. AB - Patients with cardiac disease can develop two types of malnutrition: cardiac cachexia, which appears in chronic congestive heart failure, and malnutrition due to the complications of cardiac surgery or any other type of surgery in patients with heart disease. Early enteral nutrition should be attempted if the oral route cannot be used. When cardiac function is severely compromised, enteral nutrition is feasible, but supplementation with parenteral nutrition is sometimes required. Sustained hyperglycemia in the first 24 hours in patients admitted for acute coronary syndrome, whether diabetic or not, is a poor prognostic factor for 30 day mortality. In critically-ill cardiac patients with stable hemodynamic failure, nutritional support of 20-25 kcal/kg/day is effective in maintaining adequate nutritional status. Protein intake should be 1.2*-1.5 g/kg/day. Routine polymeric or high protein formulae should be used, according to the patient's prior nutritional status, with sodium and volume restriction according to the patient's clinical situation. The major energy source for myocytes is glutamine, through conversion to glutamate, which also protects the myocardial cell from ischemia in critical situations. Administration of 1 g/ day of omega-3 (EPA+DHA) in the form of fish oil can prevent sudden death in the treatment of acute coronary syndrome and can also help to reduce hospital admission for cardiovascular events in patients with chronic heart failure. PMID- 22309762 TI - Rorschach Comprehensive System data from a sample of 211 nonpatient children in Brazil. AB - This study provides Rorschach Comprehensive System normative data for Brazilian boys and girls drawn from public and private schools. Initially, the Child Behavior Checklist was administered to parents to assess the child's social competence and to screen out behavioral disturbances. Afterward, the Raven's Color Progressive Matrices was administered to exclude children with low intellectual development. Finally, the Rorschach Comprehensive System was administered to the selected 211 children who were distributed in 4 subgroups: 7 year-olds (n = 50), 8-year-olds (n = 53), 9-year-olds (n = 52), and 10-year-olds (n = 56). Interrater reliability statistics were calculated, including percentage of agreement and iota. Descriptive statistics of all variables of the Comprehensive System for each subgroup are presented and contrasted with results from other relevant comparison samples. PMID- 22309763 TI - Field programmable chemistry: integrated chemical and electronic processing of informational molecules towards electronic chemical cells. AB - The topic addressed is that of combining self-constructing chemical systems with electronic computation to form unconventional embedded computation systems performing complex nano-scale chemical tasks autonomously. The hybrid route to complex programmable chemistry, and ultimately to artificial cells based on novel chemistry, requires a solution of the two-way massively parallel coupling problem between digital electronics and chemical systems. We present a chemical microprocessor technology and show how it can provide a generic programmable platform for complex molecular processing tasks in Field Programmable Chemistry, including steps towards the grand challenge of constructing the first electronic chemical cells. Field programmable chemistry employs a massively parallel field of electrodes, under the control of latched voltages, which are used to modulate chemical activity. We implement such a field programmable chemistry which links to chemistry in rather generic, two-phase microfluidic channel networks that are separated into weakly coupled domains. Electric fields, produced by the high density array of electrodes embedded in the channel floors, are used to control the transport of chemicals across the hydrodynamic barriers separating domains. In the absence of electric fields, separate microfluidic domains are essentially independent with only slow diffusional interchange of chemicals. Electronic chemical cells, based on chemical microprocessors, exploit a spatially resolved sandwich structure in which the electronic and chemical systems are locally coupled through homogeneous fine-grained actuation and sensor networks and play symmetric and complementary roles. We describe how these systems are fabricated, experimentally test their basic functionality, simulate their potential (e.g. for feed forward digital electrophoretic (FFDE) separation) and outline the application to building electronic chemical cells. PMID- 22309764 TI - Reusing and composing models of cell fate regulation of human bone precursor cells. AB - In order to treat osteoporosis and other bone mass disorders it is necessary to understand the regulatory processes that control the cell fate decisions responsible for going from bone precursor cells to bone tissue. Many processes interact to regulate cell division, differentiation and apoptosis. There are models for these basic processes, but not for their interactions. In this work we use the theory of switched systems, reuse and composition of validated models to describe the cell fate decisions leading to bone and fat formation. We describe the differentiation of osteo-adipo progenitor cells by composing its model with differentiation stimuli. We use the activation of the Wnt pathway as stimulus to osteoblast lineage, including regulation of cell division and apoptosis. This model is our first step to simulate physiological responses in silico to treatments for bone mass disorders. PMID- 22309765 TI - Accuracy of brain imaging in the diagnosis of idiopathic intracranial hypertension. AB - AIM: To investigate the accuracy of individual and combinations of signs on brain magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) in the diagnosis of idiopathic intracranial hypertension (IIH). MATERIALS AND METHODS: This study was approved by the institutional research ethics board without informed consent. Forty-three patients and 43 control subjects were retrospectively identified. Each patient and control had undergone brain MRI and MRV. Images were anonymized and reviewed by three neuroradiologists, blinded to clinical data, for the presence or absence of findings associated with IIH. The severity of stenosis in each transverse sinus was graded and summed to generate a combined stenosis score (CSS). The sensitivity, specificity, and likelihood ratios (LR) were calculated for individual and combinations of signs. RESULTS: Partially empty sella (specificity 95.3%, p < 0.0001), flattening of the posterior globes (specificity 100%, p < 0.0001), and CSS <4 (specificity 100%, p < 0.0001) were highly specific for IIH. The presence of one sign, or any combination, significantly increased the odds of a diagnosis of IIH (LR+ 18.5 to 46, p < 0.0001). Their absence, however, did not rule out IIH. CONCLUSIONS: Brain MRI with venography significantly increased the diagnostic certainty for IIH if there was no evidence of a mass, hydrocephalus, or sinus thrombosis and one of the following signs was present: flattening of the posterior globes, partially empty sella, CSS <4. However, absence of these signs did not exclude a diagnosis of IIH. PMID- 22309766 TI - Shoulder arthroplasty. Part 2: normal and abnormal radiographic findings. AB - Frequently, the decision made by general practitioners or musculoskeletal triage assessment services to refer patients for specialist review is initiated by a radiological report. Following shoulder arthroplasty it is important to ensure that any patient with asymptomatic evidence of a failing prosthesis is referred for review so that revision surgery can be contemplated and planned before the situation becomes unsalvageable. The first paper in this series described the various types of shoulder arthroplasty and indications for each. This follow-up paper will concentrate on their modes of failure and the associated radiographic features, and is aimed at radiology trainees and non-musculoskeletal specialist radiologists. PMID- 22309768 TI - Determinants of insecticide-treated net ownership and utilization among pregnant women in Nigeria. AB - BACKGROUND: Malaria during pregnancy is a major public health problem in Nigeria leading to increase in the risk of maternal mortality, low birth weight and infant mortality. This paper is aimed at highlighting key predictors of the ownership of insecticide treated nets (ITNs) and its use among pregnant women in Nigeria. METHODS: A total of 2348 pregnant women were selected by a multi-stage probability sampling technique. Structured interview schedule was used to elicit information on socio-demographic characteristics, ITN ownership, use, knowledge, behaviour and practices. Logistic regression was used to detect predictors of two indicators: ITN ownership, and ITN use in pregnancy among those who owned ITNs. RESULTS: ITN ownership was low; only 28.8% owned ITNs. Key predictors of ITN ownership included women who knew that ITNs prevent malaria (OR = 3.85; p < 0001); and registration at antenatal clinics (OR = 1.34; p = 0.003). The use of ITNs was equally low with only 7.5% of all pregnant women, and 25.7% of all pregnant women who owned ITNs sleeping under a net. The predictors of ITN use in pregnancy among women who owned ITNs (N = 677) identified by logistic regression were: urban residence (OR = 1.87; p = 0.001); knowledge that ITNs prevent malaria (OR = 2.93; p < 0001) and not holding misconceptions about malaria prevention (OR = 1.56; p = 0.036). Educational level was not significantly related to any of the two outcome variables. Although registration at ANC is significantly associated with ownership of a bednet (perhaps through free ITN distribution) this does not translate to significant use of ITNs. CONCLUSIONS: ITN use lagged well behind ITN ownership. This seems to suggest that the current mass distribution of ITNs at antenatal facilities and community levels may not necessarily lead to use unless it is accompanied by behaviour change interventions that address the community level perceptions, misconceptions and positively position ITN as an effective prevention device to prevent malaria. PMID- 22309769 TI - Mefloquine interferes with glycolysis in schistosomula of Schistosoma mansoni via inhibition of enolase. AB - The antimalarial drug mefloquine has promising antischistosomal properties killing haematophagous adult schistosomes as well as schistosomula. The mode of action and involved drug targets of mefloquine in Schistosoma mansoni schistosomula are unknown. In order to identify mefloquine-binding proteins and thus potential drug targets, mefloquine affinity chromatography with S. mansoni schistosomula crude extracts was performed. We found one specific mefloquine binding protein that was identified by mass spectrometry as the glycolytic enzyme enolase (Q27877). Enolase activity assays were performed on schistosomula crude extracts and on the recombinant enolase Q27877 expressed in Escherichia coli. In schistosomula crude extracts enolase activity was inhibited by mefloquine and by the enolase inhibitor sodium fluoride, while activity of the recombinant enolase was not affected. In contrast to enolase from crude extracts, recombinant Q27877 did not bind to mefloquine-agarose. Using isothermal microcalorimetry, we next investigated the metabolic inhibition of mefloquine and 3 known glycolytic inhibitors in Schistosoma spp., namely sodium fluoride, 3-bromopyruvate and menadione on schistosomula in the presence or absence of glucose. We found that in the presence of glucose, schistosomula were less affected by mefloquine, sodium fluoride and 3-bromopyruvate, whereas glucose had no protective effect when schistosomula had been exposed to menadione. These results suggest a potential role of mefloquine as an inhibitor of glycolysis, at least in stages where other targets like haem degradation are not relevant. PMID- 22309770 TI - Asthma burden in the United States: results of the 2009 Asthma Insight and Management survey. AB - Updated guidelines and new treatments for asthma have become available since the last major survey of asthma management in the United States was completed ~11 years ago. The Asthma Insight and Management (AIM) survey was conducted to assess the current status of asthma burden in the United States. A geographically stratified screening of 60,682 households provided a national sample of 2500 patients with current asthma (2186 adults aged >=18 years; 314 adolescents aged 12-17 years). A national sample of 1004 adults without current asthma was interviewed for comparison with the adult asthma population, and 309 asthma health care providers were surveyed for their opinions about the burden of asthma. Asthma prevalence in the United States was estimated at 8%. Twice as many adult asthma patients rated their health as "only fair," "poor," or "very poor," or experienced limitations in activity because of health problems, compared with the general population. Asthma also frequently caused negative emotional symptoms in patients. Most patients experienced asthma throughout the year (63%) and symptoms within the 4 weeks before the summer survey (68%). Overall, 41% of patients responded that asthma interfered with their/their child's life "some" or "a lot". During the year before the survey, 69% of patients experienced at least one severe asthma episode. Asthma burden in the United States remains high despite the availability of updated treatment guidelines and new therapies. Asthma care in the United States remains suboptimal, indicating the need for continued improvements in patient management. PMID- 22309771 TI - Human glutaredoxin 3 forms [2Fe-2S]-bridged complexes with human BolA2. AB - Human glutaredoxin 3 (Glrx3) is an essential [2Fe-2S]-binding protein with ill defined roles in immune cell response, embryogenesis, cancer cell growth, and regulation of cardiac hypertrophy. Similar to other members of the CGFS monothiol glutaredoxin (Grx) family, human Glrx3 forms homodimers bridged by two [2Fe-2S] clusters that are ligated by the conserved CGFS motifs and glutathione (GSH). We recently demonstrated that the yeast homologues of human Glrx3 and the yeast BolA like protein Fra2 form [2Fe-2S]-bridged heterodimers that play a key role in signaling intracellular iron availability. Herein, we provide biophysical and biochemical evidence that the two tandem Grx-like domains in human Glrx3 form similar [2Fe-2S]-bridged complexes with human BolA2. UV-visible absorption and circular dichroism, resonance Raman, and electron paramagnetic resonance spectroscopic analyses of recombinant [2Fe-2S] Glrx3 homodimers and [2Fe-2S] Glrx3-BolA2 complexes indicate that the Fe-S coordination environments in these complexes are virtually identical to those of the analogous complexes in yeast. Furthermore, we demonstrate that apo BolA2 binds to each Grx domain in the [2Fe 2S] Glrx3 homodimer forming a [2Fe-2S] BolA2-Glrx3 heterotrimer. Taken together, these results suggest that the unusual [2Fe-2S]-bridging Grx-BolA interaction is conserved in higher eukaryotes and may play a role in signaling cellular iron status in humans. PMID- 22309772 TI - Hospital Incident Command System (HICS) performance in Iran; decision making during disasters. AB - BACKGROUND: Hospitals are cornerstones for health care in a community and must continue to function in the face of a disaster. The Hospital Incident Command System (HICS) is a method by which the hospital operates when an emergency is declared. Hospitals are often ill equipped to evaluate the strengths and vulnerabilities of their own management systems before the occurrence of an actual disaster. The main objective of this study was to measure the decision making performance according to HICS job actions sheets using tabletop exercises. METHODS: This observational study was conducted between May 1st 2008 and August 31st 2009. Twenty three Iranian hospitals were included. A tabletop exercise was developed for each hospital which in turn was based on the highest probable risk. The job action sheets of the HICS were used as measurements of performance. Each indicator was considered as 1, 2 or 3 in accordance with the HICS. Fair performance was determined as < 40%; intermediate as 41-70%; high as 71-100% of the maximum score of 192. Descriptive statistics, T-test, and Univariate Analysis of Variance were used. RESULTS: None of the participating hospitals had a hospital disaster management plan. The performance according to HICS was intermediate for 83% (n = 19) of the participating hospitals. No hospital had a high level of performance. The performance level for the individual sections was intermediate or fair, except for the logistic and finance sections which demonstrated a higher level of performance. The public hospitals had overall higher performances than university hospitals (P = 0.04). CONCLUSIONS: The decision making performance in the Iranian hospitals, as measured during table top exercises and using the indicators proposed by HICS was intermediate to poor. In addition, this study demonstrates that the HICS job action sheets can be used as a template for measuring the hospital response. Simulations can be used to assess preparedness, but the correlation with outcome remains to be studied. PMID- 22309773 TI - Application of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to the pharmacokinetics, tissue distribution and excretion studies of felotaxel (SHR110008) in tumor-bearing mice. AB - Felotaxel (SHR110008), currently under clinical investigation in phase I trial, is a new effective taxane with greater anticancer activity and less toxicity than docetaxel. Pharmacokinetic studies in animal models are the important components in clinical development of this agent. In this study, a rapid and sensitive analytical method based on high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of felotaxel in tumor-bearing mice plasma, urine, feces and tissues (brain, heart, liver, lung and kidney and tumor). For all matrices, sample preparation involved liquid liquid extraction with ethyl acetate. Calibration curves (1/x2 weighted) offered satisfactory linearity (r2 >= 0.995) within the test range. The lower limit of quantitation (LLOQ) for all matrices was 10 ng/ml except that for mouse plasma and brain LLOQ was 1 ng/ml. The accuracy and precision ranged from 86.1 to 107.2% and 1.1 to 9.2%, respectively. Recoveries (73.9-96.1%) and matrix effects (76.4 97.2%) were satisfactory in all the biological matrices examined. Stability studies (85.1-101.5%) showed that felotaxel was stable both during the assay procedure and long-term storage. The assay was successfully applied to plasma pharmacokinetics, tissue distribution and excretion study of mice. The pharmacokinetic parameters, such as half-life, mean residence time, maximum concentration were determined. The preclinical data are useful for the design of clinical trials of felotaxel. PMID- 22309774 TI - Quantification of melamine in human urine using cation-exchange based high performance liquid chromatography tandem mass spectrometry. AB - Melamine and cyanuric acid have been implicated as adulterants in baby formula in China and pet foods in North America. In China, the effect of melamine or melamine-cyanuric acid adulteration lead to kidney stone development and acute renal failure in thousands of Chinese infants. A selective and sensitive analytical method was developed to measure melamine in human urine in order to evaluate the extent of potential health implications resulting from the consumption of these types of adulterated products in the general US population. This method involves extracting melamine from human urine using cation-exchange solid-phase extraction, chromatographically separating it from its urinary matrix co-extractants on a silica-based, strong-cation exchange analytical column using high performance liquid chromatography, and analysis using positive mode electrospray ionization tandem mass spectrometry. Quantification was performed using modified, matrix-based isotope dilution calibration covering the concentration range of 0.50-100 ng/mL. The limit of detection, calculated using replicates of blank and low level spiked samples, was 0.66 ng/mL and the relative standard deviations were between 6.89 and 14.9%. The relative recovery of melamine was 101-106%. This method was tested for viability by analyzing samples collected from the general US population. Melamine was detected in 76% of the samples tested, with a geometric mean of 2.37 ng/mL, indicating that this method is suitable for reliably detecting background exposures to melamine or other chemicals from which it can be derived. PMID- 22309775 TI - A new way to fast and high resolution determination of modified nucleosides. AB - The abnormal concentration of several modified nucleosides in the urine is supposed to be marker of carcinogenesis. For this reason analytical methods useful in the determination of these compounds in biological samples are of great importance. Present study concerns the application of Ultra High Performance Liquid Chromatography for fast, precise, high resolution separation and quantification of eight modified nucleosides in the synthetic serum and urine samples. The systematic study concerning the retention behavior of analyzed nucleosides on various stationary and mobile phases was performed. The attempt to apply four different column packings (octedecyl, octyl, phenyl, siliga gel) of different particle sizes and various mobile phases was made. On the basis of obtained results Kinetex C18 column and methanol/water mixtures were chosen for the utilization in biological samples. Developed method allows separation and quantification of eight modified nucleosides in serum or urine during 4min with good linearity, accuracy and low LOQ values. PMID- 22309776 TI - Development and validation of LC-MS/MS assays for the quantification of E7080 and metabolites in various human biological matrices. AB - To support clinical pharmacokinetic studies with the anticancer agent E7080 (lenvatinib), liquid chromatography tandem mass spectrometry (LC-MS/MS) methods were developed for the quantification of E7080 and four of its metabolites in human plasma, urine and faeces and of E7080 in whole blood. Cross-analyte interferences between metabolites and parent compound were expected and therefore accounted for early in the method development. Plasma, urine and faeces samples were extracted with acetonitrile. Chromatographic separation was achieved on a 50 mm * 2.1 mm I.D. XTerra MS C18 column, with a 0.2 mL/min flow and gradient elution starting with 100% formic acid in water, followed by an increasing percentage of acetonitrile. Whole blood samples were extracted with diethyl ether and extracts were injected on a 150 mm * 2.1mm I.D. Symmetry Shield RP8 column. Detection was performed using an API3000 triple quadrupole mass spectrometer, with a turbo ion spray interface, operating in positive ion mode. Using 250 MUL of plasma, E7080 and its metabolites could be quantified between 0.25 and 50.0ng/mL. The quantifiable ranges of E7080 in whole blood, urine and faeces were 0.25-500 ng/mL, 1.00-500 ng/mL and 0.1-25MUg/g, using sample volumes of 250 MUL, 200 MUL and 250 mg, respectively. Calibration curves in all matrices were linear with a correlation coefficient (r(2)) of 0.994 or better. At the lower limit of quantification, accuracies were within +/-20% of the nominal concentration with CV values less than 20%. At the other concentrations the accuracies were within +/-15% of the nominal concentration with CV values below 15%. The developed methods have successfully been applied in a mass balance study of E7080. PMID- 22309777 TI - Concanavalin A immobilized poly(ethylene glycol dimethacrylate) based affinity cryogel matrix and usability of invertase immobilization. AB - Concanavalin A (Con A) immobilized supermacroporous poly(ethylene glycol dimethacrylate) [poly(EGDMA)] monolithic cryogel column was prepared by radical cryocopolymerization of EGDMA as a monomer and N,N'-methylene-bisacrylamide as a crosslinker. Bioligand Con A was then immobilized by covalent binding onto poly(EGDMA) cryogel via glutaraldehyde activation [Con A-poly(EGDMA)]. Con A poly(EGDMA) cryogel was characterized by swelling studies and scanning electron microscopy. The monolithic cryogel contained a continuous polymeric matrix having interconnected pores of 10-50 MUm size. The equilibrium swelling degree of the cryogel was 15.01 g H2O/g dry cryogel. Con A-poly(EGDMA) cryogel was used in the adsorption/desorption of invertase from aqueous solutions. The maximum amount of invertase adsorption from aqueous solution in acetate buffer was 55.45 mg/g polymer at pH 5.0. Con A-poly(EGDMA) cryogels were used for repetitive adsorption/desorption of invertase without noticeable loss in invertase adsorption capacity after 10 cycles. PMID- 22309778 TI - Cellular FLICE-like inhibitory proteins (c-FLIPs): fine-tuners of life and death decisions. AB - c-FLIP proteins (isoforms: c-FLIP(L), c-FLIP(S), and c-FLIP(R)) play an essential role in the regulation of death receptor (DR)-induced apoptosis and NF-kappaB activation. Here, we discuss multiple mechanisms by which c-FLIPs control NF kappaB activation and the life/death decision made in cancer and immune cells. We focus on the role of c-FLIP in cellular signaling. We concentrate on c-FLIP protein modifications as well as on the regulation of c-FLIP expression levels. Furthermore, we discuss in detail how the exact quantity and dynamics of different c-FLIP isoforms in the cell influence the induction of pro- versus anti apoptotic pathways. PMID- 22309779 TI - Epithelial cells utilize cortical actin/myosin to activate latent TGF-beta through integrin alpha(v)beta(6)-dependent physical force. AB - Transforming Growth Factor Beta (TGF-beta) is involved in regulating many biological processes and disease states. Cells secrete cytokine as a latent complex that must be activated for it to exert its biological functions. We previously discovered that the epithelial-restricted integrin alpha(v)beta(6) activates TGF-beta and that this process is important in a number of in vivo models of disease. Here, we show that agonists of G-protein coupled receptors (Sphingosine-1-Phosphate and Lysophosphatidic Acid) which are ligated under conditions of epithelial injury directly stimulate primary airway epithelial cells to activate latent TGF-beta through a pathway that involves Rho Kinase, non muscle myosin, the alpha(v)beta(6) integrin, and the generation of mechanical tension. Interestingly, lung epithelial cells appear to exert force on latent TGF beta using sub-cortical actin/myosin rather than the stress fibers utilized by fibroblasts and other traditionally "contractile" cells. These findings extend recent evidence suggesting TGF-beta can be activated by integrin-mediated mechanical force and suggest that this mechanism is important for an integrin (alpha(v)beta(6)) and a cell type (epithelial cells) that have important roles in biologically relevant TGF-beta activation in vivo. PMID- 22309780 TI - Intraluminal migration of a spacer with small bowel obstruction: a case report of rare complication. AB - The spacer placement is a prevalent procedure to separate the surrounding normal tissues from locally recurrent rectal tumor before the application of radiotherapy. However, complications could occur due to the foreign nature of the spacer. This report describes a case of 60-year-old man who had undergone radiotherapy two years earlier for a recurrent rectal tumor and presented with small bowel obstruction. A spacer was used before radiotherapy. Radiological assessment and laparotomy revealed the presence of the spacer inside the small bowel lumen. It is possible that the spacer established contact with the intestine, elicited local inflammatory reaction that facilitated the complete penetration of the intestinal wall without causing any clinical symptoms. PMID- 22309781 TI - Protein-phytate interactions in pig and poultry nutrition: a reappraisal. AB - Protein-phytate interactions are fundamental to the detrimental impact of phytate on protein/amino acid availability. The inclusion of exogenous phytase in pig and poultry diets degrades phytate to more innocuous esters and attenuates these negative influences. The objective of the present review is to reappraise the underlying mechanisms of these interactions and reassess their implications in pig and poultry nutrition. Protein digestion appears to be impeded by phytate in the following manner. Binary protein-phytate complexes are formed at pH levels less than the isoelectric point of proteins and complexed proteins are refractory to pepsin digestion. Once the protein isoelectric points are exceeded binary complexes dissociate; however, the isoelectric point of proteins in cereal grains may be sufficiently high to permit these complexes to persist in the small intestine. Ternary protein-phytate complexes are formed at pH levels above the isoelectric point of proteins where a cationic bridge links the protein and phytate moieties. The molecular weights of protein and polypeptides in small intestinal digesta may be sufficient to allow phytate to bind nutritionally important amounts of protein in ternary complexes. Thus binary and ternary complexes may impede protein digestion and amino acid absorption in the small intestine. Alternatively, phytate may interact with protein indirectly. Myo inositol hexaphosphate possesses six phosphate anionic moieties (HPO(4)(2-)) that have strong kosmotropic effects and can stabilise proteins by interacting with the surrounding water medium. Phytate increases mucin secretions into the gut, which increases endogenous amino acid flows as the protein component of mucin remains largely undigested. Phytate promotes the transition of Na(+) into the small-intestinal lumen and this suggests that phytate may interfere with glucose and amino acid absorption by compromising Na(+)-dependent transport systems and the activity of the Na pump (Na(+)-K(+)-ATPase). Starch digestion may be depressed by phytate interacting with proteins that are closely associated with starch in the endosperm of cereal grains. While elucidation is required, the impacts of dietary phytate and exogenous phytase on the site, rate and synchrony of glucose and amino acid intestinal uptakes may be of importance to efficient protein deposition. Somewhat paradoxically, the responses to phytase in the majority of amino acid digestibility assays in pigs and poultry are equivocal. A brief consideration of the probable reasons for these inconclusive outcomes is included in this reappraisal. PMID- 22309782 TI - Radiofrequency ablation of incidental benign small renal mass: outcomes and follow-up protocol. AB - OBJECTIVE: To review our 10-year experience with radiofrequency ablation, focusing on the outcomes for the incidental benign renal tumor. Tumor ablation is an alternative minimally invasive approach for the treatment of small renal masses (SRMs), with published series appropriately emphasizing the outcomes for the renal cell carcinoma subset of treated tumors. However, just as with partial nephrectomy, approximately 20% of SRMs are benign. The intermediate- to long-term outcome of the incidentally ablated benign tumor and its appropriate follow-up protocol is unknown. METHODS: All SRMs treated with temperature-based radiofrequency ablation from 2001 to 2011 were reviewed. Of a total of 280 enhancing SRMs biopsied at radiofrequency ablation, 47 were confirmed as benign tumors. Ablation success was defined as the lack of enhancement on the initial postablation axial imaging. Recurrence was defined as tumor growth and enhancement on follow-up axial imaging. RESULTS: Of the 47 benign tumors, 32 were treated percutaneously and 15 laparoscopically. The histologic biopsy finding was angiomyolipoma in 10 and oncocytoma in 37. The median tumor size was 2 cm (range 1-3.6), and the mean follow-up was 45 months. No recurrences developed, and all lesions required only 1 treatment session. The median pre- and postoperative glomerular filtration rate was 77 mL/min/1.73 m(2) (range 39-137) and 68 mL/min/1.73 m(2) (range 36-137). The present study was limited by its retrospective nature and small sample population. CONCLUSION: Radiofrequency ablation of SRMs <3.5 cm found to be benign on concurrent biopsy can be efficaciously treated with a single treatment session. Long-term follow-up imaging might not be required if successful ablation is determined at the initial post-treatment cross-sectional imaging study. PMID- 22309783 TI - The augmented nontransected anastomotic urethroplasty for the treatment of bulbar urethral strictures. AB - OBJECTIVE: The augmented anastomotic urethroplasty (AAU) combines resection of a urethral stricture and an onlay graft. The augmented nontransected anastomotic urethroplasty (ANTA) is a modification of the AAU and involves complete stricture excision without transecting the spongiosum. MATERIALS AND METHODS: This is a retrospective cohort study comparing ANTA with dorsal onlay buccal grafting (DOBG) for bulbar urethral strictures. Medical records between 2005 and 2010 were reviewed. A cross-sectional questionnaire was used to assess long-term outcomes. Medians and interquartile ranges are reported. RESULTS: Forty-four men (23 DOBG, 21 ANTA) with a median follow-up of 2.3 years (range 1.2-3.8) were identified. There were no significant differences between ANTA patients and DOBG patients in terms of age, previous treatment, stricture location, or postoperative follow-up. There was no significant difference between groups in the use of bilateral buccal grafts (P = .416); median buccal length harvested was significantly less in the ANTA group (4.5 cm [range 4.0-5.0]) vs the DOBG group (5.0 cm [range 5.0-8.0], P = .047). Response rate to the cross-sectional survey was 59%. Five patients reported postoperative donor site complications, and there were no significant differences between the ANTA and DOBG groups. Overall success was 93% and not statistically different between groups (log rank test, P = .548). One ANTA patient and 2 DOBG patients required posturethroplasty treatment. CONCLUSIONS: The ANTA has results similar to DOBG and appears to be a viable option in the treatment of bulbar urethral strictures. This technique allows the surgeon to avoid urethral transection, to reconfigure the width of the urethral plate, and to use a smaller buccal graft. PMID- 22309784 TI - Efficacy of gabapentin for prevention of postoperative catheter-related bladder discomfort in patients undergoing transurethral resection of bladder tumor. AB - OBJECTIVE: To evaluate the effect of 600 mg and 1200 mg oral gabapentin pretreatment for the prevention of postoperative catheter-related bladder discomfort (CRBD) in patients undergoing catheterization after transurethral resection of bladder tumor (TURBT). MATERIALS AND METHODS: One hundred adult patients undergoing elective TURBT under spinal anesthesia were randomly allocated into 3 groups. Group I patients received placebo, group II patients received 600 mg gabapentin, and group III patients received 1200 mg gabapentin 1 hour before surgery. Lumber subarachnoid block was administered with 2.5 mL 0.5% hyperbaric bupivacaine. The patients were observed for the incidence and severity of CRBD in the postoperative period. RESULTS: The incidence of CRBD was 90% in group I, 66% in group II, and 26% in group III. The incidence of bladder discomfort was significantly low in group III at all time points compared with group I and at 4, 6, 12, and 24 hours compared with group II. The severity of CRBD was also less in group II and III patients compared with group I. Fifteen patients in group I developed moderate discomfort, whereas 1 patient in group II and none in group III. None of the patient receiving gabapentin had severe discomfort. The duration and level of sensory and motor block was comparable among groups. One patient in group II and 2 patients in group III were complained of dizziness in postoperative period. CONCLUSION: Gabapentin 1200 mg administered before surgery is more effective than gabapentin 600 mg in decreasing the incidence of postoperative CRBD. PMID- 22309785 TI - Editorial comment. PMID- 22309786 TI - Long-term outcomes of percutaneous nephrolithotomy in patients with chronic kidney disease: a single-center experience. AB - OBJECTIVE: To present our long-term follow-up data from patients with kidney stones and chronic kidney disease to identify the factors that could help predict the likelihood of long-term deterioration in renal function. METHODS: From January 2002 to July 2010, we performed 1117 percutaneous nephrolithotomy (PNL) procedures in 1051 patients. We retrospectively analyzed 69 PNL procedures for 67 patients (47 men and 20 women) in whom the estimated glomerular filtration rate (eGFR) was <60 mL/min/1.73 m(2). Two outcomes were measured. The percentage of change in the eGFR was measured comparing the preoperative and postoperative values. A 5% change in renal function was arbitrarily chosen to divide the population into 3 groups: group 1, an eGFR change of <= 5%; group 2, an eGFR increase of >5%; and group 3, an eGFR decrease of <5%. The second outcome measure was the presence of chronic kidney disease progressing in the first and consecutive years. RESULTS: The mean patient age was 57 +/- 14.1 years. The complication rate was 23.1% using the Clavien classification. The mean follow-up time was 45.7 +/- 17.08 months. The mean eGFR before and after PNL was 37.9 +/- 14.05 and 45.1 +/- 16.8, respectively. Diabetes mellitus (odds ratio 15.82, P = .036) and urinary infection (odds ratio 10.6, P = .04) were predictive of renal function deterioration at 1 year on multivariate analysis. CONCLUSION: PNL in patients with chronic kidney disease is safe and results in renal function preservation for a 5-year period. Diabetes mellitus and urinary infection were independent predictive of renal function impairment. Therefore, patients with diabetes mellitus and urinary tract infection should be followed up carefully and informed about hazardous potential of those diseases. PMID- 22309787 TI - Usefulness of sum of the thickness of plaque in the carotid artery for predicting the presence and the extent of the coronary artery disease in patients with type 2 diabetes mellitus without known coronary artery disease. AB - AIMS: The usefulness of the sum of plaque thickness in the carotid artery (plaque score; PS), as a prediction of coronary artery disease (CAD) was investigated in patients with type 2 diabetes mellitus. METHODS: B mode ultrasonographic scanning of the carotid artery and multislice computed tomography (MSCT) coronary angiography were performed in 227 diabetic patients without known cardiac disease. RESULTS: The PS was useful to predict the presence of diseased [nonobstructive and obstructive] CAD (?3 segments) and obstructive (?50%) CAD with cut-off value of 3.5mm (area under curve: 0.745 and 0.782, respectively), according to a receiver operating characteristics curve analysis. A multivariate logistic analysis of baseline risk factors showed that the PS was independent risk factor for the prediction of diseased and obstructive coronary artery disease (R(2)=0.2165, p<0.0001 and R(2)=0.2265, p<0.0001, respectively). The PS was most significant predictor of the number of diseased and obstructive segments of the coronary artery in a multiple regression analysis (R(2)=0.2022, p<0.0001 and R(2)=0.2209, p<0.0001, respectively). CONCLUSIONS: The PS in the carotid artery was useful for the prediction of the presence and the extent of CAD, and was most important as a screening test for the identification of a high risk group of asymptomatic diabetic patients. PMID- 22309788 TI - Association between vitamin D status and metabolic syndrome risk among Korean population: based on the Korean National Health and Nutrition Examination Survey IV-2, 2008. AB - AIMS: Low serum 25-hydroxyvitamin D (25(OH)D) levels have been linked to metabolic syndrome. However, community-based data for healthy Korean individuals are lacking. We aimed to assess the vitamin D status and the association of 25(OH)D deficiency with metabolic syndrome in the South Korean population (latitude 33-38 degrees N). METHODS: In this population-based study, we assessed 5559 South Korean adults selected from the Korean National Health and Nutrition Examination Survey IV-2, 2008. We used multiple logistic regression analysis to assess the association between vitamin D deficiency and metabolic syndrome. RESULTS: The prevalence of vitamin D deficiency (<20 ng/mL) was 56.0%. Subjects with vitamin D deficiency were younger and had higher education, lower physical activity, and lower alcohol consumption than those with normal vitamin D levels. The overall risk of metabolic syndrome was not associated with 25(OH)D concentration. The adjusted OR of reduced high density lipoprotein cholesterol (HDL-C) decreased across the quintiles of 25(OH)D concentrations (OR=0.72; 95% confidence interval=0.54-0.95 for comparisons of lowest vs. highest quintile; P for trend=0.003). CONCLUSIONS: A high prevalence of vitamin D deficiency was noted in the general South Korean population. Serum 25(OH)D concentration was inversely associated with the risk of having reduced HDL-C. PMID- 22309789 TI - Zebra mussel adhesion: structure of the byssal adhesive apparatus in the freshwater mussel, Dreissena polymorpha. AB - The freshwater zebra mussel (Dreissena polymorpha) owes a large part of its success as an invasive species to its ability to attach to a wide variety of substrates. As in marine mussels, this attachment is achieved by a proteinaceous byssus, a series of threads joined at a stem that connect the mussel to adhesive plaques secreted onto the substrate. Although the zebra mussel byssus is superficially similar to marine mussels, significant structural and compositional differences suggest that further investigation of the adhesion mechanisms in this freshwater species is warranted. Here we present an ultrastructural examination of the zebra mussel byssus, with emphasis on interfaces that are critical to its adhesive function. By examining the attached plaques, we show that adhesion is mediated by a uniform electron dense layer on the underside of the plaque. This layer is only 10-20 nm thick and makes direct and continuous contact with the substrate. The plaque itself is fibrous, and curiously can exhibit either a dense or porous morphology. In zebra mussels, a graded interface between the animal and the substrate mussels is achieved by interdigitation of uniform threads with the stem, in contrast to marine mussels, where the threads themselves are non uniform. Our observations of several novel aspects of zebra mussel byssal ultrastructure may have important implications not only for preventing biofouling by the zebra mussel, but for the development of new bioadhesives as well. PMID- 22309790 TI - Accelerated partial breast irradiation using once-daily fractionation: analysis of 312 cases with four years median follow-up. AB - BACKGROUND: There are limited data on accelerated partial breast irradiation (APBI) using external beam techniques. Moreover, there are recent reports of increased fibrosis and unacceptable cosmesis with APBI using external beam with BID fractionation. We adopted a once daily regimen of APBI with fractionation similar to that shown to be effective in a Canadian randomized trial of whole breast irradiation. It is unclear whether patients with DCIS or invasive lobular carcinoma (ILC) are suitable for APBI. METHODS: The retrospective cohort included 310 patients with 312 tumors of T1-T2N0-N1micM0 invasive ductal carcinoma (IDC), ILC, or Tis (DCIS) treated with APBI via external beam. Most patients were treated using IMRT with 16 daily fractions of 270 cGy to a dose of 4320 cGy. The target volume included the lumpectomy cavity plus 1.0 cm to account for microscopic disease and an additional 0.5 to 1.0 cm for setup uncertainty and breathing motion. Ipsilateral breast failure (IBF) was pathologically confirmed as a local failure (LF) or an elsewhere failure (EF). RESULTS: Median follow-up was 49 months. Among the 312 cases, 213 were IDC, 31 ILC, and 68 DCIS. Median tumor size was 1.0 cm. There were 9 IBFs (2.9%) including 5 LFs and 4 EFs. The IBF rates among patients with IDC, ILC, and DCIS were 2.4%, 3.2%, and 4.4%, respectively, with no significant difference between histologies. When patients were analyzed by the ASTRO APBI consensus statement risk groups, 32% of treated cases were considered suitable, 50% cautionary, and 18% unsuitable. The IBF rates among suitable, cautionary, and unsuitable patients were 4.0%, 2.6%, and 1.8%, respectively, with no significant difference between risk groups. Acute skin reactions were rare and long-term cosmetic outcome was very good to excellent. CONCLUSIONS: External beam APBI with once daily fractionation has a low rate of IBF consistent with other published APBI studies. The ASTRO risk stratification did not differentiate a subset of patients with a higher rate of IBF. APBI may be an appropriate treatment for women with DCIS and ILC. PMID- 22309791 TI - Neural mechanisms of risk taking and relationships with hazardous drinking. AB - BACKGROUND: Impulsivity, particularly risk taking, is believed to play a significant role in alcohol use disorders (AUDs). While risk taking has been measured using questionnaires, recent performance-based tasks such as the Balloon Analog Risk Task (BART) have shown considerable promise in understanding risky decision-making processes in drinkers. While the number of studies using the BART has grown significantly over the past decade, the neural mechanisms that underlie risky choices on the BART have only begun to be explored. The current study was designed to assess both the neural mechanisms of risk taking on the BART and to explore relationships between risk taking and hazardous drinking. METHODS: Seventy-nine individuals with an AUD completed an fMRI compatible version of the BART that required pumping simulated air into risky or nonrisky balloons to earn points on each trial, and deciding when to terminate pumping to earn points accumulated. Hazardous drinking was assessed with the Alcohol Use Disorder Identification Test (AUDIT). RESULTS: Comparison of risky and nonrisky decisions revealed differences in the dorsal anterior cingulate cortex (dACC), anterior insula, and striatum. Comparison of Cashout responses and Explosions revealed increased responses in lateral prefrontal cortex, insula, ACC, and middle temporal gyrus during Explosions and greater response in inferior parietal lobe and caudate during Cashouts. When examining relationships between hazardous drinking and neural measures of risk taking, we found significant negative relationships with insula, striatum, and dACC. CONCLUSIONS: The current results suggest that risk taking is associated with increased response in the dACC and anterior insula, regions previously implicated in representing error likelihood and negative outcome magnitudes, respectively. In addition, hazardous drinking was associated with responses in the dACC, possibly suggesting a reduced ability to predict the likelihood of errors and to predict negative outcomes associated with risk taking. PMID- 22309792 TI - Protective emotional regulation processes towards adjustment in infertile patients. AB - Little is known about emotional regulation processes of psychological flexibility/acceptance, self-compassion, and coping styles in infertility and the way they may exert a protective function towards depression. The aim of the current study was to explore how these emotion regulation processes are related to depression and to the sense of self-efficacy to deal with infertility in infertile patients. Gender differences were also considered. One hundred couples without known fertility problems and 100 couples with an infertility diagnosis completed the instruments: Beck Depression Inventory, Coping Styles Questionnaire, Acceptance and Action Questionnaire, Self-Compassion Scale and Infertility Self-efficacy Scale. Infertile couples presented statistically significantly higher scores on depression and lower scores in psychological flexibility/acceptance and self-compassion than the control group. This pattern was particularly identified in women who also tended to use less an emotional/detached coping style and to perceive themselves as less confident to deal with infertility than men. Multiple regression analysis showed that psychological flexibility/acceptance was a significant predictor of depressive symptoms in men and women with infertility. Emotional regulation processes, such as psychological flexibility/acceptance and self-compassion, seem to be relevant to the understanding of depressive symptoms and psychological adjustment to infertility, suggesting that these issues should be addressed in a therapeutic context with these couples. PMID- 22309793 TI - Interaction of transient receptor potential vanilloid 4 with annexin A2 and tubulin beta 5. AB - The aim of the present study was to investigate if there exists an interaction of TRPV4 with annexin A2 and with tubulin beta 5 in transfected human embryonic kidney (HEK293) cells in vitro. Coimmunoprecipitation of the rat dorsal root ganglion was performed to validly conform the interaction of TRPV4 with the other two proteins. Gene fragments coding for the amino acids in protein were obtained. We conducted coimmunoprecipitation and immunofluorescence on the transfected cell samples. Coimmunoprecipitation experiments of transfected HEK293 cells revealed that TRPV4 and tubulin beta 5 associated together in a complex, whereas TRPV4 and annexin A2 did not. The immunofluorescence microscopy revealed a colocalization of TRPV4 with both the tubulin beta 5 and annexin A2. These results indicate an interaction between TRPV4 and tubulin beta 5 by associating together. However, the association between TRPV4 and annexin A2 may be mediated by some intermediate elements or just exists in some physiological conditions. Thus, TRPV4 channel function may be modulated by tubulin beta 5 and annexin A2 and their interactions may play a role in the mechanosensation in the pathogenesis of neuropathic pain. PMID- 22309794 TI - Opposing roles of glucocorticoid receptor and mineralocorticoid receptor in trimethyltin-induced cytotoxicity in the mouse hippocampus. AB - The organotin trimethyltin (TMT) is known to cause neuronal degeneration in the murine brain. Earlier studies indicate that TMT-induced neuronal degeneration is enhanced by adrenalectomy and prevented by exogenous glucocorticoid. The aim of this study was to investigate the regulation of TMT neuroxicity by corticosterone receptors including type I (mineralocorticoid receptor, MR) and type II (glucocorticoid receptor, GR) in adult mice. The systemic injection of TMT at the dose of 2.0 or 2.8 mg/kg produced a marked elevation in the level of plasma corticosterone that was both dose and time dependent. The MR agonist aldosterone had the ability to exacerbate TMT cytotoxicity in the dentate granule cell layer, whereas its antagonist spironolactone protected neurons from TMT cytotoxicity there. In contrast, the GR antagonist mifepristone exacerbated the TMT cytotoxicity. Taken together, our data suggest TMT cytotoxicity is oppositely regulated by GR and MR signals, being exacerbated by MR activation in adult mice. PMID- 22309795 TI - Castrating parasites and colonial hosts. AB - Trajectories of life-history traits such as growth and reproduction generally level off with age and increasing size. However, colonial animals may exhibit indefinite, exponential growth via modular iteration thus providing a long-lived host source for parasite exploitation. In addition, modular iteration entails a lack of germ line sequestration. Castration of such hosts by parasites may therefore be impermanent or precluded, unlike the general case for unitary animal hosts. Despite these intriguing correlates of coloniality, patterns of colonial host exploitation have not been well studied. We examined these patterns by characterizing the responses of a myxozoan endoparasite, Tetracapsuloides bryosalmonae, and its colonial bryozoan host, Fredericella sultana, to 3 different resource levels. We show that (1) the development of infectious stages nearly always castrates colonies regardless of host condition, (2) castration reduces partial mortality and (3) development of transmission stages is resource mediated. Unlike familiar castrator-host systems, this system appears to be characterized by periodic rather than permanent castration. Periodic castration may be permitted by 2 key life history traits: developmental cycling of the parasite between quiescent (covert infections) and virulent infectious stages (overt infections) and the absence of germ line sequestration which allows host reproduction in between bouts of castration. PMID- 22309796 TI - Developing community-based preventive interventions in Hong Kong: a description of the first phase of the family project. AB - BACKGROUND: This paper describes the development of culturally-appropriate family based interventions and their relevant measures, to promote family health, happiness and harmony in Hong Kong. Programs were developed in the community, using a collaborative approach with community partners. The development process, challenges, and the lessons learned are described. This experience may be of interest to the scientific community as there is little information currently available about community-based development of brief interventions with local validity in cultures outside the West. METHODS: The academic-community collaborative team each brought strengths to the development process and determined the targets for intervention (parent-child relationships). Information from expert advisors and stakeholder discussion groups was collected and utilized to define the sources of stress in parent-child relationships. RESULTS: Themes emerged from the literature and discussion groups that guided the content of the intervention. Projects emphasized features that were appropriate for this cultural group and promoted potential for sustainability, so that the programs might eventually be implemented at a population-wide level. Challenges included ensuring local direction, relevance and acceptability for the intervention content, engaging participants and enhancing motivation to make behavior changes after a brief program, measurement of behavior changes, and developing an equal partner relationship between academic and community staff. CONCLUSIONS: This work has public health significance because of the global importance of parent-child relationships as a risk-factor for many outcomes in adulthood, the need to develop interventions with strong evidence of effectiveness to populations outside the West, the potential application of our interventions to universal populations, and characteristics of the interventions that promote dissemination, including minimal additional costs for delivery by community agencies, and high acceptability to participants. PMID- 22309797 TI - Patient and physician asthma deterioration terminology: results from the 2009 Asthma Insight and Management survey. AB - Long-term achievement of asthma control is dependent in part on the use of mutually understandable asthma terminology in all verbal and written patient physician communications. Using data from the Asthma Insight and Management (AIM) survey, the objective of this analysis is to provide a contemporary depiction of asthma deterioration terminology as used by current asthma patients and physicians in the United States. As part of the 2009 AIM survey, current asthma patients (>=12 years of age; weighted n = 2499) and physicians (n = 309) were queried about their recognition, understanding, and/or use of the terms "asthma attack," "asthma flare-up," and "asthma exacerbation" in telephone interviews. Nearly all patients had heard the term "asthma attack" (97%), but relatively few had heard the term "asthma exacerbation" (24%); 71% had heard "asthma flare-up." In contrast, physicians reported using the term "asthma attack" least (65%) and the term "asthma exacerbation" most (77%) when discussing asthma with their patients; 70% reported using "asthma flare-up." Among patients familiar with "asthma flare-up" and "asthma exacerbation" (n = 502), only 38% said that the terms mean the same thing; nearly all physicians (94%) said that the terms mean the same thing. Collectively, data from the AIM survey suggest that patients and physicians use different asthma deterioration terminology and, more importantly, that they do not necessarily understand each other's terms. Standardizing asthma deterioration terminology may help optimize asthma patient-physician communication to improve patient understanding of written asthma action plans and therefore, enhance patient outcomes. PMID- 22309798 TI - Genetic conservation of potentially immunogenic proteins among Brazilian isolates of Babesia bovis. AB - Bovine babesiosis caused by Babesia bovis remains an important constraint for the development of cattle industries worldwide. Effective control can be achieved by vaccination with live attenuated phenotypes of the parasite. However, these vaccines have a number of drawbacks, which justifies the search for better, safer vaccines. In recent years, a number of parasite proteins with immunogenic potential have been discovered. However, there is little information on the genetic conservation of these proteins among different parasite isolates, which hinders their assessment as immunogens. The aim of the present study was to evaluate the conservation of the genes ama-1, acs-1, rap-1, trap, p0 and msa2c among five Brazilian isolates of B. bovis. Through polymerase chain reaction, genetic sequencing and bioinformatics analysis of the genes, a high degree of conservation (98-100%) was found among Brazilian isolates of B. bovis and the T2Bo isolate. Thus, these genes are worth considering as viable candidates to be included in a recombinant cocktail vaccine for cattle babesiosis caused by B. bovis. PMID- 22309799 TI - Clinical evaluation of therapeutic success in rabbits with suspected encephalitozoonosis. AB - Between 2000 and 2008, 95 rabbits with suspected encephalitozoonosis and neurological symptoms were treated at the Clinic of Small Animal Medicine, Ludwig Maximilian University Munich. Standard treatment consisted of oxytetracycline (from 2000 to 2003; n=50) or fenbendazole and oxytetracycline (from 2004 to 2008; n=45), and the rabbits were randomly assigned to treatment groups with or without dexamethasone. Each therapeutic regime was given for 10 days, with fluids, B vitamins and nutritional support added as needed. Therapeutic success was evaluated by assessing the survival rate on day 10, the neurological score of the surviving rabbits and Kaplan-Meier curves for long-term survival past 10 days. Inclusion of fenbendazole in the treatment protocol was associated with increased survival rates on day 10 (p=0.043), better neurological scores (p=0.008), and improved long-term survival (p=0.025) based on the results of univariate analyses. Treatment with dexamethasone showed no effect on neurological score or on short- or long-term survival. The study did not provide any evidence that dexamethasone is an effective component of the treatment scheme. PMID- 22309800 TI - A longitudinal study of Neospora caninum infection on three dairy farms in Brazil. AB - Neospora caninum is an apicomplexan protozoan parasite that is one of the most important infectious causes of abortion in both dairy and beef cattle in many countries. The objectives of this longitudinal study were to determine the prevalence, rates of vertical and horizontal transmission of N. caninum and hazard for culling of N. caninum-seropositive animals in three Brazilian dairy herds. Blood samples from all animals were collected nine times at each of the three farms over a two-year period. Serum was tested for antibodies against N. caninum using the indirect fluorescent antibody test with a cutoff value of 1:100. The percentage of N. caninum-positive samples at each sampling time ranged at Farm I from 3.32% to 11.71%, at Farm II from 3.90% to 22.06% and at Farm III from 3.90% to 22.06%. The number of positive serological reactions varied in relation to the number of repeated samples taken from individual animals at each farm. In all herds, there was a high degree (P<0.05) of association between the N. caninum serological status of dams and daughters. The seropositive conversion rate was estimated as 0.37%, 3.00% and 6.94% per 100 cow-years at Farms I, II and III, respectively. The seronegative conversion rate was estimated as 31.58% and 11.11% per 100 cow-years at Farms I and III, respectively. In all herds, there was no difference (P>0.05) in the culling rate between the cattle that were seropositive cattle and seronegative for N. caninum infection. The results from this study confirm the importance of vertical transmission in the epidemiology of N. caninum. Although a few positive seroconversions indicated horizontal transmission, it does not appear to be the major route of infection for N. caninum. PMID- 22309801 TI - The relationship between polycystic ovary syndrome, glucose tolerance status and serum preptin level. AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is linked to obesity, impaired glucose tolerance and diabetes. Recently, studies have found that preptin enhances insulin secretion in rats and might play a role in the pathogenesis of diabetes and PCOS in humans. The aim of this study was to evaluate the relationship between PCOS, glucose tolerance status, and serum preptin level. METHODS: This study was conducted in a university-affiliated hospital from October 2010 to August 2011. Anthropometric parameters, sex hormone concentrations, blood pressure, lipid profiles, fasting glucose and insulin, 2-h blood glucose after glucose overloaded (2hOGTT), glycosylated haemoglobin (HbA1c), homeostasis model assessment-insulin resistance index (HOMA-IR), and serum preptin of the samples were analyzed. RESULTS: Sixty-three PCOS patients, including 33 women with normal glucose tolerance (NGT) and 30 women with impaired glucose tolerance (IGT), and 63 patients without PCOS, including 35 women with NGT and 28 women with IGT were recruited in this study. For patients with and without PCOS, women with IGT had higher serum preptin levels compared with women with NGT. Preptin levels in PCOS patients were higher compared with patients without PCOS, but the difference was not significant. Fasting serum preptin levels correlated positively with TG, SBP, DBP, FBG, 2hOGTT, and HOMA-IR in simple regression analysis of the pooled data. While in multiple stepwise regression analysis, preptin levels were independently related with glucose tolerance, but not with PCOS. CONCLUSIONS: Irrespective of PCOS status, women with IGT had higher serum preptin levels compared with women with NGT. Preptin levels are related with glucose tolerance status, but not with PCOS status. PMID- 22309802 TI - Finding the BOLD effect in brain images. AB - A brief description of events that led to the finding of BOLD effect in brain images is presented. This is a recollection of what were in this author's mind in pre-1992 period. PMID- 22309803 TI - A geographical history of social cognitive neuroscience. AB - The history of social cognitive neuroscience (SCN) began with isolated islands of research in Europe and the United States in the 1990s. In the decade between 1995 and 2004 most of the major areas of current SCN research were identified in a series of high profile first studies. This paper reviews the timeline as well as the geography of important moments in the short history of this field. Of note is the different focus seen in European contributions (theory of mind, mirror neurons, and empathy) and the more self-focused U.S. contributions (self knowledge, emotion regulation, implicit attitudes). PMID- 22309804 TI - Muscle protein metabolism in neonatal alloxan-administered rats: effects of continuous and intermittent swimming training. AB - BACKGROUND: This study aimed to examine the effects of intermittent and continuous swimming training on muscle protein metabolism in neonatal alloxan administered rats. METHODS: Wistar rats were used and divided into six groups: sedentary alloxan (SA), sedentary control (SC), continuous trained alloxan (CA), intermittent trained alloxan (IA), continuous trained control (CC) and intermittent trained control (IC). Alloxan (250 mg/kg body weight) was injected into newborn rats at 6 days of age. The continuous training protocol consisted of 12 weeks of swimming training in individual cylinder tanks while supporting a load that was 5% of body weight; uninterrupted swimming for 1 h/day, five days a week. The intermittent training protocol consisted of 12 weeks of swimming training in individual cylinder tanks while supporting a load that was 15% of body weight; 30 s of activity interrupted by 30 s of rest for a total of 20 min/day, five days a week. RESULTS: At 28 days, the alloxan animals displayed higher glycemia after glucose overload than the control animals. No differences in insulinemia among the groups were detected. At 120 days, no differences in serum albumin and total protein among the groups were observed. Compared to the other groups, DNA concentrations were higher in the alloxan animals that were subjected to continuous training, whereas the DNA/protein ratio was higher in the alloxan animals that were subjected to intermittent training. CONCLUSION: It was concluded that continuous and intermittent training sessions were effective in altering muscle growth by hyperplasia and hypertrophy, respectively, in alloxan administered animals. PMID- 22309805 TI - Effects of increased white blood cell count on endothelin-induced vasoconstriction in healthy subjects. AB - It is known that administration of granulocyte-colony stimulating factor is followed by an increase of white blood cell count. There is evidence from other vascular beds that an increase in white blood cell count impairs blood flow regulation especially in the microcirculation. Whether this also holds true for the ocular circulation is unknown. In the following study we investigated whether an increase in white blood cell count alters the endothelin-1 induced vasoconstriction in humans. Neither granulocyte-colony stimulating factor nor endothelin-1 had any consistent effect on blood pressure, pulse rate or intraocular pressure. Administration of granulocyte-colony stimulating factor induced a pronounced increase in retinal white blood cell density (p < 0.01). Administration of endothelin-1 decreased choroidal (p < 0.01) and retinal blood flow (p < 0.01). The change in choroidal blood flow in response to endothelin-1 was not altered by pre-treatment with granulocyte-colony stimulating factor. By contrast, the decrease in retinal blood flow was more pronounced during an increase in white blood cell count (p = 0.02) when compared to placebo. Our data indicates that during pronounced vasoconstriction, as induced by administration of endothelin-1, vascular regulation can be altered by the number of circulating white blood cells. Whether this effect is caused by an interaction of red and white blood cells in the microcirculation or a yet unknown mechanism needs further investigation. PMID- 22309806 TI - A national survey of the availability of intensity-modulated radiation therapy and stereotactic radiosurgery in Canada. AB - BACKGROUND: The timely and appropriate adoption of new radiation therapy (RT) technologies is a challenge both in terms of providing of optimal patient care and managing health care resources. Relatively little is known regarding the rate at which new RT technologies are adopted in different jurisdictions, and the barriers to implementation of these technologies. METHODS: Surveys were sent to all radiation oncology department heads in Canada regarding the availability of RT equipment from 2006 to 2010. Data were collected concerning the availability and use of Intensity Modulated Radiation Therapy (IMRT) and stereotactic radiosurgery (SRS), and the obstacles to implementation of these technologies. RESULTS: IMRT was available in 37% of responding centers in 2006, increasing to 87% in 2010. In 2010, 72% of centers reported that IMRT was available for all patients who might benefit, and 37% indicated that they used IMRT for "virtually all" head and neck patients. SRS availability increased from 26% in 2006 to 42.5% in 2010. Eighty-two percent of centers reported that patients had access to SRS either directly or by referral. The main barriers for IMRT implementation included the need to train or hire treatment planning staff, whereas barriers to SRS implementation mostly included the need to purchase and/or upgrade existing planning software and equipment. CONCLUSIONS: The survey showed a growing adoption of IMRT and SRS in Canada, although the latter was available in less than half of responding centers. Barriers to implementation differed for IMRT compared to SRS. Enhancing human resources is an important consideration in the implementation of new RT technologies, due to the multidisciplinary nature of the planning and treatment process. PMID- 22309807 TI - Intrinsic excitability is altered by hypothyroidism in the developing hippocampal CA1 pyramidal cells. AB - Thyroid hormone plays an essential role in brain development, so its deficiency during a critical developmental period has been associated with profound neurological deficits, including irreversible mental retardation. Despite the importance of the disorder, the cellular mechanisms underlying these deficits remain largely unexplored. The aim of this study was to examine the effects of the absence of thyroid hormone on the postnatal development of membrane excitability of CA1 hippocampal pyramidal cells. Current clamp recordings in the whole cell patch clamp configuration showed that the action potential of cells from hypothyroid animals presented shorter width, slower depolarization, and faster repolarization rates compared with controls both in early postnatal and pre-weanling ages. Additionally, thyroid hormone deficiency reduced the intrinsic membrane excitability as measured by the reduced number of evoked action potentials for a given depolarizing slope and by the more depolarized firing threshold observed in hypothyroid animals. Then we analyzed the fast-repolarizing A- and D-type potassium currents, as they constitute one of the major factors underlying intrinsic membrane excitability. Hypothyroid rats showed increased A current density and a reduced isolated I(D)-like current, accompanied by parallel changes in the expression of the channels responsible for these currents in the CA1 region: Kv4.2, Kv4.3, and Kv1.2. Therefore, we suggest that the increased A current density, subsequent to an increment in its channel expression, together with the decrease of Na(+)-currents, might help explain the functional alterations in the neuronal discharge, in the firing threshold, and in the action potential repolarization of hypothyroid pyramidal neurons. PMID- 22309808 TI - The influence of the dynamic transformation of a sliding lever on aiming errors. AB - Human movements are quickly adjusted to variations of inertial load. However, this adjustment does not always imply a full compensation, so that kinematic movement characteristics vary. The present experiment served to explore the consequences of a complex dynamic transformation, implemented by a sliding first order lever, on the endpoint distributions of goal-directed movements. Whereas the endpoint distributions were clearly affected by the inertial anisotropy of the arm, there was no effect of the dynamic transformation of the lever, neither on the parameters of endpoint distributions nor on the covariations of endpoints of successive movements (error propagation). However, when the lever was used, the effect of the inertial anisotropy of the arm on movement amplitudes was reduced, accompanied by a longer movement time overall, in particular for movements with higher inertial load of the arm. These observations suggest an interaction of the use of internal models and impedance control in the presence of variable inertial loads. Most likely the influence of the dynamic transformation of the sliding lever is absorbed by increased joint impedance, which also reduces the influence of the inertial anisotropy of the arm which otherwise is (incompletely) compensated based on an internal model of the dynamic transformation of the arm. PMID- 22309809 TI - Design of a framework for modeling, integration and simulation of physiological models. AB - Multiscale modeling and integration of physiological models carry challenges due to the complex nature of physiological processes. High coupling within and among scales present a significant challenge in constructing and integrating multiscale physiological models. In order to deal with such challenges in a systematic way, there is a significant need for an information technology framework together with related analytical and computational tools that will facilitate integration of models and simulations of complex biological systems. Physiological Model Simulation, Integration and Modeling Framework (Phy-SIM) is an information technology framework providing the tools to facilitate development, integration and simulation of integrated models of human physiology. Phy-SIM brings software level solutions to the challenges raised by the complex nature of physiological systems. The aim of Phy-SIM, and this paper is to lay some foundation with the new approaches such as information flow and modular representation of the physiological models. The ultimate goal is to enhance the development of both the models and the integration approaches of multiscale physiological processes and thus this paper focuses on the design approaches that would achieve such a goal. PMID- 22309810 TI - Uptake and release of paralytic shellfish toxins by the clam Ruditapes decussatus exposed to Gymnodinium catenatum and subsequent depuration. AB - A laboratory experiment was performed with the clam Ruditapes decussatus, fed with the toxic dinoflagellate Gymnodinium catenatum and the non-toxic algae Isochrysis galbana (14 days) and subsequently only with I. galbana (15 days). Individual paralytic shellfish toxins were determined by LC-FLD in G. catenatum cells, whole clam tissues, and particulate organic matter (POM) produced by clams. The toxins dcSTX and dcGTX2 + 3 in the algae were less abundant than C1 + 2 and B1, but were predominant in clams during both the exposure and depuration phases. The toxin dcNEO was only detected in clams during a short period, indicating conversion from other compounds. The toxin composition of the POM indicated the export of dcSTX as faeces or pseudo-faeces along the entire experiment (2.5-14 nmol mg(-1)), B1 was present in a short period of the exposure and C1 + 2 and dcGTX2 + 3 absent. A mass balance calculation indicated that approximately 95% of C1 + 2 and 85% of B1 supplied to the clams were converted into other toxins or lost in solution. Conversely, the net gain of 512, 61 and 31 nmol for dcSTX, dcGTX2 + 3 and dcNEO, respectively, suggests the conversion from other assimilated compounds by clams during exposure and depuration phases. PMID- 22309811 TI - The toxin component of targeted anti-tumor toxins determines their efficacy increase by saponins. AB - Tumor-targeting protein toxins are composed of a toxic enzyme coupled to a specific cell binding domain that targets cancer-associated antigens. The anti tumor treatment by targeted toxins is accompanied by dose-limiting side effects. The future prospects of targeted toxins for therapeutic use in humans will be determined by reduce side effects. Certain plant secondary metabolites (saponins) were shown to increase the efficacy of a particular epidermal growth factor receptor (EGFR)-targeted toxin, paralleled by a tremendous decrease of side effects. This study was conducted in order to investigate the effects of substituting different toxin moieties fused to an EGF ligand binding domain on the augmentative ability of saponins for each against therapeutic potential of the saponin-mediated efficacy increase for different anti-tumor toxins targeting the EGFR. We designed several EGFR-targeted toxins varying in the toxic moiety. Each targeted toxin was used in combination with a purified saponin (SA1641), isolated from the ornamental plant Gypsophila paniculata L. SA1641 was characterized and the SA1641-mediated efficacy increase was investigated on EGFR transfected NIH-3T3 cells. We observed a high dependency of the SA1641-mediated efficacy increase on the nature of toxin used for the construction of the targeted toxin, indicating high specificity. Structural alignments revealed a high homology between saporin and dianthin-30, the two toxic moieties that benefit most from the combination with SA1641. We further demonstrate that SA1641 did not influence the plasma membrane permeability, indicating an intracellular interaction of SA1641 and the toxin components of targeted toxins. Surface plasmon resonance measurements point to a transient binding of SA1641 to the toxin components of targeted toxins. PMID- 22309812 TI - Systemic air embolism during percutaneous core needle biopsy of the lung: frequency and risk factors. AB - BACKGROUND: Detection of risk factors for an air embolism in the left atrium, left ventricle, or systemic circulation (systemic air embolism, SAE) during a percutaneous core needle biopsy (PCNB) of the thorax. METHODS: In a retrospective observational study, all PCNBs of the thorax in 610 patients between 2007 and 2009 were analyzed. The SmartStepTM technique (General Electric) was used for the biopsy, with which the examiner can prepare a batch of three 1.25-mm or 2.5-mm collimated slices within a second using a foot switch in the CT room to check the needle position. The image data thus generated and the control CT scans that followed were examined retrospectively for the presence of intravascular air. Intravascular air was defined as two or more adjacent voxels with absorption values of < -200 HU in the left atrium, left ventricle, aorta, or arteries during or after the procedure. The univariate statistical analysis of categorical variables was made using 2 by 2 tables and the Fisher test. The groups were compared using the Mann-Whitney test. Finally, a multivariate logistic regression analysis was used to identify independent risk factors for the occurrence of an SAE. RESULTS: The radiological incidence of an SAE during a PCNB was 3.8% (23/610 patients), whereas the clinically apparent incidence was 0.49%. Two patients developed clinical symptoms consisting of transient hemiplegia or transient amaurosis; one died due to a fatal SAE of the coronary arteries. The mortality was thus 0.16%. The depth of the needle in the lesion (Wald: 6.859), endotracheal anesthesia (Wald: 5.721), location of the lesion above the level of the left atrium (Wald: 5.159), and prone position of the patients (Wald: 4.317) were independent risk factors for the incidence of an SAE (p < 0.05 each). Using explorative criteria, the acute angle of the needle to the tumor surface, and the transition of ventilated lung were independent factors. The frequency of biopsies, needle penetration depth, and tumor location near the diaphragm or in the lower lobe also played a subordinate role, not however, the needle penetration depth through the lung. CONCLUSION: If possible, the PCNB should be performed under local anesthesia. We recommend avoiding endotracheal anesthesia and prone position. Whenever possible, patients should be positioned on the back in such a way that the tumor is lower than the left atrium. The tip of the needle should be within the tumor during the biopsy procedure. PMID- 22309813 TI - Test context affects recollection and familiarity ratings: implications for measuring recognition experiences. AB - The binary remember/know task requires participants to dichotomize their subjective recognition experiences into those with recollection and those only with familiarity. Many variables have produced dissociative effects on remember/know judgments. In contrast, having participants make independent recollection/familiarity ratings has consistently produced parallel effects, suggesting the dissociations may be artifacts of using binary judgments. Bodner and Lindsay (2003) reported a test-list context effect with binary judgments: Increased remembering but decreased knowing for a set of critical items tested with a set of less-memorable (vs. more-memorable) items. Here we report a parallel effect of test-list context on recollection and familiarity ratings, induced by a shift in response bias. We argue that independent ratings are preferable to binary judgments because they allow participants to directly report the co-occurrence of recollection and familiarity for each item. Implications for the measurement of self-reported recognition experiences, and for accounts of recognition memory, are discussed. PMID- 22309814 TI - Mindfulness meditation counteracts self-control depletion. AB - Mindfulness meditation describes a set of different mental techniques to train attention and awareness. Trait mindfulness and extended mindfulness interventions can benefit self-control. The present study investigated the short-term consequences of mindfulness meditation under conditions of limited self-control resources. Specifically, we hypothesized that a brief period of mindfulness meditation would counteract the deleterious effect that the exertion of self control has on subsequent self-control performance. Participants who had been depleted of self-control resources by an emotion suppression task showed decrements in self-control performance as compared to participants who had not suppressed emotions. However, participants who had meditated after emotion suppression performed equally well on the subsequent self-control task as participants who had not exerted self-control previously. This finding suggests that a brief period of mindfulness meditation may serve as a quick and efficient strategy to foster self-control under conditions of low resources. PMID- 22309815 TI - Modelling the transmission dynamics of Theileria annulata: model structure and validation for the Turkish context. AB - A mathematical model that describes the transmission dynamics of Theileria annulata is proposed that consists of 2 host components: the Hyalomma tick population and a compartmental model of T. annulata infection in the cattle population. The model was parameterized using data describing tick infestation and the infection status of cattle in Turkey from 2006 to 2008. The tick attachment rates are highly seasonal and because of the temporal separation of infectious and susceptible ticks virtually all ticks are infected by carrier cattle, so that annual peaks of disease in cattle do not impact on infection in the Hyalomma tick population. The impact of intervention measures that target the tick population both on the host and in the environment and their impact on the transmission of T. annulata were investigated. Interventions that have a limited 'one-off' impact and interventions that have a more permanent impact were both considered. The results from the model show the importance of targeting ticks during the period when they have left their first host as nymphs but have yet to feed on their second host. PMID- 22309816 TI - The relationship between posttraumatic stress disorder symptoms and paternal parenting of adult children among ex-prisoners of war: a longitudinal study. AB - The aversive impact of combat and combat-induced posttraumatic stress disorder (PTSD) on parenting of young children has been examined in a few studies. Nevertheless, the toll of war captivity on parenting and the long-term relations between posttraumatic symptoms and paternal parenting of adult children remains unknown. This longitudinal study examined paternal parenting of adult children among war veterans, some of whom were held in captivity. Furthermore, we examined the mediating role of PTSD symptoms in the association between captivity and parenting. The sample included two groups of male Israeli veterans from the 1973 Yom Kippur War: ex-prisoners of war (ex-POWs) and comparable veterans who had not been held captive. Both groups were assessed via self-report measures of PTSD at three time points: Time 1 (18 after the war), Time 2 (30 after the war), and Time 3 (35 after the war) years after the war. Results shows that ex-POWs reported lower levels of positive parenting compared to comparison group veterans at Time 3. Furthermore, PTSD symptoms at Time 1, Time 2, and Time 3 mediated the association between captivity experience and parenting at Time 3. In addition, it was found that increases in the levels of PTSD symptom clusters over time were associated with lower levels of positive parenting at Time 3. PMID- 22309817 TI - Item response theory analysis of intimate-partner violence in a community sample. AB - The Revised Conflict Tactics Scale (CTS2; Straus, Hamby, Boney-McCoy, & Sugarman, 1996) is a widely used measure of physical, psychological, and sexual aggression as well as injury and negotiation between partners. In this study, we analyzed male-to-female and female-to-male physical aggression using data from 453 community couples. We used item-response theory (IRT) to assess the range and precision of physical aggression severity in the past year, as evaluated by the CTS2. Our analyses support a single dimension of physical aggression with quantitative, rather than qualitative, differentiation between minor and severe physical aggression items. Surprisingly, test information curves revealed that male perpetration and victimization items provided as much or more information as their counterpart female victimization and perpetration items over the same range of aggression severity. Finally, the data suggests that CTS2 items best assessed moderate-to-severe levels of physical aggression in the previous 12 months. However, virtually no information was assessed by male or female reports of perpetration or victimization items below or around the mean of aggression (i.e., theta; theta = 0). Suggestions for improved item coverage and implications for the assessment of aggression are discussed. PMID- 22309818 TI - Understanding treatment effectiveness for aggressive youth: the importance of regulation in mother-child interactions. AB - Reviews summarizing hundreds of studies cite parent management training (PMT) and cognitive-behavior therapy (CBT) as some of the most effective interventions for aggressive youth. However, studies continue to report variability in outcomes, and researchers have yet to understand why certain interventions only produce behavior change in some children. Using a clinical sample of 57 children (53 boys, 4 girls; mean age = 9.33, standard deviation = 1.16) and their mothers enrolled in a combined PMT/CBT program, the current study examined the relation between changes in real-time mother-child interactions, and children's externalizing outcomes from pre- to posttreatment. Results showed that dyads who were regulated in their interactions over time reported greater reductions in externalizing symptoms from pre- to posttreatment as compared with dysregulated dyads. Changes in mean levels of affective content (e.g., negativity) were not associated with externalizing outcomes. Findings suggest that dyadic regulation may be an important process associated with treatment success for aggressive youth. PMID- 22309819 TI - A randomized clinical trial of online-biblio relationship education for expectant couples. AB - This study evaluated the efficacy of a self-paced, Internet-based marriage and relationship skills education program ("Power of Two Online"). The program integrated an online intervention with print supplemental resources. New and expectant parents (n = 79) were randomly assigned to the 2-month intervention or placebo-control group. Assessments were conducted at baseline, 1-month, and 2 month follow-up intervals. Latent growth curve modeling was used to examine differences between conditions for marital satisfaction and conflict management. Participants who received the intervention reported trajectories of improved marital satisfaction and improved marital conflict management over time relative to controls. Implications for widespread dissemination of marriage and relationship education as a primary prevention tool are discussed. PMID- 22309820 TI - Examining changes in relationship adjustment and life satisfaction in marriage. AB - The current study examined the association between relationship adjustment and life satisfaction before marriage to 6 years into marriage in a sample of 126 couples. Results showed that both premarital relationship adjustment and premarital life satisfaction uniquely predicted marital adjustment 6 years into marriage. Premarital life satisfaction, but not premarital relationship adjustment, predicted life satisfaction 6 years into marriage. While premarital relationship adjustment scores were not uniquely associated with future life satisfaction scores, changes in relationship adjustment were positively associated with future life satisfaction. These findings are supportive of the idea that helping people to improve their relationships may increase overall life satisfaction. The findings also suggest that, while an individual's base level of life satisfaction may set some parameters for the course of relationship adjustment, changes in life satisfaction over time impact marital adjustment. Starting marriage with higher life satisfaction may increase chances for a happier marriage. Overall, the findings suggest that life satisfaction plays a role in marital adjustment over time, and that it is important to consider life satisfaction as not only an outcome associated with relationship adjustment but also as a predictor of relationship adjustment. PMID- 22309821 TI - The salivary gland epithelial cells of patients with primary Sjogren's syndrome manifest significantly reduced responsiveness to 17beta-estradiol. AB - Several lines of evidence indicate that salivary gland epithelial cells (SGEC) play an important role in the pathogenesis of primary Sjogren's syndrome (SS). Normal SGEC have been shown to possess functional estrogen receptors, however, the estrogenic response of SGEC in patients with SS has not been previously assessed. To address this issue, we comparatively tested cultured non-neoplastic SGEC lines from SS patients (SS-SGEC, n = 8) and from disease controls (control SGEC, n = 12) in a standard estrogenic inhibition assay of cytokine-induced adhesion molecule expression, where the modulation of the expression of constitutive and interferon-gamma (IFNgamma)-induced CD54/ICAM.1 molecules following treatment with 17beta-estradiol (E2) was evaluated by flow cytometry. Similarly high ICAM.1 expression was induced by IFNgamma in control-SGEC and SS SGEC lines. E2-treatment did not modify the constitutive ICAM.1 expression in either control-SGEC or SS-SGEC lines. In line with previous results, E2 pretreatment of control-SGEC was found to impede significantly the IFNgamma induced upregulation of ICAM.1 (p = 0.003). However, such inhibition was not observed in the SS-SGEC lines (p = 0.55). Such aberrant response of SS-SGEC to estrogens did not appear to associate with altered expression of estrogen receptor (ER) proteins, as no discernible differences could be revealed by immunoblotting and immunohistochemistry in the patterns or the intensity of ERalpha and ERbeta (ERbeta1- and ERbeta2-isoforms) protein expression in SGEC lines or minor salivary gland tissues between SS patients and disease controls. The deficient estrogenic responsiveness of SS-SGEC likely represents a manifestation of the intrinsic epithelial activation that characterizes SS and possibly indicates the perturbation of the immunoregulatory potential of estrogens in SS-epithelia. PMID- 22309822 TI - In vitro evidence for chronic alcohol and high glucose mediated increased oxidative stress and hepatotoxicity. AB - BACKGROUND: Hyperglycemia or alcoholism can lead to impaired liver functions. Cytochrome P450 2E1 (CYP2E1) is elevated in hyperglycemia or alcoholism and plays a critical role in generating oxidative stress in the cell. METHODS: In the present study, we have used VL-17A cells that overexpress the alcohol metabolizing enzymes [alcohol dehydrogenase (ADH) and CYP2E1] to investigate the toxicity due to ethanol (EtOH) plus high glucose. Toxicity was assessed through viability assay and amount of acetaldehyde adduct formation. Oxidative stress parameters included measuring reactive oxygen species (ROS) levels and malondialdehyde adduct formation. Apoptosis was determined through caspase-3 activity, Annexin V- Propidium iodide staining, and changes in mitochondrial membrane potential. The effects of antioxidants and specific inhibitors of ADH and CYP2E1 on cell viability and ROS levels were also studied. RESULTS: When present together, EtOH plus high glucose-treated VL-17A cells exhibited greater oxidative stress and toxicity than other groups. Apoptosis was observed in liver cells treated with the toxins, and the EtOH plus high glucose-treated VL-17A cells exhibited apoptosis to the largest extent. A distinct and graded increase in CYP2E1 level occurred in the different groups of VL-17A cells. Further, antioxidants or inhibitors of ADH and CYP2E1 were effective in decreasing the observed oxidative stress and toxicity. CONCLUSIONS: The combined oxidative insult due to alcohol plus high glucose leads to greater liver injury, which may prove to be a timely warning for the injurious effects of alcohol consumption in diabetics. PMID- 22309823 TI - Tele-assistance in patients with amyotrophic lateral sclerosis: long term activity and costs. AB - PURPOSE: To describe i) nurse's utilisation and associated costs during 4-year tele-assistance in amyotrophic lateral sclerosis (ALS) ii) optimal time for initiating tele-assistance. METHOD: 73 ALS patients after hospital discharge were followed up on voice by phone calls conducted by a nurse through a clinical card which was tested for feasibility, efficacy and utility. Number of patients simultaneously assisted/month, calls/patient, fixed and variable costs were calculated. RESULTS: Time between disease's diagnosis and the beginning of tele assistance was 720 +/- 971 days. ALS patients' percentage managed by nurses through tele-assistance increased over time by 628%. Tele-assistance integrated care (TAIC) followed up patients with a total of 5073 telephone calls. Steady state activity was reached at the 3rd year employing 5 +/- 3 calls/pt/month (time/call 64 +/- 44 min). Implementing the card was feasible, useful and effective by operator. Survival from diagnosis of ALS was 1224 +/- 1150 days. Survival was related to tracheotomy. CONCLUSION: TAIC is a feasible tool to manage up to 25 ALS patients/month/nurse and costs about ?105.00 per patient per month. Tele-assistance is proposed at 2/3 of time course of the disease. PMID- 22309824 TI - Positive life events predict salivary cortisol in pregnant women. AB - Maternal stress during pregnancy has been repeatedly associated with problematic child development. According to the fetal programming hypothesis adverse experiences during pregnancy increase maternal cortisol, which is then assumed to exert a negative effect on fetal development. Recent studies in non-pregnant women report significant associations between positive emotionality and low cortisol levels. We tested in a sample of 60 pregnant women whether both negative and positive life events independently predicted third-trimester baseline awakening cortisol levels. While the effect of negative life events proved unrelated positive life events significantly predicted lower cortisol levels. These findings suggest that positive experiences are of relevance regarding maternal morning cortisol levels in pregnancy reflecting a resource with potentially beneficial effects for the mother and the developing fetus. It might be promising for psychological intervention programs to focus on increasing positive experiences of the expecting mother rather than exclusively trying to reduce maternal stress during pregnancy. PMID- 22309825 TI - The relation between emotion regulation strategies and physiological stress responses in middle childhood. AB - The current study sought to examine whether children's spontaneous use of the emotion regulation strategies suppression and reappraisal during a psychosocial stress task was related to their cortisol and alpha-amylase responses to that task. Salivary cortisol and alpha-amylase responses to a psychosocial stress task were assessed in 158 10-year-old children (83 girls). The children completed a self-report questionnaire measuring use of reappraisal and suppression during the task. Results showed overall increases in cortisol and alpha-amylase in response to the stressor, with higher cortisol reactivity in girls than in boys. With regard to emotion regulation, more use of suppression was related to lower cortisol reactivity in girls, and lower alpha-amylase reactivity and quicker alpha-amylase recovery in all children. The use of reappraisal was not related to the children's cortisol or alpha-amylase responses. The current study is the first to investigate the relation between the spontaneous use of reappraisal and suppression, and physiological stress responses to a psychosocial stressor in children. Our results indicate that reappraisal and suppression are used and can be measured even in 10-year-olds. At this age reappraisal appears ineffective at down-regulating physiological responses, while suppression was related to lower physiological responses. For cortisol reactivity there was a sex difference in the relation with suppression, indicating the importance of including sex as a moderator variable in research studying stress reactivity and its correlates in this age group. PMID- 22309826 TI - Within and between session changes in subjective and neuroendocrine stress parameters during magnetic resonance imaging: A controlled scanner training study. AB - Accumulating evidence suggests that the magnetic resonance imaging (MRI) scanner can act as a stressor, eliciting subjective and neuroendocrine stress responses. Approaches to familiarize subjects with the scanner could help minimizing unintended effects on neural activation patterns of interest. Controlled studies on the effects of a scanner training are however missing. Using a comparative design, we analyzed within- and between session changes in subjective and neuroendocrine stress parameters in 63 healthy, scanner-naive adults who participated in a two-day training protocol in an MRI, mock, or lab environment. A habituation task was used to assess within-session changes in subjective and neuroendocrine (cortisol) stress parameters; between-session changes were indicated by differences between days. MRI and mock, but not lab training were successful in reducing subjective distress towards the scanner. In contrast, cortisol reactivity towards the training environment generally increased during day 2, and the percentage of cortisol responders particularly rose in the mock and MRI groups. Within-session habituation of subjective arousal and anxiety was observed during both days and irrespective of training condition. Present findings demonstrate that training in a scanner environment successfully reduces subjective distress, but may also induce sensitization of endocrine stress levels during repeated scanning. Subjective distress can further be stabilized by acclimating subjects to the environment prior to the MRI assessment, including a short habituation phase into the assessment protocol. If replicated, present findings should be considered by researchers employing repeated measurement designs where subjects are exposed to a scanner more than once. PMID- 22309827 TI - Estrogens and memory in physiological and neuropathological conditions. AB - Ovarian hormones can influence brain regions crucial to higher cognitive functions, such as learning and memory, acting at structural, cellular and functional levels, and modulating neurotransmitter systems. Among the main effects of estrogens, the protective role that they may play against the deterioration of cognitive functions occurring with normal aging is of essential importance. In fact, during the last century, there has been a 30 years increase in female life expectancy, from 50 to 83 years; however, the mean age of spontaneous menopause remains stable, 50-51 years, with variability related to race and ethnicity. Therefore, women are now spending a greater fraction of their lives in a hypoestrogenic state. Although many cognitive functions seem to be unaffected by normal aging, age-related impairments are particularly evident in tasks involving working memory (WM), whose deficits are a recognized feature of Alzheimer's disease (AD). Many studies conducted over the past two decades showed that the female gonadal hormone estradiol can influence performance of learning and memory tasks, both in animal and humans. There is a great deal of evidence, mostly from animal models, that estrogens can facilitate or enhance performance on WM tasks; therefore, it is very important to clarify their role on this type of memory. To this aim, in this review we briefly describe the most relevant neurobiological bases of estrogens, that can explain their effects on cognitive functioning, and then we summarize the results of works conducted in our laboratory, both on animals and humans, utilizing the menstrual/estrous cycle as a useful noninvasive model. Finally, we review the possible role of estrogens in neuropathological conditions, such as AD and schizophrenia. PMID- 22309828 TI - Comparison of the Asthma in America and Asthma Insight and Management surveys: did asthma burden and care improve in the United States between 1998 and 2009? AB - Significant changes in asthma treatment guidelines and therapies occurred between the period of time in which the Asthma in America (AIA) and Asthma Insight and Management (AIM) surveys were conducted: 1998 and 2009, respectively. This study compares asthma burden and management in 1998 and 2009. Both surveys were telephone based and conducted across the United States. The AIA survey included 2509 patients with asthma (aged <1 year to 89 years old), 512 physicians, and 1000 adults from the general population. The AIM survey included 2500 patients (aged >=12 years), 309 physicians, and 1090 adults from the general population. Patient responses were weighted to match the entire population of U.S. patients with asthma. The impact of asthma burden and care on the general population and on asthma patients was slightly lower or unchanged in the AIM survey versus the AIA survey. Acute care use (hospitalizations, emergency department visits, or other urgent care visits) was common in AIA (36%) and AIM (34%) surveys. Most physicians were aware of guidelines in AIA (90%) and AIM (96%), but fewer "always" followed them (AIA, 36%; AIM, 28%). Spirometry was often used to aid in diagnosis by asthma care specialists (AIA, 73%; AIM, 76%) but infrequently by nonsubspecialists (AIA, 27%; AIM, 38%). Most physicians prescribed inhaled corticosteroids (ICSs) for mild (AIA, 70%; AIM, 83%) or moderate (AIA, 89%; AIM, 83%) persistent asthma. In the AIM survey, 38% of specialists prescribed ICSs combined with a long-acting beta2-agonist for moderate asthma. The state of U.S. asthma care and clinical outcomes changed little from 1998 to 2009. PMID- 22309829 TI - Prostaglandin E2 contributes to the synthesis of brain-derived neurotrophic factor in primary sensory neuron in ganglion explant cultures and in a neuropathic pain model. AB - Brain-derived neurotrophic factor (BDNF) exists in small to medium size neurons in adult rat dorsal root ganglion (DRG) and serves as a modulator at the first synapse of the pain transmission pathway in the spinal dorsal horn. Peripheral nerve injury increases BDNF expression in DRG neurons, an event involved in the genesis of neuropathic pain. In the present study, we tested the hypothesis that prostaglandin E2 (PGE2) over-produced in injured nerves contributes to the up regulation of BDNF in DRG neurons. Two weeks after partial sciatic nerve ligation (PSNL), BDNF levels in the ipsilateral L4-L6 DRG of injured rats were significantly increased compared to the contralateral side. Perineural injection of a selective cyclooxygenase (COX2) inhibitor or a PGE2 EP4 receptor antagonist not only dose-dependently relieved PSNL elicited mechanical hypersensitivity, but also suppressed the increased BDNF levels in DRG neurons. PSNL shifted BDNF expression in the ipsilateral DRG from small to medium and larger size injured neurons. BDNF is mainly co-expressed with the EP1 and EP4 while moderately with the EP2 and EP3 receptor subtypes in naive and PSNL rats. PSNL also shifted the expression of EP1-4 receptors to a larger size population of DRG neurons. In DRG explant cultures, a stabilized PGE2 analog 16,16 dimethyl PGE2 (dmPGE2) or the agonists of EP1 and EP4 receptors significantly increased BDNF levels and the phosphorylated protein kinase A (PKA), extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) and cAMP response element binding protein (CREB). The EP1 and EP4 antagonists, a sequester of nerve growth factor (NGF), the inhibitors of PKA and MEK as well as CREB small interfering RNA suppressed dmPGE2-induced BDNF. Taken together, EP1 and EP4 receptor subtypes, PKA, ERK/MAPK and CREB signaling pathways as well as NGF are involved in PGE2 induced BDNF synthesis in DRG neurons. Injured nerve derived-PGE2 contributes to BDNF up-regulation in DRG neurons following nerve injury. Facilitating the synthesis of BDNF in primary sensory neurons is a novel mechanism underlying the role of PGE2 in the genesis of neuropathic pain. PMID- 22309830 TI - Changes in network dynamics during status epilepticus. AB - Status epilepticus (SE) is an acute event, characterized by repeated or continuous seizures, which alters neuronal properties of the brain and can promote the epileptic disorder. Experimental observations indicate that SE becomes progressively less responsive to anti-epileptic drugs, suggesting changes in the underlying physiology. To assess the effect of SE on neuronal dynamics as it progresses, we measured changes in neuronal activity from CA3 hippocampus, ipsilateral and contralateral to a focal intrahippocampal injection of kainic acid during the full course of SE, 24 h post-SE, and one week post-SE. The progressively intensifying behavioral response during SE was accompanied by changes in intrinsic firing properties of single neurons, LFP oscillations and interaction between single neurons and the oscillations. These results show important changes in neuronal and network activity underlying the progression of SE. PMID- 22309831 TI - Delayed caffeine treatment prevents nigral dopamine neuron loss in a progressive rat model of Parkinson's disease. AB - Parkinson's disease (PD) is characterized by a prominent degeneration of nigrostriatal dopamine (DA) neurons with an accompanying neuroinflammation. Despite clinical and preclinical studies of neuroprotective strategies for PD, there is no effective treatment for preventing or slowing the progression of neurodegeneration. The inverse correlation between caffeine consumption and risk of PD suggests that caffeine may exert neuroprotection. Whether caffeine is neuroprotective in a chronic progressive model of PD has not been evaluated nor is it known if delayed caffeine treatment can stop DA neuronal loss. We show that a chronic unilateral intra-cerebroventricular infusion of 1-methyl-4 phenylpyridinium in the rat brain for 28 days produces a progressive loss of DA and tyrosine hydroxylase in the ipsilateral striatum and a loss of DA cell bodies and microglial activation in the ipsilateral substantia nigra. Chronic caffeine consumption prevented the degeneration of DA cell bodies in the substantia nigra. Importantly, neuroprotection was still apparent when caffeine was introduced after the onset of the neurodegenerative process. These results add to the clinical relevance for adenosine receptors as a disease-modifying drug target for PD. PMID- 22309832 TI - Role of noncoding RNAs in trinucleotide repeat neurodegenerative disorders. AB - Increasingly complex networks of noncoding RNAs are being found to play important and diverse roles in the regulation of gene expression throughout the genome. Many lines of evidence are linking mutations and dysregulations of noncoding RNAs to a host of human diseases, and noncoding RNAs have been implicated in the molecular pathogenesis of some neurodegenerative disorders. The expansion of trinucleotide repeats is now recognized as a major cause of neurological disorders. Here we will review our current knowledge of the proposed mechanisms behind the involvement of noncoding RNAs in the molecular pathogenesis of neurodegenerative disorders, particularly the sequestration of specific RNA binding proteins, the regulation of antisense transcripts, and the role of the microRNA pathway in the context of known neurodegenerative disorders caused by the expansion of trinucleotide repeats. PMID- 22309833 TI - Effect of (S)-3,5-DHPG on microRNA expression in mouse brain. AB - MicroRNAs are small non-coding RNAs that regulate post-transcriptional gene expression. In the short time since the discovery of microRNAs, the literature has burgeoned with studies focused on the biosynthesis of microRNAs, target prediction and binding, and mechanisms of translational repression by microRNAs. Given the prominent role of microRNAs in all areas of cell biology, it is not surprising that microRNAs are also linked to human diseases, including those of the nervous system. One of the least-studied areas of microRNA research is how their expression is regulated outside of development and cancer. Thus, we examined a role for regulation of microRNAs by neurotransmitter receptor activation in mouse brain. We focused on the group I metabotropic glutamate receptors by using intracerebroventricular injection of the selective agonist, (S)-3,5-dihydroxyphenylglycine (DHPG) in mouse brain. We then examined the expression of microRNAs in the cerebral cortex by Ambion and Invitrogen microarrays, and the expression of mature microRNA sequences by SABiosciences qPCR arrays, at 4, 8 and 24 h after DHPG injection. These studies revealed that the largest number of significantly regulated microRNAs was detected 8h after DHPG injection in the microarrays and qPCR arrays. We then used RNA blots to quantify microRNA expression, and in situ hybridization to examine cellular distribution of the microRNAs regulated by DHPG. Bioinformatic analysis of the microRNAs regulated 8 h after DHPG in all three arrays revealed KEGG pathways that are known to correlate with group I mGluR effects, as well as recently described and novel pathways. These studies are the first to show that DHGP regulates the expression of microRNAs in mouse cerebral cortex, and support the hypothesis that group I mGluRs may regulate microRNA expression in mouse brain. PMID- 22309834 TI - Lactulose: an effective preventive and therapeutic option for ischemic stroke by production of hydrogen. AB - Lactulose, a synthetic sugar not able to be digested and absorbed by human beings, is widely used to treat constipation and hepatic encephalopathy clinically. Through fermentation by the bacteria in the gastrointestinal tract, lactulose can produce considerable amount of hydrogen, which is protective for ischemic stroke as a unique antioxidant. We propose that lactulose can induce the production of endogenous hydrogen that in turn reduces oxidative stress and ameliorate the stroke damage in human beings. PMID- 22309835 TI - Hyberbaric oxygen increases atresia in normal & steroid induced PCO rat ovaries. AB - BACKGROUND: In this study, we investigated the effect of hyperbaric oxygen therapy (HBOT) on the morphology of estradiol valerate (EV) induced polycystic ovary (PCO) to find a new treatment modality for improvement of PCO. METHODS: The rats were divided into four groups. Group1, control; group 2, PCO group; group 3, PCO with HBOT group and group 4, normal ovary with HBOT. PCO was induced by a single intramuscular injection of 4 mg EV in adult cycling rats. Other rats with normal ovaries had oil injection as placebo. HBOT was applied to third and fourth groups for six weeks. Histopathologic evaluation of ovaries of all groups were performed & compared. RESULTS: Six weeks of HBOT was resulted in increase in follicular atresia, decrease in the number of primary, secondary, tertiary follicles and decrease in the number of fresh corpus luteum in normal rat ovary. HBOT on polycystic rat ovary, resulted in significant increase in atretic follicles which were already present. CONCLUSIONS: HBOT of six weeks itself, changed ovarian morphology in favor of atresia both in PCO group and control group. This result of aggravated follicular atresia after HBOT on EV induced PCO may be due to long-term exposure in our protocol which with this state seems to be inapplicable in the improvement of PCO morphology. PMID- 22309836 TI - Hormone-responsive 3D multicellular culture model of human breast tissue. AB - A hormone-responsive 3D human tissue-like culture system was developed in which human primary mammary epithelial cells (MECs) were co-cultured with two types of predominant mammary stromal cells on silk protein scaffolds. Silk porous scaffolds with incorporated extracellular matrix provided a compatible environment for epithelial structure morphogenesis and differentiation. The presence of stromal cells promoted MEC proliferation, induced both alveolar and ductal morphogenesis and enhanced casein expression. In contrast, only alveolar structures were observed in monocultures. The alveolar structures generated from the heterotypic cultures in vitro exhibited proper polarity similar to human breast tissue in vivo. Consistent with their phenotypic appearance, more functional differentiation of epithelial cells was also observed in the heterotypic cultures, where casein-alpha and -beta mRNA expression were increased significantly. Additionally, this 3D multicellular culture model displayed an estrogen-responsive physiologically relevant response, evidenced by enhanced cell proliferation, aberrant morphology, changes in gene expression profile and few polarized lumen structures after estrogen treatment. This culture system offers an excellent opportunity to explore the role of cell-cell and cell-substrate interactions during mammary gland development, the consequences of hormone receptor activation on MEC behavior and morphogenesis, as well as their alteration during neoplastic transformation in human breast tissue. PMID- 22309837 TI - Coronary artery bypass grafting associated to aortic valve replacement in the elderly: survival and quality of life. AB - Myocardial ischemia is often associated to aortic valve stenosis in the elderly. Aim of this study was to evaluate the impact on survival and quality of life of CABG associated to aortic valve replacement in the septuagenarians and octogenarians.Between January 1991 and January 2010, 520 patients ageing > 70 years underwent aortic valve replacement with a mechanical prosthesis in two Institutions. They were divided into 2 groups: Group A included 406 patients undergoing isolated aortic valve replacement; Group B 114 patients receiving aortic valve replacement and CABG. A comparative analysis of long-term survival and quality of life (SF-36 test) was performed.Mean age was 74.2 +/- 3.6 years (74.3 +/- 3.6 in Group A, 74 +/- 3.3 in Group B; p = 0.33). Hospital mortality was 9.5% (46 patients). Twenty-nine (7.8%) in Group A and 17 in Group B (15.2%)(p = 0.019). Actuarial survival was 88.5% +/- 0.015 at 1 year, 81.9% +/- 0.02 at 5 years, 76.6% +/- 0.032 at 10 and 57.3 +/- 0.1 at 15 years. Ten-year survival was 77% +/- 0.034 in Group A and 77.8% +/- 0.045 in Group B (p = 0.2). Multivariate analysis did not reveal associated CABG as a predictor of long term mortality. The scores obtained in the SF-36 test were similar in the two groups and significantly higher than those of the general population matched for country, age and sex (p < 0.001 in all domains).Associated CABG determines a significant increase of hospital mortality in the elderly undergoing aortic valve replacement. Survivors did not show differences in long-term outcome and quality of life according to the presence of associated CABG. PMID- 22309838 TI - The combined treatment of praziquantel with osteopontin immunoneutralization reduces liver damage in Schistosoma japonicum-infected mice. AB - The aim of this study was to evaluate the therapeutic effects of osteopontin neutralization treatment on schistosome-induced liver injury in BALB/C mice. We randomly divided 100 BALB/C mice into groups A, B, C, D and group E. Mice in all groups except group A were abdominally infected with schistosomal cercariae to induce a schistosomal hepatopathological model. Mice in group C, D and group E were respectively administered with praziquantel, praziquantel plus colchicine and praziquantel plus neutralizing osteopontin antibody. We extracted mouse liver tissues at 3 and 9 weeks after the 'stool-eggs-positive' day, observed liver histopathological changes by haematoxylin-eosin and Masson trichrome staining and detected the expression of osteopontin, alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta (TGF-beta1) by immunohistochemistry, RT-PCR and Western blot. We found that praziquantel plus neutralizing osteopontin antibody treatment significantly decreased the granuloma dimension, the percentage of collagen and the expression of osteopontin, alpha-SMA and TGF-beta1 compared to praziquantel plus colchicine treatment in both the acute and chronic stage of schistosomal liver damage (P<0.05). So we believe that the combined regimen of osteopontin immunoneutralization and anti-helminthic treatment can reduce the granulomatous response and liver fibrosis during the schistosomal hepatopathologic course. PMID- 22309839 TI - Association study of 45 candidate genes in nicotine dependence in Han Chinese. AB - Numerous genetic linkages, association studies have been performed in different ethnic groups and revealed many susceptibility loci and genes for nicotine dependence. However, limited similar researches were performed in Han Chinese. This study was designed to investigate the association of candidate genes with nicotine dependence in Han Chinese. We genotyped 384 SNPs within 45 candidate genes with nicotine dependence in a Han Chinese population consisting 223 high nicotine dependent subjects and 257 low nicotine dependent subjects by employing GoldenGate genotyping assay (Illumina). Following association analysis was performed using PLINK software. Individual SNP-based association analysis revealed that nine SNPs located in DRD3 (rs2630351), DRD5 (rs1967550), MAP3K4 (rs2314378), DDC (rs11575461), CHRNB3 (rs4954), GABBR2 (rs2779562), DRD2 (rs11214613 and rs6589377) and CHRNA4 (rs2236196) were significantly associated with FTND after correction for multiple testing with the p values from 2.59*10( 7) to 9.99*10(-5). Haplotype-based association analysis revealed haplotype G-A-A formed by rs2630351, rs167771 and rs324032 and haplotype G-G-G-A formed by rs3773678, rs2630349, rs2630351 and rs167771 in DRD3; haplotype of G-A formed by rs2779562 and rs2808566 in GABBR2 and haplotype of T-T-A-G-A formed by rs6832644, rs4057797, rs9764, rs4552421 and rs10033119 in NPY1R are associated with FTND (p=3.61*10(-7)-8.78*10(-6)). Our results provided confirmation of the previous findings that DRD2, DRD3, DDC, CHRNB3, GABBR2 and CHRNA4 are associated with nicotine dependence. Furthermore, we for the first time report a significant association between nicotine dependence and DRD5, MAP3K4 and NPY1R. These findings need independent replication in the future studies. PMID- 22309840 TI - Resting energy expenditure assessment in anorexia nervosa: comparison of indirect calorimetry, a multisensor monitor and the Muller equation. AB - The aim of this study was to compare the estimations provided by three different means of measuring the resting energy expenditure (REE) in anorexia nervosa (AN) patients. REE was measured, after 24 h of refeeding, using a portable multisensor body monitor [SenseWear Pro2 Armband (SWA)], FitMateTM method and the Muller equation for individuals with body mass index < 18.5, the latter being based on dual-energy X-ray absorptiometry assessment of body composition. The mean differences between REE values estimated by SWA and those provided by the Muller equation and the FitMateTM method were significantly different from zero in both cases. In contrast, the mean differences between FitMateTM method and Muller equation were weakly significantly different from zero, and a significant correlation was noted between these two methods. In conclusion, the SWA does not appear to be an alternative to FitMateTM and Muller equation methods for assessing REE in AN patients. PMID- 22309841 TI - Membrane mechanisms for signal transduction: the coupling of the meso-scale raft domains to membrane-skeleton-induced compartments and dynamic protein complexes. AB - Virtually all biological membranes on earth share the basic structure of a two dimensional liquid. Such universality and peculiarity are comparable to those of the double helical structure of DNA, strongly suggesting the possibility that the fundamental mechanisms for the various functions of the plasma membrane could essentially be understood by a set of simple organizing principles, developed during the course of evolution. As an initial effort toward the development of such understanding, in this review, we present the concept of the cooperative action of the hierarchical three-tiered meso-scale (2-300 nm) domains in the plasma membrane: (1) actin membrane-skeleton-induced compartments (40-300 nm), (2) raft domains (2-20 nm), and (3) dynamic protein complex domains (3-10nm). Special attention is paid to the concept of meso-scale domains, where both thermal fluctuations and weak cooperativity play critical roles, and the coupling of the raft domains to the membrane-skeleton-induced compartments as well as dynamic protein complexes. The three-tiered meso-domain architecture of the plasma membrane provides an excellent perspective for understanding the membrane mechanisms of signal transduction. PMID- 22309842 TI - Therapeutic approaches to modulating Notch signaling: current challenges and future prospects. AB - Dysregulated Notch signaling has been implicated in numerous human diseases, including a broad spectrum of cancers. Mutations in Notch1 are prevalent in T cell acute lymphoblastic leukemia, and abnormal expression of different human Notch receptors contributes to B-cell tumors as well as cancers of the breast, lung, pancreas, skin, prostate, colon, brain and other tissues. Several gamma secretase inhibitors, small chemical compounds that were initially developed to inhibit the activity of the gamma-secretase aspartyl protease in Alzheimer's disease, are now being explored for their potential chemotherapeutic applications in Notch-associated cancers. An alternative approach involves the development of antibodies to inhibit specific Notch receptors, their activating ligands, or other components of the Notch pathway in tumors. Here we review recent progress and current challenges in the use of these strategies to modulate Notch signaling for cancer therapy. PMID- 22309843 TI - The double-edged sword of Notch signaling in cancer. AB - Recent deep sequencing of cancer genomes has produced an explosion of new data implicating Notch signaling in several human cancers. Unlike most other pathways, these data indicate that Notch signaling can be either oncogenic or tumor suppressive, depending on the cellular context. In some instances, these relationships were predicted from mouse models or presaged by developmental roles for Notch, but in other cases were unanticipated. This review discusses the pathogenic and translational significance of these new findings. PMID- 22309844 TI - Plant gene regulation in response to abiotic stress. PMID- 22309845 TI - Takayasu's arteritis is associated with HLA-B*52, but not with HLA-B*51, in Turkey. AB - INTRODUCTION: HLA-B*51 and HLA-B*52 are two close human leukocyte antigen (HLA) allele groups with minor amino acid differences. However, they are associated with two different vasculitides (HLA-B*51 in Behcet's disease and HLA-B*52 in Takayasu's arteritis (TAK)) and with major clinical and immunological differences. In this study, we aimed to screen a large cohort of TAK patients from Turkey for the presence of HLA-B*51 and HLA-B*52 as susceptibility and severity factors. METHODS: TAK patients (n = 330) followed at a total of 15 centers were included in the study. The mean age of the patients was 37.8 years, and 86% were women. DNA samples from the patients and healthy controls (HC; n = 210) were isolated, and the presence of HLA-B*51 or HLA-B*52 was screened for by using PCR with sequence-specific primers. RESULTS: We found a significant association of HLA-B*52 with TAK (20.9% vs HC = 6.7%, P = 0.000, OR = 3.7, 95% CI = 2.02 to 6.77). The distribution of HLA-B*51 did not differ between TAK patients and HCs (22.7% vs 24.8%, OR = 0.9, 95% CI = 0.60 to 1.34). The presence of HLA B*52 decreased in late-onset patients (> 40 years of age; 12.0%, P = 0.024, OR = 0.43, 95% CI = 0.20 to 0.91). Patients with angiographic type I disease with limited aortic involvement also had a lower presence of HLA-B*52 compared to those with all other disease subtypes (13.1% vs 26%, P = 0.005, OR = 0.43, 95% CI = 0.23 to 0.78). CONCLUSIONS: In this study, the previously reported association of TAK with HLA-B*52 in other populations was confirmed in patients from Turkey. The functional relevance of HLA-B*52 in TAK pathogenesis needs to be explored further. PMID- 22309846 TI - Development and preliminary validation of a behavioral task of negative reinforcement underlying risk-taking and its relation to problem alcohol use in college freshmen. AB - BACKGROUND: A long line of theoretical and empirical evidence implicates negative reinforcement as a process underlying the etiology and maintenance of risky alcohol use behaviors from adolescence through emerging adulthood. However, the bulk of this literature has relied on self-report measures, and there is a notable absence of behavioral modes of assessments of negative reinforcement based alcohol-related risk-taking. To address this clear gap in the literature, the current study presents the first published data on the reliability and validity of the Maryland Resource for the Behavioral Utilization of the Reinforcement of Negative Stimuli (MRBURNS), which is a modified version of the positive reinforcement-based Balloon Analogue Risk Task (BART). METHODS: Participants included a convenience sample of 116 college freshmen ever regular drinkers (aged 18 to 19) who completed both behavioral tasks; self-report measures of negative reinforcement/avoidance constructs and of positive reinforcement/appetitive constructs to examine convergent validity and discriminant validity, respectively; and self-report measures of alcohol use, problems, and motives to examine criterion validity. RESULTS: The MRBURNS evidenced sound experimental properties and reliability across task trials. In support of convergent validity, risk-taking on the MRBURNS correlated significantly with negative urgency, difficulties in emotion regulation, and depressive and anxiety-related symptoms. In support of discriminant validity, performance on the MRBURNS was unrelated to risk-taking on the BART, sensation seeking, and trait impulsivity. Finally, pertaining to criterion validity, risk taking on the MRBURNS was related to alcohol-related problems but not heavy episodic alcohol use. Notably, risk-taking on the MRBURNS was associated with negative reinforcement-based but not with positive reinforcement-based drinking motives. CONCLUSIONS: Data from this initial investigation suggest the utility of the MRBURNS as a behavioral measure of negative reinforcement-based risk-taking that can provide a useful complement to existing self-report measures to improve our understanding of the relationship between avoidant reinforcement processes and risky alcohol use. PMID- 22309847 TI - Pressure and pain in systemic sclerosis/scleroderma--an evaluation of a simple intervention (PISCES): randomised controlled trial protocol. AB - BACKGROUND: Foot problems associated with Systemic Sclerosis (SSc)/Scleroderma have been reported to be both common and disabling. There are only limited data describing specifically, the mechanical changes occurring in the foot in SSc. A pilot project conducted in preparation for this trial confirmed the previous reports of foot related impairment and reduced foot function in people with SSc and demonstrated a link to mechanical etiologies. To-date there have been no formal studies of interventions directed at the foot problems experienced by people with Systemic Sclerosis. The primary aim of this trial is to evaluate whether foot pain and foot-related health status in people with Systemic Sclerosis can be improved through the provision of a simple pressure-relieving insole. METHODS: The proposed trial is a pragmatic, multicenter, randomised controlled clinical trial following a completed pilot study. In four participating centres, 140 consenting patients with SSc and plantar foot pain will be randomised to receive either a commercially available pressure relieving and thermally insulating insole, or a sham insole with no cushioning or thermal properties. The primary end point is a reduction in pain measured using the Foot Function Index Pain subscale, 12 weeks after the start of intervention. Participants will complete the primary outcome measure (Foot Function Index pain sub-scale) prior to randomisation and at 12 weeks post randomisation. Secondary outcomes include participant reported pain and disability as derived from the Manchester Foot Pain and Disability Questionnaire and plantar pressures with and without the insoles in situ. DISCUSSION: This trial protocol proposes a rigorous and potentially significant evaluation of a simple and readily provided therapeutic approach which, if effective, could be of a great benefit for this group of patients. TRIAL REGISTRATION NUMBER: ISRCTN: ISRCTN02824122. PMID- 22309848 TI - Construction of synthetic regulatory networks in yeast. AB - Yeast species such as Saccharomyces cerevisiae have been exploited by humans for millennia and so it is therefore unsurprising that they are attractive cells to re-engineer for industrial use. Despite many beneficial traits yeast has for synthetic biology, it currently lags behind Escherichia coli in the number of synthetic networks that have been described. While the eukaryotic nature of yeast means that its regulation is not as simple to predict as it is for E. coli, once initial considerations have been made yeast is pleasingly tractable. In this review we provide a loose guide for constructing and implementing synthetic regulatory networks in S. cerevisiae using examples from previous research to highlight available resources, specific considerations and potential future advances. PMID- 22309849 TI - Insights into differential modulation of receptor function by hinge region using novel agonistic lutropin receptor and inverse agonistic thyrotropin receptor antibodies. AB - We report two antibodies, scFv 13B1 and MAb PD1.37, against the hinge regions of LHR and TSHR, respectively, which have similar epitopes but different effects on receptor function. While neither of them affected hormone binding, with marginal effects on hormone response, scFv 13B1 stimulated LHR in a dose-dependent manner, whereas MAb PD1.37 acted as an inverse agonist of TSHR. Moreover, PD1.37 could decrease the basal activity of hinge region CAMs, but had varied effects on those present in ECLs, whereas 13B1 was refractory to any CAMs in LHR. Using truncation mutants and peptide phage display, we compared the differential roles of the hinge region cysteine box-2/3 as well as the exoloops in the activation of these two homologus receptors. PMID- 22309850 TI - Most cancer can be prevented: we can do more. PMID- 22309851 TI - Efficacy of mycophenolate mofetil in severe mucocutaneous lichen planus: a retrospective review of 10 patients. AB - BACKGROUND: Ulcerative lichen planus is an uncommon and severe subtype of lichen planus primarily affecting the oral mucosal surfaces. It may be associated with significant morbidity and often requires immunosuppressive therapy to achieve disease control. There have been no previous reports in which objective outcome measures have been used to assess the efficacy of mycophenolate mofetil (MMF) in severe ulcerative lichen planus. OBJECTIVE: To evaluate the clinical responses of patients with severe ulcerative oral lichen planus who were treated with MMF at a tertiary oral medicine/dermatology centre. METHODS: This was a retrospective review of oral disease severity scores performed in 10 patients with recalcitrant ulcerative oral lichen planus (vulvovaginal-gingival, n = 8; penogingival, n = 1; oral, n = 1) before and after treatment with MMF therapy. The results were analysed using the Wilcoxon matched pairs signed-rank test. RESULTS: The mean duration of MMF treatment was 3.7 (SD +/- 2.4) years with a mean follow-up of 4.2 (SD +/- 2.7) years. The mean baseline oral disease severity scores (39.1 +/- 11.9) improved by 40% after 12-15 months (24.3 +/- 11.9, n = 8, P = 0.01) and by 43% after 21-24 months of MMF treatment (22.2 +/- 10.4, n = 9, P = 0.01). Of the 10 patients, six achieved remission, one had well-controlled disease and three had partially controlled disease. Two patients who achieved remission successfully discontinued treatment. MMF was well tolerated in all patients. CONCLUSION: Our case series demonstrates the efficacy and favourable side-effect profile of MMF in the treatment of severe ulcerative lichen planus. PMID- 22309852 TI - N-terminal disulfide-bridging of Borrelia outer surface protein C increases its diagnostic and vaccine potentials. AB - OspC is the main target for IgM in early-stage Lyme disease. As such it is employed as its native or recombinant form in routine immunoassays for the determination of Borrelia-specific antibodies. However, recombinant OspC has so far not shown the antigenicity of the native protein. The latter contains an intrinsic signal sequence and an adjacent cysteine residue, the attachment site of the lipid membrane anchor which has been discussed to have an adjuvant effect on the immune reaction. In expression experiments, we have found a recombinant variant, an OspC covalently homodimerized via an N-terminal disulfide bridge, that shows a remarkably enhanced antigenicity without lipid attachment. Three such OspCs derived from different Borrelia strains were subsequently expressed in E. coli and purified under non-reducing conditions. In non-reducing SDS-PAGE, OspC(Delta1-18) exhibited a 48-kDa band of dimeric OspC. When incubated with IgM OspC-positive human sera, the reaction at 48kDa was always stronger than at 24kDa of monomeric OspC(Delta1-18, C19G). A lineblot with OspC(Delta1-18) also showed a higher diagnostic accuracy than that obtained with OspC(Delta1-18, C19G) based on a higher affinity of IgM for the dimeric form. When used for the immunization of mice, dimeric OspC(Delta1-18) induced consistent high-titre antibodies against OspC, whereas OspC(Delta1-18, C19G) failed to provoke significant titres in some animals. We conclude that the disulfide-bridging of 2 OspC molecules via their N termini forms a complex that is more suitable for the determination of IgM-OspC and is a promising candidate for a monovalent vaccine. PMID- 22309853 TI - Occurrence of different Borrelia burgdorferi sensu lato genospecies including B. afzelii, B. bavariensis, and B. spielmanii in hedgehogs (Erinaceus spp.) in Europe. AB - In order to determine whether European hedgehogs (Erinaceus europaeus and E. roumanicus) play a role in the epidemiological cycle of Borrelia burgdorferi sensu lato in Central Europe and Great Britain, tissue samples of hedgehogs from Germany (n=211), Austria (n=4), the Czech Republic (n=22), and the U.K. (n=32) were tested for the presence of these tick-borne pathogens. PCR for amplification of the B. burgdorferi s.l.-specific 5S-23S intergenic spacer region as well as the outer surface protein A (ospA) gene were used. B. burgdorferi s.l. DNA was detected in 35 of the 259 E. europaeus and in 2 of 10 E. roumanicus. B. burgdorferi prevalences in E. europaeus ranged from 0% (U.K.) to 37.5% (Czech Republic), for E. roumanicus from 0% (Czech Republic) to 50.0% (Austria). Sequencing revealed the occurrence of 3 different B. burgdorferi genospecies in E. europaeus: B. afzelii was the dominant genospecies, followed by B. bavariensis (previously B. garinii OspA serotype 4) and B. spielmanii, the latter was detected for the first time in Hamburg (Germany). B. afzelii and B. bavariensis were also found in E. roumanicus. Our results suggest that hedgehogs modulate the epidemiology of certain species of the B. burgdorferi s.l. complex, potentially affecting the distribution and abundance of individual B. burgdorferi s.l. genospecies in various habitats. We hypothesise that juvenile or individuals with low immune competence in particular, have a high reservoir potential for the 3 genospecies identified here. PMID- 22309854 TI - Borrelia in Ethiopian ticks. AB - Two regions (Jimma and Dire Dawa) in Ethiopia were investigated for the presence of soft ticks. Although no Ornithodoros spp. ticks were collected during this survey, published records of their existence in Ethiopia were found. An overwhelming infestation of Argas persicus was revealed in a village located adjacent to Dire Dawa. These ticks primarily were feeding on poultry, but were also biting humans. Furthermore, hard ticks were collected from livestock and companion animals in these regions. Collected ticks were assessed for Borrelia by real-time PCR followed by conventional PCR and sequencing to identify species present. A. persicus ticks were found to carry B. anserina in 3 of 40 (7.5%) A. persicus tick pools, whilst hard tick pools yielded 2 of 16 (12.5%) positive for B. theileri. Collectively, these borrelial species and their tick vectors are likely to have an important economic impact of particular relevance to subsistence farmers in Ethiopia. PMID- 22309855 TI - Differential salivary gland transcript expression profile in Ixodes scapularis nymphs upon feeding or flavivirus infection. AB - Ixodid ticks are vectors of human diseases such as Lyme disease, babesiosis, anaplasmosis, and tick-borne encephalitis. These diseases cause significant morbidity and mortality worldwide and are transmitted to humans during tick feeding. The tick-host-pathogen interface is a complex environment where host responses are modulated by the molecules in tick saliva to enable the acquisition of a blood meal. Disruption of host responses at the site of the tick bite may also provide an advantage for pathogens to survive and replicate. Thus, the molecules in tick saliva not only aid the tick in securing a nutrient-rich blood meal, but can also enhance the transmission and acquisition of pathogens. To investigate the effect of feeding and flavivirus infection on the salivary gland transcript expression profile in ticks, a first-generation microarray was developed using ESTs from a cDNA library derived from Ixodes scapularis salivary glands. When the salivary gland transcript profile in ticks feeding over the course of 3 days was compared to that in unfed ticks, a dramatic increase in transcripts related to metabolism was observed. Specifically, 578 transcripts were up-regulated compared to 151 down-regulated transcripts in response to feeding. When specific time points post attachment were analyzed, a temporal pattern of gene expression was observed. When Langat virus-infected ticks were compared to mock-infected ticks, transcript expression changes were observed at all 3 days of feeding. Differentially regulated transcripts include putative secreted proteins, lipocalins, Kunitz domain-containing proteins, anti-microbial peptides, and transcripts of unknown function. These studies identify salivary gland transcripts that are differentially regulated during feeding or in the context of flavivirus infection in Ixodes scapularis nymphs, a medically important disease vector. Further analysis of these transcripts may identify salivary factors that affect the transmission or replication of tick-borne flaviviruses. PMID- 22309856 TI - Goats and sheep as sentinels for tick-borne encephalitis (TBE) virus- epidemiological studies in areas endemic and non-endemic for TBE virus in Germany. AB - The aim of the study was to examine grazing goats and sheep as specific sentinels for characterization of the tick-borne encephalitis virus (TBEV)-related risk in an area by means of serosurveillance tests in the German federal states Baden Wuerttemberg, Bavaria, Thuringia, North Rhine-Westphalia, Lower Saxony, Schleswig Holstein, and Mecklenburg-West Pomerania. A total of 3590 sheep sera and 3793 goat sera was collected in 2003 and 2006-2009 and were examined by ELISA screening and confirmed by serum neutralization test. Considerable differences in seroprevalence were seen between single flocks in districts in Baden Wuerttemberg, Bavaria, and Thuringia with values between 0 and 43% which confirmed the patchy pattern of TBEV foci that can range in size from very small to large. The here described serological screening may be a helpful tool for an early warning system of a potential TBEV risk. Testing of 1700 ticks by real-time RT-PCR in two districts in Baden-Wuerttemberg revealed only one positive tick, thus illustrating the problems of expensive and time-consuming tick collection. PMID- 22309857 TI - Distribution and infection frequency of 'Candidatus Rickettsia amblyommii' in Maryland populations of the lone star tick (Amblyomma americanum) and culture in an Anopheles gambiae mosquito cell line. AB - Amblyomma americanum (the lone star tick) is a broadly distributed tick that transmits multiple pathogens of humans and domestic animals. 'Candidatus Rickettsia amblyommii' is a spotted-fever group rickettsial species that is potentially associated with human disease. In 2008 and 2009, we assayed over 500 unfed adult ticks from 19 Maryland populations for the presence of 'Candidatus R. amblyommii'. Infection frequencies ranged from 33% to 100%, with an average infection rate of 60% in 2008 and 69% in 2009. Infection frequencies did not differ statistically between sexes. To develop a system in which to study 'Candidatus R. amblyommii' in the laboratory, we used a cell line developed from Anopheles gambiae mosquitoes (Sua5B) to isolate and culture 'Candidatus R. amblyommii' from field-collected A. americanum ticks from 2 localities in Maryland. After infection, Sua5B cells were infected for more than 40 passages. Infection was confirmed by Rickettsia-specific PCR, gene sequencing, and Rickettsia-specific fluorescence in situ hybridization (FISH). These data show that 'Candidatus R. amblyommii' is widespread in Maryland A. americanum populations and that Sua5B cells are a useful tool for culturing Rickettsia infections from wild ticks. PMID- 22309858 TI - Tick-borne rickettsiae in Guinea and Liberia. AB - While the high seroprevalence for the rickettsiae that cause spotted fevers and the multiple pathogenic rickettsiae is known, the data on the distribution of rickettsial diseases in Africa are often incomplete. We collected ticks from domestic or wild animals (generally a source of bushmeat) that were in contact with humans in 2 neighboring countries of tropical West Africa, Guinea and Liberia. In total, 382 ticks representing 6 species were collected in Liberia and 655 ticks representing 7 species were collected in Guinea. We found rickettsiae in 9 different species of ticks from both countries. Rickettsia africae was found in 93-100% of Amblyomma variegatum, in 14-93% of Rhipicephalus (B.) geigyi, Rh. (B.) annulatus, and Rh. (B.) decoloratus, and in several Hyalomma marginatum rufipes and Haemaphysalis paraleachi. A genetic variant of R. africae was found in Amblyomma compressum. R. massiliae was found in 10/61 (16%) of Rh. senegalensis ticks and in 2% of Haemaphysalis paraleachi ticks collected from dogs. We identified a new rickettsia in one of 44 (2%) Ixodes muniensis collected from a dog in Liberia. As this rickettsia is not yet isolated, we propose the provisional name "Candidatus Rickettsia liberiensis" (for the West African country where the host tick was collected). PMID- 22309859 TI - The European hedgehog (Erinaceus europaeus)--a suitable reservoir for variants of Anaplasma phagocytophilum? AB - The European hedgehog (Erinaceus europaeus) is a common insectivore in most parts of Europe and is frequently infested by the ticks Ixodes ricinus and I. hexagonus. I. ricinus ticks have been found infected with Anaplasma phagocytophilum, an obligate intracellular bacterium, but little is known about the potential of the hedgehog as a reservoir host. In this study, the infection with A. phagocytophilum and the genetic variants involved were investigated in a captive hedgehog population which was kept in a fenced, natural grass and bush garden habitat, and also in its ticks. Additionally hedgehogs from hedgehog caretaking stations were investigated. EDTA blood and ticks were collected from the captive hedgehog population once a month from March to October 2007 and in March and April 2008. All 3 developmental stages of I. ricinus and I. hexagonus occurred on the hedgehogs. After DNA extraction, the samples were screened for A. phagocytophilum with a real-time PCR, and selected samples were further investigated with a nested PCR targeting the partial 16S rRNA gene, followed by sequencing. One hundred thirty-six out of 220 hedgehog blood samples (61.8%) from altogether 48 individuals, 413 out of 563 I. ricinus samples and 90 out of 338 I. hexagonus samples were PCR-positive. Thirty-two hedgehogs were positive more than once, most frequently twice or 3 times, but also up to 9 times. Sequencing of the partial 16S rRNA gene resulted in 6 variants, but one variant ('A') was the most frequent which appeared in 93.8% of the positive hedgehogs. This variant (equaling Frankonia II, GenBank AF136712) has recently been reported from human, equine, and canine granulocytic anaplasmosis cases and thus, its specific association with hedgehogs is an important finding in the epidemiology of A. phagocytophilum in Europe. The high infection rate of both hedgehogs and ticks with A. phagocytophilum and the simultaneous infestation with 2 tick species of all developmental stages suggest that the hedgehog may be a suitable reservoir for at least some variants of A. phagocytophilum. PMID- 22309860 TI - Molecular detection of Anaplasma marginale infection in carrier cattle. AB - Anaplasma marginale infections are responsible for widespread morbidity and mortality particularly in crossbred and exotic breeds of cattle in the tropics and subtropics. In the present study, a semi-nested PCR assay was utilized for the detection of A. marginale infection in carrier cattle from different areas of Punjab state, India. An amplicon of 458 bp specific for msp5 of A. marginale was detected in 45.2% of blood samples when subjected to primary PCR assay against the routine blood smear examination, which revealed inclusion bodies in only 12.5% of samples. Semi-nested PCR employing product of samples negative by primary PCR produced the amplicons of desired size (345 bp) in 51% (29/57) of samples indicating that nested PCR, when coupled with primary PCR, resulted in increased sensitivity in detection of A. marginale infection in carrier cattle from 45.2 to 73.1%. These results suggest higher threshold detection limits of the nested PCR over the conventional technique used for diagnosis of anaplasmosis which is ideally suited for diagnosis of carrier cases which act as nidus for the spread of the infection to the susceptible stock in endemic areas. PMID- 22309861 TI - Morphological records of oocyte maturation in the parthenogenetic tick Amblyomma rotundatum Koch, 1844 (Acari: Ixodidae). AB - Oocyte maturation in the thelytokous parthenogenetic tick Amblyomma rotundatum was examined for the first time using light and scanning electron microscopy. The panoistic ovary lacks nurse and follicular cells and is a single continuous tubular structure forming a lumen delimited by the ovarian wall. Oocytes of tick species are usually classified according to cytoplasm appearance, the presence of germinal vesicle, the presence of yolk granules, and the chorion. However, for this species, we also use oocyte size as an auxiliary tool since most oocytes were in stages I-III and were histologically very similar. Oocytes were classified into five development stages, and specific characteristics were observed: mature oocytes with thin chorion, pedicel cells arranged forming an epithelium with two or more oocytes attached by the same structure, and a large number of oocytes in the process of reabsorption. PMID- 22309863 TI - Thank you! PMID- 22309864 TI - Treating aggressive periodontitis. AB - The purpose of Linking Research to Clinical Practice is to present evidence based information to clinical dental hygienists so that they can make informed decisions regarding patient treatment and recommendations. Each issue will feature a different topic area of importance to clinical dental hygienists with A BOTTOM LINE to translate the research findings into clinical application. PMID- 22309865 TI - Oral health literacy in the dental office: the unrecognized patient risk factor. AB - According to the report Healthy People 2010, oral health literacy is the degree to which individuals have the capacity to obtain, process and understand basic health information and services needed to make appropriate oral health decisions. Studies have linked a patient's health literacy to a variety of significant health behaviors, statuses and outcomes. This article provides an overview of the literature concerning the levels of health literacy among adults in the U.S., the effects of literacy levels on treatment and patient outcomes, literacy assessment in the practice setting and the effects of a patient's literacy on communication with a dental health provider. The implications of inadequate patient oral health literacy on the practice of dental hygienists and communication recommendations are discussed, as is the need for future research specifically on oral health literacy. PMID- 22309866 TI - Dental diagnostics: molecular analysis of oral biofilms. AB - Dental biofilms are complex, multi-species bacterial communities that colonize the mouth in the form of plaque and are known to cause dental caries and periodontal disease. Biofilms are unique from planktonic bacteria in that they are mutualistic communities with a 3-dimensional structure and complex nutritional and communication pathways. The homeostasis within the biofilm colony can be disrupted, causing a shift in the bacterial composition of the colony and resulting in proliferation of pathogenic species. Because of this dynamic lifestyle, traditional microbiological techniques are inadequate for the study of biofilms. Many of the bacteria present in the oral cavity are viable but not culturable, which severely limits laboratory analysis. However, with the advent of new molecular techniques, the microbial makeup of oral biofilms can be better identified. Some of these techniques include DNA-DNA hybridization, 16S rRNA gene sequencing, denaturing gradient gel electrophoresis, terminal restriction fragment length polymorphism, denaturing high-performance liquid chromatography and pyrosequencing. This review provides an overview of biofilm formation and examines the major molecular techniques currently used in oral biofilm analysis. Future applications of the molecular analysis of oral biofilms in the diagnosis and treatment of caries and periodontal disease are also discussed. PMID- 22309867 TI - Diabetes and oral health: the importance of oral health-related behavior. AB - PURPOSE: The objective of this study was to explore oral health-related behavior, how patients with diabetes differ from patients not diagnosed with diabetes in their oral health and whether oral health-related behavior moderates the oral health status of patients with diabetes. METHODS: Survey and chart review data were collected from 448 patients (52% male, 48% female, average age: 57 years) of which 77 were diagnosed with diabetes (17%). RESULTS: Patients with diabetes had a higher percentage of teeth with mobility than those not diagnosed with diabetes (14% vs. 8%, p=0.023), as well as gingival recession (16% vs. 12%, p=0.035) and more teeth with recession in the esthetic zone (1.17 vs. 0.88, p=0.046). They also had more decayed, missing and filled surfaces due to caries (101 vs. 82, p<0.001) and more missing teeth due to caries (11 vs. 7, p<0.001). Patients with diabetes brushed and flossed less frequently. Patients with diabetes who did not brush regularly had poorer periodontal health (percentage of teeth with probing depth of <4 mm: 82% vs. 60%, p=0.039, 4 to 6 mm: 34% vs. 17%, p=0.059) and more caries (percentage of decayed teeth: 32% vs. 15%, p=0.033) than regularly brushing patients with diabetes. CONCLUSION: Educating patients with diabetes about the importance of good oral self care needs to become a priority for their oral health care providers. PMID- 22309868 TI - Use of complementary and alternative medicine for work-related pain correlates with career satisfaction among dental hygienists. AB - PURPOSE: Chronic musculoskeletal pain (CMSP) is associated with work stress and burn-out among registered dental hygienists, with prevalence estimates ranging between 64 to 93%. Complementary and alternative medicine (CAM) therapies can be helpful in managing CMSP. The purpose of this study was to determine if dental hygienists who use CAM have greater career satisfaction compared to conventional therapy (CT) users. METHODS: ADHA members (n=2,431) in North Carolina (n=573) and California (n=1,858) were surveyed. Data were analyzed using univariate and bivariate analyses and logistic regression. RESULTS: A response rate of 25.3% (n=617) was obtained, revealing that 76.5% (n=472) suffered from CMSP. The use of CAM or CT was reported among 80.7% (n=381) of dental hygienists with CMSP. CAM users reported greater overall health (79.3% vs. 54.0%, p<0.001), career satisfaction (59.2% vs. 39.0%, p<0.001) and were able to work the hours they wanted (69.8% vs. 64.0%, p<0.001) compared to CT users. Of those with CMSP, 36.4% (n=172) considered a career change and 13.0% (n=59) reported having left dental hygiene. Those with CMSP were less likely to recall that ergonomics were taught or reinforced during clinical training. CONCLUSION: CAM therapies may improve quality of life, reduce work disruptions and enhance career satisfaction for dental hygienists who suffer from CMSP. Ergonomics education may help reduce the number of hygienists who suffer from CMSP. Increased student awareness of CMSP risk is needed to reduce CMSP in the future by enhancing ergonomics education and incorporating CAM, such as yoga stretches, into the classroom and clinic routine. PMID- 22309869 TI - California dental hygienists' knowledge, attitudes and practices regarding herbal and dietary supplements. AB - PURPOSE: As more Americans use dietary supplements, the potential for increased adverse effects increases. The purpose of this study was to identify the current knowledge, attitudes and practice behaviors among California dental hygienists regarding herbal and dietary supplements (HDS). METHODS: A stratified random sample of 1,203 registered California hygienists were surveyed. The survey included items about personal characteristics as well as questions regarding knowledge, attitudes and beliefs and practice behavior about HDS. Three primary outcomes were analyzed: dental hygienists' knowledge about HDS, attitudes (confidence) about HDS and behavior practices (communication) regarding HDS. Confirmatory factor analysis was performed. Personal characteristics were assessed in stepwise multiple linear regression analysis for impact on knowledge scores. RESULTS: The response rate was 21% (n=249). Dental hygienists have low levels of knowledge and confidence about HDS, as well as poor communication practices related to HDS. California dental hygienists scored a low mean of 38% on their knowledge of HDS. On the confidence scale (standardized range of 0 to 10 possible), hygienists scored 3.67+/-2.03. On the communication practices subscales (standardized range of 0 to 10 possible), hygienists scored 4.21+/-2.99 on general communication practices and 1.25+/-1.66 on specific communication practices. Dental hygienists who were members of the California Dental Hygienists' Association and attended a continuing education course on HDS within the last year or who personally used HDS scored significantly higher in knowledge, confidence and communication practices than their counter parts. These 3 attributes were identified as significant predicators for higher knowledge about HDS. CONCLUSION: There is a need to improve California dental hygienists' knowledge and involvement in the active management of patients who take HDS. Such actions can be expected to improve oral health outcomes. Focused training on HDS for hygienists should be designed to improve their knowledge and influence practice behaviors. PMID- 22309870 TI - Comparison of dental hygiene clinical instructor and student opinions of professional preparation for clinical instruction. AB - PURPOSE: The purpose of this study was to determine the degree of professional preparation among clinical instructors employed in baccalaureate dental hygiene programs in the U.S. and to examine clinical instructors' and students' perceived need for educational preparation. The data-generating sample consisted of 285 dental hygiene clinical students and 76 dental hygiene clinical instructors from the 48 dental hygiene programs in the U.S. that offered a baccalaureate or higher degree in dental hygiene. METHODS: Online survey instruments contained both qualitative and quantitative questions and were completed by 285 clinical dental hygiene students and 76 clinical dental hygiene instructors from dental hygiene programs in the U.S. Using descriptive statistics, Chi-square analysis and the Mann-Whitney U test, the data from clinical dental hygiene instructors and students were compared to determine if the preparation in educational methods being offered to dental hygiene clinical instructors was meeting the perceived needs of both clinical dental hygiene students and instructors. RESULTS: According to dental hygiene clinical students (n=285), 60% (n=171) indicated that 6 to 10 years of clinical dental hygiene experience was optimal, while 37% of clinical instructors (n=28) identified having less than 5 years of clinical experience prior to clinical teaching. Therefore, the majority of clinical instructors have less than optimal years of clinical dental hygiene experience prior to clinical instructing. Regarding methods of pre-employment preparation, more than half (n=40) of the dental hygiene clinical instructors (n=76) reported most professional preparation occurred through informal discussion with fellow clinical instructors. Significant differences were found between the clinical dental hygiene instructors' and clinical dental hygiene students' opinions of importance of clinical instructors being given formal guidance in educational methodologies (p=0.002), communication skills (p=0.027), grading and evaluation techniques (p=0.001) and use of technology (p=0.008). Although the majority of instructors and students rated training in teaching methods and communication skills as most important, the majority of clinical dental hygiene instructors (74%, n=53) identified grading and evaluation techniques as the most addressed subject of training. CONCLUSION: Both dental hygiene clinical instructors and students identified areas of potential improvement in the professional educational guidance of dental hygiene clinical instructors. Dental hygiene clinical education may benefit from including formal clinical instructor pre employment preparation programs. PMID- 22309871 TI - Oral hygiene knowledge and practice among Dinka and Nuer from Sudan to the U.S. AB - PURPOSE: The purpose of this study was to determine knowledge and use of oral hygiene methods for refugees from Sudan now living in the U.S. prior to conducting elective implant surgery. METHODS: The sample included 34 adults of the Dinka or Nuer tribes who participated in 1 or more phases of a project to restore 6 lower anterior teeth with implants. An English language survey was administered by an interpreter for whom Dinka or Nuer was a first language. Each interpreter underwent an elective restorative procedure prior to acting as an interpreter. The project survey covered demographics, traditional and current oral hygiene practices, perceived aesthetics and dental visits since arrival to the U.S. RESULTS: Data analyses revealed that male participants outnumbered female participants, and all were under 30 years of age. Traditional dental practices paralleled Western oral hygiene methods and current oral hygiene involved 1 brushing event per day and prevalent toothpick use. Most participants wished to have all teeth in place, bright white coloration and a maxillary diastema. Few had visited a U.S. dental facility more than once, and none were using biannual checkups to maintain dental health. All participants required detailed oral hygiene education to fill the knowledge gap between traditional and U.S. systems and to maintain their newly restored dental health status. CONCLUSION: Refugees arriving to the U.S. from a non-Western country may be in great need of Western oral hygiene training to create or maintain a high dental health status. Resettlement programs should include dental screening, treatment and oral hygiene training to prevent further decline in dental health status. PMID- 22309872 TI - Assessment of the University of Michigan's dental hygiene partnership with the Huron Valley Boys & Girls Club: a study of students' and staffs' perceptions and service learning outcomes. AB - PURPOSE: The Boys & Girls Club of America (BGCA) requires a health curriculum be taught. With the assistance of the University of Michigan (UM) Dental Hygiene program, these requirements have been addressed at the Huron Valley Boys & Girls Club (HVBGC) through dental hygiene students presenting oral health education to club members throughout the year. This study assessed the outcomes and benefits of the service learning initiative between the UM Dental Hygiene Program and the HVBGC from both the students' and staffs' perceptions. METHODS: Three surveys were distributed: one to the HVBGC staff, one to UM's Dental Hygiene class of 2012 (with no service learning experience at the HVBGC) and one to UM Dental Hygiene classes of 2010 and 2011 (most of whom had experience at the HVBGC). Qualitative and quantitative data were collected and evaluated. RESULTS: The respondents from the class of 2012 were less knowledgeable about the BGCA and access to care issues. The members of the classes of 2010 and 2011, 79% of whom had HVBGC experience, identified they had benefitted from this service learning experience. The HVBGC staff survey indicated a high level of satisfaction with the student presentations and felt their curricular requirements were being met. Future topics of safety, orthodontics and gardening/nutrition were identified. CONCLUSION: This study indicates the service learning initiative has been beneficial for both the UM Dental Hygiene students and the HVBGC. Future studies should use a longitudinal design to obtain baseline and post-service learning data. PMID- 22309873 TI - Factors affecting the performance of oral cancer screenings by Texas dental hygienists. AB - PURPOSE: The 5 year survival rates for oral cancer have not changed in the last 50 years. A simple intra- and extra-oral examination provided by health care professionals could help to reduce morbidity and mortality of oral cancer. This study focused on Texas dental hygienists' performance of oral cancer screenings (OCS) and factors that influenced their performance of this examination. METHODS: A 33 question survey of 608 randomly selected Texas dental hygienists was conducted. Frequency, chi-square and Spearman correlation tests were performed. RESULTS: Three hundred and six hygienists replied and provided the data for this study. The data indicated that 45.8% "always" performed OCS, 23.5% performed OCS at the initial appointment and 47.4% at the recall appointment. Experience and comfort level were the greatest influences on OCS performance. Dental hygienists practicing for 16 or more years performed OCS 51.2% of the time, while those with only 0 to 5 years of experience performed OCS 25.5% of the time. A statistically significant correlation (rho=0.15, p<0.007) was found be tween years of experience and performance of OCS. A significant correlation (rho=0.18, p<0.001) was found between the identification of a suspicious lesion and the performance of OCS. Forty-nine percent of dental hygienists reported feeling "very comfortable" with intra-oral examinations, but only 26.5% felt "very comfortable" with extra-oral examinations. A statistically significant correlation (rho=0.16, p<0.001) was found between comfort level in the performance of an OCS and reported frequency of OCS. The majority of subjects performed poorly on the knowledge portion of the survey (mean=53%). There was a significant correlation (rho=0.22, p<0.001) between attendance at OCS continuing education courses and the performance of OCS. CONCLUSION: Dental hygienists' knowledge about oral cancer was not current and comfort levels with performing OCS were low. These indicate a need for a stronger emphasis on the importance of OCS for students during dental hygiene education and a more thorough continuing education for practicing dental hygienists. PMID- 22309874 TI - Predicting National Dental Hygiene Board Examination success based on specific admission factors. AB - PURPOSE: The purpose of this study was to determine if there are specific admissions criteria that are significantly correlated with a student's National Board Dental Hygiene Examination (NBDHE) total score and case-based score. Specifically, the study examined the relation between an individual's reading acuity and their scores on the NBDHE. Because of the competitive nature of most dental hygiene admissions, selecting those applicants who are more likely to be successful in the academic program and pass the NBDHE is critical. METHODS: Total NBDHE scores and case-based scores of 214 students attending Western Kentucky University's Program of Dental Hygiene between 2002 and 2010 were examined to determine if significant correlations existed. Specific factors examined were each student's total NBDHE score, as well as the score on the case-based section of the examination, age, microbiology lecture grade, microbiology lab grade, anatomy and physiology grade, college GPA, English grade, psychology grade, composite ACT score and subcomponent scores of the ACT (math, reading, English and science). RESULTS: Results revealed that the strongest predictors of total NBDHE scores were the score on the reading portion of the ACT (r=0.715, r2=0.511, p=0.01) and the grades in Microbiology lecture (r=0.644, r2=0.414, p=0.01). Results revealed that the strongest predictors of scores on the case-based portion of the NBDHE were students' scores on the reading portion of the ACT (r=0.673, r2=0.452, p=0.01) and the microbiology lecture grade (r = .637, r2 = .405, p = 0.01). CONCLUSION: Traditionally, schools have looked at specific science-based pre-requisite courses as a means of determining admission to schools of dental hygiene. Findings from this study suggest that a broader approach may need to be taken, specifically as it concerns a student's reading aptitude. PMID- 22309875 TI - Financial management practices and attitudes of dental hygienists: a descriptive study. AB - PURPOSE: The purpose of this study was to determine the financial management goals and practices of registered dental hygienists, their satisfaction with their current financial situations and their attitudes about savings, investments and retirement. METHODS: A 40 question electronic survey was completed by 388 registered dental hygienists. The descriptive instrument assessed financial practices, attitudes, goals and beliefs, retirement mindset, savings habits, debt tendencies and demographic characteristics of respondents. Statistical analyses compared respondents' beliefs about their financial independence and security with their current financial practices. Analyses included: independent samples t tests, chi-square analysis and ANOVA. RESULTS: Most dental hygienists believed themselves to be financially independent and reported satisfaction with their current financial situation. Significant relationships existed between respondents' satisfaction with their current financial situations and their financial attitudes and practices (saving regularly and having limited debt). Those who indicated they had personally saved for retirement were more likely to view these savings as their largest source of income during retirement, as opposed to Social Security benefits. A majority agreed that financial management education should be included in the dental hygiene curriculum, and that they would attend a continuing education course on the subject if offered. CONCLUSION: The results of this study suggest that hygienists have confidence in their ability to provide secure financial futures for themselves. Hygienists who practiced sound financial planning, such as adhering to monthly budgets, having wills, lowering debt and saving regularly, reported a higher level of financial security than those who did not. Most respondents expressed interest in receiving education about financial management through the dental hygiene curriculum and continuing education courses. PMID- 22309876 TI - Repetitive coronal polishing yields minimal enamel loss. AB - PURPOSE: The American Dental Hygienists' Association recommends selective polishing because of risk of enamel removal and lack of documented therapeutic value. The initial study documenting enamel loss from polishing used methods not acceptable for clinical use, while results from other studies are inconsistent. This study examines the effect of simulated life-time polishing on enamel thickness. Enamel loss from polishing is compared to the enamel thickness just coronal to the cementoenamel junction (CEJ) to relate results to clinical application. METHODS: Eight premolars and 18 molars were polished 150 times with coarse prophy paste, then pre- and post-polishing micrometer measurements were compared. Eight unpolished premolars and 18 unpolished molars were used as control groups. Average enamel thickness from 10 premolars and 10 molars just coronal to the CEJ was chosen to represent minimal enamel thickness, and was calculated using digital radiography. T-tests were used to compare group means. RESULTS: The mean measurement difference was significantly higher for the premolar treatment group than the control group, but no difference was noted between molar treatment and control groups. Neither treatment group demonstrated significant abrasion when compared to average minimal enamel thickness. Root abrasion was noted on 5 molars. CONCLUSION: The results of our study indicate that polishing may remove enamel, but the quantity removed is unlikely to be clinically relevant. Root surface abrasion seen on molars is disturbing, considering stain often occurs on exposed mandibular anterior root surfaces and may cause repeated and prolonged polishing. Further investigation into alternative stain removal methods is recommended. PMID- 22309877 TI - Hormonal, functional and genetic biomarkers in controlled ovarian stimulation: tools for matching patients and protocols. AB - Variability in the subfertile patient population excludes the possibility of a single approach to controlled ovarian stimulation (COS) covering all the requirements of a patient. Modern technology has led to the development of new drugs, treatment options and quantitative methods that can identify single patient characteristics. These could potentially be used to match patients with the right treatment options to optimise efficacy, safety and tolerability during COS. Currently, age and follicle-stimulating hormone (FSH) level remain the most commonly used single patient characteristics in clinical practice. These variables only provide a basic prognosis for success and indications for standard COS treatment based on gross patient categorisation. In contrast, the anti Mullerian hormone level appears to be an accurate predictor of ovarian reserve and response to COS, and could be used successfully to guide COS. The antral follicle count is a functional biomarker that could be useful in determining the dose of FSH necessary during stimulation and the success of treatment. Finally, in the future, genetic screening may allow an individual patient's response to stimulation during COS to be predicted based on genotype. Unfortunately, despite the predictive power of these measures, no single biomarker can stand alone as a guide to determine the best treatment option. In the future, hormonal, functional and genetic biomarkers will be used together to personalise COS. PMID- 22309878 TI - Functioning of the TA cassette of streptococcal plasmid pSM19035 in various Gram positive bacteria. AB - Toxin-antitoxin (TA) systems are common in microorganisms and are frequently found in the chromosomes and low-copy number plasmids of bacterial pathogens. One such system is carried by the low copy number plasmid pSM19035 of the pathogenic bacterium Streptococcus pyogenes. This plasmid encodes an omega-epsilon-zeta cassette that ensures its stable maintenance by post-segregational killing of plasmid-free cells. In this study, the activity of the omega-epsilon-zeta cassette was examined in various Gram-positive bacteria with a low G/C content in their DNA. The broad host range of pSM19035 was confirmed and the copy number of a truncated derivative in transformed strains was determined by real-time qPCR. PMID- 22309879 TI - Esophageal diameter is decreased in some patients with eosinophilic esophagitis and might increase with topical corticosteroid therapy. AB - BACKGROUND & AIMS: The rapid response to topical corticosteroids makes it hard to implicate fibrosis as the cause of dysphagia in patients with eosinophilic esophagitis (EoE). We examined surrogates of esophageal expansion using minimal and maximal esophageal diameter (EDmin and EDmax) in barium swallow examinations. METHODS: Eleven patients evaluated at Mayo Clinic, Rochester (8 female, median age 40, median diagnosis 36 months, median symptom duration 132 months) underwent barium esophagrams to determine EDmin and EDmax before and after 6 weeks of topical corticosteroid therapy. We assessed parameter reproducibility (in healthy volunteers), baseline EDmin and EDmax, postcorticosteroid changes in EoE patients, and correlation with clinical response. RESULTS: EDmin and EDmax were reproducible, with nonsignificant variance in the 2 esophagrams in control subjects (P = .44 and P = .66, respectively). Baseline EDmax was reduced in EoE at 19 mm (range, 13-26 mm) vs 24 mm (range, 19-29 mm) in controls (P = .004). About 50% of the EoE patients had EDmax and min values within the 10th to 90th percentile of controls (45% and 55%, respectively). Clinical improvement by Mayo Dsyphagia Questionnaire did not correlate with postcorticosteroid luminal change (P = .19 for EDmax; P = .75 for EDmin). Median increases in postcorticosteroid EDmax and EDmin were not statistically significant (P = .15 and .1, respectively). However, they were significant in patients with abnormal baseline EDmax (n = 6; 2 mm; P = .01) and EDmin (n = 5; 3 mm; P = .02). CONCLUSIONS: Esophageal diameter is a reproducible parameter that is frequently decreased in EoE, but normal in approximately 50% of patients. Those with narrowing might respond to steroids, but it is unclear if narrowing causes dysphagia. PMID- 22309880 TI - Cardiac tamponade from a giant thymoma: case report. AB - Thymoma, the most common neoplasm of the anterior mediastinum especially in adults, accounts for 20-25% of all mediastinal tumors and 50% of anterior mediastinal masses. These tumors are routinely asymptomatic for prolonged periods of time. Pericardial tamponade is a very rare initial manifestation of a thymoma. This report presents a patient who had hemorrhagic pericardial tamponade that likely resulted from the largest symptomatic mixed type (type AB) thymoma described in the literature. PMID- 22309881 TI - Self-determined motivational predictors of increases in dental behaviors, decreases in dental plaque, and improvement in oral health: a randomized clinical trial. AB - OBJECTIVE: The present study tested the hypotheses that: (a) a dental intervention designed to promote dental care competence in an autonomy-supportive way, relative to standard care, would positively predict perceived clinician autonomy support and patient autonomous motivation for the project, increases in autonomous motivation for dental home care, perceived dental competence, and dental behaviors, and decreases in both dental plaque and gingivitis over 5.5 months; and (b) the self-determination theory process model with the intervention and individual differences in autonomy orientation positively predicting project autonomous motivation and increases in perceived dental competence, both of which would be associated with increases in dental behavior, which would, in turn, lead to decreased plaque and gingivitis. METHODS: A randomized two-group experiment was conducted at a dental clinic with 141 patients (Mage = 23.31 years, SD = 3.5), with pre- and postmeasures (after 5.5 months) of motivation variables, dental behaviors, dental plaque, and gingivitis. RESULTS: Overall, the experimental and hypothesized process models received strong support. The effect sizes were moderate for dental behavior, large for autonomous motivation for the project and perceived competence, and very large for perceived autonomy support, dental plaque, and gingivitis. A structural equation model supported the hypothesized process model. CONCLUSIONS: Considering the very large effects on reductions in dental plaque and gingivitis, promoting dental care competence in an autonomy-supportive way, relative to standard care, has important practical implications for dental treatment, home care, and health. PMID- 22309882 TI - Red potato chips: segmentation cues can substantially decrease food intake. AB - OBJECTIVE: To discover a scalable method of food-packaging presentation, which can help reduce per occasion food consumption by making portions sizes more salient and segmented. METHODS: Two studies of American undergraduates who ate from tubes of potato chips while watching a movie. In each study, participants ate chips that were either identical (the control group) or which had colored chips inserted at regular intervals (the treatment groups). One treatment group had a distinctively different (reddish) chip present at every 7th (Study 1) or 5th (Study 2) chip, and the 2nd treatment group had one present every 14th (Study 1) or 10th (Study 2) chip. Measures were the number of chips consumed and (in Study 1) the participants estimates of how many they believed they consumed. RESULTS: In both studies, chip consumption was reduced by more than 50%, averaging across the 2 segmentation intervals, with no significant difference between the 2 intervals. Estimates of amount consumed were much more accurate when there was segmentation. CONCLUSION: Segmenting a package effectively reduced consumption in the settings we have explored. Segmentation cues may operate by any or all of 3 mechanisms: (a) they call attention to and encourage better monitoring of eating, (b) they suggest smaller consumption (portion size) norms, or (c) they break automated eating sequences by introducing a pause. There is some evidence from the 1st study that provides evidence for the 1st, monitoring account. PMID- 22309883 TI - Pathways from childhood intelligence and socioeconomic status to late-life cardiovascular disease risk. AB - OBJECTIVE: C-reactive protein (CRP) is an acute-phase marker of systemic inflammation and considered an established risk marker for cardiovascular disease (CVD) in old age. Previous studies have suggested that low childhood intelligence, lower socioeconomic status (SES) in childhood or in later life, unhealthy behaviors, poor wellbeing, and high body mass index (BMI) are associated with inflammation. Life course models that simultaneously incorporate all these risk factors can explain how CVD risks accumulate over time, from childhood to old age. METHODS: Using the data from 1,091 Scottish adults (Lothian Birth Cohort Study, 1936), a path model was constructed to predict CRP at age 70 from concurrent health behaviors, self-perceived quality of life, and BMI and adulthood SES as mediating variables, and from parental SES and childhood intelligence as distal risk factors. RESULTS: A well-fitting path model (CFI = .92, SRMR = .05) demonstrated significant indirect effects from childhood intelligence and parental social class to inflammation via BMI, health behaviors and quality of life (all ps < .05). Low childhood intelligence, unhealthy behaviors, and higher BMI were also direct predictors of CRP. CONCLUSIONS: The life course model illustrated how CVD risks may accumulate over time, beginning in childhood and being both direct and transmitted indirectly via low adult SES, unhealthy behaviors, impaired quality of life, and high BMI. Knowledge on the childhood risk factors and their pathways to poor health can be used to identify high-risk individuals for more intensive and tailored behavior change interventions, and to develop effective public health policies. PMID- 22309884 TI - Positive media portrayals of obese persons: impact on attitudes and image preferences. AB - OBJECTIVE: The purpose of this research was to assess the impact of nonstereotypical, positive media portrayals of obese persons on biased attitudes, as well as propose a change in media practices that could reduce public weight bias and consequent negative health outcomes for those who experience weight stigma. METHOD: Two online experiments were conducted in which participants viewed either a stigmatizing or a positive photograph of an obese model. In Experiment 1 (N = 146), participants viewed a photograph of either a Caucasian or African American obese woman; in Experiment 2 (N = 145), participants viewed either a Caucasian male or female obese model. Multiple linear regression models were used to analyze outcomes for social distance attitudes toward the obese models depicted in the images, in addition to other negative attitudes and image preferences. RESULTS: Participants who viewed the stigmatizing images endorsed stronger social distance attitudes and more negative attitudes toward obese persons than participants who viewed the positive images, and there was a stronger preference for the positive images than the stigmatizing images. These results were consistent regardless of the race or gender of the obese model pictured. CONCLUSION: The findings indicate that more positive media portrayals of obese individuals may help reduce weight stigma and its associated negative health outcomes. PMID- 22309886 TI - A common genetic background could explain early-onset Crohn's disease. AB - Crohn's disease (CD) is a multifactorial disease, in which environmental, microbial and genetic factors play important roles. CD is characterized by a chronic granulomatous inflammation by necrotic scarring with aspects of full thickness wall. In spite of affecting mainly young adults, sometimes, CD can be present in the first year of life (early onset Crohn disease, EOCD) showing an unpredictable course and being often more severe than at older ages. In this paper we propose the hypothesis that EOCD patients should be analyzed using a Mendelian approach with family studies aimed to identify new loci directly involved in the early onset Crohn's disease. So we will leave the classic association study approach used until now for the identification of genes responsible for susceptibility to CD and propose linkage family analysis as alternative and powerful tool for the identification of new genetic variants associated with familiar cases of EOCD. PMID- 22309885 TI - Randomized controlled trial of a comprehensive home environment-focused weight loss program for adults. AB - OBJECTIVE: Behavioral weight-loss programs (BWL) provide limited instruction on how to change the environmental context of weight-regulating behaviors, perhaps contributing to regain. Drawing on social ecological models, this trial evaluated a comprehensive weight-loss program that targeted both an individual's behavior and his or her physical and social home environment. METHOD: Overweight and obese adults (N = 201; 48.9 +/- 10.5 years; 78.1% women) were randomized to BWL or to BWL plus home-environment changes (BWL + H). Groups met weekly for 6 months and bimonthly for 12 months. BWL + H participants were given items to facilitate healthy choices in their homes (e.g., exercise equipment, portion plates) and attended treatment with a household partner. Weight loss at 6 and 18 months was the primary outcome. RESULTS: BWL + H changed many aspects of the home environment and produced better 6-month weight losses than BWL (p = .017). At 18 months, no weight-loss differences were observed (p = .19) and rates of regain were equivalent (p = .30). Treatment response was moderated by gender (6 months, p = .011; 18 months, p = .006). Women lost more weight in BWL + H than BWL at 6 and 18 months, whereas men in BWL lost more weight than those in BWL + H at 18 months. Partners, regardless of gender, lost more weight in BWL + H than BWL at both time points (ps < .0001). CONCLUSION: The home food and exercise environment is malleable and targeting this microenvironment appears to improve initial weight loss, and in women, 18-month outcomes. Research is needed to understand this gender difference and to develop home-focused strategies with more powerful and sustained weight-loss effects. PMID- 22309887 TI - Coronary angiography--a curative procedure? AB - There is increasing evidence, currently mainly subjective that, in addition to the diagnostic role; coronary angiography may have some degree of therapeutic effect, at least in some patients. Patients' experiences and known biological properties of the contrast media lend credence to this possibility and should be a spur for proper studies of the hypothesis. PMID- 22309888 TI - Human laboratory paradigms in alcohol research. AB - BACKGROUND: Human laboratory studies have a long and rich history in the field of alcoholism. Human laboratory studies have allowed for advances in alcohol research in a variety of ways, including elucidating neurobehavioral mechanisms of risk, identifying phenotypically distinct subtypes of alcohol users, investigating the candidate genes underlying experimental phenotypes for alcoholism, and testing mechanisms of action of alcoholism pharmacotherapies on clinically relevant translational phenotypes, such as persons exhibiting positive like alcohol effects or alcohol craving. Importantly, the field of human laboratory studies in addiction has progressed rapidly over the past decade and has built upon earlier findings of alcohol's neuropharmacological effects to advancing translational research on alcoholism etiology and treatment. METHODS AND RESULTS: To that end, the new generation of human laboratory studies has focused on applying new methodologies, further refining alcoholism phenotypes, and translating these findings to studies of alcoholism genetics, medication development, and pharmacogenetics. The combination of experimental laboratory approaches with the recent developments in neuroscience and pharmacology has been particularly fruitful in furthering our understanding of the impact of individual differences in alcoholism risk and in treatment response. CONCLUSIONS: This review of the literature focuses on human laboratory studies of subjective intoxication, alcohol craving, anxiety, and behavioral economics. Each section discusses opportunities for phenotype refinement under laboratory conditions, as well as its application to translational science of alcoholism. A summary and recommendations for future research are also provided. PMID- 22309889 TI - Neutropenia at baseline could indicate poor prognosis in low/intermediate risk myelodysplastic syndrome patients. PMID- 22309890 TI - AZA-ESA combo: a new standard for higher risk MDS? PMID- 22309891 TI - Sequential array comparative genomic hybridization analysis identifies copy number changes during blastic transformation of chronic myeloid leukemia. AB - The present study was performed to provide direct evidence on copy number changes during progression from chronic phase (CP) to blastic phase (BP) in chronic myeloid leukemia (CML) through a longitudinal follow-up study. Matched CP and BP samples in three patients were analyzed using high-resolution array comparative genomic hybridization (aCGH) chips. During blastic transformation, loss of large genomic segments including 6q14.1-q22.31, chromosome 7 and 9p13.2-p21.3 were noted. Furthermore, small-sized copy number changes involving cancer-associated genes were observed. In addition, we identified a novel fusion gene consisted of PAX5 and MLLT3 (AF9). It is likely that blastic transformation of CML is a multi step process associated accumulation of several genomic events which may largely overlap with those found in acute leukemias. PMID- 22309892 TI - One-pot synthesis of block copolymers in supercritical carbon dioxide: a simple versatile route to nanostructured microparticles. AB - We present a one-pot synthesis for well-defined nanostructured polymeric microparticles formed from block copolymers that could easily be adapted to commercial scale. We have utilized reversible addition-fragmentation chain transfer (RAFT) polymerization to prepare block copolymers in a dispersion polymerization in supercritical carbon dioxide, an efficient process which uses no additional solvents and hence is environmentally acceptable. We demonstrate that a wide range of monomer types, including methacrylates, acrylamides, and styrenics, can be utilized leading to block copolymer materials that are amphiphilic (e.g., poly(methyl methacrylate)-b-poly(N,N-dimethylacrylamide)) and/or mechanically diverse (e.g., poly(methyl methacrylate)-b-poly(N,N dimethylaminoethylmethacrylate)). Interrogation of the internal structure of the microparticles reveals an array of nanoscale morphologies, including multilayered, curved cylindrical, and spherical domains. Surprisingly, control can also be exerted by changing the chemical nature of the constituent blocks and it is clear that selective CO(2) sorption must strongly influence the block copolymer phase behavior, resulting in kinetically trapped morphologies that are different from those conventionally observed for block copolymer thin films formed in absence of CO(2). PMID- 22309893 TI - Low copy number of the FCGR3B gene and rheumatoid arthritis: a case-control study and meta-analysis. AB - INTRODUCTION: Low copy number (CN) of the Fc gamma receptor 3B (FCGR3B) gene has been associated with systemic autoimmune disease. This receptor for IgG is present almost exclusively on neutrophils and plays a role in their interaction with immune complexes. At present the relationship between FCGR3B and rheumatoid arthritis (RA) is unclear. The aim of the present study was to investigate whether low CN of the FCGR3B gene is associated with susceptibility to RA. METHOD: The FCGR3B CN was determined using a custom Taqman(r) CN assay (Hs04211858; Applied Biosystems, Foster City, CA, USA) in 197 RA patients, recruited from a tertiary setting, and in 162 population matched controls. Odds ratios for low CN (< 2) and high CN (> 2), both relative to the normal diploid 2CN, were estimated by logistic regression. RESULTS: A significant association between RA and low FCGR3B CN was observed, with frequencies of 13.7% in RA patients compared with 6.2% in controls (odds ratio 2.5, 95% confidence interval 1.2 to 5.4, P = 0.017). No association was observed between low CN and the presence of rheumatoid factor, anti-cyclic citrullinated peptide antibodies or radiographic erosions in RA patients. A meta-analysis including six previous studies confirmed an association between RA and low FCGR3B CN (odds ratio 1.47, 95% confidence interval 1.13 to 1.92, P = 0.004). CONCLUSIONS: The present study confirms that a low CN of the FCGR3B gene is associated with susceptibility to RA. The association may be stronger in patients recruited from a tertiary setting, which may relate to disease severity and/or complications. The mechanism of susceptibility remains unclear and further study is required. PMID- 22309894 TI - LUBAC, a novel ubiquitin ligase for linear ubiquitination, is crucial for inflammation and immune responses. AB - LUBAC (linear ubiquitin chain assembly complex) is a ubiquitin ligase complex composed of SHARPIN, HOIL-IL and HOIP that generates linear polyubiquitin chains and regulates the NF-kappaB pathway, which is pivotal in inflammatory and immune responses. Recent findings on the regulation of NF-kappaB by LUBAC and the diseases associated with this process are the focus of this review. PMID- 22309895 TI - The activity of drug-metabolizing enzymes and the biotransformation of selected anthelmintics in the model tapeworm Hymenolepis diminuta. AB - The drug-metabolizing enzymes of some helminths can deactivate anthelmintics and therefore partially protect helminths against these drugs' toxic effect. The aim of our study was to assess the activity of the main drug-metabolizing enzymes and evaluate the metabolism of selected anthelmintics (albendazole, flubendazole, mebendazole) in the rat tapeworm Hymenolepis diminuta, a species often used as a model tapeworm. In vitro and ex vivo experiments were performed. Metabolites of the anthelmintics were detected and identified by HPLC with spectrofluorometric or mass-spectrometric detection. The enzymes of H. diminuta are able to reduce the carbonyl group of flubendazole, mebendazole and several other xenobiotics. Although the activity of a number of oxidation enzymes was determined, no oxidative metabolites of albendazole were detected. Regarding conjugation enzymes, a high activity of glutathione S-transferase was observed. A methyl derivative of reduced flubendazole was the only conjugation metabolite identified in ex vivo incubations of H. diminuta with anthelmintics. The results revealed that H. diminuta metabolized flubendazole and mebendazole, but not albendazole. The biotransformation pathways found in H. diminuta differ from those described in Moniezia expanza and suggest the interspecies differences in drug metabolism not only among classes of helminths, but even among tapeworms. PMID- 22309896 TI - The problem of nitrogen disposal in the obese. AB - Amino-N is preserved because of the scarcity and nutritional importance of protein. Excretion requires its conversion to ammonia, later incorporated into urea. Under conditions of excess dietary energy, the body cannot easily dispose of the excess amino-N against the evolutively adapted schemes that prevent its wastage; thus ammonia and glutamine formation (and urea excretion) are decreased. High lipid (and energy) availability limits the utilisation of glucose, and high glucose spares the production of ammonium from amino acids, limiting the synthesis of glutamine and its utilisation by the intestine and kidney. The amino acid composition of the diet affects the production of ammonium depending on its composition and the individual amino acid catabolic pathways. Surplus amino acids enhance protein synthesis and growth, and the synthesis of non-protein-N containing compounds. But these outlets are not enough; consequently, less conventional mechanisms are activated, such as increased synthesis of NO? followed by higher nitrite (and nitrate) excretion and changes in the microbiota. There is also a significant production of N(2) gas, through unknown mechanisms. Health consequences of amino-N surplus are difficult to fathom because of the sparse data available, but it can be speculated that the effects may be negative, largely because the fundamental N homeostasis is stretched out of normalcy, forcing the N removal through pathways unprepared for that task. The unreliable results of hyperproteic diets, and part of the dysregulation found in the metabolic syndrome may be an unwanted consequence of this N disposal conflict. PMID- 22309897 TI - Fracture of the anterior segment of the atrophic mandible related to dental implants. AB - Implant placement in an anterior atrophic mandible is not an uncommon procedure. Fracture secondary to such implant placement is a rare complication. The authors discuss a case referred to their surgical centre and discuss the management approaches found in the English literature. PMID- 22309898 TI - Determinants of bioelectrical phase angle in disease. AB - Phase angle (PhA), a parameter of bioelectrical impedance analysis, is a well known predictor of morbidity and mortality in various diseases. The causes of decreased PhA are, however, not yet completely understood. We therefore investigated determinants of PhA in 777 hospitalised patients in a retrospective analysis. PhA was assessed by bioelectrical impedance analysis at 50 KHz. Subjective global assessment (SGA) was used to evaluate nutritional status. Age, sex, BMI as well as nutritional status (SGA), benign or malignant disease and C reactive protein (CRP) were investigated as potential determinants of PhA and standardised PhA (SPhA) = (observed PhA - mean PhA of reference values)/standard deviation of reference values in a general linear model regression analysis. Next to age (estimated effect size, 46.6%; P<0.0001), malnutrition (39.1%; P<0.0001) emerged as a major PhA determinant in our study population. Moreover, sex (6.4%; P<0.0001), CRP (4.4%; P<0.0001) and BMI (3.5%; P < 0.0001) exhibited a significant influence on PhA, whereas malignant disease showed no significant effect in this model. The only significant determinants of SPhA were malnutrition (85.4%; P<0.0001) and inflammation (9.6 %; P<0.0001). In conclusion, next to the established predictors, malnutrition and inflammation have a strong impact on PhA in sick individuals, which partly explains its prognostic power. When investigating the SPhA, only malnutrition and inflammation were found to be significant predictors, as a result of which the SPhA is considered a more suitable indicator of nutritional and health status. PMID- 22309899 TI - Effect of narrowband ultraviolet B therapy on inflammatory markers and body fat composition in moderate to severe psoriasis. AB - BACKGROUND: Previous studies have shown increased prevalence of metabolic syndrome in patients with psoriasis. OBJECTIVES: To characterize the anthropometric and metabolic profile of Spanish patients with moderate to severe psoriasis compared with controls without psoriasis matched for gender, age and body mass index (BMI), and to evaluate the impact of narrowband ultraviolet B (NB UVB) therapy on patient profiles. METHODS: Baseline waist circumference, body fat composition, lipid, carbohydrate and calcium metabolism profile, inflammation markers, homocysteine, vitamins D, B(6) and B(12) and folic acid of 50 patients with psoriasis and 50 matched controls were recorded then evaluated after NB-UVB in patients with psoriasis and correlated with clinical outcome. RESULTS: Despite very similar BMIs, 54% of patients met International Diabetes Foundation criteria for metabolic syndrome compared with 42% of controls (P = 0.01); body fat was 29.9% in patients and 28.0% in controls (P = 0.037), correlating with waist circumference; while patient atherogenic profiles were less favourable, with higher apolipoprotein B and low density lipoprotein cholesterol than controls, and both patients and controls showed insufficient vitamin D serum levels (< 20 ng mL(-1)). Mean improvement of Psoriasis Area and Severity Index (PASI) after NB UVB was 78.2%. Ferritin, B(12) and C-reactive protein decreased significantly after NB-UVB therapy. Vitamin D levels reached adequate levels after phototherapy; however, no relationship with PASI improvement was observed. CONCLUSIONS: We characterized inflammatory and atherogenic profiles of Spanish patients with psoriasis compared with matched controls. After NB-UVB therapy we demonstrated improvement in psoriasis and some systemic inflammation markers, which were not mediated by enhancement of vitamin D synthesis. PMID- 22309900 TI - Debate. How should steps per day be reported--a proposal using data from Africa. AB - Recent reviews published in the IJBNPA provide more definitive ranges of ambulatory activity usually found in four general age groups, and how step data relates to public health guidelines. Of note in these reviews was the lack of data from Developing Countries. Apart from the lack of published data, available data was not presented in a format conducive to inclusion in the reviews. Consequently, this paper presents available pedometry data from Africa, such that it is easily available for inclusion in future comparisons. Also addressed is the need to consider adjusting prevalence data according to standard population age structures. PMID- 22309901 TI - Electroacupuncture for control of blood glucose in diabetes: literature review. AB - Electrical stimulation at acupuncture points (acupoints) has been investigated for its utility in lowering blood glucose in hyperglycemic humans and animal models. Only two studies were found using electroacupuncture in human subjects, and in both of these, the participants were normal (nondiabetic) and electrical stimulation was carried out at several acupoints. It had a hypoglycemic effect in obese women with calorific restriction diet using electrical stimulation of 2 Hz for 30 minutes/day for 20 days, but no change occurred in blood glucose of fasted patients in the other study using 1 Hz for 15 minutes. Fourteen animal studies were found, of which, 11 were performed in diabetic and normal rats. A hypoglycemic effect was observed in fasted type 1 diabetic rats using the Zusanli (ST36) leg acupoint with electrical stimulation of 15 Hz for 30 minutes and 60 minutes. In fasted type 2 diabetic rats, blood glucose was lowered using the Zusanli acupoint with electrical stimulation parameters of 15 Hz and 10 mA for 30 minutes. Also, using the Zhongwan (CV12) abdomen acupoint with electrical stimulation parameters of 15 Hz and 10 mA for 90 minutes had a hypoglycemic effect in fasted type 2 diabetic rats. In fasted normal rats, electrical stimulation of 2 Hz or 15 Hz for 30 minutes at the Zusanli or Zhongwan acupoint caused a decrease in blood glucose. Future studies are required in fasted diabetic rats to determine the effect of electroacupuncture on blood levels of insulin, lipids, fatty acids and beta-endorphin, and blood flow and nerve conduction velocity. Studies with fasted normal and diabetic human subjects treated by electroacupuncture are warranted using data from animal experiments to inform such studies. PMID- 22309902 TI - Electro-acupuncture stimulation at acupoints reduced the severity of hypotension during anesthesia in patients undergoing liver transplantation. AB - BACKGROUND: Patients with end-stage liver diseases who undergo liver transplantation may suffer from hypotension related to the liver disease itself or related to the surgical procedure. Because electro-acupuncture (EA) at the Neiguan (PC-6) and the Jianshi (PC-5) points influences hemodynamics, we hypothesize that electro-acupuncture at the traditionally used acupuncture points will reduce the severity of hypotension in patients who undergo liver transplantation. METHODS: Forty patients with end-stage liver disease who underwent orthotropic deceased donor liver transplantation were randomized into two groups. The norepinephrine (NE) group received norepinephrine as a vasoconstrictor, and the electro-acupuncture group received EA at the PC-5 and the PC-6 points for treatment of hypotension during anesthesia for the liver transplantation. The patients were monitored, during the three stages of liver transplantation by using hemodynamic parameters. RESULTS: During the three stages of liver transplantation, there were no significant differences in the hemodynamic measurements including the mean arterial pressure, heart rate and central venous pressure between the two groups (p>0.05). CONCLUSIONS: Electro acupuncture at the acupuncture points reduced the severity and the incidence of hypotension during anesthesia for liver transplantation. PMID- 22309903 TI - A naturalistic study of the effect of acupuncture on heart-rate variability. AB - OBJECTIVES: To study the effect of acupuncture on heart rate variability (HRV) by using linear and non-linear methods of analysis. METHODS: 40 patients were recruited consecutively, including patients with insomnia, stomachache, diarrhea, dizziness, cervical syndrome, lower back pain, gonarthritis, peripheral facial paralysis, post-traumatic organic brain syndrome and urinary retention. Different acupoint prescriptions were used, according to the textbook for 5-years' education on traditional Chinese medicine specialty, which is used in Chinese Universities. HRV was recorded before, during, and after acupuncture. RESULTS: Acupuncture substantially reduced variability, causing a 41% reduction in the standard deviation. Using a Fourier analysis, the variances both in the low frequency (LF) and the high frequency (HF) ranges were markedly reduced, but the LF/HF ratio (an indication of sympatho-vagal balance) was not altered. The HR was unchanged. The sample entropy, which is a measure of the complexity of time series, was significantly increased (+35%). CONCLUSIONS: Acupuncture produced a pattern of changes different from that seen in pathological conditions, where increased variability and reduced complexity is expected. PMID- 22309904 TI - Blood fluidity enhancement by electrical acupuncture stimulation is related to an adrenergic mechanism. AB - We have reported that electrical acupuncture stimulation (ACU) increases blood fluidity by decreasing platelet aggregation. In this study, we investigated the mechanism causing the increase of blood fluidity. The effects of ACU on blood fluidity and platelet adhesion were examined using a Micro Channel Array Flow Analyzer (MC-FAN) and a laser scattering platelet aggregometer (PA-20). Male Wistar rats (7-8 weeks old) were used in the study. ACU (1 or 100 Hz, 3-5 V), which causes slight muscle twitching, was applied to the ZuSanli (ST-36) acupoint for 15 or 60 minutes once/day. Blood samples were collected from the inferior vena cava. ACU applied to ST-36 revealed significant increases in blood fluidity, while platelet adhesion activity decreased, regardless of the difference of stimulus time. The acupuncture had an immediate effect. Even if naloxone was administered during acupuncture stimulus, the blood flow time shortened in a similar way, as in the only acupuncture stimulus group. In addition, the effect of acupuncture on blood fluidity was inhibited by a beta-antagonist. The results indicate that ACU affects blood fluidity depending on the acupoints, and that the effect of ACU might involve an endogenous adrenergic mechanism. PMID- 22309905 TI - Moxibustion at mingmen reduces inflammation and decreases IL-6 in a collagen induced arthritis mouse model. AB - The purpose of this study was to compare the effectiveness of moxibustion (MOX) treatment at the GV4 and CV12 acupoints, and to determine the correlations between MOX treatment and interleukin (IL)-6 and corticosterone levels in a collagen-induced arthritis (CIA) mouse model. CIA mice were immunized twice intradermally over a 3-week interval with bovine type II collagen. After the second immunization (day 21), MOX was applied to the mouse equivalent of the GV4 and CV12 acupoints with a 1mg moxa cone five times/day. Clinical symptoms of CIA were observed three times/week until day 35. The concentrations of IL-6 and corticosterone in the blood samples were measured by immunoassay kits. At day 35, the incidence of CIA was significantly decreased in mice treated with MOX at the GV4 acupoint (78%, n=23, p<0.05), compared to untreated CIA mice (100%) and mice treated with MOX at the CV12 acupoint (100%). IL-6 and corticosterone levels were significantly increased by immunization. IL-6 levels significantly decreased in mice treated with MOX at the GV4 acupoint. These results suggest that MOX treatment suppressed CIA at the GV4 acupoint, not at the CV12 acupoint, possibly through inhibition of IL-6 production. PMID- 22309906 TI - High capacity optical channels for bioinformation transfer: acupuncture meridians. AB - Mammalian bodies are hierarchical systems whose internal cooperation and coherent activity require high capacity information transfer between the central control unit--the brain--and the periphery--the organs. A communication system capable of meeting information capacity requirements should be based on transmission of electromagnetic signals. Structures that fulfill requirements for such information transfer have not yet been analyzed. Acupuncture meridians have been demonstrated experimentally in some animals. They might represent systems of information transfer between the brain and the peripheral organs. The ducts of the meridians may correspond to optical fibers operating from the far infrared to the visible wavelength region. The main features of a model of the duct as an optical fiber are delineated and its properties outlined. However, to analyze essentials of the transmission capabilities, the whole meridian structure should be mapped and a more comprehensive set of physical parameters measured. In particular, experimental data concerning morphological arrangements of ordered water in the ducts and corpuscles, and a complete content of the biological particles in the flowing water and its permittivity are missing. PMID- 22309907 TI - Retrosplenial cortex is involved in analgesia induced by 2- but not 100-Hz electroacupuncture in the rat tail-flick test. AB - This study examined whether or not the antinociceptive effect of 2- or 100-Hz electroacupuncture (EA) depends on the integrity of the retrosplenial cortex (RSC). Rats were taken for determination of tail-flick latency before and after injection of saline or 2% lidocaine (0.25 MUl) into the retrosplenial cortex (RSC) bilaterally. Five minutes later, they were submitted to a 20-minute period of 2 Hz, 100 Hz, or sham EA at the Zusanli and Sanyinjiao acupoints bilaterally, and tail-flick latency was measured within 30 seconds after the end of stimulation and at 5-minute intervals for up to 30 minutes. EA at a frequency of either 2 or 100 Hz induced a strong and long-lasting inhibition of the tail-flick reflex in rats treated with saline (0.25 MUl) injected into the RSC. The analgesia produced by 2-Hz EA lasted for a shorter time in lidocaine-treated rats. By contrast, RSC impairment did not change the analgesic effect of 100 Hz EA. The integrity of the RSC is implicated in the duration of analgesia induced by low-frequency EA but is not essential for the analgesic effects evoked by high frequency EA. PMID- 22309908 TI - Industrial toxicants and Parkinson's disease. AB - The exposure of the human population to environmental contaminants is recognized as a significant contributing factor for the development of Parkinson's disease (PD) and other forms of parkinsonism. While pesticides have repeatedly been identified as risk factors for PD, these compounds represent only a subset of environmental toxicants that we are exposed to on a regular basis. Thus, non pesticide contaminants, such as metals, solvents, and other organohalogen compounds have also been implicated in the clinical and pathological manifestations of these movement disorders and it is these non-pesticide compounds that are the subject of this review. As toxic exposures to these classes of compounds can result in a spectrum of PD or PD-related disorders, it is imperative to appreciate shared clinico-pathological characteristics or mechanisms of action of these compounds in order to further delineate the resultant disorders as well as identify improved preventive strategies or therapeutic interventions. PMID- 22309910 TI - Discovery of non-oxime reactivators using an in silico pharmacophore model of oxime reactivators of OP-inhibited acetylcholinesterase. AB - We earlier reported an in silico pharmacophore model for reactivation of oximes to tabun-inhibited AChE. Since DFP (diisopropylfluorophosphate) like tabun is a G agent simulator, we utilized the model as a rational strategy to discover non oxime reactivators of DFP-inhibited AChE in this study. The phramacophore was used for virtual screening of two commercial databases, Maybridge and ChemNavigator, to identify reactivators which lack the oxime functions. The procedure led us to identify several potent non-oxime compounds that reactivate DFP-inhibited AChE. These non-oxime reactivators contain a nucleophile group in lieu of the oxime moiety in the compound. Five of these novel non-oximes showed Kr values within ten-fold of 2-PAM in an in vitro assay. The pharmacophore model contained a hydrogen bond acceptor, a hydrogen bond donor, and an aromatic ring features distributed in a 3D space. Calculated stereoelectronic properties reported earlier with respect to the location of molecular orbitals and electrostatic potentials were consistent with the model and the newly identified compounds. Down selection of compounds after virtual screening was performed on the basis of fit score to the model, conformational energy, and in silico evaluations for favorable blood-brain barrier (BBB) penetrability, octanol-water partition (log P), and toxicity (rat oral LD(50)) assessments. In vitro reactivation efficacy of the compounds was evaluated in a DFP-inhibited eel acetylcholinesterase assay. PMID- 22309909 TI - Synthesis, in vitro binding studies and docking of long-chain arylpiperazine nitroquipazine analogues, as potential serotonin transporter inhibitors. AB - It is well known that 6-nitroquipazine exhibits about 150-fold higher affinity for the serotonin transporter (SERT) than quipazine and recently we showed quipazine buspirone analogues with high to moderate SERT affinity. Now we have designed and synthesized several 6-nitroquipazine buspirone derivatives. Unexpectedly, their SERT binding affinities were moderate, and much lower than that of the previously studied quipazine buspirone analogues. To explain these findings, docking studies of both groups of compounds into two different homology models of human SERT was performed using a flexible target-ligand docking approach (4D docking). The crystal structures of leucine transporter from Aquifex aeolicus in complex with leucine and with tryptophan were used as templates for the SERT models in closed and outward-facing conformations, respectively. We found that the latter conformation represents the most reliable model for binding of buspirone analogues. Docking into that model showed that the nitrated compounds acquire a rod like shape in the binding pocket with polar groups (nitro and imido-) at the ends of the rod. 6-Nitro substituents gave steric clashes with amino acids located at the extracellular loop 4, which may explain their lower affinity than corresponding quipazine buspirone analogues. The results from the present study may suggest chemical design strategies to improve the SERT modulators. PMID- 22309911 TI - Synthesis and biological evaluation of quinazoline and quinoline bearing 2,2,6,6 tetramethylpiperidine-N-oxyl as potential epidermal growth factor receptor(EGFR) tyrosine kinase inhibitors and EPR bio-probe agents. AB - 4-anilinoquinazoline and 4-anilinoquinoline scaffolds bearing a 2,2,6,6 tetramethylpiperidine-N-oxyl(TEMPO) have been synthesized and evaluated for their ability to inhibit EGFR tyrosine kinase and A431 cell lines. Compared to their corresponding parent compounds, all of the new compounds bearing a TEMPO showed more efficient inhibition for EGFR and A431 cells. Furthermore, we have proved that these molecules bearing a TEMPO can exactly get into A431 cells exerting inhibitory effect that may be used for EPR detecting. In our docking model, quinazolines bearing a TEMPO on either 6- or 3-positions took different linking modes according to EGFR crystal structure. In contrast to their parent compounds, these new TEMPO-derived analogues possessed compatible inhibitory effect that might be useful as potential EGFR inhibitors and as EPR bio-probes. PMID- 22309912 TI - Design, synthesis and biological evaluation of 6-substituted aminocarbonyl benzimidazole derivatives as nonpeptidic angiotensin II AT1 receptor antagonists. AB - A series of 6-substituted aminocarbonyl benzimidazole derivatives were designed and synthesized as nonpeptidic angiotensin II AT(1) receptor antagonists. The preliminary pharmacological evaluation revealed nanomolar AT(1) receptor binding affinity and good AT(1) receptor selectivity over AT(2) receptor for all compounds of the series, a potent antagonistic activity in isolated rabbit aortic strip functional assay for compounds 6b, 6d and 6i was also demonstrated. Furthermore, evaluation in spontaneous hypertensive rats and a preliminary toxicity evaluation showed that compound 6i is an orally active AT(1) receptor antagonist with low toxicity. PMID- 22309913 TI - Inhibition of monoamine oxidase by selected C6-substituted chromone derivatives. AB - Chromone has been reported to be a useful scaffold for the design of monoamine oxidase (MAO) inhibitors. In an attempt to discover highly potent MAO inhibitors and to contribute to the known structure-activity relationships (SAR) of MAO inhibition by chromones, in the present study, we have synthesized a series of chromone derivatives substituted at C6 with a variety of alkyloxy substituents, and evaluated the resulting compounds as inhibitors of recombinant human MAO-A and -B. The results document that the C6-substituted chromones are potent reversible MAO-B inhibitors with IC(50) values in the low nM range (2-76 nM). The chromones were also found to bind reversibly to MAO-A, but with lower affinities compared to MAO-B. It may therefore be concluded that C6-substituted chromones are highly potent MAO-B selective inhibitors and promising lead compounds for the development of therapy for neurodegenerative disorders such as Parkinson's disease. The results of this study are discussed with reference to possible binding orientations of a selected C6-substituted chromone in the active site cavities of MAO-A and -B. PMID- 22309914 TI - Synthesis, characterization and antiamoebic activity of some hydrazone and azole derivatives bearing pyridyl moiety as a promising heterocyclic scaffold. AB - In an effort to develop effective antiamoebic agents, some hydrazones and azoles containing pyridyl moiety were synthesized and screened for in vitro antiamoebic activity against HM1:IMSS strain of Entamoeba histolytica. Among all the compounds, only five compounds (1, 3, 5, 9 and 11) were found to be better inhibitors of growth of E. histolytica than the reference drug metronidazole. The cytotoxic studies of these compounds on human breast cancer MCF-7 cell line revealed that all the compounds were low-cytotoxic in the concentration range of 2.5-250 MUM. PMID- 22309915 TI - New heterocyclic compounds from 1,2,4-triazole and 1,3,4-thiadiazole class bearing diphenylsulfone moieties. Synthesis, characterization and antimicrobial activity evaluation. AB - Some new 5-(4-(4-X-phenylsulfonyl)phenyl)-4-(R)-2H-1,2,4-triazol-3(4H)-thiones 4a,b; 5a,b and 5-(4-(4-X-phenylsulfonyl)phenyl)-N-(R)-1,3,4-thiadiazol-2-amines 6a,b; 7a,b were obtained by cyclization of new N(1)-[4-(4-X phenylsulfonyl)benzoyl]-N(4)-(R)-thiosemicarbazides 2a,b; 3a,b (X=H, Br). The 1,2,4-triazoles were synthesized by intramolecular cyclization of acylthiosemicarbazides, in basic media. On the other hand, 1,3,4-thiadiazoles were obtained from same acylthiosemicarbazides, in acidic media. These new intermediates from thiosemicarbazide class were afforded by the reaction of 4-(4 X-phenylsulfonyl)benzoic acids hydrazides (X=H, Br) 1a,b with 4 trifluoromethoxyphenyl or 3,4,5-trimethoxyphenyl isothiocyanate. The newly synthesized compounds were characterized by IR, (1)H NMR, (13)C NMR, MS and elemental analysis. All the new compounds were screened for their antimicrobial activity against some bacteria (Staphylococcus aureus ATCC 25923, Bacillus cereus ATCC 13061, Escherichia coli ATCC 25922, Enterobacter cloacae ATCC 49141, Acinetobacter baumannii ATCC 19606 and Pseudomonas aeruginosa ATCC 27853) and yeasts (Candida albicans ATCC 90028 and Candida parapsilosis ATCC 22019). PMID- 22309916 TI - Antiproliferative activity against human non-small cell lung cancer of two O alkyl-diglycosylglycerols from the marine sponges Myrmekioderma dendyi and Trikentrion laeve. AB - Glycolipids of Myrmekioderma sponges contain Myrmekiosides, a new family of glycolipids with a unique structure of mono-O-alkyl-diglycosylglycerols. This report deals with the identification and biological activity of the new Myrmekioside E from Myrmekioderma dendyi. Its structure has been elucidated from spectroscopic data and chemical degradation studies. It contained a glycerol backbone linked to xylose and N-acetylglucosamine, and an alkyl long-chain with a terminal alcohol group. A related glycolipid, Trikentroside, known in the sponge Trikentrion laeve, was subjected to a comparative biological evaluation. Both glycolipids inhibit proliferation of two human non-small cell lung cancer cell lines (NSCLC-N6 and A549). PMID- 22309919 TI - Growth of the dental hygiene profession. PMID- 22309920 TI - Current topics in oral cancer research and oral cancer screening. PMID- 22309921 TI - The state of the science of lasers in dentistry. PMID- 22309922 TI - An introduction to grant writing: de-mystifying the process. PMID- 22309923 TI - Techniques for professional presentation of scientific information. PMID- 22309924 TI - Writing for publication in scientific journals. PMID- 22309925 TI - Keeping current: clinical decision support systems. PMID- 22309926 TI - Overcoming the fear of statistics: survival skills for researchers. PMID- 22309927 TI - Getting started in clinical research. PMID- 22309928 TI - Introduction to preparing a systematic review. PMID- 22309929 TI - Design considerations for qualitative research: getting at strawberry milk. PMID- 22309930 TI - Osteonecrosis of the jaw and oral hygiene: a case-control study from Condor Dental PBRN. PMID- 22309931 TI - Dental practice implementation of a point of care electronic referral system for patients who smoke: a dental PBRN study. PMID- 22309932 TI - Current evidence for remineralizing therapeutics in caries management. PMID- 22309933 TI - CAMBRA: development and incorporation into a dental hygiene program. PMID- 22309934 TI - Feasibility and efficacy of bypassing the right ventricle and pulmonary circulation to treat right ventricular failure: an experimental study. AB - BACKGROUND: Right ventricular failure (RVF) and -support is associated with poor results. We aimed for a new approach of right - sided assistance bypassing the right ventricle and pulmonary circulation in order to better decompress the right ventricle and optimize left ventricular filling. METHODS: From a microaxial pump (Abiomed), a low resistance oxygenator (Maquet and Novalung) and two cannulas (28 and 27 Fr) a system was set up and evaluated in an ovine model (n = 7). Connection with the heart was the right and left atrium. One hour the system was operated without RVF and turned of again. Then a RVF was induced and the course with the system running was evaluated. Complete hemodynamic monitoring was performed as well as echocardiography, flow measurement and blood gas analysis. RESULTS: The overall performance of the system was reliable. Without RVF no relevant changes of hemodynamics occurred; blood gases were supra normal. In RVF a cardiogenic shock developed (MAP 35 +/- 13 mmHg, CO 1,1 +/- 0,7 l/min). Immediately after starting the system the circulation normalized (significant increase of MAP to 85 +/- 13 mmHg, of CO to 4,5 +/- 1,9). Echocardiography also revealed right ventricular recovery. After stopping the system, RVF returned. CONCLUSIONS: Bypassing the right ventricle and pulmonary circulation with an oxygenating assist device, which may offer the advantages of enhanced right ventricular decompression and augmented left atrial filling, is feasible and effective in the treatment of acute RVF. Long time experiments are needed. PMID- 22309935 TI - Effect of vaccination against gonadotrophin-releasing factor on growth performance, carcass, meat and fat quality of male Duroc pigs for dry-cured ham production. AB - The aim of this study was to compare production, carcass and meat quality parameters, boar taint compounds and fat composition of green and dry-cured hams, between immunocastrated (IM), surgically castrated (CM) and female (FE) Duroc purebred pigs (n=75, 138.7+/-8.27kg). Liveweight and fat and muscle thicknesses were measured and average daily gain was calculated during growth. Carcass, meat and fat quality parameters were measured. Immunocastrated grew faster than CM or FE after the second dose of vaccine. IM had the lowest dressing percentage but similar % of ham and carcass lean to FE and CM. The effect of the immunocastration on carcass fatness depended on the location, did not affect fat and meat quality and reduced skatole and androstenone levels. Both in green and dry-cured ham, immunocastration slightly altered FA composition. Thus, Duroc pigs vaccinated with Improvac are suitable for the production of high quality dry cured ham. PMID- 22309936 TI - "How did you feel?": increasing child sexual abuse witnesses' production of evaluative information. AB - In child sexual abuse cases, the victim's testimony is essential, because the victim and the perpetrator tend to be the only eyewitnesses to the crime. A potentially important component of an abuse report is the child's subjective reactions to the abuse. Attorneys may ask suggestive questions or avoid questioning children about their reactions, assuming that children, given their immaturity and reluctance, are incapable of articulation. We hypothesized that How questions referencing reactions to abuse (e.g., "how did you feel") would increase the productivity of children's descriptions of abuse reactions. Two studies compared the extent to which children provided evaluative content, defined as descriptions of emotional, cognitive, and physical reactions, in response to different question-types, including How questions, Wh- questions, Option-posing questions (yes-no or forced-choice), and Suggestive questions. The first study examined children's testimony (ages 5-18) in 80 felony child sexual abuse cases. How questions were more productive yet the least prevalent, and Option-posing and Suggestive questions were less productive but the most common. The second study examined interview transcripts of 61 children (ages 6-12) suspected of being abused, in which children were systematically asked How questions regarding their reactions to abuse, thus controlling for the possibility that in the first study, attorneys selectively asked How questions of more articulate children. Again, How questions were most productive in eliciting evaluative content. The results suggest that interviewers and attorneys interested in eliciting evaluative reactions should ask children "how did you feel?" rather than more direct or suggestive questions. PMID- 22309937 TI - Probing transient Hoogsteen hydrogen bonds in canonical duplex DNA using NMR relaxation dispersion and single-atom substitution. AB - Nucleic acids transiently morph into alternative conformations that can be difficult to characterize at the atomic level by conventional methods because they exist for too little time and in too little abundance. We recently reported evidence for transient Hoogsteen (HG) base pairs in canonical B-DNA based on NMR carbon relaxation dispersion. While the carbon chemical shifts measured for the transient state were consistent with a syn orientation for the purine base, as expected for A(syn)*T(anti) and G(syn)*C(+)(anti) HG base pairing, HG type hydrogen bonding could only be inferred indirectly. Here, we develop two independent approaches for directly probing transient changes in N-H...N hydrogen bonds and apply them to the characterization of transient Hoogsteen type hydrogen bonds in canonical duplex DNA. The first approach takes advantage of the strong dependence of the imino nitrogen chemical shift on hydrogen bonding and involves measurement of R(1rho) relaxation dispersion for the hydrogen-bond donor imino nitrogens in G and T residues. In the second approach, we assess the consequence of substituting the hydrogen-bond acceptor nitrogen (N7) with a carbon (C7H7) on both carbon and nitrogen relaxation dispersion data. Together, these data allow us to obtain direct evidence for transient Hoogsteen base pairs that are stabilized by N-H...N type hydrogen bonds in canonical duplex DNA. The methods introduced here greatly expand the utility of NMR in the structural characterization of transient states in nucleic acids. PMID- 22309938 TI - Differential response of oxidative stress and thiol metabolism in contrasting rice genotypes for arsenic tolerance. AB - The mechanism of arsenic (As) tolerance was investigated on two contrasting rice (Oryza sativa L.) genotypes, selected for As tolerance and accumulation. One tolerant (Triguna) and one sensitive (IET-4786) variety were exposed to various arsenate (0-50 MUM) levels for 7 d for biochemical analyses. Arsenic induced oxidative stress was more pronounced in IET-4786 than Triguna especially in terms of reactive oxygen species, lipid peroxidation, EC and pro-oxidant enzymes (NADPH oxidase and ascorbate oxidase). However, Triguna tolerated As stress through the enhanced enzymes activities particularly pertaining to thiol metabolism such as serine acetyl transferase (SAT), cysteine synthase (CS), gamma-glutamyl cysteine synthase (gamma-ECS), gamma-glutamyl transpeptidase (gamma-GT), and glutathione-S transferase (GST) as well as arsenate reductase (AR). Besides maintaining the ratio of redox couples GSH/GSSG and ASC/DHA, the level of phytochelatins (PCs) and phytochelatin synthase (PCS) activity were more pronounced in Triguna, in which harmonized responses of thiol metabolism was responsible for As tolerance in contrast to IET-4786 showing its susceptible nature towards As exposure. PMID- 22309939 TI - Small interfering RNA library screen identified polo-like kinase-1 (PLK1) as a potential therapeutic target for breast cancer that uniquely eliminates tumor initiating cells. AB - INTRODUCTION: Triple-negative breast cancer (TNBC) high rate of relapse is thought to be due to the presence of tumor-initiating cells (TICs), molecularly defined as being CD44high/CD24-/low. TICs are resilient to chemotherapy and radiation. However, no currently accepted molecular target exists against TNBC and, moreover, TICs. Therefore, we sought the identification of kinase targets that inhibit TNBC growth and eliminate TICs. METHODS: A genome-wide human kinase small interfering RNA (siRNA) library (691 kinases) was screened against the TNBC cell line SUM149 for growth inhibition. Selected siRNAs were then tested on four different breast cancer cell lines to confirm the spectrum of activity. Their effect on the CD44high subpopulation and sorted CD44high/CD24-/low cells of SUM149 also was studied. Further studies were focused on polo-like kinase 1 (PLK1), including its expression in breast cancer cell lines, effect on the CD44high/CD24-/low TIC subpopulation, growth inhibition, mammosphere formation, and apoptosis, as well as the activity of the PLK1 inhibitor, BI 2536. RESULTS: Of the 85 kinases identified in the screen, 28 of them were further silenced by siRNAs on MDA-MB-231 (TNBC), BT474-M1 (ER+/HER2+, a metastatic variant), and HR5 (ER+/HER2+, a trastuzumab-resistant model) cells and showed a broad spectrum of growth inhibition. Importantly, 12 of 28 kinases also reduced the CD44high subpopulation compared with control in SUM149. Further tests of these 12 kinases directly on a sorted CD44high/CD24-/low TIC subpopulation of SUM149 cells confirmed their effect. Blocking PLK1 had the greatest growth inhibition on breast cancer cells and TICs by about 80% to 90% after 72 hours. PLK1 was universally expressed in breast cancer cell lines, representing all of the breast cancer subtypes, and was positively correlated to CD44. The PLK1 inhibitor BI 2536 showed similar effects on growth, mammosphere formation, and apoptosis as did PLK1 siRNAs. Finally, whereas paclitaxel, doxorubicin, and 5-fluorouracil enriched the CD44high/CD24-/low population compared with control in SUM149, subsequent treatment with BI 2536 killed the emergent population, suggesting that it could potentially be used to prevent relapse. CONCLUSION: Inhibiting PLK1 with siRNA or BI 2536 blocked growth of TNBCs including the CD44high/CD24-/low TIC subpopulation and mammosphere formation. Thus, PLK1 could be a potential therapeutic target for the treatment of TNBC as well as other subtypes of breast cancer. PMID- 22309940 TI - Analysis of N(epsilon) -ethyllysine in human plasma proteins by gas chromatography-negative ion chemical ionization/mass spectrometry as a biomarker for exposure to acetaldehyde and alcohol. AB - BACKGROUND: N(epsilon) -ethyllysine (NEL) is a major stable adduct formed by the reaction of acetaldehyde (AA) with lysine residues in proteins. However, its occurrence and levels in biological specimens and its relationship with AA/alcohol exposure-associated disorders have not been fully elucidated. In this study, we have developed a sensitive and specific method to quantitate NEL levels in human plasma proteins. METHODS: The method consists of (1) purification of the protein fraction of interest by Sephadex G-15 to remove low molecular substances, (2) hydrolysis of proteins with Pronase E in the presence of stable isotope labeled internal standards, (3) derivatization of amino acids with pentafluorobenzyl (PFB) bromide, and (4) quantification of the PFB derivatives of NEL and l-lysine using gas chromatography-negative ion chemical ionization/mass spectrometry in a selected ion monitoring mode. RESULTS: Using the above method, the NEL levels in human plasma proteins obtained from 10 each of control subjects and alcoholic patients were measured. NEL was detected in all samples analyzed, the average level of NEL in the plasma proteins of alcoholic patients (1.17 +/- 0.36 NEL/1,000 l-lysine) being significantly higher than that of control subjects (0.26 +/- 0.07 NEL/1,000 l-lysine). CONCLUSIONS: The method could be applied to molecular epidemiological studies to investigate possible associations between the NEL levels in human tissue proteins and human diseases associated with exposure to AA and alcohol. PMID- 22309941 TI - Basic fibroblast growth factor suppresses meiosis and promotes mitosis of ovarian germ cells in embryonic chickens. AB - Basic fibroblast growth factor (bFGF or FGF2) plays diverse roles in regulating cell proliferation, migration and differentiation during embryo development. In this study, the effect of bFGF on ovarian germ cell development was investigated in the embryonic chicken by in vitro and in vivo experiments. Results showed that a remarkable decrease in bFGF expression in the ovarian cortex was manifested during meiosis progression. With ovary organ culture, we revealed that meiosis was initiated after retinoic acid (RA) treatment alone but was decreased after combined bFGF treatment that was detected by real time RT-PCR, fluorescence immunohistochemistry and Giemsa staining. Further, no significant difference in mRNA expression of either RA metabolism-related enzymes (Raldh2 and Cyp26b1) or RA receptors was displayed after bFGF challenge. This result suggests that the suppression of bFGF on meiosis was unlikely through inhibition of RA signaling. In addition, as a mitogen, bFGF administration increased germ cell proliferation (via BrdU incorporation) in cultured organ or cells in vitro and also in developing embryos in vivo. In contrast, blockade of bFGF action by SU5402 (an FGFR1 antagonist) or inhibition of protein kinase C signaling showed inhibited effect of bFGF on mitosis. In conclusion, bFGF suppresses RA-induced entry of germ cells into meiosis to ensure embryonic ovarian germ cells to maintain at undifferentiated status and accelerate germ cell proliferation by binding with FGFR1 involving PKC activation in the chicken. PMID- 22309942 TI - Changes in the small intestine of Schistosoma mansoni-infected mice fed a high fat diet. AB - The consumption of a high-fat diet modifies both the morphology of the small intestine and experimentally tested effects of schistosomiasis mansoni. However, whether a schistosomiasis infection associated with a high-fat diet causes injury to the small intestine has never been investigated. Mice were fed either a high fat or a standard-fat diet for 6 months and were then infected with Schistosoma mansoni cercariae. Physical characteristics of the intestinal tissue (mucosal thickness, small intestinal villi length and height, and abundance of goblet cells and enterocytes on the villous surface) and the distribution of granulomas along the intestinal segments and their developmental stage were measured at the time of sacrifice (9 or 17 weeks post-infection). The group fed a high-fat diet exhibited different granuloma stages, whereas the control group possessed only exudative granulomas. The chronically infected mice fed a high-fat diet exhibited higher granuloma and egg numbers than the acutely infected group. Exudative, exudative/exudative-productive and exudative-productive granulomas were present irrespective of diet. Computer-aided morphometric analysis confirmed that villus length, villus width, muscular height and submucosal height of the duodenal and jejunal segments were affected by diet and infection. In conclusion, a high-fat diet and infection had a significant impact on the small intestine morphology and morphometry among the animals tested. PMID- 22309943 TI - Golgi apparatus: Homotypic fusion maintains biochemical gradients within the Golgi and improves the accuracy of protein maturation. AB - Eukaryotic cells are compartmentalized into organelles which, although constantly exchanging proteins and lipids with their environment, maintain a relatively well defined biochemical identity. How can such large heterogeneities of chemical composition between (and within) organelles be maintained if different organelles are in constant contact through mass transport? Generic nonlinearities in the transport processes, as would result from specific molecular interactions, can cause the spontaneous chemical differentiation of interacting organelles and compartments within organelles. For the Golgi apparatus, the role of which is to process an incoming flux of lipids and proteins, this spontaneous differentiation decreases inter-cisternal exchange and increases the protein transit time under conditions of high incoming flux, This mechanism enables the Golgi apparatus to spontaneously adjust the protein transit time to the amount of protein requiring processing, thereby improving the processing accuracy of even a limited amount of maturation enzymes. PMID- 22309944 TI - Glioma derived isocitrate dehydrogenase-2 mutations induced up-regulation of HIF 1alpha and beta-catenin signaling: possible impact on glioma cell metastasis and chemo-resistance. AB - The identification of heterozygous mutations (with an incidence up to 85%) in either the R132 residue of isocitrate dehydrogenase-1 (IDH1) or the R172 residue of IDH2 in human low-grade diffuse gliomas was remarkable because no oncogenic pathway had been previously documented correlated with these enzymes. In spite of a recent surge in elucidating the tumorigenic activity of IDH mutations in glioblastoma, the underlying biological mechanisms remain poorly understood. We showed here that C6 glioma cells transiently over-expressing IDH2(R172G) induced nuclear accumulation of beta-catenin, up-regulation of HIF-1alpha signaling and corresponding proteins expression that were closely related with tumor invasion and chemo-resistance. These results demonstrated a functional model in which IDH mutations were closely interrelated with glioma progression and could hold some therapeutic implications for future human glioma treatment. PMID- 22309945 TI - Does flexibility in perceptual organization compete with automatic grouping? AB - Segregated objects can be sought simultaneously, i.e., mentally "re-grouped." Although the mechanisms underlying such "re-grouping" clearly differ from automatic grouping, it is unclear whether or not the end products of "re grouping" and automatic grouping are the same. If they are, they would have similar impact on visual organization but would be in conflict. We compared the consequences of grouping and re-grouping on the performance cost induced by stimuli presented across hemifields. Two identical and contiguous target figures had to be identified within a display of circles and squares alternating around a fixation point. Eye tracking was used to check central fixation. The target pair could be located in the same or separate hemifields. A large cost of presenting targets across hemifields was observed. Grouping by connectedness yielded two types of target pair, connected and unconnected. Subjects prioritized unconnected pairs efficiently when prompted to do so, suggesting "re-grouping." However, unlike automatic grouping, this did not affect the cost of across-hemifield presentation. The suggestion is that re-grouping yields different outputs to automatic grouping, such that a fresh representation resulting from re-grouping complements the one resulting from automatic grouping but does not replace it. This is one step toward understanding how our mental exploration of the world ties in and coexists with ongoing perception. PMID- 22309946 TI - Clinical performance and skill retention after simulation-based education for nephrology fellows. AB - We previously demonstrated that simulation-based education (SBE) improved temporary hemodialysis catheter (THDC) insertion skills by nephrology fellows. SBE, featuring deliberate practice and rigorous achievement standards, was a powerful method to enhance THDC insertion skills in nephrology fellows. However, experts have called for further research to evaluate skill transfer from the simulated environment to actual clinical care and skill retention. This is a prospective observational cohort study of THDC insertion skills. Twelve nephrology fellows from three academic centers in Chicago were evaluated using a skills checklist from July 2008 to June 2009. Simulator-trained fellows were tested after the SBE intervention and expected to meet or exceed a minimum passing score (MPS) set by an expert panel. To assess transfer of skill to clinical care, three simulator-trained fellows were assessed at 6 months on actual patient THDC insertions using the checklist. To assess retention of skill, 11 of 12 simulator-trained fellows were reassessed at 1 year using the checklist and central venous catheter simulator. Outcomes were determined by THDC insertion skill performance. Simulator-trained fellows scored similarly during 6-month THDC insertions on actual patients and immediate posttest (M = 86.2%, SD = 22.3% vs. M = 93.5%, SD = 5.3%, p = 0.32). However, 1 year after SBE, simulated THDC insertion scores were significantly lower than at immediate posttest (M = 73.4%, SD = 22.2% vs. M = 93.5%, SD = 5.3%, p = 0.01). Our results show that nephrology fellows who completed SBE displayed high levels of performance during THDC insertions on actual patients 6 months later. At 1 year, there was statistically significant skills decay. We recommend booster training at 6 months. PMID- 22309947 TI - Gender differences in quality of life among Canadian adults with epilepsy. AB - The clinical literature suggests epilepsy may impact quality of life in males and females differently. Previous research on gender issues has focused primarily on biological-biomedical factors over psychological and social factors. In this study we compare subjective and objective quality of life in adult persons with epilepsy to persons without epilepsy by gender using the biopsychosocial model in the Canadian Community Health Survey (CCHS), a large epidemiological survey that covers 98% of the Canadian population. Logistic regression analyses were conducted using self-rated health status and the Health Utility Index((r)) 3 (HUI3) as the outcomes. Quality of life was significantly moderated after controlling for the biological-biomedical variables in all analyses except the HUI3. Males with epilepsy were more likely to have HUI3 scores of 0.70 or greater than males without epilepsy (OR = 1.61, 95%CI 1.32-1.96). For males with epilepsy the HUI3 was further moderated, but remained significantly better in the final model that controlled for biological, psychological and social factors (OR = 1.43, 95%CI 1.17-1.76). Our findings provide support for treatment approaches that focus on the whole person. Such approaches should take into account gender differences when examining objective quality of life. PMID- 22309948 TI - First description of unilateral lung agenesis and anomalous pulmonary venous connection in a newborn with Goldenhar syndrome. AB - We present a unique case of unilateral lung agenesis and anomalous pulmonary venous return in a newborn with Goldenhar syndrome. PMID- 22309949 TI - Multilevel predictors of adolescent physical activity: a longitudinal analysis. AB - BACKGROUND: To examine how factors from a social ecologic model predict physical activity (PA) among adolescents using a longitudinal analysis. METHODS: Participants in this longitudinal study were adolescents (ages 10-16 at baseline) and one parent enrolled in the Transdisciplinary Research on Energetics and Cancer-Identifying Determinants of Eating and Activity (TREC-IDEA) and the Etiology of Childhood Obesity (ECHO). Both studies were designed to assess a socio-ecologic model of adolescent obesity risk. PA was collected using ActiGraph activity monitors at two time points 24 months apart. Other measures included objective height and weight, adolescent and parent questionnaires on multilevel psychological, behavioral and social determinants of PA, and a home PA equipment inventory. Analysis was conducted using SAS, including descriptive characteristics, bivariate and stepped multivariate mixed models, using baseline adjustment. Models were stratified by gender. RESULTS: There were 578 adolescents with complete data. Results suggest few statistically significant longitudinal associations with physical activity measured as minutes of MVPA or total counts from accelerometers. For boys, greater self-efficacy (B = 0.75, p = 0.01) and baseline MVPA (B = 0.55, p < 0.01) remained significantly associated with MVPA at follow-up. A similar pattern was observed for total counts. For girls, baseline MVPA (B = 0.58, p = 0.01) and barriers (B = -0.32, p = 0.05) significantly predicted MVPA at follow-up in the full model. The full multilevel model explained 30% of the variance in PA among boys and 24% among girls. CONCLUSIONS: PA change in adolescents is a complex issue that is not easily understood. Our findings suggest early PA habits are the most important predictor of PA levels in adolescence. Intervention may be necessary prior to middle school to maintain PA through adolescence. PMID- 22309950 TI - Elevated antilysosomal-associated membrane protein-2 antibody levels in patients with adult Henoch-Schonlein purpura. AB - BACKGROUND: Henoch-Schonlein purpura (HSP) is characterized by IgA-containing immune complexes within leucocytoclastic vasculitis. Lysosomal-associated membrane protein-2 (LAMP-2) was first identified as part of a systematic search for antineutrophil cytoplasmic antibody (ANCA) antigens expressed on neutrophils and endothelial cells. OBJECTIVES: To investigate the presence of ANCA in patients with adult HSP and microscopic polyangiitis (MPA), and to measure serum LAMP-2 antibody levels in these patients. METHODS: Twenty-four adult patients with HSP, eight with MPA and 24 normal healthy controls were examined. ANCA detection was performed using indirect immunofluorescence (IIF), a direct enzyme linked immunosorbent assay (ELISA) and a capture ELISA specific for myeloperoxidase (MPO) and proteinase 3 (PR3). We measured other ANCA-associated antibodies including anti-LAMP-2 antibody in serum using ELISA. Immunohistochemical (IHC) staining was used for anti-LAMP-2 antibody expression in patient skin biopsies. To determine the cut-off value of the serum anti-LAMP-2 antibody, a receiver operating characteristic (ROC) curve was constructed using statistical analysis software (JMP 8.0.2; SAS Institute Inc., Cary, NC, U.S.A.). RESULTS: The sera of all patients with HSP were negative for MPO-ANCA and PR3 ANCA by direct ELISA and by capture ELISA. However, ANCA was present in 17 (71%) of the 24 patients with HSP based on IIF. In contrast, we found MPO-ANCA in all eight patients with MPA using both ELISA methods. We found serum anti-LAMP-2 antibody levels in HSP significantly higher than in MPA and in healthy individuals (P = 0.002 and P = 0.00167, respectively). The area under the curve of serum anti-LAMP-2 antibody between HSP and MPA was 0.8698 by ROC analysis. The optimal cut-off point was 0.267 U mL(-1) (sensitivity 1.000, specificity 0.583). We found a significant positive correlation between serum anti-LAMP-2 antibody levels and serum IgA levels in HSP (r(s) = 0.731, P = 0.00226). Anti-LAMP-2 antibody overexpression in IHC staining was present in 20 (83%) of the patients with HSP. The overexpression was observed within the neutrophils and endothelial cells of leucocytoclastic vasculitis. There was a significant positive correlation between IHC staining score and positive serum anti-LAMP-2 antibody. The 24 patients with HSP and the eight patients with MPA were negative for antiazurocidin antibodies, antibactericidal permeability increasing protein antibodies, anticathepsin G antibodies, antielastase antibodies, antilactoferrin antibodies and antilysozyme antibodies. CONCLUSIONS: We suggest that anti-LAMP-2 antibody could play some role in the pathogenesis of adult HSP, and have excluded a role for MPO-ANCA and PR3-ANCA. We propose that measuring serum anti-LAMP-2 antibody could be a feasible method of differential diagnosis between HSP and MPA. PMID- 22309951 TI - 25-Hydroxycholecalciferol status in plasma is linearly correlated to daily summer pasture time in cattle at 56 degrees N. AB - In vitro studies with skin samples or pure precursors of cholecalciferol indicated that cholecalciferol synthesis during UV light exposure is a non-linear process. However, in vitro studies indicate nothing about the relationship between sunlight exposure and physiological cholecalciferol status of living organisms. Due to the lack of cholecalciferol in plant material, this relationship is important for herbivores including domestic cattle, particularly in organic agriculture, because the use of synthetic additives, like cholecalciferol, is restricted in order to fulfil the principles of sustainable organic production. The major physiological metabolite of cholecalciferol is the liver-derived 25-hydroxycholecalciferol (25(OH)D3). The purpose of the present study was to determine the relationship between sunlight exposure and 25(OH)D3 status in vivo in large herbivores during mid-summer at 56 degrees N. Five groups of cows were given access to pasture during 15, 30, 75, 150 or 300 min daily for 28 d in June and plasma analysed for 25(OH)D3. Animals allowed 15, 30 or 75 min of daily access to pasture showed a declining linear relationship between plasma 25(OH)D3 and sampling day in contrast to animals allowed 150 or 300 min of pasture access which showed linear increasing plasma 25(OH)D3 status. Determined from the slopes of 25(OH)D3 concentration curves within treatments, breakeven for maintaining the initial 25(OH)D3 status of 45 nmol/l was 90 min pasture access per d during summer at 56 degrees N. PMID- 22309952 TI - A comparison of different concentration methods for the detection of viruses present in bottled waters and those adsorbed to water bottle surfaces. AB - This study aimed to provide a tool for selecting the best approach to virological testing of bottled waters. Different methods were investigated. Method A examined the recovery of virus RNA following in situ lysis of virus particles in the aqueous phase and of those adhered to the bottle wall, method B examined the recovery of virus RNA following lysis of virus particles in the aqueous phase, and method C examined the recovery of intact virus particles. Method C generated the lowest genome recovery rate regardless of the water and virus type used, therefore comparison was mainly conducted between methods A and B.The effects of independent variables on the viral RNA recovery rate were determined by full factorial design. These independent variables included three waters (differing in mineral composition), four viruses (poliovirus 1, hepatitis A virus, Norovirus, and the MS2 phage), three incubation times (0, 10, and 20 days), and two methods (A and B). According to the results, each factor influenced the recovery rate of viral RNA with the exception of incubation time. Statistical analysis identified interactions between the factors. The strongest interactions involved the water and virus types, as well as the methods. The results suggested that method A should be used for the concentration and detection of hepatitis A virus, regardless of the divalent cation concentration of the bottled water. Method A was most suitable for water with the highest mineral content (divalent cation concentration of 250 mgL(-1)) and for the analysis of viruses capable of adsorbing onto the bottle walls (Poliovirus 1). Method B could be recommended for the analysis of water whose cation concentration is unknown. PMID- 22309954 TI - Animal type melanoma: an unusual case with aggressive histological features? AB - Animal-type melanoma (ATM) refers to a well-known but rare, heavily pigmented melanocytic tumor, considered a variant of malignant melanoma, the biological behavior and prognostic significance of which still remain to be completely established. We report a case characterized by proliferation of hyperpigmented epithelioid and spindle cells, focally ulcerating the epidermis. Tumor necrosis, perineural and vascular invasion, as well as a slightly high mitotic index, were also observed. Although there were several features indicating poor prognosis, the lesion was diagnosed as ATM and not as classical melanoma. This almost unique case could help us to confirm the excellent biological behavior of this "uncertain malignant potential tumor", suggesting a biological nature of ATM possibly different from classical melanoma, as reported in other molecular studies. In addition, the first rapid impression of aggressive melanoma could lead the pathologist to render an immediate, incorrect diagnosis. PMID- 22309953 TI - A unique case of synchronous functional adrenocortical adenoma and myelolipoma within the ectopic adrenal cortex in a child with Beckwith-Wiedemann syndrome. AB - We report a unique case of synchronous functional adrenocortical adenoma and an incidental myelolipoma within ectopic cortical adrenal tissue located in the renal hilum in a child with Beckwith-Wiedemann syndrome and review the association between adrenal gland disorders and myelolipomas. To the best of our knowledge, this is the first documented case of a simultaneous occurrence of these three conditions. A 17-month-old child with Beckwith-Wiedemann syndrome was diagnosed with a left adrenal tumor during complementary radiologic studies. Biochemical investigation before surgery showed elevated blood levels of cortisol and dehydroepiandrosterone hormones. The patient underwent a left adrenalectomy with ipsilateral renal hilar and intercaval-aortic lymph node dissection. Pathology findings revealed a left adrenocortical adenoma and an incidental myelolipoma growing within ectopic cortical adrenal tissue in the renal hilum. The patient is doing well and does not have any current health issues. Patients with adrenal cortex disorders, such as hyperplasias and neoplasms, particularly when associated with hormonal imbalances, may have an increased risk of developing myelolipomas. Whether Beckwith-Wiedemann syndrome may, by itself, contribute to simultaneous occurrence of adrenocortical adenomas and myelolipomas remains to be clarified. PMID- 22309955 TI - How to measure diversity when you must. AB - Racial/ethnic diversity has become an increasingly important variable in the social sciences. Research from multiple disciplines consistently demonstrates the tremendous impact of ethnic diversity on individuals and organizations. Investigators use a variety of measures, and their choices can affect the conclusions that can be drawn and limit the ability to compare and generalize results across studies effectively. The current article reviews 3 popular approaches to the measurement of diversity: the simplistic majority-minority approach and 2 multiple categories variants, the generalized variance and the lesser used entropy statistic. We discuss the properties of each approach and reject the majority-minority approach. We provide 5 examples using the generalized variance and entropy statistics and illustrate their versatility and flexibility. We urge investigators to adopt these multicategory measures and to use our discussion to determine which measure of diversity is most appropriate given the nature of one's data set and research question. PMID- 22309956 TI - Multilevel factorial experiments for developing behavioral interventions: power, sample size, and resource considerations. AB - Factorial experimental designs have many potential advantages for behavioral scientists. For example, such designs may be useful in building more potent interventions by helping investigators to screen several candidate intervention components simultaneously and to decide which are likely to offer greater benefit before evaluating the intervention as a whole. However, sample size and power considerations may challenge investigators attempting to apply such designs, especially when the population of interest is multilevel (e.g., when students are nested within schools, or when employees are nested within organizations). In this article, we examine the feasibility of factorial experimental designs with multiple factors in a multilevel, clustered setting (i.e., of multilevel, multifactor experiments). We conduct Monte Carlo simulations to demonstrate how design elements-such as the number of clusters, the number of lower-level units, and the intraclass correlation-affect power. Our results suggest that multilevel, multifactor experiments are feasible for factor-screening purposes because of the economical properties of complete and fractional factorial experimental designs. We also discuss resources for sample size planning and power estimation for multilevel factorial experiments. These results are discussed from a resource management perspective, in which the goal is to choose a design that maximizes the scientific benefit using the resources available for an investigation. PMID- 22309957 TI - Model selection and psychological theory: a discussion of the differences between the Akaike information criterion (AIC) and the Bayesian information criterion (BIC). AB - This article reviews the Akaike information criterion (AIC) and the Bayesian information criterion (BIC) in model selection and the appraisal of psychological theory. The focus is on latent variable models, given their growing use in theory testing and construction. Theoretical statistical results in regression are discussed, and more important issues are illustrated with novel simulations involving latent variable models including factor analysis, latent profile analysis, and factor mixture models. Asymptotically, the BIC is consistent, in that it will select the true model if, among other assumptions, the true model is among the candidate models considered. The AIC is not consistent under these circumstances. When the true model is not in the candidate model set the AIC is efficient, in that it will asymptotically choose whichever model minimizes the mean squared error of prediction/estimation. The BIC is not efficient under these circumstances. Unlike the BIC, the AIC also has a minimax property, in that it can minimize the maximum possible risk in finite sample sizes. In sum, the AIC and BIC have quite different properties that require different assumptions, and applied researchers and methodologists alike will benefit from improved understanding of the asymptotic and finite-sample behavior of these criteria. The ultimate decision to use the AIC or BIC depends on many factors, including the loss function employed, the study's methodological design, the substantive research question, and the notion of a true model and its applicability to the study at hand. PMID- 22309958 TI - A comparison of four approaches to account for method effects in latent state trait analyses. AB - Latent state-trait (LST) analysis is frequently applied in psychological research to determine the degree to which observed scores reflect stable person-specific effects, effects of situations and/or person-situation interactions, and random measurement error. Most LST applications use multiple repeatedly measured observed variables as indicators of latent trait and latent state residual factors. In practice, such indicators often show shared indicator-specific (or method) variance over time. In this article, the authors compare 4 approaches to account for such method effects in LST models and discuss the strengths and weaknesses of each approach based on theoretical considerations, simulations, and applications to actual data sets. The simulation study revealed that the LST model with indicator-specific traits (Eid, 1996) and the LST model with M - 1 correlated method factors (Eid, Schneider, & Schwenkmezger, 1999) performed well, whereas the model with M orthogonal method factors used in the early work of Steyer, Ferring, and Schmitt (1992) and the correlated uniqueness approach (Kenny, 1976) showed limitations under conditions of either low or high method specificity. Recommendations for the choice of an appropriate model are provided. PMID- 22309959 TI - A novel infusible botanically-derived drug, PG2, for cancer-related fatigue: a phase II double-blind, randomized placebo-controlled study. AB - PURPOSE: This study investigated the efficacy of the botanical-derived drug, PG2, a partially purified extract of Astragalus membranaceus, as a complementary and palliative medicine for managing cancer-related fatigue (CRF). METHODS: Patients with advanced cancer and moderate to severe CRF were randomized to receive either PG2 or a placebo (normal saline, NS) in the first treatment cycle (four weeks) in a double-blind manner; thereafter, on the next cycle (four weeks), all patients received open-label treatment with PG2. RESULTS: PG2 significantly improved CRF in the NS-primed group. In the first four week cycle, PG2 administration resulted in a greater fatigue-improvement response rate than seen with NS alone. In addition, approximately 82% of patients who reported an improvement of fatigue symptoms following the first cycle of PG2 experienced sustained benefits after administration of the second treatment cycle. Among patients treated with PG2 who did not report an improvement in symptoms throughout the first treatment cycle, approximately 71% showed significant improvement after the second treatment cycle. No major or irreversible toxicities were observed with PG2 treatment. CONCLUSION: PG2 might be an effective and safe treatment for relieving CRF among advanced cancer patients. PMID- 22309960 TI - The value of P wave dispersion in predicting reperfusion and infarct related artery patency in acute anterior myocardial infarction. AB - PURPOSE: The aim of this study is to investigate whether P wave dispersion (PWD), measured before, during and after fibrinolytic therapy (FT,) is able to predict successful reperfusion and infarct related artery (IRA) patency in patients with acute anterior MI who received FT. METHODS: Sixty-eight patients who presented with acute anterior MI were enrolled in the study. An electrocardiogram was performed before and at 30, 60, 90 and 120 minutes after the start of FT. PWD was defined as the difference between maximum and minimum P wave duration on standard 12-lead surface electrocardiogram. A multivariate logistic regression model was used to assess whether PWD was predictor of IRA patency and ST-segment resolution (STR) on electrocardiogram. RESULTS: PWD120 was significantly lower in patients with STR on electrocardiogram (38 patients) compared with those without STR (30 patients) (44.8+/-11.5 vs. 52.9+/-10.3 ms; p < 0.001). PWD120 was found to be significantly lower in patients with patent IRA (31 patients) compared to those with occluded IRA (37 patients) (42.3+/-9.7 vs. 53.5+/-10.6 ms; p < 0.001). Logistic regression analysis revealed that PWD120 significantly predicted STR and IRA patency. A >=51.6 ms PWD120 can predict an occluded IRA with a 87% sensitivity, >=51 ms PWD120 can predict no reperfusion with a 74% sensitivity. CONCLUSION: PWD values, which were higher than 51 ms and 51.6 ms in patients who received fibrinolytic therapy, can serve as a marker of failed reperfusion and occluded IRA. PWD values, in combination with other reperfusion parameters, can contribute to the identification of rescue PCI candidates. PMID- 22309961 TI - Lower plasma soluble TWEAK concentration in patients with newly diagnosed hypertension. AB - PURPOSE: To determine circulating levels of the soluble TNF-like weak inducer of apoptosis (sTWEAK)and its association with demographic and biochemical parameters in a young group of patients with newly diagnosed and never treated hypertension. METHODS: A total of 51 patients (mean age 21.7 +/-1.4 years, body mass index (BMI) 24.5 +/-1.6 kg/m2) with primary untreated hypertension, and 37 age- and BMI matched healthy controls (mean age 22.5 +/- 1.9 years, BMI 24.7 +/- 1.5 kg/m2) were studied. Serums TWEAK and plasma asymmetrical dimethyl arginine (ADMA) levels were measured by EIA. RESULTS: In patients and controls, mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 149.8+/-5.65/93.4+/ 3.4 mmHg and 124.2+/-6.4/78.24+/-5.5 mmHg, respectively. Serum sTWEAK levels were lower in the patient group (882.6+/-228.9 MUmol/L vs. 1060.2+/-231.7MUmol/L, p=0.001), whereas plasma ADMA levels were higher(0.837+/-0.34MUmol/L vs.0.3176+/ 0.25MUmol/L, p < 0.001). sTWEAK serum levels correlated with SBP(r=-0.301; p=0.005) and DBP (r=-0.279; p=0.009). Circulating plasma ADMA levels also correlated with SBP (r=0.734; p < 0.001) and DBP (r=0.733; p < 0.001). CONCLUSION: Young patients with yet untreated primary hypertension have lower circulating serum sTWEAK level compared with healthy controls. Further research for possible associations among serum sTWEAK, endothelial dysfunction and other measures of atherosclerosis may be of benefit in order to better understand the pathophysiology of hypertension and to establish more effective treatment options. PMID- 22309962 TI - Characterization of management and outcomes of patients with acromegaly in Vancouver over 30 years. AB - PURPOSE: The purpose of this study was to characterize the management and outcomes of patients with acromegaly seen in single center in Vancouver, British Columbia, Canada over a 30 year period. METHODS: The study involved retrospective data collection from charts of patients diagnosed with acromegaly since 1980: 130 patients (63 male and 67 female) were included in the analysis, with a mean age at diagnosis of 43 years (male) and 47 years (female). RESULTS: The most common presenting features included acral enlargement, coarse facial features, sweating/oily skin and headache. All cases were caused by pituitary adenomas, of which 58.5% were macroadenomas and of these, 30.8% were invasive. The most common co-morbidities were hypertension 31.5%, arthralgia 28%, diabetes 27.7% and sleep apnea 23.8%. The vast majority (88.5%) of patients was treated surgically and of these patients, 21.5% also received radiotherapy and 66.9% received medical therapy. When stringent cure criteria were applied (based on latest growth hormone (GH) and IGF-1 results) the outcomes were 35.4% cured or controlled, 30% remained active, 15.4 discordant results and 19.2 % with no results reported. Twenty eight percent of patients who underwent surgery and 32% of patients who underwent radiotherapy were not cured but symptoms were moderately well controlled with medical therapy. CONCLUSION: Based on the size of population studied, this study showed a prevalence of acromegaly of 29 per million. The cure rate was low following surgery but with adjuvant medical treatment disease control was achieved in most individuals. PMID- 22309963 TI - Increased expression of CD55 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma. AB - PURPOSE: To analyze the expression of complement delay-accelerating factor (CD55) in nasopharyngeal carcinoma and its correlation with clinicopathologic features, including survival rate. METHODS: Eighty-two nasopharyngeal carcinoma tissues were evaluated for CD55 expression using immunohistochemistry. The association between CD55 expression and various clinicopathological characteristics including overall survival was analyzed. RESULTS: Immunohistochemical analysis revealed that the protein expression of CD55 detected in nasopharyngeal carcinoma tissues was higher than that in the normal nasopharyngeal tissue (P=0.003). In addition, high levels of CD55 protein were positively correlated with the status of lymph node metastasis (P=0.02) and distant metastasis (P=0.01), and clinical stage (P=0.002) of nasopharyngeal carcinoma patients. Patients with positive CD55 expression had a significantly shorter overall survival time than did patients with negative CD55 expression (P=0.001). Multivariate analysis suggested that the expression pattern of CD55 protein was an independent prognostic indicator (P=0.009) for the survival of patients with nasopharyngeal carcinoma. CONCLUSION: The data from this study suggest, for the first time, that CD55 is frequently expressed in nasopharyngeal carcinoma and its expression is associated with decreased patient survival; therefore, CD55 expression may be a potential unfavorable prognostic factor for patients with nasopharyngeal carcinoma. PMID- 22309964 TI - Comparing health behaviours of internal medicine residents and medical students: an observational study. AB - PURPOSE: During residency, many physicians find it difficult to maintain a healthy lifestyle; however, there is little objective data available. In this study, residents' health behaviours and cardiovascular risk status were compared with those of medical students. METHODS: Medical residents (n=55, postgraduate years 1 to 4) were compared with medical students (n=62, years 1-4). The main dependent variable was the average number of steps per day (assessed using a pedometer) at work and leisure over three days, during which subjects were not on call or post-call. In addition, all subjects completed a three day food log. Frequency of vigorous exercise was assessed by a single question. Body mass index (BMI), waist circumference, blood pressure, total and high-density lipoprotein cholesterol, smoking habits and random blood glucose were measured, and Framingham Risk Score coronary artery disease 10 year probabilities (FRS) were calculated. RESULTS: Residents recorded 8344+/-3520 steps per day while students recorded 10703+/-3986 (p < 0.002). 35% of residents and 52% of students averaged more than 10,000 steps per day and senior residents took fewer steps than junior residents. Both groups frequently failed to achieve the recommended daily servings of fruits and vegetables; on average, 3.5+/-2.0 servings for residents and 5.4+/-2.2 for students (p < 0.0001). BMI and FRS were higher among the residents in comparison with the students. CONCLUSION: Medical residents at our institution appear less active and consume fewer servings of fruits and vegetables than undergraduate medical students. These differences are associated with higher BMI, waist circumference and cardiovascular risk. PMID- 22309965 TI - Natural and synthetic alpha-methylenelactones and alpha-methylenelactams with anticancer potential. AB - alpha-Methylene-gamma- and delta-lactones, as well as alpha-methylene-gamma- and delta-lactams, are plant-derived compounds often used in traditional medicine for the treatment of inflammatory diseases. In recent years, the anticancer properties of these compounds and the molecular mechanisms of their action have been studied extensively. In the search for modern anticancer drugs, various synthetic analogs of alpha-methylene-gamma- and delta-lactones and lactams have been synthesized and tested for their cytotoxic activity. In this review, we give a brief description of the occurrence and biological activity of such compounds isolated from plants and their diverse synthetic analogs. PMID- 22309966 TI - Optimization of oxygen delivery during high-risk surgery: keeping the concept but refining goals for inotrope infusion? PMID- 22309967 TI - Thrombotic microangiopathy: current knowledge and outcomes with plasma exchange. AB - The classification of thrombotic microangiopathy has evolved and expanded due to treatment and mechanistic advances. The two basic clinical forms of thrombotic microangiopathy (excluding disseminated intravascular coagulation [DIC]), thrombotic thrombocytopenic purpura (TTP), and hemolytic uremic syndrome (HUS) encompass a wide range of primary and secondary forms. The advent of plasma therapy and the identification of an inhibitor to ADAMTS13 in the idiopathic or acute forms of TTP and its absence in diarrheal HUS have had a major impact on our current classification of thrombotic microangiopathy. In adults, the difficulty of differentiating TTP, which is much more common than HUS and the need for a speedy diagnosis to provide life-saving plasma therapy has resulted in the term TTP/HUS for adult forms of thrombotic microangiopathy that present with unexplained thrombocytopenia and microangiopathic hemolytic anemia without a DIC. In this adult population a primary idiopathic and hereditary form as well as eight known secondary categories or clinical forms of TTP/HUS have been identified. HUS also embraces a primary (atypical HUS) and secondary forms (majority, diarrheal HUS secondary to Escherichia coli 0157:H7). In children, who present with HUS with no preceding history of diarrhea, plasma therapy is also offered on an urgent basis and studies are carried out to determine if they are suffering an abnormality in complement activation that may require eculizumab therapy. The advent of plasma therapy in the treatment of thrombotic microangiopathy has led to a clearer understanding of the role of ADAMTS13, both short- and long-term outcomes and the need for future surveillance and intervention. PMID- 22309968 TI - Collaborative evaluation and market research converge: an innovative model agricultural development program evaluation in Southern Sudan. AB - In June and July 2006 a team of outside experts arrived in Yei, Southern Sudan through an AID project to provide support to a local agricultural development project. The team brought evaluation, agricultural marketing and financial management expertise to the in-country partners looking at steps to rebuild the economy of the war ravaged region. A partnership of local officials, agricultural development staff, and students worked with the outside team to craft a survey of agricultural traders working between northern Uganda and Southern Sudan the steps approach of a collaborative model. The goal was to create a market directory of use to producers, government officials and others interested in stimulating agricultural trade. The directory of agricultural producers and distributors served as an agricultural development and promotion tool as did the collaborative process itself. PMID- 22309969 TI - de novo analysis and functional classification of the transcriptome of the root lesion nematode, Pratylenchus thornei, after 454 GS FLX sequencing. AB - The migratory endoparasitic root lesion nematode Pratylenchus thornei is a major pest of the cereals wheat and barley. In what we believe to be the first global transcriptome analysis for P. thornei, using Roche GS FLX sequencing, 787,275 reads were assembled into 34,312 contigs using two assembly programs, to yield 6,989 contigs common to both. These contigs were annotated, resulting in functional assignments for 3,048. Specific transcripts studied in more detail included carbohydrate active enzymes potentially involved in cell wall degradation, neuropeptides, putative plant nematode parasitism genes, and transcripts that could be secreted by the nematode. Transcripts for cell wall degrading enzymes were similar to bacterial genes, suggesting that they were acquired by horizontal gene transfer. Contigs matching 14 parasitism genes found in sedentary endoparasitic nematodes were identified. These genes are thought to function in suppression of host defenses and in feeding site development, but their function in P. thornei may differ. Comparison of the common contigs from P. thornei with other nematodes showed that 2,039 were common to sequences of the Heteroderidae, 1,947 to the Meloidogynidae, 1,218 to Radopholus similis, 1,209 matched expressed sequence tags (ESTs) of Pratylenchus penetrans and Pratylenchus vulnus, and 2,940 to contigs of Pratylenchus coffeae. There were 2,014 contigs common to Caenarhabditis elegans, with 15.9% being common to all three groups. Twelve percent of contigs with matches to the Heteroderidae and the Meloidogynidae had no homology to any C. elegans protein. Fifty-seven percent of the contigs did not match known sequences and some could be unique to P. thornei. These data provide substantial new information on the transcriptome of P. thornei, those genes common to migratory and sedentary endoparasitic nematodes, and provide additional understanding of genes required for different forms of parasitism. The data can also be used to identify potential genes to study host interactions and for crop protection. PMID- 22309970 TI - Impact of smoking on cognitive decline in early old age: the Whitehall II cohort study. AB - CONTEXT: Smoking is a possible risk factor for dementia, although its impact may have been underestimated in elderly populations because of the shorter life span of smokers. OBJECTIVE: To examine the association between smoking history and cognitive decline in the transition from midlife to old age. DESIGN: Cohort study. SETTING: The Whitehall II study. The first cognitive assessment was in 1997 to 1999, repeated over 2002 to 2004 and 2007 to 2009. PARTICIPANTS: Data are from 5099 men and 2137 women in the Whitehall II study, mean age 56 years (range, 44-69 years) at the first cognitive assessment. MAIN OUTCOME MEASURES: The cognitive test battery was composed of tests of memory, vocabulary, executive function (composed of 1 reasoning and 2 fluency tests), and a global cognitive score summarizing performance across all 5 tests. Smoking status was assessed over the entire study period. Linear mixed models were used to assess the association between smoking history and 10-year cognitive decline, expressed as z scores. RESULTS: In men, 10-year cognitive decline in all tests except vocabulary among never smokers ranged from a quarter to a third of the baseline standard deviation. Faster cognitive decline was observed among current smokers compared with never smokers in men (mean difference in 10-year decline in global cognition=-0.09 [95% CI, -0.15 to -0.03] and executive function=-0.11 [95% CI, 0.17 to -0.05]). Recent ex-smokers had greater decline in executive function ( 0.08 [95% CI, -0.14 to -0.02]), while the decline in long-term ex-smokers was similar to that among never smokers. In analyses that additionally took dropout and death into account, these differences were 1.2 to 1.5 times larger. In women, cognitive decline did not vary as a function of smoking status. CONCLUSIONS: Compared with never smokers, middle-aged male smokers experienced faster cognitive decline in global cognition and executive function. In ex-smokers with at least a 10-year cessation, there were no adverse effects on cognitive decline. PMID- 22309971 TI - Differences in the circuitry-based association of copy numbers and gene expression between the hippocampi of patients with schizophrenia and the hippocampi of patients with bipolar disorder. AB - CONTEXT: GAD67 regulation involves a network of genes implicated in schizophrenia and bipolar disorder. We have studied the copy number intensities of these genes in specific hippocampal subregions to clarify whether abnormalities of genomic integrity covary with gene expression in a circuitry-based manner. OBJECTIVE: To compare the copy number intensities of genes associated with GAD67 regulation in the stratum oriens of sectors CA3/2 and CA1 in patients with schizophrenia, patients with bipolar disorder, and healthy controls. DESIGN: Samples of sectors CA3/2 and CA1 were obtained from patients with schizophrenia, patients with bipolar disorder, and healthy controls. Genomic integrity was analyzed using microarrays, and the copy number intensities identified were correlated with the gene expression profile from a subset of these cases previously reported. SETTING: Harvard Brain Tissue Resource Center at McLean Hospital, Belmont, Massachusetts. PATIENTS: A total of 15 patients with schizophrenia, 15 patients with bipolar disorder, and 15 healthy controls. MAIN OUTCOME MEASURES: The copy number intensities for 28 target genes were individually examined using single nucleotide polymorphism microarrays and correlated with homologous messenger RNA (mRNA) fold changes. RESULTS: The copy number intensities examined using both microarrays and quantitative real-time polymerase chain reaction for the GAD67 gene were significantly decreased in sector CA3/2 of patients with schizophrenia and patients with bipolar disorder. Other genes associated with GAD67 regulation also showed changes in copy number intensities, and these changes were similar in magnitude and direction to those previously reported for mRNA fold changes in sector CA3/2 but not sector CA1. Moreover, the copy number intensities and mRNA fold changes were significantly correlated for both patients with schizophrenia (r=0.649; P=.0003) and patients with bipolar disorder (r=0.772; P=.0002) in sector CA3/2 but not in sector CA1. CONCLUSION: Insertions and deletions of genomic DNA in gamma-aminobutyric acid cells at a key locus of the hippocampal circuit are reflected in transcriptional changes in GAD67 regulation that are circuitry-based and diagnosis-specific. PMID- 22309972 TI - Influence of patient race and ethnicity on clinical assessment in patients with affective disorders. AB - CONTEXT: Rates of clinical diagnoses of schizophrenia in African American individuals appear to be elevated compared with other ethnic groups in the United States, contradicting population rates derived from epidemiologic surveys. OBJECTIVE: To determine whether African American individuals would continue to exhibit significantly higher rates of clinical diagnoses of schizophrenia, even after controlling for age, sex, income, site, and education, as well as the presence or absence of serious affective disorder, as determined by experts blinded to race and ethnicity. A secondary objective was to determine if a similar pattern occurred in Latino subjects. DESIGN: Ethnicity-blinded and unblinded diagnostic assessments were obtained in 241 African American individuals (mean [SD] age, 34.3 [8.1] years; 57% women), 220 non-Latino white individuals (mean [SD] age, 32.7 [8.5] years; 53% women), and 149 Latino individuals (mean [SD] age, 33.5 [8.0] years; 58% women) at 6 US sites. Logistic regression models were used to determine whether elevated rates of schizophrenia in African American individuals would persist after controlling for various confounding variables including blinded expert consensus diagnoses of serious affective illness. SETTINGS: Six academic medical centers across the United States. PARTICIPANTS: Six hundred ten psychiatric inpatients and outpatients. MAIN OUTCOME MEASURE: Relative odds of unblinded clinical diagnoses of schizophrenia in African American compared with white individuals. RESULTS: A significant ethnicity/race effect (chi(2)(2)=10.4, P=.01) was obtained when schizophrenia was narrowly defined, controlling for all other predictors. The odds ratio comparing African American with non-Latino white individuals was significant (odds ratio=2.7; 95% CI, 1.5-5.1). Similar differences between African American and white individuals occurred when schizophrenia was more broadly defined (odds ratio=2.5; 95% CI, 1.4-4.5). African American individuals did not differ significantly from white individuals in overall severity of manic and depressive symptoms but did evidence more severe psychosis. CONCLUSIONS: African American individuals exhibited significantly higher rates of clinical diagnoses of schizophrenia than non-Latino white subjects, even after controlling for covariates such as serious affective disorder. PMID- 22309973 TI - Suicidal thoughts and behavior with antidepressant treatment: reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine. AB - CONTEXT: The US Food and Drug Administration issued a black box warning for antidepressants and suicidal thoughts and behavior in children and young adults. OBJECTIVE: To determine the short-term safety of antidepressants by standard assessments of suicidal thoughts and behavior in youth, adult, and geriatric populations and the mediating effect of changes in depressive symptoms. DATA SOURCES: All intent-to-treat person-level longitudinal data of major depressive disorder from 12 adult, 4 geriatric, and 4 youth randomized controlled trials of fluoxetine hydrochloride and 21 adult trials of venlafaxine hydrochloride. STUDY SELECTION: All sponsor-conducted randomized controlled trials of fluoxetine and venlafaxine. DATA EXTRACTION: The suicide items from the Children's Depression Rating Scale-Revised and the Hamilton Depression Rating Scale as well as adverse event reports of suicide attempts and suicide during active treatment were analyzed in 9185 patients (fluoxetine: 2635 adults, 960 geriatric patients, 708 youths; venlafaxine: 2421 adults with immediate-release venlafaxine and 2461 adults with extended-release venlafaxine) for a total of 53 260 person-week observations. DATA SYNTHESIS: Suicidal thoughts and behavior decreased over time for adult and geriatric patients randomized to fluoxetine or venlafaxine compared with placebo, but no differences were found for youths. In adults, reduction in suicide ideation and attempts occurred through a reduction in depressive symptoms. In all age groups, severity of depression improved with medication and was significantly related to suicide ideation or behavior. CONCLUSIONS: Fluoxetine and venlafaxine decreased suicidal thoughts and behavior for adult and geriatric patients. This protective effect is mediated by decreases in depressive symptoms with treatment. For youths, no significant effects of treatment on suicidal thoughts and behavior were found, although depression responded to treatment. No evidence of increased suicide risk was observed in youths receiving active medication. To our knowledge, this is the first research synthesis of suicidal thoughts and behavior in depressed patients treated with antidepressants that examined the mediating role of depressive symptoms using complete longitudinal person-level data from a large set of published and unpublished studies. PMID- 22309974 TI - Enumerating metabolic pathways for the production of heterologous target chemicals in chassis organisms. AB - BACKGROUND: We consider the possibility of engineering metabolic pathways in a chassis organism in order to synthesize novel target compounds that are heterologous to the chassis. For this purpose, we model metabolic networks through hypergraphs where reactions are represented by hyperarcs. Each hyperarc represents an enzyme-catalyzed reaction that transforms set of substrates compounds into product compounds. We follow a retrosynthetic approach in order to search in the metabolic space (hypergraphs) for pathways (hyperpaths) linking the target compounds to a source set of compounds. RESULTS: To select the best pathways to engineer, we have developed an objective function that computes the cost of inserting a heterologous pathway in a given chassis organism. In order to find minimum-cost pathways, we propose in this paper two methods based on steady state analysis and network topology that are to the best of our knowledge, the first to enumerate all possible heterologous pathways linking a target compounds to a source set of compounds. In the context of metabolic engineering, the source set is composed of all naturally produced chassis compounds (endogenuous chassis metabolites) and the target set can be any compound of the chemical space. We also provide an algorithm for identifying precursors which can be supplied to the growth media in order to increase the number of ways to synthesize specific target compounds. CONCLUSIONS: We find the topological approach to be faster by several orders of magnitude than the steady state approach. Yet both methods are generally scalable in time with the number of pathways in the metabolic network. Therefore this work provides a powerful tool for pathway enumeration with direct application to biosynthetic pathway design. PMID- 22309975 TI - Fruit and vegetable intake is associated with frequency of breakfast, lunch and evening meal: cross-sectional study of 11-, 13-, and 15-year-olds. AB - BACKGROUND: Frequency of eating breakfast, lunch and evening meal as a determinant of fruit and vegetable intake among young people is little studied. We investigated whether irregular meal consumption was associated with fruit and vegetable intake among adolescents. We used separate analyses, and special emphasis was on the potentially modifying effect of sex and age. METHODS: Data were from the Danish contribution to the international collaborative Health Behavior in School-Aged Children Study (HBSC) in 2002. We used a questionnaire based, cross-sectional design to study schoolchildren aged 11, 13 and 15 years (n = 3913) selected from a random sample of schools in Denmark. Fruit intake and vegetable intake were measured by a food frequency questionnaire and analyses were conducted using multivariate logistic regression. RESULTS: Overall, statistically significant associations were found between irregular breakfast, lunch and evening meal consumption and low frequency of fruit intake and vegetable intake (breakfast: fruit OR = 1.42, vegetables OR = 1.48; lunch: fruit OR = 1.68, vegetables OR = 1.83; evening meal: vegetables OR = 1.70). No association was found for irregular evening meal consumption and low frequency of fruit intake. Analyses stratified by sex showed that the associations between irregular breakfast consumption and both fruit and vegetable intake remained statistically significant only among girls. When analyses were stratified by both sex and age, different patterns appeared. Overall, skipping meals seemed to be a less serious risk factor for low frequency of fruit and vegetable intake among younger participants compared with those who were older. This was especially evident for skipping breakfast. The same tendency was also seen for skipping lunch and evening meal, although the age pattern varied between boys and girls and between fruit and vegetable intake. CONCLUSION: Our results showed that irregular breakfast, lunch and evening meal consumption among adolescents was associated with a low frequency of fruit and vegetable intake and that sex and age may play a modifying role. The different associations observed in different age and sex groups indicate the importance of analysing fruit and vegetable intake and meal types separately. The results highlight the importance of promoting regular meal consumption when trying to increase the intake of fruit and vegetables among adolescents. PMID- 22309976 TI - Seasonal and biogeographical patterns of gastrointestinal parasites in large carnivores: wolves in a coastal archipelago. AB - Parasites are increasingly recognized for their profound influences on individual, population and ecosystem health. We provide the first report of gastrointestinal parasites in gray wolves from the central and north coasts of British Columbia, Canada. Across 60 000 km(2), wolf feces were collected from 34 packs in 2005-2008. At a smaller spatial scale (3300 km(2)), 8 packs were sampled in spring and autumn. Parasite eggs, larvae, and cysts were identified using standard flotation techniques and morphology. A subset of samples was analysed by PCR and sequencing to identify tapeworm eggs (n=9) and Giardia cysts (n=14). We detected >=14 parasite taxa in 1558 fecal samples. Sarcocystis sporocysts occurred most frequently in feces (43.7%), followed by taeniid eggs (23.9%), Diphyllobothrium eggs (9.1%), Giardia cysts (6.8%), Toxocara canis eggs (2.1%), and Cryptosporidium oocysts (1.7%). Other parasites occurred in <=1% of feces. Genetic analyses revealed Echinococcus canadensis strains G8 and G10, Taenia ovis krabbei, Diphyllobothrium nehonkaiense, and Giardia duodenalis assemblages A and B. Parasite prevalence differed between seasons and island/mainland sites. Patterns in parasite prevalence reflect seasonal and spatial resource use by wolves and wolf-salmon associations. These data provide a unique, extensive and solid baseline for monitoring parasite community structure in relation to environmental change. PMID- 22309977 TI - Catch-up growth in children after repair of Tetralogy of Fallot. AB - PURPOSE: To evaluate the growth of children after repair of Tetralogy of Fallot, as well as the influence of residual lesions and socio-economic status. METHODS: A total of 17 children, including 10 boys with a median age of 16 months at surgery, were enrolled in a retrospective cohort, in a tertiary care university hospital. Anthropometric (as z-scores), clinical, nutritional, and social data were collected. RESULTS: Weight-for-age and weight-for-height z-scores decreased pre-operatively and recovered post-operatively in almost all patients, most markedly weight for age. Weight-for-height z-scores improved, but were still lower than birth values in the long term. Long-term height-for-age z-scores were higher than those at birth, surgery, and 3 months post-operatively. Most patients showed catch-up growth for height for age (70%), weight for age (82%), and weight for height (70%). Post-operative residual lesions (76%) influenced weight-for-age z-scores. Despite the fact that most patients (70%) were from low-income families, energy intake was above the estimated requirement for age and gender in all but one patient. There was no influence of socio-economic status on pre- and post-operative growth. Bone age was delayed and long-term-predicted height was within mid-parental height limits in 16 children (93%). CONCLUSION: Children submitted to Tetralogy of Fallot repair had pre-operative acute growth restriction and showed post-operative catch-up growth for weight and height. Acute growth restriction could still be present in the long term. PMID- 22309978 TI - Comparing three screening tools for drug-induced parkinsonism in patients with advanced schizophrenia: a pilot study. AB - BACKGROUND: Drug-induced parkinsonism (DIP) is seen in one third of patients exposed to antipsychotic drugs and may lead to complications related to dysphagia and falls. Aside from skilled neurological examination, no tool has been validated to facilitate detection and follow-up. OBJECTIVE: In this pilot study, three validated screening instruments were tested in an age-biased cohort of schizophrenia patients, including four items of the Liverpool University Neuroleptic Side-Effects Rating Scale (LUNSERS) and two brief questionnaires designed for community survey of parkinsonism. METHOD: Fifty-six subjects living with chronic schizophrenia between 50 and 75 years of age underwent a motor evaluation along the original Unified Parkinson's Disease Rating Scale-section III and answered questions along the selected screening instruments, and results compared to those of 16 patients with Parkinson's disease (PD) and 15 neurologically unimpaired volunteers. Odds ratios, sensitivity, specificity, and their 95% confidence intervals, were calculated. RESULTS: All three screening instruments correctly identified the PD state and distinguished PD from healthy participants. Eighteen (32%) schizophrenic patients displayed objective motor signs of parkinsonism. A single item of the LUNSERS (shakiness) significantly distinguished DIP from DIP-free patients, with a sensitivity of 61.1% and a specificity of 83.3%. The positive predictive value was 63.5% and the negative predictive value was 81.9%. The two other screening methods showed insufficient predictive value. CONCLUSION: Apart from a single query on shakiness, none of the tools examined were adequate to screen for DIP in patients treated for schizophrenia. A different instrument is necessary to monitor this important adverse effect in schizophrenia. PMID- 22309979 TI - Noladin ether, a putative endocannabinoid, enhances motivation to eat after acute systemic administration in rats. AB - BACKGROUND AND PURPOSE Endocannabinoid systems are strongly implicated in the physiological control of appetite and eating behaviour, with cannabinoid CB(1) receptor agonists and antagonists, respectively, increasing or decreasing food intake. This study examined the acute actions of the putative endocannabinoid noladin ether on food intake and eating motivation, assessing how it affects the amount of work expended by animals to obtain food. EXPERIMENTAL APPROACH Non deprived male rats were injected systemically with noladin ether to assess its acute effects on ad libitum feeding of a standard laboratory diet. Additionally, the effects of noladin on lever pressing for palatable food were determined using a progressive ratio (PR) operant paradigm. KEY RESULTS Noladin dose dependently increased 2 h food intake, with a significant effect over 1 h after a dose of 0.5 mg.kg(-1). In the PR test, this hyperphagic dose of noladin ether promoted sustained high rates of responding and significantly increased the total number of lever presses and break-point. These latter effects were prevented by pretreatment with 1.0 mg.kg(-1) of the selective CB(1) antagonist surinabant (SR147778), that alone had no effect on responding. CONCLUSIONS AND IMPLICATIONS This is the first report of hyperphagia induced by acute noladin administration, and the first description of behavioural actions in rats. Consistent with prevailing notions about the role of endocannabinoids in appetite, a hyperphagic dose of noladin markedly increased efforts expended by animals to obtain food. Thus, noladin exerts a specific action on eating motivation; possibly promoting eating by increasing the incentive value of food. PMID- 22309980 TI - Chrysin abrogates cisplatin-induced oxidative stress, p53 expression, goblet cell disintegration and apoptotic responses in the jejunum of Wistar rats. AB - Cisplatin (cis-diamminedichloroplatinum (II) (CDDP)) is a commonly used chemotherapeutic drug for the treatment of numerous forms of cancer, but it has pronounced adverse effects, namely nephrotoxicity, ototoxicity, neurotoxicity, hepatotoxicity, diarrhoea and nausea. CDDP-induced emesis and diarrhoea are also marked toxicities that may be due to intestinal injury. Chrysin (5,7 dihydroxyflavone), a natural flavone commonly found in many plants, possesses multiple biological activities, such as antioxidant and anti-inflammatory properties. In the present study, we investigated the protective effect of chrysin against CDDP-induced jejunal toxicity. The plausible mechanism of CDDP induced jejunal toxicity includes oxidative stress, p53 and apoptosis via up regulating the expression of caspase-6 and -3. Chrysin was administered to Wistar rats orally in maize oil. A single intraperitoneal injection of CDDP was given and the animals were killed after 24 h of CDDP injection. Chrysin ameliorated CDDP-induced lipid peroxidation, increase in xanthine oxidase activity, glutathione depletion, decrease in antioxidant (catalase, glutathione reductase, glutathione peroxidase and glucose-6-phosphate dehydrogenase) and phase-II detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities. Chrysin attenuated CDDP-induced goblet cell disintegration, enhanced expression of p53 and apoptotic tissue damage. Histological findings further substantiated the protective effects of chrysin against CDDP-induced damage in the jejunum. The results of the present study demonstrate that oxidative stress and apoptosis are closely associated with CDDP-induced toxicity and chrysin shows the protective efficacy against CDDP-induced jejunum toxicity possibly via attenuating the oxidative stress and apoptotic tissue damage. PMID- 22309981 TI - The biomechanics of locomotor compensation after peripheral nerve lesion in the rat. AB - Functional recovery in animal models of nervous system disorders commonly involves behavioural compensation, in which animals alter the use of their limbs after injury, making it difficult to distinguish 'true' recovery from substitution of novel movements. The purpose of this study is to investigate how abnormal movements are produced by using biomechanical assessment of limb joint motion, an approach commonly used to diagnose human pathological gait. Rats were trained to cross a runway whilst kinetic (ground reaction forces) and kinematic (limb segment positions) data were synchronously recorded. Inverse dynamic analysis was used to calculate limb joint moments, or torques, and joint mechanical power throughout the stride for major joints of the forelimbs and hindlimbs, both before and after denervation of a major ankle extensor muscle. Before surgery, rats moved with joint moment and power profiles comparable to other quadrupeds, with differences attributable to species variation in limb posture. After surgery, rats trotted asymmetrically, with a near plantigrade stance of the left hindlimb. Surprisingly, ankle joint moments and power were largely preserved, with dramatic reductions in range of motion and joint moments at the proximal joints of the affected limb. Stiffening of the proximal limb compensated for increased compliance at the ankle but decreased the total mechanical work done by the injured limb. In turn, more work was done by the opposite, i.e. uninjured, hindlimb. This is the first study to quantify the biomechanical adjustments made within and between limbs in laboratory rodents after nervous system injury. PMID- 22309982 TI - D1 and D2 dopamine receptor antagonists decrease behavioral bout duration, without altering the bout's repeated behavioral components, in a naturalistic model of repetitive and compulsive behavior. AB - Nest building behavior in the pregnant female rabbit (Oryctolagus cuniculus) is a model for compulsive behavior in Obsessive Compulsive Disorder (OCD). This behavior comprises a cycle of repeated, stereotyped components (collecting straw, entering nest box and depositing the straw there, returning to collect more straw), which itself is repeated 80+ times in a single bout that lasts approximately 50min. The bout, in turn, is repeated if necessary, according to the rabbit's perception of whether or not the nest is finished. We administered SCH23390 (5-100MUg/kg; D1/D5 antagonist) or raclopride (0.05-1.0mg/kg; D2/D3 antagonist), subcutaneously to day 28 pregnant female rabbits, 30 or 60min before placing straw inside their home cage. At doses that minimally affected ambulatory behavior in open field (5-12.5MUg/kg SCH23390, 0.5-1.0mg/kg raclopride), both antagonists dramatically reduced bout duration while not significantly affecting the initiation of straw carrying behavior, the sequential performance of the individual cycle components, maximum cycle frequency, or the total number of bouts performed. These results point to an important role for dopamine neurotransmission for the prolonged expression of a normal, repetitive and compulsive-like behavior. Moreover, the finding that dopamine receptor antagonists decrease the time spent engaged in repetitive behavior (without significantly altering the form of the repetitive behavior itself) suggests a possible explanation for why neuroleptics can be clinically effective for treating OCD. PMID- 22309983 TI - Amitriptyline attenuates astrocyte activation and morphine tolerance in rats: role of the PSD-95/NR1/nNOS/PKCgamma signaling pathway. AB - The tricyclic antidepressant amitriptyline binds with high affinity to N-methyl-d aspartate receptors (NMDARs) and inhibits NMDAR-mediated events. Activation of the postsynaptic density protein-95 (PSD-95)/NMDAR-mediated downstream signaling cascade, including neuronal nitric oxide synthase (nNOS) and protein kinase gamma (PKCgamma), has been shown to be involved in morphine tolerance. The present study examined the potential effect of amitriptyline on chronic morphine infusion induced spinal PSD-95/NMDAR/nNOS/PKCgamma signaling in morphine tolerance. Male Wistar rats were implanted with an intrathecal catheter and received an intrathecal infusion of saline or amitriptyline (15 MUg/h), morphine+saline (tolerance induction, 15 MUg/h), or morphine+amitriptyline for 5 days. Co administration of amitriptyline with morphine not only preserved the antinociceptive effect of morphine, but also attenuated astrocyte activation in the rat spinal cord dorsal horn. On day 5 after drug infusion, increased expression and phosphorylation of spinal membrane NMDAR NR1 subunit and expression of PSD-95 were observed following chronic morphine infusion and these effects were attenuated by amitriptyline co-infusion. Upregulation of NMDAR induced intracellular nNOS expression was also inhibited by amitriptyline co infusion in chronic morphine-infused rats. Furthermore, amitriptyline co-infusion significantly inhibited morphine-induced PKCgamma expression in both the cytosol and membrane of spinal neurons. These findings suggest that the attenuation of morphine tolerance caused by amitriptyline is due to downregulation of NMDAR NR1 subunit expression in the synaptosomal membrane accompanied by decreased expression of the scaffolding protein PSD-95. The effects of amitriptyline in attenuating astrocyte activation and reversing tolerance to morphine may be due, at least in part, to inhibition of the PSD-95/NMDAR NR1/nNOS/PKCgamma signaling cascade. PMID- 22309984 TI - The organization and anatomy of narrative comprehension and expression in Lewy body spectrum disorders. AB - OBJECTIVE: Patients with Lewy body spectrum disorders (LBSD) such as Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies exhibit deficits in both narrative comprehension and narrative expression. The present research examines the hypothesis that these impairments are due to a material neutral deficit in organizational executive resources rather than to impairments of language per se. We predicted that comprehension and expression of narrative would be similarly affected and that deficits in both expression and comprehension of narrative would be related to the same anatomic distribution of prefrontal disease. METHOD: We examined 29 LBSD patients and 26 healthy seniors on their comprehension and expression of narrative discourse. For comprehension, we measured accuracy and latency in judging events with high and low associativity from familiar scripts such as "going fishing." The expression task involved maintaining the connectedness of events while narrating a story from a wordless picture book. RESULTS: LBSD patients were impaired on measures of narrative organization during both comprehension and expression relative to healthy seniors. Measures of organization during narrative expression and comprehension were significantly correlated with each other. These measures both correlated with executive measures but not with neuropsychological measures of lexical semantics or grammar. Voxel-based morphometry revealed overlapping regressions relating frontal atrophy to narrative comprehension, narrative expression, and measures of executive control. CONCLUSIONS: Difficulty with narrative discourse in LBSD stems in part from a deficit of organization common to comprehension and expression. This deficit is related to prefrontal cortical atrophy in LBSD. PMID- 22309985 TI - State of art in porphyrin Langmuir-Blodgett films as chemical sensors. AB - Porphyrins are tetrapyrrolic macrocycles with a fascinating and multifarious variegation of properties of essential significance in up-to-date and leading technologies. From a different point of view, the Langmuir-Blodgett technique allows the immobilisation of films with an accurate regulation of molecular organisation and thickness. As a logical upshot, this manuscript concerns a substantial object of consideration in contemporary research, the utilisation of Langmuir-Blodgett multilayers of porphyrins in sensing elements for the detection of analytes in different matrices. Investigations on the morphological, optical, structural and surface characteristics of these films are remarkably related to the significant properties of sensors with the ultimate goal of rationalising the innermost intercourses between the sensing behaviour and the peculiarities and molecular organisation brought about by the deposition method. The integration of the typical electrical and optical characteristics of porphyrins with the potentialities of the Langmuir-Blodgett multilayer has originated not only encouraging projects but has afforded also certainties on the accomplishment of operative chemical sensors. PMID- 22309986 TI - A new flow-cytometry-based opsonophagocytosis assay for the rapid measurement of functional antibody levels against Group B Streptococcus. AB - Opsonophagocytosis is the primary mechanism for the clearance of Group B Streptococcus (GBS) by the host, and levels of opsonic antibodies may correlate with protection in preclinical models. A killing-based opsonophagocytosis assay (OPA), can be used to determine the functional activity of vaccine-induced GBS specific antibodies. The assay, which measures the number of bacterial colonies surviving phagocytic killing in the presence of specific antibodies and complement, is rather expensive, time-consuming and poorly standardized. Here we describe a rapid, sensitive and reproducible fluorescent OPA assay (fOPA) based on flow cytometry analysis (FACS), which allows internalized bacteria to be distinguished from those associated to the plasma membrane of phagocytic cells. Fixed GBS were labeled with pHrodoTM, a fluorescent dye which dramatically increases the emitted fluorescence at the acidic conditions present in the phagocytic endosomal compartment. Labeled bacteria were incubated with HL-60 cells differentiated to phagocytes, antibodies and complement, and then analyzed by FACS. A further improvement to our method, allowing to reduce assay variability, consisted on a step of selection of effector cells among the HL-60 population. Analysis of sera from mice immunized with different GBS vaccines revealed comparable sensitivity and specificity with the traditional killing OPA assay (kOPA), and a good correlation between the fluorescent signal of bacteria internalized by HL-60 phagocytes and killing. Remarkably, the pHrodo-based approach reduced the variability observed with other fOPA assays. The obtained data indicate the proposed fOPA as a reliable and useful tool for functional antibody assessment. PMID- 22309987 TI - Comparative study on metal homeostasis and detoxification in two Antarctic teleosts. AB - The main characteristic of Antarctic seawater is its low constant temperature and its high concentration of O(2), which can increase the formation rate of reactive oxygen species (ROS), together with a natural occurrence of elevated cadmium and copper levels. In the present paper, we studied the presence of cadmium, copper and zinc, metallothioneins (MTs) and glutathione (GSH), and antioxidant enzyme activities in the Antarctic teleosts Trematomus bernacchii and Trematomus newnesi, in order to determine the influence of the peculiar physico-chemical features of the Antarctic marine environment on these physiological defence systems in two species of teleosts. In both of them, cadmium and copper accumulation occurs mostly in the liver. T. bernacchii accumulates zinc mostly in the hepatic tissue, whereas T. newnesi does not show a preferential accumulation site. In addition to the intra-specific analysis, we decided to compare the two species of the Trematomus genus in order to verify if the different feeding habits and motility of these fish affects metal accumulation. Our results show that the liver of T. bernacchii accumulates cadmium and zinc at a higher extent with respect to T. newnesi. Glutathione (GSH) and metallothioneins (MTs) are present in great quantity in the liver of both species. Moreover liver is the tissue which generally showed the highest antioxidant enzyme levels. The results provide further insights in the physiological mechanisms evolved by animals living in this extreme environment. PMID- 22309988 TI - Drotrecogin alfa (activated)...a sad final fizzle to a roller-coaster party. AB - Following the failure of PROWESS-SHOCK to demonstrate efficacy, Eli Lilly and Company withdrew drotrecogin alfa (activated) from the worldwide market. Drotrecogin was initially approved after the original trial, PROWESS, was stopped early for overwhelming efficacy. These events prompt consideration of both the initial approval decision and the later decision to withdraw. It is regrettable that the initial decision was made largely on a single trial that was stopped early. However, the decision to approve was within the bounds of normal regulatory practice and was made by many approval bodies around the world. Furthermore, the overall withdrawal rate of approved drugs remains very low. The decision to withdraw was a voluntary decision by Eli Lilly and Company and likely reflected key business considerations. Drotrecogin does have important biologic effects, and it is probable that we do not know how best to select patients who would benefit. Overall, there may still be a small advantage to drotrecogin alfa, even used non-selectively, but the costs of determining such an effect with adequate certainty are likely prohibitive, and the point is now moot. In the future, we should consider ways to make clinical trials easier and quicker so that more information can be available in a timely manner when considering regulatory approval. At the same time, more sophisticated selection of patients seems key if we are to most wisely test agents designed to manipulate the septic host response. PMID- 22309989 TI - An ecological perspective on medication adherence. AB - Adherence to a prescribed medication regimen is influenced not only by characteristics of the individual patient, but also by factors within the patient's environment, or so-called system level factors. Until now, however, health care system factors have received relatively little attention in explaining medication nonadherence. Ecological models might serve as a framework to help explain the influence of health care system factors on patient behavior (e.g., adherence). In an ecological model, different levels of factors influence patients' behavior, i.e. factors at the patient-level, micro- (provider and social support), meso- (health care organization), and macro (health policy) levels. In order to understand medication adherence and implement interventions to improve medication adherence, factors at these different levels should be taking into consideration. This paper describes an ecological model compromised of the most important factors at the patient-, micro-, meso- and macro-levels. PMID- 22309990 TI - Providing diabetes self-management support in rural primary care clinics with nurse partners. AB - This study examined the roles and effectiveness of nurse partner-provided diabetes self-management (DSM) support in five rural primary care clinics. There were two to nine providers and one nurse partner in each clinic; nurses were licensed practical nurses (LPNs) in all but one clinic. Interviews with providers and observations of patient interactions assessed nurse roles, clinic processes, and communication patterns. Using immersion-crystallization methods, three major themes explained nurse partner role variation: "gatekeeper" role of providers, compression of time and space within clinic work flow, and nurses' educational background and experience. While nurses' education and experience were important, clinics where providers facilitated nurse participation in DSM support through focused communication and commitment of time and space most effectively integrated DSM support into their practice. Some quantitative measures improved; notably glycated hemoglobin level and patients' frequency of blood glucose measurement. Study findings provide guidance on using nurses in primary care clinics to provide DSM. PMID- 22309991 TI - A critical review of a spirituality intervention. AB - Although there is a growing interest in the topic of spirituality, there are few reports of spiritual interventions and limited empirical data to support their effectiveness. As health care practices become increasingly evidence based, the reliance on empirical data is critical. This article describes the spiritual intervention developed by the author and documents the testing of its effectiveness with clinical and nonclinical populations. The findings from a series of studies have been mixed. Preliminary studies reported that the intervention positively influenced patients' outcomes, including overall quality of life and reduced selected stress responses. Significant positive trends were found that supported the potential effectiveness of the intervention for a variety of populations and clinical settings. However, subsequent testing in clinical trials indicated limited effect of the intervention although there were several noteworthy findings. The author discusses the implications of these findings for future investigations. PMID- 22309992 TI - Hemoglobin Q-Iran detected in family members from Northern Iran: a case report. AB - INTRODUCTION: Hemoglobin Q-Iran (alpha75Asp->His) is an important member of the hemoglobin Q family, molecularly characterized by the replacement of aspartic acid by histidine. The first report of hemoglobin Q-Iran and the nomenclature of this hemoglobinopathy dates back to 1970. Iran is known as a country with a high prevalence of alpha- and beta-thalassemia and different types of hemoglobinopathy. Many of these variants are yet to be identified as the practice of molecular laboratory techniques is limited in this part of the world. Applying such molecular methods, we report the first hemoglobin Q-Iran cases in Northern Iran. CASE PRESENTATION: An unusual band was detected in an isoelectric focusing test and cellulose acetate electrophoresis of a sample from a 22-year-old Iranian man from Mazandaran Province. Capillary zone electrophoresis analysis identified this band as hemoglobin Q. A similar band was also detected in his mother's electrophoresis (38 years, Iranian ethnicity). The cases underwent molecular investigation and the presence of a hemoglobin Q-Iran mutation was confirmed by the amplification refractory mutation system polymerase chain reaction method. Direct conventional sequencing revealed a single guanine to cytosine missense mutation (c.226G > C; GAC >CAC) at codon 75 in the alpha-globin gene in both cases. CONCLUSION: The wide spectrum and high frequency of nondeletional alpha globin mutations in Mazandaran Province is remarkable and seem to differ considerably from what has been found in Mediterranean populations. This short communication reports the first cases of patients with hemoglobin Q found in that region. PMID- 22309993 TI - Theoretical simulation of Kelvin probe force microscopy for Si surfaces by taking account of chemical forces. AB - A new method of theoretical simulation for Kelvin probe force microscopy (KPFM) imaging on semiconductor or metal samples is proposed. The method is based on a partitioned real space (PR) density functional based tight binding (DFTB) calculation of the electronic states to determine the multi-pole electro-static force, which is augmented with the chemical force obtained by a perturbation treatment of the orbital hybridization. With the PR-DFTB method, the change of the total energy is calculated together with the induced charge distribution in the tip and the sample by their approach under an applied bias voltage, and the KPFM images, namely the patterns of local contact potential difference (LCPD) distribution, are obtained with the minimum condition of the interaction force. However, since the interaction force is due to electro-static multi-poles, the spatial resolution of the KPFM images obtained by PR-DFTB is limited to the nano scale range and an atom-scale resolution cannot be attained. By introducing an additional chemical force, i.e., the force due to the orbital hybridization, we succeeded in reproducing atom-scale resolution of KPFM images. Case studies are performed for clean and impurity embedded Si surfaces with Si tip models. PMID- 22309994 TI - Validation of a single-platform, volumetric, flow cytometry for CD4 T cell count monitoring in therapeutic mobile unit. AB - BACKGROUND: A mobile health unit may be useful to follow up adult and pediatric patients on antiretroviral treatment and living in remote areas devoid of laboratory facilities. The study evaluated the use of the simplified, robust, single-plateform, volumetric, pan-leucogating Auto40 flow cytometer (Apogee Flow Systems Ltd, Hemel Hempstead, UK) for CD4 T cell numeration in a mobile unit, compared against a reference flow cytometry method. METHODS: The therapeutic mobile unit of the Laboratoire National de Sante Hygiene Mobile, Yaounde, Cameroon, was equipped with the Auto40. A FACSCalibur flow cytometer (Becton Dickinson Immuno-cytometry System, San Jose, CA, USA) was used as reference method. EDTA-blood samples from volunteers were first subjected to CD4 T cell count in the mobile unit, and an aliquot was sent within 4 hours to Centre International de Reference Chantal Biya, Yaounde, for FACSCalibur assay. RESULTS: Two HIV screening campaigns with the mobile unit were organised in December 2009 and January 2010. The campaign in the suburb of Yaounde which was 20 km from the reference laboratory included 188 volunteers comprising 93 children less than 5 years old. The campaign in Ambang Bikok (53 km far from Yaounde) included 69 adult volunteers. In Yaounde suburb, mean +/- standard deviation (SD) CD4 T cell count was 996 +/- 874 cells/MUl by Auto40, and 989 +/- 883 cells/MUl by FACSCalibur; in Ambang Bikok, mean +/- SD CD4 T cell count was 1041 +/- 317 cells/MUl by Auto40, and 1032 +/- 294 cells/MUl by FACSCalibur. Results by Auto40 and FACSCalibur were highly correlated in Yaounde (r(2) = 0.982) as in Ambang Bikok (r(2) = 0.921). Bland-Altman analysis showed a close agreement between Auto40 and FACSCalibur results expressed in absolute count as in percentage in Yaounde and Ambang Bikok. When pooling the 257 CD4 T cell count measurements, the Auto40 yielded a mean difference of +7.6 CD4 T cells/MUl higher than by reference flow cytometry; and the sensitivity and specificity of Auto40 in enumerating absolute CD4 T cell counts of less than 200 cells/MUl were 87% and 99%, respectively, and in enumerating absolute CD4 T cell counts of less than 350 cells/MUl were 87% and 98%, respectively. The intrarun and interun precisions of the Auto40 assay assessed in the mobile unit were 5.5% and 7.9%, respectively. CONCLUSIONS: The Auto40 flow cytometer installed in a therapeutic mobile unit and operated far from its reference laboratory gave a perfect correlation with the reference method, and could be useful in carrying out immunological monitoring of HIV-infected patients living in areas without access to laboratory facilities. PMID- 22309995 TI - Atypical left ventricular outflow tract aneurysm diagnosed by three-dimensional echocardiography. PMID- 22309996 TI - Genetic differences among Vietnamese Haplorchis taichui populations using the COI genetic marker. AB - Adults of the fish-borne intestinal trematode species Haplorchis taichui were collected from humans in three provinces of Vietnam: Ha Giang, Thanh Hoa and Quang Tri. Genetic analysis revealed three groups of the parasite from clustering dendrograms, correlating with the localities in which they were collected. Measurements of evolutionary divergence over sequence pairs were greater between the different populations than within them, which indicated that the three populations were genetically different. The significance (Fst= 0.73; P value < 0.05) of the genetic variation of the three studied populations implied that genetic separation of the populations had already occurred, which may have been caused by a low gene flow among the different H. taichui populations. Factors contributing to the low gene flow may include isolation resulting from the intermediate-host fish rarely being sold outside of the rural commune where they are raised and the enclosed aquacultural areas themselves. PMID- 22309997 TI - Blood feeding in juvenile Paragnathia formica (Isopoda: Gnathiidae): biochemical characterization of trypsin inhibitors, detection of anticoagulants, and molecular identification of fish hosts. AB - The 3 post-marsupial juvenile stages of the gnathiid isopod, Paragnathia formica, are haematophagous ectoparasites of fishes that may, in heavy infestations, cause host mortality. Protein digestion in fed stage 3 juveniles is accomplished by cysteine proteinases, but what bioactive compounds attenuate host haemostatic, inflammatory and immunological responses during feeding is unknown. Trypsin inhibitory activity and anticoagulant activity were detected in crude extracts of unfed P. formica stage 1 juveniles; fractionation of stage 1 crude extracts by ion exchange chromatography resulted in 3 preparations each displaying these bioactivities. Further characterization revealed anti-thrombin activity in 2 of these preparations, whilst the third displayed the strongest anticoagulant activity that targeted a factor of the intrinsic coagulation pathway. Three trypsin inhibitors (18 kDa, 21 kDa, and 22 kDa) were also detected using reverse zymography. In parallel, homogenates of fed stage 2 and 3 juveniles were used to identify their fish hosts by amplifying the 16S mitochondrial rDNA and 18S genomic rDNA vertebrate gene regions. Blood from at least 4 fish families had been ingested by separate individuals during feeding. This study demonstrates that trypsin inhibitors and anticoagulants are present in P. formica juveniles which could suppress host haemostatic, inflammatory and immunological responses during feeding, and that juveniles are not host specific. PMID- 22309998 TI - Prognostic significance of angiogenesis in relation to Ki-67, p-53, p-27, and bcl 2 expression in embryonal tumors. AB - AIM: We investigated the angiogenesis and density of newly formed blood vessels in embryonal tumors in relation to Ki-67, bcl-2, p-53 and p-27 expression. METHODS: Forty-five children with embryonal tumors were enrolled in the study. Forty patients had a medulloblastoma (MB) and 5 patients had atypical teratoid/rhabdoid tumor (AT/RT). RESULTS: In MB, the 5-year PFS and OS was 62.5 and 70%, respectively. Patients with Ki-67 index >50%, bcl-2 index >30% and higher density of new vessels were associated with worse survival. In the multivariate analysis, Ki-67 index was identified as a factor with independent prognostic power. In AT/RTs, high density of new vessels (>25 HRF) was observed in 3 patients and Ki-67 index over 25% was found in 4 patients. CONCLUSION: Increased Ki-67, bcl-2 and density of new vessels are of prognostic value for the disease outcome in MB. PMID- 22309999 TI - Role of BI-1 (TEGT)-mediated ERK1/2 activation in mitochondria-mediated apoptosis and splenomegaly in BI-1 transgenic mice. AB - Bax Inhibitor-1 (BI-1) is an evolutionally conserved apoptotic suppressor and belongs to the BI-1 family of proteins, which contain BI-1-like transmembrane domains. As their cellular functions and regulatory mechanisms remain incompletely understood, we compared their anti-apoptotic properties. Forced expression of BI-1 resulted in the most effective suppression of stress-induced apoptosis, compared with other family members, together with significant extracellular signal-regulated kinase (ERK)1/2 activation. BI-1-mediated ERK1/2 activation led to the suppression of mitochondria-mediated reactive oxygen species (ROS) production. Involvement of the ERK signaling pathway in BI-1 induced anti-apoptotic effects was confirmed by knockdown studies with ERK- or BI 1-specific siRNA. Moreover, we produced transgenic (TG) mice overexpressing BI-1, and the relationship between ERK1/2 activation and the suppression of ROS production or apoptosis was confirmed in mouse embryonic fibroblast (MEF) cells derived from these mice. Interestingly, we found that BI-1 TG mice showed splenomegaly and abnormal megakaryopoiesis. Taken together, our results suggest that BI-1-induced ERK1/2 activation plays an important role in the modulation of intracellular ROS generation and apoptotic cell death and may also affect autoimmune response. PMID- 22310000 TI - Regulation of leptin expression by 17beta-estradiol in human placental cells involves membrane associated estrogen receptor alpha. AB - The placenta produces a wide number of molecules that play essential roles in the establishment and maintenance of pregnancy. In this context, leptin has emerged as an important player in reproduction. The synthesis of leptin in normal trophoblastic cells is regulated by different endogenous biochemical agents, but the regulation of placental leptin expression is still poorly understood. We have previously reported that 17beta-estradiol (E(2)) up-regulates placental leptin expression. To improve the understanding of estrogen receptor mechanisms in regulating leptin gene expression, in the current study we examined the effect of membrane-constrained E(2) conjugate, E-BSA, on leptin expression in human placental cells. We have found that leptin expression was induced by E-BSA both in BeWo cells and human placental explants, suggesting that E(2) also exerts its effects through membrane receptors. Moreover E-BSA rapidly activated different MAPKs and AKT pathways, and these pathways were involved in E(2) induced placental leptin expression. On the other hand we demonstrated the presence of ERalpha associated to the plasma membrane of BeWo cells. We showed that E(2) genomic and nongenomic actions could be mediated by ERalpha. Supporting this idea, the downregulation of ERalpha level through a specific siRNA, decreased E BSA effects on leptin expression. Taken together, these results provide new evidence of the mechanisms whereby E(2) regulates leptin expression in placenta and support the importance of leptin in placental physiology. PMID- 22310001 TI - [Venous thrombosis prophylaxis in hospitalized patients still infrequently used]. PMID- 22310002 TI - [Can we afford the best for all patients?]. PMID- 22310003 TI - [Combined ventilation/perfusion SPECT/CT is best for diagnosing pulmonary embolism]. AB - The diagnosis of pulmonary embolism (PE) is usually established by a combination of clinical assessment, D-dimer test and imaging with either lung scintigraphy or pulmonary multidetector computed tomography angiography (CTA). Which of the two methods to use in PE diagnostic has not been determined and very limited data comparing these modalities are available. With the use of hybrid scanners, ventilation/perfusion-single-photon-emission-tomography (V/Q-SPECT) in combination with low-dose CT without contrast enhancement is feasible and should probably be considered first-line imaging in diagnosing PE. PMID- 22310004 TI - [Culture and biology in psychopharmacological treatment of ethnic minorities]. AB - The success of psychopharmacological treatment is conditional on biological as well as cultural factors. Significant biological factors in this context are the decomposition of psychotropic drugs and the relevant receptors. Comparable cultural factors are: understanding the disease and conceptions of the best treatment that affects adherence and the expectations of the effect of the treatment. This status describes our current knowledge in these areas and suggests a practical application of this in clinical work. PMID- 22310005 TI - [Treatment of peritonsillar abscess]. AB - Peritonsillar abscess (PTA) is associated with high morbidity and can cause serious and life-threatening complications. In Denmark, the most commonly isolated bacteria are Fusobacterium necrophorum and Streptococcus pyogenes gr. A. The incidence of PTA in Denmark is 41/100,000/year, the highest incidence ever reported for PTA. There is no definite consensus on the treatment. We recommend most patients treated with puncture and antibiotics as outpatients, and if necessary acute tonsillectomy instead of interval tonsillectomy. Steroids may be of value. PMID- 22310006 TI - [Modafinil in the treatment of depression]. AB - A systematic review of the literature on modafinil as adjunctive treatment to antidepressants in patients with major depression and residual symptoms of fatigue and drowsiness is presented. Several open-labelled studies have shown good results on treatment with modafinil. However, only a few randomised controlled clinical trials exist. These have methodological weaknesses and their results are contradictory. If modafinil is used in highly selected patients with severe fatigue its potential interactions with antidepressants must be borne in mind. Furthermore, discontinuation of the drug should be tried after a couple of months, as one study suggests that the effect wears off. In addition, the drug is rather expensive. PMID- 22310007 TI - [Pancreatic panniculitis is necrosis of adipocytes in the subcutis followed by intense pain]. AB - We report an unusual history of pain in a young patient in the intensive care unit. A 33 year-old alcoholic male with acute pancreatitis had generalized intense pain and developed erythema on the lower truncus and the lower extremities. Treatment with different antibiotics, antihistamines and topical potent steroid cream were all ineffective. A biopsy showed necrotic adipocytes characteristic for pancreatic panniculitis. We suggest that pancreatic panniculitis should be considered in patients with erythema, pain and known pancreatic disease. PMID- 22310008 TI - [Severe laryngomalacia in children can be treated with laser assisted surgery]. AB - Laryngomalacia is the most common cause for congenital stridor. The stridor is caused by collapse of supraglottic structures during inspiration. Two severe cases treated with laser-assisted supraglottoplasty are presented. Our cases as well as the literature describe good effect of the treatment with only few complications. However since laryngomalacia usually it is a benign condition, which in most cases resolves spontaneously within the first two years of the patients life, this treatment should only be used in severe cases, where the alternative treatment would be tracheotomia. PMID- 22310009 TI - [Atypical cause of scapular winging due to exostosis of the scapula]. AB - The most common cause of winging of the scapula is paralysis of the anterior serratus muscle, predominantly because of damage to the long thoracicus nerve. We present a case with a 12 year-old boy, who experienced increasing winging of the scapula over the latest four years. He suffered from minor pain especially when exercising sports. The condition was caused by an osteochondroma on the ventral side of the scapula. We discuss the different causes of winging of the scapula. PMID- 22310010 TI - Common liability to drug addictions: theory, research, practice. PMID- 22310011 TI - Ecdysone signaling in adult Drosophila melanogaster. AB - The steroid hormone 20-hydroxyecdysone and its EcR/USP receptor are vital during arthropod development for coordinating molting and metamorphosis. Traditionally, little attention has been given to potential post-developmental functions for this hormone signaling system. However, recent studies in Drosophila melanogaster indicate that the hormone and receptor are present and active in adults and that mutations decreasing hormone or receptor levels affect diverse processes such as reproduction, behavior, stress resistance, and lifespan. We review the current state of knowledge regarding adult hormone production and titers and discuss receptor expression and activity in order to identify potential mechanisms which explain the observed mutant phenotypes. Finally, we describe future research directions focused on identifying isoform-specific functions of EcR, distinguishing effects from EcR/USP gene activation and repression, and determining how ecdysone signaling impacts different tissue types. PMID- 22310012 TI - Effects of temperature on development, survival and reproduction of insects: experimental design, data analysis and modeling. AB - The developmental response of insects to temperature is important in understanding the ecology of insect life histories. Temperature-dependent phenology models permit examination of the impacts of temperature on the geographical distributions, population dynamics and management of insects. The measurement of insect developmental, survival and reproductive responses to temperature poses practical challenges because of their modality, variability among individuals and high mortality near the lower and upper threshold temperatures. We address this challenge with an integrated approach to the design of experiments and analysis of data based on maximum likelihood. This approach expands, simplifies and unifies the analysis of laboratory data parameterizing the thermal responses of insects in particular and poikilotherms in general. This approach allows the use of censored observations (records of surviving individuals that have not completed development after a certain time) and accommodates observations from temperature transfer treatments in which individuals pass only a portion of their development at an extreme (near threshold) temperature and are then placed in optimal conditions to complete their development with a higher rate of survival. Results obtained from this approach are directly applicable to individual-based modeling of insect development, survival and reproduction with respect to temperature. This approach makes possible the development of process-based phenology models that are based on optimal use of available information, and will aid in the development of powerful tools for analyzing eruptive insect population behavior and response to changing climatic conditions. PMID- 22310013 TI - Impact of vena cava filters on in-hospital case fatality rate from pulmonary embolism. AB - BACKGROUND: The effects of vena cava filters on case fatality rate are not clear, although they are used increasingly in patients with pulmonary embolism. The purpose of this investigation is to determine categories of patients with pulmonary embolism in whom vena cava filters reduce in-hospital case fatality rate. METHODS: In-hospital all-cause case fatality rate according to the use of vena cava filters was determined in patients with pulmonary embolism discharged from short-stay hospitals throughout the United States using data from the Nationwide Inpatient Sample. RESULTS: In-hospital case fatality rate was marginally lower in stable patients who received a vena cava filter: 21,420 of 297,700 (7.2%) versus 135,240 of 1,712,800 (7.9%) (P<.0001). Filters did not improve in-hospital case fatality rate if deep venous thrombosis was diagnosed in stable patients. A few stable patients (1.4%) received thrombolytic therapy. Such patients who received a vena cava filter had a lower case fatality rate than those who did not: 550 of 8550 (6.4%) versus 2950 of 19,050 (15%) (P<.0001). Unstable patients who received thrombolytic therapy had a lower in-hospital case fatality rate with vena cava filters than those who did not: 505 of 6630 (7.6%) versus 2600 of 14,760 (18%) (P<.0001). Unstable patients who did not receive thrombolytic therapy also had a lower in-hospital case fatality rate with a vena cava filter: 4260 of 12,850 (33%) versus 19,560 of 38,000 (51%) (P<.0001). CONCLUSION: At present, it seems prudent to consider a vena cava filter in patients with pulmonary embolism who are receiving thrombolytic therapy and in unstable patients who may not be candidates for thrombolytic therapy. Future prospective study is warranted to better define in which patients a filter is appropriate. PMID- 22310014 TI - Revitalizing the history and clinical examination. PMID- 22310015 TI - Disentangling disability in the fear avoidance model: more than pain interference alone. PMID- 22310016 TI - Overexpression of calreticulin in malignant and benign breast tumors: relationship with humoral immunity. AB - OBJECTIVE: Calreticulin is a multicompartmental protein which regulates many important cellular responses. The aim of this study was to elucidate whether the intensity and location of calreticulin overexpression in tumor cells are related to the elevated humoral immunity to calreticulin in patients with benign or malignant breast disease. METHODS: This study involved 27 patients with benign and 58 patients with malignant breast tumors before surgical resection and 38 healthy volunteers. Cytoplasmatic or membranous calreticulin overexpression in malignant or benign cells in paraffin-embedded tissues was determined using immunohistochemistry. Levels of the serum anti-calreticulin autoantibodies were detected by ELISA. RESULTS: Statistically significant differences between serum levels of IgA of anti-calreticulin antibodies in controls and patients with breast tumors, and between controls and patients with nonmalignant breast diseases were found, but no statistically significant differences were found between levels of serum IgG anti-calreticulin antibodies. Humoral immunity to calreticulin developed against cytoplasmatic and co-localized membranous calreticulin was not correlated to the intensity of its overexpression and was present even in the absence of its membranous localization. CONCLUSIONS: The degree of calreticulin overexpression in lobular breast carcinoma is lower than in ductal breast carcinoma. Elevated concentrations of anti-calreticulin IgA antibodies were present more frequently in patients with metastasis in locoregional lymph nodes in comparison to anti-calreticulin IgG antibodies. PMID- 22310017 TI - gamma-Spectroscopy measurement of natural radioactivity and assessment of radiation hazard indices in soil samples from oil fields environment of Delta State, Nigeria. AB - The analysis of naturally occurring radionuclides ((226)Ra, (232)Th and (40)K) has been carried out in soil samples collected from oil and gas field environment of Delta state, using gamma spectroscopy operated on a Canberra vertical high purity 2"*2" NaI(TI) detector. The activity concentration of the samples ranges from 19.2 +/- 5.6Bqkg(-1) to 94.2 +/- 7.7Bqkg(-1) with mean value of 41.0 +/- 5.0Bqkg(-1) for (226)Ra, 17.1 +/- 3.0Bqkg(-1) to 47.5 +/- 5.3Bqkg(-1) with mean value of 29.7 +/- 4Bqkg(-1) for (232)Th and 107.0 +/- 10.2Bqkg(-1) to 712.4 +/- 38.9Bqkg(-1) with a mean value of 412.5 +/- 20.0Bqkg(-1) for (40)K. These values obtained are well within the world range and values reported elsewhere in other countries, but are little above some countries reported average values and some part of Nigeria. The study also examined some radiation hazard indices, the mean values obtained are, 98.5 +/- 12.3Bq.kg(-1), 0.8Bqkg(-1), 54.6etaGyh(-1), 0.07MUSvy(-1), 0.3 and 0.4 for Radium equivalent activity (Ra(eq)), Representative level index (Igamma), Absorbed Dose rates (D), Annual Effective Dose Rates (E(ff) Dose), External Hazard Index (H(ex)) and Internal Hazard Index (H(in)) respectively. These calculated hazard indices to estimate the potential radiological health risk in soil and the dose rate associated with it are well below their permissible limit. The soil and sediments from the study area provide no excessive exposures for inhabitants and can be use as construction materials without posing any immediate radiological threat to the public. However, oil workers in the fields and host communities are cautioned against excess exposure to avoid future accumulative dose of these radiations from sludge and sediment of this area. PMID- 22310018 TI - Metabolite profiling reveals clear metabolic changes during somatic embryo development of Norway spruce (Picea abies). AB - Progress on industrial-scale propagation of conifers by somatic embryogenesis has been hampered by the differences in developmental capabilities between cell lines, which are limiting the capture of genetic gains from breeding programs. In this study, we investigated the metabolic events occurring during somatic embryo development in Norway spruce to establish a better understanding of the fundamental metabolic events required for somatic embryo development. Three embryogenic cell lines of Norway spruce (Picea abies (L.) Karst) with different developmental capabilities were studied during somatic embryo development from proliferation of proembryogenic masses to mature somatic embryos. The three different cell lines displayed normal, aberrant and blocked somatic embryo development. Metabolite profiles from four development stages in each of the cell lines were obtained using combined gas chromatography-mass spectrometry. Multivariate discriminant analyses of the metabolic data revealed significant metabolites (P <= 0.05) for each development stage and transition. The results suggest that endogenous auxin and sugar signaling affects initial stages of somatic embryo development. Furthermore, the results highlight the importance of a timed stress response and the presence of stimulatory metabolites during late stages of embryo development. PMID- 22310019 TI - Reversal of atomic contrast in scanning probe microscopy on (111) metal surfaces. AB - We study the origin of atomic contrast on Cu(111) and Pt(111) surfaces probed by a non-contact atomic force microscope and scanning tunnelling microscope. First principles simulations of the interaction between the atoms of the scanning tip and those of the probed surface show a dependence of the resulting contrast on the tip-sample distance and reveal a close relation between contrast changes and relaxation of atomic positions in both the tip and the sample. Contrast reversion around the distance where the short-range attractive atomic force reaches its maximum is predicted for both types of microscopies. We also demonstrate a relation between the maximal attractive force in a F-z atomic force spectroscopy and the chemical identity of the apex atom on the imaging tip. PMID- 22310020 TI - [Diagnosis of hypochromic microcytic anemia in children]. AB - Iron deficiency is the most frequent cause of hypochromic microcytic anemia in children, but other causes, some of them requiring specific management, may be involved. Checking the iron-status is absolutely mandatory. When iron-status parameters are low, inadequate intake, malabsorption, blood loss, and abnormal iron utilization must be tested. In absence of iron deficiency, alpha- and beta globin and heme biosynthetic gene status must be checked. Assessing the iron stock level is difficult, because there is an overlap between the values observed in iron-replete and iron-deprived patients, so that at least 2 iron-status parameters must be below normal for diagnosing iron deficiency. Furthermore, inflammation may also mimic some characteristics of iron deficiency. Diagnosing iron deficiency leads to prescribing iron supplementation with follow-up at the end and 3 months after cessation of treatment. When iron stores are not replete at the end of treatment, compliance and dosage must be reevaluated and occult bleeding sought. The latter is also required when the iron store decreases 3 months after cessation of iron replacement. PMID- 22310021 TI - Pharmacology update: tapentadol for neuropathic pain. AB - Neuropathic pain in a common problem encountered in palliative care. When neuropathic pain is diagnosed, appropriate treatment is important in limiting the severe psychosocial impairment that can ensue with undertreated pain. Proper evaluation of the patient to clarify the type of pain experienced is the first step to determine appropriate management. Tapentadol is an oral mu-opioid receptor agonist and a noradrenaline reuptake inhibitor developed by Ortho-McNeil Janssen Pharmaceuticals and approved by the Food and Drug Administration in November 2008 for the treatment of moderate-to-severe acute pain in adult patients and for chronic pain in August 2011 in an extended release form. Tapentadol has been studied for use in nociceptive pain but few studies have yet been done to assess its efficacy in the treatment of neuropathic pain. PMID- 22310022 TI - Negotiating the boundary between paid and unpaid hospice workers: a qualitative study of how hospice volunteers understand their work. AB - OBJECTIVE: To explore the nurse-volunteer relationship in a day hospice. METHOD: Underpinned by an interpretive approach, face-to-face semistructured interviews were conducted with 12 day hospice volunteers. FINDINGS: The nature and dynamics of the relationship between nursing staff and volunteers within the day hospice were characterized by increasing formality and changes in the division of labor, which challenged smooth working relationships. CONCLUSIONS: Volunteers see their role as becoming increasingly formalized partly as a response to increasing administrative demands on hospice nurses. The willingness of volunteers to take on new roles is variable. For volunteers to feel secure and valued and working relationships to remain strong, the process of how boundaries between paid and unpaid workers are negotiated needs to be transparent. PMID- 22310023 TI - Revision and validation of a medication assessment tool for chronic cancer pain management. AB - The medication assessment tool for cancer pain management (MAT-CP) measures the quality of medication use in relation to guidelines. The original MAT-CP was reviewed, modified and tested at a comprehensive cancer center in Jordan. The tool comprised 30 criteria covering six different aspects of pain management. Seventy patients were included, males 41 (59%), females 29 (41%), mean age 49 (range, 20-79) years. The overall level of adherence to guidelines was 78% with good inter-rater reliability (kappa= 0.899). The tool's implementation showed opportunities for improvement in pain management at our institution. The MAT-CP was revised and validated for the first time outside Europe. This tool can be routinely used to assess and compare the quality of pain management in different institutions. PMID- 22310024 TI - Qualitative pain classification in hospice and pain therapy unit. AB - In this study, we investigated patient's meaning attribution to pain in hospice and pain therapy unit, using a qualitative approach: narrative-based medicine. The data presented here were related to patients (n = 17) hospitalized in Rimini Hospice (Italy). These data were compared to those of patients (n = 21) with noncancer pain (control sample). The interviews were then analyzed according to the technique of thematic narrative analysis. The results of our research identified a differential process in pain processing in relationship to the meaning that the patient attributed to pain. The thematic analysis of the interviews allowed the inductive construction of a specific network of pain dimensions, which were summarized in "the pain chronogram." PMID- 22310025 TI - Integrative palliative care, advance directives, and hospital outcomes of critically ill older adults. AB - OBJECTIVE: To examine the associations between palliative care types and hospital outcomes for patients who have or do not have advance directives. METHOD: Using administrative claims and clinical data for critically ill older adults (n = 1291), multivariable regressions examined the associations between palliative care types and hospital outcomes by advance directive status. RESULTS: Integrative palliative care was associated with lower hospital costs, lower adjusted probability of in-hospital deaths, and higher adjusted probability of hospice discharges. There was no difference in hospital outcomes by palliative care types in those with advance directives. CONCLUSION: Significantly lower hospital costs and in-hospital deaths with higher hospice discharges were observed in integrative palliative care compared to consultative palliative care, but these findings were diminished with the presence of advance directives. PMID- 22310027 TI - A comparison of the FMRFamide-like peptide proteolytic activities of preparations from two plant-parasitic nematodes (Heterodera glycines and Meloidogyne incognita): possible targets for novel control. AB - Proteolytic activities in extracts from the plant-parasitic nematodes Heterodera glycines and Meloidogyne incognita were examined for their abilities to digest three FRET-modified peptide substrates representing members of the large FMRFamide-like peptide (FLP) family in nematodes. Included were sequences distributed across all nematode species (KSAYMRFa and KHEYLRFa) and a sequence confined to a narrow range of plant-parasitic nematodes (KHEFVRFa). Species variations were observed among substrate affinities, reaction rates and effect of protease inhibitors. K m values for KHEYLRFa (1.48 +/- 0.34 MUm) and KSAYMRFa (2.13 +/- 0.24 MUm) in H. glycines were each lower (P< 0.05) than those for the same substrates in M. incognita (5.26 +/- 1.30 MUm and 3.90 +/- 0.61 MUm, respectively). The K m of KHEFVRFa was lower (P< 0.05) in M. incognita (5.83 +/- 0.36 MUm) than in H. glycines (11.01 +/- 1.26 MUm). Reaction rates (V max/min/MUg) for KHEYLRFa were the same for both species, but KSAYMRFa and KHEFVRFa digestion rates were each nearly twofold higher (P< 0.05) in M. incognita than in H. glycines. Digestion of KSAYMRFa was strongly inhibited in both species by 4-(2-aminoethyl)-benzenesulfonyl-fluoride-HCl (AEBSF) and EDTA, but M. incognita was more sensitive (P< 0.05) to inhibition. AEBSF and EDTA (both at 1 mm) inhibited M. incognita activity 62.3% and 36.6% more, respectively, than H. glycines activity. Serine protease inhibition differed significantly (P< 0.05) between the two species. Maximum inhibition of M. incognita (76%) occurred at 1.85 mm AEBSF while maximum inhibition of H. glycines was 40% at 1.19 mm AEBSF. PMID- 22310028 TI - Rare occurrence of PALB2 mutations in ovarian cancer patients from the Volga-Ural region. PMID- 22310029 TI - Cross-sectional area of the posterior extensor muscles of the cervical spine in whiplash injury patients versus healthy volunteers--10 year follow-up MR study. AB - INTRODUCTION: Long-term follow-up studies focusing on the posterior extensor muscles in patients suffering from whiplash injury are scarce. The purpose of this study was to elucidate the changes in the posterior extensor muscles 10 years after whiplash injury. METHODS: Twenty-three patients who had suffered from whiplash injury in 1994-1996 and had undergone MRI using a 1.5-T superconductive imager participated in this follow-up study (13 males, 10 females, mean age 51.8 years, mean follow-up 11.5 years). In addition, 60 healthy volunteers who had undergone MRI in the same period were included as controls (36 males, 24 females, mean age 47.8 years, mean follow-up 11.1 years). All participants underwent follow-up MRI. The cross-sectional areas of the deep posterior muscles (CSA) including the multifidus, semispinalis cervicis, semispinalis capitis, and splenius capitis were digitally measured at C3-4, C4-5, and C5-6 using NIH image. The long-term changes in the CSA were compared between the two groups. In addition, correlations between the CSA and cervical spine-related symptoms were evaluated. RESULTS: The mean total CSA per patient (the sum of the area from C3-4 to C5-6) was 4811.6+/-878.4 mm(2) in the whiplash patients and 4494.9+/-1032.7 mm(2) in the controls at the initial investigation (p=0.20), and 5173.4+/-946.1 mm(2) and 4713.0+/-1065.3 mm(2) at the follow-up (p=0.07). The mean change in CSA over time was 361.8+/-804.9 mm(2) in the whiplash patients and 218.1+/-520.7 mm(2) in the controls (p=0.34). Ten whiplash patients (43.5%) had neck pain and 11 (47.8%) had shoulder stiffness. However, there was no difference in the change in CSA over time between the symptomatic and asymptomatic patients. CONCLUSIONS: There was no significant difference in the change in CSA between whiplash patients and healthy volunteers after a 10-year follow-up period. In both groups, the cross-sectional area slightly increased at follow-up. In addition, there was no association between the change in CSA and clinical symptoms such as neck and shoulder pain. These results suggest that whiplash injury is not associated with symptomatic atrophy of the posterior cervical muscles over the long term. PMID- 22310030 TI - Development of RNA aptamers for detection of Salmonella Enteritidis. AB - We developed and evaluated RNA aptamers to analyze their potential for use in detecting Salmonella Enteritidis. The selected aptamer was observed to specifically bind to Salmonella Enteritidis without any cross-reactivity to other Salmonella serovars. Thus, this study suggests that aptamers specific to Salmonella Enteritidis have a high potential for use in presumptive presumptive screening methods or alternative serotyping methods. PMID- 22310031 TI - A fluorometric method for evaluation of pharmacological activity against intracellular Leishmania amastigotes. AB - In this work a simple and novel method to evaluate the efficacy of compounds on intracellular Leishmania amastigotes by using a fluorometric assay has been developed. The new method is sensitive, easy to perform and scalable for high throughput and therefore it could be validated for screening of new anti leishmanial agents. PMID- 22310032 TI - Plasma beta-amyloid peptides levels: a pilot study in bipolar depressed patients. AB - BACKGROUND: Patients with mood disorders present a great risk for dementia and generally for cognitive decline. Low levels of beta-amyloid peptide 1-42 (Abeta42) and high Abeta40/Abeta42 ratio have been associated with this risk and have been reported also in geriatric patients suffering from depression. The aim of the present study was to compare the plasma levels of Abeta40 and Abeta42 in patients with bipolar depression and healthy subjects, and to correlate them with the characteristics of clinical course. METHODS: Levels of Abeta40 and Abeta42 were measured by using specific ELISA kits in 16 patients with bipolar depression and in 16 control subjects with a negative history for somatic, psychiatric, neurological and substance abuse disorders. RESULTS: Patients presented significantly lower plasma Abeta42 levels and higher Abeta40/Abeta42 ratio, as compared with control subjects. Moreover, a significant negative correlation was found between Abeta42 plasma levels and the duration of the illness, while a positive correlation was detected between the Abeta40/Abeta42 ratio and the number of affective episodes. LIMITATIONS: The major limitations of the study are the small sample size, the scanty characterization of the illness episodes and the fact that all the patients were under psychopharmacological treatment. CONCLUSION: Although further research is necessary to establish firm conclusions, the present data would suggest that changes in plasma levels of different Abeta peptides might represent a useful tool to identify the risk for cognitive decline in bipolar patients. PMID- 22310033 TI - Which symptoms are indicative of DSMIV depression in cancer settings? An analysis of the diagnostic significance of somatic and non-somatic symptoms. AB - BACKGROUND: There have been few studies that have attempted to examine the phenomenology of comorbid depression, in particular the diagnostic value of individual somatic and non-somatic symptoms when attempting to diagnose depression following cancer. METHODS: We approached 279 patients up to three times within 9 months of first presentation with a diagnosis of cancer, and collected data following a total of 558 contacts. 176 contacts (31%) were in a palliative stage. Symptoms were elicited by self-report PHQ9 and HADS-D scales. The prevalence of major depression was 12.7% but 29.6% had major or minor depression (any depressive disorder) according to modified DSMIV criteria. RESULTS: All symptoms of depression were significant more common in depressed versus non-depressed cancer patients regardless of stage. Against broadly defined any depressive disorder (ADD) the most accurate diagnostic symptoms were all somatic (namely trouble falling or staying asleep or sleeping too much; feeling tired or having little energy; poor appetite or overeating; trouble concentrating on things such as reading). Indeed the optimal symptom insomnia had good case finding properties and screening properties used alone. A two step combination of three questions give a sensitivity of 100% and specificity of 91.6% against ADD. Against major depressive disorder (MDD) both somatic and non-somatic symptoms were valuable (including but not limited to the PHQ2 stem questions). Only low energy was poorly discriminating which may suggest that the standard ICD10 criteria may not be optimal. When considering depression as defined by the HADS-D (>= 11), then the three most influential symptoms were psychological closely followed by somatic symptoms. When looking for MDD and HADS-D depression, no single symptom was a good proxy for depression highlighting a possible shortcoming if clinicians attempt to rely on one single question. In a subset of palliative patients feeling bad about yourself and moving or speaking slowly were less influential and outperformed by poor appetite/overeating and feeling tired or having little energy. CONCLUSION: This research suggests that most somatic symptoms remain influential when diagnosing depression in the context of cancer and hence should not be omitted indiscriminately, even in palliative stages. The optimal symptoms for diagnosing depression will depend on whether a narrow concept of depression or a broad concept of depression is considered clinically important. PMID- 22310034 TI - Are early-onset cannabis smokers at an increased risk of depression spells? AB - BACKGROUND: A recent research focus is a set of hypothesized adult-onset mental health disturbances possibly due to early-onset cannabis use (EOCU, onset <18 years). We seek to estimate the suspected EOCU-associated excess odds of experiencing an incident depression spell during adulthood, with comparisons to never cannabis smokers and those with delayed cannabis onset (i.e., not starting to smoke cannabis until adulthood). METHODS: The National Surveys on Drug Use and Health (NSDUH) assess non-institutionalized community-dwelling residents of the United States after probability sampling each year. In aggregate, the NSDUH analytical sample included 173,775 adult participants from survey years 2005-2009 (74-76% of designated respondents). Standardized computer-assisted interviews collected information on background determinants, age of first cannabis use, and depression spell onset. Logistic regression was used to estimate EOCU-depression spell associations in the form of odds ratios, with statistical adjustment for sex, age, race/ethnicity, years of cannabis involvement, tobacco cigarette onset, and alcohol onset. RESULTS: About 1 in 10 experienced a depression spell during adulthood, and both early-onset and adult-onset cannabis smokers had a modest excess odds of a depression spell compared to never cannabis smokers, even with covariate adjustment (OR=1.7 and 1.8, respectively; both p<0.001). Estimates for early- and adult-onset cannabis smokers did not statistically differ from one another. LIMITATIONS: Shared diathesis that might influence both EOCU and adult onset depression spell is controlled no more than partially, as will be true until essentially all known early-life shared vulnerabilities are illuminated. CONCLUSION: Cannabis smoking initiated at any age signals a modest increased risk of a spell of depression in adulthood, even when adjusted for suspected confounding variables studied here. Delaying cannabis onset until adulthood does not appear to diminish the cannabis-associated risk. PMID- 22310035 TI - Pre-adult onset and patterns of suicidality in patients with a history of recurrent depression. AB - BACKGROUND: This report assesses the association between age of onset of major depression and later suicidality in a sample of 276 recurrently depressed patients recruited for the Oxford/Bangor Staying Well after Depression (SWAD) Trial, and interviewed when in remission. METHODS: The study enrolled adult patients with a history of at least three episodes of non-psychotic major depressive disorder from primary care and psychiatric care practices and through community advertisements. At study entry, all participants estimated the age of their first onset of a major depressive episode and completed both self-report and interview-based assessments of past and current suicidal ideation and behavior. Participants were divided into pre-adult and adult onset groups using a cut-off age of 18. RESULTS: Forty-eight percent of the sample reported a pre adult age of onset. Pre-adult age of onset was significantly associated with suicidality, both from self-report and from interviewer assessment even when adjusting for differences in age, gender, employment status, length of the disorder and early adversity. LIMITATIONS: Relevant variables were all assessed through retrospective reports. CONCLUSIONS: Pre-adult age of onset is closely associated with risk for and severity of later suicidality, replicating, in a sample of patients assessed when in remission, findings from studies that assessed patients when currently depressed. The association of pre-adult age of onset with suicidality is not due to differences in sociodemographic variables, length of the disorder and early adversity. PMID- 22310036 TI - The role of executive function in posttraumatic stress disorder: a systematic review. AB - BACKGROUND: Although posttraumatic stress disorder (PTSD) has been associated with disturbances in verbal memory, studies examining executive functioning in PTSD show mixed results. METHODS: A systematic review and meta-analysis were performed to compare executive functioning in patients with current PTSD and controls without any psychiatric disorder. Standard mean differences (SMD) in executive functioning scores were calculated using random-effects models. Covariates were added to examine whether differences exist between subgroups. RESULTS: Across 18 studies, 1080 subjects were included. In comparison with 431 exposed controls and 227 healthy controls, 422 people with PTSD showed significantly impaired executive functioning. Subgroup analyses revealed more pronounced differences between PTSD patients and exposed controls than healthy controls. Male gender, higher age, war trauma, and higher severity of co-morbid depressive symptoms were related to poorer executive functioning in PTSD patients compared to exposed controls. LIMITATIONS: Due to insufficient data and heterogeneity, not all subgroup differences or characteristics could be taken into account. CONCLUSIONS: Overall, PTSD patients were found to show impaired executive functioning. Future research should further elucidate the subgroup effects and focus on clinical implications with regard to daily functioning and treatment outcome. PMID- 22310037 TI - A prospective study of relationships between propositions about risk and driver speeding. AB - Risk propositions are specific and modifiable hypotheses that people hold about the outcomes of risk-taking behavior. According to fuzzy trace theory (FTT), risk propositions arise from the subjective and idiosyncratic interpretations that people make about the meaning of risk information, and form the primary basis of decision-making. A community sample of 255 drivers was interviewed at baseline (T1), 6 weeks after baseline (T2) and 14 weeks after baseline (T3). We tested whether propositions about speeding-related risk at time 1 (T1) would predict speeding at time 3 (T3), controlling perceptions of speeding-related danger and other speeding-related variables (the perceived possibility of being caught and the enjoyment and excitement to be gained from speeding) measured at time 2 (T2). We also tested whether relationships between T1 propositions and T3 speeding would be mediated by T2 perceptions of danger. T1 propositions predicted T3 speeding independently of the control variables, and we also found evidence consistent with mediation by T2 danger. In line with FTT, risk propositions were not scaleable as a single dimension, but generally predicted speeding as independent entities. Taken together these findings support the view that drivers perceive speeding risk as a series of potentially modifiable propositions which may have item-specific influences on speeding behavior. PMID- 22310038 TI - Physician input and licensing of at-risk drivers: a review of all-inclusive medical evaluation forms in the US and Canada. AB - This article details a systematic review of medical evaluation forms in support of licensing decisions for medically at-risk drivers. Comparisons were made between all-inclusive forms utilized by 52 State and Provincial Departments of Motor Vehicles (DMVs) in the US and Canada. Comparisons focused on length, format, content, instructional quality, medical coverage, ease of use, and other qualitative characteristics. Median page length was 2 (range 1-10), and mean word count was 1083 (494-3884). Common response options included open-ended (98%), forced choice (87%), and check box (81%). While the majority of forms (77%) required driver consent, only 24% requested information from the driver. Less than half (46%) included text on confidentiality protection. While all forms requested general medical information, just over half included specific sections for vision (54%) and cognitive/neurological conditions (56%). Most forms (81%) required that a judgment be made concerning driver safety, and half prompted for possible license restrictions. Criterion-based quality ratings were assigned on a five-point Likert scale by group consensus. One third of forms were rated as marginal or poor in comprehensiveness and utility, and just two garnered an excellent overall rating. Findings are discussed relative to current research on driver fitness and elements of a proposed model form. Best practice recommendations include a page length limitation, emphasis on in-person evaluation (i.e., as opposed to a records-only review), prompts to collect crash and other driving history information, clear instructions and stepwise format, content prompts across relevant medical categories, documentation of functional status and impairment levels, options for driving with restrictions in lieu of de licensing, and emphasis on relative (vs. absolute) clinical judgments of overall driver safety. PMID- 22310039 TI - Injury tolerance of tibia for the car-pedestrian impact. AB - Lower limbs are normally the first contacted body region during car-pedestrian accidents, and easily suffer serious injuries. The previous tibia bending tolerances for pedestrian safety were mainly developed from three-point bending tests on tibia mid-shaft. The tibia tolerances of other locations are still not investigated enough. In addition, tibia loading condition under the car pedestrian impact should be explored to compare with the three-point bending. This work aims to investigate the injury tolerance of tibia fracture with combined experimental data and numerical simulation. Eleven new reported quasi static bending tests of tibia mid-shaft, and additional eleven dynamic mid-shaft bending test results in the previous literature were used to define injury risk functions. Furthermore, to investigate the influence of tibia locations on bending tolerance, finite element simulations with lower limb model were implemented according to three-point bending and pedestrian impact conditions. The regressive curve of tibia bending tolerance was obtained from the simulations on the different impact locations, and indicated that tibia fracture tolerance could vary largely due to the impact locations for the car-pedestrian crash. PMID- 22310040 TI - Novel application of red-light runner proneness theory within traffic microsimulation to an actual signal junction. AB - Building on previous research a conceptual framework, based on potential conflicts analysis, has provided a quantitative evaluation of 'proneness' to red light running behaviour at urban signalised intersections of different geometric, flow and driver characteristics. The results provided evidence that commonly used violation rates could cause inappropriate evaluation of the extent of the red light running phenomenon. Initially, an in-depth investigation of the functional form of the mathematical relationship between the potential and actual red-light runners was carried out. The application of the conceptual framework was tested on a signalised intersection in order to quantify the proneness to red-light running. For the particular junction studied proneness for daytime was found to be 0.17 north and 0.16 south for opposing main road approaches and 0.42 east and 0.59 west for the secondary approaches. Further investigations were carried out using a traffic microsimulation model, to explore those geometric features and traffic volumes (arrival patterns at the stop-line) that significantly affect red light running. In this way the prediction capability of the proposed potential conflict model was improved. A degree of consistency in the measured and simulated red-light running was observed and the conceptual framework was tested through a sensitivity analysis applied to different stop-line positions and traffic volume variations. The microsimulation, although at its early stages of development, has shown promise in its ability to model unintentional red light running behaviour and following further work through application to other junctions, potentially provides a tool for evaluation of alternative junction designs on proneness. In brief, this paper proposes and applies a novel approach to model red-light running using a microsimulation and demonstrates consistency with the observed and theoretical results. PMID- 22310041 TI - Incidence trends of traumatic spinal cord injury and traumatic brain injury in Spain, 2000-2009. AB - AIMS: The aim of the present study was to estimate the incidence of hospital discharges for traumatic spinal cord injury (TSCI) and traumatic brain injury (TBI) in Spain by injury circumstances (traffic crashes and others), injury severity, gender and age group and to describe its trends over the period 2000 2009. METHODS: It is a study of trends that includes hospital discharges with a primary diagnosis of TSCI or TBI. Crude and age-standardised rates were calculated per million inhabitants. Changes in rates between 2000 and 2009 were assessed through calculation of the relative risk adjusted for age, using Poisson regression. RESULTS: Between 2000 and 2009 in Spain, 10,274 patients were admitted for traumatic TSCI, and 206,503 for TBI. The annual incidence rate for TSCI was 23.5 per million, that for TBI was 472.6 per million. The overall incidence rate for TSCI fell significantly between 2000 and 2009 by 24.2% (traffic-related 40.9%, other 12.9%), as did that for TBI (23.8% overall, 60.2% traffic-related, with no change for other circumstances). Among people aged 65 years and over, no change was observed for TSCI, incidence of TBI fell significantly when due to traffic crashes, but there was a dramatic increase of 87% in men and 89.3% in women when due to other circumstances. CONCLUSIONS: Over the last decade the incidence of these types of injury has fallen significantly when the injury resulted from traffic crashes, and to a lesser extent when from other circumstances. However TBI incidence among people aged 65 and over injured in non-traffic-related circumstances has risen dramatically. PMID- 22310042 TI - Development and evaluation of an intervention to reduce rip current related beach drowning. AB - The objective of this research was to evaluate a campaign to improve beachgoer recognition of calm-looking rip currents, known to contribute to surf drowning. Posters, postcards, and brochures conveying the message "Don't get sucked in by the rip" were distributed in an intervention area. Beachgoers were interviewed in this and a similar control area one year before and immediately after the intervention (respective response rates: 69.9% and 82.3%), Consenting respondents were sent follow-up questionnaires after approximately 6 months and 55% responded. In the intervention area, 28.8% of post-intervention, and 57.2% of follow-up respondents, had seen our campaign. At post-intervention, intervention respondents demonstrated improvement (relative to baseline) in intentions to swim away from a calm-looking rip, ability and confidence in identifying a rip, intention never to swim at unpatrolled beaches, and responses to being caught in a rip, compared to the control respondents. Similar improvements were observed post-intervention for respondents in the intervention area who had seen our campaign (relative to those who had not), and at 6 month follow-up for intervention respondents (relative to control respondents). The relatively brief print-based campaign was effective in warning beachgoers about calm-looking rips. PMID- 22310043 TI - Beware of the dog? An observational study of dog-related musculoskeletal injury in the UK. AB - Although owning a dog confers numerous health benefits, dogs can cause falls resulting in musculoskeletal injury and fractures. We conducted a prospective observational study over a two-month period to investigate the incidence and epidemiology of dog-related musculoskeletal injury. All patients attending the Emergency Department, trauma ward or fracture clinic were asked whether their injury was caused by a dog. Thirty-seven patients were identified. There were 26 fractures, 10 soft-tissue injuries and one head injury. Seventeen patients were admitted to the hospital and sixteen cases required an operation. Older people were statistically more likely to sustain a fracture (p=0.0003) or require hospital admission (p=0.02). Mechanisms of injury are discussed and can be classified into direct or indirectly caused by the dog. The most common injury mechanism was being pulled over by a dog on a lead. Injury avoidance strategies are discussed. We conclude that dogs are a potential hazard, particularly to the elderly and the morbidity associated with these injuries may offset the health benefits conferred by dog ownership. PMID- 22310044 TI - Nickel binding and [NiFe]-hydrogenase maturation by the metallochaperone SlyD with a single metal-binding site in Escherichia coli. AB - SlyD (sensitive to lysis D) is a nickel metallochaperone involved in the maturation of [NiFe]-hydrogenases in Escherichia coli (E. coli) and specifically contributes to the nickel delivery step during enzyme biosynthesis. This protein contains a C-terminal metal-binding domain that is rich in potential metal binding residues that enable SlyD to bind multiple nickel ions with high affinity. The SlyD homolog from Thermus thermophilus does not contain the extended cysteine- and histidine-rich C-terminal tail of the E. coli protein, yet it binds a single Ni(II) ion tightly. To investigate whether a single metal binding motif can functionally replace the full-length domain, we generated a truncation of E. coli SlyD, SlyD155. Ni(II) binding to SlyD155 was investigated by using isothermal titration calorimetry, NMR and electrospray ionization mass spectrometry measurements. This in vitro characterization revealed that SlyD155 contains a single metal-binding motif with high affinity for nickel. Structural characterization by X-ray absorption spectroscopy and NMR indicated that nickel was coordinated in an octahedral geometry with at least two histidines as ligands. Heterodimerization between SlyD and another hydrogenase accessory protein, HypB, is essential for optimal hydrogenase maturation and was confirmed for SlyD155 via cross-linking experiments and NMR titrations, as were conserved chaperone and peptidyl-prolyl isomerase activities. Although these properties of SlyD are preserved in the truncated version, it does not modulate nickel binding to HypB in vitro or contribute to the maturation of [NiFe]-hydrogenases in vivo, unlike the full-length protein. This study highlights the importance of the unusual metal-binding domain of E. coli SlyD in hydrogenase biogenesis. PMID- 22310045 TI - Phagemid vectors for phage display: properties, characteristics and construction. AB - Phagemids are filamentous-phage-derived vectors containing the replication origin of a plasmid. Phagemids usually encode no or only one kind of coat proteins. Other structural and functional proteins necessary to accomplish the life cycle of phagemid are provided by the helper phage. In addition, other elements such as molecular tags and selective markers are introduced into the phagemids to facilitate the subsequent operations, such as gene manipulation and protein purification. This review summarizes the elements of the phagemids and their corresponding functions. Finally, the possible trends and future direction to improve the characteristics of the phagemids are highlighted. PMID- 22310046 TI - Crystal structure of Pseudomonas aeruginosa Tsi2 reveals a stably folded superhelical antitoxin. AB - In the competition for niches in natural resources, Pseudomonas aeruginosa utilizes the type VI secretion system to inject the toxic protein effector Tse2 into bacteria on cell-cell contact. The cytoplasm toxin immunity protein Tsi2 can neutralize Tse2 by physical interaction with the toxin, providing essential protection from toxin activity. Except for orthologues in P. aeruginosa, Tsi2 antitoxin does not share detectable sequence homology with known proteins in public databases. The mechanism underlying toxin neutralization by Tsi2 remains unknown. We report here the crystal structure of Tsi2 at 2.28 A resolution. Our structural and biophysical analyses demonstrate that the antitoxin adopts a previously unobserved superhelical conformation. Tsi2 is highly thermostable in the absence of the toxin in solution. Tsi2 assembles a dimer with 2-fold rotational symmetry, similar to that observed in other toxin-antitoxin systems. Dimerization is essential for the stable folding of Tsi2. PMID- 22310047 TI - The transition state of coupled folding and binding for a flexible beta-finger. AB - Flexible and fully disordered protein regions that fold upon binding mediate numerous protein-protein interactions. However, little is known about their mechanism of interaction. One such coupled folding and binding occurs when a flexible region of neuronal nitric oxide synthase adopts a beta-finger structure upon binding to its protein ligand, a PDZ [PSD-95 (postsynaptic density protein 95)/Discs large/ZO-1] domain from PSD-95. We have analyzed this binding reaction by protein engineering combined with kinetic experiments. Mutational destabilization of the beta-finger changed mainly the dissociation rate constant of the proteins and, to a lesser extent, the association rate constant. Thus, mutation affected late events in the coupled folding and binding reaction. Our results therefore suggest that the native binding interactions of the beta-finger are not present in the rate-limiting transition state for binding but form on the downhill side in a cooperative manner. However, by mutation, we could destabilize the beta-finger further and change the rate-limiting step such that an initial conformational change becomes rate limiting. This switch in rate-limiting step shows that multistep binding mechanisms are likely to be found among flexible and intrinsically disordered regions of proteins. PMID- 22310048 TI - Membrane protein insertion of variant MscL proteins occurs at YidC and SecYEG of Escherichia coli. AB - The mechanosensitive channel MscL in the inner membrane of Escherichia coli is a homopentameric complex involved in homeostasis when cells are exposed to hypoosmotic conditions. The E. coli MscL protein is synthesized as a polypeptide of 136 amino acid residues and uses the bacterial signal recognition particle for membrane targeting. The protein is inserted into the membrane independently of the Sec translocon but requires YidC. Depletion of YidC inhibits translocation of the protein across the membrane. Insertion of MscL occurs primarily in a proton motive force-independent manner. The hydrophilic loop region of MscL has 29 residues that include 5 charged residues. Altering the charges in the periplasmic loop of MscL affects the requirements for membrane insertion. The introduction of one, two or three negatively charged amino acids makes the insertion dependent on the electrochemical membrane potential and gradually dependent on the Sec translocon, whereas the addition of five negatively charged residues as well as the addition of three positively charged residues inhibits membrane insertion of MscL. However, we find that the mutant with three uncharged residues requires both the SecYEG complex and YidC but not SecA for membrane insertion. In vivo cross-linking data showed that the newly synthesized MscL interacts with YidC and with SecY. Therefore, the MscL mutants use a membrane insertion mechanism that involves SecYEG and YidC simultaneously. PMID- 22310049 TI - Kinetic basis for the competitive recruitment of TolB by the intrinsically disordered translocation domain of colicin E9. AB - TolB and Pal are members of the Tol-Pal system that spans the cell envelope of Gram-negative bacteria and contributes to the stability and integrity of the bacterial outer membrane (OM). Lipoylated Pal is tethered to the OM and binds the beta-propeller domain of periplasmic TolB, which, as recent evidence suggests, disengages TolB from its interaction with other components of the Tol system in the inner membrane. Antibacterial nuclease colicins such as colicin E9 (ColE9) also bind the beta-propeller domain of TolB in order to catalyze their translocation across the bacterial OM. In contrast to Pal, however, colicin binding to TolB promotes its interaction with other components of the Tol system. Here, through a series of pre-steady-state kinetic experiments utilizing fluorescence resonance energy transfer pairs within the individual protein protein complexes, we establish the kinetic basis for such 'competitive recruitment' by the TolB-binding epitope (TBE) of ColE9. Surprisingly, the 16 residue disordered ColE9 TBE associates more rapidly with TolB than Pal, a folded 13-kDa protein. Moreover, we demonstrate that calcium ions, which bind within the confines of the TolB beta-propeller domain tunnel and are known to increase the affinity of the TolB-ColE9 complex, do not exert their influence through long range electrostatic effects, as had been predicted, but through short-range effects that slow the dissociation rate of ColE9 TBE from its complex with TolB. Our study demonstrates that an intrinsically disordered protein undergoing binding-induced folding can compete effectively with a globular protein for a common target by associating more rapidly than the globular protein. PMID- 22310050 TI - Structurally similar but functionally diverse ZU5 domains in human erythrocyte ankyrin. AB - The metazoan cell membrane is highly organized. Maintaining such organization and preserving membrane integrity under different conditions are accomplished through intracellular tethering to an extensive, flexible protein network. Spectrin, the principal component of this network, is attached to the membrane through the adaptor protein ankyrin, which directly bridges the interaction between beta spectrin and membrane proteins. Ankyrins have a modular structure that includes two tandem ZU5 domains. The first domain, ZU5A, is directly responsible for binding beta-spectrin. Here, we present a structure of the tandem ZU5 repeats of human erythrocyte ankyrin. Structural and biophysical experiments show that the second ZU5 domain, ZU5B, does not participate in spectrin binding. ZU5B is structurally similar to the ZU5 domain found in the netrin receptor UNC5b supramodule, suggesting that it could interact with other domains in ankyrin. Comparison of several ZU5 domains demonstrates that the ZU5 domain represents a compact and versatile protein interaction module. PMID- 22310051 TI - Micrococcal nuclease does not substantially bias nucleosome mapping. AB - We have mapped sequence-directed nucleosome positioning on genomic DNA molecules using high-throughput sequencing. Chromatins, prepared by reconstitution with either chicken or frog histones, were separately digested to mononucleosomes using either micrococcal nuclease (MNase) or caspase-activated DNase (CAD). Both enzymes preferentially cleave internucleosomal (linker) DNA, although they do so by markedly different mechanisms. MNase has hitherto been very widely used to map nucleosomes, although concerns have been raised over its potential to introduce bias. Having identified the locations and quantified the strength of both the chicken or frog histone octamer binding sites on each DNA, the results obtained with the two enzymes were compared using a variety of criteria. Both enzymes displayed sequence specificity in their preferred cleavage sites, although the nature of this selectivity was distinct for the two enzymes. In addition, nucleosomes produced by CAD nuclease are 8-10 bp longer than those produced with MNase, with the CAD cleavage sites tending to be 4-5 bp further out from the nucleosomal dyad than the corresponding MNase cleavage sites. Despite these notable differences in cleavage behaviour, the two nucleases identified essentially equivalent patterns of nucleosome positioning sites on each of the DNAs tested, an observation that was independent of the histone type. These results indicate that biases in nucleosome positioning data collected using MNase are, under our conditions, not significant. PMID- 22310052 TI - A structural basis for reversible photoswitching of absorbance spectra in red fluorescent protein rsTagRFP. AB - rsTagRFP is the first monomeric red fluorescent protein (FP) with reversibly photoswitchable absorbance spectra. The switching is realized by irradiation of rsTagRFP with blue (440 nm) and yellow (567 nm) light, turning the protein fluorescence ON and OFF, respectively. It is perhaps the most useful probe in this color class that has yet been reported. Because of the photoswitchable absorbance, rsTagRFP can be used as an acceptor in photochromic Forster resonance energy transfer. Yellow FPs, YPet and mVenus, are demonstrated to be excellent photochromic Forster resonance energy transfer donors for the rsTagRFP acceptor in its fusion constructs. Analysis of X-ray structures has shown that photoswitching of rsTagRFP is accompanied by cis-trans isomerization and protonation/deprotonation of the chromophore, with the deprotonated cis- and protonated trans-isomers corresponding to its ON and OFF states, respectively. Unlike in other photoswitchable FPs, both conformers of rsTagRFP chromophore are essentially coplanar. Two other peculiarities of the rsTagRFP chromophore are an essentially hydrophobic environment of its p-hydroxyphenyl site and the absence of direct hydrogen bonding between this moiety and the protein scaffold. The influence of the immediate environment on rsTagRFP chromophore was probed by site directed mutagenesis. Residues Glu145 and His197 were found to participate in protonation/deprotonation of the chromophore accompanying the photoswitching of rsTagRFP fluorescence, whereas residues Met160 and Leu174 were shown to spatially restrict chromophore isomerization, favoring its radiative decay. PMID- 22310053 TI - Anterolateral mini fronto-orbito-zygomatic craniotomy via an eyebrow incision in pediatrics: technical notes and evaluation. AB - BACKGROUND: Various approaches to lesions in the anterior cranial fossa and sellar region have been described by different authors under various names which describe the extent of craniotomies. The aims of this study were to describe and retrospectively analyze and evaluate the anterolateral mini fronto-orbito zygomatic (MFOZ) approach via an eyebrow incision in treating pediatric pathologies, especially those related to the sellar region. METHOD: Between January 2003 and December 2008, 18 patients with lesions in the sellar region or the anterior corridor leading to it were operated upon via the same approach. There were 10 males and 8 females. The age ranged between 11 months and 15 years (mean 7.9 years). The pathologies were craniopharyngiomas in 6 cases, hypothalamic and chiasmal pilocytic astrocytoma in 7 and 5 miscellaneous cases including 2 pituitary adenomas, 1 extradural hematoma, hypothalamic hamartoma and 1 arachnoid cyst in the retrosellar and prepontine area. Surgery was performed from the right side in 15 cases and from the left in 3 cases. RESULTS: Total resection was achieved in 9 cases (50%), subtotal resection in 4 cases (22%), and partial resection in 5 cases (28%). Complications related to the approach like CSF rhinorrhea, supraorbital hypoesthesia and loss of upward elevation of the eyebrow were temporary. There was no mortality in this study and no significant added morbidities related to the approach. The approach has the advantages of the small cosmetic eyebrow incision and the skull base trajectory, thus reducing brain retraction and achieving the desired exposure with good outcome. CONCLUSION: The MFOZ craniotomy using an eyebrow incision in pediatric patients is safe, effective, and both suitable and convenient for treating lesions especially at the sellar region. PMID- 22310054 TI - The natural history of pelvic vein thrombosis on magnetic resonance venography after vaginal delivery. AB - OBJECTIVE: Venous thromboembolism constitutes the leading cause of direct maternal mortality in the developed world. To date, there are no studies using magnetic resonance venography (MRV) to delineate the incidence and natural history of intraluminal filling defects in the postpartum period in patients with low thrombosis risk. STUDY DESIGN: This was a prospective cohort study of women at low thrombosis risk postvaginal delivery undergoing MRV in the early postpartum period. RESULTS: In 30 eligible and consenting participants, independently adjudicated MRV, conducted on a median of postpartum day 1, identified definite thrombosis in 30% (95% confidence interval [CI], 13.6-46.4%) of study participants. All episodes of definite thrombosis were identified in the iliac and ovarian veins. Probable thrombosis was identified in an additional 27% of study participants (95% CI, 10.3-41.7%), and possible thrombosis in an additional 10% (95% CI, 0-20.7%). CONCLUSION: In this group of low-risk postpartum patients, we identified a high prevalence of definite pelvic vein intraluminal filling defects of uncertain clinical significance. This study suggests that some degree of pelvic vein intraluminal filling defect may be a normal finding after uncomplicated vaginal delivery. PMID- 22310055 TI - Androgen deprivation therapy for prostate cancer does not increase cardiovascular mortality in the long term. AB - OBJECTIVE: To determine if 6 months of neo-adjuvant androgen deprivation is associated with the long-term risk of cardiac mortality. METHODS: In the TROG 96.01 trial, 802 men with locally advanced prostate cancer were randomized to radiotherapy either alone or with 3 or 6 months of neo-adjuvant androgen deprivation therapy (NADT). Competing risk methodology was used to derive the cumulative incidence of fatal cardiac events. RESULTS: At 10 years, the cumulative incidence of fatal cardiac events for the radiation therapy alone arm was 7.54% compared to a nonstatistically significant decreased incidence of 6.44% in the 6-month NADT arm (p = 0.65). Men aged over 65 years were not at an increased risk. Additional androgen deprivation therapy given as secondary treatment at tumor progression did not confer an increased risk. CONCLUSION: These data suggest that fatal cardiac events are not more common in men receiving up to 6 months of NADT. PMID- 22310056 TI - Litterfall mercury deposition in Atlantic forest ecosystem from SE-Brazil. AB - Litterfall is believed to be the major flux of Hg to soils in forested landscapes, yet much less is known about this input on tropical environment. The Hg litterfall flux was measured during one year in Atlantic Forest fragment, located within Rio de Janeiro urban perimeter, in the Southeastern region of Brazil. The results indicated a mean annual Hg concentration of 238 +/- 52 ng g( 1) and a total annual Hg deposition of 184 +/- 8.2 MUg m(-2) y(-1). The negative correlation observed between rain precipitation and Hg concentrations is probably related to the higher photosynthetic activity observed during summer. The total Hg concentration in leaves from the most abundant species varied from 60 to 215 ng g(-1). Hg concentration showed a positive correlation with stomatal and trichomes densities. These characteristics support the hypothesis that Tropical Forest is an efficient mercury sink and litter plays a key role in Hg dynamics. PMID- 22310057 TI - A stomatal ozone flux-response relationship to assess ozone-induced yield loss of winter wheat in subtropical China. AB - Stomatal ozone flux and flux-response relationships were derived for winter wheat (Triticum aestivum L.) grown under fully open-air ozone fumigation. A stomatal conductance (g(sto)) model developed for wheat in Europe was re-parameterized. Compared to European model parameterizations, the main changes were that the VPD and radiation response functions were made less and more restrictive, respectively, and that the temperature function was omitted. The re-parameterized g(sto) model performed well with an r(2) value of 0.76. The slope and intercept of the regression between observed and predicted g(sto) were not significantly different from 1 to 0, respectively. An ozone uptake threshold of 12 nmol m(-2) s(-1) was judged most reasonable for the wheat flux-response relationship in subtropical China. Judging from both flux- and concentration-based relationships, the cultivars investigated seem to be more sensitive to ozone than European cultivars. The new flux-response relationship can be applied to ozone risk assessment in subtropical regions. PMID- 22310058 TI - Effects of herbicides on Behr's metalmark butterfly, a surrogate species for the endangered butterfly, Lange's metalmark. AB - Lange's metalmark butterfly, Apodemia mormo langei Comstock, is in danger of extinction due to loss of habitat caused by invasive exotic plants which are eliminating its food, naked stem buckwheat. Herbicides are being used to remove invasive weeds from the dunes; however, little is known about the potential effects of herbicides on butterflies. To address this concern we evaluated potential toxic effects of three herbicides on Behr's metalmark, a close relative of Lange's metalmark. First instars were exposed to recommended field rates of triclopyr, sethoxydim, and imazapyr. Life history parameters were recorded after exposure. These herbicides reduced the number of adults that emerged from pupation (24-36%). Each herbicide has a different mode of action. Therefore, we speculate that effects are due to inert ingredients or indirect effects on food plant quality. If these herbicides act the same in A. mormo langei, they may contribute to the decline of this species. PMID- 22310060 TI - Mechanical properties of H2Pc self-assembled monolayers at the single molecule level by noncontact atomic force microscopy. AB - The mechanical properties of molecular self-assembled monolayers (SAMs) play an important role in understanding the interactions between molecules in the self assembly, the interactions between molecules and substrate, and thus the formation mechanism of SAMs. Using a high-resolution noncontact atomic force microscope (NC-AFM) combined with a scanning tunneling microscope (STM), we have successfully obtained the sub-molecular resolution of a H(2)Pc self-assembled monolayer grown on a Pb(111) surface. A 2 * 2 superstructure was observed in both AFM and STM topographic images. The lateral critical force of removing a H(2)Pcmolecule from its SAM and moving a single H(2)Pc molecule on Pb(111) were measured. An oscillation of the critical force along the edge of the H(2)Pc SAM with a period of two molecular sites was observed, which can be attributed to the 2 * 2 superstructure. The lateral critical force caused by intermolecular interaction was found to be 25 pN on average and is typically two times larger than the molecule-substrate interaction. PMID- 22310059 TI - Chronic agomelatine treatment corrects the abnormalities in the circadian rhythm of motor activity and sleep/wake cycle induced by prenatal restraint stress in adult rats. AB - Agomelatine is a novel antidepressant acting as an MT1/MT2 melatonin receptor agonist/5-HT2C serotonin receptor antagonist. Because of its peculiar pharmacological profile, this drug caters the potential to correct the abnormalities of circadian rhythms associated with mood disorders, including abnormalities of the sleep/wake cycle. Here, we examined the effect of chronic agomelatine treatment on sleep architecture and circadian rhythms of motor activity using the rat model of prenatal restraint stress (PRS) as a putative 'aetiological' model of depression. PRS was delivered to the mothers during the last 10 d of pregnancy. The adult progeny ('PRS rats') showed a reduced duration of slow wave sleep, an increased duration of rapid eye movement (REM) sleep, an increased number of REM sleep events and an increase in motor activity before the beginning of the dark phase of the light/dark cycle. In addition, adult PRS rats showed an increased expression of the transcript of the primary response gene, c Fos, in the hippocampus just prior to the beginning of the dark phase. All these changes were reversed by a chronic oral treatment with agomelatine (2000 ppm in the diet). The effect of agomelatine on sleep was largely attenuated by treatment with the MT1/MT2 melatonin receptor antagonist, S22153, which caused PRS-like sleep disturbances on its own. These data provide the first evidence that agomelatine corrects sleep architecture and restores circadian homeostasis in a preclinical model of depression and supports the value of agomelatine as a novel antidepressant that resynchronizes circadian rhythms under pathological conditions. PMID- 22310061 TI - Effect of polyvinyl acetal sponge nasal packing on post-operative care of nasal polyposis patients: a randomised, controlled, partly blinded study. AB - OBJECTIVE: To compare the effects of routine nasal packing with polyvinyl acetal sponge (Merocel) versus no packing, after endoscopic sinus surgery for nasal polyposis. SUBJECTS AND METHODS: This clinical, randomised, controlled trial was performed in an academic tertiary referral centre between 2008 and 2011. Sixty patients with resistant nasal polyposis underwent endoscopic sinus surgery, and were then randomly divided into two groups: packed and non-packed. The amount of bleeding and pain in each group during pack removal was documented. RESULTS: There was no significant difference between the two groups in the outcome of surgery and complications. One patient in each group needed extra packing. In the packed group, the mean +/- standard deviation pain score on pack removal was 61 +/- 3 (using a visual analogue scale in which 0 = no pain and 100 = worst pain imaginable). CONCLUSION: This study found no significant difference between polyvinyl acetal packed and non-packed groups, following endoscopic sinus surgery for nasal polyposis. This confirms the findings of similar studies, and supports the reconsideration of routine post-operative packing in selected cases. PMID- 22310062 TI - Efficacy of the ketogenic diet: which epilepsies respond? AB - We report the efficacy of the ketogenic diet in refractory epilepsies focusing on outcomes with regard to epilepsy syndromes and etiology in children and adults with refractory epilepsy. Sixty-four consecutive children and four adults were prospectively enrolled from 2002 to 2009; seven were excluded from analysis. The classical ketogenic diet was initiated on an inpatient basis with dietary ratios ranging from 2:1 to 4:1 fat to carbohydrate and protein. Patients were classified according to syndrome and etiology using the 1989 and more recent 2010 International League Against Epilepsy (ILAE) classification systems. Responders were defined as >50% reduction in seizure frequency compared to baseline. Syndromes included symptomatic generalized (52), genetic (idiopathic) generalized (7), and focal epilepsies (2) and etiologies included structural (24), genetic (18), and unknown (19). Twenty-nine (48%) of 61 patients were responders at 3 months. Two children became seizure-free: one with focal epilepsy of unknown etiology and another with refractory childhood absence epilepsy. Responsive syndromes included migrating partial epilepsy of infancy, childhood absence epilepsy, focal epilepsy, epilepsy with myoclonic-atonic seizures, and Dravet syndrome. Children with lissencephaly and hypoxic ischemic encephalopathy had surprisingly good responses. The ketogenic diet is an effective treatment for children and adults with refractory epilepsy. The response is predicted by type of epilepsy syndrome. Accurate characterization of the electroclinical syndrome is an important factor in decisions about timing of initiation of the ketogenic diet. PMID- 22310063 TI - Proinflammatory HLA-DRB1*01-haplotype predisposes to ST-elevation myocardial infarction. AB - BACKGROUND: Major histocompatibility complex (MHC) gene region harbours haplotypes that associate with coronary artery disease (CAD). Their role in ST elevation infarction (STEMI) or on the inflammatory level is not known. METHODS: Four candidate MHC markers were analyzed by real-time quantitative PCR and constructed into haplotypes from patients with STEMI (n = 162), matched controls with no CAD (n = 319) and general population sample (n = 149). High sensitivity C reactive protein (hsCRP) was assessed in a follow-up visit from patients (n = 86) and at inclusion from other study subjects. RESULTS: The haplotype with one copy of HLA-DRB1*01, C4A, C4B but no HLA-B*35 doubled the risk of STEMI (OR = 2.15, 95%CI = 1.11-4.15, p = 0.020 for patients vs. controls, and OR = 2.26, 95%CI = 0.97-5.24, p = 0.052 for patients vs. population sample). The association between patients and controls persisted in multivariate analyses. The frequency of the haplotype was 5.86% (n = 19/324) in patients, 2.82% (n = 18/638) in controls and 2.68% (n = 8/298) in population sample. None of the individual MHC markers alone showed significant association with STEMI. In multivariate analyses, the haplotype carriers had higher hsCRP levels in patients (median 3.37 mg/L in carriers vs. 1.14 mg/L in non-carriers, p = 0.019) and in controls (median 2.90 mg/L vs. 1.21 mg/L, p = 0.009, respectively). CONCLUSION: The MHC haplotype associates with STEMI and elevated baseline hsCRP levels. The results are in concordance with previous data on non-STEMI patients, implying that a HLA-DRB1*01 -related haplotype increases the risk of CAD, possibly though increased inflammation. PMID- 22310064 TI - Polymorphisms of LTA, LGALS2, and PSMA6 genes and coronary atherosclerosis: a pathological study of 1503 consecutive autopsy cases. AB - OBJECTIVE: Recent genome-wide association studies have identified polymorphisms of lymphotoxin-alpha (LTA), galectin-2 (LGALS2), and proteasome subunit a type 6 (PSMA6) genes as genetic risk factors for myocardial infarction (MI). However, their effects on coronary atherosclerosis, an intermediate phenotype of MI, remain largely unknown. METHODS: We investigated the correlation between polymorphisms of the LTA, LGALS2, and PSMA6 genes and the severity of pathological coronary stenosis index (CSI) and MI in 1503 consecutive autopsy cases of Japanese elderly patients. RESULTS: The polymorphisms LTA rs1041981 and LGALS2 rs7291467 were associated with CSI with odds ratios of 1.54 (95% CI, 1.17 2.01; AA+CA over CC) and 1.62 (95% CI, 1.11-2.37; TT over CC+CT), respectively. PSMA6 rs1048990 was not associated with CSI. None of the SNPs was associated with MI in our sample. CONCLUSION: Our findings indicate that the LTA and LGALS2 polymorphisms affect the subclinical phenotype of the coronary artery, which predisposes to the incidence of MI. PMID- 22310065 TI - Downregulation of transforming growth factor, beta receptor 2 and Notch signaling pathway in human abdominal aortic aneurysm. AB - OBJECTIVE: Mutations in FBN1 and TGFBR2 genes are the main causative mutations identified in Marfan syndrome (MFS). The major vascular complication of MFS is aneurysm formation. Abdominal aortic aneurysm (AAA) is an acquired disease of later life of unknown etiology. The aim of this study was to examine if genetic aberrations in MFS-related genes FBN1 and TGFBR2 are present in patients with AAA. METHODS: We assessed the presence of copy number variation (CNV) in FBN1 and TGFBR2 genes in AAA biopsies from twelve patients. We also analyzed the expression of these genes in AAA biopsies compared to control biopsies from six organ donors. In addition we assessed the expression of two members of the Notch signaling pathway NOTCH3 and HEY2 as well as aortic smooth muscle cell (AoSMC) differentiation marker TAGLN in AAA and control biopsies. RESULTS: Loss of one copy (deletion) of the FBN1 exon 66 sequence and TGFBR2 exon 8 was identified in 7 (58%) and 11 (92%) of the 12 AAA biopsies. No copy number amplifications (duplications) were detected. Patients carrying TGFBR2 exon 8 deletion showed marked downregulation of this gene in AAA biopsies compared to control biopsies (0.699 vs. 1.765, p = 0.038). Notch signaling components NOTCH3 and HEY2 were markedly downregulated in AAA, while expression of the AoSMC differentiation marker TAGLN did not differ between AAA and control biopsies (0.468 vs. 0.486, p = 0.546). CONCLUSION: This study suggests an acquired impairment in TGF-beta signaling that along with downregulation of the Notch signaling pathway may contribute to the pathogenesis of AAA. PMID- 22310066 TI - Analysis of host genetic diversity and viral entry as sources of between-host variation in viral load. AB - Little is known about the factors that drive the high levels of between-host variation in pathogen burden that are frequently observed in viral infections. Here, two factors thought to impact viral load variability, host genetic diversity and stochastic processes linked with viral entry into the host, were examined. This work was conducted with the aquatic vertebrate virus, Infectious hematopoietic necrosis virus (IHNV), in its natural host, rainbow trout. It was found that in controlled in vivo infections of IHNV, a suggestive trend of reduced between-fish viral load variation was observed in a clonal population of isogenic trout compared to a genetically diverse population of out-bred trout. However, this trend was not statistically significant for any of the four viral genotypes examined, and high levels of fish-to-fish variation persisted even in the isogenic trout population. A decrease in fish-to-fish viral load variation was also observed in virus injection challenges that bypassed the host entry step, compared to fish exposed to the virus through the natural water-borne immersion route of infection. This trend was significant for three of the four virus genotypes examined and suggests host entry may play a role in viral load variability. However, high levels of viral load variation also remained in the injection challenges. Together, these results indicate that although host genetic diversity and viral entry may play some role in between-fish viral load variation, they are not major factors. Other biological and non-biological parameters that may influence viral load variation are discussed. PMID- 22310067 TI - A game theoretic model of kleptoparasitism with strategic arrivals and departures of beetles at dung pats. AB - Dung beetles Onthophagus taurus lay their eggs in brood balls within dung pats. The dung that is used must be sufficiently fresh, and so beetles must keep moving from pat to pat to find fresh dung. If another beetle finds a brood ball it will usually eat the egg inside and lay its own egg in the brood ball instead of constructing its own ball. Thus, beetles will often stay near their eggs to guard them. We model a population of beetles where the times of arrival and departure from pats are strategic choices, and investigate optimal strategies depending upon environmental conditions, which can be reduced to two key parameters, the cost of brood ball construction and the ease of finding balls to parasitise. We predict that beetles should follow one of three distinct behaviors; stay in patches for only short periods, arrive late and be purely parasitic, remain in pats for longer periods in order to guard their brood balls. Under different conditions populations can consist of the first of these types only, a combination of the first and second types, or a combination of all three types. PMID- 22310068 TI - Identifying a static nonlinear structure in a biological system using noisy, sparse data. AB - When part of a biological system cannot be investigated directly by experimentation, we face the problem of structure identification: how can we construct a model for an unknown part of a mostly known system using measurements gathered from its input and output? This problem is especially difficult to solve when the measurements available are noisy and sparse, i.e. widely and unevenly spaced in time, as is common when measuring biological quantities at the cellular level. Here we present a procedure to identify a static nonlinearity embedded between two dynamical systems using noisy, sparse measurements. To reduce the level of error caused by measurement noise, we introduce the concept of weighted sum predictability. If we make the input and output subsystems weighted-sum predictable and normalize the measurements to their weighted sum, we achieve better noise reduction than through normalizing to a loading control. We then interpolate the normalized measurements to obtain continuous input and output signals, with which we solve directly for the input-output characteristics of the unknown static nonlinearity. We demonstrate the effectiveness of this structure identification procedure by applying it to identify a model for ergosterol sensing by the proteins Sre1 and Scp1 in fission yeast. Simulations with this model produced outputs consistent with experimental observations. The techniques introduced here will provide researchers with a new tool by which biological systems can be identified and characterized. PMID- 22310069 TI - Limited memory can be beneficial for the evolution of cooperation. AB - In this study we analyze the effect of working memory capacity on the evolution of cooperation and show a case in which societies with strongly limited memory achieve higher levels of cooperation than societies with larger memory. Agents in our evolutionary model are arranged on a network and interact in a prisoner's dilemma with their neighbors. They learn from their own experience and that of their neighbors in the network about the past behavior of others and use this information when making their choices. Each agent can only process information from her last h interactions. We show that if memory (h) is too short, cooperation does not emerge in the long run. A slight increase of memory length to around 5-10 periods, though, can lead to largely cooperative societies. Longer memory, on the other hand, is detrimental to cooperation in our model. PMID- 22310070 TI - Protective effects of edaravone on experimental spinal cord injury in rats. AB - BACKGROUND: Spinal cord injury (SCI) is a leading cause of morbidity and mortality among youth and adults. Secondary injury mechanisms within the spinal cord (SC) are well known to cause deterioration after an acute impact. Free radical scavengers are among the most studied agents in animal models of SCI. Edaravone is a scavenger of hydroxyl radicals. METHODS: We aimed to measure and compare the effects of both methylprednisolone and edaravone on tissue and on serum concentrations of nitric oxide (NO), malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) activity, and tissue total antioxidant capacity (TAC) in rats with SCI. SCI was induced in four groups of Wistar albino rats by a weight-drop method. The neurological function of the rats was periodically tested. At the end of the experiment, blood samples were collected, and SC tissue samples were harvested for biochemical evaluation. RESULTS: The tissue level of NO was decreased in the edaravone treated group compared with the no-treatment group (p < 0.05). The tissue levels of SOD and GSH-Px were higher in the edaravone-treated group than in the no treatment group (p < 0.05). The serum levels of NO were lower in the edaravone treated and methylprednisolone-treated groups than in the no-treatment group (p < 0.05). The serum levels of SOD in the edaravone-treated group did not differ from those of any other group. The serum levels of MDA in the edaravone-treated and no treatment groups were higher than in the two other groups (p < 0.05). Tissue levels of MDA in the edaravone-treated group were lower than in the no-treatment group (p < 0.05). Tissue levels of TAC in the edaravone-treated group were higher than in the no-treatment and methylprednisolone-treated groups (p < 0.05). The neurological outcome scores of the animals in treatment groups did not depict any statistically significant improvement in motor functions. However, edaravone seemed to prevent further worsening of the immediate post-SCI neurological status. CONCLUSION: Our biochemical analyses indicate that edaravone is capable of blunting the increased oxidative stress that follows SCI. We show, for the first time, that edaravone enhances the TAC in SC tissue. This beneficial effect of edaravone on antioxidant status may act to minimize the secondary neurological damage that occurs during the acute phase after SCI. PMID- 22310071 TI - ABR-based newborn hearing screening with MB11 BERAphone(r) using an optimized chirp for acoustical stimulation. AB - OBJECTIVE: At our center, the Maico MB11 BERAphone((r)) device is used for newborn hearing screening based on Auditory Brainstem Responses (ABR). In 2006, an optimized chirp stimulus was implemented in the device to increase the reliability and quality of the screening method. In 2002, an automated response detection algorithm had been implemented. This study analyzes the screening results using the MB11 BERAphone((r)) device with the implemented chirp stimulus and automated response detection method. METHODS: The data presented were collected in the well-baby nursery as part of the newborn hearing screening program following a two stage screening protocol. To focus the study on the typical routine screening, data from at-risk babies were not included. Overall, data from 6866 babies (3604 males and 3262 females) screened from March 2006 to April 2011 were analyzed in this study. RESULTS: Out of the 6866 babies screened, 6607 passed bilaterally prior to hospital discharge (defined as 1st stage in this hearing screening program). Therefore, the pre-discharge pass rate of the hearing screening with the MB11 BERAphone((r)) device was 96.2%. The resulting referral rate was 3.8%. The median test time per ear (excluding time for preparation and data reporting) was 28s with a range of 15-112s (5-95th percentile). The number of infants referred for 2nd stage, post-discharge re-screening was 259. Of this group, 71 passed bilaterally and 188 failed the re-screening in one or both ears. Therefore, including both the pre-discharge and post-discharge screening results, the bilateral pass rate was 97.3% and 2.7% were referred for diagnostic evaluation. Diagnostic testing was performed on all of the 188 infants who were referred. Results showed that 47 of these babies had hearing loss. This equates to a positive predictive value for a refer result of 25%. The observed prevalence of hearing impairment in our population was 0.684%. Diagnostic results for 141 of the referred newborns proved that they had normal hearing. That is, 141 out of 6866 newborns had a false-positive result with the MB11 BERAphone((r)) screening. Therefore, the device had a specificity of 97.9%. During the time period of this study, no baby who passed the hearing screening was later found to have hearing impairment, suggesting a sensitivity of 100%. However, due to the limited number of newborns and the short time period after screening for the more recently screened babies, a reliable estimate of the sensitivity cannot be yet made from our program statistics. The theoretical sensitivity of the MB 11 device is 99.9%. CONCLUSIONS: The Maico MB11 BERAphone((r)) is a reliable device for auditory brainstem response newborn hearing screening and it provides results within a very short time. Due to the implemented method for automatic detection of ABR, the use of the device does not require an experienced examiner, allowing it to be used by trained technicians in locations outside the department of audiology such as the well-baby nursery. PMID- 22310072 TI - Maternal breastfeeding, parafunctional oral habits and malocclusion in adolescents: a multivariate analysis. AB - OBJECTIVE: Malocclusion may result in esthetic impairment and functional disorders such as bad chewing, speech and swallowing, with a negative impact on quality of life. There is uncertainty regarding the effects of breastfeeding on dentofacial malocclusions. The purpose of the study was to evaluate the relationship between maternal breastfeeding and dental malocclusions and facial characteristics in adolescents with permanent dentition. METHODS: Probabilistic sampling of 2060 12- to 15-year-old students in a cross-sectional study was used. Malocclusion, as defined by Angle, and facial characteristics were the dependent variables. The duration of breastfeeding was the main independent variable. Other covariates were tested as effect modifiers or confounders. The associations were estimated using the odds ratio (OR) in multinomial logistic regression analysis (alpha=5%). RESULTS: There was an association between a short duration of breastfeeding (less than 6 months) and Angle class II (OR=3.14; 95% CI: 1.28 7.66) and class III (OR=2.78; 95% CI: 1.21-6.36) malocclusion only in students with a prolonged history of bruxism. A higher occurrence of severe convex profile (OR=3.4; 95% CI: 0.63-18.26) and a lower occurrence of cancave profile (OR=0.43; 95% CI: 0.21-0.88) were also observed only among adolescents who had been breastfed for a short period and exposed to a long periods of mouth breathing. CONCLUSIONS: These findings support the hypothesis that breastfeeding alone seems not to be directly associated with malocclusions, but it may have a synergetic effect with parafunctional oral habits on the development of occlusofacial problems. It is recommended that deleterious oral habits be avoided, especially by children who were breast-fed for less than 6 months. PMID- 22310073 TI - Detection, molecular characterization and phylogenetic analysis of full-length equine infectious anemia (EIAV) gag genes isolated from Shackleford Banks wild horses. AB - The genetically distinct wild horse herds inhabiting Shackleford Banks, North Carolina are probably the direct descendents of Spanish stock abandoned after failed attempts to settle mid-Atlantic coastal regions of North America in the Sixteenth Century. In a 1996 island survey, 41% of the gathered horses were discovered seropositive for Equine Infectious Anemia Virus (EIAV) with additional cases identified in 1997 and 1998. As a result of their unique genetic heritage, EIAV seropositive individuals identified in the two latter surveys were transferred to a quarantine facility on the mainland. In September 2008 two of the horses SB1 and SB2 after 10 and 11 years in quarantine respectively, developed clinical signs of EIA. In the case of SB2 these were so severe that the only humane option was euthanasia. Although SB1, survived it experienced a second clinical episode one month later. In May 2009, a third horse in quarantine, SB3, developed extremely severe clinical EIA and was euthanized. This demonstrates naturally infected long-term inapparent carriers can experience recrudescence of very severe disease many years after initial exposure to EIAV. Phylogenetic analysis of complete EIAV gag gene sequences obtained from each of three Shackleford horses demonstrated they were infected with very closely related viruses. Although these were distinguishable from all other strains examined, they belong to a monophyletic group comprising almost exclusively of New World isolates that is distinct from a number of recently characterized Central European EIAV strains. PMID- 22310074 TI - Bacterial composition and activity determines host gene-expression responses in gnotobiotic Atlantic cod (Gadus morhua) larvae. AB - In this study the effects of different live versus dead bacteria on the survival and gene-expression patterns in Atlantic cod (Gadus morhua) larvae were examined. Seventeen different gnotobiotic conditions were tested in a 5-day experiment, and the effects of these conditions on the expression of selected genes involved in immune response, xenobiotic breakdown and nutrition (C3, Gpx, Cyp1a1 and Fdps) were investigated. For some of the conditions where dead bacteria were added, we observed significantly higher survival compared to the axenic control. Microbial specificity of host-responses was observed for all four genes, for both live and dead bacteria, although expression of Gpx and Fdps was more influenced by active bacteria. Live bacteria generally resulted in higher transcript levels of all the genes investigated, indicating that these host-responses are partly dependent on microbial activity, and not just due to interactions with bacteria as particles. The observed microbial specificity toward dead bacteria highlights the need to take into account the role of bacterial components when investigating host microbe relationships. PMID- 22310075 TI - High-resolution imaging of C60 molecules using tuning-fork-based non-contact atomic force microscopy. AB - Recent advances in non-contact atomic force microscopy (nc-AFM) have led to the possibility of achieving unprecedented resolution within molecular structures, accomplished by probing short-range repulsive interaction forces. Here we investigate C(60) molecules adsorbed on KBr(111) and Cu(111) by tuning-fork-based nc-AFM. First, measurements of C(60) deposited on KBr(001) were conducted in cryogenic conditions revealing highly resolved nc-AFM images of the self assembly. Using constant-frequency shift mode as well as three-dimensional spectroscopic measurements, we observe that the relatively weak molecule substrate interaction generally leads to the disruption of molecular assembled structures when the tip is probing the short-range force regime. This particular issue hindered us in resolving the chemical structure of this molecule on the KBr surface. To obtain a better anchoring of C(60) molecules, nc-AFM measurements were performed on Cu(111). Sub-molecular resolutions within the molecules was achieved which allowed a direct and unambiguous visualization of their orientations on the supporting substrate. Furthermore, three-dimensional spectroscopic measurements of simultaneous force and current have been performed above the single molecules giving information of the C(60) molecular orientation as well as its local conductivity. We further discuss the different imaging modes in nc-AFM such as constant-frequency shift nc-AFM, constant-height nc-AFM and constant-current nc-AFM as well as three-dimensional spectroscopic measurement (3D-DFS) employed to achieve such resolution at the sub-molecular scale. PMID- 22310077 TI - Peripheral exudative hemorrhagic chorioretinopathy: polypoidal choroidal vasculopathy and hemodynamic modifications. AB - PURPOSE: To investigate choroidal vascular abnormalities in peripheral exudative hemorrhagic chorioretinopathy, using dynamic ultrawide-field fluorescein angiography (FA) and indocyanine green angiography (ICGA). DESIGN: Prospective observational case series. METHODS: This institutional study comprised a consecutive series of 40 patients (48 eyes) with peripheral exudative hemorrhagic chorioretinopathy. Choroidal vascular abnormalities were assessed with dynamic ultrawide-field (150-degree) FA and ICGA, using the Staurenghi 230 SLO Retina Lens and the Heidelberg scanning laser ophthalmoscope. The main outcome measures were morphologic descriptions of structural vascular abnormalities and choroidal hemodynamics (comparison with 30 normal eyes). RESULTS: The peripheral mass lesions were highly exudative and hemorrhagic, and usually associated with a pigment epithelium detachment. FA revealed nonspecific alterations corresponding to the visible fundoscopic changes (window defects, blockage, staining), but no neovascular membrane. However, despite frequent masking, ICGA showed hyperfluorescent polyp-like structures in the choroid of the lesion area in 33 eyes (69%) and an abnormal choroidal vascular network in 24 eyes (50%). The abnormal choroidal vascular network filled in the arterial or early venous phase, while the polyp-like structures filled some seconds later. Optical coherence tomography revealed the typical dome-shaped elevation of the pigment epithelium over the vascular polyps. Peripheral choriocapillaris closure was observed as well as dilated shunting vessels. CONCLUSION: Peripheral exudative hemorrhagic chorioretinopathy shares many characteristics (polyp-like choroidal telangiectases, abnormal choroidal vascular networks, exudative and hemorrhagic presentation) with polypoidal choroidal vasculopathy. Clarification of the precise role of these abnormalities requires further studies. PMID- 22310078 TI - Pharmacokinetic study of vitreous and serum concentrations of triamcinolone acetonide after posterior sub-tenon's injection. AB - PURPOSE: To compare a theoretical pharmacokinetic model of triamcinolone acetonide after posterior sub-Tenon's injection with experimental serum and undiluted vitreous triamcinolone acetonide concentrations obtained during pars plana vitrectomy. DESIGN: Clinical-practice, prospective, interventional case series study. METHODS: This study compared computer-modeled triamcinolone acetonide diffusion after posterior sub-Tenon's injection with triamcinolone acetonide levels in experimental undiluted vitreous and serum samples from 57 patients undergoing vitrectomy assessed via mass spectrometry and high-pressure liquid chromatography. At least 5 pairs of samples were collected at each of 7 time points (1 day, 3 days, and 1, 2, 3, 4, and 8 weeks) after triamcinolone acetonide injection, with 6 controls without injection. Cortisol levels were measured in 31 sets of samples. RESULTS: The theoretical model predicted that triamcinolone acetonide levels in systemic blood, vitreous, and choroidal extracellular matrix would plateau after 3 days at 15 ng/mL, 227 ng/mL and 2230 ng/mL, respectively. Experimental vitreous levels of triamcinolone peaked at 111 ng/mL at day 1, then reached a plateau in the range 15 to 25 ng/mL, while serum triamcinolone levels peaked at day 3 near 35 ng/mL and plateaued near 2 to 8 ng/mL. Serum triamcinolone and cortisol levels were inversely correlated (Spearman -0.42, P = .02). CONCLUSIONS: The theoretical model predicts efficient delivery of triamcinolone acetonide from the posterior sub-Tenon's space to the extracellular choroidal matrix. The experimental findings demonstrate low levels of serum triamcinolone that alter systemic cortisol levels and higher vitreous levels lasting at least 1 month. Both assessments support trans-scleral delivery of posterior sub-Tenon's triamcinolone. PMID- 22310079 TI - Characteristics of peripapillary retinal nerve fiber layer in preterm children. AB - PURPOSE: To examine quantitatively characteristics of the peripapillary retinal nerve fiber layer (RNFL) in preterm children using Fourier-domain optical coherence tomography (FD-OCT). DESIGN: Prospective cross-sectional study. METHODS: A 3-mm high-resolution FD-OCT peripapillary RNFL circular scan centered on the optic disc was obtained from right eyes of 25 preterm children (10.6 +/- 3.7 years old, 8 preterm and 17 with regressed retinopathy of prematurity with normal-appearing posterior poles) and 54 full-term controls (9.8 +/- 3.2 years old). Images were analyzed using Spectralis FD-OCT software to obtain average thickness measurements for 6 sectors (temporal superior, temporal, temporal inferior, nasal inferior, nasal, nasal superior), and the global average. RESULTS: The RNFL global average for preterm children was 8% thinner than for full-term controls. In the preterm group, peripapillary RNFL thickness on the temporal side of the disc was 6% thicker than in full-term controls, while all other peripapillary RNFL sectors were 9% to 13% thinner. In the preterm group, temporal sector peripapillary RNFL thickness was correlated with gestational age (r = -0.47, P < .001), with foveal center total thickness (r = 0.48, P = .008, 1 tailed), and with visual acuity (r = 0.42; P = .026, 1-tailed). CONCLUSIONS: The significantly thinner RNFL global average for preterm children suggests that prematurity is associated with subclinical optic nerve hypoplasia. Significant correlations between temporal sector RNFL thickness and both the foveal thickness and visual acuity suggest that the peripapillary RNFL is related to abnormalities in macular development as a result of preterm birth. PMID- 22310080 TI - Relationship between corneal biomechanical properties, central corneal thickness, and intraocular pressure across the spectrum of glaucoma. AB - PURPOSE: To evaluate corneal biomechanical properties across the glaucoma spectrum and study the relationship between these measurements and intraocular pressure measured by Goldmann applanation tonometry (GAT-IOP) and central corneal thickness (CCT). DESIGN: Prospective cross-sectional study. METHODS: SETTING: Tertiary-care teaching institute. STUDY POPULATION: A total of 323 eyes of 323 participants (71 normal, 101 glaucoma suspect [GS], 38 ocular hypertension [OHT], 59 primary angle-closure disease [PACD], 36 primary open-angle glaucoma [POAG], and 18 normal-tension glaucoma [NTG]) who had received no ophthalmic treatment. OBSERVATION PROCEDURES: Corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated IOP (IOPcc), and Goldmann-correlated IOP (IOPg) measured by the Ocular Response Analyzer (ORA). GAT-IOP and CCT recorded in all subjects. MAIN OUTCOME MEASURES: Regression analysis used to determine the relationship between GAT-IOP, CCT, age, CRF, and CH. Bland-Altman plots used to assess agreement between IOP measured by GAT and the ORA (IOPg). RESULTS: CH measurements were significantly less in POAG and NTG compared to normal subjects (P = .034 and P = .030 respectively), regardless of the IOP. The CRF was significantly less in NTG and maximum in POAG and OHT. Regression analysis with CH as dependant variable showed significant association with GAT-IOP and CRF (P < .001) but not CCT, persisting on multivariate analysis (adjusted R(2) = 0.483). GAT-IOP correlated strongly with Goldmann-correlated IOP on the ORA (IOPg) (r = 0.82; P < .001), but limits of agreement between the measurements were poor. CONCLUSIONS: CH and CRF may constitute a pressure-independent risk factor for glaucoma. CRF appears to influence GAT-IOP measurements more than simple geometric thickness measured by CCT. However, IOP measurements from the ORA are not interchangeable with, and are unlikely to replace, Goldmann applanation tonometry at the present time. PMID- 22310081 TI - Clinical evaluation of three incision size-dependent phacoemulsification systems. AB - PURPOSE: To compare the outcomes of cataract surgery performed with 3 incision size-dependent phacoemulsification groups (1.8, 2.2, and 3.0 mm). DESIGN: Prospective randomized comparative study. METHODS: One hundred twenty eyes of 120 patients with age-related cataract (grades 2 to 4) were categorized according to the Lens Opacities Classification System III. Eligible subjects were randomly assigned to 3 surgical groups using coaxial phacoemulsification through 3 clear corneal incision sizes (1.8, 2.2, and 3.0 mm). Different intraoperative and postoperative outcome measures were obtained, with corneal incision size and surgically induced astigmatism as the main clinical outcomes. RESULTS: There were no statistically significant differences in most of the intraoperative and postoperative outcome measures among the 3 groups. However, the mean cord length of the clear corneal incision was increased in each group after surgery. The mean maximal clear corneal incision thickness in the 1.8-mm group was significantly greater than for the other groups at 1 month. The mean surgically induced astigmatism in the 1.8- and 2.2-mm groups was significantly less than that in the 3.0-mm group after 1 month, without significant difference between the 1.8- and 2.2-mm groups. CONCLUSIONS: With appropriate equipment, smaller incisions may result in less astigmatism, but the particular system used will influence incision stress and wound integrity, and may thus limit the reduction in incision size and astigmatism that is achievable. PMID- 22310082 TI - Infrared imaging and optical coherence tomography reveal early-stage astrocytic hamartomas not detectable by fundoscopy. AB - PURPOSE: To describe and correlate the features of astrocytic hamartomas using multimodal imaging. DESIGN: Prospective, noncomparative, observational case series. METHODS: This was a single-center study of 4 patients (8 eyes) with tuberous sclerosis complex. A complete ophthalmologic examination, fundus photography, fundus autofluorescence (FAF), infrared imaging, and spectral-domain optical coherence tomography (SD-OCT) were performed for each patient. Images from each modality were analyzed and compared. RESULTS: In 2 patients, infrared imaging and SD-OCT detected occult retinal astrocytic hamartomas that were not observed on clinical examination or color fundus photography. FAF demonstrated the greatest contrast between lesions and surrounding retina but failed to identify 1 occult lesion that was detected with infrared imaging and SD-OCT. SD OCT revealed lesions arising from the retinal nerve fiber layer with overlying vitreous adhesions, hyperreflective dots, and optically empty spaces at all depths of the tumor. Hamartomas were hyporeflective on infrared imaging and hypoautofluorescent on FAF. FAF of some lesions demonstrated hyperautofluorescent spots. CONCLUSIONS: Infrared imaging and SD-OCT aid in the detection of astrocytic hamartomas that are not visible on clinical examination or color fundus photography. SD-OCT enhances visualization of structural details. FAF is a useful adjunctive test to obtain greater contrast between lesions and surrounding retina. The ability to monitor structural changes over time in astrocytic hamartomas using SD-OCT may be beneficial for monitoring the success of systemic chemotherapy in the treatment of various tuberous sclerosis tumors. PMID- 22310076 TI - Incidence of cytomegalovirus retinitis in the era of highly active antiretroviral therapy. AB - PURPOSE: To estimate the incidence of cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART) and to characterize the factors associated with increased risk of CMV retinitis. DESIGN: Prospective cohort study. METHODS: A total of 1600 participants with acquired immunodeficiency syndrome (AIDS) but without CMV retinitis at enrollment who completed at least 1 follow-up visit in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) were seen every 6 months to obtain disease and treatment history, ophthalmic examination, and laboratory testing. Incidence of CMV retinitis and risk factors for incident CMV retinitis were assessed. RESULTS: The incidence rate of CMV retinitis in individuals with AIDS was 0.36/100 person-years (PY) based upon 29 incident cases during 8134 PY of follow-up. The rate was higher for those with a CD4+ T cell count at the immediately prior visit below 50 cells/MUL (3.89/100 PY, P < .01), whereas only 1 individual with a CD4+ T cell count of 50 to 99 cells/MUL and 2 individuals with a CD4+ T cell count >100 cells/MUL developed CMV retinitis. Having a CD4+ T cell count below 50 cells/MUL at the clinical visit prior to CMV retinitis evaluation was the single most important risk factor (HR: 136, 95% CI: 30 to 605, P < .0001) for developing retinitis. CONCLUSIONS: Patients with AIDS, especially those with severely compromised immune systems, remain at risk for developing CMV retinitis in the HAART era, although the incidence rate is reduced from that observed in the pre-HAART era. PMID- 22310083 TI - Relationship between choroidal thickness and choroidal circulation in healthy young subjects. AB - PURPOSE: To investigate the relationship between the choroidal thickness and choroidal blood flow in healthy young subjects. DESIGN: Retrospective, cross sectional study. METHODS: We examined 25 eyes of 25 healthy young Japanese subjects. The subfoveal choroidal thickness was measured by enhanced depth imaging optical coherence tomography (EDI-OCT). The total choroidal blood flow and subfoveal choroidal blood flow were evaluated by pulsatile ocular blood flow using Langham OBF computerized tonometry and the choroidal blood flow using laser Doppler flowmetry. The refractive error, intraocular pressure, and axial length were also measured. RESULTS: The mean refractive error was -3.4 +/- 3.1 diopters, mean intraocular pressure 15.3 +/- 1.7 mm Hg, and axial length 25.4 +/- 2.0 mm. The subfoveal choroidal thickness was correlated positively (r = 0.785, P < .01) with the refractive error and negatively (r = -0.735, P < .001) with the axial length. No significant correlation was found between the subfoveal choroidal thickness and the pulsatile ocular blood flow or choroidal blood flow. CONCLUSION: Our results suggested that there were no significant correlations between the subfoveal choroidal thickness and the total choroidal blood flow and the subfoveal choroidal blood flow in healthy young subjects; however, decreased subfoveal choroidal thickness was associated with decreased refractive error and axial length. PMID- 22310084 TI - Topical FK962 facilitates axonal regeneration and recovery of corneal sensitivity after flap surgery in rabbits. AB - PURPOSE: To test if the drug FK962 (N-(1-acetylpiperidin-4-yl)-4-fluorobenzamide) facilitates axonal elongation and recovery of corneal sensitivity after creation of a corneal flap in rabbits. DESIGN: Animal study. METHODS: Primary cultures of rabbit trigeminal ganglion cells were used to test if FK962 promoted nerve elongation in vitro. A 130 MUm-thick*8.6 mm-diameter flap was created in rabbit corneas where topical 10(-6) M FK962 was administered 4 times daily. After treatment of 7 days, corneal mechanical sensitivity was measured using a Cochet Bonnet esthesiometer. Whole-mount corneal sections were prepared, sensory nerve axons were stained with antibody for neurofilament, and axonal elongation from transected nerve termini were scored using standardized criteria. Ocular pharmacokinetics modeling was used to predict permeation of topical FK962 into cornea. RESULTS: FK962 accelerated sprouting and elongation of neurites in cultured neuronal cells from rabbit trigeminal ganglia. In the in vivo rabbit model, distal axons from transected nerve termini in corneas disappeared soon after flap surgery; but with time, axons regenerated and elongated. Topical application of 10(-6) M FK962 for 7 days significantly enhanced axonal elongation and increased corneal sensitivity. Increased corneal sensitivity was directly and significantly correlated with axonal elongation, suggesting functional enhancement of re-innervation by FK962. CONCLUSIONS: Results from a rabbit model of laser in situ keratomileusis (LASIK) surgery showed that topical FK962 facilitated corneal re-innervation leading to recovery of sensitivity. Results suggested that topical application of FK962 might decrease complications in patients after LASIK surgery. PMID- 22310085 TI - Early postoperative hypotony and ciliochoroidal detachment after microincision vitrectomy surgery. AB - PURPOSE: To determine the relationship between a ciliochoroidal detachment and intraocular pressure (IOP) after microincision vitrectomy surgery (MIVS). DESIGN: Prospective, consecutive, observational case series. METHODS: Thirty eyes of 30 patients with an epiretinal membrane that underwent MIVS were prospectively studied. The intraocular pressure (IOP) was measured before 3-port MIVS, and at 1 minute, 1 and 3 hours, and at 1 day postoperatively. All of the 90 sclerotomies were examined by swept source optical coherence tomography to assess the wound and presence of a ciliochoroidal detachment at 3 hours and at 1 day postoperatively. The mean IOP and closure rate of the sclerotomies were compared between eyes with and without a ciliochoroidal detachment. The correlation between the presence of ciliochoroidal detachment and postoperative IOP was determined. RESULTS: The incidence of ciliochoroidal detachment was 63.3% (19 eyes) during the 1-day observation period. The mean postoperative IOPs were significantly lower than the preoperative IOPs in eyes with a ciliochoroidal detachment (P < .05). The mean postoperative IOPs were significantly higher in eyes without a ciliochoroidal detachment than in eyes with a ciliochoroidal detachment (P < .05). The incidence of open sclerotomies was significantly higher in eyes with a ciliochoroidal detachment than in eyes without a ciliochoroidal detachment at 3 hours postoperatively (P = .03). CONCLUSIONS: A shallow ciliochoroidal detachment develops in 63.3% of eyes after MIVS. Hypotony at the early postoperative period may be a risk factor for a ciliochoroidal detachment. PMID- 22310086 TI - Randomized clinical trial of the efficacy and safety of preservative-free tafluprost and timolol in patients with open-angle glaucoma or ocular hypertension. AB - PURPOSE: To compare the efficacy and safety of tafluprost, a preservative-free (PF) prostaglandin analogue, with PF timolol in patients with open-angle glaucoma or ocular hypertension. DESIGN: Randomized, double-masked, multicenter clinical trial. METHODS: After discontinuation and washout of existing ocular hypotensive treatment, patients who had intraocular pressure (IOP) >=23 and <=36 mm Hg in at least 1 eye at the 08:00 hour time point were randomized 1:1 to 12 weeks of treatment with either PF tafluprost 0.0015% or PF timolol 0.5%. IOP was measured 3 times during the day (08:00, 10:00, 16:00 hours) at baseline and at weeks 2, 6, and 12. It was hypothesized that PF tafluprost would be noninferior to PF timolol over 12 weeks with regard to change from baseline IOP. The trial was powered for a noninferiority margin of 1.5 mm Hg at each of the 9 time points assessed. RESULTS: A total of 643 patients were randomized and 618 completed (PF tafluprost = 306, PF timolol = 312). IOPs at the 3 time points assessed during the baseline visit ranged from 23.8 to 26.1 mm Hg in the PF tafluprost group and 23.5 to 26.0 mm Hg in the PF timolol group. IOPs at the 3 time points assessed during the 12 week visit ranged from 17.4 to 18.6 mm Hg for PF tafluprost and 17.9 to 18.5 mm Hg for PF timolol. At all 9 time points, the upper limits of the 2-sided 95% confidence intervals for the difference between treatments in IOP lowering were less than the prespecified noninferiority margin. Similar percentages of PF tafluprost and PF timolol patients reported ocular pain/stinging/irritation (4.4% vs 4.6%) and pruritus (2.5% vs 1.5%). The percentages of PF tafluprost and PF timolol patients reporting conjunctival hyperemia were 4.4% vs 1.2% (nominal P = .016). CONCLUSIONS: The IOP-lowering effect of PF tafluprost was noninferior to that of PF timolol. PF tafluprost is an efficacious and generally well-tolerated ocular hypotensive agent. PMID- 22310087 TI - Cholesteatoma surgery in children: 10-year retrospective review. AB - OBJECTIVE: To review outcomes following paediatric cholesteatoma surgery performed between 1999 and 2009 in a tertiary paediatric ENT unit. STUDY DESIGN: Retrospective case note review. RESULTS: A total of 137 mastoid procedures were recorded. Fifty-four per cent of children were observed to have disease involving the entire middle-ear cleft and mastoid complex. The revision rate was 25 per cent. Time to recurrence was one to three years in 17 patients, three to six years in five patients, and six to nine years in three cases. Eight of 25 revision cases demonstrated spontaneous improvement in air conduction thresholds following primary surgery. A high facial ridge and inadequate meatoplasty correlated highly with disease recurrence. CONCLUSION: Children tend to present with aggressive disease. Disease extent and ossicular chain involvement are associated with a higher risk of recurrent disease. Spontaneous improvement in hearing thresholds following cholesteatoma surgery should alert the clinician to recurrent disease. PMID- 22310088 TI - Efficacy, safety, and potential biomarkers of thalidomide plus metronomic chemotherapy for advanced hepatocellular carcinoma. AB - OBJECTIVES: Thalidomide has been shown to have antitumor activity in some patients with advanced hepatocellular carcinoma (HCC). We initiated a phase II study to determine the safety and efficacy of adding metronomic chemotherapy to thalidomide as first-line therapy. METHODS: This open- labeled, single-arm, multicentered, investigator-initiated study enrolled patients with treatment naive advanced HCC not amenable to locoregional therapies. Treatment included oral thalidomide (100 mg twice daily) and tegafur/uracil [125 mg/m(2) (based on tegafur) twice daily]. Tumor assessment was performed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. Pretreatment plasma levels of angiogenesis factors were correlated with patient outcomes. RESULTS: Forty-three patients were included. Sixteen (37%) patients had a Cancer of the Liver Italian Program (CLIP) score of 4, and 31 (72%) patients had chronic hepatitis B virus infection. The objective response rate was 9%, and the disease stabilization rate was 33%. The median progression-free survival was 1.9 months (95% CI 1.7-2.1 months), and the median OS was 4.6 months (95% CI 2.3-6.9 months). Treatment was generally tolerable. High baseline plasma levels of interleukin (IL)-6 and IL-8 were adversely correlated with patient survivals. CONCLUSIONS: The combination of thalidomide and tegafur/uracil was safe and demonstrated modest activity in patients with advanced HCC. PMID- 22310089 TI - Highly potent delivery method of gp160 envelope vaccine combining lentivirus-like particles and DNA electrotransfer. AB - Particulate antigen assemblies in the nanometer range and DNA plasmids are particularly interesting for designing vaccines. We hypothesised that a combination of these approaches could result in a new delivery method of gp160 envelope HIV-1 vaccine which could combine the potency of virus-like particles (VLPs) and the simplicity of use of DNA vaccines. Characterisation of lentivirus like particles (lentiVLPs) by western blot, dynamic light scattering and electron microscopy revealed that their protein pattern, size and structure make them promising candidates for HIV-1 vaccines. Although all particles were similar with regard to size and distribution, they clearly differed in p24 capsid protein content suggesting that Rev may be required for particle maturation and Gag processing. In vivo, lentiVLP pseudotyping with the gp160 envelope or with a combination of gp160 and VSV-G envelopes did not influence the magnitude of the immune response but the combination of lentiVLPs with Alum adjuvant resulted in a more potent response. Interestingly, the strongest immune response was obtained when plasmids encoding lentiVLPs were co-delivered to mice muscles by electrotransfer, suggesting that lentiVLPs were efficiently produced in vivo or the packaging genes mediate an adjuvant effect. DNA electrotransfer of plasmids encoding lentivirus-like particles offers many advantages and appears therefore as a promising delivery method of HIV-1 vaccines. PMID- 22310090 TI - The functional rating index: reliability and validity of the Persian language version in patients with neck pain. AB - STUDY DESIGN: Psychometric testing of the Persian Functional Rating Index (PFRI). OBJECTIVE: To determine the reliability and validity of the PFRI in Persian speaking subjects with neck pain (NP). SUMMARY OF BACKGROUND DATA: The Functional Rating Index is a self-report questionnaire that can be used for patients with back pain or NP. The PFRI has been recently validated in patients with low back pain, whereas it is not validated in patients with NP. METHODS: One hundred patients with NP, mean age of 42 years, participated in the study; 50 patients agreed to be tested on 2 occasions during a 7-day interval for the reliability phase of the study. A visual analogue scale, the Neck Disability Index, and the Neck Pain and Disability Scale were also completed to assess validity. Fifty healthy subjects completed the PFRI for discriminative validity. RESULTS: Floor and ceiling effects were not observed. Independent t test showed a statistically significant difference in PFRI total scores between patients and healthy subjects supporting the discriminative validity of the PFRI (P < 0.001). PFRI and visual analogue scale demonstrated concurrent criterion validity, with Pearson correlation coefficients of 0.75 for test and 0.70 for retest. Construct validity was supported by a significant Pearson correlation between the PFRI and the Neck Disability Index (r = 0.72, P < 0.0001) and between the PFRI and the Neck Pain and Disability Scale (r = 0.63, P < 0.0001). Factor analysis revealed a 2-factor solution, which jointly accounted for 64.75% of the total variance. Additional factor analysis suggested 8-item PFRI as a unidimensional functional instrument for patients with NP. Internal consistency for the PFRI was high. (Cronbach alpha coefficients were 0.88 for test, 0.89 for retest, and 0.89 for 8-item PFRI.) Reproducibility assessed by test-retest reliability was excellent (intraclass correlation coefficient [ICC](agreement) of 0.96, P < 0.0001). CONCLUSION: The PFRI is valid and reliable for use in a Persian-speaking population with NP. PMID- 22310092 TI - Topographic anatomy of the posterior ramus of thoracic spinal nerve and surrounding structures. AB - STUDY DESIGN: Cadaver dissection. OBJECTIVE: To examine the potential points of spinal nerve entrapment and the articular branches in the thoracic spine. SUMMARY OF BACKGROUND DATA: Despite many cadaver studies focused on the cervical and lumbar spinal nerves, detailed anatomy of the thoracic nerve branches is missing from the viewpoint of painful neuropathy on the thoracic region. METHODS: A total of 120 pairs of thoracic spinal nerves out of 10 donated cadavers were dissected. Detailed anatomy of the posterior ramus and medial/lateral branches and their fine branches in the entire thoracic region was investigated by both macroscopic and stereomicroscopic dissections. RESULTS: The posterior ramus of the thoracic nerve passed through the narrow space between the bony structures and adjacent fibrous tissue. It is sent to the first branch, which is called "the descending branch," before bifurcating into medial and lateral branches. The medial branch runs posterolaterally, then turns medially along the edge of multifidus, and passes between that and semispinalis, whereas the lateral branch runs underneath the intertransverse ligament. Both medial and lateral cutaneous branches penetrated the thoracolumbar fascia, and the medial cutaneous branch penetrated the tendinous portion of back muscles. CONCLUSION: Several points might be listed as potential sites of entrapment along the course of the posterior ramus of the thoracic nerve and its branches, leading to the cause of thoracic back pain. In addition, the articular branch entering the facet (zygapophyseal) joint originated from the descending branch, which was the first branch of the posterior ramus. PMID- 22310093 TI - Female patients' and parents' assessment of deformity- and brace-related stress in the conservative treatment of adolescent idiopathic scoliosis. AB - STUDY DESIGN: A cross-sectional analysis of parents' and patients' perceptions of deformity- and brace-related stress regarding conservative treatment of adolescent idiopathic scoliosis. OBJECTIVE: The purpose of this study was to determine the agreement between patients' and parents' assessments of emotional stress and to compare these assessments with radiographical measurements of spinal deformity. SUMMARY OF BACKGROUND DATA: Conservative treatment in patients with scoliosis may cause emotional stress. To our knowledge, no group has ever reported patient and parental estimation of stress related to wearing a brace and spinal deformity in girls with adolescent idiopathic scoliosis. METHODS: Sixty three pairs of parents and girls with adolescent idiopathic scoliosis treated with a Cheneau brace were separately asked to complete the Bad Sobberheim Stress Questionnaire-Deformity and the Bad Sobberheim Stress Questionnaire-Brace. The age range of the patients was from 10 to 17 years. Patients were assessed at a mean of 14.12 (SD, 10.99) months after the start of the conservative treatment. RESULTS: Patients thought that a moderate level of stress was connected with conservative treatment; however, the stress level, related to perceived trunk deformation, was low. From the parents' perspective, patients experienced a moderate level of stress during conservative treatment and related to spinal deformity. The study groups differ in their perception of stress levels due to body disfigurement but not during the conservative treatment. Parent-patient stress-level disparities were not related to body mass index, age of the patient, brace application, and radiographical measurements of spinal deformity. CONCLUSION: Patients and parents perceive the emotional stress related to brace treatment in the same way; however, parents overestimate the assessment of stress levels related to body deformity. From the perspective of patients and parents, brace wearing increased the level of stress induced by the deformity alone. Complete assessment of conservative treatment should include evaluation of emotional stress from the perspective of patients and parents. PMID- 22310094 TI - Guidelines on low back pain disability: interprofessional comparison of use between general practitioners, occupational therapists, and physiotherapists. AB - STUDY DESIGN: Individual semistructured qualitative interviews. OBJECTIVE: To evaluate barriers to use of management recommendations, aimed at preventing low back pain (LBP) disability, with general practitioners (GPs), occupational therapists (OTs), and physiotherapists (PTs) working in Quebec (Canada), and identify areas of convergence and divergence between health professions. SUMMARY OF BACKGROUND DATA: Studies have demonstrated inadequacies of practices of clinicians with regard to LBP management and prevention of persistent disability. Barriers to use of evidence by clinicians should be evaluated to understand these inadequacies and develop implementation strategies. METHODS: Sixteen PTs, 8 OTs, and 8 GPs were recruited with different levels of experience and practice location (urban or rural). They were asked to follow management recommendations (Clinic on Low-back Pain in Interdisciplinary Practice [CLIP] guidelines), with a minimum of 2 patients. Individual semistructured interviews were used to identify barriers to use of management recommendations aimed at preventing LBP disability. Barriers between health professions were compared. RESULTS: Barriers to use were lesser for OTs and greater for GPs, with divergences among PTs. OTs agreed with the guidelines, found them compatible with their current practice, and thought that using them would prevent persistent disability. GPs and PTs thought that the guidelines did not provide enough information on the pathophysiological management of LBP. GPs thought that it would be difficult to implement the guidelines in everyday practice. All 3 groups thought that management recommendations could conflict with patient expectations. CONCLUSION: To address identified barriers, a process of care is proposed by fitting tasks to the most compatible providers. The task of GPs could focus on pain management through medication, red flag screening, encouragement to stay active, and reassurance. The tasks of PTs could center on pain management, general exercise, and encouragement to stay active. The tasks of OTs could focus on disability prognosis, yellow flags management, and return to activity parameters. The efficacy of this process of care to prevent persistent LBP disability should be assessed in a trial. PMID- 22310095 TI - Repeat surgical interventions following "definitive" instrumentation and fusion for idiopathic scoliosis: five-year update on a previously published cohort. AB - STUDY DESIGN: A retrospective case series. OBJECTIVE: To identify the overall reoperation rate and factors contributing to reoperation in a recent 5-year cohort of patients (2003-2007) undergoing spinal deformity surgery. These patients were compared with a previously published 15-year cohort of consecutive patients (1988-2002) from the same institution to assess for any significant differences in reoperation rates. SUMMARY OF BACKGROUND DATA: In a previously published report from this institution, the reoperation rate for patients with idiopathic scoliosis treated during a 15-year period (1988-2002) was 12.9%. That group was predominantly treated with first-generation TSRH (Medtronic, Memphis, TN) implants and CD implants. Lower profile, more rigid implant systems are now used along with refined techniques for correction of scoliosis deformity. We hypothesized that these factors would lead to lower rates of reoperation. METHODS.: The medical records of 452 consecutive patients (older than 9 yr) surgically treated for idiopathic scoliosis at one institution during 5 years (2003-2007) were reviewed to identify those who required reoperation. RESULTS: The reoperation rate for this cohort was 7.5% (34 of 452 patients). Compared with the prior cohort, significant decreases were noted with regard to total reoperation rate as well as reoperation due to infection and pseudarthrosis. Trends were noted toward decreased rates of reoperation due to prominent implants, dislodged implants, and implant proximity to vital structures. Within the newer cohort, a trend toward decreased reoperation rate was also noted for lower profile implant systems compared with first-generation TSRH implants. CONCLUSION: With the evolution of newer lower profile segmental implant systems that provide more rigid fixation and with the advancements in techniques for deformity correction, the repeat surgical intervention rate for idiopathic scoliosis has decreased. PMID- 22310096 TI - Biomechanical analysis of 4 types of pedicle screws for scoliotic spine instrumentation. AB - STUDY DESIGN: Numerical modeling and simulations of scoliotic spine instrumentation using monoaxial, uniaxial, polyaxial, and multiple-degrees-of freedom (6DOF) postloading pedicle screws. OBJECTIVE: To biomechanically analyze the general curve reduction effects and bone-screw force levels of monoaxial, uniaxial, polyaxial, and 6DOF pedicle screws for scoliotic spine instrumentation. SUMMARY OF BACKGROUND DATA: The ideal spinal fusion construct for treating scoliosis is still debatable. Studies on the effects of different types of implants were mainly based on postoperative radiograph measurements. Systematic studies are yet to be done on how bone-screw forces are correlated with screw types. METHODS: Computer biomechanical models were built using 3-dimensional geometry and spine stiffness of 10 patients with adolescent idiopathic scoliosis having undergone spinal instrumentation. The surgical instrumentations were simulated each time, using a different type of screw. For each case and screw type, 15 screw placement variations were simulated to investigate their effects on bone-screw forces. RESULTS: The maximum differences between different screw types were 6.4 degrees , 1.1 degrees , and 4.7 degrees , respectively, for main thoracic Cobb angles, main thoracic apical vertebral rotation, and thoracic kyphosis (1.2 degrees , 0.3 degrees , and 0.3 degrees on average). The average bone-screw forces were higher for monoaxial (229 N +/- 140 N) than uniaxial (206 N +/- 122 N), polyaxial (141 N +/- 99 N), and 6DOF screws (103 N +/- 42 N). Bone screw forces with monoaxial screws were, respectively, 1.1, 2.5, and 25 times more sensitive to screw placement variation than uniaxial, polyaxial, and 6DOF screws. CONCLUSION: The bone-screw loads of different screws were significantly different. The descending order of bone-screw loads was monoaxial, uniaxial, polyaxial, and 6DOF screws. For patients with large and stiff spinal deformities or for patients with compromised bone quality, screws with more degrees of freedom offer better perspective to reduce bone-screw connection failure. PMID- 22310097 TI - Accuracy of robot-assisted placement of lumbar and sacral pedicle screws: a prospective randomized comparison to conventional freehand screw implantation. AB - STUDY DESIGN: Single-center prospective randomized controlled study. OBJECTIVE: To evaluate the accuracy of robot-assisted (RO) implantation of lumbar/sacral pedicle screws in comparison with the freehand (FH) conventional technique. SUMMARY OF BACKGROUND DATA: SpineAssist is a miniature robot for the implantation of thoracic, lumbar, and sacral pedicle screws. The system, studied in cadaver and cohort studies, revealed a high accuracy, so far. A direct comparison of the robot assistance with the FH technique is missing. METHODS: Patients requiring mono- or bisegmental lumbar or lumbosacral stabilization were randomized in a 1:1 ratio to FH or RO pedicle screw implantation. Instrumentation was performed using fluoroscopic guidance (FH) or robot assistance. The primary end point screw position was assessed by a postoperative computed tomography, and screw position was classified (A: no cortical violation; B: cortical breach <2 mm; C: >=2 mm to <4 mm; D: >=4 mm to <6 mm; E: >=6 mm). Secondary end points as radiation exposure, duration of surgery/planning, and hospital stay were assessed. RESULTS: A total of 298 pedicle screws were implanted in 60 patients (FH, 152; RO, 146). Ninety-three percent had good positions (A or B) in FH, and 85% in RO. Preparation time in the operating room (OR), overall OR time, and intraoperative radiation time were not different for both groups. Surgical time for screw placement was significantly shorter for FH (84 minutes) than for RO (95 minutes). Ten RO screws required an intraoperative conversion to the FH. One FH screw needed a secondary revision. CONCLUSION: In this study, the accuracy of the conventional FH technique was superior to the RO technique. Most malpositioned screws of the RO group showed a lateral deviation. Attachment of the robot to the spine seems a vulnerable aspect potentially leading to screw malposition as well as slipping of the implantation cannula at the screw entrance point. PMID- 22310099 TI - Re: Niggemann P, Kuchta J, Beyer HK, et al. Spondylolysis and spondylolisthesis: prevalence of different forms of instability and clinical implications. Spine 2011;36:E1463-8. PMID- 22310098 TI - Sensory and autonomic innervation of the cervical intervertebral disc in rats: the pathomechanics of chronic discogenic neck pain. AB - STUDY DESIGN: An immunohistological analysis of the cervical intervertebral disc (IVD). OBJECTIVE: To investigate sensory and autonomic innervation of the rat cervical IVD. SUMMARY OF BACKGROUND DATA: Many clinicians are challenged with treating wide-ranging chronic neck pain. Several authors have reported that sympathetic nerves participate in chronic pain, and various sympathectomy procedures can effectively treat chronic pain. METHODS: The neuro-tracer Fluoro gold (FG) was applied to the anterior surfaces of C5-C6 IVDs from 10 Sprague Dawley rats to label the neurons of the innervating dorsal root ganglion (DRG), stellate ganglion (SG; sympathetic ganglion), and nodose ganglion (NG; parasympathetic ganglion). Seven days postsurgery, DRGs from level C1-C8, SG, and NG neurons were harvested, sectioned, and immunostained for calcitonin gene related peptide (CGRP; a marker for peptide-containing neurons) and isolectin B4 (IB4; a marker for nonpeptide-containing neurons). The proportion of FG-labeled DRG neurons that were CGRP-immunoreactive (CGRP-IR), IB4-binding, and non-CGRP-IR and IB4-binding, and the proportion of FG-labeled SG neurons and NG neurons were calculated. RESULTS: FG-labeled neurons innervating the C5-C6 IVD were distributed throughout the C2-C8 DRGs. The proportions of FG-labeled DRG neurons that were CGRP-IR, IB4-binding, non-CGRP-IR and IB4-binding, as well as SG neurons, and NG neurons were 20.6%, 3.3%, 55.7%, 8.9%, and 11.5%, respectively. The proportion of CGRP-IR FG-labeled DRG neurons was significantly higher than the proportion of IB4-binding FG-labeled DRG neurons at each level (P < 0.05). CONCLUSION: The C5-C6 IVD was innervated multisegmentally from neurons of the C2 C8 DRG, SG, and NG. Overall, 79.6% of the nerve fibers innervating the IVD were sensory nerves and 20.4% were autonomic nerves. Furthermore, 23.9% of the nerve fibers innervating the IVD were afferent sensory pain-related nerves, 8.9% were efferent sympathetic nerves, and 11.5% were efferent parasympathetic nerves. These findings may explain the wide-ranging and chronic discogenic pain that occurs via the somatosensory and autonomic nervous system. PMID- 22310100 TI - Synthesis, characterization, and cytotoxicity in vitro of the complex [Mn (Hptc) (phen) (OH)] n. AB - AIMS: A bridging ligand 2,4,6-pyridine tricarboxylic acid (H(3)ptc) and its manganese(II) complex [Mn(Hptc)(phen)(OH)]n(Hptc=2,4,6-pyridine tricarboxylic acid, phen=1,10-phenanthroline) have been synthesized and characterized. MAIN METHODS: The interaction with DNA (HeLa and KB) was carried out by fluorescence spectrum and gel electrophoresis assay. In vitro apoptosis assay and cytotoxicity assay detect the manganese (II) complex interaction with cancer cells. KEY FINDINGS: Fluorescence spectrum demonstrated the ability of the complexes to interact with DNA in an intercalative mode. Gel electrophoresis assay exhibited more effective DNA-cleavage activity. In vitro apoptosis assay of the complexes were examined on HeLa and KB cells, exhibited cytotoxic specificity and a significant cancer cell inhibitory rate. SIGNIFICANCE: The complex may be a latent antitumor agent as a result of its unique interaction mode with DNA and cancer cells inhibition effect. PMID- 22310101 TI - Surveillance study of healthcare-associated infections in a pediatric neurosurgery unit in Italy. AB - BACKGROUND: This prospective surveillance study was designed to estimate the incidence of healthcare-associated infections (HAIs) and to analyze the risk factors for their development in a pediatric neurosurgical unit. METHODS: The study was performed in an Italian teaching hospital from October 2008 through March 2010. All children (0-18 years) undergoing neurosurgery were included and monitored daily for the development of HAIs. RESULTS: The study included 260 patients, with a mean age of 4.3 +/- 4.7 years. Thirty-six HAIs were detected in 25 patients; catheter-related infections were the most frequent. Etiological identification was available in 22 cases; Gram-negative bacteria were the most commonly isolated pathogens. The incidence density was 11.0/1,000 patient days, and the incidence rate was 13.8/100 patients. The crude mortality was 0%. The risk of developing HAIs was related to the length of hospital stay, while the higher the age of the patients, the lower the risk of developing HAIs. CONCLUSION: To our knowledge, this survey is the first study to evaluate the overall incidence of HAIs and to explore the risk factors implicated in their development in neurosurgical pediatric patients. The most effective strategies to prevent these infections are reduction of the length of the hospital stay and improvement in device management. PMID- 22310102 TI - Worry and perceived threat of proximal and distal undesirable outcomes. AB - Individuals who are prone to worry tend to overestimate the likelihoods and costs of future undesirable outcomes. However, it is unclear whether these relations vary as a function of the timeframe of the event in question. In the present study, 342 undergraduate students completed a self-report measure of worry and rated the perceived probabilities and costs of 40 undesirable outcomes. Specifically, each participant estimated the probability that each of these outcomes would occur within three different timeframes: the next month, the next year, and the next 10 years. We found that the strength of the association between worry and probability estimates was strongest for the most proximal timeframe. Probability estimates were more strongly associated with worry for participants with elevated cost estimates, and this interactive effect was strongest for the most distal timeframe. Implications of these findings for understanding the etiology and treatment of excessive worry are discussed. PMID- 22310103 TI - The CD47-SIRPalpha pathway in cancer immune evasion and potential therapeutic implications. AB - Multiple lines of investigation have demonstrated that the immune system plays an important role in preventing tumor initiation and controlling tumor growth. Accordingly, many cancers have evolved diverse mechanisms to evade such monitoring. While multiple immune cell types mediate tumor surveillance, recent evidence demonstrates that macrophages, and other phagocytic cells, play a key role in regulating tumor growth through phagocytic clearance. In this review we highlight the role of tumor immune evasion through the inhibition of phagocytosis, specifically through the CD47-signal-regulatory protein-alpha pathway, and discuss how targeting this pathway might lead to more effective cancer immunotherapies. PMID- 22310104 TI - Cognitive maps in imagery neglect. AB - Patients with imagery neglect (RI+) show peculiar difficulties in orienting themselves in the environment. Navigational impairments could be due to a deficit in creating or using a mental representation of the environment (Guariglia, Piccardi, Iaria, Nico, & Pizzamiglio, 2005) or, according to the BBB model (Burgess, Becker, King, & O'Keefe, 2001), to a specific deficit in a mechanism that transforms an allocentric representation into an egocentric one and vice versa. Previous studies, however, do not allow discerning between a deficit in forming or in using a cognitive map, taking no notice of the fact that these are two different abilities underlain by different neuroanatomical areas, which could be independently impaired. Furthermore, the BBB model has never been verified in a population of brain-damaged patients. Therefore, we administered two tasks that separately assess the ability to create and use a cognitive map of the environment to 28 right brain-damaged patients (4 patients with imagery neglect and 4 patients with perceptual neglect) and 11 healthy participants. RI+ patients showed no specific deficit in creating or using a cognitive map, but failed to transform an egocentric representation of the environment into an allocentric one and vice versa, as predicted by the BBB model. PMID- 22310105 TI - Endothelial aging and gender. AB - The endothelium plays a pivotal role in maintaining vascular homeostasis, mainly by the production of the relaxing factor nitric oxide, which protects the vessel wall from the development of atherosclerosis. Aging is a powerful cardiovascular risk factor, associated with endothelial dysfunction both in normotensive subjects and in hypertensive patients. Premenopausal normotensive women are protected against the deleterious effect of aging on endothelial function, and age-related impairment of endothelial function is attenuated in premenopausal hypertensive women. This protective effect on endothelium seems to be mediated by endogenous estrogen, which preserves nitric oxide availability by activating the l-arginine-NO pathway in normotensive women and by inhibiting reactive oxygen species generation. Whether endogenous androgen may modulate endothelial function and the mechanisms involved are still unsolved issues, since data concerning the effect of testosterone on endothelium are scanty and contradictory. PMID- 22310106 TI - Testosterone pellet implants and migraine headaches: a pilot study. AB - The purpose of this prospective pilot study was to determine the therapeutic effect of continuous testosterone, delivered as a subcutaneous implant, on the severity of migraine headaches in pre- and post-menopausal patients. Twenty-seven women with a history of documented migraine headache were asked to rate their headache severity using a five-point scale at baseline (prior to therapy); and again, 3 months following treatment with testosterone implants. Improvement in headache severity was noted by 92% of patients and the mean level of improvement was statistically significant (3.3 on a 5 point scale). In addition, there was no difference in the level of improvement between pre- and post-menopausal cohorts. Seventy-four percent of patients reported a headache severity score of '0' (none) on testosterone implant therapy for the 3-month treatment period. Continuous testosterone was effective therapy in reducing the severity of migraine headaches in both pre- and post-menopausal women. PMID- 22310107 TI - Gene variants in PPARD and PPARGC1A are associated with timing of natural menopause in the general Japanese population. AB - OBJECTIVES: Timing of menopause affects postmenopausal health risks. The objective of this study was to evaluate the associations of the single nucleotide polymorphisms (SNPs) in peroxisome proliferator-activated receptor (PPAR)-related genes (PPARD, PPARG, and PPARGC1A) and environmental factors with timing of natural menopause among the general Japanese population. STUDY DESIGN: We analyzed cross-sectional data from 1758 women aged 40-69 years who were enrolled in the baseline surveys of the Japan Multi-institutional Collaborative Cohort (J MICC) Study. MAIN OUTCOME MEASURES: Associations of timing of natural menopause with its probable covariates and with target gene variants were evaluated by univariate and multivariate Cox proportional hazards models. RESULTS: Lower body mass index and later age at menarche were significantly associated with earlier natural menopause. Women with minor alleles at T-48444C in PPARD showed a significantly higher adjusted hazard ratio of 1.57 (95% confidence interval: 1.18 2.10) for earlier natural menopause. In contrast, women with minor alleles at Thr394Thr in PPARGC1A showed a significantly lower adjusted hazard ratio of 0.86 (0.76-0.97) for earlier natural menopause. These associations did not substantially alter when re-analyzed after excluding the subjects who self reported a history of diabetes or the subjects whose age was more than 65 years. CONCLUSIONS: Gene variants in PPARD and PPARGC1A might be associated with timing of natural menopause, probably through direct actions on the ovaries, among the general Japanese population. PMID- 22310108 TI - Benign paroxysmal positional vertigo of the posterior semicircular canal: efficacy of Santiago treatment protocol, long-term follow up and analysis of recurrence. AB - OBJECTIVES: To evaluate the efficacy of the Santiago treatment protocol for benign paroxysmal positional vertigo of the posterior semicircular canal, to analyse recurrence and to establish prognostic factors. MATERIAL AND METHODS: Four hundred and twelve patients with unilateral benign paroxysmal positional vertigo of the posterior semicircular canal were treated with the Semont manoeuvre and, if symptoms did not resolve, successive application of three Epley manoeuvres plus Brandt-Daroff exercises. RESULTS: Symptoms resolved in 404 patients (98.1 per cent); a single Semont manoeuvre was sufficient in 334 (81.2 per cent). Aetiology had no impact on resolution of symptoms or number of manoeuvres required. The estimated likelihood of recurrence was 14 per cent in the first year and 27 per cent after 10 years. The only factor indicating a worse prognosis was recurrence. CONCLUSION: In unilateral benign paroxysmal positional vertigo of the posterior semicircular canal, the above treatment protocol cured 98 per cent of patients. More than half of recurrences occurred in the first year. None of the analysed factors increased the likelihood of recurrence. PMID- 22310109 TI - Basil A. Pruitt, Jr., MD, FACS, FCCM: Editor-in-Chief , The Journal of Trauma, 1994-2011. PMID- 22310110 TI - American Association for the Surgery of Trauma and the Clinical Congress of Acute Care Surgery 2011 presidential address. PMID- 22310111 TI - Management of post-traumatic retained hemothorax: a prospective, observational, multicenter AAST study. AB - BACKGROUND: The natural history and optimal management of retained hemothorax (RH) after chest tube placement is unknown. The intent of our study was to determine practice patterns used and identify independent predictors of the need for thoracotomy. METHODS: An American Association for the Surgery of Trauma multicenter prospective observational trial was conducted, enrolling patients with placement of chest tube within 24 hours of trauma admission and RH on subsequent computed tomography of the chest. Demographics, interventions, and outcomes were analyzed. Logistic regression analysis was used to identify the independent predictors of successful intervention for each of the management choices chosen and complications. RESULTS: RH was identified in 328 patients from 20 centers. Video-assisted thoracoscopy (VATS) was the most commonly used initial procedure in 33.5%, but 26.5% required two and 5.4% required three procedures to clear RH or subsequent empyema. Thoracotomy was ultimately required in 20.4%. The strongest independent predictor of successful observation was estimated volume of RH <=300 cc (odds ratio [OR], 3.7 [2.0-7.0]; p < 0.001). Independent predictors of successful VATS as definitive treatment were absence of an associated diaphragm injury (OR, 4.7 [1.6-13.7]; p = 0.005), use of periprocedural antibiotics for thoracostomy placement (OR, 3.3 [1.2-9.0]; p = 0.023), and volume of RH <=900 cc (OR, 3.9 [1.4-13.2]; p = 0.03). No relationship between timing of VATS and success rate was identified. Independent predictors of the need for thoracotomy included diaphragm injury (OR, 4.9 [2.4-9.9]; p < 0.001), RH >900 cc (OR, 3.2 [1.4-7.5]; p = 0.007), and failure to give periprocedural antibiotics for initial chest tube placement (OR 2.3 [1.2-4.6]; p = 0.015). The overall empyema and pneumonia rates for RH patients were 26.8% and 19.5%, respectively. CONCLUSION: RH in trauma is associated with high rates of empyema and pneumonia. VATS can be performed with high success rates, although optimal timing is unknown. Approximately, 25% of patients require at least two procedures to effectively clear RH or subsequent pleural space infections and 20.4% require thoracotomy. PMID- 22310112 TI - Laparoscopic management of acute small bowel obstruction: evaluating the need for resection. AB - BACKGROUND: Acute small bowel obstruction (SBO) is a common condition encountered by the on-call emergency surgeon. The role of laparoscopy in the management of SBO continues to be defined. This modality can be limited by dilated bowel and inadequate assessment of compromised tissue. This review was undertaken to determine the reliability of laparoscopic evaluation and the subsequent need for bowel resection. METHODS: A retrospective review of all patients surgically managed for acute SBO between July 2005 and September 2010 was conducted. The clinical presentation, computed tomographic findings, indications for surgery, type of intervention, need for reoperation, length of stay (LOS), and outcomes were all abstracted. RESULTS: A total of 119 patients were surgically managed for acute SBO during this period, 63 with initial laparoscopy and 56 with an open procedure. Twenty-five (40%) of the laparoscopy patients were converted to open, leaving 38 completed laparoscopically. Of the completed group, three patients underwent bowel resection compared with 16 in the converted group (8% vs. 64%, p < 0.0001). No patients in the completed group required a subsequent procedure for bowel resection. Twenty-three (41%) patients in the open cohort required a resection. LOS was significantly reduced in the completed group (7.7 days) compared with the converted (11.0 days, p = 0.01) and open groups (11.4 days, p = 0.002). CONCLUSIONS: Overall, 32% of acute SBOs were managed solely with laparoscopy. No patients requiring a bowel resection were missed using this method of evaluation. Laparoscopic management should be considered as safe and effective initial therapy in most cases of acute SBO. PMID- 22310113 TI - Electroporation-mediated in vivo gene delivery of the Na+/K+-ATPase pump reduced lung injury in a mouse model of lung contusion. AB - BACKGROUND: Lung contusion (LC) is an independent risk factor for acute respiratory distress syndrome. The final common pathway in ARDS involves accumulation of fluid in the alveoli. In this study, we demonstrate the application of a potential gene therapy approach by delivering the Na+/K+-ATPase pump subunits in a murine model of LC. We hypothesized that restoring the activity of the pump will result in removal of excess alveolar fluid and additionally reduce inflammation. METHODS: Under anesthesia, C57/BL6 mice were struck along the right posterior axillary line 1 cm above the costal margin with a cortical contusion impactor. Immediately afterward, 100 MUg of plasmid DNA coding for the alpha,beta of the Na+/K+-ATPase pump were instilled into the lungs (LC-electroporation-pump group). Contusion only (LC-only) and a sham saline instillation group after contusion were used as controls (LC-electroporation sham). By using a BTX 830 electroporator, eight electrical pulses of 200 V/cm field strength were applied transthoracically. Mice were killed at 24 hours, 48 hours, and 72 hours after delivery. Bronchial alveolar lavage was recollected to measure albumin and cytokines by enzyme-linked immunosorbent assay. Pulmonary compliance was measured, and lungs were subject to histopathologic analysis. RESULTS: After the electroporation and delivery of genes coding for the alpha,beta subunits of the Na+/K+-ATPase pump, there was a significant mitigation of acute lung injury as evidenced by reduction in bronchial alveolar lavage levels of albumin, improved pressure volume curves, and reduced inflammation seen on histology. CONCLUSION: Electroporation-mediated gene transfer of the subunits of the Na+/K+-ATPase pump enhanced recovery from acute inflammatory lung injury after LC. PMID- 22310114 TI - Evolving role of endovascular techniques for traumatic vascular injury: a changing landscape? AB - BACKGROUND: Endovascular management of blunt aortic injury has dramatically reduced the morbidity and mortality associated with this specific injury. There remains a paucity of evidence quantifying the beneficial effects associated with endovascular (ENDO) techniques for other vascular injury types and little information regarding the impact ENDO techniques have had on the management of traumatic vascular injuries over time. METHODS: We performed a retrospective analysis of data from the National Trauma Data Bank over 2002 to 2006 and 2008 time periods (NTDB 7.2 and RDS 2008). Injured patients undergoing any arterial vascular repair procedure using ENDO or standard open techniques were determined using ICD-9-CM procedure codes. Abbreviated Injury codes were used to select patients who suffered subclavian, carotid, or thoracic aortic injury. Logistic regression was used to determine whether EARLY ENDO procedures (first 24 hours after injury) were independently associated with a lower risk of mortality. RESULTS: The percentage of ENDO procedures significantly increased over time irrespective of mechanism of injury. When aortic (thoracic), subclavian, and carotid arterial injuries were analyzed, a significant decrease in mortality over time was found. The percentage of ENDO procedures for all arterial injury subtypes significantly increased in the RECENT (2008) period. Seventy-five percentage of ENDO procedures occurred early (initial 24 hours) with 20% of those patients being hypotensive upon arrival (systolic blood pressure <90 mm Hg). For patients who had vascular procedures in the RECENT period, regression analysis revealed that early ENDO procedures were independently associated with a 35% reduction in mortality risk (odds ratio, 0.65; 95% confidence interval, 0.5-0.8) after controlling for major confounders including mechanism of injury and presence of hypotension on arrival. CONCLUSION: ENDO procedures for arterial injury have increased over time while mortality for arterial injury subtypes has significantly decreased. Early ENDO procedures are common and are independently associated with a lower risk of mortality. These results suggest outcomes after vascular injury may benefit from ENDO expertise and that ENDO techniques should be incorporated into the early treatment algorithm of trauma patients with vascular injury, particularly those that require difficult operative exposure. PMID- 22310115 TI - Emergency uncrossmatched transfusion effect on blood type alloantibodies. AB - BACKGROUND: Trauma patients receive emergency transfusions of unmatched Type O Rh negative (Rh-) blood until matched blood is available. We hypothesized that patients given uncrossmatched blood may develop alloantibodies, placing them at risk for hemolytic transfusion reactions (HTRs). METHODS: Data regarding alloantibody profiles and HTR occurrence were collected from the records of trauma patients at our university-based trauma center who received emergency uncrossmatched blood from July 2008 to August 2010. RESULTS: A total of 132 patients received 1,570 units of packed red blood cells. Mean injury severity score was 28 +/- 1.3. Forty-five (34%) patients died: 27 on hospital day 1; the remaining 18 had no evidence of HTR before death. Four Rh- female patients received Rh+ fresh frozen plasma, but none received Rh+ packed red blood cells. Three Rh- male patients received both Rh+ packed red blood cells and fresh frozen plasma, and one received Rh+ fresh frozen plasma. One patient developed anti-Rh D antibodies. None experienced HTR. One female patient had HTR from reactivation of anamnestic JK antibodies. Thirteen (33%) of 39 patients met criteria for HTR based on urinalysis and 29 (40%) of 72 patients tested met criteria for HTR based on hemoglobin and bilirubin values. Only one patient had confirmed HTR. CONCLUSION: High rates of injury recidivism in trauma patients increase the likelihood of multiple blood transfusions during their lifetime. Rh- patients who receive Rh+ blood are at risk of developing anti-Rh antibodies, putting them at risk for HTR. The conservation of Rh- blood for use in female patients may be detrimental to Rh- male patients. Laboratory diagnostic criteria for HTR are nonspecific in the trauma population and should be used with caution. PMID- 22310116 TI - Initial hematocrit in trauma: a paradigm shift? AB - BACKGROUND: After severe trauma and hemorrhage, it is generally assumed that the rate of fluid shift from the interstitial space into the vasculature is relatively slow and that initial hematocrit (Hct) does not reflect estimated blood loss. This study challenges that idea and tests the hypothesis that initial Hct correlates with signs of shock and hemorrhage in trauma patients. METHODS: Data were retrospectively reviewed from 198 trauma patients requiring emergency surgery at a Level I center from July 2009 to April 2010. Patients were divided into quartiles based on the initial Hct measured within 10 minutes of arrival. Categorical data were compared using chi(2) test or Fisher's exact test, as appropriate. Normally distributed data were compared using Student's t test or analysis of variance. Nonparametric data were compared with a Mann-Whitney U test or Kruskal-Wallis test. Post hoc analysis was conducted using the Bonferroni correction or paired Mann-Whitney U tests. RESULTS: The study population was 83% male, aged 35 +/- 1 years (mean +/- SE), with 71% penetrating injuries. Lower initial Hct correlated with hypotension (p < 0.001), acidosis (p = 0.003), altered mental status (p < 0.001), Injury Severity Score (p < 0.001), Revised Trauma Score (p < 0.001), estimated blood loss (p < 0.001), and usage of packed red blood cells (p < 0.001), fresh frozen plasma (p = 0.003), crystalloid (p = 0.021), and vasopressors (p < 0.001). CONCLUSION: Admission Hct correlates with signs of shock and hemorrhage in trauma patients requiring emergency surgery because fluid shifts rapidly from the interstitial space into the vasculature. This finding of a rapid Hct change contradicts the current teaching in most trauma textbooks. PMID- 22310117 TI - Is contrast exposure safe among the highest risk trauma patients? AB - BACKGROUND: Despite improvements in the diagnosis and management of acute kidney injury (AKI), posttraumatic renal dysfunction continues to be associated with increased morbidity and mortality. Intravenous (IV) contrast is known to induce AKI in high-risk groups including the elderly and critically ill. We sought to determine whether IV contrast exposure among high-risk trauma patients resulted in renal dysfunction as defined by the Acute Kidney Injury Network criteria. METHODS: We performed a 3-year retrospective analysis of all patients admitted to our Level I trauma center surgical intensive care unit for >48 hours. Patients with preexisting chronic renal dysfunction were excluded. We performed univariate and bivariate analyses to identify risk factors for AKI. Multivariable logistic regression analysis identified independent predictors for AKI. Subgroup analysis was undertaken among high-risk groups to include elderly patients (aged >=65 years) with admission hypotension (systolic blood pressure <90 mm Hg) and an Injury Severity Score (ISS) >=25. RESULTS: Of the 6,317 patients, 571 (9.0%) patients met the inclusion criteria; 170 (29.8%) patients developed AKI. Age >=65 years (odds ratio [OR] 2.26, 95% confidence interval [CI] = 1.06-4.80, p <0.034) and ISS >=25 (OR 1.86, 95% CI = 1.12-3.07, p <0.015) were determined to be independent predictors of AKI. IV contrast was not identified to be a predictor of AKI. Upon subgroup analysis, IV contrast exposure was not a predictor of AKI among the elderly, hypotensive, or severely injured patients (ISS >=25). CONCLUSION: A complete trauma workup including studies requiring IV contrast exposure should be considered safe even among high-risk trauma patients. PMID- 22310118 TI - Contemporary management of renal trauma: differences between urologists and trauma surgeons. AB - BACKGROUND: The purpose of this study was to evaluate the contemporary practice patterns of urologists (UR) and trauma surgeons (TS) regarding controversial topics in the management of renal trauma (RT). METHODS: We conducted a national survey of all Society of Genitourinary Reconstructive Surgeons members and a random sampling of American Association for the Surgery of Trauma members between October and November 2010 via email, regarding management routines for various stages of blunt and penetrating RT. RESULTS: Response rate was 33%. In all, 21% of TS and 3% of UR (p = 0.005) do not use any tests to confirm the presence of another kidney before exploring an expanding retroperitoneal hematoma, despite lack of preoperative imaging. To confirm the presence of another kidney, UR prefer the "one-shot" intravenous pyelogram (82%), whereas TS prefer palpation (61%; p < 0.001). TS do not obtain primary renal vascular control before opening the retroperitoneal, whereas UR do (21% vs. 71%; p < 0.001). TS utilize early angiography for the control of intravascular contrast extravasation more commonly than UR (88% vs. 55%; p < 0.001). TS overutilize ureteral stenting (50% vs. 24%; p < 0.001) for isolated collecting system injuries compared with UR. Differences in practice patterns between TS and UR tend to follow differences in published guidelines. CONCLUSION: There is an apparent lack of communication and differing treatment methods for RT. That there are two camps with differing "community standards of practice" indicates that there is a desperate need for reeducation and for large-scale, multi-institutional prospective studies on RT to "standardize" management. PMID- 22310119 TI - Play or pay: a financial model for trauma care in a regional trauma system. AB - BACKGROUND: Trauma systems are threatened from declining reimbursement. To increase trauma system participation in Mississippi, a novel "Play or Pay" (PoP) state trauma funding law went into effect on September 1, 2008. Hospitals were required to participate in the trauma system or pay a fee of up to $1.5 million per year. Funds generated are distributed for uncompensated care to hospitals participating in the trauma system. The purpose of this study was to evaluate the effect of PoP on a bordering state's Level I trauma center. METHODS: Patients living in the PoP state at the time of injury who were admitted to a regional Level I trauma center from 2006 to 2009 were eligible. Demographics, payer source, and injury severity were determined. The reimbursement ratio (reimbursement or charges) (REIMBR) was calculated for each patient. Patients admitted before PoP (PRE) were compared with those admitted after (POST). RESULTS: Trauma system participation increased in the PoP state PRE (70 of 107 [65%]) versus POST (85 of 106 [80%], p < 0.05). Transfers of Mississippi residents from referring hospitals to the regional Level I trauma center increased PRE (30.0%) versus POST (36.8%, p < 0.05). Payer mix was significantly different PRE versus POST with an increase in self-pay (37.4% POST vs. 36.5% PRE, p < 0.05) and a decrease in commercial insurance (36.0% POST vs. 41.0% PRE, p < 0.05). The REIMBR significantly decreased PRE (1.11 +/- 1.43) compared with POST (0.91 +/- 1.07, p < 0.05). At the same time, there was an increase in funds received from the PoP state. After accounting for increased funds, there was a significant increase in the adjusted REIMBR PRE (1.21 +/- 1.53) versus POST (1.49 +/- 4.51, p < 0.05). CONCLUSIONS: A PoP policy in a neighboring state was associated with more transfers, a change in payer mix, and a decrease in the REIMBR. However, funds received from the PoP state ameliorated the negative financial impact on bordering state's Level I trauma center. The Mississippi legislature's foresighted PoP policy created a truly regional trauma system, blind to state lines. PMID- 22310120 TI - Western Trauma Association critical decisions in trauma: management of the mangled extremity. AB - BACKGROUND: The operative management of mangled extremities after trauma remains controversial. We have sought to develop an evidence-based algorithm to help guide practitioners when faced with these relatively infrequent but very challenging clinical dilemmas. METHODS: The Western Trauma Association Critical Decisions Committee queried the literature to identify high-quality managements that would help guide the care of mangled extremities. When good data were not available, the Committee relied on expert opinions, either from the literature or from our senior members. RESULTS: Virtually, all the scoring systems used to guide therapy have not been proven to be valid. Hemodynamically unstable patients who failed to respond to initial resuscitation should be taken to the operating room for exploration and vascular control. Those who are stable should undergo a stepwise vascular and neurologic evaluation process. A comprehensive evaluation of factors that may help predict the appropriateness of limb salvage should be done in the operating room. Patients who are not candidates for salvage should undergo primary amputation. Those who are should undergo attempts at limb salvage. CONCLUSIONS: Patients with mangled extremities remain a significant management challenge. This algorithm represents a guideline based on the best evidence available in the literature and expert opinion. It does not establish a standard of care. It should provide a framework for treating physicians and other healthcare professionals to guide therapy, considering individual patients' clinical status and institutional resources. PMID- 22310121 TI - Future of acute care surgery: a perspective from the next generation. AB - BACKGROUND: Access to emergent surgical care has been identified as a crisis in the United States. To address this challenge, the American Association for Surgery of Trauma has developed a fellowship in acute care surgery (ACS) to reestablish broad-based surgical capabilities. But the viability of this new discipline will rest on the interests of the next generation of surgeons. The objective of this study was to determine key factors influencing the choice of surgical specialties among medical students with a focus on their interest in trauma/ACS (T/ACS). METHODS: An online questionnaire was distributed to students at four medical schools affiliated with Level I trauma centers, one of which also has an ACS fellowship. The survey was sent to medical students at all levels (first to fourth year). Students with an interest in surgery as a career were asked to complete the survey and rank factors and experiences influencing career selection on a scale of 1 (no influence) to 10 (critical). Students were also asked to select their top five surgical specialties. RESULTS: Three hundred thirty-seven students interested in surgery responded. Mean age was 26 years +/- 0.2 years (range, 20-37 years), 58% were men, and 86% were single. Respondents were distributed evenly over medical schools and medical school years. The three most popular career choices were orthopedics (16%), T/ACS (12%), and pediatric surgery (8%). As students progressed through medical school, lifestyle factors such as predictable hours and family time became more important in influencing their career choice. Overall, 115 students (34%) selected emergent surgery (T/ACS) as one of their top three career choices. Factors that were ranked significantly higher by students interested in T/ACS were related to professional satisfaction. These students also placed less emphasis on lifestyle factors when choosing a surgical career. CONCLUSIONS: Our results indicate that there is a reassuring interest to address the growing demand for emergency surgery among current medical students exposed to a broad range of T/ACS patients in Level I trauma centers. The T/ACS model is in accordance with the drives of these students looking for a diverse and challenging profession. Academic societies should make further efforts to encourage medical students to pursue T/ACS. PMID- 22310122 TI - Impact of a defined management algorithm on outcome after traumatic pancreatic injury. AB - BACKGROUND: The optimal management of pancreatic injuries, specifically with respect to defining ductal integrity, remains controversial. Our previous experience suggested that decisions based on probability of ductal injury might improve outcome. Consequently, a management algorithm (ALG) was developed and implemented. The purpose of this study was to evaluate the impact of this ALG on outcomes. METHODS: Consecutive patients more than 13 years with pancreatic injuries subsequent to the development of the ALG were evaluated. Pancreatic injuries were defined as proximal or distal and ductal injuries classified as definite, high, low, or indeterminate (IND) probability. Pancreas-related morbidity (fistula, abscess, and pseudocyst) and mortality were recorded. Patients managed by the ALG were compared with the previous study (PS). RESULTS: In all, 245 patients were identified; 35 died within 12 hours and were excluded. Demographics and severity of shock (24-hour transfusions) were similar between groups. Pancreas-related morbidity for proximal injuries was 13.8% in the ALG group and 13.5% in the PS (p = 0.948). Pancreas-related morbidity was significantly reduced in the ALG group for distal injuries requiring drainage alone (11% vs. 25%, p = 0.05) and for distal injuries requiring resection + drainage (26% vs. 58%, p = 0.003) when compared with the PS. There was no pancreas-related mortality in the ALG group (1.6% in the PS group, p = 0.065). CONCLUSIONS: Adherence to a defined ALG simplified the management of traumatic pancreatic injuries and contributed to a reduction in both pancreas-related morbidity and mortality. The majority of all proximal pancreatic injuries can be treated with drainage alone. For distal injuries, a clinical decision based on defined parameters and suspicion of ductal injury dictates definitive management. PMID- 22310123 TI - Changes in massive transfusion over time: an early shift in the right direction? AB - BACKGROUND: Increasing evidence suggests that high fresh frozen plasma:packed red blood cell (FFP:PRBC) and platelet:PRBC (PLT:PRBC) transfusion ratios may prevent or reduce the morbidity associated with early coagulopathy which complicates massive transfusion (MT). We sought to characterize changes in resuscitation which have occurred over time in a cohort severely injured patients requiring MT. METHODS: Data were obtained from a multicenter prospective cohort study evaluating outcomes in blunt injured adults with hemorrhagic shock. MT was defined as requiring >=10 units PRBCs within 24 hours postinjury. Mean PRBC, FFP, and PLT requirements (per unit; 6 hours, 12 hours, and 24 hours) were determined over time (2004-2009). Sub-MT, those patients just below the threshold for MT, were defined as requiring >=7 and <10 units PRBCs in the initial 24 hours. The percent of resuscitation given at 6 hours relative to 24 hours total (6 of 24%) was determined and compared across "early" (admission until December 2007) and "recent" (after December 2007) periods for each component. RESULTS: Over the study time period (2004-2009) for the MT group (n = 526), initial base deficit and presenting international normalized ratio were unchanged, while Injury Severity Score was significantly higher. The percent of patients who required MT overall significantly decreased over time. No significant differences were found over time for six-hour, 12-hour, or 24-hour FFP:PRBC and PLT:PRBC transfusion ratios in MT patients. Sub-MT patients (n = 344) had significantly higher six hour FFP:PRBC ratios and significantly higher six-hour,12-hour, and 24-hour PLT:PRBC ratios in the recent time period. The six h/24 h% total for FFP and PLT transfusion was significantly greater in the recent time period. (FFP: 54% vs.70%; p = 0.004 and PLT 46% vs. 61%; p = 0.048). CONCLUSION: In a severely injured cohort requiring MT, FFP:PRBC and PLT:PRBC ratios have not changed over time, whereas the rate of MT overall has significantly decreased. During the recent time period (after December 2007), significantly higher transfusion ratios and a greater percent of 6-hour/24-hour FFP and PLT were found in the sub-MT group, those patients just below the PRBC transfusion threshold definition of MT. These data suggest early, more aggressive attainment of high transfusions ratios may reduce the requirement for MT and may shift overall blood requirements below those which currently define MT. Further prospective evidence is required to verify these findings. PMID- 22310124 TI - Unique pattern of complications in elderly trauma patients at a Level I trauma center. AB - BACKGROUND: Trauma centers are caring for increased proportions of elderly patients. Although age and Injury Severity Score are independently associated with mortality, trauma centers were originally designed to care for seriously injured patients without age-specific guidelines. We hypothesized that elderly patients would have different complication patterns than their younger counterparts. METHODS: The trauma registry of an American College of Surgeons verified Level I trauma center was queried for all patients older than 14 years admitted between January 2005 and December 2008. Mechanism, mortality, and complications were evaluated after dividing patients into eight age groups. RESULTS: Of the 15,223 patients, 13% were elderly (>=65), and 86% were injured via a blunt mechanism. Increasing age correlated with fatality (all Injury Severity Scores), end-organ failure, and thromboembolic complications (deep venous thrombosis and coagulopathy). Analysis revealed a significant breakpoint at 45 years of age for mortality, decubitus ulcer, and renal failure (all p values <0.05). Infectious complications (sepsis, wound infection, and abscess) all peaked between 45 years and 65 years and then declined with increasing age. CONCLUSIONS: We document that elderly trauma patients suffer the same complications as their younger counterparts, albeit at a different rate. More importantly, we identified a "breakpoint" of increased risk of complications and mortality at greater than 45 years. Although the mechanisms behind these observations remain unknown, understanding their unique patterns may allow appropriate allocation of resources and focus research efforts on interventions that should improve outcomes. PMID- 22310125 TI - Geriatric trauma service: a one-year experience. AB - BACKGROUND: Trauma centers nationwide have been experiencing an increase in their elderly trauma patients because of an ever growing elderly population within the United States. Many studies have demonstrated the physiologic differences between an older trauma patient versus a younger trauma patient. Coupling these differences with their coexisting medical comorbidities, makes caring for this population extremely challenging. To meet these challenges, we organized a geriatric trauma unit specifically designed with a multidisciplinary approach to take a more aggressive stance to the care of the geriatric trauma patient. METHODS: We created a geriatric trauma unit at our Level II trauma facility, called the G-60 unit. This unit opened for admission in August 2009. Inclusion criteria included all trauma patients older than 60 years. Data were abstracted from our G-60 unit from the period of August 2009 to July 2010. We compared these data to a similar patient population (control group) from January 2008 to December 2008. RESULTS: Our Trauma Data Bank yielded 673 patients for the above queried time period. The G-60 group contained 393 patients, while the control group had 280 patients. A decrease was seen among the G-60 group in all categories: average emergency department length of stay (LOS), average emergency department to operating room time, average surgical intensive care unit LOS, and average hospital LOS. A 3.8% mortality rate was found in the G-60 group compared with a 5.7% mortality rate in the control group. Our analysis also showed rate of 0% pneumonia, 1.3% respiratory failure, and 1.5% urinary tract infection in the G 6O group, while the control group had a rate of 1.8% pneumonia, 6.8% respiratory failure, and 3.9% urinary tract infection. CONCLUSION: Our data from the 1-year experience of our G-60 unit show that addressing the specific needs of elderly trauma patients will lead to better outcomes. PMID- 22310126 TI - Specific inhibition of AQP1 water channels in human pulmonary microvascular endothelial cells by small interfering RNAs. AB - BACKGROUND: Aquaporin (AQP)-1 is expressed in most microvasculature endothelial cells forming water channels that play major roles in a variety of physiologic processes. Our aim was to investigate the regulatory functions of AQP1 on trancellular and paracellular permeability. METHODS: We designed, synthesized, and used small interfering RNAs (siRNAs) selective for AQP1 and investigated their effectiveness in altering AQP1-mediated permeability in human pulmonary microvascular endothelial cells. RESULTS: Twenty-four hours after transfection of ECs with siRNAs targeting two different regions of the AQP1 transcript, AQP1 protein was inhibited by 47.8% to 74.6%. siRNAs containing the same percent of base pairs as the AQP1-siRNAs but in random sequence (i.e., scrambled siRNAs) had no effect. Suppression of AQP1 expression in ECs resulted in decreases in epithelial Na+ channel (ENaC) and Na-K ATPase of ECs, and the suppression ENaC alpha, beta, gamma, and Na-K ATPase were 43.1% to 48.2%,70.0% to 76.0%, 52.6% to 55.0%, and 72.7% to 79.3%, respectively. The reduced AQP1expression also resulted in decreased cell-cell junction protein level of VE-cadherin, which was suppressed by 36.5% to 59.5% but had no effect on occludin protein. Tube formation assay and tranwell assay showed AQP1 siRNAs induced high permeability of human pulmonary microvascular endothelial cells. Rho-kinase (ROCK) I and ROCK II were increased by 46.0% to 50.0% and 59% to 81%, respectively, AQP1 siRNA treatment accelerated the formation of F-actin bundles, demonstrating the activation of Rho/ROCK signaling pathway, and decreased mitochondrial membrane potential after AQP1 siRNA treatment, showing an important event of apoptosis process. CONCLUSIONS: The data demonstrate that AQP1 is a critical participate in regulating endothelial permeability and barrier function and provide direct evidence of the contribution of AQP1 to blood vessel formation. PMID- 22310127 TI - Enoxaparin and fondaparinux attenuates endothelial damage in endotoxemic rats. AB - BACKGROUND: Prophylactic use of anticoagulants for septic patients in intensive care unit is a standard therapy for the prevention of venous thrombosis. Moreover, recent studies have demonstrated the anti-inflammatory effects of anticoagulants such as Factor Xa inhibitors and heparins. However, there have been no studies to examine the effects of fondaparinux and enoxaparin when applied in a sepsis model. Therefore, we examined the anti-inflammatory effects and bleeding events when these agents are applied in a lipopolysaccharide challenge model. METHODS: Wistar rats received lipopolysaccharides followed by a bolus infusion of fondaparinux, enoxaparin, or placebo. Microscopic observation of the mesenteric microcirculation for endothelial damage and measurement of bleeding area after vascular puncture was performed (n = 6 in each group). In another series, blood samples were taken, and blood cell counts, coagulation markers, and organ damage markers were measured (n = 6 in each). RESULTS: Both leukocyte adherence to vascular endothelium and endothelial damage were reduced in fondaparinux and enoxaparin groups. The bleeding area was markedly increased in the fondaparinux group. Coagulation markers were maintained better in the enoxaparin group. Levels of organ damage markers were significantly suppressed in both fondaparinux and enoxaparin groups (p < 0.01, compared with control, each). CONCLUSIONS: Fondaparinux and enoxaparin reduce organ dysfunction by decreasing endothelial damage. However, bleeding was more prominent in the fondaparinux group compared with the enoxaparin group at an equipotent dose for anti-Xa activity. Because the setting of this experiment is different from the clinical use, further study is required for the comparison of both pharmaceuticals. PMID- 22310128 TI - Electrical stimulation improves peripheral nerve regeneration in streptozotocin induced diabetic rats. AB - We discuss if percutaneous electrical stimulation (ES) at 1 mA and 2 Hz after peripheral nerve transection could enhance axonal regeneration and functional recovery in diabetic animals. METHODS: Four groups of adult rats (group A: normal rats; group B: normal rats with ES; group C: streptozotocin- induced diabetic rats; and group D: streptozotocin-induced diabetic rats with ES) were subjected to sciatic nerve section followed by repair using silicone rubber conduits across a 10-mm gap. Rats in groups B and D received ES for 15 minutes every other day for three weeks. The groups A and C received no ES. RESULTS: At four weeks after surgery in groups B and D, immunohistochemical staining showed that lamina I and II regions in the dorsal horn ipsilateral to the injury were significantly calcitonin gene-related peptide-immunolabeled, and a significantly higher number of macrophages were recruited in the distal sciatic nerve compared with group C. In groups A, B, and D, electrophysiological results showed higher levels of reinnervation with significantly shorter latencies and faster nerve conductive velocities, and the histologic evaluations showed relatively larger mean values of myelinated axon densities and endoneurial areas compared with group C. CONCLUSIONS: Thus, the ES may improve the recovery of a severe peripheral nerve injury in diabetic animals, which could be considered as a supplementary treatment in diabetic neurotrauma. PMID- 22310129 TI - Comparison of massive blood transfusion predictive models in the rural setting. AB - BACKGROUND: Hemorrhage is the leading cause of preventable death in trauma patients, of which 3% require massive transfusion (MT). MT predictive models such as the Assessment of Blood Consumption (ABC), Trauma-Associated Severe Hemorrhage (TASH), and McLaughlin scores have been developed, but only included patients requiring blood transfusion during their hospital stay, excluding a large percentage of trauma patients. Our purpose was to validate these MT predictive models in our rural Level I trauma center patient population, using all major trauma victims, regardless of blood product requirements. METHODS: Review of all Level I trauma patients admitted in 2008 to 2009 was performed. ABC, TASH, and McLaughlin scores were calculated using 80% probability for the need for MT. RESULTS: Three hundred seventy-three patients were admitted; 13% had a penetrating mechanism and 52% were scene transports. MT patients had higher Injury Severity Score (median, 43 vs. 13; p < 0.001) and lower Trauma-Injury Severity Score (0.310 vs. 0.983; p < 0.001). Mortality was higher in MT patients (18.4% vs. 5.4%; p < 0.009). Thirty-eight (10%) required MT; 34 were predicted by ABC, one by TASH, and six by McLaughlin. ABC (area under the receiver operating characteristic [AUROC] = 0.86) was predictive of MT, whereas TASH (AUROC = 0.51) and McLaughlin (AUROC = 0.56) were not. CONCLUSIONS: The ABC score correctly identified 89% of MT patients and was predictive of MT in major trauma patients at our rural Level I trauma center; the TASH and McLaughlin scores were not. The ABC score is simpler, faster, and more accurate. Based on this work, we strongly recommend adoption of the ABC score for MT prediction. PMID- 22310130 TI - Single-center experience on endovascular reconstruction of traumatic internal carotid artery dissections. AB - BACKGROUND: Traumatic internal carotid artery dissection (CAD) has a potentially grave outcome. Anticoagulant therapy may be ineffective or contraindicated; surgery impractical. We present our experience with endovascular stenting in CAD patients. METHODS: From 2004 to 2011, 23 patients with angiographically proven traumatic CAD underwent endovascular stent-assisted arterial reconstruction based on clinical and radiographic criteria: contraindication or failure of anticoagulation, evidence of impending ischemic stroke, or need for urgent intracranial revascularization. Dissections were graded based on degree of stenosis and extent of injury. RESULTS: Seventeen patients (73.9%) presented with stroke or transient ischemic attack. Carotid revascularization was achieved with one (11 patients, 48%) or multiple stents (12 patients, 52%); distal protection was used rarely (three patients, 13%). No complications were directly attributed to stenting. Mean dissection-related stenosis improved from 72% +/- 28.87% to 4% +/- 8.29%. At a mean clinical follow-up of 28.7 months +/- 31.9 months, 16 patients (69.6%) improved, six (26.1%) remained stable, and one (4.3%) had died secondary to multiple traumatic injuries. At long-term follow-up, no patient had a transient ischemic attack or stroke or presented evidence of de novo in-stent stenosis or stent thrombosis. There were no neurologic sequelae after partial or total discontinuation of antiplatelet therapy in seven patients undergoing trauma related surgeries. CONCLUSIONS: Selected cases of traumatic CAD can be safely managed by endovascular stent-assisted angioplasty. Procedural complications are infrequent; the need for postprocedure antiplatelet therapy is a concern. Early detection is essential to avoid stroke. Stenting restores the integrity of the vessel lumen immediately, efficiently prevents the occurrence or recurrence of ischemic events, and avoids the need of long-term anticoagulation. PMID- 22310131 TI - Blunt splenic trauma: splenectomy increases early infectious complications: a prospective multicenter study. AB - BACKGROUND: The purpose of this study was to evaluate the effect of the method of splenic injury management on early infectious complications. METHODS: Prospective observational, multicenter study which included all patients with blunt splenic injury surviving at least 72 hours. Epidemiologic and clinical data, grade of splenic injury, method of splenic management, and infectious complications during the initial hospitalization were collected according to a standardized collecting datasheet. Logistic regression analysis was used to identify independent risk factors for infectious complications. RESULTS: During a 22-month period, 269 eligible patients were enrolled in the study. Overall, 105 (39.0%) patients were observed; 48 (17.8%) underwent successful angioembolization, 19 (7.1%) underwent splenorrhaphy, and 97 (36.1%) underwent splenectomy. Multivariate analysis adjusting for age, hypotension on admission, Glasgow Coma Scale, Injury Severity Score, Abbreviated Injury Scale, laparotomy, grade of splenic injury, and associated solid and hollow viscus injuries, showed that splenectomy had a significantly higher incidence of infectious complications than splenic preservation (adjusted odds ratio [95% confidence interval], 9.62 [3.04-30.30]; p < 0.001). A regression model analysis identified splenectomy, hypotension on admission, associated hollow viscus injury, and high Injury Severity Score as independent risk factors for infectious complications. Forward logistic regression analysis, which included only the 176 patients with grades III to V splenic injuries, identified splenectomy as the most significant independent risk factors for infection (adjusted odds ratio [95% confidence interval], 16.67 [3.76 71.43]; p < 0.001). CONCLUSIONS: Splenectomy is an independent risk factor for early infectious complications. Splenic-preserving techniques should be considered more liberally. PMID- 22310132 TI - One hundred percent fascial approximation can be achieved in the postinjury open abdomen with a sequential closure protocol. AB - BACKGROUND: Multiple techniques have been introduced to obtain fascial closure for the open abdomen. Vacuum-assisted closure has reduced but not eliminated the use of either split-thickness skin grafts to cover the exposed bowel or mesh (prosthetic or biological) approximation of the fascia. We hypothesized that a sequential closure technique performed by a systematic protocol would achieve a higher rate of primary fascial closure than other described techniques. METHODS: Our technique of sequential fascial closure was initiated in 2005. Patients with a postinjury open abdomen undergoing the technique were compared with those patients who did not follow the protocol. In brief, vacuum-assisted closure white sponges cover the bowel; the fascia is placed under moderate tension over the white sponges with no. 1-polydioxanone sutures; the black sponge is placed on top of this with the standard occlusive dressing; patients undergo partial fascial closure and replacement of the sponge sandwich every 2 days until completely closed. Protocol violations were defined as not returning to the operating room every other day and absence of fascial retention sutures. Patients who died before return to the operating room in the first 48 hours were excluded. RESULTS: One hundred consecutive patients underwent damage control surgery during the five year study period and survived to second laparotomy; 49 patients attained fascial closure at the second laparotomy. Fifty-one patients required an open abdomen after the second laparotomy and comprise the study population. The majority were men (80%) with a mean age of 34.7 years +/- 2.0 years, mean injury severity score of 37.1 +/- 2.4, and mean abdominal trauma index of 26.4 +/- 2.1. Average initial base deficit was 15.7 +/- 0.6 and 24-hour red cell transfusions were 20.4 +/- 2.4 units. Of the 51 patients, 29 followed the protocol and 100% had fascial closure. Of the 22 patients who did not follow the protocol, 12 (55%) attained fascial closure. There were no significant differences in injury severity score, abdominal trauma index, base deficit, or red cell transfusions between the two groups. CONCLUSIONS: A methodical approach with sequential fascial closure achieves 100% fascial approximation in our experience. This technique reduces the morbidity of the open abdomen and the cost of either complex abdominal reconstruction or biological mesh insertion. PMID- 22310133 TI - Differences in management and mortality with a bronchoalveolar lavage-based diagnostic protocol for ventilator-associated pneumonia. AB - BACKGROUND: Directed antibiotic therapy based on accurate bacteriology is critical to ventilator-associated pneumonia (VAP) treatment. Bronchoalveolar lavage (BAL) has been reported to be more accurate than endotracheal sputum aspirate (ESA) in VAP diagnosis. Our objective was to determine the frequency with which BAL results differ from ESA cultures and the outcomes of VAP with a BAL-based VAP protocol. METHODS: Prospectively collected microbiologic data on all trauma patients with VAP from 2007 through 2009 were reviewed. Per protocol, a positive ESA prompts a BAL and initiation of broad empiric antibiotics with de escalation based on BAL results. Patients diagnosed with VAP by the protocol were compared with those diagnosed outside of the protocol using univariate and multivariate linear regression analysis. Concordance of ESA and BAL results was evaluated, and cause of death was determined. RESULTS: Of 137 patients with VAP, 96 were diagnosed by the protocol (protocol group) and had 102 pairs of cultures. Twenty-six patients (27%) with 28 pairs of cultures (27.4%) had discordant results. Of discordant pairs, 17 (61%) showed bacteria of a different Gram's stain. Methicillin-sensitive Staphylococcus aureus was the most common causative organism. Mortality was lower in the protocol group (6.3%) than the nonprotocol group (22%, p = 0.014) and mechanically ventilated patients without VAP (24%, p = 0.35) but with comparable Injury Severity Score (ISS). VAP-attributable mortality in the protocol group was 1%. CONCLUSIONS: Use of a BAL-based diagnostic protocol affects management of trauma patients with VAP by improving identification of causative microorganisms and is associated with low overall mortality and VAP attributable mortality. PMID- 22310134 TI - The Baux score is dead. Long live the Baux score: a 27-year retrospective cohort study of mortality at a regional burns service. AB - BACKGROUND: To assess trends in mortality after burn injuries treated in a regional specialist burns service between 1982 and 2008. METHODS: Patient and burn-specific information and mortality were collated from written admission ledgers and the hospital coding department for 11,109 patients. The data set was divided into age cohorts (0-14, 15-44, 45-64, and >65 years) and time cohorts (1982-1991, 1992-2000, and 2000-2008). Lethal area 50 (LA50) was calculated by logistic regression and probit analysis. Mortality was related to the Baux score (age + total % burned surface area) by logistic regression. RESULTS: In the time period 2000 to 2008, the LA50 values with approximate 95% confidence intervals (CIs) were 100% (CI, 85.5-100%) in the 0 to 14 cohort (LA10, 78.3%; CI, 64.1 92.5%), 76.4% (CI, 69.1-83.8%) in the 15 to 44 cohort, 58.6% (CI, 50.8-66.5%) in the 45 to 64 cohort, and 30.8% (CI, 24.7-36.9%) in the >65 cohort. The point of futility (the Baux Score at which predicted mortality is 100%) was 160 and the Baux50 (the Baux score at which predicted mortality is 50%) was 109.6 (CI, 105.9 113.4) in the 2000 to 2008 cohort. CONCLUSIONS: Mortality is markedly improved over earlier data from this study and other historical series and compares favorably with outcomes published from the US National Burn Repository. The Baux Score continues to provide an indication of the risk of mortality. Survival after major burn injury is increasingly common, and decisions by nonspecialist about initial triage, management, and futility of care should be made after consultation with a specialist burn service. PMID- 22310135 TI - Trimming- and pruning-related injuries in the United States, 1990 to 2007. AB - BACKGROUND: Trimming and pruning equipment is used frequently in the United States, and associated injuries are common. METHODS: The National Electronic Injury Surveillance System database was used to examine trimming- and pruning related injuries treated in US hospital emergency departments from 1990 through 2007. RESULTS: An estimated 648,100 individuals (95% confidence interval: 535,500 760,700) were treated in US hospital emergency departments for trimming- and pruning-related injuries during the 18-year study period. The average annual injury rate was 13.0 per 100,000 US population, and the annual rate of injury increased 35.1% from 11.4 in 1990 to 15.4 in 2007 (slope = 0.241, p < 0.01). Approximately two-thirds (67.6%) of the injuries occurred among males, and 62.8% of incidents occurred to individuals 18 years to 54 years of age. Lacerations and puncture injuries occurred most often (71.0%), and injuries to the arms and hands accounted for 67.8% of cases. A majority (56.8%) of injuries involved the use of a power tool. The most common project at the time of injury was hedge/shrub trimming (66.5%), followed by grass/lawn trimming (24.3%) and tree trimming (9.1%). Patients required hospitalization in 2.1% of cases. Most injury incidents (98.5%) occurred around the home. CONCLUSIONS: This is the first study to examine trimming- and pruning-related injuries in the United States using a nationally representative sample. The increasing number and rate of injuries associated with trimming activities in the United States underscore the need for increased prevention efforts, including enhanced safety features of trimming equipment and better education of equipment operators regarding the potential hazards of trimming activities. PMID- 22310136 TI - A cost-minimization analysis of phenytoin versus levetiracetam for early seizure pharmacoprophylaxis after traumatic brain injury. AB - BACKGROUND: Recent data indicate comparable efficacy and safety for levetiracetam (LEV) when compared with phenytoin (PHT) for prophylaxis of early seizures after traumatic brain injury. The purpose of this study was to conduct a cost minimization analysis, from the perspective of both the acute care institution (cost) and patient (charges), comparing these two strategies. METHODS: A decision tree was constructed to include baseline event probabilities obtained from detailed literature review, costs, and charges. Monte Carlo simulation was used to derive the mean costs and charges per patient treated with the LEV when compared with the PHT strategy. Adverse event probabilities, costs, charges, and frequency of laboratory determination for the PHT group were varied in sensitivity analyses. RESULTS: Literature review indicated equal efficacy of PHT versus LEV for early seizure prevention. The PHT strategy was superior to the LEV strategy from both the institutional (mean cost per patient $151.24 vs. $411.85, respectively) and patient (mean charge per patient $2,302.58 vs. $3,498.40, respectively) perspectives. Varying both baseline adverse event probabilities and frequency of laboratory testing did not alter the superiority of the PHT strategy. LEV replaced PHT as the dominant strategy only when the cost/charge of treating mental status deterioration was increased markedly above baseline. CONCLUSIONS: From both institutional and patient perspectives, PHT is less expensive than LEV for routine pharmacoprophylaxis of early seizures among traumatic brain injury patients. Pending compelling efficacy data, LEV should not replace PHT as a first-line agent for this indication. PMID- 22310137 TI - The use of acellular human dermis composite graft for upper eyelid reconstruction in ocular injury. AB - BACKGROUND: Repair of the upper lid is more difficult because of the unique anatomic requirements of the upper eyelid. The eyelid must remain pliable, allow for retraction and protraction, and also have a mucous membrane on the posterior surface. A number of procedures are available to repair large to total upper eyelid defects. These surgical techniques include lower lid switch flaps and lower lid bridge flaps. However, these procedures have several disadvantages, such as the partial or total sacrifice of the lower lid and the need for secondary correction. The authors present a new surgical technique using composite graft of acellular dermis and split-thickness buccal mucosa in the reconstruction of traumatic full-thickness upper eyelid defects to achieve satisfactory functional and esthetic results. METHOD: In this retrospective case series, eight patients requiring full-thickness upper eyelid reconstruction were evaluated. Defect size ranged from 20 mm to 28 mm horizontally and from 5 mm to 8 mm vertically. For eyelid reconstruction, the acellular dermis composite graft was sutured into the posterior lamella defect; the anterior lamella was repaired with a bipedicled orbicularis flap and a free skin graft. RESULTS: Acellular dermis composite grafts achieved complete resolution of lagophthalmos and follow up of 6 months to 31 months revealed a good outcome in all eight cases. No adverse situation of the grafts viability was encountered. Postoperative complications occurred in two patients; one had eyelid margin notching and the other had a mild ptosis. CONCLUSIONS: The acellular dermis composite graft is a good match for the posterior lamella of the eyelid in terms of texture and contour. The acellular dermis composite graft technique is useful for the reconstruction of large upper eyelid defects resulting from burns or trauma because this method results in complete repair of defects without causing notable deformity. PMID- 22310138 TI - Persistent high level of circulating midregional-proadrenomedullin and increased risk of nosocomial infections after septic shock. AB - BACKGROUND: Risk stratification could represent a major improvement in critically ill patients' management. The objective of this study is to evaluate the association between concentrations of four circulating prohormones (C-terminal provasopressin, midregional-proadrenomedullin (MR-proADM), midregional-proatrial natriuretic peptide, and C-terminal- proendothelin-1) and the occurrence of nosocomial infections (NIs) in septic shock patients. METHODS: We performed an observational, clinical study with septic shock patients (n = 98) recruited from adult intensive care units in a university hospital. Prohormone concentrations were assessed three times within the first week after the onset of septic shock using an immunoluminometric assay. RESULTS: Significantly elevated plasmatic MR proADM concentrations were measured in patients who went on to develop NIs in comparison with patients who remain infection free (p = 0.043). No differences were observed for the other three prohormone concentrations. CONCLUSIONS: Elevated plasmatic MR-proADM concentration is associated with the development of secondary NIs after septic shock. This information, if confirmed in a larger group of patients, could represent a major advance in the monitoring of intensive care unit patient infectious risk. PMID- 22310139 TI - Pulmonary edema in near hanging. AB - AIM: To study the incidence and outcome of pulmonary edema in patients admitted with near hanging. MATERIALS: A retrospective analysis of 19 cases of near hanging admitted in our Emergency Department between January 2007 and December 2010 was performed. Occurrence of pulmonary edema; electrocardiographic changes; ejection fraction on echocardiography, cardiac enzymes, mechanical ventilation; and use of inotropes, mannitol, and steroids were noted. RESULTS: Seven patients developed clinical and radiologic pulmonary edema, among whom three had electrocardiographic and echocardiographic changes that resolved before discharge. Use of mannitol precipitated edema in four, while inotropes and mechanical ventilation were instituted in three patients. CONCLUSION: Pulmonary edema can be due to neurogenic, cardiogenic, postobstructive causes or an interplay of the three. Takotsubo cardiomyopathy/myocardial stunning related pulmonary edema seems more common than the others. Pulmonary edema occurred irrespective of level of consciousness or electrocardiographic changes and was not associated with mortality. Victims of near hanging with pulmonary edema can be effectively treated with supportive therapy. PMID- 22310140 TI - Percutaneous extraction of deeply-embedded radiopaque foreign bodies using a less invasive technique under image guidance. AB - BACKGROUND: Radiopaque foreign bodies (RFBs) retained in soft tissue are a common clinical problem. Image-guided extraction plays a great role in this realm. We describe our experience in the management of RFBs imbedded deeply in soft tissue using a percutaneous less-invasive technique under fluoroscopic guidance. METHODS: In all, 76 patients with 251 RFBs including gun pellets (n = 223), needle fragments (n = 4), and irregular metallic splinters (n = 24) underwent percutaneous extraction of RFBs with the modified technique, which consists of: (1) percutaneously gaining access to the RFB using an 18-gauge needle, several tapered dilators, and an outer cannula and (2) grasping and withdrawal of RFB using a forceps through the cannula. The following periods were 6 months to 6 years. RESULTS: The direct distance between RFB and skin was from 2.5 cm to 8.5 cm (average 4.8 cm). Every RFB was successfully removed with technique success rate of 100%. The RFBs measured 0.2 cm to 3.0 cm in length and 0.1 cm to 0.5 cm in width. The procedural time and exposure time of X-ray for each RFB extraction were 8 minutes to 15 minutes and 1 minute to 4 minutes (mean, 10 minutes and 2 minutes, respectively). The radiation doses for each RFB and patient were 15.64 mGy to 62.56 mGy and 15.64 mGy to 500.48 mGy (mean, 30.26 mGy and 72.47 mGy, respectively). Blood lead concentration decreased to normal one month after the procedures in four patients with preprocedural high level. No complications were observed during the procedures and the following periods. CONCLUSION: Percutaneous extraction of RFBs from deep soft tissue with the present technique is safe, effective, and minimally invasive. PMID- 22310141 TI - Deck-slap injuries. PMID- 22310143 TI - Improved survival after hemostatic resuscitation. PMID- 22310145 TI - Trauma and massive hemorrhage: back to the future... again. PMID- 22310150 TI - Reduced metabotropic glutamate receptor 5 in the Flinders Sensitive Line of rats, an animal model of depression: an autoradiographic study. AB - Depression is a brain disorder and there is still only a partial understanding of its underlying pathophysiology. Antidepressant medications with a fast onset have not yet been developed. In addition to the monoaminergic systems, the brain glutaminergic system has been implicated in the etiology of depression. Animal studies of depression have gained importance because they permit a more invasive manipulation of the subjects than human studies. In the present study, we measured the densities of the brain regional metabotropic glutaminergic receptor 5 (mGluR5) in the Flinders Sensitive Line (FSL) rat model of depression and two groups of control rats, the Flinders Resistant Line (FRL) and Sprague Dawley (SPD), the parent strain for both the FSL and FRL rats. The FSL rats showed lower densities of mGluR5 in many brain regions compared to either the SPD and/or FRL rats. In addition, the densities in the FRL rats were larger than in the SPD rats, suggesting possible problems in using FRL rats as controls. The presented data suggest that mGluR5 is lower in animal models of depression which could be related to the cognitive and emotional dysfunctions in the FSL rat model of depression and could be relevant to a better understanding of depression in humans. PMID- 22310151 TI - Abrasions of the outer silicone insulation of endocardial leads in their intracardiac part: a new mechanism of lead-dependent endocarditis. AB - AIMS: The aim of the study was to identify and characterize the morphology of abrasions and to establish the frequency of the phenomena and their association with infective endocarditis (IE). METHODS AND RESULTS: A total of 212 endocardial leads removed from 141 consecutive patients-due to IE (32), pocket infection (37), and non-infective indications (72)-were analysed with a stereomicroscope and a scanning electron microscope. The presence of abrasions in the intracardiac part (IP) of the atrial (P < 0.01) and ventricular (P < 0.00002) leads, regardless of its advancement, was strongly associated with IE. There were associations between abrasions in the IP of the ventricular (P < 0.00002) and atrial (P < 0.005) leads and two or more implanted endocardial leads. In atrial leads, there was an association between the presence of any abrasion and passive fixation (P < 0.05), dwell time (P < 0.05), and number of procedures until removal (P < 0.006). The abrasions were classified into three levels of degradation under two subtypes according to the morphology observed with a stereomicroscope. The third level of degradation was the most frequently observed in the IP of the leads. CONCLUSIONS: The abrasion of the outer insulation in the IP of silicone leads was significant regardless of the level of degradation and is associated with IE. The abrasions observed in the IP of the leads were similar to those observed in the intravenous and pocket parts, with predomination of the third level of degradation. There was an association between the presence of any abrasion in the IP of the leads and the number of leads, and in the case of atrial leads between abrasions and fixation type, dwell time, and number of procedures until explantation. PMID- 22310152 TI - Atrial fibrillation: is there evidence to support an early ablation strategy? PMID- 22310153 TI - Optimization of the atrioventricular delay in sequential and biventricular pacing: physiological bases, critical review, and new purposes. AB - Atrioventricular (AV) delay optimization in sequential and biventricular (BiV) pacing, although widely recommended, is often poorly performed in clinical practice as an improper setting can reduce the success of the stimulation. Despite the several methods proposed, the AV delay is frequently programmed in an empirical way or left to a predefined value (usually the manufacturer's setting), without considering the different variables involved in this context, concerning the intra- and interindividual variability of the electromechanical events, the peculiarities of the several cardiopathies, the spontaneous interatrial and AV conduction, the pharmacological therapy, and the pacing mode. The manuscript illustrates the physiological bases of the optimization, describes why and how to programme the best AV delay at rest and during daily activities and discusses critically all methods proposed, divided into three groups: predefined formulas, iterative attempts, and automatic settings. The manuscript is not only a review because it tries to clarify this complex topic, stating the fundamental concept in BiV pacing; the optimal AV delay should be short enough to have always a pre exitated stimulation and contemporary an optimal left ventricular filling. The paper suggests new purposes and new solutions for this goal, it shows the limits of the actual guidelines and the disappointing results obtained in several studies by automatic methods, goading to find new algorithms. PMID- 22310154 TI - Prior antiarrhythmic drug use and the outcome of atrial fibrillation ablation. AB - AIMS: Atrial fibrillation (AF) ablation is generally performed after patients fail antiarrhythmic drug (AAD) therapy. Some patients have drug contraindications or choose to avoid a lifetime of drug therapy. Little is known about the impact of previous drug therapy on ablation outcomes. We evaluated AAD use before AF ablation and its impact on ablation outcomes. METHODS AND RESULTS: We evaluated freedom from AF after ablation and patients' clinical characteristics by number of AADs failed in 1125 patients undergoing 1504 ablations. We also evaluated reasons why some patients did not receive prior drug therapy. Cox multivariate analysis examined factors predicting ablation failure. Patients failing more drugs before ablation were older (P = 0.001), had a longer duration of AF (P = 0.0001), were more likely female (P = 0.037), had more repeat ablations (P = 0.045), and less paroxysmal AF (P = 0.003). For patients with either paroxysmal or persistent AF, the number of drugs failed predicted AF recurrence (P = 0.0001). Other factors predicting AF recurrence following final ablation included age (P = 0.004), left atrial size (P = 0.002), female gender (P = 0.0001), and persistent AF (P = 0.0001). The reason for not receiving prior drug therapy was medical in 21.5% and patient choice in 78.5%. Number of drugs failed did not influence ablation outcome for patients with long-standing persistent AF (P = 0.352). CONCLUSIONS: For paroxysmal and persistent AF patients undergoing ablation, those failing fewer AADs have different clinical characteristics than those who fail more drugs. Our study also suggests that the more drugs failed pre ablation, the lower the freedom from AF post-procedure, possibly due to AF progression during drug trials. PMID- 22310155 TI - Electrochemical approach for acute myocardial infarction diagnosis based on direct antibodies-free analysis of human blood plasma. AB - A novel direct antibodies-free electrochemical approach for acute myocardial infarction (AMI) diagnosis has been developed. For this purpose, a combination of the electrochemical assay of plasma samples with chemometrics was proposed. Screen printed carbon electrodes modified with didodecyldimethylammonium bromide were used for plasma charactrerization by cyclic (CV) and square wave voltammetry and square wave (SWV) voltammetry. It was shown that the cathodic peak in voltammograms at about -250 mV vs. Ag/AgCl can be associated with AMI. In parallel tests, cardiac myoglobin and troponin I, the AMI biomarkers, were determined in each sample by RAMP immunoassay. The applicability of the electrochemical testing for AMI diagnostics was confirmed by statistical methods: generalized linear model (GLM), linear discriminant analysis (LDA) and quadratic discriminant analysis (QDA), artificial neural net (multi-layer perception, MLP), and support vector machine (SVM), all of which were created to obtain the "True False" distribution prediction where "True" and "False" are, respectively, positive and negative decision about an illness event. PMID- 22310156 TI - Enhanced detection sensitivity of pegylated CdSe/ZnS quantum dots-based prostate cancer biomarkers by surface plasmon-coupled emission. AB - We demonstrate the fabrication and detection of quantum dots (QDs)-based prostate specific antigens (PSAs) cancer protein biochips by using enhanced surface plasmon-coupled emission measurements (SPCE). The PSAs are immobilized on a SiO(2)-protected thin gold substrate and pegylated QDs which conjugated with antibodies of PSA are used as fluorescent probes. Due to the excellent brightness of the QDs and the high directionality of emission, as well as the high light collection efficiency of SPCE, the limit of detection (LOD) is down to 10 fg/mL (equal to 0.3 fM) for the PSA chips by using QDs-based cancer protein. We expect that this QDs-based SPCE measurement system with the low LOD supplies a great potential for detecting various cancer biomarkers that are present in only low concentrations within the human body. PMID- 22310157 TI - Acoustic wave based MEMS devices for biosensing applications. AB - This paper presents a review of acoustic-wave based MEMS devices that offer a promising technology platform for the development of sensitive, portable, real time biosensors. MEMS fabrication of acoustic wave based biosensors enables device miniaturization, power consumption reduction and integration with electronic circuits. For biological applications, the biosensors are integrated in a microfluidic system and the sensing area is coated with a biospecific layer. When a bioanalyte interacts with the sensing layer, mass and viscosity variations of the biospecific layer can be detected by monitoring changes in the acoustic wave properties such as velocity, attenuation, resonant frequency and delay time. Few types of acoustic wave devices could be integrated in microfluidic systems without significant degradation of the quality factor. The acoustic wave based MEMS devices reported in the literature as biosensors and presented in this review are film bulk acoustic wave resonators (FBAR), surface acoustic waves (SAW) resonators and SAW delay lines. Different approaches to the realization of FBARs, SAW resonators and SAW delay lines for various biochemical applications are presented. Methods of integration of the acoustic wave MEMS devices in the microfluidic systems and functionalization strategies will be also discussed. PMID- 22310158 TI - Lung imaging - two dimensional gamma scintigraphy, SPECT, CT and PET. AB - This review will cover the principles of imaging the deposition of inhaled drugs and some of the state-of-the art imaging techniques being used today. Aerosol deposition can be imaged and quantified by the addition of a radiolabel to the aerosol formulation. The subsequent imaging of the inhaled deposition pattern can be acquired by different imaging techniques. Specifically, this review will focus on the use of two-dimensional planar, gamma scintigraphy, SPECT, CT and PET. This review will look at how these imaging techniques are used to investigate the mechanisms of drug delivery in the lung and how the lung anatomy and physiology have the potential to alter therapeutic outcomes. PMID- 22310159 TI - A magnificent journey. PMID- 22310160 TI - Calcium phosphate cements as drug delivery materials. AB - Calcium phosphate cements are used as synthetic bone grafts, with several advantages, such as their osteoconductivity and injectability. Moreover, their low-temperature setting reaction and intrinsic porosity allow for the incorporation of drugs and active principles in the material. It is the aim of the present work to: a) provide an overview of the different approaches taken in the application of calcium phosphate cements for drug delivery in the skeletal system, and b) identify the most significant achievements. The drugs or active principles associated to calcium phosphate cements are classified in three groups, i) low molecular weight drugs; ii) high molecular weight biomolecules; and iii) ions. PMID- 22310161 TI - Synthesis of [1,2,4]-triazolo-annulated 3-aza-A-homocholestanes--a novel class of pentacyclic compounds. AB - This study was performed to investigate the reactivity of azocarbenium salts derived from 5alpha-cholestan-3-one towards 1,3-dipolar cycloaddition reactions with inverse electron-demand to produce unprecedented steroidal heterocyclic derivatives, i.e. [1,2,4]-triazolo-annulated 3-aza-A-homocholestanes 8 and 11 and picrates 12. The synthetic steps were comprised of oxidizing hydrazones 3 with tert-butyl hypochlorite to germinal chloroazo compounds 4, generation of the 1 aza-2-azoniaallene cations 5 by action with equimolar antimony pentachloride and interception with nitrile and alkyne molecules by cycloaddition to the triple bond followed by ring enlargement. The structure of the compounds was principally established on the basis of the analytical and spectral data along with the previously published X-ray diffraction analysis on 8a. PMID- 22310162 TI - Age, photoperiod and estrogen dependent variations in the shell gland and the expression of AVT in the ovary of Japanese quail. AB - Present work was undertaken to describe (i) age dependent (prepuberal-3, 4, 5 and 6 weeks old, puberal and actively laying 8 and 12 weeks old and aged 78 weeks old) (ii) photoperiodic response dependent (photosensitive and photorefractory) and sex steroid dependent (estradiol benzoate and its antagonist tamoxifen treated) variation in the ovary and shell gland activity of Japanese quail (Coturnix coturnix japonica). Further, in view of the role of neurohypophysial peptide arginine vasotocin (AVT) in many physiological processes including age/reproduction related oviposition, expression of ir-AVT was also monitored in the ovary of quail. All the parameters associated with histodifferentiation increased rapidly during the developing stages followed by a decrease in old age, which also increased in reproductively quiescent photorefractory birds following estradiol treatment and decreased in reproductively active photosensitive quail following tamoxifen treatment. Using AVT-specific antibody, expression of immunoreactive AVT (ir-AVT) observed in the ovary of photosensitive quail was not detected in the photorefractory quail. However, administration of estrogen in the photorefractory quail stimulated the growth and activity of ovary and shell gland also resulted in the expression of ovarian ir-AVT. On the other hand, tamoxifen eliminated the localization of ir-AVT in the ovary of photosensitive quail in addition to a decrease in the shell gland protein and alkaline phosphatase activity. It is concluded that estrogen not only affects the growth and differentiation of ovary and oviduct including shell gland but also regulates the expression of ovarian AVT. It is also suggested that in addition to reported paracrine effect of AVT in the shell gland of Japanese quail for oviposition, ovarian AVT may also affect ovarian function (ovulation), and in part, this regulation is estrogen dependent. PMID- 22310163 TI - Contemporary postnatal plastic surgical management of meningomyelocele. AB - BACKGROUND: The goals of this study were to review the outcome of the surgical procedure and hospitalization associated with meningomyelocele repair, and to examine the results of different closure strategies. METHODS: Eighty-three consecutive patients having surgery for meningomyelocele over a ten year period form the basis of this study. Thirty-two closures with a mean defect size preoperatively of 11.5 cm(2) were performed by the neurosurgeon (ADP), and fifty one closures with a mean defect size of 28.4 cm(2) by the plastic surgeon (MFA). RESULTS: Defects up to 12 cm(2) were closed with local advancement fasciocutaneous flaps. As defect size increased, latissimus muscle flaps were added in 30 (36%) and gluteus muscle in 16 (19%). In recent years, 18 patients (21.6%) with a mean defect of 29 cm(2) were treated with overlapping of deepithelialized fasciocutaneous flaps to add an additional layer of coverage to the dural closure. There were 9 major complications, 6 requiring reoperation. There were 10 minor wound failures managed conservatively. Mean hospital stay was 24.2 days. Re-operation increased length of stay to 45 days (p < 0.0001). Minor wound problems added 6 days to mean hospital stay. Wound failure did not correlate with either defect size or closure technique. Thoracic location was associated with increased wound failure (p < 0.05). Use of a shunt did not increase morbidity. All closures remained durable after discharge. CONCLUSIONS: Location in the thoracic area predicts major wound failure and need for reoperation. Wound complications significantly increase hospital stay. The use of a variety of techniques to achieve multi-layered closures leads to durable coverage for defects of all sizes. PMID- 22310164 TI - Effects of Bluetooth device electromagnetic field on hearing: pilot study. AB - BACKGROUND: The Bluetooth wireless headset has been promoted as a 'hands-free' device with a low emission of electromagnetic radiation. OBJECTIVE: To evaluate potential changes in hearing function as a consequence of using Bluetooth devices, by assessing changes in pure tone audiography and distortion production otoacoustic emissions. DESIGN: Prospective study. MATERIALS AND METHODS: Thirty adult volunteers were exposed to a Bluetooth headset device (1) on 'standby' setting for 6 hours and (2) at full power for 10 minutes. Post-exposure hearing was evaluated using pure tone audiography and distortion production otoacoustic emission testing. RESULTS: There were no statistically significant changes in hearing, as measured above, following either exposure type. CONCLUSION: Exposure to the electromagnetic field emitted by a Bluetooth headset, as described above, did not decrease hearing thresholds or alter distortion product otoacoustic emissions. PMID- 22310165 TI - Etiological relationships of parotid saliva cyclic nucleotides in patients with taste and smell dysfunction. AB - OBJECTIVE: We previously demonstrated that parotid saliva cAMP and cGMP were lower in patients with taste and smell dysfunction than in normal subjects. We subsequently demonstrated parotid saliva cAMP and cGMP were inversely correlated with smell loss degree such that as smell loss severity increased parotid saliva cAMP and cGMP decreased proportionately. To learn more about these relationships we studied parotid saliva cAMP and cGMP with respect to aetiology of sensory loss in these patients. DESIGN: Parotid saliva cAMP and cGMP in patients with smell loss (hyposmia) who participated in an open label fixed design controlled clinical trial with treatment with oral theophylline were evaluated with respect to their initial etiological diagnosis. Levels of cyclic nucleotides in each etiological category were compared to each other, to the entire patient group and to normal subjects. RESULTS: Mean cAMP and cGMP in all patients combined were below those in normals, as previously described. However, categorized by aetiology, there was a stratification of levels of both cyclic nucleotides; some levels were below the normal mean and some were at or above the normal mean. CONCLUSIONS: Parotid saliva cyclic nucleotides characterised in hyposmic patients by aetiology indicate (1) there are differential alterations in these nucleotides related to aetiology of sensory dysfunction and (2) these moieties measured prior to treatment indicate which patient groups may benefit from treatment with phosphodiesterase (PDE) inhibitors which increase levels of these moieties and thereby correct their sensory dysfunction. PMID- 22310166 TI - The sesquiterpenes beta-caryophyllene and caryophyllene oxide isolated from Senecio salignus act as phytogrowth and photosynthesis inhibitors. AB - The n-hexane extract of S. salignus plants inhibited ATP synthesis and two sesquiterpenes, the beta-caryophyllene (1) and caryophyllene oxide (2) were isolated from this nonpolar fraction. Compound 1 inhibited by 42% the root elongation of Physalis ixocarpa seedlings at 50 ug/mL and by 53% at 150 ug/mL, whereas at 150 ug/mL this compound only inhibited root elongation of Echinochloa crus-galli by 30%. On the other hand, compound 2 had no effect on either germination or root and stem growth of E. cruss galli and P. ixocarpa. However, 1 and 2 inhibited the dry biomass of P. ixocarpa plants grown for 18 days previous to treatment and it was found that 1 was the most active biomass inhibitor. The Chl a fluorescence transient in vivo experiment indicates that 1 (100 ug/mL) has a major effect at 72 h after treatment on leaves of P. ixocarpa plants by inhibiting photosystem II (PS II) transforming active reaction centers to "heat sinks" or the formation of silent reaction centers unable to reduce Q(A). beta Caryophyllene also induces chlorosis on treated leaves. PMID- 22310167 TI - Communic acids: occurrence, properties and use as chirons for the synthesis of bioactive compounds. AB - Communic acids are diterpenes with labdane skeletons found in many plant species, mainly conifers, predominating in the genus Juniperus (fam. Cupresaceae). In this review we briefly describe their distribution and different biological activities (anti- bacterial, antitumoral, hypolipidemic, relaxing smooth muscle, etc.). This paper also includes a detailed explanation of their use as chiral building blocks for the synthesis of bioactive natural products. Among other uses, communic acids have proven useful as chirons for the synthesis of quassinoids (formal), abietane antioxidants, ambrox and other perfume fixatives, podolactone herbicides, etc., featuring shorter and more efficient processes. PMID- 22310168 TI - A method of hepatocyte extraction conjugated with HPLC is established for screening potential active components in Chinese medicines--probing Herba Artemisiae Scopariae as an exemplifying approach. AB - In order to establish an effective and quick method for screening potential bioactive compounds in Traditional Chinese Medicines (TCMs), hepatocytes were employed for extracting either bifendate, a clinical medicine for liver diseases, or chemicals in Herba Artemisiae Scopariae (A. Scopariae), a commonly used traditional Chinese medicine for remedying liver diseases such as hepatitis induced by viruses, chemicals or alcohol. After hepatocyte extraction the compounds were analyzed by HPLC, therefore this method was referrred to as hepatocyte extraction conjugated with HPLC (HE-HPLC). In the first part of this study, HE-HPLC showed that bifendate was extracted by hepatocytes and detected by HPLC-DAD which indicated the feasibility of this method. Then in the second part of the study, the potential active components in the A. scopariae extract were studied using HE-HPLC. Six chemicals in the A. scopariae extract, which could bind to hepatocytes in vitro, were detected by HPLC-DAD and three were identified as 7-hydroxy-coumarin (7-OH-C), capillartemisin A and 7-methoxy-coumarin, respectively. In vitro assays showed that 7-OH-C protected HL-7702 hepatocytes from H2O2 injury. The results indicated that these compounds could be extracted by hepatocytes, could be detected by HPLC and more importantly were bioactive. It is suggested that HE-HPLC is a useful method for screening potent active components in Chinese medicines used to treat liver diseases. PMID- 22310169 TI - Seasonal variation in biomarkers in blue mussel (Mytilus edulis), Icelandic scallop (Chlamys islandica) and Atlantic cod (Gadus morhua): implications for environmental monitoring in the Barents Sea. AB - In the Barents Sea, the limited data on biological relevant indicators and their responses to various anthropogenic stressors have hindered the development of a consistent scientific basis for selecting indicator species and developing practical procedures for environmental monitoring. Accordingly, the main aim of the present study was to develop a common set of baseline values for contaminants and biomarkers in three species, and to identify their strengths and limitations in monitoring of the Barents Sea. Blue mussel (Mytilus edulis), Icelandic scallop (Chlamys islandica) and Atlantic cod (Gadus morhua) were sampled from a north Norwegian fjord in March, June, September and December 2010. Digestive glands from the bivalve species and liver from Atlantic cod were analysed for biomarkers of oxidative stress (catalase [CAT], glutathione peroxidase [GPX], glutathione-S transferase activities [GST], lipid peroxidation as thiobarbituric reactive substances [TBARS] and total oxyradical scavenging capacity [TOSC]), biotransformation (ethoxyresorufine-O-deethylase activity [EROD]) and general stress (lysosomal membrane stability [LMS]). Concentrations of polycyclic aromatic hydrocarbons (PAHs) and metals in the bivalves and PAH metabolites in fish bile were quantified. Finally, energy reserves (total lipids, proteins and carbohydrates) and electron transport system (ETS) activity in the digestive gland of the bivalves and liver of Atlantic cod provided background information for reproductive cycle and general physiological status of the organisms. Blue mussel and Icelandic scallop showed very similar trends in biological cycle, biomarker expression and seasonality. Biomarker baselines in Atlantic cod showed weaker seasonal variability. However, important biological events may have been undetected due to the large time intervals between sampling occasions. Physiological biomarkers such as energy reserves and ETS activity were recommended as complementary parameters to the commonly used stress biomarkers, as they provided valuable information on the physiological status of the studied organisms. Interpretation of the seasonality in oxidative stress biomarkers was in general difficult but TOSC and lipid peroxidation were preferred over the antioxidant enzyme activities. This study is the first reporting seasonal baseline in these three species in a sub-Arctic location. Overall, the Icelandic scallop was considered the most adequate organism for environmental monitoring in the Barents Sea due to the interpretability of the biomarker data as well as its abundance, ease to handle and wide distribution from the southern Barents Sea to Svalbard. PMID- 22310170 TI - Drought episode modulates the response of river biofilms to triclosan. AB - The consequences of global change on rivers include altered flow regime, and entrance of compounds that may be toxic to biota. When water is scarce, a reduced dilution capacity may amplify the effects of chemical pollution. Therefore, studying the response of natural communities to compromised water flow and to toxicants is critical for assessing how global change may affect river ecosystems. This work aims to investigate how an episode of drought might influence the response of river biofilms to pulses of triclosan (TCS). The objectives were to assess the separate and combined effects of simulated drought (achieved through drastic flow alteration) and of TCS exposure on biofilms growing in artificial channels. Thus, three-week-old biofilms were studied under four conditions: Control (normal water flow); Simulated Drought (1 week reduced flow+2 days interrupted flow); TCS only (normal water flow plus a 48-h pulse of TCS); and Simulated Drought+TCS. All channels were then left for 2 weeks under steady flow conditions, and their responses and recovery were studied. Several descriptors of biofilms were analyzed before and after each step. Flow reduction and subsequent interruption were found to provoke an increase in extracellular phosphatase activity, bacterial mortality and green algae biomass. The TCS pulses severely affected biofilms: they drastically reduced photosynthetic efficiency, the viability of bacteria and diatoms, and phosphate uptake. Latent consequences evidenced significant combined effects caused by the two stressors. The biofilms exposed only to TCS recovered far better than those subjected to both altered flow and subsequent TCS exposure: the latter suffered more persistent consequences, indicating that simulated drought amplified the toxicity of this compound. This finding has implications for river ecosystems, as it suggests that the toxicity of pollutants to biofilms may be exacerbated following a drought. PMID- 22310171 TI - Possession by 'Jinn' as a cause of epilepsy (Saraa): a study from Saudi Arabia. AB - PURPOSE: Epilepsy has been linked to divine, demonic and supernatural powers throughout its long history. This study was conducted to explore if misconceptions such as possession by demons (Jinns) are still believed to be a cause of epilepsy among educated Saudis today. METHOD: This study was conducted among university-educated school teachers and undergraduate students. The findings are based on a structured questionnaire enquiring about familiarity with epilepsy, sources of knowledge, and depth of knowledge about specific aspects of epilepsy. RESULTS: Responses from 398 participants were included in the analysis of the results. Most participants had witnessed epileptic seizures. 2/3 of the participants reported that they had learned about epilepsy from friends and relatives. 172 (43.1%) members believed that epilepsy is a psychiatric disease. 62 (40.3%) of the school teachers and 123 (50.4%) of the students in the study considered possession as a cause of epilepsy. The majority of the cohort believed medical treatment for the condition exists despite the fact that a significant number believed that faith healers and traditional medicine can be of help in the treatment of epilepsy. CONCLUSION: Jinn possession is still believed to be a cause of epilepsy in Saudi society, even among fairly well-educated people. This finding emphasizes the urgent need for public education campaigns at all levels of education. PMID- 22310172 TI - Stereospecific antioxidant effects of ginsenoside Rg3 on oxidative stress induced by cyclophosphamide in mice. AB - Ginsenoside Rg3 is one of the active ingredients isolated from Panax ginseng C.A. Meyer. Previous investigation demonstrated that Rg3 was stereospecific in promotion of the immune response. The present study was designed to evaluate Rg3 and its epimers, 20(R)-Rg3 and 20(S)-Rg3, for their effects on oxidative stress induced by cyclophosphamide (Cy) in mice. Forty-eight mice were randomly distributed into 6 groups and intraperitoneally administered saline solution, Cy, 20(R)-Rg3, 20(S)-Rg3, 20(R)-Rg3+Cy or 20(S)-Rg3+Cy. After that, the spleen, thymus and serum were collected to measure the indices of the organs and oxidative parameters. The results showed that Rg3 significantly inhibited Cy induced oxidative stress in mice by increasing the indices of the spleen and thymus and total antioxidant capacity, elevating the activities of catalase, superoxidase dismutase and lysozyme as well as decreasing the activity of xanthine oxidase and the levels of malondialdehyde and nitric oxide. Rg3 was stereospecific in antioxidant activities as R form exhibited significantly higher antioxidant effects than S form. Therefore, R form should be used when Rg3 is considered to be used as an antioxidant agent. PMID- 22310173 TI - Nicotine dynamically modulates dopamine clearance in rat striatum in vivo. AB - Nicotine binds to nicotinic acetylcholine receptors on dopaminergic terminals to evoke dopamine (DA) release. The clearance of released DA occurs rapidly through reuptake into nerve terminals through the DA transporter (DAT). However, whether nicotine modulates DAT function in vivo is still not well understood. In the present study, we determined the effect of nicotine on DA clearance using in vivo amperometric recording in the striatum of urethane-anesthetized rats. Stable DA release was evoked by electrical stimulation of the medial forebrain bundle (MFB). Subsequently, nicotine or saline was administered with MFB stimulation at 10-min intervals for 60 min. Kinetic analysis revealed that nicotine decreased the amplitude of DA overflow and the maximal DA clearance rate (V(max)) in response to stimulation of 96 pulses at 80 Hz. Surprisingly, nicotine enhanced the maximal DA clearance rate (V(max)) by stimulation of 768 pulses at 80 Hz. Furthermore, we found that this paradoxical effect of nicotine on V(max) depended on the stimulation pattern. These results suggest that nicotine may exert its addictive role by dynamically modulating DAT function in vivo. PMID- 22310174 TI - Engineering microbial systems to explore ecological and evolutionary dynamics. AB - A major goal of biological research is to provide a mechanistic understanding of diverse biological processes. To this end, synthetic biology offers a powerful approach, whereby biological questions can be addressed in a well-defined framework. By constructing simple gene circuits, such studies have generated new insights into the design principles of gene regulatory networks. Recently, this strategy has been applied to analyze ecological and evolutionary questions, where population-level interactions are critical. Here, we highlight recent development of such systems and discuss how they were used to address problems in ecology and evolutionary biology. As illustrated by these examples, synthetic ecosystems provide a unique platform to study ecological and evolutionary phenomena that are challenging to study in their natural contexts. PMID- 22310175 TI - Development of monoclonal antibodies to human microsomal epoxide hydrolase and analysis of "preneoplastic antigen"-like molecules. AB - Microsomal epoxide hydrolase (mEH) is a drug metabolizing enzyme which resides on the endoplasmic reticulum (ER) membrane and catalyzes the hydration of reactive epoxide intermediates that are formed by cytochrome P450s. mEH is also thought to have a role in bile acid transport on the plasma membrane of hepatocytes. It is speculated that efficient execution of such multiple functions is secured by its orientation and association with cytochrome P450 enzymes on the ER membrane and formation of a multiple transport system on the plasma membrane. In certain disease status, mEH loses its association with the membrane and can be detected as distinct antigens in the cytosol of preneoplastic foci of liver (preneoplastic antigen), in the serum in association with hepatitis C virus infection (AN antigen), or in some brain tumors. To analyze the antigenic structures of mEH in physiological and pathological conditions, we developed monoclonal antibodies against different portions of mEH. Five different kinds of antibodies were obtained: three, anti-N-terminal portions; one anti-C-terminal; and one, anti conformational epitope. By combining these antibodies, we developed antigen detection methods which are specific to either the membrane-bound form or the linearized form of mEH. These methods detected mEH in the culture medium released from a hepatocellular carcinoma cell line and a glioblastoma cell line, which was found to be a multimolecular complex with a unique antigenic structure different from that of the membrane-bound form of mEH. These antibodies and antigen detection methods may be useful to study pathological changes of mEH in various human diseases. PMID- 22310176 TI - In vitro toxicological effects of estrogenic mycotoxins on human placental cells: structure activity relationships. AB - Zearalenone (ZEN) is a non-steroid estrogen mycotoxin produced by numerous strains of Fusarium which commonly contaminate cereals. After oral administration, ZEN is reduced via intestinal and hepatic metabolism to alpha- and beta-zearalenol (alphaZEL and betaZEL). These reduced metabolites possess estrogenic properties, alphaZEL showing the highest affinity for ERs. ZEN and reduced metabolites cause hormonal effects in animals, such as abnormalities in the development of the reproductive tract and mammary gland in female offspring, suggesting a fetal exposure to these contaminants. In our previous work, we have suggested the potential impact of ZEN on placental cells considering this organ as a potential target of xenobiotics. In this work, we first compared the in vitro effects of alphaZEL and betaZetaEpsilonL on cell differentiation to their parental molecule on human trophoblast (BeWo cells). Secondly, we investigated their molecular mechanisms of action by investigating the expression of main differentiation biomarkers and the implication of nuclear receptor by docking prediction. Conversely to ZEN, reduced metabolites did not induce trophoblast differentiation. They also induced significant changes in ABC transporter expression by potential interaction with nuclear receptors (LXR, PXR, PR) that could modify the transport function of placental cells. Finally, the mechanism of ZEN differentiation induction seemed not to involve nuclear receptor commonly involved in the differentiation process (PPARgamma). Our results demonstrated that in spite of structure similarities between ZEN, alphaZEL and betaZEL, toxicological effects and toxicity mechanisms were significantly different for the three molecules. PMID- 22310177 TI - Relative sensitivity of developmental and immune parameters in juvenile versus adult male rats after exposure to di(2-ethylhexyl) phthalate. AB - The developing immune system displays a relatively high sensitivity as compared to both general toxicity parameters and to the adult immune system. In this study we have performed such comparisons using di(2-ethylhexyl) phthalate (DEHP) as a model compound. DEHP is the most abundant phthalate in the environment and perinatal exposure to DEHP has been shown to disrupt male sexual differentiation. In addition, phthalate exposure has been associated with immune dysfunction as evidenced by effects on the expression of allergy. Male wistar rats were dosed with corn oil or DEHP by gavage from postnatal day (PND) 10-50 or PND 50-90 at doses between 1 and 1000 mg/kg/day. Androgen-dependent organ weights showed effects at lower dose levels in juvenile versus adult animals. Immune parameters affected included TDAR parameters in both age groups, NK activity in juvenile animals and TNF-alpha production by adherent splenocytes in adult animals. Immune parameters were affected at lower dose levels compared to developmental parameters. Overall, more immune parameters were affected in juvenile animals compared to adult animals and effects were observed at lower dose levels. The results of this study show a relatively higher sensitivity of juvenile versus adult rats. Furthermore, they illustrate the relative sensitivity of the developing immune system in juvenile animals as compared to general toxicity and developmental parameters. This study therefore provides further argumentation for performing dedicated developmental immune toxicity testing as a default in regulatory toxicology. PMID- 22310178 TI - H1-antihistamines induce vacuolation in astrocytes through macroautophagy. AB - H1-antihistamines induce vacuolation in vascular smooth muscle cells, which may contribute to their cardiovascular toxicity. The CNS toxicity of H1 antihistamines may also be related to their non-receptor-mediated activity. The aim of this study was to investigate whether H1-antihistamines induce vacuolation in astrocytes and the mechanism involved. The H1-antihistamines induced large numbers of giant vacuoles in astrocytes. Such vacuoles were marked with both the lysosome marker Lysotracker Red and the alkalescent fluorescence dye monodansylcadaverine, which indicated that these vacuoles were lysosome-like acidic vesicles. Quantitative analysis of monodansylcadaverine fluorescence showed that the effect of H1-antihistamines on vacuolation in astrocytes was dose dependent, and was alleviated by extracellular acidification, but aggravated by extracellular alkalization. The order of potency to induce vacuolation at high concentrations of H1-antihistamines (diphenhydramine>pyrilamine>astemizole>triprolidine) corresponded to their pKa ranking. Co-treatment with histamine and the histamine receptor-1 agonist trifluoromethyl toluidide did not inhibit the vacuolation. Bafilomycin A1, a vacuolar (V)-ATPase inhibitor, which inhibits intracellular vacuole or vesicle acidification, clearly reversed the vacuolation and intracellular accumulation of diphenhydramine. The macroautophagy inhibitor 3-methyladenine largely reversed the percentage of LC3-positive astrocytes induced by diphenhydramine, while only partly reversing the number of monodansylcadaverine-labeled vesicles. In Atg5-/- mouse embryonic fibroblasts, which cannot form autophagosomes, the number of vacuoles induced by diphenhydramine was less than that in wild-type cells. These results indicated that H1-antihistamines induce V-ATPase-dependent acidic vacuole formation in astrocytes, and this is partly mediated by macroautophagy. The pKa and alkalescent characteristic of H1-antihistamines may be the major determinants of vacuolation, which may contribute to their CNS toxicity. PMID- 22310179 TI - Oroxylin A reverses CAM-DR of HepG2 cells by suppressing Integrinbeta1 and its related pathway. AB - Oroxylin A, a naturally occurring monoflavonoid extracted from Scutellariae radix, shows effective anticancer activities and low toxicities both in vivo and in vitro in previous studies. In this study, we investigated whether the CAM-DR model of HepG2 cells showed resistance to cytotoxic agents compared with normally cultured HepG2 cells. Furthermore, after the treatment of Paclitaxel, less inhibitory effects and decreased apoptosis rate were detected in the model. Data also revealed increased expression of Integrinbeta1 might be responsible for the resistance ability. Moreover, Integrinbeta1-siRNA-transfected CAM-DR HepG2 cells exhibited more inhibitory effects and higher levels of apoptosis than the non transfected CAM-DR cells. The data corroborated that Integrinbeta1 played a significant role in CAM-DR. After the treatment of weakly-toxic concentrations of Oroxylin A, the apoptosis induced by Paclitaxel in the CAM-DR model increased dramatically. Western blot assay revealed Oroxylin A markedly down-regulated the expression of Integrinbeta1 and the activity of related pathway. As a conclusion, Oroxylin A can reverse the resistance of CAM-DR via inhibition of Integrinbeta1 and its related pathway. Oroxylin A may be a potential candidate of a CAM-DR reversal agent. PMID- 22310180 TI - The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: synergism with the benzodiazepine diazepam. AB - Therapy of seizure activity following exposure to the nerve agent soman (GD) includes treatment with the anticonvulsant diazepam (DZP), an allosteric modulator of gamma-aminobutyric acid A (GABA(A)) receptors. However, seizure activity itself causes the endocytosis of GABA(A) receptors and diminishes the inhibitory effects of GABA, thereby reducing the efficacy of DZP. Treatment with an N-methyl-d-aspartic acid (NMDA) receptor antagonist prevents this reduction in GABAergic inhibition. We examined the efficacy of the NMDA receptor antagonist caramiphen edisylate (CED; 20mg/kg, im) and DZP (10mg/kg, sc), administered both separately and in combination, at 10, 20 or 30min following seizure onset for attenuation of the deleterious effects associated with GD exposure (1.2 LD(50); 132MUg/kg, sc) in rats. Outcomes evaluated were seizure duration, neuropathology, acetylcholinesterase (AChE) activity, body weight, and temperature. We also examined the use of the reversible AChE inhibitor physostigmine (PHY; 0.2mg/kg, im) as a therapy for GD exposure. We found that the combination of CED and DZP yielded a synergistic effect, shortening seizure durations and reducing neuropathology compared to DZP alone, when treatment was delayed 20-30min after seizure onset. PHY reduced the number of animals that developed seizures, protected a fraction of AChE from GD inhibition, and attenuated post-exposure body weight and temperature loss independent of CED and/or DZP treatment. We conclude that: 1) CED and DZP treatment offers considerable protection against the effects of GD and 2) PHY is a potential therapeutic option following GD exposure, albeit with a limited window of opportunity. PMID- 22310181 TI - Mangiferin exerts hepatoprotective activity against D-galactosamine induced acute toxicity and oxidative/nitrosative stress via Nrf2-NFkappaB pathways. AB - Mangiferin, a xanthone glucoside, is well known to exhibit antioxidant, antiviral, antitumor, anti-inflammatory and gene-regulatory effects. In the present study, we isolated mangiferin from the bark of Mangifera indica and assessed its beneficial role in galactosamine (GAL) induced hepatic pathophysiology. GAL (400 mg/kg body weight) exposed hepatotoxic rats showed elevation in the activities of serum ALP, ALT, levels of triglycerides, total cholesterol, lipid-peroxidation and reduction in the levels of serum total proteins, albumin and cellular GSH. Besides, GAL exposure (5 mM) in hepatocytes induced apoptosis and necrosis, increased ROS and NO production. Signal transduction studies showed that GAL exposure significantly increased the nuclear translocation of NFkappaB and elevated iNOS protein expression. The same exposure also elevated TNF-alpha, IFN-gamma, IL-1beta, IL-6, IL-12, IL-18 and decreased IL 10 mRNA expressions. Furthermore, GAL also decreased the protein expression of Nrf2, NADPH:quinine oxidoreductase-1, heme oxygenase-1 and GSTalpha. However, mangiferin administration in GAL intoxicated rats or coincubation of hepatocytes with mangiferin significantly altered all these GAL-induced adverse effects. In conclusion, the hepatoprotective role of mangiferin was due to induction of antioxidant defense via the Nrf2 pathway and reduction of inflammation via NFkappaB inhibition. PMID- 22310182 TI - Osteoarthritis: Frzb knockout reveals the complexity of Wnt signaling in joint homeostasis. PMID- 22310184 TI - Connective tissue disease: Trial of SLE therapies in real-world settings. PMID- 22310183 TI - Imaging modalities for the diagnosis of pulmonary hypertension in systemic sclerosis. AB - Patients with systemic sclerosis (SSc) are at considerable risk of developing pulmonary arterial hypertension (PAH). PAH has a dramatic impact on the natural history of the disease and overall survival of the patient. Despite progress made in elucidating the pathogenesis of PAH and introduction of novel therapies, SSc related PAH (SScPAH) remains a devastating disease that responds poorly to therapy. Although early diagnosis is of paramount importance, there are no available validated strategies for assessing SScPAH because reliable evaluation of the structure and function of the right ventricle is difficult owing to its complex geometry. Additionally, myocardial fibrosis might affect cardiac contractility and contribute to heart failure. Modern imaging modalities, such as novel echocardiographic techniques and cardiac MRI, are highly sensitive, quantitative and reproducible methods that allow noninvasive assessment of regional and global myocardial performance without relying on geometric assumptions. In this Review, we examine the imaging modalities currently available, focusing on evolving diagnostic imaging methodologies and their possible clinical implications in the SScPAH setting. PMID- 22310185 TI - Experimental arthritis: NGF promotes synovial nerve sprouting. PMID- 22310186 TI - Bone: RBP-J prevents bone erosion. PMID- 22310187 TI - Osteoarthritis: Metabolomic characterization of metabolic phenotypes in OA. PMID- 22310188 TI - Is target opioid therapy within sight? AB - Control of pain has a central role in patients treatment either in advanced cancer or other terminal illnesses and in acute postsurgical or chronic non malignant diseases. Hospitals should promote programs of research on genetic mechanism, and also biochemical and physiological aspects of pain through highly specialized labs. Opioids are the first choice drugs for moderate to severe chronic pain, especially at the end of life, and among them oral morphine is worldwide recognized by the World Health Organization and by the European Association for Palliative Care as the conventional therapy. Although this general agreement, administration of this class of drugs may be a major medical challenge due to the high effects' variability related to pharmacokinetic and pharmacodynamic parameters, such as absorption, distribution and metabolism, as well as intrinsic efficacy at the receptors involved. For such a reason, optimization of the management regime is not always reached in all the patients. Up to now no one can easily predict which patient will experience side effects or an inadequate pain control. The growing body of evidence concerning a sound genetic background of this human intervariability has prompted research on the field of a personalized therapy, focusing on single nucleotide polymorphisms (SNPs), being the most common and diffuse form of genetic variation. This review has the main goal to report the most promising human genetic polymorphisms involved in opioid treatment, and address the relationship between these polymorphisms and the clinical outcome. PMID- 22310189 TI - Echocardiographic evaluation and N-terminal pro-brain natriuretic peptide measurement of patients hospitalized for heart failure during weaning from mechanical ventilation. AB - BACKGROUND: Weaning patients with heart failure who have required mechanical ventilation remains challenging. We evaluated echocardiographic indexes and N terminal pro-brain natriuretic peptide (NT-proBNP) as markers of acute cardiac dysfunction before and after spontaneous breathing trials (SBT) in such patients to assess their ability to predict subsequent successful extubation. METHODS: Forty-four patients who underwent their first SBT were prospectively included. Plasma levels of NT-proBNP and transthoracic echocardiography indices including cardiac index, E/A ratio and E/Ea ratio were recorded immediately before commencing and just before the end of SBT. RESULTS: Ten patients (22.7%) failed their SBT. No significant difference was observed concerning baseline echocardiographic data and NT-proBNP level between the patients who succeeded the SBT or those that failed. Cardiac index increased significantly at end-SBT in patients who passed (3.3 [3.06-3.77] vs. 3 [2.68-3.3] L/min/m(2), P<0.001), whereas it remained unchanged in those that failed. E/Ea ratio (16.8 [8.5-27.3] vs. 10.7 [6.7-20.5], P=0.006) and NT-proBNP level (8199 [3106-10949] vs. 4200 [1855-7125] pg/mL, P=0.004) increased significantly in those who failed the SBT, in contrast to the weaning success group where they remained unchanged. CONCLUSION: Neither NT-proBNP level nor the studied echocardiographic indices before SBT were able to predict SBT outcome in patients presenting with severe heart failure. Failure to increase the cardiac index and increases in both E/Ea ratio and NT-proBNP levels were seen at end-SBT in patients who failed the SBT, and may reflect failure of myocardial reserve to cope with the stress of SBT. PMID- 22310190 TI - Self-directed deliberate practice with virtual fiberoptic intubation improves initial skills for anesthesia residents. AB - BACKGROUND: Fiberoptic intubation is a core skill in anesthesiology. However, this complex psychomotor skill is challenging to learn in the clinical setting. The goal of this study was to evaluate the Virtual Fiberoptic Intubation (VFI) software as an adjunct to the traditional fibreoptic intubation teaching. METHODS: After informed consent, 23 first year anesthesia residents with no previous experience of fiberoptic intubation were randomized to 2 groups. All subjects received an institutional didactic teaching session. The control group (N.=12) was taught by the usual didactic method only, while the VFI group (N.=11) had the same didactic teaching and also the opportunity to practice with VFI software for one week. Each resident was evaluated on their first oro- and nasotracheal fiberoptic intubations on a mannequin head. Each performance was evaluated by an expert bronchoscopist blinded to the previous type of teaching using a checklist score, a global rating scale (GRS) score and procedural time. RESULTS: The VFI group performed significantly better on the checklist and GRS scores compared to the control group for both the oral and nasal routes (all P<0.05). For procedural time, there was a trend towards faster performance in the VFI group compared to the control group for the oral route (P=0.05). There was no significant difference for procedural time between the VFI and the control groups when fiberoptic intubation was performed nasally (P=0.76). CONCLUSION: Self directed practice using VFI software may improve the initial acquisition of fibreoptic intubation skills for anesthesia residents. PMID- 22310191 TI - Standard vs. point-of-care measurement of fibrinogen: potential impact on clinical decisions. AB - BACKGROUND: Intraoperative major bleeding is a common complication during surgery and can lead to the transfusion of blood products and/or procoagulant drugs. This is a therapeutic challenge, and adherence to guidelines is desirable to preserve blood product resources. The intraoperative administration of fibrinogen concentrate, a pro-coagulant drug, in bleeding patients might reduce the use and therefore the risks associated with blood products. METHODS: In this observational pilot study we determined whether fibrinogen measured by point-of care thromboelastometry (Rotem(r), fibtem-test) would lead to a similar therapeutical decision concerning the administration of fibrinogen concentrate when compared to the standard method (Clauss). RESULTS: Blood samples of 36 patients undergoing major surgery were simultaneously analyzed using both methods. According to the cutoff values of current guidelines based on the standard method, no patient would receive fibrinogen concentrate. In comparison, if point-of-care thromboelastometry were used and its cutoff for fibrinogen applied, 16 patients (44%, P<0.001) would receive fibrinogen concentrate. CONCLUSION: The method used for intraoperative coagulation monitoring has a major impact on therapeutic decisions concerning the use of blood products and/or pro coagulant drugs. If fibrinogen was measured by point-of-care thromboelastometry instead of the standard method according to Clauss, the use of fibrinogen concentrate would increase significantly and less fresh frozen plasma would be administered. PMID- 22310192 TI - Monitors of the hypnotic component of anesthesia - correlation between bispectral index and cerebral state index. AB - BACKGROUND: The current study examines whether analysis of identical EEG data results in a high correlation coefficient of BIS and CSI values during all anesthetic levels and assesses the concordance of both EEG monitors for displaying the level of anesthesia as defined by the manufacturers. METHODS: EEG data of 40 patients undergoing elective surgery under general anesthesia with either sevoflurane/remifentanil or propofol/remifentanil were replayed to an EEG player and reanalysed by a BIS A-2000(r) monitor and a Cerebral State Monitor. Further, research into differences between CSI and BIS index values was performed, e.g., extraction of differences of >= 10 and >= 20 index points and of the EEG length with differing index values. RESULTS: The overall correlation coefficient was 0.68 without significant difference between propofol or sevoflurane group. In 51.8% of all recordings, both EEG monitors agreed in their classification of the anesthetic level. The number and length of differing index pairs was influenced by varying time delays of index calculation and different algorithms of index computation. CONCLUSION: In contrast to previous studies, our current approach combines the following conditions: analysis on basis of identical underlying EEG data from deep to light anesthesia, no guidance of anesthetic administration by one of the EEG-based monitors, avoidance of simultaneous EEG readings and the use of two different anesthetic regimens. Though the result of EEG analysis during anesthesia is similar with both monitors, CSI performance during propofol anesthesia was superior to sevoflurane anesthesia. Consequently, a lower agreement of classification of anesthetic levels between BIS and CSI was reached with the use of sevoflurane. Thus, CSI calculation seems not to be independent from anesthetic agent. PMID- 22310193 TI - A prospective pilot study of platelet function and its relationship with postoperative bleeding in pediatric cardiac surgery. AB - BACKGROUND: Postoperative bleeding is a major problem in pediatric cardiac surgery with cardiopulmonary bypass (CPB). It recognizes a multifactorial cause, inclusive of coagulation factors consumption, hyperfibrinolysis, incomplete heparin reversal, and platelet consumption. Limited information on platelet function is available. This pilot study investigates platelet function changes in pediatric cardiac operations and their relationship with postoperative bleeding. METHODS: A cohort of 22 patients aged four years or less were prospectively analyzed. Besides the usual coagulation tests, they were studied for platelet function at four points in time: preoperative, arrival in the intensive care unit, first and second postoperative day. Platelet function was measured with multiple electrode aggregometry TRAP-test. RESULTS: After the cardiac operation there was a non-significant decrease in platelet function, with 36% of the patients demonstrating increased aggregability. Platelet count demonstrated a significant (P=0.001) decrease related to the CPB duration. The International Normalized Ratio (INR) was significantly (P=0.001) increased after the operation. Postoperative bleeding was associated with the degree of thrombocytopenia (P=0.014), the increase in INR (P=0.001), and the prolongation of the activated partial thromboplastin time (P=0.002). CONCLUSION: In this pilot study, platelet function in pediatric patients undergoing cardiac surgery demonstrates a variable pattern and no association with postoperative bleeding. Confounding factors like age and cyanosis should be addressed with larger patient populations. PMID- 22310194 TI - Transversus abdominis plane block using the loss of resistance to air technique. PMID- 22310195 TI - Prucalopride in a case of severe opioid induced constipation. PMID- 22310196 TI - The importance of adequate identification of structure for the success of ultrasound guided blocks. PMID- 22310197 TI - Pediatric life support courses: can participation be avoided? PMID- 22310198 TI - Computer processed EEG and the exploration of the twilight zone. PMID- 22310199 TI - No need for NMDA-receptor antagonists in women undergoing caesarean section? PMID- 22310200 TI - Quantity without quality? Don't dismiss the value of platelet function testing quite yet. PMID- 22310201 TI - Ultrasound guided phrenic nerve block in the treatment of persistent hiccups (singultus) in the neurosurgical critical patient. PMID- 22310202 TI - When the heart hinders the breath. PMID- 22310203 TI - Comment on "drowning". PMID- 22310204 TI - Toxoplasma gondii immune mapped protein-1 (TgIMP1) is a novel vaccine candidate against toxoplasmosis. AB - Immune mapped protein1 (IMP1) is a new protective protein in apicomplexan parasites, and exists in Toxoplasma gondii. In the present study, a DNA vaccine expressing IMP1 of T. gondii was constructed and the immune response induced in BALB/c mice was evaluated. The coding sequence of IMP1 was inserted into the eukaryotic expression vector pcDNA 3.1(+), resulting a recombinant plasmid pcDNA IMP1, which was used to immunize BALB/c mice intramuscularly. After immunization, the immune response was evaluated using lymphoproliferative assay, and cytokine and antibody measurements. The mice were challenged with tachyzoites of the virulent T. gondii RH strain 14th day after the last immunization to observe the survival time. The results showed that the group immunized with pcDNA-IMP1 developed a high level of specific antibody responses against Escherichia coli expressed recombinant TgIMP1, with high IgG antibody titers, predominance of IgG2a production, a strong lymphoproliferative response, and significant levels of IFN-gamma, IL-2, IL-4 and IL-10 production compared with the control groups. These results demonstrate that pcDNA-IMP1 could elicit strong humoral and Th1 immune responses. Immunized mice showed a significantly (15.8 +/- 6 days) prolonged survival time compared with control mice, which died within 7 days of challenge infection. These results suggest that IMP1 is a promising vaccine candidate against toxoplasmosis. PMID- 22310205 TI - A cluster of nonspecific adverse events in a military reserve unit following pandemic influenza A (H1N1) 2009 vaccination-possible stimulated reporting? AB - BACKGROUND: On February 20, 2010, a 23 year old male Army Reservist (index case) with symptom onset 4 h after receiving inactivated monovalent pandemic 2009 (H1N1) vaccine (MIV) was hospitalized with possible Guillain-Barre syndrome (GBS). Within 1-2 days, 13 reservists from the same unit presented to the emergency department and 14 filed Vaccine Adverse Event Reporting System (VAERS) reports of nonspecific symptoms following MIV. OBJECTIVES: To describe the spectrum of adverse events (AE) among reservists in the unit after MIV and to identify factors contributing to this cluster of reports. METHODS: We reviewed the reservists' VAERS reports and hospital records for demographics, influenza vaccination status, diagnostic results and outcome. All VAERS reports after vaccination from the same MIV lot were also screened. We conducted a survey of unit reservists to identify contributing factors for this cluster. RESULTS: The presumptive diagnosis of GBS in the index case was not confirmed. All other reservists demonstrated normal exam findings and laboratory investigations. VAERS reports following vaccination from the same MIV lot revealed no consistent pattern. Our survey of factors contributing to the cluster was returned by 55 reservists (response rate 28%). AEs following MIV were significantly more often reported by female and black reservists. There was a tendency for concern about the safety of the 2010-2011 seasonal influenza vaccine to be higher for reservists that reported an AE to MIV (p=0.13) or that sought medical attention for their symptoms (p=0.08). CONCLUSIONS: This cluster represents possible stimulated reporting following receipt of inactivated pandemic 2009 (H1N1) vaccine among service personnel. PMID- 22310206 TI - Establishing a novel automated magnetic bead-based method for the extraction of DNA from a variety of forensic samples. AB - Automated systems have been increasingly utilized for DNA extraction by many forensic laboratories to handle growing numbers of forensic casework samples while minimizing the risk of human errors and assuring high reproducibility. The step towards automation however is not easy: The automated extraction method has to be very versatile to reliably prepare high yields of pure genomic DNA from a broad variety of sample types on different carrier materials. To prevent possible cross-contamination of samples or the loss of DNA, the components of the kit have to be designed in a way that allows for the automated handling of the samples with no manual intervention necessary. DNA extraction using paramagnetic particles coated with a DNA-binding surface is predestined for an automated approach. For this study, we tested different DNA extraction kits using DNA binding paramagnetic particles with regard to DNA yield and handling by a Freedom EVO((r))150 extraction robot (Tecan) equipped with a Te-MagS magnetic separator. Among others, the extraction kits tested were the ChargeSwitch((r))Forensic DNA Purification Kit (Invitrogen), the PrepFilerTMAutomated Forensic DNA Extraction Kit (Applied Biosystems) and NucleoMagTM96 Trace (Macherey-Nagel). After an extensive test phase, we established a novel magnetic bead extraction method based upon the NucleoMagTM extraction kit (Macherey-Nagel). The new method is readily automatable and produces high yields of DNA from different sample types (blood, saliva, sperm, contact stains) on various substrates (filter paper, swabs, cigarette butts) with no evidence of a loss of magnetic beads or sample cross-contamination. PMID- 22310207 TI - A mouse model to study the alterations in haemostatic and inflammatory parameters induced by Lonomia achelous caterpillar haemolymph. AB - A mouse model was established to reproduce the haemorrhagic syndrome which occurs in humans after accidental contact with the hairs of the caterpillar Lonomia achelous (LA) and measures the haemostatic and inflammatory alterations that occur as a result of this contact. Mice were injected intradermally with different doses (0.4, 0.8 and 1.6 mg/animal) of L. achelous haemolymph (LAH). Haematological (haemoglobin, haematocrit, platelet count, differential leukocyte count), haemostatic (fibrinogen, plasminogen, factor XIII [FXIII], fibrinolytic activity) and inflammatory parameters (tumour necrosis factor alpha [TNF-alpha], nitric oxide [NO]) were measured at different times up to 48 h. C57BL/6 mice responded to LAH injection, in terms of these parameters, in a manner similar to that seen in humans, whereas the BALB/c mice were unresponsive. In C57BL/6 mice injected with LAH, time course measurements showed: a) a reduction in the haemoglobin, haematocrit, fibrinogen, FXIII and plasminogen levels, b) no effect on the platelet count and c) immediate leukocytosis and an increase in the fibrinolytic activity in plasma. An inflammatory response (TNF-alpha) was observed within 1 h post-injection, followed by a more persistent increase in serum NO. These findings suggest that C57BL/6 mice represent a useful model of the haemorrhagic syndrome observed in humans who have suffered contact with the caterpillar, permitting a deeper understanding of the role of the inflammatory response in the haematological and haemostatic manifestations of this syndrome. PMID- 22310208 TI - Prevalence of cardiovascular pathologies in elderly population living in an industrialized area, compared to a control population residing in a rural area. AB - The development of cardiovascular pathologies is potentially connected to the surrounding environment, partly due to purely environmental factors, like exposition to pollutions, or anthropological ones, like the type of manual or stressing working activities. The relevant literature has already widely discussed the correlation between the acute and chronic exposition to atmospheric pollutants of different types and the pathogenetic events, such as the atherogenesis, thrombosis, and hypertension, The present study intends to verify this idea on a larger population exposed to different geographical conditions, comparing an agricultural village (Pachino-Siracusa) with an industrialized area (Augusta-Siracusa), both having identical sanitary services of basic importance. On the basis of the specific rates of hospitalizations, we compared the prevalence of cardiovasular pathologies in the resident populations. These studies confirmed the negative influence of the risk factors deriving from the environmental pollutions even on the cardiovascular aging, displaying an increased rate of hospitalization for angina pectoris, myocardial infarction and cardiac arrhytmias in the industrialized population. PMID- 22310209 TI - Studies on health in elderly observation centers (abbreviated from Italian: COSA): a multidimensional evaluation (MDE) of an elderly population frequenting a diurnal center in Catania. AB - The worldwide progressive aging of the population forces us to reconsider the strategies of evaluation the effects of the geriatric "tsunami" on the health politics. The present study on the COSA (abbreviated from the Italian name: "Centro Osservazione Salute Anziani") has the aim to investigate the effects of a new form called Specialistic Geriatric Assistance on the already existing geriatric services in our territory, like UVG (Unita Valutazione Geriatrica), ADI (Assistenza Domiciliare Integrata), MMG (Medici di Medicina Generale). The present preliminary studies were carried out a group of elderly people frequenting the elderly day center "Villa Angela" located in Catania. We enrolled 42 subjects, 29 females and 13 males, in the age-range of 65-89 years (mean=73.6 years). An evaluation protocol was used for the participants, having two parts. The first part was a general one performing an accurate anamnestic examination, while the second part evaluated the cognitive and affective spheres, and the levels of autonomy and autosufficiency. The data obtained show that that the elderly population of the daily center "Villa Angela" in Catania is affected by numerous pathologies and comorbidities, which all increase the total risk of disabilities. The subjects use a high number of medicines (sometimes more than 10), which is not always justified by the pathologies found in them. Considering the functional profiles of the patients, the sanitary services offered to them are appropriate, because almost all of the elderly people were autonomous and autosufficient, having still adequate physical performances. The higher cognitive performance seemed to be reduced in more than 50% of the patients, showing almost always a slight or moderate deterioration. The depressive state measured by the GDS seemed to reach the deflection of joy of life 54.8%, while the established depression was detected in 12%. These results emphasize the importance of the functional psychogeriatric screening, which is able to reveal an early diagnosis of depression in the geriatric ages. For this, and many other motifs, we believe that these preliminary examinations suggest to organize at least one COSA available to our elderly people. PMID- 22310210 TI - Trends associated with Home Care Supporting Clinics (HCSCs) in Japan. AB - AIM: HCSCs were introduced in Japan in April 2006 with the aim of playing a central role in providing end-of-life care at home. However, it is unclear how the HCSCs are operated because statistical data regarding their activities have not been disclosed to the Japanese public. The purpose of this study was to describe the trends associated with the HCSC activity in Tokyo, Japan. METHODS: We submitted an application to the relevant government ministry to disclose the annual activity reports from 2008 to 2010 of the HCSCs located in Tokyo. Reports from each HCSC contained information on the number of patients, the number of deceased patients, their place of death and the number of home visits by physicians and nurses. RESULTS: The number of HCSC activity reports for each year was 1166 (2008), 1209 (2009) and 1246 (2010), while the total number of patients for each year was 67,765 (2008), 67,094 (2009) and 83,486 (2010). Patients who died at home each year under the care of HCSCs was 4431 (2008), 4786 (2009) and 5234 (2010). It is of note that in 2010 about 87% of patients were cared by HCSCs that cared for >50 patients a year and as many as 26.9% of patients who died at home utilized clinics that cared for >50 deceased patients a year. CONCLUSION: The advent of HCSCs caring yearly for >50 patients and deceased patients has led to a shift in the location in which patients receive end-of-life care. PMID- 22310211 TI - Pervaporative separation of bioethanol using a polydimethylsiloxane/polyetherimide composite hollow-fiber membrane. AB - Pervaporation is one of the most promising separation processes for the purification of ethanol. In this study, a composite hollow-fiber membrane with a thin polydimethylsiloxane (PDMS) active layer on a polyetherimide (PEI) macroporous support was used for pervaporative separation of ethanol produced by Saccharomyces cerevisiae from glucose fermentation broth. The pervaporation performance for ethanol/water binary mixtures was strongly dependent on the feed concentration and operating temperature for ethanol concentrations of 1-10%. The composite hollow-fiber membrane was stable over the long-term (about 160 days) with an ethanol permeation flux of 60-62 g/m(2)h and a separation factor of 7-9. In comparison with published results for PDMS composite membranes, the PDMS/PEI hollow-fiber composite membrane had relatively good pervaporation performance with a total flux of 231-252 g/m(2)h. PMID- 22310212 TI - Biocatalyst development by directed evolution. AB - Biocatalysis has emerged as a great addition to traditional chemical processes for production of bulk chemicals and pharmaceuticals. To overcome the limitations of naturally occurring enzymes, directed evolution has become the most important tool for improving critical traits of biocatalysts such as thermostability, activity, selectivity, and tolerance towards organic solvents for industrial applications. Recent advances in mutant library creation and high-throughput screening have greatly facilitated the engineering of novel and improved biocatalysts. This review provides an update of the recent developments in the use of directed evolution to engineer biocatalysts for practical applications. PMID- 22310213 TI - Role of dissolved oxygen availability on lactobionic acid production from whey by Pseudomonas taetrolens. AB - The influence of dissolved oxygen availability on cell growth and lactobionic acid production from whey by Pseudomonas taetrolens has been investigated for the first time. Results from pH-shift bioreactor cultivations have shown that high agitation rate schemes stimulated cell growth, increased pH-shift values and the oxygen uptake rate by cells, whereas lactobionic acid production was negatively affected. Conversely, higher aeration rates than 1.5 Lpm neither stimulated cell growth nor lactobionic acid production (22% lower for an aeration rate of 2 Lpm). Overall insights into bioprocess performance enabled the implementation of 350 rpm as the optimal agitation strategy during cultivation, which increased lactobionic productivity 1.2-fold (0.58-0.7 g/Lh) compared to that achieved at 1000 rpm. Oxygen supply has been shown to be a key bioprocess parameter for enhanced overall efficiency of the system, representing essential information for the implementation of lactobionic acid production at a large scale. PMID- 22310214 TI - Odor abatement in biotrickling filters: effect of the EBRT on methyl mercaptan and hydrophobic VOCs removal. AB - The performance and microbiology of a biotrickling filter (BTF) treating methyl mercaptan, toluene, alpha-pinene and hexane at the mg m(-3) level was studied at empty bed residence times (EBRT) of 50, 30, 11 and 7 s. Removal efficiencies (REs) higher than 95% were observed for MeSH, toluene and alpha-pinene even at 11 s, while hexane REs exceeded 70%. At 7 s, an irreversible damage of the microbial activity due to the accumulation of toxic metabolites resulted in a decrease of REs. The addition of silicone stabilized process performance but only re inoculation allowed achieving a complete removal of MeSH, toluene and alpha pinene, and hexane REs of 80%. The high K(L)a values (ranging from 38 +/- 4 to 90 +/- 11 h(-1)) explained the good BTF performance at such low EBRTs. A high bacterial diversity, along with a vertical distribution of the bacterial communities was observed, the main phyla being Proteobacteria, Actinobacteria, Nitrospira, Chloroflexi and Gemmatimonadertes. PMID- 22310215 TI - Pediatric urolithiasis: causative factors, diagnosis and medical management. AB - Childhood urolithiasis is associated with considerable morbidity and recurrence. Many risk factors--including those metabolic, genetic, anatomic, dietary and environmental in nature--have been identified in children with urinary tract calculi. As pediatric urolithiasis with a metabolic etiology is the most common disease, evaluating the metabolic risk factors in patients is necessary to both effectively treat current stones and prevent recurrence. We discuss causative risk factors of pediatric urolithiasis, as well as the diagnostic and therapeutic approaches. PMID- 22310216 TI - A biomedical engineering approach to mitigate the errors of prostate biopsy. AB - The current protocol for detecting and ruling out prostate cancer involves serum PSA testing followed by sampling of the prostate using a transrectal ultrasonography (TRUS)-guided biopsy. Many specialists have discussed how PSA screening has contributed to underdetection of clinically significant prostate cancer, overdiagnosis of clinically insignificant disease and poor risk stratification; however, little consideration has been given to the role of TRUS guided biopsy in these errors. The performance of TRUS-guided biopsy is constrained by the biomechanical attributes of the sampling strategy, resulting in suboptimal detection efficiency of each core. By using a biomedical engineering approach, a uniform grid sampling strategy could be used to improve the detection efficiency of prostate biopsy. Moreover, the calibration of the sampling can be adjusted by altering the distance between needle deployments. Our model shows that for any given number of needle trajectories, a uniform grid approach will be superior to a divergent, nonuniform strategy for the detection of clinically important disease. This is an important message that should result in a move away from divergent sampling to a uniform grid approach for prostate biopsy. PMID- 22310217 TI - Under the law, FDA must grant different standards for new dietary ingredients and food additives. AB - The FDA's draft Guidance on notifications for new dietary ingredients attempts to narrow the scope of "old" dietary ingredients that do not require notification to FDA and repeats some mistakes from the past by going beyond what is required or permitted by the Food, Drug & Cosmetic Act, as amended by the Dietary Supplements Health and Education Act of 1994. The draft Guidance attempts to apply the notification requirement to new supplements, not just new ingredients, and it expands the working definition of "chemically altered" to include many changes that were not foreseen in the Congressional Record in 1994. Through these misinterpretations, FDA attempts to impose a food additives-like safety standard, and gain de facto premarket approval against the overt wishes of Congress. PMID- 22310218 TI - Trypanosoma cruzi heparin-binding proteins mediate the adherence of epimastigotes to the midgut epithelial cells of Rhodnius prolixus. AB - Heparin-binding proteins (HBPs) have been demonstrated in both infective forms of Trypanosoma cruzi and are involved in the recognition and invasion of mammalian cells. In this study, we evaluated the potential biological function of these proteins during the parasite-vector interaction. HBPs, with molecular masses of 65.8 kDa and 59 kDa, were isolated from epimastigotes by heparin affinity chromatography and identified by biotin-conjugated sulfated glycosaminoglycans (GAGs). Surface plasmon resonance biosensor analysis demonstrated stable receptor ligand binding based on the association and dissociation values. Pre-incubation of epimastigotes with GAGs led to an inhibition of parasite binding to immobilized heparin. Competition assays were performed to evaluate the role of the HBP-GAG interaction in the recognition and adhesion of epimastigotes to midgut epithelial cells of Rhodnius prolixus. Epithelial cells pre-incubated with HBPs yielded a 3.8-fold inhibition in the adhesion of epimastigotes. The pre treatment of epimastigotes with heparin, heparan sulfate and chondroitin sulfate significantly inhibited parasite adhesion to midgut epithelial cells, which was confirmed by scanning electron microscopy. We provide evidence that heparin binding proteins are found on the surface of T. cruzi epimastigotes and demonstrate their key role in the recognition of sulfated GAGs on the surface of midgut epithelial cells of the insect vector. PMID- 22310219 TI - What is the methodological and reporting quality of health related quality of life in chronic heart failure clinical trials? AB - BACKGROUND: Although the number of clinical trials assessing health related quality of life (HRQoL) in chronic heart failure (CHF) has increased exponentially over the last decade, little is known about the quality of reporting. The purpose of this review was to assess the methodological and reporting rigor of HRQoL in RCTs of pharmacological therapy in CHF. METHODS: The electronic data bases, Medline and EMBASE were searched from 1990 to 2009 using the key search terms 'heart failure' combined with 'quality of life', 'pharmacological therapy' and 'randomized controlled trials'. A total of 136 articles were identified and evaluated according to the "Minimum Standard Checklist (MSC) for Evaluating HRQoL Outcomes". RESULTS: According to the MSC criteria, 26 (19.1%) studies were considered 'very limited', 91 (66.9%) were 'limited' and only 19 (14.0%) studies were considered to be of a 'probably robust' in terms of methodological and reporting rigor. In fact, the quality of HRQoL reporting has not improved over time. CONCLUSION: HRQoL is a critical consideration in CHF management, yet reporting is highly variable. There is a need to develop a standardized method for measuring and reporting HRQoL measures in clinical trials to aid in the interpretation and application of findings. PMID- 22310220 TI - Prevalence of esophageal eosinophilia varies by climate zone in the United States. AB - OBJECTIVES: The epidemiology of eosinophilic esophagitis (EoE) is rapidly evolving, and differences in climate could impact the prevalence of EoE. We aimed to examine the association between esophageal eosinophilia and climate zones in the United States. METHODS: This was a cross-sectional study of esophageal biopsies from 2008 to 2010 in a large US pathology database. Cases were patients with esophageal eosinophilia; controls had normal esophageal biopsies. A Koppen Geiger (K-G) climate class was assigned to each patient, and the association between case-control status and the main K-G climate type (tropical, arid, temperate, or cold) was assessed. RESULTS: A total of 233,649 patients were included, 71,948 (30.8%) with normal esophageal biopsies and 9,995 (4.3%) with esophageal eosinophilia. Using the temperate zone as the referent and after multivariable analysis, the odds of esophageal eosinophilia were highest in the cold climate zone (odds ratio (OR)=1.39, 95% confidence interval (CI): 1.34 1.47), compared with the tropical zone (OR=0.87; 95% CI: 0.71-10.8) and the arid zone (OR=1.27; 95% CI: 1.19-1.36). Increased likelihood of EoE was also associated with increasing odds of being in the cold climate zone. Compared with patients with normal esophageal biopsies, patients with dysphagia, a clinical suspicion of EoE, no reflux or Barrett's esophagus, esophageal eosinophilia, and eosinophilic microabscesses had the highest adjusted odds of being in a cold climate zone (OR 2.02; 1.78-2.28). CONCLUSIONS: Esophageal eosinophilia differs significantly between K-G climate zones, with the highest prevalence in the cold and arid zones. Geographical and climate patterns may help identify candidate antigens characteristic to high-prevalence areas to be targeted for future investigation. PMID- 22310221 TI - Long-term follow-up of gut-directed hypnotherapy vs. standard care in children with functional abdominal pain or irritable bowel syndrome. AB - OBJECTIVES: We previously showed that gut-directed hypnotherapy (HT) is highly effective in the treatment of children with functional abdominal pain (FAP) and irritable bowel syndrome (IBS). Aim of this follow-up study was to investigate the long-term effects of HT vs. standard medical treatment plus supportive therapy (SMT). METHODS: All 52 participants of our previous randomized controlled trial (RCT) were invited to complete a standardized abdominal pain diary, on which pain frequency and pain intensity were scored. Furthermore, the Children's Somatization Inventory (CSI) and a general quality of life (QOL) questionnaire were filled out. Clinical remission was defined as > 80% improvement in pain scores compared with baseline. RESULTS: All 27 HT patients and 22 out of 25 SMT patients participated in this study. Two patients of the SMT group were lost to follow-up and one refused to participate. After a mean duration of 4.8 years follow-up (3.4-6.7), HT was still highly superior to conventional therapy with 68 vs. 20% of the patients in remission after treatment (P = 0.005). Pain intensity and pain frequency scores at follow-up were 2.8 and 2.3, respectively, in the HT group compared with 7.3 and 7.1 in the SMT group (P < 0.01). Also, somatization scores were lower in the HT group (15.2 vs. 22.8; P = 0.04). No differences were found in QOL, doctors' visits, and missed days of school or work between the two groups. CONCLUSIONS: The beneficial effects of gut-directed HT are long lasting in children with FAP or IBS with two thirds still in remission almost 5 years after treatment, making it a highly valuable therapeutic option. PMID- 22310222 TI - Management of patients with ulcer bleeding. AB - This guideline presents recommendations for the step-wise management of patients with overt upper gastrointestinal bleeding. Hemodynamic status is first assessed, and resuscitation initiated as needed. Patients are risk-stratified based on features such as hemodynamic status, comorbidities, age, and laboratory tests. Pre-endoscopic erythromycin is considered to increase diagnostic yield at first endoscopy. Pre-endoscopic proton pump inhibitor (PPI) may be considered to decrease the need for endoscopic therapy but does not improve clinical outcomes. Upper endoscopy is generally performed within 24h. The endoscopic features of ulcers direct further management. Patients with active bleeding or non-bleeding visible vessels receive endoscopic therapy (e.g., bipolar electrocoagulation, heater probe, sclerosant, clips) and those with an adherent clot may receive endoscopic therapy; these patients then receive intravenous PPI with a bolus followed by continuous infusion. Patients with flat spots or clean-based ulcers do not require endoscopic therapy or intensive PPI therapy. Recurrent bleeding after endoscopic therapy is treated with a second endoscopic treatment; if bleeding persists or recurs, treatment with surgery or interventional radiology is undertaken. Prevention of recurrent bleeding is based on the etiology of the bleeding ulcer. H. pylori is eradicated and after cure is documented anti-ulcer therapy is generally not given. Nonsteroidal anti-inflammatory drugs (NSAIDs) are stopped; if they must be resumed low-dose COX-2-selective NSAID plus PPI is used. Patients with established cardiovascular disease who require aspirin should start PPI and generally re-institute aspirin soon after bleeding ceases (within 7 days and ideally 1-3 days). Patients with idiopathic ulcers receive long-term anti ulcer therapy. PMID- 22310223 TI - Utilizing prospective sequence analysis of SHH, ZIC2, SIX3 and TGIF in holoprosencephaly probands to describe the parameters limiting the observed frequency of mutant gene*gene interactions. AB - Clinical molecular diagnostic centers routinely screen SHH, ZIC2, SIX3 and TGIF for mutations that can help to explain holoprosencephaly and related brain malformations. Here we report a prospective Sanger sequence analysis of 189 unrelated probands referred to our diagnostic lab for genetic testing. We identified 28 novel unique mutations in this group (15%) and no instances of deleterious mutations in two genes in the same subject. Our result extends that of other diagnostic centers and suggests that among the aggregate 475 prospectively sequenced holoprosencephaly probands there is negligible evidence for direct gene-gene interactions among these tested genes. We model the predictions of the observed mutation frequency in the context of the hypothesis that gene*gene interactions are a prerequisite for forebrain malformations, i.e. the "multiple-hit" hypothesis. We conclude that such a direct interaction would be expected to be rare and that more subtle genetic and environmental interactions are a better explanation for the clinically observed inter- and intra-familial variability. PMID- 22310224 TI - Evolving patient selection and clinical benefit criteria for sapropterin dihydrochloride (Kuvan(r)) treatment of PKU patients. AB - PURPOSE: To understand current patient selection, dosing, and response criteria used for sapropterin dihydrochloride (sapropterin, Kuvan(r)) to treat phenylketonuria (PKU). METHODS: Results of a 2010 survey of twenty-nine academic medical centers are reported to describe practice patterns in comparison to results of a survey done in 2008 and to what is reported in the literature. RESULTS/CONCLUSIONS: In addition to reduction in blood phenylalanine (Phe) levels, clinicians report using broader disease-management approaches when evaluating clinical benefit of sapropterin, including consideration of increased Phe tolerance and behavioral changes. Similar approaches are reported in the literature. PMID- 22310225 TI - Antidepressants differentially modify the extinction of an aversive memory task in female rats. AB - Treatment of major depression, posttraumatic stress disorder and other psychopathologies with antidepressants can be associated with improvement of the cognitive deficits related to these disorders. Although the mechanisms of these effects are not completely elucidated, alterations in the extinction of aversive memories are believed to play a role in these psychopathologies. We have recently verified that female rats present low levels of extinction when submitted to the plus-maze discriminative avoidance task. In the present study, female rats were treated long term with clinically used antidepressants (fluoxetine, nortriptyline or mirtazapine) and subjected to the plus-maze discriminative avoidance task to evaluate learning, memory, extinction and anxiety-related behaviors as well as behavioral despair in the forced swimming test. All groups learned the task and exhibited retrieval. Chronic treatment with fluoxetine (but not with the other antidepressants tested) increased extinction of the discriminative task. In the forced swimming test, the animals treated with fluoxetine and mirtazapine showed decreased immobility duration. In conclusion, fluoxetine potentiated extinction, while both fluoxetine and mirtazapine were effective in ameliorating depressive like behavior in the forced swimming test, suggesting a possible dissociation between the effects on mood and the extinction of aversive memories in female rats. PMID- 22310226 TI - Assessment of cathepsin D and L-like proteinases of poultry red mite, Dermanyssus gallinae (De Geer), as potential vaccine antigens. AB - Vaccination is a feasible strategy for controlling the haematophagous poultry red mite Dermanyssus gallinae. A cDNA library enriched for genes upregulated after feeding was created to identify potential vaccine antigens. From this library, a gene (Dg-CatD-1) encoding a 383 amino acid protein (Dg-CatD-1) with homology to cathepsin D lysosomal aspartyl proteinases was identified as a potential vaccine candidate. A second gene (Dg-CatL-1) encoding a 341 amino acid protein (Dg-CatL 1) with homology to cathepsin L cysteine proteinases was also selected for further study. IgY obtained from naturally infested hens failed to detect Dg-CatD 1 suggesting that it is a concealed antigen. Conversely, Dg-CatL-1 was detected by IgY derived from natural-infestation, indicating that infested hens are exposed to Dg-CatL-1. Mortality rates 120 h after mites had been fed anti-Dg-CatD 1 were significantly higher than those fed control IgY (PF<0.01). In a survival analysis, fitting a proportional hazards model to the time of death of mites, anti-Dg-CatD-1 and anti-Dg-CatL-1 IgY had 4.42 and 2.13 times higher risks of dying compared with controls (PF<0.05). Dg-CatD-1 and L-1 both have potential as vaccine antigens as part of a multi-component vaccine and have the potential to be improved as vaccine antigens using alternative expression systems. PMID- 22310227 TI - 5-Aryl-4-carboxamide-1,3-oxazoles: potent and selective GSK-3 inhibitors. AB - 5-Aryl-4-carboxamide-1,3-oxazoles are a novel, potent and selective series of GSK 3 inhibitors. The optimization of the series to yield compounds with cell activity and brain permeability is described. PMID- 22310228 TI - Novel substituted 9-norbornylpurines and their activities against RNA viruses. AB - We report on the synthesis and the study of the structure-activity relationship of novel 9-norbornyl-6-chloropurine derivatives, which exert selective antiviral activity on the replication of Coxsackievirus B3. In particular, the synthetic approaches towards norbornyl derivatives bearing diverse side chains were studied. The main goal of the study was to determine the influence of the norbornane moiety substitution at positions 5' and 6' on selective antiviral activity with special regard to the liphophilicity profile of the substituent. PMID- 22310229 TI - Structure-activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH. AB - Cryptosporidium parasites are important waterborne pathogens of both humans and animals. The Cryptosporidium parvum and Cryptosporidium hominis genomes indicate that the only route to guanine nucleotides is via inosine 5'-monophosphate dehydrogenase (IMPDH). Thus the inhibition of the parasite IMPDH presents a potential strategy for treating Cryptosporidium infections. A selective benzimidazole-based inhibitor of C. parvum IMPDH (CpIMPDH) was previously identified in a high throughput screen. Here we report a structure-activity relationship study of benzimidazole-based compounds that resulted in potent and selective inhibitors of CpIMPDH. Several compounds display potent antiparasitic activity in vitro. PMID- 22310230 TI - Methoxychalcone inhibitors of androgen receptor translocation and function. AB - Androgen receptor activity drives incurable castrate-resistant prostate cancer. All approved antiandrogens inhibit androgen receptor-driven transcription, and in addition the second-generation antiandrogen MDV3100 inhibits ligand-activated androgen receptor nuclear translocation, via an unknown mechanism. Here, we report methoxychalcones that lock the heat shock protein 90-androgen receptor complex in the cytoplasm in an androgen-non-responsive state, thus demonstrating a novel chemical scaffold for antiandrogen development and a unique mechanism of antiandrogen activity. PMID- 22310231 TI - The association between childhood obesity and tooth eruption. AB - Obesity is a growth-promoting process as evidenced by its effect on the timing of puberty. Although studies are limited, obesity has been shown to affect the timing of tooth eruption. Both the timing and sequence of tooth eruption are important to overall oral health. The purpose of this study was to examine the association between obesity and tooth eruption. Data were combined from three consecutive cycles (2001-2006) of the National Health and Nutrition Examination Survey (NHANES) and analyzed to examine associations between the number of teeth erupted (NET) and obesity status (BMI z-score >95th percentile BMI relative to the Centers for Disease Control and Prevention (CDC) growth reference) among children 5 up to 14 years of age, controlling for potential confounding by age, gender, race, and socioeconomic status (SES). Obesity is significantly associated with having a higher average NET during the mixed dentition period. On average, teeth of obese children erupted earlier than nonobese children with obese children having on average 1.44 more teeth erupted than nonobese children, after adjusting for age, gender, and race/ethnicity (P < 0.0001). SES was not a confounder of the observed associations. Obese children, on average, have significantly more teeth erupted than nonobese children after adjusting for gender, age, and race. These findings may have clinical importance in the area of dental and orthodontic medicine both in terms of risk for dental caries due to extended length of time exposed in the oral cavity and sequencing which may increase the likelihood of malocclusions. PMID- 22310232 TI - Obesity, insulin resistance, and Alzheimer's disease. PMID- 22310233 TI - The impact of insulin resistance and inflammation on the association between sarcopenic obesity and physical functioning. AB - Age associated increases in visceral adiposity and decreases in muscle mass (sarcopenia) have been shown to contribute to disability in late life. Furthermore, there is evidence that obesity-related physiological states, such as insulin resistance and systemic inflammation, may exacerbate physical functioning problems. Both conditions have been shown to prompt hypercatabolism and impair the anabolic effect of muscles, ultimately stimulating protein breakdown and suppressing muscle synthesis. This cross-sectional study investigates whether insulin resistance and inflammation partially account for the associations between decreased physical functioning and sarcopenic obesity. Subjects include 2,287 males and females aged 60 and older without diagnosed diabetes from the National Health and Nutrition Examination Survey (NHANES 1999-2004). Body composition measurements indicating waist circumference and appendicular skeletal muscle mass, measured by dual-energy X-ray absorptiometry (DXA), were used to construct four body composition categories--healthy, sarcopenic nonobese, nonsarcopenic obese, and sarcopenic obese. Physical functioning was measured using self-reports of difficulty performing six activities. The homeostasis model assessment (IR(HOMA)) was used to measure insulin resistance, while inflammatory state was assessed through measurement of serum C-reactive protein (CRP). Modified Poisson regression models were used to examine the association between physical functioning and body composition, and to evaluate whether differences in insulin resistance or inflammation partially explained this relationship. In the analysis, we controlled for possible confounders such as age, education, sex, height, and race/ethnicity. Findings suggest that physical functioning problems are increased in those with sarcopenic obesity, sarcopenic nonobesity and nonsarcopenic obesity. Furthermore, these associations may be influenced by differences in insulin resistance among different body composition phenotypes. PMID- 22310234 TI - Teammates and social influence affect weight loss outcomes in a team-based weight loss competition. AB - Team-based internet interventions are increasing in popularity as a way of promoting weight loss in large numbers of individuals. Given that social networks influence health behavior change, this study investigated the effects of teammates and social influence on individual weight loss during a team-based weight loss competition. Shape Up Rhode Island (SURI) 2009 was a 12-week online program open to adult residents of Rhode Island. Participants joined with a team and competed with other teams on weight loss and/or physical activity. Overweight/obese (OW/OB) individuals (N = 3,330; 76% female; age = 46.1 +/- 10.8; BMI = 31.2 +/- 5.3 kg/m(2)), representing 987 teams, completed the weight loss program. Multilevel modeling was used to examine whether weight loss clustered among teammates and whether percentage of teammates in the weight loss division and reported teammate influence on weight loss were associated with individual weight outcomes. OW/OB completers reported losing 4.2 +/- 3.4% of initial body weight. Weight loss was similar among teammates (intraclass correlation coefficient (ICC) = 0.10, P < 0.001). Moreover, having a greater percentage of teammates in the weight loss division and reporting higher social influence for weight loss were associated with greater percent weight loss (P's <= 0.002). Similarly, achieving a clinically significant (5%) weight loss tended to cluster within teams (ICC = 0.09; P < 0.001) and having more teammates in the weight loss division and higher social influence for weight loss were associated with increased likelihood of achieving a 5% weight loss (odds ratio (OR) = 1.06; OR = 1.20, respectively). These results suggest that teammates affect weight loss outcomes during a team-based intervention. Harnessing and maximizing teammate influence for weight loss may enhance weight outcomes in large-scale team-based programs. PMID- 22310235 TI - What is the role of family in promoting faecal occult blood test screening? Exploring physician, average-risk individual, and family perceptions. AB - BACKGROUND: Although the number of Canadians being screened for colon cancer is rising, only 40% of Canadians aged 50 years or older reported they had engaged in faecal occult blood test (FOBT) screening as recommended. The notion of 'partnerships' that is inclusive of physicians, individuals at average-risk for colorectal cancer, and influential family members is receiving more attention in primary health care literature and policy on promoting health maintenance behaviours. To the best of our knowledge there are no studies that have taken a tripartite approach in describing perspectives of these three key stakeholders on the role of family in promoting adherence to FOBT. The aim of this study was to address the gap in understanding the perspectives of primary care physicians, individuals at average-risk for colorectal cancer, and family on family role in promoting adherence to FOBT screening. METHOD: We employed a qualitative design and conducted semi-structured interviews with 15 physicians, 27 patients at average-risk for colorectal cancer, and 19 family members or friends from urban and rural Manitoba, Canada between October 2008 and March 2010. Interviews were audio-recorded, transcribed verbatim, and analysed using content analysis and constant comparative techniques. RESULTS: While physicians described a clear role for family in managing chronic disease or dealing with acute or serious illness, they identified barriers in working with family to promote FOBT screening: lack of time, privacy and confidentiality concerns, and family dynamics. Conversely, patients and family described instrumental, emotional, informational, and appraisal roles that family play in promoting FOBT outside medical encounters. CONCLUSION: Adherence to colorectal cancer screening is based on supportive 'patient-physician' dialogue that is separate from assistive 'patient-family member' relations. Further research is required to explore social support mechanisms involving family members outside medical encounters that hold promise in boosting self-efficacy, overcoming barriers, and gaining positive reinforcement for individuals at average-risk when making the decision to engage in FOBT. PMID- 22310236 TI - Animal health surveillance: navigation amidst the flotsam of human frailty and fiscal inertia. AB - National veterinary services monitor endemic, emerging and exotic disease situations. They intervene when epidemic tendencies demand. They unravel complex disease situations. They do so as monopolies, in environments of political influence and budgetary restraint. When human, animal health and trade protection dictate, they design import or domestic disease control programs. As much as 80% of program expenditures are on surveillance. Their initiatives are scrutinized by treasuries from which they seek funding, industries from which they seek collaboration and trading partners from whom they seek recognition. In democracies, surveillance and control programs are often the products of a complicated consultative process. It involves individuals who have both a commitment to improving an existing animal health situation and access to the required resources. The generations that designed traditionally risk-averse national surveillance and control programs have given way to a new one which is more epidemiologically informed. Their successors design programs bearing epidemiologically based improvements. The transition, however, has not been overwhelmingly welcomed. Expenditures on surveillance are tolerated out of fear during outbreaks of foreign or re-emergence of indigenous disease. Between epidemics, they decline at the hands of producers' unwillingness and budgetary restraint. Human nature responds to the high cost of surveillance in forms ranging from naivete through to conspiracy. While legislation cannot subdue such human frailty, several other opportunities exist. Education can remove the majority of problems caused by ignorance, leaving the minority that arise intentionally. Technology decreases the high cost of testing which tempts individuals to cut corners. International standards assist National Veterinary Services to overcome domestic resistance. PMID- 22310237 TI - Antitumor activities of quercetin and quercetin-5',8-disulfonate in human colon and breast cancer cell lines. AB - This study is designed to compare the anticancer effects of quercetin and its water-soluble sulfated derivative, quercetin-5',8-disulfonate (QS), in human colon cancer LoVo cells and breast cancer MCF-7 cells. It was found that both quercetin and QS can inhibit the growth of cancer cells in a dose-dependent manner, with the IC(50) values of 40.2 and 28.0 MUM for LoVo cells and 30.8 and 19.9 MUM for MCF-7 cells, respectively, suggesting QS was more effective against the cancer cells than quercetin. Moreover, flow cytometric assay revealed that quercetin and QS could mediate the cell-cycle arrest principally in the S phase after 24h of treatment with the two tumor cells. It was also found that 69.6% of LoVo cells and 90.6% of MCF-7 cells entered the early phase of apoptosis when treated with 100 MUM QS for 48 h. Furthermore, we firstly found the generation of ROS is a critical mediator in QS-induced cell growth inhibition. Taken together, the novel sulfated derivative of quercetin possesses strong antitumor activity via a ROS-dependent apoptosis pathway, and has the excellent potential to be developed into an antitumor precursor compound. PMID- 22310238 TI - Hypoglycemic and beta-cells regenerative effects of Aegle marmelos (L.) Corr. bark extract in streptozotocin-induced diabetic rats. AB - The aim of this study was to examine the antidiabetic potential of Aegle marmelos (L.) Corr. (Rutaceae) bark in a diabetic rat model. Dose dependent effects of methanol extract of Aegle marmelos bark (AM) (200 and 400 mg/kg) on blood glucose, plasma insulin, glycated haemoglobin (HbA1c), total protein, hepatic glycogen, marker enzymes of hepatic function and carbohydrate metabolism were evaluated in (streptozotocin) STZ-induced diabetic rats by oral administration for 30 days. Structural integrity of pancreatic islets was assessed by routine histology while, their functional status was assessed by immunolocalization for insulin. High-performance liquid chromatography (HPLC) study established that AM contained antihyperglycemic constituents, aegelin (1.27% w/w) and lupeol (0.29% w/w). AM at 200 and 400 mg/kg showed significant reduction in blood glucose level by 19.14% and 47.32%, respectively in diabetic rats. AM treatment significantly increased insulin level, and produced similar effects on other biochemical parameters. Histological studies showed the regenerative effect of AM on the beta cells of diabetic rats. Immunohistochemical observations in the extract treated diabetic rats showed increased insulin-immunoreactive beta-cells. These findings suggest that A. marmelos bark extract has the therapeutic potential in STZ induced hyperglycemia; hence it can be used in the treatment of diabetes mellitus. PMID- 22310239 TI - Soil-transmitted helminthiasis: a critical but neglected factor influencing school participation of Aboriginal children in rural Malaysia. AB - Soil-transmitted helminthiasis (STH), among the most common neglected tropical diseases, is a major public health problem in Malaysia with a possible impact on the nutritional status and school participation of rural children. This study was carried out among Aboriginal schoolchildren, living in an endemic area for STH in Malaysia, to determine the possible relationship between intestinal helminthiasis and school absenteeism. We also evaluated whether successful treatment of the infection will affect school attendance among the subjects. Stool analysis revealed that more than 90% of the subjects were infected with at least 1 helminth species, with Ascaris lumbricoides and Trichuris trichiura infections being most prevalent. Infection of moderate-to-heavy worm burdens, low level of fathers' education and anaemia were identified as the significant predictors of high absenteeism among the subjects (P<0.05). Following treatment of the infected children, it was found that school absenteeism was reduced significantly (P<0.01). In conclusion, STH continues to have significant impacts on public health, particularly in rural communities with a negatively significant effect on the school participation of Aboriginal children. A school-based de-worming programme should be introduced and incorporated in the current educational assistance targeted towards the Aboriginal communities, under the auspices of the government. PMID- 22310241 TI - CTCF: from insulators to alternative splicing regulation. PMID- 22310240 TI - Crystal structure and biochemical analyses reveal Beclin 1 as a novel membrane binding protein. AB - The Beclin 1 gene is a haplo-insufficient tumor suppressor and plays an essential role in autophagy. However, the molecular mechanism by which Beclin 1 functions remains largely unknown. Here we report the crystal structure of the evolutionarily conserved domain (ECD) of Beclin 1 at 1.6 A resolution. Beclin 1 ECD exhibits a previously unreported fold, with three structural repeats arranged symmetrically around a central axis. Beclin 1 ECD defines a novel class of membrane-binding domain, with a strong preference for lipid membrane enriched with cardiolipin. The tip of a surface loop in Beclin 1 ECD, comprising three aromatic amino acids, acts as a hydrophobic finger to associate with lipid membrane, consequently resulting in the deformation of membrane and liposomes. Mutation of these aromatic residues rendered Beclin 1 unable to stably associate with lipid membrane in vitro and unable to fully rescue autophagy in Beclin 1 knockdown cells in vivo. These observations form an important framework for deciphering the biological functions of Beclin 1. PMID- 22310242 TI - Defining the expressed breast cancer kinome. PMID- 22310243 TI - Genetic correction of beta-thalassemia patient-specific iPS cells and its use in improving hemoglobin production in irradiated SCID mice. AB - The generation of induced pluripotent stem cells (iPSCs) from differentiated somatic cells by over-expression of several transcription factors has the potential to cure many genetic and degenerative diseases currently recalcitrant to traditional clinical approaches. One such genetic disease is beta-thalassemia major (Cooley's anemia). This disease is caused by either a point mutation or the deletion of several nucleotides in the beta-globin gene, and it threatens the lives of millions of people in China. In the present study, we successfully generated iPSCs from fibroblasts collected from a 2-year-old patient who was diagnosed with a homozygous 41/42 deletion in his beta-globin gene. More importantly, we successfully corrected this genetic mutation in the beta thalassemia iPSCs by homologous recombination. Furthermore, transplantation of the genetically corrected iPSCs-derived hematopoietic progenitors into sub lethally irradiated immune deficient SCID mice showed improved hemoglobin production compared with the uncorrected iPSCs. Moreover, the generation of human beta-globin could be detected in the mice transplanted with corrected iPSCs derived hematopietic progenitors. Our study provides strong evidence that iPSCs generated from a patient with a genetic disease can be corrected by homologous recombination and that the corrected iPSCs have potential clinical uses. PMID- 22310244 TI - Outcome analysis of patients with primary breast cancer initially treated at a certified academic breast unit. AB - INTRODUCTION: Evaluation of oncological outcome and prognostic factors of patients with primary breast cancer treated at a certified academic breast unit. PATIENTS AND METHODS: We prospectively collected data of 3338 patients, diagnosed with primary breast cancer between 01.01.2003 and 31.12.2010 and treated at the Breast Unit Heidelberg, Germany, in order to analyze outcome in clinical practice. We evaluated local control rate (LCR), disease-free survival (DFS), distant disease-free survival (DDFS), observed overall survival (OS) and age adjusted relative overall survival (ROS). In addition, the impact of known prognostic factors on these outcome variables was examined in univariate and multivariate analyses. RESULTS: Of all patients, 368 (11.0%) had carcinoma in situ (CIS) and 197 (5.9%) had bilateral cancers. For the 2970 patients with invasive cancer, of which 49 patients (1.7%) had metastastic disease at time of diagnosis, DFS, LCR, DDFS, OS and ROS at 5 years were 79.8%, 84.7%, 81.2%, 86.3%, and 89.8%, respectively. In multivariate analysis age, pT category, nodal status, hormone receptor status and grading were identified as independent prognostic factors for OS. CONCLUSION: Compared with recent population-based reports from Germany, more favourable patient characteristics and nominally higher survival was found among this large cohort of patients with primary breast cancer treated at a single certified breast unit. PMID- 22310245 TI - Transcranial direct current stimulation treatment protocols: should stimulus intensity be constant or incremental over multiple sessions? AB - Interest in transcranial direct current stimulation (tDCS) as a new tool in neuropsychiatry has led to the need to establish optimal treatment protocols. In an intra-individual randomized cross-over design, 11 healthy volunteers received five tDCS sessions to the left primary motor cortex on consecutive weekdays at a constant or gradually increasing current intensity, in two separate weeks of testing. Cortical excitability was assessed before and after tDCS at each session through peripheral electromyographic recordings of motor-evoked potentials. Both conditions led to significant cumulative increases in cortical excitability across the week but there were no significant differences between the two groups. Motor thresholds decreased significantly from Monday to Friday in both conditions. This study demonstrated that, in the motor cortex, administration of tDCS five times per week whether at a constant intensity or at a gradually increasing intensity was equally effective in increasing cortical excitability. PMID- 22310246 TI - Dual-phase 99mTc sestamibi scintigraphy with neck and thorax SPECT/CT in primary hyperparathyroidism: a single-institution experience. AB - PURPOSE: To assess the diagnostic value of dual-phase (99m)Tc sestamibi scintigraphy with neck and thorax single-photon emission computed tomography/computed tomography (SPECT/CT) in patients with primary hyperparathyroidism, and to analyze the relationships between SPECT/CT data and serum calcium or parathyroid hormone (PTH) concentrations. MATERIALS AND METHODS: (99m)Tc sestamibi scintigraphy was performed in 94 consecutive patients. Images included early and delayed planar neck images and delayed neck and thorax SPECT/CT. Scintigraphy was scored positive or negative. RESULTS: Fifty-nine sestamibi studies (63%) were positive. SPECT/CT demonstrated a single focus in 56 patients, in usual parathyroid sites in 80% of cases and in unusual sites in the remaining 20% (retrotracheal area, 7%; intrathyroidal, 9%; mediastinum, 4%), and double foci in 3. Serum calcium values were higher in patients with a positive scintigraphy than in those with a negative scintigraphy (2.80 vs. 2.66 mmol/L, P = 0.001) with similar figures for serum PTH values (129 vs. 107 pg/mL, P = 0.0649). In patients with a measurable parathyroid adenoma on integrated CT scan (n = 43), the greatest axial diameter of the adenoma was correlated to serum calcium (r = 0.405, P < 0.0071) or PTH concentrations (r = 0.589, P < 0.0001). Fifty-four patients underwent surgery, 45 with a positive, and 9 with a negative preoperative scintigraphy, resulting in a sensitivity of 92% (95% CI: 80-98) and a specificity of 83% (95% CI: 36-100). CONCLUSIONS: Dual-phase (99m)Tc sestamibi scintigraphy with SPECT/CT enables to identify a parathyroid adenoma in about two thirds of patients with primary hyperparathyroidism and allows the surgeon to plan appropriate surgery. The likelihood of scintigraphy to be positive is affected by calcium or PTH concentrations. PMID- 22310247 TI - Diagnostic value of recombinant human thyrotropin-stimulated 123I whole-body scintigraphy in the follow-up of patients with differentiated thyroid cancer. AB - PURPOSE: Published data on recombinant human thyrotropin- (rhTSH-) stimulated iodine-123 (123I) diagnostic whole-body scintigraphy (DxWBS) in differentiated thyroid cancer (DTC) surveillance after initial treatment are limited. We sought to evaluate this modality's diagnostic value in this setting. MATERIALS AND METHODS: We retrospectively compared rhTSH-stimulated 123I DxWBS results with DTC status concurrently determined by stimulated serum thyroglobulin (Tg) measurement, neck ultrasonography, and other imaging studies. Disease was considered present based on stimulated Tg level >=1 MUg/L without interfering Tg autoantibodies with or without positive imaging or biopsy-proven DTC. We also compared scan positivity and disease detection rates of rhTSH-stimulated DxWBS scans obtained with 123I with those acquired with iodine-131 (131I) during the same period. The sample comprised 105 consecutive totally thyroidectomized patients undergoing rhTSH-aided DxWBS with I-123 (n = 67) or with 131I (n = 38) for diagnostic follow-up. rhTSH, 0.9 mg/d, was injected intramuscularly on 2 consecutive days. Oral diagnostic activities of 5 to 10 mCi (185-370 MBq) 123I or 3 mCi (111 MBq) 131I were given on the third day. DxWBS was performed 24 hours (123I) or 48 to 72 hours (131I) later. RESULTS: rhTSH-aided 123I DxWBS scans showed 35.3% sensitivity, 98.0% specificity, 85.7% positive predictive value, and 81.6% negative predictive value. rhTSH-stimulated 123I and 131I DxWBS did not differ in scan positivity (10.4% vs. 13.2%, P = 0.75) or disease detection rates (35.3% vs. 27.8%, P = 1.00). CONCLUSIONS: In DTC, rhTSH-aided 123I DxWBS achieves comparable results in diagnostic follow-up with those of rhTSH-aided 131I DxWBS. Future studies should address the preablation setting and scan activity and timing. PMID- 22310248 TI - Accuracy of central benzodiazepine receptor binding potential/cerebral blood flow SPECT imaging for detecting misery perfusion in patients with unilateral major cerebral artery occlusive diseases: comparison with cerebrovascular reactivity to acetazolamide and cerebral blood flow SPECT imaging. AB - PURPOSE: The aim of the present study was to determine whether central benzodiazepine receptor binding potential (BRBP)/cerebral blood flow (CBF) or a combination of CBF and cerebrovascular reactivity (CVR) to acetazolamide on single-photon emission computed tomography (SPECT) more accurately detects misery perfusion, indicating elevation of absolute value of oxygen extraction fraction (OEF) on positron emission tomography (PET), in patients with unilateral major cerebral artery occlusive diseases. METHODS: In 84 patients, OEF, CBF, CVR to acetazolamide, and BRBP were assessed using 15O-PET and N-isopropyl-p-[123I] iodoamphetamine and [123I]-iomazenil SPECT, respectively. A region of interest was automatically placed in the middle cerebral artery territory using a 3 dimensional stereotactic region of interest template. RESULTS: Sensitivity, specificity, and positive and negative predictive values for the affected side-to contralateral side asymmetry on SPECT-BRBP/CBF to detect the abnormally elevated PET-OEF in the affected hemisphere were 100%, 86.4%, 66.7%, and 100%, respectively. Area under the receiver operating characteristic curve in detecting the abnormally elevated PET-OEF in the affected hemisphere did not differ between analysis of the combination of SPECT-CBF and SPECT-CVR in the affected hemisphere (0.89; 95% confidence interval, 0.80-0.94) and that of the affected side-to contralateral side asymmetry on SPECT-BRBP/CBF (0.93; 95% confidence interval, 0.86-0.97). The combination of the 3 detected abnormally elevated PET-OEF with 97.0% specificity and 90.0% positive predictive value. CONCLUSIONS: The accuracy of central BRBP/CBF asymmetry on SPECT is equivalent to that of the combination of CBF and CVR to acetazolamide on SPECT for detecting misery perfusion in patients with unilateral major cerebral artery occlusive disease. PMID- 22310249 TI - A randomized controlled trial to evaluate the effectiveness of 2 regimens of fixed iodine (131I) doses for Graves disease treatment. AB - AIM: To investigate the effectiveness of 2 fixed iodine (131I) doses for the treatment for Graves hyperthyroidism and their impact on eye disease. METHODS: We prospectively examined 76 patients who received a fixed dose of 370 MBq (group 1) and 52 patients who received 555 MBq 131I (group 2). Patients were followed up for 12 months and considered in remission when they were in a stable euthyroid or hypothyroid state in the absence of antithyroid drugs 12 months after 131I administration. Eight patients with active eye disease received a daily dose of 0.5 mg/kg prednisone per kilogram of body weight at the time of radioiodine therapy for 1 month. RESULTS: The remission rate obtained was similar in groups 1 (73.7%) and 2 (80.8%; P = 0.35). Hypothyroidism was diagnosed in 56.5% of the 370 MBq group and 71.1% of the 555-MBq group patients (P = 0.13). There was no correlation among clinical features, thyroid uptake, antibody levels, serum hormones levels, and outcome. However, logistic regression analysis demonstrated that patients with large thyroid glands had 2.4 times less chance to go into remission (odds ratio; 95% confidence interval = 1.18-4.96). None of the patients developed eye disease during any fixed-dose treatment regimen or worsened their previously diagnosed ophthalmopathy. CONCLUSIONS: Fixed doses of 370 MBq and 555 MBq 131I provided similar remission rates; however, outcome was influenced by the thyroid size. We propose that 370 MBq 131I should be the routine treatment dose for all Graves disease patients, reserving a dose of 555 MBq 131I to palpable large goiters, without any additional concern to eye disease. PMID- 22310250 TI - 68Ga-DOTANOC PET/CT in patients with carcinoma of unknown primary of neuroendocrine origin. AB - OBJECTIVE: To evaluate the role of 68Ga-DOTANOC (68Gallium-labeled [1,4,7,10 tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-octreotide) PET/CT for localization of the primary tumor in patients with carcinoma of unknown primary of neuroendocrine origin. MATERIAL AND METHODS: Twenty patients (median age, 55 years; male 10) with histopathologically proven metastatic neuroendocrine tumor and no localization of primary tumor on conventional imaging were included in the study. PET/CT was done after injection of 132-222 MBq (4-6 mCi) of 68Ga-DOTANOC. Images were evaluated by 2 experienced nuclear medicine physicians both qualitatively as well as quantitatively (maximum standardized uptake value). Histopathology (when available) and/or follow-up imaging with biochemical markers were taken as reference standard. RESULTS: 68Ga-DOTANOC PET/CT localized the primary tumor in 12/20 (60%) patients. Midgut was the most common site of primary tumor (n = 9); duodenum (4), ileum (4), and colon (1). In 1 patient each the primary was localized to the pancreas, stomach, and lung. In these 12 patients, significant correlation was found between maximum standardized uptake value of primary tumor and metastasis (rho = 0.615; P = 0.041). Even in patients in whom no primary tumor was localized, additional sites of metastatic disease were observed when compared with conventional imaging, mostly in lymph nodes and bones. There was a change in management in 3/20 patients (15%), who underwent surgery. In the remaining 17 patients, demonstration of somatostatin receptor expression by PET/CT made them suitable candidate for peptide receptor radionuclide therapy. CONCLUSION: 68Ga-DOTANOC PET/CT seems to be a promising modality for detecting primary tumor in patients with carcinoma of unknown primary of neuroendocrine origin. PMID- 22310251 TI - Different distribution of (62) Cu ATSM and (18)F-FDG in head and neck cancers. AB - PURPOSE: [62Cu]-diacetyl-bis(N4-methlythiosemicarbazone) (Cu-ATSM) was used to delineate hypoxic tissue in head-and-neck cancer, and its distribution was compared with that of 18F-FDG. MATERIALS AND METHODS: Thirty patients with head and-neck cancer underwent Cu-ATSM and FDG PET within a 1 week interval. Accumulation of tracer for each PET image was converted to SUV. After coregisteration of PET images with individual anatomic images, multiple small ROIs were drawn on the tumor mass and applied to both PET images. SUV values were obtained for all ROIs (SUV(roi)), and the SUV(roi) regression lines between Cu ATSM and FDG of each tumor were determined. RESULTS: The SUV mean of Cu-ATSM was lower than that of FDG for both squamous cell carcinoma (SCC) and adenocarcinoma (P < 0.05). In 27 patients with SCC, Cu-ATSM accumulated higher in the peripheral region than in the center of the tumor, and FDG showed the other tendency. Thus, the relationship of the SUV(roi) for Cu-ATSM and FDG showed a negative correlation in SCC. However, 3 adenocarcinoma cases showed similar and homogenous accumulation in the tumor mass with a positive SUV(roi) correlation for the 2 tracers. The regression slope means were -0.12 +/- 0.08 for SCC (n = 27) and 0.28 +/- 0.12 (n = 3) for adenocarcinoma. CONCLUSION: In patients with head-and-neck cancer, intratumoral distribution of Cu-ATSM and FDG showed a negative correlation in SCC and a positive correlation in adenocarcinoma. The 2 tracers represented different pathophysiological microenvironments in different tumors, suggesting that noninvasive hypoxic tissue imaging with Cu-ATSM would be beneficial in the pretreatment evaluation of head-and-neck cancer. PMID- 22310252 TI - Estimation of 123I-IMP arterial blood activity using 123I-IMP acquisition data from the lungs and brain without any blood sampling: validation of its usefulness for quantification of regional cerebral blood flow. AB - OBJECTIVE: The conventional methods for the estimation of regional cerebral blood flow (rCBF) using 123I-labeled N-isopropyl-p-iodoamphetamine (123I IMP) autoradiography (ARG) require continuous or 1-point arterial blood sampling. Patients who need rCBF quantification benefit from the avoidance of arterial puncture. In this study, we attempted to develop a method without any blood sampling to estimate 123I IMP activity in the arterial blood sample at 10 minutes after injection of 123I IMP (Ca10) for the purpose of rCBF quantification. For the evaluation of validity of this method, the mean of rCBFs in various regions of the brain (mean CBF) calculated by 123I IMP ARG method using the estimated Ca10 was compared with that calculated using the Ca10 directly measured with the actual arterial blood sample. Both groups of the mean CBF values were also compared with those measured by O-15 H2O PET ARG method. METHODS: I-123 IMP ARG study was applied to 23 patients, and O-15 H2O PET ARG was applied to 20 patients of them. Dynamic images of the lungs, time series of static images of the brain, and brain SPECT images were acquired after injection of 123I IMP. Arterial blood sampling was done 10 minutes after injection of 123I IMP. Multiple regression analysis was used to estimate Ca10 using 5 parameters from the lung washout counts, time series of brain static counts, and brain SPECT average counts as the explanatory variables and the Ca10 directly measured with the actual arterial blood sample as the objective variable, and the regression equation was calculated. RESULTS: The regression equation was calculated by multiple regression analysis as follows: Estimated Ca10 = (2.09 * 10-2 . LW3) - (2.29 * 10 4 . Cb5) - (9.87 * 10-3 . Cbpre-SPECT) + (1.06 . CbSPECTav) + (1.03 * 10-2 . Cbpost-SPECT) + 165 (counts/s/g), where LW3: lung washout count at 3 minutes after injection, Cb5: brain count at 5 minutes, Cb pre-SPECT: brain count before SPECT, Cb SPECT av: average brain count during SPECT, and Cb post-SPECT: brain count after SPECT. The estimated Ca10 values closely correlated with the directly measured Ca10 values (r = 0.907, P < 0.01). The mean CBF values (mL/min/100 g) calculated by 123I IMP ARG method using the estimated Ca10 also closely correlated with those calculated using the directly measured Ca10 (r = 0.818, P < 0.01). The mean CBF values calculated by the 123I IMP ARG method using either the directly measured or the estimated Ca10 significantly correlated (r = 0.698 and 0.590, respectively; P < 0.01) with those measured by O-15 H2O PET ARG method. CONCLUSIONS: The 123I IMP arterial blood activity can be estimated reliably without any blood sampling using the 123I IMP acquisition data from the lungs and brain. This method can serve for a convenient and noninvasive rCBF quantification technique instead of the conventional methods requiring arterial blood sampling. PMID- 22310253 TI - Utility of additional delayed post-therapeutic 131I whole-body scanning in patients with thyroid cancer. AB - OBJECTIVE: The purpose of this study is to compare early (3 days after administration) and delayed (7-9 days after administration) post-therapeutic 131I scanning for detecting metastatic lesions from differentiated thyroid carcinoma. METHODS: This study included 24 patients (10 men and 14 women) with differentiated thyroid carcinoma who underwent early and delayed whole-body scanning after 131I treatment. The early and delayed scan images were visually analyzed, and the region-to-whole-body ratio (RBR) and its variation from the early to delayed scanning (RBR variation) were calculated. RESULTS: In the visual analysis, lung metastases in 2 patients and 1 bone metastasis could not be detected on early scanning but were classified as moderate uptake on delayed scanning. The abdomen showed definite uptake on early scanning but was washed out on delayed scanning. The RBR variation of the lung and bone metastases was significantly higher than those of the abdomen and thyroid remnants. This suggests that the distribution of 131I was more quickly washed out of the abdomen and thyroid remnants than from the metastatic lesions. CONCLUSIONS: Delayed scanning showed a higher detection rate of lung and bone metastases than early scanning because of the washout of the physiological distributions. Additional delayed scanning is recommended, especially for high-risk patients with intensive physiological distribution on early scanning. PMID- 22310254 TI - Voxel-based quantitative analysis of brain images from 18F-FDG PET with a block matching algorithm for spatial normalization. AB - OBJECTIVE: Statistical Parametric Mapping (SPM) is widely used for the quantitative analysis of brain images from 18F fluorodeoxyglucose positron emission tomography (FDG PET). SPM requires an initial step of spatial normalization to align all images to a standard anatomic model (the template), but this may lead to image distortion and artifacts, especially in cases of marked brain abnormalities. This study aimed at assessing a block-matching (BM) normalization algorithm, where most transformations are not directly computed on the overall brain volume but through small blocks, a principle that is likely to minimize artifacts. METHODS: Large and/or small hypometabolic areas were artificially simulated in initially normal FDG PET images to compare the results provided by statistical tests computed after either SPM or BM normalization. RESULTS: Results were enhanced by BM, compared with SPM, with regard to (i) errors in the estimation of large defects volumes (about 2-fold lower) because of a lower image distortion, and (ii) rates of false-positive foci when numerous or extended abnormalities were simulated. These observations were strengthened by analyses of FDG PET examinations from epileptic patients. CONCLUSIONS: Results obtained with the BM normalization of brain FDG PET appear more precise and robust than with SPM normalization, especially in cases of numerous or extended abnormalities. PMID- 22310255 TI - Communicating in organizations, part I: general principles of high-stakes discussions. AB - Communication skills are important for all members in an organization, and especially the leaders. Leaders must be proficient in many different types of conversations, such as one-on-one dialogue, group meetings, speeches, electronic exchanges of messages, newsletters, question and answer sessions with various stakeholders and the media, and so forth. This series of articles will review some important aspects of communication within an organization. PMID- 22310256 TI - A patient with a preexisting (nontoxic, nonautonomous) thyroid nodule and concurrent thyroiditis mimicking a toxic solitary autonomous thyroid nodule on 99mTcO4 scintigraphy. PMID- 22310257 TI - Rare breast and adrenal gland metastases from small-cell neuroendocrine carcinoma of uterine cervix. PMID- 22310258 TI - FDG PET/CT in diagnosing and staging cutaneous eccrine adenocarcinoma. PMID- 22310259 TI - Graves disease mimicking solitary autonomous nodule at scintigraphy. PMID- 22310260 TI - Radionuclide imaging with SPECT/CT in suspected cerebrospinal fluid leakage. PMID- 22310261 TI - 18F-FDG PET findings of a parathyroid cancer with cortical skeletal demineralization. PMID- 22310262 TI - Adrenocorticotropic hormone-secreting tumor in the pancreas identified by PET/CT. PMID- 22310263 TI - 67Ga uptake after cosmetic augmentation with silicone in HIV-infected patient with unexplained hypercalcemia: utility of SPECT/CT. PMID- 22310264 TI - Contribution of SPECT/CT to the diagnosis of a pancreatic tail tumor in a case of multiple endocrine neoplasia type 1. PMID- 22310265 TI - Incidental diagnosis of struma ovarii detected with 99mTc SPECT/CT. PMID- 22310266 TI - False-positive bone metastases on PET/CT secondary to sarcoidosis in a patient with rectal cancer. PMID- 22310267 TI - The use of 18F-FDG PET/CT in Cowden syndrome to differentiate multifocal gastric carcinoma from extensive benign gastric polyposis. PMID- 22310268 TI - Current readings in nuclear medicine. PMID- 22310269 TI - Correlation of clinicopathological features and expression of molecular markers with prognosis after 131I treatment of differentiated thyroid carcinoma. AB - PURPOSE: The aim of this study was to identify molecular markers associated with differentiated thyroid carcinoma (DTC) patients and to determine whether there was a correlation between clinicopathological features or molecular markers and the outcome of radioiodine therapy. PATIENTS AND METHODS: We retrospectively reviewed the records of 68 patients with papillary thyroid carcinoma (PTC) and 6 patients with follicular thyroid carcinoma (FTC), who underwent iodine treatment. All patients were divided into a cured group (no evidence for disease) and a noncured group (presence of residual or recurrent disease). Immunohistochemical analysis of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER)-2 (C-erbB-2), ephrin receptor (EphA-2), and sodium iodide symporter (NIS) was performed in all DTC specimens (68 PTCs, 6 FTCs) and in 14 follicular adenoma specimens. RESULTS: Male patients and patients with lymph node and distant metastases had poorer prognosis. Overexpression of ER, PR, HER-2, EphA-2, and NIS was observed in 50.0% (37), 73.0% (54), 52.7% (39), 67.5% (50), and 70.3% (52) of DTC patients, respectively, and was significantly higher than in follicular adenoma patients (0%, 7.14%, 14.29%, 35.7%, and 35.7%, respectively). However, in patients with DTC, no significant difference in the expression of any marker was seen between the cured group and noncured group. CONCLUSIONS: Male gender, and lymph node and distant metastases were found to be poor prognostic factors for patients with DTC. Higher expressions of ER, PR, HER 2, EphA-2, and NIS were associated with DTC, but were not correlated with the effectiveness of radioiodine treatment. PMID- 22310270 TI - Effects of rosiglitazone on radioiodine negative and progressive differentiated thyroid carcinoma as assessed by 124I PET/CT imaging. AB - AIM: The aim of this study was to evaluate the redifferentiative and antiproliferative effects of rosiglitazone in patients with progressive differentiated thyroid cancer (DTC) without or with negligible overall radioiodine uptake. MATERIALS AND METHODS: A total of 9 patients with progressive DTC with either no or only negligible radioiodine accumulation were enrolled in this study. Oral rosiglitazone treatment was applied for 6 months (4 mg per day for 2 weeks followed by 8 mg per day). The compatibility of the medication was initially checked twice weekly and then weekly by laboratory tests and clinical evaluation of side effects. The assessments of alterations in the doses absorbed by the tumor and in lesion sizes over the course of rosiglitazone treatment were performed using serial 124I positron emission tomography and computed tomography imaging. The assessment time points were before enrollment and 3 and 6 months posttreatment initiation. RESULTS: Lesion dosimetry indicated that 5 of 9 patients had an improved lesion absorbed dose per administered activity (LDpA), yielding in radioiodine therapy treatment in 4 patients. One third of the patients (3/9) were unchanged with regard to LDpA, and 1 of 9 had deteriorated LDpA. Volumetric analyses revealed that lesion sizes were regredient in 3 of 9 patients, stable in 4 of 9, and was progressive in 1 of 9. The medication was well-tolerated, and no patient developed clinically important toxicity associated with rosiglitazone treatment. In 2 of 9 of the patients, the medication was terminated after 3 months as a precaution due to progressive heart disease in one patient and bone fracture within a known osteolytic bone lesion in another patient. It is not clear that these complications were caused by rosiglitazone. CONCLUSION: Rosiglitazone appears to be suitable as off-label therapy in radioiodine-negative and progressive DTC that lacks therapy alternatives. In Europe, rosiglitazone was removed for label use because of reported side effects during diabetes treatment. Further investigations of other available glitazone compounds are necessary. PMID- 22310271 TI - 111In OctreoScan SPECT-MRI fusion for the detection of a pancreatic insulinoma. PMID- 22310272 TI - Hyperprolactinemia-related 131I uptake in nonlactating breasts. PMID- 22310273 TI - Abnormal 131I uptake in a benign serous ovarian cystadenoma mimicking bladder physiological uptake. PMID- 22310274 TI - 18F-FDG PET/CT imaging for mixed germ cell tumor in the pineal region. PMID- 22310275 TI - False-positive 131I uptake in fixed prosthetic denture. PMID- 22310276 TI - Evaluation of a column classification method using the separation of alfuzosin from its related substances. AB - The popularity and commercial availability of reversed-phase liquid chromatographic (RP-LC) stationary phases cause analysts to be often confronted with the problem of column selection. For this reason, general test methods to characterize RP-LC columns have been extensively studied since the 1970s. This paper focuses on correlating the column classification based on a method developed at the Katholieke Universiteit Leuven (KUL method) with the selectivity obtained for a real separation. The analysis of alfuzosin hydrochloride and related compounds was carried out according to the method prescribed in the European Pharmacopoeia (Ph. Eur.) monograph. This separation was performed on 36 new RP-LC stationary phases which had been previously characterized chromatographically. For deeper comparative analysis of KUL classification of the stationary RP-LC brands and their column performance in pharmaceutical practice two chemometric tools, such as principal component analysis (PCA) and cluster analysis (CA), have been used. It was shown that stationary phase classes closely related by KUL method gave comparable separation for alfuzosin and related compounds. Therefore, the column ranking system based on the evaluation of F values can be considered as a helpful tool in the selection of a suitable column for pharmaceutical analyses. PMID- 22310277 TI - Unexpected retention behavior of supercritical fluid chromatography at the low density near critical region of carbon dioxide. AB - The retention factors of octylbenzene, octadecene, anthracene, and pyrene eluted from columns packed with neat silica and C(18)-bonded silica by pure carbon dioxide near its critical region increase with increasing temperature along low density isopycnic lines. This behavior is markedly different from the one observed in nearby regions of the pressure-temperature diagram of CO(2), where the retention factors of these compounds decrease with increasing temperature along high-density isopycnic lines. Several possible reasons that could explain this reversal in the behavior of the retention factors are discussed. The most plausible is related to the formation of multilayer adsorption of CO(2) on the stationary phases in a density range slightly lower than the critical density. PMID- 22310278 TI - Is pulsed electric field still effective for RNA separation in capillary electrophoresis? AB - Pulsed field capillary electrophoresis (PFCE) is a predominant technique to cope with difficulties in resolving large DNA strands, yet it is still unclear whether pulsed electric field is effective for the separation of higher mass RNA. In this paper we focused on the role of pulsed electric field in large RNA fragments analysis by comparing RNA separation performance in PFCE with that in constant field CE. Separation performance in terms of migration mobility, plate numbers, resolution, and selectivity has been tested for the analysis of RNA from 0.1 to 10.0 kilo nucleotide (knt) under different electrophoretic conditions. Denaturation, important to obtain uniform and identifiable peaks, was accomplished by heating the sample in 4.0M urea prior to analysis and the presence of 4.0M urea in the electrophoresis buffer. Results demonstrate that unlike DNA in PFCE, the pulsed electric field mainly affects the separation performance of RNA between 0.4 and 2.0 knt. The migration mobility of long RNA fragments is not a strong function of modulation depth and pulsed frequency. Moreover, the logarithm of RNA mobility is almost inversely proportional to the logarithm of molecule size up to 6.0 knt with correlation coefficient higher than 0.99 in all the polymer concentrations measured here. Resonance frequency of RNA in PFCE was also observed. While these initial experiments show no distinct advantages of using PFCE for RNA separation, they do take further step toward characterizing the migration behavior of RNA under pulsed field conditions. PMID- 22310279 TI - Targeting tumor cell metabolism with statins. AB - The mevalonate pathway is a core biochemical process, crucial for the generation of cholesterol and other key metabolic end products. The rate-limiting enzyme of the mevalonate pathway, hydroxymethylglutaryl coenzyme A reductase (HMGCR), is safely and effectively targeted by the statin family of inhibitors to treat hypercholesterolemia. The anticancer activity of statins has also been widely reported, yet the tumor-selective mechanisms that mediate these antiproliferative effects remain largely unclear. The importance of altered metabolism in the context of tumorigenesis has received renewed attention as metabolic changes entwined with the molecular hallmarks of cancer have been elucidated. Although several metabolic pathways have been linked to cancer progression and etiology, it was only recently that HMGCR and the mevalonate pathway were also shown to have a distinct role in cellular transformation. In this review, we chart the historical progression of statins from cholesterol-lowering blockbusters to anticancer agents with imminent potential, and further discuss an emerging role for HMGCR and the mevalonate pathway in the metabolic reprogramming of cancer. PMID- 22310280 TI - Role of the integrin-linked kinase (ILK)/Rictor complex in TGFbeta-1-induced epithelial-mesenchymal transition (EMT). AB - Epithelial-to-mesenchymal transition (EMT) causes fibrosis, cancer progression and metastasis. Integrin-linked kinase (ILK) is a focal adhesion adaptor and a serine/threonine protein kinase that regulates cell proliferation, survival and EMT. Elucidating the molecular mechanisms necessary for development and progression of human malignancies is critical to predict the most appropriate targets for cancer therapy. Here, we used transforming growth factor beta-1 (TGFbeta-1) to promote EMT and migration in mammary epithelial cells. We demonstrate a requirement of ILK activity for TGFbeta-1-mediated EMT in mammary epithelial cells. In addition to nuclear translocation of Snail and Slug, TGFbeta 1 treatment also induced expression of the mammalian target of rapamycin complex 2 component Rictor and its phosphorylation on Thr1135. Interestingly, TGFbeta-1 treatment also induced an interaction between ILK and Rictor. All of these TGFbeta-1-induced processes were significantly suppressed by inhibiting ILK activity or by disrupting the ILK/Rictor complex using small-interfering RNA mediated knockdown. Furthermore, we identified ILK/Rictor complex formation in cancer but not in normal cell types, and this was accompanied by ILK-dependent phosphorylation of Rictor on residue Thr1135. Inhibition of ILK partially reversed the basal mesenchymal phenotype of MDA-MB-231 cells and prevented EMT in MCF10A cells after TGFbeta-1 treatment. These data demonstrate a requirement for ILK function in TGFbeta-1-induced EMT in mammary epithelial cells and identify the ILK/Rictor complex as a potential molecular target for preventing/reversing EMT. PMID- 22310281 TI - BAG3 controls angiogenesis through regulation of ERK phosphorylation. AB - BAG3 is a co-chaperone of the heat shock protein (Hsp) 70, is expressed in many cell types upon cell stress, however, its expression is constitutive in many tumours. We and others have previously shown that in neoplastic cells BAG3 exerts an anti-apoptotic function thus favoring tumour progression. As a consequence we have proposed BAG3 as a target of antineoplastic therapies. Here we identify a novel role for BAG3 in regulation of neo-angiogenesis and show that its downregulation results in reduced angiogenesis therefore expanding the role of BAG3 as a therapeutical target. In brief we show that BAG3 is expressed in endothelial cells and is essential for the interaction between ERK and its phosphatase DUSP6, as a consequence its removal results in reduced binding of DUSP6 to ERK and sustained ERK phosphorylation that in turn determines increased levels of p21 and p15 and cell-cycle arrest in the G1 phase. PMID- 22310282 TI - EphB2 receptor controls proliferation/migration dichotomy of glioblastoma by interacting with focal adhesion kinase. AB - Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumors in adults. Uncontrolled proliferation and abnormal cell migration are two prominent spatially and temporally disassociated characteristics of GBMs. In this study, we investigated the role of the receptor tyrosine kinase EphB2 in controlling the proliferation/migration dichotomy of GBM. We studied EphB2 gain of function and loss of function in glioblastoma-derived stem-like neurospheres, whose in vivo growth pattern closely replicates human GBM. EphB2 expression stimulated GBM neurosphere cell migration and invasion, and inhibited neurosphere cell proliferation in vitro. In parallel, EphB2 silencing increased tumor cell proliferation and decreased tumor cell migration. EphB2 was found to increase tumor cell invasion in vivo using an internally controlled dual-fluorescent xenograft model. Xenografts derived from EphB2-overexpressing GBM neurospheres also showed decreased cellular proliferation. The non-receptor tyrosine kinase focal adhesion kinase (FAK) was found to be co-associated with and highly activated by EphB2 expression, and FAK activation facilitated focal adhesion formation, cytoskeleton structure change and cell migration in EphB2-expressing GBM neurosphere cells. Taken together, our findings indicate that EphB2 has pro invasive and anti-proliferative actions in GBM stem-like neurospheres mediated, in part, by interactions between EphB2 receptors and FAK. These novel findings suggest that tumor cell invasion can be therapeutically targeted by inhibiting EphB2 signaling, and that optimal antitumor responses to EphB2 targeting may require concurrent use of anti-proliferative agents. PMID- 22310284 TI - New frontiers in promoting tumour cell death: targeting apoptosis, necroptosis and autophagy. AB - Cancer is a multifaceted disease comprising a combination of genetic, metabolic and signalling aberrations, which severely disrupt the normal homeostasis of cell growth and death. Many oncogenic events while promoting tumour development also increase the sensitivity of cells to cell death stimuli including chemotherapeutic drugs. As a result, tumour cells often acquire the ability to evade death by inactivating cell death pathways that normally function to eliminate damaged and harmful cells. The impairment of cell death function is also often the reason for the development of chemotherapeutic resistance encountered during treatment. It is therefore necessary to achieve a comprehensive understanding of existing cell death pathways and the relevant regulatory components involved, with the intention of identifying new strategies to kill cancer cells. This review provides an insightful overview of the common forms of cell death signalling pathways, the interactions between these pathways and the ways in which these pathways are deregulated in cancer. We also discuss the emerging therapies targeted at activating or restoring cell death pathways to induce tumour cell death, which are currently being tested in clinical trials. PMID- 22310283 TI - Dynamic interaction between TAL1 oncoprotein and LSD1 regulates TAL1 function in hematopoiesis and leukemogenesis. AB - TAL1/SCL is a hematopoietic-specific oncogene and its activity is regulated by associated transcriptional co-activators and corepressors. Dysregulation of TAL1 activity has been associated with T-cell leukemogenesis. However, it remains unclear how the interactions between TAL1 and corepressors versus co-activators are properly regulated. Here, we reported that protein kinase A (PKA)-mediated phosphorylation regulates TAL1 interaction with the lysine-specific demethylase (LSD1) that removes methyl group from methylated Lys 4 on histone H3 tails. Phosphorylation of serine 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction leading to promoter H3K4 hypermethylation and activation of target genes that have been suppressed in normal and malignant hematopoiesis. Knockdown of TAL1 or LSD1 led to a derepression of the TAL1 target genes in T-cell acute lymphoblast leukemia (T-ALL) Jurkat cells, which is accompanied by elevating promoter H3K4 methylation. Similarly, treatment of PKA activator forskolin resulted in derepression of target genes by reducing its interaction with LSD1 while PKA inhibitor H89 represses them by suppressing H3K4 methylation levels. Consistent with the dual roles of TAL1 in transcription, TAL1-associated LSD1 is decreased while recruitment of hSET1 is increased at the TAL1 targets during erythroid differentiation. This process is accompanied by a dramatic increase in H3K4 methylation. Thus, our data revealed a novel interplay between PKA phosphorylation and TAL1-mediated epigenetic regulation that regulates hematopoietic transcription and differentiation programs during hematopoiesis and leukemogenesis. PMID- 22310285 TI - Foxo3a transcription factor is a negative regulator of Skp2 and Skp2 SCF complex. AB - Skp2 (S-phase kinase-associated protein-2) SCF complex displays E3 ligase activity and oncogenic activity by regulating protein ubiquitination and degradation, in turn regulating cell cycle entry, senescence and tumorigenesis. The maintenance of the integrity of Skp2 SCF complex is critical for its E3 ligase activity. The Skp2 F-box protein is a rate-limiting step and key factor in this complex, which binds to its protein substrates and triggers ubiquitination and degradation of its substrates. Skp2 is found to be overexpressed in numerous human cancers, which has an important role in tumorigenesis. The molecular mechanism by which the function of Skp2 and Skp2 SCF complex is regulated remains largely unknown. Here we show that Foxo3a transcription factor is a novel and negative regulator of Skp2 SCF complex. Foxo3a is found to be a transcriptional repressor of Skp2 gene expression by directly binding to the Skp2 promoter, thereby inhibiting Skp2 protein expression. Surprisingly, we found for the first time that Foxo3a also displays a transcription-independent activity by directly interacting with Skp2 and disrupting Skp2 SCF complex formation, in turn inhibiting Skp2 SCF E3 ligase activity and promoting p27 stability. Finally, we show that the oncogenic activity of Skp2 is repressed by Foxo3a overexpression. Our results not only reveal novel insights into how Skp2 SCF complex is regulated, but also establish a new role for Foxo3a in tumor suppression through a transcription-dependent and independent manner. PMID- 22310286 TI - Switching from aerobic glycolysis to oxidative phosphorylation modulates the sensitivity of mantle cell lymphoma cells to TRAIL. AB - TRAIL (TNF (tumour necrosis factor)-related apoptosis-inducing ligand) a putative anti-cancer cytokine induces apoptosis through DISC (death-inducing signalling complex)-mediated activation of caspase-8 and/or cleavage of Bid. TRAIL is relatively specific for tumour cells but primary chronic lymphocytic leukaemia and mantle cell lymphoma (MCL) cells are resistant. Herein, we show that cellular metabolism influences cell death and that MCL cells (Z138 cell line) can survive/proliferate in glucose-free media by switching from aerobic glycolysis to 'coupled' oxidative phosphorylation. Extracellular flux analysis and mitochondrial inhibitors reveal that in the absence of glycolysis, Z138 cells have enhanced respiratory capacity coupled to ATP synthesis, similar to 'classical' state 3 mitochondria. Conversely, 2-deoxyglucose (2DG) blocked glycolysis and partially inhibited glycolytic-dependent oxidative phosphorylation, resulting in a 50% reduction in cellular ATP levels. Also, 2DG sensitised Z138 cells to TRAIL and induced a marked decrease in caspase-8, -3, cFLIP(S), Bid and Mcl-1 expression but Bak remained unchanged, altering the Mcl 1/Bak ratio, facilitating cytochrome c release and cell death. Conversely, under glucose-free conditions, Z138 cells were less sensitive to TRAIL with reduced TRAIL-R1/R2 surface receptor expression and impaired DISC formation. Anti apoptotic proteins Bcl-2 and XIAP were up-regulated while pro-apoptotic BAX was down-regulated. Additionally, mitochondria had higher levels of cytochrome c and ultrastucturally exhibited a condensed configuration with enhanced intracristal spaces. Thus, metabolic switching was accompanied by mitochondrial proteome and ultrastructural remodelling enabling enhanced respiration activity. Cytochrome c release was decreased in glucose-free cells, suggesting that either pore formation was inhibited or that cytochrome c was more tightly bound. Glucose-free Z138 cells were also resistant to intrinsic cell death stimuli (ABT-737 and ionising radiation). In summary, in MCL cells, the anti-glycolytic effects of 2DG and glucose restriction produced opposite effects on TRAIL-induced cell death, demonstrating that mitochondrial metabolism directly modulates sensitivity of tumour cells to apoptosis. PMID- 22310287 TI - Combination of MEK and SRC inhibition suppresses melanoma cell growth and invasion. AB - The RAS-RAF-MEK-ERK pathway is deregulated in over 90% of malignant melanomas, and targeting MEK as a central kinase of this pathway is currently tested in clinical trials. However, dose-limiting side effects are observed, and MEK inhibitors that sufficiently reduce ERK activation in patients show a low clinical response. Apart from dose limitations, a reason for the low response to MEK targeting drugs is thought to be the upregulation of counteracting signalling cascades as a direct response to MEK inhibition. Therefore, understanding the biology of melanoma cells and the effects of MEK inhibition on these cells will help to identify new combinatorial approaches that are more potent and allow for lower concentrations of the drug being used. We have discovered that in melanoma cells MEK inhibition by selumetinib (AZD6244, ARRY-142886) or PD184352, while efficiently suppressing proliferation, stimulates increased invasiveness. Inhibition of MEK suppresses actin-cortex contraction and increases integrin mediated adhesion. Most importantly, and surprisingly, MEK inhibition results in a significant increase in matrix metalloproteases (MMP)-2 and membrane-type 1-MMP expression. All together, MEK inhibition in melanoma cells induces a 'mesenchymal' phenotype that is characterised by protease-driven invasion. This mode of invasion is dependent on integrin-mediated adhesion, and because SRC kinases are the main regulators of this process, the SRC kinase inhibitor, saracatinib (AZD0530), completely abolished the MEK inhibitor-induced invasion. Moreover, the combination of saracatinib and selumetinib effectively suppressed the growth and invasion of melanoma cells in a 3D environment, suggesting that combined inhibition of MEK and SRC is a promising approach to improve the efficacy of targeting the ERK/MAP kinase pathway in melanoma. PMID- 22310288 TI - DNA demethylation in normal colon tissue predicts predisposition to multiple cancers. AB - Some colon cancer (CC) patients present synchronous cancers at diagnosis and others develop metachronous neoplasms, but the risk factors are unclear for non hereditary CC. We showed previously that global DNA demethylation increased with aging and correlated with genomic damage in CC, and we show now that preferentially associates to CCs with wild-type p53. This study aimed to elucidate the extent of DNA hypomethylation in patients with single and multiple CC, its relationship with aging, and its potential as predictive tool. We compared by real-time methylation-specific PCR the relative demethylation level (RDL) of long interspersed nucleotide element-1 (LINE-1) sequences in matched cancer tissues and non-cancerous colonic mucosa (NCM) from patients with single and multiple right-sided CCs. Although no RDL difference was found in NCM from single CC patients and healthy volunteers (P=0.5), there was more demethylation (higher RDL) in NCM from synchronous cancer patients (P=1.1 * 10(-5)) multiple CCs also were more demethylated than single CCs (P=0.0014). High NCM demethylation was predictive for metachronous neoplasms (P=0.003). In multivariate logistic regression analyses RDL was the only independent predictor for metachronous (P=0.02) and multiple (P=4.9 * 10(-5)) tumors. The higher LINE-1 demethylation in NCM from patients with multiple (synchronous and metachronous) tumors (P=9.6 * 10(-7)) was also very significant in patients with tumors without (P=3.8 * 10(-6)), but not with (P=0.16) microsatellite instability. NCM demethylation increased with aging in patients with single tumors, but decreased in those with multiple tumors. Moreover, the demethylation difference between patients with single vs multiple tumors appeared higher in younger (P=3.6 * 10( 4)) than in older (P=0.0016) patients. These results predict that LINE-1 hypomethylation in NCM can be used as an epigenetic predictive biomarker for multiple CC risk. The stronger association of demethylation in NCM with multiple CC risk from younger patients also suggests an inherited predisposition for the apparent field cancerization effect of somatic demethylation. PMID- 22310289 TI - Critical role of the death receptor pathway in the antitumoral effects induced by hispanolone derivatives. AB - Labdane diterpenoids have a broad spectrum of biological activities including antibacterial, antiviral and anti-inflammatory properties. However, little is known about their possible role in the apoptotic cell death machinery. Here, we report that hispanolone derivatives, a group of labdane diterpenoids, induce apoptosis in different tumor cell lines by activating caspase-8 with subsequent participation of mitochondrial signaling. Activation of caspase-8 by hispanolone derivatives was followed by a decrease in mitochondrial membrane potential, the release of apoptotic factors from mitochondria to the cytosol, and activation of caspases-9 and 3. Hispanolone derivatives also led to a time-dependent cleavage of Bid. Inhibition of caspase-8 abrogated these processes, suggesting that the death receptor pathway has a critical role in the apoptotic events induced by hispanolone derivatives. In addition, silencing death receptors with small interfering RNA s or pretreating cells with neutralizing antibodies to Fas ligand, tumor necrosis factor receptor 1 (TNF-R1), and TNF-alpha receptor 2 (TRAIL) inhibited diterpenoid-induced apoptosis, revealing it to be dependent on these death receptors. Interestingly, hispanolone derivatives had no effect on non-tumor cells. Consistently, in vivo bioluminescence imaging corroborates this antineoplasic effect, as hispanolone derivatives significantly decrease cancer growth in tumor xenograft assays. These data demostrate the antitumoral effects of hispanolone derivatives and provide relevant preclinical validation for the use of these compounds as potent therapeutic agents in cancer treatment. PMID- 22310290 TI - CBL enhances breast tumor formation by inhibiting tumor suppressive activity of TGF-beta signaling. AB - Casitas B-lineage lymphoma (CBL) protein family functions as multifunctional adaptor proteins and E3 ubiquitin ligases that are implicated as regulators of signaling in various cell types. Recent discovery revealed mutations of proto oncogenic CBL in the linker region and RING finger domain in human acute myeloid neoplasm, and these transforming mutations induced carcinogenesis. However, the adaptor function of CBL mediated signaling pathway during tumorigenesis has not been well characterized. Here, we show that CBL is highly expressed in breast cancer cells and significantly inhibits transforming growth factor-beta (TGF beta) tumor suppressive activity. Knockdown of CBL expression resulted in the increased expression of TGF-beta target genes, PAI-I and CDK inhibitors such as p15(INK4b) and p21(Cip1). Furthermore, we demonstrate that CBL is frequently overexpressed in human breast cancer tissues, and the loss of CBL decreases the tumorigenic activity of breast cancer cells in vivo. CBL directly binds to Smad3 through its proline-rich motif, thereby preventing Smad3 from interacting with Smad4 and blocking nuclear translocation of Smad3. CBL-b, one of CBL protein family, also interacted with Smad3 and knockdown of both CBL and CBL-b further enhanced TGF-beta transcriptional activity. Our findings provide evidence for a previously undescribed mechanism by which oncogenic CBL can block TGF-beta tumor suppressor activity. PMID- 22310291 TI - DNA methylation silences miR-132 in prostate cancer. AB - Silencing of microRNAs (miRNAs) by promoter CpG island methylation may be an important mechanism in prostate carcinogenesis. To screen for epigenetically silenced miRNAs in prostate cancer (PCa), we treated prostate normal epithelial and carcinoma cells with 5-aza-2'-deoxycytidine (AZA) and subsequently examined expression changes of 650 miRNAs by megaplex stemloop reverse transcription quantitative PCR. After applying a selection strategy, we analyzed the methylation status of CpG islands upstream to a subset of miRNAs by methylation specific PCR. The CpG islands of miR-18b, miR-132, miR-34b/c, miR-148a, miR-450a and miR-542-3p showed methylation patterns congruent with their expression modulations in response to AZA. Methylation analysis of these CpG islands in a panel of 50 human prostate carcinoma specimens and 24 normal controls revealed miR-132 to be methylated in 42% of human cancer cases in a manner positively correlated to total Gleason score and tumor stage. Expression analysis of miR-132 in our tissue panel confirmed its downregulation in methylated tumors. Re expression of miR-132 in PC3 cells induced cell detachment followed by cell death (anoikis). Two pro-survival proteins-heparin-binding epidermal growth factor and TALIN2-were confirmed as direct targets of miR-132. The results of this study point to miR-132 as a methylation-silenced miRNA with an antimetastatic role in PCa controlling cellular adhesion. PMID- 22310292 TI - Endothelial cell dysfunction and cytoskeletal changes associated with repression of p16(INK4a) during immortalization. AB - The immortalization process is a fundamental step in the development of most (if not all) human cancers, including the aggressive endothelial cell (EC)-derived malignancy angiosarcoma. Inactivation of the tumor suppressor p16(INK4a) and the development of multiple chromosomal abnormalities are features of angiosarcoma that are recapitulated during telomerase-mediated immortalization of human ECs in vitro. The present study used a panel of telomerase-immortalized bone marrow EC (BMEC) lines to define the consequences of inactivation of p16(INK4a) on EC function and to identify molecular changes associated with repression of p16(INK4a). In a comparison of two immortalized BMEC mass cultures and six clones, the cell lines that repressed p16(INK4a) showed a higher rate of proliferation and an impaired ability to undergo morphogenic differentiation and form vessel-like structures in vitro. Proteomic comparison of a p16(INK4a) negative and a p16(INK4a)-positive BMEC mass culture at early- and late-passage time points following transduction with telomerase reverse transcriptase (hTERT) revealed altered expression of cytoskeletal proteins, including vimentin and alpha-tropomyosin (alphaTm), in the immortal cells. Immunoblot analyses of a panel of 11 immortal clones showed that cells that lacked p16(INK4a) expression tended to accumulate more dramatic changes in these cytoskeletal proteins than cells that retained p16(INK4a) expression. This corresponded with aberrant cytoskeletal architectures among p16(INK4a)-negative clones, which featured thicker actin stress fibers and less fluid membrane ruffles than p16(INK4a) positive cells. A direct link between p16(INK4a) repression and defective EC function was confirmed by analysis of normal cells transfected with small interfering RNA (siRNA) targeting p16(INK4a). siRNA-mediated repression of p16(INK4a) significantly impaired random motility and vessel formation in vitro. This report is the first to demonstrate that ECs that repress the expression of p16(INK4a) are prone to defects in motility, morphogenesis and cytoskeletal organization. These defects are likely to reflect alterations that occur during the development of EC-derived malignancies. PMID- 22310293 TI - Inhibition of miR-9 de-represses HuR and DICER1 and impairs Hodgkin lymphoma tumour outgrowth in vivo. AB - MicroRNAs are important regulators of gene expression in normal development and disease. miR-9 is overexpressed in several cancer forms, including brain tumours, hepatocellular carcinomas, breast cancer and Hodgkin lymphoma (HL). Here we demonstrated a relevance for miR-9 in HL pathogenesis and identified two new targets Dicer1 and HuR. HL is characterized by a massive infiltration of immune cells and fibroblasts in the tumour, whereas malignant cells represent only 1% of the tumour mass. These infiltrates provide important survival and growth signals to the tumour cells, and several lines of evidence indicate that they are essential for the persistence of HL. We show that inhibition of miR-9 leads to derepression of DICER and HuR, which in turn results in a decrease in cytokine production by HL cells followed by an impaired ability to attract normal inflammatory cells. Finally, inhibition of miR-9 by a systemically delivered antimiR-9 in a xenograft model of HL increases the protein levels of HuR and DICER1 and results in decreased tumour outgrowth, confirming that miR-9 actively participates in HL pathogenesis and points to miR-9 as a potential therapeutic target. PMID- 22310294 TI - Validation of the Lacaine-Huguier predictive score for choledocholithiasis: prospective study of 380 patients. AB - The aim of this study was to validate the Lacaine-Huguier score for the prediction of asymptomatic choledocholithiasis. METHODS: The study enrolled patients over age 18 with symptomatic chronic or acute calculous cholecystitis. Patients already known to have common bile duct stones (CBDS), as evidenced by symptomatic presentation with acute cholangitis or acute gallstone pancreatitis, were not included. We compared the group of patients with a score less than 3.5 versus those with a score greater or equal to 3.5; we also compared the group of patients who underwent intraoperative cholangiography (IOC) with those who did not undergo IOC. The negative predictive value of the Lacaine-Huguier score was calculated. RESULTS: We note that 308 women and 72 men were consecutively enrolled between February 2008 to March 2009; the average age was 51+/-16.4 years. The score was less than 3.5 in 154 patients (40.5%). IOC was only performed in 135 of the 226 patients with a score greater or equal to 3.5; reasons for this included a very narrow cystic duct in 67 cases, preoperative miscalculation of the score in nine cases, a technical problem in eight cases, an unspecified reason in four cases, contraindication due to pregnancy in two cases, and intraoperative difficulties in one case. CBDS were detected by IOC in 18 cases. Performance of IOC lengthened the median operative time by 20 minutes. The median follow-up was 8 months (range: 0-30 months). Eleven patients were lost to follow-up (2.9%), six of these had a score less than 3.5. Two patients had residual common bile duct (CBD) stones, one of whom had a score less than 3.5. The negative predictive value was 99.4% (95% confidence interval (CI 95%)=[98 100%]). The risk of leaving a stone in the CBD was 0.6%. When data was analyzed according to the worst case scenario, the negative predictive value became 95.5% (CI 95%=[92-99%]) with a risk of residual CBDS of 4.5%. CONCLUSION: This study confirmed the validity of the Lacaine-Huguier score. When the score is less than 3.5, the surgeon can refrain from performing IOC with a risk of asymptomatic residual CBDS ranging from 0.6% to 4.5%. PMID- 22310296 TI - Effectiveness of a new bioequivalent formulation of oseltamivir (Enfluvir(r)) on 2010-2011 seasonal influenza viruses: an open phase IV study. AB - OBJECTIVE: The aim of this multicenter prospective study was to evaluate the efficacy of a new bioequivalent formulation of oseltamivir for the treatment of influenza A, influenza B, and H1N1 during the 2010-2011 influenza season. METHODS: We compared the symptoms and signs of 300 pediatric patients presenting to three university hospitals with an influenza-like illness between January and March 2011. Nasal swab specimens were collected from all children and tested by reverse-transcription polymerase chain reaction (RT-PCR) for influenza viruses. After randomization, half of the participants were prescribed oseltamivir, while the other half were observed conservatively. Forty patients who were followed-up for influenza prior to the study were also included in the evaluation. RESULTS: Influenza was confirmed by RT-PCR in 129 children, 71 of whom were prescribed oseltamivir. The durations of the symptoms fever, cough, nasal congestion, and rhinorrhea were significantly shorter for patients who were treated with oseltamivir compared with untreated patients (p<0.002 for all symptoms). Early initiation of oseltamivir therapy (within 48 h of the onset of symptoms) was associated with more favorable outcomes and an earlier recovery than in patients for whom treatment was delayed (beyond 48 h). Thirty-seven patients (28.7%) had H1N1, 44 (34.1%) had influenza A, 46 (35.7%) had influenza B, one (0.8%) had H1N1 plus influenza A, and one (0.8%) had influenza A plus influenza B viruses. In the comparison of the duration of symptoms according to the different virus types, a statistically significant difference was only observed in patients with influenza B who had a longer duration of cough (p<0.001), nasal congestion (p<0.001), and rhinorrhea (p<0.001). CONCLUSIONS: Oseltamivir is an effective treatment for the management of seasonal influenza and H1N1, and should be initiated immediately without waiting for laboratory confirmation of diagnosis. PMID- 22310297 TI - Genetic engineering in biomimetic composites. AB - Composites represent a class of materials with properties that are obtained by combining the functions of different components. Combining soft and stiff components without losing toughness is typically very difficult with current synthetic tools. There are many natural materials for which this problem has been solved. Examples such as wood and seashells have inspired many scientists to seek tougher, stronger and lighter materials. This review describes how genetic engineering can help in building new composites with better properties. Specifically, we emphasize that functional molecules can be engineered by following the design principles of natural composite materials. This field is emerging but has already shown promising results and much progress in the next few years is expected. PMID- 22310298 TI - Characterization of human cytochrome P450 induction by pesticides. AB - Pesticides are a large group of structurally diverse toxic chemicals. The toxicity may be modified by cytochrome P450 (CYP) enzyme activity. In the current study, we have investigated effects and mechanisms of 24 structurally varying pesticides on human CYP expression. Many pesticides were found to efficiently activate human pregnane X receptor (PXR) and/or constitutive androstane receptor (CAR). Out of the 24 compounds tested, 14 increased PXR- and 15 CAR-mediated luciferase activities at least 2-fold. While PXR was predominantly activated by pyrethroids, CAR was, in addition to pyrethroids, well activated by organophosphates and several carbamates. Induction of CYP mRNAs and catalytic activities was studied in the metabolically competent, human derived HepaRG cell line. CYP3A4 mRNA was induced most powerfully by pyrethroids; 50 MUM cypermethrin increased CYP3A4 mRNA 35-fold. CYP2B6 was induced fairly equally by organophosphate, carbamate and pyrethroid compounds. Induction of CYP3A4 and CYP2B6 by these compound classes paralleled their effects on PXR and CAR. The urea herbicide diuron and the triazine herbicide atrazine induced CYP2B6 mRNA more than 10-fold, but did not activate CAR indicating that some pesticides may induce CYP2B6 via CAR-independent mechanisms. CYP catalyzed activities were induced much less than the corresponding mRNAs. At least in some cases, this is probably due to significant inhibition of CYP enzymes by the studied pesticides. Compared with human CAR activation and CYP2B6 expression, pesticides had much less effect on mouse CAR and CYP2B10 mRNA. Altogether, pesticides were found to be powerful human CYP inducers acting through both PXR and CAR. PMID- 22310299 TI - Tales of the autophagy crusaders. AB - The second EMBO Conference Series meeting on 'Autophagy in Health and Disease' took place in November 2011 in Israel. It brought together researchers from around the globe to cover the biogenesis of the autophagosome, as well as related topics including the regulation of autophagy, selective autophagy and the role of autophagy in disease and cell death. PMID- 22310301 TI - NC-AFM contrast formation on the calcite (1014) surface. AB - Calcite, the most stable polymorph of calcium carbonate, is one of the most abundant simple salts in the geological environment. Consequently, its natural (1014) cleavage plane has been studied extensively by a wide range of surface sensitive techniques, giving indications for two reconstructions, namely a (2 * 1) and a so-called 'row-pairing' reconstruction. The existence of the (2 * 1) reconstruction has been discussed controversially in the literature, but is now confirmed as a true surface property. In contrast, a comprehensive discussion on the existence of the row-pairing reconstruction is lacking so far.Here, we present a non-contact atomic force microscopy (NC-AFM) study of the (1014) calcite surface performed in an ultra-high vacuum. We discuss a broad variety of different NC-AFM contrasts and present a comprehensive classification scheme. This scheme encompasses a total of 12 different contrast modes. Atomically resolved NC-AFM images are shown, giving experimental evidence for 10 of these contrast modes. In particular, some of these modes allow for identification of the two surface reconstructions while others do not. This variety in appearances provides an explanation for the seemingly contradicting observations in the literature. Based on a detailed investigation of the influence of tip termination and interaction regime, we further analyse the existence of the row-pairing reconstruction. PMID- 22310300 TI - The FIH hydroxylase is a cellular peroxide sensor that modulates HIF transcriptional activity. AB - Hypoxic and oxidant stresses can coexist in biological systems, and oxidant stress has been proposed to activate hypoxia pathways through the inactivation of the 'oxygen-sensing' hypoxia-inducible factor (HIF) prolyl and asparaginyl hydroxylases. Here, we show that despite reduced sensitivity to cellular hypoxia, the HIF asparaginyl hydroxylase--known as FIH, factor inhibiting HIF--is strikingly more sensitive to peroxide than the HIF prolyl hydroxylases. These contrasting sensitivities indicate that oxidant stress is unlikely to signal hypoxia directly to the HIF system, but that hypoxia and oxidant stress can interact functionally as distinct regulators of HIF transcriptional output. PMID- 22310302 TI - Norovirus GII.4 and GII.7 capsid sequences undergo positive selection in chronically infected patients. AB - Norovirus has become an important cause for infectious gastroenteritis. Particularly genotype II.4 (GII.4) has been shown to spread rapidly and causes worldwide pandemics. Emerging new strains evade population immunity and lead to high norovirus prevalence. Chronic infections have been described recently and will become more prevalent with increasing numbers of immunocompromized patients. Here, we studied norovirus evolution in three chronically infected patients, two genotypes II.4 and one II.7. A 719 and 757 nt region was analyzed for GII.4 and GII.7, respectively. This covers the entire hypervariable P2 domain of the VP1 capsid gene. Genetic variability at given and between different time points was assessed. Evolutionary adaptation was analyzed by Bayesian sampling of genealogies. This analysis clearly demonstrated positive selection rather than incidental drift for all three strains. The GII.7 and one GII.4 strain accumulated on average 5-9 mutations per 100 days, most of them non-synonymous. This is a much higher evolutionary rate than observed for noroviruses on a global level. Our data demonstrate that norovirus quasispecies are positively selected in chronically infected patients. The numbers of intraindividual amino acid mutations acquired in the capsid gene are similar to those separating consecutive GII.4 epidemic strains. Evolution in a given, chronically infected individual may thus generate novel genotypes at risk to expedite global evolution particularly for slowly evolving genotypes, as GII.7. PMID- 22310303 TI - Gait analysis post anterior cruciate ligament reconstruction: knee osteoarthritis perspective. AB - Individuals with anterior cruciate ligament (ACL) reconstruction are at increased risk to develop knee osteoarthritis (OA). Gait analysis describing kinetics of the lower extremity during walking and stair use (stair ascent and stair descent) can provide insight to everyday dynamic knee joint loading. In this study, we compared lower extremity gait patterns of those with ACL reconstruction (>1 year) to a control group. Fifteen ACL reconstructed individuals and 17 healthy controls participated in this study. Knee extensor and flexor strength were assessed. Using inverse dynamics, lower extremity moments were calculated during the stance phase of walking and during two steps of stair ascent and descent. Univariate ANOVA was used to test for main effects between (1) injured leg and control group and (2) non-injured leg and control group. Student paired t-tests were used to determine differences between the injured and non-injured leg. Those with ACL reconstruction exhibited reduced initial knee flexion angles during stair descent, reduced knee extension moments during stair descent and stair ascent (second step), and increased hip extension moments during stair ascent (second step) and walking as compared to controls. Knee flexor strength was significantly reduced in the ACL group, but no differences were found in knee extensor strength. No kinematic or kinetic differences were observed between the injured and non-injured leg of the ACL group. Walking and stair ambulation highlight altered joint loading in those with ACL reconstruction surgery. Individuals appeared to compensate for lower knee extension moments by increasing hip extension moments. Furthermore, the load distribution on the articular cartilage is likely shifted as evidenced by reduced knee flexion angles in the ACL reconstructed leg. PMID- 22310304 TI - Experimental assessment of the effects of gastrointestinal parasites on offspring quality in chinstrap penguins (Pygoscelis antarctica). AB - Parasites reduce host fitness and consequently impose strong selection pressures on their hosts. It has been hypothesized that parasites are scarcer and their overall effect on hosts is weaker at higher latitudes. Although Antarctic birds have relatively low numbers of parasites, their effect on host fitness has rarely been investigated. The effect of helminth parasitism on growth rate was experimentally studied in chinstrap penguin (Pygoscelis antarctica) nestlings. In a total of 22 two-nestling broods, 1 nestling was treated with anthelminthics (for cestodes and nematodes) while its sibling was left as a control. Increased growth rate was predicted in de-wormed nestlings compared to their siblings. As expected, 15 days after treatment, the experimental nestlings had increased body mass more than their siblings. These results show a non-negligible negative effect of helminth parasites on nestling body condition that would presumably affect future survival and thus fitness, and it has been suggested there is a strong relationship between body mass and mortality in chinstrap penguins. PMID- 22310305 TI - Electroconvulsive seizure, but not imipramine, rapidly up-regulates pro-BDNF and t-PA, leading to mature BDNF production, in the rat hippocampus. AB - Electroconvulsive therapy is the most effective treatment for antidepressant resistant depression, although its mechanism has not been fully elucidated. Previous studies have demonstrated that electroconvulsive seizures (ECS) induce expression of brain-derived neurotrophic factor (BDNF) in the rat hippocampus. However, in contrast with mature BDNF (mBDNF) known to have antidepressant effects, its precursor (pro-BDNF) has harmful effects on neurons. We therefore hypothesized that efficient processing of pro-BDNF is a critical requirement for the antidepressant effects of ECS. We found that single administration of ECS rapidly increased not only hippocampal levels of pro-BDNF but also those of prohormone convertase 1 (PC1) and tissue-plasminogen activator (t-PA), which are proteases involved in intra- and extracellular pro-BDNF processing, respectively. Interestingly, pro-BDNF and t-PA levels were increased in hippocampal synaptosomes after single ECS, suggesting their transport to secretory sites. In rats receiving 10-d repeated ECS, accumulation of pro-BDNF and a resultant increase in mBDNF levels were observed. While t-PA levels increased and accumulated following repeated ECS, PC1 levels did not, suggesting that intracellular processing capacity is limited. Finally, chronic administration of imipramine significantly increased mBDNF levels, but not pro-BDNF and protease levels, indicating that the therapeutic mechanism of imipramine differs from that of ECS. Taken together, these results suggest that, while intra- and extracellular proteases are involved in pro-BDNF processing in single ECS, t-PA plays a dominant role following repeated ECS. Such efficient pro-BDNF processing as well as strong induction of BDNF expression may contribute to the antidepressant effects of ECS. PMID- 22310306 TI - Deficits in selective attention in symptomatic Huntington disease: assessment using an attentional blink paradigm. AB - BACKGROUND: Impaired selective attention in Huntington disease (HD) may manifest as difficulty in identifying a single target embedded among a series of distractors in rapid serial visual presentation tasks. METHOD: We used an attentional blink (AB) paradigm to examine whether attentional control is impaired in symptomatic HD. Fourteen HD patients and 13 age-matched healthy controls performed a rapid serial visual presentation task in which 2 targets (T1 and T2) and numerous distractors were presented in rapid succession. We assessed the accuracy of T1 identification and the AB (impaired T2 detection after the correct identification of T1). RESULTS: Among the HD patients, identification of T1 was significantly impaired and AB was significantly larger but not longer. The HD patients also made significantly more random errors. CONCLUSIONS: Frontostriatal or frontoparietal dysfunction is likely to compromise attentional control in HD, such that well-masked and rapidly presented target stimuli are difficult to detect and identify, especially as the difficulty level increases. Although we previously reported no AB deficits in presymptomatic HD, with manifest disease we found that the progressive frontoparietal cortical changes compromise attentional control mechanisms. PMID- 22310307 TI - Ipsilateral neglect from a subcortical lesion: effects of spatial position, distractors, and repeated trials. AB - OBJECTIVES: This report describes a patient with right putaminal hemorrhage who showed ipsilateral (right-sided) neglect. BACKGROUND: Although lesions to subcortical regions may result in contralateral hemispatial neglect, ipsilateral neglect from putaminal damage has not been reported. It has been posited that ipsilateral neglect from unilateral frontal lesions may be induced by a contralateral attentional grasp. This patient's putaminal hemorrhage may have induced frontal dysfunction with an attentional grasp. METHODS: Because distracting stimuli, as well as close (vs. far) spatial position, may alter an attentional grasp and because fatigue may compromise the ability to disengage, we tested the patient with repeated trials of line bisection in peripersonal (close) and extrapersonal (far) space with left-sided, right-sided, and both-sided distractors. RESULTS: The patient's leftward bias increased with repeated trials, particularly with those in the close condition and with left-sided distractors. CONCLUSIONS: Right putaminal hemorrhage may produce ipsilateral neglect. Our patient's putaminal-white matter injury may have induced frontal dysfunction, and, with repeated trials, his right basal ganglia-frontal network may have fatigued. This fatigue, together with left-sided distractors in the close condition, seemed to increase his contralateral attentional grasp. PMID- 22310308 TI - Mechanics of myosin function in white muscle fibres of the dogfish, Scyliorhinus canicula. AB - The contractile properties of muscle fibres have been extensively investigated by fast perturbation in sarcomere length to define the mechanical characteristics of myofilaments and myosin heads that underpin refined models of the acto-myosin cycle. Comparison of published data from intact fast-twitch fibres of frog muscle and demembranated fibres from fast muscle of rabbit shows that stiffness of the rabbit myosin head is only ~62% of that in frog. To clarify if and how much the mechanical characteristics of the filaments and myosin heads vary in muscles of different animals we apply the same high resolution mechanical methods, in combination with X-ray diffraction, to fast-twitch fibres from the dogfish (Scyliorhinus canicula). The values of equivalent filament compliance (C(f)) measured by X-ray diffraction and in mechanical experiments are not significantly different; the best estimate from combining these values is 17.1 +/- 1.0 nm MPa( 1). This value is larger than Cf in frog, 13.0 +/- 0.4 nm MPa(-1). The longer thin filaments in dogfish account for only part of this difference. The average isometric force exerted by each attached myosin head at 5 degrees C, 4.5 pN, and the maximum sliding distance accounted for by the myosin working stroke, 11 nm, are similar to those in frog, while the average myosin head stiffness of dogfish (1.98 +/- 0.31 pN nm(-1)) is smaller than that of frog (2.78 +/- 0.30 pN nm(-1)). Taken together these results indicate that the working stroke responsible for the generation of isometric force is a larger fraction of the total myosin head working stroke in the dogfish than in the frog. PMID- 22310309 TI - Copper-dependent regulation of NMDA receptors by cellular prion protein: implications for neurodegenerative disorders. AB - N-Methyl-D-aspartate (NMDA) receptors mediate a wide range of important nervous system functions. Conversely, excessive NMDA receptor activity leads to cytotoxic calcium overload and neuronal damage in a wide variety of CNS disorders. It is well established that NMDA receptors are tightly regulated by a number of cell signalling pathways. Recently, it has been shown that NMDA receptor activity is modulated by cellular prion protein (PrP(C)) in a copper-dependent manner. Here we give an overview of the current state of knowledge concerning the novel concept of potent modulation of this receptor's kinetics by copper ions, and the interplay between NMDA receptors and PrP(C) in the context of neurological diseases such as Alzheimer's disease, epilepsy, pain and depression. PMID- 22310310 TI - Nitric oxide and passive limb movement: a new approach to assess vascular function. AB - Passive limb movement elicits a robust increase in limb blood flow (LBF) and limb vascular conductance (LVC), but the peripheral vascular mechanisms associated with this increase in LBF and LVC are unknown. This study sought to determine the contribution of nitric oxide (NO) to movement-induced LBF and LVC and document the potential for passive-limb movement to assess NO-mediated vasodilatation and therefore NO bioavailability. Six subjects underwent passive knee extension with and without nitric oxide synthase (NOS) inhibition via intra-arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA). LBF was determined second-by-second by Doppler ultrasound, and central haemodynamics were measured by finger photoplethysmography. Although L-NMMA did not alter the immediate increase (initial ~9 s) in LBF and LVC, NOS blockade attenuated the peak increase in LBF (control: 653 +/- 81; L-NMMA: 399 +/- 112 ml(-1) min(-1), P = 0.03) and LVC (control: 7.5 +/- 0.8; L-NMMA: 4.1 +/- 1.1 ml min(-1) mmHg(-1), P = 0.02) and dramatically reduced the overall vasodilatory and hyperaemic response (area under the curve) by nearly 80% (LBF: control: 270 +/- 51; L-NMMA: 75 +/- 32 ml, P = 0.001; LVC: control: 2.9 +/- 0.5; L-NMMA: 0.8 +/- 0.3 ml mmHg(-1), P < 0.001). Passive movement in control and L-NMMA trials evoked similar increases in heart rate, stroke volume, cardiac output and a reduction in mean arterial pressure. As movement-induced increases in LBF and LVC are predominantly NO dependent, passive limb movement appears to have significant promise as a new approach to assess NO mediated vascular function, an important predictor of cardiovascular disease risk. PMID- 22310311 TI - Advanced in vitro approach to study neurovascular coupling mechanisms in the brain microcirculation. AB - An understanding of the signalling events underlying neurovascular coupling mechanisms in the brain is a crucial step in the development of novel therapeutic approaches for the treatment of cerebrovascular-associated disorders. In this study we present an enhanced in vitro brain slice preparation from male Wistar rat cortical slices that incorporates haemodynamic variables (flow and pressure) into parenchymal arterioles resulting in the development of myogenic tone (28% from maximum dilatation). Moreover, we characterized flow-induced vascular responses, resulting in various degrees of vasoconstrictions and the response to 10 mM K(+) or astrocytic activation with the mGluR agonist, t-ACPD (100 MUM), resulting in vasodilatations of 33.6+/-4.7% and 38.6+/-4.6%, respectively. Using fluorescence recovery, we determined perfusate velocity to calculate diameter changes under different experimental pH conditions. Using this approach, we demonstrate no significant differences between diameter changes measured using videomicroscopy or predicted from the velocity values obtained using fluorescence recovery after photobleaching. The model is further validated by demonstrating our ability to cannulate arterioles in two brain regions (cortex and supraoptic nucleus of the hypothalamus). Altogether, we believe this is the first study demonstrating successful cannulation and perfusion of parenchymal arterioles while monitoring/estimating luminal diameter and pressure under conditions where flow rates are controlled. PMID- 22310312 TI - Postsynaptic mechanisms of CO(2) responses in parafacial respiratory neurons of newborn rats. AB - The parafacial respiratory group (pFRG) in the rostral ventrolateral medulla of the newborn rat is predominantly composed of pre-inspiratory (Pre-I) neurons and is involved in respiratory rhythm generation. The subgroup located close to the ventral surface (at least partially overlapping the retrotrapezoid nucleus, RTN) expresses the Phox2b transcription factor and responds to hypercapnic stimulation with strong depolarization, which suggests it has a role in central chemoreception. Although a CO(2) response of pFRG/RTN neurons has been confirmed in the presence of tetrodotoxin (TTX), it is unknown whether the depolarization involved in this response is induced by a direct postsynaptic response of pFRG/RTN neurons or by any presynaptic components mediated by Ca(2+)-dependent mechanisms. In this study, we examined the effects of ATP or substance P receptor antagonists on hypercapnic responses of rostral pFRG/RTN neurons. We tested effects of Cd(2+) and low Ca(2+)-high Mg(2+) in the presence of TTX. The experiments were performed in in vitro brainstem-spinal cord preparations from newborn rats in which Pre-I neurons reflect the discharge pattern of the pFRG. We found that ATP receptor and substance P receptor antagonists do not block membrane potential responses to hypercapnic stimulation (2%->8%) of pFRG/RTN neurons in the rostral parafacial region.Moreover, rostral pFRG/RTN neurons were depolarized by hypercapnia under conditions where the contribution of presynaptic components was inhibited in the presence of TTX and Cd(2+) or in a low Ca(2+) high Mg(2+) solution containing TTX and Cd(2+). All cases (except some cases in a low Ca(2+)-high Mg(2+) solution) of membrane depolarization by hypercapnic stimulation were accompanied with an increase in input resistance. These neurons were predominantly Phox2b immunoreactive. Our findings suggest that the response of pFRG/RTN neurons to hypercapnia is induced by direct action on the postsynaptic membrane via closing of K(+) channels. PMID- 22310313 TI - Firing patterns of spontaneously active motor units in spinal cord-injured subjects. AB - Involuntary motor unit activity at low rates is common in hand muscles paralysed by spinal cord injury. Our aim was to describe these patterns of motor unit behaviour in relation to motoneurone and motor unit properties. Intramuscular electromyographic activity (EMG), surface EMG and force were recorded for 30 min from thenar muscles of nine men with chronic cervical SCI. Motor units fired for sustained periods (>10 min) at regular (coefficient of variation <= 0.15, CV, n =19 units) or irregular intervals (CV>0.15, n =14). Regularly firing units started and stopped firing independently suggesting that intrinsic motoneurone properties were important for recruitment and derecruitment. Recruitment (3.6 Hz, SD 1.2), maximal (10.2 Hz, SD 2.3, range: 7.5-15.4 Hz) and derecruitment frequencies were low (3.3 Hz, SD 1.6), as were firing rate increases after recruitment (~20 intervals in 3 s). Once active, firing often covaried, promoting the idea that units received common inputs.Half of the regularly firing units showed a very slow decline (>40 s) in discharge before derecruitment and had interspike intervals longer than their estimated after hyperpolarisation potential (AHP) duration (estimated by death rate and breakpoint analyses). The other units were derecruited more abruptly and had shorter estimated AHP durations. Overall, regularly firing units had longer estimated AHP durations and were weaker than irregularly firing units, suggesting they were lower threshold units. Sustained firing of units at regular rates may reflect activation of persistent inward currents, visible here in the absence of voluntary drive, whereas irregularly firing units may only respond to synaptic noise. PMID- 22310314 TI - The voltage dependence of I(h) in human myelinated axons. AB - HCN channels are responsible for I(h), a voltage-gated inwardly rectifying current activated by hyperpolarization. This current appears to be more active in human sensory axons than motor and may play a role in the determination of threshold. Differences in I(h) are likely to be responsible for the high variability in accommodation to hyperpolarization seen in different subjects. The aim of this study was to characterise this current in human axons, both motor and sensory. Recordings of multiple axonal excitability properties were performed in 10 subjects, with a focus on the changes in threshold evoked by longer and stronger hyperpolarizing currents than normally studied. The findings confirm that accommodation to hyperpolarization is greater in sensory than motor axons in all subjects, but the variability between subjects was greater than the modality difference. An existing model of motor axons was modified to take into account the behaviour seen with longer and stronger hyperpolarization, and a mathematical model of human sensory axons was developed based on the data collected. The differences in behaviour of sensory and motor axons and the differences between different subjects are best explained by modulation of the voltage dependence, along with a modest increase of expression of the underlying conductance of I(h). Accommodation to hyperpolarization for the mean sensory data is fitted well with a value of -94.2 mV for the mid-point of activation (V(0.5)) of I(h) as compared to -107.3 mV for the mean motor data. The variation in response to hyperpolarization between subjects is accounted for by varying this parameter for each modality (sensory: -89.2 to -104.2 mV; motor -87.3 to -127.3 mV). These voltage differences are within the range that has been described for physiological modulation of I(h) function. The presence of slowly activated I(h) isoforms on both motor and sensory axons was suggested by modelling a large internodal leak current and a masking of the Na(+)/K(+)-ATPase pump activity by a tonic depolarization. In addition to an increased activation of I(h), the modelling suggests that in sensory axons the nodal slow K(+) conductance is reduced, with consequent depolarization of resting membrane potential, and action potential of shorter duration. PMID- 22310315 TI - Synthetic localized calcium transients directly probe signalling mechanisms in skeletal muscle. AB - The contribution of Ca2+-induced Ca2+ release (CICR) to trigger muscle contraction is controversial. It was studied on isolated muscle fibres using synthetic localized increases in Ca2+ concentration, SLICs, generated by two photon photorelease from nitrodibenzofuran (NDBF)-EGTA just outside the permeabilized plasma membrane. SLICs provided a way to increase cytosolic [Ca2+] rapidly and reversibly, up to 8 MUM, levels similar to those reached during physiological activity. They improve over previous paradigms in rate of rise, locality and reproducibility. Use of NDBF-EGTA allowed for the separate modification of resting [Ca2+], trigger [Ca2+] and resting [Mg2+]. In frog muscle, SLICs elicited propagated responses that had the characteristics of CICR. The threshold [Ca2+] for triggering a response was 0.5 MUM or less. As this value is much lower than concentrations prevailing near channels during normal activity, the result supports participation of CICR in the physiological control of contraction in amphibian muscle. As SLICs were applied outside cells, the primary stimulus was Ca2+, rather than the radiation or subproducts of photorelease. Therefore the responses qualify as 'classic' CICR. By contrast, mouse muscle fibres did not respond unless channel-opening drugs were present at substantial concentrations, an observation contrary to the physiological involvement of CICR in mammalian excitation-contraction coupling. In mouse muscle, the propagating wave had a substantially lower release flux, which together with a much higher threshold justified the absence of response when drugs were not present. The differences in flux and threshold may be ascribed to the absence of ryanodine receptor 3 (RyR3) isoforms in adult mammalian muscle. PMID- 22310316 TI - Negative visualization of DNA in agarose gel by eosin Y and its related mechanism. AB - We report here a sensitive and environmentally benign technique for the visualization of DNA by using eosin Y, which appeared as a transparent and colorless band under the opaque gel matrix background. As low as 0.2-0.6 ng of DNA can be visualized within 1 h, similar to that of the most commonly used ethidium bromide stain. Furthermore, the mechanism of the newly developed method was also described. According to the results, it can be concluded that the complex between DNA and eosin Y is mainly formed by the function of groove binding, but not intercalate itself into the double helix structure of DNA. PMID- 22310317 TI - Diffusion-weighted MR imaging within 24 h post-injury after traumatic spinal cord injury: a qualitative meta-analysis between T2-weighted imaging and diffusion weighted MR imaging in 18 patients. AB - STUDY DESIGN: Only few studies have been published about diffusion-weighted imaging (DWI) within 24 h of traumatic spinal cord injury (tSCI). OBJECTIVES: The purpose of this study was to compare the imaging findings from conventional magnetic resonance imaging (MRI) and DWI in seven tSCI patients with findings in the existing literature. METHODS: Seven patients with tSCI at neurologic levels C2-T10 were examined with conventional MRI and DWI within 24 h post-injury. DWI was obtained with a b-factor of 1000 s mm(-2). American Spinal Injury Association (ASIA) scores and Spinal Cord Independence Measurement (SCIM) II item 12 after 12 months were collected. In addition, MEDLINE was searched from 1995 to 2010 to identify clinical tSCI studies reporting on MRI, DWI and apparent diffusion coefficient maps within 24 h post-injury to perform a meta-analysis. Images obtained with a b-factor of 1000 s mm(-2) were compared with lower b-factors. Differences were calculated using chi (2) tests. RESULTS: No associations were identified between the images of the seven tSCI patients and ASIA or SCIM II scores. Eighteen SCI patients (11 from the retrieved publications) were included in the meta-analysis. The detection rates of hyperintense signals on T2-weighted and DW imaging did not show significant differences at 94 and 72%, respectively. In addition, there were no significant differences in detection rates or diffusion abnormalities between subjects in whom DW images were obtained with a maximum b-factor of 1000 or <1000 s mm(-2). CONCLUSION: Our analysis suggests that T2-weighted and DW imaging have comparable detection rates for spinal cord damage in tSCI patients within 24 h post-injury. PMID- 22310318 TI - Brown-sequard syndrome after endovascular embolization of vertebral hemangioma. AB - STUDY DESIGN: Several causes of Brown-Sequard syndrome have been described. Endovascular embolization can be used to treat symptomatic vertebral hemangiomas. We describe a previously undocumented case of Brown-Sequard syndrome followed by endovascular embolization with microcoils of a vertebral hemangioma. We also provide a clinical-radiological correlation of this finding and review the relevant literature. CASE REPORT: A 39-year-old male was referred to our hospital for endovascular treatment of a right T9 hemivertebral hemangioma with compromise of the spinal canal. Fifteen minutes after the procedure, the patient developed right lower limb weakness and numbness on the left leg. The emergency magnetic resonance imaging (MRI) of the spine showed no abnormalities. Five days later, a new spinal MRI revealed an infarction in the right half of the spinal cord at T6 and T7 level. This stroke was probably caused by a microcoil ended up in the right sulcocommisural artery. One week after surgery, the patient was able to raise the right leg against gravity, but sensory deficit showed no improvement. CONCLUSIONS: To the best of our knowledge this is the first case of a Brown Sequard syndrome related to vertebral hemangioma embolization, a relatively safe technique with no important complications made known until this report. Clinicians should always weight the benefits with the potential devastating complications of this therapeutic option. PMID- 22310319 TI - International Spinal Cord Injury Pain (ISCIP) Classification: Part 2. Initial validation using vignettes. AB - STUDY DESIGN: International validation study using self-administered surveys. OBJECTIVES: To investigate the utility and reliability of the International Spinal Cord Injury Pain (ISCIP) Classification as used by clinicians. METHODS: Seventy-five clinical vignettes (case histories) were prepared by the members of the ISCIP Classification group and assigned to a category by consensus. Vignettes were incorporated into an Internet survey distributed to clinicians. Clinicians were asked, for each vignette, to decide on the number of pain components present and to classify each using the ISCIP Classification. RESULTS: The average respondent had 86% of the questions on the number of pain components correct. The overall correctness in determining whether pain was nociceptive was 79%, whereas the correctness in determining whether pain was neuropathic was 77%. Correctness in determining if pain was musculoskeletal was 84%, whereas for visceral pain, neuropathic at-level spinal cord injury (SCI) and below-level SCI pain it was 85%, 57% and 73%, respectively. Using strict criteria, the overall correctness in determining pain type was 68% (versus an expected 95%), but with maximally relaxed criteria, it increased to 85%. CONCLUSIONS: The reliability of use of the ISCIP Classification by clinicians (who received minimal training in its use) using a clinical vignette approach is moderate. Some subtypes of pain proved challenging to classify. The ISCIP should be tested for reliability by applying it to real persons with pain after SCI. Based on the results of this validation process, the instructions accompanying the ISCIP Classification for classifying subtypes of pain have been clarified. PMID- 22310320 TI - Editorial note on: Diagnostic value of diffusion-weighted MR imaging for acute stage of spine cord injury. PMID- 22310321 TI - A comparison of patients' and physiotherapists' expectations about walking post spinal cord injury: a longitudinal cohort study. AB - STUDY DESIGN: A longitudinal cohort study. OBJECTIVE: The primary objective of this study was to compare the expectations that patients with recent spinal cord injury (SCI) had about walking 1 year from injury with the expectations of their physiotherapists. SETTING: Two Sydney SCI units. METHODS: A consecutive series of 47 patients admitted to the metropolitan SCI units was recruited. Using the mobility scale, expectations of the patients and their physiotherapists about walking at 1 year from SCI were recorded at the time of admission to rehabilitation. Ability to walk was then assessed at 1 year from the SCI. RESULTS: On admission to rehabilitation, 31 patients expected to walk about their homes at 1 year post SCI, but only 18 (58%) of these patients did so. In contrast, physiotherapists expected 21 patients to be able to walk about their homes at 1 year post SCI, with 17 (81%) of these patients doing so. Similarly, whereas 21 patients expected to walk about the community at 1 year post SCI, only 11 (52%) of these patients did so. Physiotherapists expected 8 patients to walk about the community at 1 year post SCI and 7 (88%) of these patients did so. The differences between patients' and physiotherapists' expectations about walking were statistically significant (P<0.001). CONCLUSION: There is a high degree of disagreement between patients' and physiotherapists' expectations about walking at 1 year post SCI. Differences between patients' and physiotherapists' expectations about walking are potentially problematic and requires research to identify appropriate management strategies. PMID- 22310323 TI - Association between periodontitis and systemic bone mineral density in Japanese community-dwelling postmenopausal women. AB - OBJECTIVE: The purpose of this cross-sectional study was to evaluate the association between loss of attachment (LA) which is clinical index of periodontitis and bone mineral density (BMD) of the lumbar vertebrae and femur measured with dual energy X-ray absorptiometry (DXA) in Japanese community dwelling postmenopausal women. SUBJECTS AND METHODS: Subjects were 374 [corrected] women aged 55-74. The oral cavity was divided into 6 areas according to the WHO's method for the determination of the clinical attachment level score (CALscore); the LA was measured at 6 sites using a WHO probe in 17, 16, 11, 26, 27, 37, 36, 31, 46, and 47, and the values were recorded in mm. Then, we assessed BMD of the lumbar vertebrae (L2-L4) and femur (femoral neck, proximal part) by DXA. Based on these data, analysis of covariance was used to estimate relation between periodontitis and systemic BMD status excluding effect of age. Multiple linear regression analysis was used to estimate relation between periodontitis and BMD adjusted for 17 variables. RESULTS: Significant differences were observed in the mean value between the mean CALscore=0 and CALscore>=1 groups in the Z value in lumbar vertebrate (106.9+/-18.7 vs. 102.3+/-1.0, p<0.05, t-test). Multiple regression analysis was conducted using the mean LA as dependent variable. Lumbar vertebral BMD (regression coefficient: B=-1.039+/-0.379, p=0.007), femoral neck BMD (B=-1.332+/-0.627, p=0.034), and proximal femoral BMD (B=-1.329+/-0.536, p=0.014) all exhibited a significant negative correlation with the mean LA. CONCLUSION: A significant negative correlation was observed between periodontal disease and truncal bone BMD in this study. PMID- 22310324 TI - [Assessing the contribution of a standardized method in defining the tumor bed using surgical clips in breast cancer]. AB - PURPOSE OF THE STUDY: The objective of this study was to compare prospectively the delineations of tumour bed after breast conserving surgery from two techniques for defining the target volume. PATIENTS AND METHODS: Sixteen patients treated by lumpectomy with development of surgical clips were included. For each patient, four radiation oncologists delineated the clinical target volume (CTV boost) following its own method (technique 1) or using a predefined methodology (technique 2), the diameter to be applied around each clip relative to the risk of local recurrence. Factors taken into account to adjust the volume were tumour size, age, surgical margins and the presence of extensive ductal carcinoma. We then analyzed the factors varying the volume and variation of delineation for each method by calculating the concordance index: Kappa index and overlap. RESULTS: For all 16 patients, the volume delineated was nearly identical: 29.65 cm(3) with technique 1 and 33.54 cm(3) with technique 2 (P=0.6). The correlation was higher with technique 2 over technique 1, with KI from 0.146 to 0.285 (P=0.0001) and an OV of 0.302 to 0.458 (P=0.0002). CONCLUSION: Our study shows that within the same institute, there is a great variability in CTV delineation boost, even in the presence of surgical clips. A standardized approach to adjusting the volume of relapse risk factors has improved the consistency. PMID- 22310325 TI - Genomic tics in tourette syndrome. PMID- 22310326 TI - Arsenic decreases RXRalpha-dependent transcription of CYP3A and suppresses immune regulators in hepatocytes. AB - Arsenite is critical pharmacologically as a treatment for advanced stage blood cancer. However, environmental exposure to arsenic results in multiple diseases. Previous studies have shown that arsenic decreases expression of CYP3A, a critical drug metabolizing enzyme in human and rat liver. In addition, acute and chronic arsenic exposure in liver stimulates an inflammatory response. Our work has shown that arsenite decreases nuclear levels of RXRalpha the nuclear receptor that, as a heterodimer partner with PXR, transactivates the CYP3A gene. These results suggest that arsenite decreases transcription of CYP3A by decreasing RXRalpha. The present report shows that exposure to 5 MUM arsenite decreased the activity of a rat CYP3A promoter luciferase reporter in HepG2 cells. The activity of a RARE-luciferase reporter, that is transactivated by the retinoic acid receptor (RAR)/RXRalpha, was also decreased. Previous studies have shown that arsenic in the concentration range of 2-5 MUM affects CYP3A mRNA. When rifampicin treated primary human hepatocyte cultures were exposed to arsenite concentrations as low as 50 nM, CYP3A mRNA was decreased. Treatment of primary human hepatocytes with the proteasome inhibitor MG132 increased RXRalpha suggesting the involvement of the proteasome pathway in regulation of RXRalpha. Finally, arsenic induces a pro-inflammatory response in liver. Surprisingly, we show that in hepatocytes arsenite decreases expression of two inflammatory mediators, TNF and VEGF, an effect that is not predicted from suppression of RXRalpha activity. PMID- 22310328 TI - Imaging and manipulation of adatoms on an alumina surface by noncontact atomic force microscopy. AB - Noncontact atomic force microscopy (NC-AFM) has been performed on an aluminum oxide film grown on NiAl(110) in ultrahigh vacuum (UHV) at low temperature (5 K). Results reproduce the topography of the structural model, unlike scanning tunnelling microscopy (STM) images. Equipped with this extraordinary contrast the network of extended defects, which stems from domain boundaries intersecting the film surface, can be analysed in atomic detail. The knowledge of occurring surface structures opens up the opportunity to determine adsorption sites of individual adsorbates on the alumina film. The level of difficulty for such imaging depends on the imaging characteristics of the substrate and the interaction which can be maintained above the adsorbate. Positions of single adsorbed gold atoms within the unit cell have been determined despite their easy removal at slightly higher interaction strength. Preliminary manipulation experiments indicate a pick-up process for the vanishing of the gold adatoms from the film surface. PMID- 22310327 TI - Toddlers learn words in a foreign language: the role of native vocabulary knowledge. AB - The current study examined monolingual English-speaking toddlers' (N=50) ability to learn word-referent links from native speakers of Dutch versus English, and second, whether children generalized or sequestered their extensions when terms were tested by a subsequent speaker of English. Overall, children performed better in the English than in the Dutch condition; however, children with high native vocabularies successfully selected the target object for terms trained in fluent Dutch. Furthermore, children with higher vocabularies did not indicate their comprehension of Dutch terms when subsequently tested by an English speaker whereas children with low vocabulary scores responded at chance levels to both the original Dutch speaker and the second English speaker. These findings demonstrate that monolingual toddlers with proficiency in their native language are capable of learning words outside of their conventional system and may be sensitive to the boundaries that exist between language systems. PMID- 22310331 TI - Biobanking: shifting the analogy from consent to surrogacy. PMID- 22310332 TI - New "first families": the psychosocial impact of new genetic technologies. PMID- 22310336 TI - Branchiobdellidan infestation on endangered white-clawed crayfish (Austropotamobius pallipes) in the UK. AB - Branchiobdellidans or crayfish worms are clitellate annelids and ectosymbionts of freshwater crayfish. An investigation of branchiobdellidan infestation was undertaken in a population of endangered white-clawed crayfish (Austropotamobius pallipes) in the river Aire, UK. Thirty two percent of animals were infested either by the adult parasite or their cocoons (n=107). Parasite burden increased with host size, but did not differ with sex. Observations of crayfish gill tissue revealed a strong positive relationship between melanization of filaments and parasite prevalence and burden. Taxonomic identification revealed that 1 species of branchiobdellidan was present, Branchiobdella astaci. The first sequences were generated for this species and phylogenetically analysed alongside published sequences for 5 other branchiobdellidan species in Europe. The position of B. astaci within the genus Branchiobdella was confirmed, and it was found to cluster as a sister group to B. parasita. PMID- 22310337 TI - Erlotinib after failure of gefitinib treatment of more than 6 months in advanced non-small cell lung cancer. PMID- 22310338 TI - Molecular profiling for CUP cancers: are we there yet? PMID- 22310339 TI - Administration of 24-h intravenous infusions of trabectedin in ambulatory patients with mesenchymal tumors via disposable elastomeric pumps: an effective and patient-friendly palliative treatment option. AB - BACKGROUND: Patients with progressive mesenchymal tumours after standard chemotherapy have poor outcome. Trabectedin is approved in Europe as 24-h intravenous (i.v.) infusion q3w in this setting. We report the use of disposable elastomeric pumps for ambulatory treatment with trabectedin. MATERIAL AND METHODS: Pre-treated sarcoma patients were offered trabectedin 1.5 mg/m(2) as 24 h i.v. infusion via port catheter, either as inpatients using electronic pumps or as outpatients using the Baxter LV10 pump. Co-medication consisted of antiemetics including dexamethasone. RESULTS: 21/28 patients with distant metastasis and/or local relapse elected outpatient therapy and received 130 cycles (median 3, range 1-24). Dose reductions were done in 60 cycles, mainly due to laboratory adverse events (AEs). Best response (Response Evaluation Criteria in Solid Tumours (RECIST)) was 4 cases of confirmed partial remission (PR), 6 cases of stable disease (SD), and 11 cases of progressive disease (PD). Grade 3/4 (Common Toxicity Criteria (CTC)) AEs were limited to 1 case each of haemorrhage and lung embolism; other AEs were in line with published trabectedin experience. 1 port catheter contamination required replacement, 1 catheter thrombosis occurred and 1 extravasation due to needle dislocation was observed. CONCLUSIONS: Outpatient administration of trabectedin as 24-h infusion using Baxter LV10 pumps is preferred by the vast majority of patients; it is feasible, safe, effective, cost efficient, and should be considered as routine practice in this clinical setting. PMID- 22310340 TI - Effectiveness of erlotinib in advanced non-small cell lung cancer in cases of gefitinib resistance after treatment of more than 6 months. AB - BACKGROUND: There have been reports on the use of erlotinib in non-small cell lung cancer (NSCLC) patients after gefitinib resistance occurs, and it has been stated that erlotinib may be beneficial in patients with long stable disease (SD) previously treated with gefitinib. PATIENTS AND METHODS: We retrospectively studied gefitinib-resistant NSCLC patients with favorable clinical features, who received erlotinib following disease progression after gefitinib treatment of more than 6 months. RESULTS: A total of 21 patients with NSCLC were included. Partial response was seen in 2 cases (9%), SD in 6 cases (19%), and progressive disease (PD) in 13 cases (62%). Disease control (DC) was achieved with erlotinib in 8 cases (36%). The median survival time (MST) was 369 days in DC cases and 133 days in PD cases. There were no statistical differences between DC cases and PD cases in terms of MST relative to sex, smoking and skin rash. CONCLUSION: Subsequent erlotinib therapy is one of the therapeutic options in the treatment of gefitinib-resistant NSCLC in which prior gefitinib has shown long-term SD of more than 6 months. PMID- 22310341 TI - Efficacy of the CMFVP regimen in patients with metastatic breast cancer previously treated with anthracycline and taxane. AB - BACKGROUND: The aim of this retrospective study was to assess the efficacy and safety of the relatively old lowcost CMFVP regimen (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisolone) as compared to newer and more costly chemotherapeutic agents. PATIENTS AND METHODS: An analysis of the medical records of female patients with metastatic breast cancers treated with a CMFVP combination at the Shaare Zedek Medical Center (SZMC) was performed. 32 patients with measurable metastatic disease were included in the analysis. The median age was 59.9 years (range 36-102 years). 20 of the patients had previously been treated with both anthracyclines and taxanes. RESULTS: Therapy was generally well tolerated and toxicity manageable. Median time to disease progression was 20.97 weeks (range 2-103 weeks). 6 patients (19%) demonstrated a partial response, and 7 patients (22%) had stable disease lasting 3 or more months for an overall clinical benefit of 41%. 4 of the 20 patients previously treated with both anthracyclines and taxanes had a partial response, and 4 patients had stable disease lasting 3 or more months for a clinical benefit of 40%. CONCLUSION: On the basis of this small retrospective survey, we conclude that CMFVP combination chemotherapy is both effective and safe in patients with metastatic breast cancer previously treated with both taxanes and anthracyclines. PMID- 22310342 TI - Borderline tumors of the ovary: clinical course and prognostic factors. AB - BACKGROUND: The prognosis in borderline tumors of the ovary (BOT) is generally favorable. However, some patients experience recurrence, and mortalities occur. There is a need to better characterize prognostic factors to be considered for individualized treatment planning. PATIENTS AND METHODS: The data of 158 consecutive patients who underwent surgery for BOT at a tertiary referral center for gynecologic oncology between 1997 and 2008 were retrospectively analyzed. RESULTS: Most patients had early stage disease, and advanced stages FIGO II/III only occurred in 23.4%. Serous histology was most frequent (68%), followed by mucinous histology (22%). All patients received surgery as initial treatment with no adjuvant systemic therapy. 37 patients (40.7% of the patients under the age of 50) had fertility-sparing surgery (FSS). Recurrent disease occurred in 18 (11.4%) patients, and 4 (2.5%) patients died. Independent risk factors for recurrence were FIGO stages > I (hazard ratio (HR) 37.1; 95% confidence interval (CI) 4.5 155.5), tumor rupture (HR 12.4; 95% CI 1.5-61.5), incomplete staging (HR 5.9; 95% CI 1.6-21.3), and FSS in patients < 50 years (HR 8.0; 95% CI 2.0-31.6). CONCLUSION: Intraoperative tumor rupture, incomplete staging, and FSS - all influenced by the surgeon - may impose a substantial recurrence risk. Therefore, careful counseling and balancing of risk and benefit are mandatory before therapy is applied, especially if FSS is planned. PMID- 22310343 TI - Metronomic oral cyclophosphamide in patients with advanced solid tumors. AB - BACKGROUND: Cure is rarely achieved in patients with advanced metastatic solid tumors, and quality of life including times without burdening therapies is an important endpoint. Metronomic oral cyclophosphamide (Cy) has been studied before and is a reasonable option. PATIENTS AND METHODS: 24 patients with a mean age of 64.4 years (range 36-82 years) were studied. 18 patients had breast cancer, 4 prostate cancer, 1 uterine carcinoma, and 1 carcinoma of unknown primary. RESULTS: All patients had advanced disease with a mean of 2 metastatic sites. Cy was given at a mean dosage of 52 mg daily. Time from diagnosis to start of Cy was 108.6 +/- 7.6 months, and from occurrence of metastatic disease to Cy 45.8 +/- 45.6 months. Patients had received a mean of 4.2 +/- 2.1 prior regimens for metastatic disease. The mean time to treatment failure was 6.4 +/- 5.4 months, and mean overall survival was 12.7 +/- 7.3 months. Patients received 2.1 +/- 1.4 further treatments upon progression. Main toxicities were grade 1 and 2 (n = 25); 3 patients had grade 3 nausea, leucopenia, and elevated gamma glutamyl transferase, respectively. CONCLUSION: Low-dose oral Cy is a reasonable, generally well tolerated, and inexpensive option for patients with advanced solid tumors. PMID- 22310344 TI - Bone marrow metastases in a patient with primary mediastinal non-seminomatous germ cell tumor - an unusual pattern of relapse. AB - BACKGROUND: Bone marrow is a very unusual site of metastasis for germ cell tumors. CASE REPORT: We report the case of a 21-year-old male patient who was treated with chemotherapy and secondary surgery for a primary mediastinal non seminomatous germ cell tumor (NSGCT). The patient achieved complete remission. However, 4 months after completion of therapy, he complained of rapidly worsening bone pain. No evidence for disease relapse was found in the computed tomography scan of thorax and abdomen, magnetic resonance imaging of the spine, or bone scan. A blood test revealed pancytopenia and elevated serum tumor markers. A bone marrow aspirate showed infiltration by tumor cells positive for AE1/AE3 and AFP confirming the diagnosis of isolated bone marrow metastatic relapse. Salvage chemotherapy was started and resulted in a rapid decrease of serum tumor markers. However, pancytopenia did not improve and the patient died of severe sepsis 3 weeks later. CONCLUSION: We report here the first case of isolated bone marrow metastatic relapse of an NSGCT. 2 other cases of bone marrow metastasis in patients with NSGCT have been reported. In these 2 cases, as in our patient, the primary site was not testicular but mediastinal suggesting a non-fortuitous association. PMID- 22310345 TI - Radiotherapy in the treatment of epididymal adenocarcinoma - case report. AB - BACKGROUND: Primary epididymal carcinoma is an extremely rare disease with a bad prognosis. We describe the first report of radiotherapy for definitive treatment of such a tumour. CASE REPORT: A 35-year-old man with a tumour of the epididymis underwent orchiectomy and elective retroperitoneal lymphadenectomy. Adenocarcinoma of the epididymis and lymph node metastasis were confirmed. The patient refused the suggested adjuvant chemotherapy and returned to our centre with a local recurrence after 6 months. We indicated palliative radiotherapy to the scrotal and groin region. Complete remission was achieved and continues 3.5 years after treatment. Late effects included teleangiectasia, fibrosis and thickening of subcutaneous tissue, and depigmentation in the groin, but the patient enjoys very good quality of life including penile erection. CONCLUSION: We presented very good results of radiotherapy in the treatment of this rare malignant disease. We achieved complete remission with a good quality of life and with tolerable chronic toxicity. PMID- 22310346 TI - Cutaneous recurrence of malignant mesothelioma of the tunica vaginalis testis: a rare case report. AB - BACKGROUND: Mesothelioma of the tunica vaginalis testis is a rare and aggressive cancer; fewer than 90 cases have been reported. It occurs in all age groups, but its highest incidence appears between 55 and 75 years of age. Less than 5% of all malignant mesotheliomas arise from the tunica vaginalis testis. CASE REPORT: The authors present a rare case of localized malignant mesothelioma of the tunica vaginalis testis. Diagnosis and treatment are described. CONCLUSION: Mesothelioma of the tunica vaginalis testis can be asymptomatic for a long time. In more than half of the cases, the clinical manifestations imitate a hydrocele or a tumor mass in the scrotum. Despite treatment, this tumor has a very poor prognosis with a median survival of 23 months. PMID- 22310347 TI - Matrix metalloproteinases and their role in oncogenesis: a review. AB - The extracellular matrix (ECM) provides a physical framework for the cells and functions as a gel medium. Remodeling of the ECM is crucial during physiological cell migration, proliferation, growth, and development. Thus, the interaction between cells and the ECM plays a key role in normal development and differentiation of organisms. However, remodeling of the ECM also occurs in many pathological states. Changes in the ECM are regulated by a system of proteolytic enzymes that are responsible for the proteolysis of a huge quantity of ECM components. Matrix metalloproteinases (MMPs) represent the main group of regulating proteases in the ECM. By regulating the composition and integrity of the ECM, this group of enzymes is essential for cell proliferation, differentiation, and processes of apoptosis. However, deregulation or activation of MMP expression is a feature of numerous pathologic conditions including tumorigenesis and metastasis. The aim of this article is to provide a brief overview of MMPs, their nomenclature and structure, and their role in the development of tumors and metastases. PMID- 22310348 TI - Identifying the primary site using gene expression profiling in patients with carcinoma of an unknown primary (CUP): a feasibility study from the GEFCAPI. PMID- 22310349 TI - Recombinant human bone morphogenetic protein-2 as an adjunct for spine fusion in a pediatric population. AB - BACKGROUND/AIMS: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is responsible for multiple different signaling processes including positive effects on bone formation and fusion. In 2002, rhBMP-2 was approved for use in anterior lumbar spinal fusion by the Food and Drug Administration. Since that time, rhBMP 2 use for spinal fusion has become widespread. The use of rh-BMP2 for pediatric spinal fusion, however, has not been widely reported. We report the experience of the use of rhBMP-2 for pediatric spinal fusion at the University of Florida. METHODS: Data on patients under the age of 18 years who underwent spinal fusion with rhBMP-2 as an adjunct were retrospectively collected. Of these, 17 met the inclusion criteria and were reviewed. Two patients did not have adequate postoperative imaging. Fifteen patients were included in the final review. RESULTS: All 15 patients showed osseous fusion. Complications included one CSF leak and one wound infection, one misplaced screw requiring revision, and one case of adjacent segment kyphosis requiring extension of the original construct. CONCLUSION: rhBMP-2 is a successful adjunct for fusion in pediatric patients. Many of these patients had congenital defects that historically decrease fusion rates. rhBMP-2 appears safe and has an associated high rate of osseous fusion. PMID- 22310352 TI - Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene. AB - Antipsychotic-induced weight gain (AIWG) may result in the metabolic syndrome in schizophrenia (SCZ) patients. Downstream variants of the melanocortin-4 receptor (MC4R) gene have been associated with obesity in various populations. Thus, we examined single-nucleotide polymorphisms (SNPs) in the MC4R region for association with AIWG in SCZ patients. Four SNPs (rs2229616, rs17782313, rs11872992 and rs8087522) were genotyped in 224 patients who underwent treatment for SCZ and were evaluated for AIWG for up to 14 weeks. We compared weight change (%) across genotypic groups using analysis of covariance for three SNPs (r2<=0.8). European-ancestry patients who were rs8087522 A-allele carriers (AG+AA) on clozapine gained significantly more weight than non-carriers (P=0.027, n=69). These observations were marginal after correction for multiple testing. We performed in vitro electrophoretic mobility-shift assay that suggested that the presence of the A-allele may create a transcription factor-binding site. Further investigation is warranted for both these exploratory findings. PMID- 22310353 TI - Beyond single-marker analyses: mining whole genome scans for insights into treatment responses in severe sepsis. AB - Management of severe sepsis, an acute illness with high morbidity and mortality, suffers from the lack of effective biomarkers and largely empirical predictions of disease progression and therapeutic responses. We conducted a genome-wide association study using a large randomized clinical trial cohort to discover genetic biomarkers of response to therapy and prognosis utilizing novel approaches, including combination markers, to overcome limitations of single marker analyses. Sepsis prognostic models were dominated by clinical variables with genetic markers less informative. In contrast, evidence for gene-gene interactions were identified for sepsis treatment responses with genetic biomarkers dominating models for predicting therapeutic responses, yielding candidates for replication in other cohorts. PMID- 22310351 TI - Pharmacogenomics in colorectal cancer: a genome-wide association study to predict toxicity after 5-fluorouracil or FOLFOX administration. AB - The development of genotyping technologies has allowed for wider screening for inherited causes of variable outcomes following drug administration. We have performed a genome-wide association study (GWAS) on 221 colorectal cancer (CRC) patients that had been treated with 5-fluorouracil (5-FU), either alone or in combination with oxaliplatin (FOLFOX). A validation set of 791 patients was also studied. Seven SNPs (rs16857540, rs2465403, rs10876844, rs10784749, rs17626122, rs7325568 and rs4243761) showed evidence of association (pooled P-values 0.020, 9.426E-03, 0.010, 0.017, 0.042, 2.302E-04, 2.803E-03) with adverse drug reactions (ADRs). This is the first study to explore the genetic basis of inter-individual variation in toxicity responses to the administration of 5-FU or FOLFOX in CRC patients on a genome-wide scale. PMID- 22310355 TI - [Introduction]. PMID- 22310356 TI - [Methodological characteristics of the Catalan Health Survey 2006]. AB - The Health Survey of Catalonia (ESCA) gives essential population information for health planning and evaluation. On the edition of 2006, 18,126 non institutionalized persons were interviewed. The sample design is complex with the aim to guarantee the representatively also in small geographic areas with interest in health and service planning. There are certain novelties in the third edition such as the relevance given to the territory, questionnaires adaptations to the interviewed population and new subject areas studied. This paper describes the useful methodological aspects for the ESCA 2006 users. In the first part we describe the sample design, questioners, field work, interviewer's formation, codification and quality micro data control. In the second part compound variables, used tools and their references are shown. And the third part describes the indicators construction since the sample design determines the use of weighing and elevation factors to obtain representative estimation values. PMID- 22310357 TI - [Impact of chronic diseases on life expectancy in the population of Catalonia, Spain, in 1994 and 2006]. AB - This paper analyzes the changes in the prevalence of selected chronic conditions and their impact on the life expectancy in the population of Catalonia. The chronic conditions selected are: hypertension, diabetes, stroke, heart diseases, chronic bronchitis, asthma, chronic allergies, musculoskeletal system diseases, and anxiety/depression. The prevalence of these diseases is estimated from data collected by the Health Survey of Catalonia in 1994 and 2006. The most frequently chronic conditions among the Catalan population are the musculoskeletal disorders, the high blood pressure and the depression and/or anxiety. By the analysis of the changes in the life expectancy free of chronic disorders, this study shows the impact of these disorders in the life expectancy. The burden of the chronic morbidity in our community, and its impact on the health systems, requires further studies to increase the knowledge of this phenomenon. PMID- 22310358 TI - [Individual and population-based risk in mental health in Catalonia, Spain]. AB - Mental health disorders are health problems with a high health, social and economic impact and with relevant effects on the quality of life of both the patients and their families. The objective of this article is to measure the prevalence of mental disorders in Catalonia and to analyze changes the changes in the results obtained in the Goldberg General Health Questionnaire in the Catalan Health Survey editions developed in 1994 and 2006. The prevalence of population at risk of suffering of a mental health disorder does not differ in both years (12.6% in 1994 and 11.6% in 2006). Women showed a higher risk than men in both surveys. Paradoxically, it is amongst the people without risk where the highest number of cases of depression, anxiety, antidepressant use, psychiatry visits or bad perception of health was declared. The results agreed with the risk and prevention paradox and are relevant at the time of designing strategies for mental health disorders prevention. PMID- 22310359 TI - [Prevalence and burden of visual impairment in Catalonia, Spain]. AB - The aim of this work is to determine the prevalence of visual impairment in Catalonia and analyze inequalities in vision. Cross sectional study in the population having >= 15 years of age (7,881 men and 8,045 women) based on data from the Encuesta de Salud de Cataluna 2006. Logistic regression models were used to calculate the adjusted odds ratio by age, civil state, level of studies, income and working situation with a confidence interval (CI) of 95%. A 4.7% (CI 95% 4.4-5.0) of the population of Catalonia, a 5.3% of female (CI 95% 4.8-5.8), and 4.1% of men (CI 95% 3.7-4.5) state that they have poor vision. The most unfavourable situations of self-reported poor vision by the Catalan population correspond to the elderly and women with lower levels of both studies and income. PMID- 22310360 TI - [The health of men and women in Catalonia, Spain. Are changes occurring?]. AB - The aim of this work is to show the changes observed in the health profile according to gender in 2006 with respect to 1994 of the population of Catalonia, through the comparison of data obtained in 1994 and 2006 from the Encuesta de Salud de Cataluna. The increase of the level of studies of the population has tended to comparing both sexes. The pattern of the social classes has been invested, so that in 2006 the proportion of women who place themselves in the upper classes and intermediate is superior to that of the men, and the proportion of women belonging to the lower class is inferior to that of the men. The number of women who incorporate into the work and handicapped world has increased those who are declared housewives. The little healthy behaviors continue being more frequent among men but the proportion of smoker and sedentary women increased between 1994 and 2006. Women have a more preventive than men in relation to the taking of blood pressure and measurement of cholesterol levels. People who value their health as positive has increased, but maintains that the percentage of women is lower than in males. The women continue to have more chronic diseases, mental disorders and disabilities. In 2006, and in comparison with 1994, it is observed that in Catalonia the health profile by gender, wherein women have poorer perception of health status, greater number of chronic diseases and disabilities and greater risk of poor mental health than men. Unhealthy habits are still more prevalent among men with the exception of the sedentarism, which is more frequent among women. Women continue practicing preventive activities in greater proportion than men. PMID- 22310361 TI - [Dependency for activities of daily living in the elderly in Catalonia, Spain]. AB - The aim of this article is to estimate the disabilty prevalence for the activities of daily living (ADL), the socioeconomic and demographic characteristics and the use of health services, distinguishing between the population receiving assistance for ADL and not. Cross-sectional study (Encuesta de Salud de Cataluna [ESCA] 2006). We have analyzed 17 ADL. Differences among proportions are estimated with a 95% confidence interval to characterize the analysis groups. Logistic regression describes the explanatory variables about getting help or not. Disabilty prevalence for the ADL: 26.6% men and 48.2% in women. Of these, 79.6% is getting help. There is a socioeconomic gradient in prevalence, not being observed in relation to assistance or not. We must deepen our understanding of the phenomenon and its evolution to which the ESCA is an essential tool. PMID- 22310362 TI - [Health-related quality of life and factors associated with overweight and obesity in the pediatric population of Catalonia, Spain]. AB - The aim of this work is to describe the health-related quality of life (HRQOL), and to analyze the associated factors to overweight/obesity in a representative sample of the Catalan population 0-14 years old. Proxyrespondents answered the child's questionnaire of the Encuesta de Salud de Cataluna (ESCA) 2006 (n = 2.200). Variables analyzed were weight and height, the KIDSCREEN-10 HRQOL questionnaire, and also scales on risky behaviors, physical activity, frequency of fast food consumption, and number of hours of television viewing. Logistic regression models were adjusted. In 31% of children HRQOL was excellent/very good. Risky behaviors and restriction of activity were the associated factors to the best and the worst HRQOL. Maternal level of education and some habits and behaviors were associated to overweight/obesity. The ESCA contributes with useful information to monitor and to assess interventions addressed to the children population. PMID- 22310363 TI - [Health services' utilization patterns in Catalonia, Spain]. AB - The purpose of this article is disclose services utilization patterns among the Catalan population with particular emphasis on primary care, specialised care, hospital care and emergency care. A number of logistic regression models were used to explain the utilization of the various types of services. Variables in the analysis included self-perceived need, lifestyles, and sociodemographic variables. Separate analyses were performed for male, female, adults, and children as well as for the general population. Women use all types of services more often than men. Children and people over 64 are more frequent users of primary care. Primary care is also associated to lower socioeconomic conditions. Young adults and the migrant population in general are found to be under users of services, except of emergency care services. The use of specialised care is associated to the better-off, to those with university level education attainment, individual private insurance, and those living in the city of Barcelona. Hospital care is largely associated to need variables. The use of health services is explained by self-perceived need as well as by demographic, socioeconomic and geographical factors. PMID- 22310364 TI - [One more step in the study of social inequalities in primary care provision from a population-based perspective]. AB - Evaluation of Primary Care (PC) must include different perspectives. The objective of the study was to know the assessment of the PC in Catalonia and detecting whether or not a pattern of social inequality exists, through user's experience. A cross-sectional study was conducted, in a representative sample (n = 13,292) of the Catalonia population (aged 15), who identify a reference professional. It was studied an index of experience with PC by personal variables and variables about the reference professional. Negative binomial regression models (bivariate and multivariate) were adjusted to obtain the prevalence ratios and confidence intervals of 95%. The index gained an average of 71 (scale 0-100). A rating above 70 was associated with higher age, greater number of visits in the last year, more time with the same professional and living in an area of lower population density. Items with lower scores: telephone attention and availability of mental health services. We concluded that factors associated with a better experience are associated with more frequent visits to professionals. We did not detect social inequalities. PMID- 22310365 TI - [Satisfaction survey of CatSalut-PLAENSA((c)). Strategies to incorporate citizens' perception of the quality of the service in health policies]. AB - The aim of this work is to present the strategies, activities and results of satisfaction surveys Plan CatSalut- PLAENSA((c)) 2003-2010 that are making progress in improving the quality of health services. Since 2003, CatSalut has at its disposal the plan known as PLAENSA((c)) Satisfaction Surveys, a tool for assessment and improvement proposals addressed to the insurance services provided by contracted public entities. The plan follows 3 key strategies: systematic and objective policyholders' satisfaction measurement, related to the services received; release of improvement proposals according to a standardized model, including standardized monitoring, and promotion of equity through propagation among health centres and territories. Current assessment provided by the insured about most health services has been already collected, leading to more tan 2,500 projects of improvement which are being developed by the providers of the 7 health regions of Catalonia. PMID- 22310366 TI - [Trends in social inequalities in health in Catalonia, Spain]. AB - The aim of this work is to analyze the evolution of social class inequalities in men and women in health status, health related behaviours and utilization of health services in Catalonia between 1994 and 2006. This is a study of trends based on the analysis of the Encuesta de Salud de Cataluna. To examine the association between 12 dependent variables and social class in each survey, robust Poisson regression models were fitted. People belonging to manual class showed the worst indicators. Over the period, social class inequalities in health status and health services utilisation tended to remain constant or to decrease (performing breast cancer screening). Conversely, inequalities in smoking increased. In Catalonia there are social class inequalities in health, among men and women, that tend to remain stable over the years. PMID- 22310367 TI - [Health surveys in Catalonia, Spain: a literature review]. AB - The aim of this study is to analyze biomedical publications on health surveys (HS) in the Catalan territory from documents published in various bibliographic databases to 2010. Analysis of 1,287 HS documents on 3 bibliographic sources of information relating to Catalonia, between 1991 and 2010. Scientific papers on HS in the Catalan territory have been 196. We studied the variables related to the topic of the article published, the magazine publication of the survey, the characteristics of sampling and the sample size, geographical area and timing of the survey. The articles reviewed represent 15.23% of all original documents. Half of them have been published in Spanish journals, stressing Gaceta Sanitaria and Medicina Clinica and the most studied issues are health and lifestyles. A 40.8% clearly explicit the characteristics of the sample, the size of them range between 49 and 23,126 individuals. It is suggested that HS in Catalonia are useful for generating knowledge about health, lifestyle and health resource utilization of the population, and its disclosure among health experts and the public. PMID- 22310368 TI - Microscale oxygraphy reveals OXPHOS impairment in MRC mutant cells. AB - Given the complexity of the respiratory chain structure, assembly and regulation, the diagnostic workout for the identification of defects of oxidative phosphorylation (OXPHOS) is a major challenge. Spectrophotometric assays, that measure the activity of individual respiratory complexes in tissue and cell homogenates or isolated mitochondria, are highly specific, but their utilization is limited by the availability of sufficient biological material and intrinsic sensitivity. A further limitation is tissue specificity, which usually determines attenuation, or disappearance, in cultured fibroblasts, of defects detected in muscle or liver. We used numerous fibroblast cell lines derived from patients with OXPHOS deficiencies to set up experimental protocols required for the direct readout of cellular respiration using the Seahorse XF96 apparatus, which measures oxygen consumption rate (OCR) and extra-cellular acidification rate (ECAR) in 96 well plates. Results demonstrate that first level screening based on microscale oxygraphy is more sensitive, cheaper and rapid than spectrophotometry for the biochemical evaluation of cells from patients with suspected mitochondrial disorders. PMID- 22310369 TI - The neutrophil and systemic inflammation. PMID- 22310370 TI - Receptor targets of amacrine cells. AB - Amacrine cells are a morphologically and functionally diverse group of inhibitory interneurons. Morphologically, they have been divided into approximately 30 types. Although this diversity is probably important to the fine structure and function of the retinal circuit, the amacrine cells have been more generally divided into two subclasses. Glycinergic narrow-field amacrine cells have dendrites that ramify close to their somas, cross the sublaminae of the inner plexiform layer, and create cross talk between its parallel ON and OFF pathways. GABAergic wide-field amacrine cells have dendrites that stretch long distances from their soma but ramify narrowly within an inner plexiform layer sublamina. These wide-field cells are thought to mediate inhibition within a sublamina and thus within the ON or OFF pathway. The postsynaptic targets of all amacrine cell types include bipolar, ganglion, and other amacrine cells. Almost all amacrine cells use GABA or glycine as their primary neurotransmitter, and their postsynaptic receptor targets include the most common GABA(A), GABA(C), and glycine subunit receptor configurations. This review addresses the diversity of amacrine cells, the postsynaptic receptors on their target cells in the inner plexiform layer of the retina, and some of the inhibitory mechanisms that arise as a result. When possible, the effects of GABAergic and glycinergic inputs on the visually evoked responses of their postsynaptic targets are discussed. PMID- 22310371 TI - Amacrine cell-mediated input to bipolar cells: variations on a common mechanistic theme. AB - Feedback is a ubiquitous feature of neural circuits in the mammalian central nervous system (CNS). Analogous to pure electronic circuits, neuronal feedback provides either a positive or negative influence on the output of upstream components/neurons. Although the particulars (i.e., connectivity, physiological encoding/processing/signaling) of circuits in higher areas of the brain are often unclear, the inner retina proves an excellent model for studying both the anatomy and physiology of feedback circuits within the functional context of visual processing. Inner retinal feedback to bipolar cells is almost entirely mediated by a single class of interneurons, the amacrine cells. Although this might sound like a simple circuit arrangement with an equally simple function, anatomical, molecular, and functional evidence suggest that amacrine cells represent an extremely diverse class of CNS interneurons that contribute to a variety of retinal processes. In this review, I classify the amacrine cells according to their anatomical output synapses and target cell(s) (i.e., bipolar cells, ganglion cells, and/or amacrine cells) and discuss specifically our current understandings of amacrine cell-mediated feedback and output to bipolar cells on the synaptic, cellular, and circuit levels, while drawing connections to visual processing. PMID- 22310372 TI - Intrinsic properties and functional circuitry of the AII amacrine cell. AB - Amacrine cells represent the most diverse class of retinal neuron, comprising dozens of distinct cell types. Each type exhibits a unique morphology and generates specific visual computations through its synapses with a subset of excitatory interneurons (bipolar cells), other amacrine cells, and output neurons (ganglion cells). Here, we review the intrinsic and network properties that underlie the function of the most common amacrine cell in the mammalian retina, the AII amacrine cell. The AII connects rod and cone photoreceptor pathways, forming an essential link in the circuit for rod-mediated (scotopic) vision. As such, the AII has become known as the rod-amacrine cell. We, however, now understand that AII function extends to cone-mediated (photopic) vision, and AII function in scotopic and photopic conditions utilizes the same underlying circuit: AIIs are electrically coupled to each other and to the terminals of some types of ON cone bipolar cells. The direction of signal flow, however, varies with illumination. Under photopic conditions, the AII network constitutes a crossover inhibition pathway that allows ON signals to inhibit OFF ganglion cells and contributes to motion sensitivity in certain ganglion cell types. We discuss how the AII's combination of intrinsic and network properties accounts for its unique role in visual processing. PMID- 22310374 TI - EARS(r) (Evaluation of Auditory Responses to Speech): an internationally validated assessment tool for children provided with cochlear implants. AB - OBJECTIVES: The use of cochlear implants in the rehabilitation of hearing impaired patients is now widely established and offers great benefits for children. To evaluate these benefits, the Evaluation of Auditory Responses to Speech (EARS(r)) assessment tool was designed in 1995. The objectives of this study were to assess the auditory perceptual skills in a large paediatric population over time, as well as to provide standardised values. METHODS: An international multicentre study was conducted in 35 clinics from 1996 to 2009. During this period, 765 children were assessed with the EARS in 10 test intervals: pre-operative, first fitting and then 1, 3, 6, and 12 months after the first fitting and annually thereafter, up to a maximum period of 5 years. RESULTS: The auditory skills improved significantly over time for all speech perception tests and questionnaires as well as between single test intervals: pre operative to 6 months, 6 months to 1 year and 1 year to 2 years. Standardised values of the children stratified according to their age at implantation were calculated. CONCLUSIONS: The auditory perceptual skills significantly improved over time. The standardised values will help professionals set therapeutic goals and counsel parents accordingly. PMID- 22310373 TI - The role of starburst amacrine cells in visual signal processing. AB - Starburst amacrine cells (SBACs) within the adult mammalian retina provide the critical inhibition that underlies the receptive field properties of direction selective ganglion cells (DSGCs). The SBACs generate direction-selective output of GABA that differentially inhibits the DSGCs. We review the biophysical mechanisms that produce directional GABA release from SBACs and test a network model that predicts the effects of reciprocal inhibition between adjacent SBACs. The results of the model simulations suggest that reciprocal inhibitory connections between closely spaced SBACs should be spatially selective, while connections between more widely spaced cells could be indiscriminate. SBACs were initially identified as cholinergic neurons and were subsequently shown to contain release both acetylcholine and GABA. While the role of the GABAergic transmission is well established, the role of the cholinergic transmission remains unclear. PMID- 22310375 TI - Assessing a bioremediation strategy in a shallow coastal system affected by a fish farm culture--application of GIS and shellfish dynamic models in the Rio San Pedro, SW Spain. AB - An integrated multi-trophic aquaculture assessment for Pacific oyster (Crassostrea gigas) aquaculture as a bioremediation strategy in areas impacted by fish farm effluents in Rio San Pedro was assessed by combining geographic information system with carrying capacity models. Sites of 0.44 km(2) were evaluated considering constraints; physical factors, growth and survival factors, environmental quality factors, water and sediment quality criteria, factor suitability ranges, and Multi-Criteria Evaluation. Isleta and Flamenco are promising sites for oyster production, and Dorada is of marginal interest. Carbon and nitrogen removal from the water by algae and through detritus filtration was estimated. The biodeposition of organic material from longline leases was found to have little negative impact on sediment. The eutrophication results indicate that phytoplankton removal had a positive impact on water quality at the Dorada. This case study quantified the direct profitability and bioremediative environmental service advantages that fish-shellfish farms can have relative to fish monocultures. PMID- 22310376 TI - Three-dimensional scanning force/tunneling spectroscopy at room temperature. AB - We simultaneously measured the force and tunneling current in three-dimensional (3D) space on the Si(111)-(7 * 7) surface using scanning force/tunneling microscopy at room temperature. The observables, the frequency shift and the time averaged tunneling current were converted to the physical quantities of interest, i.e. the interaction force and the instantaneous tunneling current. Using the same tip, the local density of states (LDOS) was mapped on the same surface area at constant height by measuring the time-averaged tunneling current as a function of the bias voltage at every lateral position. LDOS images at negative sample voltages indicate that the tip apex is covered with Si atoms, which is consistent with the Si-Si covalent bonding mechanism for AFM imaging. A measurement technique for 3D force/current mapping and LDOS imaging on the equivalent surface area using the same tip was thus demonstrated. PMID- 22310377 TI - Retroclival epidural hematoma in a child affected by whiplash cervical injury: a typical case of a rare condition. AB - Traumatic posterior fossa epidural hematomas are uncommon lesions. Among these lesions, retroclival epidural hematomas (REDH) are particularly rare conditions that usually occur in the pediatric population due to predisposing anatomical features in this patient group. We describe a typical case of traumatic REDH from the mechanism of trauma to outcome. This 8-year-old girl was involved in a motor vehicle accident leading to whiplash cervical injury and cranial nerve palsy. Any children involved in a severe motor vehicle accident with such a sequence of events should raise suspicion for prompt diagnosis. PMID- 22310378 TI - Regulatory T-cell abnormalities and the global epidemic of immuno-inflammatory disease. AB - The incidence of autoimmune, allergic and inflammatory disease is increasing due to as yet unidentified environmental factors related to western living conditions. Here, I propose that alterations in the gut microbiome, acting via regulatory T cells (Tregs), may be responsible for this epidemic. Tregs control the threshold for peripheral antigen recognition via tonic downregulation of dendritic cell (DC) costimulation, and are also implicated in maintaining the tolerogenic function of DCs. In this model, minor perturbations in Treg number or function are predicted to lower the activation threshold, allowing proliferation and differentiation of self-reactive CD4T cells of too low an affinity to have undergone negative selection in the thymus. Failure to maintain the tolerogenic commitment of DCs exposed to commensal microbes and allergens could result in potentially pathogenic, allergic and inflammatory responses at epithelial surfaces. PMID- 22310379 TI - Serine protease inhibitors of parasitic helminths. AB - Serine protease inhibitors (serpins) are a superfamily of structurally conserved proteins that inhibit serine proteases and play key physiological roles in numerous biological systems such as blood coagulation, complement activation and inflammation. A number of serpins have now been identified in parasitic helminths with putative involvement in immune regulation and in parasite survival through interference with the host immune response. This review describes the serpins and smapins (small serine protease inhibitors) that have been identified in Ascaris spp., Brugia malayi, Ancylostoma caninum Onchocerca volvulus, Haemonchus contortus, Trichinella spiralis, Trichostrongylus vitrinus, Anisakis simplex, Trichuris suis, Schistosoma spp., Clonorchis sinensis, Paragonimus westermani and Echinococcus spp. and discusses their possible biological functions, including roles in host-parasite interplay and their evolutionary relationships. PMID- 22310380 TI - Dual polarisation interferometry for real-time, label-free detection of interaction of mercury(II) with mercury-specific oligonucleotides. AB - A real-time, label-free dual polarisation interferometry technique was used to investigate the interaction of Hg(2+) with a 21-mer T-rich oligonucleotide and further construct a Hg(2+) biosensor based on thymine-Hg(2+)-thymine coordination chemistry. PMID- 22310381 TI - DAG1, no gene for RNA regulation? AB - DAG1 encodes for a precursor protein that liberates the two subunits featured by the dystroglycan (DG) adhesion complex that are involved in an increasing number of cellular functions in a wide variety of cells and tissues. Aside from the proteolytic events producing the alpha and beta subunits, especially the former undergoes extensive "post-production" modifications taking place within the ER/Golgi where its core protein is both N- and O-decorated with sugars. These post-translational events, that are mainly orchestrated by a plethora of certified, or putative, glycosyltransferases, prelude to the excocytosis-mediated trafficking and targeting of the DG complex to the plasma membrane. Extensive genetic and biochemical evidences have been accumulated so far on alpha-DG glycosylation, while little is know on possible regulatory events underlying the chromatine activation, transcription or post-transcription (splicing and escape from the nucleus) of DAG1 or of its mRNA. A scenario is envisaged in which cells would use a sort of preferential, and scarcely regulated, route for DAG1 activation, that would imply fast mRNA transcription, maturation and export to the cytosol, and would prelude to the multiple time-consuming enzymatic post translational activities needed for its glycosylation. Such a provocative view might be helpful to trigger future work aiming at disclosing the complete molecular mechanisms underlying DAG1 activation and at improving our knowledge of any pre-translational step that is involved in dystroglycan regulation. PMID- 22310382 TI - A large deletion causes apparent homozygosity for the D1152H mutation in the cystic fibrosis transmembrane regulator (CFTR) gene. AB - We report the case of a patient with an apparent homozygosity for the D1152H mutation located in exon 18 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The parents had no personal history of cystic fibrosis (CF) and referred to our laboratory after the diagnosis of fetal bowel hyperechogenicity. The proband presented with meconium ileus and normal sweat chloride test. Sequencing of the CFTR exon 18 together with quantitative genomic assays, such as real-time PCR and the multiplex ligation probe amplification (MLPA) techniques, were performed and revealed that the father was heterozygous for the D1152H mutation and the mother carried a large deletion of the CFTR gene encompassing the genomic sequence including the same mutation. The child inherited D1152H from his father and the large deletion of the CFTR gene from his mother. We suggest that D1152H likely acts as a mild mutation with a dominant effect on the severe deletion of exon 18, considering that after 3 years of clinical examinations the child shows no classical signs and symptoms of CF. Not testing for large deletions in subjects with apparent homozygosity for a mutated CFTR allele could lead to the misidentification of CFTR mutation carrier status. PMID- 22310383 TI - Paradoxical role of C1561T glutamate carboxypeptidase II (GCPII) genetic polymorphism in altering disease susceptibility. AB - Glutamate carboxypeptidase II (GCPII) is predominantly expressed in brain, intestinal mucosa and prostate cancer in the form of three splice variants i.e. N acetylated-alpha-linked acidic dipeptidase (NAALADase), folyl poly-gamma glutamate carboxypeptidase (FGCP) and prostate specific membrane antigen (PSMA) respectively. Its inhibition was found to confer protection against certain neurological disorders and cancer. Despite the pivotal role of this enzyme, the most common polymorphism i.e. H475Y has not been explored comprehensively in all its splice variants. In this study, we have determined the role of this variant in different disease conditions such as breast and prostate cancers, autism, coronary artery disease (CAD) and miscarriages (N=1561). Genotyping was done by PCR-RFLP and dideoxy sequencing. Plasma folate levels were estimated by Axysm folate kit. GCPII expression was studied by semi-quantitative RT-PCR. In silico model was developed using PYMOL. We observed the protective role of H475Y variant in cancers [breast cancer; OR (95% CI): 0.81 (0.55-1.19), prostate cancer: OR (95% CI): 0.00 (0.00-0.66)], and in autism (OR (95% CI): 0.47 (0.21-1.03), whereas inflated risk was observed in CAD (OR (95% CI): 1.69 (1.20-2.37) and miscarriages [Maternal OR (95% CI): 3.26 (2.11-5.04); Paternal OR(95% CI): 1.99 (1.23-3.21)]. Further, this variant was found to impair the intestinal folate absorption in subjects with dietary folate intake in the lowest tertile (CC vs. CT in lowest tertile; 7.56+/-0.85ng/ml vs. 2.73+/-045ng/ml, p=0.005). In silico model of GCPII showed steric hindrance with H475Y resulting in stereochemical alteration of catalytic site, thus interfering with ligand binding. Statistically significant association was not observed between dietary folate levels and GCPII expression. However, a positive correlation was seen between plasma folate levels and GCPII expression (r=0.70, p<0.05). To conclude, our data suggests that GCPII H475Y variant shows inverse association with autism and cancer while showing positive association with CAD and miscarriages. PMID- 22310384 TI - Molecular characterization, tissue expression and nucleotide variation of the porcine AZ1 gene. AB - Antizyme 1 (AZ1) is a member of the antizyme family that is involved in many biological processes. As a natural inhibitor, AZ1 controls the normal level of polyamines, which is indispensable to cellular function. Our prior research showed that the expression of the AZ1 gene in Longissimus doris of Landrace pigs was higher (P<0.05) than in Lantang pigs. The AZ1 gene might be involved in the development of muscle and potentially serves as an important target for muscle improvement in pigs. In this study, the molecular characterization, tissue expression, and sequence variation of porcine AZ1 gene were analyzed. A 4082 bp sequence including the 5'-flanking region and gene sequence was obtained through RACE and sequencing. The genomic sequence of AZ1 gene consists of six exons and five introns. The mRNA of AZ1 gene contains three elements: 5'-untranslated regions (UTR, 79 bp), CDS (684 or 207 bp), and 3'-UTR (161 or 423 bp for the two transcripts). Three termination signals of AATAAA were found in the longer 3' UTR. The mRNA sequence of the AZ1 gene contained two ORFs with a frameshifting site at the 69th codon. The amino acid sequence from the porcine AZ1 gene was similar to other vertebrates and exhibited the highest similarity to cattle. The partial 5'-flanking region was 852 bp with typical cis-regulatory elements such as TATA boxes and CAAT boxes. By DNA pooling and sequencing, nine and 12 single nucleotide polymorphisms (SNPs) were detected in the 5'-flanking region and introns, respectively. Except the SNP at -713, the other eight SNPs were found in putative cis-acting elements and might alter the binding of trans-acting factors. Expression patterns showed that in Lantang pig, the AZ1 gene is differentially expressed in various tissues and displayed higher expression in lung and skeletal muscle. PMID- 22310386 TI - Polymorphisms of the insulin-like growth factor-binding protein 3 gene (IGFBP3) in gayal (Bos frontalis). AB - The gene coding for insulin-like growth factor-binding protein 3 (IGFBP3) is important for regulation of growth, development and metabolism in mammals. The present investigation was conducted to study nucleotide polymorphism of the IGFBP3 in gayal (Bos frontalis) and to compare the variations with those which occur in other ruminants. A fragment of 645 base pairs of the IGFBP3 covering a part of exon 2, the complete intron 2 and exon 3 and a part of intron 3 was amplified, sequenced (n=46) and digested (n=79) with HaeIII restriction enzyme from 125 collected gayal samples. Nine single nucleotide polymorphisms (SNPs) [C14T, A122C, C137T, G144C, C155T, G213A, C279A, G334A and G460A] were identified and located in intron 2, revealing high genetic variability. The alignment of nucleotide sequences was found to be very similar to those for other bovid species. Sequencing and HaeIII digestion showed that frequency of alleles C and A [consisting of fragments of sizes 56, 64, 228, 264, 282, 298 and 497 bp (CC genotype)] was 0.96 and 0.04 for the SNP C279A. Moreover, the genotype frequency of the SNP C279A in gayal was compared with that in other ruminants and it appears that this polymorphism may be associated with low fat content and rapid growth in this rare species. PMID- 22310385 TI - Structural and functional characterization of H2 haplotype MAPT promoter: unique neurospecific domains and a hypoxia-inducible element would enhance rationally targeted tauopathy research for Alzheimer's disease. AB - Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Extraneuronal plaque comprising mostly the amyloid beta peptide and intraneuronal tangles of hyperphosphorylated microtubule-associated tau protein (tau, gene MAPT) are typical of AD. Misfolded tau is also implicated in Parkinson's disease and frontotemporal dementia. We aim to understand the regulation of the human MAPT promoter by mapping its functional domains. We subcloned a 4868 base pair (bp) fragment from human BAC RPCI-11 100C5. Sequence analysis revealed an H2 haplotype MAPT promoter, 5'-UTR, and intronal fragment. Database analysis of the fragment showed 50%-75% homology with mouse and >90% with rhesus monkey. Comparison with human H1 sequences revealed differences that crossed predicted transcription factor sites. DNA-protein interaction studies by electrophoretic mobility shift assay suggested hypoxia response and an active specificity protein 1 (SP1) site in the 5'-untranslated region. Transfection of a series of MAPT promoter deletions revealed unique functional domains. The distal-most had different activities in neuronal vs. non-neuronal cells. We have cloned, sequenced, and functionally characterized a 4868bp fragment of the human MAPT 5' flanking region, including the core promoter region (-302/+4), neurospecific domains (-4364/-1992 and +293/+504, relative to +1 TSS), and a hypoxia-inducible element (+60/+84). Our work extended functional analysis of the MAPT sequence further upstream, and explores cell-type specificity of MAPT promoter activity. Finally, we provided direct comparison of likely transcription factor binding sites, which are useful to understand differences between H1/H2 pathogenic associations. PMID- 22310387 TI - Aberrant brain microRNA target and miRISC gene expression in the anx/anx anorexia mouse model. AB - The anorexia mouse model, anx/anx, carries a spontaneous mutation not yet identified and homozygous mutants are characterized by anorexia-cachexia, hyperactivity, and ataxia. In order to test if the microRNA function was altered in these mice, hypothalamus and cortex transcriptomes were evaluated and the data was analyzed taking into account the presence of microRNA target sites. Subsequent validation of the expression of a subset of miRISC coding genes and microRNA targets was performed by TaqMan real time PCR. In anx/anx hypothalamus we found that predicted microRNA targets were preferentially upregulated in a linearly dependent manner according to the number of microRNA target sites in each mRNA (p=10(-139)). Conversely, we observed that in anx/anx cortex mRNAs predicted to be targeted by microRNAs were preferentially downregulated (p<10( 74)), suggesting a de-regulation of genes targeted by microRNAs in two brain areas in anx/anx mice. A closer look to the mRNA transcriptome allowed us to identify upregulation of five miRISC genes, including Dgcr8 and Fmr1, and Ago2, which were later confirmed by real time PCR. The results suggest alteration of microRNA machinery expression in anx/anx mice and are consistent with its involvement in inflammatory/cancer-associated anorexia-cachexia. The data also support the previously reported link between microRNA machinery and ataxia. Further functional studies and the cloning of the anx gene should be pursued in order to elucidate the causality of microRNA machinery and microRNA target de regulation, its relationship with the anx/anx phenotype and to propose this mouse as a model for microRNA research. PMID- 22310388 TI - Molecular cloning, characterization and expression of heat shock protein 70 gene from the oyster Crassostrea hongkongensis responding to thermal stress and exposure of Cu(2+) and malachite green. AB - Heat shock protein 70 (HSP70) acts mostly as a molecular chaperone and plays a key role in the process of protecting cells by facilitating the folding of nascent peptides and the cellular stress response. The cDNA of the oyster Crassostrea hongkongensis hsp70 (designated chhsp70) was cloned with the techniques of homological cloning and rapid amplification of cDNA ends (RACE). The full-length chhsp70 cDNA was 2251bp, consisting of a 130bp 5'-UTR, 216bp 3' UTR with a canonical polyadenylation signal sequence AATAAA and a poly (A) tail, and an open reading frame of 1905bp, which encoded a polypeptide of 634 amino acids. Three classical HSP signature motifs were detected in ChHSP70, i.e., DLGTT S-V, IFDLGGGTFDVSIL and VVLVGGSTRIPKIQK. BLAST analysis revealed that the ChHSP70 shared high identity with other bivalve HSP70. The phylogenetic analysis indicated that the ChHSP70 was a member of the HSP70 family. The chhsp70 mRNA transcripts were quantified by fluorescent real time RT-PCR under both unstressed and stressed conditions, i. e., heat shock and exposure to Cu(2+) and malachite green. Basal expression level was similar in mantle, gill, digestive gland, and heart, but higher in muscle than that in the others. A similar trend showed that the chhsp70 mRNA expression significantly increased at 3-6h, then dropped and returned to control level at 24h in the five tissues and organs mentioned above after heat shock. A clearly time-dependent expression pattern of chhsp70 mRNA in digestive gland and gill of the oyster was observed after exposure of Cu(2+) and malachite green. In the two tissues, the chhsp70 mRNA level reached the maximum at 6h after malachite green exposure and on day 4 after Cu(2+) exposure, and then decreased progressively to the control level. The results indicated that ChHSP70 of the oyster is an inducible protein, and plays an important role in response to the Cu(2+) and malachite green polluted stress, so chhsp70 might be used as a potential molecular biomarker of above pollutants. PMID- 22310389 TI - KlRox1p contributes to yeast resistance to metals and is necessary for KlYCF1 expression in the presence of cadmium. AB - We have characterized the KlROX1 gene from Kluyveromyces lactis and verified that it does not regulate the hypoxic response in this yeast, oppositely to the Saccharomyces cerevisiae homologue ScROX1. The KlROX1 promoter is not regulated by KlHap1p or KlRox1p in response to changes aerobiosis/hypoxia. Besides, KlRox1p expression only partially represses ScANB1 in S. cerevisiae and does not regulate the ScANB1 and KlHEM13 promoters in K. lactis. KlRox1p does not interact either with KlTup1p or KlSsn6p or with their homologues ScTup1p and ScSsn6p, which are components of the general co-repressor factor that mediates the transcriptional repression exerted by ScRox1p in S. cerevisiae. We have found that KlROX1 mediates the response to arsenate and cadmium and, in the presence of cadmium, it is necessary for KlYCF1 expression, a gene encoding a protein with homology to the yeast cadmium and arsenite vacuolar transporter. EMSA assays show that KlRox1p binds, through its HMG domain, to a DNA sequence present in the KlYCF1 promoter. Although in S. cerevisiae the function of ScRox1p in cadmium resistance was already known and linked to regulation of ScFET4 expression, we have found that ScRox1p also regulates ScYCF1transcription and binds to its promoter. PMID- 22310391 TI - Gene expression profile of the cynobacterium synechocystis genome. AB - The expression of functional proteins plays a crucial role in modern biotechnology. The free-living cynobacterium Synechocystis PCC 6803 is an interesting model organism to study oxygenic photosynthesis as well as other metabolic processes. Here we analyze a gene expression profiling methodology, RCBS (the scores of relative codon usage bias) to elucidate expression patterns of genes in the Synechocystis genome. To assess the predictive performance of the methodology, we propose a simple algorithm to calculate the threshold score to identify the highly expressed genes in a genome. Analysis of differential expression of the genes of this genome reveals that most of the genes in photosynthesis and respiration belong to the highly expressed category. The other genes with the higher predicted expression level include ribosomal proteins, translation processing factors and many hypothetical proteins. Only 9.5% genes are identified as highly expressed genes and we observe that highly expressed genes in Synechocystis genome often have strong compositional bias in terms of codon usage. An important application concerns the automatic detection of a set of impact codons and genes that are highly expressed tend to use this narrow set of preferred codons and display high codon bias .We further observe a strong correlation between RCBS and protein length indicating natural selection in favor of shorter genes to be expressed at higher level. The better correlations of RCBS with 2D electrophoresis and microarray data for heat shock proteins compared to the expression measure based on codon usage difference, E(g) and codon adaptive index, CAI indicate that the genomic expression profile available in our method can be applied in a meaningful way to study the mRNA expression patterns, which are by themselves necessary for the quantitative description of the biological states. PMID- 22310390 TI - Negative regulation of human U6 snRNA promoter by p38 kinase through Oct-1. AB - Recruitment of Oct-1 protein to the octamer sequence of U6 promoter is critical for optimal transcription by RNA polymerase III. Here we report that p38 kinase inhibitors, SB202190 and SB203580, stimulated U6 promoter activity and this stimulation can be observed only in the presence of octamer sequence. SB202190 treated cell nuclear extract had about 50% increase in Oct-1 binding activity suggesting that the increased U6 promoter activity by p38 kinase inhibitor is mediated through Oct-1. Mutation in octamer sequence significantly reduced the SB202190-stimulated U6 promoter transcription and the distance between octamer and proximal sequence element of U6 promoter is also critical for the p38 kinase inhibitor-stimulated activity. Exogenous Oct-1 expression showed a concentration dependent activation of U6 promoter that was further stimulated by the p38 kinase inhibitors. When cells were treated with p38 kinase inducer, hydrogen peroxide or phorbol 12-myristate 13-acetate (PMA), U6 promoter activity was down regulated and this inhibition was reversed by p38 kinase inhibitors. Over-expression of p38alpha kinase down-regulated U6 promoter activity and this inhibition was further enhanced by PMA and p38 kinase inhibitors reversed this inhibition. p38 kinase inhibitor-treated cells had 50% more U6 RNA than the control cells. Taken together, our results show a negative correlation between the p38 kinase levels and Oct-1 binding on U6 promoter, suggesting that U6 promoter is negatively regulated by p38 kinase. PMID- 22310392 TI - Association between C3orf21, TP63 polymorphisms and environment and NSCLC in never-smoking Chinese population. AB - Recently, two genome-wide association studies in Asia identified gene polymorphisms known as rs4488809, rs9816619 in TP63 and rs2131877, rs952481 in C3orf21. It has been proposed that these polymorphisms are susceptibility loci for non-small cell lung cancer (NSCLC) development among Japanese and Korean populations. We ask whether susceptibility to NSCLC is limited to the Chinese population or whether the environment also affects genetic polymorphisms. We conducted a matched case-control study to explore this question. Results show that polymorphism of TP63 was not associated with NSCLC development, whereas variant genotypes of C3orf21 were nominally associated with a reduced risk of lung adenocarcinoma (OR=0.619, 95% CI=0.390-0.976). These results strongly suggest that environmental agents interact with human genetic polymorphism independent of ethnic background. In addition, the C3orf21 gene may be a potential susceptibility marker for lung adenocarcinoma independent of ethnic background and environmental agents. PMID- 22310393 TI - High levels of Paleolithic Y-chromosome lineages characterize Serbia. AB - Whether present-day European genetic variation and its distribution patterns can be attributed primarily to the initial peopling of Europe by anatomically modern humans during the Paleolithic, or to latter Near Eastern Neolithic input is still the subject of debate. Southeastern Europe has been a crossroads for several cultures since Paleolithic times and the Balkans, specifically, would have been part of the route used by Neolithic farmers to enter Europe. Given its geographic location in the heart of the Balkan Peninsula at the intersection of Central and Southeastern Europe, Serbia represents a key geographical location that may provide insight to elucidate the interactions between indigenous Paleolithic people and agricultural colonists from the Fertile Crescent. In this study, we examine, for the first time, the Y-chromosome constitution of the general Serbian population. A total of 103 individuals were sampled and their DNA analyzed for 104 Y-chromosome bi-allelic markers and 17 associated STR loci. Our results indicate that approximately 58% of Serbian Y-chromosomes (I1-M253, I2a-P37.2 and R1a1a-M198) belong to lineages believed to be pre-Neolithic. On the other hand, the signature of putative Near Eastern Neolithic lineages, including E1b1b1a1 M78, G2a-P15, J1-M267, J2-M172 and R1b1a2-M269 accounts for 39% of the Y chromosome. Haplogroup frequency distributions in Western and Eastern Europe reveal a spotted landscape of paleolithic Y chromosomes, undermining continental wide generalizations. Furthermore, an examination of the distribution of Y chromosome filiations in Europe indicates extreme levels of Paleolithic lineages in a region encompassing Serbia, Bosnia-Herzegovina and Croatia, possibly the result of Neolithic migrations encroaching on Paleolithic populations against the Adriatic Sea. PMID- 22310394 TI - Differential effects of extracellular matrix and mechanical strain on airway smooth muscle cells from ovalbumin- vs. saline-challenged Brown Norway rats. AB - The asthmatic airway is characterized by alterations in decorin and biglycan and increased airway smooth muscle (ASM). Further, the asthmatic airway may be subjected to abnormal mechanical strain. We hypothesized that ASM cells obtained from ovalbumin (OVA)--and saline (SAL)--challenged rats would respond differently to matrix and mechanical strain. ASMC were seeded on plastic, decorin or biglycan. Additional cells were grown on decorin, biglycan or collagen type 1, and then subjected to mechanical strain (Flexercell). The number of OVA ASMC was significantly greater than SAL ASM when seeded on plastic. A significant decrease was observed for both OVA and SAL ASMC seeded on decorin compared to plastic; the reduction in ASMC number was more modest for OVA. Biglycan decreased SAL ASMC number only. Strain reduced cell number for SAL and OVA ASMC grown on all matrices. Strain affected expression of beta1-integrin differently in OVA vs. SAL ASMC. These data suggest that matrix and mechanical strain modulate ASMC number; these effects are differentially observed in OVA ASMC. PMID- 22310395 TI - Modified Ollier transtrochanteric approach for the treatment of acetabular fractures. AB - The purpose of this retrospective clinical study was to evaluate the rates of wound and neurologic complications and clinically significant heterotopic ossification, Brooker stage 3 and 4, with the modified Ollier transtrochanteric approach for the treatment of acetabular fractures. The study group comprised 94 consecutive patients (95 acetabuli) who had unstable acetabular fractures requiring surgical fixation. All patients were treated with open reduction internal fixation via the Ollier approach by a single surgeon (L.E.D.). Demographic and clinical information regarding rates of wound and neurologic complications and remaining articular stepoff at fixation was obtained from a chart review. The degree of heterotopic ossification was graded from standard anteroposterior pelvis radiographs according to the Brooker classification. Six (6%) patients underwent reoperation for infection; however, only 3 (3%) of these patients had deep infections. Three (3%) patients had iatrogenic sciatic nerve injuries; only 1 patient had persistent sensory changes at final follow-up. Thirteen (18%) of the 73 patients with radiographs available for review at a minimum of 3-month follow-up had Brooker grade III heterotopic ossification and 1 (1%) patient had grade IV. Five (5%) patients underwent excision of heterotopic ossification. Fourteen (17%) of 81 patients had no radiographic union of the greater trochanteric osteotomy, but none of these patients required further surgery. The complication rates of the Ollier approach in this study compare favorably with alternative surgical approaches reported in large series. We believe this approach provides excellent exposure without increasing the risk of complications. PMID- 22310396 TI - Quantitative score system for the surgical decision on adult femoral neck fractures. AB - Surgical decision making for femoral neck fractures is currently based on factors such as patient age, fracture type, and medical condition, lacking a quantitative standard. The treatment protocol based on such qualitative assessment has poor operability, greatly affected by the surgeon's subjective factors. As a result, a quantitative score system (QSS) focusing on 5 factors--age, fracture type, bone mineral density, activities of daily living, and medical comorbidities--with a total score of 25 is designed to deal with adult femoral neck fractures. The higher the score, the worse the patient's physiological condition. According to our clinical experience, patients with 1 to 11 points should be treated with internal fixation; patients with 12 to 17 points with total hip arthroplasty (THA), and patients with 18 to 22 points with hemiarthroplasty. Patients with 22 to 25 points should be treated with internal fixation due to the high surgical risk of arthroplasty caused by poor physiological condition. Three hundred seventy-five adult femoral neck fractures were treated on the basis of QSS for this 2-year prospective study. Of these, 242 were treated with low-score internal fixation, 60 with THA, 55 with hemiarthroplasty, and 18 with high-score internal fixation. The revision rates 2 years postoperatively in the low-score internal fixation, THA, and hemiarthroplasty groups were 15.3%, 5.0%, and 5.5%, respectively, which were lower than those from a meta-analysis (internal fixation, 35%; THA, 16%). This QSS helps surgical decision making regarding the treatment choice for adult patients with femoral neck fractures, and good results in preliminary clinical practice have been achieved. PMID- 22310397 TI - Predictive value of preoperative digital templating in THA depends on the surgical experience of the performing physician. AB - Digital preoperative templating is increasingly used to predict the correct component size in total hip arthroplasty (THA). Experienced surgeons could avoid the new technique and rely on a digital template done by a younger colleague. We compared the accuracy of preoperative templating between orthopedic residents (group A) and an experienced orthopedic surgeon (group B). In 106 cases, the software-predicted component sizes of both groups were compared with component sizes placed surgically. An accurate prediction of the acetabular component was achieved in 63% of cases in group A compared with 88% of cases in group B (P=.001). Concerning the femoral component, accurate prediction was achieved in 89% in group A and 97% in group B (P=.021). If performed by an experienced orthopedic surgeon, digital templating is an accurate method to predict the prosthetic component size in THA. PMID- 22310398 TI - Peripheral versus central compartment starting point in hip arthroscopy for femoroacetabular impingement. AB - The purpose of this study was to compare the perioperative complications and traction times in femoroacetabular impingement hip arthroscopy with either a peripheral or central compartment starting point. Sixty patients with femoroacetabular impingement were treated with hip arthroscopy. Thirty patients had a peripheral compartment starting point and 30 had a central compartment starting point. Intra- and postoperative complications were documented along with traction times. The peripheral compartment starting group experienced 6 minor chondral injuries and 1 case of postoperative paresthesias. The central compartment starting group experienced 8 minor and 3 moderate chondral injuries, 2 labral penetrations, and 3 cases of postoperative paresthesias. Traction time averaged 46 minutes in the peripheral compartment starting group and 73 minutes in the central compartment starting group. Iatrogenic injury and traction times are decreased with peripheral vs central compartment starting in hip arthroscopy for femoroacetabular impingement. Consideration should be given for peripheral compartment starting in hip arthroscopy for the treatment of femoroacetabular impingement. PMID- 22310399 TI - Repair of medial collateral ligament injury during total knee arthoplasty. AB - Intraoperative midsubstance lacerations of the medial collateral ligament (MCL) must be addressed during surgery, and failure to obtain coronal plane stability could affect patient outcomes and satisfaction. This article reports our results of a series of patients who sustained an intraoperative MCL injury during a primary total knee arthroplasty and were treated by direct primary repair and no change in implant constraint or postoperative protocol. Over a 5-year period, 9 patients sustained this complication. We reviewed their subjective satisfaction and stability, as well as objective measures such as functional scores, physical examinations, and radiographs. Average patient age was 58 years, and mean patient body mass index was 43.3. All patients were satisfied with the procedure and demonstrated no instability on physical examination. Average Knee Society pain score was 91.5 and functional score was 73.3. No radiographic changes or signs of loosening were noted. This novel approach for intraoperative midsubstance lacerations of the MCL does not involve altering implants or postoperative protocols and has encouraging results. PMID- 22310400 TI - Kinematically versus mechanically aligned total knee arthroplasty. AB - The purpose of this study was to compare 2 alignment methods for total knee arthroplasty (TKA): kinematic alignment with the use of patient-specific guides and mechanical alignment with conventional instruments. A randomized, controlled trial of 41 kinematically aligned and 41 mechanically aligned patients was conducted with the patient, radiographic evaluator, and clinical evaluator blinded to the alignment technique. Radiographic measurements were made from long leg computer tomography scanograms. Clinical outcome scores and motion were measured preoperatively and 6 months postoperatively. The hip-knee-ankle angle (0.3 degrees difference; P=.693) and anatomic angle of the knee (0.8 degrees difference; P=.131) were similar for both groups. In the kinematically aligned group, the angle of the femoral component was 2.4 degrees more valgus (P<.000) and the angle of the tibial component was 2.3 degrees more varus (P<.000) than the mechanically aligned group. At 6 months postoperatively, the Western Ontario and McMaster Universities Osteoarthritis Index score was 16 points better (P<.000), Oxford Score was 7 points better (P=.001), combined Knee Society Score was 25 points better (P=.001), and flexion was 5.0 degrees greater (P=.043) in the kinematically aligned group than in the mechanically aligned group.Our findings suggest that the risk of early failure related to limb or knee alignment should be similar in kinematic and mechanically aligned TKA. More anatomic alignment of the implant was associated with better flexion and better clinical outcome scores in the kinematically aligned group. PMID- 22310401 TI - Effect of polyethylene component thickness on range of motion and stability in primary total knee arthroplasty. AB - Total knee arthroplasty (TKA) is a common procedure with good survivorship and functional results. Optimal results are dependent on proper osseous cuts and soft tissue balancing. Soft tissue tensioning via the polyethylene spacer thickness is an important component of soft tissue balancing. Increased thickness increases soft tissue tension and, therefore, has the potential to increase stability but decrease range of motion (ROM). Decreased polyethylene thickness may decrease soft tissue tension and has the potential to increase ROM but decrease stability. Using computer-based navigation, the intraoperative effect of increasing and decreasing polyethylene thickness in 1-mm increments on ROM and coronal stability throughout the ROM of 35 patients was examined. It was found that increasing the polyethylene thickness by 1-mm increments had a statistically significant impact on the ability to achieve full extension but had no impact on flexion. Increased polyethylene thickness decreased coronal plane motion. Coronal plane laxity increased with increased flexion irrespective of polyethylene thickness. In this patient cohort, lateral laxity became >1 degrees when the knee was flexed. However, medial structures prevented valgus angulation of >1 degrees in all scenarios except when the polyethylene was diminished by 2 mm. Changes in polyethylene thickness had an impact on the ability to gain full extension and coronal plane motion. PMID- 22310402 TI - Primary total knee arthroplasty in patients with fibromyalgia. AB - No data on the results of total knee arthroplasty (TKA) in patients with fibromyalgia have been published. The purposes of this study were to review a cohort of patients with fibromyalgia undergoing TKA to determine the level of postoperative pain and satisfaction with the surgery, the incidence of postoperative surgical complications, and revision rates and their relationship to TKA design. One hundred ten patients with fibromyalgia (141 knees) who underwent primary TKA between 1990 and 2001 were studied. The average age was 64 years (range, 39-86 years), and the average follow-up was 7 years (range, 2-16 years). Forty-five knees were cruciate retaining, and 96 had a posterior stabilized design. Clinical outcome was assessed using the Knee Society Knee Score and satisfaction regarding the results of the procedure. Postoperative surgical complications and reoperations were obtained from the registry. Sixty two patients (44%) continued with some pain after TKA. Eighty-five patients (82%) were satisfied with the results. The most common complications were arthrofibrosis and symptomatic instability. The revision rate was 6% (8 knees). Survivorship free from revision at 7 years was 89% for cruciate retaining knees and 98% for posterior stabilized knees. Patients with fibromyalgia undergoing primary TKA have a high prevalence of complications and pain. Despite continued pain, the majority of patients were satisfied with the results and reported improvements after TKA. This data should be used to counsel patients with fibromyalgia preoperatively regarding limited goals with respect to pain relief and suggests that a multimodal individualized treatment program may be necessary to achieve optimal outcomes in patients with fibromyalgia. PMID- 22310403 TI - Effect of training level on accuracy of digital templating in primary total hip and knee arthroplasty. AB - The use of digital radiography and templating software continues to become more prevalent in orthopedics as the number of total hip arthroplasty (THA) and total knee arthroplasty (TKA) procedures increases every year. The purpose of this study was to evaluate the effect of training level on the accuracy of digital templating for primary THA and TKA. Digital radiographs of 97 patients undergoing primary THA (49 cases) and TKA (48 cases) were retrospectively templated using OrthoView digital planning software (OrthoView LLC, Jacksonville, Florida). Anteroposterior hip and lateral knee radiographs were digitally templated and compared with the actual size of the implants used intraoperatively. An implant sales representative, physician assistant, medical student (J.D.K.), resident (A.R.H.), and fellowship-trained arthroplasty surgeon (B.R.L.) templated all cases independently after a standardized orientation and were blinded to the actual component sizes used for surgery. The medical student, resident, and arthroplasty surgeon retemplated the same 97 cases 1 month later to determine intraobserver reliability. Digital templating was accurate in predicting the correct implant size in 33% of THAs and 54% of TKAs. In 73% of THAs and 92% of TKAs, digital templating was within 1 size of the actual implant used, and in 88% of THAs and 99% of TKAs, templating was within 2 sizes of the final components. In no cases did the templated implant size vary by >3 sizes from the final components. Interobserver reliability for templating THAs and TKAs showed good reliability as measured by intraclass correlation coefficient (ICC) (ICC(THA)=.70; ICC(TKA)=.86). Intraobserver reliability for templating THAs had excellent reliability for the resident and arthroplasty surgeon, with a kappa coefficient (kappa) of 0.92, and good reliability for the medical student (kappa=0.78). Intraobserver reliability for templating TKAs showed excellent reliability among all examiners (kappa=0.90). PMID- 22310404 TI - Intraoperative fluid therapy and pulmonary complications. AB - The purpose of this study was to evaluate the effects of intraoperative fluid therapy on length of hospital stay and pulmonary complications in patients undergoing spine surgery. A total of 1307 patients were analyzed. Sixteen pulmonary complications were observed. Patients with a higher volume of administered crystalloids, colloids, and total intravenous fluids were more likely to have postoperative respiratory complications: the odds of postoperative respiratory complications increased by 30% with an increase of 1000 mL of crystalloid administered. The best cutoff point for total fluids was 4165 mL, with a sensitivity of 0.8125 and specificity of 0.7171, for postoperative pulmonary complications. A direct correlation existed between fluids and length of stay: patients who received >4165 mL of total fluids had an average length of stay of 3.88+/-4.66 days vs 2.3+/-3.9 days for patients who received <4165 mL of total fluids (P<.0001). This study should be considered as hypothesis-generating to design a prospective trial comparing high vs low intraoperative fluid regiments for patients undergoing spine surgery. PMID- 22310405 TI - Mid-term outcome of opening-wedge high tibial osteotomy for varus arthritic knees. AB - Gonarthrosis in the relatively young and active population causes major daily discomfort and disability. If the arthritic process is mainly limited to the medial compartment, the axis of a varus knee can be realigned laterally with high tibial osteotomy to unload the medial compartment and allow some cartilage regeneration and pain relief. This study describes the outcomes of patients who underwent opening-wedge high tibial osteotomies using Puddu plate (Arthrex, Naples, Florida) fixation. Eighteen patients (22 knees) with genu varum and medial compartment osteoarthritis were followed-up for an average of 6.3+/-2.3 years after high tibial osteotomy with Puddu plate fixation and iliac crest allograft. Clinical outcome was assessed by the Oxford Knee Score and subjective satisfaction rating. Pre- and postoperative radiographs were evaluated for tibiofemoral angle, Insall-Salvati index, and Kellgren-Lawrence Grading Scale for osteoarthritis. Mean patient age at surgery was 44+/-13.7 years, and mean body mass index was 29.1+/-4.7 kg/m(2). At last follow-up, mean Oxford Knee Score improved from 22.4+/-13.5 to 37.2+/-13.7 (P=.002). Average subjective satisfaction rate at last follow-up was 8+/-3. The measured tibiofemoral angle was corrected to an average genu valgum of 3.3 degrees +/-4.8 degrees (P=.001). No patient showed severe postoperative osteoarthritis (ie, Kellgren-Lawrence grade 4) at last follow-up. All radiographs showed full incorporation of the bone grafts. At the end of the study, 2 patients underwent total knee replacement. Opening-wedge high tibial valgus osteotomy with Puddu plate fixation can be a reliable procedure for the treatment of medial-compartment osteoarthritis of the knee associated with varus deformity. PMID- 22310406 TI - Role of autologous bone graft in the surgical treatment of atrophic nonunion of midshaft clavicular fractures. AB - A retrospective study was conducted to evaluate the role of autologous bone graft in treating atrophic nonunion of midshaft clavicle fracture with a limited contact dynamic compression plate (LC-DCP). Between 1995 and 2008, sixty cases of atrophic nonunion of midshaft clavicle fractures were managed with open reduction and internal fixation with an LC-DCP. The cases were separated into 2 groups to evaluate the effect of autologous bone graft in the enhancement of bone union. In group 1 (n=24), autologous bone graft was not used; in group 2 (n=36), autologous bone graft was used. Pre- and postoperative management were the same in both groups. Radiographic results and functional outcomes according to the Quick Disability of Arm, Shoulder, and Hand score were evaluated. Average follow-up was 25.2 months (range, 24-48 months).No statistically significant difference was found between the 2 groups regarding demography and preoperative functional scores (P>.05). Operative time and hospital stay were statistically significant longer in group 2 (P<.001), and donor site pain was apparent in group 2. All 60 patients had uneventful union. No statistically significant differences were found between the 2 groups regarding union time (average, 9.8 weeks in group 1 and 9.2 weeks in group 2) and postoperative functional scores (P>.05). Limited contact dynamic compression plate fixation is an effective method for treating atrophic nonunion of midshaft clavicle fractures. Autologous bone graft was not needed. PMID- 22310407 TI - Ulnar collateral ligament reconstruction in posttraumatic elbow release. AB - The purpose of this retrospective cohort comparison study was to determine the effect of ulnar collateral ligament reconstruction on postoperative range of motion (ROM) in patients undergoing posttraumatic elbow contracture release. Twenty-four consecutive patients underwent elbow arthrolysis. Six patients also underwent simultaneous collateral ligament excision and reconstruction, and 18 did not require ligament excision. All patients followed the same postoperative rehabilitation program. Minimum follow-up was 12 months. Final flexion/extension ROMs were similar in both groups. No subjective reports of postoperative elbow instability occurred in either group. Ligament reconstruction and early postoperative motion can be safely performed in the setting of posttraumatic elbow capsulectomy without sacrificing ROM gain or compromising stability provided by the ligament reconstruction. PMID- 22310408 TI - Does adding computed tomography change the diagnosis and treatment of Tillaux and triplane pediatric ankle fractures? AB - Computed tomography (CT) has been deemed a necessary part of management for Tillaux and triplane pediatric ankle fractures. However, no previously published study has attempted to quantify its usefulness in changing management. Six third party, blinded orthopedic surgeons (F.A.L., E.N.K., D.M.P., K.J.K., D.S.F., K.A.E.) were randomly assigned to evaluate 24 pediatric Tillaux or triplane fractures with plain radiographs; after 6 months, they were again randomly assigned to evaluate the 24 radiographs plus CT scans, totaling 144 third-party, blinded evaluations. Intra- and interobserver agreements were assessed via correlation coefficient analysis. Evaluation of CT scans changed the original diagnosis of fracture type from Tillaux to triplane fracture in 7 (4.9%) of 144 evaluations. Inter- and intraobserver agreements regarding primary treatment plans did not significantly differ between radiographs and radiographs plus CT scans (0.5 vs 0.4, respectively; P>.05). The addition of CT did not significantly change the impression of the amount of displacement per case. By adding CT, more patients who were assigned nonoperative management were reassigned to operative treatment (P=.033). Adding CT, although it may influence the decision to operate on Tillaux and triplane fractures, may not be as useful as previously thought. PMID- 22310409 TI - Surgical reconstruction of chronic achilles tendon ruptures using various methods. AB - The purpose of this study was to evaluate the surgical outcomes of reconstruction of chronic Achilles tendon ruptures using various methods, including Achilles tendon allograft. Between October 2003 and March 2010, twelve patients with chronic Achilles tendon ruptures and a defect gap of >4 cm underwent surgical reconstruction with V-Y advancement, gastrocnemius fascial turn-down flap, flexor hallucis longus tendon transfer, or Achilles tendon allograft. The study group comprised 11 men and 1 woman. At last follow-up, all patients were assessed with regard to postoperative complications, self-reported level of satisfaction, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, Achilles tendon Total Rupture Score, repetitive single-heel rises, single-leg hopping test, and ankle range of motion. The AOFAS scores increased from an average of 68.7 (range, 50-87) preoperatively to 98.0 (range, 88-100) postoperatively. All patients were able to perform 10 repetitive single-heel raises and single-leg hops at last follow-up. No patient experienced wound complications or deep infection. Seven patients were rated as excellent, 4 as good, and 1 as fair. Chronic Achilles tendon ruptures can be successfully treated by careful selection of the reconstruction method according to the length of defect gap and state of the remaining tissue. With an extensive defect, use of an Achilles tendon allograft can be a good option. PMID- 22310410 TI - Anterior versus posterior approach in the treatment of chronic thoracolumbar fractures. AB - The purpose of this study was to compare the results of anterior approach vs posterior approach in the treatment of chronic thoracolumbar fractures. A total of 36 patients with chronic thoracolumbar fractures were divided into 2 groups. Group A was treated by an anterior approach and group B was treated by a posterior approach. During the minimum 24-month follow-up period (range, 24-62 months), all patients were prospectively evaluated for clinical and radiologic outcomes. Intraoperative blood loss, operative time, operative complications, pulmonary function, Frankel scale, and American Spinal Injury Association (ASIA) motor score were used for clinical evaluation, and Cobb angle was examined for radiologic outcome. All patients in this study achieved solid fusion, with significant neurologic improvement. Operative time, perioperative blood loss, ASIA score on admission and at final follow-up, and complications of respiratory tract infection and intercostal nerve pain were not significantly different between the 2 groups (P>.05), but complications of hemopneumothorax, abdominal distension, and constipation were fewer in group B (P<.05). Postoperative pulmonary function (P<.05) and correction of posttraumatic kyphosis were better in group B (P<.05). PMID- 22310411 TI - Clinical application of a new plate fixation system in open-door laminoplasty. AB - The purpose of this retrospective clinical series was to evaluate the benefits and complications of plate fixation for open-door laminoplasty in cervical spondylotic myelopathy with multilevel spinal stenosis compared with open-door laminoplasty without fixation. Forty-nine patients underwent open-door laminoplasty for cervical myelopathy with multilevel spinal stenosis with at least 13 months of follow-up. A plate was used as the sole method of fixation between the lateral mass and lamina with 3 screws. Computed tomography scans obtained pre- and postoperatively were assessed for plate complications and spinal canal enlargement. Pre- and postoperative neurological condition was assessed by the Japanese Orthopedic Association (JOA) myelopathy score. Overall cervical spine range of motion (ROM) was measured in full flexion and extension radiographs pre- and postoperatively. No restenosis due to door reclosure was noted, and no plates failed. No screws were backed out or broken. Almost all patients showed neurological improvement. The JOA score increased by 3.9+/-0.7 points in the suture group and 4.3+/-0.8 points in the plate group (P>.05). The postoperative increase in mean anteroposterior diameter of the spinal canal from C3 to C7 was 4.5+/-0.6 mm in the suture group and 5.1+/-0.5 mm in the plate group. The greater mean anteroposterior diameter increase in the plate group was statistically significant (P<.01). The mean cervical ROM decreased in the plate and suture groups postoperatively (P<.001). No significant difference was found in mean cervical ROM reduction between the groups (P>.05). No difference in axial symptoms was found between the 2 groups. PMID- 22310412 TI - Pelvic resections. AB - The complexity of pelvic anatomy and the extent of tumor growth makes treatment of patients with primary bone sarcomas in the pelvis difficult in terms of local control. Before the 1970s, most tumors in the bony pelvis were surgically treated with hindquarter amputation. Currently, improved techniques for clinical staging, adjuvant treatments, evolutions in metallurgy, and development of new surgical techniques make limb-salvage surgery and reconstruction possible alternatives to hemipelvectomy and resection-arthrodesis. The advantages of amputation over resections at the pelvis are a lower incidence of complications, a limited area at risk for recurrence, and a faster recovery time compared with all but the most limited pelvic resections. The disadvantages, especially after periacetabular resections, are leg-length discrepancy and impaired hip and gait function. The indication for limb salvage is the ability to obtain wide margins without compromising survival and function. Although having to resect the sciatic nerve to obtain adequate margins does not always mean that an amputation should be performed, the combination of a major pelvic resection and the functional consequences of sciatic nerve resection results in an extremity usually not worth saving; loss of femoral nerve function does not result in a significant gait disturbance, especially if the hemipelvis is stable. Reconstruction options after major pelvic resections have also evolved, but they remain difficult, especially when the acetabulum is involved. PMID- 22310413 TI - Minimally invasive versus conventional dynamic hip screw for the treatment of intertrochanteric fractures in older patients. AB - The purpose of this study was to compare minimally invasive and conventional dynamic hip screw techniques for the treatment of intertrochanteric fractures in older patients. Relevant randomized, controlled studies were included. The methodological quality was assessed, and data were extracted independently. Five studies (353 fractures) that compared minimally invasive and conventional dynamic hip screw techniques were included. The rates of serious postoperative complications, operative time (minutes), hemoglobin decrease (g/dL), postoperative Harris Hip Scores, and length of stay (days) were the outcomes of interest. A lower rate of serious postoperative complications was correlated with the minimally invasive dynamic hip screw group compared with the conventional dynamic hip screw group (relative risk, 0.35; 95% confidence interval [CI], 0.16, 0.78), average operative time (weighted mean difference, -16.32; 95% CI, -28.78 to -3.86), hemoglobin decrease (weighted mean difference, -1.44; 95% CI, -1.98 to -0.89), and length of stay (weighted mean difference, -3.72; 95% CI, -5.44 to 2.01) were lower in the minimally invasive dynamic hip screw group, and the postoperative Harris Hip Score (weighted mean difference, 1.42; 95% CI, 0.23 to 2.60) was higher in the minimally invasive dynamic hip screw group. PMID- 22310414 TI - Locking plate fixation for proximal humerus fractures. AB - Locking plates are increasingly used to surgically treat proximal humerus fractures. Knowledge of the bone quality of the proximal humerus is important. Studies have shown the medial and dorsal aspects of the proximal humeral head to have the highest bone strength, and this should be exploited by fixation techniques, particularly in elderly patients with osteoporosis. The goals of surgery for proximal humeral fractures should involve minimal soft tissue dissection and achieve anatomic reduction of the head complex with sufficient stability to allow for early shoulder mobilization. This article reviews various treatment options, in particular locking plate fixation. Locking plate fixation is associated with a high complication rate, such as avascular necrosis (7.9%), screw cutout (11.6%), and revision surgery (13.7%). These complications are frequently due to the varus deformation of the humeral head. Strategic screw placement in the humeral head would minimize the possibility of loss of fracture reduction and potential hardware complications. Locking plate fixation is a good surgical option for the management of proximal humerus fractures. Complications can be avoided by using better bone stock and by careful screw placement in the humeral head. PMID- 22310415 TI - Cement-in-cement acetabular revision with a constrained tripolar component. AB - Dislocation of a total hip replacement (THR) is common following total hip arthroplasty (THA). When nonoperative management fails to maintain reduction, revision surgery is considered. The use of constrained acetabular liners has been extensively described. Complete removal of the old cement mantle during revision THA can be challenging and is associated with significant complications. Cement in-cement revision is an established technique. However, the available clinical and experimental studies focus on femoral stem revision. The purpose of this study was to present a case of cement-in-cement acetabular revision with a constrained component for recurrent dislocations and to investigate the current best evidence for this technique. This article describes the case of a 74-year old woman who underwent revision of a Charnley THR for recurrent low-energy dislocations. A tripolar constrained acetabular component was cemented over the primary cement mantle following removal of the original liner by reaming, roughening the surface, and thoroughly irrigating and drying the primary cement. Clinical and radiological results were good, with the Oxford Hip Score improving from 11 preoperatively to 24 at 6 months postoperatively. The good short-term results of this case and the current clinical and biomechanical data encourage the use of the cement-in-cement technique for acetabular revision. Careful irrigation, drying, and roughening of the primary surface are necessary. PMID- 22310416 TI - Free vascularized fibula graft to treat chondroblastoma of the hip. AB - Chondroblastomas are rare tumors that present in the epiphysis of the long bones. Bone grafting following aggressive surgical curettage has yielded the best results. When present in the femoral head, they pose a higher risk of recurrence due to the difficulty of achieving an adequate resection without destroying the structural integrity of the weight-bearing surface. This article describes a case of surgical treatment of a chondroblastoma of the femoral head with the use of a free vascularized fibula graft. A 26-year-old woman had several months of increasing left hip pain and decreased range of motion. Imaging studies confirmed a large bubbly lesion with sclerotic borders in the left femoral head consistent with chondroblastoma. After performing an aggressive and complete excisional biopsy, a large cavitary defect remained in the femoral head. Reconstruction of the defect and structural support was achieved using a free vascularized fibula. Nine years postoperatively, the patient had full hip motion, no pain, and no radiographic evidence of collapse. A free vascularized fibula graft is an excellent option for the reconstruction of a large femoral head defect after chondroblastoma resection. PMID- 22310417 TI - Hip arthroscopy: intra-articular saucerization of the acetabular cotyloid fossa. AB - Hip arthroscopy is increasingly recognized as a treatment option for patients with hip pain and labral tears. When emphasis is placed on labral tears as a primary clinical finding in the peripheral compartment, a broader view of the pathophysiology of these tears may be missed. Therefore, it is imperative to gain arthroscopic surgical access to the central compartment and determine if its contents affect the congruency of the hip joint. Abnormal bone and fibro-fatty tissue in the cotyloid fossa decrease the space available for the ligamentum teres, leading to lateral subluxation of the femoral head and rim loading of the acetabulum at the chondrolabral junction. Rim loading of the acetabulum may induce articular-sided labral tears due to hip incongruency. Although these labral tears may require refixation, the congruency of the hip joint should be restored to the best extent possible. Arthroscopic intra-articular saucerization and debridement of space-occupying lesions in the cotyloid fossa increase the space available for the ligamentum teres, improve the congruency of the hip joint, and mitigate against acetabular rim loading. This article describes a case of arthroscopic intra-articular saucerization of the cotyloid fossa in a 25-year old man with chronic hip pain. PMID- 22310418 TI - Anterior cruciate ligament reconstruction failure after tibial shaft malunion. AB - Anterior cruciate ligament (ACL) reconstruction is common, with >100,000 procedures performed each year in the United States. Several factors are associated with failure, including poor surgical technique, graft incorporation failure, overly aggressive rehabilitation, and trauma. Tibial shaft fracture is also common and frequently requires operative intervention. Failure to reestablish the anatomic alignment of the tibia may cause abnormal forces across adjacent joints, which can cause degenerative joint disease or attritional failure of the surrounding soft tissues. This article describes a case of ACL reconstruction failure after a tibial fracture that resulted in malunion. Excessive force across the graft from lower-extremity malalignment and improper tunnel placement likely contributed to the attritional failure of the graft. This patient required a staged procedure for corrective tibial osteotomy followed by revision ACL reconstruction. This article describes ACL reconstruction failure, tibial shaft malunions, their respective treatments, the technical details of each procedure, and the technical aspects that must be considered when these procedures are done in a staged manner by 2 surgeons. PMID- 22310419 TI - Patellar polyethylene spinout after low-contact stress, high-congruity, mobile bearing patellofemoral arthroplasty. AB - A low-contact stress, high-congruity, mobile-bearing patellofemoral joint arthroplasty decreases the contact force in the patellofemoral joint, theoretically reducing patellar polyethylene wear and increasing implant longevity. This article describes the case of a 47-year-old obese woman who presented with pain and loss of extension after a low-contact stress, high congruity, mobile-bearing patellofemoral joint arthroplasty. Radiographs revealed dislocation (ie, spinout) of the patellar polyethylene. Patellar polyethylene spinout is a rare complication of metal-backed, mobile-bearing patellar resurfacing. Theoretically, patellar polyethylene spinout in low-contact stress, high-congruity, mobile-bearing patellofemoral arthroplasty is related to implant design and the placement of the metal base plate. Ultimately, the articulation of low-contact stress, high-congruity, mobile-bearing patellofemoral arthroplasty may be too congruent to resist the forces of the patellofemoral joint, particularly in patients who are obese, and the patellar rotation allowed by this articulation may not be sufficient for all patients. Should patellar spinout occur, replacement of the polyethylene is not sufficient to correct the problem; hence, revision of the patellar and trochlear components is required because it remains unclear whether failure is secondary to patellar or trochlear design deficiencies. PMID- 22310420 TI - Recurrent, locked posterior glenohumeral dislocation requiring hemiarthroplasty and posterior bone block with humeral head autograft. AB - This article describes the case of a 77-year-old man with a recurrent posterior shoulder dislocation, treated with humeral hemiarthroplasty and reconstruction of a large posteroinferior glenoid defect with a bone block created from humeral head autograft. On examination, the patient's left arm was held in internal rotation against his stomach, with minimal swelling about the deltoid. His shoulder was nontender to palpation; however, he had substantial motion restrictions, and attempted motion was painful. He could forward elevate to 30 degrees , extend to 0 degrees , internally rotate to belly, and passive external rotation was limited to -30 degrees . He maintained full elbow, wrist, and hand range of motion, and his neurovascular examination was intact. Radiographs revealed a recurrent posterior glenohumeral dislocation, with a large reverse Hill-Sachs defect involving the lesser turberosity and humeral head. Computed tomography with 3-D reconstruction revealed the humeral head defect involving the lesser tuberosity and approximately 40% of the humeral head and a large comminuted posteroinferior glenoid fracture measuring 2.7*0.8 cm, encompassing approximately 30% of the posteroinferior glenoid surface. Standard fixation was not possible; therefore, the resected humeral head was fashioned into an elliptical piece mirroring the size of the defect of the posteroinferior glenoid. Rough measurements of the defect were made and marked on the humeral head, which was then cut with an oscillating saw to approximate the size and shape of the defect. The glenoid graft provided an extension to the glenoid and prevented posterior subluxation with no block to motion. One year postoperatively, he had full strength (5/5) with external rotation, forward elevation, and internal rotation, 140 degrees of active forward elevation, 30 degrees of external rotation, internal rotation to T7, and no episodes of instability. To our knowledge. this is the first report of this technique in the literature. It is an alternative to total shoulder arthroplasty. PMID- 22310421 TI - Progressive osteolysis and surface chondrolysis of the proximal humerus following influenza vaccination. AB - Influenza vaccination is a common annual event among individuals in the United States. Complications, although infrequent, are usually mild and self-limiting. This article describes the case of a 46-year-old man who experienced progressive osteolysis and surface chondrolysis of the proximal humerus following routine influenza vaccination. The patient presented with shoulder pain and limited range of motion 3 weeks following vaccination in the deltoid area. No skin changes were noted, inflammatory markers were normal, and the patient's pain and disability persisted despite nonsteroidal anti-inflammatory drugs and occupational therapy. Plain radiographs revealed a small lytic area involving the greater tuberosity of the humeral head. Magnetic resonance imaging (MRI) showed abnormal uptake and cystic changes involving the greater tuberosity of the humeral head; repeat MRI at 5 months showed progression in the cystic changes. Diagnostic arthroscopy of the shoulder revealed a hyperemic joint capsule and extensive, full-thickness chondrolysis of the humeral head. Cystic biopsy demonstrated inflammatory cells and granulation tissue, consistent with foreign body response. Cultures were negative. Surgical debridement of the cystic areas and resurfacing of the humeral head yielded a good outcome. To our knowledge, this is the first reported complication of influenza vaccination requiring surgical intervention. Physicians need to be aware of the potential for osteolysis and chondrolysis, which may require aggressive forms of management. PMID- 22310422 TI - Iatrogenic subclavian arteriovenous fistula: rare complication of plate osteosynthesis of clavicle fracture. AB - Iatrogenic subclavian arteriovenous fistula is rare and has not been reported as a complication of plate osteosynthesis of clavicle fracture. This article describes the first case of iatrogenic subclavian arteriovenous fistula caused by plate osteosynthesis. A 36-year-old man sustained a right middle clavicle fracture in an injury and underwent open reduction and internal fixation with clavicular compression plate 3 days later in a local hospital. On the second postoperative day, a pulsatile mass and thrill were detected at the right supraclavicular region. The patient was discharged 3 days postoperatively with no extra inspection. Three months later, he was admitted to our institution because the mass was getting bigger and weakness was felt in his right upper limb. Digital subtraction angiography confirmed a subclavian arteriovenous fistula. Vascular surgeons treated the patient successfully using endovascular techniques. The subclavian arteriovenous fistula was eliminated with a fully expanded stent graft, and the plate was removed simultaneously. The result was satisfactory, and the postoperative course was uneventful. This case demonstrated that subclavian arteriovenous fistula could be an iatrogenic complication of screw-and-plate osteosynthesis of clavicle fracture. The operative manipulation in the process of fracture reduction and hole drilling should be meticulous, and the screw length must be accurate. Orthopedic surgeons should be aware of this uncommon complication with plate osteosynthesis of clavicle fracture. We recommend using an endovascular surgical technique for treatment of this complication. PMID- 22310423 TI - Minimally invasive plate osteosynthesis for metastatic pathologic humeral fractures. AB - Because patients with metastatic bone disease may survive only 3 to 12 months, the goal of surgery for pathologic fractures is to attain rigid and durable internal fixation and immediate postoperative use of the upper extremity. Surgical options such as intramedullary nailing, plating, and insertion of prosthesis usually reinforced with bone cement have been proposed for pathological humeral fractures. We describe a 42-year-old man with a pathologic distal humeral fracture. The fracture location and lack of distal bone stock precluded the use of intramedullary nails. We performed minimally invasive plating by using a locking plate for bridging and stabilization of fracture. Minimally invasive plate osteosynthesis of the humeral shaft was developed to allow anterior plate and screw stabilization involving less soft tissue disruption and to theoretically improve healing rates and reduce complications, such as infection and iatrogenic radial nerve palsy. Plain radiographs showed stable consolidation of the fracture without screw loosening at the 7-month follow-up. Elbow range of motion was 120 degrees , and the arm was stable without pain. Minimally invasive plate using a locking plate can provide stable fixation and allow early arm mobilization without protection and decrease the risk of operation-related complications, making it a useful surgical alternative in the treatment of pathologic humeral fractures. PMID- 22310424 TI - Aberrant iliac artery: far lateral lumbosacral surgical anatomy. AB - A 44-year-old man presented after 3 weeks of progressively worsening atraumatic onset pain in the right anteromedial thigh. The pain was sharp and radiated to the anteromedial shin and medial foot. The patient had no associated weakness, numbness, or bowel/bladder dysfunction. Nonsteroidal anti-inflammatory, pain, and neuropathic-relieving drugs had limited effect. He underwent interlaminar injections, which provided transient relief of his shin symptoms. After conservative management failed, a spine surgeon (not affiliated with our practice) recommended an anterior lumbar interbody fusion via far lateral approach. The patient presented to our spine clinic for a second opinion. Closed magnetic resonance imaging revealed an aberrant iliac artery impinging on the lumbar plexus and a foraminal herniation at L4-L5 on the right, an orientation more lateral than expected or seen on the contralateral side. We recommended physical therapy that focused on core strength and adequate stretching prior to considering surgery. The patient's symptoms have since resolved. Common iliac artery anomalies are rare. No known incidence exists. The finding in this case was incidental and, if missed, could have led to vascular compromise. To prevent such an injury during minimally invasive (transpsoas lateral approach) spine surgery, we recommend careful examination of radiographs for aberrant vessels. PMID- 22310425 TI - Ossification of the posterior longitudinal and yellow ligaments on the lumbar spine. AB - Ossification of the posterior longitudinal ligament and ossification of the yellow ligament are the main causes of spinal canal stenosis. This article describes a case of ossification of the posterior longitudinal and yellow ligaments on the lumbar spine. The patient presented with gradually worsening left lower-extremity ache and pain. The deep tendon reflex was hyperreflexia in the lower extremities. Disturbances existed in the blade and bowel. The ossified lesion of ossification of the posterior longitudinal ligament was observed at L5 S1, and plain lateral radiographs and computed tomography revealed ossification of the yellow ligament on L3, which occupied a large part of the spinal canal. Because of the findings on the preoperative radiographs, we performed posterior approach decompression and bone grafting and excisied the ossified lesion. Pedicle screws were inserted from L3 to S1. The patient's symptoms disappeared postoperatively, and his Japanese Orthopaedic Association score was 25 two weeks postoperatively. No standard surgical procedure exists for the treatment of lumbar ossification of the posterior longitudinal ligament, but it is important to select a surgical procedure according to individual patient conditions. Many factors, such as local mechanic stress, tissue metabolism, high glucose, and genetics, contribute to the progression of ossification of the posterior longitudinal and yellow ligaments on the lumbar spine. However, the mechanism is unclear. Further study and long-term follow-up on lumbar ossification of the posterior longitudinal ligament is needed. PMID- 22310426 TI - WSU Medical School -- a study in innovation and resilience. PMID- 22310428 TI - The fast neutron therapy programme for patients in South Africa should come to an end. PMID- 22310429 TI - Akhenaten, a unique pharaoh. PMID- 22310430 TI - Cataract surgery rates. PMID- 22310431 TI - Electrolyte supplementation drinking and renal failure. PMID- 22310432 TI - Recommendations pertaining to the use of viral vaccines: influenza 2012. PMID- 22310433 TI - Embolic stroke from common carotid pseudo-aneurysm. PMID- 22310436 TI - How times have changed: HIV and AIDS in South Africa in 2011. PMID- 22310437 TI - PHC re-engineering may relieve overburdened tertiary hospitals in South Africa. AB - Under the National Health Insurance, a hospital is expected to provide service to patients based on its category. However, in reality the tertiary hospitals offer every level of care, resulting in poor quality of care and over-expenditure. The Polokwane/Mankweng Hospital Complex is a provincial tertiary hospital that delivers tertiary care as well as dealing with some secondary and primary care cases. This study evaluated the hospital casualty department in the Polokwane/Mankweng Hospital Complex. A sample of 250 patients' records was selected by simple random sampling from a cohort of 14 113 patients who attended the Polokwane Hospital Casualty Department during the 1-year study period. Most patients were admitted in the casualty department as a result of injuries (25%). Only 20% (N=51) of the patients were referred from other health facilities. Half of the patients could have been managed at a regional or district hospital. The overall expenditure for the casualty unit during the 1-year study period was R10 321 401.42 and the combined unit cost was estimated at R731.34 per single emergency care patient excluding the capital costs. Referral systems must be strengthened to manage patients at regional and district level to reduce the burden on the Polokwane/Mankweng Hospital Complex. It is hoped that the Primary Health Care (PHC) Re-engineering Policy will address this by strengthening the referral system in PHC facilities. PMID- 22310438 TI - Progress of preventing mother-to-child transmission of HIV at primary healthcare facilities and district hospitals in three South African provinces. AB - Improving national prevention of mother-to-child (PMTCT) services in South Africa has been challenging. PMTCT outcomes were analysed at 58 primary and secondary level antenatal facilities across seven high HIV-burden sub-districts in three provinces, over an 18 month period during which new South African PMTCT clinical guidelines were implemented and a nurse quality mentor program was expanded. Early infant HIV DNA polymerase chain reaction test positivity reduced by 75.2% from 9.7% (CI: 8.1%-11.5%) to 2.4% (CI: 1.9%-3.1%); p<0.0005. HIV test positivity at 18 months of age decreased by 64.5% from 10.7% (CI: 7.2-15.1%) to 3.8% (CI: 2.4-5.6%); p<0.0005. PMTCT outcomes have improved substantially at these facilities. PMID- 22310439 TI - DVT prophylaxis in relation to patient risk profiling - TUNE-IN study. AB - BACKGROUND: Patients in acute hospital care show a high risk for venous thromboembolism (VTE); 52% of patients globally are at risk, with approximately only half receiving appropriate prophylaxis. OBJECTIVES: The TUNE-IN study's primary objective was to evaluate the use of VTE prophylaxis in the private sector in South Africa in hospitalised patients in relation to patient risk profile, via both a clinical assessment and utilising a modified risk assessment model (RAM). The secondary objective was to evaluate the relationship between prophylaxis and the level of mobility at discharge as well as on days 3, 7 and 14 post discharge. RESULTS: Of the 608 patients enrolled, 54.1% were evaluated to be at risk for VTE clinically whilst, with RAM assessment, 74.6% were assessed at risk. Adequate prophylaxis was given to only 70.9% of all patients. CONCLUSION: Data appear to correlate with global findings (ENDORSE study): more than 50% of hospitalised patients are at risk for VTE. Clinical risk assessment does not correlate with RAM utilisation, resulting in possible over-diagnosis of VTE risk in low- and moderate-risk patients, with the converse happening in high- and highest-risk patients. Certain risk groups are easily defined for VTE risk (e.g. major orthopaedic surgery), but individual risk assessment is crucial as it often reveals underlying and overlooked risk factors, with BMI and age the most frequently overlooked risk factors. PMID- 22310440 TI - Sudden and unexpected deaths in an adult population, Cape Town, South Africa, 2001-2005. AB - BACKGROUND: According to the regulations of the National Health Act, all 'sudden and unexpected' deaths in South Africa should be referred to Forensic Pathology Services (FPS) for further investigation. OBJECTIVES: We aimed to determine the final outcomes of forensic postmortem examinations in 'sudden and unexpected' adult deaths referred to Tygerberg FPS between 2001 and 2005. METHODS: The study was a retrospective descriptive study. Demographic and autopsy data from adult cases of 'sudden and unexpected deaths' referred to Tygerberg FPS were collected and analysed. Results. Some 816 adult cases of 'sudden' deaths were studied. The presumed manner of death was natural in 645 (79.0%) cases, unnatural in 99 (12.2%), and undetermined in 72 (8.8%). Diseases of the cardiovascular, respiratory and central nervous systems accounted for the majority of natural deaths. Infectious diseases accounted for most deaths in the youngest age group studied (18 - 29 years); however, ischaemic heart disease was the most prevalent cause of death in the total study population. CONCLUSIONS: This study highlighted the lack of useful pre-autopsy information and therefore the performance of 'unnecessary' medicolegal autopsies in a resource-limited country. Clinicians could ease the burden by giving useful information when referring cases to FPS. Feedback should be given to family members, especially where the cause of death may have an impact on surviving family members. PMID- 22310441 TI - Persistent failure of the COIDA system to compensate occupational disease in South Africa. AB - Cases of occupational disease, solvent encephalopathy and occupational asthma are used to exemplify failings of the workers' compensation system in South Africa, that include delays in processing claims, non-response to requests for information, and inadequate assessment of disability. These and other systemic deficiencies in administration of the Compensation for Occupational Injuries and Diseases Act of 1993 (COIDA) reduce access by workers with occupational disease to private medical care, and shift costs to workers and to public sector medical care. Another unintended effect is to promote underreporting of occupational disease by employers and medical practitioners. Reforms have been tried or proposed over the years, including decentralisation of medical assessment to specialised units, which showed promise but were closed. Improved annual performance reporting by the Compensation Commissioner on the processing of occupational disease claims would promote greater public accountability. Given the perennial failings of the system, a debate on outsourcing or partial privatisation of COIDA's functions is due. PMID- 22310442 TI - Nurse-initiation and maintenance of patients on antiretroviral therapy: are nurses in primary care clinics initiating ART after attending NIMART training? AB - OBJECTIVES: To determine the percentage of nurses initiating new HIV-positive patients on therapy within 2 months of attending the Nurse Initiation and Maintenance of Antiretroviral Therapy(NIMART) course, and to identify possible barriers to nurse initiation. METHODS: A brief telephonic interview using a structured questionnaire of a randomly selected sample (126/1736) of primary care nurses who had attended the NIMART course facilitated by the Foundation for Professional Development (FPD) between October 2010 and 31 March 2011 at primary care clinics in 7 provinces. Outcome measures were the number of nurses initiating ART within 2 months of attending the FPD-facilitated NIMART course. RESULTS: Of the nurses surveyed, 62% (79/126) had started initiating new adult patients on ART, but only 7% (9/126) were initiating ART in children. The main barrier to initiation was allocation to other tasks in the clinic as a result of staff shortages. CONCLUSIONS: Despite numerous challenges, many primary care nurses working in the 7 provinces surveyed have taken on the responsibility of sharing the task of initiating HIV-positive patients on ART. The barriers preventing more nurses initiating ART include the shortage of primary care nurses and the lack of sufficient consulting rooms. Expanding clinical mentoring and further training in clinical skills and pharmacology would assist in reaching the target of initiating a further 1.2 million HIV-positive patients on ART by 2012. PMID- 22310443 TI - Text messages as a learning tool for midwives. AB - The use of cell phone text messaging to improve access to continuing healthcare education in under-resourced settings is not well documented. We aimed to assess whether this method of education is acceptable to South African midwives in both the public and private sectors. Essential healthcare lessons from the Maternal Care book of the Perinatal Education Programme (PEP) were delivered via text message to more than 2 500 midwives each week for a period of 6 months. Each message concluded with a link to a website, where additional information about each lesson could be accessed. Results of a survey, conducted with 50 of the message recipients, demonstrated that the text messages were well received by the midwives; the information was widely shared with colleagues and was believed to improve learning and patient care. Lack of access to the internet, or failure to utilise this facility to obtain additional information, indicated that limitations still exist in internet-based distance education, especially in the public sector. The use of text messaging promises to provide cost-effective learning opportunities, and improve a wide range of clinical services, such as the management of HIV-infected children and adults. PMID- 22310444 TI - Comparative MIC evaluation of a generic ceftriaxone by broth microdilution on clinically relevant isolates from an academic hospital complex in South Africa. AB - We evaluated the in vitro microbiological efficacy of a generic ceftriaxone product against several clinically significant organisms collected from sterile sites. The minimum inhibitory concentration (MIC) of each was determined simultaneously with the reference and the generic ceftriaxone product. Comparative analysis of MICs between the two products for each isolate was performed using both categorical (interpretive) agreement and essential (actual MIC value) agreement. A total of 260 isolates were tested. Overall, there was categorical agreement of 98.9% and essential agreement of 95.8%. The categorical agreement for all isolates (96.7 - 100%) accorded with international standards, as no very major errors were seen and the major error rate was less than 3%. Of the 90 isolates of E. coli (40), Klebsiella spp. (40) and Salmonella spp. (10), 87.6% had an MIC less than or equal to 0.12mg/l. The generic ceftriaxone product showed equivalent efficacy by MIC determination to the reference formulation. Ceftriaxone remains a viable and useful antimicrobial agent against a variety of clinically relevant organisms in our setting. PMID- 22310445 TI - Management guidelines for acute infective diarrhoea / gastroenteritis in infants. AB - BACKGROUND: Acute onset vomiting and diarrhoea is one of the most common illnesses of infancy, and is second only to respiratory illnesses as a cause of childhood deaths worldwide. Existing guidelines for management of diarrhoea are often ignored in public and private practice, possibly because of a perception that the guidelines are too simple, or because of expectations of the need to give 'real' drug therapy to stop diarrhoea. OBJECTIVES: This guideline provides a problem-based approach to the basics of present-day management of acute gastroenteritis, and discusses the evidence for the recommendations. Recommendations. Each episode of diarrhoea must be seen as an opportunity for caregiver education in the prevention of the illness, in the 'what' and 'how' of oral rehydration and re-feeding, and in the recognition of when to seek help. The vast majority of patients recover rapidly, but serious complications do occur, and must be recognised and managed correctly. Validation. The guidelines are endorsed by the Paediatric Management Group (PMG) in South Africa. CONCLUSION: The aim of management is to help the child to maintain or regain hydration, and to recover from diarrhoea, with careful attention to adequate oral rehydration and judicious re-feeding. PMID- 22310446 TI - A dance of empowerment - lessons for the NHI? PMID- 22310447 TI - Dismal use of legal safety net for mental health patients. PMID- 22310448 TI - Dual-frequency (20/40 kHz) ultrasonic assisted photocatalysis for degradation of methylene blue effluent: synergistic effect and kinetic study. AB - Dual-frequency ultrasonic assisted photocatalysis (DUAP) was proposed to enhance the degradation efficiency of methylene blue (MB) solution. The influence of operational parameters, i.e., irradiation time, ultrasonic arrangement, TiO(2) concentration and power density, was studied. The results implied that the rapid degradation of MB solution was achieved in 18 min under DUAP with the dual frequencies of 20/40 kHz. Kinetic investigation of MB degradation for the DUAP process was conducted on the basis of first-order kinetic equation and the synergistic effect was assessed by examination of the apparent rate constant. The effect of ultrasonic arrangement was analyzed by comparison of the pressure amplitude of ultrasonic superposition field. The evolvement of intermediate products and the role of active species during DUAP were distinguished by UV-Vis spectra and the free radical scavenging experiment. PMID- 22310449 TI - Imaging and manipulation of the Si(100) surface by small-amplitude NC-AFM at zero and very low applied bias. AB - We use a noncontact atomic force microscope in the qPlus configuration to investigate the structure and influence of defects on the Si(100) surface. By applying millivolt biases, simultaneous tunnel current data is acquired, providing information about the electronic properties of the surface at biases often inaccessible during conventional STM imaging, and highlighting the difference between the contrast observed in NC-AFM and tunnel current images. We also show how NC-AFM (in the absence of tunnel current) can be used to manipulate both the clean c(4 * 2) surface and dopant-related defects. PMID- 22310450 TI - Tandem post-synthetic modification for functionalized metal-organic frameworks via epoxidation and subsequent epoxide ring-opening. AB - A sequence of two new post-synthetic modifications, epoxidation using dimethyldioxirane and subsequent epoxide ring-opening, was developed, maintaining the MOF network. A kinetic study shows that the functionalization of metal organic frameworks with synthetically versatile and reactive oxirane groups is even possible for small pore diameters. PMID- 22310451 TI - Chiari III malformation. PMID- 22310452 TI - A developmental change of the visual behavior of the face recognition in the early infancy. AB - The purpose of this study was to examine developmental changes in visuocognitive function, particularly face recognition, in early infancy. In this study, we measured eye movement in healthy infants with a preference gaze problem, particularly eye movement between two face stimulations. We used the eye tracker system (Tobii1750, Tobii Technologies, Sweden) to measure eye movement in infants. Subjects were 17 3-month-old infants and 16 4-month-old infants. The subjects looked two types of face stimulation (upright face/scrambled face) at the same time and we measured their visual behavior (preference/looking/eye movement). Our results showed that 4-month-old infants looked at an upright face longer than 3-month infants, and exploratory behavior while comparing two face stimulations significantly increased. In this study, 4-month-old infants showed a preference towards an upright face. The numbers of eye movements between two face stimuli significantly increased in 4-month-old infants. These results suggest that eye movements may be an important index in face cognitive function during early infancy. PMID- 22310453 TI - Prevalence and anatomic topography of mandibular tori: computed tomographic analysis. AB - PURPOSE: Mandibular tori are located above the mylohyoid ridge. These features are relatively common in most populations, but their prevalence varies with race. The purpose of this study was to identify the prevalence and features of mandibular tori in a Korean population using computed tomographic (CT) images. MATERIALS AND METHODS: The CT images of 726 patients were analyzed in this study. The presence or absence of a mandibular torus was identified on the CT images of each patient's quadrants and categorized according to gender and age. The most common location was also evaluated according to the corresponding teeth. The cortical thickness of each torus was evaluated using a 3-dimensional reconstruction software program. RESULTS: The prevalence of mandibular tori in the entire sample was 24.1%, and most cases were bilateral. Mandibular tori were observed more frequently in young adults, with the prevalence being inversely related to age. The most frequently observed location was the premolar region, and the mean cortical thickness was 6.9 mm. CONCLUSIONS: Mandibular tori seem to change with aging. The prevalence in the present sample composed of Koreans was 24.1%, and younger patients may be more likely to develop a mandibular torus. Most tori presented a medium size bilaterally in the lingual aspect of the premolar region, and all were composed of cortical bone. PMID- 22310454 TI - Recovery of emotional smiling function in free-flap facial reanimation. AB - PURPOSE: Long-standing unilateral facial palsy is treated primarily with free flap surgery using the masseteric or contralateral facial nerve as a motor source. The use of a gracilis muscle flap innervated by the masseteric nerve restores the smiling function, without obtaining spontaneity. Because emotional smiling is an important factor in facial reanimation, the facial nerve must serve as the motor source to achieve this fundamental target. MATERIALS AND METHODS: From October 1998 to October 2009, 50 patients affected by long-standing unilateral facial paralysis underwent single-stage free-flap reanimation procedures to recover smiling function. A latissimus dorsi flap innervated by the contralateral facial nerve was transplanted in 40 patients, and a gracilis muscle flap innervated by the masseteric nerve in 10 patients. All patients underwent a clinical examination that analyzed voluntary and spontaneous smiling. RESULTS: All patients who received a latissimus dorsi flap innervated by the contralateral facial nerve and recovered muscle function (92.5%) showed voluntary and spontaneous smiling abilities. All patients who received a gracilis free flap innervated by the masseteric nerve recovered function, but only 1 (10%) showed occasional spontaneous flap activation. During those rare activations, much less movement was visible on the operated side than when the patient was asked to smile voluntarily. CONCLUSIONS: The masseteric nerve is a powerful motor source that guarantees free voluntary gracilis muscle activation; however, it does not guarantee any spontaneous smiling. Single-stage procedures that use a latissimus dorsi flap innervated by the contralateral facial nerve have a lower success rate and obtain less movement; however, spontaneous smiling is always observed. PMID- 22310455 TI - "Gigantiform" peripheral ossifying fibroma: report of a case. PMID- 22310456 TI - Influence of lower third molar anatomic position on postoperative inflammatory complications. AB - PURPOSE: Postoperative inflammatory conditions, including alveolar osteitis, surgical site infections, and abscess, are frequent complications after surgical removal of impacted mandibular third molars and multiple associated risk factors have been identified. However, few studies have evaluated the influence of extraction difficulty according to anatomic variables on postoperative inflammatory complications. PATIENTS AND METHODS: A retrospective study was performed of 585 surgically removed lower third molars. All molars were classified by a difficulty score (range 3 to 10) according to the anatomic parameters. RESULTS: For 109 third molars (19%), the extraction difficulty was rated noncomplex (score 3 to 4); for 341 (58%), moderate (score 5 to 7); and for 135 (23%), difficult (score 8 to 10). Molars rated as moderate or difficult for extraction were more often accompanied by postoperative infection than molars rated noncomplex (odds ratio 5.3 and 3.9, respectively, P < .0001). CONCLUSIONS: The results from the present study revealed a highly significant correlation between the level of difficulty for surgical removal of lower third molars (predicted by the anatomic variables) and postoperative inflammatory complications. PMID- 22310457 TI - Surgical ciliated cysts may mimic radicular cysts or residual cysts of maxilla: report of 3 cases. PMID- 22310458 TI - Low molecular weight heparin gels, based on nanoparticles, for topical delivery. AB - A commercial suspension of nanoparticles (Eudragit RS 30D) was used to manufacture a gel for topical application. Gels were prepared by mixing a polycationic polymer (Eudragit((r)) RS 30D) and a low molecular weight heparin (LMWH), an antithrombotic agent. Gels formed spontaneously at a ratio of 1:1 as a result of electrostatic interactions between the polyanionic drug and the polycationic polymer. Different types of heparin were used: Bemiparin, Enoxaparin (Lovenox), Nadroparin (Fraxiparin) and Tinzaparin (Innohep). Several LMWH concentrations were tested. Rheological measurements were performed to investigate the gel behavior. Gel formation was confirmed by dynamic rheological measurements as the elastic modulus (G') was higher than the viscous one (G"). The amount of heparin incorporated into the gel matrix was determined. A maximum of incorporation (100%) was reached using a heparin solution of 600 IU/mL. The release kinetics of LMWH from the gel were also studied. Regardless of the LMWH used in the formulation, a biphasic release profile was observed. Accordingly, a burst effect was observed. Afterwards, the release rate became steady. The penetration of the LMWH through the dermal barrier was also investigated. PMID- 22310459 TI - Physico-chemical characteristics of methotrexate-entrapped oleic acid-containing deformable liposomes for in vitro transepidermal delivery targeting psoriasis treatment. AB - This study aimed to investigate the physico-chemical characteristics and in vitro permeability of methotrexate (MTX)-entrapped deformable liposomes prepared from phosphatidylcholine (PC) and oleic acid (OA), comparing with those of MTX entrapped conventional liposomes prepared from PC and cholesterol (CH). Two formulations of MTX-entrapped PC2:CH1 and PC9:CH1 liposomes and one formulation of MTX-entrapped PC2.5:OA1 liposomes were prepared. The size, size distribution, zeta potential, thermal properties, entrapment efficiency, stability, and in vitro permeability across a porcine skin of the MTX-entrapped liposomes were evaluated. All liposome formulations showed a narrow size distribution with the size range of 80-140 nm which is appropriate for the skin permeability. The percentage of MTX loading, entrapment efficiency and the stability of MTX entrapped PC2:CH1 and PC9:CH1 liposomes were slightly higher than those of MTX entrapped PC2.5:OA1 liposomes. However, the MTX-entrapped PC2.5:OA1 liposomes enhanced the skin permeability characterized by the higher concentration and flux of MTX diffused across or accumulated in the epidermis and dermis layers of porcine skin. The enhanced permeability of MTX-entrapped PC2.5:OA1 liposomes was explained by 2 mechanisms: (1) the deformable and elasticity characteristics of OA-containing liposomes and (2) a property as a skin penetration enhancer of OA. This suggested that the PC2.5:OA1 deformable liposome was one of promising candidates to enhance the permeability of MTX for the treatment of psoriasis. PMID- 22310460 TI - Influence of acylation on the adsorption of GLP-2 to hydrophobic surfaces. AB - Acylation of proteins with a fatty acid chain has proven useful for prolonging the plasma half-lives of proteins. In formulation of acylated protein drugs, knowledge about the effect of acylation with fatty acids on the adsorption behaviour of proteins at interfaces will be valuable. The aim of this work was to study the effect of acylation on the adsorption of GLP-2 from aqueous solution to a hydrophobic surface by comparing the adsorption of the 3766 Da GLP-2 with that of a GLP-2 variant acylated with a 16-carbon fatty acid chain through a beta alanine linker. Adsorption of GLP-2 and acylated GLP-2 were studied with isothermal titration calorimetry, fixed-angle optical reflectometry and total internal reflection fluorescence. Furthermore, the effect of acylation of GLP-2 on the secondary structure was studied with Far-UV CD. Acylation was observed to have several effects on the adsorption of GLP-2. Acylation increased the amount of GLP-2 adsorbing per unit surface area and decreased the initial adsorption rate of GLP-2. Finally, acylation increased the strength of the adsorption, as judged by the lower fraction desorbing upon rinsing with buffer. PMID- 22310461 TI - Effect of polyamidoamine dendrimer G3 and G4 on skin permeation of 8 methoxypsoralene--in vivo study. AB - In the present study we have assessed the ability of (PAMAM) dendrimers G3 and G4 to facilitate transdermal delivery of 8-methoxypsoralen (8-MOP) in vivo. In vitro study using Franz diffusion cell revealed an enhanced transdermal flux for 8-MOP in complex with G3 and G4 dendrimer in relation to standard 8-MOP solution. In present study in vivo skin permeation potential of 8-MOP complex with G3 and G4 PAMAM dendrimer was assessed using confocal laser scanning microscopy (CLSM), which revealed an enhanced permeation of the 8-MOP to the deeper layers of the skin and significantly higher concentration in comparison with standard 8-MOP solution. Skin tissue 8-MOP concentration, evaluated by HPLC indicates that G3 and G4 PAMAM application significantly increase 8-MOP skin deposition in comparison with standard 8-MOP solutions after 1 and 2h. G4 appeared to be a more effective 8-MOP penetration enhancer than G3 PAMAM. Our results suggest the feasibility of G3 and G4 PAMAM dendrimers for transdermal delivery of 8-MOP resulting in better skin permeation and higher concentration of 8-MOP in epidermis and dermis of the drug that could help to improve effectiveness and safety of PUVA therapy. PMID- 22310462 TI - Introduction of diffusing wave spectroscopy to study self-emulsifying drug delivery systems with respect to liquid filling of capsules. AB - The rheology of self-emulsifying drug delivery systems (SEDDS) is not thoroughly characterized these days. Since mechanical rheometers are often not well suited to study this kind of systems, there is need for novel physical methods. Several new optical techniques based on microrheology have recently made significant progress. We apply for the first time a specific microrheological technique called diffusing wave spectroscopy (DWS) to study different SEDDS. The obtained data were then correlated with the dosing precision of automated capsule filling. As a result, the dynamic viscosities obtained from microrheology were in accordance with data from capillary viscosimetry. The DWS measurements revealed that all formulations had a clearly measurable storage modulus at frequencies >200 rad/s. Thus, all samples were low-viscous, while exhibiting non-Newtonian flow behavior. Obtained values of storage and loss modulus were then successfully correlated with the weight variability of capsules that were filled on a machine. In conclusion, the DWS technique enabled rheological analysis of self-emulsifying systems in a broad frequency range. The good data correlation with a capsule quality attribute was especially promising, since microrheological techniques are typically contact-free. Thus, they have a high potential in a quality by design framework of formulation development and production. PMID- 22310463 TI - Novel superparamagnetic iron oxide nanoparticles for tumor embolization application: preparation, characterization and double targeting. AB - The goal of this study was to develop novel embolic nanoparticles for targeted tumor therapy with dual targeting: magnetic field-guided and peptide-directed targeting. The embolic nanoparticles SP5.2/tTF-OCMCs-SPIO-NPs were prepared by surface-modifying of superparamagnetic iron oxide nanoparticles (SPIO-NPs) with o carboxymethylchitosans (OCMCs) and SP5.2/tTF (SP5.2: a peptide binding to VEGFR 1; tTF: truncated tissue factor) to improve their stability and to target over expressing VEGFR-1 cells. The physicochemical characterization results showed that the OCMCs-SPIO-NPs have a spherical or ellipsoidal morphology with an average diameter of 10-20 nm. And they possess magnetism with a saturation magnetization of 66.1 emu/g, negligible coercivity and remanence at room temperature. In addition, the confocal microscopy, Prussian blue staining and FX activation analysis respectively demonstrated the peptide-directed targeting, magnetic field-guided targeted and blood coagulation activity of the SP5.2/tTF OCMCs-SPIO-NPs. These properties separately belong to SP5.2, Fe(3)O(4) and tTF moieties of the SP5.2/tTF-OCMCs-SPIO-NPs. Thus these SP5.2/tTF-OCMCs-SPIO-NPs with double-targeting function should have a potential application in embolization therapy of tumor blood vessels. PMID- 22310464 TI - Two dimensional finite element modelling for dynamic water diffusion through stratum corneum. AB - Solvents penetration through in vivo human stratum corneum (SC) has always been an interesting research area for trans-dermal drug delivery studies, and the importance of intercellular routes (diffuse in between corneocytes) and transcellular routes (diffuse through corneocytes) during diffusion is often debatable. In this paper, we have developed a two dimensional finite element model to simulate the dynamic water diffusion through the SC. It is based on the brick-and-mortar model, with brick represents corneocytes and mortar represents lipids, respectively. It simulates the dynamic water diffusion process through the SC from pre-defined initial conditions and boundary conditions. Although the simulation is based on water diffusions, the principles can also be applied to the diffusions of other topical applied substances. The simulation results show that both intercellular routes and transcellular routes are important for water diffusion. Although intercellular routes have higher flux rates, most of the water still diffuse through transcellular routes because of the high cross area ratio of corneocytes and lipids. The diffusion water flux, or trans-epidermal water loss (TEWL), is reversely proportional to corneocyte size, i.e. the larger the corneocyte size, the lower the TEWL, and vice versa. There is also an effect of the SC thickness, external air conditions and diffusion coefficients on the water diffusion through SC on the resulting TEWL. PMID- 22310465 TI - Combination therapy with metronomic S-1 dosing and oxaliplatin-containing PEG coated cationic liposomes in a murine colorectal tumor model: synergy or antagonism? AB - Combination therapy with 2 or more drugs with different mechanisms of action has been considered a promising strategy for the effective treatment of advanced and metastatic cancers. However, the rational design of combination therapy represents a potential prerequisite for its effectiveness. Recently, we showed that the combination of oral metronomic S-1 dosing with oxaliplatin (l-OHP) containing PEG-coated "neutral" liposomes exerted excellent antitumor activity. In addition, we recently designed a PEG-coated "cationic" liposome for dual targeting delivery of l-OHP to tumor endothelial cells and tumor cells in a solid tumor. This targeted liposomal l-OHP formulation showed efficient antitumor activity in a murine tumor model, compared with l-OHP-containing PEG-coated "neutral" liposomes. In the present study, we investigated the issue of whether metronomic S-1 dosing with l-OHP-containing PEG-coated "cationic" liposomes creates synergy. Unfortunately, metronomic S-1 dosing resulted in impaired delivery of PEG-coated "cationic" liposomes into tumor tissue, presumably by decreasing the binding sites on tumor blood vessels available for the liposomes. The anticipated cytotoxic synergistic effect of the combination treatment was not achieved. Instead, the combination treatment showed lower antitumor efficacy than l-OHP-containing PEG-coated "cationic" liposomes alone. These results suggest that the combined treatment of S-1 and l-OHP-containing PEG-coated "cationic" liposomes seems to be antagonistic rather than synergistic. PMID- 22310466 TI - Aberrant stratifin overexpression is regulated by tumor-associated CpG demethylation in lung adenocarcinoma. AB - We previously have shown the aberrant overexpression of stratifin (SFN, 14-3-3 sigma) in lung adenocarcinoma. Although SFN is known to facilitate tumor cell proliferation, the mechanism that underlies its aberrant expression has remained unclear. SFN, the downstream target of p53, often has been reported to be hypermethylated and subsequently silenced in certain cancers; however, its hypomethylation-linked reactivation has not yet been validated. In this study, we investigated the DNA methylation status of the SFN promoter region using 8 lung cancer cell lines and 32 specimens of adenocarcinoma tissue. Real-time methylation-specific PCR analysis showed that although both normal lung tissue and adenocarcinoma in situ bore a completely methylated SFN promoter, the promoter region in almost all invasive adenocarcinomas was at least partially methylated. The expression of SFN and its level of methylation were correlated strongly. Furthermore, statistical analysis revealed that the level of methylation became reduced with progression of the pathologic stage, although no clear relationship between methylation level and p53 abnormality was found. These results suggest that methylation-related silencing of SFN occurs in both normal lung tissues and adenocarcinoma in situ, and that demethylation of the SFN promoter participates in the aberrant expression of SFN in invasive adenocarcinoma cells, independently of p53 alteration. This novel finding might be informative for clarifying the mechanism that underlies the progression of early lung adenocarcinoma. PMID- 22310468 TI - Ethics and equity: choice or compulsion? PMID- 22310467 TI - ProxTom lymphatic vessel reporter mice reveal Prox1 expression in the adrenal medulla, megakaryocytes, and platelets. AB - Lymphatic vessels (LVs) are important structures for antigen presentation, for lipid metabolism, and as conduits for tumor metastases, but they have been difficult to visualize in vivo. Prox1 is a transcription factor that is necessary for lymphangiogenesis in ontogeny and the maintenance of LVs. To visualize LVs in the lymph node of a living mouse in real time, we made the ProxTom transgenic mouse in a C57BL/6 background using red fluorescent LVs that are suitable for in vivo imaging. The ProxTom transgene contained all Prox1 regulatory sequences and was faithfully expressed in LVs coincident with endogenous Prox1 expression. The progenies of a ProxTom * Hec6stGFP cross were imaged using two-photon laser scanning microscopy, allowing the simultaneous visualization of LVs and high endothelial venules in a lymph node of a living mouse for the first time. We confirmed the expression of Prox1 in the adult liver, lens, and dentate gyrus. These intensely fluorescent mice revealed the expression of Prox1 in three novel sites: the neuroendocrine cells of the adrenal medulla, megakaryocytes, and platelets. The novel sites identified herein suggest previously unknown roles for Prox1. The faithful expression of the fluorescent reporter in ProxTom LVs indicates that these mice have potential utility in the study of diseases as diverse as lymphedema, filariasis, transplant rejection, obesity, and tumor metastasis. PMID- 22310469 TI - The A-allele of the common FTO gene variant rs9939609 complicates weight maintenance in severe obese patients. AB - OBJECTIVE: The A-allele of the fat mass and obesity-associated (FTO) gene variant rs9939609 has been associated with increased body weight, whereas no effect on weight loss during weight reduction programs has been observed. We questioned whether the AA-genotype interferes with weight stabilization after weight loss. DESIGN: We conducted a monocentric, longitudinal study involving obese individuals. The FTO gene variant rs9939609 was genotyped in participants attending a weight reduction program that was divided into two phases: a weight reduction period with formula diet (12 weeks) and a weight maintenance phase (40 weeks). Body weight, body mass index (BMI), blood pressure and concentrations of blood glucose, total cholesterol, low-density lipoprotein, high-density lipoprotein and triglycerides were determined in week 0 (T(0)), after 12 weeks (T(1)) and at the end in week 52 (T(2)). SUBJECTS: A total of 193 obese subjects aged between 18 and 72 years (129 female, 64 male; initial body weight: 122.4+/ 22.3 kg, initial BMI: 41.8+/-6.7 kg m(-2)) were included. RESULTS: Genotyping revealed 32.1% TT-, 39.4% AT- and 28.5% AA-genotype carriers. At T (0), carriers of the AA-genotype had significantly higher body weight (P=0.04) and BMI (P=0.005) than carriers of the TT-genotype. Of the 193 participants, 68 discontinued and 125 completed the program. Dropout rate was not influenced by genotype (P=0.33). Completers with AA-genotype showed significantly lower additional weight loss during the weight maintenance phase than TT-genotype carriers (P=0.02). Furthermore, among participants facing weight regain during weight maintenance (n=52), more subjects were carrying the AA-genotype (P=0.006). No influence of genotype on weight reduction under formula diet was observed (P=0.32). CONCLUSION: In this program, the AA-genotype of rs9939609 was associated with a higher initial body weight and did influence success of weight stabilization. Thus, emphasizing the maintenance phase during a weight reduction program might result in better success for AA-genotype carriers. PMID- 22310471 TI - Adiposity and sex hormones across the menstrual cycle: the BioCycle Study. AB - OBJECTIVE: To investigate the influence of adiposity on patterns of sex hormones across the menstrual cycle among regularly menstruating women. SUBJECTS: The BioCycle Study followed 239 healthy women for 1-2 menstrual cycles, with up to eight visits per cycle timed using fertility monitors. METHODS: Serum estradiol (E2), progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) were measured at each visit. Adiposity was measured by anthropometry and by dual energy X-ray absorptiometry (DXA). Differences in hormonal patterns by adiposity measures were estimated using nonlinear mixed models, which allow for comparisons in overall mean levels, amplitude (i.e., lowest to highest level within each cycle) and shifts in timing of peaks while adjusting for age, race, energy intake and physical activity. RESULTS: Compared with normal weight women (n=154), obese women (body mass index (BMI) ?30 kg m(-2), n=25) averaged lower levels of progesterone (-15%, P=0.003), LH (-17%, P=0.01), FSH (-23%, P=0.001) and higher free E2 (+22%, P=0.0001) across the cycle. To lesser magnitudes, overweight women (BMI: 25-30, n=60) also exhibited differences in the same directions for mean levels of free E2, FSH and LH. Obese women experienced greater changes in amplitude of LH (9%, P=0.002) and FSH (8%, P=0.004), but no differences were observed among overweight women. Higher central adiposity by top compared to bottom tertile of trunk-to-leg fat ratio by DXA was associated with lower total E2 (-14%, P=0.005), and FSH (-15%, P=0.001). Peaks in FSH and LH occurred later (~0.5 day) in the cycle among women with greater central adiposity. CONCLUSION: Greater total and central adiposity were associated with changes in mean hormone levels. The greater amplitudes observed among obese women suggest compensatory mechanisms at work to maintain hormonal homeostasis. Central adiposity may be more important in influencing timing of hormonal peaks than total adiposity. PMID- 22310470 TI - Additive feeding inhibitory and aversive effects of naltrexone and exendin-4 combinations. AB - OBJECTIVE: One developing strategy for obesity treatment has been to use combinations of differently acting pharmacotherapies to improve weight loss with fewer adverse effects. The purpose of this study was to determine whether the combination of naltrexone (Nal), an opioid antagonist acting on the reward system, and exendin-4 (Ex-4), a glucagon-like peptide 1 agonist acting on satiety signaling, would produce larger reductions in food intake than either alone in rats. Because the anorectic potencies of both compounds have been associated with nausea and malaise, the influence of these drug combinations on the acquisition of a conditioned taste aversion (CTA) was also determined. METHODS: In Experiment 1, the acute anorectic effects of Nal (0.32-3.2 mg kg(-1); intraperitoneally (i.p.)) and Ex-4 (1-10 MUg kg(-1); i.p.) were assessed alone or in combination. Combinational doses were further investigated by the repeated daily administration of 1 mg kg(-1) Nal+3.2 MUg kg(-1) Ex-4 for 4 days. In Experiment 2, both compounds alone or in combination were used as unconditioned stimuli in a series of CTA tests. RESULTS: Nal and Ex-4, alone or in combination, suppressed food intake in a dose-dependent manner, and the interaction on food intake between Nal and Ex-4 was additive. In the CTA paradigm, Nal (1 mg kg(-1)) alone did not support acquisition, whereas a CTA was evident with doses of Ex-4 (1 or 3.2 MUg kg(-1)). Combinations of Nal and Ex-4 also resulted in a more rapid and robust acquisition of a CTA. CONCLUSION: Given that the Nal and Ex-4 combination produces additive effects on not only food intake reduction but also food aversion learning, this specific drug combination does not have the benefit of minimizing the adverse effects associated with each individual drug. These data suggest that it is necessary to evaluate both the positive and adverse effects at early stages of combinational drug development. PMID- 22310472 TI - Effect of protein intake and weight gain velocity on body fat mass at 6 months of age: the EU Childhood Obesity Programme. AB - INTRODUCTION: Higher protein intake during the first year of life is associated with increased weight gain velocity and body mass index (BMI). However, the relationship of protein intake and weight gain velocity with body composition is unclear. OBJECTIVE: To assess if the increases in weight gain velocity and BMI induced by protein intake early in life are related to an increase in fat or fat free mass. MATERIALS AND METHODS: In all, 41 infants randomized at birth to a higher or lower protein content formula (HP=17 and LP=24, respectively) and 25 breastfed infants were included. Anthropometric measures were assessed at baseline, 6, 12 and 24 months, and fat-free mass (FFM) and fat mass (FM) were assessed by isotope dilution at 6 months. RESULTS: Weight gain velocity (g per month) during the first 6 months of life was significantly higher among HP infants (807.8 (+/-93.8) vs 724.2 (+/-110.0) (P=0.015)). Weight gain velocity strongly correlated with FM z-score (r=0.564, P<0.001) but showed no association with FFM z-scores. FFM showed no association with BMI. Nevertheless, FM strongly correlated with BMI at 6, 12 and 24 months (r=0.475, P<0.001; r=0.332, P=0.007 and r=0.247, P=0.051, respectively). FFM and FM z-scores did not differ significantly between HP and LP infants (0.32+/-1.75 vs -0.31+/-1.17 and 0.54+/ 2.81 vs -0.02+/-1.65, respectively). CONCLUSION: Our findings support the hypothesis that higher protein intakes early in life are associated with faster weight gain and in turn to higher adiposity. This mechanism could be a determinant factor for later obesity risk. PMID- 22310473 TI - SIRT1 and CLOCK 3111T> C combined genotype is associated with evening preference and weight loss resistance in a behavioral therapy treatment for obesity. AB - BACKGROUND: A new negative feedback loop has been proposed, which suggests connections between the circadian clock and SIRTUIN1 (SIRT1)-dependent functions associated with cell survival, development and metabolism. OBJECTIVE: To develop a SIRT1 and circadian locomotor output cycles kaput (CLOCK) combined genotype and to assess its associations with the chronotype of subjects and their potential resistance to weight loss in a behavioral treatment for obesity based on a Mediterranean diet. DESIGN: Overweight /obese subjects (n=1465), aged 20-65 years, who attended outpatient obesity clinics, were genotyped for SIRT1 (rs1467568) and CLOCK (3111T>C, rs1801260). Anthropometric, biochemical and dietary-intake variables were analyzed. Effectiveness of the program and weight loss progression during 30 weeks of treatment was assessed. RESULTS: We found highly consistent associations between the morning/evening questionnaires across the different genotype categories. Subjects carrying minor alleles at SIRT1 and CLOCK loci (R group) displayed a higher resistance to weight loss and a lower weekly weight loss rate as compared with homozygotes for both major alleles (P group). Significant differences were found across genotypes in weight loss progression during the 30 weeks of treatment (P=0.039). Dietary habits indicated that R carriers had a lower intake of total carbohydrates and monounsaturated fats, and a higher intake of saturated fats than those carrying the intermediate (M) and the P genotype (P=0.02). Plasma ghrelin concentrations were also significantly higher in subjects carrying the R genotype. CONCLUSION: Variants of both SIRT1 and CLOCK have an additive effect on resistance to weight loss that could be related to the chronotype of the subject, higher plasma levels of ghrelin and less adherence to Mediterranean diet patterns. PMID- 22310474 TI - Spatial accessibility to physical activity facilities and to food outlets and overweight in French youth. AB - OBJECTIVE: Some characteristics of the built environment have been associated with obesity in youth. Our aim was to determine whether individual and environmental socio-economic characteristics modulate the relation between youth overweight and spatial accessibility to physical activity (PA) facilities and to food outlets. DESIGN: Cross-sectional study. SUBJECTS: 3293 students, aged 12 +/- 0.6 years, randomly selected from eastern France middle schools. MEASUREMENTS AND METHODS: Using geographical information systems (GIS), spatial accessibility to PA facilities (urban and nature) was assessed using the distance to PA facilities at the municipality level; spatial accessibility to food outlets (general food outlets, bakeries and fast-food outlets) was calculated at individual level using the student home address and the food outlets addresses. Relations of weight status with spatial accessibility to PA facilities and to food outlets were analysed using mixed logistic models, testing potential direct and interaction effects of individual and environmental socio-economic characteristics. RESULTS: Individual socio-economic status modulated the relation between spatial accessibility to PA facilities and to general food outlets and overweight. The likelihood of being overweight was higher when spatial accessibility to urban PA facilities and to general food outlets was low, but in children of blue-collar workers only. The odds ratio (OR) (95% confidence interval) for being overweight of blue-collar-workers children compared with non-blue-collar-workers children was 1.76 (1.25-2.49) when spatial accessibility to urban PA facilities was low. This OR was 1.86 (1.20-2.86) when spatial accessibility to general food outlets was low. There was no significant relationship of overweight with either nature PA facilities or other food outlets (bakeries and fast-food outlets). CONCLUSION: These results indicate that disparities in spatial accessibility to PA facilities and to general food outlets may amplify the risk of overweight in socio economically disadvantaged youth. These data should be relevant for influencing health policies and urban planning at both a national and local level. PMID- 22310475 TI - A gene variant of 11beta-hydroxysteroid dehydrogenase type 1 is associated with obesity in children. AB - BACKGROUND: The 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) enzyme catalyses the regeneration of active cortisol from inert cortisone and plays a critical role in tissue-specific corticosteroid reactions; therefore, 11beta-HSD1 is a key molecule associated with the development of obesity. Despite evidence for its role in obesity, no genetic polymorphisms have been significantly associated with the disease per se. OBJECTIVE: The aim of this study was to evaluate whether HSD11B1 gene variants, which have never been studied before, are associated with obesity and its related traits, as well as its relation to biomarkers of inflammation, liver damage and cardiovascular disease in a cohort of Spanish children. DESIGN: We performed a prospective case-control study. SUBJECTS: A total of 534 children were examined and classified as being obese (n=292) or normal weight (n=242). Anthropometric and biochemical measurements related to obesity, including inflammation, liver damage and cardiovascular disease, were determined. Genomic DNA was extracted and 10 HSD11B1 gene single nucleotide polymorphisms (SNPs) were genotyped. RESULTS: A novel SNP, rs3753519, was strongly associated with obesity and this SNP was the only statistically significant HSD11B1 gene SNP remaining after a Bonferroni correction (odds ratio=1.97 for allelic effect, 95% confidence interval 1.23-3.16; P=0.004 and Bonferroni corrected P=0.046). In addition, this SNP was significantly and positively associated with increased body mass index (BMI), BMI z-score, weight, waist circumference, plasma gamma-glutamyl transpeptidase and plasma active plasminogen activator inhibitor 1. The SNP was negatively associated with plasma adiponectin and cortisol after adjusting for sex and age. None of the inflammation biomarkers tested were associated with the risk allele. CONCLUSION: These data, which link an HSD11B1 genotype with both disease prevalence and its related phenotypes, strongly support a role for the rs3753519 polymorphism in the pathogenesis of pediatric-onset obesity. PMID- 22310476 TI - Insulin receptor-independent upregulation of cellular glucose uptake. AB - BACKGROUND: Cellular glucose uptake can be enhanced by upregulating Ras signaling in either insulin-dependent or -independent manner. In presence of insulin and intact insulin signaling, Ras has a negligible role in glucose uptake. Conversely, when insulin signaling is impaired in obesity or diabetes, the insulin-independent Ras pathway may be valuable for enhancing glucose disposal. We previously reported that Ad36, a human adenovirus, enhances cellular glucose uptake by upregulating the Ras/Glut4 pathway. Here, we investigated if Ad36 upregulated Ras via the insulin-independent pathway, to enhance glucose uptake. Furthermore, uncontrolled upregulation of Ras is linked with oncogenic cell transformation, if the tumor-suppressor gene p53 is also downregulated. Hence, we determined if upregulation of Ras by Ad36 would induce oncogenic cell transformation. Finally, we determined the relevance of Ad36 to insulin resistance in humans. METHODS: Insulin receptor (IR) was knocked down with small interfering RNA in 3T3-L1 adipocytes, to determine if Ad36 increases the Ras/Glut4 pathway and glucose uptake without IR-signaling. Next, the effects of Ad36 on cell transformation and p53 abundance were determined. Finally, overweight or obese women were screened for seropositivity to Ad36, as an indicator of natural Ad36 infection. Associations of Ad36 infection with adiposity and C-reactive proteins (CRPs)-two key markers of insulin resistance, and with glucose disposal, were determined. RESULTS: Unaffected by IR knock-down, Ad36 significantly increased the Ras pathway, Glut4 translocation and glucose uptake in 3T3-L1 adipocytes. Despite Ras upregulation, Ad36 did not transform 3T3 L1 cells. This may be because Ad36 significantly increased p53 protein in 3T3-L1 cells or mice adipose tissue. Ad36 seropositivity was associated with greater adiposity and CRP levels, yet a significantly higher systemic glucose disposal rate. CONCLUSIONS: Overall, the study offers Ras/Glut4 pathway as an alternate to enhance glucose disposal when insulin signaling is impaired, and, importantly, provides Ad36 as a tool to understand the modulation of that pathway. PMID- 22310477 TI - Adenosine deaminases that act on RNA induce reproducible changes in abundance and sequence of embryonic miRNAs. AB - Adenosine deaminases that act on RNA bind double-stranded and structured RNAs and convert adenosines to inosines by hydrolytic deamination. Inosines are recognized as guanosines, and, hence, RNA editing alters the sequence information but also structure of RNAs. Editing by ADARs is widespread and essential for normal life and development. Precursors of miRNAs are abundantly edited by ADARs, but neither the abundance nor the consequences of miRNA editing has been firmly established. Using transgenic mouse embryos that are deficient in the two enzymatically active editing enzymes ADAR and ADARB1, we compare relative frequencies but also sequence composition of miRNAs in these genetically modified backgrounds to wild type mice by "next-generation sequencing." Deficiency of ADARB1 leads to a reproducible change in abundance of specific miRNAs and their predicted targets. Changes in miRNA abundance seem unrelated to editing events. Additional deletion of ADAR has surprisingly little impact on the mature miRNA repertoire, indicating that miRNA expression is primarily dependent on ADARB1. A-to-G transitions reflecting A-to-I editing events can be detected at few sites and at low frequency during the early embryonic stage investigated. Again, most editing events are ADARB1-dependent with only few editing sites being specifically edited by ADAR. Besides known editing events in miRNAs, a few novel, previously unknown editing events were identified. Some editing events are located to the seed region of miRNAs, opening the possibility that editing leads to their retargeting. PMID- 22310478 TI - Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. AB - Atopic dermatitis (AD) has long been associated with Staphylococcus aureus skin colonization or infection and is typically managed with regimens that include antimicrobial therapies. However, the role of microbial communities in the pathogenesis of AD is incompletely characterized. To assess the relationship between skin microbiota and disease progression, 16S ribosomal RNA bacterial gene sequencing was performed on DNA obtained directly from serial skin sampling of children with AD. The composition of bacterial communities was analyzed during AD disease states to identify characteristics associated with AD flares and improvement post-treatment. We found that microbial community structures at sites of disease predilection were dramatically different in AD patients compared with controls. Microbial diversity during AD flares was dependent on the presence or absence of recent AD treatments, with even intermittent treatment linked to greater bacterial diversity than no recent treatment. Treatment-associated changes in skin bacterial diversity suggest that AD treatments diversify skin bacteria preceding improvements in disease activity. In AD, the proportion of Staphylococcus sequences, particularly S. aureus, was greater during disease flares than at baseline or post-treatment, and correlated with worsened disease severity. Representation of the skin commensal S. epidermidis also significantly increased during flares. Increases in Streptococcus, Propionibacterium, and Corynebacterium species were observed following therapy. These findings reveal linkages between microbial communities and inflammatory diseases such as AD, and demonstrate that as compared with culture-based studies, higher resolution examination of microbiota associated with human disease provides novel insights into global shifts of bacteria relevant to disease progression and treatment. PMID- 22310479 TI - Toxicological biomarkers of 2,3,4,7,8-pentachlorodibenzofuran in proteins secreted by HepG2 cells. AB - Using a proteomic approach, a study was conducted for determination of the effects of 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PCDF) on proteins secreted by HepG2 cells. Briefly, HepG2 cells were exposed to various concentrations of 2,3,4,7,8-PCDF for 24 or 48h. MTT and comet assays were then conducted for determination of cytotoxicity and genotoxicity, respectively. Results of an MTT assay showed that 1nM of 2,3,4,7,8-PCDF was the maximum concentration that did not cause cell death. In addition, a dose- and time dependent increase of DNA damage was observed in HepG2 cells exposed to 2,3,4,7,8 PCDF. Therefore, two different concentrations of 2,3,4,7,8-PCDF, 1 and 5nM, were selected for further analysis of proteomic biomarkers using two different pI ranges (4-7 and 6-9) and large two dimensional gel electrophoresis. Results showed identification of 32 proteins ( 29 up- and 3 down-regulated) by nano-LC ESI-MS/MS and nano-ESI on a Q-TOF2 MS. Among these, the identities of pyridoxine 5'-phosphate oxidase, UDP-glucose 6-dehydrogenase, plasminogen activator inhibitor I precursor, plasminogen activator inhibitor-3, proteasome activator complex subunit 1, isoform 1 of 14-3-3 protein sigma, peptidyl-prolyl cis-trans isomerase A, 14-3-3 protein gamma, protein DJ-1, and nucleoside diphosphate kinase A were confirmed by western blot analysis. The differential expression of protein DJ-1, proteasome activator complex subunit 1 and plasminogen activator inhibitor-3 was further validated in plasma proteins from rats exposed to 2,3,4,7,8-PCDF. These proteins could be used as potential toxicological biomarkers of 2,3,4,7,8-PCDF. PMID- 22310480 TI - Charged single alpha-helices in proteomes revealed by a consensus prediction approach. AB - Charged single alpha-helices (CSAHs) constitute a recently recognized protein structural motif. Its presence and role is characterized in only a few proteins. To explore its general features, a comprehensive study is necessary. We have set up a consensus prediction method available as a web service (at http://csahserver.chem.elte.hu) and downloadable scripts capable of predicting CSAHs from protein sequences. Using our method, we have performed a comprehensive search on the UniProt database. We found that the motif is very rare but seems abundant in proteins involved in symbiosis and RNA binding/processing. Although there are related proteins with CSAH segments, the motif shows no deep conservation in protein families. We conclude that CSAH-containing proteins, although rare, are involved in many key biological processes. Their conservation pattern and prevalence in symbiosis-associated proteins suggest that they might be subjects of relatively rapid molecular evolution and thus can contribute to the emergence of novel functions. PMID- 22310482 TI - Classification of frontal cortex haemodynamic responses during cognitive tasks using wavelet transforms and machine learning algorithms. AB - Recent advances in neuroimaging demonstrate the potential of functional near infrared spectroscopy (fNIRS) for use in brain-computer interfaces (BCIs). fNIRS uses light in the near-infrared range to measure brain surface haemoglobin concentrations and thus determine human neural activity. Our primary goal in this study is to analyse brain haemodynamic responses for application in a BCI. Specifically, we develop an efficient signal processing algorithm to extract important mental-task-relevant neural features and obtain the best possible classification performance. We recorded brain haemodynamic responses due to frontal cortex brain activity from nine subjects using a 19-channel fNIRS system. Our algorithm is based on continuous wavelet transforms (CWTs) for multi-scale decomposition and a soft thresholding algorithm for de-noising. We adopted three machine learning algorithms and compared their performance. Good performance can be achieved by using the de-noised wavelet coefficients as input features for the classifier. Moreover, the classifier performance varied depending on the type of mother wavelet used for wavelet decomposition. Our quantitative results showed that CWTs can be used efficiently to extract important brain haemodynamic features at multiple frequencies if an appropriate mother wavelet function is chosen. The best classification results were obtained by a specific combination of input feature type and classifier. PMID- 22310483 TI - The importance of relational coordination and reciprocal learning for chronic illness care within primary care teams. AB - BACKGROUND: Recent research from a complexity theory perspective suggests that implementation of complex models of care, such as the Chronic Care Model (CCM), requires strong relationships and learning capacities among primary care teams. PURPOSES: Our primary aim was to assess the extent to which practice member perceptions of relational coordination and reciprocal learning were associated with the presence of CCM elements in community-based primary care practices. METHODOLOGY/APPROACH: We used baseline measures from a cluster randomized controlled trial testing a practice facilitation intervention to implement the CCM and improve risk factor control for patients with Type 2 diabetes in small primary care practices. Practice members (i.e., physicians, nonphysician providers, and staff) completed baseline assessments, which included the Relational Coordination Scale, Reciprocal Learning Scale, and the Assessment of Chronic Illness Care (ACIC) survey, along with items assessing individual and clinic characteristics. To assess the association between Relational Coordination, Reciprocal Learning, and ACIC, we used a series of hierarchical linear regression models accounting for clustering of individual practice members within clinics and controlling for individual- and practice-level characteristics and tested for mediation effects. FINDINGS: A total of 283 practice members from 39 clinics completed baseline measures. Relational Coordination scores were significantly and positively associated with ACIC scores (Model 1). When Reciprocal Learning was added, Relational Coordination remained a significant yet notably attenuated predictor of ACIC (Model 2). The mediation effect was significant (z = 9.3, p < .01); 24% of the association between Relational Coordination and ACIC scores was explained by Reciprocal Learning. Of the individual- and practice-level covariates included in Model 3, only the presence of an electronic medical record was significant; Relational Coordination and Reciprocal Learning remained significant independent predictors of ACIC. PRACTICE IMPLICATIONS: Efforts to implement complex models of care should incorporate strategies to strengthen relational coordination and reciprocal learning among team members. PMID- 22310484 TI - A comparison of patient care units with high versus low levels of missed nursing care. AB - BACKGROUND: In a previous study, the nursing staff on 110 patient care units in 10 hospitals participated in a quantitative study of missed nursing care. PURPOSE: The aim of this study was to gain an understanding of the differences in patient care units that had the most missed nursing care with those with the least missed nursing care. METHODOLOGY: Focus groups were conducted with the registered nurse staff on the 5 units with the most missed nursing care and 5 units with the least missed care. FINDINGS: Ten themes were identified: (a) staffing levels, (b) communication, (c) collective orientation, (d) backup, (e) monitoring, (f) leadership, (g) long tenure, (h) unit size, (i) trust, and (j) accountability. Taken together, the predominant difference found was that units with the least missed care had higher teamwork. PRACTICE IMPLICATIONS: Strategies for developing interventions to decrease missed care and increase teamwork are presented. PMID- 22310486 TI - Gas-to-solid shift of C 1s-excited benzene. AB - The gas-to-solid shift of benzene is reported in the C 1s-core level regime, where the C 1s -> pi*-transition is investigated between 284.0 eV and 286.5 eV. Simultaneous experiments on the gas phase and condensed species are used to determine the gas-to-solid shift within an accuracy of +/-5 meV. Specifically, it is observed that the vibrationally resolved C 1s -> pi*-transition in solid benzene is red-shifted by 55 +/- 5 meV relative to the transition of the isolated molecule. Contrary to previously reported experimental data and estimates this gas-to-solid shift is somewhat smaller than the gas-to-cluster shift. It is significantly smaller than that determined in previous work on gaseous and condensed benzene. These results are discussed in terms of structural properties of molecular clusters and solid benzene by involving ab initio calculations as well as processes leading to spectral shifts of core-excited variable size matter. Finally, changes in the shape of the C 1s -> pi*-band upon the formation of solid benzene and benzene clusters are discussed. PMID- 22310485 TI - The effect of perceived person-job fit on employee attitudes toward change in trauma centers. AB - BACKGROUND: Employee attitudes toward change are critical for health care organizations implementing new procedures and practices. When employees are more positive about the change, they are likely to behave in ways that support the change, whereas when employees are negative about the change, they will resist the changes. PURPOSE: This study examined how perceived person-job (demands abilities) fit influences attitudes toward change after an externally mandated change. Specifically, we propose that perceived person-job fit moderates the negative relationship between individual job impact and attitudes toward change. METHODOLOGY: We examined this issue in a sample of Level 1 trauma centers facing a regulatory mandate to develop an alcohol screening and brief intervention program. A survey of 200 providers within 20 trauma centers assessed perceived person-job fit, individual job impact, and attitudes toward change approximately 1 year after the mandate was enacted. RESULTS: Providers who perceived a better fit between their abilities and the new job demands were more positive about the change. Further, the impact of the alcohol screening and brief intervention program on attitudes toward change was mitigated by perceived fit, where the relationship between job impact and change attitudes was more negative for providers who perceived a worse fit as compared with those who perceived a better fit. PRACTICAL IMPLICATIONS: Successful implementation of changes to work processes and procedures requires provider support of the change. Management can enhance this support by improving perceived person-job fit through ongoing training sessions that enhance providers' abilities to implement the new procedures. PMID- 22310487 TI - Cultivation and identification of colon cancer stem cell-derived spheres from the Colo205 cell line. AB - Our group established a method to culture spheres under serum-free culture condition. However, the biological characteristics and the tumorigenicity of spheres are unknown. Here, we demonstrate that sphere cells expressed high levels of the putative colorectal cancer stem cell markers CD133 and CD44. The CD133 positive rates were 13.27 +/- 5.62, 52.71 +/- 16.97 and 16.47 +/- 2.45% in sphere cells, regular Colo205 cells and differentiated sphere cells, respectively, while the CD44-positive rates were 62.92 +/- 8.38, 79.06 +/- 12.10 and 47.80 +/- 2.5%, respectively, and the CD133/CD44-double-positive rates were 10.77 +/- 4.96, 46.89 +/- 19.17 and 12.41 +/- 2.27%, respectively (P < 0.05). Cancer sphere cells formed crypt-like structures in 3-D culture. Moreover, cells from cancer spheres exhibited more tumorigenicity than regular Colo205 cells in a xenograft assay. The cancer sphere cells displayed much higher oncogenicity than regular Colo205 cells to initiate neoplasms, as assayed by H&E staining, Musashi-1 staining and electron microscopy. Our findings indicated that the sphere cells were enriched with cancer stem cells (CSCs), and exhibited more proliferation capacity, more differentiation potential and especially more tumorigenicity than regular Colo205 cells in vitro and in vivo. Further isolation and characterization of these CSCs may provide new insights for novel therapeutic targets and prognostic markers. PMID- 22310488 TI - Angiotensin II type 1 receptor blockade partially attenuates hypoxia-induced pulmonary hypertension in newborn piglets: relationship with the nitrergic system. AB - The objective of this study was to observe possible interactions between the renin-angiotensin and nitrergic systems in chronic hypoxia-induced pulmonary hypertension in newborn piglets. Thirteen chronically instrumented newborn piglets (6.3 +/- 0.9 days; 2369 +/- 491 g) were randomly assigned to receive saline (placebo, P) or the AT(1) receptor (AT(1)-R) blocker L-158,809 (L) during 6 days of hypoxia (FiO(2) = 0.12). During hypoxia, pulmonary arterial pressure (Ppa; P < 0.0001), pulmonary vascular resistance (PVR; P < 0.02) and the pulmonary to systemic vascular resistance ratio (PVR/SVR; P < 0.05) were significantly attenuated in the L (N = 7) group compared to the P group (N = 6). Western blot analysis of lung proteins showed a significant decrease of endothelial NOS (eNOS) in both P and L animals, and of AT(1)-R in P animals during hypoxia compared to normoxic animals (C group, N = 5; P < 0.01 for all groups). AT(1)-R tended to decrease in L animals. Inducible NOS (iNOS) did not differ among P, L, and C animals and iNOS immunohistochemical staining in macrophages was significantly more intense in L than in P animals (P < 0.01). The vascular endothelium showed moderate or strong eNOS and AT(1)-R staining. Macrophages and pneumocytes showed moderate or strong iNOS and AT(1)-R staining, but C animals showed weak iNOS and AT(1)-R staining. Macrophages of L and P animals showed moderate and weak AT(2)-R staining, respectively, but the endothelium of all groups only showed weak staining. In conclusion, pulmonary hypertension induced by chronic hypoxia in newborn piglets is partially attenuated by AT(1)-R blockade. We suggest that AT(1)-R blockade might act through AT(2)-R and/or Mas receptors and the nitrergic system in the lungs of hypoxemic newborn piglets. PMID- 22310489 TI - A proton exchange membrane fabricated from a chemically heterogeneous nonwoven with sandwich structure by the program-controlled co-electrospinning process. AB - A composite proton exchange membrane containing electrospun nanofibers shows excellent oxidative stability and high proton conductivity as well as an extremely low activation energy of 1.30 kJ mol(-1). PMID- 22310490 TI - Manipulation of individual water molecules on CeO2(111). AB - Water molecules adsorbed on the CeO(2)(111) surface are investigated by non contact atomic force microscopy (NC-AFM) at several tip-sample temperatures ranging between 10 and 300 K. Depending on the strength of the tip-surface interaction, they appear as triangular protrusions extended over three surface oxygen atoms or as small pits at hollow sites. During NC-AFM imaging with the tip being close to the surface, occasionally the transfer of molecules between tip and surface or the tip-induced lateral displacement of water molecules to equivalent surface lattice sites is observed. We report how this situation can be exploited to produce controlled lateral manipulations. A protocol to manipulate the water molecules between pre-defined neighbouring equivalent adsorption sites of the regular lattice as well as across a surface oxygen vacancy is demonstrated. PMID- 22310491 TI - Intravitreal dexamethasone implant in patients with persistent diabetic macular edema. AB - PURPOSE: To evaluate the effects of a single injection of Ozurdex over 6 months in eyes with persistent diabetic macular edema (DME). METHODS: In this retrospective interventional study, 9 patients with decreased visual acuity, as a result of persistent DME, received Ozurdex (intravitreal dexamethasone implant 0.7 mg). Main outcome measures included changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). RESULTS: Nine eyes of 9 patients (5 males, 4 females; mean age 58 years) were included in the analysis. The mean duration of DME was 49.9 months (range 24-85). All patients had undergone previous treatments for DME (intravitreal injection of anti-vascular endothelial growth factor, steroids or laser photocoagulation) before entering the study. At baseline, the mean BCVA was 0.74 +/- 0.33 logMAR, and the mean CRT was 502 +/- 222.16 um. The mean BCVA was unchanged on the third day (0.74 +/- 0.38 logMAR, p = 0.5), improved to 0.62 +/- 0.32 logMAR (p = 0.02), 0.59 +/- 0.26 logMAR (p = 0.02) and 0.63 +/- 0.38 logMAR (p = 0.6) after the first, third and fourth months, respectively, and decreased again to 0.73 +/- 0.35 logMAR (p = 0.4) at 6 months. The mean CRT improved to 397 +/- 115.31 um (p = 0.17), 271 +/- 99.97 um (p = 0.007), 325 +/- 133.05 um (p = 0.03) and 462 +/- 176.48 um (p = 0.36) on the third day and after 1, 3 and 4 months of follow-up and then increased again to 537 +/- 265.42 um (p = 0.33) at 6 months. Eight patients needed retreatments in the sixth month. One eye developed a transient intraocular pressure (IOP) increase 1 month after injection, which was successfully managed with topical IOP lowering medication. CONCLUSION: In eyes with persistent DME, Ozurdex produces improvement in BCVA and CRT as soon as the first days after the injection. Such improvement is maintained until the fourth month. PMID- 22310492 TI - Re: detection of hepatic metastases: gadolinium-enhanced MR imaging versus superparamagnetic iron oxide-enhanced MR imaging versus diffusion-weighted imaging. PMID- 22310493 TI - Comparison of self- and clinician's ratings of Personal and Social Performance in patients with schizophrenia: the role of insight. AB - BACKGROUND: Patients with schizophrenia are often markedly impaired in their social functioning, partly independent of symptom severity. Few studies have examined patients' self-reporting of their social functioning, how a patient's self-perspective differs from third-party ratings, and whether or not the patients' self-rating of social functioning is influenced by their awareness of illness. SAMPLING AND METHODS: Based on the Personal and Social Performance (PSP) scale as a clinician-administered scale, a PSP self-rating scale for patients was developed. The study included 42 inpatients with schizophrenia. Instruments were the PSP scale, the PSP self-rating scale, the Clinical Global Impression-Severity Scale, and the Scale to Assess Unawareness of Mental Disorder. RESULTS: A significant correlation was found between PSP self- and clinician's rating for 'socially useful activities', whereas the other PSP subdimensions as well as the total score were not significantly correlated. For patients with high insight, a significantly positive association emerged with 'disturbing and aggressive behaviour', while there was no significant correlation between PSP self- and clinician's ratings for the patients with poor insight into their disorder. CONCLUSIONS: Patients and clinicians only marginally converge on their judgments concerning the patients' psychosocial functioning. Patients' insight may have a moderating role on the approximation of agreement between self- and third-party ratings. Results are discussed in line with the present literature regarding the accuracy of self-awareness in schizophrenia. PMID- 22310495 TI - A mechanism for simultaneous suppression of tone burst-evoked otoacoustic emissions. AB - Tone burst-evoked otoacoustic emission (TBOAE) components in response to a 1 kHz tone burst are suppressed by the simultaneous presence of tone bursts at higher frequencies. To date, the underlying cause of this "simultaneous suppression" of TBOAEs is unclear. This paper describes a potential mechanism based on local nonlinear interactions between basilar membrane (BM) travelling waves, and tests the extent to which it is able to account for this specific suppression phenomenon. A simple mathematical model based on local nonlinear interactions was developed, and its predictions for a range of tone burst pairs were compared to corresponding TBOAE suppression data recorded from fourteen normally hearing human ears at a level of 60 dB p.e. SPL. Model predictions and mean TBOAE suppression data showed close agreement for all pairs of tone bursts. These results suggest that simultaneous suppression of TBOAEs can be explained solely in terms of the local nonlinear interaction-based mechanism. However, the involvement of other mechanisms, involving components generated at places basal to their characteristic place along the BM, cannot be excluded. PMID- 22310494 TI - Screening for chemicals that affect hair cell death and survival in the zebrafish lateral line. AB - The zebrafish lateral line is an efficient model system for the evaluation of chemicals that protect and damage hair cells. Located on the surface of the body, lateral line hair cells are accessible for manipulation and visualization. The zebrafish lateral line system allows rapid screens of large chemical libraries, as well as subsequent thorough evaluation of interesting compounds. In this review, we focus on the results of our previous screens and the evolving methodology of our screens for chemicals that protect hair cells, and chemicals that damage hair cells using the zebrafish lateral line. PMID- 22310496 TI - Spectroscopic characterization of (57)Fe-enriched cytochrome c. AB - Investigation of the heme iron dynamics in cytochrome c with Mossbauer spectroscopy and especially nuclear resonance vibrational spectroscopy requires the replacement of the natural abundant heme iron with the (57)Fe isotope. For demetallization, we use a safer and milder ferrous sulfate-hydrochloric acid method in addition to the harsher commonly used hydrofluoric acid-based procedure. The structural integrity of the (57)Fe-reconstituted protein in both oxidation states is confirmed from absorption spectra and a detailed analysis of the rich resonance Raman spectra. These results reinforce the application of metal-substituted heme c proteins as reliable models for the native proteins. PMID- 22310497 TI - A tandem insertion vector for large-scale preparation of nucleosomal DNA. AB - We developed a novel nucleosome DNA template vector, pWMD01, which is optimized for the large-scale preparation of nucleosomal DNA. By using restricted digestion by SapI or EarI within its multicloning site, multiple half-nucleosome DNA units can be introduced unidirectionally into the vector at each subcloning step. Through this method, we constructed a plasmid that has 18 tandem repeats of a half-nucleosome 90-bp DNA unit containing c-Myb-binding sites in two subcloning cycles. This method enables the rapid, large-scale preparation of nucleosomal DNA with crystallization-grade quality. PMID- 22310498 TI - A simplified hydroethidine method for fast and accurate detection of superoxide production in isolated mitochondria. AB - Because superoxide is involved in various physiological processes, many efforts have been made to improve its accurate quantification. We optimized and validated a superoxide-specific and -sensitive detection method. The protocol is based on fluorescence detection of the superoxide-specific hydroethidine (HE) oxidation product, 2-hydroxyethidium. We established a method for the quantification of superoxide production in isolated mitochondria without the need for acetone extraction and purification chromatography as described in previous studies. PMID- 22310499 TI - Reducing agents affect inhibitory activities of compounds: results from multiple drug targets. AB - High-throughput screening (HTS) of large compound libraries has become a commonly used method for the identification of drug leads, and nonphysiological reducing agents have been widely used for HTS. However, a comparison of the difference in the HTS results based on the choice of reducing agent used and potency comparisons of selected inhibitors has not been done with the physiological reducing agent reduced glutathione (GSH). Here, we compared the effects of three reducing agents-dithiothreitol (DTT), beta-mercaptoethanol (beta-MCE), and tris(2 carboxyethyl)phosphine (TCEP)-as well as GSH against three drug target proteins. Approximately 100,000 compounds were computationally screened for each target protein, and experimental testing of high-scoring compounds (~560 compounds) with the four reducing agents surprisingly produced many nonoverlapping hits. More importantly, we found that various reducing agents altered inhibitor potency (IC(50)) from approximately 10 MUM with one reducing agent to complete loss (IC(50)>200 MUM) of inhibitory activity with another reducing agent. Therefore, the choice of reducing agent in an HTS is critical because this may lead to the pursuit of falsely identified active compounds or failure to identify the true active compounds. We demonstrate the feasibility of using GSH for in vitro HTS assays with these three target enzymes. PMID- 22310500 TI - Fluorescence-based assay probing regulator of G protein signaling partner proteins. AB - The regulator of G protein signaling (RGS) proteins are one of the essential modulators for the G protein system. Besides regulating G protein signaling by accelerating the GTPase activity of Galpha subunits, RGS proteins are implicated in exerting other functions; they are also known to be involved in several diseases. Moreover, the existence of a single RGS protein in plants and its seven transmembrane domain found in 2003 triggered efforts to unveil detailed structural and functional information of RGS proteins. We present a method for real-time examination of the protein-protein interactions between RGS and Galpha subunits. AtRGS1 from plants and RGS4 from mammals were site-directedly labeled with the fluorescent probe Lucifer yellow on engineered cysteine residues and used to interact with different Galpha subunits. The physical interactions can be revealed by monitoring the real-time fluorescence changes (8.6% fluorescence increase in mammals and 27.6% in plants); their correlations to functional exertion were shown with a GTPase accelerating activity assay and further confirmed by measurement of K(d). We validate the effectiveness of this method and suggest its application to the exploration of more RGS signaling partner proteins in physiological and pathological studies. PMID- 22310501 TI - Epidemiology and global policy in child health. AB - Global interest in child health has waxed and waned over the last 30 years. In the 1980s, the United Nations Children's Fund led the child survival revolution, focusing on growth monitoring, oral rehydration, breastfeeding promotion and immunizations. By the 1990s, however, global interest in the health of mothers and children had waned. Key indicators such as immunization rates, which had increased sharply in the 1980s, either stagnated or declined in the 1990s. Attempting to reverse this situation, concerned scientists and policy makers joined forces, building upon the Millennium Development Goals which included a specific target of a reduction in under-five mortality by two-thirds by 2015. Sound epidemiological research laid the foundation for selecting a handful of cost-effective interventions and advocating for their incorporation into national and international policies. Epidemiology then contributed to measuring coverage with these interventions, assessing which population groups are lagging behind, feeding this information back to policy makers on a continuous basis, and evaluating the impact of large-scale programmes. Focusing on childhood pneumonia, this paper shows how child health has improved considerably as a result of this renewed vigor and international collaboration. PMID- 22310502 TI - Art and images in psychiatry. Washington Crossing the Delaware. PMID- 22310503 TI - Negative symptoms and the failure to represent the expected reward value of actions: behavioral and computational modeling evidence. AB - CONTEXT: Negative symptoms are a core feature of schizophrenia, but their pathogenesis remains unclear. Negative symptoms are defined by the absence of normal function. However, there must be a productive mechanism that leads to this absence. OBJECTIVE: To test a reinforcement learning account suggesting that negative symptoms result from a failure in the representation of the expected value of rewards coupled with preserved loss-avoidance learning. DESIGN: Participants performed a probabilistic reinforcement learning paradigm involving stimulus pairs in which choices resulted in reward or in loss avoidance. Following training, participants indicated their valuation of the stimuli in a transfer test phase. Computational modeling was used to distinguish between alternative accounts of the data. SETTING: A tertiary care research outpatient clinic. PATIENTS: In total, 47 clinically stable patients with a diagnosis of schizophrenia or schizoaffective disorder and 28 healthy volunteers participated in the study. Patients were divided into a high-negative symptom group and a low negative symptom group. MAIN OUTCOME MEASURES: The number of choices leading to reward or loss avoidance, as well as performance in the transfer test phase. Quantitative fits from 3 different models were examined. RESULTS: Patients in the high-negative symptom group demonstrated impaired learning from rewards but intact loss-avoidance learning and failed to distinguish rewarding stimuli from loss-avoiding stimuli in the transfer test phase. Model fits revealed that patients in the high-negative symptom group were better characterized by an "actor-critic" model, learning stimulus-response associations, whereas control subjects and patients in the low-negative symptom group incorporated expected value of their actions ("Q learning") into the selection process. CONCLUSIONS: Negative symptoms in schizophrenia are associated with a specific reinforcement learning abnormality: patients with high-negative symptoms do not represent the expected value of rewards when making decisions but learn to avoid punishments through the use of prediction errors. This computational framework offers the potential to understand negative symptoms at a mechanistic level. PMID- 22310504 TI - First-time first-trimester induced abortion and risk of readmission to a psychiatric hospital in women with a history of treated mental disorder. AB - CONTEXT: Mental health problems are associated with women's reproductive decisions and predict poor mental health outcomes after abortion and childbirth. OBJECTIVES: To study whether having a first-trimester induced abortion influenced the risk of psychiatric readmission and compare findings with readmission risk in women with mental disorders giving birth. DESIGN: Survival analyses were performed in a population-based cohort study merging data from the Danish Civil Registration System, the Danish Psychiatric Central Register, and the Danish National Hospital Register from January 1,1994, to December 31, 2007. SETTING: Denmark. PARTICIPANTS: All women born in Denmark between 1962 and 1992 with a record of 1 or more psychiatric admissions at least 9 months before a first-time first-trimester induced abortion or childbirth. Main Outcome Measure Readmission at a psychiatric hospital with any type of mental disorder from 9 months before to 12 months after a first-time first-trimester induced abortion or childbirth. RESULTS: Relative risk (RR) for readmission risk 9 to 0 months before a first trimester induced abortion was 0.95 (95% CI, 0.73-1.23) compared with the first year after the abortion. This contrasts with a reduced risk of readmission before childbirth (RR, 0.56; 95% CI, 0.42-0.75) compared with the first year post partum. Proximity to previous psychiatric admission in particular predicted rehospitalization risks in both the abortion and the childbirth group. CONCLUSIONS: Risk of readmission is similar before and after first-time first trimester abortion, contrasting with a marked increased in risk of readmission post partum. We speculate that recent psychiatric episodes may influence women's decisions to have an induced abortion; however, this decision does not appear to influence the illness course in women with a history of treated mental disorders. PMID- 22310505 TI - Altered neural reward representations in pathological gamblers revealed by delay and probability discounting. AB - CONTEXT: The neural basis of excessive delay discounting and reduced risk sensitivity of pathological gamblers with a particular focus on subjective neural reward representations has not been previously examined. OBJECTIVE: To examine how pathological gamblers represent subjective reward value at a neural level and how this is affected by gambling severity. DESIGN: Model-based functional magnetic resonance imaging study with patients and control subjects. SETTING: Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf. PARTICIPANTS: Participants were recruited from the local community by advertisement and through self-help groups. A sample of 16 pathological gamblers (according to the DSM-IV definition) was matched by age, sex, smoking status, income, educational level, and handedness to 16 healthy controls. RESULTS: Pathological gamblers showed increased discounting of delayed rewards and a trend toward decreased discounting of probabilistic rewards compared with matched controls. At the neural level, a significant group * condition interaction indicated that reward representations in the gamblers were modulated in a condition-specific manner, such that they exhibited increased (delay discounting) and decreased (probability discounting) neural value correlations in the reward system. In addition, throughout the reward system, neuronal value signals for delayed rewards were negatively correlated with gambling severity. CONCLUSIONS: The results extend previous reports of a generally hypoactive reward system in pathological gamblers by showing that, even when subjective reward valuation is accounted for, gamblers still show altered reward representations. Furthermore, results point toward a gradual degradation of mesolimbic reward representations for delayed rewards during the course of pathological gambling. PMID- 22310507 TI - Semi-interpenetrating network of polyethylene glycol and photocrosslinkable chitosan as an in-situ-forming nerve adhesive. AB - An ideal adhesive for anastomosis of severed peripheral nerves should tolerate strains imposed on rejoined nerves. We use blends of photocrosslinkable 4 azidobenzoic acid-modified chitosan (Az-C) and polyethylene glycol (PEG) as a new in-situ-forming bioadhesive for anastomosing and stabilizing the injured nerves. Cryo-scanning electron microscopy suggests that the polymer blends form a semi interpenetrating network (semi-IPN), where PEG interpenetrates the Az-C network and reinforces it. Az-C/PEG semi-IPN gels have higher storage moduli than Az-C gel alone and fibrin glue. Nerves anastomosed with an Az-C/PEG gel tolerate a higher force than those with fibrin glue prior to failure. A series of ex vivo and in vitro cell experiments indicate the Az-C/PEG gels are compatible with nerve tissues and cells. In addition, Az-C/PEG gels release PEG over a prolonged period, providing sustained delivery of PEG, a potential aid for nerve cell preservation through membrane fusion. Az-C/PEG semi-IPN gels are promising bioadhesives for repairing severed peripheral nerves not only because of their improved mechanical properties but also because of their therapeutic potential and tissue compatibility. PMID- 22310506 TI - Brain anatomy and its relationship to behavior in adults with autism spectrum disorder: a multicenter magnetic resonance imaging study. AB - CONTEXT: There is consensus that autism spectrum disorder (ASD) is accompanied by differences in neuroanatomy. However, the neural substrates of ASD during adulthood, as well as how these relate to behavioral variation, remain poorly understood. OBJECTIVE: To identify brain regions and systems associated with ASD in a large, well-characterized sample of adults. DESIGN: Multicenter case-control design using quantitative magnetic resonance imaging. SETTING: Medical Research Council UK Autism Imaging Multicentre Study (MRC AIMS), with sites comprising the Institute of Psychiatry, Kings College London; the Autism Research Centre, University of Cambridge; and the Autism Research Group, University of Oxford. PARTICIPANTS: Eighty-nine men with ASD and 89 male control participants who did not differ significantly in mean age (26 and 28 years, respectively) and full scale IQ (110 and 113, respectively). MAIN OUTCOME MEASURES: (1) Between-group differences in regional neuroanatomy assessed by voxel-based morphometry and (2) distributed neural systems maximally correlated with ASD, as identified by partial least-squares analysis. RESULTS: Adults with ASD did not differ significantly from the controls in overall brain volume, confirming the results of smaller studies of individuals in this age group without intellectual disability. However, voxelwise comparison between groups revealed that individuals with ASD had significantly increased gray matter volume in the anterior temporal and dorsolateral prefrontal regions and significant reductions in the occipital and medial parietal regions compared with controls. These regional differences in neuroanatomy were significantly correlated with the severity of specific autistic symptoms. The large-scale neuroanatomic networks maximally correlated with ASD identified by partial least-squares analysis included the regions identified by voxel-based analysis, as well as the cerebellum, basal ganglia, amygdala, inferior parietal lobe, cingulate cortex, and various medial, orbital, and lateral prefrontal regions. We also observed spatially distributed reductions in white matter volume in participants with ASD. CONCLUSIONS: Adults with ASD have distributed differences in brain anatomy and connectivity that are associated with specific autistic features and traits. These results are compatible with the concept of autism as a syndrome characterized by atypical neural "connectivity." PMID- 22310508 TI - The validity and reliability of 5-Hz global positioning system units to measure team sport movement demands. AB - The purpose of this research was to investigate the validity and the reliability of 5-Hz MinimaxX global positioning system (GPS) units measuring athlete movement demands. A team sport simulation circuit (files collected from each unit = 12) and flying 50-m sprints (files collected from each unit = 34) were undertaken, during which the total distance covered; peak speed; player load; the distance covered; time spent and number of efforts performed walking, jogging, running, high-speed running, and sprinting were examined. Movement demands were also separately categorized into low-intensity activity, high-intensity running, and very high-intensity running. The results revealed that GPS was a valid and reliable measure of total distance covered (p > 0.05, percentage typical error of measurement [%TEM] < 5%) and peak speed (p > 0.05, %TEM 5-10%). Further, GPS was found to be a reliable measure of player load (%TEM 4.9%) and the distance covered, time spent, and number of efforts performed at certain velocity zones (%TEM <5% to >10%). The level of GPS error was found to increase along with the velocity of exercise. The findings demonstrated that GPS is capable of measuring movement demands performed at velocities <20 km.h(-1), whereas more caution is to be exercised when analyzing movement demands collected by using GPS velocities >20 km.h(-1). PMID- 22310509 TI - Global positioning system data analysis: velocity ranges and a new definition of sprinting for field sport athletes. AB - Global positioning system (GPS) technology has improved the speed, accuracy, and ease of time-motion analyses of field sport athletes. The large volume of numerical data generated by GPS technology is usually summarized by reporting the distance traveled and time spent in various locomotor categories (e.g., walking, jogging, and running). There are a variety of definitions used in the literature to represent these categories, which makes it nearly impossible to compare findings among studies. The purpose of this work was to propose standard definitions (velocity ranges) that were determined by an objective analysis of time-motion data. In addition, we discuss the limitations of the existing definition of a sprint and present a new definition of sprinting for field sport athletes. Twenty-five GPS data files collected from 5 different sports (men's and women's field hockey, men's and women's soccer, and Australian Rules Football) were analyzed to identify the average velocity distribution. A curve fitting process was then used to determine the optimal placement of 4 Gaussian curves representing the typical locomotor categories. Based on the findings of these analyses, we make recommendations about sport-specific velocity ranges to be used in future time-motion studies of field sport athletes. We also suggest that a sprint be defined as any movement that reaches or exceeds the sprint threshold velocity for at least 1 second and any movement with an acceleration that occurs within the highest 5% of accelerations found in the corresponding velocity range. From a practical perspective, these analyses provide conditioning coaches with information on the high-intensity sprinting demands of field sport athletes, while also providing a novel method of capturing maximal effort, short-duration sprints. PMID- 22310510 TI - Effects of low-intensity resistance exercise under acute systemic hypoxia on hormonal responses. AB - Previous studies have shown that low-intensity resistance exercises with vascular occlusion and slow movement effectively increase muscular size and strength. Researchers have speculated that local hypoxia by occlusion and slow movement may contribute to such adaptations via promoting anabolic hormone secretions by the local accumulation of metabolites. In this study, we determined the effects of low-intensity resistance exercise under acute systemic hypoxia on metabolic and hormonal responses. Eight male subjects participated in 2 experimental trials: (a) low-intensity resistance exercise while breathing normoxic air (normoxic resistance exercise [NR]), (b) low-intensity resistance exercise while breathing 13% oxygen (hypoxic resistance exercise [HR]). The resistance exercises (bench press and leg press) consisted of 14 repetitions for 5 sets at 50% of maximum strength with 1 minute of rest between sets. Blood lactate (LA), serum growth hormone (GH), norepinephrine (NE), testosterone, and cortisol concentrations were measured before normoxia and hypoxia exposures; 15 minutes after the exposures; and at 0, 15, and 30 minutes after the exercises. The LA levels significantly increased after exercises in both trials (p <= 0.05). The area under the curve for LA after exercises was significantly higher in the HR trial than in the NR trial (p <= 0.05). The GH significantly increased only after the HR trial (p <= 0.05). The NE and testosterone significantly increased after the exercises in both trials (p <= 0.05). Cortisol did not significantly change in both trials. These results suggest that low-intensity resistance exercise in the hypoxic condition caused greater metabolic and hormonal responses than that in the normoxic condition. Coaches may consider low-intensity resistance exercise under systemic hypoxia as a potential training method for athletes who need to maintain muscle mass and strength during the long in-season. PMID- 22310511 TI - Electromyographic normalization procedures for determining exercise intensity of closed chain exercises for strengthening the quadriceps femoris muscles. AB - The purpose of this study was to compare the electromyographic (EMG) amplitudes of the quadriceps femoris (QF) muscles during a maximum voluntary isometric contraction (MVIC) to submaximal and maximal dynamic concentric contractions during active exercises. A secondary purpose was to provide information about the type of contraction that may be most appropriate for normalization of EMG data if one wants to determine if a lower extremity closed chain exercise is of sufficient intensity to produce a strengthening response for the QF muscles. Sixty-eight young healthy volunteers (39 female, 29 male) with no lower extremity pain or injury participated in the study. Surface electrodes recorded EMG amplitudes from the vastus medialis obliquus (VMO), rectus femoris (RF), and vastus lateralis (VL) muscles during 5 different isometric and dynamic concentric exercises. The last 27 subjects performed an additional 4 exercises from which a second data set could be analyzed. Maximum isokinetic knee extension and moderate to maximum closed chain exercises activated the QF significantly more than a MVIC. A 40-cm. lateral step-up exercise produced EMG amplitudes of the QF muscles of similar magnitude as the maximum isokinetic knee extension exercises and would be an exercise that could be considered for strengthening the QF muscles. Most published EMG studies of exercises for the QF have been performed by comparing EMG amplitudes during dynamic exercises to a MVIC. This procedure can lead one to overestimate the value of a dynamic exercise for strengthening the QF muscles. We suggest that when studying the efficacy of a dynamic closed chain exercise for strengthening the QF muscles, the exercise be normalized to a dynamic maximum muscle contraction such as that obtained with knee extension during isokinetic testing. PMID- 22310512 TI - Are changes in maximal squat strength during preseason training reflected in changes in sprint performance in rugby league players? AB - Because previous research has shown a relationship between maximal squat strength and sprint performance, this study aimed to determine if changes in maximal squat strength were reflected in sprint performance. Nineteen professional rugby league players (height = 1.84 +/- 0.06 m, body mass [BM] = 96.2 +/- 11.11 kg, 1 repetition maximum [1RM] = 170.6 +/- 21.4 kg, 1RM/BM = 1.78 +/- 0.27) conducted 1RM squat and sprint tests (5, 10, and 20 m) before and immediately after 8 weeks of preseason strength (4-week Mesocycle) and power (4-week Mesocycle) training. Both absolute and relative squat strength values showed significant increases after the training period (pre: 170.6 +/- 21.4 kg, post: 200.8 +/- 19.0 kg, p < 0.001; 1RM/BM pre: 1.78 +/- 0.27 kg.kg(-1), post: 2.05 +/- 0.21 kg.kg(-1), p < 0.001; respectively), which was reflected in the significantly faster sprint performances over 5 m (pre: 1.05 +/- 0.06 seconds, post: 0.97 +/- 0.05 seconds, p < 0.001), 10 m (pre: 1.78 +/- 0.07 seconds, post: 1.65 +/- 0.08 seconds, p < 0.001), and 20 m (pre: 3.03 +/- 0.09 seconds, post: 2.85 +/- 0.11 seconds, p < 0.001) posttraining. Whether the improvements in sprint performance came as a direct consequence of increased strength or whether both are a function of the strength and power mesocycles incorporated into the players' preseason training is unclear. It is likely that the increased force production, noted via the increased squat performance, contributed to the improved sprint performances. To increase short sprint performance, athletes should, therefore, consider increasing maximal strength via the back squat. PMID- 22310513 TI - The effect of whole-body vibration on jump height and active range of movement in female dancers. AB - Whole-body vibration (WBV) has been shown to have beneficial effects on strength and power indices in sedentary and moderately trained individuals. The aim of this study was to investigate the effect of 4 weeks of WBV on jump height, active range of motion (AROM), and leg anthropometry in conservatoire dance students. Seventeen female dancers were randomly assigned to a control or intervention group. The intervention group trained for 30 seconds per position at a 35-Hz frequency, 8-mm displacement in the first 2 weeks, and 40 seconds at 40 Hz for the final 2 weeks, whereas the control group carried out the same exercises but without vibration stimulation. A significant (p < 0.01) difference in the intervention group was noted over time for vertical jump and active ROM. No significant changes over time were noted in the anthropometric data. In conclusion, WBV can be used as a beneficial supplemental training intervention to increase jump and active flexibility in highly trained dancers without corresponding increases in relative anthropometric data. PMID- 22310514 TI - Acute effects of countermovement jumping and sprinting on shot put performance. AB - The purpose of this study was to investigate the acute effects of countermovement jumping and sprinting on shot put performance in experienced shot putters. Ten shot putters (best performance 13.16-20.36 m) participated in the study. After a standard warm-up including jogging, stretching, and 4-6 submaximal puts, they performed 3 shot put attempts with maximum effort, separated with 1.5-minute interval. Three minutes later, they performed 3 maximal consecutive countermovement jumps (CMJs). Immediately after jumping, they performed 3 shot put attempts with maximum effort, separated with a 1.5-minute interval. One week later, they carried out a similar protocol, at similar external conditions, but they performed a bout of 20-m sprinting instead of the CMJs, to potentiate shot put performance. Muscular strength (1 repetition maximum in squat, snatch, bench press, incline bench press) and body composition (dual x-ray absorptiometry) were measured during the same training period (+/-10 days from the jumping and sprinting protocols). Shot put performance was significantly increased after the CMJs (15.45 +/- 2.36 vs. 15.85 +/- 2.41 m, p = 0.0003). Similarly, shot put performance was significantly increased after sprinting (15.34 +/- 2.41 vs. 15.90 +/- 2.46 m, p = 0.0007). The increase in performance after sprinting was significantly higher compared with the increase after jumping (2.64 +/- 1.59 vs. 3.74 +/- 1.88%, p = 0.02). In conclusion, the results of this study indicate that a standard warm-up protocol followed by 3 maximal bouts of shot put and either 3 consecutive countermovement jumps or a bout of 20-m sprinting induce an acute increase in shot put performance in experienced shot putters. PMID- 22310515 TI - Occurrence of fatigue during sets of static squat jumps performed at a variety of loads. AB - Research has identified that the optimal power load for static squat jumps (with no countermovement) is lower than the loads usually recommended for power training. Lower loads may permit the performance of additional repetitions before the onset of fatigue compared with heavier loads; therefore, the aim of this study was to determine the point of fatigue during squat jumps at various loads (0, 20, 40, 60% 1-repetition maximum [1RM]). Seventeen professional rugby league players performed sets of 6 squat jumps (with no countermovement), using 4 loading conditions (0, 20, 40, and 60% of 1RM back squat). Repeated measures analysis of variance revealed no significant differences (p > 0.05) in force, velocity, power, and displacement between repetitions, for the 0, 20, and 40% loading conditions. The 60% condition showed no significant difference (p > 0.05) in peak force between repetitions; however, velocity (1.12 + 0.10 and 1.18 + 0.11 m.s(-1)), power (3,385 + 343 and 3,617 + 396 W) and displacement (11.13 + 2.31 and 11.85 + 2.16 cm) were significantly (p < 0.02) lower during repetition 6 compared with repetition 2. These findings indicate that when performing squat jumps (with no countermovement) with a load <40% 1RM back squat, up to >6 repetitions can be completed without inducing fatigue and a minimum of 4-6 repetitions should be performed to achieve peak power output. When performing squat jumps (with no countermovement) with a load equal to the 60% 1RM only, 5 repetitions should be performed to minimize fatigue and ensure maintenance of velocity and power. PMID- 22310516 TI - Comparing the physical demands of friendly matches and small-sided games in semiprofessional soccer players. AB - This study compared the physical demands of friendly matches (FMs) and small sided games (SGs) in semiprofessional soccer players by means of global positioning system technology. Twenty-seven semiprofessional soccer players were monitored during 7 FMs and 9 sessions involving different SGs. Their physical profile was described on the basis of 20 variables related to distances and frequencies at different running speeds, the number of accelerations, and through global indicators of workload such as the work:rest ratio, player workload, and the exertion index. Results showed significant differences (p < 0.01) between SGs and FMs for the following variables: overall workload (SG > FM); the distribution of the distance covered in the speed zones 7.0-12.9 km.h(-1) (SG > FM) and >21 km.h(-1) (FM > SG); the distribution of time spent in certain speed zones (FM > SG: 0.0-6.9 and >21 km.h(-1); FM > SG: 7.0-12.9 km.h(-1)). More sprints per hour of play were performed during FMs, with greater mean durations and distances, greater maximum durations and distances, and a greater frequency per hour of play for sprints of 10-40 and >40 m (p < 0.01). The frequency of repeated high intensity efforts was higher during FM (p < 0.01). The results show that coaches and strength and conditioning professionals should consider FMs during their training routine to foster specific adaptations in the domain of high-intensity effort. PMID- 22310517 TI - Upper extremity sensorimotor control among collegiate football players. AB - Injuries stemming from shoulder instability are very common among athletes participating in contact sports, such as football. Previous research has shown that increased laxity negatively affects the function of the sensorimotor system potentially leading to a pathological cycle of shoulder dysfunction. Currently, there are no data detailing such effects among football players. Therefore, the purpose of this study was to examine the differences in upper extremity sensorimotor control among football players compared with that of a control group. Forty-five collegiate football players and 70 male control subjects with no previous experience in contact sports participated. All the subjects had no recent history of upper extremity injury. Each subject performed three 30-second upper extremity balance trials on each arm. The balance trials were conducted in a single-arm push-up position with the test arm in the center of a force platform and the subjects' feet on a labile device. The trials were averaged, and the differences in radial area deviation between groups were analyzed using separate 1-way analyses of variance (p < 0.05). The football players showed significantly more radial area deviation of the dominant (0.41 +/- 1.23 cm2, p = 0.02) and nondominant arms (0.47 +/- 1.63 cm2, p = 0.03) when compared with the control group. These results suggest that football players may have decreased sensorimotor control of the upper extremity compared with individuals with no contact sport experience. The decreased upper extremity sensorimotor control among the football players may be because of the frequent impacts accumulated during football participation. Football players may benefit from exercises that target the sensorimotor system. These findings may also be beneficial in the evaluation and treatment of various upper extremity injuries among football players. PMID- 22310518 TI - Regulating explosive resistance training intensity using the rating of perceived exertion. AB - Explosive resistance training (ERT) improves older adults' strength and power, and methods to make this form of training more accessible and useful to older adults are needed. The purpose of this study was to evaluate whether the rating of perceived exertion (RPE) scale would predict a broad range of ERT intensities on the leg press with older adults. If successful, then a load-RPE relationship could be used to regulate the intensity of training loads for ERT with older adults, allowing the elimination of maximal strength testing. Twenty-one older adults (>=65 years) with resistance training experience took part in 2 testing sessions. Session 1: Subjects performed high-velocity repetitions on the leg press for up to 9 loads (from 60 to 140% body weight) presented in quasi randomized order, and then reported their RPE for each load. Session 2: A 1 repetition maximum (1RM) strength test was conducted. Regression analysis revealed that the average RPE across subjects for each load strongly predicted the average %1RM across subjects (R2 = 99.5%; p < 0.001). This allows the establishment of a load-RPE relationship for use in selecting ERT loads for older adults on the leg press. For example, high-intensity loads (70-90% 1RM) that would elicit both strength and power gains when used with ERT aligned with an RPE of 14-16. Lighter loads that may be useful for training for power, but not strength (<70% 1RM), were identified with RPE scores of 13 and lower. The load RPE relationship may simplify the regulation of intensity of ERT with older adults on the leg press, where the exercising older adult could be guided to select loads according to their RPE. PMID- 22310519 TI - A new single work bout test to estimate critical power and anaerobic work capacity. AB - The purpose of this study was to develop a 3-minute, all-out test protocol using the Monark cycle ergometer for estimating the critical power (CP) and anaerobic work capacity (AWC) with the resistance based on body weight. Twelve moderately trained adults (mean age +/- SD = 23.2 +/- 3.5 years) performed an incremental cycle ergometer test to exhaustion. The CP and AWC were estimated from the original work limit (W(lim)) vs. time limit (T(lim)) relationship (CP(PT)) and a 3-minute all-out test (CP(3min)) against a fixed resistance and compared with the CP and AWC estimated from the new 3-minute tests on the Monark cycle ergometer (CP(3.5%) and CP(4.5%)). The resistance values for the CP(3.5%) and CP(4.5%) tests were set at 3.5 and 4.5% of the subject's body weight (kilograms). The results indicated that there were no significant differences (p > 0.05) among mean CP values for CP(PT) (178 +/- 47 W), CP(3.5%) (173 +/- 40 W), and CP(4.5%) (186 +/- 44 W). The mean CP(3min) (193 +/- 54 W), however, was significantly greater than CP(PT) and CP(3.5%). There were no significant differences in AWC for the CP(PT) (13,412 +/- 6,247 J), CP(3min) (10,895 +/- 2,923 J), and CP(4.5%) (9,842 +/- 4,394 J). The AWC values for the CP(PT) and CP(3min), however, were significantly greater than CP(3.5%) (8,357 +/- 2,946 J). The results of this study indicated that CP and AWC could be estimated from a single 3-minute work bout test on the Monark cycle ergometer with the resistance set at 4.5% of the body weight. A single work bout test with the resistance based on the individual's body weight provides a practical and accessible method to estimate CP and AWC. PMID- 22310520 TI - Salivary hormonal values from high-speed resistive exercise workouts. AB - Our study purpose examined salivary hormonal responses to high-speed resistive exercise. Healthy subjects (n = 45) performed 2 elbow flexor workouts on a novel (inertial kinetic exercise; Oconomowoc, WI, USA) strength training device. Our methods included saliva sample collection at both preexercise and immediately postexercise; workouts entailed two 60-second sets separated by a 90-second rest period. The samples were analyzed in duplicate for their testosterone and cortisol concentrations ([T], [C]). Average and maximum elbow flexor torque were measured from each exercise bout; they were later analyzed with a 2(gender) * 2(workout) analysis of variance (ANOVA) with repeated measures for workout. The [T] and [C] each underwent a 2(gender) * 2(time) ANOVA with repeated measures for time. A within-subject design was used to limit error variance. Average and maximum torque each had gender (men > women; p < 0.05) effects. The [T] elicited a 2-way interaction (p < 0.05), as men incurred a significant 14% increase over time, but women's values were unchanged. Yet multivariate regression revealed that 3 predictor variables (body mass and average and maximum torques) did not account for a significant amount of variance associated with the rise in male [T]. Changes in [C] were not significant. In conclusion, changes in [T] concur with the results from other studies that showed significant elevations in male [T], despite the brevity of current workouts and the rather modest volume of muscle mass engaged. Practical applications imply that salivary assays may be a viable alternative to blood draws from athletes, yet coaches and others who may administer this treatment should know that our results may have produced greater pre-post hormonal changes if postexercise sample collection had occurred at a later time point. PMID- 22310522 TI - Comparative effectiveness research in cardiovascular imaging survival of the fittest? PMID- 22310523 TI - Evaluation of the accuracy of a computer-aided diagnosis (CAD) system in breast ultrasound according to the radiologist's experience. AB - RATIONALE AND OBJECTIVES: The aim of this study was to evaluate the performance of a computer-aided diagnosis (CAD) system for breast ultrasound to improve the characterization of breast lesions detected on ultrasound by junior and senior radiologists. MATERIALS AND METHODS: One hundred sixty ultrasound breast lesions were randomly reviewed blindly by four radiologists with different levels of expertise (from 20 years [radiologist A] to 4 months [radiologist D]), with and without the help of an ultrasound CAD system (B-CAD version 2). All lesions had been biopsied. Sensitivity and specificity with and without CAD were calculated for each radiologist for the following evaluation criteria: Breast Imaging Reporting and Data System category and the final diagnosis (benign or malignant). Intrinsic sensitivity, specificity, and predictive values of CAD alone were also calculated. RESULTS: CAD detected all cancers, and its use increased radiologists' sensitivity scores when this was possible (with vs without CAD: radiologist A, 99% vs 99%; radiologist B, 96% vs 87%; radiologist C, 95% vs 88%; radiologist D, 91% vs 88%). Seven additional cancers were diagnosed. However, the low specificity of CAD (48%) decreased the specificity of radiologists, especially of the more experienced among them (with vs without CAD: radiologist A, 46% vs 70%; radiologist B, 58% vs 80%; radiologist C, 57% vs 69%; radiologist D, 71% vs 71%). CONCLUSIONS: CAD for breast ultrasound appears to be a useful tool for improving the diagnosis of malignant lesions for junior radiologists. Nevertheless, its low specificity must be taken into account to limit biopsies of benign lesions. PMID- 22310524 TI - CTA combined with CT perfusion for assessing the efficacy of anti-angiogenic therapy in rabbit VX2 tumors. AB - RATIONALE AND OBJECTIVES: The aim of this study was to validate the feasibility of assessing the efficacy of antiangiogenic therapy on VX2 tumors using three dimensional computed tomographic (CT) angiography (CTA) combined with CT perfusion. MATERIALS AND METHODS: Forty rabbits with VX2 tumors were randomly assigned to four groups according to different doses of antiangiogenic drug, which were administered intraperitoneally daily for 14 days. In each group, 10 animals were scanned using three-dimensional CTA and CT perfusion on days 1 and 2 after the latest administration of the drug. Tumor masses were sectioned, stained by immunohistochemistry, and processed for correlation between CT imaging and histology. RESULTS: The numbers of new tumor vessels from CTA were significantly different among the four groups (P < .001). As the dose of the drug increased, blood flow and blood volume on CT perfusion increased linearly, but the mean transit time and permeability surface-area product decreased linearly (P < .001). Immunohistochemical analyses showed that microvascular density decreased, while both luminal vascular number and mature vessel number increased linearly as the drug dose increased (P < .001). CT manifestations were correlated well with histologic findings (P < .05). CONCLUSIONS: It is feasible to assess the efficacy of antiangiogenic therapy on VX2 tumors using three-dimensional CTA combined with CT perfusion. Three-dimensional CTA can display the morphologic changes of tumor vessels, while CT perfusion can predict the functional changes of tumor vessels after antiangiogenic therapy. PMID- 22310525 TI - Student concerns and misconceptions about a career in radiology. PMID- 22310526 TI - Pedagoguery. PMID- 22310527 TI - The place of health and the health of place: dengue fever and urban governance in Putrajaya, Malaysia. AB - This case study investigates the connections among urban planning, governance and dengue fever in an emerging market context in the Global South. Key informant interviews were conducted with leading figures in public health, urban planning and governance in the planned city of Putrajaya, Malaysia. Drawing on theories of urban political ecology and ecosocial epidemiology, the qualitative study found the health of place - expressed as dengue-bearing mosquitoes and dengue fever in human bodies in the urban environment - was influenced by the place of health in a hierarchy of urban priorities. PMID- 22310528 TI - Hollow spherical mesoporous phosphosilicate nanoparticles as a delivery vehicle for an antibiotic drug. AB - Mesoporous phosphosilicate nanoparticles of hollow sphere architecture have been prepared hydrothermally for the first time under acidic pH conditions and this material is found to be efficient in encapsulating an antibiotic drug and its controlled release at physiological pH for possible cargo delivery applications. PMID- 22310529 TI - Profile of total IgG, IgG1, IgG2, IgG3 and IgG4 levels in sera of patients with paracoccidioidomycosis: treatment follow-up using Mexo and rPb27 as antigens in an ELISA. AB - The levels of total of IgG, IgG1, IgG2, IgG3 and IgG4 were evaluated in 54 patients with chronic paracoccidioidomycosis (PCM) before, during and after treatment using an enzyme-linked immunosorbent assay with Mexo and recombinant Pb27 (rPb27) as the antigens. Mexo was effective in distinguishing PCM patients from individuals in the negative control group (NC) based on total IgG and rPb27 performed worse than Mexo when these two groups were compared. IgG1, IgG2, IgG3 and IgG4 could not be used to clearly distinguish PCM patients from those in the NC group using either antigen. There was no clear relationship between antibody levels and the period of treatment. The majority of patients presented with decreased antibody levels during treatment, with no statistically significant differences among the different periods of treatment. Only IgG4 presented a negative correlation between its levels and clinical improvement during treatment. In total, 65% of untreated PCM patients showed reactivity against IgG4 when the Mexo antigen was used and this reactivity decreased over the course of treatment. There was a tendency towards decreasing antibody levels during treatment, but these antibody levels did not necessarily clear after the treatment was stopped. Mexo was useful for PCM diagnosis using total IgG; however, more studies are necessary before this antigen can be used in measuring the levels of total IgG and its subclasses for monitoring patients during treatment. PMID- 22310530 TI - The depuration dynamics of oysters (Crassostrea gigas) artificially contaminated with hepatitis A virus and human adenovirus. AB - Within the country of Brazil, Santa Catarina is a major shellfish producer. Detection of viral contamination is an important step to ensure production quality and consumer safety during this process. In this study, we used a depuration system and ultraviolet (UV) disinfection to eliminate viral pathogens from artificially infected oysters and analysed the results. Specifically, the oysters were contaminated with hepatitis A virus (HAV) or human adenovirus type 5 (HAdV5). After viral infection, the oysters were placed into a depuration tank and harvested after 48, 72 and 96 h. After sampling, various oyster tissues were dissected and homogenised and the viruses were eluted with alkaline conditions and precipitated with polyethylene glycol. The oyster samples were evaluated by cell culture methods, as well as polymerase chain reaction (PCR) and quantitative PCR. Moreover, at the end of the depuration period, the disinfected seawater was collected and analysed by PCR. The molecular assays showed that the HAdV5 genome was present in all of the depuration time samples, while the HAV genome was undetectable after 72 h of depuration. However, viral viability tests (integrated cell culture-PCR and immunofluorescence assay) indicated that both viruses were inactivated with 96 h of seawater recirculation. In conclusion, after 96 h of UV treatment, the depuration system studied in this work purified oysters that were artificially contaminated with HAdV5 and HAV. PMID- 22310531 TI - Prevalence of human papillomavirus and Epstein-Barr virus DNA in penile cancer cases from Brazil. AB - Penile cancer is a potentially mutilating disease. Although its occurrence is relatively rare worldwide, penile cancer rates can be high in developing countries. A few studies have been conducted on the involvement of human papillomavirus (HPV) in penile carcinoma, which have found HPV present in 30-70% of penile malignant lesions, with a higher prevalence of HPV 16 and 18. It has been assumed that cofactors, such as Epstein-Barr virus (EBV) infections, may play a role in the progression of penile neoplasia. The aim of this study was to determine HPV and EBV prevalence in 135 penile malignant lesions from Brazilian men through the use of MY09/11 polymerase chain reaction (PCR), type-specific PCR and restriction fragment length polymorphism analysis. HPV prevalence among the men tested was 60.7%. Of the men who tested positive, 27 presented with HPV 16 (29.7%), five with HPV 18 (5.5%), 21 with HPV 45 (23.1%) and nine with HPV 6 (9.9%). Seven mixed infections were detected (9.2%), while 11 cases remained untyped (13.4%). Regarding EBV positivity, 46.7% of the samples contained EBV DNA with EBV-1 as the most prevalent type (74.6%). More than 23% of the men were co infected with both HPV and EBV, while 35% presented exclusively with HPV DNA and 20% presented only with EBV DNA. Penile carcinoma aetiology has not been fully elucidated and the role of HPV and EBV infections individually or synergistically is still controversial. Hence, more studies are needed to determine their possible role in carcinogenesis. PMID- 22310532 TI - Genetic polymorphism in Taenia solium metacestodes from different Brazilian geographic areas. AB - The aim of the present study is to investigate genetic polymorphisms in Taenia solium metacestodes from different Brazilian geographical areas and to relate them to antibody recognition in serum samples of neurocysticercosis (NC) patients. Metacestodes were obtained from the Distrito Federal (DF), Bahia, Minas Gerais (MG) and Sao Paulo (SP) regions of Brazil. Samples of human sera from 49 individuals with NC, 68 individuals with other helminthiasis and 40 healthy volunteers were analysed (157 individuals in total). Antigens were prepared and used in enzyme-linked immunosorbent assay and western blotting assays to detect specific immunoglobulin G antibodies. Genetic distances between metacestode populations were analysed using random amplified polymorphic DNA (RAPD) analysis. Our results show that there was a higher frequency of reactivity in the DF region in the sera from NC patients (p < 0.05), while discrimination between active and inactive NC was seen only in extracts from the MG and SP regions (p < 0.05). Using RAPD, the sample from the DF region presented a greater increase compared to the other regions. A relationship between genetic polymorphisms among T. solium metacestodes from different areas in Brazil and the differences in antibody detection in patients with NC were established. PMID- 22310533 TI - Cellular characterisation of Candida tropicalis presenting fluconazole-related trailing growth. AB - We assessed fluconazole susceptibility in 52 Candida tropicalis clinical strains using seven antifungal susceptibility methods, including broth microdilution (BMD) [standard M27 A3 (with neutral and acid pH), ATB Fungus 3, Vitek 2 system and flow cytometric analysis] and agar-based methods (disk diffusion and E-test). Trailing growth, detection of cell-associated secreted aspartic proteases (Saps) and morphological and ultrastructural traits of these clinical strains were also examined. The ranges of fluconazole 24 h-minimum inhibitory concentration (MIC) values were similar among all methods. The essential agreement among the methods used for MIC determinations was excellent and all methods categorised all strains as susceptible, except for one strain that showed a minor error. The presence of the trailing effect was assessed by six methods. Trailing positivity was observed for 86.5-100% of the strains. The exception was the BMD-Ac method where trailing growth was not observed. Morphological and ultrastructural alterations were detected in C. tropicalis trailing cells, including mitochondrial swelling and cell walls with irregular shapes. We tested the production of Saps in 13 C. tropicalis strains expressing trailing growth through flow cytometry. Our results showed that all of the C. tropicalis strains up-regulated surface Sap expression after 24 h or 48 h of exposure to fluconazole, which was not observed in untreated yeast strains. We concluded that C. tropicalis strains expressing trailing growth presented some particular features on both biological and ultrastructural levels. PMID- 22310534 TI - Genetic diversity of Leishmania infantum field populations from Brazil. AB - Leishmania infantum (syn. Leishmania chagasi) is the etiological agent of visceral leishmaniasis (VL) in Brazil. The epidemiology of VL is poorly understood. Therefore, a more detailed molecular characterization at an intraspecific level is certainly needed. Herein, three independent molecular methods, multilocus microsatellite typing (MLMT), random amplification of polymorphic DNA (RAPD) and simple sequence repeats-polymerase chain reaction (SSR PCR), were used to evaluate the genetic diversity of 53 L. infantum isolates from five different endemic areas in Brazil. Population structures were inferred by distance-based and Bayesian-based approaches. Eighteen very similar genotypes were detected by MLMT, most of them differed in only one locus and no correlation was found between MLMT profiles, geographical origin or the estimated population structure. However, complex profiles composed of 182 bands obtained by both RAPD and SSR-PCR assays gave different results. Unweighted pair group method with arithmetic mean trees built from these data revealed a high degree of homogeneity within isolates of L. infantum. Interestingly, despite this genetic homogeneity, most of the isolates clustered according to their geographical origin. PMID- 22310535 TI - Profile of circulating levels of IL-1Ra, CXCL10/IP-10, CCL4/MIP-1beta and CCL2/MCP-1 in dengue fever and parvovirosis. AB - Dengue virus (DENV) and parvovirus B19 (B19V) infections are acute exanthematic febrile illnesses that are not easily differentiated on clinical grounds and affect the paediatric population. Patients with these acute exanthematic diseases were studied. Fever was more frequent in DENV than in B19V-infected patients. Arthritis/arthralgias with DENV infection were shown to be significantly more frequent in adults than in children. The circulating levels of interleukin (IL)-1 receptor antagonist (Ra), CXCL10/inducible protein-10 (IP-10), CCL4/macrophage inflammatory protein-1 beta and CCL2/monocyte chemotactic protein-1 (MCP-1) were determined by multiplex immunoassay in serum samples obtained from B19V (37) and DENV-infected (36) patients and from healthy individuals (7). Forward stepwise logistic regression analysis revealed that circulating CXCL10/IP-10 tends to be associated with DENV infection and that IL-1Ra was significantly associated with DENV infection. Similar analysis showed that circulating CCL2/MCP-1 tends to be associated with B19V infection. In dengue fever, increased circulating IL-1Ra may exert antipyretic actions in an effort to counteract the already increased concentrations of IL-1beta, while CXCL10/IP-10 was confirmed as a strong pro inflammatory marker. Recruitment of monocytes/macrophages and upregulation of the humoral immune response by CCL2/MCP-1 by B19V may be involved in the persistence of the infection. Children with B19V or DENV infections had levels of these cytokines similar to those of adult patients. PMID- 22310536 TI - Risk factors for vancomycin-resistant enterococci colonisation in critically ill patients. AB - Vancomycin-resistant enterococci (VRE) are important hospital pathogens and have become increasingly common in patients admitted to the intensive care unit (ICU). To determine the incidence and the risk factors associated with VRE colonisation among ICU patients, active surveillance cultures for VRE faecal carriages were carried out in patients admitted to the ICU of the University Hospital of Uberlandia, Minas Gerais, Brazil. Risk factors were assessed using a case-control study. Seventy-seven patients (23.1%) were found to be colonised with vanC VRE and only one patient (0.3%) was colonised with vanA VRE. Independent risk factors for VRE colonisation included nephropathy [odds ratio (OR) = 13.6, p < 0.001], prior antibiotic use (OR = 5.5, p < 0.03) and carbapenem use (OR = 17.3, p < 0.001). Our results showed a higher frequency (23.1%) of Enterococcus gallinarum and Enterococcus casseliflavus, species that are intrinsically resistant to low levels of vancomycin (vanC), without an associated infection, associated with prior antibiotic use, carbapenem use and nephropathy as comorbidity. This study is the first to demonstrate the risk factors associated with vanC VRE colonisation in ICU hospitalised patients. Although vanA and vanB enterococci are of great importance, the epidemiology of vanC VRE needs to be better understood. Even though the clinical relevance of vanC VRE is uncertain, these species are opportunistic pathogens and vanC VRE-colonised patients are a potential epidemiologic reservoir of resistance genes. PMID- 22310537 TI - Spoligotyping and variable number tandem repeat analysis of Mycobacterium bovis isolates from cattle in Brazil. AB - We performed spoligotyping and 12-mycobacterial interspersed repetitive unit variable number tandem repeats (MIRU-VNTRs) typing to characterise Mycobacterium bovis isolates collected from tissue samples of bovines with lesions suggestive for tuberculosis during slaughter inspection procedures in abattoirs in Brazil. High-quality genotypes were obtained with both procedures for 61 isolates that were obtained from 185 bovine tissue samples and all of these isolates were identified as M. bovis by conventional identification procedures. On the basis of the spoligotyping, 53 isolates were grouped into nine clusters and the remaining eight isolates were unique types, resulting in 17 spoligotypes. The majority of the Brazilian M. bovis isolates displayed spoligotype patterns that have been previously observed in strains isolated from cattle in other countries. MIRU-VNTR typing produced 16 distinct genotypes, with 53 isolates forming eight of the groups, and individual isolates with unique VNTR profiles forming the remaining eight groups. The allelic diversity of each VNTR locus was calculated and only two of the 12-MIRU-VNTR loci presented scores with either a moderate (0.4, MIRU16) or high (0.6, MIRU26) discriminatory index (h). Both typing methods produced similar discriminatory indexes (spoligotyping h = 0.85; MIRU-VNTR h = 0.86) and the combination of the two methods increased the h value to 0.94, resulting in 29 distinct patterns. These results confirm that spoligotyping and VNTR analysis are valuable tools for studying the molecular epidemiology of M. bovis infections in Brazil. PMID- 22310538 TI - Treatment of an Aedes aegypti colony with the Cry11Aa toxin for 54 generations results in the development of resistance. AB - To study the potential for the emergence of resistance in Aedes aegypti populations, a wild colony was subjected to selective pressure with Cry11Aa, one of four endotoxins that compose the Bacillus thuringiensis serovar israelensis toxin. This bacterium is the base component of the most important biopesticide used in the control of mosquitoes worldwide. After 54 generations of selection, significant resistance levels were observed. At the beginning of the selection experiment, the half lethal concentration was 26.3 ng/mL and had risen to 345.6 ng/mL by generation 54. The highest rate of resistance, 13.1, was detected in the 54th generation. Because digestive proteases play a key role in the processing and activation of B. thuringiensis toxin, we analysed the involvement of insect gut proteases in resistance to the Cry11Aa B. thuringiensis serovar israelensis toxin. The protease activity from larval gut extracts from the Cry11Aa resistant population was lower than that of the B. thuringiensisserovar israelensis susceptible colony. We suggest that differences in protoxin proteolysis could contribute to the resistance of this Ae. aegypti colony. PMID- 22310539 TI - A comparative study of the TF-Test(r), Kato-Katz, Hoffman-Pons-Janer, Willis and Baermann-Moraes coprologic methods for the detection of human parasitosis. AB - This study compares the diagnostic accuracy of the TF-Test((r)) (TFT) for human parasitosis with results obtained using the traditional Kato-Katz (KK), Hoffman Pons-Janer (HPJ), Willis and Baermann-Moraes (BM) techniques. Overall, four stool samples were taken from each individual; three alternate-day TFT stool samples and another sample that was collected in a universal container. Stool samples were taken from 331 inhabitants of the community of Quilombola Santa Cruz. The gold standard (GS) for protozoa detection was defined as the combined results for TFT, HPJ and Willis coproscopic techniques; for helminth detection, GS was defined as the combined results for all five coproscopic techniques (TFT, KK, HPJ, Willis and BM). The positivity rate of each method was compared using the McNemar test. While the TFT exhibited similar positivity rates to the GS for Entamoeba histolytica/dispar (82.4%) and Giardia duodenalis (90%), HPJ and Willis techniques exhibited significantly lower positivity rates for these protozoa. All tests exhibited significantly lower positivity rates compared with GS for the diagnosis of helminths. The KK technique had the highest positivity rate for diagnosing Schistosoma mansoni (74.6%), while the TFT had the highest positivity rates for Ascaris lumbricoides (58.1%) and hookworm (75%); HPJ technique had the highest positivity rate for Strongyloides stercoralis (50%). Although a combination of tests is the most accurate method for the diagnosis of enteral parasites, the TFT reliably estimates the prevalence of protozoa and selected helminths, such as A. lumbricoides and hookworm. Further studies are needed to evaluate the detection accuracy of the TFT in samples with varying numbers of parasites. PMID- 22310540 TI - Comparison of two PCR methods for detection of Leptospira interrogans in formalin fixed and paraffin-embedded tissues. AB - In this study we compared two polymerase chain reaction (PCR) methods using either 16S ribosomal RNA (rRNA) or 23S rRNA gene primers for the detection of different Leptospira interrogans serovars. The performance of these two methods was assessed using DNA extracted from bovine tissues previously inoculated with several bacterial suspensions. PCR was performed on the same tissues before and after the formalin-fixed, paraffin-embedding procedure (FFPE tissues). The 23S rDNA PCR detected all fresh and FFPE positive tissues while the 16S rDNA-based protocol detected primarily the positive fresh tissues. Both methods are specific for pathogenic L. interrogans. The 23S-based PCR method successfully detected Leptospira in four dubious cases of human leptospirosis from archival tissue specimens and one leptospirosis-positive canine specimen. A sensitive method for leptospirosis identification in FFPE tissues would be a useful tool to screen histological specimen archives and gain a better assessment of human leptospirosis prevalence, especially in tropical countries, where large outbreaks can occur following the rainy season. PMID- 22310541 TI - Establishment and characterisation of a new cell line derived from Culex quinquefasciatus (Diptera: Culicidae). AB - Insect cell cultures are an important biotechnological tool for basic and applied studies. The objective of this work was to establish and characterise a new cell line from Culex quinquefasciatus embryonic tissues. Embryonated eggs were taken as a source of tissue to make explants that were seeded in L-15, Grace's, Grace's/L-15, MM/VP12, Schneider's and DMEM culture media with a pH range from 6.7-6.9 and incubated at 28oC. The morphological, cytogenetic, biochemical and molecular characteristics of the cell cultures were examined by observing the cell shapes, obtaining the karyotypes, using a cellulose-acetate electrophoretic system and performing random amplified polymorphic DNA-polymerase chain reaction analysis, respectively. The Grace's/L-15 medium provided the optimal nutritional conditions for cell adhesion and proliferation. Approximately 40-60 days following the explant procedure, a confluent monolayer was formed. Cellular morphology in the primary cultures and the subcultures was heterogeneous, but in the monolayer the epithelioid morphology type predominated. A karyotype with a diploid number of six chromosomes (2n = 6) was observed. Isoenzymatic and molecular patterns of the mosquito cell cultures matched those obtained from the immature and adult forms of the same species. Eighteen subcultures were generated. These cell cultures potentially constitute a useful tool for use in biomedical applications. PMID- 22310542 TI - HIV-1 tropism and CD4 T lymphocyte recovery in a prospective cohort of patients initiating HAART in Ribeirao Preto, Brazil. AB - While human immunodeficiency virus (HIV)-1 chemokine co-receptors 5 tropism and the GWGR motif in the envelope third variable region (V3 loop) have been associated with a slower disease progression, their influence on antiretroviral response remains unclear. The impact of baseline V3 characteristics on treatment response was evaluated in a randomised, double blind, prospective cohort study with patients initiating highly active antiretroviral therapy with lopinavir or efavirenz plus azithothymidine/3TC (1:1) over 48 weeks. Similar virological and immunological responses were observed for both treatment regimens. The 43 individuals had a mean baseline CD4 T cell count of 119 cells/mm(3) [standard deviation (SD) = 99] and a mean viral load of 5.09 log(10) copies/mL (SD = 0.49). The GWGR motif was not associated with a CD4 T cell response, but predicted R5 tropism by the geno2pheno([clinical20%]) algorithm correlated with higher CD4 T cell levels at all monitoring points (p < 0.05). Moreover, higher false-positive rates (FPR) values from this analysis revealed a strong correlation with CD4 T cell recovery (p < 0.0001). Transmitted drug resistance mutations, documented in 3/41 (7.3%) cases, were unrelated to the assigned antiretroviral regimen and had no impact on patient outcomes. In conclusion, naIve HIV-1 R5 infected patients exhibited higher CD4 T cell counts at baseline; this difference was sustained throughout therapy. The geno2pheno([clinical]) option FPR positively correlated with CD4 T cell gain and may be useful in predicting CD4 T cell recovery. PMID- 22310543 TI - Simulium (Psilopelmia) virescens, a new black-fly species (Diptera: Simuliidae) from the southwestern region of the state of Bahia, Brazil. AB - The last-instar larva, pupa, male and female of Simulium virescens sp. nov. are described and illustrated. This species has a peculiar larva, which has an elongated head capsule and light-green colour. The first thoracic segment has tubercle on its dorsal region and the third thoracic segment has one pair of tubercles; the first to the fourth abdominal segments have one pair of tubercles on each segment. Until now this new species had only been collected at the type locality, which is on the middle stretch of the Correntina River in the southwestern portion of the state of Bahia, Brazil. Females were voraciously biting humans during the field work. This new species represents the second species of Simulium (Psilopelmia) in Brazil and the first registered outside of the Brazilian Amazon Region. PMID- 22310544 TI - DNA multigene sequencing of topotypic specimens of the fascioliasis vector Lymnaea diaphana and phylogenetic analysis of the genus Pectinidens (Gastropoda). AB - Freshwater lymnaeid snails are crucial in defining transmission and epidemiology of fascioliasis. In South America, human endemic areas are related to high altitudes in Andean regions. The species Lymnaea diaphana has, however, been involved in low altitude areas of Chile, Argentina and Peru where human infection also occurs. Complete nuclear ribosomal DNA 18S, internal transcribed spacer (ITS)-2 and ITS-1 and fragments of mitochondrial DNA 16S and cytochrome c oxidase (cox)1 genes of L. diaphana specimens from its type locality offered 1,848, 495, 520, 424 and 672 bp long sequences. Comparisons with New and Old World Galba/Fossaria, Palaearctic stagnicolines, Nearctic stagnicolines, Old World Radix and Pseudosuccinea allowed to conclude that (i) L. diaphana shows sequences very different from all other lymnaeids, (ii) each marker allows its differentiation, except cox1 amino acid sequence, and (iii) L. diaphana is not a fossarine lymnaeid, but rather an archaic relict form derived from the oldest North American stagnicoline ancestors. Phylogeny and large genetic distances support the genus Pectinidens as the first stagnicoline representative in the southern hemisphere, including colonization of extreme world regions, as most southern Patagonia, long time ago. The phylogenetic link of L. diaphana with the stagnicoline group may give light to the aforementioned peculiar low altitude epidemiological scenario of fascioliasis. PMID- 22310545 TI - First detection of Rio Negro virus (Venezuelan equine encephalitis complex subtype VI) in Cordoba, Argentina. AB - Rio Negro virus (RNV) (Venezuelan equine encephalitis subtype VI) circulates only in Argentina; in northern provinces, isolates have been obtained from mosquitoes and rodents since 1980 and have been associated with acute febrile illness in humans. However, no studies of RNV have been performed in the central area of the country. We carried out molecular and serological detection of RNV in Cordoba, a province of the central part of the country, in mosquitoes and humans, respectively. One mosquito pool tested positive for alphavirus RNA by reverse transcriptase-nested polymerase chain reaction (RT-nested PCR). Subsequent sequencing determined that this alphavirus grouped with RNV. Serological studies detected antibodies to RNV in one human serum sample, which was obtained during the same period that RNV was detected using the aforementioned molecular methods. This is the first report of RNV circulation in the central area of Argentina, indicating an expansion of its original distribution. These results highlight the importance of strengthening surveillance procedures in endemic areas, as well as in new regions where RNV may emerge. PMID- 22310546 TI - Pfcrt haplotypes and the evolutionary history of chloroquine-resistant Plasmodium falciparum. AB - Mutations in the Pfcrt gene that change the resulting amino acids and form different haplotypes are common and correlate with the prevalence of chloroquine resistant (CQR) field isolates of the malaria parasite, Plasmodium falciparum. This correlation provides opportunities to infer the global evolutionary history of CQ resistance by analysing CQR Pfcrt haplotype data. We collated data on the Pfcrt haplotypes from different global studies and performed evolutionary genetic analysis to present comprehensive and comparative information on the global distribution of five major CQR-Pfcrt haplotypes and evolutionary inter relationships among 38 different countries. Using the haplotype diversity data, inter-continental genetic differentiation was also ascertained. PMID- 22310547 TI - Serological evidence of hantavirus infection in rural and urban regions in the state of Amazonas, Brazil. AB - Hantavirus disease is caused by the hantavirus, which is an RNA virus belonging to the family Bunyaviridae. Hantavirus disease is an anthropozoonotic infection transmitted through the inhalation of aerosols from the excreta of hantavirus infected rodents. In the county of Itacoatiara in the state of Amazonas (AM), Brazil, the first human cases of hantavirus pulmonary and cardiovascular syndrome were described in July 2004. These first cases were followed by two fatal cases, one in the municipality of Maues in 2005 and another in Itacoatiara in 2007. In this study, we investigated the antibody levels to hantavirus in a population of 1,731 individuals from four different counties of AM. Sera were tested by IgG/IgM enzyme-linked immune-sorbent assay using a recombinant nucleocapsid protein of the Araraquara hantavirus as an antigen. Ten sera were IgG positive to hantavirus (0.6%). Among the positive sera, 0.8% (1/122), 0.4% (1/256), 0.2% (1/556) and 0.9% (7/797) were from Atalaia do Norte, Careiro Castanho, Itacoatiara and Labrea, respectively. None of the sera in this survey were IgM-positive. Because these counties are distributed in different areas of AM, we can assume that infected individuals are found throughout the entire state, which suggests that hantavirus disease could be a local emerging health problem. PMID- 22310548 TI - Recognition of enteroinvasive Escherichia coli and Shigella flexneri by dendritic cells: distinct dendritic cell activation states. AB - The innate and adaptive immune responses of dendritic cells (DCs) to enteroinvasive Escherichia coli (EIEC) infection were compared with DC responses to Shigella flexneri infection. EIEC triggered DCs to produce interleukin (IL) 10, IL-12 and tumour necrosis factor (TNF)-alpha, whereas S. flexneri induced only the production of TNF-alpha. Unlike S. flexneri, EIEC strongly increased the expression of toll like receptor (TLR)-4 and TLR-5 in DCs and diminished the expression of co-stimulatory molecules that may cooperate to inhibit CD4(+) T lymphocyte proliferation. The inflammation elicited by EIEC seems to be related to innate immunity both because of the aforementioned results and because only EIEC were able to stimulate DC transmigration across polarised Caco-2 cell monolayers, a mechanism likely to be associated with the secretion of CC chemokine ligands (CCL)20 and TNF-alpha. Understanding intestinal DC biology is critical to unravelling the infection strategies of EIEC and may aid in the design of treatments for infectious diseases. PMID- 22310549 TI - Comparative evaluation under routine conditions of the nitrate reduction assay, the proportion assay and the MGIT 960 assay for drug susceptibility testing of clinical isolates of Mycobacterium tuberculosis. AB - The performance of the nitrate reductase assay (NRA) was compared with the proportion method (PM) on Lowenstein-Jensen medium and the BACTEC MGIT960 assay under routine conditions using 160 clinical isolates of Mycobacterium tuberculosis with a high proportion of resistant strains. The mean time to obtain results was 8.8 days and the overall agreements between NRA and PM and NRA and M960 were 95% and 94%, respectively. NRA was easy to perform and represents a useful tool for the rapid screening of drug-resistant M. tuberculosis strains in low-resource countries. PMID- 22310551 TI - Familial aggregation of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia with solid tumors and myeloid malignancies. AB - Lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM) is a B-cell disorder resulting from the accumulation, predominantly in the bone marrow, of clonally related lymphoplasmacytic cells. LPL/WM is a very rare disease, with an incidence rate of 3-4 cases per million people per year.Currently, the causes of LPL/WM are poorly understood; however, there are emerging data to support a role for immune-related factors in the pathogenesis of LPL/WM. In addition, data show that genetic factors are of importance in the etiology of LPL/WM. In this paper, we will review the current knowledge about familiality of LPL/WM and provide novel data on solid tumors and myeloid malignancies in first-degree relatives of LPL/WM patients. PMID- 22310552 TI - Holistic quality evaluation of commercial white and red ginseng using a UPLC-QTOF MS/MS-based metabolomics approach. AB - In traditional Chinese medicine practice, white ginseng (WG) and red ginseng (RG) have traditionally been used for different purposes. In the present study, an ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS)-based metabolomics approach was developed to evaluate the holistic qualities and to explore characteristic chemical components of commercial WG and RG. Through unsupervised principal component analysis (PCA) and supervised orthogonal partial least squared discrimination analysis (OPLS-DA) of the data from UPLC-QTOF-MS/MS, holistic quality inconsistencies of commercial WG and RG were identified, and the possible reasons involved were deduced by further elucidating the characteristic components of the groups. Heat treating and sulfur-fumigation were likely the main reasons for the quality differences in WG, and non-standardized processing procedures might have caused the inconsistent quality of RG. Together with ginsenoside Rg(3), a nitrogen-containing component and ginsenoside 20(R)-Rh(1) were detected as characteristic components of RG, whereas malonyl ginsenoside Rb(1)/isomer and malonyl ginsenoside Rg(1)/isomer were found to be characteristic components of WG. It was suggested that post harvest handling procedures for WG and processing procedures for RG should be standardized using the identified characteristic components as chemical markers to ensure the consistent quality and consequently the efficacy of WG and RG. PMID- 22310553 TI - Application of design of experiments and design space methodology for the HPLC-UV separation optimization of aporphine alkaloids from leaves of Spirospermum penduliflorum Thouars. AB - Spirospermum penduliflorum Thouars (Menispermaceae) is an endemic species of Madagascar traditionally used as vasorelaxant. Recently, two aporphine alkaloids known to possess antihypertensive activity (dicentrine and neolitsine) were isolated and identified from the leaves of this plant. In the present study, a HPLC-UV method allowing the separation of all alkaloids and the quantification of dicentrine in the alkaloidic extract of leaves was developed using design of experiments and design space methodology. Three common chromatographic parameters (i.e. the mobile phase pH, the initial proportion of methanol and the gradient slope) were selected to construct a full factorial design of 36 experimental conditions. The times at the beginning, the apex (i.e. the retention time) and the end of each peak were recorded and modelled by multiple linear equations. The corresponding residuals were normally distributed which confirmed that the models can be used for the prediction of the retention times and to optimize the separation. The optimal separation was predicted at pH 3, with a gradient starting at 32% of methanol and a gradient slope of 0.42%/min. Good agreement was obtained between predicted and experimental chromatograms. The method was also validated using total error concept. Using the accuracy profile approach, validation results gave a LOD and LOQ for dicentrine of 3 MUg/ml and 10 MUg/ml, respectively. A relative standard deviation for intermediate precision lower than 10% was obtained. This method was found to provide accurate results in the concentration range of 10-75 MUg/ml of dicentrine and is suitable for routine analysis. PMID- 22310554 TI - In vitro study on metabolite profiles of bioactive xanthones isolated from Halenia elliptica D. Don by high performance liquid chromatography coupled to ion trap time-of-flight mass spectrometry. AB - The metabolisms of five xanthones isolated from a Tibetan medicinal herb Halenia elliptica D. Don, including 1-hydroxy-2,3,5-trimethoxy-xanthone (HM-1), 1-hydroxy 2,3,4,7-tetramethoxy-xanthone (HM-2), 1-hydroxy-2,3,4,5-tetramethoxy-xanthone (HM 3), 1,7-dihydroxy-2,3,4,5-tetramethoxy-xanthone (HM-4) and 1,5-dihydroxy-2,3 dimethoxy-xanthone (HM-5), were studied in rat liver microsomes in vitro. High performance liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC-ESI-IT-TOF) was applied for identification of metabolites of five xanthones mentioned above and (1)H NMR was used to elucidate the major metabolites. The structures of thirteen metabolites were identified and seven of them had not been reported before. Moreover, xanthone isomers herein could be distinguished by difference of fragmentation behaviors with increase of stages or relative abundances. The results indicated that in vitro metabolic transformation of HM-1, HM-2, HM-3, HM-4 and HM-5 occurred mainly at 2-, 4-, 5-, 7-carbonic positions on their structures of parent drugs. The metabolites could be new vasoactive substances. This work will provide a basis for study on the structure activity relationships of these xanthones and their derivatives from Tibetan herbal in the next work. PMID- 22310555 TI - The influence of social cognition on ego disturbances in patients with schizophrenia. AB - BACKGROUND: Subjects experiencing ego disturbances can be classified as a distinct subgroup of schizophrenia patients. These symptoms imply a disturbance in the ego-world boundary, which in turn implies aberrations in the perception, processing and understanding of social information. This paper provides a comparison of a group of schizophrenia patients and a group of healthy controls on a range of social-cognitive tasks. Furthermore, it analyzes the relationship between ego disturbances and social-cognitive as well as clinical variables in the schizophrenia subsample. METHODS: Two groups - 40 schizophrenia patients and 39 healthy subjects - were compared. In the source monitoring task, subjects performed simple computer mouse movements and evaluated the partially manipulated visual feedback as either self- or other-generated. In a second step, participants indicated the confidence of their decision on a 4-point rating scale. In an emotion-recognition task, subjects had to identify 6 basic emotions in the prosody of spoken sentences. In the 'reading-the-mind-in-the-eyes' test, subjects had to infer mental states from pictures that depicted others' eyes. In an attribution task, subjects were presented with descriptions of social events and asked to attribute the cause of the event either to a person, an object or a situation. Additionally, all subjects were tested for cognitive functioning levels. RESULTS: The schizophrenia patient group performed significantly worse on all social-cognitive tasks than the healthy control group. Correlation analysis showed that ego disturbances were related to deficits in person attribution and lower levels of confidence in the source monitoring task. Also, ego disturbances were related to higher PANSS positive scores and a higher number of hospitalizations. Stepwise regression analysis revealed that social-cognitive variables explained 48.0% of the variance in the ego-disturbance score and represented the best predictors for ego disturbances. One particular clinical variable, namely the number of hospitalizations, additionally explained 13.8% of the variance. CONCLUSION: Our findings suggest that ego disturbances are related to deficits in the social-cognitive domain, and, to a lesser extent, to clinical variables such as the number of hospitalizations. PMID- 22310556 TI - Liuwei Dihuang decoction facilitates the induction of long-term potentiation (LTP) in senescence accelerated mouse/prone 8 (SAMP8) hippocampal slices by inhibiting voltage-dependent calcium channels (VDCCs) and promoting N-methyl-d aspartate receptor (NMDA) receptors. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Liuwei Dihuang decoction (LW) is a typical traditional Chinese medicine (TCM) prescription and consists of six herbs including Rehmannia glutinosa Libosch. (family: Scrophulariaceae), Cornus officinalis Sieb. (family: Cornaceae), Dioscorea opposite Thunb. (family: Dioscoreaceae), Alisma orientale (G. Samuelsson) Juz (family: Alismataceae), Poria cocos (Schw.)Wolf (family: Polyporaceae) and Paeonia suffruticosa Andrews (family: Paeoniaceae). It has long been used clinically in treatment of many kinds of diseases with the sign of Yin insufficiency of kidney. AIM OF THE STUDY: Our previous pharmacological studies demonstrated that LW possesses effect of ameliorating the decline of the learning and memory in senescence accelerated mouse/prone 8 (SAMP8), but the mechanism has not been well established. LW containing serum (LWCS) is used in the current study to elucidate the possible mechanisms. MATERIALS AND METHODS: 6-month-old SAMP8 was used in this study to investigate the effect of LWCS on the induction of long-term potentiation (LTP). Primary cultured hippocampal neurons were used in this study to investigate the effects of LWCS on [Ca(2+)](i), I(Ca) and N-Methyl-d-aspartate (NMDA)-evoked currents. [Ca(2+)](i) was imaged using Fluo-3 and whole-cell patch recordings were applied to study the I(Ca) and NMDA-evoked currents. RESULTS: We find that LWCS facilitates the induction of LTP in hippocampal slices of 6-month-old SAMP8. In primary cultured hippocampal neurons, LWCS increases intracellular [Ca(2+)](i), the I(Ca) is suppressed by LWCS, and NMDA-evoked currents are promoted. CONCLUSION: These results indicate that LW improves the synaptic plasticity by inhibiting voltage-dependent calciumchannels (VDCCs) and promoting the function of NMDA receptors. This improvement might be one of the mechanisms contributing to cognitive improvement effect of LW. PMID- 22310557 TI - The anti-Candida activity of Thymbra capitata essential oil: effect upon pre formed biofilm. AB - ETHNOPHARMACOLOGICAL RELEVANCE: [corrected] Thymbra capitata essential oil is traditionally considered to exhibit powerful antiseptic properties, thus being used to treat cutaneous infections. The aim of the present study was to evaluate the effect of Thymbra capitata essential oil upon pre-formed biofilm of different Candida strains while comparing it with the activity against planktonic cells. MATERIALS AND METHODS: Fifteen Candida isolates were included, corresponding to clinical and collection type strains. Essential oil was obtained by hydrodistillation and its composition analysed by GC/MS. Activity upon planktonic cells was evaluated according to M27-A3 macromethod. Its effect upon 24h preformed biofilm biomass was determined using the crystal violet procedure and the metabolic activity was studied applying the XTT/menadione technique. RESULTS: Biofilm biomass and metabolic activity of all tested species were reduced up to 50% at MIC values. The effect was more pronounced at double MIC values, achieving >80% reduction, except for Candida albicans that presented a more resistant profile (62%). CONCLUSION: Thymbra capitata essential oil presented an important effect upon Candida biofilms. It is proposed as a valuable antifungal product to be used in an appropriate pharmaceutical formulation for the management of resistant mucocutaneous candidosis. PMID- 22310558 TI - FM-AFM imaging of a commercial polyethylene film immersed in n-dodecane. AB - The subnanometer topography of a partially crystalline polyethylene film was observed in liquid n-dodecane using a frequency-modulation atomic force microscope. Locally ordered structures were found and assigned to a (100) facet of crystalline domains. PMID- 22310559 TI - The game's afoot: seeking viruses that cause chronic and degenerative neurologic and psychiatric disorder. PMID- 22310560 TI - Effectiveness-implementation hybrid designs: combining elements of clinical effectiveness and implementation research to enhance public health impact. AB - OBJECTIVES: This study proposes methods for blending design components of clinical effectiveness and implementation research. Such blending can provide benefits over pursuing these lines of research independently; for example, more rapid translational gains, more effective implementation strategies, and more useful information for decision makers. This study proposes a "hybrid effectiveness-implementation" typology, describes a rationale for their use, outlines the design decisions that must be faced, and provides several real-world examples. RESULTS: An effectiveness-implementation hybrid design is one that takes a dual focus a priori in assessing clinical effectiveness and implementation. We propose 3 hybrid types: (1) testing effects of a clinical intervention on relevant outcomes while observing and gathering information on implementation; (2) dual testing of clinical and implementation interventions/strategies; and (3) testing of an implementation strategy while observing and gathering information on the clinical intervention's impact on relevant outcomes. CONCLUSIONS: The hybrid typology proposed herein must be considered a construct still in evolution. Although traditional clinical effectiveness and implementation trials are likely to remain the most common approach to moving a clinical intervention through from efficacy research to public health impact, judicious use of the proposed hybrid designs could speed the translation of research findings into routine practice. PMID- 22310561 TI - Caring for grieving family members: results from a national hospice survey. AB - BACKGROUND: A founding principle of hospice is that the patient and family is the unit of care; however, we lack national information on services to family members. Although Medicare certification requires bereavement services be provided, reimbursement rates are not tied to the level or quality of care; therefore, limited financial incentives exist for hospice to provide more than a minimal benefit. OBJECTIVES: To assess the scope and intensity of services provided to family members by hospice. RESEARCH DESIGN: We fielded a national survey of hospices between September 2008 and November 2009. PARTICIPANTS: A national sample of US hospices with an 84% response rate (N=591). MEASURES: Bereavement services to the family, bereavement services to the community, labor intensive family services, and comprehensive family services. RESULTS: Most hospices provided bereavement services to the family (78%) and to the community (76%), but only a minority of hospices provided labor-intensive (23%) or comprehensive (27%) services to grieving family members. Larger hospice size was positively and significantly associated with each of the 4 measures of family services. We found no significant difference in provision of bereavement services to the family, labor-intensive services, or comprehensive services by ownership type; however, nonprofit hospices were more likely than for-profit hospices to provide bereavement services to the community. CONCLUSIONS: Our results show substantial diversity in the scope and intensity of services provided to families of patients with terminal illnesses, suggesting a need for clearer guidance on what hospices should provide to exemplify best practices. Consensus within the field on more precise guidelines in this area is essential. PMID- 22310562 TI - Transplantation proceedings--a decade of evolution. PMID- 22310564 TI - Imaging evaluation of kidney using multidetector computerized tomography in living-related renal transplantation. AB - BACKGROUND: Multidetector computerized tomography (MDCT) is lesser invasive than conventional angiography and has the advantage of assessment of vessels and surrounding anatomic variants before laparoscopic nephrectomy. METHODS: From May 2005 to March 2011, 62 consecutive living kidney donors of mean age 45.3 +/- 12.7 years (range 24-70 y, male:female 26:36) underwent laparoscopic nephrectomy to paired recipients of mean age 44.8 +/- 14.0 years (range 17-74 y, male:female 38:24). The clinical characteristics and laboratory data of donors and recipients were collected for analysis. Graft function as indicated by estimated glomerular filtration rate (eGFR) was obtained from the last stable visit of the donors and the best value displayed by the recipients. RESULTS: There was no significant correlation between CT kidney volume and and eGFR. By univariate analysis, donor age was associated with worse graft function (-0.51 mL/min lower eGFR per 1 year of donor age; P < .0001). Female sex and higher effective renal plasma flow/body mass index ratio were associated with better graft function; conversely, body weight and BMI were associated with poor graft function upon univariate and multivariate analysis. An ERPF of <220 mL/min and a donor age >45 y showed significantly lower eGFR. There was no effect of CT kidney volume <100 mL. CONCLUSIONS: Our preliminary data suggest that CT kidney volume does not predict posttransplantation graft function, but MDCT is still important for analysis of anatomy before laparoscopic nephrectomy among living donors. PMID- 22310565 TI - The role of kidney biopsy to determine donation from prospective kidney donors with asymptomatic urinary abnormalities. AB - BACKGROUND: There are no definite guidelines about donation among prospective donors with asymptomatic urinary abnormalities. We evaluated the pathology of prospective kidney donors with asymptomatic urinary abnormalities and assessed the clinical outcomes of their organs. METHODS: We reviewed the medical records of 15 prospective kidney donors who underwent kidney biopsy. We evaluated the role of kidney biopsy in terms of graft function, protocol biopsy, and follow-up biopsy. We further assessed the clinical outcomes of donors and recipients. RESULTS: Thin basement membrane nephropathy (TBMN) is the most common cause of the persistent microscopic hematuria (n = 7; 50%), followed by nonspecific findings (n = 4; 29%), IgA nephropathy (n = 2; 14%), and focal segmental glomerulosclerosis (n = 1; 7%). Of the 14 candidate donors with persistent microscopic hematuria, 9 were accepted as kidney donors: 5 with TBMN, 3 with mild mesangiopathy, and 1 with nonspecific interstitial changes. The function of the 9 grafts was relatively stable (mean serum creatinine level 2.38 mg/dL) over a mean follow-up of 57 months. Graft failure that developed in 2 grafts was not associated with biopsy findings: acute rejection and patient death with a functioning graft. Interestingly, basement membrane thickness in 2 allografts from donors with TBMN appeared normal by electron microscopy follow-up biopsy; the allografts did not show hematuria. Moreover, the clinical outcomes of donors were favorable (mean serum creatinine 0.94 +/- 0.32 mg/dL) during the mean follow up period of 34.7 +/- 42.5 months. We did not observe new-onset hypertension or proteinuria in donors. CONCLUSIONS: Kidney biopsy in prospective kidney donors with urinary abnormalities is a safe and effective diagnostic procedure to stratify candidates. Therefore, kidney biopsy should be actively performed to improve the prognosis of both donors and recipients. PMID- 22310566 TI - The utilization and advantages of an exchange donor program in living donor renal transplantation: a single-center experience. AB - INTRODUCTION: The availability of donors is a major limiting factor in living donor renal transplantation. Approximately one third of patients with end-stage renal disease have willing potential living donors who are blood type or cross match incompatible. The living donor kidney exchange has become an efficient solution for recipients in this situation. We analyzed the outcome and advantages of an exchange donor program compared with ABO-incompatible transplantation and desensitized protocol transplantation for highly sensitized patients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 152 exchange donor cases from 1991 to 2010. We analyzed the risk factors, outcomes, matching factors, complication rates, and acute rejection rates of this program compared with other alternative strategies. RESULTS: In our center, 22% of total living donor kidney transplantations were performed through an exchange program and an expanded donor pool. The graft survival, complication, and acute rejection rates were not significantly different compared with the alternatives. The severe complication rates were lower than with the alternatives and the immunosuppressant protocol and preoperative preparation were simpler. Blood type O recipients who registered in the exchange program showed no significant differences from the living related groups (P = .45), which were similar to the proportions for other ABO types. Upon multivariate analysis, an acute rejection episode and use of mycophenolate mofetil (MMF) were significant factors associated with graft survival (P = .015 and P = .007; odds ratio [OR] 5.968 and 7.324; 95% confidence interval [CI] .003-.533 and .098-.690). CONCLUSION: Although exchange donor programs are not the sole solution, they show several advantages, such as the prescription of standard immunosuppression, simple preoperative preparation, low cost, and modest rates of severe complications compared with ABO-incompatible transplantation or desensitized protocols. PMID- 22310567 TI - The role of the altruistic unbalanced chain in exchange living donor renal transplantation: single-center experience. AB - BACKGROUND: The exchange donor program in renal transplantation is an efficient solution for recipients with a blood type or crossmatch-incompatible donor. However, this program has some difficulties to define unacceptable human leukocyte antigen matches, deteriorating clinical potential recipient condition, and withdrawal of donor consent. We analyzed the outcomes of exchange donor renal transplantation through the altruistic unbalanced chain. METHODS: Among 152 cases of exchange donor renal transplantation from 1991 to 2010 in our hospital, we performed 58 procedures through altruistic unbalanced chains. We compared their outcomes with the direct and balanced chain group. We analyzed retrospectively whether this program expanded the donor pool, seeking better immunologic, size, and age matching. RESULTS: The graft survival and acute rejection rates did not differ significantly in the two groups. Of 152 cases, 58 (38.2%) renal transplantations were performed through an unbalanced chain. Seventeen waiting list recipients were transplanted through an altruistic unbalanced chain. In blood type O recipients (n = 32), the causes of registration in the exchange program were ABO incompatibility (93.3%), and positive crossmatch (6.7%). Nine altruistic blood type O donors and 9 (28.1%) type O recipients underwent transplantations through this chain. CONCLUSIONS: We suggest the altruistic unbalanced chain may expand the donor pool with advantages for difficult-to-match pairs. The disadvantages of type O recipients may be overcome through the use of an unbalanced chain. The altruistic unbalanced exchange transplantation program can help easy-to-match subjects, shortening the waiting periods. PMID- 22310568 TI - Comparative outcomes of open nephrectomy, hand-assisted laparoscopic nephrectomy, and full laparoscopic nephrectomy for living donors. AB - OBJECTIVE: Kidney transplantation is a standard treatment for end-stage renal disease. There are many methods of harvesting kidneys from living donors. At present, the role of minimally invasive surgery, including hand-assisted and full laparoscopic nephrectomy, is well established and tends to replace open surgery at many institutions. We conducted a retrospective study to compare the outcomes of these operative procedures at Ramathibodi Hospital in Bangkok. MATERIALS AND METHODS: We retrospectively reviewed 200 patients who underwent open nephrectomy (ON), hand-assisted laparoscopic nephrectomy (HALN), and full laparoscopic nephrectomy (FLN) between January 2006 and November 2010. Demographic data, type of surgical procedure, operative time, warm ischemic time (WIT), length of hospital stay (LOH), estimated blood loss (EBL), analgesic use, and complications from surgery were recorded. Results were compared using a one-way analysis of variance in order to determine differences. RESULTS: During the study period, 200 living kidney donors underwent nephrectomy. Of these, 95 (47.5%) received ON, 23 (11.5%) received HALN, and 82 (41%) received FLN. The operative time for the patients who underwent HALN and FLN was statistically significantly longer than that of the patients who underwent ON. On the other hand, the EBL for the ON group was significantly greater than for the HALN and FLN groups. The WIT was shortest for the ON group, followed by the HALN and FLN groups. The LOH did not differ among the three groups. Analgesic use was significantly higher in the ON group. Surgical complications were identified in 24 patients (12%). CONCLUSION: Our results show that laparoscopic living donor nephrectomy is a relatively safe procedure when performed by experienced surgeons at appropriate institutions. Though the operative times and WITs were slightly longer and the cost was higher for the laparoscopic groups, the EBL was lower and the pain score was lower. Indeed, laparoscopic living donor nephrectomy is an attractive alternative surgical procedure. However, there is a long learning curve and experienced surgeons are required. PMID- 22310569 TI - Hand-assisted technique facilitates preserving graft viability in laparoscopic donor nephrectomy. AB - BACKGROUND: To achieve patient safety and minimal operative invasion in living kidney donor nephrectomy, we have performed hand-assisted laparoscopic donor nephrectomy (HALDoN) since 2006. AIM: The aim of this study was to evaluate the utility and the technique of HALDoN. METHOD: We analyzed 72 donors who underwent HALDoN from February 2008-August 2011. RESULTS: Including 8/72 donors who underwent right nephrectomy, all subjects completed HALDoN without conversion to an open procedure. None of the recipients suffered delayed graft function or an ureteric problem. Knife-to-removal time (KRT) was longer among cases with graft weight (GW) >200 g than GW <=200 g: 176.5 +/- 35.1 minutes vs 142 +/- 18.7 minutes (P < .001). Longer KRT (>180 minutes) and right nephrectomy produced longer reperfusion-to-urine secretion time (RUT; P = .002 and P = .027, respectively). Grafts with double renal arteries (N = 10) also tended to show longer RUT (P = .058). In a case with an early renal arterial branch <1 cm from the aorta, we transected the vessel to achieve a single orifice of the artery using a stapling device. At 6 months the average value of decreased renal function of donors had recovered to about 70%. The incidence of complication was 8.3% but there was no life-threatening morbidity. CONCLUSION: The hand-assisted method could make the operating surgeon more confident to perform laparoscopic donor nephrectomy safely. HALDoN offers particular advantages for precise dissection using finger retraction and control of potential bleeding in the stages of vascular stapling and graft removal, preserving graft viability. PMID- 22310570 TI - Laparoscopic donor nephrectomy: single-center experience. AB - OBJECTIVE: Laparoscopic living donor nephrectomy (LLDN) has become the standard procedure for renal transplantation. This technique is considered less invasive for the donor, allowing lower postoperative analgesic requirements and a faster return to daily activities. In Japan, 1123 renal transplantation were performed in 2009. And, almost 83% were living related procedures. The aim of this study was a retrospective assessment of the safety and outcomes of LLDN on renal transplantations. MATERIAL AND METHODS: We retrospectively analyzed the intraoperative data and surgical complications for 21 patients who underwent retroperitoneoscopic living donor nephrectomy between June 2009 and March 2011. RESULTS: LLDN was successfully completed in all patients, without conversion to open surgery. Mean operative time was 243.5 +/- 46.0 minutes with an average blood loss of 46.0 +/- 46.1 mL. Warm ischemic time was 2.1 +/- 0.62 minutes. Hospital stay was 11.1 +/- 2.7 days. There were no major donor complications. One patient presented a wound infection responding to conservative treatment. CONCLUSIONS: LLDN is a safe effective procedure. The vascular stapler is useful to manage the renal vessels. PMID- 22310571 TI - Does video-assisted minilaparotomy surgical living donor nephrectomy satisfy donors? AB - PURPOSE: Video-assisted minilaparotomy surgical (VAMS) nephrectomy is believed to provide better cosmetic outcomes than open-donor nephrectomy in healthy donors. However, the results of a few studies have influenced the opinion of donors on their physical appearance. This study investigated the satisfaction of donors after a VAMS living donor nephrectomy. METHODS: Donors who underwent VAMS living donor nephrectomy between 2009 and 2011 were requested to fill out a body image questionnaire. This questionnaire consisted of three subscales: body image scale (BS), confidence in surgery scale (CS), and hospital experience scale (HS). A total of 20 VAMS living nephrectomy donors completed the questionnaire. RESULTS: The study included 3 male and 17 female donors of overall mean age of 38.7 +/- 12.4 years. Eight donors were unmarried (40.0%), 11 were married (55.0%), and 1 was divorced. The mean follow-up was 7.9 +/- 4.5 months. The mean BS, CS, and HS scores were 41.6 +/- 5.3, 21.85 +/- 8.3, and 13.9 +/- 2.2, corresponding to perfect scores of 50, 30, and 20, respectively. CONCLUSION: The results of this study showed that VAMS nephrectomy donors tended to be pleased with their body image, operation, and hospital experiences. PMID- 22310572 TI - Kidney grafts with multiple renal arteries is no longer a relative contraindication with advance in surgical techniques of laparoscopic donor nephrectomy. AB - OBJECTIVES: Kidney grafts with multiple renal arteries were considered as a relative contraindication. We retrospectively reviewed our experience of kidney grafts with multiple renal arteries to clarify the usefulness of these grafts. METHODS: Between September 2002 and June 2011, 100 laparoscopic donor nephrectomies (LDNs) were performed consecutively. Three-dimensional computed tomographic angiography was routinely performed preoperatively. Donor demographics, operative characteristics, donor and recipients perioperative complications, and donor and recipient outcomes were reviewed retrospectively. RESULTS: Eighty-nine donors had single (group A1) and 11 donors had multiple renal arteries (group B1). Multiple arteries caused by application of the vascular stapler were found in another six donors. Overall, 17 kidney grafts required bench arterial reconstruction (group B2). The other 83 donors with single renal artery did not require further arterial reconstruction (group A2). There was a significant increase of warm ischemic time in the group of multiple renal arteries. There were no significant difference between groups A1 and B1 in regard to donor demographics, operative characteristics, and donor outcome. Kidney grafts requiring vascular reconstruction experienced equal immediate and long-term allograft outcomes with those of group A2. The actuarial 1-, 3-, and 5 year allograft survival rates were also comparable in both groups (95.4%, 92.6%, 92.6% in group A2 and 100%, 100%, 100% in group B2). CONCLUSION: LDN in the presence of multiple renal arteries is feasible and safe. Both immediate and long term allograft outcomes are comparable between kidney grafts with and without vascular reconstruction. Kidney grafts with multiple renal arteries are no longer a relative contraindication with advanced LDN surgical techniques. PMID- 22310573 TI - Long-term outcomes of living kidney donors over the past 28 years in a single center in Taiwan. AB - BACKGROUND: The chronic shortage of kidneys for transplantation has increased the number of living donations, but demand remains high, which has created a long waiting list of end-stage kidney disease patients. Donors with decreased renal mass may suffer a higher risk of developing proteinuria, hypertension (HTN), and chronic renal disease (CKD) during long-term follow-up. METHODS: We retrospectively retrieved medical data of living kidney donors at our hospital over the past 28 years. RESULTS: There were 45 male and 60 female donors with a mean donation age of 46.34 +/- 12.47 years (range = 20-70y). The mean follow-up duration was 4.67 +/- 4.78 years. The serum creatinine (Cr) at donation was 0.93 +/- 0.22 mg/dL, while the latest Cr was 1.26 +/- 0.45 mg/dL (P < .001). The mean age at follow-up was 50.95 +/- 14.57 years. At last follow-up, eight subjects (7.6%) displayed HTN requiring treatment, 10 (9.5%), proteinuria and 55.4%, an estimated glomerular filtration rate (eGFR) of less than 60 mL/min, including one with diabetic nephropathy at 10 years after donation who required long-term hemodialysis. Although gender did not correlate with occurrence of HTN, proteinuria, and CKD, the occurrence of CKD was associated with age at donation (P < .001, odds ratio [OR] = 1.076), and age at follow-up (P < .001, OR = 1.071). HTN donors were older (P = .036, OR = 1.057) with longer follow-up durations (P = .007, OR = 1.166) and had higher Cr values at donation (P = .044, OR = 94.4). Donors with proteinuria were not related to gender, follow-up duration, initial Cr, warm ischemic time, or duration of admission. eGFR was indeed worse after donation (P = .002). CONCLUSIONS: Our results indicated a significant proportion of living donors may develop CKD upon long-term follow-up. The factors affecting donor risk of CKD were baseline renal function, older age, and duration after kidney donation. PMID- 22310574 TI - Delayed graft function in living-donor renal transplantation: 10-year experience. AB - BACKGROUND: Delayed graft function (DGF), a dialysis requirement within a week after transplantation, can occur in deceased-donor renal transplantation. DGF is rare, in living-donor renal transplantation (LDRT) and its incidence and risk factors have not been established. METHODS: We investigated the incidence and clinical characteristics of DGF in LDRT over 10 years. We compared HLA mismatches, panel reactive antibody status, frequency of nonrelated donors, donor age, sex match, recipient-donor body weight ratio, total ischemia time, and transplanted kidney weight between DGF and non-DGF patients. RESULTS: The incidence of DGF in LDRT was 1.6%, which differed from earlier reports. HLA mismatch, female recipient frequency, and nonrelated donors were higher among the DGF group, but no risk factor for DGF was significant after multivariate logistic regression analysis. Biopsy findings showed 2 cases to be associated with rejection, 1 with acute pyelonephritis and 1 with acute tubular necrosis. The cases with rejection resulted in graft failure within 3 years after transplantation, but the other cases were followed with favorable graft function. CONCLUSIONS: The incidence of DGF among LDRT was lower than that reported earlier studies, and the factors previously reported to cause DGF were not associated with DGF herein. Because DGF with rejection responses has a poor prognosis, strenuous strategies, including biopsy, should be performed in cases of DGF after LDRT. PMID- 22310575 TI - World kidney day 2010: medical aspects of 10 live-donor renal transplantations in a single center from a developing country. AB - BACKGROUND: World Kidney Day (WKD) has become the most widely celebrated event associated with kidney disease in the world and the most successful effort to raise awareness among both the general public and government health officials about the dangers of kidney disease. We celebrated WKD 2010 in a unique way by performing 10 live-donor renal transplantations (RTx) on March 11, 2010. PATIENTS AND METHODS: We report a single-center experience on RTx vis-a-vis patient/graft survival, graft function in terms of serum creatinine (SCr) level, and rejection episodes in 10 live-donor RTx performed on WKD. Recipient diseases leading to end stage renal disease (ESRD) were chronic glomerulonephritis (60%), benign nephrosclerosis (20%), and chronic interstitial nephritis (20%). Mean recipient age was 35 +/- 8.7 years. Nine recipients were males. Mean donor age was 37 +/- 8.7 years, Nine donors were females. Donors were spouse (n = 6), mother (n = 2), sister (n = 1), and extended family member (n = 1), with mean HLA match 1.8 +/- 1.48. All patients received steroids, calcinueurin inhibitors, and mycophenolate mofetil/azathioprime for maintenance immunosuppression. RESULTS: During a mean follow-up time of 18 months, patient and graft survival rates were 90% and 90%, respectively, with a mean SCr level of 1.21 mg/dL; 20% had biopsy-proven acute rejection. One patient died due to infection after antirejection therapy. CONCLUSION: RTx has acceptable graft and patient survival. RTx is the best cost effective therapeutic modality for patients suffering from ESRD and should be encouraged in view of organ shortage on events such as WKD. To our knowledge, this is the first report from a developing country on 10 successful RTx on WKD. PMID- 22310576 TI - (99m)Tc-mercaptoacetyl triglycine renography to monitor renal transplant function among kidneys from donors after cardiac death. AB - PURPOSE: Delayed graft function usually occurs after kidney transplantation from donors after cardiac death, It is important to monitor graft function during the anuric period, but there have been few useful tools. Consequently, we evaluated the availability of (99m)-Tc mercaptoacetyltriglycine (MAG3) renography. METHODS: Thirty-two patients underwent renal transplantation from donors after cardiac death between June 2, 2005, and April 14, 2011. One patient was excluded due to an acute rejection episode which developed during the dialysis period. The first (99m)Tc-MAG3 renogram was performed as early as possible after the operation and repeated until the patient was weaned from dialysis. The corrected tubular extraction rate (cTER; mL/min/1.73 m(2)) was calculated; it represents the MAG3 clearance corrected by body surface area. RESULTS: cTER was low immediately after transplantation, but increased gradually until the patient was weaned from dialysis. A significant correlation was observed between early cTER and the period of dialysis-dependence (r = -0.677, P < .001) as well as the short-term best corrected creatinine clearance (r = 0.526, P = .002). CONCLUSION: We observed that graft function can be monitored by routinely performing (99m)Tc MAG3 renography after transplantation of kidneys from donors after cardiac death. PMID- 22310577 TI - Kidney transplantation using expanded criteria donors in Korea. AB - BACKGROUND: Use of expanded criteria donor (ECD) grafts seeks to solve the organ shortage. We investigated the current status of donor selection and transplantation outcomes. METHODS: We retrospectively analyzed 791 kidney transplantations performed between 1997 and 2009. An expanded criteria deceased donor (ECDD) was defined as an individual who fulfilled the United Network for Organ Sharing criteria or, the Nyberg criteria. An expanded criteria living donor (ECLD) was determined by fulfillment of 1 or more of 5 criteria. RESULTS: Deceased and living donor kidney transplantations were performed in 228 (28.8%) and 563 (71.2%) cases, respectively. Forty-three cases (18.9%) belonged to the ECDDs. The ECDD group showed a lower posttransplantation 1-year estimated glomerular filtration rate (eGFR) than that of the standard criteria deceased donor (SCDD) group (70.7 +/- 19.2 vs 48.6 +/- 11.5; P < .001). The ECDDs were allocated to older recipients or recipients with more HLA mismatches than SCDDs. The number of ECLD cases was 173 (30.7%). The proportions of each medical abnormality of living donors were as follows: age older than 60 years (0.5%), hypertension (2.5%), obesity (2.1%), low eGFR (25.9%), proteinuria (0%), and microscopic hematuria (1.4%). The ECLD group showed a lower posttransplantation 1 year eGFR than that of the standard criteria living donor (SCLD) group (66.9 +/- 16.0 vs 58.3 +/- 11.2; P < .001). Graft survival was not different among the donor types (P = .518). CONCLUSIONS: eCDs were 27.3% of the total kidney donors. Posttransplantation 1-year eGFR was lower in the ECD group. However, there was no difference in the graft survival among the different donor types. PMID- 22310578 TI - Adult dual kidney transplantations obtained from marginal donors: two case reports. AB - Organ shortage has led us to use grafts from expanded criteria donors (ECD). Dual kidney transplantation (DKT) using organs from an ECD, which are not acceptable for single kidney transplantation (KT), may overcome the insufficient functioning nephron mass. We performed DKTs in two recipients, the first DKT to be reported from Korea. In case 1, the donor was a 36-year-old man with hypertension. The cause of his brain death was intracranial hemorrhage. He had no known underlying renal disease; his serum creatinine level was 4.2 mg/dL. Despite the relatively young age of the donor, a biopsy revealed mild interstitial fibrosis and tubular atrophy with moderate arteriolar narrowing. The recipient's postoperative course was uneventful over the 69-month follow-up; her last serum creatinine was 1.3 mg/dL. In case 2, the 80-year-old male donor with a history of hypertension had a normal creatinine. The donor biopsy revealed mild glomerular sclerosis, tubular atrophy, and interstitial fibrosis with moderate arteriolar narrowing. The recipient had undergone a previous KT 14 years previously on the right side of the abdomen, but had resumed dialysis 2 years previously due to chronic allograft nephropathy. There was no delayed graft function. At month 4 posttransplantation, lymphoceles were treated by fenestration. At 6-month follow-up, her creatinine was 1.0 mg/dL. In our experience with these two cases, DKT with ECD kidney grafts seemed to be a successful strategy to avoid poor graft outcomes and overcome the donor organ shortage. Further studies including histological criteria for DKT, should be performed to determine the safest means to utilize ECD grafts. PMID- 22310579 TI - Desensitizing the broadly human leukocyte antigen-sensitized patient awaiting deceased donor kidney transplantation. AB - For broadly human leukocyte antigen-sensitized patients (HS; calculated panel reactive antibody >80%), options for deceased donor (DD) transplantation are extremely limited. Data from United Network for Organ Sharing (2000-2009) indicate that <10% of HS patients are transplanted each year. Immune modulation of HS patients using intravenous immunoglobulin (IVIG) and rituximab has shown promise in reducing donor-specific antibody (DSA) titers and improving the chances for successful transplantation for patients awaiting DD transplants. Critical to the success of desensitization with IVIG + rituximab is a coherent antibody-testing strategy aimed at detection of DSA reductions and identification of crossmatch parameters that are associated with a low likelihood of antibody mediated rejection posttransplant. Here, we discuss data that examine the efficacy of IVIG + rituximab in reducing DSA levels and improving chances for a successful DD transplantation. Patient and graft survival data are also presented as is an analysis of the safety of IVIG + rituximab in sensitized patients. PMID- 22310580 TI - Cytotoxic flow cytometric crossmatch in renal transplantation: a single assay to simultaneously detect antibody binding and cytotoxicity. AB - OBJECTIVES: The complement-dependent lymphocytotoxicity crossmatch (CDC-XM) detects cytotoxic parameters of preformed antibodies. The flow cytometric crossmatch (FCXM) is used to detect the binding of recipient antibodies to donor cells. Because these two assays provide different information, both methods are often performed to assess the compatibility of donor-recipient pairs. The aim of this study was to develop a single assay that can simultaneously detect antibody binding and cytotoxicity. METHODS: A procedure called cytotoxic flow cytometric crossmatch (cFCXM) that determines cell death and antibody binding simultaneously was developed. The assay was validated in parallel with extended incubation CDC XM. Receiver operating characteristic analysis was used to determine the cut-off level. Furthermore, pretransplantation sera from seven recipients with pretransplantation donor-specific antibodies (DSA) and negative CDC-XM were retrospectively tested for cFCXM (4 without antibody-mediated rejection (AMR) and three with AMR). RESULTS: The optimal method for the simultaneous detection of antibody binding and cytotoxicity in a single assay has been determined. Four of four patients (100%) with pretransplantation DSA and without AMR had negative cFCXM in both parameters. Of three patients with pretransplantation DSA who developed AMR, two patients (66.7%) had positive B-cell cFCXM in both parameters, and 1 patient (33.3%) had positive T-cell cFCXM in a binding parameter only. The first patient had anti-DR9, DR53, DQ9, the second patient had anti-A11, DR12 and the last one had an anti-B46 in their pretransplantation sera. These 3 cases experienced biopsy-proven AMR after living-donor kidney transplantation. CONCLUSION: The newly developed assay, cFCXM, can simultaneously determine cytoxicity and antibody binding using a single platform. Furthermore, this assay can detect clinically significant HLA alloantibodies undetectable by conventional crossmatches. The cFCXM could serve as a new tool for the detection of a recipient's alloantibodies. PMID- 22310581 TI - Management of patients on the waiting list for deceased donor kidney transplantation. AB - BACKGROUND: Although the number of wait-listed patients for deceased donor kidney transplantation has been continuously increasing in Korea, no standard guidelines exist for their management. METHODS: We retrospectively analyzed the medical records of our 1,231 wait-listed patients between 2000 and 2010. RESULTS: The time to transplantation of the 201 recipients was 51.9 +/- 31.2 months. Ninety seven patients died while waiting. Diabetic or older patients have increased among new registrants; however, <50% of them have undergone regular screening for malignancy or cardiovascular diseases. Patients with regular screening were more likely to get a chance to receive a transplant (P = .016). Malignancy was newly diagnosed in 26 patients (2.1%) and reversible cardiac ischemia was detected in 9.7%. The presence of anti-HLA antibodies was strongly associated with a lower transplantation rate, whereas blood type O was not. Although use of expanded criteria donor (ECD) kidneys increased, many patients avoided them. CONCLUSION: It is necessary to improve management programs for wait-listed patients by establishing comorbidity screening and ECD education. PMID- 22310582 TI - Clinical outcome of renal transplantation in end-stage renal disease patients with positive pretransplantation hepatitis B surface antigen. AB - BACKGROUND: Renal transplantation (RTx) is the best therapeutic modality for patient suffering from end-stage renal disease (ESRD) with positive pretransplantation hepatitis B surface antigen (HbsAg). We report 11 years of single-center experience on RTx vis-a-vis patient/graft survival, graft function in terms of serum creatinine (SCr), and rejection episodes in 35 ESRD patients with pretransplantation HbsAg positivity. PATIENTS AND METHODS: Thirty-five ESRD patients with pretransplantation HbsAg positivity underwent RTx at our center between 2000 and 2010. Mean recipient age was 36.06 +/- 12.22 years; 30 were males and 5 were females. Mean donor age was 43.51 +/- 13.63 years; 13 were males and 22 were females. The majority of donors were parents (31.42%) and spouses (22.85%). Mean HLA match was 2 +/- 1.37. The most common recipient diseases leading to ESRD were chronic glomerulonephritis (51%) and diabetes (17.5%). Posttransplantation immunosuppression consisted of a calcineurin inhibitor-based regimen. RESULTS: Over mean follow-up of 6.16 +/- 3.69 years, patient and graft survival rates were 71.42% and 71.42%, respectively, with mean SCr of 1.92 +/- 0.62 mg% with 20% biopsy-proven acute rejection episodes. In total, 10 (28.57%) patients were lost, mainly to infections. CONCLUSION: RTx for ESRD with pretransplantation HbsAg positivity has acceptable graft function and patient/graft survival over 11 years follow-up and should be encouraged. PMID- 22310583 TI - Kidney transplantation in patients with long-term (more than 15 years) prior dialysis therapy. AB - OBJECTIVE: The number of kidney transplantations (KTx) among patients on long term hemodialysis (HD) is increasing due to the donor shortage in Japan. We investigated the outcomes of KTx among long-term (more than 15 years) patients on HD. METHODS: We performed 103 KTx between April 2003 and April 2010 including seven patients (one living and six deceased donor grafts), who had been treated with HD for more than 15 years (group 1) compared with 96 patients (94 living and two deceased donor grafts) treated for less than 15 years (group 2) before KTx. We examined the differences in patient and graft survivals and complication rates between the groups. RESULTS: Acute rejection episodes (ARE) occurred in 2 (29%) group 1 and 22 (22%) group 2 subjects. Urinary tract infections were diagnosed in 1 (14%) group 1 versus 8 (8%) group 2 cases. The incidence of perioperative complications, such as delayed graft function, cytomegalovirus infection, and surgical complications was higher among group 1. The serum creatinine at 1 year after KTx was the same (1.3 mg/dL). The patient/graft survivals were 100%/100% at 1 and 3 years in group 1 versus 100%/100% at 1 and 99%/98% at 3 years in group 2. CONCLUSION: The outcomes of KTx among long-term dialysis patients were similar to those in short-term dialysis patients. PMID- 22310584 TI - Outcomes of renal transplantation after end-stage renal disease due to diabetic nephropathy: a single-center experience. AB - BACKGROUND: Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) worldwide. However, data on renal transplantation outcomes in diabetic nephropathy among Japanese remain inadequate. This retrospective study was conducted to summarize our renal transplantation experience in diabetic ESRD patients. METHODS: We retrospectively studied 462 patients who underwent kidney transplantation between 1989 and 2011, including 23 with diabetic ESRD (DM group) and 439 with nondiabetic ESRD (NDM group). We compared demographic and clinical variables between these 2 groups. RESULTS: Mean age was higher in the DM group (48.0 vs 38.2 years; P < .001), and there was no significant difference in gender or donor source. The 1-, 3-, and 5-year graft survival rates in the DM and NDM groups were 100% vs 98.3% (ns), 82.4% vs 94.9% (P < .05), and 66.7% vs 90.3% (P < .01), respectively. The 1-, 3-, and 5-year patient survival rates were 95.0% vs 96.5% (ns), 88.2% vs 95.2% (ns), and 84.6% vs 92.9% (ns), respectively. One patient (4.3%) in the DM group and 6 (1.4%) in the NDM group died from cardiovascular disease during the follow-up period (ns). The incidence of rejection did not differ between the DM and NDM groups. There were no significant differences in the total infection rate or the urinary tract infection rate. CONCLUSIONS: Renal transplantation in diabetic ESRD patients yields good results in terms of patient survival and complications, suggesting that renal transplantation can be performed in these patients and should become a more established treatment option. PMID- 22310585 TI - Follow-up and treatment of renal transplantation with nephropathic cystinosis in central Taiwan. AB - BACKGROUND: Cystinosis is a rare autosomal recessive disease caused by a defect in lysosomal cystine. The intracellular cystine accumulation causes damage in multiple organs and renal failure. We retrospectively evaluated the outcomes and complications of patients with nephropathic cystinosis after renal transplantation (RT) in Taiwan. METHODS: Only 2 nephropathic cystinosis patients (siblings) had RT out of the 1,196 RTs in our hospital over the past 30 years. The younger sister received a living-related RT from her mother. The elder sister received a second cadaveric RT owing to chronic allograft rejection one-half year before. RESULTS: They were diagnosed with cystinosis at ages 5 and 9 years, and received allografts at ages 13.4 (younger) and 19.8 and 26.4 (elder) years. They each experienced 1 episode of acute rejection at 6 months after the first RT. The elder sister suffered from obstructive nephropathy with progressive graft failure at age 26.4 years and was treated for vulvar condyloma and carcinoma in situ of cervix. The second graft kidney then maintained good kidney function. The younger sister delivered a girl without complication during gestation, and her renal function also remained good. At latest follow-up, they both had crystalline keratopathy and nephropathy, but no other system involvement. CONCLUSIONS: The extrarenal complications with nephropathic cystinosis are high. These 2 siblings had only have ocular involvement without further cysteamine therapy. However, long-term follow-up is required to monitor development of complications and determine their prognoses. PMID- 22310586 TI - Renal transplantation in patients with human T-cell lymphotropic virus type 1. AB - BACKGROUND: Renal transplantation (RTx) in carriers of human T-cell lymphotropic virus type 1 (HTLV-1) has a risk of developing overt leukemia upon immunosuppression. Although there have been a few reports of such cases, it is unclear HTLV-1 carrier if patients on the modern immunosuppressants would develop HTLV-1-associated myelopathy or adult T-cell leukemia lymphoma. METHODS: We retrospectively reviewed the clinical outcomes of RTx in nine HTLV-1 carriers to assess a risk of developing leukemia from 2002 to 2011 using immunosuppression with a calcineurin inhibitor, mycophenolate mofetil (MMF), and steroid. The anti CD25 monoclonal antibody basiliximab was used for induction. In two cases of ABO incompatible RTx, the rituximab was also administered before RTx. RESULTS: The ratio of male to female subjects was 2 to 7 with an overall mean recipient age of 54.3 +/- 8.1 years. We prescribed cyclosporine (n = 5) or tacrolimus (n = 4). There was only one graft loss due to the death caused by aspiration pneumonia with a functioning graft. No one developed overt leukemia with combined treatment with MMF, basiliximab and rituximab. CONCLUSION: We concluded that RTx in HTLV-1 carriers could be performed using a modern immunosuppressive regimen, without the risk of developing leukemia. PMID- 22310587 TI - Frequent false-positive reactions in pronase-treated T-cell flow cytometric cross match tests. AB - OBJECTIVE: Pretransplantation cross-match (XM) is essential in organ transplantation. The flow cytometric XM (FCXM) is the most sensitive cell-based XM technique. Pronase treatment is used to improve the sensitivity and specificity of the B-cell FCXM. Thus, pronase-treated (PT) T cells are tested in a single tube T-cell/B-cell technique. Observing discrepancies between PT and pronase-nontreated (PN) T- FCXM results, we investigated their incidence, clinical significance, and possible causes. METHODS: We tested 226 serum samples from 167 kidney transplantation candidates or posttransplantation follow-up patients using PT and PN T-FCXM in parallel using 3-color and 2-color immunofluorescence staining, respectively. We reviewed panel-reactive antibody (PRA) and donor-specific antibody (DSA) status as well as HLA data and clinical outcomes. RESULTS: The T-FCXM positive rate was significantly higher among PT versus PN tests (24.3% vs 11.1%; P < .001). Less than half of the PT-positive cases were positive in the PN test (45.5%; 25/55). Discrepancies were observed in 30 cases (13.3%), all of which gave PT(+)/PN(-) results. Our findings suggested that PT(+)/PN(-) results might arise from non-HLA antibodies. Class I DSA positive rate (6.3% vs 2.2%; P = .45) and antibody-mediated rejection rate (0% vs 16.3%; P = .32) were not different between PT(+)/PN(-) and PT(-)/PN(-) groups. Moreover, 2 cases of PT(+)/PN(-) were observed among HLA-A, B, DR-identical donor recipient pairs. CONCLUSION: Pronase treatment is prone to give false-positive reactions in T-FCXM test probably due to the participation of non-HLA antibodies including autoantibodies. Patients might be inappropriately excluded from receiving organs. In laboratories using PT single tube T/B FCXM, caution is needed to avoid false-positive reporting of results. PMID- 22310588 TI - Renal replacement therapy: available information versus demands of patients. AB - OBJECTIVE: This study examined the current state of information on renal replacement therapy and the educational demands of kidney transplant recipients. METHODS: The study was conducted through a survey. The questionnaire of this study was developed by researchers and was completed by 72 kidney recipients. RESULTS: The recipients were most frequently informed of hemodialysis (87.5%), followed by kidney transplantation (69.4%) or peritoneal dialysis (48.6%) as a modality of renal replacement therapy at the time of diagnosis of chronic renal failure. Information about kidney transplantation was provided when they were diagnosed with end-stage renal disease (ESRD; 33.3%) or right after initiation of dialysis (15.3%) or a few years thereafter (9.7%). They were informed about kidney transplantation mostly by transplantation surgeons (mean degree score = 3.1 +/- 1.3; range, 1-4), followed in order by transplant coordinators, nephrologists, family members, other patients, artificial kidney unit nurses, and mass media or internet. Regarding the influence of the information on their decision to receive a transplant, the mean score was 3.2 +/- 1.2 (range, 1-5). Also, kidney transplantation was evaluated as the best renal replacement therapy for work, pregnancy/delivery, traveling, and diet. CONCLUSION: Patients diagnosed with ESRD are not fully informed of transplantation as a primary optimal renal replacement therapy for their quality of life. PMID- 22310589 TI - Cyclosporine microemulsion formulation (sigmasporin microral) effect as first line immunosuppressant on renal functions at 3 years. AB - BACKGROUND: Cyclosporine (CsA) remains a mainstay of immunosuppressive maintenance regimens in developing countries, but its effects on long-term kidney allograft survival are still unclear. Our aim was to assess a generic microemulsion CsA (Sigmasporin) for long-term impact on graft function and patient survival among stable renal transplant patients. METHODS: Over a 36-month period, patients with transplantations from >6 months earlier were maintained on CsA doses of 2-8 mg/kg/d to keep C(2) within the recommended therapeutic range. We assessed 25 efficacy and tolerability parameters of scheduled intervals. RESULTS: Twenty-seven patients (9 female, 18 male) from 6 centers in 4 Middle Eastern countries were enrolled between 2004 and 2009. Their average age was 35.1 +/- 9.8 years, body mass index ranged from 15.7 to 41.2 kg/m(2), and average time from transplantation was 2.2 +/- 1.6 years. Within the 36-month observation period the CsA dose was reduced by 17.3% from 2.89 +/- 0.88 mg/kg/d to achieve C(2) levels of 600-1000 ng/mL. After 36 months the glomerular filtration rate declined by 8.2% from an overall baseline mean of 72.7 +/- 23.5 mL/min/1.73 m(2). It improved in 11.1% of patients and remained unchanged in 44.4%. No new cases of hypertension or diabetes mellitus were reported, and there was 1 case of borderline hyperlipidemia. Graft functions were stable, apart from 2 incidences of CsA nephrotoxicity. Both graft and patient 3-year survival rates were 100%. CONCLUSIONS: On a 3-year basis, Sigmasporin Microral was effective to maintain stable renal functions in kidney transplant patients, with safety and tolerability profiles similar to those reported in the international literature. PMID- 22310590 TI - Safety and efficacy of generic cyclosporine arpimune in Filipino low-risk primary kidney transplant recipients. AB - BACKGROUND: In the Philippines, maintenance of immunosuppression may not always be affordable, leading to acute rejection and graft loss. The availability of the generic cyclosporine Arpimune could be economically beneficial, but its safety and efficacy should be established. METHODS: This prospective cohort study enrolled 30 renal transplant patients who received Arpimune with mycophenolate/prednisone. Their results were compared up to 6 months with 30 matched control patients who received Neoral during the same period. Areas under the receiver operating characteristic curves (AUC) after intake of Arpimune and therapeutic drug monitoring using cyclosporine levels 2 hours after each dose were done. Pearson correlation was performed to determine linearity of relationship between the generic cyclosporine concentrations and AUC 0-4. Chi square test was used in obtaining cyclosporine Arpimune concentrations. RESULTS: The abbreviated concentration AUC of Arpimune was similar to that of Neoral, and the 2-hour sampling point (r = 0.813; P < .001) showed the best correlation. Calculated creatinine clearance (mL/min) versus Neoral was 71.36 +/- 13 versus 68.03 +/- 16.6 (P = .61) at 1 month, 70.4 +/- 14.8 versus 64.2 +/- 11.4 (P = .12) at 3 months, and 74.02 +/- 15.8 versus 62.03 +/- 12.1 (P = .002) at 6 months. Two Arpimune versus 4 Neoral patients (P = .67) developed biopsy-proven acute rejection. One septic death occurred in the Arpimune group. Graft survival was 100% in both groups. Hyperlipidemia was the most frequent side effect for both. CONCLUSIONS: The AUC of Arpimune was similar to that of Neoral. Use of the generic cyclosporine Arpimune provided effective immunosuppression in the 6 months after transplantation. Renal allograft function was similar to that of Neoral, with minimal rates of acute rejection and adverse events. PMID- 22310591 TI - Impact of cytochrome P450 3A and ATP-binding cassette subfamily B member 1 polymorphisms on tacrolimus dose-adjusted trough concentrations among Korean renal transplant recipients. AB - BACKGROUND: Tacrolimus is a substrate of cytochrome P450 3A (CYP3A) and P glycoprotein (P-gp), encoded by the CYP3A and ATP-binding cassette subfamily B member 1 (ABCB1) genes, respectively. This study was aimed to investigate the impact of CYP3A and ABCB1 polymorphisms on the tacrolimus pharmacokinetics and clinical outcomes in Korean renal transplant recipients. METHODS: We analyzed data from a cohort of 70 renal transplant recipients receiving tacrolimus. CYP3A4*4, CYP3A4*5, CYP3A4*18, CYP3A5*3, ABCB1 C1236>T, ABCB1 G2677>T/A, and ABCB1 C3435>T polymorphisms were genotyped and correlated to dose-adjusted tacrolimus trough concentration at months 1, 3, 6, and 12 after transplantation. RESULTS: Patients with the CYP3A5*3 alleles showed higher dose-adjusted tacrolimus concentrations for 12 months and higher trough levels until 6 months after transplantation. ABCB1 polymorphisms and haplotypes were not associated with tacrolimus concentrations. In a multivariate analysis, the presence of >=1 CYP3A5*3 allele was a significant independent variable affecting dose-adjusted tacrolimus concentrations. Glomerular filtration rate, acute rejection, opportunistic infection, and graft survival were not affected by CYP3A5 polymorphisms. Calcineurin inhibitor toxicity, which showed higher tendency in patients with CYP3A5*1 alleles, might be associated with higher tacrolimus dose per kilogram. CONCLUSIONS: The CYP3A5 genotype is a major factor in determining the dose requirement of tacrolimus, and genotyping may be of value in individualization of immunosuppressive therapy of renal transplant patients. PMID- 22310592 TI - A 39-month follow-up study to evaluate the safety and efficacy in kidney transplant recipients treated with modified-release tacrolimus (FK506E)-based immunosuppression regimen. AB - BACKGROUND: We initially performed a study to evaluate the safety and efficacy of modified-release tacrolimus (FK506E) in a phase 3, 2-arm, 6-month, randomized, open-label, multicenter trial in Korean living donor de novo kidney transplant recipients. We then performed an extended study to evaluate the long-term safety and efficacy of a FK506E-based regimen up to 45 months posttransplantation in recipients already treated with FK506E. METHODS: Initial study was designed as a randomized, open-label, comparative, multicenter study in de novo living donor kidney transplant recipients. The patients were randomized to an FK506E versus a control (FK506) group (1:1). Recipients who completed a 6-month FK506E treatment study were enrolled in the 39-month follow-up study. Primary end-points were patient and graft survivals at posttransplantation 45 months. Secondary end-point was the incidence of a clinical or biopsy-proven acute rejection episode between 6 and 45 months posttransplantation. RESULTS: In the initial 6-month de novo study 124 enrolled patients were randomized into either the FK506E (n = 62) or the control group (n = 62). The incidence of an acute rejection episode was 19.4% (n = 12) in the FK506E versus 16.1% (n = 10) in the control group (P = .638). There was no mortality or graft failure among the 44 recipients enrolled in this additional 39-month follow-up study. There was 1 patient with biopsy-proven acute cellular rejection episode (2.3%) who underwent steroid pulse therapy with renal function recovery. At the time of study completion 40/44 recipients (90.9%) maintained FK506E treatment. CONCLUSION: This 39-month study following the initial 6-month FK506E study period showed an FK506E-based immunosuppressive regimen in living donor kidney transplantation recipients to be safe and effective. PMID- 22310593 TI - Effect of conversion from twice-daily to once-daily tacrolimus on glucose intolerance in stable kidney transplant recipients. AB - BACKGROUND: Tacrolimus is an established immunosuppressant for the prevention and treatment of allograft rejection in organ transplantation. However, tacrolimus therapy also has several adverse effects. The main aim of this study was to evaluate the effect of conversion from twice-daily tacrolimus (tacrolimus-BID) to once-daily tacrolimus (tacrolimus-OD) on glucose intolerance in stable kidney transplant patients. METHODS: The study comprised 43 kidney transplant recipients with stable renal function. The same 1 mg:1 mg dose conversion was used for all patients. Follow-up, which included clinical evaluation and laboratory testing, was performed at 30, 60, and 120 days after conversion. The parameters for which the baseline and end-point values were determined included homeostasis model assessment of beta-cell function (HOMA-B) scores, hemoglobin A(1c) (HbA(1c)) levels, serum insulin levels, and fasting glucose levels. RESULTS: The tacrolimus trough levels did not differ significantly at 120 days after conversion. There was a significant increase in serum insulin level at 120 days after conversion (baseline, 5.6 +/- 2.7 MUU/mL; end point, 6.6 +/- 3.4 MUU/mL; P < .009). The HOMA B score slightly increased (baseline, 58.7 +/- 33.1; end point, 65.6 +/- 32.8; P = .091) at 120 days after conversion, indicating beta-cell function. Serum creatinine concentration, blood glucose level, and HbA(1c) level did not change significantly during follow-up examinations. Episodes of acute rejection or graft loss did not occur. CONCLUSION: The results of this study suggests that conversion from tacrolimus-BID to tacrolimus-OD may benefit kidney transplant patients with glucose intolerance because of improved insulin secretion. Further studies involving a larger sample population and longer follow-up time are required to verify the results of this study. PMID- 22310594 TI - A switch from conventional twice-daily tacrolimus to once-daily extended-release tacrolimus in stable kidney transplant recipients. AB - BACKGROUND: Extended-release tacrolimus (TAC-ER) was developed to provide a more convenient treatment compliance and improve safety by avoiding toxic peak levels. We prospectively evaluated the safety and effectiveness of a 1:1 dose switch from twice-daily tacrolimus to once-daily TAC-ER in stable kidney transplant recipients and assessed their satisfaction with the regimen. PATIENTS AND METHODS: Tacrolimus was switched to TAC-ER (1:1 dose) in 12 kidney transplant recipients with stable renal function from March 2010 to August 2011. The posttransplantation follow-up period was 7.6 +/- 4.3 years (range 1.5-13.2 years). No patient had diabetes mellitus in this group. We evaluated the tacrolimus trough levels, serum creatinine, potassium, glucose, glycohemoglobin (HbA1c), and urine protein concentrations once a month from 6 months prior to 1 year after switching. A satisfaction survey for TAC-ER treatment was performed 3 months after the switch. The questionnaire included administration compliance questions such as "forget to take less often," "easy to carry," "easy to store," and "general satisfaction." RESULTS: After the switch to TAC-ER, we observed a quick and sustained 25% decrease in TAC trough levels from 4.8 +/- 1.0 to 3.6 +/- 0.8 (P = .0002). No significant differences in serum creatinine, potassium, glucose, HbA1c, or urine protein concentration were observed during the 14.6 +/- 2.6 months' follow-up period. No recipient experienced acute rejection. The satisfaction survey demonstrated that the stable kidney transplant recipients were satisfied with the switch. CONCLUSIONS: A switch from twice-daily tacrolimus to once-daily TAC-ER (1:1 dose) was safe and effective. TAC-ER can improve treatment compliance in stable kidney transplant recipients. PMID- 22310595 TI - Safety and efficacy of conversion from twice-daily tacrolimus (prograf) to once daily prolonged-release tacrolimus (graceptor) in stable kidney transplant recipients. AB - BACKGROUND: Graceptor is a new modified-release once-daily formulation of tacrolimus with an efficacy and safety profile similar to twice-daily tacrolimus (Prograf), as identified by clinical trials, offering a more convenient dosing regimen to improve adherence. The aim of this study was to analyze the safety of a 1:1 dose conversion from twice-daily Prograf to once-daily Graceptor in stable kidney transplant recipients. METHODS: We switched 33 Japanese patients who had undergone kidney transplantation >=1 years before from twice-daily Prograf to once-daily Graceptor. The dose conversion ratio between Prograf and Graceptor was 1:1. We compared the following parameters: minimum tacrolimus concentration (C(min)); concentration dose per weight (CDW); serum creatinine (sCr); blood urea nitrogen (BUN); total cholesterol (TC); high-density lipoprotein cholesterol (HDL C); uric acid (UA); fasting blood sugar (FBS). Time points for measurements were 1 month before study start and 1 and 2 months afterward. RESULTS: The mean age of the subjects in this study was 46.5 +/- 13.1 years. Mean C(min) decreased from 4.55 +/- 1.79 to 3.20 +/- 1.22 ng/dL. The mean CDW also decreased, from 99.8 +/- 69.5 to 75.0 +/- 55.1 mg/dL/kg over the 2 months. There were no significant changes in sCR, BUN, UA, and FBS. Mean TC increased from 187.5 +/- 51.4 to 194.3 +/- 43.4 mg/dL, and mean HDL-C changed from 53.7 +/- 12.0 to 56.1 +/- 11 mg/dL. There were no episodes of rejection or infection. CONCLUSIONS: We conclude that switching from Prograf to Graceptor is safe and has the advantage of improving adherence. It could also have a beneficial effect in controlling glycemic levels and the adverse effects of tacrolimus. In many cases (25%-30%), the minimum concentration of tacrolimus decreased after changing tablets. With Graceptor, the ratio of area under trough level to area under the curve (AUC) is low compared with Prograf, resulting in low C(min) values of 1-2 ng/mL, and the AUC for Graceptor is very similar to that for Prograf. PMID- 22310596 TI - Conversion of stable kidney transplant recipients from a twice-daily prograf to a once-daily tacrolimus formulation: a short-term study on its effects on glucose metabolism. AB - BACKGROUND: The adverse effects of tacrolimus are known to play major roles in posttransplantation diabetes mellitus (PTDM). In the present study, we investigated the effects of conversion from a twice-daily (Tac BID) to a once daily prolonged release of tacrolimus formulation (Tac OD) on glucose metabolism in stable kidney transplant recipients. PATIENTS AND METHODS: In this prospective study, 26 patients converted from Tac BID to the same milligram-milligram daily dose of Tac OD were examined for the effects on renal function, drug trough levels, and glucose metabolism over a 4-week period. RESULTS: Conversion from Tac BID to Tac OD on a 1:1 mg basis resulted in a significant decrease in tacrolimus trough levels, but no significant changes in renal function. At 4 weeks after conversion, a homeostasis model assessment of beta-cell function, and hemoglobin A1c (HbA1c) decreased significantly. CONCLUSIONS: This study demonstrated a significant reduction in tacrolimus trough levels after switching from Tac BID to Tac OD, which increased insulin secretion and decreased HbA1c, suggesting that it may decrease the frequency of PTDM among stable renal transplant recipients. PMID- 22310597 TI - Falsely abnormally elevated blood trough concentration of tacrolimus measured by antibody-conjugated magnetic immunoassay in a renal transplant recipient: a case report. AB - This report presents a falsely abnormally elevated blood trough concentration (C(t)) of tacrolimus measured by antibody-conjugated magnetic immunoassay (ACMIA) methods in a renal transplant recipient. Because the C(t) of tacrolimus was 78.5 ng/mL at day 2 after a 52-year-old man underwent renal transplantation, we stopped the tacrolimus extended-release formulation. However, because the abnormally elevated blood C(t) continued in the range of 41.1-59.1 ng/mL, we then measured the tacrolimus concentration in a stored blood sample before renal transplantation, it was 43 ng/mL. Consequently, the day-7 blood sample was measured with both ACMIA and enzyme-linked immunoassay, showing C(t) values of 42.8 ng/mL and 0.89 ng/mL, respectively. Because the abnormally elevated C(t) was falsely measured by the ACMIA method, we restarted tacrolimus However, the calcineurin inhibitor was subsequently converted to cyclosporine at day 21 after renal transplantation. Although cyclosporine was also measured by ACMIA, there was not an abnormally elevated C(t). Subsequently, the tacrolimus concentration ratio in plasma and whole blood (P/B-tacrolimus concentration ratio) was measured by ACMIA in a posttacrolimus blood sample. The P/B-tacrolimus concentration ratio was 100%. In contrast, the P/B-tacrolimus concentration ratio was <30% in 2 control patients administered tacrolimus. It has been reported recently that there were cases showing falsely slightly elevated C(t) of tacrolimus within the therapeutic range of concentrations. Therefore, we must be careful not to reduce the tacrolimus dose falsely. We consider confirmatory methods for a falsely abnormally elevated C(t) of tacrolimus measured by ACMIA to (1) measure P/B tacrolimus concentration ratio, (2) compare ACMIA with another measurement, and (3) evaluate a blood sample stored before tacrolimus administration. PMID- 22310598 TI - Cyclosporine or tacrolimus: which is the better partner for myfortic or cellcept? AB - BACKGROUND: Mycophenolic acid (MPA) pharmacokinetics using the mycophenolate mofetil (CellCept) formulation are known to differ between patients receiving tacrolimus (FK) or cyclosporine (CyA), but only limited data exist concerning concomitant use of FK or CyA with enteric-coated mycophenolate sodium (EC-MPS; Myfortic). This retrospective study compared the drug interactions with the mycophenolic acid blood levels using different immunosuppressants and their relation to graft survival. PATIENTS AND METHODS: We studied MPA levels in posttransplant sera from 298 renal transplant recipients. RESULTS: Patients receiving immunosuppression with CyA + Myfortic showed 94% at 5- and 10-year graft survivals, which were better than CyA + CellCept (75%, 63%). This combination suppressed posttransplant human leukocyte antigen (HLA) antibody development significantly (P = .03) with higher MPA levels. CONCLUSION: Patients immunosuppressed with CyA + Myfortic showed higher MPA levels and lower posttransplant HLA antibody development as well as the best graft survival. CyA + Myfortic or FK + Cellcept may be better combinations. PMID- 22310599 TI - The efficacy and safety of high-dose mizoribine in ABO-incompatible kidney transplantation using anti-CD20 and anti-CD25 antibody without splenectomy treatment. AB - BACKGROUND: Mizoribine (MZR) has been developed as an immunosuppressive agent in Japan, but it shows less potent immunosuppressive effects at doses up to 3 mg/kg/d. In this study, we investigated whether high-dose MZR (6 mg/kg/d) was effective for ABO-incompatible (ABO-i) living donor kidney transplantation (LKT) using treatment with anti-CD25 and anti-CD20 monoclonal antibodies without splenectomy. METHODS: Since 2007, we encountered 24 cases of ABO-i LKT using anti CD20 and anti-CD25 monoclonal antibody without splenectomy. The pretransplant immunosuppressive regimen consisted of two doses of anti-CD20 antibody, mycophenolate mofetil (MMF), prednisolone, a calcineurin inhibitor (cyclosporine [7 mg/kg] or tacrolimus [0.2 mg/kg] and two doses of anti-CD25 antibody. Antibody removal by plasmapheresis was performed before LKT up to several times according to the antibody titer. The posttransplant regimen consisted of high-dose mizoribine (6 mg/kg/d) instead of MMF (MZR group, n = 12). RESULTS: The 1-year graft survival rates for the MZR and MMF groups were both 100%. The rejection rate in the MZR group (eight %) was not significantly higher than that in the MMF group (seventeen %) Serum creatinine level was not significantly different between the two groups. In the MZR group 6 (50%) patients developed CMV antigenemia-positivity versus 11 (92%) in the MMF group (P < .05). The number of patients who developed CMV disease was 0 in the MZR group and 1 (8%) in the MMF group. The number of patients treated with ganciclovir was 0% and 8%, respectively (not significant). CONCLUSIONS: We obtain good clinical results with high-dose MZR in ABO-i LKT using anti-CD20 and anti-CD25 antibody treatment without splenectomy. PMID- 22310600 TI - A 6-month, open-label, multicenter clinical study in Korean de novo renal transplant patients evaluating the efficacy, safety, and tolerance of myfortic concomitantly used with tacrolimus. AB - Enteric-coated mycophenolate sodium (myfortic, Novartis Pharma AG, Basel, Switzerland) is designed to improve the gastrointestinal tolerability of micophenolic acid. This study was designed to evaluate the efficacy and safety of myfortic in Korean de novo renal transplantation. A total of 65 patients from four transplantation centers received the study drug at least once and were included in the intention-to-treat analysis. This study was an open-label, single arm, multicenter trial with 6-month patient follow-up. Patients received 360 mg (body weight < 50 kg) or 720 mg (body weight > 50 kg) of myfortic per day with tacrolimus and steroids. Induction therapy included basiliximab. The incidence of biopsy-confirmed acute rejection (primary endpoint) within 6 months after transplantation was 7/65 (10.8%). There were 2 (3.1%) graft losses due to severe acute rejection and 1 (1.5%) patient-death due to cardiac arrest. Twenty-two (38.8%) patients experienced gastrointestinal discomfort; however, only 3 (4.5%) cases were associated with an apparent drug reaction. Seventeen (25.4%) patients underwent dose adjustment or myfortic discontinuation during the study period. Patient and graft survival rates at 6 months posttransplantation were 98.1% and 97.0%. Myfortic with tacrolimus-based immunosuppression was efficient and safe after de novo renal transplantation in Korean patients. PMID- 22310601 TI - Excellent results with high-dose mizoribine combined with cyclosporine, corticosteroid, and basiliximab in renal transplant recipients: multicenter study in Japan. AB - We performed a multicenter study in Japan to assess the efficacy and safety of immunosuppressive therapy with high-dose mizoribine (MZR; 6 mg/kg) combined with basiliximab (Bas), cyclosporine (CyA), and a corticosteroid in 90 patients. MZR was adjusted to maintain a target trough level of 1 to 2 MUg/mL. CyA was started at 7 mg/kg to maintain blood levels in the target therapeutic range of 200 ng/mL (trough [C0]), 1200 ng/mL (2-hour post-dose [C2]), and 6000 ng.h/mL (area under the curve(0-9)). Bas (20 mg/body weight) was administered on the day of transplantation and on postoperative day 4. Rejection was diagnosed by episode and protocol biopsies. Cytomegalovirus (CMV) antigenemia (direct immunological staining of leukocytes using peroxidase-labeled monoclonal antibody [C7-HRP]) levels were measured every 2 weeks for 6 months. At 12 months, all patients and grafts were surviving except for one death from infection: the 1-year patient and graft survival rate was 98.9%. The acute rejection rate was 21.1%. The mean serum creatinine level at 1 year was 1.51 +/- 0.61 mg/dL. The incidence of CMV disease was 0% with 28.9%, CMV antigenemia and 5.6%, ganoyclovir treatment. The incidence of BK virus disease was 2.2%. The mean serum uric acid level was 7.15 +/- 1.79 mg/dL at 1 month and 7.06 +/- 1.78 mg/dL at 3 months. We observed that a high dose MZR regimen in combination with CyA, Bas, and corticosteroid was safe and effective to reduce the frequency of CMV and BK virus-related events in renal transplant recipients. PMID- 22310602 TI - Experiences of high-dose mizoribine as antimetabolite immunosuppressants for kidney transplantation. AB - We have used low doses of mizoribine (MZ) or mycophenolate mofetil (MMF) as induction and maintenance immunosuppressants, but since 2009 have employed a high dose of MZ. We reviewed the efficacy and side effects of MZ compared with MMF. It is difficult to compare graft survivals between these periods because of different patient demographics, though the high dose of MZ cohort showed no significant difference from MMF. High doses of MZ serum to prevent acute rejection episodes as the induction and maintenance therapy. MZ controlled with blood concentrations showed less side effects, suggesting that high MZ doses could be safely used for an induction and maintenance antimetabolite. PMID- 22310603 TI - Everolimus with reduced-dose cyclosporine versus full-dose cyclosporine and mycophenolate in de novo renal transplant patients: a 2-year single-center experience. AB - BACKGROUND: Although calcineurin inhibitors (CNIs) has improved short-term graft survival, long-term function remains a challenge. CNIs have been implicated in the development of chronic allograft failure. Low-dose cyclosporine with everolimus may mitigate CNI nephrotoxicity and prolong graft survival. We compared the efficacy and safety of de novo everolimus with low-dose cyclosporine and prednisone versus cyclosporine, mycophenolate, and prednisone among kidney transplant patients up to 24 months after transplantation. METHODS: Kidney transplant patients given low-dose cyclosporine, everolimus, and prednisone were compared with patients given cyclosporine, mycophenolate, and prednisone from December 2006 to December 2008. All had living donors, panel reactive antibody <15%, and follow-up for 2 years after transplantation. Continuous variables using mean and standard deviation, t test and test for proportions were used to determine significant differences between the baseline characteristics of the 2 treatment groups. Generalized linear regression and logistic regression were used to measure the effect of treatment on outcomes. RESULTS: Demographic characteristics were similar in both groups except for age, length of time awaiting kidney transplantation, type of renal replacement therapy, follow-up time, sex distribution, and number of HLA mismatches. These independent variables were used in the generalized linear regression model. There was no significant difference between the everolimus and mycophenolate groups up to 2 years in mean serum creatinine (1.2 mg/dL vs 1.4 mg/dL-, respectively P >= .05), acute rejection (12 months: 20% vs 31%; 24 months: 31% vs 40%; P >= .05), patient survival (98%), and graft survival (100%). Likewise, there were no significant differences in surgical, infectious, metabolic, and gastrointestinal side effects between the 2 groups. CONCLUSIONS: Everolimus with low-dose cyclosporine and prednisone in de novo kidney transplant recipients was similar in efficacy and safety to cyclosporine, mycophenolate, and prednisone. Longer follow-up is needed to see whether everolimus with low-dose cyclosporine will result in improved kidney function. PMID- 22310604 TI - Sirolimus-induced pneumonitis after renal transplantation: a single-center experience. AB - PURPOSE: Sirolimus is a potent immunosuppressive agent used with increasing frequency in kidney transplantation. However, sirolimus can increase the rate of unexplained interstitial pneumonitis. The aim of this study was to evaluate the clinical characteristics of sirolimus-induced pneumonitis and the therapeutic results in renal transplant recipients. PATIENTS AND METHODS: Seventy-two patients received sirolimus, conversion or de novo regimen, at our center between January 2007 and April 2011. Twelve of the 72 patients (16.7%) developed interstitial pneumonitis. The patients were divided into three groups according to the following indications of sirolimus use: de novo, early conversion, and late conversion groups. RESULTS: The mean duration of follow-up was 11.0 +/- 11.5 months. The mean blood level of sirolimus measured by microparticulate enzyme immunoassay was 16.5 +/- 7.4 ng/mL at the time of diagnosis. The mean time from the start of sirolimus to pneumonitis onset was 14.7 +/- 8.0 months. The clinical presentation included fever, cough, dyspnea, general weakness, and periorbital edema. In most cases, radiological imaging tests revealed bilateral lower-lobe involvement. Bronchoalveolar lavage was performed in three patients and two patients showed lymphocytic alveolitis. Sirolimus was discontinued or reduced for the treatment of pneumonitis. All cases of pneumonitis were resolved within 2 to 4 weeks. CONCLUSION: Sirolimus blood level should be monitored tightly and early intervention is important when sirolimus-induced pneumonitis is suspected. PMID- 22310605 TI - Induction therapy by anti-thymocyte globulin (rabbit) versus basiliximab in deceased donor renal transplants and the effect on delayed graft function and outcomes. AB - The use of induction therapy significantly reduces the incidence of acute rejection (AR) episodes posttransplantation and prevents delayed graft function (DGF). In our program, all adult deceased donor kidney transplant (DDKT) recipients receive immunosuppression induction therapy with either basiliximab (anti-CD25 Ab) or rabbit anti-thymocyte globulin (RATG). Our protocol is risk adjusted such that patients who are at a higher risk for DGF or AR received RATG and all other patients receive anti-CD25 Ab. We hypothesized that treating our higher-risk patients with RATG induction at the time of transplantation would lead to a lower rate of DGF and better outcomes. From August 1, 2005 through August 31, 2010, 116 consecutive adult patients received a DDKT in a single academic transplantation center. All DDKT patients received induction with RATG or anti-CD25 Ab. The induction decision was made prior to transplantation based on donor and recipient risk factors for AR and DGF. Transplants that were deemed at higher risk for DGF or AR based on donor factors or recipient factors received RATG. Medical records and patient databases were reviewed retrospectively. The use of RATG in higher-risk recipients for DGF and AR did not significantly reduce the DGF rate. At 6 months the function of the allograft function measured as creatinine clearance or serum creatinine was lower in the RATG group than the patients who received anti-CD25 Ab induction. The choice of induction therapy did not improve outcomes in high-risk patients in this short-term study. PMID- 22310606 TI - Rabbit antithymocyte globulin compared with basiliximab in kidney transplantation: a single-center study. AB - BACKGROUND: Induction therapy is used to reduce the incidence of acute rejection and to prevent or treat delayed graft function. We compared basiliximab with rabbit antithymocyte globulin (ATG) as induction therapies for kidney transplant recipients. METHODS: We retrospectively analyzed the clinical data from 514 patients who received ATG or basiliximab. The patients in the ATG group (n = 152) received ATG (1.5 mg/kg/d) for 5-7 days and those in the basiliximab group (n = 362) were given 2 doses of basiliximab (20 mg) on posttransplantation days 0 and 4. All patients received standard triple immunosuppressive therapy with calcineurin inhibitors, mycophenolate mofetil, and steroids. RESULTS: There were statistically significant differences in the incidences of delayed graft function, 1-year acute rejection rate, death-censored graft survival, and patient survival between the 2 groups, even though the ATG group had more kidney transplants from deceased donors, higher levels of panel reactive antibodies, and more retransplantations. The incidences of cytomegalovirus (CMV) infection and parvovirus infection in the ATG group were higher than those in the basiliximab group. However, there was no statistically significant difference in the incidence of CMV disease between the 2 groups. CONCLUSIONS: ATG is safe and efficacious for use in kidney transplant recipients. Our results suggest that ATG should be considered for induction therapy in high-risk patients, such as those who have a kidney allograft from a deceased donor, high levels of panel reactive antibodies, and are undergoing retransplantation. PMID- 22310607 TI - Comparison between thymoglobulin and ATGAM as an induction agent in adult kidney transplantation: a single-center experience. AB - OBJECTIVE: The best antithymocyte globulin (ATG) preparation for induction suppression in kidney transplant recipients is still not clear. The aim of this study was to identify short- and long-term outcomes in kidney transplant recipients who received thymoglobulin or ATGAM as an induction agent. METHODS: We retrospectively reviewed patients who underwent kidney transplantation from 1996 to 2010. Recipients were classified according to the ATG preparation. RESULTS: One hundred fifty-two patients (64.4%) received thymoglobulin and 84 (35.6%) received ATGAM. The occurrence of delayed graft function in patients receiving thymoglobulin was higher than in patients receiving ATGAM (P = .005), but serum creatinine levels and acute rejection after kidney transplantation were not different between the two groups. The death-censored graft survival curve in thymoglobulin recipients was higher than in ATGAM recipients (P = .027). Bacterial infection was a predisposing factor for graft survival (P = .008). CONCLUSION: The efficacy of thymoglobulin induction is generally better than that of ATGAM induction, and prevention of bacterial infections was just as important as the use of ATG because bacterial infection was an important risk factor for graft failure. PMID- 22310608 TI - Impact of basiliximab on the proportion of regulatory T cells and their subsets early after renal transplantation: a preliminary report. AB - OBJECT: This study aims to investigate the impact of anti-CD25 monoclonal antibody (basiliximab) on peripheral blood regulatory T cells (Treg) and their subsets in recipients early after renal transplantation. METHODS: Ten renal transplant recipients from November 2009 to February 2011 were divided into an induction therapy and a no-induction therapy group, mainly based on their will to accept basiliximab induction. Peripheral blood samples were collected at 2 hours before as well as 1 and 2 weeks after transplantation. Flow cytometry was used to analyze the proportion of regulatory T cells and their subsets. RESULTS: Compared with the no-induction therapy group, the proportions of both CD25(high) T cell and CD25(high) Foxp3(+) double marked T cells were significantly decreased among in the basiliximab induction group remaining at low at 2 weeks. The subsets of activated Treg and cytokine-secreting Treg were also temporarily downregulated at 1 week after transplantation using basiliximab induction. However, the inhibitory transcriptional factor Foxp3 was not significantly affected by the induction therapy. CONCLUSIONS: Anti-CD25 monoclonal antibody downregulated the proportion of regulatory T cell and its activated subsets in peripheral blood in the early stage after renal transplantation while the inhibitory function may still be spared. PMID- 22310609 TI - Early steroid withdrawal in adult kidney transplantation at a single center. AB - BACKGROUND: Beneficial effects of protocols using minimal steroid exposure have been recently reported. The purpose of this study was to evaluate the outcomes of kidney transplantation recipients who received immunosuppression protocols with early steroid withdrawal (ESW) at our center. METHODS: We retrospectively studied 84 kidney transplant recipients who had received ESW immunosuppressive protocols at our center from March 2005 to December 2010. The immunosuppressive regimen was a combination of calcineurin inhibitors (tacrolimus/cyclosporine), methylprednisolone, which was tapered and discontinued within 2 months, mycophenolate mofetil, and basiliximab (postoperative days 0 and 4). We compared the outcomes of our ESW recipients with those of a historical control group (February 2003 to January 2005; n = 18). RESULTS: Clinical acute rejection episodes were observed in 15 (17.9%) and 5 (27.8%) cases in the ESW and control groups, respectively. Cytomegalovirus infection occurred in 12 (14.3%) and 5 (27.8%) cases in the ESW and control groups, respectively. The creatinine levels at 1 year after transplantation were 1.3 +/- 0.4 mg/dL and 1.3 +/- 0.5 mg/dL in the ESW and control groups, respectively. In the ESW group of 84 recipients, actuarial patient survival at 1 year was 94.0%. In the historical group of 18 recipients, the actuarial patient survival at 1 year was 100% (P = .76). In the ESW group the graft survival rate at 1 year was 95.2%. In the historical group, graft survival rate at 1 year was 100% (P = .65). There were no significant differences in the parameters between the groups. CONCLUSIONS: The outcomes from this study were considered to be acceptable; however, the possibility of improving the protocols exists. PMID- 22310610 TI - Effectiveness of rituximab and intravenous immunoglobulin therapy in renal transplant recipients with chronic active antibody-mediated rejection. AB - BACKGROUND: Chronic active antibody-mediated rejection (CAMR) is an important cause of chronic kidney allograft dysfunction, but there has been no effective treatment protocol established for it. METHODS: Six renal transplant recipients who showed progressive deterioration in graft function and CAMR as diagnosed by biopsy were enrolled. We administered a single dose of rituximab (375 mg/m(2)), followed by intravenous immunoglobulin (IVIg, 0.4 g/kg) for 4 days. The efficacy of this protocol was assessed on the basis of the improvement in allograft function, the amount of proteinuria, and the change in donor-specific antibodies (DSAs). We categorized the patients into 2 groups, responders and nonresponders, according to their response to the treatment. RESULTS: All of the patients showed progressive deterioration of graft function before the diagnosis of CAMR. Luminex solid-phase assays showed that 3 patients had DSAs. After the treatment, allograft function improved or stabilized in 3 patients in the responder group, but still showed a deteriorating pattern in the nonresponder group. In the responder group, the amount of proteinuria also decreased after the treatment, but it increased in the nonresponder group. On diagnosis of CAMR, the nonresponders showed a longer posttransplantation period, a higher degree of transplant glomerulopathy, more severely deteriorated allograft function, and higher proteinuria compared with the responders. CONCLUSIONS: The combination of rituximab and IVIg was effective in early-stage CAMR, but the effect was limited in the advanced stage. PMID- 22310611 TI - Trends in the use of immunosuppressive agents by outpatients after renal transplantation at a medical center in southern Taiwan. AB - Kidney transplantation has become an effective treatment for end-stage renal failure. This study analyzed trends in immunosuppressive agent use after renal transplantation at a medical center in southern Taiwan over a 9-year period (2000 2008) seeking to determine whether the trends were consistent with clinical trial outcomes and published guidelines. We identified adult outpatients who had diagnoses of renal transplantation and who had concurrent immunosuppressive drug claims. From 2000-2008, we discovered 39,189 prescriptions related to kidney transplantation. The overall medication consumption showed an increase from 4.9% to 31.9%. Cyclosporine was the main determinant of overall drug costs during these 9 years. The long-term prescribing trend for immunosuppressive use among renal transplantation outpatients showed a clear change during the course of the study. Tacrolimus and sodium mycophenolate/mycophenolate mofetil were used increasingly as combination therapy. However, our survey revealed that management of this transplantation population, especially regarding the use of either calcineurin inhibitor or corticosteroids, was based on potential long-term side effects. PMID- 22310612 TI - Trends in maintenance immunosuppressive drugs used in taiwanese kidney transplant recipients: an analysis of the national health insurance research database. AB - Trends in maintenance immunosuppressive drugs used among Taiwanese kidney transplant recipients have not been reported before. We examined the National Health Insurance Research Database to analyze trends in maintenance immunosuppressive drugs used in Taiwanese kidney transplant recipients for the years 2002-2009. The new case number of kidney transplant recipients ranged from 302 to 673 per year. In 2009, 5276 kidney transplant recipients received immunosuppressive therapy. The 5-year renal graft survival rate of kidney transplant recipients was 93%. In 2009, the most common immunosuppressive therapy among Taiwanese kidney transplant recipients was a triple regimen that included tacrolimus, mycophenolate mofetil, and corticosteroid. There was a significant increase in the use of a tacrolimus-based regimen from 35.1%-58.2%, while the use of cyclosporine decreased from 62.2%-24.8% (P < .05). The percentage of calcineurin inhibitor-free regimen increased from 2.7%-17%. Moreover, the use of Rapamune dramatically increased from 8.2%-22.6% in 2002-2004. However, the percentage of kidney transplant recipients using Rapamune maintained 23 +/- 1.6% in 2004-2009. The use of mycophenolic acid remained stable at about 74.9 +/- 3.2% in 2002-2009. As predicted, the use of Imuran decreased from 6.9%-3.5%. In summary, although calcineurin inhibitors remained the mainstay of immunosuppressive drugs, these findings suggest a general trends toward individualized regimens and the use of calcineurin inhibitor-free and mammalian target of rapamycin inhibitors-based regimens in Taiwanese kidney transplant recipients. PMID- 22310613 TI - Successful transplantation across positive B-cell cross-match in deceased donor renal transplants. AB - A positive T-cell cross-match is a well-established contraindication to deceased donor renal transplantation (DDRT); however, the significance of a positive B cell cross-match (BCXM) remains debatable. Thus, given the high demand and scarce supply for deceased donor (DD) kidneys, only T- and B-cell cytotoxic cross-match negative recipients were considered for DDRT in the past at our institution. Since September 2007, we have started performing DDRT across a historical positive cytotoxic BCXM. When a matched DD kidney became available, patients who were BCXM-positive (BCXM+) on historical sera would undergo repeat cross-match with current sera, using enhanced techniques. BCXM+ and current T-cell immunoglobulin (Ig)G cross-match-negative patients underwent transplantation with enhanced immunosuppression. Donor-specific anti-HLA antibodies (DSA) were tested for only in BCXM+ patients. The present study was designed to review outcomes of historical BCXM+ versus BCXM-negative (BCXM-) DDRT. Between September 2007 and October 2009, 11 BCXM+ and 50 BCXM- DDRT were performed. All patients were followed-up till October 31, 2010. Demographics and sensitization history of both groups were comparable. DSA were present in 6 (54.5%) BCXM+ patients, irrespective of their current cross-match status. All BCXM+ patients received induction immunosuppression with anti-thymocyte globulin, whereas only 60% of BCXM- patients had induction therapy. All BCXM+ patients and the majority of BCXM patients received a calcineurin inhibitor-based maintenance regimen. DSA positive patients received several sessions of plasmapheresis, followed by cytomegalovirus (CMV) hyperimmune globulin after every session. Graft and patient survivals were similar at 12 and 24 months in both groups. Their incidence of BK viremia, CMV antigenemia, and early acute rejection was also similar. The presence of DSA did not increase the risk for acute rejection. Performing DDRT across a positive BCXM with enhanced immunosuppression has enabled highly sensitized patients to receive a transplant with noninferior short-term outcomes compared with low-immunologic risk patients. PMID- 22310614 TI - Successful kidney transplantation after desensitization using plasmapheresis, low dose intravenous immunoglobulin, and rituximab in highly sensitized patients: a single-center experience. AB - BACKGROUND: For many highly allosensitized renal transplant candidates, an acceptable donor is never identified, and the patient remains on dialysis indefinitely. In an attempt to ameliorate this situation, several desensitization protocols have been developed that permit positive-crossmatch kidney transplantation. Here, we report our experiences of living donor kidney transplantation in highly sensitized patients. METHODS: We treated seven highly sensitized patients between March 2003 and September 2009. All patients underwent desensitization using pretransplant plasmapheresis (PP) and low-dose intravenous immunoglobulin (IVIG; 100 mg/kg) with rituximab (six patients) or without rituximab (one patient). Demographics, immunologic characteristics of patients, allograft function, acute rejection (AR) episodes, survival, and adverse events were evaluated. RESULTS: Seven patients with positive-crossmatch tests or high levels of panel-reactive antibody (PRA) were included. Their mean age was 51.4 +/ 3.3 years. The average number of human leukocyte antigen mismatchs was 3.4 +/- 0.5. The mean percent PRA was 41.7% +/- 6.1%. Six patients were crossmatch positive, and one patient was crossmatch-negative but had high PRA levels. The mean follow-up period was 33.2 +/- 5.4 months after transplantation. The all patients showed no AR episodes for follow-up period, and the patient and graft survival rates were 100%. The mean serum creatinine concentration at last follow up was 0.92 +/- 0.11 mg/dL. CONCLUSIONS: Our experiences suggest that the combination of PP and low-dose IVIG with or without rituximab may prove effective as a desensitization regimen for positive-crossmatch and/or highly sensitized living donor renal transplant recipients. Further investigations are needed to evaluate the long-term clinical efficacy and safety of this approach. PMID- 22310615 TI - Excellent outcomes of ABO-incompatible kidney transplantation: a single-center experience. AB - INTRODUCTION: Due to the severe shortage of deceased donors in Japan, ABO incompatible living donor kidney transplantation has been performed since the late 1980s. Excellent long-term outcomes have been achieved; the rates of graft survival among these patients are currently similar to those of recipients of ABO compatible grafts. Our single-center experience describing the immunosuppressive protocols, complications, and grafts survivals is documented in this study. PATIENTS AND METHODS: Among 123 patients with end-stage renal disease who underwent living donor kidney transplantation between January 1999 and December 2010, 25 cases were ABO-incompatible grafts. All of these patients were followed until August 2011. Analyzing these patients, we focused on their immunosuppressive protocols, complications, and graft survivals. RESULTS: Patient and graft survival rates were 100%. One patient experienced antibody-mediated rejection and an intractable acute cellular rejection episode, 1 patient an antibody-mediated rejection, and 6 patients had acute cellular rejection episodes. However, there were no severe complications. CONCLUSION: Although ABO incompatible kidney transplantation is a high-risk procedure, a short-term graft survival rate of 100% may be expected due to recent significant improvements in desensitization and recipient management. PMID- 22310616 TI - Potent immunosuppression for ABO-incompatible renal transplantation may not be a risk factor for malignancy. AB - ABO-incompatible (ABOi) renal transplantation has been increasing, but malignant tumor is a troubling complication of kidney transplantation due to potent immunosuppression. Few previous studies, however, have demonstrated that potent immunosuppression for ABOi living-donor renal transplantation (LDRT) is a risk factor for malignancy. In the present research, data on 252 LDRT patients ftom 2003 to 2008 were retrospectively analyzed to clarify whether ABOi LDRT was associated with malignancy. A potent immunosuppressive regimen for ABOiLDRT consisted of splenectomy, cyclophosphamide, and double-filtration plasmapheresis to minimize the risk of antibody-mediated rejection, in addition to conventional immunosuppresssants including calcineurin inhibitor, prednisolone, and anti-CD25 monoclonal antibody. A total of 11 incidences of malignancy were observed during a median follow-up of 48 months. The incidence rates in ABO-compatible (ABOc; n = 189) and ABOi (n = 63) LDRT groups were 4.2 % (8/189) and 4.8 % (3/63), respectively. Kaplan-Meier survival analysis showed no statistical difference in event-free survival for malignancy between ABOc and ABOiLDRT groups (log-rank P = .73). Multivariable Cox regression analyses identified no associations of malignancy with ABOi LDRT or any immunosuppressant use. In conclusion, our investigation suggested that potent immunosuppression with splenectomy and cyclophosphamide for ABOi LDRT may not be a risk factor for malignancy. PMID- 22310617 TI - Outcomes of pediatric ABO-incompatible kidney transplantations are equivalent to ABO-compatible controls. AB - BACKGROUND: Due to the profound shortage of suitable deceased allografts, much effort has been made to investigate whether successful kidney transplantation (KT) is possible across the ABO blood group barrier even for pediatric recipients. METHODS: We reviewed 52 consecutive ABO incompatible (ABOic) transplantation performed between September 1989 and March 2011. The mean age at transplantation was 10.6 +/- 3.9 years (range, 4.4-19.7), with 35 boys and 17 girls. The donor-to-recipient ABO blood antigen incompatibility was as follows: A1/O (n = 17); B/O (n = 13); A1/B (n = 6); B/A1 (n = 1); A1B/B (n = 9); and A1B/A (n = 6). As a control group, data were collected from 271 pediatric ABO compatible (ABOc) living donor KT in the same period. RESULTS: Overall acute rejection episodes (ARE) among the ABOic group were significantly higher than those of the ABOc group (44% vs 26%; P < .02). However, there was no difference in glomerular filtration rate (GFR) at 1 year after transplantation: 86 +/- 31 mL/min for ABOic vs 99 +/- 37 mL/min for ABOic, respectively. The 1-y, 5-y, and 10-year patient survival rates were 98%, 92%, and 92% in the ABOic group, respectively, and 99%, 98%, and 97% in the ABOc group, respectively (P = not significant [NS]). The overall 1-, 5-, 10-, and 15-year graft survival rates were 94%, 88%, 86%, and 86% in the ABOic group, respectively, and 95%, 92%, 88%, and 78% in the ABOc group, respectively. CONCLUSION: ABOic KT provided long-term allograft and patient survivals equivalent to ABOc live donor transplantations. PMID- 22310618 TI - The correlation of HLA allele frequencies and HLA antibodies in sensitized kidney transplantation candidates. AB - BACKGROUND: The clinical importance of the HLA system is as a transplant antigen. However, correlations between the development and strength of the immune response and HLA genes or specific foreign antigens are not clear. OBJECTIVES: The objectives of this study were to detect HLA-A, -B, and -DRB1 allele frequencies and HLA antibodies in sensitized patients, and to investigate the correlation between the HLA alleles and HLA sensitization. METHODS: This study included 383 sensitized patients and 1000 unsensitized patients awaiting kidney transplantation from 2001-2010. HLA -A, -B, and -DRB1 typing was performed using sequence-specific primer-polymerase chain reactions (SSP-PCR). Arlequin statistical analysis software was used to calculate the HLA allele frequencies among the 2 groups. The anti-HLA-specific antibodies of sensitized patients were identified and analyzed using enzyme-linked immunosorbent assay (ELISA). RESULTS: The numbers of identified HLA -A, -B, and -DRB1 alleles were 20, 43, and 14, respectively. The 5 most frequent HLA alleles in the 2 groups were not different: A-02, 11, 24, 33, 26; B-46, 60, 13, 75, 58; and DR-9, 15, 12, 4, 14. Among the sensitized group, the most frequent HLA-specific antibodies were as follows: A-2, 24, 68, 23, 32; B-27, 56, 57, 7, 60; and DR-7, 4, 9, 13, 17. CONCLUSIONS: There was little correlation between HLA sensitization and HLA alleles of oneself. High frequency alleles and the specificity of high-frequency HLA antibodies were not consistent. PMID- 22310619 TI - Effects of different sensitization events on HLA alloimmunization in solid organ transplantation patients. AB - OBJECTIVE: HLA alloimmunization is caused by various sensitization events, such as transfusion, pregnancy, or organ transplantation. However, the effects of a particular sensitization event on HLA alloimmunization have not been well studied in parallel using an identical test method. We evaluated how different sensitization events affect the panel-reactive antibody (PRA) status in solid organ transplantation candidates. METHODS: PRA identification tests were performed on 674 patients (354 males and 320 females) using Luminex assay kits (LIFECODES, Gen-Probe, Stamford, CT, United States). PRA-positive rates (HLA-A, B, or DR antibodies of median fluorescence intensity [MFI] values of >=1000) and antibody strengths in PRA-positive cases were analyzed according to the different sensitization events and gender. RESULTS: PRA (class I and/or II)-positive rates were significantly higher in patients with transfusion (33.0%; P = .001), pregnancy (71.4%; P < .001), or transplantation events (76.9%; P < .001) than in controls without any identifiable sensitization events (5.6%). Transplantation had the strongest immunization effect, especially for class II HLA antigens. Female compared with male patients (60.3% vs 34.2%; P < .001) and retransplantation compared with first transplantation candidates of kidney transplantation (80.2% vs 41.1%; P < .001) showed a significantly higher PRA positive rate. Retransplantation candidates (MFI 14,164) showed significantly stronger antibody strength than first transplantation candidates (MFI 5456) and those with single sensitization events of transfusion (MFI 4185) or pregnancy (MFI 5548; P < .001 for each). CONCLUSION: Solid organ transplantation appears to have the strongest HLA alloimmunization effect followed by pregnancy and transfusion, especially for class II HLA antigens. PMID- 22310620 TI - Early postoperative spectral Doppler parameters of renal transplants: the effect of donor and recipient factors. AB - BACKGROUND: The objective of this study was to explore the donor and recipient factors related to the spectral Doppler parameters of the transplant kidney in the early posttransplantation period. METHODS: This retrospective study included 76 patients who underwent renal transplantation assessed using Doppler ultrasonography (US) on the first postoperative day. We compared spectral Doppler parameters (peak systolic velocity [PSV] and resistive index [RI]) of the segmental artery of the transplant kidney according to the type of renal transplant, level of serum creatinine (SCr) of donor prior to organ donation, and donor/recipient age. RESULTS: RI was significantly higher in deceased-donor kidney transplantation (DDKT) as compared with living-donor kidney transplantation (LDKT; 0.73 +/- 0.10 vs 0.66 +/- 0.11; P = .007). In the DDKT recipients, multivariate analysis showed donor SCr was the only factor affecting PSV (P = .023), whereas recipient age was the only factor affecting RI (P = .035). In the LDKT recipients, multivariate analysis showed recipient age was the only factor affecting both PSV (P = .009) and RI (P = .018). CONCLUSION: Spectral Doppler parameters in the early posttransplantation period are related to the type of renal transplant, donor renal function, and recipient age. These factors should be taken into consideration when interpreting the results of spectral Doppler US. PMID- 22310621 TI - Clinicopathologic analysis of acute vascular rejection cases after renal transplantation. AB - INTRODUCTION: Histopathologic change of acute vascular rejection (AVR) is characterized by intimal arteritis and transmural arteritis. In this report, we discuss the clinicopathologic analysis of AVR cases after renal transplantation. PATIENTS: AVR was diagnosed in 28 renal transplant recipients followed up in our institute between January 2003 and November 2010. RESULTS: Among 28 cases of AVR, 18 were mild (v1 in Banff 07 classification), 8 were moderate (v2), and 2 were severe (v3). Interstitial inflammation was present in 25 biopsy specimens. Moderate to severe tubulitis (t2-t3) was present in 10 biopsy specimens and transplant glomerulitis in 17; peritubular capillaritis was in 25 of the 28 biopsy specimens. C4d deposition in peritubular capillaries was observed in 11/28 cases. By using assays with plastic beads coated with human leukocyte antigen (HLA) in the 28 cases, we detected circulating anti-HLA alloantibody in 18 patients, among which 11/28 were donor-specific. Acute antibody-mediated rejection was diagnosed in 6 cases. Among AVR cases, 19/28 displayed steroid resistant rejection (SRR) requiring greater anti-rejection therapy (ART), including muromonab CD3 injection, gusperimus injections, plasmapheresis, intravenous immune globulin, and/or rituximab injections. Twenty of 28 patients recovered renal allograft function after ART, and 26/28 grafts are functioning. Among the 2 cases of graft loss, only 1 patient lost his graft due to AVR. CONCLUSIONS: In some cases, AVR might be provoked by anti-donor antibodies. The prognosis of the graft exhibiting AVR was relatively good using available immunosuppression. PMID- 22310622 TI - Cytokine gene expression in peripheral blood mononuclear cells during acute renal allograft rejection. AB - Many studies have explored the participation of cytokines and their genes in renal allograft rejection by using biopsy tissues. To screen for rejection, a biopsy is too invasive to perform without a clinical clue. Therefore, we studied the expression of cytokines that contribute to the early phase of allograft rejection by analyzing mRNA transcripts in sequential blood samples of peripheral blood mononuclear cells (PBMCs) 120 of 6 among patients transplanted before diagnosis of rejection. for comparison with 6 control recipients. The relative expression amount of cytokine genes encoding interleukin (IL) 2, IL-4, IL-10, IL 15, and interferon-gamma were assessed using real-time reverse-transcription polymerase chain reactions. IL-2, IL-4, and IL-15 mRNA expressions in clinically stable prerejection phase of the rejection group were significantly higher than those of the control group. In the prerejection samples, the expression of mRNA encoding IL-10 negatively correlated with the expressions of IL-2, IL-4, and IL 15 mRNAs, which were not different from the positive correlations in the postoperative samples from the control group. The expression patterns of IL-2, IL 4, IL-10, and IL-15 genes in PBMCs after transplantation may help to identify acute rejection episodes before clinical deterioration to monitor the efficacy of immunosuppressive treatment. PMID- 22310623 TI - Abrogation of antibodies improves outcome of renal transplantation. AB - INTRODUCTION: Antibodies are known to cause rejection and therefore are detrimental to graft survival. We describe two protocols of clonal stimulation deletion (CSD) pretransplant followed by grafting with no conventional immunosuppression (IS). METHODS: CSD was employed in 54 patients of mean age, 28.7 years and mean human leukocyte antigen A/B/DR match, 3.25. The two protocols both employed stimulation with donor-specific transfusions and stem cells with deletion using total lymphoid irradiation in group 1 (n = 29) or bortezomib in group 2 (n = 25). Other adjuvants in both protocols were cyclophosphamide, rabbit antithymocyte globulin, and rituximab. Stimulation and deletion were monitored by lymphocyte crossmatches and detection of donor-specific antibodies (DSA). Posttransplant monitoring included serum creatinine (SCr) measurements and antibody detection at regular intervals. Graft biopsy performed in the event of dysfunction was managed by standard guidelines. Rescue IS was initiated upon a rise in SCr or DSA. RESULTS: Mean follow-up in group 1 is 3.28 years and 2.11 years in group 2. There was 100% graft and patient survivals in both cohorts with 23 patients without IS and stable graft function with an SCr of 1.3 mg/dL. All acute rejection episodes, which occurred among 24.1% of group 1 and 20% of group 2, were rescued with therapy evolving as a SCr of 1.6 to 1.9. The majority of rejections were antibody-combined with T-cell-mediated responses. We did not observe untoward effects of the protocol. CONCLUSION: Abrogation of antibodies improved renal transplant outcomes. PMID- 22310624 TI - Association between preoperative allograft function (effective renal plasma flow) and the change in glomerular filtration rate among living-donor kidney transplant recipients. AB - BACKGROUND: Predonation kidney function may be an important factor affecting graft outcome. Increased baseline allograft function may be more effective than strategies to slow the decline in glomerular filtration rate (GFR). However, the role of donor effective renal plasma flow (ERPF) on long-term outcome is less well understood. The purpose of this study was to examine the relationship between preoperative allograft function as measured by ERPF and the decline of allograft function as defined by the annualized change in GFR among living-donor kidney transplant recipients. METHODS: We performed a retrospective analysis of 83 patients who underwent living donor renal transplantation at our institution from March 2001 to October 2010. A time series analysis of autoregressive integrated moving average (ARIMA) model was applied to determine the annualized change in GFR after transplantation. Univariate and stepwise multivariate analyses were performed using linear regression between preoperative ERPF and annualized change in GFR after transplantation. We also investigated the influence on annualized change in GFR of other donor or recipient variables. RESULTS: The ARIMA model revealed that the annualized change in GFR was -1.344 +/ 12.476 mL/min/1.73 m(2) per year. Pearson correlation coefficient for the association between predonation ERPF of the transplanted kidney and the annualized change in GFR was 0.033 (P = .777). CONCLUSIONS: Poor predonation kidney function was not associated with an increased rate of decline of allograft function. Neither donor age nor renal function (preoperative ERPF value) was a valid predictor of change in GFR among living-donor kidney transplant recipients. PMID- 22310625 TI - Kidney transplantation of living unrelated donor-recipient combinations. AB - INTRODUCTION: According to the Japanese renal transplant registry in 2009, there were 1123 living kidney transplantations (LKT), including 35% from spouses (husband/wife). Up to the present in Japan, biologically living unrelated donors (LURD) are most frequently spouses. This study summarized our experience with LURD, especially spousal, kidney transplantation. PATIENTS AND METHODS: We performed 112 cases of LKT between April 2003 and March 2011, including 44 (39%) from spouses and two from other LURD. The other 66 cases received kidneys from living related donors (LRD). We divided the patients into two groups: 44 patients (group 1) received kidneys from spouses (LURD) and 66 (group 2) from LRD. During the induction phase, tacrolimus or cyclosporine, mycophenolate mofetil, and methylprednisolone were prescribed for immunosuppression. Basiliximab was administered on postoperative days 0 and 4. In ABO-incompatible LKT, plasmapheresis was performed to remove anti-AB antibodies prior to LKT; splenectomy or rituximab administration, at the time of or before LKT. RESULTS: Among group 1, one patient died with a functioning graft and one lost her graft. Among group 2, one patient died with a functioning graft and one lost his graft. The incidences of an acute rejection episode were 31.8% and 24.2% in groups 1 and 2, respectively. There were three cases of antibody-mediated rejection in group 1. No patient experienced a lethal infectious complication. CONCLUSIONS: Our results demonstrated that spousal LKT (LURD) was equivalent to LKT from LRD. In response to the shortage of deceased donors, LKT between married couples and from ABO-incompatible donors will spread in Japan. PMID- 22310626 TI - The effect of donor-recipient relationship on long-term outcomes of living related donor renal transplantation. AB - BACKGROUND: Presensitization to human leukocyte antigen (HLA) tends to decrease renal graft survival. During the pregnancy, fetal blood is frequently exposed to the maternal circulation possibly inducing maternal immunization to paternal HLA inherited by the fetus. In this way, pregnancy may occasionally present a hazard to renal graft survival. In this study, we compared retrospectively graft survivals according to living related donor-recipient pairs. MATERIALS AND METHODS: From July 1979 to January 2011, 374 patients underwent living related renal transplantation sharing at least one HLA haplotype with their donor. We compared acute rejection and complication rates as well as long-term graft survival according to the donor-recipient paring: child-to-mother, child-to father, mother-to-child, father-to-child, and one haplotype-matched siblings. All patients received immunosuppressive therapy, consisting of a calcineurin inhibitor, mycophenolate mofetil, or azathioprine and prednisolone. RESULTS: Twenty-one cases (5.6%) were child-to-father paring; 28 (7.5%), child-to-mother; 179 (47.9%), one-haplotype-matched siblings; 46 (12.3%), father-to-child; and 100 (26.7%), mother-to-child paring. Child-to-father pairing displayed the best graft survival; child-to-mother (hazard ratio [HR] = 1.709, P = .662) and one-haplotype matched siblings (HR = 6.589, P = .062) showed no significant difference. Father to-child pares experienced poorer outcomes than child-to-father pairs (HR = 11.579, P = .017) and mother-to-child, the poorest graft survival (HR 17.188, P = .005). CONCLUSION: Pregnancy continues to be a significant source of presensitization in the course of gestation and after parturition. Graft failure can result from an anamnestic reaction subsequent to intrauterine exposure of the mother to HLA of a fetus due to sensitization. PMID- 22310627 TI - Outcome of renal transplantation in Alport's syndrome: a single-center experience. AB - BACKGROUND: Anti-glomerular basement membrane (anti-GBM) nephritis post-renal transplantation (RTx) is known to cause graft loss in Alport's syndrome (AS). We evaluated the results of RTx in AS patients vis a vis patient and graft survivals, incidence of anti-GBM nephritis, and causes of graft failure. MATERIALS AND METHODS: Between 1993 and 2009 we performed 31 RTx on AS patients (28 males and three females) of overall mean age of 22 +/- 7.9 years from six deceased and 27 living donors. Two patients underwent second RTx. RESULTS: Over a follow-up of 1, 3, 5, and 10 years, the mean serum creatinines (mg/dL) were 1.51 +/- 0.52, 1.59 +/- 0.26, 1.61 +/- 0.30, and 1.63 +/- 0.32, respectively. Patient survivals at 1, 5, and 10 years were 89.71%, 81.32% and 81.32% with graft survival for all periods of 81.2%. Twenty-one percent experienced biopsy-proven acute rejection episodes. Graft failures were due to anti-GBM nephritis in 12.2% (n = 4), chronic allograft nephropathy in 3.2% (n = 1), and acute rejection or cyclosporine toxicity 3.2% (n = 1 each). The mean duration to graft loss was 4.9 +/- 2.4 months. CONCLUSION: Graft and patient survivals were acceptable among transplant recipients with AS despite the risk of anti-GBM nephritis. PMID- 22310628 TI - The clinical significance of human leukocyte antigen antibody development in kidney transplantation. AB - BACKGROUND: This retrospective study uses the LAT-M (One Lambda Inc., Calif) screen assay to reexamine the impacts (a), of pretransplant human leukocyte antigen (HLA) antibody on long-term graft survival; (b) posttransplant HLA antibody on long-term graft survival and (c) immunosuppressive regimen on posttransplant HLA antibody development. PATIENTS AND METHODS: Pretransplant sera from 222 renal transplant recipients and posttransplant sera from 216 renal transplant recipients were studied for the impact of HLA antibody on long-term graft survival. RESULTS: Among the patients who did not display pretransplant HLA antibodies, 85% enjoyed 5-year and 59% 10-year graft survival, whereas the patients who tested positive were 83% and 83% (P = .5596). Among the patients who did not show posttransplant HLA antibodies, 99% enjoyed 5-, 91% 10-, and 65% 15 year graft survival, whereas for the 44 patients who tested positive they were 59%, 44%, and 30%, respectively (P < .0001). Patients prescribed cyclosporine + myfortic (odds ratio 0.17, P = .05) or FK + Cellcept (odds ratio 0.36, P = .04) showed the lowest posttransplant HLA antibody development. CONCLUSION: Both regimens improve graft survival. PMID- 22310629 TI - Size does matter-donor-to-recipient body mass index difference may affect renal graft outcome. AB - BACKGROUND: Obesity, in the either kidney donor or the recipient, has been related to worse graft function. The aim of this study was to compare long-term graft outcomes of living-related kidney recipients regarding the donor-to recipient body mass index (BMI) ratio. METHODS: From November 2002 to November 2010, 62 consecutive living-related kidney transplantations were performed at our center. Donor and recipient BMIs were categorized by Taiwan's national standard using dividing values of 18.5, 24, and 27 kg/m(2) to divide subjects into donor to-recipient BMI categories. These with the same BMI category as their donors were defined as the same-BMI group (group 0); recipients with a lower BMI category than their donors were defined as the large-to-small group (group 1); and those with a higher BMI category than their donors were defined as the small to-large group (group 2). Baseline parameters and posttransplantation follow-up data were analyzed according to this grouping. RESULTS: Of the 57 recipients followed regularly at our hospital (mean follow-up 48.9 months), 21 (36.8.1%) were in group 0; 26 (45.6%) in group 1, and 10 (17.6%) in group 2. The baseline parameters were similar among these groups. The overall graft survival rates were 81.0% in group 0, 76.9% in group 1, and 90.0% in group 2. The rejection-free graft survival rates were 81.0%, 65.4%, and 90.0%, respectively. By Kaplan-Meier analysis, group 1 showed worse rejection-free graft survival than group 0 or group 2 (log-rank P = .046). CONCLUSIONS: Living-related recipients of kidneys from donors with a higher BMI showed lower long-term graft survival, which might suggest that petite recipients may need time to compensate adequate blood flow for the relative large graft, thus carrying a higher chance of rejection and worse graft outcomes. PMID- 22310630 TI - Donor-recipient age difference and graft survival in living donor kidney transplantation. AB - BACKGROUND: In paired living kidney exchange donation from an old donor to a young recipient, it may be argued that elderly donors provide an inferior quality kidney. However, the impact of donors older than recipients on transplant outcomes remains unclear. METHODS: We retrospectively reviewed the charts of primary living kidney transplantation patients who were divided into two groups based on the age difference between donor and recipient (recipient age subtracted from donor age, donor-recipient < 20 vs >= 20). The donor-recipient age difference < 20 group comprised 75 and donor-recipient age difference >= 20 group, 25 subjects. Outcome measures included serum creatinine, acute rejection episodes as well as graft and patient survivals at 1 and 5 years after transplantation. RESULTS: The mean donor age difference cohorts of < 20 and >= 20 years showed donor ages of 33 +/- 8 and 54 +/- 8 years, respectively. The mean recipient age in both groups averaged under 40 years. The acute rejection rate within the first year posttransplantation was greater among age difference >= 20 years. The mean serum creatinine values of the donor-recipient age difference < 20 group was lower than the >=20 years group at 1 and 5 years posttransplant. The 1-year difference was associated with an increased creatinine value at 5 years. However, death-censored graft survival of the age difference of the >= 20 years group was not different (hazard ratio [HR] = 0.1, 95% confidence interval [CI] = 0.01-1.37, P = .08). Patient survival of the age difference >= 20 years group showed no difference compared with the age difference < 20 years group (HR = 0.25, 95% CI = 0.01-6.35, P = .4). CONCLUSION: Although the cohort of a donor young recipient age difference >= 20 years showed a greater risk of an acute rejection episode early posttransplantation, it did not affect graft or patient survivals. When considering paired kidney donation, older age donors should not necessarily be limited. PMID- 22310631 TI - Analysis of transplant outcomes after five or six human leukocyte antigen mismatched living donor kidney transplantation. AB - BACKGROUND: Recently, the impact of human leukocyte antigen (HLA) mismatch (MM) on graft outcome has diminished since the introduction of potent immunosuppressive agents, whereas previous reports support the notion that greater numbers of HLA matches are beneficial. This study was undertaken to evaluate outcomes after five or six HLA-mismatched living donor kidney transplantations (LDKT). METHODS: The authors retrospectively reviewed graft function after 2687 LDKTs performed between June 1984 and February 2010. A database of 1364 living related and 1063 living-unrelated donor (LURD) kidney transplantations was used for this study. LURD kidney transplantations were classified into three groups; (1) zero to one HLA MM (n = 158); (2) two to four HLA MM (n = 851); and (3) five to six MM (n = 54). An acute rejection episode was diagnosed based on clinical deterioration of graft function or biopsy findings. Graft survival was calculated using the Kaplan-Meier method. RESULTS: Graft survivals in the zero to one HLA MM, two to four HLA MM, five to six HLA MM, and one-haplo MM LDKT were not significantly different. The rates of acute rejection episodes within 1 year after transplantation were similar irrespective of the HLA MM; (1) zero to one HLA MM (37.3%), (2) two to four HLA MM (35.3%), (3) five to six HLA MM (33.3%; P = .832). CONCLUSIONS: Survival of five or six HLA-mismatched LDKTs was comparable to that of one-haplo MM and relatively well-matched LDKT. The study showed that the presence of five or six HLA MM was not a risk factor for graft survival after LDKT. PMID- 22310632 TI - Does donor kidney to recipient body weight ratio influence long-term outcomes of living-donor kidney transplantation? AB - This study evaluated the effect of the donor kidney to recipient body weight (Kw/Rw) ratio on long-term graft function and survival. We investigated retrospectively whether there was any association between Kw/Rw ratio and long term graft survival and function after a follow-up of >10 years. We studied a consecutive series of 123 adult-to-adult living kidney transplants. According to the Kw/Rw ratio, patients were divided into 3 groups: "low" (Kw/Rw <2.85; n = 29), "medium" (2.85 <= Kw/Rw < 4.04; n = 63), and "high" (>=4.04; n = 31). Among the 3 groups, the mean serum creatinine levels at 1 and 6 months as well as 1 year after transplantation were significantly lower among patients with a high Kw/Rw ratio than in those with a medium or low ratio, but serum creatinine levels at 3 and 5 years did not differ significantly (P = .394 and 0.620, respectively). Graft survival rates at 5 and 10 years after transplantation were significantly lower in the "low" group. We observed a significant association between Kw/Rw ratio and graft survival (P = .018). The Kw/Rw ratio is an important factor for long-term graft survival and early graft function. However, it did not significantly affect subsequent renal function. PMID- 22310633 TI - Clinical characteristics and outcomes of renal transplantation in elderly recipients. AB - BACKGROUND: Elderly renal transplant candidates constitute one the fastest growing populations among end-stage renal disease patients. Since the impacts of advanced recipient age have not yet been fully defined, we evaluated the clinical characteristics and outcomes of elderly renal transplant recipients. METHODS: Among 564 adult renal transplant recipients, at our center between 2000 and 2009, 64 were at least 60 years of age (Elderly group), and 500 were younger than 60 years (Young group) at the time of the procedure. We compared their clinical features and surgical management. RESULTS: There were significant differences in mean donor age (55.6 years vs. 53.2 years, P = .030) and gender mismatch (77.0% vs. 63.4%, P = .035). However, there were no significant differences between the two groups in patient and graft survivals (P = .177 and P = .365, respectively). Malignancy after transplantation was a significant risk factor upon univariate evaluation but only ABO incompatibility upon multivariate analysis of patient and graft survival. The main cause of graft loss among the Elderly group was death with a functioning graft due to heart failure. CONCLUSIONS: Renal transplantation is a feasible, safe option for the elderly and should be actively implemented. However, screening for cancer and heart disease should be mandatory to improve outcomes. PMID- 22310634 TI - Absolute of CD4(+)CD25(+)FOXP3(+) regulatory T-cell count rather than its ratio in peripheral blood is related to long-term survival of renal allografts. AB - CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) may reflect the immune status of kidney transplant (KTx) recipients. Since individual KTx recipients show different lymphocyte counts, we hypothesized that the Treg absolute count rather than its peripheral ratio was more related to long-term survival. We enrolled 42 patients with more than 5-year KTx survival: 32 patients with stable graft function and 10 suffering chronic rejection (CR group). The stable group was divided into four subgroups according to graft survival time: subgroups A (5-6 years); B (6-7 years); C (7-8 years); and D (>8 years). Healthy volunteers were enrolled as controls. We compared the peripheral ratio and absolute count of CD4(+), CD4(+)CD25(+), and CD4(+)CD25(+)Foxp3(+) Tregs. Treg peripheral ratio was not significantly different among the three groups. However, the Treg absolute count was higher among the stable than the CR group (P < .01). Meanwhile, both Treg ratios and absolute counts were altered with renal graft survival. Treg absolute count in subgroups B and C were not only higher than that in subgroup A (P < .05), but also was significantly higher than that in the CR control group or (P < .05). Interestingly, both the Treg ratio and absolute count in subgroup D were lower than those in subgroups B and C (P < .05). Treg quantitation, which alters with graft survival time, may contribute to long-term acceptance of renal allografts. Compared to Treg peripheral ratio, the absolute count may be a superior index to estimate KTx recipient immune status. PMID- 22310635 TI - Changes in quality of life in deceased versus living-donor kidney transplantations. AB - OBJECTIVE: In Japan, >80% of kidney transplantations (KTs) are performed from living donors because of a severe shortage of deceased donors. Moreover, >90% of deceased donors are non-heart-beating donors. In this study, we compared the quality of life (QOL) of the recipients between living- and deceased-donor KT performed in our hospital. METHODS: QOLs of 91 recipients (11 deceased donors and 80 living donors) were analyzed using the Short Form 36 before and 1, 2, and 3 years after KT. Changes in QOLs were compared between deceased-donor KT (group DD) and living-donor KT (group LD). RESULTS: In group DD, physical (PCS) and mental (MCS) component summary scores before transplantation were 43.7 and 48.7, respectively. PCS decreased to 35.3 at 1 year and 34.2 at 2 years, but increased to 52.6 at 3 years. MCS as 43.2 at 1 year, 52.2 at 2 years, and 44.5 at 3 years. In group LD, PCS and MCS before transplantation were 36.9 and 42.6, respectively. PCS increased to 43.3 at 1 year, 47.6 at 2 years, and 51.0 at 3 years, and MCS increased to 47.8 at 1 year, 50.1 at 2 years, and 49.6 at 3 years. CONCLUSIONS: The recipients of living-donor KT showed an improvement of QOL immediately after transplantation. However, in the recipients of deceased-donor KT, physical QOL (PCS) decreased for 2 years after transplantation. The reasons seem to be long waiting period and the use of non-heart-beating donors in deceased-donor KT in Japan. PMID- 22310636 TI - Frequency of T cell expressing Th1 and Th2 associated chemokine receptor in patients with renal allograft dysfunction. AB - Acute rejection of human renal allografts is a frequent, serious posttransplantation complication, occurring in up to 50% of recipients. Leukocyte recruitment is a central feature of acute allograft rejection. Chemokine receptors are expressed on leukocytes in a cell type-specific manner. Recently CCR5+ and CXCR3+ cells have been observed in allograft biopsy specimens of patients undergoing acute cellular rejection (ACR). Herein we investigated the expression of Th1 (CCR5, CXCR3, and CCR2) and Th2 (CCR4, CCR3, and CCR8) associated chemokine receptors on CD4 and CD8 T-cell populations. We sought to correlate chemokine receptor expression in peripheral blood T-cell subsets with the types of graft dysfunction (biopsy-proven rejections). In the peripheral blood CD4+ and CD8+ T-cell populations of patients with graft dysfunction, we observed a high frequency of Th1-associated chemokine receptors CCR5+ and CCR2+ but not CXCR3. PMID- 22310637 TI - Cytomegalovirus infection after prophylactic valganciclovir therapy post-kidney transplantation: case reports. AB - This report describes three patients who developed cytomegalovirus infection 4 months after high-risk donor+/recipient-(D+/R-) kidney transplantation, despite treatment with valgancyclovir (VGCV) for 3 months at low dose (450 mg/d). PMID- 22310638 TI - Metastatic sarcomatoid carcinoma to liver and bone marrow in renal transplant recipient: due to exacerbation of quiescent renal cancer? A case report. AB - Sarcomatoid carcinoma is a rare tumor with rapid growth and a poor prognosis. A 60-year-old man underwent kidney transplantation. Three months after transplantation, multiple tumors were found in the liver and bone, and the patient died several days later. Pathological examination of liver and bone marrow biopsies revealed metastatic sarcomatoid carcinoma. Pretransplantation, the patient's workup was positive only for mild thrombocytopenia and a complicated cyst with peripheral rim calcification (Bosniak IIF) in the right kidney. Retrospectively, we found the abdominal computed tomography film, which had been examined at another hospital 6 years previously. The calcified complicated cyst was a 3-cm enhancing solid mass in the right kidney, suggesting renal cell cancer. It is possible that the cancer developed from the calcified complicated cyst. In this case, immunosuppressants may have altered malignant cell proliferation, invasion, and the form of metastasis. PMID- 22310639 TI - Severe nonfebrile dengue infection in an adolescent after postoperative kidney transplantation: a case report. AB - We herein have reported a case of severe nonfebrile dengue infection complicated with refractory pancytopenia and a large perinephric hematoma with shock in a 16 year-old adolescent during the early postoperative period after kidney transplantation. After the diagnosis of end-stage renal disease she underwent living-related kidney transplantation. Thirteen days after successful transplantation, she exhibited a notable amount of ascites, bilateral pleural effusions, thrombocytopenia, and increased hemoglobin without pre-existent fever. Further investigation revealed positive dengue nonstructural protein 1 antigen (dengue NS1 Ag) and dengue virus serotype 1 by a reverse transcriptase-polymerase chain reaction (RT-PCR) in the patient's serum. She exhibited hemophagocytic syndrome, manifested by refractory pancytopenia and refractory anemia resulting in hypovolemic shock and acute graft failure on day 28 posttransplantation. The anemia was attributed to a large hematoma around the transplanted kidney requiring surgical evacuation of clotted blood. Postoperatively, she gradually recovered with resolution of thrombocytopenia and excellent graft function. Persistent dengue antigenemia and viremia was shown by dengue NS1 Ag and RT-PCR of dengue serotype-1. The viremia was present longer than the dengue antigenemia. Dengue-specific immunoglobulin M (IgM) and IgG by enzyme-linked immunosorbent assay confirmed the primary dengue infection and evidence of a recent donor dengue infection. PMID- 22310640 TI - A case of Ramsay Hunt syndrome in living-kidney transplant recipient. AB - A 36-year-old woman underwent ABO-incompatible living-donor kidney transplantation. Immunosuppression was achieved by quadruple therapy with tacrolimus, basiliximab, mycophenolate mofetil (MMF), and prednisone. Desensitization and removal of anti-ABO antibody was achieved by administration of MMF for 4 weeks before transplantation followed by intravenous administration of rituximab, double-filtered plasmapheresis, and plasma exchange. At 1 month after transplantation, she complained of left ear pain without vesicle rash, tinnitus, and vertigo. Physical examination revealed left facial paralysis and nystagmus. T2 fluid-attenuated inversion recovery magnetic resonance imaging (MRI) visualized swelling of the left facial nerve. Real-time polymerase chain reaction showed the existence of varicella zoster virus DNA in the patient's tears and saliva. The final diagnosis was Ramsay Hunt syndrome without vesicle rash, which is called zoster sine herpete. The patient was treated by intravenous administration of acyclovir (3 mg/kg, 3 times per day) in addition to the reduction of the MMF dose. For facial nerve palsy, prednisolone was prescribed for 3 days and then gradually tapered. These treatments improved the symptoms of tinnitus and vertigo after a month; the facial nerve palsy completely disappeared after 10 months. This case demonstrated MRI to be a useful modality for the early diagnosis of Ramsay Hunt syndrome without vesicle eruption. PMID- 22310641 TI - Vitamin D 25-hydroxylase - Four decades of searching, are we there yet? AB - Bioactivation of vitamin D(3) involves 25-hydroxylation and subsequent 1alpha hydroxylation to produce 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], the active hormone. Six cytochrome P450 enzymes (CYP27A1, CYP2R1, CYP2J2/3, CYP3A4, CYP2D25 and CYP2C11) catalyzing the initial 25-hydroxylation step are reviewed, and their physiological relevance as vitamin D 25-hydroxylases in vivo is discussed. PMID- 22310642 TI - Allosteric regulation of substrate channeling and catalysis in the tryptophan synthase bienzyme complex. AB - The tryptophan synthase alpha2beta2 bi-enzyme complex catalyzes the last two steps in the synthesis of l-tryptophan (l-Trp). The alpha-subunit catalyzes cleavage of 3-indole-d-glycerol 3'-phosphate (IGP) to give indole and d glyceraldehyde 3'-phosphate (G3P). Indole is then transferred (channeled) via an interconnecting 25A-long tunnel, from the alpha-subunit to the beta-subunit where it reacts with l-Ser in a pyridoxal 5'-phosphate-dependent reaction to give l-Trp and a water molecule. The efficient utilization of IGP and l-Ser by tryptophan synthase to synthesize l-Trp utilizes a system of allosteric interactions that (1) function to switch the alpha-site on and off at different stages of the beta subunit catalytic cycle, and (2) prevent the escape of the channeled intermediate, indole, from the confines of the alpha- and beta-catalytic sites and the interconnecting tunnel. This review discusses in detail the chemical origins of the allosteric interactions responsible both for switching the alpha site on and off, and for triggering the conformational changes between open and closed states which prevent the escape of indole from the bienzyme complex. PMID- 22310643 TI - Contribution of p38 MAPK, NF-kappaB and glucocorticoid signaling pathways to ER stress-induced increase in retinal endothelial permeability. AB - Diabetic retinopathy (DR) is characterized by the development of intraretinal microvascular abnormalities. Endoplasmic reticulum (ER) stress is known to play a pathogenic role in vascular impairment in DR. The present study demonstrated that the treatment of human retinal endothelial cells with ER stress inducers such as thapsigargin (Tg) and tunicamycin (Tm) significantly increased the permeability of exogenously added FITC-dextran, accompanied by a decrease of transendothelial electrical resistance (TEER). The expression of claudin-5 among tight junction proteins was significantly decreased by the treatment with Tg or Tm. A p38 MAPK inhibitor, SB203580, and an NF-kappaB inhibitor, dexamethasone, significantly suppressed the Tg-induced down-regulation of claudin-5, decrease of TEER and leakage of added FITC-dextran. The translocation of NF-kappaB p65 subunit to the nucleus was also inhibited by the addition of SB203580 or dexamethasone. The effects of dexamethasone are thought to be due to the transrepression of the above signaling and direct regulation of claudin-5 gene. PMID- 22310644 TI - The novel criteria for predicting pelvic lymph node metastasis in endometrioid adenocarcinoma of endometrium. AB - OBJECTIVE: To identify clinicopathological risk factors for pelvic lymph node metastasis, and to evaluate the clinical validity of these factors in selecting patients who need pelvic lymph node dissection. METHODS: The data of 466 patients who had lymphadenectomy for endometrioid adenocarcinoma of the endometrium between January 2002 and December 2010 were reviewed retrospectively. RESULTS: All patients underwent pelvic lymphadenectomy and 192 (41.2%) patients also underwent paraaortic lymphadenectomy. The median number of pelvic lymph node was 16 (range: 2-46) and of paraaortic lymph node was 5 (range: 2-16). 10.1% (47/466) of all patients had pelvic lymph node involvement and 7.8% (15/192) of the patients had paraaortic lymph node involvement (LNI). Pelvic LNI was significantly more common in the presence of higher grades of tumor, LVSI, deep myometrial invasion, positive peritoneal cytology and cervical involvement. The logistic regression analysis revealed that LVSI, cervical glandular invasion and cervical stromal invasion remained to be the independent risk factors for LNI. When the LVSI and/or cervical involvement were considered as high risk for pelvic lymph node metastasis, NPV and specificity were found to be 96.3% and 68.4%, respectively. LNI was correctly estimated in 323 women (69%), overestimated in 132 women (28%) and underestimated in 11 women (2%). CONCLUSION: LVSI, cervical glandular and stromal involvement were independent risk factors for pelvic LNI. These variables can be assessed pre- or intraoperatively with a high rate of accuracy, the model which uses these variables may be successfully used in the prediction of pelvic lymph node metastasis. PMID- 22310647 TI - A new practical approach towards the synthesis of unsymmetric and symmetric 1,10 phenanthroline derivatives at room temperature. AB - An efficient method towards synthesis of 1,10-phenanthrolines is described. Through Lewis acid-catalyzed annulation reaction between 3-ethoxycyclobutanones and 8-aminoquinolines, a variety of unsymmetric and symmetric 1,10-phenanthroline derivatives were readily prepared with high regioselectivity at room temperature. PMID- 22310648 TI - Accuracy of ECG interpretation in competitive athletes: the impact of using standised ECG criteria. AB - BACKGROUND: Interpretation of ECGs in athletes is complicated by physiological changes related to training. The purpose of this study was to determine the accuracy of ECG interpretation in athletes among different physician specialties, with and without use of a standised ECG criteria tool. METHODS: Physicians were asked to interpret 40 ECGs (28 normal ECGs from college athletes randomised with 12 abnormal ECGs from individuals with known ciovascular pathology) and classify each ECG as (1) 'normal or variant--no further evaluation and testing needed' or (2) 'abnormal--further evaluation and testing needed.' After reading the ECGs, participants received a two-page ECG criteria tool to guide interpretation of the ECGs again. RESULTS: A total of 60 physicians participated: 22 primary care (PC) residents, 16 PC attending physicians, 12 sports medicine (SM) physicians and 10 ciologists. At baseline, the total number of ECGs correctly interpreted was PC residents 73%, PC attendings 73%, SM physicians 78% and ciologists 85%. With use of the ECG criteria tool, all physician groups significantly improved their accuracy (p<0.0001): PC residents 92%, PC attendings 90%, SM physicians 91% and ciologists 96%. With use of the ECG criteria tool, specificity improved from 70% to 91%, sensitivity improved from 89% to 94% and there was no difference comparing ciologists versus all other physicians (p=0.053). CONCLUSIONS: Providing standised criteria to assist ECG interpretation in athletes significantly improves the ability to accurately distinguish normal from abnormal findings across physician specialties, even in physicians with little or no experience. PMID- 22310649 TI - Preventable trauma deaths. AB - OBJECTIVE: To describe methods of estimation and assess preventable deaths and types of errors related to health care. METHODS: A systematic review of articles on preventable trauma deaths published between 2000 and 2009 was conducted. Lilacs, SciELO and Medline databases were searched using the keywords "trauma," "avoidable," "preventable," "interventions" and "complications" and the health sciences descriptors "death," "cause of death," and "hospitals." RESULTS: A total of 29 articles published during the study period were selected. Most were retrospective studies (96.5%). The most common methods used to define avoidability of death were expert panel and injury severity scores. Deaths were categorized as follows: preventable; potentially preventable; and not preventable. The mean preventable death rate was 10.7% (SD 11.5%). The most commonly reported errors were inadequate care management of injured patients and evaluation and treatment errors. CONCLUSIONS: Inconsistent terms were used to categorize deaths and related noncompliances. It is suggested to standardize the terminology for the classification of deaths and types of errors. PMID- 22310650 TI - Care cost for pregnant and parturient women with diabetes and mild hyperglycemia. AB - OBJECTIVE: To compare inpatient and outpatient care costs for pregnant/parturient women with diabetes and mild hyperglycemia. METHODS: A prospective observational quantitative study was conducted in the Perinatal Diabetes Center in the city of Botucatu, Southeastern Brazil, between 2007 and 2008. Direct and indirect costs and disease-specific costs (medications and tests) were estimated. Thirty diet treated pregnant women with diabetes were followed up on an outpatient basis, and 20 who required insulin therapy were hospitalized. RESULTS: The cost of diabetes disease (prenatal and delivery care) was US$ 3,311.84 for inpatients and US$ 1,366.04 for outpatients. CONCLUSIONS: Direct and indirect costs as well as total prenatal care cost were higher for diabetic inpatients while delivery care costs and delivery-postpartum hospitalization were similar. Prenatal and delivery postpartum care costs were higher for these patients compared to those paid by Brazilian National Health System. PMID- 22310651 TI - Time trend of asthma in children and adolescents in Brazil, 1998-2008. AB - OBJECTIVE: To analyze the trends in asthma prevalence in children and adolescents between 1998 and 2008 in Brazil. METHODS: Data on asthma prevalence from the 1998, 2003 and 2008 National Household Sample Surveys were analyzed. The sample was comprised of 141,402, 144,443 and 134,032 individuals in 1998, 2003 and 2008, respectively, and the analysis was adjusted for the sample design. Trends in asthma prevalence were described for sex, Brazilian regions and place of residence of children (zero to nine years of age) and adolescents (ten to 19 years of age). RESULTS: The prevalence of asthma in children was 7.7% in 1998, 8.1% in 2003 and 8.5% in 2008, with an annual increase of 1%. The highest annual increase was observed in the Southeast and North regions (1.4%). Among adolescents, the prevalence of asthma was 4.4% in 1998, 5.0% in 2003 and 5.5% in 2008, with an increase of 2.2% per year. In the Northeast region, the annual increase in the prevalence of asthma was 3.5%. The greatest increases were observed in boys and in residents of rural areas. CONCLUSIONS: Although asthma has decreased in some developing countries, the results found in Brazil point to an increase in this disease in children and adolescents between 1998 and 2008, especially in rural areas. PMID- 22310652 TI - New records of mosquito species (Diptera: Culicidae) from Neuquen and La Rioja provinces, Argentina. AB - The presence of Aedes aegypti is reported beyond its current limit of distribution in Argentina, in the city of Neuquen, Neuquen Province. Ovitraps were placed to collect Ae. aegypti eggs between December 2009 and April 2010. The geographical distribution of Culex eduardoi, Psorophora ciliata and Ps. cingulata is extended with new records from two provinces. PMID- 22310653 TI - Pesticide use and economic impacts on health. AB - OBJECTIVE: To estimate the externalities associated with acute poisoning from pesticides. METHODS: The probabilities of acute poisoning were estimated according to characteristics of rural properties and cities in the state of Parana, Southern Brazil. Information about acute poisoning obtained from the 1998 1999 Harvest Forecast Survey was used. The expected costs with poisoning in these properties were calculated from the sum of medical-hospital expenses and days spent on sick leaves, required for the recovery of intoxicated individuals. A multilevel model was constructed for the analysis. RESULTS: The costs associated with acute poisoning can total up to US$ 149 million for the state of Parana, i.e. for each dollar spent to purchase pesticides in this state, approximately US$ 1.28 may be spent with the external costs of poisoning. This situation could be changed with the implementation of public policies, such as the adoption of an organic agriculture promotion program in the cities where the social cost with acute poisoning could be reduced by approximately US$ 25 million. CONCLUSIONS: Society, especially the populations mainly affected by pesticides, could be benefited by the identification and elimination of the risks of acute intoxication associated with the current model. It is necessary to implement public policies and integrated actions that involve the fields of economics, public health, agronomy, environmental issues, education, and science and technology, among others. PMID- 22310654 TI - Influence of electronic correlations on orbital polarizations in the parent and doped iron pnictides. AB - Orbital polarization and electronic correlation are two essential aspects in understanding the normal-state and superconducting properties of multi-orbital FeAs-based superconductors. In this paper, we present a systematic study on the orbital polarization of iron pnictides from weak to strong Coulomb correlations within the Kotliar-Ruckenstein slave boson approach. The magnetic phase diagram of the two-orbital model for LaFeAsO clearly shows that a striped antiferromagnetic metallic phase with orbital polarization exists over a wide doping range, in addition to the Slater-type insulator, Mott insulator and paramagnetic phases. A reversal of the orbital polarization occurs in the intermediate correlation regime in the absence of the crystal field splitting; however, a small crystal field splitting considerably enhances the orbital polarization, and stabilizes the xz-type orbital order. We argue that the ferro orbital polarization is characteristic of a density wave, and leads to a pseudogap-like behavior in the density of states. PMID- 22310655 TI - Can a functional postural exercise improve performance in the cranio-cervical flexion test?--a preliminary study. AB - Deep cervical flexor (DCF) muscle impairment is common in patients with neck pain. Retraining function is often commenced with a motor relearning approach, requiring the patient to practice and hold a cranio-cervical flexion position in supine lying. Motor relearning requires multiple repetitions which is difficult to achieve if only exercising in supine. This preliminary study investigated the effects of training the DCF with a functional exercise: assumption of an upright lumbo-pelvic and spinal postural position, adding a neck lengthening manoeuvre. The exercise effect was evaluated by changes in sternocleidomastoid (SCM) muscle activity in the cranio-cervical flexion test (CCFT). Twenty subjects with neck pain were randomly assigned to an exercise or control group. The exercise group trained for two weeks. Pre and post-intervention, electromyographic (EMG) signals were recorded from the SCM muscles during the five stages of the CCFT. Results indicated that the exercise improved performance. SCM EMG signal amplitudes decreased across all CCFT stages, albeit significant only at the first and third stages of the test; 22 mmHg (p = 0.043) and 26 mmHg (p = 0.003). No differences were evident in the control group (all p > 0.05). There was no difference between groups for pain and disability measures. This initial study indicates that a postural exercise, convenient to perform during the working day, improves the pattern of SCM muscle activity in the CCFT. Whilst further research is necessary, these observations suggest the worth of such an exercise to augment other training in the rehabilitation of patients with neck pain. PMID- 22310656 TI - Effects of Cr2O3 modification on the performance of SnO2 electrodes in DSSCs. AB - In this paper, we demonstrate that Cr(2)O(3), a visible absorbing insulator, can be used as an efficient blocking layer material for the anode of dye-sensitized solar cells (DSSCs). We prepared SnO(2) electrodes surface-modified with Cr(2)O(3) with various Cr/Sn ratios and studied the effect of the modification on the performance of DSSCs. DSSCs with Cr/Sn ratios 0.02, 0.05, and 0.10 showed increased overall photon-to-electricity conversion efficiency from that of pure SnO(2). Especially, the DSSC with the Cr/Sn ratio 0.02 showed a remarkably large increase by 55%. The electrode materials were analyzed by powder X-ray diffraction, transmission electron microscopy, N(2) adsorption studies, and UV Vis diffuse reflectance spectroscopy. The Cr-containing species appears to be Cr(2)O(3) nanoparticles, spread evenly on the SnO(2) nanoparticles and filling the gap space between SnO(2) particles. The electrochemical properties of the electrodes were characterized by Mott-Schottky plots and electrochemical impedance spectroscopy. As the Cr-content increases, the flat-band potential is negatively shifted. The impedance spectroscopy data show that Cr/Sn = 0.02 and 0.05 samples have lower charge transport resistance at the electrode, which can be explained by the rise of the conduction level due to the charge transfer from the more basic Cr(2)O(3) nanoparticles to SnO(2) nanoparticles. These observations corroborate with the trends of the short-circuit current and the open-circuit voltage of the DSSCs. PMID- 22310657 TI - Why older people refuse to participate in falls prevention trials: a qualitative study. AB - BACKGROUND/OBJECTIVES: Falls are a major public health problem. Older persons are frequently underrepresented in trials, including falls prevention trials. Insight into possible reasons for non-participation could help to improve trial designs and participation rates among this age-group. The aim of this study was to explore reasons why older people refuse to participate in falls prevention trials. SETTING: A qualitative study. PARTICIPANTS: Community-dwelling adults aged >=65 years who attended the Emergency Department due to a fall and refused to participate in a falls prevention trial (IMPROveFALL-study). MEASUREMENTS: A structured interview guide was used, and interview transcripts were subjected to an independent content analysis by two researchers. RESULTS: 15 interviews were conducted. A main reason to refuse trial participation was mobility impairment. In contrast, younger and more "active" and mobile seniors considered themselves "too healthy" to participate. Persons with multiple comorbidities mentioned that they attended a hospital too often, or experienced adequate follow-up by their own physicians already. Transport problems, including distance to the hospital, parking facilities, and travel expenses were another issue. During the interviews it was emphasized by the patients, that they knew the reason for their fall. However, they were not familiar with the positive effects of falls prevention programmes. CONCLUSIONS: Older persons reported multiple reasons to refuse participation in a falls prevention study, such as health-related factors, several practical problems, and personal beliefs about the causes and preventability of falls. Anticipation of those issues might contribute to an improvement in participation rates of older fallers, shorter study duration, and a better generalizability of research findings. PMID- 22310658 TI - Concurrent Koro and Cotard syndromes in a Spanish male patient with a psychotic depression and cerebrovascular disease. AB - Koro and Cotard syndromes are uncommon conditions described in a variety of psychiatric and medical disorders. The authors report the third case of a simultaneous presentation of both syndromes, in a 62-year-old inpatient Spanish male with major depressive disorder with psychotic features, parkinsonism and cognitive impairment. A discussion of the literature and the possible relationship between both syndromes and other neuropsychiatric disorders are presented. PMID- 22310659 TI - Chronic kidney disease and end-stage renal disease predict higher risk of mortality in patients with primary upper gastrointestinal bleeding. AB - BACKGROUND: The outcome of gastrointestinal bleeding in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients is difficult to discern from the literature. Many publications are small, single-center series or are from an era prior to advanced interventional endoscopy, widespread use of proton pump inhibitors or treatment for Helicobacter pylori infections. In this study, we quantify the role of CKD and ESRD as independent predictors of mortality in patients admitted to the hospital with a principal diagnosis of primary upper gastrointestinal bleeding (UGIB). METHODS: We used the Nationwide Inpatient Sample that contains data on approximately 8 million admissions in 1,000 hospitals chosen to approximate a 20% stratified sample of all US facilities. Patients discharged with the principal diagnosis of primary UGIB, CKD or ESRD were identified through the ninth revision of the International Classification of Diseases, clinical modification (ICD-9-CM) codes. The outcome variables included frequency and in-hospital mortality of UGIB in CKD and ESRD patients as compared to non-CKD patients and were analyzed using logistic regression modeling. RESULTS: In 2007, out of a total of 398,213 admissions with a diagnosis of primary UGIB, 35,985 were in CKD, 14,983 in ESRD, and 347,245 in non-renal disease groups. The OR for primary UGIB hospitalization in CKD and ESRD was 1.30 (95% CI 1.17-1.46) and 1.84 (95% CI 1.61-2.09), respectively. The corresponding all-cause mortality OR was 1.47 (95% CI 1.21-1.78) and 3.02 (95% CI 2.23-4.1), respectively. CONCLUSION: Patients with CKD or ESRD admitted with primary UGIB have up to three times higher risk of all-cause in-hospital mortality, warranting heightened vigilance by their clinicians. PMID- 22310660 TI - Rb/E2F1 regulates the innate immune receptor Toll-like receptor 3 in epithelial cells. AB - Tumor suppressor genes regulate the antiviral host defense through molecular mechanisms that are not yet well explored. Here, we show that the tumor suppressor retinoblastoma (Rb) protein positively regulates Toll-like receptor 3 (TLR3) expression, the sensing receptor for viral double-stranded RNA and poly(I . C). TLR3 expression was lower in Rb knockout (Rb(-/-)) mouse embryonic fibroblasts (MEF) and in mammalian epithelial cells transfected with Rb small interfering RNA (siRNA) than in control cells. Consequently, induction of cytokines interleukin-8 and beta interferon after poly(I . C) stimulation was impaired in Rb(-/-) MEF and Rb siRNA-transfected cells compared to controls. TLR3 promoter analysis showed that Rb modulates the transcription factor E2F1, which directly binds to the proximal promoter of TLR3. Exogenous addition of E2F1 decreased TLR3 promoter activity, while Rb dose dependently curbed the effect of E2F1. Interestingly, poly(I . C) increased the Rb expression, and the poly(I . C) induced TLR3 expression was impaired in Rb-depleted cells, suggesting the importance of Rb in TLR3 induction by poly(I . C). Together, these data indicated that E2F1 suppresses TLR3 transcription, but during immune stimulation, Rb is upregulated to block the inhibitory effect of E2F1 on TLR3, highlighting a role of Rb-E2F1 axis in the innate immune response in epithelial cells. PMID- 22310661 TI - Unmodified histone H3K4 and DNA-dependent protein kinase recruit autoimmune regulator to target genes. AB - Autoimmune regulator (AIRE) directs the expression of otherwise tissue-restricted antigens (TRAs) in medullary thymic epithelial cells, allowing their presentation to developing T cells, which leads to central tolerance. We addressed the conundrum of how AIRE is recruited to these otherwise silent genes in cells. Our studies confirmed that interactions between AIRE and the unmodified histone H3K4 (H3K4me0) are important for targeting AIRE to the mouse insulin promoter in chromatin. By replacing its H3K4me0-binding module with one that binds to the methylated H3K4me3, we redirected the mutant AIRE.ING protein to an actively transcribed gene. Nevertheless, the mutant AIRE D297A protein, which could not bind to H3K4me0, still activated the human insulin promoter on an episomal plasmid target. This targeting was due to DNA-dependent protein kinase (DNA-PK). Thus, in cells that lacked the catalytic subunit of DNA-PK (DNA-PKcs), the assembly and activity of AIRE on DNA, whether in chromatin or on episomal plasmids, was abrogated. However, by the heterologous tethering of AIRE to DNA, we could restore its activity on a plasmid target in DNA-PKcs-negative cells. Importantly, mutations in the putative DNA-binding residues in its SAND domain had no effect on the transcriptional effects of AIRE. Thus, AIRE is recruited to TRA genes in chromatin via cooperative interactions with H3K4me0 and DNA-PK. PMID- 22310662 TI - Activation of myeloid cell-specific adhesion class G protein-coupled receptor EMR2 via ligation-induced translocation and interaction of receptor subunits in lipid raft microdomains. AB - The adhesion class G protein-coupled receptors (adhesion-GPCRs) play important roles in diverse biological processes ranging from immunoregulation to tissue polarity, angiogenesis, and brain development. These receptors are uniquely modified by self-catalytic cleavage at a highly conserved GPCR proteolysis site (GPS) dissecting the receptor into an extracellular subunit (alpha) and a seven pass transmembrane subunit (beta) with cellular adhesion and signaling functions, respectively. Using the myeloid cell-restricted EMR2 receptor as a paradigm, we exam the mechanistic relevance of the subunit interaction and demonstrate a critical role for GPS autoproteolysis in mediating receptor signaling and cell activation. Interestingly, two distinct receptor complexes are identified as a result of GPS proteolysis: one consisting of a noncovalent alpha-beta heterodimer and the other comprising two completely independent receptor subunits which distribute differentially in membrane raft microdomains. Finally, we show that receptor ligation induces subunit translocation and colocalization within lipid rafts, leading to receptor signaling and inflammatory cytokine production by macrophages. Our present data resolve earlier conflicting results and provide a new mechanism of receptor signaling, as well as providing a paradigm for signal transduction within the adhesion-GPCR family. PMID- 22310663 TI - Rcf1 and Rcf2, members of the hypoxia-induced gene 1 protein family, are critical components of the mitochondrial cytochrome bc1-cytochrome c oxidase supercomplex. AB - We report that Rcf1 (formerly Aim31), a member of the conserved hypoxia-induced gene 1 (Hig1) protein family, represents a novel component of the yeast cytochrome bc(1)-cytochrome c oxidase (COX) supercomplex. Rcf1 (respiratory supercomplex factor 1) partitions with the COX complex, and evidence that it may act as a bridge to the cytochrome bc(1) complex is presented. Rcf1 interacts with the Cox3 subunit and can do so prior to their assembly into the COX complex. A close proximity of Rcf1 and members of the ADP/ATP carrier (AAC) family was also established. Rcf1 displays overlapping function with another Hig1-related protein, Rcf2 (formerly Aim38), and their joint presence is required for optimal COX enzyme activity and the correct assembly of the cytochrome bc(1)-COX supercomplex. Rcf1 and Rcf2 can independently associate with the cytochrome bc(1) COX supercomplex, indicating that at least two forms of this supercomplex exist within mitochondria. We provide evidence that the association with the cytochrome bc(1)-COX supercomplex and regulation of the COX complex are a conserved feature of Hig1 family members. Based on our findings, we propose a model where the Hig1 proteins regulate the COX enzyme activity through Cox3 and associated Cox12 protein, in a manner that may be influenced by the neighboring AAC proteins. PMID- 22310665 TI - Science in times of crisis. PMID- 22310664 TI - Peroxisome proliferator-activated receptor gamma-dependent regulation of lipolytic nodes and metabolic flexibility. AB - Optimal lipid storage and mobilization are essential for efficient adipose tissue. Nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) regulates adipocyte differentiation and lipid deposition, but its role in lipolysis and dysregulation in obesity is not well defined. This investigation aimed to understand the molecular impact of dysfunctional PPARgamma on the lipolytic axis and to explore whether these defects are also confirmed in common forms of human obesity. For this purpose, we used the P465L PPARgamma mouse as a model of dysfunctional PPARgamma that recapitulates the human ppargamma mutation (P467L). We demonstrated that defective PPARgamma impairs catecholamine-induced lipolysis. This abnormal lipolytic response is exacerbated by a state of positive energy balance in leptin-deficient ob/ob mice. We identified the protein kinase A (PKA) network as a PPARgamma-dependent regulatory node of the lipolytic response. Specifically, defective PPARgamma is associated with decreased basal expression of prkaca (PKAcatalpha) and d-akap1, the lipase genes Pnplaz (ATGL) and Lipe (HSL), and lipid droplet protein genes fsp27 and adrp in vivo and in vitro. Our data indicate that PPARgamma is required for activation of the lipolytic regulatory network, dysregulation of which is an important feature of obesity-induced insulin resistance in humans. PMID- 22310666 TI - Congress vouches for priority review of childhood disease. PMID- 22310667 TI - India mulling stricter laws to curb unethical trials. PMID- 22310668 TI - With bated breath, companies await approval for inhalable drugs. PMID- 22310669 TI - New insight on bariatric surgery difficult to swallow. PMID- 22310670 TI - Spain reeling from budget and staff cuts in biomedicine. PMID- 22310671 TI - Internet data miners strike disease detection gold. PMID- 22310672 TI - Clinicians call for greater transparency in trial recruitment. PMID- 22310673 TI - Fifth time's the charm? PMID- 22310674 TI - Straight talk with...Patrick Soon-Shiong. Interview by Amber Dance. PMID- 22310677 TI - The ultimate endpoint. PMID- 22310678 TI - Action is required to safeguard the future of academic medicine in the UK. PMID- 22310680 TI - Ironing out tau's role in parkinsonism. PMID- 22310681 TI - The road to resistance: EGFR mutation and cetuximab. PMID- 22310682 TI - CD4+ T cells limit the damage in influenza. PMID- 22310683 TI - Building bones by knocking down genes. PMID- 22310684 TI - Cancer-fighting Smurf. PMID- 22310685 TI - An unheard benefit of phosphodiesterase inhibition. PMID- 22310686 TI - A delicate balance: tweaking IL-2 immunotherapy. PMID- 22310687 TI - Puzzling over schizophrenia: schizophrenia as a pathway disease. PMID- 22310688 TI - Puzzling over schizophrenia: schizophrenia, social environment and the brain. PMID- 22310693 TI - Harnessing evolutionary biology to combat infectious disease. PMID- 22310696 TI - Is a liver biopsy necessary in alcoholic hepatitis? PMID- 22310694 TI - Cysteines control the N- and C-linker-dependent gating of KCNH1 potassium channels. AB - KCNH1 (EAG1) is a member of the Kv family of voltage-gated potassium channels. However, KCNH1 channels also show some amino-acid sequence similarity to cyclic nucleotide-regulated channels: they harbor an N-terminal PAS domain, a C-terminal cyclic nucleotide binding homology domain (cNBHD), and N- and C-terminal binding sites for calmodulin. Another notable feature is the channels' high sensitivity toward oxidative modification. Using human KCNH1 expressed in Xenopus oocytes and HEK 293 cells we investigated how oxidative modification alters channel function. Intracellular application of H(2)O(2) or cysteine-specific modifiers potently inhibited KCNH1 channels in two phases. Our systematic cysteine mutagenesis study showed that the rapid and dominant phase was attributed to a right-shift in the voltage dependence of activation, caused by chemical modification of residues C145 and C214. The slow component depended on the C-terminal residues C532 and C562. The cysteine pairs are situated at structural elements linking the transmembrane S1 segment with the PAS domain (N-linker) and the transmembrane channel gate S6 with the cNBH domain (C-linker), respectively. The functional state of KCNH1 channels is determined by the oxidative status of these linkers that provide an additional dimension of channel regulation. PMID- 22310697 TI - A modified Nafion membrane with extremely low methanol permeability via surface coating of sulfonated organic silica. AB - We developed a method to significantly decrease the methanol permeability of a Nafion membrane that does not require sacrificing its proton conductivity and mechanical stability. The Nafion membrane modified by the coating of a thin layer of sulfonated organic silica on the membrane surface exhibits significantly decreased methanol permeability--the permeability is decreased to an undetectable level--while retaining an acceptable ionic conductivity of 0.029 S cm(-1). PMID- 22310699 TI - Factors associated with occupational and academic status in patients with first episode psychosis with a particular focus on neurocognition. AB - PURPOSE: Employment rates for patients with chronic schizophrenia and first episode psychosis (FEP) are low despite a larger variation in reported rates for FEP patients. This could partly be due to various methodologies used. The association between neurocognition and occupational functioning is well known in patients with chronic schizophrenia, while corresponding FEP studies are scarce and results more ambiguous. The current study investigated employment rates in a FEP sample using a threefold division of activity that separated students from employed and unemployed patients. Further, it investigated the relationship between students, employed and unemployed patients and clinical, neurocognitive, global, and social functioning. METHODS: A total of 128 FEP patients with a broad DSM-IV schizophrenia spectrum disorder were assessed with clinical, neurocognitive, and global and social functioning measures. Three groups were defined based on occupational and academic status. RESULTS: Twenty-six percent of the patients were employed, and 23% were students. The students and the employed patients performed better than the unemployed patients on clinical and global and social functioning measures. There were no differences between employed patients and students on any of the investigated measures, although there was a non significant trend for the students to show better working memory capacity compared to the other two groups. CONCLUSIONS: Students and employed patients showed better clinical, global and social functioning compared with unemployed patients. There were no significant differences between the three groups on neurocognitive measures. The results pose an argument for grouping the students with the employed patients if a dichotomous variable is preferred. PMID- 22310700 TI - Epidemiology and comorbidity of severe mental illnesses in the community: findings from a computerized mental health registry in a large Israeli health organization. AB - PURPOSE: Maccabi Healthcare Services, a large health maintenance organization (HMO) operating in Israel, has recently constructed a computerized registry of patients with severe mental illnesses (SMI). In the present study, we aimed to use this registry to investigate the epidemiology of schizophrenia and bipolar affective disorder among adults, and to assess their comorbidity and mortality compared to the general population. METHODS: In this historical cohort study, we investigated the age- and sex-specific prevalence and incidence rates of HMO members diagnosed with schizophrenia or bipolar affective disorder between 2003 and 2009. We compared their medical comorbidity and mortality to the general HMO population. RESULTS: A total of 8,848 and 5,732 patients were diagnosed with bipolar (crude prevalence rate of 5 per 1,000) and schizophrenia (3 per 1,000), respectively. The annual incidence rates were 4.2 and 2.4 per 1,000 for schizophrenia and bipolar disorder, respectively. On average, schizophrenic men were diagnosed 4-5 years earlier than schizophrenic women. Compared to the general population, schizophrenia and bipolar disorder patients had a 12- and 9 year shorter life expectancy, respectively. They were also more likely to be diagnosed with diabetes mellitus (odds ratio of 1.9 and 1.6, respectively). CONCLUSIONS: The current study demonstrates the potential use of automated medical databases to characterize the epidemiology of SMI in the community. The increased comorbidity and mortality among these patients has important implication for health authorities for prevention and delivery of health-care services. PMID- 22310701 TI - PdGa intermetallic hydrogenation catalyst: an NMR and physical property study. AB - The PdGa intermetallic compound is a highly selective and stable heterogeneous hydrogenation catalyst for the semi-hydrogenation of acetylene. We have studied single crystals of PdGa grown by the Czochralski technique. The (69)Ga electric field-gradient (EFG) tensor was determined by means of NMR spectroscopy, giving experimental confirmation of both the recently refined structural model of PdGa and the theoretically predicted Pd-Ga covalent bonding scheme. The hydrogenation experiment has detected no hydrogen uptake in the PdGa, thus preventing in situ hydride formation that leads to a reduction of the catalytic selectivity. We have also determined bulk physical properties (the magnetic susceptibility, the electrical resistivity, the thermoelectric power, the Hall coefficient, the thermal conductivity and the specific heat) of single-crystalline PdGa. The results show that PdGa is a diamagnet with metallic electrical resistivity and moderately high thermal conductivity. The thermoelectric power is negative with complicated temperature dependence, whereas the Hall coefficient is positive and temperature-dependent, indicating complexity of the Fermi surface. Partial fulfillment of the NMR Korringa relation reveals that the charge carriers are weakly correlated. Specific heat measurements show that the density of electronic states (DOS) at the Fermi energy of PdGa is reduced to 15% of the DOS of the elemental Pd metal. PMID- 22310702 TI - Envelope glycoproteins of human immunodeficiency virus type 1 variants issued from mother-infant pairs display a wide spectrum of biological properties. AB - Several studies have shown that the early virus population present in HIV-1 infected infants usually is homogeneous when compared to the highly diversified viral population present at delivery in their mothers. We explored the antigenic and functional properties of pseudotyped viruses expressing gp120 encoded by env clones issued from four mother-infant pairs infected by CRF01_AE viruses. We compared their sensitivity to neutralization and to entry inhibitors, their infectivity levels and the Env processing and incorporation levels. We found that both transmitted viruses present in infants and the variants present in their chronically infected mothers display a wide spectrum of biological properties that could not distinguish between them. In contrast, we found that all the transmitted viruses in the infants were more sensitive to neutralization by PG9 and PG16 than the maternal variants, an observation that may have implications for the development of prophylactic strategies to prevent mother-to-child transmission. PMID- 22310703 TI - Cognitive inhibition and shifting in Asperger's syndrome. PMID- 22310705 TI - Dignity. PMID- 22310704 TI - Ventromedial prefrontal-subcortical systems and the generation of affective meaning. AB - The ventromedial prefrontal cortex (vmPFC) comprises a set of interconnected regions that integrate information from affective sensory and social cues, long term memory, and representations of the 'self'. Alhough the vmPFC is implicated in a variety of seemingly disparate processes, these processes are organized around a common theme. The vmPFC is not necessary for affective responses per se, but is critical when affective responses are shaped by conceptual information about specific outcomes. The vmPFC thus functions as a hub that links concepts with brainstem systems capable of coordinating organism-wide emotional behavior, a process we describe in terms of the generation of affective meaning, and which could explain the common role played by the vmPFC in a range of experimental paradigms. PMID- 22310706 TI - Loved ones obtain various information about the progression of the patient's cancer disease which is important for their understanding and preparation. PMID- 22310708 TI - Risk factors: First statement on sexual activity in patients with cardiovascular disease. PMID- 22310707 TI - Antiplatelet therapy: Can cangrelor bridge the gap to cardiac surgery? PMID- 22310709 TI - Hypertension: Does antihypertensive treatment have long-term benefits? PMID- 22310710 TI - Mitochondria-derived reactive oxygen species negatively regulates immune innate signaling pathways triggered by a DNA virus, but not by an RNA virus. AB - Reactive oxygen species (ROS) are crucial secondary messengers of signaling pathways. Redox-dependent signaling events have been previously described in the innate immune response. However, the mechanism by which ROS modulates anti-viral innate immune signaling is not fully clarified. Here, we report that mitochondria derived ROS differentially regulate the innate response to DNA and RNA viruses (herpes simplex virus (HSV) and Sendai virus (SeV), respectively), with the cytokine response to HSV being negatively regulated by mitochondrial ROS. Importantly, specific activation of Toll-like receptors (TLRs) and DNA receptors (DNARs) but not retinoic acid inducible gene I (RIG-I)-like receptors (RLRs), led to signaling cascades that were inhibited by mitochondrial ROS production. Thus, localized mitochondrial ROS exerts negative modulation of innate immune responses to the DNA virus HSV-2 but not the RNA virus SeV. PMID- 22310711 TI - The nucleotide-binding domain of NLRC5 is critical for nuclear import and transactivation activity. AB - Major histocompatibility complex (MHC) class I and class II are crucial for the function of the human adaptive immune system. A member of the NLR (nucleotide binding domain, leucine-rich repeat) protein family, NLRC5, has recently been identified as a transcriptional regulator of MHC class I and related genes. While a 'master regulator' of MHC class II genes, CIITA, has long been known, NLRC5 specifically associates with and transactivates the proximal promoters of MHC class I genes. In this study, we analyzed the molecular requirements of NLRC5 nuclear import and transactivation activity. We show that NLRC5-mediated MHC class I gene induction requires an intact nuclear localization signal and nuclear distribution of NLRC5. In addition, we find that the nucleotide-binding domain (NBD) of NLRC5 is critical not only for nuclear translocation but also for the transactivation of MHC class I genes. Changing the cellular localization of NLRC5 is likely to immediately impact MHC class I expression as well as MHC class I mediated antigen presentation. NLRC5 may thus provide a promising target for the modulation of MHC class I antigen presentation, especially in the setting of transplant medicine. PMID- 22310712 TI - The combination of lanthanum chloride and the calcimimetic calindol delays the progression of vascular smooth muscle cells calcification. AB - Phosphate (Pi)-binders are commonly used in dialysis patients to control high Pi levels, that associated with vascular calcification (VC). The aim of this study was to investigate the effects of lanthanum chloride (LaCl(3)) on the progression of high Pi-induced VC, in rat vascular smooth muscle cells (VSMCs). Pi-induced Ca deposition was inhibited by LaCl(3), with a maximal effect at 100MUM (59.0+/-2.5% inhibition). Furthermore, we studied the effects on VC of calcium sensing receptor (CaSR) agonists. Gadolinium chloride, neomycin, spermine, and the calcimimetic calindol significantly inhibited Pi-induced VC (55.9+/-2.2%, 37.3+/ 4.7%, 30.2+/-5.7%, and 63.8+/-5.7%, respectively). To investigate the hypothesis that LaCl(3) reduces the progression of VC by interacting with the CaSR, we performed a concentration-response curve of LaCl(3) in presence of a sub effective concentration of calindol (10nM). Interestingly, this curve was shifted to the left (IC(50) 9.6+/-2.6MUM), compared to the curve in the presence of LaCl(3) alone (IC(50) 19.0+/-4.8MUM). In conclusion, we demonstrated that lanthanum chloride effectively reduces the progression of high phosphate-induced vascular calcification. In addition, LaCl(3) cooperates with the calcimimetic calindol in decreasing Ca deposition in this in vitro model. These results suggest the potential role of lanthanum in the treatment of VC induced by high Pi. PMID- 22310713 TI - Expression of Notch receptors and ligands on immature and mature T cells. AB - Notch plays multiple roles in T cell development in the thymus and T cell differentiation in the periphery. In order to systematically examine the role of Notch in T cell biology, we determined the cell surface expression of all Notch receptors and ligands on various populations of T cells by using a panel of specific monoclonal antibodies we recently established. Notch1 and Notch3 were upregulated at double-negative (DN) 2-DN4 stages of immature thymocytes, then downregulated on mature single-positive thymocytes and peripheral T cells, but were rapidly upregulated again upon activation. Notch2 was consistently expressed on T cells while Notch4 was not. Jagged1 and Jagged2 were expressed at double positive stage of immature T cells. Jagged2 was also inducible on mature T cells upon activation. In contrast, no Delta-like (Dll) 1 or Dll4 expression was observed on T cells. These comprehensive profiling of the expression of Notch receptors and ligands would be informative to fully understand the role of individual Notch receptors and ligands in T cell development and differentiation. PMID- 22310714 TI - Muscle contraction increases carnitine uptake via translocation of OCTN2. AB - Since carnitine plays an important role in fat oxidation, influx of carnitine could be crucial for muscle metabolism. OCTN2 (SLC22A5), a sodium-dependent solute carrier, is assumed to transport carnitine into skeletal muscle cells. Acute regulation of OCTN2 activity in rat hindlimb muscles was investigated in response to electrically induced contractile activity. The tissue uptake clearance (CL(uptake)) of l-[(3)H]carnitine during muscle contraction was examined in vivo using integration plot analysis. The CL(uptake) of [(14)C]iodoantipyrine (IAP) was also determined as an index of tissue blood flow. To test the hypothesis that increased carnitine uptake involves the translocation of OCTN2, contraction-induced alteration in the subcellular localization of OCTN2 was examined. The CL(uptake) of l-[(3)H]carnitine in the contracting muscles increased 1.4-1.7-fold as compared to that in the contralateral resting muscles (p<0.05). The CL(uptake) of [(14)C]IAP was much higher than that of l [(3)H]carnitine, but no association between the increase in carnitine uptake and blood flow was obtained. Co-immunostaining of OCTN2 and dystrophin (a muscle plasma membrane marker) showed an increase in OCTN2 signal in the plasma membrane after muscle contraction. Western blotting showed that the level of sarcolemmal OCTN2 was greater in contracting muscles than in resting muscles (p<0.05). The present study showed that muscle contraction facilitated carnitine uptake in skeletal muscles, possibly via the contraction-induced translocation of its specific transporter OCTN2 to the plasma membrane. PMID- 22310715 TI - Methionine sulfoxide reductase B in the endoplasmic reticulum is critical for stress resistance and aging in Drosophila. AB - Methionine sulfoxide reductase B (MsrB) is an enzyme that repairs oxidatively damaged proteins by specifically reducing methionine-R-sulfoxide back to methionine. Three MsrBs, localized in different cellular compartments, are expressed in mammals. However, the physiological roles of each MsrB with regard to its location remain poorly understood. Here, we expressed endoplasmic reticulum (ER)-targeted human MsrB3A (hMsrB3A) in Drosophila and examined its effects on various phenotypes. In two independent transgenic lines, both ubiquitous and neuronal expression of hMsrB3A rendered flies resistant to oxidative stress. Interestingly, these flies also showed significantly enhanced cold and heat tolerance. More strikingly, expression of hMsrB3A in the whole body and nervous system extended the lifespan of fruit flies at 29 degrees C by 43 50% and 12-37%, respectively, suggesting that the targeted expression of MsrB in the ER regulates Drosophila lifespan. A significant increase in lifespan was also observed at 25 degrees C only when hMsrB3A was expressed in neurons. Additionally, hMsrB3A overexpression significantly delayed the age-related decline in locomotor activity and fecundity. Taken together, our data provide evidence that the ER type of MsrB, MsrB3A, plays an important role in protection mechanisms against oxidative, cold and heat stresses and, moreover, in the regulation of fruit fly aging. PMID- 22310716 TI - NR4A nuclear receptors mediate carnitine palmitoyltransferase 1A gene expression by the rexinoid HX600. AB - Retinoid X receptors (RXRs) are members of the nuclear receptor superfamily and can be activated by 9-cis retinoic acid (9CRA). RXRs form homodimers and heterodimers with other nuclear receptors such as the retinoic acid receptor and NR4 subfamily nuclear receptors, Nur77 and NURR1. Potential physiological roles of the Nur77-RXR and NURR1-RXR heterodimers have not been elucidated. In this study, we identified a gene regulated by these heterodimers utilizing HX600, a selective RXR agonist for Nur77-RXR and NURR1-RXR. While 9CRA induced many genes, including RAR-target genes, HX600 effectively induced only carnitine palmitoyltransferase 1A (CPT1A) in human teratocarcinoma NT2/D1 cells, which express RXRalpha, Nur77 and NURR1. HX600 also increased CPT1A expression in human embryonic kidney (HEK) 293 cells and hepatocyte-derived HepG2 cells. Although HX600 induced CPT1A less effectively than 9CRA, overexpression of Nur77 or NURR1 increased the HX600 response to levels similar to 9CRA in NT2/D1 and HEK293 cells. A dominant-negative form of Nur77 or NURR1 repressed the induction of CPT1A by HX600. A protein synthesis inhibitor did not alter HX600-dependent CPT1A induction. Thus, the rexinoid HX600 directly induces expression of CPT1A through a Nur77 or NURR1-mediated mechanism. CPT1A, a gene involved in fatty acid beta oxidation, could be a target of RXR-NR4 receptor heterodimers. PMID- 22310717 TI - O-linked-N-acetylglucosamine modification of mammalian Notch receptors by an atypical O-GlcNAc transferase Eogt1. AB - O-linked-beta-N-acetylglucosamine (O-GlcNAc) modification is a unique cytoplasmic and nuclear protein modification that is common in nearly all eukaryotes, including filamentous fungi, plants, and animals. We had recently reported that epidermal growth factor (EGF) repeats of Notch and Dumpy are O-GlcNAcylated by an atypical O-GlcNAc transferase, EOGT, in Drosophila. However, no study has yet shown whether O-GlcNAcylation of extracellular proteins is limited to insects such as Drosophila or whether it occurs in other organisms, including mammals. Here, we report the characterization of A130022J15Rik, a mouse gene homolog of Drosophila Eogt (Eogt 1). Enzymatic analysis revealed that Eogt1 has a substrate specificity similar to that of Drosophila EOGT, wherein the Thr residue located between the fifth and sixth conserved cysteines of the folded EGF-like domains is modified. This observation is supported by the fact that the expression of Eogt1 in Drosophila rescued the cell-adhesion defect caused by Eogt downregulation. In HEK293T cells, Eogt1 expression promoted modification of Notch1 EGF repeats by O GlcNAc, which was further modified, at least in part, by galactose to generate a novel O-linked-N-acetyllactosamine structure. These results suggest that Eogt1 encodes EGF domain O-GlcNAc transferase and that O-GlcNAcylation reaction in the secretory pathway is a fundamental biochemical process conserved through evolution. PMID- 22310718 TI - NeuroD1 is an upstream regulator of NSCL1. AB - Cell fate determination and differentiation during neurogenesis and myogenesis involve the sequential expression of several basic helix-loop-helix (bHLH) transcription factors. The expression of NeuroD1/2 and the expression of NSCL(Nhlh)1/2 are closely related in many developing peripheral and central neuronal cells, suggesting an epistatic relationship between these two bHLH transcription factor families during neurogenesis. To investigate this relationship, a murine neuroblastoma cell culture system and single/double knock out (KO) mice of NeuroD1 and NeuroD2 were utilized for the gain-of-function and loss-of-function approaches, respectively. Both NeuroD1 and NeuroD2 were able to induce the transcription of NSCL1 in vitro; however, they were not able to activate NSCL2 transcription. The DNA-binding ability of NeuroD1 was essential for NSCL1 induction. To examine the epistatic relationship in vivo, we examined the expression of NSCL1 and NSCL2 in NeuroD1 and NeuroD2 KO mice and NeuroD1/2 compound KO mice by in situ hybridization, RT-PCR and Northern blotting. The expression of NSCL1 was lower in the NeuroD1 KO mice and was not further decreased in the double KO mice. However, the expression of NSCL2 did not change in either the single KO or double KO mice. These results demonstrate that NeuroD1 is an upstream regulator of the NSCL1 gene but not the NSCL2 gene in mice. In addition, NeuroD2 is not involved in this regulatory pathway in vivo. PMID- 22310719 TI - Proteasome inhibition-induced p38 MAPK/ERK signaling regulates autophagy and apoptosis through the dual phosphorylation of glycogen synthase kinase 3beta. AB - Proteasome inhibition is a promising approach for cancer treatment; however, the underlying mechanisms involved have not been fully elucidated. Here, we show that proteasome inhibition-induced p38 mitogen-activated protein kinase regulates autophagy and apoptosis by modulating the phosphorylation status of glycogen synthase kinase 3beta (GSK3beta) and 70kDa ribosomal S6 kinase (p70S6K). The treatment of MDA-MB-231 cells with MG132 induced endoplasmic reticulum stress through the induction of ATF6a, PERK phosphorylation, and CHOP, and apoptosis through the cleavage of Bax and procaspase-3. MG132 caused the phosphorylation of GSK3beta at Ser(9) and, to a lesser extent, Thr(390), the dephosphorylation of p70S6K at Thr(389), and the phosphorylation of p70S6K at Thr(421) and Ser(424). The specific p38 inhibitor SB203080 reduced the p-GSK3beta(Ser9) and autophagy through the phosphorylation of p70S6K(Thr389); however, it augmented the levels of p-ERK, p-GSK3beta(Thr390), and p-70S6K(Thr421/Ser424) induced by MG132, and increased apoptotic cell death. The GSK inhibitor SB216763, but not lithium, inhibited the MG132-induced phosphorylation of p38, and the downstream signaling pathway was consistent with that in SB203580-treated cells. Taken together, our data show that proteasome inhibition regulates p38/GSK(Ser9)/p70S6K(Thr380) and ERK/GSK3beta(Thr390)/p70S6K(Thr421/Ser424) kinase signaling, which is involved in cell survival and cell death. PMID- 22310720 TI - New method to differentiate human peripheral blood monocytes into insulin producing cells: Human hematosphere culture. AB - Strategy to differentiate stem cells into insulin producing cells (IPCs) in vitro has been a promising one to get cell source of beta-cell replacement therapy for diabetes. It has been suggested that islets and neurons share features and nestin positive cells could differentiate into IPCs. We have recently developed a three dimensional culture system using human peripheral blood cells named as blood-born hematosphere (BBHS). Here we showed that most of BBHS were composed of nestin positive cells. Under the four-stage differentiation protocol for IPCs, we plated nestin-positive BBHS onto fibronectin-coated dish. These cells form islet-like clusters and most of them expressed insulin. Pancreatic specific genes were turned on, such as transcription factors (Pdx-1, Ngn3 and Nkx6.1), genes related to endocrine function (Glut-2 and PC2) or beta cell function (Kir6.2, SUR1). Furthermore islet differentiation was confirmed by dithizone (DTZ) staining to detect zinc ion which binds insulin protein within the cells. Finally, IPCs derived from BBHS showed capability to secrete insulin in response to glucose stimulation. Taken together, our novel protocol successfully induced islet-like human insulin producing cells out of BBHS. This strategy of ex vivo expansion of IPCs using BBHS provides an autologous therapeutic cell source for the treatment of diabetes. PMID- 22310721 TI - Comparative autoantibody profiling before and after appearance of malignance: identification of anti-cathepsin D autoantibody as a promising diagnostic marker for lung cancer. AB - Cancer patients frequently develop autoantibodies. To test the hypothesis that the appearance of autoantibodies precedes the clinical diagnosis of cancer, we applied an immunoproteomic approach to compare autoantibody profiles before and after appearance of malignances. Proteins from A549 cells, a lung adenocarcinoma cell line, were separated by two dimensional electrophoresis and then immunoblotted with serum samples from 8 individuals who were eventually diagnosed with lung cancer. Compared with autoantibody profiles from 3 years prior to the appearance of malignances, 21 immunoreactive spots newly appeared or presented with stronger staining intensity when clinical diagnoses were made. Among them, 10 matched spots on 2-DE gels were identified by mass spectrometry analysis as 5 proteins. With immunoprecipitation analysis, the antigenicity of protein cathepsin D was confirmed, and notably, in lung cancer sera, the occurrences of autoantibodies against the specific forms of cathepsin D differed significantly from the control groups (p<0.05). Our findings suggest that harnessing immunity may have utility for early cancer marker discovery, and that comparing autoantibodies to specific forms of cathepsin D may be a promising early marker of lung cancer. PMID- 22310722 TI - Protein phosphatase 2A effectively modulates basal L-type Ca(2+) current by dephosphorylating Ca(v)1.2 at serine 1866 in mouse cardiac myocytes. AB - Calcium (Ca(2+)) influx through Ca(v)1.2 L-type Ca(2+) channels is an important event for cardiac excitation-contraction (E-C) coupling. The functional regulation of Ca(v)1.2 is controlled by multiple kinases and phosphatases. It has been well documented that phosphorylation of Ca(v)1.2 by PKA or other kinases is sufficient for the upregulation of channel activity. However, little is known about the role of protein phosphatases in counterbalancing the phosphorylation of Ca(v)1.2, especially the degree to which protein phosphatase 2A (PP2A)-mediated dephosphorylation is involved in the regulation of Ca(v)1.2 in the mouse heart. Here, we report a physical interaction between PP2A and the C-terminus of Ca(v)1.2 in mouse heart extracts as revealed by coimmunoprecipitation. This interaction was further confirmed by the observation that PP2A and Ca(v)1.2 are colocalized in isolated mouse cardiomyocytes. Specifically, PP2A was bound at serine 1866 in the C-terminus of Ca(v)1.2, and PP2A-induced Ca(v)1.2 dephosphorylation at serine 1866 was observed in mouse cardiomyocytes. Importantly, the density of L-type calcium current increased in line with the increase in the phosphorylation at serine 1866 of Ca(v)1.2 in cardiac-specific PP2A Calpha knockout mice. These phenomena were reproduced by treatment with okadaic acid, a PP2A inhibitor, in H9c2 cells. In summary, our data reveal the functional role of PP2A in cardiac Ca(v)1.2 regulation. PMID- 22310723 TI - A phase II study of capecitabine plus oxaliplatin as first-line chemotherapy in elderly patients with advanced gastric cancer. AB - OBJECTIVE: This study aimed at assessing the efficacy and safety of oxaliplatin plus oral capecitabine (XELOX regimen) as first-line chemotherapy in elderly patients with advanced gastric cancer (AGC). PATIENTS AND METHODS: Forty-six eligible patients aged >=70 years with previously untreated AGC received oxaliplatin 130 mg/m(2) intravenously over a 2-hour period on day 1 plus oral capecitabine 850 mg/m(2) twice daily on days 1-14, every 3 weeks. RESULTS: All patients were evaluable for toxicity and 45 patients for efficacy. A median of 6 cycles (range 1-8) was administered. The overall response rate was 48.9% (95% CI 34-64) with 1 complete response, 21 partial responses, 15 stable diseases and 8 progressions. Median time to progression was 6.0 months (95% CI 3.9-8.1), and the median overall survival was 10.0 months (95% CI 8.6-11.4). Toxicity was fairly mild. Grade 3 toxicities included neutropenia (6.5%), thrombocytopenia (2.2%), nausea (2.2%), vomiting (4.3%), diarrhea (4.3%) as well as peripheral neuropathy (2.2%); grade 4 toxicities occurred in none of the patients. CONCLUSION: The XELOX regimen with capecitabine at a lower dose of 850 mg/m(2) is active, fairly tolerable and conveniently delivered as first-line chemotherapy for elderly AGC patients. PMID- 22310724 TI - Synthesis and in vitro cytotoxicity of cis,cis,trans diamminedichloridodisuccinatoplatinum(IV)-peptide bioconjugates. AB - The synthesis and characterization of four Pt(IV)-peptide conjugates, containing one or two peptides in the axial position, designed for the purpose of targeted drug delivery to tumor cells, are described. The precursor cis,cis,trans diamminedichloridodisuccinatoplatinum(IV) was coupled in the last step of standard solid-phase peptide synthesis (SSPS) with an analogue of neurotensin (pseudo-neurotensin = Lys-Lys-Pro-Tyr-Ile-Leu) and with octreotate (D-Phe-Cys-Phe D-Trp-Lys-Thr-Cys-Thr-OH), an analogue of somatostatin, respectively. For all peptides, the SSPS reactions afforded both mono- and diconjugated Pt-peptide species, which were separated and purified by RP-HPLC. The two couples of conjugates, together with the precursor, were tested as cytotoxic agents towards different cancer cell lines. In general all conjugates are good inhibitors of cellular proliferation when compared to a nontargeting platinum(IV) parent compound, so that its relatively low cytotoxicity is greatly improved by addition of the peptides. PMID- 22310725 TI - Drug development: longer-lived proteins. AB - Protein therapeutics represent a powerful class of clinically approved drugs for the prevention and treatment of various diseases. Once administered, the biological fate of protein therapeutics is governed by the body's various complex biochemical and biophysical clearance mechanisms, several of which may decrease the drug's circulation time and efficiency. In this tutorial review, we introduce the concepts of physiological protein clearance from the body, and describe several chemical modification and protein engineering approaches used to improve the life span of administered protein therapeutics. PMID- 22310726 TI - Detection of melanoma using antibody-conjugated quantum dots in a coculture model for high-throughput screening system. AB - We proposed an effective strategy for evaluating the targeting specificity of an antibody-conjugated quantum dot (QD) nanoprobe in a coculture system mimicking an in vivo-like tumor microenvironment in which cancer cells grow with normal cells. Analysis of the images was performed with automated confocal microscopy. We have employed a melanoma-melanocyte coculture model to assess the specific binding of QDs conjugated with melanoma antibodies. Conjugation of antibodies to the QD significantly improved the melanoma specificity, while unconjugated antibody alone suffered from non-specific binding to melanocytes. Concentration-dependent binding and competitive inhibition studies with QD-antibody conjugates reproducibly proved the specificity to melanoma cells against melanocytes. The specificity and targeting efficiency of nanoprobes evaluated in a simple coculture model may provide a reasonable assessment for the in vitro diagnosis of early stage melanoma development before in vivo studies. Further, a rapid and sensitive cancer cell detection system demonstrated herein may allow for the development of high-throughput screening platforms for early cancer diagnosis and anti-cancer therapeutics. PMID- 22310727 TI - Backboards are important when chest compressions are provided on a soft mattress. AB - AIM: Determine the impact of backboard placement, torso weight and bed compression on chest compression (CC) depth feedback in simulated cardiac arrest patients. METHODS: Epochs of 50 high quality CCs with real-time feedback of sternum-to-spine compression depth were provided by a blinded BLS/ACLS/PALS certified provider on manikins of two torso weights (25 vs. 50 kg), using three bed surfaces (stretcher, Stryker hospital bed with Impression mattress, soft Total Care ICU bed), with/without a backboard (BB). Two BB sizes were tested (small: 60 cm * 50 cm; large: 89 cm * 50 cm) in vertical vs. horizontal orientation. Mattress displacement was measured using an accelerometer placed internally on the spine plate of the manikin. Mattress displacement of >= 5 mm was prospectively defined as the minimal clinically important difference. RESULTS: During CPR (CC depth: 51.8 +/- 2.8mm), BB use significantly reduced mattress displacement only for soft ICU beds. Mattress displacement was reduced (vs. no BB) for 25 kg torso weight: small BB12.3mm (95%CI 11.9-12.6), horizontally oriented large BB 11.2mm (95%CI 10.8-11.7), and vertically oriented large BB 12.2mm (95%CI 11.8-12.6), and for 50 kg torso weight: small BB 7.4mm (95%CI 7.1-7.8), horizontally oriented large BB 7.9 mm (95%CI 7.6-8.3), and vertically oriented large BB 6.2mm (95%CI 5.8-6.5; all p<0.001). BB size and orientation did not significantly affect mattress displacement. Lighter torso weight was associated with larger displacement in soft ICU beds without BB (difference: 6.9 mm, p<0.001). CONCLUSION: BB is important for CPR when performed on soft surfaces, such as ICU beds, especially when torso weight is light. BB may not be needed on stretchers, relatively firm hospital beds, or for patients with heavy torso weights. PMID- 22310728 TI - Assessment of CPR interruptions from transthoracic impedance during use of the LUCASTM mechanical chest compression system. AB - BACKGROUND: Quality of cardiopulmonary resuscitation (CPR) is a key determinant of outcome following out-of-hospital cardiac arrest (OHCA). Recent evidence shows manual chest compressions are typically too shallow, interruptions are frequent and prolonged, and incomplete release between compressions is common. Mechanical chest compression systems have been developed as adjuncts for CPR but interruption of CPR during their use is not well documented. AIM: Analyze interruptions of CPR during application and use of the LUCASTM chest compression system. METHODS: 54 LUCAS 1 devices operated on compressed air, deployed in 3 major US emergency medical services systems, were used to treat patients with OHCA. Electrocardiogram and transthoracic impedance data from defibrillator/monitors were analyzed to evaluate timing of CPR. Separately, providers estimated their CPR interruption time during application of LUCAS, for comparison to measured application time. RESULTS: In the 32 cases analyzed, compressions were paused a median of 32.5s (IQR 25-61) to apply LUCAS. Providers' estimates correlated poorly with measured pause length; pauses were often more than twice as long as estimated. The average device compression rate was 104/min (SD 4) and the average compression fraction (percent of time compressions were occurring) during mechanical CPR was 0.88 (SD 0.09). CONCLUSIONS: Interruptions in chest compressions to apply LUCAS can be <20s but are often much longer, and users do not perceive pause time accurately. Therefore, we recommend better training on application technique, and implementation of systems using impedance data to give users objective feedback on their mechanical chest compression device use. PMID- 22310729 TI - Aerobic oxidation of alcohols in the liquid phase with nanoporous gold catalysts. AB - Aerobic oxidation of alcohols in the liquid phase proceeded smoothly in the presence of nanoporous gold catalyst. The catalyst is reusable multiple times without leaching and loss of the catalytic activity. The reaction was applied successfully to a flow system. Adsorptions of O(2) and 1-phenylethanol into the AuNPore were confirmed by TDS analysis. PMID- 22310730 TI - Understanding Cr segregation at the He bubble surface in Fe. AB - Although Cr segregation at the free Fe surface is weak, noticeable segregation of Cr at the He bubble surface in Fe has recently been observed. To understand the driving force for Cr segregation, we have carried out first-principles density functional theory calculations on the energetics of solute Cr atoms at the He bubble surface, which was modeled by a Fe/He interface. We find that both the compressive stress produced by the He bubble and the direct interfacial interaction promote Cr segregation from inside the bulk to the bubble surface, along with reduced spin polarization. Electronic structure analyses show that at the Fe/He interface, Cr is more compressible than Fe due to having more empty e(g) orbitals and, accordingly, the Fe surface gets energetically more favorable for Cr than in the bulk. On the other hand, the segregation of Cr increases the charge density at the bubble surface, and thus hinders assimilation of further He atoms. PMID- 22310731 TI - The origin of the concept of psychosis: Canstatt 1841. PMID- 22310732 TI - Circulating CD4+ CD25brightFOXP3+ regulatory T-cells are significantly reduced in bullous pemphigoid patients. AB - Bullous pemphigoid (BP) is the most frequent autoimmune bullous skin disease, characterised by auto-antibodies against the hemidesmosome complex. Recently, regulatory T cells (Tregs) have been implicated in the development of several autoimmune diseases; few data are available in BP, failing to demonstrate a role of this subset in disease pathogenesis. The aim of this study was to investigate the expression and phenotypes of different Tregs (CD4+ CD25brightFOXP3+ and CD8+ CD28- cells) in BP to clarify whether the depletion of this subset constitutes one mechanism of tolerance loss. The CD4+ CD25brightFOXP3 and CD8+ CD28- circulating subsets were determined by flow-cytometry in 26 untreated BP patients and compared with a group of age- and sex-matched healthy controls (HC, n = 30). Absolute and percentage values of the CD4+ CD25brightFOXP3+ cells were significantly reduced in BP compared with HC (median CD25brightFOXP3+ expression within CD4+ cells: 1.8 vs. 3.5%, p = 0.002); conversely, BP patients were characterised by a significant expansion of the CD25brightFOXP3- "activated" T cell subset. CCR4 and CD62L were expressed on the majority of CD4+ CD25brightFOXP3+ cells (75.2 and 82.3%, respectively). No differences in the CD8+ CD28- subset were found between BP and HC. This is the first report showing a significant reduction of circulating CD4+ CD25brightFOXP3+ Treg frequency in BP patients. PMID- 22310733 TI - Nrf2-dependent and Nrf2-independent induction of phase 2 detoxifying and antioxidant enzymes during keratinocyte differentiation. AB - As antioxidant enzymes can be actively modulated during keratinocyte (KC) differentiation, this study was aimed to evaluate the modulation of a group of phase 2 detoxifying and antioxidant enzymes (phase 2 enzymes) during KC differentiation. In postconfluence-induced differentiation model of KC, heme oxygenase-1 (HO-1), NADP(H):quinone oxidoreductase-1 (NQO-1), and glutathione S transferase pi (GSTpi) were up-regulated at a transcriptional level. In Western blot analysis, the phase 2 enzymes were up-regulated by H(2)O(2), but down regulated by N-acetyl cysteine, indicating the active role of reactive oxygen species for their expression during KC differentiation. When a redox-sensitive NF E2 related factor-2 (Nrf2), a key transcriptional factor for phase 2 enzymes, was knocked down by small interfering RNA transfection in differentiated KCs, only NQO-1 was down-regulated in both mRNA and protein levels. In human skin, expression levels of the phase 2 enzymes were up-regulated in the differentiated KC in the normal epidermis and keratotic foci in squamous cell carcinoma, further supporting the differentiation-dependent expression of phase 2 enzymes in vivo. This study demonstrates that a group of phase 2 enzymes are modulated during KC differentiation via either Nrf2-dependent (NQO-1) or Nrf2-independent (HO-1 and GSTpi) ways. PMID- 22310734 TI - Magnesium sulfate protects fetal skin from intrauterine ischemia reperfusion injury. AB - Intrauterine ischemia-reperfusion (I/R) injury in fetus occurs with multifactorial pathogenesis and results with multiorgan injury including skin. Magnesium has widespread use in obstetric practice. Inn addition to magnesium's tocolytic and neuroprotective properties, it also has free radical reducing effects. The aim of the present study was to demonstrate whether magnesium sulfate could have protective effect on fetal rat skin in intrauterine ischemia reperfusion (I/R) injury. Fetal skin ischemia was induced by clamping the utero ovarian arteries bilaterally for 30 min, and reperfusion was achieved by removing the clamps for 60 min in 19-day pregnant rats. Magnesium Sulfate (MgSO(4)) was given to pregnant rats 20 min before I/R injury at the dose of 600 mg/kg in magnesium treatment group. No ischemia reperfusion was applied to control and sham-operated groups. Lipid peroxidation from the skin tissues was determined as thiobarbituric acid reactive substances (TBARS). Myeloperoxidase (MPO) activity was determined for neutrophil activation. The results showed that the levels of TBARS and MPO increased significantly in the fetal rat skin after I/R injury compared to control group. Levels of TBARS and MPO were significantly lower than those of I/R group in Magnesium-treated group. In conclusion, intrauterine ischemia-reperfusion may produce considerable fetal skin injury. Increased TBARS and MPO activity can be inhibited by magnesium treatment. This suggests that magnesium treatment may have protective effect on fetal rat skin in intrauterine I/R injury. PMID- 22310736 TI - Breast cancer: Anastrozole sets the STAGE for premenopausal women. PMID- 22310735 TI - Inflammation and fibrogenesis in steatohepatitis. AB - Nonalcoholic fatty liver disease consists of a range of disorders characterized by excess accumulation of triglyceride within the liver. Whereas simple steatosis is clinically benign, nonalcoholic steatohepatitis (NASH) often progresses to cirrhosis. Inflammation and fibrogenesis are closely inter-related and are major targets of NASH research. Experimental data have shown that inflammation in NASH is caused by insulin resistance, systemic lipotoxicity due to overnutrition, lipid metabolites, the production of proinflammatory cytokines and adipokines by visceral adipose tissue, gut-derived bacteria, and oxidative stress. In NASH associated fibrosis, the principal cell type responsible for extracellular matrix production is recognized as the hepatic stellate cell. Although the fibrotic mechanisms underlying NASH are largely similar to those observed in other chronic liver diseases, the altered patterns of circulating adipokines, the generation of oxidative stress, and the hormonal profile associated with the metabolic syndrome might play unique roles in the fibrogenesis associated with the disease. Information on the basic pathogenesis of NASH with a focus on the generation of inflammation and fibrosis will be discussed. PMID- 22310737 TI - Lung cancer: Practical assay to predict survival. PMID- 22310738 TI - Gynecological cancer: DOvE pilots its way to intriguing results. PMID- 22310739 TI - Targeted therapies: Smart tumor, smarter treatment. PMID- 22310741 TI - Multidetector computed tomography virtual cystoscopy: an effective diagnostic tool in patients with hematuria. AB - OBJECTIVE: To evaluate the efficacy and the potential use of multidetector computed tomography virtual cystoscopy (MDCT-VC) in patients with gross hematuria. METHODS: A total of 32 patients underwent MDCT-VC, cystoscopy, and a cytologic examination. The slice thickness of MDCT was 1 mm. Bladder distension was done with room air. The data were converted into 3-dimensional virtual reconstructive models. The data sets were reviewed independently by 2 experienced radiologists. Tumors confined to the mucosa, infiltrating the muscularis, and transmural tumors were distinguished. RESULTS: VC showed a sensitivity and specificity of 100%. The radiologic accuracy regarding T stage correlated in 87.5%. MDCT-VC identified 21 bladder lesions suspicious for bladder cancer in 18 patients. The histologic results showed 22 patients with bladder lesions, 18 were diagnosed with transitional cell carcinoma of the bladder, 3 had bladder endometriosis, and 1 had an infiltrating colon cancer. Four patients had concomitant carcinoma in situ lesions, which were not seen completely with MDCT VC. However, cytology was positive in those cases. Ten patients did not have any tumor signs on VC and the subsequent conventional cystoscopy did not bring any change to the initial tumor-free diagnosis of VC. CONCLUSION: MDCT-VC combined with urine cytology is a good alternative to conventional cystoscopy for patients with painless gross hematuria. It should be used as a decision-making aid to identify patients who will benefit from additional cystoscopic examination. Future developments should focus on the visibility of sessile and carcinoma in situ lesions. PMID- 22310742 TI - Editorial comment. PMID- 22310744 TI - Editorial comment. PMID- 22310746 TI - Modified transurethral incision for primary bladder neck obstruction in women: a method to improve voiding function without urinary incontinence. AB - OBJECTIVE: To describe the modified surgical technique and report the long-term outcomes of modified transurethral incision for the treatment of primary bladder neck obstruction in women. METHODS: A total of 30 women were diagnosed with primary bladder neck obstruction from the videourodynamic study findings according to the Blaivas-Groutz nomogram for female bladder outlet obstruction. Patients with neurogenic, traumatic, anatomic, or iatrogenic causes of obstruction were excluded. The transurethral incision of the bladder neck was performed in all patients, with the modification of incising at 4 different sites on the bladder neck, at the 3-, 6-, 9-, and 12-o'clock positions. The urodynamic results and clinical improvement in voiding symptoms were assessed before surgery and 3, 48, and 60 months after treatment. RESULTS: Follow-up data were available for 30 (100%), 28 (93%), and 25 (83%) of the 30 patients at 3, 48, and 60 months postoperatively, respectively. During the 5-year follow-up, the mean International Prostate Symptom Score decreased from 23.3 to 5.9. The mean quality of life scores decreased from 4.4 to 2.1. The mean peak urinary flow rate increased from 7.61 to 17.53 mL/s. The mean postvoid residual urine volume decreased from 185.11 to 28.75 mL. The mean voiding detrusor pressure decreased from 62.12 to 21.92 cm H2O. All 25 patients had improvement in both objective and subjective voiding functions 5 years after this modified treatment. Only 1 woman (3%) had mild stress incontinence postoperatively and was cured after the patient performed levator ani exercises. CONCLUSION: The modified transurethral bladder neck incision is effective in the long term in relieving voiding difficulties owing to primary bladder neck obstruction in women without urinary incontinence. PMID- 22310747 TI - Editorial comment. PMID- 22310748 TI - Adoption of laparoscopic radical nephrectomy in the state of Washington. AB - OBJECTIVE: To examine state-wide trends in adoption of laparoscopic radical nephrectomy (LRN). Open radical nephrectomy and LRN confer equivalent long-term oncological outcomes, yet LRN usage has not increased analogous to diffusion of laparoscopy in other fields. MATERIAL AND METHODS: From the Washington State Comprehensive Hospital Abstract Reporting System, we identified patients who underwent ORN and LRN from 1998 to 2007. Number of LRNs was examined for each hospital state-wide. Length of stay outcomes were examined, and multivariate models were created to examine characteristics of LRN patients and of patients who received care at high-volume LRN hospitals (HiLap). RESULTS: The proportion of nephrectomies performed laparoscopically increased 27%. In 1998, 7 hospitals (12%) performed>=1 LRN compared with 36 hospitals (61%) in 2007. Four HiLap hospitals accounted for 61% of the increase in LRN from 1998-2002, and 36% of the increase overall. Women (OR 1.15, 95% CI 1.00-1.33) and healthier patients (OR 1.52, 95% CI 1.28-1.82 for patients with Charlson 0 vs >=2) were more likely to undergo LRN. Mean length of stay for nephrectomies was shorter at HiLap hospitals (P=.04 for 1998-2002, P<.001 for 2003-2007). CONCLUSIONS: Uptake of LRN in Washington state parallels national trends; however, the proportion of LRN is lower than expected. A handful of hospitals account for the majority of the increase in LRN. The quality of nephrectomy care may be better at these centers. Barriers exist that prevent LRN adoption even after a trial case. Dissemination of the processes or personnel associated with use of LRN may increase the proportion of patients undergoing LRN. PMID- 22310749 TI - Blood transfusions in radical prostatectomy: a contemporary population-based analysis. AB - OBJECTIVE: To examine the homologous blood transfusion (HBT), autologous blood transfusion (ABT) and intraoperative blood conservation technique (IOBCT) rates and trends at open (ORP) and minimally invasive radical prostatectomy (MIRP). METHODS: The Nationwide Inpatient Sample was queried. Multivariable logistic regression models focused on all three transfusion types. Covariables consisted of procedure specific annual hospital caseload (AHC), year of surgery, age, Charlson Comorbidity Index, and region. RESULTS: Overall, 119,966 patients underwent radical prostatectomy between 1998 and 2007. The HBT, ABT, and IOBCT rates were 6.2%, 6.0%, and 1.2%, respectively. HBT rates ranged from 5.1-5.1% between 1998 and 2007 (P=.49) vs 9.4-2.7% (P<.001) for ABT vs 1.9-0.9% (P=.003) for IOBCT in the same time period, respectively. In multivariable analyses, ORP patients treated at intermediate (odds ratio [OR] 1.48, P=.003) and low (OR 2.73, P<.001) AHC institutions were more likely to receive an HBT than ORP patients treated at high AHC institutions. Conversely, MIRP patients treated at high (OR 0.46, P=.040), intermediate (OR 0.27, P=.001), and low (OR 0.59, P=.015) AHC institutions were less likely to receive an HBT than ORP patients treated at high AHC institutions. CONCLUSION: Our results indicate that the overall transfusion rate at radical prostatectomy decreased within the last decade because of a substantial decline in ABT use. Moreover, MIRP protects from HBT, even when performed at low AHC Centers. PMID- 22310750 TI - Editorial comment. PMID- 22310752 TI - Renal function after partial nephrectomy: effect of warm ischemia relative to quantity and quality of preserved kidney. AB - OBJECTIVE: To evaluate the effects of warm ischemia time (WIT) and quantity and quality of kidney preserved on renal functional recovery after partial nephrectomy (PN). The effect of WIT relative to these other parameters has recently been challenged. METHODS: We identified 362 consecutive patients with a solitary kidney who had undergone PN using warm ischemia. Multivariate models with multiple imputations were used to evaluate the associations with acute renal failure and new-onset stage IV chronic kidney disease (CKD). RESULTS: The median WIT was 21 minutes (range 4-55), the median percentage of kidney preserved was 80% (range 25%-98%), and the median preoperative glomerular filtration rate (GFR) was 61 mL/min/1.73 m2 (range 11-133). Postoperative acute renal failure occurred in 70 patients (19%). Of the 226 patients with a preoperative GFR>30 mL/min/1.73 m2, 38 (17%) developed new-onset stage IV CKD during follow-up. On multivariate analysis, the WIT (P=.021), percentage of kidney preserved (P=.009), and preoperative GFR (P<.001) were significantly associated with acute renal failure, and only the percentage of kidney preserved (P<.001) and preoperative GFR (P<.001) were significantly associated with new-onset stage IV CKD during follow up. Using our previously published cutpoint of 25 minutes, a WIT of >25 minutes remained significantly associated with new-onset stage IV CKD in a multivariate analysis adjusting for the quantity and quality factors (hazard ratio 2.27, P=.049). CONCLUSION: Our results have validated that the quality and quantity of kidney are the most important determinants of renal function after PN. In addition, we have also demonstrated that the WIT remains an important modifiable feature associated with short- and long-term renal function. The precision of surgery, maximizing the amount of preserved, vascularized parenchyma, should be a focus of study for optimizing the PN procedure. PMID- 22310753 TI - Editorial comment. PMID- 22310755 TI - Understanding the role of percutaneous biopsy in the management of patients with a small renal mass. AB - OBJECTIVE: To evaluate patient and tumor characteristics associated with percutaneous renal mass biopsy (RMB) among patients with small renal masses (SRMs) and assessed the impact on clinical decision-making. MATERIALS AND METHODS: For 204 consecutive patients presenting with a clinical stage T1 renal mass at our institution, we collected data regarding patient demographics, comorbidity, renal function, anatomic factors, and treatment plan. We then assessed the association between these characteristics and receipt of RMB, and between biopsy results and initial treatment decision. RESULTS: Among 204 patients, 78 (38%) received RMB. Of the demographic and physiological parameters, only non-Caucasian race and family history of renal cell carcinoma were associated with biopsy (P<.05). In contrast, RMB was significantly associated with several anatomic factors, including larger tumor size, solitary kidney, juxta-hilar tumor location, greater body mass index (BMI), and high-complexity nephrometry score (P<.05). On multivariable analysis, only BMI>25 kg/m2, juxta hilar location, and high-complexity nephrometry score remained significantly associated with RMB (P<.05). Biopsy was performed in a greater proportion of patients who ultimately underwent radical nephrectomy vs nephron-sparing surgery (NSS) (P=.04). Furthermore, RMB results directly impacted treatment, with active surveillance more frequent among patients with benign or favorable histology and surgical management more common among patients with more aggressive disease (P<.001). CONCLUSION: At our institution, one-third of patients presenting with a SRM undergo RMB, most commonly among patients with complicated anatomic and/or tumor considerations. Because these factors may limit the feasibility of NSS, biopsies are being used to guide decision-making aimed at minimizing total kidney loss. PMID- 22310756 TI - Editorial comment. PMID- 22310759 TI - Editorial comment. PMID- 22310760 TI - Tubularized incised plate repair for penoscrotal hypospadias: role of surgeon's experience. AB - OBJECTIVE: To give a retrospective analysis of factors affecting outcome of tubularized incised plate (TIP) repair for penoscrotal hypospadias. METHODS: Data of all patients who underwent TIP repair for penoscrotal hypospadias by a single surgeon were retrieved. Follow-up was carried out every 3 months within the first year and annually thereafter. Repairs were divided into 2 groups: Group 1 included surgeries performed in the first 2 years after fellowship training, and group 2 included repairs performed afterward. Chi-square test was used for statistical analysis. Statistical significance was defined as P<.05. RESULTS: Data for 90 patients were retrieved for july 2001 through march 2009: Group 1 included 20 patients and group 2 included 70. The neourethra was covered with spongioplasty in 25 and dartos flap in 65. The overall success rate was 86%. Group 2 patients showed a statistically significant higher success rate of 91% compared with only 65% for group 1. Use of dartos flap was associated with statistically significant higher success (92%) compared with coverage of the neourethra with spongioplasty (68%). In group 1, use of dartos flap was associated with statistically significant better success (82% vs 33%). In group 2 patients, use of dartos flap showed no statistically better success (94% vs 81%). CONCLUSIONS: TIP is a valid procedure for repair of penoscrotal hypospadias with chordee<30 degrees. The overall success (86%) is satisfactory. Surgeon's experience is the pillar for better success. PMID- 22310762 TI - Editorial comment. PMID- 22310763 TI - Editorial comment. PMID- 22310765 TI - Prevention of wrong site surgery during upper tract endoscopy. AB - OBJECTIVE: To evaluate the use of radiopaque stickers during endoscopic surgical cases to prevent wrong side surgery. METHODS: We used radiopaque markers before planned endoscopic surgery to ensure correct side surgery. These markers are labeled "R" and "L" and are identifiable during fluoroscopy. RESULTS: These markers were a valuable tool to prevent wrong side endoscopic upper tract procedures. They were also well-accepted by patients at their preoperative surgical verification process. CONCLUSION: Radiopaque stickers can assist in the prevention of wrong side surgery during upper tract endoscopic procedures. PMID- 22310766 TI - Modified surgical technique for the management of renal cell carcinoma with level I or II tumor thrombus. AB - OBJECTIVE: To describe a modified open surgical technique for the resection of renal cell carcinoma with level I or II tumor thrombus. METHOD: In our modified technique, the renal artery is ligated early and the tumor thrombus is secured ahead of kidney mobilization by either milking into the renal vein or with extirpation from the inferior vena cava. We retrospectively studied patients who were managed with this technique. RESULTS: Between September 2006 and June 2010, 20 patients with a median age of 65 years underwent surgery for renal cell carcinoma with level I (n=15) or II (n=5) tumor thrombus using the modified technique. Median blood loss was 275 mL with 75% of patients requiring at least 1 transfused unit of blood. No case was complicated by an intraoperative tumor embolism. Following surgery, patients stayed a median of 5 days in the hospital and none experienced a perioperative complication. CONCLUSION: The described surgical technique allows for the safe and effective resection of renal cell carcinoma with level I or II tumor thrombus. This technique enables vascular control of the inferior vena cava with a minimal risk of tumor embolization. PMID- 22310767 TI - Editorial comment. PMID- 22310769 TI - Re: Breyer et al.: Use of Google insights for search to track seasonal and geographic kidney stone incidence in the United States. (Urology 2011;78:267 271). PMID- 22310770 TI - Re: Graft reconstruction of inferior vena cava for renal cell carcinoma stage pT3b or greater. (Urology 2011;78:838-843). PMID- 22310772 TI - Re: Samplaski et al.: Inclusion of erectile domain to UPOINT phenotype does not improve correlation with symptom severity in men with chronic prostatitis/chronic pelvic pain syndrome. (Urology 2011;78:653-658). PMID- 22310774 TI - Characterization of hydrogen sulfide and its synthases, cystathionine beta synthase and cystathionine gamma-lyase, in human prostatic tissue and cells. AB - OBJECTIVE: To investigate hydrogen sulfide and its synthases, cystathionine beta synthase (CBS) and cystathionine gamma-lyase (CSE), in human prostatic tissue and cells. METHODS: CBS and CSE in human prostatic tissue and cells were located using immunostaining. Western blot and a sulfur-sensitive electrode were used to evaluate the expression levels and catalytic activity of CBS and CSE. We analyzed the association between dihydrotestosterone-added or hormone-reduced medium induced CBS/CSE protein levels with androgen receptor levels in prostate cancer lines. All experiments were repeated >=3 times. RESULTS: Endogenous hydrogen sulfide and its synthases existed in various areas of human prostatic tissue and cells. Cell activity and CBS/CSE protein levels were greatest in the androgen dependent prostate cancer cell LNCaP among all cells and downregulated by dihydrotestosterone. CONCLUSION: Hydrogen sulfide and its synthases in human prostatic tissue and cells were modulated by dihydrotestosterone, which could suggest a potential therapy for prostatic disease. PMID- 22310775 TI - Increased cell apoptosis of urothelium mediated by inflammation in interstitial cystitis/painful bladder syndrome. AB - OBJECTIVE: To investigate whether bladder inflammation could directly modulate the signaling pathway of increased urothelial cell apoptosis in interstitial cystitis/painful bladder syndrome (IC/PBS). Chronic inflammation and impaired urothelial homeostasis are possible pathogenesis of IC/PBS. METHODS: A total of 29 patients with IC/PBS and 5 control patients were enrolled in the present study. Double stain, protein array analysis, and Western blotting were performed to analyze the alterations of caspase 3, Bad, Bax, phospho-p53, phospho-p38alpha, and tumor necrosis factor-alpha (TNF-alpha) in bladder mucosa specimens from patients with IC/PBS and control patients. The intensities of the proteins in the arrays and Western blots were quantified using ImageJ processing. Inflammatory molecule-treated urothelial cells were analyzed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining and Western blotting for the level of molecules involved in apoptosis. RESULTS: Phospho-p38 and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling double staining indicated that inflammatory and apoptotic events coexisted in the IC/PBS bladder. Protein-antibody array analysis showed that several inflammatory molecules were increased in the IC/PBS samples. We also found that the levels of pro-apoptotic proteins, including phospho-p53 (Ser 15), Bad, Bax, and cleaved caspase-3 were significantly increased in the IC/PBS bladders. These results were confirmed by immunoblotting and suggested that the tissue damage and abnormal urothelium in the IC/PBS bladder might be regulated concurrently by inflammatory signals, such as p38 mitogen-activated protein kinase and TNF-alpha. The in vitro analysis also showed that the apoptotic process could be induced by TNF-alpha treatment and anisomycin stimulation in normal urothelial cells. CONCLUSION: Apoptosis of urothelial cells in patients with IC/PBS could result from upregulation of inflammatory signals, including p38 mitogen-activated protein kinase and TNF-alpha. PMID- 22310776 TI - Hepatitis C: epidemiology, diagnosis, natural history and therapy. AB - With an estimated prevalence of 3% in the world population (around 170 million infected individuals worldwide), hepatitis C virus (HCV) heavily burdens public health. Even though the incidence of new infections is declining, at least in industrialized countries where they are mainly restricted to intravenous drug users, morbidity and mortality (which means also HCV-induced costs) associated with HCV infection are expected to increase over the next decade. Models suggest that the incidence of hepatocellular carcinoma and HCV-related mortality will still increase until about 2015. The prevalence of the disease, the risk of progression of fibrosis to cirrhosis or hepatocellular carcinoma, mainly but not only in patients with liver comorbidities such as metabolic syndrome and/or heavy alcohol intake, evidences: (1) the need for a screening of chronic HCV infection as defined by both anti-HCV antibodies and detectable HCV RNA, (2) the evaluation of the extrahepatic (cryoglobulinemia-related vasculitis) or liver impact of chronic infection (by liver biopsy or noninvasive markers of fibrosis) and (3) the discussion of an antiviral treatment which is mainly the combination of pegylated interferon (one weekly subcutaneous injection) and ribavirin, a nucleosidic analogue with a twice daily oral intake. This 'standard of care' results in a mean of 60% of sustained virologic response corresponding to viral eradication, which allows the inactivation of necroinflammation and the remodeling of fibrosis. New antiviral treatments (direct-acting anti-virals like protease NS3/4, polymerase NS5B, NS5A, entry inhibitors or other drugs like cyclophilin inhibitors, new interferons, immune modulators or therapeutic vaccine) are being rapidly developed (the approval of the first generation protease inhibitors is expected for spring 2011). The next step appears to be the combination of these oral drugs allowing a better safety and efficacy of the treatment. PMID- 22310777 TI - Hepatitis C and renal disease: epidemiology, diagnosis, pathogenesis and therapy. AB - There is an increased evidence for the association between hepatitis C virus (HCV) infection and kidney diseases. Recent epidemiological studies strongly suggest that HCV infection is a risk factor for proteinuria and/or impaired renal function. Type I membranoproliferative glomerulonephritis (MPGN) associated with type II cryoglobulinemia is the most frequent renal disease, and non cryoglobulinemic MPGN and membranous glomerulonephritis are less frequently associated with active HCV infection. The pathogenesis of these lesions are related to the deposition of immune complexes in the glomeruli, and recently it has been described that toll-like receptor 3 could have a pathogenic role establishing a link between viral infection and glomerulonephritis. Patients with HCV-related glomerulopathies should be treated with angiotensin-converting enzyme inhibitors in association or not with angiotensin receptor blockers, as well as with anti-HCV therapy. The latter relies on a combined antiviral therapy of standard or pegylated interferon-alpha and ribavirin. We recommend the treatment of patients for at least 48 weeks, and the continuation of antiviral therapy, even in the absence of a decrease in HCV RNA concentration of 2-log at week 12. Ribavirin doses should be adapted according to creatinine clearance in order to avoid its main side effect, i.e. hemolytic anemia. Combined antiviral therapy and immunosuppression (cyclophosphamide or rituximab with steroids) may be the treatment of choice for patients with severe renal disease, i.e. nephrotic syndrome and/or progressive renal failure, or diseases that are refractory to anti-HCV therapy alone. PMID- 22310778 TI - Hepatitis C-induced renal disease in patients with AIDS: an emergent problem. AB - Cryoglobulinemic membranoproliferative glomerulonephritis (MPGN) is the more characteristic renal disease associated with hepatitis C virus (HCV) infection. Patients infected with human immunodeficiency virus (HIV) can present, in addition to HIV-associated nephropathy, different types of immune complex glomerulonephritis, including MPGN, IgA nephropathy, non-collapsing focal segmental glomerulosclerosis, membranous nephropathy and lupus-like glomerulonephritis. On the other hand, the incidence of hypertensive nephrosclerosis, diabetic nephropathy and decreased renal function similar to that of elderly patients is increasingly recognized among HIV-infected patients. In spite of the fact that HCV coinfection in HIV patients is a very common problem, affecting approximately 30% of HIV-infected patients, information about the role of HCV in renal diseases of HIV-infected patients is scant. A large proportion of HIV patients with glomerular diseases are coinfected with HCV, and the latter is likely the responsible agent in those cases of cryoglobulinemic MPGN reported in HIV-infected patients. Participation of HCV in other types of HIV-related glomerular diseases is uncertain. Patient and renal survival in glomerular diseases of patients coinfected with HIV and HCV is very poor, but some studies suggest that antiretroviral therapy might change this dismal prognosis. Information about the effect of specific anti-VHC therapy or immunosuppressive agents in these patients is very limited. PMID- 22310779 TI - Hepatitis C in hemodialysis: epidemiology and prevention of hepatitis C virus transmission. AB - Hemodialysis (HD) patients were recognized as a high risk group for hepatitis C virus (HCV) infection almost immediately after the identification of HCV in 1989. Both transfusional and nosocomial transmission of HCV were then relatively frequent in HD. The dramatic reduction in transfusional transmission of HCV in the 1990s soon underlined the strongly suspected nosocomial risk. Multiple molecular virology reports eventually demonstrated patient to patient transmission. The reinforcement of hygienic precautions and/ or isolation strategies was the main subsequent step taken by most HD units. Both incidence and prevalence of HCV then decreased substantially in most western HD units. Currently, incidence is much lower whereas prevalence is largely influenced by the rate of acquisition of HCV prior to starting HD (be it in the remote past). Still, the risk of occasional nosocomial transmission remains. The actual application of basic hygienic precautions remains the cornerstone of the prevention of HCV nosocomial transmission, as reviewed in the recently published KDIGO guidelines on HCV in CKD. PMID- 22310780 TI - Hepatitis C-related liver disease in dialysis patients. AB - Hepatitis C virus (HCV) remains the most common cause of liver damage in patients with chronic kidney disease including patients on long-term dialysis. The natural history of HCV infection in patients with chronic kidney disease is not fully elucidated despite the adverse effect of HCV infection on survival in patients receiving long-term dialysis. A recent meta-analysis of seven observational studies (11,589 patients on dialysis) reported that the summary estimate for adjusted relative risk (all-cause mortality) with anti-HCV antibody was 1.34 with a 95% confidence interval of 1.13-1.59. As a cause of death, hepatocellular carcinoma and liver cirrhosis were significantly more frequent among anti-HCV positive than -seronegative dialysis patients; the summary estimate for unadjusted liver-related mortality risk was 5.89 (95% confidence interval 1.93 17.99). Impairment of quality of life due to HCV has also been suggested to explain the diminished survival in this setting. Recent data also suggest an excess risk of cardiovascular disease in HCV-infected dialysis patients. Recent evidence supports the notion that the progression of HCV-related liver disease is probably slower in the dialysis population than in non-uremic patients despite the immune compromise conferred from chronic uremia; numerous mechanisms have been mentioned to explain it. It appears that the hemodialysis procedure per se reduces the HCV viral load, and the mechanisms by which this phenomenon occurs remain largely speculative - the intradialytic production of interferon-alpha, hepatocyte growth factor, or other cytokines provided with antiviral activities have been implicated. This is an area of intense investigation, and further studies are indicated. PMID- 22310781 TI - Treatment of hepatitis C in dialysis patients. AB - Chronic infection with hepatitis C virus (HCV) is a major problem affecting a significant percentage of patients with end-stage renal failure (ESRD), with a negative impact on patient survival, and associated with accelerated progression of liver damage after undergoing a kidney transplant. After acute HCV infection, HCV infection becomes chronic in around 80% of patients and progresses to cirrhosis in about 20% of cases at 20 years of evolution. Treatments with interferon (IFN-alpha2a) and pegylated IFN are currently the only treatments that achieve a cure rate of about 30-45% of ESRD patients with chronic HCV infection. The combination with ribavirin (RBV) in the general population has improved the results, with a sustained virological response between 50% (genotype 1 and 4) and 80% (genotype 2 and 3); however, the poor tolerance to RBV in ESRD patients makes this treatment difficult in dialysis patients. Indication of antiviral treatment in HCV-positive patients on dialysis should be individualized. All HCV-positive candidates for kidney transplantation should be assessed to receive antiviral treatment before transplantation given the increased life expectancy compared to other HCV-positive patients on dialysis, the increased risk of progression of liver disease with immunosuppressive therapy and the inability to receive IFN therapy after renal transplantation. PMID- 22310782 TI - Selection and management of hepatitis C virus-infected patients for the kidney transplant waiting list. AB - Hepatitis C virus (HCV) infection has been demonstrated to be present in a significant number of ESRD patients, and infection with this virus has been shown to have a detrimental impact on patient survival in both the dialysis and transplant patient populations. Studies have shown that 10-25% of pre-kidney transplant candidates have advanced liver injury with stage 3 or 4 disease (cirrhosis) when biopsied during the pretransplant evaluation. To identify those patients in whom a more extensive workup is required, all transplant candidates should be initially screened for anti-HCV antibody and/or active viremia using nucleic acid testing depending on the prevalence of HCV in the community. Although efforts have been directed at finding a reliable noninvasive marker of advanced liver disease in this patient population, liver biopsy remains the gold standard and should be obtained during the pretransplant evaluation in all patients determined to have active HCV infection. There is general agreement that patients with established or decompensated cirrhosis should be referred to the liver transplant team for consideration of combined liver-kidney transplantation. Patients on the kidney transplant waiting list should be monitored on a regular basis to identify those who might have progressive liver disease. This is especially relevant in an era when waiting times at some centers approach 5-7 years. There is no consensus on whether the pretransplant patient with active HCV viremia should be treated with antiviral agents prior to transplant. There is some largely anecdotal evidence that inducing a sustained virological response prior to transplant might lessen the risk of developing posttransplant diabetes and immune complex-mediated glomerular disease in the allograft. Whereas there is good evidence that the majority of patients achieving a sustained virological response prior to transplant do not relapse following the introduction of immunosuppression, there are limited data as to whether this has a positive impact on the progression of liver injury. Several studies have demonstrated that the use of interferon in the posttransplant setting is associated with an increased risk of allograft rejection; thus, any efforts to eradicate HCV should be focused on the pretransplant period. In summary, a thorough screening process to identify HCV infection in the pre-kidney transplant candidate, including the staging of liver disease in those determined to have viremia, is necessary so that the most appropriate treatment plan can be developed for each patient. PMID- 22310783 TI - Kidney transplantation in the patient with hepatitis C virus infection. AB - Liver disease is an important comorbidity following kidney transplantation, and hepatitis C virus (HCV) infection has been demonstrated to be the leading cause of this complication. Anti-HCV-positive kidney transplant recipients have a higher risk for developing proteinuria, chronic rejection, infections, glomerulonephritis and new-onset diabetes after transplantation (NODAT). Together with progressive liver disease in some patients, these complications all contribute to inferior patient and graft survival rates observed in anti-HCV positive patients when compared to their uninfected counterparts. The increased mortality in the anti-HCV-positive cohort is largely as a result of a higher incidence of cardiovascular disease, liver disease and infections. HCV can also contribute to the development of some extrahepatic neoplasias, such as posttransplant lymphoproliferative disease. HCV infection is also an independent risk factor for graft loss, likely contributed to by the development of NODAT, chronic rejection/transplant glomerulopathy and HCV-related glomerulonephritis. Despite the increased comorbidities associated with kidney transplant in the HCV infected patient, transplantation offers the best long-term outcomes for the end stage renal disease patient with HCV infection. Finally, several interventions designed to minimize the potentially adverse consequences of HCV infection should be considered in the posttransplant setting. Adjustment of immunosuppression and careful follow-up in the outpatient clinic for early detection of proteinuria, renal insufficiency, infection, NODAT, neoplasia or worsening of liver disease are important components of the posttransplant care of the patient with HCV infection. PMID- 22310784 TI - Treatment of hepatitis C virus infection after kidney transplantation. AB - The prevalence of chronic hepatitis C virus (HCV) infection after kidney transplantation (KT) varies a lot from one country to another. In the setting of (powerful) immunosuppression, HCV replication can sharply increase, thereby leading to potential severe HCV-related liver damage such cirrhosis or fibrosing cholestatic hepatitis. In the setting of KT, alpha-interferon (alpha-IFN) therapy alone has been associated with a very low sustained virological response (SVR), and a poor tolerance, particularly with regard to the kidney allograft, i.e. it induces acute rejection. The combined use of alpha-IFN plus ribavirin leads to a greater rate of SVR, but randomized clinical trials are missing in order to evaluate its safety with respect to the allograft function. Ribavirin monotherapy, or ribavirin plus amantadine therapy are not able to induce SVR; ribavirin may have an effect upon HCV-related proteinuria. Finally, it seems advisable to try and eradicate HCV infection prior to KT, i.e. while the patient is on dialysis therapy. After KT, alpha-IFN plus ribavirin therapy could be attempted only in those patients developing rapid cirrhosis or in those developing fibrosing cholestatic hepatitis or in those having de novo cryoglobulinemic glomerulonephritis within the allograft. PMID- 22310785 TI - Immunosuppression in hepatitis C virus-infected patients after kidney transplantation. AB - Hepatitis C virus (HCV) infection is an important health problem in kidney transplant recipients with a significantly higher prevalence than in the general population. Kidney transplantation remains the treatment of choice for most HCV infected patients with end-stage kidney disease, in spite of lower patient and graft survival as compared to HCV-negative patients. Immunosuppression likely has significant consequences on HCV replication and/or disease after transplantation. However, determining the best immunosuppressive strategies after kidney transplantation in the presence of HCV infection remains challenging. The use of induction therapy is not contraindicated, and a short-course induction may actually be beneficial in HCV-infected kidney transplant recipients. Corticosteroid withdrawal may be an acceptable option in HCV-infected patients with specific comorbidities such as diabetes mellitus or osteoporosis. The best calcineurin inhibitor to be used in HCV-infected patients remains to be determined, as there is a lack of large controlled trials addressing this particular issue. Overall, immunosuppressive regimens need to be individualized according to clinical parameters other than HCV, such as the patient's immunological risk and other comorbidities. In conclusion, there is a need for prospective controlled studies to define the optimal immunosuppressive regimen in HCV-infected kidney transplant recipients. PMID- 22310786 TI - Impact of extrahepatic complications (diabetes and glomerulonephritis) associated with hepatitis C virus infection after renal transplantation. AB - Hepatitis C virus (HCV) infection is associated with some extrahepatic complications, like diabetes, cryoglobulinemia, and membranoproliferative glomerulonephritis. Each of these complications has important implications in the renal allograft recipient. Hence, HCV infection is strongly associated with a lower patient and graft survival in renal transplantation. The increased risk of death in HCV-infected renal allograft recipients has been attributed to cardiovascular mortality, linked someway to the insulin resistance and high risk of new-onset diabetes, rather than to the progression of HCV-related liver disease. On the other hand, graft survival is hampered by the occurrence of de novo HCV-related glomerulonephritis and the higher risk of chronic humoral rejection in this population. PMID- 22310787 TI - Renal transplantation from donors with a positive serology for hepatitis C. AB - Transplantation of kidneys from donors with a positive serology for hepatitis C virus (HCVD+) remains controversial as made evident by wide variations in practice. Current knowledge derived from unicenter and registry experiences have demonstrated that the use of HCVD+ kidneys in HCV+ recipients seems to be safe in the long-term. This information, summarized in this chapter, has provided the basis for internationally agreed recommendations which limit the use of these kidneys for transplantation in recipients with a positive HCV RNA while on the waiting list and consenting in advance. Avoiding superinfection might require matching donors and recipients based on the involved HCV genotype, an approach limited by obvious time constraints. Because the incidence and prevalence of HCV infection is decreasing and there is a proactive treatment of patients with end stage renal disease and HCV infection before being included on the waiting list, kidneys from HCVD+ are becoming surplus organs due to the lack of appropriate recipients. The underutilization of these kidneys at a moment of dramatic organ shortage requires organizational measures, including the offer of these kidneys for preemptive transplantation, besides the need of reviewing the evidence driving local criteria. PMID- 22310788 TI - NADPH oxidase mediated oxidative stress in hepatic fibrogenesis. AB - NADPH oxidase (NOX) is a multicomponent enzyme complex that generates reactive oxygen species (ROS) in response to a wide range of stimuli. ROS is involved as key secondary messengers in numerous signaling pathways, and NADPH oxidases complex has been increasingly recognized as key elements of intracellular signaling of hepatic fibrogenesis. In the liver, NADPH oxidase is functionally expressed both in the phagocytic form and in the non-phagocytic form. The non phagocytic NADPH oxidase complex is structurally and functionally similar to the phagocytic NADPH, resulting in reduction of molecular oxygen to generate superoxide. There are six homologous NOX proteins in the non-phagocytic forms of NADPH oxidase. An emerging concept is that both phagocytic and nonphagocytic NADPH oxidase components in hepatic stellate cells (HSCs) mediate hepatic fibrosis, suggesting its potential role as a pharmacological target for anti fibrotic therapy. The molecular components and signaling pathways of various NADPH oxidase homologues that are critical for the fibrotic activity in HSCs need to be more clearly identified. PMID- 22310789 TI - A tool for communication with decision-makers: limitations and utilization of studies on cost of illness. PMID- 22310790 TI - Virologic response is not durable after adefovir discontinuation in lamivudine resistant chronic hepatitis B patients. AB - BACKGROUND/AIMS: We investigated the durability of the biochemical and virologic responses after adefovir (ADV) discontinuation in lamivudine-resistant (LMV-R) chronic hepatitis B (CHB) patients, and the outcomes of ADV discontinuation compared to that of ADV maintenance. METHODS: The indication for ADV treatment cessation was an undetectable level of hepatitis B virus (HBV) DNA documented on two occasions at least 6 months apart. All patients received additional ADV for at least 12 months after the confirmation of undetectable HBV DNA (Cobas TaqMan PCR assay, <70 copies/mL). Of 36 patients who had a sufficient ADV therapeutic effect, 19 discontinued ADV treatment, while the others maintained it. A virologic rebound was arbitrarily defined as the redetection of HBV DNA at a level higher than 10(5) copies/mL. RESULTS: In the ADV discontinuation group, ADV treatment and additional therapy were administered for medians of 33 months (range, 12-47 months) and 18 months, respectively. The patients were followed for a median of 12 months (range, 3-30 months) after ADV cessation. During that period, 18 of 19 patients (95%) experienced viral relapse. Viral rebound was observed in six patients (32%). However, 12 of 18 patients (67%) exhibited serum HBV DNA levels of less than (5) copies/mL. Biochemical relapses were observed in four of the six patients with viral rebound. In the ADV maintenance group, patients were treated for a median of 53 months (range, 31-85 months), and 9 patients (53%) experienced viral breakthrough. CONCLUSIONS: During short-term follow-up after ADV discontinuation, most patients (95%) exhibited viral relapse, whereas and viral breakthrough occurred in about half of patients (53%) maintained on ADV therapy. Therefore, the durability of virologic response after ADV discontinuation in LMV-R patients was unsatisfactory. In addition, and viral breakthrough was not infrequent in the ADV continuation group. PMID- 22310791 TI - Pretreatment serum HBsAg-to-HBV DNA ratio predicts a virologic response to entecavir in chronic hepatitis B. AB - BACKGROUND/AIMS: Decay of hepatitis B surface antigen (HBsAg) titers has previously been shown to be predictive of a virologic response (VR), especially during peginterferon-alpha therapy. However, the role of HBsAg levels in predicting a VR to nucleos(t)ide analog therapy has not yet been established. In this study we sought to determine whether the VR can be predicted from HBsAg titers in nucleos(t)ide-naive chronic hepatitis B (CHB) patients treated with entecavir. METHODS: CHB patients who started entecavir as an initial antiviral therapy were enrolled in this study. Serum hepatitis B virus (HBV) DNA, HBsAg, and alanine aminotransferase levels were measured every 3 months during treatment. A VR was defined as undetectable serum HBV DNA titer by real-time PCR assay (<60 IU/mL). RESULTS: Fifty-two patients were enrolled, and the median duration of treatment was 26 months (range 7-35 months). Forty-five patients achieved a VR; the cumulative VR rates at 3, 6, 12, and 24 months were 40%, 71.2%, 81.5%, and 88%, respectively. Baseline HBV DNA levels were significantly lower in patients with VR, whereas the HBsAg levels did not differ significantly between patients with or without VR. In a univariate analysis the cumulative VR rate was significantly higher in HBeAg negative patients and patients with an HBsAg/HBV DNA ratio above 0.56. However, in a multivariate analysis only an HBsAg/HBV DNA ratio above 0.56 was an independent predictor of VR (P=0.003). The area under the receiver operating characteristic curve was larger for the HBsAg/HBV DNA ratio than for either HBV DNA or HBsAg. CONCLUSIONS: Pretreatment HBsAg/HBV DNA ratio can predict a long-term VR to entecavir therapy in nucleos(t)ide-naive CHB patients. PMID- 22310792 TI - Socioeconomic costs of liver disease in Korea. AB - BACKGROUND/AIMS: This study analyzed the scale and trends of the social and economic costs of liver disease in Korea for the past 5 years. METHODS: The social aspects of socioeconomic costs were projected for viral hepatitis (B15 B19), liver cirrhosis, malignant neoplasm of the liver (C22) and other liver diseases (K70-K76), as representative diseases by dividing costs into direct and indirect from 2004 to 2008. Direct costs include hospitalization, outpatient, and pharmacy costs in the health-care sector, and transportation and caregiver costs. Indirect costs include the future income loss due to premature death and the loss of productivity resulting from absence from work. RESULTS: The social and economic costs of liver disease were projected to be KRW 5,858 billion in 2004, KRW 5,572 billion in 2005, KRW 8,104 billion in 2006, KRW 6,095 billion in 2007, and KRW 5,689 billion in 2008. The future income loss resulting from premature death is thus greatest, from 73.9% to 86.1%, followed by the direct medical costs, from 9.0% to 18.1%. The productivity loss resulting from absence from work accounts for 3.3-5.5%, followed by the direct nonmedical costs such as transportation and caregiver costs, at 1.5-2.5%. CONCLUSIONS: Among the socioeconomic costs of liver disease in Korea, the future income loss resulting from premature death is showing a decreasing trend, whereas direct medical costs are increasing dramatically. PMID- 22310793 TI - Chemical pleurodesis for the management of refractory hepatic hydrothorax in patients with decompensated liver cirrhosis. AB - BACKGROUND/AIMS: Hepatic hydrothorax in patients with decompensated liver cirrhosis is a challenging problem. Treatment with diuretics and intermittent thoracentesis can be effective in selected patients. However, there are few effective therapeutic options in patients who are intolerant of these therapies. This study investigated the clinical usefulness of chemical pleurodesis with or without video-assisted thoracoscopic surgery (VATS) for patients with refractory hepatic hydrothorax. METHODS: Eleven consecutive patients with refractory hepatic hydrothorax who underwent chemical pleurodesis with or without VATS between July 2007 and February 2011 were enrolled in this study. The medical records and radiologic imagings of these patients were thoroughly reviewed. RESULTS: The median number of chemical pleurodesis sessions performed was 3 (range: 2-10). Successful pleurodesis was achieved in 8 of the 11 patients (72.7%), 5 (62.5%) of whom remained asymptomatic and hydrothorax free for a median follow-up of 16 weeks (range: 2-52 weeks). Complications were low-grade fever/leukocytosis (n=11, 100%), pneumonia (n=1, 9.1%), pneumothorax (n=4, 36.4%), azotemia/acute renal failure (n=6, 54.6%), and hepatic encephalopathy (n=4, 36.4%). Five patients were suspected as having procedure-related mortality (45.5%) due to the occurrence of acute renal failure with hepatic failure. The overall survival was significantly longer in the success group than in the non-success group. CONCLUSIONS: Although chemical pleurodesis may improve the clinical symptoms and the radiologic findings in as many as 72.7% of patients with refractory hepatic hydrothorax, a significantly high prevalence of procedure-related morbidity and mortality hinders the routine application of this procedure for such patients. PMID- 22310794 TI - Differences in the patterns and outcomes of enhanced viral replication between hepatitis C virus and hepatitis B virus in patients with hepatocellular carcinoma during transarterial chemolipiodolization. AB - BACKGROUND/AIMS: Enhanced replication of hepatitis C virus (HCV) is well described in the setting of moderate to severe immunosuppression. The aims of this retrospective study were to determine the incidence of enhanced HCV replication in hepatocellular carcinoma (HCC) patients undergoing transarterial chemolipiodolization (TACL) and to identify the factors associated with enhanced replication of HCV. The clinical pattern of enhanced HCV replication was compared with hepatitis B virus (HBV) reactivation during TACL. METHODS: This study enrolled 49 anti-HCV-seropositive patients who were diagnosed with HCC between January 2005 and December 2010 and who underwent TACL using epirubicin and/or cisplatin with consecutive HCV RNA copies checked. For comparison, 46 hepatitis B surface antigen(1)-positive patients with HCC who were treated with TACL were also enrolled. The frequency, associated factors, and clinical outcomes of enhanced HCV replication were analyzed and compared with those of HBV reactivation during TACL. RESULTS: Enhanced replication of HCV occurred in 13 (26.5%) of the 49 anti-HCV-seropositive patients during TACL. Of these 13 patients, 4 developed hepatitis, but none of the subjects developed decompensation due to the hepatitis. No significant clinical factors for enhanced HCV replication during TACL were found. Compared with HBV reactivation, the frequency of hepatitis attributed to enhanced HCV replication was significantly lower than that for HBV reactivation (8.2% vs. 23.9%, P=0.036). CONCLUSIONS: TACL can enhance HCV replication; however, the likelihood of hepatitis and decompensation stemming from enhanced HCV replication was lower than that for HBV reactivation in patients undergoing TACL. PMID- 22310795 TI - Clinical features of acute viral hepatitis B in Korea: a multi-center study. AB - BACKGROUND/AIMS: The incidence of Hepatitis B has significantly declined since the introduction of an HBV vaccination program. The aim of this study was to investigate recent clinical features of acute viral hepatitis B (AVH-B) in Korea. METHODS: A total of 2241 patients with acute viral hepatitis were enrolled and their data were collected from nine medical-centers between January 2006 and December 2009. RESULTS: One hundred nineteen (5.3%) of the 2241 were diagnosed as AVH-B. Among 78 patients with AVH-B whose data were analyzed, 50 were male, and the mean age was 38.6 years. In an initial test, mean AST, ALT and total bilirubin levels were 1296.2 IU/L, 2109.6 IU/L and 9.3 mg/dl, respectively. Positivity frequencies for HBeAg and anti-HBe were 55.1% and 67.9%, respectively, and the mean HBV DNA level was 5.2 log10 copies/ml. The mean length of hospitalization was 11.6 days. During follow-up, AST, ALT and total bilirubin levels were normalized or near-normalized in all patients without serious complications. Sixty-three of 66 (95.4%) patients showed HBsAg loss and 37 (56.1%) patients showed HBsAg seroconversion. Only 3 patients (4.5%) showed persistent hepatitis B viremia. There was no case of death or liver transplantation. Nine patients (11.3%) had received anti-viral agents and their clinical outcomes were not significantly different from those of patients treated without antiviral agents. CONCLUSIONS: The prevalence of AVH-B among acute hepatitis patients is relatively low in Korea. AVH-B infection can be cured without complications in almost all patients, regardless of antiviral treatment. PMID- 22310796 TI - Osler-Weber-Rendu disease presenting with hepatocellular carcinoma: radiologic and genetic findings. AB - This is a case report of a 68-year-old man with hepatocellular carcinoma (HCC) accompanied by hereditary hemorrhagic telangiectasia (HHT), also known as Osler Weber-Rendu disease, and hepatic vascular malformation. HHT is an autosomal dominant disorder of the fibrovascular tissue that is characterized by recurrent epistaxis, mucocutaneous telangiectasias, and visceral arteriovenous malformations. HHT is caused by mutation of the genes involved in the signaling pathway of transforming growth factor-beta, which plays an important role in the formation of vascular endothelia. Hepatic involvement has been reported as occurring in 30-73% of patients with HHT. However, symptomatic liver involvement is quite rare, and the representative clinical presentations of HHT in hepatic involvement are high-output heart failure, portal hypertension, nodular regenerative hyperplasia, and symptoms of biliary ischemia. Some cases of HCC in association with HHT have been reported, but are very rare. We present herein the characteristic radiologic and genetic findings of HHT that was diagnosed during the evaluation and treatment of HCC. PMID- 22310797 TI - Metastatic hepatocellular carcinoma presenting as facial nerve palsy and facial pain. AB - Facial nerve palsy due to temporal bone metastasis of hepatocellular carcinoma (HCC) has rarely been reported. We experienced a rare case of temporal bone metastasis of HCC that initially presented as facial nerve palsy and was diagnosed by surgical biopsy. This patient also discovered for the first time that he had chronic hepatitis B and C infections due to this facial nerve palsy. Radiation therapy greatly relieved the facial pain and facial nerve palsy. This report suggests that hepatologists should consider metastatic HCC as a rare but possible cause of new-onset cranial neuropathy in patients with chronic viral hepatitis. PMID- 22310798 TI - Coinfection of hepatitis A virus genotype IA and IIIA complicated with autoimmune hemolytic anemia, prolonged cholestasis, and false-positive immunoglobulin M anti hepatitis E virus: a case report. AB - A 37-year-old male presented with fever and jaundice was diagnosed as hepatitis A complicated with progressive cholestasis and severe autoimmune hemolytic anemia. He was treated with high-dose prednisolone (1.5 mg/kg), and eventually recovered. His initial serum contained genotype IA hepatitis A virus (HAV), which was subsequently replaced by genotype IIIA HAV. Moreover, at the time of development of hemolytic anemia, he became positive for immunoglobulin M (IgM) anti-hepatitis E virus (HEV). We detected HAV antigens in the liver biopsy specimen, while we detected neither HEV antigen in the liver nor HEV RNA in his serum. This is the first report of hepatitis A coinfected with two different genotypes manifesting with autoimmune hemolytic anemia, prolonged cholestasis, and false-positive IgM anti-HEV. PMID- 22310799 TI - Biliary intraepithelial neoplasia: a case with benign biliary stricture. PMID- 22310800 TI - Biliary hamartoma presented as a single mass. AB - Usual biliary hamartomatosis presents as numerous small, non-enhancing nodules in liver. However, in some cases, it can presents as a single solid or cystic mass with various contrast enhancement pattern. PMID- 22310802 TI - Diversity of bacterial communities associated with the Indian Ocean sponge Tsitsikamma favus that contains the bioactive pyrroloiminoquinones, tsitsikammamine A and B. AB - Tsitsikamma favus is a latrunculid sponge endemic to the coast of South Africa that produces unique pyrroloiminoquinones known as tsitsikammamines. Wakayin and makaluvamine A are structurally similar to the tsitsikammamines and are the only pyrroloiminoquinones isolated from a source other than Porifera (namely a Fijian ascidian Clavelina sp. and a laboratory culture of the myxomycete Didymium bahiense, respectively). The source of the tsitsikammamines is hypothesised to be microbial, which could provide a means of overcoming the current supply problem. This study focuses on characterising the microbial diversity associated with T. favus. We have used denaturing gradient gel electrophoresis together with clonal and deep sequencing of microbial 16S rRNA gene amplicons to show that specimens of this sponge species contain a distinct and conserved microbial population, which is stable over time and is dominated by a unique Betaproteobacterium species. PMID- 22310803 TI - Bacterial and archaeal symbionts in the South China Sea sponge Phakellia fusca: community structure, relative abundance, and ammonia-oxidizing populations. AB - Many biologically active natural products have been isolated from Phakellia fusca, an indigenous sponge in the South China Sea; however, the microbial symbionts of Phakellia fusca remain unknown. The present investigations on sponge microbial community are mainly based on qualitative analysis, while quantitative analysis, e.g., relative abundance, is rarely carried out, and little is known about the roles of microbial symbionts. In this study, the community structure and relative abundance of bacteria, actinobacteria, and archaea associated with Phakellia fusca were revealed by 16S rRNA gene library-based sequencing and quantitative real time PCR (qRT-PCR). The ammonia-oxidizing populations were investigated based on amoA gene and anammox-specific 16S rRNA gene libraries. As a result, it was found that bacterial symbionts of sponge Phakellia fusca consist of Proteobacteria including Gamma-, Alpha-, and Delta-proteobacteria, Cyanobacteria with Gamma-proteobacteria as the predominant components. In particular, the diversity of actinobacterial symbionts in Phakellia fusca is high, which is composed of Corynebacterineae, Acidimicrobidae, Frankineae, Micrococcineae, and Streptosporangineae. All the observed archaea in sponge Phakellia fusca belong to Crenarchaeota, and the detected ammonia-oxidizing populations are ammonia-oxidizing archaea, suggesting the nitrification function of sponge archaeal symbionts. According to qRT-PCR analysis, bacterial symbionts dominated the microbial community, while archaea represented the second predominant symbionts, followed by actinobacteria. The revealed diverse prokaryotic symbionts of Phakellia fusca are valuable for the understanding and in-depth utilization of Phakellia fusca microbial symbionts. This study extends our knowledge of the community, especially the relative abundance of microbial symbionts in sponges. PMID- 22310804 TI - Algorithm for estimation of brain structural location from head surface shape in young children. AB - If the brain structural coordinates could be estimated using the individual head shape, magnetoencephalography and near-infrared spectroscopy would be more ideal brain functional imaging methods especially for young human children. First, we propose an algorithm to estimate brain coordinates with reference to the head surface shape in preschool children. Second, we examined its spatial error range using a leave-one-out procedure within 38 samples of child head and brain structures. The mean error of landmarks was 13.6+/-5.3 mm on the head surface and 18.5+/-12.4 mm in the intracranial structure between estimated and actual brain coordinates. PMID- 22310805 TI - Post-protein binding metal-mediated coupling of an acridine orange-based fluorophore. AB - The HEW lysozyme (Lys) and the fac-[Re(CO)(3)(H(2)O)(3)](+) complex (1) are used as a simple model system for the description of a new approach to the labelling polypeptides with fluorescent tags. The strategy takes advantage of the reaction of an acridine orange-based fluorophore (AO) with the non-native metal fragment 1 hybridized on the enzyme. A synthetic methodology for the quantitative metallation of the protein is first described and it is then shown that the exogenous metal complex can be exploited for the coupling of the fluorescent probe. All Lys-derived species were characterized by various spectroscopic techniques. It is shown that the approach does not significantly alter the activity of the final fluorescent metallo-protein conjugate (Lys2). The accumulation of Lys2 on Micrococcus lysodeikticus bacteria was observed via confocal laser scanning microscopy. PMID- 22310806 TI - Combined coagulation-disk filtration process as a pretreatment of ultrafiltration and reverse osmosis membrane for wastewater reclamation: an autopsy study of a pilot plant. AB - The effects of the combined coagulation-disk filtration (CC-DF) process on the fouling characteristics and behavior caused by interactions between effluent organic matter (EfOM) and the membrane surfaces of the ultrafiltration (UF) and reverse osmosis (RO) membranes in a pilot plant for municipal wastewater reclamation (MWR) were investigated. The feed water from secondary effluents was treated by the CC-DF process used as a pretreatment for the UF membrane to mitigate fouling formation and the permeate from the CC-DF process was further filtered by two UF membrane units in parallel arrangement and fed into four RO modules in a series connection. The CC-DF process was not sufficient to mitigate biofouling but the UF membrane was effective in mitigating biofouling on the RO membrane surfaces. Fouling of the UF and RO membranes was dominated by hydrophilic fractions of EfOM (e.g., polysaccharide-like and protein-like substances) and inorganic scaling (e.g., aluminum, calcium and silica). The desorbed UF membrane foulants included more aluminum species and hydrophobic fractions than the desorbed RO membrane foulants, which was presumably due to the residual coagulants and aluminum-humic substance complexes. The significant change in the surface chemistry of the RO membrane (a decrease in surface charge and an increase in contact angle of the fouled RO membranes) induced by the accumulation of hydrophilic EfOM onto the negatively charged RO membrane surface intensified the fouling formation of the fouled RO membrane by hydrophobic interaction between the humic substances of EfOM with relatively high hydrophobicity and the fouled RO membranes with decreased surface charge and increased contract angle. PMID- 22310807 TI - Surface functionalization of nanoparticles for nanomedicine. AB - Control of interactions between nanoparticles and biosystems is essential for the effective utilization of these materials in biomedicine. A wide variety of nanoparticle surface structures have been developed for imaging, sensing, and delivery applications. In this research Highlight, we will emphasize advances in tailoring nanoparticle interfaces for implementation in nanomedicine. PMID- 22310808 TI - First microwave-assisted synthesis of an electron-rich phosphane and its coordination chemistry with platinum(II) and palladium(II) AB - The P-O ligand 3-(di(2-methoxyphenyl)phosphanyl)propionic acid (HL) was synthesized by a microwave-assisted reaction of a secondary phosphane. The coordination of HL to Pt(II) yielded the neutral mononuclear complex trans [PtCl(kappa(2)-P,O-L)(kappa-P-HL)] (1), while the reaction of PdClMe(eta(4)-COD) (COD = 1,4-cyclooctadiene) with HL in the presence of NEt(3) gave the anionic Pd(II) compound of the formula (HNEt(3))[PdClMe(kappa(2)-P,O-L)] (2). Upon crystallization of the latter compound the neutral chloride-bridged dimetallic compound cis-[Pd(MU-Cl)Me(HL)](2) (3) was obtained. HL, 1 and 3.CH(2)Cl(2) have been characterized by single crystal X-ray structure analyses. PMID- 22310809 TI - The evolving Indian AIDS epidemic: hope & challenges of the fourth decade. PMID- 22310810 TI - 'Getting to zero': a steep path ahead. PMID- 22310811 TI - Genetic correlates influencing immunopathogenesis of HIV infection. AB - Variability to HIV infection, its progression as well as responsiveness to antiretroviral therapy (ART) is observed among individuals including viraemia controllers or exposed uninfected, rapid versus slow progressors and ART responders compared to non responders. This differential responsiveness/vulnerability to HIV-1 is governed by multiple host genetic factors that include HLA, cytokines, chemokines, their receptors and others. This review highlights the influence of these genetic factors on HIV/AIDS outcome; however, in India, the information in this area is very limited and most of these genetic studies have been conducted in Caucasian and South African populations. Considering the population-specific differences in the frequencies of protective or susceptibility favouring alleles and their influence on the disease outcome, it is of utmost importance to strengthen ongoing efforts towards defining largely unknown genetic propensity in Indian population, particularly by recruitment of large cohorts of well categorized exposed uninfected individuals, rapid, long term non progressors and elite viraemic controllers. Multi-parametric analysis of these potentially interactive immunogenetic variables in these cohorts may help to define potential targets for diagnostics and therapy in a population specific manner. PMID- 22310812 TI - Genetic architecture of HIV-1 genes circulating in north India & their functional implications. AB - This review presents data on genetic and functional analysis of some of the HIV-1 genes derived from HIV-1 infected individuals from north India (Delhi, Punjab and Chandigarh). We found evidence of novel B/C recombinants in HIV-1 LTR region showing relatedness to China/Myanmar with 3 copies of Nfkappab sites; B/C/D mosaic genomes for HIV-1 Vpr and novel B/C Tat. We reported appearance of a complex recombinant form CRF_02AG of HIV-1 envelope sequences which is predominantly found in Central/Western Africa. Also one Indian HIV-1 envelope subtype C sequence suggested exclusive CXCR4 co-receptor usage. This extensive recombination, which is observed in about 10 per cent HIV-1 infected individuals in the Vpr genes, resulted in remarkably altered functions when compared with prototype subtype B Vpr. The Vpu C was found to be more potent in causing apoptosis when compared with Vpu B when analyzed for subG1 DNA content. The functional implications of these changes as well as in other genes of HIV-1 are discussed in detail with possible implications for subtype-specific pathogenesis highlighted. PMID- 22310813 TI - HIV testing in developing countries: what is required? AB - HIV diagnostic and follow up testing are usually done in laboratory settings. However, in developing countries there is a need to decentralize testing as the majority of the population lives in rural settings. In developing countries stringent quality assurance (QA) practices, which include appropriate training, development of standard operating procedures, maintenance of operator proficiency, routine use of quality control (QC) specimens, standardized data management, equipment calibration and maintenance, and biohazard safety with proper disinfection/disposal procedures are not routinely followed to ensure reliability of results and a safe work environment. The introduction of point-of care testing technologies involving the use of non-laboratorians in routine testing has further increased the complexity of QA. Therefore, a careful approach towards improvement of laboratories that encourages best practices, coupled with incentives, and review of government policies in point-of-care testing is needed to improve quality of testing as decentralization takes place. Development of a functional laboratory tiered network that facilitates communication, referral, training and problem solving could further enhance confidence in laboratory testing. There is also a need for special considerations in implementing a step wise approach towards quality improvement, strengthening of the supply chain management, human capacity development, infrastructure upgrade, and strong public private partnerships to ensure long term sustainability of these efforts. PMID- 22310814 TI - Antiretroviral therapy in Indian setting: when & what to start with, when & what to switch to? AB - With the rapid scale-up of antiretroviral therapy, there is a dramatic decline in HIV related morbidity and mortality in both developed and developing countries. Several new safe antiretroviral, and newer class of drugs and monitoring assays are developed recently. As a result the treatment guideline for the management of HIV disease continue to change. This review focuses on evolving science on Indian policy--antiretroviral therapy initiation, which drugs to start with, when to change the initial regimen and what to change. PMID- 22310815 TI - Current practices in laboratory monitoring of HIV infection. AB - After a diagnosis of HIV infection is made, the patient needs to be monitored using both clinical assessment and laboratory markers. HIV/AIDS monitoring is essential in guiding when to recommend initiation of therapy. Clinical monitoring will include staging of the HIV/AIDS disease using either the presence or absence of HIV-related signs and symptoms using the WHO staging system. Various laboratory methods can be used to monitor the disease progression and to guide whether the patient will need antiretroviral therapy or not. Laboratory monitoring for patients who are not on drugs is done to provide information about the stage of illness; to enable the clinician to make decisions on treatment and to give information on prognosis of the patient. Patients on drugs are monitored to assess their response to treatment with antiretroviral drugs and to detect any possible toxicity and improvement associated with the antiretroviral drugs. PMID- 22310816 TI - Low-cost assays for monitoring HIV infected individuals in resource-limited settings. AB - Use of a combination of CD4 counts and HIV viral load testing in the management of antiretroviral therapy (ART) provides higher prognostic estimation of the risk of disease progression than does the use of either test alone. The standard methods to monitor HIV infection are flow cytometry based for CD4+ T cell count and molecular assays to quantify plasma viral load of HIV. Commercial assays have been routinely used in developed countries to monitor ART. However, these assays require expensive equipment and reagents, well trained operators, and established laboratory infrastructure. These requirements restrict their use in resource limited settings where people are most afflicted with the HIV-1 epidemic. With the advent of low-cost and/or low-tech alternatives, the possibility of implementing CD4 count and viral load testing in the management of ART in resource-limited settings is increasing. However, an appropriate validation should have been done before putting them to use for patient testing. PMID- 22310817 TI - Optimizing adherence to antiretroviral therapy. AB - HIV has now become a manageable chronic disease. However, the treatment outcomes may get hampered by suboptimal adherence to ART. Adherence optimization is a concrete reality in the wake of 'universal access' and it is imperative to learn lessons from various studies and programmes. This review examines current literature on ART scale up, treatment outcomes of the large scale programmes and the role of adherence therein. Social, behavioural, biological and programme related factors arise in the context of ART adherence optimization. While emphasis is laid on adherence, retention of patients under the care umbrella emerges as a major challenge. An in-depth understanding of patients' health seeking behaviour and health care delivery system may be useful in improving adherence and retention of patients in care continuum and programme. A theoretical framework to address the barriers and facilitators has been articulated to identify problematic areas in order to intervene with specific strategies. Empirically tested objective adherence measurement tools and approaches to assess adherence in clinical/ programme settings are required. Strengthening of ART programmes would include appropriate policies for manpower and task sharing, integrating traditional health sector, innovations in counselling and community support. Implications for the use of theoretical model to guide research, clinical practice, community involvement and policy as part of a human rights approach to HIV disease is suggested. PMID- 22310818 TI - Diagnosis & treatment of tuberculosis in HIV co-infected patients. AB - Human immunodeficiency virus (HIV) associated tuberculosis (TB) remains a major global public health challenge, with an estimated 1.4 million patients worldwide. Co-infection with HIV leads to challenges in both the diagnosis and treatment of tuberculosis. Further, there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDR-TB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. Because of the poor performance of sputum smear microscopy in HIV-infected patients, newer diagnostic tests are urgently required that are not only sensitive and specific but easy to use in remote and resource-constrained settings. The treatment of co-infected patients requires antituberculosis and antiretroviral drugs to be administered concomitantly; challenges include pill burden and patient compliance, drug interactions, overlapping toxic effects, and immune reconstitution inflammatory syndrome. Also important questions about the duration and schedule of anti-TB drug regimens and timing of antiretroviral therapy remain unanswered. From a programmatic point of view, screening of all HIV-infected persons for TB and vice-versa requires good co-ordination and communication between the TB and AIDS control programmes. Linkage of co-infected patients to antiretroviral treatment centres is critical if early mortality is to be prevented. We present here an overview of existing diagnostic strategies, new tests in the pipeline and recommendations for treatment of patients with HIV-TB dual infection. PMID- 22310819 TI - HIV & immune reconstitution inflammatory syndrome (IRIS). AB - Antiretroviral therapy (ART) initiation in HIV-infected patients leads to recovery of CD4+T cell numbers and restoration of protective immune responses against a wide variety of pathogens, resulting in reduction in the frequency of opportunistic infections and prolonged survival. However, in a subset of patients, dysregulated immune response after initiation of ART leads to the phenomenon of immune reconstitution inflammatory syndrome (IRIS). The hallmark of the syndrome is paradoxical worsening of an existing infection or disease process or appearance of a new infection/disease process soon after initiation of therapy. The overall incidence of IRIS is unknown, but is dependent on the population studied and the burden of underlying opportunistic infections. The immunopathogenesis of the syndrome is unclear and appears to be result of unbalanced reconstitution of effector and regulatory T-cells, leading to exuberant inflammatory response in patients receiving ART. Biomarkers, including interferon-gamma (INF-gamma), tumour necrosis factor-alpha (TNF-alpha), C reactive protein (CRP) and inter leukin (IL)-2, 6 and 7, are subject of intense investigation at present. The commonest forms of IRIS are associated with mycobacterial infections, fungi and herpes viruses. Majority of patients with IRIS have a self-limiting disease course. ART is usually continued and treatment for the associated condition optimized. The overall mortality associated with IRIS is low; however, patients with central nervous system involvement with raised intracranial pressures in cryptococcal and tubercular meningitis, and respiratory failure due to acute respiratory distress syndrome (ARDS) have poor prognosis and require aggressive management including corticosteroids. Paradigm shifts in management of HIV with earlier initiation of ART is expected to decrease the burden of IRIS in developed countries; however, with enhanced rollout of ART in recent years and the enormous burden of opportunistic infections in developing countries like India, IRIS is likely to remain an area of major concern. PMID- 22310820 TI - Parasitic infections in HIV infected individuals: diagnostic & therapeutic challenges. AB - After 30 years of the human immunodeficiency virus (HIV) epidemic, parasites have been one of the most common opportunistic infections (OIs) and one of the most frequent causes of morbidity and mortality associated with HIV-infected patients. Due to severe immunosuppression, enteric parasitic pathogens in general are emerging and are OIs capable of causing diarrhoeal disease associated with HIV. Of these, Cryptosporidium parvum and Isospora belli are the two most common intestinal protozoan parasites and pose a public health problem in acquired immunodeficiency syndrome (AIDS) patients. These are the only two enteric protozoan parasites that remain in the case definition of AIDS till today. Leishmaniasis, strongyloidiasis and toxoplasmosis are the three main opportunistic causes of systemic involvements reported in HIV-infected patients. Of these, toxoplasmosis is the most important parasitic infection associated with the central nervous system. Due to its complexity in nature, toxoplasmosis is the only parasitic disease capable of not only causing focal but also disseminated forms and it has been included in AIDS-defining illnesses (ADI) ever since. With the introduction of highly active anti-retroviral therapy (HAART), cryptosporidiosis, leishmaniasis, schistosomiasis, strongyloidiasis, and toxoplasmosis are among parasitic diseases reported in association with immune reconstitution inflammatory syndrome (IRIS). This review addresses various aspects of parasitic infections in term of clinical, diagnostic and therapeutic challenges associated with HIV-infection. PMID- 22310821 TI - Human immunodeficiency virus & cardiovascular risk. AB - Highly active antiretroviral therapy (HAART) significantly changed the prevalence of the cardiovascular manifestations of human immunodeficiency virus (HIV)/AIDS. In developed countries, a 30 per cent reduction in the prevalence of cardiomyopathy and pericardial effusion was observed, possibly related to a reduction of opportunistic infections and myocarditis. In developing countries, however, where the availability of HAART is limited, and the pathogenic impact of nutritional factors is significant, a 32 per cent increase was seen in the prevalence of cardiomyopathy and related high mortality rate from congestive heart failure. Also, some HAART regimens in developed countries, especially those including protease inhibitors, may cause, in a high proportion of HIV-infected patients, a lipodystrophy syndrome that is associated with an increased risk of cardiovascular events related to a process of accelerated atherosclerosis. Careful cardiac screening is warranted for patients who are being evaluated for, or who are receiving HAART regimens, particularly for those with known underlying cardiovascular risk factors, according to the most recent clinical guidelines. PMID- 22310822 TI - HIV serodiscordant relationships in India: translating science to practice. AB - Over the past 30 years, several interventions have been identified to prevent HIV transmission from HIV-infected persons to uninfected persons in discordant relationships. Yet, transmissions continue to occur. Interventions such as voluntary counselling and testing, condom promotion and risk reduction counselling are very effective in preventing transmission among serodiscordant couples but are underutilized in India despite their widespread availability. New interventions such as pre-risk exposure prophylaxis and universal antiretroviral therapy (irrespective of CD4 count) have been newly identified but face several challenges that impede their widespread implementation in India. Discordant couples in India also face certain unique socio-cultural issues such as marital and fertility pressure. We briefly review the various interventions (existing and novel) available for persons in discordant relationships in India and socio cultural issues faced by these individuals and make recommendations to maximize their implementation. PMID- 22310823 TI - Paediatric HIV--trends & challenges. AB - With the availability of antiretroviral therapy (ART), HIV infection, which was once considered a progressively fatal illness, has now become a chronic treatable condition in children, as in adults. However, the challenges these children are forced to face are far more daunting. The most significant shortcoming in the response to paediatric HIV remains the woefully inadequate prevention of mother to-child transmission (PMTCT), allowing a large number of children to be born with HIV in the first place, in spite of it being largely preventable. In the west, mother-to-child transmission has been virtually eliminated; however, in resource-limited settings where >95 per cent of all vertical transmissions take place, still an infected infants continue to be born. There are several barriers to efficient management: delayed infant diagnosis, lack of appropriate paediatric formulations, lack of skilled health personnel, etc. Poorly developed immunity allows greater dissemination throughout various organs. There is an increased frequency of malnutrition and infections that may be more persistent, severe and less responsive to treatment. In addition, these growing children are left with inescapable challenges of facing not only lifelong adherence with complex treatment regimens, but also enormous psychosocial, mental and neuro-cognitive issues. These unique challenges must be recognized and understood in order to provide appropriate holistic management enabling them to become productive citizens of tomorrow. To address these multi-factorial issues, there is an urgent need for a concerted, sustainable and multi-pronged national and global response. PMID- 22310824 TI - HIV in Indian MSM: reasons for a concentrated epidemic & strategies for prevention. AB - Men who have sex with men (MSM) in India are disproportionately likely to be HIV infected, and face distinct psychosocial challenges. Understanding the unique socio-cultural issues of MSM in India and how they relate to HIV risk could maximize the utility of future prevention efforts. This review discusses: (i) the importance of addressing co-occurring mental health issues, such as depression, which may interfere with MSM's ability to benefit from traditional risk reduction counselling, (ii) reducing HIV-related stigma among health providers, policymakers and the lay public, and (iii) the role for non-governmental organizations that work with the community to play in providing culturally relevant HIV prevention programmes for MSM. PMID- 22310825 TI - Microbicides for HIV prevention. AB - Although the HIV incidence rate has slowed in some countries, HIV remains a serious health challenge, particularly in the developing world. The epidemic is increasingly feminised, with young women at high risk of acquiring the virus. There is thus a clear requirement for acceptable woman-initiated methods of HIV prevention. Foremost among these are vaginally-applied substances known as microbicides; early research into potential microbicides focussed on non-HIV specific compounds such as surfactants and polyanionic entry inhibitors. However, proof of the microbicide concept as a viable prevention strategy was not provided until the CAPRISA 004 trial of a microbicide containing the HIV-specific antiretroviral tenofovir was completed in mid-2010. Confirmation of the proof of concept provided by CAPRISA 004 by at least two major trials will hopefully lead to licensure of the product by 2018. Parallel studies are planned to ascertain the feasibility of implementation of these products in the public sector with subsequent research focussed on appropriate and acceptable methods of delivery of the active ingredient, and to increase adherence through other delivery systems such as vaginal rings. PMID- 22310826 TI - Microbicides: a new hope for HIV prevention. AB - Human immunodeficiency virus (HIV), causative agent of acquired immunodeficiency syndrome (AIDS), is a global health concern. To control its transmission, safe sex has been proposed as one of the strategies. Microbicides- intravaginal/intrarectal topical formulations of anti-HIV agents have also been proposed to prevent HIV transmission. Microbicides would provide protection by directly inactivating HIV or preventing the attachment, entry or replication of HIV in susceptible target cells as well as their dissemination from target cells present in semen or the host cells lining the vaginal/rectal wall to other migratory cells. Microbicides must be safe, effective following vaginal or rectal administration, and should cause minimal or no genital symptoms or inflammations following long-term repeated usage. However, a safe and efficacious anti-HIV microbicide is not yet available despite the fact that more than 60 candidate agents have been identified to have in vitro activity against HIV, several of which have advanced to clinical testing. Nonetheless, proof-of-concept of microbicides has been established based on the results of recent CAPRISA 004 clinical trials. In this article, the trends and challenges in the development of effective and safe microbicides to combat HIV transmission are reviewed. PMID- 22310827 TI - Prevalence of HIV among blood donors in a tertiary care centre of north India. AB - BACKGROUND & OBJECTIVES: India has the second highest HIV population in the world with about 2.5-3.0 million cases. HIV-2 cases among general and blood donor population have also been reported mostly from west and south India. This single centre study was carried out to observe the HIV-1 and HIV-2 prevalence among blood donors from north India. METHODS: A total of 2,04,677 people were screened for the presence of HIV infection over the 11 year period (1999 to 2009). Till 2004, a third generation ELISA kit was used. From 2005 till January 2009 all tests were done using the fourth generation ELISA kit which detected the presence of HIV-1 P24 antigen and anti-HIV antibodies. From February 2009 onwards, the kits used were Genscreen ULTRA HIV Ag-Ab Assay. RESULTS: A total of 506 (0.247%) donors were found to be repeat reactive for HIV. Of these, 486 (96%) donors tested using the Western blot were found positive for HIV-1 infection. Twenty (4%) donors showed a negative Western blot result, none of the donors were found reactive for HIV-2 infection. INTERPRETATION & CONCLUSIONS: The prevalence of HIV was 0.249 per cent among blood donors of north India. No HIV-2 case was found among the studied blood donor population indicating that it is not a threat currently. PMID- 22310828 TI - Barriers to ART adherence & follow ups among patients attending ART centres in Maharashtra, India. AB - BACKGROUND & OBJECTIVES: Adherence to ART is a patient specific issue influenced by a variety of situations that a patient may encounter, especially in resource limited settings. A study was conducted to understand factors and influencers of adherence to ART and their follow ups among patients attending ART centres in Maharashtra, India. METHODS: Between January and March 2009, barriers to ART adherence among 32 patients at three selected ART centres functioning under national ART roll-out programme in Maharashtra, India, were studied using qualitative methods. Consenting patients were interviewed to assess barriers to ART adherence. Constant comparison method was used to identify grounded codes. RESULTS: Patients reported multiple barriers to ART adherence and follow up as (i) Financial barriers where the contributing factors were unemployment, economic dependency, and debt, (ii) social norm of attending family rituals, and fulfilling social obligations emerged as socio-cultural barriers, (iii) patients' belief, attitude and behaviour towards medication and self-perceived stigma were the reasons for sub-optimal adherence, and (iv) long waiting period, doctor patient relationship and less time devoted in counselling at the center contributed to missed visits. INTERPRETATION & CONCLUSIONS: Mainstreaming ART can facilitate access and address 'missed doses' due to travel and migration. A 'morning' and 'evening' ART centre/s hours may reduce work absenteeism and help in time management. Proactive 'adherence probing' and probing on internalized stigma might optimize adherence. Adherence probing to prevent transitioning to suboptimal adherence among patients stable on ART is recommended. PMID- 22310829 TI - Genital mycoplasma & Chlamydia trachomatis infections in treatment naive HIV-1 infected adults. AB - BACKGROUND & OBJECTIVES: Sexually transmitted infections (STIs) enhance the transmission of human immunodeficiency virus (HIV). Thus, screening for STIs is a routine component of primary HIV care. There are limited data for selective screening guidelines for genital mycoplasmas and Chlamydia trachomatis in HIV infected adults. The aim of the present study was to determine the frequency of genital infections with Ureaplasma spp., Mycoplasma hominis, M. genitalium and C. trachomatis in treatment naive asymptomatic HIV-1 - infected adults and study their association with CD4+ T-cell count. METHODS: First-void urine samples were collected from 100 treatment-naive HIV-1-infected adults and 50 healthy volunteers. C. trachomatis and M. genitalium were detected by polymerase chain reaction (PCR). Ureaplasma spp. and M. hominis were detected by both culture and PCR. Circulating CD4+ cell counts of HIV-1-infected patients were determined from peripheral blood by flow-cytometry. RESULTS: C. trachomatis was detected in 7 per cent of HIV-1-infected adults compared to none in control population. Ureaplasma spp. and M. hominis showed infection rates of 6 and 1 per cent in the HIV group and 2 and 0 per cent in the control group, respectively. None of the individuals from the patient and control groups was tested positive for M. genitalium. A significant association was found between CD4 cell count and detection of C. trachomatis in HIV-infected adults (P = 0.01). INTERPRETATION & CONCLUSIONS: Screening of HIV-infected individuals for C. trachomatis infection could be recommended as a routine component of HIV care. The role of mycoplasmas as co pathogens of the genitourinary tract in HIV-1 infected patients seems to be unlikely. Further longitudinal studies need to be done to confirm these findings. PMID- 22310830 TI - Dietary adequacy of HIV infected individuals in north India--a cross-sectional analysis. AB - BACKGROUND & OBJECTIVES: Dietary inadequacy is common in developing countries and so is in immune-deficient HIV infected individuals. Hence, an assessment of dietary patterns was done among a group of HIV infected individuals and compared with recommended dietary allowances. METHODS: One hundred consecutive HIV infected individuals were interviewed from the Immunodeficiency Clinic of a tertiary care center at Chandigarh. Dietary intake was assessed by 24 h recall method. Mean carbohydrate, protein and fat intakes were evaluated. Mean difference in the calorie intake from recommended dietary intake was then calculated. Mean absolute CD4 cell count was calculated and correlated with BMI and mean calorie intake. RESULTS: Mean weight and BMI of the individuals participated in the study was 58.6 +/- 11.7 (range, 34 - 94) kg and 21.5 +/- 3.7 (range, 13.6 - 36.7) kg/m [2] , respectively. Mean total calories intake was 1713 +/- 292.8 (860 - 2525) calories/day and mean difference in the calories taken from the standard values was 249.5 +/- 190.7 (10.6 - 967.5) calories/day. There was no significant correlation between CD4 cell count and total calories taken. INTERPRETATION & CONCLUSIONS: In HIV-infected individuals the energy intake was significantly lower than the recommended average intake. Hence, efforts should be taken to ensure that HIV-infected individuals have access to high-quality, nutritious food choices that promote optimal dietary patterns. PMID- 22310831 TI - Loss of CD127 & increased immunosenescence of T cell subsets in HIV infected individuals. AB - BACKGROUND & OBJECTIVES: HIV infection is characterized by a perturbation in T cell homeostasis, leading to alteration in T cell subsets. In addition to alteration in differentiation, HIV infection also leads to change in T cell survival and regenerative capacity, as suggested by differential expression of CD127 and CD57. We evaluated the expression patterns of CD127 and CD57 on CD4 and CD8 effector, memory and naive T cell subsets in HIV-infected and uninfected individuals. METHODS: We characterized T cell subsets based on expression of these markers, and compared their expression pattern in HIV infected subjects and uninfected controls. We further assessed therapy generated changes in these subsets and expression of CD127 and CD57 on them. RESULTS: There was a generalized decrease in naive CD4 and CD8 T cells in HIV infected subjects. These changes in T cell subset distribution were related to antigen load. CD127 expression was significantly reduced in T cells from HIV infected subject. In association to this, HIV infected subjects had higher percentage of T cell subsets expressing CD57. Increased CD57 and reduced CD127 expression correlated with plasma viraemia and CD8 T cell activation state. Incomplete restoration of T cell subset proportions was observed, despite suppression of viral replication and increase in CD4 T cell counts. Further, the improvement was more pronounced in CD127 expression. INTERPRETATION & CONCLUSIONS: HIV infected subjects have reduced T cell regenerative capacity along with increased senescence, highlighting decreased proliferation and effector activities. PMID- 22310832 TI - Performance of microscopy for detection of microsporidial spores from stool samples of HIV infected individuals with diarrhoea. PMID- 22310833 TI - Initial experience of the i-gel supraglottic airway by the residents in pediatric patients. AB - PURPOSE: Insertion of a laryngeal mask airway (LMA) is occasionally difficult in children because of their anatomical features and variations. A new single-use supraglottic airway device, the i-gel airway, was recently introduced. The objective of this study was to show the initial experience of the i-gel airway device by the residents for pediatric patients. METHODS: With approval from the local ethics committee and parental informed consent, 70 children undergoing minor surgery in the supine position, ASA score I-II, were investigated. Exclusion included patients having thoracic, neurosurgical, spine, and otolaryngological procedures. Patients were divided into three groups: group 1 was airway size 1.5 for patients weighing 5-12 kg, group 2 was size 2 for 10-25 kg, and group 3 was size 2.5 for those weighing 25-35 kg. The following seven characteristics were evaluated: (1) ease of the i-gel and gastric tube insertion; (2) leak pressure; (3) tidal volume/body weight at leak pressure point; (4) fiberscope score; (5) insertion time; (6) hypoxia rate (laryngospasm); and (7) coughing and trace of bleeding. RESULTS: The overall insertion success rate and the success rate at first attempt were 99% and 94%, respectively. Gastric tube insertions were easy in all patients. The overall leak pressure was 23 +/- 5 cmH(2)O. The tidal volume per body weight was 24 +/- 10 ml/kg. A good view of the fiberscope was achieved in 79%. In group 1 (size 1.5), one failed insertion, two dislocations, and one dysphonia were observed. Hypoxia rate was 1%. There was no case with coughing and trace of bleeding. CONCLUSION: These results show that the i-gel airway is a safe and effective device for use by residents who do not have experience with insertion of a pediatric LMA. However, using size 1.5, special caution should be taken to protect the infant airway, similar to what has been previously reported for other airway devices. PMID- 22310834 TI - Anesthetic management during tracheotomy in a child with respiratory distress caused by severe intubation-induced glottic stenosis. AB - We provided anesthetic management during a tracheotomy procedure for a child who demonstrated labored respiration during inspiration because of severe glottic stenosis and bilateral vocal cord paralysis caused by tracheal intubation. A 4 year-old boy developed acute respiratory depression associated with influenza pneumonia and had been under respiratory management with mechanical ventilation with tracheal intubation for 3 days. Following extubation, an upper-airway obstruction immediately appeared. The symptoms later worsened because of development of a common cold, and the patient underwent an emergency tracheotomy. For anesthetic management, we used a combination of ketamine with low concentration sevoflurane inhalation. The tracheotomy was performed safely without respiratory complications by employing manual-assisted ventilation, while spontaneous breathing was preserved by use of a face mask. PMID- 22310835 TI - Possible implication of Mdm2 as a prognostic marker in invasive laryngeal carcinoma. AB - Laryngeal squamous cell carcinoma is one of the most common malignant neoplasms of the head and neck. In Brazil, laryngeal tumors represent 2% of all cancers and are associated with approximately 3,000 deaths annually. Human papillomavirus (HPV) has been reported to play an important role in the etiology of laryngeal cancer. The aim of the present study was to evaluate the expression of p53, p27, and Mdm2 in laryngeal carcinomas. Sixty-three larynx biopsies were selected for the study, including 9 in situ laryngeal carcinomas, 27 laryngeal carcinomas without metastasis and 27 laryngeal carcinomas with metastasis. Twenty-seven cervical lymph nodes from patients with metastatic lesions were also evaluated. The expression levels of p53, p27, and Mdm2 were assessed by immunohistochemistry using a computer-assisted system. HPV detection and typing were performed using PCR, and the HPV types that were evaluated included HPV 6, 11, 16, 18, 31 and 33. Out of 63 patients, 53 (84.1%) were positive for beta-globin (internal control), and 10 (15.9%) were beta-globin negative and therefore excluded from the evaluation. Thus, 7 (13.2%) out of 53 patients were HPV positive, and 46 (86.8%) out of 53 patients were HPV negative. Statistically significant differences (p < 0.05) in Mdm2 expression levels were observed in the in situ laryngeal carcinoma samples compared with the laryngeal carcinoma samples with metastasis. No statistically significant differences (p > 0.05) in either p53 or p27 expression levels were detected. These findings suggest that Mdm2 may be associated with the invasiveness and aggressiveness of laryngeal carcinomas. PMID- 22310836 TI - Laryngotracheal stenosis and restenosis. What has the influence on the final outcome? AB - The aim of this study is to analyze the impact of various parameters on the course and treatment outcome in patients with laryngotracheal stenosis and recurrent stenosis. Two groups of patients were compared: Group I included 29 patients with primary stenosis, and Group II included 22 patients with recurrent stenosis. The most frequent etiological factor for the development of stenosis was prolonged endotracheal intubation (79.3:77.3%), with subglottic-tracheal (44.8:45.5%) and tracheal (48.3:36.4%) localization being the most affected. Subglottic-tracheal stenosis was more common in men. There were no significant differences between the groups in regard to the grade of lumen obstruction and the length of the resected segment. In male patients, the length of the resected stenotic segment was significantly longer. Subglottic-tracheal stenoses were longer than tracheal ones. Various surgical procedures were performed, with additional management of recurrent laryngeal nerve paralysis, if necessary. Laryngotracheal reconstruction (LTR) with costal cartilage grafting (CCG) was statistically significantly more often performed in Group II, while cricotracheal resection (CTR) was more common in Group I. The incidence of complications in Group I was 24.1%, and in Group II it was 31.8%. Satisfactory airway lumen with undisturbed breathing was achieved in 93.1% of patients in Group I, and in 95.3% in Group II. Since the success rate was similar in both groups of the patients, it could be concluded that treatment outcome depends less on the factors associated with the stenosis, and more on adequate choice of surgical procedure and surgical team know-how. PMID- 22310837 TI - Human mesenchymal stromal cells from adipose tissue of the neck. AB - Mesenchymal stromal cells (MSC) have been introduced into the field of tissue engineered airway transplantation. Since patients with extensive tracheal defects often require an open tracheotomy, this study investigated if MSC could be obtained from the adipose tissue of the neck during this procedure. Cells were isolated by plastic adherence from the adipose tissue of 8 patients. Cell isolates were analyzed for (i) proliferation, (ii) the expression of CD marker molecules and (iii) multilineage differentiation. The isolated spindle-shaped cells showed a high proliferation capacity and the flow cytometric analysis revealed a distinct population meeting the criteria for MSC. Using classical MSC cultivation protocols the characterized cells showed adipogenic, chondrogenic and osteogenic differentiation for all analyzed cell isolates. This study was able to demonstrate that sufficient amounts of stem/progenitor cells can be easily isolated from adipose tissue of the neck obtained during open tracheotomy. These cells may be a source for future tracheal replacement therapies. PMID- 22310838 TI - Early rehabilitation for unilateral peripheral vestibular disorders: a prospective, randomized investigation using computerized posturography. AB - Patients with unilateral vestibular lesions have a set of deficits requiring compensation based on the inherent plasticity of the central nervous system. In the 1940s, it was reported that patients with unilateral vestibular dysfunctions who exercised recovered faster than those who did not. The present prospective, randomized investigation aimed to assess the role of a computerized posturography assisted early vestibular rehabilitation protocol combined with a home-based exercise program in the treatment of patients with unilateral peripheral vestibular disorders occurring 2 weeks previously. Fifteen patients were randomly assigned to a 5-week posturography-assisted vestibular rehabilitation protocol and a home-based exercise program (Group A), while 15 simply awaited spontaneous compensation (Group B). All patients underwent computerized posturography approximately 2 weeks after their vestibular disorder was diagnosed and again after 6 weeks. Ten healthy volunteers were also studied (Group C). After rehabilitation, Group A patients improved significantly in most sensory measures [modified clinical test of sensory organization and balance (mCTSIB)] and motor parameters [limits of stability (LOS)] by comparison with preliminary outcomes, and there were no significant differences in sensory (mCTSIB) and motor (LOS) findings between Group A and the healthy volunteers. At the same time point, several motor (LOS) parameters were still altered in Group B by comparison with the healthy volunteers. These preliminary outcomes support the hypothesis that the compensation achievable after 6 weeks with a customized program of posturography-assisted vestibular rehabilitation and home-based exercises is superior to the results of physiological spontaneous compensation. PMID- 22310839 TI - Prospective evaluation of voice outcome during the first two years in male patients treated by radiotherapy or laser surgery for T1a glottic carcinoma. AB - In this prospective cohort study, we assessed voice outcome in patients before and up to 2 years after treatment for early glottic cancer either by radiotherapy or by laser surgery; 106 male patients, treated for T1aN0M0 glottic cancer either by endoscopic laser surgery (n = 67) or by radiotherapy (n = 39), participated in the study. Patients' voices were recorded and analysed pre-treatment and 3, 6, 12 and 24 months post-treatment at their routine visit at the outpatient clinic. Average fundamental frequency (F0), percent jitter, percent shimmer and normalized noise energy (NNE) were determined. After 2 years, local control rate was 95% in the radiotherapy group and 97% in the laser surgery group. Larynx preservation rate was 95% after radiotherapy and 100% after laser surgery. Voice outcome recovers more quickly in patients treated with laser surgery in comparison to radiotherapy: 3 months after laser surgery there is no longer a difference with regard to normal voices except for the fundamental frequency, which remains higher pitched, even in the longer term. For patients treated with radiotherapy it takes longer for jitter, shimmer and NNE to become normal, where jitter remains significantly different from normal voices even after 2 years. According to these results, we believe that laser surgery is the first treatment of choice in the treatment of selected cases of T1a glottic carcinomas with good functional and oncological results. PMID- 22310840 TI - Obstructive sleep apnea is underrecognized and underdiagnosed in patients undergoing bariatric surgery. AB - The aim of this study was to evaluate prevalence of obstructive sleep apnea among patients undergoing bariatric surgery and the predictive value of various clinical parameters: body mass index (BMI), neck circumference (NC) and the Epworth Sleepiness Scale (ESS). We performed a prospective, multidisciplinary, single-center observational study including all patients on the waiting list for bariatric surgery between June 2009 and June 2010, irrespective of history or clinical findings. Patients visited our ENT outpatient clinic for patient history, ENT and general examination and underwent a full night polysomnography, unless performed previously. As much as 69.9% of the patients fulfilled the criteria for OSA (mean BMI 44.2 +/- SD 6.4 kg/m(2)); 40.4% of the patients met the criteria for severe OSA. The regression models found BMI to be the best clinical predictor, while the ROC curve found the NC to be the most accurate predictor of the presence of OSA. The discrepancy of the results and the poor statistical power suggest that all three clinical parameters are inadequate predictors of OSA. In conclusion, in this large patient series, 69.9% of patients undergoing BS meet the criteria for OSA. More than 40% of these patients have severe OSA. A mere 13.3% of the patients were diagnosed with OSA before being placed on the waiting list for BS. On statistical analysis, increased neck circumference, BMI and the ESS were found to be insufficient predictors of the presence of OSA. Polysomnography is an essential component of the preoperative workup of patients undergoing BS. When OSA is found, specific perioperative measures are indicated. PMID- 22310841 TI - Chemical composition and in vitro cytotoxic, genotoxic effects of essential oil from Urtica dioica L. AB - The aim of this study was to determine the chemical composition of Urtica dioica essential oil, and to evaluate its cytotoxic and genotoxic effects, using cytogenetic tests such as the cytokinesis-block micronucleus assay and chromosomal aberration analysis in human lymphocyte cultures in vitro. GC-MS analysis of U. dioica essential oil identified 43 compounds, representing 95.8% of the oil. GC and GC-MS analysis of the essential oil of U. dioica revealed that carvacrol (38.2%), carvone (9.0%), naphthalene (8.9%), (E)-anethol (4.7%), hexahydrofarnesyl acetone (3.0%), (E)-geranyl acetone (2.9%), (E)-beta-ionone (2.8%) and phytol (2.7%) are the main components, comprising 72.2% of the oil. A significant correlation was found between the concentration of essential oil and the following: chromosomal aberrations, micronuclei frequency, apoptotic cells, necrotic cells, and binucleated cells. PMID- 22310842 TI - Microbial biomass and carbon mineralization in agricultural soils as affected by pesticide addition. AB - A laboratory study was conducted with four pesticides, viz. a fungicide (carbendazim), two insecticides (chlorpyrifos and cartap hydrochloride) and an herbicide (pretilachlor) applied to a sandy clay loam soil at a field rate to determine their effect on microbial biomass carbon (MBC) and carbon mineralization (C(min)). The MBC content of soil increased with time up to 30 days in cartap hydrochloride as well as chlorpyrifos treated soil. Thereafter, it decreased and reached close to the initial level by 90th day. However, in carbendazim treated soil, the MBC showed a decreasing trend up to 45 days and subsequently increased up to 90 days. In pretilachlor treated soil, MBC increased through the first 15 days, and thereafter decreased to the initial level. Application of carbendazim, chlorpyrifos and cartap hydrochloride decreased C(min) for the first 30 days and then increased afterwards, while pretilachlor treated soil showed an increasing trend. PMID- 22310843 TI - Extraction, cleanup, and chromatographic determination of imidacloprid residues in wheat. AB - This study presents an improved method for quantitative analysis of imidacloprid residues in wheat grain using high performance liquid chromatography. The study used chromatographic response (in terms of peak height) as a quantitative tool for determination instead of peak area. The peak height of imidacloprid showed a very good linear correlation (R(2) = 0.999) when compared with absolute values at six different concentrations. The limit of detection was found to be 0.01 MUg/mL. The recovery of imidacloprid residues in spiked wheat grain at three levels (0.03, 0.05, and 0.1 MUg/g) was in the range of 79%-88% with %RSD 5.72 at 0.05 MUg/g (w/w) and between 87% and 93% with %RSD 3.55 at 0.1 MUg/g (w/w). At 0.03 MUg/g (w/w) level, recovery was not within the recommended range of 70%-110%. Therefore, the lowest limit of quantification for this method was found to be 0.05 MUg/g. PMID- 22310844 TI - Observations of fallout from the Fukushima reactor accident in Cienfuegos, Cuba. AB - Following the recent accident at the Fukushima Daiichi nuclear power plant in Japan, radioactive contamination was observed near the reactor site. As a contribution towards the understanding of the worldwide impact of the accident, we collected fallout samples in Cienfuegos, Cuba, and examined them for the presence of above normal amounts of radioactivity. Gamma ray spectra measured from these samples showed clear evidence of fission products (131)I and (137)Cs. However, the fallout levels measured for these isotopes (135 +/- 4.78 mBq m(-2) day(-1) for (131)I and 10.7 +/- 0.38 mBq m(-2) day(-1)for (137)Cs) were very low and posed no health risk to the public. The doses received as consequence to the Fukushima fallout by the Cienfuegos population's (0.002 mSv per year) don't overcome the limit of dose (1 mSv per year) fixed for the public in Cuba. PMID- 22310845 TI - Metals in fish along the southeast coast of India. AB - Metal concentrations (cadmium, chromium, iron, lead, copper, manganese, zinc and mercury) in the muscle of five fish species (Epinephelus chlorostigma, Lutjanus russelli, Terapon jarbua, Cynoglossus arel and Lagocephalus lunaris) from the six fish landing centres along southeast coast of India were measured. In Cuddalore and Mudasalodai, the level of toxic metals cadmium, chromium and manganese were well above the permissible limits. Concentrations of cadmium, chromium, manganese and mercury in C. arel were above the permissible limit and it is consistent with their habitat and diet. The results showed a relationship between metal concentrations and pollution status of the areas. PMID- 22310846 TI - Phytotoxicity of thiocyanate to rice seedlings. AB - The acute toxicity of potassium thiocyanate (KSCN) and ammonium thiocyanate (NH(4)SCN) to rice seedlings was tested. Hydroponically-grown plants showed different responses to the two species of thiocyanate. NH(4)SCN caused more severe stress to rice seedlings than KSCN. A significant reduction in transpiration and relative growth was observed with all NH(4)SCN treatments (p < 0.01), while the effect of KSCN on rice seedlings was more evident at greater than 100 mg SCN/L (p < 0.01). Both chemicals had a negligible effect on total chlorophyll content in shoots of rice seedlings (p > 0.05). Although phyto transport of thiocyanate was apparent, rice seedlings showed significantly higher removal potential for NH(4)SCN than KSCN. PMID- 22310847 TI - Oxidative stress responses and recovery patterns in the liver of Oreochromis niloticus exposed to chlorpyrifos-ethyl. AB - Chlorpyrifos is the most common insecticide in freshwater ecosystems, and detected in agricultural and fishery product. In this study, Oreochromis niloticus were exposed to 5, 10 and 15 ppb sublethal concentrations of chlorpyrifos in order to determine the oxidative stress response in liver. Acetylcholinesterase (AChE) activity was significantly inhibited. Superoxide dismutase activity (SOD) increased after 15 days of chlorpyrifos treatments at all concentrations (146.95%, 53.04%, 208.70%, respectively). Malondialdehyde levels were higher than that of the control level after 15 days of 5 ppb (95.65%), 10 ppb (69.56%) and 15 ppb (252.17%) chlorpyrifos treatments. Malondialdehyde levels were also increased ranging from 59.09%, 113.63% to 195.46% after 30 days of 5, 10 and 15 ppb chlorpyrifos exposures. Glutathione S transferase activity decreased except for 15 days low concentration exposure. Catalase (CAT) activity decreased while there is no significant alteration in glutathione peroxidase activity. After recovery period, the low concentration group of chlorpyrifos provided a protection in AChE activity during recovery, but fish were observed to be unable to overcome the inhibition of AChE activity at high concentration groups. CAT activity remained reduced, SOD activity increased whereas the other biochemical parameters recovered to control levels. Results of this study suggest that chlorpyrifos induces oxidative stress in the liver of O. niloticus and this effect is not related with anti-acetylcholinesterase activity of pesticide. PMID- 22310848 TI - Pharmacotherapy: statins and new-onset diabetes mellitus--a matter for debate. PMID- 22310849 TI - SGLT2 inhibition in diabetes mellitus: rationale and clinical prospects. AB - This Review covers the rationale, physiological consequences and clinical application of pharmacological sodium-glucose cotransporter 2 (SGLT2) inhibition. In patients with type 2 diabetes mellitus, in whom renal glucose reabsorption might be upregulated, orally active, selective SGLT2 inhibitors improve glycaemic control to a therapeutically useful extent. Chronic administration of several SGLT2 inhibitors dose-dependently lowers HbA(1c) levels by 0.5-1.5% without causing hypoglycaemia. The unique mechanism of action of SGLT2 inhibitors-which does not hinge upon beta-cell function or tissue insulin sensitivity-means that they can exert their antihyperglycaemic effects in combination with any other oral antidiabetic drug as well as insulin. Available phase III studies confirm a good tolerability profile. Weight loss owing to urinary calorie leakage may be less than expected, but the negative energy balance offers a valuable clinical benefit. Offloading of sodium can assist blood pressure control. The progressive loss of efficacy in patients with reduced glomerular function will have to be balanced against the possibility of renal protection. The safety issues of genitourinary infections and cancer risk requires careful, proactive monitoring and analysis of robust exposure data, particularly in elderly, frail patients and in patients with impaired kidney function and/or high cardiovascular/cancer risk, who represent an increasing fraction of the population with diabetes mellitus. PMID- 22310850 TI - Bone: Osteoporosis screening intervals. PMID- 22310851 TI - Intensive insulin therapy in the ICU--reconciling the evidence. AB - Hyperglycaemia during critical illness unequivocally correlates with adverse outcome. Three proof-of-concept randomized controlled trials have shown that preventing hyperglycaemia in patients admitted to the intensive care unit (ICU) reduces organ failure and mortality. A subsequent multicentre, randomized controlled trial found that targeting normoglycaemia in this patient population does not affect organ function differently than targeting an intermediate glucose level (7.8-10.0 mmol/l). However, an intermediate glucose target evoked less hypoglycaemia and, for currently unexplained reasons, also fewer deaths than a normoglycaemic target. Moreover, tolerating a caloric deficit, rather than providing nutrients parenterally, accelerated recovery from critical illness in the presence of normoglycaemia. Whether macronutrient restriction renders moderate hyperglycaemia less harmful remains to be investigated. Hence, if adequate monitoring tools and expertise are available, normoglycaemia remains the only proven effective target for insulin treatment of hyperglycaemia in ICU patients. However, if these conditions are not fulfilled in clinical practice, is an intermediate target range preferable? In the absence of hard evidence, common sense supports such an intermediate blood glucose target. PMID- 22310852 TI - Obesity: Is prevalence leveling off? PMID- 22310853 TI - Musculoskeletal fracture: what is different in children?-skimboarding, fall, right foot pain. PMID- 22310854 TI - [68Ga]Gallium-labelled PSMA ligand as superior PET tracer for the diagnosis of prostate cancer: comparison with 18F-FECH. PMID- 22310855 TI - Adverse events in nuclear medicine - cause for concern? PMID- 22310856 TI - Surface modification of anatase nanoparticles with fused ring catecholate type ligands: a combined DFT and experimental study of optical properties. AB - Surface modification of nanocrystalline TiO(2) particles (45 A) with catecholate type ligands consisting of an extended aromatic ring system, i.e., 2,3 dihydroxynaphthalene and anthrarobin, was found to alter the optical properties of the nanoparticles in a similar way to modification with catechol. The formation of inner-sphere charge-transfer (CT) complexes results in a red shift of the semiconductor absorption compared to unmodified nanocrystallites and the reduction of the band gap upon the increase of the electron delocalization on the inclusion of additional rings. The binding structures were investigated by FTIR spectroscopy. The investigated ligands have the optimal geometry for binding to surface Ti atoms, resulting in ring coordination complexes of catecholate type (binuclear bidentate binding-bridging) thus restoring the six-coordinated octahedral geometry of surface Ti atoms. From the Benesi-Hildebrand plot, stability constants in methanol/water = 90/10 solutions at pH 2 of the order 10(3) M(-1) have been determined. Quantum chemical calculations on model systems using density functional theory (DFT) were performed to obtain vibrational frequencies of charge transfer complexes, and the calculated values were compared with the experimental data. PMID- 22310857 TI - Predictors of maternal identity of Korean primiparas. AB - PURPOSE: The purpose of this study was to identify factors influencing maternal identity of Korean primiparas. METHODS: The data were collected by a self-report questionnaire in 2006. The participants were 210 healthy primiparous women who delivered at one of three medical centers and revisited the outpatient department for follow up between 4 to 6 weeks after childbirth. Data were analyzed using the SPSS WIN 17.0 program with descriptive statistics, t-test, one way ANOVA, Pearson correlation coefficient, and stepwise multiple regression. RESULTS: Maternal identity was significantly correlated with Taekyo accomplishment, the culturally based prenatal preparation (p<.001). Transitional gratification to motherhood (p<.001), postpartum depression (p<.001), childcare stress (p<.001), infant temperament (p<.001), and social support (p<.001) were also significantly correlated with maternal identity. The stepwise multiple regression analysis showed that maternal identity was significantly predicted by transitional gratification to motherhood, infant temperament, childcare stress, and Taekyo accomplishment. These variables explained 31.0% of the variance of maternal identity. CONCLUSION: The results of this study suggest that postpartum nursing interventions to promote maternal identity should focus on reinforcing education and support for reducing childcare stress and infant difficulty, and increasing transitional gratification to motherhood. Also, prenatal encouragement and education for improving Taekyo accomplishment may be helpful to promote maternal identity after birth. PMID- 22310858 TI - Public knowledge and attitudes regarding antibiotic use in South Korea. AB - PURPOSE: This study was conducted to examine public level of knowledge and attitudes regarding antibiotic use and potential drug resistance. METHODS: A cross-sectional face-to-face survey of 1,177 residents aged 18 or over was conducted in Korea. A quota sampling method was used. RESULTS: Most respondents (70%) did not know that antibiotics are ineffective in treating coughs and colds. Two-thirds of the respondents were unaware of the conditions under which antibiotic resistance occurs, despite understanding the concept of resistance. Lower education level and older age were independently associated with inadequate knowledge. Lower education level, older age, inadequate knowledge and no exposure to the education campaign were independently associated with poor attitude. CONCLUSION: The results of this study demonstrate that the general public has misunderstandings and a lack of knowledge with regard to antibiotic use, despite a national educational campaign. However, the campaign may have had an effect on the public's attitudes towards antibiotics. PMID- 22310859 TI - Comparison of benefit estimation models in cost-benefit analysis: a case of chronic hypertension management programs. AB - PURPOSE: Cost-benefit analysis is one of the most commonly used economic evaluation methods, which helps to inform the economic value of a program to decision makers. However, the selection of a correct benefit estimation method remains critical for accurate cost-benefit analysis. This paper compared benefit estimations among three different benefit estimation models. METHODS: Data from community-based chronic hypertension management programs in a city in South Korea were used. Three different benefit estimation methods were compared. The first was a standard deterministic estimation model; second, a repeated-measures deterministic estimation model; and third, a transitional probability estimation model. RESULTS: The estimated net benefit of the three different methods were $1,273.01, $-3,749.42, and $-5,122.55 respectively. CONCLUSION: The transitional probability estimation model showed the most correct and realistic benefit estimation, as it traced possible paths of changing status between time points and it accounted for both positive and negative benefits. PMID- 22310860 TI - Usefulness of estimated height loss for detection of osteoporosis in women. AB - PURPOSE: This study was done to examine the threshold value of estimated height loss at which the risk of osteoporosis increases and to verify its discriminative ability in the detection of osteoporosis. METHODS: It was conducted based on epidemiological descriptive methods on 732 Korean women at a public healthcare center in Seoul between July and November 2010. ANOVA, Pearson correlation, logistic regression analysis and receiver operating characteristics (ROC) curve were used for data analysis. RESULTS: There was an age-related correlation between bone mineral density (lumbar spine: F=37.88, p<.001; femur: F=54.27, p<.001) and estimated height loss (F=27.68, p<.001). Estimated height loss increased significantly with decreasing bone mineral density (lumbar spine: r= .23, p<.001; femur: r=-.34, p<.001). The odds ratio for the point at which the estimated height loss affects the occurrence of osteoporosis was found to increase at a cut-off value of 2 cm and the area under ROC curve was .71 and .82 in lumbar spine and femur, respectively. CONCLUSION: The optimal cut-off value of the estimated height loss for detection of osteoporosis was 2 cm. Height loss is therefore a useful indicator for the self-assessment and prognosis of osteoporosis. PMID- 22310861 TI - Adaptation of evidence-based surgical wound care algorithm. AB - PURPOSE: This study was designed to adapt a surgical wound care algorithm that is used to provide evidence-based surgical wound care in a critical care unit. METHODS: This study used, the 'ADAPTE process', an international clinical practice guideline development method. The 'Bonnie Sue wound care algorithm' was used as a draft for the new algorithm. A content validity index (CVI) targeting 135 critical care nurses was conducted. A 5-point Likert scale was applied to the CVI test using a statistical criterion of .75. RESULTS: A surgical wound care algorithm comprised 9 components: wound assessment, infection control, necrotic tissue management, wound classification by exudates and depths, dressing selection, consideration of systemic factors, wound expected outcome, reevaluate non-healing wounds, and special treatment for non-healing wounds. All of the CVI tests were >=.75. Compared to existing wound care guidelines, the new wound care algorithm provides precise wound assessment, reliabilities of wound care, expands applicability of wound care to critically ill patients, and provides evidence and strength of recommendations. CONCLUSION: The new surgical wound care algorithm will contribute to the advancement of evidence-based nursing care, and its use is expected as a nursing intervention in critical care. PMID- 22310862 TI - Factors impacting the physical function of older adults in Korean long-term care hospitals. AB - PURPOSE: This study was conducted to examine activities of daily living (ADL) of older adults admitted to Korean long-term care hospitals (LTCHs), and to explore the patient and organizational factors that have an impact on the ADL of this population. METHODS: A secondary analysis of the Korean minimum data set (K-MDS) of patients (N=14,369) and of the profiles of LTCHs (N=358) from the Health Insurance Review and Assessment Service was done between January and July 2008. The outcome variable was ADL score 6 months after baseline assessment. Multi level linear regression was employed to explore the patient and organizational factors that affected ADL scores. RESULTS: Of the patients, 45.4% had a baseline ADL score of between 31 and 40, with a score of 40 indicating that the patient was entirely dependent for all items. None of the organizational characteristics were significantly associated with effects on the ADLs of older adults who had been in a LTHC for at least 6 months. However, patient characteristics, such as age, baseline ADL, frequency of physical therapy, urinary incontinence, fecal incontinence, pressure ulcers, and having a tube or catheter, were significantly associated with ADL 6 months after baseline. CONCLUSION: In order to maintain and improve the ADL of older adults in LTCHs, we should develop strategies to prevent urinary and fecal incontinence, pressure ulcers, unnecessary tubes or catheters, providing adequate physical therapy. Additional studies should include more detailed information regarding nursing staff, including RN hours for direct care, education level and turnover. PMID- 22310863 TI - Heart rate variability and metabolic syndrome in hospitalized patients with schizophrenia. AB - PURPOSE: Reduced heart rate variability significantly increases cardiovascular mortality. Metabolic syndrome increases the cardiac autonomic dysfunction. Recently, increasing cardiovascular mortality has been reported in patients with schizophrenia. This study was done to compare heart rate variability between adults with and without schizophrenia and to compare the relationship of heart rate variability to metabolic syndrome in hospitalized patients with schizophrenia. METHODS: This was a descriptive and correlational study in which 719 adults without schizophrenia and 308 adults with schizophrenia took part between May and June 2008. We measured the following: five-minute heart rate variability; high-frequency, low-frequency, the ratio of low-frequency to high frequency, and the Standard Deviation of all the normal RR intervals. Data was also collected on metabolic syndrome, abdominal obesity, triglycerides, HDL cholesterol, blood pressure and fasting glucose. RESULTS: The Standard Deviation of all the normal RR intervals values of heart rate variability indices were 1.53+/-0.18. The low-frequency and high-frequency values of heart rate variability indices were significantly higher in hospitalized patients with schizophrenia (3.89+/-1.36; 3.80+/-1.20) than those in the healthy participants (2.20+/-0.46; 2.10+/-0.46). There were no significant differences between the schizophrenic patients with and without metabolic syndrome. CONCLUSION: The results of this study indicate that schizophrenia patients have significantly lower cardiac autonomic control, but they have significantly higher low-frequency and high-frequency values than those of healthy adults. Use of antipsychotic drug may affect the autonomic nervous system in schizophrenic patients. Metabolic syndrome was not associated with cardiac autonomic control in schizophrenia patients. PMID- 22310864 TI - Effects of interactive pictorial education on community dwelling older adult's self efficacy and knowledge for safe medication. AB - PURPOSE: The purpose of this study was to examine the effects of interactive pictorial education on community dwelling older Korean adults' self-efficacy and knowledge for safe medication. METHODS: A quasi-experimental, three-group pre- and post-intervention design was used in this study. The interactive pictorial education was designed to suit the learning patterns and psychomotor skills of older adults. The education content, dealing with safe medication, was delivered over three sessions. A total of 136 older adults from local senior centers were assigned to one of the three groups: a) interactive pictorial education plus information booklet (experimental); b) education only with information booklet (conventional); or c) no intervention (control). RESULTS: Participants receiving interactive pictorial education had significantly higher self-efficacy (F=24.32, p<.001) and knowledge (F=24.26, p<.001) scores than the information booklet or control group at post intervention. Post-hoc analyses indicated that both the interactive pictorial and the information booklet groups had significantly higher self-efficacy and knowledge scores than the control group at the post-test point (p<.05). Furthermore, the interactive pictorial group had higher self-efficacy and knowledge scores than the information booklet group at the post-test point (p<.05). CONCLUSION: These results suggest that the interactive pictorial education is an innovative approach that provides a means for older adults to learn appropriate medication use to improve their own health. It empowers older adults with different literacy levels to enhance their self-efficacy and knowledge for the safe use of medication. PMID- 22310865 TI - Effectiveness of an interpersonal relationship program on interpersonal relationships, self-esteem, and depression in nursing students. AB - PURPOSE: The purpose of this study was to examine the effectiveness of an interpersonal relationship program on interpersonal relationships, self-esteem, and depression in nursing students. METHODS: This was a quasi-experiment with a nonequivalent control group pre-posttest design. Sixty-four nursing students participated in the study with 31 in the experimental group and 33 in the control group. They were from 3 different colleges of nursing located in Seoul. The interpersonal relationship program was held 10 times over 10 weeks, taking 90 minutes per session. The interpersonal relationship change scale developed by Schlein and Guemey, Rosenberg's self-esteem scale, and CED-S for depression were the instruments used in the study. The data collection period was from January 4 to March 8, 2011, and the collected data were analyzed with SPSS 14.0 using the Chi(2)-test, t-test, and paired t-test. RESULTS: The results showed a significant difference between the experimental group and the control group in terms of the degree of interpersonal relationships, self-esteem, and depression. CONCLUSION: The results indicate that interpersonal relationship programs have positive effects for improving interpersonal relationships and self-esteem, and decreasing depression in nursing students. PMID- 22310866 TI - Comparison of standardized peristomal skin care and crusting technique in prevention of peristomal skin problems in ostomy patients. AB - PURPOSE: This study was performed to compare the effects of standardized peristomal skin care (SPSC) and crusting technique (CT) on the peristomal skin of ostomates. SPSC was developed by a consensus among the expert group based on a comprehensive review of the relevant literature and hospital protocols. METHODS: A randomized controlled pilot trial with 2 parallel arms was used. A total of 81 ostomates, who were recruited from a tertiary hospital, completed the baseline, 1 month, 2-month, and 3-month follow-up (SPSC group, n=45; CT group, n=36). SPSC consisted of water cleansing and direct application of ostomy appliances. CT involved crusting hydrocolloid powder and patting with water sponge or protective barrier liquid film. The outcomes of the study were assessed by skin problems, such as discoloration, erosion and tissue overgrowth; the domains of the evaluation tool used in examining the peristomal skin. A generalized estimating equation model was used to examine the effects according to time and group. RESULTS: In both SPSC and CT groups, the likelihood of occurrence of discoloration (OR, 1.99; 95% CI, 1.61-2.46), erosion (OR, 1.87; 95% CI, 1.55 2.25) and tissue enlargement (OR, 1.94; 95% CI, 1.36-2.77) increased with time. There was no significant difference in discoloration between the groups, whereas the probability of erosion (OR, 0.38; 95% CI, 0.16-0.89) and tissue overgrowth (OR, 0.09; 95% CI, 0.02-0.55) was lower in the SPSC group than in CT group. CONCLUSION: SPSC was sufficient in preventing peristomal skin problems of ostomates compared to the CT. PMID- 22310867 TI - Effects of foot reflexology on fatigue, sleep and pain: a systematic review and meta-analysis. AB - PURPOSE: The purpose of this study was to evaluate the effectiveness of foot reflexology on fatigue, sleep and pain. METHODS: A systematic review and meta analysis were conducted. Electronic database and manual searches were conducted on all published studies reporting the effects of foot reflexology on fatigue, sleep, and pain. Forty four studies were eligible including 15 studies associated with fatigue, 18 with sleep, and 11 with pain. The effects of foot reflexology were analyzed using Comprehensive Meta-Analysis Version 2.0. The homogeneity and the fail-safe N were calculated. Moreover, a funnel plot was used to assess publication bias. RESULTS: The effects on fatigue, sleep, and pain were not homogeneous and ranged from 0.63 to 5.29, 0.01 to 3.22, and 0.43 to 2.67, respectively. The weighted averages for fatigue, sleep, and pain were 1.43, 1.19, and 1.35, respectively. No publication bias was detected as evaluated by fail safe N. Foot reflexology had a larger effect on fatigue and sleep and a smaller effect on pain. CONCLUSION: This meta-analysis indicates that foot reflexology is a useful nursing intervention to relieve fatigue and to promote sleep. Further studies are needed to evaluate the effects of foot reflexology on outcome variables other than fatigue, sleep and pain. PMID- 22310868 TI - Effect of DHEA on recovery of muscle atrophy induced by Parkinson's disease. AB - PURPOSE: The purpose of this study was to determine the effect of dehydroepiandrosterone (DHEA) on recovery of muscle atrophy induced by Parkinson's disease. METHODS: The rat model was established by direct injection of 6-hydroxydopamine (6-OHDA, 20MUg) into the left striatum using stereotaxic surgery. Rats were divided into two groups; the Parkinson's disease group with vehicle treatment (Vehicle; n=12) or DHEA treatment group (DHEA; n=22). DHEA or vehicle was administrated intraperitoneally daily at a dose of 0.34 mmol/kg for 21 days. At 22-days after DHEA treatment, soleus, plantaris, and striatum were dissected. RESULTS: The DHEA group showed significant increase (p<.01) in the number of tyrosine hydroxylase (TH) positive neurons in the lesioned side substantia nigra compared to the vehicle group. Weights and Type I fiber cross sectional areas of the contralateral soleus of the DHEA group were significantly greater than those of the vehicle group (p=.02, p=.00). Moreover, extracellular signal-regulated kinase (ERK) phosphorylation significantly decreased in the lesioned striatum, but was recovered with DHEA and also in the contralateral soleus muscle, Akt and ERK phosphorylation recovered significantly and the expression level of myosin heavy chain also recovered by DHEA treatment. CONCLUSION: Our results suggest that DHEA treatment recovers Parkinson's disease induced contralateral soleus muscle atrophy through Akt and ERK phosphorylation. PMID- 22310869 TI - Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems. AB - PURPOSE: Acute gastrointestinal (GI) dysfunction and failure have been increasingly recognized in critically ill patients. The variety of definitions proposed in the past has led to confusion and difficulty in comparing one study to another. An international working group convened to standardize the definitions for acute GI failure and GI symptoms and to review the therapeutic options. METHODS: The Working Group on Abdominal Problems (WGAP) of the European Society of Intensive Care Medicine (ESICM) developed the definitions for GI dysfunction in intensive care patients on the basis of the available evidence and current understanding of the pathophysiology. RESULTS: Definitions for acute gastrointestinal injury (AGI) with its four grades of severity, as well as for feeding intolerance syndrome and GI symptoms (e.g. vomiting, diarrhoea, paralysis, high gastric residual volumes) are proposed. AGI is a malfunctioning of the GI tract in intensive care patients due to their acute illness. AGI grade I = increased risk of developing GI dysfunction or failure (a self-limiting condition); AGI grade II = GI dysfunction (a condition that requires interventions); AGI grade III = GI failure (GI function cannot be restored with interventions); AGI grade IV = dramatically manifesting GI failure (a condition that is immediately life-threatening). Current evidence and expert opinions regarding treatment of acute GI dysfunction are provided. CONCLUSIONS: State-of the-art definitions for GI dysfunction with gradation as well as management recommendations are proposed on the basis of current medical evidence and expert opinion. The WGAP recommends using these definitions for clinical and research purposes. PMID- 22310870 TI - Bedside lung volume measurement for estimation of alveolar recruitment. PMID- 22310872 TI - The sensitivity of neutrophil CD64 expression as a biomarker of bacterial infection is low in critically ill patients. AB - PURPOSE: CD64 expression on the surface of neutrophils has recently been proposed as an early marker of bacterial infection. The goal of this study was to determine whether the CD64 index allows differentiation of bacterial sepsis from viral and fungal sepsis and other inflammatory states in a critical-care setting. METHODS: This was an observational prospective study conducted in a medical ICU of a university hospital. All patients admitted between September 2009 and March 2010 with at least two criteria for systemic inflammatory response syndrome (SIRS) were eligible for inclusion. Upon admission, hematological exams were conducted by flow cytometry, allowing quantification of CD64 expression (Leuko64TM kit, Trillium Diagnostics LLC, USA). ROC curve analysis was performed to evaluate the utility of the CD64 index in the diagnosis of bacterial infection. Patients with suspected infection were excluded when infection could not be microbiologically confirmed. RESULTS: Our study included 293 patients with a SAPS II score of 45 (31-59). Bacterial infection was found in 148 patients and SIRS or non-bacterial infection was documented in 145 patients. A CD64 index greater than 2.2 predicted bacterial infection with a sensitivity and specificity of 63% (55-71%) and 89% (83-94%), respectively. The area under the ROC curve was 0.8 (0.75-0.84). Positive and negative likelihood ratios were 5.7 (5.0-6.5) and 0.4 (0.3-0.7), respectively. CONCLUSIONS: The CD64 index is specific for bacterial infection among ICU patients. As a result of its weak sensitivity, the CD64 index may not be practically recommended, but it may be useful in combination with a more sensitive biological marker. PMID- 22310873 TI - Prognostic implications of tissue oxygen saturation in human septic shock. AB - PURPOSE: To analyze the prognostic value of tissue oxygen saturation (StO(2)) in septic shock patients with restored mean arterial pressure (MAP). METHODS: This was a prospective observational study of patients admitted to the ICU in the early phase of septic shock, after restoration of MAP. Demographic data, severity score, hemodynamics, blood lactate, acid-base status, and StO(2) were measured at inclusion followed by a transient vascular occlusion test (VOT) to obtain the StO(2)-deoxygenation (DeOx) and StO(2)-reoxygenation (ReOx) rates. Sequential organ failure assessment (SOFA) score was measured at inclusion and after 24 h. RESULTS: Thirty-three patients were studied. StO(2) was 76 +/- 10%, DeOx -12.2 +/ 4.2%/min, and ReOx 3.02 +/- 1.70%/s. MAP showed a significant correlation with VOT-derived slopes (r = -0.4, p = 0.04 for DeOx; and r = 0.55, p < 0.01 for ReOx). After 24 h, 17 patients (52%) had improved SOFA scores. Patients who did not improve their SOFA showed less negative DeOx values at inclusion. The association between DeOx and SOFA evolution was not affected by MAP. Both DeOx and ReOx impairment correlated with longer ICU stay (r = 0.44, p = 0.05; and r = 0.43, p = 0.05, respectively). CONCLUSIONS: In a population of septic shock patients with restored MAP, impaired DeOx was associated with no improvement in organ failures after 24 h. Decrements in DeOx and ReOx were associated with longer ICU stay. DeOx and ReOx were linked to MAP, and thus, their interpretation needs to be made relative to MAP. PMID- 22310874 TI - Green synthesis of Pt/CeO2/graphene hybrid nanomaterials with remarkably enhanced electrocatalytic properties. AB - We developed a facile strategy for clean synthesis of Pt/CeO(2)/graphene nanomaterials with remarkably enhanced catalytic properties. The graphene oxide (GO) could be used as an oxidant to oxidize Ce(3+) into CeO(2) NPs, and l-lysine was used as a linker to realize the in situ growth of Pt NPs around CeO(2) NPs dispersed on graphene. PMID- 22310875 TI - Surgical intervention for corneal involvement in xeroderma pigmentosa. PMID- 22310876 TI - Choroidal tuberculoma in a patient with ocular Behcet disease. AB - Behcet disease is a chronic relapsing inflammatory disease affecting many different organs. Ocular involvement is quite common in the course of Behcet disease and is frequently manifested by bilateral panuveitis and retinal vasculitis. Medications such as corticosteroids and immunosuppressive agents are used to reduce inflammation in patients with posterior or panuveitis. Chronic immunosuppression is a risk factor for systemic infections. We report a case of choroidal tuberculoma associated with tuberculosis in a patient with ocular Behcet disease. A 25-year-old female with known ocular Behcet disease contracted tuberculosis 3 months earlier. She had been receiving methotrexate and oral steroids. Funduscopy of the left eye revealed a choroidal tuberculoma located superonasally to the optic disc. Fluorescein angiography showed a central area of hypofluorescence surrounded by a hyperfluorescent zone. Since she was already receiving antituberculosis treatment combined with oral steroids, the same treatment was continued. Diagnosis of the other diseases that may cause uveitis in patients with Behcet disease should not be missed. This is especially important since immunosuppressive drugs, that cause an increased incidence of systemic infections, are the common treatment of choice for patients with Behcet disease. PMID- 22310877 TI - Effect of terbutaline on latency period in preterm premature rupture of membranes. AB - AIMS: To assess whether terbutaline is able to prolong the latency period in women with preterm premature rupture of membranes (PPROM) and compare maternal and neonatal morbidity and mortality in the terbutaline and nontocolysis groups. METHODS: This study retrospectively analyzed data from women with singleton pregnancies (gestational ages between 28 and 34 weeks) suffering from PPROM from January 1998 to December 2009. RESULTS: A total of 163 cases of PPROM were analyzed; there were 61 cases (37.4%) in the terbutaline group and 102 cases (62.6%) in the nontocolysis group. The median latency period was comparable in the two groups (78 vs. 75 h, p = 0.44). The percentage of patients who did not deliver within 48 h was significantly higher in the terbutaline group compared with the nontocolysis group (78.7 vs. 62.7%, p = 0.03). There were no differences in maternal morbidity and mortality, and neonatal mortality between the two groups. Interestingly, neonatal infectious morbidity was significantly higher in the terbutaline group when compared with the nontocolysis group. CONCLUSIONS: Terbutaline cannot prolong the latency period in PPROM. There were no differences in maternal morbidity and mortality. However, neonatal infectious morbidity was higher in the terbutaline group. PMID- 22310878 TI - Antifibrotic role of HGF in sarcoidosis. AB - BACKGROUND: Pulmonary sarcoidosis has a variable course ranging from self limiting disease to progressive fibrosis. Activation of fibroblasts, myofibroblast transformation, and matrix production may contribute to pulmonary damage in sarcoidosis. These processes are influenced by pulmonary cytokines which can be measured in bronchoalveolar lavage fluid (BALF). In order to clarify the incompletely understood fibrotic process in sarcoidosis, we classified activity of sarcoidosis according to WASOG criteria, measured TNF-alpha, IL-6, and HGF in BALF, and assessed the effect of HGF and BALF on proliferation and matrix production of human lung fibroblasts. RESULTS: BALF was obtained from 34 consecutive patients with sarcoidosis. BALF of active sarcoidosis contained elevated levels of TNF-alpha, HGF, and IL-6 and stimulated fibroblast proliferation. BALF of inactive sarcoidosis, but not of active sarcoidosis, stimulated the production of matrix proteins. HGF levels in inactive sarcoidosis were below those of control patients. HGF suppressed TGF-beta-induced matrix expression and transformation of fibroblasts into myofibroblasts. CONCLUSION: Prevention of TGF-beta-induced myofibroblast transformation may account for the inhibitory effect of HGF on matrix production. The strong fibrogenic effect of BALF of inactive sarcoidosis corresponds to the worse clinical course of inactive sarcoidosis compared with active disease and may be related to a lack of protective HGF. PMID- 22310879 TI - Chronic sinopulmonary inflammatory diseases in adults with undetectable serum IgE in inner-city Chicago: a preliminary observation. AB - BACKGROUND: The association between undetectable serum total IgE level and chronic upper and lower respiratory tract inflammatory diseases is uncertain. We sought to determine whether chronic sinopulmonary inflammatory diseases are present in adult patients with undetectable serum total IgE who reside in inner city Chicago, IL, USA. METHODS: Medical records of patients aged >=18 years with reported serum total IgE levels <2 and >=2,000 kU/L who were diagnosed with rhinitis, chronic rhinosinusitis, asthma, and COPD at the University of Illinois Medical Center and Jesse Brown VA Medical Center, Chicago, IL, between 2005 and 2009 were reviewed. RESULTS: Seventeen patients with serum total IgE <2 kU/L and 17 patients with serum total IgE >=2,000 kU/L, were identified. Ten of 17 patients (59%) with serum total IgE <2 kU/L were diagnosed with chronic sinopulmonary inflammatory diseases, three with chronic rhinosinusitis, four with asthma, one with asthma/COPD, and two with COPD. Twelve of 17 patients (71%) with serum total IgE >=2,000 kU/L were diagnosed with chronic sinopulmonary inflammatory diseases, three with allergic rhinitis, four with asthma, four with asthma/COPD, and one with COPD. None of the patients reported recurrent sinopulmonary infections. The difference in the number of patients with chronic sinopulmonary inflammatory diseases between both groups was not statistically significant (p = 0.48). CONCLUSIONS: Chronic rhinosinusitis and asthma are present in adult patients with undetectable serum total IgE who reside in inner city Chicago. Whether this represents a biomarker of distinct chronic rhinosinusitis and asthma phenotypes in this population remains to be determined. PMID- 22310880 TI - Red cell distribution width in patients with obstructive sleep apnea syndrome. AB - BACKGROUND: Red cell distribution width (RDW) has been shown to be associated with adverse outcomes in left-sided heart failure, pulmonary hypertension, and in patients in the ICU. However, the role of RDW is unknown in patients with obstructive sleep apnea syndrome (OSAS), especially in OSAS patients with cardiovascular diseases. METHODS: One hundred thirty-seven patients were investigated by polysomnography (PSG) for OSAS. The patients were classified as a control group or as the OSAS group according to the apnea-hypopnea index (AHI). The RDW, hemoglobin level, and mean corpuscular volume (MCV) were determined. C reactive protein (CRP) levels were measured. RESULTS: The RDW values were higher in the OSAS group than in the controls [13.6% (12-23%) vs. 12.9% (11.7-14.5%), p=0.003]. The RDW values were higher in patients with cardiovascular diseases [13.7% (11.7-23.2%) vs. 13.2% (12-16.9%), p=0.001]. RDW >= 13.6% (odds ratio [OR] =1.5 [95% CI = 1.0-2.0], p = 0.014) was found to be associated with increased risk for cardiovascular disease in patients with OSAS on multivariate analysis. It was also shown that there was a significant correlation between the RDW and the AHI (r=0.272), age (r=0.362), mean SaO(2) (r=0.375), systolic pulmonary artery pressure (r=0.435), and CRP level (r=0.275) in study population. CONCLUSIONS: RDW is a newly recognized and widely available diagnostic tool with no additional cost over the routinely performed hemogram. RDW is independently associated with cardiovascular disease in patients with OSAS in our cross sectional study. PMID- 22310881 TI - Pregnancy-related pelvic girdle pain and its relationship with relaxin levels during pregnancy: a systematic review. AB - PURPOSE: The present systematic review assessed the level of evidence for the association between relaxin levels and pregnancy-related pelvic girdle pain (PPGP) during pregnancy. METHODS: PRISMA guidelines were followed to conduct this systematic review. Electronic search was carried out using six different databases. Observational cohorts, cross-sectional or case-control studies focused on the association between relaxin levels and PPGP during pregnancy were included. Studies selection was conducted by two reviewers who screened firstly for titles, then for abstracts and finally for full articles. Risk of bias was assessed using the Newcastle-Ottawa scale and the quality of evidence by the guidelines proposed by the Cochrane back review group. RESULTS: 731 references were identified. Six articles met the inclusion criteria and were considered for this systematic review. The main reason for the studies exclusion was PPGP related to gynaecological reasons. Five studies were case-control and one study was a prospective cohort. Four studies were ranked as high while two were ranked as low quality. Among the high quality studies, three found no association between PPGP and relaxin levels. CONCLUSIONS: Based on these findings, the level of evidence for the association between PPGP and relaxin levels was found to be low. PPGP assessment and controlling for risk factors were found to increase bias leaving uncertainty in interpretation of these findings and a need for further research. PMID- 22310882 TI - Increase in spinal longitudinal length by correction surgery for adolescent idiopathic scoliosis. AB - PURPOSE: One of the downsides of spinal correction surgery for adolescent idiopathic scoliosis (AIS) is the cessation of spinal longitudinal growth within the fused levels in growing children. However, the surgery itself has the potential to increase spinal longitudinal length by correcting the curvature. The purpose of this study was to evaluate the correlation between curve correction and increased spinal longitudinal length by corrective surgery for AIS. METHODS: This study included 208 consecutive patients (14 male, 194 female) with AIS who underwent posterior or anterior correction and fusion surgeries. Mean age at the time of surgery was 15.7 +/- 3.3 years (range 10-20 years). Patients with hyperkyphosis of more than 40 degrees were excluded. All patients had main curves in the thoracic spine (Lenke type 1 or 2). Forty-three patients underwent anterior spinal correction and fusion (ASF) and 164 underwent posterior spinal correction and fusion (PSF). The mean preoperative height was 154.7 +/- 6.9 cm (range 133-173 cm). Pre and postoperative PA standing X-ray films were used to measure the Cobb angle and spinal length between the end vertebrae of the main thoracic curve, and between T1 and L5. The patients were divided into ASF and PSF groups, within which correlations between the Cobb angle correction and spinal length increase were evaluated. RESULTS: In the ASF group, the mean preoperative Cobb angle of the main thoracic curve was 54.9 +/- 8.3 degrees (range 41-83 degrees ) and it was corrected to 19.7 +/- 9.5 degrees (range 0-47 degrees ) with a mean correction of 35.2 +/- 11.1 degrees (range 10-74 degrees ) after surgery. The mean increase in the length of the main thoracic curve was 1.5 +/- 4.6 mm (range -8 to 13 mm), and the mean increase in T1-L5 length was 16.6 +/- 7.7 mm (range -3 to 51 mm). Significant correlation between the correction of the Cobb angle and increase in T1-L5 length was observed, with a correlation coefficient of 0.44. In the PSF group, the mean preoperative Cobb angle of the main thoracic curve was 58.8 +/- 11.6 degrees (range 36-107 degrees ) and it was corrected to 17.1 +/- 7.6 degrees (range 10-49 degrees ), with a mean correction of 41.7 +/- 10.2 degrees (range 21-73 degrees ) after surgery. The mean increase in the length of the main thoracic curve was 14.0 +/- 5.2 mm (range 0-42 mm), and the mean increase in T1-L5 length was 32.4 +/- 10.8 mm (10-61 mm). Correlation between the correction of the Cobb angle and increase in T1-L5 length was high, with a correlation coefficient of 0.64. The increase in T1-L5 length could be calculated by the following formula based on linear regression analysis: increase in T1-L5 length (mm) = correction of the Cobb angle (o) * 0.77. CONCLUSION: Spinal longitudinal length was significantly increased after surgery in both the ASF and PSF groups. Correction of the Cobb angle and increase in T1-L5 length were highly correlated with each other, especially in the PSF group. PMID- 22310883 TI - Age-related changes in osseous anatomy, alignment, and range of motion of the cervical spine. Part I: Radiographic data from over 1,200 asymptomatic subjects. AB - PURPOSE: This study aimed to establish radiographic standard values for cervical spine morphometry, alignment, and range of motion (ROM) in both male and female in each decade of life between the 3rd and 8th and to elucidate these age-related changes. METHODS: A total of 1,230 asymptomatic volunteers underwent anteroposterior (AP), lateral, flexion, and extension radiography of the cervical spine. There were at least 100 men and 100 women in each decade of life between the 3rd and 8th. AP diameter of the spinal canal, vertebral body, and disc were measured at each level from the 2nd to 7th cervical vertebra (C2-C7). C2-C7 sagittal alignment and ROM during flexion and extension were calculated using a computer digitizer. RESULTS: The AP diameter of the spinal canal was 15.8 +/- 1.5 [mean +/- standard deviation (SD)] mm at the mid-C5 level, and 15.5 +/- 2.0 mm at the C5/6 disc level. The disc height was 5.8 +/- 1.3 mm at the C5/6 level, which was the minimum height, and the maximum height was at the C6/7 level. Both the AP diameter of the spinal canal and disc height decreased gradually with increasing age. The C2-C7 sagittal alignment and total ROM were 13.9 +/- 12.3 degrees in lordosis and 55.3 +/- 16.0 degrees , respectively. The C2-C7 lordotic angle was 8.0 +/- 11.8 degrees in the 3rd decade and increased to 19.7 +/- 11.3 in the 8th decade, whereas the C2-C7 ROM was 67.7 +/- 17.0 degrees in the 3rd decade and decreased to 45.0 +/- 12.5 in the 8th decade. The extension ROM decreased more than the flexion ROM, and lordotic alignment progressed with increasing age. There was a significant difference in C2-C7 alignment and ROM between men and women. CONCLUSIONS: The standard values and age-related changes in cervical anatomy, alignment, and ROM for males and females in each decade between the 3rd and 8th were established. Cervical lordosis in the neutral position develops with aging, while extension ROM decreases gradually. These data will be useful as normal values for the sake of comparison in clinical practice. PMID- 22310884 TI - Rhabdomyolysis after heterotopic ossification: an unusual complication in a spinal cord injured patient. AB - PURPOSE: Loss of joint mobility, resulting loss of function peripheral nerve entrapment and pressure sores are the known complications of heterotopic ossification. METHODS: We reported about a 32-year-old male patient, referred to our clinic presenting with incomplete tetraplegia after a motorcycle accident. The patient developed a HO in both hips 19 days after injury. Single-dose radiation therapy with 7 Gy with an electrode voltage of 15 MeV was performed. RESULTS: One month after radiation therapy, the patient developed a fever of 104oF and blood tests showed increased C-reactive protein (CRP), creatinine kinase (CK), serum myoglobin and dark-colored urine due to myoglobinuria. Further diagnostic measures showed only massive recurrent HO. With the suspicion of a possible case of rhabdomyolysis due to the severe muscular distension caused by the recurrent HO, the patient was transferred to our intermediate care unit for further treatment. Forced diureses were applied to reduce the high levels of CK in blood. However, laboratory monitoring showed a further increase in CRP, CK (15,000 U/l) and myoglobin. A repeated radiation therapy was undertaken in a time interval of 14 days. After radiation therapy, a control MRI was performed and no signs of florid HO were visualized, CRP, CK, myoglobin, as well as body temperature and urine colour, had returned to normal and the patient was feeling well. CONCLUSIONS: We report the case of our patient to increase awareness among physicians and training staff working with patients with a spinal cord injury to expedite the diagnosis of rhabdomyolysis in the setting of HO and SCI. PMID- 22310885 TI - The correlation between coronal balance and neuroaxial abnormalities detected on MRI in adolescent idiopathic scoliosis. AB - INTRODUCTION: The indications for magnetic resonance imaging in presumed adolescent idiopathic scoliosis (AIS) have not been established, with some studies suggesting that rates of spinal cord abnormalities are low and question the use of the routine MRI in AIS. OBJECTIVE: Given the restraints on MRI resources the authors performed a retrospective audit to see if the presence of coronal or sagittal misbalance-balance could be used as a surrogate marker for the presence of spinal cord abnormalities in this patient group and hence reduce the need for unnecessary MRI scans. METHODS: We performed a retrospective review of imaging of patients with AIS at our centre over a 2-year-period. All MRI scans were reported by the senior author and the presence of spinal cord abnormalities noted. All plain films were assessed by a senior SpR and ST2 orthopaedic surgeons for Cobb angle, coronal balance, sagittal balance and Lenke classification. RESULTS: A total of 171 patients were identified with AIS. Of these, a total of 15 patients (9%) were found to have neural axis anomalies on MRI including syringomyelia, Chiari malformations and dural ectasia. The average Cobb angle was 44.9 degrees with coronal balance varying from 67.2 mm left to 40.2 mm right. Sagittal balance varied from 125 mm negative to 83 mm positive. No correlation was found between coronal/sagittal misbalance and the presence of neural axis anomalies. CONCLUSIONS: Our audit demonstrates that neither coronal nor sagittal misbalance should be used as an indicator of neural axis abnormalities. PMID- 22310886 TI - Dynamic imine chemistry. AB - Formation of an imine--from an amine and an aldehyde--is a reversible reaction which operates under thermodynamic control such that the formation of kinetically competitive intermediates are, in the fullness of time, replaced by the thermodynamically most stable product(s). For this fundamental reason, the imine bond has emerged as an extraordinarily diverse and useful one in the hands of synthetic chemists. Imine bond formation is one of a handful of reactions which define a discipline known as dynamic covalent chemistry (DCC), which is now employed widely in the construction of exotic molecules and extended structures on account of the inherent 'proof-reading' and 'error-checking' associated with these reversible reactions. While both supramolecular chemistry and DCC operate under the regime of reversibility, DCC has the added advantage of constructing robust molecules on account of the formation of covalent bonds rather than fragile supermolecules resulting from noncovalent bonding interactions. On the other hand, these products tend to require more time to form--sometimes days or even months--but their formation can often be catalysed. In this manner, highly symmetrical molecules and extended structures can be prepared from relatively simple precursors. When DCC is utilised in conjunction with template-directed protocols--which rely on the use of noncovalent bonding interactions between molecular building blocks in order to preorganise them into certain relative geometries as a prelude to the formation of covalent bonds under equilibrium control--an additional level of control of structure and topology arises which offers a disarmingly simple way of constructing mechanically-interlocked molecules, such as rotaxanes, catenanes, Borromean rings, and Solomon knots. This tutorial review focuses on the use of dynamic imine bonds in the construction of compounds and products formed with and without the aid of additional templates. While synthesis under thermodynamic control is giving the field of chemical topology a new lease of life, it is also providing access to an endless array of new materials that are, in many circumstances, simply not accessible using more traditional synthetic methodologies where kinetic control rules the roost. One of the most endearing qualities of chemistry is its ability to reinvent itself in order to create its own object, as Berthelot first pointed out a century and a half ago. PMID- 22310887 TI - Isoform specific regulation of divalent metal (ion) transporter (DMT1) by proteasomal degradation. AB - Divalent metal ion transporter (DMT1) is the major transporter for iron entrance into mammalian cells and iron exit from endosomes during the transferrin cycle. Four major mRNA isoforms correspond to four protein isoforms, differing at 5'/3' and N-/C-termini, respectively. Isoforms are designated 1A versus 1B reflecting where transcription starts or +iron responsive element (+IRE) versus -IRE reflecting the presence/absence of an IRE in the 3' end of the mRNA. These differences imply regulation at transcriptional and posttranscriptional levels. Many proteins are degraded by a ubiquitination-dependent mechanism. Two different ubiquitin ligases (E3s) appear to be involved in DMT1 ubiquitination: Parkin or neuronal precursor cell-expressed developmentally downregulated 4 (Nedd4) family E3s which often utilize Nedd4 family interacting protein-1 and -2 (Ndfip1 and 2) to ubiquitinate their substrate proteins. Prior data suggest that Parkin ubiquitinates 1B DMT1 but not 1A DMT1 while Nedd4/Ndfips ligate ubiquitin to DMT1 in the duodenum where 1A/+IRE DMT1 predominates. Our assay for whether these systems target DMT1 depends on two HEK293 cell lines that express permanently transfected 1A/+IRE DMT1 or 1B/-IRE DMT1 after induction by doxycycline. Transient transfection with a Parkin construct before induction diminishes 1B/ IRE DMT1 detected by immune-blots but not 1A/+IRE DMT1. Mutant Parkin serves as a control that does not affect DMT1 levels. Thus DMT1 regulation in an isoform specific fashion can occur by ubiquitination and the events involved have implications for DMT1 function and disease processes. PMID- 22310892 TI - Sex and the singular DM domain: insights into sexual regulation, evolution and plasticity. AB - Most animals reproduce sexually, but the genetic and molecular mechanisms that determine the eventual sex of each embryo vary remarkably. DM domain genes, which are related to the insect gene doublesex, are integral to sexual development and its evolution in many metazoans. Recent studies of DM domain genes reveal mechanisms by which new sexual dimorphisms have evolved in invertebrates and show that one gene, Dmrt1, was central to multiple evolutionary transitions between sex-determining mechanisms in vertebrates. In addition, Dmrt1 coordinates a surprising array of distinct cell fate decisions in the mammalian gonad and even guards against transdifferentiation of male cells into female cells in the adult testis. PMID- 22310893 TI - Differentiation: Nuclear pores at the core. PMID- 22310895 TI - Disease genetics: Sequencing for diagnosis. PMID- 22310894 TI - Human genetic susceptibility to infectious disease. AB - Recent genome-wide studies have reported novel associations between common polymorphisms and susceptibility to many major infectious diseases in humans. In parallel, an increasing number of rare mutations underlying susceptibility to specific phenotypes of infectious disease have been described. Together, these developments have highlighted a key role for host genetic variation in determining the susceptibility to infectious disease. They have also provided insights into the genetic architecture of infectious disease susceptibility and identified immune molecules and pathways that are directly relevant to the human host defence. PMID- 22310896 TI - Metachronous colorectal cancer in Taiwan: analyzing 20 years of data from Taiwan Cancer Registry. AB - BACKGROUND: The risk of metachronous colorectal cancer in patients with colorectal cancer is higher than the rate of sporadic colorectal cancer in the average population. We conducted a large-scale, population-based study, with many more clinical cases than in previously published studies, to calculate the incidence of metachronous colorectal cancer. METHODS: This is a retrospective study based on data obtained from the Taiwan Cancer Registry from 1988 to 2007. Between 1988 and 2002, we analyzed 70,906 patients who were diagnosed with colon or rectal cancer and traced the occurrence of metachronous lesions with at least 5 years of follow-up. RESULTS: Of these patients, 1,192 (730 males, 462 females; mean age 62.73 +/- 12.92 years) developed metachronous cancers. The 15-year cumulative incidence of metachronous cancer was 1.68%. Within 2 years of the index cancer, 51.69% of the metachronous cancers appeared, and 61.27% of the metachronous cancers appeared within 3 years. CONCLUSIONS: Most metachronous lesions were noted within 3 years of initial diagnosis of the index cancer. Surveillance colonoscopy to ensure the absence of metachronous disease is essential for patients after curative surgery within 1 year, especially for those patients who did not receive complete colonoscopy before their first operation for colorectal cancer. PMID- 22310897 TI - The efficacy of caffeine-potentiated chemotherapy in clear cell sarcoma. PMID- 22310898 TI - Definitive radiation therapy for invasive carcinoma of the vagina: impact of high dose rate intracavitary brachytherapy. AB - BACKGROUND: This study was designed to evaluate the efficacy of definitive radiation therapy (RT) for invasive carcinoma of the vagina. METHODS: Twenty-six patients with invasive carcinoma of the vagina who received RT were studied retrospectively. The median age was 68 years. The pathologic subtype of vaginal carcinoma was squamous cell carcinoma in 24 patients, adenosquamous cell carcinoma in one patient, and adenocarcinoma in one patient. The distribution of clinical stage according to the International Federation of Gynecology and Obstetrics staging system was as follows: stage I, seven patients; stage II, 10 patients, stage III, seven patients; and stage IVA, two patients. Twenty patients received external beam radiation therapy (EBRT) combined with high-dose rate intracavitary brachytherapy (HDR-ICBT), and three received EBRT alone. The remaining three patients with stage I disease were given HDR-ICBT alone. The median dose was 50 Gy for EBRT, and 23 Gy for HDR-ICBT. Systemic chemotherapy was administered concurrently with RT to three patients. RESULTS: The median follow up was 90 months. The initial rate of response to RT was 100%, and complete remission was attained in 21 patients (81%). The 5-year overall survival rate (OS) and the median survival time of the 26 patients were 57% and 97 months, respectively. The 5-year OS for the three patients who received HDR-ICBT alone was 100%. Severe toxicity occurred in three patients-grade 3 rectal hemorrhage in one, grade 3 cystitis in one, and grade 4 cystitis in one. CONCLUSIONS: Our results demonstrated that definitive RT with HDR-ICBT is effective for invasive carcinoma of the vagina, with acceptable toxicity. PMID- 22310899 TI - Facile synthesis of TiO2/graphene composites for selective enrichment of phosphopeptides. AB - TiO(2)/graphene composites were synthesized through a simple one-step hydrothermal reaction and successfully used to selectively capture phosphopeptides from peptide mixtures for matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis. PMID- 22310900 TI - Mutation identification of the DSPP in a Chinese family with DGI-II and an up-to date bioinformatic analysis. AB - In this study, through linkage analysis of a four-generation Chinese family with multiple members afflicted with DGI (type II), we identified a novel missense mutation in DSPP. The mutation was located in exon 2 at the second nucleotide position of the last codon and resulted in a substitution of a proline with a leucine residue (c.50C>T, p.P17L, g.50C>T). To assess the potential effects of this novel mutation, we utilized various bioinformatics analysis programs. The results indicate that the mutation likely affects protein cleavage/trafficking. We also analyzed previously reported mutations of DSPP. In summary, our finding supports that the genomic sequence that corresponds to the P17 residue of DSPP is a mutational hotspot and P17 may be critical for the function of DSPP. PMID- 22310901 TI - The reharvested patellar tendon has the potential for ligamentization when used for anterior cruciate ligament revision surgery. AB - PURPOSE: The aim of the present study was to make an in-depth clinical, radiographical, and histological evaluation of patients who underwent anterior cruciate ligament (ACL) revision surgery with reharvested central third patellar tendon autograft. METHODS: Four patients (two women and two men) underwent ACL revision surgery with reharvested patellar tendon autograft 71 (66-120) months after the primary reconstruction. The patients were followed prospectively and underwent a clinical examination and magnetic resonance imaging (MRI) at two and 10 years. Furthermore, they underwent a second-look arthroscopy involving a biopsy procedure from the reconstructed ACL 3 years after revision surgery. RESULTS: The clinical results were poor both at two and 10 years, but the knees were stable and had a firm endpoint in all four patients in the Lachman test. At the second-look arthroscopy, the graft appeared macroscopically normal in all four patients. Histologically two patients had a normal or close to normal appearance of the reconstructed ACL with no or slight increase in cellularity and vascularity. Two patients had a marked increase in cellularity and vascularity, and the findings revealed that ligamentization was present in all four patients. CONCLUSIONS: The clinical outcome 10 years after ACL revision surgery was poor in these four patients. In contrast, the reharvested patellar tendon appeared close to normal on MRI, and the second-look arthroscopy with the concomitant histological findings revealed that the grafts were viable 3 years after revision. Therefore, the reharvested patellar tendon seems to have the potential for ligamentization when used for ACL revision surgery. LEVEL OF EVIDENCE: Case series, Level IV. PMID- 22310902 TI - CT and enhanced CT in diagnosis of gastrointestinal neuroendocrine carcinomas. AB - OBJECTIVES: To enhance diagnosis of gastrointestinal neuroendocrine carcinomas using CT and contrast-enhanced CT images. METHODS: A total of 44 patients with gastrointestinal neuroendocrine carcinomas, as confirmed by clinical pathology and immunohistochemistry in the Sixth Affiliated People's Hospital of Shanghai Jiao Tong University Shanghai China, were included in the study. CT and enhanced CT scanning were performed, and the resulting images were reviewed and analyzed. RESULTS: Twenty-seven males and 17 females were enrolled. Gastrointestinal involvement included the following: 5 cases located in the middle or inferior segment of the esophagus; 5 in the gastric cardia, 15 in the body of stomach, 6 located in the gastric antrum; 5 located in the Vater papilla of the duodenum; and 8 located in the colon. Among the 44 cases 80%-90% of the lesions had homogeneous density. Totally 81.8% (36/44) cases demonstrated homogeneous enhancement in arterial phases, most of the cases (n = 33) moderately or obviously enhanced. Only 17.2% (8/44) cases appeared as heterogeneous enhancement. And 86.4% cases (n = 38) were further enhanced in the venous phase. The CT images also revealed some of the metastases. Some liver metastasis cases have obvious homogeneous enhancement. CONCLUSIONS: CT and enhanced CT provide useful information regarding gastrointestinal neuroendocrine carcinomas' location, density, enhancement pattern, and some metastasis. These features are helpful to increase the diagnostic accuracy. PMID- 22310903 TI - A graphene-based composite material noncovalently functionalized with a chemiluminescence reagent: synthesis and intrinsic chemiluminescence activity. AB - A bottom-up approach for preparing multifunctional graphene-based materials noncovalently functionalized with CL reagents with aromatic rings such as N (aminobutyl)-N-(ethylisoluminol) (ABEI), luminol and isoluminol is reported. The as-prepared nanocomposites exhibit good CL activity, which may find future applications in analytical, electrochemical and biomedical fields. PMID- 22310904 TI - The degradation mechanism of methyl orange under photo-catalysis of TiO2. AB - The properties of photo-generated reactive species, holes and electrons in bulk TiO(2) (anatase) film and nano-sized TiO(2) were studied and their effects towards decomposing pollutant dye methyl orange (MO) were compared by transient absorption spectroscopies. The recombination of holes and electrons in nano-sized TiO(2) was found to be on the microsecond time scale consistent with previous reports in the literature. However, in bulk TiO(2) film, the holes and electrons were found to be on the order of picoseconds due to ultra fast free electrons. The time-correlated single-photon counting (TCSPC) technique combined with confocal fluorescence microscopy revealed that the fluorescence intensity of MO is at first enhanced noticeably by TiO(2) under UV excitation and soon afterwards weakened dramatically, with the lifetime prolonged. Photo-generated holes in nano sized TiO(2) can directly oxidize MO on the time scale of nanoseconds, while free electrons photo-generated in bulk TiO(2) film can directly inject into MO on the order of picoseconds. Through cyclic voltammetry measurements, it was found that MO can be reduced at -0.28 V and oxidized at 1.4 V (vs. SCE) and this provides thermodynamic evidence for MO to be degraded by electrons and holes in TiO(2). Through comparison of the hole-scavenging effect of MO and water, it was found that in polluted water when MO is above 1.6 * 10(-4) M, the degradation is mainly due to a direct hole oxidation process, while below 1.6 * 10(-4) M, hydroxyl oxidation competes strongly and might exceed the hole oxidation. PMID- 22310905 TI - Prediction of pediatric outcome after prenatal diagnosis and expectant antenatal management of congenital cystic adenomatoid malformation. AB - OBJECTIVE: To determine whether the congenital cystic adenomatoid malformation (CCAM) volume ratio (CVR) is associated with fetal and postnatal outcome after prenatal diagnosis and antenatal expectant management in a provincial tertiary referral center that does not offer fetal surgery. METHODS: Retrospective cohort of 71 consecutive cases of prenatally diagnosed CCAM meeting study criteria (1996 2004). CVR was calculated on the initial ultrasound at the referral center, and associated with hydrops (Fisher's exact test) and a composite adverse postnatal outcome consisting of death, intubation for respiratory distress, extracorporeal membrane oxygenation, non-elective surgery for symptomatology, or respiratory infection requiring hospital admission (Mann-Whitney test). RESULTS: A CVR > 1.6 was significantly associated with hydrops (p = 0.003). In addition, the CVR was significantly associated with the composite adverse postnatal outcome (p = 0.004) at a mean age of follow-up of 41 months (range < 1-117 months). For CVR and postnatal outcome, the area-under-the-curve receiver operating characteristic was 0.81 (95% CI 0.69-0.93, p = 0.006), and choosing a CVR cut-off of < 0.56, the negative predictive value was 100% (95% CI 0.85-1.00). CONCLUSION: In a provincial referral center with antenatal expectant management of CCAM, the CVR was associated with hydrops and postnatal outcome, with a CVR < 0.56 predictive of good prognosis after birth. PMID- 22310906 TI - Developmental profiles of infants and toddlers with autism spectrum disorders identified prospectively in a community-based setting. AB - This prospective, longitudinal, study charted the developmental profiles of young children with Autism Spectrum Disorders (ASD) identified through routine developmental surveillance. 109 children with Autistic Disorder (AD), 'broader' ASD, and developmental and/or language delays (DD/LD) were assessed using the Mullen Scales of Early Learning (MSEL) at 12-months (n = 10 assessments), 18 months (n = 45 assessments), and 24-months (n = 99 assessments). The children with AD performed most poorly, overall, than the ASD and DD/LD groups on the MSEL. Furthermore, the children with AD/ASD displayed an uneven cognitive profile, with poorer performance on verbal (particularly receptive language) relative to nonverbal skills. There was also evidence of developmental slowing in verbal skills from 18- to 24-months for children on the spectrum, especially those with AD. Given that the poor receptive, relative to expressive, language profile emerges very early in life for children with AD/ASD, this cognitive profile may serve as an additional red flag to social attention and communication deficits. Receptive language should therefore be stringently monitored in any developmental surveillance program for autism spectrum disorders in the second year of life. PMID- 22310907 TI - Inclusion and dielectric properties of a vinylidene fluoride oligomer in coordination nanochannels. AB - The dynamics of oligo(vinylidene fluoride) (OVDF) confined in regular nanochannels of a porous coordination polymer (PCP) was studied by means of dielectric spectroscopy. The OVDF chains in the PCP nanopores showed two Arrhenius-type relaxation processes at lower temperatures than the relaxation temperature observed for the neat OVDF, showing the enhanced mobility of the confined OVDF. PMID- 22310908 TI - Impact of measurement error in radon exposure on the estimated excess relative risk of lung cancer death in a simulated study based on the French Uranium Miners' Cohort. AB - Measurement error (ME) can lead to bias in the analysis of epidemiologic studies. Here a simulation study is described that is based on data from the French Uranium Miners' Cohort and that was conducted to assess the effect of ME on the estimated excess relative risk (ERR) of lung cancer death associated with radon exposure. Starting from a scenario without any ME, data were generated containing successively Berkson or classical ME depending on time periods, to reflect changes in the measurement of exposure to radon ((222)Rn) and its decay products over time in this cohort. Results indicate that ME attenuated the level of association with radon exposure, with a negative bias percentage on the order of 60% on the ERR estimate. Sensitivity analyses showed the consequences of specific ME characteristics (type, size, structure, and distribution) on the ERR estimates. In the future, it appears important to correct for ME upon analyzing cohorts such as this one to decrease bias in estimates of the ERR of adverse events associated with exposure to ionizing radiation. PMID- 22310909 TI - Computed tomographies and cancer risk in children: a literature overview of CT practices, risk estimations and an epidemiologic cohort study proposal. AB - Radiation protection is a topic of great public concern and of many scientific investigations, because ionizing radiation is an established risk factor for leukaemia and many solid tumours. Exposure of the public to ionizing radiation includes exposure to background radiation, as well as medical and occupational exposures. A large fraction of the exposure from diagnostic procedures comes from medical imaging. Computed tomography (CT) is the major single contributor of diagnostic radiation exposure. An increase in the use of CTs has been reported over the last decades in many countries. Children have smaller bodies and lower shielding capacities, factors that affect the individual organ doses due to medical imaging. Several risk models have been applied to estimate the cancer burden caused by ionizing radiation from CT. All models predict higher risks for cancer among children exposed to CT as compared to adults. However, the cancer risk associated with CT has not been assessed directly in epidemiological studies. Here, plans are described to conduct an historical cohort study to investigate the cancer incidence in paediatric patients exposed to CT before the age of 15 in Germany. Patients will be recruited from radiology departments of several hospitals. Their individual exposure will be recorded, and time-dependent cumulative organ doses will be calculated. Follow-up for cancer incidence via the German Childhood Cancer Registry will allow computation of standardized incidence ratios using population-based incidence rates for childhood cancer. Dose-response modelling and analyses for subgroups of children based on the indication for and the result of the CT will be performed. PMID- 22310910 TI - Viral infection triggers rapid differentiation of human blood monocytes into dendritic cells. AB - Surprisingly little is known about the interaction of human blood mononuclear cells with viruses. Here, we show that monocytes are the predominant cell type infected when peripheral blood mononuclear cells are exposed to viruses ex vivo. Remarkably, infection with vesicular stomatitis virus, vaccinia virus, and a variety of influenza A viruses (including circulating swine-origin virus) induces monocytes to differentiate within 18 hours into CD16(-)CD83(+) mature dendritic cells with enhanced capacity to activate T cells. Differentiation into dendritic cells does not require cell division and occurs despite the synthesis of viral proteins, which demonstrates that monocytes counteract the capacity of these highly lytic viruses to hijack host cell biosynthetic capacity. Indeed, differentiation requires infectious virus and viral protein synthesis. These findings demonstrate that monocytes are uniquely susceptible to viral infection among blood mononuclear cells, with the likely purpose of generating cells with enhanced capacity to activate innate and acquired antiviral immunity. PMID- 22310911 TI - IL-5 promotes induction of antigen-specific CD4+CD25+ T regulatory cells that suppress autoimmunity. AB - Immune responses to foreign and self-Ags can be controlled by regulatory T cells (Tregs) expressing CD4 and IL-2Ralpha chain (CD25). Defects in Tregs lead to autoimmunity, whereas induction of Ag-specific CD4+CD25+ Tregs restores tolerance. Ag-specific CD4+CD25+ FOXP3+Tregs activated by the T helper type 2 (Th2) cytokine, IL-4, and specific alloantigen promote allograft tolerance. These Tregs expressed the specific IL-5Ralpha and in the presence of IL-5 proliferate to specific but not third-party Ag. These findings suggest that recombinant IL-5 (rIL-5) therapy may promote Ag-specific Tregs to mediate tolerance. This study showed normal CD4+CD25+ Tregs cultured with IL-4 and an autoantigen expressed Il 5ralpha. Treatment of experimental autoimmune neuritis with rIL-5 markedly reduced clinical paralysis, weight loss, demyelination, and infiltration of CD4+ (Th1 and Th17) CD8+ T cells and macrophages in nerves. Clinical improvement was associated with expansion of CD4+CD25+FOXP3+ Tregs that expressed Il-5ralpha and proliferated only to specific autoantigen that was enhanced by rIL-5. Depletion of CD25+ Tregs or blocking of IL-4 abolished the benefits of rIL-5. Thus, rIL-5 promoted Ag-specific Tregs, activated by autoantigen and IL-4, to control autoimmunity. These findings may explain how Th2 responses, especially to parasitic infestation, induce immune tolerance. rIL-5 therapy may be able to induce Ag-specific tolerance in autoimmunity. PMID- 22310912 TI - Down-regulated expression of hsa-miR-181c in Fanconi anemia patients: implications in TNFalpha regulation and proliferation of hematopoietic progenitor cells. AB - Fanconi anemia (FA) is an inherited genetic disorder associated with BM failure and cancer predisposition. In the present study, we sought to elucidate the role of microRNAs (miRNAs) in the hematopoietic defects observed in FA patients. Initial studies showed that 3 miRNAs, hsa-miR-133a, hsa-miR-135b, and hsa-miR 181c, were significantly down-regulated in lymphoblastoid cell lines and fresh peripheral blood cells from FA patients. In vitro studies with cells expressing the luciferase reporter fused to the TNFalpha 3'-untranslated region confirmed in silico predictions suggesting an interaction between hsa-miR-181c and TNFalpha mRNA. These observations were consistent with the down-regulated expression of TNFalpha mediated by hsa-miR-181c in cells from healthy donors and cells from FA patients. Because of the relevance of TNFalpha in the hematopoietic defects of FA patients, in the present study, we transfected BM cells from FA patients with hsa miR-181c to evaluate the impact of this miRNA on their clonogenic potential. hsa miR-181c markedly increased the number and size of the myeloid and erythroid colonies generated by BM cells from FA patients. Our results offer new clues toward understanding the biologic basis of BM failure in FA patients and open new possibilities for the treatment of the hematologic dysfunction in FA patients based on miRNA regulation. PMID- 22310913 TI - Second malignancies after multiple myeloma: from 1960s to 2010s. AB - Based on small numbers, recent reports from 3 randomized trials have consistently demonstrated more hematologic malignancies in patients treated with lenalidomide as maintenance (vs placebo). This fact has prompted concern and highlighted the association between multiple myeloma and second malignancies. Furthermore, an excess of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) after multiple myeloma has been known for over 4 decades. Most prior studies have been restricted because of small numbers of patients, inadequate follow-up, and limitations of ascertainment of second malignancies. Although the underlying biologic mechanisms of AML/MDS after multiple myeloma are unknown, treatment related factors are presumed to be responsible. Recently, an excess risk of AML/MDS was found among 5652 patients with IgG/IgA (but not IgM) monoclonal gammopathy of undetermined significance, supporting a role for disease-related factors. Furthermore, there is evidence to suggest that polymorphisms in germline genes may contribute to a person's susceptibility to subsequent cancers, whereas the potential influence of environmental and behavioral factors remains poorly understood. This review discusses current knowledge regarding second malignancies after multiple myeloma and gives future directions for efforts designed to characterize underlying biologic mechanisms, with the goal to maximize survival and minimize the risk for second malignancies for individual patients. PMID- 22310914 TI - Association between protein signals and type 2 diabetes incidence. AB - Understanding early determinants of type 2 diabetes is essential for refining disease prevention strategies. Proteomic technology may provide a useful approach to identify novel protein patterns potentially related to pathophysiological changes that lead up to diabetes. In this study, we sought to identify protein signals that are associated with diabetes incidence in a middle-aged population. Serum samples from 519 participants in a nested case-control selection (167 cases and 352 age-, sex- and BMI-matched normoglycemic control subjects, median follow up 14.0 years) within the Whitehall-II cohort were analyzed by linear matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Nine protein peaks were found to be associated with incident diabetes. Rate ratios for high peak intensity ranged between 0.4 (95% CI, 0.2-0.8) and 4.0 (95% CI, 1.7-9.2) and were robust to adjustment for main potential confounders, including obesity, lipids and C-reactive protein. The proteins associated with these peaks may reflect diabetes pathogenesis. Our study exemplifies the utility of an approach that combines proteomic and epidemiological data. PMID- 22310915 TI - Liver transplantation: Long-term cognitive function improved in MHE after liver transplantation. PMID- 22310916 TI - The role of pharmacogenetics in nonmalignant gastrointestinal diseases. AB - Genetic variation influences the absorption and efflux of drugs in the intestine, the metabolism of drugs in the liver and the effects of these drugs on their target proteins. Indeed, variations in genes whose products have a role in the pathophysiology of nonmalignant gastrointestinal diseases, such as IBD, have been shown to affect the response of patients to therapy. This Review provides an overview of pharmacogenetics in the management of nonmalignant gastrointestinal diseases on the basis of data from clinical trials. Genetic variants that have the greatest effect on the management of patients with IBD involve the metabolism of thiopurines. Variation in drug metabolism by cytochrome P450 enzymes also requires attention so as to avoid drug interactions in patients receiving tricyclic antidepressants and PPIs. Few genotyping tests are currently used in the clinical management of patients with nonmalignant gastrointestinal diseases, owing to a lack of data from clinical trials showing their effectiveness in predicting nonresponse or adverse outcomes. However, pharmacogenetics could have a beneficial role in enabling pharmacotherapy for nonmalignant gastrointestinal diseases to be targeted to the individual patient. PMID- 22310917 TI - Well-differentiated pancreatic neuroendocrine tumors: from genetics to therapy. AB - Well-differentiated pancreatic neuroendocrine tumors (PanNETs) comprise ~1-3% of pancreatic neoplasms. Although long considered as reasonably benign lesions, PanNETs have considerable malignant potential, with a 5-year survival of ~65% and a 10-year survival of 45% for resected lesions. As PanNETs have a low incidence, they have been understudied, with few advances made until the completion of their exomic sequencing in the past year. In this Review, we summarize some of the latest insights into the genetics of PanNETs, and their probable implications in the context of prognosis and therapy. In particular, we discuss two genes (DAXX and ATRX) that have collectively been identified as mutated in >40% of PanNETs, and the biological and prognostic implications of these novel mutations. The identification of recurrent somatic mutations within the mTOR signaling pathway and the therapeutic implications for personalized therapy in patients with PanNETs are also discussed. Finally, this Review outlines state-of-the-art advances in the biology of PanNETs that are of emerging translational importance. PMID- 22310918 TI - Celiac disease: Pediatric celiac disease--is a diagnostic biopsy necessary? PMID- 22310919 TI - Hepatitis: HCV vaccine is successful in a phase I study in healthy volunteers. PMID- 22310920 TI - Central nervous system: a modified immune surveillance circuit? AB - Immune surveillance in the central nervous system (CNS) was considered impossible because: (i) the brain parenchyma is separated from the blood circulation by the blood-brain barrier (BBB); (ii) the brain lacks lymphatic drainage and (iii) the brain displays low major histocompatibility complex class II (MHCII) expression. In this context, the BBB prevents entry of immune molecules and effector cells to the CNS. The absence of lymphatic vessels avoids CNS antigens from reaching the lymph nodes for lymphocyte presentation and activation. Finally, the low MHCII expression hinders effective antigen presentation and re-activation of T cells for a competent immune response. All these factors limit the effectiveness of the afferent and efferent arms necessary to carry out immune surveillance. Nevertheless, recent evidence supports that CNS is monitored by the immune system through a modified surveillance circuit; this work reviews these findings. PMID- 22310921 TI - Maternal immune activation by LPS selectively alters specific gene expression profiles of interneuron migration and oxidative stress in the fetus without triggering a fetal immune response. AB - Maternal immune activation (MIA) is a risk factor for the development of schizophrenia and autism. Infections during pregnancy activate the mother's immune system and alter the fetal environment, with consequential effects on CNS function and behavior in the offspring, but the cellular and molecular links between infection-induced altered fetal development and risk for neuropsychiatric disorders are unknown. We investigated the immunological, molecular, and behavioral effects of MIA in the offspring of pregnant Sprague-Dawley rats given an intraperitoneal (0.25 mg/kg) injection of lipopolysaccharide (LPS) on gestational day 15. LPS significantly elevated pro-inflammatory cytokine levels in maternal serum, amniotic fluid, and fetal brain at 4 h, and levels decreased but remained elevated at 24 h. Offspring born to LPS-treated dams exhibited reduced social preference and exploration behaviors as juveniles and young adults. Whole genome microarray analysis of the fetal brain at 4 h post maternal LPS was performed to elucidate the possible molecular mechanisms by which MIA affects the fetal brain. We observed dysregulation of 3285 genes in restricted functional categories, with increased mRNA expression of cellular stress and cell death genes and reduced expression of developmentally-regulated and brain specific genes, specifically those that regulate neuronal migration of GABAergic interneurons, including the Distal-less (Dlx) family of transcription factors required for tangential migration from progenitor pools within the ganglionic eminences into the cerebral cortex. Our results provide a novel mechanism by which MIA induces the widespread down-regulation of critical neurodevelopmental genes, including those previously associated with autism. PMID- 22310922 TI - Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism. AB - The core symptoms of autism are deficits in social interaction and language, and the presence of repetitive/stereotyped behaviors. We demonstrate that behaviors related to these symptoms are present in a mouse model of an environmental risk factor for autism, maternal infection. We stimulate the maternal immune system by injecting the viral mimic poly(I:C) during pregnancy, and analyze the social and communicative behaviors of the offspring. In one test, young pups respond to a brief separation from the mother with ultrasonic vocalizations (USVs). We find that, compared to pups born to saline-injected mothers, pups born to maternal immune activation (MIA) mothers produce a lower rate of USVs in the isolation test starting at day 8. The quality of the vocalizations is also different; analysis of sound spectrograms of 10 day-old pups shows that male pups from MIA mothers emit significantly fewer harmonic and more complex and short syllables. These communication differences are also apparent in adult offspring. Compared to controls, adult MIA males emit significantly fewer USVs in response to social encounters with females or males, and display reduced scent marking in response to female urine. Regarding a second autism symptom, MIA males display decreased sociability. In a third test of characteristic autism behaviors, MIA offspring exhibit increased repetitive/stereotyped behavior in both marble burying and self grooming tests. In sum, these results indicate that MIA yields male offspring with deficient social and communicative behavior, as well as high levels of repetitive behaviors, all of which are hallmarks of autism. PMID- 22310923 TI - Hysteropexy compared to hysterectomy for uterine prolapse surgery: does durability differ? AB - INTRODUCTION AND HYPOTHESIS: The aim of this study is to assess the impact of hysterectomy on durability of uterine prolapse repair by comparing hysterectomy/uterosacral cuff suspension (VH) to a new vaginal uterosacral hysteropexy (USH). METHODS: A retrospective chart review of uterine prolapse patients after USH or VH with concomitant procedures as indicated was conducted, analyzing Baden-Walker grading of apex, anterior, and posterior compartments (Kaplan-Meier analysis) Baden et al. (Tex Med 64(5):56-58, 1968). RESULTS: A total of 200 charts met criteria. USH women weighed less, were younger, and more constipated with larger rectoceles. Levator parameters did not differ Romanzi et al. (Neurourol Urodyn 18(6):603-612, 1999). Baden-Walker data were entered at recurrence or minimum of 6 months (2.4 months-10 years; median, 1.5 years). All apex durability was 96.4%, with no difference between hysteropexy and cuff suspension (96.0% vs. 96.8%, p = 0.90), cystocele (86.8% vs. 93.8%, p = 0.31), or rectocele (97.8% vs. 100%, p = 0.16) at 2 years. CONCLUSION: In uterine prolapse patients, technically similar uterosacral hysteropexy durability did not differ from hysterectomy-based cuff suspension nor between cohorts for cystocele or rectocele. PMID- 22310924 TI - Solifenacin for overactive bladder: a systematic review and meta-analysis. AB - This study aims to evaluate the efficacy and safety of solifenacin for treating overactive bladder. Randomized controlled trials (RCTs) were identified and extracted from MEDLINE, Embase, and CENTRAL. The quality of the included RCTs was assessed using the Jadad score, and heterogeneity was analyzed using the chi squared test. The data of the included RCTs were collected, extracted, and assessed by our protocol. A total of nine RCTs were identified from the search strategy. Compared with the placebo and tolterodine treatments, both short-term (mostly 12-week) trials indicated that solifenacin significantly reduced urgency episodes, micturitions, and incontinence episodes per 24 h. Compared with the solifenacin (5 mg) group, the solifenacin (10 mg) group was significantly better in terms of the number of micturitions per 24 h. With regard to adverse effects, the patients treated with solifenacin had significantly higher rates of constipation and blurred vision than patients treated with tolterodine. The solifenacin therapy was not inferior to tolterodine in terms of efficacy profiles and had a similar incidence of overall adverse events compared with tolterodine treatment. Solifenacin (5 mg) is thus a recommended dose because of its reported balance between efficacy and acceptable tolerability. PMID- 22310925 TI - Pathophysiology of overactive bladder. AB - Overactive bladder (OAB) is a common disorder that negatively affects the quality of life of our patients and carries a large socioeconomic burden. According to the International Continence Society, it is characterized as urinary urgency, with or without urge incontinence, usually, with frequency and nocturia in the absence of causative infection. The pathophysiology of this disease entity varies between neurogenic, myogenic, or idiopathic factors. This paper provides a review of the contemporary theories behind the pathophysiology of OAB. PMID- 22310926 TI - Combination small molecule PPT1 mimetic and CNS-directed gene therapy as a treatment for infantile neuronal ceroid lipofuscinosis. AB - Infantile neuronal ceroid lipofuscinosis (INCL) is a profoundly neurodegenerative disease of children caused by a deficiency in the lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1). There is currently no effective therapy for this invariably fatal disease. To date, preclinical experiments using single treatments have resulted in incremental clinical improvements. Therefore, we determined the efficacy of CNS-directed AAV2/5-mediated gene therapy alone and in combination with the systemic delivery of the lysosomotropic PPT1 mimetic phosphocysteamine. Since CNS-directed gene therapy provides relatively high levels of PPT1 activity to specific regions of the brain, we hypothesized that phosphocysteamine would complement that activity in regions expressing subtherapeutic levels of the enzyme. Results indicate that CNS-directed gene therapy alone provided the greatest improvements in biochemical and histological measures as well as motor function and life span. Phosphocysteamine alone resulted in only minor improvements in motor function and no increase in lifespan. Interestingly, phosphocysteamine did not increase the biochemical and histological response when combined with AAV2/5-mediated gene therapy, but it did result in an additional improvement in motor function. These data suggest that a CNS-directed gene therapy approach provides significant clinical benefit, and the addition of the small molecule PPT1 mimetic can further increase that response. PMID- 22310927 TI - In search of proof-of-concept: gene therapy for glycogen storage disease type Ia. AB - The emergence of life threatening long-term complications in glycogen storage disease type Ia (GSD-Ia) has emphasized the need for new therapies, such as gene therapy, which could achieve biochemical correction of glucose-6-phosphatase deficiency and reverse clinical involvement. We have developed gene therapy with a novel adeno-associated virus (AAV) vector that: 1) prevented mortality and corrected glycogen storage in the liver, 2) corrected hypoglycemia during fasting, and 3) achieved efficacy with a low number of vector particles in G6Pase deficient mice and dogs. However, the gradual loss of transgene expression from episomal AAV vector genomes eventually necessitated the administration of a different pseudotype of the AAV vector to sustain dogs with GSD-Ia. Further preclinical development of AAV vector-mediated gene therapy is therefore warranted in GSD-Ia. PMID- 22310928 TI - Genetic variation in IL28B is associated with the development of hepatitis B related hepatocellular carcinoma. AB - To evaluate the role of host IL28B (interleukin 28B; interferon lambda 3) single nucleotide polymorphisms (SNPs) in predicting hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) susceptibility, three SNPs in the IL28B gene (rs12979860C/T, rs8099917G/T and rs12980275G/A) were examined in 330 subjects (including 154 HBV-related HCC patients, 86 non-HCC patients with chronic hepatitis B (CHB), 43 HBV self-limited infections and 47 healthy controls). Notably, the frequency of CC homozygosity was 91.5% in healthy controls and 72.9% in CHB, the difference being statistically significant (chi(2) = 6.40, P = 0.01). The statistically difference was seen between healthy controls (91.5%) and HCC (74.7%) (chi(2) = 6.05, P = 0.01). However, this significant finding was not seen between HBV self-limited and healthy controls. Carriers of the minor T allele in rs12979860 had a higher risk of HCC compared with non-carriers (chi(2) = 4.44, P = 0.04). Haplotype analyses revealed significant association between haplotype C T-A and healthy controls, but not with the HCC group (96.6 vs. 82.0%, chi(2) = 6.08, P = 0.01). Analyses of genotype combination and gene-gene interaction showed that there was a positive interaction between rs12979860 and rs12980275, with an OR rate of 11.79 (likelihood test, P = 0.04). Our results suggest that the IL28B rs12979860 C/T polymorphism might affect susceptibility to the chronic HBV infection and progression of HCC. Of note, the T allele and non-CC genotypes have strong predictive effect of increasing susceptibility of chronic HBV infection and HCC. PMID- 22310929 TI - Differential effects of low-dose decitabine on immune effector and suppressor responses in melanoma-bearing mice. AB - BACKGROUND: Low doses of the demethylating agent decitabine have been shown to enhance the sensitivity of tumors to immune effector cells and molecules through upregulation of tumor antigen presentation and apoptotic pathways. Effects on host immune effector and suppressor responses have not been well characterized. METHODS: Mice bearing B16 melanoma were treated with low-dose decitabine, cytokine, interleukin-2 (IL-2), toll-like receptor 9 agonist ODN1826, and/or a viral vectored vaccine targeting the melanoma antigen Trp2. Lymphoid and myeloid effector and suppressor cells were examined both systemically and intratumorally with functional, flow cytometric, and polymerase chain reaction-based assays. RESULTS: Enhancement of tumor growth delay was observed when decitabine was applied sequentially but not concurrently with IL-2. In contrast, complete responses and prolonged survival were observed when decitabine was applied with ODN1826 as therapy and with ODN1826 as a Trp2 vaccine adjuvant. Decitabine decreased natural killer and antigen-specific cellular immune responses when administered concurrently with IL-2 and with ODN1826; the Th1-associated transcription factor Tbet also decreased. T regulatory cells were not affected. When applied concurrently with ODN1826, decitabine increased macrophage cytotoxicity, M1 polarization, and dendritic cell activation. Myeloid-derived suppressor cells were reduced. CONCLUSION: Low-dose decitabine promotes both anti and pro-tumor host immune responses to immunotherapeutics in melanoma-bearing mice. Macrophage effector and dendritic cell activation increase, and myeloid suppressor cells decrease. Lymphoid effector responses, however, can be inhibited. PMID- 22310930 TI - Eleventh international conference on progress in vaccination against cancer (PIVAC-11), 10-13 October 2011, Copenhagen, Denmark. PMID- 22310931 TI - Expression of IL-15 in NK cells results in rapid enrichment and selective cytotoxicity of gene-modified effectors that carry a tumor-specific antigen receptor. AB - Natural killer (NK) cells hold promise for adoptive cancer immunotherapy but are dependent on cytokines such as interleukin (IL)-2 for growth and cytotoxicity. Here, we investigated the consequences of ectopic expression of IL-15 in human NK cells. IL-2 and IL-15 belong to the common gamma chain family of cytokines and have overlapping activities. Transduction of clinically applicable NK-92 cells with lentiviral vectors encoding human IL-15 resulted in predominantly intracellular expression of the cytokine, and STAT5 activation, proliferation and cytotoxicity of the producer cells in the absence of IL-2. Growth of non transduced bystander cells was not supported, allowing rapid enrichment of gene modified cells solely by IL-2 withdrawal. This was also the case upon transduction of NK-92 and NKL cells with a bicistronic lentiviral vector encoding IL-15 and a chimeric antigen receptor (CAR) targeting the pancarcinoma antigen EpCAM. Effector cells co-expressing CAR and IL-15 continued to proliferate in the absence of exogenous cytokines and displayed high and selective cell-killing activity against EpCAM-expressing breast carcinoma cells that were resistant to the natural cytotoxicity of unmodified NK cells. This strategy facilitates rapid isolation and continuous expansion of retargeted NK cells and may extend their potential clinical utility. PMID- 22310932 TI - Binary ionic porphyrin nanosheets: electronic and light-harvesting properties regulated by crystal structure. AB - Crystalline solids self-assembled from anionic and cationic porphyrins provide a new class of multifunctional optoelectronic micro- and nanomaterials. A 1 : 1 combination of zinc(II) tetra(4-sulfonatophenyl)porphyrin (ZnTPPS) and tin(IV) tetra(N-methyl-4-pyridiniumyl)porphyrin (SnTNMePyP) gives porphyrin nanosheets with high aspect ratios and varying thickness. The room temperature preparation of the nanosheets has provided the first X-ray crystal structure of a cooperative binary ionic (CBI) solid. The unit cell contains one and one-half molecules of aquo-ZnTPPS(4-) (an electron donor) and three half molecules of dihydroxy SnTNMePyP(4+) (an electron acceptor). Charge balance in the solid is reached without any non-porphyrinic ions, as previously determined for other CBI nanomaterials by non-crystallographic means. The crystal structure reveals a complicated molecular arrangement with slipped pi-pi stacking only occurring in isolated dimers of one of the symmetrically unique zinc porphyrins. Consistent with the crystal structure, UV-visible J-aggregate bands indicative of exciton delocalization and extended pi-pi stacking are not observed. XRD measurements show that the structure of the Zn/Sn nanosheets is distinct from that of Zn/Sn four-leaf clover-like CBI solids reported previously. In contrast with the Zn/Sn clovers that do exhibit J-aggregate bands and are photoconductive, the nanosheets are not photoconductive. Even so, the nanosheets act as light-harvesting structures in an artificial photosynthesis system capable of reducing water to hydrogen but not as efficiently as the Zn/Sn clovers. PMID- 22310933 TI - Memory T cells in the chronic inflammatory microenvironment of nasal polyposis are hyporesponsive to signaling through the T cell receptor. AB - A majority of T cells from chronic inflammatory tissues derived from patients with nasal polyposis were found to express an effector memory phenotype. We report here that these memory T cells failed to activate NF-kappaB in response to TCR stimulation but responded normally when the proximal TCR signaling molecules were bypassed with PMA and ionomycin. The dysfunction of these cells was associated with a decrease in the phosphorylation of several TCR proximal signaling molecules including ZAP70, Lck and SLP-76. In addition to the disruption in the TCR signaling pathway, the nasal polyp-associated T cells were shown to have a defect in their ability to translocate LAMP-1 to the cell surface. The results presented here establish that the phenotype and anergy of the T cells in the nasal polyp are similar to those which is seen in memory T cells derived from human tumors and other sites of chronic inflammation. PMID- 22310934 TI - Hippocampal drebrin loss in mild cognitive impairment. AB - Alterations in the relative abundance of synaptic proteins may contribute to hippocampal synaptic dysfunction in Alzheimer's disease (AD). The extent to which perturbations in synaptic protein expression occur during the earliest stages of cognitive decline remains unclear. We examined protein levels of presynaptic synaptophysin (SYP) and synaptotagmin (SYT), and postsynaptic drebrin (DRB), a marker for dendritic spine plasticity, in the hippocampus of people with an antemortem clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI) or mild/moderate AD. Although normalized SYP and SYT levels were preserved, DRB was reduced by approximately 40% in the hippocampus of MCI and AD compared to NCI subjects. This differential alteration of synaptic markers in MCI suggests a selective impairment in hippocampal postsynaptic dendritic plasticity in prodromal AD that likely heralds the onset of memory impairment in symptomatic disease. PMID- 22310935 TI - Pregnancy outcomes in oocyte donation recipients: vaginal gel versus intramuscular injection progesterone replacement. AB - PURPOSE: Compare outcomes with vaginal gel versus intramuscular progesterone replacement in donor oocyte recipients. METHODS: A single-center retrospective analysis (January 2004-December 2006) evaluated pregnancy outcomes (serum human chorionic gonadotropin, implantation, clinical pregnancy, delivery, total pregnancy loss rates) for 225 recipients of embryos from donor (aged <32 years) oocytes. Vaginal progesterone gel (Crinone(r) 8%; 90 mg twice daily; n = 105) or intramuscular progesterone (50 mg once daily; n = 120) was started the afternoon of oocyte retrieval and continued until a negative pregnancy test or 10 weeks' gestation. RESULTS: There were no statistically significant differences between groups for the five pregnancy outcomes; numerical results favored vaginal progesterone in all cases. Confidence intervals showed vaginal gel was within, or <1% from, a noninferiority limit of 10% versus intramuscular progesterone for four of five pregnancy outcomes. CONCLUSIONS: Pregnancy outcomes were comparable for progesterone replacement with vaginal gel and intramuscular progesterone in an oocyte donation program. PMID- 22310936 TI - Construction of adjacent spiro-quaternary and tertiary stereocenters through phosphine-catalyzed asymmetric [3+2] annulation of allenoates with alkylidene azlactones. AB - A novel axially chiral spiro-phosphine-catalyzed highly regio-, diastereo- and enantioselective [3+2] cycloaddition of alkylidene azlactones with various allenic esters has been developed, affording the corresponding functionalized spirocyclic products in moderate to excellent yields under mild conditions. These spirocyclic products as masked amino acids can be easily transformed into aspartic amino acid analogues. PMID- 22310937 TI - Median sternotomy for double lung transplantation with cardiopulmonary bypass in seven consecutive patients. AB - We describe our technique of using median sternotomy to perform double lung transplantations with cardiopulmonary bypass. By sparing the respiratory muscles, median sternotomy is probably less invasive and preserves lung function. Furthermore, it causes less long-term discomfort than intercostal thoracotomy. Although exposure of the pleural space is less optimal, abundant pleural adhesions can be dissected, particularly in the left posterior pleural cavity, using pericardial traction stitches, exposing the retrocardiac pleura with minimal manipulation of the heart. PMID- 22310938 TI - Minimally invasive video-assisted versus conventional open thyroidectomy: a systematic review of available data. AB - PURPOSE: Minimally invasive video-assisted thyroidectomy (MIVAT) is now emerging as a novel and less invasive procedure for thyroid diseases. This study conducted a systematic review of the available data to evaluate the safety and efficacy of this new technique over conventional procedure. METHODS: A systematic literature search was performed on Medline, Embase, and The Cochrane Library. Randomized controlled trials comparing the MIVAT with open thyroidectomy were selected and meta-analyzed. RESULTS: Nine RCTs involving 730 patients were included and all were restricted to patients with a thyroid nodule no larger than 4 cm and surgery did not involve lymph node dissection. Both procedures were of similar efficacy in nodule resection. Open surgery had a 1.6 times higher rate of postoperative complications than the novel technique, with no significant difference (P = 0.08), especially in transient recurrent nerve palsy (OR = 0.93, P = 0.87). Although longer operative time was required for MIVAT (MD = 15.0 min, P < 0.00001), patients experienced less postoperative pain, especially in the early postoperative period (MD = -11.52, P = 0.0003). There was also a shorter incision length (MD = -2.36 cm, P < 0.00001), better cosmetic results and greater patient satisfaction in the novel technique group (WD = 2.59; P < 0.00001). CONCLUSIONS: MIVAT is a feasible, practical, and safe alternative with better cosmetic benefits, and it can be performed with an ease of manipulation that is similar to that of conventional neck surgery. PMID- 22310939 TI - Phthalocyanine with a giant dielectric constant. AB - Compound 1 has been prepared by the reaction of 4-nitrophthalonitrile and trans-2 methoxy-4-(2-nitrovinil)phenol by the common method of nucleophilic substitution of an activated nitro group in an aromatic ring. The metallophthalocyanines 2, 3 were prepared by the reaction of a dinitrile derivative with Co(OAc)(2) or Zn(OAc)(2) in DMSO. The lutetium bis-(phthalocyaninato) complex 4 was obtained by treating the dinitrile derivative with lutetium acetate and DBU in 1-hexanol. The new compounds were characterized by elemental analyses, FT-IR, (1)H-NMR, MALDI TOF MS and UV/Vis spectral data. The spectroscopic data of the new compounds were in accordance with the structures. The temperature and frequency dependence of dielectric and conduction properties of the spin coated film of compounds (2-4) have been studied by fabricating metal-Pc-metal structures. The results show that compound 2 has giant dielectric constant. At a low range of frequency and room temperature, epsilon' is found to be equal to 2.33 * 10(6), 1.53 * 10(4) and 1.03 * 10(4) for 2, 3 and 4, respectively. The giant dielectric behavior of 2 is mainly attributed to Maxwell-Wagner polarization. The obtained results also indicated that the frequency dependence of the dielectric permittivity, epsilon'(omega), exhibits non-Debye type relaxation for all temperatures investigated. The ac conductivity results gave a temperature dependent frequency exponent s. The results were compared with the prediction of the Quantum Mechanical Tunneling and Correlated Barrier Hopping models. PMID- 22310940 TI - Link between non-motor symptoms and cognitive dysfunctions in de novo, drug-naive PD patients. AB - Little is known about the relationship between cognitive dysfunctions and the non motor complex in subjects with newly diagnosed untreated Parkinson's disease (PD). The aim of this study was to explore the association between non-motor symptoms (NMS) and cognitive dysfunctions in an incident cohort of de novo, drug naive, PD patients. Sixty-six non-demented, early, untreated PD patients completed a semi-structured interview on NMS and a battery of neuropsychological tests that assess verbal memory, visuospatial abilities, and attention/executive functions. Scores were age- and education-corrected. Patients who failed at least two tests for each cognitive domain were diagnosed as having mild cognitive impairment (MCI). All but three (95.4%) PD patients complained of at least one NMS. A total of 37.8% was diagnosed with MCI. There was a relationship between sleep-NMS and cognitive dysfunctions. Specifically, both REM behavioral sleep disorders (RBD) and insomnia were associated with lower scores on several cognitive tests. Moreover, RBD was closely related to MCI. NMS and MCI are very common even in the early phase of PD, before patients are treated. Given the correlation between sleep disturbances and cognitive impairment, it is possible that sleep symptoms in PD patients might be considered as an early marker of dementia. PMID- 22310941 TI - Analysis of myelinated fibers in human skin biopsies of patients with neuropathies. AB - Given the availability of effective but costly treatment for acquired demyelinating neuropathies, biomarkers for these disorders are urgently needed. Here we aimed to quantify morphological abnormalities of myelinated fibers in skin biopsies from the proximal leg of patients with neuropathies to determine a potential diagnostic role of this method. We used double immunofluorescence to detect myelinated and unmyelinated fibers in thigh skin from 81 patients with polyneuropathy, 19 patients with small fiber neuropathy, and 25 controls. Dermal myelinated fibers were reduced 6.8-fold in patients with polyneuropathy (p < 0.0001). The number of dermal nerve bundles with myelinated fibers was reduced 2.7-fold (p = 0.0025). In small fiber neuropathy, myelinated fibers in dermal nerve bundles were only reduced in the length-dependent type, indicating that this subgroup may represent an early stage of generalized polyneuropathy. Elongated nodes of Ranvier were detectable in demyelinating neuropathies only. Our data suggest that changes in the number and morphology of myelinated fibers in the proximal leg can confirm the diagnosis of neuropathy, and may help to distinguish between demyelinating and axonal neuropathy, and to differentiate pure small fiber neuropathy from early polyneuropathy. PMID- 22310942 TI - Interstitial cystitis: diagnosis and management. AB - Interstitial cystitis/painful bladder syndrome is a chronic condition that causes debilitating bladder pain which can be associated with urgency, frequency and nocturia. Its cause is not clear and it is still a disease diagnosed by exclusion. Oral or intravesical therapies are the main stay of treatment whilst surgical procedures are reserved for refractory cases. This condition usually warrants a multidisciplinary approach for optimum outcome. This article gives an overview of the changes in definition, aetiopathogenesis and available treatments. PMID- 22310943 TI - The impact of plasma fibrinogen levels on patients with vulvar cancer. AB - OBJECTIVE: To investigate the association between plasma fibrinogen levels and clinico-pathological parameters of patients with vulvar cancer and to determine their value as prognostic parameters. STUDY DESIGN: In this retrospective study, we evaluated pretreatment plasma fibrinogen levels in 120 patients with invasive squamous cell vulvar cancer and correlated them with clinico-pathological parameters and patients' survival. RESULTS: Pretreatment plasma fibrinogen levels were directly associated with tumor stage (pT1a vs. pT1b vs. pT2 vs. pT3-4, p=0.001), lymph node involvement (pN0 vs. pN1, p=0.04), and histological grade (G1 vs. G2 vs. G3, p=0.03), but not with patients' age (<= 70 years vs. >70 years, p=0.6). In a multivariate survival analysis, tumor stage (p=0.006/p=0.02) and lymph node involvement (p<0.001/p<0.001), but neither histological grade (p=0.2/p=0.9) nor plasma fibrinogen levels (p=0.6/p=0.6) were associated with disease-free and overall survival, respectively. In a multivariate analysis, patient's age (<= 70 years vs. >70 years) was associated with overall survival (p=0.03) but not with disease-free survival (p=0.1). CONCLUSION: Pretreatment plasma fibrinogen levels were directly associated with tumor stage, lymph node involvement and histological grade. Although we could demonstrate a prognostic value of pretreatment plasma fibrinogen levels on survival, we were unable to establish fibrinogen as an independent prognostic parameter in patients with vulvar cancer. PMID- 22310944 TI - Three-year follow-up results of polypectomy with endometrial ablation in the management of endometrial polyps associated with tamoxifen in Chinese women. AB - OBJECTIVE: The aim of this study was to investigate the role of hysteroscopic polypectomy with endometrial ablation in the management of tamoxifen-associated endometrial polyps in postmenopausal women with a more than 3-year follow-up period. STUDY DESIGN: The medical records of 76 postmenopausal patients on tamoxifen who were performed hysteroscopic polypectomy with endometrial ablation were evaluated more than 3 years after the procedure with recurrence of polyps, recurrent abnormal uterine bleeding and surgical re-intervention. RESULTS: Average follow-up period was 74.91 +/- 20.84 months. No patient underwent hysterectomy, 7 of 76 patients had a surgical re-intervention representing a total of 90.8% avoidance of additional surgery during the follow-up period, and 4 patients had a recurrent endometrial polyp representing the recurrence rate was 5.3%. 3 of 41 patients with postmenopausal bleeding had a recurrent abnormal uterine bleeding representing symptomatic relief rate is 92.7%. The treatment failed in 7 patients who requested surgical re-intervention: 4 patients requested a repeat polypectomy and ablation, 1 patient requested a repeat ablation and 2 patients requested a repeat hysteroscopy with uterine adhesion. No malignant endometrial pathological result was found. CONCLUSIONS: For postmenopausal patients suffering from endometrial polyps associated with tamoxifen, hysteroscopic polypectomy with endometrial ablation continues to be proven as a safe and effective minimally invasive treatment method. The high rate of surgical re-intervention avoidance, great symptomatic relief and low recurrence rate are very encouraging for this technology. PMID- 22310945 TI - A case control study of gene environmental interaction in fetal growth restriction with special reference to organochlorine pesticides. AB - OBJECTIVES: Organochlorine pesticides (OCPs) and oxidative stress are reported to be associated with adverse reproductive outcomes. Glutathione S-transferase (GST) is a polymorphic supergene family involved in the detoxification of numerous toxins including OCPs. OCPs are endocrine disrupter and prenatal exposure to them may be associated with fetal growth restriction (FGR). The objectives of the present study were (i) to determine the frequencies of polymorphic alleles of GSTM1 and GSTT1 genes in women with idiopathic FGR, (ii) to analyze the maternal and cord blood levels of the OCPs, and (iii) to identify the gene environment interaction that increases the risk of FGR. STUDY DESIGN: Maternal and cord blood samples of 50 FGR cases (birth weight <10 percentile for gestational age as per Lubchenco's growth chart) and equal number of normal pregnancies who were occupationally non exposed to OCPs and excluding all the known high risk factors such as anemia, hypertension, antiphospholipid antibody syndrome, medical disease, dietary habit, living style, parity, and BMI. The collected samples at the time of delivery/after delivery were analyzed for OCPs levels by gas chromatography and polymorphic analysis for GSTM1/GSTT1 gene using multiplex PCR. RESULTS: Significantly higher levels of alpha,beta,gamma-HCH and p,p'-DDT were found in maternal blood and significantly higher levels of beta and gamma-HCH and p,p'-DDT were found in cord blood of FGR cases as compared to controls. The genotypic distribution of GSTM1/GSTT1 was almost similar in both the groups, but the frequency of GSTM1-/GSTT1- (null) genotype was significantly higher in FGR cases as compared to controls (p<0.05, OR=6.42). When interaction between GSTM1/GSTT1 genes polymorphism-OCPs levels and birth weight (gene-environment interaction) was ascertained, a significant association was seen between beta-HCH and GSTM1- genotype with reduction in birth weight of 213g. CONCLUSION: Higher levels of OCPs in pregnant women may be considered as an important aetiological factor in 'idiopathic' FGR. GST polymorphism can influence the relationship between prenatal exposure to pesticides and FGR. The present study provides evidence that polymorphism in xenobiotic metabolising genes may modify the effect of environmental health hazards and increase the risk of FGR. PMID- 22310947 TI - Methods for the diagnosis of rupture of the fetal membranes in equivocal cases. PMID- 22310949 TI - Diabetes: glycemic control and outcomes in people with diabetes and CKD. PMID- 22310950 TI - Glomerular disease: perspectives on maintenance therapy in lupus nephritis. PMID- 22310948 TI - Nutrition in patients on peritoneal dialysis. AB - Protein-energy wasting (PEW) is prevalent among patients on dialysis and has emerged as an important risk factor for morbidity and mortality in these patients. Numerous factors, including inflammation, inadequate dialysis, insufficient nutrient intake, loss of protein during dialysis, chronic acidosis, hypercatabolic illness and comorbid conditions, are involved in the development of PEW. The causes and clinical features of PEW in patients on peritoneal dialysis and hemodialysis are comparable; assessment of the factors that lead to PEW in patients receiving peritoneal dialysis is important to ensure that PEW is managed correctly in these patients. For the past 20 years, much progress has been made in the prevention and treatment of PEW. However, the results of most nutritional intervention studies are inconclusive. In addition, the multifactorial and complicated pathogenesis of PEW makes it difficult to assess and treat. This Review summarizes the nutritional issues regarding the causes, assessment and treatment of PEW, with a focus on patients receiving peritoneal dialysis. In addition, an in-depth overview of the results of nutritional intervention studies is provided. PMID- 22310951 TI - Acute kidney injury: findings thwart 'double-hit' hypothesis. PMID- 22310952 TI - Restoring the renal microvasculature to treat chronic kidney disease. AB - Chronic kidney disease is characterized by progressive loss of the renal microvasculature, which leads to local areas of hypoxia and induction of profibrotic responses, scarring and deterioration of renal function. Revascularization alone might be sufficient to restore kidney function and regenerate the structure of the diseased kidney. For revascularization to be successful, however, the underlying disease process needs to be halted or alleviated and there must remain a sufficient number of surviving nephron units that can serve as a scaffold for kidney regeneration. This Perspectives article describes how revascularization might be achieved using vascular growth factors or adoptive transfer of endothelial progenitor cells and provides a brief outline of the studies performed to date. An overview of how therapeutic strategies targeting the microvasculature could be enhanced in the future is also presented. PMID- 22310953 TI - Vasculitis: the elusive optimal induction strategy for vasculitis. PMID- 22310954 TI - Transplantation: the global role of kidney transplantation. PMID- 22310956 TI - Relative impact of neuromuscular and cardiovascular factors on bone strength index of the hemiparetic distal radius epiphysis among individuals with chronic stroke. AB - The objective of this study was to examine the associations of neuromuscular and cardiovascular impairments with the bone strength index of the hemiparetic distal radius epiphysis in chronic stroke survivors. The results showed that grip strength is the most predominant predictor of the bone strength index. INTRODUCTION: The purpose of the study was to examine the associations of neuromuscular and cardiovascular impairments with the bone strength index of the hemiparetic distal radius epiphysis in chronic stroke survivors. METHODS: Sixty five chronic stroke survivors and 34 healthy control subjects underwent scanning of the distal radius epiphyseal site on both sides using peripheral quantitative computed tomography to measure trabecular volumetric bone mineral density (vBMD) (mg/cm(3)), total vBMD (mg/cm(3)), total area (mm(2)), and compressive bone strength index (cBSI) (g(2)/cm(4)). Various indicators of neuromuscular (grip strength, spasticity) and cardiovascular function (vascular elasticity, oxygen consumption during 6-min walk test) were evaluated. RESULTS: Analysis of variance revealed a significant main effect of side (p < 0.001) and group * side interaction (p < 0.05) for total BMC, total vBMD, trabecular vBMD, and cBSI (p < 0.05), with the stroke group showing greater side-to-side difference in these variables. However, no significant side-to-side difference in total area was detected in either group (p > 0.05). Sex-specific analysis yielded similar results. Multiple regression analyses revealed that the cBSI of the hemiparetic distal radius epiphysis had a stronger association with neuromuscular factors than cardiovascular factors. Overall, grip strength was the strongest determinant of the cBSI of the hemiparetic distal radius epiphysis (p < 0.01). CONCLUSIONS: Muscle weakness is the most predominant determinant of cBSI in the hemiparetic distal radius epiphysis among chronic stroke patients. Future studies should investigate the efficacy of different muscle-strengthening strategies in enhancing bone strength of this skeletal site in the chronic stroke population. PMID- 22310955 TI - The multiple facets of periostin in bone metabolism. AB - Periostin is a matricellular glutamate-containing protein expressed during ontogenesis and in adult connective tissues submitted to mechanical strains including bone and, more specifically, the periosteum, periodontal ligaments, tendons, heart valves, or skin. It is also expressed in neoplastic tissues, cardiovascular and fibrotic diseases, and during wound repair. Its biological functions are extensively investigated in fields such as cardiovascular physiology or oncology. Despite its initial identification in bone, investigations of periostin functions in bone-related physiopathology are less abundant. Recently, several studies have analyzed the potential role of periostin in bone biology and suggest that periostin may be an important regulator of bone formation. The aim of this article is to provide an extensive review on the implications of periostin in bone biology and its potential use in benign and metabolic bone diseases. PMID- 22310957 TI - Burden of pelvis fracture: a population-based study of incidence, hospitalisation and mortality. AB - The objective of this study was to describe the incidence and consequences of pelvic fractures in a community cohort. The incidence of pelvic fractures increases with age with a protective effect of higher body mass index. Almost 60% of those with a pelvic fracture required an inpatient stay, with a median of 9 days. There was a higher 3-year mortality in those admitted (17%) vs. those not admitted (6.3%). Given the substantial health burden, further work is required to identify the optimal post-fracture therapeutic strategy to improve outcomes. INTRODUCTION: The burden of pelvis fractures is projected to increase, but there is a paucity of community-based studies describing rates, mortality and future fracture risk. We therefore estimated the age, gender and BMI-specific incidence of pelvis fracture in Catalonia (North-East Spain), and assessed hospital stay and mortality following fracture. METHODS: The SIDIAP(Q) database contains validated clinical information from computerised medical records of a representative sample of 30% of the population of Catalonia. We conducted a retrospective cohort study including all subjects aged >= 40 in SIDIAP(Q) and linked to the regional Hospital Admissions Database from 2007 to 2009. Pelvis fractures were ascertained using ICD-10 codes. Incidence and mortality rates were calculated. RESULTS: A total of 1,118,173 patients (582,820 women) were observed for 3 years and 1,356 had a pelvic fracture. The rate for pelvic fracture was 4.35/10,000 person-years (pyar) [95% CI 4.13-4.59] (men-2.73 [2.48-3.01]; women 5.82 [5.46-6.20]). This increased with age, peaking in those over 90 years: 29.41 [25.74-33.59]. Higher BMI was protective (HR 0.75 per SD BMI; [0.69-0.82]). Moreover, 59.1% of fractured patients were hospitalised with a median (IQR) stay of 9 (5-16) days, and after the 3-year follow-up 13.9% died (mortality rate 10.7/100 pyar [9.3-12.3]) with higher rates in those hospitalised (17.0%). CONCLUSIONS: Pelvic fractures are associated with high rates of hospitalisation and mortality. Given this, further work is required to identify the optimal post fracture therapeutic strategy to improve outcomes in this elderly patient group. PMID- 22310958 TI - Patients reject the concept of fragility fracture--a new understanding based on fracture patients' communication. AB - We examined patients' communication about fragility fractures to gain insight into why patients do not connect fractures to bone health. The term "fragility" fracture was a misnomer to patients who perceived the event as physically and emotionally traumatic. Improved communication about such fractures could facilitate awareness of bone health. INTRODUCTION: We examined patients' communication about fragility fractures to gain insight into why patients do not perceive the connection between their fracture and low bone mass. METHODS: A descriptive phenomenological (qualitative) study was conducted. During face-to face interviews, the participants described the experience of their fracture in detail and the circumstances surrounding the fracture. Data analysis was guided by Giorgi's methodology. English-speaking male and female patients aged 65+ years and "high" risk for future fracture were eligible and screened for osteoporosis through an established screening program at an urban teaching hospital. RESULTS: We recruited 30 participants (9 males, 21 females), aged 65-88, who presented with a hip (n = 11), wrist (n = 11), shoulder (n = 6), or other (n = 2) fracture. Ten of the 30 fractures occurred inside the home and the remaining fractures occurred outside the home. Sustaining a fragility fracture was perceived as a traumatic event, both physically and emotionally. In general, participants used forceful, action-oriented words and referred to hard surfaces to describe the experience. Explanations for the fracture, other than bone quality, were often reported, especially that falls were "freak" or "fluke" events. Patients who sustained a fracture under more mundane circumstances seemed more likely to perceive a connection between the fracture and their bone health. CONCLUSIONS: The term fragility fracture was a misnomer for many older adults. By reexamining how this term is communicated to fracture patients, health care providers may better facilitate patients' awareness of bone health. PMID- 22310959 TI - Does recalled dieting increase the risk of non-vertebral osteoporotic fractures? The Tromso Study. AB - The risk of non-vertebral osteoporotic fractures increased by increasing recalled amount of weight loss when dieting in women aged >= 46 years and in those with BMI < 25 kg/m(2) participating in the Tromso Study (1994/1995-2009). The increased risk was present both in women with few and several episodes of recalled dieting. INTRODUCTION: The influence of repeated dieting on bone health is uncertain. This study aims to investigate whether recalled dieting is a risk factor for non-vertebral osteoporotic fractures. METHODS: In 1994/1995 weight and height were measured in all participants aged 25-69 years in the population-based Tromso Study. Information about socioeconomic background, diseases and lifestyle factors was collected by questionnaires-including number of recalled dieting episodes and largest amount of weight loss when dieting. The participating 20,745 women and men were followed for 15 years, fractures were registered from X-ray archives and analysed by Cox's proportional hazards models. RESULTS: Among those who recalled dieting, 975 women and 364 men suffered a non-vertebral osteoporotic fracture during follow-up. Compared to women without recalled weight loss when dieting, women who reported their largest weight loss of 11 kg or more had a hazard ratio (HR) = 1.48 (95% CI 1.13-1.94) for osteoporotic fracture, adjusted for age, marital status, body mass index, height, education, physical activity, smoking, alcohol intake, history of cardiovascular disease and psychological distress. The increased risk was statistically significant only in women aged >= 46 years and in those with BMI < 25 kg/m(2). Women who recalled >= 11 dieting episodes had HR = 1.73 (CI 1.11-2.68) for osteoporotic fracture compared to those with no recalled episodes. Dieting was not associated with risk of fractures in men, but the number of fractures was low. CONCLUSIONS: The increased risk of non vertebral osteoporotic fractures by recalled dieting in women indicates that maintenance of a stable weight may have beneficial effects on fracture risk. PMID- 22310960 TI - Calorie restriction increases cerebral mitochondrial respiratory capacity in a NO*-mediated mechanism: impact on neuronal survival. AB - Calorie restriction (CR) enhances animal life span and prevents age-related diseases, including neurological decline. Recent evidence suggests that a mechanism involved in CR-induced life-span extension is NO(*)-stimulated mitochondrial biogenesis. We examine here the effects of CR on brain mitochondrial content. CR increased eNOS and nNOS and the content of mitochondrial proteins (cytochrome c oxidase, citrate synthase, and mitofusin) in the brain. Furthermore, we established an in vitro system to study the neurological effects of CR using serum extracted from animals on this diet. In cultured neurons, CR serum enhanced nNOS expression and increased levels of nitrite (a NO(*) product). CR serum also enhanced the levels of cytochrome c oxidase and increased citrate synthase activity and respiratory rates in neurons. CR serum effects were inhibited by L-NAME and mimicked by the NO(*) donor SNAP. Furthermore, both CR sera and SNAP were capable of improving neuronal survival. Overall, our results indicate that CR increases mitochondrial biogenesis in a NO(*)-mediated manner, resulting in enhanced reserve respiratory capacity and improved survival in neurons. PMID- 22310961 TI - Lack of caveolin-1 (P132L) somatic mutations in breast cancer. PMID- 22310962 TI - Copy number variations on chromosome 4q26-27 are associated with Cantu syndrome. AB - BACKGROUND: Cantu syndrome is a rare condition which is characterized clinically by hypertrichosis, cardiomegaly and bone abnormalities. Inherited hypertrichoses are very rare human disorders whose incidence has been estimated as low as 1 in 1 billion. The genetic basis of hypertrichosis is largely unknown, and currently no single gene has been directly implicated in its pathogenesis, although position effects have been reported. METHODS: We analyzed the DNA of a patient with Cantu syndrome on the Affymetrix Cytogenetics Whole-Genome 2.7M array for copy number variations (CNVs). We then performed genomic copy number quantification using qPCR, and finally we performed gene expression analysis in the hair follicle for the genes lying within and around the region of the duplication. RESULTS: We identified a 375 kb duplication on chromosome 4q26-27. The duplication region encompassed three genes, which included MYOZ2, USP53 and FABP2. MYOZ2 and USP53 are known to be highly expressed in the cardiac muscle, and we found that USP53 is expressed in the hair follicle. CONCLUSION: We propose that CNVs involving chromosome 4q26-27 may be associated with Cantu syndrome. CNVs spanning several genes may help define the molecular basis of syndromes which have unrelated clinical features. PMID- 22310963 TI - Penetration of alkali atoms throughout a graphene membrane: theoretical modeling. AB - Theoretical studies of penetration of various alkali atoms (Li, Na, Rb, Cs) throughout a graphene membrane grown on a silicon carbide substrate are reported and compared with recent experimental results. Results of first principles modeling demonstrate a rather low (about 0.8 eV) energy barrier for the formation of temporary defects in the carbon layer required for the penetration of Li at a high concentration of adatoms, a higher (about 2 eV) barrier for Na, and barriers above 4 eV for Rb and Cs. Experiments prove migration of lithium adatoms from the graphene surface to the buffer layer and SiC substrate at room temperature, sodium at 100 degrees C and impenetrability of the graphene membrane for Rb and Cs. Differences between epitaxial and free-standing graphene for the penetration of alkali ions are also discussed. PMID- 22310964 TI - Graphene electrochemical supercapacitors: the influence of oxygen functional groups. AB - We have critically compared graphene and graphene oxide as materials for utilisation as supercapacitors indicating that the former exhibits a larger capacitance over the latter which has implications for those fabricating supercapacitors. PMID- 22310965 TI - A case of IgG4-related pulmonary disease with rapid improvement. AB - We report a 72-year-old man with respiratory involvement of immunoglobulin G4 (IgG4)-related disease, who developed dry cough and shortness of breath on effort. The chest computed tomography scan image showed massive and diffuse ground-glass opacity, interlobular thickening, and bronchial wall thickening. The infiltration of IgG4-positive plasma cells in the transbronchial lung biopsy and high serum IgG4 concentrations were found. The patient was treated with 0.6 mg/kg oral prednisolone and showed rapid improvement. This is a case of IgG4-related disease in which the only complication was respiratory involvement. PMID- 22310966 TI - Utility of magnetic resonance imaging when following up sacroiliitis in enthesitis-related arthritis. PMID- 22310967 TI - Etanercept is safely used for treating psoriatic arthritis in a patient complicated with type 1 hereditary angioedema. AB - Hereditary angioedema (HAE) is a life-threatening disorder caused by deficiency or dysfunction of the C1 inhibitor protein. Patients with HAE are restricted in various medical treatments, which can induce an HAE attack. We herein report the first case of psoriatic arthritis (PSA) with type 1 HAE successfully treated with 25 mg of etanercept without HAE attack. Etanercept may represent a useful choice for treating patients with HAE accompanied by intractable PSA and rheumatoid arthritis (RA). PMID- 22310968 TI - Synthesis, magnetic properties, and STM spectroscopy of an unprecedented octanuclear chloro-bridged nickel(II) double cubane. AB - Reaction of nickel(II) chloride hexahydrate with N-n-butyldiethanolamine H(2)L (3) in the presence of LiH in anhydrous THF leads to the formation of the unique octanuclear chloro-bridged nickel(II) double cubane [({Ni(II)(4)(MU(3) OH)Cl(3)(HL)(3)}MU(2)-Cl)(2)] (4) in 57% yield. According to single crystal X-ray structure analysis, complex 4.4CH(2)Cl(2) possesses a [({Ni(4)(MU(3)-OH)(MU(3) O)(3)(OH)(3)(N)(3)(Cl)(3)}MU(2)-Cl)(2)] core and crystallizes in the monoclinic space group P2(1)/c with a = 18.292(2), b = 19.8972(5), c = 23.295(2) A, beta = 98.408(6) degrees , V = 8387.3(8) A(3), and four molecules in the unit cell. The analysis of the SQUID magnetic susceptibility data identified 4 as a weakly coupled dimer (J(1) = 14.5 K, J(2) = -0.6 K) with a ground state of S = 0, resulting from two S = 4 states of each {Ni(4)} subunits. Although complex 4 does not show an ac out-of-phase signal in a zero dc field at temperatures of 1.8 K and higher, low-temperature magnetization measurements revealed that complex 4 is a single-molecule magnet and shows hysteretic magnetization characteristics with typical temperature and sweep-rate dependencies. The eye-catching feature of complex 4 is the presence of two different blocking temperatures (0.9 K around zero field and 1.3 K at higher fields). The origin of this highly unusual behavior can be assigned to the dimer-nature of the interaction between the two S = 4 units. Furthermore STM and current imaging tunnelling spectroscopy (CITS) were performed on aggregates of 4 drop-coated on highly oriented pyrolytic graphite (HOPG) surfaces. CITS measurements show a strong contrast in the area of the nickel centers and a HOMO-LUMO gap of approximately 0.8 V. PMID- 22310969 TI - On the mechanisms underlying the depolarization block in the spiking dynamics of CA1 pyramidal neurons. AB - Under sustained input current of increasing strength neurons eventually stop firing, entering a depolarization block. This is a robust effect that is not usually explored in experiments or explicitly implemented or tested in models. However, the range of current strength needed for a depolarization block could be easily reached with a random background activity of only a few hundred excitatory synapses. Depolarization block may thus be an important property of neurons that should be better characterized in experiments and explicitly taken into account in models at all implementation scales. Here we analyze the spiking dynamics of CA1 pyramidal neuron models using the same set of ionic currents on both an accurate morphological reconstruction and on its reduction to a single compartment. The results show the specific ion channel properties and kinetics that are needed to reproduce the experimental findings, and how their interplay can drastically modulate the neuronal dynamics and the input current range leading to a depolarization block. We suggest that this can be one of the rate limiting mechanisms protecting a CA1 neuron from excessive spiking activity. PMID- 22310970 TI - Impact of antibiotic-impregnated catheters on the timing of cerebrospinal fluid infections in non-traumatic subarachnoid hemorrhage. AB - BACKGROUND: Subarachnoid hemorrhage (SAH) has been recognized as a risk factor for ventriculostomy-related infections (VRI). In addition to the hemorrhagic cerebrospinal fluid (CSF), the potential need for prolonged catheterization may contribute to the increased CSF infection rate in this population. The use of antibiotic-impregnated catheters (AIC) has effectively reduced the risk of VRI. Herein, we examined specifically the impact of systematic insertion of AIC on the timing of CSF infections in SAH patients. METHODS: Retrospective review of patients admitted between April 2006 to March 2009 with a non-traumatic SAH who required an external ventriculostomy. Only patients with AIC were included. A meningitis or ventriculitis was diagnosed according to the published criteria of the Center for Disease Control and Prevention. RESULTS: This study includes 75 patients in which 97 drains were inserted. Seven infections (7/75 = 9.3%) occurred over 1,024 drainage days (DD), resulting in a rate of 6.8 infections/1,000 DD. The mean drainage time was 15.4 days in the infected AIC group compared with 10.2 days in the non-infected AIC group. No infection occurred before day 9 of drainage and 71% (5/7) occurred after more than 2 weeks of drainage. The observed timing of infections is delayed in comparison with that reported in series using non-AIC, which typically occur prior to the 10th day of drainage. CONCLUSIONS: In the high-risk population of non-traumatic SAH, the use of AIC delays the occurrence of infection compared with that reported with non antibiotic-impregnated catheters. This may orient management strategies in SAH patients requiring a ventriculostomy. PMID- 22310971 TI - Comparison of low, multidirectional locked nailing and plating in the treatment of distal tibial metadiaphyseal fractures. AB - PURPOSE: The aim of this study was to compare the results of a new technique for low, multidirectional locked nailing with closed reduction and minimally invasive plating in the treatment of distal tibial metadiaphyseal fractures. METHODS: Forty-six matched patients were divided according to age, gender, Injury Severity Score, and fracture pattern into group A (expert tibial nailing) and group B (minimally invasive plating). Then, the patients were followed up, and the clinical and radiographic results were retrospectively analysed. RESULTS: The mean followed-up was 24.7+/-2.7 months in group A and 25.8+/-2.8 months in group B. No patient had nonunion, shortening, hardware breakdown, or deep-seated infection. Patients in group A had a significantly shorter mean operating time, hospital stay, full weight-bearing time and union time (76+/-16.6 vs. 90+/-20.3 minutes, p=0.000; 5.8+/-2.1 vs. 8.9+/-3.1 days, p=0.000; 9.0+/-1.4 vs. 11.1+/-1.7 weeks, p=0.000; and 21.3+/-3.5 vs. 23.1+/-3.6 weeks, p=0.047, respectively). Three patients in group A and one patient in group B presented with malalignment (p=0.608). The mean Olerud-Molander Ankle score was 89.0+/-7.1 in group A and 87.6+/-8.4 in group B (p=0.478). CONCLUSIONS: Distal tibia metadiaphyseal fractures may be treated successfully with low, multidirectional locked nails or plates. However, low, multidirectional locked nailing may represent a superior surgical option, since it offers advantages in terms of mean operating time, hospital stay, full weight-bearing time and union time. PMID- 22310973 TI - Management of small renal masses: watch, cut, freeze, or fry? PMID- 22310972 TI - Can a high acromion index predict rotator cuff tears? AB - PURPOSE: The purpose of this study was to identify the relationship between an acromion index (AI) and the size of a rotator cuff tear. The hypothesis of our study was that an AI will be higher in patients with a full-thickness tear than in patients with a partial-thickness articular-side tear, and that it can be used as a predictor for the size of a rotator cuff tear. METHODS: We included 284 patients who had been diagnosed with rotator cuff tears and had undergone arthroscopic rotator cuff repair at our institute. All patients were divided into five distinct groups (partial-thickness articular side tear, and four subgroups of full-thickness tears) depending on the size of the rotator cuff tear on arthroscopy. In each patient, an AI was measured on the pre-operative oblique coronal MR images and then analysed to determine the difference between groups. RESULTS: There were statistically significant differences between the partial thickness articular side rotator cuff tear and large-to-massive rotator cuff tear groups (p < 0.01), and the mean value of an AI was highest in the large-sized full-thickness tear group. The AI of the partial-thickness articular-side rotator cuff tear group was statistically different from the large-to-massive rotator cuff tear groups. CONCLUSIONS: The AI can be a predictor which can differentiate a partial-thickness articular-side tear and a large-to-massive rotator cuff tear pre-operatively. However the AI could not provide useful guidance on predicting the differences in tear size in full-thickness tear patients. We suggest that a high AI can be one of the associated factors for progression to large-to-massive rotator cuff tears in a rotator cuff disease. PMID- 22310974 TI - Modified PNA-PCR method: a convenient and accurate method to screen plasma KRAS mutations of cancer patients. AB - KRAS mutations are proved to confer dramatic resistance to EGFR target therapy of cancer patients. The aim of this study was to establish a convenient and accurate method to screen plasma KRAS mutations of cancer patients since tumor specimens were not always available in clinical practice. A modified PNA-PCR method was established and evaluated in plasma of 19 pancreatic cancer patients. Our results showed that the modified PNA-PCR assay was a sensitive (87.5%, 14/16) and accurate (92.9%, 13/14) method to screen plasma KRAS mutations of pancreatic cancer patients and there was a high consistency of KRAS mutation status between plasma samples and tumor specimens. The modified protocol could not only screen plasma KRAS mutations rapidly and accurately but also had potential to quantify KRAS mutant DNA to predict treatment response of cancer patients and monitor disease progression. It's should be indicated that this modified assay was only confirmed in the pancreatic cancer patients in this study and need to be verified in other cancer patients. PMID- 22310975 TI - Secreted CLU is associated with the initiation of triple-negative breast cancer. AB - Triple-negative breast cancer, which is negative for the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, represents about 15-26% of all breast cancer cases. However, because of its genotype, a triple-negative disease accounts for a remarkable metastasis and mortality. Moreover, no targeted treatment is available because the molecular mechanism of triple-negative breast cancer initiation is still unclear. Secreted clusterin (sCLU) is associated with the refractory to anti-estrogen in breast cancer cells. We investigated the sCLU expression in 384 human breast cancer cases, including 61 triple-negative cases, as well as the relationship between sCLU and clinical pathological characteristics. Triple-negative patients (75.4%) were positive for sCLU based on immunohistochemical analysis, and sCLU expression in this subtype was proven related to a larger tumor size, an axillary node status, and a higher clinical stage. Furthermore, we used a spontaneous breast cancer mouse strain with a triple-negative genotype to detect the sCLU dynamic expression in breast cancer oncogenesis using western blot and real-time polymerase chain reaction. The sCLU mRNA and protein expression in the tumor and hyperplastic epithelium were upregulated and reached a peak compared with those of a normal mammary gland. These results suggest that sCLU is involved in the initiation of triple negative breast cancer, which is beneficial for the clinical trial design of an anti-CLU treatment for triple-negative breast cancer. PMID- 22310976 TI - MiR-135a targets JAK2 and inhibits gastric cancer cell proliferation. AB - The role of tumor suppressors and cell cycle factors in gastric carcinogenesis are well understood; however, the post-transcriptional changes that affect gene expression in gastric cancer are poorly characterized. MiR-135a has been shown to play a role in Hodgkin lymphoma. The aim of this study was to investigate the expression and role of miR-135a in gastric cancer. Quantitative real-time PCR demonstrated that miR-135a expression is downregulated in the majority of human primary gastric cancer tissues (8/11; 73%), compared with pair-matched adjacent non-tumor tissues. Furthermore, compared with the nonmalignant gastric cell line, GES-1, miR-135a expression was substantially downregulated in gastric cancer cell lines of various degrees of differentiation. Target analysis indicated miR-135a directly regulates Janus kinase 2 (JAK2), a cytoplasmic tyrosine kinase involved in cytokine receptor signaling pathways. Overexpression of miR-135a significantly downregulated the expression of JAK2 protein and also reduced gastric cancer cell proliferation and colony formation in vitro. MiR-135a-mediated JAK2 downregulation also reduced p-STAT3 activation and cyclin D1 and Bcl-xL protein expression. This study suggests that miR-135a may function as a tumor suppressor via targeting JAK to repress p-STAT3 activation, reduce cyclin D1 and Bcl-xL expression and inhibit gastric cancer cell proliferation. These results imply that novel treatment approaches targeting miR-135a may potentially benefit patients with gastric cancer. PMID- 22310977 TI - CIP2A overexpression is associated with c-Myc expression in colorectal cancer. AB - BACKGROUND: To improve the prognostic evaluation of colorectal cancer requires new molecular markers. Cancerous inhibitor of protein phosphatase 2A (CIP2A) serves as an oncoprotein by targeting PP 2A-mediated inhibition of c-Myc. A prognostic role for CIP2A has been demonstrated in gastric, lung and tongue cancers. RESULTS: CIP2A was overexpressed in 661 (87.9%) specimens. CIP2A overexpression was associated with tumor differentiation grade (p = 0.014), p53 immunopositivity (p = 0.042), EGFR immunopositivity (p = 0.007) and c-Myc nuclear immunopositivity (p = 0.018). In survival analysis, CIP2A failed to show any prognostic significance (p = 0.270, log-rank test). METHODS: 863 consecutive colorectal cancer patients treated at Helsinki University Central Hospital in 1983-2001 were collected with 752 scored successfully for CIP2A immunohistochemical expression from tumor tissue microarrays. Associations with clinicopathologic variables and molecular markers were explored by the chi-square test, and the Kaplan-Meier method served for survival analysis. CONCLUSIONS: Overexpression of CIP2A in colorectal cancer patients may be an important step in colorectal carcinogenesis. Based on our findings, CIP2A shows no association with patient prognosis in colorectal cancer, but is associated with nuclear c-Myc. PMID- 22310978 TI - Polymorphisms in genes involved in drug detoxification and clinical outcomes of anthracycline-based neoadjuvant chemotherapy in Chinese Han breast cancer patients. AB - BACKGROUND: The large individual variability for anticancer drugs in both outcome and toxicity risk makes the identification of pharmacogenetic markers that can be used to screen patients before therapy selection an attractive prospect. AIMS: This work aimed to evaluate the importance of genetic polymorphisms involved in drug detoxification to predict clinical outcomes of anthracycline-based neoadjuvant chemotherapy for breast cancer. RESULTS: GSTP1 313 AA genotype was associated with a poor clinical response relative to G allele carrier (58.4% vs 80.8%; p = 0.006), and MDR1 3435 TT genotype had a worse response compared with C allele carrier (33.3% vs 71.2% p = 0.001). Patients with both the adverse genotypes of GSTP1 314AA and MDR 3435TT showed the worst therapy efficacy in all (14.3%; p = 0.000). Kaplan-Meier survival analysis showed that the patients with no adverse genotype were associated with decreased hazard of relapse (p = 0.002), compared with those with 1 or 2 adverse genotypes. Multivariate analysis demonstrated that clinical response and no adverse genotype was independent predictors of disease-free survival (DFS). METHODS: Genotyping was performed by allele-specific oligonucleotide ligation reaction (MnSOD, CAT, GSTP1), multiplex PCR (GSTM1, GSTT1) or PCR-RFLP (MDR1). Based on 153 patients received anthracycline-based neoadjuvant chemotherapy, these genotypes or their combinations in relation to treatment-related response, hematologic toxicity and DFS were investigated. CONCLUSIONS: These results suggest that polymorphisms in GSTP1 and MDR1 may help to predict clinical response and DFS of anthracycline based chemotherapy, and a polygenic pathway approach should provide more useful information. The findings required independent prospective confirmation. PMID- 22310979 TI - Impact of different treatment of whole-body cryotherapy on circulatory parameters. AB - Cryotherapy is commonly used as a procedure to relieve pain symptoms, particularly in inflammatory diseases, injuries and overuse symptoms. A peculiar form of cold therapy or stimulation was proposed 30 years ago for the treatment of rheumatic diseases. The therapy consists in the exposure to very cold air in special cryochambers. The air is maintained at temperatures between -110 and -160 degrees C. The treatment was named whole-body cryotherapy (WBC). It consists in a brief exposure to extreme cold in a temperature-controlled chamber. It is applied to relieve pain and inflammatory symptoms caused by numerous disorders, particularly those associated with rheumatic conditions, and it is recommended for the treatment of arthritis, fibromyalgia and ankylosing spondylitis. The aim of this study was to investigate the effects of different treatment of WBC on blood pressure (BP) and heart rate (HR) parameters in adult subjects characterized from non-pathological values of BP. Eighty subjects (36 females, 44 males, age range 19-80 years) submitted to 4-17 WBC applications for a total of 816 treatments were recruited. Immediately before and after each WBC application systolic and diastolic BP and HR were measured and recorded. We did not find significant differences in BP and HR (p > 0.05). WBC seems to be safe with respect to unwanted BP and HR alterations for adult patients. An individual monitoring of subjects is recommended over the treatment, but pathological changes of circulatory parameters can be considered rare and occasional. PMID- 22310980 TI - Cardiac magnetic resonance derived late microvascular obstruction assessment post ST-segment elevation myocardial infarction is the best predictor of left ventricular function: a comparison of angiographic and cardiac magnetic resonance derived measurements. AB - Microvascular obstruction (MVO) is a strong independent predictor of left ventricular remodelling and mortality following ST-segment elevation myocardial infarction (STEMI). Microvascular obstruction can be identified at angiography or with gadolinium-enhanced cardiac MRI (CMR). First-pass perfusion CMR also allows a novel quantitative evaluation of myocardial blood flow (MBF) that might provide superior predictive data in the assessment of MVO. We sought to compare angiographic and CMR derived methodologies in the assessment of MVO to determine the optimal methodology that best predicts the surrogate outcome marker of left ventricular function post STEMI. Following primary-PCI angiographic assessment of 'no-reflow' with TIMI myocardial perfusion grade (TMPG) and myocardial blush grade (MBG) were documented. Assessment of CMR derived MVO was assessed on day 3, with MVO on first-pass perfusion imaging termed 'early MVO' and on late gadolinium enhancement, 'late MVO'. Furthermore on the same day 3 CMR scan, myocardial blood flow in the infarct region was quantified at adenosine stress and rest utilizing standard perfusion imaging sequences. Assessment of remodelling, structure and function was undertaken via standard CMR imaging assessment on day 90 post-STEMI and was used as the surrogate marker for long term clinical outcome. Forty patients (age 59 +/- 12 years, 84% males) were appraised. Late MVO had the strongest correlation with LVEF at 90 days compared to the CMR parameters of early MVO, stress infarct region MBF and rest infarct region MBF (r = -0.754, r = -0.588, r = 0.595 and r = 0.345 respectively). Of the angiographic parameters used to assess MVO, TMPG had the strongest relationship with MVO when assessed via CMR. Myocardial blush grade however showed no relationship to CMR derived assessment of MVO. On multivariate analysis, of all angiographic and CMR variables, late MVO was the strongest predictor of LVEF at 90 days (p = 0.004). Cardiac magnetic resonance imaging derived assessment of microvascular obstruction on late gadolinium enhancement strongly predicts left ventricular function following STEMI at 90 days. PMID- 22310981 TI - Assessment of right ventricular function by three-dimensional echocardiography and myocardial strain imaging in adult atrial septal defect before and after percutaneous closure. AB - Real-time three-dimensional (3D) echocardiography allows us to measure right ventricular (RV) end-diastolic volume irrespective of its shape. Tissue Doppler imaging (TDI) and speckle tracking imaging (STI) are new tools to assess myocardial function. We sought to evaluate RV function by 3D echocardiography and myocardial strain imaging in adult patients with atrial septal defect (ASD) before and 6 months after transcatheter closure in order to assess the utility of these new indexes in comparison with standard two-dimensional (2D) and Doppler parameters. Thirty-nine ASD patients and 39 healthy age- and sex-matched controls were studied using a commercially available cardiovascular ultrasound system. 2D Doppler parameters of RV function (fractional area change, tricuspid annular plane systolic excursion, myocardial performance index) were calculated. 3D RV volumes were also obtained. RV peak-systolic velocities, peak-systolic strain, and peak systolic and diastolic strain-rate were measured in the basal, mid and apical segments of lateral and septal walls in apical 4-chamber view by TDI and STI. In open ASD, RV ejection fraction (3D-RVEF) and global and regional RV longitudinal strain were significantly higher than control group and decreased significantly after closure. By multivariate analysis 3D-RVEF, apical strain and strain rate were independent predictors of functional class. ROC analysis showed 3D-RVEF and apical strain to be more sensitive predictors of unfavorable outcome after defect closure compared to 2D-Doppler indexes. 3D echocardiography and myocardial strain imaging give useful insights in the quantitative assessment of RV function in ASD patients before and after closure. PMID- 22310982 TI - Different susceptibility of rat pancreatic alpha and beta cells to hypoxia. AB - Insulin-producing beta cells are known to be highly susceptible to hypoxia, which is a major factor in their destruction after pancreatic islet transplantation. However, whether the glucagon-producing pancreatic islet alpha cells are sensitive to hypoxia is not known. Our objective was to compare the sensitivity of alpha and beta cells to hypoxia. Isolated rat pancreatic islets were exposed to hypoxia (1% oxygen, 94% N(2), 5% CO(2)) for 3 days. The viability of the alpha and beta cells, as well as the stimulus-specific secretion of glucagon and insulin, was evaluated. A quantitative analysis of the proportion of beta to alpha cells indicated that, under normoxic conditions, islet cells were composed mainly of beta cells (87 +/- 3%) with only 13 +/- 3% alpha cells. Instead, hypoxia treatment significantly increased the proportion of alpha cells (40 +/- 13%) and decreased the proportion of beta cells to 60 +/- 13%. Using the fluorescent TUNEL assay we found that only a few percent of beta cells and alpha cells were apoptotic in normoxia. In contrast, hypoxia induced an abundance of apoptotic beta cells (61 +/- 22%) and had no effect on the level of apoptosis in alpha cells. In conclusion, this study demonstrates that hypoxia results in severe functional abnormality in both beta and alpha cells while alpha cells display significantly decreased rate of apoptosis compared to intensive apoptotic injury of beta cells. These findings have implications for the understanding of the possible role of hypoxia in the pathophysiology of diabetes. PMID- 22310983 TI - Guanylin and functional coupling proteins in the hepatobiliary system of rat and guinea pig. AB - Guanylin, a bioactive intestinal peptide, is involved in the cystic fibrosis transmembrane conductance (CFTR)-regulated electrolyte/water secretion in various epithelia. In the present work we report on the expression and cellular localization of guanylin and its affiliated signaling and effector proteins, including guanylate cyclase C (Gucy2c), Proteinkinase GII (Pkrg2), CFTR and the solute carrier family 4, anion exchanger, member 2 (Slc4a2) in the hepatobiliary system of rat and guinea pig. Localization studies in the liver and the gallbladder revealed that guanylin is located in the secretory epithelial cells of bile ducts of the liver and of the gallbladder, while Gucy2c, Pkrg2, CFTR, and Slc4a2 are confined exclusively to the apical membrane of the same epithelial cells. Based on these findings, we assume that guanylin is synthesized as an intrinsic peptide in epithelial cells of the hepatobiliary system and released luminally into the hepatic and cystic bile to regulate electrolyte secretion by a paracrine/luminocrine signaling pathway. PMID- 22310984 TI - Pinch-1 was up-regulated in leukemia BMSC and its possible effect. AB - Pinch-1, a widely expressed focal adhesion protein, has been demonstrated to be up-regulated in multiple solid tumor-associated stromal cells, particularly at invasive edges. It was supposed that Pinch-1 was intimately associated with development and progression of tumors. The expression of Pinch-1 in hematopoietic microenvironment in patients with leukemia remains unclear. This study focused on the expression of Pinch-1 in bone marrow stromal cells (BMSCs) from leukemia patients and its possible effect. BMSC was isolated and cultured from bone marrow in leukemia patients and normal healthy donors. RT-PCR and Western blot analysis were performed to determine Pinch-1 mRNA and protein level in BMSC, respectively. Lentiviral vector containing Pinch-1 siRNA was constructed, and the recombinant lentivirus particle was packaged in 293 cells. Effectiveness of Pinch-1 siRNA was determined by Western blot. The proliferation, apoptosis and motility of leukemia BMSC subjected to Pinch-1 knockdown using siRNA were tested by flow cytometry, TUNEL assay and Transwell system, respectively. Pinch-1 mRNA and protein were significantly up-regulated in ALL and AML BMSC compared to normal BMSC (p<0.01). Although there was no difference in Pinch-1 mRNA between ALL and AML BMSC, cellular levels of Pinch-1 protein in ALL BMSC were significantly higher than that in AML BMSC (p<0.01). Overexpressed Pinch-1 was significantly reduced in leukemia BMSC transfected with Pinch-1 siRNA evidenced by Western blot. Flow cytometry analysis showed that the percentage of cells in S+G2 phases in leukemia BMSC transfected with Pinch-1 siRNA was significantly lower than control (p<0.01). The percentage of apoptotic cells in leukemia BMSC transfected with Pinch-1 siRNA was 19.8+/-1.0%, significantly higher than controls (p<0.01). The number of leukemia BMSC transfected with Pinch-1 siRNA that migrated to the lower chamber after culturing for 24 h was 8.4+/-1.1 per field, significantly lower than controls (p<0.01). Pinch-1 mRNA and protein in leukemia BMSC were up regulated drastically compared with BMSC from healthy donors. Leukemia BMSC displayed hypoproliferation, decreased migration and increased apoptosis after transfecting Pinch-1 siRNA. PMID- 22310985 TI - Efficacy and safety of limbal-conjunctival autografting with limbal fixation sutures after pterygium excision. AB - PURPOSE: To evaluate the efficacy and safety of limbal-conjunctival autografting with limbal fixation sutures after pterygium excision. METHODS: We retrospectively reviewed the records of 90 patients (103 eyes) who received limbal-conjunctival autografts with limbal fixation sutures after excision of the primary pterygium (82 eyes) and recurrent pterygium (21 eyes). RESULTS: The study subjects comprised 41 male patients (47 eyes) and 49 female patients (56 eyes) with a mean age of 51.1 +/- 10.5 years (range 32-77). The mean follow-up period was 18.9 +/- 9.2 months (range 12-50). Among the 103 eyes, recurrence occurred in 2 eyes (1.9%) after 2 and 4 months, respectively. As complications, 1 case of conjunctival cyst and 2 cases of pseudopterygium at the donor site were reported. CONCLUSIONS: Limbal-conjunctival autografting with limbal fixation sutures appears to be an effective and safe method of reducing the recurrence rate after pterygium excision. PMID- 22310989 TI - Neuromuscular disease. A novel imaging method to quantify low levels of dystrophin in Duchenne muscular dystrophy. PMID- 22310991 TI - Forming trifluoromethylmetallates: competition between decarboxylation and C-F bond activation of group 11 trifluoroacetate complexes, [CF3CO2ML]-. AB - A combination of gas-phase 3D quadrupole ion trap mass spectrometry experiments and density functional theory (DFT) calculations have been used to examine the mechanism of thermal decomposition of fluorinated coinage metal carboxylates. The precursor anions, [CF(3)CO(2)MO(2)CCF(3)](-) (M = Cu, Ag and Au), were introduced into the gas-phase via electrospray ionization. Multistage mass spectrometry (MS(n)) experiments were conducted utilizing collision-induced dissociation, yielding a series of trifluoromethylated organometallic species and fluorides via the loss of CO(2), CF(2) or "CF(2)CO(2)". Carboxylate ligand loss was insignificant or absent in all cases. DFT calculations were carried out on a range of potentially competing fragmentation pathways for [CF(3)CO(2)MO(2)CCF(3)](-), [CF(3)CO(2)MCF(3)](-) and [CF(3)CO(2)MF](-). These shed light on possible products and mechanisms for loss of "CF(2)CO(2)", namely, concerted or step-wise loss of CO(2) and CF(2) and a CF(2)CO(2) lactone pathway. The lactone pathway was found to be higher in energy in all cases. In addition, the possibility of forming [CF(3)MCF(3)](-) and [CF(3)MF](-), via decarboxylation is discussed. For the first time the novel fluoride complexes [FMF](-), M = Cu, Ag and Au have been experimentally observed. Finally, the decomposition reactions of [CF(3)CO(2)ML](-) (where L = CF(3) and CF(3)CO(2)) and [CH(3)CO(2)ML](-) (where L = CH(3) and CH(3)CO(2)) are compared. PMID- 22310992 TI - Unconventional 0-, 1-, and 2-dimensional single-crystalline copper sulfide nanostructures. AB - We report the synthesis of several unconventional 0-, 1- and 2-dimensional copper sulfide nanostrucutures by the chemical vapor deposition method. The key factor for morphology and structure control of a variety of copper sulfide products is the tuning of deposition and growth temperature to fit for the surface energy barriers and promote different growth directions. At a high growth temperature (480 degrees C) that provides enough thermal energy, a 0-D octahedral copper sulfide single crystal structure was synthesized. At a slightly lower growth temperature (460 degrees C), a new 1-D copper sulfide nanorod structure with a nanocrystal head was discovered for the first time. At a much lower growth temperature (150 degrees C), 2-D copper sulfide nanoflakes with a single crystal hexagonal structure were obtained. These novel structural varieties of copper sulfide can lead to discovering more unconventional material structures and growth mechanisms of other transitional metal chalcogenides, and may allow for new copper sulfide based devices and applications. PMID- 22310993 TI - How free healthcare became mired in corruption and murder in a key Indian state. PMID- 22310994 TI - New evidence of worse outcomes for weekend patients reignites call for seven day hospital services. PMID- 22310995 TI - Death toll from malaria is double the WHO estimate, study finds. PMID- 22310996 TI - Whole genome sequencing and biological characterization of Duck/JS/10, a new lentogenic class I Newcastle disease virus. AB - A lentogenic Newcastle disease virus (NDV), Duck/JS/10 (JS10), was isolated from an unvaccinated duck in China. The complete genome of the virus contained 15,198 nucleotides. Based on length of the genome and a partial sequence of the F gene, the virus was classified as a class I genotype 4 NDV. The antigenicity of the virus was compared with that of NDV strain La Sota via hemagglutination inhibition (HI), virus neutralization (VN) assay and animal experiments. Our results show that JS10 generates higher HI and VN titers than La Sota against both class I and II virulent NDV strains. Experiments on animals demonstrate that virus shedding from chickens vaccinated with JS10 is significantly reduced when compared to those vaccinated with La Sota. Overall, this study strongly suggests that JS10 may qualify as a new vaccine candidate against Newcastle disease. PMID- 22310997 TI - A clinical analysis on microvascular decompression surgery in a series of 3000 cases. AB - OBJECTIVE: Despite the microvascular decompression (MVD) has become a definitive treatment for trigeminal neuralgia (TN) and hemifacial spasm (HFS), not all of the patients have been cured completely so far and this sort of operation is still with risk because of the critical operative area. In order to refine this surgery, we investigated thousands MVDs. METHODS: Among 3000 consecutive cases of MVDs have been performed in our department, 2601 were those with typical TN or HFS, who were then enrolled in this investigation. They were retrospectively analyzed with emphasis on the correlation between surgical findings and postoperative outcomes. The differences between TN and HFS cases were compared. The strategy of each surgical process of MVD was addressed. RESULTS: Postoperatively, the pain free or spasm cease occurred immediately in 88.3%. The symptoms improved at some degree in 7.2%. The symptoms unimproved at all in 4.5%. Most of those with poor outcome underwent a redo MVD in the following days. Eventually, their symptoms were then improved in 98.7% of the reoperative patients. The majority reason of the failed surgery was that the neurovascular conflict located beyond REZ or the offending veins were missed for TN, while the exact offending artery (arteriole) was missed for HFS as it located far more medially than expected. CONCLUSION: A prompt recognition of the conflict site leads to a successful MVD. To facilitate the approach, the craniotomy should be lateral enough to the sigmoid sinus. The whole intracranial nerve root should be examined and veins or arterioles should not be ignored. For TN, all the vessels contacting the nerve should be detached. For HFS, the exposure should be medial enough to the pontomedullary sulcus. PMID- 22310998 TI - Medical information on the Internet: Quality assessment of lumbar puncture and neuroaxial block techniques on YouTube. AB - BACKGROUND: The Internet has become the largest, most up-to-date source for medical information. Besides enhancing patients' knowledge, the freely accessible audio-visual files have an impact on medical education. However little is known about their characteristics. In this manuscript the quality of lumbar puncture (LP) and spinal anaesthesia (SA) videos available on YouTube is assessed. METHODS: This retrospective analysis was based on a search for LP and SA on YouTube. Videos were evaluated using essential key points (5 in SA, 4 in LP) and 3 safety indicators. Furthermore, violation of sterile working techniques and a rating whether the video must be regarded as dangerously misleading was performed. RESULTS: From 2321 hits matching the keywords, 38 videos were eligible for evaluation. In LP videos, 14% contained information on all, 4.5% on 3 and 4.5% on 2 key points, 59% on 1 and 18% on no key point. Regarding SA, no video contained information on all 5 key points, 56% on 2-4 and 25% on 1 key point, 19% did not contain any essential information. A sterility violation occurred in 11%, and 13% were classified as dangerously misleading. CONCLUSIONS: Even though high quality videos are available, the quality of video clips is generally low. The fraction of videos that were not performed in an aseptic manner is low, but these pose a substantial risk to patients. Consequently, more high-quality, institutional medical learning videos must be made available in the light of the increased utilization on the Internet. PMID- 22310999 TI - Neurophysiological characterization of the 'new anatomy' and motor control that results from neurological injury or disease. AB - Following injury or disease, the central nervous system (CNS), to varying degrees, loses neurons, synaptic connections and conduction-promoting myelin insulation altering the neural circuitry assembled during development. This "New Anatomy" changes neural processing, bringing spasticity, paresis and paralysis to motor function and altered sensation, numbness and pain to sensory function. Focusing on the effects of CNS damage on the motor subsystems, this review offers a neurophysiological assessment perspective developed within the study of human spinal cord injury and extends it to other CNS disorders. It puts forward the concept that there are essential domains of CNS processing, altered by most neurological disorders, that are temporal, the speed of activation and deactivation, and spatial, the distribution across multiple muscles of motor units selected and activated. Measured through multiple-muscle recordings of selected motor-task performance, these domains can be useful in quantifying the severity of CNS damage and changes achieved through recovery or treatment. PMID- 22311000 TI - Reduction of shunt obstructions by using a peel-away sheath technique? A multicenter prospective randomized trial. AB - OBJECTIVE: Shunt obstructions may partly be caused by brain debris, which intrude into the ventricular catheter during ventricle puncture. Avoiding contact between the catheter and brain tissue, by using a peel-away sheath, should reduce the number of shunt failures caused by obstruction. To test this hypothesis, we conducted a randomized, prospective multicenter study. METHODS: 201 patients from 6 different neurosurgical centers in Germany receiving a ventriculo-peritoneal shunt were included in this study. Of these, 177 patients completed a 1-year follow-up period. Surgery was randomized in a 1 to 1 fashion, such that out of 177 procedures, 91 were performed using a peel-away sheath and 86 were performed without. The rate of surgical re-interventions and shunt obstructions within a 12 month period was recorded. RESULTS: Within 1 year post-surgery, 17 shunt obstructions (9.6%) leading to shunt revisions were recorded. However, no difference was found between surgeries performed using a peel-away sheath (9.9%) or not (9.3%). The overall shunt infection rate was 2.8% and the shunt revision rate for overdrainage was 3.9%. CONCLUSIONS: The theoretical advantages attributed to the use of a peel-away sheath to introduce a ventricular catheter could not be confirmed in this randomized study, suggesting that the proposed role of brain debris in shunt obstructions may be overestimated. PMID- 22311001 TI - Gastro-enteritis in hypokalemic periodic paralysis: a life threatening condition. PMID- 22311002 TI - Cation-responsive silver-selective organogel-exploiting silver-alkene interactions in the gel-phase. AB - We report a gelator that is responsive to Ag(+) and Li(+) cations but unresponsive to Na(+) and K(+), and demonstrate that silver-alkene interactions play a vital role in mediating the selective gel-sol response to Ag(+). PMID- 22311003 TI - Three-dimensional circumferential liposuction of the overweight or obese upper arm. AB - Due to recent trends in liposuction, anatomic consideration of the body's fatty layers is essential. Based on this knowledge, a circumferential approach to achieving maximal aesthetic results is highlighted. In the upper arm, aspiration of fat from only the posterolateral region can result in skin flaccidity and disharmony of the overall balance of the upper arm contour. Different suction techniques were applied depending on the degree of fat accumulation. If necessary, the operation area was extended around the axillary and scapular regions to overcome the limitations of the traditional method and to achieve optimal effects. To maximize skin contracture and redraping, the authors developed three-dimensional circumferential liposuction (3D-CL) based on two concepts: circumferential aspiration of the upper arm, to which was applied different fluid infiltration and liposuction techniques in three anatomic compartments (anteromedial, anterolateral, and posterolateral), and extension of liposuction to the periaxillar and parascarpular areas. A total of 57 female patients underwent liposuction of their excess arm fat using this technique. The authors achieved their aesthetic goals of a straightened inferior brachial border and a more slender body contour. Complications occurred for five patients including irregularity, incision-site scar, and transient pigmentation. Through 3D-CL, the limitations of traditional upper arm liposuction were overcome, and a slender arm contour with a straightened inferior brachial border was produced. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at http://www.springer.com/00266. PMID- 22311004 TI - Antihypertensive response to thiazide diuretic or angiotensin receptor blocker in elderly hypertensives is not influenced by pretreatment plasma renin activity. AB - PURPOSE: Renin profiling has been proposed as a method to guide antihypertensive drug selection. This prespecified post-hoc analysis examined the influence of baseline plasma renin activity (PRA) on blood pressure (BP) responses. METHODS: A 16-week, randomized, double-blind, prompted-titration trial evaluated initial valsartan (V)/hydrochlorothiazide (HCTZ) combination therapy versus initial HCTZ or V monotherapy in individuals aged >= 70 years with systolic hypertension. Sitting PRA was measured at baseline, Week 4, and Week 16. Subjects were stratified into 2 groups for analysis: low renin (baseline PRA < 0.65 ng/mL/h) or normal-high renin (baseline PRA >= 0.65 ng/mL/h). RESULTS: PRA data were available in 322/384 subjects: 178 had low PRA and 144 had normal-high PRA. At Week 4, V/HCTZ was more effective than HCTZ or V at reducing mean sitting systolic BP (MSSBP), independent of baseline PRA, with reductions of -16.9, 12.6, and -9.5 mmHg, respectively, in low-renin subjects and -19.4, -11.5, and 8.6 mmHg in normal-high renin subjects. Baseline PRA was similar in responders (subjects not uptitrated at Week 4) and nonresponders (subjects uptitrated at Week 4). In responders, the reactive rise in PRA at Week 4 was related to change in MSSBP, with the greatest increases in PRA observed in the V/HCTZ group. Higher baseline PRA was associated with a greater reactive rise in PRA. CONCLUSIONS: Baseline PRA is not a useful guide to the BP responses of initial combination V/HCTZ in elderly individuals with systolic hypertension. PMID- 22311005 TI - Visualization of auxin-mediated transcriptional activation using a common auxin responsive reporter system in the liverwort Marchantia polymorpha. AB - The phytohormone auxin plays a pivotal role in various developmental aspects in land plants. However, little is known of the auxin response and distribution in non-vascular plants. In this study, we made transgenic plants of the liverwort Marchantia polymorpha which express the uidA (GUS) reporter gene under control of the soybean auxin-inducible promoter, ProGH3, and used it to indirectly monitor auxin-mediated transcriptional activation in planta. Transgenic plants carrying ProGH3:GUS showed GUS activity in an auxin-dependent manner. Histochemical GUS staining was observed at the bottom of gemma cups in the process of vegetative propagation. Significant GUS activity was also detected around the gametophyte sporophyte junction as well as the developing sporophyte after fertilization. These results suggest that the activity of auxin is crucial in both gametophyte and sporophyte development in M. polymorpha, and that the mechanism for auxin mediated transcriptional activation had already been established when plants emerged on the terrestrial environment. PMID- 22311006 TI - Experimental exposure of healthy subjects with emissions from a gas metal arc welding process--part II: biomonitoring of chromium and nickel. AB - OBJECTIVES: The objective of this study was to investigate whether there is a relationship between the external exposure dose of chromium and nickel caused by a metal active gas welding process with a solid high-alloyed steel welding wire and inner exposure of subjects. In order to perform welding fume exposure under controlled and standardized conditions, the investigations were conducted in the "Aachen Workplace Simulation Laboratory". METHODS: To perform biological monitoring of chromium and nickel, blood and urine samples of 12 healthy male non smokers who never worked as welders were collected before and after a 6-h exposure to ambient air (0 mg/m(3)) and to welding fumes of a metal active gas welding process once with a concentration of the welding fume of 1 mg/m(3) and once with a concentration of 2.5 mg/m(3). RESULTS: Although the internal exposure to chromium and nickel in this study was comparatively low, the subjects showed significantly increased concentrations of these metals in urine after exposure to welding fume compared to the values at baseline. Moreover, the observed increase was significantly dose dependent for both of the substances. CONCLUSION: For the biological monitoring of chromium and nickel in urine of subjects exposed to welding fumes, a dependency on exposure dose was seen under standardized conditions after a single exposure over a period of 6 h. Thus, this study contributes to a better understanding of the relationship between ambient and biological exposures from welding fumes and provides a good basis for evaluating future biological threshold values for these metals in welding occupation. PMID- 22311007 TI - Exposure of healthy subjects with emissions from a gas metal arc welding process: part 1--exposure technique and external exposure. AB - BACKGROUND: Studies concerning welding fume-related adverse health effects in welders are hampered by the heterogeneity of workplace situations, resulting in complex and non-standardized exposure conditions. METHODS: In order to carry out welding fume exposure studies under controlled and standardized conditions, the Aachen Workplace Simulation Laboratory was developed. This laboratory consists of an emission room, in which welding fume is produced, and an exposure room in which human subjects are exposed to these fumes. Both rooms are connected by a ventilation system which allows the welding fume concentration to be regulated. Particle mass concentration was measured with a TEOM microbalance and the particle number-size distribution using a Grimm SMPS device. RESULTS: In a study, which is the subject of this paper, it has been shown that welding fume concentration can easily be regulated between 1 and about 3 mg m(-3). The chosen concentration can be kept constant for more than 8 h. However, transport of the particles from the emission room into the exposure room leads to a change in particle size distribution, which is probably due to coagulation of the fraction of smallest particles. CONCLUSION: The Aachen Workplace Simulation Laboratory is suitable for controlled exposure studies with human subjects. PMID- 22311008 TI - Exposure of healthy subjects with emissions from a gas metal arc welding process: part 3--biological effect markers and lung function. AB - BACKGROUND: Metal active gas welding (MAG) is a widely-used welding technique resulting in high emissions of welding fume particles. This study investigated whether short-term exposure to these fume particles results in changes in lung function and early stages of inflammatory reactions. METHODS: Twelve healthy, young male subjects were exposed to MAG fumes for 6 h with three different exposure concentrations in a three-fold cross-over study design. Exposure was performed in the "Aachen Workplace Simulation Laboratory" under controlled conditions with constant fume concentration. Fume concentrations were 0, 1, and 2.5 mg m(-3) in randomized order. Before and after each exposure, spirometry, and impulse oscillometry were performed and breath condensate samples were collected in order to quantify inflammatory markers like Nitrate, Nitrite, Nitrotyrosine, Hydroxyprolin and Malondialdehyde. RESULTS: A significant dependency on the exposure concentration could not be established for any of the endpoint parameters. CONCLUSION: In healthy, young subjects neither changes in spirometry nor changes in inflammatory markers measured in exhaled breath condensate could be detected after short-term exposure. PMID- 22311009 TI - Evaluation of working practices and surface contamination with antineoplastic drugs in outpatient oncology health care settings. AB - PURPOSE: Many antineoplastic drugs are classified as carcinogenic, mutagenic and teratogenic for humans. Therefore, minimization of exposure is required to reduce health risks to employees. The aim of this study was to evaluate working practices and safety measures during drug administration and to assess workplace contamination in outpatient oncology health care settings. METHODS: Questionnaires about working procedures were sent to 137 day hospitals and private practices. Workplace contamination with 5-fluorouracil, platinum, gemcitabine, cyclophosphamide, ifosfamide, methotrexate, docetaxel and paclitaxel was assessed using wipe samples. RESULTS: Forty institutions participated in the study, and in 28 departments, wipe samples were taken. Depending on the kind of activity, working procedures often (5-80%) were not confirmed with recommendations for safe handling of antineoplastic drugs. Altogether, 60.9% of the sampling results were above the limit of detection (LOD). Most frequent loads were detected with 5-FU (93.5%) and platinum (88.4%). Contamination was detected on all surfaces and the results ranged between =18 years). The pooled HR showed that Notch1 mutated group could not prolong EFS than Notch1 WT group both in children and adult patients. Although constitutively activated forms of the NOTCH1 receptor are potent inducers of T-ALL, our results suggest that Notch1 mutation could not become an indicator for EFS in T-ALL. PMID- 22311011 TI - Two types of ATPases from the Pacific white shrimp, Litopenaeus vannamei in response to environmental stress. AB - V-H ATPase and NaK ATPase are important classes of ATP-driven proton pumps that are present in the intracellular and plasma membranes of eukaryotic cells and play diverse roles in both normal and abnormal cellular processes. Among the subunits of the V-H ATPase complex, subunit a is a transmembrane glycoprotein that plays crucial roles in metabolism, growth, survival and cellular immunity. NaK ATPase subunit beta is thought to participate in the proper folding and movement of the NaK ATPase enzyme and may also aid cation transport. In this study, we analyzed the functions of V-H ATPase subunit a and NaK ATPase subunit beta from the Pacific white shrimp, Litopenaeus vannamei. Full-length cDNAs of the genes corresponding to V-H ATPase subunit a and NaK ATPase subunit beta were obtained, which were 2654 and 2055 bp long, with open reading frames encoding 830 and 313 amino acids, respectively. RT-PCR analysis indicated that mRNA transcripts were strongly (but differentially) expressed in the gills and hepatopancreas, and at lower levels in other shrimp tissues. In this study, for the first time, the gene expression of V-H ATPase subunit a and NaK ATPase beta of white shrimp Litopenaeus vannamei were analysed by quantitative real-time PCR after exposure to five kinds of environmental stresses (bacteria, pH, Cd, salinity and low temperature). The results demonstrate that both of the two genes are sensitive and involved in all different stress responses and are more sensitive to salinity than other stresses. And they may have relationship with the anti-stress mechanism induced by environment stress in shrimp. PMID- 22311012 TI - Molecular cloning of the Robl gene from Bombyx mori and studies of its developmental and physicochemical regulation. AB - Dynein light chains function as motor acceptor to recruit cargos, which play vital roles in many cellular processes such as intracellular transport and mitosis. In this study, we cloned and expressed the dynein light chain LC7 gene BmRobl in silkworm. The full-length cDNA of the dynein light chain LC7 gene BmRobl is 757 bp and encoded 97 aa polypeptide. Its molecular weight was ~11 kDa confirmed by western blotting. The tissue and stage expression profile of BmRobl drafted by real time PCR revealed that presence of BmRobl transcript was examined in all tissue but prominent expression level was found in brain, wing disc, ovary and testis. In metamorphosis wing disc, BmRobl reached to peak during the prepupae stage compared with the larval and pupal stages. This indicated BmRobl might involve in wing discs development during metamorphosis. Besides, in vitro wing discs 20E cultivation was performed and BmRobl expression profile was detected. The results demonstrated that the BmRobl gene was significantly up regulated with increase of 20E concentration; the mRNA level peaked at 2 MUg/ml of 20E. However, the BmRobl expression nearly has no change cultivated by 20 MUg/ml 20E compared with 0.02 MUg/ml 20E. These indicated that BmRobl expression might directly or indirectly induced by 20E, besides, high concentration 20E was far too inducible, suggesting that low concentrations of ecdysteroid induce cell proliferation, whereas high concentrations inhibit cell proliferation. Moreover, the transport role of BmRobl was clarified by UV challenge and vanadate cultivation. Both the real time PCR and western blotting results showed that the BmRobl gene was degraded with increase in the concentration of sodium vanadate combined with elongation in the time of UV challenge. Interestingly, compared with the single treatment group and non-treatment group, the group treated by both sodium vanadate and UV have severe degradation. This indicated that UV and vanadate might down-regulate BmRobl synergetically. It was further speculated that BmRobl may function as a positive regulator of the dynein complex during cellular transport. PMID- 22311013 TI - The complete mitochondrial genome of the butterfly Apatura metis (Lepidoptera: Nymphalidae). AB - As an important pest in the Slender Leaved Willow (Salix alba), Apatura metis is called Freyer's purple emperor, and its mitochondrial genome is 15,236 bp long. The encoded genes for 22 tRNA genes, two ribosomal RNA (rrnL and rrnS) genes, and 13 protein-coding genes (PCGs), and a control region in the A. metis mitochondria are highly homologous to other lepidopteran species. The mitochondrial genome of A. metis is biased toward a high A + T content (A + T = 80.5%). All protein coding genes, except for COI begins with the CGA codon as observed in other lepidopterans, start with a typical ATN initiation codon. All tRNAs show the classic clover-leaf structure, except that the dihydrouridine (DHU) arm of tRNA(Ser(AGN)) forms a simple loop. The A. metis A + T-rich region contains some conserved structures including a structure combining the motif 'ATAGA' and 19 bp poly (T) stretch, which is similar to those found in other lepidopteran mitogenomes. The phylogenetic analyses of lepidopterans based on mitogenomes sequences demonstrate that each of the six superfamilies is monophyletic, and the relationship among them is (((Noctuoidea + (Geometroidea + Bombycoidea)) + Pyraloidea) + Papilionoidea) + Tortricoidea. In Papilionoidea group, our conclusion argues that ((Lycaenidae + Pieridae) + Nymphalidae) + Papilionidae. PMID- 22311014 TI - Cytomegalovirus infection and coronary heart disease risk: a meta-analysis. AB - The chronic inflammatory process including cytomegalovirus (CMV) infection has been hypothesized to induce the progression of atherosclerosis in coronary heart disease (CHD). Numbers studies were conducted to analyze the association between CMV infection and risk of CHD, but no clear consensus had been reached. To assess this relationship more precisely, a meta-analysis was performed. The electronic databases PubMed, Embase, and CNKI were searched; data were extracted and analyzed independently by two investigators. Ultimately, 55 studies, involving 9,000 cases and 8,608 controls from six prospective studies (all with a nested case-control design) and 49 retrospective case-control studies were included. Overall, people exposed to CMV infection had an odds ratio (OR) of 1.67 (95% CI, 1.56-1.79) for CHD risk, relative to those not exposed. CMV infection was clearly identified as a risk factor for CHD in both prospective studies (OR, 1.31; 95% CI, 1.132-1.517) and retrospective studies (OR, 1.79; 95% CI, 1.659-1.939), and in both Asian group (OR, 2.69; 95% CI, 2.304-3.144) and non-Asian group (OR, 1.48; 95% CI, 1.371-1.600). Interestingly, in the subgroup analyses by detection methods of CMV, the increased risk (OR, 8.121) was greater among studies using polymerase chain reaction than the risk (OR, 1.561) among studies using enzyme linked immunosorbent assay. In conclusion, this meta-analysis suggested that CMV infection is associated with an increased risk for CHD, especially among Asian populations. PMID- 22311015 TI - Common variant (rs9939609) in the FTO gene is associated with metabolic syndrome. AB - Recent genome-wide association studies have showed that common variant (rs9939609) in fat mass and obesity associated (FTO) gene was significantly associated with type 2 diabetes through an effect on human body mass index/obesity. Further studies have suggested that this variant was also involved in the development of metabolic syndrome (MetS). However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association between rs9939609 polymorphism and the risk of MetS. Published literature from PubMed, EMBASE and other databases were searched. All studies assessing the association between rs9939609 polymorphism and the risk of MetS were identified. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed-effects model. Thirteen studies (8,370 cases and 23,156 controls) using NCEP ATPIII criteria for MetS were pooled with a meta-analysis. The overall result showed that there was a statistically significant association between rs9939609 polymorphism and MetS risk (OR = 1.11, 95% CI = 1.06-1.17). Subgroup analysis based on ethnicity showed that effect size was only statistically significant in Europeans (OR = 1.11, 95% CI = 1.05-1.16). Eight studies (1,256 cases and 2,551 controls) using IDF criteria for MetS were pooled with a meta-analysis. The overall analysis suggested that rs9939609 polymorphism was significantly associated with MetS risk (OR = 1.32, 95% CI = 1.13-1.54). Subgroup analysis stratified by ethnicity suggested that effect size was only statistically significant in Asians (OR = 1.33, 95% CI = 1.10-1.61). Our results suggested that FTO rs9939609 polymorphism was significantly associated with the increased risk of MetS in European and Asian populations. Mechanistic investigation is also needed to clarify the effect of FTO gene in the predisposition to MetS. PMID- 22311016 TI - Investigation of four porcine candidate genes (H-FABP, MYOD1, UCP3 and MASTR) for meat quality traits in Large White pigs. AB - Meat quality traits are economically important traits of swine, and are controlled by multiple genes as complex quantitative traits. In the present study four genes, H-FABP (heart fatty acid-binding protein), MASTR (MEF2 activating motif and SAP domain containing transcriptional regulator), UCP3 (uncoupling protein 3) and MYOD1 (myogenic differentiation 1) were researched in Large White pigs. The polymorphisms H-FABP T/C of 5'UTR, MYOD1 g.257 A>C, UCP3 g.1406 G>A in exon 3 and MASTR c.187 C>T have been reported to be associated with meat quality traits in pigs. The aim of this study was to analyze the effect of single and multiple markers for single traits in Large White pigs. The single marker association analysis showed that the H-FABP and MASTR genes were associated with IMF (intramuscular fat content) (P < 0.05), and that the g.257 A>C of MYOD1 gene was most significantly related to muscle pH value (P < 0.01). The multiple markers for IMF were analyzed by combining the markers and quantitative trait modes into the linear regression. The results revealed that H-FABP and MASTR integrate gene networks for IMF. Thus, our study results suggested that H-FABP and MASTR polymorphisms could be used as genetic markers in the marker-assisted selection towards the improvement of IMF in Large White pigs. PMID- 22311017 TI - Pregnenolone sulfate decreases intraocular pressure and changes expression of sigma receptor in a model of chronic ocular hypertension. AB - Sigma receptors are Ca(2+)-sensitive, ligand-operated receptor chaperones at the mitochondrion-associated endoplasmic reticulum membrane. This study describes the effect of the sigma receptor 1 agonist pregnenolone sulfate on intraocular pressure (IOP) and sigma receptor 1 expression in rat retinas after chronic ocular hypertension. Chronic ocular hypertension was induced by occlusion of episcleral veins. Retinal histological sections were obtained to determine inner plexiform layer thickness and the number of cell bodies in the ganglion cell layer. Sigma receptor expression in rat retinas was analyzed by RT-PCR and Western blotting. Cauterization caused IOP to increase >73%, and the pressure was maintained for 2 months. A time-dependent loss of ganglion cells and retinal thickness occurred at elevated IOP. High IOP decreased sigma receptor 1 expression during the first week, but expression was increased at 8 weeks. Injected pregnenolone significantly decreased IOP, prevented ganglion cell loss, protected inner plexiform layer thickness, and increased sigma receptor 1 expression in episcleral vein-cauterized rats. Sigma receptors appear to be neuroprotective and potential targets for glaucoma therapeutics. PMID- 22311018 TI - Loss of E-cadherin promotes the growth, invasion and drug resistance of colorectal cancer cells and is associated with liver metastasis. AB - The recent studies indicated that the epithelial cell adhesion molecule E cadherin is a well-recognized molecule that is important in cell adhesion. To further investigate the molecular basis of this notion, we used small-interfering RNA to inhibit E-cadherin function and found that loss of E-cadherin promoted Colorectal cancer cell growth, invasion and drug resistance through induction of beta-catenin nuclear translocation and epithelial-to-mesenchymal transition. Further analysis of E-cadherin expression with clinicopathologic parameters showed that E-cadherin expression decreased in Colorectal cancer patients who developed liver metastasis (P = 0.043). These findings indicate that E-cadherin loss in tumors contributes to progression and metastatic dissemination. Thus, E cadherin can act as a central modulator of the cell biological phenotypes and a potential prognostic marker in Colorectal cancer. PMID- 22311019 TI - Association of polymorphism of the beta(1, 4)-galactosyltransferase-I gene with milk production traits in Holsteins. AB - The beta(1,4)-galactosyltransferase-I gene (beta4galt1) encodes the catalytic part of the enzyme lactose synthase, responsible of lactose synthesis in the mammary gland. The complete coding region of the gene was screened for the presence of allelic variation among a sample of 1,200 Iranian Holstein cows, using PCR-SSCP technique followed by sequencing. Nine polymorphic nucleotide sites were identified-one in exons I and VI, two in exons II and III, and three in exon V. Altogether 18 different genotypes were assigned. Statistical analysis showed that the genotypes of Beta4GALT1 significantly affect milk, lactose, protein and total solid productions in both the first and second lactation (P < 0.001). Variance component analysis considering restricted maximum likelihood showed that the major factor making differences in milk, lactose, protein and total solid productions among the studied cow is the beta4galt1 genotype. We concluded that the beta4galt1 gene is potentially associated with milk production traits in dairy cows and should be considered for further studies on genetics of the milk production traits. PMID- 22311020 TI - Evaluation of ERalpha and VDR gene polymorphisms in relation to bone mineral density in Turkish postmenopausal women. AB - It has been suggested that the estrogen receptor alpha (ERalpha) and vitamin D receptor (VDR) genes as possibly implicated in reduced bone mineral density (BMD) in osteoporosis. The present study investigated the relation of ERalpha PvuII/XbaI polymorphisms and VDR FokI/TaqI polymorphisms with BMD in Turkish postmenopausal women. Eighty-one osteoporotic and 122 osteopenic postmenopausal women were recruited. For detection of the polymorphisms, polymerase chain reaction-restriction fragment lenght polymorphism techniques have been used. BMD was measured at the lumbar spine and hip by dual-energy X-ray absorptiometry. Distributions of ERalpha (PvuII dbSNP: rs2234693, XbaI dbSNP: rs9340799) and VDR genotypes (FokI dbSNP rs10735810, TaqI dbSNP: rs731236) were similar in study population. Although overall prevalence of osteoporosis had no association with these genotypes, the prevalence of decreased femoral neck BMD values were higher in the subjects with ERalpha PvuII "PP" and ERalpha XbaI "XX" genotypes than in those with "Pp/pp" genotypes and "xx" genotype, respectively (P < 0.05). Furthermore, subjects with VDR FokI "FF" genotype had lower BMD values of femoral neck and total hip compared to those with "Ff" genotype (P < 0.05). In the logistic regression analysis, we confirmed the presence of relationships between the VDR FokI "FF" genotypes, BMI <= 27.5, age >= 55 and the increased risk of femoral neck BMD below 0.8 value in postmenopausal women. The present data suggests that the ERalpha PvuII/XbaI and VDR FokI polymorphisms may contribute to the determination of bone mineral density in Turkish postmenopausal women. PMID- 22311021 TI - Soluble form of the endothelial adhesion molecule CD146 binds preferentially CD16+ monocytes. AB - The cell adhesion molecule CD146 is normally located at the endothelial cell-to cell junction and colocalizes with actin cytoskeleton. The soluble form of CD146 (sCD146) has been identified in the endothelial cell supernatant and in normal human plasma, and is increased in pathologic conditions with altered endothelial function. Soluble CD146 binding to monocytes promotes their transendothelial migration, which represents a central step in the development of atherosclerotic plaque. Since peripheral blood monocytes are characterized by a phenotypic and functional heterogeneity, with different transendothelial migration capacity, we hypothesized that monocyte subsets differently bind sCD146. Based on surface CD14 and CD16 expression monocytes were distinguished by flow cytometry (FACS) into three subsets: CD14++/CD16-, CD14++/CD16+ and CD14+/CD16+. CD16+ monocytes have been found to possess higher transendothelial migration ability. FACS analysis on blood monocytes from 30 healthy subjects revealed that higher percentages of CD14++/CD16+ (median, first and third quartile: 2.26, 1.62-3.87) and of CD14+/CD16+ (2.59, 1.28-4.80) were positive for CD146 (both p < 0.01), in comparison to CD14++/CD16- (0.66, 0.47-1.01). Moreover, in vitro treatment of ficoll separated monocytes with recombinant CD146 showed that both CD16+ subsets increased their percentage of CD146-positive events compared to CD16- monocytes (p < 0.01). Soluble CD146 levels were evaluated by ELISA in plasma samples of subjects from our study group and showed a correlation with percentage of CD146 positive CD14+/CD16+ monocyte subset. In this work we have demonstrated that monocyte subsets behave differently with regard to their sCD146 binding activity; because binding of CD146 influences transendothelial migration of monocytes, modulation of monocyte-CD146 interaction may represent a potential target to limit atherosclerotic plaque development. PMID- 22311022 TI - Genetic variations in SREBP-1 and LXRalpha are not directly associated to PCOS but contribute to the physiological specifics of the syndrome. AB - The polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder consisting of reproductive disturbances associated with all aspects of the metabolic syndrome and genetic components in the pathology of this complex disease is very likely. Accordingly, variations in single genes might affect specific features of PCOS and thereby help to define different subgroups. SREBP-1 or LXRalpha have been shown to be genetically linked to lipid metabolism or insulin sensitivity. As these are two major aspects of the PCOS phenotype, we evaluated both genes in a cohort of 153 PCOS patients. Analyses of both genes revealed in SREBF-1, i.e. SREBP-1a and SREBP-1c, not any variation and in the LXRalpha gene no novel sequence variations. Common variants of LXRalpha (rs2279238:G; all:0.8658; PCOS:0.8627; controls: 0.8686 or A: all:0.13412; PCOS:0.1373; controls:0.1314; (OR (95% CI) 0.9508 (0.4226-2.1385); rs11039155: G: all:0.8767; PCOS:0.8663; controls:0.8857 and A all:0.1233; PCOS:0.1337; controls:0.1143; (OR (95% CI) 0.8383 (0.3618-1.9371)) were also not directly associated to PCOS. Combined analyses of both polymorphism revealed that there was no difference of distribution between the groups. In contrast, analyses of the impact of these polymorphisms on metabolic parameters of the syndrome indicated significant differences related to genotypes. The data indicated that rs11039155 increases metabolic risk, whereas rs2279238 has a protective effect on the overall metabolic risk. The investigation of the PCOS group presented indicates that the combined analyses of variations in putative candidate genes allowed a genotype-phenotype correlation for metabolic features. PMID- 22311023 TI - Tolbutamide hydroxylation by hepatic microsomes from Atlantic salmon (Salmo salar L.). AB - Metabolic transformations of two substrates for human cytochrome P450 (CYP450) 2C9, tolbutamide and diclofenac, were investigated in hepatic microsomes from Atlantic salmon (Salmo salar L.). Tolbutamide hydroxylation followed Michaelis Menten kinetics. Mean apparent Michaelis-Menten constant (K(m)) and maximum reaction velocity (V(max)) values for 4-hydroxytolbutamide (TBOH) formation were 0.09 +/- 0.031 mM and 49.5 +/- 6.03 pmol/min/mg, respectively. Addition of sulfaphenazole, an inhibitor for mammalian CYP2C9, in a range from 1 to 200 MUM decreased formation of TBOH in a concentration-dependent manner, but not to 50%. Neither fluconazole, an inhibitor of human CYP2C9, nor ketoconazole, inhibitor of CYP1A and CYP3A in fish, affected TBOH formation. In contrast ellipticine, an inhibitor of CYP1A in fish inhibited TBOH formation with the IC(50) value of 12.1 MUM. The rate of TBOH formation was competitively inhibited by 100 MUM of sesamin in the incubations, but the degree of inhibition did not increase with increased sesamin concentration. Ethoxyresorufin hydroxylase (EROD) activity was inhibited by tolbutamide in a non-competitive manner (inhibition constant K(i) = 218 MUM). Our data suggest that tolbutamide is metabolized by salmon microsomes with formation of TBOH. CYP1A might be involved in this reaction as suggested by decreased TBOH formation in the presence of ellipticine and decreased EROD activity in the presence of tolbutamide. Incubation of diclofenac with the microsomes yielded no metabolite formation, suggesting that salmon does not possess diclofenac-metabolizing activity. PMID- 22311024 TI - Association of thrombospondin 1 gene with schizophrenia in Korean population. AB - Thrombospondin 1 (THBS1), a multi-domain glycoprotein, is secreted from astrocytes and promotes synaptogenesis. Increasing evidence has suggested that not only various markers for synaptic pathology, but also astrocytes are affected in schizophrenia. In this study, we investigated whether coding region single nucleotide polymorphisms (cSNPs) of the THBS1 gene were associated with schizophrenia and with the clinical symptoms of schizophrenia patients. We genotyped two cSNPs [rs2228261 (Asn470Asn) and rs2292305 (Thr523Ala)] using direct sequencing in 220 schizophrenia patients and 376 control subjects. In this study, rs2228261 revealed significant association with schizophrenia in both codominant (TT vs. CC, P = 0.009, OR = 2.10, 95% CI = 1.23-3.59) and recessive models (TT vs. CC/CT, P = 0.0012, OR = 2.28, 95% CI = 1.38-3.77). Also, rs2292305 was associated with schizophrenia in the recessive model (GG vs. AA/AG, P = 0.0052, OR = 2.05, 95% CI = 1.24-3.38). Additionally, in the analysis of the haplotype, the CA and TG haplotypes consisting of rs2228261 and rs2292305 were associated with schizophrenia in the dominant (P = 0.019, OR = 1.79, 95% CI = 1.10-2.90) and recessive models, respectively (P = 0.0086, OR = 0.51, 95% CI = 0.31-0.84). In further analysis according to the clinical symptoms, rs2292305 showed a weak association with the poor concentration symptoms of schizophrenia patients in the dominant model (AG/GG vs. AA, P = 0.024, OR = 2.04, 95% CI = 1.09 3.83). The results suggest that the THBS1 gene may contribute to the susceptibility of schizophrenia. PMID- 22311025 TI - Isolation and characterisation of an HpSHP gene from Hosta plantaginea. AB - Based on genetic and molecular analyses, the ABC model has been proposed to explain the genetic control of floral development. C-class MADS-box genes play crucial roles in Arabidopsis thaliana development by regulating the organ identities of stamens and gynoecium. The present research reports for the first time the cloning of an HpSHP gene from Hosta plantaginea (Lam.) Aschers. Phylogenetic analysis shows that HpSHP is a member of the C-class MADS-box genes that is closely related to C-lineage SHP homologues from monocot species. Semi quantitative and real-time polymerase chain reaction analyses show that HpSHP expression is stamen and gynoecium specific. HpSHP also has spatial and temporal expression patterns in the reproductive organs of H. plantaginea. A functional analysis is carried out in Arabidopsis by overexpression of HpSHP. Homeotic transformations of sepals into carpelloid organs, bent ovaries, and prematurely shattering fruits are observed in 35S::HpSHP transgenic plants. All these results show that HpSHP plays a crucial role in gynoecium development. PMID- 22311026 TI - IL-1beta (-511T/C) gene polymorphism not IL-1beta (+3953T/C) and LT-alpha (+252A/G) gene variants confers susceptibility to visceral leishmaniasis. AB - Lymphotoxin-alpha (LT-alpha) and interleukin-1beta (IL-1beta) are proinflammatory cytokines playing important roles in immunity against Leishmania infection and the outcome of the disease. As cytokine productions are under the genetic control, this study tried to find any probable relationship between these cytokine gene polymorphisms and the susceptibility to visceral leishmaniasis in Iranian pediatric patients. Ninety-five pediatric patients involved with visceral leishmaniasis and 128 non-relative healthy people, from the same area as the patients, were genotyped for LT-alpha (+252A/G) and IL-1beta (+3953T/C and 511T/C) gene polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). There was not found any significant differences in allele and genotype frequencies of LT-alpha (+252A/G) and IL-1beta (+3953) among the study groups. However, the frequency of IL-1beta -511TT genotype was higher in the controls (P = 0.0004) while the frequency of IL-1beta -511CC genotype and C allele were higher in the patients (P = 0.008 and P = 0.00006, respectively). Furthermore, IL-1beta CC (-511/+3953) haplotype was more frequent in VL patients compared with the controls (P = 0.0002) and the distribution of TT haplotype was higher in the controls compared with the patients (P = 0.003). In conclusion, based on the results, IL-1beta -511C allele, CC genotype and CC ( 511/+3953) haplotype could be considered as the susceptibility factors for visceral leishmaniasis while IL-1beta -511TT genotype, T allele and TT haplotype (-511/+3953) might be counted as the influential factors for resistance to the disease. PMID- 22311027 TI - Pyrosequencing of a short fragment of the amelogenin gene for gender identification. AB - We report a pyrosequencing method for detecting a short amelogenin fragment to aid the gender identification. The PCR products (44/45 bp), including primers and target sequence (4/5 bp) consisting of three point mutations and one indel mutation, were sequenced by the pyrosequencing method. 100 randomly chosen DNA samples of healthy donors were analyzed with this method, and all of them were correctly typed. The sensitivity of the technique was 0.5 ng template DNA. No specific peak was found in any detected animals or organisms except for monkey. For blood samples that were left outside for 26 weeks and DNA degraded artificially by digesting with DNaseI, this method gave more accurate results than the conventional method. Moreover, four bone samples analyzed using the method gave clear pyrograph. This method is easy, quick, cheap and suitable for high-throughput analysis, especially for identifying the gender of highly degraded DNA samples. PMID- 22311028 TI - Molecular characterization of the porcine STAT4 and STAT6 genes. AB - Signal transducers and activators of transcription (STATs) are members of a recently identified family of transcription factors that activate gene transcription in response to a number of different cytokines. STAT4 and STAT6 were activated by interleukin (IL)-12 and IL-4 stimulation, which were important for the generation of Th1 and Th2 cells. In this study, we cloned the cDNA sequences and analyzed the genomic structure of porcine STAT4 (poSTAT4) and STAT6 (poSTAT6) genes. Chromosome localization assigned these two genes to SSC15 and SSC5, and they were most closely linked to maker SWR1002 and DK. The RT-PCR revealed that both genes were expressed in eight diverse tissues, with the highest level in small intestine, followed by lung, kidney, muscle and stomach, whereas expressions in heart, liver and spleen were relatively weak. Transient transfection indicated that poSTAT4 and poSTAT6 proteins distributed throughout the whole porcine hip artery endothelial cell. A single nucleotide polymorphism (A/G), which can be recognized by restriction enzyme TaiI, was identified at the 3' untranslated region of poSTAT6, and genotyping results showed apparent variation in allele frequency between Chinese indigenous and western breeds. PMID- 22311029 TI - Analysis of polymorphism within POU1F1 gene in relation to milk production traits in dairy Sarda sheep breed. AB - The ovine POU1F1 gene is localized on chromosome 1 and it contains five introns and six exons. In different mammalian species some mutations in different exons are associated with different production traits. The aim of our research was to study the POU1F1 gene nucleotide sequence to detect possible polymorphisms and their relationships with milk productive traits in Sarda breed sheep. The study had been conducted on 140 ewes, 4 or 5 years old coming from a farm located in Sardinia. All the animals were multiparous, lactating and in their third to fifth lactation. Individual milk yield had been recorded monthly and for each sample fat, protein, casein, lactose, and somatic cell count values were analysed. A jugular blood sample was collected from each ewe to perform genomic DNA extraction. PCR, SSCP and sequencing analysis were carried out to examine the six exons to highlight possible SNPs. One-way ANOVA was used to analyse association of variants with milk yield and/or its composition. Two novel SNP were found: 121 C>T in the 5'UTR of the fourth intron fragment and 249 G>A in the 3'UTR of the sixth exon fragment. The statistical analysis did not shown association between milk productive traits and the found polymorphisms. However, further investigations about the promoter region or the prophet genes, like the PROP-1, could clarify its exact role in regulating the productive traits in sheep. PMID- 22311030 TI - Association of the microRNA-499 variants with susceptibility to hepatocellular carcinoma in a Chinese population. AB - microRNAs (miRNAs) are a new class of small non-coding RNAs that function as tumor suppressors or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNA may contribute to cancer development. We hypothesized that genetic variations of the miRNA could be associated with the risk of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A total of 100 patients with HCC, 100 cases of chronic hepatitis B and 100 health adults were enrolled in this present study. Two common polymorphisms in pre-miRNAs: Homo sapiens miRNA-146a (hsa-mir-146a) (rs291016, guanine to cytosine [G-C]) and hsa-mir-499 (rs3746444; adenine to guanine [C-T]) were genotyped by PCR-Restriction Fragment Length Polymorphism and confirmed by bidirectional DNA sequencing. Significant differences were found in frequency and distribution of the genotypes of miRNA-499 between the HCC and the control group. Compared with miRNA-499 T/T, the odds ratio (OR) of patients with miRNA-499 C/C for developing HCC was 3.630 (95% CI: 1.545-8.532), and OR for developing HBV-related HCC was 3.133 (95% CI: 1.248-7.861). There was no significant association between miRNA-146a polymorphism and the risk of HCC in all subjects. Our results suggested that hsa-mir-499 polymorphism was associated with susceptibility to HBV-related HCC in Chinese population. Further characterization of miRNA SNPs may open new avenue for the study of cancer and therapeutic interventions. PMID- 22311031 TI - Characterization and expression analysis of prohibitin in the testis of Chinese mitten crab Eriocheir sinensis. AB - Prohibitin plays a key role in maintaining mitochondrial membrane integrity and retaining its normal function. We have initially cloned and sequenced the cDNA of prohibitin from testis of the crab Eriocheir sinensis. The 1,357 bp Prohibitin cDNA comprises a 105 bp 5' untranslated region, a 427 bp 3' untranslated region and a 825 bp open reading frame. Protein alignment substantiates that the Prohibitin has 70.2, 69.8, 70.5, 70.9, 72.4, 70.6 and 74.9% identity with its homologues in Mus musculus, Homo sapiens, Gallus gallus, Danio rerio, Xenopus tropicalis, Drosophila mojavensis and Aedes aegypti, respectively. In situ hybridization revealed that the Prohibitin mRNA was mainly localized around the proacrosomal vesicle and nucleus membrane in early-stage spermatid. In the following middle stage, Prohibitin mRNA was situated inside the invaginated region of half-moon-like nucleus and surrounded the proacrosomal vesicle. In late stage spermatid, the mRNA was aggregated in the acrosomal tubule, the band between the acrosome and cup-like nucleus, remanent cytoplasm as well. In the mature sperm, mRNA was only found in the acrosomal tubule and the limited space between the nucleus and acrosome. Therefore, we presume that Prohibitin may fulfill critical functions in the spermiogenesis of Eriocheir sinensis. PMID- 22311032 TI - Haplotype analysis of the polymorphic 17 YSTR markers in Kerala nontribal populations. AB - The origin of the Kerala non tribal population has been a matter of contention for centuries. While some claim that Negritos were the first inhabitants, some historians suggest a Dravidian origin for all Keralites. The aim of our study has been to provide sufficient scientific evidence based on Y chromosome short tandem repeat (Y STR) analysis for tracing the paternal lineage and also to create a database of the Y STR haplotype of the male population for future forensic analysis. Whole blood samples (n = 168) were collected from unrelated healthy men of the Kerala non-tribal population over a period of 2 years from October 2009. Genomic DNA was extracted by salting out method. All samples were genotyped for the 17 Y STR loci by the AmpFLSTR Y-filer PCR Amplification Kit. The haplotype and allele frequencies were determined by direct counting and analyzed using Arlequin 3.1 software, and molecular variance was calculated with the Y chromosome haplotype reference database online analysis tool, www.yhrd.org . Haplotype diversity was calculated using HaPYDive ( http://portugene.com/hapydive.html ). The majority of haplotypes were unique (149/168). The variant allele 17.1 was observed in DYS 385 loci in three samples. Fifteen samples (8.93%) showed the presence of alleles that are not within the established marker range denoted as outside marker range (OMR). The allele frequency of Kerala non tribal population ranged from 0.00003 to 0.5809. The most polymorphic single locus marker was DYS 458. The haplotype diversity value for Kerala non tribal population was 0.9978. The pairwise difference value ranged from 0.0531 to 0.0854 on comparison of the haplotypes of the Kerala non tribals with other Indian populations. The multi dimensional scaling plot depicted the proximity of Kerala non tribal population with Vasterbotten population (Swedish) and Paiwan, Patyal population of Taiwan, Thailand, and Zhuang population of China. The results of the study indicate towards a European paternal lineage in the non tribal Kerala population. PMID- 22311033 TI - The 4a/4a genotype of the VNTR polymorphism for endothelial nitric oxide synthase (eNOS) gene predicts risk for proliferative diabetic retinopathy in Slovenian patients (Caucasians) with type 2 diabetes mellitus. AB - Thus far only a limited number of studies examined the association between endothelial nitric oxide synthase (eNOS) polymorphisms and proliferative diabetic retinopathy (PDR). In this report, two polymorphisms in the eNOS gene have been investigated, namely the 894G>T (Glu298Asp) and a 27 bp VNTR (4b/4a), to assess their possible relationships to PDR among Slovenian (Caucasians) type 2 diabetic patients. This cross-sectional case-control study enrolled 577 unrelated Slovenian subjects (Caucasians) with type 2 diabetes mellitus. The case group consisted of 172 patients with PDR and the control group had 405 patients who had no clinical signs of diabetic retinopathy (DR) but did have type 2 diabetes for more than 10 years' duration. Genotyping of eNOS polymorphisms was carried out with conventional and real-time PCR assays. A significantly higher frequency of the eNOS minor "4a" allele was found in patients with PDR than in controls (23.6 versus 17.7%, p = 0.01). Moreover, the univariate analysis showed a significant association of the 27 bp VNTR 4a/4a genotype and PDR in the recessive model. The odds ratio (OR) of PDR for the 4a/4a genotype to 4b/4a plus 4b/4b was 2.9 (95% CI 1.3-6.2, p = 0.005). Further, the presence of 4a/a genotype was associated with a 3.4-fold (95% CI 1.4-8.6, p = 0.009) increased risk for PDR while adjusted for other risk factors. This is the first study to implicate eNOS 4a/4a homozygous deletion, and hence the "4a" allele, as the genetic risk factors for PDR in Caucasians. PMID- 22311034 TI - Haplotype combinations of AdPLA gene polymorphisms associate with growth traits in Chinese cattle. AB - Ablation of AdPLA in mice could prevent obesity, which implicated AdPLA was a new candidate gene for growth traits. In this study, we screened the polymorphisms of AdPLA gene and revealed three novel SNPs (NC_007330.4:g.43638506 C>T, 43658457 T>C and 43661404 T>C) by DNA sequencing and forced PCR-RFLP methods in 1340 individuals from six breeds. A preliminary single SNP-traits association analysis demonstrated that CC genotype was significantly higher than TT genotype at two growth traits in P6-EcoRII locus (P < 0.05). Moreover, the P8-FbaI locus had a significant association with some growth traits, individuals with TT genotype were higher than CC genotype (P < 0.05). A further analysis confirmed that these two SNPs were in linkage disequilibrium, and haplotype H2, both advantage allelic in P6-EcoRII and P8-FbaI loci, was better than the others for bovine growth traits, which was consistent with single SNP-traits association results. Therefore, this study not only proved that these SNPs were in association with bovine growth traits, but also contributed to evaluate them as genetic markers in bovine genetics and breeding and had potential application in breeding programs. PMID- 22311035 TI - Association between MTHFR C677T polymorphism and osteonecrosis of the femoral head: a meta-analysis. AB - The results of studies on association between the C677T polymorphism of the 5,10 methylene-tetrahydrofolate reductase (MTHFR) gene and osteonecrosis of the femoral head (ONFH) are controversial. To derive a more precise estimation of the relationship between the MTHFR C677T polymorphism and ONFH, a meta-analysis was performed. Eight studies on MTHFR C677T association with ONFH were searched up to April 2011, and the genotype frequencies in control group were consistent with Hardy-Weinberg equilibrium. The effect summary odds ratio (OR) and 95% confidence intervals were obtained. Publication bias was tested by funnel plot, Egger's regression test, and heterogeneity was assessed. Eight studies containing 778 cases and 1,162 controls were included. Heterogeneity was observed (chi(2) = 18.58, P = 0.01). Under the random effects model, the common OR was 1.38 (95% CI: 0.92-2.08; P = 0.12). In the subgroup meta-analysis, there was an association between MTHFR C677T polymorphism and ONFH in non-Asian population for CT + TT vs. CC (OR = 1.72; 95% CI: 1.21-2.43; P = 0.002; I(2) = 37.9%, P = 0.17), but not for Asian population (OR = 0.88; 95% CI: 0.66-1.66; P = 0.35; I(2) = 45.4%, P = 0.16). There was heterogeneity between studies and no clear evidence of an association on a worldwide population. When stratifying for the race, this meta analysis did not provide an evidence of confirming association between MTHFR C677T polymorphism and ONFH. The large sample and well-designed study based on different ethnic groups should be considered in future associated studies to clarify the association of MTHFR C677T polymorphism with ONFH susceptibility. PMID- 22311036 TI - Effect of gestational protein deficiency and excess on hepatic expression of genes related to cell cycle and proliferation in offspring from late gestation to finishing phase in pig. AB - Maternal diet during gestation is known to affect offspring phenotype induction. In the present study the influence of maternal protein restriction and excess during gestation on offspring candidate gene expression was analysed. German Landrace gilts were fed control, low protein (LP) or high protein (HP) diet throughout gestation (n = 18 per diet group). After birth piglets were cross fostered and lactated by control diet fed nursing sows. Samples of offspring liver tissue were taken at foetal, newborn, weaning and finishing phase (n = 16, respectively). Transcript amount of selected candidate genes related to cell cycle and cell proliferation was estimated by quantitative real-time PCR. Maternal protein restriction influenced gene expression of candidate genes CCND2, GADD45B, GALK1, GSTP1, MARCKS, MGMT, NEAT1, PSEN1, SNX1 and TRPM7 in liver from foetuses, newborn piglets, weaned and/or finisher pigs. In the offspring of mothers fed a HP diet expression of target genes was affected exclusively in finisher pigs showing increased transcript amount of CCND2, GALK1, MARCKS, SNX1 and TRPM7. The results of the present study clearly show a long-lasting impact of the maternal protein supply during gestation on offspring candidate genes. Remarkably, effects of gestational HP diet became evident in finisher pigs while LP supply already alters genes expression in foetal tissue. Thus it is suggested that LP and HP supply affect the offspring in utero by different physiological mechanisms with the consequence of late effects in case of prenatal protein excess in contrast to early effects in case of protein restriction. PMID- 22311037 TI - Chlorophyllase in Piper betle L. has a role in chlorophyll homeostasis and senescence dependent chlorophyll breakdown. AB - Total chlorophyll content and chlorophyllase (chlorophyll-chlorophyllido hydrolase EC 3.1.1.14) activity in fresh leaves of Piper betle L. landrace KS was, respectively, twofold higher and eight fold lower than KV, showing negative correlation between chlorophyll and chlorophyllase activity. Specific chlorophyllase activity was nearly eightfold more in KV than KS. ORF of 918 nt was found in cloned putative chlorophyllase cDNAs from KV and KS. The gene was present as single copy in both the landraces. The encoded polypeptide of 306 amino acids differed only at two positions between the KV and KS; 203 (cysteine to tyrosine) and 301 (glutamine to glycine). Difference in chlorophyllase gene expression between KV and KS was evident in fresh and excised leaves. Up regulation of chlorophyllase gene by ABA and down regulation by BAP was observed in both the landraces; however, there was quantitative difference between KV and KS. Data suggests that chlorophyllase in P. betle is involved in chlorophyll homeostasis and chlorophyll loss during post harvest senescence. PMID- 22311038 TI - Association of IL-10-1082 promoter polymorphism with susceptibility to gastric cancer: evidence from 22 case-control studies. AB - Evidence suggested that interleukin-10 (IL-10) may be involved in the etiology of gastric cancer (GC). However, epidemiological studies on the association between IL-10-1082 promoter polymorphism and GC risk are still ambiguous. To quantitatively summarize the evidence for such a relationship, we performed a meta-analysis. Systemic searches of the PubMed and Medline databases were performed, with the last report up to July 2011. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. 22 independent studies including 4,289 cases and 5,965 controls were involved in this meta-analysis. Obvious association was found when all studies were pooled into the meta-analysis (A vs. G: OR = 0.489, 95% CI = 0.335-0.713, P < 0.001). In the subgroup analysis by ethnicity, we observed significant associations in Asians (A vs. G: OR = 0.651, 95% CI = 0.506-0.838, P = 0.001; AA vs. GG: OR = 0.482, 95% CI = 0.328-0.709, P < 0.001; AA/AG vs. GG: OR = 0.711, 95% CI = 0.527 0.959, P = 0.025; AA vs. AG/GG: OR = 0.701, 95% CI = 0.520-0.944, P = 0.019) and Caucasians (A vs. G: OR = 0.365, 95% CI = 0.140-0.949, P = 0.039), but not in Latino population. When stratified analysis by control sources, our results indicated that A allele decreased approximately 48% risk among population-based studies (A vs. G: OR = 0.524, 95% CI = 0.374-0.733, P < 0.001). Taken together, this meta-analysis suggests that IL-10-1082 polymorphism is associated with GC risk. PMID- 22311039 TI - Cloning and molecular characterization of a gene encoding late embryogenesis abundant protein from Pennisetum glaucum: protection against abiotic stresses. AB - Late embryogenesis abundant (LEA) protein family is a large protein family that protects other proteins from aggregation due to desiccation or osmotic stresses. A cDNA clone encoding a group 7 late embryogenesis abundant protein, termed PgLEA, was isolated from Pennisetum glaucum by screening a heat stress cDNA library. PgLEA cDNA encodes a 176 amino acid polypeptide with a predicted molecular mass of 19.21 kDa and an estimated isoelectric point of 7.77. PgLEA shares 70-74% sequence identity with other plant homologs. Phylogenetic analysis revealed that PgLEA is evolutionarily close to the LEA 7 group. Recombinant PgLEA protein expressed in Escherichia coli possessed in vitro chaperone activity and protected PgLEA-producing bacteria from damage caused by heat and salinity. Positive correlation existed between differentially up-regulated PgLEA transcript levels and the duration and intensity of different environmental stresses. In silico analysis of the promoter sequence of PgLEA revealed the presence of a distinct set of cis-elements and transcription factor binding sites. Transcript induction data, the presence of several putative stress-responsive transcription factor binding sites in the promoter region of PgLEA, the in vitro chaperone activity of this protein and its protective effect against heat and salt damage in E. coli suggest a role in conferring abiotic stress tolerance in plants. PMID- 22311040 TI - Construction of recombinant proteins for reprogramming of endangered Luxi cattle fibroblast cells. AB - Generation of induced pluripotent stem cells from endangered cattle breeds makes a significant contribution to the establishment of embryonic stem cell line, conservation and utilization of genetic resources in endangered cattle. In our study, we are trying to construct recombinant proteins of transcription factors Oct-4, Nanog, Sox2 and Lin28 for reprogramming of endangered Luxi cattle fibroblast cells in induced pluripotent stem cells. To test the cell permeability and stability of the recombinant proteins, we designed and fused a pep-1 protein transduction domain to the C-terminus of enhanced green fluorescent protein, we treated Luxi cattle fibroblast cells with the purified proteins at various concentrations by adding them to the cell culture media for 2-48 h and assayed cell morphology and protein presence. We found that the purified EGFP-tagged recombinant proteins readily entered cells at a concentration of 0.12 mg/ml within 2 h and some of them could translocate into nucleus. In addition, we found that the transduced proteins appeared to be stable inside cells for up to 48 h. Then codons of Oct-4, Nanog, Sox2 and Lin28 were optimized for high level of expression in E. coli., they were synthesized using DNA oligo based, PCR gene assembling method, the reprogramming factors were designed with optimized transcription factors fused a pep-1 protein transduction domain to the C terminus, for high level protein expression of the reprogramming factors, inducer concentration, and induction time were tested, the optimum inducer concentration for the expression of reprogramming factors Oct-4, Nanog, Sox2 and Lin28 were 0.01 mM, the optimum induction time were 10, 8, 2 and 12 h, respectively. PMID- 22311041 TI - Isolation, molecular characterization, and functional analysis of the vacuolar Na+/H+ antiporter genes from the halophyte Karelinia caspica. AB - The full-length cDNAs of two Karelinia caspica genes, KcNHX1 and KcNHX2, were isolated by RACE and RT-PCR based on the conserved regions of Na(+)/H(+) antiporter (NHX) genes from other halophyte species. The cloned KcNHX1 cDNA contained 2,022 nucleotides with an open reading frame (ORF) of 1,620 bp and the KcNHX2 cDNA contained 1,976 nucleotides with an ORF of 1,653 bp. The deduced amino acid sequences indicated that both genes were homologous to NHXs from other higher plants. To investigate the possible roles of KcNHX1 and KcNHX2 in the salt stress response of K. caspica and the underlying regulatory mechanisms, RNAi vectors were constructed and transformed into K. caspica to specifically silence endogenous KcNHX1 and KcNHX2. The physiological results showed that silencing KcNHX1 in K. caspica led to reduced salt tolerance in high concentrations of NaCl, suggesting that KcNHX1 plays an essential role in the response of K. caspica to salt stress. However, the inhibition of KcNHX2 seemed to have little influence on the salt resistance of transgenic plants, indicating that KcNHX2 may be relevant for functions other than salt tolerance in K. caspica. PMID- 22311042 TI - MDR1 C3435T polymorphism and cancer risk: a meta-analysis based on 39 case control studies. AB - Multidrug resistance 1 (MDR1) gene encodes the ATP-dependent cellular efflux pump P-glycoprotein (P-gp) which efflux of a variety of substances across the membrane. P-gp could serve a role in cancer etiology based on its physiological role of protecting cells from xenobiotics or metabolites. The C3435T (rs1045642) polymorphism of the MDR1 gene which could influence the P-gp expression and function have been implicated in the cancer risk. However, the results from the published studies on the association between this polymorphism and cancer risk are conflicting. To drive a more precise estimation of this association, we performed a meta-analysis of 39 case-control studies, including a total of 9,265 cancer cases and 13,502 controls. We used odds ratios (ORs) with their 95% confidence intervals (CIs) to assess the strength of the association. Overall, individuals with the MDR1 3435TT genotype were associated with an increased cancer risk than those with the CC (OR = 1.29, 95% CI: 1.10-1.51) or CT/CC (OR = 1.18, 95% CI: 1.04-1.34) genotypes, similar to the CT or CT/TT compared with the CC genotype. In the stratified analyses, the increased risks were more pounced among hematologic malignances (OR = 1.27, 95% CI: 1.10-1.46, P (heterogeneity) = 0.415), breast cancer (1.42, 1.04-1.94, 0.018), renal cancer (1.77, 1.28-2.46, 0.307), Caucasians (1.21, 1.07-1.38, 0.000) and population-based studies (1.20, 1.05-1.36, 0.000) in a dominant model. The results suggested that the MDR1 C3435T polymorphism may contribute to cancer risk. PMID- 22311043 TI - Association of Toll-like receptor (TLR) 2, 3 and 9 genes polymorphism with prostate cancer risk in North Indian population. AB - Prostate cancer (PCa) is the most common cancer among men. It has been suggested that toll like receptors (TLRs) may contribute to PCa pathogenesis by stimulating prostate epithelial cell proliferation in response to infectious stimuli. We performed case control study to analyze the genetic variants of TLR2, 3 and 9 gene polymorphisms with PCa risk in a North Indian population. For this study we genotyped age matched, unrelated 195 PCa patients and 250 healthy controls of similar ethnicity in a case-control study. They were genotyped for TLR2 (-196 to 174 Del), TLR3 (c.1377C/T) [rs3775290] and TLR9 (G2848A) [rs352140] gene polymorphisms using polymerase chain reaction and restriction fragment length polymorphism method. Variant allele Del (D) carriers i.e. (ID + DD) of TLR2 (-196 to -174 Del) SNP, demonstrated 1.57 fold increased risk (p = 0.040; OR = 1.57, 95% CI = 1.02-2.24) as compared to Ins (I) allele, suggesting a dominant effect model involved in the risk of this polymorphism in PCa. However, variants of TLR3 and 9 gene polymorphisms were not associated with PCa risk. Our results suggested the low penetrance variant of TLR2 (-196 to -174 Del) to be at increased PCa risk in North Indian population. Functional studies in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in identifying the disease-associated variants for PCa etiology. PMID- 22311044 TI - Genome-wide analysis of the ATP-binding cassette (ABC) transporter gene family in the silkworm, Bombyx mori. AB - The ATP-binding cassette (ABC) superfamily is a larger protein family with diverse physiological functions in all kingdoms of life. We identified 53 ABC transporters in the silkworm genome, and classified them into eight subfamilies (A-H). Comparative genome analysis revealed that the silkworm has an expanded ABCC subfamily with more members than Drosophila melanogaster, Caenorhabditis elegans, or Homo sapiens. Phylogenetic analysis showed that the ABCE and ABCF genes were highly conserved in the silkworm, indicating possible involvement in fundamental biological processes. Five multidrug resistance-related genes in the ABCB subfamily and two multidrug resistance-associated-related genes in the ABCC subfamily indicated involvement in biochemical defense. Genetic variation analysis revealed four ABC genes that might be evolving under positive selection. Moreover, the silkworm ABCC4 gene might be important for silkworm domestication. Microarray analysis showed that the silkworm ABC genes had distinct expression patterns in different tissues on day 3 of the fifth instar. These results might provide new insights for further functional studies on the ABC genes in the silkworm genome. PMID- 22311045 TI - Sequence characterization and expression pattern of BcMF21, a novel gene related to pollen development in Brassica campestris ssp. chinensis. AB - In this report a full length cDNA, Brassica campestris Male Fertile 21 (BcMF21) was successfully isolated from one of the cDNA-amplified fragment length polymorphism (cDNA-AFLP) transcript-derived fragments (TDFs), BBP10, that was found down-regulated in the flower buds of sterile plants in Brassica campestris L. ssp. chinensis Makino genic male sterile (GMS) AB line system (Bcajh 97 01A/B). BcMF21 protein structure analysis showed a signal peptide at the N terminus; two protein kinase C phosphorylation sites, five N-myristoylation sites and one casein kinase II phosphorylation site. The promoter region of BcMF21, a 779 bp upstream of ATG was isolated by thermal asymmetric interlaced-PCR (TAIL PCR). Bioinformatics analysis revealed that the promoter of BcMF21 contained several classical cis-acting elements and three pollen specific elements. Transient expression analysis showed that the promoter could drive green fluorescence protein (GFP) expression. Quantitative reverse transcript-PCR analysis revealed that BcMF21 was specifically expressed in flower buds. The transcript level of BcMF21 was much lower in the sterile flower buds than in the fertile flower buds in 'Bcajh 97-01A/B' system. In situ hybridization further showed that BcMF21 was only expressed in the tetrads and the microspores at the tetrad stage and the uninucleate stage. In addition, phylogenetic analysis demonstrated that the BcMF21 was relative conserved within family Crucifereae and might be originated from the ancestor diploid B. campestris within genus Brassica according to the Triangle of U theory. PMID- 22311046 TI - Novel and recurrent LDLR gene mutations in Pakistani hypercholesterolemia patients. AB - The majority of patients with the autosomal dominant disorder familial hypercholesterolemia (FH) carry novel mutations in the low density lipoprotein receptor (LDLR) that is involved in cholesterol regulation. In different populations the spectrum of mutations identified is quite different and to date there have been only a few reports of the spectrum of mutations in FH patients from Pakistan. In order to identify the causative LDLR variants the gene was sequenced in a Pakistani FH family, while high resolution melting analysis followed by sequencing was performed in a panel of 27 unrelated sporadic hypercholesterolemia patients. In the family a novel missense variant (c.1916T > G, p.(V639G)) in exon 13 of LDLR was identified in the proband. The segregation of the identified nucleotide change in the family and carrier status screening in a group of 100 healthy subjects was done using restriction fragment length polymorphism analysis. All affected members of the FH family carried the variant and none of the non-affected members nor any of the healthy subjects. In one of the sporadic cases, two sequence changes were detected in exon 9, one of these was a recurrent missense variant (c.1211C > T; p.T404I), while the other was a novel substitution mutation (c.1214 A > C; N405T). In order to define the allelic status of this double heterozygous individual, PCR amplified fragments were cloned and sequenced, which identified that both changes occurred on the same allele. In silico tools (PolyPhen and SIFT) were used to predict the effect of the variants on the protein structure, which predicted both of these variants to have deleterious effect. These findings support the view that there will be a novel spectrum of mutations causing FH in patients with hypercholesterolaemia from Pakistan. PMID- 22311047 TI - Artemisia absinthium (AA): a novel potential complementary and alternative medicine for breast cancer. AB - Natural products have become increasingly important in pharmaceutical discoveries, and traditional herbalism has been a pioneering specialty in biomedical science. The search for effective plant-derived anticancer agents has continued to gain momentum in recent years. The present study aimed to investigate the role of crude extracts of the aerial parts of Artemisia absinthium (AA) extract in modulating intracellular signaling mechanisms, in particular its ability to inhibit cell proliferation and promote apoptosis in a human breast carcinoma estrogenic-unresponsive cell line, MDA-MB-231, and an estrogenic-responsive cell line, MCF-7. Cells were incubated with various concentrations of AA, and anti-proliferative activity was assessed by MTT assays, fluorescence microscopy after propidium iodide staining, western blotting and cell cycle analysis. Cell survival assays indicated that AA was cytotoxic to both MDA-MB-231 and MCF-7 cells. The morphological features typical of nucleic staining and the accumulation of sub-G1 peak revealed that the extract triggered apoptosis. Treatment with 25 MUg/mL AA resulted in activation of caspase-7 and upregulation of Bad in MCF-7 cells, while exposure to 20 MUg/mL AA induced upregulation of Bcl-2 protein in a time-dependent response in MDA-MB-231 cells. Both MEK1/2 and ERK1/2 was inactivated in both cell lines after AA treatment in a time-dependent manner. These results suggest that AA-induced anti-proliferative effects on human breast cancer cells could possibly trigger apoptosis in both cell lines through the modulation of Bcl-2 family proteins and the MEK/ERK pathway. This might lead to its possible development as a therapeutic agent for breast cancer following further investigations. PMID- 22311048 TI - Cell cycle arrest and apoptosis by expression of a novel TPIP (TPIP-C2) cDNA encoding a C2-domain in HEK-293 cells. AB - The human TPIP (TPTE and PTEN homologous Inositol lipid Phosphatase) belongs to the PTEN (Phosphatase and TENsin homologue deleted on chromosome 10) family of dual-specific phosphatases and is expressed from the human chromosome 13 as multiple splice-variants, e.g., TPIPalpha, beta, gamma mRNAs. PTEN is a well characterized tumor suppressor, which controls survival, adhesion, motility and migration of mammalian cells, its C2-domain plays crucial role in controlling these functions. However, role of isolated C2-domain protein in regulation of cell proliferation and apoptosis is not reported. We report sequence analysis and function of a novel human TPIP (TPIP-C2) cDNA encoding a 193 amino acid C2-domain in cell proliferation and apoptosis regulation. In silico analysis and homology modelling revealed that the C2-domain of TPIP-C2 is similar to that of PTEN but with short disorder sequences overlapping or adjacent to the post-translational modification sites. Overexpression of TPIP-C2 cDNA in human embryonic kidney (HEK 293) cells caused cell cycle arrest, inhibition of cell proliferation and induced apoptosis in an activated caspase 3 and PARP-dependent manner in comparison to overexpression of the full length human PTEN cDNA. TPIP-C2 overexpressed cells also showed S-phase cell cycle arrest. We suggest that C2-domain of TPIP-C2 may act as a dominant negative effector, which may bind to and arrest the cell proliferation signalling complex and isolated TPIP-C2-domain-like proteins expressed in mammalian cells/tissues may play important role in regulation of cell proliferation and apoptosis. The TPIP-C2 cDNA may be exploited for inducing cell cycle-inhibition and apoptosis in human cancer cells and tissues. PMID- 22311049 TI - Nearly complete mitochondrial genome of Polyascus gregaria and the phylogenetic relationships among maxillopodans. AB - We determined for the first time the nearly complete mitochondrial genome sequence of the entozoic Polyascus gregaria, a representative of Rhizocephala, Cirripedia. The nearly complete mitogenome was 15, 465 bp in length, consisting of 11 protein-coding genes, two rRNA genes, 22 tRNA genes and one major incomplete noncoding region. In total there are 73 overlapping nucleotides and 17 spacers between genes. All genes sequenced in P. gregaria mtDNA (including RNAs) were encoded on the same strand of the DNA, and the gene arrangement differed from that of other metazoan animals. The mitochondrial genome rearrangements included translocation of at least 8 genes and even inversion of the coding polarity of at least 2 genes. Comparative analysis of the gene orders with other maxillopodan mtDNAs showed that the unique characteristics of the thoracican cirripeds lineage were not observed in this representative of rhizocephalan. Phylogenetic analyses supported a close affinity of Rhizocephala to Thoracica. By adding the mitochondrial genomes from 4 copepods, the reciprocally monophyletic cirripeds and copepods clustered as sister groups, refusing the close relationship between Cirripedia and Remipedia. However, the monophyly of Maxillopoda was not supported in this study. PMID- 22311050 TI - Copper(I)-amine metallo-organocatalyzed synthesis of carbo- and heterocyclic systems. AB - The efficient and atom economical synthesis of 5-membered cyclic structures has been achieved through the combination of amino catalysis and metal catalysis. The discovery of a novel metallo-organocatalytic system merging the use of a catalytic copper(I) complex and a catalytic amount of cyclohexylamine allowed the room temperature preparation of a broad range of skeletons such as cyclopentanes, indanes, pyrrolidines and tetrahydrofuran, important structural cores of many biologically relevant molecules. Mechanistic studies were presented. PMID- 22311051 TI - IL-6 and IL-13 in induced sputum of COPD and asthma patients: correlation with respiratory tests. AB - BACKGROUND: IL-6 is strongly implicated in the development of chronic obstructive pulmonary disease (COPD). IL-13 is the well-documented central mediator in allergic asthma. IL-6 is attributed to the proinflammatory activities in COPD as well as asthma. In COPD patients exacerbation is increased by serum IL-6. The association of IL-13 as well as IL-6 with the impaired respiratory function of asthma patients remains controversial. OBJECTIVES: The aim of this study was to compare the concentration of IL-6 and IL-13 in the induced sputum of asthma and COPD patients, and to assess the possible association of these cytokines with the impairment of lung function. METHODS: Twenty-six subjects with COPD and 18 subjects with asthma were enrolled in this study. IL-6 and IL-13 levels were measured in induced sputum by ELISA and correlated with the results of respiratory tests. RESULTS: The induced sputum of COPD patients had a significantly higher IL-6 level than the sputum of asthma subjects while no significant differences were found in the levels of IL-13. There was a statistically significant negative correlation between IL-6 level and FEV(1) or FEV(1)/FVC in asthma patients (r = -0.59 and -0.54, respectively) and a negative correlation that did not reach statistical significance between IL-6 level and FEV(1), FEV(1)% or FVC in COPD subjects (r = -0.30, -0.30 and -0.38, respectively). There was no relationship between concentrations of IL-13 and impaired respiratory function. CONCLUSIONS: Our results confirmed that IL-6, but not of IL-13, is associated with respiratory disorders in both asthma and COPD patients. PMID- 22311052 TI - Targeted lymph node biopsy in mediastinoscopy using 3D FDG-PET/CT movies: a feasibility study. AB - In non-small-cell lung cancer, positive lymph nodes with increased fluorodeoxyglucose (FDG) uptake may be missed by mediastinoscopy. Lack of pathological confirmation may lead to radical, but unnecessary lung surgery. To minimize these false-negative results, the feasibility and potential value of three-dimensional (3D) FDG-PET/computed tomography (CT) movies were investigated to improve targeted lymph node biopsy during mediastinoscopies. PET/CT images were rendered in 3D volumes with multiplanar reconstructions and maximum intensity projections and reviewed in 3D 'fly-through' and 'fly-around' movies. These movies were developed and optimized by the Departments of Surgery and Nuclear Medicine. Twenty-two consecutive patients with non-small-cell lung cancer were included, of whom eight were FDG-PET positive for mediastinal lymph nodes. 3D FDG-PET/CT movies were presented to surgeons before mediastinoscopy. Surgical consequences were investigated, including sensitivity and the negative predictive value of mediastinoscopy. Results were compared with those of a retrospective study in which 3D techniques were not used. During mediastinoscopies, the 3D PET/CT movies were found to be helpful in the surgical localization of FDG positive lymph nodes. It led to more confidence in the surgical approach. The sensitivity and negative predictive value were 86 and 94%, respectively. Although not statistically significant, these results were higher compared with those of the retrospective study (75 and 92%, respectively). 3D FDG-PET/CT guidance during mediastinoscopy is feasible. The movies seem to lead to targeted biopsy of lymph nodes. They may reduce false-negative mediastinoscopies and improve staging of lung cancer. 3D FDG-PET/CT can be seen as a promising tool for further implementation of image-guided surgery. PMID- 22311053 TI - Lipase-embedded silica nanoparticles with oil-filled core-shell structure: stable and recyclable platforms for biocatalysts. AB - Lipase enzyme was embedded within silica nanoparticles with oil-filled core-shell structure. The enzyme embedded within such architecture retained all of its activity and showed high catalytic performance both in water and in organic media with optimal stability and recyclability. PMID- 22311054 TI - Agreement and reliability of functional performance and muscle power in patients with advanced osteoarthritis of the hip or knee. AB - OBJECTIVE: The purpose of this study was to test the reproducibility and clinical feasibility of three functional performance measures and five single-joint or multijoint muscle power measures. DESIGN: Twenty patients with a mean age of 68.7 +/- 7.2 yrs with severe hip or knee osteoarthritis were assessed for test-retest reliability and agreement on two occasions 1 wk apart. The outcomes were maximal single-joint muscle power (hip extension/abduction and knee extension/flexion), maximal muscle power during multijoint leg extension press, and functional performance measures (20-m walk, five-time repeated chair stands, and repeated unilateral knee bending). RESULTS: For single-joint and multijoint maximal peak power and functional performance measures, we demonstrated poor (CV(ws), approximately 25%, single-joint hip extension) and moderate (CV(ws), approximately 15%, multijoint leg extension press, single-joint knee extension, chair stands, and knee bending) to good (CV(ws), <10%, single-joint knee flexion, single-joint hip abduction, and 20-m walk) agreement and good (intraclass correlation coefficient, 0.61-0.80, single-joint hip extension, multijoint leg extension press, and knee bending) to excellent (intraclass correlation coefficient, >0.81, single-joint knee extension, knee flexion, hip abduction, 20 m walk, and chair stands) reliability. CONCLUSIONS: Isolated muscle power over the hip and knee can safely be evaluated with poor to good agreement and good to excellent reliability in patients with advanced hip or knee osteoarthritis. Functional performance and muscle power may be assessed concurrently. PMID- 22311055 TI - Changes in exercise capacity in subjects with cardiac asymptomatic hereditary hemochromatosis during a follow-up after 5 yrs. AB - OBJECTIVE: A long-term effect of hereditary hemochromatosis (HH) on aerobic exercise capacity (AEC) has not been well described. DESIGN: Forty-three HH and 21 volunteer control subjects who were asymptomatic underwent cardiopulmonary exercise testing using the Bruce protocol. AEC was assessed with minute ventilation (V(E)), oxygen uptake (V(O)(2)), and carbon dioxide production (V(CO)(2)) at baseline and at a follow-up assessment after 5 yrs. A paired t test was used for analyses of normality data; otherwise, Wilcoxon's signed rank-sum test was used. RESULTS: Thirty-three HH subjects and 18 volunteer control subjects returned for a repeat cardiopulmonary exercise testing at the fifth-year follow-up (80% overall return rate). At the fifth-year follow-up, AEC was not different between the two groups. Compared with baseline measurements, exercise time, peak V(O)(2), and the V(E)/V(CO)(2) slope did not differ statistically at the fifth-year follow-up between both groups. Iron depletion through phlebotomy for 5 yrs did not significantly affect AEC in newly diagnosed HH subjects at baseline (n = 14) and cardiac arrhythmias during exercise tended to decrease after 5 yrs of therapy in this group. CONCLUSIONS: The AEC of asymptomatic HH subjects treated using conventional therapy is not statistically affected by the disease during a 5-yr period. PMID- 22311056 TI - The effects of onabotulinum toxin A injection into rectus femoris muscle in hemiplegic stroke patients with stiff-knee gait: a placebo-controlled, nonrandomized trial. AB - OBJECTIVE: This study aimed to compare the efficacy of onabotulinum toxin A (onabot) injection into the rectus femoris muscle with that of placebo in the treatment of hemiplegic stroke patients presenting with stiff-knee gait. DESIGN: Twenty-five chronic hemiparetic stroke patients presenting with a stiff-knee gait were included in this study. Fifteen patients received 100-125 U of onabot, and 10 patients received placebo into the rectus femoris muscle. Three-dimensional gait analysis, energy expenditure, 10-m and 6-min walk tests, and spasticity level of the rectus femoris were evaluated at baseline and 2 mos posttreatment. RESULTS: The mean age of patients who received onabot was 53.86 +/- 14.74 yrs and of those who received placebo was 59.00 +/- 8.11 yrs. At study onset, groups were similar with respect to all parameters (P > 0.05). We observed significant improvement in knee flexion (7 degrees average) during swing and a reduction in energy cost of 0.8-J/kg per meter response to injection of 100-125 U of onabot into the rectus femoris muscle. Onabot treatment significantly reduced muscle tone and improved knee kinematics, energy expenditure during walking, and functional assessments at 2 mos (P < 0.05); however, placebo had no effects on these parameters. Moreover, maximum knee flexion at swing and energy expenditure in the onabot group was significantly better than placebo at 2 mos (P < 0.05). CONCLUSIONS: Our results showed the superiority of onabot over placebo in increasing knee flexion during swing phase and decreasing energy expenditure. The application of onabot into the rectus femoris muscle in stroke patients who presented with stiff-knee gait may be a treatment option to provide independent, safe, and less tiring ambulation. PMID- 22311057 TI - Cognitive impairments and depressive symptoms did not impede upper limb recovery in a clinical repetitive task practice program after stroke: a pilot study. AB - OBJECTIVE: We examined whether cognitive impairments or depressive symptoms impeded improvement in upper limb function in a clinical repetitive task practice program. DESIGN: Participants had mild to moderate upper limb impairment after stroke (n = 20). We characterized baseline cognitive function and depressive symptoms using the Repeatable Battery of Neuropsychological Status and the Hamilton Rating Scale for Depression. We measured upper limb function at baseline, week 4, and week 24 using the Action Research Arm Test. RESULTS: Participants with and without cognitive impairments improved significantly over time (F(1,17) = 84.48, P < 0.001) regardless of cognitive status (t(31) = 1.42, P = 0.16) or time since stroke (t(17) = 0.07, P = 0.95). Participants with and without depressive symptoms improved significantly over time (F(1,18) = 86.29, P < 0.001), but participants with depressive symptoms demonstrated greater improvement than did participants with no depressive symptoms (t(31) = 3.19, P = 0.003), regardless of time since stroke (t(17) = 0.06, P = 0.95). CONCLUSIONS: Preliminary findings suggest that cognitive impairments and depressive symptoms may not impede benefit from repetitive task practice after stroke. PMID- 22311058 TI - Does race influence functional outcomes in patients with acute stroke undergoing inpatient rehabilitation? AB - OBJECTIVE: Race has been shown to affect stroke-related morbidity and mortality. The purpose of this study was to determine the influence of race on rehabilitation functional outcomes in patients with an acute stroke admitted to a designated stroke rehabilitation unit. DESIGN: A 2-yr prospective study was conducted of 670 patients admitted to an acute stroke rehabilitation unit within 30 days after an acute stroke. Demographic data along with admission and discharge Functional Independence Measure scores were recorded in a computerized stroke database. Patients participated in a standardized rehabilitation program 5 days a week for a length of stay dependent upon their individual needs. RESULTS: The distribution of patients by race was 504 whites, 115 blacks, 38 Hispanics, and 13 Asians. The mean age of the study population was 70 yrs. Whites had a higher prevalence of atrial fibrillation, and blacks, Hispanics, and Asians had a higher prevalence of hypertension and diabetes mellitus. The primary and secondary functional rehabilitation outcomes were similar for all four groups after similar intensity of therapy (3.5 hrs daily). CONCLUSIONS: This study suggests that race does not influence rehabilitation functional outcomes in patients with acute stroke undergoing rehabilitation for the same intensity of therapy if admitted soon after their acute stroke. PMID- 22311059 TI - Analgesic effect of transcutaneous electrical nerve stimulation after laparoscopic cholecystectomy. AB - OBJECTIVE: This study aimed to assess the effect of Transcutaneous Electrical Nerve Stimulation (TENS) on pain, nausea, and emesis in patients submitted to surgery for laparoscopic cholecystectomy. DESIGN: A clinical single-masked randomized study assessed patients submitted to laparoscopic cholecystectomy, who were divided into two groups: placebo TENS (G1) and active TENS (G2). The intensity of pain was determined using the visual analog scale and the 11-point Verbal Numerical Scale, applied to the participants before (M1) and 30 mins after (M2) TENS. A conventional biphasic square pulse TENS current was used, at a frequency of 150 Hz and a pulse width of 75 MUsecs. The relative risks of the occurrence of nausea and emesis were calculated for groups G1 and G2. Determination of the effect of TENS on analgesia used the Mann-Whitney U test, at a significance level of 5%, to compare independent samples (Dif G1 and Dif G2). RESULTS: The relative risk of nausea and/or emesis was 2.17 times greater for patients from the placebo group. Pain evaluation using the visual analog scale showed median differences between M1 and M2 of 0.4 and 2.4 for groups G1 and G2, respectively. The values obtained using Verbal Numerical Scale were 0.7 (G1) and 3.0 (G2). The active TENS significantly reduced postoperative pain compared with the placebo (P < 0.016). CONCLUSIONS: Active TENS promoted significant postoperative pain relief, and fewer complaints of nausea and emesis, in patients submitted to laparoscopic cholecystectomy surgery. PMID- 22311060 TI - The effect of walking in high- and low-heeled shoes on erector spinae activity and pelvis kinematics during gait. AB - OBJECTIVE: Wearing high-heeled shoes may produce deleterious effects on the musculoskeletal system. The purpose of this study was to evaluate the changes in electromyographic (EMG) activity of the erector spinae muscles and pelvis kinematics during gait while wearing low- and high-heeled shoes in both young and middle-aged adult women. DESIGN: In 31 young women (20-25 yrs) and 15 middle-aged women (45-55 yrs) without back pain, the EMG activity of the erector spinae muscle and pelvis kinematics in the sagittal, frontal, and transverse planes were assessed during gait on flat surface at natural speeds in three conditions: without shoes and in low- (4 cm) and high- (10 cm) heeled shoes. RESULTS: In younger women, significant differences in lumbar erector spinae EMG activity were observed during gait at initial ground contact as well as in toe off between the three conditions, with an increasing amount of EMG activity being observed in association with increased heel height. In middle-aged women, significantly higher lumbar erector spinae EMG activity was noted during gait with high-heeled shoes compared with gait without shoes. Interestingly, younger women exhibited an increase in pelvic range of motion in the sagittal plane during high-heeled gait compared with low-heeled gait and walking without shows; however, this compensatory response was not observed in middle-aged women. CONCLUSIONS: From a clinical perspective, increased lumbar erector spinae muscle activity associated with wearing high-heeled shoes could exacerbate muscle overuse and lead to low back problems. The lower pelvic range of motion associated with wearing high heels in middle-aged women may indicate that tissues in the lumbopelvic region become more rigid with age and that the harmful effect of high-heeled shoes on posture and spinal tissues may be more pronounced with advancing age. PMID- 22311061 TI - Men recover ability to function less than women do: an observational study of 1094 subjects after hip fracture. AB - OBJECTIVE: The aim of this study was to investigate the association between sex and functional outcome after acute inpatient rehabilitation in hip-fracture patients. DESIGN: We investigated 1094 of 1186 people admitted consecutively to our rehabilitation hospital because of a hip fracture. Functional outcome was assessed using Barthel Index scores. Barthel Index efficiency (improvement per day of stay length) and Barthel Index effectiveness (proportion of potential improvement achieved) were calculated. RESULTS: The median Barthel Index score at discharge from inpatient rehabilitation was 85 in the 970 women and 75 in the 124 men (interquartile range, 65-95 in women and 60-95 in men, P = 0.001). Both Barthel Index efficiency and effectiveness were significantly lower in men (P = 0.030 and P = 0.007, respectively). After adjustment for six confounders, we confirmed that men had lower Barthel Index scores (P = 0.030), Barthel Index efficiency (P = 0.024), and Barthel Index effectiveness (P = 0.040). The risk of achieving a low Barthel Index score (i.e., <85) at the end of acute inpatient rehabilitation was higher for men than for women (adjusted odds ratio, 2.055; 95% CI, 1.212-3.483; P = 0.007). CONCLUSIONS: In our large sample of hip-fracture patients, men had a significantly worse functional outcome than did women after acute inpatient rehabilitation. PMID- 22311062 TI - Motorcycle for persons with disabilities. PMID- 22311063 TI - Myasthenia gravis and endurance exercise. AB - This is the first report of a runner with myasthenia gravis who completed an ultra endurance event. Myasthenia gravis, a neuromuscular disease that usually results in skeletal muscle weakness, which worsens with exercise and strenuous aerobic exercise, is generally contraindicated. Our runner completed a 220-km, 5 day ultramarathon and presented with various symptoms including muscular skeletal weakness, cramps, generalized fatigue, unintelligible speech, involuntary eye and mouth movements, problems swallowing, food lodging in his throat, and problems breathing. Risk factors identified for exacerbations are running in extreme temperatures, prolonged runs (especially a distance of 30 km or more), running uphill, lack of sleep, and stress. The medical team was in the novel situation to look after a runner with myasthenia gravis and needed to be aware of the patient's condition, symptoms, and risk factors to safely care for him. PMID- 22311065 TI - On the probability of random genetic mutations for various types of tumor growth. AB - In this work, we consider the problem of estimating the probability for a specific random genetic mutation to be present in a tumor of a given size. Previous mathematical models have been based on stochastic methods where the tumor was assumed to be homogeneous and, on average, growing exponentially. In contrast, we are able to obtain analytical results for cases where the exponential growth of cancer has been replaced by other, arguably more realistic types of growth of a heterogeneous tumor cell population. Our main result is that the probability that a given random mutation will be present by the time a tumor reaches a certain size, is independent of the type of curve assumed for the average growth of the tumor, at least for a general class of growth curves. The same is true for the related estimate of the expected number of mutants present in a tumor of a given size, if mutants are indeed present. PMID- 22311064 TI - SIRT1 modulates MAPK pathways in ischemic-reperfused cardiomyocytes. AB - SIRT1, an ubiquitous NAD(+)-dependent deacetylase that plays a role in biological processes such as longevity and stress response, is significantly activated in response to reactive oxygen species (ROS) production. Resveratrol (Resv), an important activator of SIRT1, has been shown to exert major health benefits in diseases associated with oxidative stress. In ischemia-reperfusion (IR) injury, a major role has been attributed to the mitogen-activated protein kinase (MAPK) pathway, which is upregulated in response to a variety of stress stimuli, including oxidative stress. In neonatal rat ventricular cardiomyocytes subjected to simulated IR, the effect of Resv-induced SIRT1 activation and the relationships with the MAPK pathway were investigated. Resv-induced SIRT1 overexpression protected cardiomyocytes from oxidative injury, mitochondrial dysfunction, and cell death induced by IR. For the first time, we demonstrate that SIRT1 overexpression positively affects the MAPK pathway-via Akt/ASK1 signaling-by reducing p38 and JNK phosphorylation and increasing ERK phosphorylation. These results reveal a new protective mechanism elicited by Resv induced SIRT1 activation in IR tissues and suggest novel potential therapeutic targets to manage IR-induced cardiac dysfunction. PMID- 22311066 TI - An approach to therapeutic agents through selective targeting of destabilised nucleic acid duplex sequences. AB - The binding of DeltaDelta/LambdaLambda-[{Ru(phen)(2)}(2)(MU-bb(n))](4+) {where phen = 1,10-phenanthroline, bb(n) = 1,n-bis[4(4'-methyl-2,2'-bipyridyl)]-alkane (DeltaDelta/LambdaLambda-Rubb(n))} to the non-self complementary oligonucleotide 5'-d(CGCGATAAGCCGC.5'-GCGGCATTACGCG) (3-DB) has been examined using a 4',6 diamidino-2-phenylindole dihydrochloride (DAPI) displacement assay. The 3-DB oligonucleotide contains two single adenine bulge nucleotides that are separated by three base pairs. (1)H NMR spectroscopy data demonstrated that the adenine bases are intra-helical and that the segment containing the two bulge nucleotides and the three A.T base pairs between the bulges forms a destabilised segment within the stable duplex oligonucleotide. The DAPI displacement assay demonstrated that DeltaDelta-Rubb(7)-bound 3-DB with higher affinity than the other members of the DeltaDelta/LambdaLambda-Rubb(n) series. Molecular models suggested that the seven-carbon chain length in DeltaDelta-Rubb(7) was ideal to span the distance between the two bulge sites. The binding of DeltaDelta-Rubb(7) to 3-DB was also studied by (1)H NMR spectroscopy and molecular modelling. The selective changes in chemical shifts for the resonances from 3-DB upon addition of DeltaDelta-Rubb(7) suggested that the metal complex specifically bound at the destabilised segment between A(5) and A(19). Observation in NOESY spectra of NOE cross peaks between 3-DB and DeltaDelta-Rubb(7) confirmed that one of the ruthenium centres bound at the A(5) bulge site, with the other metal centre positioned at the A(19) bulge. In addition, DeltaDelta-Rubb(7) was found to bind chromosomal DNA extracted from a suspension of Staphylococcus aureus that had been incubated with the ruthenium(ii) complex. As inert dinuclear ruthenium(ii) complexes are capable of being transported into a bacterial cell and bind chromosomal DNA, it is possible that they could be developed into anti-microbial agents that specifically target destabilised segments of DNA that are recognised by essential DNA-binding proteins. PMID- 22311067 TI - Light harvesting zinc naphthalocyanine-perylenediimide supramolecular dyads: long lived charge-separated states in nonpolar media. AB - Photoinduced electron-transfer dynamics of self-assembled donor-acceptor dyads formed by axial coordination of zinc naphthalocyanine, ZnNc, and perylenediimide (PDI) bearing either pyridine (py) or imidazole (im) coordinating ligands were investigated. The PDIim unit was functionalized with tert-octylphenoxy groups at the bay positions, which avoid aggregation providing solubility, to examine the effect of the bulky substituents at the bay positions on the rates of electron transfer reactions. The combination between zinc naphthalocyanine and perylenediimide entities absorbs light over a wide region of the visible and near infrared (NIR) spectrum. The binding constants of the self-assembled ZnNc:PDIpy (1) and ZnNc:PDIim (2) in toluene were found to be 2.40 * 10(4) and 1.10 * 10(5) M(-1), respectively, from the steady-state absorption and emission measurements, indicating formation of moderately stable complexes. The geometric and electronic calculations by using an ab initio B3LYP/6-311G method showed the majority of the highest occupied frontier molecular orbital (HOMO) on the zinc naphthalocyanine entity, while the lowest unoccupied molecular orbital (LUMO) was on the perylenediimide entities, suggesting that the charge-separated states of the supramolecular dyads are ZnNc(+):PDI(-). The electrochemical results suggest the exothermic charge-separation process via the singlet states of both ZnNc and PDI entities in nonpolar toluene. Upon coordination of perylenediimide to ZnNc, the main quenching pathway involved charge separation via the singlet-excited states of ZnNc and PDIs. Clear evidence of the intramolecular electron transfer from the singlet-excited state of ZnNc to PDI within the supramolecular dyads in toluene was monitored by the femtosecond laser photolysis by observing the characteristic absorption band of the PDI radical anion (PDI(-)) and the ZnNc radical cation (ZnNc(+)) in the visible and NIR regions. The rate constants of charge-separation (k(CS)) processes of the self-assembled dyads 1 and 2 were determined to be 4.05 * 10(10) and 1.20 * 10(9) s(-1), respectively. The rate constant of charge recombination (k(CR)) and the lifetime of charge-separated states (tau(CS)) of dyad 1 were determined to be 2.34 * 10(8) s(-1) and 4.30 ns, respectively. Interestingly, a slower charge recombination (2.20 * 10(7) s(-1)) and a longer lifetime of the charge separated state (45 ns) were observed in dyad 2 in nonpolar toluene by utilizing the nanosecond transient measurements. The absorption in a wide section of the solar spectrum and the high charge separation/charge-recombination ratio suggest the usefulness of the self assembled zinc naphthalocyanine-perylenediimide dyads as good photosynthetic models. PMID- 22311068 TI - Metal ion dependency of serine racemase from Dictyostelium discoideum. AB - D-Serine is known to act as an endogenous co-agonist of the N-methyl-D-aspartate receptor in the mammalian brain and is endogenously synthesized from L-serine by a pyridoxal 5'-phosphate-dependent enzyme, serine racemase. Though the soil living mycetozoa Dictyostelium discoideum possesses no genes homologous to that of NMDA receptor, it contains genes encoding putative proteins relating to the D serine metabolism, such as serine racemase, D-amino acid oxidase, and D-serine dehydratase. D. discoideum is an attractive target for the elucidation of the unknown functions of D-serine such as a role in cell development. As part of the elucidation of the role of D-serine in D. discoideum, we cloned, overexpressed, and examined the properties of the putative serine racemase exhibiting 46% amino acid sequence similarity with the human enzyme. The enzyme is unique in its stimulation by monovalent cations such as Na(+) in addition to Mg(2+) and Ca(2+), which are well-known activators for the mammalian serine racemase. Mg(2+) or Na(+) binding caused two- to ninefold enhancement of the rates of both racemization and dehydration. The half-maximal activation concentrations of Mg(2+) and Na(+) were determined to be 1.2 MUM and 2.2 mM, respectively. In the L serine dehydrase reaction, Mg(2+) and Na(+) enhanced the k (cat) value without changing the K (m) value. Alanine mutation of the residues E207 and D213, which correspond to the Mg(2+)-binding site of Schizosaccharomyces pombe serine racemase, abolished the Mg(2+)- and Na(+)-dependent stimulation. These results suggest that Mg(2+) and Na(+) share the common metal ion-binding site. PMID- 22311069 TI - Very short bouts of non-exercise physical activity associated with metabolic syndrome under free-living conditions in Japanese female adults. AB - To assess the association between very short daily non-exercise physical activity (PA) lasting <5 min and metabolic syndrome (MS). A total of 42 females (50 +/- 6 years) wore a pedometer with a one-axial accelerometer (Lifecorder, Kenz, Japan) to determine the time and the frequency of PA and the moderate to vigorous intensity PA (MVPA). In addition to the PA and the MVPA (PA(all) and MVPA(all)), the PA and MVPA were analyzed based on the bout duration, such as >32 s, >1 min, >3 min, and >5 min (PA(32S), PA(1M), PA(3M), PA(5M); MVPA(32S), MVPA(1M), MVPA(3M), MVPA(5M)). MS was defined according to the Japanese standard based on waist circumfluence, blood lipids, blood glucose, and blood pressure. The frequency of the MVPA(1M) was significantly lower in subjects with MS compared with that in subjects without MS (P < 0.05). The frequency of MVPA(32S) and MVPA(1M) was significantly associated with the HDL cholesterol (P < 0.05). The frequency of PA(3M) and PA(5M) was significantly associated with the fasting glucose level (P < 0.05). In contrast, we could not find any significant relationships between MS and the components of MS and the frequency of PA lasting <32 s. These results demonstrated that very short non-exercise PA, such as MVPA lasting >32 s to 3 min, has significantly associated with the components of MS. The specific advantages with regard to PA lasting <32 s remain unclear. PMID- 22311070 TI - Sterilization with electron beam irradiation influences the biomechanical properties and the early remodeling of tendon allografts for reconstruction of the anterior cruciate ligament (ACL). AB - Although allografts for anterior cruciate ligament (ACL) replacement have shown advantages compared to autografts, their use is limited due to the risk of disease transmission and the limitations of available sterilization methods. Gamma sterilization has shown detrimental effects on graft properties at the high doses required for sufficient pathogen inactivation. In our previous in vitro study on human patellar tendon allografts, Electron beam (Ebeam) irradiation showed less detrimental effects compared to gamma sterilization (Hoburg et al. in Am J Sports Med 38(6):1134-1140, 2010). To investigate the biological healing and restoration of the mechanical properties of a 34 kGy Ebeam treated tendon allograft twenty-four sheep underwent ACL replacement with either a 34 kGy Ebeam treated allograft or a non-sterilized fresh frozen allograft. Biomechanical testing of stiffness, ultimate failure load and AP-laxity as well as histological analysis to investigate cell, vessel and myofibroblast-density were performed after 6 and 12 weeks. Native sheep ACL and hamstring tendons (HAT, each n = 9) served as controls. The results of a previous study analyzing the remodeling of fresh frozen allografts (n = 12) and autografts (Auto, n = 18) with the same study design were also included in the analysis. Statistics were performed using Mann-Whitney U test followed by Bonferroni-Holm correction. Results showed significantly decreased biomechanical properties during the early remodeling period in Ebeam treated grafts and this was accompanied with an increased remodeling activity. There was no recovery of biomechanical function from 6 to 12 weeks in this group in contrast to the results observed in fresh frozen allografts and autografts. Therefore, high dose Ebeam irradiation investigated in this paper cannot be recommended for soft tissue allograft sterilization. PMID- 22311071 TI - Excited-state proton transfer in N-methyl-6-hydroxyquinolinium salts: solvent and temperature effects. AB - The excited-state proton transfer (ESPT) reaction of the "super"photoacid N methyl-6-hydroxyquinolinium (MHQ) was studied using both fluorescence upconversion and time-correlated single photon counting (TCSPC) techniques. The ultrafast ESPT kinetics were investigated in various alcohols and water and determined to be solvent-controlled. The ESPT temperature dependence of MHQ was also studied in various alcohols and compared to that observed for another "super"photoacid, 5,8-dicyano-2-naphthol (DCN2). A full set of kinetic and thermodynamic parameters describing the ESPT was obtained. The protolytic photodissociation rate constant for MHQ was higher than that for DCN2, while the ESPT activation energies of MHQ were smaller. These findings are attributed to the approximately 3 orders of magnitude differences in excited-state acidities of MHQ and DCN2. PMID- 22311072 TI - The diet of wild black-fronted titi monkeys Callicebus nigrifrons during a bamboo masting year. AB - Black-fronted titi monkeys, Callicebus nigrifrons, are endemic primates of the Atlantic forest of Brazil, and little is known about their diet and how it is affected by seasonal changes. The aim of this study is to analyze the diet of C. nigrifrons during a bamboo masting year. This study was conducted in the reserve RPPN Santuario do Caraca, MG, and the collection of data was carried out from January 2007 to January 2008 through monthly campaigns. The feeding behaviour of four habituated groups in the same forest fragment was observed. The data were collected through focal animal observations of 10 min each with instantaneous recording of behaviour every 30 s, totalling 220.5 h of observations during 71 field days. The diet of groups consisted of 43.4% fruit, 37.0% seeds, 8.2% leaves, 6.2% flowers, 2.5% animal matter and 2.7% non-identified/other items. At least 51 species of plants were consumed. More than half of the diet comprised only five species: Merostachys fischeriana (bamboo, 32.3%), Solanum cinnamomum (nightshade, 8.7%), Vitex spp. (Lamiaceae, 4.5%), Casearia decandra (wild honeytree, 3.8%) and Amaioua guianensis (woody dioecious species, 3.7%). According to the values obtained from Levins' index analysis (0.05-0.28) our subjects had a narrow diet width. The individuals in this study were able to incorporate significant amounts of bamboo seeds in their diet, and this was inversely related to fruit consumption. In conclusion, C. nigrifrons was able to amply exploit a bamboo masting event, which generated a narrow diet width. PMID- 22311073 TI - Four strategies for water transfer of oil-soluble near-infrared-emitting PbS quantum dots. AB - The successful transfer of oil-soluble quantum dots (QDs) into water is critical for many of their bioapplications. In this paper, the impacts of four various strategies (i.e., via micelles, nanohydrogels, amphiphilic polymers and water soluble thiol small molecules) on the phase transfer of oil-soluble oleic acid capped NIR-emitting PbS QDs into water were evaluated systematically. It was found that the process of water transfer and the optical property of the resulting water-soluble QDs highly hinge on the type of the phase transfer agents used due to their different interactions with QD surface. Among all these phase transfer agents, SOC micelles and glutathione (thiol) molecules are more favorable for retaining the optical property of the initial oil-soluble PbS QDs. As a result, the obtained water-soluble QDs show strong NIR fluorescence (PL QY > 30% in water). However, in the case of nanohydrogel and amphiphilic polymers, the corresponding water-soluble ones display relatively weak fluorescence emission. These results suggest fully that "correct" phase transfer agents should be selected in order to obtain high-quality water-soluble PbS QDs. The possible reasons for this obvious difference were further analyzed and revealed. Besides, the preliminary results obtained also indicate that the NIR-emitting PbS QDs will be a potential probe in the in vivo biomedical imaging of small animals. PMID- 22311074 TI - PEG-based bioresponsive hydrogels with redox-mediated formation and degradation. AB - A hydrogel which will undergo macroscopic transition responding to redox stimuli is prepared. Mercapto precursors are prepared from 4-armed polyethylene glycol and after deprotection of thiolate anions, they can transform into disulfide crosslinked hydrogels within 3 min by responding to oxidant H(2)O(2). Desirable elasticity is exhibited with a wide range of storage modulus from 50 Pa to 14 kPa through rheological investigation. In addition, the hydrogels are found to be hydrolytically stable but degrade within 75 days when exposed to reductant such as glutathione (GSH). So gelation time and degradation behavior can be regulated by concentrations of precursor, oxidant, reductant, temperature, and pH value. Notably, interest arises from the long-period degradation under low GSH concentration of 0.01 mM that is similar to extracellular level, but not the fast disintegration under high concentration intracellular, providing the possibility of "smart" degradation responding to those cell-secreted biomacromolecules during the process of tissue regeneration. Furthermore, both hydrogels and their degradation products show cell viability above 90% culturing with C2C12 cells, representing nontoxic properties. Such a stimuli-responsive degradation strategy will give promising application in tissue repair and regeneration; especially enable the achievement of matching the degradation kinetics with physiological environment. PMID- 22311075 TI - Application of K/Sr co-doped calcium polyphosphate bioceramic as scaffolds for bone substitutes. AB - Ion doping is one of the most important methods to modify the properties of bioceramics for better biodegrade abilities, biomechanical properties, and biocompatibilities. This paper presents a novel ion doping method applied in calcium polyphosphate (CPP)-based bioceramic scaffolds substituted by potassium and strontium ions (K/Sr) to form (K/Sr-CPP) scaffolds for bone tissue regeneration. The microstructure and crystallization of the scaffolds were detected by scanning electron microscopy and X-ray diffraction. Compressive strength and degradation tests were assessed to evaluate the mechanical and chemical stabilities of K/Sr-CPP in vitro. The cell biocompatibility was measured with respect to the cytotoxicity of the extractions of scaffolds. Muscle pouches and bone implantation were performed to evaluate the biodegradability and osteoconductivity of the scaffolds. The results indicated that the obtained K/Sr CPP scaffolds had a single beta-CPP phase. The unit cell volume and average grain size increased but the crystallization decreased after the ions were doped into the CPP structure. The K/Sr-CPP scaffolds yielded a higher compressive strength and a better degradation property than the pure CPP scaffold. The MTT assay and in vivo results reveal that the K/Sr-CPP scaffolds exhibited a better cell biocompatibility and a tissue biocompatibility than CPP and hydroxyapatite scaffolds. This study proves the potential applications of K/Sr-CPP scaffolds in bone repair. PMID- 22311076 TI - The healing of critical-size calvarial bone defects in rat with rhPDGF-BB, BMSCs, and beta-TCP scaffolds. AB - Platelet-derived growth factor-BB (PDGF-BB) plays important roles in regenerating damaged tissue. In this study we investigated the effects of a tissue-engineered bone combined with recombinant human PDGF-BB (rhPDGF-BB), bone marrow stem cells (BMSCs) and beta-tricalcium phosphate (beta-TCP) to repair critical-size calvarial bone defects in rat. Proliferation and osteogenic differentiation of BMSCs treated with different concentration rhPDGF-BB (0, 10, and 50 ng/ml) was evaluated by MTT, alkaline phosphatase (ALP) activity, alizarin red staining and real-time quantitative PCR (RT-qPCR) analysis of osteogenic gene. BMSCs were then combined with rhPDGF-BB-loaded beta-TCP and transplanted into 5 mm calvarial bone defects. The new bone formation and mineralization was evaluated by micro computerized tomography (Micro-CT) and histological analysis at week 8 after operation. It was observed that the proliferation of BMSCs treated with rhPDGF-BB was enhanced with a time- and dose- dependent manner. There were increased ALP activity, mineralized deposition and elevated mRNA levels of osteogenic gene for BMSCs treated with rhPDGF-BB, particularly in the 50 ng/ml group. Histological analysis showed new bone formation and mineralization in the rhPDGF-BB/BMSCs/beta TCP group was significantly higher than BMSCs/beta-TCP, rhPDGF-BB/beta-TCP, and beta-TCP alone group (P < 0.05). In conclusion, rhPDGF-BB/BMSCs/beta-TCP is a promising tissue-engineered bone for craniofacial bone regeneration. PMID- 22311077 TI - Development of chitosan-tripolyphosphate non-woven fibrous scaffolds for tissue engineering application. AB - The fibrous scaffolds are promising for tissue engineering applications because of their close structural resemblance with native extracellular matrix. Additionally, the chemical composition of scaffold is also an important consideration as they have significant influences on modulating cell attachment, morphology and function. In this study, chitosan-tripolyphosphate (TPP) non-woven fibrous scaffolds were prepared through wetspinning process. Interestingly, at physiological pH these scaffolds release phosphate ions, which have significant influences on cellular function. For the first time, cell viability in presence of varying concentration of sodium TPP solution was analyzed and correlated with the phosphate release from the scaffolds during 30 days incubation period. In vitro degradation of the chitosan-TPP scaffolds was higher than chitosan scaffolds, which may be due to decrease in crystallinity as a result of instantaneous ionic cross-linking during fiber formation. The scaffolds with highly interconnected porous structure present a remarkable cytocompatibility for cell growing, and show a great potential for tissue engineering applications. PMID- 22311078 TI - In vitro corrosion behaviour of Ti-Nb-Sn shape memory alloys in Ringer's physiological solution. AB - The nearly equiatomic Ni-Ti alloy (Nitinol) has been widely employed in the medical and dental fields owing to its shape memory or superelastic properties. The main concern about the use of this alloy derives form the fact that it contains a large amount of nickel (55% by mass), which is suspected responsible for allergic, toxic and carcinogenic reactions. In this work, the in vitro corrosion behavior of two Ti-Nb-Sn shape memory alloys, Ti-16Nb-5Sn and Ti-18Nb 4Sn (mass%) has been investigated and compared with that of Nitinol. The in vitro corrosion resistance was assessed in naturally aerated Ringer's physiological solution at 37 degrees C by corrosion potential and electrochemical impedance spectroscopy (EIS) measurements as a function of exposure time, and potentiodynamic polarization curves. Corrosion potential values indicated that both Ni-Ti and Ti-Nb-Sn alloys undergo spontaneous passivation due to spontaneously formed oxide film passivating the metallic surface, in the aggressive environment. It also indicated that the tendency for the formation of a spontaneous oxide is greater for the Ti-18Nb-5Sn alloy. Significantly low anodic current density values were obtained from the polarization curves, indicating a typical passive behaviour for all investigated alloys, but Nitinol exhibited breakdown of passivity at potentials above approximately 450 mV(SCE), suggesting lower corrosion protection characteristics of its oxide film compared to the Ti-Nb-Sn alloys. EIS studies showed high impedance values for all samples, increasing with exposure time, indicating an improvement in corrosion resistance of the spontaneous oxide film. The obtained EIS spectra were analyzed using an equivalent electrical circuit representing a duplex structure oxide film, composed by an outer and porous layer (low resistance), and an inner barrier layer (high resistance) mainly responsible for the alloys corrosion resistance. The resistance of passive film present on the metals' surface increases with exposure time displaying the highest values to Ti-18Nb-4Sn alloy. All these electrochemical results suggest that Ti-Nb-Sn alloys are promising materials for biomedical applications. PMID- 22311079 TI - Sol-gel method to fabricate CaP scaffolds by robocasting for tissue engineering. AB - Highly porous calcium phosphate (CaP) scaffolds for bone-tissue engineering were fabricated by combining a robocasting process with a sol-gel synthesis that mixed Calcium Nitrate Tetrahydrate and Triethyl Phosphite precursors in an aqueous medium. The resulting gels were used to print scaffolds by robocasting without the use of binder to increase the viscosity of the paste. X-ray diffraction analysis confirmed that the process yielded hydroxyapatite and beta-tricalcium phosphate biphasic composite powders. Thus, the scaffold composition after crystallization of the amorphous structure could be easily modified by varying the initial Ca/P ratio during synthesis. The compressive strengths of the scaffolds are ~6 MPa, which is in the range of human cancellous bone (2-12 MPa). These highly porous scaffolds (~73 vol% porosity) are composed of macro-pores of ~260 MUm in size; such porosity is expected to enable bone ingrowth into the scaffold for bone repair applications. The chemistry, porosity, and surface topography of such scaffolds can also be modified by the process parameters to favor bone formation. The studied sol-gel process can be used to coat these scaffolds by dip-coating, which induces a significant enhancement of mechanical properties. This can adjust scaffold properties such as composition and surface morphology, which consequently may improve their performances. PMID- 22311080 TI - Recent advances in the stereoselective synthesis of carbohydrate 2-C-analogs. AB - C-branched carbohydrates are of current interest for glycochemistry, are widely found in nature and serve as important subunits in many antibiotics, bacterial polysaccharides and macrolides. Among C-functionalized saccharides, 2-C-branched carbohydrates represent challenging structures for synthetic chemists, since in contrast to C-glycosides they are not easily accessible from glycosyl bromides or other simple precursors. In this perspective we want to summarize recent approaches to 2-C-branched carbohydrates over the past fifteen years. The two main strategies are based on ring-opening of 1,2-cyclopropanated carbohydrates by various reagents, as well as radical additions to glycals and further transformations, developed in our group. Both methods are characterized by high stereoselectivities and good yields and give access to a broad variety of functionalized carbohydrate 2-C-analogs. PMID- 22311081 TI - New drugs 2012 part I. PMID- 22311082 TI - Effects of taurine-magnesium coordination compound on ionic channels in rat ventricular myocytes of arrhythmia induced by ouabain. AB - Taurine-magnesium coordination compound (TMCC) has anti-arrhythmic effects. The aim of the present study was to explore the targets of the anti-arrhythmic effect of TMCC and the electrophysiological effects of TMCC on ouabain-induced arrhythmias in rat ventricular myocytes. Sodium current (I(Na)), L-type calcium current (I(ca, L)), and transient outward potassium current (I(to)) were measured and analyzed using whole-cell patch-clamp recording technique in normal rat cardiac myocytes and rat ventricular myocytes of arrhythmia induced by ouabain. In isolated ventricular myocytes, I(Na) and I(to) were blocked by TMCC (100, 200, 400 MUM) in a concentration-dependent manner, and the effects of TMCC (400 MUM) were equal to that of amiodarone. However, I (ca, L) was moderately increased by TMCC (400 MUM) while significantly decreased by amiodarone. Ouabain (5 MUM) significantly decreased sodium, L-type calcium, and transient outward potassium currents. TMCC (100 MUM) relieved abnormal sodium currents induced by ouabain through facilitation of steady-state inactivation. TMCC (200 and 400 MUM) relieved abnormal L-type calcium currents induced by ouabain through facilitation of steady-state activation and retardation of steady-state inactivation. TMCC failed to further inhibit abnormal transient outward potassium currents induced by ouabain. However, amiodarone inhibited the decreasing sodium, L-type calcium, and transient outward potassium currents further. These data suggest that I(Na), I(ca, L), and I(to) may be the targets of the antiarrhythmic effect of TMCC, which can antagonize ouabain-induced changes of ionic currents in rat ventricular myocytes. PMID- 22311083 TI - Combined influence of intermittent exercise and temperature stress on the modulation of fluoride toxicity. AB - Regardless of the circumstantial evidences on the involvement of fluoride on the etiology and pathogenesis of fluorosis, several lines of evidences strongly indicate the influence of modulator factors such as duration of fluoride exposure, age, temperature, and physical activity. This study has been designed to investigate the combined influence of intermittent exercise and temperature stress on the modulation of fluoride toxicity. Three-month-old Wistar male rats were exposed to high sodium fluoride (600 ppm) through drinking water for 1 month and the rats were then subjected to swimming exercise at different temperatures (20 degrees C, 25 degrees C, 30 degrees C, and 35 degrees C). Oxidative stress indices analyzed showed fluoride-induced oxidative stress in biological tissues studied like brain, heart, liver, and kidney. Exercise regimen coupled with different temperatures were found to be effective in bringing the oxidative stress indices to near normal level indicating decreased free radical production which may be a compensatory mechanism to counteract against the detrimental effects of fluoride. Further, the deleterious effects of fluoride significantly reduced at 25 degrees C and 30 degrees C demonstrating that the thermoneutral temperatures were effective in reducing the toxicity level. PMID- 22311084 TI - The expression of chicken selenoprotein W, selenocysteine-synthase (SecS), and selenophosphate synthetase-1 (SPS-1) in CHO-K1 cells. AB - Selenoprotein W (SelW) has been found to be ubiquitously expressed in tissues in vivo and was purified more than 18 years ago. However, little in vitro research has been performed on SelW from birds. To detect the mRNA levels of chicken SelW in cultured cell lines, chicken SelW cDNA was cloned into an expression vector. The chicken SelW expression construct was then transfected into CHO-K1 cells. Using RT-PCR and real-time quantitative reverse transcription PCR, we detected the expression of the chicken SelW mRNA. Moreover, the selenocysteine-synthase (SecS) and selenophosphate synthetase-1 (SPS-1) mRNA levels were analyzed. The expression of SelW was detected in SelW-transfected cells; no expression was observed in control cells. Significant increases in the SelW mRNA levels were obtained in chicken SelW-transfected cells relative to control cells. SecS mRNA levels were significantly increased in chicken SelW transfected cells. No significant difference in the SPS-1 level was observed. Our findings show that chicken SelW could be studied in vitro and that SecS and SPS-1 may have potential roles in SelW biosynthesis. PMID- 22311085 TI - Progress toward multiplexed sample-to-result detection in low resource settings using microfluidic immunoassay cards. AB - In many low resource settings multiple diseases are endemic. There is a need for appropriate multi-analyte diagnostics capable of differentiating between diseases that cause similar clinical symptoms. The work presented here was part of a larger effort to develop a microfluidic point-of-care system, the DxBox, for sample-to-result differential diagnosis of infections that present with high rapid-onset fever. Here we describe a platform that detects disease-specific antigens and IgM antibodies. The disposable microfluidic cards are based on a flow-through membrane immunoassay carried out on porous nitrocellulose, which provides rapid diffusion for short assay times and a high surface area for visual detection of colored assay spots. Fluid motion and on-card valves were driven by a pneumatic system and we present designs for using pneumatic control to carry out assay functions. Pneumatic actuation, while having the potential advantage of inexpensive and robust hardware, introduced bubbles that interfered with fluidic control and affected assay results. The cards performed all sample preparation steps including plasma filtration from whole blood, sample and reagent aliquoting for the two parallel assays, sample dilution, and IgG removal for the IgM assays. We demonstrated the system for detection of the malarial pfHRPII antigen (spiked) and IgM antibodies to Salmonella Typhi LPS (patient plasma samples). All reagents were stored on card in dry form; only the sample and buffer were required to run the tests. Here we detail the development of this platform and discuss its strengths and weaknesses. PMID- 22311086 TI - A model of therapist competencies for the empirically supported interpersonal psychotherapy for adolescent depression. AB - In order to treat adolescent depression, a number of empirically supported treatments (ESTs) have been developed from both the cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT-A) frameworks. Research has shown that in order for these treatments to be implemented in routine clinical practice (RCP), effective therapist training must be generated and provided. However, before such training can be developed, a good understanding of the therapist competencies needed to implement these ESTs is required. Sburlati et al. (Clin Child Fam Psychol Rev 14:89-109, 2011) developed a model of therapist competencies for implementing CBT using the well-established Delphi technique. Given that IPT-A differs considerably to CBT, the current study aims to develop a model of therapist competencies for the implementation of IPT-A using a similar procedure as that applied in Sburlati et al. (Clin Child Fam Psychol Rev 14:89 109, 2011). This method involved: (1) identifying and reviewing an empirically supported IPT-A approach, (2) extracting therapist competencies required for the implementation of IPT-A, (3) consulting with a panel of IPT-A experts to generate an overall model of therapist competencies, and (4) validating the overall model with the IPT-A manual author. The resultant model offers an empirically derived set of competencies necessary for effectively treating adolescent depression using IPT-A and has wide implications for the development of therapist training, competence assessment measures, and evidence-based practice guidelines. This model, therefore, provides an empirical framework for the development of dissemination and implementation programs aimed at ensuring that adolescents with depression receive effective care in RCP settings. Key similarities and differences between CBT and IPT-A, and the therapist competencies required for implementing these treatments, are also highlighted throughout this article. PMID- 22311087 TI - Family conflict, emotional security, and child development: translating research findings into a prevention program for community families. AB - The social problem posed by family conflict to the physical and psychological health and well-being of children, parents, and underlying family relationships is a cause for concern. Inter-parental and parent-child conflict are linked with children's behavioral, emotional, social, academic, and health problems, with children's risk particularly elevated in distressed marriages. Supported by the promise of brief psycho-educational programs (e.g., Halford et al. in Journal of Family Psychology 22:497-505, 2008; Sanders in Journal of Family Psychology 22:506-517, 2008), the present paper presents the development and evaluation of a prevention program for community families with children, concerned with family wide conflict and relationships, and building on Emotional Security Theory (Davies and Cummings in Psychological Bulletin 116:387-411, 1994). This program uniquely focuses on translating research and theory in this area into brief, engaging programs for community families to improve conflict and emotional security for the sake of the children. Evaluation is based on multi-domain and multi-method assessments of family-wide and child outcomes in the context of a randomized control design. A series of studies are briefly described in the programmatic development of a prevention program for conflict and emotional security for community families, culminating in a program for family-wide conflict and emotional security for families with adolescents. With regard to this ongoing program, evidence is presented at the post-test for improvements in family-wide functioning, consideration of the relative benefits for different groups within the community, and preliminary support for the theoretical bases for program outcomes. PMID- 22311089 TI - The influence of follistatin on mechanical properties of bone tissue in growing mice with overexpression of follistatin. AB - Mechanical competence of bones is mainly associated with tissue quality that depends on proper bone metabolism processes. An imbalance in the regulation of bone metabolism leads to pathological changes in bone tissue leading to susceptibility to bone fractures and bone deterioration processes. Bone metabolism is regulated to a large extent by the members of the transforming growth factor-beta superfamily, i.e., activins and bone morphogenetic proteins. However, their function is regulated by a single-chain protein called follistatin (FS). The aim of this study was to test the hypothesis that overexpression of FS in growing mice results in impairments in bone morphology and mechanical properties. Moreover, we wanted to investigate how geometrical, structural and material properties of bone tissue change with age. The experiment was performed on growing C57BL/6 TgNK14-mFst/6J mice, overexpressing FS (F mice) versus C57BL/6J mice used as controls (C mice). To establish how overexpression of FS influences bone tissue quality, we studied mice femurs to determine geometrical, structural and material properties of the skeleton. To determine mechanical resistance of bone tissue, femurs were loaded to failure in a three-point bending test. Obtained results indicated that overexpression of FS negatively influences bone metabolism. It was found that mutation results with a significant decrease of all measured biomechanical strength variables in F mice in comparison to C mice. Overexpression of FS leads to decreased quality of skeleton, increasing susceptibility to bone fractures. PMID- 22311090 TI - The relationship between radiological parameters from plain hip radiographs and bone mineral density in a Korean population. AB - The purpose of this study was to investigate the association of the Singh index, cortical thickness index (CTI) and calcar-to-canal (CC) ratio with bone mineral density (BMD) as well as their relationship with physical parameters [age, gender, height, and body mass index (BMI)] in order to assess their potential as an indirect indicator of osteoporosis. BMD, Singh index, CTI and CC ratio as well as the physical parameters were obtained from hip radiographs and clinical records of 140 Korean adults. Linear relationships between the areal BMD of the femoral neck and the parameters as well as between each parameter were obtained. To determine the association between BMD and the radiological parameters, multiple regression analyses were performed after adjusting for the four physical parameters. The CTI was positively associated with BMD (p = 0.040), whereas the Singh index (p = 0.209) and CC ratio (p = 0.655) were not. The CTI was negatively associated with age (p = 0.02) and positively associated with height (p = 0.0001) and BMI (p = 0.001). The CC ratio was also positively associated with age (p = 0.0001) and negatively associated with height (p = 0.033). In conclusion, of three parameters available from plain radiograph (age, height, BMI), only CTI was significantly associated with BMD. CTI can provide a tool for rapid assessment of osteoporosis from plain hip radiographs. PMID- 22311091 TI - Progression from amnesic mild cognitive impairment to Alzheimer's disease: ESR1 and ESR2 polymorphisms and APOE gene. AB - BACKGROUND: Many genes have been studied to determine how they might be involved in Alzheimer's disease (AD). Estrogens have a protective effect in the central nervous system. The mechanisms of action of estrogens are mediated by two estrogen receptors (ERs), ERalpha and ERbeta. Thus, these genes could also play a role in the progression of amnesic mild cognitive impairment (MCIa) to AD. The aim of this study was to examine the role of ER single nucleotide polymorphisms (SNPs) as a risk factor for MCIa, as well as the interaction with apolipoprotein E (APOE) epsilon4 in the progression to AD. METHODS: 79 MCIa patients and 138 healthy controls were analyzed. SNPs were genotyped via restriction fragment length polymorphisms and real-time PCR, RT-PCR or RT-PCR (TaqMan) assays. RESULTS: There is a lack of association between MCIa patients who converted to AD and ER SNPs. APOE epsilon4 allele is an independent risk factor of MCIa (OR=1.86; 95% CI=1.02-3.38, p=0.042) with a high prevalence in converted subjects. APOE epsilon4 is able to predict the progression from MCIa patients to AD (OR=2.55; 95% CI=1.20-5.42, p=0.015). CONCLUSIONS: The presence of the APOE epsilon4 allele, and not the alleles of ER SNPs, is a risk factor for MCIa. Furthermore, APOE genotype seems to predict the conversion from MCIa to AD. PMID- 22311092 TI - Factors affecting survival time after recurrence of non-small-cell lung cancer treated with concurrent chemoradiotherapy. AB - PURPOSE: Dose-fractionation schedules of palliative or salvage radiotherapy (RT) for recurrence of non-small-cell lung cancer (NSCLC) are various because they highly depend on patient prognosis. For optimal selection of dose-fractionation schedules, factors affecting survival time after recurrence were examined. MATERIALS AND METHODS: From 1992 to 2005, 115 patients with stage III NSCLC received curative-intent concurrent chemoradiotherapy (CCRT). Among these patients, 74 underwent recurrence and were reviewed. Evaluated factors were age at recurrence, gender, initial stage, histological subtype, initial radiation field size, recurrent patterns (locoregional alone vs. distant +/- locoregional), time to recurrence (<=6 vs. >6 months), and treatment for recurrence (chemotherapy, RT). RESULTS: Median follow-up time after recurrence was 7 (range 0-59) months. One- and 2-year overall survival rates after recurrence were 28 and 11%, respectively. Based on multivariate analysis, time to recurrence (p = 0.0001) and administration of chemotherapy for recurrence (p = 0.0190) were the independently significant factors. CONCLUSIONS: Early recurrence was the most significant factor for survival after post-CCRT recurrence of NSCLC. Administration of chemotherapy for recurrence was also a significant factor, whereas RT for recurrence was not significant. When RT was given to patients with post-CCRT recurrence of NSCLC, dose-fractionated schedules should be determined considering these factors. PMID- 22311093 TI - Muscle trauma from tourniquet (mis)use. PMID- 22311094 TI - Tracheal flap after percutaneous dilatational tracheotomy. PMID- 22311095 TI - Images in anesthesiology: Spinal subdural hematoma after labor epidural placement. PMID- 22311096 TI - This thy bounty. PMID- 22311097 TI - Estimating duration of infection with avidity assays: potential limitations and recommendations for improvement. AB - Recent infections often have higher pathogen loads. The number of recent infections can therefore be used to estimate transmission rates in a host population. Antibody avidity assays are an emerging technique to infer infection age in both domestic and wild animals. These assays have the potential to supplant intensive mark-recapture efforts for identification of recent infections, but their results may be confounded by antibody titer. We examined the effectiveness of an avidity assay for identifying recent infections of Sin Nombre virus, a hantavirus in North America that establishes a chronic infection in deer mice (Peromyscus maniculatus). We found that assay performance statistics such as sensitivity, specificity, and positive predictive value for low avidity scores were significantly improved when we accounted for antibody titer in the analyses. Without accounting for titer, avidity assays may classify samples with low titers as recent infections regardless of actual infection history, thereby overestimating the number of recent infections in a population and inflating estimates of transmission rates and/or human exposure risk. We recommend that antibody titers meet a minimum threshold for use in avidity assays, and we emphasize the importance of considering titer and dilution in the validation of newly developed avidity assays. PMID- 22311098 TI - The Ecology of fear: host foraging behavior varies with the spatio-temporal abundance of a dominant ectoparasite. AB - Prey engage in myriad behaviors to avoid predation, and these indirect effects of predators on their prey are often measured by the amount of food abandoned by a forager (the "giving-up density", or GUD) in a given habitat. Recent evidence suggests that hosts may engage in comparable behaviors to avoid exposure to parasites. We investigated changes in local foraging and regional space use by mammal hosts for the lone star tick (Amblyomma americanum), using GUDs as an indicator of the perceived risk of parasitism. At eight study sites at the Tyson Research Center (Eureka, MO), we placed two feeding trays, one on the ground and one at 1.5 m height in a tree, in order to assess how the emergence of ground dwelling ticks affected foraging by several mammal species both locally (between the two GUD stations) and regionally (among the eight sites, mean distance 1064 m apart). Though GUDs did not differ between the ground and tree GUD stations, we did find that greater amounts of food were "given-up" at sites with higher abundances of ticks. This increase in food abandonment suggests that hosts respond to the risk of parasitism and alter their space use accordingly, potentially affecting a cascade of other ecological interactions across large spatial scales. PMID- 22311099 TI - Remembering Daumier's blue period. PMID- 22311100 TI - Quantification of diarrhea risk related to wastewater contact in Thailand. AB - Wastewater reuse contributes to closing the nutrient recycling loop as a sustainable way of managing water resources. Bangkok has over a thousand man-made drainage and irrigation canals for such purposes. Its use for agricultural and recreational purposes has a long tradition in rural and peri-urban areas. However, the continuation of these practices is increasingly questioned since potential health risks are an issue if such practices are not appropriately managed. The microbial and chemical quality of canal water has considerably deteriorated over the last decade, mainly because of discharged, untreated domestic and industrial wastewater. It is important to understand the health risks of wastewater reuse and identify risky behaviors from the most highly exposed actors promote the safe use of wastewater. This study assessed diarrhea infection risks caused by the use of and contact with wastewater in Klong Luang municipality, a peri-urban setting in Northern Bangkok, using quantitative microbial risk assessment. Wastewater samples were collected from canals, sewers at household level, and vegetables grown in the canals for consumption. Samples were also collected from irrigation water from the agricultural fields. Two protozoa, Giardia lamblia and Entamoeba histolytica, were quantified and analyzed by real-time PCR, exposure assessment was conducted, and finally, the risk of infection due to contact with wastewater in different scenarios was calculated. The results showed that canal water and vegetables were heavily contaminated with G. lamblia and E. histolytica. Infection risk was high in tested scenarios and largely exceeded the acceptable risk given by WHO guidelines. PMID- 22311101 TI - Synthesis and evaluation of triazole-linked poly(epsilon-caprolactone)-graft poly(2-methyl-2-oxazoline) copolymers as potential drug carriers. AB - Well-defined graft copolymers were obtained using a copper-catalysed azide-alkyne Huisgen's cycloaddition click reaction from both biocompatible and non-toxic poly(epsilon-caprolactone) and poly(2-methyl-2-oxazoline) homopolymers. Resulting amphiphilic copolymers proved to form micelles that could be used as potential drug carriers. PMID- 22311103 TI - Preference for immediate reinforcement over delayed reinforcement: relation between delay discounting and health behavior. AB - Reinforcement from engaging in health behaviors is often delayed by several months or years, a circumstance partly responsible for some people's increased preference for engaging in unhealthy behaviors associated with immediate reinforcement. To examine whether individuals who discount the future engage in fewer health behaviors, 72 young adults completed questionnaires assessing health behaviors and impulsiveness and laboratory-behavioral measures of impulsive decision making. Regression analyses of impulsivity measures predicting health behavior were only significant for one measure, the Experiential Discounting Task, a task in which monetary consequences of choice were actually experienced by study participants. Participants who discounted most by delay (i.e., exhibited impulsive choice) engaged in fewer health behaviors than those who showed less impulsive responding. This task, in contrast to a hypothetical choice task or self-reported impulsiveness, measures the actual behavior of discounting by delay, and was the facet of impulsive decision making most closely associated with adopting a range of health behaviors. PMID- 22311102 TI - A critical appraisal of the hemodynamic signal driving liver regeneration. AB - BACKGROUND: Many aspects of the signaling mechanisms involved in the initiation of hepatic regeneration are under current investigation. Nevertheless, the actual mechanisms switching liver regeneration on and off are still unknown. Hemodynamic changes in the liver following partial hepatectomy have been suggested to be a primary stimulus in triggering liver regeneration. Most of the new knowledge about the impact of hemodynamic changes on liver regeneration is both conceptually important and directly relevant to clinical problems. PURPOSE: The purpose of this review is therefore to exclusively address the hemodynamic signal driving the liver regeneration process. PMID- 22311104 TI - Attachment style and coping in relation to posttraumatic stress disorder symptoms among adults living with HIV/AIDS. AB - Research indicates that a significant proportion of people living with HIV/AIDS report symptoms of posttraumatic stress disorder (PTSD). Moreover, attachment style has been associated with psychological and behavioral outcomes among persons living with HIV/AIDS. Attachment style may influence the ability to cope with traumatic stress and affect PTSD symptoms. To examine the association between attachment style and coping with PTSD symptoms, we assessed 94 HIV positive adults on self-report measures of posttraumatic stress, coping, and attachment style. In multiple regression analysis, avoidant attachment and emotion-focused coping were positively and significantly associated with greater PTSD symptomatology. Support was also found for the moderating effects of avoidant and insecure attachment styles on emotion-focused coping in relation to greater PTSD symptoms. Taken altogether, these results suggest that interventions that develop adaptive coping skills and focus on the underlying construct of attachment may be particularly effective in reducing trauma-related symptoms in adults living with HIV/AIDS. PMID- 22311105 TI - Subependymal seeding of low-grade oligodendroglial neoplasms: a case series. AB - The CSF dissemination of low-grade glial tumors is a known albeit rare entity. Few cases have been reported in the literature. We describe a unique series of six patients with supratentorial low-grade gliomas who presented to our institution at ages 20-41 years, and developed signal abnormality along the margin of the fourth ventricle without enhancement at variable times during their disease course (0 to 95 months). MR spectroscopy and perfusion-weighted imaging through the region of abnormality in two of these patients were consistent with a low-grade glial tumor. We hypothesize that this finding represents dissemination of the supratentorial low-grade glioma along the ventricular ependyma or through the ventricular CSF. Although the small size of our series does not allow us to draw statistically significant conclusions, this abnormality correlates with progression of the supratentorial disease with or without features of a higher grade malignancy. Additional variables that were present in all six patients include the presence of an oligodendroglial component within the supratentorial tumor, mutated IDH1, and the supratentorial tumor contacting the ventricular margin. All six patients were males. PMID- 22311106 TI - Seizure prophylaxis and melanoma brain metastases. AB - Melanoma has a high propensity to metastasize to the brain. In patients with brain metastases (BM) survival is limited, neurologic morbidity is high, with seizure incidence reported up to 67%. Current guidelines recommend against antiepileptic drug prophylaxis (AED PPX) in patients without a history of seizure. We reviewed our experience with melanoma BM to determine the efficacy of AED PPX in the era of second generation AED and to delineate risk factors associated with development of seizures. We reviewed records of all patients treated at Memorial Sloan-Kettering Cancer Center with melanoma and BM between May 2006 and October 2008. Seizure risk was studied relative to BM characteristics at diagnosis and AED PPX. We identified 109 patients. Median age was 61 years (range 29-91); 56% had no neurologic symptoms at diagnosis. On neuroimaging, 94% (102/109) had cortical lesions, 60% (65/109) had more than one supratentorial lesion, 54% (59/109) had hemorrhage. Seizure led to diagnosis of BM in 13% (14/109); 20% (22/109) developed seizures later. On univariate analysis among patients without a seizure at diagnosis, AED-PPX was significantly associated with decreased risk of seizure (P = 0.03) with 3-month seizure rate of 0% compared to 17% without AED-PPX. Hemorrhage (P < 0.001) and multiple supratentorial metastases (P = 0.03) were associated with increased seizure risk. Melanoma patients with multiple supratentorial BM and hemorrhage may have an increased risk of seizure. AED PPX may be effective in selected patients, and should be addressed in a randomized controlled trial. PMID- 22311107 TI - Asymmetric synthesis of alpha,beta-diamino acid derivatives with an aziridine-, azetidine- and gamma-lactone-skeleton via Mannich-type additions across alpha chloro-N-sulfinylimines. AB - The efficient asymmetric synthesis of new chiral gamma-chloro-alpha,beta-diamino acid derivatives via highly diastereoselective Mannich-type reactions of N (diphenylmethylene) glycine esters across a chiral alpha-chloro-N-p toluenesulfinylimine was developed. The influence of the base, LDA or LiHMDS, used for the formation of the glycine enolates, was of great importance for the anti-/syn-diastereoselectivity of the Mannich-type reaction. The gamma-chloro alpha,beta-diamino acid derivatives proved to be excellent building blocks for ring closure towards optically pure anti- and syn-beta,gamma-aziridino-alpha amino esters, and subsequent ring transformation into trans-3-aminoazetidine-2 carboxylic acid derivatives and alpha,beta-diamino-gamma-butyrolactones. PMID- 22311108 TI - Determination of cellulase colocalization on cellulose fiber with quantitative FRET measured by acceptor photobleaching and spectrally unmixing fluorescence microscopy. AB - The determination of cellulase distribution on the surface of cellulose fiber is an important parameter to understand when determining the interaction between cellulase and cellulose and/or the cooperation of different types of cellulases during the enzymatic hydrolysis of cellulose. In this communication, a strategy is presented to quantitatively determine the cellulase colocalization using the fluorescence resonance energy transfer (FRET) methodology, which is based on acceptor photobleaching and spectrally unmixing fluorescence microscopy. FRET monitoring of cellulase colocalization was achieved by labeling cellulases with an appropriate pair of FRET dyes and by adopting an appropriate FRET model. We describe here that the adapted acceptor photobleaching FRET method can be successfully used to quantify cellulase colocalization regarding their binding to a cellulose fiber at a resolution <10 nm. This developed quantitative FRET method is promising for further studying the interactions between cellulase and cellulose and between different types of cellulases. PMID- 22311109 TI - Cardiac and vascular atrogin-1 mRNA expression is not associated with dexamethasone efficacy in the monocrotaline model of pulmonary hypertension. AB - Atrophic signaling elements of the ubiquitin-proteasome system (UPS) are involved in skeletal muscle wasting as well as pressure overload models of heart failure. In our prior experiments, we demonstrated a transcriptional downregulation of atrophy-inducing vascular E3 ubiquitin ligases in a toxic model of pulmonary hypertension where pulmonary artery and right ventricle (RV) hypertrophy are evident. Given the numerous reports of glucocorticoid activation of the UPS and the negative regulator of muscle mass, myostatin, we investigated the efficacy of dexamethasone to reverse monocrotaline (MCT)-induced pulmonary hypertension and augment atrogin-1 expression in both pulmonary arteries and myocardium. Dexamethasone caused significant reductions in body weight in combination with MCT. As predicted, MCT-induced pulmonary hypertension was evident by increases in RV systolic pressure, right ventricle to left ventricle plus septal weight ratios (RV/LVS) and arterial remodeling. MCT treatment significantly reduced both RV and PA atrogin-1 expression. Dexamethasone treatment reversed the MCT-induced pathological indices and restored RV atrogin-1 expression, but did not impact atrogin-1 expression in pulmonary arteries. Myostatin was poorly expressed in pulmonary arteries compared to the RV, and dexamethasone treatment increase RV myostatin in controls but not MCT-treated rats. These findings suggest that mechanisms independent of myostatin/atrogin-1 are responsible for glucocorticoid efficacy in this model of pulmonary hypertension. PMID- 22311110 TI - Behavioral toxicology of cognition: extrapolation from experimental animal models to humans: behavioral toxicology symposium overview. AB - A variety of behavioral instruments are available for assessing important aspects of cognition in both animals and humans and, in many cases, the same instruments can be used in both. While nonhuman primates are phylogenetically closest to humans, rodents, pigeons and other animals also offer behaviors worthy of note. Delay Discounting procedures are as useful as any in studies of impulsivity and may have utility in shedding light on processes associated with drug abuse. Specific memory tests such as Visual Paired Comparisons tasks (similar to the Fagan test of infant intelligence) can be modified to allow for assessment of different aspects of memory such as spatial memory. Use of these and other specific memory tasks can be used to directly monitor aspects of cognitive development in infant animals, particularly in nonhuman primates such as monkeys, and children and to draw inferences with respect to possible neuroanatomical substrates sub-serving their functions. Tasks for assessing working memory such as Variable Delayed Response (VDR), modified VDR and Spatial Working Memory tasks are now known to be affected in Parkinson's disease (PD). These and other cognitive function tasks are being used in a monkey model of PD to assess the ability of anti-Parkinson's disease therapies to ameliorate these cognitive deficits without diminishing their therapeutic effects on motor dysfunction. Similarly, in a rat model of the cognitive deficits associated with perinatal exposure to polychlorinated biphenyls (PCBs), clear parallels with children can be seen in at least two areas of executive function: cognitive flexibility and response inhibition. In the rat model, discrimination reversal tasks were utilized to assess cognitive flexibility, a function often assessed in humans using the Wisconsin Card Sorting Task. Response inhibition was assessed using performance in a Differential Reinforcement of Low Response Rates (DRL) task. As the data continue to accumulate, it becomes more clear that our attempts to adapt animal-appropriate tasks for the study of important aspects of human cognition have proven to be very fruitful. PMID- 22311112 TI - Trends in soil erosion and woody shrub encroachment in Ngqushwa district, Eastern Cape Province, South Africa. AB - Woody shrub encroachment severely impacts on the hydrological and erosion response of rangelands and abandoned cultivated lands. These processes have been widely investigated at various spatial scales, using mostly field experimentation. The present study used remote sensing to investigate spatial and temporal patterns of soil erosion and encroachment by a woody shrub species, Pteronia incana, in a catchment in Ngqushwa district, Eastern Cape Province, South Africa between 1998 and 2008. The extreme categories of soil erosion and shrub encroachment were mapped with higher accuracy than the intermediate ones, particularly where lower spatial resolution data were used. The results showed that soil erosion in the worst category increased simultaneously with dense woody shrub encroachment on the hill slopes. This trend is related to the spatial patterning of woody shrub vegetation that increases bare soil patches--leading to runoff connectivity and concentration of overland flow. The major changes in soil erosion and shrub encroachment analysed during the 10-year period took place in the 5-9 degrees slope category and on the concave slope form. Multi-temporal analyses, based on remote sensing, can extend our understanding of the dynamics of soil erosion and woody shrub encroachment. They may help benchmark the processes and assist in upscaling field studies. PMID- 22311111 TI - Extraskeletal benefits and risks of calcium, vitamin D and anti-osteoporosis medications. AB - Drugs used for the prevention and the treatment of osteoporosis exert various favourable and unfavourable extra-skeletal effects whose importance is increasingly recognized notably for treatment selection. INTRODUCTION: The therapeutic armamentarium for the prevention and the treatment of osteoporosis is increasingly large, and possible extra-skeletal effects of available drugs could influence the choice of a particular compound. METHODS: The present document is the result of a national consensus, based on a systematic and critical review of the literature. RESULTS: Observational research has suggested an inverse relationship between calcium intake and cardiovascular diseases, notably through an effect on blood pressure, but recent data suggest a possible deleterious effect of calcium supplements on cardiovascular risk. Many diverse studies have implicated vitamin D in the pathogenesis of clinically important non-skeletal functions or diseases, especially muscle function, cardiovascular disease, autoimmune diseases and common cancers. The possible effects of oral or intravenous bisphosphonates are well-known. They have been associated with an increased risk of oesophageal cancer or atrial fibrillation, but large-scale studies have not found any association with bisphosphonate use. Selective oestrogen receptor modulators have demonstrated favourable or unfavourable extra skeletal effects that vary between compounds. Strontium ranelate has a limited number of non-skeletal effects. A reported increase in the risk of venous thromboembolism is not found in observational studies, and very rare cases of cutaneous hypersensitivity reactions have been reported. Denosumab has been introduced recently, and its extra-skeletal effects still have to be assessed. CONCLUSION: Several non-skeletal effects of bone drugs are well demonstrated and influence treatment choices. PMID- 22311113 TI - Potent inhibition of dinuclear zinc(II) peptidase, an aminopeptidase from Aeromonas proteolytica, by 8-quinolinol derivatives: inhibitor design based on Zn2+ fluorophores, kinetic, and X-ray crystallographic study. AB - The selective inhibition of an aminopeptidase from Aeromonas proteolytica (AAP), a dinuclear Zn(2+) hydrolase, by 8-quinolinol (8-hydroxyquinoline, 8-HQ) derivatives is reported. We previously reported on the preparation of 8-HQ pendant cyclens as Zn(2+) fluorophores (cyclen is 1,4,7,10 tetraazacyclododecane), in which the nitrogen and phenolate of the 8-HQ units (as well as the four nitrogens of cyclen) bind to Zn(2+) in a bidentate manner to form very stable Zn(2+) complexes at neutral pH (K (d) = 8-50 fM at pH 7.4). On the basis of this finding, it was hypothesized that 8-HQ derivatives have the potential to function as specific inhibitors of Zn(2+) enzymes, especially dinuclear Zn(2+) hydrolases. Assays of 8-HQ derivatives as inhibitors were performed against commercially available dinuclear Zn(2+) enzymes such as AAP and alkaline phosphatase. 8-HQ and the 5-substituted 8-HQ derivatives were found to be competitive inhibitors of AAP with inhibition constants of 0.16-29 MUM at pH 8.0. The nitrogen at the 1-position and the hydroxide at the 8-position of 8-HQ were found to be essential for the inhibition of AAP. Fluorescence titrations of these drugs with AAP and an X-ray crystal structure analysis of an AAP-8-HQ complex (1.3-A resolution) confirmed that 8-HQ binds to AAP in the "Pyr-out" mode, in which the hydroxide anion of 8-HQ bridges two Zn(2+) ions (Zn1 and Zn2) in the active site of AAP and the nitrogen atom of 8-HQ coordinates to Zn1 (Protein Data Bank code 3VH9). PMID- 22311114 TI - Effects of chirality on the intracellular localization of binuclear ruthenium(II) polypyridyl complexes. AB - Interest in binuclear ruthenium(II) polypyridyl complexes as luminescent cellular imaging agents and for biomedical applications is increasing rapidly. We have investigated the cellular localization, uptake, and biomolecular interactions of the pure enantiomers of two structural isomers of [MU-bipb(phen)(4)Ru(2)](4+) (bipb is bis(imidazo[4,5-f]-1,10-phenanthrolin-2-yl)benzene and phen is 1,10 phenanthroline) using confocal laser scanning microscopy, emission spectroscopy, and linear dichroism. Both complexes display distinct enantiomeric differences in the staining pattern of fixed cells, which are concluded to arise from chiral discrimination in the binding to intracellular components. Uptake of complexes in live cells is efficient and nontoxic at 5 MUM, and occurs through an energy dependent mechanism. No differences in uptake are observed between the structural isomers or the enantiomers, suggesting that the interactions triggering uptake are rather insensitive to structural variations. Altogether, these findings show that the complexes investigated are promising for future applications as cellular imaging probes. In addition, linear dichroism shows that the complexes exhibit DNA-condensing properties, making them interesting as potential gene delivery vectors. PMID- 22311115 TI - Quantitative magnetic resonance angiography. PMID- 22311116 TI - Anticoagulation in neurointerventions: basic pharmacology and pathophysiology, current status, practical advice. AB - This article gives an overview of anticoagulative medication accompanying neurointerventional procedures. The basic pharmacology of prevalent medication is outlined and the thrombogenicity of standard procedures is described. A brief overview of the literature on risks and benefits of standard medications and their monitoring is provided. A customized regime of care is presented. PMID- 22311117 TI - Amine-catalyzed formal (3 + 3) annulations of 2-(acetoxymethyl)buta-2,3-dienoate with sulfur ylides: synthesis of 4H-pyrans bearing a vinyl sulfide group. AB - A DABCO-catalyzed (3 + 3) annulation between 2-(acetoxymethyl)buta-2,3-dienoate and sulfur ylides has been developed, which provides a facile method for the synthesis of 4H-pyrans bearing a vinyl sulfide group. PMID- 22311118 TI - Cell cycle proteins predict recurrence in stage II and III colon cancer. AB - PURPOSE: To investigate the prognostic value of multiple cell cycle-associated proteins in a large series of stage II and III colon cancers. METHODS: From formalin-fixed, paraffin-embedded tumor samples of 386 patients with stage II and III colon cancer, DNA was isolated and tissue microarrays were constructed. Tissue microarray slides were immunohistochemically stained for p21, p27, p53, epidermal growth factor receptor, Her2/Neu, beta-catenin, cyclin D1, Ki-67, thymidylate synthase, and Aurora kinase A (AURKA). Polymerase chain reaction based microsatellite instability analysis was performed to allow for stratification of protein expression by microsatellite instability status. RESULTS: Overall, low p21, high p53, low cyclin D1, and high AURKA expression were significantly associated with recurrence (P = 0.01, P < 0.01, P = 0.04, and P < 0.01, respectively). In stage II patients who did not receive adjuvant chemotherapy (n = 190), significantly more recurrences were observed in case of low-p21 and high-p53-expressing tumors (P < 0.01 and P = 0.03, respectively). In stage III patients who did not receive chemotherapy, high p53 expression was associated with recurrence (P = 0.02), and in patients who received chemotherapy, high AURKA expression was associated with relapse (P < 0.01). In patients with microsatellite stable tumors, high levels of p53 and AURKA were associated with recurrence (P = 0.01 and P < 0.01, respectively). Multivariate analysis showed p21 (odds ratio 1.6, 95% confidence interval 0.9-2.8) and AURKA (odds ratio 2.7, 95% confidence interval 1.3-5.6) to be independently associated with disease recurrence. CONCLUSIONS: p21, p53, cyclin D1, and AURKA could possibly be used as prognostic markers to identify colon cancer patients with high risk of disease recurrence. PMID- 22311119 TI - MicroRNA-200b regulates cell proliferation, invasion, and migration by directly targeting ZEB2 in gastric carcinoma. AB - BACKGROUND: The microRNA-200 (miR-200) family has been reported to induce epithelial differentiation and suppress epithelial-mesenchymal transition (EMT) by inhibiting translation of zinc finger E-box-binding homeobox (ZEB) 1 and 2 mRNAs in several types of cancers. This study aimed to clarify the role of miR 200b in regulating EMT and promoting cellular proliferation, invasion, and migration in gastric cancer. METHODS: The relationships among the expression levels of miR-200b, ZEB1 and ZEB2, and E-cadherin mRNAs were analyzed by quantitative real-time reverse transcription-polymerase chain reaction in frozen tissue samples from 40 gastric cancer patients who underwent gastrectomy from 2008 to 2010. The effects of miR-200b on EMT in gastric cancer cells in vitro were also analyzed. RESULTS: Diffuse histologic type, depth of tumor, tumor size, lymph node metastasis, and lymphatic invasion were significantly higher in the low-miR-200b expression group compared with the high expression group. There was a strong correlation between the levels of miR-200b, and ZEB2 and E-cadherin mRNAs in gastric cancer patients. Upregulation of miR-200b in gastric cancer cells changed the cell morphology from fibroblast- to epithelial-like, associated with localization of E-cadherin to the plasma membrane. ZEB2 mRNA levels fell, while E-cadherin expression levels increased in gastric cells overexpressing miR 200b, associated with significantly reduced cellular proliferation, and inhibition of cellular migration and invasion. CONCLUSIONS: miR-200b regulates ZEB2 expression and thus controls metastasis in gastric cancer. PMID- 22311120 TI - Severe duodenal involvement in familial adenomatous polyposis treated by pylorus preserving pancreaticoduodenectomy. AB - PURPOSE: Pancreaticoduodenectomy is an alternative to pancreas-sparing duodenectomy for radical treatment of duodenal lesions. The aims of this study were to assess the results of pylorus-preserving pancreaticoduodenectomy (PPPD) for severe duodenal polyposis in familial adenomatous polyposis in terms of morbidity, long-term influence on functional results, the recurrence rate of cancer or jejunal polyps, and survival. METHODS: All patients operated on for a PPPD between 1992 and 2009 were included. Clinical data, endoscopic findings, and pathologic examinations were evaluated. RESULTS: A total of 19 patients underwent PPPD for severe duodenal polyposis (17 Spigelman IV, 1 Spigelman III, and 1 invasive carcinoma). Postoperative mortality was nil. The postoperative morbidity rate was 42%, including 4 pancreatic fistulae (21%) and 2 delayed gastric emptying (11%). Pathologic examination found 7 invasive carcinomas, of which only 1 was known before resection. One third of patients operated on without a preoperative diagnosis of malignancy already had an invasive duodenal carcinoma. After a mean follow-up of 58 months, 16 patients were alive. Thirteen patients underwent endoscopic follow-up, and new adenomas were found in 4 (31%). All were treated successfully during the same endoscopic procedure. PPPD did not modify the functional result after coloproctectomy. CONCLUSIONS: PPPD remains a safe and efficient therapeutic option for severe duodenal polyposis in familial adenomatous polyposis patients. PMID- 22311121 TI - Mechanical disruption of mammalian cells in a microfluidic system and its numerical analysis based on computational fluid dynamics. AB - The lysis of mammalian cells is an essential part of different lab-on-a-chip sample preparation methods, which aim at the release, separation, and subsequent analysis of DNA, proteins, or metabolites. Particularly for the analysis of compartmented in vivo metabolism of mammalian cells, such a method must be very fast compared to the metabolic turnover-rates, it should not affect the native metabolite concentrations, and should ideally leave cell organelles undamaged. So far, no such a method is available. We have developed a microfluidic system for the effective rapid mechanical cell disruption and established a mathematical model to describe the efficiency of the system. Chinese hamster ovary (CHO) cells were disrupted with high efficiency by passing through two consecutive micronozzle arrays. Simultaneous cell compression and shearing led to a disruption rate of >=90% at a sample flow rate of Q = 120 MUL min(-1) per nozzle passage, which corresponds to a mean fluid velocity of 13.3 m s(-1) and a mean Reynolds number of 22.6 in the nozzle gap. We discussed the problem of channel clogging by cellular debris and the resulting flow instability at the micronozzle arrays. The experimental results were compared to predictions from Computational Fluid Dynamics (CFD) simulations and the critical energy dissipation rate for the disruption of the CHO cell population with known size distribution was determined to be 4.7 * 10(8) W m(-3). Our model for the calculation of cell disruption on the basis of CFD-data could be applied to other microgeometries to predict intended disruption or undesired cell damage. PMID- 22311123 TI - Charities plead with government not to delay law on foreign aid commitment. PMID- 22311122 TI - Pannexin 1 forms an anion-selective channel. AB - Pannexin 1 (Panx1) is expressed in various mammalian tissues including the brain and immune cells. Here, we present evidence that Panx1 when expressed in mammalian cells, forms anion-selective channels, with a rank order of permeabilities: NO (3) (-)> I(-) > Br (-)> Cl (-) > F (-)>> aspartate (-)~ glutamate (-)~ gluconate(-). Single-channel Panx1-mediated currents have a unitary conductance around 68 pS. Our results show that Panx1 assembles into a membrane anion channel with a relatively low single-channel conductance. PMID- 22311124 TI - Nearly 2000 amendments are not enough to save health bill, says BMA. PMID- 22311125 TI - Health services research evaluation principles. Broadening a general framework for evaluating health information technology. AB - BACKGROUND: Our forthcoming national experiment in increased health information technology (HIT) adoption funded by the American Recovery and Reinvestment Act of 2009 will require a comprehensive approach to evaluating HIT. The quality of evaluation studies of HIT to date reveals a need for broader evaluation frameworks that limits the generalizability of findings and the depth of lessons learned. OBJECTIVE: Develop an informatics evaluation framework for health information technology (HIT) integrating components of health services research (HSR) evaluation and informatics evaluation to address identified shortcomings in available HIT evaluation frameworks. METHOD: A systematic literature review updated and expanded the exhaustive review by Ammenwerth and deKeizer (AdK). From retained studies, criteria were elicited and organized into classes within a framework. The resulting Health Information Technology Research-based Evaluation Framework (HITREF) was used to guide clinician satisfaction survey construction, multi-dimensional analysis of data, and interpretation of findings in an evaluation of a vanguard community health care EHR. RESULTS: The updated review identified 128 electronic health record (EHR) evaluation studies and seven evaluation criteria not in AdK: EHR Selection/Development/Training; Patient Privacy Concerns; Unintended Consequences/ Benefits; Functionality; Patient Satisfaction with EHR; Barriers/Facilitators to Adoption; and Patient Satisfaction with Care. HITREF was used productively and was a complete evaluation framework which included all themes that emerged. CONCLUSIONS: We can recommend to future EHR evaluators that they consider adding a complete, research based HIT evaluation framework, such as HITREF, to their evaluation tools suite to monitor HIT challenges as the federal government strives to increase HIT adoption. PMID- 22311126 TI - Remembering and listening. PMID- 22311127 TI - Hispanic Infants with cystic fibrosis show low CFTR mutation detection rates in the Illinois newborn screening program. AB - States develop specific protocols for cystic fibrosis (CF) newborn screening to reflect the population served. We hypothesized that mutation distribution and detection rates would differ between Hispanic and non-Hispanic CF patients diagnosed by IL newborn screen with more Hispanic infants carrying mutations not detected by the state panel. Data from CF cases diagnosed via newborn screen in IL between 3/1/2008 and 10/31/2010 were reviewed. More Hispanic infants with CF had one or more undefined mutations after screening, in comparison to non Hispanic Caucasian patients (40% vs. 9.5%; p < 0.002). The risk of having a positive diagnosis of CF with only one mutation noted by positive newborn screen increases 2-fold in Hispanic Caucasian versus non-Hispanic Caucasian infants (5% vs. 2.4%). Health care providers must be aware of the limitations of CF newborn screening to ensure appropriate counseling and prompt referral for a positive newborn screen, even when zero or one mutations are identified. PMID- 22311128 TI - Neuroinflammation and synaptic loss. AB - Neuroinflammation plays a critical role in the progression of many neurodegenerative, neuropsychiatric and viral diseases. In neuroinflammation, activated microglia and astrocytes release cytokines and chemokines as well as nitric oxide, which in turn activate many signal transduction pathways. The cytokines, interleukin-1 beta and tumor necrosis factor alpha, regulate transcription of a number of genes within the brain, which can lead to the formation of pro-inflammatory products of the arachidonic acid cascade. Formation of pro-inflammatory agents and associated cytotoxic products during neuroinflammation can be detrimental to neurons by altering synaptic proteins. Neuroinflammation as well as excitotoxic insults reduce synaptic markers such as synaptophysin and drebrin. Neurodegenerative, neuropsychiatric illnesses and viral infections are accompanied by loss of both pre- and post-synaptic proteins. These synaptic changes may contribute to the progressive cognitive decline and behavioral changes associated with these illnesses. PMID- 22311129 TI - The CB1 receptor-mediated endocannabinoid signaling and NGF: the novel targets of curcumin. AB - Increasing interest has recently been attracted towards the identification of natural compounds including those with antidepressant properties. Curcumin has shown promising antidepressant effect, however, its molecular target(s) have not been well defined. Based on the interaction between the neurotrophins and endocannabinoid system as well as their contribution to the emotional reactivity and antidepressant action, here we show that 4-week treatment with curcumin, similar to the classical antidepressant amitriptyline, results in the sustained elevation of brain nerve growth factor (NGF) and endocannabinoids in dose dependent and brain region-specific fashion. Pretreatment with cannabinoid CB(1) receptor neutral antagonist AM4113, but not the CB(2) antagonist SR144528, prevents the enhancement of brain NGF contents. AM4113 exerts no effect by itself. Our findings by presenting the CB(1) receptor-mediated endocannabinoid signaling and NGF as novel targets for curcumin, suggest that more attention should be focused on the therapeutic potential of herbal medicines including curcumin. PMID- 22311130 TI - Overcoming obstacles to resident-patient continuity of care. AB - OBJECTIVE: Because continuity of care (CC) is a necessary component of resident education, this analysis was done to understand what keeps CC between residents and patients low and how it can be most effectively improved. BACKGROUND: Many authors lament low CC between residents and patients, especially in the era of duty hour regulations. Some have tried lengthening rotations, some have tried increasing clinic attendance, and some have argued for various training models. Little detailed analysis has been done to identify root causes of low CC or ways to improve it. METHODS: Two months of charts were reviewed to estimate baseline CC on a vascular surgery rotation. Probability theory and engineering simulations were used to determine whether CC can be enhanced by (a) lengthening rotations, (b) altering observed logistical patterns, (c) using a "resident return" model where residents are able to see patients postoperatively even if moved to a different rotation, or (d) employing an apprenticeship model. RESULTS: Baseline analysis showed residents had 0% CC given 131 opportunities to do so. Probability analysis and the simulation outcomes suggest that rotation length plays a minor role in achieving CC. Logistical changes showed some improvement in CC, but not as much as using an apprenticeship rotation model. CONCLUSIONS: The limitations placed on CC by rotation duration are real, but lengthening the rotation does not meaningfully resolve the gap between acceptable CC levels and actual levels. Although CC can be enhanced with longer rotations if coupled with the use of the resident return model, the greater barrier to CC is the logistical patterns such as where residents spend time, how cases are assigned, and the lack of an alert system to inform residents about returning postoperative patients. The apprenticeship model enables residents to achieve CC closer to that of the faculty. PMID- 22311131 TI - "Inherent limitations" in donors: control matched study of consequences following a right hepatectomy for living donation and benign liver lesions. AB - OBJECTIVE: The aim of this study was to identify "inherent limitations" in healthy donors who are responsible for donor morbidity after right hepatectomy (RH) for adult-to-adult living donor liver transplantation (ALDLT). BACKGROUND: Right hepatectomy for ALDLT remains a challenging procedure without significant improvement in morbidity over time. This suggests some "inherent limitations" in healthy individuals, which are beyond the recent improvements in the donor evaluation and selection process and refinements in surgical technique during the learning curve. METHODS: To identify response of RH in ALDLT, we prospectively studied 32 patients requiring an RH for benign liver lesions (BL), matched with 32 living donors (LD) operated by same team. All patients underwent liver volume evaluation by computed tomographic (CT) volumetry preoperatively and 1 week after RH, postoperative complications graded with Clavien's system. RESULTS: The comparison (LD vs BL) showed that remnant liver volume (RLV) on preoperative CT volumetry was higher in the BL group (450 +/- 150 vs 646 +/- 200 mL, P < 0.001) representing 31% +/- 7% in LD group versus 36% +/- 7% of the total liver volume in BL group (P = 0.03). On postoperative day 7, the RLV was similar in the 2 groups (866 +/- 162 vs 941 +/- 153 mL) resulting from a significantly higher regeneration rate in the LD group (89% vs 55%, P = 0.009). Overall complications rate was lower in the BL group (46% vs 21%, P = 0.035). CONCLUSIONS: Right hepatectomy in LDLT induces a more severe deprivation of liver volume than in BL, which induce an accelerated regeneration. Accelerated regeneration could represent "inherent limitation" in healthy donors that makes them more vulnerable for postoperative complications. PMID- 22311133 TI - Mutagenesis and biochemical studies on AuaA confirmed the importance of the two conserved aspartate-rich motifs and suggested difference in the amino acids for substrate binding in membrane-bound prenyltransferases. AB - AuaA is a membrane-bound farnesyltransferase from the myxobacterium Stigmatella aurantiaca involved in the biosynthesis of aurachins. Like other known membrane bound aromatic prenyltransferases, AuaA contains two conserved aspartate-rich motifs. Several amino acids in the first motif NXxxDxxxD were proposed to be responsible for prenyl diphosphate binding via metal ions like Mg(2+). Site directed mutagenesis experiments demonstrated in this study that asparagine, but not the arginine residue in NRxxDxxxD, is important for the enzyme activity of AuaA, differing from the importance of NQ or ND residues in the NQxxDxxxD or NDxxDxxxD motifs observed in some membrane-bound prenyltransferases. The second motif of known membrane-bound prenyltransferases was proposed to be involved in the binding of their aromatic substrates. KDIxDxEGD, also found in AuaA, had been previously speculated to be characteristic for binding of flavonoids or homogenisate. Site-directed mutagenesis experiments with AuaA showed that KDIxDxEGD was critical for the enzyme activity. However, this motif is very likely not specific for flavonoid or homogenisate prenyltransferases, because none of the tested flavonoids was accepted by AuaA or its mutant R53A in the presence of farnesyl, geranyl or dimethylallyl diphosphate. PMID- 22311134 TI - Coupling between GABA(A)-R ligand-binding activity and membrane organization in beta-cyclodextrin-treated synaptosomal membranes from bovine brain cortex: new insights from EPR experiments. AB - Correlations between GABA(A) receptor (GABA(A)-R) activity and molecular organization of synaptosomal membranes (SM) were studied along the protocol for cholesterol (Cho) extraction with beta-cyclodextrin (beta-CD). The mere pre incubation (PI) at 37 degrees C accompanying the beta-CD treatment was an underlying source of perturbations increasing [(3)H]-FNZ maximal binding (70%) and K (d) (38%), plus a stiffening of SMs' hydrocarbon core region. The latter was inferred from an increased compressibility modulus (K) of SM-derived Langmuir films, a blue-shifted DPH fluorescence emission spectrum and the hysteresis in DPH fluorescence anisotropy (A (DPH)) in SMs submitted to a heating-cooling cycle (4-37-4 degrees C) with A (DPH,heating) < A (DPH,cooling). Compared with PI samples, the beta-CD treatment reduced B (max) by 5% which correlated with a 45% decrement in the relative Cho content of SM, a decrease in K and in the order parameter in the EPR spectrum of a lipid spin probe labeled at C5 (5-SASL), and significantly increased A (TMA-DPH). PI, but not beta-CD treatment, could affect the binding affinity. EPR spectra of 5-SASL complexes with beta-CD-, SM partitioned, and free in solution showed that, contrary to what is usually assumed, beta-CD is not completely eliminated from the system through centrifugation washings. It was concluded that beta-CD treatment involves effects of at least three different types of events affecting membrane organization: (a) effect of PI on membrane annealing, (b) effect of residual beta-CD on SM organization, and (c) Cho depletion. Consequently, molecular stiffness increases within the membrane core and decreases near the polar head groups, leading to a net increase in GABA(A)-R density, relative to untreated samples. PMID- 22311135 TI - Origin of the cannula for tracheotomy during the middle ages and Renaissance. AB - The purpose of this article was to trace the historical origin of the inserted cannula during tracheotomy. Tracheotomy is mentioned in most ancient medical texts, but the origin of cannula insertion into the windpipe is unclear. We reviewed the incunabula and Renaissance texts reporting the utilization of surgical cannulas and tracheotomy. The incunabula disclosed extended use of surgical cannulas during the middle ages and Renaissance. Although tracheotomy was advocated in acutely suffocating patients for a disease of the throat termed squinantia or angina, the first report of the procedure was found only at the end of the middle ages and a second during the middle Renaissance. The introduction of cannula use in tracheotomy was supported by a semantic misinterpretation by Antonio Musa Brasavola. The historical origin for tracheotomy in the middle ages and Renaissance is conflicting. Antonio Brasavola wrongly interpreted Avicenna's oral cannula introduced into the windpipe for angina. This misinterpretation allowed Giulio Casserio to draw the first curved cannula introduced for used during tracheotomy. PMID- 22311136 TI - Prognostic factors and treatment outcomes for anaplastic thyroid carcinoma: ATC Research Consortium of Japan cohort study of 677 patients. AB - BACKGROUND: Anaplastic thyroid carcinoma (ATC) accounts for only 1 to 2% of all thyroid carcinomas, but it is one of the most lethal neoplasms in humans. To date, most findings about ATC have been derived from single-institution studies with limited numbers of cohorts. To obtain further insights into this "orphan disease," we have established a multicenter registry, the ATC Research Consortium of Japan (ATCCJ). We analyzed prognostic factors and treatment outcomes using the large cohort database of the ATCCJ. METHODS: Most of the Japanese centers involved in the treatment of thyroid cancer were invited to join the ATCCJ and have provided information on ATC patients treated between 1995 and 2008. The database includes 677 cases from 38 registered institutions. Survival curves were determined using Kaplan-Meier methods and were compared using the log-rank test. Cox's proportional hazards model was used for multivariate analysis. RESULTS: Clinical varieties of ATC were classified into four types: common type (n = 547); incidental type (n = 29); anaplastic transformation at the neck (n = 95); anaplastic transformation at a distant site (n = 6). The incidental type followed by anaplastic transformation at the neck showed better outcomes than the other types. Anaplastic transformation at a distant site showed the worst outcomes. The 6-month and 1-year cause-specific survival (CSS) rates for common-type ATC were 36 and 18%, respectively. In all, 84 (15%) achieved long-term (>1 year) survival. Multivariate analysis identified age >=70 years, presence of acute symptoms, leukocytosis (white blood cell count >=10,000/mm(3)), large tumor >5 cm, T4b tumor, and distant metastasis as significant risk factors for lower survival. CSS rates also differed significantly depending on UICC stages, with 6-month CSSs of 60% for stage IVA, 45% for IVB, and 19% for IVC. For 36 of 69 (52%) stage IVA patients who underwent radical surgery, adjuvant therapies, including radiation therapy (RTX) and chemotherapy (CTX) did not show additional benefit statistically. Conversely, among 242 stage IVB patients, 80 (33%) underwent radical surgery. For those patients, therapies combining RTX with CTX significantly improved CSS. CONCLUSIONS: Long-term survival is possible for selected patients with ATC. To determine the treatment strategy, UICC stage (disease extent) and other prognostic factors (e.g., biologic malignancy grade) should be considered. PMID- 22311137 TI - New invagination procedure for pancreaticojejunostomy using only four sutures. AB - BACKGROUND: Pancreaticoenterostomy remains one of the most stressful parts of pancreatoduodenectomy. We introduce herein a new convenient and secure invagination procedure for pancreaticojejunostomy. METHODS: We performed our new procedure during pancreatoduodenectomy in 15 consecutive patients (7 men, 8 women). The features of the procedure are as follows. First, it is performed using only four sutures. Second, the pancreas stump is invaginated into the jejunum, mainly by two sutures that penetrate the parenchyma and are continuously purse-string sutured to the jejunum. Third, all needle holes on the surface of the pancreas are covered with the jejunal wall. RESULTS: Eight patients were classified as showing no pancreatic fistula, and seven displayed a grade A fistula, according to the International Study Group on Pancreatic Fistula criteria. The median operating time for these 15 patients using the present procedure was about 60 min shorter than that for the previous nine patients who underwent duct-to-mucosa pancreaticogastrostomy in our hospital. CONCLUSIONS: The present method allows pancreaticojejunostomy to be performed swiftly and conveniently. PMID- 22311138 TI - Laparoscopic appendectomy in pregnant women: experience in Chittagong, Bangladesh. AB - BACKGROUND: Surgery may be needed during pregnancy for nonobstetric reasons, most commonly appendicitis, and laparoscopy is considered as safe as the open method, for both mother and fetus. The aim of the present study was to emphasize the feasibility of laparoscopic appendectomy during pregnancy in a developing country, and also to report the first study of its kind from Bangladesh. MATERIALS AND METHODS: From 7 October 2005 to 6 October 2010, 31 pregnant women were diagnosed with acute appendicitis. Diagnoses were based on clinical suspicion supported by ultrasonogram. Under general endotracheal anesthesia, laparoscopy was done in all 31 cases. One gynecologist was always present to monitor the conditions of the fetus preoperatively and postoperatively. Feeding was allowed 6 h after surgery, and the majority of the patients were discharged on the second postoperative day. Age, gestational period, operative time, hospital stay, maternal and fetal outcome, and complications were evaluated. RESULTS: Age ranged from 19 to 35 years and gestational period ranged from 6 to 31 weeks. Right lower quadrant pain was the presenting complaint in majority of cases. Average operative time was 34 +/- 10.19 min, and there were no conversions to open surgery. There were no intraoperative or immediate postoperative hazards. Postoperative recovery was uneventful in all cases. Histopathology of 30 cases confirmed appendicitis. One patient, whose fetus was at 12 weeks gestation at the time of the appendectomy had a spontaneous abortion 1 month later. There were no adverse outcomes during the follow-up period. CONCLUSIONS: Laparoscopy is a safe and effective technique for the treatment of appendicitis during pregnancy and can be performed in a developing country. PMID- 22311139 TI - Pilot testing of a population-based surgical survey tool in Sierra Leone. AB - BACKGROUND: The prevalence of surgical diseases in low income countries is thought to be very large, but to date no population-based survey has documented the need. The Surgeons OverSeas Assessment of Surgical Need (SOSAS) is a survey tool programmed for use with iPads to measure the prevalence of surgical conditions. METHODS: To assess the appropriateness and utility of SOSAS, a pilot test was undertaken in Sierra Leone. Local medical students were trained in sampling, interviewing, and SOSAS specifics. Five clusters of 10 households were randomly selected and 100 individuals were interviewed. Problems with the tool, iPad use, and respondent answers were collected. Daily debriefings with the enumerators aimed to identify problems and ways for improvement. RESULTS: Administering SOSAS via iPads was found to be easy and facilitated data entry. Quick analysis of the data allowed for rapid feedback. Although the survey has 450 possible data entry points, by using conditional formatting, the enumerators were able to collect household demographics and interview two randomly selected household members in an average of 25 min. The survey methodology was acceptable, with a response rate of 96%. Five major sections were amended after the pilot. DISCUSSION: Pilot testing of SOSAS showed that a population-based survey measuring the prevalence of surgical disease could be undertaken in a low income country. It is recommended that SOSAS be used with a larger sample size to calculate the prevalence of surgical disease in low income countries. PMID- 22311140 TI - Hepatocellular telomere length in biliary atresia measured by Q-FISH. AB - BACKGROUND: Liver transplantation for biliary atresia is indicated whenever a Kasai portoenterostomy is considered unfeasible. However, the timing of liver transplantation in biliary atresia has not been precisely defined. Excessive shortening of hepatocellular telomeres may occur in patients with biliary atresia, and therefore, telomere length could be a predictor of hepatocellular reserve capacity. METHODS: Hepatic tissues were obtained from 20 patients with biliary atresia who underwent LT and 10 age-matched autopsied individuals (mean age, 1.7 and 1.2 years, respectively). Telomere lengths were measured by Southern blotting and quantitative fluorescence in situ hybridization using the normalized telomere-centromere ratio. The correlation between the normalized telomere centromere ratio for the hepatocytes in biliary atresia and the pediatric end stage liver disease score was analyzed. RESULTS: The median terminal restriction fragment length of the hepatic tissues in biliary atresia was not significantly different from that of the control (p = 0.425), whereas the median normalized telomere-centromere ratio of hepatocytes in biliary atresia was significantly smaller than that of the control (p < 0.001). Regression analysis demonstrated a negative correlation of the normalized telomere-centromere ratio with the pediatric end-stage liver disease score in biliary atresia (p < 0.001). CONCLUSIONS: Telomere length analysis using quantitative fluorescence in situ hybridization could be an objective indicator of hepatocellular reserve capacity in patients with biliary atresia, and excessive telomere shortening supports the early implementation of liver transplantation. PMID- 22311141 TI - Long-term outcomes of abdominal wall reconstruction. what are the real numbers? AB - INTRODUCTION: Advances in the acute management of the severely injured and critically ill patients have had a significant impact in survival and have increased our exposure to complex repair of large abdominal wall defects. The purpose of this article was to review the long-term (5-year or greater) outcomes of reconstruction of abdominal wall defects and the different modalities and materials currently available in the management of this challenging clinical condition. METHODS: A review of published literature. RESULTS: Our review of literature, in English language from 1984 to May 2011, identified six studies. The minimum average follow-up of the studies examined was 63 months. The hernia recurrence rate ranged from 1.1 to 16% at 5 years. A 10-year cumulative recurrence rate of 63% has been reported for suture repair and a 32% for prosthetic repair in incisional hernia. CONCLUSIONS: There is a need for long term studies of complex abdominal wall reconstruction, using biologic prosthetics mesh. PMID- 22311142 TI - Early versus delayed surgical treatment in open hand injuries: a paradigm revisited. AB - BACKGROUND: To date it remains unclear if a delayed surgical treatment of open hand injuries after more than 6 h may be detrimental to outcome. Previous investigations by McLain et al. (J Hand Surg Am 16:108-112, 1980 9), Nylen and Carlsson (Scand J Plast Reconstr Surg 14:185-189, 1991 10) could not find statistical proof of correlation between infection rate and delayed surgical treatment after open hand injuries up to 18 h. The current study was designed to investigate the outcome of early versus delayed surgical treatment after open hand injury. PATIENTS AND METHODS: A retrospective data analysis of all patients sustaining an open hand injury between January 1 and December 31 2006 was performed. Patients with incomplete data records were excluded. Patients were stratified according to time delay of surgical treatment and injury complexity. Complications, revision rate, and functional outcome were also investigated. RESULTS: Between January 1 and December 31 2006 a total of 458 patients with open hand injuries were treated at the University Hospital of Berne, Switzerland. The records were retrospectively analyzed and a subgroup of 100 patients were randomly determined for standardized follow-up evaluation. There were no significant differences regarding infection, complication, and revision rate between early (<6 h) and delayed (6-24 h) surgical treatment of open hand injuries. Independently from the time point of surgical treatment, patients with complex injuries and longer operative times had an increased infection rate (p = 0.05) and revision rate (p = 0.003). CONCLUSIONS: Delayed surgical treatment (6 24 h) of open hand injuries did not increase infection or revision rates in open non-devascularizing hand injuries. PMID- 22311143 TI - Surgical treatment of acute recurrent diverticulitis: early elective or late elective surgery. An analysis of 237 patients. AB - BACKGROUND: The optimal timing of elective surgery in diverticulitis remains unclear. We attempted to investigate early elective versus late elective laparoscopic surgery in acute recurrent diverticulitis in a retrospective study. METHOD: Data of patients undergoing elective laparoscopic surgery for diverticulitis were retrospectively gathered, including Hinchey stages I-II a/b. the primary endpoint was in-hospital complications according to the Clavien-Dindo classification. Secondary endpoints were surgical complications, operative time, conversion rate, and length of hospital stay. RESULTS: Of 237 patients, 81 (34%) underwent early elective operation (group A) and 156 (66%) underwent late elective operation (group B). In-hospital complications developed in 32% in group A and in 34% in group B (risk difference 2%, 95% Confidence Interval (95% CI): 11%, 14%). Higher age (p = 0.048) and borderline higher American Society of Anesthesiologists score (p = 0.056) were risk factors for in-hospital complications. Severe surgical complications occurred in 9% of patients in group A and 10% in group B (risk difference 2%, 95% CI: -6%, 9%). Conversion rate was 9% in group A and 3% in group B (p = 0.070). Severity of disease did not seem to have an impact on complications or length of hospital stay. The median postoperative hospital stay was 8 days in both groups (interquartile range 6-10). Mean operative time was 220 min (SD 64) in group A and 202 min (SD 48) in group B. CONCLUSIONS: This is the first study comparing early versus late elective surgery for diverticulitis in terms of the postoperative outcome using a validated classification. Although the retrospective setting and large confidence intervals don't allow definitive recommendations, these results are of utmost importance for the design of future prospective, randomized controlled trials. PMID- 22311144 TI - Autism in association with Triple X syndrome. PMID- 22311145 TI - Within-subject variability during spatial working memory in children with ADHD: an event-related potentials study. AB - Working memory (WM) dysfunction and increased within-subject variability are known issues in attention deficit/hyperactivity disorder (ADHD) patients. Little is known about the electrophysiological characteristics of this variability. We evaluated behavioral and electrophysiological within-subject variability taking developmental aspects into account in a group of ADHD patients. Multichannel (n = 31) event-related potentials (ERP) were measured during a visuo-spatial backmatching task; 44 children (8-16 years old) were tested: 22 children with ADHD, combined (n = 17) and inattentive (n = 5) type, and 22 age- and intelligence-matched control children. One-backmatching (BM1) and two backmatching (BM2) tasks were performed. Classical behavioral parameters and target and nontarget ERP were compared between groups. In addition, motor response variability and ERP amplitude variability were studied. Age-related changes in both motor response and ERP amplitude variability were analyzed in each group. Attention deficit/hyperactivity disorder children made more commission errors, which was more pronounced in the difficult (BM2) task. No difference between groups was found in ERP amplitude and in motor response variability. However, ADHD patients had higher ERP amplitude variability, which was again more pronounced in the difficult WM task. A delayed maturation of amplitude variability was seen in ADHD patients with a slower than in controls decrease in variability with age. This amplitude variability was correlated with the number of commissions, but in an opposite way for ADHD and control children. Our findings indicate an impaired visuo-spatial WM processing in ADHD children with greater ERP amplitude variability compared to controls. Our results also support the view of a delayed cortical development of visuo-spatial WM circuits in this disorder. PMID- 22311146 TI - Evolution of Internet addiction in Greek adolescent students over a two-year period: the impact of parental bonding. AB - We present results from a cross-sectional study of the entire adolescent student population aged 12-18 of the island of Kos and their parents, on Internet abuse, parental bonding and parental online security practices. We also compared the level of over involvement with personal computers of the adolescents to the respective estimates of their parents. Our results indicate that Internet addiction is increased in this population where no preventive attempts were made to combat the phenomenon from the initial survey, 2 years ago. This increase is parallel to an increase in Internet availability. The best predictor variables for Internet and computer addiction were parental bonding variables and not parental security practices. Parents tend to underestimate the level of computer involvement when compared to their own children estimates. Parental safety measures on Internet browsing have only a small preventive role and cannot protect adolescents from Internet addiction. The three online activities most associated with Internet addiction were watching online pornography, online gambling and online gaming. PMID- 22311147 TI - Predictors of responsiveness among early adolescents to a school-based risk reduction intervention over 3 years. AB - This study assesses potential predictive factors for unresponsiveness to the "Focus on Youth in the Caribbean (FOYC)" intervention using longitudinal data from 1,360 Bahamian sixth-grade youth. Results from hierarchical logistic regression analyses indicate that the intervention had a greater impact on knowledge, skills, self-efficacy, and condom use intention among low and medium initial scorers. High initial scores in knowledge, skills, self-efficacy, and intention were predictive of relative unresponsiveness to the intervention. Advanced age and male sex were predictive of unresponsiveness to the intervention for HIV/AIDS knowledge. Female gender was predictive of unresponsiveness to the intervention for self-efficacy. High academic self-evaluation was predictive of unresponsiveness to the intervention for condom use intention. The greatest intervention impact was observed at the 6-month post-intervention follow-up; these intervention-related gains were sustained over the subsequent follow-up periods. Youth with higher risk attributes (lower knowledge, skills and self efficacy) were more likely to respond to a risk reduction intervention. PMID- 22311148 TI - U.S. congregations' provision of programs or activities for people living with HIV/AIDS. AB - Using data from a nationally representative sample of U.S. congregations, this study estimates the proportion of congregations that provide programs or activities that serve people living with HIV/AIDS (PLWHA) and examines the effects of congregational characteristics on the likelihood of having them. The analysis finds that 5.6% (95% confidence interval [CI], 0.034-0.078) of U.S. congregations (roughly 18,500 (95% CI, 11,300-25,800) congregations) provide programs or activities to PLWHA. Numerous congregational characteristics increase the likelihood that congregations provide them: the presence of openly HIV positive people in the congregation, having a group that assesses their community's needs, religious tradition, and openness to gays and lesbians. By building on previous research, this study provides further information about the scope of religious congregations' involvement with PLWHA and also insight into which congregations may be willing to collaborate with other organizations to provide care for PLWHA. PMID- 22311149 TI - Predicting depression in mothers with and without HIV: the role of social support and family dynamics. AB - Many women with HIV are primary caregivers for their children. Social factors, including family dynamics, play a major role in women's depression. We hypothesized an impact of HIV seropositivity on greater depression mediated through poorer family functioning and social support. Participants include 332 Mothers Living with HIV (MLH) and 200 Neighborhood Control Mothers (NCM) recruited in Los Angeles County. The NCM were matched by neighborhood. All had children ages 6 through 20. Analyses using structural equation modeling (SEM) indicated HIV seropositivity was positively correlated with depression and negatively correlated with positive social support and effective family functioning. In a predictive path model, the relationship between having HIV and depressed mood was mediated by social support and family functioning. Findings offer explanation for increased depression resulting from HIV and social and family dynamics, and suggest innovative interventions to abate psychosocial health problems and lower risk for depression among women with HIV. PMID- 22311150 TI - High expression of nuclear survivin and Aurora B predicts poor overall survival in patients with head and neck squamous cell cancer. AB - BACKGROUND AND PURPOSE: Survivin is one of the apoptosis inhibitor proteins. Together with Aurora B, it also plays a role in regulating several aspects of mitosis. High expression of these markers is correlated with malignant behavior of various cancers and resistance to therapy. Our aim was to evaluate the prognostic role of these markers in head and neck cancers. PATIENTS AND METHODS: We evaluated the expression of Aurora B and survivin in tissue specimens of 58 patients with head and neck squamous cell carcinoma using immunohistochemistry. RESULTS: Patients who showed high expression of cytoplasmic and nuclear survivin and Aurora B had significantly shorter overall survival (p = 0.036, p < 0.000, p = 0.032, respectively). In multivariate analysis, high expression of nuclear survivin was the only independent negative prognostic factor (p = 0.024). Moreover, it was found that high co-expression of nuclear survivin and Aurora B had a negative effect on survival in univariate (p < 0.000) and multivariate (p < 0.000) analyses. CONCLUSION: The negative prognostic values of high expression of Aurora B and high co-expression of nuclear survivin and Aurora B on survival were shown. These findings suggest that co-expression of nuclear survivin and Aurora B can be useful diagnostic markers and therapeutic targets for head and neck squamous cell carcinoma. However, further studies with a larger number of patients in a more homogeneous disease group are needed to confirm the conclusion. PMID- 22311151 TI - RapidArc combined with the active breathing coordinator provides an effective and accurate approach for the radiotherapy of hepatocellular carcinoma. AB - PURPOSE: The goal of this research was to investigate the feasibility of volumetric modulated arc therapy, RapidArc (RA), in association with the active breathing coordinator (ABC) for the treatment of hepatocellular carcinoma (HCC) with radiotherapy. PATIENTS AND MATERIALS: A total of 12 patients with HCC, after receiving transcatheter arterial chemoembolization (TACE) treatment, underwent three-dimensional computer tomography (3D-CT) scanning associated with ABC using end inspiration hold (EIH), end expiration hold (EEH), and free breathing (FB) techniques. The three-dimensional conformal radiotherapy (3D-CRT), intensity modulated radiotherapy (IMRT), and RA plans (three 135 degrees arcs) were designed on different CT images, respectively. The liver volume, gross tumor volume (GTV), and planning target volume (PTV) of the three breath status and the dosimetric differences of the different plans were compared. RESULTS: There were no significant differences in the volumes of live and GTV between the three breathing techniques (p > 0.05); the PTV in FB was greater than in the EEH and EIH (p < 0.05). The overall conformality index (CI) and homogeneity index (HI) for RA (CI 0.92, HI 0.90) were better than IMRT (CI 0.90, HI 0.89) and 3D-CRT (CI 0.70, HI 0.84) for the three breathing techniques (p< 0.05). The RA and IMRT significantly reduced the mean dose, V(20), V(30), and V(40) of normal liver compared to 3D-CRT, while the V(5) and V(10) in RA were higher than in IMRT. The mean values in mean dose, V(10), V(20), V(30), and V(40) of the normal liver were reduced from 13.12 Gy, 46%, 24%, 13%, and 8% in RA(FB) to 10.23 Gy, 35%, 16%, 8%, and 5% in RA(EEH) and 9.23 Gy, 32%, 16%, 8%, and 5% in RA(EIH ), respectively. In addition, the treatment time of RA was equal to 3D-CRT, which was significantly shorter than IMRT. CONCLUSION: RA in conjunction with ABC for the treatment of HCC with radiotherapy can achieve better dose delivery and ensure the accuracy of the target volume, which spares more organs at risk, uses fewer monitor units, and shortens treatment time. PMID- 22311152 TI - Oil-sealed femtoliter fiber-optic arrays for single molecule analysis. AB - This paper describes a novel method for fabricating and sealing high-density arrays of femtoliter reaction chambers. We chemically etch one end of a 2.3 mm diameter glass optical fiber bundle to create an array of microwells. We then use a contact printing method to selectively modify the surface of the material between microwells with a hydrophobic silane. This modification makes it possible to fill the wells with aqueous solution and then seal them with a droplet of oil, forming an array of isolated reaction chambers. Individual beta-galactosidase molecules trapped in these reaction chambers convert a substrate into a fluorescent product that can be readily detected because a high local concentration of product is achieved. This binary readout can be used for ultra sensitive measurements of enzyme concentration. We observed that the percentage of wells showing enzyme activity was linearly dependent on the concentration of soluble beta-galactosidase in the picomolar range. A similar response was also observed for streptavidin-beta-galactosidase captured by biotinylated beads. These arrays are also suitable for performing single-molecule kinetics studies on hundreds to thousands of enzyme molecules simultaneously. We observed a broad distribution of catalytic rates for individual beta-galactosidase molecules trapped in the microwells, in agreement with previous studies using similar arrays that were mechanically sealed. We have further demonstrated that this femtoliter fiber-optic array can be integrated into a PDMS microfluidic channel system and sealed with oil on-chip, creating an easy to use and high-throughput device for single-molecule analysis. PMID- 22311153 TI - Wire-supported CdSe nanowire array photoelectrochemical solar cells. AB - Previous fiber-shaped solar cells are based on polymeric materials or dye sensitized wide band-gap oxides. Here, we show that efficient fiber solar cells can be made from semiconducting nanostructures (e.g. CdSe) with smaller band-gap as the light absorption material. We directly grow a vertical array of CdSe nanowires uniformly around a core metal wire and make the device by covering the top of nanowires with a carbon nanotube (CNT) film as the porous transparent electrode. The CdSe-CNT fiber solar cells show power conversion efficiencies of 1 2% under AM 1.5 illumination after the nanowires are infiltrated with redox electrolyte. We do not use a secondary metal wire (e.g. Pt) as in conventional fiber-shaped devices, instead, the end part of the CNT film is condensed into a conductive yarn to serve as the secondary electrode. In addition, our CdSe nanowire-based photoelectrochemical fiber solar cells maintain good flexibility and stable performance upon rotation and bending to large angles. PMID- 22311154 TI - Vision, action and language unified through embodiment. PMID- 22311155 TI - EEG correlates of Fitts's law during preparation for action. AB - Humans' inability to move fast and accurately at the same time is expressed in Fitts's law. It states that the movement time between targets depends on the index of difficulty, which is a function of the target width and the inter-target distance. The present study investigated the electrophysiological correlates of Fitts's law during action planning using high-density electroencephalography. Movement times were scaled according to Fitts's law, indicating that participants could not overcome the speed-accuracy trade-off during a 1-s preparation period. Importantly, the index of difficulty of the planned movement correlated linearly with the amplitudes of the cognitive N2 and P3b components, which developed during the planning period over parieto-occipital areas. These results suggest that the difficulty of a movement during action planning is represented at a level where perceptual information about the difficulty of the ensuing action is linked to motor programming of the required movement. PMID- 22311156 TI - The political ecosystem of health literacies. PMID- 22311158 TI - A database de-identification framework to enable direct queries on medical data for secondary use. AB - OBJECTIVE: To qualify the use of patient clinical records as non-human-subject for research purpose, electronic medical record data must be de-identified so there is minimum risk to protected health information exposure. This study demonstrated a robust framework for structured data de-identification that can be applied to any relational data source that needs to be de-identified. METHODS: Using a real world clinical data warehouse, a pilot implementation of limited subject areas were used to demonstrate and evaluate this new de-identification process. Query results and performances are compared between source and target system to validate data accuracy and usability. RESULTS: The combination of hashing, pseudonyms, and session dependent randomizer provides a rigorous de identification framework to guard against 1) source identifier exposure; 2) internal data analyst manually linking to source identifiers; and 3) identifier cross-link among different researchers or multiple query sessions by the same researcher. In addition, a query rejection option is provided to refuse queries resulting in less than preset numbers of subjects and total records to prevent users from accidental subject identification due to low volume of data. This framework does not prevent subject re-identification based on prior knowledge and sequence of events. Also, it does not deal with medical free text de identification, although text de-identification using natural language processing can be included due its modular design. CONCLUSION: We demonstrated a framework resulting in HIPAA Compliant databases that can be directly queried by researchers. This technique can be augmented to facilitate inter-institutional research data sharing through existing middleware such as caGrid. PMID- 22311159 TI - Effects of trace element concentrations on culturing thermophiles. AB - The majority of microorganisms in natural environments resist laboratory cultivation. Sometimes referred to as 'unculturable', many phylogenetic groups are known only by fragments of recovered DNA. As a result, the ecological significance of whole branches of the 'tree of life' remains a mystery; this is particularly true when regarding genetic material retrieved from extreme environments. Geochemically relevant media have been used to improve the success of culturing Archaea and Bacteria, but these efforts have focused primarily on optimizing pH, alkalinity, major ions, carbon sources, and electron acceptor donor pairs. Here, we cultured thermophilic microorganisms from 'Sylvan Spring' (Yellowstone National Park, USA) on media employing different trace element solutions, including one that mimicked the source fluid of the inocula. The growth medium that best simulated trace elements found in 'Sylvan Spring' produced a more diverse and faster growing mixed culture than media containing highly elevated trace element concentrations. The elevated trace element medium produced fewer phylotypes and inhibited growth. Trace element concentrations appear to influence growth conditions in extreme environments. Incorporating geochemical data into cultivation attempts may improve culturing success. PMID- 22311160 TI - Pingyangmycin downregulates the expression of EGFR and enhances the effects of cetuximab on esophageal cancer cells and the xenograft in athymic mice. AB - PURPOSE: As reported, epidermal growth factor receptor (EGFR) is over expressed in a variety of cancers including esophageal squamous cell carcinoma. Therefore, it becomes one of the potential targets for treating esophageal cancer. Pingyangmycin (PYM), a single A5 component of bleomycin, is currently used for the treatment of different types of cancers of epidermal origin, especially for head and neck cancers. In this report, the effect of PYM on EGFR expression in human esophageal cancer cells and the therapeutic efficacy of the combination of PYM and cetuximab on esophageal cancer xenograft were investigated. METHODS: The effects of PYM, cetuximab and the combination on EGFR signaling, proliferation, cell cycle, apoptosis were evaluated by using MTT, Western blotting, RT-PCR assays and flow cytometry assays, respectively, in vitro and the therapeutic efficacy by a xenograft model in athymic mice. RESULTS: Cell volume and nucleus were enlarged after PYM treatment. PYM showed potent cytotoxicity in both cell lines of Kyse-150 and Eca-109 in time and dosage-depended manner in MTT assay. PYM treatment induced G(2)/M phase arrest and apoptosis. Notably, the expression of EGFR was down-regulated by PYM in EGFR highly expression esophageal cancer cells. PYM plus cetuximab resulted in a potentiation of antiproliferative activity. PYM combined with cetuximab displayed a much higher therapeutic effect than that of the single agent on esophageal cancer xenograft in athymic mice. CONCLUSIONS: PYM could down-regulate the expression of EGFR in esophageal cancer cells and potentiate the effects of cetuximab on esophageal cancer xenograft in nude mice. The combination of PYM and cetuximab, the EGFR-targeted combination of a chemotherapeutic agent and an antibody-based drug, might be useful in cancer therapy. PMID- 22311161 TI - Phase I study of neoadjuvant chemoradiotherapy with S-1 and oxaliplatin in patients with locally advanced gastric cancer. AB - PURPOSE: The aim of this phase I study was to investigate the optimal dose of S-1 and oxaliplatin with concurrent radiotherapy in a preoperative setting for locally advanced gastric cancer. PATIENTS AND METHODS: Twelve patients with histologically confirmed clinical stage T2N+ or T3-T4 gastric adenocarcinoma received dose level -1 (oral S-1 at 60 mg/m(2)/day + oxaliplatin 40 mg/m(2) intravenously on days 1, 8, 15 and 22) or dose level 1 (S-1 80 mg/m(2)/day + oxaliplatin 40 mg/m(2)), with concurrent radiotherapy at daily fractions of 1.8 Gy 5 days per week, to a total dose of 41.4 Gy. Surgical resection, including D2 dissection, was performed within 4 weeks after the last day of chemotherapy. RESULTS: Chemoradiotherapy was generally well tolerated, with the most common dose-related grade 1 or 2 adverse events being anemia, nausea, vomiting, anorexia and abdominal pain. Two DLTs (prolonged thrombocytopenia and stomach perforation) were observed at dose level 1 (n = 6) and resulted in dose de-escalation to level -1. The recommended dose for future study is dose level -1, at which 1 of 6 patients developed grade 3 vomiting and anorexia. R0 resection was possible in 11 patients. Pathologic down-staging was observed in 6 patients, including one complete response. No clinically relevant postoperative complications occurred. CONCLUSIONS: The activity of preoperative concurrent chemoradiotherapy with S-1 (60 mg/m(2)/day for 28 consecutive days) and oxaliplatin (40 mg/m(2) on days 1, 8, 15 and 22) will be explored more extensively in a phase II study in patients with locally advanced GC. PMID- 22311163 TI - Two-dimensional strain technique to detect the function of coronary collateral circulation. AB - BACKGROUND: We aimed to evaluate the function of coronary collateral circulation (CCC) in the ischemic myocardium by a two-dimensional strain technique. METHODS AND RESULTS: Myocardial segments for all patients were divided into three groups: no coronary collateral circulation (NCCC), CCC, and normal control. We obtained the segmental strain and the strain rate in longitudinal, radial, circumferential directions, and peak rotation and rotation rate of the left ventricle by ultrasonography. Also, the time to peak of all the strain and the strain rate were acquired. The peak systolic strain, the end systolic strain, the peak systolic strain rate in the longitudinal direction, the peak systolic strain rate in the radial direction, the peak systolic strain, the end systolic strain, the peak systolic strain rate, the peak early diastolic strain rate in the circumferential direction, the peak systolic rotation rate, and the peak early diastolic rotation rate were larger for the CCC group than the NCCC group (P<0.05). Also, the time to peak of the segments was delayed for the NCCC group than for the CCC group. Receiver operating characteristic curve analysis was performed for the late diastolic strain rate in the circumferential direction to predict the presence of CCC. CONCLUSION: CCC could partially maintain the function of the related ischemic myocardium segments and prevent mechanical dyssynchrony. The two-dimensional strain technique is convenient and noninvasive for predicting the presence of CCC. PMID- 22311165 TI - Enhanced electrochemical properties of LiFePO4 by Mo-substitution and graphitic carbon-coating via a facile and fast microwave-assisted solid-state reaction. AB - A composite cathode material for lithium ion battery applications, Mo-doped LiFePO(4)/C, is obtained through a facile and fast microwave-assisted synthesis method. Rietveld analysis of LiFePO(4)-based structural models using synchrotron X-ray diffraction data shows that Mo-ions substitute onto the Fe sites and displace Fe-ions to the Li sites. Supervalent Mo(6+) doping can act to introduce Li ion vacancies due to the charge compensation effect and therefore facilitate lithium ion diffusion during charging/discharging. Transmission electron microscope images demonstrate that the pure and doped LiFePO(4) nanoparticles were uniformly covered by an approximately 5 nm thin layer of graphitic carbon. Amorphous carbon on the graphitic carbon-coated pure and doped LiFePO(4) particles forms a three-dimensional (3D) conductive carbon network, effectively improving the conductivity of these materials. The combined effects of Mo-doping and the 3D carbon network dramatically enhance the electrochemical performance of these LiFePO(4) cathodes. In particular, Mo-doped LiFePO(4)/C delivers a reversible capacity of 162 mA h g(-1) at a current of 0.5 C and shows enhanced capacity retention compared to that of undoped LiFePO(4)/C. Moreover, the electrode exhibits excellent rate capability, with an associated high discharge capacity and good electrochemical reversibility. PMID- 22311164 TI - The first step in the biosynthesis of cocaine in Erythroxylum coca: the characterization of arginine and ornithine decarboxylases. AB - Despite the long history of cocaine use among humans and its social and economic significance today, little information is available about the biochemical and molecular aspects of cocaine biosynthesis in coca (Erythroxylum coca) in comparison to what is known about the formation of other pharmacologically important tropane alkaloids in species of the Solanaceae. In this work, we investigated the site of cocaine biosynthesis in E. coca and the nature of the first step. The two principal tropane alkaloids of E. coca, cocaine and cinnamoyl cocaine, were present in highest concentrations in buds and rolled leaves. These are also the organs in which the rate of alkaloid biosynthesis was the highest based on the incorporation of 13CO2. In contrast, tropane alkaloids in the Solanaceae are biosynthesized in the roots and translocated to the leaves. A collection of EST sequences from a cDNA library made from young E. coca leaves was employed to search for genes encoding the first step in tropane alkaloid biosynthesis. Full-length cDNA clones were identified encoding two candidate enzymes, ornithine decarboxylase (ODC) and arginine decarboxylase (ADC), and the enzymatic activities of the corresponding proteins confirmed by heterologous expression in E. coli and complementation of a yeast mutant. The transcript levels of both ODC and ADC genes were highest in buds and rolled leaves and lower in other organs. The levels of both ornithine and arginine themselves showed a similar pattern, so it was not possible to assign a preferential role in cocaine biosynthesis to one of these proteins. PMID- 22311162 TI - Biologic therapies in the treatment of psoriasis: a comprehensive evidence-based basic science and clinical review and a practical guide to tuberculosis monitoring. AB - The treatment of psoriasis has undergone a revolution with the advent of biologic therapies including infliximab, etanercept, adalimumab, efalizumab, golimumab, certolizumab, alefacept, secukinumab, abatacept, and ustekinumab. These medications are designed to target specific components of the immune system and are a major technological advancement over traditional immunosuppressive medications. Herein, we present a comprehensive, unbiased comparison of these medications focusing on their differences. For example, TNF antagonists can differ in the way they are dissolved and administered, the effector molecules they can bind, serum peak and trough levels, the types of intracellular signals they can induce, the in vivo complexes that they can form, their protein structure, and their incidence and timing of rare adverse events, among other things. A critical review of the clinical studies that have tested the efficacy of these molecules is also presented including head-to-head comparison trials. The safety of biologics in terms of their long-term adverse events is discussed, as is their use in different types of psoriasis and in different patient populations. Finally, all anti-TNF agents have been associated with a variety of serious and "routine" opportunistic infections, particularly tuberculosis. For this reason, anti-tuberculosis testing both prior to the initiation of a biologic therapy and annually during treatment is pertinent. The uses and limitations of both the tuberculin skin test (TST) and QuantiFeron(r)-TB Gold (QFT) are discussed, as is the care of patients who present with latent tuberculosis infection prior to the initiation of biologic therapy. Recommendations for tuberculosis monitoring are provided. PMID- 22311166 TI - Pulmonary alveolar microlithiasis: a case report and review of the literature. AB - A 12-year-old girl of Turkish descent was referred 6 weeks after an influenza A infection because of persistent chest X-ray abnormalities compatible with interstitial lung disease. The clinically suspected diagnosis of pulmonary alveolar microlithiasis (PAM) supported by pathognomonic radiological abnormalities was confirmed by genetic analysis. The clinical presentation of PAM is illustrated by a case and review of the current literature on this subject: you only see what you know. PMID- 22311167 TI - Nutritional status and its relationship with blood pressure among children and adolescents in South China. AB - The present study measures the nutritional status and the blood pressure to assess their relationship in a group of children and adolescents in the Hainan province, China. A total of 5,456 students aged 7 to 18 years were recruited from 10 public schools in Hainan province of South China during the period March 2009 to December 2009. Height, weight, systolic blood pressure, and diastolic blood pressure were measured by health-care professionals. Body mass index (BMI) was calculated and used to define thinness, overweight, and obesity according to the existing standards. Prevalence of thinness, overweight, obesity, pre hypertension, and hypertension was computed, and logistical regression model was used to examine the association of BMI with elevated blood pressure. A high prevalence of thinness was observed in male and female children and adolescents (34.0% and 34.3%, respectively). The percentage of overweight and obesity was 2.7% and 1.3%, respectively. Pre-hypertension and hypertension were detected in 3.9% and 3.3% children and adolescents, respectively. Multivariate logistical regression analysis showed that obesity was positively associated with both pre hypertension and hypertension, with adjusted odds ratio of 1.44 (95% confidence interval (CI) = 1.08-1.92, P = 0.014) and 2.00 (95%CI = 1.53-2.60, P < 0.001) compared to normal weight students. Overweight was also associated with pre hypertension and hypertension. However, no significant association between thinness and pre-hypertension and hypertension was found. In conclusion, this study showed that thinness, especially mild thinness, was a major public health problem among children and adolescents in Hainan province of South China. Overweight and obesity were strongly associated with pre-hypertension and hypertension among studied students. PMID- 22311168 TI - Vitamin D deficiency and calcium intake in reference to increased body mass index in children and adolescents. AB - Vitamin D deficiency has been linked to several chronic diseases in adults. Studies focusing on children and adolescents, however, are limited. In this randomized cross-sectional study, we aimed to determine the prevalence of vitamin D deficiency and its relationship with childhood obesity and dietary calcium intake among a population of healthy urban Saudi children and adolescents. To achieve this, 331 randomly selected Saudi children (53.8% females and 46.2% males) aged 6-17 years were included. Demographic, medical, and dietary information were collected; anthropometrics were measured. Levels of serum fasting glucose, lipid profile, 25(OH) D, and for albumin corrected calcium were analyzed. Vitamin D deficiency was noted in all subjects, with girls having significantly lower vitamin D levels than boys. Mean calcium intake was found to be 60% of the required dietary allowance (RDA), while the mean vitamin D intake was 23% of RDA. Vitamin D status and calcium intake were comparable in both normal and overweight/obese children and adolescents. Vitamin D status was highest among children who had calcium intake >800 mg/day. In adolescents there was insignificant but decreasing trend in BMI, which was observed to be highest among those whose calcium intake was <250 mg/day and lowest among those taking >800 mg/day. CONCLUSION: results from this study suggest the importance of vitamin D fortification and increased dietary calcium in the Saudi diet to meet RDA requirements and avoid onset of vitamin D deficiency-related diseases in Saudi children and adolescents. PMID- 22311169 TI - Droplet-based interfacial capacitive sensing. AB - This paper presented a novel droplet-based pressure sensor using elastic and capacitive electrode-electrolyte interfaces to achieve ultrahigh mechanical-to electrical sensitivity (1.58 MUF kPa(-1)) and resolution (1.8 Pa) with a simple device architecture. The miniature transparent droplet sensors, fabricated by one step laser micromachining, consisted of two flexible polymer membranes with conductive coating and a separation layer hosting a sensing chamber for an electrolyte droplet. The sensing principle primarily relied on high elasticity of the sensing droplet and large capacitance presented at the electrode-electrolyte interface. A simple surface modification scheme was introduced to the conductive coating, which reduced hysteresis of the droplet deformation without substantially compromising the interfacial capacitance. Moreover, the major concern of liquid evaporation was addressed by a mixture of glycerol and electrolyte with long-term stability in a laboratory environment. Theoretical analyses and experimental investigations on several design parameters (i.e., the dimensions of the sensing chamber and the droplet size) were thoroughly conducted to characterize and optimize the overall sensitivity of the device. Moreover, the environmental influences (e.g., temperature and humidity) on the capacitive measurement were further investigated. Finally, the simply constructed and mechanically flexible droplet sensor was successfully applied to detect minute blood pressure variations on the skin surface (with the maximum value less than 100 Pa) throughout cardiovascular cycles. PMID- 22311170 TI - Mayak workers study cohort. An inter-institutional comparison of causes of death in the cause-of-death register of Ozyorsk in the Russian Federation. AB - BACKGROUND: The cause-of-death register at the Southern Urals Biophysics Institute (SUBI), Ozyorsk, Russia, was established to document the number and causes of deaths in the Mayak workers cohort, which includes all persons (N = 22,377) employed at Mayak nuclear facility between 1948 and 1982. Most workers were occupationally exposed to high doses of ionizing radiation and have been shown to have increased risks of various chronic diseases including cancer. OBJECTIVES: To investigate the quality of cause of death coding in the SUBI register. METHODS: A random sample of 246 deaths (~1% of the total) was coded independently at the SUBI and the Danish Cancer Society using the International Classification of Diseases 9 (ICD-9). Proportions of matching codes were calculated. RESULTS: Overall, 233 deaths (95%) were identically classified using the ICD-9 main category matching. Excluding mismatches that were considered to be incorrectly coded during validation, the validity of the register increased to 98%. Using the specific ICD-9 first three-digit matching, 182 deaths were identically coded (74%) and the respective validity of the register was 85%. There were also some non-resolvable discrepancies demonstrating limitations of assigning one code for each death or using language-adapted ICD-9 version. CONCLUSIONS: This validation study was an important quality check of a register used for mortality follow-up in a highly influential epidemiological study on radiation-related health effects. The results of the inter-institutional comparison were generally favourable; however, since the comparison revealed individual mismatches and some systematically differing coding practices, it is essential to repeat it on a regular basis in order to maintain a high quality. PMID- 22311171 TI - Microevolution of Pseudomonas aeruginosa to a chronic pathogen of the cystic fibrosis lung. AB - Pseudomonas aeruginosa is the leading pathogen of chronic cystic fibrosis (CF) lung infection. Life-long persistance of P. aeruginosa in the CF lung requires a sophisticated habitat-specific adaptation of this pathogen to the heterogeneous and fluctuating lung environment. Due to the high selective pressure of inflamed CF lungs, P. aeruginosa increasingly experiences complex physiological and morphological changes. Pulmonary adaptation of P. aeruginosa is mediated by genetic variations that are fixed by the repeating interplay of mutation and selection. In this context, the emergence of hypermutable phenotypes (mutator strains) obviously improves the microevolution of P. aeruginosa to the diverse microenvironments of the CF lung. Mutator phenotypes are amplified during CF lung disease and accelerate the intraclonal diversification of P. aeruginosa. The resulting generation of numerous subclonal variants is advantegous to prepare P. aeruginosa population for unpredictable stresses (insurance hypothesis) and thus supports long-term survival of this pathogen. Oxygen restriction within CF lung environment further promotes persistence of P. aeruginosa due to increased antibiotic tolerance, alginate production and biofilm formation. Finally, P. aeruginosa shifts from an acute virulent pathogen of early infection to a host adapted chronic virulent pathogen of end-stage infection of the CF lung. Common changes that are observed among chronic P. aeruginosa CF isolates include alterations in surface antigens, loss of virulence-associated traits, increasing antibiotic resistances, the overproduction of the exopolysaccharide alginate and the modulation of intermediary and micro-aerobic metabolic pathways (Hogardt and Heesemann, Int J Med Microbiol 300(8):557-562, 2010). Loss-of-function mutations in mucA and lasR genes determine the transition to mucoidity and loss of quorum sensing, which are hallmarks of the chronic virulence potential of P. aeruginosa. Metabolic factors that are positively selected in response to the specific environment of CF lung include the outer membrane protein OprF, the microaerophilic oxidase Cbb3-2, the blue copper protein azurin, the cytochrome c peroxidase c551 and the enzymes of the arginine deiminase pathway ArcA-ArcD. These metabolic adaptations probably support the growth of P. aeruginosa within oxygen-depleted CF mucus. The deeper understanding of the physiological mechanisms of niche specialization of P. aeruginosa during CF lung infection will help to identify new targets for future anti-pseudomonal treatment strategies to prevent the selection of mutator isolates and the establishment of chronic CF lung infection. PMID- 22311172 TI - An electrochemical signal 'off-on' sensing platform for microRNA detection. AB - The abnormal expression of microRNAs (miRNAs) in many solid tumors makes miRNAs potential biomarkers for disease diagnosis and highlights the need for the sensitive and selective detection of miRNAs. In the present work, an 'off-on' signaling genosensor platform for miRNA-21 detection was well developed. This tactic was based on a locked nucleic acid-integrated nucleic acid hairpin probe, a biotin-labeled bridge DNA-AuNPs-bio-barcode signal amplification unit and enzymatic signal amplification. The test is simple, fast and ultrasensitive with a linear range of 0.01-700 pM. The detection limit was estimated to be 6 fM. The overexpression of miRNA-21 was confirmed in total RNA extracted from human hepatocarcinoma cells BEL-7402 and human HeLa cells compared with the control sample extracted from normal human hepatic L02 cells. This method does not need miRNA-21 labeling, isolation, enrichment or PCR amplification. The performance of the assay developed here could satisfy the need for rapid, easy, sensitive and specific early cancer diagnosis in clinical diagnostics. PMID- 22311173 TI - Lower expression of ATM and gene deletion is more frequent in adrenocortical carcinomas than adrenocortical adenomas. AB - Adrenocortical carcinoma (ACC) is a rare endocrine malignancy accounting for approximately 0.02-0.2% of all cancer deaths. The molecular pathogenesis of ACC has been the hot topic of recent reviews but it is still poorly understood. It is imperative to have a better understanding on the pathophysiology of ACC so as to establish precise diagnosis and effective treatment. This study aims to identify the molecular markers between ACCs and adrenocortical adenomas (ACAs). With MLPA, we checked on 10 ACA and 9 ACC tissue samples. The MLPA results showed deletion on chromosomes 18q, 11q, 11p, and 13q and duplication on chromosomes 3q, 4q, 6p, and 19p. There was a significant difference in the number of aberration copies of the ataxia telangiectasia-mutated (ATM) gene located on chromosome 11q22-q23 between ACCs and ACAs. Five out of 9 (56%) ACC specimens had deletion of ATM (P = 0.011). RT-PCR result then demonstrated that ATM mRNA level is lower in ACCs than in ACAs (P < 0.001). In addition, immunohistochemistry (IHC) study of the 19 ACA and 18 ACC samples confirmed lower expression of ATM protein in ACCs than in ACAs (P < 0.001). The study demonstrated that ATM expression was diminished in ACC than in ACA, suggesting an important role of ATM in the tumorigenesis of ACC. PMID- 22311174 TI - Mini-review: new therapeutic options in hypoparathyroidism. AB - Hypoparathyroidism is a disorder characterized by hypocalcemia and low or absent parathyroid hormone (PTH). While standard treatment of hypoparathyroidism consists of oral calcium and vitamin D supplementation, maintaining serum calcium levels can be a challenge, and concerns exist regarding hypercalciuria and ectopic calcifications that can be associated with such treatment. Hypoparathyroidism is the only classic endocrine deficiency disease for which the missing hormone, PTH, is not yet an approved treatment. This mini-review focuses on the use of PTH in the treatment of hypoparathyroidism. There are two available formulations of PTH: teriparatide [human PTH(1-34)] and the full-length molecule, PTH(1-84). Both PTH(1-34) and PTH(1-84) lower supplemental vitamin D requirements and increase markers of bone turnover. Densitometric and histomorphometric studies in some subjects treated with PTH(1-84) demonstrate improvement in abnormal bone-remodeling dynamics and return of bone metabolism toward normal euparathyroid levels. Further detailed examination of skeletal features following therapy with the different treatment regimens and data regarding the effect of PTH on quality of life measures are under active investigation. PMID- 22311175 TI - Approaches for non-invasive assessment of endothelial function: focus on peripheral arterial tonometry. AB - The arterial endothelium is a complex organ that modulates vascular tone by release of various substances to control perfusion. Endothelial function reflects vascular ageing and health. Already at the earliest stages of atherosclerosis the delicate balance between arterial constriction and relaxation is disturbed. Therefore, non-invasive assessment of endothelial function is a means to identify patients at increased cardiovascular risk, even at levels of disease that cannot be identified with classical imaging techniques that depict arterial wall and/or lumen or with functional assessment of ischaemia. Currently, there is an increasing interest in the early recognition of endothelial dysfunction to streamline and optimise preventive therapeutic measures. In this article, several methods for the assessment of endothelial function are briefly reviewed. In particular, we discuss the fast bed-side assessment of endothelial function by the reactive hyperaemia peripheral arterial tonometry (RH-PAT) method. PMID- 22311176 TI - Long-term outcomes of isolated aortic valve replacement and concomitant AVR and coronary artery bypass grafting. AB - BACKGROUND: It is well established that concomitant aortic valve replacement (AVR) and coronary artery bypass grafting (CABG) has a higher operative mortality rate than isolated AVR. However, studies report conflicting results on the long term mortality. The aim of this prospective study was to explore and compare the outcomes and risk factors of isolated AVR and concomitant AVR and CABG in a consecutive Dutch patient population. METHODS: From January 2001 through January 2010, 332 consecutive patients underwent AVR with or without CABG at a single institution (197 isolated AVR and 135 concomitant AVR and CABG). A multivariate Cox proportional hazard analysis was performed to determine the independent risk factors for long-term mortality after aortic valve replacement. RESULTS: All 332 consecutive, referred patients who underwent aortic valve surgery were followed for up to 10 years. Median follow-up length was 48 months. The population had a median age of 73 years (IQR 65-78) and predominantly consisted of males (62%). Patients in the combined AVR and CABG group were older, had worse cardiac risk profiles and had worse preoperative cardiac statuses than those receiving isolated AVR. Five-year survival was 85% in AVR and 73% in AVR-CABG (p-value 0.012). Independent risk factors for mortality were higher creatinine values, previous CABG and increasing age. CONCLUSION: Unselected, consecutive patients who underwent aortic valve replacement surgery and who received concomitant bypass surgery between 2001-2010 had higher 5-year mortality than their counterparts without CABG. Prior CABG, renal function, age but not concomitant CABG remained independently associated with increased mortality. Finally, the observed mortality rate in this consecutive patient group compared favourably with preoperative risk assessment using the EuroSCORE. PMID- 22311181 TI - [University ambulatory care centers can expand their health services]. PMID- 22311178 TI - Preventing alcohol use with a voluntary after-school program for middle school students: results from a cluster randomized controlled trial of CHOICE. AB - There are many mandated school-based programs to prevent adolescent alcohol and drug (AOD) use, but few are voluntary and take place outside of class time. This cluster randomized controlled trial evaluates CHOICE, a voluntary after-school program for younger adolescents, which reduced both individual- and school-level alcohol use in a previous pilot study. We evaluated CHOICE with 9,528 students from 16 middle schools. The sample was 51% female; 54% Hispanic, 17% Asian, 15% white, 9% multiethnic and 3% African American. Fifteen percent of students attended CHOICE. All students completed surveys on alcohol beliefs and use at baseline and 6-7 months later. We conducted intention-to-treat (ITT) school-level analyses and propensity-matched attender analyses. Lifetime alcohol use in the ITT analysis (i.e., school level) achieved statistical significance, with an odds ratio (OR) of 0.70 and a NNT of 14.8. The NNT suggests that in a school where CHOICE was offered, 1 adolescent out of 15 was prevented from initiating alcohol use during this time period. Although not statistically significant (p = .20), results indicate that past month alcohol use was also lower in CHOICE schools (OR = 0.81; NNT = 45). Comparisons of attenders versus matched controls yielded results for lifetime use similar to school-wide effects (OR = 0.74 and NNT = 17.6). Initial results are promising and suggest that a voluntary after-school program that focuses specifically on AOD may be effective in deterring alcohol use among early adolescents; however, further research is needed as program effects were modest. PMID- 22311182 TI - High sensitivity three-dimensional insulator-based dielectrophoresis. AB - Insulator-based dielectrophoresis (iDEP) is a very promising technique for sorting microparticles based on their electrical properties. The need for microfabricated electrode arrays is eliminated by using constrictions in a microchannel to induce large electric field gradients. In this work, micro milling is used to build devices with three-dimensional features that exhibit very large constriction ratios. These three-dimensional insulator-based dielectrophoresis (3DiDEP) devices allow for trapping microparticles at average electric fields one order of magnitude lower than two-dimensional designs with the same footprint. Low voltage operation minimizes Joule heating effects that have limited previous systems, opening up the possibility for new biological applications of iDEP. PMID- 22311183 TI - Changes in the expression of plasma proteins associated with thrombosis in BRCA1 mutation carriers. AB - PURPOSE: Although BRCA1 gene mutations have been associated with breast cancer, BRCA1 mutations have been also involved in other functions. Thrombosis and coagulation are novel mechanisms recently associated with cancer. The aims of the present study were (a) to evaluate, using proteomics, if BRCA1 mutation carriers have a different plasma proteins expression related to thrombosis and coagulation profile than non-mutant BRCA1 women and (b) to analyze if the expression of these proteins may be different among BRCA1 mutation carriers with and without breast cancer. METHODS: Proteomic study was based on 2-dimensional electrophoresis and mass spectrometry. The study was performed in 10 BRCA1 non-mutant controls and 21 women with BRCA1 mutations (with breast cancer (n = 8) and breast cancer-free (n = 13)), all of them free of family history or diagnosis of ovarian cancer. RESULTS: Proteomic study showed that fibrinogen gamma chain isotypes 2 and 3, serotransferrin isotype 4, and convertase C3/C5 isotypes 1-5 were significantly increased in plasma from BRCA1 mutation carriers with respect to BRCA1 non-mutant controls. Plasma levels of alpha-1 antitrypsin isotypes 2-5, apolipoprotein A-IV, and vitamin D-binding protein isotypes 1 and 2 were significantly reduced in BRCA1 mutation carriers with respect to non-mutant controls. Only apolipoprotein A-IV plasma levels were significantly higher in cancer-free BRCA1 mutations carriers compared with BRCA1 mutations carriers who developed breast cancer. CONCLUSION: It is suggested that independently of breast cancer generation, BRCA1 encoded gene alterations are associated with changes in the expression of circulating proteins associated with thrombosis and coagulation. PMID- 22311184 TI - A novel xenograft model with intrinsic vascularisation for growing undifferentiated pleomorphic sarcoma NOS in mice. AB - PURPOSE: Preclinical development of antisarcoma therapy is primarily based on the subcutaneous transplantation of sarcoma xenografts. Tumour cell survival remains a hurdle of current models, which has been attributed to the hypoxic conditions following transplantation. We hypothesised that sarcoma models with an intrinsic tissue-engineered vascular supply are easily reproducible. The aim of this study was to establish a novel vascularised xenograft model. MATERIALS AND METHODS: Primary human soft tissue sarcomas were transplanted into a silicon chamber and placed around the superficial epigastric vessels of nude mice. Sarcoma xenograft samples were assessed histomorphologically. RESULTS: All sarcoma xenografts engrafted, leading to solid tumours. Histological, immunohistochemical staining and light/electron microscopy confirmed the xenografts as identical high-grade pleomorphic sarcomas (NOS) compared with the original patients' tumours. CONCLUSION: This novel sarcoma xenograft model with an intrinsic vascular supply could be of high value for studying human soft tissue sarcomas and their therapy. PMID- 22311185 TI - Identification and characterization of an indigo-producing oxygenase involved in indole 3-acetic acid utilization by Acinetobacter baumannii. AB - Acinetobacter baumannii harbours a gene cluster similar to the iac locus of Pseudomonas putida 1290, which can catabolize the plant hormone indole 3-acetic acid (IAA) as an energy source. However, there has been no evidence showing that IAA can be utilized by A. baumannii. This study showed that A. baumannii can grow in M9 minimal medium containing IAA as the sole carbon source. A mutagenesis study indicated that iacA, encoded in the iac locus of A. baumannii, is involved in the catabolism of IAA. As shown by western blotting analysis, the IacA protein was detected in A. baumannii grown in M9 minimal medium with IAA but not with pyruvate, suggesting that the expression of iacA is regulated by the presence of IAA. In vitro studies have shown that IacA can oxidize indole, an IAA-like molecule, converting it to indoxyl, which spontaneously dimerises to form indigo. In this study, we show that the crude extracts from either wild-type A. baumannii or Escherichia coli overexpressing IacA can oxidize IAA. These results imply that the iac gene cluster of A. baumannii is involved in IAA degradation and that the iacA gene is upregulated when cells encounter IAA in their native environments. PMID- 22311186 TI - Bioinformatic and experimental fishing for artemisinin-interacting proteins from human nasopharyngeal cancer cells. AB - Determining interacting cellular partners of drugs by chemical proteomic techniques is complex and tedious. Most approaches rely on activity-based probe profiling and compound-centric chemical proteomics. The anti-malarial artemisinin also exerts profound anti-cancer activity, but the mechanisms of action are incompletely understood. In the present investigation, we present a novel approach to identify artemisinin-interacting target proteins. Our approach overcomes usual problems in traditional fishing procedures, because the drug was attached to a surface without further chemical modification. The proteins identified effect among others, cell cycle arrest, apoptosis, inhibition of angiogenesis, disruption of cell migration, and modulation of nuclear receptor responsiveness. Furthermore, a bioinformatic approach confirmed experimentally identified proteins and suggested a large number of other interacting proteins. Theoretically predicted interaction partners may serve as a starting point to complete the whole set of proteins binding artemisinin. PMID- 22311187 TI - Biomedical informatics publications: a global perspective. Part II: Journals. AB - BACKGROUND: Biomedical Informatics (BMI) is a broad discipline, having evolved from both Medical Informatics (MI) and Bioinformatics (BI). An analysis of publications in the fieldshould provide an indication about the geographic distribution of BMI research contributions and possible lessons for the future, both for research and professional practice. OBJECTIVES: In part I of our analysis of biomedical informatics publications we presented results from BMI conferences. In this second part, we analyse BMI journals, which provide a broader perspective and comparison between data from conferences and journals that ought to confirm or suggest alternatives to the original distributional findings from the conferences. METHODS: We manually collected data about authors and their geographical origin from various MI journals: the International Journal of Medical Informatics (IJMI), the Journal of Biomedical Informatics (JBI), Methods of In formation in Medicine (MIM) and The Journal of the American Medical Informatics Association (JAMIA). Focusing on first authors, we also compared these findings with data from the journal Bioinformatics. RESULTS: Our results confirm those obtained in our analysis of BMI conferences - that local and regional authors favor their corresponding MI journals just as they do their conferences. Consideration of other factors, such as the increasingly open source nature of data and software tools, is consistent with these findings. CONCLUSIONS: Our analysis suggests various indicators that could lead to further, deeper analyses, and could provide additional insights for future BMI research and professional activities. PMID- 22311188 TI - Images in endocrine pathology: spindle cell lesion of the thyroid gland. PMID- 22311190 TI - Effects of organic farming and genotype on alimentary and nutraceutical parameters in tomato fruits. AB - BACKGROUND: In recent years there has been growing interest in the influence of sustainable cultivation systems on the biochemical quality of vegetables. In this study, two genotypes of tomato, Giulianova and Perbruzzo, were grown in both organic (Or) and conventional (Conv) systems for three years and harvested at commercial ripening in each year. The Conv system was established according to traditional techniques and the Or system according to current EU regulations. Samples were evaluated for volatile substances, sugars, organic acids, dry matter, pH and lycopene. RESULTS: During the three years, volatile substances increased in Or samples of Giulianova, while this response was less evident in Perbruzzo. Other parameters of both genotypes were not influenced by Or cultivation. Lycopene content in both Conv-cultivated genotypes was constant during the whole experimental period. In Or samples, lycopene content was lower than in Conv samples during the first and second years. In the last year, lycopene content in Or samples of Giulianova was similar to that in Conv samples, while lycopene content in Or samples of Perbruzzo was higher than that in Conv samples. CONCLUSION: Changes in biochemical parameters of tomato fruits could be affected by both cultivation system and genotype, with a significant increase in both volatile substances and lycopene in the 2010 crop. PMID- 22311191 TI - Relationships of personality factors to perceived stress, depression, and oral lichen planus severity. AB - BACKGROUND: PURPOSE: The objective of this study is to examine relationships of hardiness and big five personality factors to depression, perceived stress, and oral lichen planus (OLP) severity. METHOD: Sixty Iranian patients with oral lichen planus completed measures of perceived stress, hardiness, big five, and depression. RESULTS: Linear regressions revealed that control and challenge significantly predicted least perceived stress. On the contrary, big five factor of neuroticism predicted more perceived stress. Furthermore, control, commitment, and extraversion negatively predicted depression levels, but neuroticism positively predicted depression levels. Additionally, more levels of the challenge factor predicted fewer OLP scores while more levels of perceived stress predicted more OLP scores. CONCLUSION: The components of control challenge and neuroticism factors had a significant role in predicting perceived stress. On the other hand, the components of control and commitment and extraversion factors had a prominent role in predicting depression in patients with OLP, so personality constructs may have an effective role in triggering experience of stress, depression, and OLP itself. Additionally, interventions that enhance individual protective factors may be beneficial in reducing stress and depression in some severe diseases. PMID- 22311192 TI - Severe myopic anisometropia in a Chinese family. AB - PURPOSE: The aim of this study is to describe a Chinese four-generation family with severe myopic anisometropia and to explore the possible pathogenesis for this disease. METHODS: Eighteen individuals of a four-generation family participated in the study, including a pair of monozygotic (MZ) twins. A detailed family history and clinical data were recorded. All participants were subjected to ophthalmologic examinations including refractive error, slitlamp, and fundus examination. B-scan and A-scan ultrasonography were additionally ordered for each affected patient for further evaluation. Optical refractive correction was prescribed, and full-time occlusion therapy of 6 days weekly in right eye and 1 day weekly in left eye was prescribed for the MZ twins. RESULTS: Five individuals were affected with severe myopic anisometropia within this family, including the pair of MZ twins. In all affected individuals, the right eyes were more myopic than the left eyes, and axial length and anterior chamber depth measurements in the more myopic eyes were longer. After 6 months of therapy, the best corrected visual acuity in the amblyopic eye of the MZ twins improved significantly. CONCLUSIONS: The co-occurrence of severe myopic anisometropia in five individuals of the family supports a genetic basis for the disease. The successful therapeutic effect on anisometropic amblyopia highlights the importance of early detection and timely treatment. PMID- 22311193 TI - Aberrations and topography in normal, keratoconus-suspect, and keratoconic eyes. AB - PURPOSE: This study was designed to compare higher order aberrations of the cornea and of the eye with inferior-superior (I-S) corneal topographic values in keratoconic eyes. METHODS: We studied 92 eyes from 78 subjects: 21 eyes of 14 subjects with suspected keratoconus, 23 eyes of 16 subjects with manifest keratoconus, and 48 eyes of 48 subjects without keratoconus using the L80 wave+, an instrument which can measure corneal topography and aberrations simultaneously with a large dynamic range making it possible to evaluate higher order aberrations to the seventh order of the Zernike polynomial function series. RESULTS: All ocular and corneal higher order aberrations were found to be significantly higher for keratoconic than normal eyes, but for suspected keratoconus the results were mixed. Corneal aberrations were higher than ocular aberrations due to compensation from the internal aberrations. For manifest keratoconus, the corneal and ocular vertical coma displayed the largest difference being 38.6 and 78.5 times higher, respectively, than normal eyes, while the largest differences for suspected keratoconus were only 5.3 and 4.0 times higher, respectively. On the other hand, inferior-superior dioptric asymmetry was 9.4 and 37.3 times higher for suspected keratoconus and keratoconic eyes, respectively, than normal eyes. The separation of normality curves between suspected keratoconus and normal eyes was 28.6% for I-S and 14.3% for both corneal vertical coma and corneal total coma. CONCLUSIONS: Although corneal vertical coma and, to a lesser extent, ocular vertical coma were found to be good indicators for the detection of keratoconic eyes, the traditional corneal topographic value such as the inferior-superior dioptric asymmetry remains an important predictor for identifying suspected keratoconus. However, ocular vertical coma and ocular higher order total root mean square also represent a good means of identifying suspected keratoconus. PMID- 22311194 TI - Diet and feeding behavior of Rhinopithecus brelichi at Yangaoping, Guizhou. AB - Expectations of increases in human population growth and accelerated habitat loss, along with the realization that efforts to provide protection for ecosystems that sustain primates have met with limited success, make it critical that conservation plans are grounded firmly in scientific observation. Studies of the diet breadth and feeding behavior of endangered species, therefore, are critical for understanding ecological adaptations and developing a conservation strategy. The diet and feeding ecology of gray snub-nosed monkeys (Rhinopithecus brelichi) were studied in the Fanjingshan National Nature Reserve, Guizhou, China. The monkeys were found to consume 107 different species of trees, shrubs, and ground plants from 58 genera and 28 families. Food items included young leaves, mature leaves, flowers, fruits/seeds, buds, and insects. Among these food items, there were at least 13 evergreen species of tree and liana, 3 species of grasses, and at least 2 kinds of invertebrates collected from decayed wood. Diet varied markedly throughout different seasons. Overall, diet composition (based on feeding records) was 15.3% buds, 25.5% young leaves, 21.8% mature leaves, 9.4% flowers, 21.6% fruits/seeds, and 6.3% other items. The monkeys feed mainly on young leaves and flowers in spring, unripe fruits/seeds and young leaves in summer, ripe fruits/seeds in autumn, and mature leaves and buds in winter. We propose that when inhabiting forests of lower elevation and greater vegetation complexity, R. brelichi is characterized by expanded diet breadth and includes a greater diversity of food types and plant species in its diet. One food type that appears critical to the diet of this species, especially during the winter, are the buds of Magnolia sprengeri. To protect this resource we advocate working with local communities to limit the collection of M. sprengeri, which is used in traditional Chinese medicine and has high economic value for people in the reserve. PMID- 22311195 TI - What life cycle graphs can tell about the evolution of life histories. AB - We analyze long-term evolutionary dynamics in a large class of life history models. The model family is characterized by discrete-time population dynamics and a finite number of individual states such that the life cycle can be described in terms of a population projection matrix. We allow an arbitrary number of demographic parameters to be subject to density-dependent population regulation and two or more demographic parameters to be subject to evolutionary change. Our aim is to identify structural features of life cycles and modes of population regulation that correspond to specific evolutionary dynamics. Our derivations are based on a fitness proxy that is an algebraically simple function of loops within the life cycle. This allows us to phrase the results in terms of properties of such loops which are readily interpreted biologically. The following results could be obtained. First, we give sufficient conditions for the existence of optimisation principles in models with an arbitrary number of evolving traits. These models are then classified with respect to their appropriate optimisation principle. Second, under the assumption of just two evolving traits we identify structural features of the life cycle that determine whether equilibria of the monomorphic adaptive dynamics (evolutionarily singular points) correspond to fitness minima or maxima. Third, for one class of frequency dependent models, where optimisation is not possible, we present sufficient conditions that allow classifying singular points in terms of the curvature of the trade-off curve. Throughout the article we illustrate the utility of our framework with a variety of examples. PMID- 22311196 TI - Variable elimination in post-translational modification reaction networks with mass-action kinetics. AB - We define a subclass of chemical reaction networks called post-translational modification systems. Important biological examples of such systems include MAPK cascades and two-component systems which are well-studied experimentally as well as theoretically. The steady states of such a system are solutions to a system of polynomial equations. Even for small systems the task of finding the solutions is daunting. We develop a mathematical framework based on the notion of a cut (a particular subset of species in the system), which provides a linear elimination procedure to reduce the number of variables in the system to a set of core variables. The steady states are parameterized algebraically by the core variables, and graphical conditions for when steady states with positive core variables imply positivity of all variables are given. Further, minimal cuts are the connected components of the species graph and provide conservation laws. A criterion for when a (maximal) set of independent conservation laws can be derived from cuts is given. PMID- 22311197 TI - Chemopreventive effects of free and bound phenolics associated to steep waters (nejayote) obtained after nixtamalization of different maize types. AB - Free and bound phenolics extracts from nejayote solids were obtained after optimally lime-cooking blue, normal white, red, normal yellow, high-carotenoid and quality protein maize types. The extraction yield ranged from 4.47 to 10.05%. Bound phenolics extracts had higher content of total phenolics, antioxidant activity and ferulic acid compared to the free phenolics extracts. In general, free phenolics extracts were less cytotoxic than the bound phenolics counterparts. Bound phenolics extracts had higher induction of quinone reductase (QR) and particularly the normal yellow nejayote exerted the highest chemopreventive index tested in Hepa1c1c7 cells. When tested for monofunctional phase 2 induction capacity in BPrc1 cells, the bound phenolics extracts of blue, normal white and quality protein nejayotes were better inducers than the normal yellow counterpart. Particularly, the free phenolics extract of the white maize nejayote induced BPrc1 cells QR and exerted a higher chemopreventive index compared to the bound phenolics extract. Therefore, the nejayote of the normal white maize was the best source of monofunctional phase 2 enzyme inducers. PMID- 22311198 TI - [CAPD in 2nd-graders of primary schools: which tests discriminate normal from impaired children?]. AB - BACKGROUND: Third- and fourth-graders with (C)APD can be differentiated from non (C)APD children at best by means of 3 diagnostic tests (Nickisch & Kiese-Himmel, 2009). Now it should be examined which tests discriminate second graders with (C)APD from those without. MATERIAL UND METHODS: 10 audiological and psychometrical tests were used for this purpose. PATIENTS: 33 second-graders of primary schools diagnosed with auditory-specific perceptual deficits (clinical group (C)APD: average age: 7.8; SD 0.7 years) were compared to 48 normally developed children of the same school grade (control group Non-(C)APD: average age: 7.6; SD 0.5 years). RESULTS: With the exception of 3 non-language based tests significant group-differentiations appeared, with the (C)APD-children displaying worse results. The diagnostic classification succeeded in the following test-combination: Word-Understanding in Background Noise (Goettinger Sprachaudiometrie im Freifeld), Dichotic Listening (Uttenweiler Test), Numerical Sequence Memory (Subtest of the German version of the Illinois Test of Psycholinguistic Abilities), Nonword Repetition (Mottier-Test). 97.5% of all children were assigned to the correct diagnostic group (96.3% after cross validation). CONCLUSION: After the exclusion of neurological disorders, peripheral hearing-disorders as well as intelligence-impairments the diagnostic assurance of (C)APD of second-graders succeeded, permitting very small probability of error. Compared to the preliminary study, an additional diagnostic test on second-graders is necessary; classification, as a result, will be more precise. PMID- 22311199 TI - [Eucharist bacteria brought miserey--bilateral parotitis led to emergency tracheotomy]. PMID- 22311200 TI - [Globus sensation and intermittently reduced movement of the right vocal cord]. PMID- 22311201 TI - [Indications of intraoperative ultrasound in head and neck surgery]. AB - BACKGROUND: A possible use of B-scan sonography arises from the difficulty in transferring information by means of imaging to the intraoperative situation, which is now possible with navigation systems in complicated surgical procedures in the field of otolaryngology. A solution to this problem offers the intraoperative use of ultrasonography for orientation in soft tissue surgery. PATIENTS AND METHOD: A prospective study involving 115 patients in total entailed scanning with a small part linear and fingertip probe with either 10 and 7.5 MHZ. An ultrasound endoscope featuring a 7.5 MHZ convex probe was used to image endolarygeal processes. RESULTS: Indications included panendoscopies, parotidectomies, submandibulectomies, lymph node exstirpations and abscess incisions. The colour doppler sonography was used in reconstructive surgery involving microvascular transplants. The display of soft tissue tumours provided information about tumour size as well as demarcation or infiltration of neighbouring structures. The fingertip probe and the ultrasound endoscopy served to evaluate areas that were morphologically difficult to access. After clamping the radial artery when harvesting the forearm flap, a sufficient perfusion of the thumb and later the sufficiency of the vascular anastomosis could be verified. CONCLUSION: The intraoperative use of sonography is an inexpensive non-invasive procedure that can be performed by the surgeon himself and allows quick and reliable orientation during difficult operations. PMID- 22311202 TI - Physiological responses induced by emotion-eliciting films. AB - Emotion-eliciting films are commonly used to evoke subjective emotional responses in experimental settings. The main aim of the present study was to investigate whether a set of film clips with discrete emotions were capable to elicit measurable objective physiological responses. The convergence between subjective and objective measures was evaluated. Finally, the effect of gender on emotional responses was investigated. A sample of 123 subjects participated in the study. Individuals were asked to view a set of emotional film clips capable to induce seven emotions: anger, fear, sadness, disgust, amusement, tenderness and neutral state. Skin conductance level (SCL), heart rate (HR) and subjective emotional responses were measured for each film clip. In comparison with neutral films, SCL was significantly increased after viewing fear films, and HR was also significantly incremented for anger and fear films. Physiological variations were associated with arousal measures indicating a convergence between subjective and objective reactions. Women appeared to display significantly greater SCL and HR responses for films inducing sadness. The findings suggest that physiological activation would be more easily induced by emotion-eliciting films that tap into emotions with higher subjective arousal such as anger and fear. PMID- 22311203 TI - Do personalized feedback messages about activity patterns stimulate patients with chronic low back pain to change their activity behavior on a short term notice? AB - The aim of this study was to explore whether patients responded to personalized messages on top of continuous visual feedback by changes in activity patterns and whether this response is related to the stages of change and the pain intensity levels. Patients wore a movement sensor and a PDA for 2 weeks and received continuously feedback and time-related messages to influence activity behavior. The response was calculated by calculating the activity 30 min before and after a message. In addition, the readiness to change was measured with the Stage of Change questionnaire and pain intensity was measured on a visual analogue scale. Sixteen patients participated, receiving a total of 517 messages. Overall, patients responded to personalized messages (p < .049), with a higher response in the morning. Patients in different stages of change responded differently to the messages (p = .009) and the response was significantly related to the pain intensity levels (Pearson correlation -.226) in the second week of feedback. This study suggests that personalized messages have the potential to influence activity behavior. It seems relevant to take time of the day, the stages of change and pain intensity levels of the patient into account to further optimize the feedback strategy used. PMID- 22311204 TI - Prefrontal neuromodulation using rTMS improves error monitoring and correction function in autism. AB - One important executive function known to be compromised in autism spectrum disorder (ASD) is related to response error monitoring and post-error response correction. Several reports indicate that children with ASD show reduced error processing and deficient behavioral correction after an error is committed. Error sensitivity can be readily examined by measuring event-related potentials (ERP) associated with responses to errors, the fronto-central error-related negativity (ERN), and the error-related positivity (Pe). The goal of our study was to investigate whether reaction time (RT), error rate, post-error RT change, ERN, and Pe will show positive changes following 12-week long slow frequency repetitive TMS (rTMS) over dorsolateral prefrontal cortex (DLPFC) in high functioning children with ASD. We hypothesized that 12 sessions of 1 Hz rTMS bilaterally applied over the DLPFC will result in improvements reflected in both behavioral and ERP measures. Participants were randomly assigned to either active rTMS treatment or wait-list (WTL) groups. Baseline and post-TMS/or WTL EEG was collected using 128 channel EEG system. The task involved the recognition of a specific illusory shape, in this case a square or triangle, created by three or four inducer disks. ERN in TMS treatment group became significantly more negative. The number of omission errors decreased post-TMS. The RT did not change, but post-error RT became slower. There were no changes in RT, error rate, post-error RT slowing, nor in ERN/Pe measures in the wait-list group. Our results show significant post-TMS differences in the response-locked ERP such as ERN, as well as behavioral response monitoring measures indicative of improved error monitoring and correction function. The ERN and Pe, along with behavioral performance measures, can be used as functional outcome measures to assess the effectiveness of neuromodulation (e.g., rTMS) in children with autism and thus may have important practical implications. PMID- 22311205 TI - [Acetylsalicylic acid protects against solid tumors]. PMID- 22311206 TI - Enhancement of adipogenic and osteogenic differentiation of human bone-marrow derived mesenchymal stem cells by supplementation with umbilical cord blood serum. AB - Umbilical cord blood serum (UCBS) is a promising replacement for animal sera for the culture of human mesenchymal stem cells (hMSC), the unique serum composition of UCBS appearing to have variable effects on their proliferation and differentiation. Conditioning UCBS with methods such as charcoal stripping assists specific processes such as adipogenesis and osteogenesis in hMSCs. The charcoal stripping of serum removes lipophilic materials such as oestrogens, which are known inhibitors of adipogenesis. hMSC cultures supplemented with charcoal-stripped UCBS (CS-UCBS) show enhanced adipogenesis in adipogenic induction medium (AIM) containing indomethacin, 3-isobutyl-1-methylxanthine and dexamethasone. To obtain efficient adipogenesis without CS-UCBS, we have developed a modified protocol in which cells cultured separately with UCBS and CS UCBS are constantly treated with minimal doses of insulin (1.1 MUg/ml) for 10 days prior to the addition of AIM. hMSC cultures differentiated by using the modified protocol show improved adipogenesis under fetal bovine serum (FBS), UCBS and CS-UCBS conditions, with levels of adipogenesis being highest in UCBS, thereby eliminating the need for charcoal stripping. Furthermore, in each of the three sera, the insulin-pre-treated hMSCs accumulate lipid droplets faster and exhibit improved adipogenesis overall when compared with normal AIM-induced adipogenesis. We have also compared the levels of osteogenesis in hMSCs by using an induction medium devoid of dexamethasone. Maximum calcium deposition has been observed in hMSCs cultured with UCBS, as compared with those cultured with FBS or CS-UCBS. Our newly developed methods with a humanized serum supplement thus enhance the differentiation of cultured hMSCs. PMID- 22311207 TI - The Nogo-66 receptor family in the intact and diseased CNS. AB - The Nogo-66 receptor family (NgR) consists in three glycophosphatidylinositol (GPI)-anchored receptors (NgR1, NgR2 and NgR3), which are primarily expressed by neurons in the central and peripheral mammalian nervous system. NgR1 was identified as serving as a high affinity binding protein for the three classical myelin-associated inhibitors (MAIs) Nogo-A, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp), which limit axon regeneration and sprouting in the injured brain. Recent studies suggest that NgR signaling may also play an essential role in the intact adult CNS in restricting axonal and synaptic plasticity and are involved in neurodegenerative diseases, particularly in Alzheimer's disease pathology through modulation of beta-secretase cleavage. Here, we outline the biochemical properties of NgRs and their functional roles in the intact and diseased CNS. PMID- 22311208 TI - Attention deficit hyperactivity disorder and dyslexia: a history of overlap. PMID- 22311209 TI - Periodic electroencephalographic patterns: usefulness of definition and classification. PMID- 22311210 TI - Association study between functional polymorphisms in the TNF-alpha gene and obsessive-compulsive disorder. AB - Obsessive-compulsive disorder (OCD) is a prevalent psychiatric disorder of unknown etiology. However, there is some evidence that the immune system may play an important role in its pathogenesis. In the present study, two polymorphisms (rs1800795 and rs361525) in the promoter region of the cytokine tumor necrosis factor-alpha (TNFA) gene were genotyped in 183 OCD patients and in 249 healthy controls. The statistical tests were performed using the PLINK((r)) software. We found that the A allele of the TNFA rs361525 polymorphism was significantly associated with OCD subjects, according to the allelic chi(2) association test (p=0.007). The presence of genetic markers, such as inflammatory cytokines genes linked to OCD, may represent additional evidence supporting the role of the immune system in its pathogenesis. PMID- 22311211 TI - Performance patterns in Conners' CPT among children with attention deficit hyperactivity disorder and dyslexia. AB - This study investigated the performance of children with attention deficit hyperactivity disorder (ADHD) and dyslexia using Conners' Continuous Performance Test (CCPT). The clinical groups were composed of 52 children with ADHD and 32 children with dyslexia. Performance in the CCPT was evaluated using ANCOVA to compare the clinical groups with the normative Brazilian sample. The ADHD group performed worse than the normative sample in almost all of the measurements, except for reaction time and response style. The dyslexia group scored higher on commissions, variability, perseverations and inconsistency in the reaction time over the six time blocks (Hit SE Block Change) than the children in the normative Brazilian sample. The ADHD and dyslexia groups differed in omission measurements, Hit RT SE, variability, perseverations, Hit RT Interstimulus Intervals (ISI) Change and Hit SE ISI Change. We thus found that the dyslexia group had specific deficit patterns, with greater response to non-target stimuli, greater perseveration and response variability, and difficulties in hit reaction time as the test progressed. PMID- 22311212 TI - Central nervous system lymphoma: magnetic resonance imaging features at presentation. AB - OBJECTIVE: This paper aimed at studying presentations of the central nervous system (CNS) lymphoma using structural images obtained by magnetic resonance imaging (MRI). METHODS: The MRI features at presentation of 15 patients diagnosed with CNS lymphoma in a university hospital, between January 1999 and March 2011, were analyzed by frequency and cross tabulation. RESULTS: All patients had supratentorial lesions; and four had infra- and supratentorial lesions. The signal intensity on T1 and T2 weighted images was predominantly hypo- or isointense. In the T2 weighted images, single lesions were associated with a hypointense signal component. Six patients presented necrosis, all of them showed perilesional abnormal white matter, nine had meningeal involvement, and five had subependymal spread. Subependymal spread and meningeal involvement tended to occur in younger patients. CONCLUSION: Presentations of lymphoma are very pleomorphic, but some of them should point to this diagnostic possibility. PMID- 22311213 TI - The prevalence of multiple sclerosis in Belo Horizonte, Brazil. AB - Investigations on the prevalence rates of multiple sclerosis (MS) around the world have yielded important clues on the interplay between genetic susceptibility and environmental factors. As Brazil is a huge country laid on many latitudes and inhabited by population with distinct ethnic backgrounds, it might be assumed that the frequency of MS varies in its different regions. OBJECTIVE: To determine the prevalence rate of MS in Belo Horizonte, the capital of the State of Minas Gerais, Southeastern Brazil. METHODS: We used six sources to draw up a provisional list of identified cases of MS. Only patients with diagnosis of clinically definite MS according to Poser Committee criteria were included. RESULTS: The calculated crude MS prevalence was 18.1/100,000 inhabitants. CONCLUSIONS: The MS prevalence in Belo Horizonte is similar to that found in Sao Paulo and Botucatu, two other cities in southeastern Brazil with similar ethnic background. PMID- 22311214 TI - The effect of social support on the quality of life of patients with multiple sclerosis. AB - OBJECTIVE: To determine the predictive value of social support on health related quality of life (HRQoL) in multiple sclerosis (MS) patients. METHODS: The sample is composed by 150 MS consecutive patients. We used the Medical Outcomes Study Social Support Survey to assess social support and the Health Status Questionnaire to assess HRQoL. For inferential analysis, we used the Multiple Linear Regression with stepwise selection of variables. RESULTS: The age, basic education, psychological support and disability explains 41.6% of the variance in physical function, 29.4% in physical performance and 30.6% in emotional performance. Age and psychological support explains 23.1% of the variance in physical function and 29.4% in vitality. CONCLUSION: This study demonstrated that social support is a predictor with a significant effect on HRQoL in MS. PMID- 22311215 TI - Metabolic syndrome and dementia associated with Parkinson's disease: impact of age and hypertension. AB - OBJECTIVE: To determine correlations between age and metabolic disorders in Parkinson's disease (PD) patients. METHODS: This observational cross-sectional study included brief tests for dementia and the Mattis test. Signals of metabolic syndrome were evaluated. RESULTS: There was no significant effect from the presence of hypertension (OR=2.36 for patients under 65 years old and OR=0.64 for patients over 65), diabetes or hypercholesterolemia regarding occurrences of dementia associated with PD (24% of the patients). The study demonstrated that each year of age increased the estimated risk of dementia in PD patients by 9% (OR=1.09; 95%CI: 1.01-1.17). CONCLUSION: There was no evidence to correlate the presence of metabolic syndrome with the risk of dementia that was associated with PD. The study confirmed that dementia in PD is age dependent and not related to disease duration. PMID- 22311216 TI - Impact of changes in balance and walking capacity on the quality of life in patients with Parkinson's disease. AB - Parkinson's disease (PD) is characterized by motor symptoms that cause the decline of functional capacity and affect the quality of life (QoL). OBJECTIVE: To evaluate the impact of changes in balance and walking capacity on the PD. METHODS: The instruments used were: Unified Parkinson's Disease Rating Scale (UPDRS), modified Hoehn and Yahr Scale (HY), Schwab and England scale (SE), quality of life questionnaire (PDQ-39), Berg balance Scale (BBS) and six-minute walk test (6MWT). RESULTS: Thirty-six patients with mean disease duration of 7.3 years were assessed. Lower scores on the BBS and shorter distances walked during the 6MWT correlated with a poorer perception of QoL. This correlation occurred at the expense of the mobility and daily living activities domains. CONCLUSION: Our results indicated that the impairment in balance while performing functional activities and the reduction in walking capacity are important factors that negatively affect the perception of QoL in PD patients. PMID- 22311217 TI - Central pain due to stroke: cognitive representation and coping according to gender. AB - OBJECTIVE: To identify and compare perceptions of pain and how it is faced between men and women with central post-stroke pain. METHODS: The participants were 25 men and 25 women of minimum age 30 years-old and minimum schooling level of four years, presenting central post-stroke pain for at least three months. The instruments used were: Mini-Mental State Examination; structured interview for the Brief Psychiatric Scale; Survey of Sociodemographic and Clinical Data; Visual Analogue Scale (VAS); Ways of Coping with Problems Scale (WCPS) in Scale; Revised Illness Perception Questionnaire (IPQ-R); and Beck Depression Inventory (BDI). RESULTS: A significantly greater number of women used the coping strategy "Turn to spiritual and religious activities" in WCPS. They associated their emotional state with the cause of pain in IPQ-R. "Distraction of attention" was the strategy most used by the subjects. CONCLUSION: Women used spiritual and religious activities more as a coping strategy and perceived their emotional state as the cause of pain. PMID- 22311218 TI - Language disorders and brain lesion topography in aphasics after stroke. AB - Aphasia is a language disorder associated with focal brain lesions. Although the topographic definition of the language area has been widely accepted, there is not necessarily any direct correlation between the lesion site and the manifested symptoms. OBJECTIVE: To analyze aspects of language in aphasics in relation to lesion topography. METHODS: A prospective, descriptive study of qualitative nature was conducted on 31 individuals, aged older than 15 years, with at least three years of schooling, and a confirmed diagnosis of stroke. Language assessment was carried out using the Montreal Toulouse battery (alpha version), Boston naming test, and FAS test. Language test results were compared against lesion topography findings from magnetic resonance imaging. RESULTS: Heterogeneous results were found when comparing topography with aphasia, non aphasia, and performance on language scales. CONCLUSION: No direct relationship was evident between lesion topography, aphasia, and language test performance. PMID- 22311219 TI - Hyperglycemia in nondiabetic patients during the acute phase of stroke. AB - OBJECTIVE: To determine patterns of hyperglycemic (HG) control in acute stroke. METHODS: Anonymous survey through Internet questionnaire. Participants included Latin-American physicians specialized in neurocritical care. RESULTS: The response rate was 74%. HG definition varied widely. Fifty per cent considered it when values were >140 mg/dL (7.8 mmol/L). Intravenous (IV) regular insulin was the drug of choice for HG correction. One fifth of the respondents expressed adherence to a protocol. Intensive insulin therapy (IIT) was used by 23%. Glucose levels were measured in all participants at admission. Routine laboratory test was the preferred method for monitoring. Reactive strips were more frequently used when monitoring was intensive. Most practitioners (56.7%) monitored glucose more than two times daily throughout the Intensive Care Unit stay. CONCLUSIONS: There is considerable variability and heterogeneity in the management of elevated blood glucose during acute phase of stroke by the surveyed Latin-American physicians. PMID- 22311220 TI - Quality of life issues and occupational performance of persons with epilepsy. AB - Epilepsy causes restrictions in the performance of various daily activities. The aiming of this study was to investigate whether these restrictions affect the perceived quality of life. The assessments Quality of Life in Epilepsy-31 (QOLIE 31) and Canadian Occupational Performance Measure (COPM) were applied in a sample that consisted of a single group of 34 subjects with at least two years of uncontrolled seizures. The results indicated that the most affected domains of QOLIE-31 were seizure worry, 29.77 (+/-21.72), and effects of drugs, 49.75 (+/ 28.58), and for the COPM, the average of performance and satisfaction were respectively 3.10 (+/-3.07) and 4.45 (+/-3.29), and performance limitations most frequently cited were maintain employment (18), left home alone (15) and courses (15). The application of the Spearman correlation coefficient showed that the three main performance limitations posed by the COPM, especially regarding the level of satisfaction, influence the perception of quality of life. Thus, occupational performance proves to be an important area of intervention with subjects with epilepsy. PMID- 22311221 TI - Periodic EEG patterns: importance of their recognition and clinical significance. AB - Periodic electroencephalographic (EEG) patterns consist of discharges usually epileptiform in appearance, which occur at regular intervals, in critical patients. They are commonly classified as periodic lateralized epileptiform discharges (PLEDs), bilateral independent PLEDs or BIPLEDs, generalized epileptiform discharges (GPEDs) and triphasic waves. Stimulus-induced rhythmic, periodic or ictal discharges (SIRPIDs) are peculiar EEG patterns, which may be present as periodic discharges. The aim of this study is to make a review of the periodic EEG patterns, emphasizing the importance of their recognition and clinical significance. The clinical significance of the periodic EEG patterns is uncertain, it is related to a variety of etiologies, and many authors suggest that these patterns are unequivocally epileptogenic in some cases. Their recognition and classification are important to establish an accurate correlation between clinical, neurological, laboratorial and neuroimaging data with the EEG results. PMID- 22311222 TI - Acquired cerebellar ataxia due to statin use. PMID- 22311223 TI - Echogenicity of the substantia nigra region in Parkinson's disease. PMID- 22311224 TI - Vasculitic neuropathy following influenza seasonal vaccination. PMID- 22311225 TI - Spinal melanotic schwannomas. PMID- 22311226 TI - Long-term, low-dose immunosuppression for myasthenia does not affect collateral, asymptomatic sclerosing cholangitis. PMID- 22311227 TI - Rare case of carotid artery occlusion due to thrombosis of a giant cerebral aneurysm: the role of cerebral revascularization. PMID- 22311228 TI - Unilateral non traumatic vertebral artery dissection with cervical spinal cord infarction. PMID- 22311229 TI - Transcranial Doppler pulsatility index: what it is and what it isn't. AB - BACKGROUND: Transcranial Doppler (TCD) pulsatility index (PI) has traditionally been interpreted as a descriptor of distal cerebrovascular resistance (CVR). We sought to evaluate the relationship between PI and CVR in situations, where CVR increases (mild hypocapnia) and decreases (plateau waves of intracranial pressure ICP). METHODS: Recordings from patients with head-injury undergoing monitoring of arterial blood pressure (ABP), ICP, cerebral perfusion pressure (CPP), and TCD assessed cerebral blood flow velocities (FV) were analyzed. The Gosling pulsatility index (PI) was compared between baseline and ICP plateau waves (n = 20 patients) or short term (30-60 min) hypocapnia (n = 31). In addition, a modeling study was conducted with the "spectral" PI (calculated using fundamental harmonic of FV) resulting in a theoretical formula expressing the dependence of PI on balance of cerebrovascular impedances. RESULTS: PI increased significantly (p < 0.001) while CVR decreased (p < 0.001) during plateau waves. During hypocapnia PI and CVR increased (p < 0.001). The modeling formula explained more than 65% of the variability of Gosling PI and 90% of the variability of the "spectral" PI (R = 0.81 and R = 0.95, respectively). CONCLUSION: TCD pulsatility index can be easily and quickly assessed but is usually misinterpreted as a descriptor of CVR. The mathematical model presents a complex relationship between PI and multiple haemodynamic variables. PMID- 22311231 TI - Attitudes in the general population towards hemi-craniectomy for middle cerebral artery (MCA) infarction. A population-based survey. AB - BACKGROUND: Decompressive hemicraniectomy reduces mortality after space-occupying MCA infarction. Data on the general public's opinion toward interventions that can save lives but leave the survivors impaired are lacking. METHODS: In this population-based epidemiological study in a German city, we surveyed 312 adults in a telephone interview. Here, we presented a scenario of a space-occupying MCA infarct. We evaluated probands' attitude toward decompressive surgery in general, and toward outcome scenarios according to Rankin scale (RS) definitions. RESULTS: 312 persons (157 women, 52 +/- 20 years) were interviewed. 58 persons had difficulty comprehending the proposed scenario, most of them being of advanced age (79 +/- 5 years). From the remaining 254 responders 5 (2%) persons favoured surgical intervention, 149 (58%) were undecided, and 100 (39%) were opposed to surgery. The number of individuals opting for surgery rose in scenarios with a better outcome: If very severe impairment was anticipated (RS 5), only 3 (1%) persons favored surgery. With severe (RS 4), moderate (RS3), and slight impairment (RS2) the numbers were at 16 (6%), 60 (24%), and 161 (63%), respectively. We found no association with age, sex, religion, education, self estimated health status, or marital status. CONCLUSIONS: Explaining complex medical situations to laypersons poses a major problem, particularly to those of old age. Only a minority favors life-saving medical interventions if survival is associated with deficits of unpredictable degree. The majority of persons does not favor intervention even if only moderate impairment is anticipated. Decompressive surgery may in fact be against the values of many individuals. PMID- 22311230 TI - Determinants of central sympathetic activation in spontaneous primary subarachnoid hemorrhage. AB - BACKGROUND: Subarachnoid hemorrhage (SAH) has been associated with pronounced acute sympathetic activation. The purpose of this investigation is to identify demographic, clinical, radiological, and anatomical features of SAH that relate to sympathetic activation. METHODS: Observational study of consecutive Grades 3-5 SAH patients requiring ventriculostomy and undergoing endovascular aneurysmal obliteration. All patients underwent cerebrospinal fluid (CSF) sampling within 48 h of SAH onset, and samples were assayed for various catecholamine compounds and metabolites. Univariate analyses were performed to identify variables associated with catecholamine levels, and to correlate linearity among catecholamine compounds and metabolites. Variables demonstrating a possible association and variables of interest were entered into linear regression models to determine predictors of catecholamine elevations. RESULTS: Of the 102 patients, mean age was 58 years and 74% were female; 42% were Hunt-Hess (H/H) grade 4/5, 61% had a computed tomography (CT) score of 3/4, 57% had anterior cerebral or communicating artery (ACA/ACom) aneursysms, and 23% had aneurysms in the posterior circulation. In the univariate analysis, age, gender, H/H grade, CT score, and aneurysm location demonstrated various associations with catecholamine levels, and substantial positive correlations existed between the various catecholamine compounds and metabolites. Linear regression analyses revealed H/H grade to be an independent predictor of elevated CSF epinephrine (EPI), 3,4 dihydroxyphenylalanine (DOPA) and 3,4-dihydroxyphenyl acetic acid (DOPAC) levels, and of the norepinephrine/3,4-dihydroxyphenylglycol (NE/DHPG) ratio (p < 0.05 for all analyses). Female gender independently predicted increased dopamine (DA) and DOPAC levels (p < 0.05 for two analyses), as well as possibly DOPA levels (p < 0.1). Age, CT score and aneurysm location demonstrated only inconsistent associations and trends. CONCLUSIONS: Central sympathetic activation relates to clinical severity and female gender. No definitive associations were found for age, hemorrhage amount, or aneurysm location. PMID- 22311232 TI - Angioedema after tPA: what neurointensivists should know. AB - BACKGROUND: Angioedema is an underappreciated and potentially life-threatening complication of intravenous (IV) recombinant tissue plasminogen activator (rt PA). Patients taking angiotensin converting enzyme (ACE) inhibitors are at increased risk of this rare complication. METHODS: Case report. RESULTS: A 74 year-old woman taking lisinopril for hypertension was treated with IV rt-PA for right hemispheric acute ischemic stroke. Shortly after completion of the rt-PA infusion, she developed asymmetric angioedema involving the tongue and left lower lip. No emergent airway intervention was needed. Following treatment with epinephrine, antihistamines, and corticosteroids, the edema resolved within 24 h. The patient made an excellent recovery from the ischemic stroke. CONCLUSIONS: Orolingual angioedema can complicate rt-PA treatment of acute stroke and is often ipsilateral to the side of hemiparesis. Neurointensivists should be aware of this possibility, which is increased in patients taking ACE inhibitors. Epinephrine can be given safely in this scenario. Identification of high risk features may help guide decisions regarding early definitive airway management. PMID- 22311233 TI - Impact of interhospital transfer on complications and outcome after intracranial hemorrhage. AB - BACKGROUND: Interhospital transfer of patients with intracranial hemorrhage can offer improved care, but may be associated with complications. METHODS: A prospective single-center study was conducted between 2/2008 and 6/2010 of patients with subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH) and subdural hemorrhage (SDH), admitted to the neuro-ICU at a tertiary-care academic hospital. Admission demographics, complications and 3-month functional outcomes were compared between directly admitted and transferred patients. The effect of transfer time on complications and outcomes was assessed. RESULTS: Of 257 total patients, 120 (47%) were transferred and 137 (53%) were directly admitted. About 86 (34%) had SAH, 80 (31%) had ICH and 91 (35%) had SDH. The median transfer time was 190 min (46-1,446). Transferred patients were significantly less educated, less likely to be insured and more frequently had SAH as a diagnosis than directly admitted patients (all P < 0.05), though admission neurological and cognitive status was similar. Complications did not differ between transferred and directly admitted patients; however, among transferred patients, longer transfer time was associated with aneurysm rebleed (7.3 vs. 1.8%, P = 0.007) and tracheostomy (20 vs. 17.5%, P = 0.013). In multivariate analysis, after adjusting for other predictors, transferred patients had worse cognitive outcome at 3 months (adjusted OR 12.4, 95% CI 1.2-125.2, P = 0.033) compared to direct admits, though there were no differences in death, disability or length of stay (LOS). CONCLUSIONS: Transferred patients had similar rates of death, disability and LOS as directly admitted patients, though worse 3-month cognitive outcomes. Prolonged time to interhospital transfer was associated with an increased risk of aneurysm rerupture and tracheostomy. PMID- 22311234 TI - Treatment of intracerebral hemorrhage with tranexamic acid after thrombolysis with tissue plasminogen activator. AB - BACKGROUND: Thrombolytic treatment with intravenous tissue plasminogen activator (i.v. tPA) is the only FDA-approved therapy for acute ischemic stroke. There are risks associated with thrombolytics, including intracranial and extracranial hemorrhage and hypersensitivity reactions. Established treatment for post-tPA hemorrhage includes administration of blood products including cryoprecipitate, fresh frozen plasma, and platelets which have poorly established efficacy. Tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA) have been studied as hemostatic therapies in post-operative hemorrhage, menorrhagia, intracranial hemorrhage (ICH), subarachnoid hemorrhage, and trauma patients. There is no reported literature on the use of TXA to reverse thrombolytic therapy with tPA. METHODS: This is a case report of a Jehovah's Witness patient who was unwilling to receive blood products after developing symptomatic ICH following i.v. tPA. He consequently received TXA for reversal of thrombolytic therapy. RESULTS: The patient received a total of 1.675 g of i.v. TXA within 3 h of finishing the iv tPA. Repeat brain imaging with computed tomography and magnetic resonance imaging revealed no further expansion of hemorrhages. CONCLUSION: TXA is an inexpensive medication which competitively inhibits the activation of plasminogen and can be given to reverse thrombolysis in the setting of hemorrhage after i.v. thrombolytic therapy. PMID- 22311235 TI - The "time" to timely predict ischemic deficit after subarachnoid hemorrhage. PMID- 22311236 TI - The relationship between ghrelin and adiponectin levels in breast milk and infant serum and growth of infants during early postnatal life. AB - Ghrelin and adiponectin have been found in breast milk and are considered to take part in the regulation of growth and energy metabolism of infants. Our aims were to determine ghrelin and adiponectin levels in breast milk and serum samples of mothers and their infants, and to investigate the relationship between their levels and anthropometry of newborn infants during early postnatal life. Total and active ghrelin and adiponectin levels were studied in breast milk, and the serum samples of 25 healthy lactating women and their healthy fullterm infants were taken at the 1st and 4th months of life. Anthropometric measurements of infants were also performed during the study period. Breast milk and infant serum active ghrelin levels were found to be significantly increased at the 4th month of life compared with 1st month levels (p < 0.05). Maternal serum total ghrelin and infant serum adiponectin levels were found to be significantly reduced at the 4th month of life (p < 0.05). Breast milk active ghrelin levels were higher than the infant and maternal serum active ghrelin at the 1st and 4th months (p < 0.05). There was a negative significant correlation between the level of infant serum active ghrelin levels and BMI of infants at the 1st month. A positive significant correlation was found between the level of 1st month infant serum adiponectin levels and weight gain of infants during the study period. Fourth month infant serum adiponectin were also positively correlated with weight and BMI of infants at the 4th month and the weight gain during study period. There was a positive significant correlation between the level of 4th month breast milk active ghrelin and weight gain of infants during the study period. Ghrelin and adiponectin are involved in postnatal growth of infants. Ghrelin in breast milk also seems to be related to the growth of infants during early postnatal life. The sources of these peptides in breast milk are probably both maternal serum and breast tissue itself. PMID- 22311238 TI - Call to action: sharing our case management resources in case of an event. AB - Disasters happen. Disaster drills are geared to bring out the worst and best of an organization's preparedness. Case management departments can be prepared, but sharing our thoughts, procedures, and resources can benefit all. PMID- 22311237 TI - Gene-environment interactions on growth trajectories. AB - It has been suggested that children with larger brains tend to perform better on IQ tests or cognitive function tests. Prenatal head growth and head growth in infancy are two crucial periods for subsequent intelligence. Studies have shown that environmental exposure to air pollutants during pregnancy is associated with fetal growth reduction, developmental delay, and reduced IQ. Meanwhile, genetic polymorphisms may modify the effect of environment on head growth. However, studies on gene-environment or gene-gene interactions on growth trajectories have been quite limited partly due to the difficulty to quantitatively measure interactions on growth trajectories. Moreover, it is known that assessing the significance of gene-environment or gene-gene interactions on cross-sectional outcomes empirically using the permutation procedures may bring substantial errors in the tests. We proposed a score that quantitatively measures interactions on growth trajectories and developed an algorithm with a parametric bootstrap procedure to empirically assess the significance of the interactions on growth trajectories under the likelihood framework. We also derived a Wald statistic to test for interactions on growth trajectories and compared it to the proposed parametric bootstrap procedure. Through extensive simulation studies, we demonstrated the feasibility and power of the proposed testing procedures. We applied our method to a real dataset with head circumference measures from birth to age 7 on a cohort currently being conducted by the Columbia Center for Children's Environmental Health (CCCEH) in Krakow, Poland, and identified several significant gene-environment interactions on head circumference growth trajectories. PMID- 22311239 TI - Wake me up for the tsunami: Canadian case managers navigate the tricky waters of aging and ageism in health care. PMID- 22311240 TI - Evaluating the effectiveness of an aggressive case management and home telehealth monitoring program for long-term control of A1C. AB - PURPOSE/OBJECTIVES: To describe and assess the effectiveness of a case management and home telemonitoring program for patients with diabetes mellitus (DM) PRIMARY PRACTICE SETTING: Case managers work in a mid-sized medical center for the Department of Veterans Affairs. Patients are veterans who participate in a home telemonitoring and case management program designed to assist with long-term control of serum glucose levels. FINDINGS/CONCLUSIONS: The home telemonitoring/case management program process is shown to be effective in helping patients with long-term control of glycosylated hemoglobin (A1C). When compared with a control group, program participants showed significantly differentiated long-term improvement in A1C levels. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: * Home telemonitoring and aggressive case management together are effective in helping patients with diabetes self-care. * Case management practices for patients with diabetes should include a strong educational component, continuing throughout the process, that addresses lifestyle and dietary changes. * Home telemonitoring may serve as a patient "demand" indicator and workload regulator for case managers. * Case management and home telemonitoring have long-term effects in diabetes self-care even after active case management and home telemonitoring come to an end. PMID- 22311242 TI - Case management needs of older and elderly cancer survivors. AB - PURPOSE/OBJECTIVES: The purpose of this study was to examine the case management needs of older and elderly adults. The specific aim was to describe the results of a survey distributed to cancer survivors, asking them to respond to questions about their specific needs. The survey targeted the physical, psychosocial, social, and spiritual needs. PRIMARY PRACTICE SETTING: Outpatient setting, outreach program. FINDINGS/CONCLUSIONS: Fatigue, fear of reoccurrence, and sleep disturbances were of the greatest concern to the older and elderly cancer survivor. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: Case managers dealing with elderly cancer survivors can target these needs in terms of transitions from inpatient to outpatient care and beyond into the survivorship period. PMID- 22311244 TI - An integrative review of case management for diabetes. AB - PURPOSE/OBJECTIVES: The purpose of this integrative review is to examine the effectiveness of case management for improving health outcomes in patients with diabetes mellitus as found in the literature from 2000 to 2010. PRIMARY PRACTICE SETTING: Diabetes case management in health care settings. FINDINGS/CONCLUSIONS: Case management is an effective intervention for glycemic control and is cost effective. Evidence is building for its use in primary care. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: Case management can be an important intervention for diabetes care in primary care and community settings. With evidence at the level of rigor of randomized controlled trials, case management significantly improved biophysiological, psychosocial, preventive, and adherence outcomes. Thus, case management can be an important aspect of effectiveness in health care services delivery within a reconfigured delivery system. PMID- 22311245 TI - Pooling our knowledge to maintain a "gold standard". PMID- 22311246 TI - We all benefit when the team is "engaged". PMID- 22311247 TI - POLST: something new has been added. PMID- 22311248 TI - Just stuck! Managing ambivalence and resistance to going back to work, part 1. PMID- 22311249 TI - Insight into evidence-based return to work guidelines. PMID- 22311250 TI - Health-related quality-of-life status in Veterans with spinal disorders. AB - PURPOSE: To measure the impact of spinal disorders on health-related quality of life (HRQOL) among Veterans, to describe demographic patterns of Veterans with spinal disorders, and to quantify HRQOL scores as they relate to demographics, medical comorbidities, pain severity, and depressive symptoms. METHODS: From 2009 to 2010, 112 lumbar and 56 cervical spinal disorder patients completed SF-12, Oswestry Disability Index, visual analog pain scale, and Beck Depression Inventory surveys. Multivariate analysis identified predictors of HRQOL, disability, and depressive symptoms. RESULTS: A total of 168 patients completed surveys for this study. The median age of all patients was 60. Nearly 30% of lumbar and 16% of cervical patients were aged 65 or older. Approximately 96% of patients were men. Sixty percent of patients were currently receiving or had pending disability compensation. Nearly 60% of patients were current smokers, approximately 26% reported alcoholism or intravenous drug use, and 26% self reported post-traumatic stress disorder. The most common lumbar spine diagnoses were disk herniation (36.6%) and stenosis (34.8%), and most common cervical spine diagnoses were stenosis (50.0%) and disk herniation (23.2%). Back pain was reported by 93.8% of lumbar patients and leg pain by 83.0%. Neck pain was reported by 96.4% of cervical patients and arm pain by 69.6%. Median SF-12 physical component scores were more than two standard deviations below the US average. Ninety percent of patients had at least moderate physical disability. Sixty-four percent met criteria for depressive symptoms. Visual analog pain score was the strongest predictor of SF-12 physical (beta = -1.32, P < 0.001) and mental (beta = -1.63, P < 0.001) HRQOL and was the prime determinant of depressive symptoms (beta = 1.52, P < 0.001) and disability index score (beta = 4.39, P < 0.0001). Charlson Comorbidity Score and smoking status had no significant impact on HRQOL or disability scores. Age was negatively correlated with depressive symptoms and positively correlated with SF-12 mental component scores. CONCLUSIONS: Spinal disorders have a severe impact on both physical and emotional HRQOL of Veterans and are associated with severe disability and an unusually high prevalence of depressive symptoms. Therapeutic interventions should be targeted to reduce pain, which is a prime determinant of HRQOL, disability, and depressive symptoms. Given high prevalence of multiple risk factors for poor outcomes, studies of spine surgery outcomes in Veterans are needed. PMID- 22311251 TI - Best practices in mixed methods for quality of life research. PMID- 22311252 TI - [Maxillofacial fractures: midface and internal orbit. Part 2: therapeutic options]. AB - While the state of the art of clinical assessment and imaging techniques were described in Part 1, this contribution presents a systematic review of the surgical treatment principles in the management of midface and internal orbit fractures from initial care to definitive treatment, including illustrative case examples. New developments and advances are characterized by limited versus extended surgical approaches, by standardization of osteosynthesis principles with regard to three-dimensional buttress reconstruction, by newly developed individualized implants such as titanium meshes and, especially for complex fracture patterns, by critical assessment of anatomical reconstruction through intraoperative endoscopy, as well as intraoperative and postoperative imaging. Newly developed resorbable soft tissue anchors can be used both for ligament and soft tissue resuspension in order to reduce ptosis effects in the cheeks and nasolabial area to achieve facial aesthetics similar to those prior to the injury. PMID- 22311253 TI - Intermittency in processing explains the diversity and shape of functional grazing responses. AB - Central to theoretical studies of trophic interactions is the formulation of the consumer response to varying food availability. Response functions, however, are only rarely derived in mechanistic ways. As a consequence, the uncertainty in the functional representation of feeding remains large, as, e.g., evident from the ongoing debate on the usage of Ivlev, or Holling type I, II, and III functions in aquatic ecosystem models. Here, I refer to the work of Sjoberg in Ecol Model 10:215-225 (1980) who proposed to apply elements of the queuing theory developed in operational research to plankton-plankton interactions. Within this frame, food item processing is subdivided into two major stages which may operate with variable synchronicity. Asynchronous phasing of the two stages enhances the probability of long total processing times. This phenomenon is here termed feeding intermittency. Intermittency is assumed to determine the functional form of grazing kinetics, for which a novel grazing function containing a "shape" parameter is derived. Using this function, I evaluate the hypotheses that intermittency is influenced by (1) patchiness in the prey field (e.g., related to turbulence), and (2) the ratio of actual prey size to optimal prey size. Evidence for the first hypothesis arises from explaining reported variations in clearance rates of Acartia tonsa under different turbulence regimes. Further model applications to ingestion data for rotifers, copepods, and ciliates support the view that an increasing food size enhances intermittency and, this way, affects functional grazing responses. In the application to ciliate grazing, a possible prey density effect appears, possibly due to an intermittent activation of a feeding sub-stage. Queueing theory offers mechanistic explanations for transitions between Holling I-, II-, and Ivlev-type grazing. In doing so for variable prey size ratios, it may also refine size-based ecosystem models which are increasingly emerging in plankton ecology. PMID- 22311254 TI - Grouping plant species by shared native range, and not by native status, predicts response to an exotic herbivore. AB - Differences among exotic species can be as large as differences between native and exotic species. Typically, however, only the distinction between native and exotic is made when predicting responses in a community. In this paper, I examine the response of plant species to experimental disturbance and exclusion of invasive European rabbits (Oryctolagus cuniculus) in a grassland community with exotic plants originating from five continents. I explore group responses based on native status, shared native range with rabbits, having a congener from the native range of rabbits, life-history (e.g., annual), and life-form (e.g., grass). Individual species responses to rabbits were idiosyncratic, but group responses were predicted by continent of origin, not native status. Native status did predict response to disturbance with almost uniform responses within groups. Exotic species, regardless of origin, were positively affected by disturbance. Native species, in contrast, were negatively affected by disturbance. These results suggest that grouping plant species by native status is valid for questions of disturbance, but when analyzing outcomes of interactions, factors other than native status, such as shared evolutionary history, should be considered. PMID- 22311255 TI - Exotic herbivores on a shared native host: tissue quality after individual, simultaneous, and sequential attack. AB - Plants in nature are often attacked by multiple enemies whose effect on the plant cannot always be predicted based on the outcome of individual attacks. We investigated how two invasive herbivores, the hemlock woolly adelgid (Adelges tsugae) (HWA) and the elongate hemlock scale (Fiorinia externa) (EHS), alter host plant quality (measured as amino acid concentration and composition) when feeding individually or jointly on eastern hemlock (Tsuga canadensis), an important long lived forest tree that is in severe decline. The joint herbivore treatments included both simultaneous and sequential infestations by the two herbivores. We expected resource depletion over time, particularly in response to feeding by HWA. In contrast, HWA dramatically increased the concentration and altered the composition of individual free amino acids. Compared to control trees, HWA increased total amino acid concentration by 330% after 1 year of infestation. Conversely, EHS had a negligible effect when feeding individually. Interestingly, there was a marginally significant HWA * EHS interaction that suggests the potential for EHS presence to reduce the impact of HWA on foliage quality when the two species co-occur. We suggest indirect effects of water stress as a possible physiological mechanism for our results. Understanding how species interactions change the physiology of a shared host is crucial to making more accurate predictions about host mortality and subsequent changes in affected communities and ecosystems, and to help design appropriate management plans. PMID- 22311256 TI - Insect pollination enhances seed yield, quality, and market value in oilseed rape. AB - The relationships between landscape intensification, the abundance and diversity of pollinating insects, and their contributions to crop yield, quality, and market value are poorly studied, despite observed declines in wild and domesticated pollinators. Abundance and species richness of pollinating insects were estimated in ten fields of spring oilseed rape, Brassica napus var. SW StratosTM, located along a gradient of landscape compositions ranging from simple landscapes dominated by arable land to heterogeneous landscapes with extensive cover of semi-natural habitats. In each field, we assessed the contribution of wind and insect pollination to seed yield, seed quality (individual seed weight and oil and chlorophyll contents), and market value in a block experiment with four replicates and two treatments: (1) all flowers were accessible to insects, self and wind pollination, and (2) flowers enclosed in tulle net bags (mesh: 1 * 1 mm) were accessible only to wind and self pollination. Complex landscapes enhanced the overall abundance of wild insects as well as the abundance and species richness of hoverflies. This did not translate to a higher yield, probably due to consistent pollination by honey bees across all fields. However, the pollination experiment showed that insects increased seed weight per plant by 18% and market value by 20%. Seed quality was enhanced by insect pollination, rendering heavier seeds as well as higher oil and lower chlorophyll contents, clearly showing that insect pollination is required to reach high seed yield and quality in oilseed rape. Our study demonstrates considerable and previously underestimated contributions from pollinating insects to both the yield and the market value of oilseed rape. PMID- 22311257 TI - Postoperative delirium: risk factors and management: continuing professional development. AB - PURPOSE: Postoperative delirium often remains undiagnosed and therefore untreated. The purpose of this continuing professional development module is to identify patients at high risk of developing delirium following non-cardiac surgery and to provide tools to aid in the diagnosis of delirium at the bedside. Optimal prevention and treatment strategies are recommended. PRINCIPAL FINDINGS: Delirium is characterized by an acute onset and a fluctuating course, inattention, disorganized thinking and an altered level of consciousness, and occurs in up to 40% of patients in the perioperative period. The pathophysiology of delirium is multifactorial, but it is believed to be related to inflammation, altered neurotransmission, and stress in the patient who has had surgery. Acetylcholine and dopamine appear to play a significant role. There is an increased risk of a poor outcome in patients who develop delirium, including a longer hospital stay and death. Surgical and patient factors play a significant role in predicting who will subsequently develop delirium. Prevention is much more effective than treatment in the management of delirium. The most effective prevention strategies include proactive geriatric assessment and care of the patient on a geriatrics surgical ward as well as prophylactic low-dose antipsychotic agents. From an anesthetic perspective, evidence in some surgical populations would support the use of regional techniques and minimal sedation. If delirium develops, treatment with low-dose oral antipsychotics appears to be most effective. CONCLUSIONS: Delirium is a serious condition that must be recognized early and treated promptly to minimize deleterious outcomes. In order to institute prevention strategies and treat the condition effectively when it occurs, the anesthesiologist must be vigilant in identifying patients at risk and in screening for this condition. PMID- 22311258 TI - Insights into the evolving demographics of anesthesia human resources in Canada. PMID- 22311259 TI - Survival in a large elderly population of patients with dementia and other forms of psychogeriatric diseases. AB - BACKGROUND: Dementia and other psychogeriatric diseases in elderly patients bring an increased risk of death. Better knowledge of prognosis in elderly patients affected by dementia or mental illness should be of great importance in order to improve care plans and assist in medical decisions. METHODS: We have investigated the survival time in 2,112 patients with dementia and other forms of psychogeriatric diseases, enrolled during 1990 to 2005 and followed up until 2009, and the influence of diagnoses, plasma homocysteine level, presence of vascular disease and renal impairment. RESULTS: The survival time after diagnosis in most diagnostic groups is about a third compared to an average population of similar age and sex. Age was the main predictor of survival time in all patients. CONCLUSIONS: All diagnoses, except in patients with subjective cognitive impairments, showed an increased mortality. These estimates can be used for prognosis and planning for patients, carers, service providers and policy makers. PMID- 22311260 TI - Contrast-enhanced MRI of murine myocardial infarction - part II. AB - Mouse models are increasingly used to study the pathophysiology of myocardial infarction in vivo. In this area, MRI has become the gold standard imaging modality, because it combines high spatial and temporal resolution functional imaging with a large variety of methods to generate soft tissue contrast. In addition, (target-specific) MRI contrast agents can be employed to visualize different processes in the cascade of events following myocardial infarction. Here, the MRI sequence has a decisive role in the detection sensitivity of a contrast agent. However, a straightforward translation of clinically available protocols for human cardiac imaging to mice is not feasible, because of the small size of the mouse heart and its extremely high heart rate. This has stimulated intense research in the development of cardiac MRI protocols specifically tuned to the mouse with regard to timing parameters, acquisition strategies, and ECG- and respiratory-triggering methods to find an optimal trade-off between sensitivity, scan time, and image quality. In this review, a detailed analysis is given of the pros and cons of different mouse cardiac MR imaging methodologies and their application in contrast-enhanced MRI of myocardial infarction. PMID- 22311261 TI - Identification and chromosomal localizations of signal transduction genes associated with human ovarian cancer metastasis. AB - Gene chip technology can be used to identify and localize signal transduction genes associated with metastasis. We used the human genome U133A gene chip to detect differences in gene expression profiles among high (H) and low (L) metastatic human ovarian cancer cell lines (HO-8910PM, HO-8910), and normal ovarian tissues (C), to identify metastasis-associated signal transduction genes and determine their chromosomal localizations. A total of 37 signal transduction genes showed more than twofold differences in expression levels between the H and L metastatic ovarian cancer cell lines; of these, 21 genes were up-regulated [signal log ratio (SLR)>=1], and 16 genes were down-regulated (SLR<=-1). Most genes were located on chromosome 1 (7 genes, 18.9%), followed by chromosome 8 (5 genes, 13.5%), then chromosomes 6, 11, and 17 (3 genes each, 8.1%). A total of 21 of the differentially expressed genes (56.7%) were localized on the short arm of the chromosome (q). The disruption of signal transduction gene expression may be an important factor associated with ovarian cancer metastasis. The affected signal transduction genes were localized to chromosomes 1, 8, 6, 11, and 17. PMID- 22311262 TI - Clinicopathologic characteristics and prognosis for molecular subtypes in low grade breast carcinoma: comparison with grade one invasive ductal carcinoma-not otherwise specified. AB - The aim of this study was to investigate the clinicopathologic characteristics and prognosis value for molecular subtypes of low-grade breast carcinoma (LGBC) compared with grade one invasive ductal carcinoma-not otherwise specified (G1-IDC NOS). A retrospective review of 688 LGBC and 1 037 G1-IDC-NOS patients was classified into four different molecular subtypes based on the IHC-based definitions for ER, PR, and c-erbB-2. In LGBC, lymph node metastasis, the percentage of III/IV TNM stages, the expression of Ki-67 and p53 in luminal A subtype were lower than in other subtypes (P<0.01). In addition, the variations of Ki-67 and p53 expression were observed in different subtypes of G1-IDC-NOS (P<0.01). Compared with G1-IDC-NOS, LGBC has higher proportion in the ER positive, PR positive, HER-2 negative, luminal A subtype, Ki-67 negative, and lymph nodes negative group (P<0.01). Furthermore, the overall survival of luminal A and luminal B is higher than triple-negative and HER-2/neu subtype both in LGBC and G1-IDC-NOS in 262 LGBC and 330 G1-IDC-NOS patients with proper follow-up. The classification of molecular subtype together with clinicopathologic factors can significantly improve the traditional prognosticators in predicting outcome for LGBC and G1-IDC-NOS. And it may contribute to guide the treatment for LGBC and G1 IDC-NOS in the future. PMID- 22311263 TI - Aberrant elevated microRNA-146a in dendritic cells (DC) induced by human pancreatic cancer cell line BxPC-3-conditioned medium inhibits DC maturation and activation. AB - It has been shown that the function of dendritic cell (DC) is suppressed in pancreatic cancer patients; however, the detailed mechanism involved in it remains unclear. Here, we used medium conditioned by a highly metastatic human pancreatic cancer cell line BxPC-3 [BxPC-3-conditioned medium (BxCM)] to culture human CD14+ monocyte-derived DCs in vitro. Both DC differentiation and antigen presentation function were inhibited by BxCM. The microRNA-146a (miRNA-146a) expression is aberrantly up-regulated in BxCM-treated DCs. In addition, inhibition of aberrant miRNA-146a expression partly rescues the BxCM-induced defects in differentiation and function of DCs, which may be through regulation of Smad4 expression. Taken together, our findings indicate that aberrant miRNA 146a expression is one of main factors responsible for inhibition of DC maturation and antigen presentation function, and this inhibitory effect on DCs may be due to the repression of Smad4 mediated signal pathway by BxCM. PMID- 22311264 TI - Jun activation domain-binding protein 1 expression in oral squamous cell carcinomas inversely correlates with the cell cycle inhibitor p27. AB - The Jun activation domain-binding protein 1 (Jab1) may be involved in degradation of the cyclin-dependent kinase inhibitor p27, but it has not been clarified. In this study, we observed expression levels of Jab1 and p27 in oral squamous cell carcinoma (OSCC) and normal oral mucosa tissue and evaluated whether the Jab1 expression is correlated with p27 protein levels and how it is clinically relevant OSCC. The clinicopathological features and immunohistochemical expression levels of Jab1 and p27 proteins were immunohistochemically studied in 206 specimens from patients who underwent surgical resection for OSCC. Survival analyses were performed by using the Kaplan-Meier method. Jab1 overexpression was detected in 83% (171 of 206) of OSCCs and 19% (4 of 21) of normal oral mucosa. While p27 expression was 60% in OSCCs. We found an inverse correlation between Jab1 and p27 expression levels (P<0.001). Kaplan-Meier survival analysis showed that Jab1 overexpression and p27 low expression were significantly associated with poor prognosis of patients. Our findings suggest that Jab1 expression is inversely correlated with p27 expression levels, suggesting that Jab1 overexpression contributes to pathogenesis of OSCC by degradating p27 expression. Furthermore, control of Jab1 could be a novel target of therapy in OSCCs. PMID- 22311265 TI - Investigation of serotonin transporter gene (SLC6A4) by child abuse history interaction with body mass index and diabetes mellitus of White female depressed psychiatric inpatients. AB - BACKGROUND: The serotonin transporter gene promoter polymorphism (5HTTLPR) and child abuse have been associated with an increased risk for depression. We previously reported the long/long (l/l) genotype of 5HTTLPR being associated with higher heart rate among patients with a history of child abuse compared with those without a history of child abuse, whereas the short allele carriers did not have heart rate differences dependent on child abuse history. This time, we extended our investigation to other outcomes with body mass index (BMI), and diabetes mellitus (DM) diagnosis. METHODS: A retrospective chart review identified 185 White female depressed inpatients who were genotyped for 5HTTLPR. Child abuse history, BMI, and DM diagnosis were recorded. The relationship between 5HTTLPR, child abuse, and BMI, as well as a prevalence of DM were analyzed. RESULTS: Among the l/l genotype group, patients with a history of child abuse had a higher prevalence of DM (14.3 vs. 0%, P=0.06), and higher BMI (32.3 vs. 27.3 kg/m, P=0.03) compared with those without. Patients with the short allele (s/s or s/l) had fewer differences on the basis of abuse history. CONCLUSION: A potential interaction between 5HTTLPR and child abuse influenced metabolic profiles of White female depressed inpatients. In contrast with the widely recognized 'reactivity' associated with the short allele of 5HTTLPR, our White female depressed psychiatric inpatients with the l/l genotype showed relatively greater clinical pathology in metabolic profiles if they have a history of child abuse than inpatients with at least one short allele who had a history of child abuse. PMID- 22311266 TI - Two new species of Cotingacola Carriker, Phthiraptera: Ischnocera: Philopteridae) from Amazonian Brazil, with comments on host-specificity. AB - This paper describes two new species of Cotingacola Carriker, 1956, C. lutzae n. sp. and C. engeli n. sp., from the cinereous mourner Laniocera hypopyrra (Vieillot) and black-necked red cotinga Phoenicircus nigricollis Swainson (Aves: Passeriformes: Cotingidae), respectively. These species are fully illustrated and compared with their morphologically closest relatives. With the addition of these two new species, this Neotropical chewing louse genus now includes ten species. We also present records from Brazil for two previously described species, C. stotzi Clayton & Price, 1998 and C. parmipapillae Carriker, 1956. The re examination of a specimen identified as 'Cotingacola sp.' in a recent phylogenetic study confirmed that it is C. parmipapillae and that Querula purpurata (Statius Muller) regularly hosts two Cotingacola species, which means that at least three cotingid hosts carry more than one species of Cotingacola. We comment on the variability in the host-specificity of Cotingacola species. PMID- 22311267 TI - Descriptions of digeneans from Sardina pilchardus (Walbaum) (Clupeidae) off the Algerian coast of the western Mediterranean, with a complete list of its helminth parasites. AB - Five species of digeneans parasitic in the pilchard Sardina pilchardus (Walbaum), a little studied host, from off the Algerian coast of the western Mediterranean are redescribed. These are Parahemiurus merus (Linton, 1910) Manter, 1940, Aphanurus stossichii (Monticelli, 1891) Looss, 1907, Aphanurus virgula Looss, 1907, Lecithaster confusus Odhner, 1905 and Pronoprymna ventricosa (Rudolphi, 1819) Poche, 1926. One of these, A. virgula, is a new record for this host. One other digenean, Hemiurus luehei Odhner, 1905, was also recorded from this host. A complete checklist of the helminth parasites of S. pilchardus throughout its distributional range, comprising 104 host-parasite records of 39 taxa, is presented. PMID- 22311268 TI - Description of a second species of Joblingia Dybas & Wenzel, 1947 (Diptera: Streblidae). AB - A new species of Joblingia Dybas & Wenzel, 1947, collected on the bat Myotis ruber (E. Geoffroy) in Southern Brazil, is described, and the type-species, J. schmidti Dybas & Wenzel, 1947, redescribed. The diagnosis of the genus is amended. The external morphology and postgonites of both species are figured. Geographical distribution and host-parasite relationships are discussed. PMID- 22311269 TI - A new genus and species of the Didymozoidae (Digenea) from the skipjack tuna Katsuwonus pelamis (L.) (Scombridae). AB - A new genus and species of didymozoid digenean is described from the skipjack tuna Katsuwonus pelamis (Linnaeus) in the Southwest Atlantic Ocean off Brazil. Pozdnyakovia gibsoni n. g., n. sp. is placed in the Gonapodasmiinae Ishii, 1935. The new genus differs from other genera in the morphology of the posterior regions of the fused pair; this consists of an unlobed, rounded mass fused only dorsally and with a large, elliptical ventral aperture opening into a longitudinal deep cavity from which emerge the two elongate anterior regions. It also differs in the form of the testes, which form two sets of three to four branches in each partner. PMID- 22311270 TI - Descriptions of eight new species of Ligophorus Euzet & Suriano, 1977 (Monogenea: Ancyrocephalidae) from Red Sea mullets. AB - Eight new species of Ligophorus Euzet & Suriano, 1977 (Monogenea: Ancyrocephalidae) are described from two species of mullets from the Red Sea. Ligophorus bykhowskyi n. sp. and L. zhangi n. sp. from Crenimugil crenilabris (Forsskal) differ from other species of the genus in the structure of the male copulatory organ, which has a simple accessory piece and a wide copulatory tube that arises from a large, single-chambered, expanded base. Ligophorus simpliciformis n. sp., L. bipartitus n. sp., L. campanulatus n. sp., L. mamaevi n. sp., L. lebedevi n. sp. and L. surianoae n. sp. from Liza carinata (Valenciennes) are differentiated on the basis of the morphometrics of the hard parts of the haptor and male copulatory organ. The eight species represent the first records of species directly attributed to Ligophorus from the Red Sea. Measurements of the haptoral hard-parts and the male copulatory organ of the new species are analysed with the aid of Principal Component Analysis. Three morphological types of male copulatory organ, five types of anchor, and two types of ventral and three types of dorsal bars were distinguished among these species. L. bykhowskyi and L. zhangi from C. crenilabris have the same type of male copulatory organ and anchors. Those species from Liza carinata have only one common morphological character, a thick copulatory tube, but have two types of accessory piece, four types of anchors and three types of bars. All species of Ligophorus found on mullets in the Red Sea have an accessory piece without a distal bifurcation and thus differ from most species of this genus from other regions of the world's oceans. PMID- 22311272 TI - Cannula-based 25-gauge vitreous tap and injection: a new surgical technique. PMID- 22311271 TI - Further studies on the hypothesis of PARP-1 inhibition as a strategy for lessening the long-term effects produced by perinatal asphyxia: effects of nicotinamide and theophylline on PARP-1 activity in brain and peripheral tissue : nicotinamide and theophylline on PARP-1 activity. AB - Oxygen interruption leads to death when re-oxygenation is not promptly re established. Re-oxygenation triggers a cascade of biochemical events for restoring function at the cost of improper homeostasis. The effects observed long after perinatal asphyxia (PA) have been explained by over-expression of sentinel proteins, such as poly(ADP-ribose) polymerase-1 (PARP-1), competing for NAD(+) during re-oxygenation, leading to the idea that sentinel protein inhibition constitutes a therapeutic strategy. We studied the effects of nicotinamide and theophylline on PARP-1 activity assayed in brain and peripheral (heart) rat tissue 1-24 h after birth, as well as on changes in behaviour and monoamine neurotransmission in adult rats. PA was induced by immersing rat foetuses into a water bath for 0 or 21 min. After resuscitation, the pups were treated with nicotinamide (0.8 mmol/kg, i.p.), theophylline (0.14 mmol/kg, i.p.) or saline (0.9% NaCl) and nurtured by surrogate dams, pending behavioural and microdialysis experiments, or euthanised after birth for assaying PARP-1 activity. To estimate the in vivo distribution of a single dose of nicotinamide or theophylline into brain and peripheral compartment, a series of animals were implanted with microdialysis probes, one into the brain and other subcutaneously, 1 h after birth, assaying the drugs with a HPLC-UV system. Nicotinamide, but not theophylline prevented the long-term effects induced by PA. Only nicotinamide produced a consistent decrease in PARP-1 activity in brain and heart, whether assayed in control or asphyxia-exposed pups. The present results support the idea that the long-term effects induced by PA imply PARP-1 over-activation. PMID- 22311273 TI - A dual-mode single-molecule fluorescence assay for the detection of expanded CGG repeats in Fragile X syndrome. AB - Fragile X syndrome is the leading cause of inherited mental impairment and is associated with expansions of CGG repeats within the FMR1 gene. To detect expanded CGG repeats, we developed a dual-mode single-molecule fluorescence assay that allows acquisition of two parallel, independent measures of repeat number based on (1) the number of Cy3-labeled probes bound to the repeat region and (2) the physical length of the electric field-linearized repeat region, obtained from the relative position of a single Cy5 dye near the end of the repeat region. Using target strands derived from cell-line DNA with defined numbers of CGG repeats, we show that this assay can rapidly and simultaneously measure the repeats of a collection of individual sample strands within a single field of view. With a low occurrence of false positives, the assay differentiated normal CGG repeat lengths (CGG( N ), N = 23) and expanded CGG repeat lengths (CGG( N ), N = 118), representing a premutation disease state. Further, mixtures of these DNAs gave results that correlated with their relative populations. This strategy may be useful for identifying heterozygosity or for screening collections of individuals, and it is readily adaptable for screening other repeat disorders. PMID- 22311274 TI - Construction of an amperometric glucose biosensor based on the immobilization of glucose oxidase onto electrodeposited Pt nanoparticles-chitosan composite film. AB - One-step construction of Pt nanoparticles-chitosan composite film (PtNPs-CS) was firstly proposed as a novel immobilization matrix for the enzymes to fabricate glucose biosensor. This novel interface embedded in situ PtNPs in CS hydrogel was developed by one-step electrochemical deposition in solution containing CS and chloroplatinic acid (H(2)PtCl(6)). Several techniques, including scanning electron microscopy (SEM), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and chronoamperometry were employed to characterize the assembly process and performance of the biosensor. Under the optimized experimental conditions, the resulting biosensor exhibited excellent linear behavior in the concentration range from 1.2 MUM to 4.0 mM for the quantitative analysis of glucose with a limit of detection of 0.4 MUM at a signal-to-noise ratio of 3. The apparent Michaelis-Menten constant (K(M)(app)) was evaluated to be 2.4 mM, showing good affinity. The proposed biosensor offered good amperometric responses to glucose due to the nanostructured sensing film provided plenty of active sites for the immobilization of glucose oxidase (GOD). PMID- 22311275 TI - A dual sensor of fluorescent and colorimetric for the rapid detection of lead. AB - This study demonstrated a simple and reliable method to rapidly detect Pb(2+) in aqueous solution, exploiting gold nanoparticles as a lead ion probe; the results indicated that the dual channels sensor showed high selectivity and sensitivity for Pb(2+) as low as ppm levels in aqueous environment. PMID- 22311276 TI - Contribution of 1H spectroscopy to a brief cognitive-functional test battery for the diagnosis of mild Alzheimer's disease. AB - BACKGROUND/AIMS: The diagnosis of mild or questionable Alzheimer's disease (AD) depends on clinical criteria that often leave a margin for doubt. We aim to verify the diagnostic accuracy of amnestic mild cognitive impairment (aMCI) and AD with proton spectroscopy (1H-MRS) combined with brief cognitive-functional scales. METHODS: The relationship between 1H-MRS of the posterior cingulate cortex and the cognitive performance in Mini Mental State Examination, Blessed Roth Dementia Rating and Functional Assessment Staging of Alzheimer Disease scales were investigated in 25 AD, 10 aMCI and 33 normal control (NC) individuals. RESULTS: The N-acetylaspartate (NAA)/creatine and myoinositol/NAA ratios distinguished AD patients from NC (p<0.005), and added value in diagnostic accuracy and specificity by discriminant function analysis when combined to clinical diagnosis and simple neuropsychiatric scales; an increase of 3.7% (for aMCI patients) and of 5% (for AD individuals) was observed in diagnostic accuracy, and one of 5.5% (aMCI) and of 11.1% (AD) in specificity. CONCLUSION: 1H MRS combined with brief cognitive-functional scales provided maximum diagnostic accuracy of AD patients, and can be useful when subtle cognitive and memory dysfunction is present. PMID- 22311277 TI - NQR parameters of complexes and polarizability effect. AB - The literature data on substituent influence on the nuclear quadrupole resonance frequencies (nu), quadrupole coupling constants (e(2) Qq ? h(- 1) ), and asymmetry parameters (eta) for 36 series of the H-complexes, charge-transfer complexes, transition metal complexes and other donor-acceptor complexes have been considered, using the correlation analysis. Generally the nu, e(2) Qq ? h(- 1) , and eta values were first established to depend on the inductive, resonance, polarizability, and steric effects of substituents. The presence or otherwise of certain effects as well as relation between their contributions are determined by the type of series. The polarizability effect owes its existence to the appearance of an excess charge on the indicator centre as a result of the complexation. The contribution of this effect ranges up to 75%. PMID- 22311278 TI - Manipulation of cortical gray matter oxygenation by hyperoxic respiratory challenge: field dependence of R(2) * and MR signal response. AB - The aim of this study was to quantitatively assess the field strength dependence of the transverse relaxation rate (R(2) *) change in cortical gray matter induced by hyperoxia and hyperoxic hypercapnia versus normoxia in an intra-individual comparison of young healthy volunteers. Medical air (21% O(2) ), pure oxygen and carbogen (95% O(2) , 5% CO(2) ) were alternatively administered in a block-design temporal pattern to induce normoxia, hyperoxia and hyperoxic hypercapnia, respectively. Local R(2) * values were determined from three-dimensional, multiple, radiofrequency-spoiled, fast field echo data acquired at 1.5, 3 and 7 T. Image quality was good at all field strengths. Under normoxia, the mean gray matter R(2) * values were 13.3 +/- 2.7 s(-1) (1.5 T), 16.9 +/- 0.9 s(-1) (3 T) and 29.0 +/- 2.6 s(-1) (7 T). Both hyperoxic gases induced relaxation rate decreases DeltaR(2) *, whose magnitudes increased quadratically with the field strength [carbogen: -0.69 +/- 0.20 s(-1) (1.5 T), -1.49 +/- 0.49 s(-1) (3 T), 5.64 +/- 0.67 s(-1) (7 T); oxygen: -0.39 +/- 0.20 s(-1) (1.5 T), -0.78 +/- 0.48 s(-1) (3 T), -3.86 +/- 1.00 s(-1) (7 T)]. Carbogen produced larger R(2) * changes than oxygen at all field strengths. The relative change DeltaR(2) */R(2) * also increased with the field strength with a power between 1 and 2 for both carbogen and oxygen. The statistical significance of the R(2) * response improved with increasing B(0) and was higher for carbogen than for oxygen. For a sequence with pure T(2) * weighting of the signal response to respiratory challenge, the results suggested a maximum carbogen-induced signal difference of 19.3% of the baseline signal at 7 T and TE = 38 ms, but a maximum oxygen-induced signal difference of only 3.0% at 1.5 T and TE = 76 ms. For 3 T, maximum signal changes of 4.7% (oxygen) and 8.9% (carbogen) were computed. In conclusion, the R(2) * response to hyperoxic respiratory challenge was stronger for carbogen than for oxygen, and increased quadratically with the static magnetic field strength for both challenges, which highlights the importance of high field strengths for future studies aimed at probing oxygen physiology in clinical settings. PMID- 22311279 TI - Variation in concentrations of high-molecular-weight glutenin subunits and macropolymers in wheat grains of a recombinant inbred lines population and in two contrasting eco-sites in China. AB - BACKGROUND: Concentrations of high-molecular-weight glutenin subunits and macropolymers in wheat grains are important indicators of grain quality, which are genetically determined and affected by environmental factors. The 6 VS.6AL translocation chromosome segment is reported to own high powdery mildew and yellow rust resistance genes of Pm21 and Yr26. This study investigated the variation in concentrations of high-molecular-weight glutenin subunits (HMW-GS) and glutenin macropolymer (GMP) in response to the 6 VS.6AL translocation segment and the two contrasting sites. RESULTS: Large variations in concentrations of HMW GS and GMP were observed within lines containing different HMW-GS compositions and between the contrasting eco-sites. However, 6 VS.6AL chromosome translocation segment showed no significant effects on concentrations of HMW-GS and GMP. In addition, HMW-GS concentration was also found to be significantly correlated with the GMP concentration. CONCLUSION: Concentrations of HMW-GS and GMP are largely affected by the eco-sites and the composition of HMW-GS, whilst not by the presence of 6 VS.6AL chromosome segment translocation. The 6 VS.6AL translocation is suggested as potential donor for breeding wheat cultivars for high resistence to powdery mildew and yellow rust with less risk of undesirable effects on grain quality. PMID- 22311280 TI - Autonomic nervous system function in rheumatoid arthritis. AB - The sympathoneural and the adrenomedullary systems are involved in regulation of immune processes. Their impairment has been suggested in patients with rheumatoid arthritis (RA). In this study, sympathetic response to orthostasis was evaluated in 22 RA females with <40 years of age and in 15 matched healthy controls. The testing consisted of stabilization period in supine position, legs-up position, 10 min of orthostasis and again supine position. In each of the body position blood samples were drawn, blood pressure and electrocardiogram was recorded. Plasma levels of epinephrine (EPI) and norepinephrine (NE) were measured and sympathoneural activity was evaluated by analysis of heart rate variability (HRV). During the testing, RA patients had similar EPI and NE concentrations compared to controls. Baseline diastolic blood pressure tended to be higher in RA patients compared to controls; however, blood pressure response to orthostasis was comparable between the groups. The RA and control groups did not differ in heart rate and HRV parameters. This study showed normal reactivity of the sympathoneural and the adrenomedullary systems during orthostatic challenge in RA patients younger than 40 years. PMID- 22311281 TI - Counterclockwise rotation of Roux-en-Y limb significantly reduces internal herniation in laparoscopic Roux-en-Y gastric bypass (LRYGB). AB - INTRODUCTION: Internal hernias continue to be a significant source of morbidity after LRYGB. Literature addressing the technique of Roux limb construction as a predisposing factor is sparse. The objective of this study is to evaluate the impact of Roux limb construction technique on the development of internal hernias. METHODS: In this study, we included 444 (367 (82.7%) were females and 77 (17.3%) were males, two deaths excluded from the analysis) consecutive patients from our institutional bariatric database who underwent LRYGB. Variables collected include demographics, body mass index (BMI) before and after the procedure, and postoperative small bowel obstruction secondary to internal herniation. Technical details collected include: type of Roux-en-Y limb construction, Peterson's defect closure at initial operation, and reoperative findings. Roux limbs were constructed in 291 patients by a clockwise rotation of the bowel and jejunojejunostomy performed on the right side of the axis of the mesentery (group 1). In 151 patients, the Roux limb was constructed by a counterclockwise rotation of the Roux limb resulting in the jejunojejunostomy on the left side of the axis of the mesentery (group 2). We also analyzed the impact of Peterson's space closure on internal hernias. Fisher's exact test and Chi square test were used for the analysis. RESULTS: Of a total 442 (mean age, 43.7 +/- 10.3 years; mean BMI pre-op was 46.4 +/- 5.1; and BMI after median follow-up of 12 months was 34.5 +/- 6.98) patients included in the study, 21 (4.7%) internal hernias were identified. Of 21 internal hernias, 17 (81%) were through Peterson's space and four (19%) were through the mesenteric defect. Group 1 patients had significantly higher overall internal hernias (20/291, 6.9% vs. 1/151, 0.7%; P = 0.0018) and Peterson's hernias (16/291, 5.5% vs. 1/151, 0.7%; P = 0.0089) compared with group 2. In addition, no significant difference was noted in the incidence of Peterson's hernia whether the defect was closed or not closed (closed group, 4/117 and 3.4% vs. not closed, 13/325, 4%; P = 1.00). Within the group where Peterson's defect was closed, clockwise rotation and anastomosis on the right side of the axis of the mesentery was associated with significantly higher incidence of Peterson's hernias compared with counterclockwise rotation (4/54 vs. 0/63; P = 0.043). In the group where Peterson's defect was not closed, clockwise rotation was associated with higher incidence of internal hernias that did not reach statistical significance (12/237, 5.1% vs. 1/88, 1.1%; P = 0.12). This study demonstrates that the technique for construction of the Roux limb is a major factor in the development of internal hernias. Construction of the Roux limb with a counterclockwise rotation of the bowel, such that both jejunojejunostomy anastomosis and ligament of Treitz are to the left of the axis of the mesentery significantly reduces the incidence of internal hernias. PMID- 22311282 TI - Early mortality risk score: identification of poor outcomes following upfront surgery for resectable pancreatic cancer. AB - BACKGROUND: Identifying pancreatic cancer patients at high risk of early mortality following pancreaticoduodenectomy (PD) is important for treatment decisions in a multidisciplinary setting. This study examines the preoperative predictors of early mortality following PD and combines these variables into an early mortality risk score (EMRS). METHODS: Medical records of patients who underwent PD for pancreatic adenocarcinoma at the Johns Hopkins Hospital between 30 August 1993 and 28 February 2005 were reviewed. Cox proportional hazards analysis was performed to identify predictors of early mortality, defined as death at 9 and 12 months. EMRS was constructed from univariate associated risk factors (age >75 years, tumor size >= 3 cm, poor differentiation, co-morbid diseases) with each factor assigned 1 point (range of 0-4). EMRS was evaluated as an independent predictor of death at 9 and 12 months. RESULTS: On univariate analysis, risk factors for death at 9 months included age >= 75 years (RR, 1.6; p = .009), comorbid disease (RR, 1.5; p = 0.020), tumor >= 3 cm (RR, 1.4; P = 0.050), and poor differentiation (RR, 2.1; P < 0.001). EMRS was associated with early mortality among those who did (p = 0.038) and did not receive adjuvant treatment (p < 0.001). A modified EMRS without tumor differentiation was also associated with early mortality (p < 0.001). Results persisted when reanalyzed using death at 12 months. CONCLUSIONS: EMRS may identify patients at risk of early mortality following PD who may be candidates for alternatively sequenced treatment protocols. Prospective validation of this EMRS is needed. PMID- 22311283 TI - Effects of RS9939609 gene variant in FTO gene on weight loss and cardiovascular risk factors after biliopancreatic diversion surgery. AB - BACKGROUND: The high variation in responses to bariatric surgery might be partially explained by genetic effects. Recently, common polymorphisms of the fat mass and obesity-associated gene (FTO) have been linked to obesity in some populations. Only two studies have investigated the effect of FTO variants on weight loss of morbid obese patients undergoing bariatric surgery with contradictory results. OBJECTIVE: We decided to investigate the role of the rs9939609 FTO gene polymorphism on outcomes after a biliopancreatic diversion surgery (BPD) in morbidly obese patients. DESIGN: A sample of 119 morbidly obese patients' body mass index (BMI) > 40 kg/m(2) were operated. Weight, fat mass, blood pressure, basal glucose, triacylglycerols, total cholesterol, low density lipoprotein cholesterol and high density lipoprotein cholesterol were measured at basal visit and at each visit (basal, 3, 9 and 12 months). The frequency of metabolic comorbidities was recorded at each visit. RESULTS: Thirty-seven patients (31.1%) had genotype TT (wild type group), 58 (48.7%) patients had genotype TA and 24 patients (20.2%) had genotype AA. In the wild and mutant type groups, BMI, weight, waist circumference, systolic blood pressure and diastolic blood pressure decreased in a significant way. In the wild type groups, glucose, total cholesterol, low density lipoprotein (LDL) cholesterol and triacylglycerol concentrations decreased at 3, 9 and 12 months after surgery. In the mutant type groups, glucose, total cholesterol and triacylglycerol concentrations decreased at 3, 9 and 12 months after surgery. LDL cholesterol decreased at 9 and 12 months after surgery. Initial weight percent loss at 3 months of follow-up was higher in the wild type group (26.1% vs. 18.6%: p < 0.05). The initial weight percent loss at 9 or 12 months was similar in both genotypes. CONCLUSION: Our study showed a higher initial weight loss at 3 months after the TT variant of FTO gene (rs9939609). However, the weight loss at 9 and 12 months of BPD was similar in both genotypes with a significant improvement in biochemical parameters and cardiovascular comorbidities. PMID- 22311284 TI - What is the optimal treatment for peripancreatic fluid collections? PMID- 22311285 TI - Shoulder injury in the overhead athlete. PMID- 22311286 TI - Anatomic and biomechanical fundamentals of the thrower shoulder. AB - The act of throwing requires proper functioning and timing of the entire kinetic chain musculature to generate a coordinated movement pattern for ball delivery. The role of the shoulder complex is vital in the transmission of force from the lower extremities and trunk to the arm and hand. A review of the anatomic and biomechanical factors of the shoulder girdle will be discussed as it pertains to the thrower. An understanding of the relationship of the muscles, ligaments, and osseous structures is essential to the successful diagnosis and treatment of shoulder pathology and dysfunction. PMID- 22311287 TI - Physical examination of the overhead athlete's shoulder. AB - Overhead athletes seek the services of an orthopedic surgeon because of pain and/or dysfunction. It is important to address the cause of the symptoms more so than the source of the patient's pain, so that treatment will eliminate the problem rather than merely ameliorate symptoms temporarily. In order to accomplish a thorough assessment of shoulder function, the examiner must expand his/her view from isolated assessment of the glenohumeral joint range of motion, stability, assessment of rotator cuff strength, palpation and provocative maneuvers, and add assessment of the shoulder in the context of the kinetic chain. The examination of the thrower's shoulder, coupled with a thorough history, will usually provide a solid functional diagnosis and provide a good idea as to the presence of structural damage. As a result, the value of rehabilitation and the benefit of surgical intervention are made more predictable. PMID- 22311288 TI - Kinetic chain abnormalities in the athletic shoulder. AB - Overhead activities require the shoulder to be exposed to and sustain repetitive loads. The segmental activation of the body's links, known as the kinetic chain, allows this to occur effectively. Proper muscle activation is achieved through generation of energy from the central segment or core, which then transfers the energy to the terminal links of the shoulder, elbow, and hand. The kinetic chain is best characterized by 3 components: optimized anatomy, reproducible efficient motor patterns, and the sequential generation of forces. However, tissue injury and anatomic deficits such as weakness and/or tightness in the leg, pelvic core, or scapular musculature can lead to overuse shoulder injuries. These injuries can be prevented and maladaptations can be detected with a thorough understanding of biomechanics of the kinetic chain as it relates to overhead activity. PMID- 22311289 TI - Pathomechanics of the throwing shoulder. AB - Many anatomic, physiological, and biomechanical alterations have been observed in overhead athletes who present with painful shoulders. This is probably due to the complex kinetic chain mechanics required in the overhead throwing or serving motion. Any alteration along the kinetic chain can result in deficits in force production or increase in joint loads in other parts of the chain. The "disabled throwing shoulder" (DTS) is a general term that describes the limitations in function that exist in symptomatic overhead athletes. DTS typically results from a "cascade to injury" with alterations in the kinetic chain. Evaluation of athletes with the DTS should include examination of the local and distant anatomic injuries and screening for physiological (muscle inflexibilities, weakness, or imbalances) or biomechanical (motions, positions) alterations. PMID- 22311290 TI - Internal impingement: concurrent superior labral and rotator cuff injuries. AB - Internal impingement is a general term usually applied to the pathologic combination of a superior labral anterior-posterior injury and a partial thickness rotator cuff injury that is commonly seen in the disabled throwing shoulder. Clinical presentation varies but involves a combination of internal derangement (popping, clicking, catching, sliding) and rotator cuff weakness. Evaluation should be precise to delineate all components of the injury. Treatment must be directed toward both of the components and any other coexisting pathology. Labral repair should aim at restoring all aspects of the roles of the labrum. Rotator cuff treatment should take into account the need for optimal rotation and may not include complete take down and repair. Pitfalls in diagnosing and treating internal impingement should be known and avoided. Comprehensive rehabilitation emphasizing kinetic chain principles and full ranges of motion should be used. PMID- 22311291 TI - Glenohumeral internal rotation deficit: pathogenesis and response to acute throwing. AB - Overhand throwing places high loads and stresses on the joints and tissues of the shoulder and arm. As a result, throwing athletes regularly demonstrate altered shoulder internal and external ranges of motion where internal rotation (IR) is decreased and external rotation is increased in the dominant arm when compared with the nondominant arm. This alteration can exist as a result of alterations to the bones (humeral retroversion), capsule (posterior thickening), or muscle (passive stiffness known as thixotropy). When the amount of IR or total arc of motion difference reaches a certain threshold (typically 20 or more degrees of IR or 8 degrees total arc difference), it is known as glenohumeral internal rotation deficit or total arc of motion deficit. Glenohumeral internal rotation deficit and total arc of motion deficit can cause alterations in biomechanics such as scapular "wind-up" or alteration of glenohumeral joint kinematics, which can in turn lead to clinical findings of impingement and labral pathology. This study will review the causes of motion alteration, effects of altered motion on the throwing motion, provide definitions for the various types of rotation deficits, and how to evaluate and treat rotational deficits. PMID- 22311292 TI - Evaluation and management of scapular dysfunction. AB - The scapula plays an important role in shoulder function and requires both significant mobility and stability. Normal motion is 3-dimensional, and during arm elevation consists of upward rotation, posterior tilting, and external rotation as well as clavicular elevation and retraction. Examination should include visual observation, symptom alterations tests, testing of muscle strength, and flexibility of key structures including the pectoralis minor, posterior shoulder and thoracic spine. Treatment consists of graded resistive exercise, neuromuscular retraining, stretching, manual therapy, and taping where necessary. Although several studies suggest a relationship between abnormal scapular motion and symptoms, strong evidence directly supporting a causal relationship is lacking and further work is necessary to clarify this relationship. PMID- 22311293 TI - Rehabilitation after surgical management of the thrower's shoulder. AB - The overhead throwing motion is a complex and coordinated movement pattern involving the lower extremities, the trunk, and the upper extremity. Because of these tremendous demands on the shoulder, various shoulder injuries may occur. Two of the more common injuries to throwers are shoulder instability and superior labrum anterior-posterior lesions. Although nonoperative treatment is frequently successful in treating these conditions, surgical management may be necessary for the athlete to return to their sport. The purpose of this article is to review the first 3 phases of rehabilitation after arthroscopic capsular stabilization and superior labrum anterior-posterior debridement or repair. The fourth phase, return to throwing, will be covered in the final section. PMID- 22311294 TI - Urinary 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin-F1alpha in healthy post-menopausal and pre-menopausal women receiving aspirin 100 mg. AB - The prevalence of cardiovascular diseases in women increases sharply after menopause. In postmenopausal women, thromboxane production increases while prostacyclin decreases. Low dose aspirin reduces the production of both thromboxane and prostacyclin. The present study was an open-label clinical trial with two parallel groups of 15 premenopausal women and 15 postmenopausal women. Twenty-four hours urine was collected from each subject before and after aspirin 100 mg daily for 7 days. The concentration of thromboxane and prostacyclin was measured as their metabolites (11-dehydro-thromboxane B(2) and 2,3-dinor-6-keto prostaglandin-F(1alpha)) in urine using enzyme immunoassay methods. This study showed that aspirin significantly reduced thromboxane in both groups with significantly larger percentage reduction in postmenopausal women compared to premenopausal women (73.32 vs. 61.13%, p = 0.021). This study also showed that aspirin reduced prostacyclin significantly in both groups, but the percentage reduction between the groups was not significantly different. The decrease in the ratio of 11-dTXB(2)/2,3-dinor-6-keto-PGF(1alpha) should be compared to assess aspirin efficacy as an antithrombotic. Calculation of the ratio of 11-dTXB(2)/2,3 dinor-6-keto-PGF(1alpha) before aspirin consumption was higher in postmenopausal women than in premenopausal women. The decrease in 11-dTXB(2)/2,3-dinor-6-keto PGF(1alpha) ratio by aspirin was greater in postmenopausal women than in premenopausal women (1.91 vs. 0.17; p = 0.022). It was concluded that aspirin reduced thromboxane and prostacyclin significantly in each group with significant 11-dTXB(2) percentage reduction between groups and non-significant 2,3-dinor-6 keto-PGF(1alpha) percentage reduction between groups, but reduced the 11 dTXB(2)/2,3-dinor-6-keto-PGF(1alpha) ratio much larger in postmenopausal women compared to that in premenopausal women. PMID- 22311295 TI - Professor B S Ramakrishna--President, Indian Society of Gastroenterology 2011 2012. PMID- 22311297 TI - Facial amphipathic deoxycholic acid-modified polyethyleneimine for efficient MMP 2 siRNA delivery in vascular smooth muscle cells. AB - Clinical applications of RNA interference-based therapeutics such as small interfering RNAs (siRNAs) have been limited mainly due to low intracellular delivery efficiency in vitro and in vivo. In this study, facially amphipathic deoxycholic acid (DA)-modified polyethyleneimine (PEI(1.8)) (DA-PEI(1.8)) was synthesized and used as a potent carrier system for siRNA targeted against matrix metalloproteinase-2 (MMP-2) to inhibit the migration of vascular smooth muscle cells (SMCs), which is the major pathomechanism in the development of atherosclerosis and restenosis after arterial injury. A representative facial amphipathic bile acid DA having a high membrane permeability was conjugated to the terminal amine groups of the low molecular weight PEI(1.8) via amide bonds. The DA-PEI(1.8) conjugates formed self-assembled nanoparticles with siRNA molecules in an aqueous phase and the DA-PEI(1.8)/siRNA polyplexes became stabilized and condensed as particle incubation time increased from 0 to 4h. Both cellular internalization and target gene silencing were enhanced as the DA PEI(1.8)/siRNA polyplexes stabilized. When vascular SMCs were transfected with MMP-2 siRNA, the DA-PEI(1.8)/siRNA polyplex formulation led to a significant decrease in MMP-2 gene expression, resulting in the suppression of cell migration. These results suggest that the DA-PEI(1.8)/MMP-2 siRNA delivery system may be useful in anti-restenotic treatment for various vasculoproliferative disorders such as atherosclerosis, in-stent restenosis, and vein graft failure. PMID- 22311296 TI - Giardiasis: a review on assemblage distribution and epidemiology in India. AB - Giardiasis is a significant cause of diarrheal disease and associated morbidity in children and adults worldwide. In addition to diarrhea, it can also lead to malnutrition and cognitive deficits in children from developing countries. Giardia duodenalis is considered to be a species complex of several assemblages, of which assemblage A and B are predominantly associated with human infections. Assemblage type has been associated with risk of occurrence of symptoms and duration of illness. Hence genotyping of giardial isolates may help understand better the epidemiology and transmission ecology of the disease in a particular setting or area. In India, prevalence rates of Giardia infection in patients with diarrhea range from 0.4% to 70%, and asymptomatic cyst passage has been found to be as high as 50% in rural southern India. In this review, the global distribution of giardial assemblage, zoonotic transmission and the association of assemblage with disease have been discussed, followed by epidemiology of giardiasis in India. PMID- 22311298 TI - Effective down-regulation of breast cancer resistance protein (BCRP) by siRNA delivery using lipid-substituted aliphatic polymers. AB - Breast Cancer Resistance Protein (BCRP, ABCG2) is an efflux protein whose aberrant activity has been linked to multidrug resistance in cancer. Although siRNA delivery to down-regulate BCRP expression is promising to sensitize tumor cells against drugs, therapeutic use of siRNA requires effective carriers that can deliver siRNA intracellularly with minimal toxicity on target cells. This study explored the feasibility of special class of cationic polymers, namely lipid-substituted low molecular weight (2kDa) polyethyleneimine (PEI), as a carrier for siRNA-mediated BCRP down-regulation. Structure-function studies methodically evaluated the effect of a range of lipophilic substitutions for siRNA delivery and BCRP down-regulation. Our results showed a significant increase in siRNA delivery as a function of lipid substitution for a range of lipids ranging from C8 to C18. The BCRP silencing was correlated to siRNA delivery efficiency of the polymers, and effectively lasted for ~5days after a single treatment of siRNA. BCRP down-regulation sensitized the drug-resistant cells to cytotoxic effect of mitoxantrone by a ~14-fold decrease in the IC(50) value, whose effect was evident even after 14days. This study demonstrated the possibility of functional siRNA delivery by lipid-modified low molecular weight PEI and highlighted the importance of the extent and nature of lipid substitution in effective siRNA delivery. PMID- 22311299 TI - Glucagon-like peptide 1 (GLP-1) can reverse AMP-activated protein kinase (AMPK) and S6 kinase (P70S6K) activities induced by fluctuations in glucose levels in hypothalamic areas involved in feeding behaviour. AB - The anorexigenic peptide, glucagon-like peptide-1 (GLP-1), reduces glucose metabolism in the human hypothalamus and brain stem. The brain activity of metabolic sensors such as AMP-activated protein kinase (AMPK) responds to changes in glucose levels. The mammalian target of rapamycin (mTOR) and its downstream target, p70S6 kinase (p70S6K), integrate nutrient and hormonal signals. The hypothalamic mTOR/p70S6K pathway has been implicated in the control of feeding and the regulation of energy balances. Therefore, we investigated the coordinated effects of glucose and GLP-1 on the expression and activity of AMPK and p70S6K in the areas involved in the control of feeding. The effect of GLP-1 on the expression and activities of AMPK and p70S6K was studied in hypothalamic slice explants exposed to low- and high-glucose concentrations by quantitative real time RT-PCR and by the quantification of active-phosphorylated protein levels by immunoblot. In vivo, the effects of exendin-4 on hypothalamic AMPK and p70S6K activation were analysed in male obese Zucker and lean controls 1 h after exendin 4 injection to rats fasted for 48 h or after re-feeding for 2-4 h. High-glucose levels decreased the expression of Ampk in the lateral hypothalamus and treatment with GLP-1 reversed this effect. GLP-1 treatment inhibited the activities of AMPK and p70S6K when the activation of these protein kinases was maximum in both the ventromedial and lateral hypothalamic areas. Furthermore, in vivo s.c. administration of exendin-4 modulated AMPK and p70S6K activities in those areas, in both fasted and re-fed obese Zucker and lean control rats. PMID- 22311300 TI - Comparison of long-term prognosis of laparoscopy-assisted gastrectomy and conventional open gastrectomy with special reference to D2 lymph node dissection. AB - BACKGROUND: Laparoscopy-assisted gastrectomy (LAG) is becoming widely used for early gastric cancer. However, how the curability and long-term prognosis of LAG and open gastrectomy (OG) for early and advanced gastric cancer compare remains unclear. This study assessed short- and long-term outcomes after LAG with lymph node dissection in early and advanced gastric cancer. METHODS: A total of 332 patients who underwent LAG or OG for early and advanced gastric cancer from January 2001 through December 2010 were reviewed retrospectively. The mean operating time, estimated mean blood loss, number of dissected lymph nodes, and survival rates were compared between LAG and OG for early and advanced gastric cancer. RESULTS: Overall, 47.6% (158/332) of patients underwent LAG; D1, D1+ lymph node dissection was carried out in 77.2%, with D2 dissection in 22.8%. Only one patient required conversion to OG. Comparing LAG and OG with D1, D1+ lymph node dissection for early gastric cancer (EGC), mean operating time was significantly longer, estimated mean blood loss was significantly smaller, and the average number of retrieved lymph nodes was significantly greater with LAG. The rate of specific postoperative morbidity was 17.2% for LAG patients and 25.0% for OG patients, with no postoperative mortality. Survival and recurrence rates were not significantly different. Comparing LAG and OG with D2 lymph node dissection for advanced gastric cancer (AGC), mean operating time was significantly longer and estimated mean blood loss was significantly smaller with LAG, while the average number of retrieved lymph nodes, specific postoperative morbidity and mortality, and survival and recurrence rates were not significantly different. CONCLUSIONS: LAG with D1, D1+ lymph node dissection for EGC is safe and equivalent to open gastrectomy in curability. Moreover, LAG with D2 lymph node dissection for AGC is comparable to OG with D2 lymph node dissection with regard to short- and long-term results. PMID- 22311301 TI - Robotic liver resection: technique and results of 30 consecutive procedures. AB - BACKGROUND: Robotic surgery can enhance a surgeon's laparoscopic skills through a magnified three-dimensional view and instruments with seven degrees of freedom compared to conventional laparoscopy. METHODS: This study reviewed a single surgeon's experience of robotic liver resections in 30 consecutive patients, focusing on major hepatectomy. Clinicopathological characteristics and perioperative and short-term outcomes were analyzed. RESULTS: The mean age of the patients was 52.4 years and 14 were male. There were 21 malignant tumors and 9 benign lesions. There were 6 right hepatectomies, 14 left hepatectomies, 4 left lateral sectionectomies, 2 segmentectomies, and 4 wedge resections. The average operating time for the right and left hepatectomies was 724 min (range 648-812) and 518 min (range 315-763), respectively. The average estimated blood loss in the right and left hepatectomies was 629 ml (range 100-1500) and 328 ml (range 150-900), respectively. Four patients (14.8%) received perioperative transfusion. There were two conversions to open surgery (one right hepatectomy and one left hepatectomy). The overall complication rate was 43.3% (grade I, 5; grade II, 2; grade III, 6; grade IV, 0) and 40% in 20 patients who underwent major hepatectomy. Among the six (20.0%) grade III complications, a liver resection related complication (bile leakage) occurred in two patients. The mean length of hospital stay was 11.7 days (range 5-46). There was no recurrence in the 13 patients with hepatocellular carcinoma during the median follow-up of 11 months (range 5-29). CONCLUSIONS: From our experience, robotic liver resection seems to be a feasible and safe procedure, even for major hepatectomy. Robotic surgery can be considered a new advanced option for minimally invasive liver surgery. PMID- 22311302 TI - Robotic transaxillary endocrine surgery: a comparison with conventional open technique. AB - BACKGROUND: Robotic transaxillary (RT) endocrine surgery may improve cosmetic outcomes. We report our initial experience in RT thyroid and parathyroid surgery and the associated learning curve, and compare early surgical outcomes to those of open thyroidectomy (OT) and focal parathyroidectomy (FP). METHODS: A prospective database review identified patients who had undergone RT endocrine surgery. A case-matched group who underwent OT or FP was also identified. Demographics, histopathology, operative outcomes, and follow-up data were collected. Groups were compared using Student's t test and the chi(2) test. RESULTS: Fifteen RT procedures were performed: 11 RT thyroidectomies (6 total, 5 lobectomies) and 4 RT parathyroidectomies (2 focal, 2 unilateral), representing 5.9% and 2.2% of thyroidectomies and parathyroidectomies performed. The OT group contained 16 patients (13 totals, 3 lobectomies). The FP group contained 12 patients. There was no significant difference in age, gender, BMI, pathology, or complications between the groups. Mean operating time was significantly longer in the RT group (232 vs. 109 min, P = 0.0002) as was mean incision length (6 vs. 3.6 cm, P < 0.0001). No RT procedures were converted and no major complications occurred. Operating time decreased significantly over consecutive cases demonstrating a learning curve. CONCLUSIONS: RT thyroidectomy and parathyroidectomy can be performed safely by specialist endocrine surgeons, early in their learning curve, without an increased complication rate, albeit with significantly longer operating times. PMID- 22311303 TI - Minimally invasive liver surgery for metastases from colorectal cancer: oncologic outcome and prognostic factors. AB - BACKGROUND: Few reports exist on long-term survival after minimally invasive liver surgery (MILS) for colorectal liver metastases (CRLM). No data are available assessing prognostic factors in the era of current modern treatment strategies. METHODS: Between October 2002 and December 2008, 274 consecutive patients were analyzed on an intention-to-treat basis. Open liver surgery (OLS) was performed in 193 patients for a total of 437 metastases, and MILS was performed in 81 patients for 176 metastases. Systemic chemotherapy was administered preoperatively in 173 and postoperatively in 174 patients. The impact of 23 potential prognostic factors on disease-free (DFS) and overall survival (OS) was evaluated using univariable and multivariable Cox regression models. RESULTS: Postoperative complications were observed in 54 patients after OLS and in 11 after MILS (p = 0.016). The median postoperative length of hospital stay was 9 days after OLS and 5 days after MILS (p < 0.0001). For the entire patient population, the 5 year DFS and OS rates were 29.9 and 59.5%, respectively. No differences in survival between patients treated with MILS and OLS were observed (p = 0.63). In univariable analyses, the number of liver metastases and the overall Fong's clinical risk score (CRS) were the only two variables that predicted DFS (p <= 0.0035) and OS (p <= 0.0005). In multivariable analyses, the total CRS was the only independent predictor of both DFS (p = 0.0002) and OS (p = 0.002). CONCLUSION: The long-term oncologic outcome of surgically treated patients with CRLM is determined by the Fong's CRS. Although MILS does not influence long-term survival, it has a beneficial impact on the immediate postoperative clinical outcome. PMID- 22311304 TI - Lightweight versus heavyweight mesh in laparoscopic inguinal hernia repair: a meta-analysis. AB - BACKGROUND: Reinforcement of inguinal hernia repair with prosthetic mesh is standard practice but can cause considerable pain and stiffness around the groin and affect physical functioning. This has led to various types of mesh being engineered, with a growing interest in lighter-weight mesh. Minimally invasive approaches have also significantly reduced postoperative recovery from inguinal hernia repair. The aim of this systematic review was to compare the outcomes after laparoscopic inguinal repair using new lightweight or traditional heavyweight mesh in published randomised controlled trials. METHODS: Medline, Embase, trial registries, conference proceedings, and reference lists were searched for controlled trials of heavyweight versus lightweight mesh for laparoscopic repair of inguinal hernias. The primary outcomes were recurrence and chronic pain. Secondary outcomes were visual analogue pain score at 7 days postoperatively, seroma formation, and time to return to work. Risk differences were calculated for categorical outcomes and standardised mean differences for continuous outcomes. RESULTS: Eight trials were included in the analysis of 1,667 hernias in 1,592 patients. Mean study follow-up was between 2 and 60 months. There was no effect on recurrence [pooled analysis risk difference 0.00 (95% CI 0.01 to 0.01), p = 0.86] or chronic pain [pooled analysis risk difference -0.02 (95% CI -0.04 to 0.00); p = 0.1]. Lightweight and heavyweight mesh repair had similar outcomes with regard to postoperative pain, seroma development, and time to return to work. CONCLUSION: Both mesh options appear to result in similar long and short-term postoperative outcomes. Further long-term analysis may guide surgeon selection of mesh weight for laparoscopic inguinal hernia repair. PMID- 22311305 TI - Item response theory reveals variability of functional impairment within clinical dementia rating scale stages. AB - BACKGROUND/AIMS: To investigate whether an item response theory (IRT) approach to measuring variations of dementia severity within Clinical Dementia Rating (CDR) stages is associated with activities of daily living (ADLs). METHODS: IRT estimates of dementia severity within CDR stages in 1,181 patients were correlated with ADLs and analyzed. RESULTS: IRT-determined dementia severity was significantly correlated with ADLs in three of four impaired dementia stages. CONCLUSION: An IRT approach shows considerable advantages over traditional scoring practices of the CDR not only because it increases precision in dementia measurement, but also because it enables one to discover more precise associations with functional outcomes such as ADLs. PMID- 22311306 TI - Toward human resource management in inter-professional health practice: linking organizational culture, group identity and individual autonomy. AB - The literature on team and inter-professional care practice describes numerous barriers to the institutionalization of inter-professional healthcare. Responses to slow institutionalization of inter-professional healthcare practice have failed to describe change variables and to identify change agents relevant to inter-professional healthcare practice. The purpose of this paper is to (1) describe individual and organizational level barriers to collaborative practice in healthcare; (2) identify change variables relevant to the institutionalization of inter-professional practice at individual and organizational levels of analysis; and (3) identify human resource professionals as change agents and describe how the strategic use of the human resource function could transform individual and organizational level change variables and therefore facilitate the healthcare system's shift toward inter-professional practice. A proposed program of institutionalization includes the following components: a strategic plan to align human resource functions with organizational level inter-professional healthcare strategies, activities to enhance professional competencies and the organizational position of human resource personnel, activities to integrate inter-professional healthcare practices into the daily routines of institutional and individual providers, activities to stand up health provider champions as permanent leaders of inter-professional teams with human resource professionals as consultants and activities to bring all key players to the table including health providers. PMID- 22311307 TI - Metabolism of hyperpolarized [1-13C]pyruvate in the isolated perfused rat lung - an ischemia study. AB - We report studies of the effect of ischemia on the metabolic activity of the intact perfused lung and its restoration after a period of reperfusion. Two groups of rat lungs were studied using hyperpolarized 1-(13) C pyruvate to compare the rate of lactate labeling differing only in the temporal ordering of ischemic and normoxic acquisitions. In both cases, a several-fold increase in lactate labeling was observed immediately after a 25-min ischemia event as was its reversal back to the baseline after 30-40 min of resumed perfusion (n = 5, p < 0.025 for both comparisons). These results were corroborated by (31) P spectroscopy and correspond well to measured changes in lactate pool size determined by (1) H spectroscopy of freeze-clamped specimens. PMID- 22311308 TI - EC calls for a unified approach to Schmallenberg virus. PMID- 22311310 TI - EFSA recommends use of animal-based measures when assessing welfare. PMID- 22311311 TI - Defra sets out strategy for dealing with notifiable avian diseases. PMID- 22311313 TI - EC begins action over non-compliance with battery cage ban. PMID- 22311316 TI - Getting to the heart of human and animal cardiology. PMID- 22311318 TI - Cats, cations and hypertension. PMID- 22311319 TI - Prevention of Schmallenberg virus. PMID- 22311320 TI - Laboratory diagnosis of Mycoplasma/Ureaplasma abortion in cattle. PMID- 22311321 TI - Veterinary checks on best of breed winners at Crufts. PMID- 22311322 TI - Donating medicines to welfare projects. PMID- 22311323 TI - Donating medicines to welfare projects. PMID- 22311324 TI - Modernising meat inspection. PMID- 22311330 TI - Nepeta japonica Maximowicz extract from natural products inhibits lipid accumulation. AB - BACKGROUND: To develop novel and crude anti-obesity drugs from natural products is a promising field to approach the solution to a global health problem such as obesity. The aim of this study was to screen crude anti-obesity drugs from 400 natural products on lipase inhibition activity in vitro. RESULTS: Among the natural products examined, 31 extracts showed significantly inhibition activity against porcine pancreatic lipase (triacylglycerol lipase, EC 3.1.1.3) by using spectrophotometry with 2,4-dinitrophenylbutyrate as a substrate. Furthermore, 31 natural products were investigated with regard to their lipid inhibition in 3T3 L1 cells. Among these, one of most promising was Nepeta japonica Maximowicz extract, which showed inhibition of triglyceride accumulation in 3T3-L1 adipocytes, suggesting anti-obesity activity. Also, the amount of glycerol released from cells into the medium was increased by treatment of Nepeta japonica Maximowicz extract at a concentration of 100 ug mL(-1) . CONCLUSION: The present study suggests that a promising crude anti-obesity drug screened from 400 natural products might be of therapeutic interest with respect to the treatment of obesity. PMID- 22311331 TI - Psychosocial and cognitive health differences by caregiver status among older Mexican Americans. AB - This study identifies the risk and protective factors associated with informal caregiving by older (>=70 years) Mexican Americans and profiles caregiving arrangements. Overall, a greater number of informal caregivers (n = 92) were married and female. They also had higher physical functioning and better cognition than non-caregivers (n = 1,888) but fewer visited a physician regularly. Informal caregivers also showed an increased risk of depressive symptoms. A third of caregivers spent more than 20 h/day caregiving and the majority (84%) of care recipients were family members. In order to support the efforts of this disproportionately burdened caregiver group, increased social support and healthcare services are needed. PMID- 22311332 TI - The patient-doctor relationship and online social networks: results of a national survey. PMID- 22311333 TI - Access to and use of $4 generic programs in Medicare. AB - BACKGROUND: Although four-dollar programs ($4 per 30-day supply for selected generic drugs) have become important options for seniors to obtain affordable medications, little is known about access to these programs and the characteristics of those who use them. OBJECTIVES: We quantify access to $4 programs based on driving distance; evaluate factors affecting the program use and potential cost-savings associated with switching to $4 programs in Medicare. DESIGN: Observational study. SETTING: US Medicare Part D data, 5% random sample, 2007 PARTICIPANTS: 347,653 elderly beneficiaries without Medicaid coverage or low income subsidies. MAIN MEASURES: We evaluated how use of $4 programs was affected by driving distance to the store and the beneficiary's demographic and socioeconomic status, insurance coverage, health status, comorbidities, and medication use. For those who did not use the $4 programs, we calculated potential savings from switching to $4 generics. KEY RESULTS: Eighty percent of seniors in Medicare Part D filled prescriptions for generic drugs that were commonly available at $4 programs. Among them, only 16.3% filled drugs through $4 programs. Beneficiaries who lived in poor areas, had less insurance, more co morbidities, and used more drugs and lived closer to $4 generic retail pharmacies, were more likely to use these programs. Blacks were less likely to use the program relative to Whites (15.0% vs. 16.4%; OR=0.75, 95% CI 0.71-0.80). While 53.2% of nonusers would save by switching to $4 program after incorporating travelling costs, 58% of those who could save would have net annual out-of-pocket savings of less than $20. CONCLUSIONS: The take-up rate of $4 programs was low in 2007 among Medicare beneficiaries. As more stores offer $4 programs and increasing numbers of drugs become generic, more beneficiaries could potentially benefit, as could the Medicare program. PMID- 22311334 TI - Electronic medical record availability and primary care depression treatment. AB - BACKGROUND: Electronic medical records (EMR) are commonly believed to improve quality of care. Primary care patients with multiple chronic conditions have potentially greater opportunity to benefit from receiving care at practices with EMRs if these systems help coordinate complex care. OBJECTIVE: To examine how chronic conditions impact the odds that depressed patients receive depression treatment in primary care practices with EMRs compared to practices without EMRs. DESIGN: The study uses logistic regression to analyze cross-sectional data of primary care physician office visits in freestanding, office-based practices from the 2006-2008 National Ambulatory Medical Care Surveys. PATIENTS: All visits to primary care providers made by patients ages 18 and older with physician identified depression (N = 3,467). MAIN MEASURES: Outcomes include depression treatment which is defined as receipt or ordering of antidepressant medication and/or mental health counseling. KEY RESULTS: EMRs were associated with significantly lowered odds that depressed patients received depression treatment (OR = 0.75, p = 0.009, 95% CI: 0.61-0.93); however when stratified by the number of chronic conditions, this association was observed only in patients with three or more chronic conditions (OR = 0.50, p > 0.001, 95% CI: 0.36-0.70). EMRs did not have a significant association with depression treatment for patients with two or fewer chronic conditions. CONCLUSIONS: EMRs appear to have an unintended negative association with depression care provided during visits made by primary care patients with multiple chronic conditions. PMID- 22311335 TI - Personalized therapeutics: a potential threat to health equity. AB - Throughout history, medical advances have been adopted first and preferentially by the well educated and economically advantaged groups. The development of personalized therapeutics holds promise to fundamentally alter the practice of clinical medicine, but if it also is used preferentially by economically advantaged groups, this advance will likely worsen socioeconomic disparities in health. Prospective development of strategies to ensure non- differential access to these therapies may help limit this unintended consequence of medical progress for economically disadvantaged groups. PMID- 22311336 TI - NF-kappaB as a potential therapeutic target in microbial diseases. AB - The failure of conventional vaccines or antimicrobials to combat newly emerging pathogens such as new influenza viruses or antibiotic-resistant bacteria provides significant challenges in the identification of innovative therapeutic approaches and targets for microbial infections. Such therapies, directed towards host-cell molecules, may represent alternative options where conventional approaches face difficulties. We will largely focus on those strategies that directly target the host inflammatory response, specifically those that result in the activation of the nuclear transcription factor (NF)-kappaB. NF-kappaB plays a central role in the cellular stress response and in inflammation by controlling the expression of a network of inducers and effectors that define responses to pathogens. Therefore, the modulation of NF-kappaB activation and its signaling pathway offer an exceptional therapeutical strategy that could benefit from targeting a single host regulatory pathway. The use of NF-kappaB inhibitors or enhancers will be possible only if modulation between the host's and pathogen's advantage can be reached. Since different pathogens have developed various mechanisms to alter the activation of NF-kappaB, the present review will mainly focus on the role of NF kappaB in microbial infections, highlighting its importance as a therapeutic target and reviewing the current understanding of how NF-kappaB inhibition can be considered a potential paradigm for the development of novel antimicrobial therapies. PMID- 22311337 TI - Quo vadis? A dilemma. PMID- 22311340 TI - 1H, 13C and 15N backbone and side chain resonance assignments of human halo S100A1. AB - As part of our NMR structure determination of the Human S100A1, we report nearly complete NMR chemical shift assignments for the (1)H, (13)C and (15)N nuclei. PMID- 22311339 TI - Genetic engineering of a Lemna isoleucine auxotroph. AB - Lemna, a member of the Lemnaceae or duckweed family, is a small aquatic plant that can be quickly transformed to produce recombinant proteins in a contained and controlled bioprocessing environment. The containment capability of Lemna has been further improved with the creation of an auxotroph platform that requires isoleucine supplementation for survival of transformed plant lines. Using an RNAi based approach, threonine deaminase (TD) expression was targeted and thus resulted in dramatically reduced expression of this key enzyme in the isoleucine biosynthesis pathway. Auxotrophic plants expressing RNAi for TD were generated in the presence of isoleucine and selected based on their inability to propagate without isoleucine supplementation. TD transcripts isolated from the superior auxotroph lines were shown to be less than 10% of wild type level and thus confirmed the auxotroph phenotype to be derived from the specific knock down of TD expression. When grown under optimal conditions with appropriate isoleucine supplementation, biomass accumulation of the auxotroph lines was equivalent to that of wild type plants. To demonstrate the application of this system for production of recombinant proteins, an avian influenza H5N1 hemagglutinin (HA) protein was expressed in the isoleucine auxotroph platform. The successful expression of H5N1 HA vaccine antigen, in the isoleucine auxotroph background demonstrates the applicability of using an auxotroph to express biotherapeutics and vaccines in a highly contained expression system. PMID- 22311341 TI - Incidence and subtypes of MCI and dementia 1 year after first-ever stroke in patients without pre-existing cognitive impairment. AB - BACKGROUND: Post-stroke dementia is defined as any dementia occurring after stroke, and includes vascular, degenerative and mixed dementia. The aim of this study was to assess the incidence of dementia and mild cognitive impairment (MCI) one year after stroke in a population free from pre-stroke cognitive decline, and to investigate the different aetiological subtypes of post-stroke dementia and MCI, using a novel method of subclassification in order to separate vascular causes of MCI or dementia from a neurodegenerative disease. METHODS: All patients with a first-ever stroke and TIA admitted to the stroke unit of Asker and Baerum Hospital were invited. After 12 months, dementia and MCI were diagnosed. Sub classification was made using MRI findings, the results of biomarkers in cerebrospinal fluid and the patients' clinical cognitive profile. RESULTS: 36 (19.6%) patients developed dementia during the first year after stroke and 69 (37.5%) developed MCI. Fourteen (13.3%) were diagnosed as suffering from degenerative cognitive disease, 34 (32.4%) from vascular cognitive disease, and 57 (54.3%) from mixed disease. CONCLUSION: Fifty-seven percent suffered from cognitive impairment one year after stroke and only one third from isolated vascular cognitive disease. Post-stroke cognitive impairment is complex with a high coexistence of vascular and degenerative changes. PMID- 22311342 TI - Outcome of Henoch-Schonlein purpura 8 years after treatment with a placebo or prednisone at disease onset. AB - BACKGROUND: Corticosteroids have been shown not to prevent the development of Henoch-Schonlein nephritis. However, long-term follow-up data are scarce. METHODS: The long-term outcome of patients in a randomized placebo-controlled prednisone study was evaluated 8 years later with a health questionnaire completed by 160/171 (94%) patients and by urine and blood pressure screening (138/171, 81%). RESULTS: Twelve patients had hematuria and/or proteinuria and seven had hypertension. The patients with nephritis at onset of Henoch-Schonlein purpura (HSP) had an increased risk of hypertension and/or urine abnormalities (odds ratio 3.6, p = 0.022, 95% confidence interval 1.3-10.0). There were no differences between the prednisone and placebo groups. Recurrences of purpura were reported by 15 patients, with some recurrences continuing for 10 years. All five reported pregnancies were complicated by proteinuria. Four patients presented with hematuria and/or proteinuria at the control visit, and four had hypertension. Of these, two had a decreased estimated glomerular filtration rate. CONCLUSIONS: HSP has a good long-term prognosis in unselected patients, although skin relapses with/without late-onset nephritis may occur, even a decade after the initial disease. Urine and blood pressure abnormalities 8 years after HSP are associated with nephritis at its onset. Early prednisone treatment does not affect the outcome and should not be routinely used. PMID- 22311343 TI - Uric acid and IGF1 as possible determinants of FGF23 metabolism in children with normal renal function. AB - BACKGROUND: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone and a suppressor of renal 1alpha hydroxylase. Although circulating values of FGF23 are increased in early chronic kidney disease (CKD), the interplay between FGF23 levels, growth and nutritional biomarkers has not been evaluated in children with normal renal function. METHODS: We performed a secondary analysis of the cross sectional observational INU23 study in 98 children (51 boys, mean age 10.5 +/- 3.9 years) with preserved renal function (glomerular filtration rate (GFR) 114 +/ 14 ml/min/1.73 m(2)). RESULTS: In bivariate analyses, C-terminal FGF23 levels were positively related to phosphorus and uric acid levels. Intact FGF23 levels were positively associated with uric acid and insulin growth factor 1 (IGF1) levels, with similar results for age, body mass index (BMI), and 25OH vitamin D (25(OH)D). By multivariable analyses, 25(OH)D, uric acid, and phosphorus were independent predictors of C-terminal FGF23, while 25(OH)D, uric acid, and IGF1 were independent predictors of intact FGF23. CONCLUSIONS: In children with preserved kidney function, the association between FGF23, uric acid, and IGF1 suggests that FGF23 could be an early nutritional indicator of high protein and phosphate intake. The association between FGF23 and IGF1 also suggests a relationship between FGF23 and growth, and warrants further investigation. PMID- 22311344 TI - Glucocorticoids regulate gene expression and repress cellular proliferation in human uterine leiomyoma cells. AB - Sex hormones and growth factors have been implicated in the pathogenesis of uterine leiomyomas. The uterus is also an abundant source of the glucocorticoid receptor but its role and function have been largely ignored. Human samples of uterine leiomyomas and matched myometrium retain expression of the glucocorticoid receptor (GR) suggesting a potential role for GR in leiomyoma function. However, hormone responsive gene expression varies between normal myometrium and leiomyoma cells. We now employ genome-wide microarray studies comparing glucocorticoid and estrogen-treated human uterine leiomyoma cells to those treated with both steroids to identify the potential role of glucocorticoids in uterine leiomyoma cells. Treatment with the synthetic glucocorticoid dexamethasone (Dex) regulated 3,128 probes. Estrogen (E(2)) treatment identified 2,094 probes, and in the presence of both hormones, 4,626 probes were regulated. Of the 552 probes identified, the majority of genes co-regulated by Dex, E(2), and Dex + E(2) exhibited co-downregulation. Interestingly, a small group of 17 genes displayed antagonistic regulation by Dex and E(2), where all genes in this group, Dex reversed the E(2) effect with. Ingenuity Pathway Analysis of the data identified cell growth, development, and differentiation as significant glucocorticoid regulated pathways. Flow cytometry confirmed that glucocorticoids regulated cell proliferation and significantly reduced the percentage of S-phase cells either in the presence or absence of estrogen in leiomyomas but not smooth muscle cells. Translation of our results suggest that glucocorticoids may play a significant role in regulating uterine leiomyoma gene expression and cell growth, and thus may have implications for therapeutic development of uterine leiomyoma treatment. PMID- 22311345 TI - Abnormal DAT SCAN in a patient with parkinsonism after a midbrain ischemic lesion. PMID- 22311346 TI - Simultaneous bilateral hip joint imaging at 7 Tesla using fast transmit B1 shimming methods and multichannel transmission - a feasibility study. AB - The objective of this study was to demonstrate the feasibility of simultaneous bilateral hip imaging at 7 Tesla. Hip joint MRI becomes clinically critical since recent advances have made hip arthroscopy an efficacious approach to treat a variety of early hip diseases. The success of these treatments requires a reliable and accurate diagnosis of intraarticular abnormalities at an early stage. Articular cartilage assessment is especially important to guide surgical decisions but is difficult to achieve with current MR methods. Because of gains in tissue contrast and spatial resolution reported at ultra high magnetic fields, there are strong expectations that imaging the hip joint at 7 Tesla will improve diagnostic accuracy. Furthermore, there is growing evidence that the majority of these hip abnormalities occur bilaterally, emphasizing the need for bilateral imaging. However, obtaining high quality images in the human torso, in particular of both hips simultaneously, must overcome a major challenge arising from the damped traveling wave behaviour of RF waves at 7 Tesla that leads to severe inhomogeneities in transmit B1 (B(1) (+) ) phase and magnitude, typically resulting in areas of low signal and contrast, and consequently impairing use for clinical applications. To overcome this problem, a 16-channel stripline transceiver RF coil was used, together with a B1 shimming algorithm aiming at maximizing B(1) (+) in six regions of interest over the hips that were identified on axial scout images. Our successful results demonstrate that this approach effectively reduces inhomogeneities observed before B1 shimming and provides high joint tissue contrast in both hips while reducing the required RF power. Critical to this success was a fast small flip angle B(1) (+) calibration scan that permitted the computation of subject-specific B1 shimming solutions, a necessary step to account for large spatial variations in B(1) (+) phase observed in different subjects. PMID- 22311347 TI - Changes in the expression of extracellular regulated kinase (ERK 1/2) in the R6/2 mouse model of Huntington's disease after phosphodiesterase IV inhibition. AB - The mitogen-activated protein kinases (MAPKs) superfamily comprises three major signaling pathways: the extracellular signal-regulated protein kinases (ERKs), the c-Jun N-terminal kinases or stress-activated protein kinases (JNKs/SAPKs) and the p38 family of kinases. ERK 1/2 signaling has been implicated in a number of neurodegenerative disorders, including Huntington's disease (HD). Phosphorylation patterns of ERK 1/2 and JNK are altered in cell models of HD. In this study, we aimed at studying the correlations between ERK 1/2 and the neuronal vulnerability to HD degeneration in the R6/2 transgenic mouse model of HD. Single and double label immunofluorescence for phospho-ERK (pERK, the activated form of ERK) and for each of the striatal neuronal markers were employed on perfusion-fixed brain sections from R6/2 and wild-type mice. Moreover, Phosphodiesterase 4 inhibition through rolipram was used to study the effects on pERK expression in the different types of striatal neurons. We completed our study with western blot analysis. Our study shows that pERK levels increase with age in the medium spiny striatal neurons and in the parvalbumin interneurons, and that rolipram counteracts such increase in pERK. Conversely, cholinergic and somatostatinergic interneurons of the striatum contain higher levels of pERK in the R6/2 mice compared to the controls. Rolipram induces an increase in pERK expression in these interneurons. Thus, our study confirms and extends the concept that the expression of phosphorylated ERK 1/2 is related to neuronal vulnerability and is implicated in the pathophysiology of cell death in HD. PMID- 22311348 TI - Differential expression of potassium channels and abnormal conduction in experimental tachycardia-induced heart failure. AB - Heart failure causes electrophysiological changes in the heart. Downregulation of repolarizing K+-currents leads to a prolongation of the cardiac action potential. Nevertheless, little is known about the differential expression of atrial and ventricular K+-channels in the failing heart. Ten rabbits underwent progressive rapid right ventricular pacing for 30 days. Digitized ECGs and echocardiograms were obtained. Left ventricular and left atrial tissue was harvested and mRNA levels of BNP, Kv4.3, rERG, Kv1.5, and KvLQT1 were measured by real time PCR. Experimental heart failure was characterized by left ventricular dilatation (13 +/- 1 mm vs. 9 +/- 1, p < .001), depressed fractional shortening (25 +/- 5% vs. 40 +/- 4, p < .001), and left atrial remodeling with increased diameter (16 mm +/ 2 vs. 12 +/- 1, p = .002) and weight (1.3 g +/- 0.2 vs. 0.5 +/- 0.1, p = .01). A prolongation of P-wave (44 +/- 5 ms vs. 40 +/- 4, p = .001) and PQ-interval (73 +/- 10 ms vs. 66 +/- 9, p = .009) occurred. In heart failure, BNP mRNA levels showed a significant upregulation in the left ventricle and atrium (1.83 AU +/ 1.31 vs. 0.67 +/- 0.65, p < .05 and 7.16 AU +/-1.76 vs. 0.77 +/- 0.48, p < .05). Left ventricular Kv1.5 mRNA was reduced by 50% (p < .001) and KvLQT1 was reduced by 70% (p < .001). rERG and Kv4.3 mRNA were unchanged (n = ns). In contrast, left atrial Kv4.3 and KvLQT1 were reduced by 70% (p < .001), whereas rERG and Kv1.5 were unchanged (p = ns). Significant correlations were present between BNP and K+ channel expressions. Heart failure is characterized by significant changes in the gene expression of repolarizing K+-currents with a differential atrial and ventricular pattern. These molecular changes occur together with changes in cardiac function, geometry, conduction, and BNP expression and provide a functional basis for electrical vulnerability in heart failure. PMID- 22311349 TI - Inhibition of TNF-alpha protects against hepatic ischemia-reperfusion injury in rats via NF-kappaB dependent pathway. AB - Hepatic ischemia-reperfusion injury (I/R) is a serious health problem associated with liver transplantation, resection surgery, and various types of shock especially hemorrhagic shock. In the present investigation, the effect of inhibition of tumor necrosis factor-alpha (TNF-alpha) using pentoxifylline or infliximab against hepatic I/R injury induced in rats by 45-min ischemia and 1-h reperfusion was studied. It was observed that both pentoxifylline and infliximab treated groups showed a significantly lower extent and severity of liver injury. This is attributed to (1) a decrease in oxidative stress markers, (2) reduction of the expression of TNF-alpha, TNF-alpha type-1 receptors, and nuclear factor kappa B (NF-kappaB). Thus TNF-alpha inhibition may be one of the therapeutic interventions to overcome the deleterious effects of I/R on liver via reduction of oxidative stress and inhibition of inflammatory cascade. PMID- 22311351 TI - Projects funded by the Research Fund for the Control of Infectious Diseases. PMID- 22311350 TI - Protective role of somatostatin receptor 2 against retinal degeneration in response to hypoxia. AB - In mouse retinal explants, octreotide, a somatostatin [somatotropin release inhibiting factor (SRIF)] receptor 2 (sst(2)) agonist, prevents the hypoxia induced vascular endothelial growth factor upregulation. In mice with oxygen induced retinopathy (OIR), a model of retinopathy of prematurity, either sst(2) overexpression or octreotide have been found to limit hypoxia-induced angiogenic processes. Here, we investigated whether sst(2) influences retinal degeneration in response to hypoxia in wild-type (WT), sst(1)- and sst(2)-knockout (KO) mice. In retinal explants, we determined the role of sst(2) on apoptotic signals. In control condition, caspase-3 activity and the Bax/Bcl-2 ratio were lower in sst(1)-KO than in WT, but higher in sst(2)-KO than in WT retinas. In all strains, a comparable increase in caspase-3 activity and the Bax/Bcl-2 ratio was observed after hypoxia. The hypoxia-induced increase in apoptotic signals was recovered by octreotide in both WT and sst(1)-KO retinas. To investigate the role of sst(2) on retinal function, we recorded electroretinogram (ERG) in response to light flashes in OIR mice. ERG responses did not differ between WT and KO mice with the exception of oscillatory potentials (OPs) which, in sst(1)-KO mice, displayed much larger amplitude. In all strains, hypoxia drastically reduced a-, b-waves and OPs. In both WT and sst(1)-KO mice, octreotide recovered a- and b-waves, but did not recover OPs in sst(1)-KO mice. Neither apoptotic signals nor ERG was affected by octreotide in sst(2)-KO mice. These results show that sst(2) may protect retinal cells from hypoxia, thus implementing the background to establish potential pharmacological targets based on sst(2) pharmacology. PMID- 22311352 TI - Influenza vaccination and hospitalisation in Elderly Health Centres. AB - 1. A cohort of Elderly Health Centres was examined to determine whether influenza vaccination decreased hospitalisation and mortality. 2. In the influenza season, influenza vaccination reduced all-cause mortality by half and cardiorespiratory hospitalisation by a quarter. The extent to which influenza vaccination protects older people from serious morbidity and mortality needs to be confirmed in appropriately designed studies, so that scarce health care resources can be used effectively PMID- 22311353 TI - Effect of influenza on cardiorespiratory and all-cause mortality in Hong Kong, Singapore and Guangzhou. AB - 1. Using a common modelling approach, mortality attributable to influenza was higher in the two subtropical cities Guangzhou and Hong Kong than in the tropical city Singapore. 2. The virus activity appeared more synchronised in subtropical cities, whereas seasonality of influenza tended to be less marked in the tropical city. 3. High temperature was associated with increased mortality after influenza infection in Hong Kong, whereas relative humidity was an effect modifier for influenza in Guangzhou. No effect modification was found for Singapore. 4. Seasonal and environmental factors probably play a more important role than socioeconomic factors in regulating seasonality and disease burden of influenza. Further studies are needed in identifying the mechanism behind the regulatory role of environmental factors. PMID- 22311354 TI - Interferon dysregulation and virus-induced cell death in avian influenza H5N1 virus infections. AB - 1. Hyper-induction of cytokines and chemokines was found in human blood macrophages infected with the avian influenza H5N1 and H9N2/G1 viruses, as compared to those infected with human influenza H1N1 virus. 2. IRF3 played a significant role in the hyperinduction of cytokines including IFN-beta, IFN lambda1,IFN-alpha subtypes, MCP-1, and TNF-alpha, and also played a part in subsequent cytokine-induced cell signalling cascades. 3. Compared with H1N1 viruses, avian influenza viruses including H5N1/97 and its precursors triggered a caspase-mediated but delayed apoptotic response in human macrophages. 4. Therapies that can minimise immunopathology-associated dysregulation of innate immunity without impairing effective host defence may be valuable adjuncts to antiviral therapy. PMID- 22311355 TI - Human immunogenic T cell epitopes in nucleoprotein of human influenza A (H5N1) virus. AB - 1. Two novel HLA-A2.1 specific H5N1 nucleoprotein epitopes(NP373-381 AMDSNTLEL and NP458-466 FQGRGVFEL) capable of activating cytotoxic T-cells in vitro were identified. 2. When the H5N1 nucleoprotein epitopes (NP373-381AMDSNTLEL and NP458 466FQGRGVFEL) were used with the single chain trimer system, they elicited effective cytotoxic T-cell responses against the corresponding nucleoprotein peptide-loaded cells in an HHD transgenic mouse model. PMID- 22311356 TI - Epidemiology of coronavirus-associated respiratory tract infections and the role of rapid diagnostic tests: a prospective study. AB - 1. Coronaviruses accounted for 1.6% (98/6272) of respiratory tract infections based on nasopharyngeal aspirate samples. 2. HCoV-OC43 was the most common coronavirus detected,followed by HCoV-NL63, CoVHKU1,and HCoV-229E. 3. Although CoV-HKU1 infections were most often associated with the upper respiratory tract, more severe illness (pneumonia,acute bronchiolitis, and asthmatic exacerbation) may occur, especially in those with underlying disease. In young children, CoV HKU1 infection is associated with a high rate of febrile seizures (50%). 4. CoV HKU1 and HCoV-OC43 infections peaked in winter, in contrast to HCoV-NL63, which mainly occurred in early summer and autumn, but was absent in winter. 5. Reverse transcriptase polymerase chain reaction is useful for the rapid diagnosis of coronavirus infections. PMID- 22311357 TI - Wild animal surveillance for coronavirus HKU1 and potential variants of other coronaviruses. AB - 1. Although CoV-HKU1 was not identified in any of the studied animals, a coronavirus closely related to SARS-CoV (bat-SARS-CoV) was identified in 23 (19%) of 118 wild Chinese horseshoe bats by reverse transcriptase polymerase chain reaction (RT-PCR). 2. Complete genome sequencing and phylogenetic analysis showed that bat-SARS-CoV formed a distinct cluster with SARS-CoV as group 2b coronaviruses, distantly related to known group 2 coronaviruses. 3. Most differences between the bat-SARS-CoV and SARS-CoV genomes were observed in the spike gene. The presence of a29-bp insertion in ORF 8 of bat-SARS-CoV genome, not in most human SARS-CoV genomes, suggests that it has a common ancestor with civet SARS-CoV. 4. Antibody against recombinant bat-SARS-CoV nucleocapsid protein was detected in 84% of Chinese horseshoe bats using an enzyme immunoassay.Neutralising antibody to human SARS-CoV was also detected in those with lower viral loads.5. This study also revealed a previously unknown diversity of coronaviruses in bats, which are important natural reservoir for coronaviruses including SARS-CoV-like viruses. PMID- 22311358 TI - Human coronavirus NL63 in children: epidemiology, disease spectrum, and genetic diversity. AB - 1. Human coronaviruses (HCoVs)were detected in 2.5% of 2982 local children hospitalised for acute respiratory infections in 2005 to 2007. 2. Using the 'pancoronavirus' reverse transcription-polymerase chain reaction assay, detection rates were 0.6% for HCoVNL63,1.2% for HCoV-OC43,0.5% for HCoV-HKU1, and 0.2% for HCoV-229E. Notably, HCoV-NL63 infections were significantly more common among children hospitalised in 2006/2007 (1.2%) than in 2005/2006 (0.3%).3. The peak season for HCoVNL63 infection was autumn(September to October). 4. HCoV-NL63 infection was associated with younger age,croup, febrile convulsion, and acute gastroenteritis. Such disease associations were not found with the other three HCoVs. 5. Most local HCoV-NL63 isolates were closely related to the prototype strain in Netherlands(NL496), but a few were phylogenetically distinct from the major cluster. PMID- 22311359 TI - SARS CoV subunit vaccine: antibody-mediated neutralisation and enhancement. AB - 1. A SARS vaccine was produced based on recombinant native full-length Spike protein trimers (triSpike) and efficient establishment of a vaccination procedure in rodents. 2. Antibody-mediated enhancement of SARS-CoV infection with anti-SARS CoV Spike immune-serum was observed in vitro. 3. Antibody-mediated infection of SARS-CoV triggers entry into human haematopoietic cells via an FcgammaR-dependent and ACE2-, pH-, cysteine-protease-independent pathways. 4. The antibody-mediated enhancement phenomenon is not a mandatory component of the humoral immune response elicited by SARS vaccines, as pure neutralising antibody only could be obtained. 5. Occurrence of immune-mediated enhancement of SARS-CoV infection raises safety concerns regarding the use of SARS-CoV vaccine in humans and enables new ways to investigate SARS pathogenesis (tropism and immune response deregulation). PMID- 22311360 TI - Public health interventions to control the spread of a directly transmitted human pathogen within and between Hong Kong and Guangzhou. AB - The ability to detect and differentiate between fast and slow spatial spread of infectious disease depends on the density of the surveillance network. 2. The results of this study suggest that more concentrated surveillance networks are required in Guangzhou compared with other regions, such as Thailand and Europe, as long-distance travel is less frequent. PMID- 22311361 TI - Inter-flat airflow and airborne disease transmission in high-rise residential buildings. AB - 1. A virus-spread mechanism is related to inter-flat or interzonal airflow through open windows caused by buoyancy effects. 2. Both on-site measurements and numerical simulations quantify the amount of the exhaust air that exits the upper part of the window of a floor and re-enters the lower part of the open window of the immediately upper floor. 3. Ventilation air could contain up to 7% (in terms of mass fraction) of the exhaust air from the lower floor.4. In high-rise buildings, windows flush with the facade are a major route for the vertical spread of pathogen-containing aerosols, especially those<1 MUm in diameter. PMID- 22311362 TI - Neuroprotective effects of minocycline on double-stranded RNA-induced neurotoxicity in cultured cortical neurons. AB - 1. Minocycline, memantine,and glycoconjugate were assessed for their ability to protect cultured primary cortical neurons against double-stranded RNA-induced neurotoxicity. 2. Minocycline but not memantine or glycoconjugate protected cultured cells and warrants further investigation. PMID- 22311363 TI - Transmission of Japanese encephalitis virus in Hong Kong. AB - 1. Pigs are likely to be the main amplifying host for Japanese encephalitis virus. 2. The success of a swine vaccination programme depends on the timing of the loss of maternal antibody protection and seasonal dynamics of the vector population. 3. Vaccination may be ineffective in the face of strong natural infection because of the variability in timing of the loss of maternal antibody protection.4. Evidence in support of swine vaccination as a human health intervention was not found. PMID- 22311364 TI - Reduced cerebral oxygen saturation during thoracic surgery predicts early postoperative cognitive dysfunction. AB - BACKGROUND: The objective of this prospective study is to determine cognitive dysfunction after thoracic surgery. METHODS: Seventy-six patients undergoing thoracic surgery with single-lung ventilation (SLV) of an expected duration of >45 min were enrolled. Monitoring consisted of standard clinical parameters and absolute oximetry (S(ct)O(2)). The Mini-Mental State Exam (MMSE) test was used to assess cognitive function before operation and at 3 and 24 h after operation. Data were analysed using Spearman correlation test; risks for cognitive dysfunction were expressed as odds ratios. P<0.05 and data are presented as median (interquartile range). RESULTS: One patient was excluded from the study. S(ct)O(2) during SLV decreased to critical values of <65%, 60%, and 55% in 40 (53%), 15 (20%), and 5 patients (7%), respectively. Twenty-two patients (29%) had a decrease of MMSE>2 points 3 h after surgery, eight patients (10%) had a decrease of MMSE>2 points 24 h after surgery. Postoperative cognitive dysfunction correlated at r(2)=0.272, 0.285, 0.297 with patient exposure times to S(ct)O(2)<65% (P=0.018), <60% (P=0.013), <55% (P=0.010), respectively. The odds ratios of developing early cognitive dysfunction ranged from 2.03 (95% CI: 0.74 5.59) for a short (<5 min) exposure to S(ct)O(2)<65% to a maximum of 9.56 (95% CI: 1.75-52.13) when S(ct)O(2) was <60% for more than 30 min. CONCLUSIONS: Early cognitive dysfunction after thoracic surgery with SLV is positively related to intraoperative decline of S(ct)O(2). PMID- 22311365 TI - Impact of loss of high-molecular-weight von Willebrand factor multimers on blood loss after aortic valve replacement. AB - BACKGROUND: Severe aortic stenosis is associated with loss of the largest von Willebrand factor (vWF) multimers, which could affect primary haemostasis. We hypothesized that the altered multimer structure with the loss of the largest multimers increases postoperative bleeding in patients undergoing aortic valve replacement. METHODS: We prospectively included 60 subjects with severe aortic stenosis. Before and after aortic valve replacement, vWF antigen, activity, and multimer structure were determined and platelet function was measured by impedance aggregometry. Blood loss from mediastinal drainage and the use of blood and haemostatic products were evaluated perioperatively. RESULTS: Before operation, the altered multimer structure was present in 48 subjects (80%). Baseline characteristics and laboratory data were similar in all subjects. The median blood loss after 6 h was 250 (105-400) and 145 (85-240) ml in the groups with the altered and normal multimer structures, respectively (P=0.182). After 24 h, the cumulative loss was 495 (270-650) and 375 (310-600) ml in the groups with the altered and normal multimer structures, respectively (P=0.713). Multivariable analysis revealed no significant influence of multimer structure and platelet function on bleeding volumes after 6 and 24 h. After 24 h, there was no obvious difference in vWF antigen, activity, and multimer structure in subjects with and without the altered multimer structure before operation or in subjects with and without perioperative plasma transfusion. CONCLUSIONS: The altered vWF multimer structure before operation was not associated with increased bleeding after aortic valve replacement. Our findings might be explained by perioperative release of vWF and rapid recovery of the largest vWF multimers. PMID- 22311366 TI - Assessment of variables associated with smoking cessation in Crohn's disease. AB - BACKGROUND: Patients with Crohn's disease (CD) who smoke have a more complicated disease course. AIMS: Our primary objective was to assess smoking related variables that were associated with smoking cessation versus continued smoking in patients with CD. METHODS: A multi-center study identified CD patients who were seen at the University of Chicago and University of Calgary IBD clinics. Patients were categorized into three subgroups: lifetime non-smokers, current smokers, or ex-smokers. Participants completed questionnaires assessing their cigarette smoking behavior. Current smokers were prospectively followed for 6 months to assess smoking status and attempts to quit. Logistic regression analysis was performed to identify factors associated with smoking cessation. RESULTS: Three hundred patients were enrolled with 148 identifying themselves as lifetime non smokers, 70 as current smokers, and 82 as ex-smokers. Patients who reported their first cigarette within 5 min of waking were more likely to be current smokers (OR = 21; 95% CI 3.94-107.3) as compared to patients who waited greater than 60 min. Current smokers were more likely to have one or more household members who smoked compared to ex-smokers (P < 0.05). Nearly half (49%) of the current smokers were in the precontemplation stage of change (i.e. no intention to quit smoking). At the 6-month follow-up, only 11% reported they quit smoking. CONCLUSIONS: Patients who report a short time to first cigarette in the morning may have more difficulty in smoking cessation. Current smokers were more likely to have another smoker in the household compared to ex-smokers. Current smokers had low levels of motivation to quit smoking and consequently with no intervention, very few quit 6 months after the baseline assessment. PMID- 22311367 TI - ASCA IgG and CBir antibodies are associated with the development of Crohn's disease and fistulae following ileal pouch-anal anastomosis. AB - BACKGROUND: For ulcerative colitis (UC) patients undergoing ileal pouch-anal anastomosis (IPAA), postoperative complications include chronic pouchitis and development of Crohn's disease (CD) of the pouch. AIMS: The aim of this study was to determine if serologic markers obtained postoperatively are associated with the development of complications in UC patients after IPAA. METHODS: A retrospective chart review was conducted of UC patients with IPAA were tested for expression of serologic markers. Complications abstracted from medical records included postoperative fistula, CD of the pouch, chronic pouchitis, and diversion or excision of the pouch. RESULTS: 142 patients were enrolled, 44 of whom developed complications. Positive serologic profiles for ASCA IgG and anti-CBir1 markers were found to be associated with the development of any complication, (P = 0.017 and P = 0.002, respectively). A positive anti-CBir1 test was also found to be associated with CD of the pouch and/or fistula formation (P < 0.001). Similarly, both ASCA IgG and anti-CBir1 titers were significantly associated with postoperative IPAA complications (P = 0.034 and P = 0.001, respectively), and anti-CBir1 titers were associated with CD of the pouch and/or fistula formation (P < 0.001). Complications developed after a median follow-up of 216 months (range 1-264). CONCLUSIONS: ASCA IgG and anti-CBir1 markers were associated with the development of complications after IPAA, specifically fistulae and/or CD of the pouch. The ability to identify patients at high risk for adverse outcomes may allow for early aggressive therapy, which may decrease the rate of pouch failure. A prospective study of patients with preoperative serology is ongoing. PMID- 22311368 TI - Mechanisms linking nonalcoholic fatty liver disease with coronary artery disease. PMID- 22311369 TI - Safety of capsule endoscopy using human body communication in patients with cardiac devices. AB - BACKGROUND: The MiroCam (IntroMedic, Ltd., Seoul, Korea) is a small-bowel capsule endoscope that uses human body communication to transmit data. The potential interactions between cardiac devices and the capsule endoscope are causes for concern, but no data are available for this matter. AIM: This clinical study was designed to evaluate the potential influence of the MiroCam capsules on cardiac devices. METHODS: Patients with cardiac pacemakers or implantable cardiac defibrillators referred for evaluation of small bowel disease were prospectively enrolled in this study. Before capsule endoscopy, a cardiologist checked baseline electrocardiograms and functions of the cardiac devices. Cardiac rhythms were continuously monitored by 24-h telemetry during capsule endoscopy in the hospital. After completion of procedures, functions of the cardiac devices were checked again for interference. Images from the capsule endoscopy were reviewed and analyzed for technical problems. RESULTS: Six patients, three with pacemakers and three with implantable cardiac defibrillators, were included in the study. We identified no disturbances in the cardiac devices and no arrhythmias detected on telemetry monitoring during capsule endoscopy. No significant changes in the programmed parameters of the cardiac devices were noted after capsule endoscopy. There were no imaging disturbances from the cardiac devices on capsule endoscopy. CONCLUSIONS: Capsule endoscopy using human body communication to transmit data was safely performed in patients with cardiac pacemakers or implantable cardiac defibrillators. Images from the capsule endoscopy were not affected by cardiac devices. A further large-scale study is required to confirm the safety of capsule endoscopy with various types of cardiac devices. PMID- 22311370 TI - Use of the numerator relationship matrix in genetic analysis of autopolyploid species. AB - Mixed models incorporating the inverse of a numerator relationship matrix (NRM) are widely used to estimate genetic parameters and to predict breeding values in animal breeding. A simple and quick method to directly calculate the inverse of the NRM has been historically developed for diploid animal species. Mixed models are less used in plant breeding partly because the existing method for diploids is not applicable to autopolyploid species. This is because of the phenomenon of double reduction and the possibility that gametes carry alleles which are identical by descent. This paper generalises the NRM and its inverse for autopolyploid species, so it can be easily incorporated into their genetic analysis. The technique proposed is to first calculate the kinship coefficient matrix and its inverse as a precursor to calculating the NRM and its inverse. This allows the NRM to be calculated for populations containing individuals of mixed ploidy levels. This generalization can also accommodate uncertain parentage by generating the "average" relationship matrix. The possibility that non-inbred parents can produce inbred progeny (double reduction) is also discussed. Rules are outlined that are applicable for any level of ploidy. Examples of use of the matrix are provided using simulated pedigrees. PMID- 22311371 TI - Identification of Indica rice chromosome segments for the improvement of Japonica inbreds and hybrids. AB - Exploitation of heterosis has brought significant advance in plant breeding and agricultural production, although its genetic basis is still poorly understood. In this study, a total of 66 chromosome segment substitution (CSS) lines, derived from a cross between japonica rice inbred line Asominori (as the recurrent parent) and indica rice inbred line IR24 (as the donor parent), were used to investigate the genetic basis of heterosis in indica * japonica inter-subspecific rice hybrids. Each CSS line was crossed with the background parent Asominori, and the heterosis of F(1) hybrids was estimated by comparing the F(1) performance with its two parental lines. Field experiments were carried out across six different environments to evaluate yield and yield-related traits in the 66 CSS lines and their 66 corresponding F(1) hybrids. Quantitative trait loci (QTL) analyses were conducted using a likelihood ratio test based on the stepwise regression. Thirty-six QTL were identified with significant effects in CSSL, 21 with significant effects in hybrids and 13 with significant effects in both. On the basis of average dominance degree, of all the 70 QTL affecting yield-related agronomic traits, 28.6% (20) showed an overdominance, 35.7% (25) a partial dominance and 30% (21) an additive effect, indicating that all effects contribute to trait variation in japonica-indica rice hybrids. Effects of these QTL were examined to identify Indica rice chromosome segments of interest for the improvement of japonica inbred lines and hybrids. PMID- 22311373 TI - In reference to Evolution of eustachian tube surgery. PMID- 22311372 TI - Genetic mapping of new seed-expressed polyphenol oxidase genes in wheat (Triticum aestivum L.). AB - Polyphenol oxidase (PPO) enzymatic activity is a major cause in time-dependent discoloration in wheat dough products. The PPO-A1 and PPO-D1 genes have been shown to contribute to wheat kernel PPO activity. Recently a novel PPO gene family consisting of the PPO-A2, PPO-B2, and PPO-D2 genes has been identified and shown to be expressed in wheat kernels. In this study, the sequences of these five kernel PPO genes were determined for the spring wheat cultivars Louise and Penawawa. The two cultivars were found to be polymorphic at each of the PPO loci. Three novel alleles were isolated from Louise. The Louise X Penawawa mapping population was used to genetically map all five PPO genes. All map to the long arm of homeologous group 2 chromosomes. PPO-A2 was found to be located 8.9 cM proximal to PPO-A1 on the long arm of chromosome 2A. Similarly, PPO-D1 and PPO-D2 were separated by 10.7 cM on the long arm of chromosome 2D. PPO-B2 mapped to the long arm of chromosome 2B and was the site of a novel QTL for polyphenol oxidase activity. Five other PPO QTL were identified in this study. One QTL corresponds to the previously described PPO-D1 locus, one QTL corresponds to the PPO-D2 locus, whereas the remaining three are located on chromosome 2B. PMID- 22311374 TI - Transcriptional expression profile of cultured human embryonic stem cells in vitro and in vivo. AB - The aims of this study were to analyze the spontaneous differentiation of human embryonic stem cells in vitro and in vivo and to investigate the influence of in vitro partial differentiation on in vivo teratoma formation in immunodeficient mice. Standardized methods are needed for long-term cultivation of undifferentiated stem cells and the multilineage cells that spontaneously differentiate from them. Accordingly, SA002 human embryonic stem cells were cultured on irradiated mouse embryonic fibroblasts cells, on irradiated human foreskin fibroblasts, or were cultured feeder-free using matrigel. Expression of marker protein transcripts was analyzed in undifferentiated and differentiated stem cells using real-time PCR, and both types of stem cells were transplanted subcutaneously into immunodeficient NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice to test for teratoma formation. Teratoma histology and expression profiles were subsequently characterized. Cells cultured using different conditions and morphologically undifferentiated cells had comparable marker expression profiles, showing high expression levels of markers for pluripotency and low-to-moderate expression levels of germ layer markers. Cells showing spontaneous differentiation that were cultured in feeder-free conditions in the absence of basic fibroblast growth factor demonstrated slight upregulation of sex determining region Y-box 17, connexin 32, and albumin expression at early time points, as well as expression of octamer-binding transcription factor 4, proteoglycan epitopes on podocalyxin (Trafalgar), and alkaline phosphatase. At later time points, expression of hepatocyte nuclear factor-3-beta, and hepatocyte nuclear factor-4-alpha and alpha fetoprotein was upregulated, whereas beta-3 tubulin, chemokine receptor, nestin, sex-determining region Y-box 17, and connexin 32 were downregulated. Expression of pluripotency markers remained high, and hematopoetic markers were not expressed. SA002 cells that showed spontaneous partial differentiation in vitro had a low teratoma formation capacity in vivo. Cells that were partially differentiated led to slower growing teratomas with more uniform histology. PMID- 22311375 TI - Exploring physical activity level in patients with thoracic cancer: implications for use as an outcome measure. AB - PURPOSE: Cachexia is common in patients with thoracic cancer impairing physical function and quality of life. New approaches which target muscle tissue are emerging and activity monitors could provide an objective assessment of their effect on physical function. We have collated data from three studies involving the use of one such monitor in order to benchmark aspects of physical activity for patients with thoracic cancer, explore how these relate to physician-rated performance status, and consider the implications for future studies. METHODS: Patients with thoracic cancer and an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2 wore an ActivPALTM monitor for 1 week. The mean time spent each day in a range of activities, e.g. standing or stepping, or their frequency, e.g. number of sit-to-stand transitions, steps taken, were calculated and compared according to ECOG PS. RESULTS: Data from 84 patients (54 male; mean (SD) age, 66 (9) years) were collated. Each day, patients spent a mean (SD) of 4.3 (2.0) h upright, completed 45 (17) sit-to-stand transitions and took 4,246 (2,983) steps. There was wide variation in each activity examined. All but the number of sit-to-stand transitions differed significantly between ECOG PS categories. CONCLUSIONS: These data provide a detailed insight into how physical activity levels decline across the range of ECOG PS categories studied. The wide variation in physical activity within each ECOG PS category suggests that this scale may lack sufficient sensitivity to evaluate new cachexia treatments. Our data help to inform future work in this area. PMID- 22311376 TI - Effect of nutritional supplementation upon pregnancy rates of goats under semiarid rangelands and exposed to the male effect. AB - The aim of this study was to evaluate possible effects of improved protein and energy diet upon reproductive outcomes of adult goats under marginal rangeland grazing conditions and exposed to the male effect during the anoestrous-dry season. Adult goats (Nubian * Criollo, nonpregnant, nonlactating, n = 160, 22 degrees 50' N, 100 degrees 59' W, 1,653 m) were randomly divided in two experimental groups: Control (CG; n = 80) and Supplemented (SG; n = 80). Both CG and SG goats were kept together during the day for ranging a semiarid rangeland while separated accordingly at night. SG goats were individually supplemented [400 g kg(-1) day(-1); 14% CP and 2.92 Mcal DE kg(-1)] during a 30-day period. Thereafter, both the CG [35.5 +/- 0.94 kg LW, 1.95 +/- 0.06 U, body condition score (BCS)] and the SG [39.5 +/- 0.94 kg LW, 2.29 +/- 0.06 BCS] were exposed to adult males (Nubian, n = 4, two per group) of proven libido and fertility and kept together at night (1700-0900) during a 42-day experimental breeding period. At the beginning of the breeding period, both LW (P < 0.001) and BCS (P < 0.001) were higher in the SG, which was also reflected in higher pregnancy rate (92.5 vs. 76.3%, P < 0.01). Nonetheless, both CG and SG depicted an increased abortion rate (52.5 vs. 41.9% P > 0.05), respectively. Results suggest that nutritional supplementation and the male effect were able to successfully invoke neurophysiological pathways to increase ovarian activity and to promote a uterine milieu prone to the establishment of pregnancy during the anoestrus season. However, the increased abortion rates observed in the study occurred irrespective of the nutritional regime offered during the premating stage. Therefore, there is a need to align the last third of gestation to the onset of the grazing season in order to increase reproductive and economic efficiency in those rangeland-based marginal goat production systems. PMID- 22311377 TI - Immunohistochemical expression of p16, p21, p27 and cyclin D1 in oral nevi and melanoma. AB - The acquisition of abnormalities at G1/S is considered a crucial step in the genesis and progression of melanoma. The expression of cell cycle regulators has also been used in various neoplasms as an adjunct to diagnosis. The aim of this study was to compare the expression of p16, p21, p27 and cyclin D1 in oral nevi and melanomas. Expression of these cell cycle regulatory proteins was evaluated by immunohistochemistry in 51 oral melanocytic lesions, including 38 intramucosal nevi and 13 primary oral melanomas. p16 and p27 were highly expressed in intramucosal nevi, whereas p21 and cyclin D1 expression was higher in oral melanomas. The results indicate that p21 and cyclin D1 may be involved in the development of oral melanomas, and eventually they may be useful in the differential diagnoses of oral benign and malignant melanocytic lesions. PMID- 22311378 TI - The acute effects of kava and oxazepam on anxiety, mood, neurocognition; and genetic correlates: a randomized, placebo-controlled, double-blind study. AB - RATIONALE: Kava (Piper methysticum) is a psychotropic plant medicine with history of cultural and medicinal use. We conducted a study comparing the acute neurocognitive, anxiolytic, and thymoleptic effects of a medicinal dose of kava to a benzodiazepine and explored for the first time specific genetic polymorphisms, which may affect the psychotropic activity of phytomedicines or benzodiazepines. METHODS: Twenty-two moderately anxious adults aged between 18 and 65 years were randomized to receive an acute dose of kava (180 mg of kavalactones), oxazepam (30 mg), and placebo 1 week apart in a crossover design trial. RESULTS: After exposure to cognitive tasks, a significant interaction was revealed between conditions on State-Trait Anxiety Inventory-State anxiety (p = 0.046, partial n2 = 0.14). In the oxazepam condition, there was a significant reduction in anxiety (p = 0.035), whereas there was no change in anxiety in the kava condition, and there was an increase in anxiety in the placebo condition. An increase in Bond-Lader "calmness" (p = 0.002) also occurred for the oxazepam condition. Kava was found to have no negative effect on cognition, whereas a reduction in alertness (p < 0.001) occurred in the oxazepam condition. Genetic analyses provide tentative evidence that noradrenaline (SLC6A2) transporter polymorphisms may have an effect on response to kava. CONCLUSION: Acute "medicinal level" doses of this particular kava cultivar in naive users do not provide anxiolytic activity, although the phytomedicine also appears to have no negative effects on cognition. PMID- 22311379 TI - Sex differences in offending trajectories in a Swedish cohort. AB - BACKGROUND: Despite the increased interest in female offending trajectories over the last decades, knowledge is still limited. AIM: To meet the need for more knowledge on female offending trajectories by studying sex differences in criminal career patterns. METHOD: Data on 518 female and 2567 male offenders up to age 30 from the Swedish longitudinal Project Metropolitan study were analysed using latent class analysis. RESULTS: The female offenders were much less predisposed to offend than the males, but when they did, they tended to follow a similar set of trajectories to males in their criminal development over time. Four criminal career patterns were identified for each sex. Two patterns were the same between the sexes, and two were gender unique. All career patterns had meaningful and distinct associations with crime characteristics. CONCLUSIONS: Our study presents indicators relating both to gender differences and to heterogeneity within the group of female offenders. One important finding was the identification of an adult-onset offender group unique to females. This group was characterised by high criminal activity over the years following their late onset. Further research will focus on the childhood origins, pathways and outcomes of different female antisocial and criminal careers. PMID- 22311380 TI - New perspectives in melatonin uses. AB - This review summarizes the metabolism, secretion, regulation and sites of action of melatonin. An updated description of the melatonin receptors, including their signal transduction mechanisms, distribution and characterization of receptor genes, is given. Special emphasis is focused on the clinical aspects and potential uses of melatonin in the sleep-wake rhythms, in the immune function, in cancer therapy, in neuroprotection against oxidative damage and antioxidant activities in different tissues. Finally, combined effects of melatonin with other drugs are discussed. PMID- 22311381 TI - Non-opioid IV adjuvants in the perioperative period: pharmacological and clinical aspects of ketamine and gabapentinoids. AB - Untreated acute postoperative pain can transform into chronic pain that may have major negative effects on the individual's quality of life. It can also prolong recovery, rehabilitation and length of hospital stay, thus affecting societal economic burden. Given the multiplicity of mechanisms involved in postoperative pain, a multimodal analgesia regimen, using a combination of opioids and multiple agents aiming to augment their effects via different routes of administration, is a pharmacologically appropriate approach. This polypharmacological application provides superior pain relief at rest and after movement, reduced opioid consumption associated with reduced analgesic-related adverse effects, and better chances to prevent the induction of later hyperalgesia. The most important adjuncts currently employed are ketamine and gabapentinoids. They have been shown to help in reaching the desired effect when administered at drug-specific modes and at proven effective dosing throughout the perioperative period. PMID- 22311382 TI - Memantine, an NMDA receptor antagonist, differentially influences Go/No-Go performance and fMRI activity in individuals with and without a family history of alcoholism. AB - RATIONALE: Individuals with a family history of alcoholism (family history positive [FHP]) show higher alcoholism rates and are more impulsive than those without such a family history (family history negative [FHN]), possibly due to altered N-methyl-D-aspartate (NMDA) receptor function. OBJECTIVES: We investigated whether memantine, an NMDA receptor antagonist, differentially influences impulsivity measures and Go/No-Go behavior and fMRI activity in matched FHP and FHN individuals. METHODS: On separate days, participants received a single dose of 40 mg memantine or identical-appearing placebo. RESULTS: No group performance differences were observed on placebo for Go correct hit or No Go false alarm reaction time on the Go/No-Go task. During fMRI, right cingulate activation differed for FHP vs. FHN subjects during No-Go correct rejects. Memantine had attenuated effects in FHP vs. FHN subjects: For No-Go false alarms, memantine was associated with limited reduction in subcortical, cingulate, and temporal regions in FHP subjects and reduced activity in fronto-striatal-parietal networks in FHN subjects. For No-Go correct rejects, memantine (relative to placebo) reduced activity in left cingulate and caudate in FHP but not FHN subjects. CONCLUSIONS: Lower sensitivity to the effects of memantine in FHP subjects is consistent with greater NMDA receptor function in this group. PMID- 22311383 TI - Anhedonia predicts altered processing of happy faces in abstinent cigarette smokers. AB - RATIONALE: Anhedonia-diminished capacity to experience pleasure-is associated with tobacco dependence and smoking cessation failure. However, the mechanisms linking anhedonia and smoking are unclear. OBJECTIVES: This study examined whether trait anhedonia predicted cognitive processing of emotional faces during experimentally manipulated acute tobacco deprivation in smokers. Because nicotine may offset reward processing deficits in anhedonia and these deficits may become expressed during abstinence, we hypothesized that anhedonia would predict diminished cognitive processing of happy (versus neutral) facial expressions in nicotine deprived, but not nondeprived states. METHODS: Smokers not attempting to quit (n = 75, 10+ cig/day) completed anhedonia questionnaires in a baseline session. Participants then attended two counterbalanced experimental sessions: one following 18-h of tobacco abstinence and one after unrestricted smoking. At both sessions, they completed a computer-based measure of attentional interference induced by emotional facial expressions. RESULTS: The extent to which anhedonia predicted attentional interference induced by happy faces differed as a function of deprivation status (ps <= .04, eta (p) (2) s > .06). Anhedonia predicted lower interference by happy (versus neutral) faces in the deprived condition (r = -.28, p = .02), but not in the nondeprived condition (r = .08, p = .51). Analyses of a secondary measure of anhedonia found marginally significant effects in the same direction. CONCLUSIONS: These findings indicate that disrupted processing of positively valenced social cues occurs upon abstinence in high-anhedonia individuals. This alteration may motivate reinstatement of smoking in order to remediate these deficits. More broadly, these results suggest that the neuropharmacological pathways affected by nicotine may underlie disrupted emotional processing in anhedonia-a prominent feature in several psychiatric disorders. PMID- 22311384 TI - Behavioral inhibition in mice bred for high vs. low levels of methamphetamine consumption or sensitization. AB - RATIONALE: Research indicates that genetics influence methamphetamine self administration as well as sensitization to the psychomotor-stimulating effects of methamphetamine (MA). Other studies have suggested that heightened levels of impulsivity, including low levels of behavioral inhibition, are associated with the use of drugs, including MA. OBJECTIVES: The current study examined whether lines of mice selected for traits associated with a heightened risk of developing MA dependence would also exhibit low levels of drug-naive inhibition and whether administration of MA would result in different levels of inhibition in animals selected to consume or respond more to MA. METHODS: A go/no-go task was used to assess inhibition in male and female mice selected for low or high levels of MA consumption or selected for high or low levels of locomotor sensitization to repeated injections of MA. RESULTS: Mice selected for MA sensitization differed in false alarms, precue response rates (measures of behavioral inhibition), and also hits (measure of operant responding). Mice selected for MA consumption did not differ in measures of behavioral inhibition, though hits differed. When MA was administered prior to the task, false alarms, precue response rates, and hits decreased for mice from all selected lines. Female high drinking mice were particularly resistant to MA's effects on hits, but not precue response rate or false alarms. CONCLUSIONS: These data suggest a shared, but complex, genetic association between inhibition processes, general levels of operant responding, and MA sensitization or consumption. PMID- 22311385 TI - A clinical case study of a Wolfram syndrome-affected family: pattern-reversal visual evoked potentials and electroretinography analysis. AB - Wolfram syndrome (WFS), or DIDMOAD, is a rare (1/100 000 to 1/770 000), progressive neurodegenerative disorder. In its early stages, it is characterized by insulin-dependent diabetes mellitus, optic atrophy and loss of sensorineural hearing-this is followed by diabetes insipidus, progressive neurological abnormalities and other endocrine abnormalities, which occur in later years. The aim of this study was to report on the clinical and electrophysiological findings from a family with the WFS1 mutation. The five family members were subjected to a complete ophthalmic examination, which included a flash full-field electroretinogram and pattern-reversal visual evoked potentials (PVEPs) performed according to ISCEV standards. Optic atrophy was confirmed in two homozygotic patients, where P100 latencies were significantly delayed-up to 146 ms in PVEP. P100 latencies were normal in the three heterozygotic patients we examined. Curve morphology abnormalities were observed in all five patients we examined. No literature describing the morphology of PVEP in Wolfram syndrome patients was found. In flash electroretinography, scotopic and photopic responses appeared in normal morphology and value. Diabetic retinopathy was not observed in the diabetes mellitus patients. PMID- 22311386 TI - Utility of the transition zone index for identification of prostate cancer in Chinese men with intermediate PSA levels. AB - PURPOSE: We aimed to investigate the utility of the transition zone index (TZI) for identification of prostate cancer (PCa) in Chinese men with prostate-specific antigen (PSA) levels of 4-10 ng/mL. METHODS: In this retrospective cohort study, results of transrectal ultrasonography (TRUS)-guided biopsy were assessed in 616 consecutive Chinese men; all subjects had intermediate serum PSA levels and normal digital rectal examination findings. The prostate and transition zone volumes were determined by TRUS. A TZI cutoff value of 0.47 produced the best sensitivity and specificity rates in receiver operating characteristic (ROC) curve analysis and thus was used to classify the study subjects into two subgroups: group 1 with TZI <= 0.47 and group 2 with TZI > 0.47. Logistic regression analysis was used to predict outcomes. The variables that were statistically significant in the stepwise logistic regression analysis were assessed using the ROC curve and the area under the curve. RESULTS: Overall, 166 of the 616 patients (26.9%) had histologically confirmed PCa. A total of 238 (38.6%) patients were classified into group 1, of whom 97 (40.8%) exhibited a positive biopsy; and 378 (61.4%) patients were classified into group 2, of whom 69 (18.3%) exhibited a positive biopsy. The stepwise logistic regression analysis revealed that PSA density (PSAD) exhibited the strongest predictive value in the overall population and in group 1, whereas PSA transition zone density (PSATZD) was the optimal predictor in group 2. The ROC curve analysis revealed that when using the TZI-specific 100% sensitivity cutoffs, 17.7% and 25% of the biopsies were unnecessary and could be avoided in the overall patient population prior to and following the division into groups, respectively (P = 0.002). Using an individually generated 95% sensitivity cutoff of 0.12 ng/mL(2) for PSAD and a cutoff of 0.179 ng/mL(2) for PSATZD for TZI-stratified cohorts of TZI <= 0.47 and TZI > 0.47, a more consistent specificity of 44% and 46.9%, respectively, for each cohort was observed. CONCLUSIONS: The optimal predictor for PCa differs between various TZI levels. The combination of PSAD in patients with TZI <= 0.47 and PSATZD in patients with TZI > 0.47 helps to identify potentially unnecessary biopsies compared to the use of a single PSAD for the entire patient population. The discrepancies regarding an optimal predictor in published reports are most likely due to the differing TZI levels among the cases. In this study, we demonstrated improved identification of PCa using TZI-adjusted cutoffs for PSAD and PSATZD. PMID- 22311387 TI - Troponin I as a prognostic marker of cardiac events in asymptomatic hemodialysis patients using a sensitive troponin I assay. AB - Elevated troponin T is known to be a prognostic marker for long-term cardiac events and mortality in asymptomatic end-stage renal disease patients. There are conflicting data in this regard with respect to troponin I (TnI). We recently showed a high incidence of elevated TnI levels in asymptomatic hemodialysis (HD) patients using a new generation sensitive TnI assay. The aim of this pilot study was to explore the prognostic value of TnI, as measured with this new assay, as a marker for outcomes in HD patients over a 2-year follow-up period. Fifty-one asymptomatic HD patients were enrolled, and pre-dialysis TnI levels were checked once monthly over 3 consecutive months. Patients were considered to be in the TnI positive group if TnI level on any of the three draws was >=0.035 ng/ml. All patients were followed for a period of 2 years. The primary end points were acute coronary syndrome, coronary revascularization, sudden death, or cardiac arrest. The secondary end point was all-cause mortality. Elevated TnI levels were found in 51% (26/51) of patients in our cohort. One TnI positive patient was subsequently lost to follow up. There were 6 cardiac events over 2 years, all of which were in the troponin positive group (6/25 or 24%). The presence of a positive TnI at baseline was significantly associated with future cardiac events (p=0.022). A prior history of coronary artery disease (CAD) was also significantly related to future cardiac events (p=0.010). No patient with negative TnI at baseline developed a cardiac event, while 45.5% of those with both a positive TnI and a history of CAD had an event. Fourteen deaths occurred over 2 years, 8 in TnI positive and 6 in the negative group. All-cause mortality was not associated with elevated TnI levels at baseline. We found a significant association between positive TnI and subsequent cardiac events in asymptomatic HD patients followed for 2 years. TnI levels, as measured with a sensitive assay, may be useful in assessing cardiac risk in asymptomatic HD patients. This needs further confirmation in a larger cohort. PMID- 22311388 TI - First dose in children: physiological insights into pharmacokinetic scaling approaches and their implications in paediatric drug development. AB - Dose selection for "first in children" trials often relies on scaling of the pharmacokinetics from adults to children. Commonly used approaches are physiologically-based pharmacokinetic modeling (PBPK) and allometric scaling (AS) in combination with maturation of clearance for early life. In this investigation, a comparison of the two approaches was performed to provide insight into the physiological meaning of AS maturation functions and their interchangeability. The analysis focused on the AS maturation functions established using paracetamol and morphine paediatric data after intravenous administration. First, the estimated AS maturation functions were compared with the maturation functions of the liver enzymes as used in the PBPK models. Second, absolute clearance predictions using AS in combination with maturation functions were compared to PBPK predictions for hypothetical drugs with different pharmacokinetic properties. The results of this investigation showed that AS maturation functions do not solely represent ontogeny of enzyme activity, but aggregate multiple pharmacokinetic properties, as for example extraction ratio and lipophilicity (log P). Especially in children younger than 1 year, predictions using AS in combination with maturation functions and PBPK were not interchangeable. This highlights the necessity of investigating methodological uncertainty to allow a proper estimation of the "first dose in children" and assessment of its risk and benefits. PMID- 22311389 TI - Correlation of apparent diffusion coefficient measured by diffusion-weighted MRI and clinicopathologic features in pancreatic cancer patients. AB - BACKGROUND/PURPOSE: The aim of this study was to evaluate the clinical usefulness of diffusion-weighted magnetic resonance imaging (DWI) in patients with pancreatic cancer by comparing the apparent diffusion coefficient (ADC) value with clinicopathologic features. METHODS: Twenty-two consecutive patients (12 men, 10 women; mean age 64.4 years) with pancreatic cancer underwent DWI before surgery. We retrospectively investigated the correlations between tumor ADC value and clinicopathologic features. RESULTS: Apparent diffusion coefficient value was significantly lower for pancreatic cancer than for noncancerous tissue (P < 0.001). Receiver operating characteristic analysis yielded an optimal ADC cutoff value of 1.21 * 10(-3) mm(2)/s to distinguish pancreatic cancer from noncancerous tissue. There was a significant negative correlation between ADC value and tumor size (r = -0.59, P = 0.004) and between ADC value and number of metastatic lymph nodes (r = -0.56, P = 0.007). Tumors with low ADC value had a significant tendency to show high portal venous system invasion (P = 0.02) and extrapancreatic nerve plexus invasion (P = 0.01). CONCLUSIONS: Apparent diffusion coefficient value appears to be a promising parameter for detecting pancreatic cancer and evaluating the degree of malignancy of pancreatic cancer. PMID- 22311391 TI - [Rehabilitation and business]. PMID- 22311390 TI - Complete mitochondrial genomes of two cockroaches, Blattella germanica and Periplaneta americana, and the phylogenetic position of termites. AB - The mitochondrial genomes are one of the most information-rich markers in phylogenetics. The relationships within superorder Dictyoptera have been debated in the literature. However, the closely related termites (Isoptera) are retained as unranked taxon within the order Blattaria (cockroaches). In this work, we sequenced the complete mitogenomes of two cockroaches, reconstructed the molecular phylogeny and attempted to infer the phylogenetic position of termites in Blattaria more reliably. The complete mtDNA nucleotide sequences of the peridomestic American cockroach (Periplaneta americana L.) and the domestic German cockroach (Blattella germanica L.) are 15,025 and 15,584 bp in size, respectively. The genome shares the gene order and orientation with previously known Blattaria mitogenomes. Most tRNAs could be folded into the typical cloverleaf secondary structure, but the tRNA-Ser (AGN) of P. americana appears to be missing the dihydrouridine arm. Using nucleotide and amino acid sequences as phylogenetic markers, we proposed that termites should be treated as a superfamily (Termitoidea) of cockroaches. We suggested that Polyphagoidea was the sister group of Termitoidea in Blattaria and supported that the suborder Caelifera is more closely related to the Phasmatodea than to the suborder Ensifera of Orthoptera. PMID- 22311392 TI - [Company health promotion as a possible preparatory stage of effective rehabilitation]. AB - In Section 20a of Book 5 of the German Social Code (SGB V), the legislator obliged the health insurance funds to carry out company health promotion in cooperation with the accident insurance agency in charge. He thus created a foundation for more health and secure earnings or employment potential in the companies. At the same time company health promotion permits detecting threats to this potential. That helps to identify a possible need for rehabilitation at an earlier stage and to take appropriate action.To verify whether and how this instrument of preventive health policy is being used, an empirical study explored the actual application of that legal provision in small and medium-sized enterprises in particular. The law, administrative measures and company everyday evidence were set against each other under legal and de facto aspects, which showed obvious deficits in applying the law. Proposals for better company health promotion are derived from these findings. In the first place, actors in administration and self-management of the statutory health and accident insurance schemes are addressed to this end, in anticipation of enhanced implementation. A premature reduction of earning capacity could thus be counteracted. Pension insurants could retain gainful employment for a longer time, companies would have a more reliable employee basis. Social insurance carriers, notably the health and pension insurance schemes, would have to spend less in the end. A development like that would be a benefit for all--including the state. PMID- 22311393 TI - [Company integration management in small and medium-sized companies. Legal requirements and prerequisites for successful implementation]. AB - The article is based on the results of the project "Company integration management in small and medium-sized companies. Legal requirements and prerequisites for a successful implementation" (01 January 2009-31 August 2010). BACKGROUND: Since 2004 all employers have been legally bound to offer company integration management (BEM, Betriebliches Eingliederungsmanagement) for all employees who have been incapacitated for work for more than 6 weeks within a year (Section 84 SGB IX, Book 9 of the German Social Code). Objective of this law is to ensure ongoing employment. OBJECTIVE: The aim of the study was to investigate the requirements companies, rehabilitation centres and services as well as social insurance institutions are faced with according to Section 84 SGB IX. Prerequisites for an effective implementation of BEM in small and medium sized enterprises were analyzed. METHOD: Protocol-based interviews with experts were adopted. A total of 38 interviews with experts were carried out. The experts interviewed were either willing to give information by interest (concernment) or were named by law as an initiator or co-operator in the process of integration. A substantial literature research was performed in advance of the interviews. RESULTS: The awareness level of BEM is still very low even 7 years after its introduction. Small and medium-sized enterprises do not have any significant experiential knowledge of long-term incapacity for work and, hence, about BEM. Due to a lack of workers representation in many small and medium companies, management does not receive initiatives or support in implementation of BEM from employees' side. Employers prefer a central contact point providing them with the information and help needed, the common service units, however, being widely unknown in this context. Cost comparisons suggest that a company integration management might be more cost-effective than dismissing employees who are incapacitated for some fields of work. These findings might even hold true for small and medium-sized companies. Social insurance institutions are aware of company integration management; however there is a substantial lack of experience. There is some evidence that incentives and bonuses according to Section 84, 3 SGB IX would not have any significant impact on the implementation of company integration management in small and medium-sized enterprises. POLICY RECOMMENDATION: All relevant actors in the field of company integration management should reassess their possibilities to advocate integration management. Not only employees but also employers and social security institutions will benefit from comprehensive implementation of company integration management. PMID- 22311394 TI - [From health promotion to return to work--report from industrial medicine practice]. AB - Company doctors can assume an important moderator function in company health management because they know both the individual employee with his or her abilities and functional disorders as well as the individual workplace and its organizational framework conditions. Moreover, they have access to population groups who would not as a rule make use of health care services. In the framework of industrial medicine preventive examinations, consultations and workplace inspections, they can identify a need for rehabilitation at an early stage, can support applications for services and return to work, and thus contribute to greater sustainability. PMID- 22311395 TI - [Which services do companies need to retain employability in their workforce?- help offered by the German Pension Insurance]. AB - German Pension Insurance as a provider of services in rehabilitation has reacted to demographic changes in society, both strategic and practical. The implementation of services for companies including support of company return to work management and prevention services for employees with specific health related burdens offer the chance to identify an endangerment of earning capacity at an early stage. Workplace-orientated medical rehabilitation increases the focus on the job and the workplace in rehabilitation under the pension insurance scheme, both in selecting the right service for a client as well as in the service itself. Employers, employees and pension insurance together benefit from close cooperation. PMID- 22311396 TI - ["Vocational perspective"--short-term efficacy of a group treatment for patients with extensive work-related problems during medical rehabilitation]. AB - AIM OF THE STUDY: To analyze the short-term efficacy of the Vocational Perspective programme for patients identified as having extensive work-related problems during rheumatology or orthopaedic inpatient rehabilitation. The primary objectives of the programme on patient level are to convey information about the legal provisions regarding earning incapacity and occupational reintegration, to suggest strategies for dealing with one's own occupational situation, and to strengthen the motivation to stay employed. The programme is explicitly designed for patients who wish to retire or have applied for a pension. On the systemic level, the main goals are to facilitate doctor-patient communication and to increase rehabilitation teams' awareness of occupational problems. METHODS: In a controlled quasi-experimental design, 359 subjects were consecutively assigned to either the control group (CG, n=177) or the intervention group (IG, n=182). The control group received standard care only, whereas the intervention group additionally participated in the 5-part Vocational Perspective programme. Evaluation criteria were assessed by questionnaire at the beginning (t1) and at end of rehabilitation (t2). Survey participation was 92.2% at t2. The socio medically relevant knowledge status was objectively documented using a specially designed knowledge questionnaire. Aspects of treatment satisfaction were evaluated using individual items, and the subjective prognosis of gainful employment was assessed using the Subjective Prognosis of Gainful Employment (SPE) scale. Facilitation of communication between doctor and patient was operationalized at patient level in terms of patient satisfaction with medical care, and increased awareness of the rehabilitation team was operationalized in terms of the rate of recommendations to apply for vocational reintegration (LTA) services at discharge. Emotional and functional parameters were exploratively analyzed (anxiety and depression using the IRES 3.1 scales, and subjectively experienced pain-related impairment using the Pain Disability Index). RESULTS: Scores for subjective satisfaction with job-related information, medical care, socio-medical assessment, and the overall benefits of rehabilitation were significantly higher in the intervention group than in the control group. IG subjects moreover were better able to use the rehabilitation measure to clarify their occupational situation and exhibited significantly greater improvement of socio-medically relevant knowledge. Age proved to be an important predictor of change in a patient's subjective prognosis for gainful employment (SPE): A positive change in SPE was observed in both groups in subjects under 50, in those aged 50 and older, however, only in the intervention group. No differences between the two groups were observed in terms of functional and emotional parameters (e. g., disability through pain, anxiety, and depression). A total of 60% of the subjects received a recommendation at discharge to apply for vocational reintegration services, the proportion however was significantly higher in the IG. CONCLUSIONS: The Vocational Perspective programme met the patients' high demand for information on relevant socio-medical facilities and services regarding career change and facilitated communication between the doctor and patient by creating greater transparency. The improvement of subjective prognosis for gainful employment observed in the subgroup of older patients indicates that specialized interventions are needed in precisely this disadvantaged group in order to improve their own vocational expectations and thus to improve their chances of reintegration into work life. The high rate of recommendations to apply for vocational reintegration services suggests that rehabilitation teams already have a high awareness of job-related problems even under "usual care" conditions. PMID- 22311397 TI - [Social security agencies support of company integration management and stepwise return to work--experiences of the integration agency]. PMID- 22311398 TI - [Works council participation in the framework of company integration management]. PMID- 22311399 TI - [Expert meeting on patient education Oct. 21 to 22, 2011 in Erkner]. PMID- 22311400 TI - [Rehabilitation as a bridge between medical care and vocational integration- results of the 12th GfR-SAT-BBS-Symposium, Nov. 11, 2011 in Jena University Hospital]. PMID- 22311401 TI - Non-viral environmental risk factors for nasopharyngeal carcinoma: a systematic review. AB - This review aims to systematically summarize the epidemiological studies on nasopharyngeal carcinoma (NPC) conducted over the past half century, covering descriptive epidemiological studies and reports on non-viral risk factors. Multiple lines of epidemiologic evidence for established risk factors are systematically presented in comprehensive tables. The potential interactions among environmental factors and genetic components, and also the impacts of parallel sequencing technology on the aetiology of NPC are discussed. Finally, we propose a modified model for the pathogenesis of nasopharyngeal carcinoma based on the current knowledge. PMID- 22311402 TI - Cancer biology and the nuclear envelope: a convoluted relationship. AB - Although its properties have long been used for both typing and prognosis of various tumors, the nuclear envelope (NE) itself and its potential roles in tumorigenesis are only beginning to be understood. Historically viewed as merely a protective barrier, the nuclear envelope is now linked to a wide range of functions. Nuclear membrane proteins connect the nucleus to the cytoskeleton on one side and to chromatin on the other. Several newly identified nuclear envelope functions associated with these connections intersect with cancer pathways. For example, the nuclear envelope could affect genome stability by tethering chromatin. Some nuclear envelope proteins affect cell cycle regulation by directly binding to the master regulator pRb, others by interacting with TGF-beta and Smad signaling cascades, and others by affecting the mitotic spindle. Finally, the NE directly affects cytoskeletal organization and can also influence cell migration in metastasis. In this review we discuss the link between the nuclear envelope and cellular defects that are common in cancer cells, and we show that NE proteins are often aberrantly expressed in tumors. The NE represents a potential reservoir of diagnostic and prognostic markers in cancer. PMID- 22311403 TI - Clinically relevant drug interactions in anxiety disorders. AB - OBJECTIVE: Certain drugs used in the treatment of patients with anxiety disorders can interact with other psychotropic drugs and with pharmacological treatments for physical illnesses. There is a need for an updated comparative review of clinically relevant drug interactions in this area. DESIGN: Relevant literature on drug interactions with medications used in the treatment of anxiety disorders was identified through a search in MEDLINE and EMBASE. RESULTS: Drug interactions involving medications used to treat anxiety disorders may be pharmacokinetic, such as enzyme inhibition or induction in the cytochrome P450 system and transporter-mediated drug interactions, or pharmacodynamic, such as additive effects in causing drowsiness or additive effects at neurotransmitter receptors. Certain selective serotonin reuptake inhibitors (fluoxetine, fluvoxamine, and paroxetine) are particularly liable to be potentially involved in untoward pharmacokinetic interactions. CONCLUSIONS: The potential for drug interactions with medications used in anxiety disorders should be the cause of clinical concern, particularly in elderly individuals. However, the liability for harmful drug interactions may be anticipated, and the risk reduced. Although not all interactions are clinically relevant, careful monitoring of clinical response and possible interactions is essential. PMID- 22311404 TI - Atherosclerosis, vascular aging and therapeutic strategies. AB - With the arrival of the era of global population aging, we strive for healthy aging and a healthy senior life rather than simple prolongation of the physical age. For the past 50 years, cardiovascular diseases (CVD) have been the most common cause of death among the elderly people globally. In China, there has been an exponential increase in the incidence of heart disease and stroke in the elderly population. Atherosclerosis is the pathological change in the coronary artery disease, stroke, and peripheral vascular disease. Despite the significant benefit demonstrated, control of classic risk factors alone, such as lifestyle change or drug therapy, was shown to have limitations in reducing the incidence of cardiovascular events. Vascular aging has been shown to be an important independent predictor of CVD events. Interventions targeting vascular aging have emerged as a new paradigm in conjunction with control of risk factors for the prevention of CVD. Vascular aging and atherosclerosis are two distinct pathological changes and difficult to distinguish clinically. Recent research with Chinese medicine (CM) has shown encouraging observations, linking the clinical benefit of delaying vascular aging and treating atherosclerosis. These results demonstrate great potential of CM in the prevention and treatment of CVD. PMID- 22311405 TI - Clinical study on treatment of infantile cytomegalovirus hepatitis with integrated Chinese and Western medicine. AB - OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine (CM) in treating infantile cytomegalovirus hepatitis (ICH). METHODS: A total of 100 infant ICH patients were randomly assigned to two groups, 60 in the treatment group and 40 in the control group. Ganciclovir was administered to all patients via intravenous dripping at dose of 5 mg/kg every 12 h for 2 weeks, followed by 5 mg/kg once a day for 5 days every week; the whole treatment course lasted 8 weeks. Besides, the patients in the treatment group were treated with CM of Qinggan Lidan Decoction (, QLD) during icteric stage, and Yigan Jiangmei Decoction (, YJD) in non-icteric hyper-aminotransferase stage by oral medication, while for those in the control group, glucurolactone 50 mg was given three times per day. The efficacy of treatment was evaluated at the ends of 2nd, 4th and 8th weeks, respectively. And a follow-up study was carried out for 6-24 months. RESULTS: The total effective rate was 95.0% (57/60) in the treatment group and 77.5% (31/40) in the control group; the overall curative effect in the former was superior to that in the later, showing a significant difference (P=0.021). Cholestasis and liver function were improved in both groups, and the effect of reducing serum bilirubin level in the treatment group was more rapid and extensive than that in the control group, which could reduce the post-hepatitis cirrhotic risk caused by long-term cholestasis and liver cell damage. CONCLUSION: The therapeutic efficacy of integrated CM and Western medical drug therapy, by using QLD during icteric stage and YJD in nonicteric hyper-aminotransferase stage, was significantly higher than that of routine Western medical treatment alone; it was an ideal project for the treatment of infantile cytomegalovirus hepatitis. PMID- 22311406 TI - Effect of Feitai Capsule () on quality of life and progression-free survival of patients with unresectable non-small cell lung cancer. AB - OBJECTIVE: To examine the effect of a Chinese medicinal herbal formula (Feitai Capsule, ) on the quality of life (QOL) and progression-free survival (PFS) of patients with unresectable non-small cell lung cancer (NSCLC). METHODS: Sixty-two patients were randomly divided into the treatment group (31 cases) and the control group (31 cases). For the treatment group, 4 capsules (1.2 g/capsule) of Feitai Capsule were administered 3 times a day after meals for 3 weeks; then no drug was administered for 1 week. This schedule was continued for at least 3 more cycles (12 weeks totally). If there were no obvious toxic reactions, the treatment was extended. The patients were evaluated at least once every 8 weeks until progressive disease (PD). For the control group, the regular follow-up and evaluation were performed at least once every 8 weeks until PD. Clinical symptoms, objective response, physical constitution and energy, QOL, and PFS were evaluated regularly. Analysis of variance (ANOVA), a non-parametric test, and analysis of covariance were used to compare clinical features, amelioration of clinical symptoms, physical constitution and energy, and QOL. Kaplan-Meier analysis was used to compare the two-group PFS. RESULTS: Sixty patients finished the final evaluation, with 30 patients in each group. Baseline characters between groups were not significantly different (P>0.05). The control group had a 36.7% improvement in clinical symptoms, while the treatment group had a 73.3% improvement. This difference was statistically significant (Z= -2.632, P=0.008). The control group had a 26.7% improvement in the Karnofsky performance status (KPS), while the treatment group had a 53.4% improvement. This was also significantly different (Z=-2.182, P=0.029). A comparative analysis indicated a positive correlation (r=0.917, P<0.001). Compared with the control group, QOL in the treatment group was significantly improved, except in the social/family condition and doctor-patient relationship indicators. The PFS of the treatment group and control group were 6.23 months and 4.67 months, respectively (P=0.048). CONCLUSION: Feitai Capsule, a Chinese medicinal herbal treatment could improve the QOL and extend the PFS of the unresectable NSCLC patients. PMID- 22311407 TI - Development of clinical practice guidelines in 11 common diseases with Chinese medicine interventions in China. AB - OBJECTIVE: To analyze the clinical practice guideline (CPG) development on 11 common diseases with Chinese medicine (CM) interventions in China. METHODS: The CPGs of 11 common diseases which could be treated effectively with CM had been published between 1980 and 2010 in China. The 11 diseases include coronary heart disease (angina pectoris), hypertension, chronic gastritis, rheumatoid arthritis, cerebral infarction, migraine, diabetes, primary osteoporosis, insomnia, common cold, and IgA nephropathy. The issuing organization, date of publication, development methods, and citation rate of the CPGs were analyzed. According to the development method, each guideline was categorized as consensus-based (CB), evidence-based (EB), or consensus based with no explicit consideration of evidence-based (CB-EB). RESULTS: Thirty-three CPGs on the 11 common diseases were found: 20 guidelines were classified as CB, 13 as CB-EB and none as EB. Fifteen CPGs were issued by the China Association of Chinese Medicine, 8 by professional working groups, and 4 by the State Administration of Traditional Chinese Medicine. Six guidelines were published between 1980 and 1990, 9 between 1991 and 2000, and 18 between 2001 and 2010. Fifty-eight percent of these guidelines have not been amended timely. Only 54.5% (18/33) of the 33 guidelines were cited by other researchers and 45.5% (15/33) percent had never been cited. CONCLUSIONS: Most CPGs developed for 11 common diseases with CM approaches in China are consensus, and their citation rates are relatively low. The results suggest that more EB CPG or CPG strictly based on expert consensus could be developed, and great efforts should be made for future CM CPG application. PMID- 22311408 TI - Dingxin recipe ( ) prevents ischemia/reperfusion-induced arrhythmias via up regulating prohibitin and suppressing inflammatory responses. AB - OBJECTIVE: To identify the underlying mechanisms of the protective effects of Dingxin Recipe (: , DXR), a Chinese compound prescription that has been used clinically in China for more than 20 years, on ischemia/reperfusion (I/R)-induced arrhythmias in rat model. METHODS: A total of 30 rats were randomly divided into three groups: sham group, I/R group, and DXR-pretreated I/R (DXR-I/R) group. Rats in the DXR-DXRI/R group were intragastrically administrated with DXR (12.5 g/kg per day) for consecutive 7 days, while rats I/in the sham and I/R groups were administrated with normal saline. Arrhythmias were introduced by I/R and electrocardiograms (ECG) were recorded. Two-dimensional (2-D) polyacrylamide gel electrophoresis and matrix-matrix assisted laser desorption ionization time-of flight mass spectrometry (MALDI-TOF MS) were used to identify assisted differentially expressed proteins. Immunohistochemistry, real-time quantitative polymerase chain reaction (RQ-RQPCR), Western blot, and enzyme-linked immunosorbent assay (ELISA) were performed to analyze proteins PCR), obtained in the above experiments. RESULTS: DXR significantly reduced the incidence and mean duration of ventricular tachycardia and ventricular fibrillation and dramatically decreased the mortality, as well as arrhythmia score, compared with those of the I/R group. Among successfully identified proteins, prohibitin (PHB) and heart fatty acid binding protein (hFABP) were up-regulated in DXR-pretreated I/R rats compared with those of the I/R rats. In addition, compared with the I/R group, the level of glutathione (GSH) was elevated accompanied by reduced expressions of interleukin-6 (IL-6) and neutrophil infiltration in I/R rats with DXR pretreatment. CONCLUSIONS: DXR could alleviate I/R-induced arrhythmias, which might be related to increased expression of PHB. The enhanced expression of PHB prevented against the depletion of GSH and consequently inhibited apoptosis of cardiomyocytes. Furthermore, up-regulation of PHB might ameliorate I/R-induced cell death and leakage of hFABP by suppressing neutrophil infiltration and IL-6 expressions. PMID- 22311409 TI - Electrical stimulation of deep peroneal nerve mimicking acupuncture inhibits the pressor response via capsaicin-insensitive afferents in anesthetized rats. AB - OBJECTIVE: To assess the inhibitory modulation of blood pressure by stimulation of the deep peroneal nerve (DPN) and to determine the involvement of nociceptive fibers in the modulation. METHODS: All the animals were divided into six groups (A-F). The rats in groups A and B received no pretreatment. The rats in groups C and D received subcutaneous injection of capsaicin or control vehicle, respectively, near the DPN for 2 days. Those in groups E and F had the DPN exposed to capsaicin or control vehicle, respectively, for 20 min. Subsequently, pressor responses were induced by stimulation of paraventricular nucleus (PVN) either electrically (groups A and C C-F) or chemically via injection of glutamate (group B). After two stable pressor responses (baseline), all groups were subject to 5-min DPN stimulation followed by PVN stimulation for 10 s. Arterial blood pressure, heart rate, and electrocardiogram were recorded. The pressor response was calculated as the difference in the mean arterial pressure (MAP) before and after PVN stimulation, and changes from baseline in pressor response after DPN stimulation were compared between the groups. RESULTS: Increases of MAP of 22.88+/-2.18 mm Hg and 20.32+/-5.25 mm Hg were induced by electrical (group A) or chemical (group B) stimulation of the PVN, respectively. These pressor responses were inhibited by stimulation of the DPN, and the MAP was reduced to 12.00+/-2.10 mm Hg in group A (n=6, P<0.01) and 7.00+/-2.85 mm Hg in group B (n=6, P<0.01). Subcutaneous injection of capsaicin (125 mg/kg) near the DPN in group C (n=7) had no effect on the inhibitory effect of DPN stimulation compared with the group D (n=9), and neither did blockade of nociceptive fibers with capsaicin in group E (n=6) compared with group F (n=8). CONCLUSION: Stimulation of the DPN mimicking acupuncture has an inhibitory effect on the pressor response, and the effect is mediated by capsaicin-insensitive afferent fibers in the DPN. PMID- 22311410 TI - Xiaoyin recipe ( ) for psoriasis induces a Th1/Th2 balance drift toward Th2 in peripheral blood mononuclear cells of experimental autoimmune thyroiditis rats. AB - OBJECTIVE: To explore the regulatory mechanism of Xiaoyin Recipe () on the T helper 1/T helper 2 (Th1/Th2) immune balance. METHODS: Thirty-six experimental animals were divided into three groups, 12 rats in each group: blank control group (B group), negative control group (N group), and Xiaoyin Recipe treatment group (T group). The latter two groups received immunization of experimental autoimmune thyroiditis (EAT), and T group were treated with Xiaoyin Recipe for a month. Then, the expression of Th1-Th2-related genes in peripheral blood mononuclear cells (PBMCs) were screened with Oligo GEArray Rat Th1-Th2-Th3 Microarray. The expressions of tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), T-box expressed in T-cells (T-bet), and GATA-binding protein-3 (GATA-3) were detected by real-time polymerase chain reaction (RT-PCR). RESULTS: Gene array screening showed that compared to N group, in T group after Xiaoyin Recipe treatment, 3 genes were upregulated in EAT rats, including interleukin-27 receptor alpha (IL-27ralpha), glomulin (Glmn), and GATA-3, while 38 genes were downregulated, such as CD28, IL-18, signal transducer, and activator of transcription 1 (STAT1), T-bet, TNF receptor superfamily member 4 (TNFRSF4), TNF ligand superfamily member 5 (TNFSF5), and TNF receptor superfamily member 5 (TNFRSF5). While RT-PCR showed that there was an increased level of TNF alpha mRNA (P<0.01), an elevated ratio of T-bet/GATA-3, and a decreased level of IL-10 mRNA in PBMC of N and T group compared to B group (P <0.01); and after treatment with Xiaoyin Recipe, IL-10 mRNA level increased (P <0.01), while TNF alpha mRNA level and T-bet/GATA-3 ratio decreased in T group compared to N group (P <0.01). CONCLUSION: Xiaoyin Recipe for psoriasis could induce a Th1/Th2 balance drift toward Th2 in PBMC of EAT rats and thus improve the conditions. PMID- 22311411 TI - Effects of electroacupuncture combined psycho-intervention on cognitive function and event-related potentials P300 and mismatch negativity in patients with internet addiction. AB - OBJECTIVE: To observe the effects of comprehensive therapy (CT) with electroacupuncture (EA) in combination with psycho-intervention (PI) on the cognitive function and event-related potentials (ERP), P300 and mismatch negativity (MMN), in patients with internet addiction (IA) for a preliminary exploration of the possible mechanism of the therapy. METHODS: One hundred and twenty patients with IA were randomly divided into three groups, and a total of 112 subjects reached the final analysis of the trial, the EA group (39 patients), the PI group (36 patients) and the CT group (37 patients). EA was applied at acupoints Baihui (GV20), Sishencong (EX-HN1), Hegu (LI4), Neiguan (PC6), Taichong (LR3) and Sanyinjiao (SP6), once every other day; PI with the cognitionbehavior mode was implemented every 4 days; both EA and PI were used in the CT group. The treatment course for all patients was 40 days. Changes before and after treatment in terms of scoring by the IA self-rating scale, short-term memory capacity, short-term memory span, and the latency and amplitude of P300 and MMN in patients were observed. RESULTS: After treatment, in all groups, the IA score was lowered significantly (P <0.05) and scores of short-term memory capacity and short-term memory span increased significantly (P <0.05), while the decreased IA score in the CT group was more significant than that in the other two groups (P <0.05). ERP measurements showed that P300 latency was depressed and its amplitude raised in the EA group; MMN amplitude increased in the CT group (all P<0.05). CONCLUSION: The EA in combination with PI could improve the cognitive function of IA patients, and its mechanism might be related to the speedup of cerebral discrimination on external stimulus and the enhancement of effective resource mobilization during information processing of the brain. PMID- 22311412 TI - Chinese herbal medicine in the treatment of nonalcoholic fatty liver disease. AB - Chinese herbal medicine has developed new therapies for nonalcoholic fatty liver disease (NAFLD) based on its unique theory system and substantial herb remedies. In this review, 21 traditional Chinese herbs were introduced for their potential benefit in the treatment of NAFLD. Majority of them are evaluated by experimental studies and few by multicenter clinical trials. Herbal monomers as berberine and resveratrol, extracts from Polygonum hypoleucum Ohwi, and Artemisia sacrorum Ledeb., and formulae including Yinchenhao Decoction (, YCHD), Qushi Huayu Decoction (, QSHYD), and Danning Tablet () were discussed in detail on their therapeutic potentials. Most of these herbal medicines were proved to improve biochemical and histological changes of NAFLD both in vitro and in vivo. Also, their therapeutic activities were associated with inhibiting lipid accumulation through adenosine monophosphate-activated protein kinase activation or upregulating low-density lipoprotein receptor (LDLR) expression, alleviating lipid peroxidation, and reducing the production of inflammatory cytokines. Although the efficacy and safety of these herbal medicines needed to be evaluated in multicenter large-scale clinical trials, Chinese medicine is promising and effective for preventing and treating NAFLD disease. PMID- 22311413 TI - Relation between FDG uptake and apparent diffusion coefficients in glioma and malignant lymphoma. AB - OBJECTIVE: This study evaluates the relation between 2-deoxy-2-[18F]fluoro-D: glucose (FDG) uptake using positron emission tomography/CT and the apparent diffusion coefficient (ADC) in patients with glioma and malignant lymphoma. METHODS: For 36 patients (30 with glioma and 6 with malignant lymphoma), the standardized uptake value (SUV) ratio was calculated to assess the FDG uptake. Pearson's correlation analysis was used to assess the relation between the SUV ratio and the ADC value: those of low-grade glioma and high-grade glioma were compared, as were those of glioblastoma and malignant lymphoma. RESULTS: Inverse correlation between the SUV ratio and the minimum ADC was found for all cases (P < 0.0001, r = 0.68) and for glioma cases (P < 0.0001, r = 0.67). High-grade gliomas showed a significantly higher SUV ratio than low-grade gliomas did (P < 0.0001); they also showed significantly lower minimum ADC than low-grade gliomas did (P < 0.001). Cut-off values used for the SUV ratio of 0.9 and for the minimum ADC of 0.99 * 10(-3 )mm(2)/s were used to differentiate high-grade from low-grade gliomas, with high accuracy. Malignant lymphoma showed a significantly higher SUV ratio than glioblastoma (P < 0.0001). No significant difference in the ADC value was found between glioblastoma and malignant lymphoma (the minimum ADC: P = 0.13, the mean ADC: P = 0.084, respectively). CONCLUSIONS: An inverse correlation was found between the SUV ratio and the minimum ADC in glioma and malignant lymphoma. The SUV ratio and the minimum ADC are useful to evaluate the grading of gliomas. The SUV ratio might be more useful for differentiating malignant lymphoma from glioblastoma than the ADC value is. PMID- 22311414 TI - Usefulness of extent analysis for statistical parametric mapping with asymmetry index using inter-ictal FGD-PET in mesial temporal lobe epilepsy. AB - OBJECTIVE: Inter-ictal (18)F-2-fluoro-deoxy-D: -glucose-positron emission tomography (FDG-PET) is widely used for preoperative evaluation to identify epileptogenic zones in patients with temporal lobe epilepsy. In this study, we combined statistical parametric mapping (SPM) with the asymmetry index and volume of-interest (VOI) based extent analysis employing preoperative FDG-PET in unilateral mesial temporal lobe epilepsy (MTLE) patients. We also evaluated the detection utility of these techniques for automated identification of abnormalities in the unilateral hippocampal area later confirmed to be epileptogenic zones by surgical treatment and subsequent good seizure control. METHODS: FDG-PET scans of 17 patients (9 males, mean age 35 years, age range 16 60 years) were retrospectively analyzed. All patients had been preoperatively diagnosed with unilateral MTLE. The surgical outcomes of all patients were Engel class 1A or 1B with postoperative follow-up of 2 years. FDG-PET images were spatially normalized and smoothed. After two voxel-value adjustments, one employing the asymmetry index and the other global normalization, had been applied to the images separately, voxel-based statistical comparisons were performed with 20 controls. Peak analysis and extent analysis in the VOI in the parahippocampal gyrus were conducted for SPM. For the extent analysis, a receiver operating characteristic (ROC) curve was devised to calculate the area under the curve and to determine the optimal threshold of extent. RESULTS: The accuracy of the method employing the asymmetry index was better than that of the global normalization method for both the peak and the extent analysis. The ROC analysis results, for the extent analysis, yielded an area under the curve of 0.971, such that the accuracy and optimal extent threshold of judgment were 92 and 32.9%, respectively. CONCLUSION: Statistical z-score mapping with the asymmetry index was more sensitive for detecting regional glucose hypometabolism and more accurate for identifying the side harboring the epileptogenic zone using inter ictal FDG-PET in unilateral MTLE than z-score mapping with global normalization. Moreover, the automated determination of the side with the epileptogenic zone in unilateral MTLE showed improved accuracy when the combination of SPM with the asymmetry index and extent analysis was applied based on the VOI in the parahippocampal gyrus. PMID- 22311415 TI - Prognostic implications of microscopic involvement of surgical resection margin in patients with differentiated papillary thyroid cancer after high-dose radioactive iodine ablation. AB - OBJECTIVE: To evaluate the relationship between microscopic cancerous involvement of surgical margin and recurrence in patients with differentiated papillary thyroid cancer (PTC) who underwent total thyroidectomy followed by high-dose radioactive iodine ablation (HDRIA). METHODS: Consecutive 197 PTC patients (184 women; mean age 44.9 years) who underwent total thyroidectomy without gross residual tumor followed by HDRIA were retrospectively reviewed. Resection margin involvement was evaluated and recurrence of the disease was assessed with clinicopathologically. Recurrence detected within 12 months after HDRIA were defined as early recurrence, detected after 12 months were defined as late recurrence. RESULTS: The mean follow-up was 85.9 +/- 16.6 months. Twelve patients (6.1%) had microscopic cancerous involvement of surgical margin [margin (+) group], and 185 patients had negative surgical resection margins [margin (-) group]. Three patients (25.0%) in the margin (+) group and 11 patients (5.9%) in the margin (-) group had early recurrence. Margin (+) group showed higher incidence of early recurrence and lower incidence of disease free compared to margin (-) group (25.0 vs. 5.9%, p < 0.01; 66.7 vs. 81.1%, p < 0.01, respectively); however, there was no difference in incidence of late recurrence between the two groups (p = 1.00). There were no significant differences in the disease-free survival between the margin (+) and margin (-) groups after exclusion of early recurrence (p = 0.78). CONCLUSIONS: After high-dose radioactive iodine ablation, PTC patients with microscopic cancerous surgical margin involvement had a higher incidence of early recurrence and no different late recurrence rate compared to patients without microscopic cancerous surgical margin involvement. PMID- 22311416 TI - Translationally controlled tumour protein is associated with podocyte hypertrophy in a mouse model of type 1 diabetes. AB - AIMS/HYPOTHESIS: Translationally controlled tumour protein (TCTP) is thought to be involved in cell growth by regulating mTOR complex 1 (mTORC1) signalling. As diabetes characteristically induces podocyte hypertrophy and mTORC1 has been implicated in this process, TCTP may have a role in the pathogenesis of diabetes induced podocyte hypertrophy. METHODS: We investigated the effects and molecular mechanisms of TCTP in diabetic mice and in high glucose-stimulated cultured podocytes. To characterise the role of TCTP, we conducted lentivirus-mediated gene silencing of TCTP both in vivo and in vitro. RESULTS: Glomerular production of TCTP was significantly higher in streptozotocin induced-diabetic DBA/2J mice than in control animals. Double-immunofluorescence staining for TCTP and synaptopodin revealed that podocyte was the principal cell responsible for this increase. TCTP knockdown attenuated the activation of mTORC1 downstream effectors and the overproduction of cyclin-dependent kinase inhibitors (CKIs) in diabetic glomeruli, along with a reduction in proteinuria and a decrease in the sizes of podocytes as well as glomeruli. In addition, knockdown of TCTP in db/db mice prevented the development of diabetic nephropathy, as indicated by the amelioration of proteinuria, mesangial expansion, podocytopenia and glomerulosclerosis. In accordance with the in vivo data, TCTP inhibition abrogated high glucose-induced hypertrophy in cultured podocytes, which was accompanied by the downregulation of mTORC1 effectors and CKIs. CONCLUSIONS/INTERPRETATION: These findings suggest that TCTP might play an important role in the process of podocyte hypertrophy under diabetic conditions via the regulation of mTORC1 activity and the induction of cell-cycle arrest. PMID- 22311417 TI - Coenzyme Q10 prevents GDP-sensitive mitochondrial uncoupling, glomerular hyperfiltration and proteinuria in kidneys from db/db mice as a model of type 2 diabetes. AB - AIMS/HYPOTHESIS: Increased oxygen consumption results in kidney tissue hypoxia, which is proposed to contribute to the development of diabetic nephropathy. Oxidative stress causes increased oxygen consumption in type 1 diabetic kidneys, partly mediated by uncoupling protein-2 (UCP-2)-induced mitochondrial uncoupling. The present study investigates the role of UCP-2 and oxidative stress in mitochondrial oxygen consumption and kidney function in db/db mice as a model of type 2 diabetes. METHODS: Mitochondrial oxygen consumption, glomerular filtration rate and proteinuria were investigated in db/db mice and corresponding controls with and without coenzyme Q10 (CoQ10) treatment. RESULTS: Untreated db/db mice displayed mitochondrial uncoupling, manifested as glutamate-stimulated oxygen consumption (2.7 +/- 0.1 vs 0.2 +/- 0.1 pmol O(2) s(-1) [mg protein](-1)), glomerular hyperfiltration (502 +/- 26 vs 385 +/- 3 MUl/min), increased proteinuria (21 +/- 2 vs 14 +/- 1, MUg/24 h), mitochondrial fragmentation (fragmentation score 2.4 +/- 0.3 vs 0.7 +/- 0.1) and size (1.6 +/- 0.1 vs 1 +/- 0.0 MUm) compared with untreated controls. All alterations were prevented or reduced by CoQ10 treatment. Mitochondrial uncoupling was partly inhibited by the UCP inhibitor GDP (-1.1 +/- 0.1 pmol O(2) s(-1) [mg protein](-1)). UCP-2 protein levels were similar in untreated control and db/db mice (67 +/- 9 vs 67 +/- 4 optical density; OD) but were reduced in CoQ10 treated groups (43 +/- 2 and 38 +/ 7 OD). CONCLUSIONS/INTERPRETATION: db/db mice displayed oxidative stress mediated activation of UCP-2, which resulted in mitochondrial uncoupling and increased oxygen consumption. CoQ10 prevented altered mitochondrial function and morphology, glomerular hyperfiltration and proteinuria in db/db mice, highlighting the role of mitochondria in the pathogenesis of diabetic nephropathy and the benefits of preventing increased oxidative stress. PMID- 22311418 TI - Superior beta cell proliferation, function and gene expression in a subpopulation of rat islets identified by high blood perfusion. AB - AIMS/HYPOTHESIS: The blood perfusion of individual pancreatic islets is highly variable, with a subgroup of islets having high perfusion and blood vessels responsive to further blood flow increase induced by glucose. This study tested the hypothesis that there is heterogeneity between islets with regard to beta cell proliferation, function and gene expression based on differences in their blood perfusion. METHODS: Fluorescent microspheres were injected into the ascending aorta, and then microsphere-containing and non-microsphere-containing pancreatic islets were isolated for investigation. By this procedure, the 5% of islets with the greatest blood perfusion were identified for study. Islet endothelial cells were isolated separately to investigate the role of improved vascular support in the observed differences. RESULTS: The vascular network was found to be more dense and tortuous in microsphere-containing than other islets. The most highly blood-perfused islets also had a higher rate of beta cell proliferation, superior beta cell function and a markedly different gene expression from other islets. Cultured islets exposed to islet endothelial cell products had a similarly increased beta cell proliferation rate, yet significantly fewer changes in gene expression than observed in the most highly blood-perfused islets. CONCLUSIONS/INTERPRETATION: A novel heterogeneity between islets was observed, with superior beta cell proliferation, function and gene expression in a subpopulation of islets identified by high blood perfusion. In contrast with a previously described population of low-oxygenated, sleeping islets, which are recruited into functionality when needed, the presently described heterogeneity is shown to remain in vitro after islet isolation. PMID- 22311419 TI - Oral glucose tolerance test in patients with undiagnosed diabetes and coronary artery disease: when should it be performed? PMID- 22311420 TI - Glycaemic control is improved by 7 days of aerobic exercise training in patients with type 2 diabetes. AB - AIMS/HYPOTHESIS: Cardiovascular events and death are better predicted by postprandial glucose (PPG) than by fasting blood glucose or HbA(1c). While chronic exercise reduces HbA(1c) in patients with type 2 diabetes, short-term exercise improves measures of insulin sensitivity but does not consistently alter responses to the OGTT. The purpose of this study was to determine whether short term exercise training improves PPG and glycaemic control in free-living patients with type 2 diabetes, independently of the changes in fitness, adiposity and energy balance often associated with chronic exercise training. METHODS: Using continuous glucose monitors, PPG was quantified in previously sedentary patients with type 2 diabetes not using exogenous insulin (n = 13, age 53 +/- 2 years, HbA(1c) 6.6 +/- 0.2% (49.1 +/- 1.9 mmol/mol)) during 3 days of habitual activity and during the final 3 days of a 7 day aerobic exercise training programme (7D EX) which does not elicit measurable changes in cardiorespiratory fitness or body composition. Diet was standardised across monitoring periods, with modifications during 7D-EX to offset increases in energy expenditure. OGTTs were performed on the morning following each monitoring period. RESULTS: 7D-EX attenuated PPG (p < 0.05) as well as the frequency, magnitude and duration of glycaemic excursions (p < 0.05). Conversely, average 24 h blood glucose did not change, nor did glucose, insulin or C-peptide responses to the OGTT. CONCLUSIONS/INTERPRETATION: 7D-EX attenuated glycaemic variability and PPG in free-living patients with type 2 diabetes but did not significantly alter responses to the laboratory-based OGTT. These effects appeared to be independent of changes in fitness, body composition or energy balance. ClinicalTrials.gov numbers: NCT00954109 and NCT00972452. FUNDING: This project was funded by the University of Missouri Institute for Clinical and Translational Sciences (CRM), NIH grant T32 AR-048523 (CRM), Diabetes Action Research and Education Foundation (JPT). Medtronic supplied CGMS sensors at a discounted rate. PMID- 22311421 TI - Interspecific competition delays recovery of Daphnia spp. populations from pesticide stress. AB - Xenobiotics alter the balance of competition between species and induce shifts in community composition. However, little is known about how these alterations affect the recovery of sensitive taxa. We exposed zooplankton communities to esfenvalerate (0.03, 0.3, and 3 MUg/L) in outdoor microcosms and investigated the long-term effects on populations of Daphnia spp. To cover a broad and realistic range of environmental conditions, we established 96 microcosms with different treatments of shading and periodic harvesting. Populations of Daphnia spp. decreased in abundance for more than 8 weeks after contamination at 0.3 and 3 MUg/L esfenvalerate. The period required for recovery at 0.3 and 3 MUg/L was more than eight and three times longer, respectively, than the recovery period that was predicted on the basis of the life cycle of Daphnia spp. without considering the environmental context. We found that the recovery of sensitive Daphnia spp. populations depended on the initial pesticide survival and the related increase of less sensitive, competing taxa. We assert that this increase in the abundance of competing species, as well as sub-lethal effects of esfenvalerate, caused the unexpectedly prolonged effects of esfenvalerate on populations of Daphnia spp. We conclude that assessing biotic interactions is essential to understand and hence predict the effects and recovery from toxicant stress in communities. PMID- 22311422 TI - Molecular and life-history effects of a natural toxin on herbivorous and non target soil arthropods. AB - Natural toxins, such as isothiocyanate (ITC), are harmful secondary metabolites produced by plants. Many natural toxins occur in commercial crops, yet their possible negative repercussions on especially non-target soil organisms are largely unknown. This study examined life-history and gene transcriptional responses to 2-phenylethyl ITC on two soil arthropod species: Folsomia candida and Protaphorura fimata. To that end the standardized ISO guideline for ecotoxicological tests and a microarray for F. candida were used. The dissipation of 2-phenylethyl ITC in natural soil was investigated using GC-MS/MS for quantification. Half-lives, tested at four concentration levels in natural soil, were on average 16 h with biodegradation as the plausible main removal process. Regardless, toxic effects on reproduction were shown for F. candida and P. fimata, with EC50 values of around 11.5 nmol/g soil illustrating the toxic character of this compound. Gene expression profiles revealed the importance of fatty acid metabolism at low exposure concentrations (EC10), which is associated with the lipophilic nature of 2-phenylethyl ITC. At higher concentrations (EC50) gene expression became more ubiquitous with over-expression of especially stress related genes and sugar metabolism. The regulation of a gene encoding a precursor of follistatin, furthermore, implied the inhibition of reproduction and may be an important molecular target that can be linked to the observed adverse effect of life-history traits. PMID- 22311423 TI - Characterization the effects of structure and energetics of intermolecular interactions on the oligomerization of peptides in aqueous 2, 2, 2 trifluoroethanol via circular dichroism and nuclear magnetic resonance spectroscopy. AB - Intermolecular interactions are of fundamental importance to fully comprehend a wide range of protein behaviors such as oligomerization, folding and recognition. Two peptides, NPY([18-36]) and NPY([15-29]), segmented from human neuropeptide Y (hNPY), were synthesized in this work to study the interaction between species. Information about intermolecular interactions was extracted from their oligomerizing behaviors. The results from CD and NMR showed that the addition of 2, 2, 2-trifluoroethanol (TFE) induces a stable helix in each peptides and an extended helix in NPY([18-36]), formed between residues 30-36. Pulsed field gradient NMR data revealed that NPY([15-29]) forms a larger oligomer at lower temperatures and continuously dissociates into the monomeric form with increasing temperature. NPY([18-36]) was also found to undergo an enhanced interaction with TFE and a more favorable self-association at higher temperatures. We characterized the changes of oligomerized states with respect to temperature to infer the effects of entropy and interaction energy on the association dissociation equilibrium. As shown by NPY([15-29]), deletion of helical secondary structure or residues from the C-terminal segment may disrupt the solvation by TFE and results in entropy increase as the oligomer dissociates. Unlike that in NPY([15-29]), the extended helix in NPY([18-36]) improves the binding of TFE, and as a result, entropy is gained via the transfer of the TFE cluster from the interface between monomeric peptides into the bulk solvent. This observation suggests that the oligomerized state may be modulated by the entropy and energetics contributed by helical segments in the oligomerization process. PMID- 22311425 TI - Peripheral endocannabinoid microdialysis: in vitro characterization and proof-of concept in human subjects. AB - In vivo endocannabinoid (EC) microdialysis has only seldom been performed, mostly in rodent brain tissue. Low solubility in aqueous media, adsorption to surfaces, and instability with co-present human serum albumin (HSA) are the major obstacles in EC microdialysis. The addition of hydroxypropyl-beta-cyclodextrine (HPCD) to the perfusion fluid has been previously described to facilitate lipid microdialysis, but the general biophysical properties of HPCD, especially with respect to peripheral EC microdialysis, have not been described before. We report on the characterization of EC microdialysis using an in vitro system using Ringer's solution with 10% HPCD as the perfusion fluid and with fatty acid-free HSA as the matrix fluid. The endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2AG) were measured using LC-MS/MS. AEA was stable in the perfusion and matrix fluids, whereas 2AG was only stable in the perfusion fluid. In the matrix fluid, 2AG underwent rapid isomerization to 1-arachidonoyl glycerol. A relative recovery of 3.5% for AEA was found with 10% HPCD in the perfusion fluid and a flow rate of 1 MUL/min. For 2AG, a similar relative recovery of 3.5% was estimated. Since 2AG was found unstable in the matrix fluid, a reliable calculation of the relative recovery rates was not possible. Delivery and recovery experiments revealed unequal inward and outward EC transport across the microdialysis membrane. Contrary to usual microdialysis findings, we observed increasing recovery rates for AEA with increasing flow rates. Long equilibration times of several hours were necessary to obtain constant relative recovery rates. In a proof-of-concept study in humans, we collected AEA from subcutaneous abdominal adipose tissue employing the described methodology. Our study suggests that the microdialysis technique is not suitable for the exact quantification of tissue EC concentrations, but it allows for their rough estimation. PMID- 22311424 TI - Exploring the feasibility of bioaerosol analysis as a novel fingerprinting technique. AB - The purpose of this review is to investigate the feasibility of bioaerosol fingerprinting based on current understanding of cellular debris (with emphasis on human-emitted particulates) in aerosols and arguments regarding sampling, sensitivity, separations, and detection schemes. Target aerosol particles include cellular material and proteins emitted by humans, animals, and plants and can be regarded as information-rich packets that carry biochemical information specific to the living organisms present where the sample is collected. In this work we discuss sampling and analysis techniques that can be integrated with molecular (e.g. protein)-detection procedures to properly assess the aerosolized cellular material of interest. Developing a detailed understanding of bioaerosol molecular profiles in different environments suggests exciting possibilities of bioaerosol analysis with applications ranging from military defense to medical diagnosis and wildlife identification. PMID- 22311426 TI - Common wheat determination in durum wheat samples through LC/MS analysis of gluten peptides. AB - A method to detect the presence of common wheat in durum wheat flour samples was developed and tested. Flour samples, or ground wheat samples, were digested by pepsin and chymotrypsin, and the peptide mixture obtained was analyzed by LC/ESI MS and LC/ESI-MS/MS, which led to the identification of two marker peptides. One peptide was coded only in the DD genome, and thus present only in common wheat; the second was present in all wheat samples (both common and durum), so it was used as marker of the total wheat content. The ratio of the chromatographic areas of these two peptides, as determined by LC/ESI-MS, was related to the proportion of common wheat in the sample using a calibration curve that was constructed with standards of known composition. The proportions of common wheat in samples obtained by mixing different common and durum wheat varieties were accurately determined by this method. Finally, the method was applied in a survey of several durum wheat flour brands present on the Italian market. The results of the survey revealed that contamination of durum wheat flour with common wheat is commonplace. PMID- 22311427 TI - Engineered cells as biosensing systems in biomedical analysis. AB - Over the past two decades there have been great advances in biotechnology, including use of nucleic acids, proteins, and whole cells to develop a variety of molecular analytical tools for diagnostic, screening, and pharmaceutical applications. Through manipulation of bacterial plasmids and genomes, bacterial whole-cell sensing systems have been engineered that can serve as novel methods for analyte detection and characterization, and as more efficient and cost effective alternatives to traditional analytical techniques. Bacterial cell-based sensing systems are typically sensitive, specific and selective, rapid, easy to use, low-cost, and amenable to multiplexing, high-throughput, and miniaturization for incorporation into portable devices. This critical review is intended to provide an overview of available bacterial whole-cell sensing systems for assessment of a variety of clinically relevant analytes. Specifically, we examine whole-cell sensing systems for detection of bacterial quorum sensing molecules, organic and inorganic toxic compounds, and drugs, and for screening of antibacterial compounds for identification of their mechanisms of action. Methods used in the design and development of whole-cell sensing systems are also reviewed. PMID- 22311428 TI - Sr isotope measurements in beef-analytical challenge and first results. AB - The strontium isotope ratio ((87)Sr/(86)Sr) in beef, derived from 206 European cattle, has been measured. These cattle were located in 12 different European regions within France, Germany, Greece, Ireland, Italy, Spain and the UK. As animal protein is known to be a difficult material on which to conduct Sr isotope analysis, several investigations were undertaken to develop and improve the sample preparation procedure. For example, Sr isotope analysis was performed directly on freeze-dried meat and defatted dry mass from the same samples. It was found that enormous differences-sometimes exceeding the measurement uncertainty could occur between the fractions and also within one sample even if treated in the same manner. These variations cannot be definitely allocated to one cause but are most likely due to inhomogeneities caused by physiological and biochemical processes in the animals as post mortem contamination during analytical processing could be excluded. For further Sr isotope measurements in meat, careful data handling is recommended, and for the authentic beef samples within this project, it was decided to use only freeze-dried material. It can be demonstrated, however, that Sr isotope measurements in beef proteins are a valuable tool for authentication of geographic origin. Although partly overlapping, some of the European sampling sites could be discriminated even by only using (87)Sr/(86)Sr. PMID- 22311429 TI - Evaluating the prevalence and molecular epidemiology of echovirus 11 isolated from sewage in Shandong Province, China in 2010. AB - Echovirus 11 (E11) is an important human pathogen, but its genetic information in China is in scarce. In this study, 12 sewage samples from Jinan city and 18 from Linyi city were collected in Shandong Province, China in 2010, and E11 was the predominant serotype with 54 isolates from 16 samples. Numbers of E11 isolates reached peaks in August in both Jinan and Linyi city, while another peak occurred in December in Linyi. The complete VP1 genes of all these isolates were sequenced and phylogenetically compared with clinical isolates from Shandong in 1994-2010 (n = 29) and global E11. Shandong isolates segregated into five clusters, four in genogroup A and one in genogroup C. Environmental isolates belonged to two clusters of genogroup A, with high inter-cluster genetic divergence (18.5-20.9%). No local clinical E11 was isolated in the two cities in 2010, revealing the value of environmental surveillance in investigating circulating viruses. These findings underscored the significance of environmental VP1 sequence divergences in comprehending the local enterovirus circulation, and updated the global molecular epidemiology of E11. PMID- 22311430 TI - Identification of a new Bombyx mori nucleopolyhedrovirus and analysis of its bro gene family. AB - The highly pathogenic Bombyx mori nucleopolyhedrovirus (BmNPV) has caused severe damages to sericulture in many countries, and the relationship between the pathogenicity of various BmNPV strains and their geographical evolution has been the topic of our interest. In this study, we isolated a new BmNPV strain from Thailand (BmNPV-Thai), based on the sequences of its conservative genes p10, p35, polh, egt and vp39. The BmNPV-Thai appears to have baculovirus repeated ORF (bro) genes different from four other well-known BmNPV strains of China (GD, CQ1), Japan (T3), and France (SC7); It only has bro-a, bro-c, and bro-d, but not bro-b and bro-e genes. These bro genes are localized only in the two subgroups highly homologous to their counterparts and their encoded BRO proteins differ mainly at their N-terminal amino acid residues. Phylogenetic analysis indicates that the evolution of the bro genes of the five BmNPV strains is not obviously associated with their geographic locations. PMID- 22311431 TI - WHO grade III anaplastic meningioma metastasizing to the parotid gland and the lungs: case report and review of the literature. PMID- 22311432 TI - Serum vitamin D level and bone mineral density in premenopausal Egyptian women with fibromyalgia. AB - Patients with fibromyalgia syndrome (FMS) have impaired mobility and therefore get less sunlight exposure, we postulated that they may be at increased risk of developing osteoporosis (OP). The aim of this study was to assess and compare serum vitamin D level and bone mineral density (BMD) value in patients with primary FMS (PFMS) and healthy controls. A total of 50 patients with PFMS participated in this case-control study, and 50 healthy females who were age matched to the patients were used as the control group. Venous blood samples collected from all subjects were used to evaluate serum 25-hydroxyvitamin D3 (25 OHD). BMD was measured at the lumbar spine (L2-L4) anteroposterior, femoral neck and forearm by dual-energy X-ray absorptiometry. Patients with PFMS had significantly lower serum 25-OHD than controls (15.1 +/- 6.1 and 18.8 +/- 5.4 ng/ml, respectively, p = 0.0018). Apart from the BMD in the lumbar spine, which was significantly lower in the PFMS patients compared with controls (p = 0.0012), no significant difference was found in other measures of BMD. Compared to PFMS patients who had serum level of the 25-OHD >20 ng/ml, the patients with 25-OHD <=20 ng/ml are more likely to have impaired short memory (46.4 vs. 13.6%, respectively, p = 0.0136), confusion (50 vs. 18.2%, respectively, p = 0.0199), mood disturbance (60.7 vs. 27.3%, respectively, p = 0.0185), sleep disturbance (53.6 vs. 22.7%, respectively, p = 0.0271), restless leg syndrome (57.1 vs. 27.3%, respectively, p = 0.0346) and palpitation (67.9 vs. 36.4%, respectively, p = 0.0265). Serum level of the 25-OHD is inversely correlated with visual analogue scale (VAS) of pain (p = 0.016), Beck score for depression (p = 0.020) and BMD at lumbar spine (p = 0.012). The lumbar BMD inversely correlated with VAS of pain (p = 0.013) and Beck score for depression (p = 0.016). This study confirmed high prevalence of hypovitaminosis D among in patients with PFMS. This study confirmed the concept that FMS is a risk factor for OP. Based on this, an early nutrition program rich in calcium and vitamin D, appropriate exercise protocols, and medical treatment should be considered in these patients in terms of preventing OP development. PMID- 22311433 TI - Proprotein convertase subtilisin/kexin type 9: a new target molecule for gene therapy. AB - Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a novel target for controlling plasma levels of low-density lipoprotein cholesterol (LDL C) and decreasing the risk of cardiovascular diseases. At present it is clear that the major classes of commonly prescribed lipid-lowering medications increase serum PCSK9 levels and fail to protect a significant percentage of patients from cardiovascular events. Therefore development of new LDL-C lowering medications that either do not increase circulating PCSK9 levels or work through inhibition of PCSK9 expression and protease activity is a highly desirable approach to overcome hypercholesterolemia. Since there are several agents which are being evaluated in human preclinical and clinical trials, this review summarizes current therapeutic strategies targeting PCSK9, including specific antibodies, antisense oligonucleotides, small interfering RNAs (siRNAs) and other small molecule inhibitors. PMID- 22311436 TI - Cavitation engineered 3D sponge networks and their application in active surface construction. AB - The design of the 3D architecture surfaces with both space- and time-dependent functionality (cell attraction, pH-trigged self-cleaning, antiseptic/disinfection) is in the focus. The innovative story includes: sonochemical surface activation, formation of feedback surface component (pH responsible micelles), proof of responsive activity (time resolved cell adhesion and bacteria deactivation) and space adhesion selectivity (surface patterning). PMID- 22311437 TI - Alcohol septal ablation after transaortic valve implantation: the dynamic nature of left outflow tract obstruction. AB - Transcatheter aortic valve implantation (TAVI) has emerged as a less invasive and potentially high efficacious procedure for the treatment of high-risk patients with symptomatic aortic stenosis. Appropriate patient selection for TAVI is a key component to ultimate clinical success. Herein, we describe a patient with left ventricular outflow tract (LVOT) obstruction that became apparent only following relief of aortic stenosis with TAVI. This report highlights the dynamic nature of LVOT obstruction, which was successfully treated in our patient with catheter based alcohol septal ablation. The potential to unmask dynamic LVOT obstruction with TAVI should be an important consideration in patient selection for the procedure, and the postoperative assessment of these patients. PMID- 22311438 TI - [Management of venous thromboembolism in psychiatric patients]. AB - BACKGROUND: Several studies conducted in psychiatric populations, have reported the promoting and pejorative role of psychiatric community in thrombogenesis. AIMS: To clarify the specificity of psychiatric community in deep vein thrombosis (DVT) and to propose a set of general recommendations for appropriate care. METHODS: We searched MEDLINE (PubMed) between 1956 and 2010. We reviewed article titles and abstracts and full text of selected studies of psychiatric patients with venous thromboembolism disease. We identified 50 studies that investigated the association between psychiatric disease and venous thromboembolism events. RESULTS: In psychiatric community venous thromboembolism disease has several characteristics: epidemiological, clinical and evolutionary and is conditioned by a combination of several thromboembolism risk factors: - Linked in part to the psychiatric illness itself, - But above all specific therapeutic methods in psychiatric community (anti-psychotic, restraint...) which are easily preventable. CONCLUSION: Besides the medical side, the psychiatric community itself is characterized by a large number of variables, giving a particularly encouraging and derogatory about the advent and development of VTE. PMID- 22311439 TI - [The barotraumatic ENT pain in military personnel]. PMID- 22311440 TI - [NK/T lymphoma]. PMID- 22311441 TI - [Malignant tumours of parotid]. PMID- 22311442 TI - [Etiologic profile of amyloidosis of the elderly in Tunisia]. AB - BACKGROUND: The amyloidosis is one of the histologic lesions the most frequently associated to the aging. AIM: To identify the several etiologies of amyloidosis in elderly patients according to immunohistochemical type. METHODS: Retrospective study on 10 years, in Internal medicine and Nephrology department in Charles Nicolle Hospital. Tunis. Tunisia. Diagnosis of amyloidosis was retained after histological confirmation with specific colorations, in patients aged 65 years or more at the diagnose of amyloidosis. RESULTS: The study enrolled 51 patients with amyloidosis. In 67% of cases it was AA amyloidosis. The etiology the most frequently observed with this type was the tuberculosis, followed by chronic pulmonary infections. We retained diagnose of non AA amyloidosis in 21% of patients. The multiple myeloma has been the most frequent etiology observed, but no cause was identified at about half of patients. Twelve per cent of amyloidosis were not typed. CONCLUSION: From our study, we can remark the high predominance of AA amyloidosis, probably because of frequency of tuberculosis which is still high in our country, this is not in accordance with occidental data, were AL amyloidosis and senile amyloidosis predominate in elderly. PMID- 22311443 TI - [Cystic hygroma : report of 25 cases]. AB - BACKGROUND: The cystic hygroma is a benign lymphatic malformation, a rare but potentially serious in its character and its evolutionary trend dissecans. The head and neck region constitutes the favorite seat (75%). If the diagnosis is usually easy, the therapeutic management remains controversial. AIM: To analyze clinical and paraclinical characteristics of cystic hygroma and to discuss the various therapeutic methods. METHODS: We report a retrospective study about 25 cases of head and neck cystic hygroma collected during a period of 11 years (1998 2008) in the ENT department of the hospital The Rabta Tunis. RESULTS: The average age of our patients was 18 years and 5 months. All patients consulted for a neck mass. It was localized in the submandibular region in 7 cases, 3 cases in parotid region, jugulocarotid artery in 3 cases and affecting the posterior triangle in 12 cases. Cervical ultrasound was performed in 22 cases (88%) evoking the diagnosis of cystic hygroma in 16 cases (72%). CT was performed in 10 cases finding hypodense aspect in 8 cases. MRI was carried out in 9 cases. It showed the aspect hyperintense T2, hypointense T1 in 7 cases. Surgical excision was performed in 22 cases and sclerotherapy in 3 patients. During the evolution, a recurrence was observed for each treatment modality. CONCLUSION: Surgery is treatment of choice of cystic hygroma. Sclerotherapy may be indicated as an alternative to surgery in localized and diffuse macrocystic forms. PMID- 22311444 TI - [Epidemiology of pediatric traumatic brain injury at the Children's Hospital of Tunisia, 2007]. AB - BACKGROUND: The traumatic brain injury is a major cause of morbidity and mortality in the paediatric population. Adequate knowledge of their epidemiology is necessary to develop targeted preventive campaigns, and to estimate the needs for care facilities. AIM: To specify the demographic and epidemiologic characteristics of paediatric traumatic brain injury. METHODS: Longitudinal retrospective study including children hospitalized for traumatic brain injury in the Hospital of Child of Tunis during the 1-year period (2007). RESULTS: Our study comprised 298 children with an average age of 5.9 +/- 3.9 years and a sex ratio with 2. Minor traumatic brain injury represented 92.6 % of the cases and severe traumatic brain injury represented 5.4 %. One child of 6 had another traumatism. Accidents at home were the most frequent causes (64.1 %). Traffic accidents represented 27.9 % of the mechanisms. In 90.6 % of the cases the transport was assured by clean means. The cerebral scanner, produced at 89.9 % of the patients, revealed cerebral lesions in 49.7% of the cases. Neurosurgical indications were carried in 5 children. The death rate was 2.1 %. At three months of the exit of the hospital, 97.2 % of the children had a good recovery. CONCLUSION: The paediatric traumatic brain injury is a frequent and serious pathology. The epidemiologic studies can contribute to the development of prevention program in order to decrease its incidence in the target population. PMID- 22311445 TI - Clarithromycin versus metronidazole in first-line Helicobacter pylori eradication. Prospective randomized study of 85 Tunisian adults. AB - BACKGROUND: Although primary resistance to metronidazole remains high (56,8%), it is more widely used than clarithromycin as a firstline Helicobacter pylori (H. pylori) treatment in the common Tunisian practice. AIM: To compare the eradication rate in two protocols including clarithromycin versus metronidazole in Tunisian adults. METHODS: From July 2005 to December 2007, 85 patients aged 18 to 75 years presenting with gastro-duodenal lesions with H. pylori infection and requiring its eradication were included in the study. They were randomized to receive alternatively a seven-day triple therapy including: Omeprazole + Amoxicillin + Clarithromycin (OAC group) or Metronidazole (OAM group) twice a day. A second endoscopy with new biopsies was carried out 6 weeks after treatment to control eradication. RESULTS: Eighty five patients finished the protocol. The OAC and OAM groups included 46 and 39 patients respectively. They were comparable with respect to age, gender, clinical presentation and initial lesions. The total eradication rate was 60%. It was significantly higher in the clarithromycin group (69.6%) than in the metronidazole group (48.7%): p < 0.05. CONCLUSION: Clarithromycin is more effective than metronidazole in H. pylori eradication. It should be made available in our hospital's nomenclature. This would prevent iterative eradication courses and probably reduce treatment cost. PMID- 22311446 TI - Metabolic syndrome in Tunisian obese children and adolescents. AB - AIM: To determine the frequency of cardiovascular risk factors and the prevalence of metabolic syndrome (MS) in obese children and adolescents. METHODS: This cross sectional study concerned 186 obese children and adolescents (137 girls and 49 boys), between the ages of 6 and 18 years, recruited in the research unit on human obesity of the National Institute of Nutrition between December 2007 and October 2008. Metabolic syndrome was defined with the International Diabetes Federation (IDF) criteria. RESULTS: The frequency of MS was 34.4%. It was higher in males (40.8%) than in females (32.1%) but without statistical significance (p=0.27). Body mass index and waist circumference were significantly higher in subjects with metabolic syndrome than that of subjects without metabolic syndrome. The frequency of MS increases with age. Family history of obesity, birth weight and breastfeeding did not influence the prevalence of MS. The most common component, associated with abdominal obesity, was Glucose tolerance abnormalities observed in 51 % of the sample. 65.6% of subjects with MS had 3 criteria of the five proposed by the IDF. CONCLUSION: Metabolic syndrome is prevalent in our young obese population. Early identification of young at risk is crucial to the prevention of early cardiovascular diseases. PMID- 22311447 TI - Prognostic value of preoperative carcinoembryonic antigen level in colorectal cancer in Tunisia. AB - AIM: To evaluate the prognostic value of preoperative serum carcino-embryonic antigen (CEA) level in patients with colorectal cancer. METHODS: This retrospective study included 125 colorectal cancer patients aged from 14 to 87 years, surgically treated between January 2001 and December 2006. Preoperative serum CEA was measured by chemiluminescence assay. RESULTS: within the patients, 57 were males and 68 females. They have tumours classified Dukes A in 2 patients, B in 24 patients, C in 53 patients and Dukes D in 46 patients. Median follow-up period was 24 months (range, 4 - 72 months). The relapse-free survival was significantly higher in patients with CEA < 5 ng/ml compared to CEA 3 5 ng/ml, (p < 0.0001). We observed significant differences in relapse-free survival between patients with CEA < 5 ng/ml and those with CEA 3 5 ng/ml among patients classified as Dukes stage B (p=0.007) and C (p < 0.0001). However, there was no significant difference in relapse-free survival among those classified as Dukes stage D. Cox multivariate analysis demonstrated that preoperative serum CEA level was a significant independent prognostic factor for relapse-free survival (hazard ratio: 6.49, 95% CI, 3.09 to 13.62, p < 0.0001). CONCLUSION: Preoperative serum CEA is a reliable predictor factor for recurrence in patients with CRC. CEA might be used in staging system and will be useful for therapeutic orientation in patients undergoing curative resection of CRC. PMID- 22311448 TI - Cutaneous adverse drug reactions in children. A series of 90 cases. AB - BACKGROUND: Cutaneous adverse drug reactions (CADR) are frequent in children. They have different clinical presentations and may be caused by several drugs. AIM: To evaluate the epidemioclinical features of cutaneous adverse drug reactions (CADR) and the different causative drugs in a Tunisian paediatric series. METHODS: We have retrospectively included 90 children (under 16 years old) with a well documented cutaneous drug reaction, seen in the Department of Dermatology of Charles Nicolle hospital of Tunis over 18 years (1991-2008). Age, gender, duration of skin disorders, type of cutaneous lesions, incriminated drugs, delay between drug consumption and eruption, validation by the national pharmacovigilance centre, treatment and outcome were recorded. RESULTS: Our patients were 6.9 year-aged (sex-ratio M/F 1.19). They had maculopapular eruption (MPE) (57.7%), acute urticaria (16.6%), fixed drug eruption (14.4%), erythema multiform (2.2%), photosensitization (1.1%) or severe cutaneous drug reactions (10%).Incriminated drugs were: Antibiotics (55.5%), non-steroidal antiinflammatory drugs (18.8%), antiepileptics (11.1%), and analgesics (5.5%). Betalactamins were the most commonly incriminated antibiotics (32 out of 50 patients; 64%). Barbiturates were the most commonly incriminated anti-epileptics (7/90 cases, 7.7%). Favourable outcome was noted in all patients, even those with severe drug reactions. CONCLUSION: MPE to antibiotics were the most common kinds of CADR in children. Drug responsibility should be based on solid criteria given the frequency of MPE of infectious origin and the frequent prescription of antibiotics in paediatric population. PMID- 22311449 TI - Spirometric reference values for children living in Constantine (Eastern region of Algeria). AB - BACKGROUND: Spirometry play an important role in diagnosing obstructive lung disease, assessing the severity of lung disease, monitoring treatment of patients with respiratory disorders, and allocating patients to treatment groups in drug intervention studies. Since spirometric lung function depends on body size, age, gender and ethnic group, reference equations derived from healthy individuals are imperative for interpreting results. AIM: To assess the need for spirometric norms for children 5 to 16 years old and living in Constantine (Eastern region of Algeria). METHODS: Anthropometric and spirometric data were measured in 208 healthy children (101 girls) living in Constantine (649 m above sea level). RESULTS: Published reference equations did not reliably predict measured spirometric data in Constantinian children. Combination of gender, age, height, weight, body mass index and body surface area explained between 69% and 94% of the spirometric data variability's. FEV1/FVC ratio [means+/-SD (5th percentiles) were0.91+/-0.06 (0.80) for boys and 0.90+/-0.06 (0.81) for girls] was not included in the regression because of its relative independence of anthropometric data. The mean+/-SD of the forced expiratory time was 2.44+/-0.74 s and only 27% of children reached the threshold of 3 3 s. In an additional group of 24 children prospectively studied, the agreement between measured and predicted FEV1 was satisfactory. CONCLUSION: Our reliable spirometric reference equations provide a useful norm for the care of paediatric patients living in the Eastern region of Algeria. The present study enriches the World Bank of reference equations, from which physicians should choose according to where patients live and their ethnic background. PMID- 22311450 TI - [Trastuzumab (herceptin) for the medical treatment of breast cancer]. AB - BACKGROUND: Trastuzumab is humanized monoclonal antibody targeting her 2 neu receptor, overexpressed in 20% of breast cancers and part of the complex of Epidermal Growth Factor Receptor. AIM: To review new advances in the knowledge of the practical use of "trastuzumab (Herceptin (r))" in breast cancer. METHODS: Review of literature using medical data bases (Medline, Science direct) with the following key words: breast cancer, targeted therapy, HER2 neu, transtuzumab/herceptine RESULTS: Trastuzumab represent an important advance in breast cancer treatment with an improvement of median survival in metastatic setting and overall and disease-free survival in adjuvant setting in association with chemotherapy. Herceptin remain well tolerated with a low and rare risk of cardiac failure. CONCLUSION: Trastuzumab is a new therapeutic tool very interesting to ameliorate prognosis of breast cancer. PMID- 22311451 TI - [Carpal tunnel syndrome. A Tunisian series]. AB - BACKGROUND: Carpal tunnel syndrome (CTS) is the most frequent ductal syndrome. Few epidemiological studies in Tunisia exist. AIM: To describe clinical, biological and electromyographic data of Tunisian patients with CTS METHODS: A retrospective study including 80 patients with CTS, during the period going from 2009 to 2010. RESULTS: A female predominance was observed with an average age of 52 years. Acroparesthesia was the main complaint, followed by night awakenings and muscular weakness. Physical examination showed a positive Tinel (91.2%) and Phalen (82.5%) tests, a decrease of tactile sensitivity (26.2%) and a thenar amyotrophy (10%). The Electromyography was abnormal in 85% cases. The most revealing lesions were demyelinating, sensitivo-motor predominance (66%) abnormalities. on Biology, hyperglycemia (12.5%), hyperuricemia (8.7%) and renal failure (7.5%) were the most observed. Medical treatment was drawn on analgesics and anti-inflammatory for 90% of our patients. Local steroid injections were indicated for 35% of patients, leading to a clinical improvement in 90% of cases. Surgery was made in only 13.8% patients. CONCLUSION: Tunisian patients with CTS were female patients, housewifes with obesity or overweight. No other differences were observed in comparison with the literature. PMID- 22311452 TI - Iatrogenic esophageal perforation in the neonate. AB - BACKGROUND: Esophageal perforation is uncommon and often iatrogenic. AIM: To report a neonatal case of esophageal perforation. CASE: A premature newborn boy was admitted with a diagnosis of oesophageal atresia after several unsuccessful attempts to insert an orogastric tube. A chest x-ray showed a "high pouch" with a gasless intestine. At operation, no atresia was found and a large traumatic perforation of the lower cervical segment was identified, requiring cervicotomy and primary closure. Oral feeding was started after 3 weeks. As a result, nosocomial sepsis occurred, causing death in the third month after surgical treatment. CONCLUSION: Oesophageal perforation in the neonate is often iatrogenic and may mimic oesophageal atresia. The authors highlight the importance of early diagnosis and management. PMID- 22311453 TI - Adenocarcinoma arising in the 'J' pouch after total proctocolectomy for familial polyposis coli. PMID- 22311454 TI - [Intrapancreatic gastric duplication cyst]. PMID- 22311455 TI - [Squamous endobronchial papillomatosis]. PMID- 22311456 TI - [Fibrous dysplasia of bone associated with and without McCune Albright syndrome]. PMID- 22311457 TI - [Uveitis, interstitial nephritis and hepatitis with cytomegalovirus in an immunocompetent adult]. PMID- 22311458 TI - [A rare uterine tumor in a 17 year-old girl]. PMID- 22311459 TI - The dose-dependent effects of endotoxin on protein metabolism in two types of rat skeletal muscle. AB - Endotoxin administration is frequently used as a model of systemic inflammatory response which is considered the important pathogenetic factor in muscle wasting development in severe illness, such as sepsis, cancer, injury, AIDS and others. The main purpose of this study was determining the effect of various doses of endotoxin on protein and amino acid metabolism in two types of rat skeletal muscle. Sepsis was induced by intraperitoneal administration of endotoxin in a dose of 1, 3 and 5 mg/kg body weight (bw); control animals received a corresponding volume of the saline solution. After 24 h, extensor digitorum longus (EDL) and soleus (SOL) muscles were isolated and used for determination of total and myofibrillar proteolysis, protein synthesis, activity of cathepsins B and L, chymotrypsin-like activity of proteasome and amino acid release. The endotoxemia induced the body weight loss, the rise of total cholesterol and triglyceride plasma concentration and the protein catabolic state in skeletal muscle, which was caused by a higher increase in protein breakdown (due to activation of the proteasome system) than protein synthesis. The more significant effect of endotoxin was seen in EDL than SOL. The dose of 5 mg of endotoxin/kg bw induced the most significant changes in parameters of the protein and amino acid metabolism measured and could be therefore considered appropriate for studies of protein catabolism in young rat skeletal muscle at 24 h after endotoxin treatment. PMID- 22311460 TI - A microfluidic approach to encapsulate living cells in uniform alginate hydrogel microparticles. AB - A microfluidic technique is described to encapsulate living cells in alginate hydrogel microparticles generated from monodisperse double-emulsion templates. A microcapillary device is used to fabricate double emulsion templates composed of an alginate drop surrounded by a mineral oil shell. Hydrogel formation begins when the alginate drop separates from the mineral oil shell and comes into contact with Ca(2+) ions in the continuous phase. Alginate hydrogel microparticles with diameters ranging from 60 to 230 um are obtained. 65% of the cells encapsulated in the alginate microparticles were viable after one week. The technique provides a useful means to encapsulate the living cells in monodisperse hydrogel microparticles. PMID- 22311461 TI - Impaired cell adhesion, apoptosis, and signaling in WASP gene-disrupted Nalm-6 pre-B cells and recovery of cell adhesion using a transducible form of WASp. AB - Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency disease affecting cell morphology and signal transduction in hematopoietic cells. The function of Wiskott-Aldrich syndrome protein (WASp) and its partners in protein interaction have been studied intensively in mice; however, detailed biochemical characterization of its signal transduction and assessment of its functional consequence in human WASp-deficient lymphocytes remain difficult. In this study, we generated Nalm-6 cells in which the WAS protein gene (WASP) was disrupted by homologous recombination-based gene targeting and a cell-permeable form of recombinant WASp for functional study. The WASP-/- cells showed impaired adhesive capacity and polarization to plate-bound anti-CD47 mAb, anti-CD9 mAb, or to fibronectin. The defective morphological changes were accompanied by impaired intracellular signaling. In addition, the WASp-deficient cells displayed augmented apoptosis induced by CD24 cross-linking. A recombinant fusion protein composed of Hph-1 cell-permeable peptide and WASp prepared in Escherichia coli. Hph-1-WASp was efficiently transduced and expressed in WASP-/- Nalm-6 cells in a dose-dependent manner. The wild-type WASp, but not the mutant restored adhesion capacity, spreading morphology, and cytoskeletal reorganization. Additionally, the recombinant protein was successfully transduced into normal lymphocytes. These findings suggest that gene-disrupted model cell lines and cell-permeable recombinant proteins may serve as important tools for the detailed analysis of intracellular molecules involved in PID. PMID- 22311462 TI - Guest editorial: mutual relationship between vascular biology and hematology. PMID- 22311463 TI - New functions of the fibrinolytic system in bone marrow cell-derived angiogenesis. AB - Angiogenesis is a process by which new blood vessels form from preexisting vasculature. This process includes differentiation of angioblasts into endothelial cells with the help of secreted angiogenic factors released from cells such as bone marrow (BM)-derived cells. The fibrinolytic factor plasmin, which is a serine protease, has been shown to promote endothelial cell migration either directly, by degrading matrix proteins such as fibrin, or indirectly, by converting matrix-bound angiogenic growth factors into a soluble form. Plasmin can also activate other pericellular proteases such as matrix metalloproteinases (MMPs). Recent studies indicate that plasmin can additionally alter cellular adhesion and migration. We showed that factors of the fibrinolytic pathway can recruit BM-derived hematopoietic cells into ischemic/hypoxic tissues by altering the activation status of MMPs. These BM-derived cells can function as accessory cells that promote angiogenesis by releasing angiogenic signals. This review will discuss recent data regarding the role of the fibrinolytic system in controlling myeloid cell-driven angiogenesis. We propose that plasmin/plasminogen may be a potential target not only for development of effective angiogenic therapeutic strategies for the treatment of cancer, but also for development of strategies to promote ischemic tissue regeneration. PMID- 22311464 TI - Abnormal tumor vasculatures and bone marrow-derived pro-angiogenic cells in cancer. AB - Tumor-derived factors affect the stroma of cancer tissue by activating pro angiogenic signals. One of the key components of this response is the mobilization of the pro-angiogenic cells from bone marrow (BM), which contribute to the development of abnormal tumor vasculature. Evidence is accumulating that the pro-angiogenic cells derived from BM are involved in the physiological processes of tissue repair and wound healing. However, vascular structure in cancer tissue is impaired, resulting in the formation of chaotic neo-vessels and hypoxic microenvironments. Ultimately, these structural and functional abnormalities result in the limited delivery of chemotherapeutic agents and create regions of metabolic derangement, both of which enhance resistance to chemotherapy. In spite of recent advances in targeted therapy using anti-vascular agents, clinical results from studies using individual agents have unsatisfactory, necessitating the combinatorial use of anti-cancer drugs and a targeting agent. We suggest the possibility of a new therapeutic approach in which aberrant tumor vessels are normalized by BM-derived pro-angiogenic cells, and the delivery of anti-cancer drugs is maximized. In this review, we focus on the current understanding of the structure and function of tumor vessels, and an alternative approach to the repair of abnormal tumor vasculature by the use of BM derived pro-angiogenic cells. This approach may improve both the delivery and the efficacy of anti-cancer drugs by restoring aberrant tumor vascularization and hypoxia. PMID- 22311465 TI - Near-infrared fluorescence imaging of lymphatics in head and neck lymphedema. AB - BACKGROUND: Lymphedema is a complication that may occur after surgical resection and radiation treatment in a number of cancer types and is especially debilitating in regions where treatment options are limited. Although upper and lower extremity lymphedema may be effectively treated with manual lymphatic drainage (MLD) therapies and devices that use compression to direct proximal flow of lymph fluids, head and neck lymphedema is more challenging. METHODS AND RESULTS: Herein, we describe the compassionate use of an investigatory technique of near-infrared (NIR) fluorescence imaging to understand the lymphatic anatomy and function, help direct MLD, and use 3-dimensional (3D) surface profilometry to monitor response to therapy in a patient with head and neck lymphedema after surgery and radiation treatment. CONCLUSION: NIR fluorescence imaging provides a mapping of functional lymph vessels for direction of efficient MLD therapy in the head and neck. Additional studies are needed to assess the efficacy of MLD therapy when directed by NIR fluorescence imaging. PMID- 22311466 TI - Oncogenic osteomalacia from nasal cavity giant cell tumor. AB - BACKGROUND: Oncogenic osteomalacia is a rare paraneoplastic syndrome characterized by osteomalacia, which occurs as a result of excess renal phosphate excretion caused by fibroblast growth factor-23 secreted by mesenchymal tumors. This entity is rare in head and neck cancers. We report a rare case of oncogenic osteomalacia in a patient with an anterior skull base giant cell tumor. METHODS AND RESULTS: A 34-year-old woman presented with a 5-year history of progressive weakness in both lower limbs and the trunk. Hypophosphatemia and hypocalcemia had been noted by a local physician, but her symptoms persisted despite receiving calcium and vitamin D supplements. A recent onset of epistaxis and nasal blockage led to referral to the head and neck services. Nasal endoscopy revealed a left nasal cavity mass. Further evaluation with imaging studies revealed a mass in the nasal cavity with intracranial extension. Biopsy of the lesion suggested a neurogenic tumor. A putative diagnosis of anterior skull base neurogenic tumor with paraneoplastic hypophosphatemia was made. After the biochemical parameters were corrected, the patient underwent craniofacial resection. The final histopathologic study suggested the lesion as a "giant cell tumor." During the postoperative period the patient's biochemical and clinical symptoms improved dramatically, allowing her to regain normal mobility. CONCLUSIONS: Clinicians and pathologists must be aware of the clinical symptoms, laboratory abnormalities, and pathologic features of oncogenic osteomalacia, which may be caused by tumors in the head and neck and thus make an exhaustive effort to diagnose the same. PMID- 22311467 TI - Corticomotor control of deep abdominal muscles in chronic low back pain and anticipatory postural adjustments. AB - Contralateral transversus abdominis muscle (cTrA) is known to be anticipatory to rapid focal movement. The activation of ipsilateral TrA (iTrA) follows cTrA, but their anticipatory interaction in healthy subjects seems to be delayed in low back pain (LBP) patients. TrA delay in LBP is linked with reorganization of the primary motor cortex (M1), thus supporting that cortical changes underlie the altered postural control. Our study tested whether differences in postural adjustments were present in LBP for TrA onsets and co-activation, and whether these differences were paralleled by cortical motor changes. Thirteen chronic LBP patients and 9 healthy Controls were enrolled. Surface recordings of cTrA/internal oblique (IO) and iTrA/IO were collected during a rapid shoulder flexion task while standing. Transcranial magnetic stimulation of M1 tested TrA/IO corticospinal excitability, active motor threshold and short-interval intracortical inhibition (SICI). In LBP compared to Controls, iTrA/IO activation was delayed, co-activation was absent, timing between TrA/IO onsets was impaired, and SICI was missing. Between-outcomes correlations observed in one group were not significant in the other. Delay of iTrA/IO and the lacking co-activation were not explained by between-group differences of transcranial magnetic stimulation outcomes. TrA/IO co-activation is present during rapid focal movement in healthy subjects only. LBP patients displayed an important alteration of the control of spine stability that can be explained by altered mechanisms of M1 motor programming. PMID- 22311468 TI - Reaction times and perceptual adjustments are sensitive to the illusory distortion of space. AB - The Oppel-Kundt illusion (OKI) consists of the perception of a filled space as larger than an empty space of the same size. Here, we used a modified version of that illusion composed of a gradient of vertical lines whose spacing decreased progressively from one side to the other: space is expected to be perceived as larger where the lines are more compressed. We tested the hypothesis that a horizontal stimulus presented in a space perceived as larger will produce faster RTs by asking forty-four healthy subjects to respond as quickly as possible to lateralized stimuli (horizontal bars, vertical bars and circles) presented on different backgrounds (control condition: evenly spaced vertical lines or an empty space; illusory conditions: vertical lines progressively compressed to the right or the left). Subjects' RTs were reliably faster for horizontal stimuli presented on the space perceived as larger than on the space perceived as smaller. To verify that this effect was actually due to a size illusion, the same subjects were asked to adjust the size of the stimuli presented on the same backgrounds as to make them equal to a reference stimulus. For horizontal stimuli, subjects produced adjustments in accordance with the predicted effect of the illusion. Together, these data show that the OKI produces a distortion of space that extends to stimuli placed in front of it and that RTs are influenced by the perceived and not the physical size of the stimuli. Implications for neural bases of illusions and for spatial neglect are discussed. PMID- 22311469 TI - Response to comment on: Exp Brain Res. 2011 May 5th. Transcranial magnetic stimulation of macaque frontal eye fields decreases saccadic reaction time. Pierre Pouget PhD, Nicolas Wattiez MSc and Antoni Valero-Cabre MDPhD. PMID- 22311470 TI - GAS1 induces cell death through an intrinsic apoptotic pathway. AB - Growth Arrest Specific 1 (GAS1) is a protein expressed when cells are arrested and during development. When ectopically expressed, GAS1 induces cell arrest and apoptosis of different cell lines, and we have previously demonstrated that the apoptotic process set off by GAS1 is caused by its capacity inhibiting the GDNF mediated intracellular survival signaling. In the present work, we have dissected the molecular pathway leading to cell death. We employed the SH-SY5Y human neuroblastoma cell line that expresses GAS1 when deprived of serum. We observed, as we have previously described, that the presence of GAS1 reduces RET phosphorylation and inhibits the activation of AKT. We have now determined that the presence of GAS1 also triggers the dephosphorylation of BAD, which, in turn, provokes the release of Cytochrome-c from the mitochondria to the cytosol activating caspase-9, prompting the activity of caspase-3 and resulting in apoptosis of the cells. The apoptotic process is intrinsic, because there is no activation of caspase-8, thus this is consistent with apoptosis induced by the lack of trophic support. Interestingly, in cells where GAS1 has been silenced there is a significant delay in the onset of apoptosis. PMID- 22311471 TI - Molecular mechanisms of apoptosis induction by 2-dodecylcyclobutanone, a radiolytic product of palmitic acid, in human lymphoma U937 cells. AB - The irradiation of fat-containing food forms 2-dodecylcyclobutanone (2-DCB) from palmitic acid (PA). In this study, we investigated whether 2-DCB and PA induce apoptosis in human lymphoma U937 cells. We found that cell viability decreased by 2-DCB and apoptosis was induced by 2-DCB and PA. 2-DCB and PA significantly enhanced the formation of intracellular reactive oxygen species (ROS). Apoptosis induced by 2-DCB and PA was strongly prevented by an antioxidant, N-acetyl-L: cysteine. The treatment with 2-DCB and PA resulted in the loss of mitochondrial membrane potential, and Fas, caspase-8 and caspase-3 activation. Pretreatment with a pan-caspase inhibitor (z-VAD) significantly inhibited apoptosis induced by 2-DCB and PA. Moreover, 2-DCB and PA also induced Bax up-regulation, the reduction in Bcl-2 expression level, Bid cleavage and the release of cytochrome c from the mitochondria to the cytosol. In addition, an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) was observed after the treatment with 2-DCB and PA. Our results indicated that intracellular ROS generation, the modulation of the Fas-mitochondrion-caspase-dependent pathway and the increase in [Ca(2+)](i) involved in apoptosis are induced by 2-DCB and PA in U937 cells. PMID- 22311472 TI - High cytosolic free calcium level signals apoptosis through mitochondria-caspase mediated pathway in rat eggs cultured in vitro. AB - The present study was aimed to find out whether an increase of cytosolic free calcium level induces egg apoptosis through mitochondria-caspase mediated pathway. To increase cytosolic free calcium level and morphological apoptotic changes, ovulated eggs were cultured in Ca(2+)/Mg(2+) free media-199 with or without various concentrations of calcium ionophore (0.5, 1, 2, 3, 4 MUM) for 3 h in vitro. The morphological apoptotic changes, cytosolic free calcium level, hydrogen peroxide (H(2)O(2)) concentration, catalase activity, cytochrome c concentration, caspase-9 and caspase-3 activities and DNA fragmentation were analyzed. Calcium ionophore induced morphological apoptotic features in a concentration-dependent manner followed by degeneration at higher concentrations (3 and 4 MUM). Calcium ionophore increased cytosolic free calcium level, induced generation of hydrogen peroxide (H(2)O(2)) and inhibited catalase activity in treated eggs. The increased H(2)O(2) concentration was associated with increased cytochrome c concentration, caspase-9 and caspase-3 activities that resulted in the induction of morphological features characteristic of egg apoptosis. The increased caspase-3 activity finally induced DNA fragmentation as evidenced by TUNEL positive staining in calcium ionophore-treated eggs. These findings suggest that high cytosolic free calcium level induces generation of H(2)O(2) that leads to egg apoptosis through mitochondria-caspase mediated pathway. PMID- 22311473 TI - Controlled synthesis of 3D multi-compartmental particles with centrifuge-based microdroplet formation from a multi-barrelled capillary. AB - Controlled synthesis of micro multi-compartmental particles using a centrifuge droplet shooting device (CDSD) is reported. Sodium alginate solutions introduced in a multi-barreled capillary form droplets at the capillary orifice under ultrahigh gravity and gelify in a CaCl(2) solution. The size, shape, and compartmentalization of the particles are controlled. Co-encapsulation of Jurkat cells and magnetic colloids into Janus particles is demonstrated. The Janus particles present sensitive reaction toward magnetic fields, while the viability of the encapsulated cells is 91%. PMID- 22311474 TI - Emerging worldviews: the supplicate order-invocation of the sacred. AB - Approaches to supplication, such as faith and single-minded devotion to an ultimate value or deity, are proposed to constitute the human interface between the manifest and the unmanifest. A reciprocal, resonant interchange between the unmanifest and human summoning of the holy can bring the sacred to expression in cultural forms and personal experience. Addressing the boundaries between the human and the divine, this paper presents a cross-cultural model for spiritual supplication. This model utilizes the anthropological term ritual frame and provides an integrative worldview with which to examine the dynamics of sacred contact and invocation. This suggests that supplication is the universal and fundamental human orientation to invoke the reception of profound healings, as well as spiritual blessings, cross-cultural understandings and innumerable gifts of creativity. PMID- 22311476 TI - Antibiotic resistance patterns of Salmonella and Escherichia coli in the groundwater of Cyprus. AB - In addition to diet-based vectors of disease, the contribution of water-borne zoonotic agents to gastrointestinal illnesses may be significant, but this has yet to be investigated for Cyprus. Our main objective was to evaluate antibiotic resistance patterns of Salmonella and Escherichia coli in groundwater samples collected at confined animal feeding operations. This is the first report on the occurrence of antibiotic-resistant Salmonella and E. coli strains in the groundwater of Cyprus. Most of Salmonella isolates belonged to the subgroup enterica, whereas none of the E. coli isolates expressed the verotoxin-encoding gene. Out of 27 isolated Salmonella strains, nearly half of them were resistant to at least one or more antibiotic, whereas the highest resistance was exhibited by sulphamethoxazole (85%), followed by streptomycin (39%), and tetracycline (31%). For the E. coli isolates, nearly a third of them showed resistance to at least one antibiotic, whereas the selection of antibiotic resistance was equal among sulphamethoxazole, tetracycline and streptomycin (20%). This study demonstrated that Salmonella and E. coli in groundwater could pose a public health risk via oral ingestion of contaminated water. Best management practices are needed for overexploited groundwater supplies of rural areas, minimizing human exposure to antibiotic-resistant pathogens. PMID- 22311475 TI - The spiritual needs and resources of hospitalized primary care patients. AB - Previous studies have recognized the importance of hospitalized primary care patients' spiritual issues and needs. The sources patients consult to address these spiritual issues, including the role of their attending physician, have been largely unstudied. We sought to study patients' internal and external resources for addressing spiritual questions, while also exploring the physician's role in providing spiritual care. Our multicenter observational study evaluated 326 inpatients admitted to primary care physicians in four midwestern hospitals. We assessed how frequently these patients identified spiritual concerns during their hospitalization, the manner in which spiritual questions were addressed, patients' desires for spiritual interaction, and patient outcome measures associated with spiritual care. Nearly 30% of respondents (referred to as "R/S respondents") reported religious struggle or spiritual issues associated specifically with their hospitalization. Eight-three percent utilized internal religious coping for dealing with spiritual issues. Chaplains, clergy, or church members visited 54% of R/S respondents; 94% found those visits helpful. Family provided spiritual support to 45% of R/S respondents. Eight percent of R/S respondents desired, but only one patient actually received, spiritual interaction with their physician, even though 64% of these patients' physicians agreed that doctors should address spiritual issues with their patients. We conclude that inpatients quite commonly utilize internal resources and quite rarely utilize physicians for addressing their spiritual issues. Spiritual caregiving is well received and is primarily accomplished by professionals, dedicated laypersons, or family members. A significantly higher percentage of R/S patients desire spiritual interaction with their physician than those who actually receive it. PMID- 22311477 TI - Adenosine A1 receptor regulates osteoclast formation by altering TRAF6/TAK1 signaling. AB - Adenosine is an endogenous nucleoside that modulates many physiological processes through four receptor subtypes (A(1), A(2a), A(2b), A(3)). Previous work from our laboratory has uncovered a critical role for adenosine A(1) receptor (A(1) R) in osteoclastogenesis both in vivo and in vitro. Our current work focuses on understanding the details of how A(1) R modulates the receptor activator of NF kappaB ligand (RANKL)-induced signaling in osteoclastogenesis. Osteoclasts were generated from mouse bone marrow precursors in the presence of RANKL and macrophage-colony stimulating factor. A pharmacological antagonist of A(1) R (DPCPX) inhibited RANKL-induced osteoclast differentiation, including osteoclast specific genes (Acp5, MMP9, beta(3) Integrin, alpha(v) Integrin, and CTSK) and osteoclast-specific transcription factors such as c-fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1) expression in a dose-dependent manner. DPCPX also inhibited RANKL-induced activation of NF-kappaB and JNK/c-Jun but had little effect on other mitogen-activated protein kinases (p38 and Erk). Finally, immunoprecipitation analysis showed that blockade of A(1)R resulted in disruption of the association of tumor necrosis factor receptor-associated factor 6 (TRAF6) and transforming growth factor-beta-activated kinase 1 (TAK1), a signaling event that is important for activation of NF-kappaB and JNK, suggesting the participation of adenosine/A(1)R in early signaling of RANKL. Collectively, these data demonstrated an important role of adenosine, through A(1)R in RANKL-induced osteoclastogenesis. PMID- 22311478 TI - Chemiluminescence determination of sulphite using a cyclometalated iridium complex as chemiluminescence reagent. AB - A simple, fast and accurate chemiluminescence (CL) method for the determination of sulphite has been developed, based on its sensitizing effect on the CL reaction between a novel water-soluble iridium complex, [(dpci)2Ir(bvbbi)](PF6) (dpci = 3,4-diphenylcinnoline; bvbbi = N,N'-bivinylester-(1)H,(1')H-[2,2'] bibenzimidazole) and cerium(IV). Under the optimal experimental conditions, the increased CL response was linear, with the concentration of sulphite over the range 5.0 * 10(-7)-5.0 * 10(-4) mol/L. The detection limit of the method was 1.6 * 10(-7) mol/L, with a relative standard deviation (RSD) of 2.7% for nine repetitive determination of 1.0 * 10(-4) mol/L sulphite. The method was successfully applied to the quantitative analysis of sulphite in sugar samples. The possible reaction mechanism of sulphite on the [(dpci)2Ir(bvbbi)](PF6) cerium(IV) system is also briefly discussed. PMID- 22311479 TI - Developmental pattern of Ginkgo biloba levopimaradiene synthase (GbLPS) as probed by promoter analysis in Arabidopsis thaliana. AB - Levopimaradiene synthase (GbLPS) of Ginkgo biloba catalyzes the first committed step in ginkgolide biosynthesis by converting geranylgeranyl diphosphate into levopimaradiene, which subsequently undergoes complex oxidation step and rearrangement of carbon skeleton, leading to formation of ginkgolides. To assess the organ-specificity and developmental characteristics of GbLPS expression, the GbLPS promoter-driven GUS expression in transgenic Arabidopsis was studied. Histological analysis of the transgenic Arabidopsis plant showed that the GUS accumulation was mainly localized in the epidermis of leaves, phloem of the shoots, ovaries and stamens of flowers, and vasculature of roots. These observations correlate with the occurrence of LPS transcripts in roots and male strobili of G. biloba. Treatment of methyl jasmonate on the transformant exhibited significant upregulation of the reporter gene in the roots with little change in leaves and flowers. The present findings support biosynthesis of ginkgolide in the roots of Ginkgo plant and suggest translocation occurs through the phloem. PMID- 22311480 TI - [Novel compound heterozygous mutations of TGM1 gene identified in a Chinese collodion baby]. AB - OBJECTIVE: To identify potential mutations in a Chinese collodion baby. METHODS: The patient was investigated clinically. DNA was extracted from peripheral blood of the baby and his parents. All coding exons(exons 2-15) and splicing sites of transglutaminase 1(TGM1) were amplified by polymerase chain reaction (PCR). Mutation detection was performed by directed sequencing of the PCR products. A total of 100 healthy unrelated subjects were used as controls. Haplotypes were constructed with microsatellites flanking the locus, and TGM1 genotypes of the family were used to determine parental origins of the mutations. CLUSTAL X (1.81) was employed to analyze cross-species conservation of the mutant protein sequence. RESULTS: The boy was found to be a compound heterozygote for two novel mutations: c.420A>G (I140M) from his father and c.832G>A (G278R) from his mother, with the former occurring in the transglutaminase N domain and the latter between transglutaminase N and transglutaminase-like domains. Both mutations were absent from the control subjects. CONCLUSION: The boy's condition was caused by two novel compound heterozygous mutations of c.420A>G and c.832G>A of TGM1. Author's results may provide new clues for molecular diagnosis of this disease. PMID- 22311481 TI - [Identification of a novel PHOX2A gene mutation in a Chinese family with congenital fibrosis of extraocular muscles type 2]. AB - OBJECTIVE: To investigate potential mutation of PHOX2A (or ARIX) gene in a Chinese family affected with congenital fibrosis of extraocular muscles tyep 2 (CFEOM2). METHODS: Genomic DNA was obtained from affected and unaffected members of the family. With an ABI PRSIM Linkage Mapping Set-MD10 kit, selected markers flanking the PHOX2A locus were used for linkage analysis. Exons of PHOX2 gene were amplified and sequenced. A total of 100 normal subjects were recruited as controls. RESULTS: Genetic linkage was found at 11q13 between D11S4151 and D11S1320 and the PHOX2A gene. DNA sequencing has identified a heterozygous mutation in the exon 2 of the gene (227T to G, N76K). The same mutation was not found in the unaffected and 100 normal controls. CONCLUSION: A mutation of the PHOX2A gene 227T to G is responsible for the onset of congenital fibrosis of extraocular muscles type 2 in this Chinese family. PMID- 22311482 TI - [Application of SNPstream for medical genetics research]. AB - OBJECTIVE: To introduce the principle, procedure, efficacy and application of SNPstream genotyping technology. METHODS: Genotyping results of 152 SNPs were used to analyze the feasibility, call rate and accuracy of SNPstream technology. RESULTS: For the 152 selected SNPs, 122 SNPs can be genotyped with SNPstream, for which 116 SNPs were successfully genotyped. Replication study showed that the repeatability of genotyping is 99%. When the allele cluster was clear, the accuracy can reach 100%. But when the allele cluster was obscure, the accuracy was only 93.8%. CONCLUSION: SNPstream technology has the advantages of high accuracy, flexible throughput, and high cost performance, and may have a wide application for medical genetics research. PMID- 22311483 TI - [Identification of a TTR gene mutation in a family with hereditary vitreous amyloidosis]. AB - OBJECTIVE: To study the disease gene in a family with hereditary vitreous amyloidosis. METHODS: A family with hereditary vitreous amyloidosis was investigated. Blood samples were collected from 4 members of this family including 3 patients and 1 asymptomatic individual. Genomic DNA was extracted from peripheral blood sample and subjected to amplification of 4 exons of transthyretin (TTR) gene. The PCR products were purified and subjected to direct sequencing. A total of 150 unrelated individuals were used as controls. RESULTS: A heterozygous mutation G to C at codon 103 in exon 3 of TTR gene (Gly103Arg) was detected in all 4 members of the family but not in the unrelated controls. CONCLUSION: The heterozygous Gly103Arg mutation of TTR gene may be related to the development of hereditary vitreous amyloidosis in this family. PMID- 22311484 TI - [Detection for trinucleotide repeats in myotonic dystrophy type 1]. AB - OBJECTIVE: To establish an efficient method which can be easily used for detecting CTG trinucleotide repeats in myotonic dystrophy type 1 (DM1). METHODS: Tri-primer polymerase chain reaction (TP-PCR) combined with electropherogram was used to detect CTG repeats in the 3'-untranslated region of DMPK gene. Twenty non related DM1 patients and 24 healthy controls were selected. RESULTS: All patients were found to have carried pathologic alleles containing more than 100 CTG repeats, while the healthy controls have carried 5-37 CTG repeats. CONCLUSION: TP PCR combined with electropherograms may provide a highly sensitive, specific and accurate method which is less time-consuming and easier to perform for the detection of pathologic alleles in DM1 patients. PMID- 22311485 TI - [Effect of dihydroartemisinin on the expression of BCR/ABL fusion gene in leukemia K562 cells]. AB - OBJECTIVE: To investigate the effect of dihydroartemisinin (DHA) on the BCR/ABL fusion gene in leukemia K562 cell. METHODS: K562 cells were cultured in vitro. The rate of proliferation inhibition of cells treated with various concentrations of DHA were determined by using [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide] (MTT) method. Expression of BCR/ABL fusion gene was analyzed by reverse transcription(RT-PCR) before and after DHA treatment. Apoptosis of K562 cells was detected by flow cytometry. RESULTS: The growth of K562 cells was inhibited when the concentrations of DHA were 10-160 umol/L. With the added dose of DHA, the growth inhibition was remarkable, with the rate of inhibition risen from 52.76% to 94.65%. The expression of BCR/ABL fusion gene, as detected by RT-PCR after incubating the K562 cells with 20 umol/L DHA, measured as DeltaCt = 4.45 +/- 0.25 after 12 h and DeltaCt = 5.23 +/- 0.21 after 24 h, which was significantly lower compared with that of the control ( DeltaCt = 4.23 +/- 0.21, P < 0.05). CONCLUSION: DHA can inhibit the proliferation of leukemia K562 cells and facilitate the induction of apoptosis by downregulating the expression of BCR/ABL fusion gene. PMID- 22311486 TI - [Effects of CYP1A1 and GSTM1 gene polymorphisms and BPDE-DNA adducts on lung cancer]. AB - OBJECTIVE: To investigate the effect of CYP1A1 and GSTM1 genetic polymorphisms and BPDE-DNA adducts on lung tumorigenesis. METHODS: The case control study has included 200 cases of lung cancer and 200 controls. DNA was extracted from blood samples of all subjects. The genotype of both CYP1A1 and GSTM1 were detected with PCR-based restriction fragment length polymorphisms (PCR-RELP). BPDE-DNA adducts were detected with competitive ELISA. RESULTS: CYP1A1 mutant genotype and GSTM1 null genotype with smoke has increased the risk of lung cancer, with OR being 2.406(1.321-4.382), 2.755(1.470-5.163), respectively. The level of BPDE-DNA adducts in patients was greater than control, and the adduct level in ever smokers was higher than never smokers, the difference was statistically significant (P= 0.0252). GSTM1 null genotype individuals with BPDE-DNA level higher than 5 adducts/10(8) nucleotide have increased risk of lung cancer (OR= 1.988, 95%CI: 1.011-3.912). Compared with never smokers with CYP1A1 wild genotype, smokers with CYP1A1 mutation genotype had an increased risk of forming a higher level of DNA adducts (P= 0.0459). Smokers with GSTM1 null genotype formed more DNA adducts compared with never smokers with GSTM1 functional genotype (OR = 2.432, 95% CI: 1.072-4.517). CONCLUSION: GSTM1 null genotype with higher level DNA adducts may increase the risk of lung cancer. DNA adducts form easier in smokers with CYP1A1 mutation genotype and GSTM1 null genotype, which in turn may influence lung tumorigenesis. PMID- 22311487 TI - [A study on paternity testing with 96 autosomal SNPs]. AB - OBJECTIVE: To explore the feasibility of applying autosomal single nucleotide polymorphisms (SNPs) on parentage testing. METHODS: All SNP genotyping results of HapMap (r27) were downloaded from the website. With self-made computer programs, SNPs were extracted when their minor allele frequency (MAF) were >= 0.30 among all of the 11 HapMap populations. Ninety-six SNPs were chosen and integrated into the Illumina Goldengate bead arrays on the condition that no linkage disequilibrium was found between them. Three father-child-mother trios (9 samples in total) were tested with the arrays. Cumulative paternity index (CPI) was then calculated and compared with genotyping results using 15 short tandem repeats (STRs)(Identifiler(TM)). RESULTS: Family 1 was found to have nine SNPs or seven STRs that did not conform to the Mendelian laws, Family 2 had 13 such SNPs or seven STRs, and Family 3 only had one such SNP but no STR. For Family 3, when all of the 96 SNPs were used in combine, the CPI was 1207, which had contrasted with the CPI by the 15 STRs, i.e., 355 869. CONCLUSION: When applied to paternity testing, the paternity exclusion (PE) value for a SNP is usually less than 1/3 of that of a STR. The proportion of SNPs not comforming to the Mendelian laws for the tested SNPs may not be as high as that of inconsistent STRs over all tested STRs. Because of the low mutation rate of a SNP, the CPI will be greatly reduced even if one SNP did not conform to the Mendelian laws. Therefore, highly accurate testing methods are required to reduce artificial errors when applying SNPs for paternity testing. PMID- 22311488 TI - [Limitation of PCR-RFLP method for the detection of genetic mutations in spinal muscular atrophy]. AB - OBJECTIVE: To explore the applicability and limitation of PCR-restriction fragment length polymorphism (PCR-RFLP) method for genetic diagnosis of spinal muscular atrophy (SMA). METHODS: PCR-RFLP was applied to detect potential deletion in exons 7 and 8 of SMN1 gene in 935 suspected cases with SMA. Multiplex ligation-dependent probe amplification(MLPA) was carried out to analyze dosage alteration of SMN1 gene in 339 of such cases. To confirm the accuracy of PCR-RFLP method for homozygous and heterozygous deletions detection, the consistency of PCR-RFLP and MLPA results were assessed with a Pearson Chi-square test. RESULTS: Homozygous deletion of exon 7 of SMN1 was detected in 590 suspected cases. The rate of diagnosis was therefore 63.1% (590/935). For the 339 suspected cases, PCR RFLP and MLPA respectively identified 194 and 196 homozygous deletions in the exon 7 of SMN1 gene, suggesting a good consistency (98.9%)(Chi-square = 0.2, P = 0.88). However, only 4 of 339 cases was found to carry a heterozygous deletion of SMN1 exon 7 by PCR-RFLP, in contrast with 17 detected by MLPA. The consistency only reached 23.5%, for which statistical significance was detected (Chi-square = 8.29, P< 0.01). CONCLUSION: Although PCR-RFLP is a simple, specific and efficient method for SMA diagnosis, it has obvious limitation for the diagnosis of 5%-10% SMA patients who have carried a compound heterozygous mutation. PMID- 22311489 TI - [Progress in genetic and epigenetic research on in-stent restenosis after percutaneous coronary interventions]. AB - Coronary heart disease is one of the most important causes of death in human, and consumes vast medical resources. Percutaneous coronary intervention (PCI) has been a significant breakthrough for its treatment. However, clinical application has been hampered by in-stent restenosis (ISR). Although drug eluting stent (DES) has reduced the occurrence of restenosis, incidence of ISR is still about 5% to 10%. The main reasons for restenosis after PCI are hyperplasia of vascular endothelial cells and smooth muscle cell migration. The exact mechanism of personalized differences in restenosis is not clear yet, but there may be a variety of risk factors. In addition to aging, smoking and diabetes, an increasing number of studies have found that genetic and epigenetic factors play an important role in ISR. In this article, authors have reviewed genetic and epigenetic factors on the progression of ISR, which may help to determine the genetic risk factors in patients with ISR after PCI. PMID- 22311490 TI - [Detecting Down syndrome with a novel dual-color competitive quantitative fluorescent polymerase chain reaction method]. AB - OBJECTIVE: To develop a rapid method for the detection of Down syndrome (DS) using dual-color competitive quantitative fluorescent polymerase chain reaction (DCC-QF-PCR), and to assess its feasibility for the prenatal diagnosis of Down syndrome. METHODS: DNA was extracted from peripheral blood of 30 DS patients and 60 normal men, common primers for DSCR and USC2 genes and respective TaqMan probes were designed and synthesized. The results of DCC-QF-PCR were compared with those of QF-PCR which measured the ratio between DSCR and GAPDH. Forty-six amniotic fluid samples were assayed with DCC-QF-PCR. The results were compared with that of karyotyping. Monoclone fragments for DSCR and USC2 genes were obtained from direct cloning of PCR products. DCC-QF-PCR was carried out using different DNA ratios of DSCR and USC2 as the template. The dosage ratio between DSCR and USC2 was calculated. RESULTS: The gene dosage ratio of the DS patients was 1.41-1.74, which was significantly higher than that of normal men (0.93 1.15). The dosage ratio range of DSCR and GAPDH by QF-PCR was comparatively greater than that of DSCR and USC2. Three samples were diagnosed as DS, which was in good agreement with that of karyotyping analysis. There was no significant difference between the gene dosage ratio from DCC-QF-PCR and that of predetermined (P>0.05). CONCLUSION: DCC-QF-PCR is an accurate, rapid, and low cost method, which only requires tiny amount of sample and therefore has broad application in the genetic and prenatal diagnosis. PMID- 22311491 TI - [Dandy-walker syndrome and microdeletions on chromosome 7]. AB - OBJECTIVE: To investigate genetic etiology of Dandy-Walker syndrome with array based comparative genomic hybridization (array-CGH). METHODS: Eight fetuses with Dandy-Walker malformations but normal karyotypes by conventional cytogenetic technique were selected. DNA samples were extracted and hybridized with Affymetrix cytogenetic 2.7 M arrays by following the manufacturer's standard protocol. The data were analyzed by special software packages. RESULTS: By using array-CGH technique, common deletions and duplication on chromosome 7p21.3 were identified in three cases, within which were central nervous system disease associated genes NDUFA4 and PHF14. CONCLUSION: Copy number variations (CNVs) of chromosome 7p21.3 region are associated with Dandy-Walker malformations which may be due to haploinsufficiency or overexpression of NDUFA4 and PHF14 genes. PMID- 22311492 TI - [Detection of 9p partial trisomy using array-based comparative genomic hybridization]. AB - OBJECTIVE: To detect chromosomal aberrations in a child with developmental delay and speech and language disorders in order to explore the underlying genetic causes of congenital malformation, and to investigate the feasibility of array based comparative genomic hybridization (array-CGH) for molecular genetic diagnosis. METHODS: G-banding and array-CGH were applied to characterize the genetic abnormality in the three family members. RESULTS: G-banding analysis revealed the affected child and the healthy mother are both carriers of inv(9)(p13q13), while the child has carried a chromosome fragment derived from chromosome 13. Array-CGH analysis indicated the derivative chromosome fragment has originated from 9p with breakpoints at around 9p13.1-p24.3. CONCLUSION: Trisomy 9p13.1-p24.3 may be the cause of congenital malformation in the child. For its high resolution and high accuracy, array-CGH is a powerful tool for genetic analysis. PMID- 22311493 TI - [Association between -14 bp and ZNF polymorphisms of ABCA1 gene promoter and high density lipoprotein cholesterol level and cardiovascular disease]. AB - OBJECTIVE: To investigate the association between polymorphisms at -14 bp and zinc finger protein(ZNF) sites of ATP-binding cassette transporter A1 (ABCA1) gene promotor and high density lipoprotein-cholesterol (HDL-C) level and coronary heart disease (CHD). METHODS: Polymorphisms of Bme13901 restriction site at -14 bp and an insertion/deletion site of ACCCC in variable number of tandem repeats zinc finger protein(VNTR-ZNF) of ABCA1 gene were detected using PCR in 260 CHD patients and 220 healthy subjects from a Chinese population in Tianjin. RESULTS: CT genotype was most common in both groups with no differences found in between (P> 0.05). No differences were found in the frequencies of the rare T allele for 14 bp (P> 0.05). For the -14 bp site, subjects with CT/TT genotype had a lower serum mean concentration of HDL-C compared with those with the CC genotype (P< 0.05). Genotypic frequencies of VNTR-ZNF were 6.2% for the inserted form, 43.8% for the deleted form and 50.0% for the inserted/deleted form. No significant difference was found in the distribution of allele and genotype, or in the levels of HDL-C between the two groups (P> 0.05). CONCLUSION: The genotypes at -14 bp of ABCA1 gene are associated with the plasma level of HDL-C. HDL-C levels in T allele carriers were significantly lower (P< 0.05). No association was found between variations in ABCA1 VNTR-ZNF and plasma levels of HDL-C, or between the ABCA1 -14 bp and VNTR-ZNF polymorphisms and susceptibility for CHD. PMID- 22311494 TI - [Association between matrix metalloproteinase-8 -799C/T polymorphism and instability of carotid plaque]. AB - OBJECTIVE: To investigate the association between a -799C/T polymorphism in the promotor region of matrix metalloproteinase-8 (MMP-8) gene and instability of carotid plaque in Chinese Han population. METHODS: A total of 451 acute infarction patients from the Department of Neurology of Taizhou Hospital were divided into carotid vulnerable plaque group and carotid stable plaque group according to the results of carotid B-mode ultrasonography. Serum MMP -8 level was measured by the means of enzyme-linked immunosorbent assay (ELISA). At the same time, the MMP-8 -799C/T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Serum level of MMP-8 in the carotid vulnerable plaque group was higher than that in the carotid stable plaque group (t= 2.894, P= 0.004). The genotype distribution of -799C/T polymorphism between the two groups was significantly different (Chi-square = 13.65, P= 0.000). Serum level of MMP-8 in patients with TT genotype was higher than that in patients with CC genotype (t= 3.141, P= 0.001). CONCLUSION: The present study suggested that serum level of MMP-8 and the -799C/T polymorphism of MMP-8 gene are associated with carotid vulnerable plaque in Chinese Han population, and the T allele may be a predictor for the susceptibility of carotid vulnerable plaque. PMID- 22311495 TI - [Characteristics and outcome of chromosomal abnormalities in Ph negative cells of chronic myelogenous leukemia patients treated with tyrosine kinase inhibitors]. AB - OBJECTIVE: To investigate cytogenetic features and outcome of chromosomal abnormalities in Philadelphia negative cells (Ph(-)CAs) of chronic myelogenous leukemia (CML) patients treated with tyrosine kinase inhibitors. METHODS: Clinical and laboratory data of 15 CML patients in which Ph(-)CAs occurred after tyrosine kinase inhibitors therapy were collected and analyzed. RESULTS: Of 15 cases with Ph(-)CAs, 12 patients were treated with imatinib, 2 were treated with dasatinib and 1 was treated with bosutinib. + 8 was the most common abnormality in Ph(-)CAs, which accounted for 46.7% of all. Ph(-)CAs usually occurred when Ph(+)cells decreased or disappeared due to tyrosine kinase inhibitors therapy. The average time for the appearance of Ph(-)CAs was 11.1 months (1-28 months). In 7 patients, the Ph(-)CAs have disappeared in 10.9 months (3-24 months). In such patients, no myelodysplastic syndrome or acute leukemia was observed. One patient has progressed to acute monocytic leukemia with Ph(+)cells. All remaining patients have achieved bone morrow remission, among which 11 patients achieved complete cytogenic response and 4 patients even achieved complete molecular response. CONCLUSION: The majority of Ph(-)CAs developed in CML patients are transient in nature. They may develop following imatinib, dasatinib or bosutinib therapy but do not interfere with the therapeutic effects of tyrosine kinase inhibitors. PMID- 22311496 TI - [Effect of CYP11B2 gene -344T/C polymorphism on renin-angiotensin-aldosterone system activity and blood pressure response to hydrochlorothiazide]. AB - OBJECTIVE: To evaluate the effect of CYP11B2 gene -344T/C polymorphism on renin angiotensin-aldosterone system (RAAS) activity and blood pressure in response to hydrochlorothiazide (HCTZ) treatment in Han Chinese patients with essential hypertension. METHODS: Eight hundred and twenty-nine patients with mild/moderate essential hypertensive were enrolled. All subjects had their antihypertensive medications withdrawn. After two weeks of wash-out period with placebo, each patient was given 12.5 mg of HCTZ per day for the next six weeks. Physical, biochemical measurements, and the activity of RAAS were taken at the end of the wash-out period (baseline) and 6-week diuretic therapy period. Changes in systolic and diastolic blood pressure were analyzed for association with interaction between genotypes at CYP11B2 -344T/C polymorphism and gender. RESULTS: A total of 776 patients completed the study. 17.5% of subjects have achieved blood pressure normalization after six weeks treatment. For male patients, the aldosterone level with CC genotype was significantly higher than that of those with TT or TC genotype. Following the HCTZ treatment, the blood pressure response in patients with CC genotype was less obvious than that in others, whilst the increase of aldosterone level was greater. For female patients, no association was found between CYP11B2 -344T/C polymorphism and aldosterone level. Following the HCTZ treatment, the blood pressure response in patients with CC genotype was greater than others, whilst the increase of aldosterone activity was less apparent. CONCLUSION: In males, the -344T/C polymorphism of CYP11B2 gene is associated with aldosterone level, and the change of aldosterone level was greater, the blood pressure response was weaker after HCTZ treatment. In females, there was no association between this polymorphism and aldosterone level. The change of aldosterone level and blood pressure response to HCTZ were different from that in males. PMID- 22311497 TI - [Association of 1233A/G polymorphism of angiopoietin-2 gene with type 2 diabetes mellitus and diabetic nephropathy]. AB - OBJECTIVE: To investigate the association between single nucleotide polymorphisms (SNP) of angiopoietin-2 (Ang-2) gene and type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). METHODS: Genotype and allele frequency of Ang-2 were detected by amplification refractory mutation system-PCR(ARMS-PCR) in 221 cases with T2DM and 104 normal controls. Monocyte chemoattractant protein-1(MCP-1) was measured by ELISA. DN patients were divided into three groups according to urinary albumin excretion rates (UAER), i.e. DN0: UAER < 30 mg/24 h, DN1: UAER 30 300 mg/24 h and DN2: UAER > 300 mg/24 h. RESULTS: Statistics showed: (1) Genotype frequencies and allele frequencies in Ang-2 1233A/G had significant difference but not Ang-2 759T/G and 1078A/G; (2) Comparing with those with genotype AA, the relative risk of genotype (AG+ GG) suffered from T2DM and DN were 2.265 fold (OR= 2.265, 95% CI: 1.223-1.402, P= 0.031), 1.789 fold (OR= 1.789, 95% CI: 0.889 1.021, P= 0.012), respectively; (3) The onset of DN was related to Ang-2 1233A/G allele G (r= 1.321, OR= 1.427, 95% CI: 2.324-4.177, P= 0.034). CONCLUSION: Ang-2 1233A/G polymorphism may be associated with T2DM and involved in onset and development of DN. PMID- 22311498 TI - [Genetic analysis of a supernumerary derivative chromosome 15]. AB - OBJECTIVE: To detect and analyze a supernumerary derivative chromosome 15 with combined cytogenetic and molecular techniques, and to discuss the correlation between genomic copy number variations (CNVs) and clinical phenotypes. METHODS: G banded chromosome analysis and multiplex ligation-dependent probe amplification (MLPA) were carried out. The whole genome of the patient was also analyzed with array-comparative genome hybridization(array-CGH). RESULTS: G-banding analysis indicated that the patient has a karyotype of 47, XY, + mar, with the supernumerary chromsome derived from 15q11-13 region spanning 9.8 Mb from locus 20477397 to 30298155. CONCLUSION: CNVs of 15q11-13 are associated with mental retardation, language development delay and autistic disorder. Conventional cytogenetic analysis with array-CGH may provide a platform for accurate detection of chromosomal aberrations, which can faciliate the study of genome rearrangement underlying various diseases. PMID- 22311499 TI - [Genetic polymorphisms of six Y chromosome short tandem repeat loci in Chinese Korean ethnic group]. AB - OBJECTIVE: To determine the allelic sequences and genetic polymorphism of six short tandem repeats (STRs) loci on Y chromosome, including DYS441, DYS442, DYS443, DYS444, DYS445 and DYS446 in Chinese Korean ethnic males from Yanbian region of Jilin province, China, and to construct a preliminary database. METHODS: Allele frequencies of the six STR loci in 205 Chinese Korean ethnic individuals were analyzed by multiplex polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE). RESULTS: Respectively, 8, 7, 7, 5, 6 and 9 alleles were detected for each of the locus. Together they have formed 151 haplotypes, with a diversity of 0.9937. CONCLUSION: The six STR loci included in this study were found to be highly polymorphic, and may provide useful markers for genetic analysis. PMID- 22311500 TI - [Analysis of allele frequencies of HLA-DRB1*12:01:01G and HLA-DRB1*14:01:01G groups]. AB - OBJECTIVE: To discriminate and analyze the relative frequencies of alleles in HLA DRB1*12:01:01G(HLA-DRB1*12:01:01/12:06/12:10/12:17) and HLA-DRB1*14:01:01G (DRB1*14:01:01/14:54) groups and assess their associations with HLA-DRB3 and HLA DQB1 loci. METHODS: A total of 115 DNA samples previously typed as HLA DRB1*12:01:01G and 108 samples from HLA-DRB1*14:01:01G were selected. DNA sequences for exons 1 to 3 of the HLA-DRB1 locus were analyzed for HLA DRB1*12:01:01G, and exons 2 to 3 were analyzed for HLA-DRB1*14:01:01G by polymerase chain reaction sequence-based typing (PCR-SBT). Genotyping of HLA-DRB3 and HLA-DQB1 were achieved by PCR-SBT. RESULTS: Among 115 samples previously typed as HLA-DRB1*12:01:01G, 101 (87.8%) were confirmed as HLA-DRB1*12:01:01 and 14 (12.2%) were HLA-DRB1*12:10, but HLA-DRB1*12:06 and HLA-DRB1*12:17 alleles were not identified. For 108 samples previously typed as HLA-DRB1*14:01:01G, all were typed as HLA-DRB1*14:54. HLA-DRB1*12:01:01 was linked with HLA-DRB3*01:01:02 and HLA-DQB1*03:01, while HLA-DRB1*12:10 was strongly linked with HLA DRB3*02:02:01 and HLA-DQB1*03:01. HLA-DRB1*14:54 was strongly linked with HLA DRB3*02:02:01 and two different HLA-DQB1*05:02, *05:03 alleles. CONCLUSION: HLA DRB1*12:01:01 was more prevalent than HLA-DRB1*12:10 in the HLA-DRB1*12:01:01G group, and HLA-DRB1*14:54 was the dominant allele for HLA-DRB1*14:01:01G. PMID- 22311501 TI - [Identification and sequence analysis of a novel human leukocyte antigen allele B*54:09]. AB - OBJECTIVE: To identify a novel human leukocyte antigen(HLA) allele in Chinese population. METHODS: HLA typing was carried out with polymerase chain reaction sequence specific oligonucleotide probes (PCR-SSOP). The HLA-B exons 1-7 of the proband were amplified and the product was cloned using a TOPO TA cloning sequencing kit to separate the two alleles. Both strands of exons 2 and 3 of selected colonies were sequenced. Sequence-based typing (SBT) was used to identify and analyze the difference between the new allele and the closest matching HLA-B allele. RESULTS: HLA typing indicated a SSOP pattern which did not match with known HLA-B alleles. The results of the sequencing suggested the HLA-B alleles of the proband as B*59:01 and a novel allele. The HLA-B exon 3 sequence of the novel allele was different from any known alleles. This allele differs from the closest matching B*54:06 allele by 6 nucleotides, which included nt486 (G to C), nt527 (A to T), nt538 (T to C), nt539 (G to T), nt559 (C to A) and nt560 (T to C) in exon 3, resulting in substitutions of three amino acids including Glu to Val at codon 152, Trp to Leu at codon 156 and Leu to Thr at codon 163. CONCLUSION: A novel HLA-B allele has been identified and has been designated as HLA-B*54:09 by WHO Nomenclature Committee for Factors of the HLA System. PMID- 22311510 TI - [Description of poisoning reported in Marrakech-Tensift-Al Haouz region in Morocco between 1981 and 2008]. AB - In Morocco, the Marrakech-Tensift-Al Haouz region is one of the 16 regions most affected by poisoning. The aim of this study was to determine the epidemiological profile of poisoning recorded in the study region. A retrospective study of poisoning cases, declared between 1981 and 2008 in the Morocco Poison Control and Pharmacovigilance Center, was conducted. During the study period, 8517 poisoning cases were collected. The average age of patients was 22 +/- 15 years. The male/female sex ratio was 0.85. Food poisoning was the most reported in the region, with 26.6% of cases. Among the 2,779 patients for whom the outcome was known, 65 died, with lethality rate of 23.40/00. The maximum lethality rate was recorded among those poisoned by paraphenylenediamine (170.70/00). PMID- 22311511 TI - Calcineurin/NFAT signalling inhibits myeloid haematopoiesis. AB - Nuclear factor of activated T cells (NFAT) comprises a family of transcription factors that regulate T cell development, activation and differentiation. NFAT signalling can also mediate granulocyte and dendritic cell (DC) activation, but it is unknown whether NFAT influences their development from progenitors. Here, we report a novel role for calcineurin/NFAT signalling as a negative regulator of myeloid haematopoiesis. Reconstituting lethally irradiated mice with haematopoietic stem cells expressing an NFAT-inhibitory peptide resulted in enhanced development of the myeloid compartment. Culturing bone marrow cells in media supplemented with Flt3-L in the presence of the calcineurin/NFAT inhibitor Cyclosporin A increased numbers of differentiated DC. Global gene expression analysis of untreated DC and NFAT-inhibited DC revealed differential expression of transcripts that regulate cell cycle and apoptosis. In conclusion, these results provide evidence that calcineurin/NFAT signalling negatively regulates myeloid lineage development. The finding that inhibition of NFAT enhances myeloid development provides a novel insight into understanding how the treatment with drugs targeting calcineurin/NFAT signalling influence the homeostasis of the innate immune system. PMID- 22311512 TI - Considering the role of conditioning in sexual orientation. AB - The effects of learning on sexual orientation are rarely addressed in the literature. At the very least, such processes provide a means of elaborating upon orientation predispositions. Some aspects of our mates may inherently elicit a sexual response, but other attributes do so only after sexual experience with them. Animal research shows robust, direct effects of conditioning processes on partner preference with a few studies showing plasticity in preference for sex of partner. Descriptive research in humans suggests effects of experience on partner preference and, although experimental demonstrations of human sexual conditioning are neither numerous nor robust, sexual arousal is conditionable in women and men. With modern developments in learning theory (e.g., expectancy learning and evaluative conditioning), it seems appropriate to renew the investigation of contributions and limitations of conditioning processes to explaining how cues acquire erotic value and to attempt some integration between the sexual conditioning literature and research on sexual orientation or more generally sexual partner preference. PMID- 22311513 TI - Picobirnavirus infections: viral persistence and zoonotic potential. AB - Picobirnaviruses (PBVs) are small, non-enveloped, bisegmented double-stranded RNA genomic viruses of vertebrate hosts. Since their discovery in the late 1980s in clinical specimens from outbreaks of acute gastroenteritis in children, significant efforts have been made to investigate the role of PBV in diarrheic diseases. PBV has been detected in sporadic episodes of diarrhea as sole pathogen or coinfection as well as in outbreaks of acute gastroenteritis and in immunocompromised patients with diarrhea. However, PBV is frequently detected in non-diarrheic healthy hosts, and prolonged shedding has been observed in some individuals. Of interest, similar patterns of PBV infection have also been observed in pigs and other animal hosts. The increasing amount of PBV sequence data gathered from molecular epidemiological studies has evidenced a great sequence diversity of PBVs in various hosts and environmental samples. Importantly, evidence has been found for genetic relatedness between human and animal PBV strains, suggesting extant crossing points in the ecology and evolution of heterologous PBV strains. At present, no cell culture and animal model exists for PBVs. Well-structured epidemiological studies are still the only alternative to demonstrate the potential etiological role of PBVs in acute gastroenteritis or other diseases. This review aims to analyze the public health aspects of PBV infection, especially its possible association with zoonosis. PMID- 22311514 TI - cagA structural types of Helicobacter pylori strains isolated from patients with gastric carcinoma and chronic gastritis only. PMID- 22311515 TI - Pinch-off syndrome: a simple test is the best. PMID- 22311516 TI - Left ventricle outflow tract vegetation, embolism and troponin rise: an infective endocarditis case report. PMID- 22311517 TI - Responses of urinary N-telopeptide and renal calcium handling to PTH infusion after treatment with estrogen, raloxifene, and tamoxifen. AB - This prospective, randomized, placebo-controlled study investigated whether estrogen, tamoxifen, and raloxifene protect the skeleton from the acute catabolic effects of continuous PTH(1-34) infusion. It was infused over 24 h in 25 postmenopausal women both before and while on medication for 16-20 weeks (estrogen n = 7, raloxifene n = 5, tamoxifen n = 7, placebo n = 6). Blood and urine samples were collected at baseline and every 4 h during the PTH(1-34) infusion and analyzed for calcium homeostasis, bone remodeling, and specific cytokines. Data for the premedication PTH(1-34) infusions were pooled. During the premedication PTH(1-34) infusions, serum calcium and urine phosphorus increased, while serum phosphorus and urine calcium declined. Osteocalcin decreased (mean 18%), while urine NTX increased (mean 315%). Serum IL-6 increased 260%, but there were no other cytokine changes as a result of the PTH(1-34) infusion. On medication, the mean peak change in NTX with PTH(1-34) infusion was less (77, 59, and 31 nM/mM with raloxifene, tamoxifen, and estrogen, respectively). The reduction in urine calcium excretion was prolonged with each agent but only significantly with estrogen. There was no reduction in the IL-6 elevation induced by PTH(1-34) with any medication. The differential skeletal resorption response to PTH(1-34) infusion after the treatments may reflect different potencies of these agents or variability in interaction with the estrogen receptor. Renal calcium conservation and the blunted response of bone resorption to PTH(1-34) infusion may be mechanisms by which estrogen and estrogen agonist/antagonist agents preserve bone mass. PMID- 22311518 TI - Nitrogen-enriched core-shell structured Fe/Fe(3)C-C nanorods as advanced electrocatalysts for oxygen reduction reaction. AB - A cost-effective route for the preparation of Fe(3) C-based core-shell structured catalysts for oxygen reduction reactions was developed. The novel catalysts generated a much higher power density (i.e., three times higher at R(ex) of 1 Omega) than the Pt/C in microbial fuel cells. Furthermore, the N-Fe/Fe(3)C@C features an ultralow cost and excellent long-term stability suitable for mass production. PMID- 22311519 TI - Inflexible parents, inflexible kids: a 6-year longitudinal study of parenting style and the development of psychological flexibility in adolescents. AB - Parenting behaviors have been linked to children's self regulation, but it is less clear how they relate to adolescent psychological flexibility. Psychological flexibility is a broad construct that describes an individual's ability to respond appropriately to environmental demands and internal experiences in the service of their goals. We examined the longitudinal relationships between perceived parenting style and psychological flexibility among students at five Australian schools (N= 749) over 6 years, beginning in Grade 7 (50.3% female, mean age 12.39 years). Parenting style was measured in Grades 7 and 12, and psychological flexibility from Grade 9 through 12. Psychological flexibility decreased, on average, with age. Multi-level modelling indicated that authoritarian parenting (low warmth, high control) in Grade 7 predicted later (low) psychological flexibility. Moreover, increases in authoritarian parenting and decreases in authoritative parenting (high warmth and control) were associated with adolescent psychological flexibility across the high school years. Change in parenting predicted future psychological flexibility but did not predict change over time. Structural Equation Modelling revealed that adolescent psychological flexibility in Grade 9 predicted later decreases in authoritarian and increases in authoritative parenting. We discuss the implications of these findings for understanding how parenting changes and the consequences of such change for the development of psychological flexibility. PMID- 22311520 TI - Changes in physical activity in leisure time and the risk of myocardial infarction, ischemic heart disease, and all-cause mortality. AB - Physical activity is associated to a lower risk of mortality from all-causes and from coronary heart disease. The long-term effects of changes in physical activity on coronary heart disease are, however, less known. We examined the association between changes in leisure time physical activity and the risk of myocardial infarction (MI), ischemic heart disease (IHD), and all-cause mortality as well as changes in blood pressure in 4,487 men and 5,956 women in the Copenhagen City Heart Study. Physical activity was measured in 1976-1978 and 1981 1983 and participants were followed in nation-wide registers until 2009. Men who decreased physical activity by at least two levels and women who decreased by one level had a higher risk of MI relatively to an unchanged physical activity level (hazard ratio [HR] = 1.74, 95% confidence interval [95% CI]: 1.17-2.60 and HR = 1.30, 95% CI: 1.03-1.65). Similar associations were found for IHD although only significant in women. In all-cause mortality, men who increased physical activity had a lower risk and both men and women who reduced physical activity had a higher risk compared to an unchanged physical activity level. No association between changes in physical activity and blood pressure was observed. Findings from this prospective study suggest that changes in physical activity affect the risk of MI, IHD and all-cause mortality. A decrease in physical activity was associated to a higher risk of coronary heart disease. PMID- 22311522 TI - Words and reasons: psychiatry and assisted suicide. PMID- 22311523 TI - Physician-assisted suicide: saying what we mean and meaning what we say. PMID- 22311524 TI - What should we tell medical students and residents about euthanasia and assisted suicide? PMID- 22311525 TI - Palliative models of care for later stages of mental disorder: maximizing recovery, maintaining hope, and building morale. AB - BACKGROUND: The concept of staging of disease in psychiatry has developed over the past years. A neglected component of this model pertains to people in the advanced stages of a mental illness, who remain symptomatic and functionally impaired despite treatment. These patients are often high service utilizers, receiving complex multimodal treatments where the balance of risk and benefit shifts perceptibly. In this paper, we argue the need to adopt 'palliative' models of care for some individuals, and consider changing the therapeutic goals to follow care pathways similar to those used in other chronic and refractory medical illnesses. METHOD: Data was sourced by a literature search using Medline and a hand search of scientific journals. Relevant articles were selected. RESULTS: Clinical staging can help us better define subgroups of patients who will benefit from different goals and treatment. In the most advanced stage group, we find patients with persistent symptoms and treatment resistance. In these situations, it may be preferable to follow some of the principles of palliative care, which include the setting of attainable goals, reduction of side effects, limited symptom control, targeting identified psychological and social problems, and attempting to attain the best quality of life for these patients and their families. CONCLUSIONS: It is in the interest of those in the advanced phases of a disorder that clinicians acknowledge the limitations of treatment and actively attempt to plan treatment utilizing alternate models. It is essential to be clear that such approaches do not equate to the abandonment of care, but rather to the reconceptualizing of feasible and personalized treatment goals, a rebalancing of the risks and benefits of intervention, the management of illness behaviour, and the approaches that allow the patient to live gainfully within their limitations. PMID- 22311526 TI - Prediction of remission and recovery in young people presenting with first episode psychosis in Hong Kong: a 3-year follow-up study. AB - OBJECTIVE: The aim of the current study was to investigate the rates and predictors of symptomatic remission and recovery in patients presenting with first-episode psychosis 3 years after treatment initiation. METHODS: Seven hundred participants aged 15-25 years consecutively enrolled in a territory-wide early intervention programme in Hong Kong from July 2001 to August 2003 fulfilled study inclusion criteria, with 539 completing 3-year follow-up. Baseline and follow-up variables were collected via systematic medical file review. The operational criteria for recovery were based on clinical definition incorporating both symptom and functional dimensions. RESULTS: By the end of 3-year follow-up, 58.8% (n = 317) and 17.4% (n = 94) of participants met criteria for symptomatic remission and recovery, respectively. Around half (51.2%, n = 276) were not remitted either symptomatically or functionally in the last 12 months of follow up. Of those who achieved sustained symptomatic remission, only 43.1% were also in functional remission. Patients in symptomatic remission had lower rate of admissions, shorter duration of hospitalisations and more favourable psychosocial functioning than non-remitted counterparts. Logistic regression analysis revealed that female sex, older age of onset of psychosis, shorter duration of untreated psychosis (DUP) and early symptom resolution predicted symptomatic remission at the end of follow-up. Higher educational attainment, superior baseline occupational status and shorter DUP were found to be predictive of recovery. CONCLUSION: In a large representative cohort of Chinese young people presenting with first-episode psychosis, although more than half achieved symptomatic remission 3 years after service entry, the rates of functional remission and recovery were low. More intensive psychosocial interventions may be required to further improve patients' functional outcome. PMID- 22311527 TI - Social connectedness: a potential aetiological factor in the development of child post-traumatic stress disorder. AB - OBJECTIVE: The aim of this study was to investigate a new social connectedness factor and Posttraumatic Stress Disorder (PTSD) in children who experienced a cyclone disaster. METHOD: Three months post-disaster school-based screening for PTSD was conducted. 804 children (mean age = 10.22 years, SD = 1.24) participated. 12.0% of children reported severe or very severe PTSD symptoms. RESULTS: Low connected children, adjusted for age, gender and independent of cyclone exposure and threat perception, were 3.96 times more likely to experience severe to very severe PTSD. A structural model of child PTSD indicated that connectedness was the most important factor explaining variance in children's symptomatology. The final model accounted for 60% of the variance of child PTSD scores. CONCLUSIONS: We conclude that child connectedness is a new, significant, independent factor in a model of post-disaster child PTSD. Connectedness may represent a vulnerability factor that can be targeted preventatively in children in disaster-prone regions. Conversely, a pre-disaster intervention that helps children develop high connectedness may have the potential to confer resilience. PMID- 22311528 TI - The comorbidity between eating disorders and anxiety disorders: prevalence in an eating disorder sample and anxiety disorder sample. AB - OBJECTIVE: To investigate the prevalence of comorbid eating and anxiety disorders in women presenting for inpatient and outpatient treatment of an eating disorder and women presenting for outpatient treatment of an anxiety disorder. METHODS: The prevalence of comorbidity was investigated from a sample of 152 women, which included 100 women presenting for treatment of an eating disorder and 52 women presenting for treatment of an anxiety disorder. RESULTS: Of women presenting for treatment of an eating disorder, 65% also met criteria for at least one comorbid anxiety disorder; 69% of these reported the onset of the anxiety disorder to precede the onset of the eating disorder. Of the anxiety disorders diagnosed, social phobia was most frequently diagnosed (42%) followed by post-traumatic stress disorder (26%), generalised anxiety disorder (23%), obsessive-compulsive disorder (5%), panic/agoraphobia (3%) and specific phobia (2%). We also found that 13.5% of women presenting for anxiety treatment also met criteria for a comorbid eating disorder. Furthermore, 71% (n = 5) reported the onset of the anxiety disorder to precede the onset of the eating disorder. DISCUSSION: The results of this study suggest that the prevalence of eating and anxiety disorder comorbidity is high. The present research should improve the clinical understanding of the comorbidity between eating disorders and anxiety disorders. In particular, it is anticipated that this research will have significant aetiological and therapeutic implications especially with regard to improving the clinical effectiveness of psychological treatments for eating disorders and highlighting the importance of screening for eating pathology in the clinical assessment of anxiety disorders. PMID- 22311529 TI - Significant relationship between lifetime alcohol use disorders and suicide attempts in an Australian schizophrenia sample. AB - OBJECTIVE: Suicide and attempted suicide are common in individuals with schizophrenia, and evidence exists for a link between substance use disorders and suicidality in this disorder. However, alcohol has not been consistently implicated. We examined the relationship between substance use disorders and suicide attempts in schizophrenia. METHODS: We recruited a schizophrenia sample in Australia (n = 821) for genetic analyses. We analysed demographic and clinical variables, including substance use disorders, and their relationship to suicide attempts using generalised equation modelling. RESULTS: A significant association was identified between lifetime alcohol abuse/dependence and suicide attempts (OR = 1.66; 95% CI, 1.23 to 2.24; p = 0.001) after adjustment for potential confounders, but not between cannabis abuse/dependence and suicide attempts, nor between other illicit drug abuse/dependence and suicide attempts. Polysubstance abuse/dependence was also not implicated. CONCLUSIONS: These results suggest that the presence of alcohol abuse/dependence may be a risk factor for suicide attempts in individuals with schizophrenia, independent of comorbid substance abuse/dependence. PMID- 22311531 TI - Therapeutic effects of cerebrolysin added to risperidone in patients with schizophrenia dominated by negative symptoms. AB - OBJECTIVE: Cerebrolysin is a nootropic drug with unique neurotrophic activities directly affecting cerebral neurons. This study evaluated the efficacy and safety of cerebrolysin added to risperidone in patients with schizophrenia dominated by negative symptoms. METHODS: The trial was a double-blind, placebo-controlled, parallel-group design. A total of 109 patients who met the DSM-IV diagnostic criteria for schizophrenia were randomly assigned to cerebrolysin (cerebrolysin plus risperidone, n=55) or placebo (risperidone only, n=54) groups. Intravenous infusions of 30 ml cerebrolysin or placebo were given once daily from Monday to Friday for 4 weeks. Efficacy was assessed with measurements including the Positive and Negative Symptoms Scale (PANSS), Wechsler Memory Scale (WMS), modified Chinese Wechsler Adult Intelligence Scale (mWAIS). and Clinical Global Impression (CGI). RESULTS: Patients in both groups demonstrated improvements in psychiatric symptoms and cognitive and memory performance as assessed by PANSS, mWAIS, and WMS over the trial. There was no difference in rates of change in the PANSS total score or negative score between the two treatment groups. Patients treated with cerebrolysin showed significantly greater improvements in cognitive and memory function from week 2. No severe treatment adverse events were observed in either group. The frequency of adverse events was comparable between the two groups at the end of the treatment. CONCLUSION: Cerebrolysin added to risperidone did not augment the efficacy of risperidone in treating the psychotic symptoms of schizophrenia patients over an 8-week trial. Cerebrolysin at 30 ml per day as an adjunctive treatment was safe and may improve cognitive and memory functions of patients with schizophrenia dominated by negative symptoms. PMID- 22311530 TI - Visual memory in methamphetamine-dependent individuals: deficient strategic control of encoding and retrieval. AB - OBJECTIVE: Chronic use of methamphetamine (MA) has moderate effects on neurocognitive functions associated with frontal systems, including the executive aspects of verbal episodic memory. Extending this literature, the current study examined the effects of MA on visual episodic memory with the hypothesis that a profile of deficient strategic encoding and retrieval processes would be revealed for visuospatial information (i.e., simple geometric designs), including possible differential effects on source versus item recall. METHOD: The sample comprised 114 MA-dependent (MA+) and 110 demographically-matched MA-nondependent comparison participants (MA-) who completed the Brief Visuospatial Memory Test-Revised (BVMT R), which was scored for standard learning and memory indices, as well as novel item (i.e., figure) and source (i.e., location) memory indices. RESULTS: Results revealed a profile of impaired immediate and delayed free recall (p<0.05) in the context of preserved learning slope, retention, and recognition discriminability in the MA+ group. The MA+ group also performed more poorly than MA- participants on Item visual memory (p<0.05) but not Source visual memory (p>0.05), and no group by task-type interaction was observed (p>0.05). Item visual memory demonstrated significant associations with executive dysfunction, deficits in working memory, and shorter length of abstinence from MA use (p<0.05). CONCLUSIONS: These visual memory findings are commensurate with studies reporting deficient strategic verbal encoding and retrieval in MA users that are posited to reflect the vulnerability of frontostriatal circuits to the neurotoxic effects of MA. Potential clinical implications of these visual memory deficits are discussed. PMID- 22311532 TI - Clinical and neurocognitive profiles of subjects at high risk for psychosis with and without obsessive-compulsive symptoms. AB - OBJECTIVE: Obsessive-compulsive symptoms (OCS), which are common in psychotic spectrum illnesses, are of clinical interest because of their association with poor prognosis or cognitive dysfunction. However, few studies on the clinical and neurocognitive implications of OCS in individuals at ultra-high risk for psychosis (UHR) have been conducted. METHOD: Sixty-five UHR subjects [24 with OCS (UHR+OCS), 41 without OCS (UHR-OCS)], and 40 healthy controls were assessed using clinical scales and neurocognitive tests. RESULTS: Those with UHR+OCS showed more severe clinical symptoms and poorer global functioning as compared to both healthy controls and the UHR-OCS group, according to the results of the Global Assessment of Functioning, the Comprehensive Assessment of At-Risk Mental States, and the Positive and Negative Syndrome Scale (total, negative, and general scores). In the neurocognitive domain, those in the UHR-OCS group showed notably greater latency in the Stroop task and more confabulation errors in immediate recall in the Rey-Osterrieth Complex Figure Test compared with those in UHR+OCS group, whose performance levels were similar to those of the healthy control group. CONCLUSIONS: The OCS manifested in UHR individuals was associated with a more severe clinical symptomatic presentation, including lower global functioning and more psychotic symptoms. On the other hand, those with UHR-OCS performed more poorly on some cognitive tests. The features that distinguish the groups can be used for developing prognoses and intervention strategies for the heterogeneous UHR group. PMID- 22311533 TI - Palliative models of care for later stages of mental disorder: maximising recovery, maintaining hope and building morale. PMID- 22311534 TI - Problems with suicide risk assessment. PMID- 22311535 TI - Risk assessment for suicide and violence is of extremely limited value in general psychiatric practice. PMID- 22311536 TI - Delusion of paternity. PMID- 22311537 TI - A change from risperidone long acting injection to paliperidone palmitate in an elderly patient--a cautionary tale. PMID- 22311538 TI - Compulsive kissing: obsessive compulsive disorder with neurocognitive dysfunction. PMID- 22311539 TI - Transient citalopram-induced auditory hallucinations in a patient with Parkinson's disease and depression. PMID- 22311540 TI - Abstracts of the 2011 World Molecular Imaging Congress. San Diego, California, USA. September 7-10, 2011. PMID- 22311541 TI - A cone-shaped phantom for assessment of small animal PET scatter fraction and count rate performance. AB - PURPOSE: Positron emission tomography (PET) image quality deteriorates as the object size increases owing to increased detection of scattered and random events. The characterization of the scatter component in small animal PET imaging has received little attention owing to the small scatter fraction (SF) when imaging rodents. The purpose of this study is first to design and fabricate a cone-shaped phantom which can be used for measurement of object size-dependent SF and noise equivalent count rates (NECR), and second, to assess these parameters for two small animal PET scanners as function of radial offset, object size and lower energy threshold (LET). METHODS: The X-PETTM and LabPET-8TM scanners were modeled as realistically as possible using GATE Monte Carlo simulation platform. The simulation models were validated against experimental measurements in terms of sensitivity, SF and NECR. The dedicated phantom was fabricated in-house using high-density polyethylene. The optimized dimensions of the cone-shaped phantom are 158 mm (length), 20 mm (minimum diameter), 70 mm (maximum diameter) and taper angle of 9 degrees . RESULTS: The relative difference between simulated and experimental results for the LabPET-8TM scanner varied between 0.7% and 10% except for a few results where it was below 16%. Depending on the radial offset from the center of the central axial field-of-view (3-6 cm diameter), the SF for the cone-shaped phantom varied from 26.3% to 18.2%, 18.6 to 13.1% and 10.1 to 7.6% for the X-PETTM, whereas it varied from 34.4% to 26.9%, 19.1 to 17.0% and 9.1 to 7.3% for the LabPET-8TM, for LETs of 250, 350 and 425 keV, respectively. The SF increases as the radial offset decreases, LET decreases and object size increases. The SF is higher for the LabPET-8TM compared with the X-PETTM scanner. The NECR increases as the radial offset increases and object size decreases. The maximum NECR was obtained at a LET of 350 keV for the LabPET-8TM and 250 keV for the X-PETTM. High correlation coefficients for SF and NECR were observed between the cone-shaped phantom and an equivalent volume cylindrical phantom for the three considered axial fields of view. CONCLUSIONS: A single cone-shaped phantom enables the assessment of the impact of three factors, namely radial offset, LET and object size on PET SF and count rate estimates. This phantom is more realistic owing to the non-uniform shape of rodents' bodies compared to cylindrical uniform phantoms and seems to be well suited for evaluation of object size-dependent SF and NECR. PMID- 22311542 TI - Antiviral therapies for respiratory viral infections in lung transplant patients. AB - Because the lung is in constant contact with the environment, infections with respiratory viruses are a common and potentially serious complication of lung transplantation. Infection can cause direct effects, typically manifested as respiratory symptoms and changes in pulmonary function, and indirect effects, such as an enhanced risk of developing chronic allograft rejection. Infections with all of the identified respiratory viruses have been associated with infection in lung transplant recipients. Specific antiviral options have been studied for influenza and respiratory syncytial virus, and investigational agents are in development for other respiratory viruses. This paper will review the epidemiology and management strategies of respiratory viral infections in lung transplant recipients. PMID- 22311543 TI - Usefulness of perflubutane microbubble-enhanced ultrasound in imaging and detection of prostate cancer: phase II multicenter clinical trial. AB - PURPOSE: To explore the possibility of targeted biopsy (TBx) using transrectal ultrasound (US) with perflubutane microbubbles, we studied the findings of different cancerous tissue imaging modalities and evaluated needle biopsy in prostate cancer (PCa) using contrast-enhanced US (CEUS) in a multicenter clinical trial. METHODS: Seventy-one patients undergoing prostate biopsy received intravenous injection of perflubutane microbubbles (Sonazoid((r))). We evaluated and compared images obtained by CEUS. The safety observation period was 2 days after contrast administration. RESULTS: Among the 30 patients with cancer, one or more sites with findings suggestive of cancer in CEUS were detected in 23 patients (32.4%) by TBx. Although 22 patients had positive cores of cancer by systematic biopsy (SBx), 8 patients had positive cores of cancer in TBx alone (11.3%). There was a significant difference in cancer detection rate by TBx between two cohorts with PSA < 10 ng/mL (22.9%) and PSA >= 10 ng/mL (52.2%) (P < 0.02). Close observation of various CEUS findings with Sonazoid((r)) enabled targeting of cancerous areas, and consequently, a significant difference (P < 0.05) in the detection rate of cancer was recognized in the transition zone (TZ): SBx; 21/120 (17.5%) and TBx; 17/55 (30.9%). The incidence of adverse events was 6.7% and that of adverse reactions was 4%. CONCLUSIONS: CEUS with Sonazoid((r)) improved the detection rate of PCa by visualizing cancerous lesions. More detailed examination of CEUS images provided efficient characterization especially in the TZ area. TBx according to this procedure is expected to enable a lower number of biopsies and more accurate diagnosis of PCa. PMID- 22311544 TI - Shining worms in oysters: early scientific papers about luminescence. PMID- 22311545 TI - Detection of erythrocytes in patients with multiple myeloma using atomic force microscopy. AB - The goal of this study was to examine the pathophysiological changes to erythrocytes in multiple myeloma (MM) patients at a nanometer scale. We hypothesize that studying changes in red blood cells may be important for early diagnosis and effective treatment of MM. Blood samples were taken from ten healthy volunteers and ten MM patients before and after treatment. Changes in the morphological and biomechanical properties of the erythrocytes were studied at a nanometer scale with atomic force microscopy (AFM). There were dramatic deformations in the overall shape and surface membrane of the erythrocytes from pre- and post therapeutic MM patients compared with the healthy controls. Healthy and pathological MM erythrocytes could be distinguished by several morphologic parameters, including the width, length, length to width ratio, valley, peak, valley-to-peak, standard deviation, and surface fluctuation. The effectiveness of disease treatment could also be evaluated by studying these red blood cell parameters. AFM was able to detect noticeable morphological differences in the red blood cells from MM patients compared with healthy controls. Therefore, erythrocyte morphology is an important parameter for diagnosing MM, as well as evaluating the efficacy of disease treatment. PMID- 22311546 TI - Primitive neuroectodermal tumor of ovary in a young lady, confirmed with molecular and cytogenetic results--a rare case report with a diagnostic and therapeutic challenge. PMID- 22311547 TI - Evaluating the traditional Chinese literature for herbal formulae and individual herbs used for age-related dementia and memory impairment. AB - Natural products are the basis of many systems of traditional medicine and continue to provide sources for new drugs. Ethnobiological approaches to drug discovery that have proven productive in the past include the investigation of traditional medical literatures. This study describes a broadly applicable method for locating, selecting and evaluating citations in the traditional Chinese herbal medicine literature of the dynastic period (until 1911) for specific symptoms or disorders. This methodology is applied to evaluate multi-herb formulae for age-related dementia and memory impairment. Of the 174 multi-herb formulae located in the searches, 19 were for disorders broadly consistent with amnestic Mild Cognitive Impairment (MCI) and/or Age Associated Memory Impairment (AAMI). These appeared in books written between c. 650 to 1911. Of the 176 herbs that appeared in these 19 formulae, those with the highest frequencies were tabulated and hierarchical cluster analysis was undertaken. Chinese pharmacopoeias were consulted to determine the botanical identity of the herbs and also which herbs within the formulas were specific for memory disorders. This study found that the top ten herbs, in terms of frequency of inclusion in multi herb formulae specific for age-related memory disorders, were all listed in the pharmacopoeias for memory disorders and these formed three clusters. The herbs identified in this study may warrant further experimental and clinical evaluation both individually and in combination. PMID- 22311548 TI - Analysis of benthic invertebrate communities as a function of distance from two fish-processing plant effluent discharges in New Brunswick, Canada. AB - Benthic invertebrate communities have been known to change due to impacts from nutrient-rich industrial outputs, such as those from pulp and paper, sewage treatment plants, or aquaculture. Fish-processing plants have been recognized as contributors of large volumes of nutrient rich effluent to marine and estuarine environments, but their effect on benthic invertebrate communities is unknown. Benthic invertebrates and sediment samples were obtained from marine sampling stations at 0-, 10-, 30-, and 100-m distances from two fish-processing outfalls in Atlantic Canada. Sediment grain size, total organic carbon (TOC), ammonia, sulphide, and redox, as well as invertebrate abundance, density, taxa richness, Simpson's Inverse Diversity Index, Bray-Curtis Index of (%) Similarity, and the AZTI marine biotic index (AMBI), were determined for all sampling sites. Results from this study illustrate that taxa richness and density significantly increased as distance from the outfall discharge increased. In our study, TOC was only significantly correlated to AMBI but not to the other benthic invertebrate assemblage descriptors calculated in this study (invertebrate density, taxa richness, Simpson's Inverse Diversity Index). The study results suggest that taxa richness and density may be affected by effluent from fish-processing plants. PMID- 22311549 TI - Decabromobiphenyl, polybrominated diphenyl ethers, and brominated phenolic compounds in serum of cats diagnosed with the endocrine disease feline hyperthyroidism. AB - The incidence of cats being diagnosed with feline hyperthyroidism (FH) has increased greatly since it was first described in 1979. The cause of FH has not been established. Hypothetically, there is a link between increasing FH and exposure to brominated flame retardants. Much greater polybrominated diphenyl ethers (PBDE) concentrations have been reported in cat serum compared with human serum, likely due to cat licking behaviour. This study aimed to extend the present identification of brominated compounds in cat serum, with a focus on hydroxylated metabolites of PBDE, to improve the understanding of feline metabolism of PBDEs. A pooled serum sample from 30 Swedish pet cats with FH was analysed, and brominated species were identified. The results showed exposure to the discontinued flame retardant decabromobiphenyl (BB-209) and technical penta- and octa-BDEs. Altogether 12 PBDE congeners were identified along with 2'-MeO BDE68. Furthermore, 2,4-dibromophenol, 2,4,6-, 2,4,5- and 2,3,4-tribromophenol plus 2'-OH-BDE68, 6-OH-BDE47, 5-OH-BDE47, 4'-OH-BDE49 were identified. 2,4,6 tribromophenol and 6-OH-BDE47 were the most prominent species in cat serum. Considering that these are natural products, it can be concluded that metabolism of PBDEs to OH-PBDEs is not a major route of PBDE elimination in cats. It is notable that BB-209, 6-OH-BDE47, and 2,4,6-tribromophenol all suggested that endocrine-disrupting chemicals were present in high concentrations in cat serum. PMID- 22311550 TI - Effect of chemical structure and network formation on physical properties of di(cyanate ester) thermosets. AB - Key physical properties of three dicyanate ester monomers, bisphenol A dicyanate (BADCy), bisphenol E dicyanate (LECy), and the dicyanate of a silicon-containing analogue of bisphenol A (SiMCy) were investigated as a function of cyanurate conversion at conversions ranging from approximately 70% to greater than 90% in order to assess the range of applicability of both traditional and more unusual structure-property-process relationships known for cyanate ester resins. A more complete understanding of these relationships is essential for the continued development of cyanate ester resins and their composites for a wide variety of aerospace applications. The degree of cure in each system was determined by differential scanning calorimetry (DSC). The degree of conversion achieved at a given temperature was dependent on the structure of the repeat unit, with SiMCy displaying the highest relative ease of cure. The density at room temperature was found to decrease monotonically with increasing conversion for all monomer types studied. In contrast, the water uptake decreased with increasing cure for all three materials over most or all of the conversion range studied, but leveled off or began to increase with increasing conversion at conversions of approximately 90%. The T(g) decreased after exposure to hot water in resins with greater than 85% conversion, but unexpectedly increased in samples with lower conversions. An investigation of the effect of hot water exposure on network chemistry via infrared spectroscopy indicated that carbamate formation varied with both monomer chemistry and extent of cure, but was greatest for the BADCy polycyanurates. On the other hand, the unreacted cyanate ester band tended to disappear uniformly, suggesting that reactions other than carbamate formation (such as cyclotrimerization) may also take place during exposure to hot water, possibly giving rise to the observed unusual increases in T(g) upon exposure. PMID- 22311551 TI - Osteophilic multilayer coatings for accelerated bone tissue growth. AB - Osteophilic modular nanostructured multilayers containing hydroxyapatite nanoparticles complexed with a natural polymer chitosan create an osteoconductive surface for mesenchymal stem cells (MSCs). Coupled with the sustained release of physiological amounts of osteoinductive bone morphogenetic protein over several days from degradable poly(beta-amino ester) based multilayers, this single coating results in a synergistic accelerated and upregulated differentiation of MSCs into osteoblasts laying down new bone tissue on orthopedic implants. PMID- 22311552 TI - Heart rate recovery in obstructive sleep apnea: obesity or not? PMID- 22311553 TI - Insomnia symptoms influence CPAP compliance. AB - PURPOSE: The aim of this study is to determine parameters which influence 6-month compliance of continuous positive airway pressure therapy (CPAP) in patients with obstructive sleep apnea syndrome (OSAS). METHODS: This prospective study investigated 73 patients (24 females) with OSAS and medical indication for CPAP therapy: age 55.1 +/- 11.5 years, body mass index (BMI) 30.8 +/- 5.0 kg/m2, Apnea Hypopnea Index (AHI) 39.2 +/- 26.7/h, Oxygen Desaturation Index (ODI) 33.2 +/- 25.4/h, minimum O(2) saturation 78.9 +/- 7.6%. The influence of baseline parameters (demographic and polysomnographic data, sleeping medication intakes, BMI, psychometrics [Epworth Sleepiness Scale, Regensburg Insomnia Scale, Vigilance test and Beck Depression Inventory]) on 6-month compliance was evaluated with a correlation and a linear regression analysis. RESULTS: The baseline value of the Regensburg Insomnia Scale (RIS) predicts 6-month CPAP compliance (r = -0.376, R (2) = 0.14, p < 0.001), although no other baseline parameter correlates. Patients with a compliance of <4 h/night show higher RIS scores, i.e., more insomnia symptoms (17.6 +/- 8.8) compared to those with >=4 h/night (12.6 +/- 6.9; p < 0.05). CONCLUSIONS: Insomnia symptoms prior to the beginning of CPAP treatment show a negative influence on CPAP compliance. Further studies should clarify, if a treatment of insomnia symptoms leads to a benefit in compliance. PMID- 22311554 TI - The effects of heated humidifier in continuous positive airway pressure titration. AB - BACKGROUND: Previous studies have shown that routine heated humidifier (HH) do not provide any benefit during continuous positive airway pressure (CPAP) titration if there are no significant naso-pharyngeal symptoms. In clinical practice, nasal diseases and upper airway symptoms are very common. This study investigates the effects of HH during CPAP titration in subjects with or without naso-pharyngeal symptoms. METHODS: Fifty-two patients who received polysomnography with CPAP titration were randomly assigned to HH and non-HH groups. Their nasal cavity, pharynx, and naso-pharynx were evaluated before CPAP titration, and a questionnaire on subjective sensation, including naso-pharyngeal symptoms, willingness to further use CPAP, and sleep improvement, was used. Objective (e.g., leak, apnea-hypopnea index (AHI) reduction, and optimal CPAP pressure level) and subjective data were analyzed between the two groups. RESULTS: In subjective sensation, the HH group did not have any benefit in further willingness to use CPAP and in sleep improvement, but had improved naso pharyngeal symptoms (p = 0.043). There were no significant differences in leak, AHI reduction, and optimal CPAP pressure, even in patients with significant naso pharyngeal symptoms. CONCLUSION: Routine use of HH is not necessary during CPAP titration regardless of naso-pharyngeal symptoms. PMID- 22311555 TI - Cutaneous T-cell lymphomas: a review of new discoveries and treatments. AB - Treatment regimens of patients with CTCL vary widely based on clinician preference and patient tolerance. Skin directed therapies are recommended for patients with early stage IA and IB MF, with combinations used in refractory cases. While no regimen has been proven to prolong survival in advanced stages, immunomodulatory regimens should be used initially to reduce the need for cytotoxic therapies. In more advanced stages of disease, treatment efforts should strive for palliation and improvement of quality of life. With many new therapies and strategies on the horizon, the future looks promising for CTCL patients. Unfortunately, other than allogeneic HCT, there are no potential curative therapies for CTCL. Clinical trials are currently underway to identify new therapies to improve quality of life for patients, and researchers are hard at work to identify novel pathways and genes for prognostication and as targets for therapies. Importantly, collaborative clinical trials to enhance rates of accrual need to be conducted, and improved interpretation of data via standardizing end points and response criteria should be an emphasis. Recently, the International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous Lymphoma Consortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer (EORTC) met to develop consensus guidelines to facilitate collaboration on clinical trials. These proposed guidelines consist of: recommendations for standardizing general protocol design; a scoring system for assessing tumor burden in skin, lymph nodes, blood, and viscera; definition of response in skin, nodes, blood, and viscera; a composite global response score; and a definition of end points. Although these guidelines were generated by consensus panels, they have not been prospectively or retrospectively validated through analysis of large patient cohorts. PMID- 22311556 TI - Effects of castration on aggression and levels of serum sex hormones and their central receptors in mandarin voles (Microtus mandarinus). AB - Aggression in socially monogamous mandarin vole (Microtus mandarinus) was observed after castration. Levels of serum sex hormones and their central receptors were also measured using enzyme-linked immunosorbent assay and immunohistochemistry methods. The data indicate that adult males showed higher levels of aggression after castration. However, castration significantly reduced levels of serum testosterone, and the number of androgen receptor immunoreactive neurons in the anterior hypothalamus, bed nucleus of the stria terminalis, medial amygdaloid nucleus (P<0.01) and lateral septal nucleus (P<0.05). In addition, levels of estrogen receptor beta in the anterior hypothalamus and medial amygdaloid nucleus (P<0.05), bed nucleus of the stria terminalis and lateral septal nucleus (P<0.01) declined to varying degrees at weekly intervals. In contrast, serum 17beta-estradiol concentrations were up-regulated by castration and castration did not change levels of estrogen receptor alpha in the medial amygdaloid nucleus and lateral septal nucleus, but increased it in the anterior hypothalamus 3 weeks after castration (P<0.05). We suggest that higher levels of aggression induced by castration may be independent of serum testosterone and androgen receptors, and may be associated with high serum 17beta-estradiol concentrations, stable estrogen receptor alpha immunoreactive neurons in some brain regions and the relative ratio of the two estrogen receptors. PMID- 22311557 TI - Discrimination of inclined path segments by the desert ant Cataglyphis fortis. AB - Desert ants (Cataglyphis fortis) navigate by means of path integration, and perform accurately even in undulating terrain. They are able to correctly calculate the ground distance between nest and feeder even if their foraging excursion leads them over corrugated surfaces. To compute the respective ground projection when walking over an inclined surface, ants must measure its slope with sufficient accuracy--but how they do so is still not understood. Using a new behavioural assay that included a negative reinforcement, we investigated how well different slopes are discriminated by the ants. Ants were trained to visit an elevated feeder, via a ramp of fixed inclination (five training inclinations were used: 0 degrees , 15 degrees , 30 degrees , 45 degrees , 60 degrees ). The ants discriminated a steeper test slope that differed from the training slope by 12.5 degrees . This discrimination performance was found to be constant for training slopes between 0 degrees and 45 degrees . Ants trained on a 60 degrees slope, however, did not discriminate all steeper slopes, up to a vertical ascent, from the 60 degrees inclination. The consequences of this discrimination accuracy for errors in the path integration process are discussed. PMID- 22311558 TI - Structure and dynamics of the actin-based smooth muscle contractile and cytoskeletal apparatus. AB - The thin filaments of differentiated smooth muscle cells are composed of actin and tropomyosin isoforms and numerous ancillary actin-binding proteins that assemble together into distinct thin filament classes. These different filament classes are segregated in smooth muscle cells into structurally and functionally separated contractile and cytoskeletal cellular domains. Typically, thin filaments in smooth muscle cells have been considered to be relatively stable structures like those in striated cells. However, recent efforts have shown that smooth muscle thin filaments indeed are dynamic and that remodeling of the actin cytoskeleton, in particular, regulates smooth muscle function. Thus, the cytoskeleton of differentiated smooth muscle cells appears to function midway between that of less dynamic striated muscle cells and that of very plastic proliferative cells such as fibroblasts. Michael and Kate Barany keenly followed and participated in some of these studies, consistent with their broad interest in actin function and smooth muscle mechanisms. As a way of honoring the memory of these two pioneer members of the muscle research community, we review data on distribution and remodeling of thin filaments in smooth muscle cells, one of the many research topics that intrigued them. PMID- 22311559 TI - Comparison of stochastic and deterministic methods for mapping groundwater level spatial variability in sparsely monitored basins. AB - In sparsely monitored basins, accurate mapping of the spatial variability of groundwater level requires the interpolation of scattered data. This paper presents a comparison of deterministic interpolation methods, i.e. inverse distance weight (IDW) and minimum curvature (MC), with stochastic methods, i.e. ordinary kriging (OK), universal kriging (UK) and kriging with Delaunay triangulation (DK). The study area is the Mires Basin of Mesara Valley in Crete (Greece). This sparsely sampled basin has limited groundwater resources which are vital for the island's economy; spatial variations of the groundwater level are important for developing management and monitoring strategies. We evaluate the performance of the interpolation methods with respect to different statistical measures. The Spartan variogram family is applied for the first time to hydrological data and is shown to be optimal with respect to stochastic interpolation of this dataset. The three stochastic methods (OK, DK and UK) perform overall better than the deterministic counterparts (IDW and MC). DK, which is herein for the first time applied to hydrological data, yields the most accurate cross-validation estimate for the lowest value in the dataset. OK and UK lead to smooth isolevel contours, whilst DK and IDW generate more edges. The stochastic methods deliver estimates of prediction uncertainty which becomes highest near the southeastern border of the basin. PMID- 22311560 TI - Assessing heavy metal pollution in the water level fluctuation zone of China's Three Gorges Reservoir using geochemical and soil microbial approaches. AB - The water level fluctuation zone (WLFZ) in the Three Gorges Reservoir is located in the intersection of terrestrial and aquatic ecosystems, and assessing heavy metal pollution in the drown zone is critical for ecological remediation and water conservation. In this study, soils were collected in June and September 2009 in natural recovery area and revegetation area of the WLFZ, and geochemical approaches including geoaccumulation index (I (geo)) and factor analysis and soil microbial community structure were applied to assess the spatial variability and evaluate the influence of revegetation on metals in the WLFZ. Geochemical approaches demonstrated the moderate pollutant of Cd, the slight pollutant of Hg, and four types of pollutant sources including industrial and domestic wastewater, natural rock weathering, traffic exhaust, and crustal materials in the WLFZ. Our results also demonstrated significantly lower concentrations for elements of As, Cd, Pb, Zn, and Mn in the revegetation area. Moreover, soil microbial community structure failed to monitor the heavy metal pollution in such a relatively clean area. Our results suggest that revegetation plays an important role in controlling heavy metal pollution in the WLFZ of the Three Gorges Reservoir, China. PMID- 22311561 TI - Diagnosis, management and outcomes of adults hospitalized with influenza. AB - Annual influenza epidemics and periodic pandemics result in excess hospital admissions. Hospitalization typically occurs in those with underlying medical conditions, those at the extremes of age and in pregnant woman; young adults and obese individuals were also at increased risk during the 2009 H1N1 pandemic. Severe influenza pneumonia, exacerbation of underlying lung diseases, cardiovascular and cerebrovascular events and bacterial superinfection are common reasons for hospitalization. Clinical diagnosis is unreliable and virological confirmation can be challenging. Overall mortality among adults hospitalized with influenza ranges from 4% to 8%, although higher mortality (>10-15%) may be seen during pandemics and among the immunocompromised. Recent data have suggested that neuraminidase inhibitors, particularly when given early, can accelerate viral clearance and improve clinical outcomes in hospitalized adults; thus, antiviral treatment should be considered in all cases. Controlled clinical trials are urgently needed in this population to evaluate comparative treatment efficacy of different agents and combinations, including emergence of antiviral resistance, and to address issues related to dosage, duration and parenteral route. PMID- 22311562 TI - Transcriptome, proteome, and metabolome in dyssynchronous heart failure and CRT. AB - Cardiac resynchronization therapy reduces morbidity and mortality in patients with symptomatic systolic heart failure (New York Heart Association class III or IV) and ventricular conduction delay. The current review focuses on how high throughput technologies including gene expression profiling and proteomics have helped in our understanding of the pathophysiology of electromechanical dyssynchrony and the molecular mechanisms by which cardiac resynchronization therapy (CRT) exerts its beneficial effects. Comparing gene expression changes in early-activated anterior vs. late-activated lateral left ventricular myocardium in a large animal model of dyssynchronous heart failure, we demonstrated a profound effect of electromechanical dyssynchrony on the regional cardiac transcriptome, as changes in gene expression were primarily observed in the early activated anterior left ventricular myocardium. This increase in regional heterogeneity of gene expression within the left ventricle was reversed by CRT. Specifically, CRT remodeled transcripts with metabolic and cell signaling function, which was corroborated by protein data. In addition, high-throughput or "omic" techniques also hold great promise to identify key pathways and biomarkers that are regulated differentially in CRT responders vs. nonresponders. PMID- 22311563 TI - Electrical and mechanical ventricular activation during left bundle branch block and resynchronization. AB - Cardiac resynchronization therapy (CRT) aims to treat selected heart failure patients suffering from conduction abnormalities with left bundle branch block (LBBB) as the culprit disease. LBBB remained largely underinvestigated until it became apparent that the amount of response to CRT was heterogeneous and that the therapy and underlying pathology were thus incompletely understood. In this review, current knowledge concerning activation in LBBB and during biventricular pacing will be explored and applied to current CRT practice, highlighting novel ways to better measure and treat the electrical substrate. PMID- 22311564 TI - Combining time-resolved fluorescence with synchronous fluorescence spectroscopy to study bovine serum albumin-curcumin complex during unfolding and refolding processes. AB - We investigated the complex interaction between bovine serum albumin (BSA) and curcumin by combining time-resolved fluorescence and synchronous fluorescence spectroscopy. The interaction was significant and sensitive to fluorescence lifetime and synchronous fluorescence characteristics. Binding of curcumin significantly shortened the fluorescence lifetime of BSA with a bi-molecular quenching rate constant of k(q) = 3.17 * 10(12) M(-1) s(-1). Denaturation by urea unfolded the protein molecule by quenching the fluorescence lifetime of BSA. The tyrosine synchronous fluorescence spectra were blue shifted whereas the position of tryptophan synchronous fluorescence spectra was red shifted during the unfolding process. However, denaturation of urea had little effect on the synchronous fluorescence peak of tyrosine in curcumin-BSA complex except in the low concentration range; however, it shifted the peak to the red, indicating that curcumin shifted tryptophan moiety to a more polar environment in the unfolded state. Decreases in the time-resolved fluorescence lifetime and curcumin-BSA complex during unfolding were recovered during refolding of BSA by a dilution process, suggesting partial reversibility of the unfolding process for both BSA and curcumin-BSA complex. PMID- 22311565 TI - Sequence polymorphism characteristics in the See2beta gene from maize key inbred lines and derived lines in China. AB - Research on the sequence polymorphism characteristics of key genes is important in the early identification of maize inbred lines. The See2beta gene functions in remobilizing leaf nitrogen and exporting it to developing grain during foliar senescence. We analyzed See2beta sequences from 49 inbred lines representing four key lines and their derivatives: Huangzaosi, Mo17, Dan340, and Ye478. We found that the See2beta gene had one insertion and two deletions in most Huangzaosi lines and three insertions in the Mo17 group; that the Huangzaosi, Dan340, and Ye478 lines, but not the Mo17 line, had unique indels; and that the See2beta gene in lines derived from the same key inbred line had higher sequence homology, according to phenetic analysis of the inbred lines derived from Huangzaosi and Mo17. Thus, a candidate inbred line could be preliminarily identified using markers closely linked to the See2beta gene combined with sequence alignment of See2beta. PMID- 22311567 TI - Congenital long-QT syndrome in Addison's disease: a novel association. AB - This report describes a teenager found to have both Addision's disease and long QT syndrome type 1. This association is unique, but congenital long-QT channelopathies have been associated with other endocrinopathies. It remains to be seen whether genetic investigation should be performed for all patients with long-QTc's and endocrinopathies. PMID- 22311568 TI - Giant pulmonary valve cyst in a 7-year-old child. AB - This report describes the diagnosis and surgical management of a pulmonary valve cystic mass in a symptomatic 7-year-old boy. Cardiac valve cysts are extremely rare beyond the age of 6 months and typically not associated with symptoms. These lesions may grow, leading to progressive stenosis, regurgitation, or ventricular outflow tract obstruction. Therefore, these lesions should be monitored for change in size and/or, hemodynamic changes. Surgical intervention may be required for symptomatic patients. PMID- 22311569 TI - A contemporary assessment of the risk for sudden cardiac death in patients with congenital heart disease. AB - Assessment of the risk for sudden cardiac death (SCD) after surgery for congenital heart disease (CHD) remains a difficult challenge. In the study of this problem, the focus has evolved from concern regarding late-onset heart block to a subsequent focus on ventricular and reentrant atrial arrhythmias, with the most recent emphasis on ventricular dysfunction and heart failure. Sudden cardiac death in CHD patients has been studied most extensively in tetralogy of Fallot. More than 30 risk factors have been proposed, with age at repair, QRS duration, right ventricular enlargement, and left ventricular dysfunction considered the most predictive risk factors. Additionally, SCD has been studied in patients with atrial repair for transposition of the great arteries, left heart obstructive lesions, and to a limited extent, patients with univentricular physiology. This review discusses current risk factors for SCD in CHD and the limited positive predictive value of any individual factor. The emphasis is on contemporary patients with CHD, who differ markedly from those who had repair of CHD decades earlier. This is characterized by complete repairs during the neonatal period, improved physiologic outcomes, and extended survival of patients with complex forms of CHD. Therefore, earlier data and conclusions may not be relevant to newer generations of patients with CHD. According to current perspectives, systemic ventricular dysfunction becomes a major risk factor beyond the age of 20 years. The first symptomatic arrhythmia may result in SCD, and defibrillators are increasingly implanted despite the lack of risk stratification criteria. The large number of potential risk factors and therapeutic options, in contrast to the low incidence of actual events, results in a difficult clinical challenge in the assessment of the risk for SCD in the individual patient with CHD. PMID- 22311570 TI - Outcome of left atrial isomerism at a single institution. AB - Left atrial isomerism includes a complex spectrum of cardiac and extracardiac anomalies. The records of all patients with left isomerism born during the period of 1973-2010 and treated at the Children's Hospital, Helsinki were reviewed. The short- and long-term outcomes were studied. The review included 38 patients (50% females). The overall survival with left atrial isomerism was 63% during a median follow-up time of 16 years (range, 4-30 years). Extracardiac anomalies were noted in 14 (37%) of 38 cases. Cardiac defects included dextrocardia in 26%, partially or totally anomalous pulmonary venous return in 29%, common atrium in 50%, atrioventriculoseptal defect in 73%, single ventricle in 40%, ventriculoseptal defect without atrioventricular defect in 11%, transposition in 21%, double outlet of the right ventricle in 26%, pulmonary stenosis or atresia in 61%, and left ventricular outflow obstruction in 24% of the cases. Cardiac arrhythmias were presented in 71% and pacemaker treatment in 29% of the cases. Of the 38 patients, 33 had cardiac surgery. Simple palliative methods were used in 11 cases, single-ventricle palliation in 12 cases, and operation with a biventricular track in 10 cases. In the groups that had surgery, 3 of 11 patients, 3 of 12 patients, and 3 of 10 patients died, respectively. In this review, 14 deaths occurred, associated with extracardiac anomalies in five cases and with cardiac arrhythmia in four cases. Five postoperative deaths occurred. At this writing, all three patients who had heart transplantation are alive. Complicated heart defects associated with severe arrhythmias and extracardiac anomalies contribute to a high mortality rate with left isomerism. Cardiac transplantation was considered a good option for selected patients. PMID- 22311572 TI - Bronchial cast. PMID- 22311571 TI - Percutaneous coronary intervention for acute myocardial infarction in a pediatric patient with coronary aneurysm and stenosis due to Kawasaki disease. AB - We report the case of an acutely ill 3-year-old female, with a previous medical history of Kawasaki disease, who presented to care with an acute myocardial infarction. We describe the coordinated therapies employed by pediatric and adult cardiologists aimed to establish coronary revascularization. PMID- 22311573 TI - Determination of enantiomeric excess by chiral liquid chromatography without enantiomerically pure starting standards. AB - A facile approach for the enantiomeric excess determination of enantiomeric mixtures without the necessity of pure enantiomer standards is presented. Promethazine and trimeprazine commercial nonracemic mixtures were used as cases study to probe the validity of the method. Chromatographic resolutions obtained with a chiral column AGP in reverse phase mode were 1.32-1.16 (promethazine) and 1.20-0.93 (trimeprazine) for the three detectors (circular dichroism, photometric and fluorimetric) in series. Results obtained showed that enantiomeric excess was 10.4, 8.71 and 8.58% for promethazine and 1.60, 1.23 and 1.80% for trimeprazine (medium values of 9.23 +/- 1.01% and 1.54 +/- 0.29%, respectively). Recovery assay over human serum samples, at three concentration levels, spiked with prometazine and submitted to solid-phase extraction, gave values of 99.09-93.48% [S-(-) enantiomer] and 98.51-91.89% [R-(+)-enantiomer]. Detection limits of promethazine enantiomers were between 0.02 ug (fluorimetric) and 1 ug (circular dichroism), and 0.02-1.1 ug for trimeprazine. PMID- 22311574 TI - TiO(2) nanocages: fast synthesis, interior functionalization and improved lithium storage properties. PMID- 22311575 TI - Role of innate immunity in the pathogenesis of chronic rhinosinusitis: progress and new avenues. AB - Chronic rhinosinusitis is a heterogeneous and multifactorial disease with unknown etiology. Aberrant responses to microorganisms have been suggested to play a role in the pathophysiology of the disease. Research has focused on the presence, detection, response to, and eradication of these potential threats. Main topics seem to center on the contribution of structural cells such as epithelium and fibroblasts, on the consequences of activation of pattern-recognition receptors, and on the role of antimicrobial agents. This research should be viewed not only in the light of a comparison between healthy and diseased individuals, but also in a comparison between patients who do or do not respond to treatment. New players that could play a role in the pathophysiology seem to surface at regular intervals, adding to our understanding (and the complexity) of the disease and opening new avenues that may help fight this incapacitating disease. PMID- 22311576 TI - Factors influencing the quality of total mesorectal excision. AB - BACKGROUND: Total mesorectal excision (TME) has become the standard of care for rectal cancer. Incomplete TME may lead to local recurrence. METHODS: Data from the multicentre observational German Quality Assurance in Rectal Cancer Trial were used. Patients undergoing low anterior resection for rectal cancer between 1 January 2005 and 31 December 2009 were included. Multivariable analysis using a stepwise logistic regression model was performed to identify predictors of suboptimal TME. RESULTS: From a total of 6179 patients, complete data sets for 4606 patients were available for analysis. Pathological tumour category higher than T2 (pT3 versus pT1/2: odds ratio (OR) 1.22, 95 per cent confidence interval 1.01 to 1.47), tumour distance from the anal verge less than 8 cm (OR 1.27, 1.05 to 1.53), advanced age (65-80 years: OR 1.25, 1.03 to 1.52; over 80 years: OR 1.60, 1.15 to 2.22), presence of intraoperative complications (OR 1.63, 1.15 to 2.30), monopolar dissection technique (OR 1.43, 1.14 to 1.79) and low case volume (fewer than 20 procedures per year) of the operating surgeon (OR 1.20, 1.06 to 1.36) were independently associated with moderate or poor TME quality. CONCLUSION: TME quality was influenced by patient- and treatment-related factors. PMID- 22311577 TI - Environments for Healthy Living (EFHL) Griffith birth cohort study: background and methods. AB - The health of an individual is determined by the interaction of genetic and individual factors with wider social and environmental elements. Public health approaches to improving the health of disadvantaged populations will be most effective if they optimise influences at each of these levels, particularly in the early part of the life course. In order to better ascertain the relative contribution of these multi-level determinants there is a need for robust studies, longitudinal and prospective in nature, that examine individual, familial, social and environmental exposures. This paper describes the study background and methods, as it has been implemented in an Australian birth cohort study, Environments for Healthy Living (EFHL): The Griffith Study of Population Health. EFHL is a prospective, multi-level, multi-year longitudinal birth cohort study, designed to collect information from before birth through to adulthood across a spectrum of eco-epidemiological factors, including genetic material from cord-blood samples at birth, individual and familial factors, to spatial data on the living environment. EFHL commenced the pilot phase of recruitment in 2006 and open recruitment in 2007, with a target sample size of 4000 mother/infant dyads. Detailed information on each participant is obtained at birth, 12-months, 3 years, 5-years and subsequent three to five yearly intervals. The findings of this research will provide detailed evidence on the relative contribution of multi-level determinants of health, which can be used to inform social policy and intervention strategies that will facilitate healthy behaviours and choices across sub-populations. PMID- 22311578 TI - The relationship of socioeconomic status to preterm contractions and preterm delivery. AB - Spontaneous preterm labor precedes approximately 50% of preterm births. One to 10% of pregnant women are hospitalized for preterm labor. This study examines the relationship of socioeconomic indicators, family income, education and type of insurance, with preterm contractions and subsequent preterm delivery. Data were from the pregnancy risk assessment monitoring system on 107,926 women who had singleton births during 2000-2002. Data on preterm contractions, family income, and type of insurance during pregnancy were from the maternal questionnaire. Maternal education and gestational age were derived from birth certificate data. Predicted marginal probabilities from logistic regression models were used to calculate the adjusted cumulative incidence and cumulative risk ratio of preterm contractions and preterm delivery. Median annual household income was approximately $30,000. More than one-fourth (28.1 95% CI: 27.7, 28.6) of women experienced preterm contractions, and these women were 3 times as likely (18 vs. 5%) to deliver preterm as women without preterm contractions. Only 58% of women who delivered preterm reported contractions. Lower income and Medicaid-paid care were independently associated with an increased risk of preterm contractions but not with preterm delivery. The association of lower income and Medicaid enrollment with preterm contractions but not preterm delivery suggests that SES is associated with the initiation of the pathway to spontaneous preterm delivery rather than access to or the success of interventions to prevent delivery following the onset of contractions. PMID- 22311579 TI - Dental cleaning before and during pregnancy among Maryland mothers. AB - Despite increasing recognition of the importance of oral health to overall health, dental care utilization remains low in the US. Given the established link between maternal oral health and child oral health, this study examined factors related to preventive dental care utilization at two critical time points, before and during pregnancy. Data were obtained from a sample of 6,171 women who delivered a live birth during 2004-2008 and completed the Maryland Pregnancy Risk Assessment Monitoring System postpartum survey. Multinomial logistic analyses examined associations between predisposing and enabling factors with dental cleaning before and during pregnancy. Women with less than a high school education or a history of physical abuse and non-Hispanic black and Hispanic women were less likely to report teeth cleaning before and during pregnancy. Having no insurance at the start of pregnancy was associated with significantly lower risk of teeth cleaning before pregnancy and both before and during pregnancy. Receipt of oral health counseling during pregnancy was positively related to teeth cleaning during pregnancy. Dental cleaning is associated with insurance, oral health counseling and maternal factors such as race, ethnicity, education and history of physical abuse. Better integration of oral health into prenatal health care, particularly among ethnic and racial minority groups, may be beneficial to maternal and infant well-being. Oral health promotion, disease prevention and health care should be a part of the local, state and national health policy agendas. PMID- 22311580 TI - Detection of antibacterial-like activity on a silica surface: fluoroquinolones and their environmental metabolites. AB - BACKGROUND, SCOPE, AND AIMS: Antibacterial fluoroquinolones (FQs) are third generation antibiotics that are commonly used as therapeutic treatments of respiratory and urinary tract infections. They are used far less in intensively farmed animal production systems, though their use may be permitted in the veterinary treatments of flocks or in medicated feeds. When used, only a fraction of ingested parent FQ actually reaches the in vivo target site of infection, while the remainder is excreted as the parent FQ and its metabolized products. In many species' metabolism, enrofloxacin (EF) is converted into ciprofloxacin (CF) while both FQs are classified as parent FQs in human treatments. It is therefore likely that both FQs and their metabolic products will contribute to a common pool of metabolites in biological wastes. Wastes from intensive farming practices are either directly applied to agricultural land without treatment or may be temporarily stored prior to disposal. However, human waste is treated in sewage treatment plants (STPs) where it is converted into biosolids. In the storage or treatment process of STPs, FQs and their in vivo metabolites are further converted into other environmental metabolites (FQEMs) by ex vivo physicochemical processes that act and interact to produce complex mixtures of FQEMs, some of which have antibacterial-like activities. Biosolids are then often applied to agricultural land as a fertilizer amendment where FQs and FQEMs can be further converted into additional FQEMs by soil processes. It is therefore likely that FQ contaminated biowaste-treated soils will contain complex mixtures of FQEMs, some of which may have antibacterial-like activities that may be expressed on bacteria endemic to the receiving agricultural soil environment. Concern has arisen in the scientific and in the general community that repeated use of FQ-contaminated biowaste as fertilizer amendments of nutrient-impoverished agricultural land may create a selective environment in which FQ-resistant bacteria might grow. The likelihood of this happening will depend, to some extent, on whether bioactive FQEMs are first synthesized from the parent FQs by the action and interaction of in vivo and ex vivo processes producing bioactive FQEMs in biowastes and biosolids. The postulated creation of a selective environment will also depend, in part, on whether such bioactive FQEMs are biologically available to bacteria, which may, in turn, be influenced by soil type, amendment regime, and the persistence of the bioactive FQEMs. Additionally, soil bacteria and soil processes may be affected in different ways or extents by bioactive FQEMs that could possibly act additively or synergistically at ecological targets in these non-target bacteria. This is an important consideration, since, while parent FQs have well-defined ecological targets (DNA gyrase and topoisomerase IV) and modes of bactericidal action, the FQEMs and their possible modes of action on the many different species of soil bacteria is less well studied. It is therefore understandable that there is a lack of conclusive evidence directly attributing biosolid usage to any increase in FQ-resistant bacteria detected in biowaste amended agricultural soil. However, a lack of evidence may simply imply that a causal relationship between biosolid usage programs and any detection of low levels of FQ-resistant bacteria in soils has yet to be established, rather than an assumption of no relationship whatsoever. Based on results presented in this paper, the precautionary principle should be applied in the usage of FQ contaminated biosolids as fertilizer amendments of agricultural land. The aim of this research was to test whether any bioactive FQEMs of EF could be synthesized by aerobic fermentation processes using Mycobacterium gilvum (American Tissue Culture Collection) and a mixed culture of microorganisms derived from an agricultural soil. High-performance thin-layer chromatography (HPTLC) and bioautography were tested as screening techniques in the detection and analysis of bioactive FQEMs. MATERIALS AND METHODS: FQEMs derived from M. gilvum and mixed (soil) culture aerobic ferments were fractionated using preparative HPTLC. A standard strain of Escherichia coli was then used as the reporter organism in a bioautography assay in the detection of bioactive-FQEMs on a mid-section of the HPTLC plate. Plate sections were reassembled, and a photograph was taken under low-intensity ultraviolet (UV) light to reveal regions that contained analytes that had UV chromophores and antibacterial-like activities. RESULTS AND DISCUSSION: Many fractionated FQEMs displayed antibacterial-like activity while bound to silica gel HPTLC plates. These results also provide evidence that sufficient quantities of biologically active FQEMs were biologically available from a silica gel surface to prevent the adherent growth of E. coli. Six to seven FQEMs derived from EF using aerobic fermentation processes had antibacterial-like activities, while two FQEMs were also detectable using UV light. Furthermore, similar banding patterns of antibacterial-like activity were observed in both the monoculture (M. gilvum) and mixed culture bioautography assays, indicating that similar processes operated in both aerobic fermentations, either producing similar biologically active FQEMs or biologically active FQEMs that had similar physicochemical properties in both ferments. The simplest explanation for these findings is that the tested agricultural soil also contained mycobacteria that metabolized EF in a similar way to the purchased standard monoculture M. gilvum. Additionally, the marked contrast between the bioautography results and the UV results indicated that the presence of UV chromophores is not a prerequisite for the detection of antibacterial-like activity. CONCLUSIONS: A reliance on spectrophotometric techniques in the detection of bioactive FQEMs in the environment may underestimate component antibacterial-like activity and, possibly, total antibacterial-like activity expressed by EF and its FQEMs. The described bioautography method provides a screening technique with which antibacterial-like activities derived from EF and possibly other FQs can be detected directly on silica gel HPTLC plates. RECOMMENDATIONS: It is recommended that both bioassay and instrumental analytical techniques be used in any measurement of hazard and risk relating to antibacterial-like activities in the environment that are derived from fluoroquinolone antibiotics and their environmental metabolites. PMID- 22311581 TI - Predictive value of FDG PET/CT for pathologic axillary node involvement after neoadjuvant chemotherapy. AB - BACKGROUND: The purpose of this study was to determine the usefulness of sequential FDG PET/CTs for prediction of axillary lymph node (ALN) status after neoadjuvant chemotherapy (NAC). METHODS: Seventy-seven stage II or III breast cancer patients who received 3 cycles of neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this prospective study. FDG PET/CTs were acquired before chemotherapy and after the first cycle of chemotherapy for early metabolic response prediction. RESULTS: Patients with pN0 had significantly lower post-NAC ALN standard uptake value (SUV) than those who were pN+ (1.22 +/- 1.46 in pN0 vs. 2.13 +/- 1.99 in pN+, P = 0.017). Post-NAC ALN size on CT also differed according to pathologic ALN status (6.3 mm in pN0 vs. 11.1 mm in pN+, P = 0.014). When serial FDG PET/CT and chest CT were used, patients with an SUV > 1.5 and post-NAC ALN size >=10 mm on CT did not achieve pN0 (specificity 100% and positive predictive value 100%). CONCLUSIONS: The serial FDG PET/CT after NAC could predict the pathologic status of ALN before surgery in stage II/III breast cancer. Our findings suggest that the combined use of serial FDG PET/CTs and chest CT might provide better information regarding ALN before surgery. PMID- 22311582 TI - Is MRI useful for the prediction of nipple involvement? AB - BACKGROUND: The purpose of this retrospective study was to examine the usefulness of MRI for predicting nipple involvement. METHODS: A retrospective review was performed of 81 breasts in 78 breast cancer patients who had undergone nipple or nipple-areolar complex resections during surgery. The enhancement patterns of the nipple on MRI were compared to the contralateral side and were categorized as no enhancement, bilateral enhancement, and unilateral enhancement. The physical examination results, MRI findings, and pathological findings were assessed. RESULTS: Nipple involvement was observed in 17 of 81 nipples (21%), of which one exhibited infiltration of invasive ductal carcinoma, 12 exhibited ductal carcinoma in situ, and four exhibited Paget's disease. The nipples with no enhancement or with bilateral enhancement on MRI showed a lower rate of nipple involvement than the nipples with unilateral enhancement (0/48 vs. 17/33, p < 0.001). Among the unilaterally enhanced nipples, those with continuous enhancement from the index lesion showed a higher rate of nipple involvement than those without continuous enhancement (16/26 vs. 1/7, p = 0.03). When the enhancement characteristics of the unilaterally enhanced nipples were categorized, the findings with relatively high positive predictive values for nipple involvement were diffuse enhancement (100%, 2/2), unilateral skin enhancement (100%, 2/2), rim enhancement (86%, 6/7), and periductal enhancement (80%, 4/5). CONCLUSIONS: MRI was useful for predicting nipple involvement. Unilateral enhancement of the nipple with continuous enhancement from the index lesion may suggest the possibility of nipple involvement. PMID- 22311583 TI - Prevalence of TP53 germ line mutations in young Pakistani breast cancer patients. AB - Women from Pakistan and India are more often diagnosed with early-onset breast cancer than Caucasian women. Given that only 12% of Pakistani women diagnosed with breast cancer at or before 30 years of age have previously been shown to harbor germ line mutations in the breast cancer susceptibility genes BRCA1 and BRCA2, the genetic causes of the majority of early-onset cases are unexplained. Since germ line mutations in the tumor suppressor gene TP53 predispose women to early-onset breast cancer, we assessed the prevalence of TP53 mutations in 105 early-onset breast cancer patients from Pakistan, who had previously been found to be negative for BRCA1 and BRCA2 germ line mutations. The patient group included 67 women diagnosed with early-onset breast cancer at or before age 30 with no family history of breast or ovarian cancer (EO30NFH group) and 38 women diagnosed with breast cancer at or before age 40 with one or more first- or second-degree relatives with breast or ovarian cancer (EO40FH group). Mutation analysis of the complete TP53 coding region was performed using denaturing high performance liquid chromatography analysis, followed by DNA sequencing of variant fragments. One deleterious mutation, c.499-500delCA in exon 5, was identified in the 105 breast cancer patients (1%). This mutation is novel in the germ line and has not been described in other populations. It was detected in a 28-year-old patient with no family history of breast or ovarian cancer. This mutation is rare as it was not detected in additional 157 recently recruited non-BRCA1 and non BRCA2-associated early-onset breast cancer patients. Our findings show that TP53 mutations may account for a minimal portion of early-onset breast cancer in Pakistan. PMID- 22311584 TI - Psychological distress in newly diagnosed colorectal cancer patients following microsatellite instability testing for Lynch syndrome on the pathologist's initiative. AB - According to the Dutch Guideline on Hereditary Colorectal Cancer published in 2008, patients with recently diagnosed colorectal cancer (CRC) should undergo microsatellite instability (MSI) testing by a pathologist immediately after tumour resection if they are younger than 50 years, or if a second CRC has been diagnosed before the age of 70 years, owing to the high risk of Lynch syndrome (MIPA). The aim of the present MIPAPS study was to investigate general distress and cancer-specific distress following MSI testing. From March 2007 to September 2009, 400 patients who had been tested for MSI after newly diagnosed CRC were recruited from 30 Dutch hospitals. Levels of general distress (SCL-90) and cancer specific distress (IES) were assessed immediately after MSI result disclosure (T1) and 6 months later (T2). Response rates were 23/77 (30%) in the MSI-positive patients and 58/323 (18%) in the MSI-negative patients. Levels of general distress and cancer-specific distress were moderate. In the MSI-positive group, 27% of the patients had high general distress at T1 versus 18% at T2 (p = 0.5), whereas in the MSI-negative group, these percentage were 14 and 18% (p = 0.6), respectively. At T1 and T2, cancer-specific distress rates in the MSI-positive group and MSI-negative group were 39 versus 27% (p = 0.3) and 38 versus 36% (p = 1.0), respectively. High levels of general distress were correlated with female gender, low social support and high perceived cancer risk. Moderate levels of distress were observed after MSI testing, similar to those found in other patients diagnosed with CRC. Immediately after result disclosure, high cancer specific distress was observed in 40% of the MSI-positive patients. PMID- 22311585 TI - Discovery of novel 2-N-aryl-substituted benzenesulfonamidoacetamides: orally bioavailable tubulin polymerization inhibitors with marked antitumor activities. AB - The discovery and optimization of a series of 2-N-aryl-substituted benzenesulfonamidoacetamides as novel tubulin polymerization inhibitors are described. Pharmacophore exploration of hit compound AH-487 identified the optimal structure of N-heteroaryl-2-(4-methoxy-N-(3 (trifluoromethyl)phenyl)phenylsulfonamido)acetamide as a potent antimitotic agent. Subsequent lead compounds 4b and 4c, with N-4-aminophenyl and N-1H-indol-5 yl substitutions at the acetamide position, respectively, were shown to induce cell-cycle arrest at the G(2) /M phase and lead to an accumulation of HeLa cells in the sub-G(1) phase. More significantly, these lead compounds (3c, 4b, and 4c) exhibit impressive cytotoxicity against a panel of cancer cells including P glycoprotein-overexpressing MDR-positive cells, with potency greater than or equal to clinically studied benzenesulfonamide E7010. Mechanistic studies demonstrated that derivatives of AH-487 disrupt mitotic spindles by inhibiting microtubule polymerization and induce apoptosis via induction of Bcl-2 phosphorylation in tumor cells. The optimized leads 4b and 4c strongly inhibited the growth of human hepatocellular carcinoma cells in a mouse xenograft model. PMID- 22311586 TI - The potential utility of the leopard pleco (Glyptoperichthys gibbiceps) as a biological control of the ciliate protozoan Ichthyophthirius multifiliis. AB - BACKGROUND: Infections of the ciliate protozoan Ichthyophthirius multifiliis Fouquet, 1876, can cause heavy mortalities in freshwater aquaculture systems. Following the ban of malachite green on fish for human consumption, currently available chemical therapies are only partially efficacious even when repeatedly applied. There is, therefore, an urgent necessity to identify more efficient and environmentally friendly control strategies. In the present study, the use of a substrate algae feeder leopard pleco, Glyptoperichthys gibbiceps, as a biological agent to control I. multifiliis infections on blue tilapia, Oreochromis aureus, reared in a warm-water, experimental tank-based system is explored. RESULTS: The free-swimming protomont stage of I. multifiliis demonstrated selective settlement behaviour towards biofilm-covered substrates. Following a controlled exposure, the number of I. multifiliis trophonts establishing on naive blue tilapia, O. aureus, was 4.9 +/- 0.4 when reared with G. gibbiceps, significantly lower than when reared in isolation (13.3 +/- 0.9; ANOVA, P < 0.001). CONCLUSION: This study demonstrates for the first time the potential of G. gibbiceps as a biological control to reduce I. multifiliis on commercially valuable fish stocks in warm water systems. This likely originated from the grazing activity of G. gibbiceps on the biofilm layer upon which the multiplicative stage of I. multifiliis was shown preferentially to settle. Therapeutic strategies against pathogenic protozoan species like I. multifiliis could greatly benefit from incorporating, where appropriate, a biological control targeting the external multiplicative life stages of the parasite, potentially reducing the current dependence on chemical interventions. PMID- 22311587 TI - Antiviral therapy of respiratory viruses in haematopoietic stem cell transplant recipients. AB - The treatment of respiratory viruses is extremely challenging in haematopoietic stem cell transplant (HSCT) recipients. Outcomes related to these infections have improved over the past decade. More recently, studies have looked at respiratory virus epidemiology using molecular assays to understand the wide range of diseases in HSCT recipients. The emergence of pandemic H1N1 in 2009 encouraged implementation of molecular assays in many clinical laboratories and broadened influenza resistance detection. Finally, new drugs have been developed to treat influenza virus, respiratory syncytial virus, parainfluenza virus and adenovirus with some promising results. PMID- 22311588 TI - Anammox enrichment from reject water on blank biofilm carriers and carriers containing nitrifying biomass: operation of two moving bed biofilm reactors (MBBR). AB - The anammox bacteria were enriched from reject water of anaerobic digestion of municipal wastewater sludge onto moving bed biofilm reactor (MBBR) system carriers-the ones initially containing no biomass (MBBR1) as well as the ones containing nitrifying biomass (MBBR2). Duration of start-up periods of the both reactors was similar (about 100 days), but stable total nitrogen (TN) removal efficiency occurred earlier in the system containing nitrifying biomass. Anammox TN removal efficiency of 70% was achieved by 180 days in both 20 l volume reactors at moderate temperature of 26.0 degrees C. During the steady state phase of operation of MBBRs the average TN removal efficiencies and maximum TN removal rates in MBBR1 were 80% (1,000 g-N/m(3)/day, achieved by 308 days) and in MBBR2 85% (1,100 g-N/m(3)/day, achieved by 266 days). In both reactors mixed bacterial cultures were detected. Uncultured Planctomycetales bacterium clone P4, Candidatus Nitrospira defluvii and uncultured Nitrospira sp. clone 53 were identified by PCR-DGGE from the system initially containing blank biofilm carriers as well as from the nitrifying biofilm system; from the latter in addition to these also uncultured ammonium oxidizing bacterium clone W1 and Nitrospira sp. clone S1-62 were detected. FISH analysis revealed that anammox microorganisms were located in clusters in the biofilm. Using previously grown nitrifying biofilm matrix for anammox enrichment has some benefits over starting up the process from zero, such as less time for enrichment and protection against severe inhibitions in case of high substrate loading rates. PMID- 22311589 TI - Biodegradation of organic compounds of molasses melanoidin (MM) from biomethanated distillery spent wash (BMDS) during the decolourisation by a potential bacterial consortium. AB - Molasses melanoidin (MM) is a major pollutant in biomethanated distillery spent wash (BMDS) due to its recalcitrant properties. The 75% colour and 71% COD of MM (1,000 ppm) were reduced with developed bacterial consortium comprising Proteus mirabilis (IITRM5; FJ581028), Bacillus sp. (IITRM7; FJ581030), Raoultella planticola (IITRM15; GU329705) and Enterobacter sakazakii (IITRM16, FJ581031) in the ratio of 4:3:2:1 within 10 days at optimized nutrient. Bacterial consortium showed manganese peroxidase and laccase activity during MM decolourisation. The dominant growth of R. planticola and E. sakazakii was noted in consortium during MM decolourisation. The comparative GC-MS analysis of extracted compounds of control and degraded samples showed that most of the compounds present in control were completely utilized by bacterial consortium along with production of some metabolites. The developed bacterial consortium could be a tool for the decolourisation and degradation of melanoidin containing BMDS. PMID- 22311590 TI - Long-term simulation of in situ biostimulation of polycyclic aromatic hydrocarbon contaminated soil. AB - A continuous-flow column study was conducted to evaluate the long-term effects of in situ biostimulation on the biodegradation of polycyclic aromatic hydrocarbons (PAHs) in soil from a manufactured gas plant site. Simulated groundwater amended with oxygen and inorganic nutrients was introduced into one column, while a second column receiving unamended groundwater served as a control. PAH and dissolved oxygen (DO) concentrations, as well as microbial community profiles, were monitored along the column length immediately before and at selected intervals up to 534 days after biostimulation commenced. Biostimulation resulted in significantly greater PAH removal than in the control condition (73% of total measured PAHs vs. 34%, respectively), with dissolution accounting for a minor amount of the total mass loss (~6%) in both columns. Dissolution was most significant for naphthalene, acenaphthene, and fluorene, accounting for >20% of the total mass removed for each. A known group of PAH-degrading bacteria, 'Pyrene Group 2' (PG2), was identified as a dominant member of the microbial community and responded favorably to biostimulation. Spatial and temporal variations in soil PAH concentration and PG2 abundance were strongly correlated to DO advancement, although there appeared to be transport of PG2 organisms ahead of the oxygen front. At an estimated oxygen demand of 6.2 mg O(2)/g dry soil and a porewater velocity of 0.8 m/day, it took between 374 and 466 days for oxygen breakthrough from the 1-m soil bed in the biostimulated column. This study demonstrated that the presence of oxygen was the limiting factor in PAH removal, as opposed to the abundance and/or activity of PAH-degrading bacteria once oxygen reached a previously anoxic zone. PMID- 22311591 TI - Simultaneous biodegradation of phenol and carbon tetrachloride mediated by humic acids. AB - The capacity of an anaerobic sediment to achieve the simultaneous biodegradation of phenol and carbon tetrachloride (CT) was evaluated, using humic acids (HA) as redox mediator. The presence of HA in sediment incubations increased the rate of biodegradation of phenol and the rate of dehalogenation (2.5-fold) of CT compared to controls lacking HA. Further experiments revealed that the electron-accepting capacity of HA derived from different organic-rich environments was not associated with their reducing capacity to achieve CT dechlorination. The collected kinetic data suggest that the reduction of CT by reduced HA was the rate-limiting step during the simultaneous biodegradation of phenol and CT. To our knowledge, the present study constitutes the first demonstration of the simultaneous biodegradation of two priority pollutants mediated by HA. PMID- 22311592 TI - Pulmonary veno-occlusive disease: a misnomer? AB - Pulmonary veno-occlusive disease (PVOD) is a rare entity with non-specific signs and symptoms and is nearly always associated with a dismal prognosis. This review will first consider pulmonary hypertension in general and then will focus on PVOD specifically with particular attention to the pathophysiology of the disease. Classically PVOD is described as a disease primarily involving obstructed venules, with the arterial side of the circulation involved to a lesser degree. This article discusses the demographics of affected individuals; the ways in which an accurate diagnosis can be made, including imaging features; predisposing diseases and associated disorders; and potential treatment. PMID- 22311593 TI - Detection of multiple autoantibodies in patients with ankylosing spondylitis using nucleic acid programmable protein arrays. AB - Ankylosing spondylitis (AS) is a common, inflammatory rheumatic disease that primarily affects the axial skeleton and is associated with sacroiliitis, uveitis, and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine whether plasma from patients with AS contained autoantibodies and, if so, characterize and quantify this response in comparison to patients with rheumatoid arthritis (RA) and healthy controls. Two high density nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA, and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis to determine the patterns of signaling cascades or tissue origin. 44% of patients with ankylosing spondylitis demonstrated a broad autoantibody response, as compared with 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The autoantibody responses in the AS patients were targeted toward connective, skeletal, and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic acid programmable protein arrays constitute a powerful tool to study autoimmune diseases. PMID- 22311594 TI - Solution-processed ultrathin chemically derived graphene films as soft top contacts for solid-state molecular electronic junctions. AB - A novel method using solution-processed ultrathin chemically derived graphene films as soft top contacts for the non-destructive fabrication of molecular junctions is demonstrated. We believe this protocol will greatly enrich the solid state test beds for molecular electronics due to its low-cost, easy-processing and flexible nature. PMID- 22311595 TI - Current state of diagnosis and management of critical limb ischemia. AB - Critical limb ischemia represents the most severe form of peripheral arterial disease and carries with it severe morbidity and mortality risks. Because of comorbidity risks, early diagnosis and aggressive medical management make up an important part of the treatment paradigm for these individuals. However, in addition to managing these comorbid conditions, the physician caring for these individuals must be able to provide revascularization options that will improve arterial flow to the threatened extremity and assure healing of complicated wounds. Both open surgical and endovascular therapies have proven beneficial in restoring flow to severely ischemic limbs in these patients. Additionally, combinations of the above therapeutic methods have offered more available options for these patients. This article reviews care of patients with critical limb ischemia with critical assessment of options for medical and revascularization options. PMID- 22311596 TI - The comparative research on constituents of Radix Aconiti and its processing by HPLC quadrupole TOF-MS. AB - Based upon the regulations stipulated by the State Food and Drug Administration of China, only the processed, detoxified tubers and roots of Aconitum are allowed to be administered orally, used in clinical decoctions and adopted as raw materials for pharmaceutical manufacturing, so the processing principle of preparation of Radix Aconiti is important for ensuring the Radix Aconiti praeparata quality. A simple approach was described for HPLC-Q-TOF-MS screening and identification of many of the aconitine alkaloids present in unprocessed Radix Aconiti and Radix Aconiti praeparata. To compare their fingerprints, the processing principle of preparation of Radix Aconiti was developed. Twenty-nine compounds and 26 compounds were assigned to aconitine alkaloids and tentatively identified by comparing accurate mass and fragments information with that of the authentic standards or by mass spectrometry analysis and retrieving the reference literature. The nonester alkaloids were almost the same. The diester diterpene alkaloids were decreased, the monoester-diterpene alkaloids were increased and lipo-alkaloids decreased obviously in the processing of the preparation. These transformed components could be regarded as potential chemical markers that can be used to distinguish between raw and processed herbs. PMID- 22311597 TI - Rod-shaped Fe2O3 as an efficient catalyst for the selective reduction of nitrogen oxide by ammonia. PMID- 22311598 TI - Leishmania amazonensis impairs DC function by inhibiting CD40 expression via A2B adenosine receptor activation. AB - Dendritic cells (DCs) play an essential role in the modulation of immune responses and several studies have evaluated the interactions between Leishmania parasites and DCs. While extracellular ATP exhibits proinflammatory properties, adenosine is an important anti-inflammatory mediator. Here we investigated the effects of Leishmania infection on DC responses and the participation of purinergic signalling in this process. Bone marrow-derived dendritic cells (BMDCs) from C57BL/6J mice infected with Leishmania amazonensis, Leishmania braziliensis or Leishmania major metacyclic promastigotes showed decreased major histocompatibility complex (MHC) class II and CD86 expression and increased ectonucleotidase expression as compared with uninfected cells. In addition, L. amazonensis-infected DCs, which had lower CD40 expression, exhibited a decreased ability to induce T-cell proliferation. The presence of MRS1754, a highly selective A(2B) adenosine receptor antagonist at the time of infection increased MHC class II, CD86 and CD40 expression in L. amazonensis-infected DCs and restored the ability of the infected DCs to induce T-cell proliferation. Similar results were obtained through the inhibition of extracellular ATP hydrolysis using suramin. In conclusion, we propose that A(2B) receptor activation may be used by L. amazonensis to inhibit DC function and evade the immune response. PMID- 22311599 TI - Synapse loss induced by interleukin-1beta requires pre- and post-synaptic mechanisms. AB - Interleukin-1beta (IL-1beta) is an inflammatory cytokine that exerts marked effects on neuronal function and survival. Here we examined the effects of IL 1beta on synapses between rat hippocampal neurons in culture using an imaging based assay to quantify clusters of the scaffolding protein postsynaptic density 95 fused to green fluorescent protein. Treatment with IL-1beta for 24 h induced a 23 +/- 3% loss in the number of synaptic sites. Pharmacological studies indicated that synapse loss was mediated by the IL-1 receptor with subsequent activation of two pathways. COX2-mediated prostaglandin production and postsynaptic activation of a Src family tyrosine kinase were required. Presynaptic release of glutamate with subsequent activation of NMDA receptors was necessary for IL-1beta-induced synapse loss. Neither Src activation nor prostaglandin E2 (PGE2) application alone was sufficient to reduce the number of synapses. However, in cells expressing constitutively active or pharmacologically activated Src, PGE2 induced synapse loss. Thus, IL-1beta reduces the number of synaptic connections by simultaneously activating multiple pathways that require both pre- and post synaptic activity. These results highlight targets that may prove important for pharmacotherapy of neuroinflammatory disease. PMID- 22311600 TI - Tyrosine impairs enzymes of energy metabolism in cerebral cortex of rats. AB - Tyrosine levels are abnormally elevated in tissues and physiological fluids of patients with inborn errors of tyrosine catabolism, especially in tyrosinemia type II, which is caused by deficiency of tyrosine aminotransferase and provokes eyes, skin, and central nervous system disturbances. Considering that the mechanisms of brain damage in these disorders are poorly known, in this study, we investigated the in vivo and in vitro effects of tyrosine on some parameters of energy metabolism in cerebral cortex of 14-day-old Wistar rats. We observed that 2 mM tyrosine inhibited in vitro the pyruvate kinase (PK) activity and that this inhibition was prevented by 1 mM reduced glutathione with 30, 60, and 90 min of preincubation. Moreover, administration of tyrosine methyl ester (TME) (0.5 mg/g of body weight) decreased the activity of PK and this reduction was prevented by pre-treatment with creatine (Cr). On the other hand, tyrosine did not alter adenylate kinase (AK) activity in vitro, but administration of TME enhanced AK activity not prevented by Cr pre-treatment. Finally, TME administration decreased the activity of CK from cytosolic and mitochondrial fractions and this diminution was prevented by Cr pre-treatment. The results suggest that tyrosine alters essential sulfhydryl groups necessary for CK and PK functions, possibly through oxidative stress. In case this also occurs in the patients, it is possible that energy metabolism alterations may contribute, along with other mechanisms, to the neurological dysfunction of hypertyrosinemias. PMID- 22311602 TI - Sexual patterns and protogynous sex reversal in the rusty parrotfish, Scarus ferrugineus (Scaridae): histological and physiological studies. AB - Gonadal histology confirmed that Scarus ferrugineus is a diandric protogynous fish. The process of protogynous sex reversal was investigated through histological observations on the gonads of females changing sex to male. This process was divided into three stages on the basis of changes in the structure of the germinal and somatic elements. Ovaries of functional females (stages IV-V) were filled with vitellogenic oocytes during the breeding season but contained no trace of spermatogenic tissue. During post-spawning period, the remaining vitellogenic oocytes began to degenerate and accompanied by a drop in plasma levels of estradiol-17beta. At the commencement of sex change, previtellogenic oocytes began to degenerate and stromal cell aggregation was observed in the central region of the lamellae. At mid-reversal stage, steroid-producing cells (Leydig cells) developed at the border of the stromal aggregate and spermatogonial cysts appear at the periphery of lamellae. Finally, sex change to secondary males was considered complete, with the beginning of active spermatogenesis and spermiation. Plasma levels of testosterone remained low throughout the sex change, but II-KT increased rapidly parallel to the increased number of Leydig cells while the level of estradiol-17beta decreased. The results indicate also that the sex-changed males had higher level of II-KT than primary males, while primary males had higher level of testosterone. Histological examination revealed that testes of primary and secondary males are almost identical in organization of the spermatogenic cysts, association of sertoli cells, and developing germ cells but differ in clustering and development of Leydig cells. PMID- 22311601 TI - Antioxidant activity of beta-selenoamines and their capacity to mimic different enzymes. AB - The antioxidant properties of organoselenium compounds have been extensively investigated because oxidative stress is a hallmark of a variety of chronic human diseases. Here, we reported the influence of substituent groups in the antioxidant activity of beta-selenoamines. We have investigated whether they exhibited glutathione peroxidase-like (GPx-like) activity and whether they could be substrate of thioredoxin reductase (TrxR). In the DPPH assay, the beta selenium amines did not exhibit antioxidant activity. However, the beta-selenium amines with p-methoxy and tosyl groups prevented the lipid peroxidation. The beta selenium amine compound with p-methoxy substituent group exhibited thiol peroxidase-like activity (GPx-like activity) and was reduced by the hepatic TrxR. These results contribute to understand the influence of structural alteration of non-conventional selenium compounds as synthetic mimetic of antioxidant enzymes of mammalian organisms. PMID- 22311603 TI - Stabilization of high-valence ruthenium with silicotungstate ligands: preparation, structural characterization, and redox studies of ruthenium(III) substituted alpha-Keggin-type silicotungstates with pyridine ligands, [SiW11O39Ru(III)(Py)]5-. AB - Ruthenium(III)-substituted alpha-Keggin-type silicotungstates with pyridine-based ligands, [SiW(11)O(39)Ru(III)(Py)](5-), (Py: pyridine (1), 4-pyridine-carboxylic acid (2), 4,4'-bipyridine (3), 4-pyridine-acetamide (4), and 4-pyridine-methanol (5)) were prepared by reacting [SiW(11)O(39)Ru(III)(H(2)O)](5-) with the pyridine derivatives in water at 80 degrees C and then isolated as their hydrated cesium salts. These compounds were characterized using cyclic voltammetry (CV), UV/Vis, IR, and (1)H NMR spectroscopy, elemental analysis, titration, and X-ray absorption near-edge structure (XANES) analysis (Ru K-edge and L(3)-edge). Single crystal X-ray analysis of compounds 2, 3, and 4 revealed that Ru(III) was incorporated in the alpha-Keggin framework and was coordinated by pyridine derivatives through a Ru-N bond. In the solid state, compounds 2 and 3 formed a dimer through pi-pi interaction of the pyridine moieties, whereas they existed as monomers in solution. CV indicated that the incorporated Ru(III)-Py was reversibly oxidized into the Ru(IV)-Py derivative and reduced into the Ru(II)-Py derivative. PMID- 22311604 TI - Rifabutin-associated hypopyon uveitis and retinal vasculitis with a history of acute myeloid leukemia. AB - PURPOSE: This study reports a case of bilateral rifabutin-associated uveitis in a child with a history of acute myeloid leukemia. METHODS: We utilized a clinical case description and brief discussion. RESULTS: A 17-year-old girl presented with acute bilateral anterior uveitis, a hypopyon in the left eye, and moderate bilateral vitritis. She had a history of acute myeloid leukemia status post allogeneic hematopoietic stem cell transplant 5 years earlier. She was receiving rifabutin for a biopsy-proven Mycobacterium avium complex pulmonary infection. Work up for infectious and neoplastic etiologies was negative. The uveitis initially responded to topical corticosteroids, but recurred when the drops were tapered. Fluorescein angiography demonstrated diffuse vasculitis of small retinal vessels and cystoid macular edema. After rifabutin was discontinued, the uveitis and vasculitis slowly resolved. CONCLUSION: Fluorescein angiography demonstrated widespread retinal vasculitis which is a rare manifestation of rifabutin associated uveitis. PMID- 22311606 TI - Study of intermolecular contacts in the proline-rich homeodomain (PRH)-DNA complex using molecular dynamics simulations. AB - The proline-rich homeodomain (PRH)-DNA complex consists of a protein with 60 residues and a 13-base-pair DNA. The PRH protein is a transcription factor that plays a key role in the regulation of gene expression. PRH is a significant member of the Q50 class of homeodomain proteins. The homeodomain section of PRH is essential for binding to DNA and mediates sequence-specific DNA binding. Three 20-ns molecular dynamics (MD) simulations (free protein, free DNA and protein-DNA complex) in explicit solvent water were performed to elucidate the intermolecular contacts in the PRH-DNA complex and the role of dynamics of water molecules forming water-mediated contacts. The simulation provides a detailed explanation of the trajectory of hydration water molecules. The simulations show that some water molecules in the protein-DNA interface exchange with bulk waters. The simulation identifies that most of the contacts consisted of direct interactions between the protein and DNA including specific and non-specific contacts, but several water-mediated polar contacts were also observed. The specific interaction between Gln50 and C18 and water-mediated hydrogen bond between Gln50 and T7 were found to be present during almost the entire time of the simulation. These results show good consistency with experimental and previous computational studies. Structural properties such as root-mean-square deviations (RMSD), root mean-square fluctuations (RMSF) and secondary structure were also analyzed as a function of time. Analyses of the trajectories showed that the dynamic fluctuations of both the protein and the DNA were lowered by the complex formation. PMID- 22311607 TI - Antibodies for prevention and treatment of respiratory syncytial virus infections in children. AB - Respiratory syncytial virus (RSV) infection causes respiratory illness in all ages, and is the leading cause of hospitalizations of infants and children around the world. Those at increased risk for severe disease include infants with congenital heart disease, premature infants, children with neuromuscular disease, airway abnormalities, underlying immunodeficiencies and the elderly. Attempts to develop a safe and effective vaccine have been unsuccessful thus far. However, significant progress has been achieved in the field of passive immunoprophylaxis for protection against RSV. This review will concentrate on the past, present and future history of RSV immunoprophylaxis with an emphasis on the role of polyclonal and monoclonal antibodies. PMID- 22311608 TI - Poly(N-vinyl-2-pyrrolidone) elution from polysulfone dialysis membranes by varying solvent and wall shear stress. AB - Some dialysis patients are treated with post-hemodiafiltration (HDF); the blood viscosity of the patients who undergo post-HDF is higher than that of the patients who undergo conventional hemodialysis. This study aims to evaluate poly(N-vinyl-2-pyrrolidone) (PVP) elution from PSf dialysis membranes by varying solvents and high wall shear stress caused by blood viscosity. We tested three commercial membranes: APS-15SA (Asahi Kasei Kuraray), CX-1.6U (Toray) and FX140 (Fresenius). Dialysate and blood sides of the dialyzers were primed with reverse osmosis (RO) water and saline. RO water, saline and dextran solution (2.9 and 5.8 mPa s) were circulated in the blood side. The amount of eluted PVP was determined by 0.02 N iodometry. The hardness and adsorption force of human serum albumin (HSA) on the membrane surfaces were measured by the atomic force microscope. When wall shear stress was increased using dextran, the amount of PVP eluted by the 2.9 mPa s solution equaled that eluted by the 5.8 mPa s solution with APS-15SA and CX-1.6U sterilized by gamma rays. The amount of PVP eluted by the 5.8 mPa s solution was higher than that eluted by the 2.9 mPa s solution with FX140 sterilized by autoclaving. The wall shear stress increased the PVP elution from the surface, hardness and adsorption force of HSA. Sufficient gamma-ray irradiation is effective in decreasing PVP elution. PMID- 22311609 TI - Transculturalization of a diabetes-specific nutrition algorithm: Asian application. AB - The prevalence of type 2 diabetes (T2D) in Asia is growing at an alarming rate, posing significant clinical and economic risk to health care stakeholders. Commonly, Asian patients with T2D manifest a distinctive combination of characteristics that include earlier disease onset, distinct pathophysiology, syndrome of complications, and shorter life expectancy. Optimizing treatment outcomes for such patients requires a coordinated inclusive care plan and knowledgeable practitioners. Comprehensive management starts with medical nutrition therapy (MNT) in a broader lifestyle modification program. Implementing diabetes-specific MNT in Asia requires high-quality and transparent clinical practice guidelines (CPGs) that are regionally adapted for cultural, ethnic, and socioeconomic factors. Respected CPGs for nutrition and diabetes therapy are available from prestigious medical societies. For cost efficiency and effectiveness, health care authorities can select these CPGs for Asian implementation following abridgement and cultural adaptation that includes: defining nutrition therapy in meaningful ways, selecting lower cutoff values for healthy body mass indices and waist circumferences (WCs), identifying the dietary composition of MNT based on regional availability and preference, and expanding nutrition therapy for concomitant hypertension, dyslipidemia, overweight/obesity, and chronic kidney disease. An international task force of respected health care professionals has contributed to this process. To date, task force members have selected appropriate evidence-based CPGs and simplified them into an algorithm for diabetes-specific nutrition therapy. Following cultural adaptation, Asian and Asian-Indian versions of this algorithmic tool have emerged. The Asian version is presented in this report. PMID- 22311610 TI - A synergy between incretin effect and intestinal gluconeogenesis accounting for the rapid metabolic benefits of gastric bypass surgery. AB - The early improvement of glucose control taking place shortly after gastric bypass surgery in obese diabetic patients has long been mysterious. A recent study in mice has highlighted some specific mechanisms underlying this phenomenon. The specificity of gastric bypass in obese diabetic mice relates to major changes in the sensations of hunger and to rapid improvement of glucose parameters. The induction of intestinal gluconeogenesis plays a major role in diminishing hunger, and in restoring insulin sensitivity of endogenous glucose production. In parallel, the restoration of the secretion of glucagon-like peptide 1 and insulin plays a key additional role, in this context of recovered insulin sensitivity, to improve postprandial glucose tolerance. Therefore, a synergy between an incretin effect and intestinal gluconeogenesis is a key feature accounting for the rapid improvement of glucose control in obese diabetic patients after bypass surgery. PMID- 22311611 TI - Mimicry between mitochondrial disorder and multiple sclerosis. AB - Under certain conditions or at certain stages of the disease course, multiple sclerosis (MS) and mitochondrial disorder (MID) may be differential diagnoses and thus may be confused with each other. In a 30 years old female MS was diagnosed at age 16 year upon recurrent sensory disturbances of the right lower leg, an "inflammatory" cerebrospinal fluid, and a cerebral MRI with multiple non enhancing white matter lesions. Steroids were repeatedly given but because of rapid deterioration treatment was switched to interferon and mitoxantrone, without improvement. Fourteen years after onset the patient additionally presented with a history of rhabdomyolysis, hypothyroidism, ophthalmoparesis, anarthria, tetraspasticity, tetraparesis, and joint contractures. After MID had been diagnosed in her mother she was re-evaluated and elevated resting lactate, axonal polyneuropathy, and empty sella were additionally found. Muscle biopsy revealed myophagy, fat deposition, and type-II predominance, and biochemical investigations showed a deficiency of complex I and IV of the respiratory chain. MID was diagnosed also in the index patient. It is concluded that even if CSF investigations or imaging studies suggest MS, differentials such as MIDs need to be excluded before prescribing medication possibly toxic to a MID. An "inflammatory CSF" may also occur in MIDs. PMID- 22311612 TI - Simultaneous determination of atractylenolide II and atractylenolide III by liquid chromatography-tandem mass spectrometry in rat plasma and its application in a pharmacokinetic study after oral administration of Atractylodes Macrocephala Rhizoma extract. AB - Atractylenolide II (AII) and atractylenolide III (AIII) are the major active components in Atractylodes Macrocephala Rhizoma (AMR). In this study, a sensitive, rapid and selective liquid chromatography-tandem mass spectrometry (LC MS/MS) method was developed and validated for the simultaneous determination of AII and AIII in rat plasma using loliolide as internal standard (IS). After protein precipitation with ethyl acetate, the analytes were injected into an LC MS/MS system for quantification. Chromatography was performed using a C(18) column, eluting with water and acetonitrile (45:55, v/v) at 0.2 mL/min. All analytes including IS were monitored under positive ionization conditions by multiple reaction monitoring with an electrospray ionization source. The validated method was successfully applied to the pharmacokinetic study of AII and AIII in rat plasma after oral administration of AMR extract. The results provided a meaningful basis for evaluating the clinical applications of traditional Chinese medicine. PMID- 22311613 TI - Structural characterization of neutral and acidic oligosaccharides in the milks of strepsirrhine primates: greater galago, aye-aye, Coquerel's sifaka and mongoose lemur. AB - The structures of milk oligosaccharides were characterized for four strepsirrhine primates to examine the extent to which they resemble milk oligosaccharides in other primates. Neutral and acidic oligosaccharides were isolated from milk of the greater galago (Galagidae: Otolemur crassicaudatus), aye-aye (Daubentoniidae: Daubentonia madagascariensis), Coquerel's sifaka (Indriidae: Propithecus coquereli) and mongoose lemur (Lemuridae: Eulemur mongoz), and their chemical structures were characterized by (1)H-NMR spectroscopy. The oligosaccharide patterns observed among strepsirrhines did not appear to correlate to phylogeny, sociality or pattern of infant care. Both type I and type II neutral oligosaccharides were found in the milk of the aye-aye, but type II predominate over type I. Only type II oligosaccharides were identified in other strepsirrhine milks. alpha3'-GL (isoglobotriose, Gal(alpha1-3)Gal(beta1-4)Glc) was found in the milks of Coquerel's sifaka and mongoose lemur, which is the first report of this oligosaccharide in the milk of any primate species. 2'-FL (Fuc(alpha1-2)Gal(beta1 4)Glc) was found in the milk of an aye-aye with an ill infant. Oligosaccharides containing the Lewis x epitope were found in aye-aye and mongoose lemur milk. Among acidic oligosaccharides, 3'-N-acetylneuraminyllactose (3'-SL-NAc, Neu5Ac(alpha2-3)Gal(beta1-4)Glc) was found in all studied species, whereas 6'-N acetylneuraminyllactose (6'-SL-NAc, Neu5Ac(alpha2-6)Gal(beta1-4)Glc) was found in all species except greater galago. Greater galago milk also contained 3'-N glycolylneuraminyllactose (3'-SL-NGc, Neu5Gc(alpha2-3)Gal(beta1-4)Glc). The finding of a variety of neutral and acidic oligosaccharides in the milks of strepsirrhines, as previously reported for haplorhines, suggests that such constituents are ancient rather than derived features, and are as characteristic of primate lactation is the classic disaccharide, lactose. PMID- 22311614 TI - Extrusion of CO from aryl ketones: rhodium(I)-catalyzed C-C bond cleavage directed by a pyridine group. AB - Snipping tool: the rhodium(I)-catalyzed extrusion of carbon monoxide from biaryl ketones and alkyl/alkenyl aryl ketones was developed to produce biaryls and alkyl/alkenyl arenes, respectively, in high yields. A wide range of functionalities are tolerated. Not only does this method provide an alternative pathway to construct useful scaffolds, but also offers a new strategy for C-C bond activation. PMID- 22311615 TI - Pregnancy and drinking among women offenders under community supervision in the United States: 2004-2008. AB - Drinking during pregnancy raises risks of pregnancy, labor, and delivery complications in mothers and lasting neurological or behavioral consequences in babies. This public health issue has recently attracted the attention of criminal justice (CJ) researchers, as the prevalence of Fetal Alcohol Spectrum Disorders (FASDs) appears to be unusually high among offender populations. Nevertheless, in addition to becoming a main caretaker of individuals with FASDs, the CJ system already may have under its care some of the women at the highest risk of drinking during pregnancy. This study sets out to determine the prevalence, patterns, and correlates of alcohol consumption among women offenders on probation or parole in the United States. Analysis of data collected from seven waves of the National Survey on Drug Use and Health (2004-2008) were performed on women who were under community supervision during the year prior to the survey interview. Results revealed that 1.9% of women of child-bearing ages of 12-44 years in the general population were pregnant, as compared to 4.7% of comparable women under community supervision. Pregnant offenders were more likely to come from minority groups and be socially disadvantaged than their non-CJ-involved counterparts. Alarmingly, they were nearly three times as likely to have engaged in problem drinking (e.g., two drinks a day for a month) than non-CJ-involved women. Negative behavioral consequences resulting from alcohol consumption and concurrent use of other substances were also significantly more pervasive among drinkers under community supervision. Effective prevention and control of the problem requires rethinking the role of corrections systems in health promotion. Concrete recommendations are discussed. PMID- 22311616 TI - Experimental human influenza: observations from studies of influenza antivirals. AB - Randomized, placebo-controlled trials have been conducted for nearly five decades in experimentally induced human influenza infections to assess the effectiveness, tolerability and pharmacological properties of influenza antivirals. The results of such studies have not only provided key proof-of-concept data to facilitate drug development but also contributed to our understanding of influenza pathogenesis and transmission. The lack of availability of contemporary, safety tested virus inoculation pools in recent years needs to be resolved in order to avoid hindering the development of new drugs and vaccines. PMID- 22311617 TI - Protein kinase D isoforms are dispensable for integrin-mediated lymphocyte adhesion and homing to lymphoid tissues. AB - Leukocyte function-associated antigen-1 (LFA-1) and very late antigen-4 (VLA-4) integrins are essential for lymphocyte adhesion, trafficking and effector functions. Protein kinase D (PKD) has previously been implicated in lymphocyte integrin regulation through regulation of Rap1 activity. However, the true role of PKD in integrin regulation in primary lymphocytes has not previously been investigated. The major PKD isoform in lymphocytes is PKD2. Here we employed PKD2 deficient mice, a specific PKD kinase inhibitor, as well as PKD-null DT40 B cells to investigate the role of PKD in integrin regulation in lymphocytes. We report that PKD2-deficient lymphocytes bound normally to integrin ligands in static and shear flow adhesion assays. They also homed normally to lymphoid organs after adoptive transfer into wild-type mice. DT40 B cells devoid of any PKD isoforms and primary lymphocytes pretreated with a specific PKD inhibitor bound normally to integrin ligands, indicating that multiple PKD isoforms do not redundantly regulate lymphocyte integrins. In addition, PKD2-deficient lymphocytes, as well as DT40 cells devoid of any PKD isoforms, could activate Rap1 in response to B cell receptor ligation or phorbol ester treatment. Together, these results show that the PKD family does not play a critical role in lymphocyte integrin-mediated cell adhesion or lymphocyte trafficking in vivo. PMID- 22311618 TI - Effect of in utero wi-fi exposure on the pre- and postnatal development of rats. AB - BACKGROUND: The increase in exposure to the Wireless Fidelity (Wi-Fi) wireless communication signal has raised public health concerns especially for young people. Animal studies looking at the effects of early life and prenatal exposure to this source of electromagnetic fields, in the radiofrequency (RF) range, on development and behavior have been considered as high priority research needs by the World Health Organization. METHODS: For the first time, our study assessed the effects of in utero exposure to a 2450 MHz Wi-Fi signal (2 hr/day, 6 days/week for 18 days) on pregnant rats and their pups. Three levels in terms of whole-body specific absorption rate were used: 0.08, 0.4, and 4 W/kg. The prenatal study on fetuses delivered by caesarean (P20) concerned five females/group. The dams and their offspring were observed for 28 days after delivery (15 females/group). RESULTS: For all test conditions, no abnormalities were noted in the pregnant rats and no significant signs of toxicity were observed in the pre- and postnatal development of the pups, even at the highest level of 4 W/kg. CONCLUSIONS: In the present study, no teratogenic effect of repeated exposures to the Wi-Fi wireless communication signal was demonstrated even at the highest level of 4 W/kg. The results from this screening study aimed at investigating Wi-Fi effects, strengthen the previous conclusions that teratology and development studies have not detected any noxious effects of exposures to mobile telephony-related RF fields at exposure levels below standard limits. PMID- 22311619 TI - Photochemical disruption of polyelectrolyte multilayers. AB - Photoreactive polyelectrolyte multilayers (PEMs) that dissolve upon UV irradiation are described. Light-induced switching of the formal charge of a photoreactive polycation resulted in repulsive interlayer electrostatic forces, and caused the dissolution of PEM films. Combining both photoreactive and inert polycations in the same film yielded additional control over the light-induced change in film thickness. PMID- 22311620 TI - Safe and effective methylphenidate therapy in a pediatric patient with glaucoma. AB - Stimulant medications used as first-line treatment in attention deficit hyperactivity disorder (ADHD) are contraindicated in patients with glaucoma. We present the first reported case of using methylphenidate therapy to safely and effectively treat ADHD in a pediatric patient with glaucoma. PMID- 22311621 TI - Deterioration of cutaneous microcirculatory status of Kawasaki disease. AB - Kawasaki disease (KD) is associated with generalized vasculitis with a predilection for coronary artery leading to ectasia and aneurysm in some cases. The aim of this study was to noninvasively assess the cutaneous microcirculation and correlate it with the coronary artery diameter in these patients. Laser Doppler flowmetry and dynamic capillaroscopy were performed at the nailbeds to assess total cutaneous blood flow and microcirculation in children with KD, both in the afebrile phase (after the resolution of fever) and convalescent phases, in comparison to controls. The 100 subjects analyzed in this study included 64 patients with KD (33 in afebrile phase and 31 in convalescent phase) and 36 normal controls. In KD, the capillary morphology was abnormal when compared to controls, with a larger diameter of the arterial and venous limbs, a higher intercapillary distance and a decrease in the loop numbers. Significantly decreased capillary blood cell velocity was noted in afebrile phase but not in convalescent phase. In the afebrile phase, a decreased capillary blood cell velocity significantly correlated with an increased coronary artery diameter. In conclusion, KD patients, both in the afebrile and convalescent phases, exhibited morphologic alterations in the microcirculation when compared to the controls. The results indicate the potential role of dynamic capillaroscopy for the noninvasive survey of microcirculation abnormalities in patients with KD. PMID- 22311622 TI - Molecular recognition of hydrocarbon guests by a supramolecular capsule formed by the 4:4 self-assembly of tris(Zn(2+)-cyclen) and trithiocyanurate in aqueous solution. AB - We have previously reported that the trimeric Zn(2+)-cyclen complex (tris(Zn(2+) cyclen), [Zn(3)L(1)](6+)) and the trianion of trithiocyanuric acid (TCA(3-)) assembled in a 4:4 ratio to form a cuboctahedral supramolecular cage, [(Zn(3)L(1))(4)(TCA(3-))(4)](12+) (hereafter referred to as a Zn-cage), in neutral aqueous solution (cyclen=1,4,7,10-tetraazacyclododecane). Herein, we examined the molecular recognition of C(1)-C(12) hydrocarbons (C(n)H((2n+2)) (n~1 12)), cyclopentane, cyclododecane, cis-decalin, and trans-decalin by the Zn-cage under normal atmospheric pressure. This cage complex was also able to encapsulate guest molecules that had larger volumes than that of the inner cavity of the Zn cage, thereby suggesting that the inner shape of the Zn-cage was flexible. Computational simulations of Zn-cage-guest complexes provided support for this conclusion. Moreover, the solvent-accessible surface areas (SASA) of the Zn-cage host, guest molecules, and the Zn-cage-guest complexes were calculated and the data were used to explain the order of stability determined by the guest replacement experiments. The storage of volatile molecules in aqueous solution by the Zn-cage is also discussed. PMID- 22311623 TI - Influencing the symmetry of high-nuclearity and high-spin manganese oxo clusters: supramolecular approaches to manganese-based keplerates and chiral solids. PMID- 22311624 TI - The anthropology of psychopharmacology: commentary on contributions to the analysis of pharmaceutical self and imaginary. PMID- 22311625 TI - Simultaneous determination of lactate and pyruvate in human sweat using reversed phase high-performance liquid chromatography: a noninvasive approach. AB - The simultaneous determination of lactate and pyruvate in sweat has been performed using reversed phase high-performance liquid chromatography (RP-HPLC) with UV detection at 220 nm. The calibration curves were linear in the investigated range 0.3 - 350 mm of lactate, 0.003- 1 mm of pyruvate. The sensitivity was good with a limit of detection of 0.03 mm for lactate and 0.001 mm for pyruvate. Recoveries evaluated for the entire procedure were 102 +/- 0.1 and 96 +/- 0.1 for lactate and pyruvate, respectively. The method was successfully applied to analysis of sweat in 8 athletes at rest (pilocarpine sweating) and during physical exercise. PMID- 22311627 TI - Spotlight on respiratory viruses 2012: introduction. PMID- 22311626 TI - Preventive effects of hyperbaric oxygen treatment on glycerol-induced myoglobinuric acute renal failure in rats. AB - Myoglobinuric acute renal failure (ARF) is a uremic syndrome caused by traumatic or non-traumatic skeletal muscle breakdown and intracellular elements that are released into the bloodstream. We hypothesized that hyperbaric oxygen (HBO) therapy could be beneficial in the treatment of myoglobinuric ARF caused by rhabdomyolysis. A total of 32 rats were used in the study. The rats were divided into four groups: control, control+hyperbaric oxygen (control+HBO), ARF, and ARF+hyperbaric oxygen (ARF+HBO). Glycerol (8 ml/kg) was injected into the hind legs of each of the rats in ARF and ARF+HBO groups. 2.5 atmospheric absolute HBO was applied to the rats in the control+HBO and ARF+HBO groups for 90 min on two consecutive days. Plasma urea, creatinine, sodium, potassium, calcium, aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase, creatinine kinase and urine creatinine and sodium were examined. Creatinine clearance and fractional sodium excretion could then be calculated. Superoxide dismutase, catalase, glutathione and malondialdehyde (MDA) levels were assessed in renal tissue. Tissue samples were evaluated by Hematoxylin-eosin, PCNA and TUNEL staining histopathologically. MDA levels were found to be significantly decreased whereas SOD and CAT were twofold higher in the ARF+HBO group compared to the ARF group. Renal function tests were ameliorated by HBO therapy. Semiquantitative evaluation of histopathological findings indicated that necrosis and cast formation was decreased by HBO therapy and TUNEL staining showed that apoptosis was inhibited. PCNA staining showed that HBO therapy did not increase regeneration. Ultimately, we conclude that, in accordance with our hypothesis, HBO could be beneficial in the treatment of myoglobinuric ARF. PMID- 22311628 TI - A survey of the clinical course and management of Japanese patients deficient in natural anticoagulants. AB - Few data are available on the clinical course of Japanese patients deficient in natural anticoagulants (antithrombin (AT), protein C, and protein S). We conducted a nationwide survey to reveal the clinical course of these patients. Questionnaires were sent to 321 council members of the Japanese Society on Thrombosis and Hemostasis, Japanese Society for Vascular Surgery, and Japanese Society of Phlebology. A total of 103 responses were obtained and data of 183 patients were collected. Of 183 patients, 142 (78%) experienced at least one episode of venous thromboembolism (VTE). The first VTE occurred before the age of 40 years in 71 patients (45%). Venous thromboembolism recurred in 15 (39%) patients with AT deficiency and 19 (18%) patients with other deficiencies. These findings suggest that half of the first episodes of VTE in patients deficient in natural anticoagulants occur before middle age and the risk of VTE recurrence is high in patients with AT deficiency. PMID- 22311629 TI - Description of response to aspirin and clopidogrel in outpatients with coronary artery disease using multiple electrode impedance aggregometry. AB - Identification of outpatients with high platelet reactivity (HPR) on antiplatelet treatment is an unmet need. The present study was conducted in healthy individuals (n = 50) and in outpatients with coronary artery disease (CAD) at a distance from the acute ischemic episode (aspirin group, n = 71; aspirin/clopidogrel group, n = 106). We studied the feasibility and the precision of whole blood multiple electrode aggregometry (MEA) after triggering platelet aggregation by arachidonic acid or adenosine diphospate (ADP). The MEA can be performed on whole blood within 2 hours after sample venipuncture. The threshold for the diagnosis of HPR is situated at 55 and 50 U for the arachidonic acid and ADP test, respectively. Frequency of HPR was 7% and 20% in aspirin and aspirin/clopidogrel groups, respectively. In 3.8% of patients in aspirin/clopidogrel group, combined HPR on aspirin and clopidogrel was found. In outpatients with CAD, use of MEA is feasible for the diagnosis of HPR. PMID- 22311630 TI - Interactions of oversulfated chondroitin sulfate (OSCS) from different sources with unfractionated heparin. AB - In 2008, oversulfated chondroitin sulfate (OSCS) was identified as the main contaminant in recalled heparin. Oversulfated chondroitin sulfate can be prepared from bovine (B), porcine (P), shark (Sh), or skate (S) origin and may produce changes in the antithrombotic, bleeding, and hemodynamic profile of heparins. This study examines the interactions of various OSCSs on heparin in animal models of thrombosis and bleeding, as well as on the anticoagulant and antiprotease effects in in vitro assays. Mixtures of 70% unfractionated heparin (UFH) with 30% OSCS from different sources were tested. In the in vitro activated partial thromboplastin time (aPTT) assay, all contaminant mixtures showed a decrease in clotting times. In addition, a significant increase in bleeding time compared to the control (UFH/saline) was observed. In the thrombosis model, no significant differences were observed. The OSCSs significantly increased anti-Xa activity in ex vivo blood samples. These results indicate that various sources of OSCS affect the hemostatic properties of heparin. PMID- 22311631 TI - Assessment of levels of vascular endothelial growth factor in patients with ESRD and its possible role in cardiovascular morbidity and mortality. AB - Patients with end-stage renal disease (ESRD) are known to have an elevation of a variety of abnormal thrombotic and inflammatory markers associated with high cardiovascular mortality. Vascular endothelial growth factor (VEGF) is also dysregulated in ESRD but not much is known about the serum levels of VEGF in patients with ESRD. Published reports suggest that elevated levels of VEGF may be protective to the kidney during periods of acute injury and may maintain local glomerular function. Impaired production of VEGF may lead to proteinuria, hypertension, and thrombotic microangiopathy. However, its role in chronic kidney disease or ESRD remains undefined. In our study, we analyzed blood samples of 52 patients with ESRD on stable hemodialysis regimen and measured predialysis serum levels of VEGF and compared these with blood samples obtained from 50 healthy volunteers in order to study differences between baseline levels of VEGF and also attempted to determine its role in ESRD-related cardiovascular mortality. PMID- 22311632 TI - Impaired endothelial-dependent and endothelium-independent vasodilatation in patients with thromboangiitis obliterans. AB - BACKGROUND: Endothelial dysfunction is the key process in the development of atherosclerosis. The aim of our study was to evaluate endothelial dysfunction measured by the noninvasive technique of Celermajer that plays a role in the pathogenesis of thrombangitis obliterans. METHODS: A total of 36 patients with thrombangitiis obliterans ([TAO]; mean age 44.9 +/- 1.3 years) were compared with 30 healthy individuals (mean age 36.1 +/- 1.8 years). High frequency ultrasound was used to measure changes in response to reactive hyperemia (leading to flow mediated endothelium-dependent dilatation) and in response to 0.4 mg sublingual nitroglycerin ([NTG]; leading to NTG-induced, endothelium-independent dilatation). RESULTS: Patients with TAO showed a lower but statistically not significant flow-mediated dilatation and a statistically significant reduced NTG induced vasodilatation than the control group. CONCLUSION: Our results suggest that both mechanisms play a role in patients with TAO, the endothelium independent impaired vasodilatation even in a more significant way than the impaired endothelium-dependent vasodilatation. PMID- 22311633 TI - Deep vein thrombosis, tranexamic acid, and a negative d-dimer. PMID- 22311634 TI - A randomized controlled trial on the hemostasis of femoral artery using topical hemostatic agent. AB - OBJECTIVE: Evaluation of the effect of using a topical hemostatic agent named "ChitoHem((r))" on different factors on patients undergoing diagnostic coronary angiography. METHODS: The present blind, randomized, controlled study included 124 patients randomly divided into 2 groups. In the treatment group following femoral sheath removal, ChitoHem((r)) powder and in the control group conventional hemostatic procedure was applied. RESULTS: In the treatment group, time to hemostasis, ambulation, and the use of sandbag were significantly shorter compared with the control group, respectively (4.6 +/- 1.3 vs 12.4 +/- 4.4 minutes, 3.5 +/- 2.7 vs 23.0 +/- 1.73 hours and 1.6 vs 98.4%; P < .05). There were no significant differences in hematoma formation and re-bleeding between the 2 groups. CONCLUSION: It was exhibited ChitoHem((r)) topical hemostatic powder used on treatment patients undergoing diagnostic coronary angiography was statistically superior at reducing the time to hemostasis and ambulation as well as the use of sandbags compared with manual compression in control group. PMID- 22311635 TI - Developmentally regulated expression of MEF2C limits the response to BCR engagement in transitional B cells. AB - Transitional and naive mature peripheral B cells respond very differently to B cell receptor (BCR) cross-linking. While transitional B cells undergo apoptosis upon BCR engagement, mature B cells survive and proliferate. This differential response correlates with the capacity of mature, but not transitional B cells to transcribe genes that promote cell survival and proliferation, including those encoding c-Myc and the Bcl-2 family members Bcl-xL and A1. We recently demonstrated that transitional B cells fail to assemble transcriptional machinery at the promoter region of these target genes despite equivalent cytoplasmic signaling and nuclear translocation of key transcription factors including NF kappaB and nuclear factor of activated T cells (NFAT). The transcription factor myocyte enhancer factor-2C (MEF2C) is regulated by both calcineurin and mitogen activated protein kinase signaling pathways, and is essential for proliferation and survival downstream of BCR engagement in mature B cells. In this work, we demonstrate that transitional B cells have intrinsically low levels of MEF2C protein and DNA-binding activity, and that this developmental difference in MEF2C expression is functionally significant. Forced expression of MEF2C in transitional B cells promoted cell survival, proliferation, and upregulation of pro-survival genes. Thus, low MEF2C expression limits transitional B-cell responsiveness to BCR engagement before these cells reach maturity. PMID- 22311636 TI - Advancing cell biology through proteomics in space and time (PROSPECTS). AB - The term "proteomics" encompasses the large-scale detection and analysis of proteins and their post-translational modifications. Driven by major improvements in mass spectrometric instrumentation, methodology, and data analysis, the proteomics field has burgeoned in recent years. It now provides a range of sensitive and quantitative approaches for measuring protein structures and dynamics that promise to revolutionize our understanding of cell biology and molecular mechanisms in both human cells and model organisms. The Proteomics Specification in Time and Space (PROSPECTS) Network is a unique EU-funded project that brings together leading European research groups, spanning from instrumentation to biomedicine, in a collaborative five year initiative to develop new methods and applications for the functional analysis of cellular proteins. This special issue of Molecular and Cellular Proteomics presents 16 research papers reporting major recent progress by the PROSPECTS groups, including improvements to the resolution and sensitivity of the Orbitrap family of mass spectrometers, systematic detection of proteins using highly characterized antibody collections, and new methods for absolute as well as relative quantification of protein levels. Manuscripts in this issue exemplify approaches for performing quantitative measurements of cell proteomes and for studying their dynamic responses to perturbation, both during normal cellular responses and in disease mechanisms. Here we present a perspective on how the proteomics field is moving beyond simply identifying proteins with high sensitivity toward providing a powerful and versatile set of assay systems for characterizing proteome dynamics and thereby creating a new "third generation" proteomics strategy that offers an indispensible tool for cell biology and molecular medicine. PMID- 22311637 TI - Identification of autophagosome-associated proteins and regulators by quantitative proteomic analysis and genetic screens. AB - Autophagy is one of the major intracellular catabolic pathways, but little is known about the composition of autophagosomes. To study the associated proteins, we isolated autophagosomes from human breast cancer cells using two different biochemical methods and three stimulus types: amino acid deprivation or rapamycin or concanamycin A treatment. The autophagosome-associated proteins were dependent on stimulus, but a core set of proteins was stimulus-independent. Remarkably, proteasomal proteins were abundant among the stimulus-independent common autophagosome-associated proteins, and the activation of autophagy significantly decreased the cellular proteasome level and activity supporting interplay between the two degradation pathways. A screen of yeast strains defective in the orthologs of the human genes encoding for a common set of autophagosome associated proteins revealed several regulators of autophagy, including subunits of the retromer complex. The combined spatiotemporal proteomic and genetic data sets presented here provide a basis for further characterization of autophagosome biogenesis and cargo selection. PMID- 22311639 TI - InCl3-driven regioselective synthesis of functionalized/annulated quinolines: scope and limitations. AB - The efficient, regioselective synthesis of functionalized/annulated quinolines was achieved by the coupling of 2-aminoaryl ketones with alkynes/active methylenes/alpha-oxoketene dithioacetals promoted by InCl(3) in refluxing acetonitrile as well as under solvent-free conditions in excellent yields. This transformation presumably proceeded through the hydroamination-hydroarylation of alkynes, and the Friedlander annulation of active methylene compounds and alpha oxoketene dithioacetals with 2-aminoarylketones. In addition, simple reductive and oxidative cyclization of 2-nitrobenzaldehyde and 2-aminobenzylalcohol, respectively, afforded substituted quinolines. Systematic optimization of the reaction parameters allowed us to identify two-component coupling (2CC) conditions that were tolerant of a wide range of functional groups, thereby providing densely functionalized/annulated quinolines. This approach tolerates the synthesis of various bioactive quinoline frameworks from the same 2 aminoarylketones under mild conditions, thus making this strategy highly useful in diversity-oriented synthesis (DOS). The scope and limitations of the alkyne-, activated methylene-, and alpha-oxoketene dithioacetal components on the reaction were also investigated. PMID- 22311638 TI - Candidate hippocampal biomarkers of susceptibility and resilience to stress in a rat model of depression. AB - Susceptibility to stress plays a crucial role in the development of psychiatric disorders such as unipolar depression and post-traumatic stress disorder. In the present study the chronic mild stress rat model of depression was used to reveal stress-susceptible and stress-resilient rats. Large-scale proteomics was used to map hippocampal protein alterations in different stress states. Membrane proteins were successfully captured by two-phase separation and peptide based proteomics. Using iTRAQ labeling coupled with mass spectrometry, more than 2000 proteins were quantified and 73 proteins were found to be differentially expressed. Stress susceptibility was associated with increased expression of a sodium-channel protein (SCN9A) currently investigated as a potential antidepressant target. Differential protein profiling also indicated stress susceptibility to be associated with deficits in synaptic vesicle release involving SNCA, SYN-1, and AP-3. Our results indicate that increased oxidative phosphorylation (COX5A, NDUFB7, NDUFS8, COX5B, and UQCRB) within the hippocampal CA regions is part of a stress-protection mechanism. PMID- 22311640 TI - Event-related potentials to changes of rhythmic unit: differences between musicians and nonmusicians. AB - We investigated whether the expected differences between musicians and nonmusicians in their ability to detect a rhythm change were reflected in their event-related potentials (ERPs) and, if reflected, how these ERP differences associated with behavioral indices. Stimuli were three consecutive and equally spaced drum beats followed by a rest period to form a rhythmic unit (RU). By using three different inter-beat periods, three RUs were produced. Combinations of these RUs served as the "target/standard" pairs of an oddball sequence. In four different experiments, we tried two RU-change types each with two levels of detection difficulty. ERPs were recorded from the F3, Fz, F4, Cz and Pz scalp sites of 12 musicians and 12 nonmusicians. RT, hit and false-alarm rates were also measured. The data have shown with high statistical confidence that, associated with the musicians' better detection performance and shorter RTs, their ERP P3 to rhythm changes peaked significantly earlier and was significantly larger compared to nonmusicians. Intergroup ERP differences allowed above 90% correct classification. This study has also showed that not only violations of relatively complex musical regularities, but very simple rhythmic unit alterations could lead to significant P3 differences between musicians and nonmusicians. The high accuracy of the musician/nonmusician classification based only on their P3 data strongly supported the hypothesis that sensory and/or cognitive advantage of musicians in detecting rhythm changes does reflect in their P3. PMID- 22311641 TI - Minimally invasive procedures reduce perihematomal endothelin-1 levels and the permeability of the BBB in a rabbit model of intracerebral hematoma. AB - To observe the effects of minimally invasive procedures for the evacuation of intracerebral hematomas on perihematomal ET-1 expression and their correlation with blood-brain barrier (BBB) permeability. Forty-five rabbits (2.8-3.4 kg body weight) were randomly divided into a normal control group (NC group, 15 rabbits), a model control group (MC group, 15 rabbits) and a minimally invasive group (MI group, 15 rabbits). A model of intracerebral hemorrhage (ICH) was prepared in the MC and MI groups by infusing autologous arterial blood into the rabbits' brains; the same procedure was also performed in the NC group but without infusing blood into the rabbits' brains. The intracerebral hematomas were evacuated by a stereotactic procedure in the minimally invasive group 6 h after the model was established. The neurological functions, ET-1 expression and the perihematomal BBB permeability were determined and analyzed in all of the animals. The number of endothelial cells with ET-1-positive expression and the perihematomal BBB permeability significantly increased 1, 3, and 7 days after the ICH model was prepared successfully, as compared to the NC group. In the MI group, however, both measurements decreased markedly compared with the MC group at the same time point. A positive correlation between the number of endothelial cells with ET-1 positive expression and BBB permeability was observed. Increased BBB permeability might be associated with perihematomal ET-1 levels. Minimally invasive procedures for the evacuation of intracerebral hematomas could significantly decrease BBB permeability in perihematomal brain tissues, likely by reducing the production of ET-1. PMID- 22311642 TI - Occipital neuralgia: a symptomatic case caused by an abnormal left vertebral artery. PMID- 22311643 TI - Combustion synthesis and electrochemical properties of the small hydrofullerene C50H10. AB - The hydrofullerene C(50)H(10) is synthesized by low-pressure benzene-oxygen diffusion combustion. The structure of C(50)H(10) is identified through NMR, mass spectrometry, and IR and Raman spectroscopy as a D(5h) symmetric closed-cage molecule with five pairs of fused pentagons stabilized by ten hydrogen atoms. UV/Vis and fluorescence spectrometric analyses disclose its optical properties as comparable with those of its chloride cousin (C(50)Cl(10)). Cyclic and square wave voltammograms reveal that the first reduction potential of C(50)H(10) is more negative than that of C(50)Cl(10) as well as C(60), with implications for the utilization of C(50)H(10) as a promising electron acceptor for photovoltaic applications. PMID- 22311644 TI - A comparative study of hydrolysis and transglycosylation activities of fungal beta-glucosidases. AB - beta-glucosidases (BGs) from Aspergillus fumigatus, Aspergillus niger, Aspergillus oryzae, Magnaporthe grisea, Neurospora crassa, and Penicillium brasilianum were purified to homogeneity, and investigated for their (simultaneous) hydrolytic and transglycosylation activity in samples with high concentrations of either cellobiose or glucose. The rate of the hydrolytic process (which converts one cellobiose to two glucose molecules) shows a maximum around 10-15 mM cellobiose and decreases with further increase in the concentration of substrate. At the highest investigated concentration (100 mM cellobiose), the hydrolytic activity for the different enzymes ranged from 10% to 55% of the maximum value. This decline in hydrolysis was essentially compensated by increased transglycosylation (which converts two cellobiose to one glucose and one trisaccharide). Hence, it was concluded that the hydrolytic slowdown at high substrate concentrations solely relies on an increased flow through the transglycosylation pathway and not an inhibition that delays the catalytic cycle. Transglycosylation was also detected at high product (glucose) concentrations, but in this case, it was not a major cause for the slowdown in hydrolysis. The experimental data was modeled to obtain kinetic parameters for both hydrolysis and transglycosylation. These parameters were subsequently used in calculations that quantified the negative effects on BG activity of respectively transglycosylation and product inhibition. The kinetic parameters and the mathematical method presented here allow estimation of these effects, and we suggest that this may be useful for the evaluation of BGs for industrial use. PMID- 22311646 TI - Improvement of tolerance of Saccharomyces cerevisiae to hot-compressed water treated cellulose by expression of ADH1. AB - Hot-compressed water treatment of cellulose and hemicellulose for subsequent bioethanol production is a novel, economically feasible, and nonhazardous method for recovering sugars. However, the hot-compressed water-treated cellulose and hemicellulose inhibit subsequent ethanol fermentation by the yeast Saccharomyces cerevisiae. To overcome this problem, we engineered a yeast strain with improved tolerance to hot-compressed water-treated cellulose. We first determined that glycolaldehyde has a greater inhibitory effect than 5-HMF and furfural and a combinational effect with them. On the basis of the hypothesis that the reduction of glycolaldehyde to ethylene glycol should detoxify glycolaldehyde, we developed a strain overexpressing the alcohol dehydrogenase gene ADH1. The ADH1 overexpressing strain exhibits an improved fermentation profile in a glycolaldehyde-containing medium. The conversion ratio of glycolaldehyde to ethylene glycol is 30 +/- 1.9% when the control strain is used; this ratio increases to 77 +/- 3.6% in the case of the ADH1-overexpressing strain. A glycolaldehyde treatment and the overexpression of ADH1 cause changes in the fermentation products so as to balance the metabolic carbon flux and the redox status. Finally, the ADH1-overexpressing strain shows a statistically significantly improved fermentation profile in a hot-compressed water-treated cellulose-containing medium. The conversion ratio of glycolaldehyde to ethylene glycol is 33 +/- 0.85% when the control strain is used but increases to 72 +/- 1.7% in the case of the ADH1-overexpressing strain. These results show that the reduction of glycolaldehyde to ethylene glycol is a promising strategy to decrease the toxicity of hot-compressed water-treated cellulose. This is the first report on the improvement of yeast tolerance to hot-compressed water treated cellulose and glycolaldehyde. PMID- 22311647 TI - Comparison of alkyl hydroperoxide reductase and two water-forming NADH oxidases from Bacillus cereus ATCC 14579. AB - Bacillus cereus (B. cereus) is an ubiquitous facultative anaerobic bacterium, and its growth in aerobic environment correlates to the functions of its oxygen defense system. Water-forming NADH oxidase (nox-2) can catalyze the conversion of oxygen to water with concomitant NADH oxidation in anaerobic microorganisms. Here, we report the cloning and characterization of two annotated nox-2 s (nox 2(444) and nox-2(554)) from B. cereus ATCC 14579 and their comparison with another oxidative stress defense system alkyl hydroperoxide reductase (AhpR) from this microbe, which composed of two enzymes-hydrogen peroxide-forming NADH oxidase (nox-1) and peroxidase. Both nox-2 and AhpR catalyze the same reaction in the presence of oxygen. With the stimulation of exogenously added FAD, the maximum activity of nox-1, nox-2(444), and nox-2(554) could reach 27.7 U/mg, 22.9 U/mg, and 2.4 U/mg, respectively, at pH 7.0, 30 degrees C. Different from nox-1, both nox-2 s were thermotolerant enzymes and could maintain above 87% of their optimum activity at 80 degrees C, which was not found in other nox-2 s. As for operational stability, all are turnover-limited. Exogenously added reductive reagent dithiothreitol could dramatically increase the total turnover number of nox-2(444) and nox-2(554) by twofold and threefold, respectively, but had no effect on AhpR or nox-1. PMID- 22311648 TI - Available methods for assembling expression cassettes for synthetic biology. AB - Studies in the structural biology of the multicomponent protein complex, metabolic engineering, and synthetic biology frequently rely on the efficient over-expression of these subunits or enzymes in the same cell. As a first step, constructing the multiple expression cassettes will be a complicated and time consuming job if the classic and conventional digestion and ligation based cloning method is used. Some more efficient methods have been developed, including (1) the employment of a multiple compatible plasmid expression system, (2) the rare-cutter-based design of vectors, (3) in vitro recombination (sequence and ligation independent cloning, the isothermally enzymatic assembly of DNA molecules in a single reaction), and (4) in vivo recombination using recombination-efficient yeast (in vivo assembly of overlapping fragments, reiterative recombination for the chromosome integration of foreign expression cassettes). In this review, we systematically introduce these available methods. PMID- 22311649 TI - Tissue distribution of anidulafungin in neonatal rats. AB - Anidulafungin, an echinocandin, is currently approved for treatment of fungal infections in adults. There is a high unmet medical need for treatment of fungal infections in neonatal patients, who may be at higher risk of infections involving bone, brain, and heart tissues. This in vivo preclinical study investigated anidulafungin distribution in plasma, bone, brain, and heart tissues in neonatal rats. Postnatal day (PND) 4 and PND 8 Fischer (F344/DuCrl) rats were dosed subcutaneously once with anidulafungin (10 mg/kg) or once daily for 5 days (PND 4-8). Plasma and tissue samples were collected and anidulafungin levels were measured by liquid chromatography-tandem mass spectrometry. The mean plasma Cmax and AUC0-24 values were consistent with single-dose plasma pharmacokinetics (dose normalized) reported previously for adult rats. Observed bone concentrations were similar to plasma concentrations regardless of dosing duration, with bone-to plasma concentration ratios of approximately 1.0. Heart concentrations were higher than plasma, with heart to plasma concentration ratios of 1.3- to 1.8 fold. Brain concentrations were low after single dose, with brain-to-plasma concentration ratio of approximately 0.23, but increased to approximately 0.71 after 5 days of dosing. Tissue concentrations were nearly identical after single dose administration in both PND 4 and PND 8 animals, indicating that anidulafungin does not appear to differentially distribute in this period in neonatal rats. In conclusion, anidulafungin distributes to bone, brain, and heart tissues of neonatal rats; such results are supportive of further investigation of efficacy against infections involving bone, brain, and heart tissues. PMID- 22311650 TI - Formation of a germylyne complex: dehydrogenation of a hydrido(hydrogermylene)tungsten complex with mesityl isocyanate. PMID- 22311651 TI - Validation and application of a liquid chromatography-tandem mass spectrometric method for the determination of GDC-0834 and its metabolite in human plasma using semi-automated 96-well protein precipitation. AB - A liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of GDC-0834 and its amide hydrolysis metabolite (M1) in human plasma to support clinical development. The method consisted of semi-automated 96-well protein precipitation extraction for sample preparation and LC-MS/MS analysis in positive ion mode using TurboIonSpray(r) for analysis. D6-GDC-0834 and D6-M1 metabolite were used as internal standards. A linear regression (weighted 1/concentration(2) ) was used to fit calibration curves over the concentration range of 1 - 500 ng/mL for both GDC-0834 and M1 metabolite. The accuracy (percentage bias) at the lower limit of quantitation (LLOQ) was 5.20 and 0.100% for GDC-0834 and M1 metabolite, respectively. The precision (CV) for samples at the LLOQ was 3.13-8.84 and 5.20 8.93% for GDC-0834 and M1 metabolite, respectively. For quality control samples at 3, 200 and 400 ng/mL, the between-run CV was <= 7.38% for GDC-0834 and <= 8.20% for M1 metabolite. Between run percentage bias ranged from -2.76 to 6.98% for GDC-0834 and from -6.73 to 2.21% for M1 metabolite. GDC-0834 and M1 metabolite were stable in human plasma for 31 days at -20 and -70 degrees C. This method was successfully applied to support a GDC-0834 human pharmacokinetic-based study. PMID- 22311652 TI - Aldosterone in heart disease. AB - Numerous studies have now shown that sustained elevation of aldosterone levels induces cardiovascular damage independent from its effects on regulation of renal sodium and blood pressure. Increased aldosterone and cortisol levels in patients with heart failure independently predict the risk of mortality. Over the past decade, there has been increased interest in identifying the role of the receptor for aldosterone, the mineralocorticoid receptor (MR), following the results from the large clinical heart failure trials that showed low doses of MR antagonists reduced morbidity and mortality in heart failure and myocardial infarction, even though plasma levels of aldosterone were in the physiologic range. The mechanism for this cardioprotective action remains to be defined, although changes in the redox state have been shown to play a key role in MR-mediated cardiac damage. This review will highlight some of these studies and provide an update on the action of aldosterone in heart disease. PMID- 22311653 TI - Development of integrative bioethics in the Mediterranean area of South-East Europe. AB - With regards to its origin, foundation and development, bioethics is a relatively new discipline, scientific and theoretical field, where different and even contradicting definition models and methodological patterns of its formation and application meet. In some philosophical orientations, bioethics is considered to be a sub-discipline of applied ethics as a traditional philosophical discipline. Yet in biomedical and other sciences, bioethics is designated as a specialist scientific discipline, or a sort of a new medical ethics. The concept of integrative bioethics as an interdisciplinary scholarly and pluriperspectivistic area goes beyond such one-sided determinations, both philosophical and scientistic, and intends to integrate the philosophical approach to bioethics with its particular scientific contents, as well as different cultural dimensions and perspectives. This concept of integrative bioethics has gradually developed at philosophical and interdisciplinary conferences and institutions on the "bioethical islands" of the Croatian Mediterranean. In this paper, the author follows the formation, development and prospects of integrative bioethics in the wider region of the Mediterranean and Southeast Europe. PMID- 22311654 TI - The promise, pitfalls and progress of RNA-interference-based antiviral therapy for respiratory viruses. AB - Advances in the understanding of RNA biological processing and control are leading to new concepts in human therapeutics with practical implications for many human diseases, including antiviral therapy of respiratory viruses. So called 'non-coding RNA' exerts specific and profound functional control on regulation of protein production and indeed controls the expression of all genes through processes collectively known as RNA interference (RNAi). RNAi is a naturally occurring intracellular process that regulates gene expression through the silencing of specific messenger RNAs (mRNAs). Methods are being developed that allow the catalytic degradation of targeted mRNAs using specifically designed complementary small interfering RNAs (siRNA). siRNAs are now being chemically modified and packaged into advanced delivery systems so as to acquire drug-like properties and the ability to deliver their effects systemically. Recent in vivo studies have provided proofs of the concept that RNAi may be useful therapeutically. Much of the design of these siRNAs can be accomplished bioinformatically, thus potentially expediting drug discovery and opening new avenues of therapy for many uncommon, orphan, or emerging diseases. Theoretically, any disease that can be ameliorated through knockdown of any endogenous or exogenous protein is a potential therapeutic target for RNAi-based therapeutics. Lung diseases in general are attractive targets for RNAi therapeutics, since the location of affected cells increases their accessibility to topical administration of siRNA, and respiratory viral infections are particularly attractive targets for RNAi-based drug discovery and development. RNAi therapeutics have been shown to exert potent antiviral effects against respiratory syncytial virus (RSV), parainfluenza, influenza, coronaviruses, measles and human metapneumoviruses in vitro and in vivo. Recently, a double blind placebo-controlled clinical trial of an RNAi-based therapeutic against RSV demonstrated that this technology has therapeutic activity, representing the first proof-of-concept test of efficacy for RNAi's therapeutic effect in humans. This review discusses the science behind RNAi and the potential practical issues in applying this technology to various respiratory viral diseases. PMID- 22311655 TI - Resorcinarene bis-thiacrowns: prospective host molecules for silver encapsulation. AB - Mixed-donor atom tetramethoxy resorcinarene bis-thiacrown hosts, in which the crown unit contains both hard oxygen and soft sulfur donor atoms, were synthesized for soft metal cation binding. The binding properties were investigated both in solution and in the solid state by NMR spectroscopy and X ray crystallography. It was found that the resorcinarene bis-thiacrowns were able to complex silver cations with remarkable affinity forming readily 1:2 host-guest complexes in solution. The solid state structures also revealed that the bis thiacrowns form silver complexes in an unanticipated endo- and exo-cavity fashion within the same host molecule. Both the solution and solid state studies indicated the sulfur atoms to be the major contributing donor atoms in forming the binding interactions with silver cations. PMID- 22311657 TI - Radiological dorsal tilt analysis of AO type A, B, and C fractures of the distal radius treated conservatively or with extra-focal K-wire plus external fixateur. AB - OBJECTIVE: Fractures of the distal radius are amongst the most common injury patterns. The dorsal tilt represents an important co-factor determining functional outcome. The purpose of this study was to analyze the radiological dorsal tilt and identify critical time frames in conservative and operative treatment of distal radius fractures. MATERIALS AND METHODS: Eighty-seven conservatively treated (hematoma block assisted reduction and splinting) and 37 operatively treated (reduction, extra-focal K-wire fixation, bridging external fixateur) AO type A, B, and C fractures of the distal radius in 124 females were retrospectively analyzed. The dorsal tilt at the initial, post-reduction, and 2 weeks post-reduction stages was correlated with the final radiographic outcome at 6 weeks. RESULTS: Mean initial dorsal tilt was 16.53 degrees in the conservatively treated group and 26.76 degrees in the operatively treated group. Mean dorsal tilt after 6 weeks showed significant differences from the mean initial dorsal tilt at time of presentation within both groups (both groups p < 0.000). No significant differences between the two groups were found after 6 weeks of treatment (p = 0.194) regardless of the underlying AO fracture type. Conservatively treated radius fractures showed a significantly higher slip rate within the first 2 weeks (primary slip rate), whereas the operative group presented a significantly higher slip rate between the 2-week and 6-week radiographic checks (secondary slip rate). CONCLUSION: In terms of dorsal tilt, conservative (cast immobilization) and operative (K-wire fixation plus external fixateur) treatment demonstrated no significant differences at the final radiographic examination (6 weeks) regardless of the underlying AO fracture type. Both treatment groups showed treatment-associated different primary and secondary slip rates, indicating a need for more frequent radiographic checks within these critical time frames. PMID- 22311658 TI - Central low-grade osteosarcoma: a diagnostic challenge. PMID- 22311659 TI - A histological evaluation of a low-level laser therapy as an adjunct to periodontal therapy in patients with diabetes mellitus. AB - Diabetes mellitus (DM) and chronic periodontitis are common chronic diseases in adults in the world population. DM has a strong influence on the oral cavity and represents a risk factor for gingivitis and periodontitis. Low-level laser therapy (LLLT) has proven effective in the reduction of inflammation and swelling. The aim of the present study was to evaluate the efficacy of LLLT in diabetic periodontitis through histological analysis. A total of 300 diabetics with chronic periodontal disease and teeth indicated for extraction were assigned into six equal groups. In the groups 1 and 4, indicated teeth were extracted before treatment, and in the rest of the groups upon completion of the entire treatment. All patients received oral hygiene instructions and full-mouth conservative periodontal treatment. In groups 3 and 6, LLLT was applied (670 nm, 5 mW, 2 J/cm(2), 16 min, 5 days). Histologic findings of gingival tissue treated with LLLT showed expressed healing, as is evident by the absence of inflammatory cells. Tissue edema could not be seen, and the number of blood vessels was reduced. In the gingival lamina, propria pronounced collagenization and homogenization were present. It can be concluded that LLLT has shown efficacy in the treatment of periodontitis in diabetics. Because of more pronounced alterations of periodontium in diabetics, the use of LLLT is of particular importance. PMID- 22311660 TI - A topotactic synthetic methodology for highly fluorine-doped mesoporous metal oxides. PMID- 22311661 TI - Cannabinoid receptor 1 signaling in embryo neurodevelopment. AB - In utero exposure to tetrahydrocannabinol, the psychoactive component of marijuana, is associated with an increased risk for neurodevelopmental defects in the offspring by interfering with the functioning of the endocannabinoid (eCB) system. At the present time, it is not clearly known whether the eCB system is present before neurogenesis. Using an array of biochemical techniques, we analyzed the levels of CB1 receptors, eCBs (AEA and 2-AG), and the enzymes (NAPE PLD, DAGLalpha, DAGLbeta, MAGL, and FAAH) involved in the metabolism of the eCBs in chick and mouse models during development. The findings demonstrate the presence of eCB system in early embryo before neurogenesis. The eCB system might play a critical role in early embryogenesis and there might be adverse developmental consequences of in utero exposure to marijuana and other drugs of abuse during this period. PMID- 22311662 TI - Dual emission from rhenium(I) complexes induced by an interligand aromatic interaction. AB - A series of rhenium(I) diimine complexes cis,trans [Re(dmb)(CO)(2)(PR(1)R(2)R(3))(PR(4)R(5)R(6))](+) (dmb=4,4'-dimethyl-2,2' bipyridine, R(n)=phenyl or alkyl), each of which bears two phosphine ligands with various numbers of phenyl groups, has been synthesized by using the photochemical ligand-substitution reaction. Detailed studies of the structural features, not only in the crystal but also in solution, indicate that the number of phenyl groups is a crucial factor in controlling the rotational conformation of the phosphine ligands, which in turn determines the extent of the pi-pi interaction between the aromatic diimine ligand and the phenyl group(s). The pi-pi interaction strongly affected both electrochemical and photophysical properties: 1) the oxidation power of the Re complex became stronger, 2) the lifetime of the excited state became longer, and 3) the Stokes shift between the (1) MLCT absorption band and emission from the corresponding (3) MLCT excited state became smaller. In particular, the diphenyl and triphenyl phosphine had much greater influence on the properties than the monophenyl phosphine ligand. Dual emission was observed from the different rotational conformers of the complexes with an intermediate number of phenyl groups in the phosphine ligands. PMID- 22311663 TI - The Role of Helicobacter pylori in Upper Respiratory System Infections: Is it More Than Colonization? AB - Helicobacter pylori (HP) is recognized as a common chronic human bacterial infection and is the most common cause of gastritis. Recent studies suggest an increased HP prevalence in patients with various extra-digestive inflammatory diseases. Since many respiratory diseases are characterized by chronic inflammation as well as increased immune response, and HP may enter the nasopharyngeal cavity by gastroesophageal reflux, an association between respiratory disorders and HP infection has been suggested. Several studies discover HP in clinical samples from the patients with upper respiratory system infections. Even some of them revealed a relief after the treatment directed to HP eradication. However some studies do not support this theory and whether this association means a definite proof of a causal relationship between HP and respiratory diseases needs to be clarified. In this study, we aimed to review the reports about the role of HP in upper respiratory system infections. PMID- 22311664 TI - Herpes diagnostic tests and their use. AB - Genital Herpes is common, causes a broad spectrum of clinical disease, and enhances susceptibility to other sexually transmitted infections, including HIV. Accurate diagnosis of Herpes Simplex Virus infection is important in surveillance, diagnosis and management, screening, and quality assurance. We have reviewed currently available herpes diagnostics and their appropriate use. PMID- 22311665 TI - Topical treatment of chronic suppurative otitis media. AB - Chronic suppurative otitis media (CSOM) is a chronic inflammation of the middle ear and mastoid cavity presenting with ear discharge or otorrhea through a non intact tympanic membrane. CSOM is the most common cause of childhood hearing impairment in developing countries. Accurate diagnosis depends on a high index of suspicion, micro-otoscopic examination, and judicious use of imaging as required. CSOM can be classified into 3 types: tubotympanic, atticoantral, and post tympanostomy tube insertion. Aerobes, anaerobes and fungi are all potential pathogens in CSOM. This review summarizes the results of recent studies on the bacteriology of CSOM, biofilms, and the role of the nasopharynx pathogens that may have important implications for the treatment of this important pathology; that is often associated with misdiagnosis or delayed diagnosis. Particular emphasis will be placed on topical treatment options including choices of antibiotic, antifungal, and antiseptic agents, delivery technique, spectrum of activity, and risk of ototoxicity. PMID- 22311666 TI - The increased risk of community-acquired methicillin-resistant Staphylococcus aureus in neck infections in young children. AB - An increase in the isolation rate of methicillin-resistant Staphylooccus aureus (MRSA) in pediatric deep space neck infections including abscesses has been noted in recent years. A recent study by Duggal et al. [9] analyzed the microbiology of deep neck space in children and identify the possible risk factors. Patients younger than 16 months of age were 10 times more likely to have an S. aureus infection as compared to non S. aureus (P < .0001). MRSA comprised the majority of all S. aureus isolates (58%). The majority of community acquired -MRSA (80%) and methicillin sensitive S. aureus isolates (83%) were identified in lateral abscesses in contrast to the non-S. aureus isolates that were located medially (56%). African American pediatric patients accounted for 70% of all deep neck space infections, and 86% of all MRSA infections. Clindamycin resistance was detected in 8% (4/49) of all community-acquired MRSA isolates. The study illustrates significant differences in age and location of neck space infections as they relate to isolation of S. aureus. PMID- 22311667 TI - Current research on respiratory viral infections: XIIth International Symposium. AB - The XIIth International Symposium on Respiratory Viral Infections was convened by The Macrae Group (New York, NY, USA) in Taipei, Taiwan on 11-14 March 2010. This annual symposium provides a forum to discuss recent advances in respiratory virus research in an interdisciplinary fashion with specialists ranging from basic virology, epidemiology, vaccines, antivirals and management strategies. The 2010 symposium provided a detailed examination of lessons learned from the 2009 influenza pandemic with a common theme, emphasized by many speakers, being the importance of international collaboration and cooperation in responding to new infectious disease threats. PMID- 22311668 TI - Preliminary efforts directed toward the detection of craving of illicit substances: the iHeal project. AB - Many behavioral interventions, whether for the management of chronic pain, overeating, medication adherence, or substance abuse, are ineffective outside of the clinic or office environments in which they are taught. This lack of utility has spawned interest in enabling technologies that are capable of detecting changes in affective state that potentially herald a transition to risky behaviors. We have therefore undertaken the preliminary development of "iHeal", an innovative constellation of technologies that incorporates artificial intelligence, continuous biophysical monitoring, wireless connectivity, and smartphone computation. In its fully realized form, iHeal can detect developing drug cravings; as a multimedia device, it can also intervene as the cravings develop to prevent drug use. This manuscript describes preliminary data related to the iHeal Project and our experience with its use. PMID- 22311669 TI - Outcomes of unintentional beta-blocker or calcium channel blocker overdoses: a retrospective review of poison center data. AB - Outcomes following unintentional, supratherapeutic ingestions of a patient's own beta-blocker (BB) or calcium channel blocker (CCB) have not been well studied. A retrospective review of all poison control center (PCC) charts from January 2007 through December 2009 yielded 4,099 cases involving a BB or CCB. Of these, 436 (10.6%) met inclusion criteria. Data abstracted included patient age/gender, medication(s) involved, dose(s), time interval between ingestions, symptoms, and outcome. Exclusion criteria included intentional ingestions, ingesting someone else's medication, and ingestion intervals >12 h. Outcomes were defined as the development of symptoms, management site, hospital admission, and death. Mean age was 65.1 years (range 2-91; SD 17.9); 284 (65.1%) were women. Eighty-two (18.8%) cases resulted in ED evaluation; 44 (53.7%) of these were referred in by the PCC. Symptoms developed in 44 (10.1%) cases and 32 (7.3%) were admitted due to the ingestion. Of those admitted, five (15.6%) received treatment (three intravenous fluids, one glucagon, one calcium). Of the 343 (78.7%) cases initially observed on site, three (0.9%) were later referred to an ED; none required treatment. There was one death under extenuating circumstances. The validity of data abstraction was determined for six variable using 43 charts [0.97; 95% CI (0.91 0.99)]. Based on a retrospective analysis of PCC cases, home observation of asymptomatic patients following unintentional supratherapeutic ingestions of their own BB or CCB was safe in most cases. Further, prospective study is required to identify risks factors for becoming symptomatic or requiring treatment. PMID- 22311670 TI - Case files of the University of California San Francisco Medical Toxicology Fellowship: lamotrigine toxicity. PMID- 22311671 TI - Underage abortion and beyond: developments of Spanish law in competent minor's autonomy. AB - This paper examines the recent developments in underage abortion and related questions in Spanish law. Despite the prevalence of the language of autonomy, like in Britain, children's interests are not defined in Spain by relying exclusively on the competent child's views. Parental opinion and societal expectations are given due weight, although sometimes only implicitly. Calculated ambiguity in legal practice and in the relevant legal texts provides evidence of the pervasive influence of deeply rooted distrust as against clear-cut rules favouring a young person's autonomy. PMID- 22311672 TI - Retinoic acid/alpha-interferon combination inhibits growth and promotes apoptosis in mantle cell lymphoma through Akt-dependent modulation of critical targets. AB - Mantle cell lymphoma (MCL) is characterized by a profound deregulation of the mechanisms controlling cell-cycle progression and survival. We herein show that the combination of 9-cis-retinoic acid (RA) and IFN-alpha induces marked antiproliferative and proapoptotic effects in MCL cells through the modulation of critical targets. Particularly, IFN-alpha enhances RA-mediated G(0)-G(1) cell accumulation by downregulating cyclin D1 and increasing p27(Kip1) and p21(WAF1/Cip1) protein levels. Furthermore, RA/IFN-alpha combination also induces apoptosis by triggering both caspases-8 and -9 resulting in Bax and Bak activation. In particular, RA/IFN-alpha treatment downregulates the antiapoptotic Bcl-xL and Bfl-1 proteins and upregulates the proapoptotic BH3-only Noxa protein. Sequestration of Mcl-1 and Bfl-1 by upregulated Noxa results in the activation of Bid, and the consequent induction of apoptosis is inhibited by Noxa silencing. Noxa upregulation is associated with nuclear translocation of the FOXO3a transcription factor as consequence of RA/IFN-alpha-induced Akt inhibition. Pharmacologic suppression of Akt, but not of TORC1, increases Noxa protein levels and downregulates Bfl-1 protein supporting the conclusion that the inhibition of the Akt pathway, the resulting FOXO3a activation and Noxa upregulation are critical molecular mechanisms underlying RA/IFN-alpha-dependent MCL cell apoptosis. These results support the potential therapeutic value of RA/IFN-alpha combination in MCL management. PMID- 22311673 TI - Receptor tyrosine kinase genes amplified in glioblastoma exhibit a mutual exclusivity in variable proportions reflective of individual tumor heterogeneity. AB - Intratumoral heterogeneity in human solid tumors represents a major barrier for the development of effective molecular treatment strategies, as treatment efficacies will reflect the molecular variegation in individual tumors. In glioblastoma, the generation of composite genomic profiles from bulk tumor samples has allowed one to map the genomic amplifications of putative genetic drivers and to prioritize therapeutic targeting strategies aimed at eradicating the tumor burden. Notably, amplification of multiple receptor tyrosine kinases (RTK) within a single tumor specimen obtained from patients is frequently observed. In this study, use of a detailed multicolor FISH mapping procedure in pathologic specimens revealed a mutual exclusivity of gene amplification in the majority of glioblastoma tumors examined. In particular, the two most commonly amplified RTK genes, EGFR and PDGFRA, were found to be present in variable proportions across the tumors, with one or the other gene predominating in certain areas of the same specimen. Our findings have profound implications for designing efficacious therapeutic regimens, as it remains unclear that how the cells with different gene amplification events contribute to disease propagation or the response to molecular targeted therapies. PMID- 22311674 TI - Rapamycin resistance is linked to defective regulation of Skp2. AB - The mammalian target of rapamycin (mTOR) plays a role in controlling malignant cellular growth. mTOR inhibitors, including rapamycin (sirolimus), are currently being evaluated in cancer trials. However, a significant number of tumors are rapamycin resistant. In this study, we report that the ability of rapamycin to downregulate Skp2, a subunit of the ubiquitin protein ligase complex, identifies tumors that are sensitive to rapamycin. RNA interference (RNAi)-mediated silencing of Skp2 in human tumor cells increased their sensitivity to rapamycin in vitro and inhibited the growth of tumor xenografts in vivo. Our findings suggest that Skp2 levels are a key determinant of antitumor responses to mTOR inhibitors, highlighting a potentially important pharmacogenomic marker to predict sensitivity to rapamycin as well as Skp2 silencing strategies for therapeutic purposes. PMID- 22311675 TI - Dissection of T-cell antigen specificity in human melanoma. AB - Tumor-infiltrating lymphocytes (TIL) isolated from melanoma patients and expanded in vitro by interleukin (IL)-2 treatment can elicit therapeutic response after adoptive transfer, but the antigen specificities of the T cells transferred have not been determined. By compiling all known melanoma-associated antigens and applying a novel technology for high-throughput analysis of T-cell responses, we dissected the composition of melanoma-restricted T-cell responses in 63 TIL cultures. T-cell reactivity screens against 175 melanoma-associated epitopes detected 90 responses against 18 different epitopes predominantly from differentiation and cancer-testis antigens. Notably, the majority of these responses were of low frequency and tumor-specific T-cell frequencies decreased during rapid expansion. A further notable observation was a large variation in the T-cell specificities detected in cultures established from different fragments of resected melanoma lesions. In summary, our findings provide an initial definition of T-cell populations contributing to tumor recognition in TILs although the specificity of many tumor-reactive TILs remains undefined. PMID- 22311676 TI - Ultraintense short-wavelength emission from ZnO-sheathed MgO nanorods induced by subwavelength optical resonance cavity formation: verification of previous hypothesis. AB - A recent paper reported that intense emissions with a range of wavelengths over a wide spectral range, from ultraviolet to infrared light, might be possible by sheathing MgO nanorods with a semiconducting material with an optimal sheath thickness. In addition, the paper hypothesized that an ultraintense short wavelength emission could be obtained by sheathing MgO nanorods with a ~17 nm ZnO thin film in the paper. In this study, we found that the intensity ratio of the near-band edge emission to the deep level emission (I(NBE)/I(DL)) of the MgO core/ZnO-shell nanorods with a mean shell layer thickness of 17 nm was as high as ~30, whereas the I(NBE)/I(DL) ratio of the bare-MgO nanorods was 0. This near band edge emission intensity enhancement by sheathing the MgO nanorods with ZnO is by far more significant than that by sheathing the ZnO nanorods with other materials including MgO. This is because subwavelength optical resonance cavities form in the MgO-core/ZnO-shell nanorods with faceted surfaces, whereas they do not form in the ZnO-core/MgO (or other material)-shell nanorods with no faceted surfaces. PMID- 22311677 TI - Dithienocyclopentathieno[3,2-b]thiophene hexacyclic arene for solution-processed organic field-effect transistors and photovoltaic applications. AB - We have developed a ladder-type dithienocyclopentathieno[3,2-b]thiophene (DTCTT) hexacyclic unit in which the central thieno[3,2-b]thiophene ring was covalently fastened to two adjacent thiophene rings through carbon bridges, thereby forming two connected cyclopentadithiophene (CPDT) units in a hexacyclic coplanar structure. This stannylated Sn-DTCTT building block was copolymerized with three electron-deficient acceptors, dibromo-thieno[3,4-c]pyrrole-4,6-dione (TPD), dibromo-benzothiadiazole (BT), and dibromo-phenanthrenequinoxaline (PQX), by Stille polymerization, thereby furnishing a new class of alternating donor acceptor copolymers: PDTCTTTPD, PDTCTTBT, and PDTCTTPQX, respectively. Field effect transistors based on PDTCTTPQX and PDTCTTBT yielded high hole mobilities of 0.017 and 0.053 cm(2) V(-1) s(-1), respectively, which are among the highest performances among amorphous donor-acceptor copolymers. A bulk heterojunction solar cell that incorporated PDTCTTTPD with the lower-lying HOMO energy level delivered a higher V(oc) value of 0.72 V and a power conversion efficiency (PCE) value of 2.59%. PMID- 22311678 TI - Reproductive and neurobehavioral effects of clothianidin administered to mice in the diet. AB - Clothianidin was given in the diet to provide levels of 0% (control), 0.003%, 0.006%, and 0.012% from 5 weeks of age of the F(0) generation to 11 weeks of age of the F(1) generation in mice. Selected reproductive and neurobehavioral parameters were measured. In exploratory behavior in the F(0) generation, average time of movement, number of rearing, and rearing time of adult males increased significantly in a dose-related manner. There was no adverse effect of clothianidin on litter size, litter weight, or sex ratio at birth. The average body weight of male and female offspring was increased significantly in a dose related manner during the early lactation period. With respect to behavioral developmental parameters, swimming head angle at postnatal day (PND) 7 of male offspring was accelerated significantly in a dose-related manner. Negative geotaxis at PND 7 of female offspring was accelerated significantly in a dose related manner. For movement activity of exploratory behavior in the F(1) generation, number of rearing of female offspring increased significantly in a dose-related manner. Movement time of adult males increased significantly in a dose-related manner. The dose levels of clothianidin in the present study produced several adverse effects in neurobehavioral parameters in mice. Nevertheless, it would appear that the levels of the actual dietary intake of clothianidin are unlikely to produce adverse effects in humans. PMID- 22311679 TI - A feasibility study of outpatient chemotherapy with S-1 + cisplatin in patients with advanced gastric cancer. AB - BACKGROUND: Regimens of standard-dose cisplatin have usually been administered as inpatient chemotherapy in Japan. This prospective study evaluated the feasibility of outpatient chemotherapy with standard-dose cisplatin in Japanese patients with advanced gastric cancer. METHODS: Advanced gastric cancer patients received an S 1 + cisplatin regimen (S-1: 80-120 mg days 1-21; cisplatin: 60 mg/m(2) day 8, every 4-5 weeks), either as outpatient chemotherapy with oral hydration on days 9 10, or as inpatient chemotherapy with intravenous hydration on days 9-10, based on the results of an oral hydration test during days 1-7 of the first cycle. The primary endpoint was the completion rate of two cycles in the outpatient group. RESULTS: A total of 36 patients were enrolled: 32 were allocated to the outpatient group and 4 to the inpatient group. The completion rate of two cycles in the outpatient group was 78% [90% confidence interval (CI): 63-89]. The median of the total number of treatment cycles of S-1 + cisplatin and the median progression-free survival in the outpatient group were 5 (range 1-11) and 10.6 months (95% CI 4.2-16.9), respectively. Although seven patients in the outpatient group discontinued treatment, mainly owing to gastrointestinal toxicity, most of them could continue S-1 + cisplatin by switching to inpatient chemotherapy from the next cycle. CONCLUSION: Outpatient chemotherapy with S-1 + cisplatin in advanced gastric cancer patients can be safely and effectively administered in Japan with appropriate patient selection and supportive treatment. PMID- 22311680 TI - Neuraminidase inhibitor resistance in influenza viruses and laboratory testing methods. AB - Infection with influenza viruses, including seasonal, avian and pandemic viruses, remains a worldwide public health problem. Although influenza virus infection is both vaccine preventable and drug treatable, high rates of mutation and reassortment of viruses can result in reduced effectiveness of vaccines or drugs. Currently, two classes of drugs, adamantanes (M2 blockers) and neuraminidase (NA) inhibitors (NAIs), are available for treatment and chemoprophylaxis of influenza infections. Given these limited antiviral therapy options, resistance to anti influenza drugs is a constant concern. The emergence and global spread of adamantane-resistant H3N2 viruses in 2003-2004 and oseltamivir-resistant seasonal H1N1 viruses in 2007-2009 demonstrated the ability of drug-resistant variants to rapidly become predominant worldwide. Since the 2009 H1N1 pandemic, all influenza viruses circulating in humans are M2-blocker-resistant and, in general, NAI susceptible. However, pandemic H1N1 viruses with resistance to the NAI oseltamivir have been reported. 'Permissive' drift mutations and reassortment of viral gene segments have been proposed as mechanisms underlying the retained replicative fitness of resistant viruses. Nevertheless, the precise role of these genetic changes in the efficient transmission and maintenance of resistant viruses in the absence of drug pressure remains poorly understood. In this review, we summarize NAI resistance in influenza viruses and discuss recent challenges in laboratory testing methods. Close monitoring of antiviral resistance among all influenza viruses, both locally and globally, are essential to inform public health strategies for the control of influenza infections. PMID- 22311681 TI - Density estimates of two endangered nocturnal lemur species from northern Madagascar: new results and a comparison of commonly used methods. AB - Very little information is known of the recently described Microcebus tavaratra and Lepilemur milanoii in the Daraina region, a restricted area in far northern Madagascar. Since their forest habitat is highly fragmented and expected to undergo significant changes in the future, rapid surveys are essential to determine conservation priorities. Using both distance sampling and capture recapture methods, we estimated population densities in two forest fragments. Our results are the first known density and population size estimates for both nocturnal species. In parallel, we compare density results from four different approaches, which are widely used to estimate lemur densities and population sizes throughout Madagascar. Four approaches (King, Kelker, Muller and Buckland) are based on transect surveys and distance sampling, and they differ from each other by the way the effective strip width is estimated. The fifth method relies on a capture-mark-recapture (CMR) approach. Overall, we found that the King method produced density estimates that were significantly higher than other methods, suggesting that it generates overestimates and hence overly optimistic estimates of population sizes in endangered species. The other three distance sampling methods provided similar estimates. These estimates were similar to those obtained with the CMR approach when enough recapture data were available. Given that Microcebus species are often trapped for genetic or behavioral studies, our results suggest that existing data can be used to provide estimates of population density for that species across Madagascar. PMID- 22311682 TI - The biology and clinical features of non-small cell lung cancers with EML4-ALK translocation. AB - The anaplastic lymphoma kinase (ALK) acts as a dominant oncogenic driver following chromosomal rearrangements in certain cancers including non-small cell lung cancer (NSCLC). NSCLC with ALK translocation occurs in a specific subset of patients and results in unique clinical features. Crizotinib is a small molecule inhibitor of ALK kinase that has recently been approved by the FDA for the treatment of patients with ALK-positive NSCLC. Treatment with crizotinib results in clinical benefit rate of 85%-90% and a median progression-free survival of 9 10 months for this molecular subset of patients. Ongoing studies will define the impact of crizotinib on overall survival and provide insights into the resistance mechanisms and potential activation of alternate pathways. Heat shock protein 90 inhibitors also appear promising in the treatment of ALK-positive NSCLC patients, based on early results. This article reviews the characteristics, treatment, and ongoing research in patients with ALK-positive NSCLC. PMID- 22311683 TI - Robotic surgery for oropharynx cancer: promise, challenges, and future directions. AB - Epidemiologic studies have shown a rise in the incidence of oropharyngeal cancer without a corresponding increase in oral cavity cancers. These diverging trends are explained by human papilloma virus, which preferentially affects the oropharynx. Cancers resulting from this viral infection bear a better prognosis than those that are smoking-related. Treatment of oropharyngeal cancers has typically involved the use of radiation and chemotherapy to avoid the morbidity of mandibular splitting surgery. The use of transoral robotic surgery (TORS) has obviated the need for large-scale open approaches but still provides the pathologic staging data that is unavailable from non-surgical approaches. Although TORS is in its infancy, early functional and oncologic outcome data are promising. The complex management of oropharyngeal cancers should utilize the available treatment modalities to optimize outcomes and stratify patients to different treatment based on risk status. PMID- 22311684 TI - FGF receptor inhibitors: role in cancer therapy. AB - The fibroblast growth factor (FGF) signaling pathway is implicated as a key driver of tumor progression and growth via the dysregulation of cell proliferation, differentiation, survival, and angiogenesis in multiple tumor types. In addition, it may serve as a mechanism of resistance to antivascular endothelial growth factor targeted therapy. As such this pathway has emerged as a relevant therapeutic target, and several agents that can inhibit or modulate its signaling are in various stages of development. This review will summarize the current clinical status of agents targeting FGF receptors. In addition, strategies to accelerate the clinical development of these targeted agents will be presented. PMID- 22311685 TI - Silyl cation mediated conversion of CO2 into benzoic acid, formic acid, and methanol. PMID- 22311687 TI - Unusual photoreaction of triquinacene within self-assembled hosts. AB - Triquinacene is a concave tricyclic hydrocarbon with diverse photoreactivity. In the cavity of an electron-accepting molecular host, triquinacene was specifically photooxidized at the peripheral allylic position into an alcohol, 1 hydroxytriquinacene, via guest-to-host electron transfer. The unusual reactivity stems from the extremely electron-deficient triazine panel ligand of the host cage, which allows the cage to function as a good electron acceptor. Thus, self assembled coordination cages can serve not only as molecular-sized reaction vessels but also function electronically as redox media. Dissolved molecular oxygen is indispensable for the photoreaction and immediately traps a photogenerated radical. PMID- 22311686 TI - An analysis of exome sequencing for diagnostic testing of the genes associated with muscle disease and spastic paraplegia. AB - In this study, we assess exome sequencing (ES) as a diagnostic alternative for genetically heterogeneous disorders. Because ES readily identified a previously reported homozygous mutation in the CAPN3 gene for an individual with an undiagnosed limb girdle muscular dystrophy, we evaluated ES as a generalizable clinical diagnostic tool by assessing the targeting efficiency and sequencing coverage of 88 genes associated with muscle disease (MD) and spastic paraplegia (SPG). We used three exome-capture kits on 125 individuals. Exons constituting each gene were defined using the UCSC and CCDS databases. The three exome-capture kits targeted 47-92% of bases within the UCSC-defined exons and 97-99% of bases within the CCDS-defined exons. An average of 61.2-99.5% and 19.1-99.5% of targeted bases per gene were sequenced to 20X coverage within the CCDS-defined MD and SPG coding exons, respectively. Greater than 95-99% of targeted known mutation positions were sequenced to >=1X coverage and 55-87% to >=20X coverage in every exome. We conclude, therefore, that ES is a rapid and efficient first tier method to screen for mutations, particularly within the CCDS annotated exons, although its application requires disclosure of the extent of coverage for each targeted gene and supplementation with second-tier Sanger sequencing for full coverage. PMID- 22311688 TI - Facile preparation of free-standing carbon nanotube arrays produced using two step floating-ferrocene chemical vapor deposition. AB - A two-step floating-ferrocene chemical vapor deposition method has been devised for the preparation of single-layered aligned carbon nanotube (CNT) arrays. In the first step, uniform Fe catalysts are in situ produced and coated on a Si substrate from ferrocene; single-layered CNT arrays are prepared on these catalysts from ethylene in the second step. The effect of ferrocene loading on the distribution of Fe catalysts, as well as the morphology, diameter, and height of the CNT arrays, was investigated. A novel vacuum extraction process was employed to release the as-prepared CNT array from the Si wafer after water etching at 750 degrees C. The structural integrity of the free-standing arrays was preserved after the detachment process. The interface between the substrate and the as-grown CNT array was examined. The Fe catalyst distribution on the Si substrate remained homogeneous when the CNT array was removed, and the tops and bottoms of the arrays had different structures, suggesting that the arrays were formed predominantly by a base-growth mode. These free-standing arrays could potentially be applied in membrane or electronic applications. PMID- 22311689 TI - American Indian/Alaska Native cancer policy: systemic approaches to reducing cancer disparities. AB - Members of American Indian and Alaska Native (AI/AN) tribes have a unique political status in the United States in terms of citizenship, and that political status determines eligibility for certain unique healthcare services. The AI/AN population has a legal right to healthcare services based on treaties, court decisions, acts of Congress, Executive Orders, and other legal bases. Although the AI/AN population has a right to healthcare services, the Indian Health Service (the federal agency responsible for providing healthcare to AI/ANs) is severely underfunded, limiting access to services (including cancer care). In order to overcome distinct cancer health disparities, policy changes will be needed. This paper reviews the historical pattern of AI/AN healthcare and the challenges of the complex care needed from prevention through end-of-life care for cancer. PMID- 22311690 TI - Tobacco cessation intervention during pregnancy among Alaska Native women. AB - This paper describes a community-based participatory research program with Alaska Native people addressing a community need to reduce tobacco use among pregnant women and children. Tobacco use during pregnancy among Alaska Native women is described along with development of a community partnership, findings from a pilot tobacco cessation intervention, current work, and future directions. Among Alaska Native women residing in the Yukon Kuskokwim Delta region of western Alaska, the prevalence of tobacco use (cigarette smoking and/or use of smokeless tobacco) during pregnancy is 79%. Results from a pilot intervention study targeting pregnant women indicated low rates of participation and less than optimal tobacco abstinence outcomes. Developing alternative strategies to reach pregnant women and to enhance the efficacy of interventions is a community priority, and future directions are offered. PMID- 22311691 TI - Working with patients who are also seeing a traditional healer. PMID- 22311692 TI - Healing pathways: art therapy for American Indian cancer survivors. AB - There is a paucity of research addressing quality of life factors for American Indian and Alaska Native cancer survivors. Complementary forms of therapy, such as art therapy, are beginning to address quality of life factors through the "healing" arts for cancer survivors. The purpose of this mixed methods pilot was to explore the effects of culturally relevant art interventions on stress reduction for American Indian cancer survivors and their family members. Forty six adult participants attended one of three workshops held within two settlements of the Coharie tribe and one southeastern urban tribal center. The data collected consisted of a pretest and posttest State-Trait Personality Inventory (STPI) and artwork resulting from three directed interventions. The artwork was analyzed using qualitative coding methods; however, the scores from the STPI were inconclusive because the inventory was determined to be culturally biased. While statistical significance was not achieved, the findings from qualitative coding reinforced a native concept of wellness focusing on the complex interaction between mind, body, spirit, and context. This pilot study also demonstrated how a community-driven approach was instrumental in the development of the overall workshop format. An expansion of the pilot study is also presented with preliminary results available in 2012. PMID- 22311693 TI - Cancer prevention health services research: an emerging field. AB - In October 2009, The University of Texas MD Anderson Cancer Center hosted a symposium, "Future Directions in Cancer Prevention and Control: Workforce Implications for Training, Practice, and Policy." This article summarizes discussions and an Internet and literature review by the symposium's Health Services Infrastructure Working Group. We agree on the need for the recognition of Cancer Prevention Health Services Research (CP-HSR) as a unified research field. With advances in cancer screening and increased emphasis on preventive services under healthcare reform, there is a growing need for investigators with both cancer prevention and HSR expertise to consider the comparative effectiveness of cancer screening methods, the cost-effectiveness of early detection technologies, and the accessibility of preventive care for individuals at risk of cancer. Defining CP-HSR as a field will provide investigators with credibility and will serve to draw more researchers to the field. Increasing funding to train individuals in CP-HSR will be important to help meet the anticipated demand for investigators with this specialized multidisciplinary expertise. PMID- 22311694 TI - The future of the cancer prevention workforce: why health literacy, advocacy, and stakeholder collaborations matter. AB - In considering the role of the cancer prevention workforce in meeting the nation's future health care needs, it is vital to address the considerable gaps in information, communication, training, professional development, roles, and levels of collaboration among diverse disciplines, stakeholders, and constituencies. As part of an October 2009 symposium at The University of Texas MD Anderson Cancer Center entitled "Future Directions in Cancer Prevention and Control: Workforce Implications for Training, Practice, and Policy," the Health Policy and Advocacy Working Group was convened to discuss barriers to closing these gaps. Three major themes emerged from the group's deliberations and are discussed here: (1) the role of critical health literacy and evidence-based collaborations in cancer prevention education, research, and practice; (2) the implications of health advocacy for policy development and clinical and public health practice; and (3) culturally and linguistically appropriate cancer prevention programs and information within advocacy/workforce collaborations. Mechanisms for addressing these gaps are presented. PMID- 22311696 TI - Non-contact AFM. PMID- 22311695 TI - Evaluation of reproductive disorders in female rats exposed to N-methyl-2 pyrrolidone. AB - BACKGROUND: N-methyl-2-pyrrolidone (NMP) is a solvent used in the petrochemical, and electronic industries, in pesticides production, veterinary drugs, and paint removers. The aim of study was to evaluate the relationship between the dose of NMP given orally and its effect on fertility in female rats and early development of their progeny. METHODS: Females were exposed by gavage 5 days/week to NMP at 150, 450, or 1000 mg/kg/day 2 weeks before mating, during mating, gestation, and lactation. On the first postnatal day (PND 1), the live and dead pups were counted, weighed, and gender was determined. On PND 4, the litters were culled to eight animals each and balanced for gender. Young animals were observed during 3 weeks after birth. RESULTS AND CONCLUSION: Fertility index did not significantly differ in the control and the group exposed at 150 mg/kg/day but it was significantly lower in the groups exposed at 450 or 1000 mg/kg/day. The number of live pups in the group exposed to the highest dose was significantly lower and the number of stillbirths in litters was significantly greater. Survival of the pups from all exposed groups during the 3 weeks after birth was significantly lower than the control animals. The results of our study indicate that intragastric exposure of female rats to NMP before pregnancy during gestation causes significant impairment in female fertility and intrauterine mortality rates. At lower doses, toxic or slightly toxic to the mothers, this substance causes decrease in viability and physical development of progeny. PMID- 22311697 TI - Cebus phylogenetic relationships: a preliminary reassessment of the diversity of the untufted capuchin monkeys. AB - The untufted, or gracile, capuchin monkeys are currently classified in four species, Cebus albifrons, C. capucinus, C. olivaceus, and C. kaapori, with all but C. kaapori having numerous described subspecies. The taxonomy is controversial and their geographic distributions are poorly known. Cebus albifrons is unusual in its disjunct distribution, with a western and central Amazonian range, a separate range in the northern Andes in Colombia, and isolated populations in Trinidad and west of the Andes in Ecuador and northern Peru. Here we examine previous morphological and molecular hypotheses of the taxonomy and phylogeny of Cebus. We construct a time-calibrated phylogeny based upon mitochondrial DNA sequences from 50 Cebus samples from across their range. Our data indicate that untufted capuchins underwent a radiation at about 2 Ma, and quickly diversified in both the Andes and the Amazon. We provide a provisional reassessment for the taxonomy of untufted capuchins in the Amazon, the Llanos, the Andes, Trinidad, and Central America, splitting currently paraphyletic taxa into several species, including: at least two Amazonian species (C. yuracus and C. unicolor); a species from the Guiana Shield (most likely the same as Humboldt's C. albifrons); two northern Andean species, C. versicolor, C. cesarae; C. brunneus (with trinitatis a junior synonym) on the Venezuelan coast, and C. adustus in the region of Lake Maracaibo; C. capucinus in northwestern Ecuador and Colombia, and Panama; C. imitator in Central America; C. olivaceus and C. castaneus occupying a large part of the Guiana Shield; and C. kaapori in the eastern Amazon, south of the Rio Amazonas. More intensive and extensive geographic sampling is needed, including that for some subspecies not represented here. Taxa from the southwestern Amazon (yuracus, cuscinus, and unicolor) and the phylogenetic position of Humboldt's Simia albifrons from the Orinoco remain particularly poorly defined. PMID- 22311698 TI - [Family caregivers and health promotion. Pilot study to validate a German assessment to survey resources and risks of elderly family caregivers (ARR)]. AB - The ARR is a German assessment instrument to survey physical and psychological resources and risks of elderly family caregivers (50+). Factor structure, reliability, and validity were investigated using a sample of 202 caregivers from a national health insurance company. The factorial validity was confirmed for the physical profile (PHP) and the psychological profile (PSP). Reliability is good (PHP: Cronbach's alpha=0.73; PSP: Cronbach's alpha=0.71) for the shortness of the profiles. The correlation with self-efficacy constitutes an indicator for construct validity. The psychometric qualities allow the conclusion that the ARR is a reliable and valid instrument which is of interest for family caregivers. Nevertheless, further testing of validity is required. PMID- 22311699 TI - The thinner the better: self-esteem and low body weight in anorexia nervosa. AB - The aim of the present study was to examine the associations between self-esteem, motive satisfaction, and body weight in acute (acAN) and recovered (recAN) inpatients with anorexia nervosa (AN) and in healthy controls. Both acAN and recAN showed lower levels of self-esteem as compared with healthy controls but did not differ from each other. In acAN, decreased body weight was associated with increased self-esteem. Satisfaction of an achievement motive but not satisfaction of a superiority motive mediated this association. No such correlations could be observed in the other groups. This is the first study to show an often assumed association between decreased body weight and increased self-esteem in AN patients. These preliminary results strengthen the assumption that low body weight may foster self-esteem in patients with acAN, mainly through the satisfaction of an achievement motive. KEY PRACTITIONER MESSAGE: Self-esteem should be focused very early in the treatment of AN since weight gain may deprive the patient of an important source of self-esteem. Treatment interventions should be attuned to underlying motives of threatened self-esteem; in AN patients, the enhancement of self-esteem via weight loss seems to be rather fuelled by the satisfaction of an achievement motive than by the satisfaction of a superiority motive. Specific trainings to improve self-esteem in AN patients seem to be promising as an add-on to regular treatment. PMID- 22311700 TI - Dual acquisition magic-angle spinning solid-state NMR-spectroscopy: simultaneous acquisition of multidimensional spectra of biomacromolecules. AB - Fast data collection: a general method for dual data acquisition of multidimensional magic-angle spinning solid-state NMR experiments is presented. The method uses a simultaneous Hartmann-Hahn cross-polarization from (1)H to (13)C and (15)N nuclei and exploits the long-living (15)N polarization for parallel acquisition of two multidimensional experiments. PMID- 22311701 TI - Health economics of interdisciplinary rehabilitation for chronic pain: does it support or invalidate the outcomes research of these programs? AB - Interdisciplinary rehabilitation has been shown to be effective for treatment of patients suffering from chronic nonmalignant pain with respect to activity level, pain intensity, function, or days of sick leave. However, effects in clinical outcome do not necessarily imply a superiority of the intervention from an economic point of view. Despite an increasing number of cost-utility and cost effectiveness studies, systematic reviews outline the methodological heterogeneity of studies, which makes it impossible to perform meta-analyses and to draw conclusions from the studies. Recent publications add interesting information to the current discussion; these studies cover the long-term development of sickness absence post-intervention and the cost effectiveness of workplace interventions, as well as a collaborative intervention in primary care. Much research has been done, and tendencies of effectiveness are visible, but there is still a long way to go to understand the economic implications of interdisciplinary rehabilitation from the perspectives of society, the health insurers, and the patients. PMID- 22311702 TI - Gold double-ring structures synthesized from block copolymer corpuscle templates. PMID- 22311703 TI - Enhanced performance of solution-processed amorphous LiYInZnO thin-film transistors. AB - Solution-processed, amorphous lithium-doped YInZnO (L-YIZO) thin-film transistors (TFTs) are investigated. An appropriate amount of Li doping significantly enhances the field-effect mobility in TFT performance (~15 times greater than that of nondoped YIZO) without controlled annealing under water vapor or O(3)/O(2) environments. The addition of Li into solution-processed YIZO semiconductors leads to improved film quality, which results from enriched metal oxygen bonding and reduced defect sites, such as oxygen vacancies and hydroxyl groups. Li doping of an amorphous ionic oxide semiconductor (AIOS) could serve as an effective strategy for low-temperature and high-performance solution-processed AIOS TFTs. PMID- 22311704 TI - C-reactive protein level predicts prognosis in patients with locoregionally advanced laryngeal carcinoma treated with chemoradiotherapy. AB - The aim of this study was to investigate the effect of C-reactive protein (CRP) level on the prognosis of patients with locoregionally advanced laryngeal carcinoma treated with chemoradiotherapy. Fifty-seven patients with locoregionally advanced laryngeal carcinoma (cT3-4, N0-3, M0) treated with chemoradiotherapy were reviewed retrospectively. Chemoradiotherapy comprised external beam radiotherapy to the larynx (70 Gy) with three cycles of cisplatin at 3-week intervals. Elevated CRP was defined as >8 mg/L. The survival rate was calculated using the Kaplan-Meier method, and a multivariate analysis was used to identify significant factors associated with prognosis, using a Cox proportional hazards model. During the median (range) follow-up of 5 years (1.3-5), 29 patients died from laryngeal cancer; the 5-year cancer-specific survival (CSS) rate was 49.12%. Fifteen patients had a high CRP level before chemoradiotherapy (>8 mg/L), and their CSS rate was significantly worse than that in the remaining patients (P = 0.003). Multivariate analysis showed that CRP and tumor site were independent prognostic indicators for CSS, with a hazard ratio of 2.66 (95% confidence interval (CI), 1.22-5.82; P = 0.014) and a hazard ratio of 1.67 (95% CI, 1.01-2.77; P = 0.045), respectively. Of those with elevated CRP, the CRP levels of ten patients became normal after chemoradiotherapy, of whom four were alive with no evidence of recurrence or metastasis during the follow-up. By contrast, all six with no CRP normalization after chemoradiotherapy died within 3.8 years. The elevation of CRP before treatment predicts a poor prognosis in patients with locoregionally advanced laryngeal carcinoma treated with chemoradiotherapy. PMID- 22311705 TI - The effect of adriamycin exposure on the notochord of mouse embryos. AB - The notochord has important structural and signaling properties during vertebrate development with key roles in patterning surrounding tissues, including the foregut. The adriamycin mouse model is an established model of foregut anomalies where exposure of embryos in utero to the drug adriamycin leads to malformations including oesophageal atresia and tracheoesophageal fistula. In addition to foregut abnormalities, treatment also causes branching, displacement, and hypertrophy of the notochord. Here, we explore the hypothesis that the notochord may be a primary target of disruption leading to abnormal patterning of the foregut by examining notochord position and structure in early embryos following adriamycin exposure. Treated (n = 46) and control (n = 30) embryos were examined during the crucial period when the notochord normally delaminates away from the foregut endoderm (6-28 somite pairs). Transverse sections were derived from the anterior foregut and analyzed by confocal microscopy following immunodetection of extracellular matrix markers E-cadherin and Laminin. In adriamycin-treated embryos across all stages, the notochord was abnormally displaced ventrally with prolonged attachment to the foregut endoderm. While E-cadherin was normally detected in the foregut endoderm with no expression in the notochord of control embryos, treated embryos up to 24 somites showed ectopic notochordal expression indicating a change in characteristics of the tissue; specifically an increase in intracellular adhesiveness, which may be instrumental in structural changes, affecting mechanical and signaling properties. This is consistent with disruption of the notochord leading to altered signaling to the foregut causing abnormal patterning and congenital foregut malformations. PMID- 22311706 TI - The aryl hydrocarbon receptor contributes to the proliferation of human medulloblastoma cells. AB - The aryl hydrocarbon receptor (AhR), a ligand-activated member of the basic helix loop-helix (bHLH)/PER-ARNT-SIM (PAS) transcription superfamily, is known to regulate the toxicity of polyaromatic halogenated hydrocarbon environmental chemicals, most notably dioxin. However, the AhR has also been implicated in multiple stages of tumorigenesis. Medulloblastoma (MB), a primary cerebellar brain tumor arising in infants and children, is thought to originate from abnormally proliferating cerebellar granule neuron precursors (GNPs). GNPs express high levels of the AhR in the external germinal layer of the developing cerebellum. Moreover, our laboratory has previously reported that either abnormal activation or deletion of the AhR leads to dysregulation of GNP cell cycle activity and maturation. These observations led to the hypothesis that the AhR promotes the growth of MB. Therefore, this study evaluated whether the AhR serves a pro-proliferative role in an immortalized MB tumor cell line (DAOY). We produced a stable AhR knockdown DAOY cell line [AhR short hairpin RNA (shRNA)], which exhibited a 70% reduction in AhR protein levels. Compared with wild-type DAOY cells, AhR shRNA DAOY cells displayed an impaired G(1)-to-S cell cycle transition, decreased DNA synthesis, and reduced proliferation. Furthermore, these cell cycle perturbations were correlated with decreased levels of the pro proliferative gene Hes1 and increased levels of the cell cycle inhibitor p27(kip1). Supplementation experiments with human AhR restored the proliferative activity in AhR shRNA DAOY cells. Taken together, our data show that the AhR promotes proliferation of MB cells, suggesting that this pathway should be considered as a potential therapeutic target for MB treatment. PMID- 22311707 TI - Cinnabarinic acid, an endogenous metabolite of the kynurenine pathway, activates type 4 metabotropic glutamate receptors. AB - Cinnabarinic acid is an endogenous metabolite of the kynurenine pathway that meets the structural requirements to interact with glutamate receptors. We found that cinnabarinic acid acts as a partial agonist of type 4 metabotropic glutamate (mGlu4) receptors, with no activity at other mGlu receptor subtypes. We also tested the activity of cinnabarinic acid on native mGlu4 receptors by examining 1) the inhibition of cAMP formation in cultured cerebellar granule cells; 2) protection against excitotoxic neuronal death in mixed cultures of cortical cells; and 3) protection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in mice after local infusion into the external globus pallidus. In all these models, cinnabarinic acid behaved similarly to conventional mGlu4 receptor agonists, and, at least in cultured neurons, the action of low concentrations of cinnabarinic acid was largely attenuated by genetic deletion of mGlu4 receptors. However, high concentrations of cinnabarinic acid were still active in the absence of mGlu4 receptors, suggesting that the compound may have off-target effects. Mutagenesis and molecular modeling experiments showed that cinnabarinic acid acts as an orthosteric agonist interacting with residues of the glutamate binding pocket of mGlu4. Accordingly, cinnabarinic acid did not activate truncated mGlu4 receptors lacking the N-terminal Venus-flytrap domain, as opposed to the mGlu4 receptor enhancer, N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a carboxamide (PHCCC). Finally, we could detect endogenous cinnabarinic acid in brain tissue and peripheral organs by high-performance liquid chromatography tandem mass spectrometry analysis. Levels increased substantially during inflammation induced by lipopolysaccharide. We conclude that cinnabarinic acid is a novel endogenous orthosteric agonist of mGlu4 receptors endowed with neuroprotective activity. PMID- 22311709 TI - Controlled transport through a single molecule. AB - We demonstrate how an electrode-molecule-electrode junction can be controllably opened and closed by careful tuning of the contacts' interspace and voltage. The molecule, an octanethiol, flips to bridge a ~1 nm interspace between substrate and scanning tunnelling microscope tip when an electric field exceeds a threshold (switch 'on'). Reducing the field below this threshold value leads to the reproducible detachment of the octanethiol (switch 'off'). Once contacted, a further reduction of the contacts' interspace leads to an increase of the conductance of the molecule. PMID- 22311708 TI - Extracellular signal-regulated kinase mitogen-activated protein kinase-dependent SOCS-3 gene induction requires c-Jun, signal transducer and activator of transcription 3, and specificity protein 3 transcription factors. AB - SOCS-3 gene induction by cAMP-elevating agents or the protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA), in primary HUVECs was found to require PKCeta- and PKCepsilon-dependent extracellular signal-regulated kinase (ERK) activation. The minimal, ERK-responsive element of the SOCS-3 promoter was localized to a region spanning nucleotides -107 to the transcription start site and contains conserved binding sites for AP-1 and SP1/SP3 transcription factors, as well as proximal and distal signal transducer and activator of transcription (pSTAT and dSTAT) binding elements. All three classes of transcription factor were activated in response to ERK activation. Moreover, representative protein components of each of these transcription factor binding sites, namely c-Jun, STAT3, and SP3, were found to undergo ERK-dependent phosphorylation within their respective transactivation domains. Mutational analysis demonstrated an absolute requirement for the SP1/SP3 binding element in controlling basal transcriptional activity of the minimal SOCS-3 promoter. In addition AP-1, pSTAT, and SP1/SP3 binding sites were required for ERK-dependent, PMA-stimulated SOCS-3 gene activation. The dSTAT site seems to be important for supporting activity of the AP-1 site, because combined deletion of both sites completely blocks transcriptional activation of SOCS-3 by PMA. Together these results describe novel, ERK-dependent regulation of transcriptional activity that requires codependent activation of multiple transcription factors within the same region of the SOCS-3 gene promoter. PMID- 22311710 TI - The quality of the childrearing environment of refugee or asylum-seeking children and the best interests of the child: reliability and validity of the BIC-Q. AB - The Best Interest of the Child Questionnaire (BIC-Q) has been designed as an instrument for screening the quality of the rearing situation of asylum-seeking or refugee children. It is intended to aid legal decisions in asylum procedures. The aim of this study was to determine the reliability and the construct validity of the BIC-Q. Based on a study sample of refugee or asylum-seeking children in the Netherlands (N = 74), the psychometric quality of the BIC-Q was investigated using Cohen's kappa for the inter- and intrarater reliability and a nonparametric item response model for the construct validity. The interrater and intrarater reliabilities of the BIC-Q were good (kappa = .65 and .74 respectively). The results of the item response model revealed that the 14 pedagogical environmental conditions formed a strong and valid measurement scale for the quality of the childrearing environment (H = .55; rho = .94). Preliminary results indicate that the BIC-Q may be applied to support decisions on where the asylum-seeking or refugee child has the best opportunities for development. PMID- 22311711 TI - Newly discovered Bale monkey populations in forest fragments in southern Ethiopia: evidence of crop raiding, hybridization with grivets, and other conservation threats. AB - Until recently, the Bale monkey (Chlorocebus djamdjamensis), an arboreal primate endemic to the southern Ethiopian highlands, remained virtually unstudied, and its distribution pattern inadequately documented. To broaden our knowledge of the species' distribution and abundance, we carried out interviews with local people and total count surveys for Bale monkeys across 67 fragmented forest sites in human-dominated landscapes in the Oromia and Southern Nations, Nationalities, and People's Regions, Ethiopia. From January 2010 to May 2011, we discovered 26 new Bale monkey populations inhabiting forest fragments at elevations ranging from 2,355 to 3,204 m asl. Across these populations, we recorded 37 groups ranging in size from 9 to 29 individuals (Mean = 19.5, SD = 4.5), for a total of 722 individuals. Black-and-white colobus monkeys (Colobus guereza) were sympatric with Bale monkeys at all sites, while grivet monkeys (Chlorocebus aethiops) were found only at sites where Bale monkeys did not occur. All of the newly discovered Bale monkey sites once contained bamboo forest, though at 35% of the sites bamboo forest had been eliminated during the past two decades. The persistence of Bale monkeys at fragmented sites lacking bamboo suggests greater habitat flexibility for the species than previously thought, though the long-term viability of populations both with and without bamboo remains uncertain. Human hunting in response to crop raiding, a behavior the monkeys engaged in at all sites, represents a major threat facing the newly discovered Bale monkey populations. Furthermore, despite their current lack of sympatry, apparently hybrid individuals between Bale monkeys and grivets were noted at three sites, posing yet another potential obstacle to Bale monkey conservation. Community conservation programs aimed at (1) protecting remaining habitat fragments, (2) planting bamboo and trees within and between fragments, and (3) reducing crop raiding represent the only hope for survival of the newly discovered Bale monkey populations. PMID- 22311712 TI - Soluble and tubular higher fullerenes that encapsulate metals. PMID- 22311713 TI - Chronic cerebrospinal venous insufficiency as a cause of multiple sclerosis: controversy and reality. AB - OPINION STATEMENT: Multiple sclerosis (MS) is a relapsing and progressive disorder of the central nervous system. It is characterized most commonly by episodes of clinical worsening, followed by clinical improvement. Pathologically, MS is associated with focal areas of myelin destruction, inflammation, and axonal transection ("demyelinating plaques") in the brain and spinal cord. Traditionally, MS has been considered an autoimmune disorder, with the primary pathophysiology arising from an errant immune system. Recent work has raised the possibility that MS is not caused primarily by an immune abnormality but may instead arise from venous anomalies affecting the jugular and/or azygos venous systems. This condition has been called chronic cerebrospinal venous insufficiency (CCSVI). It has been proposed that CCSVI may be pathogenic in MS, causing venous back pressure and iron deposition, with a secondary immune response. Some investigators have proceeded to unblinded nonrandomized angioplasty and stenting procedures in patients with CCSVI, with anecdotal reports of symptom improvement. Because of conflicting data on the presence of CCSVI and the absence of controlled trials of CCSVI intervention, the current standard of clinical care is neither to evaluate multiple sclerosis (MS) patients for CCSVI anomalies, nor to intervene with procedures to alter such anomalies. There is intense interest and ongoing work to evaluate the presence of venous anomalies in MS patients as well as in normal controls and patients with other neurologic conditions; to characterize such anomalies, if present; and to further understand whether the concept of a "backpressure" pathology is borne out by the evidence. If CCSVI is indeed a pathogenic mechanism for some subset of the MS population, this would dramatically change the focus of attention for therapeutic endeavors and monitoring for this population and would bring MS therapeutics firmly into the area of vascular intervention. On the other hand, the history of MS research contains many novel and potentially paradigm-shifting ideas that were later disproved by other investigators. PMID- 22311714 TI - Clues to detect tumor necrosis factor receptor-associated periodic syndrome (TRAPS) among patients with idiopathic recurrent acute pericarditis: results of a multicentre study. AB - BACKGROUND: The potential clinical expression of tumor necrosis factor receptor associated periodic syndrome (TRAPS), in the form of idiopathic recurrent acute pericarditis (IRAP) has not been explored in the medical literature. The aim of this study was to evaluate the incidence of TRAPS mutations in patients with recurrent pericarditis and identify possible clues to TRAPS diagnosis. METHODS: Therefore, 131 consecutive Caucasian IRAP patients were investigated for mutations of the TRAPS gene and prospectively evaluated. RESULTS: Out of 131 patients, 8 (6.1%) carried a mutation in the TNFRSF1A gene. Compared with those without genetic mutations, patients with TRAPS mutations had more frequently a positive family history for pericarditis and periodic fever syndromes (p < 0.001), a higher mean number of recurrences after the first year (p < 0.001), on colchicine treatment (p < 0.001), and a higher need of immunosuppressive therapies (p < 0.001). CONCLUSION: TRAPS is a cause of recurrent pericarditis in 6% of unselected cases with recurrent pericarditis. A positive family history for pericarditis or periodic fever syndromes, a poor response to colchicine, recurrences after the first year from the index attack or on colchicine treatment, as well as the need of immunosuppressive agents are clues of the possible presence of TNFRSF1A gene mutations in patients with recurrent pericarditis. PMID- 22311715 TI - Agricultural non-point source pollution in China: causes and mitigation measures. AB - Non-point source (NPS) pollution has been increasingly serious in China since the 1990s. The increases of agricultural NPS pollution in China is evaluated for the period 2000-2008 by surveying the literature on water and soil pollution from fertilizers and pesticides, and assessing the surplus nitrogen balance within provinces. The main causes for NPS pollution were excessive inputs of nitrogen fertilizer and pesticides, which were partly the result of the inadequate agricultural extension services and the rapid expansion of intensive livestock production with little of waste management. The annual application of synthetic nitrogen fertilizers and pesticides in China increased by 50.7 and 119.7%, respectively, during 1991-2008. The mitigation measures to reduce NPS pollution include: correct distortion in fertilizer prices; improve incentives for the recycling of organic manure; provide farmers with better information on the sound use of agro-chemicals; and tighten the regulations and national standards on organic waste disposal and pesticides use. PMID- 22311716 TI - Effect of body size on expression of Manduca sexta midgut genes. AB - Isometric growth of larval insect midgut predicts that the ratio of midgut surface area to body mass decreases as larvae grow. Gut tissue and gut content masses were measured in first through fifth instar Manduca sexta larvae. Wet mass of gut tissue increased in relationship to body mass with a scaling exponent of 0.85 compared to an exponent of 1.33 for gut content mass, suggesting that surface area becomes increasingly limiting in larger larvae. To test the hypothesis that compensation for the decrease in relative surface area of the midgut occurs by increased expression of membrane proteins, we compared midgut mRNA expression in fourth and fifth instar. Surveyed genes encoded apical membrane proteins with diverse functions, including the potassium amino acid transporter KAAT1, ion channel CAATCH1, aminopeptidase msAPN3, V-type H-ATPase E subunit, and cation chloride cotransporter masBSC. KAAT1 was expressed 300- to 1500-fold higher in middle and posterior midgut compared to anterior midgut. Expression of msAPN3 was approximately 200-fold higher in posterior midgut than middle midgut. Expression of KAAT1 was 2.3- to 3.1-fold higher in fifth compared to fourth-instar larvae, and masBSC expression was 1.3- to 1.9-fold higher in fifth-instar larvae. Expression of msAPN3 and V-ATPase, but not KAAT1, decreased as body mass increased within the fifth instar. Although the increased expression of KAAT1 and masBSC in fifth-instar larvae supports the hypothesis of increased membrane protein expression in larger larvae, results from the other genes do not support this hypothesis. PMID- 22311717 TI - Immunological advantages of everolimus versus cyclosporin A in liver-transplanted recipients, as revealed by polychromatic flow cytometry. AB - Several immunosuppressive drugs with different mechanisms of action are available to inhibit organ rejection after transplant. We analyzed different phenotypic and functional immunological parameters in liver-transplanted patients who received cyclosporin A (CsA) or Everolimus (Evr). In peripheral blood mononuclear cells (PBMC) from 29 subjects receiving a liver transplant and treated with two different immunosuppressive regimens, we analyzed T cell activation and differentiation, regulatory T cells (Tregs) and Tregs expressing homing receptors such as the chemokine receptor CXCR3. T cell polyfunctionality was studied by stimulating cells with the superantigen staphylococcal enterotoxin B (SEB), and measuring the simultaneous production of interleukin (IL)-2 and interferon (IFN) gamma, along with the expression of a marker of cytotoxicity such as CD107a. The analyses were performed by polychromatic flow cytometry before transplantation, and at different time points, up to 220 days after transplant. Patients taking Evr had a higher percentage of total CD4+ and naive CD4+ T cells than those treated with CsA; the percentage of CD8+ T cells was lower, but the frequency of naive CD8+ T cells higher. Patients taking Evr showed a significantly higher percentage of Tregs, and Tregs expressing CXCR3. After stimulation with SEB, CD8+ T cells from Evr-treated patients displayed a lower total response, and less IFN gamma producing cells. The effects on the immune system, such as the preservation of the naive T cell pool and the expansion of Tregs (that are extremely useful in inhibiting organ rejection), along with the higher tolerability of Evr, suggest that this drug can be safely used after liver transplantation, and likely offers immunological advantages. PMID- 22311718 TI - Decreased inward rectification of Kir2.1 channels is a novel mechanism underlying the short QT syndrome. PMID- 22311719 TI - Thrombospondin-1 in pulmonary arterial hypertension: what ails NOS? PMID- 22311720 TI - Measuring myocardial salvage. AB - The efficacy of cardioprotective strategies can be quantified by myocardial salvage as an indicator of therapeutic benefit. Salvage is calculated as the difference between the area at risk (AAR) and the final infarct size (FIS). AAR has been quantified by angiographic assessment followed by quantification of FIS by biochemical ischaemic markers or imaging modalities such as cardiovascular magnetic resonance (CMR). Angiographical methods may overestimate AAR and since methodological differences may exist between different modalities, the use of different modalities for estimating AAR and FIS may not be recommended. (99m)Technetium (Tc)-Sestamibi single-photon emission tomography (SPECT) allows quantification of AAR and FIS by tracer injection prior to revascularization and after 1 month, respectively. SPECT provides the most validated measure of myocardial salvage and has been utilized in multiple randomized clinical trials. However, SPECT is logistically challenging, expensive, and includes radiation exposure. More recently, a large number of studies have suggested that CMR can determine salvage in a single examination by combining measures of myocardial oedema in the AAR exposed to ischaemia reperfusion with FIS quantification by late gadolinium enhancement. The T1- and T2-weighted CMR approaches for quantification of AAR utilize non-contrast, early and late gadolinium enhancement techniques. The technical progress, high spatial resolution and the potential for retrospective quantification of the AAR makes CMR the most appropriate technique for assessment of myocardial salvage. However, the optimum CMR technique for assessment of myocardial AAR remains to be defined. Consequently, we recommend a comprehensive CMR protocol to ensure reliable assessment of myocardial salvage. PMID- 22311721 TI - Relation between the chemical force and the tunnelling current in atomic point contacts: a simple model. AB - The relation between the tunnelling current I(t) and the interaction energy/force E in an atomic-scale contact is discussed in the framework of a theoretical model established here. According to our model, we predict the existence of two characteristic scaling regimes, where the tunnelling current is either proportional to the interaction energy, I(t) ~ E, or to the square of the interaction energy, I(t) ~ E(2). We show that the existence of a given regime is basically controlled by two parameters: (i) the energy degeneracy Delta and (ii) the hopping t between electronic levels involved in the interaction process. In addition, we discuss the validity of the Bardeen method to determine the tunnelling current in the short tip-sample distances. PMID- 22311722 TI - Genetic epidemiology with a capital E: where will we be in another 10 years? AB - In a commentary on the evolution of the field of genetic epidemiology over the past 10 years, Khoury et al. (2011) highlight several important developments, including the emergence of evaluation of genetic discoveries for their translational utility and of standards for reporting genetic findings. In this companion to their article, I reflect on some of these trends and speculate about the direction of the field in the future. In particular, I emphasize the opportunities posed by novel technologies like next-generation sequencing and the biological insights emerging from integrative genomics, but I also question the utility of large consortia. The basic principles of population-based research and the importance of taking account of the environment remain important to the field. PMID- 22311723 TI - Determination of fetal age by ultrasonography in St. Kitts green monkeys. AB - Ultrasound assessments of fetal growth have been used in other species of primates to estimate fetal age, but there are no published morphometrics for the St. Kitts green monkey (Chlorocebus sabaeus), a species that has been important for studies of transplantation of fetal tissue into the brain as potential treatment for degenerative disease. Previous studies with other primate species have used relatively small numbers of pregnancies, measured repeatedly, to derive regressions for predicting fetal age from ultrasound studies. The present study derives data from 967 pregnancies, collected over a 9-year period, for predicting fetal age from ultrasound measurements of crown rump length, biparietal diameter, head circumference, abdominal circumference, and femur length in the St. Kitts green monkey. Linear and polynomial regressions were determined from pregnancies dated from a 3- to 4-day breeding period and confirmed in a second, independent group of pregnant monkeys with more extended breeding times to determine their accuracy for predicting fetal age. Although similar to morphometrics reported in other monkey species, there were some significant differences. These data will improve the estimates of fetal ages in previously published studies of St. Kitts green monkeys and provide more precise estimates of fetal age in studies of fetal development, genomics, and reproductive toxicology. PMID- 22311724 TI - Tumor tropism of intravenously injected human-induced pluripotent stem cell derived neural stem cells and their gene therapy application in a metastatic breast cancer model. AB - Human pluripotent stem cells can serve as an accessible and reliable source for the generation of functional human cells for medical therapies. In this study, we used a conventional lentiviral transduction method to derive human-induced pluripotent stem (iPS) cells from primary human fibroblasts and then generated neural stem cells (NSCs) from the iPS cells. Using a dual-color whole-body imaging technology, we demonstrated that after tail vein injection, these human NSCs displayed a robust migratory capacity outside the central nervous system in both immunodeficient and immunocompetent mice and homed in on established orthotopic 4T1 mouse mammary tumors. To investigate whether the iPS cell-derived NSCs can be used as a cellular delivery vehicle for cancer gene therapy, the cells were transduced with a baculoviral vector containing the herpes simplex virus thymidine kinase suicide gene and injected through tail vein into 4T1 tumor bearing mice. The transduced NSCs were effective in inhibiting the growth of the orthotopic 4T1 breast tumor and the metastatic spread of the cancer cells in the presence of ganciclovir, leading to prolonged survival of the tumor-bearing mice. The use of iPS cell-derived NSCs for cancer gene therapy bypasses the sensitive ethical issue surrounding the use of cells derived from human fetal tissues or human embryonic stem cells. This approach may also help to overcome problems associated with allogeneic transplantation of other types of human NSCs. PMID- 22311726 TI - Initial experience using a pelvic emergency simulator to train reduction in blood loss. AB - BACKGROUND: Because the average exposure of surgeons to pelvic injuries with life threatening hemorrhage is decreasing, training opportunities are necessary to prepare surgeons for the rare but highly demanding emergency situations. We have developed a novel pelvic emergency simulator to train surgeons in controlling blood loss. QUESTIONS/PURPOSES: We (1) described the design and use of the simulator; and (2) determined whether the simulator correctly identified proper and improper mechanical stabilization and bleeding control. METHODS: The device contained two tube systems. The tubes of the first system were passed through the disrupted sacroiliac joint and the symphysis. By reduction (manual traction on the leg) and compression (application of the C-clamp) of the disrupted pelvis, the tubes were pinched by the synthetic bones leading to a stop of simulated blood flow through the tubes of the first system. The tubes of the second system ended in a foam representing the presacral and paravesical venous plexus. By correct preperitoneal packing, the flow into the foam was stopped. Simulated bleeding was monitored by quantifying flow out of a fluid reservoir and flow into fluid samplers. RESULTS: The pelvic emergency simulator has been used for eight training sessions since 2002. Bleeding control by packing was achieved after 6 +/ 3 minutes. Total simulated blood loss during the training session was 1296 +/- 892 mL. CONCLUSIONS: Our data suggest the simulator can be used as a tool to train surgeons to reduce blood loss in severe pelvic ring injuries. PMID- 22311725 TI - Is helical blade nailing superior to locked minimally invasive plating in unstable pertrochanteric fractures? AB - BACKGROUND: Technical advancements have produced many challenges to intramedullary implants for unstable pertrochanteric fractures. Helical blade fixation of the femoral head has the theoretical advantages of higher rotational stability and cutout resistance and should have a lower rate of reoperation than a locked plating technique. QUESTIONS/PURPOSES: We asked whether (1) helical blade nailing reduces the rate of reoperation within 24 months compared with locked plating and (2) any of various preoperative, intraoperative, or postoperative factors predicted failure in these two groups. METHODS: We prospectively enrolled 108 patients with unstable pertrochanteric fractures in a surgeon-allocated study between November 2005 and November 2008: 54 with percutaneous compression plates (PCCP) and 54 with proximal femoral nail antirotation (PFNA). We evaluated patients regarding reoperation, mortality, and function. Seventy-four patients had a minimum followup of 24 months (mean, 26 months; range, 24-30 months). RESULTS: We found no differences in the number of reoperations attributable to mechanical problems in the two groups: PCCP = six and PFNA = five. Despite a greater incidence of postoperative lateral wall fractures with helical blade nailing, only postoperative varisation of the neck shaft angle and tip-apex distance (33 mm versus 28 mm) predicted reoperation. Mortality and function were similar in the two groups. CONCLUSIONS: Our data suggest unstable pertrochanteric fractures may be fixed either with locked extramedullary small-diameter screw systems to avoid lateral wall fractures or with the new intramedullary systems to avoid potential mechanical complications of a broken lateral wall. Tip-apex distance and preservation of the preoperative femoral neck-shaft angle are the key technical factors for prevention of reoperation. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID- 22311727 TI - High speed data processing for imaging MS-based molecular histology using graphical processing units. AB - Imaging MS enables the distributions of hundreds of biomolecular ions to be determined directly from tissue samples. The application of multivariate methods, to identify pixels possessing correlated MS profiles, is referred to as molecular histology as tissues can be annotated on the basis of the MS profiles. The application of imaging MS-based molecular histology to larger tissue series, for clinical applications, requires significantly increased computational capacity in order to efficiently analyze the very large, highly dimensional datasets. Such datasets are highly suited to processing using graphical processor units, a very cost-effective solution for high speed processing. Here we demonstrate up to 13* speed improvements for imaging MS-based molecular histology using off-the-shelf components, and demonstrate equivalence with CPU based calculations. It is then discussed how imaging MS investigations may be designed to fully exploit the high speed of graphical processor units. PMID- 22311728 TI - Enhanced in-source fragmentation in MALDI-TOF-MS of oligonucleotides using 1,5 diaminonapthalene. AB - The capability to rapidly and confidently determine or confirm the sequences of short oligonucleotides, including native and chemically-modified DNA and RNA, is important for a number of fields. While matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) has been used previously to sequence short oligonucleotides, the typically low fragmentation efficiency of in-source or post-source decay processes necessitates the accumulation of a large number of spectra, thus limiting the throughput of these methods. Here we introduce a novel matrix, 1,5-diaminonapthalene (DAN), for facile in-source decay (ISD) of DNA and RNA molecular anions, which allows for rapid sequence confirmation. d-, w-, and y-series ions are prominent in the spectra, complementary to the (a-B)- and w- ions that are typically produced by MALDI post-source decay (PSD). Results are shown for several model DNA and RNA oligonucleotides, including combinations of DAN-induced fragmentation with true tandem TOF MS (MS/MS) for pseudo-MS(3) and "activated-ion PSD." PMID- 22311729 TI - Drinking in snakes: resolving a biomechanical puzzle. AB - Snakes have long been thought to drink with a two-phase buccal-pump mechanism, but observations that some snakes can drink without sealing the margins of their mouths suggest that buccal pumping may not be the only drinking mechanism used by snakes. Here, we report that some snakes appear to drink using sponge-like qualities of specific regions of the oropharyngeal and esophageal mucosa and sponge-compressing functions of certain muscles and bones of the head. The resulting mechanism allows them to transport water upward against the effects of gravity using movements much slower than those of many other vertebrates. To arrive at this model, drinking was examined in three snake species using synchronized cine and electromyographic recordings of muscle activity and in a fourth species using synchronized video and pressure recordings. Functional data were correlated with a variety of anatomical features to test specific predictions of the buccal-pump model. The anatomical data suggest explanations for the lack of conformity between a buccal-pump model of drinking and the performance of the drinking apparatus in many species. Electromyographic data show that many muscles with major functions in feeding play minor roles in drinking and, conversely, some muscles with minor roles in feeding play major roles in drinking. Mouth sealing by either the tongue or mental scale, previously considered critical to drinking in snakes, is incidental to drinking performance in some species. The sponge mechanism of drinking may represent a macrostomatan exaptation of mucosal folds, the evolution of which was driven primarily by the demands of feeding. PMID- 22311730 TI - A second-generation total synthesis of spirastrellolide A methyl ester. AB - Marine macrolides: an improved second-generation total synthesis of the anticancer macrolide spirastrellolide A methyl ester has been achieved. The synthesis features a uniformly high level of stereocontrol combined with more expedient fragment assembly, and demonstrates a critical dependence of the crucial macrolactonization step on the substitution pattern of the C22-C24 linker region. PMID- 22311731 TI - Cardiac FKBP12.6 overexpression protects against triggered ventricular tachycardia in pressure overloaded mouse hearts. AB - Alterations in RyR2 function have been proposed as a major pathophysiological mechanism of arrhythmias and heart failure (HF). Cardiac FKBP12.6 overexpression protects against myocardial infarction-induced HF and catecholamine-promoted ventricular arrhythmias. We tested the hypothesis that FKBP12.6 overexpression protects against maladaptive LVH and triggered ventricular arrhythmias following transverse aorta constriction (TAC) in the mouse. The TAC-associated mortality rate was significantly lower in male transgenic (DT) than in Ctr mice (p < 0.05). TAC-associated maladaptive hypertrophy was blunted in DT mice especially 1 month post-TAC and their SERCA2a/PLB ratio remained unchanged 1 and 2 months post-TAC. Two months after TAC, trains of 30 stimuli (burst pacing) performed following isoproterenol injection (0.2 mg/kg, ip), induced VT in 50% of the TAC-Ctr and in none of the TAC-DT mice (p = 0.022). The increase in myocyte shortening and Ca(2+) spark frequency observed in sham-operated Ctr mice in response to 50 nM isoproterenol was reduced in DT mice, and abolished in TAC-DT mice. NCX1 function was reduced in Sham-DT and TAC-DT compared with Sham-Ctr and TAC-Ctr mice, respectively (p < 0.05 for the 2 comparisons). In mice killed after isoproterenol injection and burst pacing, RyR2 S2814 phosphorylation was decreased by 50% in TAC-DT versus TAC-Ctr mice (p < 0.05), with no change in RyR2 S2808 and PLB S16 and T17 phosphorylation. Cardiac FKBP12.6 overexpression in the mouse blunts pressure overload-induced maladaptive LV remodelling and protects against catecholamine-promoted burst pacing-induced ventricular tachycardia by decreasing cardiac sensitivity to adrenergic stress and RyR2 S2814 phosphorylation, and decreasing NCX1 activity. PMID- 22311732 TI - Chronic treatment with long acting phosphodiesterase-5 inhibitor tadalafil alters proteomic changes associated with cytoskeletal rearrangement and redox regulation in Type 2 diabetic hearts. AB - Diabetic patients are prone to metabolic perturbations that progressively contribute to structural, functional and proteomic alterations in the myocardium. Phosphodiesterase-5 (PDE-5) inhibitors exhibit cardioprotective effects against ischemic/reperfusion injury, however the effects of chronic administration of PDE 5 inhibitors, particularly under diabetic conditions, remain unknown. Hence, the present study was designed to identify novel protein targets related to long acting PDE-5 inhibitor tadalafil-induced cardioprotection in diabetes. Using two dimensional differential in-gel electrophoresis with 3 CyDye labeling and MALDI TOF/TOF tandem mass spectrometry we identified alterations in the expressions of cardiac proteins in diabetic db/db mice treated with tadalafil. Tadalafil reversed the coordinated alterations of cytoskeletal/contractile proteins such as myosin light chain (MLY) 2 and 4, myosin heavy chain alpha and myosin-binding protein C which contributes to contractile dysfunction. The expression of intermediate filament protein vimentin and extra-cellular matrix proteins like cysteine and glycine rich protein-3 and collagen type VI alpha were upregulated in db/db mice indicating cardiac remodeling in diabetes. These detrimental proteomic alterations were reflected in cardiac function which were reversed in tadalafil treated mice. Tadalafil also enhanced antioxidant enzyme glutathione S transferase Kappa-1 (GSKT-1) and downregulated redox regulatory chaperones like heat shock protein 8 (HSPA8), and 75 kD glucose regulatory protein (75GRP). Furthermore, tadalafil treatment significantly attenuated GSSG/GSH ratio and improved the metabolic status of db/db mice. Chronic treatment with tadalafil in db/db mice modulates proteins involved in cytoskeletal rearrangement and redox signaling of the heart, which may explain the beneficial effects of PDE-5 inhibition in diabetes. PMID- 22311733 TI - Diastolic tolerance to systolic pressures closely reflects systolic performance in patients with coronary heart disease. AB - In animal experiments, elevating systolic pressures induces diastolic dysfunction and may contribute to congestion, a finding not yet translated to humans. Coronary surgery patients (63 +/- 8 years) were studied with left ventricular (LV) pressure (n = 17) or pressure-volume (n = 3) catheters, immediately before cardiopulmonary bypass. Single-beat graded pressure elevations were induced by clamping the ascending aorta. Protocol was repeated after volume loading (n = 7). Consecutive patients with a wide range of systolic function were included. Peak isovolumetric LV pressure (LVP(iso)) ranged from 113 to 261 mmHg. With preserved systolic function, LVP elevations neither delayed relaxation nor increased filling pressures. With decreasing systolic function, diastolic tolerance to afterload progressively disappeared: relaxation slowed and filling pressures increased (diastolic dysfunction). In severely depressed systolic function, filling pressures increased even with minor LVP elevations, suggesting baseline load-dependent elevation of diastolic pressures. The magnitude of filling pressure elevation induced in isovolumetric heartbeats was closely and inversely related to systolic performance, evaluated by LVP(iso) (r = -0.96), and directly related to changes in the time constant of relaxation tau (r = 0.95). The maximum tolerated systolic LVP (without diastolic dysfunction) was similarly correlated with LVP(iso) (r = 0.99). Volume loading itself accelerated relaxation, but augmented afterload-induced upward shift of filling pressures (7.9 +/- 3.7 vs. 3.0 +/- 1.5; P < 0.01). The normal human response to even markedly increased systolic pressures is no slowing of relaxation and preservation of normal filling pressures. When cardiac function deteriorates, the LV becomes less tolerant, responding with slowed relaxation and increased filling pressures. This increase is exacerbated by volume loading. PMID- 22311734 TI - Optimal Percoll concentration facilitates flow cytometric analysis for annexin V/propidium iodine-stained ischemic brain tissues. AB - We sought to determine the optimal Percoll concentration for ischemic rat brain prepared for flow cytometric (FC) measurements. Animals were subjected to the right middle cerebral artery (MCA) occlusion, and were euthanized at 3, 12, 24, and 72 h after reperfusion onset. The brains were processed by different concentrations (unisolated, 20, 25, 30, or 40%) of Percoll and stained with annexin V/propidium iodine (PI). Ischemic brain damage was evaluated by FC analysis and image analysis for histologic sections. The relative susceptibility of different phenotypes of cells to necrotic and apoptotic damage were evaluated by the FC analyses for the immunohistochemistry, PI, and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-processed brain tissues. Our results showed that FC analysis effectively detected the extent and maturation of apoptotic/necrotic brain damage, and the results were consistent with those determined from histologic brain sections. Neuron was more vulnerable to apoptosis than glia, whereas both cellular phenotypes were compatible in susceptibility for necrotic cell death. Percoll at a low concentration (20%) could effectively remove tissue debris without affecting membranous integrity of the injured neurons. Conversely, high percentages of Percoll (30-40%) substantially increased membranous damage for the injured cells. These results supported the application of FC to determine the extent and progression in time, as well as relative phenotypes of apoptotic/necrotic cell deaths following ischemic damage. We highlighted the use of Percoll at low percentages to facilitate the removal of tissue debris and to improve membrane integrity preservation for the injured neurons. PMID- 22311735 TI - Synthetic gene transfer vectors II: back to the future. AB - The discovery of RNA interference has given a new lease on life to both the chemistry of oligonucleotides and chemical approaches for the intracellular delivery of nucleic acids. In particular, delivery of siRNA, whether in vitro for screening and target validation purposes or in humans as a new class of drugs, may revolutionize our approach to therapy. Their impact could equal that of the bioproduction and various uses of monoclonal antibodies today. Unfortunately, global pharmaceutical companies again seem to be waiting to buy the next Genentech or Genzyme of gene silencing rather than investing research and development into this promising area of research. Gene silencing encounters barriers similar to gene addition and hence may benefit from the extra decade of experience brought by gene therapy. "Chemical" transfection of cells in culture has become routine, and this Account discusses some of the reasons this success has not extended to nonviral gene therapy trials, most of which do not progress beyond the phase 2 stage. The author also discusses a (much debated) mechanism of nucleic acid cell entry and subsequent release of the polycationic particles into the cytoplasm. Both topics should be useful to those interested in delivery of siRNA. The move from gene therapy toward siRNA as an oligonucleotide-based therapy strategy provides a much wider range of druggable targets. Even though these molecules are a hundredfold smaller than a gene, they are delivered via similar cellular mechanisms. Their complexes with cationic polymers are less stable than those with a higher number of phosphate groups, which may be compensated by siRNA concatemerization or by chemical conjugation with the cationic carrier. Thus chemistry is again desperately needed. PMID- 22311736 TI - Insect prey foraging strategies in Callicebus oenanthe in northern Peru. AB - Titi monkeys (genus Callicebus) are small-bodied platyrrhines that supplement their predominantly frugivorous diet with variable amounts of leaves, seeds, and/or arthropod prey. Notable interspecific variation in the amount of insect prey in the diet has been observed in Callicebus, ranging from 0% to 20%. In this study, I investigate the degree and type of prey foraging in a little-known species, Callicebus oenanthe inhabiting a fragmented, secondary forest on the foothills of the Andes in northern Peru. I present data on prey type, prey search and capture techniques, substrate/vegetation use, foraging height, prey capture efficiency, and seasonal variation of insect prey foraging in one group of C. oenanthe observed from January to August 2005. Insect prey accounted for 22% of the diet, the highest amount reported for any Callicebus species to date, and insects from at least six different orders were included. C. oenanthe was mainly an investigative forager of hidden prey, manipulating easy-to-open substrates such as rolled up leaves, and hunted ant swarms and larger insects opportunistically. Insect foraging was predominant during the dry season (26%) and decreased during the wet season (13%). The study group foraged mostly in the understory (2-6 m) within vine-laden shrubs and trees, which may conform to an anti-predator strategy of crypticity. Overall the group had an 83% insect capture success rate. These data suggest that insect prey is an important part of the diet of C. oenanthe and may be especially notable during periods of resource scarcity. This study adds to the knowledge concerning insect prey foraging in Callicebus, which can have an important role in defining ecological strategies in the selection of secondary protein food resources within a given ecosystem. PMID- 22311737 TI - CD49f enhances multipotency and maintains stemness through the direct regulation of OCT4 and SOX2. AB - CD49f (integrin subunit alpha6) regulates signaling pathways in a variety of cellular activities. However, the role of CD49f in regulating the differentiation and pluripotency of stem cells has not been fully investigated. Therefore, in this study, human mesenchymal stem cells (hMSCs) were induced to form spheres under nonadherent culture conditions, and we found that the CD49f-positive population was enriched in MSC spheres compared with MSCs in a monolayer. The expression of CD49f regulated the ability of hMSCs to form spheres and was associated with an activation of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. Furthermore, the forced expression of CD49f modulated the proliferation and differentiation potentials of hMSCs through prolonged activation of PI3K/AKT and suppressed the level of p53. We showed that the pluripotency factors OCT4 and SOX2 were recruited to the putative promoter region of CD49f, indicating that OCT4 and SOX2 play positive roles in the expression of CD49f. Indeed, CD49f expression was upregulated in human embryonic stem cells (hESCs) compared with hMSCs. The elevated level of CD49f expression was significantly decreased upon embryoid body formation in hESCs. In hESCs, the knockdown of CD49f downregulated PI3K/AKT signaling and upregulated the level of p53, inducing differentiation into three germ layers. Taken together, our data suggest that the cell-surface protein CD49f has novel and dynamic roles in regulating the differentiation potential of hMSCs and maintaining pluripotency. PMID- 22311738 TI - Four applications of permutation methods to testing a single-mediator model. AB - Four applications of permutation tests to the single-mediator model are described and evaluated in this study. Permutation tests work by rearranging data in many possible ways in order to estimate the sampling distribution for the test statistic. The four applications to mediation evaluated here are the permutation test of ab, the permutation joint significance test, and the noniterative and iterative permutation confidence intervals for ab. A Monte Carlo simulation study was used to compare these four tests with the four best available tests for mediation found in previous research: the joint significance test, the distribution of the product test, and the percentile and bias-corrected bootstrap tests. We compared the different methods on Type I error, power, and confidence interval coverage. The noniterative permutation confidence interval for ab was the best performer among the new methods. It successfully controlled Type I error, had power nearly as good as the most powerful existing methods, and had better coverage than any existing method. The iterative permutation confidence interval for ab had lower power than do some existing methods, but it performed better than any other method in terms of coverage. The permutation confidence interval methods are recommended when estimating a confidence interval is a primary concern. SPSS and SAS macros that estimate these confidence intervals are provided. PMID- 22311739 TI - Spin-labeling magnetic resonance imaging detects increased myocardial blood flow after endothelial cell transplantation in the infarcted heart. AB - BACKGROUND: We quantified absolute myocardial blood flow (MBF) using a spin labeling MRI (SL-MRI) method after transplantation of endothelial cells (ECs) into the infarcted heart. Our aims were to study the temporal changes in MBF in response to EC transplantation and to compare regional MBF with contractile function (wall motion) and microvascular density. METHODS AND RESULTS: We first validated the SL-MRI method with the standard microsphere technique in normal rats. We then induced myocardial infarction in athymic rats and injected 5 million ECs (human umbilical vein endothelial cells) suspended in Matrigel or Matrigel alone (vehicle) along the border of the blanched infarcted area. At 2 weeks after myocardial infarction, MBF averaged over the entire slice (P=0.038) and in the infarcted region (P=0.0086) was significantly higher in EC versus vehicle group; the greater MBF was accompanied by an increase of microvasculature density in the infarcted region (P=0.0105 versus vehicle). At 4 weeks after myocardial infarction, MBF in the remote region was significantly elevated in EC treated hearts (P=0.0277); this was accompanied by increased wall motion in this region assessed by circumferential strains (P=0.0075). Intraclass correlation coefficients and Bland-Altman plot revealed a good reproducibility of the SL-MRI method. CONCLUSIONS: MBF in free-breathing rats measured by SL-MRI is validated by the standard color microsphere technique. SL-MRI allows quantification of temporal changes of regional MBF in response to EC treatment. The proof-of principle study indicates that MBF is a unique and sensitive index to evaluate EC mediated therapy for the infarcted heart. PMID- 22311740 TI - CD105 (Endoglin) exerts prognostic effects via its role in the microvascular niche of paediatric high grade glioma. AB - Paediatric high grade glioma (pHGG) (World Health Organisation astrocytoma grades III and IV) remains poor prognosis tumours, with a median survival of only 15 months following diagnosis. Current investigation of anti-angiogenic strategies has focused on adult glioblastoma multiforme (GBM) with phase III trials targeting vascular endothelial growth factor continuing. In this study we investigated whether the degree of vascularity correlated with prognosis in a large cohort of pHGG (n = 150) and whether different vessel markers carried different prognostic value. We found that CD105 (endoglin) had a strongly significant association with poor prognosis on multivariate analysis (p = <0.001). Supervised hierarchical clustering of genome wide gene expression data identified 13 genes associated with differential degrees of vascularity in the cohort. The novel angiogenesis-associated genes identified in this analysis (including MIPOL-1 and ENPP5) were validated by realtime polymerase chain reaction. We also demonstrate that CD105 positive blood vessels associate with CD133 positive tumour cells and that a proportion of CD105 positive vessel cells demonstrates co-positivity for CD133, suggesting that the recently described phenomenon of vasculogenic mimicry occurs in pHGG. Together, the data suggest that targeting angiogenesis, and in particular CD105, is a valid therapeutic strategy for pHGG. PMID- 22311741 TI - Peripheral nerve sheath tumors: the elegant chapter in surgical neuropathology. PMID- 22311742 TI - Flow cytometry in cancer stem cell analysis and separation. AB - In recent years, a special type of cancer cell--the cancer stem cell (CSC)--has been identified and characterized for different tumors. CSCs may be responsible for the recurrence of a tumor following a primarily successful therapy and are thought to bear a high metastatic potential. For the development of efficient treatment strategies, the establishment of reliable methods for the identification and effective isolation of CSCs is imperative. Similar to their stem cell counterparts in bone marrow or small intestine, different cluster of differentiation surface antigens have been characterized, thus enabling researchers to identify them within the tumor bulk and to determine their degree of differentiation. In addition, functional properties characteristic of stem cells can be measured. Side population analysis is based on the stem cell specific activity of certain ATP-binding cassette transporter proteins, which are able to transport fluorescent dyes out of the cells. Furthermore, the stem cell specific presence of aldehyde dehydrogenase isoform 1 can be used for CSC labeling. However, the flow cytometric analysis of these CSC functional features requires specific technical adjustments. This review focuses on the principles and strategies of the flow cytometric analysis of CSCs and provides an overview of current protocols as well as technical requirements and pitfalls. A special focus is set on side population analysis and analysis of ALDH activity. Flow cytometry-based sorting principles and future flow cytometric applications for CSC analysis are also discussed. PMID- 22311743 TI - Variation in the thermal parameters of Odontophrynus occidentalis in the Monte desert, Argentina: response to the environmental constraints. AB - We studied the variation of thermal parameters of Odontophrynus occidentalis between season (wet and dry) in the Monte desert (Argentina). We measured body temperatures, microhabitat temperatures, and operative temperatures; while in the laboratory, we measured the selected body temperatures. Our results show a change in the thermal parameters of O. occidentalis that is related to environmental constraints of their thermal niche. Environmental thermal constraints are present in both seasons (dry and wet), showing variations in thermal parameters studied. Apparently imposed environmental restrictions, the toads in nature always show body temperatures below the set point. Acclimatization is an advantage for toads because it allows them to bring more frequent body temperatures to the set point. The selected body temperature has seasonal intraindividual variability. These variations can be due to thermo-sensitivity of toads and life histories of individuals that limits their allocation and acquisition of resources. Possibly the range of variation found in selected body temperature is a consequence of the thermal environmental variation along the year. These variations of thermal parameters are commonly found in deserts and thermal bodies of nocturnal ectotherms. The plasticity of selected body temperature allows O. occidentales to have longer periods of activity for foraging and reproduction, while maintaining reasonable high performance at different temperatures. The plasticity in seasonal variation of the thermal parameters has been poorly studied, and is greatly advantageous to desert species during changes in both seasonal and daily temperature, as these environments are known for their high environmental variability. PMID- 22311744 TI - Carbon-centered radicals can transfer hydrogen atoms between amino acid side chains. PMID- 22311745 TI - Synthesis of a unique isoindoline/tetrahydroisoquinoline-based tricyclic sultam library utilizing a Heck-aza-Michael strategy. AB - The synthesis of a unique isoindoline- and tetrahydroisoquinoline (THIQ) containing tricyclic sultam library, utilizing a Heck-aza-Michael (HaM) strategy is reported. Both isoindoline and THIQ rings are installed through a Heck reaction on a vinylsulfonamide, followed by one-pot deprotection and intramolecular aza-Michael reaction. Subsequent cyclization with either paraformaldehyde condensation or 1,1'-carbonyldiimidazole coupling generates a variety of tricyclic sultams. Overall, a 160-member library of these sultams, together with their isoindolines/THIQ and secondary sulfonamides precursors, were constructed using this strategy. PMID- 22311746 TI - Introduction to special issue on capuchin evolution: comparing behavior, morphology, and genetics across species. PMID- 22311747 TI - Derivation and functional analysis of patient-specific induced pluripotent stem cells as an in vitro model of chronic granulomatous disease. AB - Chronic granulomatous disease (CGD) is an inherited disorder of phagocytes in which NADPH oxidase is defective in generating reactive oxygen species. In this study, we reprogrammed three normal unrelated patient's fibroblasts (p47(phox) and gp91(phox) ) to pluripotency by lentiviral transduction with defined pluripotency factors. These induced pluripotent stem cells (iPSC) share the morphological features of human embryonic stem cells, express the key pluripotency factors, and possess high telomerase activity. Furthermore, all the iPSC lines formed embryoid bodies in vitro containing cells originating from all three germ layers and were capable of teratoma formation in vivo. They were isogenic with the original patient fibroblasts, exhibited normal karyotype, and retained the p47(phox) or gp91(pho) (x) mutations found in the patient fibroblasts. We further demonstrated that these iPSC could be differentiated into monocytes and macrophages with a similar cytokine profile to blood-derived macrophages under resting conditions. Most importantly, CGD-patient-specific iPSC derived macrophages showed normal phagocytic properties but lacked reactive oxygen species production, which correlates with clinical diagnosis of CGD in the patients. Together these results suggest that CGD-patient-specific iPSC lines represent an important tool for modeling CGD disease phenotypes, screening candidate drugs, and the development of gene therapy. PMID- 22311748 TI - Risk factors for failure to return to the pre-fracture place of residence after hip fracture: a prospective longitudinal study of 444 patients. AB - INTRODUCTION: Long-term place of residence after hip fracture is not often described in literature. The goal of this study was to identify risk factors, known at admission, for failure to return to the pre-fracture place of residence of hip fracture patients in the first year after a hip fracture. METHODS: This is a prospective longitudinal study of 444 consecutive admissions of hip fracture patients aged >= 65 years. Place of residence prior to admission, at discharge, after 3 and 12 months was registered. Patients admitted from a nursing home (n = 49) were excluded from statistical analysis. Multivariable logistic regression analysis was performed, using age, gender, presence of a partner, ASA-score, dementia, anaemia at admission, type of fracture, pre-fracture level of mobility and level of activities of daily living (ADL) as possible risk factors. RESULTS: Two hundred eighty-nine patients lived in their own home, 31.8% returned at discharge, 72.9% at 3 months and 72.8% at 12 months. Age, absence of a partner, dementia, and a lower pre-fracture level of ADL or mobility were independent contributors to failure to return to their own home at discharge, 3 or 12 months. 106 patients lived in a residential home; 33.3% returned at discharge, 68.4% at 3 months and 64.4% at 12 months. Age was an independent contributor to failure to return to a residential home. CONCLUSIONS: Age, dementia and a lower pre-fracture level of ADL were the main significant risk factors for failure to return to the pre-fracture residence. As the 3- and 12-month return-rates were similar, 3-month follow-up might be used as an endpoint in future research. PMID- 22311749 TI - DIGE: past and future. AB - This chapter provides a brief historical perspective of the development of difference gel electrophoresis, from its inception to commercialization and beyond. PMID- 22311750 TI - The basics of 2D DIGE. AB - The technique of two-dimensional (2D) gel electrophoresis is a powerful tool for separating complex mixtures of proteins, but since its inception in the mid 1970s, it acquired the stigma of being a very difficult application to master and was generally used to its best effect by experts. The introduction of commercially available immobilized pH gradients in the early 1990s provided enhanced reproducibility and easier protocols, leading to a pronounced increase in popularity of the technique. However gel-to-gel variation was still difficult to control without the use of technical replicates. In the mid 1990s (at the same time as the birth of "proteomics"), the concept of multiplexing fluorescently labeled proteins for 2D gel separation was realized by Jon Minden's group and has led to the ability to design experiments to virtually eliminate gel-to-gel variation, resulting in biological replicates being used for statistical analysis with the ability to detect very small changes in relative protein abundance. This technology is referred to as 2D difference gel electrophoresis (2D DIGE). PMID- 22311751 TI - Multifluorescence 2D gel imaging and image analysis. AB - Although image acquisition and analysis are crucial steps within the multifluorescence two-dimensional gel electrophoresis workflow, some basics are frequently not carried out with the necessary diligence. This chapter should help to prevent easily avoidable failures during imaging and image preparation for comparative protein analysis. PMID- 22311752 TI - Assessing signal-to-noise in quantitative proteomics: multivariate statistical analysis in DIGE experiments. AB - All quantitative proteomics experiments measure variation between samples. When performing large-scale experiments that involve multiple conditions or treatments, the experimental design should include the appropriate number of individual biological replicates from each condition to enable the distinction between a relevant biological signal from technical noise. Multivariate statistical analyses, such as principal component analysis (PCA), provide a global perspective on experimental variation, thereby enabling the assessment of whether the variation describes the expected biological signal or the unanticipated technical/biological noise inherent in the system. Examples will be shown from high-resolution multivariable DIGE experiments where PCA was instrumental in demonstrating biologically significant variation as well as sample outliers, fouled samples, and overriding technical variation that would not be readily observed using standard univariate tests. PMID- 22311753 TI - Analysis of proteins using DIGE and MALDI mass spectrometry. AB - Difference gel electrophoresis (DIGE) is a common technique for characterizing differential protein expression in quantitative proteomics. Usually a combination of enzymatic digestion and peptide analysis by mass spectrometry is used to identify differentially expressed proteins following separation and statistical analysis by DIGE. In this chapter, methods for gel spot picking, enzymatic digestion, and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) for protein identification of DIGE-analyzed proteins are discussed. Two examples are given: first, a specific protein is used to test the sensitivity of the 2D DIGE/MALDI MS combination for protein quantification and identification, and second, several proteins with and without the labels typically used in DIGE are identified to demonstrate that these labels do not alter MS-based protein identification. Technical variations of protein gel spot preparation, in-gel digestion, and mass spectral protein identification are discussed. PMID- 22311754 TI - Synthesis and validation of cyanine-based dyes for DIGE. AB - The application of difference gel electrophoresis (DIGE), in particular its most common "minimal labeling" variety, utilizes N-hydroxysuccinimide esters of Cy2, Cy3, and Cy5 dyes, which are commercially available. We describe methods for the efficient synthesis of all three dyes from relatively inexpensive and commercially available precursors in only a few steps and with relatively high yields. In model DIGE experiments, the newly synthesized dyes proved to be indistinguishable from commercially available ones and have been shown to be stable for years while stored under argon as dry solids or after being dissolved in N,N-dimethylformamide. PMID- 22311755 TI - 2D DIGE saturation labeling for minute sample amounts. AB - The 2D DIGE technique, based on fluorophores covalently linked to amino acid side chain residues and the concept of an internal standard, has significantly improved reproducibility, sensitivity, and the dynamic range of protein quantification. In saturation DIGE, sulfhydryl groups of cysteines are labeled with cyanine dyes to completion, providing a so far unraveled sensitivity for protein detection and quantification in 2D gel-based proteomic experiments. Only a few micrograms of protein per 2D gel facilitate the analysis of about 2,000 analytes from complex mammalian cell or tissue samples. As a consequence, 2D saturation DIGE is the method of choice when only minute sample amounts are available for quantitative proteome analysis at the level of proteins rather than peptides. Since very low amounts of samples have to be handled in a reproducible manner, saturation DIGE-based proteomic experiments are technically demanding. Moreover, successful saturation DIGE approaches require a strict adherence to adequate reaction conditions at each step. This chapter is dedicated to colleagues already experienced in 2D PAGE protein separation and intends to support the establishment of this ultrasensitive technique in proteomic workgroups. We provide basic guidelines for the experimental design and discuss crucial aspects concerning labeling chemistry, sample preparation, and pitfalls caused by labeling artifacts. A detailed step-by-step protocol comprises all aspects from initial sample preparation to image analysis and statistical evaluation. Furthermore, we describe the generation of preparative saturation DIGE gels necessary for mass spectrometry-based spot identification. PMID- 22311756 TI - Proteomic analysis of redox-dependent changes using cysteine-labeling 2D DIGE. AB - Redox-modification of proteins plays an important role in the regulation of protein function and cellular physiology and in pathological conditions such as oncogenic activation, inhibition of tumor suppression, and ischemia reperfusion injury. This occurs, at least in part, through the reduction or oxidation of cysteine groups in these proteins resulting in the modulation of their activities. Herein, we focus on the development of a pair of cysteine-labeling iodoacetylated cyanine dyes (ICy3/5) for two-dimensional difference gel electrophoresis (2D DIGE) to monitor redox-dependent changes on cysteine residues. The method is applied to a cellular model of human mammary luminal epithelial cells treated with H(2)O(2) to induce oxidative stress. Differences in labeling are caused either by differential protein expression or from the loss or gain of reactive thiol groups of cysteines in response to oxidative stress. Proteins displaying differential labeling would then be picked for MS-based identification. In summary, this cysteine-labeling 2D-DIGE approach provides an MS-compatible and reproducible technique for identifying alterations in the expression and redox-modification of free thiol-containing proteins. PMID- 22311757 TI - Analysis of protein posttranslational modifications using DIGE-based proteomics. AB - Difference gel electrophoresis (DIGE) is most often used to assess relative changes in the expression levels of individual proteins in multiple complex samples, and this information is valuable in making inferences about relative protein activity. However, a protein's activity is not solely dependent upon its expression level. A change in activity may also be influenced by myriad posttranslational modifications (PTMs), including palmitoylation, ubiquitination, oxidation, and phosphorylation. In this chapter, we describe the use of DIGE to determine specific PTMs by introducing specific labels or changes in pI and/or molecular weight. PMID- 22311758 TI - Comparative analyses of protein complexes by blue native DIGE. AB - Classically, DIGE is carried out on the basis of two-dimensional (2D) IEF/SDS PAGE. This allows comparative analyses of large protein sets. However, 2D IEF/SDS PAGE only poorly resolves hydrophobic proteins and is not compatible with native protein characterizations. Blue native PAGE represents a powerful alternative. Combined with CyDye labeling, blue native DIGE offers several useful applications like quantitative comparison of protein complexes of related protein fractions. Here we present a protocol for fluorophore labeling of native protein fractions for separation by blue native PAGE. PMID- 22311759 TI - 2D DIGE analysis of protein extracts from muscle tissue. AB - 2D DIGE, two-dimensional difference gel electrophoresis, is a technology used to study the protein expression on two-dimensional gels. Protein samples are labeled with different color fluorescent dyes designed not to affect the relative migration of proteins during electrophoresis. Here, we describe the practical procedures necessary to perform a 2D DIGE experiment for a muscle tissue protein extract followed by CyDye DIGE fluors minimal labeling and the analysis of 2D DIGE gels for the assessment of quantitative differences. PMID- 22311760 TI - Combination of highly efficient hexapeptide ligand library-based sample preparation with 2D DIGE for the analysis of the hidden human serum/plasma proteome. AB - Blood serum/plasma samples provide the major source to identify diagnostically relevant or treatment response-related proteins. But its complexity and the enormous dynamic range hinders comprehensive analysis. Therefore, more detailed analysis, in particular, of low-abundant peptides/proteins requires extensive pre fractionation, which frequently influences the native composition and may lead to a loss of potentially important information. In order to overcome these barriers, we describe an innovative sample preparation tool utilizing combinatorial hexapeptide ligand libraries to efficiently enrich low-abundance proteins with a simple protocol. In contrast to the most common approaches based on the immuno depletion of antibody-targeted high-abundance proteins, this technology concentrates low-abundance proteins and concurrently reduces the high-abundance species. Thus, the dynamic range is compressed, and low-abundance proteins become more easily detectable. We show how this sample preparation technique can be easily combined with 2D DIGE analysis to enable more comprehensive and quantitative profiling of complex biological samples. PMID- 22311761 TI - 2D DIGE analysis of serum after fractionation by ProteoMinerTM beads. AB - Serum is a popular biofluid used for many protein biomarker discovery projects since the collection and processing of serum/plasma is relatively noninvasive and inexpensive. Unfortunately, the downstream analysis of serum/plasma is hampered severely by several high-abundant proteins which often interfere with the separation and detection of many of the proteins of lower abundance. Thus, a number of prefractionation methods have recently been developed with the view to reduce the dynamic range of these proteins. These include both dye- and immunoaffinity-based methods that are specifically designed to remove serum albumin. In this chapter, we describe an alternative method using ProteoMinerTM or Equalizer beads that is aimed at overcoming this problem in serum. This method uses a combinatorial library of hexapeptides bound to beads and works by binding proteins until saturation is reached. Thus, the high-abundant proteins will reach saturation quickly, while the lower-abundant proteins continue to bind. This results in a dramatic depletion of the most abundant proteins, with a concurrent concentration of the middle- to low-abundant proteins. PMID- 22311762 TI - Study design in DIGE-based biomarker discovery. AB - The DIGE technology allows the detection of small differences in the expression level of abundant proteins. Many diseases are associated with quantitative deviations of proteins which might represent useful biomarkers for diagnosis or prognosis. DIGE is therefore a highly convenient method for the characterization of disease-related expression changes. This chapter focuses on the study design in DIGE-based biomarker discovery. It introduces the statistical implications of testing thousands of proteins in parallel and discusses the solutions proposed by the literature. The outline provided in the method section tries to guide the researcher through the different statistical considerations, which have to be taken into account in biomarker detection. Special emphasis is given to the use of sample sizes of sufficient statistical power and to the statistical evaluation of the results. PMID- 22311763 TI - Comparative 2D DIGE analysis of the depleted serum proteome for biomarker discovery. AB - Serum is unarguably the most used diagnostic fluid. As it circulates throughout the body, leakage peptides/proteins from damaged and dying cells, host-response proteins including inflammatory mediators, and aberrant secretions from tumors and diseased tissues are released into serum, potentially providing a rich source of disease biomarkers. Here, a method for extending access to the serum proteome by removing highly abundant proteins prior to comparative two-dimensional difference gel electrophoresis (2D DIGE) and subsequent protein digestion for identification by mass spectrometry is described. PMID- 22311764 TI - Differential gel-based proteomic approach for cancer biomarker discovery using human plasma. AB - Two-dimensional fluorescence difference gel electrophoresis (2D DIGE) has become a general platform for analysis of various clinical samples such as biofluids and tissues. In comparison to conventional 2-D polyacrylamide gel electrophoresis (2D PAGE), 2D DIGE offers several advantages, such as accuracy and reproducibility between experiments, which facilitate spot-to-spot comparisons. Although whole plasma can be easily obtained, the complexity of plasma samples makes it challenging to analyze samples with good reproducibility. Here, we describe a method for decreasing protein complexity in plasma samples within a narrow pH range by depleting high-abundance plasma proteins. In combination with analysis of differentially expressed spots, trypsin digestion, identification of protein by mass spectrometry, and standard 2D PAGE and DIGE, this method has been optimized for comparison of plasma samples from healthy donors and patients diagnosed with hepatocellular carcinoma. PMID- 22311765 TI - 2D DIGE for the analysis of RAMOS cells subproteomes. AB - Overexpression of human polMU in a Burkitt's lymphoma-derived B cell line (RAMOS), in which somatic hypermutation (SHM) is constitutive, induced an increase in somatic mutations in the parental cell line (Nucleic Acids Res 32:5861-5873, 2004). To further study PolMU implications in SHM, a dominant negative (DN) mutant of PolMU (PolMU-DN) was generated which showed moderated overexpression of the PolMU-DN protein. The subcellular prefractionation was used to improve the detection of low-abundance proteins contained in membrane/organelles and nuclei, which are efficiently separated from high abundance proteins commonly found in the cytosol that might otherwise hamper analysis. Two-dimensional (2D) difference gel electrophoresis (DIGE) is a technique for comparative proteomics, which improves the reproducibility and reliability of differential protein expression analysis between samples. The standard sample included in every gel (Cy2) comprises equal amounts of each sample to be compared, and thus improves the accuracy of protein quantification between samples from different gels, allowing accurate detection of small differences in protein levels. The combination of this techniques allowed the detection in Fraction F2 (membrane/organelles) of 2,111 spots, 55 of them with significant variation (19 increased and 36 decreased in a ratio >2.0 or <-2.0), and in Fraction F3 (nuclear) of 2,416 spots, 80 of them with significant variation (51 increased and 29 decreased in a ratio >1.5 or <-1.5). PMID- 22311766 TI - Application of saturation labeling in lung cancer proteomics. AB - Cancer is a quite heterogeneous disease and each cancer type can be divided in different subentities. Normally this is done by pathologist using classical dye staining protocols or considering specific biomarkers. To identify new biomarkers, allowing a more specific diagnosis clinical tissue specimen is the material of choice. But the amount of clinical material obtained by resection or biopsy is often limited. In order to perform analytical studies with such scarce sample material, a sensitive analysis method is required. Using two-dimensional electrophoresis (2DE) for the analysis of small protein amounts, protein saturation labeling using fluorescence dyes has been successfully applied. Here, we describe the application of saturation labeling in combination with microdissection for the analysis of lung tumor cells and bronchial epithelium cells. The presented study demonstrates all relevant steps of differential proteome analysis with scarce protein amount: experimental design, manual microdissection, optimization of saturation labeling, 2DE, protein identification and validation. As a result, 32 non-redundant proteins could be identified to be differentially regulated between the respective tissue types and are candidate biomarkers for describing lung cancer in more detail. PMID- 22311767 TI - Proteomic profiling of the epithelial-mesenchymal transition using 2D DIGE. AB - Metastasis remains the primary cause of cancer patient death. Although the precise molecular mechanisms at play remain largely unknown, tumor progression is currently hypothesized to follow a series of sequential steps known as the metastatic cascade. An important component, thought to be involved early in this cascade, is the process known as epithelial-mesenchymal transition (EMT), whereby epithelial cells undergo morphogenetic alterations and acquire properties typical of mesenchymal cells. EMT confers a metastatic advantage to the cancer cells through the loss of cell-cell adhesion, enhanced proteolytic activity, and increased cell migration and invasiveness. This chapter describes the experimental workflow for the secretome analysis of MDCK cells undergoing oncogenic Ras, and Ras/TGF-beta-mediated EMT. To enable this comparison, serum free cell culture conditions were optimized, and a secretome purification methodology established. Secretome samples were then subjected to DIGE analysis to reveal and quantify proteins that are differentially expressed during EMT. The proteomic strategy detailed within successfully identified several EMT modulators and broadens our understanding of the extracellular facets of the EMT process. PMID- 22311768 TI - Method for protein subfractionation of cardiovascular tissues before DIGE analysis. AB - Difference gel electrophoresis (DIGE) (Electrophoresis 18, 2071-2077, 1997, 1) is widely used in cardiovascular research. However, the dynamic range limitations stemming from contaminating plasma proteins and highly abundant extracellular matrix components can make cardiovascular tissues difficult to analyze. Here we describe a novel methodology for biochemical subfractionation of cardiovascular tissues before DIGE analysis. PMID- 22311769 TI - Application of DIGE and mass spectrometry in the study of type 2 diabetes mellitus mouse models. AB - Knowledge of the differences between the amounts and types of protein that are expressed in diseased compared to healthy subjects may give an understanding of the biological pathways that cause disease. This is the reasoning behind the presented protocol, which uses difference gel electrophoresis (DIGE) to discover up- or down-regulated proteins between mice of different genotypes, or of those fed on different diets, that may thus be prone to develop diabetes-like phenotypes. Subsequent analysis of these proteins by tandem mass spectrometry typically facilitates their identification with a high degree of confidence. PMID- 22311770 TI - Evaluating the efficacy of subcellular fractionation of blast cells using live cell labeling and 2D DIGE. AB - Labeling of exposed cell surface proteins of live cells using CyDye DIGE fluor minimal dyes is an efficient strategy for cell surface proteome profiling and quantifying differentially expressed proteins in diseases. Here we describe a strategy to evaluate a two-step detergent-based protein fractionation method using live cell labeling followed by visualization of the fluorescently labeled cell surface proteins and fractionated proteins within a single 2D gel. PMID- 22311771 TI - DIGE analysis of plant tissue proteomes using a phenolic protein extraction method. AB - Two-dimensional difference gel electrophoresis is an invaluable technique for the analysis of plant proteomes. However, preparation of protein fractions from plant tissues is challenging due to the special features of plant cells: a robust cell wall, large vacuoles which often contain high concentrations of organic acids and a broad range of secondary metabolites like phenolic compounds and pigments. Therefore, protein preparation for difference gel electrophoresis (DIGE) analyses has to be adapted. Here, we describe both a phenolic protein extraction method for plant tissues and an adapted protocol for DIGE labeling of the generated fractions. PMID- 22311772 TI - Native DIGE of fluorescent plant protein complexes. AB - CyDye labeling and DIGE have not only been proven to work for soluble proteins but also at the level of whole membrane protein complexes. After complex solubilization and CyDye labeling, proteins can be separated by native PAGE which is often combined with SDS PAGE in a subsequent step. By this combination, sizes of complexes as well as their subunit composition can be compared after mixing samples from different physiological states. Plants interact specifically with light via protein-bound pigments. This can be used in combination with CyDye technology to extend the "classical" approach in plant research. As an example, chlorophyll can be excited for fluorescent scanning at the Cy5 excitation wavelength. This property can be used to identify pigment-binding plant complexes and complex subunits isolated from plastid membranes. In this protocol, we present a combination of the conventional CyDye labeling technique with 2D native/SDS PAGE and parallel scanning for CyDyes and fluorescence from endogenous bound chlorophyll for identification of pigment-binding complexes and complex subunits. PMID- 22311773 TI - An overview of 2D DIGE analysis of marine (environmental) bacteria. AB - Microbes are the "unseen majority" of living organisms on Earth and main drivers of the biogeochemical cycles in marine and most other environments. Their significance for an intact biosphere is bringing environmental bacteria increasingly into the focus of genome-based science. Proteomics is playing a prominent role for providing a molecular understanding of how these microbes work and for identifying the key biocatalysts involved in the major biogeochemical processes. This overview describes the major insights obtained from two dimensional difference gel electrophoresis (2D DIGE) analyses of specific degradation pathways, complex metabolic networks, cellular processes, and regulatory patterns in the marine aerobic heterotrophs Rhodopirellula baltica SH1 (Planctomycetes) and Phaeobacter gallaeciensis DSM 17395 (Roseobacter clade) and the anaerobic aromatic compound degrader Aromatoleum aromaticum EbN1 (Betaproteobacteria). PMID- 22311774 TI - Application of 2D DIGE in animal proteomics. AB - Two-dimensional electrophoresis (2 DE) is one of the most important proteomic tools and allows studying the complexity of proteomes of different origin. This chapter describes a setup for 2D DIGE with minimal labeling for qualitative and quantitative applications. It relies on homemade gels of medium size and in our hands has been found useful for a wide variety of separation problems involving complex protein mixtures of animal or human origin. The basic method is given for serum proteins of different species, but with minor modifications the method may be easily adapted to other sample materials (other body fluids, cells, tissues), conditions, or size. Examples are given for simple pattern comparisons (e.g., quality control, fast comparison of just two samples) as well as for quantitative applications to larger sample sets. PMID- 22311775 TI - Acute and persistent effects of pre- and posthatching thermal environments on growth and metabolism in the red-eared slider turtle, Trachemys scripta elegans. AB - Many ectotherms possess the capacity to survive a wide range of thermal conditions. Long-term exposure to temperature can induce acclimational and/or organizational effects, and the developmental stage at which temperature exposure occurs may affect the type, degree, and persistence of these effects. We incubated red-eared slider turtle embryos at three different constant temperatures (T(inc); 26.5, 28.5, 30.5 degrees C), then divided the resulting hatchlings between two water temperatures (T(water); 25, 30 degrees C). We calculated growth rates to assess the short- and long-term effects of thermal experience on this metabolically costly process. We also measured resting metabolic rate (RMR) at three body temperatures (T(body;) 26.5, 28.5, 30.5 degrees C) shortly after hatching and 6 months posthatching to characterize the degree and persistence of acclimation to T(inc) and T(water) . Hatchling RMRs were affected by T(body) and T(inc) , and fit a pattern consistent with positive but incomplete metabolic compensation to T(inc) . Average growth rates over the first 11 weeks posthatching were strongly affected by T(water) but only marginally influenced by T(inc) , and only at T(water) = 30 degrees C. Six-month RMRs exhibited strong acclimation to T(water) consistent with positive metabolic compensation. However, within each T(water) treatment, RMR fit patterns indicative of inverse metabolic compensation to T(inc) , opposite of the pattern observed in hatchlings. Average growth rates calculated over 6 months continued to show a strong effect of T(water) , and the previously weak effect of T(inc) observed within the 30 degrees C T(water) treatment became more pronounced. Our results suggest that metabolic compensation was reversible regardless of the life stage during which exposure occurred, and therefore is more appropriately considered acclimational than organizational. PMID- 22311776 TI - A study of the blue-light-dependent phosphorylation, degradation, and photobody formation of Arabidopsis CRY2. AB - Arabidopsis cryptochrome 2 (CRY2) is a blue-light receptor mediating blue-light inhibition of hypocotyl elongation and photoperiodic promotion of floral initiation. CRY2 is a constitutive nuclear protein that undergoes blue-light dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus, but the relationship between these blue-light-dependent events remains unclear. It has been proposed that CRY2 phosphorylation triggers a conformational change responsible for the subsequent ubiquitination and photobody formation, leading to CRY2 function and/or degradation. We tested this hypothesis by a structure-function study, using mutant CRY2-GFP fusion proteins expressed in transgenic Arabidopsis. We show that changes of lysine residues of the NLS (Nuclear Localization Signal) sequence of CRY2 to arginine residues partially impair the nuclear importation of the CRY2K541R and CRY2K554/5R mutant proteins, resulting in reduced phosphorylation, physiological activities, and degradation in response to blue light. In contrast to the wild-type CRY2 protein that forms photobodies exclusively in the nucleus, the CRY2K541R and CRY2K554/5R mutant proteins form protein bodies in both the nucleus and cytosol in response to blue light. These results suggest that photoexcited CRY2 molecules can aggregate to form photobody-like structure without the nucleus-dependent protein modifications or the association with the nuclear CRY2-interacting proteins. Taken together, the observation that CRY2 forms photobodies markedly faster than CRY2 phosphorylation in response to blue light, we hypothesize that the photoexcited cryptochromes form oligomers, preceding other biochemical changes of CRY2, to facilitate photobody formation, signal amplification, and propagation, as well as desensitization by degradation. PMID- 22311777 TI - Diurnal dependence of growth responses to shade in Arabidopsis: role of hormone, clock, and light signaling. AB - We investigated the diurnal dependence of the hypocotyl-growth responses to shade under sunlight-night cycles in Arabidopsis thaliana. Afternoon shade events promoted hypocotyl growth, while morning shade was ineffective. The lhy-D, elf3, lux, pif4 pif5, toc1, and quadruple della mutants retained the response to afternoon shade and the lack of response to morning shade while the lhy cca1 mutant responded to both morning and afternoon shade. The phyB mutant, plants overexpressing the multidrug resistance-like membrane protein ABCB19, and the iaa17/axr3 loss-of-function mutant failed to respond to shade. Transient exposure of sunlight-grown seedlings to synthetic auxin in the afternoon caused a stronger promotion of hypocotyl growth than morning treatments. The promotion of hypocotyl growth by afternoon shade or afternoon auxin required light perceived by phytochrome A or cryptochromes during the previous hours of the photoperiod. Although the ELF4-ELF3-LUX complex, PIF4, PIF5, and DELLA are key players in the generation of diurnal hypocotyl-growth patterns, they exert a minor role in the control of the diurnal pattern of growth responses to shade. We conclude that the strong diurnal dependency of hypocotyl-growth responses to shade relates to the balance between the antagonistic actions of LHY-CCA1 and a light-derived signal. PMID- 22311778 TI - Arabidopsis sucrose transporter SUT4 interacts with cytochrome b5-2 to regulate seed germination in response to sucrose and glucose. AB - It remains unknown whether a sucrose transporter mediates sugar signaling. Here, we report that the Arabidopsis (Arabidopsis thaliana) sucrose transporter SUT4 interacts with five members of the Arabidopsis cytochrome b5 (Cyb5) family, and sucrose represses the interaction between SUT4 and a Cyb5 member Cyb5-2/A. We observed that down-regulation of SUT4 and three cytochrome b5 members (Cyb5-2, Cyb5-4, and Cyb5-6) confers the sucrose- and glucose-insensitive phenotypes in the sucrose/glucose-induced inhibition of seed germination. The sut4 cyb5-2 double mutant displays slightly stronger sucrose/glucose-insensitive phenotypes than either the sut4 or cyb5-2 single mutant. We showed that the SUT4/Cyb5-2 mediated signaling in the sucrose/glucose-induced inhibition of seed germination does not require ABA or the currently known ABI2/ABI4/ABI5-mediated signaling pathway(s). These data provide evidence that the sucrose transporter SUT4 interacts with Cyb5 to positively mediate sucrose and glucose signaling in the sucrose/glucose-induced inhibition of seed germination. PMID- 22311779 TI - A dual mechanism controls nuclear localization in the atypical basic-helix-loop helix protein PAR1 of Arabidopsis thaliana. AB - PAR1 is an atypical basic-helix-loop-helix (bHLH) protein that negatively regulates the shade avoidance syndrome in Arabidopsis thaliana acting as a transcriptional cofactor. Consistently with this function, PAR1 has to be in the nucleus to display biological activity. Previous structure-function analyses revealed that the N-terminal region of PAR1 drives the protein to the nucleus. However, truncated forms of PAR1 lacking this region still display biological activity, implying that PAR1 has additional mechanisms to localize into the nucleus. In this work, we compared the primary structure of PAR1 and various related and unrelated plant bHLH proteins, which led us to suggest that PAR1 contains a non-canonical nuclear localization signal (NLS) in the N-terminal region. By overexpressing truncated and mutated derivatives of PAR1, we have also investigated the importance of other regions of PAR1, such as the acidic and the extended HLH dimerization domains, for its nuclear localization. We found that, in the absence of the N-terminal region, a functional HLH domain is required for nuclear localization. Our results suggest the existence of a dual mechanism for PAR1 nuclear localization: (1) one mediated by the N-terminal non-consensus NLS and (2) a second one that involves interaction with other proteins via the dimerization domain. PMID- 22311780 TI - Ligand-stabilized [P4]2+ cations. PMID- 22311781 TI - Clinical predictors of Fidelis lead failure: report from the Canadian Heart Rhythm Society Device Committee. AB - BACKGROUND: Approximately 268,000 Fidelis leads were implanted worldwide until distribution was suspended because of a high rate of early failure. Careful analyses of predictors of increased lead failure hazard are required to help direct future lead design and also to inform decision making on lead replacement. We sought to perform a comprehensive analysis of all potential predictors in a multicenter study. METHODS AND RESULTS: A total of 3169 Sprint Fidelis leads were implanted in 11 centers with a total of 251 failures. Lead failure rates at 3, 4, and 5 years were 5.3%, 10.6%, and 16.8%, respectively. The rate of lead failure continues to accelerate (P<0.001). There were 4 independent predictors of failure: center, sex, access vein, and previous lead failure. Women had a higher hazard of failure (hazard ratio 1.51; 95% confidence interval, 1.14-2.04; P=0.005). Both axillary and subclavian access increased the hazard of failure (P=0.007); hazard ratio for axillary was 1.94, (95% confidence interval, 1.23 3.04) and for subclavian 1.63 (95% confidence interval, 1.08-2.46). Previous lead failure increased the hazard of a subsequent Fidelis failure with a hazard ratio of 3.12 (95% confidence interval, 1.80-5.41; P<0.001). CONCLUSIONS: The rate of Fidelis failure continues to increase over time, with failures approaching 17% at 5 years. Women, patients with leads inserted via the subclavian or axillary vein, and those with a previous lead fracture were at greatest risk of Fidelis failure. Our data suggest that Fidelis replacement should be strongly considered at the time of generator replacement. PMID- 22311782 TI - Context-dependent enhancement of induced pluripotent stem cell reprogramming by silencing Puma. AB - Reprogramming of the somatic state to pluripotency can be induced by a defined set of transcription factors including Oct3/4, Sox2, Klf4, and c-Myc [Cell 2006;126:663-676]. These induced pluripotent stem cells (iPSCs) hold great promise in human therapy and disease modeling. However, tumor suppressive activities of p53, which are necessary to prevent persistence of DNA damage in mammalian cells, have proven a serious impediment to formation of iPSCs [Nat Methods 2011;8:409-412]. We examined the requirement for downstream p53 activities in suppressing efficiency of reprogramming as well as preventing persistence of DNA damage into the early iPSCs. We discovered that the majority of the p53 activation occurred through early reprogramming-induced DNA damage with the activated expression of the apoptotic inducer Puma and the cell cycle inhibitor p21. While Puma deficiency increases reprogramming efficiency only in the absence of c-Myc, double deficiency of Puma and p21 has achieved a level of efficiency that exceeded that of p53 deficiency alone. We further demonstrated that, in both the presence and absence of p21, Puma deficiency was able to prevent any increase in persistent DNA damage in early iPSCs. This may be due to a compensatory cellular senescent response to reprogramming-induced DNA damage in pre-iPSCs. Therefore, our findings provide a potentially safe approach to enhance iPSC derivation by transiently silencing Puma and p21 without compromising genomic integrity. PMID- 22311802 TI - Juvenile development, ecdysteroids and hemolymph level of metabolites in the spider Brachypelma albopilosum (Theraphosidae). AB - In the present work, juvenile development and physiological state of mygalomorph Brachypelma albopilosum were investigated by means of individual rearing under controlled conditions. Males required 4-5 years for development from first juvenile instar to adulthood, passing through 8 to 12 juvenile molts. Females developed to adults in 5-6 years with a variable juvenile molt number from 9 to 13. The development and growth of males and females took place in a similar way until the last juvenile molt leading to subadults. Ecdysteroids, total lipid, cholesterol, and protein concentrations increased along with the different development instars in both males and females. After the last juvenile molt, spiders presented morphological and biochemical sex differences. Subadult and adulthood males were smaller in size and weight than females; hemolymph levels of ecdysteroids, total lipids, cholesterol, and glucose were higher in males. These physiological and biochemical differences can be correlated to the different sexual development between males and females. PMID- 22311803 TI - Synthesis of 3-fluoro-3-aryl oxindoles: direct enantioselective alpha arylation of amides. PMID- 22311804 TI - Entrapment of protein in nanotubes formed by a nanochannel and ion-channel hybrid structure of anodic alumina. AB - The nanochannel (in a porous layer) and ion-channel (in a barrier layer) hybrid structure of anodic alumina is used as a protein-trapping device. The transmembrane potential drives the electromigration of the charged proteins (FITC labeled) into the nanochannels, but electromigration across the barrier layer is impossible due to the size-exclusion effect. As a result, the proteins can be continuously trapped in the nanochannels. PMID- 22311805 TI - Metallodendritic grafted core-shell gamma-Fe2O3 nanoparticles used as recoverable catalysts in Suzuki C-C coupling reactions. AB - The use of dendritic structures for the grafting of core-shell gamma Fe(2)O(3)/polymer 300 nm superparamagnetic nanoparticles (MNPs) has been performed with four metallodendrons that were functionalized with diphosphinopalladium complexes. The catalytic performance of these nanocatalysts was optimized for the Suzuki C-C cross-coupling reaction. These results demonstrated the importance of optimizing the catalytic efficiency of grafted MNPs by optimizing the dendritic structures and the nature of the peripheral phosphine ligands. All of these nanocatalysts showed remarkable reactivity towards bromoarenes and they were recovered and efficiently reused by magnetic separation with almost no loss of reactivity, even after 25 cycles. PMID- 22311806 TI - Rai is a new regulator of neural progenitor migration and glioblastoma invasion. AB - The invasive nature of glioblastoma (GBM) is one important reason for treatment failure. GBM stem/progenitor cells retain the migratory ability of normal neural stem/progenitor cells and infiltrate the brain parenchyma. Here, we identify Rai (ShcC/N-Shc), a member of the family of Shc-like adaptor proteins, as a new regulator of migration of normal and cancer stem/progenitor cells. Rai is expressed in neurogenic areas of the brain and its knockdown impairs progenitor migration to the olfactory bulb. Its expression is retained in GBM stem/progenitor cells where it exerts the same promigratory activity. Rai silencing in cancer stem/progenitor cells isolated from different patients causes significant decrease in cell migration and invasion, both in vitro and in vivo, providing survival benefit. Rai depletion is associated with alteration of multiple-signaling pathways, yet it always leads to reduced expression of proinvasive genes. PMID- 22311809 TI - Learning from "coffee rings": ordered structures enabled by controlled evaporative self-assembly. AB - Research into the evaporation of solutions is not only aimed at a better understanding the physics of evaporation, but increasingly at capitalizing on the extremely simple method it offers to assemble diverse nonvolatile solutes into complex ordered structures on the submicron and longer length scales. This Review highlights recent advances in evaporative assembly of confined solutions, focusing especially on recently developed approaches that provide structures with unprecedented regularity composed of polymers, nanoparticles, and biomaterials, by controlled evaporation-driven, flow-aided self-assembly. A broad range of variables that can control the deposition are explored and the future directions of this rich field are presented. PMID- 22311810 TI - The parent borylene: betwixt and between. PMID- 22311811 TI - Urea/transition-metal cooperative catalyst for anti-selective asymmetric nitroaldol reactions. PMID- 22311812 TI - Inverse and high CO2/C2H2 sorption selectivity in flexible organic-inorganic ionic crystals. PMID- 22311813 TI - A mechanochemical approach to deracemization. PMID- 22311814 TI - Ruthenium NHC catalyzed highly asymmetric hydrogenation of benzofurans. PMID- 22311816 TI - Annulus fibrosus tissue engineering using lamellar silk scaffolds. AB - Degeneration of the intervertebral disc (IVD) represents a significant muscular skeletal disease. Recently, scaffolds composed of synthetic, natural and hybrid biomaterials have been investigated as options to restore the IVD; however, they lack the hallmark lamellar morphological features of annulus fibrosus (AF) tissue. The goal of regenerating the disc is to achieve anatomical morphology as well as restoration of mechanical and biological function. In this study, two types of scaffold morphology formed from silk fibroin were investigated towards the goal of AF tissue restoration. The first design mimics the lamellar features of the IVD that are associated with the AF region. The second is a porous spongy scaffold that serves as a control. Toroidal scaffolds were formed from the lamellar and porous silk material systems to generate structures with an outer diameter of 8 mm, inner diameter of 3.5 mm and a height of 3 mm. The inter lamellar spacing in the lamellar scaffold was 150-250 um and the average pore sizes in the porous scaffolds were 100-250 um. The scaffolds were seeded with porcine AF cells and, after growth over defined time frames in vitro, histology, biochemical assays, mechanical testing and gene expression indicated that the lamellar scaffold generated results that were more favourable in terms of ECM expression and tissue function than the porous scaffold for AF tissue. Further, the seeded porcine AF cells supported the native shape of AF tissue in the lamellar silk scaffolds. The lamellar silk scaffolds were effective in the formation of AF-like tissue in vitro. PMID- 22311817 TI - Living with rotationplasty--quality of life in rotationplasty patients from childhood to adulthood. AB - BACKGROUND: Knowledge about the long-term sequelae of rotationplasty, in adults treated surgically in childhood for Osteosarcoma in the lower limb, mainly concerns function and performance; the aim of this study is to explore the experience and the Quality of Life (QoL) of the patients who underwent Rotationplasty from 1986 to 2006 in Italy. METHODS: Quantitative test: Administration SF-36 questionnaire to 20 subjects aged >=16 years. Qualitative test: Semi-structured interview recorded in 10 of these subjects. RESULTS: Greater well-being was found in the Mental Component Summary (MCS) scale of subjects aged over 24 years, with a score mean of 54.2 (+/-4.8), compared with that of those aged up to 24 years, with a mean score of 48.0 (+/-6.6), P = 0.04. Relational and emotional difficulty in adolescence, which had been partially overcome in adulthood, was revealed. CONCLUSIONS: The assessment of QoL by the SF 36 questionnaire was effective, and a correspondence was found between what emerged from the quantitative study and the contents of the interview. Knowing the strengths and weaknesses that were highlighted is indispensable for parents and operators when choosing among the various surgical options and to facilitate coming to terms with the injury and the "scars". PMID- 22311818 TI - Prognostic significance of intraoperative chemotherapy and extensive lymphadenectomy in patients with node-negative gastric cancer. AB - BACKGROUND AND OBJECTIVES: Despite a relatively better prognosis, patients with node-negative gastric cancer still suffer from metastasis and recurrence. To investigae the prognostic factors and appropriate therapies for these pN0 tumors, we analyzed the predictors and evaluated the impact of chemotherapy and extensive lymphadenectomy on survival. METHODS: Clinicopathologic features of 153 patients with pN0 gastric cancer were studied retrospectively. The prognostic factors were analyzed stratifying by pT1 and pT2-3 stage. The 5-year survival rate (5-YSR) of patients in different groups of chemotherapy and lymph nodes retrieved were compared. RESULTS: Multivariate analysis indicated pT, number of nodes retrieved, and chemotherapy as the independent predictors of advanced gastric cancer; anemia was the only independent predictor of early gastric cancer. Survival of patients with pT3 got improved significantly by intraoperative chemotherapy and retrieval of more than 25 nodes, but neither of them benefited patients with pT1-2. Moreover, in pT3 status, 5-YSR of patients with intraoperative chemotherapy was still poorer than those with postoperative chemotherapy and combined chemotherapy. CONCLUSIONS: In pN0 gastric cancers, prognostic factors differed significantly between early stage and advanced stage. For patients with pT3, besides curative gastrectomy and postoperative chemotherapy, it might be beneficial to perform intraoperative chemotherapy and extensive lymphadenectomy. PMID- 22311819 TI - RUNX3 methylation as a predictor for disease progression in patients with non muscle-invasive bladder cancer. AB - BACKGROUND AND OBJECTIVES: We have previously reported that RUNX3 inactivation by promoter hypermethylation correlated with advanced disease and poor clinical outcome in bladder cancer. In this study, we examined primary tumors from non muscle-invasive bladder cancer (NMIBC) patients in order to investigate the relationship between RUNX3 methylation and disease progression. METHODS: The association between the hypermethylation of RUNX3 and clinicopathological characteristics of 186 NMIBC samples was analyzed using methylation-specific polymerase chain reaction (MS-PCR). RESULTS: RUNX3 methylation was associated with increased tumor stage, grade, and number of tumors (each P < 0.05). Kaplan Meier estimates revealed significant differences in time to recurrence and progression based on RUNX3 methylation status (P = 0.043 and 0.006, respectively). RUNX3 methylation was an independent predictor of NMIBC progression on univariate and multivariate analysis. Combining tumor grade and RUNX3 methylation status demonstrated that patients with G3 tumors with RUNX3 methylation had a worse progression-free survival compared with the patients with lower-grade or unmethylated tumors [hazard ratio (HR), 19.450]. CONCLUSIONS: RUNX3 methylation status predicted the risk of NMIBC progression independently of tumor stage. In conjunction with tumor grade, RUNX3 methylation status in patients with NMIBC strongly predicts disease progression. PMID- 22311820 TI - Simultaneous liquid-liquid extraction of dibenzyl disulfide, 2,6-di-tert-butyl-p cresol, and 1,2,3-benzotriazole from power transformer oil prior to GC and HPLC determination. AB - 2,6-Di-tert-butyl-p-cresol (DBPC), dibenzyl disulfide (DBDS), and 1,2,3 benzotriazole (BTA) are additives that may be found concomitantly in the oil matrix of power transformer. DBPC and DBDS act as antioxidants while, BTA is a corrosion inhibitor that protects copper conductors inside the transformer unit from corrosion. A powerful analytical method is, therefore, required to determine these additives at trace levels in the transformer oil. This work describes a unique single liquid-liquid extraction pretreatment step prior to the determination of the components by gas chromatography (GC) and high-performance liquid chromatography (HPLC) techniques. The optimum volume ratio used in the pretreatment step was determined as 5:2:5 for mineral oil/n-hexane/acetonitrile, respectively. Relatively, the method is simple and quick with a minimal use of solvents. Analytical results indicate that the method is relatively sensitive, accurate, and precise for each of the three components in fresh and used mineral oil. The calibration curves for the three components demonstrate a significant increase in sensitivities. Detection limits found were, 100 mg L(-1) (0.01% w/v), 0.80 mg L(-1) , and 2.04 mg L(-1) for DBPC, DBDS, and BTA, respectively. The Student's t values determined at 95% confidence level indicate that there is no significant difference between the experimental means obtained by this method and the standard method for each component. PMID- 22311821 TI - Laparoscopically assisted sacroperitoneal pull-through for high imperforate anus: a new technique. PMID- 22311823 TI - Magnetic bistability of isolated giant-spin centers in a diamagnetic crystalline matrix. AB - Polynuclear single-molecule magnets (SMMs) were diluted in a diamagnetic crystal lattice to afford arrays of independent and iso-oriented magnetic units. Crystalline solid solutions of an Fe(4) SMM and its Ga(4) analogue were prepared with no metal scrambling for Fe(4) molar fractions x down to 0.01. According to high-frequency EPR and magnetic measurements, the guest SMM species have the same total spin (S=5), anisotropy, and high-temperature spin dynamics found in the pure Fe(4) phase. However, suppression of intermolecular magnetic interactions affects magnetic relaxation at low temperature (40 mK), where quantum tunneling (QT) of the magnetization dominates. When a magnetic field is applied along the easy magnetic axis, both pure and diluted (x=0.01) phases display pronounced steps at evenly spaced field values in their hysteresis loops due to resonant QT. The pure Fe(4) phase exhibits additional steps which are firmly ascribed to two molecule QT transitions. Studies on the field-dependent relaxation rate showed that the zero-field resonance sharpens by a factor of five and shifts from about 8 mT to exactly zero field on dilution, in agreement with the calculated variation of dipolar interactions. The tunneling efficiency also changes significantly as a function of Fe(4) concentration: the zero-field resonance is significantly enhanced on dilution, while tunneling at +/-0.45 T becomes less efficient. These changes were rationalized on the basis of a dipolar shuffling mechanism and transverse dipolar fields, whose effect was analyzed by using a multispin model. Our findings directly prove the impact of intermolecular magnetic couplings on SMM behavior and disclose the magnetic response of truly isolated giant spins in a diamagnetic crystalline environment. PMID- 22311824 TI - Autonomous motivation: a predictor of treatment outcome in bulimia-spectrum eating disorders. AB - Individuals with eating disorders are said to be highly ambivalent towards change and thus have difficulty maintaining a commitment to, and motivation for, treatment. Self-Determination Theory postulates that autonomous motivation for therapy exists when individuals view their participation as freely chosen. OBJECTIVE: The present study was designed to ascertain whether or not autonomous motivation was associated with treatment response in individuals with bulimia spectrum eating disorders (BSED). METHOD: One hundred and fifty-five women with DSM-IV-TR BSED participated in multimodal group therapy and completed measures to assess motivation, eating and comorbid symptoms. RESULTS: Hierarchical multiple regression analyses demonstrated that higher levels of autonomous motivation at pretreatment predicted lower post-treatment scores on measures of eating preoccupations (shape, weight and eating concerns), binge eating, anxiety/depression, relationship to self and others and impulsivity. DISCUSSION: These results indicate that autonomous motivation may be an important predictor of outcome following treatment for BSED. PMID- 22311825 TI - Search engine processor: Filtering and organizing peptide spectrum matches. AB - The search engine processor (SEPro) is a tool for filtering, organizing, sharing, and displaying peptide spectrum matches. It employs a novel three-tier Bayesian approach that uses layers of spectrum, peptide, and protein logic to lead the data to converge to a single list of reliable protein identifications. SEPro is integrated into the PatternLab for proteomics environment, where an arsenal of tools for analyzing shotgun proteomic data is provided. By using the semi-labeled decoy approach for benchmarking, we show that SEPro significantly outperforms a commercially available competitor. PMID- 22311826 TI - Copper-catalyzed cross-coupling interrupted by an opportunistic Smiles rearrangement: an efficient domino approach to dibenzoxazepinones. PMID- 22311827 TI - Levels and types of alcohol biomarkers in DUI and clinic samples for estimating workplace alcohol problems. AB - Widespread concern about illicit drugs as an aspect of workplace performance potentially diminishes attention on employee alcohol use. Alcohol is the dominant drug contributing to poor job performance; it also accounts for a third of the worldwide public health burden. Evidence from public roadways--a workplace for many--provides an example of work-related risk exposure and performance lapses. In most developed countries, alcohol is involved in 20-35% of fatal crashes; drugs other than alcohol are less prominently involved in fatalities. Alcohol biomarkers can improve detection by extending the timeframe for estimating problematic exposure levels and thereby provide better information for managers. But what levels and which markers are right for the workplace? In this paper, an established high-sensitivity proxy for alcohol-driving risk proclivity is used: an average eight months of failed blood alcohol concentration (BAC) breath tests from alcohol ignition interlock devices. Higher BAC test fail rates are known to presage higher rates of future impaired-driving convictions (driving under the influence; DUI). Drivers in alcohol interlock programmes log 5-7 daily BAC tests; in 12 months, this yields thousands of samples. Also, higher programme entry levels of alcohol biomarkers predict a higher likelihood of failed interlock BAC tests during subsequent months. This paper summarizes the potential of selected biomarkers for workplace screening. Markers include phosphatidylethanol (PEth), percent carbohydrate deficient transferrin (%CDT), gammaglutamyltransferase (GGT), gamma %CDT (gamma%CDT), and ethylglucuronide (EtG) in hair. Clinical cut off levels and median/mean levels of these markers in abstinent people, the general population, DUI drivers, and rehabilitation clinics are summarized for context. PMID- 22311828 TI - Electron transport through single pi-conjugated molecules bridging between metal electrodes. AB - Understanding electron transport through a single molecule bridging between metal electrodes is a central issue in the field of molecular electronics. This review covers the fabrication and electron-transport properties of single pi-conjugated molecule junctions, which include benzene, fullerene, and pi-stacked molecules. The metal/molecule interface plays a decisive role in determining the stability and conductivity of single-molecule junctions. The effect of the metal-molecule contact on the conductance of the single pi-conjugated molecule junction is reviewed. The characterization of the single benzene molecule junction is also discussed using inelastic electron tunneling spectroscopy and shot noise. Finally, electron transport through the pi-stacked system using pi-stacked aromatic molecules enclosed within self-assembled coordination cages is reviewed. The electron transport in the pi-stacked systems is found to be efficient at the single-molecule level, thus providing insight into the design of conductive materials. PMID- 22311829 TI - Does preoperative therapy optimize outcomes in patients with resectable pancreatic cancer? AB - The objective of this study was to compare survival between all patients with radiographically resectable adenocarcinoma of the proximal pancreas who underwent preoperative chemoradiation therapy (PRE-OP CRT) or surgical exploration first (SURGERY) with "intention to resect." Pancreatic cancer patients who undergo resection after PREOP CRT live longer than patients who undergo resection without PREOP CRT, a difference that may be attributable to patient selection. We retrospectively identified 236 patients with pancreatic head adenocarcinoma seen between 1999 and 2007 with sufficient data to be confirmed medically and radiographically resectable. The outcomes of 144 patients who underwent PREOP CRT were compared to those of 92 patients who proceeded straight to SURGERY. The groups were similar in age and gender. Tumors were slightly larger in the PREOP CRT group (mean 2.5 cm vs. 2.1 cm, P < 0.01), and there were trends toward more venous abutment (54% vs. 39%, P = 0.06) and a higher Charlson comorbidity index (P = 0.1). In the PREOP CRT group, 76 patients (53%) underwent resection, 28 (19%) had metastatic and 17 (12%) locally unresectable disease after PREOP CRT, and 23 (16%) were not explored due to performance status or loss to follow-up. In the SURGERY group, 68 patients (74%) underwent resection. Sixteen patients (17%) had metastatic and eight patients (9%) locally unresectable disease at exploration. In patients who underwent resection, the PREOP CRT group had smaller pathologic tumor size and lower incidence of positive lymph nodes than the SURGERY group but no difference in positive margins or need for vascular resection. Median overall survival (OS) in patients undergoing resection was 27 months in the PREOP CRT group and 17 months in the SURGERY group (P = 0.04). Median OS in all patients treated with PREOP CRT or surgically explored with intention to resect was 15 and 13 months, respectively, with superimposable survival curves. Despite a lower resection rate, the PREOP CRT group as a whole had a similar OS to the SURGERY group as a whole. For patients who underwent resection, those in the PREOP CRT had longer survival than those in the SURGERY group, suggesting that PREOP CRT allows better patient selection for resection. PREOP CRT should be considered an acceptable alternative for most patients with resectable pancreatic cancer. PMID- 22311830 TI - Intermolecular communication on a liposomal membrane: enzymatic amplification of a photonic signal with a gemini peptide lipid as a membrane-bound artificial receptor. AB - A supramolecular system that can activate an enzyme through photo-isomerization was constructed by using a liposomal membrane scaffold. The design of the system was inspired by natural signal transduction systems, in which enzymes amplify external signals to control signal transduction pathways. The liposomal membrane, which provided a scaffold for the system, was prepared by self-assembly of a photoresponsive receptor and a cationic synthetic lipid. NADH-dependent L-lactate dehydrogenase, the signal amplifier, was immobilized on the liposomal surface by electrostatic interactions. Recognition of photonic signals by the membrane-bound receptor induced photo-isomerization, which significantly altered the receptor's metal-binding affinity. The response to the photonic signal was transmitted to the enzyme by Cu(2+) ions. The enzyme amplified the chemical information through a catalytic reaction to generate the intended output signal. PMID- 22311831 TI - Viability of human mesenchymal stem cells seeded on crosslinked entropy-elastic gelatin-based hydrogels. AB - Biomimetic polymer network systems with tailorable properties based on biopolymers represent a class of degradable hydrogels that provides sequences for protein adsorption and cell adhesion. Such materials show potential for in vitro MSC proliferation as well as in vivo applications and were obtained by crosslinking different concentrations of gelatin using varying amounts of ethyl lysine diisocyanate in the presence of a surfactant in pH 7.4 PBS solution. Material extracts, which were tested for cytotoxic effects using L929 mouse fibroblasts, were non-toxic. The hydrogels were seeded with human bone marrow derived MSCs and supported viable MSCs for the incubation time of 9 d. Preadsorption of fibronectin on materials improved this biofunctionality. PMID- 22311832 TI - Nanoconfinement effects: glucose oxidase reaction kinetics in nanofluidics. AB - Size-tunable nanofluidic devices coupled to an electrochemical detector have been designed and then used to study glucose oxidase (GOx) reaction kinetics confined in nanospaces. The devices are fabricated via a photochemical decomposition reaction, which forms nanochannels covered with carboxyl groups. The generated carboxyl groups enable us to chemically pattern biological molecules on the polymer surfaces via covalent bonding. With this approach, the activity of the immobilized biological molecules confined in nanospaces with different sizes has been investigated. GOx species are chemically immobilized on the surface of the nanochannels, catalyzing the oxidation of substrate glucose as it flows through the channels. The enzyme reaction product, hydrogen peroxide, passing through the nanochannels, reaches an electrochemical detector, giving rise to an increase in anodic current. This steady-state electrochemical current, which responds to various glucose concentrations, can be used to evaluate the GOx activity under confinement conditions. The results show significant nanoconfinement effects that are dependent on the channel size where the reaction occurs, demonstrating the importance of spatial confinement on the GOx reaction kinetics. The present approach provides an effective method for the study of enzyme activity and other bioassay systems, such as cell assays, drug discovery, and clinical diagnosis. PMID- 22311833 TI - Editorial. PMID- 22311834 TI - Comparison of traditional 2-dimensional endoscopic pituitary surgery with new 3 dimensional endoscopic technology: intraoperative and early postoperative factors. AB - BACKGROUND: Traditionally, endoscopic transsphenoidal pituitary surgery is performed using 2-dimensional (2D) endoscopes, which lack depth of field and contribute to image distortion. Recently, a new generation of 3D endoscopes has been introduced for improved endoscopic depth perception. Little data exist comparing surgical outcomes with 2D vs 3D endoscopic systems. This study examines perioperative and postoperative factors in patients undergoing pituitary surgery using 2D vs 3D endoscopes. The objective of this work was to determine the differences in perioperative and postoperative factors in patients undergoing pituitary surgery using 2D vs 3D endoscopy. METHODS: Retrospective chart review at a tertiary academic referral center. Statistical comparison was undertaken for perioperative (estimated blood loss, operative time) and postoperative factors (length of stay, complications, and readmission rate). RESULTS: A total of 58 patients underwent endoscopic pituitary surgery during the 24-month study period (22 functional, 36 nonfunctional lesions). The 2D endoscopic system was used for pituitary tumor resection in 32 patients (55%), and the 3D endoscopic system in 26 patients (45%). No significant difference existed between 2D and 3D endoscopic systems for operative time (p = 0.275) or estimated blood loss (p = 0.312). Additionally, no difference was found between groups for cerebrospinal fluid (CSF) leak rate (p = 0.581), postoperative endocrine complications (p = 0.081), length of hospital stay (p = 0.934), or hospital readmission rate (p = 1.0). CONCLUSION: 3D endoscopy affords the surgeon improved depth of field and stereoscopic vision. Our data demonstrate that 3D endoscopy does not result in significantly different perioperative or postoperative outcomes vs 2D endoscopic surgery. PMID- 22311835 TI - Endoscopic endonasal approaches to the cavernous sinus. AB - BACKGROUND: Surgical access to the cavernous sinus (CS) has proven a challenge for the skull base surgeon. Traditional approaches include the transcranial route, which broaches the lateral wall of the CS and has a high risk of cranial nerve weakness. A medial approach is more logical but the microscopic transsphenoidal approach has a restricted view. The endoscopic endonasal approach provides an alternative medial approach with improved visualization to that provided with the microscope. We describe our results using this approach for resection of CS tumors. METHODS: A retrospective chart review was performed of all patients treated surgically at a tertiary care referral center between January 2004 and February 2011 with a purely endoscopic endonasal approach to the CS. RESULTS: Out of 400 total endoscopic skull base cases, 41 (10.3%) involved the cavernous sinus. The most common approach was the transsphenoidal transsellar approach (31 patients, 75.6%). Other approaches included the tran-sethmoidal transsphenoidal parasellar (4 patients, 9.8%) and transmaxillary transpterygoidal (6 patients, 14.6%). The most common pathology was pituitary macroadenoma (24 patients, 58.5%). Gross total resection was achieved in 18 patients (43.9%). Cerebrospinal fluid (CSF) leak was not encountered in any patient postoperatively. Complications included 1 case of new postoperative VIth nerve palsy, 1 case of intraoperative hemorrhage, 2 cases of persistent diabetes insipidus, and 2 cases of sinusitis. CONCLUSION: The endoscopic endonasal approach is a safe and effective option for tumor resection in the CS using a medial to lateral route for selected cases. Morbidity is low and a variety of reconstructive options are available. PMID- 22311836 TI - Endoscopic verification of the sphenoid sinus. AB - BACKGROUND: Differentiating between posterior ethmoid and sphenoid sinuses can be difficult endoscopically. Anatomic relationships should guide surgery, irrespective of the ability to verify them with image guidance. The authors sought to verify an anatomic landmark found to be useful during endoscopic sinus surgery: the ability to see the sphenoid floor with a 0-degree nasal endoscope. METHODS: The angle formed by a nasal endoscope placed at the sphenoid ostium and the mucosa of the sphenoid floor was measured in 93 consecutive sphenoid sinuses radiologically. Angles of view of 3 common endoscopes were directly measured and compared to the radiologic measurements. RESULTS: The angle to the most inferior aerated portion of the sphenoid sinus averaged 113.6 degrees with a range of 77 to 145 degrees. The angle of view of the 3 endoscopes was found to be 38.1 degrees, 46.7 degrees, and 44.4 degrees. With these angles of view, the most inferior aerated portion of 100% of the radiologically assessed sinuses could not be seen with these endoscopes. CONCLUSION: Inability to see the mucosa of the floor of the sphenoid sinus with a 0-degree nasal endoscope appears to be a reliable finding. Individual variations that may affect this finding such as hypoplasia or severe mucosal edema should be identified preoperatively on imaging. In their absence, the inability to see the floor of an entered sinus with a 0-degree nasal endoscope provides another reliable clue to the position of the sphenoid sinus during endoscopic sinus surgery. PMID- 22311837 TI - The effect of low-fidelity endoscopic sinus surgery simulators on surgical skill. AB - BACKGROUND: Surgical training models are being increasingly used to provide an environment for surgical trainees to improve their skills without risk to patients. This study uses previously validated, inexpensive, low-fidelity training models to determine how pretraining affects endoscopic sinus surgery (ESS) skills. METHODS: Fourteen Otolaryngology residents were randomized to 1 of 2 groups that were stratified for training level. The first group took part in a pretraining session where they practiced on all 5 different modules whereas the second group did not receive any pretraining. The following day, all participants took part in a cadaveric ESS course. Participants were instructed to complete a set of tasks and their performances were videotaped. The videos were then evaluated using a Global Rating Scale (GRS) and a Task-Specific Checklist (TSC). The performances of those who trained using the models were compared to the performances of those who did not. RESULTS: The intervention (pretraining) group performed better than the nonintervention (no pretraining) group on the cadaveric ESS tasks (p < 0.05). As well, there was a statistical difference between the senior residents who had the pretraining with the simulator models performing better than those who did not. CONCLUSION: The modules appear to have made a positive impact on ESS skills. These low-cost, easily-constructed training modules have the potential to be integrated into Otolaryngology-Head and Neck Surgery resident training. Assessment of long-term training effects with a larger number of participants is planned for future studies. PMID- 22311838 TI - Perioperative care in functional endoscopic sinus surgery: a survey study. AB - BACKGROUND: Functional endoscopic sinus surgery (FESS) is largely viewed as the standard of care in the treatment of chronic rhinosinusitis (CRS) refractory to medical treatment. While there is an understanding regarding the importance of some form of routine postoperative FESS care, no consensus currently exists regarding what the specific management routine should include. The authors of this survey study did not intend to examine the efficacy of such treatment protocols, but rather to determine and report on the current practice patterns of perioperative FESS care among otolaryngologists. METHODS: This survey study was designed in accordance with and approved by our institutional review board. The online-based survey was designed using the online product SurveyMonkey(r). A total of 859 otolaryngologists were identified and email addresses were obtained from the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) website directory. Responses were collected anonymously. RESULTS: Our survey response rate was 32%. Multiple parameters of the otolaryngologists' perioperative care were collected. Among the data, some consistent patterns emerged: 93.2% of respondents use nasal saline irrigations postoperatively; 86.8% of otolaryngologists surveyed prescribe antibiotics in the immediate postoperative period; and office-based endoscopic sinus debridements are performed by a majority (87.9%) of those surveyed. CONCLUSION: This survey study demonstrates that current practices in perioperative FESS care can vary widely among otolaryngologists, and are not uniformly based on evidence-based outcomes research. Despite the lack of absolutes regarding the specific perioperative care in FESS, practice patterns emerge from the data regarding typical perioperative management among current otolaryngologists. PMID- 22311839 TI - Nationwide incidence of major complications in endoscopic sinus surgery. AB - BACKGROUND: Endoscopic sinus surgery (ESS) is one of the most commonly performed procedures in otolaryngology. Major complications are estimated to occur in 1-3% of cases, based on early studies with relatively small patient cohorts in academic institutions. The aim of this study was to update data regarding major complication rates associated with ESS by analyzing a large patient database. METHODS: Retrospective review of a nationwide database of patients who underwent ESS between 2003 and 2007. Major postoperative complications-cerebrospinal fluid (CSF) leak, orbital injury, and hemorrhage requiring blood transfusion-were identified by searching the database for related International Classification of Diseases, 9th edition (ICD-9) and Current Procedural Terminology (CPT) codes. Complication rates were examined and time to occurrence analyzed. Two-tailed test of proportions, global chi-square test, and logistical regression analysis were used for statistical comparison. RESULTS: A total of 62,823 patients who met rigorous inclusion criteria were included. The overall major complication rate was 1.00% (CSF leak 0.17%; orbital injury 0.07%; hemorrhage requiring transfusion 0.76%). CSF leak was less likely to occur in the pediatric population (p = 0.05), whereas orbital injury was more likely to occur in children (p < 0.001). Examination of the impact of image guidance (IGS) was limited by study design. CONCLUSION: The incidence of major complications associated with ESS appears to have decreased since early reports over 10 years ago. There may be different complication rates in the pediatric population. Study design limitations did not allow for comprehensive assessment of IGS in the development of these complications. These data help to educate otolaryngologists and patients about complication rates in ESS in a modern context. PMID- 22311840 TI - Back-and-forth endoscopic septoplasty: analysis of the technique and outcomes. AB - BACKGROUND: To describe our clinical experience in 218 consecutive patients undergoing endoscopic back-and-forth septoplasty (EBFS), examining surgical indications, technique, and follow-up. METHODS: From January 2005 to November 2008, 218 patients underwent EBFS at the Department of Otorhinolaryngology, San Raffaele Hospital, Milan, Italy. The indication for EBFS in this series was nasal airway obstruction (NAO). Patients were studied with nasal rigid endoscopy and in some cases computed tomography (CT) was used to exclude rhinosinusitis. The most common concomitant diagnoses included allergic rhinitis and turbinate hypertrophy. EBFS facilitates the interruption of perichondrial and periosteal bridges, which are more represented in the anterior portion of the septum between the caudal quadrangular cartilage and the vomeropremaxillary crest. Septal splints were positioned. No nasal packing was required. RESULTS: No cases required conversion to a traditional headlight approach, and no intraoperative complications were encountered. Intraoperative mucosal microlacerations occurred in 77.98% of cases; suturing was required in only 8.25% of cases. Of 218 patients, 74.77% experienced resolution of NAO, while 16.06% experienced only improvement; 9.17% noted the persistence of symptoms. Complications included transient dental pain/hypesthesia (6.88%), septal hematoma (5.04%), synechiae formation (2.29%), epistaxis (1.83%), septal perforation (1.83%), cheek swelling (0.45%), and septal abscess (0.45%). CONCLUSION: EBFS as a variation of endoscopic septoplasty (ES) represents a viable procedure with good outcomes and a low rate of complications. The technique allows lysis of tissue fibers while preserving the integrity of mucosa at the critical area using less force and reduces the probability of mucosal tears, based on embryologic knowledge of anatomical dissection. PMID- 22311841 TI - Oral antifungal therapy for Fusarium-associated chronic rhinosinusitis. AB - BACKGROUND: Fusarium is commonly reported as an organism found in fungus associated chronic rhinosinusitis (CRS) yet it is known to be resistant to commonly used antifungal therapies. The goals of this work are to report the incidence of Fusarium-associated CRS in fungal cultures and to describe the treatment experience with oral antifungal agent aimed at this problem. METHODS: Patients with sinus cultures obtained from 2005 through 2008 were retrospectively identified and their medical records were evaluated. Cultures were obtained in patients with recalcitrant rhinosinusitis when purulent discharge was observed. Patient response to the therapy was measured upon the basis of self reported symptom improvements and endoscopic examination. RESULTS: In this 4-year period 2,570 outpatient fungal cultures were obtained and 194 (7.5%) were positive for Fusarium. These 194 positive cultures appeared in 94 individuals. Thirty-four tested positive multiple times. Twenty-three (24.5%) had severe recalcitrant CRS poorly responsive to standard therapies warranting antifungal therapy aimed at Fusarium. Fifteen individuals were treated with voriconazole, 5 with posaconazole, and 3 with both at separate times. Endoscopic evidence of initial improvement on therapy was evident in 16 of 23 patients (69.6%). Of 18 patients who could comment on their experience with the antifungal treatments, nearly 90% of them reported substantial improvement with the therapy. Nine (9/23; 39.1%) were forced to discontinue oral antifungal therapy due to untoward effects. CONCLUSION: Fusarium appears in 7.55% of outpatient cultures of CRS. Of the patients testing positive for Fusarium, 25% received oral antifungal therapy. A positive response was seen in 16 of 23 (69.6%) while receiving other standard therapies. Since Fusarium is not routinely sensitive to commonly used antifungal agents, it warrants special attention. PMID- 22311842 TI - Allergic rhinitis, chronic rhinosinusitis, and symptom severity: a population based study. AB - BACKGROUND: Approximately 20% of the U.S. population suffers from allergic rhinitis (AR), and chronic rhinosinusitis (CRS) is estimated to affect 12.5% of the population. Frequently, many patients suffer from both disorders. In this study, we evaluated the relationship between AR and chronic rhinosinusitis as far as impact on nasal symptoms in a community-based case-control study of adult nonsmokers. METHODS: In Washington County, MD, 200 subjects were recruited and interviewed from the same community. Subjects were divided into 4 study groups: AR without CRS, CRS without AR, AR with CRS, and a control group without AR or CRS. A validated questionnaire was used to assess upper respiratory symptoms, and disease-specific quality of life. RESULTS: Upper respiratory symptoms were significantly more severe for the affected subjects when compared to controls. Symptom severity was greatest for the CRS groups with or without AR, followed by AR without CRS, and controls least symptomatic. Subjects with AR plus CRS were most likely to have had previous nasal surgery, and use nasal decongestants when compared to the other groups. CONCLUSION: While both AR and CRS are common in the United States, it appears that patients who suffer from both disorders have more severe symptoms and are more likely to have undergone nasal surgery than if they have only 1 of these disease states. PMID- 22311843 TI - Quantitative analysis of in vivo mucosal bacterial biofilms. AB - BACKGROUND: Quantitative assays of mucosal biofilms on ex vivo samples are challenging using the currently applied specialized microscopic techniques to identify them. The COMSTAT2 computer program has been applied to in vitro biofilm models for quantifying biofilm structures seen on confocal scanning laser microscopy (CSLM). The aim of this study was to quantify Staphylococcus aureus (S. aureus) biofilms seen via CSLM on ex situ samples of sinonasal mucosa, using the COMSTAT2 program. METHODS: S. aureus biofilms were grown in frontal sinuses of 4 merino sheep as per a previously standardized sheep sinusitis model for biofilms. Two sinonasal mucosal samples, 10 mm * 10 mm in size, from each of the 2 sinuses of the 4 sheep were analyzed for biofilm presence with Baclight stain and CSLM. Two random image stacks of mucosa with S. aureus biofilm were recorded from each sample, and analyzed using COMSTAT2 software that translates image stacks into a simplified 3-dimensional matrix of biofilm mass by eliminating surrounding host tissue. Three independent observers analyzed images using COMSTAT2 and 3 repeated rounds of analyses were done to calculate biofilm biomass. RESULTS: The COMSTAT2 application uses an observer-dependent threshold setting to translate CSLM biofilm images into a simplified 3-dimensional output for quantitative analysis. Intraclass correlation coefficient (ICC) between thresholds set by the 3 observers for each image stacks was 0.59 (p = 0.0003). Threshold values set at different points of time by a single observer also showed significant correlation as seen by ICC of 0.80 (p < 0.001). CONCLUSION: COMSTAT2 can be applied to quantify and study the complex 3-dimensional biofilm structures that are recorded via CSLM on mucosal tissue like the sinonasal mucosa. PMID- 22311844 TI - Mucosal brush biopsy testing of the inferior turbinate to detect local, antigen specific immunoglobulin E. AB - BACKGROUND: This study investigated the ability of mucosal brush biopsy testing (MBBT) from the inferior turbinate to detect local, antigen-specific immunoglobulin E (IgE) in patients with allergic rhinitis, and these results were then compared to skin prick testing (SPT). METHODS: A standard cytology brush was used to harvest epithelial cells from the inferior turbinates of 20 patients who tested positive to 2 or more airborne antigens out of a panel of 9 on SPT (N = 20). These cells were lysed and the resulting solution was tested for total and antigen-specific IgE using immunofluorescence. RESULTS: Antigen-specific IgE for at least 1 antigen was detected in 15 (75%) patients on MBBT. A statistically significant association overall between the results of MBBT and SPT was present (p = 0.01), but no significant associations were seen when examining individual antigens. Patients with positive tests on MBBT had higher amounts of IgE and total protein in biopsy samples than patients without positive tests on MBBT. The mean wheal diameter in tests that were positive on MBBT were significantly larger than the mean wheal diameter in tests that were negative on MBBT (p < .0001). Eight tests were positive on MBBT that were negative on SPT in the same patients. CONCLUSION: This study demonstrates for the first time that antigen-specific IgE can be detected using MBBT in the sinonasal cavity. MBBT is more likely to be positive in higher SPT grades and in biopsy samples with more protein present. MBBT is also able to detect local IgE that is not detected on SPT. PMID- 22311845 TI - Keratinocyte chemoattractant (interleukin-8) regulation of sinonasal cilia function in a murine model. AB - BACKGROUND: Chronic rhinosinusitis is a multifactorial disease characterized by a local inflammatory response and impaired mucociliary clearance. Our prior work suggests that nonpolypoid inflammation can blunt ciliary dynamics. Thus, we set out to determine whether exogenously applied recombinant keratinocyte chemoattractant (KC), mouse homologue of interleukin-8 (IL-8), modulates ciliary function. METHODS: Murine primary sinonasal cultures were established in an air liquid interface. Exogenous KC was administered to apical and basal surfaces at 500 pg/mL (n = 6) or 5 ng/mL (n = 3). Basal and stimulated cilia beat frequency (CBF) was recorded at 6, 12, 24, and 48 hours after exposure. Control groups were treated with buffered saline solution (n = 6). Cilia were mechanically stimulated with bursts of pressurized air (55 mmHg). CBF after prolonged KC exposure (96 hours) was also measured. RESULTS: KC-treated cultures had significantly increased basal CBF at 24 hours and 48 hours. KC (500 pg/mL) yielded a 41.6% +/- 9.5 increase in basal CBF (p < 0.001) at 24 hours, which persisted at 48 hours, 35.8% +/- 10.2 (p < 0.05), while high-concentration KC (5 ng/mL) yielded a 50.2% +/- 6.6 (p < 0.01) increase in basal CBF at 24 hours, which declined to 15.2% +/- 5.2 (p < 0.01) at 48 hours. After 48 hours, the KC group demonstrated decreased response to mechanical stimulus vs control (500 pg/mL: p < 0.01, 5 ng/mL: p <= 0.04). With prolonged KC exposure (500 pg/mL) CBF declined: -25.5% +/- 6.9 (p < .001) at 72 hours, and -19.6% +/- 5.4 (p < 0.01) at 96 hours. CONCLUSION: Our results demonstrate modulation of cilia function of murine sinonasal epithelial cells by the inflammatory cytokine KC, which acutely increases basal CBF while decreasing the response of cilia to mechanical stimulation. Prolonged KC exposure decreases basal CBF. PMID- 22311846 TI - Epigenetics of chronic rhinosinusitis and the role of the eosinophil. AB - BACKGROUND: One theory for the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) involves aberration in the expression of genes that maintain the sinonasal innate immune system. We propose that the alteration in gene expression seen in CRSwNP is a result of oxidative byproducts of eosinophils. Activated eosinophils and neutrophils may lead to the production of hypobromous acid (HOBr) and hypochlorous acid (HOCL) and the posttranslational modification products 5 bromocytosine (5BrC) and 5-chlorocytosine (5ClC), respectively. 5BrC and 5ClC may cause aberrant methylation of cytosine during DNA replication and mimic the endogenous methylation signal associated with gene silencing. We propose to use gas chromatography-mass spectrometry (GC-MS) to identify the presence of 5BrC and 5ClC in CRSwNP patients. METHODS: Patients with CRSwNP undergoing endoscopic sinus surgery were prospectively recruited into this study. Using GC-MS, tissue specimens were analyzed for the presence of 5BrC, 5ClC, and methylated cytosine. RESULTS: Tissue specimens from 14 patients with CRSwNP and 3 normal controls were processed using GC-MS. CRSwNP specimens demonstrate elevated levels of 5BrC and 5ClC compared to normal controls. CONCLUSION: Eosinophils, which are predominantly found in CRSwNP, may lead to DNA modification and gene silencing via 5BrC and aberrant methylation patterns and may help explain the pathogenesis of CRSwNP. PMID- 22311847 TI - Does food intolerance play a role in recurrent respiratory papillomatosis? AB - BACKGROUND: The purpose of this study is to evaluate the potential role of food intolerances in the management of recurrent respiratory papillomatosis (RRP). METHODS: This is a retrospective case review of 4 pediatric patients with RRP. All of the patients, cared for by the primary author between 2005 and 2010, were managed using microdebrider resection, intralesional injection of cidofovir, and required multiple surgeries. Skin prick test (SPT) and/or radioallergosorbent test (RAST) were obtained for 2 patients. Oral food challenge was utilized in all 4 patients. RESULTS: Standard SPT and RAST did not identify any immunoglobulin E (IgE)-based allergens. A detailed medical history followed by an oral food challenge was successful at identifying food intolerances in all 4 patients. When specific food elimination was implemented in these patients' treatments in addition to microdebrider resection and cidofovir injection, statistically significant long-term remissions were achieved. CONCLUSION: Food intolerance and its impact on RRP and immune dysfunction deserve further investigation and may benefit some patients with RRP. PMID- 22311848 TI - Case report of orbital violation with placement of ethmoid drug-eluting stent. AB - BACKGROUND: Delivery of topical therapy is a mainstay in the treatment of chronic rhinosinusitis (CRS). Ethmoid sinus stenting has recently been introduced as a minimally invasive mechanism to deliver medication. We review available literature on ethmoid stenting and present a case report involving orbital violation and a fixed, dilated pupil. METHODS: Case report and literature review. RESULTS: A 37 year-old female underwent endoscopic placement of bilateral ethmoid sinus drug-eluting stents for CRS at an outside facility. Postoperatively she complained of right-sided ocular pain and pressure. She was seen in the emergency setting on post-operative day (POD) 2 and had a dilated right pupil. A computed tomography (CT) scan was performed and read as normal. The left stent was removed successfully on POD 19; the right could not be removed in the outpatient setting secondary to pain. The patient was transferred to our facility on POD 21. The CT from POD 2 was reviewed and demonstrated violation of the lamina papyracea and orbit with the stent abutting the lateral orbital wall. On POD 24, the patient underwent medial orbital decompression and successful stent removal but continues to have a dilated pupil in the affected eye. CONCLUSION: This is the first reported case of orbital violation with placement of an ethmoid drug-eluting stent. The literature shows feasibility in cadaveric studies but the practitioner must be diligent in placement. Ethmoid sinus stenting is an option for topical treatment of ethmoid sinusitis but practitioners must be cognizant of potential risks when counseling patients. PMID- 22311849 TI - Coenzyme Q10 concentration in plasma and blood cells of juvenile patients hospitalized for anorexia nervosa. AB - The antioxidant status of coenzyme Q10 (CoQ10) was investigated in plasma, erythrocytes, and platelets of juvenile patients with anorexia nervosa. Blood for analysis of the CoQ10 status was taken from 16 juvenile patients suffering from anorexia nervosa (restricting form) at the time point of admission to the hospital and at discharge after about 12 weeks. Plasma and blood cells isolated by a density gradient were stored at -84 degrees C until analysis. CoQ10 concentration and redox status were measured by high pressure liquid chromatography with electrochemical detection and internal standardization. The improvement of physical health during the hospital refeeding process was followed up by the body mass index (BMI). The antioxidant status of plasma CoQ10 in juvenile patients suffering from anorexia nervosa indicated no abnormalities in comparison to healthy controls. However, the decreased concentration of CoQ10 observed in platelets at the time point of hospital admission may represent mitochondrial CoQ10 depletion. This initial deficit improved during the hospital refeeding process. The platelet CoQ10 concentration showed a positive correlation to the BMI of the patients. PMID- 22311850 TI - Coordination environment of highly concentrated solutions of Cu(II) in ionic liquids through a multidisciplinary approach. AB - The coordination environment around Cu(II) in highly concentrated solutions of copper(II) salts (CuCl(2) and Cu(Tf(2)N)(2)) in two pure ionic liquids bearing the same anion, namely, 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([bmim][Tf(2)N]) and 1-butyl-3 methylimidazolium chloride ([bmim]Cl), is investigated by X-ray photoelectron spectroscopy (XPS), UV/Vis spectroscopy, EPR spectroscopy and DFT calculations. Moreover, the electrochemical behavior of these mixtures is studied. Whereas reversible reduction of Cu(II) to copper metal can be observed in the 1:1 [bmim][Tf(2)N]:Cu(Tf(2)N)(2) solution, 2:1 and 1:1 [bmim]Cl:CuCl(2) mixtures showed one-electron reduction of Cu(II) to Cu(I) with formation of a permanent deposit of CuCl. XPS, UV/Vis and EPR spectra as well as DFT calculations suggest the formation in [bmim]Cl of dynamic coordination complexes arising from the interaction between CuCl(2) and [bmim](+)Cl(-). The two long-lived situations are probably trigonal and deformed tetrahedral copper(II) chloride coordination complexes ([CuCl(3)](-) and [CuCl(4)](2-), respectively). PMID- 22311851 TI - Incorporation of pulse flours of different particle size in relation to pita bread quality. AB - BACKGROUND: To increase pulse consumption, pita bread was fortified with pulse flours milled from green lentils, navy beans and pinto beans, which were ground to produce fine and coarse flours. Pita breads were prepared using composite flours containing pulse flours (25, 50, 75%) and wheat flour or 100% pulse flours and adjusting the amount of water required for mixing based on farinograph water absorption. Pita bread quality was evaluated according to diameter, pocket height, specific loaf volume, texture and crust colour. RESULTS: Blends made from pulse flours with coarse particle size showed higher rates of water absorption. All composite flours and 100% pulse flours produced pitas with pockets, confirming their suitability for this product. Crust colour of pitas was affected less by navy bean flour than by lentil flour. Pita breads made with pinto bean flour were superior in texture. Overall, navy and pinto bean flours appeared more suitable for pita bread. Flours with coarse particle sizes produced pitas with better colour and texture. Sensory parameters of pitas containing 25% coarse pinto or navy bean flour were as good as or better than those from the wheat control. CONCLUSION: Acceptable pita breads can be made using pulse flours, although the substitution level is limited to 25%. PMID- 22311852 TI - From coronary care unit to acute cardiac care unit: the evolving role of specialist cardiac care. PMID- 22311853 TI - Cardiac involvement in muscular dystrophy: advances in diagnosis and therapy. PMID- 22311855 TI - Asymmetric focal pericardial thickening causing physiologically significant constrictive pericarditis. AB - A 34-year-old woman presented with refractory ascites and edema. Echocardiography revealed normal left ventricular function with a restrictive diastolic filling pattern. Tissue Doppler velocities of the mitral annulus were normal. Cardiac magnetic resonance imaging (MRI) revealed a focal region of pericardial thickening anterior to the right ventricle and normal thickness pericardium in the other segments. However, abnormal delayed enhancement MRI (consistent with inflammation) was present in both the thickened and the normal pericardial segments. Invasive hemodynamics confirmed constrictive physiology and the patient underwent successful pericardiectomy. This case highlights the utility of multimodality imaging in the diagnosis of constrictive pericarditis and the underappreciated fact that the pericardium need not be globally thickened to cause hemodynamically significant constrictive physiology. PMID- 22311854 TI - Transgene regulation in plants by alternative splicing of a suicide exon. AB - Compared to transcriptional activation, other mechanisms of gene regulation have not been widely exploited for the control of transgenes. One barrier to the general use and application of alternative splicing is that splicing-regulated transgenes have not been shown to be reliably and simply designed. Here, we demonstrate that a cassette bearing a suicide exon can be inserted into a variety of open reading frames (ORFs), generating transgenes whose expression is activated by exon skipping in response to a specific protein inducer. The surprisingly minimal sequence requirements for the maintenance of splicing fidelity and regulation indicate that this splicing cassette can be used to regulate any ORF containing one of the amino acids Glu, Gln or Lys. Furthermore, a single copy of the splicing cassette was optimized by rational design to confer robust gene activation with no background expression in plants. Thus, conditional splicing has the potential to be generally useful for transgene regulation. PMID- 22311856 TI - Effect of fruit load on maturity and carotenoid content of clementine (Citrus clementina Hort. ex Tan.) fruits. AB - BACKGROUND: Citrus fruits contain many secondary metabolites displaying valuable health properties. There is a lot of interest in enhancing citrus quality traits, especially carotenoid contents, by agronomic approaches. In this study the influence of carbohydrate availability on maturity and quality criteria was investigated in clementine fruits during ripening. Fruiting branches were girdled and defoliated after fruit set to obtain three levels of fruit load: high (five leaves per fruit), medium (15) and low (30). RESULTS: Considering the soluble solid content/titratable acidity (SSC/TA) ratio, it was found that fruits of the high and medium fruit load treatments reached maturity 1.5 months later than fruits of the control. At the time of maturity the SSC/TA ratio of fruits of all treatments was about 13.6. At harvest, fruits were 23% smaller and total sugar concentration of the endocarp was 12.6% lower in the high fruit load treatment than in the control. In contrast, the concentrations of organic acids and total carotenoids were 55.4 and 93.0% higher respectively. Total carotenoids were not positively correlated with either soluble sugars or total carbohydrates. CONCLUSION: Taken together, the results do not support the common view that carbohydrate availability directly determines carotenoid synthesis by influencing precursor availability. PMID- 22311857 TI - Is there an optimal pH for culture media used in clinical IVF? AB - BACKGROUND: Reducing environmental stress imposed upon gametes and embryos in the IVF laboratory is crucial in optimizing culture conditions and development. One environmental parameter of particular importance is external pH (pHe) of culture media. An optimal pHe has not been identified. METHODS: Electronic searches were performed using keywords focused on pH and the embryo using PUBMED through August 2011, with no limits placed on a beginning time. Examples of keywords include CO(2), bicarbonate and hydrogen ion. Relevant papers were then examined to obtain additional publications. RESULTS: Determining optimal pHe is problematic due to difficulty in isolating pHe from other variables, such as CO(2) and bicarbonate. Various commercial media companies recommend differing pHe ranges, most within the range of 7.2-7.4, with some companies recommending altering pHe based on the gamete or stage of the embryo. However, changing pHe during culture has not been experimentally shown to improve outcomes. Further complicating attempts to define an optimal pHe is that media components can impact intracellular pH (pHi). As a result, media with different concentrations of substances, such as lactate or amino acids, may have different pHi, despite being in the same pHe. CONCLUSIONS: Due to the plasticity of embryos, a range of pHe's can support development, and defining an optimal pHe is difficult. It is unclear whether there is any benefit in changing pHe at various steps during IVF. The ideal pHe will likely vary from media to media and, until comparative studies have been performed isolating pHe, adherence to manufacturer recommendations and maintenance of a small acceptable pHe range are advisable. PMID- 22311858 TI - Endothelin receptor antagonists: a place in the management of essential hypertension? PMID- 22311859 TI - Tocopherols in rose hips (Rosa spp.) during ripening. AB - BACKGROUND: Rose hips are used as a food ingredient and in health products. They are rich in various bioactive compounds such as carotenoids and vitamin C, but data on their vitamin E content (tocopherols and tocotrienols) are limited. In this study, four different species of Rosa were analysed for tocopherol and tocotrienol content during ripening in three different years. RESULTS: Only alpha and gamma-tocopherol were found in the fleshy parts of the rose hips, and the tocopherol content and vitamin E activity varied depending on date of harvesting, species and year. The amount of vitamin E activity differed between species of Rosa and years, whereas the changes during ripening were relatively small. CONCLUSION: The choice of species must be considered if tocopherol content is to be optimised when rose hips are used as a food ingredient. PMID- 22311860 TI - Long-term results of cephalad arteries percutanoeus transluminal angioplasty with stent implantation (The CAPTAS registry). AB - INTRODUCTION: Carotid artery stenting (CAS) has become an alternative to carotid endarterectomy. Moreover, percutaneous transluminal angioplasty (PTA) allows other cephalad arteries revascularization. The aim of this study was to evaluate late outcomes of cephalad arteries PTA. METHODS: This is an international multicenter registry of 434 consecutive patients in which 497 PTAs were performed. Patients with symptomatic >50% stenosis or asymptomatic >70% stenosis were enrolled. Stenting of 577 internal carotid arteries (ICA) and 13 common carotid arteries was performed, 20.7% procedures were complex in which bilateral carotid stenoses or carotid and vertebral arteries stenoses were revascularized at one stage. In 15.9% patients, one-stage coronary intervention was carried out. Distal protection devices were used in 69.6% of cases. PTAs were divided into high (n = 330) and low (n = 167) risk of major adverse coronary and cerebral events (MACCE). RESULTS: At 30 days, there were 15 (3.5%) cases of MACCE [0.9% deaths, 2.1% strokes, and 0.9% myocardial infarction (MI)]. TIAs were observed in 15 (3.9%) patients. There was no significant difference in stroke incidence between procedures with or without neuroprotection (1.8 vs. 3%; P = 0.66) as well as in MACCE occurrence between high and low-risk groups (4.3 vs. 2%; P = 0.34). Bilateral stenoses increased while hypertension decreased the risk of MACCE. Left ICA lesions increased the risk of cerebrovascular accidents (CVA). At 4 years (1 11 years), the mortality rate was 11.5%, 6% of patients had stroke, and 3% MIs. Restenosis occurred in 3%. There was a trend toward higher mortality rate (13.3 vs. 6.9%; P = 0.07) and MACCE risk in high-risk group (23.5 vs.14.7% P = 0.06). Age > 65 y.o. and stent length < 24 mm increased, while the statin therapy on admission decreased the risk of long-term death. Structural valve disease and stent length <30 mm increased the risk of MACCE, while implantation of Acculink stent decreased the risk of CVA. CONCLUSIONS: CAS is safe and successful procedure with low early and long-term adverse events. Special attention should be put on patients with bilateral and left ICA stenoses. If possible, longer stents should be applied. PMID- 22311861 TI - A fast O(N) multiresolution polygonal approximation algorithm for GPS trajectory simplification. AB - Recent advances in geopositioning mobile phones have made it possible for users to collect a large number of GPS trajectories by recording their location information. However, these mobile phones with built-in GPS devices usually record far more data than needed, which brings about both heavy data storage and a computationally expensive burden in the rendering process for a Web browser. To address this practical problem, we present a fast polygonal approximation algorithm in 2-D space for the GPS trajectory simplification under the so-called integral square synchronous distance error criterion in a linear time complexity. The underlying algorithm is designed and implemented using a bottom-up multiresolution method, where the input of polygonal approximation in the coarser resolution is the polygonal curve achieved in the finer resolution. For each resolution (map scale), priority-queue structure is exploited in graph construction to construct the initialized approximated curve. Once the polygonal curve is initialized, two fine-tune algorithms are employed in order to achieve the desirable quality level. Experimental results validated that the proposed algorithm is fast and achieves a better approximation result than the existing competitive methods. PMID- 22311862 TI - Medical image segmentation by combining graph cuts and oriented active appearance models. AB - In this paper, we propose a novel method based on a strategic combination of the active appearance model (AAM), live wire (LW), and graph cuts (GCs) for abdominal 3-D organ segmentation. The proposed method consists of three main parts: model building, object recognition, and delineation. In the model building part, we construct the AAM and train the LW cost function and GC parameters. In the recognition part, a novel algorithm is proposed for improving the conventional AAM matching method, which effectively combines the AAM and LW methods, resulting in the oriented AAM (OAAM). A multiobject strategy is utilized to help in object initialization. We employ a pseudo-3-D initialization strategy and segment the organs slice by slice via a multiobject OAAM method. For the object delineation part, a 3-D shape-constrained GC method is proposed. The object shape generated from the initialization step is integrated into the GC cost computation, and an iterative GC-OAAM method is used for object delineation. The proposed method was tested in segmenting the liver, kidneys, and spleen on a clinical CT data set and also on the MICCAI 2007 Grand Challenge liver data set. The results show the following: 1) The overall segmentation accuracy of true positive volume fraction TPVF > 94.3% and false positive volume fraction can be achieved; 2) the initialization performance can be improved by combining the AAM and LW; 3) the multiobject strategy greatly facilitates initialization; 4) compared with the traditional 3-D AAM method, the pseudo-3-D OAAM method achieves comparable performance while running 12 times faster; and 5) the performance of the proposed method is comparable to state-of-the-art liver segmentation algorithm. The executable version of the 3-D shape-constrained GC method with a user interface can be downloaded from http://xinjianchen.wordpress.com/research/. PMID- 22311863 TI - Impact of the lips for biometrics. AB - In this paper, the impact of the lips for identity recognition is investigated. In fact, it is a challenging issue for identity recognition solely by the lips. In the first stage of the proposed system, a fast box filtering is proposed to generate a noise-free source with high processing efficiency. Afterward, five various mouth corners are detected through the proposed system, in which it is also able to resist shadow, beard, and rotation problems. For the feature extraction, two geometric ratios and ten parabolic-related parameters are adopted for further recognition through the support vector machine. Experimental results demonstrate that, when the number of subjects is fewer or equal to 29, the correct accept rate (CAR) is greater than 98%, and the false accept rate (FAR) is smaller than 0.066%. (CAR > 95.02%, FAR < 0.095% # Subjects <= 57). Moreover, the processing speed of the overall system achieves 34.43 frames per second, which meets the real-time requirement. Thus, the proposed system can be an effective candidate for facial biometrics applications when other facial organs are covered or when it is applied for an access control system. PMID- 22311864 TI - A hierarchical gene regulatory network for adaptive multirobot pattern formation. AB - Most existing multirobot systems for pattern formation rely on a predefined pattern, which is impractical for dynamic environments where the pattern to be formed should be able to change as the environment changes. In addition, adaptation to environmental changes should be realized based only on local perception of the robots. In this paper, we propose a hierarchical gene regulatory network (H-GRN) for adaptive multirobot pattern generation and formation in changing environments. The proposed model is a two-layer gene regulatory network (GRN), where the first layer is responsible for adaptive pattern generation for the given environment, while the second layer is a decentralized control mechanism that drives the robots onto the pattern generated by the first layer. An evolutionary algorithm is adopted to evolve the parameters of the GRN subnetwork in layer 1 for optimizing the generated pattern. The parameters of the GRN in layer 2 are also optimized to improve the convergence performance. Simulation results demonstrate that the H-GRN is effective in forming the desired pattern in a changing environment. Robustness of the H-GRN to robot failure is also examined. A proof-of-concept experiment using e-puck robots confirms the feasibility and effectiveness of the proposed model. PMID- 22311865 TI - Cooperative output regulation with application to multi-agent consensus under switching network. AB - In this paper, we consider the cooperative output regulation of linear multi agent systems under switching network. The problem can be viewed as a generalization of the leader-following consensus problem of multi-agent systems. Due to the limited information exchanges of different subsystems, the problem cannot be solved by the decentralized approach and is not allowed to be solved by the centralized control. By devising a distributed observer network, we can solve the problem by both dynamic state feedback control and dynamic measurement output feedback control. As an application of our main result, we show that a special case of our results leads to the solution of the leader-following consensus problem of linear multi-agent systems. PMID- 22311866 TI - Content-based microscopic image retrieval system for multi-image queries. AB - In this paper, we describe the design and development of a multitiered content based image retrieval (CBIR) system for microscopic images utilizing a reference database that contains images of more than one disease. The proposed CBIR system uses a multitiered approach to classify and retrieve microscopic images involving their specific subtypes, which are mostly difficult to discriminate and classify. This system enables both multi-image query and slide-level image retrieval in order to protect the semantic consistency among the retrieved images. New weighting terms, inspired from information retrieval theory, are defined for multiple-image query and retrieval. The performance of the system was tested on a dataset including 1666 imaged high power fields extracted from 57 follicular lymphoma (FL) tissue slides with three subtypes and 44 neuroblastoma (NB) tissue slides with four subtypes. Each slide is semantically annotated according to their subtypes by expert pathologists. By using leave-one-slide out testing scheme, the multi-image query algorithm with the proposed weighting strategy achieves about 93% and 86% of average classification accuracy at the first rank retrieval, outperforming the image-level retrieval accuracy by about 38 and 26 percentage points, for FL and NB diseases, respectively. PMID- 22311867 TI - Does the site of bleeding matter? A stratified analysis on location of TIMI graded bleedings and their impact on 12-month outcome in patients with ST-segment elevation myocardial infarction. AB - AIMS: While bleeding in patients with STEMI undergoing primary percutaneous coronary intervention (pPCI) is known to be associated with poor outcomes, the differential prognostic impact of access-site related versus non access-site related bleedings is unknown. We aimed to assess the relative impact of access site related bleeding, as compared to non access-site related, on 12-month clinical outcome in patients undergoing intervention for STEMI. METHODS AND RESULTS: Thirty-day bleeding endpoints, stratified into access-site versus non access-site, were examined according to the TIMI scale in 744 patients with STEMI enrolled in the MULTISTRATEGY trial. TIMI major or minor bleeding complications occurred in 56 (7.5%) patients within 30 days, 46% had an access-site related bleed and 34% required blood transfusion. Bleeding severity and the need for transfusion were equally distributed between site access- versus non-site access related bleeds. After adjustment, patients with any TIMI rated bleed were more likely to die or develop recurrent MI within 12 months (HR 2.1 [95% CI: 1.13 3.8]; p=0.02). This ratio was entirely driven by non-site access-related bleeds (adjusted HR: 2.66 [95% CI: 1.21-5.8]; p=0.007), whereas site-access bleeds were not associated with worse outcomes (HR: 0.74 [95% CI: 0.16-3.4]; p=0.70). CONCLUSIONS: While bleeds of any TIMI severity within 30 days were independently associated with worse cardiovascular outcomes at 12 months, thus confirming previous analyses, this relationship was entirely driven in our study by non access-site related haemorrhagic events. Investigation on whether the site of bleeding complications may preferentially impact cardiovascular outcomes is warranted. PMID- 22311868 TI - Percutaneous effective closure of severe aortic prosthetic paravalvular leak using Amplatzer duct occluder device with the guidance of 3D TEE. PMID- 22311869 TI - Acute myocardial infarction associated with Captagon use. PMID- 22311870 TI - A case of iatrogenic hypothyroidism presented with cardio-inhibitory syncope and resolved by thyroxine supplementation. PMID- 22311871 TI - [Interventional therapy in resistant hypertension; new renal denervation applications in Turkey]. PMID- 22311872 TI - [Analysis of pharmaco-economic assessments on anti-hypertension and anti lipidemia medicines for Turkey]. PMID- 22311873 TI - Arrhythmogenic right ventricular dysplasia and rheumatoid arthritis. PMID- 22311874 TI - A case of Kounis syndrome aggravated by administration of morphine. PMID- 22311875 TI - Echocardiographic assessment in children with Gaucher disease receiving enzyme replacement therapy. PMID- 22311876 TI - Multiple coronary artery-pulmonary artery fistulas in patients with chronic thromboembolic pulmonary hypertension. PMID- 22311877 TI - Broken guidewire during primary percutaneous coronary intervention. PMID- 22311878 TI - Giant cardiac structure in thoracic cavity. PMID- 22311879 TI - Giant right atrial thrombi associated with permanent hemodialysis catheter in a young patient: 3-dimensional echocardiography views. PMID- 22311880 TI - Papillary fibroelastoma of the mitral valve chordae causing transient ischemic attacks. PMID- 22311881 TI - [My editorial's effectiveness]. PMID- 22311882 TI - Stages of change and decisional balance for condom use with a romantic partner. AB - This article examines the relationship between decisional balance and stages of change for consistent condom use with a current romantic heterosexual partner. The sample consisted of 619 undergraduate students (35.1% males; mean of age = 20.31). The results show that the pros and cons of using condoms were significantly related to the stages of change for condom use, but that the pros were more strongly related. Therefore, campaigns for preventing the transmission of the HIV virus and other sexually transmitted diseases should attempt to maximize the perceived advantages of condom use, rather than refuting the cons. PMID- 22311883 TI - Usability evaluation of a web-based support system for people with a schizophrenia diagnosis. AB - BACKGROUND: Routine Outcome Monitoring (ROM) is a systematic way of assessing service users' health conditions for the purpose of better aiding their care. ROM consists of various measures used to assess a service user's physical, psychological, and social condition. While ROM is becoming increasingly important in the mental health care sector, one of its weaknesses is that ROM is not always sufficiently service user-oriented. First, clinicians tend to concentrate on those ROM results that provide information about clinical symptoms and functioning, whereas it has been suggested that a service user-oriented approach needs to focus on personal recovery. Second, service users have limited access to ROM results and they are often not equipped to interpret them. These problems need to be addressed, as access to resources and the opportunity to share decision making has been indicated as a prerequisite for service users to become a more equal partner in communication with their clinicians. Furthermore, shared decision making has been shown to improve the therapeutic alliance and to lead to better care. OBJECTIVE: Our aim is to build a web-based support system which makes ROM results more accessible to service users and to provide them with more concrete and personalized information about their functioning (ie, symptoms, housing, social contacts) that they can use to discuss treatment options with their clinician. In this study, we will report on the usability of the web-based support system for service users with schizophrenia. METHODS: First, we developed a prototype of a web-based support system in a multidisciplinary project team, including end-users. We then conducted a usability study of the support system consisting of (1) a heuristic evaluation, (2) a qualitative evaluation and (3) a quantitative evaluation. RESULTS: Fifteen service users with a schizophrenia diagnosis and four information and communication technology (ICT) experts participated in the study. The results show that people with a schizophrenia diagnosis were able to use the support system easily. Furthermore, the content of the advice generated by the support system was considered meaningful and supportive. CONCLUSIONS: This study shows that the support system prototype has valuable potential to improve the ROM practice and it is worthwhile to further develop it into a more mature system. Furthermore, the results add to prior research into web applications for people with psychotic disorders, in that it shows that this group of end users can work with web-based and computer-based systems, despite the cognitive problems they experience. PMID- 22311884 TI - Cardioprotective effects of insulin: how intensive insulin therapy may benefit cardiac surgery patients. PMID- 22311885 TI - Role of built environments in physical activity, obesity, and cardiovascular disease. PMID- 22311886 TI - Three-dimensional architecture of cardiomyocytes and connective tissues in hypertrophic cardiomyopathy: a scanning electron microscopic observation. PMID- 22311887 TI - Cardiac paraganglioma in an adolescent. PMID- 22311889 TI - Letter by Marques and Morris regarding article, "Signature microRNA expression profile of essential hypertension and its novel link to human cytomegalovirus infection". PMID- 22311890 TI - Letter by De Rango et al regarding article, "Predictors of abdominal aortic aneurysm sac enlargement after endovascular repair". PMID- 22311891 TI - Letter by Fillinger regarding article, "Predictors of abdominal aortic aneurysm sac enlargement after endovascular repair". PMID- 22311892 TI - Increased incidence of thoracic wall deformities in related Bengal kittens. AB - Clinical records made during routine vaccinations were compared between populations of domestic shorthair cats and Bengal kittens. An increased incidence (12/244) of thoracic wall deformity was detected amongst the Bengal kittens. Deformities detected were: pectus excavatum (five), unilateral thoracic wall concavity (six) and scoliosis (one). Five-generation pedigrees were analysed for the affected kittens that showed a high degree of common ancestry indicating the likelihood of a familial cause. PMID- 22311893 TI - The concept of milk kinship in Islam: issues raised when offering preterm infants of Muslim families donor human milk. AB - Research has documented health benefits associated with donor human milk (DHM). Offering DHM to people of the Muslim faith raises important religious concerns for these families. Knowledge of these beliefs and an understanding of the rationale for these beliefs enable the health care team to establish rapport and build a foundation of trust with patients and their families, thereby paving the way to developing a treatment plan that is in the best interest of the patients without compromising care. This article describes the issues and a rationale for them and provides physicians caring for preterm infants of Muslim families with information to facilitate advocating DHM to those families. PMID- 22311894 TI - Losing sight under pressure. AB - A non-communicative patient with vascular dementia who was admitted to hospital with non-specific symptoms. Ophthalmic emergencies are rare, however they should be considered as part of a systemic work-up in unexplained non-specific presentations, particularly in patients who are not able to communicate as in the case we present here. PMID- 22311895 TI - Oropharyngeal dysphagia as a risk factor for malnutrition and lower respiratory tract infection in independently living older persons: a population-based prospective study. AB - OBJECTIVE: to assess the role of oropharyngeal dysphagia (OD) as a risk factor for malnutrition and/or lower respiratory tract infection (LRTI) in the independently-living population of 70 years and over. DESIGN: a population-based cohort study. SUBJECTS AND SETTING: persons 70 years and over in the community (non-institutionalised) were randomly selected from primary care databases. MEASUREMENTS: the volume-viscosity swallow test (V-VST) was administered by trained physicians at baseline to identify subjects with clinical signs of OD and impaired safety or efficacy of swallow. At the one year follow-up visit, hand grip, functional capacity (Barthel score), nutritional status (mini nutritional assessment, MNA) and LRTI (clinical notes) were assessed. RESULTS: two hundred and fifty-four subjects were recruited (46.5% female; mean age, 78 years) and 90% of them (227) were re-evaluated one year later. Annual incidence of 'malnutrition or at risk of malnutrition' (MNA <23.5) was 18.6% in those with basal signs of OD and 12.3% in those without basal signs of OD (P = 0.296). However, prevalent cases of 'malnutrition or at risk of malnutrition' at follow up were associated with basal OD (OR = 2.72; P = 0.010), as well as with basal signs of impaired efficacy of swallow (OR = 2.73; P = 0.015). Otherwise, LRTI's annual incidence was higher in subjects with basal signs of impaired safety of swallow in comparison with subjects without such signs (40.0 versus 21.8%; P = 0.030; OR = 2.39). CONCLUSIONS: OD is a risk factor for malnutrition and LRTI in independently living older subjects. These results suggest that older persons should be routinely screened and treated for OD to avoid nutritional and respiratory complications. PMID- 22311896 TI - Repeat percutaneous coronary revascularization: indications and outcomes in a "real world" cohort. AB - OBJECTIVES: To investigate rates of and reasons for second and subsequent stent procedures in an unselected, "real-world" population. BACKGROUND: Repeat stenting is the primary difference reported in clinical trials of alternative revascularization strategies. The incidence, indication, and outcome for repeat stenting in contemporary practice outside the more selective populations of trials and registries has not been described. METHOD: All patients undergoing a first percutaneous coronary intervention (PCI) procedure with stenting from January 2001 to August 2009 (10,509) from a large UK tertiary referral and district general hospital were identified. Mortality and the incidence, timing, and indication for repeat revascularization in this population were investigated from patient records. RESULTS: Of 10,509 patients undergoing a first PCI and stent implant 23.5% underwent repeat angiography of which 11.2% required repeat PCI and 2% coronary artery bypass grafting (median follow-up of 3.8 years). A total of 1.3% went on to a third PCI. The commonest indication for repeat stenting was disease progression remote from the original stent (46%) and planned staged PCI (23%); 21% had a stent-related indication. Functional assessment before repeat stenting was used in one-third of stable patients. Mortality was 2.5% per annum. CONCLUSIONS: In contemporary practice, patients undergoing a first stenting procedure have a low subsequent mortality, and the substantial majority (86.4%) requires no further revascularization over a median 3.8 year follow-up. For those who do require repeat stenting, this is most commonly at a site remote from the first stent. PMID- 22311897 TI - Tissue-specific upregulation of angiotensin-converting enzyme 1 in spontaneously hypertensive rats through histone code modifications. AB - The renin-angiotensin system has been implicated in the development of hypertension and damages several organs. The expressions of the components of a local renin-angiotensin system (RAS) in the hypertensive rats differ from those of the normotensive rats. We hypothesized that local tissue-specific upregulation of angiotensin-converting enzyme 1 (ACE1) in hypertension is caused by epigenetic changes. Adrenal gland, aorta, heart, kidney, liver, and lung tissues were excised from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Ace1 mRNA and protein expressions were measured by real-time PCR and Western blot, respectively. Promoter methylation was revealed by bisulfite sequencing. Histone modifications, such as histone 3 acetylation (H3Ac), fourth lysine trimethylation (H3K4me3), and ninth lysine dimethylation (H3K9me2), were quantified by chromatin immunoprecipitation (ChIP), followed by real-time PCR. The expressions and associations of chromatin remodeling genes were analyzed by real-time PCR and ChIP, respectively. Local tissues from SHRs showed higher expressions of Ace1 mRNA and protein than those from the WKY rats. Ace1 promoter was mostly unmethylated in all of the tissues from both strains. The Ace1 promoter regions of SHR tissues were more enriched with H3Ac and H3K4me3, except in the lungs. The adrenal glands, hearts, and kidneys of SHRs showed less enrichment with H3K9me2. Valsartan treatment in SHRs decreased local Ace1 mRNA and protein expressions, which were accompanied by higher H3K9me2, as well as less H3Ac and H3K4me3. In conclusion, ACE1 is upregulated in local tissues of SHRs via histone code modifications. PMID- 22311898 TI - Ambulatory versus home versus clinic blood pressure. PMID- 22311899 TI - The role of angiogenic factors in the prediction and diagnosis of preeclampsia superimposed on chronic hypertension. PMID- 22311900 TI - Sympathetic signatures of cardiovascular disease: a blueprint for development of targeted sympathetic ablation therapies. PMID- 22311901 TI - Is low diastolic blood pressure an independent risk for cardiovascular events in patients with manifest atherosclerotic disease? PMID- 22311902 TI - Central angiotensin type 1 receptor blockade decreases cardiac but not renal sympathetic nerve activity in heart failure. AB - In heart failure (HF), cardiac sympathetic nerve activity (SNA; CSNA) is increased, which has detrimental effects on the heart and promotes arrhythmias and sudden death. There is evidence that the central renin-angiotensin system plays an important role in stimulating renal SNA in HF. Because SNA to individual organs is differentially controlled, we have investigated whether central angiotensin receptor blockade decreases CSNA in HF. We simultaneously recorded CSNA and renal SNA in conscious normal sheep and in sheep with HF induced by rapid ventricular pacing (ejection fraction: <40%). The effect of blockade of central angiotensin type 1 receptors by intracerebroventricular infusion of losartan (1 mg/h for 5 hours) on resting levels and baroreflex control of CSNA and renal SNA were determined. In addition, the levels of angiotensin receptors in central autonomic nuclei were determined using autoradiography. Sheep in HF had a large increase in CSNA (43+/-2 to 88+/-3 bursts per 100 heart beats; P<0.05) and heart rate, with no effect on renal SNA. In HF, central infusion of losartan for 5 hours significantly reduced the baseline levels of CSNA (to 69+/-5 bursts per 100 heart beats) and heart rate. Losartan had no effect in normal animals. In HF, angiotensin receptor levels were increased in the paraventricular nucleus and supraoptic nucleus but reduced in the area postrema and nucleus tractus solitarius. In summary, infusion of losartan reduced the elevated levels of CNSA in an ovine model of HF, indicating that central angiotensin receptors play a critical role in stimulating the increased sympathetic activity to the heart. PMID- 22311903 TI - Synergistic effect of norepinephrine transporter blockade and alpha-2 antagonism on blood pressure in autonomic failure. AB - Patients with autonomic failure have disabling orthostatic hypotension because of impaired sympathetic activity. Norepinephrine transporter blockade with atomoxetine raises blood pressure in autonomic failure by increasing synaptic norepinephrine concentrations in postganglionic sympathetic neurons. This effect requires tonic release of norepinephrine, which is decreased in patients with low sympathetic tone. We hypothesized that increasing residual sympathetic outflow with the alpha-2 antagonist yohimbine would potentiate the pressor effect of norepinephrine transporter blockade with atomoxetine and improve orthostatic tolerance in peripheral autonomic failure. Seventeen patients received a single oral dose of either placebo, yohimbine 5.4 mg or atomoxetine 18.0 mg, and the combination yohimbine and atomoxetine in a single blind, crossover study. Blood pressure was assessed while patients were seated and standing for <=10 minutes before and 1 hour postdrug. Neither yohimbine nor atomoxetine significantly increased seated systolic blood pressure or orthostatic tolerance compared with placebo. The combination, however, significantly increased seated systolic blood pressure and orthostatic tolerance (P<0.001 and P=0.016, respectively) in a synergistic manner. The maximal increase in seated systolic blood pressure seen with the combination was 31+/-33 mm Hg at 60 minutes postdrug. Only the combination showed a significant improvement in orthostatic symptoms. In conclusion, the combination of yohimbine and atomoxetine had a synergistic effect on blood pressure and orthostatic tolerance in peripheral autonomic failure, which may be explained by an increased release of norepinephrine in peripheral sympathetic neurons by alpha-2 antagonism combined with a reduced norepinephrine clearance by norepinephrine transporter blockade. Safety studies are required to address the clinical usefulness of this pharmacological approach. PMID- 22311904 TI - New therapies for postural hypotension. PMID- 22311905 TI - Suboptimal inhibition of platelet cyclooxygenase-1 by aspirin in metabolic syndrome. AB - Interindividual variation in the ability of aspirin to inhibit platelet cyclooxygenase-1 (COX-1) could account for some on-treatment cardiovascular events. Here, we sought to determine whether there are clinical phenotypes that are associated with a suboptimal pharmacological effect of aspirin. In a prospective, 2-week study, we evaluated the effect of aspirin (81 mg) on platelet COX-1 in 135 patients with stable coronary artery disease by measuring serum thromboxane B(2) (sTxB(2)) as an indicator of inhibition of platelet COX-1. A nested randomized study compared enteric-coated with immediate-release formulations of aspirin. We found that sTxB(2) was systematically higher among the 83 patients with metabolic syndrome than among the 52 patients without (median: 4.0 versus 3.02 ng/mL; P=0.013). Twelve patients (14%) with metabolic syndrome, but none without metabolic syndrome, had sTxB(2) levels consistent with inadequate inhibition of COX (sTxB(2) >=13 ng/mL). In linear regression models, metabolic syndrome (but none of its individual components) significantly associated with higher levels of log-transformed sTxB(2) (P=0.006). Higher levels of sTxB(2) associated with greater residual platelet function measured by aggregometry-based methods. Among the randomized subset, sTxB(2) levels were systematically higher among patients receiving enteric-coated aspirin. Last, urinary 11-dehydro thromboxane B(2) did not correlate with sTxB(2), suggesting that the former should not be used to quantitate aspirin's pharmacological effect on platelets. In conclusion, metabolic syndrome, which places patients at high risk for thrombotic cardiovascular events, strongly and uniquely associates with less effective inhibition of platelet COX-1 by aspirin. PMID- 22311906 TI - Aldosterone blunts tubuloglomerular feedback by activating macula densa mineralocorticoid receptors. AB - Chronic aldosterone administration increases glomerular filtration rate, whereas inhibition of mineralocorticoid receptors (MRs) markedly attenuates glomerular hyperfiltration and hypertension associated with primary aldosteronism or obesity. However, the mechanisms by which aldosterone alters glomerular filtration rate regulation are poorly understood. In the present study, we hypothesized that aldosterone suppresses tubuloglomerular feedback (TGF) via activation of macula densa MR. First, we observed the expression of MR in macula densa cells isolated by laser capture microdissection and by immunofluorescence in rat kidneys. Second, to investigate the effects of aldosterone on TGF in vitro, we microdissected the juxtaglomerular apparatus from rabbit kidneys and perfused the afferent arteriole and distal tubule simultaneously. Under control conditions, TGF was 2.8+/-0.2 MUm. In the presence of aldosterone (10(-8) mol/L), TGF was reduced by 50%. The effect of aldosterone to attenuate TGF was blocked by the MR antagonist eplerenone (10(-5) mol/L). Third, to investigate the effect of aldosterone on TGF in vivo, we performed micropuncture, and TGF was determined by maximal changes in stop-flow pressure P(sf) when tubular perfusion rate was increased from 0 to 40 nL/min. Aldosterone (10(-7) mol/L) decreased DeltaP(sf) from 10.1+/-1.4 to 7.7+/-1.2 mm Hg. In the presence of l-NG-monomethyl arginine citrate (10(-3) mol/L), this effect was blocked. We conclude that MRs are expressed in macula densa cells and can be activated by aldosterone, which increases nitric oxide production in the macula densa and blunts the TGF response. PMID- 22311907 TI - Angiogenic factors in superimposed preeclampsia: a longitudinal study of women with chronic hypertension during pregnancy. AB - Imbalances in circulating angiogenic factors contribute to the pathogenesis of preeclampsia. To characterize levels of angiogenic factors in pregnant women with chronic hypertension, we prospectively followed 109 women and measured soluble fms-like tyrosine kinase 1 (sFlt1), soluble endoglin, and placental growth factor at 12, 20, 28, and 36 weeks' gestation and postpartum. Superimposed preeclampsia developed in 37 (34%) and was early onset (<34 weeks) in 9 and later onset (>=34 weeks) in 28. Circulating levels of sFlt1 and the ratio of sFlt1 to placental growth factor were higher before clinical diagnosis at 20 weeks' gestation in women who subsequently developed early onset preeclampsia between 28 and 34 weeks compared with levels in women who never developed preeclampsia (P=0.001) or who developed late-onset preeclampsia (P=0.001). Circulating levels of sFlt1, soluble endoglin, and the ratio of sFlt1:placental growth factor were also significantly higher, and placental growth factor levels were significantly lower at the time of clinical diagnosis of superimposed preeclampsia in women with either early or late-onset superimposed preeclampsia compared with levels at similar gestational ages in those with uncomplicated chronic hypertension. We conclude that alterations in angiogenic factors are detectable before and at the time of clinical diagnosis of early onset superimposed preeclampsia, whereas alterations were observed only at the time of diagnosis in women with late-onset superimposed preeclampsia. Longitudinal measurements of angiogenic factors may help anticipate early onset superimposed preeclampsia and facilitate diagnosis of superimposed preeclampsia in women with chronic hypertension. PMID- 22311908 TI - Ouabain and insulin induce sodium pump endocytosis in renal epithelium. AB - Cardiotonic steroids signaling through the basolateral sodium pump (Na/K-ATPase) have been shown to alter renal salt handling in intact animals. Because the relationship between renal salt handling and blood pressure is a key determinant of hypertension, and patients with insulin resistance are frequently hypertensive, we chose to examine whether there might be competition for resources necessary for receptor-mediated endocytosis. In LLC-PK1 cells, the Na/K ATPase-alpha1 and carcinoembryonic antigen cell adhesion molecule 1, a plasma membrane protein that promotes receptor-mediated endocytosis, colocalized in the plasma membranes and translocated to the intracellular region in response to ouabain. Either ouabain or insulin alone caused accumulation of and carcinoembryonic antigen cell adhesion molecule, as well as insulin receptor beta, and epidermal growth factor receptor in early endosomes, but no synergy was demonstrable. Like ouabain, insulin also caused c-Src activation. When caveolin or Na/K-ATPase-alpha1 expression was knocked down with small interfering RNA, insulin but not ouabain induced carcinoembryonic antigen cell adhesion molecule 1, insulin receptor-beta, and epidermal growth factor receptor endocytosis. To determine whether this might be relevant to salt handling in vivo, we examined salt loading in mice with null renal carcinoembryonic antigen cell adhesion molecule 2 expression. The null renal carcinoembryonic antigen cell adhesion molecule 2 animals demonstrated greater increases in blood pressure with increases in dietary salt than control animals. These data demonstrate that cardiotonic steroids and insulin compete for cellular endocytosis resources and suggest that, under conditions where circulating insulin concentrations are high, cardiotonic steroid-mediated natriuresis could be impaired. PMID- 22311909 TI - Mice lacking hypertension candidate gene ATP2B1 in vascular smooth muscle cells show significant blood pressure elevation. AB - We reported previously that ATP2B1 was one of the genes for hypertension receptivity in a large-scale Japanese population, which has been replicated recently in Europeans and Koreans. ATP2B1 encodes the plasma membrane calcium ATPase isoform 1, which plays a critical role in intracellular calcium homeostasis. In addition, it is suggested that ATP2B1 plays a major role in vascular smooth muscle contraction. Because the ATP2B1 knockout (KO) mouse is embryo-lethal, we generated mice with vascular smooth muscle cell-specific KO of ATP2B1 using the Cre-loxP system to clarify the relationship between ATP2B1 and hypertension. The KO mice expressed significantly lower levels of ATP2B1 mRNA and protein in the aorta compared with control mice. KO mice showed significantly higher systolic blood pressure as measured by tail-cuff method and radiotelemetric method. Similar to ATP2B1, the expression of the Na(+)-Ca(2+) exchanger isoform 1 mRNA was decreased in vascular smooth muscle cells of KO mice. However, ATP2B4 expression was increased in KO mice. The cultured vascular smooth muscle cells of KO mice showed increased intracellular calcium concentration not only in basal condition but also in phenylephrine-stimulated condition. Furthermore, phenylephrine-induced vasoconstriction was significantly increased in vascular rings of the femoral artery of KO mice. These results suggest that ATP2B1 plays important roles in the regulation of blood pressure through alteration of calcium handling and vasoconstriction in vascular smooth muscle cells. PMID- 22311910 TI - Gender-specific differences in myocardial deformation and aortic stiffness at rest and dobutamine stress. AB - Elderly women have increased aortic and ventricular stiffness but preserved global systolic function. Possible gender differences in ventricular deformation attributed to increased aortic stiffness at rest or with positive inotropic stress remain unknown. Eighty-four subjects (mean age: 63+/-8 years) were assessed for aortic stiffness by pulse wave velocity and ventricular deformation at rest and during dobutamine stress using magnetic resonance. At rest, women (n=40) had greater aortic stiffness and ventricular deformation than men (P<0.05). In men, dobutamine increased longitudinal (mean+/-SD: 3.3+/-4.1%; P<0.01) and circumferential deformation (2.9+/-5.1%; P=0.007), whereas women showed an increase in circumferential deformation only (4.8+/-6.3%; P<0.01). In men there was an inverse association between longitudinal deformation and pulse wave velocity at rest (r=-0.51; P=0.002) and linear at stress (r=0.52; P=0.001). In women there were no significant relations at rest, whereas at stress longitudinal deformation was inversely associated with pulse wave velocity (r= 0.43; P=0.02). We demonstrate gender-specific differences in the relationship between aortic stiffness and ventricular deformation at rest and during dobutamine stress. Although at rest longitudinal deformation is inversely related to aortic stiffness in men, there is no such relationship in women. At stress, men improve longitudinal function, whereas in women such response is limited. PMID- 22311911 TI - Ambrisentan and tadalafil synergistically relax endothelin-induced contraction of rat pulmonary arteries. AB - Endothelin receptor antagonists and phosphodiesterase type 5 inhibitors are used to treat pulmonary arterial hypertension. We tested the hypothesis that a selective endothelin type A receptor antagonist (ambrisentan) and a phosphodiesterase type 5 inhibitor (tadalafil) may act synergistically to relax endothelin-constricted pulmonary arteries. Rat isolated intrapulmonary arterial rings contracted with 8 nmol/L endothelin-1 were relaxed by 10 nmol/L ambrisentan and 30 nmol/L tadalafil alone by 26+/-3% and 21+/-1%, respectively, whereas both drugs in combination acted synergistically to relax arterial rings by 83+/-6%. The nonselective endothelin type A and B receptor antagonists bosentan (100 nmol/L) and macitentan (30 nmol/L) alone relaxed endothelin-contracted rings by 30+/-5% and 24+/-3%, respectively. Combinations of 30 nmol/L tadalafil with 100 nmol/L bosentan or 30 nmol/L macitentan relaxed endothelin-contracted rings by 53+/-5% or 46+/-7%, respectively; these values are similar to the calculated sums of the individual effects of these compounds. Denudation of endothelium from pulmonary arterial rings abolished the vasodilator response to 30 nmol/L tadalafil and the synergistic vasorelaxant effect of tadalafil with ambrisentan. In the presence of 1 MUmol/L BQ-788, a selective endothelin type B receptor antagonist, the vasorelaxant effects of 10 nmol/L ambrisentan and 30 nmol/L tadalafil were additive but not synergistic. These data can be interpreted to suggest that ambrisentan and tadalafil synergistically inhibit endothelin-1 induced constriction of rat intrapulmonary arteries and that endothelin type B receptors in endothelium are necessary to enable a synergistic vasorelaxant effect of the drug combination. PMID- 22311912 TI - Treatment of scaphoid nonunion using an autologous bone screw. PMID- 22311913 TI - Suboptimal positioning of fragment-specific palmar distal radius plates. PMID- 22311914 TI - Acute carpal tunnel syndrome complicating a distal radial fracture in a patient with a persistent median artery. PMID- 22311915 TI - Posterior interosseous nerve palsy after needle acupuncture. PMID- 22311916 TI - Anatomical collateral ligament reconstruction in the hand using intraosseous suture anchors and a free tendon graft. AB - We describe anatomical collateral ligament reconstruction using a free tendon graft and intraosseous suture anchors in the digits. Eleven patients who underwent collateral ligament reconstruction at the proximal interphalangeal or metacarpophalangeal joints were enrolled in this study. Proper and accessory collateral ligaments were reconstructed using a free tendon graft in an anatomical configuration and the grafted tendons were fixed with suture anchors. The mean time from surgery to last follow-up was 9.2 months. All anchors used for fixation of grafted tendons remained securely at their original positions at the last follow-up visits. No significant complications were associated with the use of anchors. Clinical results were excellent in 10 patients and good in one. Anatomical reconstruction of collateral ligaments using suture anchors is simpler, faster, and safer than the conventional bone tunnel technique and it does not have the risks of breakage of bone bridges, skin irritation, or graft loosening. PMID- 22311917 TI - Medium-term outcomes of pyrocarbon arthroplasty of the proximal interphalangeal joint. AB - We evaluated the outcome of pyrocarbon arthroplasty for proximal interphalangeal joint osteoarthritis in 18 arthroplasties carried out by a single surgeon using the Ascension prosthesis (Ascension Orthopedics Inc., Austin, Texas) in 15 patients after a mean of 6.2 years. Significant and maintained improvements in pain scores at rest and on active movements were achieved for surviving implants, and the range of motion was comparable with preoperative measurements. The radiographs, which were evaluated for evidence of ongoing migration and potential failure, were of concern in 10 out of 18 joints. Two patients required implant removal. PMID- 22311918 TI - A pilot study assessing the effectiveness of postoperative splinting after limited fasciectomy for Dupuytren's disease. AB - Before surgery for Dupuytren's contracture, 54 patients with a proximal interphalangeal (PIP) joint flexion contractures of at least 30 degrees were randomized to receive either a 3-month splinting protocol together with hand therapy under the direct supervision of hand therapists, or the same hand therapy alone. Extension deficit of the PIP joint (primary outcome measure), global perceived effect, pain intensity, comfort and complications were assessed at baseline and 1 year after surgery. In an intention-to-treat analysis, the group assigned to splint-plus-hand therapy had a mean reduction of 21 degrees in flexion contracture after 1 year, compared with 29 degrees in the group receiving hand therapy alone (p = 0.1). There was no difference between the groups regarding other parameters. After operative release of a Dupuytren's contracture, a postoperative protocol using a splint and hand therapy was no better than hand therapy alone in minimizing postoperative flexion contractures. PMID- 22311919 TI - Tendon transfer for radial nerve palsy: a single tendon to restore finger extension as well as thumb extension/radial abduction. AB - Since 1994, the author has been treating irreparable radial nerve palsy with pronator teres to the extensor carpi radialis brevis (for wrist extension) and a single tendon (flexor carpi radialis or ulnaris) transfer to restore finger extension as well as thumb extension/radial abduction. We sought to investigate whether these patients are able to flex the fingers with the thumb in abduction/extension posture. This was a prospective study over a 5-year period, and the results of this transfer in 15 consecutive patients (mean age 28 years) were analyzed. At final follow-up (mean 30 months), all patients had reasonable wrist movement, finger extension, and thumb extension/radial abduction. The overall results were rated excellent in 12 patients and good in the remaining three patients according to the Bincaz scale. More interesting was the ability of all patients to flex their fingers with only mild relaxation of the extended/abducted thumb. PMID- 22311920 TI - Established and emerging markers of kidney function. AB - BACKGROUND: The kidney performs a multitude of essential functions to maintain homeostasis. In clinical medicine, glomerular filtration rate (GFR) provides the best index of overall kidney function, and proteinuria adds additional information on renal and nonrenal prognosis. Several novel biomarkers of kidney injury and function are under investigation. CONTENT: Plasma creatinine concentration is the most widely used measure for estimation of GFR. Plasma cystatin C and beta-trace protein may eventually prove to be superior to creatinine. GFR may be measured directly by use of exogenous filtration markers, although their role is primarily limited to the research setting. Real-time, noninvasive measurement of GFR by using fluorescently labeled markers may be available in the future. Novel biomarkers of tubular injury such as neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, liver-type fatty acid binding protein, N-acetyl-beta-(D)-glucosaminidase, and interleukin-18 may enable the early detection of acute kidney injury before or in the absence of a change in GFR. SUMMARY: A variety of methods are available to assist clinicians in the assessment of kidney function and injury. Ongoing investigation will help determine the utility of several new markers and clarify their role in the care of patients with and at risk for kidney disease. PMID- 22311921 TI - The obesity epidemic. PMID- 22311922 TI - Streptococcus pneumoniae can utilize multiple sources of hyaluronic acid for growth. AB - The mechanisms by which Streptococcus pneumoniae obtains carbohydrates for growth during airway colonization remain to be elucidated. The low concentration of free carbohydrates in the normal human airway suggests that pneumococci must utilize complex glycan structures for growth. The glycosaminoglycan hyaluronic acid is present on the apical surface of airway epithelial cells. As pneumococci express a hyaluronate lyase (Hyl) that cleaves hyaluronic acid into disaccharides, we hypothesized that during colonization pneumococci utilize the released carbohydrates for growth. Hyaluronic acid supported significant pneumococcal growth in an hyl-dependent manner. A phosphoenolpyruvate-dependent phosphotransferase system (PTS) and an unsaturated glucuronyl hydrolase (Ugl) encoded downstream of hyl are also essential for growth on hyaluronic acid. This genomic arrangement is present in several other organisms, suggesting conservation of the utilization mechanism between species. In vivo experiments support the hypothesis that S. pneumoniae utilizes hyaluronic acid as a carbon source during colonization. We also demonstrate that pneumococci can utilize the hyaluronic acid capsule of other bacterial species for growth, suggesting an alternative carbohydrate source for pneumococcal growth. Together, these data support a novel function for pneumococcal degradation of hyaluronic acid in vivo and provide mechanistic details of growth on this glycosaminoglycan. PMID- 22311923 TI - Bundle-forming pilus locus of Aeromonas veronii bv. Sobria. AB - Little is known about the colonization mechanisms of Aeromonas spp. Previous work has suggested that the type IV bundle-forming pilus (Bfp) is an aeromonad intestinal colonization factor. This study provides the first genetic characterization of this structure. To define the role of Bfp in Aeromonas veronii bv. Sobria adherence, a 22-kb locus encoding the bundle-forming pilus was isolated; this contained 17 pilus-related genes similar to the mannose-sensitive hemagglutinin (MSHA) of Vibrio cholerae. Reverse transcriptase PCR (RT-PCR) demonstrated that the locus had two major transcriptional units, mshI to mshF and mshB to mshQ. Transcriptional fusion experiments demonstrated the presence of two strong promoters upstream of mshI and mshB. The locus encoded four putative prepilin proteins, one of which (MshA) corresponded to the N-terminal sequence of the previously isolated major pilin protein. All the pilin genes were inactivated, mutation of each minor or major pilin gene greatly reduced the bacterium's ability to adhere and form biofilms, and complementation of each mutant in trans rescued this phenotype. Mutation of the major pilin MshA and MshB, a minor pilin, resulted in their loss. The position of the mshH gene is conserved within a number of bacteria, and we have shown it is not transcriptionally linked to the other msh genes; moreover, its mutation did not have a dramatic effect on either adhesion or biofilm formation. We conclude that the bundle-forming pilus is required for A. veronii bv. Sobria adherence and biofilm formation; furthermore, both the major and minor pilin proteins are essential for this process. PMID- 22311924 TI - Expression, immunogenicity, histopathology, and potency of a mosquito-based malaria transmission-blocking recombinant vaccine. AB - Vaccines have been at the forefront of global research efforts to combat malaria, yet despite several vaccine candidates, this goal has yet to be realized. A potentially effective approach to disrupting the spread of malaria is the use of transmission-blocking vaccines (TBV), which prevent the development of malarial parasites within their mosquito vector, thereby abrogating the cascade of secondary infections in humans. Since malaria is transmitted to human hosts by the bite of an obligate insect vector, mosquito species in the genus Anopheles, targeting mosquito midgut antigens that serve as ligands for Plasmodium parasites represents a promising approach to breaking the transmission cycle. The midgut specific anopheline alanyl aminopeptidase N (AnAPN1) is highly conserved across Anopheles vectors and is a putative ligand for Plasmodium ookinete invasion. We have developed a scalable, high-yield Escherichia coli expression and purification platform for the recombinant AnAPN1 TBV antigen and report on its marked vaccine potency and immunogenicity, its capacity for eliciting transmission-blocking antibodies, and its apparent lack of immunization associated histopathologies in a small-animal model. PMID- 22311925 TI - Campylobacter jejuni disrupts protective Toll-like receptor 9 signaling in colonic epithelial cells and increases the severity of dextran sulfate sodium induced colitis in mice. AB - Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation associated with a dysregulated immune response to commensal bacteria in susceptible individuals. The relapse of IBD may occur following an infection with Campylobacter jejuni. Apical epithelial Toll-like receptor 9 (TLR9) activation by bacterial DNA is reported to maintain colonic homeostasis. We investigated whether a prior C. jejuni infection disrupts epithelial TLR9 signaling and increases the severity of disease in a model of mild dextran sulfate sodium (DSS) colitis in mice. In a further attempt to identify mechanisms, T84 monolayers were treated with C. jejuni followed by a TLR9 agonist. Transepithelial resistance (TER) and dextran flux across confluent monolayers were monitored. Immunohistochemistry, Western blotting, and flow cytometry were used to examine TLR9 expression. Mice colonized by C. jejuni lacked any detectable pathology; however, in response to low levels of DSS, mice previously exposed to C. jejuni exhibited significantly reduced weight gain and increased occult blood and histological damage scores. Infected mice treated with DSS also demonstrated a significant reduction in levels of the anti-inflammatory cytokine interleukin-25. In vitro studies indicated that apical application of a TLR9 agonist enhances intestinal epithelial barrier function and that this response is lost in C. jejuni-infected monolayers. Furthermore, infected cells secreted significantly more CXCL8 following the basolateral application of a TLR9 agonist. Surface TLR9 expression was reduced in C. jejuni-infected monolayers subsequently exposed to a TLR9 agonist. In conclusion, infection by C. jejuni disrupts TLR9-induced reinforcement of the intestinal epithelial barrier, and colonization by C. jejuni increases the severity of mild DSS colitis. PMID- 22311926 TI - Strain-specific regulatory role of eukaryote-like serine/threonine phosphatase in pneumococcal adherence. AB - Streptococcus pneumoniae exploits a battery of virulence factors to colonize the host. Although the eukaryote-like Ser/Thr kinase of S. pneumoniae (StkP) has been implicated in physiology and virulence, the role of its cotranscribing phosphatase (PhpP) has remained elusive. The construction of nonpolar markerless phpP knockout mutants (DeltaphpP) in two pathogenic strains, D39 (type 2) and 6A EF3114 (type 6A), indicated that PhpP is not indispensable for pneumococcal survival. Further, PhpP also participates in the regulation of cell wall biosynthesis/division, adherence, and biofilm formation in a strain-specific manner. Additionally, we provide hitherto-unknown in vitro and in vivo evidence of a physiologically relevant biochemical link between the StkP/PhpP-mediated cognate regulation and the two-component regulatory system TCS06 (RR06/HK06) that regulates the expression of the gene encoding an important pneumococcal surface adhesin, CbpA, which was found to be significantly upregulated in DeltaphpP mutants. In particular, StkP (threonine)-phosphorylated RR06 bound to the cbpA promoter with high efficiency even in the absence of the HK06-responsive and catalytically active aspartate 51 residue. Together, our findings unravel the significant contributions of PhpP in pneumococcal physiology and adherence. PMID- 22311927 TI - DksA-dependent resistance of Salmonella enterica serovar Typhimurium against the antimicrobial activity of inducible nitric oxide synthase. AB - In coordination with the ppGpp alarmone, the RNA polymerase regulatory protein DksA controls the stringent response of eubacteria, negatively regulating transcription of translational machinery and directly activating amino acid promoters and de novo amino acid biosynthesis. Given the effects of nitric oxide (NO) on amino acid biosynthetic pathways and the intimate relationship of DksA with amino acid synthesis and transport, we tested whether DksA contributes to the resistance of Salmonella to reactive nitrogen species (RNS). Our studies show that the zinc finger predicted to position DksA in the secondary channel of the RNA polymerase is essential for the resistance of Salmonella enterica serovar Typhimurium to RNS in a murine model of systemic salmonellosis. Despite exhibiting auxotrophies for various amino acids, DeltadksA mutant Salmonella strains regain virulence in mice lacking inducible NO synthase (iNOS). DksA is also important for growth of this intracellular pathogen in the presence of NO congeners generated by iNOS during the innate response of murine macrophages. Accordingly, dksA mutant Salmonella strains are hypersusceptible to chemically generated NO, a phenotype that can be prevented by adding amino acids. The DksA dependent antinitrosative defenses do not rely on the Hmp flavohemoprotein that detoxifies NO to NO(3)(-) and appear to operate independently of the ppGpp alarmone. Our investigations are consistent with a model by which NO produced in the innate response to Salmonella exerts considerable pressure on amino acid biosynthesis. The cytotoxicity of NO against Salmonella amino acid biosynthetic pathways is antagonized in great part by the DksA-dependent regulation of amino acid biosynthesis and transport. PMID- 22311928 TI - Virulence of Escherichia coli clinical isolates in a murine sepsis model in relation to sequence type ST131 status, fluoroquinolone resistance, and virulence genotype. AB - Escherichia coli sequence type ST131 (O25b:H4) has emerged over the past decade as a globally disseminated, multidrug-resistant pathogen. Unlike traditional antimicrobial-resistant E. coli, ST131 derives from virulence-associated phylogenetic group B2 and exhibits extraintestinal virulence factors. This, plus preliminary evidence of virulence in experimental animals, has suggested that ST131's epidemic emergence may be due to high virulence potential, compared with other E. coli types. To test this hypothesis, we compared a large number of matched ST131 and non-ST131 E. coli clinical isolates, both fluoroquinolone resistant and susceptible, plus isolates from classic extraintestinal pathogenic E. coli (ExPEC) sequence types (STs) and case report ST131 household transmission isolates, for virulence in a mouse subcutaneous sepsis model. Overall, in mice, the study isolates produced a wide range of lethality and clinical illness. However, neither ST131 status nor fluoroquinolone phenotype correlated with this diversity of illness severity, which occurred within each of the 6 study groups. In contrast, multiple known or suspected ExPEC virulence genes, including pap (P fimbriae), vat (vacuolating toxin), kpsM II (group 2 capsule), ibeA (invasion of brain endothelium), and clbB/N (colibactin synthesis), plus molecularly defined ExPEC status, were significantly associated with virulence. These findings point away from ST131 isolates as having higher virulence potential compared with other E. coli types in causing invasive extraintestinal infections and suggest instead that ST131's epidemiological success may reflect enhanced fitness for upstream steps in pathogenesis or in colonization and transmission. Additionally, the extensive within-ST virulence diversity suggests an opportunity to compare closely related strains to identify the responsible genetic determinants. PMID- 22311929 TI - Predicting outcome of IV thrombolysis-treated ischemic stroke patients: the DRAGON score. AB - OBJECTIVE: To develop a functional outcome prediction score, based on immediate pretreatment parameters, in ischemic stroke patients receiving IV alteplase. METHODS: The derivation cohort consists of 1,319 ischemic stroke patients treated with IV alteplase at the Helsinki University Central Hospital, Helsinki, Finland. We evaluated the predictive value of parameters associated with the 3-month outcome and developed the score according to the magnitude of logistic regression coefficients. We assessed accuracy of the model with bootstrapping. External validation was performed in a cohort of 330 patients treated at the University Hospital Basel, Basel, Switzerland. We assessed the score performance with area under the receiver operating characteristic curve (AUC-ROC). RESULTS: The DRAGON score (0-10 points) consists of (hyper)Dense cerebral artery sign/early infarct signs on admission CT scan (both = 2, either = 1, none = 0), prestroke modified Rankin Scale (mRS) score >1 (yes = 1), Age (>= 80 years = 2, 65-79 years = 1, <65 years = 0), Glucose level at baseline (>8 mmol/L [>144 mg/dL] = 1), Onset-to treatment time (>90 minutes = 1), and baseline National Institutes of Health Stroke Scale score (>15 = 3, 10-15 = 2, 5-9 = 1, 0-4 = 0). AUC-ROC was 0.84 (0.80 0.87) in the derivation cohort and 0.80 (0.74-0.86) in the validation cohort. Proportions of patients with good outcome (mRS score 0-2) were 96%, 88%, 74%, and 0% for 0-1, 2, 3, and 8-10 points, respectively. Proportions of patients with miserable outcome (mRS score 5-6) were 0%, 2%, 5%, 70%, and 100% for 0-1, 2, 3, 8, and 9-10 points, respectively. External validation showed similar results. CONCLUSIONS: The DRAGON score is valid at our site and was reliable externally. It can support clinical decision-making, especially when invasive add-on strategies are considered. The score was not studied in patients with basilar artery occlusion. Further external validation is warranted. PMID- 22311930 TI - Basilar leptomeningitis in Vogt-Koyanagi-Harada disease. PMID- 22311931 TI - So what? Does the test lead to improved health outcomes? PMID- 22311932 TI - Pearls & Oysters: the effects of renal replacement therapy on cerebral autoregulation. PMID- 22311933 TI - Teaching NeuroImages: armored brain. PMID- 22311934 TI - Teaching Video NeuroImages: spinal and bulbar muscular atrophy mimicking essential tremor. PMID- 22311935 TI - Methicillin-resistant Staphylococcus aureus bacteraemia and endocarditis treated with ceftaroline salvage therapy. AB - BACKGROUND: One of the newest methicillin-resistant Staphylococcus aureus (MRSA) antibiotics to receive FDA approval is ceftaroline fosamil, a member of a new subclass of cephalosporins with unique activity against MRSA. However, ceftaroline is currently only FDA approved for complicated skin/soft tissue infections and community-acquired pneumonia; there are currently no clinical data regarding its use in MRSA bacteraemia and endocarditis. We report a series of six patients in which ceftaroline was utilized as salvage monotherapy in persistent MRSA bacteraemia or endocarditis. METHODS: Using pharmacy records, 11 ceftaroline treated patients were identified between January 2011 and November 2011 at University Health System and the South Texas Veterans Health Care System in San Antonio, TX, USA. All cases were reviewed and six patients received ceftaroline therapy for MRSA bacteraemia or endocarditis due to persistent or recurrent bacteraemia while on standard antibiotics (vancomycin or daptomycin). RESULTS: All six patients experienced rapid clearance of their bacteraemia after starting ceftaroline. In the case of endocarditis for which the patient subsequently developed heart failure and required valve replacement, there was no evidence of growth from cultures taken from the excised valve, suggesting sterilization within 13 days of starting ceftaroline. CONCLUSIONS: Ceftaroline exhibits potent anti-MRSA activity in both in vitro and animal studies, including rabbit endocarditis models; however, the lack of clinical data has limited its use in bacteraemia and endovascular infections in humans. We hope that this series serves as an initial stepping stone for further evaluation of this compound for more invasive infections due to MRSA. PMID- 22311936 TI - Novel inhibitory activity of the Staphylococcus aureus NorA efflux pump by a kaempferol rhamnoside isolated from Persea lingue Nees. AB - OBJECTIVES: To isolate a plant-derived compound with efflux inhibitory activity towards the NorA transporter of Staphylococcus aureus. METHODS: Bioassay-guided isolation was used, with inhibition of ethidium bromide efflux via NorA as a guide. Characterization of activity was carried out using MIC determination and potentiation studies of a fluoroquinolone antibiotic in combination with the isolated compound. Everted membrane vesicles of Escherichia coli cells enriched with NorA were prepared to study efflux inhibitory activity in an isolated manner. RESULTS: The ethanolic extract of Persea lingue was subjected to bioassay guided fractionation and led to the isolation of the known compound kaempferol-3 O-alpha-L-(2,4-bis-E-p-coumaroyl)rhamnoside (compound 1). Evaluation of the dose response relationship of compound 1 showed that ethidium bromide efflux was inhibited, with an IC(50) value of 2 MUM. The positive control, reserpine, was found to have an IC(50) value of 9 MUM. Compound 1 also inhibited NorA in enriched everted membrane vesicles of E. coli. Potentiation studies revealed that compound 1 at 1.56 mg/L synergistically increased the antimicrobial activity of ciprofloxacin 8-fold against a NorA overexpresser, and the synergistic activity was exerted at a fourth of the concentration necessary for reserpine. Compound 1 was not found to exert a synergistic effect on ciprofloxacin against a norA deletion mutant. The 2,3-coumaroyl isomer of compound 1 has been shown previously not to cause acute toxicity in mice at 20 mg/kg/day. CONCLUSIONS: Our results show that compound 1 acts through inhibition of the NorA efflux pump. Combination of compound 1 with subinhibitory concentrations of ciprofloxacin renders a wild type more susceptible and a NorA overexpresser S. aureus susceptible. PMID- 22311937 TI - In vivo activity of thiophene-containing trisubstituted methanes against acute and persistent infection of non-tubercular Mycobacterium fortuitum in a murine infection model. AB - OBJECTIVES: Mycobacterium fortuitum causes opportunist non-tubercular infection in humans. Chronic infection of M. fortuitum has been clinically documented and requires prolonged chemotherapy. The objectives of this study were to characterize acute and persistent infection of M. fortuitum in a murine infection model and to screen thiophene-containing trisubstituted methanes active against both acute and persistent infection. METHODS: A murine infection model of M. fortuitum was used. Bacillary count, bioluminescence, disease symptoms, host immune response, drug susceptibility and mortality were measured. Reactivation of persistent bacilli was induced by dexamethasone. Trisubstituted methanes containing thiophene rings were synthesized and screened in vitro by agar dilution and BACTEC assay and in mice. Cytotoxicity was tested with Vero monkey kidney cells using a resazurin assay. RESULTS: The acute infection in mice was marked by a 3 log rise in viable counts, the appearance of disease symptoms and a rise in the Th1 immune response. Bacilli were susceptible to fluoroquinolones. This was followed by persistent infection, in which disappearance of disease symptoms, a decline in Th1 response and non-susceptibility to fluoroquinolones was observed. When the mice were immunocompromised on day 40 post-infection (persistent state) by dexamethasone, a rise in viable counts, symptoms and susceptibility to fluoroquinolones and a prominent Th1 response reappeared. Two lead compounds were found that cleared the mice of bacilli in acute infection and caused a 2.29-2.99 log reduction in cfu of persistent bacilli. CONCLUSIONS: The study established acute and persistent infection in mice and identified two promising anti-M. fortuitum compounds with a selectivity index >10. PMID- 22311938 TI - Cerebral blood flow abnormalities in neurologically asymptomatic patients with primary antiphospholipid syndrome. AB - OBJECTIVE: To evaluate cerebral blood flow abnormalities in primary antiphospholipid syndrome (PAPS) patients without ongoing neurological manifestations. PATIENTS AND METHODS: We included 28 PAPS patients and 28 healthy controls. Carotid Doppler ultrasound, and echocardiographic evaluation were done. Transcranial Doppler ultrasonography measured mean flow velocity (MFV) in the carotid siphon, middle, anterior, posterior, intracranial vertebral arteries, and basilar artery (11 cerebral arteries). Results were considered abnormal when the MFV was out of the normal range according to age and/or flow asymmetry and/or more than four arterial segments affected. RESULTS: The mean age of patients was 41.4 +/- 11.2 and 39.3 +/- 8.6 years in controls. Disease duration was 11 +/- 2.7 years. A significant increase in MFV in 7/11 cerebral arteries in PAPS patients, mainly in the middle and anterior cerebral arteries was found compared with controls. A significant association between lupus anticoagulant, history of stroke and obesity with a greater number of affected arteries was found. We did not find an association between MFV and abnormal echocardiography, arterial hypertension and carotid intima-media thickness. CONCLUSIONS: Asymptomatic patients with PAPS can have significantly increased MFVs. These alterations may be the consequence of accelerated atherosclerosis, PAPS vasculopathy or both. Whatever the cause, these findings can represent a risk for stroke in PAPS patients that needs the trial of other therapeutic options. PMID- 22311939 TI - Weight loss and improvements in fatigue in systemic lupus erythematosus: a controlled trial of a low glycaemic index diet versus a calorie restricted diet in patients treated with corticosteroids. AB - BACKGROUND: Patients with systemic lupus erythematosus (SLE) may require prolonged periods of corticosteroid therapy which lead to excessive weight gain and increased cardiovascular risk. OBJECTIVE: To assess the utility of a low glycaemic index diet in patients with corticosteroid dependent SLE in achieving weight loss and improving glycaemic control. DESIGN: A total of 23 women were enrolled in a 6 week study. All had mild, stable SLE, were receiving corticosteroids and had a body mass index > 25 kg/m(2). Subjects were randomly assigned to a low glycaemic index (Low GI) diet or a calorie restricted (Low Cal) diet. The primary end point was weight loss. Secondary end points included tolerability of diet, bio-markers of cardiovascular risk, disease activity, fatigue and sleep quality. RESULTS: Weight loss in both treatment groups was significant (mean +/- SD: Low GI diet 3.9 +/- 0.9 kg; Low Cal diet 2.4 +/- 2.2 kg, p < 0.01 from baseline in each group). There were also significant improvements in waist and hip measurements. However, the difference in weight loss and waist and hip measurements between the two diet groups was not statistically significant. There was a statistically significant reduction in Fatigue Severity Scale in both diet groups, (p < 0.03). Both Low GI and Low Cal diets were well tolerated, resulting in no serious adverse effects or increase in disease activity. CONCLUSION: Significant weight loss is achievable over 6 weeks in a diet-specific trial in subjects with stable SLE, who are on low dose prednisolone. Both diets were equally tolerable, and did not cause flares in disease activity. Our results suggest that dietary manipulation may significantly improve fatigue in subjects with SLE. PMID- 22311940 TI - Maternal deaths in women with lupus nephritis: a review of published evidence. AB - BACKGROUND AND OBJECTIVES: Pregnancies in women with systemic lupus erythematosus (SLE) and lupus nephritis are considered high-risk due to high rates of maternal and fetal complications. However, there has not been a formal analysis addressing the issue of maternal deaths in these women. The aim of this study was to perform a literature review of the maternal deaths in women with SLE and lupus nephritis to: (1) identify the main causes of death and (2) discuss possible reasons for these causes, and strategies that may improve patient care and outcomes. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENT: We performed an extensive electronic literature search from 1962 to 2009 using online databases (PubMed, Embase, Lilacs, Cochrane Controlled Trials Register, Medline, and Science Citation Index). Studies were included if they reported pregnancies in patients with SLE and lupus nephritis with at least one reported maternal death. RESULTS: We identified 13 studies that reported a total of 17 deaths in the 6 week post partum period that were attributable to SLE and lupus nephritis. In all cases, death occurred in the setting of active disease, and was attributed either to infection in 41.2% (n = 7), or disease activity in 29.4% (n = 5). The remaining deaths were due to pulmonary embolus in 11.8% (n = 2), pregnancy-associated cardiomyopathy in 5.9% (n = 1), adrenal failure due to abrupt steroid withdrawal in 5.9% (n = 1), and undefined in 5.9% (n = 1). CONCLUSIONS: All maternal deaths in patients with SLE and lupus nephritis occurred in those with active disease, with disease activity/complications and infections (mainly opportunistic) being the two major causes. The presented evidence further supports timing of pregnancy relative to SLE activity, and the judicious use of immunosuppressive agents in pregnant patients. PMID- 22311942 TI - Medical privacy breaches rising. PMID- 22311941 TI - Association of chemokine CXCL12-3'G801A polymorphism with systemic lupus erythematosus in a Han Chinese population. AB - CXCL12, also known as stromal cell-derived factor (SDF-1), is a CXC chemokine. Recent reports have shown that CXCL12 might play key roles in a murine model of lupus and in patients with systemic lupus erythematosus (SLE). A common variant at position 801 in 3'-untranslated region in CXCL12 gene (designated CXCL12 3'G801A) has been reported in association with autoimmune diseases, such as type 1 diabetes and systemic sclerosis. We investigated the influence of CXCL12 3'G801A polymorphism on susceptibility to SLE by genotyping this single nucleotide polymorphism in 422 SLE patients and 374 healthy controls. The frequency of G/G homozygote was observed in 60.0% of SLE patients and in 52.7% of healthy individuals (chi(2 )= 4.275, p = 0.039). Compared with patients with G/A and A/A genotype, SLE patients with G/G genotype were also more prone to developing photosensitivity (chi(2 )= 6.778, p = 0.034), renal damage (chi(2 )= 6.388, p = 0.041) and to producing antibodies against nucleosomes (chi(2 )= 8.341, p = 0.015). Moreover, the plasma level of CXCL12alpha was also significantly increased in patients with G/G homozygote than in healthy controls carrying the same genotype [(4067.0 +/- 1092.3) pg/ml vs. (3278.5 +/- 547.4) pg/ml, p = 0.002]. Our results suggest that polymorphism in CXCL12-3'G801A might be a genetic risk factor for developing SLE. The association of G/G homozygote with nephritis and skin damage developed in SLE patients might be due to its effects upon the production of auto-antibodies and CXCL12 protein. PMID- 22311943 TI - Linear psoriasis. PMID- 22311944 TI - New recommendations for the use of ambulatory blood pressure monitoring in the diagnosis of hypertension. PMID- 22311945 TI - Physicians open to ideas on how to assess and discuss fitness to drive. PMID- 22311946 TI - Physical punishment of children: lessons from 20 years of research. PMID- 22311947 TI - Factors influencing patient choice of dialysis versus conservative care to treat end-stage kidney disease. AB - BACKGROUND: For every patient with chronic kidney disease who undergoes renal replacement therapy, there is one patient who undergoes conservative management of their disease. We aimed to determine the most important characteristics of dialysis and the trade-offs patients were willing to make in choosing dialysis instead of conservative care. METHODS: We conducted a discrete choice experiment involving adults with stage 3-5 chronic kidney disease from eight renal clinics in Australia. We assessed the influence of treatment characteristics (life expectancy, number of visits to the hospital per week, ability to travel, time spent undergoing dialysis [i.e., time spent attached to a dialysis machine per treatment, measured in hours], time of day at which treatment occurred, availability of subsidized transport and flexibility of the treatment schedule) on patients' preferences for dialysis versus conservative care. RESULTS: Of 151 patients invited to participate, 105 completed our survey. Patients were more likely to choose dialysis than conservative care if dialysis involved an increased average life expectancy (odds ratio [OR] 1.84, 95% confidence interval [CI] 1.57-2.15), if they were able to dialyse during the day or evening rather than during the day only (OR 8.95, 95% CI 4.46-17.97), and if subsidized transport was available (OR 1.55, 95% CI 1.24-1.95). Patients were less likely to choose dialysis over conservative care if an increase in the number of visits to hospital was required (OR 0.70, 95% CI 0.56-0.88) and if there were more restrictions on their ability to travel (OR=0.47, 95%CI 0.36-0.61). Patients were willing to forgo 7 months of life expectancy to reduce the number of required visits to hospital and 15 months of life expectancy to increase their ability to travel. INTERPRETATION: Patients approaching end-stage kidney disease are willing to trade considerable life expectancy to reduce the burden and restrictions imposed by dialysis. PMID- 22311948 TI - Managing an expected home death. PMID- 22311949 TI - Recurrent exercise-induced rhabdomyolysis. PMID- 22311951 TI - The rhythms of the Rock. PMID- 22311952 TI - The heartbeat of a First Nation. PMID- 22311953 TI - Yes to ski helmets, but buyer beware. PMID- 22311954 TI - Pay for performance in health care: an international overview of initiatives. AB - Pay for performance (P4P) has become a popular approach to performance improvement in health care. Most of the P4P literature has focused on the United States and there is limited insight in the characteristics of major programs initiated in other countries. This article systematically describes and reviews P4P programs outside the United States. Our literature search identified 13 programs initiated in 9 countries. Although the programs share many similarities, they differ in several important respects, also when compared with the typical P4P program in the United States. In addition, there are clearly possibilities to increase incentive strength and minimize incentives for undesired behavior. In part, observed heterogeneity will be a consequence of contextual differences, but design choices often also seem to be made arbitrarily. In designing their programs, purchasers are hampered by limited knowledge of the influence of specific design choices and effective strategies to mitigate undesired behavior. PMID- 22311955 TI - One fish, two fish, red fish, blue fish: effects of price frames, brand names, and choice set size on Medicare Part D insurance plan decisions. AB - Because many seniors choose Medicare Part D plans offering poorer coverage at greater cost, the authors examined the effect of price frames, brand names, and choice set size on participants' ability to choose the lowest cost plan. A 2*2*2 within-subjects design was used with 126 participants aged 18 to 91 years old. Mouselab, a web-based program, allowed participants to choose drug plans across eight trials that varied using numeric or symbolic prices, real or fictitious drug plan names, and three or nine drug plan options. Results from the multilevel models suggest numeric versus symbolic prices decreased the likelihood of choosing the lowest cost plan (-8.0 percentage points, 95% confidence interval= 14.7 to -0.9). The likelihood of choosing the lowest cost plan decreased as the amount of information increased suggesting that decision cues operated independently and collectively when selecting a drug plan. Redesigning the current Medicare Part D plan decision environment could improve seniors' drug plan choices. PMID- 22311956 TI - Immigration and contract problems experienced by foreign-educated nurses. AB - More than 8% of employed RNs licensed since 2004 in the United States were educated overseas, yet little is known about the conditions of their recruitment or the impact of that experience on health care practice. This study assessed whether the labor rights of foreign-educated nurses were at risk during the latest period of high international recruitment: 2003 to 2007. Using consensus based standards contained in the Voluntary Code of Ethical Conduct for the Recruitment of Foreign-Educated Health Professionals to the United States, this study found 50% of actively recruited foreign-educated nurses experienced a negative recruitment practice. The study also found that nurses educated in low income countries and nurses with high contract breach fees, were significantly more likely to report such problems. If, as experts believe may occur, the nursing shortage in the United States returns around 2014, oversight of international recruitment will become critically important to delivering high quality health care to Americans. PMID- 22311957 TI - Variation in long-term acute care hospital use after intensive care. AB - Long-term acute care hospitals (LTACs) are an increasingly common discharge destination for patients recovering from intensive care. In this article the authors use U.S. Medicare claims data to examine regional- and hospital-level variation in LTAC utilization after intensive care to determine factors associated with their use. Using hierarchical regression models to control for patient characteristics, this study found wide variation in LTAC utilization across hospitals, even controlling for LTAC access within a region. Several hospital characteristics were independently associated with increasing LTAC utilization, including increasing hospital size, for-profit ownership, academic teaching status, and colocation of the LTAC within an acute care hospital. These findings highlight the need for research into LTAC admission criteria and the incentives driving variation in LTAC utilization across hospitals. PMID- 22311958 TI - Youth opinions of tobacco control in New Zealand: support for specific measures and the relationship with smoking behaviors among 14-15-year-olds. AB - INTRODUCTION: The purpose of this study was to assess the attitudes of young people toward tobacco control and explore the association between these attitudes and both smoking intentions and behavior. METHODS: The study used data from a national survey of 14- and 15-year-old students in New Zealand (NZ) investigating tobacco use and attitudes. Attitudes to tobacco control were assessed using student responses to 7 statements relating to specific tobacco control measures; outdoor smoking bans, increased and hypothecated tax, display bans, plain packaging, and reduced access. Analysis was conducted on a final sample of 24,495 students aged 14-15 years. Chi-square testing was used to determine group differences in smoking status and attitudes toward tobacco control measures, while logistic regression was used to test associations between youth attitudes and both smoking susceptibility and current smoking. RESULTS: Our results demonstrate youth support for tobacco control interventions in NZ. Commercial access measures received the most support, while plain packaging and display bans were the least supported measures among young people. Young people's attitudes toward tobacco control measures were found to be associated with smoking behavior; those who were opposed to measures were more likely to be susceptible to smoking or be current smokers. CONCLUSIONS: Young people in NZ have opinions when it comes to tobacco control, and it is important to investigate these when developing tobacco control policies that are aimed to have an effect on this demographic. The results provide evidence to support the proposed "end game" strategies currently being considered in NZ. PMID- 22311959 TI - Temporal and probability discounting by cigarette smokers following acute smoking abstinence. AB - INTRODUCTION: Given the lack of consensus regarding changes in temporal and probability discounting as a function of smoking abstinence in cigarette smokers, the present study comprehensively examined possible changes in these processes following a period of acute smoking abstinence consistent with elevated withdrawal symptoms and craving. METHODS: Computerized temporal and probability discounting assessments were collected from cigarette smokers following normal smoking and 24-hr smoking abstinence, with the order of normal smoking and abstinence sessions counterbalanced across participants. Other conditions included commodity (money and cigarettes), sign (gains and losses), and magnitude ($50 and $1,000). RESULTS: Twenty four-hour smoking abstinence resulted in a reduction in expired carbon monoxide to near-zero levels and increases in withdrawal and craving. Examination of discounting parameters as a function of smoking abstinence revealed a general pattern of increase in the temporal discounting of monetary gains and losses following abstinence but not in the temporal discounting of cigarettes nor probability discounting of money or cigarettes. Pearson correlations also revealed an expected pattern of significant relationships. CONCLUSIONS: The present study is a comprehensive examination of temporal and probability discounting following smoking abstinence and reveals a generalized change in intertemporal decision making for monetary rewards. PMID- 22311960 TI - Randomized controlled trial evaluation of a tailored leaflet and SMS text message self-help intervention for pregnant smokers (MiQuit). AB - INTRODUCTION: Study aims were to assess the feasibility and acceptability of a tailored self-help smoking cessation intervention for pregnant smokers (MiQuit). Secondary aims were to assess whether MiQuit affected cognitive determinants of quitting and to provide a range of potential effect sizes of the intervention effect on smoking abstinence. METHODS: A randomized controlled trial was undertaken in which pregnant smokers were allocated to either receive MiQuit, a tailored self-help leaflet followed by an 11-week program of tailored text messages, or to a control group, receiving a nontailored self-help leaflet. Participants were 207 pregnant smokers identified by community midwives across 7 NHS Trusts (United Kingdom). At 3-month follow-up, intervention acceptability, cognitive determinants of quitting, and smoking outcomes (self-reported and cotinine-validated 7-day point prevalence abstinence) were assessed. RESULTS: Feasibility: 94% (95% CI 89%-99%) of MiQuit participants reported receiving both intervention components. Acceptability: 9% (95% CI 4%-15%) of MiQuit participants opted to discontinue the text messages. Mechanism: compared with controls, MiQuit participants were more likely to set a quit date (p = .049) and reported higher levels of self-efficacy (p = .024), harm beliefs (p = .052), and determination to quit (p = .019). Potential efficacy: self-reported abstinence-MiQuit 22.9%, control 19.6%; odds ratio (OR) = 1.22, 95% CI 0.62-2.41; cotinine-validated abstinence-MiQuit 12.5%, control 7.8%; OR = 1.68, 95% CI 0.66-4.31. CONCLUSIONS: Delivering tailored smoking cessation support to pregnant smokers via leaflet and text message is feasible and acceptable. The positive effects of MiQuit on cognitive determinants and the likelihood of setting a quit date are encouraging. A larger efficacy trial is warranted. PMID- 22311961 TI - Effect of menthol on nicotine pharmacokinetics in rats after cigarette smoke inhalation. AB - INTRODUCTION: The effect of menthol on nicotine disposition is important in understanding smoking behaviors among different racial groups. The present study was to evaluate whether menthol affects the pharmacokinetics of nicotine after cigarette smoke inhalation. METHODS: Rats were exposed to mainstream smoke from either a nonmentholated or mentholated cigarette (1 puff/min for 10 min) using a smoke inhalation apparatus. For the multiple-cigarette smoke inhalation, rats received the smoke from either nonmentholated or mentholated cigarette (10 puffs) every 12 hr for a total of 17 cigarettes. Serial blood samples were collected during the 10-min inhalation phase for the single-cigarette smoke or the 17th cigarette inhalation and for 30 hr thereafter. Nicotine and its major metabolite cotinine were assayed by radioimmunoassay methods. RESULTS: Following single cigarette smoke inhalation, mentholated cigarettes significantly decreased the mean peak concentrations of nicotine in plasma (C(max)) from 27.1 to 9.61 ng/ml and the total area under the plasma concentration-time curves (AUC) from 977 to 391 ng min/ml as compared with those after nonmentholated cigarette smoke inhalation. C(max) and AUC values for cotinine were also significantly reduced by menthol. Similarly after multiple smoke inhalation, C(max), AUC, and the mean average steady-state plasma concentration of nicotine as well as cotinine were significantly lower in mentholated cigarette inhalation. Interestingly, there was a significant increase in the cotinine to nicotine AUC ratio from 13.8 for the nonmentholated to 21.1 for the mentholated cigarette. CONCLUSIONS: These results suggest that menthol in mentholated cigarettes can substantially decrease the absorption and/or increase the clearance of nicotine. PMID- 22311962 TI - Electronic cigarettes: effective nicotine delivery after acute administration. AB - INTRODUCTION: Electronic cigarettes (ECs) are marketed as nicotine delivery devices. Two studies with EC-naive participants suggest that ECs deliver little or no nicotine. In those studies, standard-sized ECs were used, though experienced EC users often use larger devices that house higher voltage and/or longer lasting batteries. Whether user experience and device characteristics influence EC nicotine delivery is uncertain. The purpose of the present study was to examine the effects of ECs in experienced users who were using their preferred devices. METHODS: Eight EC users (3 women) who had been using ECs for at least 3 months, completed one 5-hr session using devices they provided and the flavor/strength nicotine cartridges they selected. Sessions consisted of 4 phases: baseline, 10 puffs (30-s interpuff interval) from the device, 1-hr ad lib puffing period, and a 2-hr rest period (no puffing). Outcome measures in each phase included plasma nicotine concentration, heart rate, and subjective ratings of nicotine/product effects and abstinence symptoms. RESULTS: Relative to baseline, plasma nicotine and heart rate increased significantly within 5 min of the first puff and remained elevated throughout the ad lib puffing period. Increases in ratings of direct effects of nicotine and product were observed as well as decreases in abstinence symptoms. CONCLUSIONS: User experience and/or device characteristics likely influence EC nicotine delivery and other effects. Systematic manipulation of these and other variables could elucidate conditions that produce intended effects. PMID- 22311963 TI - Stability of cigarette consumption over time among continuing smokers: a latent growth curve analysis. AB - OBJECTIVES: This paper examined the stability over time of daily cigarette consumption of continuing smokers and explored factors that might account for the patterns of change in consumption using a latent growth curve (LGC) analytic approach. METHODS: Data come from the first 5 waves of the International Tobacco Control Four-Country Survey, conducted in Canada, the United States, the United Kingdom, and Australia where a cohort of over 2,000 smokers from each country were recruited and followed up annually with replenishment. RESULTS: Raw data revealed that continuing smokers showed a marked steep decline in cigarettes per day during the first 2 waves followed by a gentler linear decline in consumption over the remaining waves of the study period. This pattern of change in cigarette consumption was best modelled using a piecewise linear LGC model. Baseline consumption level was highest in Australia and lowest in the United Kingdom, although the rate of decline was similar across the 4 countries. Being older than 55 years and having made at least 1 quit attempt were related to greater rate of decline in consumption. CONCLUSIONS: Continuing smokers who are unwilling or unable to quit smoking can and do attempt to reduce their daily cigarette consumption over time. Factors such as making a quit attempt even if unsuccessful and experiencing smoking bans at work and at homes can contribute to reduced smoking among this group, which suggests that interventions focusing in on these factors, along with providing cessation help, may greatly improve their chances of quitting smoking altogether. PMID- 22311964 TI - Ethnic differences in patterns of secondhand smoke exposure among adolescents in Israel. AB - INTRODUCTION: Adolescent secondhand smoke exposure (SHSe) is associated with smoking initiation and independently damages health. METHODS: We used data from the school-based 2003-2004 Israel National Health and Nutrition Youth survey (MABAT) to examine patterns and determinants of SHSe in a multiethnic sample of Israeli adolescents. School and child response rates were high (school: 91.8%, child: 87.9%), with 6,274 participants. We used generalized estimating equations to examine SHSe determinants. RESULTS: Most Israeli adolescents were exposed to SHS (total: 85.6%; home: 40%; school: 31.4%; entertainment: 73.3%; other: 16.3%). Exposure patterns differed between the Jewish and non-Jewish sectors. Jews were more frequently exposed at school and entertainment venues than were non-Jews but were less frequently exposed at home. Druze were the least exposed and non-Arab Christians the most exposed. Secular Jews were more exposed than were religious Jews; the opposite was true among Arabs. Children of less-educated fathers were exposed more than children of more-educated fathers. Adolescents who smoked were more exposed than were nonsmokers. CONCLUSIONS: The high levels of SHSe among Israeli adolescents were characterized by different patterns of exposure among different population groups. Interventions to reduce adolescent SHSe, with appropriate tailoring, are urgently needed. These findings provide support for sustainable implementation of the recent governmentally approved tobacco control plan, which includes extended legislation for, and increased enforcement of, laws about smoking bans in schools and entertainment venues. Researchers elsewhere should be aware that levels and patterns of SHSe may vary greatly by subpopulation. PMID- 22311965 TI - Physiology without borders 2. PMID- 22311966 TI - Slc13a1 and Slc26a1 KO models reveal physiological roles of anion transporters. AB - Anion transporters NaS1 (SLC13A1) and Sat1 (SLC26A1) mediate sulfate (re)absorption across renal proximal tubule and small intestinal epithelia, thereby regulating blood sulfate levels. Disruption of murine NaS1 and Sat1 genes leads to hyposulfatemia and hypersulfaturia. Sat1-null mice also exhibit hyperoxalemia, hyperoxaluria, and calcium oxalate urolithiasis. This review will highlight the current pathophysiological features of NaS1- and Sat1-null mice resulting from alterations in circulating sulfate and oxalate anion levels. PMID- 22311967 TI - New insights into molecular players involved in neurotransmitter release. AB - The strength of a synapse can profoundly influence network function. How this strength is set at the molecular level is a key question in neuroscience. Here, we review a simple model of neurotransmission that serves as a convenient framework to discuss recent studies on RIM and synaptotagmin. PMID- 22311968 TI - Structures of usher syndrome 1 proteins and their complexes. AB - Usher syndrome 1 (USH1) is the most common and severe form of hereditary loss of hearing and vision. Genetic, physiological, and cell biological studies, together with recent structural investigations, have not only uncovered the physiological functions of the five USH1 proteins but also provided mechanistic explanations for the hearing and visual deficiencies in humans caused by USH1 mutations. This review focuses on the structural basis of the USH1 protein complex organization. PMID- 22311969 TI - Novel Ser/Thr protein phosphatases in cell death regulation. AB - Cell death is regulated by a myriad of intracellular molecular pathways, with many involving protein phosphorylation and dephosphorylation. In this review, we will focus on Ser/Thr phosphatases-mediated regulation in cell apoptosis as well as on their potential roles in cell necrosis. The emerging functional importance of Ser/Thr protein phosphatases in cell death regulation adds new dimension to the signaling mechanisms of cellular function, physiology, and diseases. PMID- 22311970 TI - Human protein N-terminal acetyltransferase hNaa50p (hNAT5/hSAN) follows ordered sequential catalytic mechanism: combined kinetic and NMR study. AB - N(alpha)-acetylation is a common protein modification catalyzed by different N terminal acetyltransferases (NATs). Their essential role in the biogenesis and degradation of proteins is becoming increasingly evident. The NAT hNaa50p preferentially modifies peptides starting with methionine followed by a hydrophobic amino acid. hNaa50p also possesses N(epsilon)-autoacetylation activity. So far, no eukaryotic NAT has been mechanistically investigated. In this study, we used NMR spectroscopy, bisubstrate kinetic assays, and product inhibition experiments to demonstrate that hNaa50p utilizes an ordered Bi Bi reaction of the Theorell-Chance type. The NMR results, both the substrate binding study and the dynamic data, further indicate that the binding of acetyl-CoA induces a conformational change that is required for the peptide to bind to the active site. In support of an ordered Bi Bi reaction mechanism, addition of peptide in the absence of acetyl-CoA did not alter the structure of the protein. This model is further strengthened by the NMR results using a catalytically inactive hNaa50p mutant. PMID- 22311971 TI - Insights into O-linked N-acetylglucosamine ([0-9]O-GlcNAc) processing and dynamics through kinetic analysis of O-GlcNAc transferase and O-GlcNAcase activity on protein substrates. AB - Cellular O-linked N-acetylglucosamine (O-GlcNAc) levels are modulated by two enzymes: uridine diphosphate-N-acetyl-D-glucosamine:polypeptidyltransferase (OGT) and O-GlcNAcase (OGA). To quantitatively address the activity of these enzymes on protein substrates, we generated five structurally diverse proteins in both unmodified and O-GlcNAc-modified states. We found a remarkably invariant upper limit for k(cat)/K(m) values for human OGA (hOGA)-catalyzed processing of these modified proteins, which suggests that hOGA processing is driven by the GlcNAc moiety and is independent of the protein. Human OGT (hOGT) activity ranged more widely, by up to 15-fold, suggesting that hOGT is the senior partner in fine tuning protein O-GlcNAc levels. This was supported by the observation that K(m,app) values for UDP-GlcNAc varied considerably (from 1 MUM to over 20 MUM), depending on the protein substrate, suggesting that some OGT substrates will be nutrient-responsive, whereas others are constitutively modified. The ratios of k(cat)/K(m) values obtained from hOGT and hOGA kinetic studies enable a prediction of the dynamic equilibrium position of O-GlcNAc levels that can be recapitulated in vitro and suggest the relative O-GlcNAc stoichiometries of target proteins in the absence of other factors. We show that changes in the specific activities of hOGT and hOGA measured in vitro on calcium/calmodulin dependent kinase IV (CaMKIV) and its pseudophosphorylated form can account for previously reported changes in CaMKIV O-GlcNAc levels observed in cells. These studies provide kinetic evidence for the interplay between O-GlcNAc and phosphorylation on proteins and indicate that these effects can be mediated by changes in hOGT and hOGA kinetic activity. PMID- 22311972 TI - Loss of transcription factor nuclear factor-erythroid 2 (NF-E2) p45-related factor-2 (Nrf2) leads to dysregulation of immune functions, redox homeostasis, and intracellular signaling in dendritic cells. AB - Dendritic cells (DCs) are critical mediators of immunity and immune tolerance by orchestrating multiple aspects of T cell activation and function. Immature DCs (iDCs) expressing low levels of co-stimulatory receptors are highly efficient at antigen capture but are poor activators of T cells. Maturation of DCs is associated with increased expression of co-stimulatory molecules. Co-stimulatory receptor gene expression is regulated by intracellular redox, NF-kappaB, and MAPK pathways and by histone deacetylase (HDAC) activity. The transcription factor, Nrf2, is important for maintaining intracellular glutathione (GSH) levels and redox homeostasis and has been implicated in modulating DC co-stimulatory receptor expression. It is unclear whether Nrf2 mediates this effect by GSH dependent mechanisms and whether it influences DC signaling pathways. Using bone marrow-derived iDCs from Nrf2(+/+) and Nrf2(-/-) mice, we demonstrate that Nrf2( /-) iDCs have lower basal GSH levels, enhanced co-stimulatory receptor expression, impaired phagocytic functions, and increased antigen-specific CD8 T cell stimulation capacity. Interestingly, lowering GSH levels in Nrf2(+/+) iDCs did not recapitulate the Nrf2(-/-) iDC phenotype. Loss of Nrf2 resulted in elevated basal levels of reactive oxygen species but did not affect basal NF kappaB activity or p38 MAPK phosphorylation. Using pharmacological inhibitors, we demonstrate that enhanced co-stimulatory receptor phenotype of Nrf2(-/-) iDC does not require ERK activity but is dependent on HDAC activity, indicating a potential interaction between Nrf2 function and HDAC. These results suggest that Nrf2 activity is required to counter rises in intracellular reactive oxygen species and to regulate pathways that control DC co-stimulatory receptor expression. PMID- 22311973 TI - Toxin-induced RhoA activity mediates CCL1-triggered signal transducers and activators of transcription protein signaling. AB - RhoA is reportedly involved in signal transducers and activators of transcription (STAT)-dependent transcription. However, the pathway connecting the GTPase and STAT signaling has not been characterized. Here, we made use of bacterial toxins, which directly activate Rho GTPases to analyze this pathway. Cytotoxic necrotizing factors (CNFs) are produced by pathogenic Escherichia coli strains and by Yersinia pseudotuberculosis. They activate small GTPases of the Rho family by deamidation of a glutamine, which is crucial for GTP hydrolysis. We show that RhoA activation leads to phosphorylation and activation of STAT3 and identify signal proteins involved in this pathway. RhoA-dependent STAT3 stimulation requires ROCK and Jun kinase activation as well as AP1-induced protein synthesis. The secretion of one or more factors activates the JAK-STAT pathway in an auto/paracrine manner. We identify CCL1/I-309 as an essential cytokine, which is produced and secreted upon RhoA activation and which is able to activate STAT3 dependent signaling pathways. PMID- 22311974 TI - Reactive oxygen species and mitochondrial sensitivity to oxidative stress determine induction of cancer cell death by p21. AB - p21(Waf1/Cip1/Sdi1) is a cyclin-dependent kinase inhibitor that mediates cell cycle arrest. Prolonged p21 up-regulation induces a senescent phenotype in normal and cancer cells, accompanied by an increase in intracellular reactive oxygen species (ROS). However, it has been shown recently that p21 expression can also lead to cell death in certain models. The mechanisms involved in this process are not fully understood. Here, we describe an induction of apoptosis by p21 in sarcoma cell lines that is p53-independent and can be ameliorated with antioxidants. Similar levels of p21 and ROS caused senescence in the absence of significant death in other cancer cell lines, suggesting a cell-specific response. We also found that cells undergoing p21-dependent cell death had higher sensitivity to oxidants and a specific pattern of mitochondrial polarization changes. Consistent with this, apoptosis could be blocked with targeted expression of catalase in the mitochondria of these cells. We propose that the balance between cancer cell death and arrest after p21 up-regulation depends on the specific effects of p21-induced ROS on the mitochondria. This suggests that selective up-regulation of p21 in cancer cells could be a successful therapeutic intervention for sarcomas and tumors with lower resistance to mitochondrial oxidative damage, regardless of p53 status. PMID- 22311975 TI - Structure of protein having inhibitory disintegrin and leukotriene scavenging functions contained in single domain. AB - The antihemostatic/antiangiogenic protein tablysin-15 is a member of the CAP (cysteine-rich secretory, antigen 5, and pathogenesis-related 1 protein) superfamily and has been shown to bind the integrins alpha(IIb)beta(3) and alpha(V)beta(3) by means of an Arg-Gly-Asp (RGD) tripeptide sequence. Here we describe the x-ray crystal structure of tablysin-15 and show that the RGD motif is located in a novel structural context. The motif itself is contained in a type II beta-turn structure that is similar in its conformation to the RGD sequence of the cyclic pentapeptide cilengitide when bound to integrin alpha(V)beta(3). The CAP domain also contains a hydrophobic channel that appears to bind a fatty acid molecule in the crystal structure after purification from Escherichia coli. After delipidation of the protein, tablysin-15 was found to bind proinflammatory cysteinyl leukotrienes with submicromolar affinities. The structure of the leukotriene E(4)-tablysin-15 complex shows that the ligand binds with the nonfunctionalized end of the fatty acid chain buried in the hydrophobic pocket, whereas the carboxylate end of the ligand binds forms hydrogen bond/salt bridge interactions with polar side chains at the channel entrance. Therefore, tablysin 15 functions as an inhibitor of integrin function and as an anti-inflammatory scavenger of eicosanoids. PMID- 22311976 TI - Role of Derlin-1 protein in proteostasis regulation of ATP-sensitive potassium channels. AB - ATP-sensitive potassium (K(ATP)) channels composed of sulfonylurea receptor 1 (SUR1) and Kir6.2 regulate insulin secretion by linking glucose metabolism with membrane potential. The number of K(ATP) channels in the plasma membrane affects the sensitivity of beta-cells to glucose. Aberrant surface channel expression leads to insulin secretion disease. Previously, we have shown that K(ATP) channel proteins undergo endoplasmic reticulum (ER)-associated degradation (ERAD) via the ubiquitin-proteasome pathway, and inhibition of proteasome function results in an increase in channel surface expression. Here, we investigated whether Derlin-1, a protein involved in retrotranslocation of misfolded or misassembled proteins across the ER membrane for degradation by cytosolic proteasomes, plays a role in ERAD and, in turn, biogenesis efficiency of K(ATP) channels. We show that both SUR1 and Kir6.2 form a complex with Derlin-1 and an associated AAA-ATPase, p97. Overexpression of Derlin-1 led to a decrease in the biogenesis efficiency and surface expression of K(ATP) channels. Conversely, knockdown of Derlin-1 by RNA interference resulted in increased processing of SUR1 and a corresponding increase in surface expression of K(ATP) channels. Importantly, knockdown of Derlin-1 increased the abundance of disease-causing misfolded SUR1 or Kir6.2 proteins and even partially rescued surface expression in a mutant channel. We conclude that Derlin-1, by being involved in ERAD of SUR1 and Kir6.2, has a role in modulating the biogenesis efficiency and surface expression of K(ATP) channels. The results suggest that physiological or pathological changes in Derlin-1 expression levels may affect glucose-stimulated insulin secretion by altering surface expression of K(ATP) channels. PMID- 22311977 TI - Lack of evidence for presenilins as endoplasmic reticulum Ca2+ leak channels. AB - Familial Alzheimer disease (FAD) is linked to mutations in the presenilin (PS) homologs. FAD mutant PS expression has several cellular consequences, including exaggerated intracellular Ca(2+) ([Ca(2+)](i)) signaling due to enhanced agonist sensitivity and increased magnitude of [Ca(2+)](i) signals. The mechanisms underlying these phenomena remain controversial. It has been proposed that PSs are constitutively active, passive endoplasmic reticulum (ER) Ca(2+) leak channels and that FAD PS mutations disrupt this function resulting in ER store overfilling that increases the driving force for release upon ER Ca(2+) release channel opening. To investigate this hypothesis, we employed multiple Ca(2+) imaging protocols and indicators to directly measure ER Ca(2+) dynamics in several cell systems. However, we did not observe consistent evidence that PSs act as ER Ca(2+) leak channels. Nevertheless, we confirmed observations made using indirect measurements employed in previous reports that proposed this hypothesis. Specifically, cells lacking PS or expressing a FAD-linked PS mutation displayed increased area under the ionomycin-induced [Ca(2+)](i) versus time curve (AI) compared with cells expressing WT PS. However, an ER-targeted Ca(2+) indicator revealed that this did not reflect overloaded ER stores. Monensin pretreatment selectively attenuated the AI in cells lacking PS or expressing a FAD PS allele. These findings contradict the hypothesis that PSs form ER Ca(2+) leak channels and highlight the need to use ER-targeted Ca(2+) indicators when studying ER Ca(2+) dynamics. PMID- 22311978 TI - Cytotoxic mechanism of selenomethionine in yeast. AB - Although selenium is an essential element, its excessive uptake is detrimental to living organisms. The significance of selenium for living organisms has been exploited for various purposes. However, the molecular basis of selenium toxicity is not completely understood. Here, we applied a capillary electrophoresis time of-flight mass spectrometry-based metabolomics approach to analysis of yeast cells treated with selenomethionine. The data indicated that intracellular thiol compounds are significantly decreased, and diselenide and selenosulfide compounds are increased in selenomethionine-treated cells. The growth defect induced by selenomethionine was recovered by extracellular addition of cysteine and by genetic modification of yeast cells that have an additional de novo synthetic pathway for cysteine. Because cysteine is an intermediate of thiol compounds, these results suggested that the loss of a reduced form of thiol compounds due to selenomethionine causes a growth defect of yeast cells. PMID- 22311979 TI - Ezrin-radixin-moesin-binding sequence of PSGL-1 glycoprotein regulates leukocyte rolling on selectins and activation of extracellular signal-regulated kinases. AB - P-selectin glycoprotein ligand-1 (PSGL-1) mediates the capture (tethering) of free-flowing leukocytes and subsequent rolling on selectins. PSGL-1 interactions with endothelial selectins activate Src kinases and spleen tyrosine kinase (Syk), leading to alpha(L)beta(2) integrin-dependent leukocyte slow rolling, which promotes leukocyte recruitment into tissues. In addition, but through a distinct pathway, PSGL-1 engagement activates ERK. Because ezrin, radixin and moesin proteins (ERMs) link PSGL-1 to actin cytoskeleton and because they serve as adaptor molecules between PSGL-1 and Syk, we examined the role of PSGL-1 ERM binding sequence (EBS) on cell capture, rolling, and signaling through Syk and MAPK pathways. We carried out mutational analysis and observed that deletion of EBS severely reduced 32D leukocyte tethering and rolling on L-, P-, and E selectin and slightly increased rolling velocity. Alanine substitution of Arg-337 and Lys-338 showed that these residues play a key role in supporting leukocyte tethering and rolling on selectins. Importantly, EBS deletion or Arg-337 and Lys 338 mutations abrogated PSGL-1-induced ERK activation, whereas they did not prevent Syk phosphorylation or E-selectin-induced leukocyte slow rolling. These studies demonstrate that PSGL-1 EBS plays a critical role in recruiting leukocytes on selectins and in activating the MAPK pathway, whereas it is dispensable to phosphorylate Syk and to lead to alpha(L)beta(2)-dependent leukocyte slow rolling. PMID- 22311980 TI - Arogenate dehydratase isoenzymes profoundly and differentially modulate carbon flux into lignins. AB - How carbon flux differentially occurs in vascular plants following photosynthesis for protein formation, phenylpropanoid metabolism (i.e. lignins), and other metabolic processes is not well understood. Our previous discovery/deduction that a six-membered arogenate dehydratase (ADT1-6) gene family encodes the final step in Phe biosynthesis in Arabidopsis thaliana raised the fascinating question whether individual ADT isoenzymes (or combinations thereof) differentially modulated carbon flux to lignins, proteins, etc. If so, unlike all other lignin pathway manipulations that target cell wall/cytosolic processes, this would be the first example of a plastid (chloroplast)-associated metabolic process influencing cell wall formation. Homozygous T-DNA insertion lines were thus obtained for five of the six ADTs and used to generate double, triple, and quadruple knockouts (KOs) in different combinations. The various mutants so obtained gave phenotypes with profound but distinct reductions in lignin amounts, encompassing a range spanning from near wild type levels to reductions of up to ~68%. In the various KOs, there were also marked changes in guaiacyl:syringyl ratios ranging from ~3:1 to 1:1, respectively; these changes were attributed to differential carbon flux into vascular bundles versus that into fiber cells. Laser microscope dissection/pyrolysis GC/MS, histochemical staining/lignin analyses, and pADT::GUS localization indicated that ADT5 preferentially affects carbon flux into the vascular bundles, whereas the adt3456 knock-out additionally greatly reduced carbon flux into fiber cells. This plastid-localized metabolic step can thus profoundly differentially affect carbon flux into lignins in distinct anatomical regions and provides incisive new insight into different factors affecting guaiacyl:syringyl ratios and lignin primary structure. PMID- 22311981 TI - Protein phosphatase 1alpha mediates ceramide-induced ERM protein dephosphorylation: a novel mechanism independent of phosphatidylinositol 4, 5 biphosphate (PIP2) and myosin/ERM phosphatase. AB - ERM (ezrin, radixin, and moesin) proteins are cytoskeletal interacting proteins that bind cortical actin, the plasma membrane, and membrane proteins, which are found in specialized plasma membrane structures such as microvilli and filopodia. ERM proteins are regulated by phosphatidylinositol 4, 5-biphosphate (PIP(2)) and by phosphorylation of a C-terminal threonine, and its inactivation involves PIP(2) hydrolysis and/or myosin phosphatase (MP). Recently, we demonstrated that ERM proteins are also subject to counter regulation by the bioactive sphingolipids ceramide and sphingosine 1-phosphate. Plasma membrane ceramide induces ERM dephosphorylation whereas sphingosine 1-phosphate induces their phosphorylation. In this work, we pursue the mechanisms by which ceramide regulates dephosphorylation. We found that this dephosphorylation was independent of hydrolysis and localization of PIP(2) and MP. However, the results show that ERM dephosphorylation was blocked by treatment with protein phosphatase 1 (PP1) pharmacological inhibitors and specifically by siRNA to PP1alpha, whereas okadaic acid, a PP2A inhibitor, failed. Moreover, a catalytic inactive mutant of PP1alpha acted as dominant negative of the endogenous PP1alpha. Additional results showed that the ceramide mechanism of PP1alpha activation is largely independent of PIP(2) hydrolysis and MP. Taken together, these results demonstrate a novel, acute mechanism of ERM regulation dependent on PP1alpha and plasma membrane ceramide. PMID- 22311982 TI - Augmentation of Kv4.2-encoded currents by accessory dipeptidyl peptidase 6 and 10 subunits reflects selective cell surface Kv4.2 protein stabilization. AB - Rapidly activating and inactivating somatodendritic voltage-gated K(+) (Kv) currents, I(A), play critical roles in the regulation of neuronal excitability. Considerable evidence suggests that native neuronal I(A) channels function in macromolecular protein complexes comprising pore-forming (alpha) subunits of the Kv4 subfamily together with cytosolic, K(+) channel interacting proteins (KChIPs) and transmembrane, dipeptidyl peptidase 6 and 10 (DPP6/10) accessory subunits, as well as other accessory and regulatory proteins. Several recent studies have demonstrated a critical role for the KChIP subunits in the generation of native Kv4.2-encoded channels and that Kv4.2-KChIP complex formation results in mutual (Kv4.2-KChIP) protein stabilization. The results of the experiments here, however, demonstrate that expression of DPP6 in the mouse cortex is unaffected by the targeted deletion of Kv4.2 and/or Kv4.3. Further experiments revealed that heterologously expressed DPP6 and DPP10 localize to the cell surface in the absence of Kv4.2, and that co-expression with Kv4.2 does not affect total or cell surface DPP6 or DPP10 protein levels. In the presence of DPP6 or DPP10, however, cell surface Kv4.2 protein expression is selectively increased. Further addition of KChIP3 in the presence of DPP10 markedly increases total and cell surface Kv4.2 protein levels, compared with cells expressing only Kv4.2 and DPP10. Taken together, the results presented here demonstrate that the expression and localization of the DPP accessory subunits are independent of Kv4 alpha subunits and further that the DPP6/10 and KChIP accessory subunits independently stabilize the surface expression of Kv4.2. PMID- 22311983 TI - Pannexin 1, an ATP release channel, is activated by caspase cleavage of its pore associated C-terminal autoinhibitory region. AB - Pannexin 1 (PANX1) channels mediate release of ATP, a "find-me" signal that recruits macrophages to apoptotic cells; PANX1 activation during apoptosis requires caspase-mediated cleavage of PANX1 at its C terminus, but how the C terminus inhibits basal channel activity is not understood. Here, we provide evidence suggesting that the C terminus interacts with the human PANX1 (hPANX1) pore and that cleavage-mediated channel activation requires disruption of this inhibitory interaction. Basally silent hPANX1 channels localized on the cell membrane could be activated directly by protease-mediated C-terminal cleavage, without additional apoptotic effectors. By serial deletion, we identified a C terminal region just distal to the caspase cleavage site that is required for inhibition of hPANX1; point mutations within this small region resulted in partial activation of full-length hPANX1. Consistent with the C-terminal tail functioning as a pore blocker, we found that truncated and constitutively active hPANX1 channels could be inhibited, in trans, by the isolated hPANX1 C terminus either in cells or when applied directly as a purified peptide in inside-out patch recordings. Furthermore, using a cysteine cross-linking approach, we showed that relief of inhibition following cleavage requires dissociation of the C terminus from the channel pore. Collectively, these data suggest a mechanism of hPANX1 channel regulation whereby the intact, pore-associated C terminus inhibits the full-length hPANX1 channel and a remarkably well placed caspase cleavage site allows effective removal of key inhibitory C-terminal determinants to activate hPANX1. PMID- 22311984 TI - Phospholipase C-related but catalytically inactive protein (PRIP) modulates synaptosomal-associated protein 25 (SNAP-25) phosphorylation and exocytosis. AB - Exocytosis is one of the most fundamental cellular events. The basic mechanism of the final step, membrane fusion, is mediated by the formation of the SNARE complex, which is modulated by the phosphorylation of proteins controlled by the concerted actions of protein kinases and phosphatases. We have previously shown that a protein phosphatase-1 (PP1) anchoring protein, phospholipase C-related but catalytically inactive protein (PRIP), has an inhibitory role in regulated exocytosis. The current study investigated the involvement of PRIP in the phospho dependent modulation of exocytosis. Dephosphorylation of synaptosome-associated protein of 25 kDa (SNAP-25) was mainly catalyzed by PP1, and the process was modulated by wild-type PRIP but not by the mutant (F97A) lacking PP1 binding ability in in vitro studies. We then examined the role of PRIP in phospho dependent regulation of exocytosis in cell-based studies using pheochromocytoma cell line PC12 cells, which secrete noradrenalin. Exogenous expression of PRIP accelerated the dephosphorylation process of phosphorylated SNAP-25 after forskolin or phorbol ester treatment of the cells. The phospho-states of SNAP-25 were correlated with noradrenalin secretion, which was enhanced by forskolin or phorbol ester treatment and modulated by PRIP expression in PC12 cells. Both SNAP 25 and PP1 were co-precipitated in anti-PRIP immunocomplex isolated from PC12 cells expressing PRIP. Collectively, together with our previous observation regarding the roles of PRIP in PP1 regulation, these results suggest that PRIP is involved in the regulation of the phospho-states of SNAP-25 by modulating the activity of PP1, thus regulating exocytosis. PMID- 22311985 TI - Identification of NIPSNAP1 as a nocistatin-interacting protein involving pain transmission. AB - 4-Nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1) is a molecule of physiologically unknown function, although it is predominantly expressed in the brain, spinal cord, liver, and kidney. We identified NIPSNAP1 as a protein that interacts with the neuropeptide nocistatin (NST) from synaptosomal membranes of mouse spinal cord using high-performance affinity latex beads. NST, which is produced from the same precursor protein as an opioid-like neuropeptide nociceptin/orphanin FQ (N/OFQ), has opposite effects on pain transmission evoked by N/OFQ. The calculated full-length pre-protein of NIPSNAP1 was 33 kDa, whereas the N-terminal truncated form of NIPSNAP1 (29 kDa) was ubiquitously expressed in the neuronal tissues, especially in synaptic membrane and mitochondria of brain. The 29-kDa NIPSNAP1 was distributed on the cell surface, and NST interacted with the 29-kDa but not the 33-kDa NIPSNAP1. Although intrathecal injection of N/OFQ induced tactile allodynia in both wild type and NIPSNAP1-deficient mice, the inhibition of N/OFQ-evoked tactile allodynia by NST seen in wild-type mice was completely lacking in the deficient mice. These results suggest that NIPSNAP1 is an interacting molecule of NST and plays a crucial role in pain transmission. PMID- 22311986 TI - Remodeling of lipid droplets during lipolysis and growth in adipocytes. AB - Synthesis, storage, and turnover of triacylglycerols (TAGs) in adipocytes are critical cellular processes to maintain lipid and energy homeostasis in mammals. TAGs are stored in metabolically highly dynamic lipid droplets (LDs), which are believed to undergo fragmentation and fusion under lipolytic and lipogenic conditions, respectively. Time lapse fluorescence microscopy showed that stimulation of lipolysis in 3T3-L1 adipocytes causes progressive shrinkage and almost complete degradation of all cellular LDs but without any detectable fragmentation into micro-LDs (mLDs). However, mLDs were rapidly formed after induction of lipolysis in the absence of BSA in the culture medium that acts as a fatty acid scavenger. Moreover, mLD formation was blocked by the acyl-CoA synthetase inhibitor triacsin C, implicating that mLDs are synthesized de novo in response to cellular fatty acid overload. Using label-free coherent anti-Stokes Raman scattering microscopy, we demonstrate that LDs grow by transfer of lipids from one organelle to another. Notably, this lipid transfer between closely associated LDs is not a rapid and spontaneous process but rather occurs over several h and does not appear to require physical interaction over large LD surface areas. These data indicate that LD growth is a highly regulated process leading to the heterogeneous LD size distribution within and between individual cells. Our findings suggest that lipolysis and lipogenesis occur in parallel in a cell to prevent cellular fatty acid overflow. Furthermore, we propose that formation of large LDs requires a yet uncharacterized protein machinery mediating LD interaction and lipid transfer. PMID- 22311987 TI - Discovery of marinopyrrole A (maritoclax) as a selective Mcl-1 antagonist that overcomes ABT-737 resistance by binding to and targeting Mcl-1 for proteasomal degradation. AB - The anti-apoptotic Bcl-2 family of proteins, including Bcl-2, Bcl-X(L) and Mcl-1, are well-validated drug targets for cancer treatment. Several small molecules have been designed to interfere with Bcl-2 and its fellow pro-survival family members. While ABT-737 and its orally active analog ABT-263 are the most potent and specific inhibitors to date that bind Bcl-2 and Bcl-X(L) with high affinity but have a much lower affinity for Mcl-1, they are not very effective as single agents in certain cancer types because of elevated levels of Mcl-1. Accordingly, compounds that specifically target Mcl-1 may overcome this resistance. In this study, we identified and characterized the natural product marinopyrrole A as a novel Mcl-1-specific inhibitor and named it maritoclax. We found that maritoclax binds to Mcl-1, but not Bcl-X(L), and is able to disrupt the interaction between Bim and Mcl-1. Moreover, maritoclax induces Mcl-1 degradation via the proteasome system, which is associated with the pro-apoptotic activity of maritoclax. Importantly, maritoclax selectively kills Mcl-1-dependent, but not Bcl-2- or Bcl X(L)-dependent, leukemia cells and markedly enhances the efficacy of ABT-737 against hematologic malignancies, including K562, Raji, and multidrug-resistant HL60/VCR, by ~60- to 2000-fold at 1-2 MUM. Taken together, these results suggest that maritoclax represents a new class of Mcl-1 inhibitors, which antagonizes Mcl 1 and overcomes ABT-737 resistance by targeting Mcl-1 for degradation. PMID- 22311989 TI - Good outcome with early empiric treatment of neural larva migrans due to Baylisascaris procyonis. AB - We report a remarkably good outcome in a 14-month-old boy with early clinical diagnosis and aggressive empirical treatment of neural larva migrans caused by the raccoon roundworm Baylisascaris procyonis. He presented with fever, meningismus, lethargy, irritability and asymmetric spastic extremity weakness. Early findings of marked blood and cerebrospinal fluid eosinophilia and of diffuse white matter signal abnormality in the brain and spinal cord on MRI suggested a parasitic encephalomyelitis. Rapid presumptive treatment with albendazole and high-dose steroids halted progression of clinical signs. The diagnosis was confirmed by 2 sequential enzyme-linked immunosorbent assay studies positive for B procyonis serum immunoglobulin G and by Western blot. Field examination with soil sampling yielded infective Baylisascaris eggs. Repeat MRI 3 months later showed atrophy and diffuse, chronic white matter abnormalities, discordant with the marked clinical improvement in this interval. At 10 months, residual neurologic deficits included subtle paraparesis and moderate language delay. This case is the first in which spinal involvement in human Baylisascaris infection was clinically suspected and confirmed by neuroimaging. Importantly, early diagnosis and aggressive treatment of Baylisascaris meningo-encephalitis and myelitis with albendazole and high-dose steroids likely contributed to the good outcome in this patient, in contrast with previous reports. PMID- 22311988 TI - Early childhood family intervention and long-term obesity prevention among high risk minority youth. AB - OBJECTIVES: To test the hypothesis that family intervention to promote effective parenting in early childhood affects obesity in preadolescence. METHODS: Participants were 186 minority youth at risk for behavior problems who enrolled in long-term follow-up studies after random assignment to family intervention or control condition at age 4. Follow-up Study 1 included 40 girls at familial risk for behavior problems; Follow-up Study 2 included 146 boys and girls at risk for behavior problems based on teacher ratings. Family intervention aimed to promote effective parenting and prevent behavior problems during early childhood; it did not focus on physical health. BMI and health behaviors were measured an average of 5 years after intervention in Study 1 and 3 years after intervention in Study 2. RESULTS: Youth randomized to intervention had significantly lower BMI at follow-up relative to controls (Study 1 P = .05; Study 2 P = .006). Clinical impact is evidenced by lower rates of obesity (BMI >=95th percentile) among intervention girls and boys relative to controls (Study 2: 24% vs 54%, P = .002). There were significant intervention-control group differences on physical and sedentary activity, blood pressure, and diet. CONCLUSIONS: Two long-term follow up studies of randomized trials show that relative to controls, youth at risk for behavior problems who received family intervention at age 4 had lower BMI and improved health behaviors as they approached adolescence. Efforts to promote effective parenting and prevent behavior problems early in life may contribute to the reduction of obesity and health disparities. PMID- 22311990 TI - Growth and development in a child with resistance to thyroid hormone and ectopic thyroid gland. AB - Resistance to thyroid hormone is an uncommon problem, which has rarely been associated with thyroid dysgenesis. We report a case with both thyroid gland ectopy and resistance to thyroid hormone and, thus, a reduced capacity to produce and respond to thyroid hormone. The patient presented at 2 years of age with developmental delay, dysmorphic features, and elevation in both thyroxine and thyrotropin. We document her response to therapy with thyroxine, with particular regard to her growth and development. Persistent elevation of thyrotropin is commonly recognized during treatment of congenital hypothyroidism. Resistance to thyroid hormone may be an important additional diagnosis to consider in cases where thyrotropin remains persistently elevated. PMID- 22311991 TI - End-of-life decisions in abusive head trauma. AB - Abusive head trauma is a significant and tragic cause of morbidity and mortality in infants and its victims often have a poor prognosis. With such high rates of morbidity and mortality, health care providers and parents are often faced with the decision to continue or discontinue life support for an affected child. Sadly, however, this decision becomes complicated when parents are accused of causing the victim-child's current state. In this situation, if life support is withdrawn, criminal charges for the accused may escalate from assault to murder. This escalation of legal charges creates a conflict of interest for accused parents. As a result, parents have a strong incentive to avoid murder charges by using their parental decision-making rights to keep the child alive, even when treatment is deemed futile or inhumane. In this article, we discuss the legal challenges health care providers may face when parents place their interest above their child's. We also propose solutions that give greater deference to the rights and interest of these critically ill children while still preserving protected parental rights. PMID- 22311992 TI - Secondhand smoke exposure in cars among middle and high school students--United States, 2000-2009. AB - OBJECTIVES: Exposure to secondhand smoke (SHS) from cigarettes poses a significant health risk to nonsmokers. Among youth, the home is the primary source of SHS. However, little is known about youth exposure to SHS in other nonpublic areas, particularly motor vehicles. METHODS: Data were obtained from the 2000, 2002, 2004, 2006, and 2009 waves of the National Youth Tobacco Survey, a nationally representative survey of US students in grades 6 to 12. Trends in SHS exposure in a car were assessed across survey years by school level, gender, and race/ethnicity by using binary logistic regression. RESULTS: From 2000 to 2009, the prevalence of SHS exposure in cars declined significantly among both nonsmokers (39.0%-22.8%; trend P < .001) and smokers (82.3%-75.3%; trend P < .001). Among nonsmokers, this decline occurred across all school level, gender, and race/ethnicity subgroups. CONCLUSIONS: SHS exposure in cars decreased significantly among US middle and high school students from 2000 to 2009. Nevertheless, in 2009, over one-fifth of nonsmoking students were exposed to SHS in cars. Jurisdictions should expand comprehensive smoke-free policies that prohibit smoking in worksites and public places to also prohibit smoking in motor vehicles occupied by youth. PMID- 22311993 TI - Prospective analysis of pulmonary hypertension in extremely low birth weight infants. AB - OBJECTIVES: Pulmonary hypertension is associated with bronchopulmonary dysplasia in extremely low birth weight (ELBW) infants and contributes to morbidity and mortality. The objective was to determine the prevalence of pulmonary hypertension among ELBW infants by screening echocardiography and evaluate subsequent outcomes. METHODS: All ELBW infants admitted to a regional perinatal center were evaluated for pulmonary hypertension with echocardiography at 4 weeks of age and subsequently if clinical signs suggestive of right-sided heart failure or severe lung disease were evident. Management was at discretion of the clinician, and infants were evaluated until discharge from the hospital or pre discharge death occurred. RESULTS: One hundred forty-five ELBW infants (birth weight: 755 +/- 144 g; median gestational age: 26 weeks [interquartile range: 24 27]) were screened from December 2008 to February 2011. Overall, 26 (17.9%) were diagnosed with pulmonary hypertension at any time during hospitalization (birth weight: 665 +/- 140 g; median gestational age: 26 weeks [interquartile range: 24 27]): 9 (6.2%) by initial screening (early pulmonary hypertension) and 17 (11.7%) who were identified later (late pulmonary hypertension). Infants with pulmonary hypertension were more likely to receive oxygen treatment on day 28 compared with those without pulmonary hypertension (96% vs 75%, P < .05). Of the 26 infants, 3 died (all in the late group because of cor pulmonale) before being discharged from the hospital. CONCLUSIONS: Pulmonary hypertension is relatively common, affecting at least 1 in 6 ELBW infants, and persists to discharge in most survivors. Routine screening of ELBW infants with echocardiography at 4 weeks of age identifies only one-third of the infants diagnosed with pulmonary hypertension. Further research is required to determine optimal detection and intervention strategies. PMID- 22311994 TI - Thrombotic microangiopathy and Purtscher-like retinopathy as a rare presentation of juvenile dermatomyositis. AB - Juvenile dermatomyositis is a rare systemic vasculopathy that may sometimes present with acute complications. We report here the case of a 7-year-old boy with severe dermatomyositis associated with thrombocytopenia and blurry vision. The presence of schistocytosis and the secondary occurrence of hemolytic anemia were consistent with a diagnosis of thrombotic thrombocytopenic purpura (TTP). Further investigations demonstrated the association of TTP with muscular microangiopathy and Purtscher-like retinopathy. Retinal and hematologic involvements dramatically improved after the initiation of plasma exchange in emergency. This report emphasizes that early recognition of TTP and prompt plasmapheresis are important in a child with severe juvenile dermatomyositis associated with thrombocytopenia. PMID- 22311995 TI - Resilience in children undergoing stem cell transplantation: results of a complementary intervention trial. AB - BACKGROUND: Children undergoing stem cell transplantation (SCT) are thought to be at risk for increased distress, adjustment difficulties, and impaired health related quality of life (HRQL). We report results of a multisite trial designed to improve psychological adjustment and HRQL in children undergoing SCT. METHODS: A total of 171 patients and parents from 4 sites were randomized to receive a child-targeted intervention; a child and parent intervention; or standard care. The child intervention included massage and humor therapy; the parent intervention included massage and relaxation/imagery. Outcomes included symptoms of depression and posttraumatic stress, HRQL, and benefit finding. Assessments were conducted by patient and parent report at admission and SCT week+24. RESULTS: Across the sample, significant improvements were seen on all outcomes from admission to week+24. Surprisingly, patients who had SCT reported low levels of adjustment difficulties at admission, and improved to normative or better than average levels of adjustment and HRQL at week+24. Benefit finding was high at admission and increased at week+24; however, there were no statistically significant differences between intervention arms for any of the measures. CONCLUSIONS: Although the results do not support the benefits of these complementary interventions in pediatric SCT, this may be explained by the remarkably positive overall adjustment seen in this sample. Improvements in supportive care, and a tendency for patients to find benefit in the SCT experience, serve to promote positive outcomes in children undergoing this procedure, who appear particularly resilient to the challenge. PMID- 22311996 TI - Macrolide treatment failure in streptococcal pharyngitis resulting in acute rheumatic fever. AB - Macrolide resistance (MR) in group A Streptococcus (GAS) has been well documented in several countries and has become clinically significant since the large increases in macrolide usage during the 1970s. Macrolides are recommended as an alternative therapy for GAS pharyngitis, the most common cause of bacterial pharyngitis. Macrolide resistance has been associated with certain emm types, a sequence-based typing system of the hypervariable region of the GAS M-protein gene. Clinical failure of macrolide treatment of GAS infections can be associated with complications including acute rheumatic fever and rheumatic heart disease, the leading cause of acquired heart disease in children worldwide. Here we report 2 pediatric cases of MR and/or treatment failure in the treatment of GAS pharyngitis with the subsequent development of acute rheumatic fever. We also review the literature on worldwide MR rates, molecular classifications, and emm types, primarily associated with GAS pharyngeal isolates between the years of 2000 and 2010. The use of macrolides in the management of GAS pharyngitis should be limited to patients with significant penicillin allergy. PMID- 22311997 TI - The effect of simulated ostracism on physical activity behavior in children. AB - OBJECTIVES: To assess the effects of simulated ostracism on children's physical activity behavior, time allocated to sedentary behavior, and liking of physical activity. METHODS: Nineteen children (11 boys, 8 girls; age 11.7 +/- 1.3 years) completed 2 experimental sessions. During each session, children played a virtual ball-toss computer game (Cyberball). In one session, children played Cyberball and experienced ostracism; in the other session, they were exposed to the inclusion/control condition. The order of conditions was randomized. After playing Cyberball, children were taken to a gymnasium where they had free-choice access to physical and sedentary activities for 30 minutes. Children could participate in the activities, in any pattern they chose, for the entire period. Physical activity during the free-choice period was assessed via accelerometery and sedentary time via observation. Finally, children reported their liking for the activity session via a visual analog scale. RESULTS: Children accumulated 22% fewer (P < .01) accelerometer counts and 41% more (P < .04) minutes of sedentary activity in the ostracized condition (8.9(e+4) +/- 4.5(e+4) counts, 11.1 +/- 9.3 minutes) relative to the included condition (10.8(e+4) +/- 4.7(e+4) counts, 7.9 +/- 7.9 minutes). Liking (8.8 +/- 1.5 cm included, 8.1 +/- 1.9 cm ostracized) of the activity sessions was not significantly different (P > .10) between conditions. CONCLUSIONS: Simulated ostracism elicits decreased subsequent physical activity participation in children. Ostracism may contribute to children's lack of physical activity. PMID- 22311998 TI - Pediatric training and career intentions, 2003-2009. AB - OBJECTIVES: To examine trends in pediatric residents' training and job search experiences from 2003 through 2009. METHODS: Annual national random samples of 500 graduating pediatric residents from 2003 through 2005 and 1000 from 2006 through 2009 were surveyed. Responses were compared across years to identify trends. We examined resident demographics, training, satisfaction, career intentions, and job search experiences. Overall response rate was 61%. RESULTS: Between 2003 and 2009, there was an increase in the proportion of female graduating pediatric residents (69%-75%), residents from international medical schools (15%-23%), and levels of educational debt among the subgroup of residents with debt ($139 945 in 2003 to $166 972 in 2009). Residents consistently reported (>90% of residents) that they would choose pediatrics again if they had the choice. By 2009, the majority was very satisfied with the quality of their training in most areas, with ratings improving across years in caring for children with special health care needs, evidence-based medicine, and using information technology in practice. Although primary care remained the most common clinical practice goal, there was a modest decline in interest in primary care practice across survey years, whereas interest in subspecialty practice increased. Residents accepting both general pediatric practice and hospitalist positions reported less difficulty in their job search over time. CONCLUSIONS: Despite continually changing demographics of pediatric training programs, residents overall remain very satisfied with their decision to become pediatricians. Pediatricians continue to face difficult financial challenges associated with rising debt, but they also report increasing job search success. PMID- 22311999 TI - Using US data to estimate the incidence of serious physical abuse in children. AB - BACKGROUND: There are limited data on the epidemiology of serious injuries due to physical abuse of children. METHODS: We used the 2006 Kids' Inpatient Database to estimate the incidence of hospitalizations due to serious physical abuse among children <18 years of age. Abuse was defined by using International Classification of Diseases, Ninth Revision, Clinical Modification codes for injuries (800-959) and for physical abuse (995.50, 995.54, 995.55, or 995.59), selected assault codes (E960-966, 968), or child battering (E967). We examined demographic characteristics, mean costs, and length of stay in 3 groups of hospitalized children: abusive injuries, nonabusive injuries, and all other reasons for hospitalization. Incidence was calculated using the weighted number of cases of physical abuse and the number of children at risk based on 2006 intercensal data. RESULTS: The weighted number of cases due to abuse was 4569; the incidence was 6.2 (95% confidence interval [CI]: 5.5-6.9) per 100 000 children <18 years of age. The incidence was highest in children <1 year of age (58.2 per 100 000; 95% CI: 51.0-65.3) and even higher in infants covered by Medicaid (133.1 per 100 000; 95% CI: 115.2-151.0 [or 1 in 752 infants]). Overall, there were 300 children who died in the hospital due to physical abuse. CONCLUSIONS: This is the first study to provide national US data on the occurrence of serious injuries due to physical abuse in hospitalized children. Data from the 2006 Kids' Inpatient Database on hospitalizations due to serious physical abuse can be used to track trends over time and the effects of prevention programs on serious physical abuse. PMID- 22312000 TI - The population cost-effectiveness of interventions designed to prevent childhood depression. AB - BACKGROUND AND OBJECTIVES: Depression in childhood and adolescence is common and often persists into adulthood. This study assessed the population-level cost effectiveness of a preventive intervention that screens children and adolescents for symptoms of depression in schools and the subsequent provision of a psychological intervention to those showing elevated signs of depression. The target population for screening comprised 11- to 17-year-old children and adolescents in the 2003 Australian population. METHODS: Economic modeling techniques were used to assess the incremental cost-effectiveness of the intervention compared with no intervention. The perspective was that of the health sector, and outcomes were measured by using disability-adjusted life-years (DALYs). Multivariate probabilistic and univariate sensitivity testing was applied to quantify variations in the model parameters. RESULTS: The modeled psychological intervention had an incremental cost-effectiveness ratio of $5400 per DALY averted, with just 2% of iterations falling above a $50 000 per DALY value-for-money threshold. Results were robust to model assumptions. CONCLUSIONS: After school screening, screening and the psychological intervention represent good value-for-money. Such an intervention needs to be seriously considered in any national package of preventive health services. Acceptability issues, particularly to intervention providers, including schools and mental health professionals, need to be considered before wide-scale adoption. PMID- 22312001 TI - Pamela Silver: synthesizing a new biology. Interview by Caitlin Sedwick. PMID- 22312002 TI - Organelle segregation during mitosis: lessons from asymmetrically dividing cells. AB - Studies on cell division traditionally focus on the mechanisms of chromosome segregation and cytokinesis, yet we know comparatively little about how organelles segregate. Analysis of organelle partitioning in asymmetrically dividing cells has provided insights into the mechanisms through which cells control organelle distribution. Interestingly, these studies have revealed that segregation mechanisms frequently link organelle distribution to organelle growth and formation. Furthermore, in many cases, cells use organelles, such as the endoplasmic reticulum and P granules, as vectors for the segregation of information. Together, these emerging data suggest that the coordination between organelle growth, division, and segregation plays an important role in the control of cell fate inheritance, cellular aging, and rejuvenation, i.e., the resetting of age in immortal lineages. PMID- 22312003 TI - Inhibition of pyrimidine synthesis reverses viral virulence factor-mediated block of mRNA nuclear export. AB - The NS1 protein of influenza virus is a major virulence factor essential for virus replication, as it redirects the host cell to promote viral protein expression. NS1 inhibits cellular messenger ribonucleic acid (mRNA) processing and export, down-regulating host gene expression and enhancing viral gene expression. We report in this paper the identification of a nontoxic quinoline carboxylic acid that reverts the inhibition of mRNA nuclear export by NS1, in the absence or presence of the virus. This quinoline carboxylic acid directly inhibited dihydroorotate dehydrogenase (DHODH), a host enzyme required for de novo pyrimidine biosynthesis, and partially reduced pyrimidine levels. This effect induced NXF1 expression, which promoted mRNA nuclear export in the presence of NS1. The release of NS1-mediated mRNA export block by DHODH inhibition also occurred in the presence of vesicular stomatitis virus M (matrix) protein, another viral inhibitor of mRNA export. This reversal of mRNA export block allowed expression of antiviral factors. Thus, pyrimidines play a necessary role in the inhibition of mRNA nuclear export by virulence factors. PMID- 22312004 TI - FoxO limits microtubule stability and is itself negatively regulated by microtubule disruption. AB - Transcription factors are essential for regulating neuronal microtubules (MTs) during development and after axon damage. In this paper, we identify a novel neuronal function for Drosophila melanogaster FoxO in limiting MT stability at the neuromuscular junction (NMJ). foxO loss-of-function NMJs displayed augmented MT stability. In contrast, motor neuronal overexpression of wild-type FoxO moderately destabilized MTs, whereas overexpression of constitutively nuclear FoxO severely destabilized MTs. Thus, FoxO negatively regulates synaptic MT stability. FoxO family members are well-established components of stress activated feedback loops. We hypothesized that FoxO might also be regulated by cytoskeletal stress because it was well situated to shape neuronal MT organization after cytoskeletal damage. Indeed, levels of neuronal FoxO were strongly reduced after acute pharmacological MT disruption as well as sustained genetic disruption of the neuronal cytoskeleton. This decrease was independent of the dual leucine zipper kinase-Wallenda pathway and required function of Akt kinase. We present a model wherein FoxO degradation is a component of a stabilizing, protective response to cytoskeletal insult. PMID- 22312005 TI - Siliques are Red1 from Arabidopsis acts as a bidirectional amino acid transporter that is crucial for the amino acid homeostasis of siliques. AB - Many membrane proteins are involved in the transport of nutrients in plants. While the import of amino acids into plant cells is, in principle, well understood, their export has been insufficiently described. Here, we present the identification and characterization of the membrane protein Siliques Are Red1 (SIAR1) from Arabidopsis (Arabidopsis thaliana) that is able to translocate amino acids bidirectionally into as well as out of the cell. Analyses in yeast and oocytes suggest a SIAR1-mediated export of amino acids. In Arabidopsis, SIAR1 localizes to the plasma membrane and is expressed in the vascular tissue, in the pericycle, in stamen, and in the chalazal seed coat of ovules and developing seeds. Mutant alleles of SIAR1 accumulate anthocyanins as a symptom of reduced amino acid content in the early stages of silique development. Our data demonstrate that the SIAR1-mediated export of amino acids plays an important role in organic nitrogen allocation and particularly in amino acid homeostasis in developing siliques. PMID- 22312006 TI - SCARECROW has a SHORT-ROOT-independent role in modulating the sugar response. AB - Sugar is essential for all cellular activities, but at high levels it inhibits growth and development. How plants balance the tradeoffs between the need for sugars and their growth inhibitory effects is poorly understood. SHORT-ROOT (SHR) and SCARECROW (SCR) are key regulators of stem cell renewal and radial patterning in the root of Arabidopsis (Arabidopsis thaliana). Recently, we identified direct targets of SHR at the genome scale. Intriguingly, among the top-ranked list, we found a number of genes that are involved in stress responses. By chromatin immunoprecipitation-polymerase chain reaction (PCR), we showed that SHR and SCR regulate a similar but not identical set of stress response genes. Consistent with this, scr and shr were found to be hypersensitive to abscisic acid (ABA). We further showed that both mutants were hypersensitive to high levels of glucose (Glc) but responded normally to high salinity and osmoticum. The endogenous levels of sucrose, Glc, and fructose were also elevated in shr and scr. Intriguingly, although shr had sugar content and developmental defects similar to those of scr, it was much less sensitive to Glc. Chromatin immunoprecipitation PCR and reverse transcription-PCR assays as well as transgenic studies with an ABA-INSENSITIVE2 (ABI4)-beta-glucuronidase reporter construct revealed that in root, SCR, but not SHR, repressed ABI4 and ABI5 directly and specifically in the apical meristem. When combined with abi4, scr became much more tolerant of high Glc. Finally, transgenic plants expressing ABI4 under the control of the SCR promoter manifested a short-root phenotype. These results together suggest that SCR has a SHR-independent role in mitigating the sugar response and that this role of SCR is important for root growth. PMID- 22312007 TI - Effects of neutralizing antibodies to interferon beta in multiple sclerosis: a logical paradox. PMID- 22312008 TI - Epidemiology in multiple sclerosis has had its day: there are no more unanswered questions--yes. PMID- 22312009 TI - Risk stratification for progressive multifocal leukoencephalopathy in patients treated with natalizumab. AB - Natalizumab is a highly effective immunomodulator in the treatment of multiple sclerosis (MS). Treatment with natalizumab has been associated with progressive multifocal leukoencephalopathy (PML), an infection of the central nervous system (CNS) caused by a pathogenic form of the normally benign JC virus (JCV). We searched PubMed and used current data from the natalizumab global safety database to assess risk factors and quantify the risk of PML. Natalizumab treatment duration and prior use of immunosuppressive therapies are established risk factors for development of PML in natalizumab-treated patients. With the development of a reliable and validated assay for detection of antibodies in patients with MS directed against JCV, it is now possible to identify persons who are carriers of JCV. The availability of this assay provides an additional option for risk stratification of PML in patients using or considering natalizumab therapy. Recommendations for clinical management of patients with MS and use of natalizumab are provided based on the presence of these three risk factors. The identification of risk factors that increase the likelihood of PML in natalizumab treated patients can facilitate benefit-risk discussions between health care professionals and patients. Continued research and data collection will further develop our understanding of PML and the mechanisms by which these risk factors contribute to its development. PMID- 22312010 TI - Defining the palliative care patient: a systematic review. AB - BACKGROUND: The lack of a clear definition of the palliative care patient hampers the comparison of results across different studies and impedes implementation of research findings in everyday practice. AIM: The aim of this article is to propose minimum characteristics that define a palliative care patient. DESIGN: The design involved a systematic review of medical literature searching randomised controlled trials (RCTs) in palliative care for clear descriptions of their palliative care patients. We systematically describe relevant characteristics of the study populations of 60 eligible RCTs. DATA SOURCES: The data sources used were MEDLINE, EMBASE, CINAHL, and PSYCHINFO, including all non cancer RCTs (1 January 1995-4 March 2010) and an equivalent number of the most recent cancer RCTs (1 January 2003-4 March 2010). RESULTS: Half of the non-cancer studies were excluded because they did not relate to palliative care. We conclude that published RCTs have no clear definitions of their palliative care patients and illustrate the diversity of this patient, the lack of consensus concerning the attributes of illnesses needing palliation and the ambiguous use of the adjective 'palliative'. CONCLUSIONS: We propose elements of the patients' health status (e.g. a progressive, life-threatening disease with no possibility of obtaining remission or stabilisation, or modifying the course of the illness) and the care delivered to them (e.g. a holistic interdisciplinary approach that focuses on supporting the quality of the end of life) to be included in the definition of a palliative care patient. We also suggest considering the patients' readiness to accept palliative care and a vision of palliative care shared by the patient and all caregivers involved as potentially important elements in this definition. PMID- 22312011 TI - Cross cultural equivalence testing of the Prosthetic Evaluation Questionnaire (PEQ) for an Arabic speaking population. AB - BACKGROUND: There are currently no published prosthetic-related outcome measurement tools (OMT) available in the Arabic language. OBJECTIVE: The aim of this study was to translate the Prosthetic Evaluation Questionnaire (PEQ) into Arabic, ensuring cross-cultural equivalence with the original English language version. STUDY DESIGN: Psychometric property testing. METHODS: The PEQ was culturally and linguistically adapted from English to Arabic using a process of forward translation, backward translation, committee review and pre-testing. Pre testing was carried out in a clinical trial where subjects each completed the questionnaire in Arabic and English, and underwent random probe questioning. The data were compared and analysed, using intraclass correlation (ICC) and Bland Altman plots. RESULTS: Seven patients gave consent and completed the study. For all nine PEQ scales, the ICC point estimate scores were above 0.8, indicating a good degree of correlation. However, for some scales, the 95% confidence interval was wide, indicating a large level of variation. The Bland Altman plots displayed a good distribution around the mean for most of the scales, although the results were affected by the small sample size. CONCLUSION: The results of the analysis showed that the Arabic version of the PEQ was linguistically equivalent to the original version, although further testing with a larger sample group is recommended. CLINICAL RELEVANCE: The availability of a prosthetic outcome measurement tool in Arabic will enable clinicians to collect evidence that can be used to monitor and improve patient care. As there is currently little information available about amputees in the Gulf region, this tool will be a useful resource to both clinicians and decision makers. PMID- 22312012 TI - Does pulsatile perfusion improve outcome after cardiac surgery? A propensity matched analysis of 1959 patients. AB - OBJECTIVE: We analyzed the influence of pulsatile perfusion on recovery after coronary bypass grafting (CABG) or aortic valve replacement (AVR). PATIENTS AND METHODS: Between January 2008 and December 2010, 1959 consecutive patients underwent CABG, AVR, or both. The choice for pulsatile perfusion (PP, n=220) or non-pulsatile perfusion (NPP, n=1739) was made by the surgeon. Patient propensity score to receive PP or NPP was calculated according to 15 preoperative variables. Resulting propensity scores, logistic EuroSCORE, perfusion type and surgeon were analyzed to evaluate their role for mortality, length of postoperative ICU and hospital stay (LOHS), transfusion requirements and renal function. Risk stratified non-parametric univariate analyses and propensity adjusted multivariate analyses were performed. RESULTS: EuroSCORE and hospital mortality did not differ significantly between PP and NPP. EuroSCORE was the best predictive factor for all examined variables (p<0.001). PP was superior concerning LOHS (p=0.019) and this benefit increased with higher logistic EuroSCORE. The surgeon significantly influenced ventilation time, ICU stay and transfusion requirements. CONCLUSION: Pulsatile perfusion did not influence perioperative outcome parameters, renal function and mortality, but resulted in shorter hospital stay, especially in critically ill patients. PMID- 22312013 TI - A critical role for muscle ring finger-1 in acute lung injury-associated skeletal muscle wasting. AB - RATIONALE: Acute lung injury (ALI) is a debilitating condition associated with severe skeletal muscle weakness that persists in humans long after lung injury has resolved. The molecular mechanisms underlying this condition are unknown. OBJECTIVES: To identify the muscle-specific molecular mechanisms responsible for muscle wasting in a mouse model of ALI. METHODS: Changes in skeletal muscle weight, fiber size, in vivo contractile performance, and expression of mRNAs and proteins encoding muscle atrophy-associated genes for muscle ring finger-1 (MuRF1) and atrogin1 were measured. Genetic inactivation of MuRF1 or electroporation-mediated transduction of miRNA-based short hairpin RNAs targeting either MuRF1 or atrogin1 were used to identify their role in ALI-associated skeletal muscle wasting. MEASUREMENTS AND MAIN RESULTS: Mice with ALI developed profound muscle atrophy and preferential loss of muscle contractile proteins associated with reduced muscle function in vivo. Although mRNA expression of the muscle-specific ubiquitin ligases, MuRF1 and atrogin1, was increased in ALI mice, only MuRF1 protein levels were up-regulated. Consistent with these changes, suppression of MuRF1 by genetic or biochemical approaches prevented muscle fiber atrophy, whereas suppression of atrogin1 expression was without effect. Despite resolution of lung injury and down-regulation of MuRF1 and atrogin1, force generation in ALI mice remained suppressed. CONCLUSIONS: These data show that MuRF1 is responsible for mediating muscle atrophy that occurs during the period of active lung injury in ALI mice and that, as in humans, skeletal muscle dysfunction persists despite resolution of lung injury. PMID- 22312014 TI - Activation of mitochondrial biogenesis by heme oxygenase-1-mediated NF-E2-related factor-2 induction rescues mice from lethal Staphylococcus aureus sepsis. AB - RATIONALE: Mitochondrial damage is an important component of multiple organ failure syndrome, a highly lethal complication of severe sepsis that lacks specific therapy. Mitochondrial quality control is regulated in part by the heme oxygenase-1 (HO-1; Hmox1) system through the redox-regulated NF-E2-related factor 2 (Nrf2) transcription factor, but its role in mitochondrial biogenesis in Staphylococcus aureus sepsis is unknown. OBJECTIVES: To test the hypothesis that Nrf2-dependent up-regulation of the HO-1/carbon monoxide (CO) system would preserve mitochondrial biogenesis and rescue mice from lethal S. aureus sepsis. METHODS: A controlled murine S. aureus peritonitis model with and without inhaled CO was examined for HO-1 and Nrf2 regulation of mitochondrial biogenesis and the resolution of hepatic mitochondrial damage. MEASUREMENTS AND MAIN RESULTS: Sepsis survival was significantly enhanced using inhaled CO (250 ppm once-daily for 1 h), and linked mechanistically to Hmox1 induction and mitochondrial HO activity through Nrf2 transcriptional and Akt kinase activity. HO-1/CO stimulated Nrf2 dependent gene expression and nuclear accumulation of nuclear respiratory factor 1, -2alpha (Gabpa), and peroxisome proliferator-activated receptor gamma coactivator-1alpha; increased mitochondrial transcription factor-A and citrate synthase protein levels; and augmented mtDNA copy number. CO enhanced antiinflammatory IL-10 and reduced proinflammatory tumor necrosis factor-alpha production. By contrast, Nrf2(-/-) and Akt1(-/-) mice lacked CO induction of Hmox1 and mitochondrial biogenesis, and CO rescued neither strain from S. aureus sepsis. CONCLUSIONS: We identify an inducible Nrf2/HO-1 regulatory cycle for mitochondrial biogenesis that is prosurvival and counter-inflammatory in sepsis, and describe targeted induction of mitochondrial biogenesis as a potential multiple organ failure therapy. PMID- 22312015 TI - Breastfeeding and lung function at school age: does maternal asthma modify the effect? AB - RATIONALE: The evidence for an effect of breastfeeding on lung function is conflicting, in particular whether the effect is modified by maternal asthma. OBJECTIVES: To explore the association between breastfeeding and school-age lung function. METHODS: In the Leicestershire Cohort Studies we assessed duration of breastfeeding (not breastfed, <=3 months, 4-6 months, and >6 months), other exposures, and respiratory symptoms by repeated questionnaires. Post bronchodilator FVC, FEV(1), peak expiratory flow (PEF), forced midexpiratory flow (FEF(50)), and skin prick tests were measured at age 12 years. We performed multivariable linear regression and tested potential causal pathways (N = 1,458). MEASUREMENTS AND MAIN RESULTS: In the entire sample, FEF(50) was higher by 130 and 164 ml in children breastfed for 4 to 6 months and longer than 6 months, respectively, compared with those not breastfed (P = 0.048 and 0.041), with larger effects if the mother had asthma. FVC and FEV(1) were associated with breastfeeding only in children of mothers with asthma (P for interaction, 0.018 and 0.008): FVC was increased by 123 and 164 ml for those breastfed 4 to 6 months or longer than 6 months, respectively (P = 0.177 and 0.040) and FEV(1) was increased by 148 and 167 ml, respectively (P = 0.050 and 0.016). Results were unchanged after adjustment for respiratory infections in infancy and asthma and atopy in the child. CONCLUSIONS: In this cohort, breastfeeding for more than 4 months was associated with increased FEF(50) and, in children of mothers with asthma, with increased FEV(1) and FVC. It seems that the effect is not mediated via avoidance of early infections or atopy but rather through a direct effect on lung growth. PMID- 22312016 TI - Prevalence of nontuberculous mycobacterial lung disease in U.S. Medicare beneficiaries. AB - RATIONALE: Pulmonary nontuberculous mycobacteria (PNTM) are an important cause of morbidity among older adults in the United States, but national prevalence estimates are lacking. OBJECTIVES: To describe the prevalence and trends of PNTM disease among adults aged 65 years or older throughout the United States. METHODS: A nationally representative 5% sample of Medicare Part B beneficiaries was analyzed from 1997 to 2007. Demographic and medical claims data were compiled and prevalence estimates for PNTM and selected comorbidities were calculated and trends over time evaluated. Logistic regression was used to identify demographic and geographic factors associated with PNTM. MEASUREMENTS AND MAIN RESULTS: From 1997 to 2007, the annual prevalence significantly increased from 20 to 47 cases/100,000 persons, or 8.2% per year. The period prevalence was 112 cases/100,000 persons, although prevalence was twofold higher among Asians/Pacific Islanders than among whites (228 vs. 116 cases/100,000 persons). Western states had the highest period prevalence at 149 cases/100,000 persons, with Hawaii having the highest prevalence at 396 cases/100,000 persons, followed by southeastern states, which had a period prevalence of 131 cases/100,000 persons. PNTM cases had more comorbid conditions than noncases and were 40% more likely to die than noncases. Women were 1.4 times more likely to be a PNTM case than men. Relative to whites, Asians/Pacific Islanders were twice as likely to be a case, whereas blacks were half as likely. CONCLUSIONS: The prevalence of PNTM is increasing across all regions of the United States and among both men and women. Significant racial/ethnic and geographic differences suggest important gene-environment interactions. PMID- 22312017 TI - Future directions in early cystic fibrosis lung disease research: an NHLBI workshop report. AB - Since the 1989 discovery that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), there has been substantial progress toward understanding the molecular basis for CF lung disease, leading to the discovery and development of new therapeutic approaches. However, the earliest impact of the loss of CFTR function on airway physiology and structure and its relationship to initial infection and inflammation are poorly understood. Universal newborn screening for CF in the United States represents an unprecedented opportunity for investigating CF clinical manifestations very early in life. Recently developed animal models with pulmonary phenotypic manifestations also provide a window into the early consequences of this genetic disorder. For these reasons, the National Heart, Lung, and Blood Institute (NHLBI) convened a working group of extramural experts, entitled "Future Research Directions in Early CF Lung Disease" on September 21 22, 2010, to identify future research directions of great promise in CF. The priority areas identified included (1) exploring pathogenic mechanisms of early CF lung disease; (2) leveraging newborn screening to elucidate the natural history of early lung disease; (3) developing a spectrum of biomarkers of early lung disease that reflects CF pathophysiology, clinical outcome, and response to treatment; (4) exploring the role of genetics/genomics (e.g., modifier genes, gene-environmental interactions, and epigenetics) in early CF pathogenesis; (5) defining early microbiological events in CF lung disease; and (6) elucidating the initial airway inflammatory, remodeling, and repair mechanisms in CF lung disease. PMID- 22312018 TI - Pulmonary administration of a water-soluble curcumin complex reduces severity of acute lung injury. AB - Local or systemic inflammation can result in acute lung injury (ALI), and is associated with capillary leakage, reduced lung compliance, and hypoxemia. Curcumin, a plant-derived polyphenolic compound, exhibits potent anti inflammatory properties, but its poor solubility and limited oral bioavailability reduce its therapeutic potential. A novel curcumin formulation (CDC) was developed by complexing the compound with hydroxypropyl-gamma-cyclodextrin (CD). This results in greatly enhanced water solubility and stability that facilitate direct pulmonary delivery. In vitro studies demonstrated that CDC increased curcumin's association with and transport across Calu-3 human airway epithelial cell monolayers, compared with uncomplexed curcumin solubilized using DMSO or ethanol. Importantly, Calu-3 cell monolayer integrity was preserved after CDC exposure, whereas it was disrupted by equivalent uncomplexed curcumin solutions. We then tested whether direct delivery of CDC to the lung would reduce severity of ALI in a murine model. Fluorescence microscopic examination revealed an association of curcumin with cells throughout the lung. The administration of CDC after LPS attenuated multiple markers of inflammation and injury, including pulmonary edema and neutrophils in bronchoalveolar lavage fluid and lung tissue. CDC also reduced oxidant stress in the lungs and activation of the proinflammatory transcription factor NF-kappaB. These results demonstrate the efficacy of CDC in a murine model of lung inflammation and injury, and support the feasibility of developing a lung-targeted, curcumin-based therapy for the treatment of patients with ALI. PMID- 22312019 TI - Hypoxia response in asthma: differential modulation on inflammation and epithelial injury. AB - Oxygen-sensing prolyl-hydroxylase (PHD)-2 negatively regulates hypoxia-inducible factor (HIF)1-alpha and suppresses the hypoxic response. Hypoxia signaling is thought to be proinflammatory but also attenuates cellular injury and apoptosis. Although increased hypoxic response has been noted in asthma, its functional relevance is unknown. The objectives of this study were to dissect the mechanisms and role of the hypoxic response in asthma pathophysiology. Experimental studies were conducted in mice using acute and chronic allergic models of asthma. The hypoxic response in allergically inflamed lungs was modulated by using pharmacologic PHD inhibitors (ethyl-3-4-dihydroxybenzoic acid [DHB], 1-10 mg/kg) or siRNA-mediated genetic knockdowns. Increased hypoxia response led to exacerbation of the asthma phenotype, with HIF-1alpha knockdown being beneficial. Chronically inflamed lungs from mice treated with 10 mg/kg DHB showed diffuse up regulation of the hypoxia response, severe airway remodeling, and inflammation. Fatal asphyxiation during methacholine challenge was noted. However, bronchial epithelium restricted up-regulation of the hypoxia response seen with low-dose DHB (1 mg/kg) reduced epithelial injury and attenuated the asthmatic phenotype. Up-regulation of the hypoxia response was associated with increased expression of CX3CR1, a lymphocyte survival factor, and increased inflammatory cell infiltrate. This study shows that an exaggerated hypoxia response may contribute to airway inflammation, remodeling, and the development of asthma. However, the hypoxia response may also be protective of epithelial apoptosis at lower levels, and the net effects of modulating the hypoxia response may vary based on the context. PMID- 22312020 TI - Virus-infected alveolar epithelial cells direct neutrophil chemotaxis and inhibit their apoptosis. AB - The alveolar epithelium is a critical target for pulmonary viruses and can produce proinflammatory cytokines and chemokines upon viral infection. However, the molecular interactions between virus-infected alveolar epithelial cells and inflammatory cells, including polymorphonuclear leukocytes (PMNs), have not been thoroughly characterized. Rat coronavirus (RCoV) is used as a model to study the immune response to viral infection in the lung of the natural host. We have developed an in vitro model to characterize the response of PMNs to RCoV-infected type I-like alveolar epithelial (AT1) cells, the primary target for RCoV infection in the alveoli. Multiple CXC chemokines that signal through CXCR2 were required for PMN chemotaxis toward medium from RCoV-infected AT1-like cells (RCoV AT1). Furthermore, RCoV-AT1 inhibited spontaneous PMN apoptosis, including activation of effector caspase 3 and initiator caspases 8 and 9. Use of a selective inhibitor of CXCR2, SB265610, demonstrated that CXCR2 signaling was required for RCoV-AT1-mediated inhibition of PMN apoptosis. These data suggest that CXC chemokines produced by RCoV-infected AT1-like cells inhibit PMN apoptosis during infection. These studies provide new insight into the molecular mechanisms whereby alveolar epithelial cells direct the functions of PMNs during viral infection of the lung. PMID- 22312021 TI - Connectivity map analysis of nonsense-mediated decay-positive BMPR2-related hereditary pulmonary arterial hypertension provides insights into disease penetrance. AB - The molecular mechanisms underlying the reduced penetrance seen in the nonsense mediated decay-positive (NMD+) BMPR2 mutation-associated hereditary pulmonary arterial hypertension (HPAH) remain unknown. We reasoned that the cellular and genetic mechanisms behind this phenomenon could be uncovered by combining expression profiling with Connectivity Map (cMap) analysis. Cultured lymphocytes from 10 patients with HPAH and 10 matched familial control subjects, all with NMD+ BMPR2 mutations, were subjected to expression analysis. For each group, the expression data were combined before analysis. This generated a signature of 23 up-regulated and 12 down-regulated genes in patients with HPAH compared with control subjects (the "PAH penetrance signature"). Although gene set enrichment analysis of this signature was not uniquely informative, cMap analysis identified drugs with expression signatures similar to the PAH penetrance signature. Several of these drugs were predicted to influence reactive oxygen species (ROS) formation. This hypothesis was tested and confirmed in the same cells initially subjected to the expression analysis using quantitative biochemical detection of ROS concentration. We conclude that expression of the PAH penetrance signature represents an increased risk of developing clinical HPAH and that ROS formation may play a role in pathogenesis of HPAH. These results provide the first molecular insights into NMD+ BMPR2 related HPAH penetrance and highlight the potential utility of cMap analyses in pulmonary research. PMID- 22312024 TI - Smoking v. nicotine. PMID- 22312025 TI - Care for smokers. PMID- 22312026 TI - Sudden cardiac arrest. PMID- 22312027 TI - Home-based care. PMID- 22312028 TI - Form and function. PMID- 22312029 TI - Interrelationships between education, occupational social class, and income as determinants of disability retirement. AB - AIMS: The association between a low socioeconomic position and disability retirement is established in the literature, but the interrelationships between various subdomains of socioeconomic position are poorly understood. We examined the independent and interdependent effects of education, social class, and income on disability retirement. METHODS: Using nationally representative register data we followed up over 260,000 Finns aged 30-63 at the end of 1995 for disability retirement from 1996 to 2004. Cox regression analysis was used to calculate hazard ratios (HR) and relative indices of inequality (RII). RESULTS: Each socioeconomic indicator had a linear negative association with disability retirement. The socioeconomic gradients were stronger in the younger age groups. The effect of education was largely mediated through succeeding social class. Social class was largely explained by preceding education, but was only moderately mediated through income. Income was largely explained by education, and even further by social class. The independent effects of education, social class, and income on disability retirement as measured by the RII were 1.74 (95% CI 1.60-1.90), 1.95 (1.78-2.15), and 1.35 (1.25-1.47) for men and 1.76 (1.61 1.92), 2.14 (1.95-2.34), and 1.14 (1.05-1.24) for women. CONCLUSIONS: The effects of socioeconomic position on disability retirement may not be fully captured if the pathways between the various subdomains are disregarded. Our results suggest that efforts to delay and prevent disability retirement should focus on lifestyle and cognitive factors associated with education, as well as on factors associated with social class such as working conditions and power resources. PMID- 22312030 TI - Public health burden due to infections by verocytotoxin-producing Escherichia coli (VTEC) and Campylobacter spp. as estimated by cost of illness and different approaches to model disability-adjusted life years. AB - AIMS: To estimate disability-adjusted life years (DALY) and cost of illness (COI) associated with the gastrointestinal bacterial pathogens Campylobacter and verocytotoxin-producing Escherichia coli (VTEC) in Sweden and to investigate the impact of variability in health outcomes, data availability, and different assumptions about underreporting on DALY. METHODS: Data from the Swedish notification system, public databases, and the literature were used to estimate COI and DALY. DALY was modelled using a deterministic and a stochastic approach, the latter describing variation in health outcomes between individuals. Effects of different assumptions about underreporting of gastroenteritis were evaluated in separate scenarios. RESULTS: COI and DALY were greater for Campylobacter than for VTEC. Years of life lost due to haemolytic uraemic syndrome and years lived with gastroenteritis constituted most of DALY for VTEC and Campylobacter, respectively. Productivity losses due to gastroenteritis constituted the main cost associated with both pathogens. Degree of underreporting had a greater impact on DALY for Campylobacter, due to higher estimated incidence of gastroenteritis associated with campylobacteriosis. CONCLUSIONS: Pathogen specific health outcomes and data quality may influence the preferred modelling approach. There was a fair agreement between modelling approaches, but the stochastic model reflected the contribution of some rare health outcomes not captured in the deterministic model. Health outcomes excluded due to lack of data lead to an underestimation of the total burden associated with the pathogens. Increased knowledge, especially on the degree of underreporting and the contribution of the pathogens to sequelae, is needed to further improve public health burden estimates for these pathogens in Sweden. PMID- 22312031 TI - Could the social environment trigger the induction of diabetes related autoantibodies in young children? AB - AIMS: The onset and progression of the autoimmune process leading to type 1 diabetes is partly dependent on genetic predisposition and partly on environmental factors. We have implemented a study design where 1-year-old children, from two equally sized, neighbouring but socioeconomically different cities, were compared for the induction of beta-cell autoantibodies. METHODS: This study comprises 2448 newborn infants, all living in the urban parts of the twin cities, followed prospectively with regular biological samples and questionnaires in a major population-based study. Of these, a random sample of 1497 children were tested for tyrosine phosphatase (IA-2A) and 1409 children for glutamic acid decarboxylase (GADA). Other documented risk factors of beta-cell autoimmunity and type 1 diabetes, such as family characteristics, dietary factors, and psychosocial factors were also included in the analysis. RESULTS: The risk for diabetes-related autoantibodies, both against GADA and IA-2A (>95% cut off), was significantly higher (p<0.0001) among children from the blue-collar than from the white-collar city. This difference persisted still after adjustment for other previously documented risk factors. Some of these previously known risk factors remained significant in the multivariate analysis as independent explanatory factors, in addition to living in a blue-collar city. CONCLUSIONS: Factors in the social environment could trigger the induction of diabetes-related autoantibodies in 1-year-old children. These results point out that our present knowledge of factors influencing the autoimmune process might be widen to also include factors in the social environment of the community. PMID- 22312032 TI - A cluster randomised controlled trial of an adolescent smoking cessation intervention: short and long-term effects. AB - BACKGROUND: There is a lack of effective smoking cessation interventions which have a high reach among adolescent smokers. METHOD: We conducted a randomised controlled trial of an adolescent smoking cessation intervention for students aged 15-21 at 22 continuation schools in Denmark. The intervention was a minimal intervention based on events with short counselling and a range of self-help materials. Our 1-month follow up consisted of 514 baseline daily smokers and the 14-month follow up of 369 daily smokers. RESULTS: We found positive short-term effects regarding smoking cessation (adjusted OR 4.50, 95% CI 1.20-16.86), self efficacy (p=0.01), and intentions to quit (p=0.004). However, none of these effects were maintained at 1-year follow up. The intervention was successful in reaching more than half of all daily smokers in the target group with more than 30% receiving counselling at least once in the intervention period. CONCLUSIONS: This trial shows that a "minimal" intervention can produce short-term effects but that this approach is insufficient in producing long-term effects. PMID- 22312033 TI - Beneficial effect of astaxanthin on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced liver injury in rats. AB - Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) represents a potential health risk and hepatotoxicity. Astaxanthin (ASTA) exhibits antioxidant properties and can influence hepatotoxicity. Therefore, the present study was carried out for using ASTA against hepatotoxicity induced by TCDD in the liver of rats. Animals were treated intraperitoneally daily with TCDD (8 ug/kg body weight (b.w.)), ASTA (12.5 mg/kg b.w. and 25 mg/kg b.w.) and TCDD plus ASTA (12.5 and 25 mg/kg b.w.) for 21 days. TCDD significantly decreased the activities of antioxidant enzymes and resulted in serious pathological findings. Moreover, the rate of micronucleus (MN) in hepatocytes increased after treating with TCDD. The activities of enzymes, frequencies of MNs and liver histology in lower dosage group of ASTA remained unchanged compared with the control group. In rats treated with ASTA, at higher dosage alone, the MNs remained unchanged and the activities of antioxidant enzymes significantly increased. The presence of ASTA (except for lower dose) with TCDD alleviated its pathological effects in hepatic tissue. ASTA also prevented the suppression of antioxidant enzymes in the livers of animals exposed to TCDD and displayed a strong protective effect against MNs. Thus, the present findings might provide new insight into the development of therapeutic and preventive approaches of TCDD toxicity. PMID- 22312034 TI - Determination of chemical composition and genotoxic effects of essential oil obtained from Nepeta nuda on Zea mays seedlings. AB - We aimed to determine the genotoxic potential of essential oil (EO) obtained from Nepeta nuda. The chemical content of EO was measured via gas chromatography/mass spectrometry. The most abundant contents were 4aalpha,7beta,7aalpha-nepetalactone (18.10%), germacrene (15.68%) and elemol (14.38%). For genotoxic effects of EO, Zea mays' seeds were exposed to four different concentrations of this oil. Inhibition of root and stem growth were observed with an increase in EO concentrations. Randomly amplified polymorphic DNA (RAPD) method was used to determine the genotoxic effects of EO. Some changes occurred in RAPD profiles of germinated EO-treated seeds. Even though total soluble protein quantity vary, the data observed from the protein profiles of sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that there was a little differentiation between band profiles of treated samples and control group. We concluded that the basis of interactions between plants, like allelopathy, may be related with genotoxic effects of EO. PMID- 22312035 TI - Determination of aflatoxin M1 in milk by high-performance liquid chromatography in Mashhad (north east of Iran). AB - The aim of this study was to evaluate aflatoxin M1 (AFM1) contamination in milk samples in Mashhad in Iran. A total of 60 milk samples were collected from retail stores of five regions in June 2011. The occurrence and concentration range of AFM1 in the samples were investigated by high-performance liquid chromatography method. AFM1 was found in 100% of the examined milk samples by average concentration of 16.16 ng/L and the contamination level ranging between 2 and 64 ng/L. The concentration of AFM1 in all the samples was lower than the Iranian national standard and Food and Drug Administration limit (500 ng/L), and only in one (1.6%) of the samples, the concentration of AFM1 was greater than the maximum tolerance limit (50 ng/L) accepted by European Union and Codex Alimentarius Commission. Statistical evaluation showed no significant difference between the mean concentrations of AFM1 in milk samples taken from different regions (p > 0.05). PMID- 22312036 TI - Cortisol secretion, bone health, and bone loss: a cross-sectional and prospective study in normal non-osteoporotic women in the early postmenopausal period. AB - OBJECTIVE: The aim of the study was to evaluate the relationship between cortisol secretion, bone health, and bone loss in a cohort of normal women in the early postmenopausal period. METHODS: We measured lumbar and hip bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) and heel ultrasound parameters in 82 healthy, nonosteoporotic (lumbar T-score >=-2.0) women (median age 52.5 years, range 42-61). These women were examined in two sessions, 1 year apart, in the early postmenopausal period (onset of menopause between 6 and 60 months). Parameters of the hypothalamic-pituitary-adrenal (HPA) axis function were morning serum cortisol, morning and midnight salivary cortisol, 24-h urinary free cortisol (UFC), serum cortisol after 0.5 and 1 mg overnight dexamethasone, and DHEA-S. RESULTS: In multiple regression analyses, the following significant inverse correlations were found: i) lumbar BMD and either 24-h UFC (P<0.005) or morning serum cortisol (P<0.05), ii) total femur and femoral neck BMD with morning serum cortisol (P=0.05 and P<0.05), and iii) heel ultrasound stiffness index and midnight salivary cortisol (P<0.005). The annual rate of change in lumbar and femoral BMD did not correlate with any of the above-mentioned hormonal variables. No difference was found in the parameters of HPA axis function in slow (loss of BMD <1%) vs fast (loss of BMD >=3%) bone losers. CONCLUSIONS: HPA axis may contribute to postmenopausal bone health, but differences in cortisol secretion do not influence the differential rate of bone loss between slow and fast bone losers in the early postmenopausal period, at least in healthy women. PMID- 22312037 TI - Epicardial adipose tissue volume as a predictor for coronary artery disease in diabetic, impaired fasting glucose, and non-diabetic patients presenting with chest pain. AB - AIMS: Epicardial adipose tissue (EAT) volume has been associated with coronary artery disease (CAD). As diabetes mellitus type 2 (DM2) patients have higher EAT volumes, it has been suggested that EAT may play a role in promoting CAD in these patients. The aim of this study was to examine the association between EAT and CAD in DM2, impaired fasting glucose (IFG) and control patients presenting with stable chest pain. METHODS AND RESULTS: A total of 410 stable chest pain patients underwent multidetector cardiac computed tomography angiography (CCTA) to assess the presence of CAD. The extent of CAD was expressed as the number of affected segments. The EAT volume was measured using three-dimensional volumetric quantification. The EAT was compared using ANOVA, logistic and linear regression models were used to assess its predictive value. Multivariable regression analysis corrected for traditional risk factors was performed. Eighty-three patients had DM2, 118 IFG and there were 209 controls. DM2 as well as IFG patients had higher EAT volumes compared with controls (98 +/- 41, 92 +/- 39, and 75 +/- 34 cm(3), respectively; P < 0.001). EAT predicted the presence (OR: 1.01; P < 0.001) and the extent of CAD (B: 0.01; P < 0.001). The associations were equal in all subgroups. However, in a multivariable regression model corrected for traditional cardiovascular risk factors, EAT was not an independent predictor for the presence or extent of CAD (OR: 1.00; P = 0.88 and B: -0.11; P = 0.68, respectively). CONCLUSION: The EAT volume is associated with CAD in DM2, IFG, and control patients. However, EAT is not an independent predictor for CAD in patients presenting with stable chest pain. PMID- 22312038 TI - A randomized double-blind crossover trial of triventricular versus biventricular pacing in heart failure. AB - AIMS: A significant proportion of patients implanted with biventricular (BiV) devices fail to respond. Clinical response may be improved by additional ventricular stimulation sites. This single-centre, double-blinded randomized crossover trial aimed to determine whether long-term multisite ventricular pacing is superior to conventional BiV pacing in heart failure patients. METHODS AND RESULTS: A total of 43 patients referred for cardiac resynchronization therapy (CRT) underwent transvenous implantation of a triventricular (TriV) device. Pacing leads were positioned in the right ventricular (RV) apex and a lateral coronary sinus (CS) branch, with a third ventricular lead implanted in a further lateral CS branch in 23 patients (group A) and on the high RV septum in 20 patients (group B). Devices were programmed in a randomized order to four pre determined pacing configurations: conventional BiV, TriV, and dual-site and single-site left bentricular (LV) or RV pacing for 3-month periods with clinical and echo assessment at the end of each period. The primary endpoint was the comparison of 6 min walk distance (6MW) after 3 months of BiV vs. TriV pacing; secondary endpoints were Minnesota Living With Heart Failure (MLWHF) scores, and LV dimensions and function. The 12-month follow-up period was completed by 37 patients. Compared with BiV pacing, TriV pacing resulted in significant improvements in 6MW (451 +/- 112 m vs. 425 +/- 119 m, P = 0.008), MLWHF (32 +/- 19 vs. 38 +/- 24, P = 0.036), LV end-systolic volume (158 +/- 79mL vs. 168 +/- 76 mL, P < 0.05), and ejection fraction (30 +/- 8% vs. 27 +/- 8%, P < 0.05). CONCLUSIONS: TriV pacing was associated with significant improvements in clinical and echocardiographic parameters compared with BiV pacing. PMID- 22312039 TI - Honor killings in the Middle East and North Africa: a systematic review of the literature. AB - A systematic review of the research literature on honor killings in the Middle East and North Africa (MENA) indicates a paucity of studies relative to the presumed magnitude of the problem. Forty articles were reviewed and critically appraised, of which only 9 contained primary data and 11 presented original secondary analyses. Despite a recent increase in published studies, persistent methodological limitations restrict the generalizability of findings. Most studies focus on legal aspects, determinants, and characteristics of victims and perpetrators. Victims are mostly young females murdered by their male kin. Unambiguous evidence of a decline in tolerance of honor killings remains elusive. PMID- 22312040 TI - Husband's control and sexual coercion within marriage: findings from a population based survey in Egypt. AB - This article examined sexual coercion within marriage in Egypt. Using cross sectional survey data from a representative sample of married Egyptian women (N = 5,240), associations between forced intercourse and husband's control, as well as other relevant sociodemographic factors, were assessed through binary logistic regression models. The lifetime prevalence of forced intercourse was 6.2% and 4.6% during the past year, and husband's control was significantly associated with forced intercourse during a woman's lifetime (odds ratio = 3.5) and past year (odds ratio = 2.8). Interventions addressing gender patriarchy and men's control may decrease incidence of sexual coercion in Egypt and similar contexts. PMID- 22312043 TI - Diverse approaches to analysing the history of human and pathogen evolution: how to tell the story of the past 70 000 years. AB - The meeting 'Human evolution, migration and history revealed by genetics, immunity and infection', along with the follow-on satellite meeting at the Kavli Centre over the subsequent two days, brought together diverse talents. The aim was to see if new insights could be gained by bringing together those who have interests in the past 50-100 000 years of human history, overlaying the perspectives of palaeogeneticists, anthropologists, human geneticists, pathogen geneticists, immunologists, disease modellers, linguists, immunogeneticists, historians and archaeologists. It rapidly became clear that while all may agree on the broad brush-strokes including 'out-of-Africa' and the general approximations of timelines, diverse approaches may often suggest somewhat different ways of telling the story. PMID- 22312044 TI - Out-of-Africa, the peopling of continents and islands: tracing uniparental gene trees across the map. AB - Genetic relationships between human groups were first studied by comparisons of relative allele frequency at multiple loci. Geographical study of detailed, highly resolved trees of single, non-recombining uniparental loci (mitochondrial DNA: mtDNA and Y chromosome/non-recombining Y: NRY), following specific lineages rather than populations, then revolutionized knowledge of the peopling of the world, although, curiously, the use of geographically highly specific mutations that protect against malaria, found on individual autosomal globin genes, were first in single-locus phylogeography. mtDNA, with its high single nucleotide polymorphism (SNP) mutation rates and relative ease of dating, led the way and gave stronger proof of the recent near replacement of all human species by anatomically modern humans (AMH). AMH left Africa via a single southern exit about 70 000 years ago and rapidly spread around the Indian Ocean towards the Antipodes, long before a small branch left a South Asian colony, earlier on the trail, to populate Europe. The worldwide skeleton phylogeny of mtDNA is fully resolved, but a regional analysis will continue to illuminate subsequent migrations. NRY with a lower SNP mutation rate still has a dating problem relating to use the of single tandem repeats (STRs), but has validated mtDNA results and with more geographical specificity and genomic size, as with the autosomal human genome, has much more detail to offer for the future. PMID- 22312045 TI - Human skin pigmentation, migration and disease susceptibility. AB - Human skin pigmentation evolved as a compromise between the conflicting physiological demands of protection against the deleterious effects of ultraviolet radiation (UVR) and photosynthesis of UVB-dependent vitamin D(3). Living under high UVR near the equator, ancestral Homo sapiens had skin rich in protective eumelanin. Dispersals outside of the tropics were associated with positive selection for depigmentation to maximize cutaneous biosynthesis of pre vitamin D(3) under low and highly seasonal UVB conditions. In recent centuries, migrations and high-speed transportation have brought many people into UVR regimes different from those experienced by their ancestors and, accordingly, exposed them to new disease risks. These have been increased by urbanization and changes in diet and lifestyle. Three examples-nutritional rickets, multiple sclerosis (MS) and cutaneous malignant melanoma (CMM)-are chosen to illustrate the serious health effects of mismatches between skin pigmentation and UVR. The aetiology of MS in particular provides insight into complex and contingent interactions of genetic and environmental factors necessary to trigger lethal disease states. Low UVB levels and vitamin D deficiencies produced by changes in location and lifestyle pose some of the most serious disease risks of the twenty first century. PMID- 22312046 TI - The impact of recent events on human genetic diversity. AB - The historical record tells us stories of migrations, population expansions and colonization events in the last few thousand years, but what was their demographic impact? Genetics can throw light on this issue, and has mostly done so through the maternally inherited mitochondrial DNA (mtDNA) and the male specific Y chromosome. However, there are a number of problems, including marker ascertainment bias, possible influences of natural selection, and the obscuring layers of the palimpsest of historical and prehistorical events. Y-chromosomal lineages are particularly affected by genetic drift, which can be accentuated by recent social selection. A diversity of approaches to expansions in Europe is yielding insights into the histories of Phoenicians, Roma, Anglo-Saxons and Vikings, and new methods for producing and analysing genome-wide data hold much promise. The field would benefit from more consensus on appropriate methods, and better communication between geneticists and experts in other disciplines, such as history, archaeology and linguistics. PMID- 22312047 TI - Human-specific evolution of killer cell immunoglobulin-like receptor recognition of major histocompatibility complex class I molecules. AB - In placental mammals, natural killer (NK) cells are a population of lymphocytes that make unique contributions to immune defence and reproduction, functions essential for survival of individuals, populations and species. Modulating these functions are conserved and variable NK-cell receptors that recognize epitopes of major histocompatibility complex (MHC) class I molecules. In humans, for example, recognition of human leucocyte antigen (HLA)-E by the CD94:NKG2A receptor is conserved, whereas recognition of HLA-A, B and C by the killer cell immunoglobulin-like receptors (KIRs) is diversified. Competing demands of the immune and reproductive systems, and of T-cell and NK-cell immunity-combined with the segregation on different chromosomes of variable NK-cell receptors and their MHC class I ligands-drive an unusually rapid evolution that has resulted in unprecedented levels of species specificity, as first appreciated from comparison of mice and humans. Counterparts to human KIR are present only in simian primates. Observed in these species is the coevolution of KIR and the four MHC class I epitopes to which human KIR recognition is restricted. Unique to hominids is the emergence of the MHC-C locus as a supplier of specialized and superior ligands for KIR. This evolutionary trend is most highly elaborated in the chimpanzee. Unique to the human KIR locus are two groups of KIR haplotypes that are present in all human populations and subject to balancing selection. Group A KIR haplotypes resemble chimpanzee KIR haplotypes and are enriched for genes encoding KIR that bind HLA class I, whereas group B KIR haplotypes are enriched for genes encoding receptors with diminished capacity to bind HLA class I. Correlating with their balance in human populations, B haplotypes favour reproductive success, whereas A haplotypes favour successful immune defence. Evolution of the B KIR haplotypes is thus unique to the human species. PMID- 22312048 TI - The Polynesian gene pool: an early contribution by Amerindians to Easter Island. AB - It is now generally accepted that Polynesia was first settled by peoples from southeast Asia. An alternative that eastern parts of Polynesia were first inhabited by Amerindians has found little support. There are, however, many indications of a 'prehistoric' (i.e. before Polynesia was discovered by Europeans) contact between Polynesia and the Americas, but genetic evidence of a prehistoric Amerindian contribution to the Polynesian gene pool has been lacking. We recently carried out genomic HLA (human leucocyte antigen) typing as well as typing for mitochondrial DNA (mtDNA) and Y chromosome markers of blood samples collected in 1971 and 2008 from reputedly non-admixed Easter Islanders. All individuals carried HLA alleles and mtDNA types previously found in Polynesia, and most of the males carried Y chromosome markers of Polynesian origin (a few had European Y chromosome markers), further supporting an initial Polynesian population on Easter Island. The HLA investigations revealed, however, that some individuals also carried HLA alleles which have previously almost only been found in Amerindians. We could trace the introduction of these Amerindian alleles to before the Peruvian slave trades, i.e. before the 1860s, and provide suggestive evidence that they were introduced already in prehistoric time. Our results demonstrate an early Amerindian contribution to the Polynesian gene pool on Easter Island, and illustrate the usefulness of typing for immunogenetic markers such as HLA to complement mtDNA and Y chromosome analyses in anthropological investigations. PMID- 22312049 TI - Tracking human migrations by the analysis of the distribution of HLA alleles, lineages and haplotypes in closed and open populations. AB - The human leucocyte antigen (HLA) system shows extensive variation in the number and function of loci and the number of alleles present at any one locus. Allele distribution has been analysed in many populations through the course of several decades, and the implementation of molecular typing has significantly increased the level of diversity revealing that many serotypes have multiple functional variants. While the degree of diversity in many populations is equivalent and may result from functional polymorphism(s) in peptide presentation, homogeneous and heterogeneous populations present contrasting numbers of alleles and lineages at the loci with high-density expression products. In spite of these differences, the homozygosity levels are comparable in almost all of them. The balanced distribution of HLA alleles is consistent with overdominant selection. The genetic distances between outbred populations correlate with their geographical locations; the formal genetic distance measurements are larger than expected between inbred populations in the same region. The latter present many unique alleles grouped in a few lineages consistent with limited founder polymorphism in which any novel allele may have been positively selected to enlarge the communal peptide-binding repertoire of a given population. On the other hand, it has been observed that some alleles are found in multiple populations with distinctive haplotypic associations suggesting that convergent evolution events may have taken place as well. It appears that the HLA system has been under strong selection, probably owing to its fundamental role in varying immune responses. Therefore, allelic diversity in HLA should be analysed in conjunction with other genetic markers to accurately track the migrations of modern humans. PMID- 22312050 TI - Distinct evolutionary strategies of human leucocyte antigen loci in pathogen-rich environments. AB - Human leucocyte antigen (HLA) loci have a complex evolution where both stochastic (e.g. genetic drift) and deterministic (natural selection) forces are involved. Owing to their extraordinary level of polymorphism, HLA genes are useful markers for reconstructing human settlement history. However, HLA variation often deviates significantly from neutral expectations towards an excess of genetic diversity. Because HLA molecules play a crucial role in immunity, this observation is generally explained by pathogen-driven-balancing selection (PDBS). In this study, we investigate the PDBS model by analysing HLA allelic diversity on a large database of 535 populations in relation to pathogen richness. Our results confirm that geographical distances are excellent predictors of HLA genetic differentiation worldwide. We also find a significant positive correlation between genetic diversity and pathogen richness at two HLA class I loci (HLA-A and -B), as predicted by PDBS, and a significant negative correlation at one HLA class II locus (HLA-DQB1). Although these effects are weak, as shown by a loss of significance when populations submitted to rapid genetic drift are removed from the analysis, the inverse relationship between genetic diversity and pathogen richness at different loci indicates that HLA genes have adopted distinct evolutionary strategies to provide immune protection in pathogen-rich environments. PMID- 22312051 TI - Evolution, revolution and heresy in the genetics of infectious disease susceptibility. AB - Infectious pathogens have long been recognized as potentially powerful agents impacting on the evolution of human genetic diversity. Analysis of large-scale case-control studies provides one of the most direct means of identifying human genetic variants that currently impact on susceptibility to particular infectious diseases. For over 50 years candidate gene studies have been used to identify loci for many major causes of human infectious mortality, including malaria, tuberculosis, human immunodeficiency virus/acquired immunodeficiency syndrome, bacterial pneumonia and hepatitis. But with the advent of genome-wide approaches, many new loci have been identified in diverse populations. Genome-wide linkage studies identified a few loci, but genome-wide association studies are proving more successful, and both exome and whole-genome sequencing now offer a revolutionary increase in power. Opinions differ on the extent to which the genetic component to common disease susceptibility is encoded by multiple high frequency or rare variants, and the heretical view that most infectious diseases might even be monogenic has been advocated recently. Review of findings to date suggests that the genetic architecture of infectious disease susceptibility may be importantly different from that of non-infectious diseases, and it is suggested that natural selection may be the driving force underlying this difference. PMID- 22312052 TI - Host-pathogen coevolution in human tuberculosis. AB - Tuberculosis (TB) is a disease of antiquity. Yet TB today still causes more adult deaths than any other single infectious disease. Recent studies show that contrary to the common view postulating an animal origin for TB, Mycobacterium tuberculosis complex (MTBC), the causative agent of TB, emerged as a human pathogen in Africa and colonized the world accompanying the Out-of-Africa migrations of modern humans. More recently, evolutionarily 'modern' lineages of MTBC expanded as a consequence of the global human population increase, and spread throughout the world following waves of exploration, trade and conquest. While epidemiological data suggest that the different phylogenetic lineages of MTBC might have adapted to different human populations, overall, the phylogenetically 'modern' MTBC lineages are more successful in terms of their geographical spread compared with the 'ancient' lineages. Interestingly, the global success of 'modern' MTBC correlates with a hypo-inflammatory phenotype in macrophages, possibly reflecting higher virulence, and a shorter latency in humans. Finally, various human genetic variants have been associated with different MTBC lineages, suggesting an interaction between human genetic diversity and MTBC variation. In summary, the biology and the epidemiology of human TB have been shaped by the long-standing association between MTBC and its human host. PMID- 22312053 TI - Insights from genomic comparisons of genetically monomorphic bacterial pathogens. AB - Some of the most deadly bacterial diseases, including leprosy, anthrax and plague, are caused by bacterial lineages with extremely low levels of genetic diversity, the so-called 'genetically monomorphic bacteria'. It has only become possible to analyse the population genetics of such bacteria since the recent advent of high-throughput comparative genomics. The genomes of genetically monomorphic lineages contain very few polymorphic sites, which often reflect unambiguous clonal genealogies. Some genetically monomorphic lineages have evolved in the last decades, e.g. antibiotic-resistant Staphylococcus aureus, whereas others have evolved over several millennia, e.g. the cause of plague, Yersinia pestis. Based on recent results, it is now possible to reconstruct the sources and the history of pandemic waves of plague by a combined analysis of phylogeographic signals in Y. pestis plus polymorphisms found in ancient DNA. Different from historical accounts based exclusively on human disease, Y. pestis evolved in China, or the vicinity, and has spread globally on multiple occasions. These routes of transmission can be reconstructed from the genealogy, most precisely for the most recent pandemic that was spread from Hong Kong in multiple independent waves in 1894. PMID- 22312054 TI - Genome-wide scans provide evidence for positive selection of genes implicated in Lassa fever. AB - Rapidly evolving viruses and other pathogens can have an immense impact on human evolution as natural selection acts to increase the prevalence of genetic variants providing resistance to disease. With the emergence of large datasets of human genetic variation, we can search for signatures of natural selection in the human genome driven by such disease-causing microorganisms. Based on this approach, we have previously hypothesized that Lassa virus (LASV) may have been a driver of natural selection in West African populations where Lassa haemorrhagic fever is endemic. In this study, we provide further evidence for this notion. By applying tests for selection to genome-wide data from the International Haplotype Map Consortium and the 1000 Genomes Consortium, we demonstrate evidence for positive selection in LARGE and interleukin 21 (IL21), two genes implicated in LASV infectivity and immunity. We further localized the signals of selection, using the recently developed composite of multiple signals method, to introns and putative regulatory regions of those genes. Our results suggest that natural selection may have targeted variants giving rise to alternative splicing or differential gene expression of LARGE and IL21. Overall, our study supports the hypothesis that selective pressures imposed by LASV may have led to the emergence of particular alleles conferring resistance to Lassa fever, and opens up new avenues of research pursuit. PMID- 22312055 TI - Human population structure and the adaptive response to pathogen-induced selection pressures. AB - The past few years of research in human evolutionary genetics have provided novel insights and questions regarding how human adaptations to recent selective pressures have taken place. Here, we review the advances most relevant to understanding human evolution in response to pathogen-induced selective pressures. Key insights come from theoretical models of adaptive evolution, particularly those that consider spatially structured populations, and from empirical population genomic studies of adaptive evolution in humans. We also review the CCR5-Delta32 HIV resistance allele as a case study of pathogen resistance in humans. Taken together, the results make clear that the human response to pathogen-induced selection pressures depends on a complex interplay between the age of the pathogen, the genetic basis of potential resistance phenotypes, and how population structure impacts the adaptive process in humans. PMID- 22312056 TI - Host genetics and population structure effects on parasitic disease. AB - Host genetic factors exert significant influences on differential susceptibility to many infectious diseases. In addition, population structure of both host and parasite may influence disease distribution patterns. In this study, we assess the effects of population structure on infectious disease in two populations in which host genetic factors influencing susceptibility to parasitic disease have been extensively studied. The first population is the Jirel population of eastern Nepal that has been the subject of research on the determinants of differential susceptibility to soil-transmitted helminth infections. The second group is a Brazilian population residing in an area endemic for Trypanosoma cruzi infection that has been assessed for genetic influences on differential disease progression in Chagas disease. For measures of Ascaris worm burden, within-population host genetic effects are generally more important than host population structure factors in determining patterns of infectious disease. No significant influences of population structure on measures associated with progression of cardiac disease in individuals who were seropositive for T. cruzi infection were found. PMID- 22312057 TI - Endothelial dysfunction enhances the pulmonary and systemic vasodilator effects of phosphodiesterase-5 inhibition in awake swine at rest and during treadmill exercise. AB - Cardiovascular disease is characterized by impaired exercise capacity and endothelial dysfunction, i.e. reduced bioavailability of nitric oxide (NO). Phosphodiesterase-5 (PDE5) inhibition is a promising vasodilator therapy, but its effects on pulmonary and systemic hemodynamic responses to exercise in the absence, and particularly in the presence, of endothelial dysfunction have not been studied. We investigated the effects of PDE5 inhibitor EMD360527 in chronically instrumented swine at rest and during exercise with and without NO synthase inhibition (N(omega)-nitro-l-arginine; NLA). PDE5 inhibition caused a 19 +/- 3% decrease in systemic vascular resistance (SVR) and a 24 +/- 4% decrease in pulmonary vascular resistance (PVR) at rest. At maximal exercise, PDE5 inhibition caused a 13 +/- 1% decrease in SVR and a 29 +/- 3% decrease in PVR. NLA enhanced PDE5-inhibition-induced pulmonary (decrease in PVR 32 +/- 12% at rest and 41 +/- 3% during exercise) and systemic (decrease in SVR 24 +/- 5% at rest and 18 +/- 3% during exercise) vasodilation. Similarly, NLA increased the pulmonary and systemic vasodilation to nitroprusside and 8-bromo-cyclic guanosine monophosphate (cGMP), indicating that inhibition of NO synthase increases responsiveness to stimulation of the NO/cGMP pathway. Thus, PDE5 inhibition causes pulmonary and systemic vasodilation that is, respectively, maintained and slightly blunted during exercise. The degree of dilation in both the pulmonary and systemic beds were paradoxically enhanced in the presence of reduced bioavailability of NO, suggesting that this vasodilator therapy is most effective in patients with cardiovascular disease. PMID- 22312058 TI - Effects of selenium on the vessel walls and anti-elastin antibodies in spontaneously hypertensive rats. AB - Selenium (Se) is an exogenous antioxidant that performs its role via expression of selenoproteins. Pathological changes of the structure of the vessel wall, elastin turnover and collagen production may lead to increased stiffness of the vessels with decreased blood flow to the peripheries. The level of anti-elastin antibodies (AEABs) may give information for elastin metabolism. The aim of the study is to investigate the influence of Se intake on the vessel wall changes and production of AEABs in spontaneously hypertensive rats (SHR). Twenty-four male, 32-week-old SHR were used, divided into three groups, G1, G2 and G3. Before blood and morphological testing, G1 received a low-Se diet for eight weeks, G2 received a diet with adequate Se content and G3 received a diet with Se supplementation. The Se nutritional status was assessed by determination of glutathione peroxidase 1 (GPx-1) activity in whole blood, using the 'Ransel' kit. The rats from group G3 showed higher GPx-1 activity and lower level of AEABs than the other groups (P = 0.021), and the aortic wall histology showed slight degenerative changes compared with other rats. A low-Se diet caused severe changes to the aortic wall's ultrastructure, whereas Se supplementation slowed the changes down. The morphometry revealed a thicker abdominal aortic wall in rats of G1 compared with the other groups, and reduced thickness of the wall of the left coronary artery in G3 compared with the other groups (P < 0.05). Our results have shown that low Se intake leads to severe changes in the vessel walls in SHR, whereas selenium supplementation slows down the elastin degradation and degenerative changes of the vessel walls. PMID- 22312059 TI - Nanobiology and physiology of growth hormone secretion. AB - Growth hormone (GH) secretion is controlled by hypothalamic releasing hormones from the median eminence together with hormones and neuropeptides produced by peripheral organs. Secretion of GH involves movement of secretory vesicles along microtubules, transient 'docking' with the porosome in the cell membrane and subsequent release of GH. Release of GH is stimulated by GH releasing hormone (GHRH) and inhibited by somatostatin (SRIF). Ghrelin may be functioning to stimulate GH release from somatotropes acting via the GH secretagogue (GHS) receptor (GHSR). However, recent physiological studies militate against this. In addition, ghrelin does influence GH release acting within the hypothalamus. Release of GH from the somatotropes involves the GH-containing secretory granules moving close to the cell surface followed by transitory fusion of the secretory granules with the porosomes located in multiple secretory pits in the cell membrane. Other peptides/proteins can influence GH secretion, particularly in species of non-mammalian vertebrates. PMID- 22312060 TI - Guidelines for the management of varicose veins. AB - Recently published evidence-based guidelines of the Society for Vascular Surgery (SVS) and the American Venous Forum (AVF) include recommendations for evaluation, classification, outcome assessment and therapy of patients with varicose veins and more advanced chronic venous insufficiency (CVI). The need for such guidelines has been evident since imaging techniques and minimally invasive technologies have progressed by leaps and bounds and radiofrequency ablation, laser and sclerotherapy have largely replaced classical open surgery of saphenous stripping. This report reviews the most important guidelines recommended by the SVS/AVF Venous Guideline Committee. It is obvious, however, that some of the technology that is recommended in North America is either not available or not affordable in some parts of the world for patients with varicose veins and CVI. The readers are urged therefore to also consult the guidelines of their national societies, recent publications of the National Institute for Clinical Excellence and the Venous Forum of the Royal Society of Medicine. Venous specialists should also keep in mind that scientific evidence should always be combined with the physician's clinical experience and the patient's preference when the best treatment is selected for an individual patient. PMID- 22312061 TI - Diagnosis and follow-up of varicose veins with duplex ultrasound: how and why? AB - Chronic venous disease (CVD) is very prevalent and causes a significant financial burden in Western societies. Accurate diagnosis is mandatory to define the anatomy and pathophysiology involved in the disease process. Duplex ultrasound (DU) is a well-established non-invasive tool used for varicose veins work-up that, most recently, has also been utilized for follow-up after endovenous procedures such as endovenous laser or radiofrequency ablation and foam sclerotherapy. Insightful information on how DU is performed during varicose veins work-up and the rationale of DU utilization for endovenous procedures are discussed. PMID- 22312062 TI - Treatment options, clinical outcome (quality of life) and cost benefit (quality adjusted life year) in varicose vein treatment. AB - Varicose veins are an extremely common condition causing morbidity; however, with current financial pressures, treatment of such benign diseases is controversial. Many procedures allow the treatment of varicose veins with minimal cost and extensive literature supporting differing approaches. Here we explore the underlying evidence base for treatment options, the effect on clinical outcome and the cost-benefit economics associated with varicose vein treatment. The method of defining clinical outcome with quality-of-life assessment tools is also investigated to explain concepts of treatment success beyond abolition of reflux. PMID- 22312063 TI - The relevance of the natural history of varicose veins and refunded care. AB - Chronic venous disease (CVD) is one of the most common diseases in our population. Aside from venous symptoms like heaviness and pain, which are present in about 50% of the general population, signs of CVD include varicose veins (VVs), oedema, eczema, venous eczema, hyperpigmentation, white atrophy, lipodermatosclerosis and venous ulcers. The aim of this paper is to review current literature for the relevance of natural history of VVs in refunded care. Available papers on VVs, progression of the disease and complications were reviewed. Prevalence of VVs is high with more than 20% in the general population. Information on progression of uncomplicated VV to chronic venous insufficiency (CVI) is rare. However, most venous ulcers have a primary venous origin. The progression rate of VV to higher clinical stages reaches 4% per year. Among the risk factors are obesity and higher age. Quality of life (QOL) is also reduced in uncomplicated VV in C2 patients. In conclusion, there is evidence from the literature that a high proportion of patients with uncomplicated VVs in the clinical, aetiological, anatomical and pathophysiological classification (CEAP Clinical Class 2) will progress to CVI if untreated. VVs have a negative impact on QOL and clinical symptoms. VV patients with CVI (C3-C6) as well as those C2 patients with severe clinical symptoms and impaired QOL due to CVD should be treated with ablation of the VVs in a refunded care system. PMID- 22312064 TI - What is the medical rationale for the treatment of varicose veins? AB - Varicose veins occur in up to one-third of Western populations and are associated with clinical manifestations ranging from asymptomatic, isolated varicose veins (C2 disease) to venous ulceration. While the development of less invasive treatment options, such as endovenous ablation and sclerotherapy, have been well accepted by patients they have led to increased utilization of scarce health-care resources. While few would argue with the treatment of acute complications such as superficial venous thrombosis and variceal haemorrhage, the role of interventional treatment in the management of lifestyle limiting symptoms and the prevention of disease progression may be debatable. Good-quality evidence does suggest that surgical management of varicose veins is associated with improved quality of life at costs below the thresholds of many Western health-care systems. However, the progression of isolated C2 disease to advanced chronic venous insufficiency occurs infrequently and the role of treatment to prevent such progression remains undefined at present. PMID- 22312065 TI - Complications of radiofrequency ablation of varicose veins. AB - Radiofrequency ablation (RFA) has become a valued weapon in the phlebologist's armoury. It offers ease of use and reproducibility with good outcomes. However, as with all interventions, complications arise. In this review we examine the complications inherent with RFA and their relative risk, with their avoidance measures if available. Overall, we find that RFA offers a very safe procedure with rare severe complications. PMID- 22312066 TI - Complications of endovenous lasers. AB - Endovenous laser ablation (EVLA) and radiofrequencey ablation have become the procedures of choice for the treatment of superficial venous insufficiency. Their minimally invasive technique and safety profile when compared with operative saphenectomy have led to this change. As EVLA has replaced saphenectomy as the procedure of choice, the distribution of complications has changed. We evaluated the most common and most devastating complications in the literature including burns, nerve injury, arterio-venous fistula (AVF), endothermal heat-induced thrombosis and deep venous thrombosis. The following review will discuss the most frequently encountered complications of treatment of superficial venous insufficiency using EVLA. The majority of the complications described can be avoided with the use of good surgical technique and appropriate duplex ultrasound guidance. Overall, EVLA has an excellent safety profile and should be considered among the first line for treatment of superficial venous reflux. PMID- 22312067 TI - Complications of foam sclerotherapy. AB - Foam sclerotherapy may result in drug and/or gas-related complications of a generalized or localized nature. Significant complications include anaphylactic/anaphylactoid reactions (very rare), deep vein thrombosis (1-3%), stroke (0.01%), superficial venous thrombosis (4.4%), tissue necrosis (variable frequency), oedema (0.5%) and nerve damage (0.2%). Cosmetic complications include telangiectatic matting (15-24%) and pigmentation (10-30%). Patent foramen ovale and other cardio-pulmonary right-to-left shunts seem to play a role in the systemic gas-related complications. In conclusion, foam sclerotherapy is characterized by an overall high degree of safety, though special attention should be given to the embolic and thrombotic complications. Good technique, adequate imaging, general precautions and compliance with post-treatment instructions may help avoid some of the adverse events and an appropriate early intervention may minimize possible sequelae. Higher volumes of sclerosant foam have been attributed to local and distant thrombotic complications and should be avoided. PMID- 22312068 TI - Pelvic congestion syndrome: a review of current diagnostic and minimally invasive treatment modalities. AB - Chronic pelvic pain is a debilitating medical condition with a host of potential causes. Although often overlooked, pelvic congestion syndrome (PCS) is a well established cause of chronic pelvic pain due to abnormal ovarian and pelvic varices. The diagnosis is established with modern non-invasive cross-sectional imaging, preferably contrast enhanced magnetic resonance imaging. Although medical and open surgical therapies exist, transcatheter percutaneous embolotherapy has been shown to be a safe, effective and durable therapy for the treatment of PCS. Further prospective randomized studies are needed to refine optimal technique and assess long-term patient outcomes. PMID- 22312069 TI - How does the patho-physiology influence the treatment of pelvic congestion syndrome and is the result long-lasting? AB - The objectives of this study are to consider the influence of pathophysiology in the treatment of pelvic congestion syndrome (PCS) and to determine the criteria which impact on the long-term results. A classification of venous pathology including three types of pathophysiological conditions, independent of the location of the pelvic venous pathology, is developed and illustrated. These types, diagnosed by cross-sectional imaging and confirmed by phlebography, are associated with a specific therapeutic plan. The long-term results are dependent on the quality of the initial phlebographic mapping that must be selective and complete, the angiographic findings, in particular the study of collaterals feeding the venous anomalies, the treatment of all venous anomalies, the respect of contraindications, the use of appropriate materials and the occurrence of new pregnancies. In conclusion, the feasibility and satisfactory short-term results of endovascular treatment of PCS are admitted. Questions remain regarding the effectiveness of the different embolic agents and the long-term results of this treatment. PMID- 22312070 TI - Pelvic congestion syndrome can be treated operatively with good long-term results. AB - Pelvic congestion syndrome (PCS) is frequent and underestimated as both symptoms and signs are not specific. Furthermore, patients consult general practitioners as well as specialist gynaecologists, urologists, vascular surgeons and phlebologists who are frequently unaware of this condition. Investigation protocol must first eliminate other diseases with similar clinical disorders and then identify which veins are responsible for PCS related to compression or reflux. Selective venography is the more informative investigation but transvaginal ultrasound examination is a valuable screening test. Outcome analyses after endovenous treatment have been reported in several articles, but no randomized controlled trial is available for comparing various operative treatments knowing that most of them were undertaken after failure of medical treatment. In our experience, about two-thirds of patients were symptom-free after vein compression, stenting, or embolization at middle-term assessment. PMID- 22312071 TI - The outcome of treatment for pelvic congestion syndrome. AB - Pelvic congestion syndrome is one of many causes of chronic pelvic pain. It is generally accepted that this is attributable to ovarian and pelvic vein incompetence which may result in varices in the lower limb leading to presentation in varicose vein clinics. However, far more patients have pelvic varices associated with varicose veins in the lower limb than have pelvic congestion syndrome. Magnetic resonance imaging and computed tomographic venography are usually used in the diagnosis of this condition and criteria have been established to identify pelvic varices. Many different treatments have been used to manage the symptoms of pelvic congestion. Hysterectomy combined with oophrectomy, open surgical ligation of ovarian veins and laparoscopic vein ligation have been used in the past. The most common treatments used currently involve embolization of pelvic and ovarian veins. The results of this treatment have been published in a limited number of clinical series, usually with fairly short follow-up periods. These treatments may be complicated by migration of embolization of coils used to occlude veins. The longest duration of follow-up currently reported is five years. Limited clinical evidence supports the use of embolotherapy in the management of pelvic congestion syndrome. PMID- 22312072 TI - Rationale and indications for aggressive early thrombus removal. AB - Randomized clinical trials have defined anticoagulation with unfractionated or low-molecular-weight heparin followed by warfarin as a standard therapy for acute deep venous thrombosis (DVT). Such treatment is highly effective in preventing recurrent venous thromboembolism with a low risk of bleeding, but provides imperfect protection against development of the post-thrombotic syndrome. Several strategies of early thrombus removal, including surgical venous thrombectomy, catheter-directed thrombolysis and pharmacomechanical thrombectomy have been developed with the goal of reducing the incidence of the post-thrombotic syndrome by restoring venous patency and preserving valvular function. Although clinical judgement and a consideration of the individual patient's medical condition and values are required, early thrombus removal strategies should be considered in selected patients with phlegmasia cerulea dolens and those with a first episode of acute iliofemoral thrombosis of less than 14 days duration. PMID- 22312073 TI - Incidence and risk factors of the post-thrombotic syndrome. AB - Annually 1-2 in every 1000 adults will develop a deep venous thrombosis of the lower extremity. A third to half of these patients will develop the post thrombotic syndrome (PTS). However, predicting which patients will develop the PTS remains elusive. Ipsilateral thrombosis recurrence seems to be the most important risk factor. Moreover, residual venous occlusion and valvular reflux seem to predict PTS incidence to some degree. Laboratory parameters, including d dimers and inflammatory markers, have shown promise in predicting development of the PTS in patients and are currently under investigation. Creating a model based on all combined risk factors and patient characteristics might aid in risk stratification in individual patients. PMID- 22312074 TI - The future of deep venous thrombosis and post-thrombotic syndrome in 2020. AB - This manuscript addresses six major issues involving deep venous thrombosis (DVT) and post-thrombotic syndrome. Prevention will likely see modest advances in pharmacological therapy, mainly by extending prophylaxis in high-risk patients. More notable advances will be observed in mechanical means of prophylaxis, focusing on sustained application of devices that can move larger volumes of blood. Silent, large-vein thrombi continue to place patients at risk for fatal pulmonary embolism. Improved imaging techniques will permit us to identify these patients over the next eight years. In many of those patients, vena caval interruption will be required. Elimination of high-risk filters and the production of improved filters placed through low-profile systems with antithrombotic agents bound to their surface will improve the short- and long term results for inferior vena cava filters. The long-term management of DVT will focus on establishing appropriate duration for the individual patient and will see the evolution towards direct Xa and IIa inhibitors. Patients with extensive DVT will more commonly receive treatment strategies designed to eliminate thrombus and restore patency. This will substantially reduce post-thrombotic morbidity and reduce recurrence. Post-thrombotic syndrome will see greater attention towards treating the intraluminal fibrosis, thereby eliminating post thrombotic venous obstruction. Unfortunately, neovalves will still be searching for the appropriate application. PMID- 22312075 TI - Open and hybrid deep vein reconstructions: to do or not to do? AB - Endovascular reconstruction has become the standard treatment of chronic obstruction of large veins. Stenting is done with increasing frequency to treat iliac venous obstructions, with or without associated inferior vena caval or femoral vein occlusions. Open reconstruction with venous bypass is performed today in patients who fail attempts at venous stenting or who are not candidates for endovascular reconstructions. Patients with primary or secondary malignancies invading the vena cava undergo open caval reconstruction at the time of tumour excision. Open venous reconstructions are still preferred in patients with large vein injuries due to blunt or penetrating trauma or in those who suffer iatrogenic venous injuries. Hybrid reconstruction can be performed with endophlebectomy of the common femoral or femoral veins combined with iliofemoral stenting. PMID- 22312076 TI - Extra- and transcranial echo colour Doppler in the diagnosis of chronic cerebrospinal venous insufficiency. AB - A new venous disorder, chronic cerebrospinal venous insufficiency (CCSVI), has been proposed in patients with multiple sclerosis (MS). It is a vascular condition characterized by an impaired cerebrospinal venous drainage due to obstructions in the main extracranial cerebrovenous outflow routes (i.e. internal jugular veins [IJV] and/or azygos veins). In this review, the studies which assessed the prevalence of CCSVI in MS by echo colour Doppler (ECD) will be discussed. The technical aspects of determination of the five CCSVI criteria: (1) reflux in the IJV and/or vertebral veins in supine and upright position, (2) reflux in the deep cerebral veins, (3) high-resolution B-mode proximal IJV stenosis, (4) flow not Doppler detectable in IJVs and/or vertebral veins (VVs) and (5) reverted postural control of the main cerebrovenous outflow pathway are described in detail. We conclude that so far there are many studies with contradictory results, and as yet a strong scientific base to support the evidence for a causative relationship of CCSVI and MS is lacking. Recent studies call into question the validity of using ECD as a proper and reliable test for the diagnosis of CCSVI. One explanation for the variety in interpretation of the individual CCSVI criteria, with the wide-ranging percentages CCSVI, could be the different methods by using ECD to determine various criteria. PMID- 22312077 TI - Clinical, aetiological, anatomical and pathological classification (CEAP): gold standard and limits. AB - The first CEAP (clinical, aetiological, anatomical and pathological elements) consensus document was published after a consensus conference of the American Venous Forum, held at the sixth annual meeting of the AVF in February 1994 in Maui, Hawaii. In the following years the CEAP classification was published in many international journals and books which has led to widespread international use of the CEAP classification since 1995. The aim of this paper is to review the benefits and limits of CEAP from the available literature. In an actual Medline analysis with the keywords 'CEAP' and 'venous insufficiency', 266 publications using the CEAP classification in venous diseases are available. The CEAP classification was accepted in the venous community and used in scientific publications, but in most of the cases only the clinical classification was used. Limitations of the first version including a lack of clear definition of clinical signs led to a revised version. The CEAP classification is the gold standard of classification of chronic venous disorders today. Nevertheless for proper use some facts have to be taken into account: the CEAP classification is not a severity classification, C2 summarizes all kinds of varicose veins, in C3 it may be difficult to separate venous and other reasons for oedema, and corona phlebectatica is not included in the classification. Further revisions of the CEAP classification may help to overcome the still-existing deficits. PMID- 22312078 TI - Revised venous clinical severity score: a facile measurement of outcomes in venous disease. AB - Outcome assessment is an important criterion for the objective determination of the risks and benefits of a given procedure. The choice of an assessment instrument is critical in order to generate meaningful and relevant data. Assessment instruments are platforms for comparison and stratification of information that provide a common ground and unified language for discussions on disease processes and therapies. Like many complex conditions, venous disease has benefited from the institution of several assessment instruments designed to clarify elements of the disease process. Among these is the venous clinical severity score (VCSS), which has proved to be a valuable tool for evaluating changes in condition over time with or without intervention. The VCSS has recently undergone a revision to increase its sensitivity and value in interpreting the language of venous disease. PMID- 22312079 TI - Villalta scale: goals and limitations. AB - The post-thrombotic syndrome (PTS) is a common, debilitating complication following deep venous thrombosis. PTS is a syndrome for which it has been difficult to provide a clear definition. PTS was defined as chronic venous signs/symptoms after a deep venous thrombosis. A number of scales are available to diagnose PTS, but there is a strong need for standardization. The Villalta scale was chosen as the standardized PTS scale. The Villalta scale has been validated in several studies and shows good correlation with generic and disease specific quality of life scales. The inter-observer rate between study nurses and physicians was shown to be very good. Furthermore, the scale shows good discriminative properties among the different severity groups of PTS. The Villalta scale is useful for use in randomized controlled trials and it allows pooling of data from different studies. The Villalta scale should undergo further validation on intra-rater reliability. Ongoing randomized controlled trials will further validate the Villalta scale for use in PTS. PMID- 22312080 TI - Importance of patient-reported outcomes in chronic venous disorders. AB - The assessment of outcomes following treatment for chronic venous disease has been greatly improved over the last three decades. The personal opinion of the physician based on assessment of his own results has been replaced by more objective assessment based on well-defined criteria. The author describes and compares a number of different methods currently in use for this purpose. PMID- 22312081 TI - Lymphatic complications after varicose veins surgery: risk factors and how to avoid them. AB - INTRODUCTION: Lymphatic complication (LC) after varicose veins (VVs) surgery is an annoying event with a variable frequency in the literature. METHOD: Retrospective study reviewing all surgeries carried out for VVs from January 2000 to October 2010. Postoperative LC we reported: lymphatic fistula, lymphocele including the minor ones and lymphoedema. RESULTS: During the period studied, 5407 surgical procedures for VVs were performed in 3407 patients (74.7% women) with a mean age of 53.4 years. A postoperative LC occurred in 118 cases (2.2%): lymphocele on limb in 1.3%, inguinal LC (fistula or lymphocele) in 0.7% and a lymphoedema in 0.2%. The population with a LC was older (59.6 vs. 53.3 years, P < 0.05), had a higher frequency of C4-C6 (22.0% vs. 6.5%, P < 0.05), a higher incidence of obesity (31.4% vs. 5.4%, P < 0.05) and was more often treated by a redo surgery or a crossectomy stripping (48.3% vs. 13.4% and 38.1% vs. 21.8%, respectively, P < 0.05). We have observed a dramatic decrease in incidence of LC after January 2004 (1.3% vs. 5.3%, P < 0.05) corresponding to a new surgical practice for the treatment of VVs: stripping, crossectomy and redo surgery at the groin were less frequent (74.6% vs. 7.7%, 74.6% vs. 0.2% and 11.3% vs. 0.1%, respectively, P < 0.05), while isolated phlebectomy was more often performed during this period (78.4% vs. 8.4%, P < 0.05). CONCLUSION: LC after VVs surgery is not rare but frequently limited to lymphocele on limbs. Older age, more advanced clinical stage and obesity were associated with a higher frequency of LC. A mini-invasive and selective surgery has significantly reduced the occurrence of LC. PMID- 22312082 TI - An imaging approach to deep vein thrombosis and the lower extremity thrombosis classification. AB - In this article we want to discuss the potential of lower extremity deep vein thrombosis (DVT) imaging and propose a systematic approach to DVT management based on a DVT classification of the lower extremity; the LET classification. Identifying and reporting DVT more systematically allows for accurate stratification for initial patient care, future clinical trials and appropriate descriptions for natural history studies. PMID- 22312083 TI - Safety and efficacy of catheter-directed thrombolysis. AB - OBJECTIVE: To describe the background for--and mechanism of--catheter-directed thrombolysis (CDT) for iliofemoral deep venous thrombosis (DVT) accessed via the popliteal vein. Focus is on safety and efficacy. METHOD: From the Copenhagen experience we have looked into the systematically registrated risk factors, peri- and postprocedure complications for patients consecutively treated from 1999 to 2006. The patients were treated in a clinical ward. The patients were followed yearly with ultrasonography for assessment of patency and valve function. Inclusion and exclusion criteria have been published earlier. RESULTS: A total of 89 patients with 91 extremities with iliofemoral DVT were included (70 women and 19 men, mean age 29 years [range 14-59]). Only 11% of the patients were without any risk factor for DVT. CDT was performed without mortality and pulmonary embolism. Major bleeding occurred in two patients and minor bleeding in 27 patients, mostly from the puncture site. Stenting was necessary in 54 limbs. Five stents revealed occlusion, three procedural (2 reopened) and two late. The median follow-up was 87 months (range 17-148). At six years, 86% had competent iliofemoral (and popliteal) vein segment. CONCLUSION: CDT of iliofemoral DVT is a safe procedure. The patients can stay in a clinical vascular ward. The long-term efficacy is still durable in producing competent veins as concluded in our earlier published results. PMID- 22312084 TI - Pharmaco-mechanical thrombectomy for early thrombus removal. AB - OBJECTIVES: To review the current literature on the outcomes of pharmaco mechanical thrombectomy (PMT) for early thrombus removal in patients with venous thromboembolism (VTE). METHODS: We searched the MEDLINE database and performed a manual search of the references of selected articles to select reports reporting the outcomes of PMT alone and PMT compared to catheter-direct thrombolysis (CDT). Outcomes of interest included clot lysis rate, incidence of pulmonary embolism, major bleeding, recurrent deep vein thrombosis, number of venograms needed and amount of lytic utilized. RESULTS: We found nine articles that reported outcomes of PMT. Three devices were utilized for PMT, the Angiojet, Trellis and Helix. Different thrombolytics were used to facilitate thrombus removal including urokinase, reteplase, tecneteplase, and tissue plasminogen activator (t-PA). Complete and partial thrombus removal were achieved in up to 84% and 64% and 81% and 59% of the limbs treated with PMT and CDT alone, respectively. Data on PE and bleeding risk after PMT compared to CDT are scarce. The duration of the thrombolysis process, amount of lytics and number of venograms were substantially reduced in the patients who had PMT compared to those who underwent CDT alone. Two articles evaluated the obstacles that limit the indication of PMT in patients with VTE. CONCLUSION: VTE is a prevalent burden in Western societies. The rationale of early thrombus is to reduce valvular damage and improve venous patency in order to reduce the risk of PTS. PMT is a feasible, safe and faster alternative to expedite the thrombolysis process in patients with VTE. PMID- 22312085 TI - A novel scoring system for lower-extremity venous pathology analysed using magnetic resonance venography and duplex ultrasound. AB - OBJECTIVES: To present a novel scoring system for lower-extremity venous pathology (the LOVE score) and our experiences using it in our clinical practice to identify venous pathology with duplex ultrasound (DUS) and magnetic resonance venography (MRV). METHOD: A total of 40 patients, 30 suspected of chronic venous disease and 10 with acute deep vein thrombosis (DVT) were examined from the inferior vena cava (IVC) to the popliteal vein using DUS and MRV. The image findings were reported using the LOVE score. RESULTS: The majority of deep veins (368 out of 378 segments) were completely visualized by both our imaging techniques and could be analysed using the LOVE score. Both imaging techniques reported comparable findings with regard to the visualization of thrombus, obstruction, collaterals, trabeculations, anatomic variations and central venous compression (e.g. May-Thurner). CONCLUSIONS: The LOVE score can be used to expand and standardize the documentation of imaging the deep venous system beyond thrombosis, to help identify (optimal) treatment options in patients with venous disease, in both the clinical and research setting. This first assessment shows that both DUS and MRV are capable of systematically identifying a multitude of changes in the venous system. PMID- 22312086 TI - Endovascular treatment options for chronic venous obstructions. AB - Chronic venous obstructions have been treated by means of bypass surgery, until, in recent decades, it was surpassed by endovascular treatment options. Although techniques may differ, some issues should be universal. It is recommended that patients are treated under general anaesthesia. Secondly, obstructive lesions should be fully stented. Finally, self-expandable stents should mainly be used. Recanalization and stenting proved safe and efficient with excellent mid- and long-term patency rates. However, failures due to re-occlusion do occur and are basically related to imperfect stent design and/or suboptimal inflow. Therefore, the main focus should be on the development of optimal stent configuration, that is, sufficient length, highest possible radial force and flexibility. Moreover, the significance of endophlebectomy with or without creation of an arteriovenous fistula should be established. PMID- 22312087 TI - The hypothesis of patho-physiological correlation between chronic cerebrospinal venous insufficiency and multiple sclerosis: rationale of treatment. AB - BACKGROUND: The possible role of the venous system in the pathogenesis of chronic neurodegenerative diseases has been hypothesized for decades. Quite recently, the description of a venous condition defined as chronic cerebrospinal venous insufficiency (CCSVI) and its strong association with multiple sclerosis (MS) has brought back the attention of the scientific community to the hypothesis of an aetiological or concomitant role of an altered venous function in the occurrence of this pathology. CCSVI is identified by sonographic criteria, thus the indication for its possible treatment is based on ultrasound findings. METHOD: We retrospectively examined 167 consecutive patients affected by clinically defined MS and CCSVI, identified by ultrasound assessment by the presence of at least two sonographic criteria. Ultrasonographic diagnosis of CCSVI was then integrated by venography and intravascular ultrasound examination (in 43 patients). Patients were all submitted to endovascular procedure (venoplasty). RESULTS: In 37% of cases there was no correspondence between the preoperative ultrasound assessment and the venographic findings. In the event of incongruity between venography and sonography, the intravascular ultrasound examination investigation, when performed, confirmed ultrasound findings in 42% of cases and venography results in 58%. At one month in 12% of cases ultrasound assessment showed the persistence of altered flux. In 67% of cases patients reported subjective amelioration, regarding non-specific symptoms. CONCLUSION: The pathophysiology of CCSVI is yet to be defined. The superior cava venous system is highly complex in terms of anatomy and possible anomalies, as well as its haemodynamic mechanisms. Further studies are required to define the parameters of diagnosis and treatment of CCSVI. PMID- 22312088 TI - Evolution in quality of life and epidemiological impact after endovascular treatment of chronic cerebro-spinal venous insufficiency in patients with multiple sclerosis. AB - BACKGROUND: We report the outcome of 67 patients after endovascular treatment of chronic cerebro-spinal venous insufficiency in patients with multiple sclerosis. Material and methods For evaluating outcome, patients were divided into three groups with respective outcome after three, six and twelve months. Assessment of outcome was done by a disease-specific quality-of-life score that reflects the physical health (physical health composite, PHC) and mental health (mental health composite, MHC) by a score. RESULTS: Improvement in PHC was significant (P < 0.05) in the three- and six-month groups. Improvement in MHC was only significant (P < 0.05) in the three-month group. CONCLUSION: In conclusion, we can state that the result of endovascular treatment seems to decay although the baseline is still higher than preoperative. To confirm this finding, this study needs to be reproduced in a larger patient population. PMID- 22312089 TI - Approach to the patient with postpartum thyroiditis. AB - Postpartum thyroiditis (PPT) is the occurrence of de novo autoimmune thyroid disease, excluding Graves' disease, in the first year postpartum. The incidence of PPT is 5.4% in the general population, and it is increased in individuals with other autoimmune diseases such as type 1 diabetes mellitus. The classic presentation of PPT of hyperthyroidism followed by hypothyroidism is seen in 22% of cases. The majority of women with PPT experience an isolated hypothyroid phase (48%), with the remainder experiencing isolated thyrotoxicosis (30%). Up to 50% of women who are thyroid antibody positive (thyroid peroxidase antibody and/or thyroglobulin antibody) in the first trimester will develop PPT. Symptoms are more common in the hypothyroid phase of PPT and include fatigue, dry skin, and impaired memory. Despite multiple studies exploring the relationship between PPT and postpartum depression, or postpartum depression in thyroid antibody-positive euthyroid women, the data are conflicting, and no firm conclusions can be reached. Long-term follow-up of women who had an episode of PPT reveals a 20-40% incidence of permanent primary hypothyroidism. In a single study, selenium administration significantly decreased the incidence of PPT, but replication of the findings is needed before the recommendation can be made that all pregnant thyroid peroxidase antibody-positive women receive selenium. The indication for treating the hyperthyroid phase of PPT is control of symptoms, whereas treatment of the hypothyroid phase of PPT is indicated for symptomatic relief as well as in women who are either breastfeeding or attempting to conceive. PMID- 22312090 TI - The platform for adipose tissue expansion during positive energy balance. PMID- 22312091 TI - Reports of increased mortality and GH: will this affect current clinical practice? PMID- 22312092 TI - A new look at vitamin D metabolism and "idiopathic" hypercalcemia. PMID- 22312093 TI - Adrenocortical cancer in Carney complex: a paradigm of endocrine tumor progression or an association of genetic predisposing factors? PMID- 22312098 TI - Glucocorticoid-induced osteoporosis. PMID- 22312100 TI - Dose-adjusted EPOCH-rituximab combined with fludarabine provides an effective bridge to reduced-intensity allogeneic hematopoietic stem-cell transplantation in patients with lymphoid malignancies. AB - PURPOSE: There is currently no standard chemotherapy regimen for patients with lymphoid malignancies being considered for reduced-intensity conditioning allogeneic hematopoietic stem-cell transplantation (RIC-alloHSCT). The ideal regimen would provide disease control and result in lymphocyte depletion to facilitate engraftment. To this end, we developed a novel regimen by adding fludarabine to dose-adjusted continuous-infusion etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus with or without rituximab (DA EPOCH-F/R). PATIENTS AND METHODS: One hundred forty-seven patients with lymphoid malignancy (median age, 50 years) who had heavily pretreated (median prior regimens, three) and chemo-refractory (47%) disease were treated with DA-EPOCH F/R before RIC-alloHSCT. Patients received one to three consecutive cycles until achieving lymphocyte depletion (CD4(+) count < 200/MUL) or progressive disease. RESULTS: Overall response rate was 41%; 39% of patients had stable disease. Toxicity included grade 4 neutropenia in 65% and thrombocytopenia in 25% of patients. DA-EPOCH-F/R resulted in lymphocyte depletion (P < .001), which was inversely associated with serum interleukin (IL) 7 and IL-15 levels. Of 147 patients, 143 patients proceeded to RIC-alloHSCT. Patients with lower CD3(+) (P < .001), CD4(+) (P < .001), and CD8(+) (P < .001) T-cell counts after DA-EPOCH-F/R were more likely to achieve full donor lymphoid chimerism by day +14 after transplant. Relative to nonresponders to DA-EPOCH-F/R, patients with complete and partial response had increased event-free survival (77.4 v 4.8 months; P < .001) and overall survival (98.5 v 16.2 months; P < .001). CONCLUSION: DA-EPOCH-F/R safely provides tumor cytoreduction and lymphocyte depletion, thereby offering a bridge to RIC-alloHSCT in patients with aggressive lymphoid malignancies. PMID- 22312101 TI - American Society of Clinical Oncology provisional clinical opinion: the integration of palliative care into standard oncology care. AB - PURPOSE: An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) offers timely clinical direction to ASCO's membership following publication or presentation of potentially practice-changing data from major studies. This PCO addresses the integration of palliative care services into standard oncology practice at the time a person is diagnosed with metastatic or advanced cancer. CLINICAL CONTEXT: Palliative care is frequently misconstrued as synonymous with end-of-life care. Palliative care is focused on the relief of suffering, in all of its dimensions, throughout the course of a patient's illness. Although the use of hospice and other palliative care services at the end of life has increased, many patients are enrolled in hospice less than 3 weeks before their death, which limits the benefit they may gain from these services. By potentially improving quality of life (QOL), cost of care, and even survival in patients with metastatic cancer, palliative care has increasing relevance for the care of patients with cancer. Until recently, data from randomized controlled trials (RCTs) demonstrating the benefits of palliative care in patients with metastatic cancer who are also receiving standard oncology care have not been available. RECENT DATA: Seven published RCTs form the basis of this PCO. PROVISIONAL CLINICAL OPINION: Based on strong evidence from a phase III RCT, patients with metastatic non-small-cell lung cancer should be offered concurrent palliative care and standard oncologic care at initial diagnosis. While a survival benefit from early involvement of palliative care has not yet been demonstrated in other oncology settings, substantial evidence demonstrates that palliative care-when combined with standard cancer care or as the main focus of care-leads to better patient and caregiver outcomes. These include improvement in symptoms, QOL, and patient satisfaction, with reduced caregiver burden. Earlier involvement of palliative care also leads to more appropriate referral to and use of hospice, and reduced use of futile intensive care. While evidence clarifying optimal delivery of palliative care to improve patient outcomes is evolving, no trials to date have demonstrated harm to patients and caregivers, or excessive costs, from early involvement of palliative care. Therefore, it is the Panel's expert consensus that combined standard oncology care and palliative care should be considered early in the course of illness for any patient with metastatic cancer and/or high symptom burden. Strategies to optimize concurrent palliative care and standard oncology care, with evaluation of its impact on important patient and caregiver outcomes (eg, QOL, survival, health care services utilization, and costs) and on society, should be an area of intense research. NOTE: ASCO's provisional clinical opinions (PCOs) reflect expert consensus based on clinical evidence and literature available at the time they are written and are intended to assist physicians in clinical decision making and identify questions and settings for further research. Because of the rapid flow of scientific information in oncology, new evidence may have emerged since the time a PCO was submitted for publication. PCOs are not continually updated and may not reflect the most recent evidence. PCOs cannot account for individual variation among patients and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It is the responsibility of the treating physician or other health care provider, relying on independent experience and knowledge of the patient, to determine the best course of treatment for the patient. Accordingly, adherence to any PCO is voluntary, with the ultimate determination regarding its application to be made by the physician in light of each patient's individual circumstances. ASCO PCOs describe the use of procedures and therapies in clinical trials and cannot be assumed to apply to the use of these interventions in the context of clinical practice. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of ASCO's PCOs, or for any errors or omissions. PMID- 22312102 TI - Meeting the decision-making preferences of patients with breast cancer in oncology consultations: impact on decision-related outcomes. AB - PURPOSE: To investigate how involvement preferences of patients with breast cancer change during the treatment decision-making process and determine the impact of meeting patients' expectations on decision-making outcomes. PATIENTS AND METHODS: Participants were 683 patients with breast cancer from 62 oncologists in five different countries recruited to an International Breast Cancer Study Group (IBCSG 33-03) project. Questionnaires elicited patients' pre- and postconsultation preferences for involvement in treatment decision making and whether these were met or not. Decision-related outcomes were assessed postconsultation. RESULTS: Before the consultation, most patients preferred shared or patient-directed treatment decision making. After the consultation, 43% of patients' preferences changed, and most shifted toward patient-directed decisions. The actual postconsultation decision was more likely to be made according to postconsultation rather than preconsultation preferences. Compared with patients who were less involved than they had hoped to be, patients who were as involved as they had hoped to be or were even more involved in decision making had significantly better decision-related outcomes. This was true regardless of whether preference change occurred. CONCLUSION: Many patients with early-stage breast cancer have treatment options and approach treatment decisions with a desire for decisional control, which may increase after their consultation. Patients' ultimate involvement preferences were more likely to be consistent with the way the decision was actually made, suggesting that patients need to feel concordance between their preference and the actual decision. Patients who directed decisions, even if more than they hoped for, fared better on all decision-related outcomes. These results emphasize the need for oncologists to endorse and facilitate patient participation in treatment decision making. PMID- 22312103 TI - Short, full-dose adjuvant chemotherapy in high-risk adult soft tissue sarcomas: a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group. AB - PURPOSE: A previous randomized clinical trial by the Italian Sarcoma Group (ISG) had shown a survival benefit of adjuvant chemotherapy (CT) in high-risk extremity soft tissue sarcoma (STS). However, the dose-intensity of the last two cycles was suboptimal. We then undertook a multicentric international phase III study to compare three and five cycles of the same CT. PATIENTS AND METHODS: Patients were randomly assigned either to receive three cycles of preoperative CT with epirubicin 120 mg/m(2) and ifosfamide 9 g/m(2) and granulocyte colony-stimulating factor (arm A) or to receive the same three cycles of preoperative CT followed by two further cycles of postoperative CT (arm B). Noninferiority of the primary end point, overall survival (OS), was assessed by the CI of the hazard ratio (HR; arm A/arm B) obtained from the Cox model. RESULTS: Between January 2002 and April 2007, 328 patients were recruited (164 patients in each arm). At a median follow up of 63 months (interquartile range, 49 to 77 months), 100 deaths were recorded, 49 in arm A and 51 in arm B. Five-year OS probability was 0.70 for the entire group of patients (0.68 in arm A and 0.71 in arm B). The HR of arm A versus arm B was 1.00 (90% CI, 0.72 to 1.39). CONCLUSION: In this population of patients with high-risk localized STS, three cycles of full-dose preoperative CT were not inferior to five cycles. The outcome compares favorably with the expected survival of patients with high-risk STS and was superimposable on the CT arm of the previous ISG trial. PMID- 22312105 TI - Meta-analysis of randomized controlled trials for the incidence and risk of treatment-related mortality in patients with cancer treated with vascular endothelial growth factor tyrosine kinase inhibitors. AB - PURPOSE: Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have become the cornerstone in the treatment of several malignancies. These drugs have also been associated with an increase in the risk of potentially life-threatening adverse events, such as arterial thrombotic events, bleeding, congestive heart failure, and others. We performed an up-to date meta-analysis to determine the risk of fatal adverse events (FAEs) in patients with cancer treated with VEGFR TKIs. METHODS: MEDLINE and PubMed databases were searched for articles published from January 1966 to February 2011. Eligible studies were limited to trials of US Food and Drug Administration approved VEGFR TKIs (pazopanib, sunitinib, and sorafenib) that reported on patients with cancer with any primary tumor type, randomized design, and adequate safety profile. Statistical analyses were conducted to calculate the summary incidence, relative risk (RR), and 95% CIs by using random-effects or fixed effects models on the basis of the heterogeneity of included studies. RESULTS: In all, 4,679 patients from 10 randomized controlled trials (RCTs) were included, with 2,856 from sorafenib, 1,388 from sunitinib, and 435 from pazopanib trials. The incidence of FAEs related to VEGFR TKIs was 1.5% (95% CI, 0.8% to 2.4%) with an RR of 2.23 (95% CI, 1.12 to 4.44; P = .023) compared with control patients. On subgroup analysis, no difference in the rate of FAEs was found between different VEGFR TKIs or tumor types. No evidence of publication bias was observed. CONCLUSION: In a meta-analysis of RCTs, the use of VEGFR TKIs was associated with an increased risk of FAEs compared with control patients. PMID- 22312106 TI - Uptake and economic impact of first-cycle colony-stimulating factor use during adjuvant treatment of breast cancer. AB - PURPOSE: In 2002, pegfilgrastim was approved by the US Food and Drug Administration and the benefits of dose-dense breast cancer chemotherapy, especially for hormone receptor (HR) -negative tumors, were reported. We examined first-cycle colony-stimulating factor use (FC-CSF) before and after 2002 and estimated US expenditures for dose-dense chemotherapy. METHODS: We identified patients in Surveillance, Epidemiology, and End Results-Medicare greater than 65 years old with stages I to III breast cancer who had greater than one chemotherapy claim within 6 months of diagnosis(1998 to 2005) and classified patients with an average cycle length less than 21 days as having received dose dense chemotherapy. The associations of patient, tumor, and physician-related factors with the receipt of any colony-stimulating factor (CSF) and FC-CSF use were analyzed by using generalized estimating equations. CSF costs were estimated for patients who were undergoing dose-dense chemotherapy. RESULTS: Among the 10,773 patients identified, 5,266 patients (48.9%) had a CSF claim. CSF use was stable between 1998 and 2002 and increased from 36.8% to 73.7% between 2002 and 2005, FC-CSF use increased from 13.2% to 67.9%, and pegfilgrastim use increased from 4.1% to 83.6%. In a multivariable analysis, CSF use was associated with age and chemotherapy type and negatively associated with black/Hispanic race, rural residence, and shorter chemotherapy duration. FC-CSF use was associated with high socioeconomic status but not with age or race/ethnicity. The US annual CSF expenditure for women with HR-positive tumors treated with dose-dense chemotherapy is estimated to be $38.8 million. CONCLUSION: A rapid increase in FC CSF use occurred over a short period of time, which was likely a result of the reported benefits of dose-dense chemotherapy and the ease of pegfilgrastim administration. Because of the increasing evidence that elderly HR-positive patients do not benefit from dose-dense chemotherapy, limiting pegfilgrastim use would combat the increasing costs of cancer care. PMID- 22312107 TI - Wiser use of dose-dense adjuvant therapy in breast cancer. PMID- 22312108 TI - Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study. AB - PURPOSE: Adult T-cell leukemia-lymphoma (ATL) is usually resistant to conventional chemotherapies, and there are few other treatment options. Because CC chemokine receptor 4 (CCR4) is expressed on tumor cells from most patients with ATL, KW-0761, a humanized anti-CCR4 monoclonal antibody, which markedly enhances antibody-dependent cellular cytotoxicity, was evaluated in the treatment of patients with relapsed ATL. PATIENTS AND METHODS: A multicenter phase II study of KW-0761 for patients with relapsed, aggressive CCR4-positive ATL was conducted to evaluate efficacy, pharmacokinetic profile, and safety. The primary end point was overall response rate, and secondary end points included progression-free and overall survival from the first dose of KW-0761. Patients received intravenous infusions of KW-0761 once per week for 8 weeks at a dose of 1.0 mg/kg. RESULTS: Of 28 patients enrolled onto the study, 27 received at least one infusion of KW 0761. Objective responses were noted in 13 of 26 evaluable patients, including eight complete responses, with an overall response rate of 50% (95% CI, 30% to 70%). Median progression-free and overall survival were 5.2 and 13.7 months, respectively. The mean half-life period after the eighth infusion was 422 +/- 147 hours (+/- standard deviation). The most common adverse events were infusion reactions (89%) and skin rashes (63%), which were manageable and reversible in all cases. CONCLUSION: KW-0761 demonstrated clinically meaningful antitumor activity in patients with relapsed ATL, with an acceptable toxicity profile. Further investigation of KW-0761 for treatment of ATL and other T-cell neoplasms is warranted. PMID- 22312109 TI - Cernunnos influences human immunoglobulin class switch recombination and may be associated with B cell lymphomagenesis. AB - Cernunnos is involved in the nonhomologous end-joining (NHEJ) process during DNA double-strand break (DSB) repair. Here, we studied immunoglobulin (Ig) class switch recombination (CSR), a physiological process which relies on proper repair of the DSBs, in B cells from Cernunnos-deficient patients. The pattern of in vivo generated CSR junctions is altered in these cells, with unusually long microhomologies and a lack of direct end-joining. The CSR junctions from Cernunnos-deficient patients largely resemble those from patients lacking DNA ligase IV, Artemis, or ATM, suggesting that these factors are involved in the same end-joining pathway during CSR. By screening 269 mature B cell lymphoma biopsies, we also identified a somatic missense Cernunnos mutation in a diffuse large B cell lymphoma sample. This mutation has a dominant-negative effect on joining of a subset of DNA ends in an in vitro NHEJ assay. Translocations involving both Ig heavy chain loci and clonal-like, dynamic IgA switching activities were observed in this tumor. Collectively, our results suggest a link between defects in the Cernunnos-dependent NHEJ pathway and aberrant CSR or switch translocations during the development of B cell malignancies. PMID- 22312110 TI - Gene expression induced by Toll-like receptors in macrophages requires the transcription factor NFAT5. AB - Toll-like receptors (TLRs) engage networks of transcriptional regulators to induce genes essential for antimicrobial immunity. We report that NFAT5, previously characterized as an osmostress responsive factor, regulates the expression of multiple TLR-induced genes in macrophages independently of osmotic stress. NFAT5 was essential for the induction of the key antimicrobial gene Nos2 (inducible nitric oxide synthase [iNOS]) in response to low and high doses of TLR agonists but is required for Tnf and Il6 mainly under mild stimulatory conditions, indicating that NFAT5 could regulate specific gene patterns depending on pathogen burden intensity. NFAT5 exhibited two modes of association with target genes, as it was constitutively bound to Tnf and other genes regardless of TLR stimulation, whereas its recruitment to Nos2 or Il6 required TLR activation. Further analysis revealed that TLR-induced recruitment of NFAT5 to Nos2 was dependent on inhibitor of kappaB kinase (IKK) beta activity and de novo protein synthesis, and was sensitive to histone deacetylases. In vivo, NFAT5 was necessary for effective immunity against Leishmania major, a parasite whose clearance requires TLRs and iNOS expression in macrophages. These findings identify NFAT5 as a novel regulator of mammalian anti-pathogen responses. PMID- 22312111 TI - The 2'-O-methylation status of a single guanosine controls transfer RNA-mediated Toll-like receptor 7 activation or inhibition. AB - Foreign RNA serves as pathogen-associated molecular pattern (PAMP) and is a potent immune stimulator for innate immune receptors. However, the role of single bacterial RNA species in immune activation has not been characterized in detail. We analyzed the immunostimulatory potential of transfer RNA (tRNA) from different bacteria. Interestingly, bacterial tRNA induced type I interferon (IFN) and inflammatory cytokines in mouse dendritic cells (DCs) and human peripheral blood mononuclear cells (PBMCs). Cytokine production was TLR7 dependent because TLR7 deficient mouse DCs did not respond and TLR7 inhibitory oligonucleotides inhibited tRNA-mediated activation. However, not all bacterial tRNA induced IFN alpha because tRNA from Escherichia coli Nissle 1917 and Thermus thermophilus were non-immunostimulatory. Of note, tRNA from an E. coli knockout strain for tRNA (Gm18)-2'-O-methyltransferase (trmH) regained immunostimulatory potential. Additionally, in vitro methylation of this immunostimulatory Gm18-negative tRNA with recombinant trmH from T. thermophilus abolished its IFN-alpha inducing potential. More importantly, Gm18-modified tRNA acted as TLR7 antagonist and blocked IFN-alpha induction of influenza A virus-infected PBMCs. PMID- 22312112 TI - Self-reactive human CD4 T cell clones form unusual immunological synapses. AB - Recognition of self-peptide-MHC (pMHC) complexes by CD4 T cells plays an important role in the pathogenesis of many autoimmune diseases. We analyzed formation of immunological synapses (IS) in self-reactive T cell clones from patients with multiple sclerosis and type 1 diabetes. All self-reactive T cells contained a large number of phosphorylated T cell receptor (TCR) microclusters, indicative of active TCR signaling. However, they showed little or no visible pMHC accumulation or transport of TCR-pMHC complexes into a central supramolecular activation cluster (cSMAC). In contrast, influenza-specific T cells accumulated large quantities of pMHC complexes in microclusters and a cSMAC, even when presented with 100-fold lower pMHC densities. The self-reactive T cells also maintained a high degree of motility, again in sharp contrast to virus-specific T cells. 2D affinity measurements of three of these self-reactive T cell clones demonstrated a normal off-rate but a slow on-rate of TCR binding to pMHC. These unusual IS features may facilitate escape from negative selection by self-reactive T cells encountering very small amounts of self-antigen in the thymus. However, these same features may enable acquisition of effector functions by self-reactive T cells encountering large amounts of self-antigen in the target organ of the autoimmune disease. PMID- 22312113 TI - Identification of modifications in microbial, native tRNA that suppress immunostimulatory activity. AB - Naturally occurring nucleotide modifications within RNA have been proposed to be structural determinants for innate immune recognition. We tested this hypothesis in the context of native nonself-RNAs. Isolated, fully modified native bacterial transfer RNAs (tRNAs) induced significant secretion of IFN-alpha from human peripheral blood mononuclear cells in a manner dependent on TLR7 and plasmacytoid dendritic cells. As a notable exception, tRNA(Tyr) from Escherichia coli was not immunostimulatory, as were all tested eukaryotic tRNAs. However, the unmodified, 5'-unphosphorylated in vitro transcript of tRNA(Tyr) induced IFN-alpha, thus revealing posttranscriptional modifications as a factor suppressing immunostimulation. Using a molecular surgery approach based on catalytic DNA, a panel of tRNA(Tyr) variants featuring differential modification patterns was examined. Out of seven modifications present in this tRNA, 2'-O-methylated G(m)18 was identified as necessary and sufficient to suppress immunostimulation. Transplantation of this modification into the scaffold of yeast tRNA(Phe) also resulted in blocked immunostimulation. Moreover, an RNA preparation of an E. coli trmH mutant that lacks G(m)18 2'-O-methyltransferase activity was significantly more stimulatory than the wild-type sample. The experiments identify the single methyl group on the 2'-oxygen of G(m)18 as a natural modification in native tRNA that, beyond its primary structural role, has acquired a secondary function as an antagonist of TLR7. PMID- 22312114 TI - Programmed cell death induced by high levels of cytokinin in Arabidopsis cultured cells is mediated by the cytokinin receptor CRE1/AHK4. AB - High levels of cytokinins (CKs) induce programmed cell death (PCD) both in animals and plant cells. High levels of the CK benzylaminopurine (BA) induce PCD in cultured cells of Arabidopsis thaliana by accelerating a senescence process characterized by DNA laddering and expression of a specific senescence marker. In this report, the question has been addressed whether members of the small family of Arabidopsis CK receptors (AHK2, AHK3, CRE1/AHK4) are required for BA-induced PCD. In this respect, suspension cell cultures were produced from selected receptor mutants. Cell growth and proliferation of all receptor mutant and wild type cell cultures were similar, showing that the CK receptors are not required for these processes in cultured cells. The analysis of CK metabolites instead revealed differences between wild-type and receptor mutant lines, and indicated that all three receptors are redundantly involved in the regulation of the steady state levels of isopentenyladenine- and trans-zeatin-type CKs. By contrast, the levels of cis-zeatin-type CKs were controlled mainly by AHK2 and AHK3. To study the role of CK receptors in the BA-induced PCD pathway, cultured cells were analysed for their behaviour in the presence of high levels of BA. The results show that CRE1/AHK4, the strongest expressed CK receptor gene of this family in cultured cells, is required for PCD, thus linking this process to the known CK signalling pathway. PMID- 22312115 TI - Blue light signalling in chloroplast movements. AB - Chloroplast movements are among the mechanisms allowing plants to cope with changes in their environment. Chloroplasts accumulate at illuminated cell areas under weak light while they avoid areas exposed to strong light. These directional responses may be controlled by blue and/or red light, depending on the plant group. In terrestrial angiosperms only the blue light perceived by phototropins is active. The last decade has seen a rapid development of studies on the mechanism of directional chloroplast movements, which started with an identification of the photoreceptors. A forward genetic approach has been used to identify the components which control chloroplast movements. This review summarizes the current state of research into the signalling pathways which lead to chloroplast responses. First, the molecular properties of phototropins are presented, followed by a characterization both of proteins which are active downstream of phototropins and of secondary messengers. Finally, cross-talk between light signalling involved in chloroplast movements and other signalling pathways is discussed. PMID- 22312116 TI - Applications of next-generation sequencing in plant biology. AB - The last several years have seen revolutionary advances in DNA sequencing technologies with the advent of next-generation sequencing (NGS) techniques. NGS methods now allow millions of bases to be sequenced in one round, at a fraction of the cost relative to traditional Sanger sequencing. As costs and capabilities of these technologies continue to improve, we are only beginning to see the possibilities of NGS platforms, which are developing in parallel with online availability of a wide range of biological data sets and scientific publications and allowing us to address a variety of questions not possible before. As techniques and data sets continue to improve and grow, we are rapidly moving to the point where every organism, not just select "model organisms", is open to the power of NGS. This volume presents a brief synopsis of NGS technologies and the development of exemplary applications of such methods in the fields of molecular marker development, hybridization and introgression, transcriptome investigations, phylogenetic and ecological studies, polyploid genetics, and applications for large genebank collections. PMID- 22312117 TI - Targeted enrichment strategies for next-generation plant biology. AB - PREMISE OF THE STUDY: The dramatic advances offered by modern DNA sequencers continue to redefine the limits of what can be accomplished in comparative plant biology. Even with recent achievements, however, plant genomes present obstacles that can make it difficult to execute large-scale population and phylogenetic studies on next-generation sequencing platforms. Factors like large genome size, extensive variation in the proportion of organellar DNA in total DNA, polyploidy, and gene number/redundancy contribute to these challenges, and they demand flexible targeted enrichment strategies to achieve the desired goals. METHODS: In this article, we summarize the many available targeted enrichment strategies that can be used to target partial-to-complete organellar genomes, as well as known and anonymous nuclear targets. These methods fall under four categories: PCR based enrichment, hybridization-based enrichment, restriction enzyme-based enrichment, and enrichment of expressed gene sequences. KEY RESULTS: Examples of plant-specific applications exist for nearly all methods described. While some methods are well established (e.g., transcriptome sequencing), other promising methods are in their infancy (hybridization enrichment). A direct comparison of methods shows that PCR-based enrichment may be a reasonable strategy for accessing small genomic targets (e.g., <=50 kbp), but that hybridization and transcriptome sequencing scale more efficiently if larger targets are desired. CONCLUSIONS: While the benefits of targeted sequencing are greatest in plants with large genomes, nearly all comparative projects can benefit from the improved throughput offered by targeted multiplex DNA sequencing, particularly as the amount of data produced from a single instrument approaches a trillion bases per run. PMID- 22312118 TI - Evolution and radiation in the scorpion Buthus elmoutaouakili Lourenco and Qi 2006 (Scorpiones: Buthidae) at the foothills of the Atlas Mountains (North Africa). AB - When low dispersal ability of an organism meets geographical barriers, the evolution of inter- and intraspecific differentiation is often facilitated. In the Atlas massif of North Africa, the genus Buthus splits into several species and diverges into numerous genetic lineages, often following the orographic structures of mountain systems. Such high mountain ranges often act as barriers for species with reduced mobility even on small spatial scales. To study the effect of orographic structures on organisms with low dispersal ability, we collected 61 individuals of the scorpion species Buthus elmoutaouakili at 18 locations around the southwestern foothills of the High Atlas and Antiatlas and in the Sousse valley (western Morocco). We analyzed intraspecific differentiation patterns within this geographically restricted area of about 100 * 50 km using 452 bp of the cytochrome oxidase I mitochondrial gene. We detected 5 distinct genetic lineages. In a second analysis, we added 61 previously published sequences from Buthus species from Europe and North Africa. Using a molecular clock approach, we detected old splits (4-5 Ma) separating the samples from 1) the western High Atlas and north of these mountains, 2) the Sousse valley and adjoining mountain areas, and 3) the southwestern Antiatlas. Further differentiation happened in the first 2 geographical groups about 3 Ma. Thus, the divergence time estimates based on a Bayesian approach support the onset of differentiation into these main clades along the Pliocene (5-2.3 Ma) when climatic oscillations started and a constant global cooling preceded the glacial interglacial cycles of the Pleistocene. Further genetic splits into parapatric groups are detectable for the Sousse valley main group in the early Pleistocene. The climatic oscillations of the Pliocene and early Pleistocene might have caused repeated range shifts, expansions, and retractions leading to repeated vicariance, hereby producing the hierarchical structure of genetic differentiation in B. elmoutaouakili. A taxonomic revision, including morphological and molecular data, is needed to assess the status of each of these Buthus scorpion lineages. PMID- 22312119 TI - QTL analysis for grain quality traits in 2 BC2F2 populations derived from crosses between Oryza sativa cv Swarna and 2 accessions of O. nivara. AB - The appearance and cooking quality of rice determine its acceptability and price to a large extent. Quantitative trait loci (QTLs) for 12 grain quality traits were mapped in 2 mapping populations derived from Oryza sativa cv Swarna * O. nivara. The BC(2)F(2) population of the cross Swarna * O. nivara IRGC81848 (population 1) was evaluated during 2005 and that from Swarna * O. nivara IRGC81832 (population 2) was evaluated during 2006. Linkage maps were constructed using 100 simple sequence repeat (SSR) markers in population 1 and 75 SSR markers in population 2. In all, 21 QTLs were identified in population 1 (43% from O. nivara) and 37 in population 2 (38% QTLs from O. nivara). The location of O. nivara-derived QTLs mp1.2 for milling percent, kw6.1 for kernel width, and klac12.1 for kernel length after cooking coincided in the 2 populations and appear to be useful for Marker Assisted Selection (MAS). Four QTLs for milling percent, 1 QTL each for amylose content, water uptake, elongation ratio, 2 QTLs for kernel width, and 3 QTLs for gel consistency, each explained more than 20% phenotypic variance. Three QTL clusters for grain quality traits were close to the genes/QTLs for shattering and seed dormancy. QTLs for 4 quality traits were associated with 5 of the 7 major yield QTLs reported in the same 2 mapping populations. Useful introgression lines have been developed for several agronomic traits. It emerges that 40% O. nivara alleles were trait enhancing in both populations, and QTLs for grain quality overlapped with yield meta-QTLs and QTLs for dormancy and seed shattering. PMID- 22312120 TI - Cross-sectional and prospective cohort study of serum 25-hydroxyvitamin D level and obesity in adults: the HUNT study. AB - Experimental studies suggest that vitamin D modulates the activity of adipocytes. The authors examined baseline serum 25-hydroxyvitamin D (25(OH)D) level in relation to prevalent and cumulative incident obesity in Norway. A cohort of 25,616 adults aged 19-55 years participated in both the second and third surveys of the Nord-Trondelag Health Study (HUNT 2 (1995-1997) and HUNT 3 (2006-2008)). Serum 25(OH)D levels measured at baseline and anthropometric measurements taken at both baseline and follow-up were available for a random sample of 2,460 subjects. Overall, 40% of the 2,460 subjects had a serum 25(OH)D level less than 50.0 nmol/L, and 37% had a level of 50.0-74.9 nmol/L. The prevalence and cumulative incidence of obesity, defined as body mass index (weight (kg)/height (m)(2)) >=30, were 12% and 15%, respectively. Lower serum 25(OH)D level was associated with a higher prevalence of obesity. In the 2,165 subjects with baseline BMI less than 30, a serum 25(OH)D level less than 50.0 nmol/L was associated with a significantly increased odds ratio for incident obesity during follow-up (adjusted odds ratio = 1.73, 95% confidence interval: 1.24, 2.41). When prevalent and incident obesity were classified according to waist circumference (>=88 cm for women, >=102 cm for men), similar results were obtained. In addition to prevalent obesity, a serum 25(OH)D level less than 50.0 nmol/L was significantly associated with new-onset obesity in adults. PMID- 22312121 TI - Bony incorporation of soft tissue anterior cruciate ligament grafts in an animal model: autograft versus allograft with low-dose gamma irradiation. AB - BACKGROUND: The effect of low-dose gamma irradiation on healing of soft tissue allografts remains largely unknown. HYPOTHESIS: The authors hypothesized that soft tissue allograft healing to bone would be delayed compared with that of autograft tissue and that low-dose (1.2 Mrad) gamma irradiation would not affect the healing response of allograft tissue after anterior cruciate ligament (ACL) reconstruction. STUDY DESIGN: Controlled laboratory study. METHODS: Forty-eight New Zealand White rabbits underwent bilateral ACL reconstructions with semitendinosus tendon graft. Sixteen rabbits were reconstructed with autografts and the remainder with allografts. The 32 allograft rabbits each received 1 irradiated allograft (1.2 Mrad), with the contralateral leg receiving a nonirradiated allograft. Animals were euthanized at 2 weeks or 8 weeks postoperatively. Tensile stiffness, maximum load, and displacement at maximum load were measured. Tibial and femoral segments were sectioned perpendicular to the tunnel axis allowing for histologic and histomorphometric analyses at the tendon-bone interface. RESULTS: There were no significant differences between the maximum load or stiffness values among all groups at 8 weeks. At 2 weeks, autograft exhibited significantly (P < .01) lower maximum load than did the nonirradiated grafts. Regarding histology, at both 2- and 8-week time points, autograft tendon displayed more advanced degenerative and remodeling processes in comparison with irradiated allograft and nonirradiated allograft. DISCUSSION: The maximum load and stiffness of a healing tendon allograft in ACL reconstruction appear to be unaltered by low-dose (1.2 Mrad) irradiation. At 8 weeks, there were no biomechanical differences in tendon-bone healing of allografts when compared with autograft controls. Histologic analyses suggested a faster remodeling response in autograft specimens in comparison with allografts at both time points. CLINICAL RELEVANCE: The findings support the contention that low-dose gamma irradiation is safe for sterilization of ACL soft tissue allografts without compromise of graft properties at early time points. PMID- 22312122 TI - The emergence level of the musculocutaneous nerve from the brachial plexus: implications for infraclavicular nerve blocks. AB - BACKGROUND: In this cadaveric study we assessed the level of the emergence of the musculocutanous nerve (MCN) relative to needle insertion site during infraclavicular block. METHODS: Forty brachial plexi from 20 embalmed adult cadavers were dissected. The MCN was exposed from its origin on the lateral cord to its penetration into the coracobrachialis muscle. The point of emergence of the MCN from the lateral cord relative to a line drawn directly caudad from the anteromedial tip of the coracoid process was measured. A needle was placed predissection using our previously described technique, and the distance from the needletip to the emergence of the MCN was measured. RESULTS: MCN often emerged distal to the coracoid process. At the needle insertion site, 80% of MCN had already emerged from the lateral cord. The distance of emergence ranged from 8.5 cm proximal to 12 cm distal to the coracoid process. CONCLUSION: This anatomical study suggests that MCN may be one of the factors explaining MCN block failure for the single-injection technique of infraclavicular block using lateral needle trajectory. PMID- 22312123 TI - Brief report: identification of the great auricular nerve by ultrasound imaging and transcutaneous nerve stimulation. AB - Superficial cervical plexus neuropathy after interscalene brachial plexus block affects about 8% of patients postoperatively. One of the nerves involved in superficial cervical plexus neuropathy is the great auricular nerve. We report success in identification of the great auricular nerve with ultrasound and transcutaneous nerve stimulation in a clinical setting in the majority of cases (95% lower confidence limit 63%). Identification of the nerve is significantly more difficult in female and in obese patients. Further studies will allow determination of whether this information will help to reduce the incidence of superficial cervical plexus neuropathy. PMID- 22312124 TI - PT-SAFE: a software tool for development and annunciation of medical audible alarms. AB - BACKGROUND: Recent reports by The Joint Commission as well as the Anesthesia Patient Safety Foundation have indicated that medical audible alarm effectiveness needs to be improved. Several recent studies have explored various approaches to improving the audible alarms, motivating the authors to develop real-time software capable of comparing such alarms. We sought to devise software that would allow for the development of a variety of audible alarm designs that could also integrate into existing operating room equipment configurations. The software is meant to be used as a tool for alarm researchers to quickly evaluate novel alarm designs. METHODS: A software tool was developed for the purpose of creating and annunciating audible alarms. The alarms consisted of annunciators that were mapped to vital sign data received from a patient monitor. An object oriented approach to software design was used to create a tool that is flexible and modular at run-time, can annunciate wave-files from disk, and can be programmed with MATLAB by the user to create custom alarm algorithms. The software was tested in a simulated operating room to measure technical performance and to validate the time-to-annunciation against existing equipment alarms. RESULTS: The software tool showed efficacy in a simulated operating room environment by providing alarm annunciation in response to physiologic and ventilator signals generated by a human patient simulator, on average 6.2 seconds faster than existing equipment alarms. Performance analysis showed that the software was capable of supporting up to 15 audible alarms on a mid-grade laptop computer before audio dropouts occurred. CONCLUSIONS: These results suggest that this software tool provides a foundation for rapidly staging multiple audible alarm sets from the laboratory to a simulation environment for the purpose of evaluating novel alarm designs, thus producing valuable findings for medical audible alarm standardization. PMID- 22312125 TI - TLR4-mediated AKT activation is MyD88/TRIF dependent and critical for induction of oxidative phosphorylation and mitochondrial transcription factor A in murine macrophages. AB - Mitochondria play a critical role in cell survival and death. Mitochondrial recovery during inflammatory processes such as sepsis is associated with cell survival. Recovery of cellular respiration, mitochondrial biogenesis, and function requires coordinated expression of transcription factors encoded by nuclear and mitochondrial genes, including mitochondrial transcription factor A (T-fam) and cytochrome c oxidase (COX, complex IV). LPS elicits strong host defenses in mammals with pronounced inflammatory responses, but also triggers activation of survival pathways such as AKT pathway. AKT/PKB is a serine/threonine protein kinase that plays an important role in cell survival, protein synthesis, and controlled inflammation in response to TLRs. Hence we investigated the role of LPS-mediated AKT activation in mitochondrial bioenergetics and function in cultured murine macrophages (B6-MCL) and bone marrow-derived macrophages. We show that LPS challenge led to increased expression of T-fam and COX subunits I and IV in a time-dependent manner through early phosphorylation of the PI3K/AKT pathway. PI3K/AKT pathway inhibitors abrogated LPS-mediated T-fam and COX induction. Lack of induction was associated with decreased ATP production, increased proinflammatory cytokines (TNF-alpha), NO production, and cell death. The TLR4-mediated AKT activation and mitochondrial biogenesis required activation of adaptor protein MyD88 and Toll/IL-1R domain containing adaptor-inducing IFN-beta. Importantly, using a genetic approach, we show that the AKT1 isoform is pivotal in regulating mitochondrial biogenesis in response to TLR4 agonist. PMID- 22312126 TI - TREM2 and beta-catenin regulate bone homeostasis by controlling the rate of osteoclastogenesis. AB - TREM2 is an immunoreceptor expressed on osteoclasts (OC) and microglia that transmits intracellular signals through the adaptor DAP12. Individuals with genetic mutations inactivating TREM2 or DAP12 develop the Nasu-Hakola disease (NHD) with cystic-like lesions of the bone and brain demyelination that lead to fractures and presenile dementia. The mechanisms of this disease are poorly understood. In this study, we report that TREM2-deficient mice have an osteopenic phenotype reminiscent of NHD. In vitro, lack of TREM2 impairs proliferation and beta-catenin activation in osteoclast precursors (OcP) in response to M-CSF. This defect results in accelerated differentiation of OcP into mature OC. Corroborating the importance of a balanced proliferation and differentiation of OcP for bone homeostasis, we show that conditional deletion of beta-catenin in OcP also results in reduced OcP proliferation and accelerated osteoclastogenesis in vitro as well as osteopenia in vivo. These results reveal that TREM2 regulates the rate of osteoclastogenesis and provide a mechanism for the bone pathology in NHD. PMID- 22312127 TI - Three novel acetylation sites in the Foxp3 transcription factor regulate the suppressive activity of regulatory T cells. AB - The Foxp3 transcription factor is the master regulator of regulatory T cell (Treg) differentiation and function. Its activity is regulated by reversible acetylation. Using mass spectrometry of immunoprecipitated proteins, we identify three novel acetylation sites in murine Foxp3 (K31, K262, and K267) and the corresponding sites in human FOXP3 proteins. Newly raised modification-specific Abs against acetylated K31 and K267 confirm acetylation of these residues in murine Tregs. Mutant Foxp3 proteins carrying arginine substitutions at the three acetylation sites (3KR) accumulate in T cells to higher levels than wild-type Foxp3 and exert better suppressive activity in coculture experiments. Acetylation and stability of wild-type, but not mutant, Foxp3 is enhanced when cells are treated with Ex-527, an inhibitor of the NAD(+)-dependent deacetylase SIRT1. Treatment with Ex-527 promotes Foxp3 expression during induced Treg differentiation, enhances Foxp3 levels in natural Tregs, and prevents loss of Foxp3 expression in adoptively transferred Tregs in mice. Our data identify SIRT1 as a negative regulator of Treg function via deacetylation of three novel target sites in Foxp3. SIRT1 inhibitors strengthen the suppressive activity of Tregs and may be useful in enhancing Treg-based therapeutic approaches to autoimmune diseases or graft rejections. PMID- 22312128 TI - Cellular and molecular requirements for rejection of B16 melanoma in the setting of regulatory T cell depletion and homeostatic proliferation. AB - We have recently demonstrated that adoptive transfer of regulatory T cell depleted polyclonal T cells into lymphopenic mice leads to rejection of B16 melanoma, which generated an opportunity to study host requirements for tumor rejection when it effectively occurred. CD8(+) T cell priming and tumor rejection required tumor Ag cross-presentation, as evidenced by tumor outgrowth in Kb(-/-) bone marrow chimeric or B71/2(-/-) mice. CD4(+) T cells were additionally required for optimal tumor control, although not through classical CD4 "help," as the frequency of primed CD8(+) T cells was similar in the absence of CD4(+) T cells, and tumor rejection did not depend upon CD40-CD40L interactions or on IL-2 production by CD4(+) T cells. Rather, CD4(+) T cells appeared to act at the effector phase of tumor rejection and responded to B16-derived Ags in vitro. At the effector phase, IFN-gamma production by transferred T cells, but not host cells, was necessary. IFN-gamma acted either on host or tumor cells and was associated with reduced tumor vascularity. Finally, tumor rejection occurred after transfer of TNF-alpha, perforin, or FasL-deficient T cells. However, perforin/FasL double-knockout T cells failed to reject, arguing that the killing of B16 melanoma cells could occur either via the cytotoxic granule or Fas pathways. Collectively, these results support a model in which host tumor Ag cross-presentation primes adoptively transferred T cells, which remain functional in the setting of homeostatic proliferation and regulatory T cell depletion, and which promote tumor rejection via IFN-gamma and lysis via cytotoxic granules and/or FasL. PMID- 22312129 TI - Spatiotemporal inhibition of innate immunity signaling by the Tbc1d23 RAB-GAP. AB - We previously identified Tbc1d23 as a candidate novel regulator of innate immunity using comparative genomics RNA interference screens in Caenorhabditis elegans and mouse macrophages. Using Tbc1d23 knockout mice and macrophages engineered to overexpress Tbc1d23, we now show that Tbc1d23 is a general inhibitor of innate immunity signaling, strongly inhibiting multiple TLR and dectin-signaling pathways. Tbc1d23 likely acts downstream of the TLR-signaling adaptors MyD88 and Trif and upstream of the transcription factor XBP1. Importantly, like XBP1, Tbc1d23 affects the maintenance, but not the initiation, of inflammatory cytokine production induced by LPS. Tbc1d23 acts as a RAB-GAP to regulate innate immunity signaling. Thus, Tbc1d23 exerts its inhibitory effect on innate immunity signaling in a spatiotemporal fashion. The identification of a novel spatiotemporal regulator of innate immunity signaling validates the comparative genomics approach for innate immunity gene discovery. PMID- 22312130 TI - Selective dependence of H2-M3-restricted CD8 responses on IL-15. AB - We studied whether CD8 T cell responses that are mediated by unconventional MHC class Ib molecules are IL-15 dependent in mice. CD8(+) T cell responses to Listeria monocytogenes infection that are restricted by the MHC class Ib molecule H2-M3 decreased in the absence of IL-15, whereas other primary MHC class Ib- and MHC class Ia-restricted responses were IL-15 independent. This result was confirmed in MHC class Ia-deficient mice in which IL-15 deficiency also reduced H2-M3-restricted but not all CD8 T cell responses to L. monocytogenes. IL-15 deficiency did not affect proliferation or survival of responding H2-M3 restricted CD8(+) T cells, but IL-15 was necessary to detect H2-M3-restricted CD8(+) T cells in naive mice. This finding suggests that these CD8(+) T cells require IL-15 during development, but become IL-15 independent after activation. IL-15 was necessary for the survival of most class Ib-restricted CD8(+) T cells, starting at the mature thymocyte stage in naive mice, but does not affect a distinct CD44(low)/CD122(low) subpopulation. These data suggest that the nature of the selecting MHC class Ib molecule determines whether CD8(+) T cells acquire IL-15 dependence during thymic development. PMID- 22312131 TI - Estimating equations for glomerular filtration rate in the era of creatinine standardization: a systematic review. AB - BACKGROUND: Clinical laboratories are increasingly reporting estimated glomerular filtration rate (GFR) by using serum creatinine assays traceable to a standard reference material. PURPOSE: To review the performance of GFR estimating equations to inform the selection of a single equation by laboratories and the interpretation of estimated GFR by clinicians. DATA SOURCES: A systematic search of MEDLINE, without language restriction, between 1999 and 21 October 2011. STUDY SELECTION: Cross-sectional studies in adults that compared the performance of 2 or more creatinine-based GFR estimating equations with a reference GFR measurement. Eligible equations were derived or reexpressed and validated by using creatinine measurements traceable to the standard reference material. DATA EXTRACTION: Reviewers extracted data on study population characteristics, measured GFR, creatinine assay, and equation performance. DATA SYNTHESIS: Eligible studies compared the MDRD (Modification of Diet in Renal Disease) Study and CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations or modifications thereof. In 12 studies in North America, Europe, and Australia, the CKD-EPI equation performed better at higher GFRs (approximately >60 mL/min per 1.73 m(2)) and the MDRD Study equation performed better at lower GFRs. In 5 of 8 studies in Asia and Africa, the equations were modified to improve their performance by adding a coefficient derived in the local population or removing a coefficient. LIMITATION: Methods of GFR measurement and study populations were heterogeneous. CONCLUSION: Neither the CKD-EPI nor the MDRD Study equation is optimal for all populations and GFR ranges. Using a single equation for reporting requires a tradeoff to optimize performance at either higher or lower GFR ranges. A general practice and public health perspective favors the CKD-EPI equation. PRIMARY FUNDING SOURCE: Kidney Disease: Improving Global Outcomes. PMID- 22312132 TI - Urocortin-dependent effects on adrenal morphology, growth, and expression of steroidogenic enzymes in vivo. AB - Urocortin (UCN) 1, 2, and 3 are members of the corticotropin-releasing factor (CRF) family that display varying affinities to the CRF receptor 1 (CRFR1 (CRHR1)) and 2 (CRFR2 (CRHR2)). UCNs represent important modulators of stress responses and are involved in the control of anxiety and related disorders. In addition to the CNS, UCNs and CRFRs are highly expressed in several tissues including the adrenal gland, indicating the presence of UCN-dependent regulatory mechanisms in these peripheral organ systems. Using knockout (KO) mouse models lacking single or multiple Ucn genes, we examined the potential role of the three different Ucns on morphology and function of the adrenal gland. Adrenal morphology was investigated, organ size, cell size, and number were quantified, and growth kinetics were studied by proliferative cell nuclear antigen staining and Ccnd1 expression analysis. Furthermore, mRNA expression of enzymes involved in steroidogenesis and catecholamine synthesis was quantified by real-time PCR. Following this approach, Ucn2, Ucn1/Ucn2 dKO and Ucn1/Ucn2/Ucn3 tKO animals showed a significant cellular hypotrophy of the adrenal cortex and an increase in Ccnd1 expression, whereas in all other genotypes, no changes were observable in comparison to age-matched controls. For steroidogenesis, Ucn2/Ucn3 dKO animals displayed the most pronounced changes, with significant increases in all investigated enzymes, providing indirect evidence for increased stress behavior. Taken together, these data suggest that mainly Ucn2 and Ucn3 could be involved in adrenal stress response regulation while Ucn2 additionally appears to play a role in morphology and growth of the adrenal gland. PMID- 22312133 TI - Associations between obesity and cancer: the role of fatty acid synthase. PMID- 22312135 TI - Body mass index and risk of colorectal cancer according to fatty acid synthase expression in the nurses' health study. AB - Fatty acid synthase (FASN) plays an important role in energy metabolism of fatty acids and is overexpressed in some colon cancers. We investigated whether associations between body mass index (BMI) and risk of colorectal cancer varied according to FASN expression. During follow-up of 109,051 women in the ongoing prospective Nurses' Health Study, a total of 1351 incident colon and rectal cancers were diagnosed between 1986 and 2004. We constructed tissue microarrays of the available resected tumor samples (n = 536), and FASN expression was analyzed by immunohistochemistry. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. All statistical tests were two-sided. High BMI was associated with an increased risk of FASN-negative (no or weak expression) colorectal cancer compared with normal BMI (high BMI [>= 30 kg/m(2)], ie, obese vs normal BMI [18.5-22.9 kg/m(2)], HR = 2.25, 95% CI = 1.49 to 3.40, P(trend) < .001) but not with FASN positive (moderate to strong expression) colorectal cancer. A statistically significant heterogeneity in colorectal cancer risks was observed between FASN negative and FASN-positive tumors (P(heterogeneity) = .033). The age-adjusted incidence rates for FASN-positive and FASN-negative colorectal cancers were 10.9 and 7.1, respectively, per 100,000 person-years. This molecular pathological epidemiology study supports a role of energy metabolism in colorectal cancer pathogenesis. PMID- 22312136 TI - Brain and whole-body imaging of nociceptin/orphanin FQ peptide receptor in humans using the PET ligand 11C-NOP-1A. AB - Nociceptin/orphanin FQ peptide (NOP) receptor is a new class of opioid receptor that may play a pathophysiologic role in anxiety and drug abuse and is a potential therapeutic target in these disorders. We previously developed a high affinity PET ligand, (11)C-NOP-1A, which yielded promising results in monkey brain. Here, we assessed the ability of (11)C-NOP-1A to quantify NOP receptors in human brain and estimated its radiation safety profile. METHODS: After intravenous injection of (11)C-NOP-1A, 7 healthy subjects underwent brain PET for 2 h and serial sampling of radial arterial blood to measure parent radioligand concentrations. Distribution volume (V(T); a measure of receptor density) was determined by compartmental (1- and 2-tissue) and noncompartmental (Logan analysis and Ichise's bilinear analysis [MA1]) methods. A separate group of 9 healthy subjects underwent whole-body PET to estimate whole-body radiation exposure (effective dose). RESULTS: After (11)C-NOP-1A injection, the peak concentration of radioactivity in brain was high (~5-7 standardized uptake values), occurred early (~10 min), and then washed out quickly. The unconstrained 2-tissue-compartment model gave excellent V(T) identifiability (~1.1% SE) and fitted the data better than a 1-tissue-compartment model. Regional V(T) values (mL.cm(-3)) ranged from 10.1 in temporal cortex to 5.6 in cerebellum. V(T) was well identified in the initial 70 min of imaging and remained stable for the remaining 50 min, suggesting that brain radioactivity was most likely parent radioligand, as supported by the fact that all plasma radiometabolites of (11)C NOP-1A were less lipophilic than the parent radioligand. Voxel-based MA1 V(T) values correlated well with results from the 2-tissue-compartment model, showing that parametric methods can be used to compare populations. Whole-body scans showed radioactivity in brain and in peripheral organs expressing NOP receptors, such as heart, pancreas, and spleen. (11)C-NOP-1A was significantly metabolized and excreted via the hepatobiliary route. Gallbladder had the highest radiation exposure (21 MUSv/MBq), and the effective dose was 4.3 MUSv/MBq. CONCLUSION: (11)C-NOP-1A is a promising radioligand that reliably quantifies NOP receptors in human brain. The effective dose in humans is low and similar to that of other (11)C-labeled radioligands, allowing multiple scans in 1 subject. PMID- 22312134 TI - Second malignant neoplasms and cardiovascular disease following radiotherapy. AB - Second malignant neoplasms (SMNs) and cardiovascular disease (CVD) are among the most serious and life-threatening late adverse effects experienced by the growing number of cancer survivors worldwide and are due in part to radiotherapy. The National Council on Radiation Protection and Measurements (NCRP) convened an expert scientific committee to critically and comprehensively review associations between radiotherapy and SMNs and CVD, taking into account radiobiology; genomics; treatment (ie, radiotherapy with or without chemotherapy and other therapies); type of radiation; and quantitative considerations (ie, dose-response relationships). Major conclusions of the NCRP include: 1) the relevance of older technologies for current risk assessment when organ-specific absorbed dose and the appropriate relative biological effectiveness are taken into account and 2) the identification of critical research needs with regard to newer radiation modalities, dose-response relationships, and genetic susceptibility. Recommendation for research priorities and infrastructural requirements include 1) long-term large-scale follow-up of extant cancer survivors and prospectively treated patients to characterize risks of SMNs and CVD in terms of radiation dose and type; 2) biological sample collection to integrate epidemiological studies with molecular and genetic evaluations; 3) investigation of interactions between radiotherapy and other potential confounding factors, such as age, sex, race, tobacco and alcohol use, dietary intake, energy balance, and other cofactors, as well as genetic susceptibility; 4) focusing on adolescent and young adult cancer survivors, given the sparse research in this population; and 5) construction of comprehensive risk prediction models for SMNs and CVD to permit the development of follow-up guidelines and prevention and intervention strategies. PMID- 22312137 TI - Effects of school closure on incidence of pandemic influenza in Alberta, Canada. AB - BACKGROUND: Control of pandemic influenza by social-distancing measures, such as school closures, is a controversial aspect of pandemic planning. However, investigations of the extent to which these measures actually affect the progression of a pandemic have been limited. OBJECTIVE: To examine correlations between the incidence of pandemic H1N1 (pH1N1) influenza in Alberta, Canada, in 2009 and school closures or weather changes, and to estimate the effects of school closures and weather changes on pH1N1 transmission. DESIGN: Mathematical transmission models were fit to data that compared the pattern of confirmed pH1N1 cases with the school calendar and weather patterns. SETTING: Alberta, Canada, from 19 April 2009 to 2 January 2010. DATA SOURCES: 2009 virologic test results, 2006 census data, 2009 daily temperature and humidity data, and 2009 school calendars. MEASUREMENTS: Age-specific daily counts of positive results for pH1N1 from the complete database of 35 510 specimens submitted to the Alberta Provincial Laboratory for Public Health for virologic testing from 19 April 2009 to 2 January 2010. RESULTS: The ending and restarting of school terms had a major effect in attenuating the first wave and starting the second wave of pandemic influenza cases. Mathematical models suggested that school closure reduced transmission among school-age children by more than 50% and that this was a key factor in interrupting transmission. The models also indicated that seasonal changes in weather had a significant effect on the temporal pattern of the epidemic. LIMITATIONS: Data probably represent a small sample of all viral infections. The mathematical models make simplifying assumptions in order to make simulations and analysis feasible. CONCLUSION: Analysis of data from unrestricted virologic testing during an influenza pandemic provides compelling evidence that closing schools can have dramatic effects on transmission of pandemic influenza. School closure seems to be an effective strategy for slowing the spread of pandemic influenza in countries with social contact networks similar to those in Canada. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, and Public Health Agency of Canada. PMID- 22312138 TI - Vignette-based study of ovarian cancer screening: do U.S. physicians report adhering to evidence-based recommendations? AB - BACKGROUND: No professional society or group recommends routine ovarian cancer screening, yet physicians' enthusiasm for several cancer screening tests before benefit has been proven suggests that some women may be exposed to potential harms. OBJECTIVE: To provide nationally representative estimates of physicians' reported nonadherence to recommendations against ovarian cancer screening. DESIGN: Cross-sectional survey of physicians offering women's primary care. The 12-page questionnaire contained a woman's annual examination vignette and questions about offers or orders for transvaginal ultrasonography (TVU) and cancer antigen 125 (CA-125). SETTING: United States. PARTICIPANTS: 3200 physicians randomly sampled equally from the 2008 American Medical Association Physician Masterfile lists of family physicians, general internists, and obstetrician-gynecologists; 61.7% responded. After exclusions, 1088 respondents were included; their responses were weighted to represent the specialty distribution of practicing U.S. physicians nationally. MEASUREMENTS: Reported nonadherence to screening recommendations (defined as sometimes or almost always ordering screening TVU or CA-125 or both). RESULTS: Twenty-eight percent (95% CI, 24.5% to 32.9%) of physicians reported nonadherence to screening recommendations for women at low risk for ovarian cancer; 65.4% (CI, 61.1% to 69.4%) did so for women at medium risk for ovarian cancer. Six percent (CI, 4.4% to 8.9%) reported routinely ordering or offering ovarian cancer screening for low-risk women, as did 24.0% (CI, 20.5% to 28.0%) for medium-risk women (P <= 0.001). Thirty-three percent believed TVU or CA-125 was an effective screening test. In adjusted analysis, actual and physician-perceived patient risk, patient request for ovarian cancer screening, and physician belief that TVU or CA-125 was an effective screening test were the strongest predictors of physician-reported nonadherence to published recommendations. LIMITATION: The results are limited by their reliance on survey methods; there may be respondent-nonrespondent bias. CONCLUSION: One in 3 physicians believed that ovarian cancer screening was effective, despite evidence to the contrary. Substantial proportions of physicians reported routinely offering or ordering ovarian cancer screening, thereby exposing women to the documented risks of these tests. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention and the National Cancer Institute. PMID- 22312139 TI - Sex differences in implantable cardioverter-defibrillator outcomes: findings from a prospective defibrillator database. AB - BACKGROUND: Sex differences in the use and outcomes of implantable cardioverter defibrillators (ICDs) have not been fully studied. OBJECTIVE: To examine potential sex differences in ICD implantation and device outcomes. DESIGN: Health payer-mandated, prospective study of patients referred for ICD implantation, with comprehensive, longitudinal follow-up for complications, deaths, and device outcomes. SETTING: 18 ICD implantation and follow-up centers in Ontario, Canada. PATIENTS: 6021 patients (4733 men) referred for ICD implantation from February 2007 to July 2010. MEASUREMENTS: Multivariate-adjusted ICD implantation rate, complications up to day 45, multivariate-adjusted complications, device outcomes (including appropriate shocks and therapies), and deaths occurring during 1-year follow-up. RESULTS: Rates of ICD implantation were similar in men and women (relative risk, 0.99 [95% CI, 0.97 to 1.02]; P = 0.60). However, women were significantly more likely to experience major complications by 45 days (odds ratio, 1.78 [CI, 1.24 to 2.58]; P = 0.002) and 1 year (hazard ratio [HR], 1.91 [CI, 1.48 to 2.47]; P < 0.001) after implantation. Occurrence of any major or minor complication was also increased in women at both 45-day follow-up (odds ratio, 1.50 [CI, 1.12 to 2.00]; P = 0.006) and 1-year follow-up (HR, 1.55 [CI, 1.25 to 1.93]; P < 0.001). After implantation, women were less likely than men to receive appropriate ICD shock (HR, 0.69 [CI, 0.51 to 0.93]; P = 0.015) or appropriate therapy via shock or antitachycardia pacing (HR, 0.73 [CI, 0.59 to 0.90]; P = 0.003). Total mortality among defibrillator recipients did not differ between men and women (HR, 1.00 [CI, 0.64 to 1.55]; P = 0.99). LIMITATION: The differential effects of sex on prereferral events were not examined. CONCLUSION: Although ICD implantation rates were similar after referral to an electrophysiologist, women who underwent ICD implantation had greater risks for complications and were less likely to experience appropriate ICD-delivered therapies than men. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research and Ontario Ministry of Health and Long-Term Care. PMID- 22312140 TI - End-of-life care discussions among patients with advanced cancer: a cohort study. AB - BACKGROUND: National guidelines recommend that physicians discuss end-of-life (EOL) care planning with patients with cancer whose life expectancy is less than 1 year. OBJECTIVE: To evaluate the incidence of EOL care discussions for patients with stage IV lung or colorectal cancer and where, when, and with whom these discussions take place. DESIGN: Prospective cohort study of patients diagnosed with lung or colorectal cancer from 2003 to 2005. SETTING: Participants lived in Northern California, Los Angeles County, North Carolina, Iowa, or Alabama or received care in 1 of 5 large HMOs or 1 of 15 Veterans Health Administration sites. PATIENTS: 2155 patients with stage IV lung or colorectal cancer. MEASUREMENTS: End-of-life care discussions reported in patient and surrogate interviews or documented in medical records through 15 months after diagnosis. RESULTS: 73% of patients had EOL care discussions identified by at least 1 source. Among the 1470 patients who died during follow-up, 87% had EOL care discussions, compared with 41% of the 685 patients who were alive at the end of follow-up. Of the 1081 first EOL care discussions documented in records, 55% occurred in the hospital. Oncologists documented EOL care discussions with only 27% of their patients. Among 959 patients with documented EOL care discussions who died during follow-up, discussions took place a median of 33 days before death. LIMITATIONS: The depth and quality of EOL care discussions was not evaluated. Much of the information about discussions came from surrogates of patients who died before baseline interviews could be obtained. CONCLUSION: Although most patients with stage IV lung or colorectal cancer discuss EOL care planning with physicians before death, many discussions occur during acute hospital care, with providers other than oncologists, and late in the course of illness. PRIMARY FUNDING SOURCE: National Cancer Institute and Department of Veterans Affairs. PMID- 22312141 TI - Oral pharmacologic treatment of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians. AB - DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the comparative effectiveness and safety of type 2 diabetes medications. METHODS: This guideline is based on a systematic evidence review evaluating literature published on this topic from 1966 through April 2010 that was identified by using MEDLINE (updated through December 2010), EMBASE, and the Cochrane Central Register of Controlled Trials. Searches were limited to English-language publications. The clinical outcomes evaluated for this guideline included all-cause mortality, cardiovascular morbidity and mortality, cerebrovascular morbidity, neuropathy, nephropathy, and retinopathy. This guideline grades the evidence and recommendations by using the American College of Physicians clinical practice guidelines grading system. RECOMMENDATION 1: ACP recommends that clinicians add oral pharmacologic therapy in patients diagnosed with type 2 diabetes when lifestyle modifications, including diet, exercise, and weight loss, have failed to adequately improve hyperglycemia (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 2: ACP recommends that clinicians prescribe monotherapy with metformin for initial pharmacologic therapy to treat most patients with type 2 diabetes (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 3: ACP recommends that clinicians add a second agent to metformin to treat patients with persistent hyperglycemia when lifestyle modifications and monotherapy with metformin fail to control hyperglycemia (Grade: strong recommendation; high-quality evidence). PMID- 22312142 TI - Launching complex medical workups from an urgent care platform. AB - The basic parameters for medical workups have scarcely changed in the past 30 years. That is, what the internal medicine community has deemed acceptable for outpatient, inpatient, emergency department, and urgent care evaluation has remained pretty much stable or stagnant during all that time. We are failing to take advantage of the phenomenal speed and accuracy of new laboratory and imaging technologies. Due to Hurricane Katrina, which destroyed the Veterans Administration Hospital in New Orleans, those of us who work in its urgent care clinic were forced to undertake complex medical workups from an 8-to-5, walk-in platform. We have been amazed at the efficiency of this. Workups that used to take weeks can often be done in a few hours or days. What we have discovered here serendipitously may be worth deliberately duplicating elsewhere. PMID- 22312143 TI - Lifelong curiosity: Frederick Novy and the rat virus. AB - Frederick Novy (1864-1957) was a U.S. physician, medical researcher, and influential microbiologist of the early 20th century who devised culture techniques to visualize anaerobic bacteria, parasites, and spirochetes. In 1909 he began to investigate the cause of unexplained deaths in his laboratory rats, which he hypothesized were due to an "ultramicroscopic organism" or "filterable virus." But in 1918, the test tubes he had been using for these experiments vanished from his laboratory. His dream of finding a virus as the likely cause of the mysterious deaths of his rats apparently was lost. Novy retired in 1935. Thirty-three years later, in 1951, a box containing the test tubes was discovered by chance during clean-up in preparation for a laboratory move. Novy's curiosity had not waned with time. Notified of the find, and 16 years into his retirement, he returned to his laboratory at the age of 88 to continue the experiments that he had begun more than 40 years earlier. He completed his investigations in 1953 and published his findings that a virus was indeed the unidentified organism that had swiftly killed his laboratory rats in 1909. PMID- 22312144 TI - Getting schooled: school closure, age distribution, and pandemic mitigation. PMID- 22312145 TI - Is biology destiny or can we optimize care for all patients? PMID- 22312146 TI - A case of racism and reconciliation. PMID- 22312147 TI - Effectiveness of primary care-relevant treatments for obesity in adults. PMID- 22312148 TI - Effectiveness of primary care-relevant treatments for obesity in adults. PMID- 22312149 TI - Comparative effectiveness of digital versus film-screen mammography. PMID- 22312150 TI - Comparative effectiveness of digital versus film-screen mammography. PMID- 22312151 TI - Comparative effectiveness of digital versus film-screen mammography. PMID- 22312152 TI - Reducing 30-day rehospitalization. PMID- 22312153 TI - Reducing 30-day rehospitalization. PMID- 22312154 TI - Summaries for patients: Effects of school closure on incidence of pandemic influenza in Alberta, Canada. PMID- 22312155 TI - Summaries for patients: Implantable cardioverter-defibrillators in women. PMID- 22312156 TI - Summaries for patients: End-of-life care discussions between patients with advanced cancer and doctors. PMID- 22312157 TI - Summaries for patients: Oral drug treatment of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians. PMID- 22312158 TI - In the clinic. Palliative care. PMID- 22312159 TI - The Dutch Childhood Oncology Group guideline for follow-up of asymptomatic cardiac dysfunction in childhood cancer survivors. AB - BACKGROUND: The Late Effects of Childhood Cancer task force of the Dutch Childhood Oncology Group (DCOG LATER) developed a guideline for follow-up of asymptomatic cardiac dysfunction in childhood cancer survivors (CCS). In this paper, we present the methods, available evidence and final recommendations of our guideline. MATERIALS AND METHODS: A multidisciplinary working group specified clinical questions that should be answered to get to recommendations for the guideline. We carried out short or extensive evidence summaries and determined methodological quality of studies and levels of evidence in order to answer all clinical questions. When evidence was lacking for CCS, we carefully extrapolated evidence from other populations. Final recommendations were based on evidence and consensus. RESULTS: There was high-level evidence for the increased risk of cardiac dysfunction in CCS and its main risk factors. Evidence was lacking regarding the prognosis, diagnosis and treatment of cardiac dysfunction in CCS. We recommended echocardiographic screening for asymptomatic cardiac dysfunction in CCS treated with cardiotoxic treatments and counseling about potential advantages and disadvantages of our screening recommendations. CONCLUSION: The DCOG LATER guideline recommends risk-based screening for asymptomatic cardiac dysfunction in CCS, but it should be noted that recommendations are not completely supported by evidence in CCS. PMID- 22312160 TI - Association between the IL-1 family gene cluster and spondyloarthritis. AB - OBJECTIVE: Spondyloarthritis is a group of articular disorders sharing a genetic background. Polymorphisms in the IL-1 gene cluster have previously been associated with ankylosing spondylitis (AS), a subset of spondyloarthritis. This study examined the association between several of these polymorphisms and the whole spondyloarthritis. Particular attention was devoted to genotype-phenotype correlations. METHODS: Seven single-nucleotide polymorphisms (SNP) and a variable number tandem repeat located in the IL-1 gene cluster were genotyped in 185 independent spondyloarthritis trios. Family-based association test (FBAT) was computed using the FBAT software. Analysis was carried in spondyloarthritis as a whole and also in AS. A case-control replication study was performed for four of the SNP, in an independent sample of 414 spondyloarthritis and 264 controls. A combined analysis of both studies was performed. RESULTS: The SNP rs2856836 in IL1A was significantly associated with spondyloarthritis (p=0.009) and AS (p=0.010) in the family study. The case-control study revealed an association between another IL1A variant (rs1894399) and AS (p=0.035), and between IL1F10.3 (rs3811058) and spondyloarthritis (p=0.041). By combining family and case-control studies an association between AS and IL1A was confirmed (rs1894399, p=0.024), whereas non-AS was more significantly associated with IL1F10.3 (p=0.0043). Family based and case-control studies revealed significant association between the two most frequent haplotypes combining the four SNP of the replication study and both spondyloarthritis (p=0.0054 and p=0.038) and AS phenotypes (p=0.018 and 0.0036). CONCLUSION: This study is the first to demonstrate an association between several polymorphisms located in the IL-1 gene cluster and spondyloarthritis as a whole. The IL1A locus was strongly associated with AS phenotype, whereas IL1F10 was associated with non-AS. PMID- 22312161 TI - Increased interleukin (IL)-7Ralpha expression in salivary glands of patients with primary Sjogren's syndrome is restricted to T cells and correlates with IL-7 expression, lymphocyte numbers and activity. AB - OBJECTIVE: To identify interleukin (IL)-7Ralpha expression in the labial salivary gland (LSG) of patients with primary Sjogren's syndrome (pSS) and non-Sjogren's syndrome sicca (nSS-sicca) and to study its correlation with glandular inflammation and IL-7 expression. METHODS: The presence of infiltrating immune cells and IL-7Ralpha cells in inflamed LSG of patients with pSS (n=12) and nSS sicca controls (n=7) was studied by immunohistochemistry and fluorescence activated cell sorting analysis upon tissue digestion (n=15 and n=13, respectively). Additionally, the correlations of IL-7Ralpha cells with hallmark disease parameters of pSS, major infiltrating inflammatory cells and IL-7 were assessed. RESULTS: In the LSG of patients with pSS increased numbers of IL 7Ralpha cells were found as compared with nSS-sicca patients. IL7Ralpha cells strongly correlated with the lymphocytic focus score, IL-7 expression, the decrease in percentage of IgA plasma cells and numbers of CD3 T cells, CD20 B cells, and CD1a and CD208 myeloid dendritic cells. Analysis of isolated cells from the LSG demonstrated strongly increased percentages of IL-7Ralpha CD3 T cells in pSS as compared with nSS, showing abundant IL-7Ralpha expression on both CD4 and CD8 T cells. Other CD45 leucocytes and CD45- tissue cells scarcely expressed IL-7Ralpha. Percentages of IL-7Ralpha T cells also significantly correlated with glandular inflammation. CONCLUSIONS: This study shows the presence of increased IL-7Ralpha T cells in the LSG of patients with pSS and their association with the severity of sialadenitis, disease parameters and IL-7 expression. Considering the immunostimulatory ability of IL-7Ralpha T cells and IL-7, this suggests that IL-7(R)-dependent T cell-driven immune activation plays an important role in inflammation in pSS. PMID- 22312162 TI - Restricted diffusion in vanishing white matter. AB - OBJECTIVE: To investigate the occurrence of restricted diffusion in vanishing white matter, the affected structures,the time of occurrence in the disease course, and the histopathologic correlate. DESIGN: Retrospective observational study. PATIENTS: Forty-six patients with vanishing white matter. SETTING: VU University Medical Center. MAIN OUTCOME MEASURES: We evaluated all available diffusion-weighted imaging studies in our database and recorded the areas that displayed restricted diffusion in 1 or more patients. We measured the mean apparent diffusion coefficients of these areas in all patients and used the putamen for internal quality control. We recorded age and disease duration during magnetic resonance imaging, and we obtained a magnetic resonance image of a postmortem vanishing white matter brain slice and subsequently performed histopathologic stainings. RESULTS: Areas with decreased apparent diffusion coefficient values were found in the U fibers (n=21 patients), cerebellar white matter (n=18), middle cerebellar peduncle(n=8), pyramids (n=8), genu (n=8) or splenium (n=9) of the corpus callosum, and posterior limb of the internal capsule(n=10). Overall, patients showing restricted diffusion(n=32)were younger and had shorter disease duration. Histopathologic analysis of the brain slice revealed that regions with restricted diffusion had a higher cell density. CONCLUSION: In vanishing white matter, restricted diffusion can be found in relatively spared regions with high cellularity particularly in young patients with short disease duration. PMID- 22312163 TI - Revised criteria for mild cognitive impairment may compromise the diagnosis of Alzheimer disease dementia. AB - OBJECTIVE: To evaluate the potential impact of revised criteria for mild cognitive impairment (MCI), developed by a work group sponsored by the National Institute on Aging and the Alzheimer's Association, on the diagnosis of very mild and mild Alzheimer disease (AD)dementia. DESIGN: Retrospective review of ratings of functional impairment across diagnostic categories. SETTING: Alzheimer's Disease Centers and the National Alzheimer's Coordinating Center. PARTICIPANTS: Individuals (N=17 535) with normal cognition,MCI, or AD dementia. MAIN OUTCOME MEASURES: The functional ratings of individuals with normal cognition, MCI, or AD dementia who were evaluated at Alzheimer's Disease Centers and submitted to the National Alzheimer's Coordinating Center were assessed in accordance with the definition of "functional independence" allowed by the revised criteria. Pairwise demographic differences between the 3 diagnostic groups were tested using t tests for continuous variables and 2 for categorical variables. RESULTS: Almost all (99.8%) individuals currently diagnosed with very mild AD dementia and the large majority(92.7%) of those diagnosed with mild AD dementia could be reclassified as having MCI with the revised criteria,based on their level of impairment in the Clinical Dementia Rating domains for performance of instrumental activities of daily living in the community and at home.Large percentages of these individuals with AD dementia also meet the revised "functional independence" criterion for MCI as measured by the Functional Assessment Questionnaire. CONCLUSIONS: The categorical distinction between MCI and milder stages of AD dementia has been compromised by the revised criteria. The resulting diagnostic overlap supports the premise that "MCI due to AD" represents the earliest symptomatic stage of AD. PMID- 22312164 TI - Adult-onset vanishing white matter disease due to a novel EIF2B3 mutation. AB - OBJECTIVE: To report a novel mutation in the gene EIF2B3 responsible for a late onset form of vanishing white matter disease. DESIGN: Case report. SETTING: University teaching hospital. PATIENT: A 29-year-old pregnant woman with a history of premature ovarian failure and hemiplegic migraines presented with a 10 week history of progressive confusion and headaches. Magnetic resonance imaging of the brain revealed a diffuse leukoencephalopathy. RESULTS: Sequencing of the exons and intron boundaries of EIF2B3 uncovered 2 missense mutations: c.260C>T(p.Ala87Val) and c.272G>A(p.Arg91His). To our knowledge,the latter missense mutation has never been previously reported. CONCLUSION: This is the second report of adult-onset vanishing white matter disease due to mutations in EIF2B3 and the first report of the c.272G>A (p.Arg91His) missense mutation. PMID- 22312165 TI - Novel infantile-onset leukoencephalopathy with high lactate level and slow improvement. AB - OBJECTIVE: To describe a novel pattern of magnetic resonance imaging (MRI) abnormalities as well as the associated clinical and laboratory findings. DESIGN: The MRIs of more than 3000 patients with an unclassified leukoencephalopathy were systematically reviewed.Clinical and laboratory data were retrospectively collected. SETTING: University hospital. PATIENTS: Seven patients (3 male) shared similar MRI abnormalities and clinical features. MAIN OUTCOME MEASURES: Pattern of MRI abnormalities and clinical and laboratory findings. RESULTS: The MRIs showed signal abnormalities of the deep cerebral white matter, corpus callosum, thalamus, basal ganglia,brainstem, and cerebellar white matter between the ages of 9 months and 2 years. On follow-up, abnormalities gradually improved. Clinical regression occurred in the second half-year of life with spasticity and loss of milestones.From the second year on, clinical improvement occurred.So far, no second episode of regression has happened.Lactate levels were elevated during clinical regression. CONCLUSION: These patients represent a single novel leukoencephalopathy,probably caused by a mitochondrial defect. PMID- 22312166 TI - Hypothermia for neonatal hypoxic ischemic encephalopathy: an updated systematic review and meta-analysis. AB - OBJECTIVE: To establish the evidence of therapeutic hypothermia for newborns with hypoxic ischemic encephalopathy(HIE). DATA SOURCES: Cochrane Central Register of Controlled Trials, Oxford Database of Perinatal Trials, MEDLINE, EMBASE, and previous reviews. STUDY SELECTION: Randomized controlled trials that compared therapeutic hypothermia to normothermia for newborns with HIE. INTERVENTION: Therapeutic hypothermia. MAIN OUTCOME MEASURES: Death or major neurodevelopmental disability at 18 months. RESULTS: Seven trials including 1214 newborns were identified. Therapeutic hypothermia resulted in a reduction in the risk of death or major neurodevelopmental disability(risk ratio [RR], 0.76; 95% CI, 0.69-0.84) and increase in the rate of survival with normal neurological function (1.63; 1.36-1.95) at age 18 months. Hypothermia reduced the risk of death or major neurodevelopmental disability at age 18 months in newborns with moderate HIE (RR, 0.67; 95% CI, 0.56-0.81) and in newborns with severe HIE (0.83; 0.74-0.92). Both total body cooling and selective head cooling resulted in reduction in the risk of death or major neurodevelopmental disability(RR, 0.75; 95% CI, 0.66-0.85 and 0.77; 0.65-0.93,respectively). CONCLUSION: Hypothermia improves survival and neurodevelopment in newborns with moderate to severe HIE.Total body cooling and selective head cooling are effective methods in treating newborns with HIE. Clinicians should consider offering therapeutic hypothermia as part of routine clinical care to these newborns. PMID- 22312167 TI - Genetic and environmental influences on individual differences in sedentary behavior during adolescence: a twin-family study. AB - OBJECTIVE: To investigate the degree to which genetic and environmental influences affect individual differences in sedentary behavior throughout adolescence. DESIGN: Cross-sectional twin-family design. SETTING: Data on self reported sedentary behavior from Dutch twins and their nontwin siblings. PARTICIPANTS: The total sample consisted of 5074 adolescent twins (aged 13-19 years) and 937 siblings (aged 12-20 years) from 2777 families. MAIN OUTCOME MEASURES: Screen-viewing sedentary behavior was assessed with survey items about weekly frequency of television viewing, playing electronic games, and computer/Internet use. Based on these items,an overall score for screen-viewing sedentary behavior was computed. RESULTS: The genetic architecture of screen viewing sedentary behavior differed by age. Variation in sedentary behavior among 12-year-olds was accounted for by genetic (boys: 35%; girls: 19%), shared environmental (boys:29%; girls: 48%), and nonshared environmental (boys:36%; girls: 34%) factors. Variation in sedentary behavior among 20-year-olds was accounted for by genetic(boys: 48%; girls: 34%) and nonshared environmental(boys: 52%; girls: 66%) factors. CONCLUSION: The shift from shared environmental factors in the etiology of sedentary behavior among younger adolescents to genetic and nonshared environmental factors among older adolescents requires age-specific tailoring of intervention programs. PMID- 22312168 TI - Poor outcomes at discharge among extremely premature infants: a national population-based study. AB - OBJECTIVES: To assess risk factors and develop a simple estimate method for poor neonatal outcomes for specific groups of extremely premature infants at birth. DESIGN: Population-based study. SETTING: Israel National Very Low Birth Weight Infant Database. PARTICIPANTS: Infants born at 23 to 26 weeks' gestation between January 1, 1995, and December 31, 2008. INTERVENTION: We developed a tool to estimate poor neonatal outcomes for infants born at 24 to 26 weeks' gestation (n=2544) that incorporated factors at birth significantly associated with poor outcomes into a linear regression model. MAIN OUTCOME MEASURES: Poor neonatal outcomes defined as the composite of mortality or severe neurologic or pulmonary morbidity at discharge from the hospital. RESULTS: Major factors associated with poor outcomes at 24 to 26 weeks' gestation were gestational age, male sex, sex specific birth weight percentile, and lack of prenatal steroid therapy. Estimated poor outcomes for January 1, 2000, to December 31, 2008, were calculated as the sum of the percentages determined for each of the 4 parameters: (1) gestational age (26, 25, and 24 weeks; 0%, 17%, and 34%, respectively), (2) birth weight percentile (>75th, 25th-75th, and < 25th percentiles; 0%,13%, and 26%, respectively), (3) lack of prenatal steroids (16%), and (4) male sex (7%). There was also an intercept value of 25%. Estimated poor outcome rates for the 36 subgroups of infants ranged from 25% to 100%and correlated well with observed rates (intraclass correlation coefficient, 0.93). CONCLUSIONS: The combined outcomes of deaths or severe morbidities in the neonatal period of infants born at 24 to 26 weeks' gestation could be simply estimated at birth. The provision of an appropriate and up-to-date estimate of poor neonatal outcomes for specific infants may be useful in counseling families on treatment options for these infants. PMID- 22312169 TI - Human immunodeficiency virus disease severity, psychiatric symptoms, and functional outcomes in perinatally infected youth. AB - OBJECTIVE: To evaluate associations between human immunodeficiency virus (HIV) disease severity and psychiatric and functional outcomes in youth with perinatal HIV infection. DESIGN: Cross-sectional analysis of entry data from an observational,prospective 2-year study.Logistic and linear regression models adjusted for potential confounders were used. SETTING: Twenty-nine sites of the International Maternal Pediatrics Adolescent AIDS Clinical Trials Group study in the United States and Puerto Rico. PARTICIPANTS: Youth aged 6 to 17 years who had HIV infection (N=319). MAIN EXPOSURES: Antiretroviral treatment and perinatal HIV infection. MAIN OUTCOME MEASURES: Youth and primary caregivers were administered an extensive battery of measures that assessed psychiatric symptoms; cognitive, social,and academic functioning; and quality of life. RESULTS: Characteristics of HIV were a current CD4 percentage of 25% or greater (74% of participants), HIV RNA levels of less than 400 copies/mL (59%), and current highly active antiretroviral therapy (81%). Analyses indicated associations of past and current Centers for Disease Control and Prevention class C designation with less severe attention-deficit/hyperactivity disorder inattention symptoms,older age at nadir CD4 percentage and lower CD4 percentage at study entry with more severe conduct disorder symptoms,higher RNA viral load at study entry with more severe depression symptoms, and lower CD4 percentage atstudy entry with less severe symptoms of depression. There was little evidence of an association between specific antiretroviral therapy and severity of psychiatric symptoms.A lower nadir CD4 percentage was associated with lower quality of life, worse Wechsler Intelligence Scale for Children Coding Recall scores, and worse social functioning. CONCLUSION: Human immunodeficiency virus illness severity markers are associated with the severity of some psychiatric symptoms and, notably, with cognitive, academic,and social functioning, all of which warrant additional study. PMID- 22312171 TI - Efficiency of neonatal screening for congenital adrenal hyperplasia due to 21 hydroxylase deficiency in children born in mainland France between 1996 and 2003. AB - OBJECTIVE: To assess the efficiency of the French national screening program for 21-hydroxylase deficiency (21-OHD). Neonatal screening for congenital adrenal hyperplasia due to 21-OHD is mainly intended to prevent death due to salt wasting but remains controversial because of the number of false-positive results and the ease with which most female cases can be identified by virilized genitalia at birth. DESIGN: Population-based study. SETTING: National neonatal screening program, pediatric endocrinologists nationwide, and reference center for genotyping. PARTICIPANTS: All neonates screened for 21-OHD in mainland France between January 1, 1996, and December 31, 2003. OUTCOME MEASURES: Screening efficiency indicators, disease severity, contribution of screening to early diagnosis, and disease-specific mortality before and during the study period. RESULTS: A total of 6,012,798 neonates were screened; results in 15,407 were considered positive for 21-OHD. Three hundred eighty-three cases were identified, giving a prevalence of 1 for every 15,699 births. The positive predictive value of screening was 2.3% (95% CI, 2.1%-2.6%), with a sensitivity of 93.5% (90.9% 95.9%) and a specificity of 99.7% (99.7%-99.7%). The false-positive rate was particularly high in preterm infants, for which the positive predictive value was 0.4% (95% CI, 0.2%-0.5%). Screening allowed clinical diagnosis in 162 of 383 cases (42.3%), with the others being detected clinically or through family history. There was a trend toward declining neonatal mortality due to 21-OHD. CONCLUSIONS: In this large population-based study, the efficiency of routine 21 OHD screening was moderate in neonates born at term and very low in preterm neonates. We recommend the discontinuation of screening, as currently performed in France, in preterm neonates. PMID- 22312170 TI - Multicenter study of neurodevelopment in 3-year-old children with and without single-suture craniosynostosis. AB - OBJECTIVE: To evaluate the hypothesis that 3-year-old children with single-suture craniosynostosis would receive lower neurodevelopmental scores than a comparable group of children born with patent sutures. DESIGN: Longitudinal comparison study. SETTING: Five tertiary care craniofacial centers. PARTICIPANTS: Patients with craniosynostosis (cases) and a comparison group of children without craniosynostosis(controls). Patients diagnosed with single-suture craniosynostosis from 2002 to 2006 were eligible as cases.Controls were frequency matched to cases on age, sex, race, socioeconomic status, and study site. MAIN EXPOSURE: Craniosynostosis. MAIN OUTCOME MEASURES: We administered the Bayley Scales of Infant Development, Second Edition, mental and motor development indices and the Preschool Language Scales, Third Edition, receptive and expressive communication scales. Children were evaluated at baseline (before surgery in cases and at a similar age in controls)and at 18 and 36 months of age. We compared the groups' performances at 36 months by fitting adjusted linear and logistic regression models. We also estimated adjusted associations between age at surgery and neurodevelopmental scores. RESULTS: Adjusted mean case deficits ranged from 3 to 6 points (P<= .008 for all comparisons). Compared with controls, the odds of cases being delayed ranged from 1.5 to 2.0, depending on the neurodevelopmental scale (P values ranged from .03 to .09). Cases' ages at craniosynostosis repair were not strongly related to neurodevelopmental performance. CONCLUSIONS: In this large, carefully controlled, multicenter study, we observed consistently lower mean neurodevelopmental scores in children with single-suture craniosynostosis compared with controls. These results provide further support for neurodevelopmental screening in young children with single suture craniosynostosis. PMID- 22312172 TI - Associations between sexuality education in schools and adolescent birthrates: a state-level longitudinal model. AB - OBJECTIVE: To examine the impact of sexuality education practices on adolescent birthrates while controlling for demographic characteristics and religious/political factors at a state level. DESIGN: Prospective cohort study. SETTING: Twenty-four states, from 1997 through 2005. PARTICIPANTS: Girls aged 15 to 17 years. MAIN EXPOSURE: The state sexuality education practices (ie, sexually transmitted disease prevention, pregnancy prevention, condom efficacy) for 1996 through 2004 from the Centers for Disease Control and Prevention School Health Profiles Survey. MAIN OUTCOME MEASURES: State birthrates for girls aged 15 to 17 years for 1997 through 2005 from the Centers for Disease Control and Prevention. RESULTS: In a longitudinal, unadjusted model, our findings provide evidence that increased sexuality education within school curricula is associated with lower adolescent birthrates (average sexuality education topics beta = -0.61; P = .001). However, the effect of sexuality education disappeared when taking into consideration the demographic characteristics, religiosity, and abortion policies of the state (average sexuality education topics beta = -0.12; P = .26). States with higher religiosity rankings and greater political conservatism had higher adolescent birthrates. CONCLUSIONS: The effects of sexuality education were constrained by state characteristics and do not independently explain the considerable variations in adolescent birthrates found across states. Our findings underscore the strong influence of state characteristics on adolescent birthrates above and beyond sexuality education, which must be considered when evaluating the efficacy of sexuality education programs. PMID- 22312174 TI - Student access to competitive foods in elementary schools: trends over time and regional differences. AB - OBJECTIVE: To examine the availability of competitive foods in elementary schools. DESIGN: Nationally representative mail-back survey. SETTING: United States public and private elementary schools during the 2006-2007, 2007-2008, 2008-2009, and 2009-2010 school years. PARTICIPANTS: Survey respondents at 2647 public and 1205 private elementary schools. MAIN OUTCOME MEASURE: The availability of foods offered in competitive venues. RESULTS: Elementary school students' access to foods in competitive venues on campus (vending machines, school stores, snack bars, or a la carte lines) remained constant over time. As of the 2009-2010 school year, approximately half of all public and private elementary school students could purchase foods in 1 or more competitive venues on campus. Sugary foods were available to almost all students with access to competitive foods on campus. Public elementary school students in the South had more access to competitive food venues and greater availability of salty and sweet products in those venues compared with students in other parts of the country; however, they also had greater availability of healthier foods, such as fruits and vegetables. CONCLUSIONS: Many elementary school students can purchase competitive foods on campus. Most students with access to competitive venues could purchase sweet products, but healthier foods were less widely available. PMID- 22312173 TI - The impact of schoolwide positive behavioral interventions and supports on bullying and peer rejection: a randomized controlled effectiveness trial. AB - OBJECTIVE: To build on prior research documenting the impact of School-wide Positive Behavioral Interventions and Supports (SWPBIS) on school climate and discipline problems to examine the extent to which it affects bullying and peer rejection during the transition into early adolescence. DESIGN: Three-level models were fit using hierarchical linear modeling to determine the effect of SWPBIS on children's involvement in bullying. SETTING: Thirty-seven Maryland public elementary schools. PARTICIPANTS: Data involved 12 344 children (52.9% male, 45.1% African American, 46.1% white) followed up longitudinally across 4 school years. INTERVENTION: A randomized controlled effectiveness trial of SWPBIS. OUTCOME MEASURES: Reports from teachers on bully-related behaviors were assessed through the Teacher Observation of Classroom Adaptation-Checklist. RESULTS: Analyses indicated that children in schools that implemented SWPBIS displayed lower rates of teacher-reported bullying and peer rejection than those in schools without SWPBIS. A significant interaction also emerged between grade level of first exposure to SWPBIS and intervention status, suggesting that the effects of SWPBIS on rejection were strongest among children who were first exposed to SWPBIS at a younger age. CONCLUSIONS: The results indicated that SWPBIS has a significant effect on teachers' reports of children's involvement in bullying as victims and perpetrators. The findings were considered in light of other outcomes for students, staff, and the school environment, and they suggest that SWPBIS may help address the increasing national concerns related to school bullying by improving school climate. PMID- 22312177 TI - Picture of the month--quiz case. Erythema ab igne. PMID- 22312178 TI - Solution-oriented policy research: using research to drive obesity prevention and control policies. PMID- 22312176 TI - Relationship between attrition and neurodevelopmental impairment rates in extremely preterm infants at 18 to 24 months: a systematic review. AB - OBJECTIVE: To assess the effect of loss to follow-up rates at 18 to 24 months on neurodevelopmental outcome statistics for infants of less than 1000 g birth weight or less than 28 weeks' gestational age. DATA SOURCES: MEDLINE, EMBASE, PubMed, and Cochrane Library databases (January 1, 2000, to June 30, 2010). STUDY SELECTION: We searched for studies reporting outcomes of infants of less than 1000 g birth weight or less than 28 weeks' gestational age who were born after 1990. MAIN EXPOSURE: Eligible articles had to report the primary outcome and follow-up rates at 18 to 24 months. MAIN OUTCOME: Our primary composite outcome of neurodevelopmental impairment (NDI) was any of a mental developmental quotient 2 SDs below the mean, using the Bayley Scales of Infant Development II; cerebral palsy; visual impairment; or significant hearing impairment. RESULTS: Of 43 publications describing outcomes at 18 to 24 months, 20 provided rates of follow up, describing a total of 34,185 infants. The NDI rates ranged between 12.4% and 57.5%. Follow-up rates ranged between 71.6% and 100%. Higher rates of NDI were significantly correlated with greater loss to follow-up (r(2) = 0.38, P = .007). Higher rates of both NDI and loss to follow-up were seen in the United States compared with Canada, the United Kingdom, Finland, Denmark, Austria, Germany, and Australia (r(2) = 0.70, P = .001). CONCLUSIONS: Ascertainment bias may overestimate NDI in extremely low-birth-weight or extremely low-gestational-age survivors at 18 to 24 months. Alternatively, the characteristics of different populations and health systems may contribute to higher rates of attrition and higher rates of NDI. PMID- 22312175 TI - Twelve-month outcomes of the loozit randomized controlled trial: a community based healthy lifestyle program for overweight and obese adolescents. AB - OBJECTIVES: To assess the outcomes of the Loozit adolescent weight management intervention and to evaluate the effect of additional therapeutic contact 12 months into the program. DESIGN: A 24-month, 2-arm randomized controlled trial. Results at 12 months are presented. SETTING: Community health center and children's hospital in Sydney, Australia. PARTICIPANTS: A total of 151 overweight or obese 13- to 16-year-olds. INTERVENTION: In the first 2 months (phase 1), participants received 7 adolescent and parent weekly sessions focused on lifestyle modification. From 2 to 24 months (phase 2), adolescents attended booster sessions once every 3 months. During phase 2, adolescents randomized to the additional therapeutic contact arm also received telephone coaching and electronic communications once every 2 weeks. OUTCOME MEASURES: Baseline to 12 month changes in body mass index z score and waist to height ratio (primary outcomes) and changes in metabolic, psychosocial, and behavioral variables. RESULTS: Of 151 randomized adolescents, 82.1% completed 12-month follow-up. Intent-to-treat analyses showed significant reductions in mean body mass index z score (-0.09; 95% CI, -0.12 to -0.06), waist to height ratio (-0.02; 95% CI, 0.03 to -0.01), total cholesterol level (-4 mg/dL; 95% CI, -8 to 0 mg/dL; to convert to millimoles per liter, multiply by 0.0259), and triglycerides level (geometric mean, -80 mg/dL; 95% CI, -88 to -71 mg/dL; to convert to millimoles per liter, multiply by 0.0113). Most psychosocial outcomes improved, including global self-worth, but there were few dietary, physical activity, or sedentary behavior changes. No difference was found in primary outcomes between participants who did or did not receive additional therapeutic contact. CONCLUSIONS: The Loozit randomized controlled trial produced a significant but modest reduction in body mass index z score and improved psychosocial outcomes at 12 months. Supplementary telephone and electronic contact provided no additional benefit at 12 months. Trial Registration anzctr.org.au Identifier: 12606000175572. PMID- 22312180 TI - Preventing birth defects with a healthy pregnancy diet. PMID- 22312179 TI - Perils and opportunities of comparative performance measurement. PMID- 22312181 TI - Centering of organic-inorganic hybrid liposomal cerasomes in electrospun gelatin nanofibers. AB - A study investigating the embedding of stabilized organic-inorganic liposomal cerasomes in gelatin nanofibers through the electrospinning of cerasome-dispersed gelatin aqueous solution is presented. Fluorescent and transmission electron microscopy confirm the embedding and centering of cerasomes in the electrospun nanofibers. A simple mechanism is proposed for the centering of cerasomes in gelatin nanofibers. The ability to incorporate cerasomes capable of encapsulating a variety of bioactive molecules provides a promising method to functionalize polymer nanofibers. PMID- 22312182 TI - Power voltage current convertor using quasi complementary MOSFET current mirrors. AB - A voltage current convertor is described having a quasi complementary class AB architecture that is particularly suited to implementation using discrete power MOSFETs. High-voltage mirror designs are presented, enabling the construction of sources with kilovolt compliance range, tens of watts of output power and greater than 100 kHz bandwidth. GOmega output impedance and distortion below 1% can be obtained with no trimming or transistor matching. PMID- 22312183 TI - Fluctuation modes of nanoconfined DNA. AB - We report an experimental investigation of the magnitude of length and density fluctuations in DNA that has been stretched in nanofluidic channels. We find that the experimental data can be described using a one-dimensional overdamped oscillator chain with nonzero equilibrium spring length and that a chain of discrete oscillators yields a better description than a continuous chain. We speculate that the scale of these discrete oscillators coincides with the scale at which the finite extensibility of the polymer manifests itself. We discuss how the measurement process influences the apparent measured dynamic properties, and outline requirements for the recovery of true physical quantities. PMID- 22312184 TI - Evolution of the Arctic Calanus complex: an Arctic marine avocado? AB - Before man hunted the large baleen whales to near extinction by the end of the nineteenth century, Arctic ecosystems were strongly influenced by these large predators. Their main prey were zooplankton, among which the calanoid copepod species of the genus Calanus, long considered key elements of polar marine ecosystems, are particularly abundant. These herbivorous zooplankters display a range of adaptations to the highly seasonal environments of the polar oceans, most notably extensive energy reserves and seasonal migrations to deep waters where the non-feeding season is spent in diapause. Classical work in marine ecology has suggested that slow growth, long lifespan and large body size in zooplankton are specific adaptations to life in cold waters with short and unpredictable feeding seasons. Here, we challenge this understanding and, by using an analogy from the evolutionary and contemporary history of the avocado, argue that predation pressure by the now nearly extinct baleen whales was an important driving force in the evolution of life history diversity in the Arctic Calanus complex. PMID- 22312185 TI - Identification of a novel CRYBB2 missense mutation causing congenital autosomal dominant cataract. AB - PURPOSE: To identify the genetic defect in a four-generation Croatian family presenting with autosomal dominant cataract. METHODS: Genome-wide linkage analysis with 250K single nucleotide polymorphism (SNP) arrays was performed using DNA from one unaffected and seven affected individuals. Mutation screening of candidate genes was performed by bidirectional Sanger sequencing. RESULTS: Evidence for linkage was observed for eight genomic regions. Among these was a locus on chromosome 22 which encompasses the beta-crystallin gene cluster. This cluster includes four genes, namely beta-crystallin B1 (CRYBB1), beta-crystallin B2 (CRYBB2), beta-crystallin B3 (CRYBB3), and beta-crystallin A4 (CRYBA4). A novel sequence variant was found in the CRYBB2 gene (p.Arg188His). This variant cosegregated with the disease phenotype in all affected individuals but was not present in the unaffected family members and 100 healthy control subjects. CONCLUSIONS: We report a novel missense mutation, p.Arg188His, in CRYBB2 associated with congenital cataract in a family of Croatian origin. This variant is the most COOH-terminal missense mutation in CRYBB2 that has been identified so far. PMID- 22312186 TI - Analysis of mitochondrial DNA variations in Indian patients with congenital cataract. AB - PURPOSE: Identification of mitochondrial DNA (mtDNA) variations in the inherited cataract patients from south India. METHODS: Three families with inherited cataract of maternal origin were evaluated. Clinical and ophthalmologic examinations were performed on available affected as well as unaffected family members. Samples of mtDNA were amplified using 24 pairs of overlapping primers to analyze the entire mitochondrial genome to screen for variations and analyzed for both coding and non-coding regions. Bioinformatic analysis was performed to evaluate the effect of nucleotide variations. RESULTS: DNA sequence analysis of inherited cataract families showed 72 nucleotide variations, of which 15 were observed in the major non-coding D-loop region, 3 in the tRNA genes, 5 in the rRNA genes, and 49 in the protein coding region. Among these variations 56 were reported previously and 16 were novel of which, 12 synonymous substitutions, 2 non-synonymous substitutions along with a frameshift mutation, and one was in the non-coding region. Nicotinamide adenine dinucleotide dehydrogenase (NADH) subunit (ND) gene of mtDNA was highly altered, in general, and found to contain 4 variations specific for cataract patients of the first family, six for the second, and one for the third family. CONCLUSIONS: Seventy-two variations were observed in three inherited cataract families. Four variations were specific for cataract patients of the first family, six for the second, and one for the third family. This is perhaps the first report on the presence of mitochondrial mutations in inherited cataracts. PMID- 22312188 TI - Coralliform cataract caused by a novel connexin46 (GJA3) mutation in a Chinese family. AB - PURPOSE: To identify a novel disease-causing mutation of the GJA3 (gap junction alpha-3 protein) gene in a Chinese family with autosomal dominant congenital cataract (ADCC). METHODS: One family was examined clinically. After informed consent was obtained, genomic DNA was extracted from the venous blood of all participants. Genetic linkage analysis was performed on the known genetic loci for ADCC with a panel of polymorphic markers, and then mutations were screened by direct sequencing. Whenever substitutions were identified in a patient, high resolution melt curve analysis (HRM) was performed on all available family members and 100 normal controls. Bioinformatics analysis was undergone by the Garnier-Osguthorpe-Robson (GOR) and the PolyPhen (polymorphism phenotyping) programs to predict the effect of variants detected on secondary structure and protein function of the GJA3 protein. RESULTS: Clinical examination and pedigree analysis revealed one four-generation family with congenital nuclear coralliform cataracts. Significant two-point LOD (linkage odd disequilibrium) score was generated at marker D13S292 (Z(max)=2.51, theta=0), and further linkage and haplotype studies confined the disease locus to 13q11-13. Mutations screening of GJA3 in this family revealed an A->T transversion at position 563 (p.N188I) of the cDNA sequence. This novel missense mutation co-segregated with the affected members of the pedigree, but is not present in the unaffected relatives or 100 normal individuals. Secondary structure prediction suggested that the mutant GJA8 188I would replace three turns "T" with three beta sheet "E" at amino acid 189 191 and a beta sheet "E" with a turn "T" at position 194. CONCLUSIONS: Novel missense mutation in the second extracellular loop (E2) was detected, causing coral-like opacities involving embryonic and fetal nucleus surrounded by blue punctate opacities in the cortical zone of the lens. The results further suggested that the extracellular loop was the mutation hotspot of GJA3. PMID- 22312187 TI - Age-dependent changes in rat lacrimal gland anti-oxidant and vesicular related protein expression profiles. AB - PURPOSE: Anti-oxidation and exocytosis are important for maintaining exocrine tissue homeostasis. During aging, functional and structural alterations occur in the lacrimal gland (LG), including oxidative damage to proteins, lipids, and DNA. The aims of the present study were to determine in the aging LG: a) the effects of aging on LG structure and secretory activity and b) changes in the expression of oxidative stress markers. METHODS: To address these goals, tear secretion composition and corneal impression cytology were compared between male Wistar rats of 2 (control) and 24 (aged) months. LG morphology and the expression levels of vitamin E and malonaldehyde (MDA) were evaluated to determine the anti-oxidant activity and lipid peroxidation, respectively. RT-PCR and western blot analysis were used for the analysis of Ras related in brain GTPase protein (Rab) and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins of the secretory machinery (i.e.; Rab 3d, Rab 27, vesicle-associated membrane protein-2 (Vamp-2), and syntaxin). RESULTS: Histological analysis of aged rats revealed a higher frequency of corneal epithelia metaplasia. In the acinar cells, organelles underwent degeneration, and lipofucsin-like material accumulated in the cytoplasm along with declines in the anti-oxidant marker vitamin E. Rab3d and Rab27b mRNA levels fell along with Rab3d protein expression, whereas syntaxin levels increased. CONCLUSIONS: These findings indicate that exocytotic and anti-oxidant mechanisms become impaired with age in the rat LG. In parallel with these structural alterations, functional declines may contribute to the pathophysiology caused by tear film modification in dry eye disease. PMID- 22312189 TI - Missense mutation outside the forkhead domain of FOXL2 causes a severe form of BPES type II. AB - PURPOSE: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a developmental disease characterized by a complex eyelid malformation associated or not with premature ovarian failure (POF). BPES is essentially an autosomal dominant disease, due to mutations in the forkhead box L2 (FOXL2) gene, encoding a forkhead transcription factor. More than one hundred unique FOXL2 mutations have been described in BPES in different populations, many of which are missense mutations in the forkhead domain. Here, we report on a very severe form of BPES resulting from a missense mutation outside the forkhead domain. METHODS: A clinical and molecular genetic investigation was performed in affected and unaffected members of an Iranian family with BPES. The FOXL2 coding region was sequenced in an index case. Targeted mutation testing was performed in 8 family members. RESULTS: We have identified a heterozygous FOXL2 missense mutation c.650C->G (p.Ser217Cys) co-segregating with disease in members of a three generation family with BPES type II. Only few missense mutations have been reported outside the forkhead domain so far. They were all found in mild BPES, in line with in vitro studies demonstrating mostly normal localization and normal or increased transactivation properties of the mutant proteins. Unlike previous studies, affected members of the family studied here showed a severe BPES phenotype, with bilateral amblyopia due to uncorrected ptosis. CONCLUSIONS: This is the first study demonstrating a severe BPES phenotype resulting from a FOXL2 missense mutation outside the forkhead domain, expanding our knowledge about the phenotypic consequences of missense mutations outside the forkhead domain in BPES. PMID- 22312190 TI - Expression of T-helper-associated cytokines in patients with type 2 diabetes mellitus with retinopathy. AB - PURPOSE: Recent studies showed that immunological mechanisms were involved in the pathogenesis of diabetic retinopathy (DR). T-helper (Th) cells play an important role in chronic inflammatory disorders and autoimmune diseases. Whether Th cells participate in the pathogenesis of DR remains unclear. METHODS: To evaluate the role of Th cells in the pathogenesis of type 2 diabetes mellitus with retinopathy, the concentrations of interferon (IFN)-gamma, interleukin (IL) 1beta, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12 p70, IL-13, IL-17A, IL-22, and tumor necrosis factor (TNF)-alpha in the serum of 29 patients with type 2 diabetes mellitus and 30 normal controls were measured with FlowCytomix Technology. IL-22 levels in unstimulated and stimulated peripheral blood mononuclear cells (PBMCs) were examined with enzyme-linked immunosorbent assay. RESULTS: We found that the mean IL-22 serum levels were slightly lower in diabetic patients than in normal controls. The IL-22 level of PBMCs was significantly elevated in patients with proliferative diabetic retinopathy compared with the level in patients with non-proliferative diabetic retinopathy, patients with non-DR, and healthy controls. Additionally, the IL-22 serum and PBMC levels were positively correlated with the duration of diabetes. Serum levels of other associated cytokines showed no significant change in diabetic patients compared to controls. CONCLUSIONS: These results indicate a possible role of Th22 cells in DR, and IL-22 may be involved more in the pathogenesis of proliferative diabetic retinopathy than in other stages of DR. PMID- 22312191 TI - Familial discordance in Stargardt disease. AB - PURPOSE: To report genetic and phenotypic discordance across two generations of a family with autosomal recessive Stargardt disease (STGD1) and to compare pathogenicities of the G1961E and A1038V alleles of the ATP-binding cassette transporter, subfamily A, member 4 (ABCA4) gene. METHODS: Five members of a family with STGD1 (patients 1-4, affected; patient 5, carrier) were included. Clinical assessment was performed together with fundus autofluorescence and spectral domain-optical coherence tomography. Patients were stratified based on the results of electroretinogram testing. Genotyping of the ABCA4 gene was performed with the ABCR500 microarray. RESULTS: STGD1 was diagnosed in the male proband and his female sibling (patients 1 and 2, respectively). Two children of patient 2 (patients 3 and 4) were also affected. Genotyping revealed the W663X stop mutation in all affected patients. Patients 3 and 4, who were compound heterozygous for the G1961E mutation, had earlier ages of onset than patients 1 and 2, who were compound heterozygous for the A1038V mutation. Patient 1 had an age of onset 28 years younger than patient 2, whose delayed onset can be explained by relative foveal sparing, while patient 4 had an age of onset 44 years younger than patient 2. CONCLUSIONS: The G1961E mutation, which has been considered "mild," yields a more severe phenotype in this family than the A1038V mutation, which has been considered "severe." Marked intrasibship discordance in clinical course is described, suggesting an additional role for modifying factors in ABCA4 pleiotropism. PMID- 22312192 TI - TCCR/WSX-1 is a novel angiogenic factor in age-related macular degeneration. AB - PURPOSE: Age-related macular degeneration (AMD) is the major cause of blindness among persons aged 60 years and older. The current approved therapies for AMD are exclusively limited to inhibiting vascular endothelial growth factor. However, substantial improvement in vision occurs in only one-third of patients treated with vascular endothelial growth factor antagonists, and one-sixth of treated patients still progress to legal blindness. Therefore, more specific targets are needed to treat AMD. Our goal was to find secretory proteins that change in number in the aqueous humor and that cause exudative AMD disease. METHODS: The number of molecules changed in the aqueous humor of patients with AMD compared to the control group was determined using antibody array analysis. The levels of angiopoietin-2 and insulin-like growth factor binding protein-related protein 7 were measured using enzyme-linked immunosorbent assay. The levels of T-cell cytokine receptor (TCCR/WSX-1) were determined using western blot. Potential TCCR/WSX-1-mediated effects on tube formation as well as phosphorylation of extracellular signal-regulated kinase in human umbilical vein endothelial cells were determined. RESULTS: We found that the numbers of several molecules were changed in the aqueous humor of patients with AMD compared to the control group. Among them, angiopoietin-2 was reduced by 20% and TCCR/WSX-1 was increased twofold. Moreover, exogenous TCCR protein induced tube formation and phosphorylation of extracellular signal-regulated kinase in human umbilical vein endothelial cells. CONCLUSIONS: Our study suggests that TCCR/WSX-1 is closely associated with angiogenesis and could serve as a novel therapeutic target in patients with AMD. PMID- 22312194 TI - Transvaginal ultrasonography: a survey of the acceptability and its predictors among a native African women population. AB - OBJECTIVE: To determine the acceptability of transvaginal ultrasonography (TVU) and associated factors among Nigerian women. METHOD: A cross-sectional survey was conducted among 3137 women who presented for transabdominal ultrasound scan between August and November 2010 in two referral hospitals in Nigeria. Data were obtained using a questionnaire. Descriptive and multivariate analysis was performed applying logistic regression analysis; predictors of willingness of participants regarding transvaginal ultrasound were identified using SPSS Statistics (SPSS Inc, Chicago, IL) version 17 software. RESULTS: The mean age of the women was 33.8 years (standard deviation = 7.9), with 88.8% currently married. About 84% were willing to have TVU, while 54.2% were indifferent about the gender of the sonologist. About 17.3% believed that the procedure is painful. Significant predictors of willingness to have TVU were previous sexual experience and douching, prior painful vaginal examination, and vaginal surgery. CONCLUSION: The majority of Nigerian women expressed a willingness to have the TVU procedure without necessarily opting for any gender preference of the operator. Women should be adequately counseled on the operations of the procedure so as to be able to psychologically prepare for them. PMID- 22312195 TI - Attitudes toward female circumcision among Somali immigrants in Oslo: a qualitative study. AB - Due to its negative impact on public health, female circumcision (FC) has gained increased attention from international communities and the Norwegian public in recent decades. In 1995, the Norwegian government outlawed the practice and simultaneously developed a package of measures aimed at preventing and ultimately eradicating FC in Norway. Like many other Western countries, immigrants of Somali descent constitute the largest immigrant group in Norway from countries with FC traditions. Although this immigrant group is often perceived as a cultural society that supports FC generally as a practice, there appears to be a lack of studies that explore the impact of acculturation and the Western social context on Somali immigrants' attitudes toward the practice. Against this background, this paper explores the attitudes of Somalis living in Oslo, Norway to the practice of FC. Findings from this qualitative study indicate that Somalis in Oslo have, to a large extent, changed their attitude toward the practice. This was proven by the presence in Oslo of a large number of Somali parents who left their daughters uncut as well as Somali girls, boys, men, and women who attribute being uncircumcised a high status. This study adds to the knowledge of the process of abandonment of FC among immigrants in the Western countries. The study highlights the success that has been achieved in improving attitudes toward the practice of the Somali community in Oslo, Norway, as well as emerging challenges that need to be addressed further. PMID- 22312193 TI - Non-housekeeping genes expressed in human trabecular meshwork cell cultures. AB - PURPOSE: To identify non-housekeeping genes definitively expressed in the human trabecular meshwork (TM). METHODS: Microarray gene expression data on TM cultured cells from four studies were compared. Genes that were queried in at least three studies and assessed to be expressed in at least three studies were considered definitively expressed genes of the human TM. Housekeeping genes were removed from this set of genes. The non-housekeeping TM gene profile was analyzed for pathway enrichment and microRNA targeting, using bioinformatics tools. The results were compared with results of previous non-array based studies. RESULTS: Nine hundred and sixty-two genes were identified as non-housekeeping TM expressed genes. Analysis of these by Kyoto Encyclopedia of Genes and Genomes led to identification of two enriched biologic pathways that achieved a highly significant Bonferroni p-value (p<=0.01): focal adhesion and extracellular matrix (ECM)-receptor interaction. Many of the genes were previously implicated in TM related functions and the TM-associated disease glaucoma; however, some are novel. MicroRNAs known to be expressed in the trabecular meshwork were predicted to target some of the genes. Ten genes identified here, ALDH1A1 (aldehyde dehydrogenase 1 family, member A1), CDH11 (cadherin 11, type 2, OB-cadherin), CXCR7 (chemokine (C-X-C motif) receptor 7), CHI3L1 (chitinase 3-like 1), FGF2 (fibroblast growth factor 2), GNG11 (guanine nucleotide binding protein [G protein], gamma 11), IGFBP5 (insulin-like growth factor binding protein 5), PTPRM (protein tyrosine phosphatase, receptor type, M), RGS5 (regulator of G-protein signaling 5), and TUSC3 (tumor suppressor candidate 3), were also reported as TM expressed genes in three earlier non-microarray based studies. CONCLUSIONS: A transcriptome consisting of 962 non-housekeeping genes definitively expressed in the human TM was identified. Multiple genes and microRNAs are proposed for further study for a better understanding of TM physiology. PMID- 22312197 TI - The catastrophic collapse of morale among hospital physicians in Japan. AB - The past few decades have witnessed bleak pictures of unhappy physicians worldwide. Japanese physicians working in hospitals are particularly distressed. Today, Japan's healthcare system is near collapse because physicians are utterly demoralized. Their loss of morale is due to budget constraints, excessive demands, physician shortages, poor distribution, long working hours, hostile media, increasing lawsuits, and violence by patients. Severe cost-saving policies, inadequate distribution of healthcare resources, and the failure to communicate risks has damaged physicians' morale and created conflicts between physicians and society. Physicians should communicate the uncertainty, limitations, and risks of modern medicine to all members of society. No resolution can be achieved unless trust exists between physicians, patients, the public, the media, bureaucrats, politicians and jurists. PMID- 22312196 TI - Estrogen formulations and beauty care practices in Japanese women. AB - PURPOSE: Traditionally, oral estrogens have been used for hormone replacement therapy. However, in Japan, additional estrogen formulations have been used, including transdermal patches and transdermal gels. The latter have a unique commonality with cosmetics because both of them are applied to the skin. Beauty care is one of the most important lifestyle factors for women, and it has been reported that the amount of attention paid to beauty care has an effect in determining whether or not women will choose to undergo HRT during menopause. Therefore, our study focused on estrogen formulations and beauty care practices. PATIENTS AND METHODS: Fifty women who use hormone replacement therapy were recruited from the outpatient clinic of Tohoku University Hospital. They were treated with oral conjugated estrogen (n = 11), transdermal 17beta-estradiol patch (n = 11), and transdermal 17beta-estradiol gel (n = 28). They completed a questionnaire to assess their lifestyle (beauty care practices and exercise habits) and their compliance. The transdermal gel users were further interviewed about their subjective impressions regarding "smell", "sticky feeling", "spreadability", and "irritation" on the skin using a five-grade scale. RESULTS: There were no differences in the usability of medicines and patient compliance among the estrogen formulations. We observed a positive tendency between the level of beauty care and transdermal gel use (P = 0.0645, ordinary logistic regression analysis). The gel users placed top priority on a lack of "sticky feeling" but the subjective impression regarding "sticky feeling" was worst among the four factors (P < 0.01, Steel-Dwass test). Correspondence analysis showed that the subjective impressions of transdermal gel corresponding to usability in the range of "moderate" to "very good" and "sticky feeling" greatly affected the usability of the formulation. CONCLUSION: These results suggest that the level of attention to beauty care plays some role in the choice of estrogen formulations. PMID- 22312198 TI - Vulnerability and risk perception in the management of HIV/AIDS: Public priorities in a global pandemic. AB - Understanding the way perception of risk is shaped and constructed is crucial in understanding why it has been so difficult to mitigate the spread of HIV/AIDS. This paper uses the Pressure and Release (PAR) model, used to predict the onset of natural disasters as the conceptual framework. It substitutes vulnerability and risk perception as the trigger factors in the model, in making the case that HIV/AIDS can be characterized as a slow onset disaster. The implications are that vulnerability must be managed and reduced by addressing root causes, dynamic pressures, and unsafe conditions that contribute to the HIV/AIDS pandemic. HIV/AIDS programs must be culturally appropriate and work toward influencing risk perception, while addressing social norms and values that negatively impact vulnerable populations. By impacting cultural and social expectations, individuals will be able to more readily adopt safer sex behaviors. The development of policies and programs addressing the issues in context, as opposed to individual behaviors alone, allows for effective public health intervention. This may have implications for public health measures implemented for combating the spread of HIV/AIDS. PMID- 22312199 TI - The costs of breast cancer in a Mexican public health institution. AB - Breast cancer (BC) is the second leading cause of death as a result of neoplasia in Mexico. This study aimed to identify the direct and indirect costs of treating female outpatients diagnosed with BC at a Mexican public hospital. A cross sectional, observational, analytical study was conducted. A total of 506 medical records were analyzed and 102 were included in the cost analysis. The micro costing process was used to estimate treatment costs. A 17-item questionnaire was used to obtain information on direct and indirect costs. Of the 102 women with BC included in the study, 92.2% (94) were at Stage II, and only 7.8% at Stage I. Total direct costs over six months for the 82 women who had modified radical mastectomy (MRM) surgury were US$733,821.15. Total direct costs for the 15 patients with conservative surgery (CS) were US$138,190.39. We found that the total economic burden in the study population was much higher for patients with MRM than for patients with CS. PMID- 22312200 TI - Non-specialized inpatient care provided by university hospitals in Japan. AB - In Japan, all citizens are covered by the national insurance system in which universal free access to healthcare services is promised to everybody. Even in tertiary care university hospitals, considerable numbers of secondary care inpatients are supposed to be treated. We studied the mixed state of secondary care and tertiary care in university hospitals in Japan and its year-to-year trend. Based on the results of a national survey, we could statistically classify Japanese case-mix classification into 821 groups that are supposed to need tertiary care (group A) and 296 groups that are supposed to need secondary care (group B). Sixty percent of patients admitted to the university hospitals belonged to group A, and 25% belonged to group B. Despite of the implementation of government policies to differentiate functions of hospitals, there was no trend toward an increase in the rate of tertiary care and decrease in the rate of secondary care from 2003 to 2006. Patient behavior to seek tertiary care was simply influenced by distance from university hospital. However, behavior of patients to seek secondary care was significantly influenced by distance to adjacent general hospitals and seize of these hospitals. PMID- 22312201 TI - 30-days mortality in patients with perforated peptic ulcer: A national audit. AB - BACKGROUND: In 2005, The Danish National Indicator Project (DNIP) reported findings on patients hospitalized with perforated ulcer. The indicator "30-days mortality" showed major discrepancy between the observed mortality of 28% and the chosen standard (10%). RATIONALE: An audit committee was appointed to examine quality problems linked to the high mortality. The purpose was to (i) examine patient characteristics, (ii) evaluate the appropriateness of the standard, and (iii) audit all cases of deaths within 30 days after surgery. METHODS: Four hundred and twelve consecutive patients were included and used for the analyses of patient characteristics. The evaluation of the standard was based on a literature review, and a structured audit was performed according to the 115 deaths that occurred. RESULTS: The mean age was 69.1 years, 42.0% had one co morbid disease and 17.7% had two co-morbid diseases. 45.9% had an American Association of Anaesthetists score of 3-4. We found no results on mortality in studies similar to ours. The audit process indicated that the postoperative observation of patients was insufficient. DISCUSSION: As a result of this study, the standard for mortality was increased to 20%, and the new indicators for postoperative monitoring were developed. The DNIP continues to evaluate if these initiatives will improve the results on mortality. PMID- 22312202 TI - Legal intervention against medical accidents in Japan. AB - The number of civil lawsuits in Japan concerning medical accidents has been increasing gradually. Emotional reports in the media about medical accidents have amplified people's distrust of physicians. Since 2002, the police have been more actively involved, and the number of criminal prosecutions against physicians as a result of medical accidents has increased. Fear of litigation and arrest has demoralized physicians. Communication of the risks associated with various medical practices is considered vital if physician-patient relationships are to be improved. Moreover, there needs to be a reconsideration of legal interventions into medical affairs. PMID- 22312203 TI - Association of overweight and obesity with health status, weight management, and exercise behaviors among individuals with type 2 diabetes mellitus or with cardiometabolic risk factors. AB - OBJECTIVES: This investigation evaluated the role of obesity in health status and behaviors for weight management and exercise among individuals with type 2 diabetes mellitus (T2DM) or cardiometabolic risk factors. METHODS: Self-reported health status, exercise behaviors, and weight management were assessed in the SHIELD study for respondents with T2DM or high risk (HR) for diabetes (ie, >=3 of the following: abdominal obesity, body mass index [BMI] >=28 kg/m(2), self reported diagnosis of dyslipidemia, hypertension, or history of cardiovascular disease). Respondents were stratified into three BMI categories: <25 kg/m(2) (underweight or normal weight), 25.0-29.9 kg/m(2) (overweight), and >=30 kg/m(2) (obese), with comparisons made using analysis of variance. Comparisons between T2DM and HR were made using chi-square tests. RESULTS: T2DM (n =3,918) and HR (n =5,464) groups were similar for age (mean =59 years), race (>=85% white), and obesity. Overweight (31%) or obese T2DM (18%) respondents were significantly less likely to report excellent health compared with overweight or obese HR respondents (42% and 30%, respectively), p < 0.001. There were no differences between T2DM and HR groups for exercise behaviors. More obese respondents (20% T2DM, 21% HR) were "contemplating exercising", and fewer (21%-23%) were currently "exercising regularly" compared with overweight and normal weight respondents, p < 0.001. More obese respondents (78% T2DM, 83% HR) attempted weight management than normal (28%-35%) or overweight (57%-61%) respondents, p < 0.001. CONCLUSIONS: Obesity was negatively associated with self-perception of current health, exercising regularly, and weight maintenance for those with or at risk for diabetes. PMID- 22312205 TI - The practice and regulatory requirements of naturopathy and western herbal medicine in Australia. AB - Australian health workforce regulation is premised on the need to protect public health and safety. Specific criteria are set out by governments to ascertain the degree of risk and the need for government intervention. A study was undertaken to understand the current state of usage and the practice of naturopathy and western herbal medicine, and to ascertain whether statutory regulation was warranted. We found increased use of these complementary therapies in the community, with risks arising from both the specific practices as well as consumers negotiating a parallel primary health care system. We also found highly variable standards of training, a myriad of professional associations, and a general failure of current systems of self-regulation to protect public health and safety. Statutory regulation was the preferred policy response for consumers, insurers, general practitioners, and most of the complementary therapists. While we found a case for statutory registration, we also argue that a minimalist regulatory response needs to be accompanied by other measures to educate the public, to improve the standards of practice, and to enhance our understanding of the interaction between complementary and mainstream health care. PMID- 22312206 TI - Evidence-based decision-making within the context of globalization: A "Why-What How" for leaders and managers of health care organizations. AB - In the globalized knowledge economy, the challenge of translating knowledge into policy and practice is universal. At the dawn of the 21st century, the clinicians, leaders, and managers of health care organizations are increasingly required to bridge the research-practice gap. A shift from moving evidence to solving problems is due. However, despite a vast literature on the burgeoning field of knowledge translation research, the "evidence-based" issue remains for many health care professionals a day-to-day debate leading to unresolved questions. On one hand, many clinicians still resist to the implementation of evidence-based clinical practice, asking themselves why their current practice should be changed or expanded. On the other hand, many leaders and managers of health care organizations are searching how to keep pace with the demand of actionable knowledge. For example, they are wondering: (a) if managerial and policy innovations are subjected to the same evidentiary standards as clinical innovations, and (b) how they can adapt the scope of evidence-based medicine to the culture, context, and content of health policy and management. This paper focuses on evidence-based health care management within the context of contemporary globalization. In this paper, our heuristic hypothesis is that decision-making process related changes within clinical/managerial/policy environments must be given a socio-historical backdrop. We argue that the relationship between research on the transfer of knowledge and its uptake by clinical, managerial and policy target audiences has undergone a shift, resulting in increasing pressures in health care for intense researcher-practitioner collaboration and the development of "integrative KT platforms" at the crossroads of different fields (the field of knowledge management and the field of knowledge translation). The objectives of this paper are: (a) to provide an answer to the questions that health professionals ask most frequently about "Why" and "How" to bridge the know-do gap, (b) to illustrate by a Canadian example how the PRO ACTIVE program helps in closing the evidence-based practice gap. PMID- 22312204 TI - Public health measures during an anticipated influenza pandemic: Factors influencing willingness to comply. AB - This research assessed factors associated with willingness to comply with vaccination, isolation, and face mask wearing during an anticipated influenza pandemic. Data were collected from 2081 adults (16+) using a module of questions incorporated into the NSW Health Adult Population Health Survey. High levels of willingness to comply were reported with 73% either very or extremely willing to receive vaccination, 67% willing to isolate themselves, 58% willing to wear a face mask, and 48% willing to comply with all three behaviors. Further analysis indicated concern for self and family and higher levels of education were associated with high levels of willingness to comply. Younger people (16-24) were the least willing to comply; especially with wearing a face mask. Those with children reported higher levels of willingness to receive vaccination, and respondents who speak a language other than English at home were less willing to isolate themselves or comply with all behaviors. These findings provide a baseline measure of anticipated public compliance with key public health behaviors in the event of an influenza pandemic in the Australian population, and help to identify groups that may be more resistant to individual measures and may require additional attention in terms of risk communication strategies or health education. PMID- 22312207 TI - What are the emerging features of community health insurance schemes in East Africa? AB - BACKGROUND: The three East African countries of Uganda, Tanzania, and Kenya are characterized by high poverty levels, population growth rates, prevalence of HIV/AIDS, under-funding of the health sector, poor access to quality health care, and small health insurance coverage. Tanzania and Kenya have user-fees whereas Uganda abolished user-fees in public-owned health units. OBJECTIVE: To provide comparative description of community health insurance (CHI) schemes in three East African countries of Uganda, Tanzania, and Kenya and thereafter provide a basis for future policy research for development of CHI schemes. METHODS: An analytical grid of 10 distinctive items pertaining to the nature of CHI schemes was developed so as to have a uniform lens of comparing country situations of CHI. RESULTS AND CONCLUSIONS: The majority of the schemes have been in existence for a relatively short time of less than 10 years and their number remains small. There is need for further research to identify what is the mix and weight of factors that cause people to refrain from joining schemes. Specific issues that could also be addressed in subsequent studies are whether the current schemes provide financial protection, increase access to quality of care and impact on the equity of health services financing and delivery. On the basis of this knowledge, rational policy decisions can be taken. The governments thereafter could consider an option of playing more roles in advocacy, paying for the poorest, and developing an enabling policy and legal framework. PMID- 22312208 TI - Inpatient care of patients with type 1 diabetes mellitus by duration of diabetes and sex: A nationwide population-based longitudinal study. AB - AIMS: To describe hospitalizations of a cohort of patients with type 1 diabetes mellitus (T1DM) during 1973-1998 in the main complication groups by sex and T1DM lasting on average 9.5 or 16.5 years. MATERIAL AND METHODS: The population (N = 5166) consisted of all Finnish patients with T1DM diagnosed before the age of 18 years between 1965-1979, derived from the Finnish population-based register of T1DM patients. Data on hospitalizations were obtained from the Finnish Hospital Discharge Register. RESULTS: In the early stages of T1DM, the majority of the use of hospitalizations was due to the treatment of T1DM without complications. Enormous increases were found for complications when diabetes lasted longer (from 9.5 to 16.5 years). For women, the yearly number of bed-days for renal complications increased 4.8-fold, for peripheral vascular disease 4.3-fold, and for ophthalmic complications 2.5-fold. For men, the corresponding increases were as follows: 5-fold, 6.9-fold, and 2.5-fold. The yearly number of bed-days for nephropathy increased 7-fold. Bed-days for T1DM without complications dropped dramatically. The length of stay in hospitalizations decreased notably, but hospital visits increased when the duration of T1DM increased. CONCLUSIONS: Hospitalizations due to complications substantially increase with aging of T1DM patients. Prevention of T1DM is strongly needed. PMID- 22312210 TI - "Globalized public health." A transdisciplinary comprehensive framework for analyzing contemporary globalization's influences on the field of public health. AB - The current phase of globalization represents a "double-edged sword" challenge facing public health practitioners and health policy makers. The first "edge" throws light on two constructs in the field of public health: global health (formerly international health) and globalized public health. The second "edge" is that of global governance, and raises the question, "how can we construct public health regulations that adequately respond to both global and local complexities related to the two constructs mentioned earlier (global health and globalized public health)?" The two constructs call for the development of norms that will assure sustained population-wide health improvement and these two constructs have their own conceptual tools and theoretical models that permit a better understanding of them. In this paper, we introduce the "globalized public health" construct and we present an interactive comprehensive framework for critically analyzing contemporary globalization's influences on the field of public health. "Globalized public health", simultaneously a theoretical model and a conceptual framework, concerns the transformation of the field of public health in the sociohistorical context of globalization. The model is the fruit of an original theoretical research study conducted from 2005 to 2008 ("contextualized research," Gibbons' Mode II of knowledge production), founded on a QUAL-quant sequential mixed-method design. This research also reflects our political and ideological position, fuelled with aspirations of social democracy and cosmopolitical values. It is profoundly anchored in the pragmatic approach to globalization, looking to "reconcile" the market and equity. The model offers several features to users: (1) it is transdisciplinary; (2) it is interactive (CD ROM); (3) it is nonlinear (nonlinear interrelations between the contextual globalization and the field of public health); (4) it is synchronic/diachronic (a double-crossed perspective permits analysis of global social change, the emergence of global agency and the transmutation of the field of public health, in the full complexity of their nonlinear interaction); (5) it offers five characteristics as an auto-eco-organized system of social interactions, or dynamic, nonlinear sociohistorical system. The model features a visual interface (five interrelated figures), a structure of 30 "integrator concepts" that integrates 114 other element-parts via 1,300 hypertext links. The model is both a knowledge translation tool and an interactive heuristic guide designed for practitioners and researchers in public health/community health/population health, as well as for decision-makers at all levels. PMID- 22312209 TI - Visual impairment and age-related eye diseases in Florida: Findings from 2006 Behavioral Risk Factors Surveillance System (BRFSS) in Nine states. AB - PURPOSE: To compare the prevalence of age-related eye disease, visual impairment, and eye care service utilization among adults aged 65 and older in Florida with eight other states. METHODS: In 2006, nine states conducted the visual impairment and access to eye care module using the Behavioral Risk Factors Surveillance System (BRFSS) survey (N = 62,750). Visual impairment was based on self-reported ability to see distant and near objects. Age-related eye diseases including cataract, glaucoma, macular degeneration, and diabetic retinopathy were self reported with diagnosis confirmed by a health care professional. Eye care visit or examination was assessed by whether a respondent reported an eye visit or dilated eye examination within the past year. RESULTS: THE ESTIMATED PREVALENCE OF DISTANT AND NEAR VISUAL IMPAIRMENT WAS LOWER IN FLORIDA THAN IN THE EIGHT OTHER STATES (DISTANT: 11.5% vs 15.2%, P < 0.001; near: 22.3% vs 28.7%, P < 0.001). There was no significant difference with the prevalence of age-related macular degeneration and diabetic retinopathy between these two groups. The prevalence of glaucoma and cataract was higher in Florida. The rates of eye care visits (80.5% vs 74.8%, P < 0.01) and dilated eye examinations (74.7% vs 64.0%, P < 0.01) were higher in Florida. After controlling for demographic variables, chronic conditions, insurance, and eye examination, results for elderly in Florida continued to demonstrate less visually impaired. CONCLUSION: Fewer elderly in Florida reported visual impairment in spite of comparable or higher prevalence of age-related eye diseases with other states. Health care utilization and health insurance for eye care coverage were also higher in Florida, which may account for the phenomena. More research is needed to investigate the association. PMID- 22312211 TI - Improving regional variation using quality of care measures. AB - There is significant regional variability in the quality of care provided in the United States. This article compares regional performance for three measures that focus on transitions in care, and the care of patients with multiple conditions. Admissions for people with ambulatory care-sensitive conditions, hospital readmissions within 30 days of discharge, and compliance with practice guidelines for people with three chronic conditions (congestive heart failure, chronic obstructive pulmonary disease, and diabetes) were analyzed using data drawn from the Centers for Medicare & Medicaid Services' Standard Analytic Files for 5% of a 2004 national sample of Medicare beneficiaries which was divided by hospital referral regions and regional performance. There were significant regional differences in performance which we hypothesize could be improved through better care coordination and system management. PMID- 22312212 TI - Individualized initiation of statin therapy determined by baseline LDL-C: Are you more likely to achieve goal LDL-C? AB - Cardiovascular disease remains the leading cause of death in the world. A significant amount of clinical data are available to demonstrate the positive influence that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy has on slowing the progression of cardiovascular disease and improving clinical outcomes. Achieving the treatment goals for cholesterol in cardiovascular disease continues to present challenges. Recent clinical trial information is available assessing the use of more aggressive initial doses of statin therapy based on initial low-density lipoprotein cholesterol (LDL-C) measurements in an attempt to reach treatment goals sooner. Six clinical trials assessed low-, moderate- and high-risk individuals as well as those with type 2 diabetes mellitus to determine if this treatment approach is both safe and effective. The studies concluded that initial dosing of statin therapy determined by a baseline LDL-C measurement demonstrates good achievement in reaching treatment goals and does not result in a higher rate of adverse effects. PMID- 22312214 TI - Characterization and evaluation of the directly observed treatment for tuberculosis in Santiago de Compostela (1996-2006). AB - OBJECTIVE: To realize a retrospective study of the characterization, results, and effectiveness of directly observed therapy, short course (DOTS) in the regional health area of Santiago de Compostela (population 453 068) between 1996 and 2006. DESIGN: Tuberculosis (TB) patient cases involved in DOTS treatment were reviewed. The studied variables included: age, sex, type of TB, TB location, microbiological studies, chest radiology, pattern and treatment duration, final status of case, and TB recurrence. RESULTS: There were 2456 diagnosed TB cases in the time period studied and 259 received DOTS. The reasons for inclusion in this treatment strategy were social dystocia in 33.2% of cases, retreatment in 30.8% of cases, alcoholism in 29.3% of cases, drug use in 17.4% of cases, HIV coinfection in 11.6% of cases, multidrug-resistant strains of TB (MDR-TB) in 3.1%, and being an immigrant in 1.9% of cases. Primary TB represented 3.5% of the instances and pulmonary TB represented 87.6%. Bacteriological confirmation was performed in 76.8% of this population. Cavitated forms in chest radiology were shown in 46.7% of patients. Standard treatment guidelines were used in 71.4% of patients. Treatment adherence was achieved in 96.1% of the cases and 86.9% cases had a successful final status. Recurrence of TB was 1.5%. CONCLUSION: Although it is not possible to determine the exact influence of the DOTS strategy, its introduction under the conditions of the Galician Program for Prevention and Control of Tuberculosis (GPPCT)5 has worked to improve the control of tuberculosis in our health area. PMID- 22312213 TI - Postmortem computed tomography is an informative approach for prevention of sudden unexpected natural death in the elderly. AB - INTRODUCTION: Less than 10% of unnatural death cases have been examined by autopsy in Japan. In particular, the causes of death in the elderly have not yet been actively investigated. Here, we evaluated the possible use of postmortem computed tomography (PMCT) to investigate the causes of sudden unexpected natural death (SUND) in the elderly. METHODS AND SUBJECTS: Death cases confirmed within 24 hours since the onset of symptoms at the Emergency Department of Mie University Hospital were defined as sudden death cases. A total of 212 sudden death cases, including 175 SUND cases, that occurred in a 3-year period from September 2006 to August 2009 were investigated. RESULTS AND DISCUSSION: The number of sudden death cases was highest in patients in their seventies (56 cases, 26%), followed by patients in their eighties and sixties. Sudden death occurred more in men than in women in their fifties to seventies, while it occurred more in women than in men over the age of 90. PMCT was performed in more than 80% of SUND cases regardless of age of the deceased. The causes in 26 cases (27.1%) were established by PMCT, many of which were hemorrhagic diseases. Signs of aortic aneurysm rupture were detected by PMCT in the thoracic and abdominal areas of 8 patients in their seventies and over, whereas signs were absent in the younger group. Also, more than 18% of sudden death cases in patients in their seventies and over were bathing-related sudden death (BRSD). BRSD was rarely caused by hemorrhagic diseases, suggesting that a drop in blood pressure caused by bathing is an important factor in BRSD. CONCLUSION: PMCT is a method that is relatively acceptable by bereaved families. It is useful for establishing the causes of approximately 30% of the SUND cases examined. The PMCT findings suggested that early detection and treatment of thoracic and abdominal aortic aneurysms and preventive measurements of bathing-related drop in blood pressure are important for the prevention of SUND in the elderly. PMID- 22312215 TI - Impact of "noncaloric" activity-related factors on the predisposition to obesity in children. AB - The research related to childhood obesity generally emphasizes the impact of unhealthy eating and sedentary behavior as the main determinants of the predisposition to the positive energy balance that underlies excess body fat accumulation. Recent investigations have, however, demonstrated that "noncaloric" activity-related factors can induce a significant imbalance between spontaneous energy intake and energy expenditure. This is the case for short sleep duration that favors hormonal changes that increase hunger and energy intake. This agrees with our research experience demonstrating that short sleeping predicts the risk of obesity in children to a greater extent than sedentary behavior. Recent research by our team has also showed that demanding mental work promotes a substantial increase in energy intake without altering energy expenditure. In addition, our preliminary data suggest that the regular practice of school related cognitive efforts is predictive of an increase in abdominal fat accumulation. As discussed in this paper, individual variations in brain oxygenation and its related cerebral aerobic fitness might play a role in the relationship between mental work, energy intake, and the risk of excess body weight. PMID- 22312216 TI - A study of the changes in how medically related events are reported in Japanese newspapers. AB - Media reports of medically related events have a major effect on the healthcare community but there have been few detailed investigations conducted to investigate their content. The Nikkei Telecom 21 database was used to investigate the number of reports concerning medically related events between 1992 and 2007 in Japan's 5 national newspapers. For this period, both the total number of articles and the number of articles containing medically-related keywords were determined. The number of reports relating to medically related occurrences increased sharply from 1999 to 2000 and displayed a decrease from 2003 before increasing again in 2008. As of 2008, such reports account for 0.17% of total newspaper articles. The use of the word 'iryokago' (medical professional negligence or error) drastically increased in 1999 but showed a consistent decrease from 2004. On the other hand the frequency of reports relating to 'litigation' and 'punishment' increased rapidly in 1999 before leveling off. Despite this, the number of articles relating to medically related occurrences that were caused by doctor shortages and system errors increased sharply between 2006 and the present. Results indicate that the manner in which newspapers report medically related events is undergoing major changes. PMID- 22312217 TI - An integrated approach to preventing cardiovascular disease: community-based approaches, health system initiatives, and public health policy. AB - Cardiovascular disease (CVD) is largely the product of interactions among modifiable risk factors that are common in developed nations and increasingly of concern in developing countries. Hypertension is an important precursor to the development of CVD, and although detection and treatment rates have improved in recent years in some jurisdictions, effective strategies and policies supporting a shift in distribution of risk factors at the population level remain paramount. Challenges in managing cardiovascular health more effectively include factors at the patient, provider, and system level. Strategies to reduce hypertension and CVD should be population based, incorporate multilevel, multicomponent, and socioenvironmental approaches, and integrate community resources with public health and clinical care. There is an urgent need to improve monitoring and management of risk factors through community-wide, primary care-linked initiatives, increase the evidence base for community-based prevention strategies, further develop and evaluate promising program components, and develop new approaches to support healthy lifestyle behaviors in diverse age, socioeconomic, and ethnocultural groups. Policy and system changes are critical to reduce risk in populations, including legislation and public education to reduce dietary sodium and trans-fatty acids, food pricing policies, and changes to health care delivery systems to explicitly support prevention and management of CVD. PMID- 22312218 TI - Perceptions of risk: understanding cardiovascular disease. AB - Cardiovascular disease (CVD) is still the leading cause of death and disability worldwide despite the availability of well-established and effective preventive options. Accurate perception of a patient's risk by both the patient and the doctors is important as this is one of the components that determine health related behavior. Doctors tend to not use cardiovascular (CV) risk calculators and underestimate the absolute CV risk of their patients. Patients show optimistic bias when considering their own risk and consistently underestimate it. Poor patient health literacy and numeracy must be considered when thinking about this problem. Patients must possess a reasonably high level of understanding of numerical processes when doctors discuss risk, a level that is not possessed by large numbers of the population. In order to overcome this barrier, doctors need to utilize various tools including the appropriate use of visual aids to accurately communicate risk with their patients. Any intervention has been shown to be better than nothing in improving health understanding. The simple process of repeatedly conveying risk information to a patient has been shown to improve accuracy of risk perception. Doctors need to take responsibility for the accurate assessment and effective communication of CV risk in their patients in order to improve patient uptake of cardioprotective lifestyle choices and preventive medications. PMID- 22312220 TI - Protecting children: a survey of caregivers' knowledge of Georgia's child restraint laws. AB - INTRODUCTION: The leading cause of injury and death among children in the United States is motor vehicle crashes. Even though restraint laws are in place and public awareness campaigns and educational interventions have increased, many children are still improperly restrained or not restrained at all. When correctly used, child restraints significantly reduce risk of injury or death. METHODS: The purpose of the study was to elicit caregiver baseline knowledge of car seat installation and regulation before receiving car seat education from certified technicians at Inspection Station events. Inspection Station is a program whereby staff assists parents in correctly positioning car seats in participants' vehicles. Over an 8-week period, Safe Kids Cobb County Car Seat Technicians distributed a 16-item survey, with 10 knowledge-based questions and six demographic questions to Inspection Station participants. Descriptive statistics and t-tests were conducted to assess relationships between participant age, ethnicity, and gender with overall knowledge scores. Regression analysis was run to determine the association between participant education level and total child restraint knowledge. RESULTS: One hundred sixty-nine surveys were completed. Participant knowledge of vehicular child restraint ranged from 0% to 90% on all items. Only 29.6% of caregivers understood the proper tightness of the harness system. Less than half of the caregivers (43.8%) were aware of the Georgia law requiring children aged 6 years and younger to be in some type of child restraint. Only 43.2% of caregivers surveyed knew that children need to ride in a rear-facing child restraint until 1 year of age and 20 pounds. No significant correlations between participant knowledge and age were found. Statistically significant associations were found between total knowledge scores and education level, ethnicity, and gender. DISCUSSION: The results from this study describe baseline knowledge among a sample of participants at Inspection Station activities held in Cobb County, Georgia. These results can help inform tailoring of future programming so that the impact of enhanced health education/prevention messages for intended populations can be maximized and health child injury risk related to improper restraints can be minimized. PMID- 22312221 TI - Julie Rovner's Health Care Policy and Politics A to Z: a review. AB - Drawing on her vast experience covering health care policy on Capitol Hill, Julie Rovner has written explanations for over 300 key concepts that demystify the world of United States Government health care policy. In the newest edition of Health Care Policy and Politics A to Z, readers will find updated information on long-term health care spending, abortion, Medicaid and Medicare, health insurance and the uninsured, and the State Children's Health Insurance Program (SCHIP). New entries reflect important changes in recent years and include the Medicare Modernization Act, abstinence education, electronic health records, health savings accounts, and Project BioShield. The book does have its gaps, especially as it relates to mental health. However, this book should become a standard reference for all health care professionals. PMID- 22312222 TI - Utilization of preventive care services and their effect on cardiovascular outcomes in the United States. AB - OBJECTIVE: To describe and analyze utilization of preventive care services and their effect on cardiovascular outcomes in the United States. METHODS: Data from the 2007 Medical Expenditure Panel Survey (MEPS) were used to analyze utilization of preventive care services and their effect on cardiovascular outcomes. Recommendations by the Seventh Report of the Joint Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure and the National Cholesterol Education Program were used to determine appropriate levels of preventive care utilization. Utilization of blood pressure screening and cholesterol checkup services were used as the dependent variable, while age, gender, race, ethnicity, insurance status, and perceived health status were used as independent variables. Since guidelines differ for people with elevated blood pressure, respondents with elevated blood pressure were identified in the MEPS database by self-reported diagnosis. Descriptive statistics were used to describe the population, while a multivariate logistic regression model was built to predict odds of utilizing appropriate levels of preventive services. RESULTS: Total number of adult respondents for which data were available for blood pressure checkup and cholesterol checkup was 20,523 and 15,784, respectively. Overall, MEPS respondents were found to adhere to guideline recommendations for preventive care utilization. Multivariate logistic regression showed that odds of utilization of preventive care services were higher for elderly patients (age >65 years) for blood pressure (odds ratio [OR] = 2.39, 95% confidence interval [CI]: 1.92-2.97) and cholesterol (OR = 3.05, 95% CI: 2.18-4.27) preventive services compared with younger population (age 18-54 years). Males had much lower odds of getting blood pressure (OR = 0.33, 95% CI: 0.30-0.37) and cholesterol (OR = 0.59, 95% CI: 0.50-0.70) checks done compared with females. Odds of utilization were nearly similar for all races. Uninsured had lower odds for blood pressure (OR = 0.26, 95% CI: 0.23-0.30) and cholesterol (OR = 0.30, 95% CI: 0.24-0.39) checks compared with privately insured people. Asians had lower odds of getting blood pressure checkups compared to Whites (OR = 0.49, 95% CI: 0.39-0.63). Similar trends were recorded for other covariates such as race and perceived health status. CONCLUSION: The study was successful in identifying existing age, race, income, and insurance-status related disparities in preventive care utilization within a US population. PMID- 22312223 TI - Management of immigration and pregnancy screening in northeastern Italy. AB - This study assesses the impact of immigration in Friuli Venezia Giulia, a region of northeastern Italy, on the epidemiological features of hemoglobin patterns and on prothrombotic and trisomy risk in pregnancy for patients of non-Italian origin. This study follows a series of studies on the incidence of thalassemia and other hemoglobinopathies with reduced globin chain synthesis, that were performed during the postwar (1939-45) period in Friuli Venezia Giulia following immigration into the region from Istria and Sardinia (regions of northern and central Italy). Current data show that today's constantly growing immigration into the region differs from previous decades, in terms of origin and quantity of migrants, who mainly come from third world countries. This has a significant impact on health care issues, and more specifically on prospective health screening for foreigners. The authors conclude that scholastic education and hospital services, either public or private, and voluntary associations, may contribute to solving the problem, but only in terms of training and organization, for non-European Union citizens arriving in northern Italy and neighboring areas, especially those from Africa, Asia, Latin America, and eastern Europe. PMID- 22312226 TI - Improving the chemotherapy process and service to cancer patients. AB - The North Wales Cancer Treatment Centre (NWCTC) has to deal with an increasing demand in the number of patients who require chemotherapy, with the escalating use of second line, third line, and additional treatment for many cancers. As a result, there is growing pressure on the chemotherapy unit to deliver treatment quickly, efficiently, and safely. Following guidelines from the Department of Health's Manual for Cancer Services, we are constantly looking for ways to improve and develop the level of care provided at our center, and the process of receiving chemotherapy has been identified as an area of high risk. Therefore, a team was established to review and explore current practices at the NWCTC with the goal of implementing an improved process to minimize the risks of chemotherapy treatment. PMID- 22312225 TI - Anatomic considerations for central venous cannulation. AB - Central venous cannulation is a commonly performed procedure which facilitates resuscitation, nutritional support, and long-term vascular access. Mechanical complications most often occur during insertion and are intimately related to the anatomic relationship of the central veins. Working knowledge of surface and deep anatomy minimizes complications. Use of surface anatomic landmarks to orient the deep course of cannulating needle tracts appropriately comprises the crux of complication avoidance. The authors describe use of surface landmarks to facilitate safe placement of internal jugular, subclavian, and femoral venous catheters. The role of real-time sonography as a safety-enhancing adjunct is reviewed. PMID- 22312224 TI - Confidentiality of the medical records of HIV-positive patients in the United Kingdom - a medicolegal and ethical perspective. AB - This article examines the legal and ethical issues that surround the confidentiality of medical records, particularly in relation to patients who are HIV positive. It records some historical background of the HIV epidemic, and considers the relative risks of transmission of HIV from individual to individual. It explains the law as it pertains to confidentiality, and reports the professional guidance in these matters. It then considers how these relate to HIV-positive individuals in particular. PMID- 22312227 TI - Benefits and drawbacks of electronic health record systems. AB - The Health Information Technology for Economic and Clinical Health (HITECH) Act of 2009 that was signed into law as part of the "stimulus package" represents the largest US initiative to date that is designed to encourage widespread use of electronic health records (EHRs). In light of the changes anticipated from this policy initiative, the purpose of this paper is to review and summarize the literature on the benefits and drawbacks of EHR systems. Much of the literature has focused on key EHR functionalities, including clinical decision support systems, computerized order entry systems, and health information exchange. Our paper describes the potential benefits of EHRs that include clinical outcomes (eg, improved quality, reduced medical errors), organizational outcomes (eg, financial and operational benefits), and societal outcomes (eg, improved ability to conduct research, improved population health, reduced costs). Despite these benefits, studies in the literature highlight drawbacks associated with EHRs, which include the high upfront acquisition costs, ongoing maintenance costs, and disruptions to workflows that contribute to temporary losses in productivity that are the result of learning a new system. Moreover, EHRs are associated with potential perceived privacy concerns among patients, which are further addressed legislatively in the HITECH Act. Overall, experts and policymakers believe that significant benefits to patients and society can be realized when EHRs are widely adopted and used in a "meaningful" way. PMID- 22312229 TI - Providing and financing aged care in Australia. AB - This article focuses on the provision and financing of aged care in Australia. Demand for aged care will increase substantially as a result of population aging, with the number of Australians aged 85 and over projected to increase from 400,000 in 2010 to over 1.8 million in 2051. Meeting this demand will greatly strain the current system, and makes it important to exploit opportunities for increased efficiency. A move to greater beneficiary co-payments is also likely, though its extent may depend on whether aged care insurance and other forms of pre-payment can develop. PMID- 22312228 TI - Public health policies and management strategies for genital Chlamydia trachomatis infection. AB - Genital Chlamydia trachomatis is a sexually transmissible bacterial infection that is asymptomatic in the majority of infected individuals and is associated with significant short-term and long-term morbidity. The population prevalence of the infection appears to be increasing. C. trachomatis is of public health significance because of the impacts of untreated disease on reproductive outcomes, transmission of other sexually acquired infections, and the costs to health systems. At the individual level, C. trachomatis infection is readily treatable with antibiotics, although antibiotic resistance appears to be increasing. At the population level, public health control of spread of infection is more problematic. Approaches to control include primary preventive activities, increased access to testing and treatment for people with or at risk of infection, partner notification and treatment, and screening either opportunistically or as part of an organized population screening program. A combination of all of the above approaches is likely to be required to have a significant effect on the burden of disease associated with genital chlamdyia infection and to reduce population prevalence. The development of a vaccine for genital chlamydia infection could significantly reduce the public health burden associated with infection; however a vaccine is not expected to be available in the near future. PMID- 22312230 TI - Threat of mass resignation as a window of opportunity for questioning hospital service production structures in Finland. AB - BACKGROUND: Service production structures of public health care, once established, have proved extremely difficult to change. For this study, we reviewed discussions that took place in management teams at a Finnish central hospital over a period of nine months. The aim of the research was to analyze whether the management team meetings brought forth new and radical alternatives as to how service production could be reorganized. In addition to this, we were also interested in any possible problems that could be solved using these alternative models of service production, and also how preconditions to the application of different alternatives came about and how they eventually concluded. METHODS: Our data were derived from 24 management team meetings that took place between August 2007 and May 2008, and were fully videotaped. Data were collected from eight different management teams; the meetings of each were videotaped three times. The management teams reviewed represented three different hierarchical levels, ie, top management, division management, and operational unit management. Data were analyzed according to theory-based content analysis. As a theoretical framework, we utilized Kingdon's model to enable us to understand why some issues and problems are brought to the agenda of the change process and go on to become concrete policies while others fail to do so. RESULTS: During the study period, a threat of mass resignation of nursing staff caused a considerable change to the agenda of the management team meetings, introducing alternatives with the potential to renew the existing structures of operation in a radical manner. CONCLUSION: According to our analysis, the threat of mass resignation acted as a window of opportunity, linking the lack of nursing staff (problem) to operational and structural changes (alternative solutions). PMID- 22312219 TI - Improving health outcomes with better patient understanding and education. AB - A central plank of health care reform is an expanded role for educated consumers interacting with responsive health care teams. However, for individuals to realize the benefits of health education also requires a high level of engagement. Population studies have documented a gap between expectations and the actual performance of behaviours related to participation in health care and prevention. Interventions to improve self-care have shown improvements in self efficacy, patient satisfaction, coping skills, and perceptions of social support. Significant clinical benefits have been seen from trials of self-management or lifestyle interventions across conditions such as diabetes, coronary heart disease, heart failure and rheumatoid arthritis. However, the focus of many studies has been on short-term outcomes rather that long term effects. There is also some evidence that participation in patient education programs is not spread evenly across socio economic groups. This review considers three other issues that may be important in increasing the public health impact of patient education. The first is health literacy, which is the capacity to seek, understand and act on health information. Although health literacy involves an individual's competencies, the health system has a primary responsibility in setting the parameters of the health interaction and the style, content and mode of information. Secondly, much patient education work has focused on factors such as attitudes and beliefs. That small changes in physical environments can have large effects on behavior and can be utilized in self-management and chronic disease research. Choice architecture involves reconfiguring the context or physical environment in a way that makes it more likely that people will choose certain behaviours. Thirdly, better means of evaluating the impact of programs on public health is needed. The Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework has been promoted as one such potential approach. PMID- 22312231 TI - Implementation of artemether-lumefantrine treatment policy for malaria at health facilities in Tanzania. AB - BACKGROUND: The purpose of this study was to compare knowledge on the part of health workers in public and private health facilities about prescribing and dispensing of an artemether-lumefantrine combination, 3 years after moving from sulfadoxine-pyrimethamine to artemether-lumefantrine as a first-line treatment for nonsevere malaria in Tanzania. METHODS: A cross-sectional survey of a convenience sample of 306 dispensaries and pharmacies was conducted in Dar Es Salaam and the Coast region of Tanzania. Of these, 122 were community pharmacies, 143 were private dispensaries, and 41 were public dispensaries. Specific outcome measures were health workers' knowledge of the new malaria treatment guidelines, recommended doses of artemether-lumefantrine, and food requirements. RESULTS: A total of 489 health workers were included in the study. The respondents were prescribers in private dispensaries, public dispensaries, and community pharmacies. Participants included medical officers (3.7%), clinical officers (38%), pharmacists (5.7%), and pharmaceutical technicians (3.9%). Nearly all workers in the public dispensaries and about 50% of workers in private dispensaries and community pharmacies were aware of recommended first-line malaria treatment. The difference in the proportion of health workers with adequate knowledge about the new recommended antimalarial medicine in public and private dispensaries was statistically significant (P < 0.0001). There was a higher proportion of workers in public dispensaries who had adequate knowledge about doses of artemether-lumefantrine for adults compared with workers in private dispensaries (P = 0.001). Only 58.0% of respondents were able to state correctly the recommended doses in private dispensaries as compared with 77.0% in public dispensaries. Knowledge about the requirement for a concomitant fatty meal was not significantly different between workers in public and private dispensaries (P = 0.280) or between those working in public dispensaries and pharmacies (P = 0.622). CONCLUSION: Knowledge about the use of artemether lumefantrine was higher among health workers in public dispensaries than in their counterparts from private health care settings. The training organized by the Ministry of Health for workers in public health facilities in Tanzania contributed to such differences. PMID- 22312232 TI - Ensuring safe access to medication for palliative care while preventing prescription drug abuse: innovations for American inner cities, rural areas, and communities overwhelmed by addiction. AB - This article proposes and develops novel components of community-oriented programs for creating and affording access to safe medication dispensing centers in existing retail pharmacies and in permanent or travelling pharmacy clinics that are guarded by assigned or off-duty police officers. Pharmacists at these centers would work with police, medical providers, social workers, hospital administrators, and other professionals in: planning and overseeing the safe storage of controlled substance medications in off-site community safe-deposit boxes; strengthening communication and cooperation with the prescribing medical provider; assisting the prescribing medical provider in patient monitoring (checking the state prescription registry, providing pill counts and urine samples); expanding access to lower-cost, and in some cases, abuse-resistant formulations of controlled substance medications; improving transportation access for underserved patients and caregivers to obtain prescriptions; and integrating community agencies and social networks as resources for patient support and monitoring. Novel components of two related community-oriented programs, which may be hosted outside of safe medication dispensing centers, are also suggested and described: (1) developing medication purchasing cooperatives (ie, to help patients, families, and health institutions afford the costs of medications, including tamper-or abuse-resistant/deterrent drug formulations); and (2) expanding the role of inner-city methadone maintenance treatment programs in palliative care (ie, to provide additional patient monitoring from a second treatment team focusing on narcotics addiction, and potentially, to serve as an untapped source of opioid medication for pain that is less subject to abuse, misuse, or diversion). PMID- 22312233 TI - Causes and consequences of injuries in children in Western Australia. AB - OBJECTIVE: To identify the common causes and consequences of pediatric injury related admission to an Australian children's hospital. METHODS: A retrospective study was conducted at a pediatric teaching hospital. Patients < 18 years of age hospitalized between March 1, 2007 and April 30, 2007 were included. Patient medical records were reviewed if an admission diagnosis was injury related. Data collected included date of birth, gender, date of admission, date of discharge, diagnosis, procedure, and causes and outcomes of the injury. RESULTS: A total of 184 patients were admitted as a result of injury during the study period. Of these, one neonate, six infants, 38 toddlers, 111 children, and 28 teenagers were included in this study. The most common cause of injury-related hospital admission was a fall (n = 109, 59%). Other causes of injury included crushing (8%, n = 15), the spilling of fluids (5.4%, n = 10), and bites (4.3%, n = 8). The most common consequence of an injury for children (43/111, 38.7%) and teenagers (12/28, 43%) was bone fracture. However, head injuries were the most common injury in toddlers (11/38, 29%), infants (5/6, 83.3%), and neonates (1/1, 100%). The radius and/or ulna (36/63, 57%) were the most common bones fractured. The majority (32/37, 86.5%) of patients who suffered head injuries were diagnosed as having a minor injury. CONCLUSION: The main cause of injury-related admission to the hospital for children was a fall, with the most common consequences being fractures and head injuries. PMID- 22312234 TI - Variance estimation using refitted cross-validation in ultrahigh dimensional regression. AB - Variance estimation is a fundamental problem in statistical modelling. In ultrahigh dimensional linear regression where the dimensionality is much larger than the sample size, traditional variance estimation techniques are not applicable. Recent advances in variable selection in ultrahigh dimensional linear regression make this problem accessible. One of the major problems in ultrahigh dimensional regression is the high spurious correlation between the unobserved realized noise and some of the predictors. As a result, the realized noises are actually predicted when extra irrelevant variables are selected, leading to serious underestimate of the level of noise. We propose a two-stage refitted procedure via a data splitting technique, called refitted cross-validation, to attenuate the influence of irrelevant variables with high spurious correlations. Our asymptotic results show that the resulting procedure performs as well as the oracle estimator, which knows in advance the mean regression function. The simulation studies lend further support to our theoretical claims. The naive two stage estimator and the plug-in one-stage estimators using the lasso and smoothly clipped absolute deviation are also studied and compared. Their performances can be improved by the reffitted cross-validation method proposed. PMID- 22312235 TI - Genetic variability and phylogeny of high risk HPV type 16, 18, 31, 33 and 45 L1 gene in Greek women. AB - The present study explores nucleotide variability, phylogeny and association with cervical neoplasia in high risk HPV types 16, 18, 31, 33 and 45 collected from Greek women. Of the 1894 women undergoing routine cervical cytology examination, 160 samples test positive for single infections of HPV type 16 (n = 104), HPV 31 (n = 40), HPV 33 (n = 7), HPV 18 (n = 5), and HPV 45 (n = 4) were typed by microarrays method, amplified by PCR then sequenced and phylogenetically analyzed. For HPV 16, 9 variants with nucleotide variations were included into the study. For HPV 31, 33, 18 and 45, nucleotide variations were identified in 6, 4, 2 and 3 variants, respectively. The Bayesian inference and Maximum Parsimony methods were used in order to construct the phylogenetic trees. When types were analyzed independently HPV 16 (European and non-European) and HPV 18 (African and non-African) formed distinct clades. The genomic characterization of HPV variants will be important for illuminating the geographical relatedness and biological differences and for the determination of their risk. PMID- 22312236 TI - Oral drug delivery systems comprising altered geometric configurations for controlled drug delivery. AB - Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix((r)) multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise((r)), which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix((r)) as well as "release modules assemblage", which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments. PMID- 22312237 TI - Relation between the adsorbed quantity and the immersion enthalpy in catechol aqueous solutions on activated carbons. AB - An activated carbon, Carbochem(TM)-PS230, was modified by chemical and thermal treatment in flow of H(2), in order to evaluate the influence of the activated carbon chemical characteristics in the adsorption of the catechol. The catechol adsorption in aqueous solution was studied along with the effect of the pH solution in the adsorption process of modified activated carbons and the variation of immersion enthalpy of activated carbons in the aqueous solutions of catechol. The interaction solid-solution is characterized by adsorption isotherms analysis, at 298 K and pH 7, 9 and 11 in order to evaluate the adsorption value above and below that of the catechol pK(a). The adsorption capacity of carbons increases when the solution pH decreases. The retained amount increases slightly in the reduced carbon to maximum adsorption pH and diminishes in the oxidized carbon. Similar conclusions are obtained from the immersion enthalpies, whose values increase with the solute quantity retained. In granular activated carbon (CAG), the immersion enthalpies obtained are between 21.5 and 45.7 J.g(-1) for catechol aqueous solutions in a range of 20 at 1500 mg.L(-1). PMID- 22312239 TI - Is Remusatia (araceae) monophyletic? Evidence from three plastid regions. AB - The genus Remusatia (Araceae) includes four species distributed in the tropical and subtropical Old World. The phylogeny of Remusatia was constructed using parsimony and Bayesian analyses of sequence data from three plastid regions (the rbcL gene, the trnL-trnF intergenic spacer, and the rps16 intron). Phylogenetic analyses of the concatenated plastid data suggested that the monophyly of Remusatia was not supported because R. hookeriana did not form a clade with the other three species R. vivipara, R. yunnanensis, and R. pumila. Nevertheless, the topology of the analysis constraining Remusatia to monophyly was congruent with the topology of the unconstrained analysis. The results confirmed the inclusion of the previously separate genus Gonatanthus within Remusatia and disagreed with the current infrageneric classification of the genus. PMID- 22312240 TI - Characterization and comparison of Fumonisin B(1)-protein conjugates by six methods. AB - In order to generate an antibody against a small hapten molecule, the hapten is cross-linked with carrier protein to make it immunogenic. In this study, the hapten (Fumonisin B(1), FB(1)) was coupled to ovalbumin (OVA) and bovine serum albumin (BSA), respectively by a short cross-linker reagent (glutaraldehyde, GA). To develop a technique for detecting the conjugation, the hapten-protein conjugates (FB(1)-OVA and FB(1)-BSA) were characterized thoroughly by ultraviolet (UV) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), respectively. The molecular weights of FB(1) BSA and FB(1)-OVA were 74,355.301 Da and 48,009.212 Da, respectively determined by the method of MALDI-TOF-MS. The molecular coupling ratios were 11 and 5 in FB(1)-BSA and FB(1)-OVA, respectively. In this experiment, MALDI-TOF-MS was selected as the most efficient method to evaluate the cross-linking effect and calculate the molecular coupling ratio. PMID- 22312238 TI - The bone-protective effect of genistein in the animal model of bilateral ovariectomy: roles of phytoestrogens and PTH/PTHR1 against post-menopausal osteoporosis. AB - Genistein, a major phytoestrogen of soy, is considered a potential drug for the prevention and treatment of post-menopausal osteoporosis. Mounting evidence suggested a positive correlation between genistein consumption and bone health both in vivo and in vitro. Earlier studies have revealed that genistein acted as a natural estrogen analogue which activated estrogen receptor and exerted anti osteoporotic effect. However, it remains unclear whether PTH, the most crucial hormone that regulates mineral homeostasis, participates in the process of genistein-mediated bone protection. In the present study, we compared the therapeutic effects between genistein and nilestriol and investigated whether PTH and its specific receptor PTHR1 altered in response to genistein-containing diet in the animal model of ovariectomy. Our results showed that genistein administration significantly improved femoral mechanical properties and alleviates femoral turnover. Genistein at all doses (4.5 mg/kg, 9.0 mg/kg and 18.0 mg/kg per day, respectively) exerted improved bending strength and b-ALP limiting effects than nilestriol in the present study. However, genistein administration did not exert superior effects on bone protection than nilestriol. We also observed circulating PTH restoration in ovariectomized rats receiving genistein at the dose of 18 mg/kg per day. Meanwhile, PTHR1 abnormalities were attenuated in the presence of genistein as confirmed by RT-PCR, Western blot and immunohistochemistry. These findings strongly support the idea that besides serving as an estrogen, genistein could interact with PTH/PTHR1, causing a superior mineral restoring effect than nilestriol on certain circumstance. In conclusion, our study reported for the first time that the anti-osteoporotic effect of genistein is partly PTH/PTHR1-dependent. Genistein might be a potential option in the prevention and treatment of post-menopausal osteoporosis with good tolerance, more clinical benefits and few undesirable side effects. PMID- 22312242 TI - New PCR assays for the identification of Fusarium verticillioides, Fusarium subglutinans, and other species of the Gibberella fujikuroi complex. AB - Fusarium verticillioides and Fusarium subglutinans are important fungal pathogens of maize and other cereals worldwide. In this study, we developed PCR-based protocols for the identification of these pathogens targeting the gaoB gene, which codes for galactose oxidase. The designed primers recognized isolates of F. verticillioides and F. subglutinans that were obtained from maize seeds from several producing regions of Brazil but did not recognize other Fusarium spp. or other fungal genera that were either obtained from fungal collections or isolated from maize seeds. A multiplex PCR protocol was established to simultaneously detect the genomic DNA from F. verticillioides and F. subglutinans. This protocol could detect the DNA from these fungi growing in artificially or naturally infected maize seeds. Another multiplex reaction with a pair of primers developed in this work combined with a pre-existing pair of primers has allowed identifying F. subglutinans, F. konzum, and F. thapsinum. In addition, the identification of F. nygamai was also possible using a combination of two PCR reactions described in this work, and another described in the literature. PMID- 22312241 TI - Bioinformatics tools and novel challenges in long non-coding RNAs (lncRNAs) functional analysis. AB - The advent of next generation sequencing revealed that a fraction of transcribed RNAs (short and long RNAs) is non-coding. Long non-coding RNAs (lncRNAs) have a crucial role in regulating gene expression and in epigenetics (chromatin and histones remodeling). LncRNAs may have different roles: gene activators (signaling), repressors (decoy), cis and trans gene expression regulators (guides) and chromatin modificators (scaffolds) without the need to be mutually exclusive. LncRNAs are also implicated in a number of diseases. The huge amount of inhomogeneous data produced so far poses several bioinformatics challenges spanning from the simple annotation to the more complex functional annotation. In this review, we report and discuss several bioinformatics resources freely available and dealing with the study of lncRNAs. To our knowledge, this is the first review summarizing all the available bioinformatics resources on lncRNAs appeared in the literature after the completion of the human genome project. Therefore, the aim of this review is to provide a little guide for biologists and bioinformaticians looking for dedicated resources, public repositories and other tools for lncRNAs functional analysis. PMID- 22312243 TI - Effect of Byrsonima crassa and phenolic constituents on Helicobacter pylori induced neutrophils oxidative burst. AB - Byrsonima crassa Niedenzu (Malpighiaceae) is used in Brazilian folk medicine for the treatment of diseases related mainly to gastric ulcers. In a previous study, our group described the gastric protective effect of the methanolic extract from the leaves of B. crassa. The present study was carried out to investigate the effects of methanolic extract and its phenolic compounds on the respiratory burst of neutrophils stimulated by H. pylori using a luminol-based chemiluminescence assay as well as their anti-H. pylori activity. The suppressive activity on oxidative burst of H. pylori-stimulated neutrophils was in the order of methyl gallate > (+)-catechin > methanol extract > quercetin 3-O-alpha-l arabinopyranoside > quercetin 3-O-beta-d-galactopyranoside > amentoflavone. Methyl gallate, compound that induced the highest suppressive activity with IC(50) value of 3.4 MUg/mL, did not show anti-H. pylori activity. B. crassa could be considered as a potential source of natural antioxidant in gastric ulcers by attenuating the effects on the damage to gastric mucosa caused by neutrophil generated reactive oxygen species, even when H. pylori displays its evasion mechanisms. PMID- 22312245 TI - Significance of dietary antioxidants for health. AB - Since evidence became available that free radicals were involved in mechanisms for the development of major diseases, including cardiovascular disease and cancer, there has been considerable research into the properties of natural dietary antioxidants. However, it has become clear that dietary antioxidants can only have beneficial effects in vivo by radical scavenging or effects on redox potential if they are present in tissues or bodily fluids at sufficient concentrations. For many dietary components, absorption is limited or metabolism into derivatives reduces the antioxidant capacity. For many dietary phytochemicals, direct antioxidant effects may be less important for health than other effects including effects on cell signalling or gene expression in vivo. PMID- 22312244 TI - Protein kinases and transcription factors activation in response to UV-radiation of skin: implications for carcinogenesis. AB - Solar ultraviolet (UV) radiation is an important environmental factor that leads to immune suppression, inflammation, photoaging, and skin carcinogenesis. Here, we reviewed the specific signal transduction pathways and transcription factors involved in the cellular response to UV-irradiation. Increasing experimental data supporting a role for p38, MAPK, JNK, ERK1/2, and ATM kinases in the response network to UV exposure is discussed. We also reviewed the participation of NF kappaB, AP-1, and NRF2 transcription factors in the control of gene expression after UV-irradiation. In addition, we discussed the promising chemotherapeutic intervention of transcription factors signaling by natural compounds. Finally, we focused on the review of data emerging from the use of DNA microarray technology to determine changes in global gene expression in keratinocytes and melanocytes in response to UV treatment. Efforts to obtain a comprehensive portrait of the transcriptional events regulating photodamage of intact human epidermis after UV exposure reveals the existence of novel factors participating in UV-induced cell death. Progress in understanding the multitude of mechanisms induced by UV irradiation could lead to the potential use of protein kinases and novel proteins as specific targets for the prevention and control of skin cancer. PMID- 22312246 TI - The effect of hydrogen content on ballistic transport behaviors in the Ni-Nb-Zr-H glassy alloys. AB - The electronic transport behaviors of (Ni(0.39)Nb(0.25)Zr(0.35))(100-) (x)H(x) (0 <= x < 23.5) glassy alloys with subnanostructural icosahedral Zr(5)Nb(5)Ni(3) clusters have been studied as a function of hydrogen content. These alloys show semiconducting, electric current-induced voltage (Coulomb) oscillation and ballistic transport behaviors. Coulomb oscillation and ballistic transport occur at hydrogen contents between 6.7 and 13.5 at% and between 13.5 and 21.2 at%, respectively. These results suggest that the localization effect of hydrogen in the clusters plays an important role in various electron transport phenomena. PMID- 22312247 TI - Multi-parametric profiling network based on gene expression and phenotype data: a novel approach to developmental neurotoxicity testing. AB - The establishment of more efficient approaches for developmental neurotoxicity testing (DNT) has been an emerging issue for children's environmental health. Here we describe a systematic approach for DNT using the neuronal differentiation of mouse embryonic stem cells (mESCs) as a model of fetal programming. During embryoid body (EB) formation, mESCs were exposed to 12 chemicals for 24 h and then global gene expression profiling was performed using whole genome microarray analysis. Gene expression signatures for seven kinds of gene sets related to neuronal development and neuronal diseases were selected for further analysis. At the later stages of neuronal cell differentiation from EBs, neuronal phenotypic parameters were determined using a high-content image analyzer. Bayesian network analysis was then performed based on global gene expression and neuronal phenotypic data to generate comprehensive networks with a linkage between early events and later effects. Furthermore, the probability distribution values for the strength of the linkage between parameters in each network was calculated and then used in principal component analysis. The characterization of chemicals according to their neurotoxic potential reveals that the multi-parametric analysis based on phenotype and gene expression profiling during neuronal differentiation of mESCs can provide a useful tool to monitor fetal programming and to predict developmentally neurotoxic compounds. PMID- 22312248 TI - Vinculin motion modes analysis with elastic network model. AB - Vinculin is an important protein for the linkage between adhesion molecules and the actin cytoskeleton. The activation mechanism of vinculin is still controversial. In order to provide useful information for a better understanding of its activation, we analyze the motion mode of vinculin with elastic network model in this work. The results show that, to some extent, the five domains will present structural rigidity in the motion process. The differences between the structure fluctuations of these domains are significant. When vinculin interacted with other partners, the central long alpha-helix of the first domain becomes bent. This bending deformation can weaken the interaction between the first domain and the tail domain. This motion mode of the first domain is in good agreement with the information extracted from some realistic complex structures. With the aid of the anisotropy elastic network mode, we analyze the motion directions of these domains. The fourth domain has a rotational motion. This rotation is favorable for the releasing of the tail domain from the pincer-like clamp, which is formed by the first and the third domain. All these motion modes are an inherent feature of the structure, and these modes mainly depend on the topology character of the structure. PMID- 22312249 TI - Molecular basis of medullary thyroid carcinoma: the role of RET polymorphisms. AB - Medullary thyroid carcinoma is a rare malignant tumor originating in parafollicular C cells. It accounts for 5 to 8% of all thyroid cancers. MTC develops in either sporadic (75%) or hereditary form (25%). Genetic and molecular studies have demonstrated the involvement of the RET proto-oncogene in hereditary MTC and, less often, in its sporadic form. Although a strong genotype-phenotype correlation has been described, wide clinical heterogeneity is observed among families with the same RET mutation or even in carriers of the same kindred. In recent years, several single nucleotide polymorphisms of the RET gene have been described in the general population as well as in patients with MTC. Some studies have reported associations between the presence of polymorphisms and development or progression of MTC. Nonetheless, other studies failed to demonstrate any effect of the RET variants. Differences in the genetic background of distinct populations or methodological approaches have been suggested as potential reasons for the conflicting results. Here, we review current knowledge concerning the molecular pathogenesis of sporadic and hereditary MTC. In particular, we analyze the role of RET polymorphisms in the clinical presentation and prognosis of MTC based on the current literature. PMID- 22312250 TI - Fractionation of whey protein isolate with supercritical carbon dioxide-process modeling and cost estimation. AB - An economical and environmentally friendly whey protein fractionation process was developed using supercritical carbon dioxide (sCO(2)) as an acid to produce enriched fractions of alpha-lactalbumin (alpha-LA) and beta-lactoglobulin (beta LG) from a commercial whey protein isolate (WPI) containing 20% alpha-LA and 55% beta-LG, through selective precipitation of alpha-LA. Pilot-scale experiments were performed around the optimal parameter range (T = 60 to 65 degrees C, P = 8 to 31 MPa, C = 5 to 15% (w/w) WPI) to quantify the recovery rates of the individual proteins and the compositions of both fractions as a function of processing conditions. Mass balances were calculated in a process flow-sheet to design a large-scale, semi-continuous process model using SuperproDesigner(r) software. Total startup and production costs were estimated as a function of processing parameters, product yield and purity. Temperature, T, pressure, P, and concentration, C, showed conflicting effects on equipment costs and the individual precipitation rates of the two proteins, affecting the quantity, quality, and production cost of the fractions considerably. The highest alpha-LA purity, 61%, with 80% alpha-LA recovery in the solid fraction, was obtained at T = 60 degrees C, C = 5% WPI, P = 8.3 MPa, with a production cost of $8.65 per kilogram of WPI treated. The most profitable conditions resulted in 57%-pure alpha-LA, with 71% alpha-LA recovery in the solid fraction and 89% beta-LG recovery in the soluble fraction, and production cost of $5.43 per kilogram of WPI treated at T = 62 degrees C, C = 10% WPI and P = 5.5 MPa. The two fractions are ready-to-use, new food ingredients with a pH of 6.7 and contain no residual acid or chemical contaminants. PMID- 22312251 TI - Determination of phenolic acids and flavonoids in Taraxacum formosanum Kitam by liquid chromatography-tandem mass spectrometry coupled with a post-column derivatization technique. AB - A liquid chromatography-tandem mass spectrometry method (LC-MS/MS) was developed for the determination of phenolic acids and flavonoids in a medicinal Chinese herb Taraxacum formosanum Kitam. Initially, both phenolic acids and flavonoids were extracted with 50% ethanol in a water-bath at 60 degrees C for 3 h and eventually separated into acidic fraction and neutral fraction by using a C(18) cartridge. A total of 29 compounds were separated within 68 min by employing a Gemini C(18) column and a gradient solvent system of 0.1% formic acid and acetonitrile at a flow rate of 1.0 mL/min. Based on the retention behavior as well as absorption and mass spectra, 19 phenolic acids and 10 flavonoids were identified and quantified in T. formosanum, with the former ranging from 14.1 MUg/g to 10,870.4 MUg/g, and the latter from 9.9 MUg/g to 325.8 MUg/g. For further identification of flavonoids, a post-column derivatization method involving shift reagents such as sodium acetate or aluminum chloride was used and the absorption spectral characteristics without or with shift reagents were compared. An internal standard syringic acid was used for quantitation of phenolic acids, whereas (+/-) naringenin was found suitable for quantitation of flavonoids. The developed LC-MS/MS method showed high reproducibility, as evident from the relative standard deviation (RSD) values for intra-day and inter-day variability being 1.0-6.8% and 2.0-7.7% for phenolic acids and 3.7-7.4% and 1.5 8.1% for flavonoids, respectively, and thus may be applied for simultaneous determination of phenolic acids and flavonoids in Chinese herb and nutraceuticals. PMID- 22312252 TI - Chemical composition, starch digestibility and antioxidant capacity of tortilla made with a blend of quality protein maize and black bean. AB - Tortilla and beans are the basic components in the diet of people in the urban and rural areas of Mexico. Quality protein maize is suggested for tortilla preparation because it presents an increase in lysine and tryptophan levels. Beans contain important amounts of dietary fiber. The objective of this study was to prepare tortilla with bean and assesses the chemical composition, starch digestibility and antioxidant capacity using a quality protein maize variety. Tortilla with bean had higher protein, ash, dietary fiber and resistant starch content, and lower digestible starch than control tortilla. The hydrolysis rate (60 to 50%) and the predicted glycemic index (88 to 80) of tortilla decreased with the addition of bean in the blend. Extractable polyphenols and proanthocyanidins were higher in the tortilla with bean than control tortilla. This pattern produced higher antioxidant capacity of tortilla with bean (17.6 MUmol Trolox eq/g) than control tortilla (7.8 MUmol Trolox eq/g). The addition of bean to tortilla modified the starch digestibility and antioxidant characteristics of tortilla, obtaining a product with nutraceutical characteristics. PMID- 22312253 TI - Photocatalytic degradation of p-cresol by zinc oxide under UV irradiation. AB - Photocatalytic degradation of p-cresol was carried out using ZnO under UV irradiation. The amount of photocatalyst, concentration of p-cresol and pH were studied as variables. The residual concentration and mineralization of p-cresol was monitored using a UV-visible spectrophotometer and total organic carbon (TOC) analyzer, respectively. The intermediates were detected by ultra high pressure liquid chromatography (UPLC). The highest photodegradation of p-cresol was observed at 2.5 g/L of ZnO and 100 ppm of p-cresol. P-cresol photocatalytic degradation was favorable in the pH range of 6-9. The detected intermediates were 4-hydroxy-benzaldehyde and 4-methyl-1,2-benzodiol. TOC studies show that 93% of total organic carbon was removed from solution during irradiation time. Reusability shows no significant reduction in photocatalytic performance in photodegrading p-cresol. PMID- 22312255 TI - Wound healing activity of Elaeis guineensis leaf extract ointment. AB - Elaeis guineensis of the Arecaceae family is widely used in the traditional medicine of societies in West Africa for treating various ailments. To validate the ethnotherapeutic claims of the plant in skin diseases, wound healing activity was studied. The results showed that E. guineensis leaf extract had potent wound healing capacity as evident from the better wound closure (P < 0.05), improved tissue regeneration at the wound site, and supporting histopathological parameters pertaining to wound healing. Matrix metalloproteinases expression correlated well with the results thus confirming efficacy of E. guineensis in the treatment of the wound. E. guineensis accelerated wound healing in rats, thus supporting its traditional use. The result of this study suggested that, used efficiently, oil palm leaf extract is a renewable resource with wound healing properties. PMID- 22312254 TI - Human gene control by vital oncogenes: revisiting a theoretical model and its implications for targeted cancer therapy. AB - An important assumption of our current understanding of the mechanisms of carcinogenesis has been the belief that clarification of the cancer process would inevitably reveal some of the crucial mechanisms of normal human gene regulation. Since the momentous work of Bishop and Varmus, both the molecular and the biochemical processes underlying the events in the development of cancer have become increasingly clear. The identification of cellular signaling pathways and the role of protein kinases in the events leading to gene activation have been critical to our understanding not only of normal cellular gene control mechanisms, but also have clarified some of the important molecular and biochemical events occurring within a cancer cell. We now know that oncogenes are dysfunctional proto-oncogenes and that dysfunctional tumor suppressor genes contribute to the cancer process. Furthermore, Weinstein and others have hypothesized the phenomenon of oncogene addiction as a distinct characteristic of the malignant cell. It can be assumed that cancer cells, indeed, become dependent on such vital oncogenes. The products of these vital oncogenes, such as c-myc, may well be the Achilles heel by which targeted molecular therapy may lead to truly personalized cancer therapy. The remaining problem is the need to introduce relevant molecular diagnostic tests such as genome microarray analysis and proteomic methods, especially protein kinase identification arrays, for each individual patient. Genome wide association studies on cancers with gene analysis of single nucleotide and other mutations in functional proto-oncogenes will, hopefully, identify dysfunctional proto-oncogenes and allow the development of more specific targeted drugs directed against the protein products of these vital oncogenes. In 1984 Willis proposed a molecular and biochemical model for eukaryotic gene regulation suggesting how proto-oncogenes might function within the normal cell. That model predicted the existence of vital oncogenes and can now be used to hypothesize the biochemical and molecular mechanisms that drive the processes leading to disruption of the gene regulatory machinery, resulting in the transformation of normal cells into cancer. PMID- 22312256 TI - Acidic pretreatment of wheat straw in decanol for the production of surfactant, lignin and glucose. AB - Wheat straw is an abundant residue of agriculture which is increasingly being considered as feedstock for the production of fuels, energy and chemicals. The acidic decanol-based pre-treatment of wheat straw has been investigated in this work. Wheat straw hemicellulose has been efficiently converted during a single step operation into decyl pentoside surfactants and the remaining material has been preserved keeping all its promises as potential feedstock for fuels or value added platform chemicals such as hydroxymethylfurfural (HMF). The enzymatic digestibility of the cellulose contained in the straw residue has been evaluated and the lignin prepared from the material characterized. Wheat-based surfactants thus obtained have exhibited superior surface properties compared to fossil-based polyethoxylates decyl alcohol or alkyl oligoglucosides, some of which are largely used surfactants. In view of the growing importance of renewable resource-based molecules in the chemical industry, this approach may open a new avenue for the conversion of wheat straw into various chemicals. PMID- 22312257 TI - Expression, immobilization and enzymatic properties of glutamate decarboxylase fused to a cellulose-binding domain. AB - Escherichia coli-derived glutamate decarboxylase (GAD), an enzyme that catalyzes the conversion of glutamic acid to gamma-aminobutyric acid (GABA), was fused to the cellulose-binding domain (CBD) and a linker of Trichoderma harzianum endoglucanase II. To prevent proteolysis of the fusion protein, the native linker was replaced with a S(3)N(10) peptide known to be completely resistant to E. coli endopeptidase. The CBD-GAD expressed in E. coli was successfully immobilized on Avicel, a crystalline cellulose, with binding capacity of 33 +/- 2 nmol(CBD GAD)/g(Avicel) and the immobilized enzymes retained 60% of their initial activities after 10 uses. The results of this report provide a feasible alternative to produce GABA using immobilized GAD through fusion to CBD. PMID- 22312258 TI - Potentiation of anticancer drugs: effects of pentoxifylline on neoplastic cells. AB - The drug efflux activity of P-glycoprotein (P-gp, a product of the mdr1 gene, ABCB1 member of ABC transporter family) represents a mechanism by which tumor cells escape death induced by chemotherapeutics. In this study, we investigated the mechanisms involved in the effects of pentoxifylline (PTX) on P-gp-mediated multidrug resistance (MDR) in mouse leukemia L1210/VCR cells. Parental sensitive mouse leukemia cells L1210, and multidrug-resistant cells, L1210/VCR, which are characterized by the overexpression of P-gp, were used as experimental models. The cells were exposed to 100 MUmol/L PTX in the presence or absence of 1.2 MUmol/L vincristine (VCR). Western blot analysis indicated a downregulation of P gp protein expression when multidrug-resistant L1210/VCR cells were exposed to PTX. The effects of PTX on the sensitization of L1210/VCR cells to VCR correlate with the stimulation of apoptosis detected by Annexin V/propidium iodide apoptosis necrosis kit and proteolytic activation of both caspase-3 and caspase-9 monitored by Western blot analysis. Higher release of matrix metalloproteinases (MMPs), especially MMP-2, which could be attenuated by PTX, was found in L1210/VCR than in L1210 cells by gelatin zymography in electrophoretic gel. Exposure of resistant cells to PTX increased the content of phosphorylated Akt kinase. In contrast, the presence of VCR eliminated the effects of PTX on Akt kinase phosphorylation. Taken together, we conclude that PTX induces the sensitization of multidrug-resistant cells to VCR via downregulation of P-gp, stimulation of apoptosis and reduction of MMPs released from drug-resistant L1210/VCR cells. These facts bring new insights into the mechanisms of PTX action on cancer cells. PMID- 22312259 TI - Assessment of genetic diversity of Bermudagrass (Cynodon dactylon) using ISSR markers. AB - Bermudagrass (Cynodon spp.) is a major turfgrass for home lawns, public parks, golf courses and sport fields and is known to have originated in the Middle East. Morphological and physiological characteristics are not sufficient to differentiate some bermudagrass genotypes because the differences between them are often subtle and subjected to environmental influences. In this study, twenty seven bermudagrass accessions and introductions, mostly from different parts of Iran, were assayed by inter-simple sequence repeat (ISSR) markers to differentiate and explore their genetic relationships. Fourteen ISSR primers amplified 389 fragments of which 313 (80.5%) were polymorphic. The average polymorphism information content (PIC) was 0.328, which shows that the majority of primers are informative. Cluster analysis using the un-weighted paired group method with arithmetic average (UPGMA) method and Jaccard's similarity coefficient (r = 0.828) grouped the accessions into six main clusters according to some degree to geographical origin, their chromosome number and some morphological characteristics. It can be concluded that there exists a wide genetic base of bermudograss in Iran and that ISSR markers are effective in determining genetic diversity and relationships among them. PMID- 22312260 TI - Involvement of nitrogen on flavonoids, glutathione, anthocyanin, ascorbic acid and antioxidant activities of Malaysian medicinal plant Labisia pumila Blume (Kacip Fatimah). AB - A split plot 3 by 4 experiment was designed to characterize the relationship between production of gluthatione (GSH), oxidized gluthatione (GSSG), total flavonoid, anthocyanin, ascorbic acid and antioxidant activities (FRAP and DPPH) in three varieties of Labisia pumila Blume, namely the varieties alata, pumila and lanceolata, under four levels of nitrogen fertilization (0, 90, 180 and 270 kg N/ha) for 15 weeks. The treatment effects were solely contributed by nitrogen application; there was neither varietal nor interaction effects observed. As the nitrogen levels decreased from 270 to 0 kg N/ha, the production of GSH and GSSG, anthocyanin, total flavonoid and ascorbic acid increased steadily. At the highest nitrogen treatment level, L. pumila exhibited significantly lower antioxidant activities (DPPH and FRAP) than those exposed to limited nitrogen growing conditions. Significant positive correlation was obtained between antioxidant activities (DPPH and FRAP), total flavonoid, GSH, GSSG, anthocyanin and ascorbic acid suggesting that an increase in the antioxidative activities in L. pumila under low nitrogen fertilization could be attributed to higher contents of these compounds. From this observation, it could be concluded that in order to avoid negative effects on the quality of L. pumila, it is advisable to avoid excessive application of nitrogen fertilizer when cultivating the herb for its medicinal use. PMID- 22312261 TI - In vitro antioxidant, anticoagulant and antimicrobial activity and in inhibition of cancer cell proliferation by xylan extracted from corn cobs. AB - Xylan is one of most abundant polymer after cellulose. However, its potential has yet to be completely recognized. Corn cobs contain a considerable reservoir of xylan. The aim of this work was to study some of the biological activities of xylan obtained from corn cobs after alkaline extraction enhanced by ultrasonication. Physical chemistry and infrared analyses showed 130 kDa heteroxylan containing mainly xylose:arabinose: galactose:glucose (5.0:1.5:2.0:1.2). Xylan obtained exhibited total antioxidant activity corresponding to 48.5 mg of ascorbic acid equivalent/g of xylan. Furthermore, xylan displayed high ferric chelating activity (70%) at 2 mg/mL. Xylan also showed anticoagulant activity in aPTT test. In antimicrobial assay, the polysaccharide significantly inhibited bacterial growth of Klebsiella pneumoniae. In a test with normal and tumor human cells, after 72 h, only HeLa tumor cell proliferation was inhibited (p < 0.05) in a dose-dependent manner by xylan, reaching saturation at around 2 mg/mL, whereas 3T3 normal cell proliferation was not affected. The results suggest that it has potential clinical applications as antioxidant, anticoagulant, antimicrobial and antiproliferative compounds. PMID- 22312262 TI - Adaptation of high-throughput screening in drug discovery-toxicological screening tests. AB - High-throughput screening (HTS) is one of the newest techniques used in drug design and may be applied in biological and chemical sciences. This method, due to utilization of robots, detectors and software that regulate the whole process, enables a series of analyses of chemical compounds to be conducted in a short time and the affinity of biological structures which is often related to toxicity to be defined. Since 2008 we have implemented the automation of this technique and as a consequence, the possibility to examine 100,000 compounds per day. The HTS method is more frequently utilized in conjunction with analytical techniques such as NMR or coupled methods e.g., LC-MS/MS. Series of studies enable the establishment of the rate of affinity for targets or the level of toxicity. Moreover, researches are conducted concerning conjugation of nanoparticles with drugs and the determination of the toxicity of such structures. For these purposes there are frequently used cell lines. Due to the miniaturization of all systems, it is possible to examine the compound's toxicity having only 1-3 mg of this compound. Determination of cytotoxicity in this way leads to a significant decrease in the expenditure and to a reduction in the length of the study. PMID- 22312263 TI - Force measurement enabling precise analysis by dynamic force spectroscopy. AB - Dynamic force spectroscopy (DFS) makes it possible to investigate specific interactions between two molecules such as ligand-receptor pairs at the single molecule level. In the DFS method based on the Bell-Evans model, the unbinding force applied to a molecular bond is increased at a constant rate, and the force required to rupture the molecular bond is measured. By analyzing the relationship between the modal rupture force and the logarithm of the loading rate, microscopic potential barrier landscapes and the lifetimes of bonds can be obtained. However, the results obtained, for example, in the case of streptavidin/biotin complexes, have differed among previous studies and some results have been inconsistent with theoretical predictions. In this study, using an atomic force microscopy technique that enables the precise analysis of molecular interactions on the basis of DFS, we investigated the effect of the sampling rate on DFS analysis. The shape of rupture force histograms, for example, was significantly deformed at a sampling rate of 1 kHz in comparison with that of histograms obtained at 100 kHz, indicating the fundamental importance of ensuring suitable experimental conditions for further advances in the DFS method. PMID- 22312264 TI - Fungus-mediated green synthesis of silver nanoparticles using Aspergillus terreus. AB - The biosynthesis of nanoparticles has received increasing attention due to the growing need to develop safe, cost-effective and environmentally friendly technologies for nano-materials synthesis. In this report, silver nanoparticles (AgNPs) were synthesized using a reduction of aqueous Ag(+) ion with the culture supernatants of Aspergillus terreus. The reaction occurred at ambient temperature and in a few hours. The bioreduction of AgNPs was monitored by ultraviolet visible spectroscopy, and the AgNPs obtained were characterized by transmission electron microscopy and X-ray diffraction. The synthesized AgNPs were polydispersed spherical particles ranging in size from 1 to 20 nm and stabilized in the solution. Reduced nicotinamide adenine dinucleotide (NADH) was found to be an important reducing agent for the biosynthesis, and the formation of AgNPs might be an enzyme-mediated extracellular reaction process. Furthermore, the antimicrobial potential of AgNPs was systematically evaluated. The synthesized AgNPs could efficiently inhibit various pathogenic organisms, including bacteria and fungi. The current research opens a new avenue for the green synthesis of nano-materials. PMID- 22312265 TI - Non coding RNAs and viruses in the framework of the phylogeny of the genes, epigenesis and heredity. AB - The origin of genes is one of the most enigmatic events in the origin of life. It has been suggested that noncoding (nc) RNA was probably a precursor in the formation of the first polypeptide, and also at the origin of the first manifestation of life and genes. ncRNAs are also becoming central for understanding gene expression and silencing. Indeed, before the discovery of ncRNAs, proteins were viewed as the major molecules in the regulation of gene expression and gene silencing; however, recent findings suggest that ncRNA also plays an important role in gene expression. Reverse transcription of RNA viruses and their integration into the genome of eukaryotes and also their relationship with the ncRNA suggest that their origin is basal in genome evolution, and also probably constitute the first mechanism of gene regulation. I am to review the different roles of ncRNAs in the framework of gene evolution, as well as the importance of ncRNAs and viruses in the epigenesis and in the non-Mendelian model of heredity and evolution. PMID- 22312266 TI - Occurrence and biodegradation of nonylphenol in the environment. AB - Nonylphenol (NP) is an ultimate degradation product of nonylphenol polyethoxylates (NPE) that is primarily used in cleaning and industrial processes. Its widespread use has led to the wide existence of NP in various environmental matrices, such as water, sediment, air and soil. NP can be decreased by biodegradation through the action of microorganisms under aerobic or anaerobic conditions. Half-lives of biodegradation ranged from a few days to almost one hundred days. The degradation rate for NP was influenced by temperature, pH and additions of yeast extracts, surfactants, aluminum sulfate, acetate, pyruvate, lactate, manganese dioxide, ferric chloride, sodium chloride, hydrogen peroxide, heavy metals, and phthalic acid esters. Although NP is present at low concentrations in the environment, as an endocrine disruptor the risks of long-term exposure to low concentrations remain largely unknown. This paper reviews the occurrence of NP in the environment and its aerobic and anaerobic biodegradation in natural environments and sewage treatment plants, which is essential for assessing the potential risk associated with low level exposure to NP and other endocrine disruptors. PMID- 22312267 TI - Molecular cloning and functional characterization of Tibetan Porcine STING. AB - Tibetan pig is well known for its strong disease resistance. However, little is known about the molecular basis of its strong resistance to disease. Stimulator of interferon (IFN) genes (STING), also known as MPYS/MITA/ERIS/TMEM173, is an adaptor that functions downstream of RIG-I and MAVS and upstream of TBK1 and plays a critical role in type I IFN induction. Here we report the first cloning and characterization of STING gene from Tibetan pig. The entire open reading frame (ORF) of the Tibetan porcine STING is 1137 bp, with a higher degree of sequence similarity with Landrace pig (98%) and cattle (88%) than with chimpanzee (84%), human (83%) or mouse (77%). The predicted protein is composed of 378 amino acids and has 4 putative transmembrane domains. Real-time quantitative PCR analysis indicated that Tibetan pig STING mRNA was most abundant in the lung and heart. Overexpression of Tibetan porcine STING led to upregulation of IFN-beta and IFN-stimulated gene 15 (ISG15) in porcine jejunal epithelial cell line IPEC J2 cells. This is the first study investigating the biological role of STING in intestinal epithelial cells, which lays a foundation for the further study of STING in intestinal innate immunity. PMID- 22312268 TI - Biodegradable nanoparticles of mPEG-PLGA-PLL triblock copolymers as novel non viral vectors for improving siRNA delivery and gene silencing. AB - Degradation of mRNA by RNA interference is one of the most powerful and specific mechanisms for gene silencing. However, insufficient cellular uptake and poor stability have limited its usefulness. Here, we report efficient delivery of siRNA via the use of biodegradable nanoparticles (NPs) made from monomethoxypoly(ethylene glycol)-poly(lactic-co-glycolic acid)-poly-l-lysine (mPEG-PLGA-PLL) triblock copolymers. Various physicochemical properties of mPEG PLGA-PLL NPs, including morphology, size, surface charge, siRNA encapsulation efficiency, and in vitro release profile of siRNA from NPs, were characterized by scanning electron microscope, particle size and zeta potential analyzer, and high performance liquid chromatography. The levels of siRNA uptake and targeted gene inhibition were detected in human lung cancer SPC-A1-GFP cells stably expressing green fluorescent protein. Examination of the cultured SPC-A1-GFP cells with fluorescent microscope and flow cytometry showed NPs loading Cy3-labeled siRNA had much higher intracellular siRNA delivery efficiencies than siRNA alone and Lipofectamine-siRNA complexes. The gene silencing efficiency of mPEG-PLGA-PLL NPs was higher than that of commercially available transfecting agent Lipofectamine while showing no cytotoxicity. Thus, the current study demonstrates that biodegradable NPs of mPEG-PLGA-PLL triblock copolymers can be potentially applied as novel non-viral vectors for improving siRNA delivery and gene silencing. PMID- 22312269 TI - A set of novel microsatellite markers developed for Luculia yunnanensis (Rubiaceae), an endangered plant endemic to Yunnan, China. AB - The genus Luculia Sweet contains about five species of small trees or shrubs and is a member of the family Rubiaceae (tribe Cinchoneae). Luculia yunnanensis is an endangered ornamental shrub endemic to southwest China. Only two natural populations of L. yunnanensis exist in the wild according to our field investigation. It can be inferred that L. yunnanensis is facing a very high risk of extinction in the wild and an urgent conservation strategy is required. By using a modified biotin-sterptavidin capture method, 24 primer sets were identified in two wild populations. Of these primers, 11 displayed polymorphisms and 13 were monomorphic. The number of alleles per locus ranged from two to four, values for observed and expected heterozygosities ranged from 0.000 to 0.833 and from 0.431 to 0.771, with averages of 0.389 and 0.614, respectively. These markers will be useful for further investigation of conservation of resources, selecting parental types in cross-breeding, evolution of this species at the molecular level and related research in Luculia species. PMID- 22312270 TI - A chitosan induced 9-lipoxygenase in Adelostemma gracillimum seedlings. AB - Oxylipins generated by the lipoxygenase (LOX) pathway play an important role in plant defense against biotic and abiotic stress. In chitosan-treated Adelostemma gracillimum seedlings, obvious accumulation of 9-LOX-derived oxylipins, namely 9,10,11-trihydroxy-12-octadecenoic acid, was detected. Using degenerate primers, a LOX-specific fragment putatively encoding LOX was obtained by RT-PCR, and a 2.9 kb full-length cDNA named AgLOX1 was isolated by RACE from chitosan-induced A. gracillimum seedlings. Genomic Southern analysis implied that there was only one copy of AgLOX1 in the A. gracillimum genome. AgLOX1 was expressed in Escherichia coli and the recombinant protein was partially purified. The enzyme converted linoleic and linolenic acids almost exclusively to their 9-hydroperoxides. AgLOX1 encoded a 9-lipoxygenase. Northern blot analysis indicated that chitosan-induced AgLOX1 transcript accumulation peaked at 8 h after initiation of treatment, whereas trihydroxy derivatives accumulation was highest at 24 h after elicitation. Results showed that chitosan-induced AgLOX1 encoded a 9-lipoxygenase potentially involved in the defense response through 9-LOX pathway leading to biosynthesis of antimicrobial compounds in A. gracillimum seedlings. PMID- 22312271 TI - Development of novel microsatellite markers in the Omei treefrog (Rhacophorus omeimontis). AB - Eleven novel microsatellite markers were developed and characterized for the Omei treefrog (Rhacophorus omeimontis) using the fast isolation by AFLP of sequences containing repeats method. Polymorphism of each locus was tested in 24 individuals from two wild populations. The number of alleles per locus ranged from 4 to 15, the average observed and expected heterozygosity per locus ranged from 0.250 to 0.839 and from 0.562 to 0.914, respectively. Two of the 11 microsatellite loci showed significant deviations from Hardy-Weinberg equilibrium. Two locus pairs showed significant linkage disequilibrium. Neither evidence of scoring error due to stuttering nor evidence of large allele dropout was found at all of the 11 loci, but evidence of null alleles was indicated at two loci because of general excess of homozygotes for most allele size classes. These polymorphic loci will be useful markers in studying mate choice of the Omei treefrog. PMID- 22312273 TI - Nutraceutical approach for preventing obesity-related colorectal and liver carcinogenesis. AB - Obesity and its related metabolic abnormalities, including insulin resistance, alterations in the insulin-like growth factor-1 (IGF-1)/IGF-1 receptor (IGF-1R) axis, and the state of chronic inflammation, increase the risk of colorectal cancer (CRC) and hepatocellular carcinoma (HCC). However, these findings also indicate that the metabolic disorders caused by obesity might be effective targets to prevent the development of CRC and HCC in obese individuals. Green tea catechins (GTCs) possess anticancer and chemopreventive properties against cancer in various organs, including the colorectum and liver. GTCs have also been known to exert anti-obesity, antidiabetic, and anti-inflammatory effects, indicating that GTCs might be useful for the prevention of obesity-associated colorectal and liver carcinogenesis. Further, branched-chain amino acids (BCAA), which improve protein malnutrition and prevent progressive hepatic failure in patients with chronic liver diseases, might be also effective for the suppression of obesity related carcinogenesis because oral supplementation with BCAA reduces the risk of HCC in obese cirrhotic patients. BCAA shows these beneficial effects because they can improve insulin resistance. Here, we review the detailed relationship between metabolic abnormalities and the development of CRC and HCC. We also review evidence, especially that based on our basic and clinical research using GTCs and BCAA, which indicates that targeting metabolic abnormalities by either pharmaceutical or nutritional intervention may be an effective strategy to prevent the development of CRC and HCC in obese individuals. PMID- 22312272 TI - Non-coding RNAs in retinal development. AB - Retinal development is dependent on an accurately functioning network of transcriptional and translational regulators. Among the diverse classes of molecules involved, non-coding RNAs (ncRNAs) play a significant role. Members of this family are present in the cell as transcripts, but are not translated into proteins. MicroRNAs (miRNAs) are small ncRNAs that act as post-transcriptional regulators. During the last decade, they have been implicated in a variety of biological processes, including the development of the nervous system. On the other hand, long-ncRNAs (lncRNAs) represent a different class of ncRNAs that act mainly through processes involving chromatin remodeling and epigenetic mechanisms. The visual system is a prominent model to investigate the molecular mechanisms underlying neurogenesis or circuit formation and function, including the differentiation of retinal progenitor cells to generate the seven principal cell classes in the retina, pathfinding decisions of retinal ganglion cell axons in order to establish the correct connectivity from the eye to the brain proper, and activity-dependent mechanisms for the functionality of visual circuits. Recent findings have associated ncRNAs in several of these processes and uncovered a new level of complexity for the existing regulatory mechanisms. This review summarizes and highlights the impact of ncRNAs during the development of the vertebrate visual system, with a specific focus on the role of miRNAs and a synopsis regarding recent findings on lncRNAs in the retina. PMID- 22312274 TI - Surface photochemistry: 3,3'-dialkylthia and selenocarbocyanine dyes adsorbed onto microcrystalline cellulose. AB - In this work, thia and selenocarbocyanines with n-alkyl chains of different length, namely with methyl, ethyl, propyl, hexyl and decyl substituents, were studied in homogeneous and heterogeneous media for comparison purposes. For both carbocyanine dyes adsorbed onto microcrystalline cellulose, a remarkable increase in the fluorescence quantum yields and lifetimes were detected, when compared with solution. Contrary to the solution behaviour, where the increase in the n alkyl chains length increases to a certain extent the fluorescence emission Phi(F) and tau(F), on powdered solid samples a decrease of Phi(F) and tau(F) was observed. The use of an integrating sphere enabled us to obtain absolute Phi(F)'s for all the powdered samples. The main difference for liquid homogeneous samples is that the increase of the alkyl chain strongly decreases the Phi(F) values, both for thiacarbocyanines and selenocarbocyanines. A lifetime distribution analysis for the fluorescence of these dyes adsorbed onto microcrystalline cellulose, evidenced location on the ordered and crystalline part of the substrate, as well as on the more disordered region where the lifetime is smaller. The increase of the n-alkyl chains length decreases the photoisomer emission for the dyes adsorbed onto microcrystalline cellulose, as detected for high fluences of the laser excitation, for most samples. PMID- 22312275 TI - A new strategy for identification of highly conserved microRNAs in non-model insect, Spodoptera litura. AB - The indigenous small non-coding RNAs, known as microRNAs (miRNAs), are important regulators of gene expression and many of them are evolutionarily conserved. Whether stem-loop RT-PCR, as a sensitive method, could be utilized to clone conserved miRNAs from non-model insects lacks information. Here, three miRNAs, sli-miR-14, sli-miR-2a and sli-bantam, were cloned from Spodoptera litura by stem loop RT-PCR. Two groups of primers were designed, and one of them performed especially well and proved stable. The sequences of two highly conserved miRNAs, sli-miR-14 and sli-miR-2a were identical to those in Drosophila melanogaster. To validate the reliability of this strategy, pre-miR-14 and pre-miR-2a in S. litura as representatives were given as well; this shared high homology with those in D. melanogaster and Bombyx mori, and both mature sequences of sli-miR-14 and sli-miR 2a in their precursors shared 100% identity to the results shown by stem-loop RT PCR. Moreover, expression patterns of these miRNAs were investigated by real-time quantitative PCR. Sli-miR-14 and sli-miR-2a could be detected successfully and their expression patterns showed similar characteristics with those in model insects, further suggesting stem-loop RT-PCR technology can be used for identification of highly conserved miRNAs in non-model insects. These results provide a simplified and efficient strategy for studying the structure and function of highly conserved miRNAs, especially some critical miRNAs in non-model insects. PMID- 22312276 TI - Polyphenol content and modulatory activities of some tropical dietary plant extracts on the oxidant activities of neutrophils and myeloperoxidase. AB - Young leaves of Manihot esculenta Crantz (Euphorbiaceae), Abelmoschus esculentus (Malvaceae), Hibiscus acetosella (Malvaceae) and Pteridium aquilinum (Dennstaedtiaceae) are currently consumed as green vegetables by peoples in sub Saharan Africa, Latin America, Asia and their migrants living in Western Europe. Sub-Saharan peoples use Manihot, Abelmoschus and Hibiscus also in the folk medicine to alleviate fever and pain, in the treatment of conjunctivitis, rheumatism, hemorrhoid, abscesses, ... The present study investigates the effects of aqueous extracts of those plants on the production of reactive oxygen species (ROS) and the release of myeloperoxidase (MPO) by equine neutrophils activated with phorbol 12-myristate 13-acetate (PMA). The ROS production was measured by lucigenin-enhanced chemiluminescence (CL), and the release of total MPO by an ELISA method. The study also investigates the effect of the extracts on the activity of MPO by studying its nitration activity on tyrosine and by using a new technique called SIEFED (Specific Immunological Extraction Followed by Enzymatic Detection) that allows studying the direct interaction of compounds with the enzyme. In all experiments, the aqueous extracts of the plants developed concentration-dependent inhibitory effects. A moderate heat treatment did not significantly modify the inhibitory capacity of the extracts in comparison to not heated ones. Total polyphenol and flavonoid contents were determined with an HPLC UV/DAD analysis and a spectroscopic method using Folin-Ciocalteu reagent. Some polyphenols with well-known antioxidant activities (caffeic acid, chlorogenic acid, hyperoside, rosmarinic acid and rutin) were found in the extracts and may partly explain the inhibitory activities observed. The role of those dietary and medicinal plants in the treatment of ROS-dependent inflammatory diseases could have new considerations for health. PMID- 22312277 TI - Antiproliferative and apoptotic effects triggered by Grape Seed Extract (GSE) versus epigallocatechin and procyanidins on colon cancer cell lines. AB - Grape seed extract has been proven to exert anticancer effects on different tumors. These effects are mainly ascribed to catechin and procyanidin content. Analytical studies demonstrated that grape seed extract composition is complex and it is likely other components could exert biological activities. Using cell count and flow cytometry assays, we evaluated the cytostatic and apoptotic effects produced by three different grape seed extracts from Italia, Palieri and Red Globe cultivars, on Caco2 and HCT-8 colon cancer cells. These effects were compared to those induced by epigallocatechin and procyanidins, alone or in association, on the same cell lines. All the extracts induced growth inhibition and apoptosis in Caco2 and HCT-8 cells, along the intrinsic apoptotic pathway. On both cell lines, growth inhibition induced by Italia and Palieri grape seed extracts was significantly higher than that it has been recorded with epigallocatechin, procyanidins and their association. In Caco2 cells, the extract from Red Globe cultivar was less effective in inducing growth inhibition than procyanidins alone and in association with epigallocatechin, whereas, in HCT-8 cells, only the association of epigallocatechin and procyanidins triggers a significant proliferation decrease. On both cell lines, apoptosis induced by Italia, Palieri and Red Globe grape seed extracts was considerably higher than has been recorded with epigallocatechin, procyanidins and their association. These data support the hypothesis by which other compounds, present in the grape seed extracts, are likely to enhance the anticancer effects. PMID- 22312278 TI - Use of Linear Free Energy Relationships (LFERs) to elucidate the mechanisms of reaction of a gamma-methyl-beta-alkynyl and an ortho-substituted aryl chloroformate ester. AB - The specific rates of solvolysis of 2-butyn-1-yl-chloroformate (1) and 2 methoxyphenyl chloroformate (2) are studied at 25.0 degrees C in a series of binary aqueousorganic mixtures. The rates of reaction obtained are then analyzed using the extended Grunwald-Winstein (G-W) equation and the results are compared to previously published G-W analyses for phenyl chloroformate (3), propargyl chloroformate (4), p-methoxyphenyl choroformate (5), and p-nitrophenyl chloroformate (6). For 1, the results indicate that dual side-by-side addition elimination and ionization pathways are occurring in some highly ionizing solvents due to the presence of the electron-donating gamma-methyl group. For 2, the analyses indicate that the dominant mechanism is a bimolecular one where the formation of a tetrahedral intermediate is rate-determining. PMID- 22312279 TI - Probing kinetic mechanisms of protein function and folding with time-resolved natural and magnetic chiroptical spectroscopies. AB - Recent and ongoing developments in time-resolved spectroscopy have made it possible to monitor circular dichroism, magnetic circular dichroism, optical rotatory dispersion, and magnetic optical rotatory dispersion with nanosecond time resolution. These techniques have been applied to determine structural changes associated with the function of several proteins as well as to determine the nature of early events in protein folding. These studies have required new approaches in triggering protein reactions as well as the development of time resolved techniques for polarization spectroscopies with sufficient time resolution and sensitivity to probe protein structural changes. PMID- 22312280 TI - Effects of acidic polysaccharides from gastrodia rhizome on systolic blood pressure and serum lipid concentrations in spontaneously hypertensive rats fed a high-fat diet. AB - The effects of acidic polysaccharides purified from Gastrodia rhizome on blood pressure and serum lipid levels in spontaneously hypertensive rats (SHR) fed a high-fat diet were investigated. Acidic polysaccharides were purified from crude polysaccharides by DEAE-Sepharose CL-6B. Thirty-six male SHR were randomly divided into three groups: Gastrodia rhizome crude polysaccharide (A), acidic polysaccharide (B) groups, and a control group (C). A 5-week oral administration of all treatment groups was performed daily in 3- to 8-week-old SHRs with a dose of 6 mg/kg of body weight/day. After 5 weeks of treatment, total cholesterol in the acidic polysaccharide group, at 69.7 +/- 10.6 mg/dL, was lower than in the crude polysaccharide group (75.0 +/- 6.0 mg/dL) and the control group (89.2 +/- 7.4 mg/dL). In addition, triglyceride and low-density lipoprotein cholesterol levels in the acidic polysaccharide group were lower than in the crude polysaccharide and control groups. The atherogenic index of the acidic polysaccharide group was 46.3% lower than in the control group. Initial blood pressure after the initial three weeks on the high-fat diet averaged 195.9 +/- 3.3 mmHg among all rats. Compared with the initial blood pressure, the final blood pressure in the control group was increased by 22.8 mmHg, whereas it decreased in the acidic polysaccharide group by 14.9 mmHg. These results indicate that acidic polysaccharides from Gastrodia rhizome reduce hypertension and improve serum lipid levels. PMID- 22312281 TI - Molecular modeling study of chiral separation and recognition mechanism of beta adrenergic antagonists by capillary electrophoresis. AB - Chiral separations of five beta-adrenergic antagonists (propranolol, esmolol, atenolol, metoprolol, and bisoprolol) were studied by capillary electrophoresis using six cyclodextrins (CDs) as the chiral selectors. Carboxymethylated-beta cyclodextrin (CM-beta-CD) exhibited a higher enantioselectivity power compared to the other tested CDs. The influences of the concentration of CM-beta-CD, buffer pH, buffer concentration, temperature, and applied voltage were investigated. The good chiral separation of five beta-adrenergic antagonists was achieved using 50 mM Tris buffer at pH 4.0 containing 8 mM CM-beta-CD with an applied voltage of 24 kV at 20 degrees C. In order to understand possible chiral recognition mechanisms of these racemates with CM-beta-CD, host-guest binding procedures of CM-beta-CD and these racemates were studied using the molecular docking software Autodock. The binding free energy was calculated using the Autodock semi empirical binding free energy function. The results showed that the phenyl or naphthyl ring inserted in the hydrophobic cavity of CM-beta-CD and the side chain was found to point out of the cyclodextrin rim. Hydrogen bonding between CM-beta CD and these racemates played an important role in the process of enantionseparation and a model of the hydrogen bonding interaction positions was constructed. The difference in hydrogen bonding formed with the -OH next to the chiral center of the analytes may help to increase chiral discrimination and gave rise to a bigger separation factor. In addition, the longer side chain in the hydrophobic phenyl ring of the enantiomer was not beneficial for enantioseparation and the chiral selectivity factor was found to correspond to the difference in binding free energy. PMID- 22312282 TI - Assessment of Aspergillus fumigatus in guinea pig bronchoalveolar lavages and pulmonary tissue by culture and realtime polymerase chain reaction studies. AB - In this study we pursued a diagnostic target in Aspergillus fumigatus (AF) by using qualitative Realtime PCR combined with proprietary DNA primers and a hydrolysis probe specific for this fungal target. Qualitative Realtime PCR is a diagnostic tool that utilizes Realtime PCR technology and detects the presence or absence target specific DNA within a predetermined detection range. Respiratory tissue and fluids from experimentally infected guinea pigs were tested by extracting DNA from the samples which were amplified and detected using AF specific DNA primers and probe. This study included qualitative evaluations of all specimens for the presence of the DNA of AF. The findings in the tissues after AF infection were compared to the numbers of spores in aerosolized samples used to inoculate the animals. Results demonstrated that the specific probe and primer set could detect the presence or absence of AF DNA in the sample. The qualitative detection limit of the assay ranged from 6 * 10(4) copies to 6 copies. Since blood cultures are rarely positive for Aspergillosis, our data indicate that qualitative Realtime PCR, in combination with the appropriate DNA primers and probe can serve as an effective diagnostic tool in the early detection of fungal infections. PMID- 22312283 TI - Nanostructured biomaterials for tissue engineered bone tissue reconstruction. AB - Bone tissue engineering strategies are emerging as attractive alternatives to autografts and allografts in bone tissue reconstruction, in particular thanks to their association with nanotechnologies. Nanostructured biomaterials, indeed, mimic the extracellular matrix (ECM) of the natural bone, creating an artificial microenvironment that promotes cell adhesion, proliferation and differentiation. At the same time, the possibility to easily isolate mesenchymal stem cells (MSCs) from different adult tissues together with their multi-lineage differentiation potential makes them an interesting tool in the field of bone tissue engineering. This review gives an overview of the most promising nanostructured biomaterials, used alone or in combination with MSCs, which could in future be employed as bone substitutes. Recent works indicate that composite scaffolds made of ceramics/metals or ceramics/polymers are undoubtedly more effective than the single counterparts in terms of osteoconductivity, osteogenicity and osteoinductivity. A better understanding of the interactions between MSCs and nanostructured biomaterials will surely contribute to the progress of bone tissue engineering. PMID- 22312284 TI - Mechanisms of action of (meth)acrylates in hemolytic activity, in vivo toxicity and dipalmitoylphosphatidylcholine (DPPC) liposomes determined using NMR spectroscopy. AB - We investigated the quantitative structure-activity relationships between hemolytic activity (log 1/H(50)) or in vivo mouse intraperitoneal (ip) LD(50) using reported data for alpha,beta-unsaturated carbonyl compounds such as (meth)acrylate monomers and their (13)C-NMR beta-carbon chemical shift (delta). The log 1/H(50) value for methacrylates was linearly correlated with the deltaC(beta) value. That for (meth)acrylates was linearly correlated with log P, an index of lipophilicity. The ipLD(50) for (meth)acrylates was linearly correlated with deltaC(beta) but not with log P. For (meth)acrylates, the deltaC(beta) value, which is dependent on the pi-electron density on the beta carbon, was linearly correlated with PM3-based theoretical parameters (chemical hardness, eta; electronegativity, chi; electrophilicity, omega), whereas log P was linearly correlated with heat of formation (HF). Also, the interaction between (meth)acrylates and DPPC liposomes in cell membrane molecular models was investigated using (1)H-NMR spectroscopy and differential scanning calorimetry (DSC). The log 1/H(50) value was related to the difference in chemical shift (DeltadeltaHa) (Ha: H (trans) attached to the beta-carbon) between the free monomer and the DPPC liposome-bound monomer. Monomer-induced DSC phase transition properties were related to HF for monomers. NMR chemical shifts may represent a valuable parameter for investigating the biological mechanisms of action of (meth)acrylates. PMID- 22312285 TI - Invasive fungal infections in patients with hematologic malignancies (aurora project): lights and shadows during 18-months surveillance. AB - The aim of this multicenter prospective study was to evaluate the incidence of invasive fungal infections (IFIs) in adult and pediatric patients with hematologic malignancies, involving nine nosocomial facilities in Southern Italy over a period of 18 months. Furthermore, results of an environmental microbial surveillance routinely carried out in some of the enrolled hospitals are reported. A total of 589 onco-hematological patients were enrolled and 27 IFIs were documented. The main infections were caused by yeasts, more than filamentous fungi (overall incidence of 2.7% and 1.9%, respectively). The yeasts were mainly represented by Candida spp. (87.5%), all isolated by blood cultures; C. parapsilosis was the most common species. Among mould infections, the most frequent site was the lung, with regard to aspergillosis (81.8%). In six of the 10 patients with suspected aspergillosis, the diagnosis was made by the detection of galactomannan and (1,3)-beta-d-glucan antigens. The microbiological surveillance carried out on 156 air, 312 water and 312 surface samples revealed low environmental contamination: Alternaria alternata was the only fungus isolated from two surface samples. Our data, especially the low occurrence of filamentous fungi, suggest a particular local epidemiology. Further studies are needed to confirm this microbiological trend in onco-hematological patients in Southern Italy, the results of which might be helpful to improve the management of these patients. PMID- 22312286 TI - Development of an innovative nutraceutical fermented beverage from herbal mate (Ilex paraguariensis A.St.-Hil.) extract. AB - Herbal mate (Ilex paraguariensis A.St.-Hil.) leaves are traditionally used for their stimulant, antioxidant, antimicrobial, and diuretic activity, presenting as principal components polyphenolic compounds. The aim of this work was to develop an innovative, non-dairy, functional, probiotic, fermented beverage using herbal mate extract as a natural ingredient which would also be hypocholesterolemic and hepatoprotective. Among different strains used, Lactobacillus acidophilus was selected as the best for fermentation. The addition of honey positively affected the development of L. acidophilus and the formulated beverage maintained microbial stability during shelf life. Key ingredients in the extract included xanthines, polyphenols and other antioxidants with potential health benefits for the consumer. Caffeine levels and antioxidant activity were also studied. Acceptable levels of caffeine and large antioxidant capacity were observed for the formulation when compared to other antioxidant beverages. An advantage of this product is the compliance to organic claims, while providing caffeine, other phyto-stimulants and antioxidant compounds without the addition of synthetic components or preservatives in the formulation. Sensorial analysis demonstrated that the beverage had good consumer acceptance in comparison to two other similar commercial beverages. Therefore, this beverage could be used as a new, non-dairy vehicle for probiotic consumption, especially by vegetarians and lactose intolerant consumers. It is expected that such a product will have good market potential in an era of functional foods. PMID- 22312287 TI - Procyanidins from wild grape (Vitis amurensis) seeds regulate ARE-mediated enzyme expression via Nrf2 coupled with p38 and PI3K/Akt pathway in HepG2 cells. AB - Procyanidins, polymers of flavan-3-ol units, have been reported to exhibit many beneficial health effects such as antioxidant and anti-carcinogenic effects. In this study, we investigated the cancer chemopreventive properties of procyanidins from wild grape (Vitis amurensis) seeds in particular their roles in inducing phase II detoxifying/antioxidant enzymes as well as in modulating the upstream kinases. Ethanolic extract of V. amurensis seeds was fractionated with a series of organic solvents and finally separated into six fractions, F1-F6. Chemical properties of the procyanidins were analyzed by vanillin assay, BuOH-HCl test, and depolymerization with phloroglucinol followed by LC/MS analysis. The F5 had the highest procyanidin content among all the fractions and strongly induced the reporter activity of antioxidant response element as well as the protein expression of nuclear factor E2-related factor (Nrf2) in HepG2 human hepatocarcinoma cells. The procyanidin-rich F5 also strongly induced the expression of the phase II detoxifying and antioxidant enzymes such as NAD(P)H:quinone oxidoreductase1 and hemeoxygenase1. Phosphorylations of the upstream kinases such as MAPKs and PI3K/Akt were significantly increased by treatment with procyanidin fraction. In addition, the procyanidin-mediated Nrf2 expression was partly attenuated by PI3K inhibitor LY294002, and almost completely by p38 inhibitor SB202190, but neither by JNK inhibitor SP600125 nor by MEK1/2 inhibitor U0126. Taken together, the procyanidins from wild grape seeds could be used as a potential natural chemopreventive agent through Nrf2/ARE mediated phase II detoxifying/antioxidant enzymes induction via p38 and PI3K/Akt pathway. PMID- 22312288 TI - Evaluation of a centrifuged double Y-shape microfluidic platform for simple continuous cell environment exchange. AB - We have demonstrated the efficacy of a microfluidic medium exchange method for single cells using passive centrifugal force of a rotating microfluidic-chip based platform. At the boundary of two laminar flows at the gathering area of two microfluidic pathways in a Y-shape, the cells were successfully transported from one laminar flow to the other, without mixing the two microfluidic mediums of the two laminar flows during cell transportation, within 5 s with 1 g (150 rpm) to 36.3 g (900 rpm) acceleration, with 93.5% efficiency. The results indicate that this is one of the most simple and precise tools for exchanging medium in the shortest amount of time. PMID- 22312289 TI - Lewis y regulate cell cycle related factors in ovarian carcinoma cell RMG-I in vitro via ERK and Akt signaling pathways. AB - OBJECTIVE: To investigate the effect of Lewis y overexpression on the expression of proliferation-related factors in ovarian cancer cells. METHODS: mRNA levels of cyclins, CDKs, and CKIs were measured in cells before and after transfection with the alpha1,2-fucosyltransferase gene by real-time PCR, and protein levels of cyclins, CDKs and CKIs were determined in cells before and after gene transfection by Western blot. RESULTS: Lewis y overexpression led to an increase in both mRNA and protein expression levels of cyclin A, cyclin D1 and cyclin E in ovarian cancer cells, decrease in both mRNA and protein expression levels of p16 and p21, and decrease of p27 at only the protein expression level without change in its mRNA level. There were no differences in proteins and the mRNA levels of CDK2, CDK4 and CDK6 before and after gene transfection. Anti-Lewis y antibody, ERK and PI3K pathway inhibitors PD98059 and LY294002 reduced the difference in cyclin and CKI expression caused by Lewis y overexpression. CONCLUSION: Lewis y regulates the expression of cell cycle-related factors through ERK/MAPK and PI3K/Akt signaling pathways to promote cell proliferation. PMID- 22312290 TI - MiRNAs and LincRNAs: Could they be considered as biomarkers in colorectal cancer? AB - Recent advances in the field of RNA research have provided compelling evidence implicating microRNA (miRNA) and long non-coding RNA molecules in many diverse and substantial biological processes, including transcriptional and post transcriptional regulation of gene expression, genomic imprinting, and modulation of protein activity. Thus, studies of non-coding RNA (ncRNA) may contribute to the discovery of possible biomarkers in human cancers. Considering that the response to chemotherapy can differ amongst individuals, researchers have begun to isolate and identify the genes responsible. Identification of targets of this ncRNA associated with cancer can suggest that networks of these linked to oncogenes or tumor suppressors play pivotal roles in cancer development. Moreover, these ncRNA are attractive drug targets since they may be differentially expressed in malignant versus normal cells and regulate expression of critical proteins in the cell. This review focuses on ncRNAs that are differently expressed in malignant tissue, and discusses some of challenges derived from their use as potential biomarkers of tumor properties. PMID- 22312291 TI - Icariin ameliorates streptozotocin-induced diabetic retinopathy in vitro and in vivo. AB - This study investigated the effect of Icariin (ICA) supplementation on diabetic retinopathy (DR) in a streptozotocin-induced diabetic rat model system. Fifty Sprague Dawley rats were randomly distributed into a control group and a streptozotocin-induced diabetes group. Diabetic rats were randomly divided into two groups; one group received ICA 5 mg/kg/day for 12 weeks by oral gavage; the other group received saline gavage as a placebo. Retinal morphological changes, endothelial markers (RECA), collagen IV (Col-IV), vascular endothelial growth factor (VEGF), and neuropathic changes (Thy-1 and Brn3a expression) of the retinal ganglion cells (RGCs) were investigated. The effects of ICA at various concentrations (0, 10(1), 10(2), 10(3) nmol/mL) on neurite growth were investigated also in retinal ganglion cells (RGC) cultured from both diabetic and normal animals. Numerous pathological changes (deceased expression of RECA, VEGF, Thy-1, and Brn3a as well as decreased Collagen IV and Muller cell content) were noted in the retinal vessels of diabetic rats; these changes were attenuated in diabetic animals that received ICA. ICA enhanced neurite growth in RGC from both normal rats and diabetic rats in a dose dependent fashion. ICA may be useful in the treatment of diabetic retinopathy. Further investigations are indicated. PMID- 22312292 TI - Molecular cloning, characterization and predicted structure of a putative copper zinc SOD from the camel, Camelus dromedarius. AB - Superoxide dismutase (SOD) is the first line of defense against oxidative stress induced by endogenous and/or exogenous factors and thus helps in maintaining the cellular integrity. Its activity is related to many diseases; so, it is of importance to study the structure and expression of SOD gene in an animal naturally exposed most of its life to the direct sunlight as a cause of oxidative stress. Arabian camel (one humped camel, Camelus dromedarius) is adapted to the widely varying desert climatic conditions that extremely changes during daily life in the Arabian Gulf. Studying the cSOD1 in C. dromedarius could help understand the impact of exposure to direct sunlight and desert life on the health status of such mammal. The full coding region of a putative CuZnSOD gene of C. dromedarius (cSOD1) was amplified by reverse transcription PCR and cloned for the first time (gene bank accession number for nucleotides and amino acids are JF758876 and AEF32527, respectively). The cDNA sequencing revealed an open reading frame of 459 nucleotides encoding a protein of 153 amino acids which is equal to the coding region of SOD1 gene and protein from many organisms. The calculated molecular weight and isoelectric point of cSOD1 was 15.7 kDa and 6.2, respectively. The level of expression of cSOD1 in different camel tissues (liver, kidney, spleen, lung and testis) was examined using Real Time-PCR. The highest level of cSOD1 transcript was found in the camel liver (represented as 100%) followed by testis (45%), kidney (13%), lung (11%) and spleen (10%), using 18S ribosomal subunit as endogenous control. The deduced amino acid sequence exhibited high similarity with Cebus apella (90%), Sus scrofa (88%), Cavia porcellus (88%), Mus musculus (88%), Macaca mulatta (87%), Pan troglodytes (87%), Homo sapiens (87%), Canis familiaris (86%), Bos taurus (86%), Pongo abelii (85%) and Equus caballus (82%). Phylogenetic analysis revealed that cSOD1 is grouped together with S. scrofa. The predicted 3D structure of cSOD1 showed high similarity with the human and bovine CuZnSOD homologues. The Root-mean-square deviation (rmsd) between cSOD1/hSOD1 and cSOD1/bSOD1 superimposed structure pairs were 0.557 and 0.425 A. The Q-score of cSOD1-hSOD1 and cSOD1-bSOD1 were 0.948 and 0.961, respectively. PMID- 22312293 TI - Structural modeling and biochemical characterization of recombinant KPN_02809, a zinc-dependent metalloprotease from Klebsiella pneumoniae MGH 78578. AB - Klebsiella pneumoniae is a Gram-negative, cylindrical rod shaped opportunistic pathogen that is found in the environment as well as existing as a normal flora in mammalian mucosal surfaces such as the mouth, skin, and intestines. Clinically it is the most important member of the family of Enterobacteriaceae that causes neonatal sepsis and nosocomial infections. In this work, a combination of protein sequence analysis, structural modeling and molecular docking simulation approaches were employed to provide an understanding of the possible functions and characteristics of a hypothetical protein (KPN_02809) from K. pneumoniae MGH 78578. The computational analyses showed that this protein was a metalloprotease with zinc binding motif, HEXXH. To verify this result, a ypfJ gene which encodes for this hypothetical protein was cloned from K. pneumoniae MGH 78578 and the protein was overexpressed in Escherichia coli BL21 (DE3). The purified protein was about 32 kDa and showed maximum protease activity at 30 degrees C and pH 8.0. The enzyme activity was inhibited by metalloprotease inhibitors such as EDTA, 1,10-phenanthroline and reducing agent, 1,4-dithiothreitol (DTT). Each molecule of KPN_02809 protein was also shown to bind one zinc ion. Hence, for the first time, we experimentally confirmed that KPN_02809 is an active enzyme with zinc metalloprotease activity. PMID- 22312294 TI - Characterization of electrosynthesized conjugated polymer-carbon nanotube composite: optical nonlinearity and electrical property. AB - The effects of multi-walled carbon nanotube (MWNT) concentration on the structural, optical and electrical properties of conjugated polymer-carbon nanotube composite are discussed. Multi-walled carbon nanotube-polypyrrole nanocomposites were synthesized by electrochemical polymerization of monomers in the presence of different amounts of MWNTs using sodium dodecylbenzensulfonate (SDBS) as surfactant at room temperature and normal pressure. Field emission scanning electron microscopy (FESEM) indicates that the polymer is wrapped around the nanotubes. Measurement of the nonlinear refractive indices (n(2)) and the nonlinear absorption (beta) of the samples with different MWNT concentrations measurements were performed by a single Z-scan method using continuous wave (CW) laser beam excitation wavelength of lambda = 532 nm. The results show that both nonlinear optical parameters increased with increasing the concentration of MWNTs. The third order nonlinear susceptibilities were also calculated and found to follow the same trend as n(2) and beta. In addition, the conductivity of the composite film was found to increase rapidly with the increase in the MWNT concentration. PMID- 22312295 TI - Effect of enzymatic treatment of different starch sources on the in vitro rate and extent of starch digestion. AB - Gelatinized wheat, potato and waxy maize starches were treated enzymatically in order to increase the degree of branching of the amylopectin fraction and thereby change the starch degradation profile towards a higher proportion of slowly digestible starch (SDS). The materials were characterized by single-pulse (1)H HR MAS NMR spectroscopy and in vitro digestion profile according to the Englyst procedure. Using various concentrations and incubation times with branching enzyme (EC 2.4.1.18) without or with additional treatment with the hydrolytic enzymes; beta-amylase (EC 3.2.1.2), alpha-glucosidase (EC 3.2.1.20), or amyloglucosidase (EC 3.2.1.3) the proportion of alpha-(1-6) linkages was increased by up to a factor of 4.1, 5 and 5.8 in waxy maize, wheat and potato starches, respectively. The proportion of SDS was significantly increased when using hydrolytic enzymes after treatment with branching enzyme but it was only for waxy maize that the proportion of alpha-(1-6) bonds and the in vitro digestion profile was significantly correlated. PMID- 22312296 TI - Improvement of thermal stability via outer-loop ion pair interaction of mutated T1 lipase from Geobacillus zalihae strain T1. AB - Mutant D311E and K344R were constructed using site-directed mutagenesis to introduce an additional ion pair at the inter-loop and the intra-loop, respectively, to determine the effect of ion pairs on the stability of T1 lipase isolated from Geobacillus zalihae. A series of purification steps was applied, and the pure lipases of T1, D311E and K344R were obtained. The wild-type and mutant lipases were analyzed using circular dichroism. The T(m) for T1 lipase, D311E lipase and K344R lipase were approximately 68.52 degrees C, 70.59 degrees C and 68.54 degrees C, respectively. Mutation at D311 increases the stability of T1 lipase and exhibited higher T(m) as compared to the wild-type and K344R. Based on the above, D311E lipase was chosen for further study. D311E lipase was successfully crystallized using the sitting drop vapor diffusion method. The crystal was diffracted at 2.1 A using an in-house X-ray beam and belonged to the monoclinic space group C2 with the unit cell parameters a = 117.32 A, b = 81.16 A and c = 100.14 A. Structural analysis showed the existence of an additional ion pair around E311 in the structure of D311E. The additional ion pair in D311E may regulate the stability of this mutant lipase at high temperatures as predicted in silico and spectroscopically. PMID- 22312297 TI - Freshwater plants synthesize sulfated polysaccharides: heterogalactans from Water Hyacinth (Eicchornia crassipes). AB - Sulfated polysaccharides (SP) are found mainly in seaweeds and animals. To date, they have only been found in six plants and all inhabit saline environments. Furthermore, there are no reports of SP in freshwater or terrestrial plants. As such, this study investigated the presence of SP in freshwaters Eichhornia crassipes, Egeria densa, Egeria naja, Cabomba caroliniana, Hydrocotyle bonariensis and Nymphaea ampla. Chemical analysis identified sulfate in N. ampla, H. bonariensis and, more specifically, E. crassipes. In addition, chemical analysis, FT-IR spectroscopy, histological analysis, scanning electron microscopy (SEM) and energy-dispersive X-ray analysis (EDXA), as well as agarose gel electrophoresis detected SP in all parts of E. crassipes, primarily in the root (epidermis and vascular bundle). Galactose, glucose and arabinose are the main monosaccharides found in the sulfated polysaccharides from E. crassipes. In activated partial thromboplastin time (APTT) test, to evaluate the intrinsic coagulation pathway, SP from the root and rhizome prolonged the coagulation time to double the baseline value, with 0.1 mg/mL and 0.15 mg/mL, respectively. However, SP from the leaf and petiole showed no anticoagulant activity. Eichornia SP demonstrated promising anticoagulant potential and have been selected for further studies on bioguided fractionation; isolation and characterization of pure polysaccharides from this species. Additionally in vivo experiments are needed and are already underway. PMID- 22312298 TI - Isoflurane protects against human endothelial cell apoptosis by inducing sphingosine kinase-1 via ERK MAPK. AB - Endothelial dysfunction is a major clinical problem affecting virtually every patient requiring critical care. Volatile anesthetics are frequently used during the perioperative period and protect the heart and kidney against ischemia and reperfusion injury. We aimed to determine whether isoflurane, the most commonly used volatile anesthetic in the USA, protects against endothelial apoptosis and necrosis and the mechanisms involved in this protection. Human endothelial EA.hy926 cells were pretreated with isoflurane or carrier gas (95% room air + 5% CO(2)) then subjected to apoptosis with tumor necrosis factor-alpha or to necrosis with hydrogen peroxide. DNA laddering and in situ Terminal Deoxynucleotidyl Transferase Biotin-dUTP Nick-End Labeling (TUNEL) staining determined EA.hy926 cell apoptosis and percent LDH released determined necrosis. We also determined whether isoflurane modulates the expression and activity of sphingosine kinase-1 (SK1) and induces the phosphorylation of extracellular signal regulated kinase (ERK MAPK) as both enzymes are known to protect against cell death. Isoflurane pretreatment significantly decreased apoptosis in EA.hy926 cells as evidenced by reduced TUNEL staining and DNA laddering without affecting necrosis. Mechanistically, isoflurane induces the phosphorylation of ERK MAPK and increased SK1 expression and activity in EA.hy926 cells. Finally, selective blockade of SK1 (with SKI-II) or S1P(1) receptor (with W146) abolished the anti apoptotic effects of isoflurane. Taken together, we demonstrate that isoflurane, in addition to its potent analgesic and anesthetic properties, protects against endothelial apoptosis most likely via SK1 and ERK MAPK activation. Our findings have significant clinical implication for protection of endothelial cells during the perioperative period and patients requiring critical care. PMID- 22312299 TI - Boesenbergia pandurata attenuates diet-induced obesity by activating AMP activated protein kinase and regulating lipid metabolism. AB - Obesity, a chronic metabolic disorder, is characterized by enlarged fat mass and dysregulation of lipid metabolism. The medicinal plant, Boesenbergia pandurata (Roxb.) Schltr., has been reported to possess anti-oxidative and anti inflammatory properties; however, its anti-obesity activity is unexplored. The present study was conducted to determine whether B. pandurata extract (BPE), prepared from its rhizome parts, attenuated high-fat diet (HFD)-induced obesity in C57BL/6J mice. The molecular mechanism was investigated in 3T3-L1 adipocytes and HepG2 human hepatoma cells. BPE treatment decreased triglyceride accumulation in both 3T3-L1 adipocytes and HepG2 hepatocytes by activating AMP-activated protein kinase (AMPK) signaling and regulating the expression of lipid metabolism related proteins. In the animal model, oral administration of BPE (200 mg/kg/day for 8 weeks) significantly reduced HFD-induced body weight gain without altering the amount of food intake. In addition, elevated serum levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides were suppressed by BPE administration. Fat pad masses were reduced in BPE-treated mice, as evidenced by reduced adipocyte size. Furthermore, BPE protected against the development of nonalcoholic fatty liver by decreasing hepatic triglyceride accumulation. BPE also activated AMPK signaling and altered the expression of lipid metabolism-related proteins in white adipose tissue and liver. Taken together, these findings indicate that BPE attenuates HFD-induced obesity by activating AMPK and regulating lipid metabolism, suggesting a potent anti-obesity agent. PMID- 22312300 TI - Photostability of Iiovaline and its precursor 5-Ethyl-5- methylhydantoin exposed to simulated space radiations. AB - Aqueous solutions of isovaline and its precursor molecule, 5-ethyl-5 methylhydantoin, were irradiated with ultraviolet and gamma-ray photons, to evaluate their structural stability against space radiation. The degree of photolysis was measured and irradiation products were identified using chiral, reversed-phase and ion-exchange high-performance liquid chromatography. The experimental results show that the degree of photolysis of 5-ethyl-5 methylhydantoin is more significant than that of isovaline under ultraviolet light irradiation, while the results under gamma-ray irradiation are the opposite. As the products of isovaline photolysis, aspartic acid, serine, glutamic acid and alanine were dominantly detected. PMID- 22312301 TI - Plasmonic molecular nanohybrids-spectral dependence of fluorescence quenching. AB - We demonstrate strong spectral dependence of the efficiency of fluorescence quenching in molecular systems composed of organic dyes and gold nanoparticles. In order to probe the coupling with metallic nanoparticles we use dyes with varied spectral overlap between the plasmon resonance and their absorption. Hybrid molecular structures were obtained via conjugation of metallic nanoparticles with the dyes using biotin-streptavidin linkage. For dyes featuring absorption above the plasmon excitation in gold nanoparticles, laser excitation induces minute changes in the fluorescence intensity and its lifetime for both conjugated and non-conjugated mixtures, which are the reference. In contrast, when the absorption of the dye overlaps with the plasmon resonance, the effect is quite dramatic, reaching 85% and 95% fluorescence quenching for non-conjugated and conjugated mixtures, respectively. The degree of fluorescence quenching strongly depends upon the concentration of metallic nanoparticles. Importantly, the origin of the fluorescence quenching is different in the case of the conjugated mixture, as evidenced by time-resolved fluorescence. For conjugated mixtures of dyes resonant with plasmon, excitation features two-exponential decay. This is in contrast to the single exponential decay measured for the off resonant configuration. The results provide valuable insight into spectral dependence of the fluorescence quenching in molecular assemblies involving organic dyes and metallic nanoparticles. PMID- 22312302 TI - Structural elucidation and bioactivity of biflavonoids from the stems of Wikstroemia taiwanensis. AB - Three new biflavonoids, wikstaiwanones A-C (1-3), along with four known compounds (4-7) were isolated from the stems of Wikstroemia taiwanensis (Thymelaeaceae). Their structures were elucidated by spectroscopic analysis. Compounds 4 and 5 showed antitubercular activity against Mycobacterium tuberculosis with MIC values of 15 MUg/mL, respectively. PMID- 22312303 TI - Cloning and expression analysis of a PISTILLATA homologous gene from pineapple (Ananas comosus L. Merr). AB - PISTILLATA (PI)-like genes are crucial regulators of flowering in angiosperms. A homologue of PI, designated as AcPI (Genbank accession number HQ717796), was isolated from pineapple cultivar Comte de Paris by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE). The cDNA sequence of AcPI is 907 bp in length and contains an open reading frame of 594 bp, which encodes a protein of 197 amino acids. The molecular weight was 2.29 kDa and the isoelectric point was 9.28. The alignment showed that AcPI had a high identity with CsPIC2 (78.6%), AoPI (77.4%), OrcPI (75.7%) and HPI2 (72.4%). Quantitative real-time polymerase chain reaction (qRT-PCR) analyses in different tissues showed that the expression pattern of AcPI was different from the B-class genes in eudicots. AcPI was expressed in all the tissues investigated. The expression level was very low in fruit stems, bracts, leaves and sepals, high in petals and carpels, and moderate in apical meristems, flesh and stamens. The qRT PCR analyses in different stages indicated that the expression of AcPI reached the highest level at 40 days after flower inducement, when the multiple fruit and floral organs were forming. It proved the important role of AcPI in floral organs and fruit development. The 35S::AcPI transgenic Arabidopsis plants flowered earlier and had more inflorescences or branches than wild type plants. PMID- 22312304 TI - Studies on bioflocculant production by Arthrobacter sp. Raats, a freshwater bacteria isolated from Tyume River, South Africa. AB - A bioflocculant-producing bacteria was isolated from Tyume River in the Eastern Cape Province, South Africa and identified by 16S rRNA gene nucleotide sequence to have 91% similarity to Arthrobacter sp. 5J12A, and the nucleotide sequence was deposited in GenBank as Arthrobacter sp. Raats (accession number HQ875723). The bacteria produced an extracellular bioflocculant when grown aerobically in a production medium containing glucose as sole carbon source and had an initial pH of 7.0. Influences of carbon, nitrogen and metal ions sources, as well as initial pH on flocculating activity were investigated. The bacteria optimally produced the bioflocullant when lactose and urea were used as sole sources of carbon and nitrogen respectively with flocculating activities of 75.4% and 83.4% respectively. Also, the bacteria produced the bioflocculant optimally when initial pH of the medium was 7.0 (flocculating activity 84%), and when Mg(2+) was used as cation (flocculating activity 77%). Composition analyses indicated the bioflocculant to be principally a glycoprotein made up of about 56% protein and 25% total carbohydrate. PMID- 22312305 TI - On the several molecules and nanostructures of water. AB - This paper investigates the water molecule from a variety of viewpoints. Water can involve different isotopes of Hydrogen and Oxygen, it can form differently shaped isomer molecules, and, when frozen, it occupies space differently than most other substances do. The tool for conducting the investigation of all this is called 'Algebraic Chemistry'. This tool is a quantitative model for predicting the energy budget for all sorts of changes between different ionization states of atoms that are involved in chemical reactions and in changes of physical state. The model is based on consistent patterns seen in empirical data about ionization potentials, together with rational scaling laws that can interpolate and extrapolate for situations where no data are available. The results of the investigation of the water molecule include comments, both positive and negative, about technologies involving heavy water, poly water, Brown's gas, and cold fusion. PMID- 22312306 TI - Local mechanical stimulation of Mardin-Darby canine kidney cell sheets on temperature-responsive hydrogel. AB - Collective motion of cell sheets plays a role not only in development and repair, but also in devastating diseases such as cancer. However, unlike single-cell motility, collective motion of cell sheets involves complex cell-cell communication during migration; therefore, its mechanism is largely unknown. To elucidate propagation of signaling transduced by cell-cell interaction, we designed a hydrogel substrate that can cause local mechanical stretching of cell sheets. Poly (N-isopropyl acrylamide) (PNIPAAm) hydrogel is a temperature responsive polymer gel whose volume changes isotropically in response to temperature changes below 37 degrees C. We designed a combined hydrogel substrate consisting of collagen-immobilized PNIPAAm as the local stimulation side and polyacrylamide (PAAm) as the non-stimulation side to assess propagation of mechanical transduction. Mardin-Darby canine kidney (MDCK) cells adhered to the collagen-immobilized PNIPAAm gel increased it area and were flattened as the gel swelled with temperature decrease. E-cadherin in these cells became undetectable in some domains, and actin stress fibers were more clearly observed at the cell base. In contrast, E-cadherin in cells adhered to the collagen immobilized PAAm side was equally stained as that in cells adhered to the collagen-immobilized PAAm side even after temperature decrease. ERK1/2 MAPK activation of cells on the non-stimulated substrate occurred after partial stretching of the cell sheet suggesting the propagation of signaling. These results indicate that a change in the balance of mechanical tension induced by partial stretching of cell sheets leads to activation and propagation of the cell signaling. PMID- 22312307 TI - The effect of temozolomide/poly(lactide-co-glycolide) (PLGA)/nano-hydroxyapatite microspheres on glioma U87 cells behavior. AB - In this study, we investigated the effects of temozolomide (TMZ)/Poly (lactide-co glycolide)(PLGA)/nano-hydroxyapatite microspheres on the behavior of U87 glioma cells. The microspheres were fabricated by the "Solid/Water/Oil" method, and they were characterized by using X-Ray diffraction, scanning electron microscopy and differential scanning calorimetry. The proliferation, apoptosis and invasion of glioma cells were evaluated by MTT, flow cytometry assay and Transwell assay. The presence of the key invasive gene, alpha(V)beta3 integrin, was detected by the RT PCR and Western blot method. It was found that the temozolomide/PLGA/nano hydroxyapatite microspheres have a significantly diminished initial burst of drug release, compared to the TMZ laden PLGA microspheres. Our results suggest they can significantly inhibit the proliferation and invasion of glioma cells, and induce their apoptosis. Additionally, alpha(V)beta3 integrin was also reduced by the microspheres. These data suggest that by inhibiting the biological behavior of glioma cells in vitro, the newly designed temozolomide/PLGA/nano hydroxyapatite microspheres, as controlled drug release carriers, have promising potential in treating glioma. PMID- 22312309 TI - Isolation and characterization of new 24 microsatellite DNA markers for golden cuttlefish (Sepia esculenta). AB - Twenty-four microsatellite DNA markers were isolated and characterized for golden cuttlefish (Sepia esculenta) from a (GT)(13)-enriched genomic library. Loci were tested in 48 individuals from Jiaozhou bay of China. The numbers of alleles per locus ranged from two to 25 with an average of 10.3. The observed and expected heterozygosities ranged from 0.063 to 0.896 and from 0.137 to 0.953, with averages of 0.519 and 0.633, respectively. Six loci significantly deviated from Hardy-Weinberg equilibrium after Bonferroni's correction and no significant linkage disequilibrium between loci pairs was detected. These microsatellite markers would be useful for analyzing the population genetic structure to make conservation and management decisions for S. esculenta. PMID- 22312308 TI - Clinical significance of serum biomarkers in pediatric solid mediastinal and abdominal tumors. AB - Childhood cancer is the leading cause of death by disease among U.S. children between infancy and age 15. Despite successes in treating solid tumors such as Wilms tumor, disappointments in the outcomes of high-risk solid tumors like neuroblastoma have precipitated efforts towards the early and accurate detection of these malignancies. This review summarizes available solid tumor serum biomarkers with a special focus on mediastinal and abdominal cancers in children. PMID- 22312310 TI - High-Dimensional descriptor selection and computational QSAR modeling for antitumor activity of ARC-111 analogues Based on Support Vector Regression (SVR). AB - To design ARC-111 analogues with improved efficiency, we constructed the QSAR of 22 ARC-111 analogues with RPMI8402 tumor cells. First, the optimized support vector regression (SVR) model based on the literature descriptors and the worst descriptor elimination multi-roundly (WDEM) method had similar generalization as the artificial neural network (ANN) model for the test set. Secondly, seven and 11 more effective descriptors out of 2,923 features were selected by the high dimensional descriptor selection nonlinearly (HDSN) and WDEM method, and the SVR models (SVR3 and SVR4) with these selected descriptors resulted in better evaluation measures and a more precise predictive power for the test set. The interpretability system of better SVR models was further established. Our analysis offers some useful parameters for designing ARC-111 analogues with enhanced antitumor activity. PMID- 22312311 TI - microRNA response to Listeria monocytogenes infection in epithelial cells. AB - microRNAs represent a family of very small non-coding RNAs that control several physiologic and pathologic processes, including host immune response and cancer by antagonizing a number of target mRNAs. There is limited knowledge about cell expression and the regulatory role of microRNAs following bacterial infections. We investigated whether infection with a Gram-positive bacterium leads to altered expression of microRNAs involved in the host cell response in epithelial cells. Caco-2 cells were infected with Listeria monocytogenes EGD-e, a mutant strain (DeltainlAB or Deltahly) or incubated with purified listeriolysin (LLO). Total RNA was isolated and microRNA and target gene expression was compared to the expression in non-infected cells using microRNA microarrays and qRT-PCR. We identified and validated five microRNAs (miR- 146b, miR-16, let-7a1, miR-145 and miR-155) that were significantly deregulated following listerial infection. We show that expression patterns of particular microRNAs strongly depend on pathogen localization and the presence of bacterial effector proteins. Strikingly, miR-155 which was shown to have an important role in inflammatory responses during infection was induced by wild-type bacteria, by LLO-deficient bacteria and following incubation with purified LLO. It was downregulated following DeltainlAB infection indicating a new potent role for internalins in listerial pathogenicity and miRNA regulation. Concurrently, we observed differences in target transcript expression of the investigated miRNAs. We provide first evidence that L. monocytogenes infection leads to deregulation of a set of microRNAs with important roles in host response. Distinct microRNA expression depends on both LLO and pathogen localization. PMID- 22312312 TI - Inhibition of AKT2 enhances sensitivity to gemcitabine via regulating PUMA and NF kappaB signaling pathway in human pancreatic ductal adenocarcinoma. AB - Invasion, metastasis and resistance to conventional chemotherapeutic agents are obstacles to successful treatment of pancreatic cancer, and a better understanding of the molecular basis of this malignancy may lead to improved therapeutics. In the present study, we investigated whether AKT2 silencing sensitized pancreatic cancer L3.6pl, BxPC-3, PANC-1 and MIAPaCa-2 cells to gemcitabine via regulating PUMA (p53-upregulated modulator of apoptosis) and nuclear factor (NF)-kappaB signaling pathway. MTT, TUNEL, EMSA and NF-kappaB reporter assays were used to detect tumor cell proliferation, apoptosis and NF kappaB activity. Western blotting was used to detect different protein levels. Xenograft of established tumors was used to evaluate primary tumor growth and apoptosis after treatment with gemcitabine alone or in combination with AKT2 siRNA. Gemcitabine activated AKT2 and NF-kappaB in MIAPaCa-2 and L3.6pl cells in vitro or in vivo, and in PANC-1 cells only in vivo. Gemcitabine only activated NF kappaB in BxPC-3 cells in vitro. The presence of PUMA was necessary for gemcitabine-induced apoptosis only in BxPC-3 cells in vitro. AKT2 inhibition sensitized gemcitabine-induced apoptosis via PUMA upregulation in MIAPaCa-2 cells in vitro, and via NF-kappaB activity inhibition in L3.6pl cells in vitro. In PANC 1 and MIAPaCa-2 cells in vivo, AKT2 inhibition sensitized gemcitabine-induced apoptosis and growth inhibition via both PUMA upregulation and NF-kappaB inhibition. We suggest that AKT2 inhibition abrogates gemcitabine-induced activation of AKT2 and NF-kappaB, and promotes gemcitabine-induced PUMA upregulation, resulting in chemosensitization of pancreatic tumors to gemcitabine, which is probably an important strategy for the treatment of pancreatic cancer. PMID- 22312313 TI - Targeting protective autophagy exacerbates UV-triggered apoptotic cell death. AB - Autophagy is activated by various stresses, including DNA damage, and previous studies of DNA damage-induced autophagy have focused on the response to chemotherapeutic drugs, ionizing radiation, and reactive oxygen species. In this study, we investigated the biological significance of autophagic response to ultraviolet (UV) irradiation in A549 and H1299 cells. Our results indicated that UV induces on-rate autophagic flux in these cells. Autophagy inhibition resulting from the knockdown of beclin-1 and Atg5 reduced cell viability and enhanced apoptosis. Moreover, we found that ATR phosphorylation was accompanied by microtubule-associated protein 1 light chain 3B II (LC3B-II) expression during the early phases following UV irradiation, which is a well-established inducer of ATR. Knocking down ATR further attenuated the reduction in LC3B-II at early stages in response to UV treatment. Despite the potential role of ATR in autophagic response, reduced ATR expression does not affect autophagy induction during late phases (24 and 48 h after UV treatment). The result is consistent with the reduced ATR phosphorylation at the same time points and suggests that autophagic response at this stage is activated via a distinct pathway. In conclusion, this study demonstrated that autophagy acts as a cytoprotective mechanism against UV-induced apoptosis and that autophagy induction accompanied with apoptosis at late stages is independent of ATR activation. PMID- 22312314 TI - Disruption of axonal transport in motor neuron diseases. AB - Motor neurons typically have very long axons, and fine-tuning axonal transport is crucial for their survival. The obstruction of axonal transport is gaining attention as a cause of neuronal dysfunction in a variety of neurodegenerative motor neuron diseases. Depletions in dynein and dynactin-1, motor molecules regulating axonal trafficking, disrupt axonal transport in flies, and mutations in their genes cause motor neuron degeneration in humans and rodents. Axonal transport defects are among the early molecular events leading to neurodegeneration in mouse models of amyotrophic lateral sclerosis (ALS). Gene expression profiles indicate that dynactin-1 mRNA is downregulated in degenerating spinal motor neurons of autopsied patients with sporadic ALS. Dynactin-1 mRNA is also reduced in the affected neurons of a mouse model of spinal and bulbar muscular atrophy, a motor neuron disease caused by triplet CAG repeat expansion in the gene encoding the androgen receptor. Pathogenic androgen receptor proteins also inhibit kinesin-1 microtubule-binding activity and disrupt anterograde axonal transport by activating c-Jun N-terminal kinase. Disruption of axonal transport also underlies the pathogenesis of spinal muscular atrophy and hereditary spastic paraplegias. These observations suggest that the impairment of axonal transport is a key event in the pathological processes of motor neuron degeneration and an important target of therapy development for motor neuron diseases. PMID- 22312315 TI - The effect of secretory factors of adipose-derived stem cells on human keratinocytes. AB - The beneficial effects of adipose-derived stem cell conditioned medium (ADSC-CM) on skin regeneration have been reported. Although the mechanism of how ADSC-CM promotes skin regeneration is unclear, ADSC-CM contained various growth factors and it is an excellent raw material for skin treatment. ADSC-CM produced in a hypoxia condition of ADSC-in other words, Advanced Adipose-Derived Stem cell Protein Extract (AAPE)-has great merits for skin regeneration. In this study, human primary keratinocytes (HKs), which play fundamental roles in skin tissue, was used to examine how AAPE affects HK. HK proliferation was significantly higher in the experimental group (1.22 MUg/mL) than in the control group. DNA gene chip demonstrated that AAPE in keratinocytes (p < 0.05) notably affected expression of 290 identified transcripts, which were associated with cell proliferation, cycle and migration. More keratinocyte wound healing and migration was shown in the experimental group (1.22 MUg/mL). AAPE treatment significantly stimulated stress fiber formation, which was linked to the RhoA-ROCK pathway. We identified 48 protein spots in 2-D gel analysis and selected proteins were divided into 64% collagen components and 30% non-collagen components as shown by the MALDI-TOF analysis. Antibody array results contained growth factor/cytokine such as HGF, FGF-1, G-CSF, GM-CSF, IL-6, VEGF, and TGF-beta3 differing from that shown by 2-D analysis. CONCLUSION: AAPE activates HK proliferation and migration. These results highlight the potential of the topical application of AAPE in the treatment of skin regeneration. PMID- 22312316 TI - Prunella vulgaris suppresses HG-induced vascular inflammation via Nrf2/HO-1/eNOS activation. AB - Vascular inflammation is an important factor which can promote diabetic complications. In this study, the inhibitory effects of aqueous extract from Prunella vulgaris (APV) on high glucose (HG)-induced expression of cell adhesion molecules in human umbilical vein endothelial cells (HUVEC) are reported. APV decreased HG-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. APV also dose dependently inhibited HG-induced adhesion of HL-60 monocytic cells. APV suppressed p65 NF-kappaB activation in HG-treated cells. APV significantly inhibited the formation of intracellular reactive oxygen species (ROS). HG stimulated HUVEC secreted gelatinases, however, APV inhibited it. APV induced Akt phosphorylation as well as activation of heme oxygenase-1 (HO-1), eNOS, and nuclear factor E2-related factor 2 (Nrf2), which may protect vascular inflammation caused by HG. In conclusion, APV exerts anti-inflammatory effect via inhibition of ROS/NF-kappaB pathway by inducing HO-1 and eNOS expression mediated by Nrf2, thereby suggesting that Prunella vulgaris may be a possible therapeutic approach to the inhibition of diabetic vascular diseases. PMID- 22312317 TI - The Bridge Helix of RNA polymerase acts as a central nanomechanical switchboard for coordinating catalysis and substrate movement. AB - The availability of in vitro assembly systems to produce recombinant archaeal RNA polymerases (RNAPs) offers one of the most powerful experimental tools for investigating the still relatively poorly understood molecular mechanisms underlying RNAP function. Over the last few years, we pioneered new robot-based high-throughput mutagenesis approaches to study structure/function relationships within various domains surrounding the catalytic center. The Bridge Helix domain, which appears in numerous X-ray structures as a 35-amino-acid-long alpha helix, coordinates the concerted movement of several other domains during catalysis through kinking of two discrete molecular hinges. Mutations affecting these kinking mechanisms have a direct effect on the specific catalytic activity of RNAP and can in some instances more than double it. Molecular dynamics simulations have established themselves as exceptionally useful for providing additional insights and detailed models to explain the underlying structural motions. PMID- 22312318 TI - Structure, Expression, and Function of ICAM-5. AB - Cell adhesion is of utmost importance in normal development and cellular functions. ICAM-5 (intercellular adhesion molecule-5, telencephalin, TLN) is a member of the ICAM family of adhesion proteins. As a novel cell adhesion molecule, ICAM-5 shares many structural similarities with the other members of IgSF, especially the ICAM subgroup; however, ICAM-5 has several unique properties compared to the other ICAMs. With its nine extracellular Ig domains, ICAM-5 is the largest member of ICAM subgroup identified so far. Therefore, it is much more complex than the other ICAMs. The expression of ICAM-5 is confined to the telencephalic neurons of the central nervous system whereas all the other ICAM members are expressed mostly by cells in the immune and blood systems. The developmental appearance of ICAM-5 parallels the time of dendritic elongation and branching, and synapse formation in the telencephalon. As a somatodendrite specific adhesion molecule, ICAM-5 not only participates in immune-nervous system interactions, it could also participate in neuronal activity, Dendrites' targeting signals, and cognition. It would not be surprising if future investigations reveal more binding partners and other related functions of ICAM 5. PMID- 22312319 TI - Mitochondrial DNA Variability within Uromastyx ornata philbyi (Agamidae: Squamata) from Southwestern Saudi Arabia. AB - Approximately 2.4 kbp of mitochondrial DNA was sequenced from 9 individuals of Uromastyx ornata philbyi originating from Taif, Namas, Al-Baha, and Jazan in southwestern Saudi Arabia. The sequenced regions cover eight tRNA genes (tRNA(Gln), tRNA(Ile), tRNA(Met), tRNA(Trp), tRNA(Ala), tRNA(Asn), tRNA(Cys), and tRNA(Tyr)) and two protein-coding genes (NADH dehydrogenase subunit 2 and cytochrome b). U. ornata philbyi had an insertion of 170 bp length between tRNA(Gln) and tRNA(Ile) genes. The first 128 bp of this insertion was similar to the one identified earlier in U. ornata ornata and can be folded into a stem-and loop structure, which was less stable in U. ornata philbyi than in U. ornata ornata, or the second tRNA(Gln) gene. The next 42 bp of the insertion was unique in U. ornata philbyi and additionally retained a stable stem-and-loop structure. Most base substitutions found in the sequenced genes were synonymous transitions rather than transversions. Tree analyses supported the sister group relationship between the two U. ornata subspecies and divided U. ornata philbyi into two groups: Taif+Namas group in the east of Sarawat and Al-Baha+Jazan group in the west of Sarawat. These molecular data are in agreement with current classification of U. ornata. PMID- 22312320 TI - In silico identification and comparative genomics of candidate genes involved in biosynthesis and accumulation of seed oil in plants. AB - Genes involved in fatty acids biosynthesis, modification and oil body formation are expected to be conserved in structure and function in different plant species. However, significant differences in the composition of fatty acids and total oil contents in seeds have been observed in different plant species. Comparative genomics was performed on 261 genes involved in fatty acids biosynthesis, TAG synthesis, and oil bodies formation in Arabidopsis, Brassica rapa, castor bean and soybean. In silico expression analysis revealed that stearoyl desaturase, FatB, FAD2, oleosin and DGAT are highly abundant in seeds, thereby considered as ideal candidates for mining of favorable alleles in natural population. Gene structure analysis for major genes, ACCase, FatA, FatB, FAD2, FAD3 and DGAT, which are known to play crucial role in oil synthesis revealed that there are uncommon variations (SNPs and INDELs) which lead to varying content and composition of fatty acids in seed oil. The predicted variations can provide good targets for seed oil QTL identification, understanding the molecular mechanism of seed oil accumulation, and genetic modification to enhance seed oil yield in plants. PMID- 22312321 TI - Determination of the strength of adhesion between lipid vesicles. AB - A commonly used method to determine the strength of adhesion between adhering lipid vesicles is measuring their effective contact angle from experimental images. The aim of this paper is to estimate the interobserver variations in vesicles effective contact angle measurements and to propose a new method for estimating the strength of membrane vesicle adhesion. Theoretical model shows for the old and for the new measure a monotonic dependence on the strength of adhesion. Results obtained by both measuring techniques show statistically significant correlation and high interobserver reliability for both methods. Therefore the conventional method of measuring the effective contact angle gives qualitatively relevant results as the measure of the lipid vesicle adhesion. However, the new measuring technique provides a lower variation of the measured values than the conventional measures using the effective contact angle. Moreover, obtaining the adhesion angle can be automatized more easily than obtaining the effective contact angle. PMID- 22312323 TI - Nemesia root hair response to paper pulp substrate for micropropagation. AB - Agar substrates for in vitro culture are well adapted to plant micropropagation, but not to plant rooting and acclimatization. Conversely, paper-pulp-based substrates appear as potentially well adapted for in vitro culture and functional root production. To reinforce this hypothesis, this study compares in vitro development of nemesia on several substrates. Strong differences between nemesia roots growing in agar or in paper-pulp substrates were evidenced through scanning electron microscopy. Roots developed in agar have shorter hairs, larger rhizodermal cells, and less organized root caps than those growing on paper pulp. In conclusion, it should be noted that in this study, in vitro microporous substrates such as paper pulp lead to the production of similar root hairs to those found in greenhouse peat substrates. Consequently, if agar could be used for micropropagation, rooting, and plant acclimatization, enhancement could be achieved if rooting stage was performed on micro-porous substrates such as paper pulp. PMID- 22312322 TI - Neurocysticercosis: a review. AB - Neuroysticercosis is the most common helminthic infection of the nervous system, and a leading cause of acquired epilepsy worldwide. The disease occurs when humans become intermediate hosts of Taenia solium by ingesting its eggs from contaminated food or, most often, directly from a taenia carrier by the fecal-to oral route. Cysticerci may be located in brain parenchyma, subarachnoid space, ventricular system, or spinal cord, causing pathological changes that are responsible for the pleomorphism of neurocysticercosis. Seizures are the most common clinical manifestation, but many patients present with focal deficits, intracranial hypertension, or cognitive decline. Accurate diagnosis of neurocysticercosis is possible after interpretation of clinical data together with findings of neuroimaging studies and results of immunological tests. The introduction of cysticidal drugs have changed the prognosis of most patients with neurocysticercosis. These drugs have shown to reduce the burden of infection in the brain and to improve the clinical course of the disease in most patients. Further efforts should be directed to eradicate the disease through the implementation of control programs against all the interrelated steps in the life cycle of T. solium, including human carriers of the adult tapeworm, infected pigs, and eggs in the environment. PMID- 22312324 TI - Nanocrystalline hydroxyapatite/si coating by mechanical alloying technique. AB - A novel approach for depositing hydroxyapatite (HA) films on titanium substrates by using mechanical alloying (MA) technique has been developed. However, it was shown that one-hour heat treatment at 800 degrees C of such mechanically coated HA layer leads to partial transformation of desired HA phase to beta-tri-calcium phosphate (beta-TCP) phase. It appears that the grain boundary and interface defects formed during MA promote this transformation. It was discovered that doping HA by silicon results in hindering this phase transformation process. The Si-doped HA does not show phase transition to beta-TCP or decomposition after heat treatment even at 900 degrees C. PMID- 22312326 TI - Correlations between Different Heavy Metals in Diverse Body Fluids: Studies of Human Semen Quality. AB - It has been hypothesized that exposure to heavy metals may impair male reproduction. To measure the effect produced by low doses of heavy metals on semen parameters, it is necessary to clarify in which body fluids those measurements must be performed. Sixty-one men attending infertility clinics participated in our study. Concentrations of lead, cadmium, and mercury were measured in whole blood, blood plasma, and seminal plasma using spectroanalytical and electrochemical methods. Semen analyses were performed according to World Health Organization criteria. For statistical analysis, Spearman's rank correlations, mean comparison tests, and discriminant analysis were calculated. Significant correlations between the measured concentrations of the three heavy metals in the same biological fluids were observed. However, no similar relationship was seen when comparing the concentrations in different body fluids of the same metal. According to our results and previous publications, seminal plasma might be the best body fluid for assessing impairment of human semen parameters. PMID- 22312325 TI - Differential downregulation of e-cadherin and desmoglein by epidermal growth factor. AB - Modulation of cell : cell junctions is a key event in cutaneous wound repair. In this study we report that activation of the epidermal growth factor (EGF) receptor disrupts cell : cell adhesion, but with different kinetics and fates for the desmosomal cadherin desmoglein and for E-cadherin. Downregulation of desmoglein preceded that of E-cadherin in vivo and in an EGF-stimulated in vitro wound reepithelialization model. Dual immunofluorescence staining revealed that neither E-cadherin nor desmoglein-2 internalized with the EGF receptor, or with one another. In response to EGF, desmoglein-2 entered a recycling compartment based on predominant colocalization with the recycling marker Rab11. In contrast, E-cadherin downregulation was accompanied by cleavage of the extracellular domain. A broad-spectrum matrix metalloproteinase inhibitor protected E-cadherin but not the desmosomal cadherin, desmoglein-2, from EGF-stimulated disruption. These findings demonstrate that although activation of the EGF receptor regulates adherens junction and desmosomal components, this stimulus downregulates associated cadherins through different mechanisms. PMID- 22312328 TI - Mechanisms and implications of age-related changes in the liver. PMID- 22312327 TI - Clinical implications of the transversus abdominis plane block in adults. AB - The transversus abdominis plane (TAP) block is a relatively new regional anesthesia technique that provides analgesia to the parietal peritoneum as well as the skin and muscles of the anterior abdominal wall. It has a high margin of safety and is technically simple to perform, especially under ultrasound guidance. A growing body of evidence supports the use of TAP blocks for a variety of abdominal procedures, yet, widespread adoption of this therapeutic adjunct has been slow. In part, this may be related to the limited sources for anesthesiologists to develop an appreciation for its sound anatomical basis and the versatility of its clinical application. As such, we provide a brief historical perspective on the TAP block, describe relevant anatomy, review current techniques, discuss pharmacologic considerations, and summarize the existing literature regarding its clinical utility with an emphasis on recently published studies that have not been included in other systematic reviews or meta analyses. PMID- 22312329 TI - Fat Modulates the Relationship between Sarcopenia and Physical Function in Nonobese Older Adults. AB - It is intuitive to think that sarcopenia should be associated with declines in physical function though recent evidence questions this assertion. This study investigated the relationship between absolute and relative sarcopenia, with physical performance in 202 nonobese (mean BMI = 26.6 kg/ht(2)) community dwelling older (mean age = 73.8 +/- 5.9 years) adults. While absolute sarcopenia (appendicular skeletal mass (ASM)/ht(2)) was either not associated, or weakly associated with physical performance, relative sarcopenia (ASM/kg) demonstrated moderate (r = 0.31 to r = 0.51, P < 0.01) relationships with performance outcomes in both males and females. Knee extension strength (r = 0.27) and leg extension power (r = 0.41) were both related to absolute sarcopenia (P < 0.001) in females and not in males. Strength and power were associated with relative sarcopenia in both sexes (from r = 0.47 to r = 0.67, P < 0.001). The ratio of lean mass to total body mass, that is, relative sarcopenia, is an important consideration relative to physical function in older adults even in the absence of obesity. Stratifying these individuals into equal tertiles of total body fat revealed a trend of diminished regression coefficients across each incrementally higher fat grouping for performance measures, providing further evidence that total body fat modulates the relationship between sarcopenia and physical function. PMID- 22312330 TI - The Impact of MicroRNAs on Brain Aging and Neurodegeneration. AB - The molecular instructions that govern gene expression regulation are encoded in the genome and ultimately determine the morphology and functional specifications of the human brain. As a consequence, changes in gene expression levels might be directly related to the functional decline associated with brain aging. Small noncoding RNAs, including miRNAs, comprise a group of regulatory molecules that modulate the expression of hundred of genes which play important roles in brain metabolism. Recent comparative studies in humans and nonhuman primates revealed that miRNAs regulate multiple pathways and interconnected signaling cascades that are the basis for the cognitive decline and neurodegenerative disorders during aging. Identifying the roles of miRNAs and their target genes in model organisms combined with system-level studies of the brain would provide more comprehensive understanding of the molecular basis of brain deterioration during the aging process. PMID- 22312331 TI - Inferring Biological Mechanisms by Data-Based Mathematical Modelling: Compartment Specific Gene Activation during Sporulation in Bacillus subtilis as a Test Case. AB - Biological functionality arises from the complex interactions of simple components. Emerging behaviour is difficult to recognize with verbal models alone, and mathematical approaches are important. Even few interacting components can give rise to a wide range of different responses, that is, sustained, transient, oscillatory, switch-like responses, depending on the values of the model parameters. A quantitative comparison of model predictions and experiments is therefore important to distinguish between competing hypotheses and to judge whether a certain regulatory behaviour is at all possible and plausible given the observed type and strengths of interactions and the speed of reactions. Here I will review a detailed model for the transcription factor sigma(F), a regulator of cell differentiation during sporulation in Bacillus subtilis. I will focus in particular on the type of conclusions that can be drawn from detailed, carefully validated models of biological signaling networks. For most systems, such detailed experimental information is currently not available, but accumulating biochemical data through technical advances are likely to enable the detailed modelling of an increasing number of pathways. A major challenge will be the linking of such detailed models and their integration into a multiscale framework to enable their analysis in a larger biological context. PMID- 22312332 TI - Structural Basis for Species Selectivity in the HIV-1 gp120-CD4 Interaction: Restoring Affinity to gp120 in Murine CD4 Mimetic Peptides. AB - The first step of HIV-1 infection involves interaction between the viral glycoprotein gp120 and the human cellular receptor CD4. Inhibition of the gp120 CD4 interaction represents an attractive strategy to block HIV-1 infection. In an attempt to explore the known lack of affinity of murine CD4 to gp120, we have investigated peptides presenting the putative gp120-binding site of murine CD4 (mCD4). Molecular modeling indicates that mCD4 protein cannot bind gp120 due to steric clashes, while the larger conformational flexibility of mCD4 peptides allows an interaction. This finding is confirmed by experimental binding assays, which also evidenced specificity of the peptide-gp120 interaction. Molecular dynamics simulations indicate that the mCD4-peptide stably interacts with gp120 via an intermolecular beta-sheet, while an important salt-bridge formed by a C terminal lysine is lost. Fixation of the C-terminus by introducing a disulfide bridge between the N- and C-termini of the peptide significantly enhanced the affinity to gp120. PMID- 22312333 TI - The paradox of feline coronavirus pathogenesis: a review. AB - Feline coronavirus (FCoV) is an enveloped single-stranded RNA virus, of the family Coronaviridae and the order Nidovirales. FCoV is an important pathogen of wild and domestic cats and can cause a mild or apparently symptomless enteric infection, especially in kittens. FCoV is also associated with a lethal, systemic disease known as feline infectious peritonitis (FIP). Although the precise cause of FIP pathogenesis remains unclear, some hypotheses have been suggested. In this review we present results from different FCoV studies and attempt to elucidate existing theories on the pathogenesis of FCoV infection. PMID- 22312334 TI - Artificial 64-Residue HIV-1 Enhancer-Binding Peptide Is a Potent Inhibitor of Viral Replication in HIV-1-Infected Cells. AB - An artificial HIV-1 enhancer-binding peptide was extended by nine consecutive arginine residues at the C-terminus and by the nuclear localization signal of SV40 large T antigen at the N-terminus. The resulting synthetic 64-residue peptide was found to bind to the two enhancers of the HIV-1 long terminal repeat, cross the plasma membrane and the nuclear envelope of human cells, and suppress the HIV-1 enhancer-controlled expression of a green fluorescent protein reporter gene. Moreover, HIV-1 replication is inhibited by this peptide in HIV-1-infected CEM-GFP cells as revealed by HIV-1 p24 ELISA and real-time RT-PCR of HIV-1 RNA. Rapid uptake of this intracellular stable and inhibitory peptide into the cells implies that this peptide may have the potential to attenuate HIV-1 replication in vivo. PMID- 22312335 TI - Arenavirus budding. AB - Several arenaviruses cause hemorrhagic fever disease in humans and pose a significant public health concern in their endemic regions. On the other hand, the prototypic arenavirus LCMV is a superb workhorse for the investigation of virus-host interactions and associated disease. The arenavirus small RING finger protein called Z has been shown to be the main driving force of virus budding. The budding activity of Z is mediated by late (L) domain motifs, PT/SAP, and PPXY, located at the C-terminus of Z. This paper will present the current knowledge on arenavirus budding including the diversity of L domain motifs used by different arenaviruses. We will also discuss how improved knowledge of arenavirus budding may facilitate the development of novel antiviral strategies to combat human pathogenic arenaviruses. PMID- 22312336 TI - Replication of alphaviruses: a review on the entry process of alphaviruses into cells. AB - Alphaviruses are small, enveloped viruses, ~70 nm in diameter, containing a single-stranded, positive-sense, RNA genome. Viruses belonging to this genus are predominantly arthropod-borne viruses, known to cause disease in humans. Their potential threat to human health was most recently exemplified by the 2005 Chikungunya virus outbreak in La Reunion, highlighting the necessity to understand events in the life-cycle of these medically important human pathogens. The replication and propagation of viruses is dependent on entry into permissive cells. Viral entry is initiated by attachment of virions to cells, leading to internalization, and uncoating to release genetic material for replication and propagation. Studies on alphaviruses have revealed entry via a receptor-mediated, endocytic pathway. In this paper, the different stages of alphavirus entry are examined, with examples from Semliki Forest virus, Sindbis virus, Chikungunya virus, and Venezuelan equine encephalitis virus described. PMID- 22312337 TI - Does Cytomegalovirus Develop Resistance following Antiviral Prophylaxis and Treatment in Renal Transplant Patients in Kuwait? AB - The resistance of cytomegalovirus (CMV) to ganciclovir or valganciclovir is a factor in therapeutic failure and disease progression. CMV strains resistant to ganciclovir or valganciclovir have been associated with specific mutations in the UL97 and UL54 genes. Sequencing of both CMV UL97 and UL54 genes was performed to detect the presence of CMV antiviral resistance in six patients who received ganciclovir (and/or valganciclovir) and had prolonged detectable CMV DNA in their blood during antiviral treatment. Sequencing results showed no specific mutations in either UL97 or UL54 gene of CMV and therefore the CMV strains in kidney transplant patients who received ganciclovir either prophylactically or therapeutically were from the wild type. Our results suggest that CMV management and immunosuppression protocols for kidney transplant patients followed in the Organ Transplant Centre, Kuwait, is very effective in reducing the opportunity of developing CMV antiviral resistance. PMID- 22312338 TI - A systemic network triggered by human cytomegalovirus entry. AB - Virus entry is a multistep process that triggers various cellular pathways that interconnect into a complex network; yet the molecular complexity of this network remains largely elusive. Here, by employing systems biology approaches, we reveal a systemic virus-entry network initiated by human cytomegalovirus (HCMV), a widespread opportunistic pathogen. This network contains ten functional modules (i.e., groups of proteins) that coordinately respond to HCMV entry. Functional modules activated (up- and downregulated) in this network dramatically decline shortly within 25 minutes post infection. While modules annotated as receptor system, ion transport, and immune response are continuously activated during the entire process of HCMV entry, those annotated for cell adhesion and skeletal movement are specifically activated during viral early attachment. The up regulated network contains various functional modules, such as cell surface receptors, skeletal development, endocytosis, ion transport, and chromatin remodeling. Interestingly, macromolecule metabolism and chromatin remodeling module predominates this over-expressed system, suggesting that the fundamental nuclear process modulation is one of the most important events in HCMV entry. The entire up-regulated network is primarily controlled by multiple elements like SLC10A1. Thus, virus entry triggers multiple cellular processes especially nuclear processes to facilitate its entry. PMID- 22312339 TI - Nucleic Acid, Antibody, and Virus Culture Methods to Detect Xenotropic MLV Related Virus in Human Blood Samples. AB - The MLV-related retrovirus, XMRV, was recently identified and reported to be associated with both prostate cancer and chronic fatigue syndrome. At the National Cancer Institute-Frederick, MD (NCI-Frederick), we developed highly sensitive methods to detect XMRV nucleic acids, antibodies, and replication competent virus. Analysis of XMRV-spiked samples and/or specimens from two pigtail macaques experimentally inoculated with 22Rv1 cell-derived XMRV confirmed the ability of the assays used to detect XMRV RNA and DNA, and culture isolatable virus when present, along with XMRV reactive antibody responses. Using these assays, we did not detect evidence of XMRV in blood samples (N = 134) or prostate specimens (N = 19) from two independent cohorts of patients with prostate cancer. Previous studies detected XMRV in prostate tissues. In the present study, we primarily investigated the levels of XMRV in blood plasma samples collected from patients with prostate cancer. These results demonstrate that while XMRV-related assays developed at the NCI-Frederick can readily measure XMRV nucleic acids, antibodies, and replication competent virus, no evidence of XMRV was found in the blood of patients with prostate cancer. PMID- 22312340 TI - Testing strategies for detection of xenotropic murine leukemia virus-related virus infection. AB - Xenotropic murine leukemia virus-related virus (XMRV) is a newly identified gamma retrovirus and may be associated with prostate cancer- (PC) and chronic fatigue syndrome (CFS). Since its identification in 2006 and detection of polytropic murine lenkemia virus (MLV)-like sequences in CFS patients in 2010, several test methods including nucleic acid testing methods and serological assays have been developed for detection of XMRV and/or MLV-like sequences. However, these research assays have not yet been validated and evaluated due to the lack of well characterized reference materials. Mouse DNA contamination should be carefully checked when testing human specimens in order to avoid false-positive detection of XMRV or MLV-like sequences. PMID- 22312341 TI - Association of influenza virus proteins with membrane rafts. AB - Assembly and budding of influenza virus proceeds in the viral budozone, a domain in the plasma membrane with characteristics of cholesterol/sphingolipid-rich membrane rafts. The viral transmembrane glycoproteins hemagglutinin (HA) and neuraminidase (NA) are intrinsically targeted to these domains, while M2 is seemingly targeted to the edge of the budozone. Virus assembly is orchestrated by the matrix protein M1, binding to all viral components and the membrane. Budding progresses by protein- and lipid-mediated membrane bending and particle scission probably mediated by M2. Here, we summarize the experimental evidence for this model with emphasis on the raft-targeting features of HA, NA, and M2 and review the functional importance of raft domains for viral protein transport, assembly and budding, environmental stability, and membrane fusion. PMID- 22312342 TI - Murine leukemia viruses: objects and organisms. AB - Murine leukemia viruses (MLVs) are among the simplest retroviruses. Prototypical gammaretroviruses encode only the three polyproteins that will be used in the assembly of progeny virus particles. These are the Gag polyprotein, which is the structural protein of a retrovirus particle, the Pol protein, comprising the three retroviral enzymes-protease, which catalyzes the maturation of the particle, reverse transcriptase, which copies the viral RNA into DNA upon infection of a new host cell, and integrase, which inserts the DNA into the chromosomal DNA of the host cell, and the Env polyprotein, which induces the fusion of the viral membrane with that of the new host cell, initiating infection. In general, a productive MLV infection has no obvious effect upon host cells. Although gammaretroviral structure and replication follow the same broad outlines as those of other retroviruses, we point out a number of significant differences between different retroviral genera. PMID- 22312344 TI - Internally controlled, generic real-time PCR for quantification and multiplex real-time PCR with serotype-specific probes for serotyping of dengue virus infections. AB - Dengue has become a global public health problem and a sensitive diagnostic test for early phase detection can be life saving. An internally controlled, generic real-time PCR was developed and validated by testing serial dilutions of a DENV positive control RNA in the presence of a fixed amount of IC with results showing a good linearity (R(2) = 0.9967) and a LOD of at least 1.95 * 10(4) copies/mL. Application of the generic PCR on 136 patient samples revealed a sensitivity of 95.8% and specificity of 100%. A newly developed multiplex real-time PCR with serotype-specific probes allowed the serotyping of DENV for 80 out of 92 (87%) generic real-time PCR positive patients. Combined these real-time PCRs offer a convenient diagnostic tool for the sensitive and specific quantification of DENV in clinical specimens with the possibility for serotyping. PMID- 22312343 TI - XMRV Discovery and Prostate Cancer-Related Research. AB - Xenotropic murine leukemia virus-related virus (XMRV) was first reported in 2006 in a study of human prostate cancer patients with genetic variants of the antiviral enzyme, RNase L. Subsequent investigations in North America, Europe, Asia, and Africa have either observed or failed to detect XMRV in patients (prostate cancer, chronic fatigue syndrome-myalgic encephalomyelitis (CFS-ME), and immunosuppressed with respiratory tract infections) or normal, healthy, control individuals. The principal confounding factors are the near ubiquitous presence of mouse-derived reagents, antibodies and cells, and often XMRV itself, in laboratories. XMRV infects and replicates well in many human cell lines, but especially in certain prostate cancer cell lines. XMRV also traffics to prostate in a nonhuman primate model of infection. Here, we will review the discovery of XMRV and then focus on prostate cancer-related research involving this intriguing virus. PMID- 22312345 TI - Imaging early steps of sindbis virus infection by total internal reflection fluorescence microscopy. AB - Sindbis virus (SINV) is an alphavirus that has a broad host range and has been widely used as a vector for recombinant gene transduction, DNA-based vaccine production, and oncolytic cancer therapy. The mechanism of SINV entry into host cells has yet to be fully understood. In this paper, we used single virus tracking under total internal reflection fluorescence microscopy (TIRFM) to investigate SINV attachment to cell surface. Biotinylated viral particles were labeled with quantum dots, which retained viral viability and infectivity. By time-lapse imaging, we showed that the SINV exhibited a heterogeneous dynamics on the surface of the host cells. Analysis of SINV motility demonstrated a two-step attachment reaction. Moreover, dual color TIRFM of GFP-Rab5 and SINV suggested that the virus was targeted to the early endosomes after endocytosis. These findings demonstrate the utility of quantum dot labeling in studying the early steps and behavior of SINV infection. PMID- 22312346 TI - Antiviral and virucidal activities of nalpha-cocoyl-L-arginine ethyl ester. AB - Various amino acid-derived compounds, for example, Nalpha-Cocoyl-L-arginine ethyl ester (CAE), alkyloxyhydroxylpropylarginine, arginine cocoate, and cocoyl glycine potassium salt (Amilite), were examined for their virucidal activities against herpes simplex virus type 1 and 2 (HSV-1 and HSV-2), influenza A virus (IAV), and poliovirus type 1 (PV-1) in comparison to benzalkonium chloride (BKC) and sodium dodecylsulfate (SDS) as a cationic and anionic control detergent and also to other commercially available disinfectants. While these amino acid-derived compounds were all effective against HSV-1 and HSV-2, CAE and Amilite were the most effective. These two compounds were, however, not as effective against IAV, another enveloped virus, as against HSV. Cytotoxicity of CAE was weak; at 0.012%, only 5% of the cells were killed under the conditions, in which 100% cells were killed by either SDS or BKC. In addition to these direct virucidal effects, CAE inhibited the virus growth in the HSV-1- or PV-1-infected cells even at 0.01%. These results suggest a potential application of CAE as a therapeutic or preventive medicine against HSV superficial infection at body surface. PMID- 22312347 TI - Feline and canine coronaviruses: common genetic and pathobiological features. AB - A new human coronavirus responsible for severe acute respiratory syndrome (SARS) was identified in 2003, which raised concern about coronaviruses as agents of serious infectious disease. Nevertheless, coronaviruses have been known for about 50 years to be major agents of respiratory, enteric, or systemic infections of domestic and companion animals. Feline and canine coronaviruses are widespread among dog and cat populations, sometimes leading to the fatal diseases known as feline infectious peritonitis (FIP) and pantropic canine coronavirus infection in cats and dogs, respectively. In this paper, different aspects of the genetics, host cell tropism, and pathogenesis of the feline and canine coronaviruses (FCoV and CCoV) will be discussed, with a view to illustrating how study of FCoVs and CCoVs can improve our general understanding of the pathobiology of coronaviruses. PMID- 22312348 TI - The Prevalence of STIV c92-Like Proteins in Acidic Thermal Environments. AB - A new type of viral-induced lysis system has recently been discovered for two unrelated archaeal viruses, STIV and SIRV2. Prior to the lysis of the infected host cell, unique pyramid-like lysis structures are formed on the cell surface by the protrusion of the underlying cell membrane through the overlying external S layer. It is through these pyramid structures that assembled virions are released during lysis. The STIV viral protein c92 is responsible for the formation of these lysis structures. We searched for c92-like proteins in viral sequences present in multiple viral and cellular metagenomic libraries from Yellowstone National Park acidic hot spring environments. Phylogenetic analysis of these proteins demonstrates that, although c92-like proteins are detected in these environments, some are quite divergent and may represent new viral families. We hypothesize that this new viral lysis system is common within diverse archaeal viral populations found within acidic hot springs. PMID- 22312350 TI - Bacterial Toxin Fusion Proteins Elicit Mucosal Immunity against a Foot-and-Mouth Disease Virus Antigen When Administered Intranasally to Guinea Pigs. AB - Peptides corresponding to the foot-and-mouth disease virus VP1 G-H loop are capable of inducing neutralizing antibodies in some species but are considered relatively poor immunogens, especially at mucosal surfaces. However, intranasal administration of antigens along with the appropriate delivery vehicle/adjuvant has been shown to induce mucosal immune responses, and bacterial enterotoxins have long been known to be effective in this regard. In the current study, two different carrier/adjuvant approaches were used to augment mucosal immunity to the FMDV O(1) BFS G-H loop epitope, in which the G-H loop was genetically coupled to the E. coli LT-B subunit and coexpressed with the LTA2 fragment (LTA2B-GH), or the nontoxic pseudomonas exotoxin A (ntPE) was fused to LTA2B-GH at LT-A2 to enhance receptor targeting. Only guinea pigs that were inoculated intranasally with ntPE-LTA2B-GH and LTA2B-GH induced significant anti-G-H loop IgA antibodies in nasal washes at weeks 4 and 6 when compared to ovalbumin or G-H loop immunized animals. These were also the only groups that exhibited G-H loop-specific antigen secreting cells in the nasal mucosa. These data demonstrate that fusion of nonreplicating antigens to LTA2B and ntPE-LTA2B has the potential to be used as carriers/adjuvants to induce mucosal immune responses against infectious diseases. PMID- 22312349 TI - The Role of Plasmacytoid Dendritic Cells in Innate and Adaptive Immune Responses against Alpha Herpes Virus Infections. AB - In 1999, two independent groups identified plasmacytoid dendritic cells (PDC) as major type I interferon- (IFN-) producing cells in the blood. Since then, evidence is accumulating that PDC are a multifunctional cell population effectively coordinating innate and adaptive immune responses. This paper focuses on the role of different immune cells and their interactions in the surveillance of alpha herpes virus infections, summarizes current knowledge on PDC surface receptors and their role in direct cell-cell contacts, and develops a risk factor model for the clinical implications of herpes simplex and varicella zoster virus reactivation. Data from studies involving knockout mice and cell-depletion experiments as well as human studies converge into a "spider web", in which the direct and indirect crosstalk between many cell populations tightly controls acute, latent, and recurrent alpha herpes virus infections. Notably, cells involved in innate immune regulations appear to shape adaptive immune responses more extensively than previously thought. PMID- 22312351 TI - The Effects of Temperature and Relative Humidity on the Viability of the SARS Coronavirus. AB - The main route of transmission of SARS CoV infection is presumed to be respiratory droplets. However the virus is also detectable in other body fluids and excreta. The stability of the virus at different temperatures and relative humidity on smooth surfaces were studied. The dried virus on smooth surfaces retained its viability for over 5 days at temperatures of 22-25 degrees C and relative humidity of 40-50%, that is, typical air-conditioned environments. However, virus viability was rapidly lost (>3 log(10)) at higher temperatures and higher relative humidity (e.g., 38 degrees C, and relative humidity of >95%). The better stability of SARS coronavirus at low temperature and low humidity environment may facilitate its transmission in community in subtropical area (such as Hong Kong) during the spring and in air-conditioned environments. It may also explain why some Asian countries in tropical area (such as Malaysia, Indonesia or Thailand) with high temperature and high relative humidity environment did not have major community outbreaks of SARS. PMID- 22312352 TI - No Evidence of XMRV or MuLV Sequences in Prostate Cancer, Diffuse Large B-Cell Lymphoma, or the UK Blood Donor Population. AB - Xenotropic murine leukaemia virus-related virus (XMRV) is a recently described retrovirus which has been claimed to infect humans and cause associated pathology. Initially identified in the US in patients with prostate cancer and subsequently in patients with chronic fatigue syndrome, doubt now exists that XMRV is a human pathogen. We studied the prevalence of genetic sequences of XMRV and related MuLV sequences in human prostate cancer, from B cell lymphoma patients and from UK blood donors. Nucleic acid was extracted from fresh prostate tissue biopsies, formalin-fixed paraffin-embedded (FFPE) prostate tissue and FFPE B-cell lymphoma. The presence of XMRV-specific LTR or MuLV generic gag-like sequences was investigated by nested PCR. To control for mouse DNA contamination, a PCR that detected intracisternal A-type particle (IAP) sequences was included. In addition, DNA and RNA were extracted from whole blood taken from UK blood donors and screened for XMRV sequences by real-time PCR. XMRV or MuLV-like sequences were not amplified from tissue samples. Occasionally MuLV gag and XMRV LTR sequences were amplified from Indian prostate cancer samples, but were always detected in conjunction with contaminating murine genomic DNA. We found no evidence of XMRV or MuLV infection in the UK blood donors. PMID- 22312353 TI - Xenotropic and other murine leukemia virus-related viruses in humans. PMID- 22312354 TI - Lack of Detection of Xenotropic Murine Leukemia Virus-Related Virus in HIV-1 Lymphoma Patients. AB - Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus reported to be associated with human prostate cancer and chronic fatigue syndrome. Since retroviruses cause various cancers, and XMRV replication might be facilitated by HIV-1 co-infection, we asked whether certain patients with HIV associated lymphomas are infected with XMRV. Analysis of PMBCs and plasma from 26 patients failed to detect XMRV by PCR, ELISA, or Western blot, suggesting a lack of association between XMRV and AIDS-associated lymphomas. PMID- 22312355 TI - MoMuLV-ts-1: A Unique Mouse Model of Retrovirus-Induced Lymphoma Transmitted by Breast Milk. AB - Our laboratory has developed a murine model of lymphoma via breast milk transmission of MoMuLV-ts-1 (Moloney murine leukemia virus-temperature sensitive mutant-1). Uninfected offspring suckled from infected surrogate mothers become infected and develop lymphoma. Multiple gene integration sites of ts-1 into the infected mouse genome including tacc3, aurka, ndel1, tpx2, p53, and rhamm were identified, and mRNA expressions were quantitated. These genes produce centrosomal proteins, which may be involved in abnormal chromosomal segregation leading to aneuploidy or multiploidy, thus causing lymphoma. Since there is no report to date on this retroviral model leading to centrosomal abnormality, and causing lymphoma development, this is a valuable and unique model to study the centrosomal involvement in lymphomagenesis. PMID- 22312356 TI - Failure to Detect XMRV-Specific Antibodies in the Plasma of CFS Patients Using Highly Sensitive Chemiluminescence Immunoassays. AB - In 2009, Lombardi et al. reported their startling finding that the gammaretrovirus xenotropic murine leukemia virus-related retrovirus (XMRV) is present in 67% of blood samples of patients suffering from chronic fatigue syndrome (CFS), as opposed to only 3.7% of samples from healthy individuals. However, we and others could not confirm these results, using a nested PCR assay. An alternative to this highly sensitive, but contamination-prone, technique is to measure the serological response to XMRV. Thus, we tested the plasma samples from our cohorts of CFS patients and healthy controls for the presence of XMRV specific antibodies. Using two novel chemiluminescence immunoassays (CMIAs), we show that none of our samples have any XMRV-reactive antibodies. Taken together with our previous findings, we conclude that XMRV is not present in any human individual tested by us, regardless of CFS or healthy control. PMID- 22312357 TI - Perspective: emerging challenges in the treatment of influenza and parainfluenza in transplant patients. AB - Influenza, respiratory synctial virus, and parainfluenza are common respiratory infections in immunocompromised transplant recipients, causing significant morbidity and mortality in this patient population. This paper focuses on influenza and parainfluenza virus infections in transplant patients with emphasis on the pandemic 2009 H1N1 influenza infection. Current antiviral treatment recommendations for influenza and parainfluenza in immunocompromised patients as well as novel investigational therapeutic approaches currently being tested in the clinic are discussed. In addition to the morbidity and mortality caused by these viruses, the development of multidrug resistance leading to transmission of resistant viruses is of great public health concern. The development of effective new therapies for influenza and parainfluenza in these high-risk patients is needed with randomized placebo-controlled studies to assess their clinical utility. PMID- 22312358 TI - Endogenous Murine Leukemia Viruses: Relationship to XMRV and Related Sequences Detected in Human DNA Samples. AB - Xenotropic-murine-leukemia-virus-related virus (XMRV) was the first gammaretrovirus to be reported in humans. The sequence similarity between XMRV and murine leukemia viruses (MLVs) was consistent with an origin of XMRV from one or more MLVs present as endogenous proviruses in mouse genomes. Here, we review the relationship of the human and mouse virus isolates and discuss the potential complications associated with the detection of MLV-like sequences from clinical samples. PMID- 22312359 TI - Virus budding/host interactions. PMID- 22312360 TI - Sexual Transmission of XMRV: A Potential Infection Route. AB - Although XMRV dissemination in humans is a matter of debate, the prostate of select patients seem to harbor XMRV, which raises questions about its potential route of transmission. We established a model of infection in rhesus macaques inoculated with XMRV. In spite of the intravenous inoculation, all infected macaques exhibited readily detectable XMRV signal in the reproductive tract of all 4 males and 1 female during both acute and chronic infection stages. XMRV showed explosive growth in the acini of prostate during acute but not chronic infection. In seminal vesicles, epididymis, and testes, XMRV protein production was detected throughout infection in interstitial or epithelial cells. In the female monkey, epithelial cells in the cervix and vagina were also positive for XMRV gag. The ready detection of XMRV in the reproductive tract of male and female macaques infected intravenously suggests the potential for sexual transmission for XMRV. PMID- 22312362 TI - Oncolytic virotherapy for hematological malignancies. AB - Hematological malignancies such as leukemias, lymphomas, multiple myeloma (MM), and the myelodysplastic syndromes (MDSs) primarily affect adults and are difficult to treat. For high-risk disease, hematopoietic stem cell transplant (HCT) can be used. However, in the setting of autologous HCT, relapse due to contamination of the autograft with cancer cells remains a major challenge. Ex vivo manipulations of the autograft to purge cancer cells using chemotherapies and toxins have been attempted. Because these past strategies lack specificity for malignant cells and often impair the normal hematopoietic stem and progenitor cells, prior efforts to ex vivo purge autografts have resulted in prolonged cytopenias and graft failure. The ideal ex vivo purging agent would selectively target the contaminating cancer cells while spare normal stem and progenitor cells and would be applied quickly without toxicities to the recipient. One agent which meets these criteria is oncolytic viruses. This paper details experimental progress with reovirus, myxoma virus, measles virus, vesicular stomatitis virus, coxsackievirus, and vaccinia virus as well as requirements for translation of these results to the clinic. PMID- 22312361 TI - Naturally Occurring Polymorphisms of the Mouse Gammaretrovirus Receptors CAT-1 and XPR1 Alter Virus Tropism and Pathogenicity. AB - Gammaretroviruses of several different host range subgroups have been isolated from laboratory mice. The ecotropic viruses infect mouse cells and rely on the host CAT-1 receptor. The xenotropic/polytropic viruses, and the related human derived XMRV, can infect cells of other mammalian species and use the XPR1 receptor for entry. The coevolution of these viruses and their receptors in infected mouse populations provides a good example of how genetic conflicts can drive diversifying selection. Genetic and epigenetic variations in the virus envelope glycoproteins can result in altered host range and pathogenicity, and changes in the virus binding sites of the receptors are responsible for host restrictions that reduce virus entry or block it altogether. These battleground regions are marked by mutational changes that have produced 2 functionally distinct variants of the CAT-1 receptor and 5 variants of the XPR1 receptor in mice, as well as a diverse set of infectious viruses, and several endogenous retroviruses coopted by the host to interfere with entry. PMID- 22312363 TI - Oncolytic viruses: the power of directed evolution. AB - Attempts at developing oncolytic viruses have been primarily based on rational design. However, this approach has been met with limited success. An alternative approach employs directed evolution as a means of producing highly selective and potent anticancer viruses. In this method, diverse viruses are grown under conditions that maximize diversity and then passaged under conditions meant to mimic those encountered in the human cancer microenvironment. Viruses which evolve to thrive under this selective pressure are isolated and tested to identify those with increased potency (i.e., ability to replicate and spread) and/or an increased therapeutic window (i.e., differentiated replication and spread on tumor versus normal cells), both of which have potential value but the latter of which defines an oncolytic virus. Using ColoAd1, an oncolytic virus derived by this approach as a prototype, we highlight the benefits of directed evolution, discuss methods to "arm" these novel viruses, and introduce techniques for their genetic modulation and control. PMID- 22312364 TI - Deciphering the Multifaceted Relationship between Oncolytic Viruses and Natural Killer Cells. AB - Despite active research in virotherapy, this apparently safe modality has not achieved widespread success. The immune response to viral infection appears to be an essential factor that determines the efficacy of oncolytic viral therapy. The challenge is determining whether the viral-elicited immune response is a hindrance or a tool for viral treatment. NK cells are a key component of innate immunity that mediates antiviral immunity while also coordinating tumor clearance. Various reports have suggested that the NK response to oncolytic viral therapy is a critical factor in premature viral clearance while also mediating downstream antitumor immunity. As a result, particular attention should be given to the NK cell response to various oncolytic viral vectors and how their antiviral properties can be suppressed while maintaining tumor clearance. In this review we discuss the current literature on the NK response to oncolytic viral infection and how future studies clarify this intricate response. PMID- 22312365 TI - Retargeting of viruses to generate oncolytic agents. AB - Oncolytic virus therapy is based on the ability of viruses to effectively infect and kill tumor cells without destroying the normal tissues. While some viruses seem to have a natural preference for tumor cells, most viruses require the modification of their tropism to specifically enter and replicate in such cells. This review aims to describe the transductional targeting strategies currently employed to specifically redirect viruses towards surface receptors on tumor cells. Three major strategies can be distinguished; they involve (i) the incorporation of new targeting specificity into a viral surface protein, (ii) the incorporation of a scaffold into a viral surface protein to allow the attachment of targeting moieties, and (iii) the use of bispecific adapters to mediate targeting of a virus to a specified moiety on a tumor cell. Of each strategy key features, advantages and limitations are discussed and examples are given. Because of their potential to cause sustained, multiround infection-a desirable characteristic for eradicating tumors-particular attention is given to viruses engineered to become self-targeted by the genomic expression of a bispecific adapter protein. PMID- 22312366 TI - The role of autologous stem cell transplantation in the treatment of diffuse large B-cell lymphoma. AB - Diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) accounting for approximately 30% of new lymphoma diagnoses in adult patients. Complete remissions (CRs) can be achieved in 45% to 55% of patients and cure in approximately 30-35% with anthracycline-containing combination chemotherapy. The ageadjusted IPI (aaIPI) has been widely employed, particularly to "tailor" more intensive therapy such as high-dose therapy (HDT) with autologous hemopoietic stem cell rescue (ASCT). IPI, however, has failed to reliably predict response to specific therapies. A subgroup of young patients with poor prognosis exists. To clarify the role of HDT/ASCT combined with rituximab in the front line therapy a longer follow-up and randomized studies are needed. The benefit of HDT/ASCT for refractory or relapsed DLBCL is restricted to patients with immunochemosensitive disease. Currently, clinical and biological research is focused to improve the curability of this setting of patients, mainly young. PMID- 22312367 TI - Nonengraftment haploidentical cellular therapy for hematologic malignancies. AB - Much of the therapeutic benefit of allogeneic transplant is by a graft versus tumor effect. Further data shows that transplant engraftment is not dependant on myeloablation, instead relying on quantitative competition between donor and host cells. In the clinical setting, engraftment by competition alone is not feasible due to the need for large numbers of infused cells. Instead, low-level host irradiation has proven to be an effective engraftment strategy that is stem cell toxic but not myeloablative. The above observations served as the foundation for clinical trials utilizing allogeneic matched and haploidentical peripheral blood stem cell infusions with minimal conditioning in patients with refractory malignancies. Although engraftment was transient or not apparent, there were compelling responses in a heavily pretreated patient population that appear to result from the breaking of tumor immune tolerance by the host through the actions of IFNgamma, invariant NK T cells, CD8 T cells, NK cells, or antigen presenting cells. PMID- 22312368 TI - Ewing sarcoma/primitive neuroectodermal tumor of the kidney: two unusual presentations of a rare tumor. AB - Only few cases of primary renal Ewing's sarcoma have been reported in the literature to date. We present here two cases of renal ES/PNET with an uncanny presentation. The first case was discovered after the patient presented clinically with irradiating flank pain, mimicking the pain related with kidney stones. The second case had clinical presentation of pulmonary thromboembolism after the patient was involved in an automobilist accident. The tumors were mainly composed of small blue cells which by immunohistochemical were positive for neural markers, and FISH revealed the translocation 22q12 for the EWSR1 gene. The diagnosis of renal primitive neuroectodermal tumor/EWING tumor is very rare and usually involves several different diagnostic techniques. The differential diagnosis is usually broad with frequent overlapping features between the entities. The cases presented in this paper illustrated the difficulties with which routine anatomical pathologist is faced when dealing with rare renal poorly differentiated neoplasm in adults. PMID- 22312369 TI - PTLD Burkitt Lymphoma in a Patient with Remote Lymphomatoid Granulomatosis. AB - Posttransplant lymphoproliferative disorder (PTLD) is a potentially fatal complication of solid organ transplantation. The majority of PTLD is of B-cell origin, and 90% are associated with the Epstein-Barr virus (EBV). Lymphomatoid granulomatosis (LG) is a rare, EBV-associated systemic angiodestructive lymphoproliferative disorder, which has rarely been described in patients with renal transplantation. We report the case of a patient with renal transplantation for SLE, who presented, 9 months after renal transplantation, an EBV-associated LG limited to the intracranial structures that recovered completely after adjustment of her immunosuppressive treatment. Nine years later, she developed a second PTLD disorder with central nervous system initial manifestation. Workup revealed an EBV-positive PTLD Burkitt lymphoma, widely disseminated in most organs. In summary, the reported patient presented two lymphoproliferative disorders (LG and Burkitt's lymphoma), both with initial neurological manifestation, at 9 years interval. With careful reduction of the immunosuppression after the first manifestation and with the use of chemotherapy combined with radiotherapy after the second manifestation, our patient showed complete disappearance of neurologic symptoms and she is clinically well with good kidney function. No recurrence has been observed by radiological imaging until now. PMID- 22312370 TI - Policy for prevention of a retained sponge after vaginal delivery. AB - Background. Policies for sponge count are not routine practice in most labor and delivery rooms. Ignored or hidden retained vaginal foreign bodies has potentially significant health care morbidity. Case. This was a case of a retained vaginal sponge following an uncomplicated spontaneous vaginal delivery. Delivery room policy resulted in the discovery of the sponge on X-ray when an incorrect sponge count occurred and physical exam did not find the sponge. Conclusion. This emphasizes the use of protocols to enhance patient safety and prevent medical error. PMID- 22312371 TI - A case of persistent foot pain in a neurofibromatosis type I patient. AB - Introduction. This is the case of a young male patient who presented to his family physician with atypical left foot pain, which was extremely resistant to analgesia and caused significant disability. Despite extensive investigations, the cause of his pain was not identified until 18 months after his initial symptoms, when the official diagnosis of malignant peripheral nerve sheath tumour (MPNST) was made. Detailed review of the patient's past history established the diagnosis of type I neurofibromatosis (NF-1), previously undetected. Discussion. NF-1 is an autosomal dominant genetic disorder caused by loss of function mutations of the NF1 gene in chromosome 17. Patients with this condition are at increased risk for developing MPNSTs which, however, are treatable only in early stages. Conclusion. Although monitoring NF-1 patients for the development of MPNSTs is common practice, the index of clinical suspicion in patients without an established NF-1 diagnosis is low. Any atypical pain in young adults should raise the possibility of this malignancy, and this case illustrates the fact that MPNSTs can be the first manifestation of NF-1 in patients previously undiagnosed with the disease. PMID- 22312372 TI - Dynamic Magnetic Resonance Imaging Demonstrates the Integrity of Perineal Reconstruction following Cylindrical Abdominoperineal Excision with Reconstruction of the Pelvic Floor Using Porcine Collagen. AB - A 72-year-old female presented with a six-month history of increased frequency of defecation, rectal bleeding, and severe rectal pain. Digital rectal examination and endoscopy revealed a low rectal lesion lying anteriorly. This was confirmed histologically as adenocarcinoma. Radiological staging was consistent with a T(3)N(2) rectal tumour. Following long-course chemoradiotherapy repeat staging did not identify any metastatic disease. She underwent a laparoscopic cylindrical abdominoperineal excision with en bloc resection of the coccyx and posterior wall of the vagina with a negative circumferential resection margin. The perineal defect was reconstructed with Permacol (biological implant, Covidien) mesh. She had no clinical evidence of a perineal hernia at serial followup. Dynamic MRI images of the pelvic floor obtained during valsalva at 10 months revealed an intact pelvic floor. A control case that had undergone a conventional abdominoperineal excision with primary perineal closure without clinical evidence of herniation was also imaged. This confirmed subclinical perineal herniation with significant downward migration of the bowel and bladder below the pubococcygeal line. We eagerly await further evidence supporting a role for dynamic MR imaging in assessing the integrity of a reconstructed pelvic floor following cylindrical abdominoperineal excision. PMID- 22312373 TI - The influence of high-dose simvastatin and diltiazem on myocardium in rabbits: a haemodynamic study. AB - INTRODUCTION: Simvastatin and diltiazem are often prescribed together for the treatment of hypercholesterolaemia in patients with hypertension and/or angina pectoris. However, diltiazem, a CYP3A inhibitor, is a well-recognized risk factor of skeletal muscle myopathy. It is not known whether such interaction also affects myocardial efficiency causing haemodynamic changes. The aim of the experiment was to establish the impact of simvastatin co-administered with diltiazem on the haemodynamic parameters after continuous infusion of dopamine. MATERIAL AND METHODS: The experiments were performed on 28 New Zealand white rabbits. The animals were divided into four groups receiving: 0.2% MC - methylcellulose (control group); diltiazem; simvastatin; simvastatin + diltiazem, for 14 days (po). The following haemodynamic parameters were estimated: cardiac output index (CI), heart rate (HR), systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP) and total peripheral resistance index (TPRI). The registration of haemodynamic parameters was performed by the Doppler method and during the experiments the animals were anaesthetized with alpha-chloralose (75 mg/kg bw) and urethane (500 mg/kg bw). RESULTS: Dopamine did not cause a statistically significant increase in CI in rabbits receiving simvastatin alone. Diltiazem significantly increased CI if given simultaneously with simvastatin, which might suggest the improvement of cardiac efficiency resulting from such interaction. CONCLUSIONS: The possibility of another mechanism of drug-drug interaction than the one based on CYP3A inhibition, and its impact on cardiac or skeletal muscle, might be considered. PMID- 22312374 TI - The protective effects of Ambroxol in Pseudomonas aeruginosa-induced pneumonia in rats. AB - INTRODUCTION: To evaluate the effect of Ambroxol on the pulmonary surfactant (PS) in rat pneumonia induced by Pseudomonas aeruginosa (PA). MATERIAL AND METHODS: The pneumonic rats were obtained by injecting ATCC27853 intratracheally. One hundred and twenty SD rats were randomized into four groups: normal saline and Ambroxol was injected intraperitoneally following PA challenge in the PA/NS and PA/AM group; the other two groups were NS/AM and NS/NS. The wet/dry weight ratio (W/D), and pathological changes were assayed. Total proteins (TP), total phospholipid (TPL), and dipalmitoylphosphatidylcholine (DPPC) in bronchial alveolar lavage fluid (BALF) were analysed. Some BALF was cultured for colony counts. Ultrastructural change of the lung was observed by electron microscopy. RESULTS: The W/D ratio in the PA/AM group was lower than that in the PA/NS group; both were higher than that in the NS/NS group (p < 0.05). There were more neutrophils in the PA/NS group than in the PA/AM group (p < 0.05), and more in the PA/AM group than in the NS/NS group (p < 0.05). The ratio of DSPC/TPL and DSPC/TP in the BALF in PA/NS group was lower than that in the PA/AM group; DSPC/TPL and DSPC/TP ratios also increased in the NS/AM group. The PA colony numbers in the PA/AM group were lower than in the PA/NS group (p > 0.05). In the PA/NS group, vacuolation occurred in the lamellar body of alveolar type 2 cells (AT2) and the PS layer was rough and broken in some areas. In the PA/AM group, the degree of vacuolation of the lamellar body was less than in the PA/NS group. CONCLUSIONS: Ambroxol could protect rats from pneumonia by improving the level of endogenous PS, especially DPPC. PMID- 22312375 TI - Giant coronary sinus aneurysm secondary to right coronary arteriovenous fistula leading to pseudo-mitral stenosis. AB - We herein report a case in which a right coronary to coronary sinus arteriovenous fistula determined progressive aneurysmatic dilatation of the coronary sinus. Severe compression of the left atrium ensued. This led to a clinical and instrumental picture similar to that observed in severe mitral stenosis. PMID- 22312376 TI - Hepatitis and the polyglandular autoimmune syndrome, type 1. AB - Autoimmune polyglandular syndrome, type 1 (APS-1) is a rare syndrome. Here we present a case report of a 24-year-old female patient who complained of progressive weakness. While autoimmune hepatitis was diagnosed, no improvement of biochemical parameters was obtained after immunosuppressive treatment. Hypoparathyroidism and adrenocortical failure were identified. Her health status clearly improved once proper control of the calcium-phosphate metabolism was obtained and after the administration of substitution hydrocortisone doses, leading to full normalization of biochemical liver tests. The reported case illustrates a rare form of APS-1 failure, in which the diagnosed autoimmune hepatitis was only the first symptom. PMID- 22312377 TI - Unthought-of problems regarding hepatitis D virus infection. AB - In this editorial I will present some unanswered questions about hepatitis D virus (HDV) infection and some further discussion; everybody is asked to send us their comments. PMID- 22312378 TI - Genotyping and infection rate of GBV-C among Iranian HCV- infected patients. AB - BACKGROUND AND AIMS: Hepatitis G virus/GB virus-C (HGV/GBV-C) is a newly identified member of the Flaviviridae family. Its clinical significance in chronic hepatitis C infection remains controversial. There is a geographical difference in the distribution of GBV-C in the world. The frequency of GBV-C infection among hepatitis C virus (HCV) infected patients varies. The aim of the current study was to determine the prevalence and genotypes of GBV-C among Iranian patients infected with chronic HCV. METHODS: Infection with GBV-C was surveyed in 71 chronic confirmed hepatitis C infected patients. These samples were collected at the Digestive Disease Research Center (DDRC) of Shariati Hospital, Tehran, Iran from January to October 2007. The 5'-UTR region of GBV-C RNA was detected using a novel in-house touchdown nested reverse transcription polymerase chain reaction (RT-PCR), the products were sequenced and the results were aligned and phylogenically analyzed. RESULTS: Of the 71 HCV-infected patients, 31 (43.6%) were found positive for GBV-C RNA. Sequencing and phylogenic analysis showed that the samples were Genotype 2 of GBV-C. CONCLUSIONS: It seems that there is a high rate of GBV-C infection among Iranian patients infected with chronic HCV. In comparison with the six reference genotypes, it was observed that all the samples were categorized in Genotype 2 of GBV-C, prevalent in North America, Africa and in European countries. PMID- 22312379 TI - A comparative study of non-invasive methods for fibrosis assessment in chronic HCV infection. AB - BACKGROUND AND AIMS: To compare several non-invasive methods of fibrosis assessment in chronic hepatitis C virus (HCV) infection (platelet count, the APRI score, the Forns score, the Lok score, FIB-4, Transient Elastography [TE]), versus percutaneous liver biopsy (LB). METHODS: Our study included 150 patients with chronic HCV infection in which LB, liver stiffness measurement (LSM) by means of TE and biological tests needed for calculating the scores (according to the classic formulas) were performed in the same session. RESULTS: The best test for predicting significant fibrosis (F = 2 Metavir) was LSM with AUROC-0.773, followed by APRI (AUROC-0.763), Forns (AUROC-0.744), platelet count (AUROC 0.732), Lok (AUROC-0.701) and FIB-4 (AUROC-0.669), but the differences were not statistically significant (P > 0.05). For excluding cirrhosis, all the tests had excellent NPV (>97%). The best test for predicting cirrhosis was LSM (AUROC 0.979), significantly better than platelet count (AUROC- 0.899, P = 0.022) and than FIB-4 (AUROC-0.839, P = 0.042), otherwise the differences were not statistically significant (P > 0.05). All of the non-invasive tests were statistically significantly correlated (P < 0.0001) to the severity of fibrosis: APRI r=0.570; Forns r=0.540; Lok r=0.4843; FIB-4 r=0.4171; platelet count r= 0.4842. CONCLUSIONS: LSM by means of TE seems to be more sensitive than APRI, Forns, Lok and FIB-4 scores and than platelet count for the prediction of significant fibrosis, but the differences are not statistically significant. The APRI score and Forns scores correctly identified most (71%) of the patients having, or not having, significant fibrosis. LSM was the best method for predicting cirrhosis, but all the evaluated tests had excellent predictive value (AUROCs 0.839-0.979). PMID- 22312380 TI - Evaluation of the effects of oral N-acetylcysteine and a placebo in paraclinical and oxidative stress parameters of patients with chronic hepatitis B. AB - BACKGROUND AND AIMS: The treatment of chronic hepatitis B (CHB) is a challenging problem today, and previous study has shown that oxidative stress causes the collective pathophysiological conditions of many hepatopathies, so other new therapeutic approaches are needed. Hence, in this study the paraclinical and oxidative stress parameters of the efficacy of N-acetyl cysteine (NAC) as an antioxidant in the treatment of CHB have been evaluated. METHODS: In this double blind placebo-controlled clinical trial study, 43 patients with CHB were enrolled in 2008 in Tehran, Iran. The patients were randomly assigned to receive either 1200 mg/day NAC or a placebo for 45 days. Paraclinical tests and oxidative stress parameters were measured on experimental day 0 and on day 45. RESULTS: Liver function tests, i.e. alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels were not significantly different in the NAC group and in the placebo group. A reduction in catalase (CAT) activity and an increase in glutathione concentration were statistically significant in the NAC group (P < 0.05). CONCLUSIONS: According to our results, oral NAC is not an effective adjuvant treatment for patients with CHB, but further research with a larger population is needed for the evaluation of the effectiveness of NAC in these patients. PMID- 22312381 TI - Seroprevalence study of hepatitis C and Hepatitis B virus among hospitalized intravenous drug users in Ahvaz, Iran (2002-2006). AB - BACKGROUND AND AIMS: Viral hepatitis is a serious complication among intravenous drug users (IDUs). The objectives of this study were to determine the seroprevalence of hepatitis B and C viruses (HBV and HCV), and associated risk factors among IDUs at a teaching hospital in Ahvaz, southwest Iran. METHODS: Medical records of 333 IDUs hospitalized from 2002 to 2006 at Razi Hospital, which is affiliated to Ahvaz Jundishapur University of Medical Sciences, were reviewed. Cases meeting the criteria for a diagnosis of viral hepatitis infection were included in this study. Patients' characteristics, clinical and laboratory findings were extracted. Data of cases with hepatitis virus infection (HVI), called the HVI group and without HVI, called the NHVI group, were compared, using the chi-square test for qualitative variables and the t-test for quantitative variables. Differences with a P < 0.05 were considered significant. RESULTS: Out of a total of 333 IDUs, 115 (34.5%), mostly male, with a mean age of 24.8+/-6.2 had HVI. More than 65% had a history of imprisonment. The mean duration of IDU was 4.5+/-1.6 years for the HVI group and 1.8+/-0.4 years for the NHVI group (P < 0.05). 85% of the HVI group and 45% of the NHVI group shared injection equipment (P < 0.05). 103 patients (30.9%) had HCV and 12 (3.6%) had HBV infection. There was a significant difference in age, duration of drug abuse, time spent in prison, sharing injection equipment, history of surgery, blood transfusion, packs of cigarettes per year and human immunodeficiency virus (HIV) co-infection between the two groups (P < 0.05). CONCLUSIONS: HVI in IDU population is a prevalent complication, and is associated with heavy smoking (high number of packs of cigarettes per year), sharing injection equipment, long duration of drug usage, long duration of prison stay, HIV co-infection, history of surgery, blood and blood products transfusion. Older age, longer duration of IDU and imprisonment put the cases at higher risk of acquiring HCV in comparison to HBV. PMID- 22312382 TI - Pulmonary complications in cirrhotic candidates for liver transplantation. AB - BACKGROUND AND AIMS: The determination of the prevalence of cardiopulmonary complications at a liver transplant center in Iran. METHODS: Ninety-nine patients (61 male and 38 female) with a mean age of 36.5 (15-66) years with proven cirrhosis were enrolled in this study. Patients with primary cardiac disease, current smokers, those with sepsis, hepatocellular carcinoma, recently ruptured esophageal varices and chronic pulmonary or renal diseases were excluded from the study. Sixty-nine patients had ascites. Forty-four patients had grade C Child Pugh classification. All patients were evaluated for respiratory function by chest X-ray (CXR), room air arterial blood gas, simultaneous pulse oximetry, cardiac echocardiography and spirometry. RESULTS: Sixty-one patients (66.1%) had a widened alveolar-arterial O2 difference ( > 20 mmHg); 14 (14.1%) had hypoxemia; 6 (6.1%) had mean pulmonary arterial pressure (MPAP) = 25-40 mmHg; 12 (12.1%) had tricuspid regurgitation; pleural effusion and lung restriction were detected in 4 (4%) and 50 (50.5%), respectively. P(A-a)O2 was negatively associated with pulmonary hypertension (P < 0.03) and tricuspid regurgitation (P < 0.005). Portal hypertension and portal vein thrombosis were detected in 91 and 8 patients, respectively. CONCLUSIONS: A widened alveolar-arterial oxygen difference was common in our patients, but hypoxemia occurred in 14% of patients. Portopulmonary hypertension was preponderant in those patients of male gender. PMID- 22312383 TI - A study of HDV in HBsAg positive patients in Tabriz, Northwestern Iran. AB - BACKGROUNDS AND AIMS: Hepatitis Delta Virus (HDV) is a defective ssRNA virus requiring the provision of hepatitis B virus (HBV) for packaging of new HDV virions. Since the epidemiological features of HDV in this part of Iran seem to be unknown, the aim of this research was to determine the seroprevalence of HDV of hepatitis B surface antigen positive (HBsAg+) in blood donors, injecting drug users, hemophiliacs, hemodialysis and thalassemic patients in the city of Tabriz in northwestern Iran. METHODS: The numbers of patients who were screened in the years 2006-2007 were 100 hemodialysis patients, 165 blood donors and 90 intravenous drug users, or a total of 355 patients who were HBsAg+ and randomly selected at the Tabriz Regional Educational Blood Center. Anti-HDV antibodies (IgM), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum samples were measured. RESULTS: Eight of the hemodialysis patients (8%), 3 of the 165 blood donors (1.8%) and 9 intravenous drug addicts (10%) were HDV IgM antibody-positive. Out of 152 serum samples collected in the hemophiliac population, only 11 samples were HBsAg+ (7.23%), and anti-HDV IgM antibodies were detected in just 2 cases. Also out of 112 thalassemic patients' sera specimens, only 2 samples was HBsAg+, and HDV-IgM antibodies were negative. The seropositivity of anti- HDV antibodies was 6.01%. The study of serum ALT levels in HBV-positive and HDV-positive patients showed obvious elevation in more than 95% of cases. CONCLUSIONS: The results show the endemicity of HDV infection in Tabriz. HDV infection in Iran could be controlled by nationwide HBV vaccination. PMID- 22312384 TI - Prevalence, sociodemographic characteristics and risk factors for hepatitis C infection among pregnant women in Calabar municipality, Nigeria. AB - BACKGROUND AND AIMS: The epidemiology and risk factors for hepatitis C virus (HCV) infection in developing countries where intravenous drug use (IDU) is uncommon its poorly understood. This study therefore aims to determine the prevalence of HCV and its associated risk factors among pregnant women in Calabar municipality. METHODS: A total of 506 out of 716 antenatal care (ANC) patients seen at the General Hospital, Mary Slessor Avenue, Calabar between August and November 2005 and the University of Calabar Teaching Hospital (UCTH) between October and November 2005 were evaluated for their HCV status using the One Step HCV Test kit (Binomial diagnostics, UK), with reference to the subjects' demographic and behavioural risk factors. RESULTS: HCV prevalence was determined to be 0.4% (2/506) and was only seen in women aged 38 years and over. Histories of blood transfusion, surgery, involvement in polygamous marriage, sharing of a toothbrush and female circumcision were all non-significant risk factors for the infecion. CONCLUSIONS: This study reveals a low HCV prevalence among pregnant women in Calabar municipality with no identifiable risk factor. The study calls for a re-evaluation of the transmission modes of HCV especially in developing countries where intravenous drug use is rare. PMID- 22312385 TI - The comparative efficacy and safety of peginterferon alpha-2a vs. 2b for the treatment of chronic HCV infection: a meta-analysis. AB - BACKGROUND AND AIMS: Two types of peginterferon, alpha-2a (PEG-IFN-alpha2a) and 2b (PEG-IFN-alpha2b), are approved for the treatment of hepatitis C infection. Several high-quality studies have compared the efficacy of these two types of interferon, but it seems that any of these trials had inadequate statistical power on their own to find even a tiny difference between these two medicines. We pooled the available data in the literature to find any small difference between these two medicines. METHODS: In a systematic review of the literature, randomized controlled trials comparing the use of PEG-alpha2a vs. 2b were assessed. The DerSimonian and Laird method was employed to run meta-analysis. The end points were virological responses. RESULTS: In 7 randomized controlled trials, 3518 patients were randomized to receive PEG-IFN-alpha2a + ribavirin (n=1762) or PEG-IFN-alpha2b + ribavirin (n=1756). Early virological response (EVR), early treatment response (ETR), and sustained virological response (SVR) were greater for patients treated with PEG-IFN-alpha2a. Odds Ratios (ORs) were 1.38 (95% confidence interval [CI] 1.11-1.71), 1.67 (95% CI 1.24-2.24), and 1.38 (95% CI 1.02-1.88) respectively. In the subset of naive patients with genotype 1/4 and 2, ORs of SVR were 1.38 (95% CI 1.02-1.88) and 4.06 (95% CI 1.67-9.86) respectively. PEG-IFN-alpha2a had significantly higher rate of neutropenia OR=1.50 (95% CI 1.25-1.79) but pooled OR for withdrawal rates was not significant [OR=0.78 (95% CI 0.47-1.29)]. CONCLUSIONS: PEG-IFN-alpha2a with similar safety is more effective than PEG-IFN-alpha2b. A longer duration of maximum serum concentration compared with PEG-IFN-alpha2b (168 vs. 48-72 h.) yields a greater SVR and higher neutropenia in PEG-IFN-alpha2a recipients. PMID- 22312386 TI - Interferon-alpha induced and ribavirin induced thyroid dysfunction in patients with chronic hepatitis C. AB - Chronic hepatitis C (CHC) is one of the commonest infectious diseases of the liver and may lead to cirrhosis or hepatocellular carcinoma. Combination therapy with pegylated interferon (PEG-IFN) and Ribavirin is the treatment of choice for CHC. Combination therapy is thought to act by means of antiviral mechanisms and immunomodulation. Thyroid dysfunction is the most common autoimmune adverse effect associated with combination therapy; hypothyroidism is more common than hyperthyroidism. Antithyroid antibodies and female sex have a predictive value in the development of interferon induced thyroid disease (IITD). Patients with CHC should be informed of the possibility of side effects on the thyroid gland. Screening for antithyroid antibodies and thyroid function tests should be performed in patients with CHC before the commencement of antiviral treatment, and during and after it. This article reviews different aspects of IITD, including its pathogenesis, clinical manifestations, association with treatment regimens and treatment response and the outcome of thyroid dysfunction. PMID- 22312387 TI - Multidrug-resistant hepatitis B virus strain in a chronic Turkish patient. AB - Hepatitis B virus (HBV) strains, resistant to at least two anti-HBV agents from different subclasses of nucleos(t)ide analogues (NUCs) without a cross-resistance profile, are defined as multidrug-resistant. However, there are limited in vivo data for resistance to multiple NUCs. In this study, we report the case of the emergence of a multidrug-resistant HBV strain in a Turkish patient receiving sequential therapy. Polymerase gene mutations of HBV were detected using direct sequencing, line probe assay and clonal analysis. Twelve months after the start of lamivudine (LAM) therapy, virological breakthrough occurred (4.2E+07 IU/ml) and the rtM204V variant was detected in the patient's sera: adefovir (ADV) was added to the therapy. ADV therapy was continued as monotherapy for 11 months, until the occurrence of clinical breakthrough i.e. alanine aminotransferase (ALT) 60 IU/L, and emergence of drug resistance to ADV (rtN236T). At that time, switch therapy was resumed with ADV + entecavir (ETV) in combination for 5 months. In the 18th month of the ETV monotherapy, direct sequencing showed reduced susceptibility to ETV (rtL180M+rtM204V). Currently, ETV + tenofovir (TDF) are being used as antiviral treatment and the HBV DNA load has decreased substantially (<1.0E+02 IU/ml). In conclusion, we have detected an HBV strain with multidrug-resistance, which had a very fast course of development. Patients with a multidrug-resistant profile should be more frequently followed up both by direct sequencing and line probe assay, for the detection of possible novel HBV variants and low level mutants present in the viral population, in case of the sudden emergence of drug resistance. PMID- 22312388 TI - HBV genotyping in HBsAg-positive blood donors from Southwestern Iran. PMID- 22312389 TI - MRI evaluation of liver iron concentration in patients with beta-thalassemia major. PMID- 22312390 TI - Hepatitis B Infection during Renal Replacement Therapy. PMID- 22312392 TI - Incidence of hepatocellular carcinoma in southeast iran. AB - BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a well-known consequence of chronic liver disease (CLD). The aim of this study was to extract the HCC incidence rate in the province of Kerman, located in southern part of Iran, and compare the data with other parts of the country. MATERIALS AND METHODS: All medical records related to HCC were collected through hospitals or outpatient services in public or private centers. The records of all oncology, radiotherapy, and pathology centers in Kerman province were actively searched between 1999 and 2006. The annual incidence of HCC around the country was calculated, using the national cancer registry database provided by the Health Ministry of IR Iran from 2005 to 2006. Using Stata version 8, the crude and age-sex-standardized annual incidence rates were computed. RESULTS: The crude annual incidence rates of HCC per 100,000 persons in Kerman and Iran were 0.522 (95% CI = 0.238- 0.88) and 0.199 (95% CI = 0.167-0.234), respectively. When adjusting for age and sex, the annual incidence rates of HCC in Kerman and Iran were 0.7 (95% CI = 0.4-1.1) and 0.2 (95% CI = 0.2-0.3) per 100,000 persons, respectively (P<0.01).The mean age of patients in Kerman was around 5.5 years younger than other parts of Iran (56.17 +/- 18.32 years versus 61.68 +/- 14.62 years; P=0.004). CONCLUSIONS: In general, the incidence of HCC is not very high in Iran; however, the higher incidence of HCC in Kerman and also the lower age of onset mandates further research to detect HCC's risk factors in this part of country. PMID- 22312391 TI - Hepatitis C virus as a multifaceted disease: a simple and updated approach for extrahepatic manifestations of hepatitis C virus infection. AB - Hepatitis C virus infection is an emerging disease and a public health problem in the world. There are accumulating data regarding extra hepatic manifestation of HCV, such as rheumatologic manifestations, endocrine, hematologic, dermatologic, renal, neurologic, and systemic manifestations. The therapy of them needs more attention to some exacerbations of extra hepatic manifestation and in some situation it needs different approaches. In this review we tried to provide latest evidence for extra hepatic manifestation and management of them. PMID- 22312393 TI - Associations among Genotype 1b Hepatitis C Virus Core Protein, Protein Kinase R, and Signal Transducer and Activator of Transcription 3. AB - BACKGROUND AND AIMS: Because hepatitis C virus (HCV) core protein (Core), protein kinase R (PKR), and signal transducer and activator of transcription 3 (STAT3) all play relevant roles in the pathogenesis of HCV, persistent infection and hepatocellular carcinoma (HCC) and PKR may interact with HCV Core. In this study, we further investigate the associations among HCV Core, PKR, and STAT3 and the mechanisms involved in these interactions. MATERIALS AND METHODS: Expression levels of HCV Core, PKR, eukaryotic initiation factor 2 (eIF-2alpha), phosphorylated eIF- 2alpha (p-eIF-2alpha), STAT3, and phosphorylated-STAT3 (p STAT3) were compared between Huh-7 and replicon cell-Huh-7 cells harboring the full length of genotype 1b HCV genomes. Co-immunoprecipitation and glutathione S transferase (GST) pull-down assay were conducted for HCV Core, PKR, and STAT3. RESULTS: HCV may have induced the expression of STAT3 and the activity of PKR (p eIF-2alpha). HCV Core, STAT3, and PKR appear to have interacted with one another. The N-terminal 1-126 amino acid (aa) of HCV Core contributed to an interaction between HCV Core and STAT3, and only full-length PKR bound to STAT3 and p-STAT3. CONCLUSIONS: These findings suggest that HCV Core, PKR, and STAT3 can interact with each other. Specifically, HCV Core may play its role through both PKR and STAT3. Alternatively, HCV Core's binding to and activation of STAT3 might be due to the interaction between HCV Core and PKR. The distinct interactions among these three molecules are important and may reveal a new molecular mechanism in the pathogenesis of HCV-persistent infection and HCV-related HCC. PMID- 22312394 TI - The relationship between lipid profile and severity of liver damage in cirrhotic patients. AB - BACKGROUND AND AIMS: An impaired lipid metabolism is often observed in patients with chronic liver diseases. To determine lipid profile in patients with cirrhosis and to asses if it relates to the severity of the cirrhosis. MATERIALS AND METHODS: In an analytical cross-sectional study, 50 patients with cirrhosis (case) and 50 age- and sex matched healthy normolipidemic patients (comparison) were studied. A questionnaire including personal characteristics,etiology of cirrhosis, pathologic criteria of CHILD and MELD and lipid profile (total, LDL, and HDL cholesterol and triglyceride) was completed for each patient. RESULTS: In patients with cirrhosis, there was a significant decrease in serum triglyceride, total, LDL and HDL cholesterol levels compared to the comparison group (mean of 82 vs 187, 138 vs 184, 80 vs 137, and 40 vs 44 mg/dL, respectively; all p<0.05). Comparison of lipid profile with pathologic progression of cirrhosis revealed that except for serum triglyceride level, serum lipid levels diminishe linearly with progression of liver damage. CONCLUSIONS: Serum total, LDL and HDL cholesterol level in patients with cirrhosis is inversely correlate with severity of cirrhosis. PMID- 22312395 TI - The effectiveness of nucleoside analogues in chronic hepatitis B patients unresponsive to interferon therapy: our clinical trials for one year. AB - BACKGROUND AND AIMS: We aimed to evaluate the effectiveness of nucleoside analogues such as Lamivudine, Adefovir,Entacavir, and Tenofovir in patients with chronic hepatitis B who failed to respond to interferon therapy and relapsed. MATERIALS AND METHODS: We followed a total of 73 patients with hepatitis B in the hepatitis outpatient clinic in our hospital. The patients subsequently received nucleoside analogues therapy and their treatment data were evaluated retrospectively. The biochemical and virological response rates were evaluated at 3 and 12 months, and we compared these results with the results of treatment naive patients. RESULTS: There were 29 (39.7%) HbeAg-positive and 44 (60.3%) HbeAg-negative patients, and their mean age was 35.8 (+/-13.4) years. Of these patients, 33, 18, 13 and 9 received Entacavir, Tenofovir, Lamivudine, and Adefovir treatment,respectively. In HbeAg-negative patients, at 3 months the biochemical and virological response (early response) rates were observed to be 91% and 98%), and at 12 months the two rates were 93% and 73%, respectively. In HbeAg-positive patients, the biochemical and virological response rates at 3 months were 83% and 97%, and the rates at 12 months were 90% and 48%, respectively. CONCLUSIONS: In CHB therapy with treatment-resistent patients, nucleoside analogues may be preferable. There are disadvantages to nucleoside analogues, such as a risk of developing resistance during therapy, reduced HBeAg seroconversion compared to interferons, and the therapy's ambiguous duration. In our study, in HbeAg-negative patients who received nucleoside analogues, a lower biochemical response rate was detected in patients with 1 year of Lamivudine therapy compared to other therapies. For HbeAg-positive patients, the virological response rate was higher in 1 year of Tenofovir therapy than with other therapies. PMID- 22312396 TI - Prevalence and clinical significance of hepatitis B Basal core promoter and precore gene mutations in southern Iranian patients. AB - BACKGROUND AND AIMS: To investigate the prevalence and pattern of PC and BCP mutations and their clinical significance in patients with genotype D chronic hepatitis B infection in the Fars province of southern Iran. MATERIALS AND METHODS: From January 2007 to March 2008, we evaluated 44 patients with chronic hepatitis B infection who were referred to our hepatology clinics affiliated with the Shiraz University of Medical Science. All Patients were HBeAg Negative and HBeAb positive. Basal core promoter and precore mutations in these patients were evaluated with clinical phenotype and laboratory tests. RESULTS: The mean age of the patients was 37.21 +/- 10.54 years. Twenty-seven patients (61.4%) had no mutations, whereas 17 patients (38.6%) had mutations in the precore or basal core promoter regions or both. The mean serum ALT level in mutation-free patients was 59.74 +/- 55.86 IUL, whereas patients with PC and BCP mutations had a mean serum ALT level of 71.35 +/- 59.49 IUL. The mean serum AST level in patients with mutations was higher than for patients without mutations (59.53 +/- 41.35 IUL vs. 40.65 +/- 25.21 IUL, respectively). There was no statistically significant difference between the mutation and mutation-free groups in terms of age, sex, and liver enzyme levels (P > 0.05). Fourteen of the 44 patients (31.8%) had mutations in the precore region (G 1896A). 17 patients (38.6%) had mutations in basal core promoter region. CONCLUSION: This study revealed a high prevalence of precore and basal core promoter mutations in southern Iran. Although no statistically significant difference was noted in liver enzymes, patients with mutations had higher liver enzymes in comparison with mutation-free patients. PMID- 22312397 TI - Induced HBs antigenemia in healthy adults after immunization with two different hepatitis B recombinant vaccines. AB - BACKGROUND AND AIMS: Currently, vaccination is the most effective protective tool against hepatitis B virus infection. Some studies have shown that positive results for a hepatitis B virus surface antigen (HBsAg) test may be seen after vaccination. MATERIALS AND METHODS: In this clinical trial study, 62 healthy adult volunteers were randomly assigned to receive either the Engerix-B or the Hepavax-Gene hepatitis B recombinant vaccine. Blood samples were drawn 1, 3, and 5 days after vaccination and were tested for HBsAg using two different ELISA kits (Behring and Mega). RESULTS: HBsAg was positive in 5, 3, and 2 participants of the Engerix-B group in the 1st, 3rd, and 5th days after vaccination, respectively, using the Behring ELISA kit the test was positive in only one subject in the Hepavax-Gene group, on the 5th day after vaccination. No positive result was seen in any groups when the Mega ELISA kit was used to test the specimens. CONCLUSIONS: Our results showed transient HBsAg antigenemia after vaccination against hepatitis B. This condition depends on the type of vaccine and the HBsAg diagnostic test. PMID- 22312398 TI - Genotype A2/adw2 Strain of Hepatitis B Virus in Turkey. AB - BACKGROUND AND AIMS: Previous studies have demonstrated the dominance of genotype D subtype ayw in patients with hepatitis B virus infection in Turkey. The aim of the present study is to report, for the first time, genotype A2 subtype adw2 of hepatitis B virus in a patient who is an inactive hepatitis B carrier in Turkey. MATERIALS AND METHODS: Hepatitis B virus DNA isolated from the serum sample was amplified by polymerase chain reaction. The polymerase gene segment of the hepatitis B virus was directly sequenced. A distance matrix/UPGMA comparison was used for phylogenetic analysis, and the genotype of the virus was identified accordingly. The subgenotype and subtype of hepatitis B virus were also detected. RESULTS: The genotyping of the patient revealed that the isolated hepatitis B virus was genotype A2/adw2. DISCUSSION: The subtype is inconsistent with the previous data from Turkey; specifically, the identification of the A2/adw2 subtype of the hepatitis B virus in an inactive carrier is the first such case in Turkey. This finding suggests that the transmission of another genotype besides genotype D subtype ayw of the hepatitis B virus is possible in Turkey. PMID- 22312399 TI - High hepatitis B virus load in a patient with severe polyarthritis nodosa. AB - One of the extra-hepatic manifestations of hepatitis B virus is polyarteritis nodosa (PAN). It may involve medium- and small-sized arteries in any organ. Concurrency of these two diseases may be life threatening and both should be treated. Herein, we report on a patient with severe PAN and high hepatitis B virus load. The patient was an 18-year-old boy with multiple progressive wounds in the skin, referred to our center. The preliminary evaluation showed vasculitis in the skin biopsy compatible with PAN. He was treated with low dose prednisolone and lamivudine for three years. However, his condition got worse and ulcers on his leg became life threatening. The viral load was 17,000,000 copy/mL. The wound developed superimposed resistant bacterial infection. The patient was then treated with two antiviral drugs-lamivudin 100 mg/day plus adefovir 10 mg/day-and high dose cyclophosphamide (750 mg, once a month) and prednisolone (60 mg/day for one month). After six months of treatment, viral load decreased to 100,000 copy/mL and wounds healed. We concluded that high viral load of hepatitis B virus may play an important role in the severity of PAN. We recommend combination therapy with two antiviral agents with high dose of immunosuppressive drugs until both the diseases resolve significantly. PMID- 22312400 TI - The Controversial Link between Hepatitis B Virus and Celiac Disease. PMID- 22312401 TI - Celiac disease and viral B hepatitis: lessons for clinical practice. PMID- 22312402 TI - Relationship between Hepatitis B Virus Infection and Celiac Disease. PMID- 22312403 TI - Celiac disease and liver. PMID- 22312404 TI - Hepatitis B and celiac disease. PMID- 22312405 TI - Persistence of diarrheal pathogens is associated with continued recruitment of plasmablasts in the circulation. AB - Intestinal antigen encounter leads to recirculation of antigen-specific plasmablasts via lymphatics and blood back to the intestine. Investigating these gut-originating cells in blood provides a less invasive tool for studying intestinal immune responses, with the limitation that the cells disappear from the circulation in two weeks. No data exist on situations where pathogens persist in the intestine. Patients with Salmonella, Yersinia, or Campylobacter gastroenteritis and volunteers receiving an oral typhoid vaccine were assayed for plasmablasts specific to each subject's own pathogen/antigen weekly until the response faded. In vaccinees, plasmablasts disappeared in two weeks. In gastroenteritis, the response faded 2-3 and 3-7 weeks after the last positive Salmonella or Yersinia stool culture. Even in symptomless patients, pathogens persisting in the intestine keep seeding plasmablasts into the circulation. Assaying these cells might offer a powerful tool for research into diseases in which persisting microbes have a potential pathogenetic significance. PMID- 22312406 TI - Combination immunotherapy with 4-1BBL and CTLA-4 blockade for the treatment of prostate cancer. AB - Immune regulation has been shown to be involved in the progressive growth of some murine tumours. Interruption of immune regulatory pathways via activation of 4 1BB or cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) blockade appears to be a promising strategy for cancer immunotherapy. In this study, we examined the effectiveness of 4-1BBL-expressing tumor cell vaccine in combination with CTLA-4 blockade on rejection of murine prostate cancer RM-1. We found that the combination of both a vaccine consisting of 4-1BBL-expressing RM-1 cells and CTLA 4 blockade resulted in regression of RM-1 tumors and a significant increase in survival of the tumour cell recipients, compared to that of either treatment alone. The combined vaccination resulted in higher CTL against RM-1 cells and increased secretion of IFN-gamma, TNF-alpha, and IL-2 in the mix-cultured supernatant. These results suggest that combining activation of 4-1BB and blockade of CTLA-4 may offer a new strategy for prostate cancer immunotherapy. PMID- 22312409 TI - Severe breastfeeding difficulties: Existential lostness as a mother-Women's lived experiences of initiating breastfeeding under severe difficulties. AB - A majority of women in Sweden initiate breastfeeding but almost a quarter stop or wean the infant in the first few weeks after birth because of difficulties. In order to develop care that facilitates initiation of breastfeeding and enables mothers to realize their expectations concerning breastfeeding, it is necessary to understand what having severe breastfeeding difficulties means for women who experience them. The aim of this study is to describe the lived experiences of initiating breastfeeding under severe difficulties. A reflective lifeworld research design was used. Eight women, seven primiparous and one multipara, were interviewed within 2 months of giving birth. The essential meaning of the phenomenon is described as "Existential lostness as a mother forcing oneself into a constant fight". This pattern is further explicated through its constituents; shattered expectations, a lost time for closeness, being of no use to the infant, being forced to expose oneself, and gaining strength through sharing. The results show that mothers with severe breastfeeding difficulties feel alone and exposed because of their suffering and are lost in motherhood. Thus, adequate care for mothers should enhance the forming of a caring relationship through sharing rather than exposing. PMID- 22312407 TI - Immunopathological roles of cytokines, chemokines, signaling molecules, and pattern-recognition receptors in systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is an autoimmune disease with unknown etiology affecting more than one million individuals each year. It is characterized by B- and T-cell hyperactivity and by defects in the clearance of apoptotic cells and immune complexes. Understanding the complex process involved and the interaction between various cytokines, chemokines, signaling molecules, and pattern recognition receptors (PRRs) in the immune pathways will provide valuable information on the development of novel therapeutic targets for treating SLE. In this paper, we review the immunopathological roles of novel cytokines, chemokines, signaling molecules, PRRs, and their interactions in immunoregulatory networks and suggest how their disturbances may implicate pathological conditions in SLE. PMID- 22312408 TI - Modulation of tumor tolerance in primary central nervous system malignancies. AB - Central nervous system tumors take advantage of the unique immunology of the CNS and develop exquisitely complex stromal networks that promote growth despite the presence of antigen-presenting cells and tumor-infiltrating lymphocytes. It is precisely this immunological paradox that is essential to the survival of the tumor. We review the evidence for functional CNS immune privilege and the impact it has on tumor tolerance. In this paper, we place an emphasis on the role of tumor-infiltrating myeloid cells in maintaining stromal and vascular quiescence, and we underscore the importance of indoleamine 2,3-dioxygenase activity as a myeloid-driven tumor tolerance mechanism. Much remains to be discovered regarding the tolerogenic mechanisms by which CNS tumors avoid immune clearance. Thus, it is an open question whether tumor tolerance in the brain is fundamentally different from that of peripheral sites of tumorigenesis or whether it simply stands as a particularly strong example of such tolerance. PMID- 22312410 TI - Dealing with daily emotions-supportive activities for the elderly in a municipal care setting. AB - There are diverse descriptions of supportive activities in nursing to be found in the literature. What they have in common is their association with good care outcomes, but they may differ depending on the context in which the care is given. In a Swedish municipal elderly care setting, registered nurses (RN) work in a consultative way and they describe a part of their tasks as comprising supportive activities without specifying what kind of supportive activities they mean. The aim of the study was to explore the main concern of the support given by RN to a group of patients in an elderly home care setting. The study was conducted using Grounded Theory. Data were collected using nonparticipant observations regarding the supportive activities of 12 RN at the home of 36 patients between the ages of 80 and 102. Most of the home visit lasted about 40 min but some lasted for 90 min. The central category was about dealing with daily emotions. This was done by encouraging the situation and reducing the patient's limitations, but situations also occurred in which there was a gap of support. Support was about capturing the emotions that the patient expressed for a particular moment, but there were also situations in which RN chose not to give support. To develop a holistic eldercare, more knowledge is needed about the factors causing the RN to choose not to provide support on some occasions. PMID- 22312411 TI - Abdominal tumor characterization and recognition using superior-order cooccurrence matrices, based on ultrasound images. AB - The noninvasive diagnosis of the malignant tumors is an important issue in research nowadays. Our purpose is to elaborate computerized, texture-based methods for performing computer-aided characterization and automatic diagnosis of these tumors, using only the information from ultrasound images. In this paper, we considered some of the most frequent abdominal malignant tumors: the hepatocellular carcinoma and the colonic tumors. We compared these structures with the benign tumors and with other visually similar diseases. Besides the textural features that proved in our previous research to be useful in the characterization and recognition of the malignant tumors, we improved our method by using the grey level cooccurrence matrix and the edge orientation cooccurrence matrix of superior order. As resulted from our experiments, the new textural features increased the malignant tumor classification performance, also revealing visual and physical properties of these structures that emphasized the complex, chaotic structure of the corresponding tissue. PMID- 22312412 TI - Weighted least-squares finite element method for cardiac blood flow simulation with echocardiographic data. AB - As both fluid flow measurement techniques and computer simulation methods continue to improve, there is a growing need for numerical simulation approaches that can assimilate experimental data into the simulation in a flexible and mathematically consistent manner. The problem of interest here is the simulation of blood flow in the left ventricle with the assimilation of experimental data provided by ultrasound imaging of microbubbles in the blood. The weighted least squares finite element method is used because it allows data to be assimilated in a very flexible manner so that accurate measurements are more closely matched with the numerical solution than less accurate data. This approach is applied to two different test problems: a flexible flap that is displaced by a jet of fluid and blood flow in the porcine left ventricle. By adjusting how closely the simulation matches the experimental data, one can observe potential inaccuracies in the model because the simulation without experimental data differs significantly from the simulation with the data. Additionally, the assimilation of experimental data can help the simulation capture certain small effects that are present in the experiment, but not modeled directly in the simulation. PMID- 22312413 TI - Emerging technologies in endoscopic imaging. AB - Endoscopic imaging is in part responsible for the recent drop in deaths from gastrointestinal cancers and also for detecting pre-cancerous and non-cancerous conditions and allowing them to be treated effectively, although techniques are far from perfect. Endoscopic imaging has evolved considerably from fiber optic systems 50 years ago to high resolution and high definition systems used at present. Moreover, image enhancement using filters and processors has led to the technique of 'electronic chromoendoscopy' to visualize mucosal blood vessels and surface pit patterns clearly. Magnification by optical zoom or confocal laser microscopy has enabled real time diagnosis and 'virtual histology'. These techniques have contributed to the early detection, assessment and treatment of various gastrointestinal pathologies. The focus of future research is directed towards molecular targeted imaging. PMID- 22312414 TI - Reduced vancomycin susceptibility among clinical Staphylococcus aureus isolates ('the MIC Creep'): implications for therapy. AB - Methicillin-resistant S. aureus (MRSA) has emerged as the most common hospital acquired pathogen and is associated with increased morbidity and mortality compared with other strains. Vancomycin has been the cornerstone of treatment of patients with serious MRSA infections for some decades and while more than 99% of clinical S. aureus isolates remain susceptible to vancomycin, we are beginning to see strains of MRSA with reduced susceptibility. This review discusses this phenomenon, the predictors of infection with such forms of MRSA, and current and future management options. PMID- 22312415 TI - microRNA induced transdifferentiation. AB - Recent months have seen rapid advances in the field of transdifferentiation, specifically in the conversion of fibroblasts to neurons. Most surprising is the observation that the ability to drive these transitions is not limited to transcription factors, but that they can be promoted by microRNAs as well. Indeed, in one case, microRNAs alone induced the transdifferentiation of fibroblasts to neuron-like cells, albeit at a low efficiency. Here, we review this rapidly advancing field, discuss possible mechanisms underlying microRNA induced transdifferentiation and the potential for microRNAs to drive such transitions to any cell type of interest in vitro and in vivo. PMID- 22312416 TI - Lipids as conductors in the orchestra of life. AB - The lipid phosphatidic acid is an important metabolic intermediate in the biosynthesis of lipids in all eukaryotic cells, but it is even more than that. Phosphatidic acid is emerging as a lipid that is both composer and conductor, where in addition to its role as biosynthetic precursor (composer) it is also a potent signaling molecule (conductor) that integrates membrane biogenesis with nutrient sensing and cell growth. This article discusses recent advances in yeast that give praise for phosphatidic acid as one of life's conductors. PMID- 22312417 TI - Evidence Based Development of a Novel Lateral Fibula Plate (VariAx Fibula) Using a Real CT Bone Data Based Optimization Process During Device Development. AB - Development of novel implants in orthopaedic trauma surgery is based on limited datasets of cadaver trials or artificial bone models. A method has been developed whereby implants can be constructed in an evidence based method founded on a large anatomic database consisting of more than 2.000 datasets of bones extracted from CT scans. The aim of this study was the development and clinical application of an anatomically pre-contoured plate for the treatment of distal fibular fractures based on the anatomical database.48 Caucasian and Asian bone models (left and right) from the database were used for the preliminary optimization process and validation of the fibula plate. The implant was constructed to fit bilaterally in a lateral position of the fibula. Then a biomechanical comparison of the designed implant to the current gold standard in the treatment of distal fibular fractures (locking 1/3 tubular plate) was conducted. Finally, a clinical surveillance study to evaluate the grade of implant fit achieved was performed. The results showed that with a virtual anatomic database it was possible to design a fibula plate with an optimized fit for a large proportion of the population. Biomechanical testing showed the novel fibula plate to be superior to 1/3 tubular plates in 4-point bending tests. The clinical application showed a very high degree of primary implant fit. Only in a small minority of cases further intra-operative implant bending was necessary. Therefore, the goal to develop an implant for the treatment of distal fibular fractures based on the evidence of a large anatomical database could be attained. Biomechanical testing showed good results regarding the stability and the clinical application confirmed the high grade of anatomical fit. PMID- 22312418 TI - Combining graph and machine learning methods to analyze differences in functional connectivity across sex. AB - In this work we combine machine learning methods and graph theoretical analysis to investigate gender associated differences in resting state brain network connectivity. The set of all correlations computed from the fMRI resting state data is used as input features for classification. Two ensemble learning methods are used to perform the detection of the set of discriminative edges between groups (males vs. females) of brain networks: 1) Random Forest and 2) an ensemble method based on least angle shrinkage and selection operator (lasso) regressors. Permutation testing is used not only to assess significance of classification accuracy but also to evaluate significance of feature selection. Finally, these methods are applied to data downloaded from the Connectome Project website. Our results suggest that gender differences in brain function may be related to sexually dimorphic regional connectivity between specific critical nodes via gender-discriminative edges. PMID- 22312419 TI - Two-item sentence comprehension by a dog (Canis familiaris). AB - Syntax use by non-human animals remains a controversial issue. We present here evidence that a dog may respond to verbal requests composed of two independent terms, one referring to an object and the other to an action to be performed relative to the object. A female mongrel dog, Sofia, was initially trained to respond to action (point and fetch) and object (ball, key, stick, bottle and bear) terms which were then presented as simultaneous, combinatorial requests (e.g. ball fetch, stick point). Sofia successfully responded to object-action requests presented as single sentences, and was able to flexibly generalize her performance across different contexts. These results provide empirical evidence that dogs are able to extract the information contained in complex messages and to integrate it in directed performance, an ability which is shared with other linguistically trained animals and may represent a forerunner of syntactic functioning. PMID- 22312420 TI - Sleep disorders and demand for medical services: evidence from a population-based longitudinal study. AB - BACKGROUND: The aim of this study was to investigate whether insomnia and obstructive sleep apnea (OSA) were predictors of hospitalizations or emergency department visits during two years following the Sao Paulo Epidemiologic Sleep Study (EPISONO) sample. METHODS AND FINDINGS: All participants (n = 1,101) who underwent a baseline evaluation between July and December 2007 were contacted in December 2009 and asked to fill out a questionnaire about body weight changes, number of hospitalizations and visits to the emergency department. Participants lost during the follow-up period represented 3.2% (n = 35) and 7 subjects had died. Hospitalizations were reported by 116 volunteers (10.5%) and emergency department visits were reported by 136 participants (12.4%). The average body mass index (BMI) did not vary significantly between the first and the second assessment [26.7(95%CI:26.3-27.1) vs. 26.9(26.5-27.4) kg/m2]. After adjusting for confounders, a multiple logistic regression model revealed that female gender [1.4(1.0-1.9)], age >= 40 years, insomnia diagnosed according to the DSM-IV criteria [1.6(1.0-2.6)], and apnea-hypopnea index >= 15 [1.5(1.0-2.2)] were predictors of hospitalizations and/or demand for emergency services. CONCLUSION: Our study of a probabilistic sample of the Sao Paulo inhabitants shows that over a period of two years, insomnia and OSA were both associated with health impairment. Considering the high prevalence and public health burden of sleep disorders, the consequences of untreated disease for both the individual and society are undeniable and should be addressed. PMID- 22312421 TI - Potent phototoxicity of marine bunker oil to translucent herring embryos after prolonged weathering. AB - Pacific herring embryos (Clupea pallasi) spawned three months following the Cosco Busan bunker oil spill in San Francisco Bay showed high rates of late embryonic mortality in the intertidal zone at oiled sites. Dead embryos developed to the hatching stage (e.g. fully pigmented eyes) before suffering extensive tissue deterioration. In contrast, embryos incubated subtidally at oiled sites showed evidence of sublethal oil exposure (petroleum-induced cardiac toxicity) with very low rates of mortality. These field findings suggested an enhancement of oil toxicity through an interaction between oil and another environmental stressor in the intertidal zone, such as higher levels of sunlight-derived ultraviolet (UV) radiation. We tested this hypothesis by exposing herring embryos to both trace levels of weathered Cosco Busan bunker oil and sunlight, with and without protection from UV radiation. Cosco Busan oil and UV co-exposure were both necessary and sufficient to induce an acutely lethal necrotic syndrome in hatching stage embryos that closely mimicked the condition of dead embryos sampled from oiled sites. Tissue levels of known phototoxic polycyclic aromatic compounds were too low to explain the observed degree of phototoxicity, indicating the presence of other unidentified or unmeasured phototoxic compounds derived from bunker oil. These findings provide a parsimonious explanation for the unexpectedly high losses of intertidal herring spawn following the Cosco Busan spill. The chemical composition and associated toxicity of bunker oils should be more thoroughly evaluated to better understand and anticipate the ecological impacts of vessel-derived spills associated with an expanding global transportation network. PMID- 22312422 TI - From food to offspring down: tissue-specific discrimination and turn-over of stable isotopes in herbivorous waterbirds and other avian foraging guilds. AB - Isotopic discrimination and turn-over are fundamental to the application of stable isotope ecology in animals. However, detailed information for specific tissues and species are widely lacking, notably for herbivorous species. We provide details on tissue-specific carbon and nitrogen discrimination and turn over times from food to blood, feathers, claws, egg tissues and offspring down feathers in four species of herbivorous waterbirds. Source-to-tissue discrimination factors for carbon (delta13C) and nitrogen stable isotope ratios (delta15N) showed little variation across species but varied between tissues. Apparent discrimination factors ranged between -0.5 to 2.50/00 for delta13C and 2.8 to 5.20/00 for delta15N, and were more similar between blood components than between keratinous tissues or egg tissue. Comparing these results with published data from other species we found no effect of foraging guild on discrimination factors for carbon but a significant foraging-guild effect for nitrogen discrimination factors.Turn-over of delta13C in tissues was most rapid in blood plasma, with a half-life of 4.3 d, whereas delta13C in blood cells had a half life of approximately 32 d. Turn-over times for albumen and yolk in laying females were similar to those of blood plasma, at 3.2 and 6.0 d respectively. Within yolk, we found decreasing half-life times of delta13C from inner yolk (13.3 d) to outer yolk (3.1 d), related to the temporal pattern of tissue formation.We found similarities in tissue-specific turn-over times across all avian species studied to date. Yet, while generalities regarding discrimination factors and tissue turn-over times can be made, a large amount of variation remains unexplained. PMID- 22312423 TI - Socioeconomic status (SES) and children's intelligence (IQ): in a UK representative sample SES moderates the environmental, not genetic, effect on IQ. AB - BACKGROUND: The environment can moderate the effect of genes - a phenomenon called gene-environment (GxE) interaction. Several studies have found that socioeconomic status (SES) modifies the heritability of children's intelligence. Among low-SES families, genetic factors have been reported to explain less of the variance in intelligence; the reverse is found for high-SES families. The evidence however is inconsistent. Other studies have reported an effect in the opposite direction (higher heritability in lower SES), or no moderation of the genetic effect on intelligence. METHODS: Using 8716 twin pairs from the Twins Early Development Study (TEDS), we attempted to replicate the reported moderating effect of SES on children's intelligence at ages 2, 3, 4, 7, 9, 10, 12 and 14: i.e., lower heritability in lower-SES families. We used a twin model that allowed for a main effect of SES on intelligence, as well as a moderating effect of SES on the genetic and environmental components of intelligence. RESULTS: We found greater variance in intelligence in low-SES families, but minimal evidence of GxE interaction across the eight ages. A power calculation indicated that a sample size of about 5000 twin pairs is required to detect moderation of the genetic component of intelligence as small as 0.25, with about 80% power - a difference of 11% to 53% in heritability, in low- (-2 standard deviations, SD) and high-SES (+2 SD) families. With samples at each age of about this size, the present study found no moderation of the genetic effect on intelligence. However, we found the greater variance in low-SES families is due to moderation of the environmental effect - an environment-environment interaction. CONCLUSIONS: In a UK representative sample, the genetic effect on intelligence is similar in low- and high-SES families. Children's shared experiences appear to explain the greater variation in intelligence in lower SES. PMID- 22312424 TI - Viremic HIV infected individuals with high CD4 T cells and functional envelope proteins show anti-gp41 antibodies with unique specificity and function. AB - BACKGROUND: CD4 T-cell decay is variable among HIV-infected individuals. In exceptional cases, CD4 T-cell counts remain stable despite high plasma viremia. HIV envelope glycoprotein (Env) properties, namely tropism, fusion or the ability to induce the NK ligand NKp44L, or host factors that modulate Env cytopathic mechanisms may be modified in such situation. METHODS: We identified untreated HIV-infected individuals showing non-cytopathic replication (VL>10,000 copies/mL and CD4 T-cell decay<50 cells/uL/year, Viremic Non Progressors, VNP) or rapid progression (CD4 T-cells<350 cells/uL within three years post-infection, RP). We isolated full-length Env clones and analyzed their functions (tropism, fusion activity and capacity to induce NKp44L expression on CD4 cells). Anti-Env humoral responses were also analyzed. RESULTS: Env clones isolated from VNP or RP individuals showed no major phenotypic differences. The percentage of functional clones was similar in both groups. All clones tested were CCR5-tropic and showed comparable expression and fusogenic activity. Moreover, no differences were observed in their capacity to induce NKp44L expression on CD4 T cells from healthy donors through the 3S epitope of gp41. In contrast, anti- Env antibodies showed clear functional differences: plasma from VNPs had significantly higher capacity than RPs to block NKp44L induction by autologous viruses. Consistently, CD4 T-cells isolated from VNPs showed undetectable NKp44L expression and specific antibodies against a variable region flanking the highly conserved 3S epitope were identified in plasma samples from these patients. Conversely, despite continuous antigen stimulation, VNPs were unable to mount a broad neutralizing response against HIV. CONCLUSIONS: Env functions (fusion and induction of NKp44L) were similar in viremic patients with slow or rapid progression to AIDS. However, differences in humoral responses against gp41 epitopes nearby 3S sequence may contribute to the lack of CD4 T cell decay in VNPs by blocking the induction of NKp44L by gp41. PMID- 22312425 TI - Predicting target DNA sequences of DNA-binding proteins based on unbound structures. AB - DNA-binding proteins such as transcription factors use DNA-binding domains (DBDs) to bind to specific sequences in the genome to initiate many important biological functions. Accurate prediction of such target sequences, often represented by position weight matrices (PWMs), is an important step to understand many biological processes. Recent studies have shown that knowledge-based potential functions can be applied on protein-DNA co-crystallized structures to generate PWMs that are considerably consistent with experimental data. However, this success has not been extended to DNA-binding proteins lacking co-crystallized structures. This study aims at investigating the possibility of predicting the DNA sequences bound by DNA-binding proteins from the proteins' unbound structures (structures of the unbound state). Given an unbound query protein and a template complex, the proposed method first employs structure alignment to generate synthetic protein-DNA complexes for the query protein. Once a complex is available, an atomic-level knowledge-based potential function is employed to predict PWMs characterizing the sequences to which the query protein can bind. The evaluation of the proposed method is based on seven DNA-binding proteins, which have structures of both DNA-bound and unbound forms for prediction as well as annotated PWMs for validation. Since this work is the first attempt to predict target sequences of DNA-binding proteins from their unbound structures, three types of structural variations that presumably influence the prediction accuracy were examined and discussed. Based on the analyses conducted in this study, the conformational change of proteins upon binding DNA was shown to be the key factor. This study sheds light on the challenge of predicting the target DNA sequences of a protein lacking co-crystallized structures, which encourages more efforts on the structure alignment-based approaches in addition to docking- and homology modeling-based approaches for generating synthetic complexes. PMID- 22312426 TI - Implications of extreme life span in clonal organisms: millenary clones in meadows of the threatened seagrass Posidonia oceanica. AB - The maximum size and age that clonal organisms can reach remains poorly known, although we do know that the largest natural clones can extend over hundreds or thousands of metres and potentially live for centuries. We made a review of findings to date, which reveal that the maximum clone age and size estimates reported in the literature are typically limited by the scale of sampling, and may grossly underestimate the maximum age and size of clonal organisms. A case study presented here shows the occurrence of clones of slow-growing marine angiosperm Posidonia oceanica at spatial scales ranging from metres to hundreds of kilometres, using microsatellites on 1544 sampling units from a total of 40 locations across the Mediterranean Sea. This analysis revealed the presence, with a prevalence of 3.5 to 8.9%, of very large clones spreading over one to several (up to 15) kilometres at the different locations. Using estimates from field studies and models of the clonal growth of P. oceanica, we estimated these large clones to be hundreds to thousands of years old, suggesting the evolution of general purpose genotypes with large phenotypic plasticity in this species. These results, obtained combining genetics, demography and model-based calculations, question present knowledge and understanding of the spreading capacity and life span of plant clones. These findings call for further research on these life history traits associated with clonality, considering their possible ecological and evolutionary implications. PMID- 22312427 TI - Season of sampling and season of birth influence serotonin metabolite levels in human cerebrospinal fluid. AB - BACKGROUND: Animal studies have revealed seasonal patterns in cerebrospinal fluid (CSF) monoamine (MA) turnover. In humans, no study had systematically assessed seasonal patterns in CSF MA turnover in a large set of healthy adults. METHODOLOGY/PRINCIPAL FINDINGS: Standardized amounts of CSF were prospectively collected from 223 healthy individuals undergoing spinal anesthesia for minor surgical procedures. The metabolites of serotonin (5-hydroxyindoleacetic acid, 5 HIAA), dopamine (homovanillic acid, HVA) and norepinephrine (3-methoxy-4 hydroxyphenylglycol, MPHG) were measured using high performance liquid chromatography (HPLC). Concentration measurements by sampling and birth dates were modeled using a non-linear quantile cosine function and locally weighted scatterplot smoothing (LOESS, span = 0.75). The cosine model showed a unimodal season of sampling 5-HIAA zenith in April and a nadir in October (p-value of the amplitude of the cosine = 0.00050), with predicted maximum (PC(max)) and minimum (PC(min)) concentrations of 173 and 108 nmol/L, respectively, implying a 60% increase from trough to peak. Season of birth showed a unimodal 5-HIAA zenith in May and a nadir in November (p = 0.00339; PC(max) = 172 and PC(min) = 126). The non-parametric LOESS showed a similar pattern to the cosine in both season of sampling and season of birth models, validating the cosine model. A final model including both sampling and birth months demonstrated that both sampling and birth seasons were independent predictors of 5-HIAA concentrations. CONCLUSION: In subjects without mental illness, 5-HT turnover shows circannual variation by season of sampling as well as season of birth, with peaks in spring and troughs in fall. PMID- 22312429 TI - NGS QC Toolkit: a toolkit for quality control of next generation sequencing data. AB - Next generation sequencing (NGS) technologies provide a high-throughput means to generate large amount of sequence data. However, quality control (QC) of sequence data generated from these technologies is extremely important for meaningful downstream analysis. Further, highly efficient and fast processing tools are required to handle the large volume of datasets. Here, we have developed an application, NGS QC Toolkit, for quality check and filtering of high-quality data. This toolkit is a standalone and open source application freely available at http://www.nipgr.res.in/ngsqctoolkit.html. All the tools in the application have been implemented in Perl programming language. The toolkit is comprised of user-friendly tools for QC of sequencing data generated using Roche 454 and Illumina platforms, and additional tools to aid QC (sequence format converter and trimming tools) and analysis (statistics tools). A variety of options have been provided to facilitate the QC at user-defined parameters. The toolkit is expected to be very useful for the QC of NGS data to facilitate better downstream analysis. PMID- 22312428 TI - Environmentally realistic exposure to the herbicide atrazine alters some sexually selected traits in male guppies. AB - Male mating signals, including ornaments and courtship displays, and other sexually selected traits, like male-male aggression, are largely controlled by sex hormones. Environmental pollutants, notably endocrine disrupting compounds, can interfere with the proper functioning of hormones, thereby impacting the expression of hormonally regulated traits. Atrazine, one of the most widely used herbicides, can alter sex hormone levels in exposed animals. I tested the effects of environmentally relevant atrazine exposures on mating signals and behaviors in male guppies, a sexually dimorphic freshwater fish. Prolonged atrazine exposure reduced the expression of two honest signals: the area of orange spots (ornaments) and the number of courtship displays performed. Atrazine exposure also reduced aggression towards competing males in the context of mate competition. In the wild, exposure levels vary among individuals because of differential distribution of the pollutants across habitats; hence, differently impacted males often compete for the same mates. Disrupted mating signals can reduce reproductive success as females avoid mating with perceptibly suboptimal males. Less aggressive males are at a competitive disadvantage and lose access to females. This study highlights the effects of atrazine on ecologically relevant mating signals and behaviors in exposed wildlife. Altered reproductive traits have important implications for population dynamics, evolutionary patterns, and conservation of wildlife species. PMID- 22312430 TI - Helicobacter pylori CagA triggers expression of the bactericidal lectin REG3gamma via gastric STAT3 activation. AB - BACKGROUND: Most of what is known about the Helicobacter pylori (H. pylori) cytotoxin, CagA, pertains to a much-vaunted role as a determinant of gastric inflammation and cancer. Little attention has been devoted to potential roles of CagA in the majority of H. pylori infected individuals not showing oncogenic progression, particularly in relation to host tolerance. Regenerating islet derived (REG)3gamma encodes a secreted C-type lectin that exerts direct bactericidal activity against Gram-positive bacteria in the intestine. Here, we extend this paradigm of lectin-mediated innate immunity, showing that REG3gamma expression is triggered by CagA in the H. pylori-infected stomach. METHODOLOGY/PRINCIPAL FINDINGS: In human gastric mucosal tissues, REG3gamma expression was significantly increased in CagA-positive, compared to CagA negative H. pylori infected individuals. Using transfected CagA-inducible gastric MKN28 cells, we recapitulated REG3gamma induction in vitro, also showing that tyrosine phosphorylated, not unphosphorylated CagA triggers REG3gamma transcription. In concert with induced REG3gamma, pro-inflammatory signalling downstream of the gp130 cytokine co-receptor via the signal transducer and activator of transcription (STAT)3 and transcription of two cognate ligands, interleukin(IL)-11 and IL-6, were significantly increased. Exogenous IL-11, but not IL-6, directly stimulated STAT3 activation and REG3gamma transcription. STAT3 siRNA knockdown or IL-11 receptor blockade respectively abrogated or subdued CagA dependent REG3gamma mRNA induction, thus demonstrating a requirement for uncompromised signalling via the IL-11/STAT3 pathway. Inhibition of the gp130 related SHP2-(Ras)-ERK pathway did not affect CagA-dependent REG3gamma induction, but strengthened STAT3 activation as well as augmenting transcription of mucosal innate immune regulators, IL-6, IL-8 and interferon-response factor (IRF)1. CONCLUSIONS/SIGNIFICANCE: Our results support a model of CagA-directed REG3gamma expression in gastric epithelial cells via activation of the IL-11/gp130/STAT3 pathway. This response might allow Gram-negative H. pylori to manipulate host immunity to favour its own survival, by reducing the fitness of co-habiting Gram positive bacteria with which it competes for resources in the gastric mucosal niche. PMID- 22312431 TI - Coronavirus papain-like proteases negatively regulate antiviral innate immune response through disruption of STING-mediated signaling. AB - Viruses have evolved elaborate mechanisms to evade or inactivate the complex system of sensors and signaling molecules that make up the host innate immune response. Here we show that human coronavirus (HCoV) NL63 and severe acute respiratory syndrome (SARS) CoV papain-like proteases (PLP) antagonize innate immune signaling mediated by STING (stimulator of interferon genes, also known as MITA/ERIS/MYPS). STING resides in the endoplasmic reticulum and upon activation, forms dimers which assemble with MAVS, TBK-1 and IKKepsilon, leading to IRF-3 activation and subsequent induction of interferon (IFN). We found that expression of the membrane anchored PLP domain from human HCoV-NL63 (PLP2-TM) or SARS-CoV (PLpro-TM) inhibits STING-mediated activation of IRF-3 nuclear translocation and induction of IRF-3 dependent promoters. Both catalytically active and inactive forms of CoV PLPs co-immunoprecipitated with STING, and viral replicase proteins co-localize with STING in HCoV-NL63-infected cells. Ectopic expression of catalytically active PLP2-TM blocks STING dimer formation and negatively regulates assembly of STING-MAVS-TBK1/IKKepsilon complexes required for activation of IRF-3. STING dimerization was also substantially reduced in cells infected with SARS-CoV. Furthermore, the level of ubiquitinated forms of STING, RIG-I, TBK1 and IRF-3 are reduced in cells expressing wild type or catalytic mutants of PLP2-TM, likely contributing to disruption of signaling required for IFN induction. These results describe a new mechanism used by CoVs in which CoV PLPs negatively regulate antiviral defenses by disrupting the STING-mediated IFN induction. PMID- 22312432 TI - Polyglutamine repeats are associated to specific sequence biases that are conserved among eukaryotes. AB - Nine human neurodegenerative diseases, including Huntington's disease and several spinocerebellar ataxia, are associated to the aggregation of proteins comprising an extended tract of consecutive glutamine residues (polyQs) once it exceeds a certain length threshold. This event is believed to be the consequence of the expansion of polyCAG codons during the replication process. This is in apparent contradiction with the fact that many polyQs-containing proteins remain soluble and are encoded by invariant genes in a number of eukaryotes. The latter suggests that polyQs expansion and/or aggregation might be counter-selected through a genetic and/or protein context. To identify this context, we designed a software that scrutinize entire proteomes in search for imperfect polyQs. The nature of residues flanking the polyQs and that of residues other than Gln within polyQs (insertions) were assessed. We discovered strong amino acid residue biases robustly associated to polyQs in the 15 eukaryotic proteomes we examined, with an over-representation of Pro, Leu and His and an under-representation of Asp, Cys and Gly amino acid residues. These biases are conserved amongst unrelated proteins and are independent of specific functional classes. Our findings suggest that specific residues have been co-selected with polyQs during evolution. We discuss the possible selective pressures responsible of the observed biases. PMID- 22312433 TI - Regrowing the adult brain: NF-kappaB controls functional circuit formation and tissue homeostasis in the dentate gyrus. AB - Cognitive decline during aging is correlated with a continuous loss of cells within the brain and especially within the hippocampus, which could be regenerated by adult neurogenesis. Here we show that genetic ablation of NF kappaB resulted in severe defects in the neurogenic region (dentate gyrus) of the hippocampus. Despite increased stem cell proliferation, axogenesis, synaptogenesis and neuroprotection were hampered, leading to disruption of the mossy fiber pathway and to atrophy of the dentate gyrus during aging. Here, NF kappaB controls the transcription of FOXO1 and PKA, regulating axogenesis. Structural defects culminated in behavioral impairments in pattern separation. Re activation of NF-kappaB resulted in integration of newborn neurons, finally to regeneration of the dentate gyrus, accompanied by a complete recovery of structural and behavioral defects. These data identify NF-kappaB as a crucial regulator of dentate gyrus tissue homeostasis suggesting NF-kappaB to be a therapeutic target for treating cognitive and mood disorders. PMID- 22312434 TI - Murine GRPR and stathmin control in opposite directions both cued fear extinction and neural activities of the amygdala and prefrontal cortex. AB - Extinction is an integral part of normal healthy fear responses, while it is compromised in several fear-related mental conditions in humans, such as post traumatic stress disorder (PTSD). Although much research has recently been focused on fear extinction, its molecular and cellular underpinnings are still unclear. The development of animal models for extinction will greatly enhance our approaches to studying its neural circuits and the mechanisms involved. Here, we describe two gene-knockout mouse lines, one with impaired and another with enhanced extinction of learned fear. These mutant mice are based on fear memory related genes, stathmin and gastrin-releasing peptide receptor (GRPR). Remarkably, both mutant lines showed changes in fear extinction to the cue but not to the context. We performed indirect imaging of neuronal activity on the second day of cued extinction, using immediate-early gene c-Fos. GRPR knockout mice extinguished slower (impaired extinction) than wildtype mice, which was accompanied by an increase in c-Fos activity in the basolateral amygdala and a decrease in the prefrontal cortex. By contrast, stathmin knockout mice extinguished faster (enhanced extinction) and showed a decrease in c-Fos activity in the basolateral amygdala and an increase in the prefrontal cortex. At the same time, c-Fos activity in the dentate gyrus was increased in both mutant lines. These experiments provide genetic evidence that the balance between neuronal activities of the amygdala and prefrontal cortex defines an impairment or facilitation of extinction to the cue while the hippocampus is involved in the context-specificity of extinction. PMID- 22312435 TI - Responsiveness to 6-n-propylthiouracil (PROP) is associated with salivary levels of two specific basic proline-rich proteins in humans. AB - Thiourea tasting can be predictive of individual differences in bitter taste responses, general food preferences and eating behavior, and could be correlated with saliva chemical composition. We investigated the possible relationship between PROP bitter taste responsiveness and the salivary proteome in subjects genotyped for TAS2R38 and gustin gene polymorphisms. Taste perception intensity evoked by PROP and NaCl solutions was measured in sixty-three volunteers (21 males, 42 females, age 25+/-3 y) to establish their PROP taster status, and 24 PROP super-tasters and 21 nontasters were selected to participate in the study. TAS2R38 and gustin gene molecular analysis were performed using PCR techniques. Qualitative and quantitative determination of salivary proteins was performed by HPLC-ESI-MS before and after PROP taste stimulation. PROP super-tastings was strongly associated with the 'taster' variant (PAV haplotype) of TAS2R38 and the A allele of rs2274333 polymorphism in the gustin gene and nontasting was associated with the minor alleles at both loci. ANOVA revealed that basal levels of II-2 and Ps-1 proteins, belonging to the basic proline-rich protein (bPRPs) family, were significantly higher in PROP super-taster than in nontaster un stimulated saliva, and that PROP stimulation elicited a rapid increase in the levels of these same proteins only in PROP super-taster saliva. These data show for the first time that responsiveness to PROP is associated with salivary levels of II-2 peptide and Ps-1 protein, which are products of the PRB1 gene. These findings suggest that PRB1, in addition to TAS2R38 and gustin, could contribute to individual differences in thiourea sensitivity, and the expression of the PROP phenotype as a complex genetic trait. PMID- 22312436 TI - Measuring the impacts of community-based grasslands management in Mongolia's Gobi. AB - We assessed a donor-funded grassland management project designed to create both conservation and livelihood benefits in the rangelands of Mongolia's Gobi desert. The project ran from 1995 to 2006, and we used remote sensing Normalized Differential Vegetation Index data from 1982 to 2009 to compare project grazing sites to matched control sites before and after the project's implementation. We found that the productivity of project grazing sites was on average within 1% of control sites for the 20 years before the project but generated 11% more biomass on average than the control areas from 2000 to 2009. To better understand the benefits of the improved grasslands to local people, we conducted 280 household interviews, 8 focus group discussions, and 31 key informant interviews across 6 districts. We found a 12% greater median annual income as well as a range of other socioeconomic benefits for project households compared to control households in the same areas. Overall, the project generated measurable benefits to both nature and people. The key factors underlying project achievements that may be replicable by other conservation projects include the community-driven approach of the project, knowledge exchanges within and between communities inside and outside the country, a project-supported local community organizer in each district, and strong community leadership. PMID- 22312437 TI - Conditional ablation of Ezh2 in murine hearts reveals its essential roles in endocardial cushion formation, cardiomyocyte proliferation and survival. AB - Ezh2 is a histone trimethyltransferase that silences genes mainly via catalyzing trimethylation of histone 3 lysine 27 (H3K27Me3). The role of Ezh2 as a regulator of gene silencing and cell proliferation in cancer development has been extensively investigated; however, its function in heart development during embryonic cardiogenesis has not been well studied. In the present study, we used a genetically modified mouse system in which Ezh2 was specifically ablated in the mouse heart. We identified a wide spectrum of cardiovascular malformations in the Ezh2 mutant mice, which collectively led to perinatal death. In the Ezh2 mutant heart, the endocardial cushions (ECs) were hypoplastic and the endothelial-to mesenchymal transition (EMT) process was impaired. The hearts of Ezh2 mutant mice also exhibited decreased cardiomyocyte proliferation and increased apoptosis. We further identified that the Hey2 gene, which is important for cardiomyocyte proliferation and cardiac morphogenesis, is a downstream target of Ezh2. The regulation of Hey2 expression by Ezh2 may be independent of Notch signaling activity. Our work defines an indispensible role of the chromatin remodeling factor Ezh2 in normal cardiovascular development. PMID- 22312438 TI - Mimicry of food intake: the dynamic interplay between eating companions. AB - Numerous studies have shown that people adjust their intake directly to that of their eating companions; they eat more when others eat more, and less when others inhibit intake. A potential explanation for this modeling effect is that both eating companions' food intake becomes synchronized through processes of behavioral mimicry. No study, however, has tested whether behavioral mimicry can partially account for this modeling effect. To capture behavioral mimicry, real time observations of dyads of young females having an evening meal were conducted. It was assessed whether mimicry depended on the time of the interaction and on the person who took the bite. A total of 70 young female dyads took part in the study, from which the total number of bites (N = 3,888) was used as unit of analyses. For each dyad, the total number of bites and the exact time at which each person took a bite were coded. Behavioral mimicry was operationalized as a bite taken within a fixed 5-second interval after the other person had taken a bite, whereas non-mimicked bites were defined as bites taken outside the 5-second interval. It was found that both women mimicked each other's eating behavior. They were more likely to take a bite of their meal in congruence with their eating companion rather than eating at their own pace. This behavioral mimicry was found to be more prominent at the beginning than at the end of the interaction. This study suggests that behavioral mimicry may partially account for social modeling of food intake. PMID- 22312440 TI - Eradication of metastatic renal cell carcinoma after adenovirus-encoded TNF related apoptosis-inducing ligand (TRAIL)/CpG immunotherapy. AB - Despite evidence that antitumor immunity can be protective against renal cell carcinoma (RCC), few patients respond objectively to immunotherapy and the disease is fatal once metastases develop. We asked to what extent combinatorial immunotherapy with Adenovirus-encoded murine TNF-related apoptosis-inducing ligand (Ad5mTRAIL) plus CpG oligonucleotide, given at the primary tumor site, would prove efficacious against metastatic murine RCC. To quantitate primary renal and metastatic tumor growth in mice, we developed a luciferase-expressing Renca cell line, and monitored tumor burdens via bioluminescent imaging. Orthotopic tumor challenge gave rise to aggressive primary tumors and lung metastases that were detectable by day 7. Intra-renal administration of Ad5mTRAIL+CpG on day 7 led to an influx of effector phenotype CD4 and CD8 T cells into the kidney by day 12 and regression of established primary renal tumors. Intra-renal immunotherapy also led to systemic immune responses characterized by splenomegaly, elevated serum IgG levels, increased CD4 and CD8 T cell infiltration into the lungs, and elimination of metastatic lung tumors. Tumor regression was primarily dependent upon CD8 T cells and resulted in prolonged survival of treated mice. Thus, local administration of Ad5mTRAIL+CpG at the primary tumor site can initiate CD8-dependent systemic immunity that is sufficient to cause regression of metastatic lung tumors. A similar approach may prove beneficial for patients with metastatic RCC. PMID- 22312439 TI - Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families. AB - Pathogenic mutations in APP, PSEN1, PSEN2, MAPT and GRN have previously been linked to familial early onset forms of dementia. Mutation screening in these genes has been performed in either very small series or in single families with late onset AD (LOAD). Similarly, studies in single families have reported mutations in MAPT and GRN associated with clinical AD but no systematic screen of a large dataset has been performed to determine how frequently this occurs. We report sequence data for 439 probands from late-onset AD families with a history of four or more affected individuals. Sixty sequenced individuals (13.7%) carried a novel or pathogenic mutation. Eight pathogenic variants, (one each in APP and MAPT, two in PSEN1 and four in GRN) three of which are novel, were found in 14 samples. Thirteen additional variants, present in 23 families, did not segregate with disease, but the frequency of these variants is higher in AD cases than controls, indicating that these variants may also modify risk for disease. The frequency of rare variants in these genes in this series is significantly higher than in the 1,000 genome project (p = 5.09 * 10-5; OR = 2.21; 95%CI = 1.49-3.28) or an unselected population of 12,481 samples (p = 6.82 * 10-5; OR = 2.19; 95%CI = 1.347-3.26). Rare coding variants in APP, PSEN1 and PSEN2, increase risk for or cause late onset AD. The presence of variants in these genes in LOAD and early onset AD demonstrates that factors other than the mutation can impact the age at onset and penetrance of at least some variants associated with AD. MAPT and GRN mutations can be found in clinical series of AD most likely due to misdiagnosis. This study clearly demonstrates that rare variants in these genes could explain an important proportion of genetic heritability of AD, which is not detected by GWAS. PMID- 22312441 TI - Genetic association analysis using sibship data: a multilevel model approach. AB - Family based association study (FBAS) has the advantages of controlling for population stratification and testing for linkage and association simultaneously. We propose a retrospective multilevel model (rMLM) approach to analyze sibship data by using genotypic information as the dependent variable. Simulated data sets were generated using the simulation of linkage and association (SIMLA) program. We compared rMLM to sib transmission/disequilibrium test (S-TDT), sibling disequilibrium test (SDT), conditional logistic regression (CLR) and generalized estimation equations (GEE) on the measures of power, type I error, estimation bias and standard error. The results indicated that rMLM was a valid test of association in the presence of linkage using sibship data. The advantages of rMLM became more evident when the data contained concordant sibships. Compared to GEE, rMLM had less underestimated odds ratio (OR). Our results support the application of rMLM to detect gene-disease associations using sibship data. However, the risk of increasing type I error rate should be cautioned when there is association without linkage between the disease locus and the genotyped marker. PMID- 22312442 TI - S-LOCUS EARLY FLOWERING 3 is exclusively present in the genomes of short-styled buckwheat plants that exhibit heteromorphic self-incompatibility. AB - The different forms of flowers in a species have attracted the attention of many evolutionary biologists, including Charles Darwin. In Fagopyrum esculentum (common buckwheat), the occurrence of dimorphic flowers, namely short-styled and long-styled flowers, is associated with a type of self-incompatibility (SI) called heteromorphic SI. The floral morphology and intra-morph incompatibility are both determined by a single genetic locus named the S-locus. Plants with short-styled flowers are heterozygous (S/s) and plants with long-styled flowers are homozygous recessive (s/s) at the S-locus. Despite recent progress in our understanding of the molecular basis of flower development and plant SI systems, the molecular mechanisms underlying heteromorphic SI remain unresolved. By examining differentially expressed genes from the styles of the two floral morphs, we identified a gene that is expressed only in short-styled plants. The novel gene identified was completely linked to the S-locus in a linkage analysis of 1,373 plants and had homology to EARLY FLOWERING 3. We named this gene S-LOCUS EARLY FLOWERING 3 (S-ELF3). In an ion-beam-induced mutant that harbored a deletion in the genomic region spanning S-ELF3, a phenotype shift from short styled flowers to long-styled flowers was observed. Furthermore, S-ELF3 was present in the genome of short-styled plants and absent from that of long-styled plants both in world-wide landraces of buckwheat and in two distantly related Fagopyrum species that exhibit heteromorphic SI. Moreover, independent disruptions of S-ELF3 were detected in a recently emerged self-compatible Fagopyrum species and a self-compatible line of buckwheat. The nonessential role of S-ELF3 in the survival of individuals and the prolonged evolutionary presence only in the genomes of short-styled plants exhibiting heteromorphic SI suggests that S-ELF3 is a suitable candidate gene for the control of the short-styled phenotype of buckwheat plants. PMID- 22312443 TI - Innate sex differences in the timing of spring migration in a songbird. AB - In migrating animals protandry is the phenomenon whereby males of a species arrive at the breeding grounds earlier than females. In the present study we investigated the proximate causes of protandry in a migratory songbird, the northern wheatear Oenanthe oenanthe. Previous experiments with caged birds revealed that males and females show differentiated photoperiod-induced migratory habits. However, it remained open whether protandry would still occur without photoperiodic cues. In this study we kept captive first-year birds under constant photoperiod and environmental conditions in a "common garden" experiment. Male northern wheatears started their spring migratory activity earlier than females, even in the absence of environmental cues. This indicates that protandry in the northern wheatear has an endogenous basis with an innate earlier spring departure of males than females. PMID- 22312444 TI - Trans-synaptic spread of tau pathology in vivo. AB - Tauopathy in the brain of patients with Alzheimer's disease starts in the entorhinal cortex (EC) and spreads anatomically in a defined pattern. To test whether pathology initiating in the EC spreads through the brain along synaptically connected circuits, we have generated a transgenic mouse model that differentially expresses pathological human tau in the EC and we have examined the distribution of tau pathology at different timepoints. In relatively young mice (10-11 months old), human tau was present in some cell bodies, but it was mostly observed in axons within the superficial layers of the medial and lateral EC, and at the terminal zones of the perforant pathway. In old mice (>22 months old), intense human tau immunoreactivity was readily detected not only in neurons in the superficial layers of the EC, but also in the subiculum, a substantial number of hippocampal pyramidal neurons especially in CA1, and in dentate gyrus granule cells. Scattered immunoreactive neurons were also seen in the deeper layers of the EC and in perirhinal and secondary somatosensory cortex. Immunoreactivity with the conformation-specific tau antibody MC1 correlated with the accumulation of argyrophilic material seen in old, but not young mice. In old mice, axonal human tau immunoreactivity, especially at the endzones of the perforant pathway, was greatly reduced. Relocalization of tau from axons to somatodendritic compartments and propagation of tauopathy to regions outside of the EC correlated with mature tangle formation in neurons in the EC as revealed by thioflavin-S staining. Our data demonstrate propagation of pathology from the EC and support a trans-synaptic mechanism of spread along anatomically connected networks, between connected and vulnerable neurons. In general, the mouse recapitulates the tauopathy that defines the early stages of AD and provides a model for testing mechanisms and functional outcomes associated with disease progression. PMID- 22312445 TI - Tobacco rattle virus vector: A rapid and transient means of silencing manduca sexta genes by plant mediated RNA interference. AB - BACKGROUND: RNAi can be achieved in insect herbivores by feeding them host plants stably transformed to express double stranded RNA (dsRNA) of selected midgut expressed genes. However, the development of stably transformed plants is a slow and laborious process and here we developed a rapid, reliable and transient method. We used viral vectors to produce dsRNA in the host plant Nicotiana attenuata to transiently silence midgut genes of the plant's lepidopteran specialist herbivore, Manduca sexta. To compare the efficacy of longer, undiced dsRNA for insect gene silencing, we silenced N. attenuata's dicer genes (NaDCL1- 4) in all combinations in a plant stably transformed to express dsRNA targeting an insect gene. METHODOLOGY/PRINCIPAL FINDINGS: Stable transgenic N. attenuata plants harboring a 312 bp fragment of MsCYP6B46 in an inverted repeat orientation (ir-CYP6B46) were generated to produce CYP6B46 dsRNA. After consuming these plants, transcripts of CYP6B46 were significantly reduced in M. sexta larval midguts. The same 312 bp cDNA was cloned in an antisense orientation into a TRV vector and Agro-infiltrated into N. attenuata plants. When larvae ingested these plants, similar reductions in CYP6B46 transcripts were observed without reducing transcripts of the most closely related MsCYP6B45. We used this transient method to rapidly silence the expression of two additional midgut-expressed MsCYPs. CYP6B46 transcripts were further reduced in midguts, when the larvae fed on ir CYP6B46 plants transiently silenced for two combinations of NaDCLs (DCL1/3/4 and DCL2/3/4) and contained higher concentrations of longer, undiced CYP6B46 dsRNA. CONCLUSIONS: Both stable and transient expression of CYP6B46 dsRNA in host plants provides a specific and robust means of silencing this gene in M. sexta larvae, but the transient system is better suited for high throughput analyses. Transiently silencing NaDCLs in ir-CYP6B46 plants increased the silencing of MsCYP6B46, suggested that insect's RNAi machinery is more efficient with longer lengths of ingested dsRNA. PMID- 22312446 TI - Mitogen- and stress-activated kinase 1 (MSK1) regulates cigarette smoke-induced histone modifications on NF-kappaB-dependent genes. AB - Cigarette smoke (CS) causes sustained lung inflammation, which is an important event in the pathogenesis of chronic obstructive pulmonary disease (COPD). We have previously reported that IKKalpha (I kappaB kinase alpha) plays a key role in CS-induced pro-inflammatory gene transcription by chromatin modifications; however, the underlying role of downstream signaling kinase is not known. Mitogen and stress-activated kinase 1 (MSK1) serves as a specific downstream NF-kappaB RelA/p65 kinase, mediating transcriptional activation of NF-kappaB-dependent pro inflammatory genes. The role of MSK1 in nuclear signaling and chromatin modifications is not known, particularly in response to environmental stimuli. We hypothesized that MSK1 regulates chromatin modifications of pro-inflammatory gene promoters in response to CS. Here, we report that CS extract activates MSK1 in human lung epithelial (H292 and BEAS-2B) cell lines, human primary small airway epithelial cells (SAEC), and in mouse lung, resulting in phosphorylation of nuclear MSK1 (Thr581), phospho-acetylation of RelA/p65 at Ser276 and Lys310 respectively. This event was associated with phospho-acetylation of histone H3 (Ser10/Lys9) and acetylation of histone H4 (Lys12). MSK1 N- and C-terminal kinase dead mutants, MSK1 siRNA-mediated knock-down in transiently transfected H292 cells, and MSK1 stable knock-down mouse embryonic fibroblasts significantly reduced CS extract-induced MSK1, NF-kappaB RelA/p65 activation, and posttranslational modifications of histones. CS extract/CS promotes the direct interaction of MSK1 with RelA/p65 and p300 in epithelial cells and in mouse lung. Furthermore, CS-mediated recruitment of MSK1 and its substrates to the promoters of NF-kappaB-dependent pro-inflammatory genes leads to transcriptional activation, as determined by chromatin immunoprecipitation. Thus, MSK1 is an important downstream kinase involved in CS-induced NF-kappaB activation and chromatin modifications, which have implications in pathogenesis of COPD. PMID- 22312447 TI - Knowledge-based reconstruction of mRNA transcripts with short sequencing reads for transcriptome research. AB - While most transcriptome analyses in high-throughput clinical studies focus on gene level expression, the existence of alternative isoforms of gene transcripts is a major source of the diversity in the biological functionalities of the human genome. It is, therefore, essential to annotate isoforms of gene transcripts for genome-wide transcriptome studies. Recently developed mRNA sequencing technology presents an unprecedented opportunity to discover new forms of transcripts, and at the same time brings bioinformatic challenges due to its short read length and incomplete coverage for the transcripts. In this work, we proposed a computational approach to reconstruct new mRNA transcripts from short sequencing reads with reference information of known transcripts in existing databases. The prior knowledge helped to define exon boundaries and fill in the transcript regions not covered by sequencing data. This approach was demonstrated using a deep sequencing data set of human muscle tissue with transcript annotations in RefSeq as prior knowledge. We identified 2,973 junctions, 7,471 exons, and 7,571 transcripts not previously annotated in RefSeq. 73% of these new transcripts found supports from UCSC Known Genes, Ensembl or EST transcript annotations. In addition, the reconstructed transcripts were much longer than those from de novo approaches that assume no prior knowledge. These previously un-annotated transcripts can be integrated with known transcript annotations to improve both the design of microarrays and the follow-up analyses of isoform expression. The overall results demonstrated that incorporating transcript annotations from genomic databases significantly helps the reconstruction of novel transcripts from short sequencing reads for transcriptome research. PMID- 22312448 TI - CenSeam, an International Program on Seamounts within the Census of Marine Life: achievements and lessons learned. PMID- 22312449 TI - Overview of screening methods for fatty liver disease in children. AB - The prevalence of obesity and obesity related comorbidities including diabetes and nonalcoholic fatty liver disease (NAFLD) has been rising globally. Nonalcoholic fatty liver disease is emerging as a common liver disease among adults which can lead to the eventual development of complications including cirrhosis and hepatocellular carcinoma. With the rise of obesity in children, the development of detection methods for the presence of NAFLD is becoming imperative. Although the gold standard for diagnosis is liver biopsy, practical issues limit pediatric use and warrant development of noninvasive or minimally invasive screening tools for the detection and staging of NAFLD. A variety of diagnostic methods have been studied including use aminotransferases, imaging studies and serologic markers which have some population-based limitations. Additional factors such as gender and ethnicity may also play a role in the screening of NAFLD in pediatric population studies. PMID- 22312450 TI - Liver transplantation for Wilson disease. AB - The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD. PMID- 22312451 TI - Elevation of the glycated albumin to glycated hemoglobin ratio during the progression of hepatitis C virus related liver fibrosis. AB - AIM: To analyze the relationship between the glycated albumin (GA) to glycated hemoglobin (HbA1c) ratio and the histological grading of liver fibrosis. METHODS: The study retrospectively included consecutive hepatitis C virus positive chronic liver disease patients (n = 142) who had undergone percutaneous liver biopsy between January 2008 and March 2010 at our institution. The ratios of GA/HbA1c were calculated in all patients to investigate the relationship with the degree of the liver fibrosis. The values of the aspartate aminotransferase-to-platelet ratio index (APRI), an excellent marker for the evaluation of liver fibrosis, were also calculated. In addition, we combined the ratio of GA/HbA1c and the APRI in order to improve our ability to detect the presence of significant liver fibrosis. RESULTS: Sixty-one (43%) patients had either no fibrosis or minimal fibrosis (METAVIR score: F0-F1), while 25 (17%) had intermediate fibrosis (F2). Fifty-six (39%) patients had severe fibrosis (F3-F4) and 27 of them had cirrhosis (F4). The mean values of the GA/HbA1c increased with the progression of the fibrosis (F0-1: 2.83 +/- 0.24, F2: 2.85 +/- 0.24, F3: 2.92 +/- 0.35, F4: 3.14 +/- 0.54). There was a significant difference between the F0-F1 vs F4, F2 vs F4, and F3 vs F4 groups (P < 0.01, P < 0.01, P < 0.01 and P < 0.05, respectively). The GA/HbA1c ratio was significantly higher in the patients with cirrhosis (F4) than in those without cirrhosis (F0-F3) (3.14 +/- 0.54 vs 2.85 +/- 0.28, P < 0.0001). The GA/HbA1c ratio was also significantly higher in the patients with severe fibrosis (F3-F4) than in those without severe liver fibrosis (F0-F2) (3.03 +/- 0.41 vs 2.84 +/- 0.24, P < 0.001). Furthermore, the GA/HbA1c ratio was also significantly higher in the patients with significant fibrosis (F2-F4) than in those without significant liver fibrosis (F0-F1) (2.98 +/- 0.41 vs 2.83 +/- 0.24, P < 0.001). The diagnostic performance of the increased GA/HbA1c ratio (> 3.0) was as follows: its sensitivity and specificity for the detection of liver cirrhosis (F4) were 59.3% and 70.4%, respectively and its sensitivity and specificity for the detection of severe liver fibrosis (F3-F4) were 50.0% and 74.4%, respectively. With regard to the detection of significant fibrosis (F2 F4), its sensitivity was 44.4% and its specificity was 77.0%. Although even the excellent marker APRI shows low sensitivity (25.9%) for distinguishing patients with or without significant fibrosis, the combination of the APRI and GA/HbA1c ratio increased the sensitivity up to 42.0%, with only a modest decrease in the specificity (from 90.2% to 83.6%). CONCLUSION: The GA/HbA1c ratio increased in line with the histological severity of liver fibrosis, thus suggesting that this ratio is useful as a supportive index of liver fibrosis. PMID- 22312452 TI - Autophagy in mammalian cells. AB - Autophagy is a regulated process for the degradation of cellular components that has been well conserved in eukaryotic cells. The discovery of autophagy regulating proteins in yeast has been important in understanding this process. Although many parallels exist between fungi and mammals in the regulation and execution of autophagy, there are some important differences. The pre autophagosomal structure found in yeast has not been identified in mammals, and it seems that there may be multiple origins for autophagosomes, including endoplasmic reticulum, plasma membrane and mitochondrial outer membrane. The maturation of the phagophore is largely dependent on 5'-AMP activated protein kinase and other factors that lead to the dephosphorylation of mammalian target of rapamycin. Once the process is initiated, the mammalian phagophore elongates and matures into an autophagosome by processes that are similar to those in yeast. Cargo selection is dependent on the ubiquitin conjugation of protein aggregates and organelles and recognition of these conjugates by autophagosomal receptors. Lysosomal degradation of cargo produces metabolites that can be recycled during stress. Autophagy is an important cellular safeguard during starvation in all eukaryotes; however, it may have more complicated, tissue specific roles in mammals. With certain exceptions, autophagy seems to be cytoprotective, and defects in the process have been associated with human disease. PMID- 22312453 TI - Yeast nuclear RNA processing. AB - Nuclear RNA processing requires dynamic and intricately regulated machinery composed of multiple enzymes and their cofactors. In this review, we summarize recent experiments using Saccharomyces cerevisiae as a model system that have yielded important insights regarding the conversion of pre-RNAs to functional RNAs, and the elimination of aberrant RNAs and unneeded intermediates from the nuclear RNA pool. Much progress has been made recently in describing the 3D structure of many elements of the nuclear degradation machinery and its cofactors. Similarly, the regulatory mechanisms that govern RNA processing are gradually coming into focus. Such advances invariably generate many new questions, which we highlight in this review. PMID- 22312454 TI - Protein-protected luminescent noble metal quantum clusters: an emerging trend in atomic cluster nanoscience. AB - Noble metal quantum clusters (NMQCs) are the missing link between isolated noble metal atoms and nanoparticles. NMQCs are sub-nanometer core sized clusters composed of a group of atoms, most often luminescent in the visible region, and possess intriguing photo-physical and chemical properties. A trend is observed in the use of ligands, ranging from phosphines to functional proteins, for the synthesis of NMQCs in the liquid phase. In this review, we briefly overview recent advancements in the synthesis of protein protected NMQCs with special emphasis on their structural and photo-physical properties. In view of the protein protection, coupled with direct synthesis and easy functionalization, this hybrid QC-protein system is expected to have numerous optical and bioimaging applications in the future, pointers in this direction are visible in the literature. PMID- 22312455 TI - Comparative Study on Biochemical Properties and Antioxidative Activity of Cuttlefish (Sepia officinalis) Protein Hydrolysates Produced by Alcalase and Bacillus licheniformis NH1 Proteases. AB - Antioxidative activities and biochemical properties of protein hydrolysates prepared from cuttlefish (Sepia officinalis) using Alcalase 2.4 L and Bacillus licheniformis NH1 proteases with different degrees of hydrolysis (DH) were determined. For the biochemical properties, hydrolysis by both enzymes increased protein solubility to above 75% over a wide pH range. The antioxidant activities of cuttlefish protein hydrolysates (CPHs) increase with increasing DH. In addition, all CPHs exhibited antioxidative activity in a concentration-dependent manner. NH1-CPHs generally showed greater antioxidative activity than Alcalase protein hydrolysates (P < 0.05) as indicated by the higher 1,1-diphenyl-1 picryhydrazyl (DPPH) radical scavenging activity and ferrous chelating activity. Both Alcalase and NH1 protein hydrolysates were able to retard lipid peroxidation and beta-carotene-linoleic acid oxidation. Alcalase-CPH (DH = 12.5%) and NH1-CPH (DH = 15%) contained 75.36% and 80.11% protein, respectively, with histidine and arginine as the major amino acids, followed by glutamic acid/glutamine, serine, lysine, and leucine. In addition, CPHs have a high percentage of essential amino acids made up 48.85% and 50.04%. Cuttlefish muscle protein hydrolysates had a high nutritional value and could be used as supplement to poorly balanced dietary proteins. PMID- 22312456 TI - Methionine-35 of abeta(1-42): importance for oxidative stress in Alzheimer disease. AB - Alzheimer disease (AD) is an age-related progressive neurodegenerative disorder. This devastating disease is characterized by the presence of senile plaques (SP), neurofibrillary tangles (NFTs), and loss of synapses. Amyloid beta-peptide 1-42 (Abeta(1-42)) is the main component of SP and is pivotal to AD pathogenesis. Brain of subjects with AD and arguably its earliest manifestation, mild cognitive impairment (MCI), demonstrate increased levels of oxidative stress markers. Our laboratory combined these two aspects of AD and MCI and proposed the Abeta(1-42) associated free radical oxidative stress hypothesis to explain oxidative stress under which the MCI and AD brain exist and the loss of synapses in both disorders. A large number of in vitro and in vivo studies showed that Abeta causes protein oxidation, lipid peroxidation, reactive oxygen species formation, and cell death in neuronal and synaptosomal systems. Methionine located at residue 35 of Abeta(1-42) is an important contributor to the oxidative stress associated with this neurotoxic peptide. In this paper, we summarize studies involving Met-35 of Abeta(1-42). Understanding the role of the single methionine residue of Abeta(1-42) may help in understanding underlying disease mechanisms in AD and MCI. PMID- 22312457 TI - Small changes huge impact: the role of protein posttranslational modifications in cellular homeostasis and disease. AB - Posttranslational modifications (PTMs) modulate protein function in most eukaryotes and have a ubiquitous role in diverse range of cellular functions. Identification, characterization, and mapping of these modifications to specific amino acid residues on proteins are critical towards understanding their functional significance in a biological context. The interpretation of proteome data obtained from the high-throughput methods cannot be deciphered unambiguously without a priori knowledge of protein modifications. An in-depth understanding of protein PTMs is important not only for gaining a perception of a wide array of cellular functions but also towards developing drug therapies for many life threatening diseases like cancer and neurodegenerative disorders. Many of the protein modifications like ubiquitination play a decisive role in various drug response(s) and eventually in disease prognosis. Thus, many commonly observed PTMs are routinely tracked as disease markers while many others are used as molecular targets for developing target-specific therapies. In this paper, we summarize some of the major, well-studied protein alterations and highlight their importance in various chronic diseases and normal development. In addition, other promising minor modifications such as SUMOylation, observed to impact cellular dynamics as well as disease pathology, are mentioned briefly. PMID- 22312458 TI - Intracisternally injected L-proline activates hypothalamic supraoptic, but not paraventricular, vasopressin-expressing neurons in conscious rats. AB - When injected into specific rat brain regions, the neurotransmitter candidate L proline produces various cardiovascular changes through ionotropic excitatory amino acid receptors. The present study used an immunohistochemical double labeling approach to determine whether intracisternally injected L-proline in freely moving rats, which increases blood pressure, activates hypothalamic vasopressin-expressing neurons and ventral medullary tyrosine-hydroxylase- (TH-) containing neurons. Following injection of L-proline, the number of activated hypothalamic neurons that coexpressed vasopressin and c-Fos was much greater in the supraoptic nucleus (SON) than in the paraventricular nucleus (PVN) of rats with increased blood pressure. The number of activated TH-containing neurons was significantly greater following L-proline treatment than following control injections of artificial cerebrospinal fluid (ACSF). These results clearly demonstrate that intracisternally injected L-proline activates hypothalamic supraoptic, but not paraventricular, vasopressin-expressing neurons and medullary TH-containing (A1/C1) neurons in freely moving rats. PMID- 22312459 TI - The Aggregation Inhibitor Peptide QBP1 as a Therapeutic Molecule for the Polyglutamine Neurodegenerative Diseases. AB - Misfolding and abnormal aggregation of proteins in the brain are implicated in the pathogenesis of various neurodegenerative diseases including Alzheimer's, Parkinson's, and the polyglutamine (polyQ) diseases. In the polyQ diseases, an abnormally expanded polyQ stretch triggers misfolding and aggregation of the disease-causing proteins, eventually resulting in neurodegeneration. In this paper, we introduce our therapeutic strategy against the polyQ diseases using polyQ binding peptide 1 (QBP1), a peptide that we identified by phage display screening. We showed that QBP1 specifically binds to the expanded polyQ stretch and inhibits its misfolding and aggregation, resulting in suppression of neurodegeneration in cell culture and animal models of the polyQ diseases. We further demonstrated the potential of protein transduction domains (PTDs) for in vivo delivery of QBP1. We hope that in the near future, chemical analogues of aggregation inhibitor peptides including QBP1 will be developed against protein misfolding-associated neurodegenerative diseases. PMID- 22312460 TI - The Importance of GLWamide Neuropeptides in Cnidarian Development and Physiology. AB - The peptide-signaling molecules (<50 amino acid residues) occur in a wide variety of invertebrate and vertebrate organisms, playing pivotal roles in physiological, endocrine, and developmental processes. While some of these peptides display similar structures in mammals and invertebrates, others differ with respect to their structure and function in a species-specific manner. Such a conservation of basic structure and function implies that many peptide-signaling molecules arose very early in the evolutionary history of some taxa, while species-specific characteristics led us to suggest that they also acquire the ability to evolve in response to specific environmental conditions. In this paper, we describe GLWamide-family peptides that function as signaling molecules in the process of muscle contraction, metamorphosis, and settlement in cnidarians. The peptides are produced by neurons and are therefore referred to as neuropeptides. We discuss the importance of the neuropeptides in both developmental and physiological processes in a subset of hydrozoans, as well as the potential use as a seed compound in drug development and aspects related to the protection of corals. PMID- 22312461 TI - Peptides regulate cortical thymocytes differentiation, proliferation, and apoptosis. AB - The processes of differentiation, proliferation, and apoptosis were studied in a cell culture of human cortical thymocytes under the influence of short peptides T 32 (Glu-Asp-Ala) and T-38 (Lys-Glu-Asp). Peptides T-32 and T-38 amplified cortical thymocytes differentiation towards regulatory T cells, increased their proliferative activity, and decreased the level of apoptosis. Moreover, peptides under study stimulated proliferative and antiapoptotic activity of the mature regulatory T cells. PMID- 22312462 TI - Functionally Relevant Residues of Cdr1p: A Multidrug ABC Transporter of Human Pathogenic Candida albicans. AB - Reduced intracellular accumulation of drugs (due to rapid efflux) mediated by the efflux pump proteins belonging to ABC (ATP Binding Cassette) and MFS (Major Facilitators) superfamily is one of the most common strategies adopted by multidrug resistance (MDR) pathogenic yeasts. To combat MDR, it is essential to understand the structure and function of these transporters so that inhibitors/modulators to these can be developed. The sequence alignments of the ABC transporters reveal selective divergence within much conserved domains of Nucleotide-Binding Domains (NBDs) which is unique to all fungal transporters. Recently, the role of conserved but divergent residues of Candida Drug Resistance 1 (CDR1), an ABC drug transporter of human pathogenic Candida albicans, has been examined with regard to ATP binding and hydrolysis. In this paper, we focus on some of the recent advances on the relevance of divergent and conserved amino acids of CaCdr1p and also discuss as to how drug interacts with Trans Membrane Domains (TMDs) residues for its extrusion from MDR cells. PMID- 22312463 TI - Metal preferences of zinc-binding motif on metalloproteases. AB - Almost all naturally occurring metalloproteases are monozinc enzymes. The zinc in any number of zinc metalloproteases has been substituted by some other divalent cation. Almost all Co(II)- or Mn(II)-substituted enzymes maintain the catalytic activity of their zinc counterparts. However, in the case of Cu(II) substitution of zinc proteases, a great number of enzymes are not active, for example, thermolysin, carboxypeptidase A, endopeptidase from Lactococcus lactis, or aminopeptidase B, while some do have catalytic activity, for example, astacin (37%) and DPP III (100%). Based on structural studies of various metal substituted enzymes, for example, thermolysin, astacin, aminopeptidase B, dipeptidyl peptidase (DPP) III, and del-DPP III, the metal coordination geometries of both active and inactive Cu(II)-substituted enzymes are shown to be the same as those of the wild-type Zn(II) enzymes. Therefore, the enzyme activity of a copper-ion-substituted zinc metalloprotease may depend on the flexibility of catalytic domain. PMID- 22312464 TI - Proteins and enzymes from marine resources. PMID- 22312465 TI - Functional residues in proteins. PMID- 22312466 TI - Serpin Inhibition Mechanism: A Delicate Balance between Native Metastable State and Polymerization. AB - The serpins (serine proteinase inhibitors) are structurally similar but functionally diverse proteins that fold into a conserved structure and employ a unique suicide substrate-like inhibitory mechanism. Serpins play absolutely critical role in the control of proteases involved in the inflammatory, complement, coagulation and fibrinolytic pathways and are associated with many conformational diseases. Serpin's native state is a metastable state which transforms to a more stable state during its inhibitory mechanism. Serpin in the native form is in the stressed (S) conformation that undergoes a transition to a relaxed (R) conformation for the protease inhibition. During this transition the region called as reactive center loop which interacts with target proteases, inserts itself into the center of beta-sheet A to form an extra strand. Serpin is delicately balanced to perform its function with many critical residues involved in maintaining metastability. However due to its typical mechanism of inhibition, naturally occurring serpin variants produces conformational instability that allows insertion of RCL of one molecule into the beta-sheet A of another to form a loop-sheet linkage leading to its polymerization and aggregation. Thus understanding the molecular basis and amino acid involved in serpin polymerization mechanism is critical to devising strategies for its cure. PMID- 22312468 TI - Mackerel trypsin purified from defatted viscera by supercritical carbon dioxide. AB - Viscera of mackerel (Scomber sp.) were defatted by supercritical carbon dioxide (SCO(2)) treatment. Trypsin (SC-T) was then extracted from the defatted powder and purified by a series of chromatographies including Sephacryl S-200 and Sephadex G-50. The purified SC-T was nearly homogeneous on SDS-PAGE, and its molecular weight was estimated as approximately 24,000 Da. N-terminal twenty amino acids sequence of SC-T was IVGGYECTAHSQPHQVSLNS. The specific trypsin inhibitors, soybean trypsin inhibitor and TLCK, strongly inhibited the activities of SC-T. The pH and temperature optimums of SC-T were at around pH 8.0 and 60 degrees C, respectively, using N(alpha)-p-tosyl-L-arginine methyl ester as a substrate. The SC-T was unstable below pH 5.0 and above 40 degrees C, and it was stabilized by calcium ion. These enzymatic characteristics of SC-T were the same as those of other fish trypsins, especially spotted mackerel (S. borealis) trypsin, purified from viscera defatted by acetone. Therefore, we concluded that the SCO(2) defatting process is useful as a substitute for organic solvent defatting process. PMID- 22312467 TI - Signal protein-derived peptides as functional probes and regulators of intracellular signaling. AB - The functionally important regions of signal proteins participating in their specific interaction and responsible for transduction of hormonal signal into cell are rather short in length, having, as a rule, 8 to 20 amino acid residues. Synthetic peptides corresponding to these regions are able to mimic the activated form of full-size signal protein and to trigger signaling cascades in the absence of hormonal stimulus. They modulate protein-protein interaction and influence the activity of signal proteins followed by changes in their regulatory and catalytic sites. The present review is devoted to the achievements and perspectives of the study of signal protein-derived peptides and to their application as selective and effective regulators of hormonal signaling systems in vitro and in vivo. Attention is focused on the structure, biological activity, and molecular mechanisms of action of peptides, derivatives of the receptors, G protein alpha subunits, and the enzymes generating second messengers. PMID- 22312469 TI - Dicer functions in aquatic species. AB - Dicer is an RNase III enzyme with two catalytic subunits, which catalyzes the cleavage of double-stranded RNA to small interfering RNAs and micro-RNAs, which are mainly involved in invasive nucleic acid defense and endogenous genes regulation. Dicer is abundantly expressed in embryos, indicating the importance of the protein in early embryonic development. In addition, Dicer is thought to be involved in defense mechanism against foreign nucleic acids such as viruses. This paper will mainly focus on the recent progress of Dicer-related research and discuss potential RNA interference pathways in aquatic species. PMID- 22312470 TI - Role of Charged Residues in the Catalytic Sites of Escherichia coli ATP Synthase. AB - Here we describe the role of charged amino acids at the catalytic sites of Escherichia coli ATP synthase. There are four positively charged and four negatively charged residues in the vicinity of of E. coli ATP synthase catalytic sites. Positive charges are contributed by three arginine and one lysine, while negative charges are contributed by two aspartic acid and two glutamic acid residues. Replacement of arginine with a neutral amino acid has been shown to abrogate phosphate binding, while restoration of phosphate binding has been accomplished by insertion of arginine at the same or a nearby location. The number and position of positive charges plays a critical role in the proper and efficient binding of phosphate. However, a cluster of many positive charges inhibits phosphate binding. Moreover, the presence of negatively charged residues seems a requisite for the proper orientation and functioning of positively charged residues in the catalytic sites. This implies that electrostatic interactions between amino acids are an important constituent of initial phosphate binding in the catalytic sites. Significant loss of function in growth and ATPase activity assays in mutants generated through charge modulations has demonstrated that precise location and stereochemical interactions are of paramount importance. PMID- 22312471 TI - The dynamic structure of the estrogen receptor. AB - The estrogen receptor (ER) mediates most of the biological effects of estrogens at the level of gene regulation by interacting through its site-specific DNA and with other coregulatory proteins. In recent years, new information regarding the dynamic structural nature of ER has emerged. The physiological effects of estrogen are manifested through ER's two isoforms, ER(alpha) and ER(beta). These two isoforms (ER(alpha) and ER(beta)) display distinct regions of sequence homology. The three-dimensional structures of the DNA-binding domain (DBD) and ligand-binding domain (LBD) have been solved, whereas no three-dimensional natively folded structure for the ER N-terminal domain (NTD) is available to date. However, insights about the structural and functional correlations regarding the ER NTD have recently emerged. In this paper, we discuss the knowledge about the structural characteristics of the ER in general and how the structural features of the two isoforms differ, and its subsequent role in gene regulation. PMID- 22312472 TI - NOP Receptor Ligands as Potential Agents for Inflammatory and Autoimmune Diseases. AB - Nociceptin/orphanin FQ (N/OFQ) is a seventeen-amino acid peptide that is the endogenous ligand of a G-protein-coupled receptor (NOP). Various immune cells express the precursor protein and secrete N/OFQ as well as display binding sites for this peptide. The functional capacity of NOP receptor was demonstrated in vitro and in vivo studies by the ability of N/OFQ to induce chemotaxis of immune cells, to regulate the expression of cytokines and other inflammatory mediators, and to control cellular and humoral immunity. In this context, N/OFQ could modulate the outcome of some inflammatory diseases, such as sepsis and autoimmune pathologies by mechanisms not clearly elucidated yet. In fact, human body fluid revealed increased levels of N/OFQ under sepsis, arthritis, and Parkinson's diagnose. Preclinical studies pointed to the blockade of NOP receptor signaling as successful in treating these experimental conditions. Further preclinical and clinical studies are required to investigate the potential of NOP ligands in treating inflammatory diseases. PMID- 22312473 TI - Diversified carbohydrate-binding lectins from marine resources. AB - Marine bioresources produce a great variety of specific and potent bioactive molecules including natural organic compounds such as fatty acids, polysaccharides, polyether, peptides, proteins, and enzymes. Lectins are also one of the promising candidates for useful therapeutic agents because they can recognize the specific carbohydrate structures such as proteoglycans, glycoproteins, and glycolipids, resulting in the regulation of various cells via glycoconjugates and their physiological and pathological phenomenon through the host-pathogen interactions and cell-cell communications. Here, we review the multiple lectins from marine resources including fishes and sea invertebrate in terms of their structure-activity relationships and molecular evolution. Especially, we focus on the unique structural properties and molecular evolution of C-type lectins, galectin, F-type lectin, and rhamnose-binding lectin families. PMID- 22312475 TI - Simple preparation of pacific cod trypsin for enzymatic Peptide synthesis. AB - Trypsin from the pyloric caeca of Pacific cod (Gadus macrocephalus) was easily prepared by affinity chromatography on Benzamidine Sepharose 6B and gel filtration on Superdex 75. Pacific cod trypsin was composed of three isozymes, and their molecular masses were estimated 23,756.34 Da, 23,939.62 Da, and 24,114.81 Da by desorption/ionization time-of-flight mass spectroscopy (MALDI/TOF MS) and their isoelectric points (pIs) were approximately 5.1, 6.0, and 6.2, respectively. The isolated Pacific cod trypsin showed high similarity to other frigid-zone fish trypsins. The kinetic behavior of tryptic hydrolysis toward N-p tosyl-L-arginine methyl ester hydrochloride (TAME), N-benzoyl-L-arginine p nitroanilide hydrochloride (BAPA), and p-amidinophenyl ester were also analyzed. In addition, the cod trypsin-catalyzed dipeptide synthesis was investigated using twelve series of "inverse subdtrates" that is p- and m-isomer of amidinophenyl, guanidinophenyl, (amidinomethyl)phenyl, (guanidinomethyl)phenyl, and four position isomers of guanidinonaphtyl esters derived from N-(tert butoxycarbonyl)amino acid as acyl donor components. They were found to couple with an acyl acceptor such as L-alanine p-nitroanilide to produce dipeptide in the presence of the trypsin. All inverse substrates tested in this study undergo less enantioselective coupling reaction. The p-guanidinophenyl ester was most practical substrate in twelve series tested. The enzymatic hydrolysis of the resulting products was negligible. PMID- 22312476 TI - Digestive Alkaline Proteases from Zosterisessor ophiocephalus, Raja clavata, and Scorpaena scrofa: Characteristics and Application in Chitin Extraction. AB - The aim of this work was to study some biochemical characteristics of crude alkaline protease extracts from the viscera of goby (Zosterisessor ophiocephalus), thornback ray (Raja clavata), and scorpionfish (Scorpaena scrofa), and to investigate their applications in the deproteinization of shrimp wastes. At least four caseinolytic proteases bands were observed in zymogram of each enzyme preparation. The optimum pH for enzymatic extracts activities of Z. ophiocephalus, R. clavata, and S. scrofa were 8.0-9.0, 8.0, and 10.0, respectively. Interestingly, all the enzyme preparations were highly stable over a wide range of pH from 6.0 to 11.0. The optimum temperatures for enzyme activity were 50 degrees C for Z. ophiocephalus and R. clavata and 55 degrees C for S. scrofa crude alkaline proteases. Proteolytic enzymes showed high stability towards non-ionic surfactants (5% Tween 20, Tween 80, and Triton X-100). In addition, crude proteases of S. scrofa, R. clavata, and Z. ophiocephalus were found to be highly stable towards oxidizing agents, retaining 100%, 70%, and 66%, respectively, of their initial activity after incubation for 1 h in the presence of 1% sodium perborate. They were, however, highly affected by the anionic surfactant SDS. The crude alkaline proteases were tested for the deproteinization of shrimp waste in the preparation of chitin. All proteases were found to be effective in the deproteinization of shrimp waste. The protein removals after 3 h of hydrolysis at 45 degrees C with an enzyme/substrate ratio (E/S) of 10 were about 76%, 76%, and 80%, for Z. ophiocephalus, R. clavata, and S. scrofa crude proteases, respectively. These results suggest that enzymatic deproteinization of shrimp wastes by fish endogenous alkaline proteases could be applicable to the chitin production process. PMID- 22312474 TI - Functional Subunits of Eukaryotic Chaperonin CCT/TRiC in Protein Folding. AB - Molecular chaperones are a class of proteins responsible for proper folding of a large number of polypeptides in both prokaryotic and eukaryotic cells. Newly synthesized polypeptides are prone to nonspecific interactions, and many of them make toxic aggregates in absence of chaperones. The eukaryotic chaperonin CCT is a large, multisubunit, cylindrical structure having two identical rings stacked back to back. Each ring is composed of eight different but similar subunits and each subunit has three distinct domains. CCT assists folding of actin, tubulin, and numerous other cellular proteins in an ATP-dependent manner. The catalytic cooperativity of ATP binding/hydrolysis in CCT occurs in a sequential manner different from concerted cooperativity as shown for GroEL. Unlike GroEL, CCT does not have GroES-like cofactor, rather it has a built-in lid structure responsible for closing the central cavity. The CCT complex recognizes its substrates through diverse mechanisms involving hydrophobic or electrostatic interactions. Upstream factors like Hsp70 and Hsp90 also work in a concerted manner to transfer the substrate to CCT. Moreover, prefoldin, phosducin-like proteins, and Bag3 protein interact with CCT and modulate its function for the fine-tuning of protein folding process. Any misregulation of protein folding process leads to the formation of misfolded proteins or toxic aggregates which are linked to multiple pathological disorders. PMID- 22312477 TI - Structure and dynamics of dinucleosomes assessed by atomic force microscopy. AB - Dynamics of nucleosomes and their interactions are important for understanding the mechanism of chromatin assembly. Internucleosomal interaction is required for the formation of higher-order chromatin structures. Although H1 histone is critically involved in the process of chromatin assembly, direct internucleosomal interactions contribute to this process as well. To characterize the interactions of nucleosomes within the nucleosome array, we designed a dinucleosome and performed direct AFM imaging. The analysis of the AFM data showed dinucleosomes are very dynamic systems, enabling the nucleosomes to move in a broad range along the DNA template. Di-nucleosomes in close proximity were observed, but their population was low. The use of the zwitterionic detergent, CHAPS, increased the dynamic range of the di-nucleosome, facilitating the formation of tight di nucleosomes. The role of CHAPS and similar natural products in chromatin structure and dynamics is also discussed. PMID- 22312478 TI - Role of Linkers between Zinc Fingers in Spacing Recognition by Plant TFIIIA-Type Zinc-Finger Proteins. AB - The EPF family of plant TFIIIA-type zinc-finger (ZF) proteins (ZPTs) is characterized by long linkers separating ZF motifs. We previously reported that two-fingered ZPTs bind to two tandem core sites that are separated by several base pairs, each ZF making contact with one core site. Here we report further characterization of DNA-binding activities of ZPTs using four family members, ZPT2-14, ZPT2-7, ZPT2-8, and ZPT2-2, having inter-ZF linkers of different lengths and sequences, to investigate the correlation of the length and/or sequence of the linker with preference for the spacing between core sites in target DNAs. Selected and amplified binding site (SAAB)-imprinting assays and gel mobility shift assays prompted three conclusions. (1) The four ZPTs have common specificity for core binding sites-two AGT(G)/(C)ACTs separated by several nucleotides. (2) The four ZPTs prefer a spacing of 10 bases between the core sites, but each ZPT has its own preference for suboptimal spacing. (3) At a particular spacing, two zinc fingers may bind to the core sites on both strands. The results provide new information about how the diversity in linker length/sequence affects DNA-sequence recognition in this protein family. PMID- 22312479 TI - Myasthenia gravis. PMID- 22312482 TI - Sensory neuronopathy and autoimmune diseases. AB - Sensory neuronopathies (SNs) are a specific subgroup of peripheral nervous system diseases characterized by primary degeneration of dorsal root ganglia and their projections. Multifocal sensory symptoms often associated to ataxia are the classical features of SN. Several different etiologies have been described for SNs, but immune-mediated damage plays a key role in most cases. SN may herald the onset of some systemic autoimmune diseases, which further emphasizes how important the recognition of SN is in clinical practice. We have thus reviewed available clinical, neurophysiological, and therapeutic data on autoimmune disease-related SN, namely, in patients with Sjogren's syndrome, autoimmune hepatitis, and celiac disease. PMID- 22312483 TI - Humidification performance of heat and moisture exchangers for pediatric use. AB - Background. While heat and moisture exchangers (HMEs) have been increasingly used for humidification during mechanical ventilation, the efficacy of pediatric HMEs has not yet been fully evaluated. Methods. We tested ten pediatric HMEs when mechanically ventilating a model lung at respiratory rates of 20 and 30 breaths/min and pressure control of 10, 15, and 20 cmH(2)O. The expiratory gas passed through a heated humidifier. We created two rates of leakage: 3.2 L/min (small) and 5.1 L/min (large) when pressure was 10 cmH(2)O. We measured absolute humidity (AH) at the Y-piece. Results. Without leakage, eight of ten HMEs maintained AH at more than 30 mg/L. With the small leak, AH decreased below 30 mg/L (26.6 to 29.5 mg/L), decreasing further (19.7 to 27.3 mg/L) with the large leak. Respiratory rate and pressure control level did not affect AH values. Conclusions. Pediatric HMEs provide adequate humidification performance when leakage is absent. PMID- 22312484 TI - Characterization of bacterial etiologic agents of biofilm formation in medical devices in critical care setup. AB - Background. Biofilms contaminate catheters, ventilators, and medical implants; they act as a source of disease for humans, animals, and plants. Aim. Critical care units of any healthcare institute follow various interventional strategies with use of medical devices for the management of critical cases. Bacteria contaminate medical devices and form biofilms. Material and Methods. The study was carried out on 100 positive bacteriological cultures of medical devices which were inserted in hospitalized patients. The bacterial isolates were processed as per microtitre plate. All the isolates were subjected to antibiotic susceptibility testing by VITEK 2 compact automated systems. Results. Out of the total 100 bacterial isolates tested, 88 of them were biofilm formers. A 16-20 hour incubation period was found to be optimum for biofilm development. 85% isolates were multidrug resistants and different mechanisms of bacterial drug resistance like ESBL, carbapenemase, and MRSA were found among isolates. Conclusion. Availability of nutrition in the form of glucose enhances the biofilm formation by bacteria. Time and availability of glucose are important factors for assessment of biofilm progress. It is an alarm for those who are associated with invasive procedures and indwelling medical devices especially in patients with low immunity. PMID- 22312480 TI - CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis. AB - CD8+ T-cell deficiency is a feature of many chronic autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, systemic sclerosis, dermatomyositis, primary biliary cirrhosis, primary sclerosing cholangitis, ulcerative colitis, Crohn's disease, psoriasis, vitiligo, bullous pemphigoid, alopecia areata, idiopathic dilated cardiomyopathy, type 1 diabetes mellitus, Graves' disease, Hashimoto's thyroiditis, myasthenia gravis, IgA nephropathy, membranous nephropathy, and pernicious anaemia. It also occurs in healthy blood relatives of patients with autoimmune diseases, suggesting it is genetically determined. Here it is proposed that this CD8+ T-cell deficiency underlies the development of chronic autoimmune diseases by impairing CD8+ T-cell control of Epstein-Barr virus (EBV) infection, with the result that EBV-infected autoreactive B cells accumulate in the target organ where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells which would otherwise die in the target organ by activation-induced apoptosis. Autoimmunity is postulated to evolve in the following steps: (1) CD8+ T-cell deficiency, (2) primary EBV infection, (3) decreased CD8+ T-cell control of EBV, (4) increased EBV load and increased anti EBV antibodies, (5) EBV infection in the target organ, (6) clonal expansion of EBV-infected autoreactive B cells in the target organ, (7) infiltration of autoreactive T cells into the target organ, and (8) development of ectopic lymphoid follicles in the target organ. It is also proposed that deprivation of sunlight and vitamin D at higher latitudes facilitates the development of autoimmune diseases by aggravating the CD8+ T-cell deficiency and thereby further impairing control of EBV. The hypothesis makes predictions which can be tested, including the prevention and successful treatment of chronic autoimmune diseases by controlling EBV infection. PMID- 22312485 TI - Social-cognitive bias and depressive symptoms in outpatients with bipolar disorder. AB - A deficit of social cognition in bipolar disorder has been shown, even when patients are stable. This study compares the attribution of intentions (social cognitive bias) in a group of 37 outpatients with bipolar disorder with 32 matched control subjects. Bipolar patients scored significantly higher in the Ambiguous Intentions Hostility Questionnaire, showing an angry and intentionality bias (P = .001, P = .02). Differences in blame scale and hostility bias did not reach statistical significance, but a trend was found (P = .06). Bipolar patients with depressive symptoms presented a higher score in the angry bias scale (P = .03) and aggressivity bias scale (P = .004). The global functioning (GAF) correlates significantly with intentionality (P = .005), angry (P = .027), and aggressivity (P = .020) biases. Bipolar patients show a social-cognitive bias that may play a role in their functional outcome. PMID- 22312486 TI - Outcome in Advanced Ovarian Cancer following an Appropriate and Comprehensive Effort at Upfront Cytoreduction: A Twenty-Year Experience in a Single Cancer Institute. AB - Objectives. The purpose of this retrospective evaluation of advanced-stage ovarian cancer patients was to compare outcome with published findings from other centers and to discuss future options for the management of advanced ovarian carcinoma patients. Methods. A retrospective series of 340 patients with a mean age of 58 years (range: 17-88) treated for FIGO stage III and IV ovarian cancer between January 1985 and January 2005 was reviewed. All patients had primary cytoreductive surgery, without extensive bowel, peritoneal, or systematic lymph node resection, thereby allowing initiation of chemotherapy without delay. Chemotherapy consisted of cisplatin-based chemotherapy in combination with alkylating agents before 2000, whereas carboplatin and paclitaxel regimes were generally used after 1999-2000. Overall survival and disease-free survival were analyzed by the Kaplan-Meier method and the log-rank test. Results. With a mean followup of 101 months (range: 5 to 203), 280 events (recurrence or death) were observed and 245 patients (72%) had died. The mortality and morbidity related to surgery were low. The main prognostic factor for overall survival was postoperative residual disease (P < .0002), while the main prognostic factor for disease-free survival was histological tumor type (P < .0007). Multivariate analysis identified three significant risk factors: optimal surgery (RR = 2.2 for suboptimal surgery), menopausal status (RR = 1.47 for postmenopausal women), and presence of a taxane in the chemotherapy combination (RR = 0.72). Conclusion. These results confirm that optimal surgery defined by an appropriate and comprehensive effort at upfront cytoreduction limits morbidity related to the surgical procedure and allows initiation of chemotherapy without any negative impact on survival. The impact of neoadjuvant chemotherapy to improve resectability while lowering the morbidity of the surgical procedure is discussed. PMID- 22312487 TI - Transcatheter arterial chemoembolization is a feasible palliative locoregional therapy for breast cancer liver metastases. AB - Background. Liver metastases are common in advanced breast cancer. We sought to evaluate the role of transcatheter arterial chemoembolization (TACE) in breast cancer patients with hepatic metastases. Methods. A retrospective review of ten patients with breast cancer who were treated with TACE for unresectable liver metastases (1998-2008). Results. All patients, median age 46.5, had received prior systemic chemotherapies. Adriamycin was administered for 6, cisplatin/gemcitabine for 2, cisplatin for one and oxaliplatin for one patient. Median number of TACE cycles was 4. Kaplan Meier survival analysis showed an increase in median survival for patients who responded to treatment when compared to those who did not respond (24 vs 7 months, P = .02). Conclusions. This is one of the largest series of breast cancer patients with liver metastases treated with TACE. It suggests that TACE is a feasible palliative option and warrants further investigations. PMID- 22312488 TI - An evaluation of the diagnostic accuracy of the grade of preoperative biopsy compared to surgical excision in chondrosarcoma of the long bones. AB - Chondrosarcoma is the second most common primary malignant bone tumour. Distinguishing between grades is not necessarily straightforward and may alter the disease management. We evaluated the correlation between histological grading of the preoperative image-guided needle biopsy and the resection specimen of 78 consecutive cases of chondrosarcoma of the femur, humerus, and tibia. In 11 instances, there was a discrepancy in histological grade between the biopsy and surgical specimen. Therefore, there was an 85.9% (67/78) accuracy rate for pre operative histological grading of chondrosarcoma, based on needle biopsy. However, the accuracy of the diagnostic biopsy to distinguish low-grade from high grade chondrosarcoma was 93.6% (73/78). We conclude that accurate image-guided biopsy is a very useful adjunct in determining histological grade of chondrosarcoma and the subsequent treatment plan. At present, a multidisciplinary approach, comprising experienced orthopaedic surgeons, radiologists, and pathologists, offers the most reliable means of accurately diagnosing and grading of chondrosarcoma of long bones. PMID- 22312489 TI - Refusal of cancer-directed surgery strongly impairs survival of patients with localized hepatocellular carcinoma. AB - BACKGROUND: This study investigated the frequency of patients with HCC who refused cancer-directed surgery and the characteristics and outcomes of these patients. PATIENTS AND METHODS: A retrospective study was performed using data from the Surveillance, Epidemiology, and End RESULTS (SEER) Program. Characteristics of patients who refused CDS were compared with those who accepted surgery using logistic regression. The effect of refusing CDS on mortality was evaluated by Cox proportional hazards analysis. RESULTS: Among 4373 surgical candidates, 142 patients (3.2%) refused the recommended CDS. The patients who refused CDS were frequently older, African American, widowed or divorced, and had advanced-stage tumors. In a logistic regression analysis, older age, African American, and being divorced or widowed were independently associated with refusal of CDS. After adjusting for other patient and tumor characteristics, the patients who refused CDS had a 2.5-fold (95% confidence interval, 2.339-3.189) higher risk of dying from HCC in comparison with patients who had CDS. CONCLUSIONS: The high rate of refusal may contribute in part to the disparity in utilization of CDS. Of greatest concern is that the patients who declined CDS had an impaired survival. This information might be helpful for patients to make a better-informed decision. PMID- 22312490 TI - Diagnosis and treatment of a neck node swelling suspicious for a malignancy: an algorithmic approach. AB - Aim. To present an up-to-date algorithm incorporating recent advances regarding its diagnosis and treatment. Method. A Medline/Pubmed search was performed to identify relevant studies published in English from 1990 until 2008. Only clinical studies were identified and were used as basis for the diagnostic algorithm. Results. The eligible literature provided only observational evidence. The vast majority of neck nodes from occult primaries (>90%) represent SCC with a high incidence among middle aged man. Smoking and alcohol abuse are important risk factors. Asiatic and North African patients with neck node metastases are at risk of harbouring an occult nasopharyngeal carcinoma. The remainder are adenocarcinoma, undifferentiated carcinoma, melanoma, thyroid carcinoma and Merkel cell carcinoma. Fine needle aspiration cytology (FNAC) reaches sensitivity and specificity percentages of 81% and 100%, respectively and plays an important role as the second diagnostic step after routine ENT mirror and/or endoscopic examination. FDG-PET/CT has proven to be helpful in identifying occult primary carcinomas of the head and neck, especially when applied as a guiding tool prior to panendoscopy, and may induce treatment related clinical decisions in up to 60% of cases. Conclusion. Although reports on the diagnostic process offer mainly descriptive studies, current information seems sufficient to formulate a diagnostic algorithm to contribute to a more systematic diagnostic approach preventing unnecessary steps. PMID- 22312491 TI - Physiopathology of spine metastasis. AB - The metastasis is the spread of cancer from one part of the body to another. Two thirds of patients with cancer will develop bone metastasis. Breast, prostate and lung cancer are responsible for more than 80% of cases of metastatic bone disease. The spine is the most common site of bone metastasis. A spinal metastasis may cause pain, instability and neurological injuries. The diffusion through Batson venous system is the principal process of spinal metastasis, but the dissemination is possible also through arterial and lymphatic system or by contiguity. Once cancer cells have invaded the bone, they produce growth factors that stimulate osteoblastic or osteolytic activity resulting in bone remodeling with release of other growth factors that lead to a vicious cycle of bone destruction and growth of local tumour. PMID- 22312492 TI - Psychological problems derived from mastectomy: a qualitative study. AB - Advances in treatment of breast cancer have not avoided using mastectomy in all cases, and when this happens, we are dealing with a woman who is suffering from psychological problems. In order to study this issue we have carried out a research with the collaboration of The Andalusian Association of Women with Mastectomies (AMAMA) in Seville, which provided us with a sample of 46 mastectomized women. The objective of this study is to analyze in depth the psychological reaction of women to mastectomy through its different stages from diagnosis to surgical treatment. We chose a cualitative method so as to explore the subjective components of psicologycal respons. As a result, we found in studied women: (a) The "fracture" of the "corporal imaginary" related to the disappearance of a valuable organ, linked to the feeling of loss of personal attractiveness, low self-esteem and avoidance of social relationships. (b) The problem with "femininity" has been linked to the issue of "desirability", something innate in the "feminine position". (c) Many of them keep in mind the idea of mutilation, as a "hole" which is impossible to integrate. (d) Finally, we demonstrate how certain features of personality made them especially vulnerable to the explained phenomena. PMID- 22312494 TI - Intraperitoneal gemcitabine chemotherapy treatment for patients with resected pancreatic cancer: rationale and report of early data. AB - Currently, the surgical management of pancreas cancer is recognized around the world as inadequate. Despite a potentially curative R0 resection, long-term survival is rare. There is a strong rationale for the use of chemotherapy in the operating room to reduce local-regional of recurrent/progressive disease. Gemcitabine monotherapy administered by an intraperitoneal route in the operating room with hyperthermia and then for long-term treatment postoperatively has a pharmacologic basis in that the exposure of peritoneal surfaces to intraperitoneal gemcitabine is approximately 200-500 times the exposure that occurs within the plasma. A standardized treatment with intraoperative and long term chemotherapy that is well tolerated would greatly facilitate further improvements in pancreas cancer treatment and may lead the way to an evolution of more successful treatment strategies of this dread disease. The aim of this paper is to present the early data on a protocol in progress in patients with resected pancreatic cancer. PMID- 22312493 TI - Hereditary pancreatic and hepatobiliary cancers. AB - Hereditary etiologies of pancreatic and hepatobiliary cancers are increasingly recognized. An estimated >10% of pancreatic and increasing number of hepatobiliary cancers are hereditary. The cumulative risk of hereditary pancreatic cancer ranges from measurable but negligible in cystic fibrosis to a sobering 70% in cases of hereditary pancreatitis. Candidates for pancreatic cancer surveillance are those with a risk pancreatic cancer estimated to be >10 fold that of the normal population. Screening for pancreatic cancer in high-risk individuals is typically performed by endoscopic ultrasound and should begin at least 10 years prior to the age of the youngest affected relative. Disease states known to be associated with increased risk of hepatocellular cancer include hereditary hemochromatosis, autoimmune hepatitis, porphyria, and alpha1 antitrypsin deficiency, with relative risks as high as 36-fold. Although much less is known about hereditary bile-duct cancers, Muir-Torre syndrome and bile salt export pump deficiency are diseases whose association with hereditary carcinogenesis is under investigation. PMID- 22312495 TI - Intraosseous synovial sarcoma of the proximal tibia. AB - Synovial Sarcoma is a malignant mesenchymal tumor that comprises 5-10% of all soft tissue sarcomas. The mean age of onset is thirty years old. Intraosseous presentation is very rare and has only been documented a few times. We report herein a case of a 53-year-old man with synovial sarcoma arising in the left proximal tibia. The patient underwent a wide surgical resection and reconstruction, followed by adjuvant chemotherapy. Three years later, the patient developed a local recurrence that resulted in an above-the-knee amputation. Eight months later, the patient has completed chemotherapy and is without signs of recurrence. The current recommended treatment for synovial sarcoma is wide surgical resection followed by chemotherapy as well as long-term followup. Despite improved surgical techniques, long-term survival rates remain low. PMID- 22312496 TI - Pharmacokinetic study of perioperative intravenous Ifosfamide. AB - The use of cancer chemotherapy and hyperthermia as part of a surgical procedure in the management of patients with peritoneal carcinomatosis has gained prominence in recent years with selected patients showing benefit. Patients with peritoneal surface malignancy following cancer resection were treated with intraperitoneal hyperthermic (41.5-42.5 degrees C) cisplatin and doxorubicin combined with the infusion of systemic ifosfamide chemotherapy. The concentrations of ifosfamide and 4-hydroxyifosfamide were determined in plasma, peritoneal fluid, urine, and when possible, within small tumor nodules less than 1 cm. Plasma concentrations of ifosfamide exceeded peritoneal fluid levels of ifosfamide during the 90 minutes of chemotherapy infusion. Both ifosfamide and 4 hydroxyifosfamide could be recovered from peritoneal tumor nodules throughout the 90 minutes of ifosfamide continuous infusion and exceeded plasma concentrations. 4-Hydroxyifosfamide within peritoneal surface cancer nodules suggested a favorable pharmacologic endpoint in the study of ifosfamide administered in the operating room. PMID- 22312497 TI - Molecular markers in cutaneous squamous cell carcinoma. AB - Nonmelanoma skin carcinoma (NMSC) is the most frequent cancer in the USA with over 1.3 million new diagnoses a year; however due to an underappreciation of its associated mortality and growing incidence and its ability to be highly aggressive, the molecular mechanism is not well delineated. Whereas the molecular profiles of melanoma have been well characterized, those for cutaneous squamous cell carcinoma (cSCC) have trailed behind. This importance of the new staging paradigm is linked to the ability currently to better clinically cluster similar biologic behavior in order to risk-stratify lesions and patients. In this paper we discuss the trends in NMSC and the etiologies for the subset of NMSC with the most mortality, cutaneous SCC, as well as where the field stands in the discovery of a molecular profile. The molecular markers are highlighted to demonstrate the recent advances in cSCC. PMID- 22312498 TI - Minimally Invasive Posterior Stabilization Improved Ambulation and Pain Scores in Patients with Plasmacytomas and/or Metastases of the Spine. AB - Background. The incidence of spine metastasis is expected to increase as the population ages, and so is the number of palliative spinal procedures. Minimally invasive procedures are attractive options in that they offer the theoretical advantage of less morbidity. Purpose. The purpose of our study was to evaluate whether minimally invasive posterior spinal instrumentation provided significant pain relief and improved function. Study Design. We compared pre- and postoperative pain scores as well as ambulatory status in a population of patients suffering from oncologic conditions in the spine. Patient Sample. A consecutive series of patients with spine tumors treated minimally invasively with stabilization were reviewed. Outcome Measures. Visual analog pain scale as well as pre- and postoperative ambulatory status were used as outcome measures. Methods. Twenty-four patients who underwent minimally invasive posterior spinal instrumentation for metastasis were retrospectively reviewed. Results. Seven (29%) patients were unable to ambulate secondary to pain and instability prior to surgery. All patients were ambulating within 2 to 3 days after having surgery (P = 0.01). The mean visual analog scale value for the preoperative patients was 2.8, and the mean postoperative value was 1.0 (P = 0.001). Conclusion. Minimally invasive posterior spinal instrumentation significantly improved pain and ambulatory status in this series. PMID- 22312499 TI - Imaging by Magnifying Endoscopy with NBI Implicates the Remnant Capillary Network As an Indication for Endoscopic Resection in Early Colon Cancer. AB - Introduction. This study examined whether magnifying endoscopy with NBI observation (ME-NBI) could be useful selecting the appropriate treatment for submucosal invasive cancer (SM cancer). Patients and Methods. We analyzed 515 cases of colon tumors excised endoscopically or surgically. We classified capillary network pattern into four types according to the degree of dilatation, irregularity, and distribution of microcapillary features. Results. The comparison of capillary pattern and histological features revealed microcapillary networks by using confocal laser-scanning microscopy and ME-NBI in intramucosal lesion or SM cancer with remnant neoplastic glands at the superficial layer. In contrast, the network was absent in SM cancer with desmoplastic reactions, which invaded deeper into the submucosal layer. Conclusions. The remaining microcapillary network is designed to maintain the architecture of neoplastic glands. Consequently, loss of this network could correlate with depth of tumor invasion and desmoplastic reaction. Therefore, we can decide the appropriate treatment by using ME-NBI method. PMID- 22312500 TI - Selective inguinal lymphadenectomy in the treatment of invasive squamous cell carcinoma of the vulva. AB - En bloc radical vulvectomy with bilateral inguinofemoral lymphadenectomy has now been replaced by radical wide excision and selective inguinal lymphadenectomy based on the stage and location of invasive vulvar cancer. Early stage lateral cancers can be effectively treated by radical wide excision and ipsilateral superficial inguinal lymphadenectomy. Lymph node mapping using perilesional injection of radiocolloid and blue dye may identify sentinel lymph nodes which can be removed, thereby avoiding the morbidity of full inguinal lymphadenectomy in selected patients with early stage disease. PMID- 22312501 TI - Colorectal liver metastases. AB - The diagnosis and management of CRLM is complex and requires a multidisciplinary team approach for optimal outcomes. Over the past several decades, the 5-year survival following resection of CRLM has increased and the criteria for resection have broadened substantially. Even patients with multiple, bilateral CRLM, previously thought unresectable, may now be candidates for resection. Two-stage hepatectomy, repeat curative-intent hepatectomy, and even selected resection of extrahepatic metastases have further increased the number of patients who may be treated with curative intent. Multiple liver-directed therapies exist to treat unresectable, incurable patients with adequate survival benefit and morbidity rates. PMID- 22312503 TI - Spine metastasis. PMID- 22312502 TI - Clinical Considerations of BRCA1- and BRCA2-Mutation Carriers: A Review. AB - Individuals who carry an inherited mutation in the breast cancer 1 (BRCA1) and BRCA2 genes have a significant risk of developing breast and ovarian cancer over the course of their lifetime. As a result, there are important considerations for the clinician in the counseling, followup and management of mutation carriers. This review outlines salient aspects in the approach to patients at high risk of developing breast and ovarian cancer, including criteria for genetic testing, screening guidelines, surgical prophylaxis, and chemoprevention. PMID- 22312504 TI - Technical advances in skin sparing mastectomy. AB - Skin sparing mastectomy has resulted in marked improvement in the aesthetic results of immediate breast reconstruction. Mature data has confirmed its oncological safety in the treatment of breast cancer. The procedure has gained wide acceptance and has undergone numerous technical advances since its introduction over twenty years ago. Careful patient selection and choice of skin incisions are necessary to avoid complications. PMID- 22312505 TI - Same Surgeon: Different Centre Equals Differing Lymph Node Harvest following Colorectal Cancer Resection. AB - Introduction. The aim of this study was to examine the effect of surgeon relocation on lymph node (LN) retrieval in colorectal cancer (CRC) resection. Methods. The study population was 213 consecutive patients undergoing CRC resection by a single surgeon, at two units: unit one 110 operations (2002-2005) and unit two 103 (2005-2009). LN yields and case mix were compared. Results. Median LN harvests were significantly different between the two centres: unit 1: 13 nodes/patient and unit 2: 22 nodes/patient (P < .001). In unit one 42% of cases were LN positive and in unit two 48% (P = .398). There was no difference in case mix. Multivariate analysis identified unit (P < .001) and pathologist (P = .007) as independent predictors of harvest. Conclusions. A surgeon moving units can experience significantly different LN yield following CRC resection. Both units comply with national standards, but the "surgeon's results" at the two units appear to be pathologist dependent. This has implications for nodal harvest as a surrogate marker of surgical quality. PMID- 22312506 TI - Microsurgical reconstruction of large, locally advanced cutaneous malignancy of the head and neck. AB - Large, locally advanced cutaneous malignancy of the head and neck region is rare. However, when present, they impart a significant reconstructive challenge. These cancers have a tendency to invade peripheral tissues covering a large surface area as well as expose deeper structures such as skull, dura, orbit, and sinus after resection. Complicating the reconstructive dilemma is the high incidence of individuals who have undergone previous surgery in the region as well as adjuvant radiation therapy, which may preclude the use of local flaps or skin graft. Free tissue transfer provides a reconstructive surgeon the ability to provide well vascularized tissue with adequate volume not limited by arc of rotation. PMID- 22312507 TI - Effect of Magnetic Resonance Imaging on Breast Conservation Therapy versus Mastectomy: A Review of the Literature. AB - The utilization of MRI in the workup of breast cancer has played a controversial role in the surgical treatment of this disease. With the higher resolution of breast tissue afforded, additional lesions are being identified that often warrant additional procedures, subsequently affecting the decision to proceed with breast conservation therapy versus mastectomy. In this paper, a literature review is presented to help illuminate some of the benefits and pitfalls of employing MRI as a diagnostic tool in the care of breast cancer, while additionally providing insight into the management alterations this imaging modality can engender. Though further research is required in a randomized prospective form to fully answer this question, evidence for and against its use continues to mount, especially for select patient groups. PMID- 22312508 TI - Concomitant radiotherapy and chemotherapy for high-risk nonmelanoma skin carcinomas of the head and neck. AB - Background. To report on the use and feasibility of a multimodality approach using concomitant radiotherapy and chemotherapy in patients with high-risk nonmelanoma skin carcinoma (NMSC) of the head and neck. Methods. Records of patients with NMSC of the head and neck who received concomitant CRT at the University of North Carolina between 2001 and 2007 were reviewed. Results. Fifteen identified patients had at least one of the following high-risk factors: T4 disease (93%), unresectability (60%), regional nodal involvement (40%), and/or recurrence (47%). Ten patients were treated in the definitive setting and five in the postoperative setting. Platinum based chemotherapy was given in 14 (93%) patients. Ten of fifteen (67%) patients completed all planned chemotherapy treatments, and thirteen patients (87%) completed at least 80% of planned chemotherapy. Mild radiation dermatitis occurred in all patients and reached grade 3 in 13% of patients. No patients experienced grade 4 or 5 toxicity. With a median followup of 31 months in surviving patients, the 2-year actuarial locoregional control and relapse-free survival were 79% and 49%, respectively. Conclusions. Definitive or postoperative chemoradiotherapy for patients with locally advanced or regionally metastasized NMSC of the head and neck appears feasible with acceptable toxicities and favorable locoregional control. PMID- 22312509 TI - Gastrointestinal complications in 147 consecutive patients with peritoneal surface malignancy treated by cytoreductive surgery and perioperative intraperitoneal chemotherapy. AB - Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly used in the treatment of peritoneal carcinomatosis from gastrointestinal malignancies. The purpose of this study is to reevaluate the incidence of gastrointestinal events and identify risk factors associated with this treatment approach. Between January 1, 2006 and December 31, 2009, 147 patients with appendiceal and colorectal carcinomatosis were treated. Gastrointestinal events were analyzed. The overall incidence of grade I-IV gastrointestinal events was 17%. There were 4 grade III gastrointestinal events that occurred in 4 patients and 11 grade IV gastrointestinal events that occurred in 8 patients. On univariate analysis of grade I-IV events a statistically significant association was observed with the following variables: histological grade, peritoneal cancer index (PCI), small bowel resection, colorectal anastomosis, and the number of anastomoses performed per patient. By multivariate analysis, PCI was identified as the only independent risk factor for gastrointestinal complications. CRS combined with a uniform HIPEC regimen is associated with a 17% gastrointestinal morbidity rate (grade I-IV). The frequency of gastrointestinal complications was associated with a large extent of disease measured by PCI (>30). PMID- 22312510 TI - A Single Centre Retrospective Evaluation of Laparoscopic Rectal Resection with TME for Rectal Cancer: 5-Year Cancer-Specific Survival. AB - Laparoscopic colon resection has established its role as a minimally invasive approach to colorectal diseases. Better long-term survival rate is suggested to be achievable with this approach in colon cancer patients, whereas some doubts were raised about its safety in rectal cancer. Here we report on our single centre experience of rectal laparoscopic resections for cancer focusing on short- and long-term oncological outcomes. In the last 13 years, 248 patients underwent minimally invasive approach for rectal cancer at our centre. We focused on 99 stage I, II, and III patients with a minimum follow-up period of 5 years. Of them 43 had a middle and 56 lower rectal tumor. Laparoscopic anterior rectal resection was performed in 71 patients whereas laparoscopic abdomino-perineal resection in 28. The overall mortality rate was 1%; the overall morbidity rate was 29%. The 5 year disease-free survival rate was 69.7%, The 5-year overall survival rate was 78.8%. PMID- 22312512 TI - Minimally invasive treatment of spinal metastases: techniques. AB - With improved treatments and increasingly life expectancy, the burden of metastatic disease in the spine is expected to rise. The role of conventional surgery for spinal metastases is well established but often involves procedures of large magnitude. We describe minimally invasive techniques for spinal stabilization and decompression in patients with symptomatic metastatic disease of the spine. PMID- 22312511 TI - Minimally invasive surgery for colorectal cancer: past, present, and future. AB - A rapid progression from conventional open surgery to minimally invasive approaches in the surgical management of colorectal cancer has occurred over the last 2 decades. Initial concerns that this new approach was oncologically inferior to open surgery were ultimately refuted when several prospective randomized trials concluded that laparoscopic colectomy could achieve similar oncologic outcomes to open surgery. On the contrary, level 1 data has not yet matured regarding the oncologic safety of minimally invasive approaches for rectal cancer. We review the published literature pertaining to the evolution of minimally invasive techniques used to treat colorectal cancer surgery, including barriers to adoption, and the prospects for future advances related to innovative techniques. PMID- 22312513 TI - Yttrium-90 radioembolization for colorectal cancer liver metastases: a single institution experience. AB - Purpose. We sought to evaluate our experience using yttrium-90 ((90)Y) resin microsphere hepatic radioembolization as salvage therapy for liver-dominant metastatic colorectal cancer (mCRC). Methods. A retrospective review of consecutive patients with unresectable mCRC who were treated with (90)Y after failing first and second line systemic chemotherapy. Demographics, treatment dose, biochemical and radiographic response, toxicities, and survival were examined. Results. Fifty-one patients underwent (90)Y treatments of which 69% were male. All patients had previously undergone extensive chemotherapy, 31% had undergone previous liver-directed therapy and 24% had a prior liver resection. Using RECIST criteria, either stable disease or a partial response was seen in 77% of patients. Overall median survival from the time of first (90)Y treatment was 10.2 months (95% CI = 7.5-13.0). The absence of extrahepatic disease at the time of treatment with (90)Y was associated with an improved survival, median survival of 17.0 months (95% CI = 6.4-27.6), compared to those with extrahepatic disease at the time of treatment with (90)Y, 6.7 months (95% CI = 2.7-10.6 CONCLUSION: (90)Y therapy is a safe locoregional therapy that provides an important therapeutic option to patients who have failed first and second line chemotherapy and have adequate liver function and performance status. PMID- 22312514 TI - A systematic review of the current role of minimally invasive spine surgery in the management of metastatic spine disease. AB - Although increasingly aggressive decompression and resection methods have resulted in improved outcomes for patients with metastatic spine disease, these aggressive surgeries are not feasible for patients with numerous comorbid conditions. Such patients stand to benefit from management via minimally invasive spine surgery (MIS), given its association with decreased perioperative morbidity. We performed a systematic review of literature with the goal of evaluating the clinical efficacy and safety of MIS in the setting of metastatic spine disease. Results suggest that MIS is an efficacious means of achieving neurological improvement and alleviating pain. In addition, data suggests that MIS offers decreased blood loss, operative time, and complication rates in comparison to standard open spine surgery. However, due to the paucity of studies and low class of available evidence, the ability to draw comprehensive conclusions is limited. Future investigations should be conducted comparing standard surgery versus MIS in a prospective fashion. PMID- 22312515 TI - Hyperplastic polyps are innocuous lesions in hereditary nonpolyposis colorectal cancers. AB - Aims. To compare methylation profiles, protein expression, and microsatellite instability (MSI) of sporadic, HNPCC, and familial hyperplastic polyps (HPs). Methods. Methylation-specific PCR (MSP) and pyrosequencing assessed p16, MGMT, hMLH-1, MINT 1, and MINT 31 methylation. IHC (Immunohistochemistry) assessed Ki67, CK20, hMLH-1, hMSH-2, and hMSH-6 protein expression. MSI analysis was performed on those polyps with adequate DNA remaining. Results. 124 HPs were identified 78 sporadic, 21 HNPCC, 25 familial, and the HNPCC group demonstrated no significant differences in overall methylation (P = .186 Chi(2)). The familial group demonstrated significantly less over all methylation levels (P = .004 Chi(2)). Conclusions. HPs that occur in HNPCC have no more worrying features at a molecular level than those patients with HPs in a sporadic setting. PMID- 22312516 TI - Familial renal cancer: molecular genetics and surgical management. AB - Familial renal cancer (FRC) is a heterogeneous disorder comprised of a variety of subtypes. Each subtype is known to have unique histologic features, genetic alterations, and response to therapy. Through the study of families affected by hereditary forms of kidney cancer, insights into the genetic basis of this disease have been identified. This has resulted in the elucidation of a number of kidney cancer gene pathways. Study of these pathways has led to the development of novel targeted molecular treatments for patients affected by systemic disease. As a result, the treatments for families affected by von Hippel-Lindau (VHL), hereditary papillary renal carcinoma (HPRC), hereditary leiomyomatosis renal cell carcinoma (HLRCC), and Birt-Hogg-Dube (BHD) are rapidly changing. We review the genetics and contemporary surgical management of familial forms of kidney cancer. PMID- 22312517 TI - Selection criteria for the radical treatment of locally advanced rectal cancer. AB - There are over 14,000 newly diagnosed rectal cancers per year in the United Kingdom of which between 50 and 64 percent are locally advanced (T(3)/T(4)) at presentation. Pelvic exenterative surgery was first described by Brunschwig in 1948 for advanced cervical cancer, but early series reported high morbidity and mortality. This approach was later applied to advanced primary rectal carcinomas with contemporary series reporting 5-year survival rates between 32 and 66 percent and to recurrent rectal carcinoma with survival rates of 22-42%. The Swansea Pelvic Oncology Group was established in 1999 and is involved in the assessment and management of advanced pelvic malignancies referred both regionally and UK wide. This paper will set out the selection, assessment, preparation, surgery, and outcomes from pelvic exenterative surgery for locally advanced primary rectal carcinomas. PMID- 22312519 TI - A new laparoscopic surgical procedure to achieve sufficient mesorectal excision in upper rectal cancer. AB - Objective. Mesorectal excision corresponding to the location of a tumor, termed tumor-specific mesorectal excision (TSME), is commonly performed for resection of upper rectal cancer. We devised a new laparoscopic procedure for sufficient TSME with rectal transection followed by mesorectal excision. Operative Technique. After mobilization of the sigmoid colon and ligation of inferior mesenteric vessels, we dissected the mesorectum along the layer of the planned total mesorectal excision. The rectal wall was carefully separated from the mesorectum at the appropriate anal side from the tumor. After the rectum was isolated and transected using an endoscopic linear stapler, the rectal stump drew immediately toward the anal side, enabling the mesorectum to be identified clearly. In this way, sufficient TSME can be performed easily and accurately. This technique has been successfully conducted on 19 patients. Conclusion. This laparoscopic technique is a feasible and reliable procedure for achieving sufficient TSME. PMID- 22312518 TI - Minimally invasive evaluation and treatment of colorectal liver metastases. AB - Minimally invasive techniques used in the evaluation and treatment of colorectal liver metastases (CRLMs) include ultrasonography (US), computed tomography, magnetic resonance imaging, percutaneous and operative ablation therapy, standard laparoscopic techniques, robotic techniques, and experimental techniques of natural orifice endoscopic surgery. Laparoscopic techniques range from simple staging laparoscopy with or without laparoscopic intraoperative US, through intermediate techniques including simple liver resections (LRs), to advanced techniques such as major hepatectomies. Hereins, we review minimally invasive evaluation and treatment of CRLM, focusing on a comparison of open LR (OLR) and minimally invasive LR (MILR). Although there are no randomized trials comparing OLR and MILR, nonrandomized data suggest that MILR compares favorably with OLR regarding morbidity, mortality, LOS, and cost, although significant selection bias exists. The future of MILR will likely include expanding criteria for resectability of CRLM and should include both a patient registry and a formalized process for surgeon training and credentialing. PMID- 22312520 TI - A New Candidate Supporting Drug, Rikkunshito, for the QOL in Advanced Esophageal Cancer Patients with Chemotherapy Using Docetaxel/5-FU/CDDP. AB - Purpose. Docetaxel/5-FU/CDDP (DFP) therapy is a useful treatment for advanced esophageal cancer. However, adverse reactions such as chemotherapy-induced nausea and vomiting (CINV) interfere often with continuation of the chemotherapy. We investigated the efficacy of rikkunshito (TJ-43) on CINV. Methods. Nineteen patients who were going to undergo DFP therapy were enrolled. They were assigned to the following two groups: a TJ-43-treated group and -nontreated group. The following parameters were compared between the 2 groups: (1) the frequency of symptoms occurred, (2) vomiting, nausea, and anorexia score, and (3) QOL score. Results. The incidence of symptoms was lower in the TJ-43-treated group than that in the control group. The nausea score of the TJ-43-treated group was significantly lower than that of the control group. In the QOL score, the mood score and the ADL score decreased significantly in the control group. Conclusion. We recommend TJ-43 administration in patients undergoing DFP chemotherapy. PMID- 22312521 TI - Lymph node dissection in curative gastrectomy for advanced gastric cancer. AB - Gastric cancer is one of the most common causes of cancer-related death worldwide. Surgical resection with lymph node dissection is the only potentially curative therapy for gastric cancer. However, the appropriate extent of lymph node dissection accompanied by gastrectomy for cancer remains controversial. In East Asian countries, especially in Japan and Korea, D2 lymph node dissection has been regularly performed as a standard procedure. In Western countries, surgeons perform gastrectomy with D1 dissection only because D2 is associated with high mortality and morbidity compared to those associated with D1 alone but does not improve the 5-year survival rate. However, more recent studies have demonstrated that western surgeons can be trained to perform D2 lymphadenectomies on western patients with a lower morbidity and mortality. When extensive D2 lymph node dissection is preformed safely, there may be some benefit to D2 dissection even in western countries. In this paper, we present an update on the current literature regarding the extent of lymphadenectomy for advanced gastric cancer. PMID- 22312522 TI - Lymphadenectomy in management of invasive bladder cancer. AB - Radical cystectomy with pelvic lymphadenectomy represents the gold standard for treatment of muscle-invasive bladder cancer. Extent of the lymph node dissection and lymph node involvement during radical cystectomy are the most powerful prognostic factors associated with poor oncological outcome. However, the optimal boundaries of the lymph node dissection during a radical cystectomy are controversial. The published literature based mostly on retrospective studies suggests that increasing the number of nodes excised may have therapeutic and diagnostic benefits without significantly increasing the surgical morbidity. These conclusions are, however, influenced by selection and surgeon biases, inconsistencies in the quality of the surgery, and node count variability. In this paper, we establish the current understanding about the utility of lymphadenectomy during a radical cystectomy for muscle-invasive bladder cancer. PMID- 22312523 TI - Imaging of spinal metastatic disease. AB - Metastases to the spine can involve the bone, epidural space, leptomeninges, and spinal cord. The spine is the third most common site for metastatic disease, following the lung and the liver. Approximately 60-70% of patients with systemic cancer will have spinal metastasis. Materials/Methods. This is a review of the imaging techniques and typical imaging appearances of spinal metastatic disease. Conclusions. Awareness of the different manifestations of spinal metastatic disease is essential as the spine is the most common site of osseous metastatic disease. Imaging modalities have complimentary roles in the evaluation of spinal metastatic disease. CT best delineates osseous integrity, while MRI is better at assessing soft tissue involvement. Physiologic properties, particularly in treated disease, can be evaluated with other imaging modalities such as FDG PET and advanced MRI sequences. Imaging plays a fundamental role in not only diagnosis but also treatment planning of spinal metastatic disease. PMID- 22312524 TI - Higher Volume at Time of Breast Conserving Surgery Reduces Re-Excision in DCIS. AB - Purpose. The purpose of this study was to compare the surgical and pathological variables which impact rate of re-excision following breast conserving therapy (BCS) with or without concurrent additional margin excision (AM). Methods. The pathology database was queried for all patients with DCIS from January 2004 to September 2008. Pathologic assessment included volume of excision, subtype, size, distance from margin, grade, necrosis, multifocality, calcifications, and ER/PR status. Results. 405 cases were identified and 201 underwent BCS, 151-BCS-AM, and 53-mastectomy. Among the 201 BCS patients, 190 underwent re-excision for close or involved margins. 129 of these were treated with BCS and 61 with BCS-AM (P < .0001). The incidence of residual DCIS in the re-excision specimens was 32% (n = 65) for BCS and 22% (n = 33) for BCS-AM (P < .05). For both the BCS and the BCS AM cohorts, volume of tissue excised is inversely correlated to the rate of re excision (P = .0284). Multifocality (P = .0002) and ER status (P = .0382) were also significant predictors for rate of re-excision and variation in surgical technique was insignificant. Conclusions. The rate of positive margins, re excision, and residual disease was significantly higher in patients with lower volume of excision. The performance of concurrent additional margin excision increases the efficacy of BCS for DCIS. PMID- 22312525 TI - The role of lymphadenectomy in surgical staging of endometrial cancer. AB - Surgical staging, including lymph node sampling, for endometrial cancer was adopted by the International Federation of Gynecology and Obstetrics (FIGO) in 1988 based on reports demonstrating diagnostic and therapeutic advantages. This review focuses on the incidence of lymph node metastasis, risk factors for lymph node involvement, the effect of lymph node metastasis on prognosis, the therapeutic effect and diagnostic usefulness of lymphadenectomy, risks of lymph node dissection, and future directions in surgical staging of endometrial cancer. Surgical staging identifies most patients with extrauterine disease as well as uterine risk factors for recurrence, thereby allowing for a more informed approach to postoperative adjuvant therapy. Lymphadenectomy as a part of surgical staging is not required in patients assessed intraoperatively to be at low risk for lymph node metastasis (<2 cm grade 1 tumors with superficial myometrial invasion), however, a systematic lymph node dissection should be performed in most other patients with endometrial cancer. In the future, molecular markers may be useful to predict preoperatively tumor aggressiveness and lymph node metastasis. It is hoped that an approach of surgical staging with selective lymph node dissection will improve survival and spare patients additional surgical complications or unnecessary postoperative exposure to radiation and/or chemotherapy. PMID- 22312526 TI - The current role of lymph node dissection in the management of renal cell carcinoma. AB - The role of lymph node dissection remains controversial in the surgical management of renal cell carcinoma. Incidental renal masses are being diagnosed at increasing rates due to the routine use of CT scans. Despite the increase in incidental diagnosis of renal masses, 20% to 30% of patients present with metastatic disease. Currently, surgeons do not routinely perform lymph node dissection unless there is gross evidence of lymphadenopathy, as patients without clinical evidence of lymphadenopathy rarely have positive nodes at the time of surgery. Patients with metastatic disease to the regional lymph nodes have a poor overall prognosis. However, some evidence supports a therapeutic benefit of lymphadenectomy in these patients. Further, the staging information gained from diagnosing lymph node involvement may allow for the use of new agents to treat metastatic disease and effect outcomes. PMID- 22312528 TI - Retrospective comparison of non-skin-sparing mastectomy and skin-sparing mastectomy with immediate breast reconstruction. AB - Background. We compared Skin-sparing mastectomy (SSM) with immediate breast reconstruction and Non-skin-sparing mastectomy (NSSM), various types of incision in SSM. Method. Records of 202 consecutive breast cancer patients were reviewed retrospectively. Also in the SSM, three types of skin incision were used. Type A was a periareolar incision with a lateral extension, type B was a periareolar incision and axillary incision, and type C included straight incisions, a small elliptical incision (base line of nipple) within areolar complex and axillary incision. Results. Seventy-three SSMs and 129 NSSMs were performed. The mean follow-up was 30.0 (SSM) and 41.1 (NSSM) months. Respective values for the two groups were: mean age 47.0 and 57; seven-year cumulative local disease-free survival 92.1% and 95.2%; post operative skin necrosis 4.1% and 3.1%. In the SSM, average areolar diameter in type A & B was 35.4 mm, 43.0 mm in type C and postoperative nipple-areolar plasty was performed 61% in type A & B, 17% in type C, respectively. Conclusion. SSM for early breast cancer is associated with low morbidity and oncological safety that are as good as those of NSSM. Also in SSM, Type C is far superior as regards cost and cosmetic outcomes. PMID- 22312527 TI - The Use of PET-CT in the Assessment of Patients with Colorectal Carcinoma. AB - Colorectal cancer is the third most commonly diagnosed cancer, accounting for 53,219 deaths in 2007 and an estimated 146,970 new cases in the USA during 2009. The combination of FDG PET and CT has proven to be of great benefit for the assessment of colorectal cancer. This is most evident in the detection of occult metastases, particularly intra- or extrahepatic sites of disease, that would preclude a curative procedure or in the detection of local recurrence. FDG PET is generally not used for the diagnosis of colorectal cancer although there are circumstances where PET-CT may make the initial diagnosis, particularly with its more widespread use. In addition, precancerous adenomatous polyps can also be detected incidentally on whole-body images performed for other indications; sensitivity increases with increasing polyp size. False-negative FDG PET findings have been reported with mucinous adenocarcinoma, and false-positive findings have been reported due to inflammatory conditions such as diverticulitis, colitis, and postoperative scarring. Therefore, detailed evaluation of the CT component of a PET/CT exam, including assessment of the entire colon, is essential. PMID- 22312529 TI - Clinical outcome of laparoscopic intersphincteric resection combined with transanal rectal dissection for t3 low rectal cancer in patients with a narrow pelvis. AB - Purpose. The purpose of this study was to analyze the safety and feasibility of laparoscopic intersphincteric resection (ISR) combined with transanal rectal dissection (TARD) for T3 low rectal cancer in a narrow pelvis. Methods. We studied 20 patients with a narrow pelvis of median body mass index 25.3 (16.9 31.2). Median observation period was 23.6 months (range 12.2-56.7). Results. Partial, subtotal, and total ISR was performed in 15, 1, and 4 patients, respectively. Median duration of TARD was 83 min (range 43-135). There were no major complications perioperatively or postoperatively. Surgical margins were histologically free of tumor cells in all patients, and there was no local recurrence. Excluding urgency, frequency of bowel movements, and incontinence status improved gradually after stoma closure. Conclusion. Laparoscopic ISR combined with TARD is technically feasible for selective T3 low rectal cancer in patients with a narrow pelvis. PMID- 22312530 TI - Second-look surgery for colorectal cancer: revised selection factors and new treatment options for greater success. AB - Proper indications for second-look surgery in patients with colorectal cancer have always been a controversial subject. The surgical literature suggests benefit in a reoperation, where a limited extent of cancer is discovered and then resected with negative margins. However, patients are often subjected to a negative exploratory laparotomy or an intervention that is unable to achieve an R 0 resection; in these circumstances, little or no benefit occurs. Unfortunately, an unsuccessful repeat intervention may place the patient in a worse condition, especially if morbidity occurs. This paper seeks to identify the clinical parameters of a primary colorectal cancer and a followup plan that are associated with cancer recurrence that can be definitively addressed by the second look surgery. New surgical technologies, including cytoreductive surgery with peritonectomy and perioperative intraperitoneal chemotherapy with hyperthermia, are suggested for use in this group of patients. This new management strategy used in patients with local-regional recurrence may result in a high proportion of patients converted from a second-look positive patient to a long-term survivor. PMID- 22312531 TI - Colorectal stenting in malignant large bowel obstruction: the learning curve. AB - Aim. Self-expanding metal stents (SEMSs) are increasingly used for the palliation of metastatic colorectal cancer and as a bridge to surgery for obstructing tumours. This case series analyses the learning curve and changes in practice of colorectal stenting over a three year period. Methods. A study of 40 patients who underwent placement of SEMS for the management of colorectal cancer. Patients spanned the learning curve of a single surgeon endoscopist. Results. Technical success rates increased from 82% initially, using an average of 1.7 stents per procedure, to a 94% success rate where all patients were stented using a single stent. There has been a change in practice from elective palliative stenting toward emergency preoperative stenting. Conclusion. There is a steep learning curve for the use of SEMS in the management of malignant colorectal bowel obstruction. We suggest that at least 20 cases are required for an operator to be considered experienced. PMID- 22312532 TI - Treatment of pancreatic and periampullary cancers at a community hospital: successful application of tertiary care treatment standards. AB - Background. The treatment of pancreatic cancer and other periampullary neoplasms is complex and challenging. Major high-volume cancer centers can provide excellent multidisciplinary care of these patients but almost two-thirds of pancreatic cancer patients are treated at low volume centers. There is very little published data from low volume community cancer programs in regards to the treatment of periampullary cancer. In this study, a review of comprehensive periampullary cancer care at two low volume hospitals with comparison to national standards is presented. Methods. This is a retrospective review of 70 consecutive patients with periampullary neoplasms who underwent surgery over a 5-year period (2006-2010) at two community hospitals. Results. There were 51 successful resections of 70 explorations (73%) including 34 Whipple procedures. Mortality rate was 2.9%. Comparison of these patients to national standards was made in terms of operative mortality, resectability rate, administration of adjuvant therapy, clinical trial participation and overall survival. The results in these patients were comparable to national standards. Conclusions. With adequate commitment of resources and experienced surgical and oncologic practitioners, community cancer centers can meet national tertiary care standards in terms of pancreatic and periampullary cancer care. PMID- 22312533 TI - Feasibility of endoscopic submucosal dissection: a new technique for en bloc resection of a large superficial tumor in the colon and rectum. AB - Endoscopic submucosal dissection (ESD) is a promising procedure that enables en bloc resection of large superficial tumors in the upper gastrointestinal tract. On the other hand, ESD in the colon and rectum is technically difficult to perform because of its anatomical features. At our institution, 137 consecutive superficial colorectal tumors larger than 20 mm in diameter in 137 patients were treated by ESD between April 2007 and October 2010, and 132 lesions were successfully resected. The average procedure time was 79.2 minutes, and the rate of en bloc resection was 89.1% (122/137). The rate of complete resection, defined as en bloc resection with tumor-free lateral and vertical margins, was 85.4% (117/137). The rate of perforation was 3.6% (5/137). Colorectal ESD achieved a high rate of en bloc resection and complete resection and is applicable in the colorectum. PMID- 22312534 TI - Joint symptoms, aromatase inhibitor-related adverse reactions, are indirectly associated with decreased serum estradiol. AB - Background. Joint symptoms (JSs) are problematic adverse drug reactions (ADRs) of aromatase inhibitors (AIs). Involvement of decreased serum estradiol (SE) has been suggested. Patients and Methods. 104 postmenopausal breast cancer patients administered an AI were prospectively investigated regarding various clinical parameters, JS and hot flashes as ADRs, and the SE level. Results. JS manifested in 31.7% of patients and hot flashes in 18.3%. Chi-square testing showed a significantly higher incidence of JS in several patient strata: <55 years old, decreased SE, and elevated total cholesterol (TC). In univariate analysis, JS correlated significantly with a pre-AI % YAM of >=80%, decreased SE, and elevated TC. Eight (7.7%) patients maintained SE at >=5 pg/mL for >6 consecutive months, with no JS. In chi-square testing, hot flashes showed a significantly higher incidence in patients <55 years old. Conclusion. AI-ADRs occurred more readily in younger patients. Decreased SE may be indirectly involved in JS. PMID- 22312535 TI - Can breast self-examination continue to be touted justifiably as an optional practice? AB - In 2003, the revised American Cancer Society guidelines recommended that breast self-examination (BSE) be optional. Of 822 women diagnosed with breast cancer in our hospital from 1994 to 2004, sixty four (7.7%) were 40 years of age or younger. Forty four (68.7%) of these young women discovered their breast cancers on BSE, 17 (18%) by mammography, and 3 (4.7%) by clinical breast examination by medical professionals. Of 758 women over 40 years of age diagnosed with breast cancer, 382 (49%) discovered their cancer by mammography, 278 (39%) by BSE, and 98 (14%) by a clinical breast examination. Lymph node metastases in the older women was one-half that in the younger women (21% versus 42%), and a higher percentage of younger women presented with more advanced disease. In response to increasing breast cancer in young women under 41 years of age, encouragement of proper breast self-examination is warranted and should be advocated. PMID- 22312536 TI - Stereotactic body radiosurgery for spinal metastatic disease: an evidence-based review. AB - Spinal metastasis is a problem that afflicts many cancer patients. Traditionally, conventional fractionated radiation therapy and/or surgery have been the most common approaches for managing such patients. Through technical advances in radiotherapy, high dose radiation with extremely steep drop off can now be delivered to a limited target volume along the spine under image-guidance with very high precision. This procedure, known as stereotactic body radiosurgery, provides a technique to rapidly treat selected spinal metastasis patients with single- or limited-fraction treatments that have similar to superior efficacies compared with more established approaches. This review describes current treatment systems in use to deliver stereotactic body radiosurgery as well as results of some of the larger case series from a number of institutions that report outcomes of patients treated for spinal metastatic disease. These series include nearly 1400 patients and report a cumulative local control rate of 90% with myelopathy risk that is significantly less than 1%. Based on this comprehensive review of the literature, we believe that stereotactic body radiosurgery is an established treatment modality for patients with spinal metastatic disease that is both safe and highly effective. PMID- 22312537 TI - The Changing Face of Mastectomy (from Mutilation to Aid to Breast Reconstruction). AB - Breast cancer is the most common cancer in women. Primary treatment is surgery, with mastectomy as the main treatment for most of the twentieth century. However, over that time, the extent of the procedure varied, and less extensive mastectomies are employed today compared to those used in the past, as excessively mutilating procedures did not improve survival. Today, many women receive breast-conserving surgery, usually with radiotherapy to the residual breast, instead of mastectomy, as it has been shown to be as effective as mastectomy in early disease. The relatively new skin-sparing mastectomy, often with immediate breast reconstruction, improves aesthetic outcomes and is oncologically safe. Nipple-sparing mastectomy is newer and used increasingly, with better acceptance by patients, and again appears to be oncologically safe. Breast reconstruction is an important adjunct to mastectomy, as it has a positive psychological impact on the patient, contributing to improved quality of life. PMID- 22312538 TI - Current insights into surgery for intramedullary spinal cord metastases: a literature review. AB - Intramedullary spinal cord metastasis (ISCM) is the rarest type of CNS involvement by systemic malignant tumours. Optimal management of patients with ISCMs remains ambiguous. Based on two cases reported from our department, we focused on the strategy for intramedullary spinal cord metastases surgery. PMID- 22312539 TI - Metastatic Medulloblastoma in Childhood: Chang's Classification Revisited. AB - Purpose. To correlate the radiological aspects of metastases, the response to chemotherapy, and patient outcome in disseminated childhood medulloblastoma. Patients and Methods. This population-based study concerned 117 newly diagnosed children with disseminated medulloblastoma treated at the Institute Gustave Roussy between 1988 and 2008. Metastatic disease was assessed using the Chang staging system, their form (positive cerebrospinal fluid (CSF), nodular or laminar), and their extension (positive cerebrospinal fluid, local, extensive). All patients received preirradiation chemotherapy. Results. The overall survival did not differ according to Chang M-stage. The 5-year overall survival was 59% in patients with nodular metastases compared to 35% in those with laminar metastases. The 5-year overall survival was 76% in patients without disease at the end of pre-irradiation chemotherapy compared to 34% in those without a complete response (P = 0.0008). Conclusions. Radiological characteristics of metastases correlated with survival in patients with medulloblastoma. Complete response to sandwich chemotherapy was a strong predictor of survival. PMID- 22312540 TI - Current standards in the management of cerebral metastases. AB - The last 30 years have seen major changes in attitude toward patients with cerebral metastases. This paper aims to outline the major landmarks in this transition and the therapeutic strategies currently used. The controversies surrounding control of brain disease are discussed, and two emerging management trends are reviewed: tumor bed radiosurgery and salvage radiation. PMID- 22312541 TI - Sellar and parasellar metastatic tumors. AB - The sellar and parasellar (SPS) region is a complex area rich in vital neurovascular structures and as such may be the location of first manifestation of a systemic malignancy. Metastases to this region are rare; breast cancer is the most common source among those that metastasize to the SPS region. Ophthalmoplegia, headache, retroorbital or facial pain, diabetes insipidus, and visual field defects are the most commonly reported symptoms. Lack of specific clinical and radiological features renders SPS metastases difficult to differentiate from the other frequently encountered lesions in this area, especially when there is no known history of a primary disease. Currently accepted management is multimodality therapy that includes biopsy and/or palliative surgical resection, radiation, and chemotherapy. Although no significant survival benefits have been shown by the surgical series, surgical resection may improve quality of life. Here we review the relevant literature and present six illustrative cases from our own institution. PMID- 22312542 TI - Influence of surgical technique on mastectomy and reexcision rates in breast conserving therapy for cancer. AB - Introduction. Breast conserving surgery (BCS) requires tumor excision with negative margins. Reexcision rates of 30-50% are reported. Ultrasound localization, intraoperative margin pathology, and specimen mammography have reduced reexcisions, but require new equipment. Cavity shave margin (CSM) is a technique, utilizing existing equipment, that potentially reduces reexcision. This study evaluates CSM reexcision impact. Methods. 522 cancers treated with BCS were reviewed. Patients underwent standard partial mastectomy (SPM) or CSM. Data collected included demographics, pathology, and treatments. Results. 455 SPMs were compared to 67 CSMs. Analysis revealed no differences in pathology, intraductal component, or neoadjuvant chemotherapy. Overall reexcision rate = 43%. Most reexcisions were performed for DCIS at margin. SPMs underwent 213 reexcisions (46.8%), versus 16/67 (23.9%) CSMs (P = 0.0003). Total mastectomy as definitive procedure was performed after more SPMs (P = 0.009). Multivariate analysis revealed CSM, % DCIS, tumor size, and race to influence reexcisions. Conclusions. CSM is a technique that reduces reexcisions and mastectomy rates. PMID- 22312543 TI - Implications of Identifying Additional Cerebral Metastases during Gamma Knife Radiosurgery. AB - Introduction. Gamma Knife radiosurgery (GK-SRS) is commonly used to treat cerebral metastases. Although additional intracranial metastases are often found on the day of GK-SRS, the significance of finding them is unknown. Methods. A retrospective review of 133 patients undergoing GK-SRS for cerebral metastases was performed. The change in number of metastases detected between initial referral magnetic resonance imaging (MRI) and subsequent treatment MRI was quantified. Multivariate and Kaplan-Meier analyses were employed to examine the significance of identifying additional lesions. Results. Additional lesions were identified in 41% of patients. An increasing number of metastases on referral MRI (P = 0.001) and the presence of progressive systemic disease (P = 0.003) were predictive of identifying additional metastases. Median survival was 6.9 months for patients with additional metastases, compared to 12.1 months for patients without additional metastases (hazard ratio 1.56, P = 0.021). Conclusions. Identifying additional metastases on the day of GK-SRS may add important prognostic information. PMID- 22312544 TI - Clinical Behavior in Metastatic Brain Disease Is Not Influenced by the Immunological Defense Mediated by CD57 NK-Cells. AB - Objectives. The purpose of the present study is to verify if the degree of immunological response against metastatic tumors, measured by the number of CD57(+) NK-cells in the tissue of a brain metastasis, influences the later development of new brain metastases or tumor recurrence. Patients and Methods. CD57(+) NK-cells were immunohistochemically identified in the resected tumor, in a series of twenty patients operated on by a single brain metastasis secondary to lung adenocarcinoma. In each case, the degree of CD57(+) NK-cells infiltration within the tumor tissue and the period free of new intracranial disease after brain surgery were recorded. Results. All the studied tumors showed variable number of CD57(+) NK-cells (mean +/- standard deviation: 8.4 +/- 4.8 per microscopical field, at 200x). The period free of intracranial disease ranged between 10 and 52 weeks (mean +/- standard deviation: 22.7 +/- 11.9). Statistical analysis showed that there was no correlation between the degree of NK-cells infiltration within the resected tumor and the period free of intracranial disease after surgery (P > 0.05). Conclusion. This finding supports that clinical behavior in metastatic brain disease is not influenced by the immunological response mediated by CD57(+) NK-cells. PMID- 22312545 TI - The role of surgery, radiosurgery and whole brain radiation therapy in the management of patients with metastatic brain tumors. AB - Brain tumors constitute the most common intracranial tumor. Management of brain metastases has become increasingly complex as patients with brain metastases are living longer and more treatment options develop. The goal of this paper is to review the role of stereotactic radiosurgery (SRS), whole brain radiation therapy (WBRT), and surgery, in isolation and in combination, in the contemporary treatment of brain metastases. Surgery and SRS both offer management options that may help to optimize therapy in selected patients. WBRT is another option but can lead to late toxicity and suboptimal local control in longer term survivors. Improved prognostic indices will be critical for selecting the best therapies. Further prospective trials are necessary to continue to elucidate factors that will help triage patients to the proper brain-directed therapy for their cancer. PMID- 22312546 TI - Help Seeking and Access to Primary Care for People from "Hard-to-Reach" Groups with Common Mental Health Problems. AB - Background. In the UK, most people with mental health problems are managed in primary care. However, many individuals in need of help are not able to access care, either because it is not available, or because the individual's interaction with care-givers deters or diverts help-seeking. Aims. To understand the experience of seeking care for distress from the perspective of potential patients from "hard-to-reach" groups. Methods. A qualitative study using semi structured interviews, analysed using a thematic framework. Results. Access to primary care is problematic in four main areas: how distress is conceptualised by individuals, the decision to seek help, barriers to help-seeking, and navigating and negotiating services. Conclusion. There are complex reasons why people from "hard-to-reach" groups may not conceptualise their distress as a biomedical problem. In addition, there are particular barriers to accessing primary care when distress is recognised by the person and help-seeking is attempted. We suggest how primary care could be more accessible to people from "hard-to-reach" groups including the need to offer a flexible, non-biomedical response to distress. PMID- 22312547 TI - Development of a tool to identify poverty in a family practice setting: a pilot study. AB - Objective. The goal of this pilot study was to develop and field-test questions for use as a poverty case-finding tool to assist primary care providers in identifying poverty in clinical practice. Methods. 156 questionnaires were completed by a convenience sample of urban and rural primary care patients presenting to four family practices in British Columbia, Canada. Univariate and multivariate logistic regression analyses compared questionnaire responses with low-income cut-off (LICO) levels calculated for each respondent. Results. 35% of respondents were below the "poverty line" (LICO). The question "Do you (ever) have difficulty making ends meet at the end of the month?" was identified as a good predictor of poverty (sensitivity 98%; specificity 60%; OR 32.3, 95% CI 5.4 191.5). Multivariate analysis identified a 3-item case-finding tool including 2 additional questions about food and housing security (sensitivity 64.3%; specificity 94.4%; OR 30.2, 95% CI 10.3-88.1). 85% of below-LICO respondents felt that poverty screening was important and 67% felt comfortable speaking to their family physician about poverty. Conclusions. Asking patients directly about poverty may help identify patients with increased needs in primary care. PMID- 22312548 TI - Optimizing Liposomal Cisplatin Efficacy through Membrane Composition Manipulations. AB - The first liposomal formulation of cisplatin to be evaluated clinically was SPI 077. Although the formulation demonstrated enhanced cisplatin tumor accumulation in preclinical models it did not enhance clinical efficacy, possibly due to limited cisplatin release from the formulation localized within the tumor. We have examined a series of liposomal formulations to address the in vivo relationship between cisplatin release rate and formulation efficacy in the P388 murine leukemia model. The base formulation of phosphatidylcholine: phosphatidylglycerol: cholesterol was altered in the C18 and C16 phospholipid content to influence membrane fluidity and thereby impacting drug circulation lifetime and drug retention. Phase transition temperatures (T(m)) ranged from 42 55 degrees C. The high T(m) formulations demonstrated enhanced drug retention properties accompanied by low antitumor activity while the lowest T(m) formulations released the drug too rapidly in the plasma, limiting drug delivery to the tumor which also resulted in low antitumor activity. A formulation composed of DSPC : DPPC : DSPG : Chol; (35 : 35 : 20 : 10) with an intermediate drug release rate and a cisplatin plasma half-life of 8.3 hours showed the greatest antitumor activity. This manuscript highlights the critical role that drug release rates play in the design of an optimized drug delivery vehicle. PMID- 22312549 TI - Antibacterial and Antioxidant Properties of the Methanolic Extract of the Stem Bark of Pteleopsis hylodendron (Combretaceae). AB - Pteleopsis hylodendron (Combretaceae) is used in Cameroon and West Africa folk medicine for the treatment of various microbial infections (measles, chickenpox, and sexually transmitted diseases). The antibacterial properties of the methanolic extract and fractions from stem bark of Pteleopsis hylodendron were tested against three Gram-positive bacteria and eight Gram-negative bacteria using Agar-well diffusion and Broth microdilution methods. Antioxidant activities of the crude extract and fractions were investigated by DPPH radical scavenging activity and beta-carotene-linoleic acid assays. The methanolic extract and some fractions exhibited antibacterial activities that varied between the bacterial species (ID = 0.00-25.00 mm; MIC = 781-12500 MUg/mL and 0.24-1000 MUg/mL). The activity of the crude extract is, however, very weak compared to the reference antibiotics (MIC = 0.125-128 MUg/mL). Two fractions (F(E) and F(F)) showed significant activity (MIC = 0.97 MUg/mL) while S. aureus ATCC 25922 was almost resistant to all the tested fractions. In addition, the crude extract and some fractions showed good antioxidant potential with inhibition values ranging from 17.53 to 98.79%. These results provide promising baseline information for the potential use of this plant as well as some of the fractions in the treatment of infectious diseases and oxidative stress. PMID- 22312550 TI - Factors affecting the cost effectiveness of antibiotics. AB - In an era of spiraling health care costs and limited resources, policy makers and health care payers are concerned about the cost effectiveness of antibiotics. The aim of this study is to draw on published economic evaluations with a view to identify and illustrate the factors affecting the cost effectiveness of antibiotic treatment of bacterial infections. The findings indicate that the cost effectiveness of antibiotics is influenced by factors relating to the characteristics and the use of antibiotics (i.e., diagnosis, comparative costs and comparative effectiveness, resistance, patient compliance with treatment, and treatment failure) and by external factors (i.e., funding source, clinical pharmacy interventions, and guideline implementation interventions). Physicians need to take into account these factors when prescribing an antibiotic and assess whether a specific antibiotic treatment adds sufficient value to justify its costs. PMID- 22312551 TI - Activity of Antimicrobial Peptides and Conventional Antibiotics against Superantigen Positive Staphylococcus aureus Isolated from the Patients with Neoplastic and Inflammatory Erythrodermia. AB - Superantigens are proteins comprising a group of molecules produced by various microorganisms. They are involved in pathogenesis of several human diseases. The aim of the study was the comparison of susceptibility to antibiotics and antimicrobial peptides (AMPs) of Staphylococcus aureus (SA) strains producing staphylococcal enterotoxins SEA, SEB, SEC, SED, and TSST-1 and nonproducing ones. In the group of the total 28 of the patients with erythrodermia the presence of SA was confirmed in 24 cases. The total of 14 strains of SA excreted enterotoxins SEA, SEC, SED, and TSST-1. We did not observe that strains producing mentioned superantigens were less susceptible to AMPs (aurein 1.2, citropin 1.1, lipopeptide, protegrin 1, tachyplesin 3, temporin A, and uperin 3.6). The opposite situation was observed in conventional antibiotics. SA strains excreting tested superantigens had higher MICs and MBCs than nonproducing ones. The interesting finding considering the high efficacy of AMPs, against all examined strains of SA, makes them attractive candidates for therapeutic implication. PMID- 22312552 TI - Developing central nervous system and vulnerability to platinum compounds. AB - Comparative studies on the effects of the platinum complexes in use or in clinical trials are carried out in order to discover differences in the neurotoxic potential and the reversibility of neurotoxicity. In this paper, we summarized the current literature on neurotoxicity and chemoresistance of cisplatin (cisPt) and discussed our recent efforts on the interference of cisPt and a new platinum compound [Pt(O,O'-acac)(gamma-acac)(DMS)] (PtAcacDMS), with high specific reactivity with sulphur ligands instead of nucleobases as cisPt, on some crucial events of rat postnatal cerebellum development. The acute effects of drug treatments on cell proliferation and death in the external granular layer and granule cell migration and the late effects on the dendrite growth of Purkinje cells were evaluated. Together with the demonstrated antineoplastic effectiveness in vitro, compared with cisPt, data suggest a lower neurotoxicity of PtAcacDMS, in spite of its presence in the brain that involves considerations on the blood brain barrier permeability. PMID- 22312553 TI - Cardiac Conduction Safety during Coadministration of Artemether-Lumefantrine and Lopinavir/Ritonavir in HIV-Infected Ugandan Adults. AB - Background. We aimed to assess cardiac conduction safety of coadministration of the CYP3A4 inhibitor lopinavir/ritonavir (LPV/r) and the CYP3A4 substrate artemether-lumefantrine (AL) in HIV-positive Ugandans. Methods. Open-label safety study of HIV-positive adults administered single-dose AL (80/400 mg) alone or with LPV/r (400/100 mg). Cardiac function was monitored using continuous electrocardiograph (ECG). Results. Thirty-two patients were enrolled; 16 taking LPV/r -based ART and 16 ART naive. All took single dose AL. No serious adverse events were observed. ECG parameters in milliseconds remained within normal limits. QTc measurements did not change significantly over 72 hours although were higher in LPV/r arm at 24 (424 versus 406; P = .02) and 72 hours (424 versus 408; P = .004) after AL intake. Conclusion. Coadministration of single dose of AL with LPV/r was safe; however, safety of six-dose AL regimen with LPV/r should be investigated. PMID- 22312554 TI - Bevacizumab improves quality of life in patients with recurrent glioblastoma. AB - Objective. To quantify the benefits in survival and quality of life in patients receiving bevacizumab (BEV) for recurrent glioblastoma (GBM). Methods. This is a retrospective study of 40 adult patients with recurrent GBM treated between 2005 and 2009 at a single institution. All patients had initial treatment with surgery, radiation, and concurrent temozolomide, then monthly temozolomide. Over 250 charts were screened. Sufficient data was available for 20 patients treated with BEV and 20 patients who did not receive BEV at the time of recurrence. The independent living score (ILS), designed to reward long-term independent survival, was calculated for each patient. Results. The mean ILS was nearly double in the BEV group compared to the No-BEV group (15.0 versus 8.2, P = 0.002, t-test). Two months after initiation of therapy, the median steroid dose dropped by over 90% in patients treated with BEV, but doubled in the NoBEV group. Median survival from the time of recurrence was significantly affected: 10.6 months in the BEV group versus 4.2 months (P < 0.001, log rank survival) in the NoBEV group. Conclusions. BEV increases independent living and lengthens overall survival after GBM recurrence. Reduction in steroid dose may contribute to prolonged independence. PMID- 22312555 TI - Antibiotic Combinations with Daptomycin for Treatment of Staphylococcus aureus Infections. AB - Daptomycin is a lipopeptide antibiotic with a unique mechanism of action on Gram positive bacteria. It is approved for treatment of skin and soft-tissue infections with Gram-positive bacteria, bacteraemia and right-sided infective endocarditis caused by Staphylococcus aureus. Diminishing susceptibility of S. aureus to daptomycin during treatment of complicated infections and clinical failure have been described. Combinations of daptomycin with other antibiotics including gentamicin, rifampin, beta-lactams, trimethoprim/sulfamethoxazole (TMP SMX), or clarithromycin present a new approach for therapy. In vitro and animal studies have shown that such combinations may, in some cases, be superior to daptomycin monotherapy. In this paper we focus on the antibiotic combinations for complicated S. aureus infections. PMID- 22312556 TI - Triple-negative breast cancer: adjuvant therapeutic options. AB - Triple-negative breast cancer (TNBC), a subtype distinguished by negative immunohistochemical assays for expression of the estrogen and progesterone receptors (ER/PR) and human epidermal growth factor receptor-2(HER2) represents 15% of all breast cancers. Patients with TNBC generally experience a more aggressive clinical course with increased risk of disease progression and poorer overall survival. Furthermore, this subtype accounts for a disproportionate number of disease-related mortality in part due to its aggressive natural history and our lack of effective targeted agents beyond conventional cytotoxic chemotherapy. In this paper, we will review the epidemiology, risk factors, prognosis, and the molecular and clinicopathologic features that distinguish TNBC from other subtypes of breast cancer. In addition, we will examine the available data for the use of cytotoxic chemotherapy in the treatment of TNBC in both the neoadjuvant and adjuvant setting and explore the ongoing development of newer targeted agents. PMID- 22312557 TI - The Role of Wild-Type p53 in Cisplatin-Induced Chk2 Phosphorylation and the Inhibition of Platinum Resistance with a Chk2 Inhibitor. AB - The major obstacle in platinum chemotherapy is the repair of platinum-damaged DNA that results in increased resistance, reduced apoptosis, and finally treatment failure. Our research goal is to determine and block the mechanisms of platinum resistance. Our recent studies demonstrate that several kinases in the DNA-repair pathway are activated after cells are exposed to cisplatin. These include ATM, p53, and Chk2. The increased Chk2 phosphorylation is modulated by p53 in a wild type p53 model. Overexpression of p53 by cDNA transfection in wt-p53 (but not p53 deficient) cells doubled the amount of Chk2 phosphorylation 48 hours after cisplatin treatment. p53 knockdown by specific siRNA greatly reduced Chk2 phosphorylation. We conclude that wild-type p53, in response to cisplatin stimulation, plays a role in the upstream regulation of Chk2 phosphorylation at Thr-68. Cells without normal p53 function survive via an alternative pathway in response to the exogenous influence of cisplatin. We strongly suggest that it is very important to include the p53 mutational status in any p53 involved studies due to the functional differentiation of wt p53 and p53 mutant. Inhibition of Chk2 pathway with a Chk2 inhibitor (C3742) increased cisplatin efficacy, especially those with defective p53. Our findings suggest that inhibition of platinum resistance can be achieved with a small-molecule inhibitor of Chk2, thus improving the therapeutic indices for platinum chemotherapy. PMID- 22312558 TI - Current chemotherapeutic management of patients with gestational trophoblastic neoplasia. AB - Gestational trophoblastic neoplasia (GTN) describes a heterogeneous group of interrelated lesions that arise from abnormal proliferation of placental trophoblasts. GTN lesions are histologically distinct, malignant lesions that include invasive hydatidiform mole, choriocarcinoma, placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT). GTN tumors are generally highly responsive to chemotherapy. Early stage GTN disease is often cured with single-agent chemotherapy. In contrast, advanced stage disease requires multiagent combination chemotherapeutic regimens to achieve a cure. Various adjuvant surgical procedures can be helpful to treat women with GTN. Patients require careful followup after completing treatment and recurrent disease should be aggressively managed. Women with a history of GTN are at increased risk of subsequent GTN, hence future pregnancies require careful monitoring to ensure normal gestational development. This article will review the workup, management and followup of women with all stages of GTN as well as with recurrent disease. PMID- 22312559 TI - Neurotoxicity caused by the treatment with platinum analogues. AB - Platinum agents (cisplatin, carboplatin, and oxaliplatin) are a class of chemotherapy agents that have a broad spectrum of activity against several solid tumors. Toxicity to the peripheral nervous system is the major dose-limiting toxicity of at least some of the platinum drugs of clinical interest. Among the platinum compounds in clinical use, cisplatin is the most neurotoxic, inducing mainly sensory neuropathy of the upper and lower extremities. Carboplatin is generally considered to be less neurotoxic than cisplatin, but it is associated with a higher risk of neurological dysfunction if administered at high dose or in combination with agents considered to be neurotoxic. Oxaliplatin induces two types of peripheral neuropathy, acute and chronic. The incidence of oxaliplatin induced neuropathy is related to various risk factors such as treatment schedule, cumulative dose, and time of infusion. To date, several neuroprotective agents including thiol compounds, vitamin E, various anticonvulsants, calcium-magnesium infusions, and other nonpharmacological strategies have been tested for their ability to prevent platinum-induced neurotoxicity with controversial results. Further studies on the prevention and treatment of neurotoxicity of platinum analogues are warranted. PMID- 22312560 TI - Nedaplatin: a radiosensitizing agent for patients with cervical cancer. AB - Despite the recent advances in the management of cervical cancer using cisplatin based concurrent chemoradiotherapy, substantial treatment failure still occurs, especially in advanced-stage patients and early-stage cervical cancer patients with high-risk prognostic factors. Therefore, efforts to further improve the survival and quality of life of these patients are necessary. Nedaplatin (cis diammine-glycoplatinum), a derivative of cisplatin, was developed with the aim of producing a treatment with a similar effectiveness to cisplatin but decreased renal and gastrointestinal toxicities. Based on the promising results of preclinical studies, the clinical efficacy of nedaplatin as a radiosensitizing agent was evaluated in patients with cervical cancer. Retrospective analysis of nedaplatin-based concurrent chemoradiotherapy (CCRT) against cervical cancer suggested that nedaplatin-based CCRT can be considered as an alternative to cisplatin-based CCRT in both early-stage and advanced-stage cervical cancer patients. However, due to the lack of a randomized controlled study, nedaplatin based CCRT has not been convincingly proven to be clinically effective in patients with cervical cancer. Further investigations in randomized controlled trials are therefore needed. PMID- 22312561 TI - Susceptibility of bifidobacteria of animal origin to selected antimicrobial agents. AB - Strains of the genus Bifidobacterium are frequently used as probiotics, for which the absence of acquired antimicrobial resistance has become an important safety criterion. This clarifies the need for antibiotic susceptibility data for bifidobacteria. Based on a recently published standard for antimicrobial susceptibility testing of bifidobacteria with broth microdilution method, the range of susceptibility to selected antibiotics in 117 animal bifidobacterial strains was examined. Narrow unimodal MIC distributions either situated at the low-end (chloramphenicol, linezolid, and quinupristin/dalfopristin) or high-end (kanamycin, neomycin) concentration range could be detected. In contrast, the MIC distribution of trimethoprim was multimodal. Data derived from this study can be used as a basis for reviewing or verifying present microbiological breakpoints suggested by regulatory agencies to assess the safety of these micro-organisms intended for the use in probiotics. PMID- 22312562 TI - Evaluation of antiproliferative activity of red sorghum bran anthocyanin on a human breast cancer cell line (mcf-7). AB - Breast cancer is a leading cause of death in women worldwide both in the developed and developing countries. Thus effective treatment of breast cancer with potential antitumour drugs is important. In this paper, human breast cancer cell line MCF-7 has been employed to evaluate the antiproliferative activity of red sorghum bran anthocyanin. The present investigation showed that red sorghum bran anthocyanin induced growth inhibition of MCF-7 cells at significant level. The growth inhibition is dose dependent and irreversible in nature. When MCF-7 cells were treated with red sorghum bran anthocyanins due to activity of anthocyanin morphological changes were observed. The morphological changes were identified through the formation of apoptopic bodies. The fragmentation by these anthocyanins on DNA to oligonuleosomal-sized fragments, is a characteristic of apoptosis, and it was observed as concentration-dependent. Thus, this paper clearly demonstrates that human breast cancer cell MCF-7 is highly responsive by red sorghum bran anthocyanins result from the induction of apoptosis in MCF-7 cells. PMID- 22312563 TI - Cervical spondylotic myelopathy: factors in choosing the surgical approach. AB - Cervical spondylotic myelopathy is a progressive disease and a common cause of acquired disability in the elderly. A variety of surgical interventions are available to halt or improve progression of the disease. Surgical options include anterior or posterior approaches with and without fusion. These include anterior cervical discectomy and fusion, anterior cervical corpectomy and fusion, cervical disc replacement, laminoplasty, laminectomy with and without fusion, and combined approaches. Recent investigation into the ideal approach has not found a clearly superior choice, but individual patient characteristics can guide treatment. PMID- 22312564 TI - Oxygen Kinetics and Heart Rate Response during Early Recovery from Exercise in Patients with Heart Failure. AB - Background. The purpose of this study was to assess the post-exercise O(2) uptake and heart rate response in patients with heart failure (HF) in comparison to healthy individuals. Methods and Results. Exercise testing of all subjects was conducted according to the RITE-protocol. The study subjects were classified according to their peak oxygen uptake (peak VO(2)) in four groups: healthy individuals with a peak VO(2) >22 mL/kg/min (group 1, n: 50), and patients with HF and a peak VO(2) of 18-22 mL/kg/min, (group 2, n: 48), 14-18 mL/kg/min (group 3, n: 57), and <14 mL/kg/min (group 4, n: 31). Both peak VO(2) and HR declined more slowly in the patients with HF than in the normal subjects. Recovery of VO(2) and HR followed monoexponential kinetics in the early post-recovery phase. This enabled the determination of a time constant for both HR and VO(2) (TC VO(2) and TC HR). From group 1 to 4 there was a prolongation of the time constant for VO(2) and HR: TC VO(2) (group 1: 110 +/- 34, group 2: 197 +/- 43, group 3: 238 +/ 80, and group 4: 278 +/- 50 sec), and TC HR (group 1: 148 +/- 82, group 2: 290 +/- 65, group 3: 320 +/- 58, and group 4: 376 +/- 55 sec). Conclusion. The rate of decline of VO(2) and HR in the early post-exercise phase is inversely related to the peak VO(2). The time constant for oxygen uptake (TC VO(2)) and heart rate (TC HR) might prove a useful parameter for more precise monitoring and grading of HF. PMID- 22312565 TI - Knowledge and Misconceptions about Malaria among Pregnant Women in a Post Conflict Internally Displaced Persons' Camps in Gulu District, Northern Uganda. AB - Background. In Uganda Malaria continues to be a major public health problem accounting for about 30-50% of all outpatient consultations and 35% of hospital admissions and a leading cause of mortality and morbidity. Pregnant women and their unborn children are vulnerable to malaria. Methods. A cross-sectional survey was conducted in 20 postconflict IDP camps of Gulu district selected randomly as clusters. 769 pregnant women were interviewed. Results. The majority of the respondents 85% have ever heard about malaria. Most (80%) 571 respondent attributed malaria to be transmitted by mosquito bites, 15 said cold weather, 53 said dirt, and 35 said not sleeping under net. Most (91%) 683 respondents mentioned that malaria was caused by mosquito, 28 mentioned cold food, 3 mentioned playing in the rain, 19 mentioned cold weather, and 6 mentioned eating mangos. Conclusion. Most pregnant women in the post conflict IDP camps have relatively high knowledge about malaria transmission, signs, symptoms, and consequences during pregnancy. However, majority of respondents had misconception about the cause of malaria while a few had misconception about the mode of malaria transmission. PMID- 22312566 TI - Mapping malaria transmission risk in northern morocco using entomological and environmental data. AB - Malaria resurgence risk in Morocco depends, among other factors, on environmental changes as well as the introduction of parasite carriers. The aim of this paper is to analyze the receptivity of the Loukkos area, large wetlands in Northern Morocco, to quantify and to map malaria transmission risk in this region using biological and environmental data. This risk was assessed on entomological risk basis and was mapped using environmental markers derived from satellite imagery. Maps showing spatial and temporal variations of entomological risk for Plasmodium vivax and P. falciparum were produced. Results showed this risk to be highly seasonal and much higher in rice fields than in swamps. This risk is lower for Afrotropical P. falciparum strains because of the low infectivity of Anopheles labranchiae, principal malaria vector in Morocco. However, it is very high for P. vivax mainly during summer corresponding to the rice cultivation period. Although the entomological risk is high in Loukkos region, malaria resurgence risk remains very low, because of the low vulnerability of the area. PMID- 22312567 TI - Pattern of the Antimalarials Prescription during Pregnancy in Bangui, Central African Republic. AB - Introduction. The aim of this study was to identify the antimalarials prescribed during the pregnancy and to document their timing. Method. From June to September 2009, a survey was conducted on 565 women who gave birth in the Castors maternity in Bangui. The antenatal clinics cards were checked in order to record the types of antimalarials prescribed during pregnancy according to gestational age. Results. A proportion of 28.8% ANC cards contained at least one antimalarial prescription. The commonest categories of antimalarials prescribed were: quinine (56.7%), artemisinin-based combinations (26.8%) and artemisinin monotherapy (14.4%). Among the prescriptions that occurred in the first trimester of pregnancy, artemisinin-based combinations and artemisinin monotherapies represented the proportions of (10.9%) and (13.3%). respectively. Conclusion. This study showed a relatively high rate (>80%) of the recommended antimalarials prescription regarding categories of indicated antimalarials from national guidelines. But, there is a concern about the prescription of the artemisinin derivatives in the first trimester of pregnancy, and the prescription of artemisinin monotherapy. Thus, the reinforcement of awareness activities of health care providers on the national malaria treatment during pregnancy is suggested. PMID- 22312569 TI - In vitro antiplasmodial activity and cytotoxicity of extracts of selected medicinal plants used by traditional healers of Western cameroon. AB - Medicinal plants play a key role in malaria control in Africa, especially in remote areas where health facilities are limited. In order to assess their acclaimed potentials, eleven extracts were prepared from seven selected plants commonly used in Western Cameroon, and tested both for their antiplasmodial activity and cytotoxicity. The antiplasmodial activity was assessed using Lactate Dehydrogenase Assay (pLDH) and the cytotoxicity estimated on LLC-MK2 monkey kidney epithelial cells. Seven extracts from five different plants were significantly active, with very weak or no cytotoxicity. The Dacryodes edulis leaves showed the highest activity (IC(50) of 6.45 MUg/mL on 3D7 and 8.2 MUg/mL on DD2) followed by the leaves of Vernonia amygdalina (IC(50) of 8.72 and 11.27 MUg/mL on 3D7 and DD2 resp.) and roots of V. amygdalina (IC(50) of 8.72 MUg/mL on 3D7), Coula edulis leaves (IC(50) of 13.80 MUg/mL and 5.79 MUg/mL on 3D7 and DD2 resp.), Eucalyptus globulus leaves (IC(50) of 16.80 MUg/mL and 26.45 MUg/mL on 3D7 and DD2) and Cuviera longiflora stem bark (IC(50) of 20.24 MUg/mL and 13.91 MUg/mL on 3D7 and DD2). These findings justify the use of five of the seven plants in malaria treatment by traditional healers of Western Cameroon. PMID- 22312570 TI - Characterization of the Duffy-Binding-Like Domain of Plasmodium falciparum Blood Stage Antigen 332. AB - Studies on Pf332, a major Plasmodium falciparum blood-stage antigen, have largely been hampered by the cross-reactive nature of antibodies generated against the molecule due to its high content of repeats, which are present in other malaria antigens. We previously reported the identification of a conserved domain in Pf332 with a high degree of similarity to the Duffy-binding-like (DBL) domains of the erythrocyte-binding-like (EBL) family. We here describe that antibodies towards Pf332-DBL are induced after repeated exposure to P. falciparum and that they are acquired early in life in areas of intense malaria transmission. Furthermore, a homology model of Pf332-DBL was found to be similar to the structure of the EBL-DBLs. Despite their similarities, antibodies towards Pf332 DBL did not display any cross-reactivity with EBL-proteins as demonstrated by immunofluorescence microscopy, Western blotting, and peptide microarray. Thus the DBL domain is an attractive region to use in further studies on the giant Pf332 molecule. PMID- 22312571 TI - Malaria treatment policy change and implementation: the case of Uganda. AB - Malaria due to P. falciparum is the number one cause of morbidity and mortality in Uganda where it is highly endemic in 95% of the country. The use of efficacious and effective antimalarial medicines is one of the key strategies for malaria control. Until 2000, Chloroquine (CQ) was the first-line drug for treatment of uncomplicated malaria in Uganda. Due to progressive resistance to CQ and to a combination of CQ with Sulfadoxine-Pyrimethamine, Uganda in 2004 adopted the use of ACTs as first-line drug for treating uncomplicated malaria. A review of the drug policy change process and postimplementation reports highlight the importance of managing the policy change process, generating evidence for policy decisions and availability of adequate and predictable funding for effective policy roll-out. These and other lessons learnt can be used to guide countries that are considering anti-malarial drug change in future. PMID- 22312572 TI - Factors Associated with Use of Guideline in Home Management of Malaria among Children in Rural South West Nigeria. AB - The dosage regimen for artemether-lumefantrine which is the standard of care for malaria in most of Sub-Saharan countries requires use of treatment guidelines and instructions to enhance caregivers' performance in the treatment of malaria. As part of a larger study evaluating its effectiveness in a rural local government area in southwestern Nigeria, 552 caregivers whose children had fever two weeks preceeding the survey were recruited. Information was collected with interviewer administered questionnaire. A multilevel logistic regression model was fitted using the gllamm approach in Stata to determine the factors associated with use of guideline. Age and educational background of caregiver were significantly associated with guideline use. Caregivers aged 26-30 years were 4 times more likely to use guideline than those aged >40 years. Caregivers with primary education were 4 times more likely to use guideline compared with caregivers with no formal education. Between-village variance was 0.00092 +/- 0.3084. Guideline use reduced with increasing age and lower education. PMID- 22312573 TI - Artemether-Lumefantrine Combination Therapy for Treatment of Uncomplicated Malaria: The Potential for Complex Interactions with Antiretroviral Drugs in HIV Infected Individuals. AB - Treatment of malaria in HIV-infected individuals receiving antiretroviral therapy (ART) poses significant challenges. Artemether-lumefantrine (AL) is one of the artemisisnin-based combination therapies recommended for treatment of malaria. The drug combination is highly efficacious against sensitive and multidrug resistant falciparum malaria. Both artemether and lumefantrine are metabolized by hepatic cytochrome P450 (CYP450) enzymes which metabolize the protease inhibitors (PIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) used for HIV treatment. Coadministration of NNRTIs and PIs with AL could potentially cause complex pharmacokinetic drug interactions. NNRTI by inducing CYP450 3A4 enzyme and PIs by inhibiting CYP450 3A4 enzymes could influence both artemether and lumefantrine concentrations and their active metabolites dihydroartemisinin and desbutyl-lumefantrine, predisposing patients to poor treatment response, toxicity, and risk for development of resistance. There are scanty data on these interactions and their consequences. Pharmacokinetic studies to evaluate these interactions in the target populations are urgently needed. PMID- 22312574 TI - Plasmodium falciparum: Assessment of Selectivity of Action of Chloroquine, Alchornea cordifolia, Ficus polita, and Other Drugs by a Tetrazolium-Based Colorimetric Assay. AB - A tetrazolium-based colorimetric selective assay (MTT-based CSA) was developed to assess the selectivity of antimalarial drugs. This in vitro assay, unlike all others, measures the ability of drugs to indirectly protect red blood cells (RBCs) from Plasmodium-falciparum-induced destruction. Optimum incubation time and number of cells needed were 5 days and 23 * 10(6) RBCs per well, respectively. A parasitemia range of 0.375% to 3% was found to be suitable for this assay. The MTT-based CSA determined anti-P. falciparum strain DD2 activity of chloroquine at a higher 50% effective concentration (EC(50)) value (21.0 MUg/mL) than the isotopic microtest (10.0 MUg/mL). Artesunate and oxytetracycline achieved 90% effect against DD2 with minimal or no toxicity to RBCs. Against chloroquine sensitive strain 3D7, chloroquine and Alchornea cordifolia had EC(50) values of 0.025 MUg/mL and 4.9 MUg/mL respectively, and selective index (SI) values of >2,000 and >69.4 MUg/mL, respectively. PMID- 22312575 TI - Parasitologic Assessment of Two-Dose and Monthly Intermittent Preventive Treatment of Malaria during Pregnancy with Sulphadoxine-Pyrimethamine (IPTP-SP) in Lagos, Nigeria. AB - Intermittent preventive treatment of malaria with sulphadoxine-pyrimethamine (IPTP-SP) is a key strategy in the control of malaria in pregnancy. However, reports of increasing level of resistance to SP using nonpregnant populations have made it imperative for the continuous monitoring of the efficacy of SP in pregnant women. This study assessed using microscopy, monthly dosing and the standard two-dose regimen among 259 pregnant women attending antenatal clinics in Lagos, Nigeria that consented 122 in the two-dose arm (Arm A) and 137 in the monthly dose arm (Arm B). Baseline parasitaemia in the two groups was 5 (4.1%) and 3 (2.2%) in Arms A and B, respectively. Few of the women developed parasitaemia after the initial SP dose in Arms A 4 (3.3%) and B 2 (1.5%). However, none of the women had malaria infection after the second dose in both Arms. Although IPTP-SP is suggestive of protecting the women from malaria infection, there was no significant difference observed between the two dosing schemes. PMID- 22312576 TI - The efficacy of image correlation spectroscopy for characterization of the extracellular matrix. AB - Image correlation spectroscopy (ICS) is known to be a useful tool for the evaluation of fiber width in the extracellular matrix. Here we evaluate a more general from of ICS fit parameters for fiber networks and arrive at a means of quantifying the fiber density, pore size and length which facilitates the characterization of the extracellular matrix. A simulation package was made to create images with different structural properties of fiber networks such as fiber orientation, width, fiber density and length. A pore finding algorithm was developed which determines the distribution of circular voids in the image. Collagen I hydrogels were prepared under different polymerization conditions for validation of our pore size algorithm with microscopy data. ICS parameters included amplitude, standard deviation and ellipticity and are shown to predict the structural properties of fiber networks in a quantitative manner. While the fiber width is related to the ICS sigma; the fiber density relates to the pore size distribution which correlates with the ICS amplitude in thresholded images. Fiber length is related to ICS ellipticity if the fibers have a preferred orientation. Findings from ICS and pore distribution algorithms were verified for both simulated and microscopy data. Based on these findings, we conclude that ICS can be used in the assessment of the extracellular matrix and the prediction of fiber orientation, width, density, length and matrix pore size. PMID- 22312577 TI - Adaptive optics with pupil tracking for high resolution retinal imaging. AB - Adaptive optics, when integrated into retinal imaging systems, compensates for rapidly changing ocular aberrations in real time and results in improved high resolution images that reveal the photoreceptor mosaic. Imaging the retina at high resolution has numerous potential medical applications, and yet for the development of commercial products that can be used in the clinic, the complexity and high cost of the present research systems have to be addressed. We present a new method to control the deformable mirror in real time based on pupil tracking measurements which uses the default camera for the alignment of the eye in the retinal imaging system and requires no extra cost or hardware. We also present the first experiments done with a compact adaptive optics flood illumination fundus camera where it was possible to compensate for the higher order aberrations of a moving model eye and in vivo in real time based on pupil tracking measurements, without the real time contribution of a wavefront sensor. As an outcome of this research, we showed that pupil tracking can be effectively used as a low cost and practical adaptive optics tool for high resolution retinal imaging because eye movements constitute an important part of the ocular wavefront dynamics. PMID- 22312578 TI - Investigation of the isoplanatic patch and wavefront aberration along the pupillary axis compared to the line of sight in the eye. AB - Conventional optical systems usually provide best image quality on axis, while showing unavoidable gradual decrease in image quality towards the periphery of the field. The optical system of the human eye is not an exception. Within a limiting boundary the image quality can be considered invariant with field angle, and this region is known as the isoplanatic patch. We investigate the isoplanatic patch of eight healthy eyes and measure the wavefront aberration along the pupillary axis compared to the line of sight. The results are used to discuss methods of ocular aberration correction in wide-field retinal imaging with particular application to multi-conjugate adaptive optics systems. PMID- 22312579 TI - Noninvasive diffuse optical monitoring of head and neck tumor blood flow and oxygenation during radiation delivery. AB - This study explored using a novel diffuse correlation spectroscopy (DCS) flow oximeter to noninvasively monitor blood flow and oxygenation changes in head and neck tumors during radiation delivery. A fiber-optic probe connected to the DCS flow-oximeter was placed on the surface of the radiologically/clinically involved cervical lymph node. The DCS flow-oximeter in the treatment room was remotely operated by a computer in the control room. From the early measurements, abnormal signals were observed when the optical device was placed in close proximity to the radiation beams. Through phantom tests, the artifacts were shown to be caused by scattered x rays and consequentially avoided by moving the optical device away from the x-ray beams. Eleven patients with head and neck tumors were continually measured once a week over a treatment period of seven weeks, although there were some missing data due to the patient related events. Large inter-patient variations in tumor hemodynamic responses were observed during radiation delivery. A significant increase in tumor blood flow was observed at the first week of treatment, which may be a physiologic response to hypoxia created by radiation oxygen consumption. Only small and insignificant changes were found in tumor blood oxygenation, suggesting that oxygen utilizations in tumors during the short period of fractional radiation deliveries were either minimal or balanced by other effects such as blood flow regulation. Further investigations in a large patient population are needed to correlate the individual hemodynamic responses with the clinical outcomes for determining the prognostic value of optical measurements. PMID- 22312580 TI - Mitochondrial redox studies of oxidative stress in kidneys from diabetic mice. AB - Chronic hyperglycemia during diabetes leads to increased production of reactive oxygen species (ROS) and increased oxidative stress (OS). Here we investigated whether changes in the metabolic state can be used as a marker of OS progression in kidneys. We examined redox states of kidneys from diabetic mice, Akita(/+) and Akita(/+);TSP1(-/-) mice (Akita mice lacking thrombospondin-1, TSP1) with increasing duration of diabetes. OS as measured by mitochondrial redox ratio (NADH/FAD) was detectable shortly after the onset of diabetes and further increased with the duration of diabetes. Thus, cryo fluorescence redox imaging was used as a quantitative marker of OS progression in kidneys from diabetic mice and demonstrated that alterations in the oxidative state of kidneys occur during the early stages of diabetes. PMID- 22312581 TI - Quantitative comparison of contrast and imaging depth of ultrahigh-resolution optical coherence tomography images in 800-1700 nm wavelength region. AB - We investigated the wavelength dependence of imaging depth and clearness of structure in ultrahigh-resolution optical coherence tomography over a wide wavelength range. We quantitatively compared the optical properties of samples using supercontinuum sources at five wavelengths, 800 nm, 1060 nm, 1300 nm, 1550 nm, and 1700 nm, with the same system architecture. For samples of industrially used homogeneous materials with low water absorption, the attenuation coefficients of the samples were fitted using Rayleigh scattering theory. We confirmed that the systems with the longer-wavelength sources had lower scattering coefficients and less dependence on the sample materials. For a biomedical sample, we observed wavelength dependence of the attenuation coefficient, which can be explained by absorption by water and hemoglobin. PMID- 22312582 TI - The integration of a micropipette in a closed microfluidic chip with optical tweezers for investigations of single cells: erratum. AB - In July 2011 a new concept of a closed microfluidic system equipped with a fixed micropipette, optical tweezers and a UV-Vis spectrometer was presented [Biomed. Opt. Express 2, 2299 (2011)]. Figure 1 showed falsely oriented mirrors. To clarify the design of the setup, this erratum presents a correct schematic. PMID- 22312583 TI - Correlating light scattering with internal cellular structures. AB - The origins of side scattering from a fibroblast and cervical cell line were determined by comparing side-scatter images with images stained for lysosomes, nuclei, and mitochondria on a cell by cell basis. Lysosomes or nuclei are the most efficient type of scatterer depending on the cell type and incident light polarization. The relative scattering efficiencies of lysosomes and mitochondria were the same for both cell lines, while the scattering efficiencies of the nuclei differed. The percent of 90 degrees scattering from the nucleus, mitochondria, and lysosomes as well as the group of other internal cellular objects was estimated. The nucleus was the largest contributor to side scatter in the cervical carcinoma cells. The contributions of lysosomes, mitochondria, the nucleus, and particles unstained by either Hoechst, LysoSensor or MitoTracker ranges from ~20% to ~30% in fibroblast cells. The contribution of lysosomes to side scatter was much stronger when the incident light was polarized perpendicular to the scattering plane than when the polarization of the side scatter laser was parallel to the scattering plane. This dependence on side scatter polarization indicates that lysosomes contain scattering structures that are much smaller than the wavelength of light used in the measurements (785 nm). In conclusion, mitochondria were not found to be either the most efficient scatterer or to have the largest contribution to scattering in either cell line, in contrast to previous reports. Rather lysosomes, nuclei and unknown particles all have significant contributions to 90 degrees scattering and the contributions of some of these particles can be modulated by changing the polarization of the incident light. PMID- 22312584 TI - Enhanced robustness digital holographic microscopy for demanding environment of space biology. AB - We describe an optimized digital holographic microscopy system (DHM) suitable for high-resolution visualization of living cells under conditions of altered macroscopic mechanical forces such as those that arise from changes in gravitational force. Experiments were performed on both a ground-based microgravity simulation platform known as the random positioning machine (RPM) as well as during a parabolic flight campaign (PFC). Under these conditions the DHM system proved to be robust and reliable. In addition, the stability of the system during disturbances in gravitational force was further enhanced by implementing post-processing algorithms that best exploit the intrinsic advantages of DHM for hologram autofocusing and subsequent image registration. Preliminary results obtained in the form of series of phase images point towards sensible changes of cytoarchitecture under states of altered gravity. PMID- 22312585 TI - Exploratory Dijkstra forest based automatic vessel segmentation: applications in video indirect ophthalmoscopy (VIO). AB - We present a methodology for extracting the vascular network in the human retina using Dijkstra's shortest-path algorithm. Our method preserves vessel thickness, requires no manual intervention, and follows vessel branching naturally and efficiently. To test our method, we constructed a retinal video indirect ophthalmoscopy (VIO) image database from pediatric patients and compared the segmentations achieved by our method and state-of-the-art approaches to a human drawn gold standard. Our experimental results show that our algorithm outperforms prior state-of-the-art methods, for both single VIO frames and automatically generated, large field-of-view enhanced mosaics. We have made the corresponding dataset and source code freely available online. PMID- 22312586 TI - Detection of single fluorescent proteins inside eukaryotic cells using two-photon fluorescence. AB - Imaging single fluorescent proteins in a live cell is a challenging task because of the strong cellular autofluorescence. Autofluorescence can be minimized by reducing fluorescence excitation volume. Total internal reflection fluorescence (TIRF) microscopy has been routinely used to reduce excitation volume and detect single protein molecules in or close to cell membrane. However, the limited penetration depth of evanescent field excludes imaging of single fluorescent proteins that reside deep inside a eukaryotic cell. Here we report detection of single fluorescent proteins inside eukaryotic cells by two-photon fluorescence (TPF) microscopy. TPF has an excitation volume less than 0.1 femtoliter (fL). Cell autofluorescence under TPF is low and thus enables us to detect single enhanced green fluorescent proteins (EGFP) and single monomeric teal fluorescent proteins (mTFP1.0) that reside several microns deep inside the cell. Discrete stepwise photobleaching of TPF was observed for both proteins inside the cell. Quantitative analysis of single-molecule fluorescence trajectories show that mTFP1.0 is about twofold brighter than EGFP, while its fluorescence on-time before bleaching is about 10 fold shorter. These findings demonstrate the sensitivity of TPF for imaging of eukaryotic cells at single-molecule level and will be useful for measurement of protein stoichiometry inside the cell. PMID- 22312587 TI - Scanning and non-scanning surface plasmon microscopy to observe cell adhesion sites. AB - We observe adhesion sites of a cell on a substrate with high resolution. Since this observation requires interfacial measurements between the cell and the substrate, we employ scanning localized surface plasmon microscopy. We experimentally show that focal adhesion sites of a mouse muscle cell can be observed without fluorescent labeling. We also show that a non-scanning surface plasmon microscope combined with the scanning localized surface plasmon microscope contributes to observing an entire cell adhesion site and identify regions of interest. PMID- 22312588 TI - Label-free imaging of zebrafish larvae in vivo by photoacoustic microscopy. AB - Zebrafish play an important role in biological and biomedical research. Traditional in vivo imaging methods for studying zebrafish larvae primarily require fluorescence labeling. In this work, relying on tissue intrinsic optical absorption contrast, we acquired high resolution label-free 3D images of zebrafish larvae by using photoacoustic microscopy (PAM) in vivo. The spatial resolution reaches several microns, allowing the study of microstructures in various living organs. We demonstrated that our method has the potential to be a powerful non-invasive imaging method for studying various small animal models, including zebrafish larvae, Caenorhabditis elegans, frogs and drosophila larvae. PMID- 22312589 TI - Parametric imaging of the local attenuation coefficient in human axillary lymph nodes assessed using optical coherence tomography. AB - We report the use of optical coherence tomography (OCT) to determine spatially localized optical attenuation coefficients of human axillary lymph nodes and their use to generate parametric images of lymphoid tissue. 3D-OCT images were obtained from excised lymph nodes and optical attenuation coefficients were extracted assuming a single scattering model of OCT. We present the measured attenuation coefficients for several tissue regions in benign and reactive lymph nodes, as identified by histopathology. We show parametric images of the measured attenuation coefficients as well as segmented images of tissue type based on thresholding of the attenuation coefficient values. Comparison to histology demonstrates the enhancement of contrast in parametric images relative to OCT images. This enhancement is a step towards the use of OCT for in situ assessment of lymph nodes. PMID- 22312590 TI - Abundance and distribution of the highly iterated palindrome 1 (HIP1) among prokaryotes. AB - We have studied the abundance and phylogenetic distribution of the Highly Iterated Palindrome 1 (HIP1) among sequenced prokaryotic genomes. We show that an overrepresentation of HIP1 is exclusive of some lineages of cyanobacteria, and that this abundance was gained only once during evolution and was subsequently lost in the lineage leading to marine pico-cyanobacteria. We show that among cyanobacterial protein sequences with annotated Pfam domains, only OpcA (glucose 6-phosphate dehydrogenase assembly protein) has a phylogenetic distribution fully matching HIP1 abundance, suggesting a functional relationship; we also show that DAM methylase (an enzyme that has the four central nucleotides of HIP1 as is site of action) is present in all cyanobacterial genomes (independently of their HIP1 content) with the exception of marine pico-cyanobacteria whom might have lost this enzyme during the process of genome reduction. Our analyses also show that in some prokaryotic lineages (particularly in those species with large genomes), HIP1 is unevenly distributed between coding and non-coding DNA (being more common in coding regions; with the exception of Cyanobacteria Yellowstone B' and Synechococcus elongates where the reverse pattern is true). Finally, we explore the hypothesis that the HIP1 can be used as a molecular "water-mark" to identify horizontally transferred genes from cyanobacteria to other species. PMID- 22312591 TI - Tropical Africa as a cradle for horizontal transfers of transposable elements between species of the genera Drosophila and Zaprionus. AB - We have recently reported numerous cases of horizontal transfers of transposable elements between species of drosophilids. These studies revealed a substantial number of horizontal transfers between species of the subgroup melanogaster of the genus Drosophila and between these species and species of the genus Zaprionus. In this review, these transfers and similar, previously reported events are discussed and reanalysed to portray the interrelationships between the species that allowed the occurrence of so many horizontal transfers. The paper also addresses problems that may arise in drawing inferences about the time period during which the horizontal transfers occurred and the factors that may be associated with these transfers are discussed. PMID- 22312592 TI - Alignment-free detection of horizontal gene transfer between closely related bacterial genomes. AB - Bacterial epidemics are often caused by strains that have acquired their increased virulence through horizontal gene transfer. Due to this association with disease, the detection of horizontal gene transfer continues to receive attention from microbiologists and bioinformaticians alike. Most software for detecting transfer events is based on alignments of sets of genes or of entire genomes. But despite great advances in the design of algorithms and computer programs, genome alignment remains computationally challenging. We have therefore developed an alignment-free algorithm for rapidly detecting horizontal gene transfer between closely related bacterial genomes. Our implementation of this algorithm is called alfy for "ALignment Free local homologY" and is freely available from http://guanine.evolbio.mpg.de/alfy/. In this comment we demonstrate the application of alfy to the genomes of Staphylococcus aureus. We also argue that-contrary to popular belief and in spite of increasing computer speed-algorithmic optimization is becoming more, not less, important if genome data continues to accumulate at the present rate. PMID- 22312593 TI - Plasmid segregation without partition. AB - Low-copy number plasmids need a segregation mechanism to assort one half of the plasmid copies to each daughter cell during cell division. This can be achieved directly by partitioning plasmid copies through a mechanism reminiscent of eukaryotic mitosis. Briefly, plasmid copies are paired around a centromere-like site, and then separated toward the daughter cells at cell division. Partition mechanisms are used by a majority of well-studied plasmids. They involve two proteins, a DNA-binding protein and a motor protein, besides the centromeric site. However, some plasmids do not encode typical partition systems, so alternative segregation mechanisms must be considered. For instance, chromosome segregation could provide the driving force for plasmid movement, through a "pilot-fish"-like mechanism. In support of this assumption, we recently demonstrated that plasmid R388 segregation, which does not involve a plasmid encoded motor protein, requires a single plasmid-encoded DNA-binding protein. Besides, the new segregation system becomes essential when the plasmid encodes conjugation machinery, providing a new understanding of how plasmids integrate conjugative transfer with segregation. PMID- 22312594 TI - Tracing common origins of Genomic Islands in prokaryotes based on genome signature analyses. AB - Horizontal gene transfer constitutes a powerful and innovative force in evolution, but often little is known about the actual origins of transferred genes. Sequence alignments are generally of limited use in tracking the original donor, since still only a small fraction of the total genetic diversity is thought to be uncovered. Alternatively, approaches based on similarities in the genome specific relative oligonucleotide frequencies do not require alignments. Even though the exact origins of horizontally transferred genes may still not be established using these compositional analyses, it does suggest that compositionally very similar regions are likely to have had a common origin. These analyses have shown that up to a third of large acquired gene clusters that reside in the same genome are compositionally very similar, indicative of a shared origin. This brings us closer to uncovering the original donors of horizontally transferred genes, and could help in elucidating possible regulatory interactions between previously unlinked sequences. PMID- 22312595 TI - [Family relatives of persons with borderline personality disorder: a pre experimental study of a group intervention]. AB - The present study evaluates a standardized group intervention for individuals with a family relative diagnosed with Borderline Personality Disorder (BPD) or suffering from severe emotional disregulation, impulsive behavior, and interpersonal conflict, as reported by the participants of the study. This study is a preliminary exploratory step toward a future efficacy study. The intervention is based on Dialectical Behavioral Therapy and is structured as a 12 week program that introduces participants to psychoeducation, therapeutic strategies and training skills. An analysis of the degree of caretaker burden and psychological distress among participants was conducted in two phases: before and after the 12-week program. In the first phase, descriptive statistics present a sample of family relatives (n = 42) with a high degree of caretaker burden and intense psychological distress. There were significantly higher rates of burden, distress, and family conflict among the subjects whose family relatives had previous suicide attempts and hospitalizations. Subjects who completed the intervention experienced a reduction in level of burden, psychological distress and somatic symptoms. The findings are useful for designing group interventions for relatives of individuals with borderline personality disorder, and efficacy studies to evaluate them. More is discussed on the psychological factors to be considered for experimental research in this population. PMID- 22312596 TI - [Diagnosis and treatment of child and adolescent depression]. AB - The present paper reviews the available literature on the current state of knowledge regarding depression in children and adolescents. Empirically supported psychotherapeutic treatment adjustments for children are described, such as the Self-Control Therapy (CBT), Penn Prevention Program; and other treatments that are experimental phase. Similarly empirically supported psychotherapeutic treatment adjustments for adolescents are described, such as Adolescent Coping with Depression, Interpersonal Psychotherapy; and other treatments that are experimental phase as Biblotherapy and Attachment-Based Family Therapy. PMID- 22312597 TI - [Negative symptoms in patients with non schizophrenic psychiatric disorders]. AB - INTRODUCTION: The presence of negative symptoms (NS) in different clinical entities other than schizophrenia, with a dimensional approach of negative symptoms, was considered in this work. OBJECTIVES: Determine the presence and distribution of NS, in a population of patients with non schizophrenic psychiatric disorders attending ambulatory treatment at public hospitals. METHODS: Patients with define DSM IV diagnosis criteria for different disorders; affective, alimentary, substance abuse, anxiety, personality disorders and patients with ILAE diagnoses criteria for temporal lobe epilepsy were included. All patients underwent the subscale PANNS for negative symptoms of schizophrenia. Student T test was calculated to determine the differences of frequency for NS among psychiatric disorders. RESULTS: 106 patients were included; 60 women, 46 men, 38 years +/- 12.1. The 90% of patients have a low score of NS. Media 11.6, Max/min 9.38 -14.29. Emotional withdrawal and passive social withdrawal were more frequent in alimentary disorders than in affective disorder and than in epilepsy. Emotional withdrawal was more frequent in substance disorders than epilepsy. CONCLUSIONS: According this study, negative symptoms are present in a low to moderate intensity in non schizophrenic psychiatry entities and in the temporal lobe epilepsy. PMID- 22312598 TI - [Positivism in Argentina and its scope in Latin America]. AB - In this paper the historical-epistemological statute of nineteenth-century European positivism is discussed to further develop its scope in the constitution of Science in general and in the conformation of the disciplines tied to the human behavior in the time of the creation of the nation's institutions in Argentina. The ideological bias that this thinking legitimates in key moments of identity construction, such as the Centenary period, is analyzed. Finally, emphasis is made on the incidence of positivism in other countries in the region observing in every case the same ideological bias found in the Argentinean case, tinged by cultural and socio-political variables. PMID- 22312599 TI - [Evolution and situation of the historiography of psychiatry in Argentina]. AB - Historical researches focusing on the study of the ideas on madness and on psychiatry as a medical specialty in Argentina published until 1980 were few, and they were scattered throughout a time period covering more than a century. Some of them, however, constituted sources of useful data that contributed to subsequent developments which are still, in great measure, under way. New collective projects adopting new methodological approaches to address the subject have emerged in recent years. In this respect, the establishment of a vast plan for the research and compilation of primary sources, the organization and development of a formation of human resources that may adequately meet future research work, and a more solid assurance of the publication and divulgement of this research work are still pending. This article, of an introductory nature and predominantly descriptive and panoramic, reviews the main works and authors and their theoretical conceptions, situating them in the context of their time. PMID- 22312600 TI - [The evolution of psychiatry in Uruguay]. AB - Uruguay, a country in South America situated between Brazil and Argentina, has a population of 3 million, a literacy rate of 97%, and health coverage of 87% . Treatment of patients with mental disturbances has existed throughout its history. From colonial times and in the Spanish religious tradition, treatment of mental alienation had recourse to the "madhouse" of the Charity Hospital in Montevideo (1788). Half a century after independence the National Lunatic Asylum was built (1880), and the field of psychiatry began to develop, centred on the asylum-hospital. Within a French medical heritage, institutions such as the Chair of Psychiatry (1907) and the Society of Psychiatry (1923) were created; their academic activities permanently invigorated the growth of this branch of medicine. Since the late 1960's, with the contribution of both European thought and the North American influence, psychiatry has begun a progressive transformation, with positive gains (extension of psychiatry to the whole country, more pragmatic treatments with community involvement, academic links with non-public institutions, integration between models, etc.), but also with negative aspects (an increasing risk of abandoning the discipline of psychopathology and of trivialising diagnosis and therapy). PMID- 22312601 TI - [History of psychiatric service in Brazil: the case of Colonia Juliano Moreira (1940-1954)]. AB - The article analyzes the history of Colonia Juliano Moreira (Juliano Moreira Colony) during the 1940s and early 1950s, in order to understand the relationship between mental health services and Brazilian national health policy at that time. Charts, newsletters, and medical reports of the institution are used as primary sources, as well as official documents issued by the office then in charge of psychiatric service, the Servico Nacional de Doencas Mentais do Ministerio da Educacao e Saude (Mental Disease National Service, under the Ministry of Education and Health). It observes how Colonia Juliano Moreira, created in 1924 as an agricultural colony, and based on praxitherapy as well as family therapy methods, has undergone an expansion of its physical and assistance resources within the Brazilian psychiatric health policy. PMID- 22312602 TI - [A state without memory. The ideological abolition of the insane asylum in Mexico (1945-1968)]. AB - The present article analyzes a campaign by the Mexican government, among the public and the medical profession, to disseminate a health care reform that culminated with the opening of thirteen Farms for the mentally ill and the ideological abolition of the insane asylum in the sixties of the twentieth century. To do this, renowned psychiatrists who held public positions built a black legend over the most emblematic insane asylum of the country, pointing out as the main cause of failure the constraint to which patients were subjected. In doing so, they resembled the mental hospital to a prison and the insane to a social threat, because they reduced that institution's function and denied the many experiences that would ?t in it: a place of confinement and refuge, a therapeutic and knowledge production space. Even though Mexican psychiatry was professionalized in the space of the asylum, the State wanted to erase the memory of that past to suggest the establishment of a new era in mental health, where the patients would no longer be subject to any restrictions which could curtail their freedom. Overcoming the asylum model meant creating "open door" therapeutic alternatives, but the decision was to distort the past to exalt the future. PMID- 22312603 TI - The hidden cause of dysphagia--epiphrenic diverticulum and esophageal motility disorders. PMID- 22312604 TI - An era of safety culture. PMID- 22312605 TI - Indicators of safety compromise in gastrointestinal endoscopy. AB - INTRODUCTION: The importance of quality indicators has become increasingly recognized in gastrointestinal endoscopy. Patient safety requires the identification and monitoring of occurrences associated with harm or the potential for harm. The identification of relevant indicators of safety compromise is, therefore, a critical element that is key to the effective implementation of endoscopy quality improvement programs. OBJECTIVE: To identify key indicators of safety compromise in gastrointestinal endoscopy. METHODS: The Canadian Association of Gastroenterology Safety and Quality Indicators in Endoscopy Consensus Group was formed to address issues of quality in endoscopy. A subcommittee was formed to identify key safety indicators. A systematic literature review was undertaken, and articles pertinent to safety in endoscopy were identified and reviewed. All complications and measures used to document safety were recorded. From this, a preliminary list of 16 indicators was compiled and presented to the 35-person consensus group during a three-day meeting. A revised list of 20 items was subsequently put to the consensus group for vote for inclusion on the final list of safety indicators. Items were retained only if the consensus group highly agreed on their importance. RESULTS: A total of 19 indicators of safety compromise were retained and grouped into the three following categories: medication-related - the need for CPR, use of reversal agents, hypoxia, hypotension, hypertension, sedation doses in patients older than 70 years of age, allergic reactions and laryngospasm/bronchospasm; procedure related early - perforation, immediate postpolypectomy bleeding, need for hospital admission or transfer to emergency department from the gastroenterology unit, instrument impaction, severe persistent abdominal pain requiring evaluation proven to not be perforation; and procedure-related delayed - death within 30 days of procedure, 14-day unplanned hospitalization, 14-day unplanned contact with a health provider, gastrointestinal bleeding within 14 days of procedure, infection or symptomatic metabolic complications. CONCLUSIONS: The 19 indicators of safety compromise in endoscopy, identified by a rigorous, evidence-based consensus process, provide clear outcomes to be recorded by all facilities as part of their continuing quality improvement programs. PMID- 22312606 TI - Awareness of postpolypectomy surveillance guidelines: a nationwide survey of colonoscopists in Canada. AB - INTRODUCTION: Due to the increasing demand for colonoscopy, adherence to postpolypectomy surveillance guidelines is important. Suboptimal compliance can lead to unnecessary risks and ineffective use of resources. OBJECTIVE: To determine the awareness of and adherence to postpolypectomy surveillance guidelines among members of the Canadian Association of Gastroenterology (CAG). METHODS: A survey describing 14 clinical cases was mailed to all physician members (n=411) of the CAG. Respondents were required to recommend a surveillance interval and a reason for his or her choice. RESULTS: A total of 150 colonoscopists (37%) completed the survey. Adherence to the guidelines varied from 23% to 96% per clinical scenario (median 63%). Recommended surveillance intervals were too short in 0% to 60% of the different cases (median 8%). The recommended interval was most often (60%) too short for a patient with one tubular adenoma with high-grade dysplasia. Surveillance intervals were too long in 4% to 75% of the cases (median 9%). The recommended interval was most often too long in a patient with a villous adenoma 15 mm in size and removed piecemeal (75%). Most often, recommendations were reported to be based on guidelines (median 74%; range 31% to 94%). However, in nine of 14 cases, more than 10% (median 18%; range 12% to 38%) of the respondents stated that their recommendation was based on guidelines, but did not provide the appropriate surveillance interval. CONCLUSIONS: Compliance to colonoscopy surveillance guidelines is suboptimal and reflects both overuse and underuse. The results show that awareness about the content of guidelines needs to be raised and strategies implemented to increase adherence. PMID- 22312607 TI - Antibiotic prophylaxis in transarterial therapy of hepatocellular carcinoma: a meta-analysis. AB - BACKGROUND: The use of prophylactic antibiotics against postprocedure infection in patients undergoing transarterial therapy for hepatocellular carcinoma is controversial. AIM: To compare the effects of prophylactic antibiotic treatment and no prophylactic antibiotic treatment on infectious complications following transarterial procedures. METHODS: Clinical trials fulfilling predefined selection criteria were identified by searching several bibliographic databases; a meta-analysis was performed where appropriate. RESULTS: Four trials of inadequate quality consisting of 210 patients were included in the analysis. Only one case of possible postprocedure infection in each group was reported. The rate of patients developing fever (RR 0.91 [95% CI 0.61 to 1.35]), changes in peripheral white blood cell count or serum C-reactive protein levels, and the mean length of hospital stay (mean difference 0.20 [95% CI 0.75 to 1.14]) showed no significant intergroup differences between antibiotic and no antibiotic treatment. Furthermore, the results of the present study indicated that the incidence of bacteremia, septicemia, sepsis or hepatic abscess after transarterial therapy was rare. CONCLUSION: Antibiotic prophylaxis in patients undergoing transarterial therapy for hepatocellular carcinoma may not be routinely necessary. However, a more judicious use of antibiotics is recommended for patients who are at an increased risk of infection. Nevertheless, prospective trials on a larger scale are clearly needed. PMID- 22312608 TI - Current considerations of direct percutaneous endoscopic jejunostomy. AB - BACKGROUOND: Direct percutaneous endoscopic jejunostomy (DPEJ) is a well-known approach to deliver postpyloric enteral nutritional support to individuals who cannot tolerate gastric feeding. However, it is technically difficult, and some case series have reported significant procedural failure rates. The present article describes current indications, successes and complications of DPEJ placement. METHODS: A MEDLINE database search was performed to identify relevant articles using the key words "direct percutaneous endoscopic jejunostomy", "percutaneous endoscopic gastrostomy", and "percutaneous endoscopic gastrostomy with a jejunal extension tube". Additional articles were identified by a manual search of the references cited in the key articles obtained in the primary search. RESULTS: DPEJ is gradually becoming more common in the treatment of patients who cannot tolerate gastric feeding. Differences in patient selection and technique modifications may contribute to the various success rates reported. Failure is most often due to inadequate transillumination or gastroduodenal obstruction. Currently, there are limited data to evaluate the safety and effectiveness of DPEJ. CONCLUSION: The clinical use of DPEJ is increasing. With appropriate care and expertise, DPEJ may prove to be reliable and safe. PMID- 22312610 TI - Is your practice truly patient-centric? PMID- 22312611 TI - Derm emergencies: detecting early signs of trouble. AB - Life-threatening dermatologic conditions do not always present with classic findings. This review--and the accompanying images--will help you recognize and respond to them without delay. PMID- 22312609 TI - Helicobacter pylori in First Nations and recent immigrant populations in Canada. AB - The diminishing prevalence of Helicobacter pylori infection among most segments of the Canadian population has led to changes in the etiologies and patterns of associated upper gastrointestinal diseases, including fewer peptic ulcers and their complications. Canadian Aboriginals and recent immigrants are among populations in which the prevalence of H pylori infection remains high and, therefore, the health risks imposed by H pylori remain a significant concern. Population-based strategies for H pylori eradication in groups with a low prevalence of infection are unlikely to be cost effective, but such measures are attractive in groups in which the prevalence rates of infection remain substantial. In addition to a lower prevalence of peptic ulcers and dyspepsia, the public health value of eradication may be particularly important if this leads to a reduction in the prevalence of gastric cancer in high prevalence groups. Therefore The Canadian Helicobacter Study Group held a conference that brought together experts in the field to address these issues, the results of which are reviewed in the present article. Canadians with the highest prevalence of H pylori infection are an appropriate focus for considering the health advantages of eradicating persistent infection. In Canadian communities with a high prevalence of both H pylori and gastric cancer, there remains an opportunity to test the hypothesis that H pylori infection is a treatable risk factor for malignancy. PMID- 22312612 TI - Infertility: help for couples starts with you. AB - A patient tells you she's "starting to worry" that getting pregnant won't be as easy as she'd hoped. Before you provide a referral, look for clues in the couple's histories. PMID- 22312613 TI - Combatting the cough that won't quit. AB - By the time patients come to see you, they've often tried a host of OTC remedies. This review and handy algorithm will help you detect and treat the cause of persistent cough without delay. PMID- 22312614 TI - PURLs: would this long-acting bronchodilator be better for your patient? AB - Tiotropium outperformed salmeterol in reducing the frequency of exacerbations in patients with moderate-to-severe COPD. PMID- 22312615 TI - Erythematous patches on the hands. AB - Our patient's history of obsessive-compulsive disorder may have masked the true diagnosis for years. PMID- 22312616 TI - Clinical inquiry. Which drugs work best for early Parkinson's disease? AB - Levodopa/carbidopa is the most effective medical therapy for Parkinson's disease, but it's associated with dyskinesia. PMID- 22312617 TI - A mental health brief intervention in primary care: does it work? AB - An onsite adjunctive service appears to improve the care of patients with mental health disorders. PMID- 22312618 TI - The National Allergy Survey Assessing Limitations (NASAL): patient and health care professional perspectives in allergic rhinitis. PMID- 22312619 TI - Comorbidities and allergic rhinitis: not just a runny nose. AB - Allergic rhinitis is rarely found in isolation and should be considered in the context of upper and lower airway disease. People with AR are at greater risk of suffering asthma, rhinosinusitis, and other related upper airway conditions. Most people with both nasal allergies and asthma report that their asthma gets better when their nasal allergies are under control. People with AR are more than twice as likely to suffer problems sleeping due to their nasal allergy symptoms. PMID- 22312620 TI - Insights on allergic rhinitis from the patient perspective. AB - Although intranasal steroid sprays are the preferred treatment of the majority of health care providers, this opinion is not carried through to patient treatment. Approximately two-thirds of adults with nasal allergy symptoms report that they use over-the-counter, nonprescription medicines, and only one-third report that they use an intranasal steroid spray. Lack of familiarity and poor patient awareness are key barriers to intranasal steroid spray use. Dissatisfaction related to side effects among users of these medications leads some of those who are familiar with intranasal steroid sprays to discontinue use after it has been prescribed. Improved health care provider-patient communication and education is a vital step toward improving the long-term management of allergic rhinitis. PMID- 22312621 TI - Closing thoughts: implications of the findings from the National Allergy Survey Assessing Limitations for the management of allergic rhinitis in America. PMID- 22312622 TI - Allergic rhinitis substantially impacts patient quality of life: findings from the Nasal Allergy Survey Assessing Limitations. AB - People with allergic rhinitis rate their overall health significantly lower than individuals without nasal allergies. Compared with the general population, more people with AR complain of difficulty getting to sleep, waking up during the night, lack of a good night's sleep, or a combination of these, as a result of their nasal symptoms. More than half of individuals with AR describe their symptoms as impacting daily life a lot or to a moderate degree. More adults with AR report that their health limits them from doing well at work compared with adults without nasal allergies, and their estimated productivity drops by an average of 20% on days when their nasal symptoms are at their worst. PMID- 22312627 TI - Retraction notice to: Human health risk assessment from exposure to trihalomethanes in Canadian cities [Environment International 36 (2010) 453-460]. PMID- 22312628 TI - Building better bubbles. PMID- 22312629 TI - Three-dimensional genetics. PMID- 22312630 TI - Peering deeper into the transcriptome. PMID- 22312631 TI - The survival of the fittest. PMID- 22312632 TI - Organic chemistry expands imaging options. PMID- 22312633 TI - A handle on neurodegenerative disease complexity. PMID- 22312634 TI - Method of the Year 2011. PMID- 22312635 TI - The author file: Khalid Salaita. PMID- 22312636 TI - Points of view: Data exploration. PMID- 22312637 TI - Gene-editing nucleases. PMID- 22312638 TI - Primer: genome editing with engineered nucleases. PMID- 22312639 TI - Infectious diseases [2011:1]. PMID- 22312640 TI - Regulation failing to keep up with India's trials boom. PMID- 22312641 TI - NICE epilepsy guidance "may be detrimental to patient care". PMID- 22312642 TI - Cuts in Portugal's NHS could compromise care. PMID- 22312644 TI - News from the foundation for physical therapy. PMID- 22312643 TI - Charles Dickens, The Lancet, and Oliver Twist. PMID- 22312645 TI - The story of the heartbeat, I: part I-heart rate: the rhythm of life. PMID- 22312647 TI - Revista Espanola de Cardiologia. PMID- 22312646 TI - Heinrich Schelbert, an emigre in the land of opportunity. PMID- 22312648 TI - [To the Editors: The Hungarian Healthcare Society's assessment and recommendations for medical specialty education in Hungary]. PMID- 22312649 TI - Public-nonprofit partnership performance in a disaster context: the case of Haiti. AB - During disasters, partnerships between public and nonprofit organizations are vital to provide fast relief to affected communities. In this article, we develop a process model to support a performance evaluation of such intersectoral partnerships. The model includes input factors, organizational structures, outputs and the long-term outcomes of public-nonprofit partnerships. These factors derive from theory and a systematic literature review of emergency, public, nonprofit, and network research. To adapt the model to a disaster context, we conducted a case study that examines public and nonprofit organizations that partnered during the 2010 Haiti earthquake. The case study results show that communication, trust, and experience are the most important partnership inputs; the most prevalent governance structure of public-nonprofit partnerships is a lead organization network. Time and quality measures should be considered to assess partnership outputs, and community, network, and organizational actor perspectives must be taken into account when evaluating partnership outcomes. PMID- 22312650 TI - Voice and choice in health care in England: understanding citizen responses to dissatisfaction. AB - Using data from a five-year online survey the paper examines the effects of relative satisfaction with health services on individuals' voice-and-choice activity in the English public health care system. Voice is considered in three parts - individual voice (complaints), collective voice voting and participation (collective action). Exercising choice is seen in terms of complete exit (not using health care), internal exit (choosing another public service provider) and private exit (using private health care). The interaction of satisfaction and forms of voice and choice are analysed over time. Both voice and choice are correlated with dissatisfaction with those who are unhappy with the NHS more likely to privately voice and to plan to take up private health care. Those unable to choose private provision are likely to use private voice. These factors are not affected by items associated with social capital - indeed, being more trusting leads to lower voice activity. PMID- 22312651 TI - Esophageal stromal tumor. PMID- 22312652 TI - Brainteaser. Eosinophilic esophagitis. PMID- 22312653 TI - [Retirement of a reformer. interviewed by Hartmann Hinterhuber (interview by Patrick Bock)]. PMID- 22312654 TI - [Manipulation of nerve net with a high-frequency retrograde transport virus vector]. PMID- 22312655 TI - Investigating and managing pyrexia of unknown origin in adults. AB - Few clinical problems generate such a wide differential diagnosis as pyrexia (fever) of unknown origin. The initial definition proposed by Petersdorf and Beeson in 1961,1 later revised, is "a fever of 38.3 degrees C (101 degrees F) or more lasting for at least three weeks for which no cause can be identified after three days of investigation in hospital or after three or more outpatient visits." 2-4Essentially the term refers to a prolonged febrile illness without an obvious cause despite reasonable evaluation and diagnostic testing. A fever that is not self limiting for which no cause can be found can become a source of frustration for both patient and doctor. There is little consensus on how such patients should be investigated, although recent prospective studies have evaluated diagnostic protocols to suggest approaches to investigation. 356 We discuss evidence from epidemiological and diagnostic studies and suggest an approach to investigating and managing pyrexia of unknown origin. Immunocompromised individuals, those with HIV infection, and patients admitted to hospital for other reasons with persistent or unexplained fever represent distinct subgroups in which the likely causes, diagnosis, and treatment of pyrexia usually differ from those in patients who are not immunocompromised. We do not discuss these subgroups in this review other than to provide definitions of pyrexia of unknown origin in different groups of patients (see box 1). PMID- 22312656 TI - [Evaluation of therapy for schizophrenic patients with cognitive disorder]. PMID- 22312657 TI - A Chinese translation of Ambroise Pare's "Anatomy". PMID- 22312658 TI - A hearty meal? The prison diets of Cranmer and Latimer. PMID- 22312659 TI - Thomas Tymme and natural philosophy: Prophecy, alchemical theology, and the book of nature. PMID- 22312660 TI - Aleksandr Polezhaev and remembrance of war in the Caucasus: constructions of the soldier as victim. PMID- 22312661 TI - Body of the nation: mothering, prostitution, and women's place in post-Communist Latvia. PMID- 22312662 TI - [Keypoints in filling of a diaphragmatic defect]. PMID- 22312664 TI - A KISS for "meaningful use" of EMR: keep it simple stupid. PMID- 22312663 TI - Electronic health record (EHR) incentive payments. PMID- 22312665 TI - Preparing for the unwanted spotlight of a malpractice trial. PMID- 22312666 TI - Charting your HIT course--MSMS helps steer the way. PMID- 22312667 TI - What are some things I can begin doing this fall to prepare for the federal EHR incentives? PMID- 22312669 TI - HIT--what's in it for me? PMID- 22312668 TI - What is meaningful use? PMID- 22312670 TI - Vaccine information statement revised for rotavirus vaccines. PMID- 22312671 TI - Cyberbullying in the age of electronic technology. PMID- 22312672 TI - Who needs physicians anyway? PMID- 22312673 TI - [The genogram and the caring relationship]. PMID- 22312674 TI - [The drug reform is adopted by deputies]. PMID- 22312675 TI - [Prevention of care-induced pain]. PMID- 22312676 TI - [Electric stimulation or transcutaneous electrical nerve stimulation]. AB - Transcutaneous electrical nerve stimulation is a non-medicated therapy with no side effects, compatible with other treatments and able to be used for an unlimited time. It consists in emitting painless electrical pulses around the nerves or muscles, through electrodes placed on the skin and connected to an easy to-use generator or stimulator. PMID- 22312677 TI - [Insulin and meals, from carbohydrate counting to dose calculation]. AB - Adapting the insulin doses of type 1 diabetes patients to the amount of carbohydrates in their meals requires the personalised and individual link between carbohydrates and insulin for each meal to be established as well as the patient's active participation for an accurate carbohydrate estimate. The help and support provided by caregivers during the setting up of this new strategy must take into account patients' experience and expectations. PMID- 22312678 TI - [Training and information for freelance nurses, all life long]. AB - Nursing practice demands ever greater levels of skill, including from those providing home nursing care. A study was carried out, in 2008, within the French national institute for health and medical research (INSERM), in the context of a research master, to assess the differences in freelance nurses' approach to training and information research according to the type of practice (up to 2 nurses versus more than 2 nurses). The study shows that the method of practice influences the amount of work. The dynamics of formation is, in turn, lower for all nurses, mainly due to lack of time. PMID- 22312679 TI - [The mortuary room, the last place for care. Beyond the last breath]. PMID- 22312680 TI - [A new status for mortuaries]. AB - For a long time, hospital mortuaries were seen as the slightly shameful 'back offices' of institutions focusing primarily on medical successes. In recent years, the mortuary has come to be seen as a necessary facility for any modern hospital, subject to the same requirements of professionalism as other hospital departments, with staff who have an integral role to play in patient care. PMID- 22312681 TI - [Care in the mortuary: a duty of humanity]. AB - Caring for the dead and their loved ones is something human beings have always done. It acknowledges the deceased person's place as an individual within a social group. It begins with preparation of the corpse--the first stage of a religious or cultural rite. These rites are essential to separate the dead from the living and to allow the latter to mourn. PMID- 22312682 TI - [From the dead body management to the mortuary room care]. PMID- 22312683 TI - [The role of mortuary staff in dealing with families]. AB - The mortuary is a hospital department dealing with people who die in the hospital and providing support to their friends and family. It therefore provides continuity of care. From the moment the deceased person's body arrives at the mortuary to the point at which it leaves the hospital, mortuary staff prepare the deceased's body before it is presented to his/her loved ones, and contribute to medical and technical tasks (samples, autopsies, etc.) Training is required to ensure employees have the necessary skills for the job. PMID- 22312684 TI - [Ritual washing, another aspect of care]. AB - After death, mortuary staff attend to the deceased and his or her family until the deceased leaves the institution. Washing, dressing, presentation of the body and dealing with requests for information form part of this aspect of care. Religious practices, such as the ritual washing of the body may be requested by the family. As with all forms of care given to the deceased, staff facilitate the carrying out of such practices. PMID- 22312685 TI - [The mortuary: a place where lives can be saved]. AB - The mortuary is a hospital department dedicated to the care of patients who have died on-site. It is also a place of life and hope. Tissue samples (corneas, heart valves, etc.) may be taken there for people awaiting transplants. The final outcome will depend on respectful treatment of, and high-quality dialogue with, the deceased's family. PMID- 22312686 TI - [Training of mortuary staff: a shared approach to care]. AB - Mortuary staff are seeing a profound transformation in their profession. All of their duties (care for the deceased, support to families, other activities assigned to the mortuary) require training. Training is a legitimate aspiration for the caregivers concerned and is part of giving the profession the recognition it deserves. PMID- 22312687 TI - [Embalming: the living's final tribute to the deceased]. AB - There is more to an embalmer's job than the purely technical aspects. Embalmers are central to the crucial human relationship between the deceased, families and the professionals themselves. By making it easier for the living to face the dead, embalming allows mourning to start with as little trauma as possible, and gives the death and the deceased the dignity they deserve. PMID- 22312688 TI - [The mortuary: a place of life]. AB - The mortuary is a place where past, present and future converge. It is a place where families can prepare and find peace. Every day, mortuary staff offer humanity and care to the families and loved ones of the deceased, to help them continue to build their own lives. PMID- 22312690 TI - [The mortuary, the last place for care. Bibliography elements]. PMID- 22312689 TI - [Developing and promoting mortuaries]. PMID- 22312691 TI - [10/10 Global approach and tailored action plan to fight stress]. PMID- 22312692 TI - Chitosan-alginate nanocapsules for encapsulation of turmeric oil. AB - Turmeric oil is widely used in pharmaceutical and cosmetic applications because of its antibacterial, antifungal, antioxidant, and insect-repellent properties. However, turmeric oil is volatile, insoluble in water and unstable in certain environments, which causes difficulties with formulation development and stability of new products. One approach to overcome these problems is to encapsulate turmeric oil in carriers formed from naturally occurring polysaccharides. Among such polysaccharides, chitosan and alginate have been widely used as particulate carriers for encapsulation and controlled release of bioactive compounds. The potential for size reduction of the carriers to the nanometer scale is of particular interest for delivery systems. In this review, we provide an overview of the versatile properties of turmeric oil and discuss the use of alginate and chitosan for capsule formation and encapsulation of turmeric oil in chitosan-alginate nanocapsules. We also discuss the in vitro skin permeation of turmeric oil from nanocapsules. PMID- 22312693 TI - Determination of meglumine in pharmaceutical formulations using high performance liquid chromatography. AB - Four different approaches were followed for the development of a HPLC method for the determination of meglumine in solid dosage formulations: derivatization of meglumine prior to HPLC analysis, the use of an ion-pairing reagent in the mobile phase, the use of charged surface hybrid stationary phase and the use of a column designed for carbohydrate separations. The method using anionic pairing reagent in the mobile phase was shown to be suitable for the quantitative determination of meglumine in solid dosage forms. The HPLC separation was achieved on an Agilent Eclipse XDB-C18 column (150 mm x 4.6 mm, 3.5 microm particle size) using a mobile phase with octane-1-sulfonic acid. The method was validated and validation included the following studies: selectivity, precision (repeatability), linearity and accuracy. During validation experiments RID and DAD detectors were used. PMID- 22312694 TI - Simultaneous determination of evodiamine and rutecarpine in rabbit plasma by LC ESI-MS and its application to pharmacokinetics. AB - A sensitive and selective liquid chromatography-mass spectrometry (LC-MS) method for the determination of evodiamine and rutecarpine in rabbit plasma was developed and validated. The analytes and internal standard (IS) are extracted from plasma by one-step protein precipitation with acetonitrile, and separated on a Zorbax SB-C18 column (2.1 mm x 50 mm, 3.5 microm) using acetonitrile-0.1% formic acid as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode, and selective ion monitoring (SIM) mode used to quantify evodiamine and rutecarpine. The assay is linear over the range of 2-1600 ng/mL for evodiamine and rutecarpine, with a lower limit of quantification (LLOQ) of 5 ng/mL both for evodiamine and rutecarpine. Intra-day and inter-day precision are less than 12% and the accuracy are in the range of 90.9-104.3%. Furthermore, the newly developed method is successfully used for the determination of evodiamine and rutecarpine in rabbit plasma for pharmacokinetic study. PMID- 22312695 TI - Determination of bupropion and its main metabolite in rat plasma by LC-MS and its application to pharmacokinetics. AB - A sensitive and selective liquid chromatograpy-mass spectrometry method for the determination of bupropion and its main metabolite, hydroxubupropion, in rat plasma was developed and validated. After addition of carbamazepine as internal standard (IS) and precipitation of protein with acetonitrile, the plasma samples were analyzed on an Agilent Zorbax SB-C18 (2.1 mm x 50 mm, 3.5 microm) column at 30 degrees C, with acetonitrile-0.1% formic acid as mobile phase at a flow rate of 0.4 mL min(-1). The detection was carried out in the selective ion monitoring mode with a positive electrospray ionization interface. The calibration curve was linear over the 10-2000 ng mL(-1) for bupropion and 5-1000 ng mL(-1) for hydroxybupropion in plasma. RSD of inter-day and intra-day precision was less than 7% for bupropion, 9% for hydroxybupropion. The developed method was successfully applied to pharmacokinetic studies after single intragastric administration of bupropion 15 mg kg(-1) to rats. PMID- 22312696 TI - LC analysis of coumestrol incorporated into topical lipid nanoemulsions. AB - A simple, rapid, and sensitive LC method to determine coumestrol incorporated in the lipid nanoemulsions was validated. The analyses were performed at room temperature on a reversed-phase C18 column using a mobile phase composed of methanol/water with 0.1% trifluoracetic acid (70:30, v/v) at 0.8 mL min(-1). The detection was carried out on a UV detector at 343 nm. The linearity, in the range of 0.1-6.0 microg/mL, presented a determination coefficient (r2) of 0.999, calculated by the least square method. No interferences of the oil core or the gelling excipients were detected. The R.S.D. values for intra- and inter-day precision experiments were lower than 2%. The recovery ranged from 99.42% to 100.72%. Finally, the proposed method was successfully applied to determine coumestrol incorporated in the proposed topical formulations. PMID- 22312697 TI - Polymorphism of flucloxacillin sodium. AB - The polymorphism of flucloxacillin sodium has not been discussed sufficiently so far. Flucloxacillin sodium which was crystallized with different solvents, was found to exist in amorphism and three crystal forms (I, II, III). This results were confirmed by infra-red (IR) spectra, thermogravimetry (TG), X-ray diffraction analysis (XRD) and equilibrium solubility. It is noticed that form III has very good solubility in phosphate buffer solution, with an average solubility of 0.86 g (20-40 degrees C). However, more efforts are needed to carry out and decide whether this form can be used for industrial production. PMID- 22312698 TI - In vitro and in vivo evaluation of drug release from semisolid dosage forms. AB - This study presents the in vitro and in vivo testing of anti-inflammatory drug containing creams, hydrogels and organogels for dermal use. In vitro penetration studies were performed with products by measuring the diffused drug amount through synthetic membranes soaked in isopropyl myristate (IPM). Our developed preparations were investigated under in vitro conditions together with two marketed medicinal products used as reference preparations. In vivo studies were carried out on anaesthetized male Wistar rats; the carrageenan-induced paw oedema decreasing effect of twelve different formulations and the reference products were measured in comparison with a control group. All - previously in vitro screened - selected products reduced paw oedema in rats. Significant differences were found among the developed products both in vitro and in vivo. Correlation between the in vitro penetration studies and in vivo results were found in the case of o/w creams, organogels and hydrogels. PMID- 22312699 TI - Resveratrol nanosuspensions: interaction of preservatives with nanocrystal production. AB - The effect of six different preservatives on the production process and stability of resveratrol nanosuspensions was investigated. Nanosuspensions of the anti oxidant resveratrol were prepared by high pressure homogenization (1,500 bar, 20 homogenization cycles). The preservatives used were: caprylyl glycol (0.75%), Euxyl PE 9010 (1.0%), Hydrolite-5 (2.0), Phenonip (0.75%), Rokonsal PB-5 (0.5%) and MultiEx Naturotics (2.0%). Preservation is essential for oral and dermal nanosuspensions, but can impair the stability. The effect of the preservatives on stability as a function of cycle numbers was determined by size measurements (photon correlation spectroscopy (PCS), laser diffraction (LD) and light microscopy). Zeta potential measurements were performed for determination of the Stern potential (measurements in water) and as stability criterion (measurements in original dispersion medium), to elucidate the mechanism of destabilization. The preservatives could be placed into three groups. Hydrolite-5 did not affect the production process and the short term stability, sizes were practically identical to the preservative-free nanosuspension (e.g. PCS diameters 196 nm and 184 nm, respectively). All other preservatives impaired the stability medium to pronounced, being most pronounced for MultiEx Naturotics. Hydrolite-5 is recommended as preservative of choice. A mechanistic model was developed to explain the absence and the different degrees of destabilization. In general, when screening for suitable preservatives, suspensions are produced, different preservatives added and the size changes are monitored over long-term. The destabilizing effect of the preservatives on nanosuspensions became evident when added in the production process immediately, thus this can be used as a screening tool for optimal, non-destabilizing preservatives, replacing or minimizing time consuming long-term stability studies. PMID- 22312700 TI - Investigation of a new injectable thermosensitive hydrogel loading solid lipid nanoparticles. AB - For improving the effectiveness of cancer chemotherapy and avoiding rapid clearance of solid lipid nonoparticles (SLN) from the systemic circulation following systemic administration, 2-methoxyestradiol (2-ME) as model drug, PLGA PEG-PLGA as hydrogel material, an injectable SLN loaded hydrogel was developed. Integrity of SLN within and released from the hydrogel was confirmed by direct visualization by a scanning electron microscope (SEM), particle size measurement by laser light scattering, and free drug concentration in the release medium by ultracentrifugation. Moreover, in vitro release, thermo-sensitive properties and rheological behavior were investigated. The results indicated that SLN were stable in the hydrogel. In the release medium, most 2-ME existed in the SLN and intact 2-ME SLN could be released from the hydrogel for a prolonged period over 46 days. Their concentration showed a significant effect on the release rate, in contrast to particle size and pH value of the release medium. In addition, the SLN loaded hydrogel could still exhibit reversible thermo-sensitive properties and better syringeability. These results suggested that the SLN loaded hydrogel could transport SLN to the target site and control prolonged release of SLN, which may increase the efficacy of cancer chemotherapy. PMID- 22312701 TI - The influence of orifice height on flow rate of powder excipients. AB - The influence of the orifice height of a cylindrical, flat-bottomed hopper on the mass flow rate of the free-flowable size fractions of sodium chloride and boric acid was investigated. It was observed that a zone of sudden acceleration of the mass flow under gravity occurred when a critical orifice height had been achieved. Based on the results, an orifice diameter equal to 12 mm with a height of between 8-16 mm is recommended for the faster flow of sodium chloride while an orifice diameter equal to 8 mm with a height of less than 8mm is appropriate for the slower flow of boric acid. In summary, the orifice height should be taken into consideration as an important parameter of a cylindrical test hopper in order to obtain a reproducible and comparable mass flow as the single-point characteristic of powder flowability. PMID- 22312702 TI - Formulation of PEG-ylated L-asparaginase loaded poly (lactide-co-glycolide) nanoparticles: influence of Pegylation on enzyme loading, activity and in vitro release. AB - The present paper describes the advantage of PEG-ylation of L-asparaginase before encapsulation over its incorporation in the native form. During encapsulation a considerable amount of native protein undergoes denaturation and forms insoluble aggregates. In an effort to overcome this problem, L-asparaginase was PEG-ylated before subjecting it to the harsh conditions as encountered during double emulsion solvent evaporation technique. L-asparaginase was conjugated with succinimidyl succinate derivative of polyethylene glycol (SS-PEG, MW 5000) followed by characterization of the formed conjugate using size exclusion-HPLC and SDS PAGE. The PEG-ylated L-asparaginase consisted of different isomers from mono to multi PEG-ylated depending upon the number of Lysine residues (14 in case of L-asparaginase) with about 5% as native protein. The specific activity as retained after PEG-ylation was 62.84 +/- 8.2% and further about 82.7% of activity was recovered from the particles. Imitated studies with the native protein confirmed the enhanced stability of the conjugated protein when exposed to the organic solvent and sonication and showed comparatively less encapsulation efficiency due to increased hydrophilicity. Release profiles for native as well as conjugated proteins consisted of sustained release of about 66.66% and 44.45% in 28 days, respectively. The decrease in the release can be attributed to the increase in the molecular weight of the conjugated protein. The study finally proved that PEG-ylation protected the enzyme and prevented it from denaturation during encapsulation. PMID- 22312703 TI - Fluorofenidone suppresses epithelial-mesenchymal transition and the expression of connective tissue growth factor via inhibiting TGF-beta/Smads signaling in human proximal tubular epithelial cells. AB - OBJECTIVES: The present study was designed to investigate the potential effects and mechanism of fluorofenidone (AKF-PD) on transforming growth factor beta1 (TGF beta1)-induced tubular epithelial-mesenchymal transition (EMT) and the expression of connective tissue growth factor (CTGF) in human proximal tubular epithelial cells. METHODS: HK-2 cells were pretreated with AKF-PD, pirfenidone (PFD), Losartan, and SB431542 (an inhibitor of TGF-beta type I receptor). The pretreated HK-2 cells were subsequently co-treated with TGF-beta1 (5 ng/ml). The morphological changes of HK-2 cells were observed under an inverted microscope. Expression of alpha-SMA was detected by Western blot and immunofluorescence. The protein expression of ZO-1, fibronectin, CTGF, phosphorylated Smad2 (p-Smad2) and phosphorylated Smad3 (p-Smad3) were evaluated by Western blot. RESULTS: Through down-regulation of p-Smad2 and p-Smad3 proteins, AKF-PD significantly inhibited protein expression of alpha-SMA, fibronectin, and CTGF. Meanwhile, the depressed ZO-1 expression and morphological changes induced by TGF-beta1 were attenuated by AKF-PD. CONCLUSION: AKF-PD acts as an anti-fibrotic agent through blocking TGF beta/Smads signaling and consequently inhibits TGF-beta1-induced EMT and CTGF expression in human proximal tubular epithelial cells. PMID- 22312704 TI - Involvement of the calcium-sensing receptor in cyclosporin A-induced cardiomyocyte apoptosis in rats. AB - In this study, we sought to determine whether the calcium-sensing receptor (CaSR) is involved in Cyclosporin A (CsA)-induced cardiomyocyte apoptosis and identify its signal transduction pathway. Forty Wistar rats were randomly divided into four groups: the control group, the CsA group (CsA 15 mg/kg/day intraperitoneally, i.p.), the GdCl3 group (GdCI3 10 mg/kg, every other day, i.p.), and the CsA + GdCl3 group (CsA 15 mg/kg/day, i.p. and GdCl3 10 mg/kg, every other day, i.p.). The groups were treated for two weeks. Cardiomyocyte apoptosis and injury were observed by light microscopy, electron microscopy and TUNEL staining. CaSR mRNA expression was determined by RT-PCR, and CaSR protein expression was detected by western blot and immunohistochemistry. The protein expression levels of cytochrome c, cleaved caspase-9, cleaved caspase-3, Bax, and Bcl-2 were detected by western blot and immunohistochemistry. CsA increased the expression of CaSR mRNA and protein and enhanced cardiomyocyte apoptosis. GdCl3, a specific activator of CaSR, further enhanced CaSR expression and cardiomyocyte apoptosis and led to the upregulation of cytochrome c, cleaved caspase-9, cleaved caspase-3, and Bax, as well as the downregulation of Bcl-2. The present in vivo study provides further information on CsA-induced cardiomyocyte apoptosis. We determined for the first time that CaSR is involved in CsA-induced cardiomyocyte apoptosis in the rat through the activation of downstream cytochrome c-caspase-3 pathways. Furthermore, we offer evidence that the Bcl-2 family is involved in this process. These findings could provide novel strategies for the prevention and cure of CsA-induced cardiotoxicity. PMID- 22312705 TI - MiR-122 increases sensitivity of drug-resistant BEL-7402/5-FU cells to 5 fluorouracil via down-regulation of bcl-2 family proteins. AB - To investigate the changes in drug sensitivity of miR-122 transfected BEL-7402/5 FU cells. MiR-122 and negative miRNA expression vectors were constructed and stably transfected into BEL-7402/5-FU cells. Real-time RT-PCR was used to detect the level of miR-122, Bcl-XL, Bcl-2 and P53 mRNA. Western Blotting was used to detect Bcl-2, Bcl-XL and P53 protein expression. Drug sensitivity of the cells to 5-fluorouracil (5-FU) was analyzed with MTT and flow cytometry. Compared with negative miRNA transfectants or untreated cells, mRNA and protein expression level of Bcl-2, Bcl-XL in stable miR-122 transfectants were decreased. Accordingly, P53 protein expression showed a significant up-regulation; MTT results showed that after incubation with 5-FU, miR-122 transfectants had higher cell inhibitory rates than negative miRNA or untreated cells; flow cytometry results demonstrated that apoptosis rate increased in miR-122 transfected cells, compared with negative miRNA or untreated cells. After addition of 5-FU (10 and 100 micromol/I), miR-122 transfected cells showed higher apoptosis rate than negative miRNA or untreated cells. MiR-122 can specifically down-regulate the expression of Bcl-2 and Bcl-XL, and increase P53 activity in BEL-7402/5-FU cells, which increased cells spontaneous apoptosis and sensitize cells to 5-FU. Therefore, MiR-122 can be used as a potential therapy agent against human hepatoblastoma. PMID- 22312706 TI - Indole-3-carbinol and ultraviolet B induce apoptosis of human melanoma cells via down-regulation of MITF. AB - We investigated the mechanism of indole-3-carbinol (13C)/ultraviolet B (UVB) induced apoptosis using SK-MEL-2 and SK-MEL-5 human melanoma cells. 13C/UVB significantly reduced the viability of SK-MEL-2 cells, whereas it had little influence on SK-MEL-5 cells. Correspondingly, cell cycle analysis showed that 13C/UVB induced a clear increase in the sub-G0/G1 phase in SK-MEL-2 cells. Furthermore, 13C/UVB activated caspase-9, caspase-8, caspase-3, and Bid and caused the cleavage of poly(ADP-ribose) polymerase (PARP) in SK-MEL-2 cells. In contrast, 13C/UVB showed no effects on the apoptotic signaling pathways in SK-MEL 5 cells. Moreover, we found that 13C down-regulated the microphthalmia-associated transcription factor (MITF) in SK-MEL-2 cells, but not in SK-MEL-5 cells. Next, to investigate the involvement of MITF in 13C/UVB-induced apoptosis, MITF silencing was conducted using small interfering RNA (siRNA) for MITF in SK-MEL-5 cells. Interestingly, 13C/UVB dramatically decreased the viability of MITF-down regulated SK-MEL-5 cells. These results indicate that MITF plays a critical role in melanoma cell survival. PMID- 22312707 TI - Lipid-lowering effect of Rhus coriaria L. (sumac) fruit extract in hypercholesterolemic rats. AB - Hyperlipidemia is a major risk factor for development of atherosclerosis. In the present study, the hypolipidemic effects of sumac (Rhus coriaria L.) fruits in high cholesterold diet (HCD)-fed rats was investigated. There was a significant (p < 0.001) increase in the levels of total cholesterol (TC) and triglycerides (TG) along with augmented activities of serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase. Treatment with aqueous methanol extract of sumac fruits reduced the above alterations observed in hypercholesterolemic rats. Sumac extract also reversed the hypertrophic cardiac histology. Furthermore, in vivo toxicological studies showed no evidence of acute toxicity of the extract in male Wistar rats. In conclusion, sumac fruit extract intervention minimized the lipid abnormalities and abnormal biochemical changes induced in HCD fed rats. This shows that sumac fruit extract possesses cardioprotective and hepatoprotective activities which will be beneficial in hypercholesterolemic condition. PMID- 22312708 TI - Sibiralactone: a new monoterpene from Sibiraea angustata. AB - Sibiralactone (1), a new monoterpene derivative, was isolated from the leaves of Sibiraea angustata. The structure was determined by the analysis of its NMR data and the absolute configuration was established by TDDFT ECD calculation of the solution conformers. PMID- 22312709 TI - Bioconversion of proposed precursors into theobroxide and related compounds. AB - We have previously reported a tetraketide origin for theobroxide and its related compound. In the present study, bioconversion of natural and deuterium-labeled precursors of this proposed biosynthetic pathway by Lasiodipoldia theobromae was investigated. Theobroxide was quantified after bioconversion from each proposed precursor. The transformation of the isotopically labeled precursor to products was tracked by 2H NMR measurement. PMID- 22312710 TI - Microbial hydroxylation of S-(-)-perillyl alcohol by Fusarium heterosporium. AB - S-(-)-Perillyl alcohol (p-mentha-1, 8-diene-7-ol) (1) (500 mg) was converted by Fusarium heterosporium ATCC 15625 over 10 days at 25 degrees C to a new metabolite, 1,2-dihydroxyperillyl alcohol (p-mentha-8-en-1,2,7-triol) (3) in a yield of 13% (70 mg). The structure of 3 was established by IR and NMR spectroscopic, specific rotation, and mass spectral studies. PMID- 22312711 TI - A phytochemical investigation of Zanthoxylum setulosum. AB - The crude bark extract of Zanthoxylum setulosum from Monteverde, Costa Rica was notably cytotoxic (100% kill at 100 microg/mL) to MCF-7, MDA-MB-231, and MDA-MB 468 cells in vitro. Phytochemical studies of the bark extract revealed the triterpenoid lupeol, the lignan sesamin, the sesquiterpene sesquichamaenol, and the xanthone lichexanthone. This is the first report of the isolation of sesquichamaenol and lichexanthone from the bark extract of Z. setulosum. All structures were determined using NMR spectroscopic techniques (1H NMR and 13 degrees C NMR) and GC-MS and by comparison with literature data. Lupeol proved to be the cytotoxic component of Z. setulosum bark. PMID- 22312712 TI - Cytotoxic cembranoids from the Red Sea soft coral Sarcophyton glaucum. AB - One new cembrane diterpene, 2R,7R,8R-dihydroxydeepoxysarcophine (1), together with three known compounds, 7alpha,8beta-dihydroxydeepoxysarcophine (2), 7beta acetoxy-8alpha-hydroxydeepoxysarcophine (3), and sarcophine (4), have been isolated from the Red Sea soft coral Sarcophyton glaucum. Their structures were determined using 1D and 2D NMR spectroscopy. 7beta-Acetoxy-8alpha hydroxydeepoxysarcophine (3) exhibits cytotoxic activity against HepG2, HCT-116, and HeLa cells with IC50 values of 3.6, 2.3, and 6.7 microg/mL, respectively. PMID- 22312713 TI - C-lactam derivatives of oleanolic acid. The synthesis of C-lactam by Beckmann rearrangement of C-oxime. AB - Oleanolic acid, one of the most known triterpenes, was subjected to different chemical transformations within C-3 beta-hydroxyl group, a double bond between C 12 and C-13, and a carboxyl function at C-17 in order to obtain new derivatives. The key compound consists of four six-membered rings (A, B, D, E) and one enlarged ring (C ring) containing a nitrogen atom and a carbonyl function - lactam. This type of derivative can be obtained by Beckmann rearrangement of the appropriate oxime. The lactam can be transformed into thiolactam with the use of Lavesson's reagent. The method is also presented for new derivatives synthesis, as well as their structure elucidation by spectroscopic means. PMID- 22312714 TI - Analysis of native carotenoid composition of sweet bell peppers by serially coupled C30 columns. AB - Serial coupled columns reversed-phase separations in high-performance liquid chromatography can be a useful tool for the analysis of complex real samples. The great difficulties found when analyzing complex carotenoid samples, due to the high natural variability of these compounds, as well as to the presence of carotenoid esters, are well documented. In the present contribution, the applicability of connecting two C30 columns to increase significantly the separation power, resolution and peak capacity for the analysis of carotenoids in a complex carotenoid sample, like sweet bell peppers, has been shown for the first time. By using LC coupled to PDA/APCI-MS detectors, 56 different carotenoids have been detected in red sweet bell peppers. By using two serial coupled C30 columns a peak capacity of 95.4 was obtained, compared with 73 achieved using a single column. Moreover, resolution greatly improved between different critical peaks when using two serial coupled C30 columns, compared with a single column. Interestingly, free carotenoids, mono-esters and diesters were quantitatively equally represented (around 33% for each different class) in red sweet bell pepper, showing, therefore, a value for the ratio of mono esters/diesters of around 1, which could be considered a parameter of typicality. Free beta-carotene (12.6%), capsanthin-C14:0 (8.4%), and capsanthin-C12:0-C14:0 (8.9%) were the most abundant carotenoids in the three different classes of red sweet bell pepper. No carotenoid esters were detected in either yellow or green sweet bell peppers. The application of such methodology in the analysis of other complex carotenoid matrices could be a future objective of research. PMID- 22312715 TI - New antifungal cholestane and aldehyde derivatives from the red alga Laurencia papillosa. AB - The chloroform/methanol extract of the red alga, Laurencia papillosa, collected from the Red Sea in Saudi Arabia, was found to contain two cholestane derivatives: 3alpha, 6alpha-dihydroxy-5beta-cholestan-12-one (1) and the known, 6beta-hydroxycholest-4-en-3-one (2), which was isolated separately in a pure form for the first time. In addition to these compounds, a new aldehyde derivative, (E)-2-{(E) tridec-2-en-2-yl} heptadec-2-enal (3), was isolated. The structures of all compounds were established based on extensive spectroscopic (1D and 2D NMR, UV, IR) and mass spectrometric studies. All compounds, except 2, were tested for their antifungal activity. Significant activities were associated with 1 and 3 against Candida albicans, Aspergillus fumigatus, and A. flavus. PMID- 22312716 TI - Steroidal saponins from the fruits of Cestrum ruizteranianum. AB - Seven spirostane and furostane-type glycosides were isolated from the aqueous methanolic extract of the fruits of Cestrum ruizteranianum and characterized mainly by 2D NMR spectroscopy and mass spectrometry. These known saponins belong to the delta5-spirostene and delta5-furostene series and are reported in this species for the first time. PMID- 22312717 TI - Isolation and cholinesterase activity of Amaryllidaceae alkaloids from Nerine bowdenii. AB - Amaryllidaceae species are known as ornamental plants. Some contain galanthamine, an acetylcholinesterase inhibitor. The chemical composition of the alkaloid extract of bulbs of Nerine bowdenii Watson has been analyzed by means of GC/MS. Twenty-two compounds were detected and nineteen of them identified, one of which was belladine. The alkaloid extract showed promising cholinesterase inhibitory activities against human blood acetylcholinesterase (HuAChE; IC50 = 87.9 +/- 3.5 microg/mL) and human plasma butyrylcholinesterase (HuBuChE; IC50 = 14.8 +/- 1.1 microg/mL). Belladine inhibited HuAChE and HuBuChE in a dose-dependent manner with IC50 values of 781 +/- 12.5 microM and 284.8 +/-4.2 microM, respectively. PMID- 22312718 TI - HPLC determination of majdine in Vinca herbacea. AB - A reliable HPLC method coupled with DAD detection was developed and validated for determination of majdine in Vinca herbacea. The chromatographic separation was carried out on a Symmetry C18 column (250 mm x 4.6 mm, 5 microm, Waters) with an isocratic solvent system of 25 mM potassium phosphate buffer (pH = 3.0) acetonitrile. UV detection was performed at 225 nm. Good linear behavior over the investigated concentration range was observed with the value of r2 > 0.9978. The method was reproducible with intra- and inter-day variations of less than 4.38%. The proposed method was linear, accurate, precise and specific. The validated method was successfully applied to quantify majdine in various parts of V. herbacea, which was collected during the flowering months of April and May. The results indicated that the developed HPLC method could be used for the quality control of V. herbacea and for the standardization of its extracts in majdine. PMID- 22312719 TI - Pyridine metabolism and trigonelline synthesis in leaves of the mangrove legume trees Derris indica (Millettia pinnata) and Caesalpinia crista. AB - The aim of this study was to reveal the pyridine metabolism in leaves of two mangrove legumes, Derris indica (= Millettia pinnata or Pongamia pinnata) and Caesalpinia crista. Radioactivity from [carbonyl-14C]nicotinamide supplied exogenously to young leaf disks was recovered in nicotinic acid, nicotinic acid mononucleotide, NAD, NADP, nicotinamide mononucleotide and trigonelline. These mangrove species, especially D. indica, have strong ability to convert nicotinamide to trigonelline, but not to nicotinic acid glucoside. The endogenous trigonelline content in leaves of D. indica was more than 830 microg/g dry weight. This value is 5-12 times greater than that in leaves of Glycine max. There was little short-term effect of 250 and 500 mM NaCl (equivalent to ca. 50% and 100% sea water) on nicotinamide metabolism. PMID- 22312720 TI - Anti-adipogenic activity of Cordyceps militaris in 3T3-L1 cells. AB - Inhibition of adipocytes differentiation is suggested to be an important strategy for prevention and/or treatment of obesity. In our present study, Cordyceps militaris showed significant inhibitory activity on adipocyte differentiation in 3T3-L1 preadipocytes as assessed by measuring fat accumulation using Oil Red O staining. Activity-guided fractionation led to the isolation of cordycepin (1), guanosine (2) and tryptophan (3) as active compounds. All the three compounds were more effective in the prevention of early stage of adipogenesis than in lipolysis. In addition, combinational treatment of three compounds significantly increased anti-adipogenic activity. PMID- 22312721 TI - Two new cyclopeptides and one new nonenolide from Xylaria sp. 101. AB - Two novel cyclopeptides, xylarotides A (1), and B (2), and one novel nonenolide, xylarolide (3), along with two known compounds, coriloxin (4), and 2-hydroxy-3 methoxy-5-methyl-p-benzoquinone (5) were isolated from the fungal strain Xylaria sp. 101. This strain was isolated from the fruiting body of Xylaria sp. collected in Gaoligong Mountain, Yunnan Province. The chemical structures were elucidated by spectroscopic analyses, including 1D- and 2D-NMR spectroscopic experiments, and on the basis of HR-Q-TOF mass spectrometry. Antibacterial assays of 1 - 3 were carried out; no effects on the growth of the tested bacteria and yeast were observed. PMID- 22312722 TI - A novel flavonoid and furoquinoline alkaloids from Vepris glomerata and their antioxidant activity. AB - The dichloromethane extract of the aerial part of the plant Vepris glomerata (Rutaceae) yielded a new flavonoid, which was accorded the trivial name veprisinol (1), together with four known furoquinoline alkaloids: haplopine-3,3' dimethylallyl ether (2), anhydroevoxine (3), evoxine (4) and skimmianine (5). The structures of the compounds were established by 1D and 2D NMR spectroscopy, as well as HREIMS. Compounds 1 and 2 have strong antioxidant potential, similar to and in some instances better than ascorbic acid and can be used as beneficial additives to antioxidant supplements. PMID- 22312723 TI - Flavonoid constituents and free radical scavenging activity of Alchemilla mollis. AB - Antioxidant capacity of the methanolic extract of Alchemilla mollis was measured by its ability to scavenge the DPPH radical. The EtOAc fraction obtained after partition of the total extract was found to be the most active radical scavenger (IC50 9.8 +/- 1.8 microg/mL) and was subjected to fractionation by Sephadex LH-20 CC. Further purification by RP-18 CC led to the isolation of eight flavonoid glycosides: cis- and trans-tiliroside (1 and 2), rhodiolgin (3), hyperoside (4), isoquercitrin (5), miquelianin (6), sinocrassoside D2 (7), and gossypetin-3-O beta-D-galactopyranosyl-7-O-alpha-L-rhamnopyranoside (8). It was found that 8 is a new compound and its antioxidant activity is also reported. Identification of the isolated compounds was carried out by spectroscopic and spectrometric analysis (1D and 2D NMR, UV and MS). PMID- 22312724 TI - Ultrasound-assisted extraction of total phenols and flavonoids from dry tobacco (Nicotiana tabacum) leaves. AB - Yields of extracted substances, as well as total phenol and flavonoid compounds obtained by classical and ultrasonic extractions from dry leaves of two tobacco types (oriental and Virginia) by two different solvents (acetone and methanol) at two operating temperatures (25 and 40 degrees C) were compared. The yield of extractive, as well as total phenol and flavonoid compounds depended on the type of solvent, operational temperature and the tobacco type. The importance of these factors was assessed using 2(4) full factorial experiments without replication. PMID- 22312725 TI - Characterization of polyphenolic compounds in unripe chinotto (Citrus myrtifolia) fruit by HPLC/PDA/ESI/MS-MS. AB - The flavonoid and furocoumarin composition was investigated of peel and pulp tissues of unripe fruits of Citrus myrtifolia Rafinesque, an ingredient of the popular soft drink "chinotto". Compound separation and identification was made using an HPLC-PDA detector coupled to ESI/MS/MS in positive and negative mode. Eighteen compounds (3-hydroxy-3-methylglutaryl-, C- and O-glycosyl flavonoids, furocoumarins and polymethoxylated flavones) were identified and quantified. Data indicated that the overall amount of flavonoids and furocoumarins in peel was higher than in the pulp, even though their relative distribution did not significantly change, apart from a different distribution of flavones and a lower content of naringin in the peel. PMID- 22312726 TI - Bioactive compounds, RP-HPLC analysis of phenolics, and antioxidant activity of some Portuguese shrub species extracts. AB - In the ecosystem of Serra Da Estrela, some plant species have the potential to be used as raw material for extraction of bioactive products. The goal of this work was to determine the phenolic, flavonoid, tannin and alkaloid contents of the methanolic extracts of some shrubs (Echinospartum ibericum, Pterospartum tridentatum, Juniperus communis, Ruscus aculeatus, Rubus ulmifolius, Hakea sericea, Cytisus multiflorus, Crataegus monogyna, Erica arborea and Ipomoea acuminata), and then to correlate the phenolic compounds and flavonoids with the antioxidant activity of each extract. The Folin-Ciocalteu's method was used for the determination of total phenols, and tannins were then precipitated with polyvinylpolypyrrolidone (PVPP); a colorimetric method with aluminum chloride was used for the determination of flavonoids, and a Dragendorff's reagent method was used for total alkaloid estimation. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and beta-carotene bleaching tests were used to assess the antioxidant activity of extracts. The identification of phenolic compounds present in extracts was performed using RP-HPLC. A positive linear correlation between antioxidant activity index and total phenolic content of methanolic extracts was observed. The RP-HPLC procedure showed that the most common compounds were ferulic and ellagic acids and quercetin. Most of the studied shrubs have significant antioxidant properties that are probably due to the existence of phenolic compounds in the extracts. It is noteworthy to emphasize that for Echinospartum ibericum, Hakea sericea and Ipomoea acuminata, to the best of our knowledge, no phytochemical studies have been undertaken nor their use in traditional medicine been described. PMID- 22312727 TI - HPLC/PDA/ESI-MS evaluation of saffron (Crocus sativus L.) adulteration. AB - The present study evaluated the reliability of the ISO/TS 3632-2 UV-Vis spectrometric method for saffron classification, making experiments on saffron samples to which were added increasing concentrations of common saffron spice adulterants (safflower, marigold and turmeric). The results showed that the ISO/TS 3632-2 method is not able to detect addition of up to 10-20%, w/w, of saffron adulterants. For additions from 20 to 50%, w/w, of the three adulterants, saffron was classified in a wrong category; addition of higher than 50%, w/w, determined variations in the investigated parameters that did not allow identification of the product as "saffron". In all cases, the method did not permit the recognition of the nature of the adulterant. On the contrary, the specificity of the HPLC/PDA/MS technique allowed the unequivocal identification of adulterant characteristic marker molecules that could be recognized by the values of absorbance and mass. The selection of characteristic ions of each marker molecule has revealed concentrations of up to 5%, w/w, for safflower and marigold and up to 2% for turmeric. In addition, the high dyeing power of turmeric allowed the determination of 2%, w/w, addition using exclusively the HPLC/PDA technique. PMID- 22312728 TI - Ferric reducing, antiradical and beta-carotene bleaching activities of nicotinic acid and picolinic acid bioconjugates of curcumin. AB - Although curcumin displays several beneficial properties, its medicinal use is limited by its low bioavailability. In the present study we report the antioxidant potentials of two bioconjugates of curcumin with nicotinic acid and picolinic acid: di-O-nicotinoyl curcumin [1,7-bis (4-O nicotinoyl-3 methoxyphenyl)-1,6-heptadiene-3, 5-dione] and di-O-picolinoyl curcumin [1,7-bis (4-O-picolinoyl-3-methoxyphenyl)-1,6-heptadiene-3, 5-dione], in terms of ferric reducing, radical scavenging and beta-carotene bleaching abilities, and comparing the observed activity with that of curcumin. Results demonstrate that both the bioconjugates possess higher antioxidant potentials as evidenced by enhanced ferric reducing, radical scavenging and beta-carotene bleaching abilities, in comparison with curcumin. On the basis of our results we conclude that these bioconjugates of curcumin may be better than curcumin for medicinal and pharmacological applications. PMID- 22312729 TI - Antiviral activities of diarylheptanoids isolated from Alpinia officinarum against respiratory syncytial virus, poliovirus, measles virus, and herpes simplex virus type 1 in vitro. AB - Alpinia officinarum has been used as a folk medicine and contains diarylheptanoids that have various biological activities. However, their antiviral activities are less elucidated. We examined the antiviral activities of nine diarylheptanoids isolated from A. officinarum against respiratory syncytial virus (RSV), poliovirus, measles virus, and herpes simplex virus type 1 (HSV-1) using a plaque reduction assay. The 50% inhibitory concentrations of seven of the nine diarylheptanoids for RSV were moderately but significantly lower than their 50% cytotoxic concentrations, as determined by a trypan blue exclusion assay. Four diarylheptanoids with anti-RSV activity also showed anti-poliovirus and anti measles virus activities and three of the four exhibited anti-HSV-1 activity. Thus, seven of the nine diarylheptanoids examined exhibited potential antiviral activity against RSV, and most of the diarylheptanoids with anti-RSV activity, including two diarylheptanoids without anti-RSV activity, were effective against poliovirus, measles virus, and/or HSV-1 in vitro. Diarylheptanoids were suggested to have a broad spectrum of antiviral activity. PMID- 22312730 TI - Isolation of C-glycosyl xanthones from Coffea pseudozanguebariae and their location. AB - The biochemical composition of leaves from Coffea pseudozanguebariae, a wild caffeine-free coffee species, was determined. Two phenolic compounds were extracted from leaves, separated and characterized. Their structures were elucidated by mass spectrometry, and 1D and 2D NMR spectroscopy and were shown to be mangiferin (1) and isomangiferin (2), which were the main polyphenol products. Multiphoton fluorescence imaging was performed to visualize polyphenol distribution in leaf cross sections. Consistent biochemical analysis cell imaging techniques on leaves revealed yellow fluorescence in the epidermis and parenchyma cells corresponding to xanthone compounds. PMID- 22312731 TI - Antifungal activity and isomerization of octadecyl p-coumarates from Ipomoea carnea subsp. fistulosa. AB - Bioassay monitored HPLC assisted isolation and purification of the chief antifungal fraction of the leaves of Ipomoea carnea subsp. fistulosa (Convulvulaceae) were achieved using Colletotrichum gloeosporioides and Cladosporium cucumerinum as test organisms. The activity of the purified fraction was further confirmed by the dose dependent inhibition of the spore germination of Alternaria alternata and A. porri. The active fraction was identified as a mixture of (E)-octadecyl p-coumarate and (Z)-octadecyl p-coumarate. The two isomers were detected on an HPLC column with substantially different retention times, but once eluted from the column, one form was partly converted to the other in daylight. Conclusive evidence for the structures and their isomerization were obtained from the HPLC behavior, IR, UV, HRESIMS, CIMS and and NMR spectral data. Important 1H NMR and 13C NMR signals could be separately assigned for the isomers using 2D NMR techniques. PMID- 22312732 TI - New glucose esters from the fresh leaves of Jacaranda mimosaefolia. AB - From the fresh leaves of Jacaranda mimosaefolia were isolated Phytoquinoids 1-4 established as beta-D-glucopyranose 2-benzeneacetatel,6-bis(1-hydroxy-4-oxo-2,5 cyclohexadiene-1-acetate), for which the name Jacaranoside is proposed; beta-D glucopyranose 2-(4-hydroxybenzeneacetate) 1,6-bis(1-hydroxy-4-oxo-2,5 cyclohexadiene-1-acetate), for which the name Jacarandol is proposed; beta-D glucopyranose 2-benzeneacetate 1-(1-hydroxy-4-oxo-2,5-cyclohexadiene-1-acetate) and beta-D-glucopyranose 1,6-bis (1-hydroxy-4-oxo-2,5-cyclohexadiene-1-acetate) respectively. PMID- 22312733 TI - Shamiminol: a new aromatic glycoside from the stem bark of Bombax ceiba. AB - A new aromatic glycoside, shamiminol was isolated from the stem bark of Bombax ceiba along with the known constituents stigmasta-3,5-diene, lupenone, (+/-) lyoniresinol 2a-O-beta-D-glucopyranoside and opuntiol, obtained for the first time from this plant. The structure of shamiminol was elucidated on the basis of extensive 1D- and 2D-NMR spectroscopic and mass spectrometric studies as 3,4,5 trimethoxyphenol 1-O-beta-D-xylopyranosyl-(1 --> 2)-beta-D-glucopyranoside (1). PMID- 22312734 TI - Two new phenolic glycosides from Viburnum plicatum var. plicatum f. plicatum. AB - Two new glycosides, named dideoxyplicatumoside A (1) and erythro-syringylglycerol beta-O-4'-(+)-isoeucommin A 4'''-O-beta-D-glucopyranoside (2), together with seven known compounds, were isolated from the leaves of Viburnum plicatum Thunb. ex Murray var. plicatum f. plicatum. Their structures were established on the basis of NMR, MS and chemical data. PMID- 22312735 TI - Antimicrobial chemical constituents from the endophytic fungus Phomopsis sp. from Notobasis syriaca. AB - Phomosine K (1), a new phomosine derivative, has been isolated from Phomopsis sp., in addition to six known compounds: phomosine A (2), phenylalanine amide (3), 2-hydroxymethyl-4beta,5alpha,6beta-trihydroxycyclohex-2-en (4), (-) phyllostine (5), (+)-epiepoxydon (6), and (+)-epoxydon monoacetate (7). Preliminary studies showed that compound 1 had strong antibacterial activity, while compounds 4-7 showed good antifungal, antibacterial, and algicidal properties, except compounds 4 and 6, which lacked antifungal activity. PMID- 22312736 TI - Phomosines H-J, novel highly substituted biaryl ethers, isolated from the endophytic fungus Phomopsis sp. from Ligustrum vulgare. AB - From the endophytic fungus Phomosis sp., four known phomosines A-D (1-4) and three new phomosines H-J (5-7) have been isolated. The structures of the new compounds were determined on the basis of their spectroscopic data analysis (1H, 13C, 1H-1H COSY, HMQC, and HMBC NMR, as well as mass spectrometry). The structures of phomosine H (5) and J (7) were also confirmed by semisynthesis from phomosine A (1). The remaining four known compounds [phomosines A-D (1-4)] were identified by comparing their spectroscopic data with those reported in the literature. The four known metabolites were biologically active. Of the novel metabolites, only 6 was antifungal and antibacterial. PMID- 22312737 TI - Isolation and characterization of a new benzofuran from the fungus Alternaria sp. (HS-3) associated with a sea cucumber. AB - A new compound, 4-acetyl-5-hydroxy-3, 6, 7-trimethylbenzofuran-2(3H)-one (1), together with two known compounds, 2-carboxy-3-(2-hydroxypropanyl) phenol (2) and 5-methyl- 6-hydroxy-8-methyoxy-3-methylisochroman (3) were isolated from the fungus Alternaria sp. (HS-3) associated with a sea cucumber from the Yellow Sea in China. Their structures were elucidated by spectral methods. PMID- 22312738 TI - Potent toxic macrocyclic trichothecenes from the marine-derived fungus Myrothecium verrucaria Hmp-F73. AB - Activity-guided fractionation of a methanol extract from the culture broth of Myrothecium verrucaria Hmp-F73, a fungus associated with the sponge Hymeniacidon perleve, afforded six macrocyclic trichothecenes, verrucarin J (1), 8 hydroxyverrucarin J (2), verrucarin A (3), 8-acetoxyroridin H (4), isororidin E (5), and roridin E (6), along with trichoverrin B (7). All seven metabolites displayed potent toxicity to the brine shrimp (Artemia salina). In addition, compounds 2, 3, and 6 showed weak phytotoxic activities against lettuce seeds. A preliminary structure-activity relationship of the metabolites is also discussed. PMID- 22312739 TI - Synthesis and bioactivity of novel coumarin derivatives. AB - A series of coumarin derivatives (6-8) containing (E)-methyl 2-(methoxyimino)-2 phenylacetate, (E)-2-(methoxyimino)-N-methyl-2-phenylacetamide and methyl methoxy(phenyl)carbamate were synthesized from substituted resorcinols (1) and substituted beta-keto esters (2) as starting material via cyclization and condensation reactions. The test results indicated that (E)-methyl 2-{2-[(3-hexyl 4-methyl-coumarin-7-yloxy)methyl]phenyl}-2-(methoxyimino)acetate (6f) was the optimal structure with good fungicidal activity against cucumber grey mold (CGM) giving 100% control at 100 mg L(-1) concentration, much higher than that of coumoxystrobin. Methyl 2-[(3,4-dimethyl-coumarin -7 yloxy)methyl]phenyl(methoxy)carbamate (8a) was another optimal structure with good fungicidal activity against wheat powdery mildew (WPM) showing 100% control at 50 mg L(-1) concentration, at the same level as that of the commercial kresoxim-methyl, and very significantly higher than that of coumoxystrobin (no control against WPM at 400 mg L(-1)). PMID- 22312740 TI - Kinase inhibitory, haemolytic and cytotoxic activity of three deep-water sponges from North Western Australia and their fatty acid composition. AB - The c-AMP dependent protein kinase (PKA) inhibition, haemolytic activity, and cytoxicity of 21 extracts obtained from North Western Australian sponges collected from depths of 84-135 m were investigated. Hexane extracts from Ircinia/Sarcotragus sp. and Geodia sp. displayed PKA inhibitory activities of 100 and 97% respectively (at 100 microg/mL), while aq. methanol extracts from Haliclona sp. exhibited potent haemolytic activity (75%) and hexane extracts from Geodia sp. were highly toxic (88%) to the brine shrimp Artemia franciscana. As the non-polar extracts gave the greatest PKA inhibition, these were further analysed by GC-MS and 29 fatty acids were identified in the highest proportions in Ircinia/Sarcotragus sp. > Haliclona sp. > Geodia sp. In contrast to shallow water sponges that are dominated by polyunsaturated fatty acids with a high percentage of long chain fatty acids, LCFAs (C24-C30), the deep-sea sponges investigated herein were all found to be rich in saturated fatty acids, in particular C14-C20 fatty acids, including odd and branched chain fatty acids, with only low levels (0-10%) of LCFAs. Screening of the PKA inhibitory activity of a series of commercially available fatty acids identified C14-C18 fatty acids as possessing significant PKA inhibitory activity that may contribute to the activity observed in the sponges studied. PMID- 22312741 TI - Antimicrobial and cytotoxic effects of Mexican medicinal plants. AB - The antimicrobial effects of the Mexican medicinal plants Guazuma ulmifolia, Justicia spicigera, Opuntia joconostle, O. leucotricha, Parkinsonia aculeata, Phoradendron longifolium, P. serotinum, Psittacanthus calyculatus, Tecoma stans and Teucrium cubense were tested against several human multi-drug resistant pathogens, including three Gram (+) and five Gram (-) bacterial species and three fungal species using the disk-diffusion assay. The cytotoxicity of plant extracts on human cancer cell lines and human normal non-cancerous cells was also evaluated using the MTT assay. Phoradendron longifolium, Teucrium cubense, Opuntia joconostle, Tecoma stans and Guazuma ulmifolia showed potent antimicrobial effects against at least one multidrug-resistant microorganism (inhibition zone > 15 mm). Only Justicia spicigera and Phoradendron serotinum extracts exerted active cytotoxic effects on human breast cancer cells (IC50 < or = 30 microg/mL). The results showed that Guazuma ulmifolia produced potent antimicrobial effects against Candida albicans and Acinetobacter lwoffii, whereas Justicia spicigera and Phoradendron serotinum exerted the highest toxic effects on MCF-7 and HeLa, respectively, which are human cancer cell lines. These three plant species may be important sources of antimicrobial and cytotoxic agents. PMID- 22312742 TI - Chemometrics evaluation of the herbal drug Andrographis paniculata. AB - A fingerprint was developed to evaluate ten genotypes of Andrographis paniculata (a herbal drug) collected from different geographical locations. The genotypes were assessed by HPLC and the chromatogram areas were used to construct fingerprints. Between the two fingerprints, vector of differences was defined. The scalar mean of the deviated vector was used for statistical analysis. By incorporating appropriate chemometric methods better differentiation of samples was achieved. This provides tools for extracting relevant chemical information from the obtained data. The developed method can be used as a quality control tool for rapid authentication, identity, assessment and selection of good quality natural drug from a wide variety of herbal samples. PMID- 22312743 TI - Garcina cambogia leaf and seawater for tannase production by marine Aspergillus awamori BTMFW032 under slurry state fermentation. AB - Garcinia gummi-gutta (syn. G. cambogia, G. quaesita), known to have medicinal properties, was evaluated as a substrate and inducer for tannase production by a marine Aspergillus awamori BTMFW032, under slurry state fermentation using Czapekdox-minimal medium and sea water as the cultivation medium. Among the various natural tannin substrates evaluated, Garcinia leaf supported maximal tannase production. The cultivation conditions and components of the cultivation medium were optimized employing response surface methodology. The experimental results were fitted to a second-order polynomial model at a 92.2% level of significance (p < 0.0001). The maximal tannase activity was obtained in a slurry state medium containing 26.6%, w/v, Garcinia leaf, supplemented with 0.1% tannic acid as inducer. The optimum values of pH, temperature and inoculum concentration obtained were 5.0, 40 degrees C and 3%, respectively. A Box-Behnken model study of the fermentation conditions was carried out, and the best production of tannase was registered at 40 degrees C without agitation. Optimization strategy employing response surface methodology led to nearly 3-fold increase in the enzyme production from 26.2 U/mL obtained in unoptimized medium to 75.2 Units/mL in Box Behnken design, within 18 h of fermentation. It was observed that sea water could support maximal tannase production by A. awamori compared with other media suggesting that the sea water salts could have played an inducer role in expression of tannase encoding genes. To the best of our knowledge, this is the first report on production of tannase, an industrially important enzyme, utilizing Garcinia leaf as substrate under slurry state fermentation by marine A. awamori and sea water as the cultivation medium. PMID- 22312744 TI - Gas chromatographic quantitative analysis of methanol in wine: operative conditions, optimization and calibration model choice. AB - The influence of the wine distillation process on methanol content has been determined by quantitative analysis using gas chromatographic flame ionization (GC-FID) detection. A comparative study between direct injection of diluted wine and injection of distilled wine was performed. The distillation process does not affect methanol quantification in wines in proportions higher than 10%. While quantification performed on distilled samples gives more reliable results, a screening method for wine injection after a 1:5 water dilution could be employed. The proposed technique was found to be a compromise between the time consuming distillation process and direct wine injection. In the studied calibration range, the stability of the volatile compounds in the reference solution is concentration-dependent. The stability is higher in the less concentrated reference solution. To shorten the operation time, a stronger temperature ramp and carrier flow rate was employed. With these conditions, helium consumption and column thermal stress were increased. However, detection limits, calibration limits, and analytical method performances are not affected substantially by changing from normal to forced GC conditions. Statistical data evaluation were made using both ordinary (OLS) and bivariate least squares (BLS) calibration models. Further confirmation was obtained that limit of detection (LOD) values, calculated according to the 3sigma approach, are lower than the respective Hubaux Vos (H-V) calculation method. H-V LOD depends upon background noise, calibration parameters and the number of reference standard solutions employed in producing the calibration curve. These remarks are confirmed by both calibration models used. PMID- 22312745 TI - Composition and biological potential of essential oil from Thelechitonia trilobata growing in South Africa. AB - Thelechitonia trilobata is regarded as a troublesome weed that grows to form a dense blanket over the soil preventing the growth of other crops in farmland. Although the plant is regarded as a notorious, invasive plant, its chemical composition and biological potential have not been reported. The essential oil was isolated from the fresh leaves of T. trilobata using hydrodistillation. alpha Pinene (21.6%), alpha-phellendrene (21.0%), limonene (12.8%) and germacrene D (7.5%) were the major constituents of the oil. The essential oil was screened against agricultural pests. The anti-tick properties were tested on Ripicephalus e. ervertsi found on sheep, while repellency, fumigation, and contact toxicity tests were carried out with maize weevils. Except for the contact toxicity test, all other bioassays gave positive results. PMID- 22312746 TI - Chemical composition and antibacterial activity of essential oil from Salvia mukerjeei. AB - The composition of steam volatile oil from aerial parts of Salvia mukerjeei Bennet & Raizada (Lamiaceae) was analyzed by capillary GC and GC-MS. The oil was rich in sesquiterpene hydrocarbons (67.3%). Among 71 identified constituents representing 91.7% of the oil, beta-caryophyllene (28.7%), gamma-muurolene (15.5%) and dehydro-aromadendrane (9.5%), were the principal constituents. The oil was tested against ten bacterial strains and was active against Enterococcus faecalis, Erwinia chrysanthemi and Agrobacterium tumefaciens. PMID- 22312747 TI - Revealing indigenous Indonesian traditional medicine: anti-infective agents. AB - Indonesia is rich in medicinal plants which the population has used traditionally from generation to generation for curing diseases. Our interest in the treatment of infectious diseases has lead to the investigation of traditional Indonesian treatments. In this review, we present a comprehensive review of ethnopharmacologically directed screening in Indonesian medicinal plants to search for new anti-viral, antimalarial, anti-bacterial and anti-fungal agents. Some potent drug leads have been isolated from Indonesian medicinal plants. Further research is still required for the lead development as well as the search for new bioactive compounds from the enormous medicinal plant resources. PMID- 22312748 TI - Medicaid in South Dakota: update for physicians. PMID- 22312749 TI - Intensive blood pressure control in diabetes. AB - Contemporary standards of care, including many "quality improvement" and "pay-for performance" measures, indicate that aggressive blood pressure control should be instituted in patients with type 2 diabetes. Is this consistent with the evidence? This was recently the topic of a Sioux Falls Family Residency Program Journal Club presentation, in which we found the answer is a resounding "No". PMID- 22312750 TI - Regional Infant and Child Mortality Review Committee 2010 final report. AB - The 2010 annual report of the Regional Infant and Child Mortality Review Committee (RICMRC) is presented. Since 1997, RICMRC has sought to achieve its mission to "review infant and child deaths so that information can be transformed into action to protect young lives." For the year 2010, the Committee reviewed 15 deaths from Minnehaha, Turner, Lincoln, Moody, Lake, McCook, Union, Hanson, Miner and Brookings counties that met the following criteria: Children under age 18 dying subsequent to hospital discharge following delivery. Children who either died in these counties from causes sustained in them, or residents who died elsewhere from causes sustained in the 10-county region. The acronym SUID (Sudden Unexpected Infant Death) is being increasingly used by investigators of infant deaths. SUID is an intentionally broad category used for any sudden infant death when the cause of death is unapparent or multifactorial. Sudden Infant Death Syndrome (SIDS) is a subset of SUID, which in addition to SIDS includes sudden unexpected infant deaths of any cause. One death categorized as SIDS occurred in 2010. The committee has observed a stable decline in the number of deaths due to SIDS for the last several years with the exception of two SIDS deaths that occurred in 2008. The national SIDS rate of 0.57 per 1000 live births' would suggest that our region should have one SIDS death per year. It would appear that on average, our region's SIDS incidence is close to that number. Many investigators believe that a "diagnostic drift" is occurring in the SIDS determination. These investigators believe that some deaths certified as SIDS in earlier years may now be classified as "undetermined," or in the new terminology, SUID. Overall the number of SUID deaths has remained relatively stable over the last decade. In those years when there were spikes of infant deaths, the increases were largely due to an increase in the number of "undetermined" deaths. The majority of our "undetermined" manners of infant death appear to be related to concerns about possible asphyxial risks (e.g., overlaying, re-breathing and true suffocation) emphasizing the need to promote safe sleeping environments. Only one motor vehicle-related child death occurred in 2010, which represents a steady decline in deaths from a peak of nine deaths in 2005. PMID- 22312751 TI - Vancomycin in the treatment of serious methicillin-resistant Staphylococcus aureus infections: time to move on to alternative agents? PMID- 22312752 TI - Care transition. PMID- 22312753 TI - Exercise: prescription for health--promoting and prescribing physical activity. PMID- 22312754 TI - [Deaf blind persons - the right to full participation in life]. PMID- 22312755 TI - [Touch with respect. A loving way to interact with babies and children with massage]. PMID- 22312756 TI - [Experiencing intercultural nursing competence in general care - Ghana as instructional site]. PMID- 22312757 TI - [Stuttgart continuing education for FGKiK (family health and pediatric nurse). A wide range of topics, in depth knowledge]. PMID- 22312758 TI - [Difficult medical decisions: emotions and ethics in pediatrics]. PMID- 22312759 TI - [ESBL (extended spectrum beta-lactamase) pathogens in the newborn unit: harmless colonizing bacteria or mortal threat?]. PMID- 22312760 TI - [Deaf blindness - hearing and vision handicap]. PMID- 22312761 TI - [Krefeld Day of Pediatric Nursing. Family oriented health and pediatric nursing]. PMID- 22312762 TI - ["Proven effectiveness studies..." What does concrete actually mean?]. PMID- 22312763 TI - [The resistance trap (interview by Hardy-Thorsten Panknin)]. PMID- 22312764 TI - [Costs for MMR vaccination will be covered]. PMID- 22312765 TI - [Parliamentarians informed: children are entitled to the highest level of health]. PMID- 22312766 TI - [The NAW book (interview by Hardy-Thorsten Panknin)]. PMID- 22312767 TI - [A memorial celebration for parents and family of young deceased children]. PMID- 22312768 TI - [International survey: mothers of premature infants need more information and support]. PMID- 22312769 TI - [Happy parenting or family burden?]. PMID- 22312770 TI - [Sad accident record in summer: every week a severe defenestration accident in children]. PMID- 22312771 TI - [Can vitamins increase longevity?]. PMID- 22312772 TI - Joint Commission launches new core measure solution exchange: accelerating change by expanding access to data. PMID- 22312773 TI - Update: Urgent care and convenient care clinic standards applicability changes. PMID- 22312774 TI - Accepted: Revised laboratory proficiency testing requirement. PMID- 22312775 TI - Errata: Revision to note regarding level of disinfection: referenced at IC.02.02.01, EP 2. PMID- 22312776 TI - Home Health Standards Review Project focuses attention on high-value requirements. PMID- 22312777 TI - Joint Commission top standards compliance issues for 2010: challenging requirements identified. PMID- 22312778 TI - Clarification: Eligibility for home care accreditation based strictly on location of services. PMID- 22312779 TI - Joint Commission's pathology reporting requirements consistent with the Commission on Cancer. PMID- 22312780 TI - Tracer methodology evolves to include detailed exploration of several high-risk areas: second generation tracers now in use for some hospital, critical access hospital on-site surveys. PMID- 22312781 TI - Approved: Policy regarding health care staffing firms that cease to place employees. PMID- 22312782 TI - Accepted: Updated fire protection systems requirements for hospitals. PMID- 22312783 TI - Clarification: Assessing baseline coagulation status under NPSG.03.05.01. PMID- 22312784 TI - Approved: Revision to certification standard regarding A1C testing for inpatient diabetes care. PMID- 22312785 TI - The Joint Commission recognizes top performers on key quality measures: new program rewards hospitals for achievement and excellence. PMID- 22312786 TI - Errata: 2012 accreditation decision rules. PMID- 22312787 TI - Approved: No PPR submission required in year of the triennial or biennial survey. PMID- 22312788 TI - New Speak Up campaigns for patient education. PMID- 22312789 TI - Accreditation manual updates to mail to all accredited organizations: 2012 certification manuals also mailing. PMID- 22312790 TI - Joint Commission realigns telemedicine requirements with CMS changes. PMID- 22312791 TI - Personal care and support services standards review focuses on high-value requirements. PMID- 22312792 TI - Top standards compliance issues for first half of 2011. PMID- 22312793 TI - 401(k) plan asset allocation, account balances, and loan activity in 2010. AB - THE BULK OF 401(K) ASSETS CONTINUED TO BE INVESTED IN STOCKS: On average, at year end 2010, 62 percent of 401(k) participants' assets were invested in equity securities through equity funds, the equity portion of balanced funds, and company stock. Thirty-three percent were in fixed-income securities such as stable value investments and bond and money funds. SEVENTY PERCENT OF 401(K) PLANS INCLUDED TARGET-DATE FUNDS IN THEIR INVESTMENT LINEUP AT YEAR-END 2010: At year-end 2010, 11 percent of the assets in the EBRI/ICI 401(k) database were invested in target-date funds and 36 percent of 401(k) participants held target date funds. Also known as lifecycle funds, they are designed to offer a diversified portfolio that automatically rebalances to be more focused on income over time. MORE NEW OR RECENT HIRES INVESTED THEIR 401(K) ASSETS IN BALANCED FUNDS, INCLUDING TARGET-DATE FUNDS: For example, at year-end 2010, 44 percent of the account balances of recently hired participants in their 20s were invested in balanced funds, compared with 42 percent in 2009, and about 7 percent in 1998. A significant subset of that balanced fund category is target-date funds. At year end 2010, 35 percent of the account balances of recently hired participants in their 20s were invested in target-date funds, compared with 31 percent at year end 2009. 401(K) PARTICIPANTS CONTINUED TO SEEK DIVERSIFICATION OF THEIR INVESTMENTS: The share of 401(k) accounts invested in company stock continued to shrink, falling by more than a percentage point (to 8 percent) in 2010, continuing a steady decline that started in 1999. Recently hired 401(k) participants contributed to this trend: They tended to be less likely to hold employer stock. PARTICIPANTS' 401(K) LOAN BALANCES DECLINED SLIGHTLY IN 2010: In 2010, 21 percent of all 401(k) participants who were eligible for loans had loans outstanding against their 401(k) accounts, unchanged from year-end 2009, and up from 18 percent at year-end 2008. Loans outstanding amounted to 14 percent of the remaining account balance, on average, at year-end 2010, compared with 15 percent at year-end 2009. Loan amounts outstanding declined slightly from those in the past few years. THE YEAR-END 2010 AVERAGE ACCOUNT BALANCE IN THE DATABASE WAS 3.4 PERCENT HIGHER THAN THE YEAR BEFORE, BUT MAY NOT ACCURATELY REFLECT THE EXPERIENCE OF TYPICAL 401(K) PARTICIPANTS IN 2010: To understand changes in 401(k) participants' average account balances, it is important to analyze a sample of consistent participants. As with previous EBRI/ICI updates, analysis of a sample of consistent 401(k) participants (those that have been in the same plan since 2003) is expected to be published in 2012. PMID- 22312794 TI - Findings from the 2011 EBRI/MGA Consumer Engagement in Health Care Survey. AB - SEVENTH ANNUAL SURVEY: This Issue Brief presents findings from the 2011 EBRI/MGA Consumer Engagement in Health Care Survey. This study is based on an online survey of 4,703 privately insured adults ages 21-64 to provide nationally representative data regarding the growth of consumer-driven health plans (CDHPs) and high-deductible health plans (HDHPs), and the impact of these plans and consumer engagement more generally on the behavior and attitudes of adults with private health insurance coverage. Findings from this survey are compared with EBRI's findings from earlier surveys. ENROLLMENT CONTINUES TO GROW: The survey finds continued growth in consumer-driven health plans: In 2011, 7 percent of the population was enrolled in a CDHP, up from 5 percent in 2010. Enrollment in HDHPs increased from 14 percent in 2010 to 16 percent in 2011. The 7 percent of the population with a CDHP represents 8.4 million adults ages 21-64 with private insurance, while the 16 percent with a HDHP represents 19.3 million people. Among the 19.3 million individuals with an HDHP, 38 percent (or 7.3 million) reported that they were eligible for a health savings ccount (HSA) but did not have such an account. Overall, 15.8 million adults ages 21-64 with private insurance, representing 13.1 percent of that market, were either in a CDHP or were in an HDHP that was eligible for an HSA but had not opened the account. When their children are counted, about 21 million individuals with private insurance, representing about 12 percent of the market, were either in a CDHP or an HSA eligible plan. MORE COST-CONSCIOUS BEHAVIOR: Individuals in CDHPs were more likely than those with traditional coverage to exhibit a number of cost-conscious behaviors. They were more likely to say that they had checked whether their plan would cover care; asked for a generic drug instead of a brand name; talked to their doctor about treatment options and costs; talked to their doctor about prescription drug options and costs; developed a budget to manage health care expenses; checked a price of service before getting care; and used an online cost tracking tool. CDHP ENROLLEES MORE ENGAGED IN WELLNESS PROGRAMS: CDHP enrollees were more likely than traditional plan enrollees to report that they had the opportunity to fill out a health risk assessment, and they were also more likely to report that they had access to a health promotion program. CDHP enrollees were also more likely to report that they had been offered a cash incentive or reward to participate in a wellness program when a program was offered. HDHP enrollees were less likely to report having the opportunity to fill out a health risk assessment and to have access to a health promotion program. FINANCIAL INCENTIVES MATTER: When it comes to participating in a wellness program, CDHP enrollees were more likely than traditional plan enrollees to take advantage of the health risk assessment but not the health promotion program. Among those participating, the reasons they gave were that they were offered incentive prizes and reduced premiums. Among those not participating, the reasons they gave were that they could make changes on their own; they lacked time; and they were already healthy. Financial incentives were more a factor for CDHP enrollees than for traditional plan enrollees when it came to participating in wellness programs. CONSUMER USE OF TECHNOLOGY: A significant portion of the population reported using a smartphone, and 1 in 5 reported using a tablet. Among them, about one-quarter reported using an app for health-related purposes. Among those not using an app, nearly one-half were interested in using one. PMID- 22312795 TI - Green house gas emissions from open field burning of agricultural residues in India. AB - In India, about 435.98 MMT of agro-residues are produced every year, out of which 313.62 MMT are surplus. These residues are either partially utilized or un utilised due to various constraints. To pave the way for subsequent season for agriculture activity, the excess crop residues are burnt openly in the fields, unmindful of their ill effects on the environment. The present study has been undertaken to evaluate the severity of air pollution through emission of green house gases (GHGs) due to open field burning of agro-residues in India. Open field burning of surplus agro-residues in India results in the emission of GHG. Emissions of CH4 and N2O in 1997-98 and 2006-07 have been 3.73 and 4.06 MMT CO2 equivalent, which is an increase of 8.88% over a decade. About three-fourths of GHG emissions from agro-residues burning were CH4 and the remaining one-fourth were N2O. Burning of wheat and paddy straws alone contributes to about 42% of GHGs. These GHG emissions can be avoided once the agro-residues are employed for sustainable, cost-effective and environment- friendly options like power generation. PMID- 22312796 TI - Air Pollution Tolerance Index (APTI) of some tree species growing near rail roads of Madurai, Tamil Nadu (India). AB - Biological monitoring and assessment studies due to urban--rail road pollutants were carried out using Air Pollution Tolerance Index (APTI) of plants. Four plant (leaf) parameters--namely ascorbic acid, total chlorophyll, relative water content and leaf extract pH were combined together in a formulation signifying the APTI of plants. APTI was calculated for five different species such as Azadirachta indica, Delonix regia, Ficus religiosa, Pongamia pinnata and Polyalthia longifolia growing in two different areas, i.e. control area and along the railway track of Madurai, Tamil Nadu (India). The control site was selected in the college campus. None of the four plant parameters indicated a consistent response to pollutants. In the present study, Delonix regia and Pongamia pinnata lost the tolerance towards air pollutants and became more sensitive, but Azadirachta indica, Ficus religiosa, and Polyalthia longifolia indicated high APTI values over control area and hence considered as tolerant species. The APTI of plants showed a marked gradation as the pollutant load decreased from rail road to control area. The APTI can be used as a good indicator of impact of the air pollution on plants. PMID- 22312797 TI - Ambient air quality monitoring during the H1N1 influence period in Pune (India). AB - Ambient air quality in an urban area is directly linked with activity level in the city including transport, business and industrial activities. Maharashtra Pollution Control Board (MPCB) has established an ambient air quality network in the city including state-of-the-art continuous air quality monitoring stations which indicate short duration air quality variations for criteria and non criteria pollutants. The influence of H1N1 outbreak in Pune hitting its worst pandemic condition, led the civic authorities to implement stringent isolation measures including closure of schools, colleges, business malls, cinema halls, etc. Additionally, the fear of such a pandemic brought the city to a stand still. It was therefore necessary to assess the impacts of such activity level on ambient air quality in the city. It has been observed that such events have positive impacts on air quality of the city. There was a decrease in PM concentration almost to the tune of 30 to 40% if the impacts of precipitation, i.e. seasonal variations, are taken into account. Similarly, the non criteria pollutants too showed a marked but unusual decrease in their concentrations in this ever growing city. The influence of these in turn led to lowered concentrations of secondary pollutants, i.e. O3. Overall, the ambient air quality of Pune was found to be improved during the study period. PMID- 22312798 TI - Heavy metal accumulation in agricultural soils around a coal fired thermal power plant (Farakka) in India. AB - Agricultural soils around the ash dumping sites of one of the largest thermal power plant (TPP) in India located at Farakka, West Bengal were assessed for some heavy metal (Pb, Cd, Cr, As, Cu, Zn, Ni and Fe) distribution in association with other physicochemical components and compared with the control soils collected from far away of TPP. The toxic group metals (Pb, Cd, Cr and As) were well differentiated by their higher values of variability and non-normal distribution from the biologically essential metals (Cu, Zn, Ni and Fe). The statistical analysis of the heavy metals revealed that the two probable sources (Eigen values) in affected soils are responsible for their distribution; the more dominant one contributed the toxic metals and less dominating source contributed the essential heavy metals. While in control soils, no distinct separation of sources of the metals were found out signifying that the natural common sources could play active role in metal distributions. Although EF (Enrichment Factor) values of toxic metals are higher with large fraction of anthropogenic sources, yet (Igeo) (Geo-accumulation Index) values indicate moderate to unpolluted condition of the soils in respect to Pb, Cd and As. The calculated PLI (Pollution Load Index) values (1.88) considering all the metals also support the findings. Since there are no other sources of industrial effluents in the study area except the TPP, it can be said that the enrichment of these metals is solely attributed to their input from the ash contamination. For this, considerable degree of enrichment of toxic group of metals occurred in these soils. PMID- 22312799 TI - Assessment of environmental variables in Cauvery River and its tributaries. AB - This research paper pertains to the variation in water quality with special reference to physicochemical and biological parameters in Cauvery River and its tributaries in India over a period of 1 year. The quality of water in four streams of Cauvery River in Mysore, Mandya and Chamaraja Nagar districts, where many small scale sugar, paper industries and agricultural lands are located were analyzed. Sampling was carried out from Cauvery and its tributaries which were designated as stations 1, 2, 3 & 4 (all towards down streams of Cauvery River). The river water composition is increasingly dominated by PO4, NO3 Cl at stations 3 & 4 compared to stations 1 & 2. Significant spatial variations were observed in water level, transparency, turbidity, colour, DO, BOD, NO3, NO2 and total hardness among the physico-chemical parameters at the study locations. The DO level at stations 3 & 4 was lower than 5.0 mg/L, which is the recommended minimum allowable limit for aquatic life. 30 species of phytoplanktons were identified under five classes: viz, Chlorophyceae, Bacillariophyceae, Cyanophyceae, Euglenophyceae and Desmidaceae. About 20 algal species were recorded at station 1, 16 at station 2,13 species at station 3 and 14 species at station 4. The overall diversity and density of algae at four stations was significantly different. A posterior comparison revealed that stations 3 and 4 are the cause of significant difference. The chlorophyceae members, which dominated the algal community, were found to tolerate the effluent effect at stations land 2. Low algal diversity and negative impact on the biotic and abiotic environment were experienced at stations 3 and 4 throughout the duration of sampling, because of man made activities. PMID- 22312800 TI - Variation in calcium and magnesium ratio with increasing electrical conductivity of groundwater from shallow basaltic aquifers of Maharashtra (India). AB - The hydrochemical investigations of 523 groundwater samples from shallow basaltic aquifers of Maharashtra (India) have shown that the Ca/Mg ratio decreases gradually in the groundwater with increasing EC. The ratio was found high for the groundwater having EC less than 500 microS/cm representing a typical water from the basaltic aquifer having more Ca than Mg. The ratio decreases beyond EC of 500 microS/cm showing an increase in concentration of Mg as compared to Ca. The Mg concentration reaches maximum in the groundwater having EC greater than 2000 microS/cm. This decrease in Ca/Mg ratio with increase in mineralisation is possibly due to the percolation of domestic sewage and animal waste to groundwater. PMID- 22312801 TI - Impact of textile dyeing industries effluent on groundwater quality in Karur Amaravathi River basin, Tamil Nadu (India)--a field study. AB - Karur is an industrial town located on the bank of river Amaravathi. There are 487 textile processing units in operation and discharge about 14610 kilo litres per day of treated effluent into the river. The groundwater quality in the downstream is deteriorated due to continuous discharge of effluent. In order to assess the present quality of groundwater, 13 open wells were identified in the river basin around Karur and samples were collected during pre-monsoon, post monsoon and summer, and analyzed for physico-chemical parameters. TDS, total alkalinity, total hardness, calcium, chlorides and sulphates exceeded the desirable limit. Amaravathi River water samples were also colleted at the upstream and downstream of Karur and the result shows the river is polluted. During summer season, there is no flow in the river and the river acts as a drainage for the effluent. Hence, there is severe impact on the groundwater quality in the downstream. The best option to protect the groundwater quality in the river basin is that the textile processing units should adopt zero liquid discharge (ZLD) system and completely recycle the treated effluent. PMID- 22312802 TI - Zooplankton's role in the distributional status of autochthonous Vibrio cholerae: a case study using principal component analysis. AB - Miscellaneous statistical approaches were applied to illustrate the influence exerted by different zooplankton groups on the survival and distributional status of autochthonous Vibrio cholerae in two diverse marine environments, Veli and Kochi, former with low nutrient loading and later with high nutrient loading. The data set has been factorised using principal component analysis (PCA) for extracting linear relationships existing among a set of variables. Box plots were derived from the PCA data and were graphically represented. Vibrio cholerae (VC) showed strong positive correlation to zooplanktons especially with crustacean copepods under low nutrient conditions which confirmed a clear association between VC and zooplanktons for its surveillance and distribution under low nutrient concentration, while under high nutrient loading VC rely only on the available nutrients. PMID- 22312803 TI - Geo - hydrological investigations and impact of water harvesting structures on groundwater potential in Anantapur District, Andhra Pradesh, India. AB - In this paper, the data pertaining to the rainfall, its departure from normal, moving mean rainfall, depth of water levels in pre-monsoon and post-monsoon seasons, groundwater availability, groundwater utilization and impact of storage of water in large water bodies are analyzed graphically. The results indicate that the groundwater is over exploited in many places in Anantapur District (India). The groundwater levels found fluctuating, when compared the observations in pre-monsoon and post-monsoon seasons. Hence, it is concluded that the construction of water harvesting structures at suitable locations will have a definite impact on the groundwater potential in Anantapur District. PMID- 22312804 TI - Study on quality of effluent discharge by the Tiruppur textile dyeing units and its impact on river Noyyal, Tamil Nadu (India). AB - In Tiruppur, 729 textile dyeing units are under operation and these units generate 96.1 MLD of wastewater. The untreated effluent was discharged into the Noyyal River till 1997. After the issuance of directions by Tamil Nadu Pollution Control Board (TNPCB) in 1997, these units have installed 8 common effluent treatment plants (CETP) consisting of physical, chemical and biological treatment units. Some of the units have installed individual ETP (IETP). The treated effluent was finally discharged into the river. The dyeing units use sodium chloride in the dyeing process for efficient fixing of dye in the fabric efficiently. This contributes high total dissolved solids (TDS) and chlorides in the effluent. CETPs and IETPs failed to meet discharge standards of TDS and chlorides and thereby significantly affected the river water quality. TDS level in the river water was in the range of 900 - 6600 mg/L, and chloride was in the range of 230 - 2700 mg/L. Orathupalayam dam is located across Noyyal river at 32 km down stream of Tiruppur. The pollutants carried by the river were accumulated in the dam. TDS in the dam water was in the range of 4250 - 7900 mg/L and chloride was in the range of 1600 - 2700 mg/L. The dam sediments contain heavy metals of chromium, copper, zinc and lead. In 2006, the High Court has directed the dyeing units to install zero liquid discharge (ZLD) plant and to stop discharging of effluent into the river. Accordingly, the industries have installed and commissioned the ZLD plant consisting of RO plant and reject management system in 2010. The effluent after secondary treatment from the CETP is further treated in RO plant. The RO permeate is reused by the member units. The RO reject is concentrated in multiple effect evaporator (MEE)/ mechanical vacuum re-compressor (MVR). The concentrate is crystallized and centrifuged to recover salt. The salt recovered is reused. The liquid separated from the centrifuge is sent to solar evaporation pan. The salt collected in the solar pan is bagged and stored in secure land fill facility. Thus, the discharge into the river is now stopped. However, the damage caused to the groundwater and soil contamination in the river basin is yet to be restored. PMID- 22312805 TI - Physico-chemical characteristics of groundwater in and around Surat City (India). AB - Groundwater samples were collected from different locations of Surat city, Gujarat (India). These samples from 32 locations of Surat city were analysed for their physico-chemical characteristics involving pH, colour, odour, hardness, chloride, alkalinity, COD, sulfate, TDS, SS, iron, Cu, boron, chromium, temperature and Langelier Saturation Index. On comparing the results against drinking water quality standards laid by Indian Council of Medical Research (ICMR) and World Health Organization (WHO), it is found that most of the water samples are non-potable. Most of the samples indicated Total Alkalinity, Hardness, Chloride and TDS values much higher than the permissible level stipulated by ICMR and WHO. Even at some places Langelier Saturation Index values found higher too. The high values of these parameters may have health implications and therefore these need attention. PMID- 22312806 TI - Evaluation of carbons derived from Gingelly oil cake for the removal of lead(II) from aqueous solutions. AB - The adsorption of lead(II) onto activated carbons prepared from Gingelly Oil Cake (GOC) by using thermal, sulphuric and zinc chloride activations was investigated. The effects of experimental parameters such as pH, initial concentration, contact time and adsorbents dosage on the lead(II) removal were studied. The data were fitted with Langmuir, Freundlich and Temkin models to describe the equilibrium isotherms. The kinetic data fitted well with Lagergren pseudo first order and pseudo second order models. The maximum adsorption capacity for lead(II) on adsorbents calculated from Langmuir isotherm was found to be 105.26 mg/g and 114.94 mg/g for thermally activated and sulphuric acid activated carbons respectively. R2 values show that Langmuir model fits best to sulphuric acid activated carbon and Freundlich model fits best to thermally activated and zinc chloride activated carbons. The kinetic rates were best fitted to pseudo second order model. FT-IR analysis was used to obtain information on the nature of possible interaction between adsorbents and metal ions. SEM images confirmed the adsorption of lead(II) onto GOC adsorbents through morphological observations. Thermodynamic study showed the feasibility of process and spontaneous nature of the adsorption. The adsorbents were also tested for the removal of lead(II) from lead battery synthetic wastewater. The results indicate that carbons derived from GOC could be used to effectively adsorb lead(II) from aqueous solutions and wastewaters. PMID- 22312807 TI - Adsorption of cationic and anionic organic dyes from aqueous solution using silica. AB - The adsorption of cationic crystal violet (CV) and anionic indigo carmine (IC) has been studied on silica to identify the soil polluting nature of organic dyes. The adsorption parameters like contact time, concentration, temperature and adsorbent dosage were optimized for maximum adsorption. The adsorptions of CV and IC on silica followed Freundlich and Langmuir adsorption isotherm and pseudo second order kinetics. The deltaS degrees, deltaH degrees and deltaG degrees of adsorption on silica are calculated by using Vant Hoff's plot. The adsorption isotherms and thermodynamic studies proved that the CV was adsorbed more than IC on silica. The dyes recovery has been studied from dyes adsorbed silica in water. Very poor recovery of CV and high recovery of IC were observed. The adsorption mechanism, high adsorption and very poor recovery of CV on silica proved that the CV is polluting the soil more than IC. The poor adsorption and high recovery of IC on silica is a supportive evidence for very less soil polluting nature of the IC. PMID- 22312808 TI - Adsorption of direct dye onto activated carbon prepared from areca nut pod--an agricultural waste. AB - Activated carbons are made from various agricultural wastes by physical and chemical activation. The preparation of activated carbon from agricultural waste could increase economic return and also provides an excellent method for the solid waste disposal thereby reduce pollution. Areca nut pod, which is an agricultural waste, has been used as a raw material to produce activated carbon (AAC) by four different methods. The adsorption of Direct blue dye used in textile industry on the porous areca nut pod activated carbon was investigated. The activated carbon AAC has an average surface area of 502 m2/g. CAC, the commercial reference was mainly micro porous with a surface area of 1026 m2/g .The study investigated the removal of direct dye from simulated water. The effects of adsorbent dosage, initial dye concentration, pH and contact time were studied. The results showed that as the amount of the adsorbent was increased, the percentage of dye removal increased accordingly. The results indicate that AAC could be employed as low-cost alternative to commercial activated carbon in wastewater treatment for the removal of acid dyes. PMID- 22312810 TI - [Adherence]. PMID- 22312809 TI - A study of fine aggregate replacement with fly ash an environmental friendly and economical solution. AB - The use of fly ash as a replacement of sand has a great potential to benefit our society in terms of reducing demand of natural sand, reducing environmental problems, conserving energy and reducing landfill area requirement. This paper presents an approach to increase the utilization of fly ash and conserve scarcely available natural sand for sustainable development. The experimental investigation by the inclusion of fly ash as a partial replacement of sand as compared to control cement mortar mixes indicated 50% to 100% increase in the compressive strength of mortar at 91 days. Replacement of 50% sand with fly ash can save about 0.4 m3 sand. Comparison of cost per N/mm2 compressive strength has shown about 40% to 60% saving in cost. Based on the experimental results, correlations are developed for finding out the compressive strength and cost at 28 and 91 days. Sand was replaced with 10% to 50% of fly ash by weight and 0.5, 0.55, 0.6 and 0.65 W/C ratios were used. Flow test performed for mortar revealed that as the percentage replacement of sand with the fly ash increased the flow of the mortar decreased. It was also observed that wet and dry densities were more than the control mortar for 10% & 20% replacement of sand with fly ash but for higher replacement percentage density reduced marginally. PMID- 22312811 TI - [Prognosis for branch retinal vein occlusion]. AB - PURPOSE: To evaluate the visual outcomes of various kinds of treatment for branch retinal vein occlusion (BRVO). METHODS: The medical records of 222 BRVO eyes without any previous treatment were reviewed. One-year visual acuity (VA) and 1 year visual gains (VG) were analyzed for each treatment. RESULTS: The one-year VA correlated with the initial VA and 1-year VG negatively correlated with the initial VA. The initial and 1-year VA of the observation group (17.6%) were 0.6 and 0.8, respectively. No difference in the 1-year VA was found among the various treatments and the average 1-year VG was 1.1 lines. The one-year VA of the single treatment group (36.0%) was 0.62 on average, without any difference between the various treatments, while only the PPV group had better 1-year VG (4.4 lines). The multiple treatment group (46.4%)showed worse initial VA (0.33), 1-year VA (0.39) and 1-year VG (0.7 line). CONCLUSIONS: Patients with better initial VA can be observed without any treatment. As a whole, the 1-year VG is about one line and some significant visual improvement can be expected regardless of the treatments. The PPV group showed larger visual gain for eyes with worse initial visual acuity. Approximately half of the patients could not achieve any improvement by a single treatment and had a poor visual prognosis. PMID- 22312812 TI - [Allergy related factors in tears of patients with vernal keratoconjunctivitis undergoing topical 0.1% tacrolimus treatment]. AB - PURPOSE: To investigate, using tear fluid analysis, the effects of topical 0.1% tacrolims therapy on the pathophysiology of vernal keratoconjunctivitis (VKC). SUBJECTS AND METHODS: Subjects were 6 eyes of 6 patients with VKC who underwent topical 0.1% tacrolims treatment twice a day and 5 eyes of 5 healthy volunteers as a control. Using the filter paper method, the tear fluid of the patients was sampled both before and 4 +/- 2 weeks after the treatment and once from the control subjects. Eosinophil cationic protein (ECP) in the tears was examined by the chemiimmunoluminescent enzyme immunoassay method and the chemokine profile of the tears was analyzed using an antibody-array. RESULTS: In terms of the chemokine profile, growth related oncogene (GRO) -alpha, eotaxin-2 and thymus and activation-regulated chemokine (TARC) in the VKC were elevated compared with those in the controls, but they decreased significantly after the treatment (p<0.05). ECP concentrations in the tears were 3092 +/- 1658 ng/ml (average +/- S. D.) for the pretreatment base-line and 464 +/- 775 for the posttreatment. ECP values for the pre-treatment time were statistically significantly higher than those for the post-treatment in 5 patients (p<0.05). CONCLUSION: Topical tacrolims treatment of VKC can suppress allergic inflammation associated chemokines such as eotaxin-2 and TARC. PMID- 22312813 TI - [Causes of patients' non-adherence with glaucoma medication dosing: systemic classification based on dosing schedule]. AB - PURPOSE: To study the causes of patients' nonadherence with the instruction of glaucoma medication dosing and to analyze them based on the dosing schedules by means of systemic classification. METHODS: Four hundred twenty eight patients who had been prescribed glaucoma medication for at least six months were studied. Adherence was ascertained by means of a predetermined questionnaire. Nonadherent patients were interviewed with stratified questionnaires to elicit the causes for the non-adherence, which were analyzed with cluster analysis. RESULTS: The total number of non-adherents (more than 3 doses missed per month) was 114 (26.6%). The non-adherence rate in the morning was 18.2% (51/280) and in the evening 24.7% (75/304); there was no significant difference. Structured interviews for the 114 non-adherents elicited 194 unique situational problems (1.7 +/- 0.6/individual), which were grouped into four major categories: 25 medication regimen factors (12.9%), 119 patients' related factors (61.3%), 6 provider-related factors (3.1%) and 44 environmental factors (22.7%). Patients' related factors showed the higher incidence compared with other factors in both dosing time (p<0.01): Sleeping and taking a bath caused 39 patients (20.1%) to miss medication in patients with eye drops' application in the evening. CONCLUSIONS: Each dosing time may have its own situational problems, which may be likely to be multidimensional and must considered with each individual patient. PMID- 22312814 TI - [Time course of changes in functional visual acuity and ocular wavefront aberration after instillation of ofloxacin gel-forming ophthalmic solution]. AB - PURPOSE: To investigate the influence of ofloxacin gel-forming ophthalmic solution on functional visual acuity (FVA) and ocular wavefront aberration. SUBJECTS AND METHODS: In the right eyes of 22 normal volunteers, FVA and ocular wavefront aberration were measured before and 1, 5, 10, 15, 30 minutes after the instillation of ofloxacin gel-forming ophthalmic solution (Gel group). Similar measurements were repeated after instillation of ofloxacin ophthalmic solution (Solution group) and ofloxacin ophthalmic ointment (Ointment group). The obtained data were compared among the three groups. RESULT: Although no significant changes in FVA and total ocular higher-order aberrations (HOAs) were observed in the Solution group, FVA and HOAs significantly deteriorated in the Gel group and Ointment group at 1 minute after instillation. These changes gradually returned to the baseline levels. These changes were remarkable in the Ointment group. FVA deteriorated significantly in the Ointment group as compared with the Gel group up to 5 minutes after instillation (p<0.0167). CONCLUSION: Instillation of ofloxacin gel-forming ophthalmic solution significantly decreases FVA and increases HOAs, but these changes are less and shorter than the ofloxacin ophthalmic ointment. PMID- 22312815 TI - [Case of retinal ischemia and retinal arteritis secondary to intravitreal nuclear drop]. AB - BACKGROUND: A rare case of retinal arteritis and retinal ischemia as an incomplete branch retinal artery occlusion is reported following dropped lens fragments into the vitreous body. CASE: A 69 year-old-woman had a cataract OD with corrected visual acuity of 0.4. When she underwent phacoemulsification on March 11, the posterior capsule was damaged and nucleus fragments dropped into a vitreous body. A few days later, the vitreous opacity increased. The corrected visual acuity OD dropped to 0.06 due to anterior chamber inflammation and the intraocular pressure increased to 26 mmHg. During a pars plana vitrectomy on May 7, some retinal whitening were observed and incomplete branch retinal artery occlusion was confirmed by fluorescence fundus angiography. The corrected visual acuity finally improved to 0.3, but the right visual field defect remained. CONCLUSION: Incomplete branch retinal artery occlusion caused by phacoanaphylactic endophthalmitis secondary to lens fragments in the vitreous cavity seems to be a rare condition related to retinal whitening. The timing of pars plana vitrectomy should be considered before retinal arterial sheathing or retinal whitening can be noted. PMID- 22312816 TI - Looking forward. PMID- 22312817 TI - PQRS reporting of the perioperative care measures group. PMID- 22312818 TI - The strategic planning experience of the Michigan Chapter. PMID- 22312819 TI - Rep. Larry Bucshon, MD, brings surgical perspective to public policy. PMID- 22312820 TI - Advanced en-route critical care during combat operations. PMID- 22312821 TI - Piti, piti, wazo fe nich li: little by little, the bird makes its nest. PMID- 22312822 TI - The ACS HPRI: shaping surgical workforce policy through evidence-based analyses. PMID- 22312824 TI - TST offers safety solutions. PMID- 22312823 TI - Protecting student athletes from traumatic brain injuries. PMID- 22312825 TI - [Young person's first-episode psychosis]. AB - Young person's first-episode psychosis may signify the onset of schizophrenia, psychotic depression or bipolar disorder. It can also be a brief condition resulting in full recovery. The psychosis may be caused by drugs. First-episode psychosis is usually preceded by a long period of nonspecific symptoms. Provision of close and active follow-up is important in the prodromal phase. Treatment of first-episode psychosis is individual. Usually it involves medication, individual discussions, psychotherapy or music therapy as well as family meetings. The therapy helps the young person become independent. PMID- 22312826 TI - [HIV--from a lethal disease to a chronic illness]. AB - Combination anti-HIV therapies revolutionized patient life expectancy in the mid 1990's. Afterwards, in the early 2000's, research focused on the adverse effects caused by HIV drugs. Among these, the most serious ones are myocardial infarction at young age, disturbances of kidney function, liver disorders, pancreatitis and osteoporosis. The worsening of prognosis, for instance in respect of cardiac diseases, observed approximately five years ago in patients due to pauses in HIV medication, has changed perspective. Currently it is being discussed whether the overall prognosis will be improved with HIV medication started as early as possible. PMID- 22312827 TI - [Systemic lupus erythematosus]. AB - Systemic lupus erythematosus (SLE) is a chronic syndrome with unknown etiology and polymorphic clinical picture occurring mainly in women. The patients have immunological abnormalities such as autoantibodies against nuclear structures. The prognosis has improved due to active early diagnostics and more efficient treatment of the disease. Mild forms of the disease are associated with fatigue, articular and muscular symptoms, skin rashes, pleuritis or pericarditis and minor changes in the blood. Severe SLE involves glomerulonephritis, complications in the central nervous system, cardiac and pulmonary complications and major changes in the blood. PMID- 22312828 TI - [Epigenetic modifications in cancer]. AB - Abnormal function of genes and modified gene expression patterns play a major role in cancer. Scientists have been investigating origins of human cancer for decades and debating the relative roles of genetic and epigenetic abnormalities in the process. Growing evidence indicates that epigenetics abnormalities together with genetic defects take part in aberrant gene regulation in all stages of cancer development, and no cancer has been identified that has purely genetic or epigenetic background. Epigenetic modifications bring new insights into cancer diagnostics, prognostics and therapy. PMID- 22312829 TI - [Objective measurement of physical activity in adults]. AB - Physical inactivity and overweight are important risk factors for several diseases. Brisk walking or jogging recommended currently for physical exercise may be too demanding for subjects having overweight or poor physical condition. The recommendations do not take daily physical activity into account either. Recording of the total amount and intensity of ambulatory physical activity by the accelerometers allows objective assessment of dose-response relations between physical activity and health. By using threshold values of the intensity of physical activity or step counts, more accurate and effective recommendations for physical exercise can be suggested. PMID- 22312830 TI - [Punch biopsy in the diagnosis of skin tumors]. AB - Punch biopsy is a feasible method in the early diagnosis of nonmelanotic skin cancer in primary health care, but should not be applied to lesions that appear clinically as melanomas. Small skin lesions suspected to be malignant can often be completely excised in primary health care. If the skin tumor is large, a biopsy from the tumor area is worth taking so that the edge of the tumor remains intact. A sufficient specimen for histological examination is usually obtained with a punch having a diameter of 3 to 4 millimeters. PMID- 22312831 TI - [Netherton syndrome--a rare form of inherited ichtyosis]. AB - Netherton syndrome is a rare skin disease classified into ichtyoses. It has a recessive pattern of inheritance. It is associated with scaly erythrodermia, bamboo hair defect, immunological abnormalities of varying severity, IgE-mediated allergic reactions, infections and defective temperature regulation that often leads to retarded growth and development of a newborn. The phenotype of the disease varies from mild skin symptoms to lethal forms of the disease. We describe two Finnish families, whose children were diagnosed with this disease. PMID- 22312832 TI - [Pott's puffy tumor--a rare complication of frontal sinusitis]. AB - Pott's puffy tumor is an extremely rare complication of frontal sinusitis. It is most typically found in young men. Streptococci, staphylococci or anaerobic bacteria are usually the causative agents. In our patients the inflammation was caused by Streptococcus milleri and Streptococcus pneumoniae. The treatment should be started with broad-spectrum antibiotics. The antibiotics are administered intravenously for 1 to 2 weeks and thereafter orally for at least four weeks. Paranasal sinuses must be operated, and if necessary, intracranial abscesses are treated neurosurgically. PMID- 22312833 TI - [Update on current care guidelines: Allergen specific immunotherapy]. AB - Immunotherapy involves the specific treatment of IgE-mediated allergic diseases, indicated for allergic rhinitis and conjunctivitis, allergic asthma, insect sting (bee and wasp) allergy, and food allergy (especially cow's milk, egg and wheat). Subcutaneous injection immunotherapy with pollens (both trees and grass), animal danders, insect venoms and house dust mite preparations for allergic rhinitis and asthma is effective for both adults and children. Sublingual immunotherapy indicated for allergic rhinitis caused by grass pollens (especially timothy), is effective and appears to be a safe route of administration. Specific oral tolerance induction is used in children over five years of age with severe food allergy. PMID- 22312834 TI - [Standard and above standard care in gynecology and obstetrics]. PMID- 22312835 TI - [Laparoscopic approach in the pelvic floor surgery]. AB - Laparoscopy offers great exposure and surgical detail, reduces blood loss and the need for excessive abdominal packing and bowel manipulation making it an excellent modality to perform pelvic floor surgery. Laparoscopic repair of level I or apical vaginal prolapse may be challenging, due to the need for extensive dissection and advanced suturing skills. However it offers the efficacy of open abdominal sacrocolpopexy, such as lower recurrence rates and less dyspareunia than sacrospinous fixation, as well as the reduced morbidity of a laparoscopic approach. PMID- 22312836 TI - [Diagnosis and management in women with lower urinary tract symptoms (LUTS) after burch colposuspension]. AB - OBJECTIVE: To demonstrate the significance of introital ultrasound of the lower urinary tract in the diagnostic algorithm in patients with lower urinary tract symptoms (LUTS) after Burch colposuspension. METHODS: Twenty six women with voiding dysfunction directly associated with prior anti-incontinence surgery (Burch colposuspension) were included in the study (Group A). The control group (Group B) consisted of twenty eight women after Burch colposuspension with a good clinical result without LUTS. Introital ultrasound was performed at rest and at maximum voluntary contraction to measure the monitored parameters (angle alpha: the inclination angle of the urethra, angle beta: the posterior urethrovesical angle, angle gamma: the angle between the axis of the symphysis and the line segment connecting the region of the internal urethral orifice and the lower margin of the symphysis, distance H: the distance between the internal urethral orifice and the horizontal axis running through the bottom edge of the symphysis, distance p: the distance between the internal urethral orifice and the lower margin of the symphysis). RESULTS: Significant differences were found in bladder neck position and mobility between those women with LUTS and control group. At a 5% confidence interval, both groups differ in mean values of the angles alpha, beta a gamma, and in the mean values of segments p and H on straining. Ventral displacement of the bladder neck (characterized by angles alpha and gamma) at rest and during straining was present in all women in group A. The difference was statistically significant (p=0,001). Angle beta also demonstrates abnormal position and minimal mobility of the bladder neck in group A. As a result of bladder neck disclocation in the ventral direction, at rest, this parameter shows significantly lower values in comparison with group B. This difference is more apparent on Valsalva, where as a result of minimal mobility of the bladder neck. This parameter has even lower values in group A in comparison with group B. The bladder neck in patients with LUTS after Burch colposuspension shows not only ventral displacement of the bladder neck but also a significant reduction in dorsocaudal movement during straining. CONCLUSION: In women with LUTS after Burch colposuspension, atypical changes in the position and mobility of urethra can be demonstrated when compared with women who underwent successful surgery for incontinence. PMID- 22312837 TI - [Prenatal diagnosis and management of fetuses with congenital diaphragmatic hernia]. AB - OBJECTIVE: The aim of this article is to review current options of prenatal diagnosis and management of fetuses with congenital diaphragmatic hernia at the Institute for the Care of Mother and Child. SETTING: Institute for the Care of Mother and Child, 3. LF UK, Prague. METHODS: Review of the literature. RESULTS: Prenatal diagnosis of congenital diaphragmatic hernia based on 2D ultrasound. Measurement of the lung-to-head ratio (LHR), observed to expected lung to head ratio (O/E LHR), side of the diaphragmatic defect, assessment of the liver position and presence of associated anomalies (negative prognostic factors) are used for prediction of outcome. Prenatal diagnosis can be suplemented by 3D ultrasonography and magnetic resonace imaging. An important part of succesful management of CDH is the referal of cases to a specialised center. PMID- 22312838 TI - [Quiscent trophoblastic disease]. AB - TYPE OF STUDY: Case report. SETTING: Center for trophoblastic disease in Czech Republic, Institute for care of mother and child, 3rd Faculty of Medicine of Charles University Prague. METHODS: The autors present a case of quiscent trophoblastic disease diagnosed at 27 years old primipara, secundigravida after previous molar pregnancy. The patient had low levels of serum hCG present for more than 18 months after the termination of pregnancy. After this period there was a malignant transformation associated with rapid elevation of hCG levels with need for chemotherapy which was succesfully completed. CONCLUSION: Quiscent (dormant, noninvasive) trophoblastic disease is a recently described unit defined by low levels of hCG present in patients serum and urine samples without any evidence of trophoblastic tumour or other source of hCG production. Quiscent trophoblastic disease is associated with high risk of malignant transformation. PMID- 22312839 TI - [Ultrasound imaging of normal fetal central nervous system at 8 to 12 weeks of gestation]. AB - With ongoing evolution of advanced ultrasound diagnostic in prenatal care the trend is to detect potential fetal anomalies in the first trimester if possible. Complex knowledge of normal fetal anatomy, embryology and ultrasound anatomy is important to be able to identify subtle abnormalities. In this review we demonstrate the possibilities of ultrasound imaging of fetal brain at late first trimester and describe normal central nervous system development week by week. Original images are presented. PMID- 22312840 TI - [Possibilities of 4D ultrasonography in imaging of the pelvic floor structures]. AB - Technological boom of the last decades brought urogynaecologists and other specialists new possibilities in imaging of the pelvic floor structures which may substantially add to search for etiology of pelvic floor dysfunction. Magnetic resonance imaging (MRI) is an expensive, less accessible method and may pose certain dyscomphort to the patient. 3D/4D ultrasonography overcomes these disadvantages and brings new possibilities especially in dynamic, real time imaging and consequently enables focus on functional anatomy of complex of muscles and fascial structures of the pelvic floor. With 3D/4D ultrasound we can visualise urethra and surrounding structures, levator ani and urogenital hiatus, its changes during muscle contraction and Valsalva manevre. This method has great potential in diagnostics of pelvic organ prolapse, it may bring new knowledge of factors contributing to loss of integrity of pelvic floor structures resulting in prolapse and incontinence. Studies exist which describe changes in urogenital hiatus after vaginal delivery, further studies of large numbers of patients during longer period of time are though necessary so that conclusions can be drawn for clinical praxis. PMID- 22312841 TI - [Use of ultrasound in labor]. AB - In the managing of labor, the obstetrician gets often to the border situations especially at the end of the second stage of labor, where only accurate diagnosis allows the make correct decisions on how to end the delivery. Since clinical vaginal examination does not always give complete informations about station and rotation of the head, the intrapartum fetal ultrasound showing the fetus inside the birth canal can refine and document the diagnosis and help us to decide. PMID- 22312842 TI - [Characteristics and prognosis of malignant disease of the breast in women of very low age]. AB - OBJECTIVE: This study aims to describe characteristics of malignant diseases of the breast in women of very low age (thus with breast cancer diagnosed before 35th year of age) and compare those characteristics with the phenotype of "average" breast cancer in Czech female population. METHODS: 98 women diagnosed with breast cancer before the age of 35 and treated between 2001 and 2010 in private medical center Medicon Praha s.r.o, were enrolled to this retrospective study. The control group of 100 women was constituted by random choice from patients older than 35 years at the time of diagnosis treated in the same time period. RESULTS: Size of the tumors at presentation were similar in both study groups. Tumors in younger group exhibited higher proliferative activity, higher grade and lower count of estrogen receptors. On the contrary, in the group of older women was significantly higher percentage of lobular type of cancer and also the proportion of in situ carcinomas. The number of multifocal tumors, positivity of HER-2/neu and progesterone receptors were all without statistically significant difference. In younger women neoadjuvant chemotherapy has been used more frequently. Prognosis of the disease did not differ in both groups. CONCLUSION: Tumors diagnosed in women younger than 35 years can be considered more aggressive. However, using adequate treatment makes the prognosis comparable in both age groups. PMID- 22312843 TI - [Robot assisted laparoscopic staging of endometrial cancer--comparison with standard laparotomy]. AB - OBJECTIVE: To describe our initial experience with robotically assisted laparoscopic staging of endometrial cancer patients as compared with previous cases staged by standard laparotomy. DESIGN: Original article. SETTING: Department of Obstetrics and Gynecology, Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc. METHODS: The first twenty patients with early stage endometrial cancer underwent hysterectomy, bilateral salpingo-oophorectomy, and pelvic/paraaortic lymphadenectomy using four-armed da Vinci S HD surgical system (TRH) and were compared with previous 20 cases of staging procedures as done by laparotomy (TAH). Age, body mass index (BMI), clinical stage of disease, grade, histopathology, nodal yield, operative time, estimated blood loss, hospital stay, recovery room stay and analgesic needs were documented and compared. RESULTS: Mean age of patients in the robotic surgery group was 64,55 (47-85) years and in the laparotomy group 62,95 years (35-79). BMI was 27,45 (19-34) in TRH and 32,2 (26-55) in TAH group. There was no difference in FIGO stage, grade and histopathology between both groups. Node yield was slightly higher in TRH (16,95) than in TAH (14,9) group. Operative time was 262,25 min. (170-390) for TRH and 141,6 min. (97-175) for TAH. Estimates of blood loss were 102 (10-300) ml in the robotic surgery group and 352,5 (200-500) ml for TAH group. The average hospital stay was longer for the laparotomy than the robot group (8,75 vs. 7,20 days respectively). There was one conversion to laparotomy in TRH group. Within the "learning curve" gradually shortening operation time, recovery time and lowering blood loss were observed with number of performed robotic operations. CONCLUSION: Robotic hysterectomy and staging is associated with lower blood loss, lower use of narcotics and shorter hospital stay than standard laparotomy during "learning curve" period. PMID- 22312844 TI - [Genital warts and HPV vaccination]. AB - OBJECTIVE: To present and overview of incidence of, and cost of care for, genital warts. SUBJECT: Review. SETTING: Department of Obstetrics and Gynecology, Palacky University and Faculty University, Olomouc; Office gynecology and primary care centre, Brno; Department of Obstetrics and Gynecology, Charles university in Prague-First Faculty of Medicine and General Faculty Hospital, Prague. METHOD: Literature review of incidence of, and cost of care for, genital warts in some european countries, North America and Australia. CONCLUSION: Genital warts exert a considerable impact on health services, a large proportion of which could be prevented through immunisation using the quadrivalent human papillomavirus vaccine. PMID- 22312845 TI - [Compare of misoprostol and dinoprost effectivity by induced second-trimester abortion]. AB - OBJECTIVES: To compare the effectivity and safety of second-trimester abortion induced by two different types of prostaglandins. TYPE OF STUDY: Retrospective study. SETTING: Department of Obstetrics and Gynecology, University Hospital Ostrava and Department of Obstetrics and Gynecology, University Hospital Olomouc. METHODS: Retrospective analysis of 128 second trimester abortions induced by misoprostol and 82 second trimester abortions induced by dinoprost. Total length of abortion, failure of the method, need for instrumental revision of the uterine cavity, request for epidural analgesia and length of hospital stay were compared. RESULTS: In total 210 women were included. Misoprostol was used in 128 cases and dinoprost in 82 cases. The average gestational age was 18+1 in misoprostol group and 20+2 in dinoprost group. Ninety two percent of women with misoprostol aborted within 24 hours while in the dinoprost group it was 68%, withing 16 hours the number of completed abortions was 62% (misoprostol) versus 48% (dinoprost). The method failed in 2% of cases with misoprostol and 7% of cases with dinoprost. CONCLUSION: We conclude that induction of second-trimester abortion with the use of misoprostol is safe, quick, non-invasive and comfortable method with low frequency of complications and side effects. PMID- 22312846 TI - [Transurethral injection of polyacrylamide hydrogel (Bulkamid) for the treatment of female stress urinary inkontinence and changes in the cure rate over time]. AB - OBJECTIVE: The objective of this study was to evaluate short term and long term efficacy of a transurethral injection (TUI) using bulking agent Bulkamid for female stress and mixed urinary incontinence. The hypothesis was that the cure rate of Bulkamid may slowly decreases over time. DESIGN: Retrospective clinical study. SETTINGS: Gynecological and Obstetric Clinic, 1 LF UK and VFN, Prague. MATERIALS AND METHODS: A retrospective study was performed on 25 women with urinary incontinence (stress 18; mixed 7), and 24 patients completed the study. Nineteen patients had previously undergone anti-incontinence surgery. The efficacy of TUI was evaluated 3 months (+/- 1 week) and an average of 13.5 months (range 6-30 months) after surgery. Subjective assessment of the leakage of urine was based on the International Consultation on Incontinence Questionnaire - Short form (ICIQ-UI SF) filled in before and three and - on average - 13.5 months after the surgery (minimum time after surgery was 6 months). Improvement in urinary incontinence was defined as a drop in the score of more than 50%. Objective assessment of leakage of urine was assessed by cough test. Ethical committee approval was obtained, and all subjects gave written informed consent to participate in the study. RESULTS: Mean age of patients was 69.7 (SD 16.22) years, mean body mass index (BMI) 27.56 (SD 3.42), and mean parity was 1.73 (SD 0.7). Objective assessment by cough test showed that 9/25 (36%) of patients had negative results for this test 3 months and 4/24 (16.7%) 13.5 months after the operation. Subjective assessment by the ICIQ-UI SF questionnaire showed that 7/25 (28%) of our patients were completely dry 3 months after the operation and 3/24 (12,5%) 13 months after the operation. 20/25 (80%) of patients were dry or improved 3 months after the operation and 14/24 (58.3%) 13.5 months after the operation. The mean score before the operation was 17.56 (SD 3.44), median 18; 3 months after the operation it was 5.68 (SD 5.51), median 5; and 13.5 months after the operation it was 8.25 (SD 5.49), median 7.5. The evaluation of the answers to the question "Overall, how much does leaking urine interfere with your everyday life?" showed a worsening of the situation to a statistical significant degree: 3 months after the operation the mean score was 2.38 (SD 2.28), while 13.5 months after the operation it was 3.79 (SD 2.96). CONCLUSIONS: The hypothesis that the cure rate of Bulkamid may slowly decreases as time passes after the operation was confirmed. PMID- 22312847 TI - [Quality and effectiveness of electronic fetal monitoring]. AB - OBJECTIVE: To evaluate effectiveness of electronic fetal monitoring methods during labor. DESIGN: A case series study. SETTING: Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic. METHODS: We followed 112 fetuses with simultaneous continuous monitoring (cardiotocography (CTG), intrapartal fetal pulse oxymetry (IFPO), and analysis of ST segment in fetal electrocardiogram (STAN)) during labor. We determined the effective time for every diagnostic tool. STATISTICS: histograms, Kolmogorov-Smirnov test, Spearman's coefficient; significance (alfa): p<0.05. RESULTS: The effective time decreased significantly in a row: CTG > STAN > IFPO (94.8% +/- 15.1% vs. 90.4% +/- 18.3% vs. 87.4% +/- 21.2%). STAN was the most effective tool in the second stage of labor (91.3% +/- 9.4%). CONCLUSION: The most effective fetal monitoring tool is CTG. However STAN is the best diagnostic method in the second stage of labor, because of its bio-signal quality. PMID- 22312848 TI - [The Czech Pharmaceutical Society remembers the 140th anniversary of its founding]. PMID- 22312849 TI - [On the question of special over-the-counter drugs]. AB - In the Czech Republic, special non-prescription over-the-counter (OTC) drugs are defined as the preparations which, according to their registration, can be sold over the counter without a prescription outside pharmacies. The paper outlines the development of the question of human and veterinary OTC drugs (lists of special OTC drugs, good practice of sellers of special OTC drugs) and compares the number and structure (indication group, selected medicinal products, dosage form) of human and veterinary drugs included into this group. PMID- 22312850 TI - [Clinical significance of cytochrome P450 genetic polymorphism--part IV. Cytochrome P450 3A4 and 3A5]. AB - The enzymes of cytochrome P450 3A subfamily are responsible for the metabolism of about 50% of commonly used drugs. High inter-individual variability in the activities of these enzymes has been described. The last fourth part of this review focuses on the influence of genetic polymorphism of CYP3A4 and CYP3A5 enzymes on drug effect. PMID- 22312851 TI - [Analytical profile of 1-[3-(3-propoxyphenylcarbamoyloxy)-2-hydroxypropyl]-4-(3 trifluoromethylphenyl)piperazinium chloride]. AB - The purpose of the paper was the completing of the experimentally estimated physicochemical descriptors spectrum of 1-[3-(3-propoxyphenylcarbamoyloxy)-2 hydroxypropyl]-4-(3-trifluoromethylphenyl)piperazinium chloride (labelled as 8e), an effective, highly lipophilic compound against non-tuberculous M. kansasii My 235/80. The identity of the structure 8e was verified by 1Hand 13C-NMR spectral data, IR spectrometry and by elemental analysis as well. The readout from mass spectrometry confirmed an existence of the molecular ion [M + H+]+. The purity of the evaluated compound 8e was checked by absorption thin-layer chromatography, the stability of its aqueous and methanolic solutions was investigated under UV/VIS light. The values of some physicochemical descriptors assigned to 8e, which had been previously published (pKa, log Pexp), were correlated with the constants associated with some antimycobacterially active molecules which are commonly used in therapeutical practice (isoniazid, pyrazinanide, para aminosalicylic acid, ethionamide, streptomycine). For the content determination of the molecule of 8e, RP-HPLC (reversed-phase HPLC) method with an internal standard and UV/VIS spectrophotometry at the wavelength of 238 nm (aqueous medium) and at 244 nm (methanolic medium) were used. PMID- 22312852 TI - [Study of local anesthetics--part 195. Study of micellization of pentacainium chloride in methanol and ethanol solutions]. AB - The critical micellar concentrations of pentacainium chloride in methanol and ethanol solutions with different concentrations were determined by the spectrophotometric method in the UV region of the spectrum at the temperature range of T = 278.15-308.15 K and pH = 4.5-5.0. The dependence of cmc on temperature T turned out to be U-shaped. The influence of the n-alkanols, methanol and ethanol, on the critical micellar concentration was studied. The cmc values show that micelle formation occurred more easily in methanol than in ethanol solutions. Simultaneously the influence of various concentrations of alcohols was studied. The critical micellar concentration rises with an increasing concentration of alcohol up to some value, then cmc decreases. PMID- 22312853 TI - [Medicinal preparations in this country at the end of the 18th century part II- semisolid and solid dosage forms]. AB - This paper links up with Part I and deals with the other medicinal preparations, which were originally included in the Austrian book of prescriptions Dispensatorium pharmaceuticum Viennense and then taken over to the Austrian provincial pharmacopoeia Pharmacopoea austriaco-provincialis, repeatedly published between 1774 and 1794. This part discusses semisolid dosage forms, e.g. Electuaria, Mella, Pulpae, Unguenta, and solid dosage forms, e.g. Emplastra, Extracta, Morsulae, Pilulae, Pulveres, Rotulae, Tabulae, Trochisci. The final part of the paper also lists chemical substances (Chymica et consimilia) prepared in pharmacies and presents general evaluation of the provincial Pharmacopoeia. PMID- 22312854 TI - [Means and methods of acoustic protection in aviation: current status and outlook for development]. AB - Analysis of the current status of acoustic protection in aviation shows that despite the material progress in the field, risk of professional pathologies in flying and technical personnel is still high. The situation is dramatized by the lack of effective personal and crew acoustic protectors. The authors speculate on applicability of innovative materials and technologies, ingenious designs of earphones and modular prefabricated demountable structures. Tests of proposed personal protectors demonstrated their competitiveness with foreign analogs. Prospective lines of development, e.g. incorporation of active sound absorption systems in existing passive protectors are discussed. PMID- 22312855 TI - [Rhythmosuggestive compensation and unconscious mechanisms of regulation]. AB - The article describes rhythm suggestive compensation (RSC), a new method of autonomous crew psychological support based on recruitment of cerebral mechanisms of regulation (psychological defense). The method integrates several ways of optimization such as rhythmic stimulation, binaural drumming and verbal suggestion. Procedure of rhythm suggestive compensation is tailored to each individual person with allowance for actual functional interaction of the brain hemispheres, person specific reaction to suggestive information and psychological defense. Meaningful suggestive patterns are modulated by an algorithm and harmonize with rhythmic sensory stimulation. Hence, the controlled change in activities of the hemispheres and different regions of the brain is combined with the effective form of suggestion. Effectiveness of rhythm suggestive compensation was verified with two groups of participants in combat operations (n=5). Compensatory procedure for Group-1 consisted of a simple combination of rhythmic audiovisual stimulation and verbal suggestion. Effectiveness was evaluated by cerebral potentials evoked by emotionally engaging images. Group-2 was treated with the RSC procedure. RSC was found to outdo rhythmic audiovisual stimulation. In addition, it was shown that regular repetition of the rhythm/suggestive procedures does optimize mental state and builds up a stable mental set. PMID- 22312856 TI - [Style of communication between mission control centers and space crews]. AB - The article deals with a pilot investigation into the audio communication of cosmonauts with ground controllers. The purpose was to verify in space flight the patterns and trends revealed in model tests of intergroup communication, and to pinpoint the signature of multinational crew communication with 2 national mission control centers (MCCs). The investigation employed authors' content analysis adapted to the scenario of long-duration mission. The investigation resulted in a phenomenon of double-loop ground-orbit communication, divergence, difference in opinion predictable from the concept formulated by G.T.Beregovoi. Also, there was a notable difference of expressions used by controllers of 2 MCCs. PMID- 22312857 TI - [Effect of adaptive biocontrol sessions in the presence of strong professional skill]. AB - Effect of adaptive biocontrol on efficiency of the operator possessing stable skills in simulating manual control of Soyuz hang-up and berthing to the International space station (ISS) was studied. Job quality was evaluated by the time, energy and precision parameters. The investigation used an ISS computer model and mock-ups of the board operating controls. PMID- 22312858 TI - [Plasticity of stastocyst inertial mass in terraneous gastropods helix lucorum and pomatias rivulare in altering gravitational field (microgravity, hypergravity)]. AB - Light and scanning electron microscopy was used to study the morphological parameters and ultrastructure of Helix lucorum statocysts and statoliths in Pomatias rivulare statocysts after 56, 93 and 110-day exposure to microgravity aboard the ISS. Increased gravity was simulated by 30-d centrifugation at 6 g. On the first day of recovery, many statoconia and statoliths were found to carry numerous warts. Moreover, statoconia grew in number significantly as compared with the ground control. On the contrary centrifugation caused massive destruction of statoconia. In a month after orbital flight and centrifugation morphology of both statoconia and stastoliths was nearly normal. These results evidence, that the gravitational field is an important factor for the abiotic medium responsible for building up the inertial mass in the equilibrium organ of animals. PMID- 22312859 TI - [Effect of accelerated heavy ions of carbon 12C, neon 20Ne and iron 56Fe on the chromosomal apparatus of human blood lymphocytes in vitro]. AB - Cytogenetic assay of the chromosomal apparatus of human blood lymphocytes was carried out after in vitro irradiation by heavy charged particles with high LET values. Blood plasm samples enriched with lymphocytes were irradiated by accelerated ions of carbon 12C (290 MeV/nucleon and LET = 70 keV/microm), neon 20Ne (400 MeV/nucleon and LET = 70 keV/microm), and iron 56Fe (500 MeV/nucleon and LET = 200 keV/microm) in the dose range from 0.25 to 1 Gy. Rate of chromosome aberrations showed a linear dependence on doses from the densely ionizing radiations with high LET values. Frequency of dicentrics and centric rings in human lymphocytes irradiated by 12C with the energy of 290 MeV/nucleon was maximal at 1 Gy (p < 0.05) relative to the other heavy particles. It was found that relative biological effectiveness of heavy nuclei is several times higher than of 60Co gamma-radiation throughout the range of doses in this investigation. PMID- 22312860 TI - [Effect of the ISS Russian segment configuration on the service module radiation environment]. AB - Mathematical modeling of variations in the Service module radiation environment as a function of ISS Russian segment configuration was carried out using models of the RS modules and a spherical humanoid phantom. ISS reconfiguration impacted significantly only the phantom brought into the transfer compartment (ExT). The Radiation Safety Service prohibition for cosmonauts to stay in this compartment during solar flare events remains valid. In all other instances, error of dose estimation is higher as compared to dose value estimation with consideration for ISS RS reconfiguration. PMID- 22312861 TI - [Evaluation of efficiency of automated analysis of microflora from test-subjects during 7-day dry immersion]. AB - Microbial contamination of integument was evaluated in test-subjects volunteered for 7-day immersion with the purpose to evaluate a technology of automated analysis of human microbiocinosis. Integument microflora was investigated in the baseline data collection period and on day-7 of immersion with the help of the standard bacteriological method and using a prototyped automated analyzer. The investigation showed the possibilities of the automated analyzer to provide operating data about human microflora. PMID- 22312862 TI - [Assay of extracellular low-molecular DNA in blood as a diagnostic technique for clinical and experimental studies]. AB - It was shown experimentally that ionizing radiation and low-frequency noise increase the level of extracelular low-molecular DNA in rat's blood plasma. Growth of this parameter has been observed in acute stroke patients at the onset of the disease. Low-molecular DNA assay is proposed for evaluation of the unfavorable effects of physical factors on organism. PMID- 22312863 TI - [Dynamics of calcium utilization for skeleton formation in Japanese quail embryos under the microgravity condition]. AB - Tibia and femur osteogenesis was studied in embryonic lower limbs developed in microgravity. The maximal difference in ash content of shell in the flight and control groups was registered on days 4, 10 and 14 amounting to 10.27; 9.56 and 12.95% respectively. Shell analysis for calcium showed the largest difference between the groups on day 4 (8.94 mg). However, this difference was not seen already on days 14 and 16. Hence, according to the results of the investigation, although shell calcium utilization and osteogenesis in flight embryos of the Japanese quail were retarded, by the time of hatching the morphological and chemical parameters of the lower limb bones were essentially same as of the ground controls. PMID- 22312864 TI - [Some clinical outcomes of fractional gamma-irradiation of primates]. AB - The investigation with macaque-rhesus males aged 3 to 5 years was aimed at evaluation of the effects of 2 patterns of fractional gamma-irradiation ending up with an equal effective residual dose of 100 sGy. Irradiation was carried out on gamma-ray unit GOBO-60 with a 137Cs source and certified activity of 72 g-eq. Ra. Rectal temperature, heart rate, blood pressure and body mass were followed up over the period of 9 months. Rate of body mass gain in primates irradiated with the total gamma-dose of 250 cSv was lower as compared to the group that received the total dose of 132 cSv. Repeated irradiation 3 months later elevated the body mass gain and elevated rectal temperature considerably only in the primates that had been initially irradiated at 250 cSV Fractional gamma-irradiation had no effect on HR or BP. PMID- 22312865 TI - [Journal "Aerospace and Ecological Medicine" in the content of international science data bases. Aerospace medicine]. PMID- 22312866 TI - [Use of neural networks for recognition of pathological changes in stimulation electromyograms]. PMID- 22312867 TI - [An adaptive complex algorithm for shock heart rhythm recognition and its use in automated external defibrillators]. PMID- 22312868 TI - [A comparative study of the diffusion and axial models of radiation passing through a biological scattering layer based on the Monte Carlo method]. PMID- 22312869 TI - [A device for wireless transmission of electrocardiographic and electroencephalographic data]. PMID- 22312870 TI - [Simulation of transcutaneous wireless infrared transmission of energy]. PMID- 22312871 TI - [An experimental setup for studying wireless inductive-coupling transmission of energy in auxiliary blood circulation systems]. PMID- 22312872 TI - [A conductive biocompatible composite carbon-nanotube material]. PMID- 22312873 TI - [Optical methods for noninvasive blood glucose monitoring]. PMID- 22312874 TI - [ProGraf-7000 X-ray apparatus potentialities for tomosynthesis]. PMID- 22312875 TI - [Spectral density analysis of pulse signal of the radial artery]. PMID- 22312876 TI - ["Medicine of the future is preventive medicine"--N.I. Pirogov]. AB - The role of N.I. Pirogov is shown in the study of infectious factors significance in high mortality during the Crimean war combats. He recommended important organizational, sanitary and therapeutic measures both in war and peacetime conditions. PMID- 22312877 TI - [Immunological aspects of HCV/HIV coinfection]. AB - AIM: To evaluate effects of HCV/HIV coinfection on blood lymphocyte phenotype including cells CD56+. MATERIAL AND METHODS: We studied standard immunogram, subpopulational composition and functional activity of blood cells CD56+ in 67 patients with verified diagnosis of HIV infection and virus hepatitis C. RESULTS: We discovered some pathogenetically sound indices of immune status in patients with HCV/HIV coinfection. Some of the immune shifts detected changed in response to intake of narcotic drugs, antiretroviral treatment, hepatic cirrhosis, pneumonia. CONCLUSION: Parameters of subpopulational composition and functional activity of cells CD56+ in the blood of patients with HCV/HIV coinfection elucidate some unknown features of the above infectious process which should be considered in this coinfection treatment and prophylaxis. PMID- 22312878 TI - [Diagnosis of tuberculous pericarditis in patients with HIV-infection]. AB - AIM: To study specific features of the incidence, course and diagnosis of tuberculosis pericarditis (TP) in patients with HIV-infection. MATERIAL AND METHODS: We analysed results of diagnosis of 304 primary patients with organ tuberculosis in combination with HIV infection treated in Moscow tuberculosis hospital N 7 in 2006-2010. CD4 lymphocyte count median in tuberculosis onset was 140 in 1 mcl, 63.2% patients had a baseline level of CD4 lymphocytes under 200 in 1 mcl. RESULTS: TP incidence in primary patients with tuberculosis and HIV infection was 6.3% while in patients with tuberculosis of multiple locations- 13.7%. Cardiac tamponade symptoms were registered only in one case. Pericardial effusion was classified as moderate and large in 68.4% patients. Patients with large effusion (more than 20 mm in isolation of pericardial leaves) have undergone diagnostic pericardiocentesis and, in some cases, microdrainage. Sensitivity of exudate test for M. tuberculosis DNA with use of polymerase chain reaction was 100%. CONCLUSION: Active surgical policy in massive effusion tuberculosis pericarditis in line with adequate antituberculosis and antiretrovirus therapy in HIV-infected patients results in rapid resorption of the effusion. PMID- 22312879 TI - [Current course of pneumocystic pneumonia in HIV-infected patients]. AB - AIM: To describe clinical and laboratory characteristics of pneumocystic pneumonia (PP) in patients with HIV-infection for improvement of diagnosis quality. MATERIAL AND METHODS: Detailed examination was performed in 111 HIV infected patients with suggested diagnosis of PP. The following investigations were made: clinical, x-ray examinations, total count and biochemical blood tests, enzyme immunoassay, indirect immunofluorescence reaction (II-FR) for Pneumocystis jiroveci antigens in bronchoalveolar lavage fluid (BALF) or induced sputum. For diagnosis of other secondary diseases PCR was used for investigation of BALF and bronchial biopsy to detect DNA of Mycobacterium tuberculosis complex, Candida albicans, Cytomegalovirus, Toxoplasma gondii, Mycoplasma spa., Herpes simplex I, II. DNA of cytomegalovirus in blood was detected with PCR. Microscopic tests of the sputum were conducted for detection of acid-resistant mycobacteria. RESULTS: PP was associated with other secondary diseases in 59% patients (pulmonary tuberculosis ---16%, CMV pneumonia--31%, combination of all the lesions--5%). PP diagnosis was cancelled and pulmonary tuberculosis was diagnosed in 12 patients. In combination of PP with other pathology dominant were symptoms observed in PP monoinfection and only effective anti-pneumocystic treatment revealed signs of comorbid pathology. Tuberculosis patients had weaker signs of respiratory failure, symmetric bilateral interstitial or small-focal alterations were detected less frequently. CONCLUSION: Current PP course characteristics in HIV infection are identified. In clinical diagnosis of PP special attention should be paid to data complex especially to increasing respiratory failure, high ESR, elevated lactate dehydrogenase, low blood pO2, fast response to ex juvantibus therapy. The most effective method of the diagnosis verification--BALF IIFR. PMID- 22312880 TI - [Analysis of lethal outcomes in patients with newly-diagnosed tuberculosis of the respiratory organs in combination with HIV-infection]. AB - AIM: To analyse lethal outcomes in patients with newly-diagnosed respiratory tuberculosis comorbid with HIV-infection depending on initial count of CD4+ lymphocytes. MATERIAL AND METHODS: Of 304 HIV patients with newly-diagnosed tuberculosis treated in Moscow Tubercusis Hospital N 7 in 2006-2010, 40 (13.2%) patients died. Tuberculosis diagnosis was made after detection of M. tuberculosis (MT) by different tests, MT DNA in different biological material, histological verification or by effectiveness of specific antituberculous therapy. Postmortem examinations were made according to the protocol. RESULTS: Significant differences were detected in patients with initial count of CD4+ lymphocytes less than 50 in 1 mcl. Specific CNS affection was found in patients with initial lymphocyte count CD4+ less than 100 in 1 mcl. Most of autopsy examinations registered generalized acutely progressive tuberculosis with multiple lesions of internal organs and lymph nodes (LN). Microscopy revealed obscure morphological picture of specific inflammation with prevalence of alternative-exudative tissue reactions in the absence of a productive inflammation component. Cases with submiliary dissemination which was invisible in macroscopic examination due to a bright picture of exudative tissue reaction (rare plethora of the lungs, alveolar and interstitial edema, perifocal inflammatory reaction of nonspecific reactive nature) and small size of the lesions. The comparison of clinical and autopsy diagnoses revealed that involvement of intrathoracic LN and miliary dissemination, according to autopsy, occurred much more frequently than shown by antemortem standard x-ray examination of the chest. CONCLUSION: It is strongly recommended to perform computed tomography of the chest in all HIV-infected patients with long-term fever but without visible alterations on chest x-ray. PMID- 22312881 TI - [Specific features of lymphoid infiltration in liver biopsy in patients with chronic viral hepatitis B and C]. AB - AIM: To study characteristics of leukocytic infiltration of the liver in patients with chronic viral hepatitis B and C (CVHB and CVHC) with consideration of hepatitis activity and fibrosis severity. MATERIAL AND METHODS: The examination of 37 patients with CVHB (n = 13) and CVHC (n = 24) included liver puncture biopsy by Mengini, subsequent histological and morphological investigation of liver biopsy with immunohisto- and immunocytochemistry. RESULTS: In CVHB and CVHC patients leukocytic infiltrates (LI) of the liver present primarily with T lymphocytes (CD3+), NKT cells (CD3+CD16+CD56+), NK cells (CD16+CD56+), T regulatory lymphocytes (CD4+CD25+), cytotoxic T-lymphocytes (CD8+). Cytotoxic lymphocytes (CD8+) and NK cells (CD16+CD56+) detected in hepatic LI of patients with chronic viral hepatitis are similar in composition with cells in hepatic tissue infiltrates in autoimmune hepatitis. We are the first to detect the complex of T-regulatory cells (CD4+CD25+) in hepatic parenchyma of these patients. This complex suppresses cellular immune response in virus elimination and damaged tissues and supports development of persistent viral infection with autoimmune component. CONCLUSION: The complex of T-regulatory cells (CD4+CD25+) isolated in hepatic LI evidences for existence of a morphofunctional base for autoimmune manifestations in the presence of persistent viral infection. PMID- 22312882 TI - [Markers of intestinal infection agents in patients with acute viral hepatitis with cholestatic syndrome]. AB - AIM: To study the pathogenetic role of agents of the most common intestinal infections in the development of cholestatic syndrome in patients with acute viral hepatitis. MATERIAL AND METHODS: We investigated 97 patients with acute viral hepatitis (AVH), 112 blood donors and 165 patients with acute bacterial intestinal infections (ABII). O-antigens of the major causative agents of infections in feces and serum (CIC) and the presence of antishigatoxic CIC in the serum were found. RESULTS: It is first shown a high incidence of O-antigens of Salmonella, Yersinia, Helicobacter, Shigella and Campylobacter in 81.4% of patients with AVH, more frequent and prolonged their detection in patients with the syndrome of cholestasis, higher total O-antigenic load, the frequent identification of mixed-antigens, high levels of LII in comparison with patients without AVH cholestasis and with acute intestinal infections patients. One-third of patients with AVH revealed antishigatoxic CIC in blood serum, which is lower than in patients with ABII. CONCLUSION: The findings suggest the importance of intestinal infections agents in the development and maintenance of inflammation in the liver, the prognostic value of identifying markers in patients with AVH, especially with the syndrome of cholestasis. PMID- 22312883 TI - [Specific damage to the kidneys in patients with chronic hepatitis C associated with cryoglobulinemia]. AB - AIM: To reveal clinical and morphological characteristics of renal damage in patients with cryoglobulinemia (CGE) associated with chronic viral hepatitis C (CVH-C) for upgrading diagnosis, prognosis and optimization of the treatment methods. MATERIAL AND METHODS: Two groups of CVH-C patients were studied: with CGE (group 1, n = 64) and free of CGE (group 2, n = 62) matched for gender, age and duration of the disease. Biopsy of the liver for assessment of the histological activity index and histological sclerosis index by METAVIR scale was conducted in 63 patients. Of patients with CGE-related damage to the kidneys, 48 were examined for clinical picture with morphological investigation of renal tissue in 15 of them including semiquantitative evaluation of fibrosis degree and activity. RESULTS: Patients with CVH-C and CGE had a wider spectrum of systemic lesions than CVH-C patients without CGE. Only CGE patients demonstrated more severe affection of the skin, joints, kidneys and the nervous system. Therefore, CGE can be considered as a marker of poor prognosis. Liver biopsy showed that CGE patients had more pronounced fibrosis (3-6 points) versus 0-2 points in 80% patients from group 2. Duration of CVH-C from probable infection to renal damage in 48 patients with CGE glomerulonephritis (GN) averaged 197.05 +/- 18.5 months. Renal biopsy diagnosed CGE mesangiocapillary GN in 13 patients and membranoproliferative GN in 2 patients. Patients with HCV infection had a more severe proliferative form of nephritis--mesangiocapillary GN. In 48 GN patients with HCV-infection and CGE, GN ran latently with moderate urinary syndrome in 29 (60.4%) patients, with nephrotic syndrome--in 9 (18.6%), with acute nephritic syndrome--in 10 (21.0%) patients. Most of the patients had arterial hypertension, 13 patients had creatinemia (3.02 +/- 0.55 mg/dl), rapidly progressive GN was diagnosed in 4 patients. CONCLUSION: Persistent CGE marks poor prognosis in CHC patients and is an indication for antiviral treatment to prevent severe organ lesions, first of all of the kidneys. Development of CGE vasculitis with severe damage to the kidneys demands immunosuppressive therapy in combination with plasmapheresis or cryapheresis followed by antiviral drugs. As shown by pilot results, a new approach with rituximab is perspective but further evidence is needed for final conclusions. PMID- 22312884 TI - [Perspectives of prevention and treatment of herpes symplex with regular recurrence]. AB - AIM: To assess efficacy of two-stage treatment of severe genital herpes (GH) with regular recurrences: combined use of antivirus medicines with interferon preparations and its inductors followed by antirecurrence vaccine therapy. MATERIAL AND METHODS: Two-stage treatment was given to 100 patients suffering from GH with severe regular recurrences. One-stage treatment included famvir in combination with interferon (viferon) or interferon inductors (amixin, cycloferon) and antioxidants. Stage two treatment consisted of vaccine therapy of patients who failed prophylactic standard vaccination by allergometric technique. RESULTS: The first stage treatment prolonged recurrence-free period 2-3-fold in more than 85% patients, improved quality of life. Stage-two treatment resulted in long-term clinicoimmunological remission which is necessary for conduction of anti-recurrence vaccine treatment. CONCLUSION: Changes in therapeutic-preventive policy in patients with recurrent GH with regular recurrence (2 stage of treatment) prolong recurrence-free intervals, improve quality of life and social adaptation of patients. PMID- 22312885 TI - [Leptospirosis and its complications]. AB - Leptospirosis (Weil-Vasiliev disease) is a zoonotic natural focal disease running as an acute fever with severe intoxication, lesion of the kidneys, liver, CNS, hemorrhagic syndrome, complications, frequent lethal outcomes. Clinical features of leptospirosis in patients with comorbid diseases are not studied adequately. Lethal outcomes are often caused by such serious complications as infectious toxic shock, acute renal-hepatic failure, massive hemorrhagic syndrome, infectious myocarditis, etc. Two cases of leptospirosis with irreversible complications are reported: one case with severe lesion of the kidneys and heart, and the other case with lethal damage to the kidneys. The evidence for a severe course of leptospirosis complicated with renal insufficiency is provided. Lethal outcomes in leptospirosis are often associated with late diagnosis because of the disease manifestation similarity with such diseases as hemorrhagic fever and renal syndrome. It is shown that leptospirosis runs a very severe cause in exacerbation of preexisting infection or somatic disease. The necessity of consideration of the background pathology demands an early and individual correction of diagnostic algorithms, conduction of etiotropic and pathogenetic therapy, rehabilitation measures. Comorbid diseases in leptospirosis patients have an essential negative effect on leptospirosis clinical picture, on a course of infectious process (aggravation of endogenic intoxication, polyorganic disorders, nonspecific complications). PMID- 22312886 TI - [Implication of functional platelet activity in pathogenesis of Q-fever]. AB - AIM: To ascertain the role of platelets in pathogenesis of clinical symptoms in patients with Q-fever. MATERIAL AND METHODS: We studied hemostasis with estimation of functional platelet activity in 49 patients with Q-fever. RESULTS: Hemorrhagic syndrome (HS) occurred in 34.4% patients with Q-fever (QF) during seasonal rise of morbidity. HS manifested with petechiae (12%), hematomas (32%), nasal bleeding (17%), stomatorrhagia (9%), melena (12%). Characteristics and duration of such symptoms as weakness (100%), myalgia (72%), arthralgia (52.9%) suggested hemocoagulatory disorders as a cause of the symptoms appearance. At the height of the disease thrombocytopenia was accompanied with inhibition of platelet aggregation activity, but regression of the clinical symptoms was associated with an increase in platelet count and platelet hyperaggregation. Fibrinogen content was elevated during hospitalization in 50% patients. CONCLUSION: Clinical manifestations of HS are typical for Q-fever prevalent in the Astrakhan Region. Hemostatic disorders because of altered functional activity of platelets were registered in all the cases and evidence for pathogenetic unbalance of homeostasis in Q-fever patients. PMID- 22312887 TI - [Comparative characteristics of transmissive fevers in the territory of Astrakhan region (clinicoepidemiological evidence)]. AB - Epidemiologists register a trend in the latest decades for expansion of the areas of natural-focal transmissive fevers morbidity in the Astrakhan region. This is explained by reconfiguration of natural landscapes as a result of increasing anthropogenic impact. The Astrakhan territory exclusively contains 4 types of landscape with evolutionally formed several natural foci of transmissive fevers: Crimean hemorrhagic fever, West Nile fever, Astrakhan rickettsial fever, Q-fever. Early diagnosis of these diseases determines further treatment, prophylactic policy in the infection focus. PMID- 22312888 TI - [Pneumonia or drug-related exogenic allergic alveolitis? Key role of anamnesis in differential diagnosis]. AB - A case is reported of an old female patient with exogenic allergic alveolitis which was first diagnosed as pneumonia progressing in the presence of long-term and intensive antibiotic treatment. Detailed analysis of the case history gave grounds for suspected drug-related exogenic allergic alveolitis. Discontinuation of antibiotics, administration of glucocorticoids and antiplatelet drugs led to recovery. PMID- 22312889 TI - [Food allergy]. AB - Food allergy (FA)--a condition of high sensitivity to food products--is widely spread allergic disease treated by allergologists, gastroenterologists, dermatologists, physicians, pulmonologists. FA pathogenesis involves immunological mechanisms with participation of immunocompetent cells and production of IgE and IgG. Treatment aims at elimination of causative antigen. Proteins of cow milk, hen's eggs, cereals, fish, citrus fruit, nuts, tomatos are most common such antigens. It is especially important for infants. FA manifests with anaphylactic shock, oral allergic syndrome, respiratory symptoms, abdominal impairments. The digestive system is both a target and a course of FA formation. FA arises mostly because of defects of gastrointestinal immune system, inability to synthetize IgA in adequate quantity while IgA has protective properties. Therefore, FA treatment should include probiotics, cytoprotectors, enzymes, sorbents. Atopic dermatitis, one of FA manifestations, is treated with non hormonal drugs containing lipids, urea, topic inhibitors of calcinevrin. On demand, topic glucocorticosteroids, sometimes in combination with antimicrobial and antifungal drugs are added. Multidisciplinary approach to FA problem gives positive results. PMID- 22312890 TI - [Antiretrovirus drugs impair kidneys in HIV-infection]. AB - Renal damage in HIV infection may result from direct action of HIV and from other causes including nephrotoxic action of medicines. HIV-infected patients receive a wide spectrum of medicines and can be placed in a risk group of drug-induced damage to the kidneys. Risk of nephrotoxicity should be considered in administration of antiretrovirus drugs in HIV patients. Strategy of preventive measures in relation to pharmacological harm to the kidneys consists in early detection of patients with high risk and correction of modifiable risk factors. PMID- 22312891 TI - [Experience with rituximab treatment (monoclonal antibodies to B-lymphocyte CD20 receptors) of Wegener's granulomatosis patients with renal impairment]. AB - AIM: To assess efficacy of rituximab in patients suffering from Wegener's granulematosis (WG) with renal disease. MATERIAL AND METHODS: We analysed clinical laboratory data from 9 WG patients with renal disease treated with rituximab in E.M. Tareev clinic. RESULTS: The treatment led to a complete remission in 7 (77.8%) patients, a partial remission--in 2 (22.2%) patients. Vasculitis activity regressed including renal damage (a decrease of 24 h proteinurea, enhanced glomerular filtration rate). A prednisolone dose decreased from 38.3 to 10 mg/day (to month 6) and to 7.5 mg/day (to month 12). Non selective cytostatic drugs were discontinued in all the patients. Recurrences occurred in 3 (33.3%) patients, one with lethal outcome after 6 months of rituximab administration, in two cases one more course of rituximab produced another complete remission. Serious side effects were absent. CONCLUSION: Rituximab demonstrated high efficacy in the treatment of WG with renal affection resistant to standard therapy, in multiple side effects of standard immunosuppressive therapy and recurrent course. Rituximab help overcome steroid dependence even at late stages of the disease. PMID- 22312892 TI - [From classificational medicine to clinical medicine (the end of the XVIII century to 1870s). Communication 3. The second stage of clinical medicine development: introduction of methods of laboratory experiment and chemical analysis]. AB - The article concerns the end stage of clinical medicine establishment covering the period from early 1840s to the middle 1870s of the XIX century. Basic scientific achievements related to introduction into practical medicine of the methods of laboratory experiment and chemical analysis are reviewed. PMID- 22312893 TI - [The population structure of Mycobacterium tuberculosis in Mongolia as assessed using large sequence polymorphism analysis]. AB - 112 strains of M. tuberculosis isolated from lung tuberculosis patients in Mongolia were genotyped using RD9, RD7, TbD1, RD105, and RD750 loci. The genotypes of all the strains studied were characterized using the conservation of RD7, RD9, and RD750 loci and the presence of the deletion in the locus TbD1. RD105 was detected in 65 isolates (58%). The isolate was classified into two groups--East-Asian and Euro-American. PMID- 22312894 TI - [An algorithm for identification of CTX-M-type beta-lactamase genes using restriction fragment length polymorphism analysis of PCR-product]. AB - The algorithm of the identification of the bla(CTX-M) genes coding CTX-M-type beta-lactamases providing resistance to cephalosporins III-IV was developed. This algorithm provides identification of 49 genes of 96 genes presented in the GenBank database so far. Remaining 47 genes can be identified as consisting of small sub-groups composed of 2-6 genes with the exception of sub-group of the bla(CTX-M-14)-like genes composed of 13 genes. The identification of the bla(CTX M) genes is based on two-step restriction fragment length polymorphism analysis of 544 bp PCR-product (PCR-RFLP). In the first step, determination of subtype (cluster) of the bla(CTX-M) gene occurred using the restriction nuclease Alu I: cluster 1, -2, -8, -9 or -25. Moreover, four genes can be identified just at this step: bla(CTX-M)-59, (cluster 2); bla(CTX-M-63) (cluster 8), bla(CTX-M-45) (cluster 9), and bla(CTX-M-78) (hybrid gene between cluster 2 and cluster 25). At the second step gene identification goes on inside of each cluster separately using a set of 26 restriction nucleases. As a result of the PCR-RFLP-analysis, 23 bla(CTX-M) genes can be identified at the cluster 1, 11 genes--at the cluster 2, 4 genes--at the cluster 8, 9 genes--at the cluster 9, 1 gene--at the cluster 25, and 2 hybrid genes: bla(CTX-M-78) (between clusters 2 and 25), and bla(CTX-M-64) (between clusters 1 and 9). The described algorithm was used for identification of the blac(CTX-M) genes (n = 585) detected in Enterobacteriaceae nosocomial isolates (n = 877), collected from Russial hospitals in 2003-2007. It was shown that major genes belonged to cluster 1 (n = 543), namely--bla(CTX-M-15) gene (n = 515), bla(CTX-M-3) (n = 25), bla(CTX-M-22) (n = 1), bla(CTX-M-23) (n = 1), and bla(CTM-34) (n = 1). Moreover, the genes atributed to cluster 2 were identified: bla(CTX-M-2) (n = 1), and bla(CTX-M-5) (n = 4); and genes belonged to cluster 9: bla(CTX-M-9) (n = 2), and bla(CTX-M-14) (n = 35). PMID- 22312895 TI - [Phylogenetic analysis of symbiotic genes of nodule bacteria in the plants of the genus Lathyrus (L.) (Fabaceae)]. AB - The comparative analysis of the symbiotic genes nifD, nifH, nodA of wild-growing Lathyrus L. species (Fabaceae) connected by genes sequences of 16S aRNA to Rhizobium leguminosarum bv. viceae, Rhizobium tropici, Agrobacterium sp., and Phyllobacterium sp. was carried out. It was demonstrated that all tested genes of strains taken for analysis had high degree of homology with analogous genes of Rhizobium leguminosarum bv. viceae. It was suggested that symbiotic genes were introduced into Rhizobium tropici, Agrobacterium sp., and Phyllobacterium sp. strains by means of horizontal gene transfer over from Rhizobium leguminosarum bv. viceae strain. The recombinant strains were formed, capable to nodulate Lathyrus L. species that earlier was not considered characteristic for these plants. PMID- 22312896 TI - [Entification of the Rubella virus genotype 1H in Western Siberia]. AB - Molecular epidemiological study of novel strain of Rubella virus isolated during the outbreak in Western Siberia in 2004 was described. Detailed phylogenetic analysis performed based upon entire SP-region, which encodes all three Rubella structural proteins (C, E2, and E1), was implemented. This analysis provides characterization of this strain and classifies it as 1H genotype, thereby correcting previous classification of this strain based upon shorter nucleotide sequence, only encoding E1 protein. Therefore, this study identified the genotype of the Rubella virus not previously detected in Western Siberia (and even entire Russian Federation), which highlights the importance of more extensive characterization of genetic variability of the Rubella virus, especially with regard to potential influence of vaccination on the Rubella virus mutagenesis. PMID- 22312897 TI - [Genetic variability of isolates of pandemic influenza A virus H1N1 isolated in Russia in 2009]. AB - Complete nucleotide sequence of the genome segments encoding the surface glycoproteins, hemagglutinin, and neuraminidase of influenza A virus H1N1 derived from the patients with influenza in the context of pandemic (H1N1) 2009 was determined out of 14 isolates of pandemic influenza. The philogenetic analysis of these sequences demonstrated their genetic similarity to the corresponding genes of the pandemic influenza virus A (H1N1) 2009 isolates obtained in other countries; each gene homology was greater than 99%. Neuraminidase mutations causing virus resistance to oseltamivir and other neuraminidase inhibitors, known from the literature, were not detected. The hemagglutinin gene mutation D222G was found in 4 isolates from autopsy material. In the hemagglutinin of pandemic A/Salekhard/01/2009(H1N1) isolate a mutation G155E leading to the increase in viral replication in developing chick embryos was detected. The nature and frequency of nucleotides substitutions within HA and NA genes were determined in the current research. PMID- 22312898 TI - [Genome composition analysis of the reassortant influenza viruses used in seasonal and pandemic live attenuated influenza vaccine]. AB - The cold-adapted, temperature sensitive and attenuated influenza master donor viruses A/Leningrad/134/17/57 (H2N2) and B/USSR/ 60/69 were used to generate the vaccine viruses to be included in live attenuated influenza vaccine. These vaccine viruses typically are 6:2 reassortant viruses containing the surface antigens hemagglutinin and neuraminidase of current wild type influenza A and influenza B viruses with the gene segments encoding the internal viral proteins, and conferring the cold-adapted, temperature sensitive and attenuated phenotype, being inherited from the master donor viruses. The 6:2 reassortant viruses were selected from co-infections between master donor virus and wild type viruses that theoretically may yield as many as 256 combinations of gene segments and thus 256 genetically different viruses. As the time to generate and isolate vaccine viruses is limited and because only 6:2 reassortant viruses are allowed as vaccine viruses, screening needs to be both rapid and unambiguous. The screening of the reassortant viruses by RT-PCRs using master donor virus and wild type virus specific primer sets was described to select both influenza A and influenza B 6:2 reassortant viruses to be used in seasonal and pandemic live attenuated vaccine. PMID- 22312899 TI - [Characterization of the H5N1 influenza virus isolated during an outbreak among wild birds in Russia (Tuva Republic) in 2010]. AB - The study of basic biological properties of H5N1 subtype strain isolated during an outbreak among wild birds in Russia in 2010 was presented. The study was carried out using conventional methods according to the WHO recommendations. H5N1 influenza virus isolated in Siberia belonged to clade 2.3.2 of the hemagglutinin gene; the phylogenetic analysis was performed. The antigenic characteristics and the basic genetic markers of biological properties were studied. It was shown that all strains were highly pathogenic for chickens and white mice. Thus, it was shown that in Russia in the 2010 H5N1 virus phylogenetically closely related to Asian variants caused epizootic among wild birds. The potential danger of this variant of the virus for humans was confirmed by different methods. We discussed the possibility of formation of H5N1 influenza natural focus. PMID- 22312900 TI - [The information theory of brain systemic activity]. AB - Information equivalents of initial requirements and their satisfaction are shown to induce formation of discrete information systemoquanta of psychic activity on morphofunctional structures of the action result acceptor in the course of build up of cerebral archtectonics of the functional systems governing the behaviour and psychic activity. Consecutive stages of induction of information systemoquanta of action result acceptors are described. Predominant motivations are supposed to play the leading role in the psychic activity through their involvement in the induction of information systemoquanta and their retrieval from memory. The role of emotions in the subjective information estimation of systemic cerebral activity is considered. It is argued that parameters of achievement of adaptive results by a subject are imprinted on acceptor structures via reverse afferentation in the form of specific information images. Enrichment of action results acceptors with information and extraction of information systemoquanta by prevailing motivations are believed to make up the basis of consciousness and thinking. The hypothesis of holographic organization of acceptors of the results of systemic brain action is considered. PMID- 22312901 TI - [Genetic study of predisposition to community-acquired pneumonia]. AB - The study included 243 patients with acute community-acquired pneumonia and 173 healthy subjects. The following candidate loci were used to investigate genetic variability: 3 sites of CYP1A1, GSTM1, GSTT1, GSTP1, ACE gene of the rennin angiotensin system, chemokine receptor gene CCR5. Enhanced predisposition to pneumonia was shown to be characteristic of homozygotes in deletion at the ACE locus (OR = 1.8; p = 0.013), carriers of normal alleles of the GSTM1 locus (OR = 1.7; p = 0.010), and homozygotes in allele 606T of the CYP1A1 gene (OR = 1.6; p = 0.020). PMID- 22312902 TI - [Athrombogenic activity of endothelium in patients with cerebral complications of hypertensive disease and concomitant coronary heart disease]. AB - This study of antiaggregative and anticoagulant activities of endothelium included 90 patients with cerebral complications of hypertensive disease and coronary heart disease in the acute and early rehabilitation period after ischemic stroke. The study revealed paradoxical prothrombotic activity of endothelium and compromised antithrombotic potential of the vascular wall. PMID- 22312903 TI - [Hemodynamic disorders and myocrdial insufficiency after toxic doses of propranolol]. AB - Results of an experimental study of the toxic action of propranolol on the cardiovascular system are presented. It was shown that i/p injections of propranolol (2 mg/100 g) cause circulatory insufficiency, activate free radical oxidation, and induce cardiac dysfunction. PMID- 22312904 TI - [Modulation of membrane blebbing and microparticle sheddimg as a target of cardiovascular prophylaxis]. AB - Physicocemical and antigenic properties of peripheral blood lymphocytes and shed membrane microparticles were studied in patients with CHD and angina of effort and in those with hypertensive disease. The frequency of lymphocyte blebbing in CHD and angina patients was significantly higher than in those with HD (70.56, 52, 25.7% respectively). Incubation with rotenone and zymosan resulted in an increase of lymphocyte blebbing to 77.34 and 86.5% vs the initial level of 70.56% (p < 0.05). Patients of both groups had an increased number of membrane microparticles in peripheral blood (59.6 and 78.2 U/4 cm2 respectively). It is concluded that modulation of Imphocyte blebbing and microparticle shedding may be a promising target of cardiovascular prophylaxis. PMID- 22312905 TI - [Investigation of lymphocytes activation using a method of coherent phase microscopy]. AB - Investigation of initial stages of T-lymphocytes activation was performed by coherent phase microscopy (CPM) based on the measurements of phase thickness and diameter of the cell and its organelles. Lymphocytes where activated in two ways: by addition of 2 10-6 g/ml phytohemagglutinin (PHA) and with He-Ne laser (lambda = 633 nm, 10-3 W) radiation. It was shown that phase thickness is proportional to refractivity (difference between refractive indices of an object and the surrounding medium) and geometrical thickness. Phase thickness decreased during activation independently of the nature of the stimuli. Phase thickness in healthy donors was 220 + 60 nm; decreased to 110 + 30 nm 1 h after addition of PHA. The same values were achieved 30 min after stimulation with the He-Ne laser. Characteristic changes in phase thickness in the nucleus and nucleolus were observed after lymphocytes were stimulated with the laser. PMID- 22312906 TI - [Purinergic P2-receptors as potential targets of new pharmaceutical products]. AB - P2-receptors are widespread in animal and human organs and tissues. Therefore, they attract much attention as potential targets of new drugs. This article presents in brief characteristics of P2 receptors and reviews the author's search for new antagonists of P2-receptors as well as his studies on the role of ectonucleotidases and unique temperature-dependence of P2 receptor activity. In addition, the presence and functional activity of P2 receptors in human uterus, fallopian tubes, heart and blood vessels are described. The possible physiological and pathophysiological role of P2 receptors in these tissues, as well as prospects for the development of drugs acting via P2 receptors is discussed. PMID- 22312907 TI - [Irina Nikolaevna Blokhina, member of the Russian Academy of Medical Sciences]. PMID- 22312908 TI - [The glucose, glycotoxins and glycation products: the involvement into pathogenesis of microangiopathies, arteriolosclerosis and atherosclerosis]. AB - The hyperglycemia and diabetes and the concurrent increase of glucose's chemical glycation of (GLU) circulating and structured proteins are the conditions of occurring of various a physiological (GLU) metabolism processes: a) a polyolic way with the synthesis in cells' cytosol of sorbitol alcohol, organic osmolit producing hyperosmolarity of cytosol; a galactosamine way of GLU transformation leads to aminoglycotoxins' formation; the intensification of hexose transformation into trioses leads to the increase of synthesis and accumulation of glycotoxins of glyoxal and methylglyoxal in intercellular medium. The reaction of proteins' glycation, proportionally to the magnitude and duration of hyperglycosemia, results in sequential formation of Shiff bases, Amadori products and glycation end products. The glycation of proteins with glycotoxins results in the immediate formation of glycation end products. The derangement of biologic function of endoecology is determined by the accumulation in the intercellular medium of GLU which factually is a biologic "refuses" with lesser molecular mass; and the glycation end products becomes greater biologic "refuses". The disorders of GLU metabolism results informing of destructive inflammatory processes in the wall of muscular type arterioles, postarterioles, capillaries and venules--the vessels of microcirculatory component of circulatory system with the development of diabetic microangiopathies in various internal organs. The increase of endothelium thickness narrows the lumen of arterioles and capillaries intensifying the peripheral resistance to blood flow. The glycotoxins as bi functional reagents form the cross-links in collagen fibers of areolar tissue enhancing the hardness of vessels' walls, the pericytes' malfunction, and increasing the velocity of pulse wave conduction. The tissue fixed glycation end products--the large endogenous phlogogens can be utilized only in citu under the realization of extracellular proteolysis, the activation of oxidation by O2 active forms and the biologic reaction of inflammation--phagocytosis by macrophages, the functional phagocytes. The surplus of GLU can be removed by the biologic reaction of excretion. The extracellular proteolysis forms the soluble fragments of glycation end products which in the intercellular medium bind the soluble fragments of receptors of macrophages. Under diabetes, it is reasonable to monitor in blood plasma the content of both GLU and such glycotoxins as glyoxal, methylglyoxal and malonic dialdehyde. PMID- 22312909 TI - [The content of nitrite and N-nitroso compounds of plasma as a diagnostic test of nonspecific inflammation]. AB - The authors' enzymatic sensor was applied to identify the content of nitrite and nitroso compounds of blood plasma in normal condition and under various inflammatory diseases. It is established that in normal conditions blood plasma contains nitrite, N-nitroso compounds (RNNO) and S-nitroso compounds (RSNO) in concentrations less than 100 nm. The plasma pool of nitroso compounds includes basically thiolferous nitrosate ferrum complex in concentration 3-20 microm. The concentration of nitrite in plasma is from 10 to 150 microm. The concentration (nitrite+RNNO) increases dramatically under inflammatory diseases. This indicator was 0.3-1.0 microm in examined patients with acute and chronic pancreatitis, cholecystitis, ENT diseases of inflammatory character and ARD. In the case of acute appendicitis the indicator reached 10 micro. In case of successful treatment the content (nitrite+RNNO) decreased to the concentration lower than 100 nm. The content of other nitrite and N-nitroso compounds had no reliable variations. Because of this, largely implemented evaluation of intensity of nitric oxide production by the aggregate indicator of nitrites content (NO(x)) in blood seems ambiguous. The reason is that in normal conditions nitrite is presented in trace amount and considerable quantity of nitrate can enter the organism in an exogenous way. Besides that the content of nitrite can depend on kidneys filterability. At the same time, based on the obtained data, the content (nitrite+RNNO) in plasma in concentrations higher than 150 nm are definitely to be considered as pathology. PMID- 22312910 TI - [The age-related aspects of changes in hormones' level in hypophysis-thyroid and hypophysis-gonads systems in residents of Arkhangelsk]. AB - The male permanent residents of Arkhangelsk were examined during the period of daylight hours minimal duration for the purpose to determine the age-related changes in hormones' level. In the age group of 36-45 years the level recession of progesterone, cortisol and testosterone free fractions against the background of broadening towards higher standard limit of fluctuations of steroid-binding beta-globulin level was demonstrated. In the age group of 46-60 years the rise of cortisol level and tendency to level recession of free thyroxin under thyrotrophic hormone level increase was registered. The hypophysial regulation consisted in lutropin and prolactin level lowering at the age of 36-45 years and in rise of thyrotrophic hormone level at the age of 46-60 years. PMID- 22312911 TI - [The detection of vitamin D3 deficiency in preschoolers and schoolchildren of Moscow and St. Petersburg]. AB - The evaluation of prevalence and intensity of vitamin D3 deficiency in preschoolers and schoolchildren residing in Moscow and St. Petersburg was implemented. It is established that 63.6% of all Moscow children and adolescents of and 43% of St. Petersburg minors live in conditions of vitamin D3 deficiency. Regardless of the residence region, the vitamin D3 deficiency prevalence is more typical for schoolchildren as compared with preschoolers. The higher prevalence of vitamin D3 deficiency demands to change the policy of vitamin D3 supply among minors. PMID- 22312912 TI - [The current clinical laboratory in the public health system and medical science: a lecture]. AB - The analytic and diagnostic possibilities of current clinical laboratories are discussed. The roles of laboratory information in the formation of new research directions are characterized. The proposals on the development of economic basics of the development of laboratory medicine. PMID- 22312913 TI - [The clinical laboratory evaluation of accuracy of portable glucometers "Satellite Express" and "Satellite Express mini"]. AB - The portable glucometers "Satellite Express" and "Satellite Express mini" were applied during 35 days to analyze 200 blood samples of patients with diabetes mellitus type I and II and of healthy people. The results were compared with the data of reference analyzer The results of clinical laboratory trials revealed that these glucometers have enough degree of accuracy detection of glucose in capillary blood - 100% of results are within the permissible limits as directed by ISO 15197:2003. Furthermore, 98.3% of results are within the limits of +/- 15% from reference analyzer results. Thereby, the glucometers "Satellite Express" and "Satellite Express mini" can be recommended to detect the glucose concentration in capillary blood for the purpose of glycaemia level self-control by patients with diabetes mellitus. The devices can also be used by medical personnel for express diagnostics in case of emergency care. PMID- 22312914 TI - [The electrophoretic cell analysis applying the instrument complex "Cito expert"]. AB - The electric discharge of living cells and Z-potential of cell membrane are among the most important indicators to determine at cell level the homeostasis of any living organism, including organs and tissues. The cell electrophoresis is considered as the most handy, accurate and reliable practical technique to determine these indicators. The authors developed the first national serial instrument complex for cell electrophoresis. The device differs from international models by using the alternating electric field and original electrophoretic camera. The instrument complex is protected by patents and permits to determine the cells' oscillation amplitude in alternating field proportional to their effective charge. The device also determines the portion of active cells and their distribution according amplitudes and the asymmetry and excess of this distribution. The duration of single analysis consists 5-8 min and the volume of cell suspension is 40 microL. The analysis is applied to 100-300 cells and the voltage is about 10-30 V on the camera electrodes. The instrument complex is most prospectively applied to diagnose and monitor the treatment of critical conditions with intoxication, to express-control the toxicity of various liquid mediums and biologic activity of nano-materials on cell level and to screening promptly the pharmacologic substances and pharmaceuticals. The published nowadays results of studies performed on different devices, permit to expand significantly the sphere of practical and scientific application of cell electrophoresis. PMID- 22312915 TI - [The means of improvement of urine bacteriologic analysis]. AB - The article outlines the information on the etiology of urinary tracts infections, the diagnostic methods and the detection of sensitivity to antiinfection pharmaceuticals of bacteria isolated from urine. In the last 20 years, the criteria of assessment of clinical significance of urinary tracts bacterial infections are refined. Also, the methodic base and arsenal of means of urine bacteriological analysis improved drastically. These changes are to be implemented in the national laboratory practice. PMID- 22312916 TI - [The application of cobaltferous markers in serodiagnostic assay of infectious diseases]. AB - The study was targeted to the investigation of possibilities of using in immunological analysis the sols on basis of bivalent cobalt compounds as a catalytic marker to ensure the trusted visual registration of analysis results in immunology reactions plats. The results of comparative evaluation of immune enzyme and immune catalytic tests on the basis of several commercial diagnostic test systems of various national manufacturers are presented. The conclusion is derived that by the sensitivity and specificity the cobaltferous immunosols are not inferior to immuneperoxidase conjugated metabolites and even have an advantage due to the relative simplicity of immunosol preparation and the possibility of trusted non-instrument registration of results. The application of cobaltferous immunosols permits to develop the diagnostic test systems with trusted visual registration of results following the "yes-no" principle to ensure the immunodiagnostics in poorly equipped laboratories. PMID- 22312917 TI - [The evaluation of thymus function on the basis of circular DNA estimation technique]. AB - The production of T-lymphocytes by thymus is an important indicator of functioning of immune system. The article discusses one of the actual techniques of evaluation of productive function of thymus i.e. qualitative analysis of intracellular circular DNA of T-cells of peripheral blood (TREC). The stages of adaptation of technique on the basis of nationally produced reagents and instruments. To assure the implementation of qualitative polymerase chain reaction a pair of primers with specific sequence of marker of recent thymus emigrants was selected. The optimization of temperature regimen of amplification was made. To ensure the transition to the qualitative analysis on the basis of polymerase chain reaction technic in real-time a fluorescent probe complementary to amplicone nucleotide sequence was developed. The following analytic characteristics of technique were established: sensitivity 4 ng/ml, reproducibility 1.8%. The valid discrepancy of TREC concentrations in patients of different age groups is demonstrated. PMID- 22312918 TI - [The standardization of technique of detection of blood cells cytokine production ex vivo]. AB - The standardized technique to detect the blood cells cytokine production ex vivo was developed. The complex of mitogens of phytohemagglutinin P, phytohemagglutinin M, lipopolysaccharide, concanavalin A is applied to provide the mitogen activation. This approach permits to activate the different types of immunocompetent cells and to induce the secretion of cytokine representative series. It is demonstrated that the application of this technique permits to receive the reproducible results of the secretion of cytokine following the standard procedure. The standard values of spontaneous and mitogene-induced production of cytokines by blood cells of healthy human are determined. PMID- 22312919 TI - [The analytic and diagnostic characteristics of the national test system detecting cyclic citrullinated peptide antibodies]. AB - The clinical signifcance of serodiagnostic assay of rheumatoid arthritis increased nowadays. This is a reason to include the citrullinated antigens' antibodies into the new criteria of diagnostics ACR/EULAR 2010. The approbation of national test system detecting the cyclic citrullinated peptide antibodies was implemented. The analysis was applied to 211 blood serum samples taken of 50 blood donors, 60 patients with rheumatoid arthritis, 66 patients with other rheumatoid diseases. In addition, 35 samples were concurrently analyzed with the comparative test system (CCP2 Euroimmun, Germany). The referential meanings of standard limits were established on the basis of results of study of samples taken from healthy blood donors. When the standard limit was less than 10 arbitrary units the sensitivity made up 75% and the specificity--87.9%. In the case of higher values of citrullinated antigens' antibodies which are more than 15 arbitrary units, the sensitivity made up 68% and the specificity--93.1%. The results of comparing with the comparative test system characterized by high convergence made up 94% (33 out of 35), but the comparative test system detected citrullinated antigens' antibodies in 2 samples. The positive qualitative results of both methods analysis of autoantibodies weakly correlated with one another (r = 0.14). The results testify that the parameters of national test system correspond to the publication data concerning the second generation methods of cyclic citrullinated peptide antibodies detection though yield to the best foreign analogues. PMID- 22312920 TI - Validation of a pediatric vocal fold nodule rating scale based on digital video images. AB - OBJECTIVES: We sought to create a validated scale of vocal fold nodules in children, based on digital video clips obtained during diagnostic fiberoptic laryngoscopy. METHODS: We developed a 4-point grading scale of vocal fold nodules in children, based upon short digital video clips. A tutorial for use of the scale, including schematic drawings of nodules, static images, and 10-second video clips, was presented to 36 clinicians with various levels of experience. The clinicians then reviewed 40 short digital video samples from pediatric patients evaluated in a voice clinic and rated the nodule size. Statistical analysis of the ratings provided inter-rater reliability scores. RESULTS: Thirty six clinicians with various levels of experience rated a total of 40 short video clips. The ratings of experienced raters (14 pediatric otolaryngology attending physicians and pediatric otolaryngology fellows) were compared with those of inexperienced raters (22 nurses, medical students, otolaryngology residents, physician assistants, and pediatric speech-language pathologists). The overall intraclass correlation coefficient for the ratings of nodule size was quite good (0.62; 95% confidence interval, 0.52 to 0.74). The p value for experienced raters versus inexperienced raters was 0.1345, indicating no statistically significant difference in the ratings by these two groups. The intraclass correlation coefficient for intra-rater reliability was very high (0.89). CONCLUSIONS: The use of a dynamic scale of pediatric vocal fold nodule size most realistically represents the clinical assessment of nodules during an office visit. The results of this study show a high level of agreement between experienced and inexperienced raters. This scale can be used with a high level of reliability by clinicians with various levels of experience. A validated grading scale will help to assess long-term outcomes of pediatric patients with vocal fold nodules. PMID- 22312921 TI - Histopathology of the temporal bone in a case of superior canal dehiscence syndrome. AB - OBJECTIVES: We describe the histopathologic findings in the temporal bones of a patient who had, during life, received a diagnosis of superior canal dehiscence (SCD) syndrome. METHODS: The patient was found to have SCD syndrome at 59 years of age. She became a temporal bone donor, and died of unrelated causes at 62 years of age. Both temporal bones were prepared in celloidin and examined by light microscopy. RESULTS: The patient developed bilateral aural fullness, pulsatile tinnitus, and difficulty tolerating loud noises after minor head trauma at 53 years of age. The symptoms were worse on the right. She also had Valsalva induced dizziness and eye movements, as well as sound-induced dizziness (more prominent on the right). Audiometry showed a small air-bone gap of 10 dB in the right ear. Vestibular evoked myogenic potential testing showed an abnormally low threshold of 66 dB on the right, and a computed tomography scan showed dehiscence of the superior canal on the right. Histopathologic examination of the right ear showed a 1.4 x 0.6-mm dehiscence of bone covering the superior canal. Dura was in direct contact with the endosteum and the membranous duct at the level of the dehiscence. No osteoclastic process was evident within the otic capsule bone surrounding the dehiscence. The left ear showed thin but intact bone over the superior canal. Both ears showed focal microdehiscences of the tegmen tympani and tegmen mastoideum. The auditory and vestibular sense organs on both sides appeared normal. No endolymphatic hydrops was observed. CONCLUSIONS: The findings were consistent with the hypothesis put forth by Carey and colleagues that SCD may arise from a failure of postnatal bone development, and that minor trauma may disrupt thin bone or stable dura over the superior canal. PMID- 22312922 TI - Novel use of a suction-irrigation device to remove impacted blood clot from the airway. AB - OBJECTIVES: We sought to describe the novel use of a suction-irrigation device to remove a large blood clot that was causing critical obstruction of the trachea and main stem bronchi in our patient. METHODS: A large-bore suction-irrigation device designed for use in gynecologic cases was adapted for use in removal of an obstructing blood clot in the face of patient decompensation after several unsuccessful attempts at removal with standard otolaryngological instruments. RESULTS: The tracheal obstruction and the significant bronchial obstructions were successfully removed with the suction-irrigation device. The patient's ventilatory status quickly stabilized. He was extubated the following day and discharged home. CONCLUSIONS: The suction-irrigation device proved highly successful in removing a large blood clot from the airway. A similarly designed device made specifically for the airway could prove useful in similar cases in the future. PMID- 22312923 TI - Functional outcomes after lateral crural J-flap repair of external nasal valve collapse. AB - OBJECTIVES: We evaluated the lateral crural J-flap technique in the surgical repair of external nasal valve collapse with standardized and validated outcome measurements. METHODS: Prospective data were gathered on consecutive cases, performed by a single surgeon between 2007 and 2010, of adult patients who underwent a lateral crural approach to repair of external nasal valve collapse. Data were collected on diagnosis, surgical outcomes, and complications. Outcome measures included the Nasal Obstructive Symptom Evaluation and the Rhinoplasty Outcome Evaluation. RESULTS: Fifteen patients were included in the study. Their follow-ups ranged from 9 to 13 months. All patients had statistically significant improvements in Nasal Obstructive Symptom Evaluation scores. There was no significant change in perceived nasal appearance after surgery as measured by the Rhinoplasty Outcome Evaluation. There were no surgical complications. CONCLUSIONS: The lateral crural J-flap approach to repair of external nasal valve collapse is a technically straightforward and relatively safe procedure. The efficacy is excellent at the 1-year follow-up examination. PMID- 22312924 TI - Endoscopic assessment of vocal fold movements during cough. AB - OBJECTIVES: Little is known about the function of the true vocal folds (TVFs) during cough. The objective of this study was to determine the reliability of measuring TVF movements during cough and to obtain preliminary normative data for these measures. METHODS: Sequential glottal angles associated with TVF adduction and abduction across the phases of cough were analyzed from laryngeal videoendoscopy records of 38 young healthy individuals. RESULTS: The intraobserver and interobserver reliability of 3 experienced measurers was high (intraclass correlation of at least 0.97) for measuring sequential and maximum glottal angles. The TVF abduction velocity during expulsion was significantly higher than the precompression adduction velocity (p = 0.002), but there were no significant differences in maximum angle. No statistically significant differences were seen in maximum TVF angle and velocity when they were compared between the sexes and between the levels of cough strength. True vocal fold closure following expulsion occurred in 42% of soft coughs and in 57% of moderate to hard coughs. CONCLUSIONS: The TVF abduction angles during cough can be reliably measured from laryngeal videoendoscopy in young healthy individuals. The TVF movements are faster for expulsion abduction than for precompression adduction, but the extents of abduction are similar. To validly determine the cough phase duration, simultaneous measures of airflow are needed. PMID- 22312925 TI - Chest wall kinematics during speech breathing in tracheoesophageal speakers. AB - OBJECTIVES: The purpose of the present study was to determine how tracheoesophageal (TE) speakers manipulate the chest wall (rib cage and abdomen) to speak and how respiratory compromise (chronic obstructive pulmonary disease; COPD) and task variables influence those behaviors. METHODS: The chest wall movements of 11 male TE speakers (5 with COPD and 6 without COPD) were measured during tidal breathing, spontaneous speech, and reading. Repeated-measures multivariate analyses were used to compare breathing behaviors across speech tasks and by respiratory health. Additional repeated-measures multivariate analyses and 1-way analyses of variance were conducted on temporal, aerodynamic, and linguistic measures. RESULTS: There was a significant main effect of task and a significant interaction effect of COPD and task on chest wall movements. Rib cage movements varied by task, whereas abdominal movements were as predicted. There was a significant difference in utterance length by task. There were no main effects of COPD on the chest wall and no significant group differences in utterance length, aerodynamic measures, or intelligibility. The TE speakers were generally accurate in inspiring at appropriate linguistic boundaries. CONCLUSIONS: The results suggest that there is robust control for speech breathing following laryngectomy, but that there is also increased effort within the chest wall. Implications for future research considerations are discussed. PMID- 22312926 TI - Retrograde sialendoscopy: a new technique for avoiding retained ductal stones. AB - OBJECTIVES: Recurrent infection from stones retained in Wharton's duct after submandibular gland resection warrants intraoperative attention to the duct remnant. Our hypothesis was that retrograde sialendoscopy would help ensure complete stone removal in submandibular gland removal for sialolithiasis. METHODS: We reviewed 9 sequential cases of submandibular sialolithiasis treated surgically via open procedures at a tertiary care center by a single surgeon between November 2007 and December 2009. The review focused on the clinical history and intraoperative findings. RESULTS: We identified successful application of a new technique of retrograde sialendoscopy performed to detect and remove stones that were retained in Wharton's duct at the time of submandibular gland resection. An index case of complications from a stone retained after submandibular gland resection is presented in a sequential series of cases in which retrograde sialendoscopy was developed. CONCLUSIONS: Retrograde sialendoscopy is a novel technique that is useful as an adjunct to standard submandibular gland resection in the management of sialolithiasis. PMID- 22312927 TI - "Natural" decannulation in patients with Robin sequence and severe airway obstruction. AB - OBJECTIVES: Airway management in infants with Robin sequence (RS) remains controversial, ranging from conservative to operative methods. In some centers, tracheostomy remains the mainstay for those infants with severe respiratory obstruction. The goals of this retrospective case cohort study were to determine the length of time to decannulation without further surgical intervention (ie, "natural" decannulation) in patients with severe RS who underwent tracheostomy and to investigate potential factors associated with successful decannulation. METHODS: We reviewed all infants with RS treated at a large tertiary center from 1994 to 2010. Patients who had undergone tracheostomy were identified. Baseline demographics, complications, deaths, and time to "natural" decannulation were recorded. Statistical analysis was performed with univariate analysis and Kaplan Meier log-rank tests. RESULTS: Of 61 infants with RS with obstructive events, 25 infants (14 with isolated RS and 11 with syndromic RS) required tracheostomy. At a mean follow-up of 4 years, the rate of tracheostomy-specific complications was 52%; the tracheostomy-specific mortality rate was 12%. Overall, 13 of 25 infants (52%) were "naturally" decannulated, with a median time to decannulation of 97 months. Patients with syndromic RS had a significantly longer median time to decannulation than did those with isolated RS (more than 73 months versus 19 months, respectively; p = 0.019). In addition, patients with long-term tracheostomy dependence had significantly higher maximum carbon dioxide levels before tracheostomy than did patients who were successfully decannulated (82.4 versus 63.2 mEq/L, respectively; p = 0.02). CONCLUSIONS: Tracheostomy in infants with RS is associated with inordinately high rates of mortality, morbidity, and long-term tracheostomy dependence, particularly in patients with syndromic RS and in those with high maximum carbon dioxide levels before tracheostomy. PMID- 22312928 TI - Vocal fold stellate cells in the human macula flava and the diffuse stellate cell system. AB - OBJECTIVES: Hepatic stellate cells (HSCs) are desmin-positive cells with perinuclear vitamin A droplets that play important roles in liver fibrogenesis. Morphologically similar cells have been found at many extrahepatic sites. Consequently, the concept of a diffuse stellate cell system has been proposed. Vocal fold stellate cells (VFSCs) in the human maculae flavae (MFs) are starlike in shape and possess lipid droplets and store vitamin A. In this study, the relationship between the VFSCs in the human MFs and the diffuse stellate cell system was investigated. METHODS: Light and electron microscopic investigations and immunohistochemical studies were performed in 5 samples of human adult vocal fold mucosa. RESULTS: The VFSCs showed the morphological features of the HSCs (ie, they were desmin-positive cells with perinuclear vitamin A droplets). Glial fibrillary acidic protein and vimentin were identified in the VFSCs in the MFs. CONCLUSIONS: The VFSCs in the human adult MFs express the neural and muscle associated proteins seen in HSCs. Our present and previous investigations suggest that the VFSCs in the human MFs are a member of the diffuse stellate cell system. The VFSCs are considered a new category of cells in the human vocal fold. The MFs are proposed to be special microenvironments, known as niches, that nurture a pool of VFSCs. PMID- 22312929 TI - Congenital laryngomalacia: symptom duration and need for surgical intervention. AB - OBJECTIVES: We undertook to characterize the natural course and duration of stridor and other symptoms associated with laryngomalacia and determine the need for surgical intervention. METHODS: A retrospective observational study was performed at a tertiary children's hospital of 120 consecutive cases of congenital laryngomalacia diagnosed and treated by the senior author between July 2005 and June 2009. The patients' symptoms, associated symptoms, and required interventions were recorded. RESULTS: In 115 cases that were managed without surgery, stridor resolved at a mean patient age of 7.6 months. Five patients (4.2%) required supraglottoplasty to resolve their airway obstruction. The patients who required surgery presented emergently to the hospital 80% of the time, and at a younger mean age (45 days) than did patients who did not require surgery (95 days; p = 0.13); these findings suggest the severe nature of their symptoms. Presenting symptoms of dyspnea or accessory muscle use, feeding difficulties, apnea, cyanosis, oxygen desaturation, and failure to thrive were significantly associated with the requirement for operative intervention (all p values less than 0.02). Nonoperative management included placement of a nasogastric tube due to aspiration in 3 patients. CONCLUSIONS: The stridor resolved at an average age of 7.6 months of age in patients with laryngomalacia managed without surgery. A young age at presentation and emergent evaluation in the hospital are associated with a higher degree of symptom severity and a higher rate of surgical intervention. Surgical intervention was necessary to treat laryngomalacia in 4.2% of patients in this study population. PMID- 22312930 TI - Yeast colonization of voice prostheses: pilot study investigating effect of a bovine milk product containing anti-Candida albicans immunoglobulin A antibodies on yeast colonization and valve leakage. AB - OBJECTIVES: Our goals were to determine whether a bovine milk product containing anti-Candida albicans immunoglobulin A antibodies ("immune milk") could reduce the adherence of C albicans to voice prosthesis silicone in vitro, and whether administration of the milk could reduce C albicans colonization and voice prosthesis damage in vivo. METHODS: An in vitro assay of C albicans attachment to silicone was developed with radiolabeled C albicans. A pilot crossover in vivo trial, over 3 periods of 3 months, was also undertaken for 4 patients with voice prostheses, comparing daily administrations of immune milk and a control milk product. The prosthesis valves were replaced at each changeover and were assessed for wet weight of removable biofilm, yeast numbers in removable biofilm, valve leakage, and valve damage. RESULTS: Immune milk inhibited C albicans adherence to silicone in vitro. However, in a small clinical pilot study, this effect was not replicated. CONCLUSIONS: There is scope to further investigate the topical use of immune milk for management of voice prosthesis biofilms. PMID- 22312931 TI - Short-term functional and morphological changes in guinea pig cochlea following intratympanic application of Burow's solution. AB - OBJECTIVES: Burow's solution, comprising aluminum sulfate and acetic acid, is an otic drug formulation applied to the tympanic cavity. We characterized the relationship between the auditory brain stem response (ABR) thresholds and the area of the capillary basement membrane anionic sites in the stria vascularis after the application of Burow's solution. METHODS: We used cationic polyethylenimine (PEI) to observe changes in the capillary basement membrane anionic sites in the stria vascularis. Burow's solution was dropped directly onto the round window membrane and retained for 2 hours. The ABRs were recorded at 4, 8, and 20 kHz immediately before surgery and before decapitation. The cochlea was extirpated immediately or 2 days after the surgery and immersed in cationic PEI solution. The PEI distribution associated with the capillary basement membrane anionic sites was measured in the basal and third turns. RESULTS: The ABR threshold shifts at 4, 8, and 20 kHz were significantly increased immediately after the surgery, whereas those at 4 and 8 kHz, but not at 20 kHz, had recovered 2 days after the surgery. Further, the PEI distribution was significantly decreased immediately after the surgery and had recovered 2 days after the surgery. CONCLUSIONS: Although Burow's solution may cause an acetic low pH in the stria vascularis and a temporary ABR threshold shift at 4 and 8 kHz, the permanent ABR threshold shift at 20 kHz cannot be attributed to the acetic low pH. PMID- 22312932 TI - Potential hypersensitivity due to the food or food additive content of medicinal products in Spain. AB - The Drug Allergy Committee of the Spanish Society of Allergology and Clinical Immunology reviewed the allergenic potential of several substances of food origin that are found in the composition of some drugs. Despite recent legislation on labeling, many labels do not clearly state whether the drug contains raw material (active ingredients, excipient, or other manufacturing intermediate) with an origin in any of the substances in the list of the 14 groups of food allergens that are subject to mandatory declaration. The objective of legislation is that the drug package, the Summary of Product Characteristics, and the patient information leaflet clearly state the food content in order to improve the safety of allergic patients. Therefore, any food or allergen derivative that must be declared should be clearly stated on the drug label. Of all the evaluated products, egg and milk derivatives are the most frequently discussed in literature reviews. The natural or synthetic origin of potentially allergenic substances such as lysozyme, casein, lactose, albumin, phosphatide, and aromatic essences should be clearly stated. Providing this information has 2 clear advantages. First, allergic reactions to drugs in patients with food allergy could be avoided (if the substances have a natural origin). Second, prescription would improve by not restricting drugs containing synthetic substances (which do not usually induce allergic reactions). PMID- 22312933 TI - Lack of association between aspirin-triggered 15-hydroxyeicosatetraenoic acid release and mast cell/eosinophil activation in nasal polyps from aspirin sensitive patients. AB - BACKGROUND: The mechanism of aspirin sensitivity in patients with asthma and rhinosinusitis has been attributed to arachidonic acid metabolism abnormalities. OBJECTIVE: We aimed to test whether aspirin-triggered generation of 15 hydroxyeicosatetraenoic acid (15-HETE) in nasal polyp dispersed cells (NPDCs) from aspirin-sensitive patients is associated with activation of inflammatory cells. METHODS: Polyps were obtained from 11 aspirin-sensitive and 19 aspirin tolerant patients with chronic rhinosinusitis. NPDCs were stimulated by aspirin or calcium ionophore. Levels of 15-HETE, leukotriene (LT) C4, eosinophil cationic protein (ECP), and tryptase were measured in NPDC supernatant. RESULTS: NPDCs from aspirin-sensitive patients contained more eosinophils (14% vs 9%, P < .05) and released 2.4-fold more ECP (P < .01) at baseline. Stimulation with aspirin (200 microM) resulted in a significant increase in 15-HETE generation only in tissue from aspirin-sensitive patients (mean increase, 82%) but did not induce any increase in the release of LTC4, ECP, or tryptase. Preincubation with calcium ionophore resulted in significantly enhanced generation of 15-HETE, ECP, tryptase, and LTC4 in patients from both groups. Incubation of NPDCs with misoprostol inhibited aspirin-induced 15-HETE generation in aspirin-sensitive patients and calcium ionophore-induced 15-HETE, ECP, and tryptase release in both aspirin-sensitive and aspirin-tolerant patients. CONCLUSION: Our study demonstrated that aspirin-induced 15-HETE generation in nasal polyps from aspirin sensitive patients is not associated with activation of mast cells and eosinophils. Misoprostol has a potent inhibitory effect on the activation of cells derived from the site of nasal mucosal inflammation, regardless of sensitivity to aspirin. PMID- 22312934 TI - Efficacy of intravenous immunoglobulin treatment in children with common variable immunodeficiency. AB - BACKGROUND: Children with common variable immunodeficiency (CVID) have increased susceptibility to infections. OBJECTIVE: We evaluated the role of intravenous immunoglobulin (IVIG) replacement therapy on the clinical outcome of patients with CVID. METHODS: We studied children diagnosed with CVID and treated with IVIG (500 mg/kg every 3 weeks). RESULTS: The study population comprised 29 children with CVID (mean [SD] age, 11.8 [6.1] years) with at least 1 year of follow-up before IVIG replacement therapy. Mean follow-up duration was 5.6 (3.5) years (range, 15 months-14 years). During therapy, median serum IgG levels increased from 410 to 900 mg/dL. The mean number of respiratory infections per patient per year decreased significantly from 10.2 to 2.5. The annual number and length of hospital stays decreased significantly from 1.36 to 0.21 and 16.35 to 6.33 days per patient, respectively. The mean annual number of antibiotics used decreased significantly from 8.27 to 2.50 per patient. Twelve patients had developed bronchiectasis before initiation of IVIG; 3 patients were cured of this condition. Age at diagnosis, diagnostic delay, number of respiratory tract infections, and number of antibiotics were found to be significantly higher in patients with bronchiectasis, as was lower B-cell percentage. However, gastrointestinal involvement due to noninfectious causes did not improve significantly after IVIG replacement therapy. CONCLUSION: CVID patients treated with IVIG (500 mg/kg every 3 weeks) had satisfactory serum IgG levels, fewer respiratory tract infections, fewer and shorter hospital stays, and reduced antibiotic usage. However, no effect on gastrointestinal involvement was observed. Early IVIG replacement therapy is important in preventing bronchiectasis. PMID- 22312935 TI - Cupressus arizonica pollen: a new pollen involved in the lipid transfer protein syndrome? AB - BACKGROUND: Lipid transfer proteins (LTP) are responsible for systemic manifestations in food allergy. Their relationship with pollinosis is not clear. In our area, many patients allergic to multiple LTP-containing foods present pollinosis due to Cupressus arizonica. METHODS: We selected 6 patients with cypress pollinosis and food allergy to peach. Skin prick tests (SPT) were performed for pollens (grass, cypress, wall pellitory, plane tree, and olive tree) and plant foods (hazelnut, kiwifruit, peach peel, maize, wheat, peanut, lettuce, apple, mustard, and melon). In vitro assays included specific immunoglobulin (Ig) E to C arizonica and peach LTP (Pru p 3), enzyme allergosorbent test (EAST) inhibition, immunoblotting, immunoblotting-inhibition, and immunocytochemical techniques for the detection of Pru p 3-like LTP in cypress pollen grains. RESULTS: SPT were positive for C arizonica, peach, lettuce, mustard, and hazelnut in all patients. Specific IgE to C arizonica and Pru p 3 was positive in all but 1 patient, whose Pru p 3 IgE was negative. Immunoblotting under nonreducing conditions with C arizonica extract and patients' sera showed a band at 14-15 kDa that was inhibited by Pru p 3. Pru p 3 partially inhibited the C arizonica pollen extract in EAST-inhibition. Pru p 3 like LTP was localized in the cytoplasm and walls of C arizonica pollen grains. CONCLUSION: A 15-kDa allergen in C arizonica pollen was found in a group of patients presenting peach allergy and respiratory symptoms to cypress. In vitro tests and immunocytochemical techniques indicate that this protein is an LTP. PMID- 22312936 TI - Basophil activation reveals divergent patient-specific responses to thermally processed peanuts. AB - INTRODUCTION: The impact of processing on the allergenicity of peanut (Arachis hypogaea) proteins has traditionally been studied using immunoglobulin (Ig) E binding assay. However, as this technique does not assess the potential of an allergen to trigger basophils and mast cells, studies based on it can hardly be considered complete. We evaluated the effect of processing on peanut allergenicity using flow-cytometric quantification of in vitro basophil activation (basophil activation test [BAT]). PATIENTS AND METHODS: Basophils from 10 patients with severe peanut allergy and 3 peanut-tolerant individuals were stimulated with extracts from 5 raw and thermally processed peanut varieties. Data were compared using protein staining (sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE]) and IgE immunoblotting. RESULTS: Stimulation with different extracts resulted in patient-dependent and variety-dependent effects on basophil activation. SDS-PAGE revealed a considerable loss of identifiable bands, especially for the South Africa Common Natal, Argentina Runner, and US Virginia varieties. The results of IgE immunoblotting in patients were similar, irrespective of the responses observed in the BAT. CONCLUSIONS: The impact of thermal processing on the capacity of peanuts to trigger basophils seems highly divergent between patients and cannot be predicted using SDS-PAGE or IgE binding. BAT can be considered a complementary tool for the evaluation of food allergenicity. PMID- 22312937 TI - Bronchial hyperresponsiveness and airway inflammation in patients with seasonal allergic rhinitis. AB - BACKGROUND: Allergic rhinitis is a chronic inflammatory disease induced by an immunoglobulin (Ig) E-mediated reaction after exposure to an allergen. Many patients with allergic rhinitis and no clinical evidence of asthma show a heightened response to histamine. OBJECTIVES: The aims of the study were to measure changes in markers of airway inflammation in patients with seasonal allergic rhinitis and estimate changes in bronchial reactivity before and during the pollen season. METHODS: The study sample comprised 22 patients sensitized to grass pollen and 10 healthy volunteers. Based on the results of the bronchial provocation test (BPT) during the pollen season, we divided patients into those with and without bronchial hyperresponsiveness (BHR). We determined changes in nitrite and pH in exhaled breath concentrate (EBC), fraction of exhaled nitric oxide (FE(NO)), blood eosinophil count, and BPT results before and during the pollen season. RESULTS: In allergic rhinitis patients with BHR, we observed an increase in EBC nitrite (5.44 [2.33] vs 8.57 [3.35] nmol/mL, P = .02) and FE(NO) (20.90 [13.68] vs. 43.40 [31.60] ppb, P = .02) and a decrease in EBC pH (7.07 [0.33] vs. 6.74 [0.28], P = .01) during the pollen season. In allergic rhinitis patients with BHR, the increase in BHR was negatively correlated with increased FE(NO) and EBC nitrite and positively correlated with a decrease in EBC pH during the pollen season. CONCLUSIONS: Our results revealed a relationship between increased BHR in patients with seasonal allergic rhinitis and changes in airway inflammation markers. EBC pH, EBC nitrite concentration, and FE(NO) could act as prognostic markers for identifying patients at risk of developing asthma. PMID- 22312938 TI - Asthma diagnosis is not associated with obesity in a population of adults from Madrid. AB - BACKGROUND: Several studies have suggested a relationship between asthma and obesity; however, this relationship is unclear when obesity is compared with bronchial hyperresponsiveness to methacholine. AIM: To determine whether obesity is associated with a diagnosis of asthma. METHODS: We conducted a cross-sectional study in a population of Spanish adults in the north of Madrid, Spain between 2003 and 2007. The patients included had experienced asthma symptoms during the previous year, but had a ratio of forced expiratory volume in the first second of expiration (FEV1) to forced vital capacity (FVC) of > 70%. Diagnosis was confirmed by the presence of symptoms and demonstration of bronchial hyperresponsiveness to methacholine. Obesity was measured by body mass index (BMI). Adjusted odd ratios (OR) were obtained by logistic regression. RESULTS: Of a total of 1424 patients included, 251 (17.6%) were diagnosed with asthma. These patients were younger (P < .001) and had lower BMI (P < .001) and lung function parameters (FEV1 and FEV1/FVC ratio) than individuals without asthma (P < .001). After adjusting the model for age, gender, baseline FEV1, and FEV1/FVC ratio, patients with overweight or obesity were not more frequently diagnosed with asthma than those with normal weight (OR, 0.848 [95% confidence interval (CI), 0.59-1.20]; and OR, 0.616 [95% CI, 0.38-0.99], respectively). In addition, obese males were more frequently diagnosed with asthma than obese females (P < .041). CONCLUSIONS: In this study, obesity and overweight were not associated with a diagnosis of asthma based on the presence of consistent symptoms and demonstration of airway responsiveness to methacholine. PMID- 22312939 TI - Chronic autoimmune urticaria: frequency and association with immunological markers. AB - BACKGROUND: Chronic autoimmune urticaria (CAU), a subgroup of chronic idiopathic urticaria (CIU), is characterized by severe and persistent wheals accompanied by redness and itching. Diagnosis is almost completely based on clinical suspicion and the results of the autologous serum skin test (ASST). OBJECTIVES: To determine the frequency of CAU and compare the clinical and laboratory parameters of patients with positive and negative ASST results. PATIENTS AND METHODS: A total of 165 patients with chronic urticaria (CU) were enrolled; 31 were excluded (known causes and pregnancy/ breastfeeding), leaving 134 patients with CIU. A clinical evaluation and routine and specific laboratory tests were performed. RESULTS: The cause of CU was identified in 18.9% of patients; 81.2% patients were considered to have CIU. The ASST result was positive in 39.6% of patients with CIU, who had more frequent urticaria attacks than patients with a negative ASST result. Patients with positive results had a higher urticaria activity score than those with negative results, although the difference was not statistically significant. As for immunological markers, the absolute eosinophil count and serum immunoglobulin (Ig) E titer were lower in patients with a positive ASST result than in those with a negative ASST result, although, again, the difference was not statistically significant (P = .07). Antithyroid antibody titer and B cell percentage were higher in patients with a positive ASST result than in those with a negative result, and the difference was statistically significant (P = .04 and .004, respectively). CONCLUSIONS: ASST remains a baseline diagnostic test for CAU. Patients with CAU had more frequent attacks and higher antithyroid antibody titers and peripheral B-cell percentages, as well as lower absolute eosinophil counts and serum IgE concentrations. PMID- 22312940 TI - Interleukin 17A and F and asthma in Saudi Arabia: gene polymorphisms and protein levels. AB - BACKGROUND: Asthma is a multifactorial disorder, and both genetic and environmental factors contribute to its development. We investigated the possible association between asthma and 5 single-nucleotide polymorphisms (SNPs) in the interleukin 17 (IL17) gene--rs17880588 (G/A) and rs17878530 (C/T) in IL17A and rs763780 (T/C), rs11465553 (T/C), and rs2397084 (G/A) in IL17F--and compared levels of the proteins IL17A and IL17F in asthma patients with those of controls. PATIENTS AND METHODS: The study group included 100 asthma patients and 102 ethnically matched controls. Genotyping was performed on purified DNA using reverse transcriptase-polymerase chain reaction with specific primers and probes. Levels of IL17A and IL17F were measured in plasma using enzyme-linked immunosorbent assay. RESULTS: Genotyping showed that AG heterozygotes of rs17880588 in IL17A were significantly more common in the control group than among the asthma patients (P < .05); no significant associations were observed for any of the other SNPs examined. Levels of IL17A and IL17F were both higher in asthma patients (IL17A, 2.242 [0.099] vs 2.752 [0.287] pg/mL; IL17F, 236.01 [38.28] vs 700 [201.078] pg/mL). The difference was statistically significant for IL17F (P = .025, t test). Levels of IL17A and IL17F were positively and significantly correlated in the asthma patients CONCLUSION: Of all the SNPs analyzed, only rs17880588 showed a significant association with asthma in the Saudi population we studied. Levels of IL17A and IL17F were significantly upregulated in the asthma patients. The morphology of IL17F appeared to affect expression levels. PMID- 22312941 TI - Prevalence, severity, and time trends of allergic conditions in 6-to-7-year-old schoolchildren in Taipei. AB - BACKGROUND: Atopic diseases, including asthma, allergic rhinitis, and atopic eczema, are major illnesses among children. Recent studies conducted worldwide have shown diverse trends in the prevalence of asthma, with a steady increase detected in industrialized countries. Other studies, however, have revealed a leveling trend or even a declining prevalence. OBJECTIVE: The purpose of this study was to evaluate the current prevalence of allergic conditions in 6-to7-year old schoolchildren in Taipei, Taiwan, and to analyze time trends. METHODS: We evaluated the prevalence and severity of asthma and other allergic conditions using a phase I International Study of Asthma and Allergies in Childhood core written questionnaire previously administered in Taipei in 1994 and 2002. RESULTS: A total of 24 999 first-grade students from 153 elementary schools completed the questionnaire. The proportion of children with wheeze ever and nocturnal cough in the past 12 months was significantly increased in 2007 compared to 1994 and 2002. No significant differences were detected in the prevalence of current wheeze or physician-diagnosed asthma. The prevalence of severe wheezing symptoms in the past 12 months (> or = 4 attacks of wheeze, > or = 1 night of sleep disturbance due to wheeze per week, wheeze-limiting speech, and exercise-induced wheeze) decreased significantly. The prevalence and severity of rhinitis symptoms increased significantly during the 13-year period analyzed. The prevalence of eczema symptoms-defined as recurrent itchy rash and typical atopic eczema distribution in the past 12 months--also increased. CONCLUSIONS: We observed an increase only in the prevalence and severity of current allergic symptoms in allergic rhinitis and atopic eczema. PMID- 22312942 TI - Unpredicted adverse reaction to omalizumab. AB - Despite promising reports of the use of omalizumab as add-on therapy in patients with systemic mastocytosis and recurrent anaphylaxis during specific venom immunotherapy (VIT), unpredicted adverse effects may lead to therapy failure. We present the case of a patient with systemic mastocytosis and Hymenoptera venom allergy who was administered omalizumab as add-on therapy to improve VIT tolerability after repeated severe adverse reactions despite H1/H2-antihistamine prophylaxis. We describe an unexpected discontinuation of omalizumab following successful initiation of VIT in a patient with systemic mastocytosis, with subsequent lack of tolerability of VIT. An interesting aspect of this case is the correlation of basophil activation test results with both clinical tolerability and VIT intolerance. PMID- 22312943 TI - Anaphylaxis associated with the ingestion of Goji berries (Lycium barbarum). AB - Goji berry (wolfberry), a member of the Solanacea family, has been recently introduced in Western countries and its consumption has increased rapidly. The objectives of the study were to describe the cases of 2 patients who experienced allergic symptoms after Goji berry consumption, to identify the protein profile of the extract, to analyze the allergenic profile of individuals, and to determine cross-reactivity with other members of the Solanaceae family (tomato). We describe 2 cases of allergic reaction, 1 of which was an anaphylactic reaction, after Goji berry ingestion. A Goji berry extract was manufactured and immunochemically characterized. The patients were skin prick tested with a battery of common aeroallergens including mites, epithelia, and molds. Individuals were also skin prick tested with food allergens, including Goji berries. A positive skin prick test and specific immunoglobulin (Ig) E to Goji berry was detected in both cases. Serum samples recognized a 9-kDa band, probably related to lipid transfer proteins (LTPs). Cross-reactivity with tomato was analyzed by inhibition studies, which showed that the 9-kDa band was totally inhibited by the tomato extract. This study describes the first 2 cases of allergic reaction following Goji berry ingestion. LTPs seem to be involved in allergic sensitization to Goji berries, as evidenced by cross-reactivity with tomato. PMID- 22312944 TI - Successful desensitization to idursulfase in a patient with type II mucopolysaccharidosis (Hunter syndrome). PMID- 22312945 TI - Molecular characterization of Bruton's tyrosine kinase deficiency in 12 Iranian patients with presumed X-linked agammaglobulinemia. PMID- 22312946 TI - Usefulness of lymphocyte activation test in atorvastatin hypersensitivity. PMID- 22312947 TI - Anaphylaxis caused by Crematogaster cutellaris sting in an Italian child. PMID- 22312948 TI - [The real value of diagnostic methods in case of long time of cessation of occupational exposure to diisocyanates among patients diagnosed in the nofer institute of occupational medicine in Lodz]. AB - BACKGROUND: The aim of the study was to analyze the data obtained during the diagnostic process and their real values in the final diagnosis of patients exposed to diisocyanates amd suspected of occupational allergic disease of the respiratory system The patients have been hospitalized in the Nofer Institute of Occupational Medicine over recent 11 years. MATERIAL AND METHODS: In 1999-2009 we hospitalized 37 patients exposed to diisocyanates and suspected of occupational asthma. RESULTS: Test results of 37 patients were analyzed. The patients were divided into three groups of those with diagnosed occupational asthma, with diagnosed non-occupational asthma and those without any allergic airway disease. 40.0% of patients with occupational asthma, 64.3% of patients with non occupational asthma and 15.4% of patients without any allergic disease were sensitized to at least one of common allergens. We did not find any specific IgE to diisocyanates. Specific challenge tests were performed in all the 37 subjects. We observed positive results of SIT with diisocyanates in 10 patients. CONCLUSIONS: Only specific challenge test with diisocyanates showed the real diagnostic value in case of a 7.5-year cessation of exposure. Determination of serum specific IgE to diisocyanates does not seem to be of clinical value in the diagnosis of diisocyanate-induced asthma in case of a 7.5 year cessation of exposure. Atopy is not the risk factor in diisocyanate-induced asthma. PMID- 22312949 TI - [Occupational exposureto X and gamma rays in Poland in 2010]. AB - BACKGROUND: The paper presents the results of the measurements of ionizing radiation doses received by people occupationally exposed to X and y rays in Poland 2010 provided by the Nofer Institute of Occupational Medicine in Lodz. MATERIALS AND METHODS: The personal dose equivalent Hp(10) measurements were performed using the film method while the Hp(0.07) measurements using ring dosimeters with TL detectors according to the accreditation procedures (No. AB327). The measurements were carried out over two-month periods for Hp(10) and over one- or two-month periods for Hp(0.07). RESULTS: In 2010 the Nofer Institute of Occupational Medicine in Lodz covered more than 27,000 workers with individual whole body dosimetry Hp(10) in 3808 laboratories and 1800 workers with hands dosimetry Hp(0.07) in 152 laboratories. Mean annual dose Hp(10) was 0.5 mSv (annual limit for Hp(10) equals 20 mSv), whereas for Hp(0.07) was 5.6 mSv (annual limit for Hp(0.07) equals 500 mSv). CONCLUSIONS: In 2010, doses higher than the annual limit for both Hp(10) and Hp(0.07) were not recorded. The collected data confirm that the radiation protection of people occupationally exposed to X and gamma rays is satisfactory in Poland. PMID- 22312950 TI - [Assessment of energy and macronutrients supply in daily food rations of people exposed to hand transmitted vibrations]. AB - BACKGROUND: Occupational exposure of workers to mechanical hand transmitted vibrations may result in the development of nonspecific lesions. Balanced diet is one of factors that protect human organism against abnormalities resulting from occupational exposure. The aim of this study was to assess the supply of energy and macronutrients in daily food rations (DFR) of people exposed to hand transmitted vibration. MATERIALS AND METHODS: Eighty workers, including 37 men (mean age 44.6 years) and 43 women (mean age 44 years) exposed to hand transmitted vibrations were recruited in this study. Of those, 72 people worked in crystal glassworks as glass cutters, 5 people were physiotherapists and 3 were woodcutters. For all workers, there was measured exposure to hand transmitted vibration. Nutritional status was assessed using 24-hour dietary recall; the procedure was repeated 3 times. The results of the nutritional assessment were compared with recommended daily allowances (RDA) for energy, protein, minerals and vitamins, total carbohydrates, total fat, saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), cholesterol and dietary fibre. RESULTS: The average intake of energy in daily food rations of the women was too low while men received the appropriate amount of energy. Average protein intake by men and women was higher than the relevant RDA. The average amount of carbohydrates received by the surveyed women and men were too low, just as the consumption of PUFA, dietary fibre, potassium and calcium. We also found an excessive, average supply of total fat, MUFA, SFA, cholesterol and most of the vitamins with the DFR of the women and men. CONCLUSIONS: The nutrition in the group of workers exposed to hand transmitted vibration was found to be imbalanced due to excessive intakes of total fat, saturated fatty acids and cholesterol combined with insufficient consumption of carbohydrates, dietary fibres, potassium and calcium. The co-occurrence of vibration and imbalanced diet may increase the susceptibility of the subjects to cardiovascular and bone diseases. PMID- 22312951 TI - [Conscious family planning among women living the Lodz area, including their education and nature of work]. AB - BACKGROUND: The aim of this research was to analyze and critically evaluate knowledge of conscious preparation for motherhood and proper control of the course of pregnancy among women, aged 17-35, representatives of social and occupational groups in the region of Lodz. MATERIAL AND METHODS: The research tool was a questionnaire survey, conducted in a grpup of 455 women, living in the Lodz, agglomeration and representing schoolgirls and students, female white collar and blue-collar workers, including: teachers and office workers. The developed questionnaire included questions concerning: knowledge about risks for pregnancy and knowledge of pregnancy preparation. To assess the level of knowledge about the preparation for planned pregnancy the quantitative indicator was used. The value of the indicator expressed the number of points obtained by respondents for their knowledge of specific harmful factors and diagnostic tests, which play an important role during pregnancy. RESULTS: Knowledge of more than 50% of respondents was rated "less than good". The level of knowledge about preparation for pregnancy differed significantly in particular age, education and occupational groups. It was observed that about 57% of respondents did not have sufficient knowledge about the need to control blood glucose level before and during pregnancy, 33% did not know about harmfulness of passive smoking, and 34% about the need of using folic acid. CONCLUSIONS: Knowledge of the proper preparation for pregnancy among professionally active women needs to be significantly enhanced. Knowledge among teachers who should be an important source of essential information is not satisfactory and should also be better developed. Intervention programs concerning the preparation for pregnancy should be differentiated according to age, education and occupational status of recipients. PMID- 22312952 TI - [Relation between occupation and health related quality of life of pregnant women]. AB - BACKGROUND: The aim of this study was to find out the relationship between occupation and health-related quality of life. MATERIAL AND METHODS: The study included 504 pregnant women. Two questionnaires, SF-36v2 and EQ-5D, were used to estimate health-related quality of life. The information on socio-economic status were gathered by performing the third survey. RESULTS: The study evidenced that the health-related quality of life of working women was significantly better than that of those who were on sick leave or unemployed. In the study group, white collar workers had significantly more childbirths in the past than blue collar workers (p = 0.0055). The mean age ofprimiparas employed as white collar workers was 28 while the mean age of blue-collar primiparas was 26, and the difference was significant (p = 0.0000). CONCLUSIONS: The occupation is important not only because it decides about the economic status, but it also influences the health related quality of life of pregnant women. PMID- 22312953 TI - [The evaluation of the Kujawsko-Pomorski program of mental health promotion at work based on the institutions' self-assessment questionnaire: results of and experience gained from the first stage of implementation]. AB - BACKGROUND: The program has been organized at two levels: (1) institution and (2) voivodeship. Institutions have prepared programs adapted to their needs. Their actions were supported by voivod coordinators. The implementation of the first stage ofthe program has been evaluated. The evaluation was based on the data gathered by using the institutions' self-assessment questionnaire. The aim of the study was to present main results obtained by the institutions participating in the program. Based on these the implementation strategies at the voivodeship level were analyzed. MATERIAL AND METHODS: The questionnaire helps to identify stress risk factors, as well as to initiate intervention plans, assess determinants of their implementation, and also to evaluate the status quo of already completed ventures aimed at reducing stress. It helped to gather the information from all 30 institutions, which have participated in the program. RESULTS: Before joining the program only 50% of institutions had considered stress at work in their evaluation of occupational risks. Only two third of them have been involved in any activities aimed at reducing stress, and only half of them have consulted them with employees. Twice as many institutions assessed the opportunities for reducing stress problems as small. CONCLUSIONS: It is needed to improve the reliability of data and increase the utilization of the evaluation results by the institutions. The program strategy at the voivod level should be modified, employers' attitudes toward the problem of reducing stress at work properly shaped and the competence and involvement of leaders increased. PMID- 22312954 TI - [Organizational climate and burnout syndrome]. AB - BACKGROUND: The paper addresses the issue of organizational climate and burnout syndrome. It has been assumed that burnout syndrome is dependent on work climate (organizational climate), therefore, two concepts were analyzed: by D. Kolb (organizational climate) and by Ch. Maslach (burnout syndrome). MATERIALS AND METHODS: The research involved 239 persons (122 woman, 117 men), aged 21-66. In the study Maslach Burnout Inventory (MBI) and Inventory of Organizational Climate were used. RESULTS: The results of statistical methods (correlation analysis, one variable analysis of variance and regression analysis) evidenced a strong relationship between organizational climate and burnout dimension. As depicted by the results, there are important differences in the level of burnout between the study participants who work in different types of organizational climate. CONCLUSIONS: The results of the statistical analyses indicate that the organizational climate determines burnout syndrome. Therefore, creating supportive conditions at the workplace might reduce the risk of burnout. PMID- 22312955 TI - [Occupational allergy in transport workers--underestimated hazard]. AB - Transport workers, subjected to variable direct exposure to allergens in the workplace, are an occupational group at risk of developing occupational allergic diseases of the respiratory system as well as the skin. Their work environment is characterized by considerable diversity of both chemical and biological sensitizers. Sensitization occurs due to occupational exposure to allergens mainly by inhalation or direct skin contact. Therefore, it is necessary to be aware of the presence of strong allergens in the work environment to introduce appropriate preventive measures and to reduce the adverse health effects resulting from the exposure. This publication presents the most important allergens described as causal factors of occupational allergy among transport workers and the basic principles of diagnostics and medical certification of these diseases. PMID- 22312956 TI - [The effect of dioxins on the human organism--epidemiological studies]. AB - For many years dioxins have been the subject of the interest to many research centers due to their widespread occurrence, and high toxicity, and thus they are supposed to be significantly dangerous to humans. In general, dioxins affect all human beings. Workers employed in different branches of industry (chemical, metallurgical and pulp sectors) are especially at high risk. Based on recent epidemiological studies, this article aims the mechanism by which dioxins exert their effect on tumors induction, formation of insulin-resistance, fertility in men and women as well as children development. Research studies, presented in this article, have not confirmed that dioxins existing in uncontaminated environments can pose serious danger to human health. PMID- 22312957 TI - [The role of psychosocial work factors in the development of musculoskeletal disorders in workers]. AB - The aim of the study was to determine the role of psychosocial work factors in the development of musculoskeletal disorders in workers. It should be stressed that over a decade these disorders have been the subject of studies because of complaints reported not only by workers performing heavy physical work or working in awkward, forced body posture. It has also been acknowledged that stress at work caused by various psychosocial work factors can significantly influence their development. One of the models, most popular nowadays, was used in the study. It takes into account various risk factors in the etiology of cervical spine disorders. Based on this model it was shown that certain psychosocial and cultural variables (e.g., work demands and control, individual variables, individual values, work group's culture) may constitute occupational stressors and, when combined with physical load factors, may lead to stress and musculoskeletal disorders. It was also indicated that such psychosocial work factors as excessive work demands (quantitative or qualitative), inadequate control at work or lack of social support are the most frequent sources of work related stress. The article presents the results of some prospective studies in which the role of these factors in the development of musculoskeletal disorders has been considered. Apart from work properties (factors), the role of other psychological variables was shown; these include: work involvement, perfectionism, negative affectivity or work style, which in numerous studies turned out to be important risk factors in the development of musculoskeletal disorders. Finally, potential mechanisms underlying the relationships between psychosocial factors and musculoskeletal disorders were indicated. However, it was stressed that the majority of them still require to be confirmed in future descriptive or experimental studies. PMID- 22312958 TI - [Occupational factors influencing lung cancer in women in epidemiological studies]. AB - Lung cancer is the most common cancer in men, although the alarming statistics of recent years indicate that this pathology affects also more likely a group of women and in recent years has become the leading cause of cancer deaths among Polish women. This article presents the main issues relating to occupational determinants of lung cancer in women. The results of the analysis show that the number of neoplastic diseases, including the lung cancer, recognized as an occupational disease in Poland is low, particularly among women. A major factor hampering the certification of occupational etiology of lung cancer is a long latency period, no differences in terms of the clinical and morphological characteristics from lung cancer occurring in the general population, and relatively small number of identified occupational carcinogens. Analysis of the available literature on the adverse workplace conditions shows that only a few epidemiological studies focus on the problem of job-related risk among women, and only some of them provide detailed results for lung cancer. Moreover, the abundant literature on the subject concerning the male workers might not be fully relevant because of possible differences in hormonal, genetic and other gender related biological differences that may significantly modify the risk of cancer in women. These aspects cause that the true contribution of occupational factors to the risk of lung cancer, particularly in women, is underestimated. PMID- 22312959 TI - [Quality of life of occupationally active people, aged 45-60, living in the Polish industrial region (Silesian agglomeration)]. AB - BACKGROUND: Among the most important determinants of quality of life are socio economic factors, including economic activity and support of family, environmental and indoor related factors, infrastructure and air quality. The aim of this publication is to identify the factors that determine the quality of life of economically active adults in the industrial agglomeration of Poland. MATERIALS AND METHODS: The epidemiological cross-sectional study was carried out among the economically active population of the Silesian Agglomeration. A short version of the WHOQOL-BREF questionnaire was used to ascertain the quality of life of individuals. Furthermore, the software Statistica 9.0 was used to provide analytical and descriptive statistical data. The influence of age, gender, education, type of activity and living environment were used to assess the quality of life in the somatic, psychological, social and environmental domains. RESULTS: It was found that among the important determinants of quality of life in economically active population, aged 45-60 years, living in the industrial agglomeration, were primarily marital status, education level and the current state of health. The data evidenced the worst quality of life among unmarried persons, persons with lower education levels and persons diagnosed with cardio- or respiratory diseases. CONCLUSIONS: There is a need to develop health conducive behavior among workers by providing training cycles with the involvement of staff supervising occupational health and safety. These types of actions can contribute to improving the quality of life of the working population. PMID- 22312960 TI - [Implementation of the Amiantus project involving prophylactic medical examinations of the former employees of asbestos processing plants]. AB - BACKGROUND: Based on a 11-year implementation of the Amiantus Project, this paper reports the results of prophylactic medical examinations of the former workers of asbestos processing plants. The Project involving employees of 28 former asbestos plants was started by the Ministry of Health in 2000 under the Act on the ban of all products containing asbestos. MATERIAL AND METHODS: Preventive examinations, continued in 13 centers of occupational medicine throughout the whole territory of Poland, have been coordinated by the Nofer Institute of Occupational Medicine in Lodz (NIOM). During the examinations, a specific Examination Form is filled-in by a physician. The Form is then sent to NIOM for monitoring health effects in the population covered by the Project. The results obtained by analyzing the lung radiological images are recorded in the Examination Form according to the ILO 1980 classification of pneumoconiosis. The diagnosis of the asbestos-related pathologies is based on the Helsinki criteria. RESULTS: During the years 2000 2010, altogether 6,853 people were involved in the Project, and they were subjected to a total of 18,955 preventive examinations. Asbestosis was diagnosed in 1475 people, representing 21% of all respondents, lung cancer in 68 and mesothelioma in 40 people. Pleural radiographic changes were observed in 3027 (44%) patients, pulmonary parenchymal opacities in 4086 (60%) patients. The analysis showed that the asbestos-related pathologies were most frequent in the group of former employees of asbestos-cement plants. This group was also characterized by an age-, tenure-, and latency-related increasing trend in the prevalence of silicosis and the frequency of radiographic lesions in the lungs of those subjects. CONCLUSIONS: The continuation of the examinations of former workers of asbestos processing industry has improved the detection of pathologies associated with exposure to asbestos and enabled undertaking an appropriate preventive action. The growing percentage of poorer radiography results reflects the progressive development of pathological processes in the respiratory system of people occupationally exposed to asbestos dust in the past. PMID- 22312961 TI - [Percutaneous exposures in medical personnel]. AB - INTRODUCTION: Medical personnel having daily contacts with patients and, consequently, with their blood and other body fluids constitute a group of an increased risk of percutaneous exposure. The aim of the study was to determine the frequency of medical personnel's contacts with blood and other body fluids as well as to analyze the attitudes of patients infected with blood-borne pathogens and procedures after an occupational exposure to infectious material. MATERIAL AND METHODS: A questionnaire survey of 151 persons. RESULTS: The survey revealed that 77.5% of physicians and 98.2% of nurses experience contacts with infectious material at least several times a week. Simultaneously, 45% of physicians and only 18.9% of nurses stated that they had never been injured with a contaminated needle or other medical instruments. Disconcerting is also the fact that only 45.5% of physicians and 66.7% of nurses report such incidents to their superiors. CONCLUSIONS: The study proved that medical personnel form an occupational group regularly exposed to contacts with patients' blood, body fluids, secretions and excretions. Despite such frequent contacts with patients' body fluids and frequent injuries with medical instruments, their knowledge of blood-borne infections is inadequate. The awareness of giving care to an infected patient makes the majority of medical personnel modify their behavior. PMID- 22312962 TI - [Occupational health protection in business economics--business plan for health intervention]. AB - INTRODUCTION: One of the company's actions for strengthening human capital is the protection of health and safety of its employees. Its implementation needs financial resources, therefore, employers expect tangible effectiveness in terms of health and economics. Business plan as an element of company planning can be a helpful tool for new health interventions management. The aim of this work was to elaborate a business plan framework for occupational health interventions at the company level, combining occupational health practices with company management and economics. MATERIALS AND METHODS: The business plan of occupational health interventions was based on the literature review, the author's own research projects and meta-analysis of research reports on economic relations between occupational health status and company productivity. RESULTS: The study resulted in the development of the business plan for occupational health interventions at the company level. It consists of summary and several sections that address such issues as the key elements of the intervention discussed against a background of the company economics and management, occupational health and safety status of the staff, employees' health care organization, organizational plan of providing the employees with health protection, marketing plan, including specificity of health interventions in the company marketing plan and financial plan, reflecting the economic effects of health care interventions on the overall financial management of the company. CONCLUSIONS: Business plan defines occupational health and safety interventions as a part of the company activities as a whole. Planning health care interventions without relating them to the statutory goals of the company may have the adverse impact on the financial balance and profitability of the company. Therefore, business plan by providing the opportunity of comparing different options of occupational health interventions to be implemented by employers is a key element of the management of employees' health. PMID- 22312963 TI - [Selenium determination in plasma/serum by inductively coupled plasma mass spectrometry (ICP-MS): comparison with graphite furnace atomic absorption spectrometry (GF-AAS)]. AB - BACKGROUND: The present study was aimed at comparing two techniques of selenium (Se) determination in serum/plasma samples: inductively coupled plasma mass spectrometry (ICP-MS) and graphite furnace atomic absorption (GF-AAS). MATERIALS AND METHODS: Blood samples were collected by venipuncture, using Venosafe closed blood sampling system. The samples were centrifuged. The measurements were performed by Elan DRC-e mass spectrometry, Perkin Elmer, SCIEX, USA and Unicam Solar 989 QZ atomic absorption spectrometry. Reference material, Clincheck Serum Control Level 1 (Recipe, Germany), was used to verify the determinations. The Laboratory participates in external quality control (G-EQUAS). RESULTS: Analytical parameters for both techniques are respectively: ICP-MS--precision 5.9%, limit of detection 0.19 microg/l, repeatability 5.5%, trueness 2.4%, bias 97.6%, GF-AAS--precision 8%, limit of detection 3.4 microg/l, repeatability 7.2%, trueness 6.8%, bias 93.2%. CONCLUSIONS: The benefits of the ICP-MS technique are high accuracy, low detection limits and the possibility of multi-element analysis. PMID- 22312964 TI - [Optimization of methods for measurement and assessment of occupational exposure to electromagnetic fields in physiotherapy (SW diathermy)]. AB - BACKGROUND: Physiotherapists commonly use high-frequency (HF) electromagnetic field (EMF) units for therapeutic heating, whereas they are a source of strong EM fields. High EMF intensity values in places, where physiotherapists perform their occupational duties, require frequent measurements and their exposure must be monitored. Such procedures are obligatory and expensive, but they do not improve working conditions of physiotherapists. The aim of the study was to update the knowledge of actual exposure of physiotherapists to EMF and optimize methodical and decisive procedures. MATERIAL AND METHODS: EMF strength was measured in close proximity of twenty diathermy (SW) units, and in places usually occupied by physiotherapists. Modern digital-readout equipment was used for the measurements. It allowed us to identify the resultant EMF spectrum and to manage the measurement results. Values of the induced current, I(L), in the limbs of 16 physiotherapists were measured. RESULTS: The highest values of EMF strengths were measured for the whole body of the physiotherapist at the console, to 200 V/m and 0.20 A/m, and at the electrodes, to 180 V/m and 0.40 A/m. During intervention procedures, the physiotherapist's hands were exposed to 900 V/m and 2.0 A/m EMF. The maximum value of the exposure W indicator for routine operations was as high as 0.32, and for intervention procedures as high as 1.67. The maximum intensities of induced currents measured in the physioterapist's upper limbs during intervention procedures were up to 120 mA, depending on individual person. CONCLUSIONS: The results have confirmed the high EMF strength values occurring in the real conditions of the work environment of physiotherapists performing routine procedures. High intensity values of currents induced in the limbs of the physiotherapist performing intervention procedures represent a real threat in 25% of cases. The existing obligatory annual monitoring procedures are expensive and completely fail to offer any protection against EMF. The authors of this paper propose to implement a two-stage (obligatory and facultative) monitoring and measurement system. PMID- 22312965 TI - [Etiology, determinants, diagnostics and prophylaxis of occupational allergic respiratory diseases in hairdressers]. AB - Hairdressers are occupationally exposed to many substances both, allergizing and irritating. The continuous development of hairdressing services brings about new risks. The most important allergens are: persulfates (ammonium and potassium), paraphenylenediamine, and latex. A growing number of occupational allergens in the work environment of hairdresses, providing that most of them are low weight allergens, may cause some diagnostic problems. Health risks related with haidressing occupation, have prompted the researchers to pay more attention to risk factors of occupational allergy. Owing to the fact, that first morbid symptoms may occur very early, even during the apprenticeship in a hairdressing school, it is very important to indentify health risks, which can be useful in predicting the onset of occupational allergy and in developing effective prevention methods. The most common allergens at the hairdressers' workplace, risk factors, diagnostics of occupational asthma and rhinitis, as well as the prevention of these diseases are reviewed in this publication. PMID- 22312966 TI - [Recommended general principles of good practice relating to psychological examinations in occupational medicine service]. AB - This paper presents general principles of good practice in prophylactic psychological examinations. The principles are based on the binding law and standards of psychological examinations recommended by the Polish Psychological Association. They also take account of a specific nature of such examinations, resulting from their goals and the subject of their concern. Formal guidelines and health indications concerning this kind examinations, their scope, diagnostic methods, tools and documentation are discussed as well. PMID- 22312967 TI - [New medical standards for evaluation of driving predispositions of people suffering from diabetes mellitus]. AB - As a result of the changed Ordinance of January 7, 2004, issued by the Ministry of Health, new medical standards for assessing people suffering from diabetes mellitus, in terms of their health contraindications for driving, came into force on June 29, 2011. Thus the medical standards for diabetes and driving have been harmonized with EU regulations. New standards for diabetes and driving define the key terms such as severe and recurrent hypoglycemia, and hypoglycemia awareness. In addition, health contraindications for Group 1 and Group 2 driving license, deadline for subsequent medical check-ups and indications for diabetologic consultation are defined. The regulations also introduce a new tool in the form ofa consultation file produced by the diabetologist. The structure of the consultation file imposes on the diabetologist an obligation to provide the physician, certifying the ability or disability to drive, the key diabetologic information. This guarantees an objective medical opinion based on an individual approach appropriate for each case. PMID- 22312968 TI - [The effect of organophosphate pesticides on pancreas]. AB - On the basis of the literature data, the effect of organophosphate pesticides on pancreas, in acute and chronic intoxication, is discussed. The reported studies apply to experimental procedures, as well as to observations of people working in contact with these insecticides. The special attention has been paid to glucose homeostasis and risk of diabetes. PMID- 22312969 TI - [Effects of marijuana and amphetamine (and its derivatives on driving performance based on the driving simulator studies]. AB - This article presents the results of the driving simulator studies of the effects of marijuana and amphetamines on driving performance. The majority of these studies have been focused on identifying the impact of the tested substances on cognitive and psychomotor functions. Most of the findings on marijuana reveal its modest effect on driving ability that increases with the increasing frequency of its use and when used in conjuction with other drugs and alcohol. Similarly, small doses of amphetamines can cause a positive stimulating effect, improving certain cognitive functions, such as vigilance, but it decreases when they are overused and combined with alcohol. The results of the research on drivers' behavior under the influence of amphetamines also indicate deficits in their cognitive functions and tendency to recklessness on the road. The authors also discuss strong and weak points of simulation studies of the effects of psychoactive substances on the driving ability. An attempt was also made to clarify certain ambiguities, which occur in this field of research. A central role of the ethical and methodological limitations of simulation studies were discussed as well. PMID- 22312970 TI - papA gene of avian pathogenic Escherichia coli. AB - P fimbrial adhesins may be associated with the virulence of avian pathogenic Escherichia coli (APEC). However, most APECs are unable to express P fimbriae even when they are grown under conditions that favor P fimbrial expression. This failure can be explained by the complete absence of the pap operon or the presence of an incomplete pap operon in Pap-negative APEC strains. In the present study, we analyzed the pap operon, specifically the papA gene that encodes the major fimbrial shaft, to better understand the pap gene cluster at the genetic level. First, by PCR, we examined a collection of 500 APEC strains for the presence of 11 genes comprising the pap operon. Except for papA, all the other genes of the operon were present in 38% to 41.2% of APEC, whereas the papA was present only in 10.4% of the APEC tested. Using multiplex PCR to probe for allelic variants of papA, we sought to determine if the low prevalence of papA among APEC was related to genetic heterogeneity of the gene itself. It was determined that the papA of APEC always belongs to the F11 allelic variant. Finally, we sequenced the 'papA region' from two papA-negative strains, both of which contain all the other genes of the pap operon. Interestingly, both strains had an 11,104-bp contig interruptingpapA at the 281-bp position. This contig harbored a streptomycin resistance gene and a classic Tn10 transposon containing the genes that confer tetracycline resistance. However, we noted that the papA gene of every papA-negative APEC strain was not interrupted by an 11,104-bp contig. It is likely that transposons bearing antibiotic resistance genes have inserted within pap gene cluster of some APEC strains, and such genetic events may have been selected for by antibiotic use. PMID- 22312971 TI - Impact of fresh or used litter on the posthatch immune system of commercial broilers. AB - This study was carried out to investigate the effects of exposure of growing broiler chickens of commercial origin to used poultry litter on intestinal and systemic immune responses. The litter types evaluated were fresh wood shavings or used litter obtained from commercial poultry farms with or without a history of gangrenous dermatitis (GD). Immune parameters measured were serum nitric oxide (NO) levels, serum antibody titers against Eimeria or Clostridium perfringens, mitogen-induced spleen cell proliferation, and intestinal intraepithelial lymphocyte or splenic lymphocyte subpopulations. At 43 days posthatch, birds raised on used litter from a GD farm had higher serum NO levels and greater Eimeria or C. perfringens antibody levels compared with chickens raised on fresh litter or used, non-GD litter. Birds raised on non-GD and GD used litter had greater spleen cell mitogenic responses compared with chickens raised on fresh litter. Finally, spleen and intestinal lymphocyte subpopulations were increased or decreased depending on the litter type and the surface marker analyzed. Although it is likely that the presence of Eimeria oocysts and endemic viruses varies qualitatively and quantitatively between flocks and, by extension, varies between different used litter types, we believe that these data provide evidence that exposure of growing chicks to used poultry litter stimulates humoral and cell-mediated immune responses, presumably due to contact with contaminating enteric pathogens. PMID- 22312972 TI - A multiplex PCR for detection of poxvirus and papillomavirus in cutaneous warts from live birds and museum skins. AB - Viral cutaneous lesions are frequent in some bird populations, though we are generally ignorant of the causal agent. In some instances, they represent a threat to livestock and wildlife health. We present here a multiplex PCR which detects and distinguishes infection by two such agents, avipoxviruses and papillomaviruses, in avian hosts. We assayed biopsies and superficial skin swabs from field and preserved museum skin specimens. Ninety-three percent of samples from symptomatic specimens tested positive for the presence of avipox (n = 23) or papillomavirus (n = 5). Sixteen and five sequences, corresponding to the P4b and L1 genes, were obtained from avipox and papillomavirus, respectively. One museum specimen, of Fringilla coelebs (chaffinch), was apparently infected with both viruses. Although papillomavirus sequences proved identical to previously published sequences, four novel avipox sequences were generated and used to build a neighbor-joining phylogenetic tree. Our tree recovered a similar topology to that of several recent authors; however, we also propose here two new minor avipox clades (B1b and B3). This multiplex PCR technique shows improved sensitivity compared to other avipox and papillomavirus assays, is able to detect a wide range of avipox and papillomavirus types (it amplifies all three avian derived papillomavirus genera described thus far and sequences from both major avipox clades), and was even able to detect ancient viral DNA contained in museum specimens of greater than 75 years antiquity for both viruses. PMID- 22312973 TI - Identification and virulence characterization of fowl adenoviruses in Korea. AB - Since 2007, 55 adenovirus strains have been isolated from commercial chicken flocks in Korea and have been identified and the pathogenicity of these isolates was confirmed in specific-pathogen-free chickens of different age. Based on sequencing analysis of the hexon gene, 55 FAdV isolates were genetically related to the IBH-2A strain of FAdV3 (4 isolates, 99.2% to 100%), the KR5 strain of FAdV4 (22 isolates, 97.9% to 99.2%), the 764 strain of FAdV9 (11 isolates, 99.1% to 99.3%), and the 1047 strain of FAdV11 (18 isolates, > 99%). Experimental infections with four serotypes of FAdV resulted in high mortality of 18-day-old chicken embryos and 1-day-old chicks with marked liver necrosis similar to those observed in the natural outbreaks. Notably, specific hydropericardium was observed in chicks challenged with the K531 strain (serotype 4). However, 3-wk old chickens challenged with FAdVs, regardless of serotype, did not show any clinical signs or mortality except histologic lesions of focal hepatocytic necrosis with mild lymphocytic infiltration. The results indicate that four FAdV serotypes (3, 4, 9, and 11) are the dominant serotypes of FAdVs in the Korea and are pathogenic enough to cause clinical disease in young chicks. The present investigation provides important information on the epidemiology and pathogenesis of FAdVs and highlights the importance of control strategies against FAdV infection in Korea. PMID- 22312974 TI - Glycosylation of the envelope protein of West Nile Virus affects its replication in chicks. AB - Birds are important for the transmission of West Nile virus (WNV) in nature, but the significance of the potential N-linked glycosylation at position 154 in the WNV envelope (E) protein with regard to viral replication in young chickens has not been assessed. In this study, the effect of glycosylation of the WNV E protein on viral pathogenicity in birds was investigated using young domestic chicks. A higher viral load was detected in the blood and the peripheral organs, particularly the hearts, of 2-day-old chicks inoculated with a glycosylated WNV variant compared to those inoculated with the nonglycosylated variant. There was no significant difference in the neutralizing antibody titers and cytokine expression profiles in chickens inoculated with the glycosylated and the nonglycosylated WNV variants. In contrast, no virus w as detected in the blood and the tissues of 3-wk-old chicks, although the host immune response was induced to similar levels as in the 2-day-old chicks. These data indicate the utility of young domestic chicks as an animal model of WNV infection; they also indicate that glycosylation of the E protein of WNV enhances multiplication in the blood and peripheral organs, which is associated with the strong pathogenicity of WNV in birds. PMID- 22312975 TI - Characterization of a ts-1-like Mycoplasma galisepticum isolate from commercial broiler chickens. AB - Several commercial broiler flocks in northeastern Georgia that were the progeny of the same parent flock (Flock 40) were diagnosed as Mycoplasma gallisepticum (MG) positive by serology, culture, and PCR. Flock 40 had been vaccinated with ts 11 live MG vaccine. Several isolates were obtained from the MG-positive broiler flocks, and these isolates were indistinguishable from the ts-11 vaccine strain by the molecular strain differentiation methods used. A pathogenicity study was performed to compare the virulence of one of the isolates, K6216D, to the ts-11 vaccine strain. K6216D elicited a significantly stronger antibody response and significantly increased colonization of the tracheas and air sacs. K6216D also elicited significantly greater air sac and tracheal lesions than the ts-11 vaccine strain at 10 and 21 days postinoculation (P < or = 0.05). This is the first report of a field case of the apparent reversion to virulence and vertical transmission of the ts-11 vaccine. PMID- 22312976 TI - Rapid detection of group I avian adenoviruses by a loop-mediated isothermal amplification. AB - A loop-mediated isothermal amplification (LAMP) assay was optimized for the rapid detection of Group I avian adenoviruses. A set of six primers was designed from the DNA sequences of hexon genes from Group I avian adenovirus. The assay was performed in a water bath for 60 min at 63 C, and the amplification result was visualized by adding a fluorescence dye reagent or by inspecting the white sediment. The results showed that the LAMP assay could detect all 12 serotypes of Group I avian adenovirus and nine Guangxi Group I avian adenovirus isolates. This avian adenovirus Group I-specific LAMP assay could detect 238 copies of avian adenovirus. No cross-reactions were detected using the LAMP assay with avian adenoviruses type II and III or with other avian viruses. The ability of LAMP to detect Group I avian adenovirus isolates was further evaluated with 184 cloacal swab samples from poultry. In total, 72 out of 184 cloacal swab samples from poultry were identified as positive by LAMP, whereas 45 out of 184 were identified as positive by conventional PCR test. The Group I avian adenovirus specific LAMP results were further confirmed by real-time PCR. This specific LAMP method holds promise as a rapid and specific diagnostic assay for detection of samples from birds suspected of adenovirus infection. PMID- 22312977 TI - Horizontal transmission of Salmonella and Campylobacter among caged and cage-free laying hens. AB - In each of five sequential trials, laying hens (56-72 wk of age) were challenged with Salmonella and Campylobacter, and 1 wk postinoculation, the challenged hens (n = 3) were commingled with nonchallenged hens (n = 12) in conventional wire cages, on all-wire slats, or on all-shavings floor housing systems. After 12 days, challenged and nonchallenged hens were euthanatized for sample collection. Ceca were aseptically collected from all hens, and the spleen, liver/gallbladder (LGB), lower (LRT) and upper (URT) reproductive tracts, and ovarian follicles (mature and immature) were collected from only the challenged hens after commingling. Samples were divided equally and cultured separately for Salmonella and Campylobacter. Differences in the horizontal transmission of the challenge Salmonella to nonchallenged hens housed in cages (12%), on slats (15%), and on shavings (14%) were not significantly different (P > 0.05) from the challenged pen-mate hens over the five trials. However, with the inclusion of residual environmental Salmonella, the recovery of Salmonella from nonchallenged hens housed in cages was lowest at 15%, intermediate for hens on slats at 20%, and highest for hens on shavings at 38%. Among challenged hens housed in cages, Salmonella was recovered from only 27% of the cecum and LRT samples. From challenged hens housed on slats, Salmonella was recovered from 38% of the cecum, 12% of the spleen, 19% of the LGB, 44% of the LRT, and 19% of the URT samples. From challenged hens housed on shavings, Salmonella was recovered from 31% of the cecum; 15% of the spleen, LGB, and URT; and 31% of the LRT samples. Horizontal transmission of Campylobacter among nonchallenged pen-mate hens was significantly lower for hens housed in cages at 28% than for hens on shavings at 47%, with hens on slats being intermediate at 36%. For challenged hens housed in cages, Campylobacter was recovered from 27% of the cecum, 13% of the LRT, 7% of the URT, and 17% of the follicle samples. Among the challenged hens housed on slats, Campylobacter was recovered from 44% of the cecum, 6% of the spleen, 19% of the LGB, 12% of the LRT, 6% of the URT, and 14% of the follicle samples. Among challenged hens housed on shavings, Campylobacter was recovered from 46% of the cecum, 8% of the LRT and URT, and 40% of the follicle samples. The overall results of this study indicate that the caged housing system provided the lowest horizontal transmission level of Salmonella and Campylobacter among egg-laying hens. PMID- 22312978 TI - Colonization of a marker and field strain of Salmonella enteritidis and a marker strain of Salmonella typhimurium in vancomycin-pretreated and nonpretreated laying hens. AB - This study was conducted to evaluate the influence of a vancomycin pretreatment on the ability of marker (nalidixic-acid resistant) Salmonella Enteritidis (SE(M)), field Salmonella Enteritidis (SE(E)), and marker Salmonella Typhimurium (ST(M)) strains to colonize within the intestinal and reproductive tracts and translocate to other organs of leghorn laying hens. In each of three trials, caged laying hens (76, 26, and 33 wk ofage) were divided into six groups designated to receive SE(M), SE(F), or ST(M), and half were pretreated with vancomycin (n = 11-12 hens). Vancomycin-treated hens received 10 mg vancomycin in saline/kilogram body weight orally for 5 days to inhibit Gram-positive bacteria within the intestines. On Day 6, all hens were concurrently challenged by oral, intravaginal, and intracolonal routes with Salmonella and placed into separate floor chambers by Salmonella strain. Two weeks postinoculation, all hens were euthanatized and the ceca, spleen, liver/gall bladder (LGB), upper (URT), and lower (LRT) reproductive tracts, and ovarian follicles were aseptically collected, and analyzed for Salmonella. Results did not differ for the three hen's ages and were therefore combined. The vancomycin pretreatment also had no significant effect on the colonization ability of SE(M), SE(F) or ST(M), and therefore results were combined within Salmonella strain. The marker strain of Salmonella Enteritidis was recovered from 21% of ceca, 4% of LGB, 9% of LRT, and 17% of the fecal samples. The field strain of Salmonella Enteritidis was recovered from 88% of ceca, 96% of spleen, 92% of LGB, 30% of LRT, 4% of URT, 13% of follicle, and 42% of the fecal samples. The marker strain of Salmonella Typhimurium was recovered from 100% of ceca, 74% of spleen, 91% of LGB, 30% of LRT, 9% of URT, 9% of follicle, and 100% of the fecal samples. Among ceca, spleen, LGB, and fecal samples, SE(F) and ST(M) colonization was significantly greater than SE(M) colonization. Overall prevalence of Salmonella in the reproductive tracts of challenged hens was relatively low, ranging from 4% to 30%. PMID- 22312979 TI - Influenza A virus surveillance in live-bird markets: first report of influenza A virus subtype H4N6, H4N9, and H10N3 in Thailand. AB - A one-year influenza A survey was conducted in 10 live bird markets (LBMs) in H5N1 high-risk areas in Thailand from January to December 2009. The result from the survey showed that the occurrence of influenza A virus (IAV) in LBMs was 0.36% (19/5304). Three influenza A subtypes recovered from LBMs were H4N6 (n = 2), H4N9 (n = 1), and H10N3 (n = 16) from Muscovy ducks housed in one LBM in Bangkok. These influenza subtypes had never been reported in Thailand, and therefore such genetic diversity raises concern about potential genetic reassortment of the viruses in avian species in a particular setting. Two influenza A subtypes (H4N6 and H4N9) were isolated from oropharyngeal and cloacal swabs of the same duck, suggesting coinfection with two influenza subtypes and possible genetic reassortment in the bird. In addition, H10N3 infection in ducks housed in the same LBM was observed. These findings further support that LBMs are a potential source of IAV transmission and genetic reassortment. PMID- 22312980 TI - Moving-average trigger for early detection of rapidly increasing mortality in caged table-egg layers. AB - Rapidly increasing and unexplained mortality in commercial poultry flocks may signal the presence of a highly transmissible and reportable disease. Activation of an infectious-disease surveillance system occurs when a key production parameter, i.e., mortality, changes. Various triggers have been proposed to alert producers when mortality exceeds normal limits for a given production system to enable early detection of such diseases. In this article we demonstrate that a simple moving-average trigger is useful for detecting any disease syndrome in caged table-egg layer flocks that manifests itself as sudden, rapidly increasing mortality. We superimposed HPAI disease mortality output data derived from a disease transmission model and from a naturally occurring HPAI outbreak onto normal mortality data from 12 healthy commercial egg-layer flocks, and compared the performance of 7-day moving-average triggers to previously proposed triggers. The moving-average trigger is more efficient, resulting in fewer false-positive alerts and an earlier time to disease detection. It can be easily calculated by using a computer spreadsheet providing only 7 days of mortality data and can be practically and inexpensively implemented by large commercial poultry integrators. A moving-average trigger can be an active component of a production based surveillance system. PMID- 22312981 TI - Identification and characterization of H2N3 avian influenza virus from backyard poultry and comparison with novel H2N3 swine influenza virus. AB - In early 2007, H2N3 influenza virus was isolated from a duck and a chicken in two separate poultry flocks in Ohio. Since the same subtype influenza virus with hemagglutinin (H) and neuraminidase (N) genes of avian lineage was also identified in a swine herd in Missouri in 2006, the objective of this study was to characterize and compare the genetic, antigenic, and biologic properties of the avian and swine isolates. Avian isolates were low pathogenic by in vivo chicken pathogenicity testing. Sequencing and phylogenetic analyses revealed that all genes of the avian isolates were comprised of avian lineages, whereas the swine isolates contained contemporary swine internal gene segments, demonstrating that the avian H2N3 viruses were not directly derived from the swine virus. Sequence comparisons for the H and N genes demonstrated that the avian isolates were similar but not identical to the swine isolates. Accordingly, the avian and swine isolates were also antigenically related as determined by hemagglutination inhibition (HI) and virus neutralization assays, suggesting that both avian and swine isolates originated from the same group of H2N3 avian influenza viruses. Although serological surveys using the HI assay on poultry flocks and swine herds in Ohio did not reveal further spread of H2 virus from the index flocks, surveillance is important to ensure the virus is not reintroduced to domestic swine or poultry. Contemporary H2N3 avian influenza viruses appear to be easily adaptable to unnatural hosts such as poultry and swine, raising concern regarding the potential for interspecies transmission of avian viruses to humans. PMID- 22312982 TI - Variation in Salmonella enteritidis RAPD-PCR patterns may not be due to genetic differences. AB - Salmonella Enteritidis is a leading cause of gastroenteritis associated with consumption of contaminated poultry meat and eggs. Because pulsed-field gel electrophoresis (PFGE) has limited utility in distinguishing between clonal Salmonella Enteritidis isolates, random amplified polymorphic DNA (RAPD) PCR has been recommended as an alternative molecular fingerprinting tool. This study's objective was to determine whether increasing PCR stringency would improve the repeatability of RAPD DNA patterns based on assessment of target sites within the genome. An in silico PCR was performed to predict amplification products from an Salmonella Enteritidis genome sequence for three different RAPD primers (1247, 1283, and OPA4) and to determine whether any primer would be more likely to amplify variable regions within the genome. A comparison of within- and between isolate similarities in RAPD patterns was performed using primer 1247, which was predicted by in silico analysis to yield a variable size range of amplicons. In order to reduce artifactual variability associated with the method, three different methods for template preparation were evaluated. All were found to provide comparable results with respect to the similarities observed with repeated analyses of the same Salmonella Enteritidis isolates (n = 18, P = 0.91). Although the median within-isolate similarity (76.0%) was significantly greater than the median between-isolate similarity (66.7%; P = 0.001), duplicate RAPD-PCR runs of the same Salmonella Enteritidis isolates produced DNA patterns that ranged in similarity between 61.5 and 100%. These results indicate that the repeatability of RAPD-PCR is insufficient to distinguish genetic differences among related and unrelated Salmonella Enteritidis isolates. PMID- 22312983 TI - Serologic detection of duck enteritis virus using an indirect ELISA based on recombinant UL55 protein. AB - A recombinant UL55 protein (pUL55) of duck enteritis virus (DEV), produced in Escherichia coli, was tested for diagnostic applicability in an indirect enzyme linked immunosorbent assay (1-ELISA) as a coating antigen. Serum dilutions of 1:6400 (0.025microg) are the maximum detection limits of the pUL55-ELISA, according to the determined cut-off value of 0.330. Antigenic cross-reactivity investigation in heterologous sera of ducks failed to provide evidence that other viruses of ducks could hamper the serodiagnosis of DEV, and the inhibition assay revealed that the specific binding of antigen and antibody can be inhibited by pUL55, both of which demonstrated a good specificity of the established pUL55 ELISA. This assay was further validated by comparison with a commercial 1-ELISA based on DEV (DEV-ELISA) and a neutralization test (NT). The results suggested that the sensitivity of pUL55-ELISA was almost as good as DEV-ELISA but was much higher than NT. The established pUL55-ELISA is a rapid, simple, sensitive, specific, and inexpensive serodiagnosis for detecting antibodies against DEV and has a potential to complement the traditional assays for serodiagnosis of DEV; it can be used as a diagnosis alternative candidate for serologic surveillance of DEV infection. PMID- 22312984 TI - Pandemic H1N1 influenza virus in Chilean commercial turkeys with genetic and serologic comparisons to U.S. H1N1 avian influenza vaccine isolates. AB - Beginning in April 2009, a novel H1N1 influenza virus caused acute respiratory disease in humans, first in Mexico and then around the world. The resulting pandemic influenza A H1N1 2009 (pH1N1) virus was isolated in swine in Canada in June 2009 and later in breeder turkeys in Chile, Canada, and the United States. The pH1N1 virus consists of gene segments of avian, human, and swine influenza origin and has the potential for infection in poultry following exposure to infected humans or swine. We examined the clinical events following the initial outbreak of pH1N1 in turkeys and determined the relatedness of the hemagglutinin (HA) gene segments from the pH1N1 to two H1N1 avian influenza (AI) isolates used in commercial turkey inactivated vaccines. Overall, infection of turkey breeder hens with pH1N1 resulted in -50% reduction of egg production over 3-4 weeks. Genetic analysis indicated one H1N1 AI vaccine isolate (Alturkey/North Carolina/17026/1988) contained approximately 92% nucleotide sequence similarity to the pH1N1 virus (A/Mexico/4109/2009); whereas, a more recent AI vaccine isolate (A/ swine/North Carolina/00573/2005) contained 75.9% similarity. Comparison of amino acids found at antigenic sites of the HA protein indicated conserved epitopes at the Sa site; however, major differences were found at the Ca2 site between pH1N1 and A/ turkey/North Carolina/127026/1988. Hemagglutinin inhibition (HI) tests were conducted with sera produced in vaccinated turkeys in North Carolina to determine if protection would be conferred using U.S. AI vaccine isolates. HI results indicate positive reactivity (HI titer > or = 5 log2) against the vaccine viruses over the course of study. However, limited cross-reactivity to the 2009 pH1N1 virus was observed, with positive titers in a limited number of birds (6 out of 20) beginning only after a third vaccination. Taken together, these results demonstrate that turkeys treated with these vaccines would likely not be protected against pH1N1 and current vaccines used in breeder turkeys in the United States against circulating H1N1 viruses should be updated to ensure adequate protection against field exposure. PMID- 22312985 TI - Concomitant turkey herpesvirus-infectious bursal disease vector vaccine and oil adjuvanted inactivated Newcastle disease vaccine administration: consequences for vaccine intake and protection. AB - Hatchery vaccination protocols in day-old chicks are designed to provide early priming and protection against several poultry diseases including, but not limited to, Marek's disease (MD), infectious bursal disease (IBD), and Newcastle disease (ND). The constraint of concomitant administration of live MD and IBD vaccines plus ND inactivated oil-adjuvanted vaccines (IOAVs) requires improvements in vaccine technology. Single-needle concomitant subcutaneous (SC) application of IBD/MDV and killed NDV vaccine and the use of viral vectors for expression of immunogenic proteins are a current trend in the industry. The objective of this work was to assess the compatibility of a turkey herpesvirus (HVT)-infectious bursal disease (vHVT-IBD) vector vaccine applied simultaneously with IOAV and to evaluate the consequences for vaccine intake, the need for additional immunizations with the respective vaccines, and protection. Five separate trials were performed using double- and/or single-needle injectors. The levels and persistence of vaccine intake, serologic response, vHVT-IBD virus combination with the MD Rispens strain, and/or live NDV vaccination were also assessed. Histopathology and PCR at injection sites showed adequate vaccine intake detected up to 44 days postvaccination. Serologic evidence of vaccine priming was observed, and all vaccinated groups differed (P < 0.05) from the control at different time points. MD, NDV, and IBD protection results after concomitant double-shot single-needle vaccination were near 85%, 95%, and 100%, respectively. Taken together the results indicate no deleterious effects on the efficacy of the vHVT-IBD vaccine monitored by vaccine intake, serologic and challenge results, and combinations after concomitant live/killed vaccination, suggesting the suitability of its use in hatchery vaccination. All types of injectors used as well as injection techniques, vaccines injected separately or together, gave the same results. PMID- 22312986 TI - Avian influenza and Newcastle disease in three risk areas for H5N1 highly pathogenic avian influenza in Mali, 2007-2008. AB - Our survey aimed to investigate avian influenza (AI) and Newcastle disease (ND) prevalence and risk factors in three areas of Mali at risk for occurrence of H5N1 highly pathogenic avian influenza. Blood samples and cloacal and oropharyngeal swabs were collected from 1470 birds between February 2007 and May 2008 and were tested by commercial enzyme-linked immunosorbent assay to detect antibodies and real-time reverse-transcription (rRT)-PCR to detect virus. Risk factors associated with seropositivity or positive rRT-PCR were identified by random effect logistic regression. AI seroprevalence was significantly lower in birds from commercial farms (0%) than in village backyard birds (3.1%). For backyard birds, no individual risk factors (species, age, sex) were identified, but birds in the Mopti area in the Sahelian zone, where millions of wild birds migrate, were more seropositive than in the Sikasso area in the Sudano-Guinean zone (odds ratio [OR] = 2.0, P = 0.051). Among backyard birds nonvaccinated against ND, ND seroprevalence was 58.4%, and the odds of seropositivity was 2.0 higher in chickens than in ducks, 1.7 higher in females than in males, 3.1 higher in adults than in young birds, and 3.0 higher in poultry from the Sikasso area than from the Mopti area (P < 0.01 in all cases). Prevalence established by rRT-PCR was low for both AI virus (1.1%) and ND virus (2.6%) and was associated with no risk factors for AI but was higher in chickens than in ducks (OR = 5.3, P = 0.05) and in the Sikasso area than in the Mopti area (OR = 3.4, P = 0.027) for ND. For AI and ND, prevalence assessed by serology or rRT-PCR varied over time, although seasonal and interannual variation could not be clearly distinguished. The intracluster correlation coefficient for serologic data was low for AI (0.014) and higher for ND (0.222). These results are useful to optimize surveillance and control strategy for notifiable avian diseases in African countries with similar agroecological and resource-limited contexts. PMID- 22312987 TI - Genetic variation of highly pathogenic H5N1 avian influenza viruses in Vietnam shows both species-specific and spatiotemporal associations. AB - Domestic poultry act as a reservoir for persistent H5N1 endemicity in Vietnam, and the circulation of poultry flocks across farms and to market is thought to drive the spatial movement and evolution of avian influenza viruses. Using a dataset of complete or nearly full genomic sequences from highly pathogenic H5N1 avian influenza viruses collected in domestic poultry in Vietnam from 2003 to 2007, we explore potential differences in genetic characteristics according to species of isolation and the spatiotemporal characteristics of the viruses. Clustering algorithms and ANOVA indicate that H5N1 viruses in Vietnam show differences in the amount of genetic change that chicken viruses experience as compared to duck viruses, with duck viruses showing higher rates of molecular evolution on all eight of influenza's gene segments. There also exist distinct patterns of genetic differentiation according to the year in which they were isolated. These findings suggest that genetic evolution of avian influenza viruses is continuous through time but could also be mediated by the species in which the viruses occur, information that has implications for prevention efforts. PMID- 22312988 TI - Avian influenza adenovirus-vectored in ovo vaccination: target embryo tissues and combination with Marek's disease vaccine. AB - We investigated embryo tissues targeted by replication competent adenovirus (Ad) free recombinant Ad expressing a codon-optimized avian influenza (AI) H5 gene from A/turkey/WI/68 (AdH5) when injected into 18-day embryonated eggs. We also evaluated the effects of concurrent in ovo vaccination with the experimental AdH5 vaccine and commercially available Marek's disease virus (MDV) vaccine combinations Rispens/turkey herpesvirus (HVT) or HVT/SB-1. Computed tomography indicates that in ovo injection on day 18 of incubation places the solution in the amnion cavity, allantoic cavity, or both. Ad DNA was consistently detected in the chorioallantoic membranes as well as in the embryonic bursa of Fabricius, esophagus, and thymus 3 days postinoculation. H5 expression in these tissues also was detected by immunofluorescence assay. These results indicate possible swallowing of vaccine virus contained in the amnion. In contrast, vaccine localization in the allantoic fluid would have allowed bursal exposure through the cloaca. When the AdH5 vaccine was used in combination with MDV, chickens responding to the AdH5 vaccine had similar AI antibody levels compared with AdH5 only-vaccinated birds. However, combined vaccinated groups showed reduced vaccine coverage to AI, suggesting some level of interference. The combination of AdH5 with MDV Rispens/HVT affected the vaccine coverage to AI more severely. This result suggests that the replication rate of the more aggressive Rispens strain of serotype 1 may have interfered with the Ad-vectored vaccine. Increasing the Ad concentration produced similar AI antibody titers and AI vaccine coverage when applied alone or in combination with the HVT/SB-1 vaccine. Ad DNA was detected in hatched chickens 2 days after hatch but was undetectable on day 9 after hatch. MDV DNA was detected in feather follicles of all vaccinated birds at 12 days of age. Thus, Ad-vector vaccination does not interfere with the efficacy of MDV vaccination by using any of the commonly used vaccine strains. PMID- 22312989 TI - Evaluation of Nobuto filter paper strips for the detection of avian influenza virus antibody in waterfowl. AB - The utility of using Nobuto paper strips for the detection of avian influenza antibodies was examined in mallards (Anas platyrhynchos) experimentally infected with low pathogenic avian influenza viruses. Blood was collected 2 wk after infection and was preserved either as serum or whole blood absorbed onto Nobuto strips. Analysis of samples using a commercially available blocking enzyme-linked immunosorbent assay revealed comparable results (> or = 96% sensitivity for all methods) between sera stored at -30 C and the Nobuto strip preservation method even when the Nobuto strips were stored up to 3 mo at room temperature (RT). Significant differences were detected in the ratio of sample absorbance to negative control absorbance for Nobuto strips stored at RT compared with sera stored at -30 C, although these differences did not affect the ability of the test to reliably detect positive and negative samples. Nobuto strips are a convenient and sensitive alternative to the collection of serum samples when maintaining appropriate storage temperatures is difficult. PMID- 22312990 TI - Antiviral efficacy of oseltamivir against avian influenza virus in avian species. AB - Avian influenza is one of the most contagious viral diseases in bird species and, increasingly, interspecies transmission to mammalian species has been reported. Prevention and eradication of avian influenza virus (AIV) infection in birds may require vaccines as part of a comprehensive program including biosecurity, culling, diagnostics, and surveillance. However, for valuable bird species in zoos, novel eradication strategies are needed, including antiviral treatments. The present study evaluated the anti-influenza efficacy of the potent neuraminidase inhibitor oseltamivir in avian species using the orders Galliformes (chickens) and Anseriformes (ducks). Viral replication of low pathogenic AIV was significantly reduced in the chicken model and completely reduced in the duck model. Anti-influenza drug administration to valuable bird species with an appropriate extrapolation approach could be useful for control of AIV in combination with active surveillance and vaccination strategies. Further, evaluation of oseltamivir against highly pathogenic avian influenza (HPAI) using avian models would be needed to optimize the oseltamivir application guideline for HPAI control. PMID- 22312991 TI - Experimental inoculation of chickens with gull-derived low pathogenic avian influenza virus subtype H16N3 causes limited infection. AB - The infectivity, transmission, and pathogenicity potential of avian influenza virus (AIV) subtype H16N3, isolated from the European herring gull (Larus argentatus), was examined in chickens. Nineteen 6-wk-old commercial Lohmann white chickens were inoculated intranasally with 1 x 10(6) 50% egg infectious dose and clinical signs, humoral immune response, virus shedding, virus transmission, and pathologic changes in the respiratory tract were studied. Oropharyngeal and cloacal swabs were collected for viral RNA detection by real-time reverse transcriptase-PCR (rRT-PCR). Sera were collected and examined for H16-specific antibodies using a hemagglutination inhibition test. Tissue samples from the nasal cavity, trachea, and lung were collected at postmortem examination for histopathology and viral RNA detection by rRT-PCR. In one bird, bilateral serous nasal discharge was observed at 2 days postinoculation (DPI) and viral RNA was detected in oropharyngeal swabs at 2 and 4 DPI. Viral RNA was also detected from the oropharynx of an additional bird at 5 DPI. Moreover, H16-specific antibodies were detected in sera from these two birds at 14 and 21 DPI. No viral RNA was detected from cloacal swabs, and no virus transmission between virus-inoculated chickens and noninoculated contact chickens was observed. Tissue samples from the nasal cavity, trachea and lung were negative for viral RNA and no gross or histopathologic lesions were observed in the virus-inoculated birds. These results indicate that gull-derived AIV subtype H16N3 causes only limited infection in chickens under experimental conditions. PMID- 22312992 TI - ERIC-PCR genotyping of emergent serovar C-1 isolates of Avibacterium paragallinarum from Mexico. AB - Between 2008 and 2010, 14 isolates of Avibacterium paragallinarum were identified as serovar C-1 in Mexico. All isolates were obtained from commercial laying hens suffering infectious coryza despite a history of vaccination. The enterobacterial repetitive intergenic consensus-based PCR genotyping showed that all isolates had a common pattern. Until recently, serovars A-1, A-2, B-1, and C-2 were the serovars prevalent in Mexico. Serovar C-1 has been identified in Japan and recently in the Americas in Ecuador. Our current study suggests that Av. paragallinarum serovar C-1 is an emerging serovar in Mexico. Our results also indicate that the Mexican isolates of Av. paragallinarum serovar C-1 may have a clonal relationship. Knowledge of the genetic diversity of Av. paragallinarum may be of value in understanding vaccine performance and identifying the best combination to achieve broader protection. PMID- 22312993 TI - High prevalence of antibiotic resistance in pathogenic Escherichia coli from large- and small-scale poultry farms in Bangladesh. AB - Antibiotic resistance in avian bacterial pathogens is a common problem in the Bangladesh poultry industry. The aim of the present study was to provide information on the present status of antibiotic resistance patterns in avian pathogenic Escherichia coli in Bangladesh. Of 279 dead or sick poultry of different ages, 101 pathogenic E coli strains isolated from broilers and layer hens with colibacillosis infections were screened to determine phenotypic expression of antimicrobial resistance against 13 antibiotics used in both veterinary and human medicine in Bangladesh. Of 101 pathogenic E. coli isolates, more than 55% were resistant to at least one or more of the tested compounds, and 36.6% of the isolates showed multiple-drug-resistant phenotypes. The most common resistances observed were against tetracycline (45.5%), trimethoprim sulphamethoxazole (26.7%), nalidixic acid (25.7%), ampicillin (25.7%), and streptomycin (20.8%). Resistance to ciprofloxacin (12.9%), chlormaphenicol (8.9%), nitrofurantoin (2%), and gentamicin (2%) was also observed, and none of the isolates were resistant to tigecycline as well as extended spectrum beta lactamase (ESBL) producers. One isolate was resistant to cefuroxime (1%), cefadroxil (1%), and mecillinam (1%) but was not an ESBL producer. Resistance rates, although significant in Bangladeshi isolates, were found to be lower than those reported for avian isolates from the Republic of Korea and clinical, avian, and environmental isolates from Bangladesh. The high level of antibiotic resistance in avian pathogens from Bangladesh is worrisome and indicates that widespread use of antibiotics as feed additives for growth promotion and disease prevention could have negative implications for human and animal health and the environment. PMID- 22312994 TI - Identification and phylogenetic diversity of parvovirus circulating in commercial chicken and turkey flocks in Croatia. AB - Phylogenetic diversity of parvovirus detected in commercial chicken and turkey flocks is described. Nine chicken and six turkey flocks from Croatian farms were tested for parvovirus presence. Intestinal samples from one turkey and seven chicken flocks were found positive, and were sequenced. Natural parvovirus infection was more frequently detected in chickens than in turkeys examined in this study. Sequence analysis of 400 nucleotide fragments of the nonstructural gene (NS) showed that our sequences had more similarity with chicken parvovirus (ChPV) (92.3%-99.7%) than turkey parvovirus (TuPV) (89.5%-98.9%) strains. Phylogenetic analysis grouped our sequences in two clades. Also, the higher prevalence of ChPV than TuPV in tested flocks was defined. The necropsy findings suggested a malabsorption syndrome followed by a preascitic condition. Further research of parvovirus infection, pathogenesis, and the possibility of its association with poult enteritis and mortality syndrome (PEMS) and runting and stunting syndrome (RSS) is needed to clarify its significance as an agent of enteric disease. PMID- 22312995 TI - Bovine rotavirus in turkeys with enteritis. AB - Rotaviruses are the main agents responsible for diarrhea in different animal species and for infantile gastroenteritis. These viruses have been isolated from various avian species and have often been associated with poult enteritis and mortality syndrome. Nevertheless, the knowledge of rotavirus infection in turkeys is scarce. Six group A rotavirus strains obtained from pooled enteric contents of diarrheic turkeys were isolated in MA-104 cell culture and typed as G(6)P(1), a typical bovine rotavirus genotype. Additionally, the electropherotypes showed a migration pattern identical to the Nebraska calf diarrhea virus, and the complete NSP4 gene phylogeny showed that all six strains segregated in the genotype E2. Taken together, these results point toward a cattle-to-turkey rotavirus transmission. As a conclusion, bovine-origin rotavirus can be found in turkeys, and this transmission route must now be considered for the improvement of the health status in turkey farms. PMID- 22312996 TI - Disseminated toxoplasmosis in black-footed penguins (Spheniscus demersus). AB - Three 1- to 3-mo-old black-footed penguins (Spheniscus Demersus) died within 24 hr of showing central nervous signs such as ataxia. The birds were housed in a baby penguin creche. At necropsy, peritonitis, pneumonia, hepatomegaly, splenomegaly, and renomegaly were evident. Histologically, the liver, lung, brain, and small intestine contained numerous tachyzoites and a few cysts of Toxoplasma. Immunohistochemistry identified the protozoal parasites as Toxoplasma gondii. Ultrastructurally, this was confirmed by the presence of many tachyzoites of T. gondii in the liver and lungs. PMID- 22312997 TI - Cerebral neuroblastoma and pituitary adenocarcinoma in two budgerigars (Melopsittacus undulatus). AB - Case 1: A tumor mass involving the rostral part of left cerebrum was found in a two-year-old female budgerigar (Melopsittacus undulatus) at necropsy. Histologically, the neoplastic cells were arranged in sheets or cords and occasionally showed nest growth patterns. These uniform tumor cells had a little cytoplasm and ovoid or round basophilic nuclei with clearly distinct cytoplasmic membranes. The tumor cells were strong diffusely immunostained with both neuron specific enolase (NSE) and neurofilament protein and partially for synaptophysin. They lacked chromogranin A, glial fibrillary acidic protein (GFAP), vimentin, S 100, and cytokeratin antigen expression. Moreover, they had no reaction to antibodies against pituitary hormones, such as adrenocorticotrophic hormone (ACTH), growth hormone, and prolactin. The histological and immunohistochemical examination determined the tumor as neuroblastoma. Case 2: An extremely enlarged pituitary mass was found above the sella turcica of a male budgerigar. It was soft and well delineated from the adjacent structures. On histological examination, this tumor consisted of a sheet of large closely packed polyhedral cells that had scant to a large amount of pale to strongly eosinophilic cytoplasm. The pleomorphic nuclei were apparently variable in shape, from small round hyperchromatic to very large vesicular forms. The cell boundaries were not clearly distinct. The multifocal immunolabelling of neoplastic cells for NSE, synaptophysin, GFAP, and ACTH appeared, whereas a few cells reacted with vimentin and S-100 and stained negative for other markers, which were also utilized for case 1. Histological and immunohistochemical findings led to identification of corticotroph adenocarcinoma in the pituitary gland. PMID- 22312998 TI - Glomerular lipidosis accompanied by renal tubular oxalosis in wild and laboratory reared Japanese rock ptarmigans (Lagopus mutus japonicus). AB - Glomerular lipidosis is a disease characterized by lipid accumulation in mesangial cells but that has not been fully investigated in avian species. We examined four wild and two laboratory-reared Japanese rock ptarmigans (Lagopus mutus japonicus)--an endangered avian species--presenting vacuolar deposits in the glomeruli. All cases had vacuolar deposits in the glomeruli. In the wild cases, fewer than 30% of all glomeruli were affected, compared with more than 90% in the laboratory-reared cases. In the wild cases, most deposits were mild and restricted to the mesangial areas of glomeruli. In the laboratory-reared cases, nearly all of the deposits covered entire glomeruli. Electron microscopy of mild deposits revealed vacuoles in the cytoplasm of mesangial cells. These vacuoles were positive for Sudan III, Sudan black B, oil red O, Nile blue, periodic acid Schiff, Schultz test, and digitonin stain and were negative for performaric acid Schiff stains. Based on these results, we diagnosed the glomerular lesion as glomerular lipidosis caused by uptake of low-density lipoprotein in mesangial cells. Except for one wild case, all cases exhibited renal tubular oxalosis. The severity of tubular oxalosis tended to be related to the severity of glomerular lipidosis: In cases of mild glomerular lipidosis, tubular oxalosis was also mild or absent. We therefore diagnosed the primary lesion as glomerular lipidosis accompanied by tubular oxalosis. The four wild cases came from different zones and therefore had no opportunities to interbreed and no common relatives. We believe these data support the hypothesis that glomerular lipidosis is a disease of the general population ofJapanese rock ptarmigans. This is the first report of glomerular lipidosis accompanied by renal tubular oxalosis in an avian species. PMID- 22312999 TI - Outbreak of cutaneous form of poxvirus on a commercial turkey farm caused by the species fowlpox. AB - The present report documents the occurrence of a poxvirus infection in commercial meat turkeys. The affected farm had six flocks, with a total of 11,680 birds at different ages; birds from two of these flocks were affected. The clinical picture was characterized by severe epithelial lesions and proliferations on the head and neck regions as reported for the cutaneous form of poxvirus infection. Except for these lesions, no adverse clinical signs or gross pathologic lesions were observed. Only a low number of birds was affected (n = 20) and no increase of mortality could be seen. Bacteriologic investigations from the lesions revealed multiresistant Staphylococcus aureus. Eosinophilic inclusions (Bollinger bodies) in histologic examinations in the cytoplasm of keratinocytes were noticeable. Typical pox virions were demonstrated by electron microscopy, and poxvirus was isolated on the chorioallantoic membrane of specific-pathogen-free chicken eggs. Further identification of the poxvirus species was carried out by PCR and sequencing, revealing an infection with the species fowlpox. Layers in vicinity of the turkey farm that also were affected by fowlpox were considered as potential source of infection. Although it is assumed that avian poxviruses are strongly species specific, the present case report reinforces the changing picture of poxvirus infections in turkeys. Furthermore, it supports the assumption of previous data that fowlpox virus has to be seen as recently emerging pathogen in turkeys. PMID- 22313000 TI - Inclusion body hepatitis caused by fowl adenovirus in broiler chickens in Japan, 2009-2010. AB - From January 2009 to June 2010, many broiler chicks suddenly died without clinical signs. The mortality rates were from 1.2% to 17.0% in affected flocks. Inclusion body hepatitis (IBH) was detected in 13 prefectures (northern, eastern, western, and southern areas) in Japan. The livers were enlarged and pale. The bursa of Fabricius and thymus had not atrophied. Multifocal necroses of hepatocytes with basophilic intranuclear inclusions were seen in the liver. Eosinophilic intranuclear inclusion bodies in hepatocytes were rare. Focal necrosis of acinar cells with basophilic intranuclear inclusions was found in the pancreas. Basophilic intranuclear inclusion bodies were detected in intact surface epithelial cells of gizzard and epithelial cells of the small intestine. The intranuclear inclusions of liver, pancreas, gizzard, and small intestine were stained positively for immunohistochemistry of fowl adenovirus (FAV) antigen. Ultrastructurally, basophilic intranuclear inclusions consisted of viral particles approximately 70 nm in diameter and arranged in a crystalline array. FAV was isolated from the liver of chickens affected with IBH. The serotype of most isolates was 2. This study suggests that IBH produced by FAV is epidemic in broiler chicks in Japan and that the present cases occurred as the primary disease without the association of infectious bursal disease virus or chicken anemia virus. PMID- 22313001 TI - Isolation and characterization of a novel H9N2 influenza virus in Korean native chicken farm. AB - An outbreak of avian influenza, caused by an H9N2 low-pathogenic avian influenza virus (AIV), occurred in a chicken farm and caused severe economic losses due to mortality and diarrhea. AIV was isolated and identified in a sample from an affected native Korean chicken. Genetic analysis of the isolate revealed a high sequence similarity to genes of novel reassortant H9N2 viruses isolated from slaughterhouses and live bird markets in Korea in 2008 and 2009. Animal challenge studies demonstrated that the replication kinetics and pathogenicity of the isolate were considerably altered due to adaptation in chickens. Vaccine protection studies indicated that commercial vaccine was not able to prevent virus shedding and clinical disease when chickens were challenged with the isolate. These results suggest that the novel H9N2 virus possesses the capacity to replicate efficiently in the respiratory system against vaccination and to cause severe disease in domestic chickens. The results also highlight the importance of appropriate updating of vaccine strains, based on continuous surveillance data, to prevent the possibility of a new H9N2 epidemic in Korea. PMID- 22313003 TI - Writing the scrip: integrated partnerships are the new medicine for hospital physician relations. PMID- 22313002 TI - Your 2012-2014 strategic plan: revised plan aims to further serve ACHE affiliates. PMID- 22313004 TI - Physician leadership development: a strategic imperative for integrated healthcare delivery. PMID- 22313005 TI - Ethical challenges and responsibilities of leaders. PMID- 22313006 TI - ACHE in 2011: pursuing excellence. PMID- 22313007 TI - Manage by getting out of the way. PMID- 22313008 TI - Work-life balance. PMID- 22313009 TI - Do your co-workers trust you? PMID- 22313010 TI - Fear of conflict: management and ethical costs: wanting to avoid conflict is natural but should not inhibit appropriate behavior. PMID- 22313011 TI - Art and science: an innovative art program aids in healing. PMID- 22313012 TI - Fields of green: an obesity prevention initiative: partnering with the community to reverse troubling obesity, hunger trends. PMID- 22313013 TI - Medicare entitlement reform: a snapshot: healthcare executives are encouraged to tune in to the discussion. PMID- 22313014 TI - Bringing your personal brand to life: an effective brand communicates your distinct value. PMID- 22313015 TI - Transforming healthcare: the board's role: investment in IT crucial to success. PMID- 22313016 TI - Leaders challenged to reduce cost, deliver more: targeted improvements are critical for creating a culture dedicated to efficiency and quality. PMID- 22313017 TI - Enhancing physician recruitment efforts: key approaches for attracting the right physician candidates. PMID- 22313018 TI - Hypoglycemia, but not glucose variability, relates to vascular function in children with type 1 diabetes. AB - BACKGROUND: Chronic sustained hyperglycemia unequivocally predicts vascular disease in diabetes. However, the vascular risk of glucose variability, including hypoglycemia, is uncertain. Vascular dysfunction is present in children with type 1 diabetes and is a critical precursor of atherosclerosis. We aimed to evaluate the relationship between glucose variability and vascular function in children with type 1 diabetes. SUBJECTS AND METHODS: Fifty-two type 1 diabetes subjects (14 [SD 2.7] years old, 25 males) had continuous glucose monitoring that included 48 h of data used to evaluate glucose variability (mean amplitude of glycemic excursions [MAGE] and other measurements) and hypoglycemia indices (glycemic risk assessment diabetes equation [GRADE] hypoglycemia, Low Blood Glucose Index [LBGI], and observed duration of hypoglycemia). Children with type 1 diabetes and 50 age- and gender-matched controls had assessments of vascular function (flow mediated dilatation [FMD] and glyceryl trinitrate-mediated dilatation [GTN]). RESULTS: Children with type 1 diabetes had lower FMD and GTN than controls (P=0.02 and P<0.001, respectively). GRADE hypoglycemia and LBGI were inversely related to FMD (r=-0.36, P=0.009 and r=-0.302, P=0.03, respectively) but did not relate to GTN. GRADE hypoglycemia was independently related to FMD (regression coefficient=-0.25+/-0.09, P=0.006). MAGE and other measurements of glucose variability measurements did not relate to FMD or GTN. CONCLUSIONS: Hypoglycemia, but not glucose variability, during continuous glucose monitoring relates to impaired vascular endothelial function in children with type 1 diabetes. Hypoglycemia may be an additional risk factor for early cardiovascular disease, but the effect of glucose variability, independent of glycosylated hemoglobin, on vascular function remains uncertain. PMID- 22313019 TI - Adsorption of doxorubicin on poly(methyl methacrylate)-chitosan-heparin-coated activated carbon beads. AB - Extracorporeal filter cartridges, filled with an activated carbon bead (ACB) adsorbent, have been used for removal of overdosed cancer drugs from the blood. Coatings on adsorbent matrices, poly(methyl methacrylate) (PMMA)/activated carbon bead and PMMA/chitosan/heparin/ACB composites, were tested to improve their biocompatibility and blood compatibility. PMMA coating on ACBs was accomplished in a straightforward manner using a PMMA solution in ethyl acetate. A one-step hybrid coating of ACBs with PMMA-anticoagulant heparin required the use of acetone and water co-solvents. Multilayer coatings with three components, PMMA, chitosan, and heparin, involved three steps: PMMA was first coated on ACBs; chitosan was then coated on the PMMA-coated surface; and finally, heparin was covalently attached to the chitosan coating. Surface morphologies were studied by scanning electron microscopy. X-ray photoelectron spectroscopy confirmed the SO(3)(-) group. Adsorption, of a chemotherapy drug (doxorubicin) from both water and phosphate-buffered saline, by the coated ACBs was examined. The adsorption isotherm curves were fitted using the Freundlich model. The current adsorption system might find potential applications in the removal of high-dose regional chemotherapy drugs while maintaining high efficiency, biocompatibility, and blood compatibility. PMID- 22313020 TI - Prevalence of gastroparesis before and after lung transplantation and its association with lung allograft outcomes. AB - The main cause of late morbidity and mortality after lung transplantation is bronchiolitis obliterans syndrome (BOS). This study assesses the prevalence of gastroparesis among lung-transplant recipients and its association with BOS. The files of 139 patients who underwent nuclear gastric emptying studies before and/or three and 12 months after lung transplantation were reviewed, and the correlation of gastric emptying time (GET) at each time point with the occurrence of acute rejection or BOS (stage 0p or higher) was evaluated. Delayed gastric emptying (DGE; t(1/2) > 90 min) was documented in 50% of patients before transplantation - 74% at three months and 63% at 12 months. Median pre-transplant t(1/2) was 108 min in patients who acquired BOS and 77 min in BOS-free patients (p = 0.022). Among patients with pre-transplant DGE, 58% were BOS-free at 24 months post-operatively and 37% at 36 months; corresponding rates in patients with normal motility were 78% and 63% (p = 0.084). On multiple regression analysis adjusting for other measures of upper gastrointestinal dysfunction, GET before or three months after transplantation was significantly associated with BOS (OR 1.05 [95% CI 1.01-1.09] and OR 1.001 [1.001-1.005] per minute t(1/2)). Gastroparesis is common in lung-transplant recipients and associated with the development of BOS. PMID- 22313021 TI - The effect of mild depression on time discrimination. AB - Depressed mood states affect subjective perceptions of time but it is not clear whether this is due to changes in the underlying timing mechanisms, such as the speed of the internal clock. In order to study depression effects on time perception, two experiments using time discrimination methods with short (<300 ms) and long (>1,000 ms) durations were conducted. Student participants who were categorized as mildly depressed by their scores on the Beck Depression Inventory were less able than controls to discriminate between two longer durations but were equally able to discriminate shorter intervals. The results suggest that mildly depressed or dysphoric moods do not affect pacemaker speed. It is more likely that depression affects the ability to maintain attention to elapsing duration. PMID- 22313022 TI - Total decontamination cost of the anthrax letter attacks. AB - All of the costs associated with decontamination following the 2001 anthrax letter attacks were summarized, estimated, and aggregated based on existing literature and news media reports. A comprehensive list of all affected structures was compiled. Costs were analyzed by building class and decontamination type. Sampling costs and costs of worker relocation were also included. Our analysis indicates that the total cost associated with decontamination was about $320 million. PMID- 22313023 TI - H-coil repetitive transcranial magnetic stimulation for treatment resistant major depressive disorder: An 18-week continuation safety and feasibility study. AB - OBJECTIVE: Evidence has shown that repetitive transcranial magnetic stimulation (rTMS) can be effective as an acute treatment for major depressive disorder (MDD). However, few studies have examined the safety and feasibility of rTMS as a long-term?continuation treatment. Deep-TMS is a novel tool enabling deeper stimulation than standard coils. The current study examined the safety and feasibility of repetitive deep-TMS continuation treatment for MDD over the course of 18 weeks, following 4 weeks of acute treatment. METHOD: A total of 29 MDD patients were enrolled in the study. rTMS sessions (20 Hz) were given for a total of 22 weeks, divided into: 4 weeks of acute daily treatments, followed by 18 weeks of continuation treatments. Clinical evaluations were performed weekly throughout the study. RESULTS: A significant decrease from baseline in Hamilton Depression Rating Scale (HDRS) score was found at the end of the acute phase, and maintained throughout the study (P < 0.0001). The Kaplan-Meier estimated probability of response was 46.15% (SE = 9.78%) at the end of the acute phase, and 81.12% (SE = 9.32%) at the end of the study (22 weeks). probability of remission at the end of the acute phase was 26.92% (SE = 8.70%) and 71.45% (SE = 10.99%) at the end of the study. Response in the acute phase was indicative of response in the continuation phases. The procedure was generally well tolerated and no adverse events were reported. CONCLUSION: The results suggest that H-coil deep-TMS administered continuation treatment can help maintain an antidepressant effect for 18 weeks, following 4 weeks of acute treatment. PMID- 22313024 TI - Effect of increasing hemoglobin cutoff in male donors and increasing interdonation interval in whole blood donors at a hospital-based blood donor center. AB - BACKGROUND: The NHANES-III survey found hemoglobin (Hb) concentrations of more than 13.5 g/dL and more than 12.0 g/dL in normal Caucasian males and females. In the United States, a Hb of least 12.5 g/dL is required for blood donation, which allows "anemic" males to donate while excluding "normal" females. Low Hb is the major cause of deferral in donors and deferrals are associated with decreased donor return rates. Additionally, frequent blood donations are associated with depletion of body iron stores. Analysis of the effect of various Hb cutoffs and interdonation intervals on our center's blood supply is presented. STUDY DESIGN AND METHODS: Whole blood donor data for a 12-month period were studied. Potential effects on the blood supply by increasing male Hb eligibility levels and/or increasing the interdonation interval were analyzed. RESULTS: A total of 13,519 individuals (females, 56%) donated 30,678 units (mean frequency, male 2.7 and females 2.1) with the majority (42%) donating once. Increasing the male Hb eligibility to at least 13.5 g/dL will decrease collections by 1457 (5%) units. In addition, decreasing the female Hb eligibility to at least 12.0 g/dL will result in total gain of 307 (1%) units. Considering 12-week interdonation interval and Hb eligibility of at least 13.5 g/dL (male) and at least 12.5 g/dL (female) results in decrease of 11% (3352) units. CONCLUSIONS: Increasing the Hb cutoff for male donors and/or interdonation interval for all donors will decrease available blood, some of which may be reduced by decreasing the Hb cutoff for females to at least 12.0 g/dL. As a majority of the donors donate only once with mean donation frequency being 2.4, it may be possible to overcome this shortfall by targeted recruitment of donors donating once. PMID- 22313025 TI - Synthesis of 3-substituted and 2,3-disubstituted quinazolinones via Cu-catalyzed aryl amidation. AB - CuI/4-hydroxy-L-proline catalyzed coupling of N-substituted o-bromobenzamides with formamide takes place at 80 degrees C, affording 3-substituted quinazolinones directly. Under these conditions other amides that were tested only provided simple coupling products, which can be converted into 2,3 disubstituted quinazolinones via HMDS/ZnCl(2) mediated condensative cyclization. PMID- 22313026 TI - Gender differences in health service utilization among Iraq and Afghanistan veterans with posttraumatic stress disorder. AB - BACKGROUND: Little is known about gender differences in healthcare use among newly returning veterans with posttraumatic stress disorder (PTSD). We investigated gender differences in Veterans Affairs (VA) medical center health service use among Iraq and Afghanistan veterans with PTSD with and without comorbid depression and alcohol use disorders (AUD). METHODS: Using VA administrative data, bivariate and multivariate statistics were used to examine gender differences in health service use among 159,705 Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans with PTSD seeking VA healthcare from October 7, 2001, to December 31, 2010. RESULTS: Female veterans with PTSD were more likely to be black and single and to have higher mental health, primary care, and emergency care use compared to men with PTSD. Men were more likely to have higher mental health inpatient use compared to women. Women and men with comorbid PTSD and depression or comorbid PTSD and AUD were more likely to have higher use in all domains compared to their counterparts with PTSD without these comorbid disorders. Women with comorbid PTSD and depression were 12.5 times more likely to have a mental health inpatient hospitalization compared to their female counterparts without depression and twice as likely to have a mental health hospitalization compared to men with comorbid PTSD and depression. CONCLUSIONS: Women with PTSD had higher use than men in almost all areas, as did all veterans with comorbid PTSD and depression and comorbid PTSD and AUD, regardless of gender. Better understanding these health service use differences will allow for targeted evaluation and integrated treatment interventions in veterans with PTSD. PMID- 22313027 TI - How does lifestyle intervention affect depressive symptoms? Results from the Finnish Diabetes Prevention Study. AB - AIMS: To assess the effect of lifestyle intervention on depressive symptoms during a 36-month randomized clinical trial designed to prevent Type 2 diabetes. METHODS: A total of 522 middle-aged participants, who were overweight or obese and had impaired glucose tolerance, were randomized to the lifestyle intervention or control group in the Finnish Diabetes Prevention Study. The intervention group received individualized counselling aimed at reducing weight and increasing physical activity. Depressive symptoms were measured using the Beck Depression Inventory among a subgroup of 140 participants. RESULTS: On study entry, the mean Beck Depression Inventory scores +/- sd were 6.8 +/- 5.6 in the intervention group and 6.7 +/- 5.5 in the control group. Beck Depression Inventory scores reduced during the intervention study: the mean +/- sd (95% CI) reduction was 0.90 +/- 4.54 (-1.99 to -0.19) scores in the intervention group and 0.75 +/- 4.47 (-1.80 to 0.31) in the control group, with no difference between the groups. In a stepwise linear multivariate regression analysis, the variables with the strongest associations with the change in Beck Depression Inventory scores were baseline Beck Depression Inventory scores, marital status, weight change and change of total energy intake (R(2) = 0.209, P < 0.001). CONCLUSIONS: Participation in the study lowered depression scores, with no specific group effect. Among the lifestyle changes, particularly successful reduction of body weight was associated with the greater reduction of depressive symptoms. Thus, regardless of the intensity of the treatment, the success in executing alterations in one's lifestyle and behaviour is associated with beneficial changes in mood. PMID- 22313028 TI - Bayesian enhanced meta-analysis of post-operative analgesic efficacy of additives for caudal analgesia in children. AB - BACKGROUND: The authors calculated the effect size for post-operative analgesia of three additives, clonidine, neostigmine, and tramadol to bupivacaine, ropivacaine, or levobupivacaine used for single-dose caudal extradural blockade in children. METHODS: A meta-analysis was performed for three end points of efficacy: the increase of time until administration of analgesic drugs, the proportion of patients requiring analgesic drugs during the initial 24 post operative hours, and the amounts of post-operative analgesic drugs. A Bayesian inference supporting direct statements about the probability of the magnitude of an effect was used to compare the effects size. RESULTS: Neostigmine increased the duration of analgesia by 9.96 h (95% confidence interval: 7.75 to 12.16), as compared with 3.68 h (2.65 to 4.7) with clonidine and 4.45 (2.84 to 6.07) with tramadol. There is a 95% probability that neostigmine increases the duration of post-operative analgesia by more than 8 h, clonidine by more than 2.8 h, and tramadol by more than 3.25 h, as compared with local anesthetics alone. The odds ratios for the proportion of patients requiring analgesic drugs were 0.22 [0.13 to 0.37] for clonidine and 0.28 [0.10 to 0.75] for neostigmine. With tramadol, there was no statistically significant difference. All three additives reduced the amounts of post-operative analgesic drugs. Neostigmine and tramadol increase the probability for post-operative nausea or vomiting (PONV). CONCLUSIONS: Neostigmine provides the longest post-operative analgesia. With clonidine, the duration of analgesia is shorter and sedation is increased, but the probability for PONV could be decreased. PMID- 22313030 TI - Dynamics of DNA methylation in aging and Alzheimer's disease. AB - Gene expression is modulated by epigenetic factors that come in varying forms, such as DNA methylation, histone modifications, microRNAs, and long noncoding RNAs. Recent studies reveal that these epigenetic marks are important regulatory factors in brain function. In particular, DNA methylation dynamics are found to be essential components of epigenetic regulation in the mammalian central nervous system. In this review, we provide an overview of the literature on DNA methylation in neurodegenerative diseases, with a special focus on methylation of 5-position of cytosine base (5mC) and hydroxymethylation of 5-position of cytosine base (5hmC) in the context of neurodegeneration associated with aging and Alzheimer's disease. PMID- 22313031 TI - Fibroblast growth factor receptor 4 polymorphisms and susceptibility to coronary artery disease. AB - Fibroblast growth factors (FGFs) and their receptors (FGFRs) play crucial roles in vascular smooth muscle cell proliferation and atherosclerosis and, therefore, may potentially affect the development of coronary artery disease (CAD). FGFR4 rs351855 (Gly388Arg) polymorphism has shown to be a risk factor for many diseases. The aim of this study was to investigate the association between FGFR4 polymorphisms and the susceptibility to CAD in the Chinese population. Two polymorphisms, rs351855 (Gly388Arg) and rs641101, were detected by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing in 687 CAD cases and 732 age-matched controls. Data were analyzed using the chi square test. Results showed that frequencies of GA genotype, AA genotype, and A allele in rs351855 (Gly388Arg) polymorphism were significantly lower in CAD patients than in controls (odds ratio (OR)=0.78, 95% confidence intervals (CIs): 0.62-0.98, p=0.034; OR=0.58, 95% CI: 0.42-0.80, p=0.001; and OR=0.77, 95% CI: 0.66-0.90, p=0.001, respectively). The rs641101 polymorphism did not show any correlation with CAD. Haplotype analysis revealed that rs351855 and rs641101 AG haplotype also had lower frequency in CAD patients (OR=0.79, 95% CI: 0.67-0.92, p=0.002). Our data suggested that the FGFR4 rs351855 (Gly388Arg) polymorphism and AG haplotype (rs351855 and rs641101) could act as protective factors against CAD in the Chinese population and indicated that a single gene polymorphism could have diverse functions in different diseases. PMID- 22313032 TI - A new incorporation mechanism for trivalent actinides into bioapatite: a TRLFS and EXAFS study. AB - One of the most toxic byproducts of nuclear power and weapons production is the transuranics, which have a high radiotoxicity and long biological half-life due to their tendency to accumulate in the skeletal system. This accumulation is inhomogeneous and has been associated with the chemical properties and structure of the bone material rather than its location or function. This suggests a chemical driving force to incorporation and requires an atomic scale mechanistic understanding of the incorporation process. Here we propose a new incorporation mechanism for trivalent actinides and lanthanides into synthetic and biologically produced hydroxyapatite. Time-resolved laser fluorescence spectroscopy and extended X-ray absorption fine structure have been used to demonstrate that trivalent actinides and lanthanides incorporate into the amorphous grain boundaries of apatite. This incorporation site can be used to explain patterns in uptake and distribution of radionuclides in the mammalian skeletal system. PMID- 22313033 TI - iTRAQ analysis of a cell culture model for malignant transformation, including comparison with 2D-PAGE and SILAC. AB - To study human cancer development, cell culture models for malignant transformation can be used. In 1999 Hahn and Coworkers introduced such a model system and established herewith a basis for research on human tumorigenesis. Primary human fibroblasts are sequentially transduced with defined genetic elements (hTERT, SV40 ER, and H-RasV12), resulting in four defined cell lines, whereby the last has a fully transformed phenotype. In order to get a deeper insight into the molecular biology of human tumorigenesis, we compared the proteomes of these four cell lines following a multimethod concept. At the beginning we assumed SILAC and sample fractionation with COFRADIC is the method of choice to analyze the cell culture model for malignant transformation. Here, the compared samples are combined before sample preparation, thus avoiding differences in sample preparation, and using COFRADIC notably reduces sample complexity. Because 2D-PAGE is a standard method for the separation and visualization of closely related proteomes, we decided to analyze and compare the proteomes of these four cell lines in a first approach by differential 2D-PAGE. Surprisingly, we discovered much more unique results with iTRAQ and sample fractionation with SCX than with the combination of 2D-PAGE and SILAC-COFRADIC. Moreover, iTRAQ outperforms the other strategies not only in number of yielded results but also in analysis time. Here, we present the iTRAQ quantification results and compare them with the results of 2D-PAGE and SILAC-COFRADIC. We found changes in the protein level at each transition. Thereby, SV40 has the strongest impact on the proteome. In detail we identified 201 regulated proteins. Beside others, these proteins are involved in cytoskeleton, RNA processing, and cell cycle, such as CDC2, hnRNPs, snRNPs, collagens, and MCM proteins. For example, MCM proteins are up-regulated and collagens are down-regulated due to SV40 ER expression. Furthermore we made the observation that proteins containing the same domain have analogous regulation profiles during malignant transformation. For instance, several proteins containing a CH or LIM domain are down-regulated. Moreover, by this study and the defined cell culture model, changes could be clearly matched to specific steps during tumorigenesis. PMID- 22313034 TI - Bilingual effects on cognitive and linguistic development: role of language, cultural background, and education. AB - A total of 104 six-year-old children belonging to 4 groups (English monolinguals, Chinese-English bilinguals, French-English bilinguals, Spanish-English bilinguals) were compared on 3 verbal tasks and 1 nonverbal executive control task to examine the generality of the bilingual effects on development. Bilingual groups differed in degree of similarity between languages, cultural background, and language of schooling. On the executive control task, all bilingual groups performed similarly and exceeded monolinguals; on the language tasks the best performance was achieved by bilingual children whose language of instruction was the same as the language of testing and whose languages had more overlap. Thus, executive control outcomes for bilingual children are general but performance on verbal tasks is specific to factors in the bilingual experience. PMID- 22313035 TI - Prevalence and correlates of psychotropic medication use among older adults in Israel: cross-sectional and longitudinal findings from two cohorts a decade apart. AB - OBJECTIVES: To assess: (1) changes in use of psychotropic medications across two cohorts, 10 years apart, of community-dwelling elderly and the socio-demographic, physical and mental health correlates of their use; and (2) changes in psychotropic medication use over 3.5 years follow-up. METHODS: Data were taken from two national surveys of the Israeli Jewish population aged 75-94, which, respectively, sampled two cohorts in 1989 (n=1200) and again in 1999 (n=421). Psychotropic medications were assessed from the list of all medications recorded during a face-to-face interview. The current analysis focused on two medication groups: anxiolytics and sedatives/hypnotics and antidepressants. RESULTS: Sedatives/hypnotics and anxiolytics use increased from 22.2% in 1989 to 25.4% in 1999 and antidepressants from 3.8% to 4.8% (both nonsignificantly) corresponding to a decline in the health profile of community-dwelling older adults. Similar patterns of associations were observed for socio-demographics, physical, and mental health status indicators with the use of psychotropic medications across the two cohorts. The pooled multivariate analysis showed significantly higher use of sedative/hypnotics and anxiolytics among women and lower use among religious elderly. Additional risk factors were sleeping problems, number of other medications, depressive symptoms, and traumatic life events. Antidepressants use was related to a higher education, ADL disability, and depressive symptoms. Longitudinally, use of psychotropic medications was not significantly different among participants who were followed again after 3.5 years. CONCLUSIONS: Sedative/hypnotics and anxiolytics use was relatively high while antidepressants use was low even among depressed elderly suggesting that some depressed elderly were treated inappropriately with benzodiazepines. PMID- 22313036 TI - Eye movements reveal rapid concurrent access to factual and counterfactual interpretations of the world. AB - Imagining a counterfactual world using conditionals (e.g., If Joanne had remembered her umbrella . . .) is common in everyday language. However, such utterances are likely to involve fairly complex reasoning processes to represent both the explicit hypothetical conjecture and its implied factual meaning. Online research into these mechanisms has so far been limited. The present paper describes two eye movement studies that investigated the time-course with which comprehenders can set up and access factual inferences based on a realistic counterfactual context. Adult participants were eye-tracked while they read short narratives, in which a context sentence set up a counterfactual world (If . . . then . . .), and a subsequent critical sentence described an event that was either consistent or inconsistent with the implied factual world. A factual consistent condition (Because . . . then . . .) was included as a baseline of normal contextual integration. Results showed that within a counterfactual scenario, readers quickly inferred the implied factual meaning of the discourse. However, initial processing of the critical word led to clear, but distinct, anomaly detection responses for both contextually inconsistent and consistent conditions. These results provide evidence that readers can rapidly make a factual inference from a preceding counterfactual context, despite maintaining access to both counterfactual and factual interpretations of events. PMID- 22313037 TI - Pre-clinical pharmacokinetics of the acridine antitumour candidate AC04 and its 1 oxo-metabolite plasma profile. AB - This work aimed to investigate plasma pharmacokinetics and tissue distribution of a new acridine derivative 5-acridin-9-ylmethylene-3-(4-methyl-benzyl) thiazolidine-2,4-dione (AC04) and its 1-oxo-AC04 metabolite disposition in Wistar rats. After a single AC04 1.5 mg/kg intravenous (i.v.) bolus dose, blood samples were taken up to 120 h. Plasma samples were deproteinization, and AC04 and metabolite were quantified by validated liquid chromatography in tandem with mass spectrometry method. Protein binding was determined by ultrafiltration. AC04 tissue disposition was evaluated after i.v. bolus dose. Individual AC04 concentration-time profiles were best fitted by a two-compartment model showing CL(tot) of 3.4 +/- 3.4 L/h/kg, Vd(SS) of 137.9 +/- 91.4 L/kg, AUC(0-infinity) of 788 +/- 483 ng.h/mL and a t(1/2) of 45.5 +/- 31.5 h. Protein binding was 98.1 +/- 1.6%. AC04 showed higher penetration into the lung, spleen and liver, with AUC(0 96) of 798,443, 263,211 and 303,722 ng.h/mL, respectively. The 1-oxo-AC04 metabolite represented 10% of AC04 plasma concentration, showing a t(1/2) of 23.2 +/- 10.4 h. These results suggest that, despite the small free plasma fraction, AC04 penetrates extensively reaching high concentrations in most tissues residing for a long time, which is important for its activity on solid tumours. All results combined indicate that AC04 is potentially a good antitumour candidate. PMID- 22313038 TI - Different effects of proton pump inhibitors and famotidine on the clopidogrel metabolic activation by recombinant CYP2B6, CYP2C19 and CYP3A4. AB - Inhibitory potential of proton pump inhibitors (PPIs) and famotidine, an H(2) receptor antagonist, on the metabolic activation of clopidogrel was evaluated using recombinant CYP2B6, CYP2C19 and CYP3A4. Formation of the active metabolite from an intermediate metabolite, 2-oxo-clopidogrel, was investigated by liquid chromatography-tandem mass spectrometry and three peaks corresponding to the pharmacologically active metabolite and its stereoisomers were detected. Omeprazole potently inhibited clopidogrel activation by CYP2C19 with an IC(50) of 12.8 MUmol/L and more weakly inhibited that by CYP2B6 and CYP3A4. IC(50) of omeprazole for CYP2C19 and CYP3A4 was decreased about two- and three-fold, respectively, by 30-min preincubation with NADPH. Lansoprazole, esomeprazole, pantoprazole, rabeprazole and rabeprazole thioether, a major metabolite, also inhibited metabolic activation by CYP2C19, with an IC(50) of 4.3, 8.9, 48.3, 36.2 and 30.5 MUmol/L, respectively. In contrast, famotidine showed no more than 20% inhibition of clopidogrel activation by CYP2B6, CYP2C19 and CYP3A4 at up to 100 MUmol/L and had no time-dependent CYP2C19 and CYP3A4 inhibition. These results provide direct evidence that PPIs inhibit clopidogrel metabolic activation and suggest that CYP2C19 inhibition is the main cause of drug-drug interaction between clopidogrel and omeprazole. Famotidine is considered as a safe anti-acid agent for patients taking clopidogrel. PMID- 22313039 TI - Abnormal sebaceous gland differentiation in 10 kittens ('sebaceous gland dysplasia') associated with generalized hypotrichosis and scaling. AB - A rare congenital dermatosis, characterized by progressive hypotrichosis with variable scaling and crusting, occurred in 10 short-haired kittens in North America and Europe. Lesions appeared at between 4 and 12 weeks of age, commencing on the head and becoming generalized. The tail was spared in two kittens. Generalized scaling was mild to moderate, often with prominent follicular casts. Periocular, perioral, pinnal and ear canal crusting was occasionally severe. The skin was thick and wrinkled in two kittens. Histologically, the main lesion was abnormal sebaceous gland morphology. Instead of regular differentiation from basal cells to mature sebocytes, the glands were composed of a haphazard collection of undifferentiated basaloid cells, some partly vacuolated and a few containing eosinophilic globules. Mitotic figures and apoptotic cells were present in an irregularly thickened follicular isthmus. Lymphocytic mural folliculitis and mild sebaceous adenitis were rare. Orthokeratotic hyperkeratosis and follicular casts were present. Hair follicles were of normal density and were mostly in anagen, but some contained malacic hair shafts. Perforating folliculitis, leading to dermal trichogranuloma formation, occurred occasionally. Further biopsy samples taken at 2 years and at 3 and 4 years, respectively, from two kittens revealed similar but often more severe sebaceous gland lesions. Hair follicles were smaller, with many in telogen. The young age of onset suggests a genetic defect interfering with sebaceous and, possibly, follicular development. These lesions are discussed with reference to studies of mouse mutants in which genetic defects in sebaceous differentiation cause a similar phenotype of hyperkeratosis and progressive alopecia. PMID- 22313040 TI - Absence of acute adverse in vitro effects on aged AS-1 red blood cells and thawed plasma after prolonged exposure to 13.56-MHz radio energy. AB - BACKGROUND: There is growing interest in radio frequency identification (RFID) technology for tracking blood products to improve productivity and safety in the transfusion medicine supply chain. We conducted a limited study to assess the temperature and biologic effects after extreme exposure to 13.56-MHz RF radiation on aged red blood cells (aRBCs) nearing their 42-day life and three types of thawed plasma (TP). STUDY DESIGN AND METHODS: Using a Food and Drug Administration-approved limit test protocol, test units of both aRBCs and three types of TP were subjected to high levels of RF energy for an extended duration to assess worst-case effects compared to minimally exposed control units. Three replications were performed for each product type. RESULTS: Hemolysis after 23 to 25 hours of RF energy exposure was less than 0.3% for all test and control aRBC units and well within the 1% or less acceptance criterion. Both biologic test and temperature increase results were within acceptance criteria and consistent with earlier tests on 6- to 9-day RBCs, with no detectable acceleration in cellular degradation of aRBCs. Nine different plasma coagulation factors were evaluated and, with one explainable exception, all showed less than 20% change in their measured test versus control values, meeting the acceptance criteria. The relative temperature increase between test and control units never exceeded the 1.5 degrees C acceptance criterion for RBCs and 4 degrees C for plasma. CONCLUSION: Use of 13.56-MHz RFID technology is unlikely to have any significant temperature or biologic effects on aRBC and plasma units under normal operating conditions. PMID- 22313041 TI - The need for gynecologic follow-up among women veterans: the association of sexual assault and abnormal cervical cytology. PMID- 22313042 TI - Depressive symptoms in multiple sclerosis. PMID- 22313043 TI - Topological plasticity increases robustness of mutualistic networks. AB - 1. Earlier studies used static models to evaluate the responses of mutualistic networks to external perturbations. Two classes of dynamics can be distinguished in ecological networks; population dynamics, represented mainly by changes in species abundances, and topological dynamics, represented by changes in the architecture of the web. 2. In this study, we model the temporal evolution of three empirical plant-pollination networks incorporating both population and topological dynamics. We test the hypothesis that topological plasticity, realized through the ability of animals to rewire their connections after depletion of host abundances, enhances tolerance of mutualistic networks to species loss. We also compared the performance of various rewiring rules in affecting robustness. 3. The results show that topological plasticity markedly increased the robustness of mutualistic networks. Our analyses also revealed that network robustness reached maximum levels when animals with less host plant availability were more likely to rewire. Also, preferential attachment to richer host plants, that is, to plants exhibiting higher abundance and few exploiters, enhances robustness more than other rewiring alternatives. 4. Our results highlight the potential role of topological plasticity in the robustness of mutualistic networks to species extinctions and suggest some plausible mechanisms by which the decisions of foragers may shape the collective dynamics of plant pollinator systems. PMID- 22313044 TI - Type 2 diabetes mellitus in a patient with malignant insulinoma manifesting following surgery. AB - BACKGROUND: Insulinomas, although they are rare, are the most common of pancreatic islet cell tumours. The incidence is estimated at only four per million person-years and only 5-12% of reported cases are malignant. Distinction between malignant and benign tumours can only be made by the presence of metastasis, as there are no specific morphologic, biochemical or genetic features distinguishing them. Most patients with malignant insulinoma have lymph node or liver metastases and, rarely, bone involvement. The coincidence of insulinoma and diabetes mellitus is an extremely rare condition and reported only in a few cases. CASE REPORT: We report a 45-year-old woman who was diagnosed with insulinoma on the basis of clinical and laboratory findings and endoscopic examination. Histopathological diagnosis revealed well-differentiated endocrine carcinoma of the pancreas with lymph node metastases. The case was accepted as malignant insulinoma and the patient underwent surgery. Interestingly, hyperglycaemia occurred after the removal of the insulinoma, with the requirement for insulin in the post-operative 3 weeks, which was changed to oral anti diabetic agents as a permanent treatment. The patient is still being treated with oral anti-diabetic agents. We think that the patient might have had diabetes mellitus, because of insulin resistance that developed with a high-caloric intake stimulated by hypoglycaemia, and which had been masked for many years, but manifested overtly after removal of the tumour. CONCLUSIONS: Although this is a rare condition, clinicians should bear in mind that insulinomas may exist together with diabetes mellitus, and it is important to have this suspicion when considering the perioperative approach and for the prevention of morbidities. PMID- 22313045 TI - Multiplex quantitative fluorescent polymerase chain reaction for detection of aneuploidies. AB - Quantitative fluorescent polymerase chain reaction (QF-PCR) is a well-established method in Western countries where commercial kits are being used for rapid prenatal diagnosis of aneuploidies. The limitations of these kits are that these are basically designed for the Caucasian population and are very expensive. Thus there is an urgent need to investigate the informative markers in the Asian population and to develop indigenous informative markers for detection of aneuploidies. This is a cost-effective alternate to the commercial kits and can be easily used in developing countries. We have tested three STR markers (D21S1435, D21S11, and D21S1411) in confirmed cases of Down syndrome and their parents. Origin of nondisjunction was also determined by means of QF-PCR. All the Down syndrome cases were confirmed for trisomy 21 by STR analysis. The results matched 100% with the karyotyping results. Nondisjunction was maternal in 87.5% cases and paternal in 12.5% cases. Nondisjunction during meiosis I was responsible for 87.5% cases of maternal nondisjunction and 100% cases of paternal nondisjunction. The combination of three STR markers is highly informative and can be used for diagnosis of trisomy 21 in India. PMID- 22313046 TI - Endothelial nitric oxide synthase gene polymorphisms and the risk of diabetic nephropathy in type 2 diabetes mellitus. AB - Endothelial dysfunction plays an important role in the pathogenesis of diabetic vascular disease, including diabetic nephropathy (DN). Endothelial nitric oxide synthase (eNOS) gene polymorphisms that affect eNOS activity are associated with endothelial dysfunction. The aim of this study was to evaluate the association of three polymorphisms of the eNOS gene (894G>T, -786T>C, and 27-bp-VNTR) with the risk of DN among type 2 diabetic patients. A total of 400 type 2 diabetic patients were enrolled in this study. The DN group comprised 200 patients; the group of diabetics without nephropathy comprised another 200 patients. Genetic analysis for eNOS gene polymorphisms was done in all subjects. Measurement of nitric oxide levels was estimated. The C allele for -786T>C and the T allele for 894G>T were significantly more frequent in diabetics with nephropathy than in diabetics without nephropathy (p<0.001; odds ratio [OR] and 95% confidence interval [CI] for the C allele=1.64 [1.24-2.17] and p<0.001; OR and 95% CI=1.7 [1.27-2.26] for the T allele). The haplotypes CTa (with all the mutant alleles) and CTb were significantly more common in patients with DN (p=0.01 and 0.003, respectively). These results suggested that the eNOS polymorphisms might represent genetic determinants for developing DN in type 2 diabetic Egyptians. PMID- 22313047 TI - Genetic polymorphisms of CYP2C8 in the Czech Republic. AB - AIM: CYP2C8 represents 7% of the hepatic cytochrome system and metabolizes around 5% of drugs in phase I processes. It also plays a significant role in metabolism of endogenous compounds. More than 20 single-nucleotide polymorphisms (SNPs) have been noted, mainly in exons 3, 5, and 8. The most studied SNPs may lead to decreased enzyme activity and may have impact on drug metabolism. Variant alleles are called CYP2C8*2 (I269F), CYP2C8*3 (R139K, K399R), and CYP2C8*4(I264M). Our aim was to investigate the frequency of major functional SNPs among the Czech population. MATERIAL AND METHODS: DNA was isolated from whole blood of 161 healthy, young, and unrelated subjects (94 men and 67 women, aged from 23 to 28 years). The genotypes of polymorphic positions CYP2C8*2, CYP2C8*3 (G416A, A1196G), and CYP2C8*4 were determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS AND CONCLUSION: Observed allele frequencies were 10.9%, 5.9%, and 0.3% for the alleles CYP2C8*3, CYP2C8*4, and CYP2C8*2, respectively. Both CYP2C8*3 (G416A, A1196G) alleles have been found in complete linkage disequilibrium. The allele distribution complies well with Hardy-Weinberg equilibrium. Allele frequencies of functionally important CYP2C8 variants in the Czech population are similar to that of other Caucasian populations. PMID- 22313048 TI - Developing national guidance on genetic testing for breast cancer predisposition: the role of economic evidence? AB - Advancements in genetic testing to identify predisposition for hereditary breast cancer (HBC) mean that it is important to understand the incremental costs and benefits of the new technologies compared with current testing strategies. This study aimed to (1) identify and critically appraise existing economic evidence for BRCA1/2 mutation testing for HBC and (2) establish whether economic evidence was used to inform national guidance in England and Wales. A telephone interview with diagnostic laboratories (n=14) offering BRCA1/2 mutation testing identified that 9 (64%) used Sanger DNA sequencing with multiplex ligation-dependent probe amplification and two offered next generation sequencing. A systematic review identified 15 economic studies that evaluated: genetic testing for HBC (5 studies); preventive management options for women at risk of HBC (8 studies); and different laboratory approaches for BRCA1 testing (2 studies). These evaluations were not relevant to U.K. practice, and therefore the development of national guidance using a risk threshold to trigger BRCA1/2 testing has not been informed by existing economic evidence. The lack of economic evidence supporting the current risk threshold for national guidance has implications for the efficient use of healthcare resources and the design of economic evaluations of new technologies for BRCA1/2 testing. PMID- 22313049 TI - Locked on one side only: ground state dynamics of the outer membrane efflux duct TolC. AB - Playing a major role in the expulsion of antibiotics and the secretion of cell toxins in conjunction with inner membrane transporters of three protein superfamilies, the outer membrane channel TolC occurs in at least two states blocking or permitting the passage of substrates. The details of the underlying gating mechanism are not fully understood. Addressing the questions of extracellular access control and periplasmic gating mechanism, we conducted a series of independent, unbiased 150-300 ns molecular dynamics simulations of wild type TolC in a phospholipid membrane/150 mM NaCl water environment. We find that TolC opens and closes freely on the extracellular side, suggesting the absence of a gating mechanism on this side in the isolated protein. On the periplasmic side, we observe the outer periplasmic bottleneck region adopting in all simulations a conformation more open than the TolC wild-type crystal structures until in one run the successive binding of two sodium ions induces the transition to a conformation more closed than any of the available TolC X-ray structures. Concurrent with a heightened sodium residence probability near Asp374, the inner periplasmic bottleneck region at Asp374 remains closed throughout the simulations unless all NaCl is removed from the system, inducing a reopening of the outer and inner bottleneck. Our findings suggest that TolC is locked only on the periplasmic side in a sodium-dependent manner. PMID- 22313050 TI - Sequence-specific biosensors report drug-induced changes in epigenetic silencing in living cells. AB - Treatment with demethylating drugs can induce demethylation and reactivation of abnormally silenced tumor suppressor genes in cancer cells, but it can also induce potentially deleterious loss of methylation of repetitive elements. To enable the observation of unwanted drug effects related to loss of methylation of repetitive DNA, we have developed a novel biosensor capable of reporting changes in DNA accessibility via luminescence, in living cells. The biosensor design comprises two independent modules, each with a polydactyl zinc finger domain fused to a half intein and to a split-luciferase domain that can be joined by conditional protein splicing after binding to adjacent DNA targets. We show that an artificial zinc finger design specifically targeting DNA sequences near the promoter region of the L1PA2 subfamily of Line-1 retroelements is able to generate luminescent signals, reporting loss of epigenetic silencing and increased DNA accessibility of retroelements in human cells treated with the demethylating drugs decitabine or 5-azacytidine. PMID- 22313051 TI - Regulation of lipid metabolism by Dicer revealed through SILAC mice. AB - Dicer is a ribonuclease whose major role is to generate mature microRNAs, although additional functions have been proposed. Deletion of Dicer leads to embryonic lethality in mice. To study the role of Dicer in adults, we generated mice in which administration of tamoxifen induces deletion of Dicer. Surprisingly, disruption of Dicer in adult mice induced lipid accumulation in the small intestine. To dissect the underlying mechanisms, we carried out miRNA, mRNA, and proteomic profiling of the small intestine. The proteomic analysis was done using mice metabolically labeled with heavy lysine (SILAC mice) for an in vivo readout. We identified 646 proteins, of which 80 were up-regulated >2-fold and 75 were down-regulated. Consistent with the accumulation of lipids, Dicer disruption caused a marked decrease of microsomal triglyceride transfer protein, long-chain fatty acyl-CoA ligase 5, fatty acid binding protein, and very-long chain fatty acyl-CoA dehydrogenase, among others. We validated these results using multiple reaction monitoring (MRM) experiments by targeting proteotypic peptides. Our data reveal a previously unappreciated role of Dicer in lipid metabolism. These studies demonstrate that a systems biology approach by integrating mouse models, metabolic labeling, gene expression profiling, and quantitative proteomics can be a powerful tool for understanding complex biological systems. PMID- 22313052 TI - Political violence and child adjustment: longitudinal tests of sectarian antisocial behavior, family conflict, and insecurity as explanatory pathways. AB - Understanding the impact of political violence on child maladjustment is a matter of international concern. Recent research has advanced a social ecological explanation for relations between political violence and child adjustment. However, conclusions are qualified by the lack of longitudinal tests. Toward examining pathways longitudinally, mothers and their adolescents (M = 12.33, SD = 1.78, at Time 1) from 2-parent families in Catholic and Protestant working class neighborhoods in Belfast, Northern Ireland, completed measures assessing multiple levels of a social ecological model. Utilizing autoregressive controls, a 3-wave longitudinal model test (T1, n = 299; T2, n = 248; T3, n = 197) supported a specific pathway linking sectarian community violence, family conflict, children's insecurity about family relationships, and adjustment problems. PMID- 22313053 TI - Antiviral properties of polymeric aziridine- and biguanide-modified core-shell magnetic nanoparticles. AB - Polycationic superparamagnetic nanoparticles (~150-250 nm) were evaluated as virucidal agents. The particles possess a core-shell structure, with cores consisting of magnetite clusters and shells of functional silica covalently bound to poly(hexamethylene biguanide) (PHMBG), polyethyleneimine (PEI), or PEI terminated with aziridine moieties. Aziridine was conjugated to the PEI shell through cationic ring-opening polymerization. The nanometric core-shell particles functionalized with biguanide or aziridine moieties are able to bind and inactivate bacteriophage MS2, herpes simplex virus HSV-1, nonenveloped infectious pancreatic necrosis virus (IPNV), and enveloped viral hemorrhagic septicaemia virus (VHSV). The virus-particle complexes can be efficiently removed from the aqueous milieu by simple magnetocollection. PMID- 22313054 TI - Diet and risk of coronary heart disease. PMID- 22313055 TI - Development and validation of a spectrophotometric method for quantification of total glucosinolates in cruciferous vegetables. AB - Given their putative role in chemoprevention, validated methods are needed for quantification of total glucosinolates. Based on the colorimetric reaction of ferricyanide with 1-thioglucose, released by alkaline hydrolysis of glucosinolates, we developed a simple and sensitive method for spectrophotometric quantification of total glucosinolates in cruciferous vegetables. Lyophilized and ground vegetables are extracted with 80% boiling methanol. Extracted glucosinolates are isolated using a strong anion exchange column and then hydrolyzed with 2 N NaOH to release 1-thioglucose. Ferricyanide is added, and the decrease in absorbance is measured at 420 nm, with final values adjusted for background. Recovery of internal standard (sinigrin) was 107%. Intra- and interassay coefficients of variation were 5.4% and 15.8%, respectively. Dose response was linear with sinigrin and amount of plant material extracted (R(2) >= 0.99). Using sinigrin, the lower limit of quantification was 0.6 mg. This straightforward method may be an alternative to time-consuming and costly chromatographic methods. PMID- 22313056 TI - Selection of antibiotics for meticillin-resistant Staphylococcus pseudintermedius: time to revisit some old drugs? AB - The aim of this review is to consider systemic therapy options for meticillin resistant Staphylococcus pseudintermedius (MRSP). Infections caused by MRSP in small animals--particularly dogs--have been frustrating veterinarians in recent years. After a susceptibility test is performed, veterinarians are left to select from drugs that have not been frequently encountered on a susceptibility report. Some of these are old drugs that have not been used regularly by veterinary dermatologists. As MRSP is, by definition, resistant to all beta-lactam antibiotics, including cephalosporins, penicillins and amoxicillin-clavulanate combinations, the beta-lactam drugs are not an option for systemic treatment. As most MRSPs are multidrug resistant, familiar drugs, such as trimethoprim sulfonamides, fluoroquinolones, macrolides and lincosamides (clindamycin), are also not usually an option for treatment. Therefore, veterinarians are left with drugs such as rifampicin, chloramphenicol, tetracyclines, aminoglycosides and vancomycin to choose from on the basis of an in vitro susceptibility test. Some of these drugs were originally approved over 50 years ago and may not be familiar to some veterinarians. Each of these drugs possesses unique properties and has particular advantages and disadvantages. Veterinarians should be particularly aware of the adverse effects, limitations and precautions when using these drugs. New drugs also have been developed for meticillin-resistant Staphylococcus aureus in humans. These include linezolid, ceftaroline, daptomycin and tigecycline. Although these drugs are very infrequently--if ever--considered for veterinary use, the properties of these drugs should also be known to veterinary dermatologists. PMID- 22313057 TI - HPLC assay and pharmacokinetics and tissue distribution study of glycyrrhetinic acid liposomes modified with galactosylated lipid. AB - The aim of this study was to evaluate the pharmacokinetics and tissue distribution of the glycyrrhetinic acid (GA) liposome modified with galactosylated lipid (NOH-GA-LP), compared with GA conventional liposome (GA-LP) and GA solution in mice. The pharmacokinetics and biodistribution of liposomal and solution formulation of GA in mice were studied after intravenous administration. Plasma and tissues were treated using liquid-liquid extraction and determined using reversed-phase high-performance liquid chromatography. Results showed that the mean residence times of NOH-GA-LP (2.99-fold) and GA-LP (2.94-fold) were higher than that of the GA solution in plasma. NOH-GA-LP produced a drug concentration in the liver that was markedly higher than that in other tissues and was approximately 2.0- and 4.8-fold of that of GA-LP and GA solution, respectively. In conclusion, the NOH-GA-LP prepared in this study is a promising sustained-release and drug-targeting system for antitumor drugs. PMID- 22313058 TI - The early history of ventilation. PMID- 22313059 TI - Intra-abdominal hypertension and abdominal compartment syndrome - making progress? PMID- 22313060 TI - Risks of anaesthesia and surgery in elderly patients. PMID- 22313061 TI - Benefits and risks of using gelatin solution as a plasma expander for perioperative and critically ill patients: a meta-analysis. AB - This meta-analysis aimed to evaluate the benefits and risks of gelatin solutions compared to other intravenous fluids for patients in perioperative and critical care settings. Of the 66 studies identified from MEDLINE and EMBASE databases, 30 randomised controlled trials involving 2709 patients met the inclusion criteria and were subject to meta-analysis. The risk of mortality (odds ratio 1.03, 95% confidence interval 0.80 to 1.32) and amount of blood loss (weighted-mean difference 7.56 ml, 95% confidence interval 18.75 to 33.87) were not significantly different between patients who were treated with gelatin solutions and other types of intravenous fluids. When compared to starches, gelatin solutions were associated with a lower risk of acute renal failure (odds ratio 0.43, 95% confidence interval 0.20 to 0.92; P=0.03). When gelatin solutions were compared to isotonic albumin, patients who were treated with gelatin solutions required a small, but significantly greater amount of blood transfusion (weighted mean-difference 180 ml, 95% confidence interval 8.1 to 353.6; P=0.04). These findings suggest that using gelatin solutions is associated with a lower risk of acute renal failure compared to older starches. Using gelatin as a plasma expander appears to have no significant advantages over crystalloids or isotonic albumin on mortality and may have a slightly higher risk of requiring allogeneic blood transfusion in perioperative and critically ill patients. An adequately powered randomised controlled trial with economic analysis is needed before gelatin solution can be recommended as a routine plasma expander for patients undergoing major surgery or who are critically ill. PMID- 22313062 TI - The role of regional anaesthesia techniques in the management of acute pain. AB - Regional anaesthesia and analgesia techniques are used to effectively manage acute pain after a variety of surgeries. With the rapid growth of ultrasound guided procedures, anaesthetists are re-examining regional anaesthesia and analgesia and their roles in pain management. In this evolving field previous published data may not reflect current practice. Therefore, a narrative review of recent literature was undertaken to establish the current utility and efficacy of regional anaesthesia and analgesia for the management of acute pain following surgery. Only prospective randomised controlled trials published between March 2009 and March 2011 with outcome measures of analgesia efficacy were included. Sixty-five randomised controlled trials were identified involving 4841 patients. Regional techniques for the management of knee (26%), abdominal (26%) and shoulder (14%) surgery were most frequently studied. The review provides further evidence that regional anaesthesia and analgesia can offer excellent analgesia with acceptable side-effects for the management of postsurgical pain. In addition, the results of this review support the use of ultrasound guidance when performing regional techniques and continuous catheter techniques to prolong analgesia. PMID- 22313063 TI - The mitochondrial permeability transition pore and its role in anaesthesia triggered cellular protection during ischaemia-reperfusion injury. AB - This review summarises the most recent data in support of the role of the mitochondrial permeability transition pore (mPTP) in ischaemia-reperfusion injury, how anaesthetic agents interact with this molecular channel, and the relevance this holds for current anaesthetic practice. Ischaemia results in damage to the electron transport chain of enzymes and sets into play the assembly of a non-specific mega-channel (the mPTP) that transgresses the inner mitochondrial membrane. During reperfusion, uncontrolled opening of the mPTP causes widespread depolarisation of the inner mitochondrial membrane, hydrolysis of ATP, mitochondrial rupture and eventual necrotic cell death. Similarly, transient opening of the mPTP during less substantial ischaemia leads to differential swelling of the intermembrane space compared to the mitochondrial matrix, rupture of the outer mitochondrial membrane and release of pro-apoptotic factors into the cytosol. Recent data suggests that cellular protection from volatile anaesthetic agents follows specific downstream interactions with this molecular channel that are initiated early during anaesthesia. Intravenous anaesthetic agents also prevent the opening of the mPTP during reperfusion. Although by dissimilar mechanisms, both volatiles and propofol promote cell survival by preventing uncontrolled opening of the mPTP after ischaemia. It is now considered that anaesthetic-induced closure of the mPTP is the underlying effector mechanism that is responsible for the cytoprotection previously demonstrated in clinical studies investigating anaesthetic-mediated cardiac and neuroprotection. Manipulation of mPTP function offers a novel means of preventing ischaemic cell injury. Anaesthetic agents occupy a unique niche in the pharmacological armamentarium available for use in preventing cell death following ischaemia-reperfusion injury. PMID- 22313064 TI - Laptops and smartphones in the operating theatre - how does our knowledge of vigilance, multi-tasking and anaesthetist performance help us in our approach to this new distraction? AB - There has been no research performed concerning the effects of the use of laptops and smartphones in the operating theatre on anaesthetist performance, yet these devices are now in frequent use. This article explores the implications of this phenomenon. The cognitive and environmental factors that support or detract from vigilance and multi-tasking are explored and core anaesthetic literature on the nature of anaesthetic work and operating theatre distractions is reviewed. Experienced anaesthetists are skilled at multi-tasking while maintaining situational awareness, but there are limits. Noise, interruptions and emotional arousal are detrimental to the cognitive performance of anaesthetists. While limited reading during periods of low task load may not reduce vigilance, computer use introduces text-based activities that are more interactive and potentially more distracting. All anaesthetists need to be mindful of the limits to the human attention span which requires observation and limiting distractions. Trainees have less experience and less 'attentional' safety margin, so should avoid adding additional distractions such as discretionary use of laptops or smartphones to their operating theatre work. We provide recommendations for future research on the specific advantages and disadvantages of pervasive computing in the operative theatre. PMID- 22313065 TI - Incidence, risk factors and outcome associations of intra-abdominal hypertension in critically ill patients. AB - Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are significantly associated with morbidity and mortality. We performed a prospective observational study and applied recently published consensus criteria to measure and describe the incidence of IAH and ACS, identify risk factors for their development and define their association with outcomes. We studied 100 consecutive patients admitted to our general intensive care unit. We recorded relevant demographic, clinical data and maximal (max) and mean intra-abdominal pressure (IAP). We measured and defined IAH and ACS using consensus guidelines. Of our study patients, 42% (by IAPmax) and 38% (by IAPmean) had IAH. Patients with IAH had greater mean body mass index (30.4 +/- 9.6 vs 25.4 +/- 5.6 kg/m(2), P=0.005), Acute Physiology and Chronic Health Evaluation III score (78.2 +/- 28.5 vs 65.5 +/- 29.2, P=0.03) and central venous pressure (12.8 +/- 4.8 vs 9.2 +/- 3.5 mmHg, P <0.001), lower abdominal perfusion pressure (67.6+/-13.5 vs 79.3 +/- 17.3 mmHg, P <0.001) and lower filtration gradient (51.2 +/- 14.8 vs 71.6 +/- 17.7 mmHg; P <0.001). Risk factors associated with IAH were body mass index =30 (P <0.001), higher central venous pressure (P <0.001), presence of abdominal infection (P=0.005) and presence of sepsis on admission (P=0.035). Abdominal compartment syndrome developed in 4% of patients. IAP was not associated with an increased risk of mortality after adjusting for other confounders. We conclude that, in a general population of critically ill patients, using consensus guidelines, IAH was common and significantly associated with obesity and sepsis on admission. In a minority of patients, IAH was associated with abdominal compartment syndrome. In this cohort IAH was not associated with an increased risk of mortality. PMID- 22313066 TI - Emergency surgery in the elderly: a retrospective observational study. AB - We conducted a retrospective observational study in a regional hospital on patients aged 80 years or over undergoing emergency procedures. We included 202 emergency procedures performed on 178 patients over 185 separate admissions. The aim was to obtain a 'snapshot' of the risks of emergency surgery in the elderly and to analyse functional status both as a risk factor and as an outcome in this patient group. The most common complications were infective (21% of patients), cardiovascular (18%) and neurological (18%). Overall mortality was 9%. Increasing age, higher American Society of Anesthesiologists physical status score and poorer pre-admission functional status appeared to be associated with increased complications and mortality. Although two-thirds of both functionally independent and partially dependent patients were discharged at their original level of function, 28% of partially dependent patients required discharge to a high-level care nursing home, whereas only 5% of the initially independent patients had this poor outcome. Improvement in our ability to stratify risk in this enlarging patient group should help improve our clinical decision-making, which may have benefits both for patients and resource allocation. PMID- 22313067 TI - Plasma free cortisol and B-type natriuretic peptide in septic shock. AB - Previous studies of patients with septic shock have independently demonstrated alterations in plasma concentrations of B-type natriuretic peptide and plasma free cortisol. Previous data suggest that a reciprocal relationship might exist. However, the relationship between these hormones in patients with septic shock is unclear. We sought to compare paired measurement of both B-type natriuretic peptide and plasma free cortisol in a study of septic shock patients. Twenty-one consecutive adult patients from a tertiary level, multidisciplinary intensive care unit underwent blood collection within 72 hours of developing septic shock. Mean +/- SD Acute Physiology and Chronic Health Evaluation III score was 80.1 +/- 23.8. Hospital mortality was 29%. Log plasma free cortisol demonstrated positive correlation with log B-type natriuretic peptide (r=0.55, P=0.019). Log plasma free cortisol also correlated with Acute Physiology and Chronic Health Evaluation III score (r=0.67, P <0.001) and noradrenaline dose (r=0.55, P=0.01). Acute Physiology and Chronic Health Evaluation III (P=0.001) and noradrenaline dose (P=0.02) were independent predictors of plasma free cortisol. A model incorporating both variables explained 68% of variation in plasma free cortisol (R-square=0.682). This study of patients with septic shock demonstrates a previously unappreciated positive correlation between plasma free cortisol and b type natriuretic peptide concentration. Acute Physiology and Chronic Health Evaluation III score and noradrenaline dose were independent predictors of plasma free cortisol. PMID- 22313068 TI - L-arginine cardioplegia reduces oxidative stress and preserves diastolic function in patients with low ejection fraction undergoing coronary artery surgery. AB - PL-arginine cardioplegia decreases biochemical markers of myocardial damage and oxidative stress in patients with normal left ventricular function. We investigated the effects of L-arginine supplemented cardioplegic arrest in patients with reduced ejection fraction. Fifty-three adult patients with left ventricular ejection fraction <35% undergoing elective coronary artery bypass surgery were randomised to receive blood cardioplegia with or without L-arginine. Following cardiopulmonary bypass, measured endpoints were cardiac troponin-I concentration at 12 and 24 hours, coronary sinus concentrations of malondialdehyde and superoxide dismutase activity at five and 15 minutes, lactic acid flux at one, five and 15 minutes and left ventricular systolic and diastolic function after protamine administration. There were no differences in cardiac troponin-I between groups. Malondialdehyde was lower in the L-arginine group, 0.28 +/- 0.12 vs 0.48 +/- 0.32 (5 minutes) and 0.31 +/- 0.14 vs 0.38 +/- 0.15 nmol.ml(-1) (15 minutes) (P=0.0004). Superoxide dismutase activity was higher in L-arginine group, 229 +/- 87 vs 191.3 +/- 68 (5 minutes), 229 +/- 54 vs 198 +/- 15 nmol.minute(-1).m(l) (15 minutes) (P=0.005). Lactic acid flux was lower in L arginine group, 0.15 +/- 0.23 vs 0.48 +/- 0.32 (1 minute), 0.08 +/- 0.19 vs 0.38 +/- 0.31 (5 minutes) and -0.15 +/- 0.13 vs 0.26 +/- 0.30 mmol.l(-1) (15 minutes), (P=0.0003). There was no difference in left ventricular systolic function. The mitral annular tissue Doppler inflow (e') velocity during early diastole improved in the L-arginine group following cardiopulmonary bypass (control 4.2 +/- 1.9 cm.s(-1) to 3.6 +/- 1.2 cm.s(-1) vs L-arginine 3.8 +/-1.2 cm.s(-1) to 4.6 +/- 1.4 cm.s(-1)) (P=0.018). In patients with reduced ejection fraction, L-arginine supplemented cardioplegic arrest did not affect postoperative cardiac troponin-I levels, but attenuated cardiac cellular peroxidation and improved early left ventricular diastolic function. PMID- 22313069 TI - Blood loss and replacement for paediatric cranioplasty in Australia - a prospective national audit. AB - We prospectively audited blood loss and blood replacement in every child less than 24 months of age undergoing cranioplasty for craniosynostosis in Australia during 2008, in order to obtain more accurate data for the discussion of perioperative transfusion risk. A total of 127 cases were performed at seven centres. There were no directed or autologous blood donations. No patient received preoperative erythropoietin. A total of 233 units of homologous red blood cells were transfused. Overall, 83% of patients received a blood transfusion. This included 100% of patients undergoing cranial vault reconstruction (CVR) and 98% of patients undergoing fronto-orbital advancement (FOA), but only 32% of spring cranioplasty patients. Exposure to no more than one donor was achieved in 60% of FOA patients and 36% of CVR patients. Estimated blood volume loss was more than one blood volume in 36% of CVR and 36% of FOA, but only 12% of spring cranioplasty, and more than two blood volumes in 4% of CVR and 11% of FOA. Differences in surgical technique and volume of surgery between different centres appeared to affect transfusion rates. Children with recognised craniofacial syndromes and those undergoing repeat surgery appeared to have greater blood loss and blood product exposure. There were two cases of sudden massive haemorrhage secondary to dural venous sinus tear, but no death or perioperative cardiac arrest. These findings indicate that blood loss requiring blood product replacement is common in patients <24 months of age undergoing cranioplasty for craniosynostosis, particularly in patients undergoing FOA and CVR. PMID- 22313070 TI - Comparison of haemodynamic responses following different concentrations of adrenaline with and without lignocaine for surgical field infiltration during cleft lip and cleft palate surgery in children. AB - Surgical field infiltration with adrenaline is common practice for quality surgical field during cleft lip and palate repair in children. Intravascular absorption of adrenaline infiltration often leads to adverse haemodynamic responses. In this prospective, double-blinded, randomised study the haemodynamic effects, quality of surgical field and postoperative analgesia following surgical field infiltration with different concentrations of adrenaline with and without lignocaine were compared in 100 American Society of Anesthesiologists physical status I children aged six months to seven years undergoing cleft lip/palate surgery. A standard anaesthesia protocol was used and they were randomised into four groups based on solution for infiltration: adrenaline 1:400,000 (group A), adrenaline 1:200,000 (group B), lignocaine + adrenaline 1:400,000 (group C) and lignocaine + adrenaline 1:200,000 (group D). Statistically significant tachycardia and hypertension occurred only in group B as compared to other groups (P <0.001). The peak changes in heart rate and mean arterial pressure following infiltration occurred at 4.3 +/- 2.4, 3.8 +/- 1.5, 5.7 +/- 3.2 and 5.9 +/- 4.9 minutes in groups A, B, C and D respectively. Surgical field was comparable among all groups. Postoperative pain scores and rescue analgesic requirements were lesser in the groups where lignocaine was added to the infiltrating solution (P <0.05). We found that 1:400000 or 1:200000 adrenaline with lignocaine 0.5 to 0.7% is most suitable for infiltration in terms of stable haemodynamics, quality of surgical field and good postoperative analgesia in children. PMID- 22313071 TI - Incidence of difficult intubation in intensive care patients: analysis of contributing factors. AB - Difficulties in endotracheal intubation increase morbidity and mortality in intensive care patients. We studied the problem in surgical intensive care patients with the aim of risk reduction. Patients intubated in the intensive care unit were evaluated. The intubations were performed or supervised by anaesthetists following the algorithm valid at the time of the study. Fifty percent of the 198 intubations were performed by specialist anaesthetists, 41.5% by anaesthesia trainees and 8.5% by surgical trainees. The initial attempt was by direct laryngoscopy (n=173), flexible fibrescope (n=8) or blind nasal technique (n=17). When direct laryngoscopy failed (n=7), intubation was accomplished with an intubating laryngeal mask airway (n=5), Frova stylet (n=1) or fibrescope (n=1). Thirty percent were rated as easy, 47% as moderately easy and 23% as difficult. Difficult intubations were associated with a higher incidence of anatomic anomalies, difficult bag-mask ventilation and severe oxygen desaturation. Every intubation in the ICU setting should be considered potentially difficult. The existing algorithm should be modified to incorporate the American Society of Anesthesiologists difficult airway algorithm adapted to the needs of the intensive care unit. A training program for alternative methods of airway management for difficult intubations should be established. PMID- 22313072 TI - Improving the C-MAC video laryngoscopic view when applying cricoid pressure by allowing access of assistant to the video screen. AB - Cricoid pressure, as part of rapid sequence induction, may on occasion worsen laryngoscopic views and intubating conditions. We investigated whether allowing the assistant applying cricoid pressure to view the video laryngoscope screen would improve the laryngoscopic views compared to when they were blinded to the video screen. Laryngoscopy using the C-MAC video laryngoscope was performed in 51 patients undergoing elective general anaesthesia. Photographs were recorded sequentially under the following conditions: A) cricoid pressure by an assistant unable to see the video monitor, and B) cricoid pressure optimised by an assistant able to see the video monitor. These photographs were analysed offline by assessors blinded to whether the photo was obtained with blinded or non blinded cricoid pressure application. Subjectively, 41% of views were improved when the assistant applying cricoid pressure was able to see the C-MAC screen, compared to those unable to see the screen. The view was unchanged in 45%, but initially worsened in 14%. These findings suggest that assistants applying cricoid pressure when a C-MAC is used should have access to the video image, but must also respond to requests for change from the person performing the intubation. PMID- 22313073 TI - A useful new coma scale in acute stroke patients: FOUR score. AB - Assessment of the severity of unconsciousness in patients with impaired consciousness, prediction of mortality and prognosis are currently the most studied subjects in intensive care. The aim of this study was to investigate the usefulness of the Full Outline of UnResponsiveness (FOUR) score in intensive care unit patients with stroke and the associations of FOUR score with the clinical outcome and with other coma scales (Glasgow [GCS] and Acute Physiology and Chronic Health Evaluation II). One hundred acute stroke patients (44 male, 56 female), who were followed in a neurology intensive care unit, were included in this prospective study. The mean age of the patients was 70.49 +/- 12.42 years. Lesion types were determined as haemorrhagic in 30 and ischaemic in 70 patients. FOUR scores on the day of admission and the first, third and 10th days of patients who died within 15 days were lower when compared to scores of patients who survived (P=0.005, P=0.000, P=0.000 and P=0.000 respectively). Receiver operating characteristic curve analysis showed significant trending with both FOUR score and GCS for prognosis; the area under curve ranged from 0.675 (95% confidence interval 0.565 to 0.786) when measurements had been made on day 3 to 0.922 (95% confidence interval 0.867 to 0.977) and 0.981 (95% confidence interval 0.947 to 1.015) for day 10. We suggest that FOUR score is a useful scale for evaluation of acute stroke patients in the intensive care unit as a homogeneous group, with respect to the outcome estimation. PMID- 22313074 TI - End-of-life practices in a tertiary intensive care unit in Saudi Arabia. AB - Our aim was to evaluate end-of-life practices in a tertiary intensive care unit in Saudi Arabia. A prospective observational study was conducted in the medical surgical intensive care unit of a teaching hospital in Riyadh, Saudi Arabia. Over the course of the one-year study period, 176 patients died and 77% of these deaths were preceded by end-of-life decisions. Of these, 66% made do-not resuscitate decisions, 30% decided to withhold life support and 4% withdrew life support. These decisions were made after a median time of four days (Q1 to Q3: 1 to 9) and at least one day before death (Q1 to Q3: 1 to 4). The patients' families or surrogates were informed for 88% of the decisions and all decisions were documented in the patients' medical records. Despite religious and cultural values, more than three-quarters of the patients whose deaths were preceded by end-of-life decisions gave do-not-resuscitate decisions before death. These decisions should be made early in the patients' stay in the intensive care unit. PMID- 22313075 TI - Ventilator versus manual hyperinflation in clearing sputum in ventilated intensive care unit patients. AB - The aim of hyperinflation in the ventilated intensive care unit patient is to increase oxygenation, reverse lung collapse and clear sputum. The efficacy and consistency of manual hyperventilation is well supported in the literature, but there is limited published evidence supporting hyperventilation utilising a ventilator. Despite this, a recent survey established that almost 40% of Australian tertiary intensive care units utilise ventilator hyperinflation. The aim of this non-inferiority cross-over study was to determine whether ventilator hyperinflation was as effective as manual hyperinflation in clearing sputum from patients receiving mechanical ventilation using a prescriptive ventilator hyperinflation protocol. Forty-six patients received two randomly ordered physiotherapy treatments on the same day by the same physiotherapist. The efficacy of the hyperinflation modes was measured by sputum wet weight. Secondary measures included compliance, tidal volume, airway pressure and PaO2/FiO2 ratio. There was no difference in wet weight of sputum cleared using ventilator hyperinflation or manual hyperinflation (mean 3.2 g, P=0.989). Further, no difference in compliance (P=0.823), tidal volume (P=0.219), heart rate (P=0.579), respiratory rate (P=0.929) or mean arterial pressure (P=0.593) was detected. A statistically significant difference was seen in mean airway pressure (P=0.002) between techniques. The effect of techniques on the PaO2/FiO2 response ratio was dependent on time (interaction P=0.024). Physiotherapy using ventilator hyperinflation cleared a comparable amount of sputum and was as safe as manual hyperinflation. This research describes a ventilator hyperinflation protocol that will serve as a platform for continued discussion, research and development of its application in ventilated patients. PMID- 22313076 TI - Premedication with granisetron reduces shivering during spinal anaesthesia in children. AB - This study evaluates the effect of prophylactic granisetron on the incidence of postoperative shivering after spinal anaesthesia in children. Eighty children, American Society of Anesthesiologists physical status I to II and aged two to five years were scheduled for surgery of the lower limb under spinal anaesthesia. The children were randomised to receive 10 ug/kg granisetron diluted in 10 ml saline 0.9% intravenously (group 1, n=40) or placebo (10 ml 0.9% saline, group 2, n=40) to be given over five minutes just before spinal puncture. Shivering, core temperature and the levels of motor and sensory block were assessed. No patients shivered in group 1. However, six patients shivered in Group 2 (P=0.025). There were no significant differences in the other measured variables between the groups. Granisetron is an effective agent to prevent shivering after spinal anaesthesia in children from two to five years of age. PMID- 22313077 TI - A new technique for post-pyloric feeding tube placement by palpation in lean critically ill patients. AB - Various techniques have been described for blind bedside placement of a post pyloric feeding tube. However, there is no universal method and the technique depends on the local institutional resources and expertise. The purpose of this study was to evaluate a simple new technique for the bedside placement of a post pyloric feeding tube in an intensive care unit using palpation to confirm tube position. We studied 47 consecutive ventilated patients (mean body mass index 22.4 +/- 4.2 kg/m(2)) requiring enteral tube feeding for nutritional support. We monitored the maximum intensity point of injected air 'bubbling' by palpation and estimated tube position. We monitored the movement of the maximum intensity point from the left upper quadrant to the right upper quadrant. If the maximum intensity point on the right upper quadrant diminished or weakened, we considered the tube had proceeded beyond the pylorus. By palpation, we could feel the bubbling of the injected air in all patients, but four patients were excluded because of failure to complete the protocol. The overall success rate including the four excluded cases was 85.1% (40/47) on the first attempt and 91.5% (43/47) when we included the second attempt. The median time for 40 successful tube placements on the first attempt was 10 (7 to 23) minutes. Our new palpation technique can successfully detect the position of a feeding tube in the stomach and help guide the tube to the correct location in the post-pyloric portion of the stomach in lean critically ill patients. PMID- 22313078 TI - Determinants of family satisfaction in the intensive care unit. AB - The aim of this study was to explore the degree and determinants of satisfaction of family members of patients being cared for in an Australasian intensive care unit. This was a prospective observational study that took place within a mixed medical/surgical, level three intensive care unit. One hundred and eight family members of patients staying in the intensive care for more than 48 hours were identified. Eight were excluded because next of kin contact details were unavailable. A questionnaire was posted to next of kin four weeks after intensive care unit discharge. Subjects who had not responded after four weeks were contacted by telephone and, if consent was given, a phone questionnaire was performed. Evidence of family meetings with the social worker or medical staff was sought in the patients' case notes retrospectively. Family satisfaction was measured using a 10-item questionnaire incorporating visual analogue scales. Seven subjects refused to participate. Fifty-nine responded by post and a further 25 agreed to a phone interview. Nine subjects were unable to be contacted. Eighty four family members were included, 73 of patients who survived. Overall family satisfaction was a high 8.0 (interquartile range 6.5 to 9.5). Highest scores recorded were for communications with nursing staff (9.0), while lowest scores were for frequency of doctors' communication (7.0). Families who had meetings with the social worker or medical staff were less likely to report dissatisfaction (relative risk 0.14; confidence interval 0.03 to 0.59; P=0.08; relative risk 0.23; confidence interval 0.07 to 0.81; P=0.02). Our study found that the majority of families are happy with their care in the intensive care unit. Social work and medical meetings with the family reduce dissatisfaction. PMID- 22313079 TI - Postoperative plasma paracetamol levels following oral or intravenous paracetamol administration: a double-blind randomised controlled trial. AB - In day-case surgery paracetamol is commonly given orally preoperatively, or intravenously intraoperatively. In this double-blind randomised controlled trial we investigated which of these methods of administration achieved therapeutic plasma levels most effectively in the early postoperative period. Thirty patients undergoing day case arthroscopy of the knee were randomised to receive either 1.0 g oral paracetamol 30 to 60 minutes preoperatively (20 patients) or 1.0 g intravenous paracetamol intraoperatively (10 patients). Plasma paracetamol levels were measured 30 minutes after arrival in the recovery room. Secondary outcomes included postoperative pain scores, rescue analgesia requirements and duration of stay in the recovery room. All patients receiving the intravenous preparation had plasma levels above the analgesic level compared to less than half (7/20) in the oral group. Mean plasma paracetamol levels were 88.6 umol/l for the intravenous group and 53.2 umol/l for the oral group (P=0.0005). There were trends towards reduced rescue analgesia and duration of stay in the recovery room for the intravenous group although not reaching statistical significance. There was no difference in pain scores between groups. Intraoperative administration of 1.0 g of intravenous paracetamol more reliably achieved effective paracetamol levels in the early postoperative period compared to an equal dose given orally preoperatively. Only a minority of patients receiving the 1.0 g oral dose preoperatively had plasma levels in the therapeutic analgesic range. PMID- 22313080 TI - Audit of extrapleural local anaesthetic infusion in neonates following repair of tracheo-oesophageal fistulae and oesophageal atresia via thoracotomy. AB - In order to reduce postoperative opioid requirement, extrapleural local anaesthetic infusion dosing recommendations and guidelines for extrapleural catheter insertion were developed in our institution for 'extubatable' neonates requiring short-gap neonatal tracheo-oesophageal fistula/oesophageal atresia repair (via thoracotomy) and audited prospectively. Data audited included patient characteristics, analgesia details and ventilation duration. We divided patients into two groups: group 1 - term patients (=36 weeks gestational age) with birth weights =2.5 kg; group 2 - pre-term patients (<36 weeks gestational age), with birth weights <2.5 kg and those with co-morbidities. There were 26 neonates in group 1 and 11 in group 2. All received extrapleural infusions of bupivacaine or levobupivacaine: the majority (90%) =300 ug.kg(-1).hour(-1) (median duration 43 hours, range 1.5 to 72 hours); 36% required morphine infusion and 39% were ventilated (median duration 34 hours, range 3 to 140 hours). In group 1, 24% required morphine infusion compared with 64% in group 2. Most group 1 patients (77%) were extubated immediately postoperatively; 20% had short duration ventilation (median 15 hours, range 11 to 37 hours); one required longer-term ventilation (231 hours). 82% of group 2 were ventilated for a median of 72 hours (range 3 to 140 hours). Review of patients' co-morbidities facilitated guideline revision. These now specify use in neonates requiring short-gap tracheo oesophageal fistula/oesophageal atresia repair who are term at =36 weeks gestational age and =2.5 kg birth-weight, anticipated as ready for extubation either immediately or shortly after surgery. PMID- 22313082 TI - Correction: adherent transversus abdominis plane catheter. PMID- 22313084 TI - Target controlled infusion pump failure due to worn drive nut. PMID- 22313085 TI - Three strikes and you're out: unanticipated hyperkalaemic cardiac arrest following rapid sequence intubation. PMID- 22313087 TI - A heads up for ultrasound. PMID- 22313086 TI - Modification of Diamedica drawover anaesthetic equipment to facilitate introduction to an Australian teaching hospital. PMID- 22313088 TI - The use of a 1 ml syringe tube as an open reservoir during arterial cannulation. PMID- 22313089 TI - Acute renal failure and liver necrosis associated to allopurinol therapy. PMID- 22313090 TI - Understanding the diversity of male clients of sex workers in China and the implications for HIV prevention programmes. AB - Male clients of sex workers have been overlooked in China's HIV prevention efforts. This study aims to examine men's practices and attitudes toward extramarital sexual relationships, motivations for visiting female sex workers (FSWs), perceptions of sexually transmitted infection (STI)/HIV risk and risk prevention strategies used. One hundred and eighty-six clients of FSWs with varying socio-economic statuses were interviewed in different sex work settings. Men described no conflict between their role as a client and a responsible family provider. They described social pressure from peers and business partners to visit FSWs, sexual pleasure and companionship as motivators to seek commercial sex. While some men reported no risks associated with visiting FSWs, others identified risks such as being arrested by the police, robbed by gangs and threatening the health of their families by contracting a STI. This study underscores the diversity of FSW clients and the need to understand the beliefs and behaviours of different client types to develop appropriate HIV prevention programmes. It also demonstrates the feasibility of recruiting different types of male clients, a hard-to-reach population for Chinese HIV prevention efforts. PMID- 22313091 TI - Combining dyad protonation and active site plasticity in BACE-1 structure-based drug design. AB - The ability of the BACE-1 catalytic dyad to adopt multiple protonation states and the conformational flexibility of the active site have hampered the reliability of computational screening campaigns carried out on this drug target for Alzheimer's disease. Here, we propose a protocol that, for the first time, combining quantum mechanical calculations, molecular dynamics, and conformational ensemble virtual ligand screening addresses these issues simultaneously. The encouraging results prefigure this approach as a valuable tool for future drug discovery campaigns. PMID- 22313092 TI - Ruthenium-catalyzed C-H bond arylations of arenes bearing removable directing groups via six-membered ruthenacycles. AB - Ruthenium-catalyzed direct arylations of phenols bearing removable directing groups were accomplished through carboxylate assistance via six-membered ruthenacycles as key intermediates. PMID- 22313093 TI - Tacrolimus only for breakfast .... PMID- 22313094 TI - Hemoglobin variability after renal transplantation is associated with mortality. AB - Anemia is a common problem after renal transplantation. Therefore, the patients are treated with erythropoietin stimulating agents (ESAs). The varying response to treatment contributes to hemoglobin variability, which might be associated with mortality. We conducted a retrospective cohort study of first kidney allograft recipients between 1990 and 2008 represented in the Austrian Transplant Registry. We included 1441 patients of whom 683 received ESAs at any time after transplantation. Cox regression with cubic splines and linear estimates and the purposeful selection algorithm of covariables were used. The measure of variability was the moving standard deviation computed at three monthly intervals for the entire graft life. The hazard ratio (HR) of mortality and graft loss in the spline models increased with hemoglobin variability. The linear HR for mortality was 2.35 (95% confidence interval 1.75-3.17, P<0.001) and functional graft loss 2.45 (1.76-3.40, P<0.001). In an adjusted Cox model (ESA use, hemoglobin, age, diabetes, days on dialysis, eGFR, biopsy confirmed acute rejection and year of transplantation), hemoglobin variability was associated with mortality (HR: 2.11; 1.51-2.94; P<0.001). No association with functional graft loss could be detected (HR: 1.34; 0.93-1.93; P=0.121). These findings suggest that hemoglobin variability is associated with mortality of renal allograft recipients. PMID- 22313095 TI - Jahn-Teller intersections induced by introduction of bending in linear polyatomics: study with HCNH, a selected molecular system. AB - Demonstration of onset of Jahn-Teller (JT) intersections, characterized by a topological phase of pi, on introduction of bending in the collinear tetra-atomic C(2)H(2)(+) cation, originally a Renner-Teller (RT) system, has raised interest in the study of the generality of this phenomenon. This interest has initiated similar study by shifting one external light atom from the collinear molecular axes of systems such as HCNH and HC(2)O. Recent studies have revealed that slightly bent HCNH poses a specialty in this regard and thus demands focused attention. In the present work we performed a combined study using both the potential intersections and the angular nonadiabatic coupling terms (NACTs) and report two new results: (i) The first result is the appearance of the JT conical intersections (ci's) between the two lowest states of a slightly bent HCNH molecule (1(2)A' and 1(2)A", originated from collinear X(2)Pi state) only with certain nonplanar configurations, in contrast to its appearance in C(S) configuration space (molecular plane) for slightly bent C(2)H(2)(+), HC(2)O, or some other tetra-atomics. This is also associated with the first time demonstration of Berry phase for such a single isolated ci for HCNH molecule. (ii) For energetically higher potentials of slightly bent HCNH, the present study reveals the existence of the intersection of the state 1(2)A" with the state 2(2)A' (originated from the collinear 1(2)Sigma(+) state); in contrast to the (1,2) ci this appears in the molecular plane. The search for ci's has been performed by varying the distances of the two H-atoms (designated as H(C) and H(N)) from the C-N axis as well as the dihedral angle phi between the two planes (H(C),C,N) and (C,N,H(N)). Existence of these JT ci's results in deterioration of a two-state Hilbert subspace (HSS) model in diabatization, while the proper choice of an n (>2)-state HSS circumvents this problem. PMID- 22313096 TI - Outpatient transfusions and occurrence of serious noninfectious transfusion related complications among US elderly, 2007-2008: utility of large administrative databases in blood safety research. AB - BACKGROUND: Transfusion-related acute lung injury (TRALI) and hemolytic transfusion reactions account for significant transfusion-related morbidity and mortality in the United States. Our study evaluated types and quantities of transfused components as well as occurrence of TRALI, ABO, and Rh incompatibilities among the US elderly in the institutional outpatient setting during 2007 to 2008. STUDY DESIGN AND METHODS: This retrospective claims-based study utilized the Centers for Medicare & Medicaid Services' large administrative databases. Transfusions were identified by recorded procedure and revenue center codes, while complications were ascertained via ICD-9-CM diagnosis codes. The study quantified blood use based on revenue center units. RESULTS: Among 26,054,242 and 25,662,864 Medicare elderly in 2007 and 2008, a total of 241,055 (0.9%) and 251,284 (1.0%) had outpatient transfusions. Leukoreduced red blood cells (LR-RBCs) was the most frequently transfused single blood component (60.1 and 61.3%, respectively) each year. Likewise, LR-RBCs and LR pheresis platelets (LR-PLTs) was the most frequent component combination (2.4 and 2.6%, respectively). TRALI rate comparison for RBCs and PLTs versus RBCs only showed higher rate for RBCs and PLTs (p = 0.033). In 2007 and 2008, ABO incompatibility rate comparison for irradiated (IR) LR-RBCs versus LR-RBCs showed higher rates for IR LR-RBCs (rate ratio [RR] 37.4, 95% confidence interval [CI] 10.6-132.6; and RR 31.3, 95% CI 11.6-84.4, respectively). CONCLUSION: This study shows potential usefulness of Medicare databases in assessment of blood utilization, transfusion-related complications, and risk factors among US elderly in the outpatient setting. It suggests limitations (e.g., need for several years of data to better assess rare complications) and importance of databases as hypothesis generating tool to supplement blood safety research. PMID- 22313097 TI - Association between the MTHFR C677T polymorphism and recurrent pregnancy loss: a meta-analysis. AB - BACKGROUND: C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) has been associated with recurrent pregnancy loss (RPL). However, results were conflicting. The aim of this study was to quantitatively summarize the evidence for MTHFR C677T polymorphism and RPL risk. METHODS: Electronic search of PubMed and the Chinese Biomedicine database was conducted to select studies. Case control studies containing available genotype frequencies of C677T were chosen, and odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association. RESULTS: The case-control studies including 2427 cases and 3118 controls were identified. The meta-analysis stratified by ethnicity showed that individuals with the homozygous TT genotype had increased risk of RPL (OR=1.574, 95% CI: 1.163-2.13, p=0.003), in Asians (OR=1.663, 95% CI: 1.012-2.731, p=0.045). Results among Caucasians did not suggest an association (OR=1.269, 95% CI: 0.914-1.761, p=0.155). A symmetric funnel plot, the Egger's test (p=0.285), and the Begg's test (p=0.529) were all suggestive of the lack of publication bias. The studies conducted in each of the defined number of pregnancy losses-two or more pregnancy losses, and three or more pregnancy losses showed no effect of the C677T polymorphism on RPL except for the TT versus CT+CT genotype comparison for the three or more pregnancy loss subgroup (OR=1.792, 95% CI: 1.187-2.704, p=0.005). CONCLUSION: This meta-analysis supports the idea that MTHFR C677T genotype is associated with increased risk of RPL, except for Caucasians. To draw comprehensive and true conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine associations between MTHFR C677T polymorphism and RPL. PMID- 22313098 TI - Longitudinal associations among youth depressive symptoms, peer victimization, and low peer acceptance: an interpersonal process perspective. AB - A longitudinal investigation was conducted to explicate the network of associations between depressive symptoms and peer difficulties among 486 fourth through sixth graders (M = 9.93 years). Parent and teacher reports of depressive symptoms; peer, self, and teacher reports of victimization; and peer reports of peer acceptance were obtained. A systematic examination of nested structural equation models provided support for a symptoms-driven model whereby depressive symptoms contributed to peer difficulties; no evidence was found for interpersonal risk or transactional models. Analyses further revealed that victimization mediated the association between prior depressive symptoms and subsequent peer acceptance. Results extend knowledge about the temporal ordering of depressive symptoms and peer difficulties and elucidate one process through which depressive symptoms disrupt peer relationships. PMID- 22313099 TI - Opioid maintenance in European prisons: is the treatment gap closing? PMID- 22313100 TI - Addictionology as biography: one hundred ways to have a successful career in addiction science. PMID- 22313101 TI - The diversion and misuse of pharmaceutical stimulants: what do we know and why should we care? AB - AIMS: To examine the literature pertaining to the diversion and misuse of pharmaceutical stimulants. METHODS: Relevant literature was identified through comprehensive MEDLINE, EMBASE and PubMed searches. RESULTS: The evidence to date suggests that the prevalence of diversion and misuse of pharmaceutical stimulants varies across adolescent and young adult student populations, but is higher than that among the general population, with the highest prevalence found among adults with attention deficit-hyperactive disorder (ADHD) and users of other illicit drugs. Concerns that these practices have become more prevalent as a result of increased prescribing are not supported by large-scale population surveys. Information on trends in misuse in countries where there have been recent increases in prescription and consumption rates, however, is limited. Little is known about the frequency and chronicity of misuse, or the extent of associated harms, particularly among those populations, i.e. adolescents, young adult student populations, those with ADHD and illicit drug users, where abuse may be more likely to occur. CONCLUSIONS: Continued monitoring of the diversion and misuse of pharmaceutical stimulants is of major clinical importance. Despite recognition of the abuse liability of these medications, there is a paucity of data on the prevalence, patterns and harms of diversion and misuse among populations where problematic use and abuse may be most likely to occur (e.g. adolescents, young adults, illicit drug users). Comprehensive investigations of diversion and misuse among these populations should be a major research priority, as should the assessment of abuse and dependence criteria among those identified as regular users. PMID- 22313102 TI - Current status of alcohol marketing policy--an urgent challenge for global governance. AB - AIMS: To review research literature and available information on the extent and impacts of marketing, current policy response and the interests engaged in the policy debate in order to inform recommendations for policy change on alcohol marketing. METHODS: Relevant literature, including systematic reviews and publicly available information (websites and participant observation) is reviewed and synthesized. RESULTS: Alcohol marketing has expanded markedly in the past 50 years and, while there remains uncertainty about the impact across the population, there is now clear evidence of its impact on the consumption of young people. Few countries have effective policy in place restricting alcohol marketing, and there is a lack of an international response to alcohol marketing which crosses national boundaries. The protection of alcohol marketing has been a major focus for vested interest groups and this has affected governmental response at national and international levels. There has been a lack of non governmental organization engagement. The policy response to tobacco marketing provides a clear contrast to that of alcohol marketing policy and provides a model for alcohol marketing policy. CONCLUSION: The global exposure of young people to alcohol marketing requires an urgent policy response. The Framework Convention on Tobacco Control provides an appropriate model for global governance to control alcohol marketing. There are extant examples of national level legislation achieving comprehensive bans with France's Loi Evin providing a feasible model. Resources from philanthropic organizations to allow non governmental organization engagement are urgently required, as is engagement by the governmental sector independent of commercial influence. PMID- 22313103 TI - Addiction and the science of history. AB - AIMS: To discuss the contributions historians have made to the addiction field, broadly construed to include licit and illicit drug use, drug policy, drug treatment and epidemiological and neuroscientific research. METHODS: Review of literature, highlighting specific contributions and controversies from recent research on the United States, the United Kingdom, China and world history. FINDINGS AND CONCLUSIONS: At the bar of addiction knowledge, historians make for excellent companions--until they turn quarrelsome. Historians' companionability arises from their ability to tell a particularly rich kind of story, one that blends structure, agency and contingency in a contextualizing narrative. Historians' occasional quarrelsomeness arises from their skepticism about the ascendant brain-disease paradigm, the medical and pharmaceutical establishments and the drug war, especially in its US incarnation. These enterprises have put some historians in a polemical frame of mind, raising doubts about the objectivity of their work and questions about the political orientation of historical scholarship (and, more generally, of social science research) in the field. PMID- 22313104 TI - Conversation with Robin Room. PMID- 22313105 TI - Commentary on Geels et al. (2012): The search for G spurs questions about E. PMID- 22313106 TI - Commentary on Rossow and Norstrom (2012): When should bars close? PMID- 22313107 TI - Commentary on Young & Havens (2012): A policymaker's perspective on drug use in Appalachia. PMID- 22313108 TI - Commentary on Higashi & Barendregt (2012): Smoking cessation therapies in Vietnam. PMID- 22313109 TI - Silk Road: eBay for drugs. PMID- 22313110 TI - Comment on Lader (2011). PMID- 22313111 TI - Structure-based function discovery of an enzyme for the hydrolysis of phosphorylated sugar lactones. AB - Two enzymes of unknown function from the cog1735 subset of the amidohydrolase superfamily (AHS), LMOf2365_2620 (Lmo2620) from Listeria monocytogenes str. 4b F2365 and Bh0225 from Bacillus halodurans C-125, were cloned, expressed, and purified to homogeneity. The catalytic functions of these two enzymes were interrogated by an integrated strategy encompassing bioinformatics, computational docking to three-dimensional crystal structures, and library screening. The three dimensional structure of Lmo2620 was determined at a resolution of 1.6 A with two phosphates and a binuclear zinc center in the active site. The proximal phosphate bridges the binuclear metal center and is 7.1 A from the distal phosphate. The distal phosphate hydrogen bonds with Lys-242, Lys-244, Arg-275, and Tyr-278. Enzymes within cog1735 of the AHS have previously been shown to catalyze the hydrolysis of substituted lactones. Computational docking of the high-energy intermediate form of the KEGG database to the three-dimensional structure of Lmo2620 highly enriched anionic lactones versus other candidate substrates. The active site structure and the computational docking results suggested that probable substrates would likely include phosphorylated sugar lactones. A small library of diacid sugar lactones and phosphorylated sugar lactones was synthesized and tested for substrate activity with Lmo2620 and Bh0225. Two substrates were identified for these enzymes, D-lyxono-1,4-lactone-5-phosphate and l-ribono-1,4-lactone-5-phosphate. The k(cat)/K(m) values for the cobalt substituted enzymes with these substrates are ~10(5) M(-1) s(-1). PMID- 22313112 TI - Hypoglycaemia during pregnancy in women with Type 1 diabetes. AB - AIMS: To explore incidence, risk factors, possible pathophysiological factors and clinical management of hypoglycaemia during pregnancy in women with Type 1 diabetes. METHODS: Literature review. RESULTS: In women with Type 1 diabetes, severe hypoglycaemia occurs three to five times more frequently in early pregnancy than in the period prior to pregnancy, whereas in the third trimester the incidence of severe hypoglycaemia is lower than in the year preceding pregnancy. The frequency distribution of severe hypoglycaemia is much skewed, as 10% of the pregnant women account for 60% of all recorded events. Risk factors for severe hypoglycaemia during pregnancy include a history with severe hypoglycaemia in the year preceding pregnancy, impaired hypoglycaemia awareness, long duration of diabetes, low HbA(1c) in early pregnancy, fluctuating plasma glucose values (<= 3.9 mmol/l or >= 10.0 mmol/l) and excessive use of supplementary insulin injections between meals. Pregnancy-induced nausea and vomiting seem not to be contributing factors. CONCLUSIONS: Striving for near normoglycaemia with focus on reduction of plasma glucose fluctuations during pregnancy should have high priority among clinicians with the persistent aim of improving pregnancy outcome among women with Type 1 diabetes. Pre-conception counselling, carbohydrate counting, use of insulin analogues, continuous subcutaneous insulin infusion (insulin pump) therapy and real-time continuous glucose monitoring with alarms for low glucose values might be relevant tools to obtain near-normoglycaemia without episodes of severe hypoglycaemia. PMID- 22313113 TI - RNT4 3'-UTR insertion/deletion polymorphisms are not associated with atrial septal defect in Chinese Han population: a brief communication. AB - Atrial septal defect (ASD) is a common type of congenital heart disease, which is defined as any communication through atrial septum. Several studies have revealed that genetic factors may influence the susceptibility of ASD. Recent studies have shown that reticulon 4 (RTN4) gene might be involved in some processes relevant to heart development, such as regulation of cell migration and vascular remodeling. This study aimed to evaluate RTN4 gene polymorphisms of CAA and TATC insertion/deletion in relation to the risk of ASD in Chinese Han population. A total of 175 ASD patients and 308 unrelated healthy controls were successfully investigated. The polymorphisms of patients were determined by polymerase chain reaction-polyacrylamide gel electrophoresis. There was no significant difference in the allele frequencies of CAA and TATC insertion/deletion in RNT4 gene between ASD patients and controls. The same results were seen in their genotypes. The present study suggests that CAA and TATC insertion/deletion polymorphisms of RNT4 gene may not be a useful marker to predict the susceptibility of ASD in Chinese Han population. PMID- 22313114 TI - Human fetal liver stromal cells expressing erythropoietin promote hematopoietic development from human embryonic stem cells. AB - Blood cells transfusion and hematopoietic stem cells (HSCs) transplantation are important methods for cell therapy. They are widely used in the treatment of incurable hematological disorder, infectious diseases, genetic diseases, and immunologic deficiency. However, their availability is limited by quantity, capacity of proliferation and the risk of blood transfusion complications. Recently, human embryonic stem cells (hESCs) have been shown to be an alternative resource for the generation of hematopoietic cells. In the current study, we describe a novel method for the efficient production of hematopoietic cells from hESCs. The stable human fetal liver stromal cell lines (hFLSCs) expressing erythropoietin (EPO) were established using the lentiviral system. We observed that the supernatant from the EPO transfected hFLSCs could induce the hESCs differentiation into hematopoietic cells, especially erythroid cells. They not only expressed fetal and embryonic globins but also expressed the adult-globin chain on further maturation. In addition, these hESCs-derived erythroid cells possess oxygen-transporting capacity, which indicated hESCs could generate terminally mature progenies. This should be useful for ultimately developing an animal-free culture system to generate large numbers of erythroid cells from hESCs and provide an experimental model to study early human erythropoiesis. PMID- 22313115 TI - Identification of beer bitter acids regulating mechanisms of gastric acid secretion. AB - Beer, one of the most consumed beverages worldwide, has been shown to stimulate gastric acid secretion. Although organic acids, formed by fermentation of glucose, are known to be stimulants of gastric acid secretion, very little is known about the effects of different types of beer or the active constituents thereof. In the present study, we compared the effects of different beers on mechanisms of gastric acid secretion. To investigate compound-specific effects on mechanisms of gastric acid secretion, organic acids and bitter compounds were quantified by HPLC-DAD and UPLC-MS/MS and tested in human gastric cancer cells (HGT-1) by means of a pH-sensitive fluorescent dye which determines the intracellular pH as an indicator of proton secretion. The expression of relevant genes, coding the H(+)/K(+)-ATPase, ATP4A, the histamine receptor, HRH2, the acetylcholine receptor, CHRM3, and the somatostatin receptor, SSTR2, was determined by qPCR. Ethanol and the organic acids succinic acid, malic acid, and citric acid were demonstrated to contribute to some extent to the effect of beer. The bitter acids comprising alpha-, beta-, and iso-alpha-acids were identified as potential key components promoting gastric acid secretion and up-regulation of CHRM3 gene expression by a maximum factor of 2.01 compared to that of untreated control cells with a correlation to their respective bitterness. PMID- 22313116 TI - Hydrogen-bond-mediated cascade reaction involving chalcones: facile synthesis of enantioenriched trisubstituted tetrahydrothiophenes. AB - A bifunctional squaramide catalyzed sulfa-Michael/aldol cascade reaction between 1,4-dithiane-2,5-diol and chalcones with a low catalyst loading has been developed. Trisubstituted tetrahydrothiophenes with three contiguous stereogenic centers are obtained in a highly stereocontrolled manner. Additionally, a remarkable temperature effect on reaction efficiency was observed and a synthetically potential gram-synthesis was also conducted. PMID- 22313117 TI - Protein profiling in potato (Solanum tuberosum L.) leaf tissues by differential centrifugation. AB - Foliar diseases, such as late blight, result in serious threats to potato production. As such, potato leaf tissue becomes an important substrate to study biological processes, such as plant defense responses to infection. Nonetheless, the potato leaf proteome remains poorly characterized. Here, we report protein profiling of potato leaf tissues using a modified differential centrifugation approach to separate the leaf tissues into cell wall and cytoplasmic fractions. This method helps to increase the number of identified proteins, including targeted putative cell wall proteins. The method allowed for the identification of 1484 nonredundant potato leaf proteins, of which 364 and 447 were reproducibly identified proteins in the cell wall and cytoplasmic fractions, respectively. Reproducibly identified proteins corresponded to over 70% of proteins identified in each replicate. A diverse range of proteins was identified based on their theoretical pI values, molecular masses, functional classification, and biological processes. Such a protein extraction method is effective for the establishment of a highly qualified proteome profile. PMID- 22313119 TI - Understanding how the distal environment directs reactivity in chlorite dismutase: spectroscopy and reactivity of Arg183 mutants. AB - The chlorite dismutase from Dechloromonas aromatica (DaCld) catalyzes the highly efficient decomposition of chlorite to O(2) and chloride. Spectroscopic, equilibrium thermodynamic, and kinetic measurements have indicated that Cld has two pH sensitive moieties; one is the heme, and Arg183 in the distal heme pocket has been hypothesized to be the second. This active site residue has been examined by site-directed mutagenesis to understand the roles of positive charge and hydrogen bonding in O-O bond formation. Three Cld mutants, Arg183 to Lys (R183K), Arg183 to Gln (R183Q), and Arg183 to Ala (R183A), were investigated to determine their respective contributions to the decomposition of chlorite ion, the spin state and coordination states of their ferric and ferrous forms, their cyanide and imidazole binding affinities, and their reduction potentials. UV visible and resonance Raman spectroscopies showed that DaCld(R183A) contains five coordinate high-spin (5cHS) heme, the DaCld(R183Q) heme is a mixture of five coordinate and six-coordinate high spin (5c/6cHS) heme, and DaCld(R183K) contains six-coordinate low-spin (6cLS) heme. In contrast to wild-type (WT) Cld, which exhibits pK(a) values of 6.5 and 8.7, all three ferric mutants exhibited pH independent spectroscopic signatures and kinetic behaviors. Steady state kinetic parameters of the chlorite decomposition reaction catalyzed by the mutants suggest that in WT DaCld the pK(a) of 6.5 corresponds to a change in the availability of positive charge from the guanidinium group of Arg183 to the heme site. This could be due to either direct acid-base chemistry at the Arg183 side chain or a flexible Arg183 side chain that can access various orientations. Current evidence is most consistent with a conformational adjustment of Arg183. A properly oriented Arg183 is critical for the stabilization of anions in the distal pocket and for efficient catalysis. PMID- 22313120 TI - A commentary on current perspectives on Mycobacterium avium subsp. paratuberculosis, Johne's disease and Crohn's disease: a review by Over et al. (2011). PMID- 22313121 TI - Fetomaternal hemorrhage in normal vaginal delivery and in delivery by cesarean section. AB - BACKGROUND: The objective was to determine the incidence and volume of fetomaternal hemorrhage (FMH) in normal vaginal delivery and in delivery by cesarean section. Determination of these variables would enable optimalization of guidelines for D alloimmunization prophylaxis. STUDY DESIGN AND METHODS: In a prospective cohort study, a total of 3457 examinations were performed, 2413 after normal vaginal delivery and 1044 after cesarean delivery. FMH was assessed by flow cytometry. (FMH is fetal red blood cell [RBC] volume; fetal blood volume is double [expected fetal hematocrit is 50%].) RESULTS: The fetal RBC volume diagnosed in maternal circulation after delivery ranged from insignificant FMH of not more than 0.1 mL to excessive FMH of 65.9 mL (median, 0.7; mean, 0.78; SD, 1.48). FMH of more than 2.5 mL (immunoglobulin [Ig] G anti-D insufficient dose 50 ug) was observed in 1.4% (49/3457) and excessive volumes of FMH of more than 5 mL (insufficient dose, 100 ug) in 0.29% (10/3457). Delivery by cesarean section presented a higher risk of incidence of FMH of more than 2.5 mL (odds ratio, 2.2; p = 0.004) when compared with normal vaginal delivery. It did not, however, present a significant risk factor for the incidence of excessive volumes of FMH of more than 5 mL. CONCLUSION: During normal vaginal delivery as well as during delivery by cesarean section, FMH of less than 5 mL occurs in the great majority of cases, and thus for the prevention of D alloimmunization, an IgG anti-D dose of 100 ug should be sufficient. Contrarily, only rarely does greater FMH occur and delivery by cesarean section does not present a risk factor. PMID- 22313122 TI - Nanomechanical properties of phospholipid microbubbles. AB - This study uses atomic force microscopy (AFM) force-deformation (F-Delta) curves to investigate for the first time the Young's modulus of a phospholipid microbubble (MB) ultrasound contrast agent. The stiffness of the MBs was calculated from the gradient of the F-Delta curves, and the Young's modulus of the MB shell was calculated by employing two different mechanical models based on the Reissner and elastic membrane theories. We found that the relatively soft phospholipid-based MBs behave inherently differently to stiffer, polymer-based MBs [Glynos, E.; Koutsos, V.; McDicken, W. N.; Moran, C. M.; Pye, S. D.; Ross, J. A.; Sboros, V. Langmuir2009, 25 (13), 7514-7522] and that elastic membrane theory is the most appropriate of the models tested for evaluating the Young's modulus of the phospholipid shell, agreeing with values available for living cell membranes, supported lipid bilayers, and synthetic phospholipid vesicles. Furthermore, we show that AFM F-Delta curves in combination with a suitable mechanical model can assess the shell properties of phospholipid MBs. The "effective" Young's modulus of the whole bubble was also calculated by analysis using Hertz theory. This analysis yielded values which are in agreement with results from studies which used Hertz theory to analyze similar systems such as cells. PMID- 22313123 TI - Insulin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study. AB - AIMS: To examine patient and physician beliefs regarding insulin therapy and the degree to which patients adhere to their insulin regimens. METHODS: Internet survey of 1250 physicians (600 specialists, 650 primary care physicians) who treat patients with diabetes and telephone survey of 1530 insulin-treated patients (180 with Type 1 diabetes, 1350 with Type 2 diabetes) in China, France, Japan, Germany, Spain, Turkey, the UK or the USA. RESULTS: One third (33.2%) of patients reported insulin omission/non-adherence at least 1 day in the last month, with an average of 3.3 days. Three quarters (72.5%) of physicians report that their typical patient does not take their insulin as prescribed, with a mean of 4.3 days per month of basal insulin omission/non-adherence and 5.7 days per month of prandial insulin omission/non-adherence. Patients and providers indicated the same five most common reasons for insulin omission/non-adherence: too busy; travelling; skipped meals; stress/emotional problems; public embarrassment. Physicians reported low patient success at initiating insulin in a timely fashion and adjusting insulin doses. Most physicians report that many insulin-treated patients do not have adequate glucose control (87.6%) and that they would treat more aggressively if not for concern about hypoglycaemia (75.5%). Although a majority of patients (and physicians) regard insulin treatment as restrictive, more patients see insulin treatment as having positive than negative impacts on their lives. CONCLUSIONS: Glucose control is inadequate among insulin-treated patients, in part attributable to insulin omission/non adherence and lack of dose adjustment. There is a need for insulin regimens that are less restrictive and burdensome with lower risk of hypoglycaemia. PMID- 22313124 TI - Ocular torsions and the subjective visual vertical with central vestibulo-ocular system lesions: independence disproved. AB - OBJECTIVES: Torsions of the eyes and deviations of the subjective visual vertical in roll occur regularly with disorders of the central vestibulo-ocular system. Although nearly universally coexisting, torsions and deviation have been held to be more or less independent of each other. MATERIALS AND METHODS: Angles of torsion were determined from fundus photographs in 55 subjects representing a variety of acute, focal, brainstem or cerebellar lesions. Measured torsions were contrasted with quantitative measurements of the subjective visual vertical. RESULTS: Torsions and deviations proved to be directly proportional, with a direction coefficient close to unity, and were strongly correlated (r = 0.86). CONCLUSIONS: Torsions and deviations are strongly dependent. This result should allow the generation of a more transparent pathophysiological model. From a practical point of view, measurements of deviation appeared more robust than those of torsion. PMID- 22313126 TI - Loving evidence for our prejudices. PMID- 22313125 TI - A classification of bioinformatics algorithms from the viewpoint of maximizing expected accuracy (MEA). AB - Many estimation problems in bioinformatics are formulated as point estimation problems in a high-dimensional discrete space. In general, it is difficult to design reliable estimators for this type of problem, because the number of possible solutions is immense, which leads to an extremely low probability for every solution-even for the one with the highest probability. Therefore, maximum score and maximum likelihood estimators do not work well in this situation although they are widely employed in a number of applications. Maximizing expected accuracy (MEA) estimation, in which accuracy measures of the target problem and the entire distribution of solutions are considered, is a more successful approach. In this review, we provide an extensive discussion of algorithms and software based on MEA. We describe how a number of algorithms used in previous studies can be classified from the viewpoint of MEA. We believe that this review will be useful not only for users wishing to utilize software to solve the estimation problems appearing in this article, but also for developers wishing to design algorithms on the basis of MEA. PMID- 22313127 TI - The real world is becoming clickable. AB - Although QR codes are considered new, they are no longer just an emerging technology. QR codes will revolutionize the educational process. PMID- 22313128 TI - Preparing for the future: what nurses need to know. AB - This column outlines some of the challenges and opportunities for nurses in the coming years. Implications for nursing practice and education are highlighted. PMID- 22313129 TI - Recommendations of The Future of Nursing report. AB - This column discusses the eight recommendations of the Institute of Medicine's The Future of Nursing report. PMID- 22313130 TI - Correlating novice nurses' perceptions of nursing orientation and first-year support with direct preceptor interventions. AB - Can preceptors correlate novices' experiences of the transition into nursing with interventions for support? A medical specialty preceptor committee representing more than 300 nurses at a large academic medical center conducted educational sessions for 46 inpatient nurses who had successfully completed orientation, but were still in the first year of practice. The novice forum used literature themes to guide exploration of the novices' perceptions. In the two novice forum sessions, the new nurses were invited to reflect on their experiences using a Turning Point Query((c)). The questions posed addressed the themes in the literature concerning the transition into professional practice. After noting and discussing the group responses, each preceptor committee representative held a discussion with two novices about their struggles and successes. The preceptors, after learning about novices' needs in this way, planned and directed forums for preceptor development of their peers. Concepts and teaching activities addressed the novices' identified concerns, which targeted greater need for feedback, affirmation, and debriefing, as well as reflective discussions on practice. This group thus correlated novices' perceptions with preceptor development activities. PMID- 22313133 TI - Genetic variants at 14q24.1 and breast cancer susceptibility: a fine-mapping study in Chinese women. AB - A single nucleotide polymorphism (SNP) rs999737 at 14q24.1 was identified as a susceptibility marker of breast cancer in a genome-wide association study of the European population, which was also confirmed by some of the following studies in populations of European descent. However, rs999737 is very rare or nonpolymorphic in non-Europeans including Chinese, and the role of other genetic variants at 14q24.1 has not been evaluated in populations of non-European descent. In this study, we first selected 21 common tagging SNPs (minor allele frequency [MAF] >0.05 in the Chinese population) by searching the Hapmap database, covering a linage disequilibrium region of more than 70 Kb at 14q24.1, and then conducted a two-stage study (stage I: 878 cases and 900 controls; stage II: 914 cases and 967 controls) to investigate the associations between these tagging SNPs and risk of breast cancer in a Chinese population. In stage I, two SNPs (rs2842346 and rs17828907) were identified to be significantly associated with breast cancer risk (p=0.030 and 0.027 for genotype distributions, respectively). However, no significant associations were found between these two SNPs and breast cancer risk in either stage II or the combined dataset. These findings suggest that common variants at 14q24.1 might not be associated with the risk of breast cancer in the Chinese population, which will need the replication in additional larger studies. PMID- 22313134 TI - Children's early child care and their mothers' later involvement with schools. AB - Theory and policy highlight the role of child care in preparing children for the transition into school. Approaching this issue in a different way, this study investigated whether children's care experiences before this transition promoted their mothers' school involvement after it, with the hypothesized mechanism for this link being the cultivation of children's social and academic skills. Analyses of 1,352 children (1 month-6 years) and parents in the NICHD Study of Early Child Care and Youth Development revealed that mothers were more involved at their children's schools when children had prior histories of high-quality nonparental care. This pattern, which was fairly stable across levels of maternal education and employment, was mediated by children's academic skills and home environments. PMID- 22313135 TI - Recombinant luteinizing hormone priming in multiple follicular stimulation for in vitro fertilization in downregulated patients. AB - Follicle development is controlled amongst other factors by pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) that act in synergy in completing follicle maturation. Exogenous gonadotropins, combined with gonadotropin-releasing hormone agonists, have been successfully used in patients with ovulatory disorders undergoing assisted reproduction. There is some evidence of a beneficial role of androgens or LH administration before FSH stimulation. This study was designed to verify whether the addition of LH in the early follicular phase, in downregulated patients undergoing follicular stimulation for assisted reproduction, would add benefits in terms of general outcomes and pregnancy rates. We compared two groups of patients one of which was treated with recombinant FSH (rFSH) alone and the other with rFSH plus recombinant LH (rLH), in the early follicular phase only. The number of eggs recovered was higher in the group treated with FSH only; however, the number of embryos available at transfer was similar in the two groups and, more importantly, the number of Grades I and II embryos was higher in the group pretreated with LH. Similarly, although biochemical pregnancy rate and clinical pregnancy rates were similar in both groups, a beneficial role of LH priming was demonstrated by the higher implantation rate achieved in these patients. PMID- 22313136 TI - Theoretical Study of Nascent Hydration in the Fe+(H2O)n system. AB - The interactions of the iron monocation with water molecules and argon atoms in the gas phase were studied computationally to elucidate recent infrared vibrational spectroscopy on this system. These calculations employ first principles all-electron methods performed with B3LYP/DZVP density functional theory. The ground state of Fe(+)(H(2)O) is found to be a quartet (M = 2S + 1 = 4, S is the total spin). Different binding sites for the addition of one or two argon atoms produce several low-lying states of different geometry and multiplicity in a relatively small energy range for Fe(+)(H(2)O)-Ar(2) and Fe(+)(H(2)O)(2)-Ar. In both species, quartet states are lowest in energy, and sextets and doublets lie at higher energies from the respective ground states. These results are consistent with the conclusion that the experimentally determined infrared photodissociation spectra (IRPD) of Fe(+)(H(2)O)-Ar(2) and Fe(+)(H(2)O)(2)-Ar are complicated because of the presence of multiple isomeric structures. The estimated IR bands for the symmetric and asymmetric O-H stretches from different isomers provide new insight into the observed IRPD spectra. PMID- 22313137 TI - On the construction and use of linear low-dimensional ventilation models. AB - The construction of fast reliable low-dimensional models is important for monitoring and control of ventilation applications. We employ a discrete Green's function approach to derive a linear low-dimensional ventilation model directly from the governing equations for indoor ventilation (i.e., the Navier-Stokes equations supplemented with a transport equation for indoor-pollutant concentration). It is shown that the flow equations decouple from the concentration equation when the ratio alpha of air-mass-flow rate to pollutant mass-flow rate increases to infinity. A low-dimensional discrete representation of the Green's function of the concentration equation can then be constructed, based on either numerical simulations or experiments. This serves as a linear model that allows for the reconstruction of concentration fields resulting from any type of pollutant-source distribution. We employ a suite of Reynolds-averaged Navier-Stokes (RANS) simulations to illustrate the methodology. We focus on a simple benchmark ventilation case under constant-density conditions. Discrete linear ventilation models for the concentration are then derived and compared with coupled RANS simulations. An analysis of errors in the discrete linear model is presented: dependence of the error on the (low-dimensional) resolution in the discrete model is quantified, and errors introduced by too low values of alpha are also investigated. PRACTICAL IMPLICATIONS: The paper introduces the derivation and construction of linear low-dimensional ventilation models, which allow reconstructing concentration fields resulting from any type of indoor pollutant-source distribution. Once constructed, these ventilation models are very efficient to estimate indoor contaminant concentration distributions, compared to direct CFD simulation approaches. Therefore, these models can facilitate monitoring and control of ventilation systems, to remove indoor contaminants. PMID- 22313138 TI - Factors influencing the successful integration of ambulance volunteers and first responders into ambulance services. AB - This study identifies the factors associated with the successful integration of ambulance volunteers and first responders into major ambulance services in Australia and New Zealand and then proposes a model of volunteer management for ambulance services. All ten members of the Australasian Council of Ambulance Authorities completed a questionnaire describing their volunteer and first responder staff, their numbers and deployment, and the management and integration of volunteers within their respective organisations. Eight senior managers responsible for ambulance volunteers and first responders from six States of Australia and one region of New Zealand subsequently participated in semistructured interviews. Analysis of interview transcripts and publicly available data revealed facilitative factors associated with strong, vibrant ambulance volunteer systems. These facilitative factors are commitment to volunteer models of service delivery; a degree of management decentralisation and volunteer input into decision-making; commitment of resources towards the volunteer model; and the organisational integration of volunteers into the ambulance service. The proposed facilitative model of volunteer management developed aims to encourage the adoption of positive and innovative strategies to improve the integration of ambulance volunteers and first responders in ambulance services. The model consists of four components: leadership; integrative processes; resource commitment; and relative autonomy. The first three of these relate directly to the organisation, while the fourth concerns the volunteers themselves. If these approaches were replicated more widely, a viable and effective volunteer emergency health response system could be established in those areas where it is uneconomic or impractical to provide a salaried ambulance service staffed with professionally qualified paramedics. PMID- 22313139 TI - Regioselective preferential nucleophilic addition of N-heterocycles onto haloarylalkynes over N-arylation of aryl halides. AB - The study of preferential addition of heterocyclic amines onto halo-substituted arylalkynes over N-arylation under various catalytic conditions is described. The present work supports and confirms the mechanistic pathway of our recent work on the tandem synthesis of indolo- and pyrrolo-[2,1-a]isoquinolines via hydroamination followed by oxidative addition and not vice versa. PMID- 22313141 TI - Evaluation of treatment continuation with alosetron by IBS-D severity criteria. AB - OBJECTIVES: This article evaluates the characteristics and treatment patterns of female patients with severe diarrhea-predominant irritable bowel syndrome (IBS-D) who were treated with alosetron under a risk management program. METHODS: Patients prescribed alosetron (2002-2009) and who voluntarily enrolled in the follow-up study were evaluated. Questionnaires were administered at baseline, Wk 5, Wk 10, and quarterly thereafter for <=1 year. Subgroup analyses were conducted in female patients with IBS-D >=6 months, stratified by IBS-D severity criteria met (1-3) from the alosetron prescribing information (treatment recommended in female patients meeting >=1 severity criterion). The voluntary and observational nature of the study are potential limitations, such that eligible patients in the clinical practice setting may have had more severe IBS-D, possibly representing a more motivated and homogeneous subpopulation of patients than the broader IBS-D population. RESULTS: A total of 7841 patients enrolled in the study; 92.4% were adult females; 79.4% (n = 6229) met label criteria. Mean follow-up time was ~10.3 months; 50.3% completed 1 year. Of the 6229 female patients, 76.9% met 3/3 severity criteria; 21.5% met 2/3 severity criteria; 1.4% met 1/3 severity criteria. The most common complaint was restriction of daily activities, followed by accidents/fecal incontinence, and stomach cramps/bloating. One-year treatment continuation was >=64% across IBS-D severity groups. CONCLUSIONS: One-year treatment continuation with alosetron was high, irrespective of the number of IBS D severity criteria met. Restriction of daily activities was the primary indicator of disease severity. These findings demonstrate that alosetron continues to be safely and effectively used under the risk management program, and appears to provide long-term benefit in appropriate patients with IBS-D. PMID- 22313142 TI - Cholesterol goal attainment in hypertensive patients: the impact of metabolic syndrome components. AB - BACKGROUND: Hypertension and dyslipidemia are potentially modifiable cardiovascular risk factors. METHODS: We studied hypertensive outpatients regarding goal attainment in controlling dyslipidemia, according to individual cardiovascular risk profile, following the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines. Factors of goal attainment for low-density lipoprotein cholesterol (LDL-C) were determined. RESULTS: Of the 1,202 patients, this study included 886 (73.8% female, 59.9+/-11.1 years) with available data to determine cardiovascular risk. Overall, 544 (61.4%) had LDL-C within the goal. Individuals with inappropriate LDL-C were older, had higher systolic blood pressure (SBP), and were more likely to have metabolic syndrome, diabetes, and cardiovascular disease (CVD) and were less likely to show a controlled blood pressure. There was a progressive worsening of LDL-C control as the number of components of metabolic syndrome increased. There was also a progressive increase in the percentage of patients with inappropriate LDL-C with the increase in cardiovascular risk. In a logistic regression model including LDL C inadequacy as a dependent variable, only age, diabetes, and CVD were predictors of inappropriate LDL-C. Moreover, even with correction for demographic and clinical variables, the inappropriate LDL-C was an independent predictor of CVD. CONCLUSIONS: The control of dyslipidemia in hypertensive patients is far from ideal and results are even worse in individuals with CVD. PMID- 22313143 TI - The cost of diagnosing Type 2 diabetes mellitus by clinical opportunistic screening in general practice. AB - AIMS: Type 2 diabetes is associated with serious complications and shortens life. Its prevalence is increasing rapidly worldwide and no cure is available. One logical response is to diagnose the condition as early as possible. Clinical opportunistic screening is one mechanism for making the diagnosis before symptoms are reported. This paper reports the cost of using this technique in UK general practice. METHODS: In one UK general practice, the electronic medical records were searched to determine the number of blood glucose and oral glucose tolerance tests undertaken for non-pregnant adults without known diabetes over three consecutive years. The laboratory, staff and administrative costs associated with these screening tests were calculated. The records of all patients newly diagnosed with Type 2 diabetes during the same period were reviewed to identify diagnoses made by clinical opportunistic screening. Total costs were divided by the number of diagnoses to determine a cost per diagnosis detected by opportunistic screening. RESULTS: During the study period, 5720 screening tests were conducted for 2763 patients. Over the 3 years, 86 patients were diagnosed with Type 2 diabetes, 54 (63%) via screening (yield 2.0%; number needed to screen 51.2). The screening costs totalled L 20,372. The average cost per new screen detected diagnosis was L 377. CONCLUSIONS: Almost two-thirds of new cases of Type 2 diabetes can be detected before symptoms are reported, at reasonable cost by opportunistic screening in general practice, without the use of extra resources. As an affordable alternative to population screening, clinical opportunistic screening merits further consideration. PMID- 22313144 TI - Circles on pommel horse with a suspended aid: spatio-temporal characteristics. AB - A suspended aid is popular for learning circles and for refining circle technique on pommel horse. The aim of this study was to investigate the effect of using a suspended aid on the biomechanical characteristics of circles. This first study focused specifically on the spatio-temporal characteristics of circles. Eighteen gymnasts performed three sets of 10 circles with and without a suspended aid on a pommel horse under which two force plates were set. Three-dimensional coordinates were acquired using 13 Qualisys motion tracking cameras operating at 100 Hz. The results showed that circles with the aid were characterised by a smaller body flexion angle, a greater shoulder angle, a greater ankle circle diameter, earlier hand releases, and a longer total duration. In contrast, the body lateral flexion angle, the arm-leaning angle, and the shoulder circle diameter remained relatively similar to circles without the aid. It was confirmed that circles with the aid actually appeared to be more desirable in terms of the movement amplitude. In this sense, a suspended aid could function as spotting, which is often used for a progression to learn gymnastics skills and to let gymnasts experience a desired movement pattern. PMID- 22313145 TI - Serum visfatin levels in women with polycystic ovary syndrome. AB - The aim of this study is to determine the serum levels of visfatin in patients with polycystic ovary syndrome (PCOS) and to understand its correlations with other metabolic and hormonal parameters. Thirty-seven patients with PCOS and 30 women without concomitant disease were included in this study. Serum visfatin levels were similar in patients with PCOS and control group. Visfatin levels were higher in normal weight PCOS when compared with obese PCOS, but it did not reach statistical significance. Visfatin levels correlated negatively with fasting blood glucose, total cholesterol (TC), low-density lipoprotein (LDL) and lipoprotein-a levels in PCOS patients. CRP levels increased both in obese PCOS and in obese controls. Plasma visfatin levels had no correlation with homeostasis model assessment-insulin resistance and fasting insulin levels, but the negative correlation between plasma visfatin levels and lipoprotein-a, fasting plasma glucose, TC and LDL levels may indicate a role for visfatin in cardiovascular disease independent of insulin resistance. PMID- 22313146 TI - Reactivation of hepatitis B virus with mutated hepatitis B surface antigen in a liver transplant recipient receiving a graft from an antibody to hepatitis B surface antigen- and antibody to hepatitis B core antigen-positive donor. AB - BACKGROUND: Fresh-frozen plasma (FFP) may contain antibodies to hepatitis B surface antigen (HBsAg, anti-HBs). These anti-HBs may lead to a misinterpretation of the actual hepatitis B immune status. Furthermore, they may not only confer protection against hepatitis B virus (HBV), but may also favor the selection of HBsAg mutants. CASE REPORT: We report a case of de novo HBV infection in a HBV naive recipient with alcoholic liver disease, who received a liver from a donor with antibodies to hepatitis B core antigen (HBcAg, anti-HBc) and anti-HBs. RESULTS: A lookback investigation revealed the following: 1) Due to anti-HBs passively acquired through FFP, the recipient was considered immune to HBV and did not receive anti-HBV prophylaxis. 2) Within 1 year after transplantation he developed hepatitis B in absence of any elevated liver enzymes after the anti-HBs by FFP declined. 3) Despite an infection with HBV-containing wild-type HBcAg, the patient did not seroconvert to anti-HBc positivity. 4) The replicating HBV encoded two HBsAg mutations, first sQ129R and 4 months later sP127S. They map to the highly conserved "alpha" determinant of the HBsAg loop. CONCLUSION: 1) Passive transfer of anti-HBs from FFP led to an erroneous pretransplant diagnosis of HBV immunity when the patient was in fact HBV-naive. 2) HBsAg mutations might have been selected in escape from donor's actively produced anti-HBs and the recipient's anti-HBs by FFP might have favored this selection. 3) It is doubtful whether hepatitis B immunoglobulin could have prevented the reactivation. 4) Antiviral prophylaxis would have been crucial. PMID- 22313147 TI - Transvaginal color Doppler sonography predicts ovarian interstitial fibrosis and microvascular injury in women with ovarian endometriotic cysts. AB - OBJECTIVE: To determine novel predictors of ovarian interstitial fibrosis and microvascular injury associated with ovarian endometriotic cysts (OECs). DESIGN: Case-control study. SETTING: The gynecology unit of an affiliated hospital in China. POPULATION: Women <40 years of age with OECs or benign ovarian tumors (controls). METHODS: Transvaginal color Doppler sonography was performed preoperatively to detect ovarian interstitial flow. Postoperatively, expressions of transforming growth factor-beta1 (TGF-beta1) and thrombospondin-1 (TSP-1), as well as microvessel density in ovarian interstitial, were analyzed using immunohistochemistry. MAIN OUTCOME AND MEASURES: Ovarian interstitial flow and expressions of TGF-beta1, TSP-1, and microvessel density. RESULTS: Compared with controls, ovarian interstitial flow in the study group was decreased and arterial spectra indicated significantly higher resistance indices. Microvessel density was reduced, but TGF-beta1 and TSP-1 were elevated in the study group. There was a positive correlation between TGF-beta1 and TSP-1. There were negative correlations between TGF-beta1 and microvessel density, and between TSP-1 and microvessel density. Microvessel density and resistance indices were negatively correlated, whereas the correlations of TGF-beta1 and TSP-1 with resistance indices were positive. CONCLUSIONS: Resistance indices are consistent with pathological indices. Changes in resistance indices in ovaries with endometriosis are related to interstitial fibrosis and microvascular injury. PMID- 22313149 TI - SVOC exposure indoors: fresh look at dermal pathways. AB - This paper critically examines indoor exposure to semivolatile organic compounds (SVOCs) via dermal pathways. First, it demonstrates that--in central tendency--an SVOC's abundance on indoor surfaces and in handwipes can be predicted reasonably well from gas-phase concentrations, assuming that thermodynamic equilibrium prevails. Then, equations are developed, based upon idealized mass-transport considerations, to estimate transdermal penetration of an SVOC either from its concentration in skin-surface lipids or its concentration in air. Kinetic constraints limit air-to-skin transport in the case of SVOCs that strongly sorb to skin-surface lipids. Air-to-skin transdermal uptake is estimated to be comparable to or larger than inhalation intake for many SVOCs of current or potential interest indoors, including butylated hydroxytoluene, chlordane, chlorpyrifos, diethyl phthalate, Galaxolide, geranyl acetone, nicotine (in free base form), PCB28, PCB52, Phantolide, Texanol and Tonalide. Although air-to-skin transdermal uptake is anticipated to be slow for bisphenol A, we find that transdermal permeation may nevertheless be substantial following its transfer to skin via contact with contaminated surfaces. The paper concludes with explorations of the influence of particles and dust on dermal exposure, the role of clothing and bedding as transport vectors, and the potential significance of hair follicles as transport shunts through the epidermis. PRACTICAL IMPLICATIONS: Human exposure to indoor pollutants can occur through dietary and nondietary ingestion, inhalation, and dermal absorption. Many factors influence the relative importance of these pathways, including physical and chemical properties of the pollutants. This paper argues that exposure to indoor semivolatile organic compounds (SVOCs) through the dermal pathway has often been underestimated. Transdermal permeation of SVOCs can be substantially greater than is commonly assumed. Transport of SVOCs from the air to and through the skin is typically not taken into account in exposure assessments. Yet, for certain SVOCs, intake through skin is estimated to be substantially larger than intake through inhalation. Exposure scientists, risk assessors, and public health officials should be mindful of the dermal pathway when estimating exposures to indoor SVOCs. Also, they should recognize that health consequences vary with exposure pathway. For example, an SVOC that enters the blood through the skin does not encounter the same detoxifying enzymes that an ingested SVOC would experience in the stomach, intestines, and liver before it enters the blood. PMID- 22313150 TI - Chemical dynamics simulations of X- + CH3Y -> XCH3 + Y- gas-phase S(N)2 nucleophilic substitution reactions. Nonstatistical dynamics and nontraditional reaction mechanisms. AB - Extensive classical chemical dynamics simulations of gas-phase X(-) + CH(3)Y -> XCH(3) + Y(-) S(N)2 nucleophilic substitution reactions are reviewed and discussed and compared with experimental measurements and predictions of theoretical models. The primary emphasis is on reactions for which X and Y are halogen atoms. Both reactions with the traditional potential energy surface (PES), which include pre- and postreaction potential energy minima and a central barrier, and reactions with nontraditional PESs are considered. These S(N)2 reactions exhibit important nonstatistical atomic-level dynamics. The X(-) + CH(3)Y -> X(-)---CH(3)Y association rate constant is less than the capture model as a result of inefficient energy transfer from X(-)+ CH(3)Y relative translation to CH(3)Y rotation and vibration. There is weak coupling between the low frequency intermolecular modes of the X(-)---CH(3)Y complex and higher frequency CH(3)Y intramolecular modes, resulting in non-RRKM kinetics for X(-)---CH(3)Y unimolecular decomposition. Recrossings of the [X--CH(3)--Y](-) central barrier is important. As a result of the above dynamics, the relative translational energy and temperature dependencies of the S(N)2 rate constants are not accurately given by statistical theory. The nonstatistical dynamics results in nonstatistical partitioning of the available energy to XCH(3) +Y(-) reaction products. Besides the indirect, complex forming atomic-level mechanism for the S(N)2 reaction, direct mechanisms promoted by X(-) + CH(3)Y relative translational or CH(3)Y vibrational excitation are possible, e.g., the roundabout mechanism. PMID- 22313151 TI - The effect of garlic supplements and phytochemicals on the ADMET properties of drugs. AB - INTRODUCTION: Garlic supplements have received wide public attention because of their health-beneficial effects. Although these products are considered as innocuous, several case reports and studies have shown the capacity of individual garlic phytochemicals/supplements to interfere with drug pharmacokinetics. AREAS COVERED: This review covers recently published literature on garlic chemistry and composition, and provides a thorough review of published studies evaluating drug garlic interactions. The authors illustrate the mechanisms underlying pharmacokinetic interactions, which could serve as important highlights in further research to explain results for drugs with narrow therapeutic indices or for drugs, utilizing multiple absorption, distribution and metabolism pathways. EXPERT OPINION: To increase the relevance of further research on safety and efficacy of garlic supplements and phytochemicals, their composition should be addressed before conducting in vitro or in vivo research. It is also strongly recommended to characterize in vitro formulation performance to assess the rate and extent of garlic phytochemical release in order to anticipate the in vivo impact on the pharmacokinetics of concomitantly consumed drugs. The main conclusion of this review is that the impact of garlic on different stages of pharmacokinetics, especially on drug absorption and metabolism, is drug specific and dependent on the type/quality of utilized supplement. PMID- 22313152 TI - A network method of measuring affiliation-based peer influence: assessing the influences of teammates' smoking on adolescent smoking. AB - Using a network analytic framework, this study introduces a new method to measure peer influence based on adolescents' affiliations or 2-mode social network data. Exposure based on affiliations is referred to as the "affiliation exposure model." This study demonstrates the methodology using data on young adolescent smoking being influenced by joint participation in school-based organized sports activities with smokers. The analytic sample consisted of 1,260 American adolescents from ages 10 to 13 in middle schools, and the results of the longitudinal regression analyses showed that adolescents were more likely to smoke as they were increasingly exposed to teammates who smoke. This study illustrates the importance of peer influence via affiliation through team sports. PMID- 22313153 TI - Insulin initiation in elderly patients with type 2 diabetes in France: a subpopulation of the LIGHT study. AB - OBJECTIVE: To examine the management of basal insulin analogue initiation in combination with oral antidiabetic drug (OAD) therapy in elderly patients with type 2 diabetes (aged >=70 years) by physicians via comparison to the same treatment strategy in younger individuals (<70 years). METHODS: This subanalysis of a longitudinal observational study took place in a clinical setting across 761 health centres in France. A total of 1802 patients with type 2 diabetes (519 aged >=70 years and 1283 aged <70 years) participated. The primary endpoint of this study was to assess the management of basal insulin analogue initiation along with OADs in elderly patients (aged >=70 years) by physicians. Secondary endpoints included HbA(1c), percentage of patients achieving HbA(1c) target (<7.0%), fasting plasma glucose, weight change (kg) and hypoglycaemia. RESULTS: The initial mean (standard deviation [SD]) basal insulin analogue dose was similar in the elderly and younger patient subgroups (0.18 [0.09] IU/kg vs. 0.18 [0.11] IU/kg, respectively; not significant [NS]). The mean (SD) number of injections per day was also comparable between age groups (1 [0.2] per day vs. 1 [0.3] per day, respectively for elderly and younger patients; NS). Three months after initiation of long-acting insulin analogue therapy, 3.5% (n = 18) of elderly patients ceased insulin treatment. At study end, the mean (SD) HbA(1c) for elderly patients was 7.6% (0.9%), and for younger patients it was 7.5% (0.9%). Also, the rate of overall hypoglycaemia was comparable in the elderly and younger patients (0.38 [1.2] events/patient/month vs. 0.35 [1.0] events/patient/month, respectively; NS). Limitations of this study include the possibility of inaccurate patient recall of hypoglycaemic events and deficiencies in the adverse events reporting system. CONCLUSION: Basal insulin analogues were successfully initiated in elderly patients in combination with OAD therapies and were shown to provide effective glycaemic control. Levels of hypoglycaemia were also similar to those seen in younger patients. PMID- 22313154 TI - Effect of saxagliptin as add-on therapy in patients with poorly controlled type 2 diabetes on insulin alone or insulin combined with metformin. AB - OBJECTIVE: To evaluate efficacy and safety of saxagliptin as add-on therapy in patients with type 2 diabetes (T2D) with inadequate glycemic control on insulin alone or combined with metformin. METHODS: Adults (n = 455) with HbA(1c) 7.5-11% on stable insulin therapy (30-150 U/day +/- metformin) for at least 8 weeks were stratified by metformin use and randomly assigned 2:1 to receive saxagliptin 5 mg or placebo once daily for 24 weeks. Patients were to maintain stable insulin doses but these could be decreased to reduce risk of hypoglycemia. Patients with hyperglycemia or substantially increased insulin use were rescued with a flexible insulin regimen and remained in the study. Metformin doses were kept stable. The primary efficacy endpoint was change in HbA(1c) from baseline to week 24 (or rescue). RESULTS: Patients treated with saxagliptin versus placebo had significantly greater reductions in adjusted mean HbA(1c) (difference: -0.41%, p < 0.0001), postprandial glucose (PPG) 180-minute area under the curve (-3829.8 mg.min/dL, p = 0.0011), and 120-minute PPG (-23.0 mg/dL, p = 0.0016) at 24 weeks. Treatment with saxagliptin resulted in similar reductions in HBA(1c) relative to placebo, irrespective of metformin treatment. At 24 weeks, difference in adjusted mean fasting plasma glucose for saxagliptin versus placebo was -4.02 mg/dL (p = 0.3958); 17.3% and 6.7% of patients in the saxagliptin and placebo groups, respectively, achieved HbA(1c) < 7%. Mean change from baseline in body weight at week 24 was 0.39 kg for saxagliptin and 0.18 kg for placebo. Hypoglycemia was reported in 18.4% and 19.9% of patients in the saxagliptin and placebo groups, respectively (confirmed hypoglycemia: 5.3%, 3.3%). Other adverse events reported in at least 5% of patients were urinary tract infection (saxagliptin, placebo: 5.9%, 6.0%), influenza (3.0%, 6.6%), and pain in extremity (1.6%, 6.0%). CONCLUSIONS: Saxagliptin 5-mg once-daily add-on therapy improves glycemic control in T2D patients on insulin alone or combined with metformin and is generally well tolerated. NCT00757588. PMID- 22313155 TI - Case report: a most peculiar family with spontaneous, recurrent ovarian hyperstimulation syndrome. AB - Ovarian hyperstimulation syndrome (OHSS) mostly occurs as a complication of induction of ovulation. However, rarely, it may occur spontaneously at the beginning of a natural pregnancy and in the absence of any assisted reproductive treatment. Spontaneous OHSS has been reported in pregnant women affected by hypothyroidism, polycystic ovary syndrome, gonadotropin-producing pituitary adenoma, but also in normal pregnancies. The aetiology of this condition is still unclear. We hereby report on a case of spontaneous, familial, recurrent OHSS in a 26-year-old primipara whose first-degree cousin, paternal grandmother and a number of other members of her father's family had suffered from a similar condition. This case seems to support the concept of a genetic predisposition for spontaneous OHSS thereby suggesting the need for preventive and therapeutic strategies. PMID- 22313156 TI - Gestational diabetes, obesity, and metabolic syndrome diagnosed during pregnancy. AB - BACKGROUND: The aim was to analyze the impact of obesity on women with gestational diabetes mellitus (GDM) and the association of obesity and GDM with the metabolic syndrome. METHODS: In a retrospective study, the data of 233 obese women with GDM were compared with the data of 96 women with GDM and normal weight. RESULTS: Significantly higher fasting glycemia before the oral glucose tolerance test (5.2+/-1.1 mmol/L vs. 4.5+/-0.8 mmol/L, P<0.00001) and higher frequency of hypertensive disorders of pregnancy (26.2% vs. 9.4%, P=0.0003) were found in obese women with GDM than in GDM women of normal weight. These women needed insulin therapy more often (18.9% vs. 8.3%, P=0.007). Also 31 (13.3 %) of them had chronic hypertension as compared with 3.1% in women of normal weight (P=0.003). These 31 women had three components necessary for diagnosing of metabolic syndrome according to the World Health Organization-impaired glucose tolerance, obesity, and hypertension. No difference in gestational age and mean weight of their newborns was found, but newborns of obese GDM women with metabolic syndrome components more often were significantly macrosomic with features of diabetic fetopathy and had more often symptoms of hypoglycemia after birth. CONCLUSIONS: The presence of obesity and GDM has a significant impact on both maternal and fetal complications. The metabolic syndrome can be diagnosed not only after pregnancy but also during pregnancy. PMID- 22313157 TI - Hyperuricemia and microalbuminuria are separately and independently associated with prehypertension among Chinese Han women. AB - BACKGROUND: Whether hyperuricemia and microalbuminuria are separately associated with prehypertension among Chinese Han women is controversial. METHODS: Information was collected from physical examinations, personal interviews, and blood and urine samples. Associations of hyperuricemia and microalbuminuria with hypertension and prehypertension were analyzed by using multivariate nonconditional logistic regression models in 1,773 women aged >=30 years. RESULTS: Both average systolic and diastolic blood pressure increased with uric acid and urinary albumin-to-creatinine ratio levels (all trend P values<0.001). When subjects with microalbuminuria or using antihypertensive medication were excluded, individuals with a uric acid level in the 2(nd), 3(rd), and 4(th) quartiles of uric acid were more likely to have prehypertension than those with a uric acid level in the lowest quartile [odds ratio (OR)=1.50, 95% confidence interval (CI) 1.02-2.19; OR=1.69, 95% CI 1.12-2.56; OR=2.67, 95% CI 1.57-4.53). After exclusion of subjects with diabetes or hyperuricemia or using antihypertensive medication, compared with normotensives, individuals with high blood pressure status of prehypertension were more likely to have microalbuminuria (OR=1.83, 95% CI 1.12-2.99). Additionally, microalbuminuria was positively associated with blood pressure levels (trend P value<0.001). CONCLUSIONS: Hyperuricemia and microalbuminuria are separately and independently associated with prehypertension among Chinese Han women. PMID- 22313158 TI - Prevalence of haematuria positively associated with urine albumin excretion in Type 2 diabetes. AB - AIMS: Some guidelines or studies consider haematuria an indication for renal biopsy or a potential cause of albuminuria that precludes accurate assessment of urinary albumin excretion. This study examined the justification of excluding haematuria in interpreting urinary albumin excretion in patients with Type 2 diabetes and its associations with other diabetes-related variables. METHODS: Between May and November 2008, patients with Type 2 diabetes at a single centre with data on urinary albumin excretion and urinalysis in the same urine sample were recruited. Urinary albumin excretion was determined by urine albumin/creatinine ratio in spot urine. Diagnosis of haematuria was made by positive urine occult blood from 1+ to 4+ and/or presence of more than nine red blood cells/ml in urinalysis. Demographic, anthropometric, clinical and laboratory variables and diabetes-associated complications were analysed. RESULTS: In total, 743 patients were enrolled. Prevalence of haematuria among patients with normoalbuminuria, microalbuminuria, or macroalbuminuria was 8.7% (n = 13), 16.1% (n = 67) and 35.8% (n = 64), respectively. Urine albumin/creatinine ratio was significantly higher, while macroalbuminuria was more common in patients with haematuria (n = 144) than in those without (n = 599). Multiple regression analysis identified urine albumin/creatinine ratio (odds ratio 1.33, P = 0.01) and macroalbuminuria (odds ratio 2.66, P = 0.01) as the only independent predictors of haematuria. Moreover, urine albumin/creatinine ratio was an independent predictor of haematuria in the macroalbuminuria subgroup (odds ratio 1.30, P = 0.04). CONCLUSIONS: Increased urine albumin/creatinine ratio and macroalbuminuria were the only independent predictors of haematuria in patients with Type 2 diabetes, raising questions on the justifications of excluding haematuria in interpreting urinary albumin excretion in patients with Type 2 diabetes and including haematuria as an indication for renal biopsy in those with macroalbuminuria. PMID- 22313159 TI - Chlorine and carbon isotopes fractionation during volatilization and diffusive transport of trichloroethene in the unsaturated zone. AB - To apply compound-specific isotope methods to the evaluation of the origin and fate of organic contaminants in the unsaturated subsurface, the effect of physicochemical processes on isotope ratios needs to be known. The main objective of this study is to quantify chlorine and carbon isotope fractionation during NAPL-vapor equilibration, air-water partitioning, and diffusion of trichloroethene (TCE) and combinations of these effects during vaporization in porous media. Isotope fractionation is larger during NAPL-vapor equilibration than air-water partitioning. During NAPL-vapor equilibration, carbon, and chlorine isotope ratios evolve in opposite directions although both elements are present in the same bond, with a normal isotope effect for chlorine (epsilon(Cl) = -0.39 +/- 0.030/00) and an inverse effect for carbon (epsilon(C) = +0.75 +/- 0.040/00). During diffusion-controlled vaporization in a sand column, no significant carbon isotope fractionation is observed (epsilon(C) = +0.10 +/- 0.050/00), whereas fairly strong chlorine isotope fractionation occurs (epsilon(Cl) = -1.39 +/- 0.060/00) considering the molecular weight of TCE. In case of carbon, the inverse isotope fractionation associated with NAPL-vapor equilibration and normal diffusion isotope fractionation cancel, whereas for chlorine both processes are accompanied by normal isotope fractionation and hence they cumulate. A source of contamination that aged might thus show a shift toward heavier chlorine isotope ratios. PMID- 22313160 TI - Topical delivery of antioxidants. AB - Reactive oxygen species (ROS) and free radicals have been implicated in a number of diseases and disorders, and the skin, for its localization, is exposed to a large number of environmental threats. Free radical scavengers and antioxidants have thus been proposed as protective or therapeutic agents against ROS-mediated injuries. Oral treatment with several antioxidants has been reported to provide skin protection against deleterious effects of ultraviolet radiation. Topical delivery of antioxidants has increasingly gained interest and development, especially by offering better targeting to the upper skin layer. However, the topical delivery of antioxidants for dermal action is a challenging research field since the molecules are, in general, susceptible to degradation. The search for a new delivery system that, simultaneously, preserves the antioxidant stability and enhances its deposition on the skin, opened a new chapter in drug delivery design. Nanocarriers have been successful in enhancing the clinical efficiency of several drugs. More recent approaches in modulating through the skin delivery led to the development of specialized nanoparticulated systems. The first part of this article presents a review of the potential of antioxidants as pharmacological agents in ROS related diseases, with a special focus on oxidative stress implicated skin pathologies: ROS formation and natural protection against ROS toxicity, ROS-mediated skin damage and skin protection by antioxidants. In the second part of this work, we present reported formulation strategies for dermal delivery of antioxidants focusing on the nanoparticulated systems developed in recent years. PMID- 22313161 TI - Development and pharmacological evaluation of a PEG based nanoparticulate camptothecin analog for oral administration. AB - The aim of this study was to formulate polyethylene glycol (PEG) based nanoparticulate camptothecin analog for oral administration and to evaluate its pharmacological activity. Camptothecin analog (CA) belongs to topoisomerase-I inhibitor class of compounds with proven antitumor activity but exhibits poor solubility. To enhance solubility and oral bioavailability, a PEG based nanoparticulate formulation was developed using a high pressure homogenization technique. The saturation solubility and dissolution characteristics of the nanoparticulate formulation were investigated and compared with as-is drug formulation to ascertain the impact of particle size on drug dissolution in physiologically relevant dissolution media. Systemic exposure of nanoparticulate formulation were evaluated in Wistar rats for increase in the rate and extent of drug absorption. The antitumor activity of nanoparticulate formulation was evaluated on human tumor xenografts (NCI-H460 cell lines) grown in athymic nude mice and compared with a positive control, Irinotecan Hydrochloride administered intravenously. The saturation solubility and dissolution rate of the nanoparticulate formulation were significantly higher as compared to as-is drug formulation. Pharmacokinetic (PK) studies in Wistar rats indicated significant increase in the rate and extent of absorption for the nanoparticulate formulation. Pharmacological activity of nanoparticles in athymic nude mice with implanted tumors revealed that the tumor inhibition activity was equivalent to Irinotecan Hydrochloride intravenous formulation with comparable safety profile at lower doses. These studies demonstrated the feasibility of developing a safe and efficacious oral formulation for a sparingly soluble camptothecin analog that may provide a viable, patient compliant and, cost effective option for the treatment of solid tumors. PMID- 22313162 TI - Evaluation of pH triggers in situ porous controlled release micro balloon delivery of amoxicillin for eradication of Helicobacter pylori. AB - Helicobacter pylori reside in the gastric mucus layer and at the mucus-epithelial cell interface wherein access of antimicrobial drug to the infection site is restricted both from the stomach and from the gastric blood supply. The aim of the present study was to develop pectin or gellan gum blended sodium alginate microspheres in order to eradicate gastric Helicobacter pylori. The percentage drug release and mucoadhesion were decrease on increasing the calcium chloride in the formulation dispersion. Curing time significantly effected encapsulation efficiency and was not affected % drug content, % buoyancy, and particle size and drug release. The efficacy of the optimized formulation was evidenced by absence of amplified bacterial gene in treated stomach tissue of Mongolian gerbils as observed using in polymerase chain reaction. The results demonstrate that the developed formulation of Am has potential to eradicate Helicobacter pylori by targeted and prolonged retention at gastric mucosa. PMID- 22313163 TI - Effect of sugar additives on stability of human serum albumin during vacuum foam drying and storage. AB - No literature on the protein stabilization of human serum albumin (HSA) by vacuum foam drying (VFD) has been reported. The purpose of this study was to investigate the effect of sugar-additive systems on the stability of HSA by VFD. For the assessment, HSA was formulated with sucrose and mannitol, respectively, alone or in combination with stabilizers, which were vacuum foam dried and stored at 25C. Protein content of the resulting dried formulations was analyzed by Lowry method. Fourier-transform infrared spectroscopy (FT-IR) analysis of the HSA secondary structure showed apparent protein structure-stabilizing effects of the amorphous sugar and phosphate combination during the VFD. In particular, sucrose-sodium phosphate monobasic mixture provide an interesting alternative to pure saccharide formulations due to their high glass transition temperatures and their increased ability to maintain a low melting transition temperature in the presence of small amounts of water. Inhibition of the sucrose crystallization in solutions under vacuum resulted in highly amorphous sucrose. Changes in the endothermic melting transition suggested reduced sucrose molecular mobility with increase in the sodium phosphate ratio. The addition of phosphate salts to sugar systems has several interesting features that merit its consideration in formulations to protect dehydrated labile biomaterials. In conclusion, our data suggest that sucrose and phosphate as additives seem to protect HSA during VFD better than lyophilized products and also maintain its stability in the VFD state during storage. PMID- 22313164 TI - Anti-D in pregnant women with the RHD(IVS3+1G>A)-associated DEL phenotype. AB - BACKGROUND: Pregnant women with the DEL phenotype appear to be D- by routine serology. Women with DEL phenotypes that show a partial D-like epitope loss may develop anti-D. It has been proposed that this alloantibody could have a deleterious effect with respect to hemolytic disease in the fetus and newborn. CASE REPORTS: Two pregnant women, one in Australia and one in Germany, were serotyped as D- and were sensitized to the D antigen. Noninvasive fetal RHD genotyping was performed to plan pregnancy management. RESULTS: In both cases the fetal RHD status could not be assigned due to the presence of a maternal DEL allele. This was suspected through detection of high RHD amplicon levels during quantitative polymerase chain reaction. For both cases extended molecular typing of the maternal genomic DNA revealed a RHD(IVS3+1G>A) allele. For case one, the D+ infant developed a mild hemolytic disease requiring phototherapy. In the second case a D- (or DEL) newborn was unaffected. CONCLUSION: Fetal genotyping from maternal plasma reveals RHD variants in pregnant women with anti-D. Fetuses and newborns of sensitized pregnant women carrying the RHD(IVS3+1G>A) allele are at risk of hemolytic disease. PMID- 22313166 TI - Ultrafast dynamics of the excited states of 1-(p-nitrophenyl)-2 (hydroxymethyl)pyrrolidine. AB - The dynamics of the excited states of 1-(p-nitrophenyl)-2 (hydroxymethyl)pyrrolidine (p-NPP) has been investigated using the subpicosecond transient absorption spectroscopic technique in different kinds of solvents. Following photoexcitation using 400 nm light, conformational relaxation via twisting of the nitro group, internal conversion (IC) and the intersystem crossing (ISC) processes have been established to be the three major relaxation pathways responsible for the ultrafast deactivation of the excited singlet (S(1)) state. Although the nitro-twisting process has been observed in all kinds of solvents, the relative probability of the occurrence of the other two processes has been found to be extremely sensitive to solvent polarity, because of alteration of the relative energies of the S(1) and the triplet (T(n)) states. In the solvents of lower polarity, the ISC is predominant over the IC process, because of near isoenergeticity of the S(1)(pipi*) and T(3)(npi*) states. On the other hand, in the solvents of very large polarity, the energy of the S(1)(pipi*) state becomes lower than those of both the T(3)(npi*) and T(2)(npi*/pipi*) states, but those of the T(1)(pipi*) state and the IC process to the ground electronic (S(0)) state are predominant over the ISC, and hence the triplet yield is nearly negligible. However, in the solvents of medium polarity, the S(1) and T(2) states become isoenergetic and the deactivation of the S(1) state is directed to both the IC and ISC channels. In the solvents of low and medium polarity, following the ISC process, the excited states undergo IC, vibrational relaxation, and solvation in the triplet manifold. On the other hand, following the IC process in the Franck-Condon region of the S(0) state, the vibrationally hot molecules with the twisted nitro group subsequently undergo the reverse nitro twisting process via dissipation of the excess vibrational energy to the solvent or vibrational cooling. PMID- 22313165 TI - Maternal heart rate patterns in the first and second stages of labor. AB - Objective. To analyze typical maternal heart rate (MHR) patterns in the first and second stages of labor. Design. Observational study. Setting. Tertiary care community hospital. Population. Normal term parturients with epidural anesthesia. Methods. Confirmed MHR and uterine activity were simultaneously recorded. The average MHR was analyzed 10 seconds before, as well as at the peak of, each contraction and/or pushing effort. Each woman contributed one datapoint at each time point to the analysis. Main outcome measure. Change in MHR during contractions. Results. First stage: 7.6+/-2.1 contractions per woman (n=18) were analyzed. Average MHR decreased during contractions: from 83+/-13 to 74+/-10bpm; p<0.001). In 56% (10/18) of the women, 'early' type decelerations were seen in at least 50% of contractions. Second stage: 3.5+/-1.5 contractions per woman. All women (n=15) showed MHR accelerations during every pushing effort (DeltaMHR: +35+/-13bpm; 88+/-14 to 123+/-17bpm; p<0.001). MHR was persistently >100bpm in three women (17%) in the first stage, and in four women (27%) in the second stage. Peak MHR >140bpm occurred during pushing in 20%. Conclusion. Decreases in MHR during contractions in the first stage of labor can mimic fetal heart rate (FHR) accelerations as well as early type decelerations. Thus, first stage tracings with a low baseline and early type decelerations may be maternal in origin and FHR should be independently confirmed in such tracings. Because second stage MHR accelerations generally show greater amplitude than FHR accelerations, tracings with repetitive accelerations during contractions (especially when Delta >20bpm) should be considered MHR until proven otherwise. PMID- 22313167 TI - High-nuclearity 3d-4f clusters as enhanced magnetic coolers and molecular magnets. AB - Four 52-metal-ion 3d-4f cluster complexes featuring a common core of Ln(42)M(10) (Ln = Gd(3+), Dy(3+); M = Co(2+/3+), Ni(2+)) were obtained through self-assembly of the metal ions templated by mixed anions (ClO(4)(-) and CO(3)(2-)). Magnetic studies revealed that the Gd(42)Co(10) and Gd(42)Ni(10) clusters exhibit the largest magnetocaloric effect (MCE) among any known 3d-4f complexes. Replacement of Gd(3+) ions with anisotropic Dy(3+) ions caused significant changes in the magnetic behavior of the clusters; both Dy(42)Co(10) and Dy(42)Ni(10) displayed slow relaxation of the magnetization. PMID- 22313168 TI - Risk assessment of airborne infectious diseases in aircraft cabins. AB - Passengers in an aircraft cabin can have different risks of infection from airborne infectious diseases such as influenza, severe acute respiratory syndrome (SARS), and tuberculosis (TB) because of the non-uniform airflow in an aircraft cabin. The current investigation presents a comprehensive approach to assessing the spatial and temporal distributions of airborne infection risk in an aircraft cabin. A case of influenza outbreak was evaluated in a 4-h flight in a twin aisle, fully occupied aircraft cabin with the index passenger seated at the center of the cabin. The approach considered the characteristics of the exhalation of the droplets carrying infectious agents from the index passenger, the dispersion of these droplets, and the inhalation of the droplets by susceptible passengers. Deterministic and probabilistic approaches were used to quantify the risks based on the amount of inhaled influenza virus RNA particles and quanta, respectively. The probabilistic approach indicated that the number of secondary infection cases can be reduced from 3 to 0 and 20 to 11, for influenza cases if N95 respirator masks are used by the passengers. The approach and methods developed can easily be implemented in other enclosed spaces such as buildings, trains, and buses to assess the infection risk. PRACTICAL IMPLICATIONS: Airborne infectious disease transmission could take place in enclosed environments such as buildings and transport vehicles. The infection risk is difficult to estimate, and very few mitigation methods are available. This study used a 4-h flight as an example in analyzing the infection risk from influenza and in mitigating the risk with an N95 mask. The results will be useful to the airline industry in providing necessary protection to passengers and crew, and the results can also be used for other enclosed spaces. PMID- 22313169 TI - Evaluation of the effectiveness of Face IT, a computer-based psychosocial intervention for disfigurement-related distress. AB - Some people who have a visible difference (disfigurement) experience psychosocial adjustment problems that can lead to social anxiety and isolation. The aim of this study was to assess the effectiveness of a new computerised CBT-based intervention (Face IT) in reducing anxiety and appearance-related distress for individuals with visible differences. Face IT was tested against a non intervention control group and standard CBT-based face-to-face delivery. Eighty three participants were assessed at four time points using the Hospital Anxiety and Depression Scales, Derriford Appearance Scale-24, Body Image Quality of Life Inventory and Fear of Negative Evaluation (FNE). The findings indicate a significant reduction in anxiety and appearance-related distress in both the Face IT intervention and the face-to-face condition. Similar findings were reported for depressive symptoms and FNE. Results at the three and six months follow-up demonstrate increased improvements in psychological functioning with both interventions. This new online psychosocial intervention has been found to be effective at reducing anxiety, depression and appearance concerns amongst individuals with disfigurements, whilst increasing positive adjustment. A remote access, computer-based intervention offers the potential to provide psychosocial support more easily and in a cost-effective manner to adults with appearance related distress. PMID- 22313170 TI - Long-term efficacy of single procedure remote magnetic catheter navigation for ablation of ischemic ventricular tachycardia: a retrospective study. AB - BACKGROUND: Remote magnetic navigation (RMN) aims to reduce some inherent limitations of manual radiofrequency (RF) ablation. However, data comparing the effectiveness of both methods are scarce. This study evaluated the acute and long term success of RMN guided versus manual RF ablation in patients with ischemic sustained ventricular tachycardia (sVT). METHODS: One hundred two consecutive patients (age 68 +/- 10 years, LVEF 32 +/- 12%, 88 men) with ischemic sVT were ablated with RMN (Stereotaxis; 49%) or manually (51%) using substrate and/or activation mapping (Carto) and open-irrigated-tip catheters. All received implantable defibrillators or loop recorders. Acute success was defined as noninducibility of any sVT at the end of the ablation procedure and long-term success as freedom from VT upon follow-up. RESULTS: There was no difference in the baseline characteristics between the groups. Three patients died in hospital. Acute success rate was similar for RMN and manual ablation (82% vs 71%, P = 0.246). RMN was associated with significantly shorter fluoroscopy time (13 +/- 12 minutes vs 32 +/- 17 minutes, P = 0.0001) and RF time (2337.59 +/- 1248.22 seconds vs 1589.95 +/- 1047.42 seconds, P = 0.049), although total procedure time was similar (157 +/- 40 minutes vs 148 +/- 50 minutes, P = 0.42). There was a nonsignificant trend toward better long-term success in RMN group: after a median of 13 (range 1-34) months, 63% in the RMN and 53% in the manual ablation group were free from VT recurrence (P = 0.206). CONCLUSION: RMN guided RF ablation of ischemic sustained VT is equally efficient compared with manual ablation in terms of acute and long-term success rate. These results are achieved with a significantly reduced fluoroscopy time and shorter RF time. PMID- 22313171 TI - Activity of isoflavones and berberine on vasomotor symptoms and lipid profile in menopausal women. AB - The aim of this study was to evaluate the efficacy of a food supplement combination based on isoflavones and berberine (ISB) in the treatment of menopausal symptoms and dyslipidaemia. Isoflavones are extracted from soy and absorbed in the body after being activated by lactobacillus. Berberine, extracted from the plant Berberis aristata, lowers plasma cholesterol and triglycerides (TG) by increasing low-density lipoprotein (LDL) receptors and reducing hepatic synthesis of TG. One hundred twenty women with a mean age of 54.8 +/- 0.6 years were enrolled and randomized to treatment with ISB (estromineral lipid [EL] = 60 cases) or calcium and vitamin D(3) (CaD = 60 cases). Menopausal symptoms, plasma cholesterol, and TG were evaluated at baseline, and after 4 and 12 weeks. EL treatment significantly lowered plasma total cholesterol (-13.5% +/- 0.7 vs -0.2% +/- 0.5), LDL cholesterol (-12.4% +/- 1.5 vs + 0.8 % +/- 0.7) and TG (-18.9% +/- 2.5 vs -1.3% +/- 1.2) and improved menopausal symptoms compared with CaD treatment. Safety parameters were unchanged during the study. The combination of berberine and isoflavones was effective in lowering cardiovascular (CV) risk factors in menopausal women with moderate dyslipidaemia and in improving their quality of life. PMID- 22313172 TI - Saxagliptin plus metformin combination in patients with type 2 diabetes and renal impairment. AB - INTRODUCTION: A metformin plus saxagliptin fixed-dose combination is now proposed to clinicians. Furthermore, saxagliptin's license was recently extended to include diabetic patients with moderate or severe renal impairment (RI). However, metformin is still contraindicated in patients with RI. AREAS COVERED: This review analyses the pro and contra of using a combination of saxagliptin and metformin (separately or as a fixed-dose combination) in type 2 diabetic patients with moderate or severe RI. An extensive literature search of all pharmacokinetic data and efficacy/safety profile of metformin and saxagliptin in subjects with RI was performed. EXPERT OPINION: Since both metformin and saxagliptin are excreted via the kidney, dose adjustment is required in case of moderate-to-severe RI (half dose of saxagliptin). However, major discrepancies exist between guidelines (metformin excluded in case of RI because of the risk of lactic acidosis) and real life (metformin widely prescribed in patients with some degree of RI). Physicians should weigh the benefit/risk ratio carefully before deciding to prescribe or withdraw the combination metformin plus saxagliptin in patients with stable RI. A redefinition of contraindications to metformin will enable more physicians to prescribe within guidelines and to administer saxagliptin combined with metformin in more patients who clearly may benefit from this combination. PMID- 22313173 TI - Reconnecting cognition in the lab and cognition in real life: The role of compensatory social and motivational factors in explaining how cognition ages in the wild. AB - The papers in this Special Issue compellingly show that older adults' everyday cognitive life is governed not by the decline in elementary cognitive processes as measured in the lab, but by a multitude of compensatory mechanisms, most of which are of the social/motivational variety. Much of this compensatory behavior can be elicited with no or only little experimental prodding, underscoring the self-organizing or self-initiated nature of this type of behavior, even in advanced old age. We suggest that the study of compensation and the orchestration of cognitive, social, and motivational compensatory mechanisms in effective and healthy aging provides a meaningful challenge to traditional ways of examining developmental changes in cognitive performance. PMID- 22313174 TI - Cognitive function, physical activity, and aging: possible biological links and implications for multimodal interventions. AB - Increasing evidence shows the positive effect of physical activity (PA) on maintaining cognitive function. Both processes seem intrinsically linked to each other. The most likely mechanism is a reciprocal stimulation of neuroplasticity. Based on extensive experimental work on animals and humans, the concept of an enriched environment, including PA and challenging cognitive tasks, has provided the basis to systematically assess possible interventions for successful aging. I will use recent findings on brain mechanisms associated with PA and its effects on higher cognitive function at a systems and molecular level to demonstrate the need to design effective interventions. Such interventions should be designed to take advantage of the presumed compensatory mechanisms of elderly individuals, thereby limiting functional decline in higher cognitive performance in aging people. My review of the most recent relevant publications concerning this topic supports the notion that it is a promising approach to provide cognitive training and PA in conjunction, since the combination may generate synergistic beneficial changes than either one individually. Multimodal training programs should therefore be tested. However, at present there is insufficient evidence to conclude that multimodal interventions are superior to isolated cognitive or physical exercise interventions, since major studies addressing this topic are lacking. These studies are needed to conclusively prove that both strategies will positively interact when used in combined interventions. Finally the use of modern technology for these interventions will be discussed. PMID- 22313175 TI - Potential for abiotic reduction of pesticides in Prairie pothole porewaters. AB - Prairie pothole lakes (PPLs) are critical hydrological and ecological components of central North America and represent one of the largest inland wetland systems on Earth. These lakes are located within an agricultural region, and many of them are subject to nonpoint-source pesticide pollution. Limited attention, however, has been paid to understanding the impact of PPL water chemistry on the fate and persistence of pesticides. In this study, the abiotic reductive transformation of seven dinitroaniline pesticides was investigated in PPL sediment porewaters containing naturally abundant levels of reduced sulfur species (i.e., bisulfide (HS(-)) and polysulfides (S(n)(2-))) and dissolved organic matter (DOM). Target dinitroanilines underwent rapid degradation in PPL porewaters and were transformed into corresponding amine products. While the largest fraction of the transformation could be attributed to reduced sulfur species, experimental evidence suggested that other reactive entities in PPL porewaters, such as DOM and mineral phases, might also affect the reaction rates of dinitroanilines. Results from this study highlight the importance of reductive transformation as an abiotic natural attenuation pathway for pesticides entering the PPL sedimentary environment. PMID- 22313176 TI - Synthesis and characterization of 7,8,15,16-tetraazaterrylene. AB - A facile three-step synthesis of 7,8,15,16-tetraazaterrylene (TAT) from phenalene 1,3-dione, with potential application in organic electronics, is reported. Single crystal structure analysis shows one-dimensional columnar stacks with an interplanar distance of 3.352 A. PMID- 22313177 TI - Maternal and neonatal outcomes of grand multiparas over two decades in Mali. AB - OBJECTIVE: To analyze the association between grand multiparity and maternal and neonatal morbidity and mortality. DESIGN: Retrospective cross-sectional study. SETTING: Point G National Hospital, a tertiary care hospital in Bamako, Mali. POPULATION: All singleton births from 1985 to 2003. METHODS: Cross-sectional study of 13 340 singleton births at a tertiary care hospital in Mali (1985-2003) compared outcomes between 3617 grand multiparas (para >=5) and 9723 pauciparas (para 1-4). Odds ratios (OR) were adjusted for maternal age, prenatal care utilization, socioeconomic status, and region of origin. MAIN OUTCOME MEASURES: Maternal mortality, perinatal mortality, placental abnormalities (previa and abruption), uterine rupture, postpartum infection, postpartum hemorrhage, eclampsia, cesarean delivery, mean birthweight, low birthweight, high birthweight. RESULTS: Grand multiparas were older, poorer, and less likely to have accessed prenatal care. Grand multiparas had a lower adjusted odds of maternal death (adjusted OR, 0.66; 95%CI, 0.45-0.97), but higher adjusted odds of perinatal death (adjusted OR, 1.33; 95%CI, 1.12-1.59), placental abnormalities (adjusted OR, 1.57; 95%CI, 1.21-2.05), and high birthweight (adjusted OR, 1.42; 95%CI, 1.05-1.92). CONCLUSIONS: The healthy person effect may explain grand multiparas' lower odds of maternal death. Reducing grand multiparity and improving grand multiparas' access to prenatal care may improve population-level perinatal outcomes. PMID- 22313178 TI - Teaching suffering: the testimonial-commentary method. AB - Attempts to define professionalism and humanism suggest that qualities such as compliance to values, patient access, doctor-patient relationship, demeanor, professional management, personal awareness, and motivation are prominent thematic components. In this communication, we present a method for instruction in the values of humanism that may help to overcome the "curricular inertia that plagues medical education." Our approach is structured around a technique of testimonial-commentary as a novel approach to teaching humanism that does not rely upon the traditional role-modeling format. To develop effective medical school curricula for teaching humanism, we cannot rely upon the textbooks of normal and abnormal human anatomy and physiology. We must delve into the "unscientific" realms of human identity ranging from sensuality to brutality: self-preservation to sacrifice. Underneath it all, we must acknowledge that there are the ties that bind us together as people. The Seminar on Human Suffering challenges medical school educators to work with the community at large to insure that physicians will be able to serve those that seek their counsel. PMID- 22313179 TI - Copper(II) complexes of salicylic acid combining superoxide dismutase mimetic properties with DNA binding and cleaving capabilities display promising chemotherapeutic potential with fast acting in vitro cytotoxicity against cisplatin sensitive and resistant cancer cell lines. AB - The complexes [Cu(salH)(2)(H(2)O)] (1), [Cu(dipsH)(2)(H(2)O)] (2), {Cu(3 MeOsal)(H(2)O)(0.75)}(n) (3), [Cu(dipsH)(2)(BZDH)(2)] (4), [Cu(dipsH)(2)(2 MeOHBZDH)(2)].EtOH (5), [Cu(sal)(phen)] (6), [Cu(dips)(phen)].H(2)O (7), and [Cu(3-MeOsal)(phen)].H(2)O (8) (salH(2) = salicylic acid; dipsH(2) = 3,5 diisopropylsalicylic acid; 3-MeOsalH(2) = 3-methoxysalicylic acid; BZDH = benzimidazole; 2-MeOHBZDH = 2 methanolbenzimidazole and phen =1,10 phenanthroline) were prepared and characterized. Structures of 4, 5, and 8 were determined by X-ray crystallography. Compounds 1-8 are potent superoxide dismutase mimetics, and they are inactive as inhibitors of COX-2 activity. Compounds 1, 4, and 5 exhibit moderate inhibition of COX-1. Complexes 6-8 display rapid micromolar cytotoxicity against cisplatin sensitive (breast (MCF-7), prostate (DU145), and colon (HT29)) and cisplatin resistant (ovarian (SK-OV-3)) cell lines compared to 1-5, and they exhibit potent in vitro DNA binding and cleavage capabilities. PMID- 22313180 TI - Mollusk shell nacre ultrastructure correlates with environmental temperature and pressure. AB - Nacre, or mother-of-pearl, the tough, iridescent biomineral lining the inner side of some mollusk shells, has alternating biogenic aragonite (calcium carbonate, CaCO(3)) tablet layers and organic sheets. Nacre has been common in the shells of mollusks since the Ordovician (450 million years ago) and is abundant and well preserved in the fossil record, e.g., in ammonites. Therefore, if any measurable physical aspect of the nacre structure was correlated with environmental temperatures, one could obtain a structural paleothermometer of ancient climates. Using X-ray absorption near-edge structure (XANES) spectroscopy, Photoelectron emission spectromicroscopy (PEEM), and X-ray linear dichroism we acquired polarization-dependent imaging contrast (PIC) maps of pristine nacre in cross section. The new PIC-map data reveal that the nacre ultrastructure (nacre tablet width, thickness, and angle spread) is species-specific in at least eight mollusk species from completely different environments: Nautilus pompilius, Haliotis iris, Haliotis rufescens, Bathymodiolus azoricus, Atrina rigida, Lasmigona complanata, Pinctada margaritifera, and Mytilus californianus. Nacre species specificity is interpreted as a result of adaptation to diverging environments. We found strong correlation between nacre crystal misorientations and environmental temperature, further supported by secondary ion mass spectrometry measurements of in situ delta(18)O in the nacre of one shell. This has far reaching implications: nacre texture may be used as a paleothermometer of ancient climate, spanning 450 million years of Earth's history. PMID- 22313181 TI - Using the Omaha System as a framework to demonstrate the value of nurse managed wellness center services for vulnerable populations. AB - Nurse managed wellness centers (NMWCs) are academic service settings where baccalaureate nursing students gain rich community health clinical experience while providing valuable wellness services to a vulnerable population. The Omaha System provides a framework for generating meaningful data that is essential for describing the value of NMWCs. A retrospective study of Omaha System assessments from 9 NMWCs provides descriptive data about the characteristics of the patient population and patient outcomes in relationship to knowledge, behavior, and status. Patients showed significant improvement for the overall sample and for 6 important health problems. These findings support anecdotal data about the value of NMWC for a vulnerable population. Research for this article was funded in part by a grant from HighMark. PMID- 22313182 TI - The effect of a community garden on HgA1c in diabetics of Marshallese descent. AB - A mixed-convergent parallell designed intervention study was created to learn whether a community garden could provide improved diabetes control for members of a Midwest community of immigrants from the Marshall Islands. Qualitative data gathered through field observations on cultural norms and beliefs, food perceptions, and barriers to health care corrobrorated data gained at medical appointments for diabetes follow-up. Marshallese clients from a local community health center were recruited to participate in a community garden. Persons who participated in a community garden had significant reduction in their HgA1c postintervention, compared to persons who did not participate actively. PMID- 22313183 TI - Differences in home-based family caregiving appraisal for caregivers of the elderly in rural and urban Japanese communities. AB - This quantitative study aimed to determine the differences between rural and urban residencies related to home-based appraisal (including care burden and positive appraisal) for Japanese primary family caregivers of the elderly with extensive care needs. The study examined a sample of 196 caregivers (106 rural, 90 urban), and stepwise multiple regression analysis was performed. Resident location was significantly associated with care burden, and each factor associated with the appraisal, especially care burden, differed between rural and urban areas. The social and physical environment is thus a necessary consideration to support family caregivers and the elderly requiring home-based care. PMID- 22313184 TI - The Weighty Matter intervention: a family-centered way to tackle an overweight childhood. AB - The complexity of childhood overweight and obesity requires that researchers continue to investigate potential solutions. We developed "The Weighty Matter" intervention to prevent obesity in mildly overweight 4- and 6-year-old children. This article describes the intervention protocol, the health habits of families (n=86), and the effect of the intervention on children's weight for height, parents' body mass indices, and family health habits after a 12-month follow-up. Positive changes were seen in families' health habits, although the results did not reach statistical significance. As a result of this study, a new and practical method was developed to focus on the issue of family health habits. PMID- 22313185 TI - Linking classroom learning to the community through service learning. AB - Service learning is valued as a means of providing education to students and service to the community. The purpose of this article is to describe the incorporation of service learning in an undergraduate baccalaureate level Gerontology nursing course. Details of the service learning experience, community agency partnership, the students' reflections, evaluations from both the students and community agency staff, and faculty challenges are presented. This information may be useful to others who are considering service learning as a strategy for educating students while providing service to the community. PMID- 22313187 TI - Pyridine*BrF3, the missing link for clean fluorinations of aromatic derivatives. AB - This work demonstrates the unique features of the never used before Py*BrF(3) complex in the field of aromatic organic fluorinations. The main disadvantage of the noncomplexed BrF(3) is the fact that usually, in addition to the desired fluorination, a parallel electrophilic aromatic bromination takes place as well. Use of the Py*BrF(3) complex reduces this electrophilic bromination, which is observed with most reagents based on fluorine and bromine [BrF]. PMID- 22313188 TI - Effect of crown ethers on the ground and excited state reactivity of samarium diiodide in acetonitrile. AB - Electron transfer from the ground and excited states of Sm[15-crown-5](2)I(2) complex to a series of electron acceptors (benzaldehyde, acetophenone, benzophenone, nitrobenzene, benzyl bromide, benzyl chloride, 1-iodohexane, and 1,4-dinitrobenzene) was investigated in acetonitrile. Electron transfer from the ground state of the Sm(II)-crown system to aldehydes and ketones has a significant inner sphere component indicating that the oxophilic nature of Sm(II) prevails in the system even in the presence of bulky ligands such as 15-crown-5 ether. Activation parameters for the ground state electron transfer were determined, and the values were consistent with the proposed mechanistic models. Since crown ethers stabilize the photoexcited states of Sm(II), the photochemistry of Sm[15-crown-5](2)I(2) system in solution state has been investigated in detail. The results suggest that photoinduced electron transfer from Sm(II)-crown systems to a wide variety of substrates is feasible with rate constant values as high as 10(7) M(-1) s(-1). The results described herein imply that the present difficulty of manipulating the extremely reactive excited state of Sm(II) in solution phase can be overcome through stabilizing the excited state of the divalent metal ion by careful design of the ligand systems. PMID- 22313189 TI - Carbon nanotube compared with carbon black: effects on bacterial survival against grazing by ciliates and antimicrobial treatments. AB - The ingestion and digestion of Escherichia coli by the ciliated protozoan, Tetrahymena thermophila, was investigated after an initial exposure to either water-soluble single-walled carbon nanotubes (SWNT) or to carbon black (CB). Both SWNT and CB were internalised and visible in food vacuoles of ciliates. When presented with E. coli expressing green-fluorescent protein (GFP), these ciliates internalised bacteria as well. However, ciliates that had first internalised SWNT but not CB subsequently externalised or egested vesicle-like structures with fluorescent bacteria inside. These egested bacteria were viable and less susceptible than planktonic E. coli to killing either by the antibiotic, chloramphenicol or the disinfectant, glutaraldehyde. These results suggest that SWNT can alter the intracellular trafficking of vesicles within ciliates, leading to bacterial prey being packaged externally and protected for a time from environmental killing, which could have implications for sewage treatment and for public health. PMID- 22313190 TI - Identification of platinum and palladium particles emitted from vehicles and dispersed into the surface environment. AB - Platinum, palladium, and rhodium are emitted from vehicle catalytic converters. Until now, the form of precious metal particles in road dust and urban waste has not been identified. This study has located, imaged, and analyzed these particles in road dust and gully waste. Two fragments of catalytic converter have been observed in road dust. They are 40-80 MUm in size and covered in many minute particles (<0.3 MUm) of either platinum with minor rhodium or palladium. One fragment identified in gully sediment is smaller, 25 MUm in diameter, hosting only one attached particle of palladium with minor rhodium. As fragments are washed off roads they begin to disintegrate and the precious metals become detached. Also precious metal-bearing particles have been located in incinerated sewage ash including a 20 MUm diameter cluster of <3 MUm sized platinum particles that may be the remains of a catalytic converter fragment that has survived incineration. The form of these precious metal-bearing particles described here reveals that as they are dispersed from roads they are likely to be present predominantly as two particle sizes. Either they are attached to larger fragments of catalytic converter or they are released as individual detached tiny <0.3 MUm to nanoparticle sizes. PMID- 22313191 TI - Iodine bonding stabilizes iodomethane in MIDAS pesticide. Theoretical study of intermolecular interactions between iodomethane and chloropicrin. AB - The results are reported of a theoretical study of iodomethane (H(3)C-I, 1) and chloropicrin (Cl(3)C-NO(2), 2), of the heterodimers 3-6 formed by aggregation of 1 and 2, and of their addition products 7 and 8 and their possible fragmentation reactions to 9-18. Mixtures of iodomethane and chloropicrin are not expected to show chemistry resulting from their reactions with each other. The structures and stabilities are discussed of the iodine-bonded molecular aggregates (IBMA) 3 and 4 and of the hydrogen- and iodine-bonded molecular aggregates (IHBMA) 5 and 6. The mixed aggregates 3-5 are bound on the free enthalpy surface relative to the homodimers of 1 and 2, and the IBMA structures 3 and 4 are most stable. This result suggests that the mixture of chloropicrin and iodomethane in the pesticide Midas is a good choice to reduce the volatility of iodomethane because of thermodynamically stabilizing iodine bonding. PMID- 22313192 TI - Internet-delivered behavioral intervention to increase physical activity in persons with multiple sclerosis: sustainability and secondary outcomes. AB - Physical activity is associated with many benefits, but persons with multiple sclerosis (MS) are less physically active than the general population. There is a critical need for research on methods of increasing and sustaining the physical activity levels of this population. This randomized controlled trial examined the efficacy of an Internet-delivered and theory-based behavioral intervention that was supplemented with video coaching for increasing and sustaining physical activity over time in persons with MS. Physically inactive, ambulatory persons with MS (N = 45) were randomly assigned to intervention (n = 22) or control (n = 23) conditions and completed a battery of questionnaires before, after, and three months after a 12-week intervention period. Data analyses were conducted in PASW 18.0. Partial eta squared ([Formula: see text]) effect size indicated that there was a large, statistically significant condition-by-time interaction on physical activity ([Formula: see text]). Cohen's d effect sizes indicated that the intervention group had a large increase in physical activity after the 12-week trial (d = .98) that was sustained over a three-month follow-up (d = .79). The current study supports the efficacy of a behavioral intervention for increasing and sustaining physical activity in a sample of persons with MS. PMID- 22313194 TI - Three-year outcomes of the RESILIENT trial: are they enough to support a primary stenting policy? PMID- 22313193 TI - Nitinol stent implantation vs. balloon angioplasty for lesions in the superficial femoral and proximal popliteal arteries of patients with claudication: three-year follow-up from the RESILIENT randomized trial. AB - PURPOSE: To evaluate longer outcomes of primary nitinol stenting for the treatment of femoropopliteal lesions up to 15 cm long after these stents were found to have superior short-term patency vs. balloon angioplasty. METHODS: Two hundred and six patients (143 men; mean age 67 years) with intermittent claudication due to superficial femoral and proximal popliteal artery lesions were randomized (2:1) to treatment with nitinol stents or balloon angioplasty at 24 US and European centers and followed for 3 years. In that time, 15 patients died, 20 withdrew consent, and 10 were lost to follow-up, leaving 161 (78.2%) patients for 36-month assessment. RESULTS: The 12-month freedom from target lesion revascularization (TLR) was 87.3% for the stent group vs. 45.2% for the angioplasty group (p<0.0001). At 3 years, there was no difference in survival (90.0% vs. 91.7%, p=0.71) or major adverse events (75.2% vs. 75.2%, p=0.98) between the stent and angioplasty groups. Duplex ultrasound was not mandated after the first year, so stent patency could not be ascertained beyond 1 year, but freedom from TLR at 3 years was significantly better in the stent group (75.5% vs. 41.8%, p<0.0001), as was clinical success (63.2% vs. 17.9%, p<0.0001). At 18 months, a 4.1% (12/291) stent fracture rate was documented. CONCLUSION: In this multicenter trial, primary implantation of a nitinol stent for moderate length lesions in the femoropopliteal segment of patients with claudication was associated with better long-term results vs. balloon angioplasty alone. PMID- 22313195 TI - Sirolimus-eluting stents for the treatment of infrapopliteal arteries in chronic limb ischemia: long-term clinical and angiographic follow-up. AB - PURPOSE: To present the 5-year angiographic and clinical results of a retrospective registry assessing the performance of sirolimus-eluting stents (SES) in the treatment of infrapopliteal atherosclerotic disease. METHODS: From 2004 to 2009, 158 patients (95 men; mean age 71.9 years) with chronic lower limb ischemia (Rutherford categories 3-6) underwent primary SES placement in focal infrapopliteal lesions. The angiographic endpoint was patency, defined as freedom from in-stent stenosis (ISS) >50%. Clinical endpoints were death, amputation, and bypass surgery. Results were correlated with patient and lesion characteristics and cumulative outcomes were assessed with Kaplan-Meier analysis. RESULTS: Technical success was achieved in all cases. The primary patency rates were 97.0% after 6 months, 87.0% after 12 months, and 83.8% at 60 months. In-stent stenosis was predominantly observed in the first year after stent placement. Female gender was associated with a higher rate of ISS. During clinical follow-up of 144 (91%) patients over a mean 31.1+/-20.3 months, there were 27 (18.8%) deaths, 4 (2.8%) amputations, and no bypass surgery. Clinical status improved in 92% of the patients with critical limb ischemia (CLI) and 77% of the patients suffering from claudication (p=0.022). CONCLUSION: Treatment of focal infrapopliteal lesions with SES showed encouraging long-term angiographic results in this registry. Clinical improvement was evident, but more pronounced in CLI patients than in patients suffering from claudication. Further studies are needed to evaluate the potential clinical benefit of SES as compared to balloon angioplasty or bare metal stents in the treatment of infrapopliteal lesions. PMID- 22313196 TI - Prime time for infrapopliteal drug-eluting stents? PMID- 22313197 TI - Retrograde recanalization technique for use after failed antegrade angioplasty in chronic femoral artery occlusions. AB - PURPOSE: To describe a technique to approach chronic total occlusions (CTOs) of the superficial femoral artery (SFA) after failed antegrade recanalization as an alternative to a conventional transpopliteal approach. METHODS: A retrospective analysis was undertaken of 50 patients (37 men; mean age 71 years) who underwent retrograde recanalization via a distal SFA access after failed antegrade recanalization of SFA CTOs that were not beyond the adductor canal. Antegrade recanalization failed due to flush SFA occlusion, occluded stents, wire perforation, and re-entry failure. Retrograde SFA access required introduction of a 7- to 15-cm, 21-G needle distal to the occlusion. A 0.018-inch guidewire was inserted through the needle followed by a 4- or 6-F, 10-cm sheath or dedicated support catheter only. All retrograde SFA punctures were performed with the patient in the supine position. Once retrograde passage of the occlusion was successful, oftentimes requiring a "double-balloon" technique to disrupt the dissection membrane with abutting balloons delivered from both access sites, balloon angioplasty and/or stenting could be performed from either direction. RESULTS: Retrograde puncture of the distal SFA was successful in all cases. Retrograde recanalization involved insertion of a 6-F sheath in 3 (6%) cases, a 4 F sheath in 32 (64%), and a sheathless approach in 15 (30%). The "double-balloon" technique was necessary to achieve guidewire passage in 12 cases. Recanalization was successful in 48 (96%) cases. Hemostasis time at the distal puncture site was 9.2 minutes (range 3-30). Perioperative complications included 4 pseudoaneurysms (2 groins, 2 distal), 1 peripheral embolization, and 1 small arteriovenous fistula at the distal puncture site. CONCLUSION: For failure of antegrade recanalization of SFA occlusions, the retrograde SFA puncture distal to the adductor canal with the patient remaining supine is a safe and successful technique that represents a convenient alternative to the conventional transpopliteal approach. PMID- 22313198 TI - Stent puncture for recanalization of occluded superficial femoral artery stents. AB - PURPOSE: To describe a technique to recanalize occluded superficial femoral artery (SFA) stents without inflow or outflow in patients with proximal SFA obstruction. TECHNIQUE: After a failed attempt to engage an occluded stent through an antegrade femoral approach, a distal retrograde puncture of the proximal part of the stent was performed. After subintimal rendezvous with a catheter advanced from the antegrade access, in-stent angioplasty can be performed to recanalize the stent and SFA. CONCLUSION: Direct retrograde puncture of an occluded stent may be considered an approach to recanalization in patients with stent occlusion and no inflow or outflow. PMID- 22313199 TI - Endovascular popliteal thrombectomy using the self-expanding, retrievable Solitaire recanalization device. AB - PURPOSE: To present an initial peripheral application of the self-expanding, detachable, fully-retrievable Solitaire FR Recanalization Device for endovascular thrombectomy in the lower leg of a patient with acute peripheral limb ischemia. CASE REPORT: A 79-year-old woman with a long history of peripheral arterial occlusive disease and a femoropopliteal bypass graft presented with sudden grade IIb ischemia of the left lower leg. Conventional antegrade angiography identified total thrombotic occlusion of the tibioperoneal trunk below the distal femoropopliteal bypass anastomosis; the bypass itself was not occluded. When suction thrombectomy was unsuccessful, a 4*20-mm self-expanding, retrievable Solitaire stent was deployed. The thrombus was retrieved, with immediate recanalization of the tibioperoneal trunk and no sequela. Clinical signs of ischemia resolved, and after 6 months of follow-up, no reocclusion had occurred. CONCLUSION: Developed as a tool to retrieve clots causing acute ischemic stroke, the Solitaire FR Recanalization Device may also have a place in treating patients with acute below-the-knee thrombotic arterial occlusion in whom suction thrombectomy had failed. The Solitaire stent may be an additional endovascular option that can result in successful treatment of acute limb ischemia and avoid more expensive surgical procedures in selected cases. PMID- 22313200 TI - Mechanisms of symptomatic spinal cord ischemia after TEVAR: insights from the European Registry of Endovascular Aortic Repair Complications (EuREC). AB - PURPOSE: To test the hypothesis that simultaneous closure of at least 2 independent vascular territories supplying the spinal cord and/or prolonged hypotension may be associated with symptomatic spinal cord ischemia (SCI) after thoracic endovascular aortic repair (TEVAR). METHODS: A pattern matching algorithm was used to develop a risk model for symptomatic SCI using a prospective 63-patient single-center cohort to test the positive predictive value (PPV) of prolonged intraoperative hypotension and/or simultaneous closure of at least 2 of 4 the vascular territories supplying the spinal cord (left subclavian, intercostal, lumbar, and hypogastric arteries). This risk model was then applied to data extracted from the multicenter European Registry on Endovascular Aortic Repair Complications (EuREC). Between 2002 and 2010, the 19 centers participating in EuREC reported 38 (1.7%) cases of symptomatic spinal cord ischemia among the 2235 patients in the database. RESULTS: In the single-center cohort, direct correlations were seen between the occurrence of symptomatic SCI and both prolonged intraoperative hypotension (PPV 1.00, 95% CI 0.22 to 1.00, p=0.04) and simultaneous closure of at least 2 independent spinal cord vascular territories (PPV 0.67, 95% CI 0.24 to 0.91, p=0.005). Previous closure of a single vascular territory was not associated with an increased risk of symptomatic spinal cord ischemia (PPV 0.07, 95% CI 0.01 to 0.16, p=0.56). The combination of prolonged hypotension and simultaneous closure of at least 2 territories exhibited the strongest association (PPV 0.75, 95% CI 0.38 to 0.75, p<0.0001). Applying the model to the entire EuREC cohort found an almost perfect agreement between the predicted and observed risk factors (kappa 0.77, 95% CI 0.65 to 0.90). CONCLUSION: Extensive coverage of intercostal arteries alone by a thoracic stent graft is not associated with symptomatic SCI; however, simultaneous closure of at least 2 vascular territories supplying the spinal cord is highly relevant, especially in combination with prolonged intraoperative hypotension. As such, these results further emphasize the need to preserve the left subclavian artery during TEVAR. PMID- 22313201 TI - Endovascular stenting vs. extrathoracic surgical bypass for symptomatic subclavian steal syndrome. AB - PURPOSE: To analyze the immediate and long-term outcomes of endovascular stenting vs. extrathoracic surgical bypass for subclavian steal syndrome. METHODS: From 1989 to 2010, 252 consecutive patients (173 men; mean age 62 years) with vertebrobasilar and upper extremity symptoms of subclavian steal were treated with balloon-expandable stents (n=148) or extrathoracic surgical bypasses (n=104: 71 axilloaxillary and 33 carotid-subclavian) using polytetrafluoroethylene grafts. RESULTS: The technical success rate was 97.3% in the stent group vs. 99.0% for the bypass group (p=0.605). There was no perioperative mortality or any permanent neurological deficit in either group. The overall perioperative complication rate was 6.1% in the stent group vs. 9.6% in the bypass group (p=0.295). The 10-year target vessel revascularization rate was 46.6% for stenting vs. 5.8% for bypass (p<0.001). The cumulative primary patency rates at 1, 3, 5, and 10 years were 91%, 78%, 67%, and 49% for the stent group vs. 99%, 97%, 95%, and 89% for the bypass group (p<0.001). The cumulative secondary patency rates were 95%, 91%, 86%, and 64%, respectively, for the stent group vs. 99%, 99%, 98%, and 94% for the bypass group (p=0.001). No difference was detected in overall survival curves between the groups (p=0.527). CONCLUSION: Both endovascular stenting and extrathoracic surgical bypass are safe and effective treatments for subclavian steal syndrome in the short and medium term; however, extrathoracic surgical bypasses are more durable in the long term. PMID- 22313202 TI - Endovascular management of pseudoaneurysm formation in the ascending aorta following lung transplantation. AB - PURPOSE: To demonstrate the role of endovascular approaches to the ascending aorta in the post-transplant context. CASE REPORTS: Three patients (2 women and 1 man aged 52, 68, and 43 years, respectively) developed pseudoaneurysm of the ascending aorta following thoracic organ transplantation. Due to the prohibitive risk of open surgery in each case, an endovascular repair of the ascending aorta was performed, with implantation of 1 to 3 stent-grafts to span the lesions. Follow-up imaging demonstrated complete exclusion of the pseudoaneurysms, with excellent outcomes at 4 months, 6 months, and 3 years. CONCLUSION: Stent-grafting of the ascending aorta represents a viable approach to pseudoaneurysm in the post transplant setting. PMID- 22313203 TI - Early results from a Canadian multicenter prospective registry of the Endurant stent graft for endovascular treatment of abdominal aortic aneurysms. AB - PURPOSE: To report the early results of a multicenter registry of endovascular aneurysm repair (EVAR) using the Endurant stent-graft. METHODS: Patients having elective treatment of infrarenal abdominal aortic aneurysm (AAA) with the Endurant stent-graft at 3 Canadian centers were enrolled in a prospective registry between September 2008 and January 2010. In the 16-month period, 111 patients (90 men; mean age 75 years, range 53-93) were registered. Thirty-seven (33.3%) patients had challenging anatomy: short proximal aortic necks (n=17), large diameter (>28 mm) aortic necks (n=4), angulated (>60 degrees ) necks (n=3), and small (<15 mm) external iliac arteries (n=21). Outcomes evaluated included survival, endoleak, aneurysm expansion >5 mm, secondary intervention, stent-graft migration, and graft thrombosis. RESULTS: The overall technical success rate was 100%. Nineteen (17.1%) patients experienced perioperative complications. After a mean follow-up of 6 months (range 0.1-16), mortality in the series was 4.5%: 1 perioperative death (multisystem organ failure) and 4 (3.6%) late deaths (3 cardiac, 1 cancer). Clinical and imaging follow-up past the perioperative period were available in 107 (96.4%) and 99 (89.2%) patients, respectively. Among the latter, 9 (9.1%) had a type II endoleak on the first scan; 4 resolved spontaneously. Three (3.0%) patients developed graft limb thrombosis in follow up; one required an intervention. There was no graft migration, aneurysm expansion, secondary intervention for endoleak, aneurysm rupture, or conversion. CONCLUSION: Early results from this prospective multicenter registry indicate that the Endurant stent-graft is a safe option for elective EVAR in selected AAA patients. Longer follow-up is required to determine the durability of these outcomes. PMID- 22313204 TI - Endurant continues to impress, but long-term data are still needed for success. PMID- 22313205 TI - Three-dimensional electromagnetic navigation vs. fluoroscopy for endovascular aneurysm repair: a prospective feasibility study in patients. AB - PURPOSE: To evaluate the in vivo feasibility of a 3-dimensional (3D) electromagnetic (EM) navigation system with electromagnetically-tracked catheters in endovascular aneurysm repair (EVAR). METHODS: The pilot study included 17 patients undergoing EVAR with a bifurcated stent-graft. Ten patients were assigned to the control group, in which a standard EVAR procedure was used. The remaining 7 patients (intervention group) underwent an EVAR procedure during which a cone-beam computed tomography image was acquired after implantation of the main stent-graft. The 3D image was presented on the navigation screen. From the contralateral side, the tip of an electromagnetically-tracked catheter was visualized in the 3D image and positioned in front of the contralateral cuff in the main stent-graft. A guidewire was inserted through the catheter and blindly placed into the stent-graft. The placement of the guidewire was verified by fluoroscopy before the catheter was pushed over the guidewire. If the guidewire was incorrectly placed outside the stent-graft, the procedure was repeated. Successful placement of the guidewire had to be achieved within a 15-minute time limit. RESULTS: Within 15 minutes, the guidewire was placed correctly inside the stent-graft in 6 of 7 patients in the intervention group and in 8 of 10 patients in the control group. In the intervention group, fewer attempts were needed to insert the guidewire correctly. CONCLUSION: A 3D EM navigation system, used in conjunction with fluoroscopy and angiography, has the potential to provide more spatial information and reduce the use of radiation and contrast during endovascular interventions. This pilot study showed that 3D EM navigation is feasible in patients undergoing EVAR. However, a larger study must be performed to determine if 3D EM navigation is better than the existing practice for these patients. PMID- 22313206 TI - Stent-graft limb deployment in the external iliac artery increases the risk of limb occlusion following endovascular AAA repair. AB - PURPOSE: To assess whether deployment of an endograft limb in the external iliac artery (EIA) increases the rate of limb occlusion following endovascular aneurysm repair (EVAR). METHODS: Interrogation of a prospectively maintained database identified 661 patients (596 men; median age 73 years, range 37-93) with infrarenal abdominal aortic aneurysm who underwent EVAR between 1996 and 2010 using Zenith stent-grafts predominately. Of these, 567 patients [56 (9.9%) women] had both endograft limbs deployed in the CIA (1203 limbs at risk), while 94 patients [9 (9.6%) women] had at least 1 limb in the EIA (22 bilateral; 116 limbs at risk). An adjunctive bare metal stent was used in 8 (9%) limbs deployed in the EIA. RESULTS: There were 31 limb occlusions, all unilateral: 17 (3%) patients in the CIA group had an occluded limb (1% of limbs at risk) vs. 14 (15%) patients in the EIA group (12% of limbs at risk; p<0.0001). The median time to occlusion was 3 months (0-60) in the CIA group and 1 month (0-36) in the EIA group. The majority of occlusions were treated by extra-anatomical revascularization, most often a femorofemoral crossover bypass. No legs were amputated following occlusion of a limb placed in the CIA, but there were 3 amputations in the EIA group (p=0.003). CONCLUSION: Deployment of endograft limbs into the EIA led to a higher rate of occlusion and leg amputation. Increased tortuosity of the EIA and a smaller caliber vessel are likely to account for the increased risk. PMID- 22313207 TI - Strategies that minimize the risk of iliac limb occlusion after EVAR. PMID- 22313208 TI - Endovascular repair is associated with superior clinical outcomes in patients transferred for treatment of ruptured abdominal aortic aneurysms. AB - PURPOSE: To compare in a population-based analysis the in-hospital mortality and complications following endovascular aneurysm repair (EVAR) vs. open repair in patients transferred for the management of ruptured abdominal aortic aneurysm (RAAA). METHODS: Interrogation of the 2003-2007 Nationwide Inpatient Sample database identified 271 patients (205 men; mean age 71.7 years) who were transferred for RAAA treatment. Demographic, patient, and hospital characteristics were analyzed. Hierarchical multivariate logistic regression analyses were employed to identify predictors of in-hospital mortality and complications; results are presented as the odds ratio (OR) and 95% confidence interval (CI). RESULTS: In comparison to open repair (n=207), endovascular repair (n=64) was associated with lower in-hospital mortality (36% vs. <18%, p<0.01) and a lower complication rate (78% vs. 66%, p<0.05). Transferred RAAA patients undergoing EVAR had lower in-hospital mortality (OR 0.21, 95% CI 0.09 to 0.49, p<0.01) and fewer complications (OR 0.49, 95% CI 0.26 to 0.95, p<0.05) than transferred patients having open repair. CONCLUSION: Compared to open repair, EVAR led to superior short-term clinical outcomes in transferred RAAA patients. In this clinical situation, transfer of stable RAAA patients to institutions capable of performing EVAR is recommended. PMID- 22313209 TI - Techniques for removing bilateral renal artery stents prior to fenestrated endovascular aneurysm repair. AB - PURPOSE: To demonstrate 2 endovascular methods for successful intravascular stent extraction. TECHNIQUE: In preparation for fenestrated endovascular aneurysm repair, renal artery stents may be implanted for focal vessel stenosis at the ostium. In a recent case, bilateral renal artery stents were deployed with >50% protruding into the aortic lumen, thus rendering fenestrated endografting impossible. Two techniques were employed to extract the stents. In the left renal artery, the stent was extracted using an endovascular snare, but the right renal artery stent could not be removed with this method. Instead, an endoscopic forceps was advanced down a 16-F sheath, and the stent was grasped, extracted, and released into the aneurysm sac. The endovascular repair then proceeded in the usual fashion. CONCLUSION: The need to remove a stent prior to endovascular aneurysm repair is not a common problem encountered by most endovascular specialists; however, these methods should be in their armamentarium should the need arise. PMID- 22313210 TI - Use of regional mechanical properties of abdominal aortic aneurysms to advance finite element modeling of rupture risk. AB - PURPOSE: To investigate the use of regional variations in the mechanical properties of abdominal aortic aneurysms (AAA) in finite element (FE) modeling of AAA rupture risk, which has heretofore assumed homogeneous mechanical tissue properties. METHODS: Electrocardiogram-gated computed tomography scans from 3 male patients with known infrarenal AAA were used to characterize the behavior of the aneurysm in 4 different segments (posterior, anterior, and left and right lateral) at maximum diameter and above the infrarenal aorta. The elasticity of the aneurysm (circumferential cyclic strain, compliance, and the Hudetz incremental modulus) was calculated for each segment and the aneurysm as a whole. The FE analysis inclusive of prestress (pre-existing tensile stress) produced a detailed stress pattern on each of the aneurysm models under pressure loading. The 4 largest areas of stress in each region were considered in conjunction with the local regional properties of the segment to define a specific regional prestress rupture index (RPRI). RESULTS: In terms of elasticity, there were average reductions of 68% in circumferential cyclic strain and 63% in compliance, with a >5-fold increase in incremental modulus, between the healthy and the aneurysmal aorta for each patient. There were also regional variations in all elastic properties in each individual patient. The average difference in total stress inclusive of prestress was 59%, 67%, and 15%, respectively, for the 3 patients. Comparing the strain from FE models with the CT scans revealed an average difference in strain of 1.55% for the segmented models and 3.61% for the homogeneous models, which suggests that the segmented models more accurately reflect in vivo behavior. RPRI values were calculated for each segment for all patients. CONCLUSION: A greater understanding of the local material properties and their use in FE models is essential for greater accuracy in rupture prediction. Quantifying the regional behavior will yield insight into the changes in patient-specific aneurysms and increase understanding about the progression of aneurysmal disease. PMID- 22313211 TI - Endovascular treatment of a tuberculous thoracoabdominal aneurysm with the Multilayer stent. AB - PURPOSE: To describe a case of multiple thoracoabdominal aneurysms of tuberculous origin treated in an endovascular procedure with the Multilayer stent. CASE REPORT: A 16-year-old girl had been treated 4 years previously for a ruptured abdominal aortic aneurysm of tuberculous origin. Due to the presence of 4 rapidly evolving saccular aneurysms of the descending thoracic aorta and a fusiform aneurysm of the suprarenal aorta, an endovascular solution was chosen after the patient refused open surgery. Three uncovered Multilayer stents (16*40, 16*80, and 16*80 mm) were successively implanted with a 1-cm overlap from the left subclavian artery to cover the entire aneurysmal segment of the thoracoabdominal aorta to above the renal arteries. At 18 months, serial imaging studies have shown disappearance of some aneurysms and regression of others. CONCLUSION: In this young patient, the endovascular treatment of a thoracoabdominal aneurysm with an uncovered stent made it possible to stabilize the aneurysm process without exposing the patient to the high morbidity and mortality of open surgery. PMID- 22313212 TI - Treatment of juxtarenal aortic aneurysm with the Multilayer stent. AB - PURPOSE: To report the use of a new type of uncovered stent to treat aortic aneurysms. CASE REPORT: Under compassionate use, an 81-year-old man with multiple comorbidities and an expanding 63-mm juxtarenal abdominal aortic aneurysm was treated with a 28*100-mm Multilayer flow-modulating stent. Immediately, the blood flow velocity inside the aneurysm sac appeared reduced on fluoroscopy. All aortic branches covered by the stent (celiac trunk, superior mesenteric artery, and renal arteries) remained patent. Serial computed tomography at up to 12 months has shown excellent stent and visceral artery patency and progressive reduction in the sac diameter (58 mm) and volume (84.9 cm(3) to 82.8 cm(3)). CONCLUSION: This case shows that the use of an uncovered multilayer stent reduces the flow in the aneurysm but preserves perfusion of the branch arteries, which is impossible with covered stents. PMID- 22313213 TI - Treatment of complex thoracoabdominal or juxtarenal aortic aneurysms with a Multilayer stent. PMID- 22313214 TI - Type II endoleak: from treatment of a complication to prevention. PMID- 22313215 TI - RE: "Branched grafts for thoracoabdominal aneurysms: off-label use of FDA approved devices". PMID- 22313216 TI - How successful are small-diameter implants? A literature review. AB - BACKGROUND: Edentulism is an important issue and will remain so due to high numbers of edentate individuals worldwide. For many years, complete dentures have been the only treatment option for this population. Implant overdentures have been shown to have many advantages over conventional complete dentures. However, although dissatisfied with their mandibular dentures, some edentate elders are reluctant to undergo even simple implant treatment due to factors such as cost and fear of surgery. To address these obstacles, this paper reports on a review of small-diameter implant (SDI) studies that were performed in the last two decades. The aim of this study is to (i) determine the survival of narrow diameter implants, (ii) determine whether survival is dependent on whether these implants are placed using a flap or flapless approach, and (ii) determine whether there is a relationship between length and implant survival in SDIs. METHODS: In this review, studies were included that (i) involve implants with 3.5 mm diameter or less, (ii) have a randomized clinical trial, retrospective or prospective cohort design with human subjects, (iii) provide a follow up duration of at least 5 months following implant placement, (iv) include data on the survival rate of the implants. RESULTS: Forty one studies meeting the above criteria were published between 1993 and 2011 using SDIs from a variety of companies and surface characteristics with diameters of 1.8 mm to 3.5 mm and lengths of 8 mm to 18 mm. A total of 10,093 SDIs were inserted in approximately 2762 patients. Twenty-six studies involved flap reflection techniques for implant placement, six studies used a flapless technique and two studies used both techniques; in the remaining studies, the technique was not specified. Follow up duration varied from 5 months to over 9 years. The survival rate reported in all screened studies was over 90%, including eight studies in which a 100% survival rate was reported. In 22 studies, the reported survival rate ranged from 95% to 99.9%. Failure was reported most often in short SDIs (less than or equal 13 mm) (n = 88) compared to longer ones (more than 13 mm). CONCLUSION: Survival rates reported for SDI are similar to those reported for standard width implants. These survival rates did not appear to differ between studies that used flapless and flap reflection techniques. The failure rate appeared to be higher in shorter SDIs than in longer ones in the studies in which the length of the failed implants was reported. SDIs could be considered for use with fixed restorations and mandibular overdentures, since their success rate appears to be comparable to that of regular diameter implants. They might also be an efficient, low-cost solution for elders who wish to reduce problems with denture instability. PMID- 22313217 TI - Depression and severe heart failure: benefits of cardiac resynchronization therapy. AB - BACKGROUND: The relationship between depression and heart failure is neither coincidental nor trivial, since depression is a powerful predictor of re hospitalization and mortality. We prospectively studied the prevalence and impact of depression on the clinical outcomes of patients attending for cardiac resynchronization therapy (CRT). We specifically examined whether patients with depression have a different rate of response to CRT and whether CRT has an effect on depressive symptoms. METHODS: Sixty-eight recipients of CRT systems were included. The depressive status was evaluated before implant and after 6 months by a structured diagnostic interview measuring Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria of major depression and by a self-report questionnaire (Center for Epidemiological Studies Depression Scale, CES-D). The CRT response was assessed at 6 months by a clinical composite score. RESULTS: At inclusion, DSM-IV criteria of major depression were identified in 41% of the population, while using the self-report questionnaire 65% were observed to have mild to major depressive symptoms (CES-D >= 16). Only 4 patients were taking antidepressants. At 6 months, 75% were considered responders to CRT. Response to CRT did not differ between those with and without depression at baseline. The rate of patients with depression at 6 months was significantly lower in responders to CRT compared with nonresponders. CONCLUSIONS: We found a high prevalence of depressive symptoms in patients receiving CRT systems. Patients with depression should not be excluded from CRT, because they demonstrate a similar rate of response than the persons without depression and the responders are less likely to be depressed at 6 months. PMID- 22313218 TI - Embryo morphology as a predictor of IVF success: an evaluation of the proposed UK ACE grading scheme for cleavage stage embryos. AB - This study aims to provide a first evaluation of the morphological embryo grading scheme proposed in the British Fertility Society and Association of Clinical Embryologist joint guidelines for elective single embryo transfer. Pregnancy data were obtained from a cohort of patients treated at St. Mary's Hospital in Manchester, UK, between April 2007 and July 2009. Embryo morphology was assessed on day 2 or 3 prior to transfer in terms of 3 parameters: cell number, fragmentation and evenness. Cell number was parameterised as a growth rate (doublings/day). An embryo-uterus model with adjustment for other prognostic factors was used to determine the role of the three components as predictors of pregnancy. Embryo growth rate (p < 0.001) and fragmentation (p = 0.004) were strong predictors of pregnancy and after including these, evenness did not improve the prediction significantly (p = 0.39). Normally growing embryos have a higher implantation rate than slow and fast-growing embryos. The grading scheme has proved to be feasible and robust in routine clinical practice. Based on this single-centre retrospective series we propose a selection algorithm for day 2/3 embryos based on fragmentation and growth rate. The 3 parameter grading scheme has the potential for further discrimination as larger datasets become available. PMID- 22313219 TI - The link between infertility and poverty: evidence from Bangladesh. AB - The link between high fertility and poverty is well established. However, this paper shows how infertility may also generate poverty among childless families in Bangladesh. An ethnographic study was conducted, involving various qualitative research methods that revealed economic consequences to be one of the crucial sequelae of childlessness in Bangladesh. This paper details how the poverty/fertility relationship is dependent on social and institutional characteristics, including patriarchal values, education, urban-rural location and health services. Empirical data show that childlessness generates poverty in various ways, including the deprivation of children's earnings, decline in women's mobility, demoralisation of men to earn an income, marriage devaluation by the husband, disbursements for treatment and denial of microcredit (very small loans to those in poverty, which support them to become self-employed to generate income). The current study shows that the infertility/poverty relationship is mostly contingent upon class and gender. It is therefore the rural poor childless women who are most badly affected economically in Bangladesh rather than the urban middle class childless women. In other words, this study reveal that along with gender, class plays a dominant role in terms of the economic consequences of childlessness in Bangladesh. It sheds light on a different and unusual aspect of poverty and aims to contribute to the gender discussion of livelihood and poverty. PMID- 22313226 TI - A NAC transcription factor NTL4 promotes reactive oxygen species production during drought-induced leaf senescence in Arabidopsis. AB - Reactive oxygen species (ROS) are produced in plant cells primarily as by products of aerobic energy metabolism. They are also generated during plant adaptation responses to environmental stresses, such as drought and high salinity. Therefore, plants have evolved ROS-detoxifying enzymes and antioxidants to cope with ROS accumulation. However, if stress conditions are prolonged, the level of ROS will surpass the capacity of the detoxifying machinery, causing oxidative damage to cellular constituents. It is known that ROS act in abscisic acid-mediated stress responses to sustain plant survival under adverse growth conditions. However, it is largely unknown how ROS metabolism is linked to stress responses. Here, we show that a drought-responsive NAC transcription factor NTL4 promotes ROS production by binding directly to the promoters of genes encoding ROS biosynthetic enzymes during drought-induced leaf senescence. Leaf senescence was accelerated in 35S:4DeltaC transgenic plants over-expressing an active form of NTL4 under drought conditions. The 35S:4DeltaC transgenic plants were hypersensitive to drought, and ROS accumulated in the leaves. In contrast, ROS levels were reduced in NTL4-deficient ntl4 mutants, which exhibited delayed leaf senescence and enhanced drought resistance. These observations indicate that NTL4 acts as a molecular switch that couples ROS metabolism to drought-induced leaf senescence in Arabidopsis. PMID- 22313228 TI - Ictal epileptic headache as "subtle" symptom in generalized idiopathic epilepsy. AB - Epilepsy and migraine are common neurologic chronic disorders with episodic manifestations characterized by recurrent attacks and a return to baseline conditions between attacks. Epilepsy and migraine are frequently observed in comorbidity, with the occurrence of one disorder increasing the probability of the other: Migraine occurs in about one-fourth of patients with epilepsy, whereas epilepsy is present in 8-15% of patients with migraine. The link between headache and seizures is controversial and multifactorial. In epilepsy, headache can be seen as a preictal, ictal, or postictal phenomenon. In this report, we describe a case of a 37-year-old patient, affected by both drug-resistant generalized idiopathic epilepsy and headache, who displayed the sudden onset of a headache attack referred during a 24-h electroencephalography (EEG). The EEG tracing during this event revealed the activation of subcontinuous epileptic activity consisting of generalized spike-wave discharges (GSWDs) and generalized polyspike and wave discharges (GPSWDs) that persisted for 60 min, that is, until the disappearance of the headache. The case we describe appears to be original in that it represents one of the few EEG-documented ictal epileptic headaches in generalized idiopathic epilepsy. PMID- 22313227 TI - Radiosynthesis and evaluation of an (18)F-labeled positron emission tomography (PET) radioligand for brain histamine subtype-3 receptors based on a nonimidazole 2-aminoethylbenzofuran chemotype. AB - A known chemotype of H(3) receptor ligand was explored for development of a radioligand for imaging brain histamine subtype 3 (H(3)) receptors in vivo with positron emission tomography (PET), namely nonimidazole 2-aminoethylbenzofurans, represented by the compound (R)-(2-(2-(2-methylpyrrolidin-1-yl)ethyl)benzofuran-5 yl)(4-fluorophenyl)methanone (9). Compound 9 was labeled with fluorine-18 (t(1/2) = 109.7 min) in high specific activity by treating the prepared nitro analogue (12) with cyclotron-produced [(18)F]fluoride ion. [(18)F]9 was studied with PET in mouse and in monkey after intravenous injection. [(18)F]9 showed favorable properties as a candidate PET radioligand, including moderately high brain uptake with a high proportion of H(3) receptor-specific signal in the absence of radiodefluorination. The nitro compound 12 was found to have even higher H(3) receptor affinity, indicating the potential of this chemotype for the development of further promising PET radioligands. PMID- 22313229 TI - An effective strategy for the synthesis of biocompatible gold nanoparticles using danshensu antioxidant: prevention of cytotoxicity via attenuation of free radical formation. AB - To suppress the cytotoxicity of gold nanoparticles (AuNPs), danshensu, a naturally occurring polyphenol antioxidant isolated from Chinese herb, was used to provide a fundamental protection layer for AuNPs, to alleviate oxidative stress and as a reducing agent to react with chloroauric acid. Besides danshensu, gum arabic was chosen as an auxiliary stabilising agent to improve the stability of AuNPs against aggregation. As expected, the prepared GA-DS-AuNPs (gum arabic danshensu-gold nanoparticle) was remarkably stable in various buffer solutions. More interestingly, the GA-DS-AuNPs not only did not show any appreciable cytotoxicity, but also could alleviate the oxidative damage induced by AuNPs. Meanwhile, the ROS/RNS scavenging activities of GA-DS-AuNPs was evaluated by electron spin resonance spectroscopy (ESR), potentiometric nitric oxide (NO) sensor and cell confocal imaging. The results suggest that GA-DS-AuNPs might have effectively reduced the AuNPs-induced cytotoxicity and oxidative stress by downregulation of ROS/NOS production. The GA-DS-AuNPs may provide potential opportunities for the application in nanomedicine and nanobiology. PMID- 22313230 TI - Reversible visible-light tuning of self-organized helical superstructures enabled by unprecedented light-driven axially chiral molecular switches. AB - Two enantiomeric light-driven azo molecular switches with axial chirality and extended conjugation were found to exhibit unprecedented reversible photoisomerization in both organic-solvent and liquid-crystal media only upon visible-light irradiation. When doped in an achiral liquid crystal with a different concentration, the chiral switch was able either to immediately induce an optically tunable helical superstructure or to retain an achiral liquid crystal phase whose helical superstructure was induced and tuned reversibly upon visible-light irradiation. Furthermore, reversible dynamic red, green, and blue reflection achieved only by using visible light was demonstrated. PMID- 22313231 TI - Controlled modulation of diameter and composition along individual III-V nitride nanowires. AB - Semiconducting nanowires have unique properties that are distinct from their bulk counterparts, but realization of their full potential will be ultimately dictated by the ability to control nanowire structure, composition, and size with high accuracy. Here, we report a simple, yet versatile, approach to modulate in situ the diameter, length, and composition of individual segments within (In,Ga)N nanowires by tuning the seed particle supersaturation and size via the supply of III and V sources during the growth. By elucidating the underlying mechanisms controlling structural evolution, we demonstrate the synthesis of axial InN/InGaN nanowire heterojunctions in the nonpolar m-direction. Our approach can be applied to other materials systems and provides a foundation for future development of complex nanowire structures with enhanced functionality. PMID- 22313232 TI - Uptake measurements of acetic acid on ice and nitric acid-doped thin ice films over upper troposphere/lower stratosphere temperatures. AB - The adsorption of gaseous acetic acid (CH(3)C(O)OH) on thin ice films and on ice doped with nitric acid (1.96 and 7.69 wt %) was investigated over upper troposphere and lower stratosphere (UT/LS) temperatures (198-208 K), and at low gas concentrations. Experiments were performed in a Knudsen flow reactor coupled to a quadrupole mass spectrometer. The initial uptake coefficients, gamma(0), on thin ice films or HNO(3)-doped ice films were measured at low surface coverage. In all cases, gamma(0) showed an inverse temperature dependence, and for pure thin ice films, it was given by the expression gamma(0)(T) = (4.73 +/- 1.13) * 10(-17) exp[(6496 +/- 1798)/T]; the quoted errors are the 2sigma precision of the linear fit, and the estimated systematic uncertainties are included in the pre exponential factor. The inverse temperature dependence suggests that the adsorption process occurs via the formation of an intermediate precursor state. Uptakes were well represented by the Langmuir adsorption model, and the saturation surface coverage, N(max), on pure thin ice films was (2.11 +/- 0.16) * 10(14) molecules cm(-2), independent of temperature in the range 198-206 K. Light nitration (1.96 and 7.69 wt %) of ice films resulted in more efficient CH(3)C(O)OH uptakes and larger N(max) values that may be attributed to in-bulk diffusion or change in nature of the gas-ice surface interaction. Finally, it was estimated that the rate of adsorption of acetic acid on high-density cirrus clouds in the UT/LS is fast, and this is reflected in the short atmospheric lifetimes (2-8 min) of acetic acid; however, the extent of this uptake is minor resulting in at most a 5% removal of acetic acid in UT/LS cirrus clouds. PMID- 22313233 TI - AHRQ's comparative effectiveness research on oral medications for type 2 diabetes: a summary of the key findings. AB - BACKGROUND: In 2007, the Agency for Healthcare Research and Quality(AHRQ) published a systematic review on the comparative effectiveness of oral medications for type 2 diabetes. The review included studies on the benefits and risks of oral medications used for achieving glycemic control in patients with type 2 diabetes. AHRQ published an updated review in March 2011 that summarized the benefits and harms of medications (metformin,second-generation sulfonylureas, thiazolidinediones, meglitinides,dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists), as monotherapy and in combination, for the treatment of adults with type 2 diabetes. OBJECTIVES: To (a) familiarize health care professionals with the methods and findings from AHRQ's 2011 comparative effectiveness review on medications for adults with type 2 diabetes, (b) encourage consideration of the clinical and managed care applications of the review findings, and(c) identify limitations and gaps in the existing research with respect to the benefits and risks of oral diabetes medications. SUMMARY: Type 2 diabetes mellitus is a major public health burden. Since the 2007 AHRQ systematic review of oral medications for type 2 diabetes, the FDA has approved several new drug classes. Therefore, in 2011, the original systematic review was updated with comparisons including the newer oral diabetes medications. The updated report expands beyond the scope of the original 2007 review by including comparisons of 2-drug combinations and the addition of more head-to-head comparisons, as well as additional adverse outcomes. A high strength of evidence showed that most medications were similarly efficacious at lowering hemoglobin A1c by about 1 absolute percentage point compared with baseline values. The addition of most oral medications to initial monotherapy further improved glycemiccontrol by lowering A1c by another 1 percentage point. The only exception was the DPP-4 inhibitor class, which did not lower A1c to the same extent as metformin when used as monotherapy. Overall, metformin was found to have a more favorable effect on body weight when compared with other medications. Two-drug combinations compared with each other demonstrated similar reductions in A1c levels. Metformin decreased low-density lipoprotein cholesterol (LDL-C) relative to pioglitazone, sulfonylureas,and DPP-4 inhibitors. Sulfonylureas had a 4-fold higher risk of mild-to-moderate hypoglycemia compared with metformin alone, and, in combination with metformin, had more than a 5-fold increased risk compared with metformin plus a thiazolidinedione. Thiazolidinediones had an increased risk of congestive heart failure relative to sulfonylureas, and an increased risk for bone fractures relative to metformin. Diarrhea occurred more often for metformin users compared with thiazolidinedione users. Although the long-term risks and benefits of diabetes medications remain unclear, the evidence supports the use of metformin as a first-line agent. PMID- 22313234 TI - Pathogenesis and treatment of leukemia: an Asian perspective. AB - INTRODUCTION: Leukemias occur worldwide, but there are important geographic differences in incidences. AREAS COVERED: Three leukemias with special Asian perspectives, acute promyelocytic leukemia (APL), T-cell large granular lymphocyte (T-LGL) leukemia and NK-cell leukemia. EXPERT OPINION: In APL, China has made contributions in discovering the efficacy of all-trans retinoic acid (ATRA) and arsenic trioxide. Some APL patients are potentially curable after treatment with ATRA or arsenic trioxide as a single agent. Combined treatment of APL with ATRA and arsenic trioxide induces remission with deeper molecular response. An oral formulation of arsenic trioxide is available, making outpatient treatment feasible. Future regimens for APL should examine how ATRA and arsenic trioxide can be optimally combined with other synergistic drugs. Asian patients with T-LGL leukemia present more frequently with pure red cell aplasia, but less frequently with neutropenia, recurrent infection, splenomegaly and rheumatoid arthritis as compared with Western patients. These differences have potential effects on treatment and disease pathogenesis. NK-cell leukemia is rapidly fatal and occurs almost exclusively in Asian and South American patients. Conventional anthracycline-based chemotherapy designed for B-cell lymphomas do not work in NK cell leukemias. Novel therapeutic approaches targeting cellular signaling pathways or preferentially upregulated genes are needed to improve outcome. PMID- 22313235 TI - Biological pump control of the fate and distribution of hydrophobic organic pollutants in water and plankton. AB - The goal of this study was to experimentally assess the coupling between primary producer biomass dynamics and the distribution and fate of persistent organic pollutants (POPs) in a lake pelagic ecosystem. This was done by following the short-term evolution of polychlorinated biphenyl (PCB) concentrations in water and biota (phytoplankton and zooplankton) and the variability of bioconcentration (BCF), biomagnification (BMF), and bioaccumulation (BAF) factors during the development of a typical spring ecological progression in which the phytoplankton bloom is followed by a peak in the zooplankton abundance. The bulk of compounds with log K(OW) > 6.5 in the lake epilimnion was mainly associated with primary producer biomass. The phytoplankton biological pump was a major driver of POP export from the epilimnion, causing the decline of dissolved-phase concentrations. The BCF of phytoplankton for the more hydrophobic PCBs showed minima during the period of biomass climax. The concentration in the zooplankton of all selected PCBs sharply declined from March to May, with BAFs having minima in the post algal bloom phase. Biomagnification occurred during the pre algal bloom and algal bloom phases but appeared to be absent during the post algal bloom. This study highlights the occurrence of a prompt and complex response in the fate and distribution of POPs to dynamic biogeochemical control. Within the frame of the ecological succession, phytoplankton and zooplankton biomass dynamics produced bioaccumulation metrics varying over 1-2 orders of magnitude in the time frame of a few weeks and resulted in reduced trophic web exposure. PMID- 22313236 TI - Brown midrib2 (Bmr2) encodes the major 4-coumarate:coenzyme A ligase involved in lignin biosynthesis in sorghum (Sorghum bicolor (L.) Moench). AB - Successful modification of plant cell-wall composition without compromising plant integrity is dependent on being able to modify the expression of specific genes, but this can be very challenging when the target genes are members of multigene families. 4-coumarate:CoA ligase (4CL) catalyzes the formation of 4-coumaroyl CoA, a precursor of both flavonoids and monolignols, and is an attractive target for transgenic down-regulation aimed at improving agro-industrial properties. Inconsistent phenotypes of transgenic plants have been attributed to variable levels of down-regulation of multiple 4CL genes. Phylogenetic analysis of the sorghum genome revealed 24 4CL(-like) proteins, five of which cluster with bona fide 4CLs from other species. Using a map-based cloning approach and analysis of two independent mutant alleles, the sorghum brown midrib2 (bmr2) locus was shown to encode 4CL. In vitro enzyme assays indicated that its preferred substrate is 4 coumarate. Missense mutations in the two bmr2 alleles result in loss of 4CL activity, probably as a result of improper folding as indicated by molecular modeling. Bmr2 is the most highly expressed 4CL in sorghum stems, leaves and roots, both at the seedling stage and in pre-flowering plants, but the products of several paralogs also display 4CL activity and compensate for some of the lost activity. The contribution of the paralogs varies between developmental stages and tissues. Gene expression assays indicated that Bmr2 is under auto-regulatory control, as reduced 4CL activity results in over-expression of the defective gene. Several 4CL paralogs are also up-regulated in response to the mutation. PMID- 22313237 TI - Voltage-induced adsorbate damping of single gold nanorod plasmons in aqueous solution. AB - Unbiased gold nanoparticles are negatively charged in aqueous solution but not hydrated. Optical spectroscopy of voltage-clamped single gold nanoparticles reveals evidence that anion adsorption starts at positive potentials above the point of zero charge, causing severe but reversible plasmon damping in combination with a spectral red shift exceeding the linear double layer charging effect. Plasmon damping by adsorbate is relevant for the use of nanoparticles in catalysis, in biodiagnostics, and in surface enhanced Raman scattering. PMID- 22313238 TI - Increase in antioxidant gene transcripts, stress tolerance and biocontrol efficacy of Candida oleophila following sublethal oxidative stress exposure. AB - A pretreatment of the yeast, Candida oleophila, with 5 mM H(2)O(2) for 30 min (sublethal) increased yeast tolerance to subsequent lethal levels of oxidative stress (50 mM H(2)O(2)), high temperature (40 degrees C), and low pH (pH 4). Compared with non-stress-adapted yeast cells, stress-adapted cells exhibited better control of apple fruit infections by Penicillium expansum and Botrytis cinerea and had initially higher growth rates in apple wounds. Suppression subtractive hybridization analysis was used to identify genes expressed in yeast in response to sublethal oxidative stress. Transcript levels were confirmed using semiquantitative reverse transcription-PCR. Seven antioxidant genes were upregulated. The elevated expression of these genes was associated with less accumulation of reactive oxygen species and a lower level of protein and lipid oxidation under subsequent stresses. These data support the premise that induction of abiotic stress tolerance in biocontrol yeast can improve biocontrol efficacy by upregulation of genes involved in the amelioration of oxidative stress. PMID- 22313239 TI - Neurodevelopmental delay among HIV-infected preschool children receiving antiretroviral therapy and healthy preschool children in Soweto, South Africa. AB - Neurodevelopmental delay has been documented in up to 97.5% of HIV-infected children in Soweto who were not yet on antiretroviral treatment (ART). With growing numbers of children in South Africa being successfully treated with ART, the effects of ART on neurocognitive functioning in children require investigation. The objective of this study was to determine the extent of neurodevelopmental delay in stable HIV-infected preschool children (aged five to six years) receiving ART and compare it to an apparently healthy (unconfirmed HIV status) group of preschool children. Thirty HIV-infected preschool children (virologically and immunologically stable on ART for more than one year) were conveniently sampled from 350 eligible children on ART at the Harriet Shezi Children's Clinic in Soweto, Johannesburg. The comparison group comprised 30 well nourished preschool children attending the Lilian Ngoyi Primary Health Care Clinic in Soweto for routine immunizations. Each child was assessed using the Griffiths Mental Development Scales-Extended Revised Version (GMDS-ER), at a single point in time. The overall developmental z-scores on GMDS-ER were <-2 (indicating severe delay) in 27 (90%) children in the HIV-infected group compared to 23 (76%) in the comparison group (p = 0.166). Mental handicap (overall GQ < 70) was evident in 46.7% of children in the HIV-infected group compared to 10% in the comparison group (p = 0.002). There was a 7.88-fold increased likelihood of severe delay in the HIV infected group. The HIV-infected group and comparison group had significantly different (p = 0.001) mean overall GQ scores of 70 (95% CI: 66.0-74.0) and 78 (95% CI: 75.6-80.5), respectively, with lower mean scores in the HIV-infected group in all individual domains. Early initiation of ART in HIV-infected infants may improve cognitive functioning among this group; however, intervention strategies which optimize early cognitive development for all children in the area need to be urgently considered. PMID- 22313240 TI - Incidence of asymptomatic cerebral microthromboembolism after atrial fibrillation ablation guided by complex fractionated atrial electrogram. AB - BACKGROUND: The incidence of cerebral thromboembolism after pulmonary vein isolation (PVI) ranges from 2% to 14%. This study investigated the incidence of cerebral thromboembolism after complex fractionated atrial electrogram (CFAE) ablation with or without PVI. METHODS: One hundred consecutive atrial fibrillation (AF) patients (50 paroxysmal and 50 persistent, including 10 longstanding) who underwent CFAE ablation combined with (n = 41, PVI+CFAE group) or without (n = 59, CFAE group) PVI were studied. Coronary angiography (CAG) was conducted with AF ablation in 5 cases in which coronary artery stenosis was suspected on 3D-computed tomography. PVI was performed before CFAE ablation without circular catheter during AF. After termination of AF, additional ablation was performed to complete PVI with a circular catheter. All patients underwent cerebral magnetic resonance imaging (MRI) including diffusion-weighted MRI and T2 weighted MRI the day after ablation. RESULTS: New thromboembolism was detected in 7.0%, and there was no significant difference between the 2 strategies (7.3% in PVI+CFAE group, 6.8% in CFAE group). CHADS2 score (1.6 +/- 1.0 vs 0.8 +/- 0.9, P < 0.05), left atrial volume (LAV; 83.8 +/- 27.1 vs 67.8 +/- 21.8, P < 0.05), and left ventricular ejection fraction (LVEF, 53.1 +/- 9.2 vs 65.1 +/- 9.7, P < 0.01) were significantly different when comparing patients with or without thromboembolism. In multivariate analysis, LVEF (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.84-0.99; P < 0.05) and concomitant CAG (OR 18.82; 95% CI, 1.77-200.00; P < 0.05) were important predictors of new cerebral thromboembolism. CONCLUSIONS: The incidence of cerebral microthromboembolism after CFAE ablation was not greater than previous reports in PVI. Cautious management is required during AF ablation, especially in the patients with low LVEF. PMID- 22313241 TI - Pediatric and adult eosinophilic esophagitis: similarities and differences. AB - Early in the 1990s, several case series described adults suffering from dysphagia and children with refractory reflux symptoms, both accompanied by an eosinophil predominant infiltration, thereby conclusively distinguishing it from gastroesophageal reflux disease. Eosinophilic esophagitis (EoE) was recognized as its own entity in the adult and in the pediatric literature. In the last decade, evidence has accumulated that EoE represents a T-helper (Th)2-type inflammatory disease. Remodeling of the esophagus is a hallmark of EoE, leading to esophageal dysfunction and bolus impaction. Familial occurrence and disease association with single-nucleotide polymorphisms underscore the influence of genetics in this disease. Eosinophilic esophagitis may affect individuals at any age, although the clinical presentation is highly age dependent. There is a significant allergic bias in the EoE population, with the majority of patients having concurrent allergic rhinitis, asthma, eczema, and/or a history of atopy. One noteworthy difference is that in children, EoE seems to be primarily a food antigen-driven disease, whereas in adults, mainly aeroallergen sensitization has been observed. Treatment modalities for EoE include the 3Ds: drugs, diet, and dilation. The crucial question of whether adult and pediatric EoE are different phenotypes of one single entity or whether we are confronted with two different diseases is still open. Here, we review similarities and differences between EoE in adults and children. PMID- 22313242 TI - 2-(Pyrrolidin-1-yl)ethyl-3,4-dihydroisoquinolin-1(2H)-one derivatives as potent and selective histamine-3 receptor antagonists. AB - On the basis of the previously reported benzimidazole 1,3'-bipyrrolidine benzamides (1), a new class of 2-(pyrrolidin-1-yl)ethyl-3,4-dihydroisoquinolin 1(2H)-one derivatives (3-50) were synthesized and evaluated as potent H(3) receptor antagonists. In particular, compound 39 exhibited potent in vitro binding and functional activities at the H(3) receptor, good selectivities against other neurotransmitter receptors and ion channels, acceptable pharmacokinetic properties, and a favorable in vivo profile. PMID- 22313243 TI - Developmental competence in oocytes and cumulus cells: candidate genes and networks. AB - Common aspects of infertility can be seen across several species. In humans, dairy cows, and mares there is only a 25-35% chance of producing a live offspring after a single insemination, whether natural or artificial. Oocyte quality and subsequent embryo development can be affected by factors such as nutrition, hormonal regulation, and environmental influence. The objective of this study was to identify genes expressed in oocytes and/or cumulus cells, across a diverse range of species, which may be linked to the ability an oocyte has to develop following fertilization. Performing a meta-analysis on previously published microarray data on various models of oocyte and embryo quality allowed for the identification of 56 candidate genes associated with oocyte quality across several species, 4 of which were identified in the cumulus cells that surround the oocyte. Twenty-one potential biomarkers were associated with increased competence and 35 potential biomarkers were associated with decreased competence. The upregulation of Metap2, and the decrease of multiple genes linked to mRNA and protein synthesis in models of competence, highlights the importance of de novo protein synthesis and its regulation for successful oocyte maturation and subsequent development. The negative regulation of Wnt signaling has emerged in human, monkey, bovine, and mouse models of oocyte competence. Atrx expression was linked to decreased competence in both oocytes and cumulus cells. Biological networks and transcription factor regulation associated with increased and decreased competence were also identified. These genes could potentially act as biomarkers of oocyte quality or as pharmacological targets for manipulation in order to improve oocyte developmental potential. PMID- 22313244 TI - Burkitt lymphoma in Uganda, the legacy of Denis Burkitt and an update on the disease status. AB - Burkitt lymphoma (BL) was first described in Uganda in 1958 as a sarcoma of the jaw but later confirmed to be a distinct form of Non Hodgkin lymphoma (NHL). This discovery was the defining moment of cancer research in Uganda, which eventually led to the establishment of a dedicated cancer research institute, the Uganda Cancer Institute (UCI) in 1967. The centre was dedicated to Denis Burkitt in recognition of his contribution to cancer research in East Africa. BL is still the commonest NHL in childhood in Uganda. Its incidence has significantly increased recently due to yet unknown factors. Although the human immunodeficiency virus (HIV) was considered a possible reason for the increase, there is no evidence that it has substantially impacted on the epidemiology of the disease. However, for those patients with BL who are co infected with HIV there is a clear impact of the disease on clinical presentation and outcome. HIV infected patients commonly present with extra facial sites and tend to have poor overall survival (median survival of 11.79 months). In summary, BL, as a disease entity in Uganda, has maintained the same clinical characteristics since its discovery, despite the emergence of HIV during the intervening period. PMID- 22313245 TI - The effects of endosulfan on the growth and erythrocyte immune function of Mongolian gerbils (Meriones unguiculatus). AB - To investigate the effects of endosulfan on erythrocyte immune functions in Mongolian gerbils, 50 Mongolian gerbils were randomly divided into five groups. They were administered endosulfan by gavage at dosages of 0, 0.4, 0.8, 1.6, and 6.4 mg/(kg/d). After 21 days, the daily weight gain and organ weight index were determined, and blood was collected to examine the erythrocyte immune functions. The results indicated that the effect of endosulfan dosage on daily weight gain was not significant. The liver index in the 6.4 mg/(kg/d) endosulfan group was significantly higher than that of the control group. The rosetting ratios of the erythrocyte C(3)b receptor (E-C(3)bR) significantly decreased with increasing endosulfan dosage to 9.94%, 8.59%, 8.13%, 7.84%, and 7.40%, respectively, with respect to the control group. The rosetting ratios of erythrocyte immune complexes (E-ICs) also decreased to 5.13%, 5.09%, 4.38%, 4.34% and 3.83%, respectively, with respect to the control group. There was no significant difference in the natural killer cell (NK) activity regulated by erythrocytes among the five groups. The erythrocyte innate immune inhibitory factor activity in the 1.6 mg/(kg/d) endosulfan group significantly increased, as compared with the activity in the control group. These results suggested that endosulfan can inhibit the erythrocyte immune adherent function, promote the activity of inhibitory factor, and increase the liver weight index; however, there were no significant effects on daily weight gain or the activity of the enhancing factor in Mongolian gerbils. PMID- 22313246 TI - Pd(II)/Bronsted acid catalyzed enantioselective allylic C-H activation for the synthesis of spirocyclic rings. AB - A Pd(II)/Bronsted acid catalyzed migratory ring expansion for the synthesis of indene derivatives possessing a stereogenic spirocyclic carbon center was developed. This transformation is believed to mechanistically proceed via enantioselective allylic C-H activation with concomitant semipinacol ring expansion to the nascent pi-allylpalladium species. Enantioselectivities as high as 98% ee were attainable. PMID- 22313247 TI - The effect of collagenated space filling materials in sinus bone augmentation: a study in rabbits. AB - AIM: The inclusion of biomaterial particles used for alveolar bone regeneration in a carrier or in binding agents such as collagen gel or fibers is of interest as a means to help with surgical handling. However, the possible influence of collagen on bone tissue response to biomaterials is poorly studied. The objective of the present study was to investigate, in a sub-sinus bone augmentation model in rabbits, the effect of collagen at different stages of the osteogenesis process. Histologic, histomorphometric and volumetric analyses were performed. MATERIALS AND METHODS: Rabbits underwent a double sinus lift procedure using bovine hydroxyapatite (BHA), collagenated bovine hydroxyapatite (BHAColl), and prehydrated and collagenated porcine hydroxyapatite (PHAColl). Animals were sacrificed at 1 week, 5 weeks or 6 months. Samples were subjected to X-ray micro tomography and histology. Qualitative analysis was performed on the non decalcified sections and quantitative histomorphometric analyses were conducted using scanning electron microscopy (SEM). Volume variations of bone augmentations were calculated at different time points. RESULTS: The three biomaterials allowed an optimal bone formation and were able to equally withstand sinusal reexpansion. A comparable percentage of new bone, as well as 3D volume stability, was found between the groups at each time point. However, the PHAColl resorption rate was significantly higher than the rates in other groups (P = 0.0003), with only 3.6% of the particles remaining at 6 months. At 1 week, both collagenated groups displayed the presence of inflammatory cells although BHA did not show any sign of inflammation. At 5 weeks and 6 months, the inflammatory process had disappeared completely in the BHAColl groups, whereas some inflammatory-like cells could still be observed around the remaining particles of PHAColl. CONCLUSIONS AND CLINICAL IMPLICATIONS: Within the limitations of this study in rabbits, the findings showed the presence of inflammatory-like cells at the early stage of bone regeneration when collagenated xenogenic biomaterials were used compared to xenogenic granules alone. Nevertheless, similar bone formation occurred and comparable 3D volumes were found at 6 months in the different groups. PMID- 22313248 TI - A Bayesian semiparametric approach for incorporating longitudinal information on exposure history for inference in case-control studies. AB - In a typical case-control study, exposure information is collected at a single time point for the cases and controls. However, case-control studies are often embedded in existing cohort studies containing a wealth of longitudinal exposure history about the participants. Recent medical studies have indicated that incorporating past exposure history, or a constructed summary measure of cumulative exposure derived from the past exposure history, when available, may lead to more precise and clinically meaningful estimates of the disease risk. In this article, we propose a flexible Bayesian semiparametric approach to model the longitudinal exposure profiles of the cases and controls and then use measures of cumulative exposure based on a weighted integral of this trajectory in the final disease risk model. The estimation is done via a joint likelihood. In the construction of the cumulative exposure summary, we introduce an influence function, a smooth function of time to characterize the association pattern of the exposure profile on the disease status with different time windows potentially having differential influence/weights. This enables us to analyze how the present disease status of a subject is influenced by his/her past exposure history conditional on the current ones. The joint likelihood formulation allows us to properly account for uncertainties associated with both stages of the estimation process in an integrated manner. Analysis is carried out in a hierarchical Bayesian framework using reversible jump Markov chain Monte Carlo algorithms. The proposed methodology is motivated by, and applied to a case control study of prostate cancer where longitudinal biomarker information is available for the cases and controls. PMID- 22313249 TI - Stable carbon isotope ratio analysis of anhydrosugars in biomass burning aerosol particles from source samples. AB - A new method for stable carbon isotope ratio analysis of anhydrosugars from biomass burning aerosol particle source filter samples was developed by employing Thermal Desorption--2 Dimensional Gas Chromatography--Isotope Ratio Mass Spectrometry (TD-2DGC-IRMS). Compound specific isotopic measurements of levoglucosan, mannosan, and galactosan performed by TD-2DGC-IRMS in a standard mixture show good agreement with isotopic measurements of the bulk anhydrosugars, carried out by Elemental Analyzer--Isotope Ratio Mass Spectrometry (EA-IRMS). The established method was applied to determine the isotope ratios of levoglucosan, mannosan, and galactosan from source samples collected during combustion of hard wood, softwood, and crop residues. delta(13)C values of levoglucosan were found to vary between -25.6 and -22.20/00, being higher in the case of softwood. Mannosan and galactosan were detected only in the softwood samples showing isotope ratios of -23.50/00 (mannosan) and -25.70/00 (galactosan). The isotopic composition of holocellulose in the plant material used for combustion experiments was determined with delta(13)C values between -28.5 and -23.70/00. The difference in delta(13)C of levoglucosan in biomass burning aerosol particles compared to the parent fuel holocellulose was found to be -1.89 (+/-0.37)0/00 for the investigated biomass fuels. Compound specific delta(13)C measurements of anhydrosugars should contribute to an improved source apportionment. PMID- 22313250 TI - The past, present and future of clinical oncology. PMID- 22313251 TI - Gate-controlled surface conduction in Na-doped Bi2Te3 topological insulator nanoplates. AB - Exploring exciting and exotic physics, scientists are pursuing practical device applications for topological insulators. The Dirac-like surface states in topological insulators are protected by the time-reversal symmetry, which naturally forbids backscattering events during the carrier transport process, and therefore offers promising applications in dissipationless spintronic devices. Although considerable efforts have been devoted to controlling their surface conduction, limited work has been focused on tuning surface states and bulk carriers in Bi(2)Te(3) nanostructures by external field. Here we report gate tunable surface conduction in Na-doped Bi(2)Te(3) topological insulator nanoplates. Significantly, by applying external gate voltages, such topological insulators can be tuned from p-type to n-type. Our results render a promise in finding novel topological insulators with enhanced surface states. PMID- 22313252 TI - Quality of life of patients with amyotrophic lateral sclerosis. AB - The aim of this study is to evaluate the correlation between different measures of quality of life (QoL), functional status and mood status in patients with amyotrophic lateral sclerosis (ALS). A sample of 40 patients with ALS was recruited and scales for the evaluation of health-related QoL (SF36), patient centered QoL (SEIQoL), functional status (ALSFRS) and depression (ZDS) have been administered to them. All the correlations (Pearson's r) between the scores have been considered and the t-test was performed in order to compare male with female patients. No correlation emerged between the different measures of QoL and functional status, apart from the scores of the Physical Functioning subscale of the SF36 which resulted positively correlated (p < 0.01) with those of the ALSFRS. Mood status resulted negatively correlated with many aspects of health related QoL but not with patient-centred QoL. Data suggest that the relationship between functional status and different domains of QoL in this population of patients with a severely compromising disease is not linear and that the satisfaction with life of the patients themselves is not strongly related to the level of physical impairment. PMID- 22313253 TI - Addition of a surfactant to tryptic soy broth allows growth of a lactic acid bacteria food antimicrobial, Escherichia coli O157:H7, and Salmonella enterica. AB - AIMS: This study aimed to determine the survival and growth of Escherichia coli O157:H7 and Salmonella enterica subsp. enterica in a medium supporting the growth of a Lactic Acid Bacteria (LAB) food antimicrobial culture. METHODS AND RESULTS: Foodborne pathogens and LAB were cultured individually in tryptic soy broth (TSB), tryptic soy broth supplemented with one g l(-1) Tween 80((r)) (TSB-T80), and de Man, Rogosa and Sharpe (MRS) broth. Growth of E. coli O157:H7 and Salmonella was similar in TSB and TSB-T80 but was significantly less in MRS. Conversely, LAB growth was similar in MRS and TSB-T80 but was significantly less in TSB. CONCLUSIONS: Supplementation of TSB with Tween 80((r)) allows growth of LAB to levels similar to that observed with MRS but does not inhibit the growth of E. coli O157:H7 and Salmonella. We present the formulation of a medium useful in studies useful for evaluating competitive inhibition of foodborne pathogens by LAB in vitro. SIGNIFICANCE AND IMPACT OF THE STUDY: This study reports the utility of TSB-T80 for the completion of in vitro competitive inhibition assays incorporating a Lactic Acid Bacteria food safety culture. PMID- 22313254 TI - Synergistic TRAIL sensitizers from Barleria alluaudii and Diospyros maritima. AB - Barleria alluaudii and Diospyros maritima were both investigated as part of an ongoing search for synergistic TRAIL (tumor necrosis factor-alpha-related apoptosis-inducing ligand) sensitizers. As a result of this study, two naphthoquinone epoxides, 2,3-epoxy-2,3-dihydrolapachol (1) and 2,3-epoxy-2,3 dihydro-8-hydroxylapachol (2), both not previously isolated from natural sources, and the known 2-methylanthraquinone (3) were identified from B. alluaudii. Time dependent density functional theory (TD-DFT) calculations of electronic circular dichroism (ECD) spectra were utilized to establish the absolute configuration of 1 and 2. Additionally, five known naphthoquinone derivatives, maritinone (4), elliptinone (5), plumbagin (6), (+)-cis-isoshinanolone (7), and ethylidene-6,6' biplumbagin (8), were isolated from D. maritima. Compounds 1, 2, and 4-6 showed varying levels of synergy with TRAIL. Maritinone (4) and elliptinone (5) showed the highest synergistic effect, with more than a 3-fold increase in activity observed with TRAIL than with compound alone. PMID- 22313255 TI - Double potentials of coronary sinus during the mitral isthmus ablation. PMID- 22313256 TI - Birth and clinical pregnancy from fresh and frozen oocytes fertilized with cryopreserved testicular spermatozoa. AB - This is the first report showing a second clinical pregnancy of a couple who already have a baby from a previous frozen embryo transfer cycle when the embryos were generated from fresh oocytes that were fertilized by intracytoplasmic sperm injection (ICSI) using frozen testicular spermatozoa (the couple have unsuccessful fresh and frozen embryo transfer cycles). Fifty-two months after the first IVF/ICSI cycle the couple had their second IVF/ICSI cycle, but the collected oocytes (n=8) were frozen because no spermatozoa was obtained from the frozen testicular tissue samples which were cryopreserved prior to the first IVF/ICSI cycle. New testicular tissue samples were obtained and frozen. Finally, 58 months after the first IVF/ICSI cycle all of the 8 frozen oocytes of the couple were thawed and fertilized by ICSI using frozen testicular spermatozoa obtained from the newly cryopreserved testicular tissue. Three embryos were transferred and the couple has an ongoing pregnancy, which is in the 20(th) week of pregnancy. Our case report shows that: 1) developmentally competent embryos can be generated by ICSI of frozen-thawed testicular spermatozoa into both fresh and frozen human oocytes, and 2) clinical pregnancy and a healthy baby can be conceived from both frozen and fresh oocytes fertilized with cryopreserved testicular spermatozoa. PMID- 22313260 TI - Drugs to treat hypertension. PMID- 22313262 TI - SOCS3 modulates interleukin-6R signaling preference in dermal fibroblasts. AB - AIMS: This study aims to investigate the mechanisms in the apparent preference for mitogen-activated protein kinase /ERK signaling through interleukin (IL)-6R in dermal fibroblasts. METHODS: Dermal fibroblasts isolated from IL-6KO mice were pretreated with specific ERK or STAT3 chemical inhibitors or SOCS3 specific siRNA and treated with rmIL-6. Phosphorylation was monitored via enzyme-linked immunosorbent assay or immunohistology. SOCS3 interaction with p120Ras-Gap was examined by co-immunoprecipitation and Western blot. Expression of MMP2 mRNA was assessed via real-time quantitative polymerase chain reaction. RESULTS: A dose response phosphorylation of ERK1/2 occurred while no STAT3 activation (p-Tyr705) was induced after IL-6 treatment, despite an increase in Ser727 phosphorylation. Inhibition of STAT3 in fibroblasts potentiated IL-6R induced ERK phosphorylation and vice versa. Phosphorylated SOCS3 and p120 RasGAP co-immunoprecipitated in response to IL-6 treatment. SOCS3 siRNA knockdown allowed STAT3 phosphorylation after rmIL-6 treatment. Chemical inhibition of IL-6R signaling altered the IL-6 modulated mRNA expression of MMP-2. CONCLUSIONS: SOCS3 interaction with p120 Ras Gap plays a role in determining the preference for IL-6R signaling through ERK in dermal fibroblasts. This study provides insight into the pleiotropic nature of IL 6 and the selective signaling mechanism elicited by the IL-6R system in dermal fibroblasts. It may further indicate a method for manipulation of IL-6R function. PMID- 22313263 TI - N(pro) of classical swine fever virus prevents type I interferon-mediated priming of conventional dendritic cells for enhanced interferon-alpha response. AB - A hallmark of acute classical swine fever is the high interferon (IFN)-alpha levels found in the serum early after infection, followed by an inflammatory cytokine storm. Plasmacytoid dendritic cells (pDCs) represent the only known cell type that produces IFN-alpha upon classical swine fever virus (CSFV) infection in vitro. In primary target cells of the virus the viral protein N(pro) inhibits the induction of type I IFN via the degradation of IRF3. We hypothesized that the early systemic pDC-derived IFN-alpha response sensitizes immune cells for enhanced responsiveness and augment cytokine responses after CSFV infection through the upregulation of IRF7. Therefore, bone marrow-derived granulocyte macrophage-colony stimulating factor (GM-CSF)-induced DCs, were pretreated with IFN-beta or conditioned medium from CSFV-activated enriched pDC, and expression of the pro-inflammatory cytokines interleukin (IL)-1beta, IL-6, and IFN-alpha was assessed after infection with wild-type CSFV and with an N(pro) mutant [N(pro)(D(136)N)] unable to interact with IRF3 and IRF7. While type I IFN treatment sensitized the DCs for enhanced IFN and cytokine responses after stimulation with influenza virus, lipopolysaccharide or poly(I):poly(C), this was not observed for CSFV. In contrast, the N(pro)(D(136)N) mutant CSFV induced elevated IFN-alpha responses in type I IFN-pretreated GM-CSF DCs. These results indicate that CSFV has evolved to prevent type I IFN sensitization in infected cells through the action of the N(pro). PMID- 22313264 TI - Estimating incident population distribution from prevalent data. AB - A prevalent sample consists of individuals who have experienced disease incidence but not failure event at the sampling time. We discuss methods for estimating the distribution function of a random vector defined at baseline for an incident disease population when data are collected by prevalent sampling. Prevalent sampling design is often more focused and economical than incident study design for studying the survival distribution of a diseased population, but prevalent samples are biased by design. Subjects with longer survival time are more likely to be included in a prevalent cohort, and other baseline variables of interests that are correlated with survival time are also subject to sampling bias induced by the prevalent sampling scheme. Without recognition of the bias, applying empirical distribution function to estimate the population distribution of baseline variables can lead to serious bias. In this article, nonparametric and semiparametric methods are developed for distribution estimation of baseline variables using prevalent data. PMID- 22313265 TI - Bioaccumulation and metabolism of polybrominated diphenyl ethers in carp (Cyprinus carpio) in a water/sediment microcosm: important role of particulate matter exposure. AB - Microcosms were built up to simulate a pond system with polybrominated diphenyl ether (PBDE) contaminated sediment and bioorganisms. The microcosms were divided into groups A and B. In group A, both benthic invertebrates (tubificid worms) and carp (Cyprinu carpio) were added, while in group B, only fish were added. After exposure for 20 d, the fish were sampled (exposure I). A net was fixed in the microcosms, and new fish were added (exposure II). These fish were prohibited from contacting the sediment by the net, and the accumulation and depuration of PBDEs in the fish were investigated. Among 11 monitored PBDE congeners (BDE-28, BDE-47, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183, BDE-206, BDE-207, BDE-208, and BDE-209), only 5 congeners (BDE-28, BDE-47, BDE-100, BDE-153, and BDE-154) were detected in the carp fillets and liver. BDE-99 and BDE-183 were not detected in the fish because of the efficient metabolic debromination in carp tissues. The uptake of PBDEs in exposure I was significantly higher/faster than that in exposure II, since the fish in exposure I had an opportunity to take in more of the highly contaminated particles. The uptake kinetics (k(s)) and elimination (k(e)) rate coefficients showed a general trend of decreasing with increasing log K(ow). No significant difference was observed in uptake/depuration kinetics between groups A and B, indicating that the tubificids' reworking does not affect the bioaccumulation of sediment-associated PBDEs in fish significantly. All the PBDE congeners, including nona- and deca-BDEs, were bioaccumulated in the tubificid worms. The PBDE concentrations in the worms were significantly higher than those in the fish, and the congener profile of the sevem major congeners (BDE-28, BDE-47, BDE-99, BDE-100, BDE-153, BDE-154, and BDE-183) was distinctly different from that of fish tissues. The biota-sediment accumulation factors in the worms ranged from 0.01 to 5.89 and declined with increasing bromination and log K(ow.). PMID- 22313266 TI - Occluding effect of Nd:YAG laser and different dentin desensitizing agents on human dentinal tubules in vitro: a scanning electron microscopy investigation. AB - OBJECTIVES: This in vitro study aimed to microscopically evaluate and compare the occluding effect of the Nd:YAG laser and different dentin desensitizing agents on human dentinal tubules. MATERIALS AND METHODS: The Nd:YAG laser (SunLaseTM 800) and four commercially available and professionally applied dentin desensitizers (Gluma(r) desensitizer, Tenure Quick(r), QuellTM desensitizer, and VivaSens(r)) were investigated in this study. Sixty-four extracted intact human molars were used. Each dentin surface was divided by shallow indentation into two halves, one of which was used for treatment and the other of which served as a control. The dentin surfaces were etched to remove any smear plugs and to mimic the open dentinal tubules of sensitive dentin using 0.5 M ethylenediaminetetraacetic acid (pH 7.4) for two minutes (applied with a microbrush) and then rinsed with an air water syringe for 30 seconds. The laser samples (n=16) were randomly divided into four groups of four samples each. These groups were the step-up technique group, the 14-day group, the one-minute group, and the two-minute group. Forty-eight samples were treated with the four tested desensitizing agents and were randomly divided into four groups (n=12/group). Each group was further subdivided into three subgroups (n=4). Samples of the first subgroup were treated for 14 days, while those of the second subgroup were treated once. Samples of the last subgroup were fractured longitudinally after a single treatment. All of the samples were then examined under a scanning electron microscope. RESULTS: The Nd:YAG laser-irradiated dentin showed reduction or complete obliteration of the dentinal tubule lumen; thus, the treatment modified the original dentinal structure. The lased dentin surface in the two-minute group showed bubble-like changes in the area of the dentinal tubules' orifices. Statistically, the two minute group was found to have a significantly higher percentage of partially or fully occluded tubules than did the one-minute group. All of the studied desensitizing agents produced occlusion of the dentinal tubules; however, the appearance of the precipitates, the level of coverage, and the degree of dentinal occlusion varied among the tested products. CONCLUSION: Throughout the specified period of this study, occlusion and/or narrowing of the open dentinal tubules have been successfully achieved with both treatment approaches. PMID- 22313267 TI - Influence of volumetric shrinkage and curing light intensity on proximal contact tightness of class II resin composite restorations: in vitro study. AB - BACKGROUND: Proximal contact tightness of class II resin composite restorations is influenced by a myriad of factors. Previous studies investigated the role of matrix band type and thickness, consistency of resin composite, and technique of placement. However, the effect of volumetric shrinkage of resin and intensity of curing light has yet to be determined. Thus, the aim of this study was to identify the influence of these factors on the proximal contact tightness when restoring class II cavity preparations in vitro. METHODS: Sixty artificial molars were restored with either a low-shrinkage (Filtek Silorane, 3M ESPE) or a conventional (Z100, 3M ESPE) composite and polymerized with low-intensity (Smartlite IQ2, Dentsply) or high-intensity light curing units (Demi(TM), Kerr). Proximal contact tightness was measured using the Tooth Pressure Meter. Data were statistically analyzed using one-way analysis of variance and Tukey post hoc test. RESULTS: Use of low-shrinkage composite (Filtek Silorane) resulted in significantly tighter proximal contacts compared to the use of conventional composite (Z100) when cured with the same polymerization unit (p<0.001). Moreover, the low-intensity curing unit (IQ2) resulted in significantly tighter contacts than the high-intensity unit when material is constant (p<0.001). CONCLUSIONS: Low-shrinkage resin composite and low curing light intensity is associated with tighter proximal contact values. PMID- 22313268 TI - Degree of conversion of simplified contemporary adhesive systems as influenced by extended air-activated or passive solvent volatilization modes. AB - This study evaluated the effect of five methods of solvent volatilization on the degree of conversion (DC) of nine one-bottle adhesive systems using Fourier transform infrared/attenuated total reflectance (FTIR/ATR) analysis. Nine adhesives were tested: Adper Single Bond 2 (SB), Adper Easy One (EO), One Up Bond F Plus (OUP), One Coat Bond SL (OC), XP Bond (XP), Ambar (AM), Natural Bond (NB), GO, and Stae. The adhesive systems were applied to a zinc-selenide pellet and 1) cured without solvent volatilization, 2) left undisturbed for 10 seconds before curing, 3) left undisturbed for 60 seconds before curing, 4) air-dried with an air stream for 10 seconds before curing, and 5) air-dried with an air stream for 60 seconds before curing. FTIR/ATR spectra were obtained, and the DC was calculated by comparing the aliphatic bonds/reference peaks before and after light activation for 10 seconds (FlashLite 1401). The DC means of each material were analyzed by one-way analysis of variance and post hoc Tukey test (p<0.05). The DC of GO and Stae adhesive systems was not affected by the five evaporation conditions. Air-drying for 60 seconds before curing yielded the highest DC for SB, EO, and OC. Extended solvent volatilization time (60 seconds) either with or without air-drying before curing provided the highest DC for AM, NB, XP, and OUP. Thus, the monomer conversion of adhesive systems was material dependent. In general, the 60-second passive or active air-drying modes to volatilize solvents before curing enhanced the degree of conversion for the one-bottle simplified adhesive systems. PMID- 22313269 TI - Composite resin to yttria stabilized tetragonal zirconia polycrystal bonding: comparison of repair methods. AB - PURPOSE: The purpose of the current study was to evaluate different approaches for bonding composite to the surface of yttria stabilized tetragonal zirconia polycrystal (Y-TZP) ceramics. METHODS: One hundred Y-TZP blocks were embedded in acrylic resin, had the free surface polished, and were randomly divided into 10 groups (n=10). The tested repair approaches included four surface treatments: tribochemical silica coating (TBS), methacryloxydecyldihidrogenphosphate (MDP) containing primer/silane, sandblasting, and metal/zirconia primer. Alcohol cleaning was used as a "no treatment" control. Surface treatment was followed by the application (or lack thereof) of an MDP-containing resin cement liner. Subsequently, a composite resin was applied to the ceramic surface using a cylindrical mold (4-mm diameter). After aging for 60 days in water storage, including 6000 thermal cycles, the specimens were submitted to a shear test. Analysis of variance and the Tukey test were used for statistical analyses (alpha=0.05). RESULTS: Surface treatment was a statistically significant factor (F=85.42; p<0.0001). The application of the MDP-containing liner had no effect on bond strength (p=0.1017). TBS was the only treatment that had a significantly positive effect on bond strength after aging. CONCLUSION: Considering the evaluated approaches, TBS seems to be the best surface treatment for Y-TZP composite repairs. The use of an MDP-containing liner between the composite and Y TZP surfaces is not effective. PMID- 22313270 TI - Microleakage resistance of minimally invasive Class I flowable composite restorations. AB - Minimally invasive flowable composite Class I restorations are widely used. However, flowable composites are characterized by low filler contents, modified resin formulations, low moduli of elasticity, low viscosity, generally poor mechanical properties, and decreased long-term stability. The purpose of this study was to compare the microleakage resistance of a wide variety of flowable composites used with their manufacturers' recommended bonding systems to that of a long-used and widely studied microhybrid composite when placed as minimally invasive occlusal restorations. Molar teeth were prepared in a standardized manner, restored, artificially aged, stained, sectioned, evaluated, and analyzed. Microleakage varied substantially, by a whole order of magnitude, among the material groups tested. The control group, a conventional microhybrid composite material, leaked significantly less than all the flowable composite groups. Microleakage varied very slightly among measurement site locations. Tiny microscopic bubbles were seen within many of the flowable composite specimens, as were a few voids. PMID- 22313271 TI - Selective enamel etching: effect on marginal adaptation of self-etch LED-cured bond systems in aged Class I composite restorations. AB - The aim of this study was to evaluate the influence of previous enamel etch and light emitting diode (LED) curing on gap formation of self-etch adhesive systems in Class I composite restorations after thermomechanical aging (TMA). Thus, on 192 human molars, a box-shaped Class I cavity was prepared maintaining enamel margins. Self-etch adhesives (Clearfil SE and Clearfil S3) were used to restore the preparation with a microhybrid composite. Before application of the adhesives, half of the teeth were enamel etched for 15 seconds with 37% phosphoric acid; the other half were not etched. For the photoactivation of the adhesives and composite, three light-curing units (LCUs) were used: one polywave (Ultra-Lume LED 5, UL) and two single-peak (FlashLite 1401, FL and Radii-cal, RD) LEDs. After this, epoxy resin replicas of the occlusal surface were made, and the specimens were submitted to TMA. New replicas were made from the aged specimens for marginal adaptation analysis by scanning electron microscopy. Data were submitted to Kruskal-Wallis and Wilcoxon tests (alpha=0.05). Before TMA, when enamel was etched before the application of S3, no gap formation was observed; however, there were gaps at the interface for the other tested conditions, with a statistical difference (p<=0.05). After TMA, the selective enamel etching previous to the S3 application, regardless of the LCU, promoted higher marginal adaptation compared to the other tested groups (p<=0.05). Prior to TMA, higher marginal integrity was observed, in comparison with specimens after TMA (p<=0.05). With regard to Clearfil SE and Clearfil Tri-S cured with FL, no differences of gap formation were found between before and after aging (5.3 +/- 3.8 and 7.4 +/- 7.5, respectively), especially when the Clearfil Tri-S was used in the conventional protocol. When cured with RD or UL and not etched, Clearfil Tri-S presented the higher gap formation. In conclusion, additional enamel etching promoted better marginal integrity for Clearfil Tri-S, showing it to be an efficient technique for Class I composite restorations. The two-step self-etch adhesive was not influenced by selective enamel etching or by the LED-curing unit. PMID- 22313272 TI - Shear bond strength of different repair systems to titanium after water aging. AB - This study evaluated the shear bond strength (SBS) and stability of commercially pure titanium (CP Ti)/repair material interfaces promoted by different repair systems. One hundred CP Ti cast discs were divided into five repair system groups: 1) Epricord (EP); 2) Bistite II DC (BT); 3) Cojet (CJ); 4) Scotchbond Multi-Purpose Plus (SB) (control group); and 5) Cojet Sand plus Scotchbond Multi Purpose Plus (CJSB). The specimens were stored in distilled water for 24 hours at 37 degrees C, thermal cycled (5000 cycles, 5 degrees -55 degrees C) and stored under the same conditions for either 24 hours or six months (n=10). SBS was tested and the data were analyzed by two-way analysis of variance (ANOVA) and Tukey test (alpha=.05). Failure mode was determined with a stereomicroscope (20*). The repair system, storage time, and their interaction significantly affected the SBS (p<0.001). At 24 hours, CJSB exhibited the highest SBS value, followed by CJ. At six months, these two groups had similar mean SBS (p>0.05) and higher means in comparison to the other groups. For both storage times, BT presented the lowest SBS, while the EP and SB groups did not differ significantly from one another (p>0.05). There were no significant differences in SBS between the storage times for the groups EP and CJ (p>0.05). The groups BT, SB, and CJSB showed 100% adhesive failure, irrespective of storage time. The CJSB group showed the highest SBS at both storage times. At six months, the CJ group exhibited a similar SBS mean value when compared to the CJSB group. Water storage adversely affected the groups BT, SB (control group), and CJSB. Considering SBS values, stability, and the failure mode simultaneously, the CJ group showed the best CP Ti repair performance. PMID- 22313273 TI - Proximal contact tightness between direct-composite additions in the posterior dentition: an in vitro investigation. AB - PURPOSE: The aim of the study was to test whether a novel three-step matrix technique for posterior direct-composite additions creates sufficiently strong proximal contacts. MATERIALS AND METHODS: Contact tightness was measured between direct-composite additions and between original teeth on a model. Therefore, the frictional forces required to remove a straight, 0.05-mm-thick, metal matrix band inserted between adjacent teeth and held by a universal testing machine (Zwicki, Zwick GmbH, Ulm, Germany) were recorded. Measurements were taken at three time points to carry out reference analysis: at baseline, after removal of the maxillary right second premolar (tooth #15) to simulate a diastema, and after closure of the diastema by inserting two direct-composite additions with the three-step matrix technique on the maxillary right first premolar (tooth #14) and first molar (tooth #16). Measurements were performed in the maxillary right (first) and left (second) quadrants to document sagittal displacement. RESULTS: The original contact tightness values were between 1.65 +/- 0.88 N and 3.05 +/- 0.60 N in the first quadrant and between 1.23 +/- 0.51 N and 2.18 +/- 0.43 N in the second quadrant. After removal of tooth 15, values decreased significantly in the first quadrant and insignificantly in the second. After reconstruction, the contact tightness between teeth 14 and 16 was significantly stronger (tighter) (3.20 +/- 0.80 N) than the originally measured contact tightness between teeth 14 and 15 (2.86 +/- 0.64 N) and teeth 15 and 16 (1.65 +/- 0.88 N) (p=0.006 and 0.001, respectively). CONCLUSIONS: Within the limitations of an in vitro investigation, this study has shown that by using a novel, three-step matrix technique, direct posterior composite additions can form sufficiently tight proximal contacts. PMID- 22313274 TI - In vitro and in vivo evaluations of three computer-aided shade matching instruments. AB - This study evaluated the accuracy and reliability of three computer-aided shade matching instruments (Shadepilot, VITA Easyshade, and ShadeEye NCC) using both in vitro and in vivo models. The in vitro model included the measurement of five VITA Classical shade guides. The in vivo model utilized three instruments to measure the central region of the labial surface of maxillary right central incisors of 85 people. The accuracy and reliability of the three instruments in these two evaluating models were calculated. Significant differences were observed in the accuracy of instruments both in vitro and in vivo. No significant differences were found in the reliability of instruments between and within the in vitro and the in vivo groups. VITA Easyshade was significantly different in accuracy between in vitro and in vivo models, while no significant difference was found for the other two instruments. Shadepilot was the only instrument tested in the present study that showed high accuracy and reliability both in vitro and in vivo. Significant differences were observed in the L*a*b* values of the 85 natural teeth measured using three instruments in the in vivo assessment. The pair-agreement rates of shade matching among the three instruments ranged from 37.7% to 48.2%, and the incidence of identical shade results shared by all three instruments was 25.9%. As different L*a*b* values and shade matching results were reported for the same tooth, a combination of the evaluated shade matching instruments and visual shade confirmation is recommended for clinical use. PMID- 22313275 TI - Clinical evaluation of a low-shrinkage composite in posterior restorations: one year results. AB - OBJECTIVES: The aim of this study was to compare the one-year clinical performance of three restorative systems, which included a novel low-shrinkage composite and two bonding strategies. MATERIALS AND METHODS: Twenty-five patients received three Class I (occlusal) or Class II restorations performed with one of three restorative systems: Filtek Silorane Restorative System (FS); Adper Scotchbond 1 XT, a two-step etch-and-rinse adhesive, with Filtek Z250 (XT); and Adper Scotchbond SE, a two-step self-etch adhesive, with Filtek Z250 (SE). All materials were applied following the manufacturer's instructions. Two independent observers evaluated the restorations at baseline, after six months, and after one year, according to the United States Public Health System modified criteria. The Kruskal-Wallis test and the Mann-Whitney U-test were computed to compare the behavior of the restorative systems; Friedman and Wilcoxon tests were used to analyze the intrasystem data (alpha=0.05). RESULTS: All restorations were evaluated at one year. FS and XT performed statistically similarly at one year, but marginal staining for SE was statistically worse. Intrasystem comparisons between baseline and one year also showed deterioration of marginal staining for SE, while a deterioration of the marginal adaptation was recorded for both SE and FS. XT was the only system for which there was no statistical change of the parameters measured in this study. CONCLUSIONS: Both restorative systems using self-etch adhesives showed a tendency to degradation of marginal adaptation after one year of clinical use, compared to baseline values. Although the clinical performance of FS was deemed acceptable after one year, this study did not find any advantage of the silorane-based composite over the methacrylate-based composite. The low-shrinkage associated with FS may not be a determinant factor for clinical success. PMID- 22313276 TI - Clinical evaluation of stress-reducing direct composite restorations in structurally compromised molars: a 2-year report. AB - OBJECTIVE: To evaluate the clinical performance of class II large-size direct composite restorations. MATERIALS AND METHODS: Fifty (50) patients 18 years or older were included in this clinical trial restoring 75 vital molar teeth with large-size cavities. INCLUSION CRITERIA: Occlusal extension greater than two thirds the intercuspal distance and proximal extension greater than half the distance between line angles. Teeth with residual cavity walls less than 1 mm and with one or more cusps involved were excluded. Teeth were randomly divided in three groups. Group 1: Opti-Bond FL; group 2: Scotchbond 1 XT; group 3: PQ1. Total-etching was performed using 35% phosphoric acid followed by the application of 2% chlorhexidine gluconate in the three groups. All teeth were restored using Vit-l-escence microhybrid composite resin. The proximal surface was built up first, followed by dentin and enamel occlusal surface stratification; wedge shaped increments of composite resin were placed and cured using the UltraLume V curing light through a combination of pulse and progressive curing techniques. RESULTS: Restorations were evaluated at six-month intervals during the two-year period using a modified US Public Health Service criteria by two independent evaluators precalibrated at 85% reliability. No failures were reported and alpha scores were recorded for all parameters. Statistical analysis was performed using a chi(2) test and the Fisher exact test (chi(2)=10.6; p=0.001). No teeth exhibited sensitivity in the three groups both at the two-week recall and two year follow-up. PMID- 22313277 TI - Cervical margin integrity of Class II resin composite restorations in laser- and bur-prepared cavities using three different adhesive systems. AB - One of the challenges in durability of posterior tooth-colored restorative materials is polymerization shrinkage, which results in gap formation between the restoration and tooth structure. The aim of the present study was to investigate marginal adaptation of Class II composite restorations using a self-etching and two etch-and-rinse adhesive systems in cavities prepared either with bur or Er,Cr:YSGG laser. A total of 45 extracted sound human premolars were selected. In each tooth, mesial and distal Class II cavities were prepared either by a diamond bur or by Er,Cr:YSGG laser with the margins 1 mm apical to the cemento-enamel junction. Then the teeth were randomly divided into three groups of 15 each, according to the type of the adhesive system used (Single Bond, Single Bond 2, and Adper Easy One adhesive systems). Subsequent to restoring the teeth, the specimens were subjected to thermal cycling between 5 +/- 2 degrees C and 55 +/- 2 degrees C for 500 cycles and were then cut longitudinally into two halves using a diamond disk. Marginal adaptation was evaluated using a stereomicroscope, and the values for gap widths were obtained in micrometers. Data were analyzed using two-factor analysis of variance and post hoc tests. There were statistically significant differences in mean marginal gap widths between the adhesive type and preparation groups (p<0.05). The interfacial gap width in bur-prepared cavities was significantly less than that in laser-prepared cavities, and the lowest gap width was observed in Adper Easy One regardless of the type of the preparation. PMID- 22313279 TI - Verifying occlusal reduction during tooth preparation. PMID- 22313278 TI - Effect of composite insertion technique on cuspal deflection using an in vitro simulation model. AB - OBJECTIVE: The objective of this study was to investigate, by simulation, the effect of conventional composite resin insertion techniques on cuspal deflection using bonded typodont artificial teeth. The deflection produced by a new low shrinkage composite was also determined. MATERIALS AND METHODS: Sixty standardized MOD preparations on ivorine maxillary premolars were prepared: group A at 4 mm depth and group B at 6 mm depth. Each group was further subdivided according to composite insertion technique (n=6), as follows: 1) bulk insertion, 2) horizontal increments, 3) tangential increments, and 4) a modified tangential technique. Preparations were microetched, acid-cleaned, and bonded with adhesive resin to provide micromechanical attachment before restoration with a conventional composite (Spectrum TPH( 3 ), Dentsply). Two additional subgroups at 4 mm and 6 mm depth (n=6) were restored in bulk using low-shrinkage composite (Filtek LS, 3M/ESPE). All groups received the same total photo-polymerization time. Cuspal deflection was measured during the restorative procedure using two Linear Variable Differential Transformers attached to a data acquisition system. RESULTS: The average cuspal deflections for group A were 1) 40.17 +/- 1.18 MUm, 2) 25.80 +/- 4.98 MUm, 3) 28.27 +/- 5.12 MUm, and 4) 27.33 +/- 2.42 MUm. The deflections in group B were 1) 38.82 +/- 3.64 MUm, 2) 50.39 +/- 9.17 MUm, 3) 55.62 +/- 8.16 MUm, and 4) 49.61 +/- 8.01 MUm. Cuspal flexure for the low shrinkage composite was 11.14 +/- 1.67 MUm (group A: 4 mm depth) and 16.53 +/- 2.79 MUm (group B: 6 mm depth). CONCLUSIONS: All insertion techniques using conventional composite caused cuspal deformation. In general, deeper preparations showed increased cuspal deflection-except in the case of bulk insertion, which was likely affected by decreased depth of cure. Cuspal movement using low shrinkage composite was significantly reduced. PMID- 22313280 TI - Caries-preventive activity of fluoride-containing resin-based desensitizers. AB - OBJECTIVE: The purpose of this study was to evaluate the effects of different desensitizing agents on the prevention of root caries when applied to root surfaces. MATERIALS AND METHODS: Thirty human roots were sectioned into quarters with a 3 * 4 mm window. A desensitizer (VX, ClinproTM XT Varnish; SP, Seal & Protect(r); or PB, ClearfilTM Protect Bond) was applied to three of the quarters in each window. Teeth were stored separately in water for one day, 30 days, or 60 days. The remaining quarter, without the application of desensitizer, served as a control. After storage in water, all specimens were subjected to pH cycling. Scanning electron microscopy was used to observe the demineralization bands created on the subsurface layer. The weight percentages of fluorine (F), silica, and calcium (Ca) were determined using electron probe microanalysis to quantify the elemental distributions in the root dentin. The concentrations of F released during a pH cycling were measured. RESULTS: For the control group, the average lesion depth was 18.92 +/- 5.42 MUm, and the average Ca loss was 15.66% +/- 6.80% in the superficial layer and 30.44% +/- 9.61% in the subsurface layer. No Ca loss occurred in the desensitizer-treated groups. All desensitizing agents remained intact for at least 60 days. F levels were increased in the hybrid layer but not in the subhybrid area. Outward release of F diminished with time. CONCLUSION: The F-containing resin-based desensitizers protected exposed root surfaces from demineralization. F liberated from the desensitizers was detected only at minimal levels. PMID- 22313281 TI - A simplified technique for restoring interproximal root surface lesions. PMID- 22313282 TI - Effect of ceramic veneer opacity and exposure time on the polymerization efficiency of resin cements. AB - The objective of this study was to determine the degree of conversion (DC), hardness (H), and modulus of elasticity (E) of a dual-cured resin cement, a light cured resin cement, and a flowable resin cured through opaque or translucent ceramic with different exposure times. RelyX ARC (dual), RelyX Veneer (light cured), and Filtek Z350 Flow resin specimens 0.5 mm thick were cured for 40, 80, and 120 seconds through 1-mm thick translucent or opaque feldspathic ceramic disks (n=10). The specimens were stored at 37 degrees C for 24 hours. Half of each specimen was used to test the DC and the other half to test H and E. The DC was determined in a Fourier transform infrared spectrometer in absorbance mode at peaks of 1638 cm(-1) and 1610 cm(-1). H and E were determined using nanoindentation with one loading cycle and a maximum load of 400 mN. The data were analyzed with three-way analysis of variance (ANOVA), the Games-Howell test, and the Pearson correlation test (alpha=0.05). Statistically significant differences were found for all three factors (material, opacity, and exposure time), as well as interaction between them. The opaque ceramic resulted in lower DC, H, and E than the translucent ceramic for an exposure time of 40 seconds. An exposure time of 120 seconds resulted in a similar DC for all materials, irrespective of the opacity of the ceramic. Materials cured for 120 seconds had higher H and E than those cured for 40 seconds. The exposure time and opacity of the ceramic exerted an influence on the DC, H, and E of the materials evaluated. PMID- 22313283 TI - Clinical trials and biomarker research on lung cancer in China. AB - INTRODUCTION: Over the past 10 years, there have been significant advances in clinical trials and translation research on lung cancer in China. These advances have changed the clinical practice of lung cancer treatment. Translation research has clarified many molecular mechanisms of lung cancer development, growth and metastasis. Based on these results, a few cancer-driving molecular targets were identified. Many new compounds that directly or indirectly target these driver genes have been developed and tested. AREAS COVERED: Studies from the literature and ongoing work from the author's group were reviewed. This was with the aim of outlining the current state of a clinical trial cooperative group for lung cancer and highlighting some important clinical trials and biomarker research that have changed lung cancer clinical practice in China. EXPERT OPINION: For biomarker driven clinical research, it is important to identify subgroups of patients who are most likely to benefit from given targeted therapies. In this setting, the rapid identification and translation of validated biomarkers will be integral to the treatment of lung cancer. It is also important to utilize results from high quality clinical research groups to enrich patients lives and to perform these challenging clinical trials. PMID- 22313284 TI - Cyril Clarke and the prevention of rhesus haemolytic disease of the newborn. AB - Cyril Clarke was an outstanding general physician and lepidopterist. Late in his career, and stimulated by his work on the genetics of mimicry in butterflies, he became interested in the evolving field of medical genetics. His work on the relationship of blood groups to particular diseases led him and his team in Liverpool to evolve a remarkably successful approach to the prevention of Rhesus haemolytic disease of the newborn. PMID- 22313285 TI - Nanoplasmonics: classical down to the nanometer scale. AB - We push the fabrication limit of gold nanostructures to the exciting sub nanometer regime, in which light-matter interactions have been anticipated to be strongly affected by the quantum nature of electrons in metals. Doing so allows us to (1) evaluate the validity of classical electrodynamics to describe plasmonic effects at this length scale and (2) witness the gradual (instead of sudden) evolution of plasmon modes when two gold nanoprisms are brought into contact. Using electron energy-loss spectroscopy and transmission electron microscope imaging, we investigated nanoprisms separated by gaps of only 0.5 nm and connected by conductive bridges as narrow as 3 nm. Good agreement of our experimental results with electromagnetic calculations and LC circuit models evidence the gradual evolution of the plasmonic resonances toward the quantum coupling regime. We demonstrate that down to the nanometer length scales investigated classical electrodynamics still holds, and a full quantum description of electrodynamics phenomena in such systems might be required only when smaller gaps of a few angstroms are considered. Our results show also the gradual onset of the charge-transfer plasmon mode and the evolution of the dipolar bright mode into a 3lambda/2 mode as one literally bridges the gap between two gold nanoprisms. PMID- 22313286 TI - Quantification of transcription factor binding in cell extracts using an electrochemical, structure-switching biosensor. AB - Transcription factor expression levels, which sensitively reflect cellular development and disease state, are typically monitored via cumbersome, reagent intensive assays that require relatively large quantities of cells. Here, we demonstrate a simple, quantitative approach to their detection based on a simple, electrochemical sensing platform. This sensor sensitively and quantitatively detects its target transcription factor in complex media (e.g., 250 MUg/mL crude nuclear extracts) in a convenient, low-reagent process requiring only 10 MUL of sample. Our approach thus appears a promising means of monitoring transcription factor levels. PMID- 22313288 TI - Regulation of the isophthalate catabolic operon controlled by IphR in Comamonas sp. strain E6. AB - The isophthalate (IPA) catabolic operon (iphACBDR) of Comamonas sp. strain E6 responsible for the conversion of IPA into protocatechuate is negatively regulated by an IclR-type transcriptional regulator, IphR. Promoter analysis showed that the region sufficient for the IPA-dependent induction of the iphA promoter was located within the 87 bp region upstream from the iphA start codon. The transcription start site of the iph operon was mapped at a cytosine located 49 bp upstream of the iphA start codon. Two inverted repeat sequences IR1 (positions -21 to -7 relative to the iphA transcription start site) and IR2 (-2 to +10) were found in the binding region of IphR identified by electrophoretic mobility shift assays (EMSA) using purified IphR. Mutation analysis of each half site of these inverted repeat sequences indicated that both IR2 and a downstream half-site of IR1 are necessary for the binding of IphR. EMSA in the presence of IPA or its analogous substrates demonstrated that IPA had the ability to inhibit the binding of IphR to this operator region. In conclusion, the iph operon is negatively autoregulated by the binding of IphR to the operator region, and this repression is released by the presence of IPA. PMID- 22313287 TI - Acupuncture compared with oral antihistamine for type I hypersensitivity itch and skin response in adults with atopic dermatitis: a patient- and examiner-blinded, randomized, placebo-controlled, crossover trial. AB - BACKGROUND: Itch is the major symptom of atopic dermatitis (AD). Acupuncture has been shown to exhibit a significant effect on experimental itch in AD. Our study evaluated acupuncture and antihistamine itch therapy (cetirizine) on type I hypersensitivity itch and skin reaction in AD using a patient and examiner blinded, randomized, placebo-controlled, crossover trial. METHODS: Allergen induced itch was evaluated in 20 patients with AD after several interventions in separate sessions: preventive (preceding) and abortive (concurrent) verum acupuncture (VAp and VAa), cetirizine (10 mg, VC), corresponding placebo interventions (preventive, PAp, and abortive, PAa, placebo acupuncture; placebo cetirizine pill, PC) and a no-intervention control (NI). Itch was induced on the forearm and temperature modulated over 20 min, using our validated model. Outcome parameters included itch intensity, wheal and flare size and the D2 attention test. RESULTS: Mean itch intensity (SE: 0.31 each) was significantly lower following VAa (31.9) compared with all other groups (PAa: 36.5; VC: 36.8; VAp: 37.6; PC: 39.8; PAp: 39.9; NI: 45.7; P < 0.05). There was no significant difference between VAp and VC (P > 0.1), although both therapies were significantly superior to their respective placebo interventions (P < 0.05). Flare size following VAp was significantly smaller (P = 0.034) than that following PAp. D2 attention test score was significantly lower following VC compared with all other groups (P < 0.001). CONCLUSIONS: Both VA and cetirizine significantly reduced type I hypersensitivity itch in patients with AD, compared with both placebo and NI. Timing of acupuncture application was important, as VAa had the most significant effect on itch, potentially because of counter irritation and/or distraction. Itch reduction following cetirizine coincided with reduced attention. PMID- 22313289 TI - Silver nanoparticles: influence of stabilizing agent and diameter on antifungal activity against Candida albicans and Candida glabrata biofilms. AB - AIM: The purpose of this work was to evaluate the size-dependent antifungal activity of different silver nanoparticles (SN) colloidal suspensions against Candida albicans and Candida glabrata mature biofilms. METHODS AND RESULTS: The research presented herein used SN of three different average sizes (5, 10 and 60 nm), which were synthesized by the reduction of silver nitrate through sodium citrate and which were stabilized with ammonia or polyvinylpyrrolidone. Minimal inhibitory concentration (MIC) assays were performed using the microdilution methodology. The antibiofilm activity of SN was determined by total biomass quantification (by crystal violet staining) and colony forming units enumeration. MIC results showed that all SN colloidal suspensions were fungicidal against the tested strains at very low concentrations (0.4-3.3 MUg ml(-1) ). With regard to biomass quantification, SN colloidal suspensions were very effective only against C. glabrata biofilms, achieving biomass reductions around 90% at a silver concentration of 108 MUg ml(-1) . In general, all SN suspensions promoted significant log(10) reduction of the mean number of cultivable biofilm cells after exposure to silver concentrations at or higher than 108 MUg ml(-1) . Moreover, the results showed that the particle size and the type of stabilizing agent used did not interfere in the antifungal activity of SN against Candida biofilms. CONCLUSIONS: This study suggests that SN have antifungal therapeutic potential, but further studies are still required namely regarding formulation and delivery means. SIGNIFICANCE AND IMPACT OF THE STUDY: SN may contribute to the development of new strategies for the improvement of oral health and quality of life particularly of the complete denture wearers. PMID- 22313290 TI - Multilevel functional clustering analysis. AB - In this article, we investigate clustering methods for multilevel functional data, which consist of repeated random functions observed for a large number of units (e.g., genes) at multiple subunits (e.g., bacteria types). To describe the within- and between variability induced by the hierarchical structure in the data, we take a multilevel functional principal component analysis (MFPCA) approach. We develop and compare a hard clustering method applied to the scores derived from the MFPCA and a soft clustering method using an MFPCA decomposition. In a simulation study, we assess the estimation accuracy of the clustering membership and the cluster patterns under a series of settings: small versus moderate number of time points; various noise levels; and varying number of subunits per unit. We demonstrate the applicability of the clustering analysis to a real data set consisting of expression profiles from genes activated by immunity system cells. Prevalent response patterns are identified by clustering the expression profiles using our multilevel clustering analysis. PMID- 22313291 TI - Synthetic peptide-conjugated titanium alloy for enhanced bone formation in vivo. AB - There are growing demands for bioactive titanium implants that could shorten the healing period, promote faster rehabilitation, and thereby increase the success rate of treating patients with poor bone quality. A synthetic receptor-binding peptide mimicking bone morphogenetic protein-2 (BMP-2) was covalently linked to a titanium alloy with two types of topography--machined (TiMA) and rough (TiGB)--by using a chemical conjugation process. In vivo osseointegration capacity was evaluated chronologically using histomorphometric analysis at 2, 4, and 8 weeks after implantation in the distal femurs of rabbits. In the histologic examinations, peri-implant bone formation was more active around TiGB than TiMA. Compared to the control groups (nonconjugated TiMA and TiGB) at 2, 4, and 8 weeks, the peptide-conjugated groups (TiMA-P and TiGB-P) had more mature new bone, thicker trabeculae, more rapid bone maturation, and higher affinity index (percentage of new bone contact length) in histomorphometric analysis. Particularly, differences in the affinity index between the peptide-conjugated and nonconjugated groups were more pronounced at the early phase of peri-implant healing (2 and 4 weeks). However, at 8 weeks, enhanced bone formation was less prominent according to peptide conjugation, especially in specimens with a rough surface. The titanium alloys in the rabbit femurs led to a significant increase of bone growth when modified with bioactive peptides, especially during the early phase of bone healing. These results confirm that biochemical modifications of titanium surfaces can enhance the rate of bone healing compared with that of untreated titanium surfaces. PMID- 22313292 TI - Analysis of the alpha-glucosidase inhibitory activity of chromenone derivatives based on their molecular features: a computational study. AB - alpha-Glucosidase is one of the important enzymes in glucose digestion and its inhibitors are known to possess a large number of therapeutic effects. In this present investigation, we have performed structural feature analysis of some of these inhibitors namely, chromenone derivatives using the Molecular Operating Environment (MOE) software. The results of the QSAR study show that the derived models are statistically significant and were validated by external (test set) and internal (leave one out) methods. The crossvalidated correlation coefficients (Q2) of the models show that the training and test sets have the values > 0.6687. The physicochemical descriptors contributed for the models building in training set and complete data set show that the log of aqueous solubility (LogS) and the molar refractivity on the van der Waals surface area of the molecules (SMR_VSA4) positively contributed for the inhibitory activity. Further, the study also reveals that the polarizability and hydrogen bond acceptor/donor groups are important for the alpha-glucosidase inhibitory activity and these results are in agreement with the earlier studies obtained in our laboratory on alpha glucosidase inhibitors which have shows that the polar surface area of the molecule is important for the interaction. The pharmacophore contours of the molecule also showed the importance of the polar surface property on the molecules. This computational analysis will help in the development of novel alpha-glucosidase inhibitors for various diseases. PMID- 22313293 TI - Synthesis and bioactivities of 2-azetidinone derivatives as cholesterol absorption inhibitors. AB - Twenty-four 2-azetidinone derivatives have been designed and synthesized as cholesterol absorption inhibitors. All new compounds were evaluated for their activity to inhibit cholesterol absorption in hamsters, and most of them showed considerable effects in lowering the levels of total cholesterol in the serum, especially compound 2d, 4a, 4f, 4i and 4j. PMID- 22313294 TI - 3D-QSAR of novel phosphodiesterase-4 inhibitors by genetic function approximation. AB - Phosphodiesterase-4 (PDE 4) enzyme has emerged as an invaluable target for the treatment of asthma, chronic obstructive pulmonary disease and rheumatoid arthritis. These findings have generated widespread interest in PDE-4 inhibitors as a potential molecular target for the development of new anti-inflammatory drugs. A series of N-substituted cis-tetra- and cis-hexahydrophthalazinone derivatives have been reported as novel, selective PDE-4 inhibitors with potent anti-inflammatory activity. In order to gain further insights into the structural requirements of novel series of N-substituted cis-tetra and cis hexahydrophthalazinone derivatives as PDE-4 inhibitors, a three-dimensional quantitative structure activity relationship (3D-QSAR) was performed using Genetic Function Approximation (GFA). The QSAR model was generated using a training set of 45 molecules and the predictive ability of the resulting each model was assessed using a test set of 9 molecules. The internal and external consistency of final QSAR model was 0.675 and 0.750 respectively. Analysis of results from the present QSAR study indicates that shape and structural descriptors strongly govern the PDE-4 enzyme inhibitory activity. This QSAR study highlights the structural features required for PDE-4 enzyme inhibition and may be useful for design of potent PDE-4 inhibitors. PMID- 22313295 TI - A QSAR study on some series of HIV-1 integrase inhibitors. AB - A quantitative structure-activity relationship (QSAR) study has been made on a series of 4-chloro-N-(4- oxopyrimidin-2-yl)-2-mercaptobenzenesulfonamides. The activities of the compounds were reported against 3'-processing and the strand transfer processes catalyzed by the enzyme HIV-1 integrase. By a multiple regression, the activity against 3'-processing is found to be significantly correlated with hydrophobic and surface tension properties of the molecules and that against strand transfer with only hydrophobic property of the molecules and an indicator variable. Thus the results indicate that the hydrophobic property of the molecule plays a crucial role in the inhibition of both the 3'-processing and the strand transfer processes. The surface tension of the molecule is also shown to have some effect on inhibition of 3'- processing. PMID- 22313296 TI - Syntheses of 2,3-diarylated 2H-benzo[e][1,2]thiazine 1,1-dioxides and their 3,4 dihydro derivatives, and assessment of their inhibitory activity against MCF-7 breast cancer cells. AB - A practical synthesis of 2,3-diarylated 2H-benzo[e][1,2]thiazine 1,1-dioxides and their 3,4-dihydro derivatives was developed. ortho-Methyl lithiation of N-aryl-o toluenesulfonamide followed by reaction with aryl aldehydes gave carbinol sulfonamides, which were either converted directly, or first oxidized to their ketones and converted, to 2,3-diarylated six-membered benzosultams via a TMSCl NaI-MeCN mediated cyclization. A library of benzosultams was synthesized and evaluated for inhibitory activity against MCF-7 cells. Compound 3 in the 3,4 dihydro (saturated) series and compound 8 in the unsaturated series exhibited the highest potencies with growth inhibition (GI50) values of 0.8 and 18.0 MUM, respectively. Molecular modeling studies suggest that these compounds can associate with the colchicine binding site on microtubules. However, experimental assessments of that and other mechanistic possibilities are still ongoing. PMID- 22313297 TI - Synthesis of 2,4,6-trichlorophenyl hydrazones and their inhibitory potential against glycation of protein. AB - 2,4,6-Trichlorophenyl hydrazones 1-35 were synthesized and their in vitro antiglycation potential was evaluated. Compounds 14 (IC50 = 27.2 +/- 0.00 MUM), and 18 (IC50 = 55.7 +/- 0.00 MUM) showed an excellent activity against glycation of protein, better than the standard (rutin, IC50 = 70 +/- 0.50 MUM). This study thus identified a novel series of antiglycation agents. A structure-activity relationship has been studied, and all the compounds were characterized by spectroscopic techniques. PMID- 22313298 TI - Pharmacophoric modeling and atom-based 3D-QSAR of novel 1-aryl-3-(1-acylpiperidin 4-yl) urea as human soluble epoxide hydrolase inhibitors (sEHIs). AB - Soluble Epoxide Hydrolase (sEH) is an important and promising new pharmacologic target for the treatment of acute systemic inflammation. Inhibition of sEH by a highly selective and potent sEH inhibitor (sEHI) elevates the epoxyeicosatrienoic acids (EETs) level in vivo leading to decreased inflammation. To explore the necessary structural requirement of 1, 3-disubstituted ureas as sEH inhibitors for anti-inflammatory activity, the molecular modeling studies have been pursued. A ligand-based pharmacophoric model and atom-based 3D-QSAR have been generated by Phase. Binding interaction as determined by the docking study revealed that these inhibitors interact at active site (ASP 335 & TYR 383) of sEH enzyme. The pharmacophore model was further used as a 3D query for virtual screening to retrieve potential inhibitors. PMID- 22313299 TI - Synergism from combination of cisplatin and multicentred platinums coded as DH6Cl and TH1 in the human ovarian tumour models. AB - Development of drug resistance and the presence of dose-limiting side-effects remain the two main problems in cancer chemotherapy. Combination of drugs with different mechanisms of action can offer a distinct advantage over monotherapy in overcoming drug resistance and reducing the side-effects. In this study synergism in activity from the combinations of cisplatin (Cis) with two multicentred platinum complexes coded as TH1 and DH6Cl in the human ovarian A2780, A2780cisR and A27800473R cancer cell lines had been investigated. Although Cis, TH1 and DH6Cl all bind with nucleobases in the DNA, they differ in the nature of adducts formed and the non-covalent interactions they may undergo. Whereas Cis binds with nucleobases in the DNA forming mainly intrastrand bifunctional adducts such 1,2 Pt(GG) and 1,2-Pt(AG), TH1 and DH6Cl are expected to form mainly interstrand bifunctional G-Pt.....Pt-G adducts with the DNA. It was found that Cis in combination with TH1 and DH6Cl produced both sequence- and concentration dependent synergism. Generally greater synergism was produced when the two compounds were added at the same time than with a 4 h time gap. For the combination of Cis with TH1, significant synergism was produced only in the parent A2780 cell line but not in the resistant A2780(cisR) and A2780(0473R) cell lines, thus indicating that the combinations of Cis with TH1 would not offer any advantage in overcoming the drug resistance. In contrast, 0/0 h and 4/0 h combinations of Cis and DH6Cl in A2780(cisR) cell line were found to be synergistic, thus indicating that combinations of Cis with DH6Cl may offer a therapeutic advantage. Although both TH1 and DH6Cl are expected to form a number of long-range interstrand G-Pt......Pt-G adducts with nucleobases in the DNA, TH1 and DHCl are expected to differ in their non-covalent interactions with the DNA due to the presence of two 3-hydroxypyridine ligands bound to the central metal ion in TH1 but not in DH6Cl which instead contains two ammino ligands bound to the central palladium ion. PMID- 22313300 TI - Novel 3-(2-(3-methyl-5-substituted-phenyl-4,5-dihydropyrazol-1-yl)-2-oxoethoxy)-2 substituted-phenyl-4H-chromen-4-one: synthesis and anticancer activity. AB - Ten novel 3-(2-(3-methyl-5-substituted-phenyl-4,5-dihydropyrazol-1-yl)-2-oxo ethoxy)-2-substituted-phenyl-4H-chromen-4-one derivatives were synthesized and characterized by 1H NMR and 13 C NMR. All of the compounds have been screened for their anticancer activity. The bioassay tests show that compound 6af exhibited potentially high activity against human gastric cancer cell SGC-7901 with IC50 value of 4.01+/-0.97 MUg/mL. Also, the title compounds were assayed for telomerase inhibition. The results show that compounds 6cf, 6af can strongly inhibit telomerase with IC50 values of 4.89+/-0.11 and 5.02+/-0.91 MUM, respectively. Docking simulation was performed to position compound 6cf into the telomerase (3DU6) active site to determine the probable binding model. PMID- 22313301 TI - Synthesis and antitubercular activity of new L-serinyl hydrazone derivatives. AB - A series of 32 L-serinyl hydrazone derivatives have been synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv, being also evaluated their cell viabilities in non infected and infected macrophages with Mycobacterium bovis Bacillus Calmette-Guerin (BCG). The compounds 8c, 8e, 8h and 8i, were non-cytotoxic and exhibited an important minimum inhibitory concentration (MIC) activity between 25 and 100 MUg/mL, which can be compared with that of the tuberculostatic drug D-cicloserine (5-20 MUg/mL). PMID- 22313302 TI - Design, synthesis and antitumor activity of novel D-glucuronic acid derivatives. AB - A series of D-glucuronic acid derivatives were chemically synthesized including acetylated and deacetylated glucuronamides, as well as N-glucuronides starting from the D-glucuronic acid itself by means of protection/deprotection, activation and condensation protocols. Structure elucidation of all products along with optimization of the synthetic steps is described. The synthesized compounds were evaluated for their in vitro antitumor activity against MCF-7, TK-10 and UACC-62 cell lines. The compounds 4, 5, 7, 8, 14, 16 and 18 were the most active against TK-10 cell line. On the other hand, the most active compounds against the MCF-7 cell line were 9, 18 and 20. However, compounds 7-10 13-15 and 17 were the most active against the UACC-62 cell line. PMID- 22313303 TI - Free radical scanvenging and antioxidant effects of some anthraquinone derivatives. AB - In this study, the screening of five anthraquinones (purpurin, xanthopurpurin, rubiadin, kermisic acid and flavokermisic acid), for their free radical scavenging and antioxidant effects was carried out, using three complementary methods. DPPH (2,2'-diphenyl-1-picrylhydrazyl) revealed that purpurin has a scavenging effect with IC50 = 3.491 +/- 0.014 ug/ml. Results of beta carotene/linoleic acid assay showed that kermisic and flavokermisic acids have significant inhibition of lipid peroxidation with I % = 76.1 +/- 1.5% and 68.6 +/ 2.5%, respectively. In addition, the ferrous ion chelating test showed that only purpurin, with small concentrations, interferes in a dose dependant manner with the formation of Fe2+-ferrozine complex. These results are promising for further studies of the biological and pathological effects of these natural products. PMID- 22313304 TI - MIA-QSAR coupled to different regression methods for the modeling of antimalarial activities of 2-aziridinyl and 2,3-bis-(aziridinyl)-1,4-naphtoquinonyl sulfate and acylate derivatives. AB - The antimalarial activities of a series of 2-aziridinyl and 2,3-bis-(aziridinyl) 1,4-naphtoquinonyl sulfate and acylate derivatives have been modeled using multivariate image analysis (MIA) descriptors. The two-dimensional chemical structures correlated reasonably well with dependent variables (Y block) through partial least squares--PLS (for the unfolded data) and multilinear partial least squares--N-PLS (for the three-way array). However, the use of PCA-ranking as variable selection method and least-squares support vector machines (LS-SVM) as regression method improved significantly the prediction ability of the model. All models were validated through leave-one-out and leave-25%-out cross-validations, as well as by means of a Y-randomization test, and demonstrated advantages in prediction performance over an existing model, in which descriptors related to physicochemical and geometric properties of molecules were used to derive multiple linear regression (MLR) and artificial neural networks (ANN) based models. Accounting for non-linearity seems to be an important task for the QSAR modeling of bioactivities of the studied antimalarial compounds. PMID- 22313305 TI - In silico designing and screening of lead compounds to NS5-methyltransferase of dengue viruses. AB - Ribavirin and its 553 analogues have been docked with NS5-methyltransferase of Dengue viruses using Glide-HTVS and Glide-XP computational tools and the compounds have been screened based on their Glide-Gscores to identify lead ribavirin analogues that may act as inhibitors to the enzyme. Upon studying the interactions of ribavirin triphosphate (RTP) and triphosphate of lead ribavirin analogues with NS5-methyltransferase and Janus tyrosine Kinase-2 (JAK2) enzymes using molecular docking and dynamic methods, the possible mechanism by which the ribavirin causes haemolytic anaemia has been proposed. De novo RTP-analogues showing stronger affinities with NS5-methyltransferase and weaker affinities with JAK2 have been designed. The essential structural features of the de novo RTP analogues for developing them as specific antiviral drugs against the infections due to dengue viruses have been discussed in detail. PMID- 22313306 TI - Synthesis of novel 8-hydroxy quinolin based 1,3,4-oxadiazoles and S-substituted 1,2,4-triazole derivatives and evaluation of their anti-inflammatory, analgesic, ulcerogenic and anti-microbial activities. AB - A series of novel 2-[4-aryl-5-{(quinolin-8-yloxy)methyl}-4H-1,2,4-triazol-3 ylthio]-1-arylethanones (6a-6j) and 8-{(5-aryl-1,3,4-oxadiazol-2 yl)methoxy}quinolines (7a-7d) were synthesized from the corresponding 4-arnyl-1 (2- quinolin-8-yloxy)acetyl) thiosemicarbazides (4a-4d) and hydrazides (3) respectively. The prepared compounds were screened for their anti-inflammatory, analgesic, ulcerogenic and antimicrobial activities. The anti-inflammatory activities were determined by carrageenan induced rat paw edema method. Compounds 6c, 6d, 6f 6j, 7b and 7e significantly inhibited the rat paw edema depending upon the dose employed. These compounds exhibited insignificant ulceration compared to the standard drug Indomethacin. The compounds were also evaluated for their in vitro antimicrobial activity. Some compounds have shown moderate to good activity whereas compound 7b has shown significant zone of inhibition compared to the standard drug Ampicillin against gram negative microorganisms. PMID- 22313307 TI - Antibacterial activity of thyme and lavender essential oils. AB - Strong antiseptic activity of essential oils has been known for a long time. The antibacterial activity of oils was tested against clinical bacterial strains of Staphylococcus, Enterococcus, Escherichia and Pseudomonas genera. The agar diffusion method was used for microbial growth inhibition at various concentrations of the oils from T. vulgaris and L. angustifolia. Susceptibility testing to antibiotics and chemotherapeutics was carried out using disc-diffusion method. 120 strains of bacteria isolated from patients with infections of oral cavity, respiratory, genitourinary tracts and from hospital environment were investigated. The results of experiments showed that the oil from T. vulgaris exhibited extremely strong activity against all of the clinical strains. Thyme oil demonstrated a good efficacy against antibiotics resistant strains of the tested bacteria. Lavender oil has been less activity against clinical strains of Staphylococcus, Enterococcus and Escherichia genus. The worst results have been observed against all strains of Pseudomonas aeruginosa. PMID- 22313308 TI - Antimicrobial activity and SAR study of some novel thiosemicarbazide derivatives bearing piperidine moiety. AB - In this study novel thiosemicarbazides bearing piperidine moiety were synthesized in order to investigate their possible antibacterial and antifungal activities. A structure-activity relationship (SAR) study including conformational analysis and some physicochemical descriptors was carried out to provide the guidance for further synthetic work. The significant molecular descriptors related to the compounds with antifungal activity were: electrostatic potential surface, the highest occupied molecular orbital energy, surface area, volume, and hydration energy. PMID- 22313309 TI - Synthesis, structure and antibacterial evaluation of some N-substituted 3-amino-5 hydroxy-4-phenyl-1H-pyrazole-1-carboxamides. AB - N-substituted 3-amino-5-hydroxy-4-phenyl-1H-pyrazole-1-carboxamide derivatives have been prepared by heterocyclization of 1-cyanophenyl acetic acid hydrazide with isocyanates. Representative compounds were evaluated as potential antimicrobial agents. The most promising compound in this series, the N-(1 naphthyl)-3-amino-5-hydroxy-4-phenyl-1H-pyrazole-1-carboxamide 2f, was the most effective against the reference strains of pathogenic S. aureus ATCC 25923 and S. aureus ATCC 6538 or opportunistic S. epidermidis ATCC 12228 with MIC value of 7.81 MUg/ml and against the other gram-positive species with MIC values 15.63 31.25 MUg/ml. This compound also showed high activity against clinical isolates of MSSA (methicillin-sensitive Staphylococcus aureus) with MIC of 0.98-31.25 MUg/ml and MRSA (methicillin-resistant Staphylococcus aureus) with MIC of 1.96 7.81 MUg/ml. PMID- 22313310 TI - Synthesis and in vitro leishmanicidal activity of disulfide derivatives. AB - Disulfides 1-30 have been synthesized and their in vitro leishmanicidal activity has been evaluated. Compounds 18 (IC50 = 2.70 +/- 0.044 MUM), 19 (IC50 = 2.85 +/- 0.02 MUM), 20 (IC50 = 2.92 +/- 0.01 MUM), 26 (IC50 = 3.69 +/- 0.01 MUM), 21 (IC50 = 4.45 +/- 0.029 MUM), and 29 (IC50 = 4.46 +/- 0.025 MUM) showed a remarkable leishmanicidal activity if compared with standard pentamidine (IC50 = 5.09 +/- 0.04 MUM). This study has discovered a series of possible molecules as antileishmanial agents. A structure-activity relationship study has also been carried out. The structures of all the synthesized compounds were identified by using spectroscopic techniques, including 1H-NMR and EI MS. PMID- 22313311 TI - Novel hexahydropyridoindole derivative as prospective agent against oxidative damage in pancreatic beta cells. AB - The potential protective effect of (+/-)-8-methoxy-1,3,4,4a,5,9b-hexahydro pyrido[4,3-b]indole-2-carboxylic acid ethyl ester (II) was assessed against hydrogen peroxide (H2O2)-cytotoxicity in rat pancreatic INS-1E beta cells and compared with the effect of the related pyridoindole, stobadine (I), a promising indole-type reference antioxidant. Only pre-treatment with the compound (II) led to a significant preservation of the metabolic and secretory functions of the cells exposed to H2O2. The caspase-9 and -3 activities, as well as the early apoptotic changes of plasma membrane, were suppressed in the cells pre-incubated with both of compounds tested. However, only pyridoindole (II) inhibited profoundly the time-delayed apoptotic changes, These results suggest that pyridoindole (II) characterized by enhanced intrinsic antioxidant efficiency, may protect beta cells against cytotoxic effects of H2O2, involved in the development of both type 1 and type 2 diabetes. PMID- 22313312 TI - Cloning, expression and characterization of mouse (Mus musculus) nicotinamide 5' mononucleotide adenylyltransferase-2. AB - Nicotinamide adenine dinucleotide (NAD+) is synthesized by the action of nicotinamide mononucleotide adenylyltransferase (NMNAT) from NMN and ATP. The mouse homolog of NMNAT-2 (mmNMNAT-2) was cloned, expressed, and subsequently identified using MALDI-TOF in conjunction with the ProFound database. Circular dichroism analyses of recombinant mmNMNAT-2 showed alpha helical and beta sheet secondary structures, consistent with the known structure of the human isoform. Competition experiments using mouse pancreatic tissue lysates with recombinant mmNMNAT-2 demonstrated that the activity of the expressed protein was similar to the human isoform. Immunohistochemistry of mouse embryonic tissues with hNMNAT-2 also showed a tissue- and cellular-specific expression of this isoform. Therefore, our studies demonstrate for the first time the clear biological evidence for the existence of a mouse isoform of hNMNAT-2. These studies may help in future investigations aimed at understanding the regulation of this gene and its pathway, and in turn, will spur the development of novel therapies for diseases such as cancer and diabetes since mice are the most frequently used experimental system for in vivo studies. PMID- 22313313 TI - Synthesis and evaluation of biological activities of a series of (6-substituted benzothiazol-2-yl)acrylamides. AB - A series of simple (6-substituted benzothiazol-2-yl)acrylamides was synthesized and evaluated for cytotoxicity and antimicrobial effects. All six compounds displayed very significant cytotoxicity against four cancer cell lines tested including A549 (a human lung cancer cell line), Hela (a human ovarian cancer cell line), MCF7 (a human breast cancer cell line), and even MCF7-ADR (adriamycin resistant human breast cancer cell line), with IC(50) values in microgram/ml range and as low as 0.66 MUg/ml. The synthesized compounds also exhibited some antifungal effects against Apergillus niger. PMID- 22313314 TI - Comparison between atrial fibrillation-triggered implantable cardioverter defibrillator (ICD) shocks and inappropriate shocks caused by lead failure: different impact on prognosis in clinical practice. AB - INTRODUCTION: Recent studies suggest a worse impact of inappropriate shock therapies on the outcome of patients with an implantable cardioverter defibrillator (ICD). However, it is not known whether the worse impact is attributed to the ICD shock itself or due to the underlying heart disease. The aim of the study was to evaluate the impact of inappropriate ICD shocks on clinical outcome by comparing ICD shocks triggered by atrial fibrillation (AF) with shocks caused by lead failure. METHODS AND RESULTS: A total of 1,411 consecutive patients of the prospective single-center ICD-registry Ludwigshafen who underwent an ICD implantation between 1992 and 2008 for primary or secondary prevention of sudden cardiac death were analyzed. During the median follow-up of 3 years, 297 (21%) patients experienced inappropriate ICD shocks. Sixty percent of patients had inappropriate shocks due to AF and 24% due to lead defect or T wave oversensing. Multiple ICD shocks (>=2) triggered by AF were associated with a worse prognosis, whereas a single shock due to AF or 1 or multiple shocks resulting from lead failure were not. ICD shocks caused by AF occurred more often in tandem with a serious adverse event than in patients with a lead failure (15% vs 6%, P < 0.05). CONCLUSION: Multiple ICD shocks triggered by AF are associated with a worse prognosis in ICD patients, whereas a single shock due to AF or shocks resulting from lead failure are not. These data support that the ICD shock itself has no worse impact on the outcome of ICD patients. PMID- 22313315 TI - Phosphine coordination to a cobalt diimine-dioxime catalyst increases stability during light-driven H2 production. AB - The combination of cobalt diimine-dioxime complexes with a cyclometalated iridium photosensitizer gives efficient systems for hydrogen generation under visible light irradiation using triethylamine as a sacrificial electron donor. Interestingly, the addition of triphenylphosphine (PPh(3)) to the medium results in a significant improvement of the stability of the system, with up to ~700 turnovers achieved within 10 h. UV-visible spectroscopic monitoring of the reaction allows identification of a PPh(3)-coordinated Co(I) intermediate as the active species. Mechanistic issues regarding (i) the photogeneration of the Co(I) species, (ii) the nature of the active species, and (iii) the influence of PPh(3) on the H(2)-evolution mechanism are discussed. PMID- 22313316 TI - Long-term oestradiol treatment enhances hippocampal synaptic plasticity that is dependent on muscarinic acetylcholine receptors in ovariectomised female rats. AB - Short-term oestradiol treatment modulates hippocampus-dependent memory and synaptic plasticity in the hippocampus. Long-term oestradiol treatment can also enhance hippocampus- dependent memory, although the effects of long-term oestradiol treatment on synaptic plasticity are unknown. We investigated the effects of long-term oestradiol treatment on synaptic plasticity at the Schaeffer Collateral/CA1 synapse in 8-month-old female rats. In addition, we determined the role of endogenous activation of muscarinic acetylcholine receptors (mAChRs) in synaptic transmission and plasticity using scopolamine (1 MUm), an antagonist of mAChRs. Hippocampus slices from ovariectomised rats that were treated with oestradiol-containing capsules for 5 months were compared with slices from ovariectomised rats that received cholesterol-containing capsules. Unexpectedly, scopolamine application significantly increased the baseline field excitatory postsynaptic potentials (fEPSP) and decreased paired pulse facilitation (PPF) in slices from cholesterol-treated rats. Baseline fEPSPs and PPF were not significantly modulated in slices from oestradiol-treated rats by scopolamine. Slices from oestradiol-treated rats showed enhanced long-term potentiation relative to slices from cholesterol-treated rats. Scopolamine significantly reduced the magnitude of plasticity in slices from oestradiol-treated rats. Taken together, these results suggest that mAChRs have a significant effect on baseline synaptic transmission through a decrease in the probability of glutamate release in slices from cholesterol-treated rats. Long-term oestradiol treatment blocks this effect and enhances theta-burst stimulation-induced synaptic plasticity in the middle-aged female rat, and this effect is mediated by activation of mAChRs. PMID- 22313317 TI - Importance of hemoglobin concentration and its modification for the outcome of head and neck cancer patients treated with radiotherapy. AB - INTRODUCTION: Hypoxia induced radioresistance has been acknowledged for decades. One of the indirect evidences of the influence of hypoxia on radiation response comes from the observations of a correlation between tumor control and hemoglobin level. This review examines the clinical data on the prognostic and predictive role of hemoglobin level and hemoglobin manipulation in radiotherapy of squamous cell carcinomas of the head and neck, a tumor type where hypoxic radioresistance have been previously documented. THE INFLUENCE OF HEMOGLOBIN CONCENTRATION ON TUMOR OXYGENATION AND OUTCOME: The aim is to evaluate the existing literature for information of the influence of hemoglobin concentration and hemoglobin modifications on tumor oxygenation and outcome in head and neck squamous cell cancer patients. The data from several randomized trials show that while most studies have confirmed the prognostic value of hemoglobin, increasing the hemoglobin level through transfusion or erythropoietin stimulation did not result in improved outcome for patients with low initial hemoglobin levels. Clinical studies showed that smoking reduced the oxygen carrying capacity of the blood through formation of carboxyhemoglobin, and lead to poorer response to radiotherapy in smokers compared to non-smokers. Smoking also increased the risk of the development of secondary cancers. CONCLUSION AND FUTURE PERSPECTIVES: In conclusion, low hemoglobin is a significant negative prognostic factor for radiotherapy of head and neck cancer. Correction of pre-treatment low hemoglobin by blood transfusion and/or erythropoietin stimulating agents does, however, not improve the outcome. Smoking leads to a decrease in effective hemoglobin and poorer treatment outcome. Smoking should be avoided in order to improve the therapeutic efficacy of radiotherapy and development of other smoking-related diseases and/or secondary cancers. PMID- 22313318 TI - A rationale of ginseng as a novel addition to the antihirsutism armamentarium. PMID- 22313319 TI - The initial cancer pathway for children - one-fourth wait more than 3 months. AB - AIM: To determine the time intervals from symptom to treatment for childhood cancer patients. METHODS: Danish national population-based study. Children (<15 years) with an incident cancer diagnosed from January 2007 to December 2010 were sampled. A total of 376 (68%) parents and 315 (87%) general practitioners (GPs) completed questionnaires on the diagnostic pathway. The time interval was categorized into, patient-, GP-, system-, diagnostic- and total intervals, and as short or long intervals. Factors associated with long time intervals were assessed in a logistic regression model using prevalence ratios (PRs). RESULTS: Girls were almost twice as likely as boys to experience long patient intervals (adjusted PR: 1.8, 95% confidence interval (CI): 1.1-2.8). The oldest children were more likely than the youngest to experience long total intervals (adjusted PR: 1.9, 95% CI: 1.1-3.3). Cancer type was associated with all time intervals, except GP intervals. Children with bone- and CNS tumours had the longest total intervals (median: 88 days, interquartile interval (IQI): 57-132) vs. (median: 76, IQI: 28-191). Parental education showed a possible association with patient- and GP intervals. CONCLUSION: Time intervals varied by gender, age and cancer type. Parental education may possibly affect the patient- and GP intervals. PMID- 22313320 TI - Tracking of single charge carriers in a conjugated polymer nanoparticle. AB - The motion of individual charge carriers in organic nanostructures was tracked by fluorescence microscopy. A twinkling effect is observed in fluorescence microscopy of single conjugated polymer nanoparticles, that is, small displacements in the fluorescence spot of single nanoparticles of the conjugated polymer PFBT are observed over time. There is evidence that superquenching by the charge carrier induces a dark spot in the nanoparticle, which moves with the carrier, resulting in the observed displacements in the fluorescence. Zero-field mobilities of individual charge carriers consistent with highly trapped polarons were obtained from tracking experiments. PMID- 22313321 TI - Guidelines on the investigation and management of antiphospholipid syndrome. PMID- 22313322 TI - Review article: the natural history of postoperative Crohn's disease recurrence. AB - BACKGROUND: Surgical resection of the diseased bowel in Crohn's disease is unfortunately not curative, and postoperative recurrence remains a problem in these patients. AIM: To review the rates of and risk factors for clinical and endoscopic recurrence in population-based studies, referral centres and randomised controlled trials. METHODS: We searched MEDLINE (source PUBMED, 1966 to September, 2011). RESULTS: In randomised controlled trials, clinical recurrence in the first year after surgery occurred in 10-38% of patients, whereas endoscopic recurrence in the first year was reported in 35-85% of patients. In population-based studies, approximately half of patients experienced clinical recurrence at 10 years. In referral centres, 48-93% of the patients had endoscopic lesions (Rutgeerts' score >=1) in the neoterminal ileum within 1 year after surgery, whereas 20-37% had symptoms suggestive of clinical recurrence. Three years after surgery, the endoscopic postoperative recurrence rate increased to 85-100%, and symptomatic recurrence occurred in 34-86% of patients. Smoking is the strongest risk factor for postoperative recurrence, increasing by twofold, the risk of clinical recurrence. Prior intestinal resection, penetrating behaviour, perianal disease and extensive bowel disease (>50 cm) are established risk factors for postoperative recurrence. Risk factors for postoperative recurrence remain poorly defined in population-based cohorts. CONCLUSION: Endoscopic and clinical postoperative recurrence remains common in patients with Crohn's disease, and the identification of risk factors may allow targeted strategies to reduce this recurrence rate. PMID- 22313323 TI - Regulation of SFRP-1 expression in the rat dental follicle. AB - Tooth eruption requires osteoclastogenesis and subsequent bone resorption. Secreted frizzled-related protein-1 (SFRP-1) negatively regulates osteoclastogenesis. Our previous studies indicated that SFRP-1 is expressed in the rat dental follicle (DF), with reduced expression at days 3 and 9 close to the times for the major and minor bursts of osteoclastogenesis, respectively; but it remains unclear as to what molecules contribute to its reduced expression at these critical times. Thus, it was the aim of this study to determine which molecules regulate the expression of SFRP-1 in the DF. To that end, the DF cells were treated with cytokines that are maximally expressed at days 3 or 9, and SFRP 1 expression was determined. Our study indicated that colony-stimulating factor-1 (CSF-1), a molecule maximally expressed in the DF at day 3, down-regulated SFRP-1 expression. As to endothelial monocyte-activating polypeptide II (EMAP-II), a highly expressed molecule in the DF at day 3, it had no effect on the expression of SFRP-1. However, when EMAP-II was knocked down by siRNA, the expression of SFRP-1 was elevated, and this elevated SFRP-1 expression could be reduced by adding recombinant EMAP-II protein. This suggests that EMAP-II maintained a lower level of SFRP-1 in the DF. TNF-alpha is a molecule maximally expressed at day 9, and this study indicated that it also down-regulated the expression of SFRP-1 in the DF cells. In conclusion, CSF-1 and EMAP-II may contribute to the reduced SFRP 1 expression seen on day 3, while TNF-alpha may contribute to the reduced SFRP-1 expression at day 9. PMID- 22313324 TI - Mechanistic studies on direct arylation of pyridine N-oxide: evidence for cooperative catalysis between two distinct palladium centers. AB - Direct arylations of pyridine N-oxide (PyO), a convenient method to prepare 2 arylpyridines, catalyzed by Pd(OAc)(2) and PtBu(3) have been proposed to occur by the generation of a PtBu(3)-ligated arylpalladium acetate complex, (PtBu(3))Pd(Ar)(OAc) (1), and the reaction of this complex with PyO. We provide strong evidence that 1 does not react directly with PyO. Instead, our data imply that the cyclometalated complex [Pd(OAc)(tBu(2)PCMe(2)CH(2))](2), which is generated from the decomposition of 1, reacts with PyO and serves as a catalyst for the reaction of PyO with 1. The reaction of PyO with 1 occurs with an induction period, and the reaction of 1 with excess PyO in the presence of [Pd(OAc)(tBu(2)PCMe(2)CH(2))](2) is zeroth-order in 1. Moreover, the rates of reactions of PyO with bromobenzene catalyzed by [Pd(OAc)(tBu(2)PCMe(2)CH(2))](2) and [Pd(PtBu(3))(2)] depend on the concentration of [Pd(OAc)(tBu(2)PCMe(2)CH(2))](2) but not on the concentration of [Pd(PtBu(3))(2)]. Finally, the reaction of 1 with a model heteroarylpalladium complex containing a cyclometalated phosphine, [(PEt(3))Pd(2 benzothienyl)(tBu(2)PCMe(2)CH(2))], rapidly formed the arylated heterocycle. Together, these data imply that the rate-determining C-H bond cleavage occurs between PyO and the cyclometalated [Pd(OAc)(tBu(2)PCMe(2)CH(2))](2) rather than between PyO and 1. In this case, the resulting heteroarylpalladium complex transfers the heteroaryl group to 1, and C-C bond-formation occurs from (PtBu(3))Pd(Ar)(2-pyridyl oxide). This mechanism proposed for the direct arylation of PyO constitutes an example of C-H bond functionalization in which C H activation occurs at one metal center and the activated moiety undergoes functionalization after transfer to a second metal center. PMID- 22313325 TI - Cytoplasmic estrogen receptor beta as a potential marker in human non-small cell lung carcinoma. AB - OBJECTIVES: Estrogen has been reported to promote an increased susceptibility to lung cancer development. This study focusses on the role of cytoplasmic estrogen receptor beta (c-ERbeta) in NSCLC. METHODS: NSCLC (n = 162) cases were analyzed using immunohistochemistry (IHC) for c-ERbeta expression and its association with clinicopathological variables. Significance of c-ERbeta expression was further examined using in vitro studies in NSCLC cell lines. RESULTS: Among ERbeta and aromatase positive NSCLC females, c-ERbeta was significantly associated with greater tumor diameter and tended to be associated with worse overall survival. A549 and LCAM1 cells expressed aromatase, as well as c-ERbeta and nuclear ERbeta (n-ERbeta). U0126 (MAPK/extracellular-signal-regulated kinase (ERK) inhibitor) abrogated MAPK phosphorylation, caused by estradiol via c-ERbeta, more effectively than ICI 182780 (ER blocker) in either cell line. However, ICI 182780 completely abrogated the estrogen responsive elements (ERE)-luciferase activity caused by estradiol. Combination therapy with ICI 182780 and U0126 turned out to be far more effective than either treatment alone in either A549 or LCAM1 cells. CONCLUSION: The results indicated that ERbeta may contribute to NSCLC via non genomic action of estrogen through its cytoplasmic form, in addition to the genomic actions via n-ERbeta. These actions of estrogen in NSCLCs may be abrogated by combination therapy with ICI 182780 and U0126. PMID- 22313326 TI - Economic evaluation of tocilizumab combination in the treatment of moderate-to severe rheumatoid arthritis in Italy. AB - OBJECTIVE: This study was designed to evaluate the cost utility of tocilizumab in rheumatoid arthritis (RA) patients, with inadequate responses to traditional disease-modifying anti-rheumatic drugs (tDMARDs) from a payer's perspective in Italy. METHODS: An individual patient simulation model was used to project lifetime medical costs (payer's perspective) and quality-adjusted life-years (QALYs). Treatment sequences starting with tocilizumab or the most commonly prescribed biologics (etanercept, adalimumab, or infliximab) were compared. The addition of tocilizumab to standard of care, without the replacement of anti tumor necrosis factor (TNF)-alpha treatments, was also evaluated. Patient characteristics, treatment efficacy, and quality-of-life data were based on three phase 3 tocilizumab clinical trials (TOcilizumab Pivotal Trial in Methotrexate Inadequate respONders [OPTION], Tocilizumab in cOmbination With traditional DMARD therapy [TOWARD], and TociLIzumab Safety and THE Prevention of Structural Joint Damage [LITHE]). Mixed-treatment comparison was used to estimate response probabilities. Resource utilization, treatment acquisition, administration, and monitoring costs were estimated using Italian secondary sources. Uncertainty in model parameters was evaluated by probabilistic sensitivity analysis. RESULTS: Replacement of anti-TNF-alpha treatments with tocilizumab reduced total costs over a patient's lifetime (base-case analysis: tocilizumab sequence, ?141,100 vs standard of care sequence, ?143,500). Patients receiving tocilizumab realized more QALYs than patients receiving standard of care (9.8881 vs 9.3502 QALYs). Therefore, according to the base-case analysis, the tocilizumab sequence dominated the standard of care. In a sensitivity analysis, the model base-case result was robust to input changes. When tocilizumab was added to standard of care, without replacing anti-TNF-alpha treatments, the incremental cost effectiveness ratio was ?17,100 per QALY. CONCLUSION: The analysis demonstrates that, in Italy, replacing another biologic DMARD with tocilizumab or adding tocilizumab to the current standard of care is a cost-effective strategy in the treatment of RA patients with inadequate responses to tDMARDs. PMID- 22313327 TI - Development and psychometric validation of the Diabetes Therapy-Related QOL (DTR QOL) questionnaire. AB - OBJECTIVE: We developed and evaluated the psychometric properties of the Diabetes Therapy-Related QOL (DTR-QOL) as a disease-specific, self-administered questionnaire to assess the influence of diabetes treatment on patient QOL, regardless of treatment method. METHODS: This new questionnaire was developed and validated in a standardized manner: Item development, pilot-testing and psychometric validation. A survey was conducted using the provisional version of the questionnaire, and reliability and validity were evaluated with psychometric testing. RESULTS: The provisional version of the questionnaire was generated with 29 items through literature review and pilot testing. For psychometric assessment, analyses were performed on the responses of 284 adult Japanese patients with diabetes. Factor analysis by the principal factor method with promax rotation revealed 4 factors; "burden on social activities and daily activities" (13 items), "anxiety and dissatisfaction with treatment" (8 items), "hypoglycemia" (4 items), and "satisfaction with treatment" (4 items). For reliability, the intraclass correlation was 0.92, and Cronbach's alpha coefficient was 0.94, indicating adequate test-retest reliability and internal consistency. For known-group validity, there were significant differences in scores for following variables: age, diabetes type, HbA1c, treatment method, glycemic control, hypoglycemia, nocturnal hypoglycemia, concern about weight gain, health status (patient assessment), and degree of communication with physician. CONCLUSIONS: The DTR-QOL, with good reliability and validity, can assess the influence of diabetes treatment on patient QOL. The DTR-QOL can be used regardless of treatment method that patients receive, and this characteristic enables to detect a difference on patients QOL between treatment methods before and after a switch of treatment. Limitations of this study include representativeness of the patient sample. The relatively small number of patients with type 1 diabetes should be noted. Also, responsiveness of the DTR-QOL has not yet been examined. PMID- 22313328 TI - Cost-effectiveness of cinacalcet in secondary hyperparathyroidism in the United States. AB - OBJECTIVE: Cinacalcet has been used in controlling secondary hyperparathyroidism (SHPT) in dialysis patients since 2004, but its full economic evaluation has not been conducted from the US perspective. This study assesses the cost effectiveness of cinacalcet and low-dose vitamin D for the treatment of SHPT in dialysis patients compared with flexible vitamin D. METHODS: A lifetime patient level simulation model was developed using ADVANCE trial data, including biomarker levels: parathyroid hormone, calcium, and phosphorus. The impact of the biomarkers on mortality, cardiovascular events, fractures, and parathyroidectomy were estimated from literature: Block, an observational study; Cunningham, a combined analysis of four randomized trials of cinacalcet; and Danese, a study investigating the effect of duration in recommended targets. Baseline event rates were derived from the large dialysis organizations registries. One-way and probabilistic sensitivity analyses (PSA) were conducted. RESULTS: The cost effectiveness ratio for cinacalcet compared with standard of care (vitamin D and phosphate binders) was $54,560 and $72,456/quality-adjusted-life-year (QALY) gained or an incremental cost of $3155 and $2638 per year alive for the Block and Danese variants, respectively. In the Cunningham variant, cost-effectiveness ratio for cinacalcet was $5064/QALY gained or a cost saving of $1068 per year. The difference in the results of the Cunningham variant vs other variants can be explained by the favorable impact of cinacalcet on outcomes, specifically cardiovascular events observed in the Cunningham study. The PSA showed 98% likelihood for cinacalcet to be cost-effective at $100,000/QALY threshold. LIMITATIONS: Observational data assessing effects on clinical outcomes, trial restriction to use calcium-containing phosphate binders, no utility data in SHPT dialysis population, and insufficient evidence on long-term impact of cinacalcet and vitamin D on biochemical markers. CONCLUSIONS: Cinacalcet treatment is cost effective for treatment of SHPT in the US. Due to cost offsets, cinacalcet can reduce annual costs in some scenarios. PMID- 22313329 TI - Quality of life benefits and cost impact of prolonged release oxycodone/naloxone versus prolonged release oxycodone in patients with moderate-to-severe non malignant pain and opioid-induced constipation: a UK cost-utility analysis. AB - OBJECTIVE: To compare the cost effectiveness of prolonged release oxycodone/naloxone (OXN) tablets (Targinact) and prolonged release oxycodone (OXY) tablets (OxyContin) in patients with moderate-to-severe non-malignant pain and opioid-induced constipation (OIC) from the perspective of the UK healthcare system. METHODS: A cohort model used data from a phase III randomised, controlled trial (RCT). It calculated the cost difference between treatments by combining the cost of pain therapy with costs of laxatives and other resources used to manage constipated patients. SF-36 scores were converted into EQ-5D utility values to calculate the quality-adjusted life-year (QALY) gains. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: The incremental cost of OXN versus OXY was L159.68 for the average treatment duration of 301 days. OXN gave an incremental QALY gain of 0.0273. The estimated incremental cost effectiveness ratio (ICER) was L5841.56 per QALY. Sensitivity analyses gave a maximum ICER of L10,347.03. In some scenarios, OXN dominated with a cost saving of up to L4254.70. Probabilistic sensitivity analysis showed that OXN had approximately 96.6% probability of cost effectiveness at the L20,000 threshold. LIMITATIONS: The model was conservative in predicting the probability of constipation beyond the 12-week RCT period. UK cost of constipation data were limited and based on primary care physician opinion. CONCLUSIONS: In the base case, direct treatment costs were slightly higher for patients treated with OXN than for those treated with OXY. However, patients treated with OXN experienced a quality of life gain, and had an ICER considerably below thresholds commonly applied in the UK. The model was most sensitive to the estimated cost of constipation with a number of realistic scenarios in the sensitivity analysis demonstrating a cost saving with OXN (OXN dominant). OXN is therefore estimated to be a cost-effective option for treating patients with severe non-malignant pain and OIC. PMID- 22313330 TI - The cost to managed care of managing pulmonary hypertension. AB - OBJECTIVE: To estimate direct medical costs and resource use for commercially insured patients within two pulmonary hypertension sub-groups: pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). RESEARCH DESIGN AND METHODS: Using a retrospective cohort design, subjects (>=18 years) with ICD-9 code 416.0 (PAH or CTEPH) or 416.8 (CTEPH) were identified during 2004-2009 within the MarketScan database. The date of the first observed claim was the index date. Each PAH and CTEPH patient was matched to one-to-five controls without PAH and CTEPH on age, gender, region, and payer type. Patients and controls were continuously enrolled for at least 12 months pre- and 12 months post-index date. Per-patient-per-month costs and resource use were compared using Wilcoxon rank-sum test. RESULTS: PAH patients (1647) and controls (6352) were identified (mean age 63 years, 73% female). Total monthly costs before PAH diagnosis were: PAH patients $2064 vs controls $1094. After PAH diagnosis, PAH patients had significantly higher monthly costs and resource use vs controls: Total costs $4021 vs $1533, outpatient visits 1.1 vs 0.8, inpatient visits 0.7 vs 0.2, prescriptions 3.6 vs 2.7, all p-values <0.05. One hundred and forty-six CTEPH patients and 558 controls were identified (mean age 64 years, 54.8% female). Total monthly costs in the period before CTEPH diagnosis were higher for CTEPH patients ($3895) than controls ($1177). After CTEPH diagnosis, CTEPH patients had significantly higher monthly costs and resource use vs controls: Total costs $6198 vs $1579, Outpatient visits 1.2 vs 0.8, inpatient visits 2 vs 0.2, prescriptions 4.2 vs 2.8, all p-values <0.05. KEY LIMITATIONS: Identification of PAH is complicated, as there exists no precise ICD-9-CM code for the condition. CTEPH diagnosis was based upon claims data and was not verified clinically. CONCLUSIONS: CTEPH and PAH patients incurred higher costs and used more resources than controls in the baseline and follow-up periods. PMID- 22313332 TI - An earnest search for atrial fibrillation patients without thromboembolic risk. PMID- 22313333 TI - Ageing: a risk factor for amyloid A amyloidosis in rheumatoid arthritis. PMID- 22313331 TI - Roles of white matter in central nervous system pathophysiologies. AB - The phylogenetic enlargement of cerebral cortex culminating in the human brain imposed greater communication needs that have been met by the massive expansion of WM (white matter). Damage to WM alters brain function, and numerous neurological diseases feature WM involvement. In the current review, we discuss the major features of WM, the contributions of WM compromise to brain pathophysiology, and some of the mechanisms mediating WM injury. We will emphasize the newly appreciated importance of neurotransmitter signalling in WM, particularly glutamate and ATP signalling, to understanding both normal and abnormal brain functions. A deeper understanding of the mechanisms leading to WM damage will generate much-needed insights for developing therapies for acute and chronic diseases with WM involvement. PMID- 22313334 TI - Equilibrium and NMR relaxometric studies on the s-triazine-based heptadentate ligand PTDITA showing high selectivity for Gd3+ ions. AB - A complete potentiometric and NMR relaxometric solution study on the heptadentate 2,2',2",2'"-[(6-piperidinyl-1,3,5-triazine-2,4-diyl)dihydrazin-2-yl-1 ylidene]tetraacetic acid (PTDITA) ligand has been carried out. This ligand is based on the 1,3,5-triazine ring with two hydrazine-N,N-diacetate groups in positions 2 and 4 and a piperidine moiety in position 6. The introduction of the triazine ring into the ligand backbone is expected to modify its flexibility and then to affect the stability of the corresponding complexes with transition-metal and lanthanide ions. Thermodynamic stabilities have been determined by pH potentiometry, UV spectrophotometry, and (1)H NMR spectroscopy for formation of the complexes with Mg(2+), Ca(2+), Cu(2+), Zn(2+), La(3+), Gd(3+), and Lu(3+) ions. PTDITA shows a good binding affinity for Gd(3+) (logK = 18.49, pGd = 18.6) and an optimal selectivity for Gd(3+) over the endogenous Ca(2+), Zn(2+), and Cu(2+) (K(sel) = 6.78 * 10(7)), which is 3 orders of magnitude higher that that reported for Gd(DTPA) (K(sel) = 2.85 * 10(4)). This is mainly due to the lower stability of the Cu(II)- and Zn(II)(PTDITA) complexes compared to the corresponding DTPA complexes, which suggests an important role of the triazine ring on the selectivity for the Gd(3+) ion. The relaxometric properties of Gd(PTDITA) have been investigated in aqueous solution by measuring the (1)H relaxivity as a function of the pH, temperature, and magnetic field strength (nuclear magnetic relaxation dispersion profile). Variable-temperature (17)O NMR data have provided direct information on the kinetic parameters for exchange of the coordinated water molecules. A simultaneous fit of the data suggests that the high relaxivity value (r(1) = 10.2 mM(-1) s(-1)) is a result of the presence of two inner-sphere water molecules along with the occurrence of relatively slow rotation and electronic relaxation. The water residence lifetime, (298)tau(M) = 299 ns, is quite comparable to that of clinically approved magnetic resonance imaging contrast agents. The displacement of the inner-sphere water molecules by bidentate endogeneous anions (citrate, phosphate, and carbonate) has also been evaluated by (1)H relaxometry. In general, the binding interaction is markedly weak, and only in the case of citrate, a ca. 35% decrease in relaxivity was observed in the presence of 60 equiv of the anion. Phosphate and carbonate also interact with the paramagnetic ion, likely as monodentate ligands, but formation of the ternary complex is accompanied by a modest increase of r(1) due to the contribution of second-sphere water molecules. PMID- 22313335 TI - Luminal decoration of blood vessels by activated perivasal mast cells in allergic rhinitis. AB - BACKGROUND: In allergic diseases, like in rhinitis, antigen challenge induces rapid degranulation of tissue resident mast cells and subsequent recruitment of leukocytes in response to soluble immunmodulators. The fate of mast cell-derived, membrane associated factors in inflamed tissue remained however unresolved. METHODS: Components of the mast cell granular membrane, including the unique marker CD63var, were examined by FACS and by confocal laser scanning microscopy in cell culture and in diseased human tissue. RESULTS: We discovered that selected mast cell membrane components appeared on the surface of distinct bystander cells. Acceptor cells did not acquire these molecules simply by uptake of soluble material or in the form of exosomes. Instead, physically stable cell to-cell contact was required for transfer, in which a Notch2-Jagged1 interaction played a decisive role. This process is activation-dependent, unidirectional, and involves a unique membrane topology. Endothelial cells were particularly efficient acceptors. In organotypic 3D in vitro cultures we found that transferred mast cell molecules traversed an endothelial monolayer, and reappeared focally compacted on its distal surface, away from the actual contact zone. Moreover, we observed that such mast cell-derived membrane patches decorate microcapillaries in the nasal mucosa of allergic rhinitis patients. CONCLUSION: Direct membrane transfer from perivasal mast cells into nearby blood vessels constitutes a novel mechanism to modulate endothelial surface features with apparent significance in allergic diseases. PMID- 22313336 TI - The validity of biochemical markers in metabolic bone disease in preterm infants: a systematic review. AB - To establish the validity of biochemical markers of metabolic bone disease (MBD) in preterm infants. CONCLUSION: There is insufficient evidence that any of the frequently used serum measurements are valid biochemical markers of MBD in preterm infants. Increased urinary calcium concentration may be a valid biochemical marker, but more research is necessary to confirm this. PMID- 22313337 TI - In vitro fermentation of a red wine extract by human gut microbiota: changes in microbial groups and formation of phenolic metabolites. AB - An in vitro batch culture fermentation experiment was conducted with fecal inocula from three healthy volunteers in the presence and absence of a red wine extract. Changes in main bacterial groups were determined by FISH during a 48 h fermentation period. The catabolism of main flavonoids (i.e., flavan-3-ols and anthocyanins) and the formation of a wide a range of phenolic microbial metabolites were determined by a targeted UPLC-PAD-ESI-TQ MS method. Statistical analysis revealed that catechol/pyrocatechol, as well as 4-hydroxy-5-(phenyl) valeric, 3- and 4-hydroxyphenylacetic, phenylacetic, phenylpropionic, and benzoic acids, showed the greatest increases in concentration during fermentation, whereas 5-(3'-hydroxyphenyl)-gamma-valerolactone, its open form 4-hydroxy-5-(3' hydroxyphenyl)-valeric acid, and 3,4-dihydroxyphenylacetic acid represented the largest interindividual variations in the catabolism of red wine polyphenols. Despite these changes, microbial catabolism did not produce significant changes in the main bacterial groups detected, although a slight inhibition of the Clostridium histolyticum group was observed. PMID- 22313339 TI - Transmembrane potential across single conical nanopores and resulting memristive and memcapacitive ion transport. AB - Memristive and memcapacitive behaviors are observed from ion transport through single conical nanopores in SiO(2) substrate. In i-V measurements, current is found to depend on not just the applied bias potential but also previous conditions in the transport-limiting region inside the nanopore (history dependent, or memory effect). At different scan rates, a constant cross-point potential separates normal and negative hysteresis loops at low and high conductivity states, respectively. Memory effects are attributed to the finite mobility of ions as they redistribute within the negatively charged nanopore under applied potentials. A quantative correlation between the cross-point potential and electrolyte concentration is established. PMID- 22313338 TI - Survival for ovarian cancer in Europe: the across-country variation did not shrink in the past decade. AB - BACKGROUND: Survival for ovarian cancer is the poorest of all gynaecological cancer sites. Our aim was to present the most up-to-date survival estimate for ovarian cancer by age and morphology and to answer the question whether survival for ovarian cancer improved in Europe during the 1990s. MATERIAL AND METHODS: This analysis was performed with data from the EUROCARE database. We considered all adult women diagnosed with ovarian cancer between 1995 and 2002 and life status followed up until the end of 2003. A total of 97 691 cases were contributed by 72 European cancer registries in 24 countries. We estimated the most up-to-date relative survival for a mean of 23 661 patients followed up in 2000-2003 using the period hybrid approach and described the relative survival trends from the beginning of 1990s. RESULTS AND CONCLUSION: Overall, the European age-standardised one-year, five-year and five-year conditional on surviving one year relative survival were 67.2% (95% CI 66.6-67.8), 36.1% (95% CI 35.4-36.8) and 53.7% (95% CI 52.8-54.7), respectively. Five-year relative survival was 58.6% (95% CI 57.4-59.8), 37.1% (95% CI 36.1-38.1) and 20.5% (95% CI 19.1-21.9) in women aged 15-54, 55-74 and 75-99 years, respectively. The age-standardised five year relative survival was 38.1% (95% CI 36.9-39.3) for serous tumours and 51.9% (95% CI 49.0-54.9) for mucinous cancers and the crude five-year relative survival was 85.6% (95% CI 81.2-90.0) for germ cell cancers. Overall, the age-standardised five-year relative survival increased from 32.4% (95% CI 31.7-33.2) in 1991-1993 to 36.3% (95% CI 35.5-37.0) in 2000-2003. There is a need to better understand the reasons for the wide variation in survival of ovarian cancer in Europe. Actions aiming to harmonise the protocols for therapy should contribute to narrowing the wide gap in survival and research on screening and early detection of ovarian cancer should be enforced. PMID- 22313341 TI - Radial sizing of lipid nanotubes using membrane displacement analysis. AB - We report a novel method for the measurement of lipid nanotube radii. Membrane translocation is monitored between two nanotube-connected vesicles, during the expansion of a receiving vesicle, by observing a photobleached region of the nanotube. We elucidate nanotube radii, extracted from SPE vesicles, enabling quantification of membrane composition and lamellarity. Variances of nanotube radii were measured, showing a growth of 40-56 nm, upon increasing cholesterol content from 0 to 20%. PMID- 22313342 TI - Alveolar recruitment in the delivery room. AB - Most preterm babies with a gestational age less than 23-27 weeks need a respiratory support in the delivery room (DR); the aim of ventilation is to create and maintain a functional residual capacity (FRC); to facilitate gas exchange and to minimize acute lung injury. The application of a continuous positive airway pressure (CPAP) from the first breaths helps in obtaining a lung volume stabilization. Efficacy and safety of the application of a sustained lung inflation (SLI) at birth is still under careful evaluation. The prompt increase of the hearth rate and oxygen saturation in the preliminary studies at the moment available in the literature are signs of the good efficacy of the manoeuvre but the effects of the SLI on oxygenation and hemodynamics are undetermined. When preterm infants need respiratory assistance in the DR, respiratory function monitoring is desirable to apply adequate and gentle resuscitation manoeuvres. Clinical large trials taking place in the DR are needed but they are also extremely difficult to be designed and performed. PMID- 22313343 TI - Child maltreatment, alexithymia, and problematic internet use in young adulthood. AB - The goals of this study were to (a) examine the phenomenology and developmental correlates of problematic Internet use (PIU) in a large and diverse college student sample; (b) evaluate a developmental process model of PIU in which the expected association between child maltreatment and PIU would be explained by alexithymia; and (c) explore these relations as a function of gender and race. PIU was assessed in a sample of 1,470 college students (62.9 percent female, 37.1 percent male; M(age)=19.13 years [SD=1.49]; 46.1 percent Asian, 28.2 percent Hispanic, 16.3 percent White, 5.9 percent Black, and 3.5 percent Multiracial/Other) who participated in a larger study of young adult adaptation, which included measures of child maltreatment, alexithymia, self-concept, social support, and psychopathology. Males and Asian students endorsed higher levels of PIU than females and other ethnoracial groups, respectively. PIU was related to contemporaneous maladaptation in the form of decreased self-concept, lower social support, and increased psychopathology across groups. Experiences of child maltreatment were related to increased PIU, and mediation analyses showed that this relation was partially explained by alexithymia. These relations were comparable across males and females and between Asian and non-Asian respondents. The analyses provide evidence for the significant role of child maltreatment and the cognitive-affective deficits it precipitates in understanding pathways toward PIU in young adulthood. Our findings suggest that maltreated youth are at disproportionate risk for PIU, and their capacities to regulate and process emotion are important targets for prevention and therapeutic intervention. PMID- 22313344 TI - Novel systemic therapeutic for nasopharyngeal carcinoma. AB - INTRODUCTION: Systemic therapy is crucial to the management of locally advanced or metastatic nasopharyngeal cancer (NPC). Despite initial responses, the benefits of conventional chemotherapy are seldom durable and the toxicities are intolerable to most patients. Therefore, novel therapies based on molecular targets of NPC have become the focus of development. AREAS COVERED: Three novel therapeutics, targeting EGFR, angiogenic processes and epigenetic dysregulation, are discussed in this review. The scientific basis and latest published results of clinical trials are also highlighted. EXPERT OPINION: In summary, cetuximab, an anti-EGFR monoclonal antibody shows promising results in both locally advanced and metastatic disease. Anti-angiogenic therapy such as sunitinib is efficacious but hemorrhagic complications are of concern in selected patients. Finally, translational studies demonstrate that epigenetic therapeutics could restore the immunogenicity of Epstein-Barr virus in NPC cells. For anti-EGFR therapy, the promising results in early clinical trials should be validated in Phase III clinical trials. Better selection of patients and safer therapy is necessary in future development of anti-angiogenic therapy for NPC. Early clinical trials on epigenetic therapeutics are in process and results are eagerly awaited. PMID- 22313346 TI - Re-prescribing of causative drugs in persons discharged after serious drug induced upper gastrointestinal bleeding. AB - BACKGROUND: Several drug classes are known to be associated with serious upper gastrointestinal bleeding (UGIB), among others NSAID, low-dose acetylsalicylic acid (ASA), vitamin K antagonists (VKA), clopidogrel and selective serotonin reuptake inhibitors (SSRIs). There are few data on how and to what extent these drugs are reintroduced in patients who have been discharged after a bleeding episode related to any of them. AIM: To assess if physicians re-prescribed potential causative drugs after an episode of UGIB and to explore whether drugs with antihaemostatic action (DAHA) are re-prescribed without a gastro-protective agent. METHODS: By use of the Kaplan-Meyer method, we estimated the time from UGIB to re-prescribing for 3652 cases who were all admitted to hospital with a diagnosis of serious upper gastrointestinal bleeding from 1995 to 2006. Data on drug exposure were retrieved from a Danish prescription database, a recent study on drug-related UGIB, and The National Board of Health in Denmark. RESULTS: One year rates of re-prescribing after UGIB were; 82%, 25%, 43%, 68%, 55%, 71% for SSRIs, NSAID, low-dose ASA, VKA, clopidogrel and dipyridamol, respectively. However, re-prescribing rates without proton pump inhibitors (PPIs) were markedly lower 25%, 3%, 5%, 1%, 17% and 6%, respectively. Non-users of DAHA had a prevalence of PPI use of about 30% a few months after an UGIB. CONCLUSIONS: Drugs with antihaemostatic action are re-prescribed to a large extent after an episode of upper gastrointestinal bleeding, but usually covered by PPIs. This use of PPI is specific for users of drugs with antihaemostatic action. PMID- 22313340 TI - Metabolic abnormalities associated with initiation of systemic treatment for psoriasis: evidence from the Italian Psocare Registry. AB - OBJECTIVE: To evaluate variations in laboratory parameters and diagnoses of selected clinical conditions up to 16 weeks after starting a new systemic psoriasis treatment for Psocare Registry enrollees. DESIGN: Prospective cohort study. SETTING: Italian public referral centres for psoriasis treatment. PATIENTS: First-time recipients (n = 10,539) of continuous systemic psoriasis treatment for at least 16 weeks. MAIN OUTCOME MEASURE: Mean variations in (weeks 8 and 16) and proportions of patients reaching a clinically meaningful increase in serum levels (week 16) of total and low-density lipoprotein cholesterol, triglycerides, aspartate amino transferase, alanine amino transferase and creatinine, as well as week-16 cumulative incidences of new diagnoses of diabetes mellitus and arterial hypertension. RESULTS: Mean cholesterol and triglyceride levels significantly increased in patients treated with acitretin or cyclosporine. Mean triglyceride levels also increased in efalizumab- and etanercept-treated patients. Mean transaminase values increased in methotrexate treated patients, and mean aspartate amino transferase levels increased in infliximab-treated patients. The average serum creatinine value increased in cyclosporine-treated patients. Acitretin and cyclosporine were associated with risk of hypercholesterolaemia (odds ratios 1.51 and 1.34) and acitretin with risk of hypertriglyceridaemia (odds ratio 1.43). Methotrexate and infliximab were associated with risk of more than doubling the upper normal aspartate amino transferase (odds ratios 2.06 and 1.87) and alanine amino transferase (odds ratios 2.38 and 1.74) values. The relative risk of developing arterial hypertension and diabetes was increased for patients receiving cyclosporine (odds ratios 3.31 and 2.88). CONCLUSION: Systemic treatments for psoriasis resulted in heterogeneous effects on the parameters analysed. PMID- 22313348 TI - Women's HIV disclosure to family and friends. AB - Previous researchers have documented rates of HIV disclosure to family at discrete time periods, yet none have taken a dynamic approach to this phenomenon. The purpose of this study is to take the next step and provide a retrospective comparison of rates of women's HIV disclosure to family and friends over a 15 year time span. Of particular interest are the possible influences of social network and relationship characteristics on the time-to-disclosure of serostatus. Time-to-disclosure was analyzed from data provided by 125 HIV-positive women. Participants were primarily married or dating (42%), unemployed (79.2%), African American (68%) women with a high school diploma or less (54.4%). Length of time since diagnosis ranged from 1 month to over 19 years (M=7.1 years). Results pointed to statistically significant differences in time-to-disclosure between family, friends, and sexual partners. Additionally, females and persons with whom the participant had more frequent contact were more likely to be disclosed to, regardless of the type of relationship. The results of this study underscore possible challenges with existing studies which have employed point prevalence designs, and point to new methods which could be helpful in family research. PMID- 22313349 TI - Formation of crystalline Na2V6O16.3H2O ribbons into belts and rings. AB - Single-crystalline nanobelts and nanorings of Na(2)V(6)O(16).3H(2)O structures have been facilely synthesized through a direct hydrothermal reaction between NaVO(3) and H(3)PO(4), without the addition of any harmful solvents or surfactants. The analytical techniques of scanning electron microscopy, transmission electron microscopy (TEM), powder X-ray diffraction, thermogravimetric analysis, energy-dispersive X-ray spectroscopy, Fourier transform infrared, high-resolution TEM, and selected-area electron diffraction have been used to characterize the morphology, composition, and structure of the synthesized products. The Na(2)V(6)O(16).3H(2)O nanobelts are up to several hundreds of micrometers in length and 100-300 nm in thickness, and for nanorings, the diameters are 4.5-6.5 MUm. H(3)PO(4) plays a key role in maintaining the pH of the solution as well as producing PO(4)(3-) ions in solution. The chemical reactions and a possible growth mechanism involved in the formation of Na(2)V(6)O(16).3H(2)O nanobelts and nanorings are briefly discussed. PMID- 22313350 TI - An American response to the Italian guideline on urinary tract infections in young children. PMID- 22313347 TI - Astroglial excitability and gliotransmission: an appraisal of Ca2+ as a signalling route. AB - Astroglial cells, due to their passive electrical properties, were long considered subservient to neurons and to merely provide the framework and metabolic support of the brain. Although astrocytes do play such structural and housekeeping roles in the brain, these glial cells also contribute to the brain's computational power and behavioural output. These more active functions are endowed by the Ca(2+)-based excitability displayed by astrocytes. An increase in cytosolic Ca(2+) levels in astrocytes can lead to the release of signalling molecules, a process termed gliotransmission, via the process of regulated exocytosis. Dynamic components of astrocytic exocytosis include the vesicular plasma membrane secretory machinery, as well as the vesicular traffic, which is governed not only by general cytoskeletal elements but also by astrocyte-specific IFs (intermediate filaments). Gliotransmitters released into the ECS (extracellular space) can exert their actions on neighbouring neurons, to modulate synaptic transmission and plasticity, and to affect behaviour by modulating the sleep homoeostat. Besides these novel physiological roles, astrocytic Ca(2+) dynamics, Ca(2+)-dependent gliotransmission and astrocyte neuron signalling have been also implicated in brain disorders, such as epilepsy. The aim of this review is to highlight the newer findings concerning Ca(2+) signalling in astrocytes and exocytotic gliotransmission. For this we report on Ca(2+) sources and sinks that are necessary and sufficient for regulating the exocytotic release of gliotransmitters and discuss secretory machinery, secretory vesicles and vesicle mobility regulation. Finally, we consider the exocytotic gliotransmission in the modulation of synaptic transmission and plasticity, as well as the astrocytic contribution to sleep behaviour and epilepsy. PMID- 22313351 TI - Replication bypass of the trans-4-Hydroxynonenal-derived (6S,8R,11S)-1,N(2) deoxyguanosine DNA adduct by the sulfolobus solfataricus DNA polymerase IV. AB - trans-4-Hydroxynonenal (HNE) is the major peroxidation product of omega-6 polyunsaturated fatty acids in vivo. Michael addition of the N(2)-amino group of dGuo to HNE followed by ring closure of N1 onto the aldehyde results in four diastereomeric 1,N(2)-dGuo (1,N(2)-HNE-dGuo) adducts. The (6S,8R,11S)-HNE-1,N(2) dGuo adduct was incorporated into the 18-mer templates 5'-d(TCATXGAATCCTTCCCCC) 3' and d(TCACXGAATCCTTCCCCC)-3', where X = (6S,8R,11S)-HNE-1,N(2)-dGuo adduct. These differed in the identity of the template 5'-neighbor base, which was either Thy or Cyt, respectively. Each of these templates was annealed with either a 13 mer primer 5'-d(GGGGGAAGGATTC)-3' or a 14-mer primer 5'-d(GGGGGAAGGATTCC)-3'. The addition of dNTPs to the 13-mer primer allowed analysis of dNTP insertion opposite to the (6S,8R,11S)-HNE-1,N(2)-dGuo adduct, whereas the 14-mer primer allowed analysis of dNTP extension past a primed (6S,8R,11S)-HNE-1,N(2)-dGuo:dCyd pair. The Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) belongs to the Y family of error-prone polymerases. Replication bypass studies in vitro reveal that this polymerase inserted dNTPs opposite the (6S,8R,11S)-HNE-1,N(2)-dGuo adduct in a sequence-specific manner. If the template 5'-neighbor base was dCyt, the polymerase inserted primarily dGTP, whereas if the template 5'-neighbor base was dThy, the polymerase inserted primarily dATP. The latter event would predict low levels of Gua -> Thy mutations during replication bypass when the template 5' neighbor base is dThy. When presented with a primed (6S,8R,11S)-HNE-1,N(2) dGuo:dCyd pair, the polymerase conducted full-length primer extension. Structures for ternary (Dpo4-DNA-dNTP) complexes with all four template-primers were obtained. For the 18-mer:13-mer template-primers in which the polymerase was confronted with the (6S,8R,11S)-HNE-1,N(2)-dGuo adduct, the (6S,8R,11S)-1,N(2) dGuo lesion remained in the ring-closed conformation at the active site. The incoming dNTP, either dGTP or dATP, was positioned with Watson-Crick pairing opposite the template 5'-neighbor base, dCyt or dThy, respectively. In contrast, for the 18-mer:14-mer template-primers with a primed (6S,8R,11S)-HNE-1,N(2) dGuo:dCyd pair, ring opening of the adduct to the corresponding N(2)-dGuo aldehyde species occurred. This allowed Watson-Crick base pairing at the (6S,8R,11S)-HNE-1,N(2)-dGuo:dCyd pair. PMID- 22313352 TI - Validity, reliability, and responsiveness of a self-reported foot and ankle score (SEFAS). AB - BACKGROUND AND PURPOSE: A questionnaire was introduced by the New Zealand Arthroplasty Registry for use when evaluating the outcome of total ankle replacement surgery. We evaluated the reliability, validity, and responsiveness of the modified Swedish version of the questionnaire (SEFAS) in patients with osteoarthritis or inflammatory arthritis before and/or after their ankle was replaced or fused. PATIENTS AND METHODS: The questionnaire was translated into Swedish and cross-culturally adapted according to a standardized procedure. It was sent to 135 patients with ankle arthritis who were scheduled for or had undergone surgery, together with the foot and ankle outcome score (FAOS), the short form 36 (SF-36) score, and the EuroQol (EQ-5D) score. Construct validity was evaluated with Spearman's correlation coefficient when comparing SEFAS with FAOS, SF-36, and EQ-5D, content validity by calculating floor and ceiling effects, test-retest reliability with intraclass correlation coefficient (ICC), internal consistency with Cronbach's alpha (n = 62), agreement by Bland-Altman plot, and responsiveness by effect size and standardized response mean (n = 37). RESULTS: For construct validity, we correlated SEFAS with the other scores and 70% or more of our predefined hypotheses concerning correlations could be confirmed. There were no floor or ceiling effects. ICC was 0.92 (CI 95%: 0.88 0.95), Cronbach's alpha 0.96, effect size was 1.44, and the standardized response mean was 1.00. INTERPRETATION: SEFAS is a self-reported foot and ankle score with good validity, reliability and responsiveness, indicating that the score can be used to evaluate patients with osteoarthritis or inflammatory arthritis of the ankle and outcome of surgery. PMID- 22313353 TI - Specific detection of potentially allergenic peach and apple in foods using polymerase chain reaction. AB - Two PCR methods were developed for specific detection of the trnS-trnG intergenic spacer region of Prunus persica (peach) and the internal transcribed spacer region of Malus domestica (apple). The peach PCR amplified a target-size product from the DNA of 6 P. persica cultivars including 2 nectarine and 1 flat peach cultivar, but not from those of 36 nontarget species including 6 Prunus and 5 other Rosaceae species. The apple PCR amplified a target-size product from the DNA of 5 M. domestica cultivars, but not from those of 41 nontarget species including 7 Maloideae and 9 other Rosaceae species. Both methods detected the target DNA from strawberry jam and cookies spiked with peach and apple at a level equivalent to about 10 MUg of total soluble proteins of peach or apple per gram of incurred food. The specificity and sensitivity were considered to be sufficient for the detection of trace amounts of peach or apple contamination in processed foods. PMID- 22313354 TI - RNA unwinding from reweighted pulling simulations. AB - The forming and melting of complementary base pairs in RNA duplexes are conformational transitions required to accomplish a plethora of biological functions. Yet the dynamic steps of these transitions have not been quantitatively characterized at the molecular level. In this work, the base opening process was first enforced by atomistic pulling simulations and then analyzed with a novel reweighting scheme, which allowed the free-energy profile along any suitable reaction coordinate, for example, solvation, to be reconstructed. The systematic application of such approach to different base-pair combinations provides a molecular motion picture of helix opening, which is validated by comparison with an extensive set of experimental observations and links them to the enzyme-dependent unwinding mechanism. The RNA intrinsic dynamics disclosed in this work could rationalize the directionality observed in RNA-processing molecular machineries. PMID- 22313355 TI - Mycobacterium szulgai tenosynovitis: a fishy tale. PMID- 22313356 TI - Impact of epilepsy surgery on seizure control and quality of life: a 26-year follow-up study. AB - PURPOSE: The short-term efficacy and safety of epilepsy surgery relative to medical therapy has been established, but it remains underutilized. There is a lack of data regarding the long-term seizure-control rates and quality of life outcomes after epilepsy surgery. This study represents the longest follow-up study to date, with a mean follow-up duration of 26 years. METHODS: We studied the seizure and health-related quality of life outcomes of patients who underwent epilepsy surgery by Dr. Sidney Goldring from 1967 to 1990. Retrospective clinical chart reviews gathered perioperative data and surveys obtained follow-up data. Seizure outcome was evaluated using the Engel classification system. KEY FINDINGS: Of 361 patients, 117 (32.4%) completed follow-up interviews. Fifty-six patients (48%) were Engel class I. Mean overall Quality of Life in Epilepsy (QOLIE-31) questionnaire score for the cohort was 68.2 +/- 16. Eighty percent of patients reported their overall quality of life now as being better than before surgery. Seizure freedom was associated with better quality of life. We did not observe a statistically significant association between postoperative complications and long-term outcome. Patients who underwent temporal lobe resection achieved better seizure outcomes than those who underwent other types of procedures. Astatic seizures and bilateral surgery were associated with a worse Engel class outcome. SIGNIFICANCE: Our study demonstrates that the beneficial effects of epilepsy surgery are sustained over decades, and that these beneficial effects are correlated with an improved quality of life. The confirmation of its durability makes us optimistic that the outcomes from modern epilepsy surgery will be even better and that our present enthusiasm for this treatment modality is not misplaced. PMID- 22313357 TI - Unique features of PTCH1 mutation spectrum in Chinese sporadic basal cell carcinoma. AB - BACKGROUND: Alterations of the PTCH1 gene have been found to contribute to both familial and sporadic basal cell carcinoma (BCC), especially in Caucasian patients. Furthermore, the majority of PTCH1 gene mutations in sporadic BCCs in Caucasian patients carry ultraviolet (UV) signatures, suggesting the key role of UV light in BCC development. However, sporadic BCC in non-Caucasian population has a lower incidence, and the pathogenesis remains largely unknown. To date, there has been no mutation analysis on PTCH1 gene in Chinese patients with sporadic BCCs. OBJECTIVE: To investigate genetic alterations of the PTCH1 gene in Chinese sporadic BCCs. METHODS: Direct sequencing was used to screen for mutations in PTCH1 in 31 microdissected samples in Chinese sporadic BCCs. In addition, single nucleotide polymorphisms (SNPs) were studied for loss of heterozygosity (LOH). RESULTS: Nineteen PTCH1 mutations in 17 of the 31 BCCs (54.8%) were identified. SNP analysis revealed LOH of PTCH1 in 10 of 23 BCCs (43.5%). Interestingly, the majority of mutations identified (63.2%) were insertion/deletion, which was different from the results in Caucasian cases whose mutations are predominantly point mutations. Only two (10.5%) of the remaining seven mutations were UV-specific C -> T transition or tandem CC -> TT transitions. All mutations occurred evenly throughout the entire PTCH1 protein domain without a hot-spot detected. CONCLUSION: Mutations and LOH in PTCH1 were also highly prevalent in Chinese sporadic BCCs. However, UV light plays a less role in causing these mutations, suggesting other potential mechanisms in the development of sporadic BCC in Chinese patients. PMID- 22313358 TI - The prevalence of problematic video gamers in the Netherlands. AB - This study surveyed Dutch adolescents and adults about their video gaming behavior to assess the prevalence of problematic gaming. A representative national panel of 902 respondents aged 14 to 81 took part in the study. The results show that gaming in general is a wide-spread and popular activity among the Dutch population. Browser games (small games played via the internet) and offline casual games (e.g., offline card games) were reported as most popular type of game. Online games (e.g., massively multiplayer online role-playing games) are played by a relatively small part of the respondents, yet considerably more time is spent on these online games than on browser games, offline casual games, and offline games (e.g., offline racing games). The prevalence of problematic gaming in the total sample is 1.3 percent. Among adolescents and young adults problematic gaming occurs in 3.3 percent of cases. Particularly male adolescents seem to be more vulnerable to developing problematic gaming habits. PMID- 22313359 TI - MCL1 down-regulation plays a critical role in mediating the higher anti-leukaemic activity of the multi-kinase inhibitor Sorafenib with respect to Dasatinib. PMID- 22313360 TI - Novel report of expression and function of CD97 in malignant gliomas: correlation with Wilms tumor 1 expression and glioma cell invasiveness. AB - OBJECT: The Wilms tumor 1 (WT1) protein-a developmentally regulated transcription factor-is aberrantly expressed in gliomas and promotes their malignant phenotype. However, little is known about the molecular allies that help it mediate its oncogenic functions in glioma cells. METHODS: The authors used short interfering RNA (siRNA) to suppress WT1 expression in glioblastoma (GBM) cells and evaluated the effect of this on GBM cell invasiveness. Gene expression analysis was then used to identify the candidate genes that were altered as a result of WT1 silencing. One candidate target, CD97, was then selected for further investigation into its role by suppressing its expression using siRNA silencing, followed by proliferation and invasion assays. RESULTS: WT1 levels were reliably and reproducibly suppressed by siRNA application. This resulted in a significant decrease in cellular invasiveness. Microarray analyses identified the gene products that were consistently downregulated (27) and upregulated (11) with WT1 silencing. Of these, CD97 expression was consistently suppressed across the 3 different GBM cell lines studied and was found on further investigation to significantly impact GBM cell invasiveness. CONCLUSIONS: Although CD97 expression in gliomas has not been described previously, we conclude that the possible upregulation of CD97 mediated by WT1 promotes cellular invasiveness-one of the most characteristic and challenging aspects of glial tumor cells. Further studies are needed to clarify the nature of this regulation and its impact, as CD97 could represent a novel target for antiglioma therapies. PMID- 22313361 TI - Boxing and mixed martial arts: preliminary traumatic neuromechanical injury risk analyses from laboratory impact dosage data. AB - OBJECT: In spite of ample literature pointing to rotational and combined impact dosage being key contributors to head and neck injury, boxing and mixed martial arts (MMA) padding is still designed to primarily reduce cranium linear acceleration. The objects of this study were to quantify preliminary linear and rotational head impact dosage for selected boxing and MMA padding in response to hook punches; compute theoretical skull, brain, and neck injury risk metrics; and statistically compare the protective effect of various glove and head padding conditions. METHODS: An instrumented Hybrid III 50th percentile anthropomorphic test device (ATD) was struck in 54 pendulum impacts replicating hook punches at low (27-29 J) and high (54-58 J) energy. Five padding combinations were examined: unpadded (control), MMA glove-unpadded head, boxing glove-unpadded head, unpadded pendulum-boxing headgear, and boxing glove-boxing headgear. A total of 17 injury risk parameters were measured or calculated. RESULTS: All padding conditions reduced linear impact dosage. Other parameters significantly decreased, significantly increased, or were unaffected depending on padding condition. Of real-world conditions (MMA glove-bare head, boxing glove-bare head, and boxing glove-headgear), the boxing glove-headgear condition showed the most meaningful reduction in most of the parameters. In equivalent impacts, the MMA glove-bare head condition induced higher rotational dosage than the boxing glove-bare head condition. Finite element analysis indicated a risk of brain strain injury in spite of significant reduction of linear impact dosage. CONCLUSIONS: In the replicated hook punch impacts, all padding conditions reduced linear but not rotational impact dosage. Head and neck dosage theoretically accumulates fastest in MMA and boxing bouts without use of protective headgear. The boxing glove headgear condition provided the best overall reduction in impact dosage. More work is needed to develop improved protective padding to minimize linear and rotational impact dosage and develop next-generation standards for head and neck injury risk. PMID- 22313362 TI - The broad-leaf herbicide 2,4-dichlorophenoxyacetic acid turns rice into a living trap for a major insect pest and a parasitic wasp. AB - Synthetic chemical elicitors of plant defense have been touted as a powerful means for sustainable crop protection. Yet, they have never been successfully applied to control insect pests in the field. We developed a high-throughput chemical genetics screening system based on a herbivore-induced linalool synthase promoter fused to a beta-glucuronidase (GUS) reporter construct to test synthetic compounds for their potential to induce rice defenses. We identified 2,4 dichlorophenoxyacetic acid (2,4-D), an auxin homolog and widely used herbicide in monocotyledonous crops, as a potent elicitor of rice defenses. Low doses of 2,4-D induced a strong defensive reaction upstream of the jasmonic acid and ethylene pathways, resulting in a marked increase in trypsin proteinase inhibitor activity and volatile production. Induced plants were more resistant to the striped stem borer Chilo suppressalis, but became highly attractive to the brown planthopper Nilaparvata lugens and its main egg parasitoid Anagrus nilaparvatae. In a field experiment, 2,4-D application turned rice plants into living traps for N. lugens by attracting parasitoids. Our findings demonstrate the potential of auxin homologs as defensive signals and show the potential of the herbicide to turn rice into a selective catch crop for an economically important pest. PMID- 22313363 TI - Superheating water by CW excitation of gold nanodots. AB - A temperature-dependent photoluminescent thin film of Al(0.94)Ga(0.06)N doped with Er(3+) is used to measure the temperature of lithographically prepared gold nanodots. The gold nanodots and thin film are excited simultaneously with a continuous wave (CW) Nd:YAG 532 nm laser. The gold nanodot is submersed under water, and the dot is subsequently heated. The water immediately surrounding the nanodot is superheated beyond the boiling point up to the spinodal decomposition temperature at 594 +/- 17 K. The spinodal decomposition has been confirmed with the observation of critical opalescence. We characterize the laser scattering that occurs in unison with spinodal decomposition due to an increased coherence length associated with the liquid-liquid transition. PMID- 22313364 TI - Single course of antenatal steroids did not alter cortisol in preterm infants up to 18 months. AB - AIMS: To determine whether a single course of antenatal dexamethasone alters resting cortisol at 3, 8 and 18 months corrected age in preterm infants. METHODS: Preterm infants born <=32 weeks gestational age were recruited during 2001-2004 from a single neonatal intensive care unit. Resting salivary cortisol was collected at least once at 3, 8 and 18 months corrected age in a longitudinal cohort. A mixed-effects repeated measures analysis was used to accommodate cases with less than complete follow-up. RESULTS: One hundred and thirty three infants were included in the present study, contributing 266 cortisol samples. Of these, 107 infants had been exposed to a single course of antenatal dexamethasone and 26 not exposed to antenatal steroids. There was no significant main effect of antenatal steroids on resting cortisol at any age. This result was not altered after adjusting for gestational age at birth, neonatal cumulative pain, morphine exposure, mechanical ventilation days and post-natal steroid exposure. CONCLUSIONS: No effect of a single course of dexamethasone on resting salivary cortisol, an indicator of hypothalamic-pituitary-adrenal axis function, was found in infancy up to 18 months corrected age in infants born very preterm. PMID- 22313365 TI - Characterization of and functional evidence for Ste27 of Streptomyces sp. 139 as a novel spermine/spermidine acetyltransferase. AB - Ebosin, a novel exopolysaccharide produced by Streptomyces sp. 139, has remarkable anti-rheumatoid arthritis activity in vivo and its biosynthesis gene cluster (ste) consists of 27 ORFs (open reading frames). The present paper reports our study of the protein product encoded by ste27. Database searching reveals the homology of Ste27 with some spermidine/spermine acetyltransferases. To confirm the prediction, the ste27 gene was cloned and expressed in Escherichia coli BL21(DE3) cells and recombinant Ste27 was purified. The following enzymatic analysis revealed its ability of transferring the acetyl group from acetyl-CoA to spermidine and spermine, with spermidine being the preferred substrate. Ste27 can acetylate the N1, N4 and N8 positions on spermidine. The Km values of Ste27 were determined for spermidine and spermine, as well as for acetyl-CoA, poly-L-lysine and glucosamine 6-phosphate. Upon gene knockout, the exopolysaccharide-27m produced by the mutant strain Streptomyces sp. 139 (ste27-), compared with Ebosin, exhibited a significantly reduced binding activity to the interleukin-1 receptor. After gene complementation, the binding activity was partially restored. This demonstrated that the ste27 gene is involved in the biosynthesis of Ebosin. Molecular modelling was also carried out to predict the binding mode of Ste27 with acetyl-CoA, spermidine or spermine. PMID- 22313366 TI - Do fathead minnows, Pimephales promelas Rafinesque, alter their club cell investment in responses to variable risk of infection from Saprolegnia? AB - Fish in the Superorder Ostariophysi possess large epidermal club cells that release chemical cues warning nearby conspecifics of danger. Despite the long held assumption that such club cells evolved under the selective force of predation, recent studies demonstrated that predation has no effect on club cell investment. Rather, club cells have an immune function and cell production may be stimulated by skin-penetrating pathogens and parasites. The current work investigates whether fathead minnows, Pimephales promelas, alter their club cell characteristics based on variation in infection risk. In a 2 * 3 design, we exposed minnows to infective cysts of two oomycete species (Saprolegnia ferax and S. parasitica) at three different concentrations (2, 20 or 200 cysts L(-1)). Club cell characteristics (number and size) were quantified 12 days after exposure. Saprolegnia parasitica is thought to be more pathogenic than S. ferax, hence we predicted greater club cell investment and a larger turnover rate of cells by minnows exposed to S. parasitica than S. ferax. We also predicted that minnows exposed to higher numbers of cysts should invest more in club cells and have a higher turnover rate of cells. We found no difference in club cell density or size between fish exposed to the two Saprolegnia species; however, fish exposed to high concentrations of pathogens had smaller club cells than those exposed to low concentrations, indicating a higher rate of turnover of cells in the epidermis. PMID- 22313367 TI - Genome-wide copy number analysis in primary breast cancer. AB - INTRODUCTION: Carcinogenesis is considered to be a multistep process that may involve cumulative genomic alterations. Loss of chromosomal material would inactivate tumor suppressor genes and gain of chromosomal material has the potential to activate tumor-promoting genes. AREAS COVERED: Recent intensive studies by array comparative genomic hybridization (aCGH) have demonstrated frequent alterations in multiple regions of the genome. This suggests that these regions contain a variety of oncogenes and tumor suppressor genes associated with breast cancer development. The patterns of copy number variations (CNVs) have been suggested to be associated with breast cancer subtypes, indicating the importance of genomic instability in the development of breast cancer. EXPERT OPINION: To further clarify the complexity of gene alterations, one approach is to employ a CNV-targeted platform that harbors a large number of direct CNV markers located in the repeat-rich unstable regions of the human genome. Next generation sequencing is another approach to overcome the limitations of aCGH such as the repeat-rich regions. Genomic analysis should be combined with expression analysis to elucidate individual genes relevant to breast cancer development and progression. The elucidation of the functions of the affected genes would lead to identification of new molecular targets for breast cancer eradication. PMID- 22313368 TI - Early recovery after fast-track Oxford unicompartmental knee arthroplasty. 35 patients with minimal invasive surgery. AB - BACKGROUND AND PURPOSE: After total knee arthroplasty with conventional surgical approach, more than half of the quadriceps extension strength is lost in the first postoperative month. Unicompartmental knee arthroplasty (UKA) operated with minimally invasive surgery (MIS) results in less operative trauma. We investigated changes in leg-extension power (LEP) in the first month after MIS Oxford UKA and its relation to pain, knee motion, functional performance, and knee function. PATIENTS AND METHODS: In 35 consecutive Oxford UKA patients, LEP was measured 1 week before and 1 month after surgery together with knee motion, knee swelling, the 30-second chair-stand test, and Oxford knee score. Assessment of knee pain at rest and walking was done using a visual analog scale. RESULTS: 30 patients were discharged on the day after surgery, and 5 on the second day after surgery. LEP and functional performance reached the preoperative level after 1 month. Only slight postoperative knee swelling was observed with rapid restoration of knee flexion and function. A high level of pain during the first postoperative night and day fell considerably thereafter. None of the patients needed physiotherapy supervision in the first month after discharge. INTERPRETATION: Fast-track MIS Oxford UKA with discharge on the day after surgery is safe and leads to early recovery of knee motion and strength even when no physiotherapy is used. PMID- 22313370 TI - Pyrazolium- and 1,2-cyclopentadiene-based ligands as sigma-donors: a theoretical study of electronic structure and bonding. AB - A high-level theoretical investigation of 1,2-cyclopentadiene (4) was performed using density functional theory and wave function methods. The results reveal that, in contrast to earlier assumptions, the ground state of this ephemeral "allene" is carbene-like with a small diradical component. Furthermore, the electronic structure and chemistry of 4 are found to parallel that of 1,2,4,6 cycloheptatetraene: both molecules possess a low-lying excited singlet state with a closed-shell carbenic structure, enabling rich coordination chemistry. Energy decomposition analyses conducted for currently unknown metal complexes of 4 as well as those involving stable carbenes based on the pyrazolium framework (aka "bent allenes" or remote N-heterocyclic carbenes) indicate that all investigated ligands form particularly strong metal-carbon bonds. Most notably, without exocyclic pi-type substituents, 4 and pyrazolin-4-ylidenes are the strongest donor ligands examined, in large part because of the energy and shape of their highest occupied molecular orbital. As a whole, the current work opens a new chapter in the chemistry of 1,2-cyclopentadiene, which is hoped to spark renewed interest among experimentalists. In addition, results from the conducted bonding analyses underline that more emphasis should be placed on purely carbocyclic carbenes as unprecedented sigma-donor strengths can be realized through this route. PMID- 22313369 TI - Pravastatin reduces steroid-induced osteonecrosis of the femoral head in SHRSP rats. AB - BACKGROUND AND PURPOSE: Although the definite cause of steroid-induced osteonecrosis of the femoral head (ONFH) is unknown, peripheral circulatory failure, lipid metabolism disturbance, and increased oxidative stress are considered to be possible causes. We investigated whether pravastatin as a statin treatment reduces (1) the incidence of ONFH, (2) the adipocyte area, and (3) bone marrow changes in the femoral head. METHODS: We divided up 81 thirteen-week-old spontaneously hypertensive stroke-prone (SHRSP)/Izm male rats into 4 groups: a control group (group C), a group given pravastatin (group P), a group given steroid (group S), and a group given both pravastatin and steroid (Group PS). The steroid was administered at 15 weeks of age. Pravastatin, as a statin, was administered in the drinking water for 4 weeks. The rats were killed when 17 weeks old. Osteonecrosis was diagnosed based on histopathological examination. Oxidative stress was assessed from immunostaining. RESULTS: The incidence of histological osteonecrosis was lower in the groups given pravastatin. The percentage of adipocyte area in the bone marrow was lower in the PS group than in the S group. Immunohistochemical staining for oxidative stress showed that staining was less in the PS group than in the S group. Pravastatin had no effect on the blood-derived biochemical findings on lipid metabolism. However, it reduced the incidence of steroid-induced ONFH in these SHRSP rats. We presume that this occurred by reducing oxidative stress and by reducing the percentage of adipocyte area in the femoral heads. INTERPRETATION: Our data suggest that pravastatin may be effective in reducing steroid-induced ONFH. PMID- 22313371 TI - Molecular-level characterization of the breathing behavior of the jungle-gym-type DMOF-1 metal-organic framework. AB - Fundamental insights into the molecular mechanisms that determine the breathing behavior of the jungle-gym-type DMOF-1 metal-organic framework upon adsorption of benzene and isopropyl alcohol are gained from computer simulations. In all cases, good agreement is obtained between the calculated and experimental structural parameters. In the case of benzene adsorption, DMOF-1 is predicted to exist in a narrow pore configuration at high loadings and/or low temperature. A structural transition into a large pore configuration is then observed as the temperature increases and/or the loading decreases, which is directly related to the spatial distribution and molecular interactions of the benzene molecules within the pores. The isopropyl alcohol adsorption simulations indicate that DMOF-1 undergoes two distinct structural transitions (from large pore to narrow pore and then back to large pore) as the number of adsorbed molecules increases, which is explained in terms of the formation of hydrogen bonds between the isopropyl molecules and the framework. PMID- 22313372 TI - Isolation and characterization of two endoxylanases from Fusarium graminearum. AB - This paper reports the first isolation from cultures of two endoxylanases secreted by Fusarium graminearum Schwabe [teleomorph Gibberella zeae (Schweinitz) Petch]. When F. graminearum is grown on wheat bran hydrated with a modified synthetic medium, high xylanase activity can be extracted. The two endoxylanases were identified by LC-MS/MS as the products of genes FGSG_6445 (Genbank gene id 2788192 ) (xylanase 1) and FGSG_3624 (GenBank accession no. AJ863566 ) (xylanase 2) with 61 and 51% sequence coverage, respectively. Both enzymes showed a pH optimum at pH 6, with xylanase 1 exhibiting a wider active pH range (5.5-9) than xlylanase 2 (5.5-7.5). Their temperature dependences were similar, >60% between 35 and 60 degrees C, with optimal temperatures of 45 degrees C for xylanase 1 and 50 degrees C for xylanase 2. Kinetic studies found that both enzymes had a lower K(m) for linear beachwood xylan than arabinoxylan. For xylanase 2, the V(max) increased with arabinoxylan, but decreased for xylanase 1. PMID- 22313373 TI - Manifold implications of forgotten hyperglycemia in clinical opiate dependence. AB - Both chronic opiate dependence and diabetes are widespread public health problems. The historically causal relationship between opiate pharmacology and hyperglycemia would appear to have fallen from current medical knowledge. The aims of this study were to assess the severity of hyperglycemia in our opiate substance use disorder (SUD) patient population and review its pathophysiological basis. A review was undertaken of our clinical pathology database, comparing SUD patients and general medical controls (NSUD). A total of 1,602 SUD patients were compared with 2,858 NSUD patients 15-50 years of age. Mean ages were 31.29 +/- 7.40 and 31.55 +/- 9.17 years, respectively (P = 0.42) and were 68.60 and 52.76% male (P < 0.0001). The glycosylated hemoglobin (HbA1c) level in diabetics was 8.14 +/- 2.76 and 6.29 +/- 1.88 (P = 0.0032). In a nested case-control subset, random glucose, HbA1c, and fructosamine levels were all significantly elevated (P < 0.05). Adjusted for age, the HbA1c level was elevated among the SUD group (P < 0.0001) the age at addiction interaction was also significant (P < 0.0001). Serum glucose, HbA1c, fructosamine, and microalbumin levels were shown to be biomarkers of age. At multiple regression analysis, interactions between age, addictive status, glycemia, and the inflammatory markers, ethrocyte sedimentation rate and C-reactive protein, were significant (P < 0.05). At age 50, diabetic SUD patients had a HbA1c of 8.31%, which was equivalent to that of NSUD patients at age 140.54 years, a 181.07% elevation. These results confirm that hyperglycemia is higher in both an absolute and an age-dependent sense among diabetic SUD patients. These results are consistent with an acceleration of age-related and degenerative pathologies in many tissues and therefore carry far-reaching implications for the safety of indefinite opiate maintenance. PMID- 22313374 TI - The homozygous mutation G75R in the human SLC11A2 gene leads to microcytic anaemia and iron overload. PMID- 22313375 TI - 3D nanoporous nanowire current collectors for thin film microbatteries. AB - Conventional thin film batteries are fabricated based on planar current collector designs where the high contact resistance between the current collector and electrodes impedes overall battery performance. Hence, current collectors based on 3D architectures and nanoscale roughness has been proposed to dramatically increase the electrode-current collector surface contact areas and hence significantly reduce interfacial resistance. The nanorod-based current collector configuration is one of several 3D designs which has shown high potential for the development of high energy and high power microbatteries in this regard. Herein we fabricate a nanoporous nanorod based current collector, which provides increased surface area for electrode deposition arising from the porosity of each nanorods, yet keeping an ordered spacing between nanorods for the deposition of subsequent electrolyte and electrode layers. The new nanostructured 3D current collector is demonstrated with a polyaniline (PANI)-based electrode system and is shown to deliver improved rate capability characteristics compared to planar configurations. We have been able to achieve stable capacities of ~32 MUAh/cm(2) up to 75 cycles of charge/discharge even at a current rate of ~0.04 mA/cm(2) and have observed good rate capability even at high current rates of ~0.8 mA/cm(2). PMID- 22313376 TI - Multiple generations of carbon in the apex chert and implications for preservation of microfossils. AB - While the Apex chert is one of the most well-studied Archean deposits on Earth, its formation history is still not fully understood. Here, we present Raman spectroscopic data collected on the carbonaceous material (CM) present within the matrix of the Apex chert. These data, collected within a paragenetic framework, reveal two different phases of CM deposited within separate phases of quartz matrix. These multiple generations of CM illustrate the difficulty of searching for signs of life in these rocks and, by extension, in other Archean sequences. PMID- 22313377 TI - Outcome and complications of endoscopic ultrasound guided pancreatic pseudocyst drainage using combined endoprosthesis and naso-cystic drain. AB - BACKGROUND AND AIM: Endoscopic ultrasound guided pancreatic pseudocyst drainage (EUS-PPD) is increasingly being used for management of pancreatic pseudocysts. We evaluated the outcome and complications of EUS-PPD with modified combined technique by inserting both endoprosthesis and naso-cystic drain. METHODS: Forty patients referred between August 2007 and January 2010 for EUS-PPD were prospectively studied. EUS-PPD was attempted for symptomatic pancreatic pseudocysts which were; (i) resistant to conservative treatment, (ii) in contact with the gastric or duodenal wall on EUS and (iii) having no bulge seen on endoscopy. Controlled radial expansion wire guided balloon dilation of the puncture tract was performed followed by insertion of a 10 French double pigtail stent and 7-Fr naso-biliary drain. The early and late outcome and complications of EUS-PPD were analyzed. RESULTS: Thirty-two patients had non-infected and eight had infected pseudocysts. EUS-PPD was technically successful in all. Pseudocysts resolved completely in 39 patients, while one with infected pseudocyst underwent surgical resection for bleeding in the cyst. Naso-cystic drain was removed in 39 patients after median duration of 13 days. Thereafter, the double pigtail stent was removed in all cases after median duration of 10 weeks. Pseudocyst recurred in one patient requiring a second session of EUS-PPD. All 32 patients without cystic infection were successfully treated by EUS-PPD. Seven out of eight patients (87%) with cystic infection were successfully treated by EUS-PPD. CONCLUSION: Endoscopic ultrasound guided pancreatic pseudocyst drainage with modified combined technique is safe and is associated with high success rate. PMID- 22313378 TI - Critical appraisal of maxillary swing approach for nasopharyngeal carcinoma. AB - BACKGROUND: The aim of the current study was to report results of salvage nasopharyngectomy using the maxillary swing approach for persistent or recurrent nasopharyngeal carcinoma after primary treatment. METHODS: Between 1989 and 2011, Nasopharyngectomies were performed in 312 patients. Data were composed of retrospective review of records of the first 72 patients followed by a prospective collection of data for the remaining patients. RESULTS: Among the patients, 41 (13.1%) had persistent tumours and 271 (86.9%) had recurrent disease. Curative resection was achieved in 248 (79.5%) patients. All patients survived the operations. The median follow up duration was 34 months. The overall 5-year actuarial local tumour control was 74% and the overall 5-year disease-free survival was 56%. Those with negative resection margins on frozen section and tumour size less than 1.5 cm in diameter had significantly better local tumour control in the nasopharynx as well as disease-free survival. CONCLUSIONS: Maxillary swing nasopharyngectomy is an effective salvage procedure for small, persistent or recurrent tumour in the nasopharynx after primary therapy. PMID- 22313379 TI - Pathology of demyelinating diseases. AB - There has been significant progress in our understanding of the pathology and pathogenesis of central nervous system inflammatory demyelinating diseases. Neuropathological studies have provided fundamental new insights into the pathogenesis of these disorders and have led to major advances in our understanding of multiple sclerosis (MS) heterogeneity, the substrate of irreversible progressive disability in MS, the relationship between inflammation and neurodegeneration in MS, the neuroimaging correlates of MS lesions, and the pathogenesis of other central nervous system inflammatory disorders, including neuromyelitis optica, acute disseminated encephalomyelitis, and Balo's concentric sclerosis. Herein, we review the pathological features of these central nervous system inflammatory demyelinating disorders and discuss neuropathological studies that have yielded novel insights into potential mechanisms involved in the formation of the demyelinated lesion. PMID- 22313380 TI - BaAu(x)Zn(13-x): electron-poor cubic NaZn13-type intermetallic and its ordered tetragonal variant. AB - Cubic NaZn(13)-type (Fm-3c, Z = 8) BaAu(x)Zn(13-x) compounds in the regions 1 <= x <= 5.4 (a = 12.418(1)-12.590(1) A) and 6.4 <= x <= 8 (a = 12.630(1)-12.660(1) A) plus an ordered tetragonal variant near x = 6 (P4/nbm; a = 8.8945(4) A, c = 12.646(1) A; Z = 4) have been synthesized and characterized by means of X-ray diffraction. Although the cubic structure contains Zn-centered, mixed (Zn, Au) icosahedra connected in alternate orientations via mixed tetrahedral stars (TS), the icosahedron vertices are ordered in the tetragonal structure. Both the inner and the outer tetrahedra in the TS in the cubic phase consist of mixed Au and Zn atoms, whereas the tetragonal phase features three different coloring schemes: inner Zn and outer Au tetrahedra, vice versa, or mixed Au and Zn sites on both inner and outer tetrahedra. Barium atoms center 24-atom snub cuboctahedra. Ordering of Au and Zn in the tetragonal phase achieves the largest number of heteroatomic Au-Zn contacts and yields relatively larger Hamilton populations ( ICOHPs) compared with homoatomic counterparts according to LMTO-based electronic structure calculations and analysis. Larger overlap populations are also observed for inter- versus intraicosahedral interactions. The densities-of-states data suggest the phase is metallic with highly dispersed Au d bands and nearly free electron-like s and p bands for both Au and Zn. PMID- 22313381 TI - Developmentally equivalent tissue sampling based on growth kinematic profiling of Arabidopsis inflorescence stems. AB - * Directional growth in Arabidopsis thaliana during bolting of the inflorescence stem makes this an attractive system for study of the underlying processes of tissue elongation and cell wall extension. Analysis of local molecular events accompanying Arabidopsis inflorescence stem elongation is hampered by difficulties in isolating developmentally matched tissue samples from different plants. * Here, we present a novel sampling approach in which specific developmental stages along the developing stem are defined nonintrusively in terms of their relative elemental growth rate by use of time-lapse imagery and subsequent derivation of growth kinematic profiles for individual plants. * Growth kinematic profiling reveals that key developmental transitions such as the point of maximum elongation rate and the point of cessation of elongation occur over broad and overlapping ranges across individuals within a population of the Columbia (Col-0) ecotype. The position of these transitions is only weakly correlated with overall plant height, which undermines the common assumption that physically similar plants have closely matched growth profiles. * This kinematic profiling approach provides high-resolution growth phenotyping of the developing stem and thereby enables the harvest, pooling and analysis of developmentally matched tissue samples from multiple Arabidopsis plants. PMID- 22313382 TI - Silk-silica composites from genetically engineered chimeric proteins: materials properties correlate with silica condensation rate and colloidal stability of the proteins in aqueous solution. AB - The aim of the study was to determine the extent and mechanism of influence on silica condensation that is presented by a range of known silicifying recombinant chimeras (R5: SSKKSGSYSGSKGSKRRIL; A1: SGSKGSKRRIL; and Si4-1: MSPHPHPRHHHT and repeats thereof) attached at the N-terminus end of a 15-mer repeat of the 32 amino acid consensus sequence of the major ampullate dragline Spindroin 1 (Masp1) Nephila clavipes spider silk sequence ([SGRGGLGGQG AGAAAAAGGA GQGGYGGLGSQG](15)X). The influence of the silk/chimera ratio was explored through the adjustment of the type and number of silicifying domains (denoted X above), and the results were compared with their non-chimeric counterparts and the silk from Bombyx mori. The effect of pH (3-9) on reactivity was also explored. Optimum conditions for rate and control of silica deposition were determined, and the solution properties of the silks were explored to determine their mode(s) of action. For the silica-silk-chimera materials formed there is a relationship between the solution properties of the chimeric proteins (ability to carry charge), the pH of reaction, and the solid state materials that are generated. The region of colloidal instability correlates with the pH range observed for morphological control and coincides with the pH range for the highest silica condensation rates. With this information it should be possible to predict how chimeric or chemically modified proteins will affect structure and morphology of materials produced under controlled conditions and extend the range of composite materials for a wide spectrum of uses in the biomedical and technology fields. PMID- 22313383 TI - Reversible plasmonic circular dichroism of Au nanorod and DNA assemblies. AB - Reversible plasmonic circular dichroism (CD) responses are realized for the first time based on temperature-dependent assembly and disassembly of Au nanorod (Au NR) and DNA hybrids. Compared with the conventional UV-vis absorption spectra, the changes in both intensity and line shape of plasmonic CD signals are much more pronounced, leading to a preliminary detection limit of DNA as low as 75 nM. The mechanism and influence factors of reversible plasmonic CD responses are explored. PMID- 22313384 TI - Time- and temperature-dependent migration studies of Irganox 1076 from plastics into foods and food simulants. AB - The study provides an exhaustive set of migration data for octadecyl 3-(3,5-di tert-butyl-4-hydroxyphenyl)propionate (Irganox 1076) from low-density polyethylene (LDPE) in several food matrices. Irganox 1076 was used as a model migrant because it represents one of the typical substances used as an antioxidant in food packaging polymers. Kinetic (time-dependent) migration studies of Irganox 1076 were performed for selected foodstuffs chosen with different physical-chemical properties and in relation to the actual European food consumption market. The effect of fat content and of the temperature of storage on the migration from plastic packaging was evaluated. The results show that migration increased with fat content and storage temperature. All data obtained from real foods were also compared with data obtained from simulants tested in the same conditions. In all studied cases, the kinetics in simulants were higher than those in foodstuffs. The work provides data valuable for the extension of the validation of migration model developed on simulants to foodstuffs themselves. PMID- 22313385 TI - Investigation of nanostructure in room temperature ionic liquids using electronic excitation transfer. AB - Donor-donor electronic excitation transfer among 9-phenylanthracene (9PA) chromophores was measured in the room temperature ionic liquid (RTIL) 1-methyl-3 octylimidazolium chloride using time dependent fluorescence depolarization. 9PA, which is uncharged and nonpolar, will partition into the organic regions of the RTIL. The excitation transfer rate, which is sensitive to the distribution of chromophores in the RTIL, is modeled using different spatial configurations of 9PA molecules in the RTIL solution. The models are an isotropic distribution (random distribution) and a clustered sphere model to represent hydrophobic regions of a nanostructured environment. Model calculations were performed to demonstrate the sensitivity of excitation transfer to different distributions of chromophores. When compared to the experiment, the isotropic model can adequately match the data. From a Bayesian analysis of the sensitivity of the excitation transfer to the models for the spatial distribution of chromophores, an upper limit of 6 A radius is placed on the size of hydrophobic domains in the RTIL. PMID- 22313386 TI - Comparative efficacy of rHaa86 and rBm86 against Hyalomma anatolicum anatolicum and Rhipicephalus (Boophilus) microplus. AB - Hyalomma anatolicum anatolicum and Rhipicephalus (Boophilus) microplus are the most economically important tick species in India and other tropical and subtropical regions of the world and transmit pathogens causing animal and human diseases. We demonstrated that vaccination of animal by rHaa86 could be used for the control of both H. a. anatolicum and R. (B.) microplus infestations. By comparing the efficacy of rHaa86 and rBm86, it was observed that vaccine based on rHaa86 will be more effective in controlling homologous challenge infestations (68.7% against larvae and 45.8% against adults). The results of this trial demonstrated that species-specific antigens are the better choice for vaccine development and could serve as an effective tool for the integrated control of H. a. anatolicum. PMID- 22313387 TI - Bioremediation of industrial pharmaceutical drugs. AB - Recently, attention has been drawn toward the occurrence of pharmaceuticals in the environment. In recent years, many reports have been made on the occurrence of the large, differentiated group of pharmaceuticals in wastewater (PW), surface water, ground water, and in soil. The pharmaceutical sector is currently expanding in Tunisia, with more than 34 industries. The aim of this work was to evaluate the ability of Pseudomonas putida mt-2 to treat PW. P. putida was very efficient in reducing chemical oxygen demand (COD), total dissolved solids (TDS), and turbidity of solution (85.5, 89.1, and 81.5%, respectively). Genotoxicity of effluent, before and after biodegradation, was evaluated in vivo in mouse bone marrow by assessing the percentage of cells bearing different chromosome aberrations. Results indicated that PW showed a significant ability to induce DNA damage. In addition, PW induced a remarkable lipid peroxidation (LPO) effect, however, activities of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were unchanged when treated with PW, compared to nontreated PW. This toxicity was imputed to the presence of pharmaceutical compounds in wastewater. However, chromosome aberration, as well as LPO of PW, were significantly reduced after bioremediation. Thus, the use of this strain for testing on the industrial scale seems possible and advantageous. PMID- 22313388 TI - (-)-Epigallocatechin gallate induces Fas/CD95-mediated apoptosis through inhibiting constitutive and IL-6-induced JAK/STAT3 signaling in head and neck squamous cell carcinoma cells. AB - In this study, we examined the effects of several plant-derived natural compounds on head and neck squamous cell carcinoma (HNSCC) cells. The results revealed that (-)-epigallocatechin gallate (EGCG) demonstrated the most efficient cytotoxic effects on HNSCC cells. We then investigated the underlying molecular mechanism for the potent proapoptotic effect of EGCG on HNSCC. Cell apoptosis was observed in the EGCG-treated SAS and Cal-27 cells in a time- and dose-dependent manner. In concert with the caspase-8 activation by EGCG, an enhanced expression in functional Fas/CD95 was identified. Consistent with the increased Fas/CD95 expression, a drastic decrease in the Tyr705 phosphorylation of STAT3, a known negative regulator of Fas/CD95 transcription, was shown within 15 min in the EGCG treated cells, leading to downregulation of the target gene products of STAT3, such as bcl-2, vascular endothelial growth factor (VEGF), mcl-1, and cyclin D1. An overexpression in STAT3 led to resistance to EGCG, suggesting that STAT3 was a critical target of EGCG. Besides inhibiting constitutive expression, EGCG also abrogated the interleukin-6 (IL-6)-induced JAK/STAT3 signaling and further inhibited IL-6-induced proliferation on HNSCC cells. In comparison with apigenin, curcumin, and AG490, EGCG was a more effective inhibitor of IL-6-induced proliferation on HNSCC cells. Overall, our results strongly suggest that EGCG induces Fas/CD95-mediated apoptosis through inhibiting constitutive and IL-6 induced JAK/STAT3 signaling. This mechanism may be partially responsible for EGCG's ability to suppress proliferation of HNSCC cells. These findings provide that EGCG may be useful in the chemoprevention and/or treatment of HNSCC. PMID- 22313389 TI - Extremely bendable, high-performance integrated circuits using semiconducting carbon nanotube networks for digital, analog, and radio-frequency applications. AB - Solution-processed thin-films of semiconducting carbon nanotubes as the channel material for flexible electronics simultaneously offers high performance, low cost, and ambient stability, which significantly outruns the organic semiconductor materials. In this work, we report the use of semiconductor enriched carbon nanotubes for high-performance integrated circuits on mechanically flexible substrates for digital, analog and radio frequency applications. The as-obtained thin-film transistors (TFTs) exhibit highly uniform device performance with on-current and transconductance up to 15 MUA/MUm and 4 MUS/MUm. By performing capacitance-voltage measurements, the gate capacitance of the nanotube TFT is precisely extracted and the corresponding peak effective device mobility is evaluated to be around 50 cm(2)V(-1)s(-1). Using such devices, digital logic gates including inverters, NAND, and NOR gates with superior bending stability have been demonstrated. Moreover, radio frequency measurements show that cutoff frequency of 170 MHz can be achieved in devices with a relatively long channel length of 4 MUm, which is sufficient for certain wireless communication applications. This proof-of-concept demonstration indicates that our platform can serve as a foundation for scalable, low-cost, high-performance flexible electronics. PMID- 22313390 TI - Use of a video-ethnographic intervention (PRECESS Immersion Method) to improve skin-to-skin care and breastfeeding rates. AB - PURPOSES: Skin-to-skin care after birth often is absent, interrupted, or delayed for routine procedures. The purposes of this project were to improve skin-to-skin care and exclusive breastfeeding at hospital discharge. METHODS: For Part 1, we used a descriptive observational design, with video-ethnography and interaction analysis (PRECESS-Practice, Reflection, Education and training, Combined with Ethnography for Sustainable Success), during a 5-day quality improvement pilot study in a U.S. hospital (August 13-17, 2010). For Part 2, we used electronic health record review to test for differences in monthly rates of skin-to-skin care and exclusive breastmilk feeding (baseline, July 2010; post-intervention, August-December 2010). RESULTS: In Part 1, 11 mothers and babies participated: 10 (91%) received immediate skin-to-skin care, eight (73%) received uninterrupted skin-to-skin care, nine (82%) planned to breastfeed, six (67%) of these babies were exclusively breastfeeding at hospital discharge, and five (83%) of the six babies who completed all nine instinctive stages during skin-to-skin care were exclusively breastfeeding at hospital discharge. In our subsequent review (Part 2), we found a significant improvement (25% above baseline) in the overall rate of skin-to-skin care across post-intervention months (Pearson chi(2)=23.798, df=5, p<0.000), predominantly from improvements in the cesarean section population. The rates of exclusive breastfeeding showed no significant change. CONCLUSIONS: The PRECESS immersion method may help to rapidly improve skin-to skin care. Babies who undergo all nine stages during skin-to-skin care may be more likely to exclusively breastfeed. Mothers need support during skin-to-skin care to recognize their baby's readiness to breastfeed. Skin-to-skin care during cesarean surgery may reduce maternal stress and improve satisfaction with the surgical experience. PMID- 22313391 TI - Influence of common birth interventions on maternal blood pressure patterns during breastfeeding 2 days after birth. AB - OBJECTIVE: This study investigated possible influences of medical interventions during labor on maternal blood pressure during a breastfeed 2 days postpartum. SUBJECTS AND METHODS: Sixty-six primiparae with normal deliveries were consecutively recruited. Blood pressure was measured at -5, 10, 30, and 60 minutes during a morning breastfeed 2 days postpartum. Five treatment groups were formed based on the medical interventions received during labor: Non-medicated mothers (Control group, n=21); mothers receiving epidural analgesia (EDA) with oxytocin (OT) stimulation (EDA(OT) group, n=14); mothers receiving EDA without OT stimulation (EDA(non-OT) group, n=7); mothers receiving OT stimulation only (OT intravenously [iv] group, n=9); and mothers receiving 10 IU of OT intramuscularly (im) only (OT im group, n=15). RESULTS: Baseline diastolic, but not systolic, blood pressure differed between the groups as displayed by significantly lower diastolic blood pressure in the EDA(non-OT) group compared with the Control group, the OT iv group, and the EDA(OT) group (p=0.045, p=0.041, and p=0.024, respectively). Both systolic and diastolic blood pressure fell significantly during the breastfeeding session in the Control group (p=0.001 and p=0.004, respectively), the OT im group (p=0.006 and p=0.001, respectively), and the EDA(OT) group (p=0.028 and p=0.002, respectively), and the fall in diastolic blood pressure tended to be significant in the OT iv group (p=0.050). The duration of skin-to-skin contact before breastfeeding correlated positively with the decrease in systolic blood pressure in the OT im group (R(s)=0.540, p=0.046). CONCLUSION: Administration of EDA during labor lowers baseline diastolic blood pressure and abolishes the fall in blood pressure in response to a breastfeed 2 days after birth. PMID- 22313392 TI - Maternal smoking does not influence vitamin A and E concentrations in mature breastmilk. AB - OBJECTIVES: The aim of this study was to analyze the effects of maternal smoking on the total antioxidant status (TAS) and the concentrations of vitamins A and E in human breastmilk. METHODOLOGY: The study group (n=20) comprised postpartum women who declared smoking more than five cigarettes per day (confirmed by urinalysis of the cotinine concentration). The control group included 25 nonsmoking postpartum women. Breastmilk samples were collected between day 30 and day 32 after delivery. TAS was determined by Rice-Evans and Miller method, whereas the amount of vitamins A and E was measured by high-performance liquid chromatography. RESULTS: No significant differences were observed between breastmilk samples from smoking and nonsmoking mothers in terms of TAS and vitamin A and E concentrations. Additionally, no significant correlations were found between urinary cotinine and TAS (R=0.35, p=0.144) or vitamin A (R=0.14, p=0.571) and vitamin E (R=0.31, p=0.228) concentrations in breastmilk samples from smoking mothers. CONCLUSIONS: Maternal smoking is not reflected by decreased TAS and vitamin A and E concentrations in mature milk. PMID- 22313393 TI - Does the LATCH score assessed in the first 24 hours after delivery predict non exclusive breastfeeding at hospital discharge? AB - AIM: The aims of this study were to analyze the relationship between the LATCH score assessed in the first 24 hours after delivery and non-exclusive breastfeeding at discharge and to identify a cutoff for the LATCH score in order to identify women with higher risk of non-exclusive breastfeeding who may need additional breastfeeding support. SUBJECTS AND METHODS: We conducted a prospective observational study in the Maternity Ward of the Institute for Maternal and Child Health "Burlo Garofolo" (Trieste, Italy) and collected data from 299 mother-infant dyads. RESULTS: The rate of nonexclusive breastfeeding was inversely related to the LATCH score (p<0.001) with non-exclusive breastfeeding infants scoring less (6.9) than infants exclusively breastfed at discharge (7.6) (p=0.001). In multivariate analysis, non-exclusive breastfeeding was also associated with cesarean section, primiparity, and infant phototherapy. In order to support maternity staff in providing targeted interventions, we identified four LATCH score cutoffs associated with as many risk groups for non-exclusive breastfeeding at discharge. CONCLUSIONS: The LATCH score is a useful tool to identify mother-infant pairs who might benefit from additional skilled support in specific subgroups at risk of non-exclusive breastfeeding at discharge. Future research is needed to explore if the LATCH score assessed in the first days of life can also predict the duration of breastfeeding. PMID- 22313394 TI - Human erythrocyte remodelling during Plasmodium falciparum malaria parasite growth and egress. AB - The intra-erythrocyte growth and survival of the malarial parasite Plasmodium falciparum is responsible for both uncomplicated and severe malaria cases and depends on the parasite's ability to remodel its host cell. Host cell remodelling has several functions for the parasite, such as acquiring nutrients from the extracellular milieu because of the loss of membrane transporters upon erythrocyte differentiation, avoiding splenic clearance by conferring cytoadhesive properties to the infected erythrocyte, escaping the host immune response by exporting antigenically variant proteins at the red blood cell surface. In addition, parasite-induced changes at the red blood cell membrane and sub-membrane skeleton are also necessary for the efficient release of the parasite progeny from the host cell. Here we review these cellular and molecular changes, which might not only sustain parasite growth but also prepare, at a very early stage, the last step of egress from the host cell. PMID- 22313395 TI - Pulmonary venous stenosis in a premature infant with bronchopulmonary dysplasia: clinical and autopsy findings of these newly associated entities. AB - Pulmonary venous stenosis is rare and is most commonly found in association with cardiac malformations. Recent studies have associated pulmonary venous stenosis with prematurity, especially with bronchopulmonary dysplasia, although no such case has been documented at autopsy. We report the case of a 26-week-gestation infant who required ventilation at birth and who, among other complications, developed chronic lung disease of prematurity by the age of 3 months. Imaging showed suprasystemic right-sided pressures and pulmonary venous stenosis. Despite aggressive management of respiratory status and surgical marsupialization of stenoses, the infant expired after 3 weeks. At autopsy, 3 of 4 pulmonary veins showed a fibrous ridge obstructing atrial ostia with otherwise normal anatomy. The lungs showed bronchopulmonary dysplasia, pulmonary hypertensive vascular changes, and features of venous obstruction. Pulmonary venous stenosis and bronchopulmonary dysplasia in premature infants may be pathogenetically related. Coincidence of these diseases is likely underrecognized, and careful cardiac examination in these patients is warranted. PMID- 22313396 TI - P53 and its molecular basis to chemoresistance in breast cancer. AB - INTRODUCTION: TP53 mutations have been associated with resistance to anthracyclines and mitomycin in breast cancer. This review examines the potential roles of different components in the p53 cascade with respect to drug resistance. AREAS COVERED: Literature was searched using the ISI Web and Pubmed. Considering p53 activation in response to genotoxic stress and phosphorylations by ataxia telangiectasia mutated/ataxia telangiectasia and radiation resistance gene 3 related (ATM/ATR). Downstream checkpoint proteins chk1 and chk2 are also considered to be of major importance. Recently, nonsense mutations in CHEK2, encoding the chk2 protein, were found to predict resistance to anthracycline therapy in some tumours harbouring wild-type TP53. While mouse double minute (MDM)2 or MDMX protein overexpression (often due to gene amplifications) may inactivate p53 in different tumour forms, so far, there is no evidence for MDM2 amplifications in breast cancers resistant to anthracyclines. The roles of p53 isoforms and p53-induced transcription of non-coding RNA remain to be defined. EXPERT OPINION: Disturbances affecting the 'p53 pathway(s)' may play a key role in chemoresistance in cancer. Although TP53 is not a clinical marker for drug resistance, like other genes (such as breast cancer associated 1/2 (BRCA1/2)) it may be considered a 'beacon' identifying critical gene cascades. PMID- 22313397 TI - Phosphasalen yttrium complexes: highly active and stereoselective initiators for lactide polymerization. AB - Preparation and characterization of three yttrium alkoxide complexes with new phosphasalen ligands are reported. The phosphasalens are analogues of the well known salen ligands but with iminophosphorane donors replacing the imine functionality. The three yttrium alkoxide complexes show mono- and dinuclear structures in the solid state, depending on the substituents on the ligand. The new ligands and complexes are characterized using multinuclear NMR spectroscopy, mass spectrometry, elemental analysis, and single-crystal X-ray diffraction experiments. The complexes are all rapid initiators for lactide polymerization; they show excellent polymerization control on addition of exogeneous alcohol. The mononuclear complex shows extremely rapid rates and a high degree of stereocontrol in rac-lactide polymerization, yielding heterotactic PLA (P(s) of 0.9). The phosphasalens are, therefore, excellent ligands for lactide ring opening polymerization catalysis showing superior rates and stereocontrol versus salen ligands, which may be related to their excellent donating ability and the high degrees of steric protection they can confer. PMID- 22313398 TI - Modular design of micropattern geometry achieves combinatorial enhancements in cell motility. AB - Basic micropattern shapes, such as stripes and teardrops, affect individual facets of cell motility, such as migration speed and directional bias, respectively. Here, we test the idea that these individual effects on cell motility can be brought together to achieve multidimensional improvements in cell behavior through the modular reconstruction of the simpler "building block" micropatterns. While a modular design strategy is conceptually appealing, current evidence suggests that combining environmental cues, especially molecular cues, such as growth factors and matrix proteins, elicits a highly nonlinear, synergistic cell response. Here, we show that, unlike molecular cues, combining stripe and teardrop geometric cues into a hybrid, spear-shaped micropattern yields combinatorial benefits in cell speed, persistence, and directional bias. Furthermore, cell migration speed and persistence are enhanced in a predictable, additive manner on the modular spear-shaped design. Meanwhile, the spear micropattern also improved the directional bias of cell movement compared to the standard teardrop geometry, revealing that combining geometric features can also lead to unexpected synergistic effects in certain aspects of cell motility. Our findings demonstrate that the modular design of hybrid micropatterns from simpler building block shapes achieves combinatorial improvements in cell motility. These findings have implications for engineering biomaterials that effectively mix and match micropatterns to modulate and direct cell motility in applications, such as tissue engineering and lab-on-a-chip devices. PMID- 22313399 TI - Cloning splice variants. PMID- 22313400 TI - Sequencing's next big gamble. PMID- 22313403 TI - Profile of Susan Gottesman. PMID- 22313404 TI - Genomics moves into the clinic. PMID- 22313405 TI - [Letter to the editor] Combined FAM-labeled TaqMan probe detection and SYBR green I melting curve analysis in multiprobe qPCR genotyping assays. PMID- 22313406 TI - Length and GC-biases during sequencing library amplification: a comparison of various polymerase-buffer systems with ancient and modern DNA sequencing libraries. AB - High-throughput sequencing technologies frequently necessitate the use of PCR for sequencing library amplification. PCR is a sometimes enigmatic process and is known to introduce biases. Here we perform a simple amplification-sequencing assay using 10 commercially available polymerase-buffer systems to amplify libraries prepared from both modern and ancient DNA. We compare the performance of the polymerases with respect to a previously uncharacterized template length bias, as well as GC-content bias, and find that simply avoiding certain polymerase can dramatically decrease the occurrence of both. For amplification of ancient DNA, we found that some commonly used polymerases strongly bias against amplification of endogenous DNA in favor of GC-rich microbial contamination, in our case reducing the fraction of endogenous sequences to almost half. PMID- 22313407 TI - Increased affinity and solubility of peptides used for direct peptide ELISA on polystyrene surfaces through fusion with a polystyrene-binding peptide tag. AB - Peptide reagents can serve as alternatives or replacements to antibodies in sensing or diagnostic applications. The passive adsorption of peptides onto polystyrene surfaces can limit the target binding capability, especially for short, positively charged, or hydrophobic sequences. In this report, we show that fusing a peptide with a previously characterized 12-amino acid polystyrene binding sequence (PS-tag) improves overall peptide solubility and enzyme-linked immunosorbent assay (ELISA) results using the peptide as a capture agent. Specific improvements for protective antigen (PA; Bacillus anthracis) protein binding peptides selected from bacterial surface display were compared with native or biotinylated peptides. The PS-tag was added to either peptide terminus, using a (Gly)(4) spacer, and comparable binding affinities were obtained. Fusion with the PS-tag did not have any negative impact on peptide secondary structure as measured by circular dichroism. The addition of the PS-tag provides a convenient method to utilize peptide reagents from peptide display libraries as capture agents in an ELISA format without the need for a biotin tag or concerns about passive adsorption of critical residues for target capture. PMID- 22313408 TI - Detection of SNARE complexes with FRET using the tetracysteine system. AB - The three proteins synaptosomal-associated protein 25 (SNAP-25), Syntaxin-1a and vesicle-associated membrane protein (VAMP-2) are collectively called SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors). By assembling into an exocytic complex, the three SNAREs help in catalyzing membrane fusion. Due to lack of probes that adequately reconstitute the intracellular behavior of endogenous SNAREs, the dynamics of SNARE complexes in living cells is poorly understood. Here we describe a new FRET-based probe, called Cerulean-SNAP 25-C4 (CSNAC), that can track the conformational changes undergone by SNAP-25 as exocytic complexes assemble. The fluorescent protein Cerulean was attached to the N terminus and served as a FRET donor. The biarsenical dye FlAsH served as a FRET acceptor and was attached to a short tetracysteine motif (C4) motif inserted into the so-called linker domain of SNAP-25. CSNAC reported successive FRET changes when first Syntaxin-1a and then VAMP-2 were added in vitro. Small tetracysteine insertions used as a FRET acceptor are expected to have less steric hindrance than previously used GFP-based fluorophores. We propose that genetically-encoded tetracysteine tags can be used to study regulated SNARE complex assembly in vivo. PMID- 22313409 TI - Global analysis of RNA oxidation in Saccharomyces cerevisiae. AB - Oxidative RNA damage has been linked to loss of RNA function and to the development of many human age-related diseases. Consequently, a need exists for methods to identify and quantify the extent of RNA oxidation on a genome-wide basis. We developed such a method by combining affinity selection of mRNA containing 8-hydroxyguanine with high throughput DNA sequencing. We demonstrate that this assay is suitable for detecting differences in the extent of oxidation between RNA transcripts. We applied this method to the yeast Saccharomyces cerevisiae grown under physiological conditions and in response to hydrogen peroxide, and detected significantly oxidized RNA transcripts. PMID- 22313410 TI - Dynamics of singlet oxygen generation by DNA-binding photosensitizers. AB - The dynamics of photosensitized singlet oxygen generation in a DNA microenvironment were examined using the DNA-binding photosensitizers berberine and palmatine. These photosensitizers generate singlet oxygen only under interaction with DNA because the singlet excited state deactivates rapidly in a nonbinding environment. A kinetic study demonstrated the reaction process whereby singlet oxygen is generated through energy transfer from the triplet excited state of DNA-binding berberine (or palmatine) to molecular oxygen. The guanine containing sequence of DNA slightly deactivated the singlet excited state of the photosensitizers, resulting in a decrease of the singlet oxygen yield. By the steric hindrance of the DNA strand, the rate constant of the singlet oxygen generation became smaller than that of the other water-soluble photosensitizer. PMID- 22313411 TI - Radioiodine treatment of metastatic thyroid cancer: relative efficacy and side effect profile of preparation by thyroid hormone withdrawal versus recombinant human thyrotropin. AB - BACKGROUND: To effectively treat differentiated thyroid cancer (DTC) with radioiodine (RAI) it is necessary to raise serum thyrotropin (TSH) levels either endogenously by thyroid hormone withdrawal (THW) or exogenously by administration of recombinant human TSH (rhTSH). The aim of our study was to compare the relative efficacy and side effect profile of rhTSH versus THW preparation for RAI therapy of metastatic DTC. METHODS: Fifty-six patients (31 women and 25 men) with RAI-avid distant metastases of DTC treated with either rhTSH-aided (n=15) or THW aided RAI (n=41) and followed for 72+/-36.2 months were retrospectively analyzed. The groups were comparable in regard to mean size of target lesions (rhTSH vs. THW 6.4 vs. 4.8 cm, p=0.41), mean baseline thyroglobulin level (6995 vs. 5544 ng/mL, p=0.83), distribution of micronodular and macronodular pulmonary metastases (67% vs. 63%, p=0.54, 13% vs. 15% p=0.64, respectively), osseous (53% vs. 29%, p=0.09), brain (0% vs. 2%, p=0.73), and liver/kidney metastases (13% vs. 2%, p=0.61). Patients in the rhTSH group were older (rhTSH vs. THW mean 62 vs. 49 years, p=0.01), and received lower cumulative RAI dose (256 vs. 416 mCi, p=0.03), which was more frequently based on dosimetric calculations (80% vs. 46%, p=0.024). Responses to treatment were based on RECIST 1.1 criteria. RESULTS: Adjusted by age rates of complete response (CR), stable disease (SD), progressive disease (PD), and progression free survival (PFS) were not different between the groups (rhTSH vs. THW CR hazard ratio [HR] 0.97, 95% CI 0.08-11.42, p=0.982; SD HR 3.22, 95% CI 0.79-13.18, p=0.104, PD HR 0.26, 95% CI 0.52-1.26, p=0.094; PFS HR 0.41, 95% CI 0.14-1.23, p=0.112). The only independent risk factor for nonresponding to treatment and presentation with PD was age (HR 1.06, 95% CI 1.02 1.11, p=0.008). Age was also an independent factor affecting PFS (HR 1.04 for each year, 95% CI 1.02-1.07, p=0.001). Rates of leukopenia, thrombocytopenia, xerostomia, and restrictive pulmonary disease after RAI were not significantly different (rhTSH vs. THW 30% vs. 28%, p=0.61, 10% vs. 0%, p=0.37, 0% vs. 12%, p=0.20, 0% vs. 2%, p=0.73, respectively). CONCLUSIONS: Patients with metastatic DTC prepared with rhTSH achieve comparable benefit of RAI therapy as those treated after THW. PMID- 22313412 TI - Metastases to the thyroid: a review of the literature from the last decade. AB - BACKGROUND: Although clinically evident metastases of nonthyroid malignancies (NTMs) to the thyroid gland are uncommon, it is important to suspect them in patients who present with a new thyroid mass and a history, however far back, of prior malignancy. In fact, metastases from NTMs to the thyroid gland have been reported in 1.4%-3% of all patients who have surgery for suspected cancer in the thyroid gland. Here we review the literature over the last decade regarding this topic. SUMMARY: Based on recent literature, the most common NTMs that metastasize to the thyroid gland are renal cell (48.1%), colorectal (10.4%), lung (8.3%), and breast carcinoma (7.8%), and sarcoma (4.0%). Metastases of NTMs to the thyroid are more common in women than men (female to male ratio=1.4 to 1) and in nodular thyroid glands (44.2%). The mean and median intervals between diagnosing NTMs and their metastases to thyroid gland are 69.9 and 53 months, respectively. In 20% of cases the diagnosis of the NTM and its metastases to the thyroid was synchronous. Recent reports indicate that there is a higher frequency of sarcoma metastasizing to the thyroid gland than reported in prior years. Fine-needle aspiration biopsy (FNAB) of thyroid masses is useful in diagnosis of thyroid metastases. However, this requires information about the NTM so that the proper antibodies can be used for immunohistochemical analysis; therefore it is of lesser utility if the NTM is occult. In patients with preexisting thyroid pathology the FNAB diagnosis can be more difficult due to more than one lesion being present. CONCLUSIONS: It is important to keep in mind that the thyroid gland can be a site of metastases for a variety of tumors when evaluating a thyroid nodule, especially in a patient with a prior history of malignancy. In patients with thyroid lesions and a history of malignant disease, regardless of time elapsed since the initial diagnosis of the primary neoplasm, disease recurrence or progression of malignancy must be considered until proven otherwise. PMID- 22313413 TI - Caffeine treatment disturbs the angiogenesis of zebrafish embryos. AB - Caffeine is a widely consumed substance that occurs in numerous dietary sources, but teratogenic effects of caffeine intake during embryonic development are still not clear. In the present study, we used the zebrafish as a model to assess caffeine-induced toxicity on embryonic vascular development. A green fluorescent vascular endothelium transgenic line, Tg(fli1:egfp), was utilized for the sensitive detection of vascular development, including vasculo- and angiogenesis. Caffeine-treated embryos showed no defects in vasculogenesis, but revealed dose dependent (250-350 ppm) developmental defects in intersegmental vessels, dorsal longitudinal anastomotic vessels, and subintestinal vein sprouting. Further, real time polymerase chain reaction analysis of caffeine-treated embryos showed an upregulation of nrp1a along with a downregulation of sema3aa and sema3c. In conclusion, caffeine treatment induces defects of angiogenesis in zebrafish embryos. PMID- 22313414 TI - Multiple and reversible hydrogenases for hydrogen production by Escherichia coli: dependence on fermentation substrate, pH and the F(0)F(1)-ATPase. AB - Molecular hydrogen (H(2)) can be produced via hydrogenases during mixed-acid fermentation by bacteria. Escherichia coli possesses multiple (four) hydrogenases. Hydrogenase 3 (Hyd-3) and probably 4 (Hyd-4) with formate dehydrogenase H (Fdh-H) form two different H(2)-evolving formate hydrogen lyase (FHL) pathways during glucose fermentation. For both FHL forms, the hycB gene coding small subunit of Hyd-3 is required. Formation and activity of FHL also depends on the external pH ([pH](out)) and the presence of formate. FHL is related with the F(0)F(1)-ATPase by supplying reducing equivalents and depending on proton-motive force. Two other hydrogenases, 1 (Hyd-1) and 2 (Hyd-2), are H(2) oxidizing enzymes during glucose fermentation at neutral and low [pH](out). They operate in a reverse, H(2)-producing mode during glycerol fermentation at neutral [pH](out). Hyd-1 and Hyd-2 activity depends on F(0)F(1). Moreover, Hyd-3 can also work in a reverse mode. Therefore, the operation direction and activity of all Hyd enzymes might determine H(2) production; some metabolic cross-talk between Hyd enzymes is proposed. Manipulating of different Hyd enzymes activity is an effective way to enhance H(2) production by bacteria in biotechnology. Moreover, a novel approach would be the use of glycerol as feedstock in fermentation processes leading to H(2) production, reduced fuels and other chemicals with higher yields than those obtained by common sugars. PMID- 22313415 TI - Phylogenetic position of the adeleorinid coccidia (Myzozoa, Apicomplexa, Coccidia, Eucoccidiorida, Adeleorina) inferred using 18S rDNA sequences. AB - Investigating the evolutionary relationships of the major groups of Apicomplexa remains an important area of study. Morphological features and host-parasite relationships continue to be important in the systematics of the adeleorinid coccidia (suborder Adeleorina), but the systematics of these parasites have not been well-supported or have been constrained by data that were lacking or difficult to interpret. Previous phylogenetic studies of the Adeleorina have been based on morphological and developmental characters of several well-described species or based on nuclear 18S ribosomal DNA (rDNA) sequences from taxa of limited taxonomic diversity. Twelve new 18S rDNA sequences from adeleorinid coccidia were combined with published sequences to study the molecular phylogeny of taxa within the Adeleorina and to investigate the evolutionary relationships of adeleorinid parasites within the Apicomplexa. Three phylogenetic methods supported strongly that the suborder Adeleorina formed a monophyletic clade within the Apicomplexa. Most widely recognized families within the Adeleorina were hypothesized to be monophyletic in all analyses, although the single Hemolivia species included in the analyses was the sister taxon to a Hepatozoon sp. within a larger clade that contained all other Hepatozoon spp. making the family Hepatozoidae paraphyletic. There was an apparent relationship between the various clades generated by the analyses and the definitive (invertebrate) host parasitized and, to lesser extent, the type of intermediate (vertebrate) host exploited by the adeleorinid parasites. We conclude that additional taxon sampling and use of other genetic markers apart from 18S rDNA will be required to better resolve relationships among these parasites. PMID- 22313416 TI - Me3(OMe)tBuXPhos: a surrogate ligand for Me4tBuXPhos in palladium-catalyzed C-N and C-O bond-forming reactions. AB - A new biarylphosphine ligand, Me(3)(OMe)tBuXPhos (L3), was designed as a surrogate for Me(4)tBuXPhos (L1). The Me(3)(OMe)tBuXPhos could be prepared in a chromatography-free manner from inexpensive and readily available 2,3,6 trimethylphenol. Comparative studies demonstrated that a catalyst based on Me(3)(OMe)tBuXPhos displayed the same reactivity as a catalyst based on Me(4)tBuXPhos for Pd-catalyzed C-N and C-O bond-forming processes. PMID- 22313417 TI - Antiproliferative effects of a new alpha-lipoic acid derivative, DHL-HisZnNa, in HT29 human colon cancer cells in vitro. AB - OBJECTIVE: alpha-Lipoic acid has been reported to induce apoptosis in several cancer cell lines. However, it is prone to oxidation, polymerization and desulfurization, and is insoluble in water. In this study an alpha-lipoic acid derivative, sodium N-(dihydrolipoyl)-l-histidinate zinc complex (DHL-HisZnNa), was synthesized, which can eliminate active oxygen species. The antiproliferative effects of DHL-HisZnNa, on human colon cancer cell HT29 in vitro, were evaluated. METHODS: Whether DHL-HisZnNa elicits its antiproliferative effects by inducing apoptosis and cell cycle arrest, was investigated. Expressions of cell-cycle related proteins and their phosphorylation on HT-29 was also analyzed. RESULTS: DHL-HisZnNa inhibited cancer cell growth in cultures. Cell cycle analysis by flow cytometry showed time-dependent accumulation of HT-29 cells in G1 phase after exposure to DHL-HisZnNa. Analysis of DNA fragmentation did not reveal evidence of apoptosis after exposure to DHL-HisZnNa. Cells treated with DHL-HisZnNa showed an increase in p53 phosphorylation with the Bio-Plex Phosphoprotein assay. DHL HisZnNa increased protein levels of the cyclin-dependent kinase inhibitor p21 and decreased that of phosphorylated retinoblastoma protein (Rb) by western blot analysis. Results obtained with DHL-HisZnNa are on a single colon cancer cell line and not comparative experiments with alpha-lipoic acid. CONCLUSIONS: This is the first study, to our knowledge, to report the antiproliferative effects of DHL HisZnNa and the molecular mechanisms by which it inhibits growth of HT29. PMID- 22313419 TI - When and why does abuse predict reduced autobiographical memory specificity? AB - Two studies were conducted to explore the conditions that elicit autobiographical memory problems in abuse victims and the mechanism that underlie them. In Study 1 older adolescents (n=80) with and without self-reported abuse histories completed a modified version of the Autobiographical Memory Test (AMT-U); participants were given an unlimited amount of time to provide specific memories in response to cue words. Participants also completed measures of depression and post-traumatic stress disorder (PTSD), working memory, and attentional biases. This study found that abuse severity and PTSD symptoms were positively related to memory specificity on the AMT-U. In Study 2 older adolescents (n=78) with and without self-reported abuse histories completed the traditional (timed) version of the AMT. Participants also completed measures of working memory, attentional biases, self-reported coping, and psychopathological symptoms (i.e., depression and PTSD). In this study the opposite relationship was observed, such that abuse severity was related to poorer memory specificity, but this relationship was explained by disengagement coping and PTSD symptoms. This work suggests that poor memory specificity may represent a form of avoidance, but the application of avoidant mechanisms depends on the remembering context. PMID- 22313420 TI - Type or dimension? A taxometric investigation of flashbulb memories. AB - Flashbulb memories (FBMs) have been defined as vivid and detailed memory of a reception context under which one first heard of a public and unexpected emotional event. One of the issues still open for research on FBMs is to understand whether this latent construct has to be conceptualised as a continuum with other autobiographical memories, or whether it represents a special cluster of memories. This theoretical distinction has some implications for the measurement of the phenomenon, that could be assessed by a dimensional or categorical (taxonic) model. The current study attempted to provide an empirical answer to the problem of FBM measurement, by adopting a taxometric analysis. The main strength of these analyses is to treat taxonic and dimensional models as two competing hypotheses and to evaluate the relative support for each of them. Taxometric analyses were applied to FBM data for the Pope's death, and results supported the taxonic structure of FBMs. PMID- 22313421 TI - "The people I grew up with": the role of sociodemographic factors in early memories in an Italian sample. AB - This within-culture study aimed to investigate the age and density of earliest memories in a sample of Italian young adults. The framework of this study is sociocultural, with an emphasis on family reminiscing as contributing to early memories. In this regard Italy is of interest due to the fact that it is a Western but familial oriented culture, where multi-generational family ties are still strong in comparison with other European counterparts, providing for the opportunity to investigate the offset of childhood amnesia as a function of growing up in an extended family structure. Consistent with Mullen (1994), 90 undergraduate students were interviewed about their earliest memory and about sociodemographic factors in their early childhood years: household composition, gender, birth order, presence of family moves, and significant early childhood experiences. Participants who grew up in an extended family situation reported earlier and denser memories in comparison with those from nuclear families. Results are discussed in light of other cross-cultural work on childhood amnesia and with respect to sociocultural theories of the importance of family reminiscing for one's early memories. PMID- 22313422 TI - Genetic analysis of the CYP21A2 gene in neonatal dried blood spots from children with transiently elevated 17-hydroxyprogesterone. AB - BACKGROUND: Neonatal screening for congenital adrenal hyperplasia (CAH) identifies a certain proportion of newborns with transient moderate elevation of 17-hydroxyprogesterone (17-OHP). These children require regular follow-up until normalization of their 17-OHP levels. We investigated the possibility of reducing the individuals' recall rates by using genetic methods on their original neonatal dried blood spots. PATIENTS AND METHODS: We analysed neonatal dried blood spots from 753 subjects with transiently elevated levels of 17-OHP. The CYP21A2 gene was sequenced to detect point mutations, and the presence of CYP21A2 was further confirmed by two methods utilizing the difference between CYP21A2 and its CYP21A1P pseudogene in the sequence of exon 3 (8-bp deletion). The accuracy of the methods was verified using samples from 70 subjects with known CYP21A2 mutations and 181 healthy children. RESULT: Among the 701 successfully sequenced samples from subjects with transiently elevated 17-OHP, 670 (95%) had no point mutations or novel variants in the CYP21A2 gene. We found no individuals carrying genotypes consistent with the diagnosis of CAH (i.e. homozygotes or compound heterozygotes for point mutations, large deletions or rearrangements). However, 21 heterozygous carriers of known point mutations that cause the classic and nonclassic forms of CAH were identified. Additionally, we detected eight heterozygous and two homozygous point variants with unknown functional significance. CONCLUSION: Although CAH caused by 21-hydroxylase deficiency could be genetically excluded with a reasonable degree of confidence in 95% of the genotyped subjects that had transiently elevated 17-OHP, the performance of the tests was suboptimal when performed using dried blood spots and time-consuming in comparison with the current practice of repeated measurements of 17-OHP. The introduction of this method into clinical practice seems to be impractical at this stage. PMID- 22313423 TI - Effect of bond rigidity and molecular structure on the self-assembly of amphiphilic molecules using second-order classical density functional theory. AB - Second-order classical density functional theory is applied to assess the effect of surfactant properties on the interfacial structure and interfacial tension of a planar oil/water interface. Specifically the affect of the relative locations of the hydrophobic and hydrophilic portions, rigidity vs flexibility, and bond angle of the surfactant are investigated. It is found that bond angle and branching significantly affect the tendency of a surfactant to adsorb on the interface and the degree to which the interfacial tension is lowered. PMID- 22313424 TI - Insight into serum protein interactions with functionalized magnetic nanoparticles in biological media. AB - Surface modification with linear polymethacrylic acid (20 kDa), linear and branched polyethylenimine (25 kDa), and branched oligoethylenimine (800 Da) is commonly used to improve the function of magnetite nanoparticles (MNPs) in many biomedical applications. These polymers were shown herein to have different adsorption capacity and anticipated conformations on the surface of MNPs due to differences in their functional groups, architectures, and molecular weight. This in turn affects the interaction of MNPs surfaces with biological serum proteins (fetal bovine serum). MNPs coated with 25 kDa branched polyethylenimine were found to attract the highest amount of serum protein while MNPs coated with 20 kDa linear polymethacrylic acid adsorbed the least. The type and amount of protein adsorbed, and the surface conformation of the polymer was shown to affect the size stability of the MNPs in a model biological media (RPMI-1640). A moderate reduction in r(2) relaxivity was also observed for MNPs suspended in RPMI-1640 containing serum protein compared to the same particles suspended in water. However, the relaxivities following protein adsorption are still relatively high making the use of these polymer-coated MNPs as Magnetic Resonance Imaging (MRI) contrast agents feasible. This work shows that through judicious selection of functionalization polymers and elucidation of the factors governing the stabilization mechanism, the design of nanoparticles for applications in biologically relevant conditions can be improved. PMID- 22313425 TI - Confirmation of K-momentum dark exciton vibronic sidebands using 13C-labeled, highly enriched (6,5) single-walled carbon nanotubes. AB - A detailed knowledge of the manifold of both bright and dark excitons in single walled carbon nanotubes (SWCNTs) is critical to understanding radiative and nonradiative recombination processes. Exciton-phonon coupling opens up additional absorption and emission channels, some of which may "brighten" the sidebands of optically forbidden (dark) excitonic transitions in optical spectra. In this report, we compare (12)C and (13)C-labeled SWCNTs that are highly enriched in the (6,5) species to identify both absorptive and emissive vibronic transitions. We find two vibronic sidebands near the bright (1)E(11) singlet exciton, one absorptive sideband ~200 meV above, and one emissive sideband ~140 meV below, the bright singlet exciton. Both sidebands demonstrate a ~50 cm(-1) isotope-induced shift, which is commensurate with exciton-phonon coupling involving phonons of A[Formula: see text] symmetry (D band, omega ~ 1330 cm(-1)). Independent analysis of each sideband indicates that both sidebands arise from the same dark exciton level, which lies at an energy approximately 25 meV above the bright singlet exciton. Our observations support the recent prediction of, and mounting experimental evidence for, the dark K-momentum singlet exciton lying ~25 meV (for the (6,5) SWCNT) above the bright Gamma-momentum singlet. This study represents the first use of (13)C-labeled SWCNTs highly enriched in a single nanotube species to unequivocally confirm these sidebands as vibronic sidebands of the dark K-momentum singlet exciton. PMID- 22313426 TI - Consecutive mutational events in a TSHR allele of Arab families with resistance to thyroid stimulating hormone. AB - BACKGROUND: Our laboratory identified six distinct inactivating TSHR gene mutations in Arab tribes living in Israel. We recently reported three nucleotide substitutions in exon 3 producing p.[L89L;Q90P] and one in exon 9 of the same allele producing p.P264S in Family A. Family B, reported herein, harbors the identical mutation in exon 3 only. We set to determine whether the mutations have common ancestral origin. METHODS: Coding regions of the TSHR were sequenced and flanking microsatellite markers spanning 5.3 cM were used for haplotyping. RESULTS: Two siblings of Family B were compound heterozygous for TSHR gene mutations. The paternal allele contained the exon 3 mutation and the maternal allele harbored a mutation in exon 10 (p.L653V). We investigated the possibility of a founder effect with subsequent mutational events for the presence of the same exon 3 mutation in different families. The haplotype of the allele harboring the exon 3 mutation in Family B was identical to that of Family A, also harboring the exon 9 mutation on the same allele, indicating that the latter occurred subsequently. The ancestral wild-type TSHR was present in Family B, suggesting that the mutation in exon 3 was also new in the history of that population. CONCLUSIONS: It is more likely that two consecutive mutational events occurred on the ancestral wild-type allele instead of a recombination bringing exon 3 and exon 9 mutations together on the same allele. New mutational events contribute to the high prevalence of TSHR mutations in this population in addition to a founder effect and limited gene pool due to inbreeding. PMID- 22313427 TI - Propylthiouracil-induced interstitial pneumonia in a Caucasian woman with amiodarone-induced thyrotoxicosis. AB - BACKGROUND: Propylthiouracil (PTU) therapy is associated with a variety of adverse reactions, among the most rare being interstitial pneumonia. To date, this has been reported in four Asian patients with autoimmune hyperthyroidism. Here we describe a Caucasian woman who developed a bronchiolitis obliterans organizing pneumonia (BOOP)-like interstitial pneumonia after PTU administration for amiodarone-induced thyrotoxicosis. PATIENT FINDINGS: The patient was a 68 year-old woman who had been treated with amiodarone for chronic atrial fibrillation starting in May 2004. She had been a heavy smoker with a history of hypertension but no dust exposures. In October 2006, amiodarone was stopped after she developed thyrotoxicosis. In January 2007 serum thyroid-stimulating hormone (TSH) was 0.01 mIU/L (0.35-4.94) and free T4 was 17.5 pg/mL (7 to 15). She was initially started on methimazole and then changed to PTU after she developed pruritus. She developed severe dyspnea 9 months after starting PTU. At the time she was also taking warfarin, enalapril, and sotalol. Chest X-ray showed diffuse interstitial peripheral opacities and transbronchial lung biopsy revealed subacute lung injury with organizing pneumonia with hyperplasia of the alveolar type 2 pneumocytes, and characteristics of BOOP-like interstitial pneumonia. Signs and symptoms progressively improved after PTU discontinuation as confirmed at X-ray and computed tomography (CT) scan of the chest and by respiratory function tests. She has been recurrence free for 4 years after stopping PTU. SUMMARY: This woman of Caucasian ancestral origin developed BOOP-like interstitial pneumonia after PTU treatment for apparent amiodarone-induced thyrotoxicosis, with resolution of her lung disease after stopping PTU. Tests for TSH receptor antibodies, thyroid peroxidase antibodies, and antinuclear cytoplasmic autoantibody were negative. Thyroid ultrasound was consistent with thyroiditis without nodules. CONCLUSIONS: PTU-associated interstitial pneumonia is not limited to patients of Asian origin or those with autoimmune thyroid disease. PTU must be withdrawn in the presence of respiratory symptoms and documented interstitial pneumonia. X-ray films, CT-scan, respiratory function tests, and lung biopsy are needed to diagnose PTU-induced interstitial pneumonia with certainty and to monitor the evolution of the disease after PTU discontinuation. PMID- 22313429 TI - Denis Parsons Burkitt CMG, MD, DSc, FRS, FRCS, FTCD (1911-93) Irish by birth, Trinity by the grace of God. AB - Denis Parsons Burkitt, surgeon and research scientist, is a household name in the medical profession. Denis received his BA in 1933 and graduated as a physician in 1935 from Trinity College, Dublin. After serving as a surgeon in the Royal Army Medicine Corps during World War II, he worked as a surgeon and lecturer in Africa. It was in Africa that he developed exceptional observational and analytical skills, which led him to identify and formally develop a successful treatment for a childhood cancer that is now called Burkitt Lymphoma. The influence of Christianity in his life was huge. Throughout his life he remained extremely modest, attributing much of what he had achieved to the work of others. Denis's contributions to haemato-oncology remain salient today, and his discoveries continue to generate new research. Throughout his career he received some of the highest scientific honours from many different countries across the globe. PMID- 22313428 TI - Sterol composition and biosynthetic genes of the recently discovered photosynthetic alveolate, Chromera velia (chromerida), a close relative of apicomplexans. AB - Chromera velia is a recently discovered, photosynthetic, marine alveolate closely related to apicomplexan parasites, and more distantly to perkinsids and dinoflagellates. To date, there are no published studies on the sterols of C. velia. Because apicomplexans and perkinsids are not known to synthesize sterols de novo, but rather obtain them from their host organisms, our objective was to examine the composition of the sterols of C. velia to assess whether or not there is any commonality with dinoflagellates as the closest taxonomic group capable of synthesizing sterols de novo. Furthermore, knowledge of the sterols of C. velia may provide insight into the sterol biosynthetic capabilities of apicomplexans prior to loss of sterol biosynthesis. We have found that C. velia possesses two primary sterols, 24-ethylcholesta-5,22E-dien-3beta-ol, and 24-ethylcholest-5-en 3beta-ol, not common to dinoflagellates, but rather commonly found in other classes of algae and plants. In addition, we have identified computationally three genes, SMT1 (sterol-24C-methyltransferase), FDFT1 (farnesyl diphosphate farnesyl transferase, squalene synthase), and IDI1 (isopentenyl diphosphate Delta isomerase), predicted to be involved in sterol biosynthesis by their similarity to analogous genes in other sterol-producing eukaryotes, including a number of algae. PMID- 22313430 TI - The role of low-dose aspirin in the prevention of colorectal cancer. AB - INTRODUCTION: Colorectal cancer (CRC) is a prevalent disease that is associated with considerable morbidity and mortality. The progression of normal mucosa through adenomatous polyps to overt cancer can span for 10 - 15 years, making early detection, as well as the use of chemopreventive agents such as aspirin, an attractive option. The effects of aspirin in reducing CRC incidence and mortality have consistently been demonstrated in a number of studies. However, a greater understanding of how aspirin exerts its anti-cancer effects is warranted. AREAS COVERED: The aim of this non-systematic review, which was developed using published randomized and epidemiological studies, as well as key references known to the authors, was to consider the role of aspirin in CRC prevention. Areas covered include the effects of aspirin on cardiovascular disease, CRC and colorectal adenoma (CRA) prevention, mode of action of aspirin and the benefit-to risk of aspirin in disease prevention. EXPERT OPINION: Incorporating CRC and CRA benefits into coronary heart disease (CHD) risk scores would be particularly useful for determining the benefit-to-risk ratio for aspirin use in borderline cases. For instance, patients with an annual CHD risk around 0.7 - 1.4%, but with a high risk of colorectal neoplasm may benefit from aspirin. The strong association between CRC and age may also be useful for re-examining the benefit to-risk ratio for aspirin use in older patients. However, it has to be noted that a cancer prevention indication for aspirin is not approved regulatory-wise anywhere. PMID- 22313431 TI - The role of race and ethnicity in predicting length of hospice care among older adults. AB - BACKGROUND: The purpose of the study was to examine both direct and interactive roles of race/ethnicity with patients' characteristics (age, gender, relationship with caregiver, diagnosis, referral source, and payment type) in predicting length of hospice care. METHOD: This study included a total of 16,323 patients 65 years of age and older (M(age)=81.4, SD=8.3) who were served by a hospice in central Florida during a four-year period, 2002-2006. Survival analyses were conducted using the Cox proportional hazards model to predict the length of hospice care and test the interaction effects of race/ethnicity. RESULTS: The majority of subjects (83.5%) were white, 7.6% were African-American, and 8.9% were Hispanic. During the study period, 58.5% died. All patient characteristics were significantly associated with the length of hospice care (p < .05). Overall, Hispanics had the longest hospice stay (M=98.84 days), followed by African Americans (M=90.29) and whites (M=88.20). With the exception of African-American women who were no more likely to stay longer under hospice care than African American men, the women in this study stayed longer under hospice care than men did. Patients referred from long-term care (LTC) settings had shorter stays in hospice care compared to those referred by physicians in other settings. Additionally, African-Americans and Hispanics referred from LTC had significantly shorter hospice stays than those referred by primary physicians. CONCLUSION: In this limited sample of hospice patients, length of stay was longer for minority patients than white patients. PMID- 22313432 TI - The increasing importance of translational vision research in refractive surgery. AB - Addressing these business and financial components of research, we believe that including a section on translational vision research especially for refractive surgery will be a welcome addition to the readership of the Journal. Although the section "Translational Science" is new, the Journal has published a number of articles in past years that would have been ideal candidates for such a section. The inaugural Translational Science article in this month's issue is fron Santhiago and colleagues on short-term cell death and inflammation after intracorneal inlay implantation in rabbits. Although not all scientists are in agreement with the promotion of this term, the Journal aims to provide different outlooks and modern usage of translational research in this way to advance the field of refractive surgery. PMID- 22313433 TI - Glistenings on intraocular lenses. PMID- 22313434 TI - Absorption of UV-light by riboflavin solutions with different concentration. PMID- 22313435 TI - Intraocular femtosecond laser use in traumatic cataracts following penetrating and blunt trauma. AB - PURPOSE: To investigate the use of femtosecond laser cataract surgery in traumatic cataracts of different origin. METHODS: The first case developed acute traumatic cataract due to penetrating injury of the cornea and the anterior lens capsule; the second developed traumatic cataract 11 years after a penetrating corneal injury; and the third developed a "white" cataract 12 months after blunt ocular trauma. In all cases, 4.5-mm capsulorrhexis and corneal incisions were performed using a femtosecond laser system (Alcon LenSx Inc), and nucleus liquefaction with the laser was performed additionally in the second case. RESULTS: In all patients, a capsulorrhexis could be created with the femtosecond laser. Preexisting radial tears were present in the first case, but the remaining anterior capsule could be cut with the laser. The second and third cases showed an intact 4.5-mm capsulorrhexis. Corneal incisions were stable in all cases, and nucleus liquefaction was possible in the second case (grade 1-2 nuclear density). CONCLUSIONS: Results indicate that a femtosecond laser can be used successfully in certain instances of traumatic cataract after penetrating eye injury, even if an anterior capsule laceration is present, and also after blunt trauma resulting in "white" cataracts. PMID- 22313436 TI - Endogenous sex hormones and C-reactive protein in healthy Chinese men. AB - OBJECTIVE: To examine the association of endogenous sex hormones and sex hormone binding globulin (SHBG) with C-reactive protein (CRP) in Chinese men. DESIGN AND PARTICIPANTS: The study population comprised 1989 men at baseline recruitment of a population-based cohort in China. Participant information on risk factors was collected by a face-to-face interview and clinical examination. All subjects in the study were without taking any kind of medication for anti-inflammation purpose or treatment of hypogonadism and with CRP value less than 10 mg/l. Data were analysed using linear regression analyses. RESULTS: Higher levels of total testosterone (TT, beta = -0.114, 95%CI, -0.162 to -0.065), free testosterone (beta = -0.059, 95%CI, -0.106 to -0.012) and SHBG (beta = -0.116, 95%CI, -0.169 to -0.063) were statistically significantly related to lower levels of CRP, after adjustment for age, waist circumference (WC), triglycerides, high-density lipoprotein cholesterol, fasting glucose, insulin, smoking status, hypertension, diabetes and family history of hypertension or diabetes. In the subgroup of men with body mass index >= 27.5 kg/m(2) or with metabolic syndrome, findings for TT and SHBG were more pronounced, whereas the associations of TT with CRP were attenuated and nonstatistically significant among subjects with WC >= 90 cm or with insulin resistance. No associations were observed between estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and CRP. CONCLUSIONS: We have confirmed the association of androgens with reduced inflammation as measured by CRP in Chinese men. This is independent of conventional cardiovascular risk factors and is explained in part by markers of central obesity and insulin resistance, rather than metabolic syndrome. PMID- 22313437 TI - Predicting chronic kidney disease outcomes: are two estimated glomerular filtration rates better than one? AB - The National Kidney Foundation's (NKF) Kidney Disease Outcomes Quality Initiative (KDOQI) definition of chronic kidney disease (CKD), stages 3-5, requires 2 estimated glomerular filtration rates (eGFRs) <60 ml/min/1.73 m(2) more than 3 months apart. By requiring 2 eGFRs, the NKF definition reduced identification of people without chronic disease, which may have decreased identification of individuals with early CKD, but increased identification of those who ultimately have progression of CKD or require renal replacement therapy (RRT). Our objective was to determine whether 2 eGFR tests were better than 1 eGFR as a predictor of RRT, CKD progression, or death. This retrospective incident cohort study evaluates outcomes in adults with an initial eGFR <60 ml/min/1.73 m(2) and a second eGFR after 90 days by examining a third follow-up eGFR. For the 2086 patients in this study, the mean initial eGFR was 50.7 ml/min/1.73 m(2) and the mean second eGFR was 59.3 ml/min/1.73 m(2). More than 40% of the population (925) did not have CKD based upon their second eGFR. The initial eGFR was the best predictor of the third eGFR. There was no material difference in the ability to predict outcome measures between 1 versus 2 eGFR tests, regardless of eGFR value or associated comorbidities. Identifying patients with CKD is a critical step when beginning to implement population management strategies for those patients. Our findings illustrate some of the trade-offs in strategies inherent in methods that might be used to identify patients with CKD; 1 eGFR will identify patients about 5 months sooner, allowing additional time for nephrologist and other therapeutic intervention, but approximately doubles the population to be managed. PMID- 22313438 TI - The value of pharmacists in health care. AB - The American health care system is concerned about the rise of chronic diseases and related resource challenges. Management of chronic disease traditionally has been provided by physicians and nurses. The growth of the care management industry, in which nurses provide remote telephonic monitoring and coaching, testifies to the increasing need for care management and to the value of nonphysician clinicians. However, this model is challenged by a number of factors, including low enrollment and the growing shortage of nurses. The challenges to the traditional model are causing policy makers and payers to consider innovative models. One such model includes the pharmacist as an essential provider of care. Not only is the number of pharmacists growing, but they are playing an ever broader role in a variety of settings. This article broadly surveys the current state of pharmacist provision of care management services and highlights the increasingly proactive role played by Walgreen Co. toward this trend, using recently conducted research. Pharmacists are making a noticeable impact on and contribution to the care of chronic diseases by improving adherence to medications, a key factor in the improvement of outcomes. Literature also suggests that pharmacies are increasingly encouraging, expanding, and highlighting the role and contributions of their professional pharmacists. Although the role of the pharmacist in chronic care management is still developing, it is likely to grow in the future, given the needs of the health care system and patients. PMID- 22313439 TI - Quality of care, health care costs, and utilization among Medicare Part D enrollees with and without low-income subsidy. AB - The objective of this cross-sectional, retrospective, claims-based analysis was to evaluate disease-specific quality measures, use of acceptable therapies, and health care cost and utilization among Medicare Advantage Part D (MAPD) enrollees overall and by income/subsidy eligibility status. Individuals aged >=65 years with evidence of >=1 of 8 common conditions and continuously enrolled in a MAPD plan throughout 2007 were assigned to low-income/dually eligible (LI/DE) or non LI/DE cohorts. Quality of care metrics were calculated for asthma, chronic obstructive pulmonary disease (COPD), diabetes, and new episode depression. Persistence (proportion with percentage of days covered >=80%), compliance (proportion with medication possession ratio >=80%), health care costs, and utilization metrics were assessed by condition. All measures were evaluated for calendar year 2007. Bivariate comparisons were made between all LI/DE and non LI/DE subgroups. A total of 183,213 patients were included. Metrics showed deficiencies in quality of care overall but generally favored non-LI/DE patients. The proportion of patients filling acceptable medication was suboptimal for most conditions, ranging from 40% to 96% across conditions and cohorts, with COPD the lowest and heart failure (HF) the highest. LI/DE patients were significantly more likely than non-LI/DE patients to fill acceptable therapy in each disease group (P<0.001) except HF. Percentages persistent and compliant with acceptable therapies were lowest for asthma and COPD, and highest for HF; percentages were generally higher among LI/DE patients. Mean disease-specific health care costs ranged from $345 (hyperlipidemia) to $2086 (HF) and were significantly higher for LI/DE than for non-LI/DE enrollees (P<0.001) for all diseases except coronary artery disease and HF. Overall, quality indicators, use of acceptable medications, and persistence/compliance metrics were suboptimal. Quality metrics favored non-LI/DE patients but medication metrics favored LI/DE patients. With an aging population and increasing health care costs, the deficits identified highlight the need for comprehensive strategies to improve clinical and economic outcomes across diseases. PMID- 22313440 TI - Patterns of multimorbidity in primary care patients at high risk of future hospitalization. AB - Care management is seen as a promising approach to address the complex care needs of patients with multimorbidity. Predictive modeling based on insurance claims data is an emerging concept to identify patients likely to benefit from care management interventions. We aimed to identify and explore patterns of multimorbidity in primary care patients with high predicted risk of future hospitalizations in order to develop a primary care-based care management intervention. We conducted a retrospective cohort study to assess insurance claims data of 6026 patients from 10 primary care practices in Germany. We stratified the population by the predicted likelihood of hospitalization (LOH) using a diagnostic cost group-based case-finding software. Co-occurrence of chronic conditions in multimorbid patients with an upper-quartile LOH score was explored by extraction of mutually exclusive patterns. Predictive modeling identified multimorbid elderly patients with a high number of co-occurring chronic conditions (mean number 7.8 [SD 3.1]). Assessing co-occurrence of highly prevalent chronic conditions in 1407 multimorbid patients with upper-quartile LOH revealed 471 mutually exclusive patterns with low single frequencies. The observed prevalence significantly exceeded expected prevalence for patterns with causal comorbidity. Additionally, chronic pain (related to osteoarthritis) or depression could be identified as discordant co-occurring conditions in 80% (12/15) of the most common multimorbidity patterns. High-risk primary care patients suffer from heterogeneous individual patterns of co-occurring chronic conditions. Care management interventions will have to account for discordant co occurring conditions such as osteoarthritis and depression. PMID- 22313441 TI - Factors influencing health care utilization in older Hispanics with diabetes along the Texas-Mexico border. AB - Little is known about predictors of health care utilization for older Hispanics with chronic conditions. This study aimed to determine: (1) the level of health care access for older Hispanics with type 2 diabetes living in a US-Mexico border area; and (2) personal and health correlates to health care utilization (ie, physician visits, eye care, emergency room [ER] use). This was a cross-sectional study based on a community assessment conducted at a clinic, senior centers, and colonias. Colonias are impoverished neighborhoods with substandard living conditions along the US-Mexico border. Hispanics living in colonias are one of the most disadvantaged minority groups in the United States. The study sample consisted of 249 Hispanics age 60 years and older who have type 2 diabetes. Descriptive analyses, multiple linear regression, and generalized linear models were conducted. Older age (P = 0.02) and affordability of physician fees (P = 0.02) were significant correlates to more frequent physician visits. Factors significantly associated with eye care were being insured (P = 0.001) and reporting high cholesterol (P = 0.005). ER use was significantly associated with younger age (60-64 years old; P = 0.03) and suffering from hypertension (P = 0.02). Those who received diabetes education (P = 0.04) were less likely to use the ER. Identifying patterns of health care utilization services in aging underserved minorities who are disproportionately affected by diabetes may lead to culturally appropriate preventive practices and timely access to health care. Adequate health care access can decrease or delay the onset of diabetes complications in older Hispanics with type 2 diabetes who live along the US Mexico border. PMID- 22313442 TI - Shortcomings in public and private insurance coverage of diabetes self-management education and support. AB - The objective of this study is to present preliminary data to characterize public and private insurance coverage for diabetes self-management education (DSM Education) and diabetes self-management support (DSM Support). Representatives from Medicaid and 2 private insurance providers in 10 states provided coverage information for their insurance plans. Two states (the most populous state from the East and West coasts) were sampled purposively and 8 additional states from 4 geographic regions (northeast, southeast, northwest, southwest) were sampled at random. Representatives from each private insurer described both a premium and basic coverage plan. Thus, 10 Medicaid programs and 40 private insurance plans were represented. Information about Medicare coverage was accessed from publicly available documents. Restricted by physician certification of patient eligibility, Medicare coverage included 10 hours of DSM Education plus 3 hours of medical nutrition therapy (MNT) within a continuous 12-month period, and 4 hours of follow-up (2 hours DSM Education and 2 hours MNT) for each subsequent year. Only 22 of 40 sampled private insurance and 5 of 10 Medicaid plans covered DSM Education, which ranged from 7 to 20 hours of education per year. Medicaid and private plans often limited the amount of DSM Education or required patients to obtain a physician certification of eligibility. Other than on-demand access features, coverage of DSM Support was minimal. Public and private insurance coverage of DSM Education was neither widespread nor uniform, while coverage of DSM Support was scarce. PMID- 22313443 TI - Financial impact of population health management programs: reevaluating the literature. AB - Although many employers offer some components of worksite-based population health management (PHM), most do not yet invest in comprehensive programs. This hesitation to invest in comprehensive programs may be attributed to numerous factors, such as other more pressing business priorities, reluctance to intervene in the personal health choices of employees, or insufficient funds for employee health. Many decision makers also remain skeptical about whether investment in comprehensive programs will produce a financial return on investment (ROI). Most peer-reviewed studies assessing the financial impact of PHM were published before 2000 and include a broad array of program and study designs. Many of these studies have also included indirect productivity savings in their assessment of financial outcomes. In contrast, this review includes only peer-reviewed studies of the direct health care cost impact of comprehensive PHM programs that meet rigorous methodological criteria. A systematic search of health sciences databases identified only 5 studies with program designs and study methods meeting these selection criteria published after 2007. This focused review found that comprehensive PHM programs can yield a positive ROI based on their impact on direct health care costs, but the level of ROI achieved was lower than that reported by literature reviews with less focused and restrictive qualifying criteria. To yield substantial short-term health care cost savings, the longer term financial return that can credibly be associated with a comprehensive, prevention-oriented population health program must be augmented by other financial impact strategies. PMID- 22313444 TI - A problem-solving approach to effective insulin injection for patients at either end of the body mass index. AB - People with diabetes require skills and knowledge to adhere to medication regimens and self-manage this complex disease. Effective self-management is contingent upon effective problem solving and decision making. Gaps existed regarding useful approaches to problem solving by individuals with very low and very high body mass index (BMI) who self-administer insulin injections. This article addresses those gaps by presenting findings from a patient survey, a symposium on the topic of problem solving, and recent interviews with diabetes educators to facilitate problem-solving approaches for people with diabetes with high and low BMI who inject insulin and/or other medications. In practice, problem solving involves problem identification, definition, and specification; goal and barrier identification are a prelude to generating a set of potential strategies for problem resolution and applying these strategies to implement a solution. Teaching techniques, such as site rotation and ensuring that people with diabetes use the appropriate equipment, increase confidence with medication adherence. Medication taking is more effective when people with diabetes are equipped with the knowledge, skills, and problem-solving behaviors to effectively self-manage their injections. PMID- 22313445 TI - The Heart of New Ulm Project: using community-based cardiometabolic risk factor screenings in a rural population health improvement initiative. AB - Awareness of cardiovascular disease and diabetes risk factors can improve the health of individuals and populations. Community-based risk factor screening programs may be particularly useful for quantifying the burden of cardiometabolic risk in a given population, particularly in underserved areas. This study provided a description of a screening platform and how it has been used to monitor the cardiometabolic risk profile within the broader Heart of New Ulm Project, which is based in a rural Minnesota community. A cross-sectional, descriptive examination of baseline screening data indicated that 45% of the target population participated in the program over 8 months. Overall, 13% of the sample reported a personal history of diabetes or cardiovascular disease. Among the subset without active cardiometabolic disease, 35% were found to be at high risk for developing cardiovascular disease or type 2 diabetes over the next 8-10 years. A high prevalence of metabolic syndrome, high low-density lipoprotein cholesterol, obesity, and low fruit/vegetable consumption were of particular concern in this community. This article describes the use of screening results to inform the design of intervention programs that target these risk factors at both the community and individual levels. In addition, design considerations for future community-based cardiometabolic risk factor screening programs are discussed, with a focus on balancing program objectives related to health surveillance, research, and the delivery of preventive health care services. PMID- 22313447 TI - Cervical cancer screening behaviours among Thai women: results from a cross sectional survey of 2112 healthcare providers at Ramathibodi Hospital, Thailand. AB - This study compares factors and reasons related to female healthcare providers' behaviours on their cervical cancer screening using an analytic cross-sectional hospital-based study. A total of 2112 female healthcare providers in Ramathibodi hospital who do not have any cancer and were willing to participate in the study completed written consent and an anonymous questionnaire. We measured characteristics, medical history, life behaviour factors and reasons related to their cervical cancer screening behaviours. RESULTS: Five hundred of the 1365 responders (36.6%) have had at least one Pap test, meanwhile 848 responders (62.1%) have never had a Pap test and the remaining 17 responders (1.3%) did not complete answers. Between the two groups of responders who have had at least one Pap test and never had theirs Pap tests, their ages, careers and marital status influenced their cervical screening behaviours. Most of the reasons to refrain from their tests were their thoughtfulness of having no risks (27.1%), unnecessary (18.5%) and feeling shy (15.3%). In conclusion, the female hospital based healthcare providers should have more intensive cervical cancer screening behaviours even though having no risks. Their demographic characteristics, medical history and life behaviours influenced their decisions. Their thoughtfulness of no risks, unnecessary and feeling shy overcomes their cervical screening behaviours. PMID- 22313448 TI - Novel two-component gels of cetylpyridinium chloride and the bola-amphiphile 6 amino caproic acid: phase evolution and mechanism of gel formation. AB - A two-component gel resulting from the amphiphilic cationic surfactant cetylpyridinium chloride (CPC) in the presence of a structure-forming bola amphiphilic additive 6-aminocaproic acid (6-ACA) was realized and investigated. At a critical 6 wt % of 1:1 CPC:6-ACA, the yellow colored gel resulted from a 3:1 v/v CHCl(3):H(2)O critical binary solvent composition. The mixed amphiphilic system formed a 1:1 complex with a binding constant ~0.83 * 10(4) M(-1). Phase evolution and mechanism of gelation in the mixed CPC:6-ACA system was unraveled upon investigating the gel microstructure, based on spectroscopic, microscopic, and small-angle X-ray scattering (SAXS) investigations. The gel assembled as a lamellar organization, maintaining a loosely interdigitated bilayer structure of CPC and 6-ACA molecules through predominant charge transfer, H-bonding, and hydrophobic and intercomplex interactions. The SAXS pattern indicated a semicrystalline form to be the stable phase with alternating crystalline and amorphous layers; a novel mode of gelation with a widely disparate semicrystalline form of the lamellar gel was thus indicated, where the lamellar structure was deduced from the interplanar spacings. A transition from low viscosity reverse micellar solution to a yellow rigid gel upon aging was thus comprehended. The mixed amphiphile in varying polarity organic solvents in the presence of water indicated the nonconducive nature of gelation in very highly polar solvents, methanol, and DMF or, in very low polarity solvents, such as, cyclohexane and carbon tetrachloride. PMID- 22313449 TI - A hydrazine- and phosgene-free synthesis of tetrazinanones, precursors to 1,5 dialkyl-6-oxoverdazyl radicals. AB - A complementary approach to published synthetic methods for tetrazinanones, precursors to verdazyl radicals, is described herein. This approach uses carbohydrazide, a commercially available reagent, as a common starting material. Unlike previous methods described in the literature, this synthetic scheme does not rely on phosgene, phosgene substitutes, or the limited pool of commercially available monosubstituted hydrazines for its execution. A large variety of alkyl substitution patterns at the N-1 and N-5 positions of verdazyl radicals are possible, including both symmetrically and unsymmetrically substituted products. An initial condensation reaction of carbohydrazide with a specific aldehyde introduces the desired C-3 substituent in the final verdazyl radical product and protects the NH(2) groups during the subsequent N-1 and N-5 alkylation reactions. A succeeding methanolysis and concomitant ring-closing reaction gives the tetrazinanone. A number of known oxidation methods can then be employed to form the final verdazyl radical product. PMID- 22313450 TI - Poly(epsilon-caprolactone)-banded spherulites and interaction with MC3T3-E1 cells. AB - We report that protein adsorption, cell attachment, and cell proliferation were enhanced on spherulites-roughened polymer surfaces. Banded spherulites with concentric alternating succession of ridges and valleys were observed on spin coated thin films of poly(epsilon-caprolactone) (PCL) and two series of PCL binary homoblends composed of high- and low-molecular-weight components when they were isothermally crystallized at 25-52 degrees C. Their thermal properties, crystallization kinetics, and surface morphology were examined. The melting temperature (T(m)), crystallinity (chi(c)), crystallization rate, and spherulitic patterns showed strong dependence on the crystallization temperature (T(c)) and the blend composition. The surface roughness of the spherulites was higher when T(c) was higher; thus, the larger surface area formed in banded spherulites could adsorb more serum proteins from cell culture media. In vitro mouse preosteoblastic MC3T3-E1 cell attachment, proliferation, and nuclear localization were assessed on the hot-compressed flat disks and spherulites-roughened films of the high-molecular-weight PCL and one of its homoblends. The number of attached MC3T3-E1 cells and the proliferation rate were greater on the rougher surfaces than those on the flat ones. It is interesting to note that cell nuclei were preferentially, though not absolutely, located in or close to the valleys of the banded spherulites. The percentage of cell nuclei in the valleys was higher than 78% when the ridge height and adjacent ridge distance were ~350 and ~35 nm, respectively. This preference was weaker when the ridge height was lower or at a higher cell density. These results suggest that isothermal crystallization of semicrystalline polymers can be an effective thermal treatment method to achieve controllable surface roughness and pattern for regulating cell behaviors in tissue-engineering applications. PMID- 22313451 TI - Timing of skin testing after a suspected anaphylactic reaction during anaesthesia. AB - BACKGROUND: A delay of 4 to 6 weeks after a suspected anaphylactic reaction has commonly been recommended before performing skin testing. However, sometimes surgery cannot be delayed, and investigation must be done earlier. Recent recommendations suggest that skin testing can be performed immediately after a reaction. METHODS: We describe three cases in which skin testing was performed within 3 weeks after the suspected anaphylactic reaction. A literature review was undertaken to evaluate cases where skin testing was performed within 3 weeks of a suspected anaphylactic reaction during anaesthesia. RESULTS: Review of the literature did not give a definite answer to the optimal timing of skin testing after a suspected anaphylactic reaction during anaesthesia. CONCLUSIONS: Only positive skin tests can be taken into account, and there is little safety data to provide confidence in early skin testing. A protocol of how to act if urgent surgery is necessary is suggested. PMID- 22313452 TI - Genetically engineered transmissible influenza A/H5N1: a call for laboratory safety and security. PMID- 22313453 TI - Clinical strategies for the alleviation of contractures from a predictive mathematical model of dermal repair. AB - Hypertrophic scars arise when there is an overproduction of collagen during wound healing. These are often associated with poor regulation of the rate of programmed cell death (apoptosis) of the cells synthesizing the collagen or by an exuberant inflammatory response that prolongs collagen production and increases wound contraction. Severe contractures that occur, e.g., after a deep burn, can cause loss of function especially if the wound is over a joint such as the elbow or knee. Recently, we have developed a morphoelastic mathematical model for dermal repair that incorporates the chemical, cellular, and mechanical aspects of dermal wound healing. Using this model, we examine pathological scarring in dermal repair by first assuming a smaller than usual apoptotic rate for myofibroblasts, and then considering a prolonged inflammatory response, in an attempt to determine a possible optimal intervention strategy to promote normal repair, or terminate the fibrotic scarring response. Our model predicts that in both cases it is best to apply the intervention strategy early in the wound healing response. Further, the earlier an intervention is made, the less aggressive the intervention required. Finally, if intervention is conducted at a late time during healing, a significant intervention is required; however, there is a threshold concentration of the drug or therapy applied, above which minimal further improvement to wound repair is obtained. PMID- 22313454 TI - American Thyroid Association design and feasibility of a prospective randomized controlled trial of prophylactic central lymph node dissection for papillary thyroid carcinoma. AB - BACKGROUND: The role of prophylactic central lymph node dissection in papillary thyroid cancer (PTC) is controversial in patients who have no pre- or intraoperative evidence of nodal metastasis (clinically N0; cN0). The controversy relates to its unproven role in reducing recurrence rates while possibly increasing morbidity (permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury). METHODS AND RESULTS: We examined the design and feasibility of a multi-institutional prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC. Assuming a 7-year study with 4 years of enrollment, 5 years of average follow-up, a recurrence rate of 10% after 7 years, a 25% relative reduction in the rate of the primary endpoint (newly identified structural disease; i.e., persistent, recurrent, or distant metastatic disease) with central lymph node dissection and an annual dropout rate of 3%, a total of 5840 patients would have to be included in the study to achieve at least 80% statistical power. Similarly, given the low rates of morbidity, several thousands of patients would need to be included to identify a significant difference in rates of permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury. CONCLUSION: Given the low rates of both newly identified structural disease and morbidity after surgery for cN0 PTC, prohibitively large sample sizes would be required for sufficient statistical power to demonstrate significant differences in outcomes. Thus, a prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC is not readily feasible. PMID- 22313455 TI - In situ observation of oscillatory growth of bismuth nanoparticles. AB - We study the growth of Bi nanoparticles in an engineered precursor-scarce environment in a liquid cell at an elevated temperature (180 degrees C) using transmission electron microscopy. Observation reveals dynamics of oscillatory growth of individual nanoparticles, pairwise Ostwald ripening and anti-Ostwald ripening and a global collective oscillation. The experimental results suggest a mass-transport zone is present around each particle, which couples to the observed growth kinetics. This study shed light on a new route for system engineering to reverse particle coursing by Ostwald ripening. PMID- 22313456 TI - Long-term follow-up of patients with HIV-related diffuse large B-cell lymphomas treated in a phase II study with rituximab and CHOP. PMID- 22313457 TI - Regulation of cerebral vascular function by sirtuin 1. AB - OBJECTIVE: Endothelial dysfunction, associated with reduced nitric oxide bioavailability and oxidative stress, is a common feature of vascular-related diseases. Sirtuin 1 (SIRT1) is a protein deacetylase that has been shown to target endothelial nitric oxide synthase in large arteries and is protective during oxidative stress. However, within resistance-sized vessels, the expression and functional effects of SIRT1 remain unknown. METHODS: Immunoblotting and immunohistochemistry were used to determine SIRT1 expression and localization in cultured brain endothelial cells and intact rat middle cerebral artery. The influence of SIRT1 on vascular function was then studied in intact middle cerebral arteries using pressure myography. RESULTS: We report for the first time that SIRT1 is expressed in the resistance-sized vessels in the brain and is present in both the endothelium and smooth muscle. Pharmacological inhibition of SIRT1 demonstrated reduced endothelium-dependent dilation mediated by nitric oxide. However, endothelium-independent dilations were comparable in the presence and absence of SIRT1 block. CONCLUSIONS: Our results support a role for SIRT1 in endothelium-dependent relaxation in the cerebral vasculature and reveal a potential for SIRT1 as a therapeutic target in vascular-related diseases by restoring endothelial function. PMID- 22313459 TI - TPA induces the expression of EC-SOD in human monocytic THP-1 cells: involvement of PKC, MEK/ERK and NOX-derived ROS. AB - Extracellular-superoxide dismutase (EC-SOD) is a major SOD isozyme mainly present in the vascular wall. EC-SOD is also observed in monocytes/macrophages, and its high expression contributes to the suppression of atherosclerosis by scavenging superoxide. The molecular mechanisms governing cell-specific expression of EC-SOD are mostly unknown, while the anti-oxidative effect of EC-SOD is well recognized. In this study, we investigated the expression of EC-SOD during 12-O tetradecanoylphorbol-13-acetate (TPA)-induced monocytic differentiation of THP-1 cells, which is not expressing its gene in the basal phase. We confirmed the significant induction of EC-SOD in a TPA time-dependent manner, and that induction was completely blocked by pre-treatment with GF109203X, an inhibitor of protein kinase C, U0126 and PD98059, inhibitors of mitogen-activated protein kinase kinase/extracellular-signal regulated kinase. Moreover, we determined the involvement of NADPH oxidase-derived reactive oxygen species in that induction. Overall, we considered that these results may contribute to clarify the cell specific expression of EC-SOD. PMID- 22313458 TI - A.actinomycetemcomitans-induced periodontal disease promotes systemic and local responses in rat periodontium. AB - AIM: To characterize the histologic and cellular response to A. actinomycetemcomitans (Aa) infection. MATERIAL & METHODS: Wistar rats infected with Aa were evaluated for antibody response, oral Aa colonization, loss of attachment, PMN recruitment, TNF-alpha in the junctional epithelium and connective tissue, osteoclasts and adaptive immune response in local lymph nodes at baseline and 4, 5 or 6 weeks after infection. Some groups were given antibacterial treatment at 4 weeks. RESULTS: An antibody response against Aa occurred within 4 weeks of infection, and 78% of inoculated rats had detectable Aa in the oral cavity (p < 0.05). Aa infection significantly increased loss of attachment that was reversed by antibacterial treatment (p < 0.05). TNF-alpha expression in the junctional epithelium followed the same pattern. Aa stimulated high osteoclast formation and TNF-alpha expression in the connective tissue (p < 0.05). PMN recruitment significantly increased after Aa infection (p < 0.05). Aa also increased the number of CD8(+) T cells (p < 0.05), but not CD4(+) T cells or regulatory T cells (Tregs) (p > 0.05). CONCLUSION: Aa infection stimulated a local response that increased numbers of PMNs and TNF-alpha expression in the junctional epithelium and loss of attachment. Both TNF-alpha expression in JE and loss of attachment was reversed by antibiotic treatment. Aa infection also increased TNF-alpha in the connective tissue, osteoclast numbers and CD8(+) T cells in lymph nodes. The results link Aa infection with important characteristics of periodontal destruction. PMID- 22313460 TI - Conservative management of end-stage renal disease without dialysis: a systematic review. AB - PURPOSE: To summarize evidence on conservative, nondialytic management of end stage renal disease regarding 1) prognosis and 2) symptom burden and quality of life (QOL). METHODS: Medline, Cinahl, and Cochrane were searched for records indexed prior to March 1, 2011. Bibliographies of articles and abstracts from recent meetings were reviewed. Authors and nephrologists were contacted to identify additional studies. Articles were reviewed by two authors and selected if they described stage 5 chronic kidney disease (CKD) patients managed without dialysis, including one or more of the following outcomes: prognosis, symptoms, or QOL. Levels of evidence ratings were assigned using the SORT (Strength of Recommendation Taxonomy) system. Data was abstracted independently by two authors for descriptive analysis. RESULTS: Thirteen studies were included. In studies of prognosis, conservative management resulted in median survival of at least six months (range 6.3 to 23.4 months). Findings are mixed as to whether dialysis prolongs survival in the elderly versus conservative, nondialytic management. Any survival benefit from dialysis decreases with comorbidities, especially ischemic heart disease. Patients managed conservatively report a high symptom burden, underscoring the need for concurrent palliative care. Additional head-to-head studies are needed to compare the symptoms of age-matched dialysis patients, but preliminary studies suggest that QOL is similar. CONCLUSIONS: Conservative management is an important alternative to discuss when counseling patients and families about dialysis. Unlike withdrawal of dialysis in which imminent death is expected, patients who decline dialysis initiation can live for months to years with appropriate supportive care. PMID- 22313461 TI - The effects of newly developed linen dressings on decubitus ulcers. PMID- 22313491 TI - Sex at the origin: an Asian population of the rice blast fungus Magnaporthe oryzae reproduces sexually. AB - Sexual reproduction may be cryptic or facultative in fungi and therefore difficult to detect. Magnaporthe oryzae, which causes blast, the most damaging fungal disease of rice, is thought to originate from southeast Asia. It reproduces asexually in all rice-growing regions. Sexual reproduction has been suspected in limited areas of southeast Asia, but has never been demonstrated in contemporary populations. We characterized several M. oryzae populations worldwide both biologically and genetically, to identify candidate populations for sexual reproduction. The sexual cycle of M. oryzae requires two strains of opposite mating types, at least one of which is female-fertile, to come into contact. In one Chinese population, the two mating types were found to be present at similar frequencies and almost all strains were female-fertile. Compatible strains from this population completed the sexual cycle in vitro and produced viable progenies. Genotypic richness and linkage disequilibrium data also supported the existence of sexual reproduction in this population. We resampled this population the following year, and the data obtained confirmed the presence of all the biological and genetic characteristics of sexual reproduction. In particular, a considerable genetic reshuffling of alleles was observed between the 2 years. Computer simulations confirmed that the observed genetic characteristics were unlikely to have arisen in the absence of recombination. We therefore concluded that a contemporary population of M. oryzae, pathogenic on rice, reproduces sexually in natura in southeast Asia. Our findings provide evidence for the loss of sexual reproduction by a fungal plant pathogen outside its centre of origin. PMID- 22313492 TI - Evaluation of the antifungal susceptibility of Malassezia pachydermatis to clotrimazole, miconazole and thiabendazole using a modified CLSI M27-A3 microdilution method. AB - BACKGROUND: In this study, we evaluated the antifungal susceptibility of Malassezia pachydermatis to clotrimazole (CTZ), miconazole (MCZ), and thiabendazole (TBD), azole derivatives employed in aural formulations labeled for treatment of canine otitis. METHODS: The procedure for in vitro testing was based on the indications of the Clinical and Laboratory Standards Institute (CLSI) M27 A3 microdilution method. A lipid-enriched medium was employed to enhance the yeast growth (Christensen's urea broth, with 0.1% Tween 80 and 0.5% Tween 40 as the lipid sources), while the inoculums size corresponded to approximately 1-5 * 10(5) yeast cells/mL. Microplates were incubated at 37 degrees C and read 48 h after inoculation. Azole MICs inhibiting fungal growth were the lowest drug concentrations that showed an optical density of <= 50% of the (drug-free) growth control, as assessed by spectrophotometer (630 nm filter). RESULTS: All isolates were inhibited by the three azoles, with different minimum inhibitory concentration (MIC) values. Most isolates were inhibited by drug concentrations of 2-8 (CTZ), 1-4 (MCZ), or 16-32 (TBD) MUg/mL. These results are partially in agreement with the findings of previous studies, in which substantially higher/lower MICs were occasionally reported. This is likely because of the different methodologies employed. Such discrepancies may not apply to clinical situations, where the compounds are applied topically. CONCLUSION AND CLINICAL IMPORTANCE: The concept that clinical failure is linked to increased MICs is debatable, because significantly higher concentrations (in most cases at least 1,000 * the MIC) of the antifungals that were included in our study are routinely used in formulated products. PMID- 22313493 TI - Photodynamic antifungal chemotherapy. AB - The growing resistance against antifungal drugs has renewed the search for alternative treatment modalities, and antimicrobial photodynamic therapy (PDT) seems to be a potential candidate. Preliminary findings have demonstrated that dermatophytes and yeasts can be effectively sensitized in vitro and in vivo by administering photosensitizers (PSs) belonging to four chemical groups: phenothiazine dyes, porphyrins and phthalocyanines, as well as aminolevulinic acid, which, while not a PS in itself, is effectively metabolized into protoporphyrin IX. Besides efficacy, PDT has shown other benefits. First, the sensitizers used are highly selective, i.e., fungi can be killed at combinations of drug and light doses much lower than that needed for a similar effect on keratinocytes. Second, all investigated PSs lack genotoxic and mutagenic activity. Finally, the hazard of selection of drug resistant fungal strains has been rarely reported. We review the studies published to date on antifungal applications of PDT, with special focus on yeast, and aim to raise awareness of this area of research, which has the potential to make a significant impact in future treatment of fungal infections. PMID- 22313494 TI - Unassisted transport of N-acetyl-L-tryptophanamide through membrane: experiment and simulation of kinetics. AB - Cellular transport machinery, such as channels and pumps, is working against the background of unassisted material transport through membranes. The permeation of a blocked tryptophan through a 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) membrane is investigated to probe unassisted or physical transport. The transport rate is measured experimentally and modeled computationally. The time scale measured by parallel artificial membrane permeation assay (PAMPA) experiments is ~8 h. Simulations with the milestoning algorithm suggest mean first passage time (MFPT) of ~4 h and the presence of a large barrier at the center of the bilayer. A similar calculation with the solubility-diffusion model yields a MFPT of ~15 min. This permeation rate is 9 orders of magnitude slower than the permeation rate of only a tryptophan side chain (computed by us and others). This difference suggests critical dependence of transport time on permeant size and hydrophilicity. Analysis of the simulation results suggests that the permeant partially preserves hydrogen bonding of the peptide backbone to water and lipid molecules even when it is moving closer to the bilayer center. As a consequence, defects of the membrane structure are developed to assist permeation. PMID- 22313495 TI - "Have a drink, you'll feel better." Predictors of daily alcohol consumption among extraverts: the mediational role of coping. AB - An abundance of information exists pertaining to individual differences in college drinking behaviors with much attention being provided to the role of personality. However, plausible explanations for what prompts engagement in or avoidance of these behaviors have remained largely ambiguous or underexplored, particularly with respect to extraversion (E). Research has since explored how coping behaviors contribute to these associations. The present study built on this research by evaluating differences in daily alcohol consumption as a function of coping choice. The mediational effects of two specific strategies frequently observed in high E individuals (i.e., problem-focused coping and social support) were examined. Using a daily diary approach, 365 undergraduates reported their most stressful experience, how they coped with it, and the number of drinks consumed for five consecutive days. Resulting multilevel-models were consistent with hypotheses indicating the relationship between E and alcohol consumption was partially mediated by problem-focused and support-seeking strategies. The use of problem-focused coping by high E individuals was associated with lower levels of daily alcohol consumption, suggesting this strategy may play a protective role in influencing drinking behaviors. Conversely, the positive effect observed for social support approached significance (p=.054) and was indicative of a potential risk-factor for daily alcohol consumption. PMID- 22313497 TI - Power and meaninglessness. PMID- 22313496 TI - Vasopressors for the management of hypotension after spinal anesthesia for elective caesarean section. Systematic review and cumulative meta-analysis. AB - BACKGROUND: Phenylephrine use has been recommended over ephedrine for the management of hypotension after spinal anesthesia for elective caesarean section. The evidence for this is rather limited because in previous trials, pH was significantly lower after ephedrine, but absolute values were still within normal range. We pooled the available data to define maternal and neonatal effects of the two vasopressors. METHODS: Literature was identified by a systematic search. Hypotension, hypertension, and bradycardia of the mothers, fetal acidosis defined as a pH < 7.20, and the continuous variables base excess (BE) and arterial pCO(2) of the neonates were recorded. Meta-analysis using the random effects model was performed, and the weighted mean difference (WMD) or risk ratio (RR), and 95% confidence interval (95% CI) were calculated. RESULTS: The criteria for eligibility were fulfilled by 20 trials including 1069 patients. The RR of true fetal acidosis was 5.29 (95%CI 1.62-17.25, ) for ephedrine vs. phenylephrine (P = 0.006). BE values after ephedrine use were significantly lower than after phenylephrine (WMD -1.17; 95% CI -2.01 - -0.33). Umbilical artery pCO(2) did not differ. Mothers treated with ephedrine had a lower risk for bradycardia (RR 0.17; 95%CI 0.07-0.43; P = 0.004). No differences between vasopressors were observed for hypotension and hypertension. CONCLUSIONS: Our analysis could clearly demonstrate a decreased risk of fetal acidosis associated with phenylephrine use. In addition with our findings for BE, this suggests a favorable effect of phenylephrine on fetal outcome parameters. The mechanism of pH depression is not related to pCO(2) . PMID- 22313498 TI - Long distance conduction of vasodilation: a passive or regenerative process? AB - The mechanism enabling coordination of the resistance of feed arteries with microcirculatory arterioles to rapidly regulate tissue blood flow in line with changes in metabolic demand has preoccupied scientists for a quarter of a century. As experiments uncovered the underlying electrical events, it was frequently questioned how vasodilation could conduct over long distances without appreciable attenuation. This perspective reviews the data pertinent to this phenomenon and provides evidence that this remarkable response could be made possible by a simple mechanism based on the steep relationship between membrane potential and calcium entry demonstrated by the voltage-dependent calcium channels which mediate the control of vascular tone in vivo. PMID- 22313499 TI - Venous thromboembolism after radical prostatectomy: the effect of surgical caseload. AB - What's known on the subject? and What does the study add? Several risk factors increase VTE after RP: advanced age, comorbidities such as cardiopulmonary disease, rheumatologic diseases, prior history of VTE, more advanced prostate cancer, and simultaneous pelvic lymph node dissection. To date, the effect of annual surgical caseload (ASC), an established determinant of various RP outcomes, has not been tested. A previous study showed in adjusted analyses that patients operated for colorectal cancer by very high ASC surgeons were 60% less likely to suffer a VTE than those operated by low ASC surgeons. Moreover, some authors hypothesized that laparoscopy may contribute to a higher risk of VTE, due to peritoneal insufflation, reverse Trendelenburg position and prolonged operative time. The VTE rates reported in the current population-based study closely reflect those reported in institutional series. Moreover, we validated the practice-makes-perfect concept, since ASC was linked to VTE. We could not detect statistically significantly differences between minimally invasive radical prostatectomy (MIRP) patients and others. Our results indicate that lower rates of VTE should be expected in patients treated by high ASC surgeons. Our findings suggest that VTE-specific processes of care need to be improved, with the intent of reaching the level recorded in patients treated by high ASC surgeons. Finally, MIRP seems to be no risk factor for VTE. OBJECTIVE: To examine the effect of annual surgical caseload (ASC) on the likelihood of venous thromboembolism (VTE) after radical prostatectomy (RP). PATIENTS AND METHODS: Between 1999 and 2008, 36 699 RPs were performed in the state of Florida. Logistic regression models predicting the likelihood of VTE were fitted. Covariates included year of surgery, age, race, baseline Charlson Comorbidity Index (CCI), lymph node dissection, ASC and surgical approach. RESULTS: The overall VTE rate was 0.3%. It was higher in patients operated within the low (0.4%) and intermediate (0.3%) ASC tertile than in those operated within the high-ASC tertile (0.1%, P < 0.001). Mortality rate was 6.0% in patients with VTE vs 0.1% in others (P < 0.001). Median length of stay and median total hospital charges were 9 vs 3 days (P < 0.001) and $51 571 vs $24 943 (P < 0.001) in patients with VTE vs others, respectively. In multivariable analyses predicting VTE, patients operated on by low-ASC surgeons were at higher risk of VTE than those operated on by high-ASC surgeons (odds ratio [OR] = 3.78, P < 0.001). Additionally, black patients were more likely to experience a VTE (OR = 1.80, P = 0.023). Patients with CCI >= 1 were also more likely to experience a VTE than others (OR = 1.65, P = 0.016). Conversely, patients who had undergone minimally invasive radical prostatectomy were not more likely to experience a VTE than those who had undergone open RP (OR = 1.97, P = 0.086). CONCLUSIONS: RP by high-ASC surgeons exerts a protective effect on the likelihood of VTE. Additionally, VTE is associated with higher mortality, prolonged length of stay and increased hospital charges. PMID- 22313501 TI - Is it time to miss the target for prostate cancer? PMID- 22313500 TI - Prey-race drives differentiation of biotypes in ant-eating spiders. AB - 1. Disruptive natural selection resulting from specialization on different hosts is recognized as one of the most important driving forces in the diversification of herbivores and parasites. It has been proposed that a similar mechanism could apply to carnivorous predators too, although the evidence is still lacking. 2. Here, we show that the differentiation of biotypes of specialized ant-eating spiders of the genus Zodarion has probably been induced by prey-shifting. We focused on two forms of one species Z. styliferum from the Iberian Peninsula that presumably represent ecological races. We conducted geographic, ecological, venom oriented, reproductive and genetic divergence analysis among multiple populations collected at a number of sites across Portugal and Madeira. 3. Geographic analysis revealed that the two forms occur in mosaic sympatry. Each form was found to associate in nature with a different ant species in a different habitat. Specifically, the styliferum form hunted predominantly Messor ants, and the extraneum form hunted mainly Camponotus ants. Laboratory experiments revealed that the two forms exhibit a significant preference for attacking focal ants, demonstrating higher paralysis efficiency, and also show different venom composition. Cross-mating of the two forms was significantly less likely than between pairs of the same form, suggesting moderate assortative mating. Phylogenetic analyses indicate low genetic differentiation of the two forms and parallel-repeated evolution of biotypes. 4. Adaptive prey-shifting correlated with habitat preference are at present the most valid explanations for biotype formation in Zodarion. The speciation of ant-eating Zodarion spiders thus appears to follow a scenario similar to that of host-shifting in parasites and herbivores. PMID- 22313502 TI - Intravesical gemcitabine therapy for non-muscle invasive bladder cancer (NMIBC): a systematic review. AB - * Intravesical immunotherapy or chemotherapy for non-muscle invasive bladder cancer is a well-established treatment for preventing or delaying tumour recurrence after tumour resection. However, up to 70% of patients may fail and new intravesical agents with improved effectiveness are needed. Gemcitabine is a relatively new anticancer drug that has shown activity against bladder cancer. * To systematically review the literature on the effectiveness and toxicity of intravesical gemcitabine for non-muscle invasive bladder cancer (NMIBC). * MEDLINE, EMBASE, CINAHL, the Cochrane database of systematic reviews, LILACS, SCOPUS, BNI, Biomed Central, Web of Science and BIOSIS were searched to identify trials of intravesical gemcitabine for the treatment of NMIBC. Also searched were meeting proceedings, international guidelines and trial registries. Data on authors, study design, patient characteristics, interventions and outcome data relating to tumour recurrence, disease progression, survival and adverse events were extracted from relevant studies. * Six relevant randomised trials were identified with the number of patients randomised in each trial varying from 30 to 341 (total 704). All trials compared gemcitabine to active controls and varied in the reporting of outcomes. * The first was a marker lesion study which reported greater tumour response rates when intravesical gemcitabine (2 g) was given as three bi-weekly doses (36%) or six weekly doses (40%) compared with a single dose (9%). * One study compared a single postoperative instillation of intravesical gemcitabine with a saline placebo in 341 patients and found no significant difference in the rates of tumour recurrence (28% vs 39%, respectively) or recurrence-free survival (hazard ratio 0.95, 95% confidence interval 0.64-1.39, P= 0.77). The rate of progression to invasive disease was greater with gemcitabine (2.4% vs 0.8%). * A further trial compared gemcitabine with intravesical mitomycin C (MMC) and reported that the rates of recurrence (28% vs 39%) and progression (11% vs 18%) were lower with gemcitabine but did not reach statistical significance. The overall incidence of adverse events was significantly less with gemcitabine (38.8% vs 72.2%, P= 0.02). * Three trials compared gemcitabine with intravesical bacille Calmette-Guerin (BCG) but a meta analysis was not possible due to clinical heterogeneity. * In untreated patients at intermediate risk of recurrence (primary Ta-T1, no carcinoma in situ) one trial showed that gemcitabine and BCG were similar with respective recurrence rates of 25% and 30% (P= 0.92) and overall progression equal. Dysuria (12.5% vs 45%, P < 0.05) and frequency (10% vs 45%, P < 0.001) were significantly less with gemcitabine. * In a second trial of high-risk patients the recurrence rate was significantly greater with gemcitabine compared with BCG (53.1% vs 28.1%, P= 0.04%) and the time to recurrence significantly shorter with gemcitabine (25.5 vs 39.4 months, P= 0.042). * Finally, in a third trial of high-risk patients who had failed previous intravesical BCG therapy, gemcitabine was associated with significantly fewer recurrences (52.5% vs 87.5%, P= 0.002) and a longer time to recurrence (3.9 vs 3.1 months, P= 0.9) compared with BCG. Progression rates were similar in both groups (33% vs 37.5%, P= 0.12) with no significant differences in grade 2 or 3 toxicities. * The data from several observational studies confirm the pharmacology of gemcitabine as an intravesical agent whilst others report the activity of gemcitabine in terms of tumour recurrence. However, these studies are inherently biased and these data should be interpreted appropriately. * In conclusion a single study suggests that in NMIBC multiple doses of intravesical gemcitabine reduce tumour recurrences to a greater extent than a single dose. * In contrast, a single dose immediately after surgery is ineffective based on one study. Gemcitabine may be more active than MMC with a lower toxicity profile. * Compared with intravesical BCG therapy, gemcitabine had similar effects in intermediate-risk patients, less effective in high-risk patients and superior in BCG-refractory patients. However, each randomised trial identified represents a different clinical setting in NMIBC and therefore the evidence base is limited. Consequently these data should be interpreted with caution until further corroborative evidence becomes available. * Intravesical gemcitabine is a promising drug that may add to the urologist's options in treating patients with NMIBC. PMID- 22313503 TI - A three-step technique for umbilicoplasty in a patent urachus. PMID- 22313504 TI - Circumcision-generated emotions bias medical literature. PMID- 22313507 TI - T cell depletion utilizing CD34(+) stem cell selection and CD3(+) addback from unrelated adult donors in paediatric allogeneic stem cell transplantation recipients. AB - CD34-selected haploidentical and unrelated donor allogeneic stem cell transplantation (AlloSCT) in paediatric recipients is associated with sustained engraftment and low risk of acute graft-versus-host disease (aGVHD), but limited by delayed immune reconstitution and increased risk of viral and fungal infection. The optimal dose of donor T cells to prevent graft failure and minimize risk of early opportunistic infection and post-transplant lymphoproliferative disorder (PTLD), while avoiding severe aGVHD, remains unknown. We prospectively studied CD34-selected 8-10/10 human leucocyte antigen (HLA)-matched unrelated donor (MUD) peripheral blood stem cell transplantation (PBSCT) in a cohort of 19 paediatric AlloSCT recipients with malignant (n = 13) or non-malignant (n = 6) diseases. T cells were added back to achieve total dose 1.0-2.5 * 10(5) CD3(+) /kg. GVHD pharmacoprophylaxis consisted only of tacrolimus. All patients engrafted neutrophils. Probabilities of grade II-IV aGVHD, limited chronic GVHD (cGVHD), and extensive cGVHD were 15.8%, 23.3%, and 0%, respectively. One patient developed PTLD. One-year infection-related mortality was 5.6%. T cell immune reconstitution was delayed. One-year overall survival was 82.3%. Five patients with malignant disease ultimately died from progressive disease. CD34-selected MUD PBSCT using a defined dose of T cell add back resulted in high rates of engraftment and low risk of grade II-IV aGVHD, early transplantation-related mortality, and extensive cGVHD. PMID- 22313508 TI - The influence of steam cleaning procedures on the surface roughness of commonly used type III dental stone for the fabrication of removable dentures. AB - OBJECTIVE: This study investigated the possible detrimental effects of steam treatment on the surface of type III dental stone, which is a common laboratory material used for the construction of removable dentures. MATERIAL AND METHODS: Forty dental stone specimens were prepared and divided into four groups (A, B, C and D), and group A was used as the control group. The other groups were treated with steam from a standard distance for varying durations (30, 60 and 120 s). RESULTS: The duration of steam cleaning significantly increased Ra values (F = 63.150, p = 0.000). Similarly, the duration of steam application was directly correlated with the weight changes (F = 17.721, p = 0.000). A significant amount of dental stone can be removed from the surface while treating with steam. CONCLUSION: These studies demonstrated that expanded periods of steam cleaning cause weight loss and abrade the surface of type III dental stones; therefore, these devices should be used with caution during denture fabrication procedures. PMID- 22313509 TI - Problem based learning in mental health nursing: the students' experience. AB - Problem based learning (PBL) is well established within the field of health-care education for professionals worldwide, although little has been done to explore the experiences of students undertaking a PBL course in mental health nursing. Without firm evidence of the benefits of PBL, educationalists in mental health might be reluctant to view it as an option in curricula design. This U.K. study examined the experiences of pre-registration post-graduate mental health student nurses undertaking a 2-year educational course in which all teaching and assessment followed a PBL philosophy. Focus groups were used throughout the course to elicit in-depth qualitative data that was analysed by applying a constant comparative method. The analysis of the data uncovered the following broad themes: 'moves to autonomy, 'surviving the groups' and 'the impact of PBL'. The findings show that participants had mainly positive experiences and gained a range of study and interpersonal skills central to mental health nursing. Participants described initial anxieties resulting from engagement in PBL. However, they increasingly gained confidence in this approach, exercising increasing control over the PBL process. Despite this increased autonomy, participants continued to value the input of skilled facilitators. A recurring issue centred on the potential for interpersonal conflict within the student group and its impact on their learning. It is suggested that more research is needed examining the use of PBL in mental health nursing. PMID- 22313510 TI - Mycoheterotrophic interactions are not limited to a narrow phylogenetic range of arbuscular mycorrhizal fungi. AB - The majority of achlorophyllous mycoheterotrophic plant species associate with arbuscular mycorrhizal fungi (AMF). Previous studies have shown that some species are highly specialized towards narrow lineages of AMF and have suggested that only particular lineages of these fungi are targeted by mycoheterotrophic plants. To test this hypothesis, we analyzed all available partial SSU sequences of AMF associated with mycoheterotrophic plants including data from 13 additional specimens from French Guiana, Gabon and Australia. Sequences were assigned to 'virtual taxa' (VT) according to the MaarjAM database. We found that 20% of all known Glomeromycota VT are involved in mycoheterotrophic interactions and the majority of associations involve Glomeraceae (Glomus Group A) fungi. While some mycoheterotrophic plant species have been found growing with only a single VT, many species are able to associate with a wide range of AMF. We calculated significant phylogenetic clustering of Glomeromycota VT involved in mycoheterotrophic interactions, suggesting that associations between mycoheterotrophic plants and AMF are influenced by the phylogenetic relationships of the fungi. Our results demonstrate that many lineages of AMF are prone to exploitation by mycoheterotrophic plants. However, mycoheterotrophs from different plant lineages and different geographical regions tend to be dependent on lineages of AMF that are phylogenetically related. PMID- 22313511 TI - Brain banks as key part of biochemical and molecular studies on cerebral cortex involvement in Parkinson's disease. AB - Exciting developments in basic and clinical neuroscience and recent progress in the field of Parkinson's disease (PD) are partly a result of the availability of human specimens obtained through brain banks. These banks have optimized the methodological, managerial and organizational procedures; standard operating procedures; and ethical, legal and social issues, including the code of conduct for 21st Century brain banking and novel protocols. The present minireview focuses on current brain banking organization and management, as well as the likely future direction of the brain banking field. We emphasize the potentials and pitfalls when using high-quality specimens of the human central nervous system for advancing PD research. PD is a generalized disease in which alpha synuclein is not a unique component but, instead, is only one of the players accounting for the complex impairment of biochemical/molecular processes involved in metabolic pathways. This is particularly important in the cerebral cortex, where altered cognition has a complex neurochemical substrate. Mitochondria and energy metabolism impairment, abnormal RNA, microRNA, protein synthesis, post translational protein modifications and alterations in the lipid composition of membranes and lipid rafts are part of these complementary factors. We have to be alert to the possible pitfalls of each specimen and its suitability for a particular study. Not all samples qualify for the study of DNA, RNA, proteins, post-translational modifications, lipids and metabolomes, although the use of carefully selected samples and appropriate methods minimizes pitfalls and errors and guarantees high-quality reserach. PMID- 22313512 TI - Manganese toxicity with ephedrone abuse manifesting as parkinsonism: a case report. AB - INTRODUCTION: Neurologic consequences of manganese toxicity have been recognized since 1837. A new form of presumed manganese poisoning has been reported in drug addicted persons from Eastern Europe and the Baltic states who have intravenously injected self-prepared methcathinone hydrochloride (ephedrone), which is synthesized from pseudoephedrine hydrochloride using potassium permanganate as a potent oxidant. This clinical syndrome is under-recognized in Western Europe and there are no reported cases in the literature from Ireland. CASE PRESENTATION: We report a 30-year-old Eastern European man who presented with a two-year history of gait disturbance. A neurological assessment revealed features of parkinsonism which included hypophonia, hypomimia, mild bradykinesia and rigidity with no resting tremor. He held his arms slightly abducted from his sides when walking, with a reduction in arm swing. Magnetic resonance imaging of his brain showed a high signal on T1 in the globus pallidus and serum manganese levels were raised. He had no response to levodopa. CONCLUSION: Manganism secondary to ephedrone abuse causing parkinsonism has emerged in Western Europe in recent years due to mass immigration and often remains unrecognized. This paper highlights the various features of this rare cause of parkinsonism and aids in its recognition and subsequent diagnosis. Neurologists in Western Europe will increasingly encounter such patients. PMID- 22313513 TI - Adolescent adherence to psychosocial treatment: mental health clinicians' perspectives on barriers and promoters. AB - Poor adolescent adherence to mental health psychosocial treatment significantly undermines effectiveness. Approximately one-third of all youth drop out or prematurely terminate from psychosocial treatment. This study examined youth adherence to psychosocial treatment from the perspective of community-based mental health clinicians (n =34) interviewed across three focus groups. A grounded theory analysis was applied to investigate the promoters and barriers influencing adolescent adherence to treatment. Clinicians identified four domains (adolescent, family, clinician, and agency) that serve as promoters and barriers to adherence. Barriers to adherence were located primarily in adolescent and family domains, whereas promoters were attributed within the clinician domain. Understanding of the complex influences on adolescent adherence may facilitate increased awareness and intervention options for clinicians. PMID- 22313514 TI - Drug-administration sequence of target-controlled propofol and remifentanil influences the onset of rocuronium. A double-blind, randomized trial. AB - BACKGROUND: Remifentanil is known to cause bradycardia and hypotension, as well as the decreases of cardiac output (CO). We hypothesized that hemodynamic suppression by remifentanil would affect the onset time of rocuronium. This study investigated whether the onset of rocuronium was influenced by the drug administration sequence during induction of anesthesia with target-controlled infusion of propofol and remifentanil. METHODS: Healthy adult patients (n = 126) undergoing elective surgery under general anesthesia were randomized into two groups according to drug-administration sequence. In Remi-Pro-Rocu group (n = 62), remifentanil was infused first, followed by propofol. Then, rocuronium was administered lastly. In Pro-Rocu-Remi group (n = 64), propofol, rocuronium, and remifentanil were given in that order. As a primary outcome, the onset time of rocuronium was measured. Mean arterial pressure (MAP), heart rate (HR), CO, and stroke volume were recorded before anesthesia (T1), at injection of rocuronium (T2), immediately before and after intubation (T3 and T4). RESULTS: In Remi-Pro Roc group, the onset of rocuronium was delayed significantly compared with Pro Rocu-Remi group [median (interquartile range); 130 (105-150) vs. 90 (71-100) s, P < 0.001]. At the time of rocuronium injection (T2), MAP, HR, and CO were significantly lower in Remi-Pro-Rocu group than Pro-Rocu-Remi group (P < 0.001). CONCLUSION: The onset time of rocuronium is prolonged significantly by early administration of remifentanil during target-controlled infusion of propofol and remifentanil, and it may be due to the decreased CO caused by remifentanil. PMID- 22313515 TI - Debulking surgery in the setting of very high-risk prostate cancer scenarios. AB - What's known on the subject? and What does the study add? Nowadays radical prostatectomy (RP) is considered an effective treatment in high-risk prostate cancer (PCa) and the indications for a surgical approach are expanding, even in cases of very high PSA or node-positive disease. We explored the outcomes of debulking surgery in the setting of these very high-risk PCa patients, in order to assess its feasibility. This review confirms the important role achieved by surgery in the complex setting of patients with very high-risk PCA. Excellent survival rates have been reported, even when PSA exceeds 100 ng/mL. The completion of RP with lymphadenectomy might give a survival benefit in patients who were found intraoperatively to be node-positive. Furthermore, salvage RP confirmed to be the most effective treatment option after RT failure. On the contrary, up-to-date surgery of isolated nodal recurrences has shown only little benefit. Finally, there is no evidence supporting the efficacy of debulking surgery in metastatic or in hormone-refractory tumours. An accurate selection of the patient is essential. OBJECTIVE: To conduct a critical analysis of the available literature on the feasibility of debulking surgery in the setting of very high-risk prostate cancer (PCa) scenarios. PATIENTS AND METHODS: We performed a systematic literature search of PubMed and Embase using combinations of the following keywords: radical prostatectomy, surgery, high-risk, high PSA (prostate-specific antigen), radiorecurrent, hormone-refractory, metastatic prostate cancer, salvage. With the term 'very high-risk PCa' we indicated a clinical disease beyond the common definition of high-risk PCa, i.e. any clinical stage > T3, N0 or N+, any PSA level > 50 ng/mL and any recurrent disease after primary treatment. RESULTS: Radical prostatectomy (RP) achieved excellent survival rates in high-risk PCa, even in patients with very high PSA level. The completion of RP with lymphadenectomy might give a survival benefit in patients who were found intraoperatively to be node-positive. Salvage RP was confirmed to be the most effective treatment option after radiotherapy failure, with increased functional outcomes and decreased side-effects in the most recent series. Surgery of isolated nodal recurrences after previous radical therapy has shown little benefit according to the few available series. There is no evidence supporting the efficacy of debulking surgery in metastatic or hormone-refractory PCa. CONCLUSION: Debulking surgery achieved an important role in several aggressive PCa scenarios. An accurate selection of the patient is essential. PMID- 22313516 TI - Beneficial effect of amantadine on postoperative pain reduction and consumption of morphine in patients subjected to elective spine surgery. AB - OBJECTIVE: To analyze the effect of coadministration of morphine and amantadine on postoperative pain reduction and morphine consumption in patients after elective spine surgery. METHODS: In double-blinded study, 60 patients (ASA physical status I-II) were randomized into two groups. Group A was given oral amantadine 50 or 100 mg 1 hour before surgery and 8, 20, 32 hours after operation. Group P received placebo at identical times. Pain was assessed using numerical rating scale before first administration of morphine and in 2, 3, 4, 6, 24, and 48 hours after operation. The amounts of morphine consumed were recorded up to 48 hours after surgery. Blood samples were taken twice in 2 hours after surgery and plasma levels of morphine and its main metabolites were measured. RESULTS: As compared with placebo, amantadine significantly reduced intra operative Fentanyl use and sensation of postoperative pain. Up to 48 hours after operation, the cumulative consumption of morphine was 25% lower in the amantadine group. Moreover, intensity of nausea and vomiting tended to be lower in A group. Starting from 12th hour after surgery, the level of postoperative sedation was lower in patients who received amantadine, as compared with placebo group. No significant differences in plasma levels of morphine ant its metabolites were observed between A and P groups. CONCLUSIONS: Pre- and postoperative administration of amantadine significantly reduced fentanyl use during operation, as well as reduced the postoperative pain and decreased morphine consumption in young patients undergoing orthopedic surgery. PMID- 22313517 TI - A clusterwise simultaneous component method for capturing within-cluster differences in component variances and correlations. AB - This paper presents a clusterwise simultaneous component analysis for tracing structural differences and similarities between data of different groups of subjects. This model partitions the groups into a number of clusters according to the covariance structure of the data of each group and performs a simultaneous component analysis with invariant pattern restrictions (SCA-P) for each cluster. These restrictions imply that the model allows for between-group differences in the variances and the correlations of the cluster-specific components. As such, clusterwise SCA-P is more flexible than the earlier proposed clusterwise SCA-ECP model, which imposed equal average cross-products constraints on the component scores of the groups that belong to the same cluster. Using clusterwise SCA-P, a finer-grained, yet parsimonious picture of the group differences and similarities can be obtained. An algorithm for fitting clusterwise SCA-P solutions is presented and its performance is evaluated by means of a simulation study. The value of the model for empirical research is illustrated with data from psychiatric diagnosis research. PMID- 22313518 TI - Human Plasmodium knowlesi infection in Ranong province, southwestern border of Thailand. AB - BACKGROUND: Plasmodium knowlesi, a simian malaria parasite, has been reported in humans in many Southeast Asian countries. In Thailand, most of the limited numbers of cases reported so far were from areas near neighbouring countries, including Myanmar. METHODS: Blood samples collected from 171 Thai and 248 Myanmese patients attending a malaria clinic in Ranong province, Thailand, located near the Myanmar border were investigated for P. knowlesi using nested PCR assays. Positive samples were also investigated by PCR for Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium ovale, and were confirmed by sequencing the gene encoding the circumsporozoite protein (csp). RESULTS: Two samples, one obtained from a Thai and the other a Myanmese, were positive for P. knowlesi only. Nucleotide sequences of the csp gene derived from these two patients were identical and phylogenetically indistinguishable from other P. knowlesi sequences derived from monkeys and humans. Both patients worked in Koh Song, located in the Kawthoung district of Myanmar, which borders Thailand. CONCLUSION: This study indicates that transmission of P. knowlesi is occurring in the Ranong province of Thailand or the Kawthoung district of Myanmar. Further studies are required to assess the incidence of knowlesi malaria and whether macaques in these areas are the source of the infections. PMID- 22313519 TI - A case-control study on the association between chronic prostatitis/chronic pelvic pain syndrome and erectile dysfunction. AB - What's known on the subject? and What does the study add? In recent years, a number of studies have reported a high prevalence of erectile dysfunction (ED) among patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Several studies have reported that the prevalence of ED ranges from 15.0 to 40.5% in men in China with CP/CPPS; however, the previous studies focusing on the prevalence of ED among patients with CP/CPPS all neglected to explore the magnitude of this association. Our study found an association between ED and previously diagnosed CP/CPPS. The odds of previous CP/CPPS were 3.62 times greater for cases than for controls, after adjusting for patient socio demographic characteristics, comorbidities, obesity, and alcohol abuse/alcohol dependence syndrome. OBJECTIVE: To examine the association between erectile dysfunction (ED) and a previous diagnosis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using a population-based dataset. PATIENTS AND METHODS: The data for this case-control study was obtained from the National Health Insurance database. A total of 3194 males, who were >=18 years of age when they first received a diagnosis of ED, were identified and 15 970 controls were randomly selected. The prevalence and risk of CP/CPPS among cases and controls were calculated by using conditional logistic regression analysis. RESULTS: In total, 667 (3.5%) of the 19 164 sampled subjects had been diagnosed with CP/CPPS before the index date; CP/CPPS was found in 276 (8.6%) cases and in 391 (2.5%) controls (P < 0.001). Regression analysis indicated that cases were more likely to have had previous CP/CPPS (odd ratio 3.62, 95% confidence interval 3.07-4.26) after adjusting for patient monthly income, geographical location and urbanization level, as well as hypertension, diabetes, coronary heart disease, renal disease, obesity and alcohol abuse/alcohol dependence syndrome status, when compared with controls. CONCLUSIONS: We conclude that there was an association between ED and having been previously diagnosed with CP/CPPS. Urologists should be alert to the association between CP/CPPS and ED, and assess the erectile function of patients suffering from CP/CPPS. PMID- 22313520 TI - The influence of health education on the prevalence of intestinal parasites in a low-income community of Campos dos Goytacazes, Rio de Janeiro State, Brazil. AB - In a recent study by our group on the prevalence of intestinal parasitic infections and on the knowledge, attitudes and practices of local residents of Campos dos Goytacazes, Rio de Janeiro, Brazil, we observed that about 50% of the inhabitants were parasitized and had some knowledge of intestinal parasitic infections but did not apply this knowledge in daily practice. We were thus motivated to implement strategies in health education to promote preventive measures in the locality. The goal of the present work was to evaluate the influence of health education on the prevalence of intestinal parasitic infections in the region in an effort to strengthen public policies for controlling these diseases in Brazil. The methodology adopted was based on action research and a theoretical framework of health promotion. Our results demonstrate that the study population exhibited an enhanced awareness of the importance of disease from intestinal parasitic infections. Attitudes and practices related to prevention were significantly improved after the shared health education. In conclusion, this study allowed the shared construction of knowledge that reflected the true needs of the residents. PMID- 22313521 TI - Alterations in the fat body cells of Rhinocricus padbergi (Diplopoda) resulting from exposure to substrate containing sewage sludge. AB - The final disposal of residues generated at sewage treatment plants (STPs) has become a major problem for cities, due to the increase in the amount of treated sewage. One of the alternatives for the residue, labeled "sewage sludge," is its reuse in agriculture and in degraded soil. However, not all pathogens and metals present in it are eliminated during treatment. Diplopods have been used as bioindicators in ecotoxicological tests as they are constantly in close contact with the soil. Owing to this fact, the purpose of this study was to expose specimens of the diplopod Rhinocricus padbergi to substrate containing sewage sludge collected at STPs to analyze morphological alterations in their parietal and perivisceral fat body, where substances are stored. The exposures were held for 7, 15, or 90 days at different concentrations of sewage sludge (control, 1%, 10%, and 50%). The parietal fat body showed no alterations in any of the three exposure periods or concentrations. Alterations in the perivisceral fat body were observed for all exposure periods. According to the results, we suggest that the sludge used has toxic agents responsible for changing the animal's perivisceral fat body. PMID- 22313522 TI - The effect of lutein- and zeaxanthin-rich foods v. supplements on macular pigment level and serological markers of endothelial activation, inflammation and oxidation: pilot studies in healthy volunteers. AB - The aim of the present study was to compare the effect of lutein- and zeaxanthin rich foods and supplements on macular pigment level (MPL) and serological markers of endothelial activation, inflammation and oxidation in healthy volunteers. We conducted two 8-week intervention studies. Study 1 (n 52) subjects were randomised to receive either carrot juice (a carotene-rich food) or spinach powder (a lutein- and zeaxanthin-rich food) for 8 weeks. Study 2 subjects (n 75) received supplements containing lutein and zeaxanthin, beta-carotene, or placebo for 8 weeks in a randomised, double-blind, placebo-controlled trial. MPL, serum concentrations of lipid-soluble antioxidants, inter-cellular adhesion molecule 1, vascular cell adhesion molecule 1, C-reactive protein and F2-isoprostane levels were assessed at baseline and post-intervention in both studies. In these intervention studies, no effects on MPL or markers of endothelial activation, inflammation or oxidation were observed. However, the change in serum lutein and zeaxanthin was associated or tended to be associated with the change in MPL in those receiving lutein- and zeaxanthin-rich foods (lutein r 0.40, P = 0.05; zeaxanthin r 0.30, P = 0.14) or the lutein and zeaxanthin supplement (lutein r 0.43, P = 0.03; zeaxanthin r 0.22, P = 0.28). In both studies, the change in MPL was associated with baseline MPL (food study r - 0.54, P < 0.001; supplement study r - 0.40, P < 0.001). We conclude that this 8-week supplementation with lutein and zeaxanthin, whether as foods or as supplements, had no significant effect on MPL or serological markers of endothelial activation, inflammation and oxidation in healthy volunteers, but may improve MPL in the highest serum responders and in those with initially low MPL. PMID- 22313523 TI - Healing process of venous ulcers: the role of microcirculation. AB - In order to describe adequately the process of healing in the intermediate degrees, we investigated microcirculatory changes in the venous ulcers at well defined stages of wound repair. We investigated dynamic changes in microcirculation during the healing process of venous ulcers. Ten venous ulcers were investigated in three consecutive clinical stages of wound healing: non granulation tissue (NGTA), GTA and scar. Subpapillary microcirculation was measured by laser Doppler perfusion (LDP) imaging and expressed using LDP values in arbitrary units. Nutritive perfusion by capillary microscopy and expressed as capillary density (CD) - the number of capillaries per square millimetre. Before the development of GTA the LDP was low (median 1.35; lower-upper quartiles 0.71 1.83) accompanied with zero CD in all but one patient who had a density of 1. With the first appearance of GTA in the same area, the LDP was improved (2.22; 1.12-2.33; P = 0.0024) when compared with NGTA, in combination with a significant increase in CD (1.75; 0-3; P = 0.0054). In scar, the LDP was similar to that in the NGTA (1.03; 0.77-1.83; P = 0.278), combined with the highest CD (5.75; 4.5-8) in comparison with the previous stages of the area (for both pairs, P < 0.0001). Venous ulcers are caused by poor nutritive and subpapillary perfusion. Subpapillary perfusion plays a major role in the formation of GTA. In a scar, the increased nutritive perfusion is sufficient to cover the blood supply and keep skin viable while subpapillary perfusion is low. PMID- 22313524 TI - A novel Acetyl-CoA synthetase short-chain subfamily member 1 (Acss1) gene indicates a dynamic history of paralogue retention and loss in vertebrates. AB - Acetyl-CoA short chain synthetases (ACSSs) are key enzymes in the activation of fatty acids through the formation of thioesters with CoA. Three subfamily members are currently recognized in the human genome, ACSS1, ACSS2 and ACSS3, all single copy genes. The mitochondrial isoform, Acss1, plays a key role in the metabolism of acetate for energy production. While the single copy condition has been accurately established in humans, the evolutionary history of the Acss1 subfamily in vertebrates has yet to be elucidated, in particular, the isoform diversity, origin and function. Through genome database mining we analyzed the diversity of Acss1 isoforms in vertebrate classes. We detected the presence of a novel Acss1 isoform, which we name Acss1B. This new gene, Acss1B, has a curious phylogenetic distribution being found in teleosts (except zebrafish), sauropsids (birds and reptiles) and probably chondrichthyes. In contrast Acss1A is found in all the investigated species, except the teleost medaka. By means of comparative genomics and phylogenetics we show that Acss1A and Acss1B were generated in the quadruplication of the vertebrate genome. In effect, we find that amphioxus, a pre-genome duplication chordate, has a single Acss1 gene in a genomic region equally related to a quadrupled vertebrate genomic set. Consequently, Acss1B has been lost in some teleosts, amphibians and mammals, while Acss1A is probably absent in medaka. The reported findings illustrate an especially dynamic pattern of paralogue retention and independent loss in vertebrate species involving the Acss1 subfamily, whose functional consequences in energy metabolism are as yet unknown. PMID- 22313525 TI - Deep sequencing analysis of small non-coding RNAs reveals the diversity of microRNAs and piRNAs in the human epididymis. AB - The epididymis plays a crucial role in regulating the development of sperm motility and fertilizing capacity. Small non-coding RNAs (sncRNAs), especially microRNAs (miRNAs), can participate in the regulation of various physiological pathways. However, their abundance and whether they are involved in the regulation of gene expression in the human epididymis are unknown. By adopting the Solexa deep sequencing approach, we systematically investigated the sncRNAs in the adult human epididymis. A total of 4903 unique sequences representing 527 known miRNA were discovered. Eighteen novel miRNA genes encoding 23 mature miRNAs were also identified and the expression of some of them was confirmed by qRT-PCR. The presence of Piwi-interacting RNAs (piRNAs) in the library also adds to the diversity of the sncRNA population in the human epididymis. This research will contribute to a preliminary database for their functional study in male reproductive system. PMID- 22313526 TI - Polymorphisms of glutathione S-transferases M1, T1, P1 and A1 genes in the Tunisian population: an intra and interethnic comparative approach. AB - Genetic polymorphisms in glutathione S-transferases (GSTs) genes might influence the detoxification activities of the enzymes predisposing individuals to cancer risk. Owing to the presence of these genetic variants, inter-individual and ethnic differences in GSTs detoxification capacity have been observed in various populations. Therefore, the present study was performed to determine the prevalence GSTM1 0/0, GSTT1 0/0, GSTP1 Ile(105)Val, and GSTA1 A/B polymorphisms in 154 healthy individuals from South Tunisia, and to compare them with those observed in North and Centre Tunisian populations and other ethnic groups. GSTM1 and GSTT1 polymorphisms were analyzed by a Multiplex-PCR approach, whereas GSTP1 and GSTA1 polymorphisms were examined by PCR-RFLP. The frequencies of GSTM10/0 and GSTT1 0/0 genotypes were 53.9% and 27.9%, respectively. The genotype distribution of GSTP1 was 47.4% (Ile/Ile), 40.9% (Ile/Val), and 11.7% (Val/Val). For GSTA1, the genotype distribution was 24.7% (A/A), 53.9% (A/B), and 21.4% (B/B). The combined genotypes distribution of GSTM1, GSTT1, GSTP1 and GSTA1 polymorphisms showed that thirty one of the 36 possible genotypes were present in our population; eight of them have a frequency greater than 5%. To the best of our knowledge, this is the first report of GSTs polymorphisms in South Tunisian population. Our findings demonstrate the impact of ethnicity and reveal a characteristic pattern for Tunisian population. The molecular studies in these enzymes provide basis for further epidemiological investigations in the population where these functional polymorphisms alter therapeutic response and act as susceptibility markers for various clinical conditions. PMID- 22313527 TI - Block of Na+ currents and suppression of action potentials in embryonic rat dorsal root ganglion neurons by ranolazine. AB - Ranolazine, an anti-anginal drug, reduces neuropathic and inflammatory-induced allodynia in rats. However, the mechanism of ranolazin's anti-allodynic effect is not known. We hypothesized that ranolazine would reduce dorsal root ganglion (DRG) Na(+) current (I(Na)) and neuronal firing by stabilizing Na(+) channels in inactivated states to cause voltage- and frequency-dependent block. Therefore, we investigated the effects of ranolazine on tetrodotoxin-sensitive (TTXs) and tetrodotoxin-resistant (TTXr) I(Na) and action potential parameters of small diameter DRG neurons from embryonic rats. Ranolazine (10 and 30 MUM) significantly reduced the firing frequency of evoked action potentials in DRG neurons from 19.2 +/- 1.4 to 9.8 +/- 2.7 (10 MUM) and 5.7 +/- 1.3 (30 MUM) Hz at a resting membrane potential of -40 mV. Ranolazine blocked TTXs and TTXr in a voltage- and frequency-dependent manner. Furthermore, ranolazine (10 MUM) blocked hNa(v)1.3 (expressed in HEK293 cells) and caused a hyperpolarizing shift in the voltage dependence of steady-state intermediate and slow inactivation Na(v)1.3 current. Taken together, the results suggest that ranolazine suppresses the hyperexcitability of DRG neurons by interacting with the inactivated states of Na(+) channels and these actions may contribute to its anti-allodynic effect in animal models of neuropathic pain. PMID- 22313528 TI - CNS regulation of appetite. AB - This article reviews the regulation of appetite from a biopsychological perspective. It considers psychological experiences and peripheral nutritional systems (both episodic and tonic) and addresses their relationship with the CNS networks that process and integrate their input. Whilst such regulatory aspects of obesity focus on homeostatic control mechanisms, in the modern environment hedonic aspects of appetite are also critical. Enhanced knowledge of the complexity of appetite regulation and the mechanisms that sustain obesity indicate the challenge presented by management of the obesity epidemic. Nonetheless, effective control of appetite expression remains a critical therapeutic target for weight management. Currently, strategies which utilise a combination of agents to target both homeostatic and hedonic control mechanisms represent the most promising approaches. This article is part of a Special Issue entitled 'Central Control of Food Intake'. PMID- 22313529 TI - What is the prognosis for new centrally-acting anti-obesity drugs? AB - Obesity is a global problem that is predominantly caused by the increasing adoption of a low-cost, Westernised diet that is rich in fat and sugar and a more sedentary lifestyle. The costs of this epidemic are substantial increases in Type 2 diabetes, cardiovascular disease and some types of cancer that are certain to place a huge burden on individuals, healthcare providers and society. In this review, we provide an overview of the chequered history of pharmacotherapy for the treatment of obesity and an analysis of the regulatory and commercial challenges for developing new centrally-acting drugs in this metabolic indication. The efficacy and safety of the drug candidates that are currently at the pre-registration phase, i.e., lorcaserin, Qnexa and Contrave, are critically assessed. The main focus, however, is to provide a comprehensive review of the wide range of novel CNS compounds that are in the discovery phase or early clinical development. The profiles of various clinical candidates in animal models of obesity predict that several new CNS approaches in the clinic have the potential to deliver greater weight-loss than existing agents. This article is part of a Special Issue entitled 'Central Control of Food Intake'. PMID- 22313530 TI - CNS distribution of metabotropic glutamate 2 and 3 receptors: transgenic mice and [3H]LY459477 autoradiography. AB - Group II metabotropic glutamate (mGlu) receptor agonists were efficacious in randomized clinical research trials for schizophrenia and generalized anxiety disorder. The regional quantification of mGlu(2) and mGlu(3) receptors remains unknown. A selective and structurally novel mGlu(2/3) receptor agonist, 2-amino-4 fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY459477) was tritiated and the distribution of mGlu(2) and mGlu(3) receptors was studied in transgenic mice lacking either mGlu(2), mGlu(3) or both receptors. LY459477 is an agonist with 1 2 nM potency for rodent and human mGlu(2) and mGlu(3) receptors. The functional selectivity of LY459477 was demonstrated by over 640-fold selectivity and the displacement binding selectivity was greater than 320-fold for all glutamate receptors except mGlu(6) (~230-fold). More than 1000-fold selectivity was demonstrated for all non-glutamate receptors known to be targeted by antipsychotic drugs. Like atypical antipsychotic drugs, LY459477 reversed in vitro electrophysiological effects of a serotonergic hallucinogen and behavioral effects of phencyclidine or amphetamine. There was virtually no binding of [(3)H]LY459477 to any brain region in mice with a deletion of both mGlu(2) and mGlu(3) receptors. Regions enriched in mGlu(2) receptors included the medial prefrontal cortex, select hippocampal regions, the medial mammillary nucleus, the medial habenula, and the cerebellar granular cell layer. Regions enriched in mGlu(3) receptors were the dorsolateral entorhinal cortex, the hippocampal CA1 field, the piriform cortex, the substantia nigra, the thalamic reticular nucleus, and primary sensory thalamic nuclei. These findings suggest [(3)H]LY459477 should be a useful tool to further define the role of mGlu(2) and mGlu(3) receptors throughout the brain with respect to major neuropsychiatric syndromes. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. PMID- 22313531 TI - The cost of blood transfusion in Western Europe as estimated from six studies. AB - BACKGROUND: Blood is a costly and scarce resource. We report on a systematic review of the literature to estimate the cost of a 2-unit red blood cell (RBC) transfusion in Western Europe. STUDY DESIGN AND METHODS: Medline was searched for studies about the cost of RBC transfusion in Europe. Data extracted included authors, country, year of data, cost perspective, cost types, cost elements, units examined, study design, study population, and cost of a 2-unit blood transfusion. The population-weighted mean cost per 2 units of transfused blood was calculated. RESULTS: Six studies met inclusion and exclusion criteria and reported data from the United Kingdom, Sweden, Switzerland, Austria, and France. Methodology used to derive cost estimates differed across the studies. The population-weighted mean cost of transfusing 2 units of blood was ? 877.69. CONCLUSION: The estimated cost of transfusing 2 units of RBCs in Western Europe is significant. Differences in methodology were partially diffused by aggregation of prior estimates into a population-weighted mean. Future cost studies should follow the Cost of Blood Consensus Conference (COBCON) recommendation to apply activity-based costing methods. PMID- 22313532 TI - Stem cells in human normal endometrium and endometrial cancer cells: characterization of side population cells. AB - Recently, adult stem cells have been identified in several mature tissues. The human endometrium is responsive to sex steroid hormone. It undergoes extraordinary growth in a cyclic manner and is shed and regenerated throughout a woman's lifetime. It has been proposed that the human endometrium may contain a population of stem cells, which are responsible for its remarkable regenerative ability. It is also suggested that stem-like cells exist in cancer tissues. Stem like cell subpopulations, referred to as "side population" (SP) cells, have been identified in several tissues and tumors based on their ability to efflux the fluorescent dye Hoechst 33342. Recently, we isolated and characterized the SP cells in normal human endometrium and in an endometrial cancer (EC) cell line. Endometrial SP cells can function as progenitor cells. EC SP cells show the following: (1) reductions in the expression levels of differentiation markers; (2) long-term repopulating properties; (3) self-renewal capacity; (4) enhancement of migration and podia formation; (5) enhancement of tumorigenicity; and (6) bipotent developmental potential (tumor cells and stroma-like cells), suggesting that these SP cells have cancer stem-like cell features. We review the articles that show the presence of stem cells in normal endometrium and EC cells and demonstrate the results of our studies. PMID- 22313533 TI - Effect of the endothelin receptor antagonist tezosentan on alpha-naphthylthiourea induced lung injury in rats. AB - Acute lung injury is an inflammatory syndrome that increases the permeability of the blood-gas barrier, resulting in high morbidity and mortality. Despite intensive research, treatment options remain limited. We investigated the protective efficacy of tezosentan, a novel, dual endothelin receptor antagonist, in an experimental model of alpha-naphthylthiourea (ANTU)-induced acute lung injury in rats. ANTU was intraperitoneally (i.p.) injected into rats at a dose of 10 mg/kg. Tezosentan was injected 30 minutes before ANTU was subcutaneously (s.c.) injected at doses of 2, 10, or 30 mg/kg, 60 minutes before ANTU was injected at doses of 2, 10, or 30 mg/kg (i.p.), and 90 minutes before ANTU at a dose of 10 mg/kg (i.p.). Four hours later, the lung weight/body weight (LW/BW) ratio and pleural effusion (PE) were measured. When injected 30 minutes before ANTU at doses of 2, 10, or 30 mg/kg (s.c.), tezosentan had no effect on lung pathology. When injected 60 minutes before ANTU at doses of 2, 10, or 30 mg/kg (i.p.) or 90 minutes before ANTU (10 mg/kg, i.p.), tezosentan significantly decreased the PE/BW ratio and had a prophylactic effect on PE formation at all doses. Therefore, tezosentan may attenuate lung injury. Furthermore, its acute and inhibitory effects on fluid accumulation were more effective in the pleural cavity than in the interstitial compartment in this experimental model. PMID- 22313534 TI - Essentiality of HIV testing and education for effective HIV control in the national pilot harm reduction program: the Taiwan experience. AB - In 2005, a national pilot harm reduction program (PHRP), which mainly included a methadone maintenance treatment program (MMTP) and a needle/syringe exchange program (NSP), was implemented in Taiwan. We conducted this study to evaluate the effectiveness of harm reduction measures on HIV control among injecting drug users (IDUs) between PHRP and nonPHRP. The data on HIV, collected from incumbent Taiwanese authorities, were analyzed for their associations, risk and protective factors with PHRP measures. While the monthly HIV incidences did not show significant differences before and after PHRP in the four areas with PHRP (Taipei City, Taipei County, Taoyuan County and Tainan County), a significant increase in the HIV incidence was found in the 21 areas without PHRP. Hence, the implementation of the PHRP did result in a significant difference in the monthly HIV incidence between areas with and without the PHRP. Mandatory HIV testing was significantly associated with the HIV incidence according to the generalized estimation equations (GEE) model. With adjustments of time period and area with PHRP, and urban area, protective factors associated with HIV incidence were: educational materials, condoms, dilution water, and alcohol sponges/swabs. MMTP contributed to a higher HIV incidence, probably due to the concurrent HIV testing upon admission. Since HIV testing was not required in the NSP, the HIV testing dependent MMTP may explain the association of the PHRP intervention and an increased HIV incidence. In summary, HIV testing and education were essential for effective HIV control upon implementing the PHRP. PMID- 22313535 TI - Antinuclear antibody titer and treatment response to peginterferon plus ribavirin for chronic hepatitis C patients. AB - Positive serum antinuclear antibody (ANA) is not infrequent in chronic hepatitis C virus (HCV)-infected patients. This prospective study evaluated the impact of ANA on the response to and safety of peginterferon/ribavirin combination therapy for chronic hepatitis C patients in clinical practice. We enrolled 243 consecutive patients who were treated with a 24-week regimen of peginterferon alpha plus ribavirin, with a 24-week follow-up period. ANA titer was determined before antiviral treatment. The primary end-point was sustained virological response (SVR), defined as HCV RNA <50 IU/mL throughout the follow-up period. Overall, 187 (77.0%) patients experienced a SVR. In the 105-patient HCV genotype non-1 group, patients with ANA titer >=1:80 had a significantly lower SVR rate than those with ANA titer <1:80 (67.7% vs. 95.8%, respectively, p = 0.013). In contrast, in the 138-patient HCV genotype 1 group, the SVR rate did not differ between patients with and without ANA titer >=1:80. Multivariate regressive analyses showed that ANA >=1:80, age and HCV RNA levels were independent factors associated with SVR in HCV genotype non-1 patients; whereas HCV RNA levels and hepatic fibrosis were prognostic predictors of SVR in HCV genotype 1 patients. The frequencies of adverse events were similar between patients with and without ANA seropositivity. Peginterferon/ribavirin combination therapy is effective and safe in ANA-positive chronic hepatitis C patients. A high ANA titer was a negative prognostic factor for treatment response in HCV genotype non-1 patients. PMID- 22313536 TI - The importance of measuring macroprolactin in the differential diagnosis of hyperprolactinemic patients. AB - This study investigated the differences in clinical and laboratory features as well as treatment response in 70 outpatients with macroprolactinemia and monomeric hyperprolactinemia treated with dopamine agonists. After precipitation of the patients' serum samples with poly-ethylene-glycol (PEG), serum prolactin (PRL) levels were measured. We also measured serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol for women and testosterone for men. Clinical symptoms and signs were recorded. All patients received brain magnetic resonance imaging (MRI). After excluding patients with macroadenoma, 66 patients were treated with the dopamine agonist cabergoline. After 1 year, the clinical responses to cabergoline were recorded and PRL levels measured. Of the initial 70 patients with hyperprolactinemia, 15 patients (21.4%) were found to have macroprolactinemia, while the rest had monomeric hyperprolactinemia. The two groups did not differ with regard to galactorrhea, menstrual disturbances or impotence. There were no significant group differences in serum LH, FSH, estradiol or testosterone levels. Patients with macroprolactinemia, however, had a significantly lower infertility rate than those with true hyperprolactinemia (6.7% vs. 32.7%, p=0.005). A greater percentage of macroprolactinemic patients had normal MRI pituitary images than those with hyperprolactinemia (73.3% vs. 34.5%, p=0.029). Compared to those with true hyperprolactinemia, patients with macroprolactinemia were found to have no significant changes in clinical features and PRL levels after 1 year of cabergoline therapy (after PEG precipitation, pre- and post-PRL levels: 59.3 +/- 100.2 to 13.8 +/- 9.5 ng/mL vs. 6.1 +/- 5.3 to 5.1 +/- 4.3 ng/mL, p=0.002). In conclusion, while macroprolactinemia is a common cause of hyperprolactinemia, many clinical and laboratory features cannot be used reliably to differentiate macroprolactinemia from true hyperprolactinemia. Routine screening for all hyperprolactinemic sera with PEG might prevent the unnecessary use of image studies and medical treatments for people with hyperprolactinemia. PMID- 22313537 TI - Minimal invasive pyeloplasty technique with vertical surgical approach: an alternative to laparoscopic pyeloplasty. AB - This retrospective clinical study presents pyeloplasty results following a muscle splitting dissection, with mini-flank incision, using instruments held in a vertical position. Between 2004 and 2010, dismembered pyeloplasty (Anderson Hynes) was performed in 37 cases (32 males and 5 females) with an average age of 26 years (range, 20-56 years). The technique was carried out through a window opened by separating the lateral abdominal muscles. Operation duration, length of incision, postoperative pain, complications, and radiological and clinical results were discussed. The operation duration was between 50 and 90 minutes (average=65 minutes), the incisional length 5 and 7 cm (average=5.2 cm), and visual pain scale was 4.1 +/- 3.1 and 3.3 +/- 3.4 at 4 and 24 hours after the operation, respectively. The duration of hospitalization was between 30 and 120 hours (average=42 hours). In a retrospective analysis of our study, one case was reoperated on, following recurrence with obstruction, there were 9 cases with prolonged dilation in response to diuretics and 29 cases with complete recovery. Pyeloplasty operations, with a vertical surgical approach through smaller incisions and muscle separation, offered shorter periods of hospitalization, less postoperative pain, acceptable cosmetic results and higher rates of functional recovery. PMID- 22313538 TI - Effects of individual resilience intervention on indigenous people who experienced Typhoon Morkot in Taiwan. AB - In 2009, Typhoon Morakot struck Taiwan and caused serious harm to the indigenous peoples living in the southern mountainous regions. The objective of this study is to examine the effects of and the factors involved in individual resilience intervention of typhoon victims. Quantitative research was performed from October 2009 through September 2010. Purposive sampling yielded 77 indigenous persons who were willing to serve as participants in this study. These participants all maintained legal or actual residence in the areas of Kaohsiung that were affected by the typhoon. An individual resilience intervention program was implemented. The findings show the following: (1) after completing the individual resilience intervention program, the participants had higher individual resilience scores than before participating in the intervention program; and (2) individual resilience scores were significantly affected by residency after the typhoon. These findings suggest that an individual resilience intervention program is a useful approach that can be used to enhance the individual resilience of a victim and that professionals should pay more attention to victims who have to leave their hometowns after disasters. PMID- 22313539 TI - Enterococcus hirae-related acute pyelonephritis and cholangitis with bacteremia: an unusual infection in humans. AB - Very few reports are available from the literature related to Enterococcus hirae infection in humans, which is more frequently seen in animals and birds. We report two patients with E hirae bacteremia caused by acute pyelonephritis and acute cholangitis. The clinical courses have been smooth on use of sensitive antibiotic therapy. In both cases, the primary sources and portals of entry are clearly identified. PMID- 22313540 TI - Primary small cell carcinoma of the lesser omentum. AB - Although pulmonary small cell carcinoma (SCC) is seen frequently, SCC that originates from the extrapulmonary organs is extremely rare. We herein report a case of a SCC located in the lesser omentum. A 61-year-old male was admitted to our department due to intermittent epigastralgia for 2 months. Ultrasonography (US) revealed an irregular hypoechoic mass measuring about 58 mm * 50 mm * 45 mm under the left lobe of the liver. Magnetic resonance imaging (MRI) was performed to verify the irregular mass with T1- and T2- weighted images between the left lobe of liver and the stomach. At laparotomy, the well-circumscribed neoplasm was found in the lesser omentum, and the fundus of the neoplasm was located in the root of left gastric artery. Intraoperative microscopic evaluation of frozen sections revealed malignancy of the lesser omentum. Resection of the neoplasm was performed, and the combined resection of the vagal nerve was also performed for the partial adhesion. Pyloroplasty was performed for avoiding delayed gastric emptying caused by combined resection of vagal nerve. The lymph nodes dissection at lesser curvature and right cardia was also performed with a negative result. Based on the histological findings, the final diagnosis of primary lesser omental SCC was confirmed. The pathologic staging showed locoregional disease. PMID- 22313541 TI - Jejunal undifferentiated spindle cell sarcoma with glossal metastasis. PMID- 22313542 TI - An examination of the dynamic changes in prostate-specific antigen occurring in a population-based cohort of men over time. PMID- 22313543 TI - Comparison of forces applied to the maxillary incisors by direct and indirect laryngoscopes. PMID- 22313544 TI - Gene expression profiling and pathway analysis identify the integrin signaling pathway to be altered by IL-1beta in human pancreatic cancer cells: role of JNK. AB - The pro-inflammatory cytokine, IL-1beta, is a critical component of the persistent inflammatory milieu that pancreatic cancer cells frequently encounter. Although several studies report diverse mechanisms responsible for this association, yet a comprehensive global analysis of the effect of IL-1beta in these cells is not clearly evident. In this study, we performed whole genome transcriptome analysis of control and IL-1beta treated human pancreatic MIA PaCa 2 cells, validated the most targeted pathway and evaluated the role of JNK therein. 225 Genes were up-regulated and 1215 were down-regulated and these were categorized into biological processes and cellular pathways using the PANTHER classification system. The altered genes categorized into significant biological processes that included those of cell cycle, mitosis, transport and intracellular protein trafficking. The integrin signaling pathway emerged as harboring the maximum number of differentially expressed genes. Two important genes of this pathway, namely vinculin and alpha5-integrin were validated and both depicted significant inhibition by IL-1beta that was prevented in the presence of JNK siRNA. In a wound healing assay, IL-1beta increased the migratory rate of MIA PaCa-2 and Panc-1 cells that was abrogated by JNK inhibition. Additionally, vinculin and alpha-integrin siRNAs also increased the migration of these cells along the wound edge. These results suggest that in these pancreatic cancer cells, IL-1beta inhibits components of the integrin signaling pathway in a JNK dependent manner that contributes to their increased migratory potential. Therefore, JNK might be potentially targeted to prevent the migration and invasion of pancreatic cancer cells. PMID- 22313545 TI - Opsin3 sensitizes hepatocellular carcinoma cells to 5-fluorouracil treatment by regulating the apoptotic pathway. AB - Hepatocellular carcinoma (HCC) is the third most common cancer worldwide, causing over 0.5 million deaths per year, with approximately half of these in China. Chemotherapy is the optimal treatment for patients with advanced HCC, although chemoresistance has become a significant obstacle to successful anti-cancer therapy. The expression of opsin3 (OPN3), also called encephalopsin or panopsin, is lower in 5-fluorouracil (5-FU)-resistant Bel7402(5-FU) cells compared to 5-FU sensitive Bel7402 cells. To explore the role of OPN3 in 5-FU resistance, OPN3 overexpressing (Bel7402(5-FU)-OPN3) and knockdown (Bel7402-RNAi-OPN3) cell lines were generated. Bel7402(5-FU)-OPN3 cells were more sensitive to 5-FU treatment than controls, while OPN3 knockdown resulted in a significant increase in 5-FU resistance. This result was replicated in a second HCC cell line, HepG2. Further investigation of the mechanism revealed that decreased OPN3 levels in Bel7402(5 FU) cells activated the anti-apoptotic pathway through increasing phospho-Akt and the Bcl2/Bax ratio, while overexpression of OPN3 inactivated this pathway. Taken together, these results suggest that OPN3 depletion is involved in 5-FU resistance, and that therapeutic strategies targeting OPN3 may improve HCC sensitivity to chemotherapy. PMID- 22313546 TI - Penile Doppler sonographic and clinical characteristics in Peyronie's disease and/or erectile dysfunction: an analysis of 1500 men with male sexual dysfunction. AB - What's known on the subject? and What does the study add? Penile colour Doppler ultrasonography (CDU) can be an invaluable investigative tool to characterize penile abnormalities to complement clinical history and physical examination in the evaluation of men with Peyronie's disease (PD) and/or erectile dysfunction (ED). Although CDU findings between men with PD and those with ED were not markedly different, subtle differences were observed. The classic penile CDU findings in men with PD comprise tunical thickening, intracavernosal fibrosis, septal fibrosis and intracavernosal calcification, while, in men with ED, low peak systolic velocity and high end-diastolic velocity are found on penile haemodynamics. Previously published studies have focused predominantly on either ED or PD exclusively, or examine the risk of progression to ED in the PD population. To our knowledge, this is the largest and most comprehensive analysis of penile CDU and clinical findings in men with PD and/or ED. The large sample size and multivariable analysis allow meaningful interpretation of the results. This study has found some substantial differences in the penile CDU findings of men with PD and/or ED that have not previously been reported. Although the risk factors of ED may be greater than those for PD, there is crossover in age, cardiovascular risk factors, trauma and penile CDU findings in men with PD and/or ED. OBJECTIVE: To explore the differences in penile colour Doppler ultrasonography (CDU) findings between men with Peyronie's disease (PD) and those with erectile dysfunction (ED). MATERIALS AND METHODS: Patients presenting with PD and/or ED who underwent penile CDU were recruited to the study. Patient demographics, comorbidities, International Index of Erectile Function-5 scores, previous therapies and physical findings were documented. Penile curvature, presence of tunical thickening, septal fibrosis, intracavernosal fibrosis and calcification, and cavernosal vascular status were recorded. RESULTS: A total of 1500 men underwent penile CDU during the 10-year period. Of these men, 891 men presented with PD and 609 men had ED only. Men with ED had higher rates of diabetes and coronary artery disease (P < 0.05). Isolated tunical thickening was more common in older men and in the PD cohort. The presence of intracavernosal fibrosis correlated strongly with difficulty maintaining erection (P < 0.05). Impaired cavernosal arterial flow was observed in men with decrease penile rigidity and penile pain, while higher end-diastolic velocities were found in men with difficulty maintaining erection and tunical thickening on penile CDU. CONCLUSIONS: Men with PD and ED had many similarities and differences on penile CDU. Penile CDU continues to be an invaluable clinical tool in the management of men with male sexual dysfunction. PMID- 22313548 TI - Cost-effectiveness of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitor in the treatment of acute ST-segment elevation myocardial infarction. AB - OBJECTIVE: To assess the cost-effectiveness of bivalirudin versus heparin and glycoprotein IIb/IIIa inhibitor (H-GPI) in patients undergoing primary percutaneous coronary intervention (PPCI) for acute ST-segment elevation myocardial infarction (STEMI), from a UK health service perspective. DESIGN: Cost utility analysis with life-long time horizon. MAIN OUTCOME MEASURES: Costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness. METHODS: Event risks and medical resource use data derived from the HORIZONS-AMI trial were entered into a decision analytic model. Clinical events until the end of year 1 (main model) or year 3 (alternative model) were modelled in detail. Adjustments were applied to approximate UK routine practice characteristics. Life expectancy of 1-year or 3-year survivors, health-state utilities, initial hospitalisation length of stay in the comparator strategy and unit costs were based on UK sources. Costs and effects were discounted at 3.5%. RESULTS: The main model predicted bivalirudin and H-GPI patients to survive 11.52 and 11.35 (undiscounted) years on average, respectively, and to accrue 6.26 and 6.17 QALYs. Patient lifetime costs were L267 lower in the bivalirudin strategy (L12 843 vs L13 110). Extensive sensitivity and scenario analyses confirmed these results to be robust. In probabilistic analysis, quality-adjusted survival was higher and costs were lower with bivalirudin in 95.0% of simulation runs. In 99.2%, cost effectiveness was better than L20 000 per QALY gained. Results from the alternative model were fully consistent. CONCLUSION: The use of bivalirudin instead of H-GPI in STEMI patients undergoing PPCI is cost-effective, and offers a high probability of dominance. Background treatment with aspirin and clopidogrel is assumed. PMID- 22313549 TI - More than a meal... integrating non-feeding interactions into food webs. AB - Organisms eating each other are only one of many types of well documented and important interactions among species. Other such types include habitat modification, predator interference and facilitation. However, ecological network research has been typically limited to either pure food webs or to networks of only a few (<3) interaction types. The great diversity of non-trophic interactions observed in nature has been poorly addressed by ecologists and largely excluded from network theory. Herein, we propose a conceptual framework that organises this diversity into three main functional classes defined by how they modify specific parameters in a dynamic food web model. This approach provides a path forward for incorporating non-trophic interactions in traditional food web models and offers a new perspective on tackling ecological complexity that should stimulate both theoretical and empirical approaches to understanding the patterns and dynamics of diverse species interactions in nature. PMID- 22313547 TI - Addressing both depression and pain in late life: the methodology of the ADAPT study. AB - OBJECTIVE: To describe the methodology of the first NIH-funded clinical trial for seniors with comorbid depression and chronic low back pain. METHODS: Randomized controlled effectiveness trial using stepped care methodology. Participants are >=60 years old. Phase 1 (6 weeks) is open treatment with venlafaxine xr 150 mg/day and supportive management (SM). Response is 2 weeks of PHQ-9 <=5 and at least 30% improvement in the average numeric rating scale for pain. Nonresponders progress to phase 2 (14 weeks) in which they are randomized to high-dose venlafaxine xr (up to 300 mg/day) with problem solving therapy for depression and pain (PST-DP) or high-dose venlafaxine xr and continued SM. Primary outcomes are the univariate pain and depression response and both observed and self-reported disability. Survival analytic techniques will be used, and the clinical effect size will be estimated with the number needed to treat. We hypothesize that self efficacy for pain management will mediate response for subjects randomized to venlafaxine xr and PST-DP. RESULTS: Not applicable. CONCLUSIONS: The results of this trial will inform the care of these complex patients and further understanding of comorbid pain and depression in late life. PMID- 22313550 TI - QTc interval and its variability in patients with schizophrenia and healthy subjects: implications for a thorough QT study. AB - We compared heart rate-corrected QT interval (QTc) and its within- and between subject variability, in ECGs recorded several days apart for 207 patients with schizophrenia (age range 19-60 yr) with age- and gender-matched healthy controls. Patients had higher heart rates (mean+/-s.d.) than controls [75+/-15 beats per minute (bpm) vs. 63+/-10 bpm; p<0.0001]. QTc by Bazett's formula (QTcB) overestimated QTc interval at high heart rates; consequently QTcB was longer in patients (412+/-24 ms) than in controls (404+/-24 ms; p=0.0003). QTc by Fridericia's method (QTcF), which was not influenced by heart rate, was comparable (398+/-22 ms in patients vs. 401+/-19 ms in controls; p=0.17). Between subject variability in QTcF was similar in patients (17 ms) and controls (16.2 ms) but within-subject variability was larger (13.1 ms vs. 10 ms, respectively). Thus, a larger sample size is required when thorough QTc studies with a cross over design are performed in patients with schizophrenia than in healthy subjects; sample size is not increased for studies with a parallel design. Last, QTcF is preferred over QTcB in schizophrenia patients with higher heart rates. PMID- 22313552 TI - Rebalancing the major trauma computed tomography pan-scan between panacea and Pandora's Box. PMID- 22313551 TI - AIDS-orphanhood and caregiver HIV/AIDS sickness status: effects on psychological symptoms in South African youth. AB - OBJECTIVE: Research has established that AIDS-orphaned youth are at high risk of internalizing psychological distress. However, little is known about youth living with caregivers who are unwell with AIDS or youth simultaneously affected by AIDS orphanhood and caregiver AIDS sickness. METHODS: 1025 South African youth were interviewed in 2005 and followed up in 2009 (71% retention). Participants completed standardized measures of anxiety, depression, and posttraumatic stress. Comparison groups were youth who were AIDS-orphaned, other-orphaned, and nonorphaned, and those whose caregivers were sick with AIDS, sick with another disease, or healthy. RESULTS: Longitudinal analyses showed that both AIDS orphanhood and caregiver AIDS sickness predicted increased depression, anxiety, and posttraumatic stress symptoms over a 4-year period, independently of sociodemographic cofactors and of each other. Caregiver sickness or death by non AIDS causes, and having a healthy or living caregiver, did not predict youth symptomatology. Youths simultaneously affected by caregiver AIDS sickness and AIDS-orphanhood showed cumulative negative effects. CONCLUSIONS: Findings suggest that policy and interventions, currently focused on orphanhood, should include youth whose caregivers are unwell with AIDS. PMID- 22313553 TI - Practically speaking: emergency medicine and the palliative care movement. PMID- 22313554 TI - Review article: Crisis resource management in emergency medicine. AB - Effective team management is a core element of expert practice in emergency medicine. Thus far, training in emergency medicine has focussed predominantly on proficiency in medical and technical skills, with emergency physicians acquiring these 'non-technical' skills in an ad hoc manner or by trial and error with varying levels of success. This paper describes a set of behaviours that, when practised in conjunction with medical and technical expertise, can reduce the incidence of clinical error and contribute to effective teamwork and the smooth running of an ED. Teaching and practice of these behaviours is now a core element of training and skills maintenance in other high-risk areas, such as aviation, and is becoming part of the routine training for anaesthetists. They address areas, such as communication, leadership, knowledge of environment, anticipation and planning, obtaining timely assistance, attention allocation and workload distribution. We outline the application of these behaviours in the speciality of emergency medicine, and suggest that the teaching and practice of crisis resource management principles should become part of the curriculum for training and credentialing of emergency medicine specialists. PMID- 22313555 TI - Review article: Part one: Goal-directed resuscitation--which goals? Haemodynamic targets. AB - The use of appropriate resuscitation targets or end-points may facilitate early detection and appropriate management of shock. There is a fine balance between oxygen delivery and consumption, and when this is perturbed, an oxygen debt is generated. In this narrative review, we explore the value of global haemodynamic resuscitation end-points, including pulse rate, blood pressure, central venous pressure and mixed/central venous oxygen saturations. The evidence supporting the reliability of these parameters as end-points for guiding resuscitation and their potential limitations are evaluated. PMID- 22313556 TI - Emergency surgical cricothyroidotomy: 24 successful cases leading to a simple 'scalpel-finger-tube' method. AB - Surgical airway access justifiably remains the final option for managing the 'can't intubate can't ventilate' situation, but available techniques are often complicated and might require special equipment. This paper reports on the real world experience of two experienced Australian medical specialists with backgrounds in Anaesthesia and Aeromedical Retrieval who performed 24 surgical airways, mainly under adverse prehospital conditions, over a combined 40 years of practice. All attempts were successful, the majority through a simple open 'scalpel-finger-tube' method, which is described here. PMID- 22313557 TI - Critical illness in the emergency department: lessons learnt from the first 12 months of enrolments in the Critical Illness and Shock Study. PMID- 22313558 TI - Queensland Emergency Medicine Research Foundation: special report. AB - Development of any new profession is dependent on the development of a special body of knowledge that is the domain of the profession. Key to this is research. Following sustained lobbying, the Queensland Government agreed to establish an emergency medicine research fund as part of an Enterprise Bargaining Agreement in 2006. That fund is managed by the Queensland Emergency Medicine Research Foundation. The present article describes the strategic approaches of the Foundation in its first 3 years, the application of research funds, and foreshadows an evaluative framework for determining the strategic value of this investment. The Foundation has developed a range of personnel and project support funding programmes, and competition for funding has increased. Ongoing evaluation will seek to determine the effectiveness of the current funding strategy on improving the effectiveness of research performance. It will also evaluate the clinical and organizational outcomes. PMID- 22313559 TI - Comparison of radiation exposure of trauma patients from diagnostic radiology procedures before and after the introduction of a panscan protocol. AB - OBJECTIVES: To compare the proportion of patients exposed to a radiation dose in excess of 20 mSv, and to document missed injuries before and after the introduction of a panscan protocol for blunt trauma. METHODS: Data were collected retrospectively from our trauma database for 6 months before and after implementation of the protocol. All radiological studies performed during the initial patient assessment were identified. Radiation doses for each patient were calculated. Subgroup analyses were age <=30 and >30 years, injury severity score (ISS) <16 and >=16, and patient disposition as discharged from ED or admitted. RESULTS: There were 656 patients before and 624 after the introduction of the protocol. The proportion of patients exposed to a radiation dose >20 mSv increased by 8% (95% confidence interval [CI] 4-12), which equated to one extra person being exposed to >20 mSv for every 13 patients treated after the introduction of the protocol. The odds of receiving a radiation dose >20 mSv after the introduction of the protocol compared with the odds before were increased across all subgroups (<=30 years: odds ratio [OR] 2.7, 95% CI 1.3-5.8, P = 0.008; >30 years: OR 2.2, 95% CI 1.5-3.4, P < 0.001; ISS < 16: OR 2.4, 95% CI 1.5-3.9, P < 0.001; ISS >= 16: OR 2.0, 95% CI 1.0-3.7, P = 0.04; discharged home: OR 2.1, 95% CI 0.7-6.0, P = 0.17; admitted: OR 2.2, 95% CI 1.5-3.3, P < 0.001). There were six missed injuries before and four after. CONCLUSIONS: Introduction of a panscan protocol increased the proportion of trauma patients receiving a radiation dose >20 mSv. This increased risk occurred regardless of age or injury severity. PMID- 22313560 TI - Impact of polymerase chain reaction results on patient management during a viral meningitis outbreak in Tropical North Queensland. AB - OBJECTIVES: Enterovirus is the most commonly isolated pathogen in viral meningitis. We report on the first outbreak of viral meningitis in Tropical Queensland and the effect of polymerase chain reaction (PCR) results on antibiotic use and hospital length of stay. METHODS: Retrospective case series of consecutive patients presenting to the Townsville ED with viral meningitis were evaluated by examining hospital medical records. The study period was November 2008 to February 2009. RESULTS: Forty-three patients were available for full analysis of which 17 (40%) were female and 17 (40%) had a positive enteroviral PCR. Antibiotics were commenced on 37 (86%) of patients. There was no difference in hospital length of stay in patients with a negative versus positive PCR (2.52 vs 2.72 days, P = 0.68) or duration of antibiotic therapy (2.20 vs 1.94 days, P = 0.61). CONCLUSION: In our study a positive result on PCR was not associated with a shorter hospital length of stay or a shorter duration of antibiotic therapy. This contrasts with previous reports on this topic and requires further evaluation. PMID- 22313561 TI - Health reform: is routinely collected electronic information fit for purpose? AB - OBJECTIVE: Little has been reported about the completeness and accuracy of data in existing Australian clinical information systems. We examined the accuracy of the diagnoses of some chronic diseases in an ED information system (EDIS), a module of the NSW Health electronic medical record (EMR), and the consistency of the reports generated by the EMR. METHODS: A list of ED attendees and those admitted was generated from the EDIS, using specific (e.g. angina) and possible clinical terms (e.g. chest pain) for the selected chronic diseases. This EDIS list was validated with an audit of discharge summaries, and compared with a list generated, using similar specific and possible Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT), from the underlying EMR database. RESULTS: Of the 33,115 ED attendees, 2559 had diabetes mellitus (DM), cardiovascular disease or asthma/chronic obstructive pulmonary disease; of these 2559, 876 were admitted. Discharge summaries were missing for 12-15% of patients. Only three quarters or fewer of the diagnoses were confirmed by the discharge summary audit, best for DM and worst for cardiovascular disease. Proportion of agreement between the lists generated from the EDIS and EMR was best for DM and worst for asthma/chronic obstructive pulmonary disease. Possible reasons for this discrepancy are technical, such as use of different extraction terms or system inconsistency; or clinical, such as data entry, decision-making, professional behaviour and organizational performance. CONCLUSIONS: Variations in information quality and consistency of the EDIS/EMR raise concerns about the 'fitness for purpose' of the information for care and planning, information sharing, research and quality assurance. PMID- 22313562 TI - Impact of pain location, organ system and treating speciality on timely delivery of analgesia in emergency departments. AB - OBJECTIVE: This retrospective, observational cohort study investigated whether the clinical features of a patient's pain, including anatomical location, organ system and likely treating speciality, impact on the delivery of analgesia within 30 min in EDs. METHODS: Data were obtained from 24 centres across Australia between April 2008 and March 2009. Principal outcome was delivery of analgesia within 30 min or less. Factors that might explain any differences were analysed, including anatomical location of the pain, likely treating speciality, organ system affected, age, sex, day and time of presentation, hospital location, documented pain score and triage category. Analysis was by the chi(2)-test for independence of proportions and multiple logistic regression. A P-value <0.05 was considered statistically significant. RESULTS: There were 4598 patients, of whom 2578 were male. The median age was 36 years (range 0-103). Both limb origin of pain (chi(2) = 46.1, P < 0.001) and documentation of a pain score (chi(2) = 48.6, P < 0.001) were strongly associated with delivery of analgesia within 30 min. Attending a rural ED was a significant risk factor for delayed analgesia (chi(2) = 12.5, P < 0.001). Burns patients (40.2%, 47 of 117, P < 0.001) and orthopaedic patients (26.1%, 259 of 992, P < 0.001) were much more likely to received analgesia within 30 min than the mean (19.5%, 896 of 4598). CONCLUSIONS: Patients presenting with burns, orthopaedic conditions or with a limb location of pain are more likely to receive analgesia within 30 min in Australian EDs. Clinicians should be aware of possible trends in the delivery of timely analgesia to patients with pain. PMID- 22313563 TI - Demand for public hospital emergency department services in Australia: 2000-2001 to 2009-2010. AB - OBJECTIVE: Hospital EDs are a significant and high-profile component of Australia's health-care system, which in recent years have experienced considerable crowding. This crowding is caused by the combination of increasing demand, throughput and output factors. The aim of the present article is to clarify trends in the use of public ED services across Australia with a view to providing an evidence basis for future policy analysis and discussion. METHODS: The data for the present article have been extracted, compiled and analysed from publicly available sources for a 10 year period between 2000-2001 and 2009-2010. RESULTS: Demand for public ED care increased by 37% over the decade, an average annual increase of 1.8% in the utilization rate per 1000 persons. There were significant differences in utilization rates and in trends in growth among states and territories that do not easily relate to general population trends alone. CONCLUSIONS: This growth in demand exceeds general population growth, and the variability between states both in utilization rates and overall trends defies immediate explanation. The growth in demand for ED services is a partial contributor to the crowding being experienced in EDs across Australia. There is a need for more detailed study, including qualitative analysis of patient motivations in order to identify the factors driving this growth in demand. PMID- 22313564 TI - How fast does oral dexamethasone work in mild to moderately severe croup? A randomized double-blinded clinical trial. AB - OBJECTIVE: For children with croup controversy remains over dosage and time to onset of action of oral steroids. The Cochrane Collaboration and other reviews have suggested 0.6 mg/kg dexamethasone be used (despite some evidence that 0.15 mg/kg is effective) with no expectation of benefit before 4-6 h. This randomized double-blinded clinical trial examines whether 0.15 mg/kg dexamethasone works by 30 min. METHODS: Children with croup aged above 6 months presenting to a tertiary paediatric ED with a Westley croup score of mild to moderate range (scores 1-6 out of 17) were randomized to receive either 0.15 mg/kg dexamethasone or oral placebo solution. Vital signs and croup score were recorded at study entry and every 10 min up to 1 h after administration of the study drug. The main outcome measure was croup score at 30 min. RESULTS: Each group contained 35 children. Baseline characteristics were similar, except for respiratory rate, which was higher in the placebo group. There was a growing trend to a lower croup score in the dexamethasone group, evident from 10 min and statistically significant from 30 min. CONCLUSION: For children with croup an oral dose of 0.15 mg/kg dexamethasone offers benefit by 30 min, much earlier than the 4 h suggested by the Cochrane Collaboration. This result might encourage doctors to treat more children with all severities of croup being less worried about potential side effects and delayed benefit. PMID- 22313565 TI - Survey of paediatric intravenous fluid prescription: are we safe in what we know and what we do? AB - OBJECTIVE: The administration of i.v. fluids to children is common in hospital. There are risks associated with fluid therapy, especially iatrogenic hyponatraemia. The objective of this study was to assess the workplace practices and knowledge of tertiary hospital doctors regarding paediatric i.v. fluid prescription. METHODS: This is a prospective, questionnaire-based observational study conducted at a 570-bed teaching hospital in June 2009. A convenience sample of doctors (n= 150), representing all levels of experience and all specialties that regularly prescribe paediatric i.v. fluids, were invited to participate. The main outcome measures consisted of demographical data and the ability to correctly prescribe paediatric fluids measured as 'fluid calculation', 'fluid choice' and 'total' percentage scores based on a percentage score of correctly answered questions using eight clinical scenarios. RESULTS: One hundred and six (71%) doctors returned a completed questionnaire. The great majority of respondents had a method for calculating a fluid bolus and maintenance rates (91% and 97%, respectively). Scenarios involving infants, especially where an increased risk of antidiuretic hormone secretion was possible, were answered poorly. Senior doctors performed better than junior doctors. ED and paediatric doctors performed better than those in other specialities. CONCLUSIONS: Most doctors in this Australian tertiary hospital have a correct method for prescribing bolus and maintenance fluid rates. However, the potential for adverse events from i.v. fluid prescription remains. Further education in this area for junior doctors, introduction of standardized guidelines for fluid use and restriction of available fluid choice may reduce the risk of iatrogenic hyponatraemia in children. PMID- 22313566 TI - Hydrofluoric acid poisoning: data from the Victorian Poisons Information Centre. AB - OBJECTIVE: To determine the epidemiology of hydrofluoric acid (HF) exposures, over an extended time period, in Victoria, Australia. METHODS: Retrospective case review of all HF exposures from calls to the Victorian Poisons Information Centre (VPIC) from June 2005 to February 2011. RESULTS: The VPIC received calls regarding 75 separate HF exposures (approximately 12 per year). The majority 68 (91%) of calls related to male patients. Sixty-nine (92%) calls related to adults, six (8%) to children (<12 years) and none to the elderly (>65 years age). Fifty-three per cent of exposures occurred at the workplace. Dermal exposures comprised 54 (72%). Forty-six (85%) of these resulted from hand contact, six (11%) arm and two (4%) legs. The second most common exposure was ocular 11 (15%). More than half of exposures involved HF concentrations of 10% or less. Of the dermal exposures treated in EDs, 16% required calcium treatment in a form other than gel. Overall poisoning severity was mild (79% of cases Poisoning Severity Score of 0 or 1). Health professionals were the most frequent callers (53% of all cases). CONCLUSIONS: Calls to the VPIC regarding HF are relatively rare, but almost all calls regarding HF taken by the VPIC required hospital evaluation. The majority of exposures were accidental occupational dermal exposures in male adults and most of these were minor, requiring topical calcium gel only. Small exposures with higher concentrated HF can be fatal; however, there were no cases of severe toxicity in the present study. PMID- 22313567 TI - Palliative care in the emergency department: an oxymoron or just good medicine? AB - In 2006, the American Board of Emergency Medicine co-sponsored hospice and palliative medicine as a recognized medical subspecialty. There is recognition of the need for these skills to be available in EDs in the USA. This article discusses the rationale for integrating a palliative approach in the ED. We need to engage our palliative care colleagues to increase clinical support to meet the needs of these vulnerable patients and to foster collaborative educational opportunities. PMID- 22313568 TI - Exposure of Iranian emergency medical technicians to workplace violence: a cross sectional analysis. AB - OBJECTIVES: Emergency medical technicians (EMTs) in Iran experience concerning levels of workplace violence, although until now there has been no investigation of this phenomenon. The objectives of the present study were to describe the exposure of Iranian EMTs to workplace violence and to identify the importance of related factors from their viewpoint. METHODS: In this descriptive, exploratory study, 160 EMTs agreed to participate in a survey that collected data regarding their exposure to the following forms of workplace violence: verbal abuse, physical assault, cultural harassment, sexual harassment and sexual assault. RESULTS: A total of 138 questionnaires were returned, representing a response rate of 86%. The majority of participants 75% (n = 103) experienced at least one form of workplace violence in the 12 months before completing the questionnaire. The most frequently reported form of workplace violence was verbal abuse (71%), followed by physical assault (38%) and cultural harassment (9%). Violence resulting in serious injuries was reported by only 4% of participants, with no more than 8% of participants experiencing workplace violence that included the use of weapons. The most reported response to workplace violence was to 'invite the offender to calm down'. Participants took this approach because they believed that 'follow up of workplace violence is ineffectual' (34%), considered the workplace violence as a common in their job (30%), and did not know whom to report workplace violence to (13%). CONCLUSION: Iranian EMTs experience a considerable amount of workplace violence. The present study highlights the recommendation for formal training programmes and clearer protocols about how to manage workplace violence, especially verbal abuse in the Iranian prehospital setting. PMID- 22313569 TI - Acute ST-elevation myocardial infarction in a 24-year-old woman with atheromatous coronary artery disease. AB - We report the case of a 24-year-old Torres Strait Islander woman who presented to a rural hospital ED with chest pain suspicious for myocardial ischaemia and was found to have an anterior ST-elevation myocardial infarction. She was thrombolysed and transferred to a tertiary centre where subsequent angiography revealed atheromatous disease of the left anterior descending coronary artery. We believe this to be one of the youngest reported cases of myocardial infarction due to atheromatous coronary artery disease, and demonstrates important learning points regarding the demographics and risk factors of indigenous patients with chest pain. PMID- 22313570 TI - Selective versus mandatory whole-body computed tomography scanning in the multiply injured patient. PMID- 22313571 TI - Myth of tension spontaneous pneumothorax. PMID- 22313572 TI - How do clinicians obtain urine samples in young children? PMID- 22313574 TI - Leptin deficiency-induced obesity affects the density of mast cells in abdominal fat depots and lymph nodes in mice. AB - BACKGROUND: Mast cells are implicated in the pathogenesis of obesity and insulin resistance. Here, we explored the effects of leptin deficiency-induced obesity on the density of mast cells in metabolic (abdominal fat depots, skeletal muscle, and liver) and lymphatic (abdominal lymph nodes, spleen, and thymus) organs. Fourteen-week-old male leptin-deficient ob/ob mice and their controls fed a standard chow were studied. Tissue sections were stained with toluidine blue to determine the density of mast cells. CD117/c-kit protein expression analysis was also carried out. Furthermore, mast cells containing immunoreactive tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine involved in obesity linked insulin resistance, were identified by immunostaining. RESULTS: ob/ob mice demonstrated adiposity and insulin resistance. In abdominal fat depots, mast cells were distributed differentially. While most prevalent in subcutaneous fat in controls, mast cells were most abundant in epididymal fat in ob/ob mice. Leptin deficiency-induced obesity was accompanied by a 20-fold increase in the density of mast cells in epididymal fat, but a 13-fold decrease in subcutaneous fat. This finding was confirmed by CD117/c-kit protein expression analysis. Furthermore, we found that a subset of mast cells in epididymal and subcutaneous fat were immunoreactive for TNF-alpha. The proportion of mast cells immunoreactive for TNF-alpha was higher in epididymal than in subcutaneous fat in both ob/ob and control mice. Mast cells were also distributed differentially in retroperitoneal, mesenteric, and inguinal lymph nodes. In both ob/ob mice and lean controls, mast cells were more prevalent in retroperitoneal than in mesenteric and inguinal lymph nodes. Leptin deficiency-induced obesity was accompanied by increased mast cell density in all lymph node stations examined. No significant difference in the density of mast cells in skeletal muscle, liver, spleen, and thymus was noted between ob/ob and control mice. CONCLUSIONS: This study demonstrates that leptin deficiency-induced obesity is accompanied by alterations in the density of mast cells in abdominal fat depots. The divergent distribution of mast cells in subcutaneous versus visceral fat might partially account for their differential biological behavior. Mast cells might also play a role in adaptive immune response occurring in regional lymph nodes in obesity. PMID- 22313575 TI - The development of Psychodiella sergenti (Apicomplexa: Eugregarinorida) in Phlebotomus sergenti (Diptera: Psychodidae). AB - Psychodiella sergenti is a recently described specific pathogen of the sand fly Phlebotomus sergenti, the main vector of Leishmania tropica. The aim of this study was to examine the life cycle of Ps. sergenti in various developmental stages of the sand fly host. The microscopical methods used include scanning electron microscopy, transmission electron microscopy and light microscopy of native preparations and histological sections stained with periodic acid-Schiff reaction. Psychodiella sergenti oocysts were observed on the chorion of sand fly eggs. In 1st instar larvae, sporozoites were located in the ectoperitrophic space of the intestine. No intracellular stages were found. In 4th instar larvae, Ps. sergenti was mostly located in the ectoperitrophic space of the intestine of the larvae before defecation and in the intestinal lumen of the larvae after defecation. In adults, the parasite was recorded in the body cavity, where the sexual development was triggered by a bloodmeal intake. Psychodiella sergenti has several unique features. It develops sexually exclusively in sand fly females that took a bloodmeal, and its sporozoites bear a distinctive conoid (about 700 nm long), which is more than 4 times longer than conoids of the mosquito gregarines. PMID- 22313576 TI - Spirulina is an effective dietary source of zeaxanthin to humans. AB - Zeaxanthin is a predominant xanthophyll in human eyes and may reduce the risk of cataracts and age-related macular degeneration. Spirulina is an algal food that contains a high concentration of zeaxanthin. In order to determine the zeaxanthin bioavailability of spirulina for dietary supplementation in humans, spirulina was grown in nutrient solution with 2H2O for carotenoid labelling. Single servings of 2H-labelled spirulina (4.0-5.0 g) containing 2.6-3.7 mg zeaxanthin were consumed by fourteen healthy male volunteers (four Americans and ten Chinese) with 12 g dietary fat. Blood samples were collected over a 45 d period. The serum concentrations of total zeaxanthin were measured using HPLC, and the enrichment of labelled zeaxanthin was determined using LC-atmospheric pressure chemical ionisation-MS (LC-APCI-MS). The results showed that intrinsically labelled spirulina zeaxanthin in the circulation was detected at levels as low as 10 % of the total zeaxanthin for up to 45 d after intake of the algae. A single dose of spirulina can increase mean serum zeaxanthin concentration in humans from 0.06 to 0.15 MUmol/l, as shown in our study involving American and Chinese volunteers. The average 15 d area under the serum zeaxanthin response curve to the single dose of spirulina was 293 nmol * d/MUmol (range 254-335) in American subjects, and 197 nmol * d/MUmol (range 154-285) in Chinese subjects. It is concluded that the relative bioavailability of spirulina zeaxanthin can be studied with high sensitivity and specificity using 2H labelling and LC-APCI-MS methodology. Spirulina can serve as a rich source of dietary zeaxanthin in humans. PMID- 22313577 TI - Defunct brain stem cardiovascular regulation underlies cardiovascular collapse associated with methamphetamine intoxication. AB - BACKGROUND: Intoxication from the psychostimulant methamphetamine (METH) because of cardiovascular collapse is a common cause of death within the abuse population. For obvious reasons, the heart has been taken as the primary target for this METH-induced toxicity. The demonstration that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse induced by the pesticide mevinphos implicates another potential underlying mechanism. The present study evaluated the hypothesis that METH effects acute cardiovascular depression by dampening the functional integrity of baroreflex via an action on brain stem nuclei that are associated with this homeostatic mechanism. METHODS: The distribution of METH in brain and heart on intravenous administration in male Sprague-Dawley rats, and the resultant changes in arterial pressure (AP), heart rate (HR) and indices for baroreflex-mediated sympathetic vasomotor tone and cardiac responses were evaluated, alongside survival rate and time. RESULTS: Intravenous administration of METH (12 or 24 mg/kg) resulted in a time-dependent and dose-dependent distribution of the psychostimulant in brain and heart. The distribution of METH to neural substrates associated with brain stem cardiovascular regulation was significantly larger than brain targets for its neurological and psychological effects; the concentration of METH in cardiac tissues was the lowest among all tissues studied. In animals that succumbed to METH, the baroreflex-mediated sympathetic vasomotor tone and cardiac response were defunct, concomitant with cessation of AP and HR. On the other hand, although depressed, those two indices in animals that survived were maintained, alongside sustainable AP and HR. Linear regression analysis further revealed that the degree of dampening of brain stem cardiovascular regulation was positively and significantly correlated with the concentration of METH in key neural substrate involved in this homeostatic mechanism. CONCLUSIONS: We conclude that on intravenous administration, METH exhibits a preferential distribution to brain stem nuclei that are associated with cardiovascular regulation. We further found that the concentration of METH in those brain stem sites dictates the extent that baroreflex-mediated sympathetic vasomotor tone and cardiac responses are compromised, which in turn determines survival or fatality because of cardiovascular collapse. PMID- 22313579 TI - Effects of confinement on thermal stability and folding kinetics in a simple Ising-like model. AB - In a cellular environment, confinement and macromolecular crowding play an important role in thermal stability and folding kinetics of a protein. We have resorted to a generalized version of the Wako-Saito-Munoz-Eaton model for protein folding to study the behavior of six different protein structures confined between two walls. Changing the distance 2R between the walls, we found, in accordance with previous studies, two confinement regimes: starting from large R and decreasing R, confinement first enhances the stability of the folded state as long as this is compact and until a given value of R; then a further decrease of R leads to a decrease of folding temperature and folding rate. We found that in the low confinement regime, both unfolding temperatures and logarithm of folding rates scale as R(-gamma) where gamma values lie in between 1.42 and 2.35. PMID- 22313578 TI - Drug development in pediatric psychiatry: current status, future trends. PMID- 22313580 TI - Management of neuropathic pain with methylprednisolone at the site of nerve injury. AB - OBJECTIVE: Peripheral nerve blocks with methylprednisolone may provide effective pain therapy by decreasing ectopic neuronal discharge and the release of local inflammatory mediators at the site of nerve injury. In this study, we aimed to compare the efficacy of lidocaine alone with a combination of depo methylprednisolone plus lidocaine in the management of neuropathic pain due to peripheral nerve damage. DESIGN: Randomized, double-blind comparator trial. SETTING: Group control (N = 44) received 0.5% lidocaine and group methylprednisolone (N = 44) received 80 mg depo-methylprednisolone + 0.5% lidocaine proximal to the site of nerve injury with a total amount of 10-20 mL solution according to the type of peripheral nerve block with nerve stimulator. OUTCOME MEASURES: Demographic data, preblock numerical rating scales (NRSs), the Leeds assessment of neuropathic symptoms and signs (LANSS(0) ) score, accompanying symptoms, and analgesic requirements were recorded. Postblock NRS scores were noted following peripheral nerve block and after 3 months. LANSS(1) , accompanying symptoms, and analgesic requirements were also reevaluated 3 months after the injection. RESULTS: Demographic data, preblock NRS (8 +/- 1.5 and 8.1 +/- 1.2, respectively), postblock NRS (2.1 +/- 1.2 and 2.4 +/- 1.4, respectively), LANSS(0) (18.4 +/- 2.2 and 18.2 +/- 2.1, respectively), and accompanying symptoms were comparable between groups. Scores for the methylprednisolone group were significantly improved at 3-month postblock for NRS (2 +/- 1.4 vs 5.2 +/- 1.7) and LANSS(1) scores (4.14 +/- 2.7 vs 14.1 +/- 2.8), accompanying symptoms, and analgesic requirements (P < 0.0001). CONCLUSIONS: Our results suggest that peripheral nerve block with 80 mg depo-methylprednisolone plus 0.5% lidocaine provides effective management in the treatment of neuropathic pain due to peripheral nerve damage. PMID- 22313581 TI - Physical performance and daily walking duration: associations in 1271 women and men aged 65-90 years. AB - BACKGROUND AND AIMS: Several tests of physical performance like gait speed or standing balance are part of the geriatric assessment. Measures of physical activity like daily walking duration are more difficult to assess but may be of higher relevance for daily requirements. It is therefore of interest to what extent physical performance measures are associated with physical activity. METHODS: In a cohort study, baseline screening was performed in 1271 community living people aged 65-90 years from Ulm, Germany. Average daily walking duration was assessed in all participants by accelerometers over a one-week period. Habitual gait speed, 5-Chair-Rise test, standing balance and handgrip strength served as measures of physical performance. The association between measures of physical performance and physical activity was calculated by linear regression analysis. RESULTS: The mean daily walking duration was 104.8 minutes in men and 103.0 minutes in women. A positive relationship between gait speed and walking duration was observed in men and women with low gait speed (<=0.8 m/s) but not in participants above this threshold. Standing balance and hand grip strength were positively and 5-Chair-Rise test inversely related with average daily walking duration. A relationship between hand grip strength and walking duration was only observed in women aged 75 years and more. CONCLUSIONS: Physical performance measures and objectively measured walking duration are related with each other but only a small percentage of the variance of daily walking duration was explained by physical performance measures. Therefore, factors other than physical performance seem to influence daily walking duration to a great extent. PMID- 22313582 TI - Validation of a novel robotic-assisted partial nephrectomy surgical training model. AB - What's known on the subject? and What does the study add? One area of particular growth for robotic surgery has been partial nephrectomy. Despite a perceived notion that robotic-assisted partial nephrectomy is more easily adaptable compared to laparoscopic partial nephrectomy, there is nonetheless an associated learning curve. Validated training models with a corresponding assessment method for robotic-assisted partial nephrectomy were previously unavailable. We have designed and validated a RAPN surgical model appropriate for resident and fellow training. OBJECTIVE: To evaluate the face, content and construct validities of a novel ex vivo surgical training model for robotic-assisted partial nephrectomy (RAPN). METHODS: We prospectively identified participants as novice (not completed any robotic console cases), intermediate (at least one robotic console case but <100 cases), and expert (>=100 robotic console cases). Each participant performed a partial nephrectomy using the da Vinci Si Surgical System on an ex vivo porcine kidney with an embedded Styrofoam ball that mimics a renal tumour. Subjects completed a post-study questionnaire assessing training model realism and utility. Participants were anonymously judged by three expert reviewers using a validated laparoscopic assessment tool. Performance between groups was compared using the tukey-kramer test. RESULTS: The 46 participants recruited for this study included 24 novices, nine intermediates, and 13 experts. Overall, expert surgeons rated the training model as 'very realistic' (median visual analogue score 7/10) (face validity). Experts also rated the model as an 'extremely useful' training tool for residents (median 9/10) and fellows (9/10) (content validity), although less so for experienced robotic surgeons (5/10). Experts outscored novices on overall performance (P = 0.0002) as well as individual metrics, including 'depth perception,''bimanual dexterity,''efficiency,''tissue handling,''autonomy,''precision,' and 'instrument and camera awareness' (P < 0.05) (construct validity). Experts similarly outperformed intermediates in most metrics (P < 0.05). CONCLUSION: Our novel ex vivo RAPN surgical model has demonstrated face, content and construct validity. Future development of this model should include simulation of haemostasis management and renal reconstruction. PMID- 22313583 TI - Promoting healthy eating in pregnancy: what kind of support services do women say they want? AB - AIM: To identify characteristics of the services and support women want to enable them to eat healthily during pregnancy to make a potential future service acceptable to this population. BACKGROUND: An unhealthy diet during pregnancy may have a significant influence on pregnancy outcome, either directly through nutrient deficiencies or indirectly through maternal weight gain. Many pregnant women in the United Kingdom gain too much weight in pregnancy, and this weight gain may lead to an increased risk of preeclampsia, gestational diabetes and having an obese child. Thus, there is a need for interventions aimed at improving healthy eating in pregnancy. It is crucial in developing successful interventions to understand how participation can be maximised by optimising intervention acceptability. METHODS: Four focus groups were conducted; two with prenatal women (n = 9) and two with postnatal women (n = 14). Discussion focused on identifying relevant characteristics of a service targeting prenatal and postnatal women's eating to ensure that a future service was acceptable to the women. FINDINGS: The participants' responses were clustered into three broad themes: (1) early information leading to routine formation of healthier eating habits, (2) the delivery of practical sessions to increase information and (3) health professionals providing support and signposting to services. The participants reported wanting a practical service held in a convenient location, preferably led by women who have been pregnant themselves. The participants also reported wanting to be offered this service in pregnancy to help them get into a routine before they gave birth. Several suggestions for how this service should be marketed were mentioned, including through midwives and the internet. This research provides practical information for how to design support for prenatal women to increase their knowledge and practical skills regarding eating healthily during their pregnancy. PMID- 22313585 TI - Nuclear matrix protein-22: a prospective evaluation in a population at risk for bladder cancer. Results from the UroScreen study. AB - What's known on the subject? and What does the study add? The prognosis of bladder cancer significantly depends on tumour stage and time of diagnosis so early diagnosis is desirable to decrease mortality and treatment costs. The NMP22 test is approved for clinical application by the Food and Drug Administration (FDA) of the US. Previous studies have reported values of 47-100% for sensitivity and 58-91% for specificity with this test, but there is no new data on the predictive value of NMP22 for screening bladder cancer (BC). The most important risk factor for BC is the tobacco consumption but occupational exposure to carcinogenic substances, especially aromatic amines, is regarded as another risk factor. The UroScreen study is a prospective longitudinal study for the early detection of BC. To our knowledge, it is the largest prospective validation study conducted over the longest period of time. The study results led us to conclude that, based on the currently available data, NMP22 should not be regarded as an alternative to endoscopy, and we could not make a general recommendation for screening or follow-up. The UroScreen results indicate that urine-based molecular markers could be a suitable addition to urine cytology and the detection of microhaematuria. OBJECTIVE: To evaluate the value of nuclear matrix protein-22 (NMP22) in bladder cancer (BC) screening, and its effect on variables in a prospective study in a high-risk population. PATIENTS AND METHODS: A total of 1772 chemical workers (mean age 62 years) exposed to carcinogenic aromatic amines were enrolled in the study. In all, 7091 screening check-ups in 1609 subjects were performed. Urine samples were collected for a quantitative NMP22 immunoassay, urine analysis and creatinine concentration assessment. Cystoscopy and subsequent transurethral resection were performed where there were suspicious findings. RESULTS: Histopathological analysis found three papillary urothelial neoplasms of low malignant potential, five recurrent BCs and 13 primary BCs. Three tumours were at a muscle-invasive stage (pT2, pT3a or pT3b). We found higher NMP22 concentrations (>10 U/mL) in 224 patients, which correctly predicted BC in six cases (sensitivity 97.29%, specificity 28.57%; negative predictive value 99.04%, positive predictive value 12.24%). Gross haematuria affected NMP22 results (odd ratio [OR] 3.49, 95% confidence interval [CI] 1.81-6.73). Infection also affected NMP22 results (OR 4.13, 95% CI 2.31-7.35). NMP22 was more frequently positive in urine with creatinine concentration >2.5 g/L (OR 1.61, 95% CI 0.91-2.86). CONCLUSIONS: NMP22 outcomes are affected by haematuria, infection and concentrated urine. NMP22 alone cannot be recommended for primary screening in a high-risk population nor as an alternative to cystoscopy during follow-up. A NMP22 test might be a useful adjunct to urine cytology. PMID- 22313584 TI - Effect of conjugated linoleic acid on inhibition of prolyl hydroxylase 1 in hearts of mice. AB - BACKGROUND: Results from different trails have provided evidence of protective effects of cis-9,trans-11-conjugated linoleic acid (CLA) on cardiovascular diseases. But the inhibition of prolyl hydroxylase 1 (PHD1) associated with induction of hypoxia inducible factors (HIFs) by CLA in these protective effects has never been reported before. The objective of this study was to evaluate if the two predominant cis-9,trans-11 (c9, t11), trans-10,cis-12 (t10, c12) CLA isomers and mixture of these two isomers can inhibit PHD1 with induction of HIFs in myocardium in mice and subsequent effects on myocardium metabolism. RESULTS: CLA mixture and c9, t11 CLA inhibited PHD1 protein expression and increased the levels of protein and mRNA in HIF-2alpha in myocardium in mice. Meanwhile, CLA mixture and c9, t11 CLA also elevated the expression of HIF related transcriptional factors like PDK4 and PPARalpha. The reprogramming of basal metabolism in myocardium in mice was shown on increasing of GLUT4 gene expression by c9, t11 CLA supplemented group. UCP2 was increased by CLA mixture and c9, t11 CLA for attenuating production of ROS. CONCLUSION: CLA mixture and c9, t11 CLA could inhibit PHD1 and induce HIF-2alpha in myocardium in mice, which is associated with upregulation of PDK4 by activation of PPARalpha. This process also implies a reprogramming of basal metabolism and oxidative damage protection in myocardium in mice. All the effects shown in hearts of mice are due to c9, t11 CLA but not t10, c12 CLA. PMID- 22313586 TI - Correlation of the BRAF V600E mutation in hairy cell leukaemia with morphology, cytochemistry and immunophenotype. AB - Hairy cell leukaemia (HCL) has distinct clinical, morphological and immunophenotypic features with no recurrent cytogenetic or molecular abnormalities reported until the recent description of the BRAF V600E mutation in patients with classical HCL. The incidence of this mutation was sought in 27 patients with either classical HCL or HCL variant by an allele-specific PCR approach and findings related to morphology, cytochemistry and immunophenotype. A high degree of correlation was noted between the presence of BRAF V600E and established diagnostic criteria in 26/27 patients with HCL/HCL variant. Detection of the BRAF V600E mutation is therefore a useful adjunct in the differential diagnosis of HCL and HCL variant and highlights the value of a multifaceted approach to the diagnosis of this malignancy. PMID- 22313587 TI - Effect of different long-chain fatty acids on cholecystokinin release in vitro and energy intake in free-living healthy males. AB - Long-chain fatty acids have been shown to suppress appetite and reduce energy intake (EI) by stimulating the release of gastrointestinal hormones such as cholecystokinin (CCK). The effect of NEFA acyl chain length on these parameters is not comprehensively understood. An in vitro screen tested the capacity of individual NEFA (C12 to C22) to trigger CCK release. There was a gradient in CCK release with increasing chain length. DHA (C22) stimulated significantly (P < 0.01) more CCK release than all other NEFA tested. Subsequently, we conducted a randomised, controlled, crossover intervention study using healthy males (n 18). The effects of no treatment (NT) and oral doses of emulsified DHA-rich (DHA) and oleic acid (OA)-rich oils were compared using 24 h EI as the primary endpoint. Participants reported significantly (P = 0.039) lower total daily EI (29 % reduction) with DHA compared to NT. There were no differences between DHA compared to OA and OA compared to NT. There was no between-treatment difference in the time to, or EI of, the first post-intervention eating occasion. It is concluded that NEFA stimulate CCK release in a chain length-dependent manner up to C22. These effects may be extended to the in vivo setting, as a DHA-based emulsion significantly reduced short-term EI. PMID- 22313588 TI - Schistosomiasis in infants and pre-school-aged children in sub-Saharan Africa: implication for control. AB - Until recently, the epidemiology and control of schistosomiasis in sub-Saharan Africa have focused primarily on infections in school-aged children and to a lesser extent on adults. Now there is growing evidence and reports of infection in infants and pre-school-aged children (<= 6 years old) in Ghana, Kenya, Mali, Niger, Nigeria and Uganda, with reported prevalence from 14% to 86%. In this review, we provide available information on the epidemiology, transmission and control of schistosomiasis in this age group, generally not considered or included in national schistosomiasis control programmes that are being implemented in several sub-Saharan African countries. Contrary to previous assumptions, we show that schistosomiasis infection starts from early childhood in many endemic communities and factors associated with exposure of infants and pre-school-aged children to infection are yet to be determined. The development of morbidity early in childhood may contribute to long-term clinical impact and severity of schistosomiasis before they receive treatment. Consistently, these issues are overlooked in most schistosomiasis control programmes. It is, therefore, necessary to review current policy of schistosomiasis control programmes in sub-Saharan Africa to consider the treatment of infant and pre school-aged children and the health education to mothers. PMID- 22313589 TI - Rapid evolution of parasite life history traits on an expanding range-edge. AB - Parasites of invading species undergoing range advance may be exposed to powerful new selective forces. Low host density in range-edge populations hampers parasite transmission, requiring the parasite to survive longer periods in the external environment before encountering a potential host. These conditions should favour evolutionary shifts in offspring size to maximise parasite transmission. We conducted a common-garden experiment to compare life history traits among seven populations of the nematode lungworm (Rhabdias pseudosphaerocephala) spanning from the parasite population core to the expanding range-edge in invasive cane toads (Rhinella marina) in tropical Australia. Compared to conspecifics from the population core, nematodes from the range-edge exhibited larger eggs, larger free living adults and larger infective larvae, and reduced age at maturity in parasitic adults. These results support a priori predictions regarding adaptive changes in offspring size as a function of invasion history, and suggest that parasite life history traits can evolve rapidly in response to the selective forces exerted by a biological invasion. PMID- 22313590 TI - Functional analysis of hepatitis B virus pre-s deletion variants associated with hepatocellular carcinoma. AB - BACKGROUND: Naturally occurring pre-S deletion mutants have been identified in hepatitis B carriers and shown to be associated with the development of hepatocellular carcinoma. The phenotypes of these pre-S deletion genomes remain unclear, and they were investigated in this study. METHODS: The pre-S deletion genomes: (1) pre-S1 deletion, (2) deletion spanning pre-S1 and pre-S2, (3) pre-S2 N-terminal deletion, and (4) pre-S2 internal deletion were constructed and analyzed by transfection into Huh-7 cells. RESULTS: Functional analyses reveal that these mutants were divided into two groups: S promoter deletion and non-S promoter deletion variants. Compared with the wild-type genome, S promoter deletion variants led to an inverse ratio of pre-S1 mRNA and pre-S2/S mRNA, and intracellular accumulation of surface proteins. An interesting finding is that a small amount of L proteins was detected in the medium from S promoter deletion variant-transfected cells. Non-S promoter deletion variants conversely displayed a wild-type like mRNA and protein pattern. The secretion of surface proteins from non-S promoter deletion variants was inhibited less than from S promoter deletion variant. Immunofluorescence analysis showed mutant surface proteins colocalized with ER and exhibited an atypical distribution: granular staining pattern in the S-promoter deletion variants and perinuclear staining pattern in the non-S promoter deletion variants. CONCLUSION: This study shows that these pre-S deletion genomes exhibit two different phenotypes in mRNA transcription, surface protein expression and secretion. This diversity seems to result from the deletion of S promoter rather than result from the deletion of pre-S1 or pre-S2. PMID- 22313591 TI - A descriptive feasibility study to evaluate scheduled oral analgesic dosing at home for the management of postoperative pain in preschool children following tonsillectomy. AB - OBJECTIVES: The purpose of this study, in a sample of preschool children (ages 3 5 years; N = 47), was to evaluate the feasibility of scheduled analgesic dosing following outpatient tonsillectomy in order to optimize pain management. METHODS: Parents were instructed to give their child acetaminophen with hydrocodone (167 mg/5 mL) every 4 hours around the clock for the first 3 days following surgery. Parents recorded ratings of their child's pain with/without swallowing using the Faces, Legs, Activity, Cry, and Consolability (FLACC) behavioral pain scale, pain relief ratings, and severity of analgesic side effects in a home diary. Audiotaped interviews were conducted with parents to document descriptions of their experiences in managing their child's pain at home. RESULTS: Mean FLACC scores with/without swallowing were less than two at each measurement time and pain relief scores increased over time. Total analgesic dose decreased, and the number of missed doses increased over the first 3 days after surgery. Moderate-to severe daytime sedation, nausea, vomiting, and constipation were reported by parents. DISCUSSION: Study results suggest that acetaminophen with hydrocodone is effective in relieving preschool children's pain following tonsillectomy and that parental adherence to a scheduled analgesic regimen decreases over time. Time contingent dosing was associated with moderate to severe side effects and should be addressed in discharge teaching with parents. Findings provide insight into parents' perspective of pain management at home following tonsillectomy and methods for relieving their child's pain. PMID- 22313592 TI - Involvement of the atrial natriuretic peptide in cardiovascular pathophysiology and its relationship with exercise. AB - In this minireview we describe the involvement of the atrial natriuretic peptide (ANP) in cardiovascular pathophysiology and exercise. The ANP has a broad homeostatic role and exerts complex effects on the cardio-circulatory hemodynamics, it is produced by the left atrium and has a key role in regulating sodium and water balance in mammals and humans. The dominant stimulus for its release is atrial wall tension, commonly caused by exercise. The ANP is involved in the process of lipolysis through a cGMP signaling pathway and, as a consequence, reducing blood pressure by decreasing the sensitivity of vascular smooth muscle to the action of vasoconstrictors and regulate fluid balance. The increase of this hormone is associated with better survival in patients with chronic heart failure (CHF). This minireview provides new evidence based on recent studies related to the beneficial effects of exercise in patients with cardiovascular disease, focusing on the ANP. PMID- 22313593 TI - Laparoscopic versus open colectomy for colon cancer in an older population: a cohort study. AB - BACKGROUND: Laparoscopic colectomy for colon cancer has been compared with open colectomy in randomized controlled trials, but these studies may not be generalizable because of strict enrollment and exclusion criteria which may explicitly or inadvertently exclude older individuals due to associated comorbidities. Previous studies of older patients undergoing laparoscopic colectomy have generally focused on short-term outcomes. The goals of this cohort study were to identify predictors of laparoscopic colectomy in an older population in the United States and to compare short-term and long-term outcomes. METHODS: Patients aged 65 years or older with incident colorectal cancer diagnosed 1996-2002 who underwent colectomy within 6 months of cancer diagnosis were identified from the linked Surveillance, Epidemiology, and End Results Medicare database. Laparoscopic and open colectomy patients were compared with respect to length of stay, blood transfusion requirements, intensive care unit monitoring, complications, 30-day mortality, and long-term survival. We adjusted for potential selection bias in surgical approach with propensity score matching. RESULTS: Laparoscopic colectomy cases were associated with left-sided tumors; areas with higher population density, income, and education level; areas in the western United States; and National Cancer Institute-designated cancer centers. Laparoscopic colectomy cases had shorter length of stay and less intensive care unit monitoring. Although laparoscopic colectomy patients (n = 424) had fewer complications (21.5% versus 26.3%), lower 30-day mortality (3.3% versus 5.8%), and longer median survival (6.6 versus 4.8 years) compared with open colectomy patients (n = 27,012), after propensity score matching these differences disappeared. CONCLUSIONS: In this older population, laparoscopic colectomy practice patterns were associated with factors which likely correlate with tertiary referral centers. Although short-term and long-term survival are comparable, laparoscopic colectomy offers shorter hospitalizations and less intensive care. PMID- 22313594 TI - Prognostic value of the lymph node ratio in stage III colorectal cancer. AB - The nodal stage of colorectal cancer is based on the number of positive nodes. It is inevitably affected by the number of removed lymph nodes, but lymph node ratio can be unaffected. We investigated the value of lymph node ratio in stage III colorectal cancer in this study. The clinicopathologic factors and follow-up data of 145 cases of stage III colorectal cancer between January 1998 and December 2008 were analyzed retrospectively. The Pearson and Spearman correlation analyses were used to determine the correlation coefficient, the Kaplan-Meier method was used to analyze survival, and the Cox proportional hazard regression model was used for multivariate analysis in forward stepwise regression. We found that lymph node ratio was not correlated with the number of removed lymph nodes (r = 0.154, P = 0.065), but it was positively correlated with the number of positive lymph nodes (r = 0.739, P < 0.001) and N stage (r = 0.695, P < 0.001). Kaplan Meier survival analysis revealed that tumor configuration, intestinal obstruction, serum carcinoembryonic antigen (CEA) concentration, T stage, N stage, and lymph node ratio were associated with disease-free survival of patients with stage III colorectal cancer (P < 0.05). Multivariate analysis showed that serum CEA concentration, T stage, and lymph node ratio were prognostic factors for disease-free survival (P < 0.05), whereas N stage failed to achieve significance (P = 0.664). We confirmed that lymph node ratio was a prognostic factor in stage III colorectal cancer and had a better prognostic value than did N stage. PMID- 22313595 TI - Nasopharyngeal carcinoma in Indonesia: epidemiology, incidence, signs, and symptoms at presentation. AB - Among all head and neck (H&N) cancers, nasopharyngeal carcinoma (NPC) represents a distinct entity regarding epidemiology, clinical presentation, biological markers, carcinogenic risk factors, and prognostic factors. NPC is endemic in certain regions of the world, especially in Southeast Asia, and has a poor prognosis. In Indonesia, the recorded mean prevalence is 6.2/100 000, with 13 000 yearly new NPC cases, but otherwise little is documented on NPC in Indonesia. Here, we report on a group of 1121 NPC patients diagnosed and treated at Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia between 1996 and 2005. We studied NPC incidence among all H&N cancer cases (n=6000) observed in that period, focusing on age and gender distribution, the ethnic background of patients, and the disease etiology. We also analyzed most prevalent signs and symptoms and staging of NPC patients at first presentation. In this study population, NPC was the most frequent H&N cancer (28.4%), with a male-to-female ratio of 2.4, and was endemic in the Javanese population. Interestingly, NPC appeared to affect patients at a relatively young age (20% juvenile cases) without a bimodal age distribution. Mostly, NPC initiated in the fossa of Rosenmuller and spreaded intracranially or locally as a mass in the head. Occasionally, NPC developed at the submucosal level spreading outside the anatomic limits of the nasopharynx. At presentation, NPC associated with hearing problems, serous otitis media, tinnitus, nasal obstruction, anosmia, bleeding, difficulty in swallowing and dysphonia, and even eye symptoms with diplopia and pain. The initial diagnosis is difficult to make because early signs and symptoms of NPC are not specific to the disease. Early-age Epstein-Barr virus (EBV) infection combined with frequent exposure to environmental carcinogenic co-factors is suggested to cause NPC development. Undifferentiated NPC is the most frequent histological type and is closely associated with EBV. Expression of the EBV-encoded latent membrane protein 1(LMP1) oncogene in biopsy material was compared between NPC patients of <30 years old and those of >=30 years old, matched for sex and tumor stage. Higher LMP1 expression in patients of <30 years old was observed, which was related to more locoregional progressivity. Increased medical awareness of prevailing early stage signs and symptoms coupled to use of EBV-related diagnostic tumor markers may lead to down-staging and timely treatment to improve survival of patients with this aggressive disease. PMID- 22313596 TI - Long-term molecular changes in WHO grade II astrocytomas following radiotherapy. AB - Monitoring the long-term radiotherapy-associated molecular changes in low-grade gliomas (LGGs) facilitates the understanding of LGG response to radiotherapy. In this study, we used immunohistochemistry to analyze the expression of Ki-67, tumor protein P53 (TP53), P21, and P27 in 8 paired WHO grade II astrocytoma samples. The interval between radiotherapy (RT) and the second surgery was more than 3 months in all cases. The average Ki-67 labeling index (LI) was 5.3% in pre RT samples and 11.54% in post-RT samples. Ki-67 LI was higher in the primary tumors that underwent malignant transformation observed at the second surgery after radiation. Post-RT Ki-67 LI decreased in 2 cases with an interval of less than 12 months between RT and the second surgery. TP53 expression was found in 3 out of 4 pre-RT samples with malignant transformation and in 1 out of 4 pre-RT samples without malignant transformation. Post-RT TP53 increased in 2 cases in which increased expression of P21 or P27 was also observed. Our study suggests that radiotherapy can inhibit WHO grade II astrocytoma proliferation as reflected by Ki-67 LI, but the effect attenuates with time. In addition, there is a tendency of malignant transformation for WHO grade II astrocytomas with a high Ki 67 level or TP53 expression in initial samples. PMID- 22313598 TI - Reconciling cyanobacterial fixed-nitrogen distributions and transport experiments with quantitative modelling. AB - Filamentous cyanobacteria growing in media with insufficient fixed nitrogen (fN) differentiate some cells into heterocysts, which fix nitrogen for the remaining vegetative cells. Transport studies have shown both periplasmic and cytoplasmic connections between cells that could transport fN along the filament. Two experiments have imaged fN distributions along filaments. In 1974, Wolk et al found a peaked concentration of fN at heterocysts using autoradiographic techniques. In contrast, in 2007, Popa et al used nanoSIMS to show large dips at the location of heterocysts, with a variable but approximately level distribution between them. With an integrated model of fN transport and cell growth, we recover the results of both Wolk et al and of Popa et al using the same model parameters. To do this, we account for immobile incorporated fN and for the differing durations of labelled nitrogen fixation that occurred in the two experiments. The variations seen by Popa et al are consistent with the effects of cell-by-cell variations of growth rates, and mask diffusive gradients. We are unable to rule out a significant amount of periplasmic fN transport. PMID- 22313597 TI - Functional roles and clinical values of insulin-like growth factor-binding protein-5 in different types of cancers. AB - Insulin-like growth factor-binding proteins(IGFBPs) are critical regulators of the mitogenic activity of insulin-like growth factors (IGFs). IGFBP5, one of these IGFBPs, has special structural features, including a nuclear transport domain, heparin-binding motif, and IGF/extracellular matrix/acid-labile subunit binding sites. Furthermore, IGFBP5 has several functional effects on carcinogenesis and even normal cell processes, such as cell growth, death, motility, and tissue remodeling. These biological effects are sometimes related with IGF (IGF-dependent effects) and sometimes not (IGF-independent effects). The functional role of IGFBP5 is most likely determined in a cell-type and tissue type specific manner but also depends on cell context, especially in terms of the diversity of interacting proteins and the potential for nuclear localization. Clinical findings show that IGFBP5 has the potential to be a useful clinical biomarker for predicting response to therapy and clinical outcome of cancer patients. In this review, we summarize the functional diversity and clinical importance of IGFBP5 in different types of cancers. PMID- 22313599 TI - Prognostic indicators for upper tract urothelial carcinoma after radical nephroureterectomy: the impact of lymphovascular invasion. AB - What's known on the subject? and What does the study add? In an array of urological and non-urological malignancies, lymphovascular invasion (LVI) is a pathological feature known to be associated with adverse outcomes for recurrence and survival. For some cancers, LVI has therefore been incorporated into American Joint Committee on Cancer TNM staging algorithms. This study presents an analysis of the impact of LVI in upper urinary tract urothelial carcinoma (UTUC) treated at our institution over a 20-year period. In addition to known associations with features of aggressive disease and overall survival, we were able to show that LVI-positive status upsets the TNM staging for UTUC. Namely, patients with superficial stage and LVI-positive disease have overall survival outcomes similar to those of patients with muscle-invasive LVI-negative carcinoma. Such evidence may support the addition of LVI to future TNM staging algorithms for UTUC. OBJECTIVE: To assess the impact of lymphovascular invasion (LVI) on the prognosis of patients with upper urinary tract urothelial cell carcinoma (UTUC) treated with radical nephroureterectomy (RNU). PATIENTS AND METHODS: The Columbia University Medical Center Urologic Oncology database was queried and 211 patients undergoing RNU for UTUC between 1990 and 2010 were identified. These cases were retrospectively reviewed, and the prognostic significance of relevant clinical and pathological variables was analysed using log-rank tests and Cox proportional hazards regression models. Actuarial survival curves were calculated using the Kaplan-Meier method. RESULTS: LVI was observed in 68 patients (32.2%). The proportion of LVI increased with advancing stage, high grade, positive margin status, concomitant carcinoma in situ, and lymph node metastases. The 5- and 10 year overall survival rates were 74.7% and 53.1% in the absence of LVI, and 35.7% and 28.6% in the presence of LVI, respectively. In multivariate analysis, age, race and LVI were independent predictors of overall survival. CONCLUSIONS: The presence of LVI on pathological review of RNU specimens was associated with worse overall survival in patients with UTUC. LVI status should be included in the pathological report for RNU specimens to help guide postoperative therapeutic options. With confirmation from large international studies, inclusion of LVI in the tumour-node-metastasis staging system for UTUC should be considered. PMID- 22313600 TI - Comprehensive report on prostate cancer misclassification by 16 currently used low-risk and active surveillance criteria. PMID- 22313601 TI - Isolation and culture of Sphaerothecum destruens from Sunbleak (Leucaspius delineatus) in the UK and pathogenicity experiments in Atlantic salmon (Salmo salar). AB - The sunbleak (Leucaspius delineatus), a cyprinid fish native to continental Europe and now established in the UK, is experiencing population decline which appears to be linked to the spread of the invasive Asian cyprinid (Pseudorasbora parva). A population of sunbleak in the UK has previously been identified as infected with S. destruens at low prevalence. Because Sphaerothaecum destruens has, on occasion, caused severe disease in cultured and wild salmonids the aim of this work was to establish laboratory cultures of S. destruens from sunbleak in the UK and use these cultures in challenge experiments to determine if the UK isolate of S. destruens from cyprinid species is a potential threat to Atlantic salmon (Salmo salar). The first isolation and culture of S. destruens in the UK and from a cyprinid species is described. Cultured S. destruens spores from sunbleak are infective to EPC, CHSE and FHM cells, replicating most rapidly in FHM and EPC cells. Spores can be induced to zoosporulate in water forming motile, uni-flagellated zoospores. Challenge experiments indicated the spores are able to replicate and disperse in Atlantic salmon and are associated with increased mortality (up to 90%) when injected intraperitonealy. PMID- 22313602 TI - Using the "reverse Warburg effect" to identify high-risk breast cancer patients: stromal MCT4 predicts poor clinical outcome in triple-negative breast cancers. AB - We have recently proposed a new model of cancer metabolism to explain the role of aerobic glycolysis and L-lactate production in fueling tumor growth and metastasis. In this model, cancer cells secrete hydrogen peroxide (H2O2), initiating oxidative stress and aerobic glycolysis in the tumor stroma. This, in turn, drives L-lactate secretion from cancer-associated fibroblasts. Secreted L lactate then fuels oxidative mitochondrial metabolism (OXPHOS) in epithelial cancer cells, by acting as a paracrine onco-metabolite. We have previously termed this type of two-compartment tumor metabolism the "Reverse Warburg Effect," as aerobic glycolysis takes place in stromal fibroblasts, rather than epithelial cancer cells. Here, we used MCT4 immuno-staining of human breast cancer tissue microarrays (TMAs; > 180 triple-negative patients) to directly assess the prognostic value of the "Reverse Warburg Effect." MCT4 expression is a functional marker of hypoxia, oxidative stress, aerobic glycolysis, and L-lactate efflux. Remarkably, high stromal MCT4 levels (score = 2) were specifically associated with decreased overall survival (< 18% survival at 10 y post-diagnosis). In contrast, patients with absent stromal MCT4 expression (score = 0), had 10-y survival rates of ~97% (p-value < 10 (-32) ). High stromal levels of MCT4 were strictly correlated with a loss of stromal Cav-1 (p-value < 10 (-14) ), a known marker of early tumor recurrence and metastasis. In fact, the combined use of stromal Cav-1 and stromal MCT4 allowed us to more precisely identify high-risk triple-negative breast cancer patients, consistent with the goal of individualized risk-assessment and personalized cancer treatment. However, epithelial MCT4 staining had no prognostic value, indicating that the "conventional" Warburg effect does not predict clinical outcome. Thus, the "Reverse Warburg Effect" or "parasitic" energy-transfer is a key determinant of poor overall patient survival. As MCT4 is a druggable-target, MCT4 inhibitors should be developed for the treatment of aggressive breast cancers, and possibly other types of human cancers. Similarly, we discuss how stromal MCT4 could be used as a biomarker for identifying high-risk cancer patients that could likely benefit from treatment with FDA-approved drugs or existing MCT-inhibitors (such as, AR-C155858, AR-C117977, and AZD-3965). PMID- 22313604 TI - The evolution of parasitoid fecundity: a paradigm under scrutiny. AB - An important assumption in insect parasitoid life-history theory is that, within parasitoid complexes (species assemblages associated with particular hosts), members attacking young host stages are more fecund than members targeting older ones. This hypothesis reflects the general trajectory of host survivorship curves: as a host cohort ages, availability to female parasitoids declines, as can the risk that the host - and the parasitoid offspring it carries - succumbs to extrinsic mortality. However, the analyses that provided empirical support for the hypothesis did not control for phylogeny. Using the original datasets, we use phylogenetically corrected analyses to test whether the results of the seminal study are upheld. Although we show those findings to be robust, the decline in fecundity could be a sampling artefact. We conclude that it would be unwise to assume the paradigm to be generally representative of natural parasitoid complexes. PMID- 22313603 TI - Autologous stromal vascular fraction therapy for rheumatoid arthritis: rationale and clinical safety. AB - Advancements in rheumatoid arthritis (RA) treatment protocols and introduction of targeted biological therapies have markedly improved patient outcomes, despite this, up to 50% of patients still fail to achieve a significant clinical response. In veterinary medicine, stem cell therapy in the form of autologous stromal vascular fraction (SVF) is an accepted therapeutic modality for degenerative conditions with 80% improvement and no serious treatment associated adverse events reported. Clinical translation of SVF therapy relies on confirmation of veterinary findings in targeted patient populations. Here we describe the rationale and preclinical data supporting the use of autologous SVF in treatment of RA, as well as provide 1, 3, 6, and 13 month safety outcomes in 13 RA patients treated with this approach. PMID- 22313605 TI - The effect of a fictitious peer on young children's choice of familiar v. unfamiliar low- and high-energy-dense foods. AB - The present experimental study was the first to investigate the impact of a remote (non-existent) peer on children's food choice of familiar v. unfamiliar low- and high-energy-dense food products. In a computer task, children (n 316; 50.3 % boys; mean age 7.13 (SD 0.75) years) were asked to choose between pictures of familiar and unfamiliar foods in four different choice blocks using the following pairs: (1) familiar v. unfamiliar low-energy-dense foods (fruits and vegetables), (2) familiar v. unfamiliar high-energy-dense foods (high sugar, salt and/or fat content), (3) familiar low-energy-dense v. unfamiliar high-energy dense foods and (4) unfamiliar low-energy-dense v. familiar high-energy-dense foods. Participants who were not in the control group were exposed to the food choices (either always the familiar or always the unfamiliar food product) of a same-sex and same-age fictitious peer who was supposedly completing the same task at another school. The present study provided insights into children's choices between (un)familiar low- and high-energy-dense foods in an everyday situation. The findings revealed that the use of fictitious peers increased children's willingness to try unfamiliar foods, although children tended to choose high energy-dense foods over low-energy-dense foods. Intervention programmes that use peer influence to focus on improving children's choice of healthy foods should take into account children's strong aversion to unfamiliar low-energy-dense foods as well as their general preference for familiar and unfamiliar high-energy-dense foods. PMID- 22313606 TI - A naturally occurring carotenoid, lutein, reduces PDGF and H2O2 signaling and compromised migration in cultured vascular smooth muscle cells. AB - BACKGROUND: Platelet-derived growth factor (PDGF) is a potent stimulator of growth and motility of vascular smooth muscle cells (VSMCs). Abnormalities of PDGF/PDGF receptor (PDGFR) are thought to contribute to vascular diseases and malignancy. We previously showed that a carotenoid, lycopene, can directly bind to PDGF and affect its related functions in VSMCs. In this study we examined the effect of the other naturally occurring carotenoid, lutein, on PDGF signaling and migration in VSMCs. METHODS: Western blotting was performed to examine PDGF and H2O2 signaling. Flowcytometry was used to determine PDGF binding to VSMCs. Fluorescence microscopy was performed to examine intracellular ROS production. Modified Boyden chamber system (Transwell apparatus) was used for migration assay. RESULTS: Lutein reduced PDGF signaling, including phosphorylation of PDGFR beta and its downstream protein kinases/enzymes such as phospholipase C-gamma, Akt, and mitogen-activated protein kinases (MAPKs). Although lutein possesses a similar structure to lycopene, it was striking that lutein inhibited PDGF signaling through a different way from lycopene in VSMCs. Unlike lycopene, lutein not only interacted with (bound to) PDGF but also interfered with cellular components. This was evidenced that preincubation of PDGF with lutein and treatment of VSMCs with lutein followed by removing of lutein compromised PDGF induced signaling. Lutein reduced PDGF-induced intracellular reactive oxygen species (ROS) production and attenuated ROS- (H2O2-) induced ERK1/2 and p38 MAPK activation. A further analysis indicated lutein could inhibit a higher concentration of H2O2-induced PDGFR signaling, which is known to act through an oxidative inhibition of protein tyrosine phosphatase. Finally, we showed that lutein functionally inhibited PDGF-induced VSMC migration, whereas its stereo isomer zeaxanthin did not, revealing a special action of lutein on VSMCs. CONCLUSIONS: Our study reveals a differential action mechanism of lutein from other reported caroteinoids and suggests a possible beneficial effect of lutein but not zeaxanthin on prevention of vascular diseases. PMID- 22313607 TI - Body mass index misclassification of obesity among community police officers. PMID- 22313608 TI - Global health summit-occupational health nurses' contributions to a healthy work force. PMID- 22313609 TI - International visitors and returning employees. AB - This article presents guidelines for possible exposures employees may encounter during travel or visitors may have encountered in their native country prior to entering the United States. PMID- 22313610 TI - Challenges and opportunities for occupational health nurses in Asia. AB - This article provides a brief overview of the effect of economic globalization on Asia, presents occupational health issues from select countries, and discusses challenges and opportunities for occupational health nurses. PMID- 22313611 TI - A comprehensive review of the healthy people 2020 occupational safety and health objectives: part 2. Tools for the occupational health nurse in goal attainment. AB - This is the second part of a two-part series introducing Healthy People 2020 and the foundational categories that are linked to overarching goals and corresponding measures of progress within the Healthy People 2020 initiative. The two articles together review the 10 objectives for occupational safety and health within the American workplace, provide a resource guide for occupational health nurses, and discuss MAP-IT, the suggested implementation format to reach the Healthy People 2020 goals. The articles are intended to inform occupational health nurses about the current agenda for safety and health of the U.S. work force as articulated in Healthy People 2020 and provide a foundation for better understanding the requirements of a safe work environment in 2020 and beyond. PMID- 22313613 TI - Traumatic nail gun injuries in the workplace. PMID- 22313614 TI - Development and validation of a screening instrument to assess the types and quality of foods served at home meals. AB - BACKGROUND: Although there is growing interest in assessing the home food environment, no easy-to-use, low cost tools exist to assess the foods served at home meals, making it difficult to assess the meal component of the food environment. The aim of this study was to develop and validate a user-friendly screener to assess the types of foods served at home meals. METHODS: Primary food preparing adults (n = 51) participated in a validation study in their own homes. Staff and participants independently completed a screener as participants cooked dinner. The screener assessed the types of foods offered, method(s) of preparation, and use of added fats. Two scale scores were created: 1) to assess offerings of foods in five food groups (meat and other protein, milk, vegetables, fruit, grains), 2) to assess the relative healthfulness of foods based on types offered, preparation method, and added fats. Criterion validity was assessed comparing staff and participant reports of individual foods (kappa (k)) and scale scores (Spearman correlations). RESULTS: Criterion validity was high between participants' and staffs' record of whether major food categories (meat and other protein, bread and cereal, salad, vegetables, fruits, dessert) were served (k = 0.79-1.0), moderate for reports of other starches (e.g., rice) being served (k = 0.52), and high for the Five Food Group and Healthfulness scale scores (r = 0.75 0.85, p < .001). CONCLUSIONS: This new meal screening tool has high validity and can be used to assess the types of foods served at home meals allowing a more comprehensive assessment of the home food environment. PMID- 22313615 TI - The ethics of pain clinical trials on persons lacking judgment ability: much to improve. AB - AIM: People lacking judgmental ability (newborn infants [NIs] and persons with mental impairment [PMI]) are reported to receive less analgesic treatments than people who can give adequate informed consent. We performed the present study to assess whether this also happens in clinical trials that should statutorily guarantee basic patients' rights. We examined those trials in which patients undergo painful minor procedures (PMP) because these procedures are frequent and severely stressful for NI and PMI. MATERIALS AND METHODS: We performed a Medline search to retrieve the studies published in 2009 and 2010, in which NI and PMI underwent PMP. RESULTS: We retrieved 46 studies that exposed NI to PMP; only in 14.2% of the studies, a validated analgesic treatment was administered to the control group. We retrieved only one article where PMP was performed in PMI for clinical reasons (venipuncture); in 13 more studies, pain was experimentally provoked by noxious stimuli such as heat, electricity, or arm mobilization. All these studies were not performed to evaluate a possible analgesic strategy but to assess PMI's pain responsiveness and no analgesia was used. CONCLUSION: PMI and NI enrolled in clinical trials as controls rarely receive analgesia; and few studies exist to find out analgesic treatments shaped on PMI's exigencies. These data raise concern about the actual guarantees for persons lacking judgmental ability enrolled in potentially painful trials. We also recommend more effort to find out analgesic treatments tailored to the specific exigencies of PMI. PMID- 22313616 TI - Prognostic significance of Bacillus Calmette-Guerin failure classification in non muscle-invasive bladder cancer. AB - What's known on the subject? and What does the study add? Adjuvant intravesical BCG therapy is the most effective regimen for non-muscle-invasive bladder cancer. Previously, patients who experienced recurrences after BCG therapy tended to be lumped together as patients with 'BCG failure', but BCG failure was defined inconsistently in each study and several studies indicated that patients with a particular pattern of BCG failure had a worse prognosis. We divided patients with BCG failure into four groups, which were based mainly on the responsiveness to BCG therapy and duration until tumour recurrence. Patients in the BCG-refractory group, in particular, had a higher risk for subsequent stage progression and disease-specific death over a long duration compared with patients in the other BCG-failure groups. As the definitions of BCG failure used to date have been decidedly heterogeneous, we recommend that standardized treatment decisions, protocols and recommendations be established according to individual BCG failure patterns. OBJECTIVE: To investigate the differences in the clinical features and subsequent stage progression and disease-specific survival among patients with Bacillus Calmette-Guerin (BCG) failure, after dividing these patients into BCG refractory, -resistant, -relapsing, and -intolerant groups. PATIENTS AND METHODS: We identified 173 patients with initial BCG failure from 521 patients who had undergone induction BCG therapy for non-muscle-invasive bladder cancer, excluding CIS, between 1987 and 2009. Patients were stratified into four BCG-failure groups, and each prognostic outcome was evaluated. RESULTS: Median follow-up period from initial BCG failure was 4.7 years. A total of 42 patients (24.3%) were stratified into the BCG-refractory, three (1.7%) into the BCG-resistant, 106 (61.3%) into the BCG-relapsing, and 22 (12.7%) into the BCG-intolerant group. Twenty-four patients (13.9%) experienced stage progression during follow-up. Multivariate analysis showed that pathological G3 at BCG failure (P = 0.014; risk ratio 2.84) and BCG-refractory (P < 0.001; risk ratio 4.68) were independent predictors for stage progression. The 10-year progression-free survival rates were 53.2%, 91.1% and 93.8% in the BCG-refractory, BCG-relapsing and BCG intolerant groups, respectively. The stage progression rate was higher in the BCG refractory than in the BCG-relapsing (P < 0.001) and BCG-intolerant (P = 0.007) groups. Similarly, the 10-year disease-specific survival rate in the BCG refractory group was significantly worse than those in the other BCG failure groups (P < 0.001). CONCLUSIONS: Stratification of BCG failure into the above mentioned four groups can identify patients with BCG-failure in terms of their prognosis. The potential risk for critical adverse events was higher in the BCG refractory group than in the other BCG-failure groups, despite the fact that patients in each group all underwent induction BCG therapy, therefore, treatment decisions, protocols and recommendations should be established based on each individual BCG-failure pattern. PMID- 22313617 TI - Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder. AB - BACKGROUND: Converging neuroimaging research suggests altered emotion neurocircuitry in individuals with posttraumatic stress disorder (PTSD). Emotion activation studies in these individuals have shown hyperactivation in emotion related regions, including the amygdala and insula, and hypoactivation in emotion regulation regions, including the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). However, few studies have examined patterns of connectivity at rest in individuals with PTSD, a potentially powerful method for illuminating brain network structure. METHODS: Using the amygdala as a seed region, we measured resting-state brain connectivity using 3 T functional magnetic resonance imaging in returning male veterans with PTSD and combat controls without PTSD. RESULTS: Fifteen veterans with PTSD and 14 combat controls enrolled in our study. Compared with controls, veterans with PTSD showed greater positive connectivity between the amygdala and insula, reduced positive connectivity between the amygdala and hippocampus, and reduced anticorrelation between the amygdala and dorsal ACC and rostral ACC. LIMITATIONS: Only male veterans with combat exposure were tested, thus our findings cannot be generalized to women or to individuals with non-combat related PTSD. CONCLUSION: These results demonstrate that studies of functional connectivity during resting state can discern aberrant patterns of coupling within emotion circuits and suggest a possible brain basis for emotion-processing and emotion-regulation deficits in individuals with PTSD. PMID- 22313618 TI - Rapid simulation of protein motion: merging flexibility, rigidity and normal mode analyses. AB - Protein function frequently involves conformational changes with large amplitude on timescales which are difficult and computationally expensive to access using molecular dynamics. In this paper, we report on the combination of three computationally inexpensive simulation methods--normal mode analysis using the elastic network model, rigidity analysis using the pebble game algorithm, and geometric simulation of protein motion--to explore conformational change along normal mode eigenvectors. Using a combination of ElNemo and First/Froda software, large-amplitude motions in proteins with hundreds or thousands of residues can be rapidly explored within minutes using desktop computing resources. We apply the method to a representative set of six proteins covering a range of sizes and structural characteristics and show that the method identifies specific types of motion in each case and determines their amplitude limits. PMID- 22313619 TI - High cold tolerance through four seasons and all free-living stages in an ectoparasite. AB - Off-host stages of temperate parasites must cope with low temperatures. Cold tolerance is often highest in winter, as a result of diapause and cold acclimation, and low during the active summer stages. In some blood-feeding ectoparasites, offspring provisioning determines cold tolerance through all the non-feeding, off-host stages. Large size increases survival in the cold, but so far seasonal variation in within-female offspring size has not been associated with offspring cold tolerance. The deer ked (Lipoptena cervi) reproduces on cervids from autumn to spring. Newborn pupae drop off the host, facing frosts without any acclimation. We examined cold tolerance through 4 seasons and from birth to adulthood by means of short- and long-term frost exposure. We expected females to produce more tolerant offspring in winter than in spring. Large spring pupae survived prolonged frosts better than did small winter pupae. Thus more tolerant offspring were not produced when the temperature outside the host is at its lowest. Unexpectedly, the freezing points were -20 degrees C or below all year round. We showed that high cold tolerance is possible without acclimation regardless of life stage, which presumably correlates with other survival characteristics, such as the starvation resistance of free-living ectoparasites. PMID- 22313620 TI - Exploring learning outcomes of school-based health promotion--a multiple case study. AB - This paper discusses the findings of a multiple case study of a European health promotion project--Shape Up--a school-community approach to influencing determinants of a healthy and balanced growing up. The project sought to develop children's capacity to critically explore and act to improve health-related conditions at school and in the community. The aim of the study is to explore learning outcomes, defined as changes in pupils' action competence, of the Shape Up project. Further, the study addresses the interplay between the project's methodology and contextual factors related to its implementation and its impact on learning outcomes. Case study research was conducted in five schools in five different countries. Data were generated through document analysis, interviews and observations. A cross-case analysis was conducted, inspired by the Context Mechanism-Outcome analytical framework proposed by Pawson and Tilley (1997). Changes related to pupils' knowledge, skills, visions, critical thinking and decision making, experience with taking action and a realization that they can change things stand out as essential for the pupils' developing sense of action competence. Two different implementation forms of the project's methodological approach were identified across the five cases, both conducive to changes in pupils' action competence. PMID- 22313621 TI - Pre-exercise screening and health coaching in CHD secondary prevention: a qualitative study of the patient experience. AB - Secondary prevention programmes can be effective in reducing morbidity and mortality from coronary heart disease (CHD). In particular, UK guidelines, including those from the Department of Health, emphasize physical activity. However, the effects of secondary prevention programmes with an exercise component are moderate and uptake is highly variable. In order to explore patients' experiences of a pre-exercise screening and health coaching programme (involving one-to-one consultations to support exercise behaviour change), semi structured telephone interviews were undertaken with 84 CHD patients recruited from primary care. The interviews focused on patients' experiences of the intervention including referral and any recommendations for improvement. A thematic analysis of transcribed interviews showed that the majority of patients were positive about referral. However, patients also identified a number of barriers to attending and completing the programme, including a belief they were sufficiently active already, the existence of other health problems, feeling unsupported in community-based exercise classes and competing demands. Our findings highlight important issues around the choice of an appropriate point of intervention for programmes of this kind as well as the importance of appropriate patient selection, suggesting that the effectiveness of health coaching may be under-reported as a result of including patients who are not yet ready to change their behaviours. PMID- 22313622 TI - Management of severe blunt renal trauma in adult patients: a 10-year retrospective review from an emergency hospital. AB - What's known on the subject? and What does the study add? Immediate surgery for major renal truma has led to a high rate of nephrectomy in comparison with an expectant management. We reviewed our case material on the management of severe blunt renal trauma in adults with emphasis on conservative management. Only shattered kidneys and pedicle avulsion required immediate surgery. OBJECTIVE: To review retrospectively the management of major blunt renal truma in adult patients admitted to our level I trauma centre. PATIENTS AND METHODS: Among 1460 blunt abdominal trauma cases collected from January 2001 to December 2010, 221 (15%) affected the kidneys. All patients, except seven who needed immediate laparotomy, underwent a computed tomography scan to stage the injuries. Renal injuries were graded according to the American Association for the Surgery of Trauma Grading System; grade 4 and 5 injuries were subclassified based on vascular or parenchymal injury. RESULTS: Only 45/221 patients (20%) suffered major blunt renal trauma (21 grade 3, 18 grade 4 and six grade 5); 43% of the patients had associated lesions and 77% had gross haematuria. Nephrectomy rates were 9% for grade 3, 22% for grade 4 and 83% for grade 5 with an exploration rate of 26% for major renal trauma. CONCLUSIONS: Conservative management of grade 3-5 blunt renal trauma in haemodynamically stable patients yields more favourable results with high renal salvage rate. Grade 5 injuries still result in a nephrectomy rate of more than 80%. The absence of data on long-term outcomes and a potential inclusion bias due to the retrospective nature of the data represent major limitations of this review. PMID- 22313624 TI - The neural manifestation of the word concreteness effect: an electrical neuroimaging study. AB - Previous studies have provided controversial evidence about the way in which words with different degrees of concreteness are represented in the brain. The aim of the present study was to investigate whether the processing of abstract vs. concrete words differently affected the timing and topographical distribution of ERP components. Participants were engaged in a lexical decision task (word/non word discrimination) while EEG was recorded from 128 scalp sites. Reaction times (RTs) to words were faster than RTs to pseudowords. Words were discriminated from pseudowords since larger N2 responses to words than to pseudowords were observed over the left occipito-temporal areas at 300 ms post-stimulus. Concrete words and abstract words were discriminated as early as 350 ms post-stimulus, with larger responses to concrete than to abstract words over the mesial occipital regions. Concreteness-related ERP differences were also observed in the amplitudes of the later anterior LP component (between 370 and 570 ms), with larger responses to abstract words than to concrete words. The LORETA source localization technique was also applied to identify the intra-cranial generators of surface potentials reflecting lexico-semantic processing. Results showed that words (both abstract and concrete) were associated with a stronger activation of the left fusiform gyrus and the left temporal cortex, as compared to pseudowords. Concrete word processing was associated with a stronger activation of the left extrastriate visual areas (namely BA 18 and BA 19) as compared to abstract word processing. By revealing the neural markers of the concreteness effect, our study contributes to the understanding of the neurogenesis of verbal semantic knowledge impairments and the incidence of these impairments in clinical populations. PMID- 22313623 TI - The impact of IL28B genotype on the gene expression profile of patients with chronic hepatitis C treated with pegylated interferon alpha and ribavirin. AB - BACKGROUND: Recent studies of CH-C patients have demonstrated a strong association between IL28B CC genotype and sustained virologic response (SVR) after PEG-IFN/RBV treatment. We aimed to assess whether IL28B alleles rs12979860 genotype influences gene expression in response to PEG-IFN/RBV in CH-C patients. METHODS: Clinical data and gene expression data were available for 56 patients treated with PEG-IFN/RBV. Whole blood was used to determine IL28B genotypes. Differential expression of 153 human genes was assessed for each treatment time point (Days: 0, 1, 7, 28, 56) and was correlated with IL28B genotype (IL28B C/C or non-C/C) over the course of the PEG-IFN/RBV treatment. Genes with statistically significant changes in their expression at each time point were used as an input for pathway analysis using KEGG Pathway Painter (KPP). Pathways were ranked based on number of gene involved separately per each study cohort. RESULTS: The most striking difference between the response patterns of patients with IL28B C/C and T* genotypes during treatment, across all pathways, is a sustained pattern of treatment-induced gene expression in patients carrying IL28B C/C. In the case of IL28B T* genotype, pre-activation of genes, the lack of sustained pattern of gene expression or a combination of both were observed. This observation could potentially provide an explanation for the lower rate of SVR observed in these patients. Additionally, when the lists of IL28B genotype specific genes which were differentially expressed in patients without SVR were compared at their baseline, IRF2 and SOCS1 genes were down-regulated regardless of patients' IL28B genotype. Furthermore, our data suggest that CH-C patients who do not have the SOCS1 gene silenced have a better chance of achieving SVR. Our observations suggest that the action of SOCS1 is independent of IL28B genotype. CONCLUSIONS: IL28B CC genotype patients with CH-C show a sustained treatment induced gene expression profile which is not seen in non-CC genotype patients. Silencing of SOCS1 is a negative and independent predictor of SVR. These data may provide some mechanistic explanation for higher rate of SVR in IL28B CC patients who are treated with PEG-IFN/RBV. PMID- 22313625 TI - Deer (Cervus elaphus) antler extract suppresses adhesion and migration of endometriotic cells and regulates MMP-2 and MMP-9 expression. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Deer antler has been used for centuries as medicine for a wide range of health problems, including various women's diseases. However, there is a safety concern related to its use in hormone-sensitive conditions, such as breast cancer and endometriosis. In the present study, we investigated the effect of deer (Cervus elaphus) antler extract (DAE) on adhesion and migration of human endometriotic cells. MATERIALS AND METHODS: Adhesion, wound-healing, and transwell migration assays were performed in endometriotic cells 11Z and 12Z. Expression of matrix metalloproteinase (MMP)-2, MMP-9, TNF alpha, and IL-6 were measured by real-time RT-PCR and Western blot analysis. RESULTS: DAE (50 and 100MUg/ml) decreased the adhesion of 11Z and 12Z cells on peritoneal mesothelial Met5-A cells. Wound-healing and transwell migration assays revealed that DAE (50 and 100MUg/ml) inhibited migration in 11Z and 12Z cells. It was further demonstrated that treatment with DAE (50 and 100MUg/ml) significantly decreased the levels of MMP-2, MMP-9, TNF-alpha, and IL-6. CONCLUSIONS: These results indicate that DAE is a potential anti-endometriotic agent to inhibit the adhesion and migration of endometrial cells through the suppression of various related molecules. PMID- 22313626 TI - Omics and its potential impact on R&D and regulation of complex herbal products. AB - In traditional Chinese medicine (TCM), multicomponent and principally plant derived drugs are used for disease prevention, symptom amelioration and treatment in a personalized manner. Because of their complex composition and consequent multiple targets and treatment objectives, the application of omics techniques and other integrative approaches seems inherently appropriate and even necessary for the demonstration of their potential preclinical and clinical safety and efficacy. This perspectives article provides proposals for the application of omics methods to the investigation of complex herbal products (CHP),(1) including Chinese herbal medicines (CHM), both in vitro and in vivo, for preclinical and clinical toxicity, pharmacokinetics, pharmacodynamics and efficacy tests. Ultimately, such approaches could aid regulatory scrutiny and potential acceptance, although currently there is no regulatory requirement of omics-based data in any submitted dossier to any regulatory agency, including for conventional drugs and CHP. However, it has been acknowledged that such studies are being increasingly performed, and almost surely will eventually be included into regulatory submission dossiers, possibly initially as supplementary materials. Specifically for CHM and CHP, omics can play a role both in determining product composition and its variability and in monitoring biological effects in carefully selected platforms. Predicting the future is difficult, but it seems possible that regulatory acceptance of omics techniques and a systems biology approach for the study of TCM, CHM and CHP will not be long delayed. It is expected that current studies and plans employing omics techniques and other integrative approaches will prove to be positive and informative. PMID- 22313627 TI - Effect of an alkaloidal fraction of Tabernaemontana elegans (Stapf.) on selected micro-organisms. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Bacterial infections remain a significant threat to human health. Due to the emergence of widespread antibiotic resistance, development of novel antibiotics is required in order to ensure that effective treatment remains available. There are several reports on the ethnomedical use of Tabernaemontana elegans pertaining to antibacterial activity. AIM OF THE STUDY: The aim of this study was to isolate and identify the fraction responsible for the antimicrobial activity in Tabernaemontana elegans (Stapf.) root extracts. MATERIALS AND METHODS: The active fraction was characterized by thin layer chromatography (TLC) and gas chromatography-mass spectrometry (GC-MS). Antibacterial activity was determined using the broth micro-dilution assay and antimycobacterial activity using the BACTEC radiometric assay. Cytotoxicity of the crude extract and fractions was assessed against primary cell cultures; lymphocytes and fibroblasts; as well as a hepatocarcinoma (HepG2) and macrophage (THP-1) cell line using the Neutral Red uptake and MTT assays. RESULTS: The crude root extracts were found to contain a high concentration of alkaloids (1.2%, w/w). GC-MS analysis identified the indole alkaloids, voacangine and dregamine, as major components. Antibacterial activity was limited to the Gram-positive bacteria and Mycobacterium species, with MIC values in the range of 64-256MUg/ml. When combined with antibiotics, additive antibacterial effects were observed. Marked cytotoxicity to all cell lines tested was evident in the MTT and Neutral Red uptake assays, with IC(50) values <9.81MUg/ml. CONCLUSIONS: This study confirms the antibacterial activity of Tabernaemontana elegans and supports its potential for being investigated further for the development of a novel antibacterial compound. PMID- 22313628 TI - Molecular characterization of Neisseria meningitidis B:NT:P1.14/162 clonal complex responsible of invasive meningococcal disease in the north of Italy. AB - The molecular characteristics of 14 B:NT:P1.14 Neisseria meningitidis isolates, collected from 2007 through 2010 in Italy, have been investigated. The B:NT:P1.14 phenotype has only more recently been identified in our country, mainly associated with clonal complex CC162, which is rare in Italy. PMID- 22313629 TI - Prevalence of Bordetella pertussis and Bordetella parapertussis infections in Tunisian hospitalized infants: results of a 4-year prospective study. AB - The prevalence of pertussis in Tunisia remains undetermined essentially because of the unavailability of a basic laboratory diagnostic service. Specific diagnostic tools were applied for the first time in a Tunisian prospective study in order to get a first estimation of the prevalence of Bordetella pertussis/parapertussis infections and to evaluate their use to determine the epidemiologic characteristics of these infections in Tunisian infants. Between 2007 and 2011, a total of 626 samples from 599 infants aged <1 year with and without pertussoid cough were investigated for the presence of B. pertussis/parapertussis using culture and real-time polymerase chain reaction (PCR). The real-time PCR (RT-PCR) targets include IS481 commonly found in B. pertussis, B. bronchiseptica, and B. holmesii; IS1001 specific of B. parapertussis, in combination with the pertussis toxin promoter region gene (ptx) of B. pertussis; and the recA gene specific of B. holmesii. When possible, patients' household contacts provided nasopharyngeal aspirates (NPAs) for RT-PCR detection of B. pertussis/parapertussis or single-serum samples for anti-PT IgG quantification. All except 1 NPAs were negative by conventional culture, whereas PCR gave positive signals for 126 specimens (21%): B. pertussis, B. parapertussis, and Bordetella spp. were detected in 82%, 6%, and 4% of the samples, respectively. The simultaneous presence of B. pertussis and B. parapertussis was noted in 8% of the cases. Pertussis was reported throughout the year with a peak during the summer of the year 2009. The prevalence of Bordetella infection was 20% between 2007 and 2011. Most of these cases corresponded to patients younger than 6 months who received <3 doses of pertussis vaccine. Among the household contacts enrolled in the study, mothers seemed to be the likely source of infection. This study showed that pertussis is still prevalent in Tunisia and that the disease remains a public health problem affecting not only infants but also adults. Given this situation, sensitive and specific laboratory tests are needed to improve the accuracy of pertussis diagnosis. PMID- 22313630 TI - FtsZ rings and helices: physical mechanisms for the dynamic alignment of biopolymers in rod-shaped bacteria. AB - In many bacterial species, the protein FtsZ forms a cytoskeletal ring that marks the future division site and scaffolds the division machinery. In rod-shaped bacteria, most frequently membrane-attached FtsZ rings or ring fragments are reported and occasionally helices. By contrast, axial FtsZ clusters have never been reported. In this paper, we investigate theoretically how dynamic FtsZ aggregates align in rod-shaped bacteria. We study systematically different physical mechanisms that affect the alignment of FtsZ polymers using a computational model that relies on autocatalytic aggregation of FtsZ filaments at the membrane. Our study identifies a general tool kit of physical and geometrical mechanisms by which rod-shaped cells align biopolymer aggregates. Our analysis compares the relative impact of each mechanism on the circumferential alignment of FtsZ as observed in rod-shaped bacteria. We determine spontaneous curvature of FtsZ polymers and axial confinement of FtsZ on the membrane as the strongest factors. Including Min oscillations in our model, we find that these stabilize axial and helical clusters on short time scales, but promote the formation of an FtsZ ring at the cell middle at longer times. This effect could provide an explanation to the long standing puzzle of transiently observed oscillating FtsZ helices in Escherichia coli cells prior to cell division. PMID- 22313631 TI - Impact of long-term treatment of onchocerciasis with ivermectin in Kaduna State, Nigeria: first evidence of the potential for elimination in the operational area of the African Programme for Onchocerciasis Control. AB - BACKGROUND: Onchocerciasis can be effectively controlled as a public health problem by annual mass drug administration of ivermectin, but it was not known if ivermectin treatment in the long term would be able to achieve elimination of onchocerciasis infection and interruption of transmission in endemic areas in Africa. A recent study in Mali and Senegal has provided the first evidence of elimination after 15-17 years of treatment. Following this finding, the African Programme for Onchocerciasis Control (APOC) has started a systematic evaluation of the long-term impact of ivermectin treatment projects and the feasibility of elimination in APOC supported countries. This paper reports the first results for two onchocerciasis foci in Kaduna, Nigeria. METHODS: In 2008, an epidemiological evaluation using skin snip parasitological diagnostic method was carried out in two onchocerciasis foci, in Birnin Gwari Local Government Area (LGA), and in the Kauru and Lere LGAs of Kaduna State, Nigeria. The survey was undertaken in 26 villages and examined 3,703 people above the age of one year. The result was compared with the baseline survey undertaken in 1987. RESULTS: The communities had received 15 to 17 years of ivermectin treatment with more than 75% reported coverage. For each surveyed community, comparable baseline data were available. Before treatment, the community prevalence of O. volvulus microfilaria in the skin ranged from 23.1% to 84.9%, with a median prevalence of 52.0%. After 15 to 17 years of treatment, the prevalence had fallen to 0% in all communities and all 3,703 examined individuals were skin snip negative. CONCLUSIONS: The results of the surveys confirm the finding in Senegal and Mali that ivermectin treatment alone can eliminate onchocerciasis infection and probably disease transmission in endemic foci in Africa. It is the first of such evidence for the APOC operational area. PMID- 22313632 TI - Phenylalanine as a hydroxyl radical-specific probe in pyrite slurries. AB - The abundant iron sulfide mineral pyrite has been shown to catalytically produce hydrogen peroxide (H2O2) and hydroxyl radical (.OH) in slurries of oxygenated water. Understanding the formation and fate of these reactive oxygen species is important to biological and ecological systems as exposure can lead to deleterious health effects, but also environmental engineering during the optimization of remediation approaches for possible treatment of contaminated waste streams. This study presents the use of the amino acid phenylalanine (Phe) to monitor the kinetics of pyrite-induced .OH formation through rates of hydroxylation forming three isomers of tyrosine (Tyr) - ortho-, meta-, and para Tyr. Results indicate that about 50% of the Phe loss results in Tyr formation, and that these products further react with .OH at rates comparable to Phe. The overall loss of Phe appeared to be pseudo first-order in [Phe] as a function of time, but for the first time it is shown that initial rates were much less than first-order as a function of initial substrate concentration, [Phe]o. These results can be rationalized by considering that the effective concentration of .OH in solution is lower at a higher level of reactant and that an increasing fraction of .OH is consumed by Phe-degradation products as a function of time. A simplified first-order model was created to describe Phe loss in pyrite slurries which incorporates the [Phe]o, a first-order dependence on pyrite surface area, the assumption that all Phe degradation products compete equally for the limited supply of highly reactive .OH, and a flux that is related to the release of H2O2 from the pyrite surface (a result of the incomplete reduction of oxygen at the pyrite surface). An empirically derived rate constant, Kpyr, was introduced to describe a variable .OH-reactivity for different batches of pyrite. Both the simplified first-order kinetic model, and a more detailed numerical simulation, yielded results that compare well to the observed kinetic data describing the effects of variations in concentrations of both initial Phe and pyrite. This work supports the use of Phe as a useful probe to assess the formation of .OH in the presence of pyrite, and its possible utility for similar applications with other minerals. PMID- 22313633 TI - Imbalanced matrix metalloproteinases in cardiovascular complications of end-stage kidney disease: a potential pharmacological target. AB - End-stage kidney disease (ESKD) is a major health problem associated with very high morbidity and mortality secondary to cardiovascular complications, especially in ESKD patients on dialysis. Therefore, exploring key mechanisms underlying cardiovascular alterations associated with ESKD may offer reasonable pharmacological targets that may benefit these patients. Imbalanced matrix metalloproteinases (MMP) activities have been implicated in many cardiovascular diseases, and growing evidence now indicates that excessive MMP activities contribute to cardiovascular complications in ESKD patients. However, there is no study on the effects of MMP inhibitors (MMPIs) in such patients. MMPIs may prevent against the vascular and cardiac changes associated with ESKD. In this MiniReview, we aimed at reviewing current evidence supporting the idea that pharmacological inhibition of imbalanced MMP activities in ESKD may decrease the morbidity and mortality associated with cardiovascular complications in ESKD patients. However, MMPs have variable effects during different phases of kidney disease, and therefore optimal timing for MMP inhibition during a disease process may vary significantly and is largely undetermined. While current research shows that MMPs play a role in the pathogenesis of the cardiovascular alterations found in ESKD patients, clinical studies are required to validate the idea of using MMPIs in ESKD. PMID- 22313634 TI - Letter to the editor: quality of mental health information on Wikipedia. PMID- 22313635 TI - Targeting cytomegalovirus-infected cells using T cells armed with anti-CD3 * anti CMV bispecific antibody. AB - Human cytomegalovirus (CMV) reactivation and infection can lead to poor outcomes after allogeneic stem cell transplantation. We hypothesized that anti-CD3 activated T cells (ATCs) armed with chemically heteroconjugated anti-CD3 * polyclonal anti-CMV bispecific antibody (CMVBi) will target and eliminate CMV infected cells. Arming doses of CMVBi as low as 0.01 ng/10(6) ATCs was able to mediate specific cytotoxicity (SC) directed at CMV-infected target cells significant above unarmed ATCs at mutiplicities of infection (MOI) between 0.01 and 1. At effector-to-target ratios (E:T) of 25:1, 12.5:1, 6.25:1, and 3.125:1, armed ATCs significantly enhanced killing of CMV-infected targets compared with unarmed ATCs. At an MOI of 1.0, the mean % SC directed at CMV-infected targets cells for CMVBi-armed ATCs at E:T of 3.12, 6.25, and 12.5 were 79%, 81%, and 82%, respectively; whereas the mean % SC for unarmed ATCs at the same E:T were all <20%. ATCs, Cytogam((r)), or CMVBi alone did not lyse uninfected or CMV-infected targets. Co-cultures of CMVBi-armed ATCs with CMV-infected targets induced cytokine and chemokine release from armed ATCs. This nonmajor histocompatibility complex restricted strategy for targeting CMV could be used to prevent or treat CMV infections after allogeneic stem cell transplantation or organ transplantation. PMID- 22313636 TI - Bortezomib induces apoptosis and growth suppression in human medulloblastoma cells, associated with inhibition of AKT and NF-KB signaling, and synergizes with an ERK inhibitor. AB - Medulloblastoma is the most common brain tumor in children. Here, we report that bortezomib, a proteasome inhibitor, induced apoptosis and inhibited cell proliferation in two established cell lines and a primary culture of human medulloblastomas. Bortezomib increased the release of cytochrome c to cytosol and activated caspase-9 and caspase-3, resulting in cleavage of PARP. Caspase inhibitor (Z-VAD-FMK) could rescue medulloblastoma cells from the cytotoxicity of bortezomib. Phosphorylation of AKT and its upstream regulator mTOR were reduced by bortezomib treatment in medulloblastoma cells. Bortezomib increased the expression of Bad and Bak, pro-apoptotic proteins, and p21Cip1 and p27Kip1, negative regulators of cell cycle progression, which are associated with the growth suppression and induction of apoptosis in these tumor cells. Bortezomib also increased the accumulation of phosphorylated IKBalpha, and decreased nuclear translocation of NF-KB. Thus, NF-KB signaling and activation of its downstream targets are suppressed. Moreover, ERK inhibitors or downregulating ERK with ERK siRNA synergized with bortezomib on anticancer effects in medulloblastoma cells. Bortezomib also inhibited the growth of human medulloblastoma cells in a mouse xenograft model. These findings suggest that proteasome inhibitors are potentially promising drugs for treatment of pediatric medulloblastomas. PMID- 22313637 TI - Lack of AKT activation in lung cancer cells with EGFR mutation is a novel marker of cetuximab sensitivity. AB - Epidermal growth factor receptor (EGFR) mutation is the best marker of sensitivity to the EGFR tyrosine kinase inhibitor gefitinib, but a marker for the anti-EGFR antibody cetuximab has not been identified in lung cancer. The present study investigated markers for sensitivity to cetuximab. Sensitivity to cetuximab and gefitinib was compared with EGFR expression, EGFR and KRAS mutation, and EGFR gene copy numbers in lung cancer cell lines. We also studied the effect of these agents on the activation of EGFR, ERK, AKT, and STAT3 in cetuximab-sensitive and resistant cell lines. We found one cetuximab-sensitive cell line with EGFR mutation among 19 lung cancer cell lines. Analysis of molecules downstream from EGFR revealed that AKT phosphorylation was suppressed in this cell line. Augmentation of AKT phosphorylation by transfection of a plasmid induced resistance to cetuximab. Acquisition of cetuximab resistance was associated with AKT activation in this cell line, while pharmacological inhibition of AKT markedly enhanced the growth inhibitory effect of cetuximab. Dephosphorylation of AKT in association with EGFR mutation is a candidate marker for sensitivity to cetuximab, and combined use of an AKT pathway inhibitor with cetuximab could be a novel therapeutic strategy for lung cancer. PMID- 22313638 TI - Granulocyte-colony stimulating factor promotes proliferation, migration and invasion in glioma cells. AB - Sustaining proliferative signaling is one of the hallmarks of cancer. Granulocyte colony stimulating factor (G-CSF), a hematopoietic growth factor that controls proliferation and differentiation of neural stem cells, may contribute to the development of glioma. In the present study, we evaluated the expression of G-CSF and its receptor (G-CSFR) in various grades of glioma samples and primary cell culture derived from a glioblastoma patient as well as different human glioma cell lines. We showed that G-CSF and G-CSFR were widely expressed by glioma samples, primary glioma cell culture and glioma cell lines. The expression levels of G-CSF and G-CSFR were not significantly different between different grades of glioma. G-CSF promoted proliferation, migration and invasion of glioma cells. Neutralization of G-CSFR with its antibody inhibited growth and metastasis of glioma cells in vitro. We also showed that activation of signal transducer and activator transcription 3 (STAT 3) as well as expression of several of its downstream effectors was regulated by G-CSF. Taken together, the present results suggest that G-CSF contributes to glioma progression that may be linked to glioma genesis and recurrence. PMID- 22313639 TI - Identification of Nkx2-3 and TGFB1I1 expression levels as potential biomarkers to predict the effects of FOLFOX4 chemotherapy. AB - This study was designed to detect global gene expressions of primary advanced colorectal cancer (ACC) patients who have undergone FOLFOX4 chemotherapy and screen valuable biomarkers to predict the effects of chemotherapy. Samples from primary ACC patients who have undergone FOLFOX4 chemotherapy were collected. Their chemotherapy effects were evaluated and divided into chemotherapy sensitive group (experimental group) and non-sensitive group (control group). Cancerous tissue gene expression profiles were detected by chip technology. Two groups with differentially expressed genes were screened by cluster analysis and significance analysis of microarrays (SAM). Valuable biomarkers were screened by bioinformatics analysis. Immunohistochemical analysis was performed to characterize the pattern of Nkx2-3 and TGFB1I1 expression. Nkx2-3 and TGFB1I1 signal log ratio were used Receiver Operating Characteristic (ROC) analyses to calculate its own predicting accuracy. Thirty cases were divided into experimental group (13 cases) and control group (17 cases). There was evident difference in the tumor cell biology states of the two groups; that is, 25 ESTs (21 genes) were upregulated and 5 ESTs (5 genes) were downregulated. Nkx2-3 protein was observed on the nucleus of the cancer cells and TGFB1I1 protein was observed on the nucleus and cytoplasm of the cancer cells in experimental group. Their prediction accuracies were 85.3% and 76.7% respectively. Nkx2-3 and TGFB1I1 expressions in control group are very low, but highly expressed in the experimental group; Nkx2-3 and TGFB1I1 may be classified as valuable biomarkers, as these can predict the effects of primary ACC patients who will undergo FOLFOX4. PMID- 22313640 TI - Hepatic fibrosis imaging: trends and feasibility. PMID- 22313641 TI - Influence of serotonergic 5-HT2C receptor antagonist mesulergine in the reversal of memory deficits induced by mCPP. AB - OBJECTIVE: To determine the effect of non-selective 5-HT2C antagonist mesulergine and 5-HT2C agonist mCPP (metachlorophenylpiperazine) on learning acquisition (LA), short-term memory (STM) and long-term memory (LTM). STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Department of Biochemistry, University of Karachi, from December 2009 to June 2010. METHODOLOGY: Twenty-four male albino Wistar rats were used in this study. The agonist and antagonist (mCPP and mesulergine) were injected intraperitoneally at a dose 3.0 mg/kg in volumes of 1 ml/kg. Control animals were injected with saline (1 ml/kg). Animals were randomly divided into four groups (n=6). 1st being control group, 2nd being mCPP injected group, 3rd being mesulergine injected group and 4th group being injected with both mesulergine and mCPP. Behavioural activities of rats were monitored after 30 minutes of injection. For assessment of memory functions, water maze apparatus was used. RESULTS: Administration of mCPP impaired STM, LTM and LA of rats. Mesulergine injected rats exhibited no alteration in memory functions. However, when it was injected with mCPP then there were no memory deficits induced by mCPP. CONCLUSION: Ability of 5-HT2C receptor antagonist mesulergine to block the memory impairment effect of mCPP indicated an important regulatory role of 5-HT2C receptors in cognitive processes. PMID- 22313642 TI - Frequency of Janus associated kinase 2 (V617F) mutation in patients of polycythemia vera. AB - OBJECTIVE: To determine the frequency of Janus associated kinase 2 ( JAK2) mutation in patients of polycythemia vera (PV). STUDY DESIGN: Descriptive cross sectional. PLACE AND DURATION OF STUDY: Haematology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from January 2008 to December 2009. METHODOLOGY: Forty-six consecutive patients of PV diagnosed by the conventional haematological criteria were included in the study. Blood samples of all patients were screened for G-T point mutation (V617F) in the JAK2 gene on chromosome 9 by an allele specific polymerase chain reaction (PCR). RESULTS: JAK2 V617F mutation was found in 43 out of 46 patients (93.5%) with PV. Among them, 30 were males (65.2%) and 16 were females (34.8%). Mean TLC in patients with PV was 16.5 +/- 9.1 x 109/L, mean haemoglobin (Hb) was 17.8 +/- 2.0 g/dl, mean platelet count was 531 +/- 261 x 109/L, mean PCV was 57.9 +/- 6.3 l/l, mean MCV was 78.8 +/- 11.0 fl and mean MCH was 24.4 +/- 4.8 pg. CONCLUSION: Peripheral blood mutation screening for JAK2 V617F can be incorporated into the initial work up of patients suspected to have polycythemia as this mutation is present in majority of such patients. PMID- 22313643 TI - FibroScore for the non-invasive assessment of liver fibrosis in chronic viral hepatitis. AB - OBJECTIVE: To evaluate the predictive value of a set of laboratory markers for the assessment of liver fibrosis in chronic viral hepatitis patients. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Baqai Medical University, Combined Military Hospital, Malir, Karachi, from November 2006 to May 2008. METHODOLOGY: Twenty laboratory parameters were measured in 100 treatment naive chronic viral hepatitis patients who also had liver biopsy performed. Descriptive statistics, areas under the ROC's curves, and multivariate logistic regression analysis identified a fibrosis panel, a set of five most useful markers, for the assessment of stages of fibrosis, stage 0 to stage 4. The fibrosis index, FibroScore, consisted of bilirubin, Gamma glutamyl transferase, Hyaluronic acid, alpha 2 macroglobulin, and platelets evaluation. RESULTS: A score of >= 0.5 predicted stages 2, 3 and 4, with a sensitivity of 82%, and specificity of 92%. A score >= 0.5 for stages 3 and 4 had a sensitivity of 85%, and specificity of 89%. At a score of > 0.80, for stages 3 and 4, the sensitivity was 70%, specificity was 97%, and PPV 87% (there was >= 85% possibility of presence of stage 3 or 4). A score of <= 0.20 predicted the absence of stages 2, 3, and 4 with a sensitivity of 91%, specificity of 86%, and NPV of 96%. Scores from 0.00 to 0.10 almost certainly ruled out the presence of stages 2-4 (NPV=98%). The areas under the ROC curve were: 0.808 for stage 2; 0.938 for stage 3; and 0.959 for stage 4. CONCLUSION: A combination of 5 markers is very useful in predicting various stages of liver fibrosis, and is helpful in the non invasive assessment of liver fibrosis in chronic viral hepatitis patients. PMID- 22313644 TI - Efficacy of intra-alveolar chlorhexidine gel in reducing frequency of alveolar osteitis in mandibular third molar surgery. AB - OBJECTIVE: To determine the efficacy of intra-alveolar administration of chlorhexidine (CHX) gel in reducing the frequency of alveolar osteitis (AO) after impacted mandibular third molar surgery. STUDY DESIGN: A randomized control trial study. PLACE AND DURATION OF STUDY: Department of Oral and Maxillofacial Surgery, Armed Forces Institute of Dentistry, Rawalpindi, Pakistan, from January to December 2007. METHODOLOGY: One hundred patients including 65 males and 35 females with the age range 18-40 years were divided in two equal groups (50 each in the CHX and the control groups). Surgical removal of impacted mandibular third molar was carried out and after surgery CHX gel was placed into the alveolus of CHX group. Patients were followed at the first, second and third postoperative days. A proforma indicating presence or absence of pain, blood clot disintegration, halitosis and AO was filled for each patient. Frequencies and percentages were calculated for qualitative data. Chi-square test was applied to compare both subgroups. RESULTS: Eighteen patients (18%) were diagnosed with AO (11 males and 7 females). Out of these 18 cases, 14 (28%) were found in control group (9 males and 5 females), while 4 cases (8%) in the CHX group (2 males and 2 females). This was statistically significant p=0.017. CONCLUSION: Single application of CHX gel was effective in reducing frequency of AO following mandibular third molar surgery. PMID- 22313645 TI - Obstetrical trauma to the genital tract following vaginal delivery. AB - OBJECTIVE: To determine the frequency, types and complications of genital tract trauma during child birth. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Department of Obstetrics and Gynaecology, Unit I, Liaquat University of Medical and Health Sciences, Jamshoro, from June 2006 to May 2010. METHODOLOGY: All women who sustained genital tract trauma during delivery at the study centre and those referred from periphery with the same condition within 40 days of delivery were enrolled in the study. Exclusion criteria were women who sustained genital tract injury with caesarean section and genital tract trauma due to accident. Studied variables included age of women, parity, place of labour, type of trauma received and its immediate complications. The data was expressed in terms of descriptive statistics. RESULTS: Out of a total 9216 cases admitted in maternity ward during the study period, 467 cases (5.06%) had sustained genital tract trauma. The most frequent obstetrical trauma seen in primiparous referral cases were vaginal tears in 16 cases (25.39%) and perineal tears in 12 cases (19.04%). Multiparous women were 196 (41.97%) and cervical tears were the most frequent obstetrical trauma in them (n=52, 26.53%). Grand multiparous women were 208 having cervical tears (44.4%) and uterine rupture in 77 cases (37.01%) each. Most frequent early morbidities were postpartum haemorrhage (n= 352, 75.37%), hypovolemic shock (n= 220, 47.10%) and infection (n=158, 33.83%). The mortality rate was 16.05%. CONCLUSION: Genital tract trauma is a common complication of vaginal birth mostly seen in grand multipara, leading to haemorrhage, shock and infection. PMID- 22313646 TI - Real time polymerase chain reaction for the detection of malarial parasite. AB - OBJECTIVE: To evaluate the sensitivity and specificity of real time polymerase chain reaction (PCR) for the detection of Malarial parasite. STUDY DESIGN: Descriptive cross-sectional study. PLACE AND DURATION OF STUDY: The Armed Forces Institute of Pathology (AFIP), Rawalpindi, from April to June 2010. METHODOLOGY: A total of 60 Leishman stained blood films with clinical suspicion of malaria were studied by light microscopy for detection of malaria parasite (MP). The samples were also subjected to real time PCR for the small subunit (SSU) rRNA gene of MP found in all the four subspecies of Plasmodium. Real time PCR was done by the Taqman probe method. One sample positive for MP was serially diluted with ABO compatible blood, and light microscopy and real time PCR were performed on all dilutions. Results of light microscopy and real time PCR were compared. Sensitivity and specificity were calculated using PCR as the gold standard. RESULTS: PCR detected MP in 33 samples with sensitivity and specificity of 100% whereas light microscopy could detect MP in 30 samples. Sensitivity and specificity of light microscopy was 90.9% and 100% respectively. In the serially diluted blood sample, MP was visible at 1/16 dilution whereas the PCR showed positive results even at 1/512 dilution. CONCLUSION: Real time PCR is more sensitive than light microscopy for the detection of malarial parasite. PMID- 22313647 TI - Adverse effects of low dose methotrexate in rheumatoid arthritis patients. AB - OBJECTIVE: To determine the frequency of adverse effects attributed to Methotrexate (MTX) toxicity and serum minimum toxic concentration with low dose MTX in Rheumatoid Arthritis (RA) patients. STUDY DESIGN: Cross-sectional observational study. PLACE AND DURATION OF STUDY: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from March 2010 to March 2011. METHODOLOGY: One hundred and forty adult patients of RA receiving low dose MTX (10 mg/week) for at least 3 months, ere included by consecutive sampling. Blood samples were collected 2 hours after the oral dose of MTX. Serum alanine transaminase and creatinine were analyzed on Hitachi and blood counts on Sysmex analyzer. Serum MTX concentration was measured on TDX analyzer. RESULTS: Out of one hundred and forty patients; 68 males (49%) and 72 females (51%), 38 developed MTX toxicity (27%), comprising of hepatotoxicity in 12 (8.6%), nephrotoxicity in 3 (2.1%), anaemia in 8 (5.7%), leucopenia in 2 (1.4%), thrombocytopenia in 3 (2.1%), pancytopenia in 2 (1.4%), gastrointestinal adverse effects in 5 (3.6%) and mucocutaneous problems in 3 (2.1%). Receiver operating characteristic curve revealed serum minimum toxic concentration of MTX at cutoff value of 0.71 MUmol/l with a sensitivity of 71% and specificity of 76%. CONCLUSION: Adverse effects of low dose MTX were found in 27% of RA patients, mainly comprising of hepatotoxicity and haematological problems. MTX toxicity can be detected by therapeutic drug monitoring of serum concentration of 0.71 MUmol/l with sensitivity of 71% and specificity of 76% in the patients on low dose MTX maintenance therapy. PMID- 22313648 TI - Male partial hypogonadotrophic hypogonadism with gynaecomastia and metabolic syndrome. AB - The causal association of childhood obesity and hypogonadotrophic hypogonadism needs to be studied to unravel the cause and effect relationship between the two conditions. The relationship of hypogonadism to the Metabolic Syndrome (MetS) remains valid even when using different definitions of MetS, and following the patients prospectively for over 10 years. This is a case of 19 years male who presented with micropenis, marked gynaecomastia and weight gain. Childhood obesity and family history of diabetes predisposed him to future MetS. Presence of micropenis reflects intrauterine hypogonadotrophic hypogonadism. Both entities exacerbated each other. PMID- 22313649 TI - Angiomyofibroblastoma of the vulva. AB - A 30-year-old female presented with unilateral labial enlargement. The clinical impression was that of a benign cyst. The microscopic features were that of angiomyofibroblastoma showing hyper and hypocellular areas containing spindle and plump stromal cells admixed with blood vessels. This tumour is benign with extremely low rate of recurrence. Surgery is the only treatment as in this case. PMID- 22313650 TI - Duodenal tuberculosis. AB - Duodenal tuberculosis is an uncommon disease. It may be either extrinsic or intrinsic or both. In the extrinsic type there can either be primary duodenal involvement or compression due to enlarged paraduodenal lymph nodes. The clinical presentation can be dyspeptic or obstructive symptoms. The dyspeptic symptoms include epigastric pain, nausea, and occasional vomiting and obstructive symptoms include bilious vomiting frequently after meals, epigastric pain, and generalized abdominal pain. This report describes a young lady presenting with gastric outlet obstruction symptoms due to tuberculous adhesion involving the proximal duodenum. PMID- 22313651 TI - Pelvic-peritoneal tuberculosis mimicking ovarian cancer. AB - Pelvic-peritoneal tuberculosis is a common extrapulmonary site in young females mimicking an advanced ovarian malignancy. We present 2 cases with the classical triad of advanced-stage ovarian carcinoma-ascites, abdominopelvic masses and elevated serum CA-125 levels. Laparoscopic examination revealed peritoneal nodules which on biopsy showed granulomatous inflammation and no malignant cells. Patients were started on anti-tuberculous therapy and on follow-up their symptoms as well as CA-125 levels normalized. Medical awareness of peritoneal tuberculosis is lacking and many young women with this disease undergo unnecessary extended surgery. Diagnostic laparoscopy combined with peritoneal biopsy seems to be a sufficient and safe method to provide a definitive diagnosis for this curable infection. If left untreated, the disease may disseminate and result in significant organ dysfunctions particularly infertility. PMID- 22313652 TI - Urorectal septum malformation sequence in a newborn with VACTERL association. AB - Urorectal septum malformation sequence (URSMS) is an extremely rare anomaly, consists of multiple system anomalies including ambiguous genitalia, absence of a perineal opening, an imperforate anus, and urological, colonic and lumbosacral defects. We describe a newborn with characteristic URSMS who also had features of congenital varus deformity of leg, polydactyly, tracheo-oesophageal fistula, cardiac defect, anal atresia and hydronephrosis in antenatal ultrasound characteristic of VACTERL association. PMID- 22313653 TI - Spontaneous bilateral tubal pregnancy. AB - With the increase in incidence of ectopic pregnancy over the decades, bilateral ectopic pregnancy is also increasing. It is usually associated with assisted reproductive techniques (ART) but in recent years few cases of spontaneous bilateral ectopic pregnancy have been reported. Gynaecologists should be aware of this and that ultrasonography has limitations in diagnosis. In cases of ectopic pregnancy where contralateral adnexa is not clearly identified on ultrasound and fertility needs to be conserved, patient should be managed by experts in well equipped centres. A case of spontaneous bilateral tubal pregnancy that remained undiagnosed till laparotomy, is described. PMID- 22313654 TI - Cutis verticis gyrata secondary to infiltrating ductal carcinoma breast. AB - Cutis verticis gyrata is a long lasting and progressive condition in which there is hypertrophy and folding of the scalp skin. It typically affects the vertex and occipital region; however, it may involve the entire scalp. Classically, it has been divided into primary and secondary forms. Primary has been sub-divided into primary essential and non-essential. Secondary forms are commonly due to systemic diseases, inflammatory dermatoses, underlying nevoid abnormalities or trauma. The association between cutis verticis gyrata and malignancy is rare. It has been described in patients of leukemia, endocrine tumours and malignant melanoma. We present a case of cutis verticis gyrata in a patient of carcinoma breast. PMID- 22313655 TI - Nephrotic syndrome: a rare cause of acute coronary syndrome in a child. AB - Patients with nephrotic syndrome are at risk of developing thrombosis in both veins and arteries. Various manifestations in different organs have been reported. Thrombi in heart seen, associated with multiorgan thrombosis have been reported on autopsy earlier, but only once in a living patient with nephrotic syndrome. Here, we report a 13 years old boy with steroid-resistant nephrotic syndrome, who developed an asymptomatic but potentially hazardous large intracardiac thrombus. The child developed nephrotic syndrome at the age of 9 years and had multiple recurrences. At the age of 13 years, he developed myocardial infarction (MI) due to embolism from a large intracardiac thrombus. Later on, he was treated with heparin and warfarin anticoagulation. PMID- 22313656 TI - The acceptance rate of local anaesthesia for elective inguinal hernia repair among the surgeons working in a teaching hospital. AB - The rates for three different types of anaesthesia used for elective inguinal hernia repairs were retrospectively searched for in the hospital records in 2005 and 2010. In 2005, only 2.1% of elective inguinal hernia repairs were done with local anaesthesia. General anaesthesia was used in 93.7%, whereas regional anaesthesia in 4.2% cases. No day-case outpatient surgery was recorded after any type of anaesthesia. In 2010, local anaesthesia rate increased to 16.2%. Regional anaesthesia rate also reached to 20.6%. Ninety percent of the patients who underwent hernia repair with local anaesthesia were discharged on the day of surgery. PMID- 22313657 TI - Bacterial spectrum and their sensitivity pattern in patients of chronic suppurative otitis media. AB - The study was conducted from March 2008 to February 2010 in Microbiology Department, Citi Lab, Rawalpindi, to determine the causative microorganisms and their antibiotic sensitivity pattern in patients with chronic suppurative otitis media. One hundred and eighty-three samples received at Citi Lab were included in the study. Pus samples were cultured aerobically. Antibiotic sensitivity testing was done with standard antibiotic discs using modified Kirby-Bauer disk diffusion method. Out of 183 patients, microbiological culture was yielded from 154 specimens (84%). There were 148 bacterial isolates (96%) and 06 fungi (4%). Pseudomonas aeruginosa (n=59, 38%) was the most common isolate followed by Staphylococcus aureus (n=34, 22%). Susceptibility pattern of Pseudomonas aeruginosa showed that 100% isolates were sensitive to Piperacillin/Tazobactam, whereas 98% isolates were sensitive to Imipenem and 76% to Ciprofloxacin. Continuous surveillance of susceptibility pattern is suggestive for effective therapy of chronic suppurative otitis media. PMID- 22313658 TI - Re: School children training for basic life support. PMID- 22313659 TI - Lead foil in the intraoral periapical radiograph as an inclusion agent: a simple method in denture identification. PMID- 22313660 TI - An unusual foreign body in esophagus: tablet with its press through package (PTP). PMID- 22313661 TI - Self-prescribed and other informal care provided by physicians: scope, correlations and implications. AB - BACKGROUND: While it is generally acknowledged that self-prescribing among physicians poses some risk, research finds such behaviour to be common and in certain cases accepted by the medical community. Largely absent from the literature is knowledge about other activities doctors perform for their own medical care or for the informal treatment of family and friends. This study examined the variety, frequency and association of behaviours doctors report providing informally. Informal care included prescriptions, as well as any other type of personal medical treatment (eg, monitoring chronic or serious conditions). METHOD: A survey was sent to 2500 randomly-selected physicians in Colorado, 600 individuals returned questionnaires with usable data. The authors hypothesised: (1) physicians would prescribe the same types of treatment at home as they prescribed professionally; and (2) physicians who informally prescribed addictive medications would be more likely to engage in other types of informal medical care. RESULTS: Physicians who wrote prescriptions for antibiotics, psychotropics and opioids at work were more likely to prescribe these medications at home. Those prescribing addictive drugs outside of the office treated more serious illnesses in emergency situations, more chronic conditions and more major medical/surgical conditions informally than did those not routinely prescribing addictive medications. Physicians reported a variety of informal care behaviour and high frequency of informal care to family and friends. DISCUSSION: The frequency and variety of informal care reported in this study strongly argues for profession-wide discussion about ethical and guideline considerations for such behaviour. These areas are discussed in the paper. PMID- 22313662 TI - Palliative care registers: infringement on human rights? AB - A personal view made in light of the recent news article regarding a husband wanting to sue Addenbrooke's hospital over a Do Not Attempt Resuscitation decision. This article aims to highlight how the rolling out of cross boundary palliative care registers may be more at risk of infringing human rights. PMID- 22313663 TI - HIV-positive status and preservation of privacy: a recent decision from the Italian Data Protection Authority on the procedure of gathering personal patient data in the dental office. AB - The processing of sensitive information in the health field is subject to rigorous standards that guarantee the protection of information confidentiality. Recently, the Italian Data Protection Authority (Garante per la Protezione dei Dati Personali) stated their formal opinion on a standard procedure in dental offices involving the submission of a questionnaire that includes the patient's health status. HIV infection status is included on the form. The Authority has stated that all health data collection must be in accordance with the current Italian normative framework for personal data protection and respect the patient's freedom. This freedom allows the patient to decide, in a conscious and responsible way, whether to share health information with health personnel without experiencing any prejudice in the provision of healthcare requested. Moreover, data collection must be relevant and cannot exceed the principles of treatment goals with reference to the specific care of the concerned person. However, the need for recording information regarding HIV infection at the first appointment, regardless of the clinical intervention or therapeutic plan that needs to be conducted, should not alter the standard protection measures of the healthcare staff. In fact, these measures are adopted for every patient. PMID- 22313664 TI - The quality of informed consent: mapping the landscape. A review of empirical data from developing and developed countries. AB - OBJECTIVE: Some researchers claim that the quality of informed consent of clinical research participants in developing countries is worse than in developed countries. To evaluate this assumption, we reviewed the available data on the quality of consent in both settings. METHODS: We conducted a comprehensive PubMed search, examined bibliographies and literature reviews, and consulted with international experts on informed consent in order to identify studies published from 1966 to 2010 that used quantitative methods, surveyed participants or parents of paediatric participants in actual trials, assessed comprehension and/or voluntariness, and did not involve testing particular consent interventions. Forty-seven studies met these criteria. We compared data about participant comprehension and voluntariness. The paucity of data and variation in study methodology limit comparison and preclude statistical aggregation of the data. RESULTS AND DISCUSSION: This review shows that the assertion that informed consent is worse in developing countries than in developed countries is a simplification of a complex picture. Despite the limitations of comparison, the data suggest that: (1) comprehension of study information varies among participants in both developed and developing countries, and comprehension of randomisation and placebo controlled designs is poorer than comprehension of other aspects of trials in both settings; and (2) participants in developing countries appear to be less likely than those in developed countries to say they can refuse participation in or withdraw from a trial, and are more likely to worry about the consequences of refusal or withdrawal. PMID- 22313666 TI - Impact when receiving a diagnosis: additive and multiplicative effects between illness severity and perception of control. AB - Based on Lazarus' transactional model of stress, this study examined how the information provided in a medical diagnosis (the severity of the illness, the effectiveness of the treatment and the self-efficacy to follow this treatment) are combined to generate perception of stress. Twenty-seven scenarios were presented to 152 volunteer students and their level of perceived stress was recorded. Results revealed that the lack of efficacy of the treatment raises the perception of stress proportionally to the different degrees of illness severity, but having a low perceived ability to follow the treatment triggers high levels of stress, particularly when the diagnosis is serious. PMID- 22313665 TI - Effects of a high-fat diet and bamboo extract supplement on anxiety- and depression-like neurobehaviours in mice. AB - High-fat diet is a major causative factor of overweight and obesity, which are associated with an increased risk of neuropsychiatric diseases, such as anxiety and depression. In the present study, we investigated the protective effects of bamboo extract (BEX) on anxiety- and depression-like neurobehaviours in mice treated with a high-fat diet. Male mice with CD-1 genetic background were treated for 2 months with either a standard or a high-fat diet (10 or 45 % energy from fat, respectively), with or without the BEX supplement (11 g dry mass per 17 MJ). The anxiety levels of mice were evaluated using open-field and hole-board tests, and depression was measured using the force-swimming test. The anxiety responses of the animals were found significantly increased after the high-fat diet treatment, and this elevation was effectively abolished by the BEX supplement. The high-fat diet seemed to have an anti-depressive effect in mice at the tested time point, but the effect of the BEX supplement on the depression level of the animals was not conclusive. The high-fat diet significantly decreased total glutathione content in the blood while the BEX supplement increased glutathione oxidation. In summary, the present study shows that decreased total glutathione concentration in the blood co-occurred with a high-fat treatment, high anxiety level and low depression level in mice, and when supplemented in a high-fat diet, BEX had an anxiolytic effect in mice. PMID- 22313667 TI - Healthy, wealthy, wise? Psychosocial factors influencing the socioeconomic status health gradient. AB - The present research investigated psychosocial factors: control beliefs; social relations moderating the SES-health gradient. Participants included 3775 respondents from a national probability sample, Midlife in United States (t(1): Age, M = 46.40, SD = 13.00, t(2): Age, M = 55.47, SD = 12.43), who provided reports on control beliefs, social relations, and health at two assessment occasions (1994/1995 and 2002/2003). Hierarchical regression demonstrated that control beliefs, social support, and strain uniquely moderated relationships between SES and longitudinal health. The present study highlights the importance of psychosocial factors as protective mechanisms of socioeconomic disadvantages and associated long-term deleterious health outcomes. PMID- 22313668 TI - Racial discrimination and health-promoting vs damaging behaviors among African American adults. AB - Studies have found relationships between racial discrimination and increased health-damaging behaviors among African-Americans, but have not examined possible concomitant decreased health-promoting behaviors. We explored the role of discrimination in two health-promoting behaviors, consuming >= 5 fruits/vegetables daily (FVC) and physical activity (PA), for the first time, and likewise examined discrimination's contribution to cigarette smoking, among a sample of N = 2118 African-American adults. Results revealed that discrimination contributed positively to smoking and to PA but was unrelated to FVC. These findings suggest that both adaptive and maladaptive health behaviors might be used to cope with the stress of discrimination. PMID- 22313669 TI - The impact of perceived stress and perceived control on anxiety and mood disorders in noncardiac chest pain. AB - Chest pain without detectable heart disease, noncardiac chest pain (NCCP), is linked with anxiety and depression. Theory posits stress and perceived control may relate to NCCP. We hypothesized stress would have direct and mediated effects via perceived control on anxiety and mood disorders in NCCP. Patients (N = 113) completed questionnaires and a structured diagnostic interview. Stress and perceived control were associated with anxiety and mood disorder severity. Perceived control fully mediated the relation between stress and mood disorder severity but not anxiety disorder severity. Results are partially supportive of anxiety-based theories of NCCP. PMID- 22313670 TI - Passion in breast cancer survivors: examining links to emotional well-being. AB - This study (1) identified the activities that breast cancer survivors report as passionate; (2) examined whether levels of passion differed based on the types of passionate activities reported and; (3) examined the association between harmonious and obsessive passion and emotional well-being. Early post-treatment breast cancer survivors (N = 177) reported passionate physical activities as most prevalent, and reported higher harmonious passion scores compared to women reporting relaxing and social leisure activities. Harmonious passion was associated with higher positive affect and lower cancer worry. Obsessive passion was linked to higher negative affect, cancer worry, and posttraumatic growth. Passion is important for enhanced well-being. PMID- 22313671 TI - Family functioning and binge drinking among Italian adolescents. AB - Limited studies have sought to describe binge drinking among adolescents and even fewer studies have attempted to examine whether family functioning, family communication and satisfaction could be associated with alcohol abuse. Our sample was made up of 726 Italian adolescents between the ages of 16 and 18. According to previous research, adolescents were categorized into non-drinkers, social, binge and heavy drinkers. Results showed that social, binge and heavy drinkers differ in terms of some drinking variables, family functioning, family communication and satisfaction. PMID- 22313672 TI - Debiasing comparative optimism and increasing worry for health outcomes. AB - Comparative optimism - feeling at less personal risk for negative outcomes than one's peers - has been linked to reduced prevention efforts. This study examined a novel debiasing technique aimed at simultaneously reducing both indirectly and directly measured comparative optimism. Before providing direct comparative estimates, participants provided absolute self and peer estimates in a joint format (same computer screen) or a separate format (different computer screens). Relative to the separate format condition, participants in the joint format condition showed (1) lower comparative optimism in absolute/indirect measures, (2) lower direct comparative optimism, and (3) heightened worry. Implications for risk perception screening are discussed. PMID- 22313673 TI - Invasion from a cell aggregate--the roles of active cell motion and mechanical equilibrium. AB - Cell invasion from an aggregate into a surrounding extracellular matrix (ECM) is an important process during development disease, e.g., vascular network assembly or tumor progression. To describe the behavior emerging from autonomous cell motility, cell-cell adhesion and contact guidance by ECM filaments, we propose a suitably modified cellular Potts model. We consider an active cell motility process in which internal polarity is governed by a positive feedback from cell displacements, a mechanism that can result in highly persistent motion when constrained by an oriented ECM structure. The model allows us to explore the interplay between haptotaxis, matrix degradation and active cell movement. We show that for certain conditions the cells are able to both invade the ECM and follow the ECM tracks. Furthermore, we argue that enforcing mechanical equilibrium within a bulk cell mass is of key importance in multicellular simulations. PMID- 22313675 TI - Rapid detection of urinary tract pathogens using microcalorimetry: principle, technique and first results. AB - What's known on the subject? and What does the study add? Microcalorimetry has been applied in several microbiological studies, but never in a clinical urological context. In addition, basic knowledge on the growth of urinary pathogens in urine is still scarce and data regarding the growth rate of many urinary pathogens in urine are still not available. The study demonstrates that this innovative application of microcalorimetry is useful in (i) investigating the growth of urinary pathogens in sterilized urine and (ii) as a rapid tool for diagnosis of urinary infection as well as for further identification of the causative infectious agent. OBJECTIVE: To investigate the value of isothermal microcalorimetry (IMC) in the detection and differentiation of common urinary tract pathogens in urine. IMC is a non-specific analytical tool for the measurement of heat in the microwatt range. PATIENTS AND METHODS: A microcalorimeter equipped with 48 channels was used. Detection was accomplished, and growth was monitored for four bacterial strains in sterilized urine at 37 degrees C by measuring metabolic heat flow (uW = uJ/s) as a function of time. The strains were Escherichia coli, Proteus mirabilis, Enterococcus faecalis and Staphylococcus aureus. RESULTS: Bacterial growth was detected after 3.1 to 17.1 h with decreasing inocula. The detection limit was 1 colony-forming unit (CFU)/mL for E. coli, 10 CFU/mL for P. mirabilis and E. faecalis and 10(3) CFU/mL for S. aureus. The total heat was highest in P. mirabilis ranging from 10 to 12 J, followed by E. coli (3-4 J), S. aureus (2-3 J) and E. faecalis (1.3-1.5 J). The shape of the heat flow curves was characteristic for each species independent of its initial concentration. CONCLUSIONS: IMC allows rapid detection of bacteriuria, much faster than conventional culture. Urinary tract pathogen detection after only 3.1 h is realistic. Clearly different heat flow patterns enable accurate pathogen differentiation. Due to expeditious identification of urine samples that contain only low colony counts (i.e. less than 10(3) CFU/mL), IMC may become a valuable screening tool for detecting the presence of significant bacteriuria. PMID- 22313674 TI - Strain dependent gene expression and neurochemical levels in the brain of zebrafish: focus on a few alcohol related targets. AB - The zebrafish is becoming increasingly popular in behavior genetics because it may allow one to conduct large scale mutation and drug screens facilitating the discovery of mechanisms of complex traits. Strain differences in adult zebrafish behavior have already been reported, which may have important implications in neurobehavioral genetics. For example, we have found the AB and SF strains to differ in their behavioral responses to both acute and chronic alcohol exposure. In the current study, we further characterize these strains using semi quantitative RT-PCR to measure the expression of ten selected genes and HPLC to measure the levels of nine neurochemicals. We chose the target genes and neurochemicals based upon their potential involvement in alcohol and other drugs of abuse related mechanisms. We quantified the expression of the genes encoding D1-R, D2a-R, D4a-R dopamine receptors, GABA(A)-R, GABA(B)-R1, GAD1, MAO, NMDA-R (NR2D subunit), 5HT-R1bd and SLC6 a4a. We found the gene encoding D1 dopamine receptor over-expressed and the genes encoding GABA(B1) receptor and solute family carrier protein 6 (SLC6) 4a under-expressed in SF compared to AB. We also found the level of all (dopamine, DOPAC, Serotonin, GABA, Glutamate, Glycine, Aspartate, Taurine) but one (5HIAA) neurochemicals tested decreased in SF as compared to AB. These results, combined with previously identified behavioral differences between the AB and SF strains, demonstrate the importance of strain characterization in zebrafish. They now also allow formulation of working hypotheses about possible mechanisms underlying the differential effects of acute and chronic alcohol treatment on these two zebrafish strains. PMID- 22313676 TI - Continuous presence of H2O2 induces mitochondrial-mediated, MAPK- and caspase independent growth inhibition and cytotoxicity in human gingival fibroblasts. AB - The continuous generation of reactive oxygen species (ROS) is one of the most important events that occur during periodontal inflammation. Hydrogen peroxide (H(2)O(2)) is widely used in dental clinics. Many investigators have tried to elucidate the exact effect of H(2)O(2) on human gingival fibroblasts (HGFs). These studies have shown that H(2)O(2) induces growth inhibition and apoptosis in cells. However, the mechanisms involved in H(2)O(2)-induced cell death in HGFs are not completely understood. In this study, we examine how continuously generated H(2)O(2) affects the viability and proliferation of HGFs using glucose oxidase (GO). We also explored the mechanisms by which the continuous presence of H(2)O(2) induces cell death. GO treatment not only inhibited HGF growth and proliferation, but it also induced cell death in HGFs without typical apoptotic features such as nuclear DNA laddering. This GO-mediated cytotoxicity was proportional to the levels of intracellular ROS that were generated, rather than proportional to changes of cellular antioxidant activities. GO treatment also resulted in the loss of mitochondrial membrane potential and the relocation of mitochondrial apoptogenic factors. There was also an acute and severe depletion of cellular ATP levels. However, none of the pharmacological inhibitors specific for mitogen-activated protein kinases (MAPKs) or pancaspase prevented GO-induced cell death. Treatment with either catalase or acteoside significantly attenuated the GO-mediated cytotoxicity in the HGFs, thereby suggesting a protective effect of antioxidants against ROS-mediated gingival damage. Here we demonstrate that continuously generated H(2)O(2) not only inhibits the viability and proliferation of HGFs, but also causes pyknotic/necrotic cell death through mitochondrial stress-mediated, MAPK- and caspase-independent pathways. PMID- 22313677 TI - Motorcycle exhaust particles up-regulate expression of vascular adhesion molecule 1 and intercellular adhesion molecule-1 in human umbilical vein endothelial cells. AB - Epidemiological studies have shown that there is a strong correlation between atherosclerosis and ambient air pollution. In this study, we found that motorcycle exhaust particles (MEP) induced adhesion between cells of the human monocytic leukemia cell line (THP-1) and human umbilical vein endothelial cells (HUVECs) in a time-and dose-dependent manner. In addition, MEP treatment induced both mRNA and protein expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HUVECs. The IkappaB degradation and p65 nuclear translocation was found in MEP-treated HUVECs, suggested the involvement of nuclear factor-kappaB (NF-kappaB). MEP-induced VCAM-1 and ICAM-1 protein expression was inhibited by NF-kappaB inhibitor BAY 11-7085. Oxidative stress was also involved in the signaling of VCAM-1 and ICAM-1 expression. MEP treatment caused hydrogen peroxide and superoxide formation. Pretreatment with alpha-tocopherol could inhibit MEP-induced reactive oxygen intermediates generation and suppressed MEP-induced IkappaB degradation and adhesion molecules expression. Furthermore, the carbon black (CB) nanoparticles with different diameters could induce VCAM-1 and ICAM-1 protein expression; however, polycyclic aromatic hydrocarbons (PAHs) only increased the expression of ICAM-1 but not that of VCAM-1 in HUVECs. In this study, we found that MEPs could induce ICAM-1 and VCAM-1 expression through oxidative stress and NF-kappaB activation in HUVECs. PMID- 22313678 TI - Predicting tissue specific cis-regulatory modules in the human genome using pairs of co-occurring motifs. AB - BACKGROUND: Researchers seeking to unlock the genetic basis of human physiology and diseases have been studying gene transcription regulation. The temporal and spatial patterns of gene expression are controlled by mainly non-coding elements known as cis-regulatory modules (CRMs) and epigenetic factors. CRMs modulating related genes share the regulatory signature which consists of transcription factor (TF) binding sites (TFBSs). Identifying such CRMs is a challenging problem due to the prohibitive number of sequence sets that need to be analyzed. RESULTS: We formulated the challenge as a supervised classification problem even though experimentally validated CRMs were not required. Our efforts resulted in a software system named CrmMiner. The system mines for CRMs in the vicinity of related genes. CrmMiner requires two sets of sequences: a mixed set and a control set. Sequences in the vicinity of the related genes comprise the mixed set, whereas the control set includes random genomic sequences. CrmMiner assumes that a large percentage of the mixed set is made of background sequences that do not include CRMs. The system identifies pairs of closely located motifs representing vertebrate TFBSs that are enriched in the training mixed set consisting of 50% of the gene loci. In addition, CrmMiner selects a group of the enriched pairs to represent the tissue-specific regulatory signature. The mixed and the control sets are searched for candidate sequences that include any of the selected pairs. Next, an optimal Bayesian classifier is used to distinguish candidates found in the mixed set from their control counterparts. Our study proposes 62 tissue specific regulatory signatures and putative CRMs for different human tissues and cell types. These signatures consist of assortments of ubiquitously expressed TFs and tissue-specific TFs. Under controlled settings, CrmMiner identified known CRMs in noisy sets up to 1:25 signal-to-noise ratio. CrmMiner was 21-75% more precise than a related CRM predictor. The sensitivity of the system to locate known human heart enhancers reached up to 83%. CrmMiner precision reached 82% while mining for CRMs specific to the human CD4+ T cells. On several data sets, the system achieved 99% specificity. CONCLUSION: These results suggest that CrmMiner predictions are accurate and likely to be tissue-specific CRMs. We expect that the predicted tissue-specific CRMs and the regulatory signatures broaden our knowledge of gene transcription regulation. PMID- 22313679 TI - Heterogeneity of the state and functionality of water molecules sorbed in an amorphous sugar matrix. AB - An amorphous matrix, comprised of sugar molecules, is frequently used in the pharmaceutical industry. An amorphous sugar matrix exhibits high hygroscopicity, and it has been established that the sorbed water lowers the glass transition temperature T(g) of the amorphous sugar matrix. It is naturally expected that the random allocation and configuration of sugar molecules would result in heterogeneity of states for sorbed water. However, most analyses of the behavior of water, when sorbed to an amorphous sugar matrix, have implicitly assumed that all of the sorbed water molecules are in a single state. In this study, the states of water molecules sorbed in an amorphous sugar matrix were analyzed by Fourier-transform IR spectroscopy and a Fourier self-deconvolution technique. When sorbed water molecules were classified into five states, according to the extent to which they are restricted, three of the states resulted in a lowering of T(g) of an amorphous sugar matrix, while the other two were independent of the plasticization of the matrix. This finding provides an explanation for the paradoxical fact that compression at several hundreds of MPa significantly decreases the equilibrium water content at a given RH, while the T(g) remains unchanged. PMID- 22313680 TI - 4D cardiovascular magnetic resonance velocity mapping of alterations of right heart flow patterns and main pulmonary artery hemodynamics in tetralogy of Fallot. AB - BACKGROUND: To assess changes in right heart flow and pulmonary artery hemodynamics in patients with repaired Tetralogy of Fallot (rTOF) we used whole heart, four dimensional (4D) velocity mapping (VM) cardiovascular magnetic resonance (CMR). METHODS: CMR studies were performed in 11 subjects with rTOF (5M/6F; 20.1 +/- 12.4 years) and 10 normal volunteers (6M/4F; 34.2 +/- 13.4 years) on clinical 1.5T and 3.0T MR scanners. 4D VM-CMR was performed using PC VIPR (Phase Contrast Vastly undersampled Isotropic Projection Reconstruction). Interactive streamline and particle trace visualizations of the superior and inferior vena cava (IVC and SVC, respectively), right atrium (RA), right ventricle (RV), and pulmonary artery (PA) were generated and reviewed by three experienced readers. Main PA net flow, retrograde flow, peak flow, time-to-peak flow, peak acceleration, resistance index and mean wall shear stress were quantified. Differences in flow patterns between the two groups were tested using Fisher's exact test. Differences in quantitative parameters were analyzed with the Kruskal-Wallis rank sum test. RESULTS: 4D VM-CMR was successfully performed in all volunteers and subjects with TOF. Right heart flow patterns in rTOF subjects were characterized by (a) greater SVC/IVC flow during diastole than systole, (b) increased vortical flow patterns in the RA and in the RV during diastole, and (c) increased helical or vortical flow features in the PA's. Differences in main PA retrograde flow, resistance index, peak flow, time-to-peak flow, peak acceleration and mean wall shear stress were statistically significant. CONCLUSIONS: Whole heart 4D VM-CMR with PC VIPR enables detection of both normal and abnormal right heart flow patterns, which may allow for comprehensive studies to evaluate interdependencies of post-surgically altered geometries and hemodynamics. PMID- 22313681 TI - MRSA-ST398 in livestock farmers and neighbouring residents in a rural area in Germany. AB - Prevalence of and risk factors associated with MRSA-ST398 carriage in 1872 (response 70%) farmers and neighbouring residents in a pig- and poultry-dense area in Germany were investigated using a cross-sectional study and self-sampling nasal swabs. In the population, 1% without occupational livestock contact and 24% with occupational livestock contact tested positive for MRSA-ST398. The group without occupational livestock contact was 3.8 times [95% confidence interval (CI) 1.5-9.3] more likely to be colonized if a household member had livestock contact and 3.2 times (95% CI 1.4-7.4) more likely if they regularly made private farm visits (e.g. to buy eggs or milk). In the group with occupational livestock contact, pig contact had an odds ratio of 7.1 (95% CI 2.9-17.2) for MRSA-ST398 acquisition. This is the first study to associate private farm visits with acquisition of MRSA; more research to explore the exact transmission routes is necessary. PMID- 22313682 TI - Overexpression of DNA damage-induced 45 alpha gene contributes to esophageal squamous cell cancer by promoter hypomethylation. AB - BACKGROUND: Environmental factors-induced dysfunction of esophageal squamous epithelium, including genomic DNA impairment and apoptosis, play an important role in the pathogenesis of esophageal squamous cell cancer. DNA damage-induced 45alpha (GADD45alpha) has been found promoting DNA repair and removing methylation marker, Therefore, in this study we will investigate whether GADD45alpha expression is induced and its mechanism in esophageal squamous cell cancer. METHODS: Two human esophageal squamous cell lines (ESCC), ECA109 and KYSE510 were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS). Lipofectamine 2000 was used to transfect cells. mRNA level of GADD45alpha was measured by reverse transcription-quantitive PCR (RT-qPCR), protein level of GADD45alpha was detected by western blot and Immunohistochemistry. Global DNA methylation of tissue sample was measured using the Methylamp Global DNA Methylation Quantification Ultra kit (Epigentek Group) and promoter methylation was measured by bisulfite sequencing. RESULTS: GADD45a mRNA and protein levels were increased significantly in tumor tissue than that in adjacent normal tissue. Hypomethylation of global genomic DNA and GADD45alpha promoter were found in ESCC. The cell sensitivity to Cisplatin DDP was decreased significantly in Eca109 and Kyse510 cells, in which GADD45alpha expression was down-regulated by RNA interference (RNAi). In addition, silence of GADD45a expression in ESCC cells inhibited proliferation and promoted apoptosis. CONCLUSION: Overexpression of GADD45alpha gene is due to DNA hypomethylation in ESCC. GADD45alpha may be a protective factor in DDP chemotherapy for esophageal squamous cell carcinoma. PMID- 22313683 TI - Lactic acid bacteria isolated from rye sourdoughs produce bacteriocin-like inhibitory substances active against Bacillus subtilis and fungi. AB - AIM: To screen five strains of lactic acid bacteria (LAB) isolated from rye sourdoughs for the potential production of antimicrobial substances. METHODS AND RESULTS: Lactobacillus sakei KTU05-06, Pediococcus acidilactici KTU05-7, Pediococcus pentosaceus KTU05-8, KTU05-9 and KTU05-10 isolated from rye sourdoughs were investigated for the production of bacteriocin-like inhibitory substances (BLIS). The supernatants of analysed LAB inhibited growth of up to 15 out of 25 indicator bacteria strains as well as up to 25 out of 56 LAB strains isolated from rye sourdoughs. Moreover, these five LAB were active against ropes producing Bacillus subtilis and the main bread mould spoilage causing fungi Aspergillus, Fusarium, Mucor and Penicillium. Lactobacillus sakei KTU05-6 demonstrated the best antibacterial properties and is resistant towards heat treatment even at 100 degrees C for 60 min. CONCLUSIONS: The use of LAB-producing antibacterial substances may be a good choice as a co-starter culture to ensure the stability of sourdoughs and to avoid the bacterial and fungi spoilage of the end product. SIGNIFICANCE AND IMPACT OF THE STUDY: The antimicrobial compounds designated as sakacin KTU05-6, pediocin KTU05-8 KTU05-9, KTU05-10 and AcKTU05-67 were not identical to any other known BLIS, and this finding leads up to the assumption that they might be the novel. PMID- 22313684 TI - Effect of purified beta-glucans derived from Laminaria digitata, Laminaria hyperborea and Saccharomyces cerevisiae on piglet performance, selected bacterial populations, volatile fatty acids and pro-inflammatory cytokines in the gastrointestinal tract of pigs. AB - beta-Glucans have been identified as natural biomolecules with immunomodulatory activity. The first objective of the present study was to compare the effects of purified beta-glucans derived from Laminaria digitata, L. hyperborea and Saccharomyces cerevisiae on piglet performance, selected bacterial populations and intestinal volatile fatty acid (VFA) production. The second aim was to compare the gene expression profiles of the markers of pro- and anti-inflammation in both unchallenged and lipopolysaccharide (LPS)-challenged ileal and colonic tissues. beta-Glucans were included at 250 mg/kg in the diets. The beta-glucans derived from L. hyperborea, L. digitata and S. cerevisiae all reduced the Enterobacteriaceae population (P<0.05) without influencing the lactobacilli and bifidobacteria populations (P>0.05) in the ileum and colon. There was a significant interaction between gastrointestinal region and beta-glucan source in the expression of cytokine markers, IL-1alpha (<0.001), IL-10 (P<0.05), TNF-alpha (P<0.05) and IL-17A (P<0.001). beta-Glucans did not stimulate any pro- or anti inflammatory cytokine markers in the ileal epithelial cells. In contrast, the expression of a panel of pro- and anti-inflammatory cytokines (IL-1alpha, IL-10, TNF-alpha and IL-17A) was down-regulated in the colon following exposure to beta glucans from all the three sources. However, the data suggest that the soluble beta-glucans derived from L. digitata may be acting via a different mechanism from the insoluble beta-glucans derived from L. hyperborea and S. cerevisiae, as the VFA profile was different in the L. digitata-treated animals. There was an increase in IL-8 gene expression (P<0.05) in the gastrointestinal tract from the animals exposed to L. digitata following an LPS ex vivo challenge that was not evident in the other two treatment groups. In conclusion, beta-glucans from both seaweed and yeast sources reduce Enterobacteriaceae counts and pro-inflammatory markers in the colon, though the mechanisms of action may be different between the soluble and insoluble fibre sources. PMID- 22313685 TI - Histone deacetylase inhibitor-mediated sensitization to TRAIL-induced apoptosis in childhood malignancies is not associated with upregulation of TRAIL receptor expression, but with potentiated caspase-8 activation. AB - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has great potential for the treatment of cancer because it targets tumor cells while sparing normal cells. Several cancers, however, fail to respond to TRAIL's antineoplastic effects. These resistant tumors require cotreatment with sensitizing agents in order for TRAIL to exert anticancer activity. Histone deacetylase inhibitors (HDACi) have been recognized as potent TRAIL sensitizers. In searching for the determinants of TRAIL responsiveness, HDACi-mediated TRAIL sensitization has been predominantly attributed to TRAIL receptor upregulation. This explanation, however, has been challenged by a few studies. The aim of the present study was to explore the relevance of TRAIL receptor expression for HDACi mediated TRAIL sensitization in childhood tumors, i.e., in medulloblastoma, Ewing's sarcoma and osteosarcoma. In previous studies, we had shown that TRAIL and HDACi were synergistic in inducing apoptosis in medulloblastoma and Ewing's sarcoma. In the present study, we demonstrate that HDACi cooperated with TRAIL in eliciting cell death in osteosarcoma. However, HDACi treatment did not alter or even reduced cell surface expression of TRAIL receptors in the three childhood tumors. In gaining insight into the apoptotic pathway involved in TRAIL sensitization, HDACi were found to potentiate TRAIL-induced caspase-8 activation. Taken together, our findings suggest that HDACi-mediated TRAIL sensitization is not the result of TRAIL receptor upregulation, but the result of a receptor proximal event in childhood tumor cells. PMID- 22313686 TI - Gefitinib (ZD1839) increases the efficacy of cisplatin in ovarian cancer cells. AB - We examined the effect of gefitinib (ZD1839), a selective epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, on cytotoxicity to cisplatin, EGFR downstream signaling, apoptosis and the association between the inhibition of DNA repair by gefitinib and the expression of DNA-dependent protein kinase (DNA-PK) using three ovarian cancer cell lines. In the presence of gefitinib, cisplatin induced growth inhibition and apoptosis were significantly enhanced in Caov-3 and RMG-1 cells, which express EGFR, and in A2780, which lacks EGFR but expresses HER 2. Gefitinib significantly inhibited the cisplatin-induced ERK and Akt activation in Caov-3 and RMG-1 cells but not in A2780 cells. In all three cell lines, there was delayed repair of DNA intrastrand cross-links damaged by cisplatin used in combination with gefitinib, compared with cisplatin alone. The reduction in DNA PK levels persisted when cells were exposed to combinations of cisplatin and gefitinib in all cell lines. Moreover, the delayed repair was cancelled by anti HER2 small-interfering RNA transfection in A2780 cells. These results suggest that combination therapy with cisplatin and gefitinib may increase the therapeutic efficacy of cisplatin by blocking EGFR downstream signaling and/or inhibiting DNA repair in ovarian cancer. PMID- 22313688 TI - The use of triclosan eluting stents effectively reduces ureteral stent symptoms: a prospective randomized trial. AB - What's known on the subject? and What does the study add? Infection, encrustation and ureteral-stent-related symptoms (USRS) including pain, urgency and frequency are all major problems associated with stent use. No current ureteral stent or exogenously applied therapy adequately deals with these problems and antibiotic use is ineffective once a bacterial biofilm forms on the device. Triclosan is a broad spectrum antibacterial agent widely used in numerous healthcare products and has been previously shown to reduce inflammation on the skin and in the oral cavity. This study tested a triclosan-impregnated ureteral stent for its ability to reduce infection, encrustation and USRS. This study shows that while a triclosan-impregnated ureteral stent cannot reduce infection rates alone compared with antibiotic use, the stent can reduce several USRS including pain during indwelling. This study suggests that the triclosan eluting stent may have a role in treating patients, perhaps in combination with standard antibiotic therapy. OBJECTIVE: To evaluate the capacity of triclosan-loaded ureteral stents to reduce stent-associated bacterial attachment, biofilm formation and encrustation, thereby potentially reducing infection development and other device-related sequelae. PATIENTS AND METHODS: Twenty subjects requiring short-term stenting (7 15 days) were randomized to receive either a Percuflex Plus((r)) non-eluting stent (control) or a Triumph((r)) triclosan eluting stent. Control-stented subjects received 3 days of levofloxacin prophylaxis (500 mg once daily) while Triumph((r))-stented subjects did not. All subjects were assessed for positive urine and stent cultures, stent biofilm development and encrustation. Following device removal, each subject completed an analogue-scale symptom assessment questionnaire. RESULTS: Ureteral stenting was performed after nine ureteroscopic and one extracorporeal shock wave lithotripsy procedure in the control group and eight ureteroscopic and two shock wave lithotripsy procedures in the triclosan group. No significant differences were observed for culture, biofilm and encrustation between the two groups. Subjects in the triclosan group reported significant reductions in lower flank pain scores during activity (58.1% reduction, P = 0.017) and urination (42.6%, P = 0.041), abdominal pain during activity (42.1%, P = 0.042) and urethral pain during urination (31.7%, P = 0.049). CONCLUSIONS: In this study, the use of the Triumph((r)) triclosan eluting stent had no marked impact on biofilm formation, encrustation or infection development in short-term stented patients. The Triumph((r)) device led to significant reductions in several common ureteral-stent-related symptoms, supporting its use in this patient population. PMID- 22313687 TI - Enhancing CHK1 inhibitor lethality in glioblastoma. AB - The present studies were initiated to determine whether inhibitors of MEK1/2 or SRC signaling, respectively, enhance CHK1 inhibitor lethality in primary human glioblastoma cells. Multiple MEK1/2 inhibitors (CI-1040 (PD184352); AZD6244 (ARRY 142886)) interacted with multiple CHK1 inhibitors (UCN-01, AZD7762) to kill multiple primary human glioma cell isolates that have a diverse set of genetic alterations typically found in the disease. Inhibition of SRC family proteins also enhanced CHK1 inhibitor lethality. Combined treatment of glioma cells with (MEK1/2 + CHK1) inhibitors enhanced radiosensitivity. Combined (MEK1/2 + CHK1) inhibitor treatment led to dephosphorylation of ERK1/2 and S6 ribosomal protein, whereas the phosphorylation of JNK and p38 was increased. MEK1/2 + CHK1 inhibitor stimulated cell death was associated with the cleavage of pro-caspases 3 and 7 as well as the caspase substrate (PARP). We also observed activation of pro apoptotic BCL-2 effector proteins BAK and BAX and reduced levels of pro-survival BCL-2 family protein BCL-XL. Overexpression of BCL-XL alleviated but did not completely abolish MEK1/2 + CHK1 inhibitor cytotoxicity in GBM cells. These findings argue that multiple inhibitors of the SRC-MEK pathway have the potential to interact with multiple CHK1 inhibitors to kill glioma cells. PMID- 22313690 TI - Modeling the Q-cycle mechanism of transmembrane energy conversion. AB - The Q-cycle mechanism plays an important role in the conversion of the redox energy into the energy of the proton electrochemical gradient across the biomembrane. The bifurcated electron transfer reaction, which is built into this mechanism, recycles one electron, thus allowing us to translocate two protons per one electron moving to the high-potential redox chain. We study a kinetic model of the Q-cycle mechanism in an artificial system which mimics the bf complex of plants and cyanobacteria in the regime of ferredoxin-dependent cyclic electron flow. Using methods of condensed matter physics, we derive a set of master equations and describe a time sequence of electron and proton transfer reactions in the complex. We find energetic conditions when the bifurcation of the electron pathways at the positive side of the membrane occurs naturally, without any additional gates. For reasonable parameter values, we show that this system is able to translocate more than 1.8 protons, on average, per one electron, with a thermodynamic efficiency of the order of 32% or higher. PMID- 22313691 TI - IKK-beta mediates chemoresistance by sequestering FOXO3; a critical factor for cell survival and death. AB - Chemotherapeutic drugs proved only 50% successful in breast cancer because of cell type-dependent resistance mechanisms. FOXO3 is known to be involved in the regulation of several cell death-related genes; however, the extent of FOXO3 regulation in chemoresistance is still not fully understood. Here, we show that FOXO3 critically mediates cisplatin chemosensitivity of MCF-7 breast cancer cells which express higher levels of FOXO3 compared to resistant MDA-MB-231 cells. Administration of cisplatin induces apoptosis in MCF-7 cells in a FOXO3-dependent manner as indicated by RNA interference. On the other hand, IKK-beta (IkappaB kinase) appears to inhibit FOXO3 action after cisplatin treatment and promotes chemoresistance in MDA-MB-231 cells. IKK-beta directly interacts and sequesters FOXO3 in the cytosol preventing its nuclear localization. Moreover, cisplatin treatment induces autophagosome formation through LC-3 conversion while inhibiting the cleavage of caspase 9 and caspase 3 in MDA-MB-231 cells manipulated to overexpress FOXO3. In brief, our findings demonstrate that in addition to cellular level of active FOXO3, cisplatin chemoresistance is also regulated by IKK-beta sequestration of FOXO3 in cytosol. PMID- 22313689 TI - Oxidative genome damage and its repair: implications in aging and neurodegenerative diseases. AB - Reactive oxygen species (ROS), generated endogenously during respiration or exogenously by genotoxic agents, induce oxidized bases and single-strand breaks (SSBs) in DNA that are repaired via the base excision/SSB repair (BER/SSBR) pathway in both the nucleus and mitochondria. Tightly regulated BER/SSBR with multiple sub-pathways is highly complex, and is linked to the replication and transcription. The repair-initiating DNA glycosylases (DGs) or AP-endonuclease (APE1) control the sub-pathway by stably interacting with downstream proteins usually via their common interacting domain (CID). A nonconserved CID with disordered structure usually located at one of the termini includes the sequences for covalent modifications and/or organelle targeting. While the DGs are individually dispensable, the SSBR-initiating APE1 and polynucleotide kinase 3' phosphatase (PNKP) are essential. BER/SSBR of mammalian nuclear and mitochondrial genomes share the same early enzymes. Accumulation of oxidative damage in nuclear and mitochondrial genomes has been implicated in aging and various neurological disorders. While defects in BER/SSBR proteins have been linked to hereditary neurodegenerative diseases, our recent studies implicated transition metal induced inhibition of NEIL family DGs in sporadic diseases. This review focuses on the recent advances in repair of oxidatively damages in mammalian genomes and their linkage to aging and neurological disorders. PMID- 22313692 TI - Treponema denticola chymotrypsin-like proteinase (CTLP) integrates spirochaetes within oral microbial communities. AB - Treponema denticola is found ubiquitously in the human oral cavity and is mainly associated with bacterial communities implicated in the establishment and development of periodontal disease. The ability to become integrated within biofilm communities is crucial to the growth and survival of oral bacteria, and involves inter-bacterial coaggregation, metabolic cooperation, and synergy against host defences. In this article we show that the chymotrypsin-like proteinase (CTLP), found within a high-molecular-mass complex on the cell surface, mediates adherence of T. denticola to other potential periodontal pathogens, Porphyromonas gingivalis, Fusobacterium nucleatum, Prevotella intermedia and Parvimonas micra. Proteolytic activity per se did not appear to be required for the interactions, and expression of the major outer-sheath protein (Msp) was not necessary, except for binding Parv. micra. Biofilms of densely packed cells and matrix, up to 40 um in depth, were formed between T. denticola and P. gingivalis on salivary pellicle, with T. denticola cells enriched in the upper layers. Expression of CTLP, but not Msp, was critical for dual-species biofilm formation with P. gingivalis. T. denticola did not form dual-species biofilms with any of the other three periodontal bacterial species under various conditions. Synergy between T. denticola and P. gingivalis was also shown by increased inhibition of blood clotting, which was CTLP-dependent. The results demonstrate the critical role of CTLP in interactions of T. denticola with other oral micro-organisms, leading to synergy in microbial community development and host tissue pathogenesis. PMID- 22313694 TI - Responsibility and ethics in publishing for editors and authors. PMID- 22313693 TI - Defining the "core microbiome" of the microbial communities in the tonsils of healthy pigs. AB - BACKGROUND: Porcine tonsils are the colonization site for many pathogenic as well as commensal microorganisms and are the primary lymphoid tissue encountered by organisms entering through the mouth or nares. The goal of this study was to provide an in-depth characterization of the composition and structure of the tonsillar microbial communities and to define the core microbiome in the tonsils of healthy pigs, using high throughput bar-coded 454-FLX pyrosequencing. RESULTS: Whole tonsils were collected at necropsy from 12 16-week-old finisher pigs from two healthy herds. Tonsil brushes were also used to collect samples from four of these animals. Bacterial DNA was isolated from each sample, amplified by PCR with universal primers specific for the bacterial 16S rRNA genes, and the PCR products sequenced using pyrosequencing. An average of 13,000 sequences were generated from each sample. Microbial community members were identified by sequence comparison to known bacterial 16S rRNA gene sequences.The microbiomes of these healthy herds showed very strong similarities in the major components as well as distinct differences in minor components. Pasteurellaceae dominated the tonsillar microbiome in all animals, comprising ~60% of the total, although the relative proportions of the genera Actinobacillus, Haemophilus, and Pasteurella varied between the herds. Also found in all animals were the genera Alkanindiges, Peptostreptococcus, Veillonella, Streptococcus and Fusobacterium, as well as Enterobacteriaceae and Neisseriaceae. Treponema and Chlamydia were unique to Herd 1, while Arcanobacterium was unique to Herd 2.Tonsil brushes yielded similar results to tissue specimens, although Enterobacteriaceae and obligate anaerobes were more frequently found in tissue than in brush samples, and Chlamydia, an obligately intracellular organism, was not found in brush specimens. CONCLUSIONS: We have extended and supported our previous studies with 16S clone libraries, using 16S rRNA gene pyrosequencing to describe the microbial communities in tonsils of healthy pigs. We have defined a core microbiome, dominated by Pasteurellaceae, in tonsil specimens, and have also demonstrated the presence of unique minor components of the tonsillar microbiome present in each herd. We have validated the use of non-invasive tonsil brushes, in comparison to tonsil tissue, which will facilitate future studies. PMID- 22313697 TI - Influencing land use planning: making the most of opportunities to work upstream. PMID- 22313698 TI - Strengthening public health engagement in trade policy: PHAA's policy on Trade Agreements and Health. PMID- 22313699 TI - Comparing electronic and paper surveys. PMID- 22313700 TI - A public health approach to bereavement support services in palliative care. PMID- 22313701 TI - The long-term decline of adult tobacco use in Victoria: changes in smoking initiation and quitting over a quarter of a century of tobacco control. AB - OBJECTIVE: To examine changes in regular smoking prevalence among demographic and socioeconomic groups of Victorian adults from 1984 to 2008. METHODS: Data were drawn from face-to-face and telephone surveys of randomly sampled Victorians conducted annually from 1984 to 2008. RESULTS: Regular smoking in Victoria declined from 33.2% in 1984 to 15.5% in 2008, a relative decline of 53%. This change was largely accounted for by significant drops in 'ever smoking' among 18 29 year olds (from 59% to 35%, a relative decline of 41%) and by increased quitting among those aged 30 and older (from a quit proportion [% of those ever smoked who have quit] of 37% to 61% among 30-49 year olds, a relative increase of 64%; and from 53% to 79% among 50+ years, an increase of 48%). Over time, smoking prevalence became more similar between males and females. Regular smoking declined significantly across all socioeconomic status (SES) groups. Victorians living in low SES areas experienced the greatest relative increase in quit proportions of 75% (from 34% to 60%), helping to reduce the gap between low and higher SES groups in terms of smoking prevalence. CONCLUSIONS: Regular smoking in Victoria has declined substantially across all demographic groups. Victorians are taking up smoking at much lower levels than 25 years ago, while quit proportions have more than doubled. IMPLICATIONS: The continuation and extension of comprehensive, multi-level approaches to tobacco control is likely to be required for the maintenance of the downward trend in smoking. PMID- 22313702 TI - National trends in Aboriginal and Torres Strait Islander smoking and quitting, 1994-2008. AB - OBJECTIVE: To describe the trends in the prevalence of smoking, quitting and initiation among Aboriginal and Torres Strait Islander men and women aged 18 years and over. METHODS: Analysis of responses to smoking questions in national Indigenous surveys in 1994, 2002, 2004 and 2008. RESULTS: Male Indigenous smoking prevalence fell significantly from 58.5% in 1994 to 52.6% in 2008, an absolute decrease of 0.4 (CI 0.1-0.7)% per year, with the same decline in remote and non remote areas. Female smoking fell from 51.0% to 47.4%, with markedly different changes in remote and non-remote areas. In non-remote areas, there was an absolute decrease in female smoking of 0.5 (CI 0.2-0.9)% per year, but in remote areas, female smoking increased by 0.4 (CI 0.0-0.8)% per year. From 2002 to 2008, the percentage of ever-smokers who had quit (quit ratio) increased absolutely by 1% per year in both men and women, remote and non-remote areas. Results about trends in initiation were inconclusive. CONCLUSIONS AND IMPLICATIONS: Health Minister Roxon has committed to halving the Indigenous smoking prevalence by 2018, and has dramatically increased Indigenous-specific funding and activity in tobacco control. The reported historical trends in this paper are encouraging as they occurred at a time when there was little such tobacco control activity focused on Aboriginal and Torres Strait Islander people. However, to meet the Minister's goal, Indigenous smoking prevalence will need to fall more than six times as quickly as occurred from 1994 to 2008. PMID- 22313703 TI - Investigating the use of social media to help women from going back to smoking post-partum. AB - OBJECTIVE: To investigate the social factors that would help women who had quit smoking due to pregnancy from returning to smoking after delivery of their baby. METHODS: Women who attended their first antenatal check-up at a general public hospital were invited to participate in pre- and postpartum interviews. RESULTS: A total of 24 women were interviewed pre- and postpartum. They reported isolation as a factor that influenced how they dealt with stress. This stress was linked to relapse. The use of electronic media through the Internet was a way women could interact with the outside community without having to leave home. CONCLUSIONS: Women who had strong family relationships in geographic proximity were not as likely to use the computer to interact with relatives and friends. Women who did not have strong local and family ties that support their desire to not go back to smoking, reported using Facebook and other Internet activities to keep in touch while they stayed at home with their new infant. IMPLICATIONS: The use of electronic media may help facilitate interaction between new mothers, which could prevent isolation and relapse back to smoking after delivery. This mechanism might also be used to enhance skill-development and problem-solving by these women. PMID- 22313704 TI - Alcohol consumption and intoxication among people involved in police-recorded incidents of violence and disorder in non-metropolitan New South Wales. AB - OBJECTIVE: To describe, based on routinely recorded police data, the prevalence and characteristics of alcohol consumption among people involved in violence and disorder incidents in non-metropolitan New South Wales (NSW). METHODS: A descriptive analysis was conducted of people involved in violence and disorder incidents over 24 months (2003-05) across 21 non-metropolitan police commands. The prevalence of alcohol involvement was reported as: the annual population rate of people involved in incidents who had consumed alcohol; the proportion of people involved in such incidents who had consumed alcohol; and the proportion of such people who were intoxicated. Variation in alcohol involvement was described by: geographic area; day of week; time of day; and location alcohol was last consumed. RESULTS: Annually, one in 118 people in the population consumed alcohol prior to involvement in a violence incident, and one in 476 people did so prior to a disorder incident. At least 71% of such people were intoxicated. Late Saturday evening was the peak time for alcohol involvement. Prior drinking in private residences and licensed premises was associated with violence and disorder incidents (respectively). The prevalence of alcohol consumption rose with increased geographic remoteness. All characteristics displayed geographic variation. CONCLUSIONS: The high prevalence of alcohol consumption, particularly intoxication, in violence and disorder incidents represents a significant public health issue for non-metropolitan NSW. IMPLICATIONS: Geographic variability in the prevalence and characteristics of alcohol-related crime suggests a need for locally targeted, yet evidence-based, interventions to reduce such harm. PMID- 22313705 TI - The social gradient of alcohol availability in Victoria, Australia. AB - OBJECTIVES: To explore the socioeconomic gradient of alcohol availability in Victoria, Australia. METHODS: Using data for the smallest geographic units available, per-capita and area-based measures of alcohol outlet density were calculated for four types of alcohol outlet (broadly: restaurants, hotels, packaged liquor outlets and licensed clubs). These densities were aggregated across deciles of socioeconomic disadvantage, to compare the average density of alcohol outlets across ten levels of socioeconomic status. In addition, negative binomial regression models were developed, assessing the relationship between density and socioeconomic status while controlling for relevant covariates. RESULTS: In urban areas, both takeaway liquor outlets and licensed clubs were significantly more likely to be located in areas of socioeconomic disadvantage, while hotel and restaurant licences were more prevalent in advantaged areas. In rural and regional Victoria, all types of outlet types were more prevalent in areas of socioeconomic disadvantage. CONCLUSIONS: The findings suggest that disparities in exposure to alcohol outlets in Victoria may play a role in explaining socioeconomic disparities in health outcomes, with Victorians living in disadvantaged areas generally faced with higher levels of alcohol availability. PMID- 22313706 TI - Close proximity to alcohol outlets is associated with increased serious violent crime in New Zealand. AB - OBJECTIVE: To examine the association between geographic access to alcohol outlets and serious violent crime in New Zealand. METHODS: A national study of alcohol outlet access and serious violent crime used a cross-sectional ecological analysis. Serious violence offences recorded between 2005 and 2007 were aggregated for 286 police station areas. Using Geographical Information Systems (GIS), 9,320 licensed premises were geocoded and road travel distances to the closest alcohol outlet type/category were calculated for each area. Negative binomial regression models measured the association between the distance to the closest alcohol outlet and the number of serious violent offences in each police station area, controlling for area-level measures of social deprivation, Maori population, young males 15-29 years and population density. RESULTS: There were significant negative associations between distance (access) to licensed outlets and the incidence of serious violent offences with greater levels of violent offending recorded in areas with close access to any licensed premises compared to those areas with least access (IRR 1.5, 95% CI 1.10-2.03); with on-licensed premises (IRR 1.6, 95% CI 1.16-2.08); and off-licensed premises (IRR 1.4, 95% CI 1.05-1.93). CONCLUSION: Having greater geographic access to alcohol outlets was associated with increased levels of serious violent offending across study areas. IMPLICATIONS: Alcohol availability and access promoted under the current liberalised licensing regime are important contextual determinants of alcohol related harm within New Zealand communities. PMID- 22313707 TI - Implementation of effective alcohol control strategies is needed at large sports and entertainment events. AB - OBJECTIVE: To assess the implementation and effectiveness of strategies and actions to eliminate and/or reduce alcohol-related problems at large sports and entertainment events in New Zealand. METHODS: We conducted site visits and monitoring observations at venues before, during and after a variety of large events between March 2009 and November 2010. Thirteen events were attended at nine different venues. Events included rugby, rugby league and cricket matches, motor racing, rowing, horse racing, an outdoor music festival, and food and wine festivals. RESULTS: Most large events appeared to pass with few or no alcohol related problems. The exceptions were one of the horse-race meetings, a rugby league match and one food and wine festival. Common contexts at events where alcohol-related problems were seen included: inadequate alcohol control and management by security staff; the ability to purchase four alcoholic drinks (rather than two) at a time; inexperienced bar staff untrained in responsible alcohol service; no or little promotion of low and non-alcoholic drinks; and a lack of monitoring and enforcement of the law on intoxication. CONCLUSIONS: An important approach to prevent and reduce alcohol-related problems at large spots and entertainment events is the use of specific alcohol-control strategies. The management of alcohol consumption is a major part of event management that must be planned with harm-minimisation strategies well in advance of the event itself. IMPLICATIONS: If strategies and actions are not properly implemented to manage the sale and supply of alcohol at large events, there is significant risk of alcohol-related problems and harm resulting from them. PMID- 22313708 TI - Factors that enable and hinder the implementation of projects in the alcohol and other drug field. AB - OBJECTIVE: Few studies systematically explore elements of successful project implementation across a range of alcohol and other drug (AOD) activities. This paper provides an evidence base to inform project implementation in the AOD field. APPROACH: We accessed records for 127 completed projects funded by the Alcohol, Education and Rehabilitation Foundation from 2002 to 2008. An adapted realist synthesis methodology enabled us to develop categories of enablers and barriers to successful project implementation, and to identify factors statistically associated with successful project implementation, defined as meeting all funding objectives. Thematic analysis of eight case study projects allowed detailed exploration of findings. RESULTS: Nine enabler and 10 barrier categories were identified. Those most frequently reported as both barriers and enablers concerned partnerships with external agencies and communities, staffing and project design. CONCLUSION: Achieving supportive relationships with partner agencies and communities, employing skilled staff and implementing consumer or participant input mechanisms were statistically associated with successful project implementation. IMPLICATIONS: The framework described here will support development of evidence-based project funding guidelines and project performance indicators. The study provides evidence that investing project hours and resources to develop robust relationships with project partners and communities, implementing mechanisms for consumer or participant input and attracting skilled staff are legitimate and important activities, not just in themselves but because they potentially influence achievement of project funding objectives. PMID- 22313709 TI - Description of comprehensive dental services supported by the Medicare Chronic Disease Dental Scheme in the first 23 months of operation. AB - OBJECTIVE: Australia's Medicare universal insurance system has supported comprehensive dental service through the Chronic Disease Dental Scheme (CDDS) since November 2007. Public debate opposing CDDS includes claims of over servicing, calls for expansion to universal eligibility, and government threat of closure. Here we examine CDDS services over the first 23 months of operation. METHODS: CDDS statistics on patient age, gender and item numbers claimed from November 2007 to December 2009 from Medicare were subjected to analysis. RESULTS: The distribution of 404,768 total CDDS patients varied across Australia from 3.6% of the population in NSW to 0.07% in NT, while uptake increased over time. The average patient had 7.58 dental treatments, and the most common were: direct restorations (2.27), preventive and periodontal services (1.46), diagnostic services (1.43), extractions (0.77), and new dentures (0.53). Crown and bridgework appeared over-represented (0.48). CONCLUSION: Although data do suggest over-servicing in crown and bridgework, there also appears to be significant community need for the CDDS. IMPLICATION: Clear guidelines for dental clinical diagnosis and treatment planning, as well as a pre-approval process for crown and bridgework is suggested to improve the CDDS, and this could form the basis for expansion to universal eligibility for dental Medicare. PMID- 22313710 TI - Falling through the cracks: the gap between evidence and policy in responding to depression in gay, lesbian and other homosexually active people in Australia. AB - OBJECTIVE: To examine the evidence for a national policy response to depression among gay, lesbian and other homosexually active people in Australia. METHODS: A literature review using database searches on depression among non-heterosexual people then a web-based search of national policy investigating how mental health needs in this population are addressed in Australia. RESULTS: The literature review found that non-heterosexual people experience depression at higher rates, but the literature on interventions was sparse. The policy analysis found no mention of depression or the broader mental health needs of non-heterosexual people in key national mental health policy documents. These documents outline a policy approach for population groups with a higher prevalence of mental health problems, and stigma and discrimination are relevant associated factors, but only the National Suicide Strategy considers non-heterosexual people an 'at-risk group'. CONCLUSIONS: The results suggest that the evidence on higher rates of depression in non-heterosexual people is strong, but that this is not recognised in current national policy. IMPLICATIONS: Defining non-heterosexual people as an 'at-risk' group is appropriate, as is prioritising access to mental health services that are socially and culturally appropriate. Addressing homophobia as an associated factor would require a strategic policy approach across a range of sectors. PMID- 22313711 TI - Key opportunities for sodium reduction in New Zealand processed foods. AB - OBJECTIVE: To identify key opportunities for reformulation of processed foods that could best decrease population sodium intakes in New Zealand (NZ). METHOD: Relevant national literature and reports were used to identify major food groups contributing to population sodium intakes in NZ. Sodium content data for these food groups were collected from the Nutrition Information Panels of processed foods in one large supermarket. Key opportunities for reformulation were identified by comparing mean sodium content with 2012 targets from the United Kingdom (UK) Food Standards Agency (FSA) and mean sodium values from Australia and the UK. RESULTS: Major contributors to NZ sodium intakes are: bread (26%), processed meats (10%), and sauces (6%). Mean (SD) sodium contents of these processed foods were: 447 (125) mg/100 g, 1,169 (444) mg/100 g, and 1,046 (1,235) mg/100 g, respectively. Food categories with the lowest percentage of products meeting corresponding FSA targets were: sausages/hot dogs and sliced meat (0%); salami/cured meat (2%); liquid meal-based sauces (4%); and multigrain bread (14%). Mean sodium contents of NZ products were higher than for similar products in the UK. Key opportunities identified for sodium reduction were: white bread, sausages and hot dogs, and salami/cured meats. CONCLUSION: There is substantial scope to reduce the sodium content of NZ processed foods. IMPLICATIONS: This paper identifies three key opportunities for reformulation of processed foods that could produce substantial decreases in sodium intakes in NZ, and benefits to population health. PMID- 22313712 TI - Vaccination, public health and national security. PMID- 22313713 TI - Children and adolescent exposure to alcohol advertising during Bathurst 1000. PMID- 22313714 TI - Responses to 'From Norm to Eric': health is about where you live and what happens to you. PMID- 22313715 TI - $870 million budget covers whole National Partnership. PMID- 22313716 TI - Addressing alcohol use in community sports clubs: attitudes of club representatives. PMID- 22313718 TI - Chest trauma in Far North Queensland: alcohol management can make a difference. PMID- 22313719 TI - Is this really an ethical evaluation of HPV vaccination policy in Australia? PMID- 22313720 TI - Lifespan persistence of ADHD: the life transition model and its application. AB - BACKGROUND: The understanding that attention-deficit/hyperactivity disorder (ADHD) often persists throughout life has heightened interest of patients, families, advocates, and professionals in a longitudinal approach to management. Such an approach must recognize and address known patient- and systems-based challenges of long-term mental health treatment, shifting of clinical presentations of ADHD, and commonality of psychiatric comorbidity with ADHD. OBJECTIVE: The ADHD Life Transition Model is a step toward developing criteria to optimize recognition and clinical management of ADHD (eg, response, remission) across an individual's lifespan and across diverse medical subspecialties. To support therapeutic efficiency and adaptability, our proposed model highlights periods when external resources for managing ADHD are reduced, cognitive and behavioral stressors are increased, and individuals may be reevaluating how they perceive, accept, and adhere to ADHD treatment. Such a model aims to support the clinical community by placing in context new findings, which suggest that the prevention of adult psychopathology in individuals with pediatric ADHD may be possible. CONCLUSIONS: The ADHD Life Transition Model seeks to improve care for individuals with ADHD by (1) underscoring that ADHD persists beyond childhood in at least two-thirds of patients, (2) raising awareness of the need to approach ADHD from a chronic illness standpoint, and (3) increasing mental health professionals' diligence in symptom recognition and management of ADHD across developmental phases from childhood through adulthood. PMID- 22313721 TI - Carbon nanotube bumps for the flip chip packaging system. AB - Carbon nanotube [CNT] interconnection bump joining methodology has been successfully demonstrated using flip chip test structures with bump pitches smaller than 150 MUm. In this study, plasma-enhanced chemical vapor deposition approach is used to grow the CNT bumps onto the Au metallization lines. The CNT bumps on the die substrate are then 'inserted' into the CNT bumps on the carrier substrate to form the electrical connections (interconnection bumps) between each other. The mechanical strength and the concept of reworkable capabilities of the CNT interconnection bumps are investigated. Preliminary electrical characteristics show a linear relationship between current and voltage, suggesting that ohmic contacts are attained. PMID- 22313722 TI - Effect of anaerobic digestion temperature on odour, coliforms and chlortetracycline in swine manure or monensin in cattle manure. AB - AIMS: This study evaluated the effect of anaerobic digestion at 22, 38 and 55 degrees C on odour, coliforms and chlortetracycline (CTC) in swine manure or monensin (MON) in cattle manure. METHODS AND RESULTS: Swine or cattle were fed the respective growth promotant, manure was collected, and 2-l laboratory methane digesters were established at the various temperatures and sampled over 25 or 28 days. After 21 days, the concentration of CTC in the 22, 38 and 55 degrees C swine digester slurries decreased 7, 80 and 98%, respectively. Coliforms in the 22 degrees C digester slurries were still viable after 25 days; however, they were not detectable in the 38 and 55 degrees C slurries after 3 and 1 days, respectively. After 28 days, the concentration of MON in the 22, 38 and 55 degrees C cattle digester slurries decreased 3, 8 and 27%, respectively. Coliforms in the 22 degrees C cattle digester slurries were still viable after 28 days; however, they were not detectable in the 38 and 55 degrees C slurries after 14 and 1 days, respectively. CONCLUSIONS: These studies indicate that anaerobic digestion at 38 or 55 degrees C may be an effective treatment to reduce coliforms and CTC; however, it is not an effective treatment to reduce MON. SIGNIFICANCE AND IMPACT OF THE STUDY: More studies are needed to determine which pharmaceuticals are susceptible to degradation by a specific manure treatment to prevent negative environmental consequences. PMID- 22313723 TI - An appraisal of rehabilitation regimes used for improving functional outcome after total hip replacement surgery. AB - This study aimed to systematically review the literature with regards to studies of rehabilitation programmes that have tried to improve function after total hip replacement (THR) surgery. 15 randomised controlled trials were identified of which 11 were centre-based, 2 were home based and 2 were trials comparing home and centre based interventions. The use of a progressive resistance training (PRT) programme led to significant improvement in muscle strength and function if the intervention was carried out early (< 1 month following surgery) in a centre (6/11 centre-based studies used PRT), or late (> 1 month following surgery) in a home based setting (2/2 home based studies used PRT). In direct comparison, there was no difference in functional measures between home and centre based programmes (2 studies), with PRT not included in the regimes prescribed. A limitation of the majority of these intervention studies was the short period of follow up. Centre based program delivery is expensive as high costs are associated with supervision, facility provision, and transport of patients. Early interventions are important to counteract the deficit in muscle strength in the affected limb, as well as persistent atrophy that exists around the affected hip at 2 years post operatively. Studies of early home-based regimes featuring PRT with long term follow up are needed to address the problems currently associated with rehabilitation following THR. PMID- 22313724 TI - Risk of nonaccidental and cardiovascular mortality in relation to long-term exposure to low concentrations of fine particulate matter: a Canadian national level cohort study. AB - BACKGROUND: Few cohort studies have evaluated the risk of mortality associated with long-term exposure to fine particulate matter [<= 2.5 MUm in aerodynamic diameter (PM(2.5))]. This is the first national-level cohort study to investigate these risks in Canada. OBJECTIVE: We investigated the association between long term exposure to ambient PM(2.5) and cardiovascular mortality in nonimmigrant Canadian adults. METHODS: We assigned estimates of exposure to ambient PM(2.5) derived from satellite observations to a cohort of 2.1 million Canadian adults who in 1991 were among the 20% of the population mandated to provide detailed census data. We identified deaths occurring between 1991 and 2001 through record linkage. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for available individual-level and contextual covariates using both standard Cox proportional survival models and nested, spatial random-effects survival models. RESULTS: Using standard Cox models, we calculated HRs of 1.15 (95% CI: 1.13, 1.16) from nonaccidental causes and 1.31 (95% CI: 1.27, 1.35) from ischemic heart disease for each 10-MUg/m(3) increase in concentrations of PM(2.5). Using spatial random-effects models controlling for the same variables, we calculated HRs of 1.10 (95% CI: 1.05, 1.15) and 1.30 (95% CI: 1.18, 1.43), respectively. We found similar associations between nonaccidental mortality and PM2.5 based on satellite-derived estimates and ground-based measurements in a subanalysis of subjects in 11 cities. CONCLUSIONS: In this large national cohort of nonimmigrant Canadians, mortality was associated with long-term exposure to PM(2.5). Associations were observed with exposures to PM(2.5) at concentrations that were predominantly lower (mean, 8.7 MUg/m(3); interquartile range, 6.2 MUg/m(3)) than those reported previously. PMID- 22313725 TI - Extensive Mycobacterium tuberculosis circulation in a highly endemic prison and the need for urgent environmental interventions. AB - Aimed at assessing the circulation of Mycobacterium tuberculosis in a highly endemic prison, this 13-month prospective study was performed on strains isolated from tuberculosis (TB) cases detected passively and actively. We used X-ray screening of newly admitted inmates and mass screening at the beginning of the study and again 1 year later. Of the 94 strains genotyped by restriction fragment length polymorphism, 79 (84.0%) belonged to one of the 12 identified clusters (2 21 strains each), including two main clusters (18 and 21 cases, respectively). A history of TB treatment was reported in 22/79 (27.8%) clustered cases. Time-space distribution of clustered cases was predominantly consistent with transmission, in micro-epidemics. Given the dominant pattern of exogenous infection and the extensive strain circulation, effective TB control should emphasize reduction of overcrowding and improvement of environmental measures as a complement to detection and treatment of cases. PMID- 22313726 TI - Effect of cannabis use on the course of schizophrenia in male patients: a prospective cohort study. AB - BACKGROUND: Findings on the impact of cannabis use on the course of schizophrenia are inconsistent and not conclusive. AIMS: To study the effect of cannabis use on the course of schizophrenia taking into account the effects of the quantity of cannabis use and important confounders. METHODS: Prospective cohort study with assessments of symptoms, confounders and hospitalizations at baseline, 6 month and 12 month follow up. RESULTS: In a representative cohort of 145 male patients with schizophrenia, 68 (46.9%) used cannabis. Mean age at onset of schizophrenia in cannabis using patients was significantly lower than in non-cannabis using patients. No other cross-sectional demographic or clinical differences were observed between users and non-users. In a series of longitudinal analyses, cannabis use was not associated with differences in psychopathology, but relapse in terms of the number of hospitalizations was significantly higher in cannabis using patients compared to non-cannabis using patients. CONCLUSIONS: Patients with schizophrenia using cannabis are more frequently hospitalized than non cannabis using patients but do not differ with respect to psychopathology. Possible explanations for these findings are discussed. PMID- 22313727 TI - The value of extended transurethral resection of bladder tumour (TURBT) in the treatment of bladder cancer. AB - Transurethral resection of bladder tumour (TURBT) is the 'gold standard' in the diagnosis and therapy of non-muscle-invasive bladder cancer. To improve the quality of this technique an additional TUR (after 4-6 weeks) or a simultaneous photodynamic diagnosis is often offered. The present study shows different variables that influence, to a greater or lesser extent, the accuracy of the TUR diagnosis and the success of the operation. This is very important for the further management of bladder cancer, be it in tumour follow-up or in preparation for more invasive therapies. OBJECTIVE: To analyse the impact of a standardised extended transurethral resection of bladder tumour (TURBT) protocol on the determination of the residual tumour status at initial TURBT session and recurrence rate in the primary resection area. Despite, the fact that there is a clear consensus on the aims of TURBT, there is little agreement on how to perform TURBT to achieve that goal. PATIENTS AND METHODS: We retrospectively evaluated 221 consecutive patients, who underwent 305 TURBT sessions for bladder cancer, including patients with recurrent tumours. All the TURBTs were extended by taking additional deep and marginal specimens, according to a standardised protocol. Clinical and histopathological data were retrieved from the patients' records. RESULTS: Across all tumour stages, residual tumour (pR1) was found in 38% of the additionally taken specimens. There was a significant association of pR1 status with tumour stage, grade, and size. Also in the group of non-muscle-invading tumours, the rate of R1 resection was rather high at 22%. There was no association with focality and the training status of the surgeon. At follow-up, of all the patients with a unifocal primary tumour there was recurrence in the same area as the primary in 5.1%. CONCLUSIONS: Extended TURBT provides detailed information about the horizontal and vertical extent of the bladder tumour. The implementation of standardised TURBT procedures, such as our protocol of an extended TURBT, is greatly needed to improve local tumour control. Whether a diagnostic re-TUR may be restricted to those cases with positive margins or ground specimens remains to be studied. PMID- 22313728 TI - Severe postpartum haemorrhage and mode of delivery: a retrospective cohort study. AB - OBJECTIVE: To examine the association between intended mode of delivery and severe postpartum haemorrhage. DESIGN: A retrospective cohort study. SETTING: Material from a nationwide study in Denmark. POPULATION: Danish women giving birth in 2001-08. METHODS: We compared use of red blood cell transfusion by intended mode of delivery in the total population (n = 382 266), in low-risk nulliparous women (n = 147 132) and in women with a previous caesarean delivery (n = 25 156). MAIN OUTCOME MEASURE: Red blood cell transfusion within 7 days of delivery. RESULTS: In the total population the crude transfusion rates for women with planned caesarean delivery and intended vaginal delivery were 2.24 and 1.75%. After adjustment for maternal age, body mass index, birthweight, smoking, parity, number of infants and previous caesarean delivery, the risk of red blood cell transfusion was significantly lower in women with planned caesarean delivery compared with intended vaginal delivery (odds ratio 0.82; 95% CI 0.73-0.92; P < 0.01). In low-risk nulliparous women and in women with a previous caesarean delivery the transfusion rates were lower for planned caesarean delivery compared with intended vaginal delivery before and after adjustment. CONCLUSION: Compared with intended vaginal delivery, planned caesarean delivery was associated with a reduced risk of severe postpartum haemorrhage indicated by use of red blood cell transfusion. PMID- 22313729 TI - The effect of maternal fish oil supplementation during the last trimester of pregnancy on blood pressure, heart rate and heart rate variability in the 19-year old offspring. AB - Studies in experimental animals and human subjects have suggested that intake of n-3 fatty acids in early life can affect cardiovascular risk factors in adult life. Therefore, the aim of the present study was to investigate the effect of fish oil (FO) supplementation during the third trimester of pregnancy on blood pressure (BP), heart rate (HR) and HR variability (HRV) in the 19-year-old offspring. The study was based on follow-up of a randomised, controlled trial from 1990, in which 533 pregnant women were randomised to FO, olive oil (OO) or no oil (NO) during the last trimester of pregnancy. The offspring was invited to a physical examination including BP, HR and HRV measurements. A subgroup consisting of the offspring of mothers with a low baseline fish intake also had 24 h HRV determined. The OO group was used as reference and multiple linear regression modelling was used to compare the FO and OO groups. A total of 180 of the offspring from the FO and OO groups agreed to participate in the study (45%). The adjusted difference between the FO and OO groups was 2 (95% CI -1, 4) mmHg in systolic and 1 (95% CI 0, 3) mmHg in diastolic BP. The difference in HR was 1 (95% CI -2, 4). Also, HRV indices did not differ significantly between groups. Hence, FO supplementation during late pregnancy was not associated with offspring BP, HR and HRV during adolescence. PMID- 22313730 TI - Trans mechanism for ubiquitin-like protein transfer in autophagy. PMID- 22313731 TI - TRPV1 antagonists may exacerbate sepsis in aged mice: should we be nervous? PMID- 22313733 TI - All p65-containing dimers are not equal. PMID- 22313732 TI - Synaptotagmin1 is required for spindle stability and metaphase-to-anaphase transition in mouse oocytes. AB - Synaptotagmin1, a calcium sensor for exocytosis, forms the 7S complex, or so called SNARE protein complex, together with SNAP -25, syntaxin and synaptobrevin to mediate docking and fusion of synaptic vesicles to the plasma membrane of the nerve terminal. Here, we identified the unique localization, expression and function of Syt1 during mouse oocyte meiotic maturation by using confocal microscopy, western blotting, Morpholino-based knockdown and time-lapse live cell imaging. We showed that Syt1 expression was gradually increased during oocyte maturation. Syt1 was localized at the oocyte cortex from GV to MII stages and at the spindle poles in MI and MII phases, with one third of a signal-free zone at the oocyte cortex, where the chromosomes are located, which is similar to the distribution pattern of CGs from the pro-MI to MII stages. Knockdown of Syt1 resulted in pro-MI/MI arrest and PB1 extrusion decrease, with severely disrupted spindles and misaligned chromosomes. Knockdown of Syt1 also caused abnormal localization of gamma-tubulin, which became redistributed into the cytoplasm. Chromosome spreading showed failure of homologous chromosome segregation. The spindle assembly checkpoint protein Bub3 was detected at the kinetochores even after 10 h of oocyte culture. Live cell imaging analysis revealed that knockdown of Syt1 resulted in abnormal spindles with various morphologies and chromosomes arrested at the pro-MI/MI stage. Defective spindles failed to support chromosome alignment along microtubules, which led to repetitive unsuccessful metaphase anaphase transitions and failure of PB1 extrusion after extended culture. Taken together, we suggest that Syt1 may act as a MTOC-associated protein to play important roles in mouse oocyte spindle organization/stability, and that it is indispensable for the metaphase-anaphase transition to promote mouse oocyte meiotic maturation. PMID- 22313734 TI - Dynamic expression of the Robo ligand Slit2 in bone marrow cell populations. AB - The bone marrow (BM) niche is essential for lifelong hematopoietic stem cell (HSC) maintenance, proliferation and differentiation. Several BM cell types, including osteoblast lineage cells (OBC), mesenchymal stem cells (MSC) and endothelial cells (EC) have been implicated in supporting HSC location and function, but the relative importance of these cell types and their secreted ligands remain controversial. We recently found that the cell surface receptors Robo4 and CXCR4 cooperate to localize HSC to BM niches. We hypothesized that Slit2, a putative ligand for Robo4, cooperates with the CXCR4 ligand SDF1 to direct HSC to specific BM niche sites. Here, we have isolated OBC, MSC and EC by flow cytometry and determined their frequency within the bone marrow and the relative mRNA levels of Slit2, SDF1 and Robo4. We found that expression of Slit2 and SDF1 were dynamically regulated in MSC and OBC-like populations following radiation, while Robo4 expression was restricted to EC. Radiation also significantly affected the cellularity and frequency of both the non-adherent and adherent cells within the BM stroma. These data support a physiological role for Slit2 in regulating the dynamic function of Robo-expressing cells within BM niches at steady state and following radiation. PMID- 22313735 TI - Identify the association between polymorphisms of BLK and systemic lupus erythematosus through unlabelled probe-based high-resolution melting analysis. AB - Systemic lupus erythematosus (SLE) is a complex immune disease. The genetic variation in the B lymphoid tyrosine kinase (BLK) gene was found to associate with SLE in Caucasian population. However, the association of rs13277113 and rs4840568 with SLE was not extensively studied in Chinese population. In this study, we aim to test the association of SNP rs13277113 and rs4840568 with the disease risk of SLE in Chinese mainland population. A total of 532 patients with SLE and 576 controls were recruited. Unlabelled probe-based high-resolution melting analysis (HRMA) was used in genotyping. HRMA with unlabelled probe successfully distinguished all genotypes. Significant differences were observed in both genotype and allele frequencies for rs13277113 and rs4840568. Minor alleles of rs13277113 (P = 4.2E-05, odds ratio [OR] 0.66, [95% CI 0.54-0.81]) and rs4840568 (P = 7.1E-05, OR 0.67, [95% CI 0.55-0.82]) were found to be protective against SLE. Polymorphisms of rs13277113 and rs4840568 in BLK gene were associated with SLE in Chinese population. PMID- 22313736 TI - Organ specificity and transcriptional control of metabolic routes revealed by expression QTL profiling of source--sink tissues in a segregating potato population. AB - BACKGROUND: With the completion of genome sequences belonging to some of the major crop plants, new challenges arise to utilize this data for crop improvement and increased food security. The field of genetical genomics has the potential to identify genes displaying heritable differential expression associated to important phenotypic traits. Here we describe the identification of expression QTLs (eQTLs) in two different potato tissues of a segregating potato population and query the potato genome sequence to differentiate between cis- and trans acting eQTLs in relation to gene subfunctionalization. RESULTS: Leaf and tuber samples were analysed and screened for the presence of conserved and tissue dependent eQTLs. Expression QTLs present in both tissues are predominantly cis acting whilst for tissue specific QTLs, the percentage of trans-acting QTLs increases. Tissue dependent eQTLs were assigned to functional classes and visualized in metabolic pathways. We identified a potential regulatory network on chromosome 10 involving genes crucial for maintaining circadian rhythms and controlling clock output genes. In addition, we show that the type of genetic material screened and sampling strategy applied, can have a high impact on the output of genetical genomics studies. CONCLUSIONS: Identification of tissue dependent regulatory networks based on mapped differential expression not only gives us insight in tissue dependent gene subfunctionalization but brings new insights into key biological processes and delivers targets for future haplotyping and genetic marker development. PMID- 22313737 TI - Forkhead box transcription factor, forkhead box A1, shows negative association with lymph node status in endometrial cancer, and represses cell proliferation and migration of endometrial cancer cells. AB - Endometrial cancer is the most common malignancy of the female genital tract and is associated with poor prognosis. It is primarily a hormone-dependent cancer that is regulated by steroid hormones, including estrogen and progesterone. Forkhead box A1 (FOXA1) is a member of the forkhead box transcription factor family and functions as a pioneer factor in estrogen receptor (ER)-positive breast cancer. In the present study, we investigated the expression of FOXA1 in endometrial cancers by immunohistochemical analysis. Nuclear immunoreactivity for FOXA1 was detected in 40 of 109 cases (37%), and was found to be negatively associated with lymph node status (P = 0.033). In ER-positive Ishikawa endometrial cancer cells, small interfering RNA-mediated downregulation of FOXA1 promoted cell proliferation and migration. Furthermore, exogenously introduced FOXA1 suppressed both proliferation and migration of Ishikawa cells. These results suggest that FOXA1 functions as a tumor suppressor through modulation of proliferation and migration of endometrial cancer cells. PMID- 22313738 TI - Differences in crop bacterial community structure between hoatzins from different geographical locations. AB - The hoatzin is the only known folivorous bird with foregut fermentation, and is distributed in Venezuela in rivers of the central savannas to the eastern Orinoco River. Differences in diet are expected to affect the digestive microbiota and we hypothesized that hoatzins from different habitats might have a different crop microbiota. We thus characterized the microbiota of six birds from the Cojedes and Orinoco Rivers using the G2 PhyloChip and, in parallel, we compared plant availability and foraging behavior of the hoatzins from the two locations. Plant composition differed between the 2 locations, which shared 5 out of 18 plant families and 1 plant genus--Coccoloba--that was highly consumed in both locations. The PhyloChip detected ~1600 phylotypes from 42 phyla. There was a core microbiota with ~50% of the OTUs shared by at least 4 of the 6 individuals, but there were also differences in the crop microbiota of animals from the two regions. There existed a higher relative abundance of Alphaproteobacteria and Actinobacteria in the crops of birds from the Cojedes River and of Clostridia and Deltaproteobacteria in the crops of birds from the Orinoco River. The results showed both a core crop microbiota and also the bacterial taxa responsible for geographical differences among individuals from the two locations with different vegetation, suggesting an effect of both diet and geography in shaping the crop bacterial community of the hoatzin. PMID- 22313739 TI - Effect of ginger on acute and delayed chemotherapy-induced nausea and vomiting: a pilot, randomized, open-label clinical trial. AB - BACKGROUND: Nausea and vomiting are among the most prevalent and disturbing side effects of chemotherapy. Therefore, there is a need for additional antiemetic agents that could effectively reduce chemotherapy-induced nausea and vomiting (CINV), whether alone or in combination with current standard therapies. Since clinical data on the effectiveness of ginger in patients with advanced breast cancer is lacking, the present study aimed to evaluate the effects of ginger against both acute and delayed forms of CINV in a population with advanced breast cancer as the main malignancy. METHODS: In this pilot, randomized, open-label clinical trial, 100 women (mean age = 51.83 +/- 9.18 years) with advanced breast cancer who were initially assigned to standard chemotherapy protocol with docetaxel, epirubicin, and cyclophosphamide (the TEC regimen) were randomized to receive ginger (1.5 g/d in 3 divided doses every 8 hours) plus standard antiemetic regimen (granisetron plus dexamethasone; the ginger group) or standard antiemetic regimen alone (control group). The duration of treatment with ginger was specified to 4 days from the initiation of chemotherapy. Prevalence, score, and severity of nausea, vomiting, and retching were assessed using a simplified form of Rhodes index in the first 6 hours, between 6 to 24 hours, and days 2, 3, and 4 postchemotherapy. RESULTS: A significantly lower prevalence of nausea was observed in the ginger group during 6 to 24 hours postchemotherapy. Despite this effect, no other significant additional benefit from ginger (1.5 g/d) was observed against prevalence or severity of nausea, vomiting, and retching in any of the assessed periods. CONCLUSION: Addition of ginger (1.5 g/d) to standard antiemetic therapy (granisetron plus dexamethasone) in patients with advanced breast cancer effectively reduces the prevalence of nausea 6 to 24 hours postchemotherapy. However, there is no other additional advantage for ginger in reducing prevalence or severity of acute or delayed CINV. PMID- 22313740 TI - Optimal mode for maximal aerobic exercise testing in breast cancer survivors. AB - PURPOSE: To determine which mode of exercise is preferred by breast cancer survivors and to evaluate this response between graded exercise testing on a treadmill and on a cycle ergometer. METHODS: Twelve breast cancer survivors completed 2 maximal aerobic stress tests on separate days. The women completed a ramp protocol on an electronically braked cycle ergometer and an incremental step protocol on a treadmill to volitional fatigue. Test order was randomized. Expired gases were collected for the determination of peak aerobic capacity (Vo (2peak)). RESULTS: Exercise mode had a significant effect on the graded exercise response in breast cancer survivors, P = .003. Treadmill Vo (2peak) was significantly greater than bike Vo (2peak) (28.7 +/- 4.7 vs 23.9 +/- 4.7 mL/min/kg, respectively, P = .003) and VE(max) was equivalent between exercise modes (P = .731). Maximal heart rate was significantly higher by 11 bpm during the treadmill protocol (P = .004), and Ve/VCo (2) exhibited possible mode dependency (P = .018). CONCLUSION: This patient population felt more comfortable and produced significantly greater Vo2(peak) values using the treadmill protocol. These results discuss the potential implications concerning the design and interpretation of exercise interventions for breast cancer survivors. PMID- 22313741 TI - Practices, attitudes, and beliefs associated with complementary and alternative medicine (CAM) use among cancer patients. AB - INTRODUCTION: The high prevalence of complementary and alternative medicine (CAM) use among cancer patients (40%-83%) receiving conventional treatment and the complex relationship between the psychosocial factors that may contribute to or result from CAM use requires further understanding. The authors conducted a descriptive mixed-methods pilot study to understand CAM practices, attitudes, and beliefs among cancer patients at the Loma Linda University Medical Center. METHODS: This was the qualitative phase of the study, and no hypotheses were set. A total of 23 face-to-face interviews were conducted, and thematic coding was used to analyze 22 interview transcriptions. There were 14 CAM users (64%) and 8 nonusers (36%). FINDINGS: The themes present among those who used CAM were the following: physicians viewed as one aspect of health care options, a holistic view on well-being, satisfaction with CAM use, and 3 key coping methods (confrontive, supportive, and optimistic) to confront cancer. Themes were not independent of each other. Two themes were present among nonusers; nonusers trusted their physician and were more likely to express evasive coping methods. DISCUSSION: Perceptions and behavioral patterns are complex predictors of CAM use. A better understanding of CAM, medical pluralism, and the perceptions of patients would help health care providers deliver a better quality of care. The promotion of integrative care may help health care providers better identify medical pluralism and would shift focus to patient-centered care. PMID- 22313742 TI - Mechanical, in vitro antimicrobial, and biological properties of plasma-sprayed silver-doped hydroxyapatite coating. AB - Implant-related infection is one of the key concerns in total joint hip arthroplasties. To reduce bacterial adhesion, we used silver (Ag)/silver oxide (Ag(2)O) doping in plasma sprayed hydroxyapatite (HA) coating on titanium substrate. HA powder was doped with 2.0, 4.0, and 6.0 wt % Ag, heat-treated at 800 degrees C and used for plasma spray coating using a 30 kW plasma spray system, equipped with supersonic nozzle. Application of supersonic plasma nozzle significantly reduced phase decomposition and amorphous phase formation in the HA coatings as evident by X-ray diffraction (XRD) study and Fourier transformed infrared spectroscopic (FTIR) analysis. Adhesive bond strength of more than 15 MPa ensured the mechanical integrity of the coatings. Resistance against bacterial adhesion of the coatings was determined by challenging them against Pseudomonas aeruginosa (PAO1). Live/dead staining of the adherent bacteria on the coating surfaces indicated a significant reduction in bacterial adhesion due to the presence of Ag. In vitro cell-material interactions and alkaline phosphatase (ALP) protein expressions were evaluated by culturing human fetal osteoblast cells (hFOB). Our results suggest that the plasma-sprayed HA coatings doped with an optimum amount of Ag can have excellent antimicrobial property without altering mechanical property of the Ag-doped HA coatings. PMID- 22313743 TI - Atypical case of discrete papular mucinosis involving acral and nuchal regions in an adult. PMID- 22313745 TI - Enhanced S-adenosyl-l-methionine production in Saccharomyces cerevisiae by spaceflight culture, overexpressing methionine adenosyltransferase and optimizing cultivation. AB - AIMS: S-adenosyl-l-methionine (SAM) is an important biochemical molecule with great potential in the pharmacological and chemotherapeutic fields. In this study, our aims were to enhance SAM production in Saccharomyces cerevisiae. METHODS AND RESULTS: Through spaceflight culture, a SAM-accumulating strain, S. cerevisiae H5M147, was isolated and found to produce 86.89% more SAM than its ground control strain H5. Amplified fragment length polymorphism (AFLP) analysis demonstrated that there were genetic variations between strain H5M147 and its ground control. Through recombinant DNA technology, the heterologous gene encoding methionine adenosyltransferase was integrated into the genome of strain H5M147. The recombinant strain H5MR83 was selected because its SAM production was increased by 42.98% when compared to strain H5M147. Furthermore, cultivation conditions were optimized using the one-factor-at-a-time and Taguchi methods. Under optimal conditions, strain H5MR83 yielded 7.76 g l(-1) of SAM in shake flask, an increase of 536.07% when compared to the strain H5. Furthermore, 9.64 g l(-1) of SAM was produced in fermenter cultivation. CONCLUSIONS: A new SAM accumulating strain, S. cerevisiae H5MR83, was obtained through spaceflight culture and genetic modification. Under optimal conditions, SAM production was increased to a relative high level in our study. SIGNIFICANCE AND IMPACT OF THE STUDY: Through comprehensive application of multiple methods including spaceflight culture, genetic modification and optimizing cultivation, the yield of SAM could be increased by 6.4 times compared to that in the control strain H5. The obtained S. cerevisiae H5MR83 produced 7.76 g l(-1) of SAM in the flask cultures, a significant improvement on previously reported results. The SAM production period with S. cerevisiae H5MR83 was 84 h, which is shorter than previously reported results. Saccharomyces cerevisiae H5MR83 has considerable potential for use in industrial applications. PMID- 22313744 TI - The predominantly selfing plant Arabidopsis thaliana experienced a recent reduction in transposable element abundance compared to its outcrossing relative Arabidopsis lyrata. AB - BACKGROUND: Transposable elements (TEs) are major contributors to genome evolution. One factor that influences their evolutionary dynamics is whether their host reproduces through selfing or through outcrossing. According to the recombinational spreading hypothesis, for instance, TEs can spread more easily in outcrossing species through recombination, and should thus be less abundant in selfing species. We here studied the distribution and evolutionary dynamics of TE families in the predominantly selfing plant Arabidopsis thaliana and its close outcrossing relative Arabidopsis lyrata on a genome-wide scale. We characterized differences in TE abundance between them and asked which, if any, existing hypotheses about TE abundances may explain these differences. RESULTS: We identified 1,819 TE families representing all known classes of TEs in both species, and found three times more copies in the outcrossing A. lyrata than in the predominantly selfing A. thaliana, as well as ten times more TE families unique to A. lyrata. On average, elements in A. lyrata are younger than elements in A. thaliana. In particular, A. thaliana shows a marked decrease in element number that occurred during the most recent 10% of the time interval since A. thaliana split from A. lyrata. This most recent period in the evolution of A. thaliana started approximately 500,000 years ago, assuming a splitting time of 5 million years ago, and coincides with the time at which predominant selfing originated. CONCLUSIONS: Our results indicate that the mating system may be important for determining TE copy number, and that selfing species are likely to have fewer TEs. PMID- 22313746 TI - Hybrid polymer/ZnO solar cells sensitized by PbS quantum dots. AB - Poly[2-methoxy-5-(2-ethylhexyloxy-p-phenylenevinylene)]/ZnO nanorod hybrid solar cells consisting of PbS quantum dots [QDs] prepared by a chemical bath deposition method were fabricated. An optimum coating of the QDs on the ZnO nanorods could strongly improve the performance of the solar cells. A maximum power conversion efficiency of 0.42% was achieved for the PbS QDs' sensitive solar cell coated by 4 cycles, which was increased almost five times compared with the solar cell without using PbS QDs. The improved efficiency is attributed to the cascade structure formed by the PbS QD coating, which results in enhanced open-circuit voltage and exciton dissociation efficiency. PMID- 22313747 TI - A double mutant between fission yeast telomerase and RecQ helicase is sensitive to thiabendazole, an anti-microtubule drug. AB - In the fission yeast Schizosaccharomyces pombe, deletion of trt1(+) causes gradual telomere shortening, while deletion of pot1(+) causes rapid telomere loss. The double mutant between pot1 and RecQ helicase rqh1 is synthetically lethal. We found that the trt1 rqh1 double mutant was not synthetically lethal. The chromosome end fragments in both the trt1Delta rqh1Delta and the trt1Delta rqh1-hd (helicase dead) double mutants did not enter a pulsed-field electrophoresis gel. Both the trt1Delta rqh1Delta and the trt1Delta rqh1-hd double mutants were sensitive to the anti-microtubule drug thiabendazole. Moreover, the trt1Delta rqh1-hd double mutant displayed RPA foci on the chromosome bridge at high frequency in M phase cells. These phenotypes are very similar to that of the pot1Delta rqh1-hd double mutant, in which recombination intermediates accumulate at the chromosme ends in the M phase. These results suggest that the entangled chromosome ends, most likely recombination intermediates, are present in the M phase in the trt1Delta rqh1-hd double mutant. PMID- 22313748 TI - Molecular cloning, functional expression, and characterization of isolectin genes of hemolytic lectin CEL-III from the marine invertebrate Cucumaria echinata. AB - CEL-III is a hemolytic lectin purified from the marine invertebrate Cucumaria echinata. Previous research has indictated that CEL-III is composed of several isoforms. Here we identified five CEL-III isolectin genes, designated CEL-III-L1, CEL-III-L2, CEL-III-S1, CEL-III-S2, and CEL-III-LS1, by cDNA cloning. The deduced amino acid sequences suggested they shared 94.0-99.8% identical residues. Among the amino acid residues involved in carbohydrate binding, the His residue, which contributes to stacking with sugar, in subdomain 1alpha was replaced by Tyr in CEL-III-L2. The recombinant proteins were expressed in Escherichia coli or insect cells. rCEL-III-L2 showed higher hemolytic activity than those of the other isolectins. Furthermore, an apparent oligomer band of rCEL-III-L2 was detected on erythrocyte membranes, although the other isolectins showed smear bands. These results suggest that Tyr36 of CEL-III-L2 is important for the expression of hemolytic activity and oligomerization. PMID- 22313749 TI - Isolation of uracil auxotrophs of the fungus Acremonium cellulolyticus and the development of a transformation system with the pyrF gene. AB - Acremonium cellulolyticus CF-2612 is a cellulase hyper-producing mutant that originated from A. cellulolyticus Y-94. In this study, we isolated a uracil auxotroph (strain CFP3) derived from CF-2612, and cloned a wild-type pyrF gene encoding orotate phosphoribosyl transferase (OPRTase) from Y-94. OPRTase activity was not detected in strain CFP3, which had one nucleotide substitution in its pyrF gene. The wild-type pyrF gene restored the defective growth of CFP3 on uracil-free medium, and PCR and Southern analyses revealed that wild-type pyrF was integrated into the genome. These results indicate that our transformation system for A. cellulolyticus with the pyrFgene as a selection marker was successful. PMID- 22313750 TI - Effects of Triton X-100 on proton transfer and in the photocycle of archaerhodopsin 4. AB - Archaerhodopsin 4 (AR4), a retinal-containing membrane protein, exhibits a reversed order of proton release and uptake at neutral pH, as compared to the well-known bacteriorhodopsin (BR). In a preceding report, we stated that Triton X 100 solubilized the claret membrane containing AR4 (CM) into monomeric proteins and altered the time order in AR4 at neutral pH. The present study examined the mechanism underlying this phenomenon. We employed a photoelectrochemical cell suitable for observation of the proton pumping behaviors of both the membrane patch and detergent-solubilized proteins over a wide pH range. The pK(a) values of the proton release complex (PRC) in the initial state and the M state were determined with this device. The pK(a) of PRC of monomeric AR4 decreased to a value lower than 7.0 in the photocycle, allowing early proton release at neutral pH. The pK(a) of PRC in the initial state was also strongly affected by solubilization. PMID- 22313751 TI - Yidiyin, a Chinese herbal decoction, improves erectile dysfunction in diabetic patients and rats through the NO-cGMP pathway. AB - The nitric-oxide (NO)-cyclic-guanosine-monophosphate (cGMP) pathway plays a key role in penile erection. Erectile dysfunction (ED) is a complication in male diabetic patients that impacts their quality of 1ife. Recently, Yidiyin, a Chinese herbal decoction, is used to treat diabetic ED, but convincing evidence is lacking, and the potential mechanisms remain uncertain. In the study, diabetic ED patients had low scores on international index of erectile function-5 (IIEF 5), and administration of Yidiyin and hypoglycemic drugs for 16 weeks ameliorated patients' scores on IIEF-5 more than the hypoglycemic drug alone. Moreover, streptozotocin-induced diabetes severely impaired rats' erectile function and the activity of the NO-cGMP pathway in the corpora cavernosum, and treatment with Yidiyin for 4 weeks obviously increased the rats' erectile function, remarkably enhanced the activity of nitric oxide synthase (NOS), and elevated the contents of NO and cGMP. Our findings indicate that Yidiyin improves diabetic ED probably by enhancing the NO-cGMP pathway. PMID- 22313752 TI - Effects of live Lactobacillus paracasei on plasma lipid concentration in rats fed an ethanol-containing diet. AB - The protective effects of live Lactobacillus paracasei NFRI 7415 on alcoholic liver disease were investigated. Male Fischer 344 rats were fed a control diet (CD), an ethanol diet (ED) (35.8% of total energy from ethanol), or an ethanol diet containing 20% live Lb. paracasei NFRI 7415 (10(7) cfu/g) (LD) for 10 weeks. The results indicated that live Lb. paracasei NFRI 7415 reduced the total cholesterol concentration of the plasma and liver in the rats fed the LD. The level of docosahexaenoic acid (DHA; 22:6n-3) in the plasma and liver of the LD group was higher than in the ED group. Chronic alcohol consumption decreased the level of n-3 fatty acid in the plasma and liver of the ED group. These results indicated that live Lb. paracasei NFRI 7415 can adjust the fatty acid composition of the plasma and liver, and that it is possible to decrease liver damage due to chronic alcohol intake. PMID- 22313753 TI - Identification and characterization of genes related to the development of skeletal muscle in the Hainan black goat. AB - In total, 185 unigenes were identified from 380 clones of postnatal skeletal muscle of Hainan Black goats by suppression subtractive hybridization (SSH) technology. Most of the differentially expressed genes involved energy metabolism and muscle contraction. The expression of 19 genes was analyzed in the longissimus dorsi muscles of 2-, 6-, 12-, 24-month olds, and four gene expression patterns were found by hierarchical cluster analysis. Most genes in first expression pattern belonged to myofibrillar proteins and had higher expression levels at 2 months old; genes of the secondary expression pattern had higher expression levels at 12 months old; tropomyoain 1 (alpha) (TPM1) was classified into the third expression pattern, and its expression level showed decreases tendency as age increased. Tropomyoain 2 (beta) (TPM2) was classified into the third expression pattern, which had the opposite expression pattern against TPM1. PMID- 22313754 TI - Influences of aerobic respiration on current generation by Shewanella oneidensis MR-1 in single-chamber microbial fuel cells. AB - In single-chamber microbial fuel cells (SC-MFCs), oxygen molecules diffuse through air cathodes into electrolytes and compete against anodes in accepting electrons. In this study, we constructed multiple gene-knockout mutants for terminal oxidases (SO4607, SO2364, and SO3286) in Shewanella oneidensis MR-1 and examined their abilities to generate electric currents in SC-MFCs. Although single-knockout mutants generated levels of current similar to that of the wild type (WT), an SO4607/SO2364 double-knockout mutant (DO) generated 50% higher current than WT. A triple-knockout mutant did not grow in SC-MFC. The Coulombic efficiencies in SC-MFC were, however, not substantially different between WT and DO. In aerobically grown DO cells, the transcription levels of the genes involved in extracellular electron transfer (mtrC and crp) were increased compared to those in WT cells. These results suggest that suppression of aerobic respiration activates the expression of genes related to the extracellular electron transfer and increases the electric output from SC-MFCs. PMID- 22313755 TI - Secondary metabolites produced by solid fermentation of the marine-derived fungus Penicillium commune QSD-17. AB - The marine sediment-derived fungus Penicillium commune QSD-17 was re-investigated and cultured on rice solid medium. Two new compounds, isophomenone (1) and 3 deacetylcitreohybridonol (2), together with seven known derivatives (3-9), were identified. Their structures were determined by spectroscopic analysis. PMID- 22313756 TI - Optimization of lactobionic acid production by Acetobacter orientalis isolated from Caucasian fermented milk, "Caspian Sea yogurt". AB - We have reported that lactobionic acid is produced from lactose by Acetobacter orientalis in traditional Caucasian fermented milk. To maximize the application of lactobionic acid, we investigated favorable conditions for the preparation of resting A. orientalis cells and lactose oxidation. The resting cells, prepared under the most favorable conditions, effectively oxidized 2-10% lactose at 97.2 to 99.7 mol % yield. PMID- 22313757 TI - Hyuganatsu orange (Citrus tamurana Hort. Ex Tanaka) contains a water soluble substance that suppresses bone loss in ovariectomized rats. AB - We investigated whether Hyuganatsu orange (Citrus tamurana Hort. ex Tanaka) contains water and acetic-acid soluble substances that increase bone mineral density (BMD) in ovariectomized rats. In in vivo study, femoral BMD can significantly increased. In in vitro study, tartrate-resistant acid phosphatase (TRAP) positive cells significantly decreased. We speculate that Hyuganatsu orange contains biologically active substances other than hesperidin that increase BMD. PMID- 22313758 TI - Expression and one-step purification of recombinant proteins using an alternative episomal vector for the expression of N-tagged heterologous proteins in Pichia pastoris. AB - Here we report the construction of an alternative episomal vector, pBGP3, which allows the expression of heterologous proteins with N-terminal hexahistidine and myc-epitope tags in Pichia pastoris. To test the usefulness of pBGP3, four cellulases from termites were expressed. Production was confirmed by activity assays and Western blot using anti-c-Myc antibody. Purification was performed by single-step Ni(2+)-affinity chromatography, which confirmed the efficiency of pBGP3. PMID- 22313759 TI - Algicidal activity of glycerolipids from brown alga Ishige sinicola toward red tide microalgae. AB - Bioassay-guided fractionation of a methanol extract of the brown alga, Ishige sinicola, led to the isolation of five algicidal compounds. Their structures were determined to be alpha-monoglycerides of eicosa-5Z,8Z,11Z,14Z-tetraenoic (arachidonic) acid, octadeca-6Z,9Z,12Z,15Z-tetraenoic acid, linoleic acid and oleic acid, and 1-O-palmitoyl-3-O-(6-sulfo-alpha-D-quinovopyranosyl)-sn-glycerol on the basis of spectroscopic data and a comparison with the data in the literature. These glycerolipids showed moderate-to-high cell lysis activity against the red tide microalgal species, Heterosigma akashiwo, Karenia mikimotoi and Alexandrium catenella, at a concentration of 20 ug/mL. PMID- 22313760 TI - Effect of D-alanine in teichoic acid from the Streptococcus thermophilus cell wall on the barrier-protection of intestinal epithelial cells. AB - D-Alanylation of teichoic acid (TA) affects various functions of Gram-positive bacteria, including immunomodulatory effects. We investigated in this study the impact of D-alanine (D-Ala) in TA from Streptococcus thermophilus ATCC 19258(T) on the barrier-protecting effect in human intestinal Caco-2 cells. ATCC 19258(T) suppressed the tumor necrosis factor-alpha-induced decrease in transepithelial electrical resistance (TER), an indicator of the barrier function. The D alanylation of TA in ATCC 19258(T) was growth phase- and culture temperature dependent. Treatment of ATCC 19258(T) with Mg(2+) decreased the dlt mRNA expression and D-Ala content in TA and also abolished the suppressive effect on the TER decrease. Supplementation with L-alanine (L-Ala) to the broth led to an increase of D-Ala in ATCC 19258(T) and of the intestinal barrier-protecting effect. Taken together, D-Ala in TA played an important role in the barrier protecting effect of S. thermophilus in the intestinal epithelium, and these beneficial effects could be enhanced by exogenous L-Ala. PMID- 22313762 TI - Effects of a lactobacilli, oligosaccharide and organic germanium intake on the immune responses of mice. AB - The organic germanium compound, Ge-132, has immune-modulating effects. We evaluated the symbiotic effects of Ge-132 with lactobacilli and oligosaccharide (LB/OS) on the immune responses of mice. The highest fecal IgA levels were observed in the mice receiving a low concentration of Ge-132 with LB/OS for 8 weeks. Our data suggest that LB/OS with a low concentration of Ge-132 stimulated the intestinal immunity. PMID- 22313761 TI - Inhibitory effects of actinidiamide from Actinidia polygama on allergy and inflammation. AB - Actinidia polygama Max. was subjected to supercritical fluid extraction (SFE), and the resulting ethanol extract of marc (SFEM) was subjected to sequential fractionation with various solvents. Each extract and fraction was assayed for anti-inflammatory effect. The ethyl acetate fraction (EtOAc) contained the highest level (70.8% inhibition) of anti-inflammatory activity. In order to identify the active constituents, the EtOAc fraction was further fractionated by silica gel and ODS column chromatography. By activity-guided fractionation, an active ceramide was identified as the anti-inflammatory component, and its structure was determined by NMR and MS analysis. The novel ceramide was named actinidiamide, and was found significantly to inhibit nitric oxide (NO) production (30.6% inhibition at 1 ug/mL) in lipopolysaccaride (LPS)-stimulated RAW 264.7 cells and beta-hexosaminidase release (91.8% inhibition at 1 ug/mL) in IgE-sensitized RBL-2H3 cells. Thus the presence of actinidiamide conveys allergy and inflammation treatment ability to A. polygama. PMID- 22313763 TI - RNA interference-mediated growth control of the southern root-knot nematode Meloidogyne incognita. AB - The Southern root-knot nematode Meloidogyne incognita causes huge crop losses. We investigated the effects of RNA interference directed against the M. incognita posterior segregation-1 gene. The RNAi resulted in a drastic reduction in the relative amount of pos-1 transcript. Also, it reduced reproductive potential in terms of hatching rate from eggs, probably due to embryonic lethality. PMID- 22313764 TI - Western blot analysis of neisserial lipooligosaccharide at the lower femtomole level with normal human sera. AB - Lipooligosaccharide (LOS) is a major immunogenic component of pathogenic Neisseria species such as Neisseria meningitidis and N. gonorrhoeae. Recent immunochemical studies have found that normal human sera (NHS) contain bactericidal anti-LOS antibodies that bind to the oligosaccharide (OS) moiety of neisserial LOS. Although affinity-purified anti-LOS antibodies can be characterized using 10-100 ng of LOS samples (up to a few tens of pmoles), a more sensitive immunoblotting assay must be established in order to analyze NHS directly and characterize anti-LOS antibodies without affinity purification. We examined analytical PAGE/blot conditions using a 15-well mini gel. For the first time, Western blot detection of LOS at the lower femtomole level was accomplished by both chromogenic and chemiluminescent detection. A model LOS, 15253 LOS, was detected in a low femtomole range (62.5-500 pg, 16-125 femtomole) even with 10 pM of a monoclonal antibody (MAb) 2C7. Furthermore, detection of similar amounts (50 250 femtomole) of neisserial LOSs and Salmonella truncated lipopolysaccharides (LPSs) was also possible with 1:50 and with 1:100 diluted NHS. The results obtained here indicate that the binding of IgG in NHS to the LOS and LPS samples is probably due to their carbohydrate moieties. The detection level accomplished in this study should help not only to further characterize anti-LOS antibodies in blood and body fluids but also to analyze carbohydrate structures that are recognized by them. PMID- 22313765 TI - alpha-Tocopherol sensitizes human leukemia HL-60 cells to apoptosis induced by benzyl isothiocyanate. AB - Pre-treatment with alpha-tocopherol (alpha-Toc) potentiated cytotoxicity induction by benzyl isothiocyanate (BITC). Biochemical events related to apoptosis, such as DNA ladder formation and caspase-3 activation, were also enhanced by alpha-Toc. These results suggest a significant role of the caspase-3 pathway in apoptosis induction regulated by alpha-Toc in combination. PMID- 22313766 TI - Streptomyces nodosus host strains optimized for polyene glycosylation engineering. AB - The AmphDI glycosyltransferase transfers a mycosaminyl sugar residue from GDP onto 8-deoxyamphoteronolide B, the aglycone of the antifungal amphotericin B. In this study the amphDI gene was inactivated in Streptomyces nodosus strains lacking the AmphN cytochrome P450. The new mutants produced 8-deoxy-16-methyl-16 descarboxyl amphoteronolides in high yield. These strains and aglycones should prove valuable for in vivo and in vitro glycosylation engineering. PMID- 22313767 TI - A rapid and simple method of evaluating the dimeric tendency of fluorescent proteins in living cells using a truncated protein of importin alpha as fusion tag. AB - Enhanced green fluorescent protein (EGFP) and its yellow variant (Venus) are weakly dimeric under physiological conditions. We designed a simple method to evaluate the dimeric tendency of fluorescent proteins in living mammalian cells. A novel single mutation, A206L, interfering with the hydrophobic interactions of the dimer interface in Venus, contributed to its monomerization, and was as effective as the A206K mutation in this assay. PMID- 22313768 TI - Msn5p is involved in formaldehyde resistance but not in oxidative stress response in the methylotrophic yeast Candida boidinii. AB - Methylotrophic yeasts, which can utilize methanol as sole carbon and energy source, are exposed to two toxic metabolic intermediates, formaldehyde and hydrogen peroxide, during growth on methanol. Here we report that Msn5p, an importin-beta family nuclear exporter, participated in the formaldehyde resistance mechanism but not in the hydrogen peroxide resistance mechanism in Candida boidinii. Disruption of the MSN5 gene in this yeast caused retardation of growth on formaldehyde-generating growth substrates such as methanol and methylamine, but the expression levels of the methanol-metabolizing enzymes did not fall. The Msn5p-depleted strain was sensitive to formaldehyde but not to hydrogen peroxide. Furthermore, a yellow fluorescent protein-tagged Msn5p was diffuse in the cytoplasm of C. boidinii when the cells were treated with high concentrations of formaldehyde or ethanol, but was predominantly associated with the nuclei following treatment with hydrogen peroxide. PMID- 22313769 TI - Identification and expression analysis of arbuscular mycorrhiza-inducible phosphate transporter genes of soybean. AB - Soybeans, the world's leading leguminous crop, establish mutualistic symbiosis with arbuscular mycorrhizal (AM) fungi. AM fungi colonize root cortical cells forming arbuscules, highly branched fungal structures. Arbuscules are enveloped by plant-derived periarbuscular membranes through which plants obtain mineral nutrients, particularly phosphate. We searched the soybean genome in silico, and found 14 Pht1 genes encoding phosphate transporters putatively localized on the plasma membranes. Time course analyses involving reverse transcription-PCR indicated that three of these were AM-inducible. GmPT10 and GmPT11 were induced on fungal colonization, while a transcript of GmPT7 appeared in the later stages. The transport activities of GmPT10 and GmPT11 were confirmed by complementation of a yeast mutant. Soybean hairy roots expressing the GmPT10-green fluorescent protein (GFP) or GmPT11-GFP fusion protein under the control of corresponding promoter showed GFP fluorescence on the branch domains of periarbuscular membranes, indicating that active phosphate transport occurred there. PMID- 22313770 TI - Effect of chloride ions on anthrasesamone C production in a Sesamum indicum hairy root culture and identification of the precursor for its abiotic formation. AB - The content of anthrasesamone C (5), a rare chlorine-containing anthraquinone, in a hairy root culture of Sesamum indicum increased with increasing chloride ion concentration in the culture medium and reached a maximum at 100 mM. However, the amount of anthrasesamone C (5) in the extract obtained from the hairy roots was increased by incubating the extract. This result suggests that anthrasesamone C (5) was produced from an unidentified metabolite by an abiotic process. 2,3 Epoxyanthrasesamone B (1), a precursor for the non-enzymatic formation of anthrasesamone C (5), was isolated from S. indicum hairy roots cultured in a chloride-deficient medium. Its structure was elucidated to be 2,3-epoxy-9,10 dihydroxy-2-(4-methylpent-3-en-1-yl)-2,3-dihydroanthracene-1,4-dione by spectroscopic methods. PMID- 22313771 TI - Analysis of free fatty acids in sake by an enzymatic method and its application for estimating ethyl caproate and selecting yeast with high productivity of the ester. AB - We show that the concentration of total free fatty acids (FFAs) in sake produced by yeast with high productivity of ethyl caproate could be approximated by the concentration of 2 FFAs, caproic and caprylic acids. Measurement of the total FFAs concentration by an enzymatic method proved useful for both estimating the ethyl caproate concentration in sake and also for yeast breeding. PMID- 22313772 TI - Antioxidative properties of vanillic acid esters in multiple antioxidant assays. AB - The antioxidative properties of vanillic acid esters were systematically evaluated by multiple assays to compare with the well-known antioxidants, vanillic acid and Trolox. We first performed assays with the model radicals, DPPH, galvinoxyl and ABTS cation (ABTS(*+)) types. Methyl vanillate, ethyl vanillate and butyl vanillate showed stronger activity than Trolox in the ABTS(*+)-scavenging assay, but showed no activity in the DPPH radical- and galvinoxyl radical-scavenging assays. In contrast, vanillic acid could quench the three radicals. We then evaluated their antioxidative activities by an ORAC assay and an oxidative hemolysis inhibition assay (OxHLIA), using physiologically relevant peroxyl radicals. Vanillic acid esters and vanillic acid exerted much stronger activity than Trolox in the ORAC assay and OxHLIA. The antioxidative activity by OxHLIA was strongly correlated to the lipophilicity of vanillic acid and its esters. These results indicate that the protective effect of vanillic acid esters against free radical-induced biomembrane damage increased with increasing lipophilicity. PMID- 22313773 TI - Specific expression of the vacuolar iron transporter, TgVit, causes iron accumulation in blue-colored inner bottom segments of various tulip petals. AB - Several flowers of Tulipa gesneriana exhibit a blue color in the bottom segments of the inner perianth. We have previously reported the inner-bottom tissue specific iron accumulation and expression of the vacuolar iron transporter, TgVit1, in tulip cv. Murasakizuisho. To clarify whether the TgVit1-dependent iron accumulation and blue-color development in tulip petals are universal, we analyzed anthocyanin, its co-pigment components, iron contents and the expression of TgVit1 mRNA in 13 cultivars which show a blue color in the bottom segments of the inner perianth accompanying yellow- and white-colored inner-bottom petals. All of the blue bottom segments contained the same anthocyanin component, delphinidin 3-rutinoside. The flavonol composition varied with cultivar and tissue part. The major flavonol in the bottom segments of the inner perianth was rutin. The iron content in the upper part was less than that in the bottom segments of the inner perianth. The iron content in the yellow and white petals was higher in the bottom segment of the inner perianth than in the upper tissues. TgVit1 mRNA expression was apparent in all of the bottom tissues of the inner perianth. The result of a reproduction experiment by mixing the constituents suggests that the blue coloration in tulip petals is generally caused by iron complexation to delphinidin 3-rutinoside and that the iron complex is solubilized and stabilized by flavonol glycosides. TgVit1-dependent iron accumulation in the bottom segments of the inner perianth might be controlled by an unknown system that differentiated the upper parts and bottom segments of the inner perianth. PMID- 22313774 TI - A historical perspective for the catalytic reaction mechanism of glycosidase; so as to bring about breakthrough in confusing situation. AB - Various catalytic reaction models have been proposed as the reaction mechanisms of glycosidases, but a reasonable and unitary model capable of interpreting both "inverting" and "retaining" glycosidase reactions remains to be established. As for the models proposed to date, the nucleophilic displacement mechanism and the oxocarbenium ion intermediate mechanism are widely known, but recently the former is widely accepted, and so the general tendency of world opinion appears to favor it. This reaction model, however, is considered to comprise some inconsistencies that cannot be neglected from the viewpoint of reactivity in organic chemistry. While the nucleophilic displacement mechanism is often applied to reactions of glycosidases, it appears unlikely that such reactions actually occur. This review argues that the oxocarbenium ion intermediate reaction mechanism is more rational than the nucleophilic displacement reaction mechanism, as the action mode of glycosidases and related enzymes. PMID- 22313775 TI - Mutants of Lactobacillus plantarum ML11-11 deficient in co-aggregation with yeast exhibited reduced activities of mixed-species biofilm formation. AB - Lactic acid bacteria (LAB) mutants deficient in inter-species co-aggregation with yeast were spontaneously derived from Lactobacillus plantarum ML11-11, a significant mixed-species biofilm former in static co-cultures with budding yeasts. These non-co-aggregative mutants also showed significant decreases in mixed-species biofilm formation. These results suggest the important role of co aggregation between LAB and yeast in mixed-species biofilm formation. Cell surface proteins obtained by 5 M LiCl extraction from the wild-type cells and non co-aggregative mutant cells were analyzed by SDS-PAGE. There was an obvious difference in protein profiles. The protein band at 30 kDa was present abundantly in the wild-type cell surface fraction but was significantly decreased in the mutant cells. This band assuredly corresponded to the LAB surface factors that contribute to co-aggregation with yeasts. PMID- 22313776 TI - Antioxidative properties of functional polyphenols and their metabolites assessed by an ORAC assay. AB - We compared the antioxidative activities of polyphenol metabolites with those of intact functional polyphenols by an assay of the oxygen radical absorbance capacity (ORAC). The metabolites of ellagitannin geraniin, chlorogenic acid, and (-)-epigallocatechin gallate displayed more potent antioxidative activity than their respective original compounds. Our findings suggest that these metabolites may play important roles as biological antioxidants after their consumption. PMID- 22313777 TI - Changes in the texture and viscoelastic properties of bread containing rice porridge during storage. AB - The objective of this study was to investigate the effects of rice porridge on the texture and viscoelastic properties of bread during storage. Three types of bread, wheat flour bread, 15% rice flour bread, and 15% rice porridge bread, were prepared. After baking and storing the bread for 24 h, 48 h, and 72 h at room temperature, we measured the texture and viscoelastic properties of the bread crumbs by texture profile analysis (TPA) and creep test. The 15% rice porridge bread showed a significantly higher specific volume and maintained softer crumbs than the other two types (p<0.05). It also had a slightly stickier texture than the others. It can be concluded that rice porridge improves the specific volume, texture, and viscoelastic properties of bread crumbs during storage. PMID- 22313778 TI - Development of an enzyme-linked immunosorbent assay system for the determination of asymmetric dimethylarginine using a specific monoclonal antibody. AB - We produced a monoclonal antibody (mAb) against N(G),N(G)-dimethyl-L-arginine (asymmetric dimethylarginine: ADMA), an endogenous competitive inhibitor of nitric oxide synthase (NOS), and developed an enzyme-linked immunosorbent assay (ELISA). The competitive ELISA method using the mAb determined 5 nM-100 nM ADMA, and ADMA levels in human plasma and urine were found to be 0.78 uM and 51.3 umol/g of creatinine respectively. PMID- 22313779 TI - Characterization of a new alpha-galactosyl-binding lectin from the mushroom Clavaria purpurea. AB - A galactose specific lectin (CpL) was purified from the Clavaria purpurea mushroom by affinity chromatography. CpL agglutinated only trypsin-treated rabbit erythrocytes. On enzyme linked lectin sorbent assay (ELLSA), the lectin bound with thyroglobulin and asialo bovine submaxillary mucin (BSM). The fine sugar binding specificity of CpL was elucidated using inhibition of hemagglutination and sugar immobilized gold nano-particles (SGNP). The results indicated a preference of CpL towards alpha-galactosyl sugar chains. Among several monosaccharides and disaccharides assayed for dissociation effect on the SGNP-CpL complex, Galalpha1-3Gal and raffinose were the best inhibitors. The partial amino acid sequence showed two QXW motifs in CpL and similarity towards members of the ricin B superfamily. PMID- 22313780 TI - Antibacterial activity of the lactoperoxidase system combined with edible Laminaria hot-water extract as a source of halide ions. AB - Hot-water extracts prepared from nine out of 12 samples of dried edible Laminaria reduced the viable numbers of Aggregatibacter actinomycetemcomitans, Staphylococcus aureus, and Esherichia coli below the detection limit after incubation for 5 min when combined with lactoperoxidase, glucose oxidase, and glucose. Some extracts showed higher bactericidal activity and a higher OI(-) concentration in the assay mixture after ultrafiltration. PMID- 22313781 TI - Metathesis-mediated synthesis of (R)-10-methyl-2-tridecanone, the southern corn rootworm pheromone. AB - (R)-10-Methyl-2-tridecanone, the female sex pheromone of the southern corn rootworm (Diabrotica undecimpunctata howardi Barber), was synthesized in 9 steps from methyl (S)-3-hydroxy-2-methylpropanoate in a 15.7% overall yield. Olefin cross metathesis between (R)-6-methyl-1-nonene and 5-hexen-2-one employing Grubbs' first-generation catalyst was the key step of the synthesis. PMID- 22313782 TI - Temperature-dependent self-splicing group I introns in the flagellin genes of the thermophilic Bacillus species. AB - A previous report described the presence of a self-splicing group I intron in a flagellin gene from a thermophilic Bacillus species. Here, we present evidence that the splicing reaction of the flagellin introns is dependent on temperature. Furthermore, a complementation analysis using a Bacillus subtilis flagellin deficient mutant indicated that the intron-containing flagellin gene significantly restored the motility of the mutant at higher temperatures. PMID- 22313783 TI - Identification of a degradation intermediate of the momilactone A rice phytoalexin by the rice blast fungus. AB - We have already shown that major rice diterpene phytoalexin, momilactone A, was detoxified by Magnaporthe oryzae. We report here the identification by NMR, MS, and chemical synthesis of 3,6-dioxo-19-nor-9beta-pimara-7,15-diene (1) as the degradation intermediate. Compound 1 exhibited similar antifungal activity to that of momilactone A, indicating 1 to be a precursor of possible detoxified compounds. PMID- 22313784 TI - Characterization of a bacterial laminaribiose phosphorylase. AB - Bacterial laminaribiose phosphorylase (LBP(bac)) was first identified and purified from cell-free extract of Paenibacillus sp. YM-1. It phosphorolyzed laminaribiose into alpha-glucose 1-phosphate and glucose, but did not phosphorolyze other glucobioses. It slightly phosphorolyzed laminaritriose and higher laminarioligosaccharides. The specificity of the degree of polymerization of the substrate was clearly different from that of the enzyme of Euglena gracilis (LBP(Eug)): LBP(bac) was more specific to laminaribiose than LBP(Eug). It showed acceptor specificity in reverse phosphorolysis similar to LBP(Eug). Cloning of the gene encoding LBP(bac) (lbpA) has revealed that LBP(bac) is a member of the glucoside hydrolase family 94, which includes cellobiose phosphorylase, cellodextrin phosphorylase, and N,N'-diacetylchitobiose phosphorylase. The genes that encode the components of an ATP-binding cassette sugar transporter specific to laminarioligosaccharides were identified upstream of lbpA, suggesting that the role of LBP(bac) is to utilize laminaribiose generated outside the cell. This role is different from that of LBP(Eug), which participates in the utilization of paramylon, the intracellular storage 1,3-beta glucan. PMID- 22313785 TI - Relationship between the structures of taxane derivatives and their microtubule polymerization activity. AB - Paclitaxel (Taxol), one of the most potent anticancer drugs, is a microtubule stabilizing compound that inhibits microtubule depolymerization within the cell. The structure of paclitaxel is composed of two key elements, a taxane ring and an N-benzoylphenylisoserine side chain at C-13. A number of natural and artificial compounds with taxane skeletons have been isolated, but almost none of their bioactivities have been evaluated. In this study, we focused on compounds having a taxane skeleton structure and examined their effects on tubulin dynamics. Although none of these compounds had an N-benzoylphenylisoserine side chain, three were found to promote tubulin assembly. On the other hand, one compound inhibited tubluin assembly in a way similar to nocodazole. These compounds exhibited novel structure-activity relationships of taxane compounds. PMID- 22313786 TI - Isolation of borrelidin as a phytotoxic compound from a potato pathogenic streptomyces strain. AB - Streptomyces species strain GK18, isolated in Iran, induced deep-pitted lesions on potato tubers, lesions different from the raised lesions induced by the usual scab-causing phytotoxin, thaxtomin. In addition, neither thaxtomin production nor hybridization to its biosynthetic probe was detected for strain GK18, suggesting the production of a different phytotoxin. The active component was extracted with ethyl acetate from culture filtrate of strain GK18, purified by gel filtration and silica gel chromatography, and identified as an 18-membered macrolide, borrelidin, by spectroscopic analysis. The purified borrelidin induced necrosis on potato tuber slices and inhibited the growth of shoots and roots of radish seedlings. This is the first report on the phytotoxicity of borrelidin as a possible causative compound of potato scab disease. PMID- 22313787 TI - Crystal structures of glycoside hydrolase family 51 alpha-L-arabinofuranosidase from Thermotoga maritima. AB - alpha-L-Arabinofuranosidase from the hyperthermophilic bacterium Thermotoga maritima (Tm-AFase) is an extremely thermophilic enzyme belonging to glycoside hydrolase family 51. It can catalyze the transglycosylation of a novel glycosyl donor, 4,6-dimethoxy-1,3,5-triazin-2-yl (DMT)-beta-D-xylopyranoside. In this study we determined the crystal structures of Tm-AFase in substrate-free and complex forms with arabinose and xylose at 1.8-2.3 A resolution to determine the architecture of the substrate binding pocket. Subsite -1 of Tm-AFase is similar to that of alpha-L-arabinofuranosidase from Geobacillus stearothermophilus, but the substrate binding pocket of Tm-AFase is narrower and more hydrophobic. Possible substrate binding modes were investigated by automated docking analysis. PMID- 22313788 TI - An 8-week, randomized controlled trial of atomoxetine, atomoxetine plus buspirone, or placebo in adults with ADHD. AB - OBJECTIVE: To examine the efficacy and safety of atomoxetine combined with buspirone versus atomoxetine monotherapy and placebo in adult attention deficit/hyperactivity disorder (ADHD). METHOD: In this randomized, 8-week, 3-arm, double-blind, placebo-controlled trial conducted from November 2004 through December 2005, 241 adults with ADHD were randomly assigned in a 2:2:1 ratio to receive up to twice-daily atomoxetine and thrice-daily buspirone (n = 97), twice daily atomoxetine (n = 97), or placebo (n = 47). Participants met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for ADHD. The primary efficacy measure was the adult ADHD Investigator Symptom Rating Scale (AISRS). RESULTS: Decrease in the AISRS total score was significantly greater for atomoxetine-buspirone than placebo at all time points from weeks 1 to 7, with an estimated mean difference of -4.80 (P = .001). Reduction in the mean AISRS total score was numerically greater for atomoxetine buspirone than for atomoxetine at all time points, but statistically significant at week 4 only (estimated difference = -2.04, P < .10). The effect size for atomoxetine plus buspirone was 0.51, and for atomoxetine alone, it was 0.40. Insomnia, nausea, dry mouth, headache, and asthenia were frequently reported adverse events for both active treatment groups, and dizziness was also frequently reported for the atomoxetine-buspirone group. Discontinuations due to treatment-related adverse effects were 15.5% for atomoxetine-buspirone, 11.3% for atomoxetine, and 14.9% for placebo. CONCLUSIONS: There was little indication of improvement for atomoxetine plus buspirone versus atomoxetine monotherapy, as most efficacy measures showed only slightly greater quantitative improvement for the combination, generally without statistical significance. It is of note, however, that the quantitative differences between these 2 groups were virtually all in the direction of greater efficacy for the atomoxetine plus buspirone group. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00174226. PMID- 22313789 TI - Measles outbreak in an asylum-seekers' shelter in Germany: comparison of the implemented with a hypothetical containment strategy. AB - In order to contain a measles outbreak in a German asylum-seekers' shelter, serological testing of all residents was performed, followed by selective vaccination of those with negative test results/not tested. In this paper we describe the outbreak epidemiologically and then compare the implemented strategy with a hypothetical mass vaccination of all individuals unvaccinated or with unknown vaccination status born after 1970 as recommended by the German Standing Committee on Vaccination in terms of potentially avoided cases, logistics, and costs. Three hundred (70%) residents participated in the serological testing, of which 39 (13%) were seronegative. In total, 144 individuals were eligible for vaccination, while a mass vaccination would have targeted 359 persons. However, serological testing was time- and personnel consuming and revealed several logistical problems. Its costs amounted to ?90 000, double that of mass vaccination that additionally might have avoided three of the eight cases. Mass vaccination seems the preferred measure for measles outbreak control in such settings. PMID- 22313790 TI - Prenatal lead levels, plasma amyloid beta levels, and gene expression in young adulthood. AB - BACKGROUND: Animal studies suggest that early-life lead exposure influences gene expression and production of proteins associated with Alzheimer's disease (AD). OBJECTIVES: We attempted to assess the relationship between early-life lead exposure and potential biomarkers for AD among young men and women. We also attempted to assess whether early-life lead exposure was associated with changes in expression of AD-related genes. METHODS: We used sandwich enzyme-linked immunosorbent assays (ELISA) to measure plasma concentrations of amyloid beta proteins Abeta40 and Abeta42 among 55 adults who had participated as newborns and young children in a prospective cohort study of the effects of lead exposure on development. We used RNA microarray techniques to analyze gene expression. RESULTS: Mean plasma Abeta42 concentrations were lower among 13 participants with high umbilical cord blood lead concentrations (>= 10 MUg/dL) than in 42 participants with lower cord blood lead concentrations (p = 0.08). Among 10 participants with high prenatal lead exposure, we found evidence of an inverse relationship between umbilical cord lead concentration and expression of ADAM metallopeptidase domain 9 (ADAM9), reticulon 4 (RTN4), and low-density lipoprotein receptor-related protein associated protein 1 (LRPAP1) genes, whose products are believed to affect Abeta production and deposition. Gene network analysis suggested enrichment in gene sets involved in nerve growth and general cell development. CONCLUSIONS: Data from our exploratory study suggest that prenatal lead exposure may influence Abeta-related biological pathways that have been implicated in AD onset. Gene network analysis identified further candidates to study the mechanisms of developmental lead neurotoxicity. PMID- 22313791 TI - Changing clothes easily: connexin41.8 regulates skin pattern variation. AB - The skin patterns of animals are very important for their survival, yet the mechanisms involved in skin pattern formation remain unresolved. Turing's reaction-diffusion model presents a well-known mathematical explanation of how animal skin patterns are formed, and this model can predict various animal patterns that are observed in nature. In this study, we used transgenic zebrafish to generate various artificial skin patterns including a narrow stripe with a wide interstripe, a narrow stripe with a narrow interstripe, a labyrinth, and a 'leopard' pattern (or donut-like ring pattern). In this process, connexin41.8 (or its mutant form) was ectopically expressed using the mitfa promoter. Specifically, the leopard pattern was generated as predicted by Turing's model. Our results demonstrate that the pigment cells in animal skin have the potential and plasticity to establish various patterns and that the reaction-diffusion principle can predict skin patterns of animals. PMID- 22313792 TI - Desmopressin and oxybutynin in monosymptomatic nocturnal enuresis: a randomized, double-blind, placebo-controlled trial and an assessment of predictive factors. AB - OBJECTIVES: To assess the efficacy of desmopressin plus oxybutynin and compare two starting dosages of desmopressin (120 and 240 ug) in a randomized, double blinded, placebo-controlled trial for children with monosymptomatic nocturnal enuresis (MNE) resistant to desmopressin. The predictive factors of children with MNE responsive to desmopressin and combination therapy were also evaluated. PATIENTS AND METHODS: Our sample included 206 patients aged between 6 and 13 (mean age 10.6 +/- 2.9 years), 117 males. All patients were required to have MNE. The patients were randomly divided into two groups: the first group was given oral melt 120 ug and the second group 240 ug, for 2 weeks. All patients who had experienced failure of treatment with sublingually administered desmopressin alone were given either desmopressin plus 5 mg oxybutynin or desmopressin plus placebo in a randomized, double-blinded trial for 4 weeks. As predictive factors, bladder volume and wall thickness index, nocturnal polyuria and voiding latency were considered. RESULTS: There was no significant difference between the 120 ug and 240 ug patients in terms of response. The oxybutynin group showed a higher rate of full and partial responses (45% success) compared with the placebo group (17% success), P < 0.01. The responders to combined oxybutynin and desmopressin had significantly lower bladder volume and wall thickness index than the other patients. CONCLUSIONS: Our findings highlight that anticholinergic agents may play an important role for a subset of children with enuresis who have a restricted bladder capacity and thickened bladder wall. Ultrasonography-measured bladder variables can provide useful predictive clues for MNE. Predictive factors can help to differentiate treatment subtypes and guide clinical management in primary nocturnal enuresis. PMID- 22313793 TI - Blood pressure decrease with ingestion of a soya product (kinako) or fish oil in women with the metabolic syndrome: role of adiponectin and nitric oxide. AB - The aim of the present study was to verify the effects of fish oil and a soya based product on inflammatory markers and endothelial function measured by NO in women with the metabolic syndrome (MetS). A total of sixty-five women (mean age: 47.9 (SD 9.98) years) were studied in a 90-d parallel, randomised design. A control group maintained their usual diet; the second group received 29 g/d of soyabean (kinako); the third group received 3 g/d of fish oil n-3 fatty acids; and the fourth group received fish oil (3 g/d) and kinako (29 g/d). Anthropometric, blood pressure (BP), inflammatory markers, anti-inflammatory marker (adiponectin) and NO concentrations were evaluated. In relation to the baseline values, the group that received fish oil and kinako concomitantly presented a statistically significant decrease in systolic BP (SBP; P < 0.05), whereas there was a significant decrease in diastolic BP (DBP) in the control group (P < 0.05), kinako group (P < 0.01) and fish oil group (P < 0.01) after 90 d. There was a significant increase in adiponectin (P < 0.01) and NO values (P < 0.05) after 90 d in the kinako and fish oil groups. Differences between treatment groups verified a significant decrease (P < 0.05) in DBP in the kinako group after 90 d when compared to the results obtained from the fish oil and kinako groups. In conclusion, the findings of increased serum adiponectin and NO metabolite levels after 90 d, both in the fish oil and soya groups, reinforce the importance of the influence of adiponectin and NO levels on BP decrease in patients with the MetS. PMID- 22313794 TI - Regeneration of uterine cervix at 6 months after large loop excision of the transformation zone for cervical intraepithelial neoplasia. AB - OBJECTIVE: To sonographically investigate cervical regeneration 6 months after large loop excision of the transformation zone (LLETZ) conisation for cervical intraepithelial neoplasia (CIN) pathology. DESIGN: Prospective observational study. SETTING: University Hospital setting. POPULATION: Women having LLETZ conisation for intraepithelial lesions in response to abnormal Papanicolaou smears or colposcopic findings. METHODS: Cervical dimensions were estimated before conisation and at 6 months with three-dimensional sonography and use of vocalTM software. Cone depth was measured using a ruler before fixation, and cone volume was measured using a volumetric tube and the fluid displacement technique. Cervical regeneration was sonographically estimated. MAIN OUTCOME MEASURES: Correlation of cervical volume regeneration with percentage of initial cervical volume excised and remaining cervical tissue immediately after conisation. RESULTS: A cohort of 112 women were initially recruited over a 2-year period and 73 women presented for ultrasound follow up at 6 months. Multivariate linear regression analysis showed that for women matched for age and initial cervical volume, if cervical volume excised was increased by 1% then regeneration of tissue deficit at the cervical crater was reduced by 1.37%. There also seemed to be a cutoff point suggesting that when >14% of initial cervical volume was excised, the tissue deficit at the cervical crater at 6 months was restored by <75% and there was >25% of remaining tissue deficit. CONCLUSIONS: Cervical regeneration at 6 months after excision is dependent on the percentage of initial cervical volume excised and on the remaining cervical tissue immediately after conisation. The greater the cone and the less cervical tissue remaining, the less the degree of cervical regeneration achieved. PMID- 22313795 TI - Increased serum sTRAIL levels were correlated with survival in bevacizumab treated metastatic colon cancer. AB - BACKGROUND: Colorectal cancer is the third most common cancer and the third leading cause of cancer-related death. Bevacizumab is a humanized monoclonal antibody developed against vascular endothelial growth factor (VEGF) for the treatment of metastatic cancer. The parameters of RECIST (Response Evaluation Criteria for Solid Tumors) are not adequate to detect important treatment effects and response. Our goal was to evaluate the possibility of using sTRAIL (serum soluble TNF-related apoptosis-inducing ligand) and VEGF as markers of treatment efficacy and prognosis in patients with metastatic colon cancer. METHODS: sTRAIL and VEGF levels were measured by ELISA in the sera of 16 bevacizumab-treated metastatic colon cancer patients and 10 presumably healthy age-matched controls. The measurements were taken before and after treatment for comparison purposes. RESULTS: Elevated levels of sTRAIL were found in seven out of 16 patients after bevacizumab treatment. Although these patients had a median survival time of 20.6 months, the remaining bevacizumab-treated patients who did not show an increase in sTRAIL had a median survival time of 9.4 months. As expected, serum VEGF levels were decreased in all patients who received bevacizumab therapy and showed no correlation between serum VEGF levels and patient survival (data not shown). CONCLUSIONS: Serum sTRAIL levels might be a useful predictor of prognosis in metastatic colon cancer, in the early evaluation stages following bevacizumab treatment. PMID- 22313796 TI - Biologic and epigenetic impact of commuting to work by car or using public transportation: a case-control study. AB - BACKGROUND AND AIMS: Commuting by public transportation (PT) entails more physical activity and energy expenditure than by cars, but its biologic consequences are unknown. METHODS: In 2009-2010, we randomly sampled New York adults, usually commuting either by car (n=79) or PT (n=101). Measures comprised diet and physical activity questionnaires, weight and height, white blood cell (WBC) count, C reactive protein, (CRP) gene-specific methylation (IL-6), and global genomic DNA methylation (LINE-1 methylation). RESULTS: Compared to the 101 PT commuters, the 79 car drivers were about 9 years older, 2 kg/m(2) heavier, more often non-Hispanic whites, and ate more fruits and more meats. The 2005 guidelines for physical activity were met by more car drivers than PT users (78.5% vs. 65.0%). There were no differences in median levels of CRP (car vs. PT: 0.6 vs. 0.5mg/dl), mean levels of WBC (car vs. PT: 6.7 vs. 6.5 cells/mm(3)), LINE 1 methylation (car vs. PT: 78.0% vs. 78.3%), and promoter methylation of IL-6 (car vs. PT: 56.1% vs. 58.0%). CONCLUSIONS: PT users were younger and lighter than car drivers, but their commute mode did not translate into a lower inflammatory response or a higher DNA methylation, maybe because, overall, car drivers were more physically active. PMID- 22313797 TI - Poor sleep at baseline predicts worse mood outcomes in patients with co-occurring bipolar disorder and substance dependence. AB - BACKGROUND: Sleep problems are common in patients with bipolar disorder and have been shown to predict subsequent mood symptoms. Sleep problems have also been shown to lead to worse substance use outcomes in individuals with substance use disorder. However, the relationship between sleep and clinical outcomes in a population with co-occurring bipolar disorder and substance use disorder is unclear. METHOD: This secondary analysis included 60 outpatients (mean age = 38.1 years; recruited via advertisements, fliers, clinician referrals, and hospital treatment programs) who met DSM-IV criteria for both bipolar disorder and substance use disorder (assessed with the Structured Clinical Interview for DSM IV Axis I Disorders) and who participated in a randomized clinical trial comparing integrated group therapy for bipolar disorder and substance use disorder to group drug counseling for substance use disorder alone. A 12-week treatment period preceded a 24-week follow-up. Poor sleep was assessed with the Pittsburgh Sleep Quality Index, which provides 7 component subscores and an overall sleep score. Data were collected from August 2003 through April 2007. RESULTS: When analyses were controlled for baseline mood, substance use, and treatment condition, baseline sleep score predicted mood over the course of the 12-week treatment (beta = 0.28; P < .05) and 24-week follow-up (beta = 0.46; P < .01): worse sleep was associated with worse mood outcomes. Sleep was not associated with substance use outcomes. CONCLUSIONS: Impaired sleep is a prognostic factor for mood outcomes in patients with co-occurring bipolar and substance use disorders. Further investigation is warranted into the long-term clinical outcomes of poor sleep in this population with co-occurring bipolar disorder and substance use disorder so that appropriate interventions can be developed. PMID- 22313798 TI - Risk factors for sporadic Yersinia enterocolitica infections, Germany 2009-2010. AB - Yersinia enterocolitica is an important cause of acute gastrointestinal disease and post-infectious complications. In Germany, incidence of reported yersiniosis is relatively high compared with other countries of the European Union. Children aged <5 years are most frequently affected. The aim of our study was to identify risk factors for sporadic yersiniosis in Germany. A population-based case-control study was conducted in five federal states of Germany from April 2009 to June 2010. Cases exhibiting gastrointestinal symptoms were notified to the local health department with a Yersinia enterocolitica infection culture-confirmed from stool. Controls were selected from population registries and frequency-matched on age group and state of residency. Cases and controls received a questionnaire on possible risk factors by mail. Multivariable logistic regression modelling was used to identify risk factors and to calculate adjusted odds ratios (aORs). Population attributable fractions (PAFs) were estimated for exposures associated with yersiniosis. We analysed data on 571 case patients and 1798 controls. Consumption of raw minced pork, a dish frequently consumed even by young children in Germany, was the main risk factor for disease (aOR 4.7, 95% confidence interval (CI) 3.5-6.3, PAF 30%). This association varied by age group and, unexpectedly, was strongest for children aged <2 years (aOR 17.5, 95% CI 6.0 51.2). Other independent risk factors included recent preparation of minced pork in the household (aOR 1.4, 95% CI 1.1-1.9, PAF 21%), playing in a sandbox (aOR 1.7, 95% CI 1.3-2.4, PAF 17%), and contact with birds (aOR 1.7, 95% CI 1.1-2.6, PAF 4%). Prevention efforts should specifically target parents and caregivers of young children and focus on the high infection risk associated with consumption of raw minced pork. PMID- 22313799 TI - Insertion site preference of Mu, Tn5, and Tn7 transposons. AB - BACKGROUND: Transposons, segments of DNA that can mobilize to other locations in a genome, are often used for insertion mutagenesis or to generate priming sites for sequencing of large DNA molecules. For both of these uses, a transposon with minimal insertion bias is desired to allow complete coverage with minimal oversampling. FINDINGS: Three transposons, Mu, Tn5, and Tn7, were used to generate insertions in the same set of fosmids containing Candida glabrata genomic DNA. Tn7 demonstrates markedly less insertion bias than either Mu or Tn5, with both Mu and Tn5 biased toward sequences containing guanosine (G) and cytidine (C). This preference of Mu and Tn5 yields less uniform spacing of insertions than for Tn7, in the adenosine (A) and thymidine (T) rich genome of C. glabrata (39% GC). CONCLUSIONS: In light of its more uniform distribution of insertions, Tn7 should be considered for applications in which insertion bias is deleterious. PMID- 22313800 TI - Prognostic value of venous blood ammonia in patients with out-of-hospital cardiac arrest. AB - BACKGROUND: Although studies have shown there is a correlation between increased blood ammonia level and hepatic encephalopathy, little information is available for patients with out-of-hospital cardiac arrest. METHODS AND RESULTS: We did a prospective study of 357 adult patients with out-of-hospital cardiac arrest whose venous blood ammonia levels were measured on arrival at the emergency room. The primary endpoint was favorable of neurological outcome to hospital discharge. Of the 357 patients, 25 (7%) had a favorable neurological outcome. The venous ammonia levels were lower in the favorable neurological outcome group than in the unfavorable neurological outcome group (median, 50 ug/dl vs. 210 ug/dl, P<0.0001). The adjusted odds ratio of ammonia levels for favorable neurological outcome was 0.98 (95% confidence interval, 0.96-0.99; P<0.0001). The ammonia cutoff value of 93.0 ug/dl for the identification of favorable neurological outcome had the highest combined sensitivity and specificity, and higher ammonia levels were associated with more accurate negative predictive values (for ammonia levels of 192.5 ug/dl, the negative predictive value was 100%). Hyperammonemia was significantly related to patient variables that had a poor outcome (R=0.439, P<0.001). In addition, there was a significant correlation between venous ammonia level and arterial pH on emergency room arrival (R=0.633, P<0.0001). CONCLUSIONS: The measurement of ammonia was found to provide valuable information regarding neurological outcome to hospital discharge in adult patients with out-of-hospital cardiac arrest. PMID- 22313801 TI - Inhibition of protein kinase C beta ameliorates impaired angiogenesis in type I diabetic mice complicating myocardial infarction. AB - BACKGROUND: In recent studies, the inhibition of protein kinase C (PKC) beta has been shown to improve diabetic vascular complications. However, the effect on angiogenesis in myocardial ischemia with diabetes mellitus (DM) is still unknown. METHODS AND RESULTS: Mice were divided into 3 groups: control, DM and DM+PKC-I groups (n=8, respectively). In the DM and DM+PKC-I groups, diabetes was induced by streptozotocin (STZ) (1.5mg/body i.p.) for 5 days. Next, left anterior descending artery (LAD) ligation was performed in all groups. In the DM+PKC-I group, PKC beta inhibitor (Cat. No. 539654; 10 nmol/L) was administered from days 1 to 10. After 4 weeks of LAD ligation, the animals were killed. Microvascular density was significantly improved by PKC beta inhibitor (control: 87.9+/ 5.2/high-power field (HPF); DM: 51.4+/-6.9/HPF; PKC-I: 80.3+/-4.9/HPF; P<0.05). Expression of both vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS), which was decreased in the DM group, were significantly improved by inhibition of PKC beta [VEGF (DM: 0.36+/-0.11-fold and DM+PKC-I: 0.77+/-0.07-fold vs. control), eNOS (DM: 0.35+/-0.06-fold and DM+PKC-I: 0.73+/-0.08-fold vs. control); both P<0.05)]. CONCLUSIONS: Inhibition of PKC beta ameliorated impaired angiogenesis by hyperglycemia in STZ-induced DM mice complicated by myocardial infarction. These results suggest a new possible indication of PKC beta inhibitor for myocardial ischemia with DM. PMID- 22313802 TI - A half-century of autopsy results--incidence of pediatric vasculitis syndromes, especially Kawasaki disease. AB - BACKGROUND: The objectives of this study were to clarify the details of pediatric vasculitic diseases on the basis of Japanese autopsy reports and determine whether there were cases of probable Kawasaki disease (KD) even before KD came to be widely recognized as a disease entity. METHODS AND RESULTS: Systemic vasculitis autopsy cases aged 15 years or less were selected from the total of 1,335,045 autopsy cases listed in the Annual of Pathological Autopsy Cases in Japan from 1958 through 2008. Those cases were classified into 14 disease groups and then analyzed with regard to various details. There were 380 autopsy cases of vasculitis in children (0.03% of the total autopsy cases). More than half were KD, and other diseases included unclassified vasculitis, polyarteritis nodosa, purpuric vasculitis, Takayasu arteritis, etc. The first recorded case of KD autopsy occurred in 1969. Up until 1976 there was a great difference in the number of autopsies between pediatric vasculitis and KD. However, after 1977 their numbers were in close agreement. The autopsy findings for 24 of 125 child vasculitis autopsies performed before 1976 and diagnosed as non-KD were consistent with KD. CONCLUSIONS: Although autopsies of pediatric vasculitis cases are extremely rare, the majority consists of KD. Moreover, it is likely that autopsy cases that were probably KD first appeared in the early 1960s. PMID- 22313803 TI - Equilibrium radionuclide angiography for evaluating the effect of facilitated percutaneous coronary intervention on ventricular synchrony in patients with acute myocardial infarction. AB - BACKGROUND: It is unclear whether facilitated percutaneous coronary intervention (PCI) via a transradial approach therapy is preferable to primary PCI, with improved ventricular synchrony performance (VS), in Chinese patients. METHODS AND RESULTS: The 152 patients with their first anterior acute myocardial infarction (AMI) were randomized to a primary PCI group or facilitated PCI group. In the 1(st) week and 6(th) month after AMI onset, the parameters of VS were measured by equilibrium radionuclide angiography with ventricular phase analysis. The rate of TIMI grade-3 flow in the infarct-related artery pre-PCI in the facilitated PCI group was higher than that in the primary PCI group (30.56% vs. 8.45%, P=0.001). At the 6(th) month post-AMI, the parameters of time to peak ejection rate, phase shift and peak phase standard deviation were lower than in the primary PCI group (P<0.05, respectively). The incidence of recurrent ischemia and new or worsening congestive heart failure post-AMI in the facilitated PCI group was significantly lower than that in the primary PCI group (2.78% vs. 9.86%, P=0.043; 2.78% vs. 12.68%, P=0.028). CONCLUSIONS: Facilitated PCI via a transradial approach might significantly inhibit left ventricular remodeling and improve left ventricular function because of the complete, persistent patency of the infarct-related artery with few complications of vessel access and bleeding. PMID- 22313804 TI - Clinical significance of reactive post-capillary pulmonary hypertension in patients with left heart disease. AB - BACKGROUND: Post-capillary pulmonary hypertension (pc-PH) is a disorder with elevated pulmonary arterial pressure and pulmonary vascular resistance (PVR) because of left heart disease (LHD), and is classified as reactive (PVR >2.5 WU) or passive (PVR <= 2.5 WU). However, the clinical significance of these pc-PH subtypes remains to be elucidated. METHODS AND RESULTS: We examined 676 consecutive patients with chronic heart failure (CHF) (NYHA >= 2), and found that 158 (23%) had pc-PH: reactive pc-PH in 58 and passive pc-PH in 100. Univariate analysis showed that 4 factors were significantly associated with reactive pc-PH and multivariate analysis showed that female sex was the only independent predictor of reactive pc-PH (odds ratio 2.12, 95% confidence interval (CI) 1.05 4.30, P=0.03). During the mean follow-up period of 2.6 years, 125 CHF patients (18%) died, including 22 with reactive pc-PH and 24 with passive pc-PH (P<0.001). Multivariate Cox regression analysis showed that elevated PVR was independently associated with higher mortality (hazard ratio 1.18, 95%CI 1.03-1.35, P=0.02). Kaplan-Meier analysis demonstrated that the prognosis of patients with reactive pc-PH was significantly worse than for those with no PH or passive pc-PH. Reactive pc-PH was a significant prognostic factor regardless of CHF etiology (ischemic vs. non-ischemic) or reduced/preserved LV ejection fraction (HFrEF vs. HFpEF). CONCLUSIONS: Reactive pc-PH is characterized by predominant female sex and is a significant prognostic factor of LHD with PH. PMID- 22313805 TI - The Taiwan Society of Cardiology. PMID- 22313806 TI - Positive and negative selection towards tetracycline resistance genes in manure treatment lagoons. AB - AIMS: To evaluate the role of manure treatment lagoons of swine operations in the fate of faeces- and feed-borne tetracycline-resistant genes (TRG). METHODS AND RESULTS: Samples of feed, faeces, lagoon liquid and lagoon sediment in farm's vicinity were collected at three swine operations varied on their operational practices and analysed on the presence and frequencies of incidence of sixteen TRG in upstream sources (feed, faeces) and downstream receptacles (lagoon liquid and sediments). The highest frequency of TRG incidence was observed in a farm with extensive antibiotic usage and the lowest in the antibiotic-free farm. The study revealed a decrease in TRG richness and diversity in the downstream habitats of each farm. The observed TRG diverged into two groups, the persistent genes that were detected both upstream and downstream, and the transient genes that were detected in the upstream habitats but became nondetectable in the lagoons. Quantitative PCR analysis revealed that upstream concentrations and abundances (determined as TRG/16S rRNA gene ratios) of transient and persistent TRG were similar; however, the former were attenuated in the lagoons to the levels below the detection limit, whereas the latter were ~ 100-1000 fold amplified in their (mostly) liquid phases and were also detected in farms' vicinities. CONCLUSION: Manure lagoons of swine operations imposed both positive and negative selection towards faeces- and feed-borne TRG that, respectively, caused either their proliferation or attenuation in those environments. SIGNIFICANCE AND IMPACT OF THE STUDY: The study reveals that discharge of antibiotic resistance genes from swine farms to the environment is linked to their positive selection (defined as an impact leading to proliferation of those genes) in manure lagoons. PMID- 22313807 TI - Doped carbon nanotube networks for electrochemical filtration of aqueous phenol: electrolyte precipitation and phenol polymerization. AB - Electrochemical filtration with anodic carbon nanotube (CNT) networks is reported to be effective for chemical and microbiological water treatment. Here, we investigate how CNT doping affects the electrochemical filtration performance toward the remediation of aromatic wastewaters. Purified and well-characterized undoped (C-CNT), boron-doped (B-CNT), and nitrogen-doped (N-CNT) anodic carbon nanotube networks are challenged with aqueous phenol in a sodium sulfate electrolyte. Steady-state current and effluent total organic carbon (TOC) measurements are utilized to evaluate the oxidative performance as a function of voltage and electrolysis time. In terms of steady-state TOC removal, at an applied voltage of 3 V all three anodic CNT networks are able to remove approximately 7 to 8 mgC L(-1) of the influent TOC within the ~1 s liquid residence time of the electrochemical filter. The anodic CNT networks are partially passivated over the 5 h electrolysis time with the B-CNT network displaying the least passivation. The extent of passivation was observed to be inversely correlated to the CNT work function. SEM, XPS, and TGA of the electrolyzed CNT networks are used to identify the two primary passivation mechanisms of electrochemical phenols polymerization and electrochemical electrolyte precipitation. In agreement with chronoamperometry results, the B-CNT network has the lowest extent of passivating polymer and precipitate formation. The precipitant is determined to likely be sodium persulfate or carbonate and is removed with a simple acidic water wash. The polymer is determined to likely be polyphenylene oxide and is partially removed with the wash. All three anodic CNT networks display potential for energy efficient electrochemical filtration of aromatic wastewaters and the B-CNT are determined to be the most resistant to passivation. PMID- 22313808 TI - The value of extended transurethral resection of bladder tumour (TURBT) in the treatment of bladder cancer. PMID- 22313809 TI - Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men. AB - Feeding stimulates robust increases in muscle protein synthesis (MPS); however, ageing may alter the anabolic response to protein ingestion and the subsequent aminoacidaemia. With this as background, we aimed to determine in the present study the dose-response of MPS with the ingestion of isolated whey protein, with and without prior resistance exercise, in the elderly. For the purpose of this study, thirty-seven elderly men (age 71 (sd 4) years) completed a bout of unilateral leg-based resistance exercise before ingesting 0, 10, 20 or 40 g of whey protein isolate (W0-W40, respectively). Infusion of l-[1-13C]leucine and l [ring-13C6]phenylalanine with bilateral vastus lateralis muscle biopsies were used to ascertain whole-body leucine oxidation and 4 h post-protein consumption of MPS in the fed-state of non-exercised and exercised leg muscles. It was determined that whole-body leucine oxidation increased in a stepwise, dose dependent manner. MPS increased above basal, fasting values by approximately 65 and 90 % for W20 and W40, respectively (P < 0.05), but not with lower doses of whey. While resistance exercise was generally effective at stimulating MPS, W20 and W40 ingestion post-exercise increased MPS above W0 and W10 exercised values (P < 0.05) and W40 was greater than W20 (P < 0.05). Based on the study, the following conclusions were drawn. At rest, the optimal whey protein dose for non frail older adults to consume, to increase myofibrillar MPS above fasting rates, was 20 g. Resistance exercise increases MPS in the elderly at all protein doses, but to a greater extent with 40 g of whey ingestion. These data suggest that, in contrast to younger adults, in whom post-exercise rates of MPS are saturated with 20 g of protein, exercised muscles of older adults respond to higher protein doses. PMID- 22313810 TI - A multicentre prospective study of post-traumatic endophthalmitis. AB - PURPOSE: Study the clinical and microbiological characteristics and the prognostic factors of post-traumatic endophthalmitis. METHODS: Seventeen eyes were included between 2004 and 2010, with clinical and microbiological data collected prospectively. Conventional cultures and panbacterial PCR were performed on aqueous and vitreous samples. RESULTS: Clinical signs of endophthalmitis were observed soon after trauma (1.5 +/- 2.5 days). Laceration with an intraocular foreign body (IOFB) was noted in 53% of the patients. At admission, all patients had aqueous humour (71%) and/or vitreous (53%) samples. Fifteen patients (88%) underwent a pars plana vitrectomy. Bacteria were identified in 77% of the cases: Staphylococcus epidermidis (n = 5), Streptococcus (n = 4), Bacillus (n = 2), Pseudomonas stuzeri (n = 1), and Streptococcus salivarius and Gemella haemolysans (multibacterial infection, n = 1). Progression toward phthisis was observed in 35% of the cases; 41% of the patients recuperated visual acuity (VA) >=20/40. A good final visual prognosis (>=20/40) was significantly associated with initial VA better than light perception (0% versus 70%, p = 0.01) and absence of pupillary fibrin membrane (80% versus 20%, p = 0.05). There was no correlation between visual prognosis and age, the type of laceration (corneal or scleral) or presence of an IOFB. We found a statistical trend toward an association between bacterial virulence and poor final VA. CONCLUSION: This series showed that better final VA outcomes were associated with initial VA better than light perception, S. epidermidis or culture-negative cases and absence of retinal detachment during the clinical course. PMID- 22313812 TI - Electrical characterization and nanoscale surface morphology of optimized Ti/Al/Ta/Au ohmic contact for AlGaN/GaN HEMT. AB - Good ohmic contacts with low contact resistance, smooth surface morphology, and a well-defined edge profile are essential to ensure optimal device performances for the AlGaN/GaN high electron mobility transistors [HEMTs]. A tantalum [Ta] metal layer and an SiNx thin film were used for the first time as an effective diffusion barrier and encapsulation layer in the standard Ti/Al/metal/Au ohmic metallization scheme in order to obtain high quality ohmic contacts with a focus on the thickness of Ta and SiNx. It is found that the Ta thickness is the dominant factor affecting the contact resistance, while the SiNx thickness affects the surface morphology significantly. An optimized Ti/Al/Ta/Au ohmic contact including a 40-nm thick Ta barrier layer and a 50-nm thick SiNx encapsulation layer is preferred when compared with the other conventional ohmic contact stacks as it produces a low contact resistance of around 7.27 * 10-7 Omega.cm2 and an ultra-low nanoscale surface morphology with a root mean square deviation of around 10 nm. Results from the proposed study play an important role in obtaining excellent ohmic contact formation in the fabrication of AlGaN/GaN HEMTs. PMID- 22313811 TI - Intrinsic and extrinsic modifiers of the regulative capacity of the developing liver. AB - Zebrafish wnt2bb mutants initially fail to form a liver, but surprisingly the liver eventually forms in a majority of these embryos which then develop into fertile adults. This unexpected result raised the possibility that identifying the mechanisms of liver formation in wnt2bb mutants could provide insights into the poorly understood yet general principle of regulative development, a process by which some cells can change fate in order to compensate for a deficiency. Here, we identify two factors that underlie the regulative capacity of endodermal tissues: an intrinsic factor, Sox32, a transcription factor of the SoxF subfamily, and an extrinsic factor, Fgf10a. sox32 is expressed in the extrahepatic duct primordium which is not affected in wnt2bb mutants. Blocking Sox32 function prevented liver formation in most wnt2bb mutants. fgf10a, which is expressed in the mesenchyme surrounding non-hepatic endodermal cells, negatively impacts the regulative capacity of endodermal tissues. In Wnt/beta-catenin signaling deficient embryos, in which the liver completely fails to form, the repression of Fgf10a function allowed liver formation. Altogether, these studies reveal that there is more than one way to form a liver, and provide molecular insights into the phenomenon of tissue plasticity. PMID- 22313813 TI - Impact of deleting 5 DSM-IV personality disorders on prevalence, comorbidity, and the association between personality disorder pathology and psychosocial morbidity. AB - OBJECTIVE: A high rate of comorbidity among the personality disorders has been consistently identified as a problem. To address the problem of excessive comorbidity, the DSM-5 Personality and Personality Disorders Work Group recommended reducing the number of specific personality disorder diagnoses from 10 to 5 by eliminating paranoid, schizoid, histrionic, narcissistic, and dependent personality disorders. No study has examined the impact of this change. The present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project examined the impact of eliminating these 5 personality disorders on the prevalence of personality disorders in a large sample of psychiatric outpatients presenting for treatment, comorbidity among the personality disorders, and association with psychosocial morbidity. METHOD: From September 1997 to June 2008, 2,150 psychiatric patients presenting to the Rhode Island Hospital outpatient practice were evaluated with semistructured diagnostic interviews for DSM-IV Axis I and Axis II disorders and measures of psychosocial morbidity. RESULTS: More than one-quarter of the patients were diagnosed with one of the 10 DSM-IV personality disorders (28.6%, n = 614). When 5 personality disorders were excluded from consideration, then 25.8% (n = 555) were diagnosed with at least 1 of the 5 personality disorders proposed for retention in DSM-5, and the comorbidity rate dropped from 29.8% to 21.3%. Compared to patients without a personality disorder, the patients with either a retained or an excluded personality disorder had greater psychosocial morbidity. There was little difference in psychosocial morbidity between patients with a retained and an excluded personality disorder. CONCLUSIONS: The Personality and Personality Disorders Work Group's desired goal of reducing comorbidity would be achieved by deleting 5 personality disorders, although comorbidity would not be eliminated. The reduction of comorbidity could come with a cost of false-negative diagnoses. The results therefore do not provide unambiguous support for the DSM-5 proposed elimination of 5 personality disorders. PMID- 22313814 TI - Making the most of our gifts. PMID- 22313815 TI - Zoledronic acid and osteonecrosis of the jaw: incidence varies with use. PMID- 22313816 TI - Impression making with gingival hyperplasia using the copper band technique. PMID- 22313817 TI - Fixed-detachable implant restoration of the edentulous maxilla. PMID- 22313818 TI - Comparison of flexural properties and surface roughness of nanohybrid and microhybrid dental composites. AB - Recently introduced nanohybrid dental composites have promised a smoother surface finish and strength, comparable to that of microhybrid composites. This study compared the mechanical properties and surface finish of nanohybrid and microhybrid composites by measuring the flexural strength and modulus (four-point bend) and surface roughness after polishing (using atomic force microscopy) of six commercial dental composites (three nanohybrid, three microhybrid). Scanning electron microscopy (SEM) was used to qualitatively characterize filler morphology and size. The flexural strength and modulus were significantly higher among the microhybrid composites, while the nanohybrid composites exhibited significantly lower surface roughness. SEM characterization revealed differences in filler particle size and shape that could affect the flexural properties and surface roughness. Composites containing spherical filler particles exhibited higher flexural properties and lower roughness values compared to composites with irregular fillers. These results did not support the premise that nanohybrid composites offer similar mechanical properties to microhybrids in addition to a better surface finish. PMID- 22313819 TI - A quadrant tray and bite registration as an alternative to dual-arch impressions for fixed prosthetics: a clinical and dental laboratory technique. AB - To perform fixed prosthodontic procedures, dentists take a full-arch or quadrant impression and articulate the casts. The dual-arch impression technique is a popular quadrant technique for crown fabrication. The technique described in this article, which uses a quadrant impression and separate interocclusal record, offers several advantages over the traditional dual-arch method. PMID- 22313820 TI - Impact of drug abuse/dependence on dentists. AB - Drug abuse and dependence are important and complex health problems, and understanding these issues is important for dental patient management. At the same time, dentists, like their patients, could abuse alcohol and other illicit drugs, which would jeopardize their ability to provide optimum dental care. This article reviews important aspects of drug abuse and dependence, risk factors for dentists, the impact of drug abuse on the dental profession, and various treatment options. PMID- 22313821 TI - Crown lengthening with removable orthodontics: a combined approach for ideal esthetics. AB - Cases in which a single tooth is in need of crown lengthening while remaining esthetically pleasing represent a unique challenge. A case is presented here in which crown lengthening in a challenging esthetic situation on a canine was achieved through forced eruption with a removable orthodontic appliance. The case was considered a success by both the clinician and the patient. Fabrication of the acrylic stent is a simple procedure that can be completed chairside, and the patient's acceptance of the appliance as well as the overall cost and time invested made this a very convenient alternative. The report emphasizes the general dentist's complete control over each treatment sequence. PMID- 22313822 TI - The systemic theory of dental caries. AB - There is growing awareness of oral/systemic links, especially with regard to periodontal disease, diabetes, and cardiovascular disease, among others. The process of dental caries has similar links. Bacterial and other acids in the oral environment can erode enamel and potentially initiate an inflammatory response in the dentin. The body's own matrix metalloproteinases, mostly from within the dentin, become activated, resulting in the caries process. A simplified explanation of the oxidative stress causing inflammation is developed from three equations, namely Health, Disease, and Disease. The healthy tooth is nourished by a centrifugal dentinal fluid flow. This flow is controlled by signals from the hypothalamus that are relayed to the endocrine portion of the parotid gland. The first step in the caries process is the reversal of the dentinal fluid flow, rather than the acid attack from the oral environment. A systemic understanding of the actual cause and progression of dental caries creates opportunities for more effective approaches to preventive care. PMID- 22313823 TI - The influence of obturation technique on sealer thickness and depth of sealer penetration into dentinal tubules evaluated by computer-aided digital analysis. AB - The aim of this study was to determine sealer penetration into dentinal tubules and sealer thickness with different obturation materials and techniques, with the null hypothesis that sealer cement thickness and dentinal tubule penetration was not affected by obturation technique. This study used 180 freshly extracted human mandibular premolars. Samples were obturated using the lateral condensation technique with either gutta-percha (Group 1) or Resilon (Group 2), using AH Plus (subgroup A) or Epiphany (subgroup B) as a sealer. Other samples were obturated with One-Step Obturator (Group 3) using AH Plus or Epiphany sealer. The sealer thickness and sealer penetration into dentinal tubules was evaluated using stereomicroscopy and analysis of digital images using AutoCAD software at 5.0 mm, 3.0 mm, and 1.0 mm from the apex. The mean value of sealer thickness for Group 3 was significantly lower than the mean values of the other groups. There was no significant difference in the mean values between subgroups A and B for Group 1 or Group 3, whereas for Group 2, the mean value in subgroup A was significantly higher than the mean value in subgroup B. The greatest average frequency of the penetration of sealer cement was found at the 5.0 mm level, followed by the 3.0 mm level, which, in turn, was greater than at the 1.0 mm level. The thickness of the sealer cement is dependent on the obturation technique employed, while the penetration of the sealer into the dentinal tubules is independent of the obturation technique. PMID- 22313824 TI - Gingival esthetic outcome around a bone-level implant--a case report. AB - The objective of this case report is to review the clinical thinking, decision making, and actions of the authors, from the time of the first patient visit to the final esthetic outcome. Initial uncertainty led the authors to perform procedures that were believed to provide best outcomes or alternatives for further procedures, if necessary. An optimal final esthetic outcome was the goal, and the short-term (one-year) esthetic results are presented. PMID- 22313825 TI - Color stability of composite resin cements. AB - This study sought to determine the difference in color stability of resin cements after one year of storage in water. Three commercial resin cements (Nexus 3, Calibra, Variolink 2) were evaluated under three different curing conditions (photo-, dual-, and self-cure) over three storage time periods (3, 6, and 12 months). A plastic mold was used to prepare cylindrical specimens of each of the three resin cements. For the phototcured specimens, only the base component of the resin cement was cured. For the dual- and self-cure specimens, the base and catalyst of the cements were mixed according to the manufacturer's instructions, syringed into the mold, and either photocured as before (dual-cure) or allowed to chemically set (self-cure). The total amount of color change (delta E) was calculated using a spectrophotometer after 24 hours (baseline) and after 3, 6, and 12 months of storage in distilled water. Data were analyzed using a repeated measures ANOVA and a Tukey test. After one year of storage, Nexus 3 demonstated the lowest color change values (delta E) under all curing conditions, although it was not significantly different from Variolink 2 when photocured or Calibra when self-cured. New resin cements without a traditional benzoyl peroxide/amine redox initiator system, such as Nexus 3, could be more color-stable over time. PMID- 22313826 TI - Interradicular radiolucency. Lateral periodontal cyst. PMID- 22313827 TI - Bilateral buccal swellings. Buccal bifurcation cyst. PMID- 22313828 TI - Multi-step adhesive cementation versus one-step adhesive cementation: push-out bond strength between fiber post and root dentin before and after mechanical cycling. AB - This study evaluated the effects of mechanical cycling on resin push-out bond strength to root dentin, using two strategies for fiber post cementation. Forty bovine roots were embedded in acrylic resin after root canal preparation using a custom drill of the fiber post system. The fiber posts were cemented into root canals using two different strategies (N = 20): a conventional adhesive approach using a three-step etch-and-rinse adhesive system combined with a conventional resin cement (ScotchBond Multi Purpose Plus + RelyX ARC ), or a simplified adhesive approach using a self-adhesive resin cement (RelyX U100). The core was built up with composite resin and half of the specimens from each cementation strategy were submitted to mechanical cycling (45 degree angle; 37 degrees C; 88 N; 4 Hz; 700,000 cycles). Each specimen was cross-sectioned and the disk specimens were pushed-out. The means from every group (n = 10) were statistically analyzed using a two-way ANOVA and a Tukey test (P = 0.05). The cementation strategy affected the push-out results (P < 0.001), while mechanical cycling did not (P = 0.3716). The simplified approach (a self-adhesive resin cement) had better bond performance despite the conditioning. The self-adhesive resin cement appears to be a good option for post cementation. Further trials are needed to confirm these results. PMID- 22313829 TI - Reattachment of fractured fragment of an anterior tooth: case report and nine year follow-up. AB - This article reports the treatment and follow-up of a 10-year-old boy who had a politraumatic accident that resulted in severe displacement and fracture of the maxillary right central incisor. After clinical and radiographic examination, the tooth fragment was bonded with adhesive and the tooth crown underwent nonrigid splinting. Follow-up appointments were scheduled once a week during the first month, once during the second month, and every three months thereafter. Each follow-up appointment included a clinical examination, followed by radiographic and pulp sensitivity tests. After the fifth year, pulp necrosis was diagnosed following a sensitivity test and a periapical radiograph. Endodontic treatment was performed; the chemical-mechanical preparation and root canal fillings used calcium hydroxide paste manipulated with saline solution. The abovementioned paste was replaced twice during the first month; after that, propylenoglycol was used as the vehicle for manipulating the calcium hydroxide. The filling paste was replaced whenever the radiographic image showed resorption of the paste. The root canals were filled definitively seven years postaccident. Nine years postaccident, clinical and radiographic examination revealed a normal aspect. PMID- 22313830 TI - Focal hypercementosis affecting a mandibular molar: a case report. AB - Hypercementosis is an abnormal thickening of the cementum. Although the etiology of this condition is uncertain, it occasionally is related to disorders of bone metabolism, including Paget disease and hyperthyroidism. The case presented here illustrates localized idiopathic deposition of excess cementum at the apex of the distal root of a mandibular first molar. PMID- 22313831 TI - Use of corticocancellous allogeneic bone blocks impregnated with bone marrow aspirate: a clinical, tomographic, and histomorphometric study. AB - The aim of this study was to evaluate the efficacy of allogeneic block grafts impregnated with autologous bone marrow in horizontal ridge augmentation therapy. Ten patients with severe ridge volume deficiency in the anterior maxilla were treated with horizontal ridge augmentation. The patients were randomized into two groups: Five patients, using two allogeneic block grafts, were in the control group, and five patients, using two allogeneic block grafts impregnated with autologous bone marrow, were in the test group. Hematologists collected 4 mL of bone marrow from the iliac crest of the patients in the test group immediately prior to the surgeries. The blocks were fixed using titanium screws to obtain rigid fixation and to standardize the reference points for measurement purposes. CT scans were obtained both preoperatively and six months postoperatively to allow evaluation of horizontal bone gain. After a healing period of six months, the sites were reopened and the screws were removed. Before implant placement, bone cores were harvested and prepared for histologic and histomorphometric evaluation. Tomographic and histomorphometric measurements were recorded. The test group demonstrated better tomographic results (P < 0.05) in augmenting alveolar thickness, with a mean value of 4.60 +/- 1.43 mm (118.23 +/- 56.93%), while the control group had bone gain of 2.15 +/- 0.47 mm (49.91 +/- 20.24%). Despite the different results in alveolar thickness gained between groups, all sites received dental implants. The histomorphometric analysis also showed better results (P < 0.05) in the amount of vital mineralized bone in the test group as compared to the control group. The findings of this study suggest that an autologous bone marrow aspirate can increase the regenerative potential of corticocancellous allogeneic bone grafts. PMID- 22313832 TI - The importance of oral-clinical findings for the correct diagnosis of Ellis-van Creveld syndrome. AB - Ellis-van Creveld syndrome (EVC), also known as chondroectodermal dysplasia, is a rare autosomal recessive disorder. It is characterized by a variable spectrum of clinical findings, and the most common tetrad is chondrodystrophy, polydactyly, ectodermal dysplasia, and cardiac defects. Among the oral findings, number anomalies, peg-shaped teeth, and alterations in soft tissues are noteworthy. The aim of this paper is to report a case in which the diagnosis of EVC was possible only with the oral findings of a dentist and to relate the dental treatment performed. A 2-year-old girl was brought for dental care due to a lack of teeth. Her condition was initially diagnosed as thanatophoric dysplasia by her pediatrician. After evaluation of the oral manifestations, the dentist referred her to a geneticist, with the suggestion of EVC. The dental report, together with the systemic manifestations, allowed the geneticist to confirm the EVC diagnosis. The necessary dental procedures were performed, and the patient, now age 5, is still monitored by a multidisciplinary team. PMID- 22313833 TI - Giant submandibular sialoliths: a report of two cases. AB - Sialolithiasis is the second most common disease of the salivary glands. Sialolithiasis accounts for the most common cause of salivary gland obstruction, leading to recurrent painful swelling of the involved gland, which often becomes worse while eating. Sialoliths can occur in any of the salivary glands but appear most frequently in the submandibular gland and its duct. Very few cases of giant submandibular sialoliths have been reported in the literature. This article reports two cases of unusually large submandibular sialoliths, with clinical and radiographical signs and management. The article also reviews the various diagnostic modalities and treatment options available. PMID- 22313834 TI - Fracture resistance of composite resin cores with or without prefabricated posts over different substrates. AB - The fracture resistance of endodontically treated teeth has been an obstacle to the durability of the remaining teeth and restorations. The aim of this study was to evaluate the fracture resistance of endodontically treated bovine and human teeth that were restored with either prefabricated metal posts, glass fiber posts, or composite resin cores. Statistical analysis revealed significant difference between different substrates, but there was no statistically significant difference between different types of intraradicular posts or in the interaction between substrate and post types. The intraradicular posts do not increase the fracture resistance of endodontically treated teeth. The metal posts presented more unfavorable fracture modes when compared to glass fiber posts and composite resin cores. PMID- 22313835 TI - Primary mediastinal "thymic" seminomas. AB - Over the last half century, our knowledge on germ cell tumors (GCT) has increased dramatically. Tumors that at one time were supposed to originate exclusively from certain anatomic areas are now thought to occur in ubiquitous distribution. Nevertheless, because of their similar histopathologic features, the conventional classic evaluation of these patients will require careful clinical history as well as complete physical and radiologic evaluation. The emphasis in this manuscript will be to highlight the occurrence and overall characteristics of one of the most common GCTs in the mediastinal region-seminoma. A more detailed discussion of mediastinal GCTs is well beyond the scope of this review. PMID- 22313836 TI - Anatomic pathology laboratory information systems: a review. AB - The modern anatomic pathology laboratory depends on a reliable information infrastructure to register specimens, record gross and microscopic findings, regulate laboratory workflow, formulate and sign out report(s), disseminate them to the intended recipients across the whole health system, and support quality assurance measures. This infrastructure is provided by the Anatomical Pathology Laboratory Information Systems (APLIS), which have evolved over decades and now are beginning to support evolving technologies like asset tracking and digital imaging. As digital pathology transitions from "the way of the future" to "the way of the present," the APLIS continues to be one of the key effective enablers of the scope and practice of pathology. In this review, we discuss the evolution, necessary components, architecture and functionality of the APLIS that are crucial to today's practicing pathologist and address the demands of emerging trends on the future APLIS. PMID- 22313837 TI - The use of neuroimaging to guide the histologic diagnosis of central nervous system lesions. AB - Recent advances in neuroimaging techniques, particularly in magnetic resonance imaging, have led to substantially improved spatial anatomic resolution such that subtle or small central nervous system lesions, which could go undetected on gross examination of brain sections, are now readily identified on imaging. Although neuroimaging is generally considered the surrogate of gross neuropathology, it is still not a substitute for tissue diagnosis. Rather, it can be a valuable tool for the surgical pathologist in the process of formulating a differential diagnosis based on location and imaging features, as well as in identifying radiologic/pathologic discordance, such as the possible undersampling of a heterogenous glioma, which could lead to underestimation of the tumor grade. The following review focuses on the application of neuroimaging techniques, mainly magnetic resonance imaging, to the histologic diagnosis of central nervous system lesions, and the correlation of imaging features of infiltrative gliomas with histologic findings pertinent to tumor grading. The use of advanced functional magnetic resonance methods, specifically diffusion-weighted imaging, perfusion-weighted imaging, and magnetic resonance spectroscopy is also discussed, as well as the common pitfalls in imaging interpretation. PMID- 22313838 TI - Changing the term "breast tumor resembling the tall cell variant of papillary thyroid carcinoma" to "tall cell variant of papillary breast carcinoma". AB - Papillary lesions of the breast continue to be a diagnostic challenge because of the wide morphologic spectrum that may be encountered in these lesions. A rare entity termed "breast tumor resembling the tall cell variant of papillary thyroid carcinoma" is considered to be a subtype of papillary carcinoma of the breast. It is characterized by distinct morphologic features, setting it apart from typical papillary carcinoma of the breast. Its resemblance to papillary thyroid carcinoma in conjunction with the established terminology may cause confusion, resulting in unnecessary ancillary studies to exclude the association of this lesion with papillary thyroid carcinoma. As immunohistochemical and molecular studies have shown no evidence to support any association between this entity and papillary thyroid carcinoma, we propose to change the current terminology of "breast tumor resembling the tall cell variant of papillary thyroid carcinoma" to the term "tall cell variant of papillary breast carcinoma." PMID- 22313839 TI - Crescentic Glomerulonephritis: an update on Pauci-immune and Anti-GBM diseases. AB - Crescentic glomerulonephritis (GN) in a renal biopsy is a widely accepted "critical diagnosis" in Anatomic Pathology practice. Prompt biopsy evaluation and notification of the referring physician is essential to facilitate rapid therapeutic intervention. The differential diagnostic categories of crescentic GN include pauci-immune GN, anti-glomerular basement membrane (GBM) nephritis and immune complex-mediated GN, distinguished from one another by immunofluorescence and electron microscopic study of the renal biopsy. Immune complex-mediated GN is characterized by abundant glomerular deposits and encompasses several diseases including but not limited to lupus nephritis, cryoglobulinemic GN and immunoglobulin A nephropathy. Pauci-immune GN, with paucity of deposits, correlates closely with antineutrophil cytoplasmic antibody disease due to the identifiable circulating pathogenic antineutrophil cytoplasmic antibody in most patients. Recent studies have identified other antibodies in pauci-immune GN and implicated infectious organisms in triggering autoimmunity in a susceptible host by molecular mimicry of host antigens. Anti-GBM nephritis is a rare but potentially life-threatening autoimmune disease with circulating antibodies against GBM epitopes in alpha3 chain of type IV collagen. It is characterized by a linear immunoglobulin G deposition along GBM on immunofluorescence microscopy. Environmental triggers including infections and solvent exposure seem to change the tertiary structure of the type IV collagen alpha345 hexamer in GBM, expose neoepitopes, and initiate autoimmunity. Even in light of advances in understanding of pathophysiology and serologic testing, renal biopsy remains the mainstay of diagnosis of crescentic GN. PMID- 22313840 TI - MUC1 immunoexpression is a virtually constant feature of clear cell renal cell carcinoma metastatic to the pancreas. PMID- 22313841 TI - In reply. PMID- 22313842 TI - The inhibitory effect of ethylenediamine on mushroom tyrosinase. AB - The inhibitory effect of ethylenediamine on both activities of mushroom tyrosinase (MT) at 20 degrees C in a 10 mM phosphate buffer solution (pH 6.8), was studied. L-DOPA and L-tyrosine were used as substrates of catecholase and cresolase activities, respectively. The results showed that ethylenediamine competitively inhibits both activities of the enzyme with inhibition constants (K(i)) of 0.18+/-0.05 and 0.14+/-0.01 MUM for catecholase and cresolase respectively, which are lower than the reported values for other MT inhibitors. For further insight a docking study between tyrosinase and ethylenediamine was performed. The docking simulation showed that ethylenediamine binds in the active site of the enzyme near the Cu atoms and makes 3 hydrogen bonds with two histidine residues of active site. PMID- 22313843 TI - Neck control after definitive radiochemotherapy without planned neck dissection in node-positive head and neck cancers. AB - BACKGROUND: The purpose of this study was to evaluate neck control outcomes after definitive radiochemotherapy without planned neck dissection in node-positive head and neck cancer. METHODS: We retrospectively reviewed medical records of fifty patients with node-positive head and neck cancer who received definitive radiochemotherapy. Twelve patients subsequently underwent neck dissection for suspicious recurrent or persistent disease. A median dose of 70 Gy (range 60 70.6) was delivered to involved nodes. Response evaluation was performed at a median of 5 weeks after completion of radiotherapy. RESULTS: Neck failure was observed in 11 patients and the 3-year regional control (RC) rate was 77.1%. Neck dissection was performed in 10 of the 11 patients; seven of these cases were successfully salvaged, and the ultimate rate of neck control was 92%. The remaining two patients who received neck dissection had negative pathologic results. On univariate analysis, initial nodal size > 2 cm, a less-than-complete response at the primary site, post-radiotherapy nodal size > 1.5 cm, and post radiotherapy nodal necrosis were associated with RC. On multivariate analysis, less-than-complete primary site response and post-radiotherapy nodal necrosis were identified as independent prognostic factors for RC. CONCLUSIONS: The neck failure rate after definitive radiochemotherapy without planned neck dissection was 22%. Two-thirds of these were successfully salvaged with neck dissection and the ultimate neck control rate was 92%. Our results suggest that planned neck dissection might not be necessary in patients with complete response of primary site, no evidence of residual lesion > 1.5 cm, or no necrotic lymph nodes at the 1-2 months follow-up evaluation after radiotherapy. PMID- 22313858 TI - Investigating the effect of high spring incidence of pandemic influenza A(H1N1) on early autumn incidence. AB - A pandemic H1N1 infection wave in the USA occurred during spring 2009. Some hypothesized that for regions affected by the spring wave, an autumn outbreak would be less likely or delayed compared to unaffected regions because of herd immunity. We investigated this hypothesis using the Outpatient Influenza-like Illness (ILI) Network, a collaboration among the Centers for Disease Control and Prevention, health departments, and care providers. We evaluated the likelihood of high early autumn incidence given high spring incidence in core-based statistical areas (CBSAs). Using a surrogate incidence measure based on influenza related illness ratios, we calculated the odds of high early autumn incidence given high spring incidence. CBSAs with high spring ILI ratios proved more likely than unaffected CBSAs to have high early autumn ratios, suggesting that elevated spring illness did not protect against early autumn increases. These novel methods are applicable to planning and studies involving other infectious diseases. PMID- 22313859 TI - Clinical utility of array comparative genomic hybridisation for prenatal diagnosis: a cohort study of 3171 pregnancies. AB - OBJECTIVE: To evaluate the clinical value of prenatal array comparative genomic hybridisation (CGH) in screening for submicroscopic genomic imbalances. DESIGN: Cross-sectional study. SETTING: Tertiary referral centre. POPULATION: From June 2008 to February 2011, 3171 fetuses underwent prenatal array CGH testing and karyotyping at the National Taiwan University Hospital. Indications for invasive prenatal diagnosis included abnormal karyotype, abnormal ultrasound, advanced maternal age and parental anxiety. METHODS: In all, 2497 fetuses were screened with 1-Mb resolution bacterial artificial chromosome array-based CGH, and 674 fetuses with 60-K oligonucleotide array-based CGH. Multiplex ligation-dependent probe amplification, fluorescence in situ hybridization, or 105-K oligonucleotide array CGH provided further confirmation. MAIN OUTCOME MEASURE: Copy number variations identified by array CGH. RESULTS: Array CGH detected numerical chromosome anomalies in 37 (1.2%) fetuses, microdeletion/duplication in 34 (1.1%) fetuses, large deletion/duplication in 13 (0.4%) fetuses, benign copy number changes in 13 (0.4%) fetuses and variation of unknown clinical significance in five (0.2%) fetuses. Array CGH was effective in identifying submicroscopic genomic imbalance in fetuses with de novo balance translocations (2/17, 1.8%), supernumerary marker chromosomes (3/6, 50%), and abnormal prenatal ultrasound findings (33/194, 17.0%). Array CGH detected microdeletions/duplications in 12 fetuses with normal karyotype. CONCLUSION: Prenatal array CGH is effective in screening for submicroscopic genomic imbalance. Array CGH may add 8.2% to the diagnostic field, compared with conventional karyotyping, for fetuses with abnormal ultrasound results, and is particularly useful in fetuses with karyotypic balanced translocation or marker chromosomes. There is a 0.52% baseline risk of submicroscopic genomic imbalance, even in women with an uneventful prenatal examination. PMID- 22313860 TI - Phase II study of cytarabine in men with docetaxel-refractory, castration resistant prostate cancer with evaluation of TMPRSS2-ERG and SPINK1 as serum biomarkers. AB - What's known on the subject? and What does the study add? To date, there has been limited impetus to examine the use of cytarabine in prostate cancer. We presented preliminary laboratory data to suggest its utility in the castration refractory prostate cancer (CRPC) population which, combined with a previous case report, suggested it may have hitherto unrecognized utility in this setting. Embedded in this study was peripheral blood sampling for TMPRSS2-ERG and SPINK1, two genes that are believed to define prostate cancer genotypes, to assess their utility as biomarkers This study suggests that at the delivered doses, cytarabine has limited efficacy and significant myelotoxicity suggesting, it does not have a role in the treatment of docetaxel-refractory CRPC. The presence of serum TMPRSS2 ERG and SPINK1 mRNA biomarkers recovered from blood suggest that their analysis is worthy of further study. OBJECTIVES: To run a phase II clinical trial of cytarabine in men with docetaxel-refractory, castration-resistant prostate cancer (CRPC), based on evidence that cytarabine might be effective in men with abnormalities of ERG oncogenes. To measure mRNA levels of prostate cancer-related genes in blood as biomarkers. PATIENTS AND METHODS: Ten of a planned maximum of 30 men received i.v. cytarabine at doses of 0.25-1g/m(2) at 21-day intervals. The primary endpoint was prostate-specific antigen (PSA) response. Archival tumour samples were assessed by fluorescence in-situ hybridization for TMPRSS2:ERG translocation, and by immunohistochemistry for serine peptidase inhibitor Kazal type 1 (SPINK1). Blood was processed for mRNA quantification of TMPRSS2:ERG (exon1:exon4), SPINK1 and PSA. RESULTS: A PSA response was not observed in any patient. The trial was stopped at the end of stage 1 of a modified Flemming design. The median number of cycles administered was 3. Grade 3-4 haematological toxicity was common. Five patients were subsequently excluded from the study for toxicity, and five for disease progression. Analysis of whole blood mRNA for T1:E4 translocation in TMPRSS2:ERG was consistent with that in the tumour in 8/9 evaluable cases (one was concordantly positive, seven were concordantly negative), SPINK1 results were concordant in 9/10 cases (two were concordantly positive, seven were concordantly negative [P = 0.047 for the predictive value]). There was no correlation between PSA or SPINK protein and their respective mRNA copy levels in blood. CONCLUSIONS: Cytarabine at the doses used is ineffective for men with CRPC. Blood mRNA levels of prostate cancer genes may represent a novel aspect of monitoring prostate cancer and have implications for the understanding of tumour-derived mRNA. PMID- 22313861 TI - TAK-1/p38/nNFkappaB signaling inhibits myoblast differentiation by increasing levels of Activin A. AB - BACKGROUND: Skeletal-muscle differentiation is required for the regeneration of myofibers after injury. The differentiation capacity of satellite cells is impaired in settings of old age, which is at least one factor in the onset of sarcopenia, the age-related loss of skeletal-muscle mass and major cause of frailty. One important cause of impaired regeneration is increased levels of transforming growth factor (TGF)-beta accompanied by reduced Notch signaling. Pro inflammatory cytokines are also upregulated in aging, which led us hypothesize that they might potentially contribute to impaired regeneration in sarcopenia. Thus, in this study, we further analyzed the muscle differentiation-inhibition pathway mediated by pro-inflammatory cytokines in human skeletal muscle cells (HuSKMCs). METHODS: We studied the modulation of HuSKMC differentiation by the pro-inflammatory cytokines interleukin (IL)-1alpha and tumor necrosis factor (TNF)-alpha The grade of differentiation was determined by either imaging (fusion index) or creatine kinase (CK) activity, a marker of muscle differentiation. Secretion of TGF-beta proteins during differentiation was assessed by using a TGF beta-responsive reporter-gene assay and further identified by means of pharmacological and genetic inhibitors. In addition, signaling events were monitored by western blotting and reverse transcription PCR, both in HuSKMC cultures and in samples from a rat sarcopenia study. RESULTS: The pro inflammatory cytokines IL-1alpha and TNF-alpha block differentiation of human myoblasts into myotubes. This anti-differentiation effect requires activation of TGF-beta-activated kinase (TAK)-1. Using pharmacological and genetic inhibitors, the TAK-1 pathway could be traced to p38 and NFkappaB. Surprisingly, the anti differentiation effect of the cytokines required the transcriptional upregulation of Activin A, which in turn acted through its established signaling pathway: ActRII/ALK/SMAD. Inhibition of Activin A signaling was able to rescue human myoblasts treated with IL-1beta or TNF-alpha, resulting in normal differentiation into myotubes. Studies in aged rats as a model of sarcopenia confirmed that this pro-inflammatory cytokine pathway identified is activated during aging. CONCLUSIONS: In this study, we found an unexpected connection between cytokine and Activin signaling, revealing a new mechanism by which cytokines affect skeletal muscle, and establishing the physiologic relevance of this pathway in the impaired regeneration seen in sarcopenia. PMID- 22313862 TI - Screening for measles vaccination in young Japanese non-healthcare workers through self-reported history. AB - OBJECTIVES: The aim of this study was to examine the efficacy of a self administered questionnaire as a prescreening tool to determine the immune status against measles among non-healthcare workers. METHODS: The study subjects were Japanese non-healthcare workers aged 19-30 yr employed at a gas company that underwent an annual health checkup in 2009. Their histories of measles infection, vaccination and possible contact with measles patients were collected through a self-administered questionnaire. The sensitivity and specificity of these self reports were analyzed against a serum anti-measles IgG assay as a gold standard. RESULTS: Of the 509 respondents, 93.3% had immunity against measles. The sensitivity, specificity and positive predictive values for the self-report questionnaire were 14.1, 97.1 and 98.5% for infection history; 39.2, 73.5 and 95.4% for vaccination history; and 13.1, 85.3 and 92.5% for possible contact history, respectively. CONCLUSIONS: Self-reported histories poorly predicted immune status against measles in young Japanese non-healthcare workers. The results suggest that a universal serological screening is still the most effective method available to identify those who require measles vaccination. PMID- 22313863 TI - The effort-reward imbalance questionnaire in Greek: translation, validation and psychometric properties in health professionals. AB - OBJECTIVES: The aim of the present study was to translate, adapt and validate the Effort-reward imbalance (ERI) questionnaire in a sample of Greek healthcare professionals. METHODS: An internationally recommended methodology was followed to perform translation of the ERI instrument into the Greek language. The questionnaire was then randomly administered to 600 Greek physicians, nurses, physiotherapists and laboratory staff, and 456 questionnaires with no missing data on the ERI items were returned (76% response rate). Tool validation included assessment of internal consistency, factorial structure, discriminant validity and presence of floor or ceiling effects. Criterion validity was demonstrated by investigating the association of theoretically relevant ERI summary measurements with respondents' self-rated health. RESULTS: The Greek version of the ERI questionnaire showed good psychometric properties. Cronbach's alpha values were 0.79, 0.72 and 0.75 for the three ERI scales of effort, reward and overcommitment respectively. Exploratory factor analysis yielded a 5-factor solution that closely reflected the original theoretical ERI model. Significant associations were found between respondents' age, gender and specific occupation with ERI scores. ERI ratio and "overcommitment" scores in the highest tertiles were associated with elevated odds ratios (OR) of below-average self-rated health (OR=5.38, 95% confidence intervals 1.77 to 16.38, p=0.003, and OR=3.41, 95% confidence intervals 1.39 to 8.38, p=0.007, respectively). CONCLUSIONS: The translated and adapted Greek version is comparable with the original ERI instrument in terms of validity and factorial structure and is suitable for assessment of the psychosocial work environment of Greek healthcare professionals. PMID- 22313864 TI - Population compliance with national dietary recommendations and its determinants: findings from the ORISCAV-LUX study. AB - The objective of the present study was to determine the proportion of adults meeting national recommendations for food and nutrient intake and to identify the demographic, socio-economic and behavioural factors that may contribute to weaken dietary compliance. ORISCAV-LUX is a cross-sectional study that took place in Luxembourg (2007-8). A representative stratified random sample of 1352 adults aged 18-69 years participated in the nationwide cardiovascular health survey. A FFQ was used to estimate food intake. Radar charts were built to compare graphically the compliance of the participants with different key dietary guidelines on the same set of axes. The thirteen food- and nutrient-based recommendations were scored and summed to create a recommendation compliance index (range -0.5 to 14). Ordinal logistic regression analyses were performed to determine the factors contributing to poor dietary compliance. Several food- and nutrient-based guidelines were insufficiently respected compared with others. The greatest gaps occurred in the adherence to grain and dairy product consumption guidelines, as well as to total fat and notably to SFA recommendations. Age, country of birth, economic status, smoking status and subject's awareness of the importance of balanced meals emerged as independently associated with weak dietary compliance. Obese subjects conformed more to dietary recommendations compared with normal-weight subjects. The findings underscore the need for specific nutrition education messages along with targeted interventions. Efforts should be continued to increase population awareness of the importance of a healthy lifestyle and a balanced diet. PMID- 22313865 TI - Glycodelin-A interferes with IL-2/IL-2R signalling to induce cell growth arrest, loss of effector functions and apoptosis in T-lymphocytes. AB - BACKGROUND: The progesterone-regulated glycoprotein glycodelin-A (GdA), secreted by the decidualized endometrium at high concentrations in primates, inhibits the maternal immune response against fetal antigens and thereby contributes to the tolerance of the semi-allogenic fetus during a normal pregnancy. Our earlier studies demonstrated the ability of GdA to induce an intrinsic apoptotic cascade in CD4(+) T-lymphocytes and suppress the cytolytic effector function of CD8(+) T lymphocytes. In this report, we investigated further into the mechanism of action of GdA controlling perforin and granzyme B expression in CD8(+) T-lymphocytes and the mechanism of action of GdA leading to lymphocyte death. METHODS: Flow cytometry analysis was performed to check for the surface expression of interleukin-2 receptor alpha (IL-2Ralpha) and intracellular eomesodermin (Eomes) in activated T-lymphocytes, whereas quantitative RT-PCR analysis was used to find out their mRNA profile upon GdA treatment. Western analysis was carried out to confirm the protein level of Bax and Bcl-2. RESULTS: GdA reduces the surface expression of the high-affinity IL-2R complex by down-regulating the synthesis of IL-2Ralpha (CD25). This disturbs the optimal IL-2 signalling and decreases the Eomes expression, which along with IL-2 directly regulates perforin and granzymes expression. Consequently, the CD8(+) T-lymphocytes undergo growth arrest and are unable to mature into competent cytotoxic T-lymphocytes. In the CD4(+) T lymphocytes, growth factor IL-2 deprivation leads to proliferation inhibition, decreased Bcl-2/enhanced Bax expression, culminating in mitochondrial stress and cell death. CONCLUSIONS: GdA spurs cell cycle arrest, loss of effector functions and apoptosis in different T-cell subsets by making T-lymphocytes unable to respond to IL-2. PMID- 22313866 TI - Failure of a combined clinical- and hormonal-based strategy to detect early spermatogenesis and retrieve spermatogonial stem cells in 47,XXY boys by single testicular biopsy. AB - BACKGROUND: Although germ cells in boys with Klinefelter syndrome (KS) are reduced in number as early as infancy, a severe germ cell loss occurs during mid puberty. Therefore, we wanted to detect spermatogenesis at an early stage and investigate the strategy of preserving spermatozoa and/or testicular spermatogonial stem cells in adolescents with KS when signs of deteriorating spermatogenesis are observed. METHODS: Tanner staging, testicular size, serum inhibin B and spermaturia were assessed every 4 months before the attempt to procure gametogenic cells in seven non-mosaic 47,XXY adolescents, aged between 10 and 16 years. RESULTS: Despite an increasing testis volume in the youngest and a Tanner staging of more than three in the oldest patients, no spermaturia was observed. In two patients serum inhibin B increased gradually, while in all others a rather rapid but variable decline was observed at different ages. No spermatozoa were observed after electroejaculation. No spermatocytes or spermatids were found at microscopic examination of single biopsies, while spermatogonia were identified in four subjects, three of whom had measurable serum inhibin B. Massive fibrosis and hyalinization were observed in all biopsies. CONCLUSION: No spermatogenesis was documented in non-mosaic 47,XXY adolescents either by spermaturia, electroejaculation or testicular biopsy. Neither clinical nor hormonal parameters were of value in determining the timing for optimal spermatogonial stem cell retrieval. More data are needed to elucidate the potential role of testicular tissue cryopreservation in adolescents with KS. Therefore, at present, the cryopreservation of testes tissue for clinical reasons should not be recommended. PMID- 22313867 TI - Heated spermatozoa: effects on embryonic development and epigenetics. AB - BACKGROUND: Sperm chromatin is highly condensed and relatively resistant to chemical and physical treatments. The purpose of this study was to explore the highest temperature that sperm can tolerate and still produce live offspring. METHODS: Mouse sperm were heated in a water bath at 50, 65, 80 or 95 degrees C for 30 min before they were microinjected into mouse oocytes. Fertilization, embryo development and 1-cell embryo karyotypes were evaluated. Epigenetic reprogramming including DNA methylation and histone H3K4-trimethylation were evaluated by immunofluorescent staining. RESULTS: The ability of mouse sperm to activate the egg after ICSI was heat sensitive; only 20% of eggs were activated by sperm that had been heated to 50 degrees C and none was activated by sperm heated to 80 degrees C. However, if eggs were activated artificially, mouse sperm subjected to 80 degrees C for 30 min were able to produce live offspring, while 95 degrees C treatment disabled sperm decondensation after ICSI. Once the heat treated sperm nucleus had developed into a pronucleus, sperm chromatin was able to undergo normal active DNA demethylation and histone methylation. Aberrant chromosome rates increased from 16.3 to 100% when the temperature was raised from 50 to 95 degrees C. CONCLUSIONS: Heat treatment destroys integrity of sperm chromatin in a temperature-dependent manner. Eighty degree Celsius was the highest temperature that mouse sperm could withstand and still produce live offspring. PMID- 22313868 TI - Tailored expectant management: a nationwide survey to quantify patients' and professionals' barriers and facilitators. AB - BACKGROUND: Prognostic models for natural conception help to identify subfertile couples with high chances of natural conception, who do not need fertility treatment yet. The use of such models and subsequent tailored expectant management (TEM) is not always practiced. Previous qualitative research has identified barriers and facilitators of TEM among patients and professionals. The aim of this study was to assess the prevalence of those barriers and facilitators and to evaluate which factors predict patients' appreciation of TEM and professionals' adherence to TEM. METHODS: We performed a nationwide survey. Based on the previously identified barriers and facilitators two questionnaires were developed and sent to 195 couples and 167 professionals. Multivariate analysis was performed to evaluate which factors predicted patients' appreciation of TEM and professional adherence to TEM. RESULTS: In total, 118 (61%) couples and 117 (70%) professionals responded and 96 couples and 117 professionals were included in the analysis. Patients' mean appreciation of TEM was 5.7, on a 10-point Likert scale. Patients with a lower appreciation of TEM had a higher need for patient information (P = 0.047). The professionals reported a mean adherence to TEM of 63%. Adherence to TEM was higher when professionals were fertility doctors (P = 0.041). Facilitators in the clinical domain were associated with a higher adherence to TEM (P = 0.091). Barriers in the professional domain had a negative impact on adherence to TEM (P = 0.008). CONCLUSIONS: The limited implementation of TEM is caused by both patient and professional-related factors. This study provides practical tools to improve the implementation of TEM. PMID- 22313869 TI - Understanding the perceptions of and emotional barriers to infertility treatment: a survey in four European countries. AB - BACKGROUND: Infertility can significantly impact women's lives and personal relationships. Despite the negative impact of infertility, a significant number of women who are struggling to conceive do not consult a physician. This cross sectional survey was conducted to determine the emotional impact of infertility on women to identify which aspects of fertility treatment contribute to the psychological stress experienced by so many patients and to identify barriers to seeking treatment. METHODS: Women (n = 445; 18-44 years) who had received fertility treatment within the past 2 years or were having trouble conceiving but had not received treatment, completed a 15-min survey online. RESULTS: Participants were from France (n = 108), Germany (n = 111), Italy (n = 112) and Spain (n = 114). Responses indicated that infertility causes a range of emotions and can strain relationships. Women who had received treatment were more likely to feel hopeful (26 versus 21%) and closer to their partner than women not in treatment (33 versus 19%, P < 0.05). Most women delayed starting treatment because of a desire to conceive naturally, and on the advice of physicians. Women aged >=35 years took longer to seek help with their fertility issues. Injection related anxiety was the second greatest barrier to treatment. CONCLUSIONS: This study has provided insight into the physical and psychological challenges of infertility treatments and permitted a better understanding of the factors that impact patient lives. A treatment protocol with minimal injections and provision of additional information may lessen the emotional impact and challenges of infertility and contribute to patient satisfaction with fertility treatment protocols. PMID- 22313870 TI - Human papillomavirus sperm infection and assisted reproduction: a dangerous hazard with a possible safe solution. AB - BACKGROUND: Human papillomavirus (HPV) infection has been demonstrated in the sperm of a large percentage of sexually active males and is associated with an impairment of sperm parameters, with a particular negative impact on sperm motility, suggesting a possible role in male infertility. Conventional sperm selection techniques have a low efficiency in removing HPV. METHODS: Evaluation of sperm parameters, terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling test to evaluate DNA fragmentation and fluorescence in situ hybridization or immunohistochemistry for HPV were performed on semen samples from infected patients (n= 22), control subjects (n= 13) and on pooled control sperm samples incubated with HPV16-L1 (HPV capsid), before and after direct swim up and modified swim-up (with added Heparinase-III). Moreover, cytofluorimetry for HPV detection was performed in pooled sperm pre- and post-incubation with HPV 16-L1 before and after direct and modified swim-up. Statistical analysis was performed with a two-tailed Student's t-test. RESULTS: Direct swim-up reduces the number of HPV-infected sperm by ~24% (P< 0.01), while modified swim-up is able to remove completely HPV DNA both from naturally and artificially infected sperm. Enzymatic treatment with Heparinase-III tended to decrease sperm motility, viability and DNA integrity but the effects were not significant. CONCLUSIONS: This study shows that Heparinase-III treatment seems not to affect spermatozoa in vitro and suggests that this treatment should be investigated further as a means of preparing sperm from patients who are infected with HPV in order to reduce the risk of HPV infection when using assisted reproduction techniques. PMID- 22313871 TI - Human chorionic gonadotrophin stimulation test as a predictor of ovarian response and pregnancy in IVF cycles stimulated with GnRH agonist gonadotrophin treatment: a pilot study. AB - BACKGROUND: Recent evidence supports a specific and broad role of androgen produced by theca cells in reproductive physiology. This pilot study evaluated the usefulness of hCG theca stimulation test in predicting ovarian response and pregnancy. METHODS: Prospective cohort study including 80 infertile women treated with IVF/ICSI. On Day 3 of the menstrual cycle preceding, the first IVF/ICSI cycle a blood sample was drawn to evaluate baseline FSH, estradiol (E(2)), 17 hydroxy-progesterone, androstenedione and testosterone levels. All women then received 250 ug recombinant hCG s.c. and underwent a second blood sampling 24 h after hCG injection to measurement steroid serum levels. RESULTS: Percentage increment of E(2) but not its precursors was significantly higher in normo responders and pregnancy cycles than in poor responders and non-pregnancy cycles (P = 0.03 and P = 0.02, respectively) diagnostic accuracy being 67 and 75%, respectively. The percentage increase in E(2) thus still fails in as many as 33 and 25% of patients in predicting ovarian response and pregnancy, respectively. In addition, E(2) concentrations are poorly reproducible and a wide range of variation in all serum steroids investigated-including E(2)-after hCG injection was observed. CONCLUSIONS: The predictive power of the hCG test is based on E(2) but not androgen response to hCG injection. This test cannot be recommended in routine clinical practice because it is too laborious for screening purposes, shows great variability in the response obtained and its overall accuracy is not better than that reported for other available markers of ovarian reserve. The use of the currently available markers, antral follicle count and anti-Mullerian hormone, is therefore recommended. PMID- 22313872 TI - Effect of cryopreservation and transplantation on the expression of kit ligand and anti-Mullerian hormone in human ovarian tissue. AB - BACKGROUND: Although cryopreservation and transplantation of ovarian tissue represent a promising alternative to safeguard fertility in cancer patients, low recovery rates of oocytes aspirated from antral follicles and a significant number of empty follicles have been observed in women with transplanted frozen thawed ovarian tissue. In order to understand how freezing and/or grafting may affect follicular development, the follicular expression of kit ligand (KL) and anti-Mullerian hormone (AMH), two key factors activating and inhibiting follicle growth, were assessed after long-term grafting in severe combined immunodeficient (SCID) mice. METHODS: Ovarian biopsies from eight patients were used for fresh and frozen-thawed tissue xenografting in 13 SCID mice for a period of 28 weeks, including 2 weeks of gonadotrophin stimulation. KL, AMH and proliferating cell nuclear antigen (PCNA) immunostaining were quantified before and after grafting in the two treatment groups (fresh and frozen-thawed grafted ovarian tissue). RESULTS: Lower expression of KL was found in primordial and primary follicles after grafting of both fresh and frozen-thawed tissue. Consistent expression of AMH was found in most growing follicles at a similar rate in both graft types. In fresh and frozen-thawed grafts, 13-14% of primordial follicles were PCNA positive, indicating a similar maintenance of quiescent follicles despite follicle activation. CONCLUSIONS: Grafting and/or gonadotrophin stimulation appear to affect the follicular expression of KL, which may alter oocyte quality. AMH expression in growing follicles after ovarian tissue transplantation may be one of the factors contributing to the preservation of resting follicles in 28 week-old grafts. PMID- 22313873 TI - A facile titanium glycolate precursor route to mesoporous Au/Li4Ti5O12 spheres for high-rate lithium-ion batteries. AB - A facile, green strategy is explored to synthesize mesoporous Au/Li(4)Ti(5)O(12) spheres based on in situ conversion of titanium glycolate in LiOH aqueous solution. Compared with TiO(2) precursors, titanium glycolate possesses some strengths: (i) fast and easy preparation; (ii) direct reaction with LiOH without introduce of TiO(2) impurity. In the synthesis, the produced chemical waste is only the mixed solvent of acetone and ethylene glycol (EG). Furthermore, acetone and EG in chemical waste can be easily separated by distillation and reused in the next synthesis process due to the great difference between their boiling points. In particular, the as-prepared mesoporous Au/Li(4)Ti(5)O(12) spheres combines the advantages of large specific surface area (166 m(2)/g) and good electronic conduction enhanced by Au nanoparticles when used as an anode electrode material. The electrochemical tests show that the mesoporous Au/Li(4)Ti(5)O(12) spheres display excellent high rate capability and cycling performance. PMID- 22313874 TI - Cross-talk between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression. AB - The tumor microenvironment is a complex milieu of tumor and host cells. Host cells can include tumor-reactive T cells capable of killing tumor cells. However, more frequently the tumor and host components interact to generate a highly immune suppressive environment that frustrates T cell cytotoxicity and promotes tumor progression through a variety of immune and non-immune mechanisms. Myeloid derived suppressor cells (MDSC) are a major host component contributing to the immune suppressive environment. In addition to their inherent immune suppressive function, MDSC amplify the immune suppressive activity of macrophages and dendritic cells via cross-talk. This article will review the cell-cell interactions used by MDSC to inhibit anti-tumor immunity and promote progression, and the role of inflammation in promoting cross-talk between MDSC and other cells in the tumor microenvironment. PMID- 22313875 TI - Familial and large-scale case-control studies identify genes associated with nasopharyngeal carcinoma. AB - Nasopharyngeal carcinoma (NPC) is an epithelial malignancy and has a remarkable geographic distribution, which is highly prevalent in southern China, Southeast Asia, and North Africa. Although most of the NPC are sporadic cases, the familial clustering of NPC has been demonstrated worldwide. Accumulating studies have proposed that the etiology of NPC is multi-stage and multi-factorial, involving genetic lesions, Epstein-Barr virus infection, and environmental exposure. Genetic variations result in differences in gene function, which in turn lead to different susceptibility to disease. Many studies have been carried out to dissect the genetic variants that contribute to NPC susceptibility. This article reviews the current progress of genetic studies to identify genes associated with NPC, focusing on the familial linkage and large-scale case-control study designs. PMID- 22313876 TI - Regulation of suppressive function of myeloid-derived suppressor cells by CD4+ T cells. AB - Myeloid derived suppressor cells play a critical role in T cell suppression in cancer. Here, we discuss the mechanisms of how MDSC suppress CD4(+) or CD8(+) T cells in an antigen dependent or non-dependent manner. PMID- 22313878 TI - A recent update in research on the antihepatotoxic potential of medicinal plants. AB - Hepatic damage is a global metabolic and epidemic disease, affecting essential biochemical activities in almost every age group. Conventional drugs used in the treatment of liver disorders are often inadequate. Also, the spectrum of liver abnormalities caused by allopathic drugs is found to be broad. In view of severely undesirable side effects of synthetic agents, it is necessary to search for alternative drugs for the treatment of liver diseases to replace the currently used drugs, which are of doubtful efficacy and safety. Therefore, there is growing focus to follow systematic research methodology and to evaluate scientific basis for the traditional herbal medicines that are claimed to possess hepatoprotective activities. Use of herbal drugs in the treatment of liver diseases has a long tradition, especially in Eastern medicine and can be traced back as far as 2100 B.C. in ancient China (Xia Dynasty) and India (Vedic period), but evidence for efficacy is sparse. The current study is aimed at providing an overview of clinical and experimental studies carried out on the most effective and commonly used hepatoprotective plants and their beneficial aspects. PMID- 22313877 TI - DICER-like proteins and their role in plant-herbivore interactions in Nicotiana attenuata. AB - DICER-like (DCL) proteins produce small RNAs that silence genes involved in development and defenses against viruses and pathogens. Which DCLs participate in plant-herbivore interactions remains unstudied. We identified and stably silenced four distinct DCL genes by RNAi in Nicotiana attenuata (Torrey ex. Watson), a model for the study of plant-herbivore interactions. Silencing DCL1 expression was lethal. Manduca sexta larvae performed significantly better on ir-dcl3 and ir dcl4 plants, but not on ir-dcl2 plants compared to wild type plants. Phytohormones, defense metabolites and microarray analyses revealed that when DCL3 and DCL4 were silenced separately, herbivore resistance traits were regulated in distinctly different ways. Crossing of the lines revealed complex interactions in the patterns of regulation. Single ir-dcl4 and double ir-dcl2 ir dcl3 plants were impaired in JA accumulation, while JA-Ile was increased in ir dcl3 plants. Ir-dcl3 and ir-dcl4 plants were impaired in nicotine accumulation; silencing DCL2 in combination with either DCL3 or DCL4 restored nicotine levels to those of WT. Trypsin proteinase inhibitor activity and transcripts were only silenced in ir-dcl3 plants. We conclude that DCL2/3/4 interact in a complex manner to regulate anti-herbivore defenses and that these interactions significantly complicate the already challenging task of understanding smRNA function in the regulation of biotic interactions. PMID- 22313879 TI - [Biological research evaluating the Chinese medical theory of the association of the kidney with the ears]. AB - "Association of the kidney with the ears" is central to the traditional Chinese medical (TCM) theory of the viscera and their manifestations. Previous studies have shown that thyroxin, aldosterone, calcium and iron might be the material basis of the correlation between the kidney and the ears. Due to restriction in research techniques and methods, there has been no further progress in this research field, whose modern biological mechanisms and scientific connotations have not been explained clearly. In recent years, the progress of biological techniques and research on kidney essence provided promising opportunities for research of the association between the kidney and the ears. This article summarized the study progress of "association of the kidney with the ears" theory and posed some meaningful study thoughts. Presbycusis is a kind of degenerative disease caused by aging, which is one aspect of aging of the human body. Because aging is considered as physiological "kidney deficiency", presbycusis can be regarded as a model of "kidney deficiency" deafness. In conclusion, investigating the correlation between "kidney deficiency" and presbycusis using biotechnology systems combined with "essence of kidney", should provide a sound basis for study of the theory of the relationship between the kidney and the ears. This will provide new and valuable information for the modern biological research about the theory of visceral associations in TCM. PMID- 22313880 TI - [Research and application progress of the infrared heating effects of moxibustion]. AB - Moxibustion therapy is a commonly used external treatment method for numerous conditions and general health care. Besides the effects of the drugs, infrared heat and radiation spectrum are also the manner of action. By collecting the literature about thermal radiation and infrared spectrum features of moxibustion, the author reported the novel studies on the thermal effect of moxibustion including factors that impacted the temperature, infrared spectrum features, apparatus based on infrared technology employed in clinic for moxibustion and characteristics of temperature sensitivity. The author also identified some existing problems and provided advice for future application and research. PMID- 22313881 TI - [Systematic review and meta-analysis of randomized controlled trials of Chinese herbal medicine in treatment of multiple sclerosis]. AB - BACKGROUND: Chinese herbal medicine (CHM) has been widely used in the treatment of multiple sclerosis (MS). However, there is no systematic review to assess the efficacy and safety of CHM. OBJECTIVE: To systematically evaluate the efficacy and safety of CHM in the treatment of MS. SEARCH STRATEGY: Literature was searched from the China National Knowledge Infrastructure Database, the Chinese Biomedical Database (SinoMed), the Chongqing VIP Chinese Science and Technology Periodical Database, Wanfang Data, PubMed and the Cochrane Library. The time limitation ran from the commencement of each database to March 15, 2011. INCLUSION CRITERIA: Randomized controlled trials (RCTs) testing CHM alone or in combination with Western medicine (WM) against WM or placebo used alone were included. DATA EXTRACTION AND ANALYSIS: Two authors collected the data respectively. The assessment of methodological quality was based on the Cochrane Handbook and the data were analyzed by using RevMan 5.1.0 software. The efficacy measure was mean difference (MD) with a 95% confidence interval (CI). RESULTS: After screening of the search results, 16 eligible RCTs with 913 cases were included. The included trials were all of low quality. Thirteen studies adopted Kurtzke Extended Disability Status Scale (EDSS) and two of them showed that EDSS in the treatment group was lower than that in the control group, and the MD and 95% CI were -0.88 (-1.26,-0.50). We performed descriptive analysis on the other eight studies which showed that EDSS of the treatment group was lower than that of the control group. Five studies adopted recurrent frequency and two of them showed that recurrent frequency in the treatment group was lower than that in the control group, and the MD and 95% CI were -0.34 (-0.52,-0.16). We performed descriptive analysis on the other three studies which showed that EDSS in the treatment group was lower than that in the control group. Analyses of secondary outcomes such as clinical symptom score, neurological sign score and immune indexes showed that integrated TCM and WM was more effective than WM treatment alone. The studies displayed that the number or range of magnetic resonance imaging lesion of the treatment group was lower than that of the control group, but there was no statistical significance. The reported adverse events in the CHM group were less than those in the control group. CONCLUSION: CHM could improve neurological signs, clinical symptoms and immune indexes, and reduce recurrent frequency. The reported adverse events in the CHM group were less than those in the control group. However, further well-designed research is needed to evaluate the beneficial effects of CHM. PMID- 22313882 TI - Estimation of sample size and testing power (part 5). AB - Estimation of sample size and testing power is an important component of research design. This article introduced methods for sample size and testing power estimation of difference test for quantitative and qualitative data with the single-group design, the paired design or the crossover design. To be specific, this article introduced formulas for sample size and testing power estimation of difference test for quantitative and qualitative data with the above three designs, the realization based on the formulas and the POWER procedure of SAS software and elaborated it with examples, which will benefit researchers for implementing the repetition principle. PMID- 22313883 TI - [A brief introduction to Appraisal of Guidelines for Research and Evaluation II]. AB - Clinical practice guidelines play an important role in practitioner and patient decisions regarding appropriate clinical health care and in health policy formation. In the guideline development process, inappropriate methodologies and development strategies significantly influence the quality of guidelines; therefore, research and evaluation of guidelines have great significance. The original Appraisal of Guidelines for Research and Evaluation (AGREE) instrument was published in 2003 by a group of international guideline developers and researchers. AGREE has important significance for the quality guarantee and successful implementation of guidelines, and has extensively achieved endorsement since 2003. In 2009, The AGREE Collaboration has developed the AGREE II by refining the original AGREE instrument. At present, the AGREE II has already replaced the original AGREE instrument; however, related introduction regarding AGREE II has not been found in China. The authors of this article briefly introduce the AGREE II, and believe that it will add value to research and evaluation of the guidelines. PMID- 22313884 TI - [Assessment of external methods of traditional Chinese medicine in patients with chronic ulcer of the lower extremities: study protocol of a multicenter, randomized, parallel-group, prospective trial]. AB - BACKGROUND: Chronic ulcer of the lower extremities amounts for a grave and serious problem for public health. Western medicine focuses on controlling infection, improving blood circulation, surgical debridement, skin grafting, etc, but there are bottlenecks in the treatment. Traditional Chinese medicine (TCM) has a long history and a legacy of sound clinical efficacy in this area. TCM has developed a unique, effective external theory, and a large number of topical prescriptions and external technology. Through this research, a safe and effective treatment protocol of TCM for chronic ulcer of the lower extremities can be formed. To this end, during China's "Eleventh Five-Year" Plan, special research committees and projects on TCM external treatments and external technologies were established. This study on ulcer of the lower extremities constitutes one of the major research topics. METHODS AND DESIGN: Clinical information of patients with chronic ulcer of the lower extremities will be first collected in a large, multicenter, epidemiological survey. Concurrently, a large multicenter, randomized, parallel-group, prospective study will be launched based on evidence-based medical principles to evaluate the efficacy and safety of external methods for removing carrion, dissolving stasis, reinforcing deficiency and promoting tissue regeneration. The evaluated indexes will include the wound healing percentage for primary outcome, wound healing time, wound healing rate, time and rate of removal of necrotic tissue, and TCM syndromes for secondary outcomes and routine blood test, routine urine test, liver and kidney function, blood mercury content and finally urine mercury content for adverse events. DISCUSSION: In this trial, the authors will evaluate the efficacy and safety of external methods for removing carrion, dissolving stasis, reinforcing deficiency and promoting tissue regeneration in cases of chronic ulcer of the lower extremities for standardizing external therapy of TCM for treatment of this condition, and establishing the clinical assessment system for TCM. TRIAL REGISTRATION NUMBER: The research program was registered in the Chinese Clinical Trial Registry in both English and Chinese in June 2011. REGISTRATION NUMBER: ChiCTR-TRC-11001365. PMID- 22313885 TI - [A prospective cohort study on the influence of high doses of herbs for clearing heat and resolving stasis on survival rates in patients with hepatitis B-related acute-on-chronic liver failure]. AB - BACKGROUND: Hepatitis B-related acute-on-chronic liver failure (ACLF) is a severe clinical syndrome characterized by jaundice, coagulopathy, ascites and hepatic encephalopathy and with a high mortality rate of 65% to 93%. It involves significant ethical issues when a randomized, double-blinded, placebo-controlled clinical study is conducted to such a serious disease. Therefore, a prospective cohort study design was utilized to explore a new treatment modality of applying integrated traditional Chinese and Western medicine. OBJECTIVE: To evaluate the efficacy, safety and recent survival rates of high-dose herbs with the function of clearing heat and resolving stasis, named Qingre Huayu, in patients with hepatitis B-related ACLF with heat toxin stagnation syndrome. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A matched, prospective cohort study was conducted. Participants who met the inclusion criteria were recruited from the Department of Infectious Diseases, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine. Patients were assigned to either an integrated medicine group or a Western medicine group according to their own preference and received either a regime of classic Western medical treatment (control group) or a regime of classic Western medical treatment plus Qingre Huayu herbs (treatment group). The regimes were conducted for 12 weeks. MAIN OUTCOME MEASURES: Survival rates of non-liver transplantation patients were evaluated after 12-week treatment. The levels of total bilirubin (TBiL), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and prothrombin activity (PTA) were detected at baseline and weeks 4, 8 and 12. Scores of traditional Chinese medicine (TCM) syndrome and complications were evaluated at baseline and study completion. Adverse events were recorded. RESULTS: All patients were followed up to the deadline for this study. There were 21 cases (31.8%) who died in the treatment group (n=66) and 19 cases (59.4%) in the control group (n=32). Significant difference (X(2)=6.775, P<0.01) was found in comparing the survival and death rates between the two groups by X(2) test. At 12 weeks, mean survival time of the two groups was 69.9 and 47.2 d respectively; cumulative survival rate of patients in the treatment group was higher than that of patients in the control group (P<0.01). Levels of TBiL, ALT, AST, ALB and PTA at weeks 4, 8 and 12 in the treatment group were superior to those in the control group with statistical significance (P<0.01 or P<0.05). In comparison of the TCM syndrome scores at week 12, the average score of the TCM syndrome of the treatment group (n=45) was 7.52+/-2.41, lower than 18.34+/-4.36 of the control group (n=13), and the difference was significant (t=8.784, P<0.01). Complication incidences after 12 weeks of treatment were statistically different between the treatment group (n=45) and the control group (n=13) by X(2) test (P<0.05 or P<0.01). Incidence rates of ascites, infection and hepatic encephalopathy accounted for 22.22%(10/45) and 69.23% (9/13), 8.89% (4/45) and 53.85% (7/13), and 11.11% (5/45) and 46.15% (6/13) in the two groups respectively. The incidence rates of adverse events in the treatment group and the control group were 0.00% and 12.50% respectively and the difference was statistically significant (X(2)=5.705, P<0.05). No drug-related adverse events were found in blood, urine and stool routine tests, renal function test and electrocardiography. CONCLUSION: High doses of Qingre Huayu herbs can significantly improve liver function and coagulation function, reduce complications, and reduce mortality in patients with hepatitis B-related ACLF. PMID- 22313886 TI - Specificity of auricular acupoints in reflecting changes of qi and blood measured by diffuse reflectance spectroscopy. AB - OBJECTIVE: This study aimed to assess the specificity of auricular acupoints in responding to changes of qi and blood which, in traditional Chinese medicine, are considered as the fundamental substances in the human body for sustaining normal vital activity. METHODS: A miniature fiber optic system was used to invasively measure the diffuse reflectance spectra of three auricular acupoints, namely, Uterus (TF2), Gan (CO12) and Neifenmi (CO18), at different stages of menstruation, when the female body exhibits regular changes of qi and blood. The spectra of different acupoints were compared to find their difference in responding changes of qi and blood, especially the reflectivity of absorption peaks of hemoglobin. RESULTS: The reflectivity of the same auricular acupoint during menstruation is higher than that before and after menstruation, and this trend is more obvious for the Uterus point compared with the points Gan and Neifenmi. The average reflectivity of the Uterus point during menstruation was significantly higher than that before or after menstruation (P<0.01). The D values during and after menstruation of the Uterus point were greater than those of the points Gan and Neifenmi at 544.06 and 577.47 nm, respectively (P<0.05). CONCLUSION: The diffuse reflectance light of auricular acupoints changes as qi and blood fluctuates, and there is relative specificity among different auricular acupoints in reflecting changes of qi and blood. The Uterus point may be the most sensitive auricular acupoint in reflecting uterus function and subsequent changes of qi and blood. PMID- 22313887 TI - [Effects of the mixture of Swertia pseudochinensis Hara and Silybum marianum Gaertn extracts on CCl(4)-induced liver injury in rats with non-alcoholic fatty liver disease]. AB - OBJECTIVE: To study the mechanism of liver injury induced by carbon tetrachloride (CCl(4)) in rats with non-alcoholic fatty liver disease (NAFLD), and the therapeutic effects of the extract mixture of Dangyao (Swertia pseudochinensis Hara) and Shuifeiji (Silybum marianum Gaertn) on NAFLD rats with liver injury. METHODS: Male Wistar rats were randomized into normal control group, CCl(4) group, high-fat diet group, high-fat diet plus CCl(4) injection group (model group), diammonium glycyrrhizinate group and extract mixture group. Except the normal control and CCl(4) groups, rats were fed with high-fat diet (88% normal chow, 10% lard and 2% cholesterol) to induce NAFLD. Diammonium glycyrrhizinate and extracts were given by gavage. After eight weeks, a nonlethal dose of CCl(4) was injected intraperitoneally to all rats except the normal and high-fat diet groups. And 48 h later, all rats were sacrificed, and serum and liver tissues were collected for further study. Paraffin-processed liver tissue was stained with hematoxylin-eosin (HE) to observe the pathological changes. Serum alamine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. The levels of triacylglycerol (TAG), malondialdehyde (MDA) and glutathione (GSH) in liver tissues were also examined. Expression of uncoupling protein 2 (UCP2) was determined by reverse transcription-polymerase chain reaction and Western blotting. RESULTS: Liver sections stained with HE showed that the histopathological changes in the normal control group and the CCl(4) group were mild; massive hepatosteatosis diffusing in lobules was shown in the high-fat diet groups; steatosis, hepatocellular ballooning degeneration and inflammatory infiltration were severe around the central vein in sections of the model group. Compared with the model group, hepatosteatosis and ballooning were significantly attenuated in the treatment groups. Levels of serum ALT and AST, contents of TAG and MDA and the UCP2 expression in liver tissues of the model group increased obviously, while the level of liver GSH decreased. Compared with rats in the model group, the above biomarkers in the treatment groups were improved significantly. CONCLUSION: The mixture of Dangyao and Shuifeiji extracts can decrease the susceptibility and degree of liver injury induced by hepatotoxin in rats with NAFLD. Regulation of the balance of pro- and anti-oxidative stress factors is involved in the mechanism. PMID- 22313888 TI - Preventive effects of Citrus reticulata essential oil on bleomycin-induced pulmonary fibrosis in rats and the mechanism. AB - OBJECTIVE: To investigate the effects of essential oil of Citrus reticulata (EOCR) on proliferation of human embryonic lung fibroblasts (HELFs), and to explore its protective effects on bleomycin (BLM)-induced lung fibrosis in rats. METHODS: Routinely cultured HELFs during the logarithmic phase of growth were divided into control and treated groups, and applied for evaluation of inhibitory activity using methylthiazol tetrazolium (MTT) assay. A rat model of BLM-induced pulmonary fibrosis was used for the evaluation of antifibrotic effect of EOCR. Forty-two Sprague-Dawley rats were randomly divided into normal group, model group, prednisone group and different doses of EOCR groups. BLM was intratracheally instilled into all the rats except those in the normal group, and EOCR was orally given to BLM-treated rats at doses of 25, 50, 100 and 200 mg/kg once per day for four weeks. The rats in the normal group were intratracheally administered the same volume of saline. On the 28th day, rats were sacrificed under anesthesia, and the serum and lung tissues were collected. Superoxide dismutase (SOD) activities and malondialdehyde (MDA) contents in serum and lung tissues were analyzed with corresponding kits; type I collagen (Col I) content in lung tissues was evaluated with enzyme-linked immunosorbent assay; pulmonary fibrosis was assessed by lung histology; protein and mRNA expressions of connective tissue growth factor (CTGF) in lung tissues were measured with immunohistochemical and in situ hybridization semiquantitative image analyses, respectively. RESULTS: The EOCR at different concentrations displayed inhibitory activity on proliferation of HELFs. In in vivo experiment, the weight gain of the rats in groups treated with EOCR at doses of 50, 100 and 200 mg/kg per day was significantly higher than those in the model group at the 7th, 14th, 21st and 28th day (P<0.05 or Plt;0.01). The scores of alveolitis and pulmonary fibrosis in the groups treated with EOCR at doses of 100 and 200 mg/kg per day were significantly lower than those in the model group (Plt;0.01); the SOD levels in serum and pulmonary tissues of the EOCR (50, 100 and 200 mg/kg) groups were markedly increased compared with the model group (Plt;0.01 ), while the MDA levels in both serum and pulmonary tissues were markedly reduced (Plt;0.05); the Col I level in pulmonary tissues of the EOCR (100 and 200 mg/kg per day) groups were markedly lower than that of the model group (Plt;0.01); the protein and mRNA expressions of CTGF in the groups treated with EOCR at doses of 100 and 200 mg/kg per day were down-regulated compared with the model group (Plt;0.01). CONCLUSION: The results indicate that EOCR has preventive effects on BLM-induced pulmonary fibrosis in rats. The mechanism may be via adjusting the unbalance of oxidation and antioxidation, down-regulating CTGF protein and mRNA expressions, and reducing collagen deposition and fibrosis. PMID- 22313889 TI - Potentiated homeopathic drug Arsenicum Album 30C inhibits intracellular reactive oxygen species generation and up-regulates expression of arsenic resistance gene in arsenite-exposed bacteria Escherichia coli. AB - OBJECTIVE: To examine if potentiated homeopathic drug Arsenicum Album 30C (Ars Alb 30C) can reduce sodium arsenite-induced toxicity in Escherichia coli. METHODS: E. coli were exposed to low arsenite insult after they grew up to log phase in standard Luria-Bertani medium. E. coli were treated with 1 or 2 mmol/L sodium arsenite alone (control), or Ars Alb 30C was added to the medium of a subset of sodium arsenite-treated bacteria (drug-treated), or homeopathically agitated alcohol was added to the medium containing a subset of sodium arsenite treated bacteria (placebo-treated). A sub-set of untreated E. coli served as the negative control. Glucose uptake, specific activities of hexokinase, lipid peroxidase (LPO), superoxide dismutase (SOD) and catalase, intra- and extra cellular sodium arsenite content, cell growth, cell membrane potential, DNA damage, intracellular reactive oxygen species (ROS), adenosine triphosphate (ATP) and free glutathione content and expressions of arsB and ptsG gene in normal control, sodium arsenite-treated, drug-treated and placebo-treated E. coli were analyzed. Treatments were blinded and randomized. RESULTS: In sodium arsenite treated E. coli, glucose uptake, intracellular ROS, LPO and DNA damage increased along with decrease in the specific activities of hexokinase, SOD and catalase, intracellular ATP and free glutathione contents and cell membrane potential and growth, and there were increases in expression levels of arsB gene and ptsG gene. Ars Alb 30C administration reduced arsenic toxicity in E. coli by inhibiting generation of ROS and increasing tolerance to arsenite toxicity and cell growth. CONCLUSION: Ars Alb 30C ameliorated arsenic toxicity and DNA damage, validating efficacy of ultra-highly diluted remedies used in homeopathy. PMID- 22313890 TI - Antihyperglycemic and antinociceptive activities of methanolic extract of Euphorbia thymifolia L. whole plants. AB - OBJECTIVE: To study the antihyperglycemic and antinociceptive activities of methanolic extract of the whole plant of Euphorbia thymifolia L., a plant used in folk medicine of Bangladesh for treatment of diabetes and pain. METHODS: Antihyperglycemic activity studies were conducted in glucose-loaded mice by oral glucose tolerance tests. Mice were given various doses of the extract, followed by glucose (2 g/kg body weight), 1 h after administration of the extract. Serum glucose levels were measured 2 h after glucose administration. Antinociceptive activity studies were conducted in intraperitoneally acetic acid-injected mice through measurement of reductions in abdominal writhing times caused by acetic acid-induced gastric pain. Following a period of 1 h after oral administration of various doses of the extract, all mice received intraperitoneal injection of 1% acetic acid at a dose of 10 mL/kg body weight. To ensure bioavailability of acetic acid, a period of 5 min was given to each animal following which period the number of writhings was counted for 10 min. RESULTS: The extract caused a significant dose-dependent reduction in serum glucose levels in mice, when administered at doses of 50, 100, 200 and 400 mg/kg body weight as compared to the control animals (P<0.05). The highest reduction of serum glucose (60.5%) was observed at a dose of 400 mg/kg. In comparison, a standard antihyperglycemic drug glibenclamide, when administered at a dose of 10 mg/kg body weight, lowered serum glucose levels by 48.6%. The extract also demonstrated a significant dose dependent antinociceptive activity compared to control animals (P<0.05). At a dose of 400 mg/kg body weight, the number of abdominal writhings was inhibited by 40.9% as compared to 49.0% inhibition obtained with a standard antinociceptive drug aspirin, administered at a dose of 200 mg/kg body weight. CONCLUSION: The significant antihyperglycemic and antinociceptive activities demonstrated by the extract validate the use of E. thymifolia in folk medicine of Bangladesh for treatment of diabetes and pain, and merit further scientific studies leading to discovery of efficacious drugs. PMID- 22313891 TI - Comparative study on WHO Western Pacific Region and World Federation of Chinese Medicine Societies international standard terminologies on traditional medicine: defense, qi, nutrient and blood pattern identification/syndrome differentiation (part 2). PMID- 22313892 TI - Lifestyle and late life cognitive health: sufficient evidence to act now? PMID- 22313893 TI - Regulation of the expression of interleukin-8 induced by 25-hydroxycholesterol in retinal pigment epithelium cells. AB - PURPOSE: This study aimed at elucidating the molecular mechanisms involved in the regulation of IL-8 production by several oxysterols in retinal pigment epithelium (RPE) cells. METHODS: A human cell line from RPE (ARPE-19) was used to test the role of cholesterol and several oxysterols (25-OH, 7-KC and 7beta-OH) in the expression and secretion of IL-8. Expression of IL-8 was assessed by real-time PCR, while IL-8 secretion was evaluated by ELISA. PI3K-, MEK1/2-, ERK1/2- and NF kappaB-specific inhibitors were used to assess the specific role of the several players on the regulation of IL-8 production by oxysterols. A gene-reporter assay for AP-1 activity was also conducted to evaluate the putative role of this transcription factor on IL-8 expression induced by oxysterols. RESULTS: Here, we demonstrate that 25-OH specifically increases transcription and secretion of the cytokine IL-8 in ARPE-19 cells. Indeed, treatment of ARPE-19 with 25-OH, but not with 7-KC, 7beta-OH or cholesterol, induced the secretion of IL-8 from cells. 25 OH also induced the activation/phosphorylation of ERK1/2 through a mechanism dependent on MEK, ERK1/2 and PI3K kinase activity. Real-time PCR and ELISA experiments demonstrated that 25-OH increased transcription and secretion of IL-8 through a mechanism that is dependent on ERK1/2 and PI3K activity. Furthermore, 25-OH triggered the activation/phosphorylation of the AP-1 component c-Jun and, consistently, increased the transcriptional activity of AP-1. Additionally, we also found that 25-OH decreases the levels of IkappaB and increases the nuclear levels of NF-kappaB p65 subunit and that inhibition of NF-kappaB activity partially prevents the increased secretion of IL-8 induced by 25-OH. CONCLUSIONS: The results presented in this study suggest a role for 25-OH in inducing IL-8 production through pathways that are likely to involve AP-1 and NF-kappaB in ARPE 19 cells. Our data may also provide new molecular targets for the treatment of AMD. PMID- 22313894 TI - Evidence versus standard versus best practice: show me the data! PMID- 22313896 TI - A 21-year-old white woman diagnosed with cerebral venous sinus thrombosis related to oral contraceptive and Factor V Leiden. AB - Empirical research has established the fact that the use of oral contraceptives in young women with the Factor V Leiden mutation increases the relative risk of cerebral venous sinus thrombosis. Cerebral venous sinus thrombosis is a rare cerebral vascular injury whose ambiguous presentation contributes to delayed and often-inaccurate diagnosis. This case report presents a 21-year-old White woman with a severe headache who presented to the emergency department and was diagnosed with cerebral venous sinus thrombosis. The purpose of this article is to educate advanced practice emergency care nurses on the importance of understanding genetic and acquired risk factors in diagnosing cerebral venous sinus thrombosis. A genetic risk assessment tool is introduced that advanced practice nurses may incorporate into their routine assessments to evaluate the likelihood of a genetic predisposition for illness, such as shown in this case study. PMID- 22313895 TI - Adverse drug events in the emergency department: why genetics matters in practice. AB - A recent clinical research study with a case study approach is used to illustrate the importance of translational research in the role of the advanced practice nurse. The case study module used in this column is "Adverse Drug Events in the Emergency Department: Why Genetics Matters in Practice." The study results showed that patients taking multiple drugs metabolized through the cytochrome P450 enzyme system had a higher prevalence of drug-drug exposure. These drug-drug exposures may lead to potentially serious drug-drug interactions. The implications and clinical relevance of these findings for advance practice nurses are discussed. PMID- 22313897 TI - Review of vasopressor therapy in the setting of vasodilatory shock. AB - Appropriate selection and utilization of vasopressor therapy are important in the treatment of vasodilatory shock, because inappropriate use can result in increased morbidity and mortality. Vasopressors are differentiated on the basis of their receptor activity, as well as their pharmacokinetic and pharmacodynamic properties. Understanding the pathophysiology of receptor responses in shock, dose-dependent receptor activity variations, and unique patient-specific factors that alter response, all assist the health care provider in selecting the appropriate agent for each patient. Treatment is further individualized on the basis of clinical response and medication titration, as well as laboratory value changes. The intent of this review is to discuss relevant management issues associated with vasopressor use in the emergency department. PMID- 22313898 TI - An 8-year-old with tinea capitis and secondary rash. AB - Patients often utilize the emergency department as a provider of primary care or as an avenue to obtain a "second opinion." Rashes are a common chief complaint in the emergency department and can often be the most puzzling for practitioners to diagnose. Atypical presentations, variations, and secondary lesions can be especially challenging. The emergency practitioner must perform a thorough history and physical, including current treatment for preexisting skin conditions. While the majority of patients with a rash who present to the emergency department have only a minor condition, a reported phenomenon associated with dermatitis is a dermatophytid reaction. The ability to recognize this phenomenon is crucial as misdiagnosing can have lasting consequences. PMID- 22313899 TI - Body surface mapping improves diagnosis of acute myocardial infarction in the emergency department. AB - Traditionally, the diagnosis of acute myocardial infarction (AMI) in emergency departments is done through an assessment of history and presenting symptoms, 12 lead electrocardiogram (ECG), and cardiac biomarkers. The 12-lead ECG is not highly sensitive for detecting ECG changes, and some infarctions may be missed. Failure to identify patients in the early stages of AMI can result in failure to provide beneficial therapies. New technology, the 80-lead ECG, uses body surface mapping to provide a more comprehensive view of cardiac electrical activity. Body surface mapping has greater sensitivity in detecting AMI in the inferoposterior portions of the left ventricle and the right ventricle. Portable hardware and user-friendly software coupled with an easily applied disposable torso vest containing the electrodes produce a 12-lead ECG, 80-lead ECG, and color contour torso or flat map showing ECG changes. Recent studies support the use of 80-lead body surface mapping for detecting AMI in the emergency department. PMID- 22313901 TI - Toxicology in the emergency department: a review for the advanced practice nurse. AB - General assessment, resuscitation strategies, and risk assessment of the poisoned patient are explored in this article, including specific interventions for unresponsive patients and seizures. Sympathomimetic and anticholinergic toxidromes are described in terms of clinical presentation and treatment strategies and are compared with other common toxidromes. Controversies in gastric decontamination are also outlined, including consensus panel and national organizational recommendations. Despite available methods for toxin elimination, advances in medicine, and pharmacotherapy options, the cornerstone of toxicology remains supportive care. The purpose of this article is to equip the advanced practice nurse in the emergency setting with baseline knowledge to provide initial care of the poisoned patient. PMID- 22313902 TI - Application of the emergency department census model. AB - As health care systems across the United States continue to grapple with emergency department (ED) crowding and identify mechanisms to improve ED throughput, quantification of intradepartmental efficiency and workload is required to provide much-needed objective measures to assist in the continuing development, implementation, and evaluation of these strategic initiatives. In an attempt to establish a straightforward measure of ED efficiency in relation to daily census and ED crowding, T. J. Flottemesch (2006) developed the ED Census Model. The purpose of this study was to apply the ED Census Model in a Southwestern U.S. community hospital setting. This application of the ED Census Model yielded 3 components: the ED Census Component, the ED Throughput Component, and the ED Efficiency Threshold Component. The components provide information necessary for understanding the impact of patient arrivals and departures on the underlying workflow processes that determine throughput. PMID- 22313903 TI - The effectiveness of a provider in triage in the emergency department: a quality improvement initiative to improve patient flow. AB - Hospital emergency departments (EDs) throughout the United States are faced with overwhelming challenges due to the high demand for services, an increasing number of visits, overuse and misuse of services, and escalating healthcare costs. The result of this situation is that EDs are overcrowded, patients are experiencing long wait times, ambulances are being diverted, admitted patients are being boarded, and patients in need of emergency medical care are leaving without treatment. The purpose of this article is to present a quality improvement initiative designed and implemented to improve patient flow through an ED by redesigning the triage process to increase the efficiency and timeliness of initial patient contact with a licensed medical provider, increasing patient satisfaction, and decreasing the number of patients who leave without being seen. To accomplish these goals, a nurse practitioner/physician assistant medical provider was reallocated to the triage area to perform an initial assessment and initiate diagnostic studies. The results of this initiative have proven to be positive in goal attainment. The time from patient arrival to initial contact with a licensed medical provider has decreased from 75 to 25 min. The percentage of patients who leave without being seen has decreased from 3.6% to 0.9%. PMID- 22313904 TI - Hypothermia in the trauma patient: how vital is this sign? AB - Recognizing the adverse impact that trauma has on a patient's overall well-being and hemodynamic stability is key to successful management and improved outcomes for this patient population. It is well established that trauma is accompanied by deadly pathophysiological sequelae, referred to as the "trauma triad." This triad is characterized by hypothermia, acidosis, and coagulopathy. This triad is cyclic and, moreover, each element of the triad builds upon one another to exacerbate the next. Hence, evidence demonstrates that it is important to recognize the cycle and intervene early to reduce or prevent negative outcomes. PMID- 22313905 TI - Sexual assault injuries and increased risk of HIV transmission. AB - Sexual assault and HIV are coexisting public health problems. Sexual assault may increase HIV transmission risk through diverse mechanisms, such as infliction of anal, oral, and genital injuries by penile, digital, or object penetration, extragenital trauma, concurrent sexually transmitted infections, condom use, and whether the perpetrator was circumcised. PMID- 22313906 TI - Research capacity development in South African manganese mines to bridge exposure and neuropathologic outcomes. AB - Manganese (Mn) is a common occupational exposure worldwide. Recent studies indicate clinical and imaging evidence of neurotoxicity in chronically exposed workers. The pathologic significance of these findings is unclear. South Africa produces over 80% of the world's Mn from mines from a desert region in the Northern Cape Province. An autopsy program at the National Institute for Occupational Health (NIOH) in South Africa has provided compensation to families for mining-related lung diseases for almost 100 years. Building on this, we implemented a brain autopsy program to investigate the feasibility of obtaining brains from South African Mn miners and non-exposed reference miners to investigate neuropathologic consequences of chronic Mn exposure. Employing an experienced occupational health nurse, we identified deceased miners within 100 square km of the Mn mines. The nurse was notified of any Mn (case) or other (reference) miner or ex-miner death by local medical practitioners, occupational health and mine physicians, and community members, and families were approached for consent to remove the brains in addition to the cardio-respiratory organs. Families of deceased miners who had an autopsy at the NIOH in Johannesburg were also approached. To confirm exposure in Mn miners, mean pallidal indices were compared between Mn miners and non-exposed reference miners. Sixty-eight potential brain donors were identified; we obtained consent from the families to remove 51 (75%). The mean autopsy interval was seven days. With optimized fixation methods, the tissue quality of the brains for gross and regular microscopic examination was excellent. Ex vivo MRI demonstrated increased pallidal index in Mn miners compared to reference miners. We conclude that obtaining brain tissue from deceased miners in South Africa is highly successful with only a modest investment in local infrastructure. Tissue quality was excellent and should be ideal to investigate the neuropathologic consequences of chronic occupational Mn exposure. PMID- 22313907 TI - Preparation of alpha-mannoside hydrogel and electrical detection of saccharide protein interactions using the smart gel-modified gate field effect transistor. AB - The purpose of this study was to detect saccharide-protein interaction capitalizing on the gel-modified field effect transistor [FET]. A lectin sensitive polymer gel that undergoes volume changes in response to the formation of molecular complex between 'pendant' carbohydrate and a 'target' lectin concanavalin A [Con A] was synthesized. It was revealed that direction and magnitude of the gel response (swelling or deswelling) could be readily designed depending on composition and network density of the gel. The Con A-sensitive polymer gel has shown the ability to transduce the detection of saccharide protein interactions into electrical signals for FET.PACS: 87.85.jf, bio-based materials. PMID- 22313909 TI - Make no mistake(s). PMID- 22313908 TI - Peripheral T-lymphocytes express WNT7A and its restoration in leukemia-derived lymphoblasts inhibits cell proliferation. AB - BACKGROUND: WNT7a, a member of the Wnt ligand family implicated in several developmental processes, has also been reported to be dysregulated in some types of tumors; however, its function and implication in oncogenesis is poorly understood. Moreover, the expression of this gene and the role that it plays in the biology of blood cells remains unclear. In addition to determining the expression of the WNT7A gene in blood cells, in leukemia-derived cell lines, and in samples of patients with leukemia, the aim of this study was to seek the effect of this gene in proliferation. METHODS: We analyzed peripheral blood mononuclear cells, sorted CD3 and CD19 cells, four leukemia-derived cell lines, and blood samples from 14 patients with Acute lymphoblastic leukemia (ALL), and 19 clinically healthy subjects. Reverse transcription followed by quantitative Real-time Polymerase chain reaction (qRT-PCR) analysis were performed to determine relative WNT7A expression. Restoration of WNT7a was done employing a lentiviral system and by using a recombinant human protein. Cell proliferation was measured by addition of WST-1 to cell cultures. RESULTS: WNT7a is mainly produced by CD3 T-lymphocytes, its expression decreases upon activation, and it is severely reduced in leukemia-derived cell lines, as well as in the blood samples of patients with ALL when compared with healthy controls (p <=0.001). By restoring WNT7A expression in leukemia-derived cells, we were able to demonstrate that WNT7a inhibits cell growth. A similar effect was observed when a recombinant human WNT7a protein was used. Interestingly, restoration of WNT7A expression in Jurkat cells did not activate the canonical Wnt/beta-catenin pathway. CONCLUSIONS: To our knowledge, this is the first report evidencing quantitatively decreased WNT7A levels in leukemia-derived cells and that WNT7A restoration in T lymphocytes inhibits cell proliferation. In addition, our results also support the possible function of WNT7A as a tumor suppressor gene as well as a therapeutic tool. PMID- 22313910 TI - Bevacizumab (Avastin): An anti-angiogenic drug associated with osteonecrosis of the jaw. PMID- 22313911 TI - Clinical tips for porcelain veneer cases with enamel hypocalcification. PMID- 22313912 TI - Latest innovations in air and electric handpieces. PMID- 22313913 TI - Finishing and polishing criteria for minimally invasive composite restorations. AB - To achieve the benefits that composite restorations can provide, it is incumbent on dentists to understand the importance of proper finishing and polishing techniques and how to incorporate them appropriately into everyday practice. A smooth surface finish is clinically necessary because the presence of surface irregularities from poor finishing and polishing can lead to staining, plaque retention, gingival irritation, recurrent caries, abrasiveness, wear kinetics, and tactile perception by the patient. However, finishing and polishing procedures for direct composite restorations are technique- and material sensitive. This article describes the proper composite material placement considerations, as well as finishing and polishing techniques and materials, for providing highly esthetic, long-lasting restorations. By incorporating such protocol into their everyday practices, dentists can increase the long-term esthetic and plaque-resistant predictability of direct composite restorations. PMID- 22313914 TI - 3 mm can save your case: Making beauty function. AB - Understanding esthetic design is not enough if restorations are to withstand the forces of function. Dentists also must understand the relationships of incisal tables, the interincisal angle, disclusion forces, and the implications of changing those parameters when restoring the anterior dentition. While canine protected occlusion is often a goal, it may not always be appropriate or attainable. This article describes the details of creating a functional anterior design that will not only be beautiful but will have the best chance of withstanding parafunctional activity and abnormal force. PMID- 22313915 TI - Maximizing esthetic results on zirconia-based restorations. AB - With a flexural strength of approximately 900-1,100 MPa, zirconium oxide is one of the toughest all-ceramic materials available in dentistry.1 It can be used to fabricate both single-unit and long-span bridge frameworks. A moderate level of translucency makes it suitable for esthetically demanding clinical cases, such as restoring maxillary anterior teeth. A variety of well-designed porcelain veneering systems allow technicians to apply their artistic skills to create natural, lifelike restorations. A good balance of strength, precision, and translucency allows zirconia-based restorations to accommodate a variety of clinical situations. PMID- 22313916 TI - Successful strategies for matching one or two indirect restorations to natural dentition. AB - One of the most difficult and noble undertakings of a dental restorative team is to provide an indirect restoration for a compromised tooth surrounded by otherwise healthy, natural dentition. Matching one or two indirect dental restorations to adjacent healthy teeth is a herculean task for both the dentist and laboratory technician. The team must be knowledgeable of the natural dentition's characteristics to best mimic and recreate those same characteristics in a man-made restoration. Knowledge of principles in smile design, dental anatomy, color, characterization, material selection, doctor-technician communication, and clinical acumen are necessary to achieve a successful outcome when matching one or two indirect restorations to natural dentition. PMID- 22313917 TI - Oral involvement of chronic graft-versus-host disease in hematopoietic stem cell transplant recipients. AB - Oral manifestations are common in patients who are diagnosed with chronic graft versus-host-disease (cGVHD). These manifestations can present as oral mucosal lesions, salivary gland dysfunction, or reduction of the mouth opening due to cutaneous sclerosis. Although several studies have reported the prevalence of oral involvement in cGVHD, few have reported details of different types and severity of oral lesions of cGVHD, according to the NIH. Furthermore, the authors are aware of only one published study concerning oral manifestations of cGVHD in Brazil. The purpose of this study was to evaluate the prevalence and severity of oral involvement of cGVHD. Oral evaluation of hematopoietic stem cell transplant (HSCT) recipients was conducted on 22 patients (12 men and 10 women) from December 2007 to May 2009. The following categories were assessed: Age, gender, underlying disease, time postHSCT, history of GVHD, therapy for GVHD, oral lesions, xerostomia, resting salivary flow rate, and mouth opening. Oral lesions were classified according to NIH criteria, and the results were submitted to a descriptive analysis. According to the NIH, patients presented diagnostic (40.9%), distinctive (31.9%), and common (9.1%) features of oral cGVHD. Oral involvement of cGVHD was identified in 81.8% of patients, 68.2% as mucosal lesions and 59.1% as salivary gland dysfunction. Reduced mouth opening was observed in 12 patients (80%), with one case associated with cutaneous sclerosis. Oral involvement was frequent in these patients; for many, it was the first clinical manifestation of cGVHD. PMID- 22313918 TI - Effects of a paste-free prophylaxis polishing cup and various prophylaxis polishing pastes on tooth enamel and restorative materials. AB - The application of cleaning and polishing agents to a patient's dentition is a routine part of many dental practices. This study measured the surface roughness and surface gloss of tooth enamel, composite resin, and dental porcelain restorative materials when exposed to a paste-free prophylaxis polishing cup as well as a conventional prophylaxis polishing paste. Samples of human tooth enamel, a composite resin restorative material, and dental porcelain were prepared by a series of polishing papers to produce a flat smooth surface. The baseline average surface roughness (Ra) was measured using a contact stylus profilometer, and the surface gloss was measured with a glossmeter. The test samples were subjected to a standardized polishing routine using a paste-free prophylaxis polishing cup and a fine- or coarse-particle prophylaxis paste. Post treatment surface roughness and gloss measurements were compared using a paired t statistical test. The conventional prophylaxis pastes increased surface roughness and decreased the gloss of the composite resin and tooth enamel test groups. The paste-free cups did not significantly affect the surface roughness of the enamel or the restorative materials. Dental porcelain surface roughness essentially was not affected by the application of paste-free cups and the fine and coarse pastes. PMID- 22313919 TI - Correlation of awareness and practice of working postures with prevalence of musculoskeletal disorders among dental professionals. AB - Over the last 20 years, a great many innovations have been introduced that are designed to reduce laborious activities; however, an unexpected consequence of these developments is a trend toward a sedentary lifestyle and prolonged static postures that are accompanied by musculoskeletal disorders (MSDs). MSDs have become a major issue of concern because the afflictions can be severe enough to disable professional careers. Although clinical dentistry is a field with immense potential for MSDs, only a few studies have investigated this issue. The present study was carried out addressing prevalence and awareness level of MSDs among 500 dental professionals from Central India. Also, the interrelationship between practices of working postures with occurrence of pain in different body parts were assessed using a structured questionnaire format. The results were statistically significant, and indicated that the prevalence of MSDs is high and that there is a dire need to enhance awareness regarding correct working postures. This study encompassed all factors that can be addressed as causes for MSDs among dentists. PMID- 22313920 TI - The role of volume of multi-surface restorations in posterior teeth: Treatment options. AB - Teeth containing large defective restorations are frequently indicated to receive crowns to prevent catastrophic fracture. There is a considerable lack of consensus as to when the size of an existing restoration needing retreatment is sufficiently large to warrant a crown. In addition, the treating dentist's gender, age, and location also have been found to influence this decision. An in vitro method was developed to estimate a restoration's volume proportion (VP). This study validates and investigates correlations between the restoration's VP, the decision to indicate a crown, and the responding dentist's demographic information. The coronal portions of occlusal view and bitewing radiographic images of restored posterior teeth were traced to yield four surface areas used in estimating the restoration's VP. An online survey of 15 patients, including intraoral and radiographic images of defective restorations, was created. Dentists were invited to select treatment for each patient's tooth, with options including replacing the restoration only or indicating a crown. Analysis was accomplished using repeated-measures logistic regression. Of the 300 respondents, 17% were female and 14% were from outside the U.S. The relationship between a responding dentist indicating a crown and the restoration's VP, the tooth type (molar or premolar), and nationality (U.S. or foreign dentist) were all deemed statistically significant. Crowns were indicated for molars significantly more often than for premolars, with a significant VP interaction. The final model of tooth, VP, nationality, and the interaction of tooth and VP was used to generate mean predicted proportions for indicating a crown. PMID- 22313921 TI - Head and neck cancer in two American presidents: Case reports. AB - Two former U.S. presidents, Ulysses S. Grant and Grover Cleveland, were diagnosed with head and neck cancer in 1884 and 1893, respectively. A historical review of the risk factors, diagnoses, and treatments is examined and compared with modern day interpretations. A comparison was made using the original diagnoses with today's equivalent diagnosis. Different treatment outcomes at the time of the original diagnoses relative to today's treatment are reviewed. Clinicians must be familiar with risk factors, signs, symptoms, diagnosis, and treatment of head and neck cancer. PMID- 22313922 TI - Evaluation of four cementation strategies on the push-out bond strength between fiber post and root dentin. AB - This trial used push-out testing to evaluate four different fiber post cementation strategies. Specimens of bovine mandibular teeth were randomly allocated into four groups according to cementation strategies (n = 10): ScotchBond MultiPurpose and RelyX ARC (Group 1); AdheSE and Multilink Automix (Group 2); phosphoric acid and RelyX U100 (Group 3); and RelyX U100 (Group 4). Four slices from each specimen (2.0 mm thick) were obtained for the push-out test. All slices were analyzed for failure mode after testing. A one-way ANOVA showed differences between the groups (P = 0.002). A Tukey test indicated that Group 1 had the highest bond strength values (13.96 +/- 6.41 MPa). Groups 2 (6.58 +/- 2.14 MPa), 3 (5.85 +/- 2.57 MPa), and 4 (8.19 +/- 2.28 MPa) had similar bond strengths, but all of them were lower than Group 1. A three-step total etching adhesive system, associated with a conventional resin cement, might be a good alternative for fiber post cementation. PMID- 22313923 TI - Intraoral chemical burn from use of 3% hydrogen peroxide. AB - Injudicious use of over-the-counter 3% hydrogen peroxide, a relatively potent oxidative agent, can result in a chemical burn to the oral mucosa. This article describes a patient who rinsed with 3% hydrogen peroxide for periods of more than two minutes as a self-prescribed remedy for oral discomfort following seafood ingestion. Subsequently, the patient experienced pain and extensive chemical burns of the sublingual and buccal mucosa and gingiva. In addition, the buccal mucosa underwent necrosis. Prolonged oral mucosal contact with 3% hydrogen peroxide is ill-advised. PMID- 22313924 TI - Isolated gingival enlargement. Neurofibroma. PMID- 22313925 TI - Postoperative lip swelling. Angioedema related to an ACE inhibitor. PMID- 22313926 TI - Diametral tensile strength of four composite resin core materials with and without centered fiber dowels. AB - This study evaluated the diametral tensile strength of composite resin core materials with and without fiber dowels. Eight groups were established (n = 20), four with composite resins and four with fiber dowels. Samples were tested using a universal testing machine and evaluated using scanning electron microscopy. One way ANOVA and a Tukey B-rank order test (P = 0.05) indicated that the tensile values of two of the four composite resins decreased significantly when their matching fiber dowels were introduced. PMID- 22313927 TI - Sodium hypochlorite, chlorhexidine gluconate, and commercial denture cleansers as disinfecting agents against Candida albicans: An in vitro comparison study. AB - When treating patients who have candidiasis, removable dental appliances in active use should be treated as well. The authors aimed to determine, in vitro, the lowest concentration of sodium hypochlorite that would eliminate Candida albicans biofilm, as well as the effectiveness of additional products against C. albicans. Strains of C. albicans formed biofilms on microtiter plates. Sodium hypochlorite was added in dilutions (1:1 to 1:512) and Peridex was added in concentrations of 25%, 50%, and 100%. The plates were incubated for 30 minutes. One tablet each of Efferdent, Polident for Partials, and Polident for Dentures was dissolved in 200 mL of sterile water and added to additional groups of plates. One group was incubated for 30 minutes; the other was incubated for 18 hours. An XTT spectrophotometric reduction assay measured biofilm metabolic activity. Biofilm activity decreased 100% for all strains exposed to sodium hypochlorite for 30 minutes in concentrations of 1:32 or stronger. Biofilm activity decreased 100% for most strains when treated with 50% or 100% Peridex for 30 minutes and Polident for Dentures for 18 hours. From these results, it appears appropriate for providers to recommend a solution of two teaspoons of sodium hypochlorite in one cup of water (1:25) for 30 minutes to treat dentures contaminated with C. albicans. PMID- 22313928 TI - Diagnosis and treatment of dry mouth. AB - For effective management of dry mouth, early diagnosis and aggressive, symptom based treatment are necessary to help alleviate much of the discomfort and to retard progression of the disorder. Many effective strategies are available to help patients manage their symptoms. Routine follow-up care with physicians and dentists is essential. With early intervention and proper individualized care, people with dry mouth should be able to lead full and comfortable lives. PMID- 22313929 TI - The influence of different placement techniques on the microtensile bond strength of low-shrink silorane composite bonded to Class I cavities. AB - The aim of this in vitro study was to evaluate the microtensile bond strength (uTBS) of a low-shrink silorane-based composite (Filtek Silorane) and a methacrylate-based composite (Filtek Z250) to the bottom dentin of a Class I cavity using different placement techniques. Twelve third molars were used. Standard, box-type Class I cavities (6.0 x 4.0 x 2.5 mm) were prepared at the occlusal crown center, with the pulpal floor ending approximately at the midcoronal dentin. The teeth were then randomly divided into four groups, according to each placement technique: ZI--Filtek Z250 placed incrementally; ZB- Filtek Z250 placed in bulk; SI--Filtek Silorane placed incrementally; and SB- Filtek Silorane placed in bulk. Each restored third molar was subjected to microtensile bond testing after 24 hours of storage in distilled water at 37 degrees C. After storage, each molar was longitudinally sectioned in both axes to obtain rectangular sticks with an approximate 0.49 mm2 cross-sectional area. Data were analyzed by one-way ANOVA followed by a Tukey post hoc test (P = 0.05). After debonding, the failure modes were analyzed using a stereomicroscope. The ZI group (72.6 MPa) showed the highest uTBS, followed by the ZB group (60.2 MPa), while the SI (34.4 MPa) and SB (42.6 MPa) groups demonstrated statistically significant lower bond strengths. The type of placement technique did not influence the uTBS of silorane-based composites to the bottom dentin of Class I cavities. The methacrylate-based composite showed superior performance, regardless of the placement technique. PMID- 22313930 TI - Treatment of gingival recession in two surgical stages: Free gingival graft and connective tissue grafting. AB - This report describes a clinical case of severe Miller Class II gingival recession treated by two stages of surgery that combined a free gingival graft and connective tissue grafting. First, a free gingival graft (FGG) was performed to obtain an adequate keratinized tissue level. Three months later, a connective tissue graft (CTG) was performed to obtain root coverage. The results indicated that the FGG allows for a gain in the keratinized tissue level and the CTG allows for root coverage with decreased recession level after 16 months. Therefore, for this type of specific gingival recession, the combination of FGG and CTG can be used. PMID- 22313931 TI - Hybrid layer thickness and morphology: Influence of cavity preparation with air abrasion. AB - Dentinal surfaces prepared with air abrasion have considerably different characteristics from those prepared with conventional instruments. Different hybrid layer morphology and thickness occur, which can result in differences in the quality of restorations placed on dentinal surfaces prepared with a diamond bur compared to surfaces prepared using air abrasion. The objective of this study was to compare the hybrid layer thickness and morphology formed utilizing Scotchbond Multi-Purpose Plus (SBMP) on dentin prepared with a diamond bur in a high-speed handpiece and on dentin prepared using air abrasion. Flat dentin surfaces obtained from five human teeth were prepared using each method, then treated with the dentin adhesive system according to manufacturer's instructions. After a layer of composite was applied, specimens were sectioned, flattened, polished, and prepared for scanning electron microscopy. Ten different measurements of hybrid layer thickness were obtained along the bonded surface in each specimen. SBMP produced a 3.43 +/- 0.75 um hybrid layer in dentin prepared with diamond bur. This hybrid layer was regular and found consistently. In the air abrasion group, SBMP produced a 4.94 +/- 1.28 um hybrid layer, which was regular and found consistently. Statistical ANOVA (P = 0.05) indicated that there was a statistically significant difference between the groups. These data indicate that the air abrasion, within the parameters used in this study, provides a thick hybrid layer formation. PMID- 22313932 TI - Severe oligodontia and dental anomalies in a child with a history of multiple natal teeth: An eight-year retrospective. AB - This article reports the case of a boy born with 11 natal teeth who had many alterations in his permanent dentition. In this case, 22 teeth were missing and a shape anomaly was detected in eight teeth. The treatment consisted of prosthetic rehabilitation and follow-up of teeth eruption and jaw growth. PMID- 22313933 TI - An examination of the dynamic changes in prostate-specific antigen occurring in a population-based cohort of men over time. AB - OBJECTIVE: * To determine whether prostate-specific antigen velocity (PSA-V), PSA doubling time (PSA-DT), or PSA percentage change (PSA-PC) add incremental information to PSA alone for community-based men undergoing prostate cancer (PCa) screening. PARTICIPANTS AND METHODS: * A population-based cohort of 11 872 men from Olmsted County, MN undergoing PSA screening for PCa from 1993 to 2005 was analysed for PSA, PSA-DT, PSA-PC and PSA-V and subsequent PCa. * Receiver operating characteristics curves and logistic regression were used to calculate the area under the curve (AUC) and Aikaike's information criterion. * Reclassification analysis was performed and the net reclassification improvement and integrated discrimination improvement were measured. * The method of Begg and Greenes was used to adjust for verification bias. RESULTS: * The single best predictor of future PCa was PSA (AUC = 0.773) with PSA-V (AUC = 0.729) and PSA DT/PSA-PC (AUC = 0.689) performing worse. * After age adjustment, combining PSA with PSA-V (AUC = 0.773) or PSA-DT/PSA-PC (AUC = 0.773) resulted in no better predictions than PSA alone. * Reclassification analysis showed that adding PSA-V or PSA-DT/PSA-PC to PSA did not result in a meaningful amount of reclassification. CONCLUSIONS: * PSA is a better predictor of future PCa than PSA V, PSA-DT, or PSA-PC. * Adding PSA-V, PSA-DT, or PSA-PC to PSA does not result in clinically relevant improvements in the ability to predict future PCa. PMID- 22313934 TI - Comparison of clinical efficacy and safety between denosumab and alendronate in postmenopausal women with osteoporosis: a meta-analysis. AB - The aim of this study was to perform a head-to-head comparison of efficacy and safety profile between 60 mg denosumab (Den) subcutaneously (SC) per 6 months (Q6M) and 70 mg alendronate (Aln) orally per week (QW) for postmenopausal women with low bone mineral density. We searched electronic databases comparing efficacy and safety of Den SC Q6M and Aln QW in postmenopausal women. The primary outcomes of efficacy evaluation in included trials were incidence of clinical fracture in both groups and bone mineral density (BMD) at different skeletal sites. And adverse events (AEs), including incidence of neoplasms and infections, were considered as secondary outcomes. Following the instructions of 'Cochrane Handbook for systematic Reviews of Interventions 5.0.2', we identified eligible studies, evaluated the methodological quality and abstracted relevant data. Four heterogeneous randomised controlled trials (RCTs) involving 1942 women were identified. The results of review showed low evidence quality that supported the hypothesis the denosumab vs. alendronate could reduce risk of fracture [OR (95% CI) 1.42 (0.84 to 2.40), 11 more women per 1000 (from 4 fewer to 36 more), p = 0.19] but the moderate to high quality evidence suggesting treatment with 60 mg Den SC Q6M was more effective for postmenopausal women in increasing BMD [at distal radius (DR), total hip (TH), lumbar spine (LS), and femoral neck (FN)]. Hazards of neoplasms [OR (95% CI) 1.10 (0.65 to 1.86), 3 more per 1000 (from 10 fewer to 24 more), p = 0.62] or infections [OR (95% CI) 0.95 (0.79 to 1.15), 12 fewer per 1000 (from 53 fewer to 33 more,), p = 0.62] were appeared to be similar.Our review suggested within 1 year 60 mg Den SC Q6M treatment was more effective in increasing bone mass but could not reduce the fracture risk to a greater extent than 70 mg Aln QW therapy. Also the Den SC Q6M therapy did not increase the risks of neoplasms and infections compared with Aln QW. PMID- 22313935 TI - Clustering of HIV-1 Subtypes Based on gp120 V3 Loop electrostatic properties. AB - BACKGROUND: The V3 loop of the glycoprotein gp120 of HIV-1 plays an important role in viral entry into cells by utilizing as coreceptor CCR5 or CXCR4, and is implicated in the phenotypic tropisms of HIV viruses. It has been hypothesized that the interaction between the V3 loop and CCR5 or CXCR4 is mediated by electrostatics. We have performed hierarchical clustering analysis of the spatial distributions of electrostatic potentials and charges of V3 loop structures containing consensus sequences of HIV-1 subtypes. RESULTS: Although the majority of consensus sequences have a net charge of +3, the spatial distribution of their electrostatic potentials and charges may be a discriminating factor for binding and infectivity. This is demonstrated by the formation of several small subclusters, within major clusters, which indicates common origin but distinct spatial details of electrostatic properties. Some of this information may be present, in a coarse manner, in clustering of sequences, but the spatial details are largely lost. We show the effect of ionic strength on clustering of electrostatic potentials, information that is not present in clustering of charges or sequences. We also make correlations between clustering of electrostatic potentials and net charge, coreceptor selectivity, global prevalence, and geographic distribution. Finally, we interpret coreceptor selectivity based on the N6X7T8|S8X9 sequence glycosylation motif, the specific positive charge location according to the 11/24/25 rule, and the overall charge and electrostatic potential distribution. CONCLUSIONS: We propose that in addition to the sequence and the net charge of the V3 loop of each subtype, the spatial distributions of electrostatic potentials and charges may also be important factors for receptor recognition and binding and subsequent viral entry into cells. This implies that the overall electrostatic potential is responsible for long-range recognition of the V3 loop with coreceptors CCR5/CXCR4, whereas the charge distribution contributes to the specific short-range interactions responsible for the formation of the bound complex. We also propose a scheme for coreceptor selectivity based on the sequence glycosylation motif, the 11/24/25 rule, and net charge. PMID- 22313936 TI - Effects of neonatal enteral glutamine supplementation on cognitive, motor and behavioural outcomes in very preterm and/or very low birth weight children at school age. AB - In very preterm ( < 32 weeks of gestation) and/or very low birth weight (VLBW, < 1500 g birth weight) children, serious neonatal infections are among the main causes of poor developmental outcomes later in childhood. The amino acid glutamine has been shown to reduce the incidence of serious neonatal infections in very preterm and/or VLBW children, while developmental effects beyond 24 months are unknown. We determined the cognitive, motor and behavioural outcomes at school age of a cohort of sixty-four very preterm and/or VLBW children (aged 7.5 (sd 0.4) years) who participated in a randomised placebo-controlled trial using enteral glutamine between day 3 and day 30 of life. Cognitive and motor outcomes were studied using the Wechsler Intelligence Scale for Children-III, the Movement Assessment Battery for Children (MABC), the Attention Network Test and a visual working memory task. Behavioural outcomes were evaluated using parent- and teacher-rated questionnaires. Intelligence quotient, processing speed, attentional functioning, working memory and parent- and teacher-rated behavioural outcomes were not different between children treated with glutamine or placebo; only visuomotor abilities as measured by the Ball Skills scale of the MABC (P = 0.002; d = 0.67) were poorer in the glutamine group. This effect persisted after taking into account the beneficial effects of lower serious neonatal infections rates in children treated with glutamine (P = 0.005). In conclusion, glutamine supplementation between day 3 and day 30 of life had neither beneficial nor detrimental effects on long-term cognitive, motor and behavioural outcomes of very preterm and/or VLBW children at school age, although visuomotor abilities were poorer in children that received glutamine. PMID- 22313938 TI - Biospecimens and biorepositories: from afterthought to science. AB - Biospecimens are recognized as critical components of biomedical research, from basic studies to clinical trials and epidemiologic investigations. Biorepositories have existed in various forms for more than 150 years, from early small collections in pathology laboratories to modern automated facilities managing millions of samples. As collaborative science has developed, it has been recognized that biospecimens must be of consistent quality. Recent years have seen a proliferation of best practices and the recognition of the field of "biospecimen science." The future of this field will depend on the development of more evidence-based practices in both the research and clinical settings. As the field matures, educating a new generation of biospecimen/biobanking scientists will be an important need. PMID- 22313939 TI - Sharing individual research results with biospecimen contributors: point. PMID- 22313940 TI - Sharing individual research results with biospecimen contributors: counterpoint. PMID- 22313941 TI - Light exposure and melatonin among rotating shift nurses--letter. PMID- 22313942 TI - The spontaneous resolution of heavy menstrual bleeding in the perimenopausal years. AB - OBJECTIVE: To obtain estimates of the rate of spontaneous resolution of heavy menstrual bleeding and to explore any association with specific menstrual symptoms. DESIGN: Two-year prospective cohort study. SETTING: Seven general practices, with 67 100 registered patients. POPULATION: All women aged 40-54 years on the practices age-sex registers. METHODS: Baseline postal questionnaire, with follow-up questionnaires sent to naturally menstruating respondents at 6, 12, 18 and 24 months. MAIN OUTCOME MEASURES: Rate of spontaneous resolution of heavy menstrual bleeding in naturally menstruating women. RESULTS: A total of 7121 baseline questionnaires were sent out, with an initial response rate of 63%. We recruited 2051 naturally menstruating women for the prospective cohort study. The spontaneous rate of resolution of heavy menstrual bleeding varied from 8.1% (95% CI 5.3-12%) in women aged 45-49 years, who had resolution without recurrence for 24 months, to 35% (95% CI 30-41%) in women aged 50-54 years, who had resolution without recurrence for 6 months. Rates were lower in those who reported interference with life from heavy menstrual bleeding. There was a strong association between the spontaneous resolution of heavy menstrual bleeding and skipped periods in women aged over 45 years. The association with 'cycle too variable to say' was significant, but weaker. CONCLUSION: There is a high prevalence, incidence and significant spontaneous rate of resolution of heavy menstrual bleeding in naturally menstruating women during the perimenopausal years. The rates have potential use for individual women, clinical decisions, devising and implementing interventions and planning the care of populations. PMID- 22313943 TI - Aggregation behavior of pyridinium based ionic liquids in water--surface tension, 1H NMR chemical shifts, SANS and SAXS measurements. AB - The aggregation behavior of short alkyl chain ionic liquids (ILs), namely 1 butyl, or 1-hexyl or 1-octylpyridinium and 1-octyl-2-, or -3-, or -4 methylpyridinium chlorides, in water has been assessed using surface tension, electrical conductance, (1)H NMR, small angle neutron scattering (SANS) and small angle X-ray scattering (SAXS) measurements. Critical aggregation concentrations (CACs), adsorption (at air/water interface) and thermodynamic parameters of aggregation have been reported. The values of CAC and area per adsorbed molecule decrease with the number of carbon atoms in the alkyl chain. The aggregation process is driven by both favorable enthalpy and entropy contributions. An attempt was made to examine the morphological features of the aggregates in water using SANS and SAXS methods. SANS and SAXS curves displayed diffuse structural peaks that could not be model fitted, and therefore, we calculated the mean aggregation numbers from the Q(max) assuming that IL molecules typically order into cubic type clusters. PMID- 22313945 TI - Chinese guidelines for the secondary prevention of ischemic stroke and transient ischemic attack 2010. PMID- 22313946 TI - Ocular and truncal lateropulsion associated with caudal lateral medullary infarction. PMID- 22313947 TI - Donepezil protects endothelial cells against hydrogen peroxide-induced cell injury. PMID- 22313948 TI - Associated factors of brachial-ankle pulse wave velocity in hypertensive patients aged 80 and over. PMID- 22313949 TI - Reprogramming to iPS cells and their subsequent hematopoietic differentiation is more efficient from MEFs than from preB cells. AB - Efficiencies of the generation of induced pluripotent stem (iPS) cells from either mouse embryonic fibroblasts (MEF) or from mouse fetal liver (FL) derived preB cells and their hematogenic potencies were compared. In 10 days approximately 2% of the MEFs transduced with Sox-2, Oct-4 and Klf-4 developed to iPS cells, while only 0.01% of transduced FL-preB cells yielded iPS cells, and only after around 3 weeks. Subsequently, the generated iPS cells were induced to differentiate into hematopoietic cells in vitro. On day 5 of differentiation MEF iPS yielded numbers and percentages of Flk-1(+) mesodermal-like cells comparable to those developed from embryonic stem (ES) cells. Compared to ES cells further differentiation to hematopoietic and lymphopoietic cells was reduced, possibly because of persistent expression of the reprogramming factors. By contrast, FL iPS cells developed lower numbers and percentages of Flk-1(+) cells, and no significant further development to hematopoietic or lymphopoietic cells could be induced. These results indicate that the efficiencies of iPS generation and subsequent hematopoietic development depends on the type of differentiated cell from which iPS cells are generated. PMID- 22313950 TI - Spectrum of gluten-related disorders: consensus on new nomenclature and classification. AB - A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years, key milestones have moved celiac disease from obscurity into the popular spotlight worldwide. Now we are observing another interesting phenomenon that is generating great confusion among health care professionals. The number of individuals embracing a gluten-free diet (GFD) appears much higher than the projected number of celiac disease patients, fueling a global market of gluten free products approaching $2.5 billion (US) in global sales in 2010. This trend is supported by the notion that, along with celiac disease, other conditions related to the ingestion of gluten have emerged as health care concerns. This review will summarize our current knowledge about the three main forms of gluten reactions: allergic (wheat allergy), autoimmune (celiac disease, dermatitis herpetiformis and gluten ataxia) and possibly immune-mediated (gluten sensitivity), and also outline pathogenic, clinical and epidemiological differences and propose new nomenclature and classifications. PMID- 22313952 TI - Evaluating HIV prevention effectiveness: the perfect as the enemy of the good. AB - There is a need to better understand the effectiveness of HIV-prevention programs. Cluster randomized designs have major limitations to evaluate such complex large-scale combination programs. To close the prevention evaluation gap, alternative evaluation designs are needed, but also better articulation of the program impact pathways and proper documentation of program implementation. Building a plausible case using mixed methods and modeling can provide a valid alternative to probability evidence. HIV prevention policies should not be limited to evidences from randomized designs only. PMID- 22313953 TI - Treatment outcomes of patients on second-line antiretroviral therapy in resource limited settings: a systematic review and meta-analysis. AB - BACKGROUND: A growing proportion of patients on antiretroviral therapy in resource-limited settings have switched to second-line regimens. We carried out a systematic review in order to summarize reported rates and reasons for virological failure among people on second-line therapy in resource-limited settings. METHODS: Two reviewers independently searched four databases and three conference websites. Full text articles were screened and data extracted using a standardized data extraction form. RESULTS: We retrieved 5812 citations, of which 19 studies reporting second-line failure rates in 2035 patients across low-income and middle-income countries were eligible for inclusion. The cumulative pooled proportion of adult patients failing virologically was 21.8, 23.1, 26.7 and 38.0% at 6, 12, 24 and 36 months, respectively. Most studies did not report adequate information to allow discrimination between drug resistance and poor adherence as reasons for virological failure, but for those that did poor adherence appeared to be the main driver of virological failure. Mortality on second-line was low across all time points. CONCLUSION: Rates of virological failure on second-line therapy are high in resource-limited settings and associated with duration of exposure to previous drug regimens and poor adherence. The main concern appears to be poor adherence, rather than drug resistance, from the limited number of studies accessing both factors. Access to treatment options beyond second-line remains limited and, therefore, a cause for a concern for those patients in whom drug resistance is the identified cause of virological failure. PMID- 22313951 TI - Increased levels of CD4 T-cell activation in individuals with CXCR4 using viruses in primary HIV-1 infection. AB - CXCR4-tropic (X4) HIV-1 variants are associated with faster disease progression compared with CCR5-tropic variants; however, the mechanism for this is unclear. We measured T-cell activation in 120 individuals with primary HIV-1 infection. X4 utilizing variants, determined genotypically, were present in 8.3% of the participants and were associated with higher levels of CD4 T-cell activation, even after adjusting for other prognostic factors. Increased CD4 T-cell activation may influence the more rapid immunological decline associated with X4 virus. PMID- 22313954 TI - Lower than expected maraviroc concentrations in cerebrospinal fluid exceed the wild-type CC chemokine receptor 5-tropic HIV-1 50% inhibitory concentration. AB - To measure maraviroc total cerebrospinal fluid (CSF) concentrations and compare them with total and unbound plasma concentrations. Total maraviroc was measured by reverse-phase high-performance liquid chromatography with tandem mass spectrometry, whereas ultrafiltration was used for unbound maraviroc. Maraviroc was detected in all nine CSF/plasma pairs with a median CSF total concentration of 2.4 ng/ml. CSF concentrations exceeded the 50% inhibitory concentration of wild-type CC chemokine receptor 5-tropic HIV-1 in all specimens. CSF concentrations are lower than expected based on plasma concentrations and physicochemical characteristics. Unbound maraviroc plasma concentrations may be informative in estimating concentrations in CSF. PMID- 22313955 TI - Association of tenofovir exposure with kidney disease risk in HIV infection. AB - OBJECTIVE: Despite widespread HAART use, HIV disease remains associated with increased risk of kidney disease. Whether tenofovir use is associated with higher risk of kidney disease is controversial. DESIGN: We evaluated the association of cumulative and ever exposure to tenofovir on kidney outcomes in 10,841 HIV infected patients from the Veterans Health Administration who initiated antiretroviral therapy from 1997 to 2007. METHODS: Cox proportional hazards and marginal structural models evaluated associations between tenofovir and time to first occurrence of proteinuria (two consecutive urine dipstick measurements >=30 mg/dl), rapid decline in kidney function (>=3 ml/min per 1.73 m annual decline), and chronic kidney disease (CKD; estimated glomerular filtration rate <60 ml/min per 1.73 m). RESULTS: Median follow-up ranged from 3.9 years (proteinuria) to 5.5 years (CKD), during which 3400 proteinuria, 3078 rapid decline, and 533 CKD events occurred. After multivariable adjustment, each year of exposure to tenofovir was associated with 34% increased risk of proteinuria [95% confidence interval (CI) 25-45, P < 0.0001], 11% increased risk of rapid decline (3-18, P = 0.0033), and 33% increased risk of CKD (18-51, P < 0.0001). Preexisting renal risk factors did not appear to worsen the effects of tenofovir. Other antiretroviral drugs showed weaker or inconsistent associations with kidney disease events. Among those who discontinued tenofovir use, risk of kidney disease events did not appear to decrease during follow-up. CONCLUSION: Tenofovir exposure was independently associated with increased risk for three types of kidney disease events, and did not appear to be reversible. Because subtle kidney function decline affects long-term morbidity and mortality, the balance between efficacy and probable adverse effects requires further study. PMID- 22313956 TI - Prevalent tuberculosis and mortality among HAART initiators. AB - The effect of tuberculosis on mortality in people initiating highly-active antiretroviral therapy (HAART) remains unclear; here, we strengthened a previous cohort analysis. Multivariate Cox proportional hazards models were used to assess the association of baseline tuberculosis and time to all-cause mortality among HAART initiators. In reanalysis, treatment for tuberculosis at time of HAART initiation remained unassociated with increased risks of all-cause mortality, with adjusted hazard ratios ranging from 1.00 to 1.09. PMID- 22313957 TI - Glomerular MYH9 expression is reduced by HIV-1. AB - BACKGROUND: The continuing disease burden of HIV-associated nephropathy (HIVAN) warrants better elucidation of its pathogenic mechanisms. Given that loss of MYH9 function causes a Mendelian renal disease, we hypothesized that renal expression of MYH9 is down-regulated by HIV-1 in HIVAN pathogenesis. METHOD AND RESULTS: Using immunofluorescence, we determined that glomerular expression of MYH9 was reduced in the kidneys of HIV-1 transgenic mice. We further determined that Myh9 expression was reduced in HIV-1 transgenic podocytes, statistically significantly at the protein level, and that MYH9 expression was significantly reduced at protein and message level in human podocytes transduced with HIV-1. In analyzing expression in human tissue, we confirmed that MYH9 is abundantly expressed in glomeruli, and podocytes specifically. Finally, we found that MYH9 expression was significantly reduced in human glomeruli in the setting of HIVAN. CONCLUSION: We conclude that the podocyte host response to HIV-1 includes down-regulation of MYH9 expression, and hypothesize that this down-regulation might play a role in the pathogenesis of HIVAN. PMID- 22313958 TI - Small for gestational age birth outcomes in pregnant women with perinatally acquired HIV. AB - OBJECTIVE: To compare small for gestational age (SGA) birth weight in children born to women with perinatally acquired HIV (PAH) vs. those with behaviorally acquired HIV (BAH). DESIGN: Retrospective cohort study of HIV-infected pregnant women who received care and delivered a live born at a single hospital in New York City from January 2004 to April 2011. METHODS: We collected data via chart review on demographics, behavioral risk factors, HIV clinical markers, antiretroviral therapy (ART), mode of HIV acquisition, and pregnancy outcomes on study participants. We compared rates of these exposures among participants by method of HIV acquisition. Generalized Estimating Equation was applied to evaluate the effect of HIV acquisition type on SGA birth weight, adjusting for potential confounders. RESULTS: Of 87 live births evaluated, 17 were born to 14 women with PAH. Overall, 20 (23%) were SGA. Eight of these SGA neonates were born preterm. Live births to women with PAH were more likely to be born SGA in our unadjusted analysis [odds ratio (OR) = 4.13, 95% confidence interval (CI) = 1.38 12.41). After adjusting for mother's age, substance use during pregnancy, nadir CD4 cell count during pregnancy, viral suppression at delivery, and second-line ART use during pregnancy, this relationship persisted with an adjusted OR of 5.7 (95% CI = 1.03-31.61). CONCLUSION: In comparison to infants born to women with BAH, infants born to women with PAH were at high risk for compromised intrauterine growth. Future studies are warranted to determine possible causal mechanisms. PMID- 22313959 TI - Unpacking the recommended indicator for concurrent sexual partnerships. AB - Using sexual behaviour survey data, we examine the methodological choice for the time period underlying the UNAIDS Reference Group on Estimates, Modelling, and Projections recommended 'point prevalence' indicator for concurrency. The results confirm that 6 months before the interview is a good time point for calculating the recommended indicator, but this retrospective estimate is substantially lower than the estimate of concurrency based on the number of current partnerships. The discrepancy is only partially explained by disproportionate missing data in those with more sexual partners. PMID- 22313960 TI - HIV transmission rates from persons living with HIV who are aware and unaware of their infection. AB - Transmission rate modeling estimated secondary infections from those aware and unaware of their HIV infection. An estimated 49% of transmissions were from the 20% of persons living with HIV unaware of their infection. About eight transmissions would be averted per 100 persons newly aware of their infection; with more infections averted the higher the percentage of persons with viral suppression who can be linked to care. Improving all stages of HIV care would substantially reduce transmission rates. PMID- 22313961 TI - HIV infection induces age-related changes to monocytes and innate immune activation in young men that persist despite combination antiretroviral therapy. AB - OBJECTIVES: To compare the impact of HIV infection and healthy ageing on monocyte phenotype and function and determine whether age-related changes induced by HIV are reversed in antiretroviral treated individuals. DESIGN: A cross sectional study of monocyte ageing markers in viremic and virologically suppressed HIV positive males aged 45 years or less and age-matched and elderly (>=65 years) HIV uninfected individuals. METHODS: Age-related changes to monocyte phenotype and function were measured in whole blood assays ex vivo on both CD14(++)CD16(-) (CD14(+)) and CD14(variable)CD16(+) (CD16(+)) subsets. Plasma markers relevant to innate immune activation were measured by ELISA. RESULTS: Monocytes from young viremic HIV-positive males resemble those from elderly controls, and show increased expression of CD11b (P < 0.0001 on CD14(+) and CD16(+)subsets) and decreased expression of CD62L and CD115 (P = 0.04 and 0.001, respectively, on CD14(+) monocytes) when compared with young uninfected controls. These changes were also present in young virologically suppressed HIV-positive males. Innate immune activation markers neopterin, soluble CD163 and CXCL10 were elevated in both young viremic (P < 0.0001 for all) and virologically suppressed (P = 0.0005, 0.003 and 0.002, respectively) HIV-positive males with levels in suppressed individuals resembling those observed in elderly controls. Like the elderly, CD14(+) monocytes from young HIV-positive males exhibited impaired phagocytic function (P = 0.007) and telomere-shortening (P = 0.03) as compared with young uninfected controls. CONCLUSION: HIV infection induces changes to monocyte phenotype and function in young HIV-positive males that mimic those observed in elderly uninfected individuals, suggesting HIV may accelerate age-related changes to monocytes. Importantly, these defects persist in virologically suppressed HIV positive individuals. PMID- 22313962 TI - A role for cytomegalovirus-specific CD4+CX3CR1+ T cells and cytomegalovirus induced T-cell immunopathology in HIV-associated atherosclerosis. AB - OBJECTIVE: HIV-infected individuals are at increased risk for myocardial infarction. Given observations that cytomegalovirus (CMV) infection, CMV-specific T cells, and CX3CR1 have each been associated with atherosclerosis, we hypothesized that CMV-induced T-cell immunopathology could contribute to HIV associated atherosclerosis. METHODS: We measured the expression of CX3CR1 on peripheral blood mononuclear cells and its association with carotid artery intima media thickness (IMT) in 29 HIV-infected individuals and 48 uninfected controls. We analyzed the phenotype and specificity of CX3CR1(+)CD4(+) T cells, the production of CX3CL1 (the ligand of CX3CR1) by CMV-infected endothelial cells in vitro, and the migration of CD4(+) T cells induced by CX3CL1. RESULTS: The progression of atherosclerosis in HIV-infected individuals, as assessed by longitudinal measurements of carotid IMT, was associated with a high frequency of CD4(+) T cells that express the chemokine receptor CX3CR1. Such CD4(+)CX3CR1(+) T cells were antigen-primed, produced high levels of pro-inflammatory cytokines, and composed the majority of the CMV-specific CD4(+) T cells. CMV-stimulated CD4(+) T cells were also found to induce the production of CX3CL1 (the ligand for CX3CR1) by human arterial endothelial cells, driving the transendothelial migration of pro-inflammatory CD4(+) T cells. Finally, we observed that CD4(+)CX3CR1(+) T cells could be localized to the coronary arterial wall in HIV disease. CONCLUSION: HIV-associated atherosclerosis may be driven by a positive feedback pathway in which a high frequency of antigen-stimulated, CMV-specific CD4(+)CX3CR1(+) T cells induce endothelial cells to secrete CX3CL1, which itself drives progressive infiltration of the arterial wall by pro-inflammatory cells. PMID- 22313963 TI - Ritonavir or saquinavir impairs the invasion of cervical intraepithelial neoplasia cells via a reduction of MMP expression and activity. AB - OBJECTIVE AND DESIGN: Treatment of human immunodeficiency virus (HIV)-infected women with the highly active antiretroviral therapy (HAART) has reduced the onset of uterine cervical intraepithelial neoplasia (CIN), and halted its progression to cervical carcinoma. We and others demonstrated that the HIV protease inhibitors (HIV-PIs) used in HAART can exert direct antitumour activities also in HIV-free preclinical or clinical models. As uterine cervical carcinoma is a leading cause of death in women independently of HIV infection, herein we assessed the impact of therapeutic concentrations of HIV-PIs including indinavir (IDV), saquinavir (SQV) or ritonavir (RTV) on cells obtained from CIN or cervical carcinoma lesions of HIV-negative women. METHODS: HIV-PI effects were evaluated by cell invasion, growth or toxicity assays, and by RNA, protein or zymogram analyses. RESULTS: Both SQV and RTV inhibited CIN cell invasion, and this was paralleled by a reduced expression and proteolytic activity of the matrix metalloproteinase (MMP)-2 and 9 in treated cells. SQV and RTV also reduced CIN cell growth rate, but did not affect the invasion or growth of cells derived from highly progressed cervical carcinoma. CONCLUSION: As MMP-2 and MMP-9 have a key role in CIN evolution into cervical carcinoma, these results support the use of SQV or RTV for the block of CIN clinical progression in either HIV-infected or uninfected patients. PMID- 22313964 TI - Pre-disease pregnancy complications and systemic sclerosis: pathogenic or pre clinical? PMID- 22313965 TI - Abnormal erythroid cell proliferation and myelofibrosis in a cat. AB - A cat was presented with severe progressive anemia despite marked erythroblastosis. The cat was negative for feline leukemia virus antigen and feline immunodeficiency virus antibody. Bone marrow cytology revealed an excess of erythroid cells with a predominance of prorubricytes and basophilic rubricytes. No response to immunosuppressive therapy was obtained, and a tentative diagnosis of myelodysplastic syndrome was made. The cat showed a partial response to low-dose cytarabine (20 mg/m(2) subcutaneously q24) but died 51 days after the 1st admission. Histopathological examination revealed fibrosis in the bone marrow and marked infiltration of erythroid cells into other organs. PMID- 22313966 TI - Effect of matrigel on the osteogenic potential of canine adipose tissue-derived mesenchymal stem cells. AB - Adipose tissue-derived mesenchymal stem cells (Ad-MSCs) are a promising source of cells for bone tissue engineering. Matrigel is a basement membrane extract containing multiple extracellular components. This mixture may promote the osteogenic differentiation of MSCs and provide a more appropriate microenvironment for transplanted cells. Here, we investigated the effect of Matrigel on the osteogenic potential of Ad-MSCs. Canine Ad-MSCs were cultured in 2D and 3D matrices and implanted into subcutaneous pouches of dogs either with or without Matrigel. Culture mineralization, cell adhesion efficiency, cell proliferation, osteoid matrix production and alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase activities were quantified and compared. Ad MSCs grown in 2D cultures with Matrigel showed higher levels of calcium deposition and ALP activity than those grown in the absence of Matrigel under osteogenic conditions. In 3D cultures, the cells cultivated with Matrigel showed greater attachment, proliferation and osteogenic differentiation than those grown without Matrigel. In vivo, Ad-MSCs implanted with Matrigel showed higher osteogenic potential than those without Matrigel. In conclusion, these data suggest that the use of Matrigel can increase the osteogenic potential of canine Ad-MSCs. PMID- 22313967 TI - CT and MRI imaging diagnosis of epidural idiopathic sterile pyogranulomatous inflammation in a dog spinal canal. AB - A 12-year-old neutered male shih tzu developed progressive pelvic limb paraparesis. Computed tomography showed a radiolucent mass lesion in the spinal canal at the left side of the 11th thoracic vertebra. The mass was not enhanced by intravenous contrast medium injection. It was hyperintense on both T1- and T2 weighted magnetic resonance images. The signal intensity of the mass was decreased with a fat suppression technique, indicating a fatty origin. After removal of the mass via T11-T12 hemilaminectomy, chronic panniculitis was confirmed by histopathological examination. This case demonstrates the utility of computed tomography and magnetic resonance imaging for the diagnosis of spinal canal pyogranulomatous inflammation. PMID- 22313968 TI - Hexachlorophene and cuprizone induce the spongy change of the developing rat brain by different mechanisms: the role of 2', 3'-cyclic nucleotide 3' phosphodiesterase (CNPase). AB - The goal of this research was to identify mechanisms responsible for the spongy change induced in rats after repeated hexachlorophene (HCP) or cuprizone (CPZ) dosing. Rats were dosed with 35 mg/kg HCP for 5 days followed by drug withdrawal for 7 days suffered spongy changes to the white matter of the cerebrum, cerebellum, medulla oblongata, and spinal cord that were accompanied by degeneration of oligodendroglia. The severity of both lesions increased prominently on day 5; however, the spongy change decreased and degeneration of oligodendroglia reversed on day 12 (7 days after dosing ceased). On day 12, cerebral cortex oligodendroglia were stained strongly by anti-CNPase. Other rats were fed for 8 days with powdered chow containing 1% (w/w) CPZ, which was then withdrawn for 16 days. The rats exhibited the spongy change in the white matter of the cerebrum and cerebellum as well as oligodendroglial cell death from day 3. The severity of both lesions increased prominently on day 8. Cerebral cortex oligodendroglia were stained strongly by anti-CNPase on days 3 to 8 and decreased to the control levels by day 24 (16 days after dosing ceased). Electron microscopy revealed that oligodendroglia frequently displayed apoptotic morphology. These findings suggest that CNPase expression was induced in the course of restoration following HCP-induced insults to oligodendroglia and the myelin sheath, and in the course of demyelination by CPZ-induced damage to oligodendroglia. However, the role of CNPase on both courses is unclear. PMID- 22313969 TI - Assessment for predicting parturition in mares based on prepartum temperature changes using a digital rectal thermometer and microchip transponder thermometry device. AB - The purpose of this study was to observe the changes in body temperature before parturition using a wireless temperature monitoring device (WTMD) and to evaluate the usefulness of body temperature measurements using a digital rectal thermometer (DRT) and a microchip transponder thermometry device (MTTD) for predicting parturition in mares. The body temperatures using a WTMD at 0 hr and 1 hr were significantly different from those at the same time on Days 1-5 (P<0.01). The temperature differences between the morning of Day 0 and at -3 hr, 2 hr, -1 hr and 0 hr using the DRT and MTTD showed a significant drop compared with the temperature differences between the morning and evening of Days 1-5 (P<0.05). Furthermore, when the cutoff value of the temperature differences between the morning and other times was set to <=0, the sensitivities of the DRT and MTTD in the evening of Day 0 and at -3 hr were 43% and 100% and 71% and 86%, respectively. The results suggested that monitoring the body temperature differences between morning and within 3 hr before the time of parturition is a valuable method for predicting parturition in mares. Conversely, this method would be more useful in predicting parturition when used in combination with other observations such as the mammary gland size and waxing of the teat ends because it has nearly a 20% probability of false-positive results prior to the day of parturition. PMID- 22313970 TI - Different dimensions of ageist attitudes among men and women: a multigenerational perspective. AB - BACKGROUND: Ageism, a form of prejudice in which one relates negatively to people due to their age, exists throughout life. However, no attempt has been made to compare ageist attitudes across the life cycle, from young adulthood to old age. Consequently, the current study examined age and gender differences in ageism throughout adulthood. METHODS: 955 Israeli participants (age range: 18-98 years) were divided into three age-groups: young (18-39), middle-aged (40-67), and old (68-98), and were administered the Fraboni Scale of Ageism. Age and gender differences were examined both for the three groups and for subgroups within the older adult cohort. RESULTS: Multivariate analysis of variance revealed that middle-aged participants were significantly more ageist than younger and older groups. Across all age groups, men exhibited more avoidance and stereotypical attitudes toward older adults than women. Among the old age group, participants aged 81-98 held more ageist stereotypes and reported more avoidance of older adults than those aged 68-73. Within the older adult cohort, gender was a significant predictor for ageist attitudes among those aged 68-73 and 81-98, but not for people aged 74-80. CONCLUSIONS: Ageism demonstrates a changing pattern across the life span. While gender differences remain stable, ageist attitudes toward growing old as we age ourselves are constantly changing. In order to gain a better understanding of ageism as a general and global phenomenon, we need to consider the role of such attitudes in different stages of life. PMID- 22313971 TI - Viscoelasticity of the articular cartilage surface in early osteoarthritis. AB - OBJECTIVE: Structural and biochemical changes in articular cartilage occur throughout the pathogenesis of osteoarthritis (OA). Early changes include proteoglycan loss and collagen network disorganization at or near the articular surface. These changes accompany reductions in mechanical properties of cartilage, yet the relationships between mechanics and structure in early OA are poorly defined. Thus, the overall goal of this work was to measure changes in the microscale mechanics and structure of the articular surface in an in vivo model of OA to better understand the early pathogenesis of cartilage degeneration in this disease. DESIGN: A canine cranial cruciate ligament transection (CCL(x)) model was used. The contralateral joint served as an internal control (Ctl). The frequency dependence of the dynamic indentation modulus (E(*)) was evaluated, and creep behavior was measured to estimate the instantaneous (E(i,inst)) and equilibrium (E(i,eq)) indentation moduli and longest creep time-constant (tau). These functional parameters were related to microscopic metrics of cartilage structure and biochemistry, measured by polarized light microscopy and digital densitometry of proteoglycan staining by safranin-O. RESULTS: CCL(x) and Ctl cartilage exhibited frequency sensitivity. E(i,inst), E(i,eq), and tau were lower in CCL(x) vs Ctl cartilage. These mechanical changes were accompanied by a reduction in superficial zone thickness and changes in superficial zone collagen organization, as well as a non-significant reduction in superficial zone proteoglycan staining. CONCLUSIONS: Changes in the microscale viscoelastic behavior of the cartilage surface are a functional hallmark of early OA that accompany significant changes to the microstructural organization of the collagenous extracellular matrix. PMID- 22313972 TI - De-stress and enjoy life. PMID- 22313973 TI - New antiplatelet and anticoagulant drugs. PMID- 22313974 TI - Creating an improved environment for restorative dentistry using periodontal surgery and the Broadrick flag occlusal plane analyzer. PMID- 22313975 TI - Injection of sodium hypochlorite beyond the apical foramen--a case report. AB - The aim of this study was to report a clinical case of extravasation of 1% sodium hypochlorite into the periapical tissues during endodontic treatment. During apical debridement, absence of reflux of the irrigating solution was observed, followed by root canal hemorrhage. The patient immediately complained of intense pain, and a profuse edema and hyperemia was observed on the left side of her face compatible with extravasation of hypochlorite to the periapex. The patient was treated with ibuprofen 600 mg three times per day for three days, a single dose of dexamethasone 4 mg, amoxicillin 500 mg three times per day for seven days, and a cold compress for two days. Regression of the condition began on the fourth day, and normal tissue aspect and absence of sequelae were observed on the 14th day. PMID- 22313976 TI - Potential correlation between periodontitis and coronary heart disease--an overview. AB - The role of periodontal disease remains a headline-generating topic. Periodontal disease, caused chiefly by bacteria, is characterized by inflammation, bacteremia, a strong immune response, and loss of connective tissue attachment and bone. It is speculated that a continuous long-term exposure to oral bacteremia and bacterial toxins induces immune responses that could contribute to coronary atherosclerosis and, in conjunction with other risk factors, lead to coronary heart disease and myocardial infarction. Periodontal disease might initiate pathological changes in blood vessel walls and act as a precursor of atherosclerosis in susceptible hosts. Many causal factors can play a role in heart diseases. Periodontal disease caused by pathogen bacteria as a low-grade inflammation could represent one of several possible causal factors of heart disease. PMID- 22313977 TI - Influence of increment thickness on the similarity of composite shade: a pilot study. AB - The aim of this study was to evaluate the similarity in shade between increments of different composite thicknesses. Fifty test specimens 12 mm in diameter were fabricated and separated into five groups (n = 10) according to sample thickness: 0.5 mm, 1.0 mm, 1.5 mm, 2.0 mm, and 2.5 mm. Specimens were polished with water abrasive papers and silicone points. Next, based on the CIE L*a*b* system, test specimens were submitted to color readouts, and the values obtained for the coordinates L*, a*, and b* for each thickness were compared using one-way ANOVA and a Tukey test (P < 0.05). The results demonstrated that there was a reduction in coordinate L* as the test specimen thickness increased, with statistically significant differences (P < 0.05), except for 2.0 mm and 2.5 mm thicknesses (P > 0.05). Samples 1.5 mm thick presented less variation of a*, while a greater variation occurred for samples 2.5 mm thick, with a significant difference in comparison with the other thicknesses (P < 0.05), except for 2.0 mm (P > 0.05). Samples 0.5 mm thick presented a greater variation of b*, while the lowest variation in this coordinate occurred for samples 2.5 mm thick, which was significantly different from the other samples (P < 0.05). It was concluded that different composite thicknesses do not present similarity of color and have an influence on the final result of esthetic restorations. PMID- 22313978 TI - Adult minimal oral sedation in the general practice setting. AB - Patients who are phobic, elderly, physically disabled, or mentally impaired pose unique challenges in the dental operating environment. Reducing stress during the dental appointment allows for improved cooperation, safety, and clinical efficiency. There is an increased need for dentists who are able to confidently and competently render care to these patients. Adult oral conscious sedation at the minimal level is a valuable way to more effectively manage the specific dental needs of this growing population. PMID- 22313979 TI - Shear bond strength of seventh generation bonding agents on dentin of primary teeth--an in vitro study. AB - This controlled, randomized, in vitro study evaluated the shear bond strength of several seventh generation bonding agents on the dentin of primary teeth. Six different adhesives were used: Xeno IV, Clearfil S3 Bond, Adper Prompt-L-Pop, AdheSE One, Bond Force, and Optibond (control). Ninety primary teeth were prepared by wet grinding with a 320-grit silicon carbide paper on a polishing wheel running at 110 RPM. After 24 hours of storage in water, shear bond strengths of each group were determined. The mean shear bond strength of the tested adhesive systems to primary dentin was 12.27 MPa. One-way ANOVA testing showed a statistically significant difference between adhesive products (P < 0.001). Tukey HSD post hoc tests were used to assess which means were significantly different from one another. There was no statistically significant difference between the fifth generation adhesive system (Optibond) and the two seventh generation systems (Xeno IV and Bond Force), with Optibond exhibiting a lower mean shear bond strength compared to Bond Force. Within the limitations of this study, there is a significant difference between seventh generation bonding materials. Bond Force and Optibond appear to exhibit higher shear bond strengths than the other products. PMID- 22313980 TI - Effects of modifying the bonding protocol on the shear bond strength of metallic and ceramic orthodontic brackets. AB - The purpose of this study was to evaluate the in vitro shear bond strength and failure site of metallic and ceramic orthodontic brackets with modified bonding protocols. Sixty bovine mandibular incisors with similar anatomy were selected and divided into six groups (n = 10). In the first protocol, metallic and ceramic brackets were bonded according to the manufacturers' directions (controls); in the second protocol, the step of photocuring with the primer agent was eliminated; and in the third protocol, the primer agent was applied on the tooth and on the bracket base, followed by application of the composite adhesive on the bracket base, with one-step photocure. The same orthodontic adhesive was used for all groups. Shear bond strengths were measured and adhesive remnant index scores (ARI) were determined after bracket failure. The results demonstrated similar shear bond strengths in the protocols but presented significantly greater values for the metallic groups (two-way ANOVA, P < 0.05). ARI scores were compared with chi-square tests, and the ceramic brackets had significantly greater ARI scores compared to the metallic brackets. Based on these results, the manufacturer's bonding protocol can be modified to save clinical time without compromising adhesion of the brackets. PMID- 22313981 TI - Predictive variables for postoperative pain after 520 consecutive dental extraction surgeries. AB - The aim of this study was to evaluate postoperative pain in patients who had a single tooth or multiple erupted teeth extracted. This research evaluated 520 consecutive dental extraction surgeries in which 680 teeth were removed. Data collection was obtained through a questionnaire of patients and of the undergraduate students who performed all procedures. Pain was evaluated through qualitative self-reported scores at seven days postsurgery. An increased pain level was statistically associated with ostectomy, postoperative complications, and tobacco consumption. Pain that persisted for more than two days was statistically associated with the amount of anesthetic solution used, with a notable increase in surgical time and development of postoperative complications. Periods of pain lasting more than two days could be expected for traumatic surgeries lasting more than 30 minutes. Both severe and prolonged pain were signs of development of postoperative complications, such as alveolar osteitis and alveolar infection. PMID- 22313982 TI - Basic principles of dental office logistics: organizing dental supplies and equipment for optimal accessibility. AB - To maximize office production, dentists should continuously perform treatment related tasks throughout the workday. To this end, the office should logically organize and store dental instruments, disposables, materials, handpieces, and small equipment to optimize accessibility of these items at the moment when the dentist needs them. The office needs multiple copies of these items to prevent their inaccessibility during the workday due to breakdown, inventory depletion, or lack of a sterilized copy of the item when needed. Staff should know where all items are located in the office at all times to minimize the time needed to search for them. This article describes how to organize dental items in an office for optimal accessibility to the dentist during procedures. PMID- 22313983 TI - Acute cervicofacial necrotizing fasciitis: three clinical cases and a review of the current literature. AB - Cervicofacial necrotizing fasciitis (NF) is a rare condition that can quickly become life-threatening if appropriate treatment is delayed. This condition is observed as a rapidly progressive infection that causes extensive necrosis of the superficial fascia. This report presents a case of cervicofacial NF with microbiological isolation of methicillin-resistant Staphylococcus aureus in a patient with a history of uncontrolled diabetes mellitus following a minor scalp trauma. The article also presents two cases of NF secondary to odontogenic infection. The radiographic finding of the presence of gas locules in the facial planes on the CT scan helped to confirm the diagnosis. Patients were treated with broad-spectrum antibiotic therapy, extensive surgical drainage, debridement, and supportive care. Awareness in the dental community of the signs of NF will facilitate optimal patient management. PMID- 22313984 TI - Diffuse gingival enlargement. Pharmacologically induced gingival hyperplasia. PMID- 22313985 TI - Focal gingival hyperpigmentation. Intramucosal melanocytic nevus. PMID- 22313986 TI - C-reactive protein as a marker of periodontal disease. AB - Periodontal subgingival pathogens affect local and systemic immune and inflammatory response and cause the release of cytokines; this results in periodontal destruction and initiation of an acute phase systemic inflammatory response characterized by the release of C-reactive proteins (CRP). This study set out to evaluate the serum concentration of CRP that can be used as a marker of periodontal disease as well as a risk indicator for cardiovascular disease. Based on their periodontal status, 45 patients were divided into three groups. The following clinical parameters were recorded: plaque index, gingival index, bleeding index, probing pocket depth, and clinical attachment levels. Scoring was done on six tooth surfaces for all teeth. For the CRP assessment, blood samples were collected from subjects at the time of clinical examination. The results indicated an increase in serum CRP levels in patients with generalized aggressive periodontitis and chronic periodontitis as compared to controls. PMID- 22313987 TI - A new intraoral device to facilitate preparation of the guide plane for removable dental prostheses. AB - This article presents a prototype of an intraoral device that facilitates preparation of parallel guide planes with accuracy and minimal occlusal divergence. The design of this device facilitates transfer of the desired path of insertion from the diagnostic cast to the mouth quickly and efficiently. PMID- 22313988 TI - Influence of restorative techniques on marginal adaptation and dye penetration around Class V restorations. AB - The aim of this study was to observe the influence of restorative techniques on marginal adaptation and dye penetration around Class V restorations simulating abfraction lesions. Sixty mandibular premolars were divided into six groups (n = 10) using different restorative materials. Cavity preparation presented the gingival wall localized in dentin and the incisal wall in enamel. Replicas of abfraction lesions were obtained and viewed under a stereomicroscope for adaptation assessment. All teeth were subjected to thermocycling and mechanical load cycling and immersed in 0.5% methylene blue dye (pH 7.2) for four hours. The results were tabulated and submitted to Kruskal-Wallis tests, which were significant for the dentin margin with lower microleakage values for primer/Vitremer, followed by Clearfil SE Bond/Durafill VS and Clearfil SE Bond/Z100 in qualitative and quantitative methods (P < 0.05). The enamel margin had no significant difference for microleakage values for all groups. There was no statistically significant difference among the substrates for marginal adaptation. The Spearman coefficient illustrated a direct relation between enamel and dentin for microleakage evaluation (P < 0.0001). The data demonstrated no difference for marginal fit by chi-square test. It can be concluded that all groups had microleakage in different degrees, with the lowest values for resin modified glass ionomer. PMID- 22313989 TI - A simple, time-saving chairside device for radiographic diagnosis of vertical bone height and soft tissue thickness for implant placement--clinical report. AB - A diagnostic radiograph of the posterior regions of the jaws is mandatory if implant placement is considered at these sites. The goal is to avoid damage to important anatomical structures such as the inferior alveolar canal and maxillary sinus. Using radiographs to evaluate the remaining bone height available for implant insertion is a common procedure. Many articles have evaluated the success rates of fixed prostheses supported by osseointegrated implants, indicating high rates of success for prostheses 5-10 years in function. However, if an orthopantomogram machine is not readily available, periapical radiographs can be used for vertical bone height assessment. The familiar procedure of incorporating a metal ball of known diameter into an acrylic template is the method of choice. This is a relatively tedious and expensive procedure involving multiple steps, including impression taking, creation of a study model, and manufacture of a metal ball-bearing acrylic template. A further disadvantage for the patient is that a diagnostic radiograph can be taken only at the next appointment. This paper describes a quick and simple method to obtain a radiographic evaluation of remaining alveolar bone height and soft tissue thickness prior to implant placement with help of a metal ball device to avoid template fabrication and time consumption. Soft tissue thickness is measured nonsurgically. PMID- 22313990 TI - Effect of light source and solvent on the sorption and solubility of two dual cured cements photocured through ceramic. AB - The purpose of this study was to verify the polymerization efficiency of two curing units through a ceramic barrier. Forty specimens apiece of two resin luting cements (AllCem and RelyX U100) were made in a stainless steel mold. The experimental group was photocured through a ceramic barrier, while the control group was photocured without a barrier. The specimens were stored in deionized water or 75% ethanol for 28 days and submitted to tests of sorption and solubility (ISO 4049:2000). Values obtained were subjected to ANOVA and Tukey multiple comparison tests (P < 0.05). RelyX U100 suffered more sorption and solubility than AllCem. The light sources did not influence sorption and solubility values, except for the specimens of RelyX U100 that were photocured with an LED unit through ceramic and stored in ethanol; these specimens demonstrated higher values than those photocured using a halogen lamp. PMID- 22313991 TI - Forced orthodontic extrusion and use of CAD/CAM technique for reconstruction of a maxillary central incisor with a severely damaged crown: rehabilitation with a multidisciplinary approach. AB - Dentists encounter fractured anterior teeth on a regular basis. Various methods have been reported in the literature for rehabilitation of an extremely compromised tooth. This report presents a case where esthetic rehabilitation of a fractured maxillary right central incisor was performed employing a multidisciplinary approach: conventional endodontic treatment followed by orthodontic extrusion and final restoration using a CAD /CAM-fabricated one-piece milled zirconia post and core with a full-coverage zirconia crown. PMID- 22313992 TI - Anesthetic efficacy of articaine for inferior alveolar nerve blocks in patients with symptomatic versus asymptomatic irreversible pulpitis. AB - This study sought to determine the anesthetic efficacy of 4% articaine with 1:100,000 epinephrine in patients with symptomatic and asymptomatic irreversible pulpitis in mandibular posterior teeth and if individual patient factors, pulpal disease characteristics, and previous medication are correlated to local anesthetic success. A second objective was to determine the specificity and sensibility of a cold test for prediction of anesthetic success prior to endodontic treatment. Seventy patients diagnosed with irreversible pulpitis in mandibular posterior teeth received 1.6 mL of 4% articaine with 1:100,000 epinephrine for an inferior alveolar nerve block (IANB) using a metal guide. The anesthetic solution was injected with a computer-preprogrammed delivery system for local anesthesia. Endodontic access was begun 15 minutes after solution deposition; later, patients rated their discomfort using the visual analog scale (VAS). The success rate for the IA NB using articaine was 64.2% in patients with symptomatic irreversible pulpitis and 86.9% in patients with asymptomatic irreversible pulpitis. Cold test prior to root canal treatment had a specificity and sensibility of 12.5% and 87.1%, respectively. The anesthetic efficacy of articaine in irreversible pulpitis is moderately acceptable, and anesthetic success increases when the patient has been premedicated with NSAIDs. The cold test appears to be a favorable indicator for predicting anesthetic success. PMID- 22313993 TI - Difficulty in diagnosing oral paracoccidioidomycosis after topical nystatin usage. AB - Paracoccidioidomycosis (PCM) is caused by a dimorphic fungus called Paracoccidioides brasiliensis and is a disseminated, systemic disorder that involves the lungs and other organs but presents characteristic oral lesions as the prominent feature. This article reports an unusual case of a 56-year-old man who had symptomatic granulomatous lesions in the oral cavity. The patient had received a nystatin-based treatment that masked the presence of fungi and made the diagnosis of PCM difficult. Although nystatin is normally used to treat oral fungal infections such as candidiasis, its topical usage is not appropriate for management of PCM. Once the patient received the correct treatment, he demonstrated a full recovery. PMID- 22313994 TI - Bond strength of two resin cements to titanium after different surface conditioning methods. AB - This study evaluated the bond strength of two resin cements (Panavia F and Super Bond) to titanium after various surface conditioning techniques. The cements were applied using polyethylene tubes. After thermocycling, the specimens were tested in a universal testing machine for shear bond strength. Panavia F demonstrated significantly higher bond strength values than Super Bond. Of the conditioning techniques, Al2O3+Silane+Sinfony and Silano Pen+AP demonstrated significantly lower bond strength values than Al2O3+Cesead II Opaque Primer and 110 um SiOx+Silane. The combination of Panavia and 110 um SiOx+Silane, Al2O3+AP, or Al2O3+Cesead II, and the combination of Super Bond and 110 um SiOx+Silane or Al2O3+Cesead II, can be recommended for improving the bond strength of resin cement to titanium. PMID- 22313995 TI - Anti-apoptotic gene transcription signature of salivary gland neoplasms. AB - BACKGROUND: Development of accurate therapeutic approaches to salivary gland neoplasms depends on better understanding of their molecular pathogenesis. Tumour growth is regulated by the balance between proliferation and apoptosis. Few studies have investigated apoptosis in salivary tumours relying almost exclusively on immunohistochemistry or TUNEL assay. Furthermore, there is no information regarding the mRNA expression profile of apoptotic genes in salivary tumors. Our objective was to investigate the quantitative expression of BCL-2 (anti-apoptotic), BAX and Caspase3 (pro-apoptotic genes) mRNAs in salivary gland neoplasms and examine the association of these data with tumour size, proliferative activity and p53 staining (parameters associated with a poor prognosis of salivary tumours patients). METHODS: We investigated the apoptotic profile of salivary neoplasms in twenty fresh samples of benign and seven samples of malignant salivary neoplasms, using quantitative real time PCR. We further assessed p53 and ki-67 immunopositivity and obtained clinical tumour size data. RESULTS: We demonstrated that BCL-2 mRNA is overexpressed in salivary neoplasms, leading to an overall anti-apoptotic profile. We also found an association between the anti-apoptotic index (BCL-2/BAX) with p53 immunoexpression. A higher proliferative activity was found in the malignant tumours. In addition, tumour size was associated with cell proliferation but not with the transcription of apoptotic genes. CONCLUSION: In conclusion, we show an anti-apoptotic gene expression profile in salivary neoplasms in association with p53 staining, but independent of cell proliferation and tumour size. PMID- 22313996 TI - Complications following prostate needle biopsy requiring hospital admission or emergency department visits - experience from 1000 consecutive cases. AB - OBJECTIVE: * To review a contemporary cohort of patients undergoing a transrectal ultrasound-guided prostate needle biopsy (TRUS PNBx) at a single centre to determine the incidence of major complications necessitating hospital admission or emergency department (ED) visits. PATIENTS AND METHODS: * The charts of 1000 consecutive patients undergoing TRUS PNBx were reviewed. * All patients received peri-procedural antibiotic prophylaxis with either ciprofloxacin or co trimoxazole. * Hospital admission and ED visits within 30 days of the procedure were identified for indication, management and outcome. * Patient comorbidities and biopsy characteristics were reviewed for association with complications. RESULTS: * Of the 1000 patients, 25 (2.5%) had post-biopsy complications requiring hospital admission or an ED visit. * Indications included twelve patients (1.2%) with urosepsis, eight (0.8%) with acute urinary retention requiring urethral catheterization, four (0.4%) with gross haematuria requiring bladder irrigation for <24 h, and one (0.1%) with a transient ischaemia attack 1 day after biopsy. * Patients with urosepsis had an average hospitalization of 5 days, and 75% carried quinolone-resistant Escherichia coli organisms. * All patients with urinary retention had catheters removed within 10 days. No patients with haematuria required a blood transfusion. * No demographic or biopsy variables were particularly associated with development of a post-procedure complication. CONCLUSIONS: * In this large contemporary series of TRUS PNBx, we observed a 2.5% rate of major complications requiring hospital admission or an ED visit. * No clinical or biopsy variables were directly associated with development of complications. * These data may be valuable when counselling patients before biopsy. PMID- 22313997 TI - How do honeybees use their magnetic compass? Can they see the North? AB - While seeking food sources and routes back to their hive, bees make use of their advanced nervous and sensory capacities, which underlie a diverse behavioral repertoire. One of several honeybee senses that is both exceptional and intriguing is magnetoreception - the ability to perceive the omnipresent magnetic field (MF) of the Earth. The mechanism by which animals sense MFs has remained fascinating as well as elusive because of the intricacies involved, which makes it one of the grand challenges for neural and sensory biology. However, investigations in recent years have brought substantial progress to our understanding of how such magneto-receptor(s) may work. Some terrestrial animals (birds) are reported to be equipped even with a dual perception system: one based on diminutive magnetic particles - in line with the original model which has also always been hypothesized for bees - and the other one, as the more recent model describes, based on a sensitivity of some photochemical reactions to MF (radical pair or chemical mechanism). The latter model postulates a close link to vision and supposes that the animals can see the position of the geomagnetic North as a visible pattern superimposed on the picture of the environment. In recent years, a growing body of evidence has shown that radical-pair magnetoreception might also be used by insects. It is realistic to expect that such evidence will inspire a re-examination and extension or confirmation of established views on the honeybee magnetic-compass mechanism. However, the problem of bee magnetoreception will not be solved at the moment that a receptor is discovered. On the contrary, the meaning of magnetoreception in insect life and its involvement in the orchestration of other senses is yet to be fully understood. The crucial question to be addressed in the near future is whether the compass abilities of the honeybee could suffer from radio frequency (RF) smog accompanying modern civilization and whether the fitness of this dominant pollinator might be affected by RF fields. The goal of this review is to provide an overview of the path that the behavioral research on honeybee magnetoreception has taken and to discuss it in the context of contemporary data obtained on other insects. PMID- 22313998 TI - Proanthocyanidin diversity in the EU 'HealthyHay' sainfoin (Onobrychis viciifolia) germplasm collection. AB - This study investigated 37 diverse sainfoin (Onobrychis viciifolia Scop.) accessions from the EU 'HealthyHay' germplasm collection for proanthocyanidin (PA) content and composition. Accessions displayed a wide range of differences: PA contents varied from 0.57 to 2.80 g/100 g sainfoin; the mean degree of polymerisation from 12 to 84; the proportion of prodelphinidin tannins from 53% to 95%, and the proportion of trans-flavanol units from 12% to 34%. A positive correlation was found between PA contents (thiolytic versus acid-butanol degradation; P<0.001; R(2)=0.49). A negative correlation existed between PA content (thiolysis) and mDP (P<0.05; R(2)=-0.30), which suggested that accessions with high PA contents had smaller PA polymers. Cluster analysis revealed that European accessions clustered into two main groups: Western Europe and Eastern Europe/Asia. In addition, accessions from USA, Canada and Armenia tended to cluster together. Overall, there was broad agreement between tannin clusters and clusters that were based on morphological and agronomic characteristics. PMID- 22313999 TI - Autocrine motility factor receptor is involved in the process of learning and memory in the central nervous system. AB - The autocrine motility factor receptor (AMFR) is a multifunctional protein involved in cellular adhesion, proliferation, motility and apoptosis. Our study showed that increased AMFR protein expression in the hippocampus of KM mice correlated with enhanced capacity for learning and memory following the shuttle box test and was significantly elevated in the highest score group. Also, AMF and AMFR mRNA expression positively correlates with the mRNA expression of the synapse marker synaptophysin (Syp). Aging studies in the senescence-accelerated mouse strain (SAM) prone/8 (SAMP8), an animal model of Alzheimer's disease (AD), revealed significantly decreased mRNA and protein expression of AMF and AMFR in the hippocampus. This is especially true for AMFR and AMF protein expression compared with age-matched SAM resistant/1 (SAMR1) mouse strain as the control. Additionally, the low mRNA expression of AMFR could be up-regulated by the four nootropic traditional Chinese medicinal prescriptions (TCMPs): Ba-Wei-Di-Huang decoction (BW), Huang-Lian-Jie-Du decoction (HL), Dang-Gui-Shao-Yao-San (DSS) and Tiao-Xin-Fang decoction (TXF). AMFR protein expression could be up-regulated by two TCMPs, Liu-Wei-Di-Huang decoction (LW) and BW. This indicated that AMFR is involved in the process of learning and memory in the central nervous system. These results may provide useful clues for understanding the etiology of AD. PMID- 22314000 TI - Radiation therapy for angiosarcoma: the 35-year University of Florida experience. AB - BACKGROUND AND PURPOSE: We sought to identify prognostic factors and successful therapeutic approaches when treating angiosarcoma with radiotherapy. MATERIALS AND METHODS: From 1974 to 2009, 41 patients with angiosarcoma were treated with radiotherapy. The median patient age was 67 years. Sixteen angiosarcomas were radiation induced. Tumor sites included the head and the neck in 22 patients, breast in 14, and other sites in five. Thirty-one patients were treated with both surgery and radiotherapy (12 preoperatively and 19 postoperatively) and 10 patients were treated with radiotherapy alone. The median radiotherapy dose was 60 Gy (range, 37.5 to 76 Gy). RESULTS: The 5-year local control and overall survival rates were 64% and 54%, respectively. Median follow-up was 3.7 years. Of the 23 patients who relapsed, 15 had a local failure. Predictors of 5-year local control were nonscalp primary location, tumor size of <=5 cm, radiation-induced tumors, and combined-modality local therapy. Predictors of 5-year overall survival were nonscalp location and a tumor size of <=5 cm. The patients with the best outcomes were treated with surgery and radiotherapy 3 times daily for angiosarcoma that developed after breast-conserving therapy. CONCLUSIONS: For angiosarcomas treated with radiotherapy, outcome varies widely and is impacted by tumor site, size, and resectability. In amenable sites, aggressive treatment with resection and hyperfractionated radiotherapy may offer the best prognosis. PMID- 22314002 TI - Factors influencing time to determination of the recommended phase 2 dose in phase 1 clinical trials. AB - OBJECTIVE: Cancer clinical trials are the means to develop safe and effective novel treatment options for patients. The longer it takes for these trials to reach the recommended phase 2 dose (RP2D), the fewer therapy options are available to patients and physicians. The purpose of this study is to examine the factors that delay RP2D determination in phase 1 clinical trials. METHODS: Thirty five consecutive phase 1 clinical trials for advanced solid tumors that started between February 2006 and March 2009 in a single institution were examined for inclusion. Factors potentially contributing to trial delays were analyzed against time to determination of an RP2D (TDR). RESULTS: Thirty-one phase 1 clinical trials met the inclusion criteria and were included in the statistical analysis. Investigational agents under evaluation included single agent cytotoxic (N=4), monoclonal antibody (N=3), single agent cytostatic/targeted (N=16), or combination of an investigational agent and commercially available systemic chemotherapy (N=8). A protocol defined phase 2 dose decreased the TDR (P<0.001). Other factors that significantly increased TDR included a larger minimum estimated patient sample size (P=0.022), a greater number of predefined dose levels (P<0.001), and a higher number of expansion cohorts (P=0.038). CONCLUSIONS: Including a predefined phase 2 dose and reducing the number of dose levels and expansion cohorts may shorten phase 1 trial TDR. PMID- 22314001 TI - Adherence to adjuvant hormonal therapy and its relationship to breast cancer recurrence and survival among low-income women. AB - OBJECTIVES: Although clinical trials have demonstrated the benefit of adjuvant hormonal therapy for hormone receptor-positive breast cancer, it is not known whether poor medication adherence might impact outcomes, particularly in the context of a low-income population traditionally underrepresented in clinical trials. We explored the relationship between adherence to tamoxifen or selective aromatase inhibitors with cancer recurrence and death in a low-income, Medicaid insured population. METHODS: Using a Medicaid claims-tumor registry and National Death Index data, we evaluated adherence to adjuvant hormonal therapy [defined by the medication possession ratio (MPR)], cancer recurrence, and cancer-specific survival for female breast cancer diagnosed from 1998 to 2002, in North Carolina. Multivariate Cox proportional hazards models and logistic regression models were used to examine the role of adherence on cancer recurrence and survival. RESULTS: The sample consisted of 857 cases, mean age 67.7 years, 56.9% white, 60.9% local stage, with a mean follow-up of 4.4 years. Mean first-year MPR was 77%. MPR adherence was not significantly associated with cancer-related death [adjusted hazards ratio=1.18 (95% confidence interval, 0.54-2.59)], or recurrence [adjusted odds ratio=1.49 (95% confidence interval, 0.78-2.84)]. There was also no significant interaction between adherence and use of concurrent CYP2D6 enzyme inhibitors. DISCUSSION: Hormonal therapy adherence was not associated with breast cancer outcomes in this low-income population with relatively poor adherence. Although suboptimal adherence is considered to be an important clinical problem, its effects on breast cancer outcomes may be masked by patient genetic profiles, tumor characteristics, and behavioral factors. PMID- 22314003 TI - Addition of biological therapies to palliative chemotherapy prolongs survival in patients with peritoneal carcinomatosis of colorectal origin. AB - OBJECTIVES: Combination chemotherapy regimens have shown promising results in patients with metastatic colorectal cancer. However, only very few studies have studied the effect of palliative chemotherapy in peritoneal carcinomatosis (PC) and no data are present incorporating biological therapies in the treatment of PC in colorectal cancer. METHODS: By means of merging with the regional Eindhoven Cancer Registry, all consecutive patients diagnosed with synchronous PC of colorectal origin since the year 2000 treated with palliative chemotherapy in our hospital were included. Data on chemotherapeutic agents used were collected retrospectively. The effect of biological therapies on survival was investigated. RESULTS: Fifty consecutive patients were included. Chemotherapeutic treatment consisted mainly of 5-fluorouracil-based chemotherapy with oxaliplatin. In 22 patients biological therapies were added. Overall survival was 12.5 months [95% confidence interval (CI), 9.2-15.5]. In patients receiving chemotherapy in combination with a biological therapy, overall survival was significantly prolonged as compared with those treated without (18.2 months, 95% CI, 9.5-27.0 vs. 10.1 mo, 95% CI, 6.2-14.1, respectively; P=0.001). Prolongation of survival of patients receiving biological therapies in first-line treatment was even more pronounced, being 22.4 months (95% CI, 15.0-29.5). Similar effects were observed on progression-free survival. CONCLUSIONS: Systemic chemotherapy, once regarded as futile in patients suffering from PC, resulted in an overall survival of 12 months in this unselected group of PC-patients. Addition of biological therapies in the first line of treatment prolonged overall survival to 22.4 months. Although the results of this small study should be interpreted with caution, this promising finding warrants further research. PMID- 22314004 TI - FIV establishes a latent infection in feline peripheral blood CD4+ T lymphocytes in vivo during the asymptomatic phase of infection. AB - BACKGROUND: Feline immunodeficiency virus (FIV) is a lentivirus of cats that establishes a lifelong persistent infection with immunologic impairment. RESULTS: In an approximately 2 year-long experimental infection study, cats infected with a biological isolate of FIV clade C demonstrated undetectable plasma viral loads from 10 months post-infection onward. Viral DNA was detected in CD4+CD25+ and CD4+CD25- T cells isolated from infected cats whereas viral RNA was not detected at multiple time points during the early chronic phase of infection. Viral transcription could be reactivated in latently infected CD4+ T cells ex vivo as demonstrated by detectable FIV gag RNA and 2-long terminal repeat (LTR) circle junctions. Viral LTR and gag sequences amplified from peripheral blood mononuclear cells during early and chronic stages of infection demonstrated minimal to no viral sequence variation. CONCLUSIONS: Collectively, these findings are consistent with FIV latency in peripheral blood CD4+ T cells isolated from chronically infected cats. The ability to isolate latently FIV-infected CD4+ T lymphocytes from FIV-infected cats provides a platform for the study of in vivo mechanisms of lentiviral latency. PMID- 22314005 TI - Global health impact: a basis for labeling and licensing campaigns? AB - Most of the world's health problems afflict poor countries and their poorest inhabitants. There are many reasons why so many people die of poverty-related causes. One reason is that the poor cannot access many of the existing drugs and technologies they need. Another, is that little of the research and development (R&D) done on new drugs and technologies benefits the poor. There are several proposals on the table that might incentivize pharmaceutical companies to extend access to essential drugs and technologies to the global poor.(1) Still, the problem remains - the poor are suffering and dying from lack of access to essential medicines. So, it is worth considering a new alternative. This paper suggests rating pharmaceutical and biotechnology companies based on how some of their policies impact poor people's health. It argues that it might be possible to leverage a rating system to encourage companies to extend access to essential drugs and technologies to the poor. PMID- 22314006 TI - The neuropeptide neuromedin U promotes autoantibody-mediated arthritis. AB - INTRODUCTION: Neuromedin U (NMU) is a neuropeptide with pro-inflammatory activity. The primary goal of this study was to determine if NMU promotes autoantibody-induced arthritis. Additional studies addressed the cellular source of NMU and sought to define the NMU receptor responsible for its pro-inflammatory effects. METHODS: Serum containing arthritogenic autoantibodies from K/BxN mice was used to induce arthritis in mice genetically lacking NMU. Parallel experiments examined whether NMU deficiency impacted the early mast-cell dependent vascular leak response induced by these autoantibodies. Bone-marrow chimeric mice were generated to determine whether pro-inflammatory NMU is derived from hematopoietic cells or stromal cells. Mice lacking the known NMU receptors singly and in combination were used to determine susceptibility to serum transferred arthritis and in vitro cellular responses to NMU. RESULTS: NMU deficient mice developed less severe arthritis than control mice. Vascular leak was not affected by NMU deficiency. NMU expression by bone-marrow-derived cells mediated the pro-arthritogenic effect. Deficiency of all of the known NMU receptors, however, had no impact on arthritis severity and did not affect the ability of NMU to stimulate intracellular calcium flux. CONCLUSIONS: NMU deficient mice are protected from developing autoantibody-induced inflammatory arthritis. NMU derived from hematopoietic cells, not neurons, promotes the development of autoantibody-induced inflammatory arthritis. This effect is mediated by a receptor other than the currently known NMU receptors. PMID- 22314007 TI - Patients aged more than 70 had higher risk of locally advanced prostate cancers and biochemical recurrence in Korea. AB - Study Type - Prognosis (cohort series) Level of Evidence 2b. What's known on the subject? and What does the study add? This study reports that patients aged 70 years or older have a higher possibility of locally advanced cancer than younger patients. Instead of conservative management, radical eradication of clinically localized prostate cancer should be actively considered in well-selected healthy patients older than 70 years. OBJECTIVE: * To analyse the differences in the clinicopathological results between two groups of Korean patients aged younger or older than 70 years with clinically localized prostate cancer. METHODS: * A cohort of consecutive male patients who underwent radical prostatectomy was retrospectively analysed. In total, 995 patients (74.6%) were younger than 70 years, and 338 patients (25.4%) were 70 years or older. * Biochemical recurrence (BCR) -free survival was evaluated in the patients, who were followed up for more than 24 months. * The Kaplan-Meier method was used to calculate survival estimates for BCR-free survival. Multivariate Cox proportional hazard regression analysis was performed to predict non-organ-confined status and BCR. RESULTS: * Mean preoperative prostate-specific antigen (PSA) levels and biopsy or pathological Gleason scores showed no differences between the two age groups. * Older patients, aged more than 70 years, displayed significantly higher risk of locally advanced prostate cancer and BCR than younger patients. * Subgroup analysis showed that the risk of the presence of locally advanced disease was significantly increased in patients of 70 years or older when we compared the proportion of locally advanced disease only in patients with PSA <4 ng/mL. * Multivariate analysis showed that old age, high PSA and high Gleason score were significantly associated with non-organ confined status and BCR. CONCLUSIONS: * Patients aged 70 years or older had a higher possibility of locally advanced cancer than younger patients. * Radical eradication of clinically localized prostate cancer should be actively considered in well-selected healthy patients older than 70 years. PMID- 22314008 TI - Modified cuffed anastomosis technique to treat pseudoaneurysms following thoracic endovascular aortic repair. AB - Pseudoaneurysm after thoracic endovascular aortic repair (TEVAR) is very rare. We report a case of thoracic aortic pseudoaneurysms due to flares at the proximal end of a stent graft after TEVAR for ductal aneurysm. We describe a total aortic arch replacement in this case using a modified cuffed anastomosis technique with an elephant trunk procedure leaving the partial stent graft in situ. PMID- 22314009 TI - Cardiac varix in the right atrium. AB - A 73-year old man underwent transthoracic and transoesophageal echocardiography and computed tomography, which revealed what appeared to be an asymptomatic primary mobile tumour located in the right atrium. During surgery, the mass was found to be associated with the right atrial septum and was subsequently resected. Histopathology of the mass revealed a cardiac varix with phleboliths. The patient had an uneventful postoperative course and no signs of recurrence at the 10-month follow-up. PMID- 22314010 TI - Prediction of postoperative atrial fibrillation in a large coronary artery bypass grafting cohort. AB - The objective of this study was to identify and evaluate predictors of postoperative atrial fibrillation (POAF) in a large coronary artery bypass grafting (CABG) cohort. This was a single centre study of 7115 consecutive patients with preoperative sinus rhythm who underwent isolated CABG between January 1996 and December 2009. Independent risk factors for POAF were identified with multiple logistic regression. The predictive quality of the final model was evaluated by comparing predicted and observed events of POAF, in an effort to find patients at high risk of developing POAF. After CABG, 2270 patients (32%) developed POAF during hospital stay. Independent risk factors of POAF included advancing age (odds ratio, OR 2.0-7.3), preoperative S-creatinine >= 150 umol/l (OR 1.6), male gender (OR 1.2), New York Heart Association class III/IV (OR, 1.2), smoking (OR 1.1), prior myocardial infarction (OR 1.1) and absence of hyperlipidemia (OR 0.9). The final prediction model was moderate (area under curve, 0.62; 95% confidence interval, 0.61-0.64). Patients with POAF had more postoperative complications, including a higher incidence of stroke and increased length of hospital stay. In conclusion, several risk factors for POAF were identified, but the moderate value of the prediction model confirms the difficulty of identifying patients at high risk of developing POAF after CABG. PMID- 22314011 TI - Ventricular assist device therapy in post-cardiotomy cardiogenic shock: historical outcomes and current trends. AB - Ventricular assist device (VAD) therapy has been used successfully as a bridge to recovery, bridge to transplant and in the last decade as a destination therapy. The use of VAD for post-cardiotomy cardiogenic shock (PCCS) is not currently reported in national databases in the UK and Ireland. Data were collected through a telephone survey of chief perfusionists from all the cardiac surgery units in the UK and Ireland between October 2007 and October 2008. Approximately 28 000 adult cardiac surgical procedures were performed at 45 cardiac centres, of which 33 (73%) reported using VAD. The total number of patients supported was 66, of which 41% (n = 27) survived to be discharged home. About 42.5% (n = 28) died during VAD in place, and 16.5% died after successful weaning from VAD. Preferences for device types were Biomedicus (n = 25), Levitronix (n = 10), Sorin (n = 3), roller pump (n = 3) and Berlin heart (n = 2). Despite the reasonable survival rates after VAD use in post-cardiotomy heart failure, there are significant differences in their availability and individual's attitude towards their use. VAD use in PCCS should be prospectively documented in the audit returns of all the units, for further analysis and for generation of protocols. PMID- 22314012 TI - Parental distress, parenting practices, and child adaptive outcomes following traumatic brain injury. AB - Moderate and severe pediatric traumatic brain injuries (TBI) are associated with significant familial distress and child adaptive sequelae. Our aim was to examine the relationship between parental psychological distress, parenting practices (authoritarian, permissive, authoritative), and child adaptive functioning 12-36 months following TBI or orthopedic injury (OI). Injury type was hypothesized to moderate the relationship between parental distress and child adaptive functioning, demonstrating a significantly stronger relationship in the TBI relative to OI group. Authoritarian parenting practices were hypothesized to mediate relationship between parental distress and child adaptive functioning across groups. Groups (TBI n = 21, OI n = 23) did not differ significantly on age at injury, time since injury, sex, race, or SES. Parents completed the Brief Symptom Inventory, Parenting Practices Questionnaire, and Vineland-II. Moderation and mediation hypotheses were tested using hierarchical multiple regression and a bootstrapping approach, respectively. Results supported moderation and revealed that higher parental psychological distress was associated with lower child adaptive functioning in the TBI group only. Mediation results indicated that higher parental distress was associated with authoritarian parenting practices and lower adaptive functioning across groups. Results suggest that parenting practices are an important area of focus for studies attempting to elucidate the relationship between parent and child functioning following TBI. PMID- 22314013 TI - Trophic relationships between predators, whiteflies and their parasitoids in tomato greenhouses: a molecular approach. AB - The whiteflies Bemisia tabaci Gennadius and Trialeurodes vaporariorum (Westwood) (Hemiptera: Aleyrodidae) are two of the main pests in tomato crops. Their biological control in Mediterranean IPM systems is based on the predators Macrolophus pygmaeus (Rambur) and Nesidiocoris tenuis Reuter (Hemiptera: Miridae), as well as on the parasitoids Eretmocerus mundus (Mercet) and Encarsia pergandiella Howard (Hymenoptera: Aphelinidae). These natural enemies may interact with each other and their joint use could interfere with the biological control of those whitefly pests. Analysis of predator-prey interactions under field conditions is therefore essential in order to optimize whitefly control. Species-specific polymerase chain reaction (PCR)-primers were designed to detect DNA fragments of these whiteflies and parasitoids within both predator species in tomato greenhouses. We demonstrated that both predators feed on both whitefly species, as well as on both parasitoids under greenhouse conditions. Prey molecular detection was possible where prey abundance was very low or even where predation was not observed under a microscope. Whitefly DNA detection was positively correlated with adult whitefly abundance in the crop. However, a significant relationship was not observed between parasitoid DNA detection and the abundance of parasitoid pupae, even though the predation rate on parasitoids was high. This unidirectional intraguild predation (predators on parasitoids) could potentially reduce their combined impact on their joint prey/host. Prey molecular detection provided improved detection of prey consumption in greenhouse crops, as well as the possibility to identify which prey species were consumed by each predator species present in the greenhouse, offering a blueprint with wider applicability to other food webs. PMID- 22314014 TI - Analysis of glycoprotein processing in the endoplasmic reticulum using synthetic oligosaccharides. AB - Protein quality control (QC) in the endoplasmic reticulum (ER) comprises many steps, including folding and transport of nascent proteins as well as degradation of misfolded proteins. Recent studies have revealed that high-mannose-type glycans play a pivotal role in the QC process. To gain knowledge about the molecular basis of this process with well-defined homogeneous compounds, we achieved a convergent synthesis of high-mannose-type glycans and their functionalized derivatives. We focused on analyses of UDP-Glc: glycoprotein glucosyltransferase (UGGT) and ER Glucosidase II, which play crucial roles in glycoprotein QC; however, their specificities remain unclear. In addition, we established an in vitro assay system mimicking the in vivo condition which is highly crowded because of the presence of various biomacromolecules. PMID- 22314015 TI - Improving adherence to surveillance and screening recommendations for people with colorectal cancer and their first degree relatives: a randomized controlled trial. AB - BACKGROUND: Colorectal cancer (CRC) is among the leading causes of cancer-related morbidity and mortality worldwide. Despite clinical practice guidelines to guide surveillance care for those who have completed treatment for this disease as well as screening for first degree relatives of people with CRC, the level of uptake of these recommendations remains uncertain. If outcomes for both patients and their families are to be improved, it is important to establish systematic and cost-effective interventions to improve adherence to guideline recommendations for CRC surveillance and screening. METHODS/DESIGN: A randomized controlled trial will be used to test the effectiveness of a print-based intervention to improve adherence to colonoscopy surveillance among people with CRC and adherence to CRC screening recommendations among their first degree relatives (FDRs). People diagnosed with CRC in the past 10 months will be recruited through a population based cancer registry. Consenting participants will be asked if their first degree relatives might also be willing to participate in the trial. Information on family history of CRC will be obtained from patients at baseline. Patients and their families will be randomized to either minimal ethical care or the print based intervention. The print-based intervention for FDRs will be tailored to the participant's level of risk of CRC as determined by the self-reported family history assessment. Follow up data on surveillance and screening participation will be collected from patients and their FDRs respectively at 12, 24 and 36 months' post recruitment. The primary analyses will relate to comparing levels of guideline adherence in usual care group versus print-based group in the patient sample and the FDR sample respectively. DISCUSSION: Results of this study will provide contribute to the evidence base about effective strategies to a) improve adherence to surveillance recommendation for people with CRC; and b) improve adherence to screening recommendation for FDRs of people with CRC. The use of a population-based cancer registry to access the target population may have significant advantages in increasing the reach of the intervention. TRIAL REGISTRATION: This trial is registered with the Australian and New Zealand Clinical Trials Registry Registration Number (ACTRN): ACTRN12609000628246. PMID- 22314016 TI - Interpreting the outcomes of automated internet-based randomized trials: example of an International Smoking Cessation Study. AB - BACKGROUND: Smoking is one of the largest contributors to the global burden of disease. Internet interventions have been shown to reduce smoking rates successfully. However, improved methods of evaluating effectiveness need to be developed for large-scale Internet intervention trials. OBJECTIVE: To illustrate a method to interpret outcomes of large-scale, fully automated, worldwide Internet intervention trials. METHODS: A fully automated, international, Internet based smoking cessation randomized controlled trial was conducted in Spanish and English, with 16,430 smokers from 165 countries. The randomized controlled trial replicated a published efficacy trial in which, to reduce follow-up attrition, 1000 smokers were followed up by phone if they did not provide online follow-up data. RESULTS: The 7-day self-reported abstinence rates ranged from 36.18% (2239/6189) at 1 month to 41.34% (1361/3292) at 12 months based on observed data. Given high rates of attrition in this fully automated trial, when participants unreachable at follow-up were presumed to be smoking, the abstinence rates ranged from 13.63% (2239/16.430) at 1 month to 8.28% (1361/16,430) at 12 months. We address the problem of interpreting results with high follow-up attrition rates and propose a solution based on a smaller study with intensive phone follow-up. CONCLUSIONS: Internet-based smoking cessation interventions can help large numbers of smokers quit. Large-scale international outcome studies can be successfully implemented using automated Internet sites. Interpretation of the studies' results can be aided by extrapolating from results obtained from subsamples that are followed up by phone or similar cohort maintenance methods. TRIAL REGISTRATION: ClinicalTrials.gov NCT00721786; http://clinicaltrials.gov/ct2/show/NCT00721786 (Archived by WebCite at http://www.webcitation.org/63mhoXYPw). PMID- 22314017 TI - Mutational analysis of the West Nile virus NS4B protein. AB - West Nile virus NS4B is a small hydrophobic nonstructural protein approximately 27 kDa in size whose function is poorly understood. Amino acid substitutions were introduced into the NS4B protein primarily targeting two distinct regions; the N terminal domain (residues 35 through 60) and the central hydrophobic domain (residues 95 through 120). Only the NS4B P38G substitution was associated with both temperature-sensitive and small-plaque phenotypes. Importantly, this mutation was found to attenuate neuroinvasiveness greater than 10,000,000-fold and lower viremia titers compared to the wild-type NY99 virus in a mouse model. Full genome sequencing of the NS4B P38G mutant virus revealed two unexpected mutations at NS4B T116I and NS3 N480H (P38G/T116I/N480H), however, neither mutation alone was temperature sensitive or attenuated in mice. Following incubation of P38G/T116I/N480H at 41 degrees C, five mutants encoding compensatory substitutions in the NS4B protein exhibited a reduction in the temperature-sensitive phenotype and reversion to a virulent phenotype in the mouse model. PMID- 22314018 TI - Subtle alteration of residues including N-linked glycans in V2 loop modulate HIV 1 neutralization by PG9 and PG16 monoclonal antibodies. AB - Recent discovery of several potent and broadly neutralizing monoclonal antibodies (MAbs) (such as PG9 and PG16) to HIV-1 provided clues on newer vaccine targets. In the present study, we found an env clone obtained from a slow progressor showing significant resistance to PG9 and PG16 MAbs in sharp contrast to other contemporaneous autologous env clones. By constructing chimeric envelopes and specific substitutions we found that both loop length and spatial orientation of glycan residues in addition to the net charge of the beta sheet C region that directly binds to PG9 CDRH3 within V2 loop significantly modulated HIV-1 sensitivity to PG9 and PG16 MAbs. Similar observation were made with several other Envs which varied in length, glycan content and net charge in PG9 contacting complementary region in V2 loop. Our data indicated that subtle change within V2 loop alone modulates exposition of quaternary epitopes that are targets of PG9/PG16 MAbs. PMID- 22314019 TI - Physiological plasticity, long term resistance or acclimation to temperature, in the Antarctic bivalve, Laternula elliptica. AB - To further investigate the previously reported limited acclimation capacities of Antarctic marine stenotherms, the Antarctic mud clam, Laternula elliptica (King and Broderip, 1830-1831), was incubated at 3.0 degrees C for 89days. The thermal windows of a suite of biochemical and physiological metrics that characterise tissue aerobic status, were then measured in response to acute temperature elevation (2-2.5 degrees C increase per week). To test if acclimation had occurred at the higher temperature, results were compared with published data, from the preceding year, for L. elliptica which had been incubated at ambient temperature (0.0 degrees C) and then subjected to the same acute temperature treatments. Incubation to 3.0 degrees C led to a temperature induced increase of tissue aerobic status (reduced intracellular cCO(2) with increased O(2) consumption, PLA (phospho-L-arginine) and ATP). At the highest acute temperature (7.5 degrees C) the increase in anaerobic pathways (summed acetate/succinate and propionate) was less after 3.0 degrees C than 0.0 degrees C incubation. No other metric shifted its reaction norm in response to acute temperature elevation and so whole animal acclimation had not occurred, even after 3months at 3.0 degrees C. Combined with the constant mortality throughout the 3.0 degrees C incubation period, these data suggest that the recorded physiological changes were either the early stages of acclimation or, more likely, time limited resistance mechanisms. PMID- 22314020 TI - Integrating nitric oxide, nitrite and hydrogen sulfide signaling in the physiological adaptations to hypoxia: A comparative approach. AB - Hydrogen sulfide (H(2)S), nitric oxide (NO) and nitrite (NO(2)(-)) are formed in vivo and are of crucial importance in the tissue response to hypoxia, particularly in the cardiovascular system, where these signaling molecules are involved in a multitude of processes including the regulation of vascular tone, cellular metabolic function and cytoprotection. This report summarizes current advances on the mechanisms by which these signaling pathways act and may have evolved in animals with different tolerance to hypoxia, as presented and discussed during the scientific sessions of the annual meeting of the Society for Experimental Biology in 2011 in Glasgow. It also highlights the need and potential for a comparative approach of study and collaborative effort to identify potential link(s) between the signaling pathways involving NO, nitrite and H(2)S in the whole-body responses to hypoxia. PMID- 22314021 TI - A filter-based propidium monoazide technique to distinguish live from membrane compromised microorganisms using quantitative PCR. AB - Propidium monoazide (PMA) was used to differentiate live from membrane compromised bacteria in PCR methods. We have adapted this technique for use on membrane-filtered water samples and determined its efficacy using qPCR. Independent labs at three institutions replicated these findings. PMID- 22314022 TI - The chronic effects of fish oil with exercise on postprandial lipaemia and chylomicron homeostasis in insulin resistant viscerally obese men. AB - BACKGROUND: Visceral obesity and insulin resistance are associated with a postprandial accumulation of atherogenic chylomicron remnants that is difficult to modulate with lipid-lowering therapies. Dietary fish oil and exercise are cardioprotective interventions that can significantly modify the metabolism of TAG-rich lipoproteins. In this study, we investigated whether chronic exercise and fish oil act in combination to affect chylomicron metabolism in obese men with moderate insulin resistance. METHODS: The single blind study tested the effect of fish oil, exercise and the combined treatments on fasting and postprandial chylomicron metabolism. Twenty nine men with metabolic syndrome were randomly assigned to take fish oil or placebo for four weeks, before undertaking an additional 12 week walking program. At baseline and at the end of each treatment, subjects were tested for concentrations of fasting apo B48, plasma lipids and insulin. Postprandial apo B48 and TAG kinetics were also determined following ingestion of a fat enriched meal. RESULTS: Combining fish oil and exercise resulted in a significant reduction in the fasting apo B48 concentration, concomitant with attenuation of fasting TAG concentrations and the postprandial TAGIAUC response (p < 0.05). Fish oil by itself reduced the postprandial TAG response (p < 0.05) but not postprandial apo B48 kinetics. Individual treatments of fish oil and exercise did not correspond with improvements in fasting plasma TAG and apo B48. CONCLUSION: Fish oil was shown to independently improve plasma TAG homeostasis but did not resolve hyper chylomicronaemia. Instead, combining fish oil with chronic exercise reduced the plasma concentration of pro-atherogenic chylomicron remnants; in addition it reduced the fasting and postprandial TAG response in viscerally obese insulin resistant subjects. PMID- 22314025 TI - Baseline serum MMP-3 levels in patients with Rheumatoid Arthritis are still independently predictive of radiographic progression in a longitudinal observational cohort at 8 years follow up. AB - INTRODUCTION: At present, there is no reliable tool for predicting disease outcome in patients with rheumatoid arthritis (RA). We previously demonstrated an association between specific baseline biomarkers/clinical measures including matrix metalloproteinase-3 (MMP-3) and 2-year radiographic progression in patients with RA. This study further evaluates the predictive capability of these baseline variables with outcome extended over 8-years. METHODS: Fifty-eight of the original cohort (n = 118) had radiographic progression from baseline to mean 8.2-years determined using the van der Heijde modified Sharp method. The contribution of each predictor variable towards radiographic progression was assessed with univariate and multivariate analyses. RESULTS: Traditional factors (including erythrocyte sedimentation rate, C-reactive protein, anti-cyclic citrullinated peptide (anti-CCP), and rheumatoid factor) and biomarkers of tissue destruction (including MMP-3, C-telopeptide of type II collagen, cartilage oligomeric matrix protein, and tissue inhibitor of metalloproteinase 1) measured at baseline were associated with radiographic progression at endpoint. Multivariate logistic regression identified anti-CCP seropositivity [OR 9.29, 95%CI: 2.29-37.64], baseline elevated MMP-3 [OR 8.25, 95%CI: 2.54-26.78] and baseline radiographic damage [OR 5.83, 95%CI: 1.88-18.10] as the strongest independent predictors of radiographic progression. A model incorporating these variables had a predictive accuracy of 0.87, assessed using the area under the receiver operating characteristic curve. CONCLUSION: In our cohort with onset of RA symptoms < 2-years, multivariate analysis identified anti-CCP status and baseline MMP-3 as the strongest independent predictors of radiographic disease outcome at 8.2-years. This finding suggests determination of baseline MMP-3, in conjunction with traditional serologic markers, may provide additional prognostic information for patients with RA. Furthermore, these findings highlight the importance of continued research into a broad range of biomarkers as potential predictors of joint damage. PMID- 22314026 TI - Prospective assessment of histological serial sectioning of pelvic lymph nodes in prostate cancer: a cost-benefit analysis. AB - What's known on the subject? and What does the study add? Metastatic spread to the regional lymph nodes (LNs) is the single worst predictor of survival in prostate cancer. Knowledge of the LN status is crucial, as the treatment strategy is substantially altered in non-organ-confined disease. Current routine pathological protocols for evaluation of LN resection specimens do not demand a minimum of cross-sections per LN to be examined. Depending on the LN size, usually one to two sections are examined. This might lead to underestimation of the true metastatic burden. The present study shows that additional examination of cross-sections in pelvic LNs and applying prostate cancer-specific cytokeratine immunostaining does not lead to significantly increased detection of prostate cancer metastases. However, the work-load and the expenses were significantly higher compared with routine evaluation. OBJECTIVE: To evaluate the diagnostic gain in the detection of lymph node (LN) metastases of prostate cancer and the additional expenses of histological step-section analysis, including immunohistochemistry compared with routine histopathological evaluation. PATIENTS AND METHODS: In a prospective study, 19 patients with prostate cancer at high risk of LN metastases (>cT2c and/or PSA level of >20 ng/mL and/or Gleason score >8) underwent sentinel-guided LN resection. All palpable LNs were submitted to step-section analysis in 200-um sections and concomitant immunohistochemical staining for cytokeratine (AE1/AE3), in addition to routine histopathology of one or two haematoxylin and eosin-stained sections per LN. The number of positive LNs and LN-positive patients for each method was compared; additional expenses in labour time and material for the extended evaluation were estimated. RESULTS: In all, 413 LNs were resected; 220 LNs were palpable and were included in the study. In seven of the 19 patients routine histopathological evaluation revealed LN metastases in 24 of 220 LNs (10.9%). Extended LN evaluation with step sectioning and cytokeratin immunohistochemistry did not reveal any additional patients with LN metastases. In one patient already diagnosed with LN metastases on routine histology, four additional LN metastases were detected upon extended LN evaluation. Three LNs of two patients, one of them pN0, contained disseminated tumour cells. Compared with conventional histological evaluation, serial-section analysis and immunohistochemistry increased expenses in materials and labour time 18.7-fold. CONCLUSIONS: Serial-section analysis seems to have only a minimal diagnostic gain; however, valid conclusions cannot be drawn, as not all LNs were submitted to extended evaluation. Considering the additional expenses, extensive LN evaluation in prostate cancer cannot generally be recommended. PMID- 22314027 TI - The cost associated with disease-related malnutrition in Ireland. AB - OBJECTIVE: The present study aimed to establish the annual public expenditure arising from the health and social care of patients with diet-related malnutrition (DRM) in the Republic of Ireland. DESIGN: Costs were calculated by (i) estimating the prevalence of DRM in health-care settings derived from age standardised comparisons between available Irish data and large-scale UK surveys and (ii) applying relevant costs from official sources to estimates of health care utilisation by adults with DRM. No attempt has been made to estimate separately the costs of DRM and any associated disease, since each can be a cause or consequence of the other. The methods used are adapted from an evaluation of the cost of malnutrition in the UK by the British Association for Parenteral and Enteral Nutrition (2009). Settings Hospitals, nursing homes, out-patient clinics, primary-care clinics and home care. SUBJECTS: All adult patients receiving hospital in-patient, out-patient or specified community health-care services. RESULTS: The annual public health and social care cost associated with adult malnourished patients in Ireland is estimated at over ?1.4 billion, representing 10 % of the health-care budget. Most of this cost arises in acute hospital or residential care settings (i.e. 70 %), with nutritional support estimated to account for <3 % of spend. CONCLUSIONS: The cost associated with the care of patients with DRM is substantial and may rise as the proportion of older people within the population increases, a group at increased risk of DRM. Despite growing pressure on health-care budgets, little attention has been focused on the economic burden associated with DRM in Ireland or the potential for savings arising from improved detection and treatment of those at risk. PMID- 22314028 TI - No evidence for change in oviposition behaviour of Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae) after widespread adoption of transgenic insecticidal cotton. AB - Cotton growing landscapes in Australia have been dominated by dual-toxin transgenic Bt varieties since 2004. The cotton crop has thus effectively become a sink for the main target pest, Helicoverpa armigera. Theory predicts that there should be strong selection on female moths to avoid laying on such plants. We assessed oviposition, collected from two cotton-growing regions, by female moths when given a choice of tobacco, cotton and cabbage. Earlier work in the 1980s and 1990s on populations from the same geographic locations indicated these hosts were on average ranked as high, mid and low preference plants, respectively, and that host rankings had a heritable component. In the present study, we found no change in the relative ranking of hosts by females, with most eggs being laid on tobacco, then cotton and least on cabbage. As in earlier work, some females laid most eggs on cotton and aspects of oviposition behaviour had a heritable component. Certainly, cotton is not avoided as a host, and the implications of these finding for managing resistance to Bt cotton are discussed. PMID- 22314031 TI - Morphology of reproductive accessory glands in eight species of blood-feeding Hemiptera (Hemiptera, Reduviidae) insect vectors of Chagas disease. AB - This paper documents the morphology of previously undescribed adult reproductive accessory glands in eight species of blood-feeding Hemiptera, vectors of Chagas disease. These species are three Triatoma (T. dimidiata, T. klugi, T. sordida), three Rhodnius (R. brethesi, R. nasutus, R. pictipes), and one species each from Nesotriatoma (N. bruneri) and Panstrongylus (P. megistus). This survey shows that the male reproductive systems between species of four genera of Reduviidae adhere to the same general plan seen in previously described vectors of Chagas disease. This morphological similarity suggests that reproductive success of the male is contingent on the delivery of a vital set of male accessory gland secretions to the female in conjunction with material from the testes and seminal vesicle. However, variations were observed in the accessory glands of females, especially at the level of the genus. The spermathecae are morphologically distinct, and the posterior accessory glands are absent in some. The differences in spermathecae morphology likely reflect physiological adaptations associated with speciation driven by cryptic female choice in which the female determines which sperm are used for fertilization. Differences in the posterior reproductive accessory gland can be correlated with variations in ovipositioning behaviour. Since reproductive physiology is important for species success, this information also augments epidemiological studies by providing a comparison to R. prolixus, a Chagas disease vector for which the physiology is well known. PMID- 22314029 TI - Family nurture intervention (FNI): methods and treatment protocol of a randomized controlled trial in the NICU. AB - BACKGROUND: The stress that results from preterm birth, requisite acute care and prolonged physical separation in the Neonatal Intensive Care Unit (NICU) can have adverse physiological/psychological effects on both the infant and the mother. In particular, the experience compromises the establishment and maintenance of optimal mother-infant relationship, the subsequent development of the infant, and the mother's emotional well-being. These findings highlight the importance of investigating early interventions that are designed to overcome or reduce the effects of these environmental insults and challenges. METHODS: This study is a randomized controlled trial (RCT) with blinded assessment comparing Standard Care (SC) with a novel Family Nurture Intervention (FNI). FNI targets preterm infants born 26-34 weeks postmenstrual age (PMA) and their mothers in the NICU. The intervention incorporates elements of mother-infant interventions with known efficacy and organizes them under a new theoretical context referred to collectively as calming activities. This intervention is facilitated by specially trained Nurture Specialists in three ways: 1) In the isolette through calming interactions between mother and infant via odor exchange, firm sustained touch and vocal soothing, and eye contact; 2) Outside the isolette during holding and feeding via the Calming Cycle; and 3) through family sessions designed to engage help and support the mother. In concert with infant neurobehavioral and physiological assessments from birth through 24 months corrected age (CA), maternal assessments are made using standard tools including anxiety, depression, attachment, support systems, temperament as well as physiological stress parameters. Quality of mother-infant interaction is also assessed. Our projected enrolment is 260 families (130 per group). DISCUSSION: The FNI is designed to increase biologically important activities and behaviors that enhance maternally mediated sensory experiences of preterm infants, as well as infant-mediated sensory experiences of the mother. Consequently, we are enlarging the testing of preterm infant neurodevelopment beyond that of previous research to include outcomes related to mother-infant interactions and mother-infant co-regulation. Our primary objective is to determine whether repeated engagement of the mother and her infant in the intervention's calming activities will improve the infant's developmental trajectory with respect to multiple outcomes. Our secondary objective is to assess the effectiveness of FNI in the physiological and psychological co-regulation of the mother and infant. We include aspects of neurodevelopment that have not been comprehensively measured in previous NICU interventions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01439269. PMID- 22314032 TI - Possible alkylation of inorganic Hg(II) by photochemical processes in the environment. AB - The methylation of inorganic Hg by anaerobic bacteria in aquatic environments is considered to be the major pathway for methylmercury (MeHg) production. However, recent research has suggested that abiotic or chemical methylation by humic substances and other low-molecular-weight organic compounds in natural environments is also possible. Here, the aqueous photo-transformation of Hg(2+) to organomercurials was investigated in the presence of ketones, aldehydes and low molecular weight organic acids under UV irradiation. MeHg and/or ethylmercury (EtHg) were identified as the main organomercurial products by multiple analytical techniques, including chromatography-atomic spectrometry and molecular mass spectrometry and further confirmed by stable isotope tracer experiments. The yield of organomercurials was markedly influenced by pH, NaCl concentration, alkylation donor concentration and the presence of chelating ligands in the aqueous solution. Electron paramagnetic resonance spectrometry demonstrated that the radical reaction was not the predominating alkylation pathway, although methyl radicals were detected in the photo-alkylation procedure. A mechanism based on intra-molecular alkyl transfer in the Hg(2+)-low-molecular-weight organic compound complex is proposed. The present work helps us better understand of MeHg and EtHg photo-generation in natural environments. PMID- 22314033 TI - P2X7 receptors in satellite glial cells mediate high functional expression of P2X3 receptors in immature dorsal root ganglion neurons. AB - BACKGROUND: The purinergic P2X3 receptor (P2X3R) expressed in the dorsal root ganglion (DRG) sensory neuron and the P2X7 receptor (P2X7R) expressed in the surrounding satellite glial cell (SGC) are two major receptors participating in neuron-SGC communication in adult DRGs. Activation of P2X7Rs was found to tonically reduce the expression of P2X3Rs in DRGs, thus inhibiting the abnormal pain behaviors in adult rats. P2X receptors are also actively involved in sensory signaling in developing rodents. However, very little is known about the developmental change of P2X7Rs in DRGs and the interaction between P2X7Rs and P2X3Rs in those animals. We therefore examined the expression of P2X3Rs and P2X7Rs in postnatal rats and determined if P2X7R-P2X3R control exists in developing rats. FINDINGS: We immunostained DRGs of immature rats and found that P2X3Rs were expressed only in neurons and P2X7Rs were expressed only in SGCs. Western blot analyses indicated that P2X3R expression decreased while P2X7R expression increased with the age of rats. Electrophysiological studies showed that the number of DRG neurons responding to the stimulation of the P2XR agonist, alpha,beta-meATP, was higher and the amplitudes of alpha,beta-meATP-induced depolarizations were larger in immature DRG neurons. As a result, P2X3R-mediated flinching responses were much more pronounced in immature rats than those found in adult rats. When we reduced P2X7R expression with P2X7R-siRNA in postnatal and adult rats, P2X3R-mediated flinch responses were greatly enhanced in both rat populations. CONCLUSIONS: These results show that the P2X7R expression increases as rats age. In addition, P2X7Rs in SGCs exert inhibitory control on the P2X3R expression and function in sensory neurons of immature rats, just as observed in adult rats. Regulation of P2X7R expression is likely an effective way to control P2X3R activity and manage pain relief in infants. PMID- 22314034 TI - Dynamics of photogenerated surface charge on BiFeO3 films. AB - We report on the spatial and temporal evolution of photoinduced charge generation and carrier separation in heteroepitaxial BiFeO(3) thin films deposited on Nb:SrTiO(3) as measured in ambient at room temperature with Kelvin probe and piezoresponse force microscopy. Contributions from the self-poled and ferroelectric polarization charge are identified from the time evolution of the correlated surface potential and ferroelectric polarization in films as grown and following poling, and at different stages and intensities of optical illumination. Variations in the surface potential with bias voltage, switching history, and illumination intensity indicate how both bulk ferroelectric photovoltaic and the domain wall offset potential mechanisms contribute to the photogenerated charge. PMID- 22314035 TI - [Correlation between physical exercise and visceral fat accumulation among male office workers]. PMID- 22314037 TI - Commentary on Latkauskas et al. PMID- 22314040 TI - Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis. AB - INTRODUCTION: Mesenchymal stem cells (MSCs) can differentiate into various connective tissue cells. Several techniques have been used for the clinical application of MSCs in articular cartilage repair; however, there are many issues associated with the selection of the scaffold material, including its ability to support cell viability and differentiation and its retention and degradation in situ. The application of MSCs via a scaffold also requires a technically demanding surgical procedure. The aim of this study was to test the outcome of intra-articular transplantation of mesenchymal stem cells suspended in hyaluronic acid (HA) in the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis (OA). METHODS: Commercially available human MSCs were cultured, labeled with carboxyfluorescein diacetate succinimidyl ester (CFDA-SE), suspended in either PBS or HA, and injected into the knee joints of 7-month-old animals. The control animals were injected with either PBS or HA alone. The animals were sacrificed at 1, 3, and 5 weeks post transplantation, the knee joints harvested, and fluorescent microscopic analysis was performed. Histological and immunohistochemical analysis were performed at 5 weeks post transplantation. RESULTS: At 5 weeks post transplantation, partial cartilage repair was noted in the HA-MSC group but not in the other groups. Examination of CFDA-SE-labeled cells demonstrated migration, differentiation, and proliferation of MSC in the HA MSC group. There was strong immunostaining for type II collagen around both residual chondrocytes and transplanted MSCs in the OA cartilage. CONCLUSION: This scaffold-free and technically undemanding technique appears to result in the regeneration of articular cartilage in the spontaneous OA animal model. Although further examination of the long-term effects of transplantation is necessary, the findings suggest that intra-articular injection of HA-MSC mixture is potentially beneficial for OA. PMID- 22314041 TI - Lactate infusion during euglycemia but not hypoglycemia reduces subsequent food intake in healthy men. AB - Considering that lactate is known to interact with central glucose-sensing networks, we tested whether hyperlactatemia affects food intake in humans. According to a balanced within-subject 2*2 design, 12 healthy, fasted men (age: 20-40 years; BMI: 20-26 kg/m(2)) were intravenously infused lactate and saline, respectively, for 105 min during concomitant euglycemic and hypoglycemic, respectively, insulin infusion of 75 min. Ten minutes after the simultaneous end of infusions, free-choice food intake was assessed at 10:25 h. Lactate decreased food intake following euglycemia as compared to the other three conditions in which food intake did not differ. Results point to an anorexigenic effect of lactate under euglycemic conditions. PMID- 22314042 TI - A case-control study of chronic prostatitis/chronic pelvic pain syndrome and colorectal cancer. AB - Study Type - Symptom prevalence (case control). Level of Evidence 2b. What's known on the subject? and What does the study add? Associations are well established between intestinal infection/inflammation or inflammatory bowel diseases and colorectal cancer (CRC). Our study found an association between CRC and previously diagnosed chronic prostatitis/chronic pelvic pain syndrome. Patients with CRC had a 1.45-fold higher risk of having a previous diagnosis of chronic prostatitis/chronic pelvic pain syndrome than controls. This phenomenon was found to be more prominent in subjects younger than 60 years. OBJECTIVE: * To estimate the association between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and colorectal cancer (CRC) using a nationwide population-based data set. PATIENTS AND METHODS: * This case-control study used data sourced from the Taiwan Longitudinal Health Insurance Database. * The cases comprised 2899 patients with CRC and 14 995 randomly selected subjects as controls. * We used conditional logistic regression to examine the association between CRC and previous diagnosis of CP/CPPS. RESULTS: * Of the sampled patients, 531(3.05%) had been diagnosed with CP/CPPS before the index date, with 123 (4.24% of the patients with CRC) coming from the cases and 408 individuals (2.81% of patients without CRC) coming from the controls. * Conditional logistic regression analysis revealed that cases were more likely to have CP/CPPS than controls (odds ratio 1.45, 95% CI 1.17-1.79, P < 0.001) after adjusting for the monthly income, geographic location, urbanization level, hypertension, diabetes, renal disease, obesity and cystic kidney disease. * In subgroup analysis, we found the magnitude of the association to be higher in subjects younger than 60 years (age 40-49, odds ratio 2.01; 95% CI 2.04-3.58 and aged 50-59, 2.40, 95% CI 1.48-3.87, both P < 0.001) than among other age groups. CONCLUSION: * We conclude that CP/CPPS patients are at higher risk for CRC, especially in males under 60 years of age. PMID- 22314043 TI - Speech versus song: multiple pitch-sensitive areas revealed by a naturally occurring musical illusion. AB - It is normally obvious to listeners whether a human vocalization is intended to be heard as speech or song. However, the 2 signals are remarkably similar acoustically. A naturally occurring boundary case between speech and song has been discovered where a spoken phrase sounds as if it were sung when isolated and repeated. In the present study, an extensive search of audiobooks uncovered additional similar examples, which were contrasted with samples from the same corpus that do not sound like song, despite containing clear prosodic pitch contours. Using functional magnetic resonance imaging, we show that hearing these 2 closely matched stimuli is not associated with differences in response of early auditory areas. Rather, we find that a network of 8 regions, including the anterior superior temporal gyrus (STG) just anterior to Heschl's gyrus and the right midposterior STG, respond more strongly to speech perceived as song than to mere speech. This network overlaps a number of areas previously associated with pitch extraction and song production, confirming that phrases originally intended to be heard as speech can, under certain circumstances, be heard as song. Our results suggest that song processing compared with speech processing makes increased demands on pitch processing and auditory-motor integration. PMID- 22314044 TI - Interpyramid spike transmission stabilizes the sparseness of recurrent network activity. AB - Cortical synaptic strengths vary substantially from synapse to synapse and exhibit a skewed distribution with a small fraction of synapses generating extremely large depolarizations. Using multiple whole-cell recordings from rat hippocampal CA3 pyramidal cells, we found that the amplitude of unitary excitatory postsynaptic conductances approximates a lognormal distribution and that in the presence of synaptic background noise, the strongest fraction of synapses could trigger action potentials in postsynaptic neurons even with single presynaptic action potentials, a phenomenon termed interpyramid spike transmission (IpST). The IpST probability reached 80%, depending on the network state. To examine how IpST impacts network dynamics, we simulated a recurrent neural network embedded with a few potent synapses. This network, unlike many classical neural networks, exhibited distinctive behaviors resembling cortical network activity in vivo. These behaviors included the following: 1) infrequent ongoing activity, 2) firing rates of individual neurons approximating a lognormal distribution, 3) asynchronous spikes among neurons, 4) net balance between excitation and inhibition, 5) network activity patterns that was robust against external perturbation, 6) responsiveness even to a single spike of a single excitatory neuron, and 7) precise firing sequences. Thus, IpST captures a surprising number of recent experimental findings in vivo. We propose that an unequally biased distribution with a few select strong synapses helps stabilize sparse neuronal activity, thereby reducing the total spiking cost, enhancing the circuit responsiveness, and ensuring reliable information transfer. PMID- 22314045 TI - Human cortical excitability increases with time awake. AB - Prolonged wakefulness is associated not only with obvious changes in the way we feel and perform but also with well-known clinical effects, such as increased susceptibility to seizures, to hallucinations, and relief of depressive symptoms. These clinical effects suggest that prolonged wakefulness may be associated with significant changes in the state of cortical circuits. While recent animal experiments have reported a progressive increase of cortical excitability with time awake, no conclusive evidence could be gathered in humans. In this study, we combine transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to monitor cortical excitability in healthy individuals as a function of time awake. We observed that the excitability of the human frontal cortex, measured as the immediate (0-20 ms) EEG reaction to TMS, progressively increases with time awake, from morning to evening and after one night of total sleep deprivation, and that it decreases after recovery sleep. By continuously monitoring vigilance, we also found that this modulation in cortical responsiveness is tonic and not attributable to transient fluctuations of the level of arousal. The present results provide noninvasive electrophysiological evidence that wakefulness is associated with a steady increase in the excitability of human cortical circuits that is rebalanced during sleep. PMID- 22314047 TI - Repetition suppression versus enhancement--it's quantity that matters. AB - Upon repetition, certain stimuli induce reduced neural responses (i.e., repetition suppression), whereas others evoke stronger signals (i.e., repetition enhancement). It has been hypothesized that stimulus properties (e.g., visibility) determine the direction of the repetition effect. Here, we show that the very same stimuli can induce both repetition suppression and enhancement, whereby the only determining factor is the number of repetitions. Repeating the same, initially novel low-visible pictures of scenes for up to 5 times enhanced the blood oxygen level-dependent (BOLD) response in scene-selective areas, that is, the parahippocampal place area (PPA) and the transverse occipital sulcus (TOS), presumably reflecting the strengthening of the internal representation. Additional repetitions (6-9) resulted in progressively attenuated neural responses indicating a more efficient representation of the now familiar stimulus. Behaviorally, repetition led to increasingly faster responses and higher visibility ratings. Novel scenes induced the largest BOLD response in the PPA and also higher activity in yet another scene-selective region, the retrospenial cortex (RSC). We propose that 2 separable processes modulate activity in the PPA: one process optimizes the internal stimulus representation and involves TOS and the other differentiates between familiar and novel scenes and involves RSC. PMID- 22314046 TI - A meta-analysis of executive components of working memory. AB - Working memory (WM) enables the online maintenance and manipulation of information and is central to intelligent cognitive functioning. Much research has investigated executive processes of WM in order to understand the operations that make WM "work." However, there is yet little consensus regarding how executive processes of WM are organized. Here, we used quantitative meta-analysis to summarize data from 36 experiments that examined executive processes of WM. Experiments were categorized into 4 component functions central to WM: protecting WM from external distraction (distractor resistance), preventing irrelevant memories from intruding into WM (intrusion resistance), shifting attention within WM (shifting), and updating the contents of WM (updating). Data were also sorted by content (verbal, spatial, object). Meta-analytic results suggested that rather than dissociating into distinct functions, 2 separate frontal regions were recruited across diverse executive demands. One region was located dorsally in the caudal superior frontal sulcus and was especially sensitive to spatial content. The other was located laterally in the midlateral prefrontal cortex and showed sensitivity to nonspatial content. We propose that dorsal-"where"/ventral "what" frameworks that have been applied to WM maintenance also apply to executive processes of WM. Hence, WM can largely be simplified to a dual selection model. PMID- 22314048 TI - Pink nodule on the forearm: challenge. PMID- 22314049 TI - Synthetic biology and the development of tools for metabolic engineering. AB - Synthetic biology can significantly advance metabolic engineering by contributing tools (minimal hosts, vectors, genetic controllers, characterized enzymes). The development of these tools significantly reduced the costs and time to develop the antimalarial drug artemisinin, but the availability of more tools could have reduced these costs substantially. PMID- 22314050 TI - The relationship between breastfeeding and weight status in a national sample of Australian children and adolescents. AB - BACKGROUND: Breastfeeding has been shown consistently in observational studies to be protective of overweight and obesity in later life. This study aimed to investigate the association between breastfeeding duration and weight status in a national sample of Australian children and adolescents. METHODS: A secondary analysis of the 2007 Australian National Children's Nutrition and Physical Activity Survey data involving 2066, males and females aged 9 to 16 years from all Australian states and territories. The effect of breastfeeding duration on weight status was estimated using multivariate logistic regression analysis. RESULTS: Compared to those who were never breastfed, children breastfed for >=6 months were significantly less likely to be overweight (adjusted odds ratio: 0.64, 95%CI: 0.45, 0.91) or obese (adjusted odds ratio: 0.51, 95%CI: 0.29, 0.90) in later childhood, after adjustment for maternal characteristics (age, education and ethnicity) and children's age, gender, mean energy intake, level of moderate and vigorous physical activity, screen time and sleep duration. CONCLUSIONS: Breastfeeding for 6 or more months appears to be protective against later overweight and obesity in this population of Australian children. The beneficial short-term health outcomes of breastfeeding for the infant are well recognised and this study provides further observational evidence of a potential long-term health outcome and additional justification for the continued support and promotion of breastfeeding to six months and beyond. PMID- 22314051 TI - Characterization and polymorphism analysis of phosphoglucose isomerase gene in the fall webworm (Hyphantria cunea). AB - Phosphoglucose isomerase (PGI) plays an important role in energy metabolism, and it is documented that PGI exhibits an extensive polymorphism which can affect insects' fitness and adaptation. In this paper, we studied the structural characteristics and polymorphism of pgi gene in the fall webworm (Hyphantria cunea), an important invasive pest in some European and Asian countries. A 2110 bp pgi full-length cDNA encoding a polypeptide of 556 amino acids was obtained from H. cunea. The pgi full-length in the H. cunea genomic DNA was 14,332 bp with 12 exons and 11 introns, similar to the structures of pgi in other Lepidoptera species. We compared the structures of pgi in different insect species. Moreover, thirteen pgi genotypes comprised of five alleles were identified in the Chinese population. Genotypes pgi-cd, pgi-cc and pgi-ce were the most prevalent with over 70% of individuals allocated to them. Four out of five alleles were sequenced the cDNA full-length. Thirty stably variable sites were found among them with five non-synonymous mutation sites. The frequencies of alleles and genotypes were variable in different Chinese geographic subpopulations. Moreover, comparison of pgi mRNA expression levels in each stage of the moth's lifecycle showed that a high expression level was in the 6th instar larval stage, followed by that in the egg and adult stages. The results will provide a basis for further study of the role of different alleles and genotypes of PGI on fitness and adaptation of the moth H. cunea. PMID- 22314052 TI - Synthesis of high quality monolayer graphene at reduced temperature on hydrogen enriched evaporated copper (111) films. AB - We report new findings on the chemical vapor deposition (CVD) of monolayer graphene with negligible defects (>=95% negligible defect-peak over 200 MUm * 200 MUm areas) on evaporated copper films. Compared to copper foils used in the CVD of graphene, several new unexpected results have been observed including high quality monolayer synthesis at temperatures <900 degrees C, a new growth window using a hydrogen-free methane precursor for low-defects, and electron microscope evidence of commensurate growth of graphene grains on underlying copper grains. These thermal, chemical, and physical growth characteristics of graphene on copper films can be attributed to the distinct differences in the dominant crystal orientation of copper films (111) versus foils (100), and consequent dissimilar interplay with the precursor gas. This study suggests that reduced temperature, hydrogen-free synthesis of defect-negligible monolayer graphene is feasible, with the potential to shape and scale graphene grains by controlling the size and crystal orientation of the underlying copper grains. PMID- 22314053 TI - The efficacy of a brief, peer-led nutrition education intervention in increasing fruit and vegetable consumption: a wait-list, community-based randomised controlled trial. AB - OBJECTIVE: The objective of the present research was to test the efficacy of Fruit & Veg $ense sessions in increasing fruit and vegetable consumption. DESIGN: A wait-list randomised controlled trial was conducted (n 292). Intervention participants attended a Fruit & Veg $ense session and received newsletters at weeks 2 and 5 after attending the session. All participants completed an FFQ and a questionnaire measuring knowledge, attitudes, barriers and stage of change for fruit and vegetable consumption at baseline and 6 weeks. SETTING: Hunter region of New South Wales, Australia. SUBJECTS: Two hundred and ninety-two parents with children of primary school age. RESULTS: The intervention group significantly increased its mean consumption of fruit and vegetables by 0.62 servings compared with 0.11 in the control group (difference of 0.51, P = 0.001). Compared with the control group, there were significant increases in intervention participants' knowledge of daily recommended servings (for fruit and vegetables) and serving size (for vegetables), improvement in stage of change for vegetable consumption and a decrease in the number of perceived barriers to fruit and vegetable consumption. CONCLUSIONS: Fruit & Veg $ense is efficacious in increasing fruit and vegetable consumption among parents of primary-school children. The study adds significantly to the limited evidence regarding fruit and vegetable interventions and the feasibility of engaging peer educators to deliver community education sessions. A broader implementation trial to test the effectiveness of Fruit & Veg $ense is recommended. PMID- 22314054 TI - O-GlcNAcase is essential for embryonic development and maintenance of genomic stability. AB - Dysregulation of O-GlcNAc modification catalyzed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) contributes to the etiology of chronic diseases of aging, including cancer, cardiovascular disease, type 2 diabetes, and Alzheimer's disease. Here we found that natural aging in wild-type mice was marked by a decrease in OGA and OGT protein levels and an increase in O-GlcNAcylation in various tissues. Genetic disruption of OGA resulted in constitutively elevated O GlcNAcylation in embryos and led to neonatal lethality with developmental delay. Importantly, we observed that serum-stimulated cell cycle entry induced increased O-GlcNAcylation and decreased its level after release from G2/M arrest, indicating that O-GlcNAc cycling by OGT and OGA is required for precise cell cycle control. Constitutively, elevated O-GlcNAcylation by OGA disruption impaired cell proliferation and resulted in mitotic defects with downregulation of mitotic regulators. OGA loss led to mitotic defects including cytokinesis failure and binucleation, increased lagging chromosomes, and micronuclei formation. These findings suggest an important role for O-GlcNAc cycling by OGA in embryonic development and the regulation of the maintenance of genomic stability linked to the aging process. PMID- 22314055 TI - Support for seasonal influenza vaccination requirements among US healthcare personnel. AB - OBJECTIVE: To measure support for seasonal influenza vaccination requirements among US healthcare personnel (HCP) and its associations with attitudes regarding influenza and influenza vaccination and self-reported coverage by existing vaccination requirements. DESIGN: Between June 1 and June 30, 2010, we surveyed a sample of US HCP ([Formula: see text]) recruited using an existing probability based online research panel of participants representing the US general population as a sampling frame. SETTING: General community. PARTICIPANTS: Eligible HCP who (1) reported having worked as medical doctors, health technologists, healthcare support staff, or other health practitioners or who (2) reported having worked in hospitals, ambulatory care facilities, long-term care facilities, or other health-related settings. METHODS: We analyzed support for seasonal influenza vaccination requirements for HCP using proportion estimation and multivariable probit models. RESULTS: A total of 57.4% (95% confidence interval, 53.3%-61.5%) of US HCP agreed that HCP should be required to be vaccinated for seasonal influenza. Support for mandatory vaccination was statistically significantly higher among HCP who were subject to employer-based influenza vaccination requirements, who considered influenza to be a serious disease, and who agreed that influenza vaccine was safe and effective. CONCLUSIONS: A majority of HCP support influenza vaccination requirements. Moreover, providing HCP with information about the safety of influenza vaccination and communicating that immunization of HCP is a patient safety issue may be important for generating staff support for influenza vaccination requirements. PMID- 22314056 TI - Mandatory influenza vaccine. PMID- 22314057 TI - Caveat emptor: the role of suboptimal bronchoscope repair practices by a third party vendor in a pseudo-outbreak of pseudomonas in bronchoalveolar lavage specimens. AB - OBJECTIVE: To describe a pseudo-outbreak associated with loose bronchoscope biopsy ports caused by inadequate bronchoscope repair practices by third-party vendors and to alert healthcare personnel to assess bronchoscope repair practices. DESIGN: Outbreak investigation. SETTING: A 925-bed tertiary care hospital in Baltimore, Maryland. PATIENTS: Patients who underwent bronchoscopy with certain bronchoscopes after they had been repaired by a third-party vendor. METHODS: An epidemiologic investigation was conducted to determine the cause of Pseudomonas putida growth in 4 bronchoalveolar lavage (BAL) specimens within a 3 day period in May 2008. All bronchoscopes were inspected, and cultures were obtained from bronchoscopes and the environment. Bronchoscope cleaning and maintenance practices were reviewed. Microbiologic results from BAL specimens and medical records were reviewed to find additional cases. RESULTS: All 4 case patients had undergone bronchoscopy with one of 2 bronchoscopes, both of which had loose biopsy ports. Bronchoscope cultures grew P. putida, Pseudomonas aeruginosa, and Stenotrophomonas. The P. putida strains from the bronchoscopes matched those from the patients. Specimens from 12 additional patients who underwent bronchoscopy with these bronchoscopes grew P. putida, P. aeruginosa, or Stenotrophomonas. No patients developed clinical signs or symptoms of infection, but 7 were treated with antibiotics. Investigation revealed that the implicated bronchoscopes had been sent to an external vendor for repair; examination by the manufacturer revealed irregularities in repairs and nonstandard part replacements. CONCLUSIONS: Third-party vendors without access to proprietary information may contribute to mechanical malfunction of medical devices, which can lead to contamination and incomplete disinfection. PMID- 22314058 TI - Lessons learned from outbreaks and pseudo-outbreaks associated with bronchoscopy. PMID- 22314059 TI - Electronic-eye faucets: Legionella species contamination in healthcare settings. AB - OBJECTIVE: To compare heterotrophic plate counts (HPCs) and Legionella species growth from electronic and manual faucet water samples. DESIGN: Proportions of water samples with growth and colony-forming units were compared using Fisher's exact test and the Wilcoxon rank-sum test, respectively. SETTING: Two psychiatric units and 1 medical unit in a 1,000-bed university hospital. METHODS: Water samples were collected from 20 newly installed electronic faucets and 20 existing manual faucets in 3 hospital units. Manual faucets were located in rooms adjacent to the electronic faucets and received water from the same source. Water samples were collected between December 15, 2008, and January 29, 2009. Four electronic faucets were dismantled, and faucet components were cultured. Legionella species and HPC cultures were performed using standard methods. RESULTS: Nearly all electronic faucets (19/20 [95%]) grew Legionella species from at least 1 water sample, compared with less than half (9/20 [45%]) of manual faucets ([Formula: see text]). Fifty-four (50%) of 108 electronic faucet water cultures grew Legionella species, compared with 11 (15%) of 75 manual faucet water cultures ([Formula: see text]). After chlorine dioxide remediation, 4 (14%) of 28 electronic faucet and 1 (3%) of 30 manual faucet water cultures grew Legionella species ([Formula: see text]), and 8 (29%) electronic faucet and 2 (7%) manual faucet cultures had significant HPC growth ([Formula: see text]). All 12 (100%) of the internal faucet components from 2 electronic faucets grew Legionella species. CONCLUSIONS: Electronic faucets were more commonly contaminated with Legionella species and other bacteria and were less likely to be disinfected after chlorine dioxide remediation. Electronic faucet components may provide points of concentrated bacterial growth. PMID- 22314060 TI - Electronic-eye faucets-curse or blessing? PMID- 22314061 TI - Seasonal influenza vaccine compliance among hospital-based and nonhospital-based healthcare workers. AB - BACKGROUND: Influenza vaccination among nonhospital healthcare workers (HCWs) is imperative, but only limited data are available for factors affecting their compliance. OBJECTIVE: To examine the factors influencing influenza vaccine compliance among hospital and nonhospital HCWs. Design and Setting. A vaccine compliance questionnaire was administered to HCWs working in myriad healthcare settings in March-June 2011. METHODS: Online and paper surveys were used to assess compliance with the 2010/2011, 2009/2010, and H1N1 influenza vaccines and to examine factors that predicted the uptake of the 2010/2011 seasonal influenza vaccine. RESULTS: In all, 3,188 HCWs completed the survey; half of these ([Formula: see text]) reported no hospital work time. Compliance rates for all 3 vaccines were significantly higher ([Formula: see text]) among hospital versus nonhospital HCWs. In logistic regression stratified by hospital versus nonhospital setting, and when controlling for demographics and past behavior, the determinants of vaccination against the 2010/2011 seasonal influenza among nonhospital-based HCWs included having a mandatory vaccination policy, perceived importance, no fear of vaccine adverse effects, free and on-site access, and perceived susceptibility to influenza. Determinants of hospital-based HCW vaccine compliance included having a mandatory vaccination policy, belief that HCWs should be vaccinated every year, occupational health encouragement, perceived importance of vaccination, on-site access, and no fear of vaccine adverse effects. The strongest predictor of compliance for both worker groups was existence of a mandatory vaccination policy. CONCLUSIONS: The reasons for vaccine uptake among nonhospital-based versus hospital-based HCWs differed. Targeted interventions should be aimed at workers in these settings to increase their vaccine compliance, including implementing a mandatory vaccination policy. PMID- 22314062 TI - Economic impact of ventilator-associated pneumonia in a large matched cohort. AB - OBJECTIVE: To evaluate the economic impact of ventilator-associated pneumonia (VAP) on length of stay and hospital costs. Design. Retrospective matched cohort study. SETTING: Premier database of hospitals in the United States. PATIENTS: Eligible patients were admitted to intensive care units (ICUs), received mechanical ventilation for >=2 calendar-days, and were discharged between October 1, 2008, and December 31, 2009. METHODS: VAP was defined by International Classification of Diseases, Ninth Revision (ICD-9), code 997.31 and ventilation charges for >=2 calendar-days. We matched patients with VAP to patients without VAP by propensity score on the basis of demographics, administrative data, and severity of illness. Cost was based on provider perspective and procedural cost accounting methods. RESULTS: Of 88,689 eligible patients, 2,238 (2.5%) had VAP; the incidence rate was 1.27 per 1,000 ventilation-days. In the matched cohort, patients with VAP ([Formula: see text]) had longer mean durations of mechanical ventilation (21.8 vs 10.3 days), ICU stay (20.5 vs 11.6 days), and hospitalization (32.6 vs 19.5 days; all [Formula: see text]) than patients without VAP ([Formula: see text]). Mean hospitalization costs were $99,598 for patients with VAP and $59,770 for patients without VAP ([Formula: see text]), resulting in an absolute difference of $39,828. Patients with VAP had a lower in hospital mortality rate than patients without VAP (482/2,144 [22.5%] vs 630/2,144 [29.4%]; [Formula: see text]). CONCLUSIONS: Our findings suggest that VAP continues to occur as defined by the new specific ICD-9 code and is associated with a statistically significant resource utilization burden, which underscores the need for cost-effective interventions to minimize the occurrence of this complication. PMID- 22314063 TI - The efficacy of daily bathing with chlorhexidine for reducing healthcare associated bloodstream infections: a meta-analysis. AB - DESIGN: Systematic review and meta-analysis of randomized controlled trials and quasi-experimental studies to assess the efficacy of daily bathing with chlorhexidine (CHG) for prevention of healthcare-associated bloodstream infections (BSIs). SETTING: Medical, surgical, trauma, and combined medical surgical intensive care units (ICUs) and long-term acute care hospitals. PARTICIPANTS: Inpatients. METHODS: Data on patient population, diagnostic criteria for BSIs, form and concentration of topical CHG, incidence of BSIs, and study design were extracted. RESULTS: One randomized controlled trial and 11 nonrandomized controlled trials reporting a total of 137,392 patient-days met the inclusion criteria; 291 patients in the CHG arm developed a BSI over 67,775 patient-days, compared with 557 patients in the control arm over 69,617 catheter days. CHG bathing resulted in a reduced incidence of BSIs: the pooled odds ratio using a random-effects model was 0.44 (95% confidence interval, 0.33-0.59; [Formula: see text]). Statistical heterogeneity was moderate, with an I(2) of 58%. For the subgroup of studies that examined central line-associated BSIs, the odds ratio was 0.40 (95% confidence interval, 0.27-0.59). CONCLUSIONS: Daily bathing with CHG reduced the incidence of BSIs, including central line-associated BSIs, among patients in the medical ICU. Further studies are recommended to determine the optimal frequency, method of application, and concentration of CHG as well as the comparative effectiveness of this strategy relative to other preventive measures available for reducing BSIs. Future studies should also examine the efficacy of daily CHG bathing in non-ICU populations at risk for BSI. PMID- 22314064 TI - A crossover trial of antimicrobial scrubs to reduce methicillin-resistant Staphylococcus aureus burden on healthcare worker apparel. AB - BACKGROUND: The impact of antimicrobial scrubs on healthcare worker (HCW) bacterial burden is unknown. Objective. To determine the effectiveness of antimicrobial scrubs on hand and apparel bacterial burden. DESIGN: Prospective, crossover trial. SETTING AND PARTICIPANTS: Thirty HCWs randomized to study versus control scrubs in an intensive care unit. METHODS: Weekly microbiology samples were obtained from scrub abdominal area, cargo pocket, and hands. Mean log colony forming unit (CFU) counts were calculated. Compliance with hand hygiene practices was measured. Apparel and hand mean log CFU counts were compared. RESULTS: Adherence measures were 78% (910/1,173) for hand hygiene and 82% (223/273) for scrubs. Culture compliance was 67% (306/460). No differences were observed in bacterial hand burden or in HCWs with unique positive scrub cultures. No difference in vancomycin-resistant enterococci (VRE) and gram-negative rod (GNR) burden was observed. A difference in mean log methicillin-resistant Staphylococcus aureus (MRSA) CFU count was found between study and control scrubs for leg cargo pocket (mean log CFUs, 11.84 control scrub vs 6.71 study scrub; [Formula: see text]), abdominal area (mean log CFUs, 11.35 control scrub vs 7.54 study scrub; [Formula: see text]), leg cargo pocket at the beginning of shift (mean log CFUs, 11.96 control scrub vs 4.87 study scrub; [Formula: see text]), and abdominal area pocket at the end of shift (mean log CFUs, 12.14 control scrubs vs 8.22 study scrub; [Formula: see text]). CONCLUSIONS: Study scrubs were associated with a 4-7 mean log reduction in MRSA burden but not VRE or GNRs. A prospective trial is needed to measure the impact of antimicrobial impregnated apparel on MRSA transmission rates. PMID- 22314065 TI - The impact of depth of infection and postdischarge surveillance on rate of surgical-site infections in a network of community hospitals. AB - OBJECTIVE: To describe the epidemiology of surgical-site infections (SSIs) in community hospitals and to explore the impact of depth of SSI, healthcare location at the time of diagnosis, and variations in surveillance practices on the overall rate of SSI. DESIGN: Retrospective cohort study. SETTING: Thirty seven community hospitals in the southeastern United States. PATIENTS: Consecutive sample of patients undergoing surgical procedures between July 1, 2007, and December 31, 2008. METHODS: ANOVA was used to compare rates of SSIs, and the F test was used to compare the distribution of rates of SSIs. Wilcoxon Signed Rank test [corrected] was used to test for differences in performance rankings of hospitals. RESULTS: Following 177,706 surgical procedures, 1,919 SSIs were identified (incidence, 1.08 per 100 procedures). Sixty-four percent (1,223 of 1,919) of these were identified as complex SSIs; 87% of the complex SSIs were diagnosed in inpatient settings. The median proportion of superficial-incisional SSIs was 37% (interquartile range, 29.6%-49.5%). Postdischarge SSI surveillance was variable, with 58% of responding hospitals using surgeon letters. As reporting focus was narrowed from all SSIs to complex SSIs (incidence, 0.69 per 100 procedures) and, finally, to complex SSIs diagnosed in the inpatient setting (incidence, 0.51 per 100 procedures), variance in rates changed significantly ([Formula: see text]). Performance ranking of individual hospitals, based on rates of SSIs, differed significantly, depending on the reporting method utilized ([Formula: see text]). CONCLUSIONS: Inconsistent reporting methods focused on variable depths of infection and healthcare location at time of diagnosis significantly impact rates of SSI, distribution of rates of SSI, and hospital comparative-performance rankings. We believe that public reporting of SSI rates should be limited to complex SSIs diagnosed in the inpatient setting. PMID- 22314067 TI - Nosocomial influenza in a pediatric hospital: comparison of rates of seasonal and pandemic 2009 influenza A/H1N1 infection. AB - The rates of nosocomial seasonal (January 2008 to March 2009) and 2009 A/H1N1 (April 2009 to December 2010) influenza infections in a children's hospital were compared. Droplet precautions were used. The rates were similar during both periods, suggesting that use of droplet precautions did not result in a higher rate of influenza A/H1N1 infection. PMID- 22314066 TI - Prevalence of healthcare-associated infections in acute care hospitals in Jacksonville, Florida. AB - OBJECTIVE: To determine healthcare-associated infection (HAI) prevalence in 9 hospitals in Jacksonville, Florida; to evaluate the performance of proxy indicators for HAIs; and to refine methodology in preparation for a multistate survey. DESIGN: Point prevalence survey. PATIENTS: Acute care inpatients of any age. METHODS: HAIs were defined using National Healthcare Safety Network criteria. In each facility a trained primary team (PT) of infection prevention (IP) staff performed the survey on 1 day, reviewing records and collecting data on a random sample of inpatients. PTs assessed patients with one or more proxy indicators (abnormal white blood cell count, abnormal temperature, or antimicrobial therapy) for the presence of HAIs. An external IP expert team collected data from a subset of patient records reviewed by PTs to assess proxy indicator performance and PT data collection. RESULTS: Of 851 patients surveyed by PTs, 51 had one or more HAIs (6.0%; 95% confidence interval, 4.5%-7.7%). Surgical site infections ([Formula: see text]), urinary tract infections ([Formula: see text]), pneumonia ([Formula: see text]), and bloodstream infections ([Formula: see text]) accounted for 75.8% of 58 HAIs detected by PTs. Staphylococcus aureus was the most common pathogen, causing 9 HAIs (15.5%). Antimicrobial therapy was the most sensitive proxy indicator, identifying 95.5% of patients with HAIs. CONCLUSIONS: HAI prevalence in this pilot was similar to that reported in the 1970s by the Centers for Disease Control and Prevention's Study on the Efficacy of Nosocomial Infection Control. Antimicrobial therapy was a sensitive screening variable with which to identify those patients at higher risk for infection and reduce data collection burden. Additional work is needed on validation and feasibility to extend this methodology to a national scale. PMID- 22314068 TI - The cross-transmission of 2009 pandemic influenza A (H1N1) infections among healthcare workers and inpatients in a chinese tertiary hospital. AB - We reported 2009 H1N1 influenza infections among healthcare workers (HCWs) and inpatients and the prevention measures instituted in a large Chinese hospital. In total, 171 HCWs and 89 inpatients tested positive for H1N1. Sixteen HCWs had known hospital exposure, among whom only 7 had working-contact exposure. There was no influenza outbreak. PMID- 22314069 TI - Infection prevention and control guidance for Ronald McDonald Houses: a needs assessment. AB - We surveyed Ronald McDonald Houses (RMHs) to assess infection prevention and control (IPC) practices. A diverse patient population is served by RMH. Most sites have locally written IPC guidelines, and consultation resources vary, increasing the potential for inconsistent IPC practices. RMH would benefit from a standardized IPC guideline. PMID- 22314070 TI - Colonization with extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species in long-term care facility residents. AB - We describe the prevalence of and risk factors for colonization with extended spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-EB) in the long-term care facility (LTCF) setting. Colonization prevalence differed significantly across the 3 LTCFs evaluated in the study, with recent use of levofloxacin and fecal incontinence demonstrating borderline significant associations with ESBL-EB colonization. PMID- 22314071 TI - Implementing automated surveillance for tracking Clostridium difficile infection at multiple healthcare facilities. AB - Automated surveillance using electronically available data has been found to be accurate and save time. An automated Clostridium difficile infection (CDI) surveillance algorithm was validated at 4 Centers for Disease Control and Prevention Epicenter hospitals. Electronic surveillance was highly sensitive, specific, and showed good to excellent agreement for hospital-onset; community onset, study facility-associated; indeterminate; and recurrent CDI. PMID- 22314072 TI - Surveillance of device-associated infections in intensive care units in South Brazil. PMID- 22314074 TI - Hydrogen peroxide vapor and aerosol room decontamination systems. PMID- 22314075 TI - Analysis of hip and knee arthroplasty surgical site infection data in Western Australia: null effect of stratification by procedure type. PMID- 22314076 TI - Universal methicillin-resistant Staphylococcus aureus (MRSA) screening: comparison of anatomic screening sites for patients with high and low prevalence of MRSA carriage. PMID- 22314077 TI - TWEAK in inclusion-body myositis muscle: possible pathogenic role of a cytokine inhibiting myogenesis. AB - Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor Fn14 exert pleiotropic effects, including regulation of myogenesis. Sporadic inclusion-body myositis (IBM) is the most common muscle disease of the elderly population and leads to severe disability. IBM mesoangioblasts, different from mesoangioblasts in other inflammatory myopathies, display a myogenic differentiation defect. The objective of the present study was to investigate TWEAK-Fn14 expression in IBM and other inflammatory myopathies and explore whether TWEAK modulation affects myogenesis in IBM mesoangioblasts. TWEAK, Fn14, and NF-kappaB expression was assessed by immunohistochemistry and Western blot in cell samples from both muscle biopsies and primary cultures. Mesoangioblasts isolated from samples of IBM, dermatomyositis, polymyositis, and control muscles were treated with recombinant human TWEAK, Fn14-Fc chimera, and anti-TWEAK antibody. TWEAK-RNA interference was performed in IBM and dermatomyositis mesoangioblasts. TWEAK levels in culture media were determined by enzyme-linked immunosorbent assay. In IBM muscle, we found increased TWEAK-Fn14 expression. Increased levels of TWEAK were found in differentiation medium from IBM mesoangioblasts. Moreover, TWEAK inhibited myogenic differentiation of mesoangioblasts. Consistent with this evidence, TWEAK inhibition by Fn14-Fc chimera or short interfering RNA induced myogenic differentiation of IBM mesoangioblasts. We provide evidence that TWEAK is a negative regulator of human mesoangioblast differentiation. Dysregulation of the TWEAK-Fn14 axis in IBM muscle may induce progressive muscle atrophy and reduce activation and differentiation of muscle precursor cells. PMID- 22314078 TI - Invertebrate neuropeptides XII. PMID- 22314079 TI - Plasma level of calcitonin gene-related peptide in patients with polycystic ovary syndrome and its relationship to hormonal and metabolic parameters. AB - The aim of the study was to evaluate the plasma level of calcitonin gene-related peptide (CGRP) in patients with polycystic ovary syndrome (PCOS) and its relationship to hormonal and metabolic parameters. We also observed the effect of CGRP on testosterone (T) and estradiol (E(2)) release in cultured human granulosa cells. PCOS subjects (n=215) and matched healthy control women (n=103) at age of 22-38 years were enrolled in this study. We analyzed plasma CGRP concentrations, relationship of plasma CGRP with insulin resistance (IR), body mass index (BMI), luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio and T. The T and E(2) release levels of cultured human granulosa cells treated by CGRP were also measured. The results showed that plasma CGRP concentrations were significantly higher in women with PCOS than those of control subjects. In women with PCOS, there was a strong positive correlation between the plasma CGRP level with HOMA IR, AUC-insulin, AUC-glucose, the ratio of LH/FSH and plasma T concentration. Human granulosa cells expressed CGRP receptor. Exogenous CGRP caused an elevation of T and E(2) released from the human granulosa cells. These findings suggest that CGRP may participate in the pathophysiological process of PCOS. PMID- 22314080 TI - Natural and synthetic chiral isoforms of crustacean hyperglycemic hormone from the crayfish Astacus leptodactylus: hyperglycemic activity and hemolymphatic clearance. AB - In the crayfish Astacus leptodactylus, as in several crustacean species, the crustacean hyperglycemic hormone is present as two isoforms differing by the chirality of the third residue, a phenylalanine. In the present work, isoforms synthesized full length by solid-phase peptide synthesis have been purified, refolded, the location of the disulfide bridges has been checked, their immunoreactivity against different antibodies have been analyzed and their hyperglycemic activity tested, to ensure the identity of the synthetic peptides with their natural homologs. Different parameters of the hyperglycemic activity of both isoforms were studied. In addition to a difference in the kinetics of hyperglycemia, already known from other studies, it was observed that the dose response was different depending on the season where experiments were performed, the response being stronger in spring than in autumn, especially for the d-Phe containing isoform. A dosage method based on sandwich enzyme linked immunosorbent assay (ELISA) has been developed to measure hemolymphatic levels of the isoforms after spiking of the animals with one isoform or the other. It was found that hemolymphatic clearance was identical for both isoforms, indicating that their differential effect is not linked to their different lifetime in the hemolymph but may rather rely on other mechanisms such as their binding to different target tissues. PMID- 22314081 TI - Comprehensive report on prostate cancer misclassification by 16 currently used low-risk and active surveillance criteria. AB - What's known on the subject? and What does the study add? Prostate cancer characterisation, based on laboratory findings, clinical examination and histopathological cancer features that are used to define selection criteria for AS, is not ideal. Consequently, a panel of strict or more lenient criteria to select patients for AS have been published. Studies investigating the relationship between pretreatment variables and final pathology have been done in the past showing the risk of cancer misclassification for some criteria. No study has presented an overview of cancer selection using a panel of 16 currently used AS criteria that is presented in the present study. In an exactly defined cohort after radical prostatectomy, each set of criteria was used as a diagnostic test to separate between patients with more favourable (pT2, no Gleason upgrade between biopsy grading and final pathology) and unfavourable cancer features (pT3, pN+, Gleason upgrade). To the best of our knowledge a comparison of test quality criteria for AS criteria given by sensitivity, specificity, positive and negative predictive value and likelihood ratio has not yet been reported. Moreover, we showed that tumour characterisation, by a formally sufficient 12 core biopsy, in the present dataset harboured a risk of ~20% that unfavourable cancer features were missed regardless of whether strict or more lenient selection criteria for AS were chosen. OBJECTIVE: To evaluate final histopathological features among men diagnosed with prostate cancer eligible for low-risk (LR) or active surveillance (AS) criteria. PATIENTS AND METHODS: Retrospective application of 16 definitions for AS or LR prostate cancer to a contemporary (January 2008 to March 2011) open retropubic radical prostatectomy (RRP) series of 1745 patients. EXCLUSION CRITERIA: neoadjuvant hormones, radiotherapy, inadequate histopathological reports, <10 biopsy cores. Report on the number of men with insignificant tumours (defined as: <=pT2, Gleason score <=6, tumour volume <0.5 mL) and men who had unfavourable tumour characteristics on final pathology (defined as: extracapsular extension or seminal vesicle invasion or lymph node metastasis or Gleason upgrading). Sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPV) were calculated. RESULTS: Eligibility of patients in the final study cohort (n = 1070) varied from 5.1% to 92.7% depending on the AS or LR criteria used. Final pathology revealed 77 insignificant cancers and 578 patients who had unfavourable histopathological criteria. The detection rate for insignificant cancers on final pathology was variable ranging from 7.8% to 28.3% depending on the AS- or LR prediction tool used; unfavourable tumour characteristics were found in up to 33.5% on final pathology. The sensitivity, specificity, PPV and NPV were 8.5 97.9%, 24.7-97.8%, 67.7-89.1% and 45.3-78.2%, respectively. The likelihood ratio to correctly identify a patient with LR disease on final pathology ranged from 1.3 to 8. CONCLUSIONS: AS or LR criteria have a significant risk of cancer misclassification. Better prediction tools are needed to improve these criteria. Re-biopsy might improve safety and should be considered more frequently in patients who opt for AS. PMID- 22314082 TI - Contribution of CXCL12 secretion to invasion of breast cancer cells. AB - INTRODUCTION: Neu (HER2/ErbB2) is overexpressed in 25% to 30% of human breast cancer, correlating with a poor prognosis. Researchers in previous studies who used the mouse mammary tumor virus Neu-transgenic mouse model (MMTV-Neu) demonstrated that the Neu-YB line had increased production of CXCL12 and increased metastasis, whereas the Neu-YD line had decreased metastasis. In this study, we examined the role of increased production of CXCL12 in tumor cell invasion and malignancy. METHODS: We studied invasion in the tumor microenvironment using multiphoton intravital imaging, in vivo invasion and intravasation assays. CXCL12 signaling was altered by using the CXCR4 inhibitor AMD3100 or by increasing CXCL12 expression. The role of macrophage signaling in vivo was determined using a colony-stimulating factor 1 receptor (CSF-1R) blocking antibody. RESULTS: The Neu-YD strain was reduced in invasion, intravasation and metastasis compared to the Neu-YB and Neu deletion mutant (activated receptor) strains. Remarkably, in the Neu-YB strain, in vivo invasion to epidermal growth factor was dependent on both CXCL12-CXCR4 and CSF1-CSF-1R signaling. Neu-YB tumors had increased macrophage and microvessel density. Overexpression of CXCL12 in rat mammary adenocarcinoma cells increased in vivo invasion as well as microvessel and macrophage density. CONCLUSIONS: Expression of CXCL12 by tumor cells results in increased macrophage and microvessel density and in vivo invasiveness. PMID- 22314083 TI - MAVIDOS Maternal Vitamin D Osteoporosis Study: study protocol for a randomized controlled trial. The MAVIDOS Study Group. AB - MAVIDOS is a randomised, double-blind, placebo-controlled trial (ISRCTN82927713, registered 2008 Apr 11), funded by Arthritis Research UK, MRC, Bupa Foundation and NIHR. BACKGROUND: Osteoporosis is a major public health problem as a result of associated fragility fractures. Skeletal strength increases from birth to a peak in early adulthood. This peak predicts osteoporosis risk in later life. Vitamin D insufficiency in pregnancy is common (31% in a recent Southampton cohort) and predicts reduced bone mass in the offspring. In this study we aim to test whether offspring of mothers supplemented with vitamin D in pregnancy have higher bone mass at birth than those whose mothers were not supplemented. METHODS/DESIGN: Women have their vitamin D status assessed after ultrasound scanning in the twelfth week of pregnancy at 3 trial centres (Southampton, Sheffield, Oxford). Women with circulating 25(OH)-vitamin D levels 25-100 nmol/l are randomised in a double-blind design to either oral vitamin D supplement (1000 IU cholecalciferol/day, n = 477) or placebo at 14 weeks (n = 477). Questionnaire data include parity, sunlight exposure, dietary information, and cigarette and alcohol consumption. At 19 and 34 weeks maternal anthropometry is assessed and blood samples taken to measure 25(OH)-vitamin D, PTH and biochemistry. At delivery venous umbilical cord blood is collected, together with umbilical cord and placental tissue. The babies undergo DXA assessment of bone mass within the first 14 days after birth, with the primary outcome being whole body bone mineral content adjusted for gestational age and age. Children are then followed up with yearly assessment of health, diet, physical activity and anthropometric measures, with repeat assessment of bone mass by DXA at age 4 years. DISCUSSION: As far as we are aware, this randomised trial is one of the first ever tests of the early life origins hypothesis in human participants and has the potential to inform public health policy regarding vitamin D supplementation in pregnancy. It will also provide a valuable resource in which to study the influence of maternal vitamin D status on other childhood outcomes such as glucose tolerance, blood pressure, cardiovascular function, IQ and immunology. PMID- 22314084 TI - Acceptability and compliance of atenolol tablet, compounded paste and compounded suspension prescribed to healthy cats*. AB - This study was designed to evaluate the cats' acceptance and compliance of the owners and cats towards an extemporaneously prepared palatable compounded atenolol (paste and suspension) formulation in comparison to the commercially obtained tablet, in a randomised, cross-over study design.The three formulations were prescribed twice daily for 6 days to 13 healthy privately-owned cats of 13 different owners, with varying levels of experience in medicating cats. Daily compliance was evaluated via an owner-completed diary, completed after each dose administered. Owner's experience and preference of the formulation was evaluated via questionnaires given prior to, at the end of each treatment protocol, and upon completion of the study. Although compounded suspension was association with fewest missed doses, the majority of cat owners expressed a preference for the divided tablet. Atenolol tablets, compounded paste and suspension acceptance and compliance were comparable. Further work is now required to assess the amount and stability of the active ingredient and the robustness of the paste and suspension formulations prior to any bioavailability comparisons between the formulations. PMID- 22314085 TI - Clinical efficacy of the acyclic nucleoside phosphonate 9-(2 phosphonylmethoxypropyl)-2,6-diaminopurine (PMPDAP) in the treatment of feline immunodeficiency virus-infected cats. AB - In in vitro studies, the acyclic nucleoside phosphonate 9-(2 phosphonylmethoxypropyl)-2,6-diaminopurine (PMPDAP) inhibited the replication of feline immunodeficiency virus (FIV). No information about its clinical efficacy is available so far. The aim of this prospective placebo-controlled, double blinded study was to evaluate the antiviral efficacy of PMPDAP in cats naturally infected with FIV. Twenty cats were randomly assigned to two treatment groups receiving either PMPDAP (25 mg/kg) or placebo twice per week subcutaneously for 6 weeks. The general health status (Karnofsky's score), clinical signs, laboratory, immunological, and surrogate parameters were evaluated. No significant differences were found between PMPDAP- and placebo-treated cats, although cats treated with PMPDAP showed a tendency for improvement in their Karnofsky's score and clinical signs. Haematological side effects were noted in the PMPDAP-treated cats. Thus, PMPDAP may be an option in treating cats if it becomes available for veterinarians, but side effects have been monitored. PMID- 22314086 TI - Cryptosporidium species screening using Kinyoun technique in domestic cats with diarrhea. AB - Cryptosporidium is a coccidian that can lead to diarrhea, especially in immunosuppressed individuals. Retroviruses are considered a primary cause of immunosuppression in cats. Fecal specimens and blood collected from the 60 cats were evaluated for the presence of acid-fast cryptosporidia in three consecutive stool samples and for feline leukemia virus (FeLV) antigen and feline immunodeficiency virus (FIV) antibody by ELISA testing. Five animals (8.33%) shedding oocysts were found, one was both FIV- and FeLV-negative and four were FeLV-positive. PMID- 22314087 TI - Effects of maternally-derived antibodies on serologic responses to vaccination in kittens. AB - The optimal vaccination protocol to induce immunity in kittens with maternal antibodies is unknown. The objective of this study was to determine the effects of maternally-derived antibody (MDA) on serologic responses to vaccination in kittens. Vaccination with a modified live virus (MLV) product was more effective than an inactivated (IA) product at inducing protective antibody titers (PAT) against feline panleukopenia virus (FPV). IA vaccination against feline herpesvirus-1 (FHV) and feline calicivirus (FCV) was more effective in the presence of low MDA than high MDA. Among kittens with low MDA, MLV vaccination against FCV was more effective than IA vaccination. A total of 15%, 44% and 4% of kittens had insufficient titers against FPV, FHV and FCV, respectively, at 17 weeks of age. Serologic response to vaccination of kittens varies based on vaccination type and MDA level. In most situations, MLV vaccination should be utilized and protocols continued beyond 14 weeks of age to optimize response by all kittens. PMID- 22314088 TI - Histology and morphometry of the testes of adult domestic cats (Felis catus). AB - Testicles of 30 mongrel cats were analyzed histologically and morphometrically, divided into three groups: G1 (1-2 years old), G2 (over 2 and up to 4 years old) and G3 (over 4 and up to 6 years old). After orchiectomy and histopathology, the morphometric parameters studied were: thickness of the tunica albuginea (72 MUm) and seminiferous epithelium (77.19 MUm), perimeter (53.81; 90.57 MUm), (54.80; 101.07 MUm); area (174.23; 494.55 MUm(2)), (176.68; 629.70 MUm(2)); maximum diameter (14.94; 28.02 MUm), (14.76; 31.66 MUm); minimum diameter (13.25; 21.92 MUm), (13.30; 24.52 MUm); and shape factor (index for regularity of the format) (1.36; 1.36), (1.39; 1.35) of the nucleus and cytoplasm of spermatogonia and Leydig cells, respectively. The results can be used for comparative studies and contribute knowledge concerning the height of the seminiferous epithelium, thickness of the tunica albuginea and size of spermatogonia and Leydig cells. PMID- 22314089 TI - Pancreatic rupture in four cats with high-rise syndrome. AB - Pancreatic trauma and rupture are rare after feline high-rise syndrome; however, should it happen, pancreatic enzymes will leak into the abdominal cavity and may cause pancreatic autodigestion and fatty tissue saponification. If not diagnosed and treated, it can ultimately lead to multiorgan failure and death. In this case series, 700 records of high-rise syndrome cats that presented between April 2001 and May 2006 were analysed, and four cats with pancreatic rupture were identified. Clinical signs, diagnosis using ultrasonography and lipase activity in blood and abdominal effusion, and treatment modalities are reported. Three cats underwent surgical abdominal exploration, one cat was euthanased. Rupture of the left pancreatic limb was confirmed in all cases. Two of the operated cats survived to date. High-rise syndrome can lead to abdominal trauma, including pancreatic rupture. A prompt diagnosis and surgical treatment should be considered. PMID- 22314090 TI - Analytical performance of commercially-available assays for feline insulin-like growth factor 1 (IGF-1), adiponectin and ghrelin measurements. AB - The objective of this study was to evaluate three commercially-available human assays for the determination of adiponectin, ghrelin and insulin-like growth factor 1 (IGF-1) concentrations in feline serum samples. Intra- and interassay coefficients of variation were lower than 20%, 15% and 6% for adiponectin, ghrelin and IGF-1 assays, respectively. Dilutions of feline serum pools resulted in linear regression equations in all kits. Mean recovery of adiponectin, ghrelin and IGF-1 assays were 107%, 102% and 105%, respectively. Significant differences were detected in adiponectin and ghrelin concentrations between lean and obese cats (P <0.05 in both cases), but there was no difference in IGF-1 concentrations (P = 0.12). PMID- 22314091 TI - Amputation for histiocytic sarcoma in a cat. AB - A 9-year-old spayed female domestic shorthair cat presented with a skin lesion of the left tarsus. The lesion was biopsied and, based on the microscopic appearance and immunohistochemical characteristics, histiocytic sarcoma was diagnosed. Amputation was performed with improved demeanor seen postoperatively. However, between 44 and 60 days following the surgery, relapse of skin lesions appeared in multiple locations, including at the previous amputation site, and euthanasia was elected. This is the first report of a histiocytic sarcoma treated with amputation in a cat. PMID- 22314092 TI - Open surgical correction combined with an external splint for correction of a non compliant pectus excavatum in a cat. AB - A 4-month-old domestic shorthair female cat weighing 1.3 kg was presented for evaluation of respiratory distress. The animal showed evident dyspnoea with exercise intolerance and a marked concave deformation of the sternum. After measurements of the fronto-sagittal and vertebral indexes, the pectus was classified as moderate and surgery was elected. Surgical correction was performed using an open approach to the sternum with osteotomy of the last sternebra and costochondral junctions of the eighth and ninth ribs bilaterally. A silicone based, U-shape external splint was manufactured and used to stabilise the sternum. Immediate and 5-week postsurgical radiographs revealed a decreased concavity of the sternum and an increase thoracic height at the level of the last sternebra. Postoperative results suggest that this technique could be an effective and economical option for cats with pectus excavatum with a non compliant sternum. PMID- 22314093 TI - Spinal cord trauma in a cat caused by ingestion of a splinter. AB - A 5-month-old male Abyssinian presented with right hemiplegia. Cervical radiographs, haematology and serum biochemistry were normal. A foreign body was identified on computed tomography (CT) and magnetic resonance imaging (MRI). Removal of the foreign body was carried out via a dorsal approach between the occipital bone and the C1 vertebral body using intra-operative CT. No complications were encountered. Thirty days after surgery, the cat was ambulatory. PMID- 22314094 TI - Successful treatment of hepatic failure secondary to diazepam administration in a cat. AB - A 2-year-old castrated male domestic shorthair cat developed acute hepatic failure following oral diazepam administration for behavioral problems. The patient survived with intensive supportive care and was discharged after 5 days in hospital. Successful treatment of diazepam-associated fulminant hepatic failure in cats has rarely been described in the veterinary literature. PMID- 22314095 TI - Feline panleukopenia virus, feline herpesvirus-1 and feline calicivirus antibody responses in seronegative specific pathogen-free kittens after parenteral administration of an inactivated FVRCP vaccine or a modified live FVRCP vaccine. AB - Two groups of feline panleukopenia (FPV), feline calicivirus (FCV) and feline herpesvirus 1 (FHV-1) seronegative kittens (six cats per group) were administered one of two feline viral rhinotracheitis, calcivirus and panleukopenia (FVRCP) vaccines subcutaneously (one inactivated and one modified live) and the serological responses to each agent were followed over 49 days (days 0, 2, 5, 7, 10, 14, 21, 28, 35, 42, 49). While the kittens administered the modified live FPV vaccine were more likely to seroconvert on day 7 after the first inoculation than kittens administered the inactivated vaccine, all kittens had seroconverted by day 14. In contrast, FHV-1 serological responses were more rapid following administration of the inactivated FVRCP vaccine when compared with the modified live FVRCP vaccine. There were no statistical differences between the serological response rates between the two FVRCP vaccines in regard to FCV. PMID- 22314096 TI - In vitro comparison of feline bone marrow-derived and adipose tissue-derived mesenchymal stem cells. AB - Mesenchymal stem cells (MSC) are increasingly being proposed as a therapeutic option for a variety of different diseases in human and veterinary medicine. At present, MSC are most often collected from bone marrow (BM) or adipose tissue (AT) and enriched and expanded in vitro before being transferred into recipients. However, little is known regarding the culture characteristics of feline BM derived (BM-MSC) versus AT-derived MSC (AT-MSC). We compared BM-MSC and AT-MSC from healthy cats with respect to in vitro growth and cell surface phenotype. Mesenchymal stem cells isolated from AT proliferated significantly faster than BM MSC. Phenotypic differences between BM-MSC and AT-MSC were not present in the surface markers assessed. We conclude that BM-MSC and AT-MSC are similar phenotypically but that cultures of AT-MSC are easier to generate because of their higher intrinsic proliferative rate. Thus, AT-MSC may be the preferred MSC for clinical applications where rapid and efficient generation of MSC is important. PMID- 22314097 TI - Laparoscopic-assisted incisional colopexy by two portals access in a domestic cat with recurrent rectal prolapse. AB - A 2-year-old female mixed-breed cat weighing 2.7 kg presented with recurrent rectal prolapse. The following report describes its treatment by laparoscopic assisted incisional colopexy using two portals. The procedure was effective and without trans- or postoperative complications. Recurrent prolapses did not recur in the 2 months of postoperative observation. PMID- 22314098 TI - Quarantine protects Falkland Islands (Malvinas) cats from feline coronavirus infection. AB - Feline coronavirus (FCoV) causes feline infectious peritonitis (FIP). Since 2002, when 20 cats on the Falkland Islands were found to be FCoV seronegative, only seronegative cats could be imported. Between 2005-2007, 95 pet and 10 feral cats tested negative by indirect immunofluorescence antibody (IFA) analysis using two strains of type II FCoV, two transmissible gastroenteritis virus assays, an enzyme-linked immunosorbent assay and rapid immunomigration test. Twenty-four samples (23%) showed non-specific fluorescence, mostly attributable to anti nuclear antibodies (ANA). The reason for ANA was unclear: reactive samples were negative for Erhlichia canis antibodies; seven were feline immunodeficiency virus positive, but 15 were negative. It was not possible to determine retrospectively whether the cats had autoimmune disease, hyperthyroidism treatment, or recent vaccination which may also cause ANA. The FCoV/ FIP-free status of the Falkland Islands cats should be maintained by FCoV testing incoming cats. However, ANA can complicate interpretation of IFA tests. PMID- 22314099 TI - Collaborative approaches to anticancer drug discovery and development: a Cancer Research UK perspective. AB - The pharmaceutical industry is under huge pressure to overhaul what is currently viewed as a highly inefficient operating model. Unacceptable levels of late-stage failure in clinical development remain a fundamental problem for the sector. Lack of efficacy is a major reason for candidate failure and a lack of understanding of disease biology is considered to be a key issue underpinning this problem. There has been a recent upsurge in interest from pharmaceutical and biotechnology companies to collaborate with academic institutions, with the latter viewed as being home to research teams with in-depth biological knowledge and translational research expertise. This article outlines models for collaboration in drug discovery and development being pursued by the research-based charity Cancer Research UK (CR-UK). PMID- 22314100 TI - Cancer cell senescence: a new frontier in drug development. AB - Senescence forms a universal block to tumorigenesis which impacts on all hallmarks of cancer, making it an attractive target for drug discovery. Therefore a strategy must be devised to focus this broad potential into a manageable drug discovery programme. Several issues remain to be addressed including the lack of robust senescence-inducing compounds and causally related biomarkers to measure cellular response. Here, we review the latest progress in translating senescence as a target for cancer therapy and some promising approaches to drug and biomarker discovery. Finally, we discuss the potential application of a senescence-induction therapy in a clinical setting. PMID- 22314101 TI - A placebo-controlled trial of Korean red ginseng extract for preventing influenza like illness in healthy adults. AB - BACKGROUND: Standardized Korean red ginseng extract has become the best-selling influenza-like illness (ILI) remedy in Korea, yet much controversy regarding the efficacy of the Korean red ginseng (KRG) in reducing ILI incidence remains. The aim of the study is to assess the efficacy of the KRG extract on the ILI incidence in healthy adults. METHODS/DESIGN: We will conduct a randomized, double blind, placebo-controlled study at the onset of the influenza seasons. A total of 100 subjects 30-70 years of age will be recruited from the general populations. The subjects will be instructed to take 9 capsules per day of either the KRG extract or a placebo for a period of 3 months. The primary outcome measure is to assess the frequency of ILI onset in participated subjects. Secondary variable measures will be included severity and duration of ILI symptoms. The ILI symptoms will be scored by subjects using a 4-point scale. DISCUSSION: This study is a randomized placebo controlled trial to evaluate the efficacy of the KRG extract compared to placebo and will be provided valuable new information about the clinical and physiological effects of the KRG extract on reduction of ILI incidence including flu and upper respiratory tract infections. The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if KRG extract can be shown to be an effective reduction strategy in ILI incidence. TRIAL REGISTRATION: NCT01478009. PMID- 22314102 TI - Effects of combination of leaf resources on competition in container mosquito larvae. AB - Resource diversity is critical to fitness in many insect species, and may determine the coexistence of competitive species and the function of ecosystems. Plant material provides the nutritional base for numerous aquatic systems, yet the consequences of diversity of plant material have not been studied in aquatic container systems important for the production of mosquitoes. To address how diversity in leaf detritus affects container-inhabiting mosquitoes, we examined how leaf species affect competition between two container inhabiting mosquito larvae, Aedes aegypti and Aedes albopictus, that co-occur in many parts of the world. We tested the hypotheses that leaf species changes the outcome of intra- and interspecific competition between these mosquito species, and that combinations of leaf species affect competition in a manner not predictable based upon the response to each leaf species alone (i.e. the response to leaf combinations is non-additive). We find support for our first hypothesis that leaf species can affect competition, evidence that, in general, leaf combination alters competitive interactions, and no support that leaf combination impacts interspecific competition differently than intraspecific competition. We conclude that combinations of leaves increase mosquito production non-additively such that combinations of leaves act synergistically, in general, and result in higher total yield of adult mosquitoes in most cases, although certain leaf combinations for A. albopictus are antagonistic. We also conclude that leaf diversity does not have a different effect on interspecific competition between A. aegypti and A. albopictus, relative to intraspecific competition for each mosquito. PMID- 22314103 TI - Concordant promoter methylation of transforming growth factor-beta receptor types I and II occurs early in esophageal squamous cell carcinoma. AB - INTRODUCTION: Transforming growth factor-beta (TGF-beta) is a pleiotropic growth factor with multiple functions through its type I (TGFBR1) and type II (TGFBR2) receptors. A reduction or loss of expression of TGFBRs enables cancer cells to escape the growth inhibitory effect of TGF-beta and to gain a growth advantage. OBJECTIVE: The promoter methylation status and expression of TGFBR1, TGFBR2 and Smad4 gene were investigated in esophageal squamous cell carcinoma (ESCC). DESIGN: Methylation-specific polymerase chain reaction approach was used to detect the methylation status. Immunohistochemistry and reverse transcription polymerase chain reaction method were used to examine the protein and messenger RNA expression, respectively. RESULTS: Both the ESCC and the high-grade dysplastic tissues showed hypermethylation of TGFBR1 and TGFBR2, and the hyper methylation of TGFBR1 and TGFBR2 in ESCC tissues was significantly associated with decreased messenger RNA and protein expression (P < 0.05). When stratified for tumor lymph node metastasis stages, TGFBR1 and TGFBR2 gene methylation was more frequent in stage III and stage IV tumor tissues than that in stage I and stage II tumor tissues (P < 0.05). Simultaneous methylation of the 2 receptors was progressively increased along with the increasing of tumor lymph node metastasis stage and decreasing of histological differentiation. Smad4 hypermethylation was only detected in 7 ESCC tumor tissues and associated with the loss of Smad4 expression. The decreased protein expression of TGFBR1, TGFBR2 and Smad4 was correlated with increased expression of TGF-beta1 in ESCC. CONCLUSIONS: These data suggest that promoter methylation of TGFBR1 and TGFBR2 may exist in the early stage of ESCC and play important roles in TGFBR1 and TGFBR2 gene silencing. PMID- 22314104 TI - Does the relationship between natriuretic hormones and diastolic function differ by race? AB - INTRODUCTION: Heart failure develops earlier and is more prevalent in blacks than whites because of their higher incidence of hypertension and diabetes and likely subsequent diastolic dysfunction. Natriuretic peptides (NP) prevent cardiac malfunction through pressure, natriuresis action. However, whether race affects the relationships of NP action with cardiac function is unknown. METHODS: To assess this, 55 (21 whites and 27 males) normotensive adults underwent a 2-hour protocol of 40 minutes rest, video game stressor and recovery. Mitral inflow and myocardial velocities (tissue Doppler) were recorded every 20 minutes. Blood pressure and heart rate were obtained at 10-minute intervals. Blood samples for pro-atrial NP and pro-brain NP (pro-BNP) were collected every 40 minutes. RESULTS: There were differences in the association between (1) the changes from rest to stress for E/A ratio and double product (whites, r = -0.42; blacks, r = 0. 10; P = 0.034 for difference between correlations); (2) stress E(m) and pro atrial NP (whites, r = 0.59; blacks, r = -0.25; P = 0.025); (3) rest E(m) and BNP (whites, r = 0.83; blacks r = -0.17; P = 000); (4) rest E(m)/A(m) and pro-BNP (whites, r = 0.70; blacks, r = -0.42; P = 0.003); (5) rest E/E(m) and pro-BNP (whites, r = -0.61; blacks, r = 0.31; P = 0.015) and (6) stress E and pro-BNP (whites, r = 0.56; blacks, r = -0.18; P = 0.043). CONCLUSION: The higher correlations between levels of NP and diastolic function indices both at rest and stress suggest that NP protective action is more pronounced in whites than in blacks. PMID- 22314105 TI - Warfarin management using point-of-care testing in a university-based internal medicine resident clinic. AB - INTRODUCTION: The primary endpoint was to determine whether point-of-care (POC) International Normalization Ratio (INR) testing would increase the percentage of patients in the therapeutic range. The secondary endpoint was to determine how POC Testing (POCT) would affect the time to intervention (the amount of time it took to contact a patient who had an INR outside the therapeutic range and make the appropriate warfarin adjustment). METHODS: Over an 11-month time period, the authors implemented an anticoagulation-focused quality improvement initiative based on the internal medicine resident continuity clinic. The initiative was designed as a single site before and after study. RESULTS: The proportion of INR values within the therapeutic range before the implementation of POCT (predesign phase) was 25%. After the implementation of POCT (postdesign phase), the percentage of therapeutic INR was 50% (P = 0.005). The time to intervention in the predesign phase was 4 days while intervention was accomplished during the same visit that the blood was sampled in the postdesign phase of this study. The number needed to treat was 4 to obtain a therapeutic INR. CONCLUSION: The results of this quality improvement study showed significant improvement in the percentage of patients who were in the therapeutic range with the use of POCT. Time to intervention was also markedly improved with the addition of POCT. The authors believe that this is the first study showing such results in an internal medicine academic clinic. PMID- 22314106 TI - Cryptococcus gattii: an emerging fungal pathogen in the Southeastern United States. AB - The authors present a case of severe meningoencephalitis with cryptococcomas and hydrocephalus due to Cryptococcus gattii of the molecular type VGI in an otherwise healthy man native to Southwest Georgia without any history of travel. Clinicians need to be aware of this fungal emerging pathogen in the Southern United States. PMID- 22314107 TI - Successful daptomycin treatment for Staphylococcus lugdunensis endocarditis. AB - Staphylococcus lugdunensis, a coagulase-negative Staphylococcus species, is an increasingly relevant pathogen in the clinical setting. The organism has been isolated as a source of multiple clinical manifestations, including endocarditis. Herein, the authors present 2 cases of Staphylococcus lugdunensis endocarditis. These cases demonstrate the enhanced virulence and wide range of disease severity this organism creates. This enhanced virulence, undoubtedly present in these cases, led to novel daptomycin antibiotic regimen. To the best of the authors knowledge, these are the first reported cases using daptomycin in the treatment of Staphylococcus lugdunensis endocarditis. PMID- 22314108 TI - Luminescence properties of individual empty and water-filled single-walled carbon nanotubes. AB - The influence of water filling on the photoluminescence (PL) properties of SWCNTs is studied by ensemble and single-molecule PL spectroscopy. Red-shifted PL and PL excitation spectra are observed upon water filling for 16 chiralities and can be used to unambiguously distinguish empty SWCNTs from filled ones. The effect of water filling on the optical transitions is well-reproduced by a continuum dielectric constant model previously developed to describe the influence of the nanotube outer environment. Empty nanotubes display narrower luminescence lines and lower inhomogeneous broadening, signatures of reduced extrinsic perturbations. The radial breathing mode phonon sideband is clearly observed in the PL spectrum of small diameter empty tubes, and a strong exciton-phonon coupling is measured for this vibration. Biexponential PL decays are observed for empty and water-filled tubes, and only the short-living component is influenced by the water filling. This may be attributed to a shortening of the radiative lifetime of the bright state by the inner dielectric environment. PMID- 22314109 TI - Effect of high doses of folic acid supplementation in early pregnancy on child neurodevelopment at 18 months of age: the mother-child cohort 'Rhea' study in Crete, Greece. AB - OBJECTIVE: To investigate whether high doses of folic acid supplementation in early pregnancy are associated with child neurodevelopment at 18 months of age. DESIGN: The study uses data from the prospective mother-child cohort 'Rhea' study. Pregnant women completed an interviewer-administered questionnaire on folic acid supplementation at 14-18 weeks of gestation. Neurodevelopment at 18 months was assessed with the use of the Bayley Scales of Infant and Toddler Development (3rd edition). Red-blood-cell folate concentrations in cord blood were measured in a sub-sample of the study population (n 58). SETTING: Heraklion, Crete, Greece, 2007-2010. SUBJECTS: Five hundred and fifty-three mother-child pairs participating in the 'Rhea' cohort. RESULTS: Sixty-eight per cent of the study participants reported high doses of supplemental folic acid use (5 mg/d), while 24 % reported excessive doses of folic acid (>5 mg/d) in early pregnancy. Compared with non-users, daily intake of 5 mg supplemental folic acid was associated with a 5-unit increase on the scale of receptive communication and a 3.5-unit increase on the scale of expressive communication. Doses of folic acid supplementation higher than 5 mg/d were not associated with additional increase in the neurodevelopmental scales. CONCLUSIONS: This is the first prospective study showing that high doses of supplementary folic acid in early pregnancy may be associated with enhanced vocabulary development, communicational skills and verbal comprehension at 18 months of age. Additional longitudinal studies and trials are needed to confirm these results. PMID- 22314110 TI - Combination treatment with atorvastatin plus niacin provides effective control of complex dyslipidemias: a literature review. AB - Patients with dyslipidemia receive a cardiovascular benefit from lowering low density lipoprotein cholesterol (LDL-C). Atorvastatin is currently one of the most effective approved medications for lowering LDL-C, and has been shown to significantly reduce cardiovascular risk in many patient groups. However, even with substantial lowering of LDL-C with atorvastatin, patients still have a residual risk for coronary heart disease. Elevated triglyceride levels and low high-density lipoprotein cholesterol (HDL-C) levels may contribute to this risk. Approved medications targeting these secondary lipid parameters include fibrates, omega-3 fatty acids, and niacin. Among these medications, niacin provides the optimal increase in HDL-C levels and has efficacy similar to the other medications in lowering triglyceride levels. However, there are challenges to adherence with niacin treatment. The most common challenge during niacin treatment is flushing, although it typically decreases with ongoing use and can be ameliorated by pretreatment with aspirin and counseling by the prescriber. A combination of atorvastatin and niacin may provide more complete normalization of the lipid profile and increased cardiovascular benefits. A literature review of the PubMed and Embase databases was conducted for clinical studies that reported on the lipid-modifying efficacy of the atorvastatin plus niacin combination. Identified studies involved patients at risk for coronary heart disease and patients with established coronary heart disease. Overall, the studies were small but indicated that atorvastatin in combination with niacin was efficacious in normalizing lipid parameters. Larger lipid studies as well as studies evaluating cardiovascular outcomes during atorvastatin plus niacin treatment are warranted. PMID- 22314111 TI - Metabolic syndrome: definition and therapeutic implications. AB - The collection of impaired glucose metabolism, central obesity, elevated blood pressure, and dyslipidemia is identified as metabolic syndrome (MetS). It is estimated that approximately 25% of the world's population has MetS. In the United States, MetS is more common in men and Hispanics, and its incidence increases with age. Metabolic syndrome increases the risk of developing cardiovascular disease and type 2 diabetes mellitus. The underlying risk factors include insulin resistance and abdominal obesity. Confusion about MetS exists in part due to the lack of a consensus definition and treatment protocol. Treatment of MetS begins with therapeutic lifestyle changes and then pharmacologic treatment of the syndrome's individual components. Effective interventions include diet modification, exercise, and use of pharmacologic agents to treat risk factors. Weight loss and increasing physical activity significantly improve all aspects of MetS. A diet that includes more fruits, vegetables, whole grains, monounsaturated fats, and low-fat dairy products will benefit most patients with MetS. Physicians can be most effective in advising patients by customizing specific lifestyle recommendations after assessing patients for the presence of risk factors. PMID- 22314112 TI - Clinical management considerations for dyslipidemia in HIV-infected individuals. AB - Dyslipidemia is common in patients with human immunodeficiency virus (HIV) and may result in significant morbidity, including coronary heart disease (CHD). Treatment of dyslipidemia in these patients is generally based on the National Cholesterol Education Program Adult Treatment Panel III goals for individuals without HIV. For individuals with >= 2 cardiovascular risk factors, the risk of CHD should be evaluated using the Framingham risk calculator and managed accordingly. Switching to an antiretroviral regimen with a favorable lipid profile should be considered before pharmacologic management if virologic suppression can be maintained. Statins are the first-choice therapy for elevated low-density lipoprotein cholesterol, but in HIV-infected individuals, special consideration must be given to drug-drug interactions, specifically those between protease inhibitors and statins. Management of dyslipidemia in HIV-infected individuals is a challenging but important aspect of chronic disease management. Additional research, specifically related to the role of chronic inflammation, is needed to better define the relationship between HIV infection and cardiovascular disease. PMID- 22314113 TI - Anticoagulation prophylaxis in orthopedic surgery: an efficiency frontier approach. AB - This study assesses the use of new anticoagulants for the prevention of venous thromboembolism (VTE) in patients undergoing elective orthopedic surgery using traditional cost-effectiveness analysis and efficiency frontier methodology. RATIONALE: Efficiency frontier methodology has the potential to systematically improve the information used in policy and decision making, though it is still relatively uncommon in health economics. Anticoagulation in elective orthopedic surgery provides a fitting and timely case study for examining the influence of choosing one methodology over another. METHODS: An economic model was developed to capture the relative benefits and consequences of choosing one anticoagulation strategy over another in the context of orthopedic surgery. Three novel oral anticoagulants (apixaban, rivaroxaban, dabigatran) are compared with enoxaparin 40 mg daily from the UK National Health Service perspective using traditional cost-effectiveness estimates (cost/quality-adjusted life years, cost/life years gained) and the efficiency frontier. The latter explicitly includes embolic and bleeding events as outcomes. A 5-year time horizon was adopted. RESULTS: Total discounted costs ranged from about L200 000 to L431 000 over 5 years per 1000 patients undergoing elective total hip arthroplasty, and from L243 000 to L463 000 per 1000 patients for elective total knee arthroplasty. Analysis of the efficiency frontier demonstrates that apixaban and rivaroxaban are the preferred choices, depending on the outcome examined and the type of surgery. In terms of safety, apixaban is associated with more bleeding events avoided; yet, rivaroxaban demonstrated better VTE outcomes. CONCLUSION: Traditional cost effectiveness analysis systematically excludes information related to the safety profiles of these anticoagulants. The efficiency frontier approach presented in this study provides critical information, without substantial effort, to permit a fully informed decision by taking into account all relevant outcomes as they relate to the costs associated with treatment choice. PMID- 22314114 TI - Current approaches to the treatment of hypertension in older persons. AB - Hypertension is a major risk factor for cardiovascular disease and is present in 69% of patients with a first myocardial infarction, in 77% of patients with a first stroke, in 74% of patients with chronic heart failure, and in 60% of patients with peripheral arterial disease. Double-blind, randomized, placebo controlled trials have demonstrated that antihypertensive drug therapy reduces cardiovascular events in patients aged 65 to 79 years. In the Hypertension in the Very Elderly Trial, patients aged >= 80 years who were treated with antihypertensive drug therapy had, at 1.8-year follow-up, a 30% reduction in fatal or nonfatal stroke (P = 0.06), a 39% reduction in fatal stroke (P = 0.05), a 21% reduction in all-cause mortality (P = 0.02), a 23% reduction in cardiovascular death (P = 0.06), and a 64% reduction in heart failure (P < 0.001). Although the optimal blood pressure (BP) treatment goal in the elderly has not been determined, existing epidemiologic and clinical trial data suggest that a reasonable therapeutic BP goal should be < 140/90 mm Hg in persons aged < 80 years and a systolic BP of 140 to 145 mm Hg if tolerated in persons aged >= 80 years. Nonpharmacologic lifestyle measures should be encouraged both to prevent development of hypertension and as adjunctive therapy in persons with hypertension. Diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and calcium channel blockers have all shown benefit in reducing cardiovascular events in randomized trials. The choice of specific drugs depends on efficacy, tolerability, presence of specific comorbidities, and cost. Adverse effects from treatment, such as electrolyte disturbances, renal dysfunction, and excessive orthostatic BP reduction, should be avoided. PMID- 22314115 TI - Chlorthalidone: the forgotten diuretic. AB - Chlorthalidone's safety and efficacy in the management of hypertension has been demonstrated in landmark trials. Despite understanding the effects of thiazides on urinary sodium excretion and intravascular volume, the exact mechanism of their antihypertensive effects is not clearly understood. Common compensatory mechanisms for decreases in circulating plasma volume include increased adrenergic tone and systemic vascular resistance, as well as increases in the renin-angiotensin-aldosterone system. Chlorthalidone has been shown to decrease platelet aggregation and vascular permeability and promote angiogenesis in vitro, which is thought to be, in part, the result of reductions in carbonic anhydrase dependent pathways, including catecholamine-mediated platelet aggregation and downregulation of VEGF-C gene expression. This article reviews the comparative clinical data between chlorthalidone and hydrochlorothiazide, the pharmacologic properties that might explain some of their differences regarding half-life and efficacy, and what is known about the effect of chlorthalidone on intermediate endpoints. PMID- 22314116 TI - Recent advancements in the treatment of resistant hypertension. AB - The 2008 scientific statement from the American Heart Association defined resistant hypertension as blood pressure remaining above goal (< 140/90 mm Hg for the general population and < 130/80 mm Hg for patients with diabetes or renal disease) despite the concurrent use of optimal doses of 3 antihypertensive agents of different classes, ideally including a diuretic. Since then, there has been increasing recognition and characterization of patients with resistant hypertension and development of treatment strategies to treat this high-risk population. The role of aldosterone in resistant hypertension has gained increasing recognition. In particular, there has been development of a strong body of evidence for the use of spironolactone as a highly effective antihypertensive agent. Furthermore, there is increasing evidence to link aldosterone with both resistant hypertension and obstructive sleep apnea, with preliminary studies suggesting that aldosterone antagonists may potentially be effective in treating both conditions. Finally, recent work has directed increased attention toward novel invasive strategies for the treatment of resistant hypertension, specifically baroreflex activation therapy with carotid stimulation and percutaneous renal artery denervation. Initial randomized controlled trials have shown that both of these methods may be used to safely lower blood pressure, thereby providing exciting and promising new tools in the armamentarium of options to treat resistant hypertension. PMID- 22314117 TI - Evaluation and pharmacologic approach to patients with resistant hypertension. AB - Patients are diagnosed as having resistant hypertension when they have blood pressure readings that remain above goal despite the concomitant use of 3 optimally dosed antihypertensive agents from different classes, with 1 of the agents being a diuretic. Prior to diagnosing a patient as having resistant hypertension, it is important to document adherence and exclude white-coat hypertension, inaccurate measurement of blood pressure, and secondary causes of hypertension (eg, aldosterone excess). After determining resistance, optimization of the medication regimen is essential. Combination strategies, which might include dual renin-angiotensin-aldosterone blockade with spironolactone as 1 agent, have been proven successful. This article focuses on the safety and efficacy of spironolactone when added to an optimized 3-drug regimen. Additionally, the use of spironolactone in chronic kidney disease and obstructive sleep apnea complicated by resistant hypertension is discussed. These 2 clinical entities are frequently accompanied by resistant hypertension and are indications for the use of spironolactone as well. PMID- 22314118 TI - A systematic review of duloxetine for osteoarthritic pain: what is the number needed to treat, number needed to harm, and likelihood to be helped or harmed? AB - OBJECTIVE: To describe the efficacy, safety, and tolerability of duloxetine for the treatment of osteoarthritic pain. DATA SOURCES: Systematic review of all published double-blind randomized controlled trials of duloxetine for osteoarthritic pain, supplemented by information in clinical trial registries, product labeling, and regulatory documents. STUDY SELECTION: All available reports of studies were identified. DATA EXTRACTION: Descriptions of the principal results and calculation of number needed to treat (NNT) for pain relief and other efficacy outcomes and number needed to harm (NNH) for relevant dichotomous adverse outcomes were extracted. Likelihood to be helped or harmed (LHH) was subsequently calculated. DATA SYNTHESIS: US Food and Drug Administration approval for duloxetine for chronic pain associated with osteoarthritis (OA) was based on 2 randomized, double-blind, placebo-controlled clinical trials of 13 weeks' duration testing duloxetine 60 to 120 mg/d versus placebo. When study results were pooled, the proportion of patients experiencing clinically meaningful outcomes at study endpoint, such as a >= 30% or >= 50% reduction in pain scores, improvement in physical functioning, or subjective improvement, ranged from 42% to 67% for duloxetine, compared with 26% to 50% for placebo, depending on the specific measure; the NNT for these measures for duloxetine versus placebo was 7. The most commonly observed adverse reactions in duloxetine-treated patients were nausea (8.4% vs 2.0% for duloxetine and placebo, respectively), fatigue (6.7% vs 0.8%, respectively), and constipation (6.3% vs 0.8%, respectively), yielding NNH values of 16, 17, and 19, respectively. The LHH was consistently > 1. CONCLUSIONS: Duloxetine appears efficacious and tolerable for the treatment of chronic pain associated with OA. The NNT and NNH can be used to quantify efficacy and tolerability outcomes and help place duloxetine into clinical perspective. Likelihood to be helped or harmed can illustrate to the clinician and patient the trade-offs between obtaining potential benefits versus harms. Head-to-head comparisons of duloxetine with other interventions for OA, as well as controlled trials of duloxetine in combination with other therapies, would be desirable. PMID- 22314119 TI - Hypoactive sexual desire disorder in premenopausal women: case studies. AB - Hypoactive sexual desire disorder (HSDD) is the most common female sexual dysfunction (FSD) and is thus frequently encountered in the primary care provider and OB/GYN practices. Causes of low sexual desire may be hormonal, neurologic, vascular, psychologic, or a result of illness/surgery or medications. The condition is often left untreated because both women and clinicians feel embarrassed to bring up the topic and believe that there is no available treatment. The use of short, validated questionnaires, such as the Decreased Sexual Desire Screener, to be completed in the waiting room, can open up discussion between provider and patient. In addition, 2 other algorithms are designed for clinicians who are not specifically trained in FSD and can help in diagnosing and managing a broad range of conditions related to FSD. Treatment for low desire consists primarily of patient education and counseling, as well as treatment of underlying comorbid conditions, such as diabetes, obesity, or cancer. While testosterone products are approved in Europe for use in surgically postmenopausal women with HSDD, in the United States, no pharmacologic treatments are approved for the treatment of HSDD or any FSD. Testosterone products are being used off-label, but questions remain about their efficacy and safety in pre and postmenopausal women. This article gives an overview of HSDD in clinical practice and provides 3 case descriptions to illustrate the treatment of low sexual desire in women with diverse histories. PMID- 22314120 TI - Contemporary management of overactive bladder. AB - Overactive bladder is a prevalent condition with bothersome symptoms that greatly impact health-related quality of life. Despite a multitude of treatment options, many patients go untreated or undertreated. This article addresses the contemporary management of overactive bladder, including behavioral and lifestyle modifications, pelvic floor muscle therapy, biofeedback, drug therapy, neuromodulation, and botulinum toxin. We highlight the new drugs and therapies that have been brought into clinical use over the past few years, and discuss important clinical implications of therapy as well as promising new agents that are currently in advanced stages of development. PMID- 22314121 TI - The pharmacokinetic parameters of a single dose of a novel nano-formulated, lower dose oral diclofenac. AB - INTRODUCTION: There is a clinical need for new nonsteroidal anti-inflammatory drugs (NSAIDs) and/or new formulations that, at minimum, retain the established efficacy of standard NSAIDs while minimizing their associated adverse events. This phase 1 clinical trial characterizes the pharmacokinetic (PK) profile of an investigational, proprietary, nano-formulated, lower-dose oral diclofenac (nano formulated diclofenac) compared with oral diclofenac in healthy subjects. METHODS: A single-center, single-dose, randomized, open-label, 5-period, 5 treatment, 10-sequence crossover study was completed in 30 healthy subjects. Subjects received either nano-formulated diclofenac 18 mg or 35 mg or diclofenac 50 mg in fed and fasting states. The maximum measured plasma concentration (Cmax), time to maximum measured concentration (Tmax), terminal elimination half life (T1/2), and area under the concentration time curve (AUC), along with safety and tolerability, were assessed. RESULTS: Mean (+/- standard deviation) Tmax for nano-formulated diclofenac 18 (0.62 +/- 0.35 h) and 35 mg (0.59 +/- 0.20 h) demonstrated faster absorption than diclofenac 50 mg (0.80 +/- 0.50 h). The T1/2 was similar between nano-formulated diclofenac 35 mg and diclofenac 50 mg (1.85 +/- 0.45 h vs 1.92 +/- 0.38 h, respectively). The Cmax for nano-formulated diclofenac 35 mg and diclofenac 50 mg was comparable in fasted subjects (1347 +/- 764 ng/mL vs 1316 +/- 577 ng/mL, respectively), but lower in fed subjects (524 +/ 222 ng/mL vs 951 +/- 391 ng/mL, respectively). As anticipated, there was a 19% reduction in drug exposure (AUC0(-infinity)) when subjects received nano formulated diclofenac 35 mg compared with diclofenac 50 mg under fasting conditions (1225 +/- 322 h*ng/mL vs 1511 +/- 389 h*ng/mL, respectively). Safety and tolerability were comparable between nano-formulated diclofenac and diclofenac. CONCLUSION: The novel nano-formulated, lower-dose diclofenac demonstrated lower systemic exposure, comparable Cmax, and faster absorption compared with diclofenac. In light of the advisory issued by worldwide regulatory agencies regarding use of lowest effective doses, these data may permit use of lower NSAID doses that improve safety and tolerability while, at minimum, relieving pain similar to standard formulations. PMID- 22314122 TI - Hypoglycemia, treatment discontinuation, and costs in patients with type 2 diabetes mellitus on oral antidiabetic drugs. AB - OBJECTIVE: To investigate the rate and impact of hypoglycemic events among patients with type 2 diabetes mellitus (T2DM) receiving different classes of oral antidiabetic drugs (OADs). RESEARCH DESIGN AND METHODS: Adult patients with T2DM were extracted from the Ingenix IMPACT claims database. The mean number of health care visits due to hypoglycemic events per patient-year was estimated. Multivariate regression models were used to: 1) assess the risk factors for experiencing a hypoglycemic event; 2) assess the effect of experiencing hypoglycemic events on antidiabetic treatment discontinuation; and 3) compare 12 month post-index date costs between patients with and without hypoglycemic events. RESULTS: 212 061 patients with T2DM were included in the analysis. The estimated frequency of hypoglycemia-related health care visits was 0.054 per patient-year. Insulin use was associated with increased risk of developing hypoglycemia, followed by use of sulfonylureas and other OADs (eg, meglitinide and alpha-glucosidase inhibitors). The impacts of thiazolidinediones, metformin, and dipeptidyl peptidase-4 on hypoglycemia risk were relatively small. Having a hypoglycemic event was associated with significantly increased risk of antidiabetic treatment discontinuation. Patients with hypoglycemia showed significantly higher annual all-cause and diabetes-related health care costs than patients without hypoglycemia (adjusted Delta = +$5024 and +$3747, respectively; both P < 0.0001). CONCLUSION: Different OAD classes were associated with different levels of risk for hypoglycemic events. Hypoglycemia was associated with a higher risk of antidiabetic treatment discontinuation and significantly increased health care costs. PMID- 22314123 TI - Clinical management of elderly patients with type 2 diabetes mellitus. AB - With an increase in life expectancy of the general population comes an increase in the number of elderly patients with type 2 diabetes mellitus (T2DM). Although the pharmacologic treatment options for elderly patients with T2DM are the same as for younger adults, management of this growing group poses unique challenges. Changes in renal and hepatic function and an increased prevalence of multiple comorbidities mandate an individually tailored treatment strategy that balances treatment benefits with the patient's functional status and risk for hypoglycemia and polypharmacy. This approach is hampered by the relative paucity of data regarding the pharmacotherapy of T2DM in older adults, necessitating clinical guidance based on data extrapolated from a younger population. Most current guidelines are disease-focused and do not include specific instructions on how to prioritize the treatment of hyperglycemia relative to that of other comorbidities and the functional status of patients. This article reviews the epidemiology, pathophysiology, comorbidities, pharmacokinetic considerations, treatment goals, guidelines, and treatment options for the elderly population, and highlights the current knowledge gaps complicating the management of T2DM in this population. PMID- 22314124 TI - Life with hereditary angioedema: then and now. AB - Originally identified in 1882, hereditary angioedema (HAE) is a debilitating and potentially fatal disorder. Although a number of therapies have been identified, many are relatively ineffective or are associated with significant side effect concerns that limit their efficacy. Fortunately, the 2008 approval of plasma derived C1 esterase inhibitor concentrate for disease prophylaxis provides clinicians with a novel and effective treatment unencumbered with severe side effect concerns for those with this debilitating disorder. However, despite advances in modern medicine, HAE remains a condition marked by a myriad of symptoms that mimic a range of other disorders, from allergic angioedema to acute abdomen, and accurate diagnosis remains a concern. Using articles from the medical literature from the late nineteenth and early twentieth centuries documenting families with HAE, we will review its history and pathophysiology as well as describe current trends in its diagnosis and treatment. Additionally, we will emphasize the humanistic impact of the disorder by describing the real-life experiences of a contemporary family who has documented their experience with HAE across 7 generations. PMID- 22314125 TI - The nature, assessment, and treatment of obsessive-compulsive disorder. AB - Obsessive-compulsive disorder (OCD) is an anxiety disorder that affects between 1% to 2% of individuals and causes considerable impairment and disability. Although > 50% of individuals experience symptom onset in childhood, symptoms can continue to develop throughout adulthood. Accurate and timely assessment of clinical presentation is critical to limit impairment and improve prognosis. Presently, there are 2 empirically supported treatments available for OCD in children and adults, namely cognitive-behavioral therapy and pharmacotherapy with serotonin reuptake inhibitors. This article provides an introduction to the phenomenology, etiology, and clinical course of OCD. Assessment practices used to evaluate symptom severity are described, and evidence-based treatment options are reviewed, with appropriate distinctions drawn between children and adults. Finally, recommendations for assessment and treatment practices for OCD are explicated. PMID- 22314126 TI - Importance of pharmacokinetic profile and timing of coadministration of short- and long-acting formulations of methylphenidate on patterns of subjective responses and abuse potential. AB - OBJECTIVE: Subjective responses (ie, liking, disliking) to stimulants are thought to be proxies for abuse potential. Greater subjective responses have been documented in formulations that are more rapidly absorbed. However, repeat dosing has not been examined. METHODS: Subjective responses on the Drug Rating Questionnaire were compared in 26 healthy adults after administration of short- (immediate-release [IR] methylphenidate [MPH]) and long- (osmotically controlled release oral delivery system [OROS] MPH) acting stimulant formulations. The second dose was administered 4 hours after initial dosing. All subjects received all 5 conditions (ie, placebo to placebo; IR-MPH to IR-MPH; IR-MPH to OROS-MPH; OROS-MPH to IR-MPH; or OROS-MPH to OROS-MPH) in a double-blind, counter-balanced design on 5 separate days. RESULTS: Plasma levels and subjective patterns of detection were higher when an IR formulation was administered during the ascending phase of a first-administered long-acting dose (OROS). CONCLUSION: These results emphasize the critical role that formulation type (IR vs OROS) and timing of administration (ascending vs descending phase) play when short- and long-acting formulations are coadministered. Such knowledge provides important information for clinicians about the safety and tolerability of the timing of repeat dosing of various permutations of coadministration of MPH formulations. PMID- 22314128 TI - Germline DNA copy number variation in familial and early-onset breast cancer. AB - INTRODUCTION: Genetic factors predisposing individuals to cancer remain elusive in the majority of patients with a familial or clinical history suggestive of hereditary breast cancer. Germline DNA copy number variation (CNV) has recently been implicated in predisposition to cancers such as neuroblastomas as well as prostate and colorectal cancer. We evaluated the role of germline CNVs in breast cancer susceptibility, in particular those with low population frequencies (rare CNVs), which are more likely to cause disease." METHODS: Using whole-genome comparative genomic hybridization on microarrays, we screened a cohort of women fulfilling criteria for hereditary breast cancer who did not carry BRCA1/BRCA2 mutations. RESULTS: The median numbers of total and rare CNVs per genome were not different between controls and patients. A total of 26 rare germline CNVs were identified in 68 cancer patients, however, a proportion that was significantly different (P = 0.0311) from the control group (23 rare CNVs in 100 individuals). Several of the genes affected by CNV in patients and controls had already been implicated in cancer. CONCLUSIONS: This study is the first to explore the contribution of germline CNVs to BRCA1/2-negative familial and early-onset breast cancer. The data suggest that rare CNVs may contribute to cancer predisposition in this small cohort of patients, and this trend needs to be confirmed in larger population samples. PMID- 22314129 TI - Predictive capacity of four comorbidity indices estimating perioperative mortality after radical cystectomy for urothelial carcinoma of the bladder. AB - What's known on the subject? and What does the study add? The degree of comorbidity significantly affects the course of patients with bladder cancer undergoing radical cystectomy (RC). To our knowledge this is the first study comparing four different comorbidity indices in patients undergoing RC for urothelial carcinoma to assess the best clinical predictors for 90-day perioperative mortality. We concluded that the ASA score should be the method of choice, as it showed a predictive ability superior to that of ECOG and CCI, and is much easier to generate than the ACE-27. OBJECTIVE: To evaluate which of the following among the Adult Comorbidity Evaluation-27 (ACE-27), the Charlson Comorbidity Index (CCI), the Eastern Cooperative Oncology Group performance status (ECOG) and the American Society of Anesthesiologists (ASA) comorbidity scores correlate best with perioperative mortality after radical cystectomy (RC) for urothelial carcinoma (UC) of the bladder. PATIENTS AND METHODS: A study was carried out on 555 unselected consecutive patients without neoadjuvant chemotherapy who underwent RC for UC of the bladder from 2000 to 2010 at one of two institutions. Patients' medical records were reviewed retrospectively. We established a defined binary linear progression model based on clinical variables to predict perioperative mortality <90 days after RC (90PM). To this model we added, individually, the comorbidity indices ACE-27, CCI, ECOG, and ASA to assess their predictive capacity regarding 90PM. RESULTS: The overall 90PM was 7.9%. Age (P = 0.01) and clinical distant metastatic tumour stage (P = 0.002) were independent predictors for 90PM in the multivariate analysis. Each of the four investigated comorbidity indices was able to significantly increase the predictive capacity of the basic model: ECOG +13.5%, (odds ratio [OR]: 1.61, P = 0.036; area under the curve [AUC] 74.7), ASA Score +28.3% (OR: 2.19, P = 0.004; AUC 76.1), Charlson Index +12.3% (OR: 1.31, P = 0.047; AUC 73.8) and ACE-27 + 29.8% (OR: 1.72, P = 0.004; AUC 76.1). CONCLUSIONS: ASA and ACE-27 show a nearly identical clinical predictive value for perioperative mortality. Both scores could be considered for clinical practice. With regard to ease of generation and availability, the ASA score can be regarded as the best instrument. PMID- 22314130 TI - Development of a clinical trial to determine whether watchful waiting is an acceptable alternative to surgical repair for patients with oligosymptomatic incisional hernia: study protocol for a randomized controlled trial. AB - BACKGROUND: Incisional hernia is a frequent complication in abdominal surgery. This article describes the development of a prospective randomized clinical trial designed to determine whether watchful waiting is an acceptable alternative to surgical repair for patients with oligosymptomatic incisional hernia. METHODS/DESIGN: This clinical multicenter trial has been designed to compare watchful waiting and surgical repair for patients with oligosymptomatic incisional hernia. Participants are randomized to watchful waiting or surgery and followed up for two years. The primary efficacy endpoint is pain/discomfort during normal activities as a result of the hernia or hernia repair two years after enrolment, as measured by the hernia-specific Surgical Pain Scales (SPS). The target sample size of six hundred thirty-six patients was calculated to detect non-inferiority of the experimental intervention (watchful waiting) in the primary endpoint. Sixteen surgical centers will take part in the study and have submitted their declaration of commitment giving the estimated number of participating patients per year. A three-person data safety monitoring board will meet annually to monitor and supervise the trial. DISCUSSION: To date, we could find no published data on the natural course of incisional hernias. To our knowledge, watchful waiting has never been compared to standard surgical repair as a treatment option for incisional hernias. A trial to compare the outcome of the two approaches in patients with oligosymptomatic incisional hernias is urgently needed to provide data that can facilitate the choice between treatment options. If watchful waiting was equal to surgical repair, the high costs of surgical repair could be saved. The design for such a trial is described here. This multicenter trial will be funded by the German Research Foundation (DFG). The ethics committee of the Charite has approved the study protocol. Approval has been obtained from ten study sites at time of this submission. The electronic Case Report Forms have been created. The first patient was to be randomized November 14th, 2011. An initiation meeting took place in Berlin January 9th, 2012. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01349400. PMID- 22314131 TI - Attitudes of mental health staff to protected therapeutic time in adult psychiatric wards. AB - Therapeutic time is a relatively new, ward-based intervention whereby psychiatric nurses spend regular, uninterrupted periods of time with patients during which they do not attend to other matters. A questionnaire survey of nursing and medical staff was conducted to assess attitudes to the approach. The majority of staff viewed the approach as being important for promoting patient recovery, reducing risk, improving nurse-patient relationships and enhancing patient satisfaction with care received. Interference with medical activities, lack of staffing resources and variable patient uptake were highlighted as potential problems. More research is required to establish the benefits, drawbacks and nature of therapeutic time. Given the current support for the approach and previous research emphasizing the extent to which patients value protected time to speak to nurses, investment of resources in further exploration and implementation of this approach may lead to significant clinical returns. PMID- 22314132 TI - Ionizing radiation-induced mutant frequencies increase transiently in male germ cells of older mice. AB - Spontaneous mutant frequency in the male germline increases with age, thereby increasing the risk of siring offspring with genetic disorders. In the present study we investigated the effect of age on ionizing radiation-induced male germline mutagenesis. lacI transgenic mice were treated with ionizing radiation at 4-, 15- and 26-month-old, and mutant frequencies were determined for pachytene spermatocytes and round spermatids at 15 days or 49 days after ionizing radiation treatment. Cells collected 15 days after treatment were derivatives of irradiated differentiating spermatogenic cells while cells collected 49 days later were derivatives of spermatogonial stem cells. The results showed that (1) spontaneous mutant frequency increased in spermatogenic cells recovered from nonirradiated old mice (26-months-old), particularly in the round spermatids; (2) mutant frequencies were significantly increased in round spermatids obtained from middle aged mice (15-months-old) and old age mice (26-months-old) at 15 and 49 days after irradiation compared to the sham-treated old mice; and (3) pachytene spermatocytes obtained from 15- or 26-month-old mice displayed a significantly increased mutant frequency at 15 days post irradiation. This study indicates that age modulates the mutagenic response to ionizing radiation in the male germline. PMID- 22314133 TI - Immunization with apoptotic pseudovirus transduced cells induces both cellular and humoral responses: a proof of concept study in macaques. AB - Dendritic cells are able to present viral antigens to T-cells after uptake of apoptotic bodies derived from virus-infected cells. Immunization with virus infected apoptotic cells was previously shown to induce HIV-specific immune responses in mice. Here we evaluate the safety and immunogenicity of immunization with activated apoptotic cells in non-human primates using autologous T-cells infected with replication defective VSV pseudotyped SIV(mac239)Deltaenv. Animals were immunized with gamma-irradiated activated T-cells carrying the VSVenvSIV(mac239)Deltaenv pseudovirus. SIV Gag-specific cellular immune responses were induced as early as two weeks after the first immunization eliciting a biased IFN-gamma and IL-2 response. In addition, induction of SIV Gag-specific antibody responses and high titer neutralizing activity against the SIV pseudovirus harboring a VSV-env were detected after two immunizations. The vaccinated group and a control group of Chinese rhesus macaques were intravenously challenged with pathogenic SIV(mac251.) All animals became infected, but SIV-replication was effectively suppressed (below 100 copies/ml) in several animals in both groups. However the group immunized with apoptotic cells revealed better preservation of the gut CD4(+) T-cell compartment. Viral control was inversely correlated with an early (4 weeks) but transient increase in the percentage of Ki67(+)CD4(+) peripheral blood T-cells (Spearman -0.73). We here show that immunizations with activated apoptotic lymphocytes expressing transduced SIV genes result in induction of both cellular and humoral immune responses. This study provides evidence for an immunological principle demonstrating that certain apoptotic cells can be considered as carriers of antigens directing immune responses in macaques. PMID- 22314134 TI - A TLR4 agonist synergizes with dendritic cell-directed lentiviral vectors for inducing antigen-specific immune responses. AB - TLR4 agonists can be used as adjuvants to trigger innate immune responses of antigen-presenting cells (APCs) such as dendritic cells (DCs) to enhance vaccine specific immunity. Adjuvant effects of TLR4 agonists are mediated by downstream signaling controlled by both MyD88 and TRIF adapter proteins. In this study, we investigated the adjuvanting capacity of glucopyranosyl lipid A (GLA), a chemically synthesized TLR4 agonist, to boost antigen-specific immunity elicited by DC-directed lentiviral vectors (DC-LV). We found that stimulation by this agonist in vitro can activate DCs in a TLR4-dependent manner. The agonist can significantly boost DC-LV-induced humoral and cellular immune responses, resulting in better antitumor reactions in response to tumor challenges. We observed that the adjuvant-mediated enhancement of cytotoxic CD8(+) T cell responses is CD4(+) T cell-dependent and determined that in vitro the agonist stimulation involves the participation of both MyD88 and TRIF pathways to activate DCs. In vivo immunization study however revealed that adjuvant effects depend more on the MyD88 signaling as TRIF(-/-) mice but not MyD88(-/-) mice were able to maintain the enhanced CD8(+) T cell responses upon DC-LV immunization. Thus, our study supports the use of this TLR4 agonist as a potent adjuvant candidate for boosting DC-LV immunization. PMID- 22314135 TI - Recombinant gp90 protein expressed in Pichia pastoris induces a protective immune response against reticuloendotheliosis virus in chickens. AB - Reticuloendotheliosis virus (REV) causes an oncogenic, immunosuppressive and runting syndrome in multiple avian hosts worldwide. In this study, the gp90 protein of REV was secretory expressed in Pichia pastoris with high production level and good antigenicity. To fully utilize the expression potential of the P. pastoris expression system, a panel of Pichia clones carrying increasing copies of the gp90 expression cassette was created using an in vitro multimerization approach and the effects of gene dosage on gp90 expression were investigated. Results demonstrated that an increase in gp90 copy number can significantly improve the yields of gp90 protein. Following expression and scale-up, the gp90 protein production level could reach up to 400mg/L, and the protein could be detected by gp90-specific monoclonal antibody. Investigations of its vaccine efficacy demonstrated that the recombinant gp90 protein was able to induce sustained high levels of antibodies against REV as being detected by ELISA and virus neutralizing test. Furthermore, immunization of chickens with the recombinant gp90 vaccine fully protected the animals from viremia after REV infection. Overall, the yeast-expressed gp90 protein retains good immunogenicity and could be used as a potential subunit vaccine candidate for REV prevention. PMID- 22314136 TI - Immunological impact of an additional early measles vaccine in Gambian children: responses to a boost at 3 years. AB - BACKGROUND: Measles vaccine in early infancy followed by a dose at 9 months of age protects against measles and enhances child survival through non-specific effects. Little is known of immune responses in the short or long term after booster doses. METHODS: Infants were randomized to receive measles vaccine at 9 months of age (group 1) or 4 and 9 months of age (group 2). Both groups received a boost at 36 months of age. T-cell effector and memory responses using IFN-gamma ELIspot and cytokine assays and antibody titres using a haemagglutination inhibition assay were compared at various times. RESULTS: Vaccination at 4 months of age elicited antibody and CD4 T-cell mediated immune responses .Two weeks after vaccination at 9 months of age group 2 had much higher antibody titres than group1 infants; cell-mediated effector responses were similar. At 36 months of age group 2 antibody titres exceeded protective levels but were 4-fold lower than group 1; effector and cytokine responses were similar. Re-vaccination resulted in similar rapid and high antibody titres in both groups (median 512); cellular immunity changed little. At 48 months of age group 2 antibody concentrations remained well above protective levels though 2-fold lower than group 1; T-cell memory was readily detectable and similar in both groups. CONCLUSIONS: An additional early measles vaccine given to children at 4 months of age induced a predominant CD4 T-cell response at 9 months and rapid development of high antibody concentrations after booster doses. However, antibody decayed faster in these children than in the group given primary vaccination at 9 months of age. Cellular responses after 9 months were generally insignificantly different. PMID- 22314137 TI - Construction of a cellulase hyper-expression system in Trichoderma reesei by promoter and enzyme engineering. AB - BACKGROUND: Trichoderma reesei is the preferred organism for producing industrial cellulases. However, a more efficient heterologous expression system for enzymes from different organism is needed to further improve its cellulase mixture. The strong cbh1 promoter of T. reesei is frequently used in heterologous expression, however, the carbon catabolite repressor CREI may reduce its strength by binding to the cbh1 promoter at several binding sites. Another crucial point to enhance the production of heterologous enzymes is the stability of recombinant mRNA and the prevention of protein degradation within the endoplasmic reticulum, especially for the bacteria originated enzymes.In this study, the CREI binding sites within the cbh1 promoter were replaced with the binding sites of transcription activator ACEII and the HAP2/3/5 complex to improve the promoter efficiency. To further improve heterologous expression efficiency of bacterial genes within T. reesei, a flexible polyglycine linker and a rigid alpha-helix linker were tested in the construction of fusion genes between cbh1 from T. reesei and e1, encoding an endoglucanase from Acidothermus cellulolyticus. RESULTS: The modified promoter resulted in an increased expression level of the green fluorescent protein reporter by 5.5-fold in inducing culture medium and 7.4 fold in repressing culture medium. The fusion genes of cbh1 and e1 were successfully expressed in T. reesei under the control of promoter pcbh1m2. The higher enzyme activities and thermostability of the fusion protein with rigid linker indicated that the rigid linker might be more suitable for the heterologous expression system in T. reesei. Compared to the parent strain RC30 8, the FPase and CMCase activities of the secreted enzyme mixture from the corresponding transformant R1 with the rigid linker increased by 39% and 30% at 60 degrees C, respectively, and the reduced sugar concentration in the hydrolysate of pretreated corn stover (PCS) was dramatically increased by 40% at 55 degrees C and 169% at 60 degrees C when its enzyme mixture was used in the hydrolysis. CONCLUSIONS: This study shows that optimizations of the promoter and linker for hybrid genes can dramatically improve the efficiency of heterologous expression of cellulase genes in T. reesei. PMID- 22314138 TI - Identification and functional characterization of the novel human ether-a-go-go related gene (hERG) R744P mutant associated with hereditary long QT syndrome 2. AB - Mutations of the cyclic nucleotide binding domain (CNBD) may disrupt human ether a-go-go-related gene (hERG) K(+) channel function and lead to hereditary long QT syndrome (LQTS). We identified a novel missense mutation located in close proximity to the CNBD, hERG R744P, in a patient presenting with recurrent syncope and aborted cardiac death triggered by sudden auditory stimuli. Functional properties of wild type (WT) and mutant hERG R744P subunits were studied in Xenopus laevis oocytes using two-electrode voltage clamp electrophysiology and Western blot analysis. HERG R744P channels exhibited reduced activating currents compared to hERG WT (1.48+/-0.26 versus 3.40+/-0.29MUA; n=40). These findings were confirmed by tail current analysis (hERG R744P, 0.53+/-0.07MUA; hERG WT, 0.97+/-0.06MUA; n=40). Cell surface trafficking of hERG R744P protein subunits was not impaired. To simulate the autosomal-dominant inheritance associated with LQTS, WT and R744P subunits were co-expressed in equimolar ratio. Mean activating and tail currents were reduced by 32% and 25% compared to hERG WT (n=40), indicating that R744P protein did not exert dominant-negative effects on WT channels. The half-maximal activation voltage was not significantly affected by the R744P mutation. This study highlights the significance of in vitro testing to provide mechanistic evidence for pathogenicity of mutations identified in LQTS. The functional defect associated with hERG R744P serves as molecular basis for LQTS in the index patient. PMID- 22314139 TI - Focal defect of mastoid bone shell in the region of the transverse-sigmoid junction: a new cause of pulsatile tinnitus. AB - OBJECTIVE: Pulsatile tinnitus usually originates from vascular structures, causing an arterial or venous bruit. We report a new cause of pulsatile tinnitus: a focal defect of the mastoid bone shell in the region of the transverse-sigmoid junction, with a normal transverse-sigmoid sinus. PARTICIPANTS AND INTERVENTION: Three patients complained of unilateral, pulsatile tinnitus present for many years. They were identified as having a focal defect of the mastoid bone shell in the region of the transverse-sigmoid junction. The patients underwent transmastoid reconstruction of the mastoid bone shell overlying the transverse sigmoid sinus. RESULTS: All three patients reported immediate resolution of their symptoms, and were asymptomatic at final follow up. CONCLUSION: A focal defect of the mastoid bone shell overlying the transverse-sigmoid sinus, with no abnormality of the sinus itself, may be a new cause of pulsatile tinnitus. Surgical reconstruction of the mastoid bone shell overlying the transverse sigmoid sinus can provide lasting symptom relief for patients with pulsatile tinnitus and computed tomographic evidence of the defect. PMID- 22314140 TI - Radiation-induced heart disease. AB - Radiation-induced heart disease (RIHD) is becoming an increasing concern for patients and clinicians alike as the use of radiation therapy for the treatment of certain malignancies increases, and patient mortality secondary to neoplasms of the thorax, in particular Hodgkin's lymphoma and breast cancer, decreases. The spectrum of pathology affecting the heart spans from acute to chronic and can affect almost all facets of the heart, including but not restricted to the pericardial sac, coronary arteries, myocardium, and heart valves. Significant research has been conducted over the past 40 years to further understand the toxic effects of radiation therapy and those protective methods that could curtail these adverse reactions. This article will focus on RIHD, the pathophysiological mechanisms for RIHD, the clinical presentations, and current and future directions for attempting to reduce the incidence of this condition. PMID- 22314141 TI - Advanced glycation end products and diabetic cardiovascular disease. AB - Advanced glycation end products (AGEs) are formed by a nonenzymatic reaction of sugar moieties (eg, glucose, fructose, glycolytic adducts) with the free amino groups on amino acid residues of proteins. A growing body of data demonstrate that AGEs are intimately involved in the pathophysiology of cardiovascular disease by stimulating inflammation, contributing to atheroma formation, and modulating vascular stiffness. The role of AGEs as potential biomarkers for disease presence and prognosis in patients with diabetes mellitus remains an active area of study. Epidemiologic and angiographic studies suggest that AGE levels may be related to the presence and extent of atherosclerosis, and may predict future outcomes in select populations. The present review summarizes the relevant evidence supporting the role of advanced glycation in promoting atherosclerosis and the epidemiologic studies demonstrating an association between AGEs and diabetic cardiovascular disease. PMID- 22314142 TI - Growth hormone and the cardiovascular system. AB - Growth hormone (GH) exerts its effects through insulin-like growth factor-1, and although ubiquitous in human tissues, it has a significant role in cardiovascular function. In recent years, there has been a great deal of interest in GH as an etiologic factor in many cardiovascular disease states. Acromegaly, a state of endogenous GH excess, results in myocardial hypertrophy and decreased cardiac performance with increased cardiovascular mortality. Additional insight into the role of excess GH on the cardiovascular system has been gained from data collected in athletes doping with GH. Likewise, GH deficiency is associated with increased mortality, possibly from the associated increase in atherosclerosis, lipid abnormalities, and endothelial dysfunction. However, further research is required to clarify the benefit of GH treatment in both deficient states and in heart failure patients. PMID- 22314143 TI - Cardiovascular disease and risk factors in law enforcement personnel: a comprehensive review. AB - Law enforcement is a high-stress occupation that is prone to increasing the prevalence and incidence of cardiovascular disease. Epidemiological studies suggest that police officers and related public safety personnel have an increased risk of cardiovascular morbidity and mortality. Currently employed police personnel have a high prevalence of traditional risk factors, including hypertension, hyperlipidemia, metabolic syndrome, cigarette smoking, and a sedentary lifestyle. Obesity may be more common in police officers compared with civilians, whereas diabetes is present less frequently. Law enforcement personnel are also exposed to occupation-specific risk factors that include sudden physical exertion, acute and chronic psychological stress, shift work, and noise. Workplace programs to promote the health and fitness of police officers are commonly lacking, but can be an effective means for reducing cardiovascular risk. Physicians should be familiar with the essential job tasks required for police officers to determine whether the individual is fit for duty. Governmental agencies have established strategic goals to reduce cardiovascular complications and improve the health and wellness of public safety personnel. PMID- 22314144 TI - Revascularization in renal artery stenosis. AB - The predominant cause of renal artery stenosis (RAS) is atherosclerosis. Clinical manifestations of atherosclerotic RAS are both direct (hypertension and kidney dysfunction) and indirect (increased cardiovascular events and mortality). However, in many cases, atherosclerotic RAS seems to be an incidental finding with no discernable effects. Antihypertensive medications such as renin angiotensin-aldosterone system inhibitors, along with statins and aspirin, have significantly improved the medical treatment of atherosclerotic RAS. However, revascularization is still advocated in a variety of clinical settings such as the preservation of renal function, recurrent episodes of "flash" pulmonary edema, and in patients with refractory hypertension. Current management guidelines indicate "resistant hypertension" as an indication for renal artery revascularization. A large number of observational studies support revascularization for both control of high blood pressure and/or preservation of renal function. Unfortunately, the favorable effects of revascularization on these end points seen in the observational studies were not reproduced in randomized controlled trials compared to medical therapy alone. The ability for revascularization to improve control of congestive heart failure or to prevent hard cardiovascular end points (eg, myocardial infarction or stroke) has not been tested in the randomized clinical trials published to date. Hence, the efficacy of intervention remains controversial, which poses a dilemma, especially given the large number of elderly patients with resistant systolic hypertension. PMID- 22314145 TI - Carcinoid heart disease. AB - Carcinoid tumors are rare, indolent neuroendocrine tumors that are often associated with a syndrome characterized by episodic flushing, secretory diarrhea, bronchospasm, and hypotension-the carcinoid syndrome. Cardiac involvement occurs in one-half to two-thirds of patients with carcinoid syndrome and is associated with a worse clinical outcome. Carcinoid heart disease is characterized by endocardial plaque-like deposits found predominantly on right sided heart valves, leading to the combination of valvular stenosis and regurgitation. Left-sided cardiac involvement can also occur in <10% of patients. Somatostatin analogs form the therapeutic cornerstone in the medical management of these patients. Cytotoxic chemotherapy has had only limited success in the treatment of metastatic carcinoid tumors. Hepatic resection or palliative cytoreduction may be of benefit in patients with limited hepatic disease. Hepatic artery embolization is usually applied if a patient is not eligible for surgical debulking. The development and progression of carcinoid heart disease are associated with an unfavorable outcome. In those patients having severe cardiac involvement and well-controlled systemic disease, valve replacement surgery has been found to be an effective treatment that can both relieve intractable symptoms and contribute to improved clinical outcomes. PMID- 22314146 TI - Laughter-induced syncope. AB - Reported cases of syncope caused directly by laughter are rare. The common scenario described in a few reports involved episodes of fortuitous laughter, sometimes followed by a short prodrome of lightheadedness, facial flushing, and dizziness, followed by an episode of definite syncope. There were no seizure-like movements, automatisms, or bladder or bowel incontinence. After the syncopal episodes that were seconds in length, the patients regained consciousness, and at that point were fully oriented. These episodes could recur in a similar situation with such laughter. Many of these patients subsequently underwent full syncope workups, without elucidating a primary cardiac or neurologic cause. In this review of laughter-induced syncope, we describe a patient of ours who fit these descriptions. This phenomenon is likely a subtype of benign Valsalva-related syncope, with autonomic reflex arcs coming into play that ultimately result in global cerebral hypoperfusion. Besides the Valsalva produced by a great fit of laughter, laughter itself has its own neuroendocrine and vasculature effects that may play a role. PMID- 22314147 TI - Changes in fat contents of US snack foods in response to mandatory trans fat labelling. AB - OBJECTIVE: Impact of mandatory trans fat labelling on US snack food introductions is examined. DESIGN: Using label information, lipid ingredients and fat profiles are compared pre- and post-labelling. SETTING: Key products in the US snack food industry contribute significant amounts of artificial trans fat. Industry efforts to reformulate products to lower trans fat may alter the overall fat profile, in particular saturates. SUBJECTS: Composition data for more than 5000 chip and cookie products introduced for sale between 2001 (pre-labelling) and 2009 (post labelling) were analysed. RESULTS: One-way ANOVA was used to test for significant changes in saturated fat content per serving and the ratio of saturated to total fat. The shares of chip and cookie introductions containing partially hydrogenated vegetable oil declined by 45 and 42 percentage points, respectively. In cookies, there was an increase of 0.49 (98 % CI 0.01, 0.98) g in the average saturated fat content per 30 g serving and an increase of 9 (98 % CI 3, 15) % in the average ratio of saturated to total fat. No statistically significant changes in fat content were observed in chips. CONCLUSIONS: This research suggests that, holding other factors constant, the policy has resulted in a decreased use of partially hydrogenated vegetable oil in chip products without a corresponding increase in saturated fat content, but led to significantly higher levels of saturated fat and ratio of saturated fat to total fat in cookie products. PMID- 22314148 TI - Effect of nanoparticle dimensionality on fluorescence resonance energy transfer in nanoparticle-dye conjugated systems. AB - Fluorescence resonance energy transfer (FRET) involving a semiconductor nanoparticle (NP) acting as a donor, attached to multiple acceptors, is becoming a common tool for sensing, biolabeling, and energy transfer applications. Such nanosystems, with dimensions that are in the range of FRET interactions, exhibit unique characteristics that are related to the shape and dimensionality of the particles and to the spatial distribution of the acceptors. Understanding the effect of these parameters is of high importance for describing the FRET process in such systems and for utilizing them for different applications. In order to demonstrate these dimensionality effects, the FRET between CdSe/CdS core/shell NPs with different geometries and dimensionalities and Atto 590 dye molecules acting as multiple acceptors covalently linked to the NP surface is examined. Steady-state emission and temporal decay measurements were performed on the NPs, ranging from spherical to rod-like shaped systems, as a function of acceptor concentration. Changes in the NP geometry, and consequently in the distributions of acceptors, lead to distinctively different FRET behaviors. The results are analyzed using a modified restricted geometries model, which captures the dimensionality of the acceptor distribution and allows extracting the concentration of dye molecules on the surface of the NP for both spherical and elongated NPs. The results obtained from the model are in good agreement with the experimental results. The approach may be useful for following the spatial dynamics of self-assembly and for a wide variety of sensing applications. PMID- 22314149 TI - [Clinicopathologic analysis of small-sized non-small cell lung cancer]. AB - We reviewed the data on 149 patients who underwent complete resection for small sized (<= 2 cm)peripheral non-small cell lung cancer at our institution between January 2002 and July 2010. Patients with small-sized lung cancer underwent a lobectomy in 121, segmentectomy in 13, and wedge resection in 15 cases. The overall and 5-year disease-free survivals were 89% and 82%, respectively. The 5 year disease-free survival of patients with tumors exceeding 1.5 cm was lower than that of patients with tumors 1.5 cm or smaller (p=0.01). The 5-year disease free survival for patients without pleulal invasion was 87%, whereas it was 45% for those with pleulal invasion (p=0.004). The 5-year disease-free survival according to the serum level of carcinoembrionic antigen( CEA) were 82% for the normal group and 70% for the high group( p=0.007). Although the results were not significantly different, patients with tumors with high maximum standardized uptake value (SUV) on FDG-PET/CT showed a trend toward a lower 5-year disease free survival rate( p=0.10). There were no recurrences in patients with ground glass opacity (GGO) or GGO-dominant lesion including those who underwent sublober resection. Multivariate analysis showed that tumor size and pleural invasion were independent prognostic factors. Indication of sublober resection for solid-type small-sized non-small cell lung cancer (NSCLC) should be carefully determined considering tumor size, pleural involvement, serum carcinoembryonic antigen( CEA) level, and maximum SUV. PMID- 22314150 TI - [Clinicopathological features of peripheral small-sized (2 cm or less in diameter) non-small cell lung cancer]. AB - Ninety-three patients with completely resected peripheral non-small cell lung cancer, clinically diagnosed 2 cm or less in diameter, were retrospectively reviewed. Their preoperative computed tomography (CT) and positron emission tomography (PET) findings, carcinoembryonic antigen (CEA) values, clinico pathological features and postoperative outcomes were analysed. Ground-glass opacity (GGO) ratio( soft tissue density area of the tumor/maximum area of the tumor in diameter) was measured. The overall survival rate at 3 years was 93.3% and the relapse-free survival rate at 3 years was 89.4% with a median follow-up period of 38.5 months. Patients with GGO ratio 0.25 or less had no lymph node (LN) involvement nor lymph vascular invasion. Only 2 of them (8%) had vascular invasion. Fisher's exact probability test revealed CEA >= 5 ng/ ml as risk factor for LN involvement( p=0.0400). Multiple logistic regression analysis showed that solid adenocarcinoma and squamous cell carcinoma recurred more frequently than adenocarcinoma with GGO (p=0.0619, odds ratio 4.969, 95%CI 0.9242~37.67). PMID- 22314151 TI - [Surgical outcome for small-sized non-small-cell lung cancer]. AB - We reviewed surgical outcome for small-sized non-small-cell lung cancer. From 2004 to 2007, 109 patients with complete resected non-small-cell lung cancer of 2 cm or less in diameter were examined retrospectively. Sixty-five were male and 44 were female. Ages ranged 41~87 (median 68) years.Overall 5-year survival rate(OS) was 89%, and 5-year disease free survival rate(DFS) was 82%.Ground-glass opacity( GGO) dominant group[ GGO ratio >= 50% in high resolution computed tomography(CT)] and lymph node (LN) negative group were showed favorable DFS significantly. Other parameters,such as histology, tumor diameter, serum carcinoembryonic antigen (CEA) level, pleural invasion,vascular permeation, operative procedure, were showed no significant difference about DFS. All GGO dominant group patients(n=23) had no LN involvement and survived in disease free. Cases with LN involvement [n=10 (9%)] were all in solid group(GGO<50%) and their tumor diameter were over 10 mm. Sublober resections were performed in 28 cases( segmentectomy in 12, wedge resection in 16). Among these cases, intentional limited resections were done in 13 patients with GGO dominant group (tumor diameter ranged 7 to 20 mm), and they had no local recurrence. Prognosis of small-sized GGO dominant lung cancer is very favorable, so limited resection will be appropriate. But solid lesions, especially over 10 mm in tumor diameter, have possibility of LN involvement, lobectomy should be considered. PMID- 22314152 TI - [Clinicopathological study of small lung cancer (diameter of 2 cm or less) by uptake value of 18F-fluorodeoxyglucose]. AB - 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) for lung cancer may be a biomarker for malignancy as well as a useful tool for detection of nodal involvement and distant metastasis. The goal of this study was to clarify a relationship between clinicopathological findings and maximum standardized uptake value( SUVmax) obtained by preoperative PET in patients with non-small cell lung cancer in diameter of 2 cm or less. Between January 2008 and April 2011, 124 patients( 54 men and 70 women) with non-small cell lung cancer in diameter of 2 cm or less undergoing lobectomy or segmentectomy were enrolled. The relationship between SUVmax and clinicopathological findings as tumor diameter, histological type, pleural invasion, vascular invasion, lymphatic permeation and nodal involvement were analyzed. Correlation between SUVmax and findings such as vascular invasion and lymphatic permeation showed relatively strong in the patients with adenocarcinoma, on the contrary to the correlation in the patients with non-adenocarcinoma. No tumor showing SUVmax of 2 or less showed vascular invasion and/or lymphatic permeation as well as nodal involvement in any patients with adenocarcinoma. SUVmax of the primary tumor in diameter of 2 cm or less, can be a useful biomarker which indicates a surgical candidate for sublobar pulmonary resection as well as mediastinal nodal dissection, especially in patients with adenocarcinoma. PMID- 22314153 TI - [Surgical management for lung cancer in less than 1 cm]. AB - Recently, the greater utilization of computed tomography (CT) has led to an increasing proportion of small-sized stage I A lung cancer in less than 1 cm in diameter. However, a treatment strategy for these small-sized lung cancers has not yet been defined. The aim of this study was to investigate surgical outcomes regarding these lung cancers. A total of 123 patients who underwent complete surgical resection for lung cancer in less than 1 cm between January 1995 and March 2010 were retrospectively evaluated. The 123 study subjects consisted of 54 male and 69 female patients. The mean age was 64.0 (43~82) years. The mean tumor size was 0.9( 0.3~1.0) cm. In this study, 70 patients underwent lobectomy (56.9%). Segmentectomy and wedge resection were underwent 23( 18.7%) and 30 patients( 24.4%), respectively. The 3-, 5- and 10-year survival rates were 95.7, 92.3 and 85.7%, respectively, after the operation for lung cancer in less than 1 cm. There were no significant difference between sublobar resection and lobectomy. However, 2 patients( 1.6%) had recurrent cancer and 7 patients (5.7%) had lymph node metastasis. We suggested surgical procedure for patients with lung cancers in less than 1 cm should be selected with the greatest care, because recurrent cancer and lymph node metastasis can occur in patients. PMID- 22314154 TI - [Clinical characteristics after surgery of non-small cell lung cancer which measures 20 mm or less in diameter]. AB - Today's advances in diagnostic image-technologies often enable us to find small lung cancers. However, we have few definite strategies including how to diagnosis and treat them. In this study, we performed a retrospective analysis of 122 consecutive patients who underwent surgery for non-small cell lung cancer 20 mm or less in diameter to clarify the clinical features of small lung cancer. Of 122 patients, there were 114 patients of pN0, and 8 patients with lymph node metastasis. Seventy three patients underwent lobectomy, 45 underwent segmentectomy, and 4 underwent wedge resection based on the findings of preoperative CT and anatomical and oncological view during operation. Overall survival rate( OS) and progression free survival( PFS) at 3-year was, 94% and 84%, respectively. There were no differences in OS or PFS between lobectomy group and limited resection group, which might suggest that we adapted appropriate surgical procedures. Multivariate analysis revealed that pathological pleural invasion, lymphatic vessel invasion, and vascular vessel invasion were likely to be unfavorable prognostic-factors. We believe that further investigations should be required to clarify the characteristics of small lung cancer. PMID- 22314155 TI - [Indication and results of thoracoscopic segmentectomy for small peripheral lung cancer]. AB - Since 2008, 46 patients have undergone thoracoscopic segmentectomy without mini thoracotomy for almost pure ground-glass opacity (GGO) lesion by thin-section computed tomography (CT) finding which was difficult to be performed wedge resection. No patient was converted to both thoracotomy and lobectomy. The operation time ranged from 75 to 240 min (mean, 161 min), and blood loss ranged from 1 to 110 g( mean, 25 g). We used stapler in 29 patients and electrocautery in 17 patients to deviate inter segmental plane. Postoperative complications were seen in 6 patients (13%), major complication was air leakage in 6 patients. There was no in-hospital mortality. Only 1 patient had bone metastasis on 11 months after operation. Thoracoscopic segmentectomy considered to be a safe and feasible procedure for the selected patients with small-sized peripheral lung cancer. PMID- 22314156 TI - [Clinical outcome after video-assisted thoracic surgery (VATS) for clinical stage I lung cancer with pathologically nodal involvement]. AB - The lymph node dissection with video-assisted thoracic surgery( VATS) was technically feasible and the remnant lymph nodes and tissues were 2% to 3%, which seems acceptable for clinical stage I lung cancer. Surgical outcome after VATS for clinical stage I lung cancer with pathologically nodal involvement, however, remains unclear. Medical records of 72 patients who had clinical stage I non small cell lung cancer with pathologically nodal involvement( pN1:21 patients, pN2:51 patients) and underwent VATS lobectomy or segmentectomy with mediastinal dissection between January 2005 and December 2010, were retrospectively reviewed. Postoperative recurrence and survival were studied. Remnant nodal recurrence occurred in 8 patients with pN1 (recurrence rate 38%) and 15 patients with pN2 (recurrence rate 29%). The 1- and 3-year disease free survival rate was 87% and 68%. The 1- and 3-year survival rate was 100% and 79%. This study suggested that VATS is acceptable for patients with clinical stage I lung in terms of survival rate, cancer with pN1. In a view point of remnant nodal recurrence, a more skillful dissection procedure is required. PMID- 22314157 TI - [Procedure for lung resection in patients with small-sized lung cancer and mid term results]. AB - Sublobar resection and the optimum approach for small-sized lung cancer remain controversial. We defined the criteria for the selection of cT1aN0M0 patients for thoracoscopic lung surgery and the criteria for other patients for open lung surgery in 2004. Limited resection for small-sized lung cancer was performed when the diameter of the solid lesion was less than 20% the diameter of lesions of groundglass opacity( GGO). The 5-year overall survival and 5-year disease-free survival( 5Y-DFS) was 89.9% and 91.7%, respectively. The 5Y-DFS according to the pathological stage was as follows:stage IA, 96.5%;IB, 100%;IIA, 50%;IIIA, 66.7%;and stage IV, 100%. According to computed tomography (CT) findings, the 5Y DFS was as follows:pure GGO lesion, 100%;mixed GGO lesion, 100%;and solid lesion, 84.6%. Lymph node metastases and recurrence were noticed only in patients with a solid lesion. Thus, patients with GGO lesions are considered good candidates for thoracoscopic sublobar resection. In addition, thoracoscopic segmentectomy was performed in cT1bN0M0 patients with GGO lesions, and good prognostic results were obtained;therefore, these patients are also considered good candidates for the procedure. PMID- 22314158 TI - [Indication of limited pulmonary resection for small-sized lung cancer based on preoperative clinical data]. AB - Limited pulmonary resection is performed mostly based on the size of lung cancer and ground-glass opacity (GGO). It has been proposed to determine the indication of segmentectomy according to hilar lymph node involvement. There is a potential risk of underestimation for lymph node involvement since there may be a skip mediastinal lymph node metastasis without hilar involvement. We propose to use standardized uptake value( SUV) max of primary lung cancer as an indicator of non invasive lung cancer. None of 44 small-sized lung cancers with SUVmax lower than 1 had lymph node metastasis or vessel invasion. A small-sized lung cancer <= 2 cm with SUVmax <= 1 is indicated wedge resection if GGO area is greater than 75% of tumor. Segmentectomy is indicated if the GGO area is less than 75%. We also propose selective lymphadenectomy for small-sized lung cancer. The lower mediastinal lymphadenectomy may be omitted if a small-sized tumor is located in the right upper lobe or the left upper segment. The upper mediastinal lymphadenectomy may be omitted if a small-sized lung cancer is located in the lower lobe and if the lower mediastinal lymph node involvement is excluded. PMID- 22314159 TI - [Surgical treatment of thoracoabdominal aortic aneurysm]. AB - Thoracoabdominal aortic aneurysm (TAAA) repair is the most invasive aortic surgery, requiring wide aortic exposure and reconstruction of branches of vital organs. Spinal cord ischemic injury( SCII) remains the most devastating complication. There has been a significant improvement in operative mortality and the incidence of SCII during past 2 decades in the treatment of TAAA repair. A number of adjuncts have been successfully used intraoperatively and postoperatively to minimize the risk of SCII. However, TAAA repair is a still surgical challenge for many cardiothoracic surgeons because there is no definite method to prevent SCII. As the cause of SCII has been considered to be multifactorial from many experimental and clinical studies, multidisciplinary approach is essential in the surgical treatment of TAAA. This review describes the recent advances and operative management of TAAA repair in the current era. PMID- 22314160 TI - [Single-stage procedure for multiple dissected aortic aneurysms with coagulopathy in an elderly patient]. AB - An 86-year-old man was admitted for abdominal pain. Dissected descending thoracic aortic aneurysm and infrarenal abdominal aortic aneurysm were observed under computed tomographic (CT) scan. Hematologic studies revealed low platelet count and an increase in fibrin degradation products (FDP), and disseminated intravascular coagulation( DIC) associated with dissecting aortic aneurysm was highly suspected. Platelet transfusion was performed and gabexate mesilate was administered, however, no improvement of DIC could be obtained. An increase in aortic diameter was observed under CT scan and surgery was performed. The infrarenal aneurysm was replaced with a bifurcated prosthetic graft under open repair. Simultaneously, an endovascular stent-graft was delivered from the left limb of the abdominal graft and implanted into the descending thoracic aorta. The postoperative recovery was uneventful but platelet count did not improve in this case. PMID- 22314161 TI - [Surgical therapy for ischemic cardiomyopathy]. AB - BACKGROUND: Surgical ventricular restoration (SVR) is considered as an effective surgical procedure for patients with ischemic myocardiopathy( ICM). However" surgical treatment for ischemic heart failure (STICH)" trial concluded that adding SVR to coronary artery bypass grafting (CABG) did not relieve symptoms and failed to lower death rate or cardiac rehospitalization as compared with CABG alone. AIM: The aim of this study was to investigate the efficacy of CABG with SVR for ICM. METHODS AND RESULTS: We retrospectively studied 24 patients who had undergone CABG with or with out SVR for ICM from October 1992 to June 2008. In CABG with SVR group, cardiac symptoms were relieved and the left ventricular end systolic volume index (LVESVI) was reduced from the baseline significantly. However cardiac symptoms were relieved only in CABG-S [left ventricular end diastolic dimension (LVDd)<60 mm] group, and not in CABG-L (LVDd>=60 mm) group. LVESVI was not reduced in CABG without SVR group. CONCLUSION: SVR contributed to relieving the symptoms, and improving the left ventricular function and the long term survival of patients with especially dilated ICM, which could not be achieved by CABG alone. PMID- 22314162 TI - [Surgical treatment of coronary aneurysm after percutaneous coronary intervention]. AB - A 61-year-old man with acute myocardial infarction underwent percutaneous coronary intervention with stent for the left main coronary artery (LMT) and the left anterior descending artery (LAD). Three months later, we recognized the LMT aneurysm complicated with possible thrombus formation, which developed in size during 6 months. In addition, the LAD stent showed significant in-stent stenosis. For the purpose of supplying blood flow to the distal of LAD, and avoiding myocardial infarction due to distal thrombosis possibly originated from LMT aneurysm, we decided to perform surgical operation. On preoperative examination, this patient had an obstruction of the right internal carotid artery. Although the direct repair of LMT aneurysm requires conventional approach with cardiopulmonary bypass, we applied off-pump coronary artery bypass grafting( OPCAB) considering the risk of cerebrovascular event. Consequently, OPCAB was performed in usual fashion [right internal thoracic artery (RITA) -LAD, left internal thoracic artery-left circumflex artery (LITA-LCX)] followed by the ligation of the proximal of LAD and LCX without cardiopulmonary bypass. The patient had a good operative course. PMID- 22314163 TI - [A review of cases of surgery for acute empyema]. AB - We retrospectively reviewed cases of acute empyema treated surgically in our hospital from April 2005 to April 2010. Patients comprised 10 men and 4 women, with a mean age of 62.5 years( range, 23~ 80 years). One case required open thoracotomy and decortication, and was in the organized phase at the time of operation( duration of symptoms before surgery, 44 days). The remaining 13 cases were in the fibropurulent phase at the time of operation and underwent video assisted thoracoscopic surgery (VATS). In 6 of these 13 remaining cases, we performed mini-thoracotomy combined with the thoracoscopic operation due to the presence of severe intrathoracic adhesions. Median durations of postoperative drainage and postoperative stay were 5 days( range, 2~7 days) and 13.5 days( range, 6~17 days), respectively. Postoperative complications of subcutaneous abscess, drug-induced hepatitis, pseudomembranous enterocolitis and reexpansion pulmonary edema were observed in 1 case each, but all patients survived to discharge without perioperative deaths. VATS is a safe and effective method for the management of acute empyema, and is favorable to perform in the fibropurulent phase. Appropriate combination with mini-thoracotomy was useful in accomplishing surgery in cases with dense adhesion. PMID- 22314164 TI - [Issues and indications for off-pump coronary artery bypass grafting]. AB - We have evaluated the usefulness of off-pump coronary artery bypass grafting (CABG)[OPCAB]. The subjects were 153 patients who underwent isolated CABG between May 2005 and May 2009. They were divided into 2 groups( on-pump/arrest;ON group:76 subjects vs OPCAB;OFF group:77 subjects). The concomitant conditions, the number of bypasses, the postoperative outcome and the early graft patency rate were compared between the 2 groups. The mean age and the incidence of carotid artery lesions were significantly higher in the OFF group. The number of bypasses was significantly smaller in the OFF group. The postoperative intubation time and the length of postoperative hospitalization were significantly shorter in the OFF group. Concerning major postoperative complications, mediastinitis, cerebral infarction or bleeding was not observed in the OFF group. There was no hospital death in the OFF group. The early graft patency rate with saphenous vein graft (SVG) was significantly lower in the OFF group. Early stage extubation was achieved by the introduction of OPCAB. In some occasions, however, the target site could not be reached with OPCAB, and furthermore, the quality of anastomosis was poor. In order to achieve complete revascularization, therefore, on pump/arrest surgery should be considered in some cases. PMID- 22314165 TI - [Infective endocarditis of the mitral valve complicated with preoperative rupture of the mycotic iliocolic artery aneurysm]. AB - A 55-year-old man was diagnosed with infective endocarditis( IE) of the mitral valve caused by Streptococcus sanguinis. His IE was controlled immediately after the initiation of intravenous antibiotic therapy lasting for 4 weeks. A few days before surgery, he complained of abdominal discomfort and computed tomography (CT) scan revealed rupture of the mycotic iliocolic artery aneurysm. Emergency transcatheter arterial embolization( TAE) was successfully conducted. After additional 4 weeks' intravenous antibiotic therapy, the mitral valve was replaced. Mycotic visceral artery aneurysms are rare in IE. Early diagnostic approaches and interventions such as TAE are crucial. PMID- 22314166 TI - [Retropharyngo-esophageal hematoma treated by open paramedian tracheostomy]. AB - Forty eight year-old woman with untreated liver cirrhosis was transferred to our critical care and emergency center because of airway crisis due to retropharyngo esophageal hematoma after slight chest contusion. We performed emergency tracheal intubation beyond stenotic part of the trachea. The hematoma did not diminished in a few days. Although we considered tracheostomy, we hesitated to perform conventional median tracheostomy because of the risk of complication of infection of the hematoma which might require drainage or removal resulting in contamination between tracheostomy site and cervical wound. We performed paramedian tracheostomy by antero-lateral skin incision to avoid these risks. Fortunately, the patient did not require drainage of the retropharyngo-esophageal hematoma. Paramedian tracheostomy should be taken into account for patients with presumably contaminated cervical wound. PMID- 22314167 TI - [Traumatic rupture of diaphragm with splenic injury]. AB - A 56-year-old woman admitted to our hospital because of injury by a road accident. A chest X-ray film and computed tomography (CT) scan showed multiple left rib fractures, hemothorax in the left pleural cavity, and obscurity of the left diaphragm. The stomach and injured spleen were also shown to shift to the left thoracic cavity. The patient was diagnosed as having diaphragmatic rupture with hemothorax in the left pleural cavity due to splenic injury. Emergent surgery was performed and massive bleeding was observed in the thoracic and abdominal cavities. After performing splenectomy and replacing the stomach in the abdominal cavity, the diaphragm was repaired. The patient was discharged 66 days after the surgery. Since traumatic diaphragm rupture can lead to hemorrhagic shock associated with injuries to adjacent organs, it is important to establish an accurate diagnosis and to performed appropriate surgical treatment without delay. PMID- 22314168 TI - [Successful treatment of aortoesophageal fistula due to a thoracic aortic aneurysm]. AB - A 78-year-old female presented at a nearby hospital with hemorrhage and loss of consciousness. After examination by computed tomography (CT) scan, she was referred to our hospital on suspicion of an impending rupture of the descending thoracic aorta aneurysm. She underwent a 2 stage operation. At the 1st operation, graft replacement of the descending aorta and closing of the aneurysmal wall over the aortoesophageal fistula were performed. On the 2nd postoperative day, intrathoracic esophagogastrostomy was performed by the gastric tube interposition technique. On the 54th postoperative day, she was discharged to a rehabilitation hospital. PMID- 22314169 TI - [Giant malignant solitary fibrous tumor successfully resected via clamshell incision and lower door open thoracotomy]. AB - We report a case of a giant intrathoracic tumor successfully resected via clamshell incision and lower door open thoracotomy. A 62-year-old woman presented with cough and dyspnea on exertion. A chest computed tomography (CT) revealed a giant mass occupying nearly whole of the right hemithorax. Since the tumor infiltrated deeply into the lung parenchyma, we performed a right pneumonectomy. The 1st thoracotomy was performed at 4th intercostal clamshell incision. Then we divided lower sternum vertically and opened the right lower chest wall laterally. These procedures provided wide operative view from the apex to the diaphragm and excellent access to hilar constructions, and enabled enbloc resction of giant tumor with the right lung. The resected specimen was 25*19*12 cm in size, 2,830 g in weight, and histologically diagnosed as a malignant solitary fibrous tumor. We conclude that this approach is effective for excision of giant intrathoracic tumor. PMID- 22314170 TI - [Open heart surgery in a patient with a history of Takotsubo cardiomyopathy]. AB - An 81-year-old man had a history of Takotsubo cardiomyopathy induced by general fatigue after travel and acute gastritis 2 years previously. Recently, dyspnea on effort had been worsening. Since preoperative echocardiography showed severe aortic valve regurgitation (AR) with left ventricular (LV) dilatation, aortic valve replacement (AVR) by the standard procedure was indicated. Since the safety of the perioperative clinical course including recurrence of Takotsubo syndrome and hemodynamic compromise was unclear, a thorough examination was performed before surgical intervention. AVR with a 21 mm Mosaic bioprosthesis was performed. Transesophageal echocardiography (TEE) during operation did not demonstrate any sign of Takotsubo syndrome and good LV function was maintained. The patient was discharged on postoperative day 18 without any cardiac events including arrhythmia or clinical symptoms such as chest pain. Based on these results, open heart surgery under cardiopulmonary bypass (CPB) and cardiac arrest could be safely performed in patients with a history of Takotsubo cardiomyopathy with minimum use of cardiac agents including cathecholamine and sufficient perioperative removal of emotional and physical stress. PMID- 22314171 TI - [Eosinophilic pleural effusion possibly induced by fibrin sealant]. AB - A 74-year-old man underwent right upper lobectomy for the lung cancer and bullectomy of right lower lobe. Fibrin sealant was used for sealing the excision line. The increase of the pleural effusion with increasing C-reactive protein( CRP) and eosinophilia was noted at the 17th day after the operation. The pleural effusion was transparent and yellowish colored suggesting transudatory liquid. The eosinophil in the pleural effusion was as high as 14%. The drainage of the pleural effusion was performed for 2 days resulting in disappearing the abnormal accumulation without any additional treatment. The cause of pleural effusion was supposed to be fibrin sealant by a positive result of the drug lymphocyte stimulation test. PMID- 22314172 TI - [Basic of wound healing in thoracic surgery]. AB - Wound condition changes from moment to moment. It is important to understand what is happening on the wound to evaluate and treat it. Wound can be classified into low contaminated wound, contaminated wound, colonized wound, critical colonized wound and infected wound by status of bacteria on the wound. Moreover, it can be classified into acute wound, subacute wound, subchronic wound, and chronic wound by time course. Also, wound healing course can be classified into coagulation phase, inflammation phase, proliferation phase and remodeling phase. Moreover, wound healing can be classified into primary wound healing, secondary wound healing and tertiary wound healing according to types of surgical intervention. The TIME principles provide a systematic approach to the management of wounds. TIME leads to an optimal wound bed preparation( WBP). The objectives underpinning TIME are tissue non-viable or deficient (T), infection or inflammation (I), moisture imbalance (M) and epidermal margin;non advancing or undermined( E). PMID- 22314173 TI - [Thoracic endovascular stent graft for late pseudoaneurysm formation after patch aortoplasty; report of a case]. AB - We report a case of a 51-year-old man presenting with pseudoaneurysm associated with a knitted Dacron patch used to repair coarctation of the aorta. At the age of 15 years, he underwent patch angioplasty for coarctation of the aorta. However the computed tomography( CT) scan, taken after 36 years, demonstrated pseudoaneurysm of the thoracic aorta at the anastmotic site. He was treated by endovascular stent graft using Gore-TAG 3115. His postoperative course was uneventful. Follow-up CT scan demonstrated no recurrence of pseudoaneurysm. PMID- 22314174 TI - [Persistent fifth aortic arch with coarctation of aorta; report of a case]. AB - Persistent 5th aortic arch (PFA) is a rare congenital cardiac anomaly that was firstly reported by Van Praagh et al, in 1969. A 3-month-old boy was referred to us with no symptom but heart murmur. Cardiac echocardiography and the following 3 dimensional computed tomography (3D-CT) scan revealed PFA with coarctation of aorta. There was pressure gradient of 50 mmHg between upper and lower limbs. He was carefully observed at the outpatient clinic because of no afterload mismatch. At the age of 9 months, coarctectomy and end-to-end anastomosis was performed between the PFA and distal arch below left vertebral artery. A histological examination of resected tissue revealed the thickened intima and rough elastic fiber that is absolutely different from normal aorta. Careful observation is necessary with the possibility of future aneurysmal change or re-coarctation, although the postoperative course has been so far uneventful. PMID- 22314175 TI - [Severe intestinal ischemia due to chronic aortic dissection; report of a case]. AB - We report a rare case with severe intestinal ischemia due to chronic aortic dissection. A 75-year-old man was admitted to our hospital with abdominal and right leg pain. The patient had a history of aortic dissection (Stanford type B) 12 years before admission and had been treated medically. Although a throaco abdominal aneurysm due to aortic dissection (Crowford type III) had been diagnosed 1 year before admission, he had rejected the operation. Computed tomography (CT) revealed an increased diameter of the aneurysm (6 cm). As abdominal pain was increased, emergent surgery was performed on day 1 after admission. Although perfusion of the superior mesenteric artery and marginal artery was maintained, intestinal ischemia was worsening and general condition was deteriorated during surgery. Bypass surgery and/or resection of colon were not indicated because of peripheral colon artery ischemia, and he expired day 1 after surgery. PMID- 22314176 TI - [Rectal metastasis from lung cancer; report of a case]. AB - A 70-year-old male underwent left pneumonectomy for lung cancer in November 2008. Although he was diagnosed as pT2bN1M0 (stage II B) after the operation, adrenal metastasis was found 8 months later. Positron emission tomography (PET) revealed accumulation in the adrenal gland and rectum. Gastrointestinal tract examination revealed a type 1 tumor in the rectum. Histological examination of biopsy specimens obtained from the lesion suggested papillary adenocarcinoma of rectum. Abdominoperineal resection was performed. The resected rectal tumor was reported immunohistochemically as metastasis from primary lung cancer. PMID- 22314177 TI - [Pleuroperitoneal communication detected at the beginning of continuous ambulatory peritoneal dialysis; report of a case]. AB - A 61-year-old female was diagnosed as having end-stage renal failure developed dyspnea soon after introduction of continuous ambulatory peritoneal dialysis (CAPD). Chest X-ray showed a right-side massive pleural effusion. Pleuro peritoneal communication was suspicious, because the hydrothorax significantly improved by the stop of CAPD. We performed video-assisted thoracic surgery. Using indigo carmine containing peritoneal dialysis fluid through a CAPD catheter, we found a fistula on the diaphragm from which blue dialysis solution flowed out like a fountain. The fistula of the diaphragm was directly closed with a surgical stapler and covered using cellulose oxidized (Surgicel) and fibrin glue. She could restart CAPD on postoperative days 7, and no recurrence of hydrothorax has been detected for 10 months after surgical treatment. PMID- 22314178 TI - Breast cancer risk prediction and individualised screening based on common genetic variation and breast density measurement. AB - INTRODUCTION: Over the last decade several breast cancer risk alleles have been identified which has led to an increased interest in individualised risk prediction for clinical purposes. METHODS: We investigate the performance of an up-to-date 18 breast cancer risk single-nucleotide polymorphisms (SNPs), together with mammographic percentage density (PD), body mass index (BMI) and clinical risk factors in predicting absolute risk of breast cancer, empirically, in a well characterised Swedish case-control study of postmenopausal women. We examined the efficiency of various prediction models at a population level for individualised screening by extending a recently proposed analytical approach for estimating number of cases captured. RESULTS: The performance of a risk prediction model based on an initial set of seven breast cancer risk SNPs is improved by additionally including eleven more recently established breast cancer risk SNPs (P = 4.69 * 10-4). Adding mammographic PD, BMI and all 18 SNPs to a Swedish Gail model improved the discriminatory accuracy (the AUC statistic) from 55% to 62%. The net reclassification improvement was used to assess improvement in classification of women into low, intermediate, and high categories of 5-year risk (P = 8.93 * 10-9). For scenarios we considered, we estimated that an individualised screening strategy based on risk models incorporating clinical risk factors, mammographic density and SNPs, captures 10% more cases than a screening strategy using the same resources, based on age alone. Estimates of numbers of cases captured by screening stratified by age provide insight into how individualised screening programs might appear in practice. CONCLUSIONS: Taken together, genetic risk factors and mammographic density offer moderate improvements to clinical risk factor models for predicting breast cancer. PMID- 22314179 TI - Problem solving in relation to resources in everyday life in families of children with disabilities: a pilot study. AB - Problem solving is recognized as a skill, helping families of children with disabilities to manage problems in everyday life. Family problem-solving skills may therefore be seen as an important outcome of a child and youth habilitation service. The aim of this pilot feasibility study was to examine the design of a future web-based questionnaire study focusing on problem-solving patterns in relation to resources in families of children with disabilities. The descriptive statistical analyses built on data from 13 families and findings showed an overall satisfactory score distribution for three of the included instruments, whereas two instruments showed floor effects in one third of the items. Findings indicated design problems with data collection related to adapting questionnaires to a web-based survey format and to problems with the stop function that was added. Implementing the main study using web-based surveys needs critical considerations according to the choice of the web tool and the recruitment process. PMID- 22314180 TI - Organizing care for persons with psychotic disorders and risk of or existing diabetes mellitus type 2. AB - This literature review aimed to explore previous knowledge about specific care requirements for persons with psychotic disorders and risk of or existing type 2 diabetes. Sixteen qualitative and quantitative studies in the area were identified and summarized. The studies together indicate that mental health nurses play an important role in motivating people to perform diabetes care as they are often known to and trusted by the patients. A holistic approach to the person's health, with close follow-ups by psychiatric care and cooperation with diabetes care, may have benefits for the person with diabetes. Screening for and treating psychotic symptoms is an important task for the mental health nurse, as these symptoms drain energy from the person and prevent diabetes self-care. Lifestyle and diabetes education needs to be practical, adapted to the individual and focused on maintaining a healthy diet, regular exercise, changing smoking habits and preventing diabetes complications. Treatment with antipsychotic drugs increases the need for follow-ups of glycaemic control. PMID- 22314181 TI - Cell polarity in myelinating glia: from membrane flow to diffusion barriers. AB - Myelin-forming glia are highly polarized cells that synthesize as an extension of their plasma membrane, a multilayered myelin membrane sheath, with a unique protein and lipid composition. In most cells polarity is established by the polarized exocytosis of membrane vesicles to the distinct plasma membrane domains. Since myelin is composed of a stack of tightly packed membrane layers that do not leave sufficient space for the vesicular trafficking, we hypothesize that myelin does not use polarized exocytosis as a primary mechanism, but rather depends on lateral transport of membrane components in the plasma membrane. We suggest a model in which vesicle-mediated transport is confined to the cytoplasmic channels, from where transport to the compacted areas occurs by lateral flow of cargo within the plasma membrane. A diffusion barrier that is formed by MBP and the two adjacent cytoplasmic leaflets of the myelin bilayers acts a molecular sieve and regulates the flow of the components. Finally, we highlight potential mechanism that may contribute to the assembly of specific lipids within myelin. This article is part of a Special Issue entitled Lipids and Vesicular Transport. PMID- 22314182 TI - Chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities. The main cause is smoking tobacco, but other factors have been identified. Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli. The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both. Comorbidities include ischaemic heart disease, diabetes, and lung cancer. Bronchodilators constitute the mainstay of treatment: beta(2) agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids). Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification. Future research should be directed towards the development of agents that notably affect the course of disease. PMID- 22314183 TI - Colorectal poorly differentiated neuroendocrine carcinomas and mixed adenoneuroendocrine carcinomas: insights into the diagnostic immunophenotype, assessment of methylation profile, and search for prognostic markers. AB - Colorectal poorly differentiated neuroendocrine carcinomas (NECs) and mixed adenoneuroendocrine carcinomas (MANECs) are well-recognized entities generally known to be associated with biological aggressiveness and poor patient survival. However, a few published papers have highlighted the existence of a subgroup of tumors with a better survival than expected; however, to date, there are no established parameters that usefully identify this category. In the present study we have investigated the morphologic features, the CpG methylator phenotype (CIMP), microsatellite instability (MSI), and the immunohistochemical profile, including the expression of transcription factors (TTF1, ASH1, CDX2, and PAX5), stem cell markers (CD117 and CD34), and cytokeratins 7 and 20, in a series of 39 carcinomas (27 NECs and 12 MANECs) to better characterize such neoplasms and to search for prognostic indicators. No different patient survival was observed between NECs and MANECs. Neoplasms showed a heterogenous spectrum of morphologic and immunohistochemical features; however, only large-cell subtype, significant peritumoral lymphoid reaction, CD117 immunoreactivity, vascular invasion, and MSI/CIMP+ status were significantly correlated with prognosis on univariable analysis. Furthermore, vascular invasion and CD117 immunoreactivity were independent prognostic markers on multivariable analysis. In addition to these prognostic features, neoplasms showed different expression of transcription factors, stem cell markers, and cytokeratins that should be considered for diagnostic purposes and, especially, for discriminating among possible differential diagnoses. PMID- 22314184 TI - The 3-layered ductal epithelium in gynecomastia. AB - Gynecomastia is the most common abnormality in the male breast and has been associated with male breast cancer, but whether there is an etiological role remains unknown. In the present study we conducted an immunohistochemical investigation to further characterize gynecomastia. A total of 46 cases of gynecomastia were immunohistochemically stained on tissue microarrays for estrogen receptor (ER), progesterone receptor, HER2, androgen receptor, cytokeratins (CK5, CK14, CK7, and CK8/18), p63, E-cadherin, BRST2, cyclin D1, Bcl 2, p53, p16, p21, and Ki67. In addition, 8 cases of male ductal carcinoma in situ and normal breast tissue obtained from autopsies (n=10) and adjacent to male breast cancer (n=5) were studied. Normal ductal male breast epithelial cells were very often ER and Bcl-2 positive (>69%), and progesterone receptor and androgen receptor expression was also common (>39%). Gynecomastia showed a consistent 3 layered pattern: 1 myoepithelial and 2 epithelial cell layers with a distinctive immunohistochemical staining pattern. The intermediate luminal layer, consisting of vertically oriented cuboidal-to-columnar cells, is hormone receptor positive and expresses Bcl-2 and cyclin D1. The inner luminal layer is composed of smaller cells expressing CK5 and often CK14 but is usually negative for hormone receptors and Bcl-2. Male ductal carcinoma in situ was consistently ER positive and CK5/CK14 negative. In conclusion, for the first time we describe the 3-layered ductal epithelium in gynecomastia, which has a distinctive immunohistochemical profile. These results indicate that different cellular compartments exist in gynecomastia, and therefore gynecomastia does not seem to be an obligate precursor lesion of male breast cancer. PMID- 22314185 TI - Vascular endothelial growth factor receptor 2 as a marker for malignant vascular tumors and mesothelioma: an immunohistochemical study of 262 vascular endothelial and 1640 nonvascular tumors. AB - Vascular endothelial growth factor receptor 2 (VEGFR2) is a primary responder to vascular endothelial growth factor signal and thereby regulates endothelial migration and proliferation. This receptor is expressed in endothelial cells and in some vascular tumors, but many reports also detail its expression in carcinomas and lymphomas. VEGFR2 is a potential cell-type marker, and data on VEGFR2 expression may also have therapeutic significance in view of recent availability of VEGFR2 inhibitors. In this study, we immunohistochemically examined 262 vascular endothelial and 1640 nonvascular tumors and selected non neoplastic tissues with a VEGFR2-specific rabbit monoclonal antibody 55B11. In early human embryo, VEFGR2 was expressed in endothelia of developing capillaries and in the thoracic duct, great vessels, hepatic sinusoids, epidermis, and mesothelia. In late first trimester fetus peripheral soft tissues, VEGFR2 was restricted to capillary endothelia, chondrocytes, and superficial portion of the epidermis. In normal adult tissues, it was restricted to endothelia and mesothelia. VEGFR2 was consistently expressed in angiosarcomas, Kaposi sarcomas, and retiform hemangioendotheliomas. It was detected in only half of epithelioid hemangioendotheliomas (15/27), usually focally. VEGFR2 was strongly expressed in most capillary hemangiomas and weakly or focally in cavernous, venous, and spindle cell hemangiomas and in lymphangiomas. Malignant epithelial mesothelioma was found to be a unique epithelial neoplasm with a strong and nearly consistent VEGFR2 expression, including membrane staining (35/38). Approximately 10% of squamous cell carcinomas and 23% of pulmonary adenocarcinomas contained focal positivity. The only nonendothelial mesenchymal tumors found to be VEGFR2 positive were biphasic synovial sarcoma (focal epithelial expression) and chordoma. All melanomas and lymphomas were negative. VEGFR2 is a promising marker for malignant vascular tumors and malignant epithelioid mesothelioma. Expression in biphasic synovial sarcoma epithelium, chordoma, and some carcinomas has to be considered in differential diagnosis. Information on VEGFR2 tissue expression may be useful in development of targeted oncologic therapy through VEGFR2-specific tyrosine kinase inhibitors. PMID- 22314186 TI - Papillary lesions of the breast: impact of breast pathology subspecialization on core biopsy and excision diagnoses. AB - BACKGROUND: Classifying papillary lesions of the breast on core biopsy (CB) is challenging. Although traditionally all such lesions were surgically excised, at present, conservative management of benign lesions is being advocated; therefore, accurately classifying papillary lesions on CB is all the more imperative. The extent to which subspecialty training in breast pathology might mitigate such difficulties in diagnosis has not yet been reported. We investigated change in diagnoses from CB to surgical excision according to subspecialist training in breast pathology and interobserver agreement between specialized breast pathologists (BPs) and nonbreast pathologists (NBPs) in classifying these lesions. DESIGN: CBs of 281 papillary lesions from 266 patients diagnosed between 2000 and 2010 were classified by both a BP and NBP into benign, atypical, ductal carcinoma in situ/encapsulated papillary carcinoma, or invasive carcinoma categories. Rates of change in diagnostic category in the surgical excision specimen were calculated on the basis of: (i) the original diagnosis, (ii) diagnosis made by the BP, and (iii) diagnosis made by the NBP. Comparisons were made using the chi test. Kappa values were calculated for interobserver agreement. RESULTS: Of 162 lesions with subsequent excision, 90 were originally diagnosed as benign, 38 as atypical, 25 as ductal carcinoma in situ/encapsulated papillary carcinoma, and 9 as invasive on CB. The upgrade rate for benign papillomas to an atypical or malignant lesion on surgical excision was 22.2% according to the original diagnosis. This rate fell to 16.3% when the BP diagnoses were considered, compared with 26.3% for the NBP diagnoses. There was no significant difference between BPs and NBPs in the rate of upgrade from a benign to an atypical/malignant diagnosis, although downgrades from atypical/malignant to benign papillomas were more commonly seen among NBPs (P=0.002). Overall, the BP diagnosis on CB was less likely to differ from the excision diagnosis (P=0.0001). Benign papillomas upgraded on excision were more likely to occur with larger radiologic mass size (P=0.033) compared with those that were not upgraded. Of 8 benign papillomas upgraded to a malignant lesion on excision, 7 were discordant on radiology. Interobserver agreement between BP and NBP diagnoses was in the "fair agreement" range (kappa=0.38), with perfect agreement in 66.4% of cases. CONCLUSIONS: Correlation between CB and excision diagnoses for breast papillary lesions is significantly greater for BPs than for NBPs. This is largely because of a tendency to overcall atypia or malignancy on CB by NBPs. However, upgrades from benign to atypical or malignant did not significantly differ according to subspecialization. With accurate pathologic assessment and radiologic-pathologic correlation, the upgrade rate of benign papillomas to malignancy can be minimized significantly. PMID- 22314187 TI - Lymphoid hyperplasia and eosinophilic pneumonia as histologic manifestations of amiodarone-induced lung toxicity. AB - Amiodarone use is often limited by pulmonary toxicity. Amiodarone lung disease (ALD) classically manifests as organizing pneumonia with intra-alveolar foamy macrophages, but other patterns may also occur. Here we report 2 previously unreported patterns of ALD: lymphoid hyperplasia (LH) and eosinophilic pneumonia (EP). We identified patients with LH or EP as a prominent feature among 75 cases of probable ALD from the authors' teaching files collected from 1997 to 2010. Clinical history and lung wedge biopsies were reviewed. Twelve patients (7 men) met inclusion criteria (median age, 71 y). The exact amiodarone dose was known in all cases (median, 200 mg/d). Treatment duration was known in 10 cases and ranged from 1 to 12 years. Thoracic imaging showed diffuse infiltrates causing concern for a diagnosis of ALD. Histologic review revealed intra-alveolar foamy macrophages in all cases. Eight cases prominently displayed patterns of LH, including diffuse LH (7), follicular bronchiolitis (5), lymphoid interstitial pneumonia (2), and lymphocytic perivascular cuffing (2). Two showed features of acute EP, including diffuse alveolar damage with abundant eosinophils. Two showed features of chronic EP, including interstitial pneumonia with abundant eosinophils, patchy organization, and fibrinous exudates with macrophages and eosinophils. One chronic EP case also showed focal LH. Additional features included intra-alveolar giant cells (6), pleuritis (3), small poorly formed granulomas (3), and thrombi (2). LH and EP are previously unrecognized histopathologic manifestations of ALD, and amiodarone exposure should be included in their differential diagnosis. PMID- 22314188 TI - BRAF-mutated, microsatellite-stable adenocarcinoma of the proximal colon: an aggressive adenocarcinoma with poor survival, mucinous differentiation, and adverse morphologic features. AB - The association of BRAF V600E mutation and the presence of the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) often confound analysis of BRAF mutation status and survival in colorectal carcinoma. We evaluated a consecutive series of proximal colonic adenocarcinomas for mismatch repair protein abnormalities/MSI, BRAF V600E mutation, and KRAS mutations in an attempt to determine the prognostic significance of these abnormalities and to correlate histopathologic features with molecular alterations. Of the 259 proximal colon adenocarcinomas analyzed for mismatch repair protein abnormalities and/or MSI, 181 proximal colonic adenocarcinomas demonstrated proficient DNA mismatch repair using either MSI PCR (n=78), mismatch repair protein immunohistochemistry (n=91), or both MSI PCR and mismatch repair immunohistochemistry (n=12); these were tested for the BRAF V600E mutation and KRAS mutations. Compared with BRAF wild-type adenocarcinomas, BRAF-mutated adenocarcinomas more frequently demonstrated adverse histologic features such as lymphatic invasion (16/20, 80% vs. 75/161, 47%; P=0.008), mean number of lymph node metastases (4.5 vs. 2.2; P=0.01), perineural invasion (8/20, 40% vs. 13/161, 8%; P=0.0004), and high tumor budding (16/20, 80% vs. 83/161, 52%; P=0.02). BRAF mutated adenocarcinomas frequently contained areas with mucinous histology (P=0.0002) and signet ring histology (P=0.03), compared with KRAS-mutated and KRAS/BRAF wild-type adenocarcinomas. Clinical follow-up data were available for 173 proximal colonic adenocarcinomas with proficient DNA mismatch repair. Patients with BRAF-mutated adenocarcinomas had a median survival of 12.3 months with a 1-year probability of survival of 54% and a 1-year disease-free survival of 56%. Patients with KRAS-mutated and KRAS/BRAF wild-type adenocarcinomas had significantly improved overall survival (unadjusted log-rank P=0.03 and unadjusted log-rank P=0.0002, respectively) and disease-free survival (unadjusted log-rank P=0.02 and unadjusted log-rank P=0.02, respectively) compared with patients with BRAF-mutated adenocarcinomas. When adjusting for tumor stage, survival analysis demonstrated that patients with BRAF-mutated adenocarcinoma had a significantly poor overall survival and disease-free survival (hazard ratios 6.63, 95% CI, 2.60-16.94; and 6.08, 95% CI, 2.11-17.56, respectively) compared with patients with KRAS/BRAF wild-type adenocarcinomas. No significant difference in overall or disease-free survival was identified between patients with KRAS mutated and KRAS/BRAF wild-type adenocarcinomas. Our results demonstrate that BRAF-mutated proximal colon adenocarcinomas with proficient DNA mismatch repair have a dismal prognosis with an aggressive clinical course and often display mucinous differentiation, focal signet ring histology, and other adverse histologic features such as lymphatic and perineural invasion and high tumor budding. PMID- 22314189 TI - Extranodal NK/T-cell lymphoma, nasal type, includes cases of natural killer cell and alphabeta, gammadelta, and alphabeta/gammadelta T-cell origin: a comprehensive clinicopathologic and phenotypic study. AB - Extranodal NK/T-cell lymphoma (ENKTL), nasal type, may be of NK or T-cell origin; however, the proportion of T-ENKTLs and whether they are of alphabeta or gammadelta type remains uncertain. To elucidate the cell of origin and detailed phenotype of ENKTL and assess any clinicopathologic associations, 67 cases of ENKTL from Thailand were investigated, together with 5 gammadelta enteropathy associated T-cell lymphomas (EATLs) for comparison. In all, 70% of the ENKTL were T-cell receptor (TCR) beta,gamma and, in cases tested, delta negative (presumptive NK origin); 5% were TCR gammadelta, 3% were TCR alphabeta, 1% were TCR alphabeta/gammadelta, and 21% were indeterminate. Out of 17 presumptive NK ENKTLs tested, 3 had clonal TCR rearrangements. All cases were EBV and TIA-1; >85% were positive for CD3, CD2, granzyme B, pSTAT3, and Lsk/MATK; and all were CD16. Presumptive NK-ENKTLs had significantly more frequent CD56 (83% vs. 33%) and CXCL13 (59% vs. 0%) but less frequent PD-1 (0% vs. 40%) compared with T ENKTLs. Of the NK-ENKTLs, 38% were Oct-2 compared with 0% of T-ENKTLs, and 54% were IRF4/MUM1 compared with 20% of T-ENKTLs. Only alphabeta T-ENKTLs were CD5. Intestinal ENKTLs were EBV and had significantly more frequent CD30, pSTAT3, and IRF4/MUM1 expression but less frequent CD16 compared with gammadelta EATL. Significant adverse prognostic indicators included a primary non-upper aerodigestive tract site, high stage, bone marrow involvement, International Prognostic Index >=2, lack of radiotherapy, Ki67 >40%, and CD25 expression. The upper aerodigestive tract ENKTLs of T-cell origin compared with those of presumptive NK origin showed a trend for better survival. Thus, at least 11% of evaluable ENKTLs are of T-cell origin. Although T-ENKTLs have phenotypic and some possible clinical differences, they share many similarities with ENKTLs that lack TCR expression and are distinct from intestinal gammadelta EATL. PMID- 22314190 TI - Gastric HER2 Testing Study (GaTHER): an evaluation of gastric/gastroesophageal junction cancer testing accuracy in Australia. AB - Trastuzumab provides a survival benefit in patients with human epidermal growth factor receptor 2 (HER2)-amplified/overexpressed advanced gastric and gastroesophageal junction cancers (GC/GJCs). However, the optimal method for testing is unclear. The aim of this study was to assess interlaboratory agreement on HER2 scoring in GC/GJC to aid the development of a robust testing algorithm for diagnostic practice in Australia. Nine laboratories assessed the HER2 status of 100 GC/GJC tissue samples by immunohistochemistry (IHC) and in situ hybridization (ISH) [chromogenic (CISH) or silver (SISH)] using both HER2 copy number and HER2:chr17 (chromosome 17) ratio. Results were compared with reference fluorescence ISH (FISH). Interlaboratory agreement on IHC3+ scoring was good (kappa=0.76), and there was good/very good agreement between IHC (positivity defined as IHC3+) and ISH when HER2 copy number was used (kappa=0.72 to 0.87). Agreement on CISH/SISH scoring was good/very good when HER2 copy number was used (kappa=0.68 to 0.86), and agreement between CISH/SISH and FISH using HER2 copy number was very good (kappa=0.88 to 0.91). Agreement was reduced when HER2:chr17 ratio was used. The good agreement for HER2 copy number determined by bright field ISH suggests that this is the optimal method for testing in GC/GJC cases. An IHC3+ score was strongly predictive of a positive ISH result, although agreement for all IHC scores was only moderate, suggesting that IHC triage before ISH testing would be the most cost-effective strategy. However, because of the unique features of GC/GJC samples and the difficulty of ensuring consistent HER2 staining in the community setting, it is recommended that HER2 status in advanced GC/GJC be determined by both IHC and ISH in the same laboratory. PMID- 22314191 TI - High levels of nuclear MYC protein predict the presence of MYC rearrangement in diffuse large B-cell lymphoma. AB - Determining the presence of MYC gene rearrangements is becoming an increasingly important part of the diagnostic workup in aggressive lymphoma. Cytogenetic MYC alterations aid in differentiating diffuse large B-cell lymphoma (DLBCL) from Burkitt lymphoma. In addition, MYC aberrations are associated with poor prognosis in DLBCL. Fluorescence in situ hybridization and karyotyping are standard tests for detecting MYC aberrations, but these techniques are laborious and expensive. Here, we studied MYC status of 219 DLBCLs and Burkitt lymphomas using fluorescence in situ hybridization, immunohistochemistry, and quantitative real time polymerase chain reaction (QRT-PCR). Overall, 15% of the cases had an MYC break. QRT-PCR analysis of MYC expression showed that 72% of DLBCLs with an MYC break had aberrantly high or low levels of MYC transcript. Excluding the cases with aberrantly low MYC expression, we found a significant positive correlation between levels of MYC transcripts and MYC tumor cells; however, QRT-PCR is not readily applicable as a screening tool. Immunohistochemically, all tumors showed a nuclear staining pattern that was simple to evaluate. The percentage of MYC lymphoma cells correlated closely with MYC rearrangement status. In all, 93% of cases with an MYC break had >=80% MYC cells, in contrast to 3% of nonrearranged cases (P<0.0001). Receiver operating characteristic curve analysis showed >=70% MYC tumor cells to be the optimal cutoff (sensitivity=100%, specificity=93%). Area under the receiver operating characteristic curve was 0.992, indicating that immunostaining for Myc protein is an excellent screening test to predict whether an MYC rearrangement is present. PMID- 22314192 TI - Insulin-sensitizing properties of adiponectin. AB - Adiponectin administration improves glucose tolerance in rodents. This is due to both reductions in hepatic glucose production, and likely improved insulin stimulated glucose disposal in skeletal muscle. Adiponectin's effects in both liver and muscle are believed to be due in large part to AMP-activated protein kinase (AMPK) activation, resulting in a reduction in hepatic gluconeogenic enzymes and increased fatty acid oxidation and reduced ectopic lipid deposition in muscle. In addition, adiponectin can robustly stimulate mitochondrial biogenesis, at least in muscle, and this appears to be due to AMPK-independent mechanisms. Various treatments successful at improving insulin response (thiazolidinediones (TZDs), n-3 polyunsaturated fatty acid (PUFA) supplementation) also stimulate adiponectin production. Obesity and insulin resistance are often characterized by both a state of resistance to adiponectin (both liver and muscle), as well as a reduction in total circulating adiponectin concentrations. The mechanisms underlying the impaired response of muscle and liver to adiponectin have not been clearly elucidated. Surprisingly, the significance of adiponectin resistance, at least in muscle, is not entirely clear. While the development of adiponectin resistance precedes intramuscular lipid accumulation and impaired insulin response in high-fat fed rodents, the restoration of adiponectin response does not appear to be necessary in order to restore insulin response in muscle. Further research examining the cellular mechanisms underlying the development of adiponectin resistance, and the importance of treating this, needs to be conducted. PMID- 22314193 TI - Puerarin attenuates endothelial insulin resistance through inhibition of inflammatory response in an IKKbeta/IRS-1-dependent manner. AB - Puerarin is an isoflavonoid isolated from the root of the plant Pueraria lobata and has been used as a prescribed drug in China for the treatment of cardiovascular diseases in the clinical practice. Puerarin possesses potential therapeutic activities for metabolic and cardiovascular disorders. However, little is yet known about its bioprotection against endothelial dysfunction insulin resistance involved. In this study, we established insulin resistance by palmitate stimulation in the endothelium and investigated the action of puerarin on the modulation of insulin sensitivity under the insulin resistant condition. Palmitate stimulation impaired insulin-mediated vasodilation in the rat aorta and puerarin treatment effectively restored the impaired vasodilation in a concentration-dependent manner (1, 10 and 50 MUM). Palmitate stimulation evoked inflammatory response in endothelial cells. Puerarin inhibited IKKbeta/NF-kappaB activation and decreased TNF-alpha and IL-6 production with the downregulation of relative gene overexpression. Palmitate stimulation impaired the insulin PI3K signaling pathway and reduced insulin-mediated NO production in endothelial cells. Puerarin attenuated PA-induced phosphorylation of insulin receptor substrate-1 (IRS-1) at S307 and effectively ameliorated insulin-mediated tyrosine phosphorylation of IRS-1. The beneficial modification of serine/tyrosine phosphorylation of IRS-1 restored downstream Akt/eNOS activation, and thereby increased insulin-mediated NO production. These results suggest that puerarin inhibits inflammation and attenuates endothelial insulin resistance in an IKKbeta/IRS-1-dependent manner. PMID- 22314194 TI - Toxicities effects of pharmaceutical, olive mill and textile wastewaters before and after degradation by Pseudomonas putida mt-2. AB - BACKGROUND: Removal of numerous classes of chemical pollutants from the industrial wastewater such as textile, pharmaceutical and olive mill using conventional wastewater treatment, is incomplete and several studies suggested that improvement of this situation would require the application of biological treatment techniques. Dyes, polyphenols and drugs are an environmental pollutants extremely toxics to plants and other living organisms including humans. These effluents were previously treated by Pseudomonas putida. The main of this work was to evaluate the in vivo toxicity of the three wastewaters. METHODS: Writhes and convulsant effect of effluents were carried out and were compared to the treated effluents. Only pharmaceutical wastewater was exhibited a convulsant effect which observed in mice treated by effluent. On the other hand, all industrial wastewater induced significantly an algogenic effects particularly when mice were treated by the pharmaceutical wastewater (Number of writhes = 44). CONCLUSION: Toxicity was totally removed when mice were treated by the bio remediated effluent. This indicates that P. putida was able to completely detoxify the toxic industrial effluent. PMID- 22314195 TI - Usefulness of Choline-PET for the detection of residual hemangiopericytoma in the skull base: comparison with FDG-PET. AB - BACKGROUND: Choline is a new PET tracer that is useful for the detection of malignant tumor. Choline is a precursor of the biosynthesis of phosphatidylcholine, a major phospholipid in the cell membrane of eukaryotic cells. Malignant tumors have an elevated level of phosphatidylcholine in cell membrane. Thus, choline is a marker of tumor malignancy. METHOD: The patient was a 51-year-old man with repeated recurrent hemangiopericytoma in the skull base. We performed Choline-PET in this patient after various treatments and compared findings with those of FDG-PET. RESULTS: Choline accumulated in this tumor, but FDG did not accumulate. We diagnosed this tumor as residual hemangiopericytoma and performed the resection of the residual tumor. FDG-PET is not appropriate for skull base tumor detection because uptake in the brain is very strong. CONCLUSION: We emphasize the usefulness of Choline-PET for the detection of residual hemangiopericytoma in the skull base after various treatments, compared with FDG-PET. PMID- 22314196 TI - Role of vitamin D-binding protein in isocyanate-induced occupational asthma. AB - The development of a serological marker for early diagnosis of isocyanate-induced occupational asthma (isocyanate-OA) may improve clinical outcome. Our previous proteomic study found that expression of vitamin D-binding protein (VDBP) was upregulated in the patients with isocyanate-OA. In the present study, we evaluated the clinical relevance of VDBP as a serological marker in screening for isocyanate-OA among exposed workers and its role in the pathogenesis of isocyanate-OA. Three study groups including 61 patients with isocyanate-OA (group I), 180 asymptomatic exposed controls (AECs, group II), 58 unexposed healthy controls (NCs, group III) were enrolled in this study. The baseline serum VDBP level was significantly higher in group I compared with groups II and III. The sensitivity and specificity for predicting the phenotype of isocyanate-OA with VDBP were 69% and 81%, respectively. The group I subjects with high VDBP (>=311 MUg/ml) had significantly lower PC(20) methacholine levels than did subjects with low VDBP. The in vitro studies showed that TDI suppressed the uptake of VDBP into RLE-6TN cells, which was mediated by the downregulation of megalin, an endocytic receptor of the 25-hydroxycholecalciferol-VDBP complex. Furthermore, toluene diisocyanate (TDI) increased VEGF production and secretion from this epithelial cells by suppression of 1,25-dihydroxycholecalciferol [1,25(OH)(2)D(3)] production. The findings of this study suggest that the serum VDBP level may be used as a serological marker for the detection of isocyanate-OA among workers exposed to isocyanate. The TDI-induced VEGF production/ secretion was reversed by 1,25(OH)(2)D(3) treatment, which may provide a potential therapeutic strategy for patients with isocyanate-OA. PMID- 22314197 TI - Platelet-rich plasma inhibits the apoptosis of highly adipogenic homogeneous preadipocytes in an in vitro culture system. AB - Auto-transplantation of adipose tissue is commonly used for the treatment of tissue defects in plastic surgery. The survival of the transplanted adipose tissue is not always constant, and one of reasons is the accelerated apoptosis of the implanted preadipocytes. We have recently established highly homogeneous preadipocytes, named ccdPAs. The aim of the current study was to evaluate the regulation of the potency of platelet-rich plasma (PRP) on the apoptosis of ccdPAs in vitro. PRP stimulated the proliferation of the preadipocytes in a dose dependent manner, and the stimulatory activity of 2% PRP was significantly higher than that of 2% FBS or 2% platelet-poor plasma (PPP). The presence of 2% PRP significantly inhibited serum starvation- or TNF-alpha/cycloheximide-induced apoptosis in comparison to 2% FBS or 2% PPP. DAPK1 and Bcl-2-interacting mediator of cell death (BIM) mRNAs were reduced in the preadipocytes cultured with 2% PRP in comparison to those cultured in 2% FBS. The gene expression levels were significantly higher in cells cultured without serum in comparison to cells cultured with 2% FBS, and the levels in the cells with 2% PRP were reduced to 5 10% of those in the cells without serum. These results indicated that ccdPAs exhibit anti- apoptotic activities, in addition to increased proliferation, when cultured in 2% PRP in comparison to the same concentration of FBS, and that this was accompanied with reduced levels of DAPK1 and BIM mRNA expression in in vitro culture. PRP may improve the outcome of transplantation of adipose tissue by enhancing the anti-apoptotic activities of the implanted preadipocytes. PMID- 22314198 TI - Total and bone-specific alkaline phosphatases in haemodialysis patients with chronic liver disease. AB - OBJECTIVE: The Kidney Disease: Improving Global Outcomes "KDIGO" recommends regular sampling of bone turnover markers (BTMs) such as total alkaline phosphatases (t-ALP) and bone-specific alkaline phosphatase (b-ALP) in the case of haemodialysis (HD) patients. DESIGN AND METHODS: We present our results of the regular assessment of t-ALP, b-ALP, and PTH, obtained for existing HD patients with chronic liver disease (LD). RESULTS: 76 prevalent HD patients were examined. Linear regression showed that b-ALP and t-ALP levels were closely related (r2: 0.6; p<0.0001), even when the serum PTH level was <250 pg/mL (r2: 0.56; p<0.001). The b-ALP/t-ALP ratio was 0.07 +/- 0.12 and correlated poorly with PTH levels (r2: 0.03; p=0.01). Both b-ALP and t-ALP levels did not correlated with PTH levels. CONCLUSION: Our results did not confirm the KDIGO recommendation for using b-ALP as BTM in the special cases of HD patients with LDs. PMID- 22314200 TI - Cellular models to investigate biochemical pathways in Parkinson's disease. AB - Cellular models are instrumental in dissecting a complex pathological process into simpler molecular events. Parkinson's disease is multifactorial and clinically heterogeneous; the aetiology of the sporadic (and most common) form is still unclear and only a few molecular mechanisms have been clarified so far in the neurodegenerative cascade. In such a multifaceted picture, it is particularly important to identify experimental models that simplify the study of the different networks of proteins/genes involved. Cellular models that reproduce some of the features of the neurons that degenerate in Parkinson's disease have contributed to many advances in our comprehension of the pathogenic flow of the disease. In particular, the pivotal biochemical pathways (i.e. apoptosis and oxidative stress, mitochondrial impairment and dysfunctional mitophagy, unfolded protein stress and improper removal of misfolded proteins) have been widely explored in cell lines, challenged with toxic insults or genetically modified. The central role of alpha-synuclein has generated many models aiming to elucidate its contribution to the dysregulation of various cellular processes. In conclusion, classical cellular models appear to be the correct choice for preliminary studies on the molecular action of new drugs or potential toxins and for understanding the role of single genetic factors. Moreover, the availability of novel cellular systems, such as cybrids or induced pluripotent stem cells, offers the chance to exploit the advantages of an in vitro investigation, although mirroring more closely the cell population being affected. PMID- 22314199 TI - Air pollutant exposure and preterm and term small-for-gestational-age births in Detroit, Michigan: long-term trends and associations. AB - Studies in a number of countries have reported associations between exposure to ambient air pollutants and adverse birth outcomes, including low birth weight, preterm birth (PTB) and, less commonly, small for gestational age (SGA). Despite their growing number, the available studies have significant limitations, e.g., incomplete control of temporal trends in exposure, modest sample sizes, and a lack of information regarding individual risk factors such as smoking. No study has yet examined large numbers of susceptible individuals. We investigated the association between ambient air pollutant concentrations and term SGA and PTB outcomes among 164,905 singleton births in Detroit, Michigan occurring between 1990 and 2001. SO(2), CO, NO(2), O(3) and PM(10) exposures were used in single and multiple pollutant logistic regression models to estimate odds ratios (OR) for these outcomes, adjusted for the infant's sex and gestational age, the mother's race, age group, education level, smoking status and prenatal care, birth season, site of residence, and long-term exposure trends. Term SGA was associated with CO levels exceeding 0.75ppm (OR=1.14, 95% confidence interval=1.02-1.27) and NO(2) exceeding 6.8ppb (1.11, 1.03-1.21) exposures in the first month, and with PM(10) exceeding 35MUg/m(3) (1.22, 1.03-1.46) and O(3) (1.11, 1.02-1.20) exposure in the third trimester. PTB was associated with SO(2) (1.07, 1.01-1.14) exposure in the last month, and with (hourly) O(3) exceeding 92ppb (1.08, 1.02-1.14) exposure in the first month. Exposure to several air pollutants at modest concentrations was associated with adverse birth outcomes. This study, which included a large Black population, suggests the importance of the early period of pregnancy for associations between term SGA with CO and NO(2), and between O(3) with PTB; and the late pregnancy period for associations between term SGA and O(3) and PM(10), and between SO(2) with PTB. It also highlights the importance of accounting for individual risk factors such as maternal smoking, maternal race, and long-term trends in air pollutant levels and adverse birth outcomes in evaluating relationships between pollutant exposures and adverse birth outcomes. PMID- 22314201 TI - A novel approach for posterior chamber intraocular lens placement or rescue via a sutureless scleral fixation technique. PMID- 22314202 TI - A new magnetic resonance imaging scoring system for perilymphatic space appearance after intratympanic gadolinium injection, and its clinical application. AB - OBJECTIVE: To establish a new magnetic resonance imaging scoring system for diagnosing endolymphatic hydrops. PATIENTS AND METHODS: A total of 214 ears of 107 patients were categorised into five groups: no symptoms, Meniere's disease, sudden deafness, delayed endolymphatic hydrops and other ear disorders. Gadolinium distribution within the labyrinth was scored separately and quantitatively by two radiologists. Multiple independent-sample non-parametric tests, Bayesian discriminant analysis, multivariate logistic regression and receiver operating characteristic curve analyses were performed. RESULTS: The derived scoring model was highly accurate for diagnosing Meniere's disease and delayed endolymphatic hydrops. Two magnetic resonance imaging scoring methods for the perilymphatic space were proposed for the diagnosis of endolymphatic hydrops: a pre-1 value (a new variable that predicts individual probability) of more than 0.3982299, or a sum of all labyrinth component scores of less than 14.5. CONCLUSION: A convenient method is proposed which offers reliable radiological diagnostic criteria for Meniere's disease and delayed endolymphatic hydrops. PMID- 22314203 TI - Clustering of lifestyle factors in Spanish university students: the relationship between smoking, alcohol consumption, physical activity and diet quality. AB - OBJECTIVE: To ascertain the prevalence of and association between main lifestyle factors (diet, physical activity, alcohol consumption and smoking) in students from the Balearic Islands University. DESIGN: A cross-sectional, descriptive study. A questionnaire including questions on lifestyle, dietary habits and physical activity habits was administered to the students. Four different diet quality scores were calculated (Diet Diversity Score, Mediterranean Diet Score, Dietary Guidelines Score and Global Dietary Guidelines Score). SETTING: A sample of students from the Balearic Islands University. SUBJECTS: Nine hundred and eighty-seven students (45.5 % males; mean age 21.5 (sd 3.3) years). RESULTS: The dietary pattern of the student population was characterized by a low consumption of cereals and tubers, fruits, vegetables, olive oil, legumes and nuts, and a high consumption of processed meat, sweets, snacks, soft drinks and pastries. Linear, positive and statistically significant correlations were found between the number of meals consumed daily and all of the diet quality scores determined. Determinants of diet quality, both in the univariate and multivariate analyses, were physical activity practice, sex, age and number of meals consumed daily. CONCLUSIONS: Risk factors such as smoking, diet and physical inactivity had a tendency of clustering among Spanish university students. Overall diet quality was low, due to important departures from dietary recommendations and loss of the traditional Mediterranean dietary pattern. Nutritional education campaigns that include promotion of physical activity practice are needed to improve the overall health status of this population. PMID- 22314204 TI - Costs and benefits of rapid screening of methicillin-resistant Staphylococcus aureus carriage in intensive care units: a prospective multicenter study. AB - INTRODUCTION: Pre-emptive isolation of suspected methicillin-resistant Staphylococcus aureus (MRSA) carriers is a cornerstone of successful MRSA control policies. Implementation of such strategies is hampered when using conventional cultures with diagnostic delays of three to five days, as many non-carriers remain unnecessarily isolated. Rapid diagnostic testing (RDT) reduces the amount of unnecessary isolation days, but costs and benefits have not been accurately determined in intensive care units (ICUs). METHODS: Embedded in a multi-center hospital-wide study in 12 Dutch hospitals we quantified cost per isolation day avoided using RDT for MRSA, added to conventional cultures, in ICUs. BD GeneOhmTM MRSA PCR (IDI) and Xpert MRSA (GeneXpert) were subsequently used during 17 and 14 months, and their test characteristics were calculated with conventional culture results as reference. We calculated the number of pre-emptive isolation days avoided and incremental costs of adding RDT. RESULTS: A total of 163 patients at risk for MRSA carriage were screened and MRSA prevalence was 3.1% (n=5). Duration of isolation was 27.6 and 21.4 hours with IDI and GeneXpert, respectively, and would have been 96.0 hours when based on conventional cultures. The negative predictive value was 100% for both tests. Numbers of isolation days were reduced by 44.3% with PCR-based screening at the additional costs of ?327.84 (IDI) and ?252.14 (GeneXpert) per patient screened. Costs per isolation day avoided were ?136.04 (IDI) and ?121.76 (GeneXpert). CONCLUSIONS: In a low endemic setting for MRSA, RDT safely reduced the number of unnecessary isolation days on ICUs by 44%, at the costs of ?121.76 to ?136.04 per isolation day avoided. PMID- 22314205 TI - Response as an end point in treatment trials for acute GVHD. PMID- 22314206 TI - Human cerebral malaria and Plasmodium falciparum genotypes in Malawi. AB - BACKGROUND: Cerebral malaria, a severe form of Plasmodium falciparum infection, is an important cause of mortality in sub-Saharan African children. A Taqman 24 Single Nucleotide Polymorphisms (SNP) molecular barcode assay was developed for use in laboratory parasites which estimates genotype number and identifies the predominant genotype. METHODS: The 24 SNP assay was used to determine predominant genotypes in blood and tissues from autopsy and clinical patients with cerebral malaria. RESULTS: Single genotypes were shared between the peripheral blood, the brain, and other tissues of cerebral malaria patients, while malaria-infected patients who died of non-malarial causes had mixed genetic signatures in tissues examined. Children with retinopathy-positive cerebral malaria had significantly less complex infections than those without retinopathy (OR = 3.7, 95% CI [1.51 9.10]).The complexity of infections significantly decreased over the malaria season in retinopathy-positive patients compared to retinopathy-negative patients. CONCLUSIONS: Cerebral malaria patients harbour a single or small set of predominant parasites; patients with incidental parasitaemia sustain infections involving diverse genotypes. Limited diversity in the peripheral blood of cerebral malaria patients and correlation with tissues supports peripheral blood samples as appropriate for genome-wide association studies of parasite determinants of pathogenicity. PMID- 22314207 TI - Proliferation and plasticity of human beta cells on physiologically occurring laminin isoforms. AB - We have previously characterized the molecular composition of human islet basement membranes and shown that human beta cells bind to laminin 511 (LM511) through integrin alpha3beta1 and Lutheran glycoprotein. We have now investigated the impact of physical contact between cultured human beta cells and the laminin isoforms occurring in their natural niche. Human islet preparations derived from 15 donors were used, beta cells and duct cells were purified by magnetic sorting. Overall beta-cell proliferation was low or undetectable. However, in many experiments the only proliferating beta cells were detected in contact with the laminin isoforms that are found in the human islets in vivo (511 and 411). Purified ductal and beta cells underwent epithelial-mesenchymal transition (EMT). LM511 partially blocked this dedifferentiation of purified beta cells, and did not affect purified duct cells. Interactions with the surrounding basement membrane are important for the growth and function of human beta cells. However, only a very limited level of beta-cell proliferation can be induced by exogenous factors. LM511 may be a useful substrate for human beta-cell maintenance in vitro. PMID- 22314208 TI - Highly tunable charge transport in layer-by-layer assembled graphene transistors. AB - We demonstrate a controlled, systematic method to tune the charge transport in graphene field-effect transistors based on alternating layer-by-layer assembly of positively and negatively charged graphene oxide followed by thermal reduction. Surprisingly, tuning the number of bilayers of thermally reduced graphene oxide multilayer films allowed achieving either ambipolar or unipolar (both n- and p type) transport in graphene transistors. On the basis of X-ray photoemission spectroscopy, Raman spectroscopy, time-of-flight secondary ion mass spectrometry, and temperature-dependent charge transport measurements, we found that nitrogen atoms from the functional groups of positively charged graphene oxide are incorporated into the reduced graphene oxide films and substitute carbon atoms during the thermal reduction. This nitrogen-doping process occurs in different degrees for graphene multilayers with varying numbers of bilayers and thereby results in the interesting transition in the electrical behavior in graphene multilayer transistors. We believe that such a versatile method to control the charge transport in graphene multilayers will further promote their applications in solution-processable electronic devices based on graphene. PMID- 22314209 TI - Acquired amegakaryocytic thrombocytopenia in a patient with occupational chemical exposure. AB - Acquired amegakaryocytic thrombocytopenia (AAT) is a hematologic disorder that presents as thrombocytopenia with absent megakaryocytes in the bone marrow. Causes of AAT include toxins, drugs, viral infections, systemic lupus erythematosus, and cytokine deficiencies. Patients with AAT should be followed for possible progression to aplastic anemia or myelodysplastic syndrome. We present a case of a 61-year-old woman with AAT due to occupational chemical exposure. PMID- 22314210 TI - Evolving metformin treatment strategies in type-2 diabetes: from immediate release metformin monotherapy to extended-release combination therapy. AB - Over the last 40 years, metformin has revolutionized the treatment of type-2 diabetes worldwide and is still the most influential oral antidiabetic drug today. International guidelines now recommend that patients with type-2 diabetes are started on metformin therapy as soon as they are diagnosed, as it has been shown to improve long-term clinical outcomes compared with initial management with diet alone, without increasing the risk of developing hypoglycemia or weight gain. The older, immediate-release formulation of metformin does have some limitations, with incidence of gastrointestinal adverse effects restricting the dose in some patients, forming a barrier to treatment adherence, and subsequent glycemic control. However, the second-generation extended-release formulation (met XR) has the potential to overcome these challenges. In this review, we provide an overview of the evidence supporting the use of metformin as the first line gold standard for type-2 diabetes management and the expansion of its potential roles for the future. We also consider the advantages of met XR, in terms of its tolerability and convenient dose regimen, and review therapeutic options for when disease progression inevitably leads to inadequate control with monotherapy. These therapy options include the synergistic potential of combination strategies with met XR and dipeptidyl peptidase 4 inhibitors, a combination that has also been indicated for early-stage use (at diagnosis) as a potential method for preserving beta-cell function. PMID- 22314211 TI - Pathophysiology and management of acute kidney injury in the setting of abdominal compartment syndrome. AB - Abdominal compartment syndrome (ACS) is defined as an organ dysfunction caused by intra-abdominal hypertension (IAH). Up to 4.2% of the patients in intensive care unit may develop IAH with it being an independent predictor of mortality. However, overall, it still remains a relatively underdiagnosed condition, part in because physical examination alone is very unreliable. Acute kidney injury is one of the most consistently described organ dysfunctions with oliguria being one of the earliest clinical signs of IAH. We recommend that any patient with evidence of new onset oliguria in the setting of distended abdomen, unexplained respiratory failure, with or without hypotension should be suspected of having IAH/ACS. Intravesicular pressure measurement represents a safe, rapid, and cost effective method of diagnosing IAH. We hereby review the pathophysiology, diagnosis, and management of ACS and its association with acute kidney injury. PMID- 22314212 TI - Therapeutic case conference from Northwestern: an elderly gentleman with an unsteady gait. AB - We provide a Therapeutic Conference from Northwestern based on the case of a 63 year-old man who presented with cerebellar ataxia in the setting of a negative workup for a cerebrovascular event, toxic-metabolic, and infectious etiologies and was ultimately diagnosed with a paraneoplastic syndrome secondary to limited stage small cell lung cancer. A discussion of the clinical management including diagnostic workup and treatment of cerebellar ataxia paraneoplastic syndrome and limited-stage small cell lung cancer is provided. We also discuss the mechanisms of action of chemotherapy used to treat limited-stage small cell lung cancer and potential side effects associated with these agents. PMID- 22314213 TI - Maternal use of proton pump inhibitors during early pregnancy and the prevalence of hypospadias in male offspring. AB - Proton pump inhibitors (PPIs) are increasingly used in reflux disease treatment also among pregnant women. Hypospadias prevalence is increasing and the birth defect is diagnosed in 0.3%-0.8% of male births, but the association with maternal PPI use during pregnancy is virtually unknown. Therefore, we decided to estimate the hypospadias risk in male offspring after maternal PPI use during pregnancy. We used Danish nationwide registries to conduct a population-based prevalence study including all live-born boys from 1997 through 2009. Maternal PPI use was classified according to exposure time: early pregnancy (30 days before conception through the end of the first trimester) and entire pregnancy (30 days before and throughout pregnancy). Outcome was defined as a hospital hypospadias diagnosis recorded any time after delivery. We calculated prevalence ratios and 95% confidence intervals associating maternal PPI use with hypospadias in male offspring using Cox proportional hazard regression analysis and adjusted for confounding factors. We identified a total of 430,569 live-born boys of whom 2926 were exposed to maternal PPI use during early pregnancy. Among the exposed boys, 20 (0.7%) were diagnosed with hypospadias, whereas 2683 (0.6%) of the nonexposed had hypospadias (adjusted prevalence ratio = 1.1; 95% confidence interval, 0.7-1.7). A total of 5227 boys were exposed during the entire pregnancy, and 32 (0.6%) had hypospadias corresponding to a prevalence ratio of 1.0 (95% confidence interval, 0.7-1.4). The subanalysis restricted to omeprazole exposure showed similar results. We thus conclude that maternal PPI use during pregnancy was not associated with hypospadias in boy offspring. PMID- 22314214 TI - Community-based survey of amputation derived from the physically disabled person's certification in Kitakyushu City, Japan. AB - BACKGROUND: There were no recent reports of community-based surveys on the incidence, level and causes of amputation in Japan. OBJECTIVES: To identify any changes in the incidence, level, causes of amputation and gender distribution. STUDY DESIGN: A community-based survey. METHODS: The subjects were Kitakyushu citizens amputated between 2001 and 2005 and selected based on medical certificates for the physically disabled person's certificate. RESULTS: The incidence of amputation (/100,000 population per year) was 6.9 overall, 1.4 for upper limbs and 5.8 for lower limbs. The average age at amputation was 63.5 +/- 20.1 years and the male:female ratio was 1.9:1. The most frequent levels of amputations were partial hand amputation (84.4%) for upper limbs, and transtibial amputation (42.3%) and transfemoral amputation (36.8%) for lower limbs. The major causes were injuries (54.3%) for upper limbs, and peripheral vascular disorder (49.0%) and diabetes mellitus with peripheral circulatory complications (28.6%) for lower limbs. CONCLUSIONS: The incidence of amputation was 6.9 overall, 1.4 for upper limbs and 5.8 for lower limbs, and the male:female ratio was 1.9:1. In comparison to a previous survey the percentages of amputation due to peripheral circulatory disorders and injuries increased and decreased, respectively, and the rate of female amputations increased. CLINICAL RELEVANCE: This study provides useful data about change of the recent epidemiology of amputation in Kitakyushu, Japan. These data are essential to perform clinical practices in amputation rehabilitation, including prescription of prosthesis, general fatigue for aged amputees, and complication of peripheral circulatory disorders. PMID- 22314216 TI - Bibliography--editors' selection of current world literature. PMID- 22314215 TI - Caenorhabditis elegans Muscleblind homolog mbl-1 functions in neurons to regulate synapse formation. AB - BACKGROUND: The sequestration of Muscleblind splicing regulators results in myotonic dystrophy. Previous work on Muscleblind has largely focused on its roles in muscle development and maintenance due to the skeletal and cardiac muscle degeneration phenotype observed in individuals with the disorder. However, a number of reported nervous system defects suggest that Muscleblind proteins function in other tissues as well. RESULTS: We have identified a mutation in the Caenorhabditis elegans homolog of Muscleblind, mbl-1, that is required for proper formation of neuromuscular junction (NMJ) synapses. mbl-1 mutants exhibit selective loss of the most distal NMJ synapses in a C. elegans motorneuron, DA9, visualized using the vesicle-associated protein RAB-3, as well as the active zone proteins SYD-2/liprin-alpha and UNC-10/Rim. The proximal NMJs appear to have normal pre- and postsynaptic specializations. Surprisingly, expressing a mbl-1 transgene in the presynaptic neuron is sufficient to rescue the synaptic defect, while muscle expression has no effect. Consistent with this result, mbl-1 is also expressed in neurons. CONCLUSIONS: Based on these results, we conclude that in addition to its functions in muscle, the Muscleblind splice regulators also function in neurons to regulate synapse formation. PMID- 22314217 TI - Functional expression of Squalus acanthias melanocortin-5 receptor in CHO cells: ligand selectivity and interaction with MRAP. AB - The melanocortin-5 receptor (MC(5)) of the dogfish Squalus acanthias (SacMC(5) receptor) can be functionally expressed in CHO cells in the absence of the co expression of an exogenous MRAP cDNA. Both human ACTH(1-24) and dogfish ACTH(1 25) were much better stimulators of the SacMC(5) receptor than any of the mammalian or dogfish MSH ligands that were tested. The order of ligand selectivity for the dogfish melanocortins was ACTH(1-25)>alphaMSH>gamma-MSH=delta MSH>beta-MSH. Unlike mammalian MC(5) receptors, the functional expression of the SacMC(5) receptor was not negatively impacted when the receptor was co-expressed with a cartilaginous fish (Callorhinchus milii) MRAP2 cDNA. However, co expression with either mouse mMRAP1 or zebrafish zfMRAP1 increased the sensitivity of SacMC(5) receptor for hACTH(1-24) by at least one order of magnitude. Hence, SacMC(5) receptor has the potential to interact with MRAP1 orthologs and in this regard behaved more like a melanocortin MC(2) receptor ortholog than a melanocortin MC(5) receptor ortholog. These observations are discussed in light of the evolution of the melanocortin receptor gene family in cartilaginous fish, and the physiological implications of these observations are considered. PMID- 22314218 TI - Chrysin improves cognitive deficits and brain damage induced by chronic cerebral hypoperfusion in rats. AB - Chronic cerebral hypoperfusion, induced by permanent occlusion of bilateral common carotid arteries (2VO), is related to neurological disorders and contributes to cognitive decline. Chrysin (5,7-dihydroxyflavone) is an important member of the flavonoid family. The aim of this study is to investigate the effects of chrysin on cognitive deficits and brain damage in this rat 2VO model. At 52days after ligation, the escape latency in Morris water maze was significantly increased in rats subjected to 2VO, the neuronal damage was also increased accompanied by a large proliferation in glial fibrillary acidic protein (GFAP) immunoreactivity with marked white matter lesions, and neuronal cell apoptosis, all of which were significantly alleviated by long treatment of chrysin (30mg/kg). Biochemical examinations revealed that chrysin decreased lipid peroxide, reduced the increased activities of superoxide dismutase, and attenuated the decreased activities of glutathione peroxidase in 2VO rats. The results suggest that chrysin may have therapeutic potential for the treatment of neurodegeneration and dementia caused by decreased cerebral blood flow, which is most likely related, at least in part, to its anti-inflammatory and antioxidant properties. PMID- 22314219 TI - Effects of alpha1-adrenoceptor antagonists on phenylephrine-induced salivary secretion and intraurethral pressure elevation in anesthetized rats. AB - alpha(1)-Adrenoceptor antagonists are widely used for the treatment of voiding dysfunction associated with benign prostatic hyperplasia. Activation of alpha(1) adrenoceptors is reported to induce salivary secretion in rats and humans. However, the effects of alpha(1)-adrenoceptor antagonists on salivary secretion remain unknown. Here, we investigated the effects of the alpha(1)-adrenoceptor antagonists prazosin, silodosin, tamsulosin and urapidil on phenylephrine-induced salivary secretion and compared the results with the effects on phenylephrine induced intraurethral pressure (IUP) elevation in anesthetized rats. All antagonists inhibited phenylephrine-induced salivary secretion and IUP elevation in a dose-dependent fashion. Comparison of DR(10) values (the dose required to shift the dose-response curve 10-fold to the right) in both tissues showed that the inhibitory effect of silodosin was significantly more potent in the salivary gland than in the urethra (18-fold), but tamsulosin (2.3-fold), prazosin (1.7 fold) and urapidil (1.1-fold) did not show comparable tissue selectivity. These results suggest that alpha(1)-adrenoceptor antagonists inhibit not only urethral contraction but also salivary secretion, and that high tissue selectivity for the salivary gland over the urethra as shown by silodosin may contribute to the incidence of dry mouth. PMID- 22314220 TI - Emerging drug targets for pain treatment. AB - Pain is a global health challenge. For decades, we have been primarily relying upon opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) for pain management. However, adverse effects related to opioid and NSAID use are severe and often lead to forced drug discontinuation and inadequate pain relief. Despite decades of research, currently available pharmacotherapies for pain still fall short of clinical needs. Fortunately, with our increased understanding of the neurobiology and pathophysiology of pain, new drug targets have been emerging, which may lead to novel therapeutic strategies. This perspective will briefly review the theoretical development and experimental evidence of four emerging drug targets for pain treatment: transient receptor potential ankyrin (TRPA) 1 channel, cannabinoid CB(2) receptors, GABA(A) subtype receptors, and imidazoline I(2) receptors. Sustained efforts on these novel drug targets will increase the appreciation for these targets and expedite the development of lead compounds to reach clinical stage, which will undoubtedly strengthen our pharmacotherapeutic armaments against various debilitating painful conditions. PMID- 22314221 TI - Sesamin exerts renoprotective effects by enhancing NO bioactivity in renovascular hypertensive rats fed with high-fat-sucrose diet. AB - In the present study, we aimed to evaluate the protective effect of sesamin on kidney damage and renal endothelial dysfunction in two-kidney, one-clip renovascular hypertensive rats fed with a high-fat-sucrose diet (2K1C rats on HFS diet). Sesamin was intragastrically administered to 2K1C rats on HFS diet for eight weeks. Then, we measured the levels of serum hydrogen peroxide (H2O2), total antioxidant capability (T-AOC), renal malonaldehyde (MDA), total erythrocuprein (T-SOD) and glutathione peroxidase (GSH-P(X)). The expressions of endothelial nitric oxide synthase (eNOS), nitrotyrosine and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p47(phox) in the left and right renal cortexes were detected by Western blotting. Pathological changes in the left and right renal cortexes were observed by periodic acid-schiff staining (PAS) and Masson's staining. Treatment with sesamin (120 and 60mg/kg-1.d-1) in 2K1C rats on HFS diet improved renal function, corrected structural abnormalities, and attenuated renal oxidative stress. Furthermore, sesamin increased eNOS protein expression and reduced nitrotyrosine and p47phox protein expression. These results demonstrated that long-term treatment with sesamin had renoprotective effect and improved renal endothelial dysfunction via upregulation of eNOS expression and reduction of NO oxidative inactivation in both clipped and contralateral kidneys of 2K1C rats on HFS diet, and sesamin may have a favorably therapeutic value in treating chronic kidney disease in patients with hypertension and hyperlipemia. PMID- 22314222 TI - Involvement of perivascular nerves and transient receptor potential vanilloid 1 (TRPV1) in vascular responses to histamine in rat mesenteric resistance arteries. AB - A previous report showed that histamine in denuded mesenteric vascular beds produced a triphasic response; an initial small histamine H(2) receptor-mediated vasodilation, a transient histamine H(1) receptor-mediated vasoconstriction, and finally a long-lasting vasodilation. We further investigated the vascular effect of histamine in mesenteric preparations without an endothelium to clarify the possible involvement of perivascular nerves. Male Wistar rat mesenteric vascular beds without an endothelium were perfused with Krebs solution containing methoxamine to produce active tone and lafutidine to block histamine H(2) receptor-mediated vasodilation. Histamine (1-100MUM) was perfused for 1min and perfusion pressure was measured with a pressure transducer. Histamine caused a biphasic vascular response; initial vasoconstriction followed vasodilation. Tetrodotoxin (a neurotoxin, 1MUM) and procaine (a local anesthetic, 100MUM) significantly inhibited the vasoconstriction and vasodilation. Ruthenium red (a transient receptor potential vanilloid 1 (TRPV1) antagonist, 1MUM) also significantly inhibited both phases of the response. Pretreatment with capsaicin (a depletor of calcitonin gene-related peptide (CGRP)-containing nerves, 5MUM) significantly inhibited the vasodilation without affecting the initial vasoconstriction. Both indomethacin (a cyclooxygenase inhibitor, 0.5MUM) and seratrodast (a thromboxane A(2) receptor antagonist, 0.1MUM) abolished the histamine-induced vasoconstriction and subsequent vasodilation. These results suggest that histamine-induced vasoconstriction and long-lasting vasodilation are mediated by activation of TRPV1 on capsaicin-sensitive and capsaicin-insensitive nerves. They also suggest that perivascular nerves and prostanoids, probably thromboxane A(2), are responsible for the vascular response to histamine. PMID- 22314223 TI - Telmisartan inhibits vascular dysfunction and inflammation via activation of peroxisome proliferator-activated receptor-gamma in subtotal nephrectomized rat. AB - Telmisartan, an angiotensin II type 1 receptor blocker, reportedly exhibits a partial peroxisome proliferator-activated receptor (PPAR)-gamma agonistic action. To test whether telmisartan ameliorates vascular injury in the chronic kidney disease model rat through the PPAR-gamma pathway, telmisartan (5 mg/kg per day, orally), losartan (5 mg/kg per day, orally) or telmisartan plus PPAR-gamma antagonist, GW9662 (1 mg/kg/day, i.p.), was administered for 14 days to subtotal nephrectomized rats (Nx). There was no significant difference in systolic blood pressure or fasting blood glucose values among all groups. Subtotal nephrectomy significantly aggravated the levels of urinary protein excretion, blood urea nitrogen and plasma malondialdehyde concentration, which were attenuated by telmisartan or losartan treatment. Vasodilation in response to acetylcholine in the aortic ring was impaired in the Nx, and improved by treatment with telmisartan. Immunohistochemical analysis revealed that the infiltration of adventitial areas by macrophages and expression of osteopontin and vascular cell adhesion molecule-1 were enhanced in the Nx aorta and the overexpression was suppressed by telmisartan. The increased NADPH oxidase-derived superoxide production in the aorta from the Nx rat was suppressed by telmisartan. Cotreatment with GW9662 partly blunted the normalization of vascular dysfunction and inflammation. While losartan also attenuated these vascular changes in the Nx rats, the extent of the attenuation was significantly greater in the telmisartan treated group than in the losartan-treated group. These results suggest that, in addition to a class effect of angiotensin II type 1 receptor blockers, telmisartan exerted vasoprotective effects through its PPAR-gamma agonistic property in rats with renal failure. PMID- 22314224 TI - Ginsenoside Rh1 suppresses matrix metalloproteinase-1 expression through inhibition of activator protein-1 and mitogen-activated protein kinase signaling pathway in human hepatocellular carcinoma cells. AB - Invasion and metastasis are the major causes of treatment failure in patients with cancer. Here, we investigated the effects of ginsenoside Rh1 on tumor invasion and metastasis in human hepatocellular carcinoma HepG2 cells and its possible mechanism of action. Rh1 showed concentration- and time-dependent inhibition of HepG2 cell migration and invasion. Matrix metalloproteinase-1 (MMP 1) gene expression and its promoter activity were also concentration-dependently inhibited by Rh1 treatment. The inhibitory effect of Rh1 on MMP-1 expression was due to inactivation of the mitogen-activated protein kinases (MAPKs) ERK, JNK, and p38 MAPK. By transient transfection analysis with the MMP-1 promoter (-2846 to -29 nt) and AP-1 promoter, MMP-1 and AP-1 promoter activities were induced by phorbol myristate acetate (PMA) but were significantly inhibited by PD98059 (ERK1/2 inhibitor) or SP600125 (JNK inhibitor). The induction of MMP-1 and AP-1 promoters by PMA was attenuated by Rh1, and both promoter activities were synergistically inhibited by co-treatment with PD98059. To evaluate the effects of Rh1 on AP-1 dimers, expression analysis and electrophoretic mobility shift (EMSA) assay using radiolabeled AP-1-specific oligomers at proximal site (-73 nt) and distal site (-1600 nt) of the MMP-1 promoter were performed. The results showed that Rh1 inhibited the expression of c-Jun and c-Fos but did not affect the DNA binding ability of AP-1-specific oligomers. However, Rh1 attenuated the stability of c-Jun. Therefore, Rh1 has potential for development of novel chemotherapeutic agents for treatment of malignant cancers, including early hepatocellular carcinoma related to MMP-1 expression. PMID- 22314225 TI - R278995/CRA0450, a corticotropin-releasing factor (CRF(1)) receptor antagonist modulates REM sleep measures in rats: Implication for therapeutic indication. AB - Abnormalities in the regulation of the hypothalamic stress hormone corticotropin releasing factor (CRF) are thought to play a critical role in mood disorders. Consequently, CRF receptor antagonists have been proposed as potential novel therapeutic agents of these conditions. Sleep disturbance is common in depressed patients and changed sleep-wake architecture is considered as potential predictor or surrogate marker of response to treatment. The aim of our study was to characterise the effects of oral administration of the corticotropin-releasing factor CRF(1) receptor antagonist R278995/CRA0450 (3 and 10mg/kg) on sleep-wake organization and electroencephalographic (EEG) components in Sprague-Dawley rats, and to determine whether the changes observed in the sleep-EEG pattern resemble those seen with antidepressants. At 3mg/kg, R278995/CRA0450 produced minor changes in sleep behaviour, while an overall reduction in power spectra was observed during deep slow wave sleep. At 10mg/kg, R278995/CRA0450 consistently reduced rapid eye movement (REM) sleep (-75.4%) and increased the REM sleep onset latency (+67%, 92.1+/-4.9min for vehicle vs. 153.8+/-24min for R278995/CRA0450), in the absence of systematic changes in spectral EEG pattern, which are characteristic anti-depressant-like effects. These findings in rats indicate that the corticotropin-releasing factor CRF(1) receptor antagonist R278995/CRA0450 is centrally active under standard conditions as it inhibits REM sleep and promotes wakefulness. The characteristic changes found in the sleep EEG model further support the hypothesis that R278995/CRA0450 could exert a non-sedative, antidepressant-like action. PMID- 22314226 TI - Body dissatisfaction and socio-cultural factors in women with and without BED: their relation with eating psychopathology. AB - The goal of the present study was to assess the role of body dissatisfaction and socio-cultural factors on eating psychopathology in women with Binge Eating Disorder (BED) and women without BED. Seventy obese women consecutively evaluated participated: 35 with BED and 35 without BED who attended for the first time in a weight loss program. All participants completed a battery of questionnaires, including: Body Shape Questionnaire, Questionnaire of Influences on the Aesthetic Body Shape Model, Questionnaire on Eating and Weight Patterns, Three Factor Eating Questionnaire, and they were interviewed with the Interview for the Diagnosis of Eating Disorder-IV. The Body Mass Index, Waist-to-Hip Ratio and Body Fat were calculated. The results showed that 21% of obese women who participated in a weight reduction program met BED criteria. The scores of body dissatisfaction, influences of socio-cultural factors and eating psychopathology were higher in women with BED compared with women without BED. In the same way, significantly stronger correlations were found among influences of socio-cultural factors, specifically, influence of advertisement, social relations and eating psychopathology in women with BED than women without BED. It is concluded that the high body dissatisfaction as well as stronger associations among influence of socio-cultural factors and eating psychopathology could play an important role in women with BED. PMID- 22314227 TI - Stridor as a presentation of fourth branchial pouch sinus. AB - BACKGROUND: Anomalies of the fourth arch are the rarest of all the branchial anomalies. They arise as a result of failure of involution of the cleft during embryogenesis, and manifest clinically as sinuses, cysts or abscesses in the neck, commonly presenting in childhood. METHODS: This article describes a case of a neonate presenting with stridor which was secondary to a fourth branchial pouch sinus. The presentation, investigations, operative findings and treatment are discussed. RESULTS: Microlaryngobronchoscopy was done to evaluate the stridor. A swelling in the posterolateral pharyngeal wall and a sinus opening in the pyriform fossa on the left side were identified. There were no external neck swellings. Magnetic resonance imaging confirmed a swelling in the expected region filled with air and fluid. After the diagnosis was confirmed, the swelling was aspirated and the fourth arch pouch treated. Microlaryngobronchoscopy was repeated six weeks later, showing complete resolution of the pharyngeal swelling. At this stage, the child had no airway symptoms and was feeding normally. CONCLUSION: This is an interesting case of a fourth branchial cleft pouch presenting with stridor. The child was treated without any complications and recovered well. PMID- 22314228 TI - An epidemiological survey of children's iodine nutrition and goitre status in regions with mildly excessive iodine in drinking water in Hebei Province, China. AB - OBJECTIVE: To identify children's iodine nutrition and goitre status in areas with mildly excessive iodine in drinking water. DESIGN: A cross-sectional survey. Probability proportional to size sampling was employed to randomly select children from thirty townships where the median iodine content in drinking water ranged from 150 to 300 MUg/l; their urinary iodine concentrations were determined and their thyroid volumes were measured by ultrasound. Drinking water samples and salt samples from the villages where the children lived were collected using a systematic sampling method. SETTING: Hebei Province of China. SUBJECTS: A total of 1259 children aged 8-10 years (621 boys and 638 girls). RESULTS: Children's median urinary iodine concentration was found to be 418.8 MUg/l, and the iodine concentration was >300 MUg/l for 68.3 % (248/363) of the urine samples. Children's median urinary iodine concentration in villages with median salt iodine >10 mg/kg was significantly higher than that in villages with median salt iodine <5 mg/kg (442.9 MUg/l v. 305.4 MUg/l, P ~ 0). The goitre rate of 1259 children examined by ultrasound was 10.96 %. CONCLUSIONS: The iodine intake of children living in areas with mildly excessive iodine in drinking water in Hebei Province was found to be excessive. The measured iodine excess in the sampled children is exacerbated by consumption of iodized salt. Goitre was identified in these areas; however, due to the limitation of the current criteria for children's thyroid volume, a comprehensive assessment of the prevalence of goitre in these regions could not be made and further study is required. PMID- 22314229 TI - Evaluation of Streptomyces coelicolor A3(2) as a heterologous expression host for the cyanobacterial protein kinase C activator lyngbyatoxin A. AB - Filamentous marine cyanobacteria are extremely rich sources of bioactive natural products and often employ highly unusual biosynthetic enzymes in their assembly. However, the current lack of techniques for stable DNA transfer into these filamentous organisms, combined with the absence of heterologous expression strategies for nonribosomal cyanobacterial gene clusters, prohibit the creation of mutant strains or the heterologous production of these cyanobacterial compounds in other bacteria. In this study, we evaluated the capability of a derivative of the model actinomycete Streptomyces coelicolor A3(2) to express enzymes involved in the biosynthesis of the protein kinase C activator lyngbyatoxin A from a Hawaiian strain of Moorea producta (previously classified as Lyngbya majuscula). Despite large differences in GC content between these two bacteria and the presence of rare TTA/UUA leucine codons in lyngbyatoxin ORFs we were able to achieve expression of the cytochrome P450 monooxygenase LtxB and reverse prenyltransferase LtxC in S. coelicolor M512 and confirmed the in vitro functionality of S. coelicolor overexpressed LtxC. Attempts to express the entire lyngbyatoxin A gene cluster in S. coelicolor M512 were not successful because of transcript termination observed for the ltxA gene, which encodes a large nonribosomal peptide synthetase. However, these attempts did show a detectable level of cyanobacterial promoter recognition in Streptomyces. Successful expression of lyngbyatoxin A proteins in Streptomyces provides a new platform for biochemical investigation of natural product enzymes from Moorea strains. PMID- 22314230 TI - Skullcapflavone II inhibits ovalbumin-induced airway inflammation in a mouse model of asthma. AB - Skullcapflavone II is a flavonoid derived from Scutellaria baicalensis, a widely used herbal medicine in anti-inflammatory and anticancer therapy in Korea. Skullcapflavone II antagonized the bradykinin receptor more potently than any of the other flavonoids derived from this plant. Here, we were investigated its therapeutic effects in a mouse model of ovalbumin (OVA)-induced allergic asthma. Administration of skullcapflavone II significantly reduced airway hyperresponsiveness (AHR), airway eosinophilia, Th2 cytokine production, and increased transforming growth factor-beta1 (TGF-beta1) levels in bronchoalveolarlavage (BAL) fluids and lungs from OVA-sensitized and -challenged mice. Skullcapflavone II administration also significantly suppressed subepithelial collagen deposition and goblet cell hyperplasia, elevated Smad7 expression and suppressed pSmad2/3 levels. Collectively, these findings indicate that skullcapflavone II, a potential bradykinin antagonist, reduced the major pathophysiological features of allergic asthma, at least in part by acting on TGF beta1/Smad signaling pathways. Thus, skullcapflavone II may have therapeutic potential for the treatment of allergic asthma. PMID- 22314231 TI - Incidence of hepatocellular carcinoma and response to interferon therapy in HCV infected patients: effect of factors associated with the therapeutic response and incidence of HCC. PMID- 22314232 TI - Palmitoylated calnexin is a key component of the ribosome-translocon complex. AB - A third of the human genome encodes N-glycosylated proteins. These are co translationally translocated into the lumen/membrane of the endoplasmic reticulum (ER) where they fold and assemble before they are transported to their final destination. Here, we show that calnexin, a major ER chaperone involved in glycoprotein folding is palmitoylated and that this modification is mediated by the ER palmitoyltransferase DHHC6. This modification leads to the preferential localization of calnexin to the perinuclear rough ER, at the expense of ER tubules. Moreover, palmitoylation mediates the association of calnexin with the ribosome-translocon complex (RTC) leading to the formation of a supercomplex that recruits the actin cytoskeleton, leading to further stabilization of the assembly. When formation of the calnexin-RTC supercomplex was affected by DHHC6 silencing, mutation of calnexin palmitoylation sites or actin depolymerization, folding of glycoproteins was impaired. Our findings thus show that calnexin is a stable component of the RTC in a manner that is exquisitely dependent on its palmitoylation status. This association is essential for the chaperone to capture its client proteins as they emerge from the translocon, acquire their N-linked glycans and initiate folding. PMID- 22314233 TI - Structure and assembly of the SF3a splicing factor complex of U2 snRNP. AB - SF3a is an evolutionarily conserved heterotrimeric complex essential for pre-mRNA splicing. It functions in spliceosome assembly within the mature U2 snRNP (small nuclear ribonucleoprotein particle), and its displacement from the spliceosome initiates the first step of the splicing reaction. We have identified a core domain of the yeast SF3a complex required for complex assembly and determined its crystal structure. The structure shows a bifurcated assembly of three subunits, Prp9, Prp11 and Prp21, with Prp9 interacting with Prp21 via a bidentate-binding mode, and Prp21 wrapping around Prp11. Structure-guided biochemical analysis also shows that Prp9 harbours a major binding site for stem-loop IIa of U2 snRNA. These findings provide mechanistic insights into the assembly of U2 snRNP. PMID- 22314234 TI - Architecture and nucleic acids recognition mechanism of the THO complex, an mRNP assembly factor. AB - The THO complex is a key factor in co-transcriptional formation of export competent messenger ribonucleoprotein particles, yet its structure and mechanism of chromatin recruitment remain unknown. In yeast, this complex has been described as a heterotetramer (Tho2, Hpr1, Mft1, and Thp2) that interacts with Tex1 and mRNA export factors Sub2 and Yra1 to form the TRanscription EXport (TREX) complex. In this study, we purified yeast THO and found Tex1 to be part of its core. We determined the three-dimensional structures of five-subunit THO complex by electron microscopy and located the positions of Tex1, Hpr1, and Tho2 C-terminus using various labelling techniques. In the case of Tex1, a beta propeller protein, we have generated an atomic model which docks into the corresponding part of the THO complex envelope. Furthermore, we show that THO directly interacts with nucleic acids through the unfolded C-terminal region of Tho2, whose removal reduces THO recruitment to active chromatin leading to mRNA biogenesis defects. In summary, this study describes the THO architecture, the structural basis for its chromatin targeting, and highlights the importance of unfolded regions of eukaryotic proteins. PMID- 22314235 TI - MDA5 cooperatively forms dimers and ATP-sensitive filaments upon binding double stranded RNA. AB - Melanoma differentiation-associated gene-5 (MDA5) detects viral double-stranded RNA in the cytoplasm. RNA binding induces MDA5 to activate the signalling adaptor MAVS through interactions between the caspase recruitment domains (CARDs) of the two proteins. The molecular mechanism of MDA5 signalling is not well understood. Here, we show that MDA5 cooperatively binds short RNA ligands as a dimer with a 16-18-basepair footprint. A crystal structure of the MDA5 helicase-insert domain demonstrates an evolutionary relationship with the archaeal Hef helicases. In X ray solution structures, the CARDs in unliganded MDA5 are flexible, and RNA binds on one side of an asymmetric MDA5 dimer, bridging the two subunits. On longer RNA, full-length and CARD-deleted MDA5 constructs assemble into ATP-sensitive filaments. We propose a signalling model in which the CARDs on MDA5-RNA filaments nucleate the assembly of MAVS filaments with the same polymeric geometry. PMID- 22314236 TI - The caudal bursa in the Heligmonellidae (Nematoda: Trichostrongylina). Characterization and hypothesis on its evolution. AB - The different patterns of the caudal bursa of the Heligmonellidae (Nematoda) are redefined, taking into account the grouping of rays 2-6 and the sequence of origin of these rays from their common trunk. The type of symmetry of the caudal bursa is also redefined. The following patterns were observed and characterized: the basic patterns: types 2-3, 2-2-1, 1-3-1 and 1-4 and the intermediary patterns: type 2-3 tending to type 2-2-1, type 2-2-1 tending to type 1-3-1, type 1-3-1 tending to type 1-4 and type 2-2-1 tending to type 1-4. An evolutionary interpretation of the patterns is attempted and seems to follow the direction: 2 3 to 2-2-1 to 1-3-1 to 1-4. Seven atypical patterns are described. The caudal bursae were classified based on their symmetry: subsymmetrical, dissymmetrical and asymmetrical. Independently of the type of symmetry, the two latero-ventral lobes may have the same or different patterns. The type of symmetry, the ratio between the two latero-ventral lobes and a characteristic pattern were utilized to characterize the caudal bursae at the level of the genus and the subfamily. The combination of the right/left ratio and the type of symmetry gives heterogeneous results, with no real association between these characters. The most conspicuous asymmetries and dissymmetries were found among the Nippostrongylinae. The most frequent pattern in the Heligmonellidae is the basic type 2-2-1; types 1-3-1 and 1-4 are less frequent but are characteristic of several genera; type 1-4 is absent from the Heligmonellinae. Whatever the pattern, in the Heligmonellidae rays 4 and 5 are the last to diverge from the common trunk of rays 2-6. PMID- 22314237 TI - Development of Trichosomoides nasalis (Nematoda: Trichinelloidea) in the murid host: evidence for larval growth in striated muscle fibres. AB - Trichosomoides nasalis (Trichinelloidea) is a parasite of Arvicanthis niloticus (Muridae) in Senegal. Female worms that harbour dwarf males in their uteri, occur in the epithelium of the nasal mucosa. Young laboratory-bred A. niloticus were either fed females containing larvated eggs or intraperitoneally injected with motile first-stage larvae recovered from female uteri. Both resulted in successful infection. Organs examined during rodent necropsy were blood and lymphatic circulatory systems (heart, large vessels, lymphnodes), lungs, liver, kidneys, thoracic and abdominal cavities, thoracic and abdominal muscular walls, diaphragm, tongue, and nasal mucosa. Development to adult nasal stages took three weeks. Recovery of newly hatched larvae from the peritoneal fluid at four-eight hours after oral infection suggests a direct passage from the stomach or intestinal wall to the musculature. However, dissemination through the blood, as observed with Trichinella spiralis, cannot be excluded even though newly hatched larvae of T. nasalis are twice as thick (15 MUm). Developing larvae were found in histological sections of the striated muscle of the abdominal and thoracic walls, and larvae in fourth moult were dissected from these sites. Adult females were found in the deep nasal mucosa where mating occurred prior to worms settling in the nasal epithelium. The present study shows a remarkable similarity between T. nasalis and Trichinella species regarding muscle tropism, but the development of T. nasalis is not arrested at the late first-larval stage and does not induce transformation of infected fibres into nurse cells. T. nasalis seems a potential model to study molecular relations between trichinelloid larvae and infected muscle fibres. PMID- 22314238 TI - [Description of Nosopsyllus (N.) atsbi n. sp. (Siphonaptera: Ceratophyllidae) from Ethiopia, and revision of the related species N. (N.) incisus (Jordan & Rothschild, 1913); biogeographical discussion]. AB - We describe a new Nosopsyllus s. sto., N. atsbi, from the north of Ethiopia, that shows phyletic similarities with N. incisus (Jordan & Rothschild, 1913), a species from the oriental part of the afrotropical region. This led us to reconsider the classification of the incisus populations based on the unique criteria of telomere's setation (three robust marginal bristles, instead of the two typically present in members of this genus and subgenus). It appears that N. incisus s. sto. occurs in north-eastern Democratic Republic of the Congo, Kenya, Burundi and Tanzania. In the north and south of this region (respectively central Ethiopia, on one hand, Zambia and Malawi, on the other hand), two taxa are morphologically distinct and we erect them here to the rank of subspecies: Nosopsyllus (N.) incisus traubi n. ssp. and N. (N.) incisus lewisi n. ssp. Actually, four taxa are in "incisus complex", namely: N. atsbi n. sp., N. incisus traubi n. ssp., N. incisus incisus (Jordan & Rothschild, 1913), and N. incisus lewisi n. ssp. PMID- 22314239 TI - [Revision of of the subfamily of Metaracoelophryinae de Puytorac 1972 (Oligohymenophora: Hoplytophryida: Hoplytophryidae), astome ciliates of the digestive tract of Oligochaeta worms of Africa: description of five new species]. AB - Five new species belonging to the astome ciliates, living in the digestive tract of Oligochaeta worms belonging to the genus Alma from Cameroon, have been described. The techniques used are: vital staining, staining of the nucleus with Diamidino Phenyl Indol (DAPI), scanning electron microscopy and silver staining method (Fernandez Galiano, 1976, 1994). This work confirms the presence of the genus Paracoelophrya and Dicoelophrya in the digestive track of the oligochaete Alma from Gabon and Cameroon; it helps to understand the general taxonomy of this Metaracoelophryinae subfamily. Moreover, the homogeneity of this group is confirmed and the phylogenetic relationship inside the Hoplitophryida order need more studies to be solved. PMID- 22314240 TI - Contrasting views of animal healthcare providers on worm control practices for sheep and goats in an arid environment. AB - A questionnaire survey was conducted to determine the worm control practices and anthelmintic usage of 150 key respondents involved in sheep and goat production in the arid Thal area of Pakistan. The information was collected by visiting farms, and interviewing the key respondents which included veterinary officers (n = 15), veterinary assistants (n = 51), traditional practitioners (n = 24), and small and large scale sheep/goat farm herders and owners (n = 60). Among all interviewed animal healthcare providers, the veterinary officers had the highest level of awareness of parasitic infection and advocated the use of modern available anthelmintics according to the predefined schedule. The farmers on the other hand, had the lowest level of knowledge about parasitic infections. They used modern anthelmintics at low frequencies (every six months) following an unusual practice of diluting the medicine. Veterinary assistants had a medium level of awareness about the parasitic infections using anthelmintic treatments when they deemed necessary rather than following a predefined treatment schedule. Traditional practitioners were also aware of parasitic infections and used traditional anthelmintics or a combination of the traditional and modern anthelmintics. The animal health providers had a different awareness and knowledge of parasitic infections which resulted in contrasting proposals for its' control. The farmers used worm control measures in accordance with their own views and those of animal healthcare advisors, combining modern and traditional treatments. This study provides the first insight into the differing views of those animal healthcare providers who form the basis for effective parasitic control within the sheep and goat industry of an arid region. PMID- 22314241 TI - In silico analysis of a therapeutic target in Leishmania infantum: the guanosine diphospho-D-mannose pyrophosphorylase. AB - Leishmaniases are tropical and sub-tropical diseases for which classical drugs (i.e. antimonials) exhibit toxicity and drug resistance. Such a situation requires to find new chemical series with antileishmanial activity. This work consists in analyzing the structure of a validated target in Leishmania: the GDP mannose pyrophosphorylase (GDP-MP), an enzyme involved in glycosylation and essential for amastigote survival. By comparing both human and L. infantum GDP-MP 3D homology models, we identified (i) a common motif of amino acids that binds to the mannose moiety of the substrate and, interestingly, (ii) a motif that is specific to the catalytic site of the parasite enzyme. This motif could then be used to design compounds that specifically inhibit the leishmanial GDP-MP, without any effect on the human homolog. PMID- 22314242 TI - Prevalence of Cryptosporidium-like infection in one-humped camels (Camelus dromedarius) of northwestern Iran. AB - Cryptosporidium is a ubiquitous enteropathogen protozoan infection affecting livestock worldwide. The present study was carried out to determine the prevalence of Cryptosporidium infection in different age groups of dromedary camels in northwestern Iran from November 2009 to July 2010. A total number of 170 fecal samples were collected and examined using modified Ziehl-Neelsen (MZN) staining under light microscope. Examination of stained fecal smears revealed that 17 camels (10%) were positive for Cryptosporidium-like. The prevalence of Cryptosporidium-like was significantly higher in camel calves (< 1 years old) (20%) than other age groups, in which the diarrhoeic calves had the prevalence of 16%. In adult camels the prevalence was 6.5%. There was no significant difference in the prevalence of Cryptosporidium-like between male and female camels. It is concluded that Cryptosporidium infection is a problem in camel husbandry and could be of public health concern in the region. PMID- 22314243 TI - [A case of feline leishmaniasis in the south of France]. AB - We report a case of disseminated feline leishmaniasis in a FIV-seropositive 14 year-old male cat (Felis catus) living in the Alpes-Maritimes (south of France). The cat presented with erythematous ulcerated papules on the head and withers, and with an ulcerated proliferative lesion on the left pinnae. The condition was diagnosed, along with a squamous cell carcinoma of the pinnae, after histopathological examination of the cutaneous lesions. Total remission of the cutaneous lesions was obtained after oral administration of 100 mg of allopurinol once a day for four months. Necropsic samples revealed that the parasite was still present in the organism after six months of treatment. This case discusses of the cat sensibility to the leishmaniasis pathology and of his potential ability of being a reservoir host. PMID- 22314244 TI - Identification of the causative agent of cutaneous leishmaniasis in Chichaoua province, Morocco. AB - Cutaneous leishmaniasis (CL) in Morocco is caused by three species, Leishmania major, L. tropica and L. infantum. CL has been known in Chichaoua province since 2000. Using DNA extracted from microscopic slides and parasite cultures, collected in the years 2006 and 2009, we identified for the first time L. tropica as the causative agent of CL in this region. Species identification was achieved by performing the ITS1-PCR-RFLP approach. By using this method it was possible to identify parasites in Giemsa stained slides containing less than five parasites per oil-immersion field even they were conserved for up to four months. PMID- 22314245 TI - Molecular identification of Fasciola spp. (Digenea: Platyhelminthes) in cattle from Vietnam. AB - Fasciola spp. were collected from naturally infected cattle at a local abattoir of Khanh Hoa province, Vietnam, for morphological and genetic investigations. Microscopic examination detected no sperm cells in the seminal vesicles, suggesting a parthenogenetic reproduction of the flukes. Analyses of sequences from the first and second internal transcribed spacers (ITS1 and ITS2) of the ribosomal RNA revealed that 13 out of 16 isolates were of Fasciola gigantica type, whereas three isolates presented a hybrid sequence from F. gigantica and Fasciola hepatica. Interestingly, all the mitochondrial sequences (partial COI and NDI) were of F. gigantica type, suggesting that the maternal lineage of the hybrid form is from F. gigantica. No intra-sequence variation was detected. PMID- 22314246 TI - A comparison of two different techniques for the detection of blood parasite, Theileria annulata, in cattle from two districts in Khyber Pukhtoon Khwa Province (Pakistan). AB - The present study was carried out to determine the prevalence of Theileria annulata in large ruminants from two districts, Peshawar and Kohat, in Khyber Pukhtoon Khwa (Pakistan). Blood samples were collected from 95 cattle. Data on the characteristics of animals and herds were collected through questionnaires. No significant risk factors were found associated with the spread of tropical theileriosis in the study area. Two different parasite detection techniques, PCR amplification and screening of Giemsa stained slides, were compared and it was found that PCR amplification is a more sensitive tool (33.7% parasite detection), as compared to smear scanning (5.2% parasite detection) for the detection of Theileria annulata. 32 out of 95 animals, from both districts, produced the 721 bp fragment specific for Theileria annulata. PMID- 22314247 TI - The impact of dementia severity on caregiver burden in frontotemporal dementia and Alzheimer disease. AB - Caregiver burden is greater in frontotemporal dementia (FTD) than in Alzheimer disease (AD). However, little is known of the impact of the 3 main clinical variants of FTD- behavioral-variant frontotemporal dementia (bvFTD), semantic dementia (SemDem), and progressive nonfluent aphasia (PNFA)-or the role of disease severity in caregiver burden. The Zarit Burden Inventory was used to measure caregiver burden of bvFTD (n=17), SemDem (n=20), PNFA (n=20), and AD (n=19) patients. Symptom duration, caregiver age, and relationship type were matched across groups. Moreover, a number of caregiver (mood, social network) and patient variables (functional disability, behavioral changes, relationship with caregiver, and dementia stage) were addressed to investigate their impact on caregiver burden. Caregivers of bvFTD patients reported the highest burden, whereas SemDem and PNFA caregivers reported burden similar to AD. A regression analysis revealed that caregiver burden in FTD, regardless of subtype, was explained by a model combining disease staging, relationship changes, and caregiver depression. Burden increased with disease severity in FTD. This study is the first to show that caregivers of SemDem, PNFA, and AD patients show similar burden, while confirming that bvFTD caregivers show higher burden than AD caregivers. More importantly, this study demonstrates that burden worsens with disease progression in FTD. PMID- 22314248 TI - Predicting the risk of dementia among Canadian seniors: a useable practice friendly diagnostic algorithm. AB - Research has not provided feasible models to identify dementia in primary care. We construct a broadly based diagnostic algorithm synthesizing information from known risk factors, such as poor cognition, sociodemographic factors, and health history. Data were from the Canadian Study of Health and Aging (CSHA) Phase I. Dementia was diagnosed by clinical consensus. All subjects had a Mini-Mental State Examination (MMSE) score and a Modified MMSE (3MS) score. Multiple logistic regression was used to build our diagnostic algorithm, which was then tested for classification accuracy on the basis of the area under the receiver operating characteristic curve. The area under receiver operating characteristic curve for our diagnostic algorithm using 3MS as a binary variable was significantly greater than the 3MS alone (P<0.001). However, no significant difference was found when using 3MS as a continuous variable in the algorithm. Similarly, a binary MMSE algorithm would provide greater accuracy than MMSE alone. In terms of the usage of our algorithm in practice settings, given the prevalence of dementia, the clear benefits of accurate identification and earlier intervention, adding a few questions to the binary 3MS in our algorithm quantitatively improves the dementia prediction, which is important for patients, caregivers, and health providers. PMID- 22314249 TI - Ginsenoside Re: Its chemistry, metabolism and pharmacokinetics. AB - Ginsenosides, the bioactive components of ginseng, can be divided into two major groups, namely 20(S)-protopanaxatriol (e.g. Re, Rg1, Rg2, and Rb3) and 20(S) protopanaxadiol (e.g. Rb1, Rb2, Rc, and Rd). Biological and environmental factors may affect the content of ginsenosides in different parts of ginseng plant. Evidence from pharmacokinetic and metabolic studies of Re demonstrated that (1) the absorption of Re is fast in gastrointestinal tract; (2) Re may be metabolized mainly to Rh1 and F1 by intestinal microflora before absorption into blood; and (3) Re is quickly cleared from the body. PMID- 22314250 TI - Influence of age-related macular degeneration on macular thickness measurement made with fourier-domain optical coherence tomography. AB - PURPOSE: To evaluate the influence of age-related macular degeneration (AMD) on macular thickness measurement made with Fourier-domain optical coherence tomography (RTVue-OCT) to detect glaucoma. METHODS: : One nonglaucomatous eye of 79 white persons was imaged. This comprised 25 healthy eyes, 19 eyes with early/intermediate AMD (geographic atrophy excluded), 16 eyes with subfoveal choroidal neovascularization (CNV), and 19 CNV eyes after intravitreal antiangiogenic treatment [CNV-antivascular endothelial growth factor (VEGF)]. RESULTS: Compared with the age-matched controls, no difference in any nerve fiber layer and optic disc parameter was seen for any AMD group. No macular retinal segmentation error was detected in the control group. Localized inner retinal image segmentation errors topographically related to AMD were detected in 8 eyes with drusen (42.1%), all 16 CNV eyes (100%) and 17 eyes in the CNV-anti-VEGF group (89.5%; chi test, P<0.001 for all comparisons). The average macular thickness parameters did not differ between the control and the AMD groups (analysis of variance, P>0.05). In contrast, all pattern-based ganglion cell complex (GCC) parameters were significantly higher (more abnormal) in the CNV and CNV-anti-VEGF group than in the control eyes (Mann-Whitney test, Bonferroni correction, P<0.001). For GCC focal loss volume, the only pattern-based parameter classified by the software, the frequency of "borderline" and "outside normal limits" classifications was significantly greater in each AMD group than in the control group (chi test, Bonferroni correction, P <=0.03). CONCLUSIONS: In nonglaucomatous eyes, AMD significantly influences the pattern-based inner macular thickness parameters of the RTVue optical coherence tomograph and the software-provided classification of GCC focal loss volume, for detection of glaucoma. PMID- 22314251 TI - Progression of visual field defects in eyes with different optic disc appearances in patients with normal tension glaucoma. AB - PURPOSE: To investigate the relationship between the optic disc appearance and the progression of visual field defects in eyes with normal tension glaucoma (NTG). METHODS: Two hundred nine patients with NTG, who were being treated with topical antiglaucoma drugs and had been followed for at least 3 years, were studied. The baseline optic disc appearance was classified into 4 types: focal ischemic (FI), myopic glaucomatous (MY), senile sclerotic (SS), and generalized cup enlargement (GE). The progression of the NTG was assessed by the slope of the mean deviations (MDs) obtained from the visual field results collected during the follow-up examinations. The baseline and mean intraocular pressures (IOPs) were also followed. RESULTS: Twenty-seven patients were placed in the FI group, 63 into the MY group, 24 into the SS group, and 43 into the GE group. Fifty-two patients (24.9%) could not be classified. There were no significant differences in the percentage reduction of the IOP among the 4 groups. The MD slope in the GE group (-0.51+/-0.74 dB/y) was significantly steeper than that in the other groups. Regression analyses showed that the factors most associated with the MD slope were the age in the FI (r, -0.495) and the GE (r=0.496) groups, and the relative reduction of the IOP (r=0.413) in the SS group. None of the factors in the MY group was significantly associated with the MD slope. CONCLUSIONS: The rate of progression of the field defects, the MD slope, in patients with NTG is possibly dependent on the baseline optic disc appearance. Thus, the optic disc appearance may be useful for the management of patients with NTG. PMID- 22314252 TI - Charge-selective surface-enhanced Raman scattering using silver and gold nanoparticles deposited on silicon-carbon core-shell nanowires. AB - The deposition of silver (Ag) or gold (Au) nanoparticles (NPs) on vertically aligned silicon-carbon (Si-C) core-shell nanowires (NWs) produces sensitive substrates for surface-enhanced Raman spectroscopy (SERS). The undoped and 30% nitrogen (N)-doped graphitic layers of the C shell (avg thickness of 20 nm) induce a higher sensitivity toward negatively (-) and positively (+) charged dye molecules, respectively, showing remarkable charge selectivity. The Ag NPs exhibit higher charge selectivity than the Au NPs. The Ag NPs deposited on p- and n-type Si NWs also exhibit (-) and (+) charge selectivity, respectively, which is higher than that of the Au NPs. The X-ray photoelectron spectroscopy analysis indicates that the N-doped graphitic layers donate more electrons to the metal NPs than the undoped ones. More distinct electron transfer occurs to the Ag NPs than to the Au NPs. First principles calculations of the graphene-metal adducts suggest that the large electron transfer capacity of the N-doped graphitic layers is due to the formation of a N->Ag coordinate bond involving the lone pair electrons of the N atoms. We propose that the more (-) charged NPs on the N-doped graphitic layers prefer the adsorption of (+) charged dyes, enhancing the SERS intensity. The charge selectivity of the Si NW substrates can also be rationalized by the greater electron transfer from the n-type Si to the metal NPs. PMID- 22314253 TI - Educational inequalities in disability pensioning - the impact of illness and occupational, psychosocial, and behavioural factors: The Nord-Trondelag Health Study (HUNT). AB - AIMS: Socioeconomic inequalities in disability pensioning are well established, but we know little about the causes. The main aim of this study was to disentangle educational inequalities in disability pensioning in Norwegian women and men. METHODS: The baseline data consisted of 32,948 participants in the Norwegian Nord-Trondelag Health Study (1995-97), 25-66 years old, without disability pension, and in paid work. Additional analyses were made for housewives and unemployed/laid-off persons. Information on the occurrence of disability pension was obtained from the National Insurance Administration database up to 2008. Data analyses were performed using Cox regression. RESULTS: We found considerable educational inequalities in disability pensioning, and the incidence proportion by 2008 was higher in women (25-49 years 11%, 50-66 years 30%) than men (25-49 years 6%, 50-66 years 24%). Long-standing limiting illness and occupational, psychosocial, and behavioural factors were not sufficient to explain the educational inequalities: young men with primary education had a hazard ratio of 3.1 (95% CI 2.3-4.3) compared to young men with tertiary education. The corresponding numbers for young women were 2.7 (2.1-3.1). We found small educational inequalities in the oldest women in paid work and no inequalities in the oldest unemployed/laid-off women and housewives. CONCLUSIONS: Illness and occupational, psychosocial, and behavioural factors explained some of the educational inequalities in disability pensioning. However, considerable inequalities remain after accounting for these factors. The higher incidence of disability pensioning in women than men and the small or non-existing educational inequalities in the oldest women calls for a gender perspective in future research. PMID- 22314254 TI - Prion-induced toxicity in PrP transgenic Drosophila. AB - Prion diseases are fatal transmissible neurodegenerative diseases of humans and various vertebrate species. In their natural hosts these conditions are characterised by prolonged incubation times prior to the onset of clinical signs of terminal disease. Accordingly, tractable models of mammalian prion disease are required in order to better understand the mechanisms of prion replication and prion-induced neurotoxicity. Transmission of prion diseases can occur across a species barrier and this is facilitated in recipients transgenic for the same PrP gene as the individual from which the infectious prions are derived. Here we have tested the hypothesis that exogenous ovine prions can induce neurotoxicity in Drosophila melanogaster transgenic for ovine PrP. Drosophila that expressed ovine PrP pan neuronally and inoculated with ovine prions at the larval stage by oral exposure to scrapie-infected sheep brain homogenate showed markedly accelerated locomotor and survival defects. ARQ PrP transgenic Drosophila exposed to scrapie infected brain homogenate showed a significant and progressive reduction in locomotor activity compared to similar flies exposed to normal sheep brain homogenate. The prion-induced locomotor defect was accompanied by the accumulation of potentially misfolded PrP in the brains of prion-inoculated flies. VRQ PrP transgenic Drosophila, which expressed less ovine PrP than ARQ flies, showed a reduced median survival compared to similar flies exposed to normal sheep brain homogenate. These prion-induced phenotypic effects were PrP mediated since ovine prions were not toxic in non-PrP transgenic control flies. Our observations provide the basis of an invertebrate model of transmissible mammalian prion disease. PMID- 22314255 TI - BCR-ABL kinase domain mutations in tyrosine kinase inhibitors-naive and -exposed Southeast Asian chronic myeloid leukemia patients. AB - BCR-ABL kinase domain (KD) mutation is the main mechanism associated with resistance to tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML) patients. This study targeted a large cohort of CML (n=171) comprising 80 naive CML cases without prior TKI exposure as well as 91 cases undergoing 1st generation (imatinib) and/or 2nd generation (nilotinib/dasatinib) TKI therapy. KD mutations were analyzed by denaturing high performance liquid chromatography followed by direct sequencing. Twenty-one types of mutations were found in 37 patients including 13 known mutations and 8 previously unidentified mutations. Thirty cases had a single mutation while 7 cases had multiple mutations. Twenty three percent of patients receiving first-line imatinib, 69% of imatinib resistant patients receiving 2nd generation TKI, and 75% of advanced phase patients treated with front-line 2nd generation TKI had KD mutations. Interestingly, 9% of TKI-naive CML cases were also discovered to carry the KD mutations including 5 novel variants. Patients who received hydroxyurea had a 2 fold increase in KD mutations as compared to newly diagnosed patients but they still had a lower mutation frequency than TKI-exposed cases. Mutations in the naive cases were mainly localized in the C-helix domain and SH3 contact site whereas in exposed cases predominantly in the drug contact site, P-loop, and catalytic domain. T315I resistant mutation was identified only in TKI-exposed cases. In conclusion, several known and novel BCR-ABL KD mutations were discovered in the TKI-naive and -exposed Southeast Asian CML patients, supporting the concept that naturally occurring KD mutations were present in leukemic cells prior to drug exposure. T315I resistant mutation was completely undetectable in this naive Southeast Asian cohort; its incidence, however, increases with drug exposure. PMID- 22314256 TI - A new microsporidian parasite, Heterosporis saurida n. sp. (Microsporidia) infecting the lizardfish, Saurida undosquamis from the Arabian Gulf, Saudi Arabia: ultrastructure and phylogeny. AB - A new microsporidian that infects the lizardfish Saurida undosquamis (Richardson, 1848) that are caught in the Arabian Gulf in Saudi Arabia is described here. This parasite invades the skeletal muscle of the abdominal cavity forming white, cyst like structures containing numerous spores. The prevalence of the infection was 32.1% (135/420). The spores were oval to pyriform in shape and measured approximately 3.3 MUm*2.0 MUm. The developing spores were found within parasitophorous vacuoles. In mature spores, the polar filament was arranged into 5 coils in a row. Molecular analysis of the rRNA genes, including the ITS region, and phylogenetic analyses using maximum parsimony, maximum likelihood, and Bayesian inference were performed. The ultrastructural characteristics and phylogenetic analyses support the recognition of a new species, herein named Heterosporis saurida n. sp. PMID- 22314257 TI - Rationalizing the F...S interaction discovered within a tetrafluorophenylazido containing bola-phospholipid. AB - A bola-lipid bearing tetrafluorophenylazido chromophore in the diacyl chain displayed puzzling (19)F NMR, leading to the evidence and rationalization of a F...S weak interaction that is important for altering molecular structures and imposing novel and special properties on fluorinated compounds. PMID- 22314258 TI - Occupational causes of sarcoidosis. AB - PURPOSE OF REVIEW: Sarcoidosis, the multiorgan granulomatous disease of unknown cause, remains mysterious. Several important investigations in the past 2 years add to the accumulating evidence for both occupational and environmental causes of granulomatous inflammation. RECENT FINDINGS: This review considers the most recent studies that contribute to the hypothesis that sarcoidosis occurs when individuals are exposed to foreign antigens and to inorganic particulates that promote inflammation. Major recent findings, such as those emerging from the study of World Trade Center responders, the study of nanoparticles, and cases of work-associated sarcoidosis, support the probability that occupational, as well as environmental, exposures to inflammatory stimuli trigger sarcoidosis-like illness. Major recent studies of microbially rich indoor environments, including moldy indoor workplaces and mycobacterially contaminated settings, contribute to the evidence that a variety of microbial antigens serve as targets for the hypersensitivity immune response in an inflammatory milieu. SUMMARY: There is increasing evidence that sarcoidosis can occur in workplace settings in which there is exposure to both foreign antigens and inorganic triggers of inflammation that promote an exuberant granulomatous immune response. It is likely that sarcoidosis has more than one cause. PMID- 22314259 TI - Determinants of health-related quality of life in morbid obese candidates to gastric banding. AB - OBJECTIVE: To analyse determinants of self reported health-related quality of life (HR-QoL) in morbid obese patients candidates to laparoscopic adjustable gastric banding (LAGB). METHODS: Determinants of HR-QoL were investigated in 383 morbid obese patients (82 M and 301 F) with BMI>=40 kg/m2 (BMI>=35 kg/m2 if complicated obesity) and age 18-60 years. HR-QoL was determined with the SF-36 questionnaire. Determinants of the two summary measures of SF-36 (physical component and mental component) were analysed by stepwise multiple linear regression analysis with age, BMI, physical comorbidites, mental comorbidites and eating behaviour disorders as independent variables. Physical comorbities (diabetes, hypertension, hypertriglyceridemia, low HDL, sleep apnea and osteoarthritis) were coded as present or absent on the basis of simple diagnostic clinical criteria; mental comorbidities (depression) and eating behaviour disorders (binge eating, sweet eating and nibbling) on the basis of an unstructured clinical interview. RESULTS: Mean age was 38.8+/-10.2 years and mean BMI was 41.5+/-5.4 kg/m2. Scores in the eight SF-36 subscales were lower in women than in men and lower than in the general Italian population. However, 18.4-43.5% of the participants had HR-QoL levels above the normative values, depending on the scale. In both genders, low scores in the mental component of the SF-36 were associated to the presence of depression and eating behaviour disorders and not to physical comorbidities or BMI levels. Low physical self-perceived well being was associated to high BMI levels in men and to depression, hypertension and hypertriglyceridemia in women. CONCLUSION: HR-QoL was poor in morbid obese candidates to LAGB, particularly in women, and was negatively affected more by mental comorbidites and eating behaviour disorders than by physical comorbidities or BMI levels. PMID- 22314260 TI - Spherical alpha-Ni(OH)2 nanoarchitecture grown on graphene as advanced electrochemical pseudocapacitor materials. AB - This work reports a new graphene-based composite for supercapacitor material, and the maximum specific capacitance of 1760.72 F g(-1) at a scan rate of 5 mV s(-1), with excellent cycling stability. PMID- 22314261 TI - Prevalence and clinical significance of subsyndromal manic symptoms, including irritability and psychomotor agitation, during bipolar major depressive episodes. AB - BACKGROUND: There is increasing evidence that subsyndromal manic symptoms occur frequently during bipolar major depressive episodes (MDEs) and may be a subtle form of 'depressive mixed state.' This paper examines the prevalence and clinical characteristics of MDEs with subsyndromal manic symptoms. The specific effects of overt irritability and psychomotor agitation are examined. METHODS: Bipolar (type I or II) patients with an MDE at intake (N=142) were compared based on the presence or absence of concurrent subsyndromal manic symptoms. The groups were further subdivided by the presence of symptoms of overt irritability and/or psychomotor agitation. RESULTS: Subsyndromal manic symptoms during bipolar MDEs were highly prevalent (76.1%), and were associated with significantly increased severity of depression/dysphoria in the intake episode, longer episode duration, and more suicidal ideation and behavior (past, current, and during long-term follow-up). Overt irritability and psychomotor agitation were the most prevalent subsyndromal manic symptoms (co-occurring in 57% and 39% of MDEs, respectively), and accounted for most of the negative effects associated with subsyndromal manic symptoms. LIMITATIONS: The findings need to be confirmed in larger samples, which also examine the relationship to adequate antidepressant and/or mood stabilizing treatment. CONCLUSIONS: The presence of one or more subsyndromal manic symptoms appears to be the modal presentation of bipolar MDEs and a marker for a subtle form of bipolar mixed depressive state. In particular, patients with symptoms of overt irritability and/or psychomotor agitation should be monitored closely to avoid serious clinical outcomes such as longer affective episodes, exacerbation of manic symptoms syndromal mania, and heightened suicidality. PMID- 22314262 TI - Pain at age eight as a predictor of antidepressant medication use by age 24: findings from the Finnish nationwide 1981 birth cohort study. AB - BACKGROUND: The existing knowledge about long-term psychosocial consequences of childhood pain is scarce. The current study investigated childhood pain symptoms as potential risk factors for antidepressant use in adolescence and early adulthood. METHODS: A representative sample of eight-year-old children (n=6017) and their parents were asked about the prevalence of the child's headache, abdominal pain, and unspecified pain symptoms. The associations with antidepressant purchases by age 24, based on the nationwide prescription register, were analyzed separately for each symptom and each reporter. Sex, parental educational level, and child-, parent- and teacher-reported child's psychiatric symptoms at baseline were included as confounding variables. RESULTS: In the sex-adjusted model, the child's own report of headache and other pains, and the parents' report of their child's abdominal pain, predicted antidepressant purchases. When confounding variables were included in the final model, only the child's own report of headache predicted antidepressant use with a dose-response relationship. The hazard ratios and 95% confidence intervals for frequent and for almost daily headache were 1.6 (1.3-2.0) and 2.1 (1.5-2.9), respectively, in the sex-adjusted model, and 1.5 (1.2-1.8) and 1.7 (1.2-2.5) in the final model. LIMITATIONS: The assessment of each pain symptom was based on one question for each reporter. The specific indications for the described medication could not be defined. CONCLUSIONS: Health care professionals should also ask children themselves about the pain symptoms. They should be aware that children with pain are at increased risk of suffering later from conditions that require antidepressant treatment. PMID- 22314263 TI - Efficacy and safety of dextromethorphan/quinidine at two dosage levels for diabetic neuropathic pain: a double-blind, placebo-controlled, multicenter study. AB - OBJECTIVE: To evaluate dextromethorphan coadministered with quinidine as treatment of diabetic peripheral neuropathic pain. DESIGN: In a 13-week, phase 3, randomized controlled trial, 379 adults with daily symmetric diabetic peripheral neuropathy (DPN) leg pain for >=3 months received double-blind placebo, dextromethorphan/quinidine (DMQ) 45/30 mg, or DMQ 30/30 mg, administered once daily for 7 days and twice daily thereafter. Efficacy measures included four pain rating scales applied daily using patient diaries, and another two applied at five clinic visits. RESULTS: On all six scales, DMQ 45/30 mg was significantly superior to placebo, including the primary efficacy analysis, which utilized mixed-effects modeling to test all scores on an 11-point numerical Pain Rating Scale (P < 0.0001). Sensitivity analyses gave consistent results. Efficacy vs placebo was also seen for diary ratings of present pain intensity, and pain interference with sleep and with activities (all P < 0.0001). Among clinic visit assessments, DMQ 45/30 mg demonstrated greater leg pain relief (P = 0.0002) and greater reduction of leg pain intensity (P = 0.0286) vs placebo. The efficacy of DMQ 30/30 mg was numerically less than for 45/30 mg but for most outcomes remained significantly greater vs placebo. Adverse events were mostly mild or moderate and of expected types. Discontinuation for adverse events in the DMQ groups was at least twice as common as placebo. CONCLUSIONS: Throughout a 13-week trial, DMQ was effective, with an acceptable safety profile, for treatment of DPN pain. Other fixed-dose combinations of DMQ should be studied to improve overall tolerability while maintaining significant efficacy. PMID- 22314264 TI - Effects of lobaplatin as a single agent and in combination with TRAIL on the growth of triple-negative p53-mutated breast cancers in vitro. AB - Lobaplatin as a single agent and in combination with tumour necrosis factor related apoptosis-inducing ligand (TRAIL) is investigated in in-vitro models of p53-negative triple-negative breast cancers (TNBCs) and compared with a model of oestrogen receptor-positive p53-positive breast cancer. In addition, the induction of programmed cell death by lobaplatin is further explored. By using cell viability assays and western blotting, the cytotoxic effects of lobaplatin alone and in combination with TRAIL are compared with cisplatin in HCC 1806, HCC 1937, and MCF 7 cells. The multicaspase inhibitor z-VAD-fmk and necrostatin, an inhibitor of necroptosis, are used to demonstrate the mechanism of cell death caused by lobaplatin. Lobaplatin displayed antitumour activity in all three cell lines, which increased time dependently. Cotreatment of lobaplatin and TRAIL induced an increase in cytotoxicity by 30-50% in the different cell lines. The pan-caspase inhibitor z-VAD-fmk as well as necrostatin could weaken but not abolish the cytotoxic effect of lobaplatin and cisplatin. Lobaplatin showed substantial cytotoxic effects in two in-vitro models of p53-mutated TNBC. Cotreatment with TRAIL and platinum agents resulted in increased antitumour activity in the TNBC cell lines investigated. Cell death subsequent to treatment with cisplatin and lobaplatin occurred because of apoptosis. However, caspase independent mechanisms of programmed cell death were also involved. It was also demonstrated that platinum compounds could induce necroptosis, although to a minor extent. PMID- 22314265 TI - Noxa/Mcl-1 balance influences the effect of the proteasome inhibitor MG-132 in combination with anticancer agents in pancreatic cancer cell lines. AB - Pancreatic cancer progresses aggressively and owing to chemoresistance responds poorly to chemotherapy. Thus, there is an urgent need to understand the mechanisms of cancer cell resistance to generate effective strategies to circumvent intrinsic chemoresistance in this tumour indication. In this study, three pancreatic cancer cell lines, MIA PaCa-2, MDAPanc-3 and AsPC-1, were treated with the proteasome inhibitor MG-132 together with camptothecin, doxorubicin or paclitaxel, and cytotoxicity was measured using the 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The combination of MG-132 and camptothecin at a ratio of 5 : 1 gave the most promising results and enhanced cytotoxicity compared with the single compounds in MIA PaCa-2 cells. The increase was shown to be due to enhanced caspase-3 activity resulting in apoptosis. Moreover, this combination upregulated the levels of the proapoptotic protein Noxa and reduced the levels of the antiapoptotic protein Mcl-1, as demonstrated by western blotting. In contrast, the combination of MG-132 with doxorubicin also induced increased cytotoxicity, but apoptosis was decreased. The lack of an enhanced apoptosis induction could be correlated with high levels of Mcl-1 in response to the combined treatment with MG-132 and doxorubicin. Thus, the results indicate that regulation of the antiapoptotic and proapoptotic Bcl-2 family members Noxa and Mcl-1 is predicative of the effectiveness of the combination of MG-132 with different anticancer agents on apoptosis induction in pancreatic cancer cells. PMID- 22314266 TI - Polyanionic N-donor ligands as chelating agents in transition metal complexes: synthesis, structural characterization and antiviral properties against HIV. AB - We describe here the synthesis and characterization of new sulfonated and carboxylated-containing N-donor ligands [Na(4)(edts)].4H(2)O (2), [Na(2)(dmeddp)].2H(2)O (3) and [Na(4)(edtp)].H(2)O (4) (edts = ethylene-diamine- N,N,N',N'-tetraethylenesulfonate ion; dmeddp = dimethyl-ethylene-diamine N,N,N',N'-tetra-3-propionate ion; edtp = ethylene-diamine-N,N,N',N'-tetra-3 propionate ion) and their corresponding metal (Ni, Co, Cu and Zn) complexes. Mainly, UV-Vis and a computer aided analysis of the EPR spectra provided information on the geometry and structure of the complexes in solution. Some of the metal complexes inhibit HIV replication when treating both pre- and post infected PBMC cells, and hustle the inhibitory effect compared to the metal salts alone. PMID- 22314267 TI - The profile of hippocampal metabolites differs between Alzheimer's disease and subcortical ischemic vascular dementia, as measured by proton magnetic resonance spectroscopy. AB - Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SIVD) have overlapping pathologies and risk factors, but their underlying neurodegenerative mechanisms are basically different. We performed magnetic resonance spectroscopy (MRS) to study metabolite differences between the two diseases in vivo. The subjects were 31 patients with SIVD and 99 with AD. Additionally, 45 elderly subjects were recruited as controls. We measured N-acetylaspartate (NAA), glutamine and glutamate (Glx), and myoinositol (mIns) concentration quantitatively using a 1.5-T MR scanner. N-acetylaspartate and Glx concentrations decreased in the hippocampus and cingulate/precuneal cortices (PCC) in both AD and SIVD patients, and the NAA decrease in the hippocampus was more prominent in AD than in SIVD. Interestingly, the pattern of mIns concentration changes differed between the two disorders; mIns was increased in AD but not increased in SIVD. If one differentiates between AD and SIVD by the mIns concentration in the hippocampus, the area under the receiver operating characteristic curve was 0.95, suggesting a high potential for discrimination. Our results suggest that proton MRS can provide useful information to differentiate between AD and SIVD. The difference of mIns concentrations in the hippocampus and PCC seems to reflect the different neurodegenerative mechanisms of the two disorders. PMID- 22314268 TI - Pro-angiogenic effects of resveratrol in brain endothelial cells: nitric oxide mediated regulation of vascular endothelial growth factor and metalloproteinases. AB - Resveratrol may be a powerful way of protecting the brain against a wide variety of stress and injury. Recently, it has been proposed that resveratrol not only reduces brain injury but also promotes recovery after stroke. But the underlying mechanisms are unclear. Here, we tested the hypothesis that resveratrol promotes angiogenesis in cerebral endothelial cells and dissected the signaling pathways involved. Treatment of cerebral endothelial cells with resveratrol promoted proliferation, migration, and tube formation in Matrigel assays. Consistent with these pro-angiogenic responses, resveratrol altered endothelial morphology resulting in cytoskeletal rearrangements of beta-catenin and VE-cadherin. These effects of resveratrol were accompanied by activation of phosphoinositide 3 kinase (PI3-K)/Akt and Mitogen-Activated Protein Kinase (MAPK)/ERK signaling pathways that led to endothelial nitric oxide synthase upregulation and increased nitric oxide (NO) levels. Subsequently, elevated NO signaling increased vascular endothelial growth factor and matrix metalloproteinase levels. Sequential blockade of these signaling steps prevented resveratrol-induced angiogenesis in cerebral endothelial cells. These findings provide a mechanistic basis for the potential use of resveratrol as a candidate therapy to promote angiogenesis and neurovascular recovery after stroke. PMID- 22314269 TI - Junctional protein regulation by sphingosine kinase 2 contributes to blood-brain barrier protection in hypoxic preconditioning-induced cerebral ischemic tolerance. AB - Protection of the blood-brain barrier (BBB) is correlated with improved outcome in stroke. Sphingosine kinase (SphK)-directed production of sphingosine-1 phosphate, which we previously documented as being vital to preconditioning induced stroke protection, mediates peripheral vascular integrity via junctional protein regulation. We used a hypoxic preconditioning (HPC) model in adult wild type and SphK2-null mice to examine the isoform-specific role of SphK2 signaling for ischemic tolerance to transient middle cerebral artery occlusion and attendant BBB protection. Reductions in infarct volume and BBB permeability in HPC-treated mice were completely lost in SphK2-null mice. Hypoxic preconditioning induced attenuation of postischemic BBB disruption in wild types, evidenced by reduced extravascular immunoglobulin G intensity, suggests direct protection of BBB integrity. Measurement of BBB junctional protein status in response to HPC revealed SphK2-dependent increases in triton-insoluble claudin-5 and VE-cadherin, which may serve to strengthen the BBB before stroke. Postischemic loss of VE cadherin, occludin, and zona occludens-1 in SphK2-null mice with prior HPC suggests that SphK2-dependent protection of these adherens and tight junction proteins is compulsory for HPC to establish a vasculoprotective phenotype. Further elucidation of the mediators of this endogenous, HPC-activated lipid signaling pathway, and their role in protecting the ischemic BBB, may provide new therapeutic targets for cerebrovascular protection in stroke patients. PMID- 22314270 TI - Suppression of three dimensional twinning for a 100% yield of vertical GaAs nanowires on silicon. AB - Multiple seed formation by three-dimensional twinning at the initial stages of growth explains the manifold of orientations found when self-catalyzed GaAs nanowires grow on silicon. This mechanism can be tuned as a function of the growth conditions by changing the relative size between the GaAs seed and the Ga droplet. We demonstrate how growing under high V/III ratio results in a 100% yield of vertical nanowires on silicon(111). These results open up the avenue towards the efficient integration of III-V nanowire arrays on the silicon platform. PMID- 22314271 TI - Evaluating ESWL-induced renal injury based on urinary TNF-alpha, IL-1alpha, and IL-6 levels. AB - Extracorporeal shockwave lithotripsy (ESWL) has dramatically changed the treatment of urinary lithiasis and has been the first treatment option for the majority of patients for more than two decades. Despite its significant benefits, it induces acute renal injury that extends from the papilla to the outer cortex. We evaluated the severity of the inflammatory response to ESWL by measuring the urinary excretion of the cytokines TNF-alpha, IL-1alpha, and IL-6. The study included 21 selected patients and 14 control subjects. All patients underwent the same ESWL procedure (2,500 shockwaves at 100 shockwaves/min and 0.039 J from the lithotripter). Urine TNF-alpha, IL-1alpha, and IL-6 levels were measured using standard ELISA kits. In the study population (patients and controls), we did not detect TNF-alpha in the urine samples. The levels of both IL-1alpha (2.5 pg/ml) and IL-6 (3.8 pg/ml) measured before ESWL were not significantly different from the control group (2.5 and 5.2 pg/ml, respectively; p > 0.05). Twenty-four hours after ESWL, in contrast to IL-1alpha (4 pg/ml), urine IL-6 (19.7 pg/ml) increased significantly (p < 0.05). Fourteen days after ESWL, IL-1alpha increased to 5 pg/ml, while IL-6 (7 pg/ml) decreased to the control level. Urine cytokine levels may be used to evaluate the inflammatory response to ESWL. After ESWL, IL-6 levels increased in the early phase, while IL-1alpha levels increased later. These two markers may be used to measure the severity of inflammation. In contrast to IL-1alpha and IL-6, urine TNF-alpha excretion was not increased by ESWL. We believe that the inflammatory response to ESWL can be detected by the urinary excretion of IL-1alpha for up to 14 days. PMID- 22314272 TI - Tryptophan tryptophylquinone biosynthesis: a radical approach to posttranslational modification. AB - Protein-derived cofactors are formed by irreversible covalent posttranslational modification of amino acid residues. An example is tryptophan tryptophylquinone (TTQ) found in the enzyme methylamine dehydrogenase (MADH). TTQ biosynthesis requires the cross-linking of the indole rings of two Trp residues and the insertion of two oxygen atoms onto adjacent carbons of one of the indole rings. The diheme enzyme MauG catalyzes the completion of TTQ within a precursor protein of MADH. The preMADH substrate contains a single hydroxyl group on one of the tryptophans and no crosslink. MauG catalyzes a six-electron oxidation that completes TTQ assembly and generates fully active MADH. These oxidation reactions proceed via a high valent bis-Fe(IV) state in which one heme is present as Fe(IV)=O and the other is Fe(IV) with both axial heme ligands provided by amino acid side chains. The crystal structure of MauG in complex with preMADH revealed that catalysis does not involve direct contact between the hemes of MauG and the protein substrate. Rather it is accomplished through long-range electron transfer, which presumably generates radical intermediates. Kinetic, spectrophotometric, and site-directed mutagenesis studies are beginning to elucidate how the MauG protein controls the reactivity of the hemes and mediates the long range electron/radical transfer required for catalysis. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology. PMID- 22314274 TI - Robotic-assisted total mesorectal excision with the aid of a single-port device. AB - INTRODUCTION AND INDICATIONS: Robotic surgery has numerous advantages in rectal cancer surgery. Studies have reported the advantages associated with single-port approaches, such as eliminating the need for additional incisions, as well as the difficulties inherent in this technique. The authors present a hybrid technique that they performed using a robotic total mesorectal excision with the aid of a single port-device. Materials and methods. The authors performed the technique on 2 patients using a single-port device through an umbilical incision and 3 accessory ports for the robotic arms. There was no need to place ports for the assistant's equipment or for an assistant incision. RESULTS AND COMPLICATIONS: The operation time was 177.5 minutes, and there were no intraoperative or postoperative complications. Both patients were discharged 7 days after the operation. CONCLUSIONS: This technical variation is an additional step forward for oncological surgery with minimal damage to the abdominal wall. PMID- 22314273 TI - Use of stance time variability for predicting mobility disability in community dwelling older persons: a prospective study. AB - BACKGROUND AND PURPOSE: Mobility disability is a serious and frequent adverse health outcome associated with aging. Early identification of individuals at risk for mobility disability is important if interventions to prevent disability are to be instituted. The objectives of this prospective study were to (1) determine the magnitude of stance time variability (STV) that discriminates individuals who currently have mobility disability (prevalent mobility disability) and (2) determine the magnitude of STV that predicts a new onset of mobility disability at 1 year (incident mobility disability). METHODS: A total of 552 community dwelling older adults were evaluated as part of the Cardiovascular Health Study, a longitudinal cohort study. Stance time, in milliseconds, was determined from 2 passes on a 4-m computerized walkway at self-selected walking speed, and STV was defined as the standard deviation from approximately 12 individual steps. Mobility disability was defined as self-reported difficulty walking a one-half mile. Receiver operating characteristic (ROC) curves were plotted to determine an optimal cutoff value for STV for prevalent and incident mobility disability, and the area under the receiver operating characteristic curve (AUC) was computed. RESULTS: The optimal cutoff score for STV (maximizing sensitivity and specificity) for prevalent mobility disability was 0.037 seconds (sensitivity = 65%, specificity = 65%, AUC = 0.70) and for incident 1-year mobility disability was 0.034 seconds (sensitivity = 61%, specificity = 60%, AUC = 0.65). The use of likelihood ratios demonstrated a gradient of risk across values of STV, with mobility risk increasing as values of STV increased. DISCUSSION AND CONCLUSION: Values of STV may be useful in identifying older adults with mobility disability and at risk for future disability. We recommend the more conservative estimate for identifying risk, STV = 0.034 seconds, which maximizes the sensitivity and minimizes false negatives. The relatively modest values on the validity indices could possibly be improved by increasing the reliability of the measurement of STV. Clinicians should interpret the cutoff values liberally and use STV in conjunction with other measures until further work is completed to validate STV as an indicator of mobility disability. PMID- 22314275 TI - Psychometric properties of the Perception of Teasing Scale in a Spanish adolescent sample: POTS-S. AB - The present study examines the psychometric properties of the Spanish version of the Perception of Teasing Scale (POTS-S). Participants were 1559 adolescents. They completed a translated version of the POTS and versions validated in Spanish population of the Rosenberg Self-Esteem Scale, the Body Dissatisfaction and Drive for Thinness subscales of the Eating Disorders Inventory-2, and the Children's Eating Attitudes Test. The results showed that the POTS-S retains the original structure of two factors, weight and competency, with satisfactory fit indices. The POTS-S constitutes a shorter questionnaire than the original version; specifically, it consists of 9 items instead of 11. The POTS-S showed good internal consistency and satisfactory test-retest stability. The relationship between the weight subscale and the variables related to eating and weight were statistically significant. As regards the competency subscale, the correlations were all lower than those for the weight subscale, except in the case of the self esteem variable. The POTS-S showed good psychometric properties, indicating its suitability as an instrument for assessing the perception of teasing in Spanish adolescents. PMID- 22314276 TI - ATX and LPA receptor 3 are coordinately up-regulated in lipopolysaccharide stimulated THP-1 cells through PKR and SPK1-mediated pathways. AB - Lysophosphatidic acid (LPA) is an important phospholipid mediator in inflammation and immunity. Previously, we showed that autotaxin (ATX), the enzyme producing LPA from lysophosphatidylcholine (LPC), is induced by LPS in THP-1 cells via the activation of PKR, JNK and p38 MAPK. In this study, we find that ATX and LPA receptor 3 (LPA(3)) are coordinately up-regulated in LPS-stimulated THP-1 cells. PKR-mediated activation of JNK1 and p38 MAPK is required for both ATX and LPA(3) up-regulation. SPK1-mediated activation of the PI3K-AKT-beta-catenin pathway is essential for ATX induction, while SPK1-mediated ERK activation is required for LPA(3) up-regulation. Either ATX or LPA(3) knockdown inhibited CCL8 induction by LPS, suggesting that ATX and LPA(3) are involved in CCL8 induction during the inflammatory process against bacterial infection. PMID- 22314277 TI - Relationship and prognostic value of microvascular obstruction and infarct size in ST-elevation myocardial infarction as visualized by magnetic resonance imaging. AB - BACKGROUND: Both infarct size and microvascular obstruction (MO) assessed by cardiac magnetic resonance imaging (CMR) are known to be predictors for adverse clinical outcome after ST-elevation myocardial infarction (STEMI). We hypothesized that a ratio of MO and infarct size (MO/infarct size) might be an even stronger predictor for outcome after STEMI, which has not been investigated yet. METHODS: STEMI patients reperfused by primary angioplasty (n = 438) within 12 h after symptom onset underwent contrast-enhanced CMR at a median of 3 days (interquartile range [IQR] 2;4) after the index event. MO and infarct size were measured 15 min after intravenous gadolinium injection. Follow-up was conducted after 19 months (IQR 10;27). The primary end point was defined as a composite of death, non-fatal myocardial reinfarction and congestive heart failure (major adverse cardiac events [MACE]). RESULTS: The extent of MO was only weakly correlated with infarct size (r = 0.21, p < 0.001). In a first multivariate analysis including extent of MO, infarct size, ejection fraction, end-systolic and end-diastolic volume, the extent of MO was independently associated with MACE (hazard ratio [HR] 1.03, 95%CI 1.02-1.05, p < 0.001). In a second multivariate analysis including MO/infarct size on top of the extent of MO, infarct size, ejection fraction, end-systolic and end-diastolic volume, MO/infarct size was identified as the strongest independent predictor for MACE (HR 2.22 [95%CI 1.60 3.08, p < 0.001]). CONCLUSIONS: In contrast to infarct size, MO is associated with adverse clinical outcome after STEMI even after adjustment for other CMR parameters. However, MO/infarct size is a more powerful predictor for long-term outcome after STEMI than either parameter alone. PMID- 22314278 TI - Psychosocial impact of implantable cardioverter defibrillators (ICD) in young adults with Tetralogy of Fallot. AB - OBJECTIVE: To investigate the psychosocial impact of having an implantable cardioverter defibrillator (ICD) in adults with Tetralogy of Fallot (ToF). METHODS: Included were 26 ToF-patients with an ICD (age 44 +/- 12 years), and two control groups consisting of 28 ToF-patients without an ICD (age 40 +/- 10 years) and a group of 35 ICD-patients of older age without ToF (age 72.0 +/- 8 years). This last control group was chosen to represent the "older general ICD population" with acquired heart disease seen at the out-patient clinic. Psychosocial functioning encompassed daily functioning, subjective health status, quality of life, anxiety, depression, coping and social support. RESULTS: ToF patients with ICD showed diminished psychosocial functioning in comparison to ToF patients without ICD. This was reflected by diminished subjectively perceived physical functioning (p = 0.01), general health perception (p < 0.01) and a lower satisfaction with life (p = 0.02). In comparison to older ICD-patients, ToF patients with ICD showed less satisfaction with life (p = 0.03), experienced more anxiety (p = 0.01) and showed less favourable coping styles, although physical functioning was better for ToF-patients with ICD than for older ICD-patients (p = 0.01). More inappropriate shocks were found in ToF-patients with ICD compared to the older ICD-patients. CONCLUSION: In patients with ToF, ICD implantation had a major impact on psychosocial functioning which should be taken into account when considering ICD implantation in these young patients. To help improve psychosocial functioning, psychological counselling attuned to the specific needs of these patients may be useful. PMID- 22314279 TI - Evaluation of late cognitive impairment and anxiety states following traumatic brain injury in mice: the effect of minocycline. AB - Comorbidity of cognitive and stress disorders is a common clinical sequel of traumatic brain injury (TBI) that is essentially determined by the site and severity of the insult, but also by the extent of the ensuing neuroinflammatory response. The present study sought to examine the late effects of closed-head TBI on memory function and anxiety in mice, in order to further examine the potential efficacy of an acute anti-inflammatory treatment with minocycline. The mouse model of closed-head injury by mechanical percussion was applied on anesthetized Swiss mice. The treatment protocol included three injections of minocycline (i.p.) at 5 min (90 mg/kg), 3 h and 9 h (45 mg/kg) post-TBI. The Novel Object Recognition Test as well as the Elevated Plus Maze (EPM) and Elevated Zero Maze (EZM) tasks were employed to assess post-TBI memory and anxiety respectively. Our results revealed a recognition memory deficit that was significant up to at least 13 weeks post-TBI. However, neither EPM nor EZM revealed any alteration in post TBI anxiety levels albeit some mild disinhibition. Most importantly, minocycline was able to attenuate the memory impairment in an effective and lasting manner, highlighting its therapeutic potential in TBI. PMID- 22314280 TI - Electrochemical performance of a novel ionic liquid derived mesoporous carbon. AB - A novel nano-fibrillated mesoporous carbon (IFMC) was found to be an effective modifier in combination with ionic liquid 1-octylpyridinum hexafluorophosphate (OPFP) as a binder to give impregnated graphite electrodes with outstanding electrochemical performances. PMID- 22314281 TI - Non-invasive microCT imaging characterization and in vivo targeting of BB2 receptor expression of a PC-3 bone metastasis model. AB - PURPOSE: A devastating progression of human prostate cancer is the development of bone metastasis. Animal models of bone metastasis induced by inoculating human prostate cell lines into mice are well established. Here, we report the characterization of a mouse model of prostatic bone metastasis using non-invasive microCT and targeted microSPECT imaging of bone tumors using the bombesin receptor (BB2r)-avid radiolabeled peptide, (111)In-DOTA-8-Aoc-BBN[7-14]NH(2). PROCEDURES: Immunocompromised mice were inoculated with human prostate cancer cells by intracardiac injection. Metastatic lesion development was monitored by serially imaging mice weekly with microCT. Mice with CT imaging-confirmed bone lesions were administered (111)In-DOTA-8-Aoc-BBN[7-14]NH(2) for microSPECT imaging of BB2r expressing lesions. RESULTS: Metastatic bone lesions as small as 0.3 mm in diameter were detected by microCT image analysis as early as 21 days after tumor cell inoculation and had wide anatomical distribution. MicroSPECT imaging using (111)In-DOTA-8-Aoc-BBN[7-14]NH(2) successfully targeted BB2r expressing metastatic bone lesions of the tibia at day 29. CONCLUSIONS: MicroCT imaging can accurately and non-invasively follow the onset and progression of metastatic bone lesions in mouse models of prostate cancer. Micro-CT coupled with BB2r Micro-SPECT imaging affords the opportunity to obtain a combined receptor/anatomic map of metastatic bone lesion status in this mouse model. PMID- 22314287 TI - Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti invasive and in vivo anti-metastatic activities. AB - Cancer metastasis refers to the spread of cancer cells from the primary neoplasm to distant sites, where secondary tumors are formed, and is the major cause of death from cancer. Natural phytochemicals containing phenolic compounds have been widely demonstrated to have the capability to prevent cancer metastasis. Among phenolic compounds, flavonoids are a very large subclass, and they are abundant in food and nutraceuticals. The number of reports demonstrating that flavonoids are an effective natural inhibitor of cancer invasion and metastasis is increasing in the scientific literature. Catechin derivatives, (-) epigallocatechin-3-gallate, (-)-epigallocatechin, (-)-epicatechin-3-gallate,and ( )-epicatechin, are the most studied compounds in this topic so far; genistein/genistin, silibinin, quercetin, and anthocyanin have also been widely investigated for their inhibitory activities on invasion/metastasis. Other flavonoids in dietary vegetable foods that are responsible for anti-invasive and anti-metastatic activities of tumors include luteolin,apigenin, myricetin, tangeretin, kaempferol, glycitein, licoricidin,daidzein, and naringenin. To effectively overcome the metastatic cascade, including cell-cell attachment, tissue barrier degradation, migration, invasion, cell-matrix adhesion,and angiogenesis, it is essential that a bioactive compound prevent tumor cells from metastasizing. This review summarizes the effects of flavonoids on the metastatic cascade and the related proteins, the in vitro anti-invasive activity of flavonoids against cancer cells, and the effects of flavonoids on antiangiogenic and in vivo anti-metastatic models. The available scientific evidence indicates that flavonoids are a ubiquitous dietary phenolics subclass and exert extensive in vitro anti-invasive and in vivo anti-metastatic activities. PMID- 22314289 TI - SHAPE-directed discovery of potent shRNA inhibitors of HIV-1. AB - The RNA interference (RNAi) pathway can be exploited using short hairpin RNAs (shRNAs) to durably inactivate pathogenic genes. Prediction of optimal target sites is notoriously inaccurate and current approaches applied to HIV-1 show weak correlations with virus inhibition. In contrast, using a high-content model for disrupting pre-existing intramolecular structure in the HIV-1 RNA, as achievable using high-resolution SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) chemical probing information, we discovered strong correlations between inhibition of HIV-1 production in a quantitative cell-based assay and very simple thermodynamic features in the target RNA. Strongest inhibition occurs at RNA target sites that both have an accessible "seed region" and, unexpectedly, are structurally accessible in a newly identified downstream flanking sequence. We then used these simple rules to create a new set of shRNAs and achieved inhibition of HIV-1 production of 90% or greater for up to 82% of designed shRNAs. These shRNAs inhibit HIV-1 replication in therapy-relevant T cells and show no or low cytotoxicity. The remarkable success of this straightforward SHAPE based approach emphasizes that RNAi is governed, in significant part, by very simple, predictable rules reflecting the underlying RNA structure and illustrates principles likely to prove broadly useful in understanding transcriptome-scale biological recognition and therapeutics involving RNA. PMID- 22314288 TI - Regulation of stem cell plasticity: mechanisms and relevance to tissue biology and cancer. AB - Embryonic stem cells (ESCs) are associated with a high degree of plasticity, which allows them to self-renew and differentiate into every somatic cell. During differentiation, ESCs follow a hierarchically organized pattern towards tissue specificity, which ultimately results in permanent cell cycle arrest and a loss of cellular plasticity. In contrast to their normal somatic counterparts, cancer cells retain elevated levels of plasticity that include switches between epithelial and mesenchymal phenotypes. Transitions between these cell stages have lately been linked to the reacquisition of stem cell features during cellular reprogramming and dedifferentiation in normal and neoplastic cells. In this review, we discuss the key factors and their interplay that is needed to regain a stem cell stage with a particular emphasis put on the impact of cell cycle regulation. Apart from mechanistic insights into the emerging fundamental processes of stem cell plasticity and capacity to transdifferentiate, we also highlight implications of these concepts for tissue biology, tumorigenesis, and cancer therapy. PMID- 22314290 TI - Microvesicle-associated AAV vector as a novel gene delivery system. AB - Adeno-associated virus (AAV) vectors have shown remarkable efficiency for gene delivery to cultured cells and in animal models of human disease. However, limitations to AAV vectored gene transfer exist after intravenous transfer, including off-target gene delivery (e.g., liver) and low transduction of target tissue. Here, we show that during production, a fraction of AAV vectors are associated with microvesicles/exosomes, termed vexosomes (vector-exosomes). AAV capsids associated with the surface and in the interior of microvesicles were visualized using electron microscopy. In cultured cells, vexosomes outperformed conventionally purified AAV vectors in transduction efficiency. We found that purified vexosomes were more resistant to a neutralizing anti-AAV antibody compared to conventionally purified AAV. Finally, we show that vexosomes bound to magnetic beads can be attracted to a magnetized area in cultured cells. Vexosomes represent a unique entity which offers a promising strategy to improve gene delivery. PMID- 22314291 TI - Enhancing muscle membrane repair by gene delivery of MG53 ameliorates muscular dystrophy and heart failure in delta-Sarcoglycan-deficient hamsters. AB - Muscular dystrophies (MDs) are caused by genetic mutations in over 30 different genes, many of which encode for proteins essential for the integrity of muscle cell structure and membrane. Their deficiencies cause the muscle vulnerable to mechanical and biochemical damages, leading to membrane leakage, dystrophic pathology, and eventual loss of muscle cells. Recent studies report that MG53, a muscle-specific TRIM-family protein, plays an essential role in sarcolemmal membrane repair. Here, we show that systemic delivery and muscle-specific overexpression of human MG53 gene by recombinant adeno-associated virus (AAV) vectors enhanced membrane repair, ameliorated pathology, and improved muscle and heart functions in delta-sarcoglycan (delta-SG)-deficient TO-2 hamsters, an animal model of MD and congestive heart failure. In addition, MG53 overexpression increased dysferlin level and facilitated its trafficking to muscle membrane through participation of caveolin-3. MG53 also protected muscle cells by activating cell survival kinases, such as Akt, extracellular signal-regulated kinases (ERK1/2), and glycogen synthase kinase-3beta (GSK-3beta) and inhibiting proapoptotic protein Bax. Our results suggest that enhancing the muscle membrane repair machinery could be a novel therapeutic approach for MD and cardiomyopathy, as demonstrated here in the limb girdle MD (LGMD) 2F model. PMID- 22314292 TI - BioKnife, a uPA activity-dependent oncolytic Sendai virus, eliminates pleural spread of malignant mesothelioma via simultaneous stimulation of uPA expression. AB - Malignant pleural mesothelioma (MPM) is highly intractable and readily spreads throughout the surface of the pleural cavity, and these cells have been shown to express urokinase-type plasminogen activator receptor (uPAR). We here examined the potential of our new and powerful recombinant Sendai virus (rSeV), which shows uPAR-specific cell-to-cell fusion activity (rSeV/dMFct14 (uPA2), named "BioKnife"), for tumor cell killing in two independent orthotopic xenograft models of human. Multicycle treatment using BioKnife resulted in the efficient rescue of these models, in association with tumor-specific fusion and apoptosis. Such an effect was also seen on both MSTO-211H and H226 cells in vitro; however, we confirmed that the latter expressed uPAR but not uPA. Of interest, infection with BioKnife strongly facilitated the uPA release from H226 cells, and this effect was completely abolished by use of either pyrrolidine dithiocarbamate (PDTC) or BioKnife expressing the C-terminus-deleted dominant negative inhibitor for retinoic acid-inducible gene-I (RIG-IC), indicating that BioKnife-dependent expression of uPA was mediated by the RIG-I/nuclear factor-kappaB (NF-kappaB) axis, detecting RNA viral genome replication. Therefore, these results suggest a proof of concept that the tumor cell-killing mechanism via BioKnife may have significant potential to treat patients with MPM that is characterized by frequent uPAR expression in a clinical setting. PMID- 22314294 TI - Rational preoperative blood type and screen testing criteria. PMID- 22314293 TI - Unresponsiveness ? unconsciousness. AB - Consciousness is subjective experience. During both sleep and anesthesia, consciousness is common, evidenced by dreaming. A defining feature of dreaming is that, while conscious, we do not experience our environment; we are disconnected. Besides inducing behavioral unresponsiveness, a key goal of anesthesia is to prevent the experience of surgery (connected consciousness), by inducing either unconsciousness or disconnection of consciousness from the environment. Review of the isolated forearm technique demonstrates that consciousness, connectedness, and responsiveness uncouple during anesthesia; in clinical conditions, a median 37% of patients demonstrate connected consciousness. We describe potential neurobiological constructs that can explain this phenomenon: during light anesthesia the subcortical mechanisms subserving spontaneous behavioral responsiveness are disabled but information integration within the corticothalamic network continues to produce consciousness, and unperturbed norepinephrinergic signaling maintains connectedness. These concepts emphasize the need for developing anesthetic regimens and depth of anesthesia monitors that specifically target mechanisms of consciousness, connectedness, and responsiveness. PMID- 22314295 TI - Mast cells: source of inflammation in complex regional pain syndrome? PMID- 22314296 TI - Leading into the future: the 50th annual Rovenstine lecture. PMID- 22314297 TI - Pore helix domain is critical to camphor sensitivity of transient receptor potential vanilloid 1 channel. AB - BACKGROUND: The recent discovery that camphor activates and strongly desensitizes the capsaicin-sensitive and noxious heat-sensitive channel transient receptor potential vanilloid subfamily member 1 (TRPV1) has provided new insights and opened up new research paths toward understanding why this naturally occurring monoterpene is widely used in human medicine for its local counter-irritant, antipruritic, and anesthetic properties. However, the molecular basis for camphor sensitivity remains mostly unknown. The authors attempt to explore the nature of the activation pathways evoked by camphor and narrow down a putative interaction site at TRPV1. METHODS: The authors transiently expressed wild-type or specifically mutated recombinant TRPV1 channels in human embryonic kidney cells HEK293T and recorded cation currents with the whole cell, patch clamp technique. To monitor changes in the spatial distribution of phosphatidylinositol 4,5 bisphosphate, they used fluorescence resonance energy transfer measurements from cells transfected with the fluorescent protein-tagged pleckstrin homology domains of phospholipase C. RESULTS: The results revealed that camphor modulates TRPV1 channel through the outer pore helix domain by affecting its overall gating equilibrium. In addition, camphor, which generally is known to decrease the fluidity of cell plasma membranes, may also regulate the activity of TRPV1 by inducing changes in the spatial distribution of phosphatidylinositol-4,5 bisphosphate on the inner leaflet of the plasma membrane. CONCLUSIONS: The findings of this study provide novel insights into the structural basis for the modulation of TRPV1 channel by camphor and may provide an explanation for the mechanism by which camphor modulates thermal sensation in vivo. PMID- 22314298 TI - Cardiac amyloidosis: what are the indications for transplant? AB - PURPOSE OF REVIEW: We review the clinical and pathological features of the various types of amyloid that involve the heart, the diagnostic utility of endomyocardial biopsy, and the experience of patient survival and disease recurrence following cardiac transplant for amyloidosis. RECENT FINDINGS: Patient outcome is dependent on arresting the cause of amyloid as well as controlling the accumulated damage, which may involve multiple organs. As such, the stratification of patient suitability for cardiac transplant must be considered in conjunction with concurrent treatments, which may include autologous stem cell, liver or kidney transplant, and chemotherapy. SUMMARY: As the efficacy of these therapies changes, the indications for cardiac transplantation need to be re-evaluated. PMID- 22314299 TI - Imaging the failing right ventricle. AB - PURPOSE OF REVIEW: This article will review the noninvasive modalities currently available for imaging the right ventricle, including two-dimensional echocardiography, cardiac magnetic resonance (CMR), multidetector computed tomography (MDCT), radionuclide ventriculography (RNV) and PET. RECENT FINDINGS: Improvements in established imaging techniques, as well as development of newer imaging modalities, have shed light on the right ventricle's adaptation to pressure and volume overload states and have allowed better prognostication in patients with right ventricular failure (RVF). SUMMARY: As therapies are developed to alter the natural history of RVF, a better understanding of the imaging modalities for the assessment of right ventricular morphology and function is needed. This review will provide an approach to investigating the patient with suspected RVF and highlight the strengths and weakness of each imaging modality. PMID- 22314300 TI - Current world literature. PMID- 22314302 TI - Determination of the distance-dependent viscosity of mixtures in parallel slabs using non-equilibrium molecular dynamics. AB - We generalize a technique for determination of the shear viscosity of mixtures in planar slabs using non-equilibrium computer simulations by applying an external force parallel to the surface generating Poiseuille flow. The distance-dependent viscosity of the mixture, given as a function of the distance from the surface, is determined by analysis of the resulting velocity profiles of all species. We present results for a highly non-ideal water + methanol mixture in the whole concentration range between rutile (TiO(2)) walls. The bulk results are compared to the existing equilibrium molecular dynamics and experimental data while the inhomogeneous viscosity profiles at the interface are interpreted using the structural data and information on hydrogen bonding. PMID- 22314303 TI - Vitamin D concentration and deficiency across different ages and genders. AB - BACKGROUND AND AIMS: Vitamin D deficiency is a major health problem worldwide, especially in the elderly, so that an accurate assessment of its prevalence is essential for planning reliable healthcare policy throughout the lifespan. The aim of the present study was to assess the concentration as well as the mild and moderate deficiencies of 25-hydroxyvitamin D (25OHD) across different ages and genders. METHODS: We searched the database of the local Laboratory Information System to retrieve results of 25OHD tests performed on the whole cohort of presumably healthy Caucasian outpatients aged >12 yrs, who were referred to our laboratory in the North-East of Italy for routine laboratory testing ordered by general practitioners, over a 3-year period (October 2008-October 2011). RESULTS: Cumulative results for 25OHD testing were retrieved for 2327 outpatients (1744 females and 583 males). No significant differences between females and males were observed for 25OHD values (71 [25-140] vs 67 [27-130] nmol/L; p=0.40), as well as a similar prevalence of mild (32.8 vs 33.4%; p=0.89) and moderate (21.7 vs 25.6%; p=0.37) 25OHD deficiency. A non significant variation of 25OHD values was also found by ANOVA analysis throughout four age cohorts (<21, 21-40, 41-60 and >60 yrs), in both genders. In each age group, the values of 25OHD did not significantly differ between genders. The percentage of subjects displaying mild and moderate 25OHD deficiencies in the older subgroup was comparable to that observed in the younger adult population. CONCLUSIONS: The results of this large epidemiological investigation show that the prevalence of mild and moderate vitamin D deficiency does not significantly increase with aging and seems lower than that observed in other European and American countries. PMID- 22314304 TI - Endothelial progenitor cell-based therapy for hemophilia A. AB - As shown by the results of both pre-clinical and clinical studies reported in past decades, the goal of establishing an effective and successful gene therapy for hemophilia A remains feasible and realistic. However, at this time, no single approach has been shown to be clearly superior, and a number of recurring challenges remain to be overcome. Given the persistent problems presented by the host immune response to systemic in vivo gene delivery, and the additional obstacles of inadequate transgene delivery and expression, we propose a re evaluation of an ex vivo gene transfer approach that utilizes a genetically modified stem cell population. In this strategy, autologous blood outgrowth endothelial progenitor cells are obtained from hemophilic animals, into which a normal copy of the factor VIII gene is introduced via an engineered virus. Cell numbers are expanded in culture prior to their re-implantation under the skin of the hemophilic animals in an artificially developed supporting environment. Follow-up assessment of the treatment involves the general evaluation of clotting activity, the specific measurement of factor VIII levels in the blood, and clinical observation. PMID- 22314305 TI - Metal complexes as templates: syntheses, structures, and luminescent properties of two zinc phosphonocarboxylates with ABW-zeolite topology. AB - Two novel zinc phosphonocarboxylates, Zn(3)(pbc)(2)(bpy)(H(2)O).H(2)O (1) and Zn(2)(pbc)(2).Zn(bpy)(H(2)O)(4).2H(2)O (2) (pbc = 4-phosphono-benzoic acid, bpy = 2,2'-bipyridine), were hydrothermally synthesized and structurally characterized. Both of them exhibit zeolitic ABW topology in which double-zigzag inorganic chains are cross-linked by the organic parts. It is notable that the metal complex Zn(bpy)(H(2)O)(x) plays different roles in the two compounds. In 1, the Zn(bpy)(H(2)O) units coordinate with the phosphonate and carboxylate oxygen atoms and participate in the construction of the three-dimensional framework. In 2, the in situ generated [Zn(bpy)(H(2)O)(4)](2+) cation acts as a template, which directs the ABW-type open-framework by strong hydrogen bonds. It is the first example where a metal complex is used as a template in the synthesis of metal phosphonates. The luminescent properties of 1 and 2 are also investigated. PMID- 22314306 TI - Report of the 39th SNACC Annual Meeting. PMID- 22314307 TI - Opioid receptor blockade prevents propofol-induced hypotension in rats. AB - BACKGROUND: Propofol is an intravenous anesthetic that is widely used to anesthetize patients during neurosurgical procedures. Although propofol is considered to be an essential component of contemporary management of acute brain injury in the operating room and in critical care settings, propofol-induced hypotension (PIH) remains a frequent and undesirable side effect. After 3 decades of clinical use, multiple proposed causes of PIH, and conflicting experimental results, the mechanism of PIH is still a puzzle for neuroscience and anesthesiology. This study evaluated the role of opioid receptors in PIH. METHODS: Pentobarbital-anesthetized rats were subjected to systemic or central pretreatment with naloxone followed by intravenous or central administration of propofol. RESULTS: In the absence of pretreatment with naloxone, intravenous (7.5 mg/kg) and intracistenal propofol (10 ug) injection induced 45% and 35% reductions in the mean arterial pressure, respectively (P<0.05). Both systemic (5 mg/kg) and central (100 ug) pretreatment with naloxone prevented PIH without independently affecting mean arterial pressure. CONCLUSIONS: This experiment in anesthetized rats indicates that central and peripheral opioid receptor blockade prevents PIH, suggesting that these receptors are involved in the cardiovascular alterations elicited by propofol administration. PMID- 22314308 TI - Neutralizing activity of immunoglobulin preparations. PMID- 22314310 TI - Vascular reconstruction using allogeneic homografts in a renal transplant patient with pseudoaneurysm and infected vascular prosthesis. PMID- 22314311 TI - Emergent renal revascularization of a simultaneous pancreas-kidney transplant recipient. PMID- 22314312 TI - Size evolution and surface characterization of solid-state nanopores in different aqueous solutions. AB - The stability and surface evolution of solid-state nanopores in aqueous solutions are extremely important since they would get immersed in solutions during DNA translocation experiment for DNA analyses. In this work, we systematically studied the size evolution of SiN nanopores in ethanol, deionized water and potassium chloride (KCl) solutions by careful surface characterization and composition analyses using a transmission electron microscope. Surprisingly, we found that nanopores closed up completely in ethanol in an hour and showed a 30% and 20% size decrease in deionized water and KCl solutions, respectively. Strong evidence of surface oxidation was found by composition analyses in the nanopore area. Nanopore size evolution was strongly dependent on initial pore size and solution pH value. In pH = 13 KCl solution, SiN nanopores were observed to increase in size instead of decrease. The results not only provide useful information for DNA detection based on solid-state nanopores, but can also guide design and application of other nanodevices exposed to electrolyte-solvent systems such as cell-on-a-chip devices and biosensors. PMID- 22314313 TI - Apolar carbohydrates as DNA capping agents. AB - Mono- and disaccharides have been shown to stack on top of DNA duplexes stabilizing sequences with terminal C-G base pairs. Here we present an apolar version of glucose and cellobiose as new capping agents that stack on DNA increasing considerably its stability with respect to their natural polyhydroxylated mono- and disaccharide DNA conjugates. PMID- 22314314 TI - Role of gallium and silver from phosphate-based glasses on in vitro dual species oral biofilm models of Porphyromonas gingivalis and Streptococcus gordonii. AB - Phosphate-based glasses (PBGs) are excellent controlled delivery agents for antibacterial ions such as silver and gallium. The aim of this study was to assess the potential utility of novel PBGs combining both gallium and silver for use in periodontal therapy. To this end, an in vitro biofilm model with the putative periodontal pathogen, Porphyromonas gingivalis, and an initial colonizer, Streptococcus gordonii, was established. The effect of increasing calcium content in gallium-silver-doped PBG on the susceptibility of P. gingivalis was examined. A decrease in degradation rates (30.34, 25.19, 21.40 MUg mm(-2) h(-1)) with increasing PBG calciumcontent (10, 11, 12 mol.% respectively) was observed, correlating well with gallium and silver ion release and antimicrobial activity against planktonic P. gingivalis (approximately 5.4log(10) colony-forming units (CFU) reduction after 24h by the C10 glass compared with controls) and S. gordonii (total growth inhibition after 32h by C10, C11 and C12 glasses compared with controls). The most potent PBG (C10) was evaluated for its ability to inhibit the biofilm growth of P. gingivalis in a newly established constant-depth film fermentor model. The simultaneous release of silver and gallium from the glass reduced P. gingivalis biofilm growth with a maximum effect (1.92log(10) CFU reduction) after 168 h. Given the emergence of antibiotic resistant bacteria and dearth of new antibiotics in development, the glasses, especially C10, would offer effective alternatives to antibiotics or may complement current therapies through controlled, localized delivery of gallium and silver ions at infected sites in the oral cavity. PMID- 22314315 TI - Osteointegration of titanium implant is sensitive to specific nanostructure morphology. AB - An important aspect of orthopedic implant integration is the enhancement of functional activity of osteoblasts at the tissue-implant interface without any fibrous tissue intervention. Nanostructured implant surfaces are known to enhance osteoblast activity. Previously, we have reported a simple hydrothermal method for the fabrication of non-periodic nanostructures (nanoscaffold, nanoleaves and nanoneedles) on titanium implants showing good biocompatibility and a distinct osteoblast response in vitro in terms of osteoblast adhesion to the surface. In the present work, these nanostructures have been evaluated for their detailed in vitro cellular response as well as in vivo osteointegration. Our studies showed that a specific surface nanomorphology, viz. nanoleaves, which is a network of vertically aligned, non-periodic, leaf-like structures with thickness in the nanoscale, provided a distinct increase in osteoblast cell proliferation, alkaline phosphatase (ALP) activity and collagen synthesis compared to several other types of nanomorphology, such as nanotubes, nanoscaffold and nanoneedles (rods). Gene expression analysis of ALP, osteocalcin, collagen, decorin and Runx2 showed ~20- to 40-fold up-regulation on the leaf-like topography. Cytoskeletal arrangement studies on this substrate again revealed a unique response with favorable intracellular protein expressions of vinculin, FAK and src. In vivo osteointegration study over 12 weeks on rat model (Sprague-Dawley) showed early stage bone formation (60% bone contact by week 2 and ~85% by week 8, p<0.01) in the leaf-like nanopattern, without any inflammatory cytokine production. PMID- 22314316 TI - Combination of chronic stress and ovariectomy causes conditioned fear memory deficits and hippocampal cholinergic neuronal loss in mice. AB - We have recently found that the combination of ovariectomy (OVX) and chronic restraint stress (CS) causes hippocampal pyramidal cell loss and cognitive dysfunction in female rats and that estrogen replacement prevents the OVX/CS induced morphological and behavioral changes. In this study, to clarify the mechanisms underlying the OVX/CS-mediated memory impairment further, we examined the roles of cholinergic systems in the OVX/CS-induced memory impairment in mice. Female Slc:ICR strain mice were randomly divided into two groups: OVX and sham operated groups. Two weeks after the operation, the mice of each group were further assigned to CS (6 h/day) or non-stress group. Following the 3-week-stress period, all mice were subjected to contextual fear conditioning, and context- and tone-dependent memory tests were conducted 1 or 24 h after the conditioning. Overburden with 3 weeks of CS from 2 weeks after OVX impaired context- and tone dependent freezing and the OVX/CS caused significant Nissl-stained neuron-like cell loss in the hippocampal CA3 region, although OVX and CS alone did not cause such behavioral and histological changes. Replacement of 17beta-estradiol for 5 weeks after OVX suppressed OVX/CS-induced memory impairment and hippocampal Nissl positive cell loss. Furthermore, the OVX/CS mice exhibited a significant decrease in choline acetyltransferase in the hippocampus compared with other groups. The cholinesterase inhibitors donepezil and galantamine ameliorated OVX/CS-induced memory impairment. These data suggest that cholinergic dysfunction may be involved in the OVX/CS-induced conditioned fear memory impairment. Overall, our findings suggest that the OVX/CS mouse model is useful to study the mechanisms underlying estrogen loss-induced memory deficits. PMID- 22314317 TI - Geissoschizine methyl ether, an alkaloid in Uncaria hook, is a potent serotonin 1A receptor agonist and candidate for amelioration of aggressiveness and sociality by yokukansan. AB - Yokukansan (YKS), a traditional Japanese medicine, is composed of seven kinds of dried herbs. It is widely prescribed in clinical situation for treating psychiatric disorders such as aggressiveness in patients with dementia. We previously demonstrated that YKS and Uncaria hook (UH), which is a constituent herb of YKS, had a partial agonistic effect to 5-HT(1A) receptors in vitro. However, it has still been unclear whether this in vitro effect is reflected in in vivo, and what the active ingredients are. The purpose of the present study is to find the active ingredient in YKS and to demonstrate the effect in in vivo. In the present study, we first studied the effect of YKS and UH on aggressiveness and sociality in socially isolated mice. YKS and UH ameliorated the isolation induced increased aggressiveness and decreased sociality, and these ameliorative effects were counteracted by coadministration of 5-HT(1A) receptor antagonist WAY 100635, or disappeared by eliminating UH from YKS. These results suggest that the effect of YKS is mainly attributed to UH, and the active ingredient is contained in UH. To find the candidate ingredients, we examined competitive binding assay and [(35)S] guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) binding assay of seven major alkaloids in UH using Chinese hamster ovary cells expressing 5-HT(1A) receptors artificially. Only geissoschizine methyl ether (GM) among seven alkaloids potently bound to 5-HT(1A) receptors and acted as a partial agonist. This in vitro result on GM was further demonstrated in the socially isolated mice. As did YKS and UH, GM ameliorated the isolation-induced increased aggressiveness and decreased sociality, and the effect was counteracted by coadministration of WAY-100635. These lines of results suggest that GM in UH is potent 5-HT(1A) receptor agonist and a candidate for pharmacological effect of YKS on aggressiveness and sociality in socially isolated mice. PMID- 22314318 TI - Effect of medroxyprogesterone on development of pentylenetetrazole-induced kindling in mice. AB - In the present study, the effect of medroxyprogesterone (MPA) is evaluated for its effect on pentylenetetrazole (PTZ) kindling model of epileptogenesis in mice followed by evaluation on kindling-induced changes in cognitive and motor functions. To explore whether the effects are mediated via progesterone receptors, a selective antagonist of progesterone (mifepristone, MIF) was also taken. Kindling was induced by once every 2 days treatment with PTZ (25 mg/kg, i.p.) for 5 weeks. The seizure severity during induction of kindling and % incidence of animals kindled at the end of 5 weeks were recorded. The motor function was assessed using a grip strength meter, whereas spatial memory was assessed in a cross maze. MPA (5 and 10 mg/kg, i.p.) significantly reduced the seizure severity scores and produced a significant decrease in the incidence of animals kindled at the end of 5 weeks (P<0.01). A higher efficacy was observed against male mice as compared with females following MPA. MIF neither reduced nor delayed the development of PTZ-induced kindling in mice. Also, it couldn't reverse the antiepileptogenic effects of MPA. On grip strength test (GST) and spontaneous alternation behavior (SAB), a significant decline in GST and % alternation was observed in kindled mice which was reversed by pre-treatment with MPA. MIF, however, could reverse only the reduced % alternation and not grip strength (GS) in PTZ-kindled animals. The study shows that MPA has antiepileptogenic effects against development of PTZ-induced kindling in mice that may not be mediated via progesterone receptors. PMID- 22314319 TI - Reduced Chrna7 expression in mice is associated with decreases in hippocampal markers of inhibitory function: implications for neuropsychiatric diseases. AB - The alpha7* nicotinic acetylcholine receptor encoded by CHRNA7 (human)/Chrna7 (mice) regulates the release of both the inhibitory neurotransmitter GABA and the excitatory neurotransmitter glutamate in the hippocampal formation. A heterozygous (Het) deletion at 15q13.3 containing CHRNA7 is associated with increased risk for schizophrenia, autism, and epilepsy. Each of these diseases are characterized by abnormalities in excitatory and inhibitory hippocampal circuit function. Reduced Chrna7 expression results in decreased hippocampal alpha7* receptor density, abnormal hippocampal auditory sensory processing, and increased hippocampal CA3 pyramidal neuron activity in C3H mice Het for a null mutation in Chrna7. These abnormalities demonstrate that decreased Chrna7 expression alters hippocampal inhibitory circuit function. The current study examined the specific impact of reduced Chrna7 expression on hippocampal inhibitory circuits by measuring the levels of GABA, GABA(A) receptors, the GABA synthetic enzyme l-glutamic acid decarboxylase-65 (GAD-65), and the vesicular GABA transporter 1 (GAT-1) in wild-type (Chrna7 +/+) and Het (Chrna7 +/-) C3H alpha7 mice of both genders. GAD-65 levels were significantly decreased in male and female Het C3H alpha7 mice, whereas GABA(A) receptors were significantly reduced only in male Het C3H alpha7 mice. No changes in GABA and GAT-1 levels were detected. These data suggest that reduced CHRNA7 expression may contribute to the abnormalities in hippocampal inhibitory circuits observed in schizophrenia, autism, and/or epilepsy. PMID- 22314320 TI - Functional similarity in relation to the external environment between circadian behavioral and melatonin rhythms in the subtropical Indian weaver bird. AB - The present study investigated whether the circadian oscillators controlling rhythms in activity behavior and melatonin secretion shared similar functional relationship with the external environment. We simultaneously measured the effects of varying illuminations on rhythms of movement and melatonin levels in Indian weaver birds under synchronized (experiment 1) and freerunning (experiment 2) light conditions. In experiment 1, weaverbirds were exposed to 12h light: 12h darkness (12L:12D; L = 20 lx, D = 0.1 lx) for 2.5 weeks. Then, the illumination of the dark period was sequentially enhanced to 1-, 5-, 10-, 20- and 100 lx at the intervals of about 2 to 4 weeks. In experiment 2, weaver birds similarly exposed for 2.5 weeks to 12L:12D (L = 100 lx; D = 0.1 lx) were released in constant dim light (LL(dim), 0.1 lx) for 6 weeks. Thereafter, LL(dim) illumination was sequentially enhanced to 1-, 3- and 5 lx at the intervals of about 2 weeks. Whereas the activity of singly housed individuals was continuously recorded, the plasma melatonin levels were measured at two time of the day, once in each light condition. The circadian outputs in activity and melatonin were phase coupled with an inverse phase relationship: melatonin levels were low during the active phase (light period) and high during the inactive phase (dark period). This phase relationship continued in both the synchronized and freerunning states as long as circadian activity and melatonin oscillators subjectively interpreted synchronously the daily light environment, based on illumination intensity and/or photophase contrast, as the times of day and night. There were dissociations between the response of the activity rhythms and melatonin rhythms in light conditions when the contrast between day and night was much reduced (20:10 lx) or became equal. We suggest that circadian oscillators governing activity behavior and melatonin secretion in weaverbirds are phase coupled, but they seem to independently respond to environmental cues. This would probably explain the varying degree to which the involvement of pineal/melatonin in regulation of circadian behaviors has been found among different birds. PMID- 22314321 TI - DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes. AB - Recurrent chromosomal translocations underlie both haematopoietic and solid tumours. Their origin has been ascribed to selection of random rearrangements, targeted DNA damage, or frequent nuclear interactions between translocation partners; however, the relative contribution of each of these elements has not been measured directly or on a large scale. Here we examine the role of nuclear architecture and frequency of DNA damage in the genesis of chromosomal translocations by measuring these parameters simultaneously in cultured mouse B lymphocytes. In the absence of recurrent DNA damage, translocations between Igh or Myc and all other genes are directly related to their contact frequency. Conversely, translocations associated with recurrent site-directed DNA damage are proportional to the rate of DNA break formation, as measured by replication protein A accumulation at the site of damage. Thus, non-targeted rearrangements reflect nuclear organization whereas DNA break formation governs the location and frequency of recurrent translocations, including those driving B-cell malignancies. PMID- 22314322 TI - Beyond morphology: minimal residual disease detection in acute myeloid leukemia. AB - PURPOSE OF REVIEW: Improved laboratory diagnostics over the past decade has resulted in identifiable genetic alterations and/or abnormal expression patterns in the majority of acute myeloid leukemia (AML). These leukemic patterns can then be monitored once patients achieve a morphologic remission. The role of various methodologies to detect minimal residual disease (MRD) in AML is reviewed, as well as the emerging role of MRD detection in prognostication and treatment decisions. RECENT FINDINGS: Assessment of MRD in AML is now possible using updated methods including real-time quantitative PCR (RQ-PCR) for abnormal fusion transcripts, RQ-PCR for proteins known to be overexpressed in AML such as Wilms' tumor gene, and multiparameter flow cytometry to detect leukemia-associated phenotypes. Using these techniques, MRD analysis has shown value in terms of risk assessment, continued patient monitoring, and for therapeutic decision-making. SUMMARY: MRD assessment can detect residual leukemia burden after treatment with improved sensitivity compared to morphology alone. There are now extensive data to support the prognostic value of MRD detection both after chemotherapy and in the pre and posttransplant setting, and emerging evidence to suggest there is a clinically relevant value to treatment decisions based on MRD results. The need for standardization of MRD technologies and interpretation is, thus, of critical importance. PMID- 22314323 TI - Current world literature. PMID- 22314325 TI - Plant stress surveillance monitored by ABA and disease signaling interactions. AB - Abiotic and biotic stresses are the major factors that negatively impact plant growth. In response to abiotic environmental stresses such as drought, plants generate resistance responses through abscisic acid (ABA) signal transduction. In addition to the major role of ABA in abiotic stress signaling, ABA signaling was reported to downregulate biotic stress signaling. Conversely recent findings provide evidence that initial activation of plant immune signaling inhibits subsequent ABA signal transduction. Stimulation of effector-triggered disease response can interfere with ABA signal transduction via modulation of internal calcium-dependent signaling pathways. This review overviews the interactions of abiotic and biotic stress signal transduction and the mechanism through which stress surveillance system operates to generate the most efficient resistant traits against various stress condition. PMID- 22314326 TI - Molecular characterization of a large MYBPC3 rearrangement in a cohort of 100 unrelated patients with hypertrophic cardiomyopathy. AB - Hypertrophic cardiomyopathy (HCM), a common and clinically heterogeneous disease characterized by unexplained ventricular myocardial hypertrophy and a high risk of sudden cardiac death, is mostly caused by mutations in MYH7 and MYBPC3 genes. As 70% of MYBPC3 mutations introduce a premature termination codon, the purpose of the current study was to report the prevalence of large MYBPC3 rearrangements. A large French cohort of 100 HCM patients, for whom no putatively causative point mutations were identified previously in the most prevalent HCM-causing genes, was investigated using an MLPA methodology. One HCM patient was identified to carry a large MYBPC3 rearrangement (<1%). This patient presents a 3505-bp deletion, which begins in the intron 27 and ends 485 bp after the MYBPC3 stop codon (g.47309385_47312889del). It was originated by recombination of a 296 bp AluSz sequence located in intron 27 and a 300 bp AluSx sequence located immediately downstream of exon 35. This study allowed the characterization of the first large MYBPC3 deletion reported in the literature. However, it appears that MLPA strategy, that moderates the identification of large MYBPC3 rearrangements, might confirm a clinical diagnosis only in a small number of patients (<1%). PMID- 22314327 TI - The albumin and monoclonal protein ratio as prognostic marker for multiple myeloma in the era of novel agents. AB - Multiple myeloma (MM) is a heterogeneous disease group regarding prognosis, clinical course, and response to therapeutic interventions. Numerous prognostic factors have been identified however there was no consensus about the best prognostic indicators or the proper staging systems. In a previous study the A/M ratio containing albumin (A) and monoclonal component (M) emerged as reliable predictor of survival duration in patients treated with conventional chemotherapy. In the current retrospective study authors evaluated the prognostic role of this fraction in the era of novel agents. They assessed the A/M ratio prior treatment in 56 newly diagnosed MM patients from the aspect of the survival time. According to the results the A/M being <1 at the diagnosis indicated significantly poorer prognosis both at the 2 years (p = 0,01) and at the 5 years (p = 0,07) survival endpoints. These results proved that A/M ratio remained valuable marker for predicting prognosis in patients treated with proteosome inhibitor and antiangiogenic therapy as well. Authors recommend therefore applying this A/M ratio in further studies for the better pre-treatment stratification. PMID- 22314328 TI - Differentiation of biologic scaffold materials through physicomechanical, thermal, and enzymatic degradation techniques. AB - OBJECTIVE: The objective of this study was to characterize the physicomechanical, thermal, and degradation properties of several types of biologic scaffold materials to differentiate between the various materials. BACKGROUND: As more biologic scaffold materials arrive on the market, it is critical that surgeons understand the properties of each material and are provided with resources to determine the suitability of these products for specific applications such as hernia repair. METHODS: Twelve biologic scaffold materials were evaluated, including crosslinked and non-crosslinked; those of bovine, human, and porcine origin; and derivatives of pericardium, dermis, and small intestine submucosa. Physicomechanical, thermal, and degradation properties were evaluated through biomechanical testing, modulated differential scanning calorimetry, and collagenase digestion assays, respectively. Biomechanical testing included suture retention, tear strength, uniaxial tensile, and ball burst techniques. RESULTS: All scaffolds exhibited suture retention strengths greater than 20 N, but only half of the scaffolds exhibited tear resistance greater than 20 N, indicating that some scaffolds may not provide adequate resistance to tearing. A wide range of burst strengths were observed ranging from 66.2 +/- 10.8 N/cm for Permacol to 1,028.0 +/- 199.1 N/cm for X-Thick AlloDerm, and all scaffolds except SurgiMend, Strattice, and CollaMend exhibited strains in the physiological range of 10% to 30% (at a stress of 16 N/cm). Thermal analysis revealed differences between crosslinked and non-crosslinked materials with crosslinked bovine pericardium and porcine dermis materials exhibiting a higher melting temperature than their non crosslinked counterparts. Similarly, the collagenase digestion assay revealed that crosslinked bovine pericardium materials resisted enzymatic degradation significantly longer than non-crosslinked bovine pericardium. CONCLUSIONS: Although differences were observed because of cross-linking, some crosslinked and non-crosslinked materials exhibited very similar properties. Variables other than cross-linking, such as decellularization/sterilization treatments or species/tissue type also contribute to the properties of the scaffolds. PMID- 22314329 TI - Predictive factors for the benefit of perioperative FOLFOX for resectable liver metastasis in colorectal cancer patients (EORTC Intergroup Trial 40983). AB - OBJECTIVE: In EORTC study 40983, perioperative FOLFOX increased progression-free survival (PFS) compared with surgery alone for patients with initially 1 to 4 resectable liver metastases from colorectal cancer (CRC). We conducted an exploratory retrospective analysis to identify baseline factors possibly predictive for a benefit of perioperative FOLFOX on PFS. METHODS: The analysis was based on 237 events from 342 eligible patients. Cox proportional hazards regression models with a significance level of 0.1 were used to build up univariate and multivariate models. RESULTS: After adjustment for identified prognostic factors, moderately (5.1-30 ng/mL) and highly (>30 ng/mL) elevated carcinoembryonic antigen (CEA) serum levels were both predictive for the benefit of perioperative chemotherapy (interaction P = 0.07; hazard ratio [HR] = 0.58 and HR = 0.52 for treatment benefit). For patients with moderately or highly elevated CEA (>5 ng/mL), the 3-year PFS was 35% with perioperative chemotherapy compared to 20% with surgery alone. Performance status (PS) 0 and BMI lower than 30 were also predictive for the benefit of perioperative chemotherapy (interaction P = 0.04 and P = 0.02). However, the number of patients with PS 1 and BMI 30 or higher were limited. The benefit of perioperative therapy was not influenced by the number of metastatic lesions (1 vs 2-4, interaction HR = 0.98). CONCLUSIONS: Perioperative FOLFOX seems to benefit in particular patients with resectable liver metastases from CRC when CEA is elevated and when PS is unaffected, regardless of the number of metastatic lesions.ClinicalTrials.gov number NCT00006479. PMID- 22314330 TI - Prehospital intravenous fluid administration is associated with higher mortality in trauma patients. PMID- 22314331 TI - Geometric phase and gauge connection in polyatomic molecules. AB - Geometric phase is an interesting topic that is germane to numerous and varied research areas: molecules, optics, quantum computing, quantum Hall effect, graphene, and so on. It exists only when the system of interest interacts with something it perceives as exterior. An isolated system cannot display geometric phase. This article addresses geometric phase in polyatomic molecules from a gauge field theory perspective. Gauge field theory was introduced in electrodynamics by Fock and examined assiduously by Weyl. It yields the gauge field A(MU), particle-field couplings, and the Aharonov-Bohm phase, while Yang Mills theory, the cornerstone of the standard model of physics, is a template for non-Abelian gauge symmetries. Electronic structure theory, including nonadiabaticity, is a non-Abelian gauge field theory with matrix-valued covariant derivative. Because the wave function of an isolated molecule must be single valued, its global U(1) symmetry cannot be gauged, i.e., products of nuclear and electron functions such as chi(n)psi(n) are forbidden from undergoing local phase transformation on R, where R denotes nuclear degrees of freedom. On the other hand, the synchronous transformations (first noted by Mead and Truhlar): psi(n) >psi(n)e(izeta) and simultaneously chi(n)->chi(n)e(-izeta), preserve single valuedness and enable wave functions in each subspace to undergo phase transformation on R. Thus, each subspace is compatible with a U(1) gauge field theory. The central mathematical object is Berry's adiabatic connection i, which serves as a communication link between the two subsystems. It is shown that additions to the connection according to the gauge principle are, in fact, manifestations of the synchronous (e(izeta)/e(-izeta)) nature of the psi(n) and chi(n) phase transformations. Two important U(1) connections are reviewed: qA(MU) from electrodynamics and Berry's connection. The gauging of SU(2) and SU(3) is reviewed and then used with molecules. The largest gauge group applicable in the immediate vicinity of a two-state intersection is U(2), which factors to U(1) * SU(2). Gauging SU(2) yields three fields, whereas U(1) is not gauged, as the result cannot be brought into registry with electronic structure theory, and there are other problems as well. A parallel with spontaneous symmetry breaking in electroweak theory is noted. Loss of SU(2) symmetry as the energy gap between adiabats increases yields the inter-related U(1) symmetries of the upper and lower adiabats, with spinor character imprinted in the vicinity of the degeneracy. PMID- 22314332 TI - Postnatal low protein diet programs leptin signaling in the hypothalamic pituitary-thyroid axis and pituitary TSH response to leptin in adult male rats. AB - Maternal protein restriction (PR) during lactation programs a lower body weight, hyperthyroidism, leptin resistance, and over-expression of leptin receptor in the pituitary gland at adulthood. Because leptin regulates energy homeo-stasis and the hypothalamus-pituitary-thyroid (HPT) axis, we evaluated adipocyte morphology, the leptin signaling pathway in the HPT axis and the in vitro thyrotropin (TSH) response to leptin in adult progeny in this model. At birth, dams were separated in control diet with 23% protein or PR diet with 8% protein. After weaning, offspring received a normal diet. Adult PR offspring showed lower adipocytes area, higher leptin:visceral fat ratio, lower hypothalamic signal transducer and activator of transcription 3 (STAT3), higher pituitary leptin receptor (Ob-R) and lower thyroid janus tyrosine kinase 2 (JAK2) contents. Regarding the in vitro study, 10(-7) M leptin stimulated TSH secretion in C offspring at 30 min, but had no effect in PR offspring. At 120 min, 10(-7) M leptin decreased TSH secretion in C offspring and increased in PR offspring. Maternal nutritional status during lactation programs for adipocyte atrophy, higher relative leptin secretion and changes in the downstream leptin signaling in the HPT axis and the TSH response to leptin, suggesting a role for leptin in the development of the HPT axis and helping to explain thyroid dysfunction and leptin resistance in this programming model. Because leptin stimulates thyroid function, it is unlikely that these alterations were responsible for the increased in serum T4 and T3. Therefore, neonatal PR programs a hyperthyroidism, lower adipogenesis, and impairment of leptin action. PMID- 22314333 TI - Maternal prolactin inhibition during lactation affects physical performance evaluated by acute exhaustive swimming exercise in adult rat offspring. AB - Maternal prolactin inhibition at the end of lactation programs for metabolic syndrome and hypothyroidism in adult offspring, which could negatively affect exercise performance. We evaluated the effects of maternal hypoprolactinemia in late lactation on physical performance in adult progeny. Lactating Wistar rats were treated with bromocriptine (BRO, 1 mg per day) or saline on days 19, 20, and 21 of lactation and offspring were followed until 180 days old. Physical performance was recorded in untrained rats at 90 and 180 days by an acute exhaustive swimming test (exercise group-Ex). At day 90, BRO offspring showed higher visceral fat mass, higher plasma thiobarbituric acid reactive substances, lower total antioxidant capacity, higher liver glycogen, lower glycemia, and normal insulinemia. Although thyroid hormones (TH) levels were unchanged, mitochondrial glycerol phosphate dehydrogenase (mGPD) activity was lower in muscle and in brown adipose tissue (BAT). At this age, BRO-Ex offspring showed higher exercise capacity, lower blood lactate, higher serum T3, and higher muscle and BAT mGPD activities. At day 180, BRO offspring showed central obesity, hypothyroidism, insulin resistance, and lower EDL (extensor digitorum longus) muscle glycogen with unaltered plasma oxidative stress markers. This group showed no alteration of exercise capacity or blood lactate. After exercise, EDL and liver glycogen were lower, while T3 levels, BAT and muscle mGPD activities were normalized. Liver glycogen seem to be related with higher exercise capacity in younger BRO offspring, while the loss of this temporary advantage maybe related to the hypothyroidism and insulin resistance developed with age. PMID- 22314334 TI - Visfatin levels in prepubertal children born small or large for gestational age. AB - Children born small (SGA) or large (LGA) for gestational age are prone to develop insulin resistance (IR) during childhood. Visfatin, a hormone with insulin mimetic actions, has been associated with IR. This study was designed to examine whether serum level of visfatin is correlated with metabolic indices of IR, in prepuberty in association with the intrauterine growth pattern. The following parameters were evaluated at a mean age of 6.5+/-1.2 years in 155 prepubertal children born appropriate for the gestational age (AGA) (n=63), or SGA (n=42), or LGA (n=50): serum levels of visfatin, adiponectin, leptin, fasting glucose (G(F)) and insulin (I(F)), the homeostasis model assessment IR index (HOMA-IR), plasma lipids, anthropometric indices at birth and the time of evaluation, and obesity indices [waist circumference (WC), body mass index (BMI) and skinfold thickness]. The mean serum level of visfatin was lower in the SGA than in the AGA and the LGA children (9+/-5.2 vs. 11.8+/-5.1 and 12.7+/-5.6 ng/ml, respectively, p<0.01). Girls had lower visfatin levels than boys (10.4+/-4.3 ng/ml vs. 12.5+/-6.7 ng/ml, p<0.05). Visfatin was not correlated with IR indices. In multiple regression analysis visfatin level was positively correlated with birth weight z-score (t=2.56, beta=0.24, p<0.01) and crown to heel z-score (t=2.46, beta=0.22, p=0.014), independent of age, gender, maternal weight before pregnancy, maternal weight gain during pregnancy, BMI z-score, WC z-score, serum leptin and adiponectin, and HOMA-IR. In conclusion serum visfatin level was lower in prepubertal SGA children but not correlated with IR indices. Low birth weight was an independent predictor of visfatin level. PMID- 22314336 TI - Super reduced Fe4S4 cluster of Balch's dithiolene series. AB - A super reduced Fe(4)S(4) cluster with a sulfur based radical, [NBu(4)](4)[Fe(3)(III)Fe(II)(MU(3)-S)(4)(mnt)(3)(6-)(mnt)(1-)](4-), (1) (mnt, maleonitrile dithiolate) which evolves H(2)S gas on treatment with acid under ambient conditions has been synthesized and structurally characterized. The Fe-S distances in 1 are in the range 2.246-2.383 A, in stark contrast to that of the known n = -2 member of the series based on the [Fe(4)(MU(3) S)(4)(S(2)C(2)R(2))(4)](n) unit (R = CF(3), Ph) with Fe-S bond lengths of 2.149 2.186 A. The EPR of 1 displays very weak signals at g, 4.03 and 2.38 along with a strong S-based radical EPR signal at g, 2.003 associated with five structured components tentatively assigned to hyperfine interaction arising out of the naturally abundant (57)Fe with = 88 G. The EPR profile resembles the reduced Fe-S cluster of CO inhibited Clostridium pasteurianum W5 hydrogenase or the Fe(4)S(4) centers of wild-type enzyme, IspH treated with HMBPP or IPP. PMID- 22314337 TI - Clonal evolution including partial loss of human leukocyte antigen genes favoring extramedullary acute myeloid leukemia relapse after matched related allogeneic hematopoietic stem cell transplantation. AB - BACKGROUND: Relapse of acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT) leaves few therapeutic options, and mechanisms of immune escape of recurring leukemic cells remain poorly understood. Recently, acquired loss of mismatched human leukocyte antigen (HLA) was demonstrated in patients with AML undergoing haploidentical allogeneic HSCT and was suggested not to occur in HLA-matched HSCT. We hypothesized that this mechanism applies to extramedullary AML relapse which occurs frequently after allogeneic HSCT and might also not be restricted to haploidentical HSCT. METHODS: DNA from extramedullary AML relapse after HSCT was compared with bone marrow at diagnosis with array comparative genomic hybridization to investigate relapse specific genomic aberrations in relapsing AML after allogeneic HSCT. Formalin fixed, paraffin-embedded tissues from the same points of time were assessed for HLA, major histocompatibility complex class I chain-related gene A, and TAP2 immunohistochemistry staining to assess cell surface expression of deleted loci encoded on chromosome 6p. RESULTS: Array comparative genomic hybridization revealed a partial loss of chromosome 6p in extramedullary myeloid sarcoma relapse of AML after sustained complete remission was achieved through matched related allogeneic HSCT. Among others, a deleted region 6p21.32-p21.33, which included several HLA class I genes, was detected. CONCLUSIONS: These results suggest that the loss of HLA class I haplotype also occurs in AML relapse after HLA-matched related HSCT. Partial loss of several HLA class I genes and subsequent reduced presentation of minor histocompatibility antigens and reduced ligation of activating natural killer-cell receptors may explain the loss of graft-versus-leukemia response and extramedullary AML relapse in tissue with reduced immunologic surveillance. PMID- 22314338 TI - Diagnostic utility of human cytomegalovirus-specific T-cell response monitoring in predicting viremia in pediatric allogeneic stem-cell transplant patients. AB - BACKGROUND: Several studies proved that virus-specific T-cells play a pivotal role in controlling cytomegalovirus (CMV) infection in adult allogeneic hematopoietic stem-cell transplant (HSCT) patients. Fewer data are available in pediatric HSCT settings, when immature and inexperienced immune system may affect antiviral immune reconstitution. METHODS: We analyzed prospectively the CMV specific T-cell reconstitution in a cohort of 31 pediatric allogeneic HSCT recipients at 30, 60, 90, 120, 180, and 360 days after HSCT. RESULTS: Depending on donor-recipient CMV serostatus, we observed distinct patterns and kinetics of CMV-specific T-cell immune reconstitution: during the early time-points, patients displayed a severe reduction in CMV-specific T-cell recovery in both CMV seropositive donor (D+) group and CMV seronegative donor (D-) on CMV seropositive recipients (R+). From day 90 onward, statistical significant differences in the profile of T-cell immune reconstitution emerged between D+ and D-. The pattern of immune reconstitution was characterized by heterogeneous kinetics and efficiencies: we report cases of: (1) spontaneous antiviral T-cell recovery with no previous viremia, (2) immune T-cell recovery anticipated by CMV viremia, and (3) no T-cell immune reconstitution despite previous viremia episodes. CONCLUSIONS: Given the heterogeneous scenarios of antiviral T-cell immune recovery in pediatric allogeneic HSCT, we conclude that the evaluation of the antiviral immune reconstitution is a promising and appealing system for identifying patients at higher risk of CMV infection. The use of interferon-gamma ELISPOT test is a valid tool for immunological monitoring and predicting CMV viremia in pediatric HSCT. PMID- 22314340 TI - Evidence for a reactive (alkene)peroxoiridium(III) intermediate in the oxidation of an alkene complex with O2. AB - An (alkene)peroxoiridium(III) complex, [Ir(L)(cod)(O(2))] [where LH = PhN=C(NMe(2))NHPh and cod = 1,5-cyclooctadiene], was identified as an intermediate in the reaction of the Ir(I) precursor [Ir(L)(cod)] with O(2) and characterized by spectroscopic methods. Decay of the intermediate and further reaction with 1,5-cyclooctadiene produced 4-cycloocten-1-one. PMID- 22314339 TI - Long-term (5 years) efficacy and safety of pancreas transplantation alone in type 1 diabetic patients. AB - BACKGROUND: Although combined pancreas and kidney transplantation is an established procedure for the treatment of type 1 diabetes (T1D) in patients with end-stage renal disease, the role of pancreas transplant alone (PTA) in the therapy of T1D subjects with preserved kidney function is still matter of debate. METHODS: We report our single-center experience of PTA in 71 consecutive T1D patients all with a posttransplant follow-up of 5 years. Patient and pancreas (normoglycemia in the absence of any antidiabetic therapy) survivals were determined, and several clinical parameters (including risk factors for cardiovascular diseases) were assessed. Cardiac evaluation and Doppler echocardiographic examination were also performed, and renal function and proteinuria were evaluated. RESULTS: Actual patient and pancreas survivals at 5 years were 98.6% and 73.2%, respectively. Relaparotomy was needed in 18.3% of cases. Restoration of endogenous insulin secretion was accompanied by sustained normalization of fasting plasma glucose concentrations and HbA1c levels as well as significant improvement of total cholesterol, low-density lipoprotein cholesterol, and blood pressure. An improvement of left ventricular ejection fraction was also observed. Proteinuria (24 hours) decreased significantly after transplantation. One patient developed end-stage renal disease. In the 51 patients with sustained pancreas graft function, kidney function (serum creatinine and glomerular filtration rate) decreased over time with a slower decline in recipients with pretransplant glomerular filtration rate less than 90 mL/min. CONCLUSIONS: PTA was an effective and reasonably safe procedure in this single-center cohort of T1D patients. PMID- 22314341 TI - Biological activity of Fe(III) aquo-complexes towards ferric chelate reductase (FCR). AB - In this study we have obtained experimental evidence that confirms the high activity of aquo complexes III and IV towards the enzyme FCR, responsible for the reduction of Fe(III) to Fe(II) in the process of iron acquisition by plants. The in vivo FCR assays in roots of stressed cucumber plants have shown a higher efficiency of the family of complexes III and a striking structure-activity relationship with the nature of the substituent placed in a phenyl group far away from the metal center. The results obtained in this work demonstrate that all the aquo compounds tested interact efficiently with the enzyme FCR and hence constitute a new concept of iron chelates that could be of great use in agronomy. PMID- 22314345 TI - Utility of clot formation and lysis assay to monitor global coagulation state of patients with severe acute pancreatitis. AB - BACKGROUND: Systemic inflammation affects hemostasis during severe acute pancreatitis (SAP). A hypercoagulable state occurs more frequently in SAP, which is not fully detected by traditional coagulation testing. AIMS: The aim of this study was to evaluate the contribution of clot formation and lysis (CloFAL) assay to improve monitoring of global coagulation in patients with SAP. METHODS: Twenty five patients with SAP who were treated from December 2009 to April 2011 were studied. Plasma was collected at the time of admission, and CloFAL was measured using the CloFAL analyzer. The parameters evaluated include coagulation time (CT), fibrinolysis time (FT), and maximum amplitude (MA), from which the accelerating coagulation extent (ACE, MA/CT), accelerating fibrinolytic extent (AFE, MA/FT), and balance level exponent (BLE, ACE/AFE) were calculated. In addition, laboratory values for the traditional coagulation testing were measured. Values were compared to a control group of 20 healthy subjects. RESULTS: The MA, FT, ACE, and BLE values of the CloFAL assay were significantly increased in the SAP group compared to the control group (p?0.05 for all measurements). For the traditional coagulation testing, fibrinogen, plasminogen, and D-dimer levels were higher in patients in the SAP group compared to the control group (p?0.05). CONCLUSIONS: Our findings using the CloFAL analyzer indicate that the hypercoagulable state was due to increased fibrin generation and invariable fibrinolysis in patients with SAP. CloFAL assay is a simple and useful global coagulation assay to monitor hypercoagulable states during SAP. PMID- 22314346 TI - Hepatic height on coronal computed tomography images predicts total liver volume in European adults without liver disease. AB - BACKGROUND: Hepatic volume measurement provides useful information in a large range of clinical situations. AIMS: The goal of this study was to test the hypothesis that significant correlation exists between hepatic volume calculated using three-dimensional reconstruction of computed tomography (CT) data and hepatic height calculated using coronal reformation of CT images in European adult patients without liver disease. METHODS: One hundred patients (50 men, 50 women; mean age, 47 years) without hepatic disease were included. Coronal and three-dimensional images of the liver were obtained using 64-section helical CT. Correlation between hepatic height and hepatic volume was searched for using the Pearson correlation test. Regression analysis was used to compare hepatic height and hepatic volume. RESULTS: A strong and highly significant positive correlation was found between hepatic height and hepatic volume, with a correlation coefficient (r) of 0.767 (95%CI 0.672-0.837; r2 = 0.588) (P < 0.001). The equation of the correlation line was y = 11.764x - 244 where y represents the hepatic volume in cm3 and x the hepatic height in mm. CONCLUSION: Hepatic height as obtained on coronal CT image is a simple and rapid measurement that allows predicting hepatic volume in European adult patients without liver disease. PMID- 22314347 TI - Superior photodecomposition of pyrene by metal ion-loaded TiO2 catalyst under UV light irradiation. AB - BACKGROUND: The photocatalytic degradation of pyrene under UV (125 W Hg-Arc, 10.4 mW/cm2) irradiation of TiO2 aqueous suspension has been found to be highly improved with the dissolved transition metal ions like Cu2+, Fe3+, Ag+, and Au3+, etc. As the reduction potential of these metals lies below the conduction band (CB) position (-0.1 eV) of TiO2, the photoexcited electron transfer occurs more readily and reduces electron-hole recombination rate. Therefore, it has a beneficial influence on the photocatalytic ability of TiO2 because of rapid Fermi energy equilibrium between the CB of TiO2 and its surface adsorbed metal ions. RESULTS AND DISCUSSION: The Fermi level is referred to as the electrochemical potential and plays an important role in the band theory of solids. When metal and semiconductor are in contact, electron migration from photoirradiated semiconductor to the deposited metal occurs at the interface until two Fermi levels equilibrate and enhanced the photocatalytic activity of semiconductor photocatalyst. Ni2+ having more negative reduction potential (-0.25 eV) than the CB of TiO2 imparts negligible co-catalytic activity to TiO2 photoreaction. It also revealed that loading of Au3+ ions displayed higher degradation rate of pyrene than Au photodeposition. Furthermore, when the amount of dissolved Fe+3 and Au3+ ions gradually increases from 0.1 to 2 wt.%, the pyrene photodecomposition rate also become faster. PMID- 22314348 TI - Major, minor and trace element content derived from aquacultural activity of marine sediments (Central Adriatic, Croatia). AB - INTRODUCTION AND PURPOSE: Studies examining the environmental impact of marine aquaculture have increased significantly in number during the last few decades. The present paper investigates a region of rapid growth in intensive aquaculture and its influence on the local marine ecosystem. DISCUSSION: This study was undertaken with the specific aim of assessing the effect of fish farming on marine sediment at a farm near the island of Vrgada in the Central Adriatic. Data obtained regarding major (Si, Al, K, Na, Fe, Ca, Mg), minor (Mn, P, Ti) and trace (As, Au, Ba, Cd, Co, Cr, Cs, Cu, Ga, Hf, Hg, Mo, Nb, Ni, Pb, Rb, Sb, Sc, Se, Sr, Ta, Th, Tl, U, V, Y, Zn, Zr) elements were used to estimate the spatial and temporal distribution of metals in the sediment and their possible relationship with local aquacultural activity. RESULTS: Although the measured concentrations of heavy metals in sediment below fish cages were notably different and potentially a result of farming activity, the values were generally lower than background concentrations observed in the Central Adriatic. In contrast, concentrations of heavy metals at a reference site unaffected by aquaculture varied from lower levels to values even higher than those observed below the high production cages. Furthermore, calculated environmental index values indicate that the sediment below the farm is either uncontaminated or suffers from only low levels of contamination. CONCLUSION: Such results suggest that the effect of observed fish farm activity on the local marine ecosystem is practically negligible. PMID- 22314349 TI - Salt marsh macrophyte Phragmites australis strategies assessment for its dominance in mercury-contaminated coastal lagoon (Ria de Aveiro, Portugal). AB - INTRODUCTION AND AIMS: The dominance of a plant species in highly metal contaminated areas reflects its tolerance or adaptability potential to these scenarios. Hence, plants with high adaptability and/or tolerance to exceptionally high metal-contaminated scenarios may help protect environmental degradation. The present study aimed to assess the strategies adopted by common reed, Phragmites australis for its dominance in highly mercury-contaminated Ria de Aveiro coastal lagoon (Portugal). MATERIALS AND METHODS: Both plant samples and the sediments vegetated by monospecific stand of Phragmites australis were collected in five replicates from mercury-free (reference) and contaminated sites during low tide between March 2006 and January 2007. The sediments' physico-chemical traits, plant dry mass, uptake, partitioning, and transfer of mercury were evaluated during growing season (spring, summer, autumn, and winter) of P. australis. Redox potential and pH of the sediment around roots were measured in situ using a WTW pH 330i meter. Dried sediments were incinerated for 4 h at 500 degrees C for the estimation of organic matter whereas plant samples were oven-dried at 60 degrees C till constant weight for plant dry mass determination. Mercury concentrations in sediments and plant parts were determined by atomic absorption spectrometry with thermal decomposition, using an advanced mercury analyzer (LECO 254) and maintaining the accuracy and precision of the analytical methodologies. In addition, mercury bioaccumulation and translocation factors were also determined to differentiate the accumulation of mercury and its subsequent translocation to plant parts in P. australis. RESULTS AND CONCLUSIONS: P. australis root exhibited the highest mercury accumulation followed by rhizome and leaves during the reproductive phase (autumn). During the same phase, P. australis exhibited ~5 times less mercury-translocation factor (0.03 in leaf) when compared with the highest mercury bioaccumulation factor for root (0.14). Moreover, seasonal variations differentially impacted the studied parameters. P. australis' extraordinary ability to (a) pool the maximum mercury in its roots and rhizomes, (b) protect its leaf against mercury toxicity by adopting the mercury exclusion, and (c) adjust the rhizosphere-sediment environment during the seasonal changes significantly helps to withstand the highly mercury-contaminated Ria de Aveiro lagoon. The current study implies that P. australis has enough potential to be used for mercury stabilization and restoration of sediments/soils rich in mercury as well. PMID- 22314350 TI - Modelling of bacterial growth with shifts in temperature using automated methods with Listeria monocytogenes and Pseudomonas aeruginosa as examples. AB - Time to detection (TTD) measurements using turbidometry allow a straightforward method for the measurement of bacterial growth rates under isothermal conditions. Growth rate measurements were carried out for Listeria monocytogenes at 25, 30 and 37 degrees C and for Pseudomonas aeruginosa over the temperature range 25 to 45 degrees C. The classical three-parameter logistic model was rearranged to provide the theoretical foundation for the observed TTD. A model was subsequently developed for the analysis of TTD data from non-isothermal studies based on the Malthusian approximation of the logistic model. The model was able to predict the TTD for cultures of L. monocytogenes or P. aeruginosa undergoing simple temperature shunts (e.g. 25 to 37 degrees C and vice versa), and for a multiple temperature shunt for L. monocytogenes (25-37-25-37 degrees C and 37-25-37-25 degrees C) over a period of 24h. In no case did a temperature shunt induce a lag. PMID- 22314351 TI - Neuroprotective effects of digested polyphenols from wild blackberry species. AB - PURPOSE: Blackberry ingestion has been demonstrated to attenuate brain degenerative processes with the benefits ascribed to the (poly)phenolic components. The aim of this work was to evaluate the neuroprotective potential of two wild blackberry species in a neurodegeneration cell model and compare them with a commercial variety. METHODS: This work encompasses chemical characterization before and after an in vitro digestion and the assessment of neuroprotection by digested metabolites. Some studies targeting redox/cell death systems were also performed to assess possible neuroprotective molecular mechanisms. RESULTS: The three blackberry extracts presented some quantitative differences in polyphenol composition that could be responsible for the different responses in the neurodegeneration cell model. Commercial blackberry extracts were ineffective but both wild blackberries, Rubus brigantinus and Rubus vagabundus, presented neuroprotective effects. It was verified that a diminishment of intracellular ROS levels, modulation of glutathione levels and activation of caspases occurred during treatment. The last effect suggests a preconditioning effect since caspase activation was not accompanied by diminution in cell death and loss of functionality. CONCLUSIONS: This is the first time that metabolites obtained from an in vitro digested food matrix, and tested at levels approaching the concentrations found in human plasma, have been described as inducing an adaptative response. PMID- 22314356 TI - Rapid microbial response to the presence of an ancient relic in the Antarctic Dry Valleys. AB - The extreme cold and aridity of the Antarctic McMurdo Dry Valleys have led to the longstanding belief that metabolic rates of soil microbiota are negligible, and that ecosystem changes take place over millennia. Here we report the first direct experimental evidence that soil microbial communities undergo rapid and lasting changes in response to contemporary environmental conditions. Mummified seals, curious natural artifacts found scattered throughout Dry Valleys, alter their underlying soil environment by stabilizing temperatures, elevating relative humidity and reducing ultraviolet exposure. In a unique, multi-year mummified seal transplantation experiment, we found that endemic Dry Valley microbial communities responded to these changes within 3 years, resulting in a sevenfold increase in CO(2) flux and a significant reduction in biodiversity. These findings challenge prevailing ideas about Antarctic Dry Valley ecosystems and indicate that current and future environmental conditions may strongly influence the ecology of the dominant biota in the Dry Valleys. PMID- 22314357 TI - Generation and control of polarization-entangled photons from GaAs island quantum dots by an electric field. AB - Semiconductor quantum dots are potential sources for generating polarization entangled photons efficiently. The main prerequisite for such generation based on biexciton-exciton cascaded emission is to control the exciton fine-structure splitting. Among various techniques investigated for this purpose, an electric field is a promising means to facilitate the integration into optoelectronic devices. Here we demonstrate the generation of polarization-entangled photons from single GaAs quantum dots by an electric field. In contrast to previous studies, which were limited to In(Ga)As quantum dots, GaAs island quantum dots formed by a thickness fluctuation were used because they exhibit a larger oscillator strength and emit light with a shorter wavelength. A forward voltage was applied to a Schottky diode to control the fine-structure splitting. We observed a decrease and suppression in the fine-structure splitting of the studied single quantum dot with the field, which enabled us to generate polarization-entangled photons with a high fidelity of 0.72 +/- 0.05. PMID- 22314358 TI - Imperfect interface of Beclin1 coiled-coil domain regulates homodimer and heterodimer formation with Atg14L and UVRAG. AB - Beclin 1 is a core component of the Class III Phosphatidylinositol 3-Kinase VPS34 complex. The coiled coil domain of Beclin 1 serves as an interaction platform for assembly of distinct Atg14L- and UVRAG-containing complexes to modulate VPS34 activity. Here we report the crystal structure of the coiled coil domain that forms an antiparallel dimer and is rendered metastable by a series of 'imperfect' a-d' pairings at its coiled coil interface. Atg14L and UVRAG promote the transition of metastable homodimeric Beclin 1 to heterodimeric Beclin1 Atg14L/UVRAG assembly. Beclin 1 mutants with their 'imperfect' a-d' pairings modified to enhance self-interaction, show distinctively altered interactions with Atg14L or UVRAG. These results suggest that specific utilization of the dimer interface and modulation of the homodimer-heterodimer transition by Beclin 1-interacting partners may underlie the molecular mechanism that controls the formation of various Beclin1-VPS34 subcomplexes to exert their effect on an array of VPS34-related activities, including autophagy. PMID- 22314359 TI - Emergent neutrality leads to multimodal species abundance distributions. AB - Recent analyses of data sampled in communities ranging from corals and fossil brachiopods to birds and phytoplankton suggest that their species abundance distributions have multiple modes, a pattern predicted by none of the existing theories. Here we show that the multimodal pattern is consistent with predictions from the theory of emergent neutrality. This adds to the observations, suggesting that natural communities may be shaped by the evolutionary emergence of groups of similar species that coexist in niches. Such self-organized similarity unifies niche and neutral theories of biodiversity. PMID- 22314360 TI - Broadband light management using low-Q whispering gallery modes in spherical nanoshells. AB - Light trapping across a wide band of frequencies is important for applications such as solar cells and photodetectors. Here, we demonstrate a new approach to light management by forming whispering-gallery resonant modes inside a spherical nanoshell structure. The geometry of the structure gives rise to a low quality factor, facilitating the coupling of light into the resonant modes and substantial enhancement of the light path in the active material, thus dramatically improving absorption. Using nanocrystalline silicon (nc-Si) as a model system, we observe broadband absorption enhancement across a large range of incident angles. The absorption of a single layer of 50-nm-thick spherical nanoshells is equivalent to a 1-MUm-thick planar nc-Si film. This light-trapping structure could enable the manufacturing of high-throughput ultra-thin film absorbers in a variety of material systems that demand shorter deposition time, less material usage and transferability to flexible substrates. PMID- 22314361 TI - Modification of the carboxy-terminal flanking region of a universal influenza epitope alters CD4+ T-cell repertoire selection. AB - Human CD4(+) alphabeta T cells are activated via T-cell receptor recognition of peptide epitopes presented by major histocompatibility complex (MHC) class II (MHC-II). The open ends of the MHC-II binding groove allow peptide epitopes to extend beyond a central nonamer core region at both the amino- and carboxy terminus. We have previously found that these non-bound C-terminal residues can alter T cell activation in an MHC allele-transcending fashion, although the mechanism for this effect remained unclear. Here we show that modification of the C-terminal peptide-flanking region of an influenza hemagglutinin (HA(305-320)) epitope can alter T-cell receptor binding affinity, T-cell activation and repertoire selection of influenza-specific CD4(+) T cells expanded from peripheral blood. These data provide the first demonstration that changes in the C-terminus of the peptide-flanking region can substantially alter T-cell receptor binding affinity, and indicate a mechanism through which peptide flanking residues could influence repertoire selection. PMID- 22314362 TI - Ultrafast heating as a sufficient stimulus for magnetization reversal in a ferrimagnet. AB - The question of how, and how fast, magnetization can be reversed is a topic of great practical interest for the manipulation and storage of magnetic information. It is generally accepted that magnetization reversal should be driven by a stimulus represented by time-non-invariant vectors such as a magnetic field, spin-polarized electric current, or cross-product of two oscillating electric fields. However, until now it has been generally assumed that heating alone, not represented as a vector at all, cannot result in a deterministic reversal of magnetization, although it may assist this process. Here we show numerically and demonstrate experimentally a novel mechanism of deterministic magnetization reversal in a ferrimagnet driven by an ultrafast heating of the medium resulting from the absorption of a sub-picosecond laser pulse without the presence of a magnetic field. PMID- 22314363 TI - EphB3 suppresses non-small-cell lung cancer metastasis via a PP2A/RACK1/Akt signalling complex. AB - Eph receptors are implicated in regulating the malignant progression of cancer. Here we find that despite overexpression of EphB3 in human non-small-cell lung cancer, as reported previously, the expression of its cognate ligands, either ephrin-B1 or ephrin-B2, is significantly downregulated, leading to reduced tyrosine phosphorylation of EphB3. Forced activation of EphB3 kinase in EphB3 overexpressing non-small-cell lung cancer cells inhibits cell migratory capability in vitro as well as metastatic seeding in vivo. Furthermore, we identify a novel EphB3-binding protein, the receptor for activated C-kinase 1, which mediates the assembly of a ternary signal complex comprising protein phosphatase 2A, Akt and itself in response to EphB3 activation, leading to reduced Akt phosphorylation and subsequent inhibition of cell migration. Our study reveals a novel tumour-suppressive signalling pathway associated with kinase-activated EphB3 in non-small-cell lung cancer, and provides a potential therapeutic strategy by activating EphB3 signalling, thus inhibiting tumour metastasis. PMID- 22314364 TI - Parkin controls dopamine utilization in human midbrain dopaminergic neurons derived from induced pluripotent stem cells. AB - Parkinson's disease (PD) is defined by the degeneration of nigral dopaminergic (DA) neurons and can be caused by monogenic mutations of genes such as parkin. The lack of phenotype in parkin knockout mice suggests that human nigral DA neurons have unique vulnerabilities. Here we generate induced pluripotent stem cells from normal subjects and PD patients with parkin mutations. We demonstrate that loss of parkin in human midbrain DA neurons greatly increases the transcription of monoamine oxidases and oxidative stress, significantly reduces DA uptake and increases spontaneous DA release. Lentiviral expression of parkin, but not its PD-linked mutant, rescues these phenotypes. The results suggest that parkin controls dopamine utilization in human midbrain DA neurons by enhancing the precision of DA neurotransmission and suppressing dopamine oxidation. Thus, the study provides novel targets and a physiologically relevant screening platform for disease-modifying therapies of PD. PMID- 22314365 TI - Psychological functioning and disease-related quality of life in pediatric patients with an implantable cardioverter defibrillator. AB - The objective of this multicenter study was to evaluate psychological functioning and disease-related quality of life (DRQoL) in pediatric patients with an implantable cardioverter defibrillator (ICD) in The Netherlands. Thirty patients were investigated; the mean age was 16.3 years, and the mean duration of implantation was 3.6 years. To assess psychological problems, three domains of the Symptom Checklist (SCL-90-R) were administered to the 25 patients[13 years old. DRQoL was assessed with a disease-specific pediatric questionnaire, the short-form 11-item Worries About (WA)ICDs Scale. Patients C13 years old scored significantly higher than the reference group on the domains of anxiety, depression, and sleeping problems of the SCL-90-R (T = 7.5, p?0.001; T = 5.4, p?0.001; and T = 7.8, p?0.001, respectively). Patients who had received an (in)appropriate shock reported more depressive symptoms (T = 2.1, p?0.03). Patients with [2 years implant duration (N = 19) or who had received an (in)appropriate shock (N = 13) showed lower DRQoL scores on the modified WAICD (T = 2.1, p?0.04; T = 2.1, p?0.5, respectively). Age at implantation or underlying disease did not influence psychological problems or DRQoL. Young ICD patients showed more anxiety, depression, and sleeping disorders. Worries were increased among patients with ICD shocks and in those who had their ICD implanted for[2 years. To determine psychological problems and help children to learn to cope with shocks, proper guidance and monitoring of young ICD patients are recommended. PMID- 22314366 TI - Vascular rings: presentation, imaging strategies, treatment, and outcome. AB - This study aimed to evaluate the presenting symptoms, the effectiveness of imaging methods, and the surgical treatment of vascular rings. Data for 44 patients (32 enrolled prospectively, 12 reviewed retrospectively) over a 10-year period in a tertiary referral center were analyzed. These patients comprised 25 patients with a left aortic arch and an aberrant right subclavian artery, 13 patients with a right aortic arch and a left subclavian artery originating from Kommerell's diverticulum, 1 patient with a right aortic arch and an aberrant left subclavian artery, 3 patients with a double aortic arch, and 2 patients with a pulmonary sling. Respiratory symptoms were found in 25 patients and dysphagia in 6 patients. Atypical symptoms such as reflex apnea, cyanosis, syncope episodes, and exercise-induced wheezing were noted in five patients. Associated congenital heart defects were detected in 41% of the patients. The diagnostic yield was 95.23% for barium esophagography, 54.54% for echocardiography, and 66.66% for computed tomography. The anatomy could be correctly identified by magnetic resonance imaging (MRI) in 97.43% and by angiography in 90.5% of the patients. Of the 30 patients who underwent surgery, 80% were completely relieved of symptoms during a mean follow-up period of 25 +/- 33.5 months. Vascular rings should not be overlooked in infants with atypical symptoms. The authors' diagnostic procedure of choice is MRI because it is superior to angiography for delineating the relationship between abnormal vascular structures, trachea, and esophagus. PMID- 22314367 TI - Perioperative management of infants undergoing fundoplication and gastrostomy after stage I palliation of hypoplastic left heart syndrome. AB - Infants with hypoplastic left heart syndrome (HLHS) represent a high-risk population when they present for noncardiac surgery. To assist clinicians in the care of these infants, we present our experience of 36 HLHS patients who underwent abdominal surgery after stage I palliation. We reviewed patients with HLHS who underwent gastrostomy and/or fundoplication after stage I palliation during an 18-month period. We assessed the impact of preoperative echocardiographic predictors and regional anesthesia on use of intraoperative inotropes, extubation in the OR, perioperative instability, postoperative escalation of care, and length of hospital and intensive care unit stay. Of 39 abdominal operations, all but 2 were performed with open laparotomy. There was a positive association between regional anesthesia and instability during induction. Escalation of respiratory care occurred in 9 (23.1%) cases, and escalation of hemodynamic care occurred in 6 (15.4%) cases. Neoaortic valve insufficiency was associated with increased length of stay, and ventricular outflow obstruction was associated with escalation of hemodynamic care. Extubation in the OR was successful in 31 cases (79.5%). In-hospital death occurred in 1 patient (2.7%). HLHS infants often undergo abdominal surgery, but intraoperative instability and need for escalation of care is common. Specific echocardiographic findings were associated with length of stay and escalation of care. Regional anesthesia was associated with transient intraoperative instability but not with other adverse outcomes. PMID- 22314368 TI - Sex and age differences in body-image, self-esteem, and body mass index in adolescents and adults after single-ventricle palliation. AB - Single-ventricle congenital heart disease (SVCHD) requires multiple palliative surgical procedures that leave visible surgical scars and physical deficits, which can alter body-image and self-esteem. This study aimed to compare sex and age differences in body-image, self-esteem, and body mass index (BMI) in adolescents and adults with SVCHD after surgical palliation with those of a healthy control group. Using a comparative, cross-sectional design, 54 adolescent and adult (26 male and 28 female) patients, age 15-50 years, with SVCHD were compared with 66 age-matched healthy controls. Body-image and self-esteem were measured using the Multidimensional Body-Self Relations Questionnaire-Appearance Scale and Rosenberg Self-Esteem Scale. Height and weight were collected from retrospective chart review, and BMI was calculated. Female adolescents and adult patients with SVCHD reported lower body image compared with males patients with SVCHD and healthy controls (p = 0.003). Specific areas of concern were face (p = 0.002), upper torso or chest (p = 0.002), and muscle tone (p = 0.001). Patients with SVCHD who were ?21 years of age had lower body image compared with healthy controls (p = 0.006). Self-esteem was comparable for both patients with SVCHD and healthy peers. There were no sex differences in BMI; BMI was higher in subjects[21 years of age (p = 0.01). Despite the similarities observed in self esteem between the two groups, female patients with SVCHD?21 years of age reported lower perceived body-image. Our findings support the need to recognize poor psychological adjustment related to low self-esteem in patients with SVCHD; female patients warrant increased scrutiny. Strategies to help patients with SVCHD cope with nonmodifiable aspects of body-image during the difficult adolescent-to-young adult years may potentially enhance self-esteem and decrease psychological distress. PMID- 22314369 TI - Relation between red cell distribution width and clinical outcome after surgery for congenital heart disease in children. AB - Recent studies have reported a strong association between increased red cell distribution width (RDW) and the risk of adverse outcomes for adults with heart failure. This study investigated the association between preoperative RDW and postoperative clinical outcomes for children with cardiac disease. The relation between preoperative RDW and the length of postoperative stay was tested with 688 consecutive children undergoing surgery for congenital heart disease (CHD). The RDW was significantly higher in patients who died during the postoperative hospital stay (mean, 18.34 +/- 4.69 vs 16.12 +/- 2.84; p = 0.004). The risk of postoperative death was five times higher for patients with an RDW of 16% or more. In the general study population, RDW correlated with the intensive care unit (ICU) stay (p < 0.0001) and with the total hospital stay in the local population (p < 0.0001). The correlation between RDW and ICU stay was stronger for patients with acyanotic CHD (p < 0.0001) than for those with cyanotic CHD (p = 0.0007), and for the subpopulation of patients with acyanotic CHD and normal hemoglobin level (p < 0.0001) than for anemic patients with acyanotic CHD (p = 0.025). Preoperative RDW is a strong predictor of an adverse outcome in children undergoing surgery for CHD, especially in nonanemic patients, for whom it reflects an underlying inflammatory stress. PMID- 22314370 TI - Use of a novel hybrid approach to salvage an attempted transcatheter pulmonary valve implant. AB - Transcatheter pulmonary valve implantation in the setting of right ventricle-to pulmonary artery conduit dysfunction is a relatively new procedure with encouraging early and midterm results. Malpositioning of the valve during implantation is a potentially serious complication. This report describes a case in which valve malpositioning was avoided by the use of a unique hybrid approach. This approach may prove to be useful for a select group of patients requiring pulmonary valve replacement. PMID- 22314371 TI - Urethane suppresses hippocampal CA1 neuron excitability via changes in presynaptic glutamate release and in potassium channel activity. AB - Urethane is a widely used anesthetic for animal experiments. Although urethane is thought to minimally interfere with neurophysiological processes and appears to preserve synaptic signal transmission, it has also been reported to produce depressive effects on neuronal excitability. In the present study, we used electrophysiological recordings to investigate the effects of urethane on rat hippocampal CA1 neurons. Whole-cell recordings were employed in a brain slice preparation to record discharges in current-clamp mode and sEPSCs or mEPSCs in voltage-clamp mode. Urethane was found to significantly increase both the interspike interval and the coefficient of variation of the firing. Moreover, it was found that the inter-event intervals of sEPSC/mEPSCs were increased, but the amplitude and the kinetic properties (rise time and decay time) of the sEPSC/mEPSC were not altered by urethane, which implies that potassium leak currents were involved in such effects. The results suggest that urethane significantly suppresses activity of hippocampal CA1 neurons and alters spontaneous pre-synaptic glutamatergic release possibly by activating potassium leak currents. PMID- 22314373 TI - Thickness-dependent morphological behavior of dendritic (PS)2-b-PLA copolymer thin films on a SiO2 substrate. AB - In contrast to the known perpendicular ordering of conventional PS-b-PLA thin films, branched (PS)(2)-b-PLA thin films showed two different parallel orientations whose locations are strongly dependent upon film thickness. PMID- 22314372 TI - AMPK isoform expression in the normal and failing hearts. AB - AMP-activated protein kinase (AMPK) is a master metabolic switch that plays an important role in energy homeostasis at the cellular and whole body level, hence a promising drug target. AMPK is a heterotrimeric complex composed of catalytic alpha-subunit and regulatory beta- and gamma-subunits with multiple isoforms for each subunit. It has been shown that AMPK activity is increased in cardiac hypertrophy and failure but it is unknown whether changes in subunit composition of AMPK contribute to the altered AMPK activity. In this study, we determined the protein expression pattern of AMPK subunit isoforms during cardiac development as well as during cardiac hypertrophy and heart failure in mouse heart. We also compared the findings in failing mouse heart to that of the human failing hearts in order to determine whether the mouse heart is a good model of AMPK in human diseases. In mouse developmental hearts, AMPK was highly expressed in the fetal stages and fell back to the adult level after birth. In the failing mouse heart, there was a significant increase in alpha2, beta2, and gamma2 subunits both at the mRNA and protein levels. In contrary, we found significant increases in the protein level of alpha1, beta1 and gamma2c subunits in human failing hearts with no change in the mRNA level. We also compared isoform-specific AMPK activity in the mouse and human failing hearts. Consistent with the literature, in the failing mouse heart, the alpha2 complexes accounted for ~2/3 of total AMPK activity while the alpha1 complexes accounted for the remaining 30-35%. In the human hearts, however, the contribution of alpha1-AMPK activity was significantly higher (>40%) in the non-failing hearts, and it further increased to 50% in the failing hearts. Thus, the human hearts have a greater amount of alpha1-AMPK activity compared to the rodent hearts. In summary, the protein level and the isoform distribution of AMPK in the heart change significantly during normal development as well as in heart failure. These observations provide a basis for future development of therapeutic strategies for targeting AMPK. PMID- 22314375 TI - Improvement in the assessment of direct and facilitated ion transfers by electrochemically induced redox transformations of common molecular probes. AB - A new strategy based on a thick organic film modified electrode allowed us, for the first time, to explore the voltammetric processes for a series of hydrophilic ions by electrochemically induced redox transformations of common molecular probes. During the limited time available for voltammetry, this thick organic film ensured that the generated product of the molecular probe, which is within a limited diffusion layer, was kept far away from the aqueous-organic solvent interface; therefore, regardless of the degree of hydrophobicity, the generated product never participates in ion exchange across the interface and the charge neutrality of the organic film (containing an extremely hydrophobic electrolyte) can only be maintained by the injection of ions from the aqueous phase. Taking advantage of this fact, common redox probes, such as ferrocene (Fc) and 7,7,8,8 tetracyanoquinodimethane (TCNQ), which are almost useless for both three-phase electrode (TPE) and thin-layer cyclic voltammetry (TLCV) methods, can induce the transfer of numerous highly hydrophilic anions and cations. Consequently, the majority of their Gibbs transfer energies have been accurately determined for the first time to the best of our knowledge. With this in mind, using TCNQ as a redox probe to induce facilitated cation transfer, a stategy that is more advantageous than traditional methods has been developed. The main advantages are that: (i) voltammetric experiments performed on this system were free from the polarized potential window (ppw) in the aqueous phase and, as a result, this allowed the assessment of weakly assisted ion transfers, which appear at the terminal of the ppw at single polarized interfaces; (ii) without introducing the tetraphenylarsonium-tetraphenylborate (TPAs-TPB) thermodynamic assumption, one can conveniently evaluate both the association constant and the stoichiometric parameter between the ion and its ionophore by comparison of their direct and facilitated ion transfer voltammograms. These encouraging results illustrated the exciting innovation for assessing direct and facilitated ion transfers based on this new thick organic film modified electrode. PMID- 22314376 TI - Contribution of Fibroblast and Mast Cell (Afferent) and Tumor (Efferent) IL-6 Effects within the Tumor Microenvironment. AB - Hyperactive inflammatory responses following cancer initiation have led to cancer being described as a 'wound that never heals'. These inflammatory responses elicit signals via NFkappaB leading to IL-6 production, and IL-6 in turn has been shown to induce epithelial to mesenchymal transition in breast cancer cells in vitro, implicating a role for this cytokine in cancer cell invasion. We previously have shown that conditioned medium derived from cancer-associated fibroblasts induced an Epithelial to Mesenchymal transition (EMT) in PMC42-LA breast cancer cells and we have now identify IL-6 as present in this medium. We further show that IL-6 is expressed approximately 100 fold higher in a cancer associated fibroblast line compared to normal fibroblasts. Comparison of mouse specific (stroma) and human-specific (tumor) IL-6 mRNA expression from MCF-7, MDA MB 468 and MDA MB 231 xenografts also indicated the stroma rather than tumor as a significantly higher source of IL-6 expression. Mast cells (MCs) feature in inflammatory cancer-associated stroma, and activated MCs secrete IL-6. We observed a higher MC index (average number of mast cells per xenograft section/average tumor size) in MDA MB 468 compared to MDA MB 231 xenografts, where all MC were observed to be active (degranulating). This higher MC index correlated with greater mouse-specific IL-6 expression in the MDA MB 468 xenografts, implicating MC as an important source of stromal IL-6. Furthermore, immunohistochemistry on these xenografts for pSTAT3, which lies downstream of the IL-6 receptor indicated frequent correlations between pSTAT3 and mast cell positive cells. Analysis of publically available databases for IL-6 expression in patient tissue revealed higher IL-6 in laser capture microdissected stroma compared to adjacent tissue epithelium from patients with inflammatory breast cancer (IBC) and invasive non-inflammatory breast cancer (non-IBC) and we show that IL-6 expression was significantly higher in Basal versus Luminal molecular/phenotypic groupings of breast cancer cell lines. Finally, we discuss how afferent and efferent IL-6 pathways may participate in a positive feedback cycle to dictate tumor progression. PMID- 22314377 TI - Developing fluorescent hyaluronan analogs for hyaluronan studies. AB - Two kinds of fluorescent hyaluronan (HA) analogs, one serving as normal imaging agent and the other used as a biosensitive contrast agent, were developed for the investigation of HA uptake and degradation. Our approach of developing HA imaging agents depends on labeling HA with varying molar percentages of a near-infrared (NIR) dye. At low labeling ratios, the hyaluronan uptake can be directly imaged while at high labeling ratios, the fluorescent signal is quenched and signal generation occurs only after degradation. It is found that the conjugate containing 1%-2% NIR dye can be used as a normal optical imaging agent, while bioactivable imaging agents are formed at 6% to 17% dye loading. It was determined that the conjugation of dye to HA with different loading percentages does not impact HA biodegradation by hyaluronidase (Hyal). The feasibility of using these two NIR fluorescent hyaluronan analogs for HA investigation was evaluated in vivo with optical imaging. The data demonstrates that the 1% dye loaded fluorescent HA can be used to monitor the behavior of HA and its fragments, whereas bioactivatable HA imaging agent (17% dye in HA) is more suitable for detecting HA fragments. PMID- 22314378 TI - Carotenoids of lettuce (Lactuca sativa L.) grown on soil enriched with spent coffee grounds. AB - The impact of spent coffee grounds on carotenoid and chlorophyll content in lettuce (Lactuca sativa L. var. capitata) was evaluated. A greenhouse pot experiment was conducted with spent coffee amounts ranging from 0% to 20% (v/v). All evaluated pigments increased proportionally to spent coffee amounts. Lutein and beta-carotene levels increased up to 90% and 72%, respectively, while chlorophylls increased up to 61%. Biomass was also improved in the presence of 2.5% to 10% spent coffee, decreasing for higher amounts. Nevertheless, all plants were characterized by lower organic nitrogen content than the control ones, inversely to the spent coffee amounts, pointing to possible induced stress. Collected data suggests that plants nutritional features, with regards to these bioactive compounds, can be improved by the presence of low amounts of spent coffee grounds (up to 10%). This observation is particularly important because soil amendment with spent coffee grounds is becoming increasingly common within domestic agriculture. Still, further studies on the detailed influence of spent coffee bioactive compounds are mandatory, particularly regarding caffeine. PMID- 22314379 TI - Benzoxetes and benzothietes--heterocyclic analogues of benzocyclobutene. AB - Benzo-condensed four-ring heterocycles, such as benzoxetes 1 and benzothietes 3 represent multi-purpose starting compounds for the preparation of various higher heterocyclic ring systems. The thermal or photochemical valence isomerizations between the benzenoid forms 1,3 and the higher reactive o-quinoid structures 2,4 provide the basis for the synthetic applications. On the other hand, this valence isomerization impedes in particular the generation and storage of 1 because the thermal equilibrium 1<=> 2 is completely on the side of 2. Thus, the number of erroneous or questionable benzoxete structures published to date is surprisingly high. On the contrary, the thermal equilibrium 3<=> 4 is on the side of the benzothietes 3, which makes them easily accessible, especially by different flash vacuum pyrolysis techniques. The present article gives a survey of the preparations of 1 and 2, and tries to stimulate their use in synthetic projects. Naphtho-condensed and higher condensed compounds and compounds with an exocyclic C=O or S=O double bond (lactones, thiolactones, sulfoxides and sulfones) are not covered in this article. PMID- 22314380 TI - Anthocyanins and their variation in red wines I. Monomeric anthocyanins and their color expression. AB - Originating in the grapes, monomeric anthocyanins in young red wines contribute the majority of color and the supposed beneficial health effects related to their consumption, and as such they are recognized as one of the most important groups of phenolic metabolites in red wines. In recent years, our increasing knowledge of the chemical complexity of the monomeric anthocyanins, their stability, together with the phenomena such as self-association and copigmentation that can stabilize and enhance their color has helped to explain their color representation in red wine making and aging. A series of new enological practices were developed to improve the anthocyanin extraction, as well as their color expression and maintenance. This paper summarizes the most recent advances in the studies of the monomeric anthocyanins in red wines, emphasizing their origin, occurrence, color enhancing effects, their degradation and the effect of various enological practices on them. PMID- 22314381 TI - Phloxine B as a probe for entrapment in microcrystalline cellulose. AB - The photophysical behaviour of phloxine B adsorbed onto microcrystalline cellulose was evaluated by reflectance spectroscopy and laser induced time resolved luminescence in the picosecond-nanosecond and microsecond-millisecond ranges. Analysis of the absorption spectral changes with concentration points to a small tendency of the dye to aggregate in the range of concentrations under study. Prompt fluorescence, phosphorescence and delayed fluorescence spectral decays were measured at room temperature and 77 K, without the need of sample degassing because cellulose protects triplet states from oxygen quenching. In all cases, spectral changes with time and lifetime distribution analysis were consistent with the dye coexisting in two different environments: dyes tightly entrapped between polymer chains in crystalline regions of cellulose showed longer fluorescence and phosphorescence lifetimes and more energetic triplet states, while dyes adsorbed in more amorphous regions of the support showed shorter lifetimes and less energetic triplet states. This behaviour is discussed in terms of the different dye-support interactions in both kinds of adsorption sites. PMID- 22314382 TI - Enantioselective synthesis of 2,2-disubstituted terminal epoxides via catalytic asymmetric Corey-Chaykovsky epoxidation of ketones. AB - Catalytic asymmetric Corey-Chaykovsky epoxidation of various ketones with dimethyloxosulfonium methylide using a heterobimetallic La-Li(3)-BINOL complex (LLB) is described. The reaction proceeded smoothly at room temperature in the presence of achiral phosphine oxide additives, and 2,2-disubstituted terminal epoxides were obtained in high enantioselectivity (97%-91% ee) and yield ( > 99% 88%) from a broad range of methyl ketones with 1-5 mol% catalyst loading. Enantioselectivity was strongly dependent on the steric hindrance, and other ketones, such as ethyl ketones and propyl ketones resulted in slightly lower enantioselectivity (88%-67% ee). PMID- 22314383 TI - Prebiotic activity of polysaccharides extracted from Gigantochloa levis (Buluh beting) shoots. AB - Bamboo shoot crude polysaccharides (BSCP) extracted from the shoots of Gigantochloa levis gave about 3.27 +/- 0.18% on dry basis and a very minute percentage of protein (0.02 +/- 0.01%). The molecular weight of BSCP estimated by gel chromatography was found to be around 7.49 * 103 Da, while the molecular weights of purified fractions (F1 to F5) were around 1550.96, 1471.63, 1685.78, 1691.61 and 1551.67 Da, respectively. The FTIR spectrum of BSCP revealed the possibility that the extract contains beta-glucan, which can be considered a valuable compound for the medical and food industries. These relate to the resistance of BSCP towards artificial human gastric juice which is more than 99%. Prebiotic activity tested using BSCP as a carbon source showed significant increase in the growth of B. animalis ATCC 1053, B. longum BB 536 and L. acidophilus ATCC 4356 as compared to the use of FOS. Survivality of S. choleraesuis JCM 6977 was found to be slower in both BSCP and FOS. Study conducted reflects a good sign for the BSCP to be exploited as a promising prebiotic. PMID- 22314384 TI - Palynological origin, phenolic content, and antioxidant properties of honeybee collected pollen from Bahia, Brazil. AB - The aim of this study was to determine the palynological origin, phenolic and flavonoid content, and antioxidant properties of twenty-five samples of bee pollen harvested during a nine-month period (February-November) from the Canavieiras municipality (northeastern Brazil). Of the 25 samples analyzed, only two (February 01 and 02) were heterofloral. The predominant pollens in the samples analyzed during that month were: Cecropia, Eucalyptus, Elaeis, Mimosa pudica, Eupatorium, and Scoparia. Ethyl acetate fractions were analyzed by HPLC DAD. The flavonoids isoquercetin, myricetin, tricetin, quercetin, luteolin, selagin, kaempferol, and isorhamnetin were detected. The flavonoid present in all 22 samples was isolated and identified as isorhamnetin 3-O-b-neohesperidoside. The total phenolic contents determined using the Folin-Ciocalteu reagent ranged from 41.5 to 213.2 mg GAE/g. Antioxidant activities based on the 1,1-diphenyl-2 picryl hydrazyl (DPPH), 2,2-azinobis 3-ethylbenzothiozoline-6-sulfonic acid (ABTS), and Fe2+ ion chelating activity assays were observed for all extracts, and correlated with the total phenolic content. PMID- 22314386 TI - Cadmium-induced effects on cellular signaling pathways in the liver of transgenic estrogen reporter mice. AB - Estrogen-like effects of cadmium (Cd) have been reported in several animal studies, and recent epidemiological findings suggest increased risk of hormone dependent cancers after Cd exposure. The mechanisms underlying these effects are still under investigation. Our aim was to study the effects of Cd on cellular signaling pathways in vivo with special focus on estrogen signaling and to perform benchmark dose analysis on the effects. Transgenic adult ERE-luciferase male mice were exposed subcutaneously to 0.5-500 MUg CdCl(2) per kg body weight (bw) or 17alpha-ethinylestradiol (EE2) for 3 days. These doses had no effects on organ and bw or testicular histology, indicating subtoxic exposure levels. The transgene luciferase, reporting genomic estrogen response, was significantly increased by EE2 but not by Cd. However, Cd significantly affected kinase phosphorylation and endogenous gene expression. Interestingly, gene expression changes displayed a traditional dose-response relationship, with benchmark dose levels for the expression of Mt1, Mt2, p53, c-fos, and Mdm2 being 92.9, 19.9, 7.6, 259, and 25.9 MUg/kg bw, respectively, but changes in kinase phosphorylation were only detected at low exposure levels. Phosphorylation of Erk1/2 was significantly increased even in the lowest dose group, 0.5 MUg/kg bw, rendering pErk1/2 a more sensitive sensor of exposure than changes in gene expression. Collectively, our data suggest that the effects triggered by Cd in vivo are markedly concentration dependent. Furthermore, we conclude that the estrogen-like effects of Cd are likely to result from a mechanism different from steroidal estrogens. PMID- 22314385 TI - The novel antibacterial compound walrycin A induces human PXR transcriptional activity. AB - The human pregnane X receptor (PXR) is a ligand-regulated transcription factor belonging to the nuclear receptor superfamily. PXR is activated by a large, structurally diverse, set of endogenous and xenobiotic compounds and coordinates the expression of genes central to metabolism and excretion of potentially harmful chemicals and therapeutic drugs in humans. Walrycin A is a novel antibacterial compound targeting the WalK/WalR two-component signal transduction system of Gram (+) bacteria. Here, we report that, in hepatoma cells, walrycin A potently activates a gene set known to be regulated by the xenobiotic sensor PXR. Walrycin A was as efficient as the reference PXR agonist rifampicin to activate PXR in a transactivation assay at noncytotoxic concentrations. Using a limited proteolysis assay, we show that walrycin A induces conformational changes at a concentration which correlates with walrycin A ability to enhance the expression of prototypic target genes, suggesting that walrycin A interacts with PXR. The activation of the canonical human PXR target gene CYP3A4 by walrycin A is dose and PXR dependent. Finally, in silico docking experiments suggest that the walrycin A oxidation product Russig's blue is the actual ligand for PXR. Taken together, these results identify walrycin A as a novel human PXR activator. PMID- 22314387 TI - Deferoxamine reverses radiation induced hypovascularity during bone regeneration and repair in the murine mandible. AB - BACKGROUND: Deferoxamine (DFO) is an iron-chelating agent that has also been shown to increase angiogenesis. We hypothesize that the angiogenic properties of DFO will improve bone regeneration in distraction osteogenesis (DO) after x-ray radiation therapy (XRT) by restoring the vascularity around the distraction site. MATERIAL AND METHODS: Three groups of Sprague-Dawley rats underwent distraction of the left mandible. Two groups received pre-operative fractionated XRT, and one of these groups was treated with DFO during distraction. After consolidation, the animals were perfused and imaged with micro-CT to calculate vascular radiomorphometrics. RESULTS: Radiation inflicted a severe diminution in the vascular metrics of the distracted regenerate and consequently led to poor clinical outcome. The DFO treated group revealed improved DO bone regeneration with a substantial restoration and proliferation of vascularity. CONCLUSIONS: This set of experiments quantitatively demonstrates the ability of DFO to temper the anti-angiogenic effect of XRT in mandibular DO. These exciting results suggest that DFO may be a viable treatment option aimed at mitigating the damaging effects of XRT on new bone formation. PMID- 22314388 TI - Specificity of Pseudomonas isolates on healthy and Fusarium head blight-infected spikelets of wheat heads. AB - The specificity of culturable bacteria on healthy and Fusarium head blight (FHB) infected spikelets of wheat heads was investigated to find a candidate of biocontrol agents against FHB. The bacterial genus Pseudomonas was commonly isolated from the tissues, and phylogenetic analysis using 16S ribosomal RNA gene sequences of isolates of the genera revealed that particular phylogenetic groups in the genus specifically inhabited either healthy or infected spikelet tissues. The specificity of each group was suggested to be due to differences in the ability to form biofilms and colonize spikelet tissues; isolates originated from healthy spikelets formed biofilms on polyvinyl chloride microplate wells and highly colonized the spikelet tissues. Other bacterial groups obtained from FHB infected spikelets less formed biofilms and attached with low densities on the spikelet tissues. Their colonization on the tissues, however, was promoted when co-inoculated with the causal pathogenic fungus, Fusarium graminearum, and several isolates were observed to smash the mycelia in vivo. Moreover, based on results of in vitro mycelial growth inhibition activity, the diseased tissue originated isolates were verified to have a negative effect on the fungal growth. These results suggest that Pseudomonas isolates obtained from infected spikelet tissues were highly associated with the FHB pathogen and have potential as candidates for biological control against FHB. PMID- 22314389 TI - Metastatic pheochromocytoma and paraganglioma: focus on therapeutics. AB - Metastatic pheochromocytomas and paragangliomas are rare and challenging tumors. The tumor burden, combined with excessive catecholamine production, predispose to a broad spectrum of complications that range from spinal cord compression to any organ damage, all of which may lead to decreased quality of life and overall survival. Current therapies include surgery, systemic chemotherapy and radiopharmaceutical agents. Surgery is often a preferred therapy because it may cure or allow a long-term remission in patients with locoregional or isolated resectable distant metastases. Additionally, surgery can palliate symptoms related to tumor burden or catecholamine excess. However, in patients for whom surgery is not an option, systemic chemotherapy and radiopharmaceutical agents are preferred options. Systemic chemotherapy and radiopharmaceutical agents such as 131I-Metaiodobenzylguanidine (131I-MIBG) may cause partial responses or stabilization of disease with better blood pressure control and symptomatic and performance status improvement. However, as these therapies are only palliative, patients' quality of life and personal preferences should always be considered. The recognition of molecular pathways involved in the pheochromocytoma and paraganglioma tumorigenesis has driven the development of new therapeutic options. Agents such as tyrosine kinase, MAPK, PI3K, or hypoxia inducible factor inhibitors, alone or in combination, may represent novel therapeutic strategies that could be evaluated in prospective clinical trials. Transcriptional profiling and the development of personalized cancer medicine will help to pave the way for more specific therapeutic approaches and combinations. PMID- 22314390 TI - Toxicity and genotoxicity of organic and inorganic nanoparticles to the bacteria Vibrio fischeri and Salmonella typhimurium. AB - The present work aimed at evaluating the toxicity and genotoxicity of two organic (vesicles composed of sodium dodecyl sulphate/didodecyl dimethylammonium bromide SDS/DDAB and of monoolein and sodium oelate-Mo/NaO) and four inorganic (titanium oxide-TiO2, silicon titanium-TiSiO4, Lumidot-CdSe/ZnS, and gold nanorods) nanoparticles (NP), suspended in two aqueous media (Milli Q water and American Society for Testing and Materials (ASTM) hardwater), to the bacteria Vibrio fischeri (Microtox test) and Salmonella typhimurium-his- (Ames test with strains TA98 and TA100). Aiming a better understanding of these biological responses physical and chemical characterization of the studied NP suspensions was carried out. Results denoted a high aggregation state of the NP in the aqueous suspensions, with the exception of SDS/DDAB and Mo/NaO vesicles, and of nanogold suspended in Milli Q water. This higher aggregation was consistent with the low values of zeta potential, revealing the instability of the suspensions. Regarding toxicity data, except for nano TiO2, the tested NP significantly inhibited bioluminescence of V. fischeri. Genotoxic effects were only induced by SDS/DDAB and TiO2 for the strain TA98. A wide range of toxicity responses was observed for the six tested NP, differing by more than 5 orders of magnitude, and suggesting different modes of action of the tested NP. PMID- 22314391 TI - Spectrum of gastroparesis in children. AB - BACKGROUND: Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical outlet obstruction. Symptoms may include nausea, vomiting, bloating, early satiety, abdominal pain, and weight loss. Delayed gastric emptying of a solid-phase meal assessed by radionuclear scintigraphy is the criterion standard for diagnosis. The prevalence of GP is difficult to estimate due to the lack of a validated, widely available diagnostic test that can be applied in primary care. The extent of this problem in children is unknown. METHODS: We studied a cohort of children with GP diagnosed by radionuclear scintigraphy to identify demographics, symptoms, comorbidities, treatment, and outcomes. A retrospective analysis of 239 patients between ages 0 and 21 years was performed. RESULTS: The mean age of presentation was 7.9 years, and boys and girls were almost equally affected, that is, 48.5% and 51.5%, respectively. Vomiting was the most frequent presenting symptom (68%), followed by abdominal pain (51%), nausea (28%), weight loss (27%), early satiety (25%), and bloating (7%). Almost 75% of patients responded to intravenous erythromycin administered provocatively during gastric scintigraphy. In a majority of the patients, no cause was identified, that is, idiopathic GP (70%), followed by drugs (18%) and postsurgical (12.5%) causes. Only 4% patients had diabetic GP, and our population was essentially narcotic naive (2%). After an average of 24 months' follow-up, the most common complication was esophageal reflux (67%). Despite different therapeutic modalities, by the end of the follow-up period, a significant improvement in symptoms was reported by an average of 60%, regardless of sex, age, or degree of emptying delay. CONCLUSIONS: GP has a good prognosis in childhood despite different etiologies, symptom presentation, and therapy. PMID- 22314392 TI - Accuracy of pain recall in children. AB - BACKGROUND AND AIM: Chronic abdominal pain (AP) is common in children. Recall of symptoms is used clinically to determine management, to assess treatment progress, and in drug studies to assess outcomes. Limited data exist on accuracy of AP recall in children. The aim of the present study was to assess ability to accurately recall AP in children. METHODS: The study was a secondary analysis of data obtained from a double-blind, randomized, placebo-controlled trial, evaluating amitriptyline in children with functional gastrointestinal disorders. Children ages 8 to 17 years with AP predominant functional gastrointestinal disorders based on Rome II criteria were recruited from 6 centers. Those with evidence of organic disease were excluded. Patients maintained AP diary daily for 1 month (presence, frequency, and intensity). At the end of the study, patients reported the number of days of AP during previous month. Agreement between daily pain reports and recalled pain was assessed. Univariate analysis was conducted with Spearman rank correlations. RESULTS: We recruited 63 children (45 girls, mean age 12.8 years). Sixteen percent children had perfect agreement on number of days of AP. Fifty-four percent of children recalled fewer episodes of pain. The average number of days with AP by recall was 17.7/month, whereas by diary it was 23.5/month (P = 0.001). Correlation between patient recall of the last week of symptoms (r = 0.47) was no better than correlation between recall of the last 30 days of symptoms (r = 0.48). On comparing AP recall versus various pain intensities, reported AP did not reflect only AP of greater severity. Higher correlation of recall of symptoms was seen in children 11 years or younger (r = 0.59) as compared with children older than 11 years (r = 0.26). CONCLUSIONS: Few children can accurately recall the episodes of AP. Children commonly recall a lower frequency of AP than that assessed by prospective diary reports. Reported recall does not reflect a shorter recollection period. Recall is not related to intensity of pain. Adolescents have worse recall of symptoms. PMID- 22314393 TI - Investigation of short-term variations in casein and whey proteins in breast milk of term mothers. AB - OBJECTIVES: We investigated changes in breast milk whey and casein proteins, between fore and hind milk during breast expression, between breasts and within 24-hour period during breast-feeding. This has implications for developing an appropriate sampling protocol for investigating the influence of milk composition on gastric emptying and infants' feeding behaviour. METHODS: Breast milk samples were collected from mothers (n = 25) of healthy term infants ages 1 to 8 months. A total of 17 mothers provided fore and hind milk samples, which were collected during simultaneous expression of both breasts. Fifteen mothers provided samples from each breast-feed during 24-hour period, of which samples were selected from 4 time points (morning, day, evening, night). Whey and casein were isolated from skim milk, and protein concentration of the skim, whey, and casein fractions were determined. RESULTS: Mean protein concentrations were found to be 13.5 +/- 2.1 (skim milk), 7.6 +/- 1.5 (whey), and 3.4 +/- 0.97 g/L (casein). Protein concentrations were not significantly different between fore and hind milk. During a 24-hour period, no significant differences were found in protein concentration of any fraction at the 4 time points or between left and right breasts. Large variations were seen between mothers with coefficient of variances of 15.5%, 19.8%, and 28.4% for skim milk, whey, and casein, respectively. CONCLUSIONS: Although there was wide variation between mothers, the small variations within mothers indicate that for sampling purposes, a single breast milk sample (fore or hind from each breast at any time point of the day) will be representative of that mother's protein concentration of skim, whey, and casein fractions for that day. PMID- 22314394 TI - Parental knowledge of fecal incontinence in children. AB - OBJECTIVES: Fecal incontinence (FI) is a common and stressful symptom of constipation in children. Recurrent FI causes psychological and physiological changes, complicating treatment as symptom duration progresses; however, parental misconceptions about the causes of FI may delay seeking medical care. The aim of the present study was to assess parental knowledge about FI and determine how this relates to the care and treatment of FI. METHODS: A questionnaire was developed from qualitative interviews and clinician input. The questionnaire was administered to 251 parents and tested for reliability and validity. Subscales were compared between parents who did and did not consult a clinician. In addition, 30 parents completed the questionnaire before and after consultation with a pediatric gastroenterologist and after 2 months of treatment. RESULTS: Two subscales were identified with good psychometric properties: "Blame and Punish" and "Worry and Help." Families who consulted a physician for their child's FI acknowledged the role of constipation and scored higher on Worry and Help (mean 36.4 vs mean 46.9; P < 0.0001). Trends were found for Blame and Punish to decrease after consultation with a pediatric gastroenterologist (mean 1.7 vs 1.5; P = 0.08) and after 2 months of treatment (mean 1.5; P = 0.08). CONCLUSIONS: Parental knowledge about FI changes with physician consultation. These findings can help in developing educational materials for parents to encourage early diagnosis and treatment and prevent chronic problems that are difficult to manage. PMID- 22314395 TI - Severe ischemic pancreatitis following the use of extracorporeal membrane oxygenation. PMID- 22314396 TI - Pediatric obesity and gallstone disease. AB - OBJECTIVES: The aim of the present study was to investigate the association between childhood and adolescent obesity, the risk of gallstones, and the potential effect modification by oral contraceptive use in girls. METHODS: For this population-based cross-sectional study, measured weight and height, oral contraceptive use, and diagnosis of cholelithiasis or choledocholithiasis were extracted from the electronic medical records of 510,816 patients ages 10 to 19 years enrolled in an integrated health plan, 2007-2009. RESULTS: We identified 766 patients with gallstones. The adjusted odds ratios (95% CI) of gallstones for under-/normal-weight (reference), overweight, moderate obesity, and extreme obesity in boys were 1.00, 1.46 (0.94%-2.27%), 1.83 (1.17%-2.85%), and 3.10 (1.99%-4.83%) and in girls were 1.00, 2.73 (2.18%-3.42%), 5.75 (4.62%-7.17%), and 7.71 (6.13%-9.71%), respectively (P for interaction sex * weight class <0.001). Among girls, oral contraceptive use was associated with higher odds for gallstones (odds ratio 2.00, 95% CI 1.66%-2.40%). Girls who used oral contraceptives were at higher odds for gallstones than their counterparts in the same weight class who did not use oral contraceptives (P for interaction weight class * oral contraceptive use 0.023). CONCLUSIONS: Due to the shift toward extreme childhood obesity, especially in minority children, pediatricians can expect to face increasing numbers of children and adolescents affected by gallstone disease. PMID- 22314398 TI - Primary clavicle tumors and tumorous lesions: a review of 206 cases in East Asia. AB - PURPOSE: The aim of this study is to systematically review the published literature from East Asia on the clinical, pathological, and epidemiological characteristics of primary clavicle tumor and tumorous lesions. METHODS: A computerized search based on keywords "clavicle," "tumor," and "tumorous lesion" (both in Chinese and in English) was performed on literature published from 1980 to 2011 in East Asian countries, including China, Japan, South Korea, North Korea, and Mongolia. An analysis was carried out with unified inclusion and exclusion criteria. RESULTS: Two hundred and six cases were identified. The age of onset ranged from 1.5 to 70, with an average age of 29.4, and a male/female ratio of 1.53:1. Lesion locations included 28.9% in medial third, 18.8% in the middle third, and 33.6% in the lateral third of the clavicle. Another 7.4% involved both the medial and middle thirds, 7.4% involved both the middle and lateral thirds, and 4.0% involved the entire length of the clavicle. Major pathological types included 18.5% eosinophilic granuloma, 10.2% plasmocytoma, 7.8% Ewing sarcoma, 8.7% osteosarcoma, 8.7% osteochondroma, and 5.3% chondrosarcoma. The age of onset was found to be strongly correlated with the benign/ malignant ratio. Clavicle malignancy was rarely found in patients younger than 10 years, while the incidence of malignancy greatly increased among patients over 40 years old. Total or subtotal claviculectomy was the most common treatment in cases for which treatment information was available. Of these, 40.8% of patients received reconstruction with allograft or autograft. CONCLUSIONS: Clavicle tumors and tumorous lesions in East Asia had an inclined occurrence in respect to age and gender. The most common tumors were eosinophilic granuloma and tumors derived from the bone marrow hematopoietic system. Age of onset was found to be a risk factor for malignancy. These characteristics may be related to the special tissue structures and mode of development in the clavicle as well as to the genetic traits of the typical Mongoloids in East Asia. PMID- 22314397 TI - Inhibition of high-mobility group box 1 protein (HMGB1) enhances bacterial clearance and protects against Pseudomonas Aeruginosa pneumonia in cystic fibrosis. AB - Pulmonary infection with Pseudomonas aeruginosa and neutrophilic lung inflammation significantly contribute to morbidity and mortality in cystic fibrosis (CF). High-mobility group box 1 protein (HMGB1), a ubiquitous DNA binding protein that promotes inflammatory tissue injury, is significantly elevated in CF sputum. However, its mechanistic and potential therapeutic implications in CF were previously unknown. We found that HMGB1 levels were significantly elevated in bronchoalveolar lavage fluids (BALs) of CF patients and cystic fibrosis transmembrane conductance regulator (CFTR )(-/-) mice. Neutralizing anti-HMGB1 monoclonal antibody (mAb) conferred significant protection against P. aeruginosa-induced neutrophil recruitment, lung injury and bacterial infection in both CFTR(-/-) and wild-type mice. Alveolar macrophages isolated from mice treated with anti-HMGB1 mAb had improved phagocytic activity, which was suppressed by direct exposure to HMGB1. In addition, BAL from CF patients significantly impaired macrophage phagocytotic function, and this impairment was attenuated by HMGB1-neutralizing antibodies. The HMGB1-mediated suppression of bacterial phagocytosis was attenuated in macrophages lacking toll like receptor (TLR)-4, suggesting a critical role for TLR4 in signaling HMGB1 mediated macrophage dysfunction. These studies demonstrate that the elevated levels of HMGB1 in CF airways are critical for neutrophil recruitment and persistent presence of P. aeruginosa in the lung. Thus, HMGB1 may provide a therapeutic target for reducing bacterial infection and lung inflammation in CF. PMID- 22314399 TI - Percutaneous vertebroplasty for pathological vertebral compression fractures secondary to multiple myeloma. AB - BACKGROUND: Vertebral compression fractures are common in multiple myeloma. Percutaneous vertebroplasty is used to stabilize vertebral collapse and treat the pain. The major technical drawbacks of percutaneous vertebroplasty are the potential for neural comprise and pulmonary embolism of cement from leakage of polymethylmethacrylate into epidural space and perivertebral veins. We have retrospectively evaluated the safety and complication of percutaneous vertebroplasty in the vertebral compression fractures resulting from multiple myeloma. METHODS: From August 2003 to July 2008, we describe 24 patients with multiple myeloma who were treated for vertebral compression fractures with percutaneous vertebroplasty to a total of 36 vertebrae. There were 4 male and 20 female patients with an average age of 67 (range 54-81 years). The pain symptoms were measured on a visual analog pain scale and quality of life as measured by the physical component summary scale of the Short Form- 36 before operation and at 24 h, at 3 months and at 1 year following vertebroplasty. Radiography was reviewed for evidence of cement leakage and pulmonary complication. RESULTS: The mean visual analog pain scale decreased from a preoperative value of 9.0-3.8 at 24 h following operation and SF-36 score improved from 22.1 to 41.8. Of the twenty-four patients, four had cement leakage (2 leak through inferior endplate into disc, 2 leak into perivertebral vessels). There were no intra-postoperative neurologic or pulmonary complications. Eight patients died 2-18 months post operatively due to multiple myeloma-related organ failure. CONCLUSIONS: In this study, vertebroplasty significantly improved pain scores and function and, thereby, the quality of life. There were no major procedure-related complications in this study. Direct cytotoxic effect, polymerization and biomechanical microfractures stabilizer of polymethylmethacrylate play multiple roles in pain relief. In multiple myeloma, when pathological spinal compression fractures cause intractable pain and are unresponsive to conservative treatment, vertebroplasty remains the best option for pain relief and is effective in increasing quality of life. PMID- 22314401 TI - Cell death: Programmed necrosis: putting the pieces together. PMID- 22314400 TI - Septins: the fourth component of the cytoskeleton. AB - Septins belong to a family of proteins that is highly conserved in eukaryotes and is increasingly recognized as a novel component of the cytoskeleton. All septins are GTP-binding proteins that form hetero-oligomeric complexes and higher-order structures, including filaments and rings. Recent studies have provided structural information about the different levels of septin organization; however, the crucial structural determinants and factors responsible for septin assembly remain unclear. Investigations on the molecular functions of septins have highlighted their roles as scaffolds for protein recruitment and as diffusion barriers for subcellular compartmentalization in numerous biological processes, including cell division and host-microorganism interactions. PMID- 22314402 TI - Defining sarcopenia: the impact of different diagnostic criteria on the prevalence of sarcopenia in a large middle aged cohort. AB - Sarcopenia, low muscle mass, is an increasing problem in our ageing society. The prevalence of sarcopenia varies extremely between elderly cohorts ranging from 7% to over 50%. Without consensus on the definition of sarcopenia, a variety of diagnostic criteria are being used. We assessed the degree of agreement between seven different diagnostic criteria for sarcopenia based on muscle mass and handgrip strength, described in literature. In this cross-sectional study, we included men (n=0325) and women (n=0329) with complete measurements of handgrip strength and body composition values as measured by bioimpedance analysis within the Leiden Longevity Study. Prevalence of sarcopenia was stratified by gender and age. In men (mean age 64.5 years), the prevalence of sarcopenia with the different diagnostic criteria ranged from 0% to 20.8% in the lowest age category (below 60 years), from 0%to 31.2% in the middle (60 to 69 years) and from 0% to 45.2% in the highest age category (above 70 years). In women (mean age 61.8 years), the prevalence of sarcopenia ranged from 0% to 15.6%, 0% to 21.8% and 0% to 25.8% in the lowest, middle and highest age category, respectively. Only one participant (0.2%) was identified having sarcopenia according to all diagnostic criteria that marked prevalence above 0%. We conclude that the prevalence of sarcopenia is highly dependent on the applied diagnostic criteria. It is necessary to reach a consensus on the definition of sarcopenia in order to make studies comparable and for implementation in clinical care. PMID- 22314403 TI - Association of handgrip strength with chronic diseases and multimorbidity: a cross-sectional study. AB - The prevalence of chronic diseases has risen along with increased longevity. Co occurrence of two or more chronic diseases in an individual (multimorbidity) is prevalent and poses a huge burden to individuals and the society. However, determinants of multimorbidity are largely unknown. Handgrip strength is a general indicator of muscle strength and linked with premature mortality. However, its role in multimorbidity has never been evaluated. To investigate the relationships between handgrip strength and multiple chronic diseases and multimorbidity, and to assess the usefulness of age and handgrip as a marker of chronic diseases and multimorbidity in a community dwelling sample of men and women, we analyzed a cross-sectional cohort with 1,145 subjects (748 men and 397 women) aged 50 years and older living in Hong Kong. Low handgrip strength was significantly associated with increased odds of having five and three chronic diseases in men and women, respectively, after controlling for age, body mass index, history of smoking, educational level, marital level and comorbidity. Multivariable-adjusted handgrip strength was significantly decreased with the number of chronic diseases in men (trend, P = 0.001), but the trend in women was marginal (trend, P = 0.06). Conversely, multivariable-adjusted age was significantly increased with the number of chronic diseases in women (trend, P = 0.033), but not in men (trend, P = 0.118). In conclusion, handgrip strength is associated with multiple chronic diseases and multimorbidity in men and women after adjustment of confounding factors. It shows a linear trend of association with the number of chronic diseases in men, but not in women. Since handgrip strength is a biomarker of multiple physiological systems, its augmentation may be a feasible strategy to improve general health and decrease likelihood of having multiple chronic diseases and hence, premature mortality. PMID- 22314404 TI - A copper thiolate centre for electron transfer: mononuclear vs. dinuclear complexes. AB - We have structurally and spectroscopically investigated a rare example of a mononuclear aliphatic dithiolate Cu(II) complex characterized by a reversible Cu(II)/Cu(I) redox couple. By DFT, we have shown that this system has a lower reorganization energy than its previously described bis(MU-thiolato) dicopper parent complex, which reversibly cycles between the Cu(1.5)Cu(1.5) and Cu(I)Cu(I) redox states. PMID- 22314405 TI - Current world literature. PMID- 22314407 TI - Positive feedback in the Akt/mTOR pathway and its implications for growth signal progression in skeletal muscle cells: an analytical study. AB - The IGF-1 mediated Akt/mTOR pathway has been recently proposed as mediator of skeletal muscle growth and a positive feedback between Akt and mTOR was suggested to induce homogeneous growth signals along the whole spatial extension of such long cells. Here we develop two biologically justified approximations which we study under the presence of four different initial conditions that describe different paradigms of IGF-1 receptor-induced Akt/mTOR activation. In first scenario the activation of the feedback cascade was assumed to be mild or protein turnover considered to be high. In turn, in the second scenario the transcriptional regulation was assumed to maintain defined levels of inactive pro enzymes. For both scenarios, we were able to obtain closed-form formulas for growth signal progression in time and space and found that a localised initial signal maintains its Gaussian shape, but gets delocalised and exponentially degraded. Importantly, mathematical treatment of the reaction diffusion system revealed that diffusion filtered out high frequencies of spatially periodic initiator signals suggesting that the muscle cell is robust against fluctuations in spatial receptor expression or activation. However, neither scenario was consistent with the presence of stably travelling signal waves. Our study highlights the role of feedback loops in spatiotemporal signal progression and results can be applied to studies in cell proliferation, cell differentiation and cell death in other spatially extended cells. PMID- 22314408 TI - Discovery and structural insight of a highly selective protein kinase inhibitor hit through click chemistry. AB - Novel bisaryl maleimide derivatives to mimic natural kinase inhibitors were prepared through click chemistry. A highly selective hit was discovered in a 124 kinase-assay, and docking studies revealed a pi-pi stacking interaction with the Phe67 at the P-loop of GSK-3beta kinase. PMID- 22314409 TI - The efficacy and safety of antiviral therapy with lamivudine to stop the vertical transmission of hepatitis B virus. AB - The purpose of this study was to investigate the efficacy and safety of lamivudine (LAM) in stopping the vertical transmission of hepatitis B virus (HBV). Pregnant women with normal alanine transaminase (ALT) (n = 100) and with abnormal ALT (n = 100) who were positive for hepatitis B e antigen (HBeAg), and with HBV DNA (deoxyribonucleic acid) levels >=1.0 * 107 copies/ml were enrolled in this study. One hundred volunteers (50 with normal ALT, 50 with abnormal ALT) received 100 mg of LAM daily from the 24th to 32nd week of gestation and the untreated 100 volunteers served as controls. All infants received passive-active immunoprophylaxis. Compared to the control group, the study group got a marked reduction in serum levels (P < 0.001) and high negativity (P < 0.001) of HBV DNA before delivery. They also got normalization in ALT levels as much as controls received general medication (P > 0.05). The prenatal transmission rate in the study group was significantly lower than that of the control group (P < 0.05). There were no differences in incidences of congenital malformation between the two groups (P > 0.05). LAM treatment can effectively and safely stop vertical transmission of HBV and normalize the ALT levels of pregnant women. PMID- 22314410 TI - Prevention of group B streptococcal neonatal disease revisited. The DEVANI European project. AB - The purpose of this paper was to present the current knowledge on the prevention of group B streptococcus (GBS) neonatal infections and the status of prevention policies in European countries and to present the DEVANI pan-European program, launched in 2008. The aim of this program was to assess the GBS neonatal infection burden in Europe, to design a new vaccine to immunize neonates against GBS infections, to improve the laboratory performance for the diagnosis of GBS colonization and infection, and to improve the methods for the typing of GBS strains. The current guidelines for GBS prevention in different countries were ascertained and a picture of the burden before and after the instauration of prevention policies has been drawn. After the issue of the Centers for Disease Control and Prevention (CDC) guidelines, many European countries have adopted universal screening for the GBS colonization of pregnant women and intrapartum prophylaxis to colonized mothers. Nevertheless, some European countries continue advocating the risk factor approach to GBS prevention. Most European countries have implemented policies to prevent GBS neonatal infections and the burden of the disease has decreased during the last several years. Nevertheless, further steps are necessary in order to develop new strategies of prevention, to improve microbiological techniques to detect GBS colonization and infection, and to coordinate the prevention policies in the EU. PMID- 22314411 TI - Clostridium difficile O27 colitis: hospital-onset but community-acquired. AB - Large outbreaks of Clostridium difficile (CD) associated colitis in North America and Europe have been attributed to the emergence of the epidemic/toxin PCR Ribotype O27 CD strain (CD027). Due to the increased virulence of this epidemic strain and its propension for causing outbreaks, we performed a structured risk assessment approach in order to determine the risks associated with the introduction of this strain within our university hospital. From February 2009 to January 2010, we identified 31 cases of CD027 associated colitis, whereby twenty one (67.7%) had symptoms onset more than 48 hours after admission and were classified as nosocomial. These patients had received wide-spectrum antimicrobials for other infections in the hospital before CD027 colitis diagnosis. The 31 patients with CD027 were admitted in 20 different units, managed by distinct health-care workers (HCWs), and no contact was identified between patients during their hospital stay. Furthermore, infection control audits showed 100% compliance with institutional guidelines for control of CD colitis. These findings suggest that CD027 is most frequently acquired in the community and emerges sporadically under antibiotic pressure during hospitalization. PMID- 22314412 TI - High and selective CO2 capture by two mesoporous acylamide-functionalized rht type metal-organic frameworks. AB - Two mesoporous and flexible acylamide-functionalized rht-type MOFs exhibit not only high excess unsaturation CO(2) uptake (157 wt%) at 20 bar and 273 K, but also good selectivity of CO(2)/CH(4) (8.6) and CO(2)/N(2) (34.3). The advantages of acylamide groups for CO(2) capture have been further confirmed by GCMC and first-principles calculations. PMID- 22314413 TI - Electronic and magnetic properties of the two-dimensional C4H-type polymer with strain effects, intrinsic defects and foreign atom substitutions. AB - Following the two-dimensional periodic single-layer sheet successful synthesized experimentally very recently [Adv. Mater., 2011, 23, 4497], we present systematically the electronic and magnetic properties of this novel polymer (referred to as C(4)H) without and with strain-modifying, vacancy-doping, and nonmetal element (B, N, and P) doping by means of first-principles calculations. It was found that: (a) the C(4)H sheet is a nonmagnetic semiconductor with a wide indirect band gap. (b) The atomic structure, binding energies and electronic properties of the C(4)H sheet could be significantly modified by applying strain. (c) Vacancy defects can lead to intrinsic magnetism in C(4)H and, surprisingly, the induced spin polarization has large spatial extension; especially, room temperature ferromagnetism in H vacancies-doped case is quite feasible. (d) Substitution of B, P and N at the unhydrogenated C site could form a local magnetic moment, whereas no spin-polarization could be induced for that with N at the hydrogenated C site. The present study provides theoretical insight leading to a better understanding of novel 2D structures, and further experimental studies are expected to confirm the attractive predictions. PMID- 22314414 TI - Cytotoxic triterpenoid saponins from Ardisia gigantifolia. AB - Three new triterpenoid saponins, 1- 3, together with two known saponins, 4 and 5, were isolated from the rhizome of Ardisia gigantifolia. Their structures were elucidated by 1D and 2D NMR spectroscopic studies. Saponins 1, 2, 4, and 5 exhibited significant cytotoxicity against four human cancer cell lines, namely, Hela human cervical carcinoma cells, EJ human bladder tumor cells, HepG-2 human hepatoma cells, and BCG human gastric carcinoma cells with IC (50) values in the range of 1.9-4.8 uM. PMID- 22314415 TI - Metabolic discrimination of rhizoma coptidis from different species using 1H NMR spectroscopy and principal component analysis. AB - Rhizoma coptidis, a broadly used medicinal plant, originates from the dried rhizomes of three species in Chinese pharmacopoeia, namely, Coptis chinensis Franch, Coptis deltoidea C. Y. Cheng et Hsiao, and Coptis teeta Wall. In this study, a novel approach using (1)H NMR spectroscopy combined with multivariate analysis was introduced to differentiate the three species and identify potential metabolic markers for better controlling the quality of rhizoma coptidis. A broad range of metabolites including alkaloids, sugars, organic acids, amino acids, and fatty acids present in rhizoma coptidis were detected by means of (1)H NMR spectroscopy. Principal component analysis (PCA) of the (1)H NMR data set showed a clear separation between all samples by PC1 and PC3, and some metabolites that could be responsible for the discrimination of the three species were identified. An analysis of variance (ANOVA) was performed to statistically verify the significance of differences in metabolite levels between species. By combining PCA and ANOVA, significantly higher contents of palmatine, coptisine, epiberberine, columbamine, and fatty acids together with lower contents of jateorrhizine were found in Coptis chinensis, whereas Coptis deltoidea and Coptis teetA showed the highest levels of sucrose and chlorogenic acid, respectively. This study indicates that metabolites of rhizoma coptidis vary with the species and the proposed method is suitable for metabolic fingerprinting analysis to check the genuine origin of rhizoma coptidis. PMID- 22314416 TI - The RIPK2 gene: a positional candidate for tick burden supported by genetic associations in cattle and immunological response of knockout mouse. AB - Ticks and tick-borne diseases have a detrimental impact on livestock production causing estimated losses of around $200 million per year in Australia alone. Host resistance to ticks is heritable, within-breed heritability estimates being around 0.35, and with large differences between breeds. Previously a QTL for tick burden was detected on BTA14 at ~72 Mb distal to the centromere, near the gene receptor-interacting serine-threonine kinase 2 (RIPK2). To identify polymorphisms in this region, we sequenced all exons of the RIPK2 gene, identifying 46 single nucleotide polymorphism (SNP). Using SNP from RIPK2 as well as SNP from the bovine genome sequence, we genotyped two samples, one of 1,122 taurine dairy cattle and one of 761 zebu and zebu composite beef cattle. We confirmed that SNP and haplotypes from this region, including from RIPK2, were associated with tick burden in both dairy and beef cattle. To determine whether RIPK2 influences response to tick salivary gland extract (SGE), an immunisation experiment with tick SGE in a RIPK2 knockout (RIPK2 -/-) mouse strain was conducted. There was a significant (P < 0.05) reduction in IgG production in the RIPK2 -/- mouse in response to the SGE compared to its background strain C57BL/ 6 as well as the outbred CD1 mouse strain. In addition, antibodies generated by RIPK2 -/- mice recognised a different set of antigens within SGE when compared to parental derived antibodies. In summary, the SNP association with tick burden at BTA14 was confirmed and quantitative and qualitative differences in antibody production were observed between RIPK2 -/- and wild-type mice. PMID- 22314418 TI - Network-based discovery of gene signature for vascular invasion prediction in HCC. PMID- 22314417 TI - Gestational age at birth and risk of testicular cancer. AB - Most testicular germ cell tumors originate from carcinoma in situ cells in fetal life, possibly related to sex hormone imbalances in early pregnancy. Previous studies of association between gestational age at birth and testicular cancer have yielded discrepant results and have not examined extreme preterm birth. Our objective was to determine whether low gestational age at birth is independently associated with testicular cancer in later life. We conducted a national cohort study of 354,860 men born in Sweden in 1973-1979, including 19,214 born preterm (gestational age < 37 weeks) of whom 1,279 were born extremely preterm (22-29 weeks), followed for testicular cancer incidence through 2008. A total of 767 testicular cancers (296 seminomas and 471 nonseminomatous germ cell tumors) were identified in 11.2 million person-years of follow-up. Extreme preterm birth was associated with an increased risk of testicular cancer (hazard ratio = 3.95; 95% confidence interval = 1.67-9.34) after adjusting for other perinatal factors, family history of testicular cancer and cryptorchidism. Only five cases (three seminomas and two nonseminomas) occurred among men born extremely preterm, limiting the precision of risk estimates. No association was found between later preterm birth, post-term birth or low or high fetal growth and testicular cancer. These findings suggest that extreme but not later preterm birth may be independently associated with testicular cancer in later life. They are based on a small number of cases and will need confirmation in other large cohorts. Elucidation of the key prenatal etiologic factors may potentially lead to preventive interventions in early life. PMID- 22314419 TI - Non-invasive diagnosis of non-alcoholic steatohepatitis by combined serum biomarkers. AB - BACKGROUND & AIMS: The diagnosis of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) is limited by the need for liver biopsy. We aimed at testing the accuracy of cytokeratin-18 fragment (CK-18), adipocyte fatty acid binding protein (AFABP) and fibroblast growth factor 21 (FGF21) for the diagnosis of NAFLD and NASH. METHODS: 146 patients with biopsy-proven NAFLD and 74 age- and gender-matched healthy controls were included. Serum CK-18, AFABP and FGF21 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Serum CK 18, AFABP, and FGF21 increased in a stepwise fashion in control subjects (median 103 U/L, 15.4 ng/ml, and 104 pg/ml), patients with non-NASH NAFLD (263 U/L, 18.9 ng/ml, and 249 pg/ml) and NASH (418 U/L, 19.4 ng/ml, and 354 pg/ml) (p<0.001, 0.060, and 0.016, respectively). The area under receiver-operating characteristics curve to diagnose NAFLD and NASH was 0.91 and 0.70 for CK-18, 0.66 and 0.59 for AFABP, and 0.84 and 0.62 for FGF21. At cut-offs of 203 and 670 U/L, CK-18 had 71% negative predictive value (NPV) and 77% positive predictive value (PPV) to exclude and diagnose NASH. A 2-step approach measuring CK-18 followed by FGF21 further improved the NPV to 74% and PPV to 82%. In a validation cohort of 51 patients with paired liver biopsies, the NPV and PPV of the 2-step approach were 67% and 78%, respectively. CONCLUSIONS: CK-18 is the most accurate biomarker for NAFLD and NASH. A two-step approach using CK-18 and FGF21 further improves the accuracy in diagnosing NASH. PMID- 22314420 TI - Non-invasive diagnosis of hepatocellular carcinoma <= 2 cm in cirrhosis. Diagnostic accuracy assessing fat, capsule and signal intensity at dynamic MRI. AB - BACKGROUND & AIMS: To prospectively assess the diagnostic accuracy of the incorporation of additional magnetic resonance imaging (MRI) parameters in those based on contrast enhancement pattern for the diagnosis of solitary nodules between 5 and 20mm, detected during surveillance in patients with cirrhosis. METHODS: Between November 2003 and January 2010, we prospectively included 159 cirrhotic patients with a newly detected solitary nodule between 5 and 20mm in diameter by screening ultrasonography (US). Hepatic MRI and fine-needle biopsy were performed in all patients. RESULTS: Final diagnoses were hepatocellular carcinoma (HCC) (n=103), other malignant lesions (intrahepatic cholangiocarcinoma/metastases) (n=4), and benign lesions (n=52). The specific enhancement pattern (arterial enhancement followed by washout) yielded a sensitivity and specificity of 58.3% and 96.4%, respectively. Peritumoral capsule was present in 43 HCC and in 2 non-HCC lesions. Intralesional fat was detected in 24 nodules; 5 nodules were non-HCC. Finally, the presence of both capsule and fat was observed in 10 cases, all of them HCC (100% specificity), but all of them also displayed the specific enhancement pattern, thus adding no sensitivity or specificity. CONCLUSIONS: Conclusive non-invasive diagnosis of HCC in cirrhosis should be based only on the contrast enhancement pattern, while other characteristics at MRI do not increase the diagnostic accuracy. PMID- 22314421 TI - Phase II study of concurrent transarterial chemoembolization and sorafenib in patients with unresectable hepatocellular carcinoma. AB - BACKGROUND & AIMS: Transarterial chemoembolization (TACE) is an important palliative treatment for unresectable hepatocellular carcinoma (HCC), but TACE induced ischemic injury can upregulate angiogenic factors and is associated with poor prognosis. The aim of this study was to evaluate the safety and efficacy of concurrent conventional TACE and sorafenib in patients with unresectable HCC. METHODS: The primary objectives of this prospective, single-arm, phase II study were to evaluate safety and time to progression (TTP). Sorafenib was given 3 days after TACE and was administered for up to 24 weeks. Repeated TACE was performed on demand. Tumor response was assessed every 8 weeks. RESULTS: Fifty patients were treated and followed from July 2009 to May 2011. All patients were in Barcelona Clinic Liver Cancer (BCLC) stage B (82%) or C (18%). The median time of follow-up was 14.9 months and a median of 1 TACE session was given (range, 1-4). The median dose intensity of sorafenib was 68.7% (range, 37.3-100) of 800 mg daily. The most common reasons for dose reduction were hand-foot syndrome and thrombocytopenia. Thirty patients completed the study and 17 patients discontinued sorafenib due to disease progression. The overall median TTP was 7.1 months (95% confidence interval (CI), 4.8-7.5 months): 7.3 months in BCLC stage B; 5.0 months in BCLC stage C. The 6-month progression-free survival rate was 52% (95% CI, 37.3-66.1). CONCLUSIONS: Concurrent treatment of unresectable HCC with conventional TACE and sorafenib demonstrates a manageable safety profile and a possibility of promising efficacy. PMID- 22314422 TI - Decreased infectivity of nucleoside analogs-resistant hepatitis B virus mutants. AB - BACKGROUND & AIMS: To understand the mechanisms of emergence and selection of HBV polymerase variants, which may also harbor mutations in the overlapping envelope protein, we analyzed the in vitro virus production and infectivity of the main viral mutants resistant to lamivudine and adefovir. METHODS: HBV-resistant mutants (rtL180M+M204V, rtV173L+L180M+M204V, rtM204I, rtL180M+M204I, rtN236T, rtA181V, rtA181V+rtN236T, rtA181T+N236T, and rtA181T) were produced in HepG2 cells permanently expressing the respective viral genomes. Viral protein expression, secretion, and viral particle production were studied by ELISA, Western blot, and transmission electron microscopy. To study only the effect of surface gene mutants on virus infectivity, HepaRG cells were inoculated with HDV pseudo-particles coated with the mutant HBV envelopes. To evaluate infectivity and replication in a global fashion, HepaRG cells were inoculated with HBV mutants. RESULTS: HBeAg was expressed and secreted in cell supernatants in all mutant-expressing cell lines. As expected, mutants harboring a sW196Stop mutation in the surface gene did not express small envelope proteins. All mutants expressing HBsAg were able to produce viral particles. HDV particles coated with mutant envelopes were less infectious than WT in HepaRG cells. Finally, we found that resistant mutants exhibit lower infectivity and replication ability than WT virus. CONCLUSIONS: Based on this study, we found that envelope substitutions modulate viral protein expression, HDV coating, and viral infectivity. These envelope modifications provide novel insights into the features of emerging HBV variants during antiviral therapies and suggest that such mutants are less prone to transmission than their WT counterpart. PMID- 22314423 TI - Refined prediction of week 12 response and SVR based on week 4 response in HCV genotype 1 patients treated with peginterferon alfa-2a (40KD) and ribavirin. AB - BACKGROUND & AIMS: It is unclear whether the magnitude of reduction in hepatitis C virus (HCV) RNA between baseline and week 4 of treatment influences the probability of achieving a sustained virological response (SVR) in patients without a week 4 rapid virological response (RVR). METHODS: Data were retrospectively analyzed from two studies in which treatment-naive patients received peginterferon alfa-2a (40KD) 180 MUg/week plus ribavirin 1000/1200 mg/day for 48 weeks. Five hundred and fifty-eight genotype 1 patients with evaluable HCV RNA at baseline and week 4 were grouped according to RVR status: RVR (HCV RNA<50 IU/ml) or no RVR. Non-RVR patients were subdivided into discrete mutually exclusive categories according to week 4 HCV RNA; the proportion of patients with undetectable HCV RNA at week 12 was calculated per each category, and among them, the proportion with an SVR. RESULTS: Overall, 88% of RVR patients and 43% of non-RVR patients achieved an SVR (p<0.0001). Among non-RVR patients, SVR rates were 77%, 61%, 43%, 27% and 13%, respectively (trend test p<0.0001) in those with unquantifiable HCV RNA or >= 3 log(10), >= 2 log(10), >= 1 log(10), or<1 log(10) drop to week 4. In patients HCV RNA positive at week 4, SVR rates were 67% for those negative at week 12 vs. 17% (HCV RNA positive patients or who had missing values at week 12 [p<0.0001]). CONCLUSIONS: The probability of achieving SVR is graded in relation to the magnitude of reduction in HCV RNA at week 4 and 12. Patients with a >= 3 log(10) drop in HCV RNA at week 4 have a high probability of achieving an SVR. PMID- 22314424 TI - Diagnostic and therapeutic potential of miRNA signatures in patients with hepatocellular carcinoma. AB - MicroRNAs (miRNAs) are evolutionary conserved small non-coding RNAs that regulate gene expression by mediating post-transcriptional silencing of target genes. Since miRNAs are involved in fine-tuning of physiological responses, they have become of interest for diagnosis and therapy of a number of diseases. Moreover, the role of dysregulated miRNAs in maintaining the malignant phenotype has profound implications for cancer therapy. We will review the best defined cellular miRNAs and changes in their expression profile in hepatocellular carcinoma (HCC). Cellular miRNAs can also be released into the circulation, and these miRNAs are detected in most body fluids. Circulating miRNAs are associated with HCC and are possible biomarkers. Finally, by affecting several clinically relevant targets, artificially increasing or decreasing the expression level of a given miRNA offers fascinating therapeutic perspectives. We will therefore highlight recent developments in miRNA-based gene therapy with a focus on their therapeutic potential for HCC. PMID- 22314425 TI - A phase 1, randomized, placebo-controlled, 3-day, dose-ranging study of GS-5885, an NS5A inhibitor, in patients with genotype 1 hepatitis C. AB - BACKGROUND & AIMS: GS-5885 is an inhibitor of the hepatitis C virus (HCV) NS5A protein and exhibits potent suppression of genotype 1 HCV replicons. The safety, tolerability, pharmacokinetics, antiviral activity, and resistance profile of once-daily GS-5885 doses of 1-90 mg were evaluated in patients with chronic genotype 1 HCV. METHODS: Genotype 1 HCV-infected patients were randomized to 3 days of once-daily (QD) dosing with placebo (n=12) or GS-5885 1 mg (n=10), 3 mg (n=10), 10 mg (n=20), 30 mg (n=10), or 90 mg (n=10). Plasma samples for pharmacokinetics, HCV RNA, and NS5A sequencing were collected through day 14. RESULTS: GS-5885 was well tolerated and resulted in median maximal reductions in HCV RNA ranging from 2.3 log(10) IU/ml (1 mg QD) to 3.3 log(10) IU/ml (10 mg QD in genotype 1b and 30 mg QD). E(max) modeling indicated GS-5885 30 mg was associated with>95% of maximal antiviral response to HCV genotype 1a. HCV RNA reductions were generally more sustained among patients with genotype 1b vs. 1a. Three of 60 patients had a reduced response and harbored NS5A-resistant virus at baseline. NS5A sequencing identified residues 30 and 31 in genotype 1a, and 93 in genotype 1b as the predominant sites of mutation following GS-5885 dosing. Plasma pharmacokinetics was consistent with QD dosing. CONCLUSIONS: During 3 days of monotherapy, low doses of GS-5885 demonstrated significant antiviral activity in genotype 1a and 1b HCV-infected patients. GS-5885 is currently being evaluated in combination with direct antiviral regimens with and without peginterferon. PMID- 22314426 TI - Macrophages: central regulators of hepatic fibrogenesis and fibrosis resolution. PMID- 22314427 TI - Futility and rationing in liver retransplantation: when and how can we say no? PMID- 22314428 TI - Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using Drug Eluting Beads. Implications for clinical practice and trial design. AB - BACKGROUND & AIMS: Transarterial chemoembolisation (TACE) improves survival of properly selected patients with hepatocellular carcinoma (HCC). Drug eluting beads (DEB) provide a calibrated and homogenous procedure while increasing efficacy. Outcome data applying this technology is lacking, and this is instrumental for clinical decision-making and for trial design. We evaluated the survival of HCC patients treated with DEB-TACE following a strict selection (preserved liver function, absence of symptoms, extrahepatic spread or vascular invasion). METHODS: We registered baseline characteristics, the development of treatment-related adverse events, and the overall survival of all HCC patients treated by DEB-TACE from February 2004 to June 2010. RESULTS: One hundred and four patients were treated with DEB-TACE. All but one were cirrhotic, 62.5% HCV+, 95% Child-Pugh A, 41 BCLC-A and 63 BCLC-B. Causes of DEB-TACE treatment in BCLC-A patients were: 35 unfeasible ablation, and six post-treatment recurrences. After a median follow-up of 24.5 months, 38 patients had died, two patients had received transplantation and 24 had received sorafenib because of untreatable tumour progression. Median survival of the cohort was 48.6 months (95% CI: 36.9 61.2), while it was 54.2 months in BCLC stage A and 47.7 months in stage B. Median survival after censoring follow-up at time of transplant/sorafenib was 47.7 (95%CI: 37.9-57.5) months. CONCLUSIONS: These data validate the safety of DEB-TACE and show that the survival expectancy applying current selection criteria and technique is better than that previously reported. A 50% survival at 4 years should be considered when suggesting treatment for patients fitting into controversial scenarios such as expanded criteria for transplantation/resection for multifocal HCC. PMID- 22314429 TI - Comparison of two non-contemporaneous HCV-liver transplant cohorts: strategies to improve the efficacy of antiviral therapy. AB - BACKGROUND & AIMS: In a previous study, advanced fibrosis was associated with worsening efficacy of antiviral therapy in HCV-transplant patients. We aimed at assessing whether changes in treatment policy, that is starting therapy at lesser stages of fibrosis, have resulted in improved efficacy. METHODS: Efficacy (rapid, early, end-of-treatment, and sustained viral response (SVR)) and tolerability (peginterferon (pIFN)/ribavirin (RBV) doses, premature discontinuation, dose reductions, anemia, growth factors, transfusions) were compared between two non contemporaneous cohorts of post-LT naive patients treated with pIFN-RBV: Group 1 (n=44), a historical cohort of patients treated during the period 2005-2007 and Group 2 (n=70), patients treated more recently (2007-2010), where treatment was started once there was evidence of fibrosis. RESULTS: SVR increased from 25% to 54% (p=0.002) due to a reduction in relapse rate. Comparing both cohorts, a decrease in the number of cirrhotic patients together with an increase in platelet count was observed in recent years. Additional non-intentional changes included: (i) an increase of patients treated under cyclosporine immunosuppression, (ii) treatment-related factors with an increase in patients treated with initial full pIFN and RBV doses, who developed anemia and hence required dose modifications and erythropoietin. Baseline factors associated with SVR were younger donor age, lack of cirrhosis or severe necroinflammation and the use of RBV at full doses at initiation while on-treatment variables were adherence and viral kinetics. CONCLUSIONS: Treatment in the absence of cirrhosis is associated with higher SVR warranting strict disease progression monitoring. A more aggressive approach, particularly regarding RBV dosage, is also associated with improved efficacy. Further studies are required to assess whether switching to cyclosporine will result in improved SVR. PMID- 22314430 TI - IL28B and PNPLA3 polymorphisms affect histological liver damage in patients with non-alcoholic fatty liver disease. AB - BACKGROUND & AIMS: Genetic background may affect liver damage in patients with non-alcoholic fatty liver disease (NAFLD). The main outcomes of the study were to assess whether IL28B rs12979860 and rs8099917 polymorphisms, together with PNPLA3 rs738409 C>G polymorphism, are associated with lobular inflammation and fibrosis, in NAFLD patients. METHODS: One hundred sixty consecutive NAFLD patients were assessed by liver biopsy (Kleiner score); anthropometric, and biochemical and metabolic features were included. IL28B rs12979860 C>T, IL28B rs8099917 G>C, and PNPLA3 rs738409 C>G single nucleotide polymorphisms were tested. RESULTS: Seventy four (46.2%) patients had IL28B rs12979860 CC polymorphism, compared with 72 (45%) and 14 (8.8%) with TC and TT variants, respectively. PNPLA3 rs738409 CC polymorphism was present in 47 (29.4%) patients, compared with 79 (49.4%) and 34 (21.3%) with CG and GG variants, respectively. Multivariate logistic regression analysis showed that age (OR 1.043, 95% CI 1.012-1.075, p=0.007), triglycerides (OR 1.005, 95% CI 1.000-1.010, p=0.04), hyperuricemia (OR 5.027, 95% CI 1.839 13.742, p=0.002), IL28B rs12979860 TT/TC (OR 0.219, 95% CI 0.101-0.472, p<0.001), and steatosis grade (OR 1.704, 95% CI 1.048-2.773, p=0.03) were independently linked to moderate-severe lobular inflammation. Finally, IL28B rs12979860 CC was associated with severe fibrosis (F3-F4) on univariate analysis, even if only older age (OR 1.064, 95% CI 1.026-1.104, p=0.001), high HOMA (OR 1.213, 95% CI 1.068-1.377, p=0.003), and lobular inflammation (OR 3.181, 95% CI 1.438-7.036, p=0.004), remained associated in multivariate logistic regression analysis. CONCLUSIONS: In NAFLD patients, IL28B rs12979860 CC genotype, together with PNPLA3 rs738409 GG, is associated with the severity of liver damage. PMID- 22314431 TI - C-reactive protein predicts short-term mortality in patients with cirrhosis. AB - BACKGROUND & AIMS: We aimed at improving prediction of short-term mortality in cirrhotic inpatients by evaluating C-reactive protein (CRP) as a surrogate marker of systemic inflammatory response syndrome (SIRS). METHODS: One-hundred and forty eight consecutive cirrhotic patients with Child-Pugh score >= B8 and without hepatocellular carcinoma were prospectively included and followed for 182 days. The primary end point was 6-month survival. RESULTS: Main baseline characteristics were as follows: alcoholic liver disease in 88.5%; bacterial infection in 37%; hepatorenal syndrome in 7% of cases. CRP range was 1-240 mg/L (median 26 mg/L); 42 patients (28.4%) had SIRS as defined by ACCP/SCCM-criteria. CRP levels were higher in patients with SIRS (50 vs. 21 mg/L; p<0.0001), infection (46 vs. 27 mg/L; p<0.0001), and alcoholic hepatitis (44 vs. 32 mg/L, p=0.049). Forty-two patients died within the first 6 months of follow-up. Short term mortality was associated with extrahepatic co-morbidities (p=0.002), high MELD score (p<0.001; AUROC=0.67), renal failure (p=0.008), elevated blood lactates (p<0.001), and high baseline CRP levels (p=0.003; AUROC=0.63; best cut off value at 29 mg/L). Among patients with baseline CRP >= 29 mg/L, 32 still had CRP >= 29 mg/L at day 15 (group A). Group A was associated with 6-month mortality in the overall population (p<0.001) and also through sensitivity analyses restricted to patients without infection or alcoholic hepatitis. Multivariate analysis (Cox) adjusted for age identified three predictors of mortality: high MELD score (HR=1.08; 95% CI: 1.03-1.12; p<0.001), extrahepatic co-morbidities (HR=2.51; 95% CI: 1.31-4.84; p=0.006), and CRP level (group A) (HR=2.73; 95% CI: 1.41-5.26; p=0.003). The performance of the three variables taken together for predicting death was 0.80 (AUROC). CONCLUSIONS: In Child-Pugh score >= B8 cirrhotic patients, persistent CRP levels >= 29 mg/L predicted short-term mortality independently of age, MELD, and co-morbidities, and better than infection or clinically-assessed SIRS. PMID- 22314432 TI - Management of anemia in advanced breast and lung cancer patients in daily practice: results of a French survey. AB - INTRODUCTION: The purpose of this French survey was to evaluate the adherence to the guidelines (European Organisation for Research and Treatment of Cancer [EORTC]; American Society of Clinical Oncology [ASCO]; French Standards, Options, and Recommendations [SOR]; European Society of Medical Oncology [ESMO]; Food and Drug Administration [FDA]; and National Comprehensive Cancer Network [NCCN]) for the use of erythropoiesis-stimulating agents (ESAs) in the management of chemotherapy- induced anemia for patients with advanced breast and lung cancers. METHODS: Two-hundred patients were recruited for each malignancy. The collected items were characteristics of ESA initiation, treatment, adjustment, and discontinuation. Metastatic breast cancer and stage IIIb/IV lung cancer patients who had received chemotherapy were eligible. The endpoint was to compare French daily practices with national and international guidelines. RESULTS: From November 2010 to December 2010, 185 breast cancer and 227 lung cancer files were collected. The main reason of ESA initiation was the correction of anemia (49% and 44%, respectively). The median baseline value of hemoglobin was 9.5 g/dL, and the median target value was 12 g/dL. The mean duration of treatment was 12 and 14 weeks, respectively. The mean gain of hemoglobin was 2.3 g/dL and 1.9 g/dL, respectively. In the breast cancer population, two patients (1%) developed a thromboembolic event, which is lower than what has been described in the literature. An iron supplement was prescribed in 55% of patients with breast cancer and 49% of those with lung cancer, with about one-third administered intravenous iron. The interruption of ESA and chemotherapy was synchronous in about 20% of cases, and was earlier in lung cancer patients than in breast cancer patients. CONCLUSION: The quality and the rigor of the sampling represent one of the key points of this survey. The French and international guidelines for the use of ESA were well respected by the physicians. Overall, the management of chemotherapy-induced anemia was improved compared with what was described in the historical surveys (European Cancer Anaemia Survey [ECAS], French Anaemia Cancer Treatment [F-ACT]). PMID- 22314433 TI - Multidisciplinary breast centres in Germany: a review and update of quality assurance through benchmarking and certification. AB - PURPOSE: This review summarizes the rationale for the creation of breast centres and discusses the studies conducted in Germany to obtain proof of principle for a voluntary, external benchmarking programme and proof of concept for third-party dual certification of breast centres and their mandatory quality management systems to the German Cancer Society (DKG) and German Society of Senology (DGS) Requirements of Breast Centres and ISO 9001 or similar. In addition, we report the most recent data on benchmarking and certification of breast centres in Germany. METHODS: Review and summary of pertinent publications. Literature searches to identify additional relevant studies. Updates from the DKG/DGS programmes. RESULTS AND CONCLUSIONS: Improvements in surrogate parameters as represented by structural and process quality indicators suggest that outcome quality is improving. The voluntary benchmarking programme has gained wide acceptance among DKG/DGS-certified breast centres. This is evidenced by early results from one of the largest studies in multidisciplinary cancer services research, initiated by the DKG and DGS to implement certified breast centres. The goal of establishing a nationwide network of certified breast centres in Germany can be considered largely achieved. Nonetheless the network still needs to be improved, and there is potential for optimization along the chain of care from mammography screening, interventional diagnosis and treatment through to follow up. Specialization, guideline-concordant procedures as well as certification and recertification of breast centres remain essential to achieve further improvements in quality of breast cancer care and to stabilize and enhance the nationwide provision of high-quality breast cancer care. PMID- 22314434 TI - Bee-honey and yogurt: a novel mixture for treating patients with vulvovaginal candidiasis during pregnancy. AB - OBJECTIVE: To evaluate the clinical and mycological cure rates of a novel mixture consisting of Bee-honey and yogurt compared to local antifungal agents for treating patients with vulvo-vaginal candidiasis (VVC) during pregnancy. MATERIALS AND METHODS: This is a prospective comparative study which included 129 patients with VVC during pregnancy. The participants were allocated into study group (n = 82) who received a mixture of Bee-honey and yogurt vaginally and control group (n = 47) who received local anti-fungal agents. The Chi-square test was used to evaluate the clinical and mycological cure rates and the side-effects of both modes of therapy. RESULTS: The clinical cure rate was significantly higher in the study than the control group (87.8 vs. 72.3%, respectively) while the mycological cure rate was higher in the control than the study group (91.5 vs. 76.9%, respectively). Both types of therapy were favorably tolerated by most of the patients. Side effects were reported only in 24.3 and 29.7% of patients in group I and II, respectively (p < 0.05). CONCLUSIONS: The mixture of Bee-honey and yogurt produced a high clinical cure rate and a reasonable mycological cure rate. It can be used as a complementary or an alternative to antifungal agents especially in patients with VVC during pregnancy. PMID- 22314435 TI - Association of the CC chemokine receptor 5 (CCR5) polymorphisms with preeclampsia in Turkish women. AB - AIM: Endothelial dysfunction and inflammation are involved in the pathogenesis of preeclampsia. The CC chemokine receptor 5 (CCR5) modulates inflammation secondary to endothelial dysfunction and related vascular disorders, by initiating chemotaxis. In this study, we examined the frequency of two polymorphisms, the CCR5D32 deletion and the CCR5-59029 A/G promoter point mutation in women with preeclampsia. METHODS: The CCR5 polymorphisms were genotyped in 74 preeclamptic and 128 controls who had been unaffected by preeclampsia in previous pregnancies. Genotyping was performed with the polymerase chain reaction and restriction fragment length polymorphism. Statistical evaluations were made using the chi square test or Fisher's exact test when appropriate. RESULTS: The percentage of wild-type allele bearers (?/?plus ?/D32 genotypes) in the preeclamptic group was significantly higher than that of non-bearers (98.6 vs.91.4%, P = 0.03, by the Fisher's exact test). The number of the individuals with D32/D32 genotype was significantly high in the control group (P = 0.035). D32 allele revealed a 2.3 fold protective effect against the risk of preeclampsia.When the percentage of G allele bearers of CCR5 59029A/G polymorphism was compared between the groups, a significant increase was seen in preeclamptics (P = 0.002). CONCLUSION: CCR5 polymorphisms significantly influenced the susceptibility to preeclampsia in our study population consisted of Caucasians. The role of chemokines in this syndrome appears to be an important issue. PMID- 22314436 TI - Tibial hemimelia-polydactyly-five-fingered hand syndrome associated with a 404 G>A mutation in a distant sonic hedgehog cis-regulator (ZRS): a case report. AB - Tibial hemimelia-polydactyly-triphalangeal thumb syndrome is a distinct congenital limb anomaly complex, whose association with the 404 G>A mutation in a distant sonic hedgehog cis-regulator (ZRS) was suggested. The authors report a sporadic case of bilateral tibial hemimelia-preaxial polydactyly-five-fingered hands harboring the same mutation. This case further supports a causal relationship between this mutation and the phenotype. PMID- 22314437 TI - Elevated serum gamma-glutamyltransferase associated with canine renal adenocarcinoma. PMID- 22314440 TI - Reward: High expectations for GABA. PMID- 22314443 TI - Understanding calcium waves and sparks in central neurons. AB - All cells use changes in intracellular calcium concentration ([Ca(2+)](i)) to regulate cell signalling events. In neurons, with their elaborate dendritic and axonal arborizations, there are clear examples of both localized and widespread Ca(2+) signals. [Ca(2+)](i) changes that are generated by Ca(2+) entry through voltage- and ligand-gated channels are the best characterized. In addition, the release of Ca(2+) from intracellular stores can result in increased [Ca(2+)](i); the signals that trigger this release have been less well-studied, in part because they are not usually associated with specific changes in membrane potential. However, recent experiments have revealed dramatic widespread Ca(2+) waves and localized spark-like events, particularly in dendrites. Here we review emerging data on the nature of these signals and their functions. PMID- 22314444 TI - Direction selectivity in the retina: symmetry and asymmetry in structure and function. AB - Visual information is processed in the retina to a remarkable degree before it is transmitted to higher visual centres. Several types of retinal ganglion cells (the output neurons of the retina) respond preferentially to image motion in a particular direction, and each type of direction-selective ganglion cell (DSGC) is comprised of multiple subtypes with different preferred directions. The direction selectivity of the cells is generated by diverse mechanisms operating within microcircuits that rely on independent neuronal processing in individual dendrites of both the DSGCs and the presynaptic neurons that innervate them. PMID- 22314445 TI - Speciation of mercury in the strongly polluted sediments of the Deule River (France). AB - The Deule River in Northern France experienced serious contamination from the metallurgical industry, especially from the smelter Metaleurop prior to 2003. In 2002 the surface sediments were collected from the bed of the river around 10 km above and 10 km below the smelter. Total mercury (HgT) and methylmercury (MeHg) concentrations exceeded the background value of 0.1 mg kg(-1). The average concentrations were 19.67 +/- 1.02 mg kg(-1) and 10.88 +/- 1.08 MUg kg(-1), respectively. In 2003 the sediment core samples were collected at two different sites near the factory for survey depth profiles of Hg contamination. The concentrations of HgT and MeHg in sediment cores varied from 10.47 to 259.44 mg kg(-1) and from 3.24 to 82.61 MUg kg(-1), respectively. The concentration of total mercury was significantly correlated with the methylmercury concentration in the sediment below a depth of 23.5 cm (R(2) = 0.81, p < 0.01). This may suggest that the production of MeHg is directly related to the HgT concentration. Nevertheless the MeHg/HgT ratio in the upper part of the sediment core was higher than that in the lower part. This suggests that HgT and MeHg may have been co deposited together. However, the methylmercury production takes place in the surface sediment by microorganisms. The strong correlation observed between MeHg and acid volatile sulfides (AVS) suggests that MeHg variability is associated with the bacterial activity (presence of AVS). PMID- 22314446 TI - Pattern of malignancy in clinically solitary thyroid nodule. AB - Solitary thyroid nodule (STN) is a common thyroid disorder. Clinically recognized thyroid carcinoma constitutes less than 1% of human malignant tumours. The risk of malignancy in solitary thyroid nodule is greater than other thyroid swelling. The risk of malignancy in generalized thyroid swelling is about 3% and in solitary thyroid nodule it is about 15%. This study was carried out in Surgery and ENT Department, Mymensingh Medical college Hospital from November 2008 to October 2009 to see pattern of malignancy in clinically solitary thyroid nodule. Total 108 patients of STN was included in this study, majority of the patients were within 20-39 years age group with female predominance. In addition to thyroid swelling some patients presented with other symptoms like cervical lymphadenopathy in 6(5.56%), dysphagia 2(1.85%), hoarseness of voice 2(1.85%) and metastatic lesion in bone 1(0.92%) cases. Among 108 cases of solitary thyroid nodule only 19 cases were malignant. Patients with malignant lesion presented with shorter duration of symptoms. Out of 19 malignant cases 6(31.58%) cases presented with features of metastasis. Malignancy was more predominant in male (25.00%) than the female (14.47%) in STN. Out of 19 malignant cases, 12(63.16%) were papillary carcinoma, 5(26.31%) were follicular carcinoma and 2(10.53%) cases were medullary carcinoma. Study showed significant difference (p<0.01) between papillary & follicular carcinoma and significant difference (p<0.001) between papillary & medullary carcinoma. Papillary carcinoma was most common among all thyroid malignancies in patients with solitary thyroid nodule. PMID- 22314447 TI - Non-culture diagnosis of Chlamydia trachomatis genital infection in sexually active women. AB - Infections caused by Chlamydia trachomatis (CT) are one of the most prevalent of all sexually transmitted diseases (STD). This cross sectional study was carried out to diagnose genital CT infection on 108 (59 pregnant and 49 non-pregnant) women attending at Department of Gynaecology and Obstetrics, Mymensingh Medical College Hospital (MMCH) during the period from January 2009 to December 2009. This non- culture technique was based on detection of CT major outer membrane protein (MOMP) by Direct Fluorescence Antibody Test (DFAT) from endocervical swab. Chlamydial inclusion bodies (IB) were looked for using Iodine stain. CT antigens were detected in 45.3% (49/108) cases by DFAT; IBs were detected in 5.5% cases (06/108) by Iodine staining technique. Majority of CT positive cases (65%) were found in the younger age group (15 to 25 years). The CT infection was found 47.2 % (35/74) in symptomatic cases, 41.1% (14/34) in asymptomatic cases and 47.4% in pregnant group, 42.8% in non-pregnant group. Although high incidence of genital chlamydia infection is common both in pregnant, non-pregnant, symptomatic and asymptomatic women in Bangladesh an early and reliable diagnostic method for genital chlamydia infection in Bangladesh should be further explored. PMID- 22314448 TI - Seasonal variation in types of stroke and its common risk factors. AB - The present descriptive cross-sectional study was conducted in the Department of Medicine, Mymensingh Medical College Hospital, Mymensingh, Bangladesh over a period of one year during November 2009 to October 2010. The study was conducted to describe the variations in types of stroke (ischemic stroke and hemorrhagic stroke) during summer and winter. An attempt was also made to observe the frequency of common risk factors of stroke by seasons. A total of 292 patients of any age irrespective of sex fulfilling the WHO criteria of acute stroke and confirmed by CT scan were selected from consecutive admission in the Department of Medicine, Mymensingh Medical College Hospital. Detail history and thorough clinical examinations were done. Routine and relevant investigations were carried out. The mean age of the patients was 59.9+/-14.3 years. A male preponderance was observed in the study. In summer 66% of patients and in winter 34% of patients were presented. Ischemic stroke was present in 54.1% patients and 45.9% patients had haemorrhagic stroke. The study found that the frequency of ischaemic stroke during summer (62.4%) was significantly greater than that during winter (37.8%). The frequency of haemorrhagic stroke during winter (62.2%) was significantly greater than that during summer (37.6%). Hypertension was the most important risk factor and other risk factors were smoking, diabetes mellitus, tobacco chewing, ischemic heart disease, dyslipidemia, oral contraceptive pill, alcohol consumption, atrial fibrillation and past history of stroke. Increasing age was also noted as a risk factor (60.7% >60 years). Most of the risk factors were homogenously distributed between two seasons and between ischemic and haemorrhagic group. Hypertension was significantly higher in haemorrhagic stroke patients compared to ischemic stroke patients. PMID- 22314449 TI - Nested polymerase chain reaction for early diagnosis of typhoid fever. AB - Typhoid fever, caused by Salmonella typhi, is an important cause of morbidity and mortality in many developing countries. A rapid and sensitive method for the detection of S. typhi is essential for early diagnosis. This was a study to prospectively evaluate the sensitivity and specificity of nested polymerase chain reaction (PCR) to identify the S. typhi using flagellin gene related primers. The study was carried out in the department of Microbiology, Mymensingh Medical College, Mymensingh between July, 2010 and June, 2011, including 82 individuals of different age and sex. Of them, 62 were clinically suspected cases of typhoid fever and remaining 20 were apparently healthy controls. Cultures as well as PCR of blood specimens were performed for each of the cases. Among the 62 suspected typhoid fever cases, 8(12.9%) were blood culture positive and 55(88.7%) were PCR positive for S. typhi. All culture positive cases were positive by PCR and among 54 culture negative cases, 47(87%) were positive by PCR. Neither of the healthy controls was positive by PCR or blood culture. The sensitivity, specificity, positive predictive value and negative predictive value of PCR using blood culture as gold standard were 88.7%, 100%, 100% and 74% respectively for typhoid fever. In this study, the PCR appears highly specific, very sensitive and superior to blood culture for the early diagnosis of typhoid fever. PMID- 22314450 TI - Clinical profile of periodic paralysis. AB - This cross sectional descriptive study was done to find out common clinical presentations, etiologies and laboratory investigation abnormalities in patients of periodic paralysis. Study was carried out in 30 patients with an age range from 8 to 70 years who were enrolled from July 2008 to June 2009 in Mymensingh Medical College Hospital (MMCH) medicine unit. Individuals who were admitted with sudden onset generalized muscle weakness, had history of previous attack and serum potassium level <3mmol/l or >5.5mmol/l were included in this study. In this series, majority of the patients were male (66.67%). Male: female ratio was approximately 2:1. The mean age of the patients was 27.4+/-4.5 years. Majority (26.67%) of them were in age range of 31-40 years. About 30% of the patients experienced the first attack of paralysis at the age of 20-24 years. Majority of patients (53%) were from middle class family with occupation of private service (26.66%) and farmer (20%). Positive family history was reported in 20% of patients. Regarding the precipitating factors, majority of patients (83.3%) were related to high carbohydrate meal, 56.67% related to temperature, 41.67% to exercise. Flaccid muscle weakness with variables muscle power (MRC grade 4/5 to 2/5 in 60% and 1/5 to 0/5 in 40%) was found. Cerebellar functions, all modalities of sensations and functions of cranial nerves were intact in all patients. In this series, laboratory investigations revealed reduced serum potassium level (<3mmol/l) in 90% of patients. Serum potassium value >5.5mmol/l was found in only 3.33% of patients. Creatine kinase (MM) was raised in 23% of the patients and Thyroid stimulating hormone (TSH) level was 0.8-2mmol/l in 6% of the patients. More than half of the patients (56%) showed variable ECG changes. Impaired nerve conduction function was found in 28.00%. So, careful history taking, meticulous clinical examination and simple laboratory investigations is sufficient to make a prompt diagnosis and rapid management of patients with periodic paralysis. PMID- 22314451 TI - Morphometry of seminiferous tubules of human testes in different age groups in Bangladeshi cadavers. AB - This cross sectional descriptive study was done to observe the mean diameter of seminiferous tubules and to determine its differences between different age groups in Bangladeshi male. Thirty human testes of different age groups were collected by purposive sampling technique. Among them 22 specimens were collected from cadavers during routine postmortem examination and 8 specimens were from dead fetuses from Gynaecology & Obstetrics Department. The specimens were grouped into three categories Group A (28 to 42 weeks of gestational age), Group B (Up to 14 years) and Group C (15 to 70 years). The mean diameter of seminiferous tubules was measured and significant differences of the dimensions between different age groups were determined. The mean+/-SD diameter was 85.37+/-15.51 MUm in Group A, 144.04+/-63.34 MUm in Group B and 227.92+/-22.47 MUm in Group C. Statistically, differences between age groups were calculated by using Unpaired Students 't' test. The present study revealed that the diameter increased with age and mean differences were statistically significant between Groups A&C, B&C and A&B. PMID- 22314452 TI - Histomorphometric study of lumen of human vermiform appendix. AB - This study was done to find out the histomorphometry of lumen of vermiform appendix in Bangladeshi people. Total 100 fresh appendixes were collected for morphometric study of different age and sex during postmortem examination in the autopsy laboratory of Forensic Medicine Department of Mymensingh Medical College. This cross sectional descriptive study was done by convenient sampling technique. For convenience of differentiating the luminal diameter of vermiform appendix in relation to age and sex, findings were classified in four groups. Group A was up to 20 years, Group B 21-35 years, Group C 36-55 years and Group D 56-70 years. In the study the maximum diameter was in group A of female (87.00 MUm) and minimum was (4.70 MUm) in group B of female. The mean luminal diameter of vermiform appendix was more in female (60.71 MUm) than in male (60.11 MUm). PMID- 22314453 TI - Correlation of triglyceride level with acute coronary syndrome. AB - The study was aimed to find out the correlation of serum triglyceride level with acute coronary syndrome. This cross sectional study was conducted in the department of cardiology, Mymensingh Medical College Hospital, from August 2009 to May 2010. Socio-demographic characteristics, smoking habit, hypertension, serum total cholesterol level, serum HDLc, Serum LDLc, TG level were important variable considered. A total number of 100 respondents consisted of 50 cases (patient) and 50 healthy persons (control). Investigations included ECG, cardiac enzyme (troponin I), FBS and lipid profile. The data were analyzed by computer with the help of SPSS. Chi-square Test, T-test & ANOVA test were used as test of significance. The mean level of TG in acute coronary syndrome (ACS) patients (cases) was 168.2+/-58.0 mg/dl and in control were 141.2+/-45.3 mg/dl. So serum TG level is significantly higher in patients with ACS (p=0.01). In multivariate regression analysis, there was a significant association of elevated TG with risk of ACS (relative risk) is the highest, compared with the lowest quarantile = 1.011; 95% confidence interval (CI = 1.002 - 1.020; P for trend = 0.01). The relation of TG level to HDLc was a strong predictor of ACS (RR in the highest) compared with lowest quarantile = 0.02; (95% CI = 0.003 - 0.173; P for trend <0.0001). The study revealed that high level of serum triglyceride is associated with ACS. Categorization of patients with ACS on the basis of TG level may be helpful for risk stratification and management. PMID- 22314454 TI - Clinical and angiographic profile of congenital anomalous origin of coronary arteries. AB - Coronary artery anomalies were found in 24(0.6%) patients undergoing coronary arteriography at University Cardiac Center, Bangabandhu Sheikh Mujib Medical University, Dhaka from 2004 to 2007. Of the 24 patient, 21(87.5%) had anomalies of origin and distribution and 3(12.5%) had coronary artery fistulae. Most coronary anomalies did not result in signs, symptoms or complications and usually were discovered as an incidental finding at the time of catheterization. Most of them were benign anomalies: i) separate origin of left anterior descending and circumflex from sinus of valsalva; ii) ectopic origin of circumflex from right sinus of valsalva; iii) Anomalous origin of left main coronary artery from right coronary artery; iv) anomalous coronary origin from ascending aorta; v) absent left circumflex; vi) double right coronary artery; vii) small coronary artery fistula. These anomalies may be associated with potentially serious sequelae such as angina pectoris, myocardial infarction, syncope, cardiac arrhythmias, congestive heart failure, or sudden death. In this study large coronary artery fistula was found as potentially serious anomaly. So coronary artery anomalies require accurate recognition for the appropriate management of the patients. PMID- 22314455 TI - Vecuronium and fentanyl requirement in abdominal surgery under combined epidural general anaesthesia and general anaesthesia alone. AB - Individual effect of epidural block and general anaesthesia is well established in the field of anaesthesiology. But adequate literature is yet not available to give decisive answer regarding the requirement of muscle relaxants and opioid analgesic when the two methods are combined together. In the present study, sixty patients, aged 18-50 years of both sexes with ASA (American Society of Anesthesiologists) grading I and II scheduled to undergo for major abdominal surgery were assigned randomly into two groups (30 in each group), where Group A received general anesthesia and Group B received combined epidural-general anesthesia. The patients with combined technique, epidural catheter tip were placed between T9-10. Ten ml of 0.125% bupivacaine was administered through the epidural catheter. Peripheral nerve stimulator was used to monitor neuromuscular transmission and subsequently to administer incremental dose of neuromuscular blocking drugs. All the patients were pre-medicated with fentanyl (2MUg/kg) to reduce intubation reflex. Then the patients of both groups were pre-oxygenated for 3 minute and anaesthesia was induced with thiopental sodium 3-5 mg/kg body weight. Endotrachial intubation was facilitated by vecuronium 0.1mg/kg body weight. Anaesthesia was maintained with 60% N2O in O2 and halothane (0.4 to 0.8%). Fentanyl was given in incremental dose of 0.5 MUg/kg to maintain an adequate analgesia. The vecuronium was given at the dose of 0.02 mg/kg, when TOF return to 25% of the base line. The mean+/-SD requirement of vecuronium in general anaesthesia group was 0.0016+/-0.00013 mg/kg/min and whereas in combined epidural-general anaesthesia, it was 0.0011+/-0.00014 mg/kg/min. The requirement of fentanyl was 0.71MUg/kg/hr in general anaesthetic group whereas in combined group it was 0.31MUg/kg/hr. These findings prompt us to place optimal dosing guidelines so as to avoid overdosing and thus delay recovery and help to get the excellent outcome of the surgery. PMID- 22314456 TI - Outcome of metformin treatment in polycystic ovary syndrome. AB - The polycystic ovary syndrome (PCOS) is a clinical diagnosis. During one year period, 50 women suffering from PCOS were treated with either 850 mg/twice daily or 500 mg/thrice daily along with clomiphene citrate and/or letrozole, with advice for exercise and dietary therapy. Diagnosis of the PCOS patients was made by the presence of two out of the following three criteria: (a) oligo and/or anovulation, (b) hyperandrogenism (clinical and/or biochemical), and (c) polycystic ovaries, with the exclusion of other aetiologies. The mean+/-SD age of our patients was 26.74+/-3.85 years, BMI 26.64+/-2.64 kg/m2, pulse 80.56+/-4.61 b/min, systolic blood pressure 113.80+/-4.40 mmHg and diastolic blood pressure 76.10+/-4.77 mmHg, duration of marriage 6.19+/-3.20 years, and parity was 43(86%) nulliparous and 7(14%) primiparous. Oligomenorrhoea was present in 100%, hypomenorrhoea in 38%, secondary amenorrhoea in 28% and acne in 70% women. Results showed that 92% women followed advice on exercise and dietary therapy, in maximum number of women progesterone level was 31.40 nmol/L (66%), weight loss was 2 kg (44%), menstrual cycle regular (90%) and pregnancy test negative (90%). Only in 5 cases (10%) pregnancy test was positive. PMID- 22314457 TI - Efficacy of salbutamol by nebulizer versus metered dose inhaler with home-made non-valved spacer in acute exacerbation of childhood asthma. AB - This study was done to evaluate and to compare the efficacy of jet nebulizer and metered dose inhaler (MDI) with home-made non-valved spacer (HM NVS) to deliver aerosolized salbutamol in acute exacerbation of asthma in children. HM NVS was made by 500ml plastic mineral water bottle. It was perforated at the bottom for the insertion of MDI and proximal end was cut for placing the mouth. This prospective randomized study was conducted in the department of Pediatrics, Dhaka Medical College Hospital, during April 2007 to March 2008 with 50 known cases (2 12 years) of bronchial asthma with acute exacerbation. After randomized enrollment, each patient received three doses of salbutamol either through a jet nebulizer or through a HM NVS. Oxygen saturation (SaO2), wheeze, heart rate, respiratory rate were recorded throughout the treatment period. Data were analyzed with SPSS for Windows 10.0 at p value <0.05 was considered significant. The mean age of patients was 59.8 months in nebulizer group versus 69.4 months in MDI with HM NVS group. Baseline clinical characteristics in nebulizer group were SaO2 87.7+/-2.5 versus 89.0+/-1.8 percent, RR 59.2+/-7.3 vs. 63.2+/-4.8 per minute, HR 155.4+/-11.8 versus 149.0+/-10.8 per minute and wheeze in 22(88.0%) cases versus 21(84.0%) cases respectively (p>0.05). After therapy improvement was noted among the nebulizer group (SaO2 87.7+/-2.5 vs. 94.3+/-2.8 percent; RR 59.2+/-7.3 vs. 39.3+/-4.9 per minute; HR 155.4+/-11.8 vs. 151.60+/-17.3 per minute; wheeze 88% vs. 8%) as well as in the MDI with HM NVS group (SaO2 89.0+/ 1.8 vs. 94.8+/-1.8 percent; RR 63.2+/-4.8 vs. 38.7+/-6.4 per minute; HR 149.0+/ 10.8 vs. 144.5+/-13.5 per minute; wheeze 84% vs. 16%) [p<0.001; CI:95%]. However, these improvements did not differ significantly between the nebulizer group and HM NVS group (SaO2 94.3+/-2.8 vs. 94.8+/-1.8 percent, RR 39.3+/-4.9 vs. 38.7+/ 6.4 per minute, HR 151.60+/-17.3 vs. 144.5+/-13.5 per minute and wheeze persisted in 2(8.0%) cases versus 4(16.0%) cases respectively) [p>0.05]. The overall response to these modalities of treatment was satisfactory in nebulizer (19/25) and HM NVS (17/25). Salbutamol delivered through both nebulizer as well as MDI with HM NVS is equally effective in the treatment of acute asthma in children. PMID- 22314458 TI - Effect of pre-bypass methylprednisolone on post-operative renal function following correction of atrial septal defect under cardiopulmonary bypass. AB - Conventional open heart surgery with cardiopulmonary bypass (CPB) are associated with transient post-operative renal dysfunction which is caused by systemic inflammatory response induced by CPB. Corticosteroids are administered to attenuate the systemic inflammatory response. The purpose of this study was to compare the effects of pre-bypass and post-bypass methylprednisolone on postoperative renal function after correction of ASD under CPB. Forty (40) patients were selected in the University cardiac centre of BSMMU undergoing ASD correction under CPB. Patients were randomized into two group to receive pre bypass (Group A) or post-bypass (Group B) methylprednisolone 30mg/kg. Markers of glomerular function (BUN, serum creatinine, creatinine clearance) and damage (micro-albuminuria) and tubular function (glucosuria) were evaluated 24 hours after operation. Transient impairment of glomerular and tubular function of kidney was observed in patients those received post-bypass metylprednisolone (Group B) while Group A patients shown no significant difference between baseline and post-operative renal function. Use of pre-bypass methylprednisolone has a protective effect on post-operative renal function after correction of ASD under CPB. PMID- 22314459 TI - Association of Helicobacter pylori infection and gastric carcinoma. AB - Gastric carcinoma is a worldwide disease, representing the second most frequent cancer in the world. Gastric carcinogenesis is a multifactoral process and it results from interaction of the several factors that are related to diet, environment, genetic susceptibility, and Helicobacter pylori (H. pylori) infection. Many evidence showed that H. pylori, the important pathogen for a wide spectrum of gastro duodenal diseases. Substantial epidemiological evidence exists for an increased risk of gastric carcinoma with H. pylori infection. This study was conducted with the objective to find out an association of H. pylori infection and gastric carcinoma in a Bangladeshi population. This case-control study was conducted between June 2003 and July 2004, in the department of Surgery in joint collaboration with department of Pathology and Department of Microbiology and Immunology in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. A total number of 151 subjects were included in this study. Fifty gastric carcinoma patients were considered as cases and 101 control subjects were selected from the admitted patients in the surgical ward having no gastric cancer, but with other gastro duodenal disorders. The mean age+/-SD among the cases and controls were 51.84+/-12.69 and 35.08+/-11.67 years respectively. Among the 50 cases 36(72.0%) and among the 101 controls 74(75.3%) were male. The male and female ratio among the cases and controls were 1:0.39 and 1:0.36 respectively. Among the 50 cases 40(80.0%) and among the 101 controls 62(61.4%) were serologically positive for H. pylori infection. Difference of H. pylori infection in both study groups were evident and statistically significant (OR=2.516, p<0.05). It may be concluded from this study, H. pylori infection may be associated with gastric carcinoma. PMID- 22314460 TI - Early diagnosis of neonatal septicemia by hematologic scoring system, C-reactive protein and serum haptoglobin. AB - Neonatal septicemia is one of the major health problems throughout the world. Infections are frequent and important cause of morbidity and mortality in neonatal period. The objective of the present study was to find out the role of hematologic scoring system (HSS), C-reactive protein (CRP) and haptoglobin in the early diagnosis of neonatal septicemia. This is a descriptive consisted of 100 neonates admitted at neonatal ICU, BSMMU, who were clinically suspected sepsis. The hematological parameter, C-reactive protein and haptoglobin were measured in all cases. Blood culture was done as the gold standard for diagnosis of neonatal septicemia. There were 12 out of 100 neonates (12%) who had culture proven sepsis and they were predominantly preterm and very low birth weight. On evaluation of various hematological parameters total leukocyte count, total neutrophil count, immature to total neutrophil ratio (>0.2), immature to mature neutrophil ratio (>0.3), total immature count, platelet count were found to have optimal sensitivities and negative predictive values. Using these values hematologic scoring system (HSS) was formulated according to Rodwell et al. Score >=4 was found sensitivity of 100%, specificity of 60%. C-reactive protein (CRP) had sensitivity of 75%, specificity of 74%. Haptoglobin was not found significant (p<0.05) with sepsis and sensitivity was very low. But Combination of score >=4 and CRP showed sensitivity of 75%, specificity 85%, positive predictive value (PPV) 41% and negative positive value (NPV) 96%. HSS and CRP are useful test to differentiate the septicemic from non septicemic neonates and also provide a effective guideline to make decisions regarding judicious use of antibiotic therapy. But haptoglobin level was not found useful for screening of sepsis. PMID- 22314461 TI - Melphalan plus prednisolone in the treatment of multiple myeloma. AB - Various chemotherapies are used for better remission of symptoms of multiple myeloma as it is not a curable disease. This study was carried out to evaluate the response of melphalan plus prednisolone therapy for the treatment of Multiple myeloma. The study was conducted in the outpatient department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from January to December 2009. A total of 21 patients were included in this study. Combinations of melphalan plus prednisolone were given. Data were analyzed by paired 't' test to evaluate the response after treatment. Most of the patients were within 40-60 years with a male predominance. Haemoglobin level significantly raised after therapy (p<0.001) and ESR was found significantly reduced of these patients after treatment (p<0.001). On the other hand no significant change seen in calcium level before & after therapy (p=0.713). Significantly raised albumin and B2 microglubulin level were also found after treatment (p<0.001). After therapy with malphalan plus prednisolone, 11(52.38%) patient's M Protein reduction was >75%, 7(33.33%) patients M Protein reduction was 50-75%, 1(9.5%) patient's M Protein reduction was >25-50% and 1(12.50%) patient's M Protein reduction was <25%. Mean+/-SD M protein values before & after therapy were 50.23+/-19.49 gm/l and 21.01+/-16.11 gm/1 respectively. M protein level significantly reduced after treatment (p<0.001). PMID- 22314462 TI - Comparative study of total prostate specific antigen and free to total prostate specific antigen ratio in the diagnosis of prostate cancer. AB - This descriptive study was done to compare total Prostate Specific Antigen (tPSA) and the Free to Total Prostate Specific Antigen [(F/T) PSA] ratio measurements for prostate cancer detection. This study included a total of 43 patients with suspected prostate cancer observed over a period of 12 months. Out of 43 consecutive male patients (mean age 69+/-9.39 years, range 48-100 years), 32 had benign disease (74%) and 11 had prostate carcinoma patients (26%), who had histologically proven prostate cancer. The mean total PSA was 67.9 ng/ml and 12.4 ng/ml in patients with carcinoma prostate and nodular hyperplasia of prostate (NHP) respectively (p<0.05). The mean free PSA in carcinoma patients was 7.4+/ 9.8 ng/ml and in NHP patients it was 2.3+/-4.1 ng/ml. The difference in mean free PSA concentration was significant (p<0.05). The free to total PSA ratio in two groups was significantly different (p<0.01) from each other. In carcinoma patients, mean F/T PSA ratio was 0.144+/-0.152 as compared 0.328+/-0.076 in patients with benign disease. The sensitivity and specificity of the test was calculated at different F/T PSA ratio cutoff. At 0.1 cut off value, sensitivity of the test was 64% and specificity was 84%. The positive predictive value (PPV) was 58% and negative predictive value (NPV) was 87%. From cutoff value of 0.12 to 0.16, sensitivity was increased from 64% to 91% but specificity was reduced from 84% to 59%. The PPV did not show much change and NPV was increased from 89% to 95%. Increasing the cut off value thereafter showed no change in sensitivity but specificity was further reduced to 41%. Therefore in this patient, F/T PSA ratio cut off of 0.15 was found to be the appropriate cutoff value. In 43 men who were biopsied, 11(26%) prostatic carcinoma were identified. Only one patient (9.1%) had F/T PSA ratio above 0.15 and diagnosed by biopsied. Out of 32 patients who were negative for malignancy, 13 patients had F/T PSA ratio more than 0.15 and 19 patients had F/T PSA ratio less than 0.15. The validity of tPSA and F/T PSA ratio in the diagnosis of prostate cancer was identified by calculating their sensitivity, specificity, PPV and NPV. In case of F/T PSA ratio the sensitivity was 91% and in conventional tPSA the sensitivity was 82%. Specificity was low in both the cases. But in tPSA the specificity was only 13% compare to 59% in F/T PSA. Positive predictive value (PPV) for tPSA was 25% and in F/T PSA it was 44%. Negative predictive value (NPV) for t PSA was 67% and for F/T PSA was 95% which was very high. The effectiveness of F/T PSA ratio at 0.15 cut off value with corresponding tPSA>10ng/ml shows sensitivity 83% in prostate cancer and 50% in NHP patient. PMID- 22314463 TI - Postnatal development of renal function in preterm and term neonates. AB - The study was done to determine the renal function in preterm and term newborn infants in the neonatology unit of the Department of Paediatrics and Labour Ward of the Department of Obstetrics and Gynaecology, Bangabandhu Sheikh Mujib Medical University (BSMMU) during the period of February 2002 to February 2003. Sixty physiologically stable newborn infants were enrolled in this study, 40 of those were preterm and 20 were term. The gestational ages of preterm and term babies were 35.6+/-4.7 and 39.10+/-1.41 weeks respectively. Mean weight of preterm babies was 1840+/-410 gm and term babies was 3150+/-340 gm respectively. Male to female ratio was1.6:1. The concentration of serum creatinine was high during the first week of life in both the term and preterm babies. The concentration decreased in both the groups during the subsequent 3 weeks. Although creatinine values were significantly high in preterm babies than the term babies at first week (p<0.001), the values reach to almost similar at 3rd week of life. A negative correlation was found between serum creatinine and gestational age (r=0.86, p<0.001). Creatinine clearance was found low at birth, the lowest values being observed in the most premature infants (p<0.0001) and was increased in the subsequent 3 weeks of the study period. Creatinine clearance showed a positive correlation to gestational age from the first week onwards (r=0.87, p<0.001). Fifteen percent preterm babies were hyponatraemic and in all term babies serum level of sodium was within normal limit. Fractional excretion of sodium was high in preterm neonate than the term neonate especially in early weeks of life (p<0.001). The value correlated negatively to gestational age (r=0.67, p<0.001). It was evident from the present study that the renal function is significantly lower in preterm neonates than term neonates. The study also indicates that the maturation of renal function occurs earlier in the term babies than the preterm babies. PMID- 22314464 TI - Antibody titre against 3 doses of hepatitis B vaccine among preterm and term babies. AB - This cross sectional study was conducted to assess seroprotection by completed 3 doses of hepatitis B vaccine in routine EPI schedule in preterm & LBW as well as term appropriate weight babies and to compare the immune response among them. The study was conducted in EPI centre of Dhaka Medical College Hospital where 50 preterm (<37 completed weeks of gestation) and low birth weight (<2500 gm) infants enrolled in group A and 50 term (37-42 completed weeks of gestation) appropriate weight (>=2500 gm) in group B. All infants were immunized with 3 doses of hepatitis B vaccine according to EPI schedule and first vaccine was given at 6 weeks after birth and subsequent doses are given at one month interval. Adverse events were monitored. Anti HBs titre was determined 1 month after 3rd dose of vaccine from serum by ELISA method (VITROS anti HBs reagent pack). Seroprotectivity (anti HBs titres >10 mIU/ml) of hepatitis B vaccine after 3 doses were 94% and 98% in group A and B respectively (p>0.05). However, the preterm infants had a lower geometric mean titre of antibodies after 3 doses of vaccine than did the term infants (92.75 mIU/ml vs. 310.59 mIU/ml respectively; p<0.001). After 3 doses of hepatitis B vaccine though the seroprotective anti HBs titre (i.e. >10 mIU/ml) was ~96% irrespective of gestational age and birth weight but good antibody titre (i.e. >100 mIU/ml) was found among preterm babies having gestational age >34 weeks (73.6%) and birth weight >2000 gm (64%). PMID- 22314465 TI - Response of vincristine, melphalan, cyclophosphamide and prednisolone in refractory multiple myeloma. AB - In refractory and relapsing multiple, myeloma good complete response rates may be achieved by Vincristine, Melphalan, Cyclophosphamide and Prednisolone (VMCP) like regimen which is effective alternative and less expensive in developing country like Bangladesh. The study was conducted to see the response of VMCP as an alternative in relapsing or refractory multiple myeloma. The study has been carried out in the department of Haematology, Bangabandhu Sheikh Mujib Medical University from July 2004 to June, 2005. This study was conducted on refractory case of multiple myeloma, having aged between 45 to 70 years. A total of ten patients had been taken for this study group. Newly diagnosed multiple myeloma is not included in this study. All of the 10 patients were treated according to the following VMCP protocol, Vincristine 1mg IV, d1, Melphalan 6mg/m2/d p.o. d1-d7, Cyclophosphamide 120mg/m2/d p.o. d1-d7 Prednisolone 60mg/m2/d p.o. d1-d7. Cycles were repeated every 28 days for 6 cycle. Six out of ten patients with refractory multiple myeloma displayed minimal response (60%) after treatment with 6 cycle of VMCP protocol, three patients entered partial remission (30%), and one (10%) showed complete response. PMID- 22314466 TI - Clinical, biochemical and virological profile of chronic hepatitis B virus infection in children. AB - Hepatitis B virus infection is prevalent worldwide. Overall prevalence is about 3 percent in Bangladesh. This prospective study aimed to find out the clinical, biochemical & virological profile of chronic HBV infection in children. It was conducted on patient attending the Department of Paediatric Gastroenterology and Nutrition of Bangabandhu Sheikh Mujib Medical University. A total of 90 cases were studied from October 2007 to October 2009. Univariate analysis was done. The study showed that most of the patients of chronic HBV are clinically asymptomatic, biochemically normal or near normal. Most of the chronic HBV infected patients are virologically HBeAg positive (77.8%). Therefore screening for asymptomatic HBV infection is essential for early diagnosis and treatment. PMID- 22314467 TI - Androgen versus erythropoietin for the treatment of anaemia of pre-dialysis chronic kidney disease. AB - Chronic kidney disease is a microvascular complication of diabetes mellitus (DM). Anemia is an important clinical manifestation to treat chronic kidney disease. Many subjects with poor socio-economic status having chronic kidney disease (CKD) and anaemia in a developing country can not afford the treatment with erythropoietin. This study has designed to see the efficacy of Nandrolone, a cheaper alternative; in comparison with recombinant human erythropoietin for management of anemia of pre-dialysis diabetic chronic kidney disease. Sixty adult diabetic patients with anaemia of chronic kidney disease on conservative treatment [Not on Hemodialysis (HD)] were enrolled. Patients were divided into two groups (Group 1 and Group 2) of 30 patients each. Group 1 patients received nandrolone deaconate 50 mg deep intramuscular and Group 2 recombinant human erythropoietin 100 IU per kilogram of body weight subcutaneously once weekly. Patients of both group received oral supplements in order to maintain body iron stores. All the relevant haematological and renal parameters were evaluated at the end of 3rd & 6th months. There was a statistically significant rise in haemoglobin concentration, packed cell volume, in both groups. The rise in haemoglobin concentration, in Group 2 was more marked followed by Group 1, at the end of 3rd, and 6th months. Nandrolone, though not equally effective, may be considered as a valid alternative therapy for the treatment of anemia of pre dialysis diabetic chronic kidney disease to that of erythropoietin. PMID- 22314468 TI - Prevalence of diabetes among hypothyroid subjects. AB - Thyroid dysfunction affects a significant portion of the general population. Most studies have found a higher prevalence of hypothyroidism in women, increasing with age. Prevalence of hyperthyroidism has been found to range 0.5-3.0%. Type 2 diabetes is a major public health problem affecting approximately 4.8 percent of the Bangladeshi population. The study was designed to see the prevalence of type 2 diabetes in hypothyroid patients of any etiology. Four hundred forty two consecutive cases of diagnosed hypothyroidism were recruited in the study. All diagnosed hypothyroid subjects (sub-clinical or overt) reported in one year not known to be diabetic previously, underwent standard OGTT (FPG and 2-hour post 75 gram glucose) before initiation of thyroid hormone replacement. Newly detected diabetes among the subjects diagnosed as hypothyroidism is significantly higher 4.8 vs. 7.01% (p<0.01) and the prevalence of pre-diabetic state Impaired Glucose Tolerance (IGT) is also higher (11% vs. 12.6%) among hypothyroid subjects. Pure IFG (FPG >=6.1 mmol/l but <7.0 mmol/l, and 2-PG <7.8 mmol/l) was found in 5.2% according to WHO criteria and the prevalence is higher (6.8%) with ADA criteria (considering normal FBG <5.6mmol/l). Diabetes was found in 7.01% among hypothyroid subjects which is higher than the existing known prevalence (4.8%). IGT was also found higher among hypothyroid subjects than population prevalence (8.6%). Further larger sample study is essential to establish the findings. PMID- 22314469 TI - Structural lesion in the brain is a risk factor of childhood intractable epilepsy. AB - Most of the intractable epilepsy cases are of paediatric age group. Eighty per cent of intractable epilepsy is symptomatic and have got structural lesion. These lesions are easily detectable by doing neuro-imaging. One hundred and four children with epilepsy were enrolled in two groups; in group A 52 intractable epilepsy patients and in group B 52 well controlled epilepsy patients from the child neurology unit of Bangabandhu Sheikh Mujib Medical University. Mean age of intractable group and well-controlled group was 4.45+/-3.66 years and 6.45+/-5.24 years respectively. Male were more in both groups. Abnormal neuro-imaging was significantly higher in intractable group; 78.8% children of the intractable epilepsy group had one or more structural lesions. Cortical atrophy, ventricular dilatation and encephalomalacia were the most frequent detectable lesions. Bilateral lesions and presence of multiple abnormalities were more in association with intractability. Structural lesions were detected more in cases with focal neurological deficit and structural abnormality having statistically significant difference. PMID- 22314470 TI - The tocolytic role of nifedipine in preventing preterm labour pain. AB - This study was undertaken to evaluate the efficacy of oral nifedipine to reduce labour pain in patient with preterm labour, to complete the doses of steroids in lung maturity and in utero transfer to the Neonatal Intensive Care Unit (NICU) and to evaluate the maternal adverse effects and neonatal outcome. Diagnosed cases of preterm labour (between 24 to 34 weeks gestation) were randomly selected. Among them 50 patients were given oral nifedipine (n=50) and 50 patients were observed with no treatment (n=50). There were no statistically significant differences in age, race, parity, preterm delivery risk factor between the groups. At first the labour pain were observed through Continuous CTG in first hour, then intermittent CTG. The patient in the Nifedipine group can prolong the pregnancy time 36.0+/-3.2 wks than 30.6+/-3.1 wks in the control group (p<0.05) with reduced neonatal complications and admission to NICU. Oral nifedipine in patients with preterm labour pain as Tocolytic therapy has significantly prolonged pregnancy with lesser neonatal problems and fewer maternal adverse effects. PMID- 22314471 TI - Comparative study between Pap smear and visual inspection using acetic acid as a method of cervical cancer screening. AB - This prospective study was done for the comparison of visual inspection using acetic acid (VIA) and Pap smear as a method of cervical cancer screening. This study was also done to determine the proportion of women screened positive with VIA and proportion of women screened positive with Pap smear. Another aim was to compare the sensitivity and specificity of VIA and Pap smear. A total of 300 women attended to the outpatient gynecologic clinic and cervical cancer screening programme at Bangabandhu Sheikh Mujib Medical University (BSMMU) were included. On VIA, 23 out of 300 women screened had aceto-white lesions. On Pap smear, 14 out of the 300 women had ASCUS or worse lesions. Of the 300 enrolled women, 11 were positive on both VIA and cytology; 12 were positive on VIA only; and 3 were positive on cytology only. Those women (n=26) who showed positive test result with either VIA or Pap smear or both tests were further subjected to colposcopy directed biopsy. Histology was taken as gold standard to compare the performance of VIA and cytology (Pap's smear). Histological diagnosis of CIN/cancer was made in 18 Positive cases out of the total 26 patients who underwent biopsy. Pap smear picked up 10 out of the 18 biopsy-proven cases whereas VIA could identify 17 out of the 18 CIN/carcinoma cervices. VIA was more sensitive (94.44%) than pap smear (55.55%), which was statistically significant. However, the specificity of VIA was slightly lower (97.87%) than that of cytology (98.58%). The PPV of VIA was 73.91% versus 71.42 % for Pap smear. PMID- 22314472 TI - Prevalence of cleft lip and cleft palate in a tertiary hospital in Eastern Nepal. AB - The aim of this investigation was to determine the birth prevalence of cleft lip and palate in a tertiary health care centre of Dharan, Eastern Nepal and to ascertain whether the birth prevalence in this region differs significantly from birth prevalence reported in similar populations and other racial groups. A retrospective study was conducted from June 2005 to December 2010. The maternity records which included a record of the examination of the newborn child for the prescribed period were analyzed. Fifty one clefts were identified among 30,952 live births during 2005 to 2010. The total birth prevalence of cleft of the lip +/- cleft of the palate (CL+/-P) was 1.64/1000 live births per year. There were 19 clefts of the lip alone (birth prevalence 0.61/1000 per year), 21 cleft lip and palate (0.67/1000 per year), and 11 cleft palate only (0.35/1000 per year). The birth prevalence was higher than what is reported for Caucasian and African populations. Cleft of the lip and palate (CLP) was the most common pattern followed by cleft of the lip (CL) and cleft of the palate (CP). Overall there was a male predominance whereas individually CLP and CL were more common in males while CP was more common in females. PMID- 22314473 TI - Usher syndrome. AB - A young girl of 10 years age came from Nalitabari, Sherpur was admitted in the department of Ophthalmology, Mymensingh Medical College Hospital, Mymensingh on the 5th January 2011 with the complaints of dimness of vision of both eyes, night blindness and profound deafness since birth. She had parental history of consanguineous marriage. Best corrected visual acuity of this patient was recorded 6/60 both the eyes with nystagmus. Fundus examination showed waxy pallor optic disc, arteriolar attenuation and bony spicule pigmentation both eyes. By history and clinical examination the patient was diagnosed as Usher syndrome. PMID- 22314474 TI - Difficulty in diagnosis of nasopharyngeal carcinoma. AB - Due to difficult anatomical position nasopharyngeal carcinoma (NPC) is always challenging problems both from the diagnostic and therapeutic corner. A 24 years old lady came to our Department of Otolaryngology and Head-Neck Surgery with the complaints of epistaxis, right sided neck swelling, nasal obstruction and headache. On digital palpation Nasopharyngeal mass was found. We took biopsy from nasopharynx under indirect vision but report was not conclusive. Then we did CT scan, nasendoscopy. Nasendoscopy showed bilateral ethmoidal polyp with nasopharyngeal mass. We took biopsy from the nasopharyngeal mass and confirmed the diagnosis. PMID- 22314475 TI - Invasive ductal carcinoma in a young male breast. AB - Carcinoma arising in the male breast is a rare occurrence. The risk of male breast cancer increases with age, and the median age of diagnosis for men is 10 years later than that for females (67 to 71 years). Because of the absence of lobules in the normal male breast, lobular carcinoma cases are seen infrequently. All of the microscopic types identified in the female breast have been encountered in male but the most frequent is invasive ductal carcinoma and less frequent is invasive lobular carcinoma. We present the case of a 20 years old man presenting with a left breast lump. After left mastectomy with level 2 axillary clearance, histopathological examination revealed infiltrating ductal carcinoma. Our case represents ductal carcinoma in a proven genotypic young male patient showing no exogenous or endogenous estrogens exposure. PMID- 22314476 TI - Hepatic hydatid cyst presenting as cutaneous abscess. AB - Hydatidosis is a parasitic zoonotic echinococcal infection that affects both humans and other mammals. These diseases are common worldwide but particularly common in sheep and cattle farming regions. Anaphylaxis mediated by IgE is a serious complication of surgery or trauma which necessitates more aware of its clinical features, diagnosis and management. It is important to make a preoperative diagnosis based on the typical image findings, so that particular precaution can be taken not to rupture the lesion. A woman presented with a right upper quadrant cutaneous abscess. USG reveals multiple cystic lesions in the liver arranged in cartwheel appearance, CT disclosed a cystic lesions having daughter cysts, marginal calcifications, marginal enhancement and contiguous abdominal wall abscess, which led to a diagnosis of complicated hepatic hydatid cysts with abdominal wall abscess formation. FNAC showed scolices surrounded by chronic inflammatory cells. Abdominal wall abscess may be a presentation of hydatid liver disease. PMID- 22314477 TI - 17beta-hydroxysteroid dehydrogenase-3 deficiency in disorder of sex development. AB - A 29 years old patient, claimed to be a male, presented to us with pubertal gender swing from female to male. Since birth he was reared as a female child. His breasts, axillary hairs and pubic hairs developed at about 11-12 years of age. At that time he also observed the mental and physical changes towards a male. He began to feel sexual attraction towards females due to enlargement of his phallus and he preferred to behave as a male. The patient further noticed deepening of voice as well as appearance of facial hairs at about 15 years of age. He never experienced menstruation. His parents are first degree cousins. On examination, there was facial hairs in upper lip and chin (G3), breasts were in mature stage (B5), pubic hairs were darker, coarser and curlier and spreading sparsely (P3), and stretched dorsal phallic length was 6cm. In perineoscrotal area, there was hypospadias with blind vaginal pouch, partially fused, pigmented & ruggated bilateral labio-scrotal folds and soft palpable ellipsoid gonads measuring about 8 ml (each) in volume within labio-scrotal folds. Ultrasound examination revealed no uterus and karyotyping test found 46XY. Provisionally, he was diagnosed as a case of 46,XY Disorders of Sex Development (DSD). On further investigations, serum testosterone was low, serum LH and DHEA were raised and serum electrolytes were normal. From history, physical examination and investigations we diagnosed the case as 46,XY DSD due to 17beta-hydroxysteroid dehydrogenase-3 deficiency. PMID- 22314478 TI - Pulmonary metastases of a papillary adeno-carcinoma of ovary in a pregnant lady. AB - A 28 years young lady admitted to National Institute of Diseases of Chest and Hospital (NIDCH), Dhaka with the complaints of respiratory distress and cough for 2 months. She was in her last trimester of first pregnancy when she becomes dyspneic on exertion and at night. Gradually it increases in time and she become unable to walk when she consulted with specialists in Barisal. She was examined clinically and radiographically and found some opacity on both lung fields. She was on several antibiotics, but got no improvement. In the meantime, an emergency caesarean section was done to have a healthy baby and patient came to NIDCH for this unexplained breathlessness and cough. She was severely dyspneic, tachypnoic, cyanosed. There were bilateral coarse crepitations, bilateral opacities predominantly on both lower and middle zones of both lungs obscuring costo phrenic angles on chest X-rays. CT scan of chest shows bilateral reticulo-nodular shadows with a homogenous opacity on right lower lung which enhances after contrast scanning. A CT guided FNAC was done from that opacity which revealed a papillary adeno-carcinoma with psammoma bodies on cytopathological study. Thereafter, to explore the primary site, thyroid gland, abdominal organs was assessed adequately and only positive finding was raised CA-125 (706 IU/ml) which was consistent with ovarian cancer. In this way, a primary ovarian carcinoma in a pregnant young lady with normal sized ovary that metastasizes to lung causing bilateral pleural effusion and lymphangitis carcinomatosa was explored. This was an unusual presentation of ovarian papillary adeno-carcinoma with cough and breathlessness at the last trimester of pregnancy in absence of any abdominal mass. PMID- 22314479 TI - Juvenile onset ankylosing spondylitis with ankylosing tarsitis: a rare combination. AB - Ankylosing spondylitis is the most common whereas ankylosing tarsitis is the least common subgroup of juvenile onset spondyloarthritides. In our recent study a male presented with ankle joint pain and swelling with limited movements and characteristic radiological changes including; periarticular swelling, thickened heel pad, hyperostosis and reduced ankle, calcaneo-cuboid and talo-navicular joint space for ankylosing tarsitis. He also had persistent inflammatory low back pain with radiological sacroilitis satisfying the clinical features for ankylosing spondylitis. The patient was treated with different anti-inflammatory agents including intra-articular methyl-prednisolone with short-term relief. Associated back pain was improved with spine mobilizing exercise. PMID- 22314480 TI - Von Hippel-Lindau disease in a pregnant lady. AB - Von Hippel-Lindau disease is a rare genetic disorder characterized by various tumours and cysts in the central nervous system and other viscera. Here a case was described in a young female who was pregnant at the time of initial presentation with the complaints of occasional headache, low back pain and pain in the upper abdomen. After the birth of a healthy baby she was admitted to the hospital and the CT scan of upper abdomen suggested a multiloculated pancreatic cyst. MRI of thoracolumbar spine revealed an intracanalicular extradural mass and CT scan of brain revealed a cerebellar cystic mass. The spinal and cerebellar masses both were diagnosed histologically as haemangioblastoma. After a month she underwent laparotomy with near total pancreatectomy. Microscopically it was a microcystic cystadenoma. Based on the clinical presentation, imaging and histopathology of spinal, cerebellar and pancreatic lesions as well as a family history of her father's death due to brain tumour the final diagnosis was Von Hippel-Lindau disease. PMID- 22314481 TI - Autism spectrum disorder and detection of autism. PMID- 22314482 TI - Vertical concentration gradients of volatile organic compounds in two NS-oriented street canyons. AB - Diffusive samplers were used to measure the vertical concentrations of benzene, toluene, n-hexane, cyclohexane, ethylbenzene and o-, m- and p-xylenes on both sides of two NS-oriented street canyons in Murcia (Spain) during a 5-day period. Non-dimensional relationships of concentration and height were calculated in order to study the behaviour of their concentration vertical profiles. The results show that the vertical profiles of benzene, toluene, n-hexane and cyclohexane concentrations were similar in both streets and on both sides of each street. Some differences were found in vertical profiles between streets and sides for ethylbenzene and xylenes, probably due to their higher affinity for adsorption into building materials. The similarities found for the first set of VOCs suggest that the dynamics of the dispersion was the same for both streets and was mainly influenced by microscale thermal effects. Finally, the concentration measurements of benzene, toluene, n-hexane, cyclohexane, and ethylbenzene were adjusted to expressions in the form c = c 0(h/h 0) A , and a regression coefficient R 2 = 0.962 (p = 0.0000) was obtained. The decreasing concentration of these compounds with height should be taken into account when assessing population exposure to these pollutants. PMID- 22314483 TI - Drosophila is flying in China. PMID- 22314484 TI - Functional study of hyperpolarization activated channel (Ih) in Drosophila behavior. AB - Hyperpolarization-activated, cyclic nucleotide-gated and cation-nonselective ion channels (I ( h ) channels, or HCN channels) are known to play important roles in mammals. Their physiological functions in invertebrate remain largely unclear. Here, we report our studies with I ( h ) channel in Drosophila melanogaster. Drosophila Ih channel mutants are found with several defects by behavioral analyses. Their lifespan is reduced, and their chemical sensitivity is shifted. In addition, their length of sleep at light-dark condition is mildly reduced. We generated transgenic flies of I ( h ) promoter-driven Gal4 and examined its expression pattern in both larvae and adult flies. Our results suggest that I ( h ) channel may play diverse roles in Drosophila and provide a basis to further expand our understanding of Drosophila Ih channel function in vivo. PMID- 22314485 TI - Innate preference in Drosophila melanogaster. AB - Innate preference behaviors are fundamental for animal survival. They actually form the basis for many animal complex behaviors. Recent years have seen significant progresses in disclosing the molecular and neural mechanism underlying animal innate preferences, especially in Drosophila. In this review, I will review these studies according to the sensory modalities adopted for preference assaying, such as vision, olfaction, thermal sensation. The behavioral strategies and the theoretic models for the formation of innate preferences are also reviewed and discussed. PMID- 22314486 TI - Roles of chromatin assembly factor 1 in the epigenetic control of chromatin plasticity. AB - Genetic information embedded in DNA sequence and the epigenetic information marked by modifications on DNA and histones are essential for the life of eukaryotes. Cells have evolved mechanisms of DNA duplication and chromatin restoration to ensure the inheritance of genetic and epigenetic information during cell division and development. In this review, we focus on the maintenance of epigenetic landscape during chromatin dynamics which requires the orchestration of histones and their chaperones. We discuss how epigenetic marks are re-established in the assembly of new chromatin after DNA replication and repair, highlighting the roles of CAF-1 in the process of changing chromatin state. The functions of CAF-1 provide a link between chromatin assembly and epigenetic restoration. PMID- 22314487 TI - Cell adhesion molecules in Drosophila synapse development and function. AB - Synapse is a highly specialized inter-cellular structure between neurons or between a neuron and its target cell that mediates cell-cell communications. Ample results indicate that synaptic adhesion molecules are critically important in modulating the complexity and specificity of the synapse. And disruption of adhesive properties of synapses may lead to neurodevelopmental or neurodegenerative diseases. In this review, we will use the Drosophila NMJ as a model system for glutamatergic synapses to discuss the structure and function of homophilic and heterophilic synaptic adhesion molecules with special focus on recent findings in neurexins and neuroligins in Drosophila. PMID- 22314488 TI - Phototransduction in Drosophila. AB - The Drosophila visual transduction is the fastest known G protein-coupled signaling cascade and has been served as a model for understanding the molecular mechanisms of other G protein-coupled signaling cascades. Numbers of components in visual transduction machinery have been identified. Based on the functional characterization of these genes, a model for Drosophila phototransduction has been outlined, including rhodopsin activation, phosphoinoside signaling, and the opening of TRP and TRPL channels. Recently, the characterization of mutants, showing slow termination, revealed the physiological significance and the mechanism of rapid termination of light response. PMID- 22314489 TI - Lipid metabolism and Drosophila sperm development. AB - Lipids are essential membrane structural components and important signal carriers. The major enzymatic metabolisms of various lipids (phospholipid, sphingolipid, cholesterol) are well studied. The developmental function of lipid metabolism has remained, for the most part, elusive. With the help of new techniques and model organisms, the important roles of lipid metabolism in development just start to emerge. Drosophila spermatogenesis is an ideal system for in vivo studies of cytokinesis and membrane remodeling during development. The metabolic regulators of many lipids, including phosphatidylinositol (PI) lipids, fatty acids and cholesterol, are reported to play critical roles in various steps during Drosophila spermatogenesis. In this mini-review, we summarized recent findings supporting a tight link between lipids metabolism and Drosophila sperm development. PMID- 22314490 TI - L-type calcium current in right ventricular outflow tract myocytes of rabbit heart. AB - The mechanism of idiopathic ventricular tachycardia originating from the right ventricular outflow tract (RVOT) is not clear. Many clinical reports have suggested a mechanism of triggered activity. However, there are few studies investigating this because of the technical difficulties associated with examining this theory. The L-type calcium current (I (Ca-L)), an important inward current of the action potential (AP), plays an important role in arrhythmogenesis. The aim of this study was to explore differences in the APs of right ventricular (RV) and RVOT cardiomyocytes, and differences in electrophysiological characteristics of the ICa-L in these myocytes. Rabbit RVOT and RV myocytes were isolated and their AP and I (Ca-L) were investigated using the patch-clamp technique. RVOT cardiomyocytes had a wider range of AP duration (APD) than RV cardiomyocytes, with some markedly prolonged APDs and markedly shortened APDs. The markedly shortened APDs in RVOT myocytes were abolished by treatment with 4-AP, an inhibitor of the transient outward potassium current, but the markedly prolonged APDs remained, with some myocytes with a long AP plateau not repolarizing to resting potential. In addition, early afterdepolarization (EAD) and second plateau responses were seen in RVOT myocytes but not in RV myocytes. RVOT myocytes had a higher current density for I (Ca-L) than RV myocytes (RVOT (13.16+/-0.87) pA pF(-1), RV (8.59+/-1.97) pA pF(-1); P<0.05). The I (Ca-L) and the prolonged APD were reduced, and the EAD and second plateau response disappeared, after treatment with nifedipine (10 MUmol L(-1)), which blocks the I (Ca-L). In conclusion, there was a wider range of APDs in RVOT myocytes than in RV myocytes, which is one of the basic factors involved in arrhythmogenesis. The higher current density for I (Ca-L) is one of the factors causing prolongation of the APD in RVOT myocytes. The combination of EAD with prolonged APD may be one of the mechanisms of RVOT-VT generation. PMID- 22314491 TI - AURKB and MAPK involvement in the regulation of the early stages of mouse zygote development. AB - Aurora kinases have become a hot topic for research as they have been found to play an important role in various stages of mitotic cell division and to participate in malignant conversions of tumors. The participation of Aurora kinases in the regulation of oocyte meiosis has been recently reported, but their participation in mammalian early embryonic development remained unclear. The object of our study was to establish the spatio-temporal expression pattern of Aurora kinase B (AURKB) in mouse zygotes during the first cleavage, to reveal its functions in the early development of mouse zygotes, and to define the involvement of AURKB in mitogen-activated protein kinase (MAPK) signaling. Our results showed that in mouse zygotes AURKB expression increased in G1 phase and peaked in M phase. AURKB protein distribution was found to be in association with nuclei and distributed throughout the cytoplasm in a cell cycle-dependent manner. Functional disruption of AURKB resulted in abnormal division phenotypes or mitotic impairments. U0126, a specific mitogen-activated protein kinase kinase (MEK) inhibitor, caused significantly altered morphologies of early embryos together with a decrease in protein expression and kinase activity of AURKB. Our results indicated that the activity of AURKB was required for regulating multiple stages of mitotic progression in the early development of mouse zygotes and was correlated with the activation of the MAPK pathway. PMID- 22314492 TI - A classification-based method to estimate event-related potentials from single trial EEG. AB - A novel method based on machine learning is developed to estimate event-related potentials from single trial electroencephalography. This paper builds a basic framework using classification and an optimization model based on this framework for estimating event-related potentials. Then the SingleTrialEM algorithm is derived by introducing a logistic regression model, which could be obtained by training before SingleTrialEM is used, to instantiate the optimization model. The simulation tests demonstrate that the proposed method is correct and solid. The advantage of this method is verified by the comparison between this method and the Woody filter in simulation tests. Also, the cognitive test results are consistent with the conclusions of cognitive science. PMID- 22314493 TI - Comparative analyses of leaf anatomy of dicotyledonous species in Tibetan and Inner Mongolian grasslands. AB - Knowledge of the leaf anatomy of grassland plants is crucial for understanding how these plants adapt to the environment. Tibetan alpine grasslands and Inner Mongolian temperate grasslands are two major grassland types in northern China. Tibetan alpine grasslands occur in high-altitude regions where the low temperatures limit plant growth. Inner Mongolian temperate grasslands are found in arid regions where moisture is the limiting factor. Few comparative studies concerning the leaf anatomy of grassland plants of the Tibetan Plateau and Inner Mongolian Plateau have been conducted. We examined leaf characteristics at 71 sites and among 65 species, across the alpine grasslands of the Tibetan Plateau and the temperate grasslands of the Inner Mongolian Plateau. We compared the leaf structures of plants with different life forms and taxonomies, and their adaptation to arid or cold environments. We explored relationships among leaf features and the effects of climatic factors (i.e., growing season temperature and precipitation) on leaf characteristics. Our results showed that (i) there were significant differences in leaf anatomy between Tibetan alpine and Inner Mongolian temperate grasslands. Except for mesophyll cell density, the values obtained for thickness of leaf tissue, surface area and volume of mesophyll cells were larger on the Tibetan Plateau than on the Inner Mongolian Plateau. (ii) Within the same family or genus, leaf anatomy showed significant differences between two regions, and trends were consistent with those of whole species. (iii) Leaf anatomy of woody and herbaceous plants also showed significant differences between the regions. Except for mesophyll cell density, the values obtained for the thickness of leaf tissue, and the surface area and volume of mesophyll cells were larger in herbaceous than in woody plants. (iv) Leaf anatomical traits changed accordingly. Total leaf thickness, thicknesses of lower and upper epidermal cells, and surface area and volume of mesophyll cells were positively correlated, while mesophyll cell density was negatively associated with those traits. (v) Growing season temperature had stronger effects on leaf anatomy than growing season precipitation. Although the communities in Tibetan and Inner Mongolian grasslands were similar in appearance, leaf anatomy differed; this was probably due to the combined effects of evolutionary adaptation of plants to environment and environmental stress induced by climatic factors. PMID- 22314494 TI - Selection of a DNA barcode for Nectriaceae from fungal whole-genomes. AB - A DNA barcode is a short segment of sequence that is able to distinguish species. A barcode must ideally contain enough variation to distinguish every individual species and be easily obtained. Fungi of Nectriaceae are economically important and show high species diversity. To establish a standard DNA barcode for this group of fungi, the genomes of Neurospora crassa and 30 other filamentous fungi were compared. The expect value was treated as a criterion to recognize homologous sequences. Four candidate markers, Hsp90, AAC, CDC48, and EF3, were tested for their feasibility as barcodes in the identification of 34 well established species belonging to 13 genera of Nectriaceae. Two hundred and fifteen sequences were analyzed. Intra- and inter-specific variations and the success rate of PCR amplification and sequencing were considered as important criteria for estimation of the candidate markers. Ultimately, the partial EF3 gene met the requirements for a good DNA barcode: No overlap was found between the intra- and inter-specific pairwise distances. The smallest inter-specific distance of EF3 gene was 3.19%, while the largest intra-specific distance was 1.79%. In addition, there was a high success rate in PCR and sequencing for this gene (96.3%). CDC48 showed sufficiently high sequence variation among species, but the PCR and sequencing success rate was 84% using a single pair of primers. Although the Hsp90 and AAC genes had higher PCR and sequencing success rates (96.3% and 97.5%, respectively), overlapping occurred between the intra- and inter-specific variations, which could lead to misidentification. Therefore, we propose the EF3 gene as a possible DNA barcode for the nectriaceous fungi. PMID- 22314495 TI - Functions of chromatin remodeling factors in heterochromatin formation and maintenance. AB - Heterochromatin is characteristically more compact than euchromatin in the eukaryotic genome. The establishment of heterochromatin is mediated by special histone modifications, recruitment and propagation of heterochromatin specific proteins, as well as formation of special primary and high order structures of chromatin. Chromatin remodeling factors are ATPases that can alter the conformation and/or positioning of nucleosomes along DNA in an ATP-dependent manner. There is increasing evidence implicating chromatin remodeling activities in heterochromatin in various organisms ranging from yeasts to humans. Chromatin remodeling factors play roles in the establishment, maintenance and epigenetic inheritance of heterochromatin, but the underlying molecular mechanisms have just begun to be investigated. PMID- 22314496 TI - A joint effect of new Western diet and retinoid X receptor alpha prostate specific knockout with development of high-grade prostatic intraepithelial neoplasia in mice--a preliminary study. AB - BACKGROUND: The "New Western-style Diet" (NWD) characterized by high in fat and low in fiber, vitamin D, calcium, and methyl donors--are considered as a risk factor for prostate cancer. Previous studies have shown that premalignant lesions of human prostate have decreased expression of the Retinoid X Receptor alpha (RXRalpha). This study was to determine the effect of diet in RXRalpha knockout mice in developing high-grade prostate intraepithelial neoplasia (mPIN). METHODS: Male mice (n = 54) with or without the RXRalpha prostate null mutation were fed either NWD or AIN-76A control diet for 10 months; prostates were harvested at 11 months of age and examined for prostate mPIN. RESULTS: mPIN was seen in 79% of RXRalpha prostate null mice fed NWD (n = 19), 30.8% RXRalpha prostate null mice fed AIN-76A (n = 13), 42.9% RXRalpha wild-type mice fed NWD (n = 14), and 12.5% RXRalpha wild-type mice fed AIN-76A (n = 8). Unconditional Logistic analysis showed a significant joint effect of NWD and RXRalpha status in developing mPIN 26.3 (95% CI: 2.5-280), but interaction was not significant owing to the small sample size 1.6 (0.09-27.7, P = 0.7441). CONCLUSION: This study provides preliminary data to support a joint RXRalpha-diet effect in prostate carcinogenesis. PMID- 22314497 TI - The interaction of iron pyrite with oxygen, nitrogen and nitrogen oxides: a first principles study. AB - Sulphide materials, in particular MoS(2), have recently received great attention from the surface science community due to their extraordinary catalytic properties. Interestingly, the chemical activity of iron pyrite (FeS(2)) (the most common sulphide mineral on Earth), and in particular its potential for catalytic applications, has not been investigated so thoroughly. In this study, we use density functional theory (DFT) to investigate the surface interactions of fundamental atmospheric components such as oxygen and nitrogen, and we have explored the adsorption and dissociation of nitrogen monoxide (NO) and nitrogen dioxide (NO(2)) on the FeS(2)(100) surface. Our results show that both those environmentally important NO(x) species chemisorb on the surface Fe sites, while the S sites are basically unreactive for all the molecular species considered in this study and even prevent NO(2) adsorption onto one of the non-equivalent Fe-Fe bridge sites of the (1 * 1)-FeS(2)(100) surface. From the calculated high barrier for NO and NO(2) direct dissociation on this surface, we can deduce that both nitrogen oxides species are adsorbed molecularly on pyrite surfaces. PMID- 22314498 TI - Hydrodynamic shearing of DNA in a polymeric microfluidic device. AB - With the advent of next-generation sequencing (NGS) systems and the associated high throughput they afford, the input to these machines requires manageable lengths of fragments (~1000 bp) produced from chromosomal DNAs. Therefore, it is critical to develop devices that can shear DNA in a controlled fashion. We report a polymer-based microfluidic device that establishes an efficient and inexpensive platform with performance comparable to a commercially available bench-top system. PMID- 22314499 TI - Epigenetic regulation of skin: focus on the Polycomb complex. AB - Chromatin regulators have recently emerged as key players in the control of tissue development and tumorigenesis. One specific chromatin regulator, the Polycomb complex, has been shown to regulate the identity of embryonic stem cells, but its role in controlling fates of multipotent progenitors in developing tissues is still largely unknown. Recent findings have revealed that this complex plays a critical role in control of skin stem cell renewal and differentiation. Moreover, the expression of Polycomb complex components is often aberrant in skin diseases, including skin cancers. This review will detail recent findings on Polycomb control of skin and highlight critical unknown questions. PMID- 22314500 TI - Palmitoylation by DHHC3 is critical for the function, expression, and stability of integrin alpha6beta4. AB - The laminin-binding integrin alpha6beta4 plays key roles in both normal epithelial and endothelial cells and during tumor cell progression, metastasis, and angiogenesis. Previous cysteine mutagenesis studies have suggested that palmitoylation of alpha6beta4 protein supports a few integrin-dependent functions and molecular associations. Here we took another approach and obtained strikingly different results. We used overexpression and RNAi knockdown in multiple cell types to identify protein acyl transferase DHHC3 as the enzyme responsible for integrin beta4 and alpha6 palmitoylation. Ablation of DHHC3 markedly diminished integrin-dependent cellular cable formation on Matrigel, integrin signaling through Src, and beta4 phosphorylation on key diagnostic amino acids (S1356 and 1424). However, unexpectedly, and in sharp contrast to prior alpha6beta4 mutagenesis results, knockdown of DHHC3 accelerated the degradation of alpha6beta4, likely due to an increase in endosomal exposure to cathepsin D. When proteolytic degradation was inhibited (by Pepstatin A), rescued alpha6beta4 accumulated intracellularly, but was unable to reach the cell surface. DHHC3 ablation effects were strongly selective for alpha6beta4. Cell-surface levels of ~10 other proteins (including alpha3beta1) were not diminished, and the appearance of hundreds of other palmitoylated proteins was not altered. Results obtained here demonstrate a new substrate for the DHHC3 enzyme and provide novel opportunities for modulating alpha6beta4 expression, distribution, and function. PMID- 22314501 TI - Molecular and functional heterogeneity of GABAergic synapses. AB - Knowledge of the functional organization of the GABAergic system, the main inhibitory neurotransmitter system, in the CNS has increased remarkably in recent years. In particular, substantial progress has been made in elucidating the molecular mechanisms underlying the formation and plasticity of GABAergic synapses. Evidence available ascribes a key role to the cytoplasmic protein gephyrin to form a postsynaptic scaffold anchoring GABA(A) receptors along with other transmembrane proteins and signaling molecules in the postsynaptic density. However, the mechanisms of gephyrin scaffolding remain elusive, notably because gephyrin can auto-aggregate spontaneously and lacks PDZ protein interaction domains found in a majority of scaffolding proteins. In addition, the structural diversity of GABA(A) receptors, which are pentameric channels encoded by a large family of subunits, has been largely overlooked in these studies. Finally, the role of the dystrophin-glycoprotein complex, present in a subset of GABAergic synapses in cortical structures, remains ill-defined. In this review, we discuss recent results derived mainly from the analysis of mutant mice lacking a specific GABA(A) receptor subtype or a core protein of the GABAergic postsynaptic density (neuroligin-2, collybistin), highlighting the molecular diversity of GABAergic synapses and its relevance for brain plasticity and function. In addition, we discuss the contribution of the dystrophin-glycoprotein complex to the molecular and functional heterogeneity of GABAergic synapses. PMID- 22314502 TI - Anti-inflammatory effect of proteoglycan and progesterone on human uterine cervical fibroblasts. AB - AIMS: The aim of this study was to compare the anti-inflammatory effect of proteoglycan (PG) with that of progesterone (P) in the cultured fibroblasts from human uterine cervix. MAIN METHODS: After obtaining informed consent, the cervix was collected from normal women undergoing total hysterectomy. The cervix was cultured until fibroblasts proliferated and had grown to confluence, then, the fibroblasts were stimulated by lipopolysaccharide (LPS) with or without PG, P and a combination of both; they were cultured for 24-48 h. The anti-inflammatory effects of PG and P were evaluated by the suppression of IL-6 or IL-8 secretion. The expression of the IL-6 or IL-8 gene and the expression of their protein were determined by real-time PCR, and ELISA, respectively. Activation of Toll-like receptor (TLR) 4 was evaluated by Western blotting. KEY FINDINGS: LPS markedly enhanced gene and protein expression of IL-6 and IL-8 in human uterine cervical fibroblasts. The up-regulation of the IL-6 or IL-8 gene and protein expression by LPS was significantly suppressed with PG, P and a combination of both. Western blotting revealed that combination of PG and P showed more potent inhibition on LPS-stimulated TLR4 induction than that seen by each. SIGNIFICANCE: This study showed that both PG and P have an inhibitory effect on LPS-induced inflammation. This anti-inflammatory effect of PG and P was augmented by co-administration of both, suggesting for the first time that PG has an anti-inflammatory effect on human uterine cervical fibroblasts. PMID- 22314503 TI - Synthesis of methoxybenzoflavones and assignments of their NMR data. AB - A phytotoxic root exudate from Acroptilon repens was identified as 7,8 benzoflavone, an inhibitor of cytochrome P450 1A2 and activator of cytochrome P450 3A4. The synthetic 5,6-benzoflavone also is a potent phytotoxin. Six 7,8 benzoflavones and eight 5,6-benzoflavones were synthesized in this study. The NMR data for a few of these compounds have been previously reported; however, the NMR data for most of them have not been reported. For reference purposes, the complete NMR data for the 14 benzoflavones are described. PMID- 22314504 TI - Deposition of chemically modified alpha-Al2O3 particles for high performance ZIF 8 membrane on a macroporous tube. AB - Through deposition of APTES-functionalized Al2O3 particles onto a coarse macroporous support, a new strategy to reduce the pore size and simutaneously promote a high density of heterogeneous nucleation sites was developed, and a continuous and thin ZIF-8 membrane exhibiting remarkably high H2 permeance of 5.73 * 10(-5) mol m(-2) s(-1) Pa(-1) and H2/N2 ideal selectivity of 15.4 was achieved. PMID- 22314505 TI - Quality and quantity: mucosal CD4+ T cells and HIV susceptibility. AB - PURPOSE OF REVIEW: The HIV sexual transmission probability measured in the context of discordant couples appears too low to fuel the HIV pandemic, but these rates are substantially amplified by specific co-factors. The most consistent predictors of transmission are the HIV levels in the blood and genital tract of an infected individual, each of which increases the transmission probability in a dose-dependent manner. In an analogous fashion, we propose that both the quantity and quality of HIV-susceptible target cells in the exposed genital or rectal mucosa may be key predictors of HIV susceptibility. RECENT FINDINGS: The absolute number of mucosal CD4+ T cells is increased in several situations that are associated with amplified HIV transmission, particularly during genital infections. In addition, qualitative mucosal T-cell parameters such as immune activation and the expression of the HIV binding molecules CCR5 and/or alpha4beta7 are important determinants of gp120 binding and productive HIV infection. In particular, the Th17 and Th22 cell subsets are enhanced within mucosal compartments and appear to be highly HIV-susceptible. SUMMARY: Blockade of specific HIV target cell subsets at the site of exposure, if done in a safe and effective manner, represents an opportunity for new HIV prevention tools. PMID- 22314506 TI - Testing for acute HIV infection: implications for treatment as prevention. AB - PURPOSE OF REVIEW: The aim of this study is to give an overview of the recent literature related to HIV testing with an emphasis on detecting acute HIV infection. Testing technology as well as implications for treatment as prevention will be discussed. RECENT FINDINGS: HIV testing technology continues to evolve. Advances include updated immunologic formats that detect both HIV antibody and antigen (4th generation assays), new nucleic acid amplification tests, and continued development of rapid assays that can be used in either clinical or nonclinical settings. Because of these advances there are proposed changes for HIV diagnostic algorithms to encourage detection of acute infection. These technologic advances have implications for HIV prevention as testing is a cornerstone for all HIV prevention strategies. There is considerable new research indicating that treatment may be an important aspect of HIV prevention. Data also suggest that detection of acute infection will be important for the success of these prevention strategies. SUMMARY: Continued improvements in technology and testing practice are vital for the success of HIV prevention. Detection of acute or early HIV infection will likely play a key role in the success of treatment as prevention, as well as play an important role in ongoing behavioral prevention strategies. PMID- 22314507 TI - [Sudden death in athletes: is screening necessary?]. PMID- 22314508 TI - [Icy streets; prevention and public responsibility]. PMID- 22314509 TI - [Screening for risk factors of sudden cardiac death in young athletes]. AB - OBJECTIVE: Sudden cardiac death in young athletes is relatively uncommon and is usually caused by occult underlying cardiovascular disease. Studies have indicated that preparticipation screening may reduce the incidence of sudden death. Our aim was to study the feasibility of standardized preparticipation screening in young competitive Icelandic athletes. The prevalence of risk factors was studied in order to evaluate how often further examination is indicated and to assess possible costs. MATERIAL AND METHODS: A total of 105 randomly selected competitive athletes (70 men, 35 women) between the age 18-35 received standard screening with medical history, cardiac examination and 12 lead ECG. RESULTS: The most frequent complaints revealed by medical history were allergy, excema, asthma, dyspnea on exercise, chest pain on exercise, palpitations on exercise, dizziness and fainting on exercise. Physical examination was abnormal in 20 (19%). 12 lead ECG was distinctly abnormal in 22 (21%) and mildly abnormal in 23 (22%). Transthoracal echocardiography (TTE) was performed on 19 (18%). Of those, TTE was normal in six athletes (32%) and mildly abnormal in 13 (68%), none had abnormal findings indicating structural heart disease. CONCLUSION: Symptoms associated with cardiac disease are frequently described among young athletes. Abnormal ECG was commonly found. Further examination with echocardiography may be indicated in one of every four athletes screened. PMID- 22314510 TI - [Kawasaki disease in Iceland 1996-2005, epidemiology and complications]. AB - OBJECTIVE: To analyze the epidemiology of Kawasaki disease in Icelandic children and its complications. METHODS: A retrospective analysis of all cases of Kawasaki disease and atypical Kawasaki disease in children in Iceland from 1996-2005. Chart records were reviewed and children diagnosed at Landspitali - University Hospital invited for a Follow up study with emphasis on heart complications. RESULTS: Thirty children were diagnosed with Kawasaki disease, annual incidence was 10.7/100.000 children <5 years of age. The boy:girl ratio was 2.3:1. All 30 children were treated with IVIG, without any major adverse events related to the treatment. The median time from the initial symptoms to treatment was six days (range 3-31 days). There was no mortality. Two children developed coronary aneurysms and three coronary ectasia. Follow up echocardiography was preformed in 23 of the children four to twelve years after Kawasaki disease. Two of the children still had coronary ectasia, and six (26%) had mitral regurgitation. CONCLUSIONS: The incidence of Kawasaki disease in Iceland was comparable to an earlier Icelandic study and reported incidence in the Nordic countries. Coronary involvement during the acute phase was mild, and all coronary aneurysm regressed. Serious cardiac complications were not seen. Children with Kawasaki disease in Iceland have favorable prognosis. Interestingly, mild mitral regurgitation and coronary ectasia were common at mid-term follow up. PMID- 22314511 TI - [Percutaneous endoscopic gastrostomy in Iceland over 10 year period: a retrospective study of indications, complications and ethical issues]. AB - OBJECTIVE: Percutaneous endoscopic gastrostomy (PEG) is the preferred method for long term enteral feeding. No nationwide study has reported on the experience and outcome of PEG procedure. The aim of this study was to describe the frequency, indications, complications, mortality and ethical issues related to PEG procedures in Iceland. MATERIAL AND METHODS: A retrospective study was performed on all adult patients who had PEG procedures in Iceland between 2000-2009. Medical charts from patients found were reviewed and data regarding demographics, indications, complications, mortality and ethically controversial cases was obtained. RESULTS: A total of 278 patients had PEG procedures during the 10 year study period. There were 163 men and 115 women with a median age of 70 years. The mean annual incidence of PEG procedures was 12.8/100.000. Sufficient medical data for evaluation was obtained from 263 patients. The most common indications were neurological disorders (61%) and malignancies (13%). Dementia accounted for only 0.8% of the indications. Total complication rate was 6.5% with 1.9% being major and 4.6% minor complications. Peritonitis was the most common (2.7%) complication followed by peristomal skin infection (1.9%). Operative mortality was 0.8% and 30 day mortality rate was 13%. In seven (2.7%) cases the PEG procedure was considered to be ethically and medically controversial. CONCLUSION: This is the first published nationwide study on the experience of PEG procedures. The complication and mortality rates in Iceland are among the lowest reported. The indications reported here are in agreement with national guidelines with the rate of PEG procedures in ethically controversial cases being very rare. PMID- 22314512 TI - [Accidents on Iceland's most dangerous roads]. AB - OBJECTIVE: The objective of this paper was to identify the most dangerous segments of the Icelandic road system in terms of the number of accidents pr km and the rate of accidents pr million km travelled. First to identify the segments where the number of accidents is highest and where the risk of the individual traveller is the greatest. Second to evaluate if the association between the number and the rate of accidents is positive or negative. Third to identify the road segments that are the most dangerous in the sense of many accidents and great risk to individual travellers. MATERIAL AND METHODS: Main roads outside urban centers were divided into 45 segments that were on average 78 km in length. Infrequently travelled roads and roads within urban centers were omitted. Information on the length of roads, traffic density and number of accidents was used to calculate the number of accidents per km and the rate of accidents per million km travelled. The correlation between the number and rate of accidents was calculated and the most dangerous road segments were identified by the average rank order on both dimensions. RESULTS: Most accidents pr km occurred on the main roads to and from the capital region, but also east towards Hvolsvollur, north towards Akureyri and in the Mideast region of the country. The rate of accidents pr million km travelled was highest in the northeast region, in northern Snaefellsnes and in the Westfjords. The most dangerous roads on both dimensions were in Mideast, northern Westfjords, in the north between Blonduos and Akureyri and in northern Snaefellsnes. CONCLUSION: Most accidents pr km occurred on roads with a low accident rate pr million km travelled. It is therefore possible to reduce accidents the most by increasing road safety where it is already the greatest but that would however increase inequalities in road safety. Policy development in transportation is therefore in part a question of priorities in healthcare. Individual equality in safety and health are not always fully compatible with economic concerns and the interests of the majority. PMID- 22314513 TI - Metal concentrations in the soils and native plants surrounding the old flotation tailings pond of the copper mining and smelting complex Bor (Serbia). AB - In this study concentrations of metals in the native plants and soils surrounding the old flotation tailings pond of the copper mine were determined. It has been established that the soil is heavily contaminated with copper, iron and arsenic, the mean concentrations being 1585.6, 29,462.5 and 171.7 mg kg(-1) respectively. All the plants, except manganese, accumulated metallic elements in concentrations which were either in the range of critical and phytotoxic values (Pb and As) or higher (Zn), and even much higher (Cu and Fe) than these values. Otherwise, the accumulation of Mn, Pb and As was considerably lower than that of Cu, Fe and Zn. In most plants the accumulation of target metals was highest in the root. Several plant species showed high bioaccumulation and translocation factor values, which classify them into species for potential use in phytoextraction. The BCF and TF values determined in Prunus persica were 1.20 and 3.95 for Cu, 1.5 and 6.0 for Zn and 1.96 and 5.44 for Pb. In Saponaria officinalis these values were 2.53 and 1.27 for Zn, and in Juglans regia L. they were 8.76 and 17.75 for Zn. The translocation factor in most plants, for most metals, was higher than one, whereas the highest value was determined in Populus nigra for Zn, amounting to 17.8. Among several tolerant species, the most suitable ones for phytostabilization proved to be Robinia pseudoacacia L. for Zn and Verbascum phlomoides L., Saponaria officinalis and Centaurea jacea L. for Mn, Pb and As. PMID- 22314514 TI - A dodecapeptide (YQVTQSKVMSHR) exhibits antibacterial effect and induces cell aggregation in Escherichia coli. AB - Antimicrobial peptides play an important role in the innate immune response and host defense mechanism. In the present study, we employed phage display technique to screen for inhibitors which may block the phosphoenolpyruvatedependent phosphotransferase system (PTS) pathway and hence retard cell growth. The recombinant histidine-containing phosphocarrier HPr protein was prepared as the target to screen for the tight binders from the phage-displayed random peptide library Ph.D.-12. The biopanning processes were performed and the binding capabilities of the selected phage were further estimated by enzyme-linked immunosorbent assay (ELISA). The single-stranded DNAs of the 20 selected phages were isolated, sequenced, and five corresponding peptides were synthesized. Only one of the five peptides, AP1 (YQVTQSK VMSHR) was found to inhibit the growth of Escherichia coli cells efficiently (IC50~50 MUM). Molecular modeling reveals that AP1 may block the EI-HPr interaction and phosphotransfer. Interestingly, AP1 was also found to induce cell aggregation in a concentration-dependent manner. Since glycogen accumulation has been attributed to biofilm formation, the effects of AP1 on the intracellular glycogen levels were measured. The results strongly indicate that the cell aggregation may be caused by the binding of peptide AP1 with HPr to block the interaction of dephosphorylated HPr with glycogen phosphorylase (GP). Because glycogen phosphorylase activity can be activated by HPr-GP interaction, the binding of AP1 to HPr would cause a decreasing rate of glycogen breakdown in M9 medium and accumulation of glycogen, which may lead to eventual cell aggregation. To the best of our knowledge, this is the first study to demonstrate that an inhibitor bound to a dephosphorylated HPr can decouple its regulatory function and induce cell aggregation. PMID- 22314515 TI - Mannanases: microbial sources, production, properties and potential biotechnological applications. AB - Mannans are the major constituents of the hemicellulose fraction in softwoods and show widespread distribution in plant tissues. The major mannan-degrading enzymes are beta-mannanases, beta-mannosidases and beta-glucosidases. In addition to these, other enzymes such as alpha-galactosidases and acetyl mannan esterases, are required to remove the side chain substituents. The mannanases are known to be produced by a variety of bacteria, fungi, actinomycetes, plants and animals. Microbial mannanases are mainly extracellular and can act in wide range of pH and temperature because of which they have found applications in pulp and paper, pharmaceutical, food, feed, oil and textile industries. This review summarizes the studies on mannanases reported in recent years in terms of important microbial sources, production conditions, enzyme properties, heterologous expression and potential industrial applications. PMID- 22314516 TI - High-yield enzymatic bioconversion of hydroquinone to alpha-arbutin, a powerful skin lightening agent, by amylosucrase. AB - alpha-Arbutin (alpha-Ab) is a powerful skin whitening agent that blocks epidermal melanin biosynthesis by inhibiting the enzymatic oxidation of tyrosine and L-3,4 dihydroxyphenylalanine (L-DOPA). alpha-Ab was effectively synthesized from hydroquinone (HQ) by enzymatic biotransformation using amylosucrase (ASase). The ASase gene from Deinococcus geothermalis (DGAS) was expressed and efficiently purified from Escherichia coli using a constitutive expression system. The expressed DGAS was functional and performed a glycosyltransferase reaction using sucrose as a donor and HQ as an acceptor. The presence of a single HQ bioconversion product was confirmed by thin-layer chromatography (TLC) and high performance liquid chromatography (HPLC). The HQ bioconversion product was isolated by silica gel open column chromatography and its chemical structure determined by 1H and 13C nuclear magnetic resonance (NMR). The product was determined to be hydroquinone-O-alpha-D-glucopyranoside with a glucose molecule linked to HQ through an alpha-glycosidic bond. However, the production yield of the transfer reaction was significantly low (1.3%) due to the instability of HQ in the reaction mixture. The instability of HQ was considerably improved by antioxidant agents, particularly ascorbic acid, implying that HQ is labile to oxidation. A maximum yield of HQ transfer product of 90% was obtained at a 10:1 molar ratio of donor (sucrose) and acceptor (HQ) molecules in the presence of 0.2 mM ascorbic acid. PMID- 22314517 TI - Elevated poly(3-hydroxybutyrate) synthesis in mutants of Ralstonia eutropha H16 defective in lipopolysaccharide biosynthesis. AB - Several independent transposon Tn5-induced mutants of Ralstonia eutropha H16 exhibited a poly(3-hydroxybutyric acid) (PHB) elevated phenotype and accumulated substantial amounts of PHB already in the exponential growth phase. The insertion loci of Tn5 in these six mutants were mapped in the genes hldA (twice), hldC (twice), rfaF2, and rfaF3, which are all involved in the synthesis of lipopolysaccharides (LPS), an important component of the outer membrane (OM) of Gram-negative bacteria. The generated defined deletion mutant DeltahldA confirmed the PHB elevated phenotype. According to the literature,such a truncated LPS may cause an increased permeability of the OM; thereby, the mutations may lead to a facilitated uptake of carbon source from the medium as exemplarily shown for gluconate and succinate. Thus, the ratio of carbon to nitrogen in the cell is increased. Proteome analyses revealed reinforcement of the Entner-Doudoroff pathway and of subsequent reactions that finally may lead to higher concentrations of acetyl-CoA in the cells. Due to the impaired synthesis of complete LPS, intermediates of LPS biosynthesis might be recycled by reactions yielding higher levels of NADPH and acetyl-CoA. Since the latter are precursors for synthesis of PHB, this could explain the elevated synthesis and accumulation of this polymer in case of the LPS mutants. PMID- 22314518 TI - A multi-electrode continuous flow microbial fuel cell with separator electrode assembly design. AB - Scaling up microbial fuel cells (MFCs) requires the development of compact reactors with multiple electrodes. A scalable single chamber MFC (130 mL), with multiple graphite fiber brush anodes and a single air-cathode cathode chamber (27 m2/m3), was designed with a separator electrode assembly (SEA) to minimize electrode spacing. The maximum voltage produced in fed-batch operation was 0.65 V (1,000 Omega) with a textile separator, compared to only 0.18 V with a glass fiber separator due to short-circuiting by anode bristles through this separator with the cathode. The maximum power density was 975 mW/m2, with an overall chemical oxygen demand (COD) removal of >90% and a maximum coulombic efficiency (CE) of 53% (50 Omega resistor). When the reactor was switched to continuous flow operation at a hydraulic retention time (HRT) of 8 h, the cell voltage was 0.21 +/- 0.04 V, with a very high CE = 85%. Voltage was reduced to 0.13 +/- 0.03 V at a longer HRT = 16 h due to a lower average COD concentration, and the CE (80%) decreased slightly with increased oxygen intrusion into the reactor per amount of COD removed. Total internal resistance was 33 Omega, with a solution resistance of 2 Omega. These results show that the SEA type MFC can produce stable power and a high CE, making it useful for future continuous flow treatment using actual wastewaters. PMID- 22314519 TI - Clinical outcomes of spinal surgery in patients treated with hemodialysis. AB - STUDY DESIGN: Retrospective study. OBJECTIVE: The purpose of this study is to review clinical outcomes, including survival rate, and to discuss the potential benefit of surgical treatments for spinal disorders in patients treated with long term hemodialysis (HD). SUMMARY OF BACKGROUND DATA: Long-term HD is known to possibly cause destructive spondyloarthropathy (DSA) with spinal canal stenosis. There have been few reports, however, regarding clinical outcomes and patient survival rates after spinal surgeries in this population. METHODS: We retrospectively reviewed 33 chronic HD patients who underwent 21 cervical and 13 lumbar spinal surgeries. According to the radiologic findings, we divided them into the non-DSA and the DSA groups. In general, only decompression was performed for the non-DSA patients, whereas spinal fusion was added for the DSA patients. We analyzed the following data, respectively: male-female ratio, age, operative time, estimated blood loss, duration of HD, follow-up duration, preoperative and postoperative Japanese Orthopaedic Association score, improvement ratio of the Japanese Orthopaedic Association score, amyloid deposition characteristics, and survival rate. RESULTS: All patients improved neurologically and functionally after surgery. There were significant differences in the operative time between the DSA and the non-DSA groups in patients with cervical spinal lesions, whereas in patients with lumbar spinal lesions, there were significant differences in sex, operative time, and estimated blood loss. Amyloid deposition was found signficantly more commonly in DSA than in non-DSA patients and was associated with a longer duration of HD. Nine patients died within 49 months of the surgery because of HD-related complications, but there was no surgery-related morbidity. Kaplan-Meier analysis showed a trend toward decreased survival rate in non-DSA patients more than 40 months after the index surgery. CONCLUSIONS: Even in patients treated with long-term HD, spinal surgeries reliably obtain neurological and functional improvement if surgeons judge the preoperative inclusion criteria correctly. However, if surgeries are necessary for these patients, surgeons should consider the patients' comorbidity-related survival rate after the spinal surgeries. PMID- 22314520 TI - Comparison of the pedicle screws placement between electronic conductivity device and normal pedicle finder in posterior surgery of scoliosis. AB - STUDY DESIGN: Prospective randomized clinical trial. OBJECTIVE: To compare the accuracy and time using of pedicle screw placement between electronic conductivity device (ECD) and normal pedicle finder (NPF) in posterior surgery of scoliosis, through a randomized clinical trial. SUMMARY OF BACKGROUND DATA: Pedicle screw insertion for scoliosis correction can be associated with increased pedicle perforations. The malposition rates using various techniques in different region of the spine have been reported to occur with a frequency of 3.3%-43%. An ECD has been reported in spine surgeries, but its accuracy and surgical time comparing with NPF in the presence of scoliosis has not been reported. METHODS: The 42 patients of adolescent idiopathic scoliosis with average major Cobb angle of 55.3+/-7 degrees (range, 45-78 degrees), who received posterior correction surgeries using pedicle screws system only were divided into 2 groups by random: group NPF (22 patients); and group ECD (20 patients). NPF group had 332 screws and ECD group had 362 screws. The 2 groups were compared for accuracy of screw placement, time for screw insertion, and the number of times the C-arm had to be brought into the field. RESULTS: There were 47 (14.2%) pedicle perforation in the NPF group as compared with only 15 (4.1%) in the ECD group (P<0.001). Although in different region of the spine, screw accuracy showed discrepant statistical result, with upper (T1-T3), middle (T4-T7), and lower thoracic (T8-T10) comparison showing significant statistical difference (P=0.010, 0.001, and 0.041, respectively) and thoracolumbar (T11-L2) and lower lumbar (L3-L5) comparison showing no significant statistical difference (P=0.278 and 0.292, respectively). Average screw insertion time in the NPF group was 241+/-61 seconds compared with 204+/-33 seconds in the ECD group (P=0.009). The C-arm had to be moved into the operation field on an average of 1.59+/-0.67 times in the NPF group compared with 1.20+/-0.52 in the ECD group (P=0.040). CONCLUSIONS: ECD increases pedicle screw accuracy, especially in T1-T10, and reduces insertion time and radiation in posterior adolescent idiopathic scoliosis. PMID- 22314521 TI - Early endpoints for acute bacterial skin and skin structure infections. PMID- 22314522 TI - Induction of oxidative stress in Trypanosoma brucei by the antitrypanosomal dihydroquinoline OSU-40. AB - Dihydroquinoline derivative OSU-40 (1-benzyl-1,2-dihydro-2,2,4-trimethylquinolin 6-yl acetate) is selectively potent against Trypanosma brucei rhodesiense in vitro (50% inhibitory concentration [IC(50)], 14 nM; selectivity index, 1,700) and has been proposed to cause the formation of reactive oxygen species (ROS) in African trypanosomes (J. Fotie et al., J. Med. Chem. 53:966-982, 2010). In the present study, we sought to provide further support for the hypothesis that OSU 40 kills trypanosomes through oxidative stress. Inducible RNA interference (RNAi) was applied to downregulate key enzymes in parasite antioxidant defense, including T. brucei trypanothione synthetase (TbTryS) and superoxide dismutase B (TbSODB). Both TbTryS RNAi-induced and TbSODB RNAi-induced cells showed impaired growth and increased sensitivity toward OSU-40 by 2.4-fold and 3.4-fold, respectively. Decreased expression of key parasite antioxidant enzymes was thus associated with increased sensitivity to OSU-40, consistent with the hypothesis that OSU-40 acts through oxidative stress. Finally, the dose-dependent formation of free radicals was observed after incubation of T. brucei with OSU-40 utilizing electron spin resonance (ESR) spectroscopy. These data support the notion that the mode of antitrypanosomal action for this class of compounds is to induce oxidative stress. PMID- 22314523 TI - Exploiting the anti-HIV-1 activity of acyclovir: suppression of primary and drug resistant HIV isolates and potentiation of the activity by ribavirin. AB - Multiple clinical trials have demonstrated that herpes simplex virus 2 (HSV-2) suppressive therapy using acyclovir (ACV) or valacyclovir in HIV-1/HSV-2-infected persons increased the patient's survival and decreased the HIV-1 load. It has been shown that the incorporation of ACV-monophosphate into the nascent DNA chain instead of dGMP results in the termination of viral DNA elongation and directly inhibits laboratory strains of HIV-1. We evaluated here the anti-HIV activity of ACV against primary HIV-1 isolates of different clades and coreceptor specificity and against viral isolates resistant to currently used drugs, including zidovudine, lamivudine, nevirapine, a combination of nucleoside reverse transcriptase inhibitors (NRTIs), a fusion inhibitor, and two protease inhibitors. We found that, at clinically relevant concentrations, ACV inhibits the replication of these isolates in human tissues infected ex vivo. Moreover, addition of ribavirin, an antiviral capable of depleting the pool of intracellular dGTP, potentiated the ACV-mediated HIV-1 suppression. These data warrant further clinical investigations of the benefits of using inexpensive and safe ACV alone or in combination with other drugs against HIV-1, especially to complement or delay highly active antiretroviral therapy (HAART) initiation in low-resource settings. PMID- 22314524 TI - CANVAS 1 and 2: analysis of clinical response at day 3 in two phase 3 trials of ceftaroline fosamil versus vancomycin plus aztreonam in treatment of acute bacterial skin and skin structure infections. AB - Scientific and regulatory interest in assessing clinical endpoints after 48 to 72 h of treatment for acute bacterial skin and skin structure infections (ABSSSI) has increased. Historical, pre-antibiotic-era data suggest that a treatment effect relative to untreated controls can be discerned in this time interval. Ceftaroline fosamil, a broad-spectrum bactericidal cephalosporin with activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA), and Gram-negative organisms was efficacious in two phase 3 trials of complicated skin infections (CANVAS 1 and 2) using clinical cure rates at the test-of-cure visit. To assess an early clinical response in the CANVAS trials, a retrospective analysis using a day 3 clinical endpoint was conducted. Adults with ABSSSI received intravenous ceftaroline fosamil at 600 mg every 12 h (q12h) or vancomycin at 1 g plus aztreonam at 1 g (V/A) q12h for 5 to 14 days. Clinical response at day 3, defined as cessation of infection spread and absence of fever, was analyzed in patients with a lesion size of >= 75 cm(2) and either deep and/or extensive cellulitis, major abscess, or an infected wound. Day 3 integrated CANVAS clinical response rates were 74.0% (296/400) for ceftaroline and 66.2% (263/397) for V/A (difference, 7.8%; 95% confidence interval [CI], 1.3% to 14.0%). In the individual studies, absolute treatment differences of 9.4% (CANVAS 1) and 5.9% (CANVAS 2) favoring ceftaroline were observed. For ABSSSI due to MRSA, response rates were 81.7% and 77.4% in the ceftaroline and V/A groups, respectively. In this retrospective analysis, ceftaroline fosamil monotherapy had a numerically higher clinical response than V/A at day 3 in the treatment of ABSSSI. PMID- 22314525 TI - Product quality of parenteral vancomycin products in the United States. AB - In response to concerns raised about the quality of parenteral vancomycin products, the U.S. Food and Drug Administration (FDA) is investigating the product quality of all FDA-approved parenteral vancomycin products available in the United States. Product quality was evaluated independently at two FDA Office of Testing and Research (FDA-OTR) sites. In the next phase of the investigation, being done in collaboration with the National Institute of Allergy and Infectious Diseases, the in vivo activity of these products will be evaluated in an appropriate animal model. This paper summarizes results of the FDA investigation completed thus far. One site used a validated ultrahigh-pressure liquid chromatography method (OTR-UPLC), and the second site used the high-performance liquid chromatography (HPLC) method for related substances provided in the British Pharmacopeia (BP) monograph for vancomycin intravenous infusion. Similar results were obtained by the two FDA-OTR laboratories using two different analytical methods. The products tested had 90 to 95% vancomycin B (active component of vancomycin) by the BP-HPLC method and 89 to 94% vancomycin by OTR UPLC methods. Total impurities were 5 to 10% by BP-HPLC and 6 to 11% by OTR-UPLC methods. No single impurity was >2.0%, and the CDP-1 level was <= 2.0% across all products. Some variability in impurity profiles of the various products was observed. No adverse product quality issues were identified with the six U.S. vancomycin parenteral products. The quality parameters of all parenteral vancomycin products tested surpassed the United States Pharmacopeia acceptance criteria. Additional testing will characterize in vivo performance characteristics of these products. PMID- 22314526 TI - Integrating conjugative elements as vectors of antibiotic, mercury, and quaternary ammonium compound resistance in marine aquaculture environments. AB - The presence of SXT/R391-related integrating conjugative elements (ICEs) in bacterial strains isolated from fish obtained from marine aquaculture environments in 2001 to 2010 in the northwestern Iberian Peninsula was studied. ICEs were detected in 12 strains taxonomically related to Vibrio scophthalmi (3 strains), Vibrio splendidus (5 strains), Vibrio alginolyticus (1 strain), Shewanella haliotis (1 strain), and Enterovibrio nigricans (2 strains), broadening the known host range able to harbor SXT/R391-like ICEs. Variable DNA regions, which confer element-specific properties to ICEs of this family, were characterized. One of the ICEs encoded antibiotic resistance functions in variable region III, consisting of a tetracycline resistance locus. Interestingly, hot spot 4 included genes providing resistance to rifampin (ICEVspPor2 and ICEValPor1) and quaternary ammonium compounds (QACs) (ICEEniSpa1), and variable region IV included a mercury resistance operon (ICEVspSpa1 and ICEEniSpa1). The S exclusion group was more represented than the R exclusion group, accounting for two-thirds of the total ICEs. Mating experiments allowed ICE mobilization to Escherichia coli strains, showing the corresponding transconjugants' rifampin, mercury, and QAC resistance. These results show the first evidence of ICEs providing rifampin and QAC resistances, suggesting that these mobile genetic elements contribute to the dissemination of antimicrobial, heavy metal, and QAC resistance determinants in aquaculture environments. PMID- 22314527 TI - Efflux pumps of Mycobacterium tuberculosis play a significant role in antituberculosis activity of potential drug candidates. AB - Active efflux of drugs mediated by efflux pumps that confer drug resistance is one of the mechanisms developed by bacteria to counter the adverse effects of antibiotics and chemicals. To understand these efflux mechanisms in Mycobacterium tuberculosis, we generated knockout (KO) mutants of four efflux pumps of the pathogen belonging to different classes. We measured the MICs and kill values of two different compound classes on the wild type (WT) and the efflux pump (EP) KO mutants in the presence and absence of the efflux inhibitors verapamil and l phenylalanyl-l-arginyl-beta-naphthylamide (PAbetaN). Among the pumps studied, the efflux pumps belonging to the ABC (ATP-binding cassette) class, encoded by Rv1218c, and the SMR (small multidrug resistance) class, encoded by Rv3065, appear to play important roles in mediating the efflux of different chemical classes and antibiotics. Efflux pumps encoded by Rv0849 and Rv1258c also mediate the efflux of these compounds, but to a lesser extent. Increased killing is observed in WT M. tuberculosis cells by these compounds in the presence of either verapamil or PAbetaN. The efflux pump KO mutants were more susceptible to these compounds in the presence of efflux inhibitors. We have shown that these four efflux pumps of M. tuberculosis play a vital role in mediating efflux of different chemical scaffolds. Inhibitors of one or several of these efflux pumps could have a significant impact in the treatment of tuberculosis. The identification and characterization of Rv0849, a new efflux pump belonging to the MFS (major facilitator superfamily) class, are reported. PMID- 22314528 TI - MK-4815, a potential new oral agent for treatment of malaria. AB - Malaria continues to have a significant impact on the health of the developing world. Efforts to combat this disease now focus on combination therapy in order to stem the emergence of resistant parasites. Continued efforts are needed to discover and develop new agents for use in combination antimalarial regimens. MK 4815 is a small molecule with antimalarial activity that was identified from a large pharmaceutical compound collection using a semiautomated version of a well established in vitro assay for the erythrocytic stages of Plasmodium falciparum. In vitro studies indicate that the compound selectively accumulates in infected red blood cells and is most effective against the metabolically active late trophozoite/early schizont stages. A variety of drug-resistant field isolates of P. falciparum were found to be as sensitive to MK-4815 as the wild-type lines. MK 4815 is orally active in a P. berghei mouse model of acute malaria. In this model, where untreated animals succumb to infection 10 to 12 days postinfection, MK-4815 was completely curative when given as a single dose of 50 mg/kg, 2 doses of 25 mg/kg, or 4.5 doses of 12.5 mg/kg. In pharmacokinetic studies with mice and rhesus monkeys, MK-4815 demonstrated oral bioavailability and low clearance. In addition, MK-4815 is inexpensive to synthesize, an important characteristic for providing affordable antimalaria therapy to the developing world. The attractive biological and pharmaceutical profile of MK-4815 demonstrates its potential for use in combination with other agents in the fight against malaria. PMID- 22314529 TI - blaNDM-1 is a chimera likely constructed in Acinetobacter baumannii. AB - Alignment of DNA sequences found upstream of aphA6 and all bla(NDM-1) genes displays 100% identity. This identity continues 19 bp into the bla(NDM-1) gene such that the first 6 amino acids of aphA6 and bla(NDM-1) are the same. Furthermore, the percent GC content (GC%) of aphA6 is considerably lower than that of bla(NDM-1) and the GC% within the bla(NDM-1) structural gene changes dramatically after the first 19 bp. This is unequivocal evidence that bla(NDM-1) is a chimera. PMID- 22314530 TI - Microbiological aetiology, epidemiology, and clinical profile of prosthetic joint infections: are current antibiotic prophylaxis guidelines effective? AB - Prosthetic joint infections remain a major complication of arthroplasty. At present, local and international guidelines recommend cefazolin as a surgical antibiotic prophylaxis at the time of arthroplasty. This retrospective cohort study conducted across 10 hospitals over a 3-year period (January 2006 to December 2008) investigated the epidemiology and microbiological etiology of prosthetic joint infections. There were 163 cases of prosthetic joint infection identified. From a review of the microbiological culture results, methicillin resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci were isolated in 45% of infections. In addition, polymicrobial infections, particularly those involving Gram-negative bacilli and enterococcal species, were common (36%). The majority (88%) of patients received cefazolin as an antibiotic prophylaxis at the time of arthroplasty. In 63% of patients in this cohort, the microorganisms subsequently obtained were not susceptible to the antibiotic prophylaxis administered. The results of this study highlight the importance of ongoing reviews of the local ecology of prosthetic joint infection, demonstrating that the spectrum of pathogens involved is broad. The results should inform empirical antibiotic therapy. This report also provokes discussion about infection control strategies, including changing surgical antibiotic prophylaxis to a combination of glycopeptide and cefazolin, to reduce the incidence of infections due to methicillin-resistant staphylococci. PMID- 22314531 TI - Clonal dissemination of linezolid-resistant Staphylococcus haemolyticus exhibiting the G2576T mutation in the 23S rRNA gene in a tertiary care hospital in Brazil. PMID- 22314532 TI - Safety and efficacy of GSK2248761, a next-generation nonnucleoside reverse transcriptase inhibitor, in treatment-naive HIV-1-infected subjects. AB - GSK2248761 is a novel, once-daily (QD), next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) with activity against efavirenz-resistant strains. Two phase I/IIa, double-blind, randomized, placebo-controlled studies investigated the antiviral activity, safety, and pharmacokinetics (PK) of several doses of GSK2248761 monotherapy in treatment-naive HIV-infected subjects. In the initial study, 10 subjects (8 active and 2 placebo) per dose received sequentially descending GSK2248761 monotherapy regimens of 800, 400, 200, and 100 mg QD for 7 days. Because a dose-response relationship was not identified, a second study examined a lower, 30-mg QD dose in 8 subjects (6 active and 2 placebo). Adverse events, viral load (VL), PK, and reverse transcriptase mutations were assessed and combined for analysis. Treatment with GSK2248761 for 7 days was well tolerated with no serious adverse events or discontinuations. The mean VL reductions from baseline on day 8 were 0.97, 1.87, 1.84, 1.81, and 1.78 log(10) copies/ml for GSK2248761 doses of 30, 100, 200, 400, and 800 mg QD, respectively. GSK2248761 PK (maximum drug concentration in serum [C(max)], area under the plasma concentration-time curve from 0 h to the end of the dosing interval [AUC(0-tau)], and concentration at the end of the dosing interval [C(tau)]) increased proportionally over the dose range of 30 to 800 mg QD. The relationship between short-term VL change and GSK2248761 PK was best described by a maximum-effect (E(max)) model using C(tau) (E(max) = 2.0; 50% effective concentration [EC(50)] = 36.9 ng/ml). No NNRTI resistance mutations emerged during the study. GSK2248761 at 100 to 800 mg QD for 7 days was well tolerated, demonstrated potent antiviral activity in treatment-naive HIV-infected subjects, and had favorable PK and resistance profiles. GSK2248761 is no longer in clinical development. PMID- 22314533 TI - The F423Y mutation in the pfmdr2 gene and mutations N51I, C59R, and S108N in the pfdhfr gene are independently associated with pyrimethamine resistance in Plasmodium falciparum isolates. AB - Screening for in vitro susceptibility to pyrimethamine and sequencing of the pfmdr2 and pfdhfr genes were performed in 140 Plasmodium falciparum isolates. The risk of in vitro resistance to pyrimethamine was analyzed with a logistic regression model. The mutation F423Y in pfmdr2 (odds ratio [OR] = 2.12 [confidence interval {CI}, 1.02 to 4.59]; P = 0.0489) and the mutation N51I, C59R, or S108N in pfdhfr (OR = 42.34 [CI, 5.52 to 324.61]; P = 0.0003) were independently associated with in vitro resistance to pyrimethamine. PMID- 22314534 TI - Antibiotic exposure as a risk factor for fluconazole-resistant Candida bloodstream infection. AB - Recent exposure to azoles is an important risk factor for infection with fluconazole-resistant Candida spp., but little is known about the role of antibacterial drug exposure in the emergence of drug-resistant Candida. We did a prospective nationwide surveillance study of candidemia in Israel and analyzed the propensity score-adjusted association between antifungal and antibacterial drug exposure and bloodstream infection with C. glabrata and fluconazole resistant Candida isolates. Four hundred forty-four episodes of candidemia (450 Candida isolates, 69 [15%] C. glabrata isolates, and 38 [8.5%] fluconazole resistant isolates) from 18 medical centers in Israel were included. C. glabrata bloodstream infection was strongly associated with recent metronidazole exposure (odds ratio [OR], 3.2; P < 0.001). Infection with a fluconazole-resistant isolate was associated with exposure to carbapenems, trimethoprim-sulfamethoxazole, clindamycin, and colistin (odds ratio, 2.8; P = 0.01). The inclusion of antibacterial drug exposure in a multivariable model significantly enhanced the model's predictive accuracy for fluconazole-resistant Candida bloodstream infection. Our findings may be relevant to the selection of empirical antifungal treatment and broaden the scope of antibiotic-associated collateral damage. PMID- 22314535 TI - Expression turnover profiling to monitor the antifungal activities of amphotericin B, voriconazole, and micafungin against Aspergillus fumigatus. AB - Eight highly expressed candidate genes were selected for mRNA profiling to monitor the transcriptome kinetics of Aspergillus fumigatus strains exposed to antifungal drugs as potential biomarkers of live cells to assess treatment efficacy. Mycelia were treated with fungicidal drugs amphotericin B and voriconazole, as well as the fungistatic drug micafungin. Transcription was monitored at 0, 4, 8, and 24 h posttreatment. The expression turnover profile provides a possible tool to assess antifungal therapy effects. PMID- 22314536 TI - Wild coastline birds as reservoirs of broad-spectrum-beta-lactamase-producing Enterobacteriaceae in Miami Beach, Florida. AB - A high rate of broad-spectrum-beta-lactamase-producing Escherichia coli isolates was identified from seagull and pelican feces collected in the Miami Beach, Florida, area. The most commonly identified resistance determinants were CMY-2 and CTX-M-15. Those wild birds might be therefore considered vehicles for wide dissemination of multidrug-resistant Enterobacteriaceae in the United States. PMID- 22314537 TI - Ajoene, a sulfur-rich molecule from garlic, inhibits genes controlled by quorum sensing. AB - In relation to emerging multiresistant bacteria, development of antimicrobials and new treatment strategies of infections should be expected to become a high priority research area. Quorum sensing (QS), a communication system used by pathogenic bacteria like Pseudomonas aeruginosa to synchronize the expression of specific genes involved in pathogenicity, is a possible drug target. Previous in vitro and in vivo studies revealed a significant inhibition of P. aeruginosa QS by crude garlic extract. By bioassay-guided fractionation of garlic extracts, we determined the primary QS inhibitor present in garlic to be ajoene, a sulfur containing compound with potential as an antipathogenic drug. By comprehensive in vitro and in vivo studies, the effect of synthetic ajoene toward P. aeruginosa was elucidated. DNA microarray studies of ajoene-treated P. aeruginosa cultures revealed a concentration-dependent attenuation of a few but central QS-controlled virulence factors, including rhamnolipid. Furthermore, ajoene treatment of in vitro biofilms demonstrated a clear synergistic, antimicrobial effect with tobramycin on biofilm killing and a cease in lytic necrosis of polymorphonuclear leukocytes. Furthermore, in a mouse model of pulmonary infection, a significant clearing of infecting P. aeruginosa was detected in ajoene-treated mice compared to a nontreated control group. This study adds to the list of examples demonstrating the potential of QS-interfering compounds in the treatment of bacterial infections. PMID- 22314538 TI - Comparative efficacies of artemisinin combination therapies in Plasmodium falciparum malaria and polymorphism of pfATPase6, pfcrt, pfdhfr, and pfdhps genes in tea gardens of Jalpaiguri District, India. AB - In India, chloroquine has been replaced by a combination of artesunate and sulfadoxine-pyrimethamine (AS-SP) for uncomplicated P. falciparum malaria. Other available combinations, artemether-lumefantrine (AM-LF) and artesunate-mefloquine (AS-MQ), not included in the national program, are widely used by private practitioners. Little is known about the therapeutic efficacy of these artemisinin combinations and the prevalence of molecular markers associated with antimalarial drug resistance. A total of 157 patients with P. falciparum monoinfection were recruited and randomized into three study groups (AS-SP, AM LF, and AS-MQ). All patients were followed up for 42 days to study the clinical and parasitological responses according to the WHO protocol (2009). We assessed the polymorphism of the pfATPase6, pfcrt, pfdhfr, and pfdhps genes by the DNA sequencing method. The PCR-corrected therapeutic efficacies of AS-SP, AM-LF, and AS-MQ were 90.6% (95% confidence interval [CI], 0.793 to 0.969), 95.9% (95% CI, 0.860 to 0.995), and 100% (95% CI, 0.927 to 1.00), respectively. No specific mutational pattern was observed in the pfATPase6 gene. All isolates had a K76T mutation in the pfcrt gene. In the pfdhfr-pfdhps genotype, quadruple mutation was frequent, and quintuple mutation was documented in 6.3% of P. falciparum isolates. The significant failure rate of AS-SP (9.5%), although within the limit (10%) for drug policy change, was due to SP failure because of prevailing mutations in pfdhfr, I(51)R(59)N(108), with pfdhps, G(437) and/or E(540). The efficacy of this ACT needs periodic monitoring. Artemether-lumefantrine and artesunate-mefloquine are effective alternatives to the artesunate-sulfadoxine pyrimethamine combination. PMID- 22314539 TI - The T788G mutation in the cyp51C gene confers voriconazole resistance in Aspergillus flavus causing aspergillosis. AB - With voriconazole (VRC) being approved as the first choice in treating invasive aspergillosis (IA) and its increasing use in treatment, a VRC-resistant strain of Aspergillus flavus, the second leading cause of IA after Aspergillus fumigatus, has emerged. The VRC-resistant strain of A. flavus was isolated for the first time from the surgical lung specimen of an IA patient with no response to VRC therapy. In order to ascertain the mechanism of VRC resistance, the azole target enzyme genes in this strain of A. flavus were cloned and sequenced, and 4 mutations generating amino acid residue substitutions were found in the cyp51C gene. To further determine the role of this mutated gene for VRC resistance in A. flavus, an Agrobacterium tumefaciens-mediated gene replacement approach was applied. Consequently, the mutated cyp51C gene from this A. flavus strain was proven to confer the VRC resistance. Finally, to discern the one out of the four mutations in the cyp51C gene that is responsible for contributing to VRC resistance, a site-directed gene mutagenesis procedure combined with a gene replacement method was performed. As a result, the T788G missense mutation in the cyp51C gene was identified as responsible for VRC resistance in A. flavus. These findings indicated that the detection of this mutation in A. flavus could serve as an indicator for physicians to avoid the use of VRC during IA treatment. Further comprehensive surveillance for antifungal susceptibility, as well as intensive study on the mechanism of azole resistance in A. flavus causing IA, would be required to fully understand this mechanism. PMID- 22314540 TI - The lower prevalence of female genital mutilation in the Netherlands: a nationwide study in Dutch midwifery practices. AB - OBJECTIVES: To determine the prevalence of female genital mutilation (FGM) in women giving birth in 2008 in the Netherlands. METHOD: A retrospective questionnaire study was conducted.The study covered all 513 midwifery practices in the Netherlands. The data were analysed with SPSS 17.0. RESULTS: The response from midwifery practices was 93%(n = 478). They retrospectively reported 470 circumcised women in 2008 (0.32%). The expected prevalence in the Netherlands based on the estimated prevalence of FGM in the country of birth was 0.7%. It is likely that there was under reporting in midwifery practices since midwives do not always enquire about the subject and may not notice the milder types of FGM. Midwives who checked their records before answering our questionnaire reported a prevalence of 0.8%. CONCLUSION: On the basis of this study, we can conclude that FGM is a serious clinical problem in Europe for migrant women from risk countries for FGM. These women should receive extra attention from obstetricians and midwives during childbirth, since almost half are mutilated and FGM involves a risk of complications during delivery for both women and children. PMID- 22314541 TI - Smokers' compliance with smoke-free policies, and non-smokers' assertiveness for smoke-free air in the workplace: a study from the Balkans. AB - OBJECTIVE: Identify the psychosocial variables that predict smokers' compliance with smoke-free policies at work, and non-smokers' assertiveness for smoke-free rights in Greek and Bulgarian workplaces. METHODS: Data were collected from employees in Greece and Bulgaria. The main outcome measures were smokers' compliance with smoke-free policies, and non-smokers' assertiveness intentions. Demographic variables, tobacco use and dependence, as well as beliefs about second-hand smoke (SHS) exposure and smoking at work were also assessed. RESULTS: Regression analyses showed that smokers' compliance with smoke-free policies was predicted by age, perceived health risks of smoking, and beliefs related to the benefits of smoking at work. Non-smokers' assertiveness was predicted by annoyance from exposure to SHS at work, and assertiveness-related social cognitions (e.g., attitudes, social norms, and self-efficacy). CONCLUSIONS: Interventions to promote support for tobacco control policies at work in Greece and Bulgaria may benefit from targeting smokers' beliefs about the actual effects of tobacco use on health and job performance. Accordingly, efforts to promote non smokers assertiveness should build stronger assertiveness-related attitudes, convey anti-smoking normative messages, and strengthen self-efficacy skills. PMID- 22314542 TI - Prevalence of self-reported cardiovascular risk factors in Portuguese women: a survey after delivery. AB - OBJECTIVES: To estimate the pre-pregnancy prevalence of overweight/obesity, smoking, hypertension, dyslipidemia and diabetes mellitus, in women who delivered a live born. METHODS: In a birth cohort study, puerperae were consecutively recruited at five public maternities of Porto, Portugal (2005-2006). We included 7,381 women with complete data for the current analysis. Socioeconomic characteristics, smoking habits, pre-pregnancy weight and chronic diseases diagnosis were self-reported and height was measured. RESULTS: Before pregnancy, 21.3% of women were overweight and 8.8% were obese, 26.6% smoked and 11.2% were former smokers. The prevalence of hypertension, dyslipidemia and diabetes mellitus was 1.7, 1.7 and 0.6%, respectively, with an evident tendency to cluster. The prevalence of all cardiovascular risk factors, except smoking, increased with age and body mass index. Education and income were inversely associated with excessive weight. Current smokers were younger, thinner and in a lower socioeconomic position, whereas former smokers were older and in a higher socioeconomic position. CONCLUSION: Despite the low prevalence of hypertension, dyslipidemia and diabetes, their tendency to cluster and the increased prevalence among overweight/obese women highlight the high level of risk of this young female population. PMID- 22314543 TI - Regional deprivation in Bavaria, Germany: linking a new deprivation score with registry data for lung and colorectal cancer. AB - OBJECTIVE: This study aimed to examine the differences in cancer risk by regional deprivation in Bavaria, Germany. METHODS: Multilevel Poisson regression analysis was used to evaluate the association between lung and colorectal cancer risk and community deprivation level based on data from the Cancer Registry of Bavaria (2003-2006). The communities (n=1,408) were classified according to the Bavarian Index of Multiple Deprivation (BIMD), differentiated into quintiles ranging from lowest to highest deprivation. RESULTS: Increased lung cancer risk in men and colorectal cancer risk in both genders were associated with increasing BIMD. Comparing the most deprived with the least deprived communities, the relative risk for lung cancer incidence in men was 1.39 (95% CI 1.29-1.49), for mortality risk 1.54 (95% CI 1.41-1.68). The relative risk for colorectal cancer incidence in men was 1.30 (95% CI 1.22-1.38) and in women 1.19 (95% CI 1.11-1.27); for mortality risk we found 1.57 (95% CI 1.40-1.76) in men and 1.34 (95% CI 1.19 1.51) in women. CONCLUSION: Area-based deprivation is significantly associated with cancer risk in Bavaria. PMID- 22314544 TI - Socioeconomic status and incident cardiovascular disease in a developing country: findings from the Isfahan cohort study (ICS). AB - OBJECTIVES: We evaluated the association between socioeconomic status (SES) and incident cardiovascular disease (CVD) in a sample of the Iranian population. METHODS: We followed 6,504 participants who were initially free from CVD. At baseline, subjects were assessed for CVD risk factors and self-reported data were obtained for education, occupation, and income. RESULTS: After 24,379 person years of follow-up (median = 4.8 years), 276 incident cases of CVD were detected. There was no significant association between the level of education and the incidence of CVD. In univariate analysis, retired individuals showed a significantly higher incidence of CVD than individuals who were working, and subjects in the highest tertile of income were less likely to suffer CVD than those in the lowest tertile. However, the associations disappeared after adjusting for age and sex. DISCUSSION: There was no detectable, independent association between the SES and incident CVD. The counterbalance of the higher exposure to CVD risk factors and better access to health-care services and more appropriate risk factor modification in higher socioeconomic classes might diminish the association of SES and CVD in developing countries. PMID- 22314545 TI - Perceived teacher unfairness and headache in adolescence: a cross-national comparison. AB - OBJECTIVES: The present study examines the prevalence of headache in early adolescents in 21 European and North-American countries and the role of perceived teacher unfairness in predicting this health complaint across different countries. METHODS: Data were taken from the "Health Behaviour in School-aged Children" study (HBSC), a World Health Organization cross-national survey on health behaviors in 11-, 13- and 15-year-old students. Headache and perceived teacher unfairness were measured through a self-administered questionnaire filled out by 115,212 adolescents. RESULTS: The overall prevalence of frequent headaches (at least once a week) was 28.8%, ranging from 18.9% in Slovenia to 49.4% in Israel. After adjusting for gender, grade, family affluence, school achievement, being bullied and lifestyles (drinking, smoking, eating and physical activity), teacher unfairness showed a significant association with frequent headache in all but two countries (Ukraine and Luxembourg). CONCLUSIONS: Our results show that headache is a common health symptom in European and North-American countries, even though there are substantial differences in its prevalence across countries. The study indicates that perceived teacher unfairness can be a significant predictor of frequent headache during adolescence, and this association is consistent across countries. PMID- 22314546 TI - Effects of time-dependent stimuli in a competitive neural network model of perceptual rivalry. AB - We analyze a competitive neural network model of perceptual rivalry that receives time-varying inputs. Time-dependence of inputs can be discrete or smooth. Spike frequency adaptation provides negative feedback that generates network oscillations when inputs are constant in time. Oscillations that resemble perceptual rivalry involve only one population being "ON" at a time, which represents the dominance of a single percept at a time. As shown in Laing and Chow (J. Comput. Neurosci. 12(1):39-53, 2002), for sufficiently high contrast, one can derive relationships between dominance times and contrast that agree with Levelt's propositions (Levelt in On binocular rivalry, 1965). Time-dependent stimuli give rise to novel network oscillations where both, one, or neither populations are "ON" at any given time. When a single population receives an interrupted stimulus, the fundamental mode of behavior we find is phase-locking, where the temporally driven population locks its state to the stimulus. Other behaviors are analyzed as bifurcations from this forced oscillation, using fast/slow analysis that exploits the slow timescale of adaptation. When both populations receive time-varying input, we find mixtures of fusion and sole population dominance, and we partition parameter space into particular oscillation types. Finally, when a single population's input contrast is smoothly varied in time, 1:n mode-locked states arise through period-adding bifurcations beyond phase-locking. Our results provide several testable predictions for future psychophysical experiments on perceptual rivalry. PMID- 22314548 TI - Vibrationally resolved circular dichroism spectra of a molecule with isotopically engendered chirality. AB - We present a theoretical study of vibrationally resolved circular dichroism spectra, both in the adiabatic and non-adiabatic frameworks, with a full account of Franck-Condon and Herzberg-Teller vibrational contributions for the former. Model calculations have been performed on 2(R)-deuteriocyclopentanone, whose chirality is due solely to isotopic substitution. This molecule has two distinct, nearly isoenergetic, half-chair conformations in equilibrium, and its demanding nature in terms of computational accuracy makes it a perfect candidate for performing a detailed comparison between different vibronic models. Comparisons are made with experimental spectra, and we also consider temperature effects. In order to reproduce the experimental spectrum, it is necessary to consider the geometry relaxation occurring during the n->pi* transition. PMID- 22314549 TI - Vapor diffusion sol-gel synthesis of fluorescent perovskite oxide nanocrystals. AB - A model system consisting of Eu(3+) as the activator ion and BaZrO(3) as the host lattice is employed to demonstrate the potential of the vapor diffusion sol-gel method as a hydrolytic approach to the synthesis of fluorescent alkaline-earth perovskite oxide nanocrystals under ultrabenign conditions. The resulting nanocrystals are suitable precursors for nanostructured red-emitting phosphors. PMID- 22314550 TI - Vortex fluidic exfoliation of graphite and boron nitride. AB - Graphite is exfoliated into graphene by shearing vortex fluidic films of N-methyl pyrrolidone (NMP), as a controlled process for preparing oxide free graphene, and for exfoliating the corresponding boron nitride sheets. PMID- 22314551 TI - Reprogramming of prostate cancer-associated stromal cells to embryonic stem-like. AB - BACKGROUND: CD90(+) prostate cancer-associated (CP) stromal cells represent a diseased cell type found only in tumor tissue. They differ from their normal counterpart in gene expression and inductive signaling. Genetic reprogramming by induced pluripotent stem (iPS) cell technology can effectively change adult cells into stem-like cells through wholesale alteration of the gene expression program. This technology might be used to 'erase' the abnormal gene expression of diseased cells. The resultant iPS cells would no longer express the disease phenotype, and behave like stem cells. METHODS: CP stromal cells, isolated from tumor tissue of a surgically resected prostate by anti-CD90-mediated sorting and cultured in vitro, were transfected with in vitro packaged lentiviral expression vectors containing stem cell transcription factor genes POU5F1, LIN28, NANOG, and SOX2. RESULTS: Alkaline phosphatase-positive iPS cells were obtained in about 3 weeks post-transfection at a frequency of 10(-4) . Their colony morphology was indistinguishable from that of human embryonic stem (ES) cells. Transcriptome analysis showed a virtually complete match in gene expression between the iPS and ES cells. CONCLUSIONS: Genes of CP stromal cells could be fully inactivated by genetic reprogramming. As a consequence, the disease phenotype was 'cured'. PMID- 22314552 TI - Modern electroencephalography. AB - Electroencephalography (EEG) has been in continuous development over at least 70 years and is firmly established as a tool in the management of epilepsy. For a while, the technique fell into disregard because of difficulties with interpretation, specificity and sensitivity. Whilst clinicians have to be aware of these problems, they have been largely addressed by recent computer digitization of signals, which permits longer standard recordings and monitoring linked to a simultaneous video. These techniques are not only an essential component of a specialist epilepsy service, where inpatient video-EEG telemetry is vital both for diagnosis and assessment before neurosurgical treatment, but also in general and acute medical settings, particularly for the management of status epilepticus. Further developments in computing will extend the use of EEG in all of these roles and long-term monitoring for diagnosis and management of coma will become more widely available. PMID- 22314553 TI - Correlation between clinical outcomes and appropriateness grading for referral to myocardial perfusion imaging for preoperative evaluation prior to non-cardiac surgery. AB - BACKGROUND: In a previous study, we have found that referral to myocardial perfusion imaging(MPI) for preoperative evaluation of patients before non-cardiac surgery was the most common cause of inappropriate referral based on AHA/ACC Appropriate Use Guidelines, though 40% of scans graded as inappropriate had abnormal MPI results. The aim of this study was to correlate appropriateness grading with (1) the outcome of MPI scans, and (2) the clinical outcome of patients after surgery, so as to determine if the predictive value of MPI was related to appropriateness grading. METHODS: All consecutive patients referred to the MPI laboratory of our center from March 2009 to July 2009 for preoperative risk stratification were prospectively studied. Patients' medical records and stress data were collected, and all imaging results were recorded. Based on appropriate use criteria (AUC), MPI studies were classified into appropriate, inappropriate, uncertain or unclassified. MPI studies were classified on the basis of their results into normal or abnormal scans. Primary clinical outcome measured was the occurrence of any major cardiac and cerebrovascular event during follow-up up to 90 days. RESULTS: There were 176 referrals for preoperative evaluation. 39.8% (n 5 70) of these referrals were graded as inappropriate. Based on AUC, referrals for MPI in intermediate- and high-risk groups with poor functional class were graded as appropriate, while referrals for MPI in low-risk and intermediate risk groups with normal functional class were graded as inappropriate referrals. The overall event rate was 6.25%. Cumulative death rate at 90 days was 1.7%, non-fatal MI 4%, and occurrence of stroke occurred in 0.6%. The primary outcome was higher in the intermediate group with poor functional class (13%) and high-risk group (64%) than the low-risk and intermediate risk groups with good functional class (4%). In the high-risk group, an abnormal MPI scan was associated with an extremely high event rate (50%) that was significantly greater than the event rate in patients with a normal MPI result (14%) (P 5 .01). Although 40% of preoperative low-risk and intermediate risk patients had an abnormal MPI result, their over all event rates were low (0 and 4%, respectively), with no difference in the rate of events between patients with normal and abnormal MPI scans in the inappropriate group. CONCLUSIONS: In conclusion, in correlating the relationship between appropriateness grading by AUC with the outcome of MPI scans and subsequent event rates, we found that MPI results predicted outcome in appropriately tested patients, but not in patients whose tests were classified as inappropriate, in whom event rates were low, regardless of the results of testing. Our findings support the AUC recommendations for the selective role of testing in preoperative risk stratification,which use the type of surgery and functional class to determine the appropriateness of referral. PMID- 22314554 TI - Effects of patient movement on measurements of myocardial blood flow and viability in resting 15O-water PET studies. AB - BACKGROUND: Patient movement has been considered an important source of errors in cardiac PET. This study was aimed at evaluating the effects of such movement on myocardial blood flow (MBF) and perfusable tissue fraction (PTF) measurements in intravenous 15O-water PET. METHODS: Nineteen 15O-water scans were performed on ten healthy volunteers and three patients with severe cardiac dysfunction under resting conditions. Motions of subjects during scans were estimated by monitoring locations of markers on their chests using an optical motion-tracking device. Each sinogram of the dynamic emission frames was corrected for subject motion. Variation of regional MBF and PTF with and without the motion corrections was evaluated. RESULTS: In nine scans, motions during 15O-water scan (inter-frame (IF) motion) and misalignments relative to the transmission scan (inter-scan (IS) motion) larger than the spatial resolution of the PET scanner (4.0 mm) were both detected by the optical motion-tracking device. After correction for IF motions, MBF values changed from 0.845 +/- 0.366 to 0.780 +/- 0.360 mL/minute/g (P < .05). In four scans with only IS motion detected, PTF values changed significantly from 0.465 +/- 0.118 to 0.504 +/- 0.087 g/mL (P< .05), but no significant change was found in MBF values. CONCLUSIONS: This study demonstrates that IF motion during 15O-water scan at rest can be source of error in MBF measurement. Furthermore, estimated MBF is less sensitive than PTF values to misalignment between transmission and 15O-water emission scans. PMID- 22314555 TI - Acute hyperglycemia causes microvascular damage, leading to poor functional recovery and remodeling in patients with reperfused ST-segment elevation myocardial infarction. AB - BACKGROUND: Although acute hyperglycemia (AHG) is associated with poor outcomes in ST-segment elevation myocardial infarction (STEMI) patients, underlying mechanisms have not been fully elucidated. We investigated the influence of AHG on myocardial microcirculation in reperfused STEMI patients. METHODS AND RESULTS: Thirty-four STEMI patients were divided into 2 groups according to the presence (Group H, n 5 11) or the absence (Group L, n 5 23) of AHG. Myocardial blood flow (MBF) and myocardial flow reserve (MFR) in the infarct-related area were compared between 2 groups, using 13N-ammonia positron emission tomography. Wall motion abnormality scores (WMASs) and end-diastolic volume indices (EDVI) were also assessed at 1 and 6 months after the onset. Although resting MBF was similar, MFR was lower in Group H than in Group L (1.69 +/- 0.37 vs 2.39 +/- 0.56, P = .001). WMAS was greater in Group H than in Group L at both 1 month (7.4 +/- 3.7 vs 3.7 +/- 3.0, P = .011) and 6 months (7.3 +/- 3.9 vs 3.1 +/- 3.4, P = .015). EDVI tended to be greater in Group H than in Group L at 6 months (103.8 +/- 42.9 vs 73.9 +/- 16.0 mL/m2, P = .071). Multivariate analysis showed AHG to be independently associated with low MFR. CONCLUSIONS: In STEMI patients, AHG impaired myocardial microcirculation, leading to poor functional recovery and remodeling despite successful reperfusion. PMID- 22314556 TI - Organotypic slice cultures of embryonic ventral midbrain: a system to study dopaminergic neuronal development in vitro. AB - The mouse is an excellent model organism to study mammalian brain development due to the abundance of molecular and genetic data. However, the developing mouse brain is not suitable for easy manipulation and imaging in vivo since the mouse embryo is inaccessible and opaque. Organotypic slice cultures of embryonic brains are therefore widely used to study murine brain development in vitro. Ex vivo manipulation or the use of transgenic mice allows the modification of gene expression so that subpopulations of neuronal or glial cells can be labeled with fluorescent proteins. The behavior of labeled cells can then be observed using time-lapse imaging. Time-lapse imaging has been particularly successful for studying cell behaviors that underlie the development of the cerebral cortex at late embryonic stages (1-2). Embryonic organotypic slice culture systems in brain regions outside of the forebrain are less well established. Therefore, the wealth of time-lapse imaging data describing neuronal cell migration is restricted to the forebrain (3,4). It is still not known, whether the principles discovered for the dorsal brain hold true for ventral brain areas. In the ventral brain, neurons are organized in neuronal clusters rather than layers and they often have to undergo complicated migratory trajectories to reach their final position. The ventral midbrain is not only a good model system for ventral brain development, but also contains neuronal populations such as dopaminergic neurons that are relevant in disease processes. While the function and degeneration of dopaminergic neurons has been investigated in great detail in the adult and ageing brain, little is known about the behavior of these neurons during their differentiation and migration phase (5). We describe here the generation of slice cultures from the embryonic day (E) 12.5 mouse ventral midbrain. These slice cultures are potentially suitable for monitoring dopaminergic neuron development over several days in vitro. We highlight the critical steps in generating brain slices at these early stages of embryonic development and discuss the conditions necessary for maintaining normal development of dopaminergic neurons in vitro. We also present results from time lapse imaging experiments. In these experiments, ventral midbrain precursors (including dopaminergic precursors) and their descendants were labeled in a mosaic manner using a Cre/loxP based inducible fate mapping system (6). PMID- 22314557 TI - Towards understanding the inherited susceptibility for nephropathy in diabetes. AB - PURPOSE OF REVIEW: The burden of nephropathy is unequally shared across patients with diabetes. The majority of the variability in incident nephropathy remains unaccounted for by conventional risk factors. There appears to be an inherited predisposition for diabetic nephropathy, but this does not follow simple Mendelian rules. Any inherited predisposition for nephropathy is far more complicated. This article reviews the recent advances in understanding of the genetics and epigenetics of diabetic nephropathy. RECENT FINDINGS: A few candidate genes have been reproducibly associated with diabetic nephropathy, and recent genome-wide linkage studies have also identified chromosomal loci for susceptibility genes, including 3q, 7q, 10p, 14q and 18q. Unbiased, genome-wide linkage studies have identified specific loci and genome-wide association studies a number of new loci. However, any roles of those genes in the molecular pathobiology remain to be established. Moreover, their individual contribution to the variability in incident nephropathy in diabetes appears to be small. SUMMARY: New genome-wide approaches offer new opportunities to identify genes associated with diabetic nephropathy. However, such approaches have key limitations. Upto the present time, genetic testing has failed to identify a gene or combination of genes that will substantially identify those patients most at risk for diabetic nephropathy. It may be that epigenetic regulation of gene expression may represent a more important contributor to an inherited predisposition to diabetic nephropathy. Nonetheless, genetic studies may provide valuable information regarding the pathobiology of nephropathy and potential targets for its treatment. PMID- 22314558 TI - Current world literature. PMID- 22314560 TI - Biostimulatory effect of low-level laser therapy on keratinocytes in vitro. AB - Epithelial cells play an important role in reparative events. Therefore, therapies that can stimulate the proliferation and metabolism of these cells could accelerate the healing process. To evaluate the effects of low-level laser therapy (LLLT), human keratinocytes were irradiated with an InGaAsP diode laser prototype (LASERTable; 780 +/- 3 nm; 40 mW) using 0.5, 1.5, 3, 5, and 7 J/cm2 energy doses. Irradiations were done every 24 h totaling three applications. Evaluation of cell metabolism (MTT assay) showed that LLLT with all energy doses promoted an increase of cell metabolism, being more effective for 0.5, 1.5, and 3 J/cm2. The highest cell counts (Trypan blue assay) were observed with 0.5, 3, and 5 J/cm2. No statistically significant difference for total protein (TP) production was observed and cell morphology analysis by scanning electron microscopy revealed that LLLT did not promote morphological alterations on the keratinocytes. Real-time polymerase chain reaction (qPCR) revealed that LLLT also promoted an increase of type I collagen (Col-I) and vascular endothelial growth factor (VEGF) gene expression, especially for 1.5 J/cm2, but no change on fibroblast growth factor-2 (FGF-2) expression was observed. LLLT at energy doses ranging from 0.5 to 3 J/cm2 promoted the most significant biostimulatory effects on cultured keratinocytes. PMID- 22314561 TI - Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options. AB - Stress, which is defined as an acute threat to homeostasis, shows both short- and long-term effects on the functions of the gastrointestinal tract. Exposure to stress results in alterations of the brain-gut interactions ("brain-gut axis") ultimately leading to the development of a broad array of gastrointestinal disorders including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and other functional gastrointestinal diseases, food antigen-related adverse responses, peptic ulcer and gastroesophageal reflux disease (GERD). The major effects of stress on gut physiology include: 1) alterations in gastrointestinal motility; 2) increase in visceral perception; 3) changes in gastrointestinal secretion; 4) increase in intestinal permeability; 5) negative effects on regenerative capacity of gastrointestinal mucosa and mucosal blood flow; and 6) negative effects on intestinal microbiota. Mast cells (MC) are important effectors of brain-gut axis that translate the stress signals into the release of a wide range of neurotransmitters and proinflammatory cytokines, which may profoundly affect the gastrointestinal physiology. IBS represents the most important gastrointestinal disorder in humans, and is characterized by chronic or recurrent pain associated with altered bowel motility. The diagnostic testing for IBS patients include routine blood tests, stool tests, celiac disease serology, abdominal sonography, breath testing to rule out carbohydrate (lactose, fructose, etc.) intolerance and small intestinal bacterial overgrowth. Colonoscopy is recommended if alarming symptoms are present or to obtain colonic biopsies especially in patients with diarrhoea predominant IBS. The management of IBS is based on a multifactorial approach and includes pharmacotherapy targeted against the predominant symptom, behavioural and psychological treatment, dietary alterations, education, reassurance and effective patient-physician relationship. When evaluating for the stress-induced condition in the upper GI tract, the diagnostic testing includes mainly blood tests and gastroscopy to rule out GERD and peptic ulcer disease. The therapy for these conditions is mainly based on the inhibition of gastric acid by proton pump inhibitors and eradication of Helicobacter pylori-infection. Additionally, melatonin an important mediator of brain gut axis has been shown to exhibit important protective effects against stress-induced lesions in the gastrointestinal tract. Finally, probiotics may profoundly affect the brain-gut interactions ("microbiome-gut-brain axis") and attenuate the development of stress-induced disorders in both the upper and lower gastrointestinal tract. Further studies on the brain-gut axis are needed to open new therapeutic avenues in the future. PMID- 22314562 TI - Cardioprotective role of sphingosine-1-phosphate. AB - Sphingosine-1-phosphate (S1P) has been shown to exert potent cardioprotective action. It binds to the plasma membrane receptors. Three S1P receptors are present in the heart: 1, 2 and 3. Exogenous S1P increases viability of cardiomyocytes incubated under hypoxic conditions. It also reduces the infarct size in isolated, perfused rat heart after ischemia/reperfusion. Formation of S1P in the heart is catalyzed by the enzyme sphingosine kinase 1 and its catabolism by the enzyme sphingosine1-phosphate lyase. Reduction in the activity of sphingosine kinase 1 or knocking out its gene eliminates cardioprotective effect of ischemic preconditioning in mice. Knocking out the sphingosine-1-phosphate lyase gene exerts potent cardioprotective effect against ischemia/reperfusion in the mouse heart. The following mechanism of cardioprotection by S1P is suggested: S1P binds to its membrane receptors and the complex activates protein G. Activated protein G activates PI3K which in turn activates pro-survival Akt kinase. S1P activates also Stat3, a powerful cardioprotectant. It should be added that ischemia/reperfusion increases markedly the myocardial content of two other sphingolipids, namely sphingosine and ceramide. Sphingosine, a direct precursor of S1P, in a high dose is cardiotoxic. Ceramide (the key sphingolipid, a precursor of sphingosine) is claimed to be responsible for activation of apoptosis during ischemia/reperfusion. Therefore, the two latter sphingolipids may counteract, to a certain degree, the cardioprotective action of S1P. It is suggested, that development of specific S1P agonists and compounds modifying activity of the two enzymes could provide important therapeutic tools in the treatment of the heart infarct. PMID- 22314563 TI - Gastric ulcerogenic and healing impairment effects of risedronate, a nitrogen containing bisphosphonate in rats. Comparison with alendronate and minodronate. AB - We examined the mucosal irritating and healing impairment effects of risedronate, a nitrogen-containing bisphosphonate (BPP), on rat stomachs, in comparison with those of alendronate and minodronate. Male SD rats were used in the following two studies; 1) the ulcerogenic effects of risedronate, alendronate and minodronate in the antral mucosa, and 2) the healing impairment effect of these drugs on gastric ulcers induced by thermocauterization. A single administration of BPPs to fasted rats produced ulcers in the antrum with severe edema and inflammation 3 days after refeeding, although the doses required for this action differed among these BPPs: alendronate >100 mg/kg, risedronate >300 mg/kg, minodronate >10 mg/kg. The generation of antral ulcers induced by these BPPs was accompanied by an increase in myeloperoxidase (MPO) activity and lipid peroxidation as well as a decrease in superoxide dismutase (SOD) activity and glutathione (GSH) content in the mucosa; the extent order of these changes was minodronate >alendronate >risedronate. On the other hand, the healing of gastric ulcers was significantly delayed by daily administration of alendronate (>30 mg/kg) and minodronate (>10 mg/kg), but not by risedronate, even at 60 mg/kg. Mucosal vascular endothelium derived growth factor (VEGF) and basic fibroblast growth factor (bFGF) protein expressions were up-regulated after ulceration, in parallel with angiogenesis. Alendronate and minodronate decreased these expressions and angiogenesis, while risedronate had no effect. In conclusion, the gastric adverse effect of risedronate is less potent than alendronate and minodronate. It is assumed that risedronate may be used more safely than other BPPs as an antiresorptive drug in patients. PMID- 22314564 TI - The healing of NSAID-induced gastric lesion may be followed by small intestinal and cardiovascular side effects. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) are among some of the most commonly used medications. Serious adverse effects induced by NSAIDs may occur not only in the upper gastrointestinal tract, but in the small intestine and cardiovascular system. However, these side effects are studied and investigated separately. Here we tested the hypothesis that the healing of indomethacin-induced gastric erosion may be followed by small intestinal and cardiovascular adverse effects. First we examined the development of gastrointestinal lesions 4-24-48-72 h after a single indomethacin (35 mg/kg s.c.) injection given to fasted male rats (refeeding after 4 h). Then with a telemetric device heart rate, core body temperature and locomotion changes were recorded in the freely moving animals for 72 h after indomethacin or its vehicle injection (control). Indomethacin produced hemorrhagic erosion in the glandular stomach 4 h after its administration which was almost completely healed 48 h later. Parallel to the healing a gradual increase of injury to the small intestine became apparent. The control rats' heart rate, core body temperature and locomotion all agreed with a normal circadian rhythm. However, the circadian cycle of rats treated with indomethacin in 24 h after its administration was disrupted: their heart rate rose to it's maximal level and their locomotion and core temperature values fell to their minimal. These results suggest that the healing of gastric erosion induced by a single indomethacin injection may be followed by other pathological events outside of the stomach, among which there may be intestinal injury and a loss of a normal circadian cycle of heart rate as well as body temperature and locomotion. PMID- 22314565 TI - Evidence-based therapy according to the guideline for gastric ulcers is cost effective in Japan. AB - Helicobacter pylori (H. pylori) infection is a major cause of gastric ulcers (GU) and eradication of the infection controls the ulcer with no requirement for maintenance therapy. In Japan, an evidence-based guideline (GL) was first published in 2003 (1(st) version) and then again in 2007 (2(nd) version) with a minor revision under support of the Japanese Ministry of Health, Labor and Welfare (GUGLJ). Adherence to its standards is high, estimated at 80%. GU patients aged 18 or older with active ulcers at the time of diagnosis by an endoscopic examination at National Hospital Organization (NHO) hospitals of Japan were enrolled between September 2004 and April 2005. Subjective and endoscopic outcome, medical treatments and medical costs during the following nine months were analyzed, retrospectively. As a result, 935 patients and 270 doctors in charge from 62 NHO hospitals were analyzed. Among H. pylori-positive GU patients, the endoscopic recurrence rate of 24 patients with failure of eradication was 29.2%, which was significantly higher than 8.8% of 194 patients with successful eradication. Successful eradication of H. pylori resulted in significantly lower endoscopic recurrence rates for GU patients either with or without administration of non-steroidal anti-inflammatory drugs (NSAID). GUGLJ adherence scores were significantly related to the specialty or knowledge on the GUGLJ of doctors in charge, and the total medical cost consumed. These results suggest that the therapy of GU along with an evidence-based GL is essential to implement cost effective treatment and the GI experts or the doctors that understand the GUGLJ very well should perform it. PMID- 22314566 TI - Electrical vagus nerve stimulation decreases food consumption and weight gain in rats fed a high-fat diet. AB - There is growing evidence that vagus nerve stimulation (VNS) has a suppressive effect on both short- and long-term feeding in animal models. We previously showed that long-term VNS (102 days) with low-frequency electrical impulses (0.05 Hz) decreased food intake and body weight in rats. In the present study, we investigated the effect of high frequency (10 Hz) VNS on feeding behavior and appetite in rats fed a high-fat diet; peptide secretion and other parameters were assessed as well. Adult male Wistar rats were each implanted subcutaneously with a microstimulator (MS) and fed a high-fat diet throughout the entire study period (42 days). The left vagus nerve was stimulated by rectangular electrical pulses (10 ms, 200 mV, 10 Hz, 12 h a day) generated by the MS. Body weight and food intake were measured each morning. At the end of the experimental period, animals were euthanized and blood samples were taken. Serum levels of ghrelin, leptin and nesfatin-1 were assessed using radioimmunoassays. Adipose tissue content was evaluated by weighing epididymal fat pads, which were incised at the time of sacrifice. To determine whether VNS activated the food-related areas of the brain, neuronal c-Fos induction in the nuclei of the solitary tract (NTS) was assessed. Chronic vagus nerve stimulation significantly decreased food intake, body weight gain and epididymal fat pad weight in animals that received VNS compared with control animals. Significant neuronal responses in the NTS were observed following VNS. Finally, serum concentrations of ghrelin were increased, while serum levels of leptin were decreased. Although not significant, serum nesfatin-1 levels were also elevated. These results support the theory that VNS leads to reductions in food intake, body weight gain and adipose tissue by increasing brain satiety signals conducted through the vagal afferents. VNS also evoked a feed-related hormonal response, including elevated blood concentrations of nesfatin-1. PMID- 22314567 TI - Association of the physical activity with leptin blood serum level, body mass indices and obesity in schoolgirls. AB - Decreased physical activity is undoubtedly significantly associated with obesity. Similarly, the proper hormones secretion, the proper weight and body development. The aim of this study was to investigate the relationship between body mass composition and leptin concentration in relation to the degree of physical activity expressed in MET-h/week (metabolic equivalent per week). The study included 59 girls, aged 9-16 years (12.55+/-1.67) and divided into two groups: 1) PA: a physically active group of 29 girls and 2) PI: a group of 30 physically inactive girls. In all, physical activity was assessed using modified questionnaire concerning "activity for adolescents" and expressed in MET-h/week. Serum blood leptin concentrations in fasting girls were determined by RIA. Anthropometric parameters were measured and fatness indices calculated (BMI, SF, WHtR). Body composition (%BF, FM, FFM) was assessed using bioelectrical impedance analysis method (BIA). Statistical analysis showed significant differences between groups of PA and PI concerning values of BMI, WHtR, %BF, WC and MET h/week as well as in leptin concentrations. In both groups of girls negative correlations between physical activity measured in MET and leptin concentrations and in WHtR were observed. The concentration of leptin was directly proportional to the degree of body fat and to the body composition expressed by BMI, WHtR, log SF, WC and %BF, FM and FFM, respectively. Increased physical activity was associated with lower body fat ratios and WHtR, BMI, WC, %BF, but did not affect significantly the changes in the values of log SF, FM and FFM. Higher values of BMI, WHtR and WC can provide not only a greater risk of obesity in general, but also cause excessive accumulation of fat in the central part of the body (abdominal obesity). PMID- 22314568 TI - Effects of extremely low frequency magnetic field on oxidative balance in brain of rats. AB - Extremely low frequency magnetic field (ELF-MF) may result in oxidative DNA damage and lipid peroxidation with an ultimate effect on a number of systemic disturbances and cell death. The aim of the study is to assess the effect of ELF MF parameters most frequently used in magnetotherapy on reactive oxygen species generation (ROS) in brain tissue of experimental animals depending on the time of exposure to this field. The research material included adult male Sprague-Dawley rats, aged 3-4 months. The animals were divided into 3 groups: I - control (shame) group; II - exposed to the following parameters of the magnetic field: 7 mT, 40 Hz, 30 min/day, 10 days; III - exposed to the ELF-MF parameters of 7 mT, 40 Hz, 60 min/day, 10 days. The selected parameters of oxidative stress: thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H(2)O(2)), total free sulphydryl groups (-SH groups) and protein in brain homogenates were measured after the exposure of rats to the magnetic field. ELF-MF parameters of 7 mT, 40 Hz, 30 min/day for 10 days caused a significant increase in lipid peroxidation and insignificant increase in H(2)O(2) and free -SH groups. The same ELF-MF parameters but applied for 60 min/day caused a significant increase in free -SH groups and protein concentration in the brain homogenates indicating the adaptive mechanism. The study has shown that ELF-MF applied for 30 min/day for 10 days can affect free radical generation in the brain. Prolongation of the exposure to ELF-MF (60/min/day) caused adaptation to this field. The effect of ELF-MF irradiation on oxidative stress parameters depends on the time of animal exposure to magnetic field. PMID- 22314569 TI - The 5-HT(7) receptor antagonist SB 269970 counteracts restraint stress-induced attenuation of long-term potentiation in rat frontal cortex. AB - The effects of restraint lasting for 10 min, repeated twice daily for 3 days, were studied ex vivo in rat frontal cortex slices prepared 24 h after the last stress session. In slices originating from stressed animals, the amplitude of extracellular field potentials recorded in cortical layer II/III was increased. Stress also resulted in a reduced magnitude of long-term potentiation (LTP) of field potentials. In a separate experimental group, rats were subjected to restraint lasting for 10 min, twice daily for 3 days but, additionally, animals received injections of 5-HT(7) receptor antagonist SB 269970 (1.25 mg/kg) before each restraint stress session. In this group, the amplitude of field potentials and the magnitude of LTP were not different from the control, indicating that stress-induced modifications of basal glutamatergic transmission and synaptic plasticity were prevented by the 5-HT(7) receptor antagonist. PMID- 22314570 TI - Antipyretic activity of N-acetylcysteine. AB - N-acetylcysteine (NAC) has been used primarily as a mucolytic agent for the treatment of respiratory diseases. It has been recently suggested that NAC also possesses some anti-inflammatory properties. The aim of the present study is to investigate the effects of NAC on fever provoked either by bacterial lipopolysaccharide (LPS) or a turpentine-induced aseptic abscess in the rats. The body temperature (Tb) and the motor activity of the Wistar rats were measured using biotelemetry system. NAC (200 mg/kg) was injected intraperitoneally (i.p.) One hour prior to the injection of LPS (50 MUg/kg; i.p.) or turpentine (100 MUl/rat; subcutaneously) into separate groups of rats. The injection of NAC into normal non-febrile rats did not alter the animal circadian rhythm in Tb and activity. Pretreatment of rats with NAC resulted in the reduction of both infectious and aseptic fevers. Fever in rats was associated with inhibition of the motor activity and loss of body weight. Treatment with NAC diminished the decrease of motor activity and had no effect on the reduction of body weight in rats injected with LPS. It did, however, attenuate the drop of body mass in rats challenged with turpentine oil. Based on these data one may conclude that NAC, in addition to its mucolytic, antioxidant and anti-inflammatory properties, may be considered as a therapeutic fever-modulating agent under certain clinical circumstances. PMID- 22314571 TI - 6-methoxytryptophol reduces lipopolysaccharide-induced lipid peroxidation in vitro more effectively than melatonin. AB - Bacterial lipopolysaccharide (LPS) causes lipid peroxidation (LPO). We have found that LPS induces LPO in tissue homogenates in vitro in a concentration-dependent manner, the concentration of 400 MUg/ml demonstrating the most efficient lipid damaging effect. Antioxidant properties of melatonin are unquestionable and have been proved both in vivo and in vitro. It has been demonstrated that also melatonin metabolites and derivatives inhibit oxidative stress. The aim of our study was to compare the effects of melatonin (MEL) and indole compound: 6 methoxytryptophol, on LPS-induced LPO in vitro. Malondialdehyde (MDA) plus 4 hydroxyalkenal (4-HDA) concentrations were measured as the indicators of induced membrane peroxidative damage in brain, liver and kidney homogenates. Both melatonin and 6-methoxytryptophol were used at increasing concentrations, starting from 0.01-5 mM, together with LPS at one concentration of 400 MUg/ml. In all the examined tissues, LPS stimulated LPO, while both melatonin and 6 methoxytryptophol released LPS-stimulated LPO. Furthermore, the capacity of 6 methoxytryptophol reducing LPO was higher than that of melatonin. The results of the reported study clearly indicate that 6-methoxytryptophol is a much stronger antioxidant in vitro than melatonin in terms of reducing oxidative damage to lipid membranes. However, it remains still unclear how the features relate to in vivo circumstances. PMID- 22314572 TI - Protective effect of oral Lactobacilli in pathogenesis of chronic periodontitis. AB - The study aimed at evaluation of IL-17 and TNF-alpha levels and at analysis of oral lactobacilli in patients with chronic periodontitis (CP) in the context of their protective effect on a course of the disease. The study was conducted on 14 patients with moderate CP (group 1) and 14 patients with severe CP (group 2). Control group (group 3) included 15 individuals with gingivitis. Levels of IL-17 and TNF-alpha were estimated using an ELISA. Strains of Lactobacillus were isolated in Rogosa agar, H(2)O(2)-production was determined in TMB-Plus agar. In group 1, the mean content of IL-17 was 19.66+/-6.1 pg/ml, and that of TNF-alpha was 4.95+/-0.91 pg/ml, in group 2 IL-17 content was 34.7+/-6.65 pg/ml, and that of TNF-alpha was 6.94+/-0.78pg/ml, in group 3 content of IL-17 was 0.65+/ 0.58pg/ml, content of TNF-alpha was 0.17+/-0.14pg/ml. Analysis of lactobacilli manifestation in the control group and in the group with moderate CP in most of the persons demonstrated presence of H(2)O(2)-producing Lactobacillus, while in the group with severe CP presence of Lactobacillus was demonstrated in only 5 patients. CONCLUSIONS: development of CP is linked to persistent excessive cytokine response of Th17 cells, the intensity of which may affect clinical course of the disease; in parallel, H(2)O(2)-producing oral lactobacilli may prevent against progression of CP, most probably reducing secretory activity of Th17 cells and restricting growth of periodontopathogens. PMID- 22314573 TI - Protective effect of quercetin against sodium fluoride induced oxidative stress in rat's heart. AB - The antioxidative and cardioprotective properties of quercetin were investigated against sodium fluoride (NaF) induced oxidative stress in rat hearts. Experimental rats were divided into five groups. The first group served as the untreated (normal) control. The second group received NaF at a dose of 600 ppm through drinking water for 1 week, and served as the toxin control. The third and fourth groups were exposed to quercetin (at the dose of 10 and 20 mg kg(-1) intraperitoneally (i.p.) for 1 week) prior to NaF intoxication, and the fifth group was treated with vitamin C at a dose of 10 mg kg(-1) i.p., for 1 week prior to NaF intoxication and served as the positive control in the study. The activities of various antioxidant enzymes, superoxide dismutase and catalase, level of reduced glutathione and lipid peroxidation end product were determined in the cardiac tissues of all the experimental animals. NaF intoxication significantly altered all the indices related to the pro-oxidant-antioxidant status of the heart; treatment with the active constituents prior to NaF administration, however, prevented these alterations. The combined results suggest that quercetin protects rat hearts from NaF-induced oxidative stress, probably via its antioxidant properties. PMID- 22314574 TI - Genomics of gene banks: A case study in rice. AB - Only a small fraction of the naturally occurring genetic diversity available in the world's germplasm repositories has been explored to date, but this is expected to change with the advent of affordable, high-throughput genotyping and sequencing technology. It is now possible to examine genome-wide patterns of natural variation and link sequence polymorphisms with downstream phenotypic consequences. In this paper, we discuss how dramatic changes in the cost and efficiency of sequencing and genotyping are revolutionizing the way gene bank scientists approach the responsibilities of their job. Sequencing technology provides a set of tools that can be used to enhance the quality, efficiency, and cost-effectiveness of gene bank operations, the depth of scientific knowledge of gene bank holdings, and the level of public interest in natural variation. As a result, gene banks have the chance to take on new life. Previously seen as "warehouses" where seeds were diligently maintained, but evolutionarily frozen in time, gene banks could transform into vibrant research centers that actively investigate the genetic potential of their holdings. In this paper, we will discuss how genotyping and sequencing can be integrated into the activities of a modern gene bank to revolutionize the way scientists document the genetic identity of their accessions; track seed lots, varieties, and alleles; identify duplicates; and rationalize active collections, and how the availability of genomics data are likely to motivate innovative collaborations with the larger research and breeding communities to engage in systematic and rigorous phenotyping and multilocation evaluation of the genetic resources in gene banks around the world. The objective is to understand and eventually predict how variation at the DNA level helps determine the phenotypic potential of an individual or population. Leadership and vision are needed to coordinate the characterization of collections and to integrate genotypic and phenotypic information in ways that will illuminate the value of these resources. Genotyping of collections represents a powerful starting point that will enable gene banks to become more effective as stewards of crop biodiversity. PMID- 22314575 TI - Brief report: impaired differentiation of vegetative/affective and intentional nonverbal vocalizations in a subject with Asperger syndrome (AS). AB - The Asperger syndrome (AS) includes impaired recognition of other people's mental states. Since language-based diagnostic procedures may be confounded by cognitive linguistic compensation strategies, nonverbal test materials were created, including human affective and vegetative sounds. Depending on video context, each sound could be interpreted either as direct expression of an agent's affective/vegetative state or as result of intentional-executive mental operations. "Situational relevance" and "intentionality" ratings by a group of twelve healthy subjects nicely differentiated between context types. By contrast, an AS subject showed a systematic over-interpretation of vegetative/affective signals in terms of planned activities. Such overestimation of intentional motivation, leading to impaired social cognition, might be due to the inability to utilize "affective resonance" mechanisms for the interpretation of an individual's internal state. PMID- 22314576 TI - Limited disease of extra-pulmonary small cell carcinoma. Impact of local treatment and nodal status, role of cranial irradiation. AB - PURPOSE: As extra-pulmonary small cell carcinoma (EPSCC) is a rare entity of tumors, the available treatment recommendations are mainly based on retrospective analyses and deduction from treatment of small cell lung cancer. The aim of this study was to provide a detailed analysis concerning prognostic factors and treatment modalities. PATIENTS AND METHODS: A total of 20 patients with limited disease (LD) of EPSCC treated at our institution from 1999-2009 were retrospectively analyzed. Data were gathered from chart review. Localization, lymph node involvement, as well as local and systemic treatment were documented and their impact on pattern of failure and survival times statistically evaluated. RESULTS: With a median follow-up of 21 months, the estimated median overall- and disease-free survival were 59 and 25 months, respectively. Local control was excellent with 100% at 2 years. Nodal involvement was observed in 74% (n = 14/19) of evaluable patients. However, outcome was not altered by this parameter. Local treatment consisted of surgery in 10 cases, radiotherapy in 7 cases, and a combination of both in 3 cases. Only 3 patients (15%) developed hematogenous central nervous system metastases, while none of the patients received prophylactic cranial irradiation. CONCLUSION: Nodal involvement did not worsen prognosis. Local control was excellent irrespective of local treatment modality and the leading cause of failure was distant metastasis. Therefore, systemic treatment should not be omitted. Prophylactic cranial irradiation might be dispensable but discussed for head and neck malignancies. PMID- 22314577 TI - Radiation-induced changes in breathing frequency and lung histology of C57BL/6J mice are time- and dose-dependent. AB - PURPOSE: Pneumonitis and fibrosis constitute serious adverse effects of radiotherapy in the thoracic region. In this study, time-course and dose dependence of clinically relevant parameters of radiation-induced lung injury in C57BL/6J mice were analyzed. A well-characterized disease model is necessary for the analysis of the cellular and molecular mechanisms using genetically modified mice. MATERIAL AND METHODS: C57BL/6J mice received single dose right hemithorax irradiation with 12.5 or 22.5 Gy. Body weight and breathing frequency were recorded as parameters for health impairment. Lung tissue was collected over 24 weeks for histological analysis. RESULTS: Hemithorax irradiation with 12.5 or 22.5 Gy induced biphasic breathing impairment with the first increase between days 7 and 70. Although breathing impairment was more pronounced in the 22.5 Gy group, it was accompanied in both dose groups by pneumonitis-associated histological changes. A second rise in breathing frequency ratios became visible starting on day 70 with a steady increase until day 210. Again, breathing was more strongly affected in the 22.5 Gy group. However, breathing impairment coincided only in the 22.5 Gy group with a significant increase in collagen deposition in the lung tissue by day 210. Tissue inflammation and fibrosis were observed in the irradiated and the shielded lungs, pointing toward involvement of systemic effects. CONCLUSION: Hemithorax irradiation induces time-dependent pneumonitis and fibrosis in C57BL/6J mice. While hemithorax irradiation with 12.5 Gy is sufficient to induce lung inflammation, it is below the threshold for collagen deposition and fibrosis development by day 210. PMID- 22314578 TI - Radiation-induced cranial neuropathy in patients with nasopharyngeal carcinoma. A follow-up study. AB - GOAL: The purpose of the current study was to investigate the long-term characteristics of radiation-induced cranial nerve injury in nasopharyngeal carcinoma (NPC) patients. PATIENTS AND METHODS: We studied cranial nerve palsy (CNP) in 328 NPC patients who received radiotherapy between 1994 and 2006. Follow up was 93.6% complete as of December 2009. A total of 72 patients with CNP were recruited for analysis (56 men and 16 women). Patients with evidence of residual or recurrent tumor accompanied by CNP were excluded. The characteristics of CNP and the relationship with the radiation fields as well as re-ratiotherapy were evaluated. RESULTS: After a mean follow-up of 11.2 years, 72 patients were found to have developed CNP. The latency of palsy ranged from 0.6-16.0 years. For the 67 patients with first course radiation, the glossopharyngeal and vagus nerves were the most vulnerable combination, occurring in 57 patients (85.1%). Patients with facial-cervical field radiation had a significantly longer latency comparing with that of patients with facial-cervical split fields (p = 0.021). In the first 5 years, 49.3% of patients developed CNP, while 40.3% presented CNP in the second 5-year period. In patients with first course radiation, 61 patients had more than one CNP. With regard to the 5 patients with re-radiation, most of them had multiple upper cranial nerve injuries. CONCLUSION: Radiation therapy of NPC patients may lead to cranial neuropathy. Patients with facial-cervical radiation fields had a longer latency for the manifestation of CNP compared with those patients who were treated with split fields. In patients with re-radiotherapy, the frequency of upper cranial nerve injury increased greatly. PMID- 22314582 TI - [Subjective evaluation of voice quality after surgical or radiation treatment of T1 glottic carcinoma.] PMID- 22314579 TI - Stereotactic LINAC radiosurgery for the treatment of brainstem cavernomas. AB - BACKGROUND: The management of deep-seated cerebral cavernous malformations (CCMs) is still controversial. Although surgery remains the treatment of choice in patients with recurrent hemorrhage, patients with CCMs located in the brainstem are in many cases not eligible for resection due to high procedure-related morbidity and mortality. We evaluated the long-term outcome of LINAC radiosurgery (LINAC-RS) for the treatment of brainstem CCMs. PATIENTS AND METHODS: Between December 1992 and March 2008, 14 patients (6 men, 8 women) harboring brainstem CCMs underwent LINAC-RS. Pretreatment neuroimaging showed no associated developmental venous angiomas (DVAs) in any of our patients. Prior to treatment, all patients suffered at least from one symptomatic hemorrhage (median 1.8, range 1-3). A median follow-up of 7.1 years (range 2.0-16.8 years) could be obtained in 12 patients. We applied a median tumor surface dose of 13.9 Gy (range 11-18 Gy; median tumor volume 1.6 ml, range 0.4-4.3 ml). RESULTS: Following LINAC-RS, neurological outcome improved in 4 (33.3%) and remained unchanged in 8 patients (66.7%). Rebleeding with subsequent transient neurological status deterioration occurred in 4 patients (33.3%), leading to additional surgical resection in 2 patients (16.7%). The corresponding annual hemorrhage rate was 4.8% (4/82.8 patient-years). Adverse radiation effects (ARE, defined by perilesional hyperintensity on T2-weighted MR images) were revealed in 3 patients (25%), leading to transient neurological deficits in 2 patients (16.7%). There were no procedure-related complications leading to either permanent morbidity or mortality. CONCLUSION: Our results support the role of LINAC-RS as an efficient and safe treatment to significantly reduce the annual hemorrhage rate in patients suffering from brainstem CCMs not eligible to microsurgery. Compared with radiosurgery for arteriovenous malformations (AVMs), the intervention-related morbidity is higher. PMID- 22314583 TI - Anomalous lobar pulmonary vein resembling pulmonary arteriovenous malformation. AB - We present a case report of a 72-year-old man with an anomalous lobar pulmonary vein which was initially misdiagnosed as a pulmonary arteriovenous malformation on chest computed tomography. This uncommon condition was correctly diagnosed during pulmonary angiography performed as workup for the computed tomography finding. In this report, we describe the imaging findings in this case and discuss congenital anomalies of the pulmonary veins. PMID- 22314584 TI - Posttraumatic anomalous pulmonary edema. AB - Focal pulmonary edema from increased venous hydrostatic pressure is most commonly seen in mitral valve regurgitation (in the right upper lobe) or in pulmonary venous obstruction/compression from neoplastic, fibrotic, or iatrogenic causes (in any lobe). We describe a case of focal pulmonary edema of the left upper lobe in a patient with partial anomalous pulmonary venous return of the left superior pulmonary vein, where the draining left brachiocephalic vein was compressed by a subluxed sternoclavicular joint after trauma. In this case, recognition of the focal edema and anomalous pulmonary vein allowed for a diagnosis of clavicular subluxation. PMID- 22314585 TI - High serum immunoglobulin G4-related retrosternal fibrosclerosis. AB - A 65-year-old man with a history of exposure to asbestos complained of left leg edema. Computed tomography showed a flat, symmetrical, and longitudinal retrosternal thickening in addition to a presacral tumor. Retroperitoneal fibrosis was suspected. Serum immunoglobulin G4 (IgG4) levels were elevated (213 mg/dL). Thoracoscopic biopsy was performed. Histopathologic findings showed fibrotic tissue accompanied by proliferation of IgG4-positive plasma cells (proportion of IgG4/IgG-positive plasma cells >=70%) indicative of multifocal fibrosclerosis. PMID- 22314586 TI - Influence of polystyrenesulfonate on electron transfer quenching of ruthenium trisbipyridine luminescence by viologens: non-covalent assembly and covalent tethering of the ruthenium complex. AB - A new copolymer (RuB-PSS) of ruthenium(II)bis-(2,2'-bipyridine)(4-vinyl 2,2' bipyridine) and styrene sulfonate was prepared which tethers the ruthenium chromophore directly to the polymer backbone. The photophysical properties of the copolymer, and its luminescence quenching by viologens, were compared with those of ruthenium(II)tris-bipyridine, [Ru(bpy)(3)](2+), bound non-covalently to polystyrenesulfonate (PSS) via hydrophobic and electrostatic interactions. Enhancement of ruthenium polypyridyl complex luminescence in both systems is due to decreased rates of non-radiative decay when removed from bulk water as well as reduced oxygen quenching. Molecular dynamics simulations show an open PSS chain conformation with induction of local curvature around the ruthenium centres. Hence, the complexes remain exposed to water, albeit less so than in bulk solution, as evidenced by low enhancement of bound [Ru(phen)(2)dppz](2+) emission. Quenching by O(2) is hindered for both systems due to combined polarity, ionic strength, and viscosimetric effects that influence local concentrations and diffusion of reactants. Electron transfer quenching of the Ru centre by zwitterionic propyl viologen sulfonate (PVS(0)) and cationic methyl viologen (MV(2+)) is enhanced for [Ru(bpy)(3)](2+)/PSS, but retarded for RuB-PSS, despite the attraction of the quenchers for PSS. PSS binding hinders separation of the electron transfer products relative to aqueous solution, excepting an increase for RuB-PSS/PVS(0). We conclude that anionic hydrophobic polymers such as PSS can differentially influence forward- and reverse- electron transfer reactions depending on the charge and hydrophobicity of the reactants. In the context of small molecule binding, we find that PSS provides a tenable model for DNA. PMID- 22314587 TI - Correlation of surface-enhanced Raman spectroscopy and laser desorption ionization mass spectrometry acquired from silver nanoparticle substrates. AB - Applying complementary experiments, like laser desorption-ionization mass spectrometry (LDI-MS) and confocal surface-enhanced Raman microscopy, to the same physical sample location has the potential to elucidate the behavior of complex chemical and biochemical systems in ways that are not available to either method applied in isolation. In these experiments surface-enhanced Raman scattering (SERS) and LDI-MS are applied to the same sample spot using a common structure, deposited Ag colloids, both as ionization matrix and simultaneously as enhancing media for surface-enhanced Raman scattering of small organic molecules, dyes and lipids, and the behavior is compared. Three compounds-p-aminothiophenol (ATP), rhodamine 6G and cholesterol-which exhibit different strengths of interaction with Ag are examined in detail by correlated SERS and LDI-MS. The related mechanisms of nanoparticle-assisted desorption-ionization and Raman enhancement are explored by correlating mass and Raman spectra. The correlated spectra highlight the manner in which the different test compounds interact with plasmonic metal nanostructures. These coupled studies yield new insight into the transition of analyte from the metal-solution interface to gaseous ions, including, in the case of organothiols, a rich set of mixed clusters that provide chemical insight into the ion formation process. PMID- 22314588 TI - A novel dodine-free selective medium based on the use of cetyl trimethyl ammonium bromide (CTAB) to isolate Beauveria bassiana, Metarhizium anisopliae sensu lato and Paecilomyces lilacinus from soil. AB - This study evaluated the quaternary ammonium compound cetyl trimethyl ammonium bromide (CTAB) as an alternative to the chemically related dodecylguanidine (dodine) for the selective isolation of entomopathogenic fungi. Oatmeal agar (OA) with chloramphenicol was used as basal medium, and three concentrations of CTAB (0.5, 0.6, 0.7 g/L) were evaluated and compared against OA + 0.46 g/L dodine. Selective isolation and growth studies were performed with the entomopathogens Beauveria bassiana, Metarhizium anisopliae s.l. and Paecilomyces lilacinus and five common non-entomopathogenic non-target species. The three entomopathogenic fungi sporulated earlier on OA + 0.6 g/L CTAB than on OA + 0.46 g/L dodine, while none of the non-target fungi sporulated on OA + 0.6 g/L CTAB. All entomopathogenic fungal isolates grew on OA + 0.6 g/L CTAB, despite some intra species variation, whereas non-target fungi showed no growth or sporulation. OA + 0.6 g/L CTAB resulted in an efficient medium to isolate B. bassiana, M. anisopliae s. l. and P. lilacinus from soil samples. Results of our study suggest that OA + 0.6 g/L CTAB is a suitable, simple and inexpensive to prepare medium to replace OA + 0.46 g/L dodine for the selective isolation of these fungi. PMID- 22314589 TI - Botrytis caroliniana, a new species isolated from blackberry in South Carolina. AB - Blackberry fruits symptomatic for gray mold were collected from three commercial blackberry fields in northwestern South Carolina. Single-spore isolates were generated and two distinct phenotypes were discovered in each location; one sporulated on PDA and one did not. One isolate of each phenotype and location (six isolates total) were selected for in depth molecular and morphological characterization. Glyceraldehyde-3-phosphate dehydrogenase (G3PDH), heat-shock protein 60 (HSP60) and DNA-dependent RNA polymerase subunit II (RPB2) coding sequence alignment revealed Botrytis cinerea as the sporulating phenotype and a new yet undescribed species as the non-sporulating phenotype. The new Botrytis sp., described herein as Botrytis caroliniana, was most closely related genetically to B. fabiopsis and B. galanthina, the causal agents of gray mold disease of broad bean and snowdrop, respectively. It produces smaller conidia than either B. fabiopsis or B. galanthina, and sequence analysis of genes encoding necrosis and ethylene-inducing proteins (NEPs) also indicated that the Botrytis isolates represent a separate and distinct species. The new species is pathogenic on blackberry fruits and broad bean leaves, which distinguishes it further from B. galanthina. The new species formed white to pale gray colonies with short, tufted aerial mycelium and produced black sclerotia on PDA at 20 C. To our knowledge this is only the third Botrytis species discovered to cause disease on blackberry in the United States. PMID- 22314590 TI - New and interesting penzigioid Xylaria species with small, soft stromata. AB - Six penzigioid Xylaria species that are characterized by small, discoid to pulvinate, soft stromata are included in this study. Xylaria albocinctoides, X. bicampaniformis and X. lechatii are described as new; Nummularia albocincta, Hypoxylon carabayense and H. discolor are moved to the genus Xylaria to form new combinations X. albocincta, X. carabayensis and X. discolor respectively. An identification key is provided for the major aggregates of Xylaria that harbor penzigioid species as well as the species of the X. frustulosa aggregate, to which the six studied penzigioid Xylaria species belong. PMID- 22314591 TI - Wood-inhabiting fungi in southern China 5. New species of Theleporus and Grammothele (Polyporales, Basidiomycota). AB - During the examination of specimens of Theleporus and Grammothele (Polyporales, Basidiomycota) from tropical China, three new species, Theleporus membranaceus, T. minisporus and Grammothele denticulata, were identified based on both morphological and phylogenetic analyses. They are described and illustrated. T. membranaceus is characterized by its extremely thin basidiocarps (0.12 mm), small pores (7-10 per mm) and ellipsoid to broadly ellipsoid basidiospores. T. minisporus has the smallest basidiospores among the species in the genus. Grammothele denticulata is distinguished in the genus by gray pores, continuous hymenia over dissepiment edge and cylindrical basidiospores with tapering apex. Two annotated identification keys are provided for species thus far accepted in Theleporus and Grammothele. The phylogenetic relationships of Theleporus and Grammothele were inferred based on nITS sequences and are briefly discussed. The molecular evidence showed that Theleporus and Grammothele belong to the core polyporoid clade. PMID- 22314592 TI - New species and new records of Crinipellis from tropical and subtropical forests of the east coast of Mexico. AB - Crinipellis brunneoaurantiaca, C. pallidibrunnea and C. rubella are described as new species and their taxonomic position is discussed. The two former were collected in subdeciduous tropical forest and the latter in the montane cloud forest, all from the east coast of Mexico (central Veracruz). Crinipellis podocarpi, C. pseudostipitaria var. mesites, C. setipes, recorded in montane cloud forest, and C. tucumanensis, collected in subdeciduous tropical forest, also are discussed. Detailed macro- and microscopic descriptions, illustrations of distinctive microscopic characters and plates are presented for each species. PMID- 22314593 TI - Comparison between Tuber gennadii and T. oligospermum lineages reveals the existence of the new species T. cistophilum (Tuberaceae, Pezizales). AB - New collections of T. gennadii, T. oligospermum and T. asa (Tuberaceae, Pezizales) from the Mediterranean basin were compared on the basis of morphology and DNA sequences. Phylogenetic inference based on the internal transcribed spacer region (ITS) and the 28S nuclear large ribosomal subunit (nrLSU) indicates that T. gennadii includes at least two lineages with characteristic morphological traits. T. gennadii s. str. has small subglobose ascomata with conspicuous glebal locules that form a continuous labyrinth when mature and has a prosenchymatic peridium. T. lacunosum has medium to large, deeply lobed ascomata with small to very small isolated locules when mature and has a pseudoparenchymatic peridium. Two major clades were identified within the T. oligospermum group. On the basis of morphological, ecological and biogeographical data, these are identified with the taxa T. oligospermum (= T. asa) and T. sphaerospermum. Tuber oligospermum forms small to medium globose or subglobose, whitish ascomata, with globose to broadly ellipsoidal ascospores and is found in alkaline, sandy soils. Tuber sphaerospermum forms medium to large, irregularly globose or deeply lobed, yellowish ascomata, with regularly globose ascospores and is found in acidic soils. Finally, a new truffle species with a prosenchymatic peridium and globose to ellipsoid reticulate spores, collected in acidic argillaceous soils of Spain under Cistus ladanifer is proposed here as the new species T. cistophilum. PMID- 22314594 TI - Caetea, a new genus of Pucciniales on Piptadenia (Fabaceae) from Brazil. AB - A new genus of rust fungi (Basidiomycota, Pucciniales), with species type Caetea itatiaiaensis, was collected on Piptadenia (Fabaceae) at the Parque Nacional do Itatiaia in the Serra da Mantiqueira, states of Rio de Janeiro and Minas Gerais, Brazil. This genus is delimited as (i) three-celled teliospores borne on a single pedicel each with a corresponding apical cell and (ii) apical cells giving rise to distally capitate cysts that overhang the teliospore cells. PMID- 22314595 TI - The phylogenetic position of Haasiella (Basidiomycota, Agaricomycetes) and the relationships between H. venustissima and H. splendidissima. AB - Based on a combined ITS-LSU rDNA analysis, the omphalinoid genus Haasiella is shown to be part of the Hygrophoroid clade and sister to Hygrophorus. H. venustissima and H. splendidissima are conspecific; H. splendidissima is the tetrasporic/clamped and heterothallic form of H. venustissima. PMID- 22314596 TI - Hot topics III. Preface. PMID- 22314598 TI - The oral thrombin inhibitor dabigatran: strengths and weaknesses. AB - Since the quest for a better replacement of warfarin started several decades ago and new compounds were brought forward to clinical trials, the concept of an ideal anticoagulant frequently became presented in lectures and articles. We have here reviewed strengths and weaknesses of the oral thrombin inhibitor dabigatran in terms of pharmacokinetics and clinical data. When strengths clearly exceed the weaknesses for any characteristic, the drug fits into the concept of an ideal anticoagulant in that domain. It is evident that dabigatran does not accomplish that concept for all characteristics but it reaches well above warfarin. We believe it is unlikely that any drug will fulfill all criteria for the ideal anticoagulant. Laboratory testing for dabigatran will not be discussed in any detail in this article, which is instead the focus of other articles from this issue of Seminars in Thrombosis & Hemostasis. PMID- 22314599 TI - Determination of dabigatran in human plasma samples. AB - The oral direct thrombin inhibitor dabigatran effectively prevents arterial and venous thromboembolism using fixed doses without the need for adjustment according to laboratory results. Dabigatran is eliminated from the circulation by ~80% through the kidneys. However, the in vitro anticoagulant effect of dabigatran may be necessary to determine in special patient populations such as in the elderly, for renal impairment, before operations, bleeding or thrombotic episodes, and to monitor self-compliance. Several clotting and thrombin-specific chromogenic substrate assays are available to analyze the biological activity of dabigatran. All of them are prolonged in the presence of dabigatran. This article reports the effects of dabigatran on clinical routine assays and the potential usefulness for determination in special risk groups of patients when overdose or lack of compliance are suspected. PMID- 22314600 TI - Active online assessment of patients using new oral anticoagulants: bleeding risk, compliance, and coagulation analysis. AB - Clinicians prescribing new oral anticoagulants (OACs; dabigatran, rivaroxaban, and apixaban) should be aware of the exclusion criteria related to bleeding risks defined in published clinical studies. At least a quarter of patients currently using warfarin have an exclusion criterion that may prevent easy transition to the new OACs. In the summary of product characteristics for dabigatran, as an example, the target populations appear generalized. Due to fixed dosing and predictable pharmacology, routine laboratory monitoring of new OACs is deemed unnecessary. Under special circumstances, however, understanding the extent of thrombin or factor (F) Xa inhibition may aid in evaluating compliance and handling emergency interventions, bleeding complications, or overdoses. Although commonly available global coagulation-time assessments (prothrombin time and activated partial thromboplastin time) are insensitive, they may assist clinical management by indicating a severe accumulation of OACs; moreover, a normal thrombin time (TT) excludes a thrombin-inhibitor effect. In particular circumstances, specific assays (diluted TT, Ecarin clotting time, anti-FIIa or anti-FXa activity) may quantify the anticoagulant effect, but therapeutic ranges for dose adjustment are not yet established. Laboratory results are also influenced by clinical situation: e.g. bleed (consumption of coagulation factors) versus postoperative state (activation of coagulation). Without specific antidotes and evidence-based treatment strategies, new OACs are clinically worrisome in patients with impaired renal or liver function. Postmarketing surveillance and recording of bleeding complications (ICD-10 D68.32) are therefore of major importance. PMID- 22314601 TI - Current and emerging therapeutics for heparin-induced thrombocytopenia. AB - Heparin-induced thrombocytopenia (HIT) is a prothrombotic complication of heparin therapy. Little more than a decade ago, no effective agents were available to treat this devastating and potentially fatal disease. Since that time, driven by an increased understanding of pathogenesis, the management of HIT has undergone a revolution. Several effective agents for the treatment and prevention of HIT associated thrombosis are now available. These drugs have transformed the natural history of the disease, dramatically reducing the incidence of thrombosis. Nevertheless, available therapies remain far from ideal. Anticoagulants currently approved for the treatment of HIT are expensive, complex to manage, and carry a substantial bleeding risk. Fortunately, a pipeline of agents await that hold the promise of greater safety, convenience, and cost-effectiveness. The objectives of this review are to discuss currently available drugs for the treatment of HIT, highlight the limitations of these agents, and examine future therapies. PMID- 22314602 TI - Generation and breakdown of soluble ultralarge von Willebrand factor multimers. AB - Ultralarge von Willebrand factor (ULVWF) multimeric strings are rapidly secreted by, and anchored to, stimulated endothelial cells (EC), and are hyperadhesive to platelets until cleavage by ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). In ADAMTS-13-deficient familial and autoantibody-mediated thrombotic thrombocytopenic purpura (TTP), there is severely restricted cleavage of EC-anchored ULVWF-platelet strings. The small amount of active enzyme released from their EC cleaves ULVWF strings minimally just above EC surfaces, thus generating soluble ULVWF multimers that are 2.5 to 50 times longer than plasma von Willebrand factor (VWF) forms. Soluble ULVWF multimers (detected in TTP and several other disorders) are also hyperadhesive to platelets and can cause excessive platelet adhesion/aggregation. Without exogenous chemicals or extreme shear stress, soluble ULVWF multimers cannot be cleaved by ADAMTS-13 but can be de-assembled (reduced) in vitro, by a free thiol containing molecule (>30 kD) present in the cryosupernatant fraction of plasma that is not ADAMTS-13, thrombospondin-1, albumin, cysteine, or glutathione. This reduction may prevent occlusion of the microvasculature by embolic soluble ULVWF multimers (+/- adherent/aggregated platelets). New inhibitors of platelet adhesion to EC-anchored ULVWF multimeric strings and soluble ULVWF include an aptamer, a nanobody, and N-acetylcysteine. PMID- 22314603 TI - Thrombotic microangiopathies, thrombotic thrombocytopenic purpura, and ADAMTS-13. AB - Thrombotic microangiopathy (TMA) is a term used to describe a group of disorders characterized by hemolytic anemia (with prominent red blood cell fragmentation), thrombocytopenia, and thrombosis in the microvasculature. It may be used when describing patients with thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome, atypical hemolytic uremic syndrome, as well as a myriad of other disorders in which the TMA may be secondary to another disease or disorder. While limited information exists as to the exact cause of microthrombosis in many TMA, recent advances have been made in the understanding of TTP and its pathophysiology. This progress can be attributed to discovery of the von Willebrand factor cleaving protease ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), whose absence in TTP has given the disorder a distinct molecular identity. The discovery of this metalloprotease has prompted a significant amount of research relating to its role in TTP as well as its general function in hemostasis. The exact mechanisms by which this metalloprotease achieves its role are slowly being understood and these now provide other avenues by which TMA may occur. PMID- 22314604 TI - New insights into von Willebrand disease and platelet function. AB - Regulation of binding between von Willebrand factor (VWF) and the platelet receptor glycoprotein (GP) Ibalpha is one of the key steps in controlling hemostasis and thrombosis. On vascular injury at sites of high shear rates, the GPIbalpha interaction with subendothelial-bound VWF will initiate the tethering of circulating platelets to the vessel wall. Tethered platelets subsequently roll on the damaged vessel wall, a process that is amplified by the activation of the platelet integrin alphaIotaIotabbeta3 (GPIIb/IIIa). The initial tethering to VWF is rapidly followed by platelet binding to collagen through specific receptors (GPVI and alpha2beta1), leading to firm adhesion, activation, and additional stable bonds mediated by alphaIotaIotabbeta3. The above described interactions can result in two distinct processes: physiological hemostasis and pathological thrombosis. Furthermore, VWF carries coagulation factor VIII, which is involved in thrombin formation that in addition to activating platelets, mediates fibrin formation and has several other actions. The importance of VWF in hemostasis is well known in patients suffering from von Willebrand disease (VWD) who present with a defect in both platelet plug and fibrin formation. Type 2B VWD is of special interest as it may provide further insight into the mechanism by which VWF promotes the adhesion of platelets to a thrombogenic surface under conditions of high shear stress. The variant phenotypic manifestations in patients affected with type 2B VWD, however, have raised the question of locus heterogeneity in VWD as a consequence of, for example, additional defects in receptor or signaling proteins mediating platelet adhesion and aggregation. Indeed, quite a few polymorphisms of platelet receptors have been associated with increased bleeding in VWD. However, many aspects of the disease remain to be elucidated. For instance, thrombin and platelet procoagulant activity may be important counterplayers to determine the severity of the bleeding complications associated with VWD. PMID- 22314605 TI - Role of molecular genetics in hemophilia: from diagnosis to therapy. AB - Despite significant advancements, state-of-the-art care remains inaccessible to patients with hemophilia, especially those from developing countries. Thus, innovative approaches in the management of this condition are needed to improve their quality of life. In this context, genetic studies in hemophilia have contributed to the better understanding of its biology, the detection of carriers, and prenatal diagnosis, and even fostering newer therapeutic strategies. This article reviews the applications of molecular genetics in hemophilia, in general, and how such techniques can be useful for optimizing patient care, in particular. PMID- 22314606 TI - Prophylaxis in children with hemophilia: evidence-based achievements, old and new challenges. AB - Recurrent joint bleeding leading to progressive musculoskeletal damage (hemophilic arthropathy), in spite of on-demand replacement with deficient factor concentrates, is the clinical hallmark of severe hemophilia A and B (i.e., the congenital deficiencies of coagulation factors VIII and IX with circulating levels <1 IU/dL). Fifty years of clinical experience, which began in Northern Europe and then initiated in other European countries and in North America, up to the recent randomized clinical trials, have provided definitive evidence that preventing bleeding from an early age through long-term regular prophylactic concentrate infusions limits the adverse clinical consequences of arthropathy and its complications in the quality of life of hemophilic children. Primary prophylaxis started after the first joint bleed and/or before the age of 2 is now the evidence-based, first-choice treatment in severe hemophilia. Interestingly, recent data also suggest a role for early prophylaxis in preventing inhibitor development, the most serious complication of hemophilia therapy. Secondary prophylaxis is aimed to avoid (or delay) the progression of arthropathy. The earlier the treatment is started, the better the outcomes in joint status and quality of life. Although prophylaxis has radically transformed the natural history of severe hemophilia, relevant barriers to its implementation and diffusion remain. Beyond the obvious economic constraints and problems with venous access and long-term adherence, uncertainties regarding the optimal prophylaxis regimen require further evaluation in prospective studies to optimize approaches based on definite outcome measures and cost-effectiveness/cost-utility analyses. Scientific evidence, current clinical strategies, and open issues of prophylaxis in children with hemophilia will be addressed in this review. PMID- 22314607 TI - Thrombin and cancer: from molecular basis to therapeutic implications. AB - The relationship between cancer and thrombosis has been recognized for nearly 150 years. Although the mechanisms underlying this association are not completely understood, there are increasing evidences suggesting a pivotal role of thrombin in cancer biology. This review will focus on the most important pathways by which thrombin may affect cancer growth and dissemination. In addition, the potential role of congenital (i.e., hemophilia) and pharmaceutical (i.e., antithrombotic agents) anticoagulation in cancer incidence and survival will be investigated through the analysis of the published experimental and clinical studies. PMID- 22314608 TI - Platelet-derived microvesicles: multitalented participants in intercellular communication. AB - Platelets can release a heterogeneous pool of vesicles which include plasma membrane-derived microparticles (PMPs) and multivesicular body-derived exosomes. As both vesicle types are generated upon activation and their distinction is complicated due to an overlap in their molecular properties and sizes, they are best discussed as an entity, the platelet-derived microvesicles (PMVs). PMPs can be formed through several induction pathways, which determine their different molecular profiles and facilitate tailor-made participation in intercellular communication. This dynamic variability may lie behind the multifaceted and sometimes very different observations of the PMPs in physiological and pathological settings. Currently, little is known of platelet-derived exosomes. In all, PMVs not only participate in several homeostatic multicellular processes, such as hemostasis, maintenance of vascular health, and immunity, but they also play a role in thrombotic and inflammatory diseases and cancer progression. In the past few years, the number of original articles and reviews on microvesicles has dramatically increased, but the data simultaneously raise further questions, the answers to which depend on forthcoming analytical improvements. In this article, the differential activation pathways and the molecular and functional properties of PMVs are reviewed in context with their sometimes paradoxical role in health and in disease. Also, the methodological issues of PMV detection and analysis are discussed in the light of recent advances within the field. PMID- 22314609 TI - Vitamin D, thrombosis, and hemostasis: more than skin deep. AB - Vitamin D(3) deficiency is a highly prevalent condition worldwide. Clinically, vitamin D(3) has a key role in calcium homeostasis and bone mineralization and has recently been implicated in the pathogenesis and/or progression of several acute and chronic illnesses, including cardiovascular disease (CVD). Accumulating evidence from observational, prospective studies suggests that low levels of serum 25-hydroxyvitamin D(3) are independently associated with an increased risk of CVD events and death. The molecular mechanisms of this association remain incompletely understood. A variety of biologically plausible mechanisms may mediate a cardiovascular role for the active metabolite of vitamin D(3). 1 alpha,25-dihydroxyvitamin D(3) regulates the renin-angiotensin system, suppresses proliferation of vascular cell smooth muscle, improves insulin resistance and endothelial cell-dependent vasodilation, inhibits myocardial cell hypertrophy, exerts anticoagulant and antifibrotic activity, and modulates macrophage activity and cytokine generation. Overall, the high prevalence of vitamin D(3) deficiency and the plausible biological mechanisms linking this to CVD risk suggest that the treatment of vitamin D(3) deficiency to prevent CVD is a promising field to explore. Large placebo-controlled randomized clinical trials are urgently needed to determine whether vitamin D supplementation could have any potential benefit in reducing future CVD events and mortality risk. PMID- 22314610 TI - Factor analysis of nineteen executive function tests in a healthy adult population. AB - Although there has been some progress in identifying the range of skills that comprise the executive neurocognitive system, their assessment has proved to be a challenge. Operationalization of executive functions (EFs) may be progressed by identifying the cognitive constructs that underlie EF test performance via principal components analysis. The underlying factor structure of 19 EF tests was examined in a non-clinical sample of 200 adults (mean age = 30.8 [18-64] years); the sample comprised 97 men. Findings revealed only weak correlations between various measures derived from the EF tests. Exploratory factor analysis revealed a model comprising six independent factors, consistent with previous reports, describing the functions of the EF system. The factors comprised: Prospective Working Memory, Set-Shifting and Interference Management, Task Analysis, Response Inhibition, Strategy Generation and Regulation, and Self-Monitoring and Set Maintenance. Results confirm the diverse and heterogeneous nature of EFs and caution against conceptualizations that underestimate its complexity. Furthermore, variability within the "normal" executive system is evident, and further research is required to understand executive functioning in healthy populations. PMID- 22314611 TI - Understanding living skills: first steps to evidence-based practice. Lessons learned from a practice-based journey in the Netherlands. AB - Living skills training is a commonly used but sparsely described and researched - occupational therapy - intervention for people with severe mental health problems. A service improvement project was established in a mental health organization in the Netherlands starting in 2006 to design more effective living skills training courses for individuals and groups. The steps of the evidence based practice process underpinned the project. Theoretical and empirical evidence was derived from an extensive literature review. This was supplemented by the preferences of clients and their families as an equally valued source of evidence as is the experience and knowledge of a range of mental health professionals. Information from these three sources provided building blocks for the development of living skills training, resulting in an individual process guideline and two group courses. Implications for practice is that living skills training needs to be part of multidisciplinary treatment and can be best provided in the client's natural context. Limitations of this study are the lack of an evaluation of both the group courses and of the individual process guideline, also due to the continuous implementation in an ever-changing context. There is further need for research into the clinical and cost effectiveness of living skills training, both for individuals and groups, to support evidence-based decision making and service planning. PMID- 22314612 TI - Regulation of cell proliferation through a KIT-mediated mechanism in benign prostatic hyperplasia. AB - BACKGROUND: We investigated the role of the KIT-mediated mechanism in benign prostatic hyperplasia (BPH), and discuss the pathophysiology of BPH and a candidate target of BPH medical therapy. METHODS: We performed RT-PCR, Western blotting, and immunohistochemistry to examine the expression of KIT in the prostate using a human prostate stromal cell line (PrSC) and human prostate. To investigate the pathophysiological function of KIT, the effects of KIT ligand, stem cell factor (SCF), and imatinib mesylate on cell proliferation were investigated using PrSC. Additionally, we compared the expression level and distribution of KIT in normal prostate and BPH of humans to clarify the contribution of KIT to the pathogenesis of BPH. RESULTS: KIT was expressed in PrSC and human prostate, indicating that these samples are suitable for examining the function of KIT. Immunohistochemical analysis demonstrated that KIT was localized in interstitial cells (ICs) of the stromal component in human prostate. Administration of imatinib mesylate dose-dependently inhibited cell proliferation of PrSC with downregulation of JAK2 and STAT1, which are the main pathways downstream of SCF/KIT signal. SCF promoted cell proliferation of PrSC with upregulation of JAK2 and STAT1. KIT expression and the number of KIT-positive ICs in BPH were found to be significantly larger than in normal prostate. CONCLUSIONS: This is the first report to suggest that KIT regulates cell proliferation in the prostate and plays a significant role in the pathophysiology of BPH. Our study may lead to a greater understanding of the mechanism of BPH and provide a therapeutic target. PMID- 22314613 TI - Visualization of Caenorhabditis elegans cuticular structures using the lipophilic vital dye DiI. AB - The cuticle of C. elegans is a highly resistant structure that surrounds the exterior of the animal(1-4). The cuticle not only protects the animal from the environment, but also determines body shape and plays a role in motility(4-6). Several layers secreted by epidermal cells comprise the cuticle, including an outermost lipid layer(7). Circumferential ridges in the cuticle called annuli pattern the length of the animal and are present during all stages of development(8). Alae are longitudinal ridges that are present during specific stages of development, including L1, dauer, and adult stages(2,9). Mutations in genes that affect cuticular collagen organization can alter cuticular structure and animal body morphology(5,6,10,11). While cuticular imaging using compound microscopy with DIC optics is possible, current methods that highlight cuticular structures include fluorescent transgene expression(12), antibody staining(13), and electron microscopy(1). Labeled wheat germ agglutinin (WGA) has also been used to visualize cuticular glycoproteins, but is limited in resolving finer cuticular structures(14). Staining of cuticular surface using fluorescent dye has been observed, but never characterized in detail(15). We present a method to visualize cuticle in live C. elegans using the red fluorescent lipophilic dye DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate), which is commonly used in C. elegans to visualize environmentally exposed neurons. This optimized protocol for DiI staining is a simple, robust method for high resolution fluorescent visualization of annuli, alae, vulva, male tail, and hermaphrodite tail spike in C. elegans. PMID- 22314614 TI - Levels and trends in cardiovascular risk factors and drug treatment in 4837 elderly Dutch myocardial infarction patients between 2002 and 2006. AB - BACKGROUND: It is important to gain insight into opportunities for secondary prevention of cardiovascular disease. Our aim was to investigate levels and trends in cardiovascular risk factors and drug treatment in Dutch post-myocardial infarction (MI) patients between 2002 and 2006 and to make comparisons with the EUROASPIRE surveys (1999-2007). METHODS: We analysed data from 4837 post-MI patients (aged 69 years, 78% men) from 32 Dutch hospitals, using baseline cross sectional data from the Alpha Omega Trial. RESULTS: Between 2002 and 2006, significant declines were found in the prevalence of smoking (23% to 16%, p < 0.001), hypercholesterolaemia (>=5 mmol/l; 54% to 27%, p < 0.0001) and hypertension (>=140/90 mmHg; 58% to 48%, p < 0.001). The prevalence of antithrombotic drugs was high (97%). The prevalence of lipid-modifying drugs and antihypertensives was high, and increased (74% to 90%, p < 0.0001 and 82% to 93%, p < 0.001, respectively). The prevalence of obesity (27%) was high in 2002 and decreased to 24% in 2006, albeit not significantly. Diabetes prevalence was high and increased between 2002 and 2006 (18% to 22%, p = 0.02). In comparison with EUROASPIRE patients, who were on average 8-10 years younger, our study in 2006 included patients with lower levels of obesity, hypertension, hypercholesterolaemia, diabetes and lower use of antiplatelets and beta-blockers, but similar levels of lipid-modifying drugs. CONCLUSIONS: This study showed that older Dutch post-MI patients were adequately treated with drugs, and that risk factors reached lower levels than in the younger EUROASPIRE patients. However, there is room for improvement in diet and lifestyle, given the high prevalence of smoking, obesity, and diabetes. PMID- 22314615 TI - Treatment of nonsmall cell lung cancer: overcoming the resistance to epidermal growth factor receptor inhibitors. AB - PURPOSE OF REVIEW: Testing for epidermal growth factor receptor (EGFR) mutations has become standard practice in treating patients with advanced nonsmall cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (TKIs) are being offered as first-line therapy in patients with EGFR activating mutations. These drugs offer an increased progression-free survival and response rate compared with standard chemotherapy in this setting; however, resistance invariably occurs. This review discusses the development of resistance to EGFR TKIs and the progress that is being made to better understand how to overcome this resistance. RECENT FINDINGS: Results from recently published articles dealing with resistance to EGFR TKIs are allowing for a better understanding of this mechanism. No one treatment allows for overcoming this resistance. Understanding this resistance will likely become an individualized patient/tumor approach. Selecting which drug or drugs that may be suitable can only be determined based on the molecular mechanism of resistance. SUMMARY: Progress is being made in our understanding of the multiple pathways of resistance. Using a tumor molecular signature at the time of progression can determine the best treatment option. PMID- 22314616 TI - Older age, poor performance status and major comorbidities: how to treat high risk patients with advanced nonsmall cell lung cancer. AB - PURPOSE OF REVIEW: Lung cancer is the leading cause of mortality in men and women, and the majority of patients with nonsmall cell lung cancer (NSCLC) are over 65 years of age. Treatment of elderly patients with NSCLC poses a significant therapeutic challenge owing to numerous pre-existing comorbidities, often-poor performance status and the increased risk of chemotherapy toxicities. RECENT FINDINGS: Single-agent chemotherapy is well tolerated, leads to an improvement in survival and quality of life outcomes and is favored by many clinicians in the treatment of elderly patients with NSCLC. Results from recent elderly specific randomized phase III trials and retrospective subgroup analyses of several trials have evaluated the use of combination chemotherapy in this difficult subgroup of patients, with encouraging results. SUMMARY: Elderly patients derive significant benefit from combination cytotoxic chemotherapy over single-agent chemotherapy. Therapeutic options for elderly patients include chemotherapy and/or targeted therapy, based on the individual tumor histology and molecular profile. As our population ages, it is critical we develop treatment strategies that are well tolerated , and which both minimize toxicity and maximize efficacy. PMID- 22314618 TI - Current world literature. PMID- 22314617 TI - Cancer stem cells: relevance to clinical transplantation. AB - PURPOSE OF REVIEW: Despite blood or marrow transplantation (BMT) being arguably the most active modality against hematologic malignancies, relapses remain the major reason for failure. Many cancers have now been shown to harbor cells that are phenotypically and biologically similar to normal cells with self-renewal capacity; these so-called cancer stem cells (CSCs) typically constitute only a small fraction of the total tumor burden, but are hypothesized to be responsible for relapse after conventional-dose therapy. Here, we review whether CSCs may have relevance to BMT. RECENT FINDINGS: CSCs appear to be relatively resistant to standard anticancer therapies in vitro. The often-dramatic responses induced by chemotherapy in most hematologic malignancies are likely a consequence of their impressive activity against the bulk tumor cells. Although the clinical importance of CSCs remains unproven, new evidence suggests that the limited durability of many of these responses reflect resistant CSCs. It is possible that CSCs are also relatively resistant to both high-dose myeloablative conditioning and allogeneic graft-versus-tumor effects. Data on the ability of most hematologic CSCs to circulate even early in the natural history of a malignancy also raises concerns about contamination of autografts contributing to relapse. SUMMARY: Emerging data for the first time suggest CSCs may be responsible for relapse, even after BMT. However, BMT may be a particularly compelling setting to test CSC-targeting strategies because it provides the most effective clinical debulking of hematologic malignancies, and because CSC-targeting strategies may also enhance allogeneic antitumor immunity. PMID- 22314620 TI - Overweight and obesity in military personnel: sociodemographic predictors. AB - In the United States, nationally representative civilian studies have shown that BMI is associated with select sociodemographic characteristics. Active-duty military personnel are not included in these surveys and the persistence of these associations in military personnel is unknown. Data from the worldwide, representative 2002 and 2005 Department of Defense (DoD) Surveys of Health Related Behaviors Among Active Duty Military Personnel were used to assess the prevalence of overweight and obesity and, the association of BMI with sociodemographic characteristics. The final response bases included 12,756 (2002) and 16,146 (2005) personnel. Results indicated that the combined prevalence of overweight and obesity in military personnel increased to an all-time high in 2005 (60.5%) with higher prevalence of obesity in 2005 compared to 2002 (12.9% vs. 8.7, respectively, P <= 0.01). Holding other variables constant, regression analysis indicated that women were significantly less likely than men to be overweight or obese in both survey years (P <= 0.0001), which is contrary to civilian data. Similar to civilian data, the prevalence of obesity was significantly associated with increased age, black or Hispanic/Latino race/ethnicity, and being married (P <= 0.01). US military personnel are not immune to the US obesity epidemic. Demographic characteristics associated with being overweight should be considered when developing military-sponsored weight management programs. PMID- 22314621 TI - Associations of physical activity and sitting time with the metabolic syndrome among Omani adults. AB - Most findings on associations of physical activity and sedentary behavior with the metabolic syndrome are from developed countries; thus, we examined these relationships in adults from Sur, Oman. The Sur Healthy Lifestyle Survey (n = 1,335) used the World Health Organization (WHO) Stepwise methodology to assess chronic disease risk factors. Odds ratios for the metabolic syndrome were estimated using logistic regression models for domains of physical activity (work, transport, and leisure) and sitting time, and adjusted for confounding variables. Compared to their counterparts doing the least physical activity, lower odds of the metabolic syndrome were observed among those with higher work activity (0.60; 95% confidence interval (CI): 0.45, 0.80) and transport activity (0.69; 95% CI: 0.47, 1.00), but not leisure activity (0.91; 95% CI: 0.64, 1.32). Odds of the metabolic syndrome were higher in those who sat for >= 6 h daily compared to <3 h daily (odds ratio = 1.60, 95% CI: 1.04, 2.44), but not after further adjustment for physical activity. This is the first evidence from the Arabian Gulf on associations of physical activity and sitting time with the metabolic syndrome and provides empirical evidence to inform national physical activity guidelines, policies and programs. PMID- 22314622 TI - BMI trajectories among the severely obese: results from an electronic medical record population. AB - Epidemiological studies have documented the growing prevalence of severe obesity during the past three decades. The primary goal of this study was to estimate the trajectory of BMI change over 5+ years in a cohort of subjects identified as severely obese (BMI >=35). We conducted a retrospective cohort study among adults enrolled in Group Health (GH) in Washington State. We tracked 11,735 subjects with at least one BMI measure of 35 or greater in the calendar year 2005 through April 2010. Population averaged BMI trajectories were estimated as a quadratic function of time using a marginal regression model, adjusting for gender and baseline BMI and age. For the average male in GH, the estimated BMI trajectory exhibited a slightly inverted U-shaped pattern and a 0.17 increase in BMI over the sample period. For the average female, the BMI trajectory was slightly U shaped with BMI decreasing 0.03 units over the sample period. We found a high degree of heterogeneity in the shape of estimated trajectories across baseline characteristics with larger 5-year BMI increases among younger subjects with a lower initial BMI. We conclude that BMI changes over 5 years among individuals classified as severely obese are generally small and consistent with studies documenting BMI changes for individuals in other lower BMI categories. Our results also suggest that once the 35 BMI threshold is reached, individuals will continue to remain severely obese, especially at younger ages. PMID- 22314623 TI - Low macrophage accumulation in skeletal muscle of obese type 2 diabetics and elderly subjects. AB - In addition to adipose tissue, recent studies suggest that skeletal muscle may also be a source of low-grade inflammation, particularly in inactive and/or overweight individuals. The aim of this study was to examine the presence of macrophages in skeletal muscle from obese subjects with type 2 diabetes (T2D) before and after a 9-month exercise program (vs. a non-exercising control group) (Study 1) and in young vs. elderly subjects (Study 2). In both studies, CD68(+) macrophages in vastus lateralis biopsies were determined by immunohistochemistry and inflammation gene expression measured. Macrophage content (%) was calculated by the number of macrophages per 100 muscle fibers. In Study 1, we found relatively low numbers (2-3%) of CD68(+) macrophages in skeletal muscle in obese T2D subjects (BMI = 37.3 +/- 5.2 kg/m(2)), which were unchanged after a 9-month exercise program (P = 0.42). Similarly, in Study 2 (BMI = 27.1 +/- 2.5 kg/m(2)), CD68(+) macrophages were relatively low in muscle (4-5%) and were not different between young and elderly individuals (P = 0.42). However, elderly subjects had twofold higher CD68 and CD206 gene expression (both P < 0.002) than young participants. In both studies, CD68(+) muscle macrophages were not associated with BMI. In conclusion, we found little evidence of macrophage accumulation in skeletal muscle in obese T2D subjects or in elderly individuals. A 9-month exercise program was not associated with a decrease in macrophage content. PMID- 22314624 TI - Role of CD95 in pulmonary inflammation and infection in cystic fibrosis. AB - Cystic fibrosis is caused by a defective expression of the cystic fibrosis transmembrane conductance regulator (Cftr) gene, which results in chronic pulmonary inflammation and infections. The pathophysiological mechanisms by which these changes are induced in the lungs of patients with cystic fibrosis require definition. This study found that Cftr deficiency in mice results in the upregulation and activation of CD95. CD95 activation is caused by increased ceramide concentrations in cystic fibrosis lungs, as revealed by genetic modifications that normalize pulmonary ceramide concentrations. The activation of CD95 in cystic fibrosis lungs further increases pulmonary ceramide levels and results in a vicious feedback cycle of CD95 activation and ceramide accumulation. Genetic studies reveal that CD95 is crucially involved in the induction of aseptic inflammation, an increase in the bronchial cell death rate, and an increased susceptibility to infection of Cftr-deficient mice. All of these pathologies are partially corrected by heterozygosity of CD95 in Cftr-deficient mice. These findings identify CD95 as an important regulator of lung functions in cystic fibrosis and suggest that CD95 may be a novel target for treating cystic fibrosis. PMID- 22314625 TI - Hydrogen sulfide: a gasotransmitter of clinical relevance. AB - Though the existence of hydrogen sulfide (H2S) in biological tissues has been known for over 300 years, it is the most recently appreciated of the gasotransmitters as a physiologic messenger molecule. The enzymes cystathionine gamma-lyase (CSE) and cystathionine beta-synthase (CBS) had long been speculated to generate H2S, and inhibitors of these enzymes had been employed to characterize influences of H2S in various organs. Definitive evidence that H2S is a physiologic regulator came with the development of mice with targeted deletion of CSE and CBS. Best characterized is the role of H2S, formed by CSE, as an endothelial derived relaxing factor that normally regulates blood pressure by acting through ATP-sensitive potassium channels. H2S participates in various phases of the inflammatory process, predominantly exerting anti-inflammatory actions. Currently, the most advanced efforts to develop therapeutic agents involve the combination of H2S donors with non-steroidal anti-inflammatory drugs (NSAIDs). The H2S releasing moiety provides cytoprotection to gastric mucosa normally adversely affected by NSAIDs while the combination of H2S and inhibition of prostaglandin synthesis may afford synergistic anti-inflammatory influences. PMID- 22314626 TI - Genetic variants implicated in telomere length associated with left ventricular function in patients with hypertension and cardiac organ damage. AB - Telomere length has emerged as a biological correlate for ageing, which in turn is a risk factor for the manifestation of cardiovascular diseases. This study investigated the relation between leucocyte telomere length (LTL) and its genetic background to cardiac structure and function in patients with arterial hypertension. We analysed a cohort of 1,106 treated hypertensive patients (83.3% males; mean age, 57.9 +/- 9.8 years) with an ejection fraction (EF) over 40% and documented cardiovascular disease or target organ damage. LTL and genotypes of single nucleotide polymorphisms (SNPs), previously implicated in LTL, were determined by real-time PCR. The mean left ventricular mass index (LVMI) and EF were 51.8 +/- 21.0 g/H2.7 and 61.1 +/- 9.6%, respectively. In multivariate adjusted analysis, a 1.5-fold LTL was positively related with a 2.2% increase of LVMI (CI = 0.1% to 4.2%, p = 0.044) and an absolute increase in EF of 0.6% (CI = 0.1% to 1.1%, p = 0.028). One SNP near TERC (rs16847897) showed a significant absolute difference in EF dependent on allele status (rs16847897, G allele 2.7%; CI = 0.7% to 4.6%; p raw = 0.008, p mt = 0.048, after adjustment for multiple testing). This applied also for two SNPs in BICD1 (rs2630578, C allele -1.8%; CI = -2.8% to -0.7%; p raw = 0.002, p mt = 0.018; rs1151026, G allele -1.9%, CI = 3.0% to -0.8%; p raw < 0.001, p mt = 0.002) with the extension that a frequent haplotype in BICD1 showed an absolute -1.8% (CI = -3.0% to -0.7%; p raw = 0.002, p mt = 0.008) lower EF compared with those lacking this haplotype. Our results point to a role of genetic variants recently implicated in LTL for left ventricular function in hypertensive patients. PMID- 22314628 TI - Enhancing the device performance of Sb2S3-sensitized heterojunction solar cells by embedding Au nanoparticles in the hole-conducting polymer layer. AB - Performance of Sb(2)S(3)-sensitized heterojunction solar cells is enhanced by embedding Au nanoparticles in the poly-3-hexylthiophene (P3HT) hole-conducting polymer layer. The improved charge transfer/transport at the Sb(2)S(3)/P3HT/Au interface by extended interface area of the P3HT/Au counter electrode and the re absorption of the backscattering light from the embedded Au nanoparticles enhanced the device performance: J(sc) 11.0 to 12.8 mA cm(-2), V(oc) 606 to 626 mV, fill factor (FF) 60.5 to 61.2%, and power conversion efficiency (eta) 4.0 to 4.9%. Simultaneous enhancement of V(oc), J(sc), and FF in Au nanoparticle embedded systems is mainly attributed to the improved charge collection efficiency and light harvesting efficiency of Sb(2)S(3) due to the improved charge transfer/transport in the Sb(2)S(3)/P3HT/Au interface. PMID- 22314629 TI - Foot reflexology can increase vagal modulation, decrease sympathetic modulation, and lower blood pressure in healthy subjects and patients with coronary artery disease. AB - OBJECTIVE: Complementary and alternative medicine (CAM) has long been used by people to postpone the aging process and to reverse disease progression. Reflexology is a CAM method that involves massage to reflex areas in the feet and hands. This study investigated the effect of foot reflexology (FR) on the autonomic nervous modulation in patients with coronary artery disease (CAD) by using heart rate variability analysis. STUDY METHODS: Seventeen people with angiographically patent coronary arteries and 20 patients with CAD scheduled for coronary artery bypass graft surgery were recruited as the control and CAD groups, respectively. The normalized high-frequency power (nHFP) was used as the index of vagal modulation and the normalized very low-frequency power (nVLFP) as the index of vagal withdrawal and renin-angiotensin modulation. RESULTS: In both control and CAD groups, the nHFP was increased significantly whereas the nVLFP was decreased significantly 30 and 60 minutes after FR, as compared with those before FR. The systolic, diastolic, mean arterial, and pulse pressures were significantly decreased after FR in both groups of participants. In the CAD group, the percentage change in heart rate 30 and 60 minutes after FR was smaller than that in the control, and the percentage change in nVLFP 60 minutes after FR was smaller than that in the control. In conclusion, a higher vagal modulation, lower sympathetic modulation, and lower blood pressure can be observed following 60 minutes of FR in both controls and CAD patients. The magnitude of change in the autonomic nervous modulation in CAD patients was slightly smaller than that in the controls. CONCLUSION: FR may be used as an efficient adjunct to the therapeutic regimen to increase the vagal modulation and decrease blood pressure in both healthy people and CAD patients. PMID- 22314630 TI - Effect of the combination of music and nature sounds on pain and anxiety in cardiac surgical patients: a randomized study. AB - BACKGROUND: Postoperative pain and anxiety are common in cardiac surgery patients. Studies have suggested that music can decrease anxiety in hospitalized patients. Primary Study Objective This study focused on the efficacy and feasibility of special music, which included nature sounds, for pain and anxiety. METHODS/DESIGN: In this randomized controlled trial, postoperative cardiovascular surgery patients were randomly assigned to a music group to receive 20 minutes of standard postoperative care and music twice daily on postoperative days 2 through 4 or to a control group to receive 20 minutes of standard care with a quiet resting period twice daily on postoperative days 2 through 4. SETTING: Cardiovascular surgical unit of Saint Marys Hospital, Rochester, Minnesota. PARTICIPANTS: One hundred patients completed the study (music group, n = 49; control group, n = 51). Intervention The music was delivered through CD players in the patients' rooms. PRIMARY OUTCOME MEASURES: Pain, anxiety, satisfaction, and relaxation were evaluated from visual analog scales. RESULTS: Data showed a significant decrease in mean (SD) pain scores after the second session of day 2 for the music group (change, ?1.4 [1.4]) compared with the control group (change, ?0.4 [1.4]) (P = .001). Mean relaxation scores improved more at the first session of day 2 for the music group (change, 1.9 [2.7]) compared with the control group (change, 0.3 [2.9]) (P = .03). The music group also showed lower anxiety and increased satisfaction overall, but these differences were not statistically significant. No major barriers to using the therapy were identified. CONCLUSION: Recorded music and nature sounds can be integrated into the postoperative care of cardiovascular surgery patients. The recordings may provide an additional means for addressing common symptoms of pain and anxiety while providing a means of relaxation for these patients. PMID- 22314631 TI - Clinical depression: an evidence-based integrative complementary medicine treatment model. AB - BACKGROUND: Clinical depression has a major impact on individuals and society, often presenting the clinician with a significant challenge. Recent evidence suggests that synthetic antidepressants- although effective in the treatment of severe depressed mood-may have only a weak effect against mild-moderate forms of depression. In such cases, nonpharmaceutical options may be indicated. Furthermore, research findings suggest that select natural products are effective adjuvants when combined with synthetic antidepressants. Research concerning the treatment of depression emphasizes individual monotherapies, which is often incongruent with clinical reality. In practice, clinicians often use a variety of interventions; however, this approach may not be systematic, and many interventions used may not be based on strong evidence. PRIMARY OBJECTIVE: This article proposes an evidence-based prescriptive clinical model based on the biopsychosocial model to treat unipolar depression. The "Antidepressant-Lifestyle Psychological-Social (ALPS) depression treatment model" integrates nonpharmacological interventions (such as complementary medicines, lifestyle advice, and psychosocial techniques) for use by clinicians. RESULTS: Initially a review of nonpharmacological mood-elevating interventions was undertaken. Evidentiary support was revealed for use of psychological techniques such as cognitive and behavioral medicine and interpersonal therapy, St John's wort, S adenosyl methionine, and aerobic and anaerobic exercise. There were inconsistent research findings for acupuncture, omega-3 fish oils, and L-tryptophan for depressed mood. From these evidencebased interventions an integrative model was formed. Clinical recommendations in addition to a practical stepped-care decision tree are outlined. CONCLUSION: The ALPS model has the potential to improve treatment outcomes and reduce relapse rates in clinical depression and warrants research using rigorous and appropriate methodology. PMID- 22314632 TI - Modifiable disease risk, readiness to change, and psychosocial functioning improve with integrative medicine immersion model. AB - BACKGROUND: Stroke, diabetes, and coronary heart disease (CHD) remain leading causes of death in the United States and are largely attributable to lifestyle behaviors. Integrative medicine can provide a supportive partnership that focuses on improving health by identifying and implementing lifestyle changes based upon personal values and goals. OBJECTIVE: This prospective observational study was designed to assess the effectiveness of an integrative medicine intervention on modifiable disease risk, patient activation, and psychosocial risk factors for stroke, diabetes, and CHD. DESIGN: Sixty-three adults participated in a 3-day comprehensive, multimodal health immersion program at Duke Integrative Medicine, Duke University Medical Center, Durham, North Carolina. Participants received follow-up education, physician support, and telephonic health coaching between the immersion program and the endpoint 7 to 9 months later. PRIMARY OUTCOME MEASURES: Psychosocial functioning, readiness to change health behaviors, and risk of developing diabetes, stroke, and CHD were assessed at baseline and endpoint. RESULTS: Although cardiac risk remained unchanged (P = .19) during the study period, risk of diabetes (P = .02) and stroke (P < .01) decreased significantly. Perceived stress remained unchanged, but improvements were seen in mood (P < .05) and relationship satisfaction (P < .004). Patients became more activated towards self-management of health (P <.001), endorsed greater readiness to change health behaviors (P <.01), and reported increased aerobic exercise (P <.001) and stretching (P = .006) following the intervention. CONCLUSION: An integrative health model can help patients become more engaged in self-management of health and support them in making and maintaining healthy lifestyle changes. These findings provide support for use of an integrative health model in adult disease risk reduction. PMID- 22314633 TI - Menopause-related symptoms: traditional Chinese medicine vs hormone therapy. AB - OBJECTIVE: To compare the therapeutic effect of Chinese herbal medicine (CHM), acupuncture, and hormone therapy on menopause- related symptoms of peri- and postmenopausal women. STUDY DESIGN: Fifty-seven Chinese women completed 2 months of treatment with either CHM (5 g twice daily, n = 22), acupuncture plus CHM (Kun Bao Wan) 5 g twice daily plus sessions of acupuncture, n = 20), or hormone therapy (n = 15). MAIN OUTCOME MEASURES: Kupperman index score, levels of follicle-stimulating hormone (FSH) and estradiol, and the number of symptoms before and after treatment were the main outcome measures. RESULTS: CHM, acupuncture plus CHM, and hormone therapy significantly decreased Kupperman score (P < .001 in each group) and number of symptoms (P < .05). The mean difference in Kupperman score between baseline and 2 months among the three groups was significantly varied (P = .02). The difference was only between acupuncture plus CHM and CHM with significantly better results by acupuncture plus CHM. Acupuncture plus CHM, as well as hormone therapy, significantly reduced the level of FSH (P < .05), but CHM alone didn't cause any significant decrease in FSH levels (P > .05). The mean difference in the level of FSH between baseline and 2 months among the three groups was significantly different (P = .02). This difference was only between CHM and hormone therapy with significantly better results by hormone therapy. The three treatments didn't make any significant increase in the level of E2 (P > .05). CONCLUSION: application of the combination of Chinese herbal medicine and acupuncture proved as effective as hormone therapy in the treatment of menopause-related symptoms, and it achieved better outcomes than herbal medicine alone. PMID- 22314634 TI - Eurythmy Therapy in anxiety. AB - Anxiety is a highly frequent condition; many patients seek complementary treatment. One of these is anthroposophic medicine (AM) using therapeutic approaches that are based on a distinct concept of the human organism, illness, and healing. AM is applied in anxiety; however, little is known about underlying therapeutic concepts, the effectiveness, and the modalities of clinical reasoning and judgment. Presented is a 21-year-old woman who had suffered from severe and increasing anxiety for 6 months, which had led to social isolation and complete sick leave from work. She had attended an AM health care center and counseling at a psychiatric hospital but had not improved significantly after 6 months. Eurythmy therapy (EYT) was then applied for 8 weeks. Within the AM pathophysiological context, the patient was diagnosed as having stress-induced anxiety based on a juvenile disturbance of the rhythmical system. Associated symptoms were specific anomalies in the patient's eurythmy movement pattern, a "breathed-in-upwards syndrome." In the EYT sessions, clear interconnections between EYT-exercises and symptom-relief were observable, paralleled by a substantial relief of the patient's anxiety. EYT might have some impact on anxiety syndrome and should be investigated in more detail. PMID- 22314635 TI - Epithelial cell guidance by self-generated EGF gradients. AB - Cancer epithelial cells often migrate away from the primary tumor to invade into the surrounding tissues. Their migration is commonly assumed to be directed by pre-existent spatial gradients of chemokines and growth factors in the target tissues. Unexpectedly however, we found that the guided migration of epithelial cells is possible in vitro in the absence of pre-existent chemical gradients. We observed that both normal and cancer epithelial cells can migrate persistently and reach the exit along the shortest path from microscopic mazes filled with uniform concentrations of media. Using microscale engineering techniques and biophysical models, we uncovered a self-guidance strategy during which epithelial cells generate their own guiding cues under conditions of biochemical confinement. The self-guidance strategy depends on the balance between three interdependent processes: epidermal growth factor (EGF) uptake by the cells (U), the restricted transport of EGF through the structured microenvironment (T), and cell chemotaxis toward the resultant EGF gradients (C). The UTC self-guidance strategy can be perturbed by inhibition of signalling through EGF-receptors and appears to be independent from chemokine signalling. Better understanding of the UTC self-guidance strategy could eventually help devise new ways for modulating epithelial cell migration and delaying cancer cell invasion or accelerating wound healing. PMID- 22314636 TI - Quantification strategies for elemental imaging of biological samples using laser ablation-inductively coupled plasma-mass spectrometry. AB - This review provides analysts with critical insights of current approaches for quantification by laser ablation-inductively coupled plasma-mass spectrometry in the field of elemental imaging. This encompasses both calibration strategies that have been used with success in imaging biological samples, as well as those with potential to improve analytical accuracy and precision if applied to imaging. Methods reviewed include the use of CRMs, laboratory prepared matrix matched standards, internal standardisation, online standard addition and a variety of novel approaches that makes elemental imaging accessible to a wider base of analysts. The importance of quantification and factors affecting its use in imaging will also be considered. PMID- 22314637 TI - The Genetic Information Nondiscrimination Act (GINA): public policy and medical practice in the age of personalized medicine. AB - Survey data suggest that many people fear genetic discrimination by health insurers or employers. In fact, such discrimination has not yet been a significant problem. This article examines the fear and reality of genetic discrimination in the United States, describes how Congress sought to prohibit such discrimination by passing the Genetic Information Nondiscrimination Act of 2008 (GINA), and explores the implications of GINA for general internists and their institutions. It concludes that medical providers and health care institutions must be familiar with the general intent and specific terms of GINA, and should continue to collect genetic information that can contribute to the high quality provision of medical treatment. Not doing so violates their medical mission and diminishes the quality of care patients deserve. PMID- 22314638 TI - Early postmenopausal women with cardiovascular risk factors improve microvascular dysfunction after acute estradiol administration. AB - OBJECTIVE: This study aimed to compare endothelial microcirculatory function in hypertensive and diabetic (HD) and healthy postmenopausal women before and after nasal application of 17beta-estradiol. METHODS: Seventy-one women aged 42 to 59 years within 10 years of menopause, divided into HD (n = 31) and similar-age healthy (n = 40) women were evaluated noninvasively through nailfold videocapillaroscopy before and 1 hour after estradiol, measuring basal (RBCV) and maximum (RBCVmax) red blood cell velocity after 1 minute of arterial occlusion, representing baseline and endothelial-mediated vasodilation, and time to reach RBCVmax (TRBCVmax), representing microvascular compliance/stiffness. RESULTS: Hot flashes did not differ from or affect microvascular results. Before estradiol, HD showed lower RBCV (1.495 +/- 0.20 vs 1.52 +/- 0.10 mm/s, P = 0.019), borderline lower RBCVmax (1.655 +/- 0.09 vs 1.706 +/- 0.10 mm/s, P = 0.054), and shorter TRBCVmax (7.94 +/- 1.44 vs 8.8 +/- 2.03 s, P = 0.011) compared with healthy women. After estradiol, RBCV and RBCVmax increased, and TRBCVmax decreased in both groups (P = 0.0001 for all). HD women showed a higher RBCV increment (14.6% +/- 2% vs 11.1 +/- 1.4%, P = 0.021) associated with a smaller TRBCVmax reduction (23.6% +/- 2% vs 31% +/- 2%, P = 0.045). Changes in RBCVmax did not differ between HD (11.6% +/- 1%) and healthy (8.3% +/- 1.3%, P = 0.1) women. RBCV, RBCVmax, and TRBCVmax absolute values after estradiol were similar between groups. Past oral contraceptive exposure (P = 0.035) and cigarette smoking (P = 0.047) influenced healthy women's microvascular responses to estradiol, whereas triglyceride levels impaired HD vasodilation (P = 0.028). CONCLUSIONS: Before estradiol, HD presented impaired microvascular dilation and compliance compared with control women of similar age. After estradiol, HD recovered microvascular endothelial-mediated dilation, reaching similar absolute values, but the smaller reduction in TRBCVmax suggests irreversible microvascular stiffness. PMID- 22314639 TI - Thalamocortical projections of the anterodorsal thalamic nucleus in the rabbit. AB - The anterior thalamic nuclei consist of the anterodorsal (AD), anteroventral, and anteromedial nuclei, each of which are highly differentiated and may contribute to different aspects of various cognitive and memory functions. In particular, the AD is unique in that it is implicated in learning at the earliest stage of discriminative avoidance conditioning in the rabbit. To better understand the functional roles played by the AD in memory and learning processes, we analyzed the organization of thalamocortical projections of the AD in the rabbit, using the anterograde tracer biotinylated dextran amine and the retrograde tracer cholera toxin subunit B. The data show that the AD provides strong projections to layers I and IV of area 30 and to layers I, III, IV, and VI of area 29 in the retrosplenial cortex, and to layers I and III-VI of the presubiculum. The projections to the retrosplenial cortex are organized such that the rostral and caudal AD, respectively, project to the caudal and rostral retrosplenial cortex. In contrast, the projections to the presubiculum are not organized topographically. Other minor projections were also observed in the parasubiculum and part of the medial entorhinal area. These results indicate that the AD provides strong projections to the retrosplenial cortex and presubiculum, suggesting that these projections constitute essential pathways to these cortical regions for transmitting mnemonic information, such as a novel conditioning stimulus during the initial stage of avoidance learning. PMID- 22314640 TI - Monitoring kinase and phosphatase activities through the cell cycle by ratiometric FRET. AB - Forster resonance energy transfer (FRET)-based reporters(1) allow the assessment of endogenous kinase and phosphatase activities in living cells. Such probes typically consist of variants of CFP and YFP, intervened by a phosphorylatable sequence and a phospho-binding domain. Upon phosphorylation, the probe changes conformation, which results in a change of the distance or orientation between CFP and YFP, leading to a change in FRET efficiency (Fig 1). Several probes have been published during the last decade, monitoring the activity balance of multiple kinases and phosphatases, including reporters of PKA(2), PKB(3), PKC(4), PKD(5), ERK(6), JNK(7), Cdk(18), Aurora B(9) and Plk1(9). Given the modular design, additional probes are likely to emerge in the near future(10). Progression through the cell cycle is affected by stress signaling pathways( 11). Notably, the cell cycle is regulated differently during unperturbed growth compared to when cells are recovering from stress(12).Time-lapse imaging of cells through the cell cycle therefore requires particular caution. This becomes a problem particularly when employing ratiometric imaging, since two images with a high signal to noise ratio are required to correctly interpret the results. Ratiometric FRET imaging of cell cycle dependent changes in kinase and phosphatase activities has predominately been restricted to sub-sections of the cell cycle(8,9,13,14). Here, we discuss a method to monitor FRET-based probes using ratiometric imaging throughout the human cell cycle. The method relies on equipment that is available to many researchers in life sciences and does not require expert knowledge of microscopy or image processing. PMID- 22314641 TI - Acupuncture as add-on treatment in the management of a patient with ecthyma gangrenosum. AB - Acupuncture is believed to have a positive effect on wound healing. A case is presented in which the healing of a leg ulcer which proved to be difficult to treat coincided with the added treatment modality of needling healthy tissue surrounding the lesion. It raises questions about the potential effect of local dry needling on tissue regeneration. PMID- 22314644 TI - [Symptom experience, causal attribution and adherence to therapeutic regimens: patients with hypertension]. AB - Symptoms are the most important factor leading patients to seek medical help from health professionals. However, symptoms not directly supported by physiological and pathological evidence are often classified as being of emotional or psychological origin. Symptoms reflect an individual's subjective experience of physical-psycho-social functions, perception or cognition. Prior to implementing symptom management strategies, nurses should clarify patient symptom experiences and the meaning of such to patients. Individuals naturally seek symptoms based on physician diagnoses. When experiencing uncomfortable physical symptoms, individuals seek to label symptoms and accept medical advice based on their personal illness perception. In light of such, non-adherence to treatment recommendations may reflect inconsistencies between medical advice and patient symptom or illness diagnosis perception. In this paper, the author addresses relationships among symptom experience, symptom/illness attributions and therapeutic regimen adherence. Results identify the significant role that symptom experience plays in adherence to therapeutic regimens in patients with hypertension and suggests recommended revisions to clinical education in order to reflect such. PMID- 22314645 TI - [Cancer patients adherence and symptom management: the influence of the patient physician relationship]. AB - Appropriate management of cancer symptoms positively influences quality of life. Inappropriate symptom management, disease recurrence, co-morbidity and death result from lack of medication adherence. Factors influencing adherence are multidimensional and include personal attributes, knowledge and beliefs regarding the disease and medication, self-efficacy and social support. The patient physician relationship is a significant factor of influence in patient medication adherence and ultimate positive outcomes. If patients are satisfied with the relationship, they are highly likely to comply with health provider advice. Improving patient-physician relationships can effectively promote patient medication adherence. In cancer pain management and adjuvant hormone therapy for breast cancer, regular follow-up examinations have a positive impact. The physician-patient relationship with regard to cancer patient satisfaction is a relatively new topic of discussion, and many implications are scarcely understood. However, the physician-patient relationship should not be ignored as a factor in cancer symptoms management, especially with regard to promoting compliance behavior. PMID- 22314646 TI - [Evidence-based management of acute asthma exacerbation in children]. AB - Asthma is a common chronic disease among children in Taiwan. Acute asthma exacerbation is a cause of strong concern for children and parents and represents a challenge for pediatric healthcare providers. This review summarizes the most up-to-date information on assessing and managing acute asthma exacerbations in children. The latest guidelines (National Asthma Education and Prevention Program, Expert Panel Report 3, 2007 and the Global Initiative for Asthma, 2010) recommend using sensitive instruments to assess asthma exacerbation severity and administering early treatment in order to avoid emergency outpatient visits and hospitalizations. SABA (short acting beta-agonist) in combination with systematic cortisone is the most widely prescribed pharmaceutical intervention for acute asthma management. Other pediatric asthma medications are still in the trial stage. Educating parents on self-management techniques, especially with regard to the correct application of asthma medication on children, is crucial to reducing relapse incidents and visits to the emergency ward. Nursing studies addressing the issue of asthma exacerbation in children and parents are currently at the initial, qualitative stage. More evidence-based studies are necessary to explore and understand the independent role and function of nurses in acute pediatric asthma care. PMID- 22314647 TI - [Nursing assessment and management of patients with cardiogenic pulmonary edema]. AB - Cardiogenic pulmonary edema (CPE) is a clinical health problem that induces impaired gas exchange, dyspnea and hypoxia. This serious condition results in acute respiratory failure and high mortality rate. This article suggests an effective approach to CPE patient clinical symptom assessment and management. In accordance with evidence-based methods, we searched Cochrane, CINAHL and ScienceDirect and identified four Oxford Ia or Ib reports that employed a randomized controlled trial, systematic review and meta-analysis. Results suggest that prompt application of a non-invasive positive ventilator, especially continuous positive or bi-level positive airway pressure, can help patients reduce intubation risks, ICU stay days, and mortality rates. The authors hope to see more clinical trials on this topic to support evidence-based clinical nursing care. PMID- 22314648 TI - [Correlations among disease perceptions, attitudes and self-care behaviors in patients with interstitial cystitis]. AB - BACKGROUND: Interstitial cystitis (IC) is an enigmatic disease that currently remains incurable. Failure to adopt positive self-care behaviors can exacerbate recurrent clinical symptoms and significantly affect a patient's capacity to function normally in work, family and social setting. Proper disease perception can improve patient attitudes toward disease management and positively influence behavior. PURPOSE: This study investigated correlations between disease perceptions, attitudes and self-care behaviors in patients with interstitial cystitis. METHODS: This study used a cross-sectional method and enrolled 82 outpatients currently receiving treatment for interstitial cystitis at a medical center in East Taiwan. A structured questionnaires filled out individually and submitted by mail was used for date collection. RESULTS: (1) The mean perception scale score was 7.6, with 63.3% providing correct responses. (2) The mean attitude score of 3.5 indicated respondents held positive attitudes. (3) The mean self-care behavior score of 3.4 indicated a leaning toward "occasional" self-care behavior. (4) Correlations among disease perception, attitude and self-care behavior in participants exhibited a significant, mild and positive correlation. (5) Higher education level correlated positively with insight and attitude toward interstitial cystitis. Participants with lower "current voiding problems" had a more positive attitude toward their disease. Participants with higher "numbers of painful sites" had better disease perception and better self care behaviors. Patients reporting "symptoms aggravated by other conditions" also had better interstitial cystitis perception. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: We found positive correlations among disease perceptions, attitudes and self-care behaviors in patients with interstitial cystitis. We strongly recommend that all healthcare providers evaluate patient disease perception extent. Nurses should provide patients with correct disease concepts, and encourage positive attitudes and self-caring behaviors toward interstitial cystitis. PMID- 22314649 TI - [Factors of influence on willingness to participate in the N3 nursing clinical ladder program]. AB - BACKGROUND: The professional nursing clinical ladder program can effectively enhance the professional morale of nursing staff and help retain the best senior nurses in clinical settings. Hence, it is important to explore factors that influence nurse staff intentions to participate in the clinical ladder. PURPOSE: This study examined factors that affect nurse staff intention to participate in the N3 nurse clinical ladder program. METHODS: We used a cross sectional study design and a structured questionnaire survey. We employed purposive sampling to recruit 389 nurse staffs qualified for promotion to the N3 level from a medical center in southern Taiwan. RESULTS: Findings showed: (1) Nearly two-thirds (233, 59.9%) of participants intended to participate in clinical ladder; (2) The factors of age, years of nursing experience, years in current position, project/research experience, promotion experience, and intention all significantly affected intent to participate in the ladder; (3) A significant difference between willingness to participate in the ladder program and each of the following variables--motivation, satisfaction, professional capacity, and sense of achievement; (4) Logistic regression analysis identified only motivation as a valid predictor of willingness to participate the ladder program (95% CI: 1.21-3.78). CONCLUSION/IMPLICATIONS FOR PRACTICE: Results provide a useful reference to nursing administrators for planning on-the-job training and increasing nurse staff participation in the ladder. The authors hope results can help promote better human resource management and achievements. PMID- 22314650 TI - [Relationships among clinical symptoms, bladder condition, and subjective perceptions in patients with interstitial cystitis/painful bladder syndrome]. AB - BACKGROUND: Interstitial cystitis (IC) is a silent challenge for patients. Various symptoms related to IC are causes of physical disability and mental distress. PURPOSE: This study investigated the relationships between clinical symptoms, bladder condition and patient perceptions. METHODS: This study enrolled 107 patients diagnosed with interstitial cystitis at a medical center in eastern Taiwan and employed a cross-sectional design. Patient medical charts were reviewed. Structural questionnaires were used to collect data. RESULTS: Participants with a high symptom problem index had poor bladder compliance, severe glomerulation and high visual analog scale (VAS) scores. There was a positive correlation between Hunner's ulcer and a high VAS score. Patients with severe lower urinary symptoms, low competency and severe glomerulation earned significantly higher patient perception of bladder condition scores. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study found significant correlations between clinical symptoms, bladder condition and patient perceptions. This study may help enhance nursing staff knowledge of IC clinical symptoms so that they may provide appropriate interventions and education to improve patient self-care abilities and life quality. PMID- 22314651 TI - [Factors influencing the quality of life of elderly living in a pre-fabricated housing complex in the Sichuan earthquake area]. AB - BACKGROUND: The 2008 Sichuan Earthquake caused great damage to the environment and property. In the aftermath, many citizens were relocated to live in newly constructed prefabricated (prefab) communities. PURPOSE: This paper explored the current quality of life (QOL) of elderly residents living in prefabricated communities in areas damaged by the Sichuan earthquake and identified factors of influence on QOL values. The ultimate objective was to provide evidence-based guidance for heath improvement measures. METHODS: The authors used the short form WHOQOL-BREF to assess the quality of life of 191 elderly residents of prefabricated communities in the Sichuan Province 2008 earthquake zone. A Student's t-test, variance analysis, and stepwise multivariate regression methods were used to test the impact of various factors on QOL. RESULTS: Results indicate the self-assessed QOL of participants as good, although scores in the physical (average 56.2) and psychological (average 45.7) domains were significantly lower than the norm in China. Marital status, capital loss in the earthquake, number of children, level of perceived stress, income, interest, and family harmony each correlated with at least one of the short form WHOQOL-BREF domains in t-test and one-way analyses. After excluding for factor interaction effects using multivariate regression, we found interest, family harmony, monthly income and stress to be significant predictors of physical domain QOL, explaining 13.8% of total variance. Family harmony and interest explained 15.3% of total variance for psychological domain QOL; stress, marital status, family harmony, capital loss in the earthquake, number of children and interest explained 19.5% of total variance for social domain QOL; and stress, family harmony and interest explained 16.5% of total variance for environmental domain QOL. Family harmony and interest were significant factors across all domains, while others influenced a smaller proportion. CONCLUSIONS: Quality of life for elderly living in prefab communities should be improved. The authors hope study findings will increase awareness among healthcare providers regarding the quality of life of this vulnerable population. Study results suggest that key steps to promoting QOL in this population include improving family harmony, helping to cultivate well-rounded interests, alleviating economic stresses, providing necessary medical and psychological counseling services, and affording more social support. PMID- 22314652 TI - [Reflecting on nurse-patient relationships using core postmodernist concepts]. AB - The task of defining, maintaining, and mutually adapting the nurse-patient relationship has been ongoing since modern nursing's earliest days. The nurse patient relationship changes with social changes and paradigm shifts. Most medical centers today strive to incorporate the concept of partnership into the nurse-patient relationship in response to patient-centered medical care. What is the implication of this relationship? Is it suitable for all nurse-patient situations? What are the impacts on nurses and patients? How should nurses adapt to change in nurse-patient relationships? This article analyzes and reflects upon the nurse-patient relationship within a postmodernist framework guided by concepts of "deconstruction", "de-centralization", "multiplicity", and "inter subjectivity." We derive a "dual-active" and "dual-expert" partnership between nurses and patients that centers on patient disease management. Core values of this partnership are respect and caring, and strategies include emancipation, enlightenment, and empowerment. PMID- 22314653 TI - [Comfort: a concept analysis]. AB - Comfort is an important concept and core value of nursing. The defining attributes, antecedents and consequences of comfort need further analysis and exploration, even though the concept of comfort has been addressed previously in nursing literature. We employed the strategies of concept analysis as described by Walker&Avant (2005) to analyze the concept of comfort. The defining attributes of comfort include: 1) effective communication; 2) family and meaningful relationships; 3) maintaining functionality; 4) self-characteristics; 5) physical symptom relief, states, and interventions; 6) psychological, spiritual activities and states; and 7) a sense of safety and security. Antecedents consist of discomfort, distress and suffering. Consequences consist of (1) met/satisfied needs; (2) increased sense of control; (3) sense of inner peace; (4) a pleasant experience; (5) feeling cared for; (6) relief of symptoms; (7) reduced suffering; (8) decreased disequilibrium; and (9) absence of discomfort. We also outline the construction of cases, empirical references and comfort measurement tools. Analysis found comfort to have multiple dimensions and confirmed it as a clinical issue that should receive greater emphasis and valuation. Findings are hoped to increase nurse understanding of the concept of comfort and enable nurses to evaluate level of comfort and follow up on variations in such using empirical tools. Concept analysis can guide further comfort related interventions and research to benefit patients. PMID- 22314654 TI - [A "dialogue" between the aesthetics of nursing and philosophy]. AB - Nursing aesthetics belong to the broader school of aesthetics, a branch of philosophy, as well as the nursing arts, an element of professional nursing. The philosophy of aesthetics recognizes the connection between an author and appreciators and identifies both substantive and abstract aesthetic experiences in interpersonal communication through the fine arts. Nursing aesthetics values the meaningful moments of patients, is sensitive to the influences of different circumstances and situations, and appreciates the unique qualities of humanness. Nursing aesthetics is emancipatory knowledge and involves empirical, ethical and personal knowing. The article is based on a search of OvidSP and Chinese Electronic Periodical Services (CEPS) database references using key words including aesthetic, aesthetics, art of nursing, or nursing aesthetics as well as a review of books related to aesthetics, knowledge construction, and nursing aesthetics. Authors determined definitions as defined by nursing experts and the applications thereof in clinical practice. This article aimed to illustrate that the ultimate concern of philosophy is "goodness" and that the foundation of caring behaviors is "love". In practice, nursing aesthetics is expressed through empathy, appreciation, inspiration and the therapeutic use of the self. Through aesthetic knowing and enhanced perceptual sensibility and reflection, nurses can transform intuitive knowing into art-acts and ultimately enhance nursing care quality. PMID- 22314655 TI - [Introduction to grounded theory]. AB - Grounded theory, first developed by Glaser and Strauss in the 1960s, was introduced into nursing education as a distinct research methodology in the 1970s. The theory is grounded in a critique of the dominant contemporary approach to social inquiry, which imposed "enduring" theoretical propositions onto study data. Rather than starting from a set theoretical framework, grounded theory relies on researchers distinguishing meaningful constructs from generated data and then identifying an appropriate theory. Grounded theory is thus particularly useful in investigating complex issues and behaviours not previously addressed and concepts and relationships in particular populations or places that are still undeveloped or weakly connected. Grounded theory data analysis processes include open, axial and selective coding levels. The purpose of this article was to explore the grounded theory research process and provide an initial understanding of this methodology. PMID- 22314656 TI - [Nursing care of a school-age child with asthma: an ecological system theory approach]. AB - This research applied the Ecological System Theory of Dr. Bronfenbrenner (1979) to evaluate and analyze the impact of a school-age asthmatic child's ecological environment on the child's development. This project ran from March 16th to April 16th, 2010. A full range of data was collected during clinical care, outpatient follow-up services, telephone interviews, home visits, and school visits and then identified and analyzed. Results indicated that the family, household environment, campus, teachers, classmates, physical education program, and medical staffs comprised the most immediate microsystem and that parents, school nurses, teachers, and classmates formed the child's mesosystem. Researchers found a lack of understanding and appreciation in the mesosystem regarding asthmatic patient care needs. Hidden factors in the environment induced asthma, which eventually caused the child to be unable to obtain necessary medical care assistance. The exosystem reflected adequacy of the family social economy. The father's flexible working hours allowed him to allocate more time to childcare responsibilities. The government Asthma Medical Payment program also facilitated effective care. The macrosystem demonstrated parental cognition related to asthma treatment and caring to be deeply influenced by local customs. Thus, rather than using advanced medical treatments, parents preferred to follow traditional Chinese medicinal practices. Evaluation using the Ecological of Human Development Theory showed the subject's ecology environment relationships as based upon a foundation of family and school. Therefore, active family and school support for an asthma management plan appropriate to the subject's needs was critical. Asthma symptoms were better controlled after the child and his parents invested greater effort in mastering asthma management protocols. PMID- 22314657 TI - The equilibria and conversions between three excited states: the LE state and two charge transfer states, in twisted pyrene-substituted tridurylboranes. AB - Excited-state conversions were observed from a series of twisted pyrene substituted tridurylboranes, corresponding to a locally excited (LE) state, a more planar charge transfer (CT) state with a higher fluorescence quantum efficiency, and a more twisted CT state. PMID- 22314658 TI - Dielectric relaxation and ultrafast transient absorption spectroscopy of [C6mim]+[Tf2N]-/acetonitrile mixtures. AB - Mixtures of the ionic liquid (IL) [C(6)mim](+)[Tf(2)N](-) and acetonitrile have been investigated by a combination of dielectric relaxation spectroscopy (DRS) and ultrafast transient absorption techniques using the molecular probe 12'-apo beta-carotenoic-12'-acid (12'CA). Steady-state absorption spectra of the 12'CA molecule have also been recorded. The position of the probe's S(0)-> S(2) absorption maximum correlates linearly with the polarizability of the mixture, suggesting that the bulk composition is a good approximation to the local composition. The lifetime tau(1) of the S(1)/ICT state of 12'CA varies rather smoothly with composition between the value for pure acetonitrile (42 ps) and neat [C(6)mim](+)[Tf(2)N](-) (94 ps). At low IL contents there appears to be an influence of discrete ion pairs. Employing static dielectric constants from the DRS experiments, one finds that the lifetime of the probe in the IL mixtures is shorter than that in pure organic solvents with the same polarity parameter. This suggests an increased stabilization of the S(1)/ICT state in IL-containing mixtures, most likely due to IL-specific Coulombic interactions between the cation and the negative end of the probe's dipole. An ultrafast solvation component is observed which is ca. 0.5 ps in pure acetonitrile, and approaches the value for the pure IL (2.0 ps) already around x(IL) = 0.3. This is interpreted in terms of an efficient perturbation of the cooperative solvation response of acetonitrile by the presence of small amounts of IL and possibly also the viscosity increase when adding IL. This view is also supported by the increase of the average longitudinal relaxation time of acetonitrile upon addition of small IL amounts extracted from the DRS experiments. PMID- 22314659 TI - Regulatory T-cell subset analysis and profile of interleukin (IL)-10, IL-17 and interferon-gamma cytokine-producing cells in kidney allograft recipients with donor cells infusion. AB - BACKGROUND: This pilot study aimed to assess whether the perioperative infusion of donor bone marrow cells (DBMC) in renal allograft recipients can affect the appearance of peripheral regulatory T-cell subsets and the profile of cytokine producing cells [interferon-gamma (IFN-gamma), interleukin (IL)-17 and IL-10] 2 years after transplantation. METHODS: Fresh blood samples were collected from 14 kidney recipients who received infusion and from 13 kidney recipients without infusion who served as controls at the end of the second post-transplantation year. Initially the percentages of CD4(+)CD25(+)FoxP3(+) T cells and CD3(+)CD8(+)CD28(-) T cells were quantified using flowcytometry. Thereafter, the frequencies of IL-10-, IL-17- and IFN-gamma-producing cells were determined separately using the ELISPOT technique with peptides corresponding to mismatched donor HLA-DR molecules and phytohemagglutinin (PHA). RESULTS: The mean numbers of IFN-gamma- and IL-17-producing cells in response to PHA were lower in infused patients than in controls (P = 0.02 and P = 0.18, respectively); however, an increased frequency of IL-10-producing cells was observed compared to controls (P = 0.07). Furthermore, the ratio of IL-10/IFN-gamma-producing cells was significantly higher in the DBMC-infused group versus controls (P = 0.01). There was a negative correlation between the percentage of CD3(+)CD8(+)CD28(-)T cells and IL-17-producing cells in the infused group (r = -0.539, P = 0.04). The mean levels and the frequency of microchimerism within the first post-transplantation year were also significantly higher in infused patients than in controls (P = 0.007 and P = 0.001, respectively). CONCLUSION: Our findings suggest that DBMC infusion could partially stimulate the regulatory mechanisms against alloimmune responses in kidney allograft recipients PMID- 22314660 TI - AMIGO2 mRNA expression in hippocampal CA2 and CA3a. AB - AMIGO2, or amphoterin-induced gene and ORF (open reading frame) 2, belongs to the leucine-rich repeats and immunoglobulin superfamilies. The protein is a downstream target of calcium-dependent survival signals and, therefore, promotes neuronal survival. Here, we describe the mRNA distribution pattern of AMIGO2 throughout the mouse brain with special emphasis on the hippocampus. In the Ammon's horn, a detailed comparison between the subregional mRNA expression patterns of AMIGO2 and Pcp4 (Purkinje cell protein 4)--a known molecular marker of hippocampal CA2 (Cornu Ammonis 2)--revealed a prominent AMIGO2 mRNA expression level in both the CA2 and the CA3a (Cornu Ammonis 3a) subregion of the dorsal and ventral hippocampus. Since this CA2/CA3a region is particularly resistant to neuronal injury and neurotoxicity [Stanfield and Cowan (Brain Res 309(2):299-307 1984); Sloviter (J Comp Neurol 280(2):183-196 1989); Leranth and Ribak (Exp Brain Res 85(1):129-136 1991); Young and Dragunow (Exp Neurol 133(2):125-137 1995); Ochiishi et al. (Neurosci 93(3):955-967 1999)], we suggest that the expression pattern of AMIGO2 indeed fits with its involvement in neuroprotection. PMID- 22314661 TI - Early tissue transglutaminase-mediated response underlies K562(S)-cell gliadin dependent agglutination. AB - INTRODUCTION: [corrected] K562(S) agglutination has been used as a rapid and economic tool for the in vitro screening of the toxicity of cereal fractions and prolamins in celiac disease (CD). A strict correlation has been reported between the toxicity of cereals and cereal fractions for celiac patients and their ability to agglutinate K562(S) cells. Whether this specificity of K562(S)-cell agglutination is caused by the activation of the same pathogenic events triggered by toxic cereal fractions in CD intestine or simply represents a bystander event of gluten toxicity is, however, unknown. METHODS: K562(S) cells were incubated in vitro with the peptic-tryptic digest of wheat gliadin. RESULTS: The agglutination of K562(S) cells by wheat gliadin peptides is orchestrated by a cascade of very early events occurring at the K562(S)-cell surface similar to those occurring at the intestinal epithelial surface. They involve a rapid increase in intracellular calcium levels that activate tissue transglutaminase (TG2), leading to a rapid actin reorganization that is pivotal in driving cell agglutination. These specific effects of toxic cereals are phenocopied by the gliadin-derived peptide p31-43, which orchestrates the activation of innate response to gliadin in CD. DISCUSSION: Our study provides the rationale for the extensive use of K562(S) cell agglutination as a valuable tool for screening cereal toxicity. PMID- 22314662 TI - Dexamethasone and betamethasone protect against lipopolysaccharide-induced brain damage in neonatal rats. AB - INTRODUCTION: The aim of this study was to test whether dexamethasone (Dex) and betamethasone (Beta), two of the most commonly used corticosteroids, protect against lipopolysaccharide (LPS)-induced white matter damage and neurobehavioral dysfunction. METHODS: LPS or sterile saline was injected into the brain white matter of rat pups at postnatal day 5 (P5), and Dex or Beta was given intraperitoneally to the rat pups 1 h before the LPS microinjection. Brain inflammatory response, brain damage, and myelination were examined at P6, P8, and P14. Neurobehavioral tests were performed from P3 through P22. RESULTS: Our results demonstrate that Dex and Beta markedly diminish the LPS-induced brain inflammatory response, restore myelin basic protein (MBP) expression, and alleviate lateral ventricle dilation. Both corticosteroids demonstrate significant protection against most LPS-induced behavioral deficits, including those in rearing, vibrissa-elicited forelimb-placing, beam walking, learning, and elevated plus-maze test. Of note, only Beta improved the locomotion and stereotype dysfunction. In contrast to their beneficial effects, neither drug prevented LPS-induced delay in body weight gain from P6 through P21. DISCUSSION: Our study suggests that if their adverse effects are minimized, corticosteroids may be the potential candidate drugs to prevent brain damage in premature infants. PMID- 22314663 TI - Infection of pregnant mice with Listeria monocytogenes induces fetal bradycardia. AB - INTRODUCTION: Listeriosis is one of the most lethal bacterial diseases for fetuses and infants. However, pregnant women who get infected with Listeria may experience only mild symptoms, making the diagnosis difficult, even when the fetus is fatally infected. METHODS: To reveal features of this infection, we conducted a multimodality imaging study of Listeria-induced miscarriage, using a pregnant mouse model. In this model, fetal morbidity and mortality can be observed in utero, noninvasively, and the timing and extent of infection can be carefully controlled. By employing in vivo bioluminescence imaging (BLI), perinatal infections were localized over time such that a correlation of infection to outcome could be determined without the need to kill the animal subject. The morbidity and viability of fetuses were assessed with ultrasound, and fetal morphology was imaged using magnetic resonance imaging (MRI). RESULTS: The ultrasound revealed sustained fetal bradycardia, the slowing of the fetal heartbeat, in infected fetuses, with an association between slowed fetal heart rate and strong bioluminescent signal. DISCUSSION: Uninfected fetuses showing no bioluminescent signal in the same uterine horn exhibited normal heartbeats. Thus, fetal bradycardia during infection was localized to the infected fetus and was not systemic or disseminated. PMID- 22314664 TI - Systemic effects of whole-body cooling to 35 degrees C, 33.5 degrees C, and 30 degrees C in a piglet model of perinatal asphyxia: implications for therapeutic hypothermia. AB - INTRODUCTION: The precise temperature for optimal neuroprotection in infants with neonatal encephalopathy is unclear. Our aim was to assess systemic effects of whole-body cooling to 35 degrees C, 33.5 degrees C, and 30 degrees C in a piglet model of perinatal asphyxia. METHODS: Twenty-eight anesthetized male piglets aged <24 h underwent hypoxia-ischemia (HI) and were randomized to normothermia or cooling to rectal temperature (Trec) 35 degrees C, 33.5 degrees C, or 30 degrees C during 2-26 h after insult (n = 7 in each group). HR, MABP, and Trec were recorded continuously. RESULTS: Five animals cooled to 30 degrees C had fatal cardiac arrests. During 30 degrees C cooling, heart rate (HR) was lower vs. normothermia (P < 0.001). Although mean arterial blood pressure (MABP) did not vary between groups, more fluid boluses were needed at 30 degrees C than at normothermia (P < 0.02); dopamine use was higher at 30 degrees C than at normothermia or 35 degrees C (P = 0.005 and P = 0.02, respectively). Base deficit was increased at 30 degrees C at 12, 24, and 36 h vs. all other groups (P < 0.05), pH was acidotic at 36 h vs. normothermia (P = 0.04), and blood glucose was higher for the 30 degrees C group at 12 h vs. the normothermia and 35 degrees C groups (P < 0.05). Potassium was lower at 12 h in the 30 degrees C group vs. the 33.5 degrees C and 35 degrees C groups. There was no difference in cortisol level between groups. DISCUSSION: Cooling to 30 degrees C led to metabolic derangement and more cardiac arrests and deaths than cooling to 33.5 degrees C or 35 degrees C. Inadvertent overcooling should be avoided. PMID- 22314665 TI - Organizational justice and psychological distress among permanent and non permanent employees in Japan: a prospective cohort study. AB - BACKGROUND: Organizational justice has recently been introduced as a new concept as psychosocial determinants of employee health, and an increase in precarious employment is a challenging issue in occupational health. However, no study investigated the association of organizational justice with mental health among employees while taking into account employment contract. PURPOSE: The purpose of the present study was to investigate the prospective association of organizational justice (procedural justice and interactional justice) with psychological distress by employment contract among Japanese employees. METHODS: A total of 373 males and 644 females from five branches of a manufacturing company in Japan were surveyed. At baseline (August 2009), self-administered questionnaires, including the Organizational Justice Questionnaire (OJQ), the K6 scale (psychological distress scale), the Eysenck Personality Questionnaire Revised (EPQ-R), and other covariates, were used. After one-year follow-up (August 2010), the K6 scale was used again to assess psychological distress. Multiple logistic regression analyses were conducted by sex and employment contract. RESULTS: After adjusting for demographic characteristics, psychological distress, and neuroticism at baseline, low procedural justice was significantly associated with a higher risk of psychological distress at follow-up among non permanent female employees, while no significant association of procedural justice or interactional justice with psychological distress at follow-up was observed among permanent male or female employees. The results of non-permanent male employees could not be calculated because of small sample size. CONCLUSIONS: Low procedural justice may be an important predictor of psychological distress among non-permanent female employees. PMID- 22314666 TI - miR-141 modulates androgen receptor transcriptional activity in human prostate cancer cells through targeting the small heterodimer partner protein. AB - BACKGROUND: Aberrant expressions of microRNAs, including upregulation of miR-141, are closely associated with the tumorigenesis of prostate cancer (PCa). The orphan receptor small heterodimer partner (Shp) is a co-repressor to androgen receptor (AR) and represses AR-regulated transcriptional activity. METHODS: Here, we investigated the correlation of Shp expression with the cellular level of miR 141 and its effects on AR transcriptional activity in non-malignant and malignant human prostate epithelial cell lines. RESULTS: We found that Shp was downregulated in multiple PCa cell lines. The mature form of miR-141 was upregulated in PCa cells. miR-141 could target 3'-untranslated region of Shp mRNA resulting in translational suppression and RNA degradation. Moreover, enforced expression of Shp or inhibition of miR-141 function by anti-miR-141 attenuated AR regulated transcriptional activity in AR-responsive LNCaP cells. Phenethyl isothiocyanate, a natural constituent of many edible cruciferous vegetables, increased Shp expression, downregulated miR-141, and inhibited AR transcriptional activity in LNCaP cells. CONCLUSIONS: Shp is a target for miR-141 and it is downregulated in cultured human PCa cells with the involvement of upregulation of miR-141, which promotes AR transcriptional activity. Moreover, Shp and miR-141 could be targets for chemoprevention for PCa. PMID- 22314667 TI - Conspecific flowers of Sinapis arvensis are stronger competitors for pollinators than those of the invasive weed Bunias orientalis. AB - Biological invasions can affect the structure and function of ecosystems and threaten native plant species. Since most weeds rely on mutualistic relationships in their new environment, they may act as new competitors for pollinators. Pollinator competition is likely to be density dependent, but it is often difficult to disentangle competition caused by flower quality from effects caused by flower quantity. In order to test the effects of the presence and number of flowers of the invasive weed Bunias orientalis on the insect visitation rates in a native species (Sinapis arvensis), we performed two replacement experiments using plants with standardised flower numbers. The visitation rates in S. arvensis were significantly higher than in B. orientalis and the number of insect visits dropped significantly with increasing density of S. arvensis flowers. These results suggest that intraspecific competition among flowers of S. arvensis is stronger than the competitive effect of alien flowers. As flowers of B. orientalis do not seem to distract visitors from S. arvensis, it is unlikely that pollinator competition between these two plant species plays a crucial role. However, it cannot be excluded that mass blossom stands of B. orientalis may distract flower visitors from nativespecies. PMID- 22314668 TI - Can computer tomography help predict feasibility of transseptal puncture after percutaneous closure of an interatrial septal communication? AB - BACKGROUND: Transseptal puncture (TSP) is the first step in pulmonary vein isolation and catheter ablation, as well as in left atrial appendage closure in atrial fibrillation. Although TSP has been reported to be successful in patients with device closure of interatrial septal communications, questions pertinent to its feasibility in patients with large devices still remain. We sought to determine whether a "safe zone" for TSP could be visualised by computer tomography (CT), especially if larger device sizes for interatrial septal communication closure (IASC-C) had been used. METHODS: Retrospective observational study of 20 patients who underwent CT for de novo chest pain occurring after IASC-C or as a diagnostic test for suspected or proven coronary artery disease (CAD). Clinical follow-up was for 20.5 +/- 17.6 (6-84) months. CT was done 18 +/- 10 (2-28) weeks after IASC-C. Device size and dimensions of both atria in the long and short axes were measured, as was the minimal distance of the device edge to the inferior and inferoposterior atrial floor. RESULTS: The calculated minimal distance from the device edge to the inferior aspect (at 6 o'clock) of the (right or left) atrial floor was 7.2 +/- 6.5 (0-27) mm while that to the inferoposterior aspect (at 07:30 o'clock) was 5.3 +/- 4.2 (0-15) mm. In both locations, a distance of >6 mm was documented in ten patients (50%) while in nine patients (45%) a space of <6 mm was shown in both locations. There was no correlation between atrial dimensions or device size and minimal device distance to either wall. Conclusion With the exception of cases with the smallest devices (18 and 20 mm), neither device size nor atrial dimensions allow us to predict the feasibility of TSP in patients with a clamshell-type interatrial septal device in place, so that CT may be of help in determining whether a safe puncture space does exist in these patients. PMID- 22314669 TI - Natural history of the Sprint Fidelis lead: survival analysis from a large single center study. AB - PURPOSE: The purposes of our study were to: (1) determine lead failure rate in a large single-center cohort of Sprint Fidelis 6949 (Fidelis) leads, (2) define the risk of lead failure over time, (3) assess the impact of the Lead Integrity Alert (LIA) on lead failure presentation, and (4) identify independent predictors of Fidelis lead failure. METHODS: All patients who underwent implantation of a Fidelis lead between September 2004 and July 2007 were included. Demographic, clinical, and device characteristics at the time of implant and prior to failure were collected and analyzed. RESULTS: A total of 971 Fidelis leads (706 men, 265 women,mean age 68.4+/-12.8 years) were implanted. Over a mean follow-up of 46.3 months, there were 69 lead failures(7.1%). The 5-year lead survival rate was 90.3%. The risk of lead failure demonstrated a double-peaked pattern at 34 and 61 months. In multivariate analysis, there were no independent predictors of lead failure. Inappropriate shocks(IS) were the first sign of lead failure in 29 patients (42%).The incidence (32.6% vs. 65.2%, p=0.01) and number ofIS (2.8+/-7.2 vs. 11.3+/-18.7, p=0.01) were significantly lower in patients with LIA. CONCLUSIONS: This study presents a single-center experience on the natural history of the Fidelis lead. In our experience, lead survival declines at a lower rate when compared to prior reports. The risk of lead failure demonstrated a double peaked pattern at approximately 3 and 5 years. No identified variable was predictive of lead failure. LIA was effective in reducing the incidence and number of IS. PMID- 22314670 TI - Cardiac implantable electronic devices in end-stage renal disease patients: preservation of central venous circulation. PMID- 22314671 TI - Acute Effects of Acu-TENS on FEV1 and Blood Beta-endorphin Level in Chronic Obstructive Pulmonary Disease. AB - Background Pharmacotherapy is the mainstay of dyspnea management in patients with chronic obstructive pulmonary disease (COPD). Undesirable side effects have led to the application of alternative treatment strategies such as acupuncture. Our previous study showed that transcutaneous electrical nerve stimulation over acupuncture points (Acu-TENS), a noninvasive modality, can reduce dyspnea symptoms in patients with COPD, but the underlying mechanism is unknown. Primary Study Objective This study investigated the effect of acu-TENS on forced expiratory volume in one second (FEV1), dyspnea, and Beta-endorphin levels in patients with COPD. Design A double-blinded randomized controlled trial Setting: Hospital outpatient clinic Participants Forty-four subjects diagnosed with COPD Intervention Participants were randomly assigned to receive either acu-TENS or placebo-TENS on Dingchuan (EX-B1) for 45 minutes. Outcome Measures FEV1, forced vital capacity (FVC), dyspnea visual analogue score (DVAS), respiratory rate (RR), and blood Beta-endorphin levels were measured before and after therapeutic intervention. Results Our findings showed that the increase in FEV1 was 24.2% greater in the acu-TENS group than the placebo group (P < .0001). The decrease in RR and DVAS was also more in the acu-TENS group by 14.2% (P < .0001) and 20.7% (P = .006), respectively. The postintervention increase in Beta-endorphin was significantly higher in the acu-TENS than the placebo group (18.3%) (P = .027). Furthermore, the percentage reduction in RR correlated with the increase in Beta endorphin (R = -0.477, P = .033). Conclusion An improvement in FEV1 and dyspnea score at the end of Acu-TENS treatment was associated with a concurrent increase in b-endorphin level in patients with COPD. PMID- 22314672 TI - Determinants of meditation practice inventory: development, content validation, and initial psychometric testing. AB - Background Meditation health benefits have been difficult to document, as many efficacy studies are marred by lack of statistical power secondary to small sample size and/or threats to validity from high attrition. To date, no published studies have examined barriers to meditation that are likely responsible for low enrollment and high attrition. Objective To develop an instrument to capture barriers to meditation use, namely, the Determinants of Meditation Practice Inventory (DMPI). Design A five-step, mixed-methods approach was used, including literature review, qualitative interviews, content validation, reliability testing, and construct validation. Participants/Setting Four distinct participant groups contributed. Four meditation teachers participated in qualitative interviews. Five expert panelists conducted the content validation. Ten nonmeditators participated in the pilot test. For reliability testing and construct validation, 150 cancer family caregivers participated. Outcome Measures Big Five Inventory (BFI) and Caregiver Reactions Assessment (CRA) were used to test convergent construct validity. Results The three content domains are perceptions and misconceptions, pragmatic concerns, and sociocultural beliefs. Initially, 53 items were generated. Three reviews by the expert panel concluded with a 22-item survey. After pilot testing, a 17-item survey was created. Data from 150 caregivers showed Cronbach's coefficient alpha of 0.87. The intraclass correlation for baseline and retest was 0.86 (confidence interval 0.82-0.90). BFI and CRA were significantly and positively correlated with DMPI. Conclusion Preliminary results indicate the DMPI is psychometrically sound. By identifying barriers to meditation, the DMPI will enable researchers to address the needs and concerns of the target population when designing recruitment and intervention procedures, potentially maximizing recruitment, minimizing attrition, and optimizing interpretation of results. PMID- 22314673 TI - Three Cases of Chemotherapy-induced Peripheral Neuropathy Successfully Treated With Therapy Based on Kampo Diagnosis. AB - Patients undergoing chemotherapy often develop symptoms of neurological side effects such as numbness, pain, and weakness in a stocking-and-glove pattern. Yet few therapies are available to treat this condition. We examined the efficacy of therapy based on Kampo diagnosis in three cases of chemotherapy-induced peripheral neuropathy (CIPN). These patients all had severe cases, and the symptoms of CIPN interfered with their daily lives even after the cessation of the offending drugs. Early cessation of the drug therapy would be ideal, but in some cases where chemotherapies were effective against cancer, CIPN was worsened by prolonged administration. With the initiation of therapy based on Kampo diagnosis, the subjects of these case reports showed marked improvement in their daily activities. The Kampo diagnosis of CIPN is not only Jinkyo, as Tankaku, Kiutsu, and other Kampo clinical conditions can be candidates. We consider that the traditional way of Kampo diagnosis can provide options for the treatment of CIPN. PMID- 22314674 TI - A proposed conceptual model for studying the use of complementary and alternative medicine. AB - A conceptual model has the ability to combine theories, illustrate relationships, and describe behaviors. We propose a conceptual model to describe the interrelated factors that dictate and influence complementary and alternative medicine (CAM) use in the United States based on sociologic theories including Parson's Sick Role and Suchman's Stages of Illness as well as the Andersen Sociobehavioral Model of health services utilization. In our conceptual model, we distinguish CAM use by symptomatic vs asymptomatic individuals, practitioner based CAM services from products and self-administered CAM therapies, and the two ultimate endpoints: either the conclusion of CAM treatment or continuous CAM treatment. The development of our model underscores the importance of classifying CAM therapies based on the decision process of the CAM consumer rather than mechanism of action or CAM belief system in studying CAM health services utilization. PMID- 22314675 TI - An Examination of CAM Journals in the Journal Citation Reports. PMID- 22314676 TI - Haitian vodou as a health care system: between magic, religion, and medicine. AB - Haitian vodou has been considered an African-American religion organized around a pantheon, sanctuaries, priests, fraternities, and rituals honoring the spirits (lwa), the dead, and the ancestors. This construction of vodou, which is predominant in the literature, is based on a substantive approach to religion. It obscures the close connections between vodou and illness and does not adequately reveal how vodou is used in the daily lives of Haitians. By adopting a microsocial perspective on vodou and focusing on the knowledge and practices of vodou practitioners, the importance of vodou's therapeutic dimension becomes clear. Indeed, I am compelled to conclude that vodou is a health care system. Grounded in 16 months' research in the Haitian countryside and using a definition of health care systems identified in the medical anthropology literature, this new way of approaching vodou situates its religious and magical dimensions within its role as a health care system. This article deals with these different aspects, addressing the criteria that make vodou a health care system. In particular, I explore the practitioners who are recognized as healers and consulted as such; the sites where practitioners meet with the sick and treat them; the vodou theories on illness; and the curative, preventive, and care giving practices based on those theories. This approach helps us to better understand how medicine, religion, and magic are linked in Haitian vodou and leads us back to debates about the construction of vodou, which are apparently well known in the scientific literature. All of this leads us to reflect on Western approaches to healing and caring. PMID- 22314677 TI - Medicinal use of cannabis in Spain. PMID- 22314678 TI - Martha Stark, MD: "What Doesn't Kill You Makes You Stronger" Interview by Karen Burnett and Suzanne Snyder. PMID- 22314679 TI - Water-resistive humidity sensor prepared by printing process using polyelectrolyte ink derived from new monomer. AB - A simple strategy was developed based on a new monomer containing both photocurable function and ammonium salt, N-(2-cinnamoyloxy)ethyl-N-(2 (methacryloyloxy)ethyl)-N,N-dimethyl ammonium bromide (CMDAB) to obtain photocurable polyelectrolyte ink and stable humidity-sensitive membranes by printing process. Humidity-sensitive membranes are photocrosslinked polyelectrolytes obtained from copolymers of [2-(methacryloyloxy)ethyl] dimethyl propyl ammonium bromide (MEPAB), CMDAB and MMA. A flexible gold electrode/polyimide was pretreated with 2-(mercaptoethyl) cinnamamide (MEC) containing a thiol-coupling agent for the purpose of anchoring the humidity sensitive polyelectrolyte to the gold electrode. The sensors using screen printing methods reduced the deflection of sensor characteristics showing humidity precision +/-1%RH. The photocured copolymer MEPAB/CMDAB/MMA = 63/7/30 show good sensitivity (0.0586 logOmega/%RH) changing resistance approximately four orders of magnitude with relative humidity varying from 20% to 95% and fast response and recovery time. The resultant sensors showed acceptable linearity (Y = -0.04X + 7.0, R(2) = -0.9900) and small hysteresis. The reliability including water resistance and a long-term stability were estimated for the application of the flexible humidity sensor prepared by screen printing process. PMID- 22314680 TI - Land degradation at the Stara Planina ski resort. AB - The environmental impacts of ski resorts in the Balkan region are great and can lead to landscape degradation and loss of land functionality. In this study, we present an example of the negative effects of human activities at the Stara Planina ski resort in southeastern Serbia. The objective of this study is detailed analysis of the characteristics of environmental impacts at the Stara Planina. The management of the ski area and ski slope development caused severe degradation of topsoil and native vegetation. The morphological characteristics of the area, lithological properties of the exposed material and climate conditions resulted in various geomorphic impacts, including rills, deep gullies, solifluctions and debris from rock weathering. Significant changes in land usage altered hydrological conditions, resulting in more frequent torrential floods in the downstream sections of the Zubska River and increased the sediment yield. Environmental impacts were analyzed in the immediate and wider zones of the ski resort in accordance with the specific topography and visual exposure. The restoration and erosion control measures have stopped degradation processes and helped to rehabilitate the appearance and functions of the landscape. The results show the importance of considering lithological (the type and characteristics of minerals present) and hydrological (precipitation, water storage capacity of soil, runoff) factors under the conditions of significant changes in land usage. The results of this investigation can contribute to the improvement of planning processes and the implementation of development projects in ski areas. PMID- 22314681 TI - Reforestation strategies amid social instability: lessons from Afghanistan. AB - Foreign and domestic government agencies and other international organizations pursue reforestation programs in rural upper watershed areas of Afghanistan over the past decade to alleviate poverty, combat the insurgency and rehabilitate a depleted forest resource base. Popular programs incorporate cash-for-work to conduct hillside terracing, check dam construction and tree-planting for nut production, fuel wood, timber, dune stabilization, and erosion abatement. Programmatic approaches have varied as a function of accessibility, security and local objectives. Uncertain land tenure and use rights, weak local environmental management capacity, and a focus on agricultural production to meet immediate needs limit interest, nationally and locally. Unreliable security, a lack of high quality tree planting stock, limited technical knowledge and coordination among government agencies, and poor security hamper program expansion. Reforestation success would be most likely where these issues are least acute. The Afghan government should focus on supporting community based natural resource management, developing and disseminating improved conservation tree nursery strategies, and promoting watershed management schemes that incorporate forestry, range management and agronomic production. Reforestation practitioners could benefit from the human and material resources now present as part of the international war effort. Successes and failures encountered in Afghanistan should be considered in order to address similar problems in insecure regions elsewhere when reforestation may help reverse environmental degradation and contribute to broader social stabilization efforts. PMID- 22314682 TI - Synergistic toxicity of the environmental neurotoxins methylmercury and beta-N methylamino-L-alanine. AB - Determination of the environmental factors involved in neurodegenerative diseases has been elusive. Methylmercury and beta-N-methylamino-L-alanine (BMAA) have both been implicated in this role. Exposure of primary cortical cultures to these compounds independently induced concentration-dependent neurotoxicity. Importantly, concentrations of BMAA (10-100 MUM) that caused no toxicity alone potentiated methylmercury (3 MUM) toxicity. In addition, concentrations of BMAA and methylmercury that had no effect by themselves on the main cellular antioxidant glutathione together decreased glutathione levels. Furthermore, the combined toxicity of methylmercury and BMAA was attenuated by the cell permeant form of glutathione, glutathione monoethyl ester. The results indicate a synergistic toxic effect of the environmental neurotoxins BMAA and methylmercury, and that the interaction is at the level of glutathione depletion. PMID- 22314683 TI - Expression of equilibrative nucleoside transporter type 1 protein in elderly patients with schizophrenia. AB - Alterations in glutamatergic neurotransmission are thought to be involved in several psychiatric disorders, including schizophrenia. Equilibrative nucleoside transporter type 1 (ENT1) regulates glutamate levels by regulating excitatory amino acid transporter expression and activity in the brain. In this study, we investigated whether ENT1 is abnormally expressed in the brain of elderly patients with schizophrenia. We measured protein expression of ENT1 in the superior temporal gyrus (STG) and anterior cingulate cortex (ACC) in patients with schizophrenia (STG, n=22; ACC, n=34) and a comparison group (STG, n=24; ACC, n=29). We found decreased ENT1 expression in the STG in patients with schizophrenia, supporting the hypothesis of altered glutamate transport in this illness. PMID- 22314684 TI - Neural correlates of auditory distraction revealed in theta-band EEG. AB - Selective attention involves the exclusion of irrelevant information in order to optimize perception of a single source of sensory input; failure to do so often results in the familiar phenomenon of distraction. The term 'distraction' broadly refers to a perceptual phenomenon. In the present study we attempted to find the electrophysiological correlates of distraction using an auditory discrimination task. EEG and event-related potential responses to identical stimuli were compared under two levels of distraction (continuous broad-band noise or continuous speech). Relative to broad-band noise, the presence of a continuous speech signal in the unattended ear impaired task performance and also attenuated the N1 peak evoked by nontarget stimuli in the attended ear. As the magnitude of a peak in the event-related potential waveform can be modulated by differences in intertrial power but also by differences in the stability of EEG phase across trials, we sought to characterize the effect of distraction on intertrial power and intertrial phase locking around the latency of the N1. The presence of continuous speech resulted in a prominent reduction of theta EEG band intertrial phase locking around the latency of the N1. This suggests that distraction may act not only to disrupt a sensory gain mechanism but also to disrupt the temporal fidelity with which the brain responds to stimulus events. PMID- 22314685 TI - Neuronal to oligodendroglial alpha-synuclein redistribution in a double transgenic model of multiple system atrophy. AB - Multiple system atrophy is a sporadic, progressive, neurodegenerative disease characterized by an oligodendroglial accumulation of alpha-synuclein (alpha-syn). The mechanisms underlying the oligodendroglial accumulation of alpha-syn in the brains of patients with multiple system atrophy have attracted a great deal of interest, given the primarily neuronal role reported for this protein. We examined the interactions between neuronal and oligodendroglial alpha-syn in the progeny of crosses between parental transgenic (tg) mouse lines that express alpha-syn either under the oligodendroglial-specific myelin-basic protein promoter (MBP1-halpha-syn tg) or under the neuronal platelet-derived growth factor promoter (PDGF-halpha-syn tg). Our results demonstrate that progeny from the cross [halpha-syn double (dbl) tg mice] displayed a robust redistribution of alpha-syn accumulation, with a relocalization from a neuronal or a mixed neuronal/oligodendroglial alpha-syn expression to a more oligodendroglial pattern in both the neocortex and the basal ganglia that closely resembled the parental MBP-halpha-syn tg line. The halpha-syn dbl tg mice also displayed motor deficits, concomitant with reduced levels of tyrosine hydroxylase and augmented neuropathological alterations in the basal ganglia. These results suggest that the central nervous system milieu in the halpha-syn dbl tg mice favors an oligodendroglial accumulation of alpha-syn. This model represents an important tool to examine the interactions between neuronal and oligodendrocytic alpha-syn in diseases such as multiple system atrophy. PMID- 22314686 TI - Proteomic analysis of proteins associated with cellular senescence by calorie restriction in mesenchymal stem cells. AB - Mesenchymal stem cells (MSCs) hold great promise for use in cell-based therapies because of their multipotency and simple methods for in vitro expansion. However, during in vitro expansion, MSCs will age and lose their multipotency and proliferation capability. Previous studies have reported that calorie restriction (CR) increases proliferation of MSCs and decreases apoptosis. Therefore, in this study, we examined the effect of low glucose (LG) on human bone marrow-derived MSCs. Proliferation under low glucose (LG, 1.4 mM) conditions was compared with that under normal glucose (NG, 5.5 mM) conditions. In addition, comparative studies of population doubling (PD), beta-galactosidase (beta-GAL) activity, reactive oxygen species (ROS) generation and differentiation capacity (osteocytes and adipocytes) in NG and LG conditions were performed. In addition, protein expression patterns were compared between NG and LG conditions and several proteins were found to be up- or down-regulated under the glucose restriction condition (LG condition). As a result, CR does not seem to have a significant effect on proliferation, ROS generation, glucose consumption concentration, population doublings, and adipogenic differentiation of MSCs. Interestingly, however, the differentiation potential into osteocytes was maintained under CR and a lower senescence-associated beta-galactosidase (beta-GAL) activity was observed under CR than under the NG condition. In addition, we determined three up-regulated proteins (aldehyde dehydrogenase, neuropolyprptide h3, and prolyl 4 hydroxylase alpha subunit) and seven down-regulated proteins (laminin-binding protein, actin, sec 13 protein, alpha soluble N-ethylmaleimide-sensitive fusion protein (NSF)- attachment protein (SNAP), manganese superoxide dismutase, proteasome alpha 1 subunit, and ribosomal protein S12) via two-dimensional electrophoresis analysis. These results imply that differentially expressed proteins under the LG condition may provide further information on the aging and differentiation of stem cells. PMID- 22314687 TI - Tissue preparation and immunostaining of mouse sensory nerve fibers innervating skin and limb bones. AB - Detection and primary processing of physical, chemical and thermal sensory stimuli by peripheral sensory nerve fibers is key to sensory perception in animals and humans. These peripheral sensory nerve fibers express a plethora of receptors and ion channel proteins which detect and initiate specific sensory stimuli. Methods are available to characterize the electrical properties of peripheral sensory nerve fibers innervating the skin, which can also be utilized to identify the functional expression of specific ion channel proteins in these fibers. However, similar electrophysiological methods are not available (and are also difficult to develop) for the detection of the functional expression of receptors and ion channel proteins in peripheral sensory nerve fibers innervating other visceral organs, including the most challenging tissues such as bone. Moreover, such electrophysiological methods cannot be utilized to determine the expression of non-excitable proteins in peripheral sensory nerve fibers. Therefore, immunostaining of peripheral/visceral tissue samples for sensory nerve fivers provides the best possible way to determine the expression of specific proteins of interest in these nerve fibers. So far, most of the protein expression studies in sensory neurons have utilized immunostaining procedures in sensory ganglia, where the information is limited to the expression of specific proteins in the cell body of specific types or subsets of sensory neurons. Here we report detailed methods/protocols for the preparation of peripheral/visceral tissue samples for immunostaining of peripheral sensory nerve fibers. We specifically detail methods for the preparation of skin or plantar punch biopsy and bone (femur) sections from mice for immunostaining of peripheral sensory nerve fibers. These methods are not only key to the qualitative determination of protein expression in peripheral sensory neurons, but also provide a quantitative assay method for determining changes in protein expression levels in specific types or subsets of sensory fibers, as well as for determining the morphological and/or anatomical changes in the number and density of sensory fibers during various pathological states. Further, these methods are not confined to the staining of only sensory nerve fibers, but can also be used for staining any types of nerve fibers in the skin, bones and other visceral tissue. PMID- 22314688 TI - Rational addition of capping groups to the phosphomolybdate Keggin anion [PMo12O40](3-) by mild, non-aqueous reductive aggregation. AB - Controlled reductive assembly of capped Keggin anions [PMo(12)O(40)(ML(m))(n)](3 ) has been achieved by reduction of [PMo(12)O(40)](3-) with sodium-mercury amalgam in the presence of metal halides, as exemplified by the rational syntheses of mono-capped [PMo(12)O(40){Co(MeCN)(2)}](3-) and bi-capped [PMo(12)O(40)(VO)(2)](3-) and [PMo(12)O(40)Sb(2)](3-). PMID- 22314689 TI - Comparison of whole blood fibrin-based clot tests in thrombelastography and thromboelastometry. AB - BACKGROUND: Fibrin-based clot firmness is measured as maximum amplitude (MA) in the functional fibrinogen (FF) thrombelastographic assay and maximum clot firmness (MCF) in the FIBTEM thromboelastometric assay. Differences between the assays/devices may be clinically significant. Our objective was to compare clot firmness parameters through standard (FF on a thrombelastography device [TEG(r)]; FIBTEM on a thromboelastometry device [ROTEM(r)]) and crossover (FF on ROTEM(r); FIBTEM on TEG(r)) analyses. METHODS: Whole-blood samples from healthy volunteers were subjected to thrombelastography and thromboelastometry analyses. Samples were investigated native and following stepwise dilution with sodium chloride solution (20%, 40%, and 60% dilution). Samples were also assessed after in vitro addition of medications (heparin, protamine, tranexamic acid) and 50% dilution with hydroxyethyl starch, gelatin, sodium chloride, and albumin. RESULTS: FF produced higher values than FIBTEM, regardless of the device, and TEG(r) produced higher values than ROTEM(r), regardless of the assay. With all added medications except heparin 400 U/kg bodyweight, FF MA remained significantly higher (P < 0.05) than FIBTEM MCF, which was largely unchanged. FF MA was significantly reduced (P = 0.04) by high-dose heparin and partially restored with protamine. Fifty percent dilution with hydroxyethyl starch, albumin, and gelatin decreased FIBTEM MCF and FF MA by >50%. CONCLUSIONS: These results demonstrate differences when measuring fibrin-based clotting via the FF and FIBTEM assays on the TEG(r) and ROTEM(r) devices. Point-of-care targeted correction of fibrin-based clotting may be influenced by the assay and device used. For the FF assay, data are lacking. PMID- 22314690 TI - Vocalization assessed by electrolaryngography is unaffected by topical lidocaine anesthesia: a prospective, crossover, randomized, double-blind placebo-controlled study. AB - BACKGROUND: Topical anesthesia of the upper airway is often recommended when difficulty in airway management is anticipated. There are published reports, however, of administration of topical anesthesia resulting in complete loss of airway control. Adverse effects are mostly attributed to interference with involuntary protective airway reflexes, while gross motor function itself generally is thought to be preserved. We hypothesized that if motor control is affected, measurable quantitative changes in vocalization should follow the use of topical anesthesia. METHODS: A prospective, crossover, randomized, double blind study was conducted, in which 24 healthy volunteers each performed 2 vocal exercises, while having their glottic appearance recorded digitally via fiberoptic nasendoscopy. Subjects gargled with 3 test solutions on separate occasions (placebo, 2% lidocaine, and 4% lidocaine) and repeated the vocal exercises and nasendoscopy. The angle between the vocal cords was measured using MB-Ruler(r), and the Laryngograph Speech Studio(r) software was used for vocal parameter analysis. RESULTS: The only significant changes in voice quality occurred between the control and test groups (P = 0.014). No difference could be found between the placebo and lidocaine groups. CONCLUSIONS: Although gargling with local anesthetic affected vocalization, no pharmacological effect attributable to local anesthetic was observed. PMID- 22314691 TI - Contrast echocardiography to differentiate artifact from left atrial thrombus. PMID- 22314692 TI - Noninvasive autoregulation monitoring in a swine model of pediatric cardiac arrest. AB - BACKGROUND: Cerebrovascular autoregulation after resuscitation has not been well studied in an experimental model of pediatric cardiac arrest. Furthermore, developing noninvasive methods of monitoring autoregulation using near-infrared spectroscopy (NIRS) would be clinically useful in guiding neuroprotective hemodynamic management after pediatric cardiac arrest. We tested the hypotheses that the lower limit of autoregulation (LLA) would shift to a higher arterial blood pressure between 1 and 2 days of recovery after cardiac arrest and that the LLA would be detected by NIRS-derived indices of autoregulation in a swine model of pediatric cardiac arrest. We also tested the hypothesis that autoregulation with hypertension would be impaired after cardiac arrest. METHODS: Data on LLA were obtained from neonatal piglets that had undergone hypoxic-asphyxic cardiac arrest and recovery for 1 day (n = 8) or 2 days (n = 8), or that had undergone sham surgery with 2 days of recovery (n = 8). Autoregulation with hypertension was examined in a separate cohort of piglets that underwent hypoxic-asphyxic cardiac arrest (n = 5) or sham surgery (n = 5) with 2 days of recovery. After the recovery period, piglets were reanesthetized, and autoregulation was monitored by standard laser-Doppler flowmetry and autoregulation indices derived from NIRS (the cerebral oximetry [COx] and hemoglobin volume [HVx] indices). The LLA was determined by decreasing blood pressure through inflation of a balloon catheter in the inferior vena cava. Autoregulation during hypertension was evaluated by inflation of an aortic balloon catheter. RESULTS: The LLAs were similar between sham-operated piglets and piglets that recovered for 1 or 2 days after arrest. The NIRS-derived indices accurately detected the LLA determined by laser-Doppler flowmetry. The area under the curve of the receiver operator characteristic curve for cerebral oximetry index was 0.91 at 1 day and 0.92 at 2 days after arrest. The area under the curve for hemoglobin volume index was 0.92 and 0.89 at the respective time points. During induced hypertension, the static rate of autoregulation, defined as the percentage change in cerebrovascular resistance divided by the percentage change in cerebral perfusion pressure, was not different between postarrest and sham-operated piglets. At 2 days recovery from arrest, piglets exhibited neurobehavioral deficits and histologic neuronal injury. CONCLUSIONS: In a swine model of pediatric hypoxic-asphyxic cardiac arrest with confirmed brain damage, the LLA did not differ 1 and 2 days after resuscitation. The NIRS-derived indices accurately detected the LLA in comparison with laser-Doppler flow measurements at those time points. Autoregulation remained functional during hypertension. PMID- 22314693 TI - Poor accuracy of noninvasive cardiac output monitoring using bioimpedance cardiography [PhysioFlow(R)] compared to magnetic resonance imaging in pediatric patients. AB - BACKGROUND: Identification of low cardiac output (CO) states in anesthesia is important because preoperative hemodynamic optimization may improve outcome in surgery. Accurate real-time CO measurement would be useful in optimizing "goal directed" therapy. We sought to evaluate the reliability and accuracy of CO measurement using bioimpedance cardiography (PhysioFlow(r), NeuMeDx, Bristol, PA) in pediatric patients with and without cardiac disease undergoing anesthesia for magnetic resonance imaging (MRI). METHODS: All consenting patients undergoing anesthesia for cardiac MRI were enrolled. After equilibration of anesthesia for >=10 minutes, 6 PhysioFlow electrodes were applied to the patient's chest for continuous real-time monitoring for 10 minutes. Data were stored in 15-second epochs and later averaged offline to obtain CO. Phase contrast MRI measurements of flow volumes in the superior vena cava and ascending and descending aorta were made from a single imaging plane through all 3 vessels at the level of the right pulmonary artery. Both CO measurements were indexed to body surface area. The anesthetic technique was the same for both measurements. Agreement was assessed using Bland-Altman analysis. RESULTS: Thirty-one patients were enrolled and 23 were analyzed. The median age at study was 2.8 years (range, 0.02-8.02 years) and median body surface area was 0.54 m(2) (range, 0.21-1.00 m(2)). Eleven of the 23 patients (48%) were males. Patients were grouped into those with univentricular physiology, 6 of 23 (26%); biventricular physiology with shunt, 3 of 23 (13%); biventricular without shunt, 10 of 23 (43%); and no structural heart disease, 4 of 23 (17%). The mean bias was -0.34 +/- 1.50 L/min/m(2) (P = 0.29). The 95% limits of agreement were -3.21 to +2.69 L/min/m(2). Only 8 of 23 measurements (35%) were within 20% and 14 of 23 measurements (61%) were within 30% of each other. CONCLUSION: PhysioFlow performance was not sufficiently accurate in this population. Modifications of the algorithm and further testing are required before this device can be recommended for routine clinical use in pediatric patients. PMID- 22314694 TI - Incorporating pTGF-beta1/calcium phosphate nanoparticles with fibronectin into 3 dimensional collagen/chitosan scaffolds: efficient, sustained gene delivery to stem cells for chondrogenic differentiation. AB - The objective of this study was to prepare a 3-dimensional nanoparticle gene delivery system (3D-NGDS) based on collagen/chitosan scaffolds, in which plasmid transforming growth factor beta 1 (TGF-beta1)/calcium phosphate nanoparticles mixed with fibronectin (FN) were used to transfect mesenchymal stem cells (MSCs). Scanning electron microscopy was used to characterise the microstructure of 3 dimensional collagen/chitosan scaffolds. An analysis performed to quantify the TGF-b1 concentrations in MSC cultures revealed that the MSCs transfected with the 3D-NGDS showed remarkably high levels of TGF-b1 over long periods, retaining a concentration of TGF-b1 of approximately 10 ng/mL within two weeks, with the highest level (12.6 ng/mL) being observed on the 6th day. An immunohistochemistry analysis for collagen type II revealed that much higher production of collagen II from the 9th to 15th day was observed in the 3D-NGDS-transfected MSCs than that in MSCs transfected by the Lipofectamine 2000 method. The glycosaminoglycan content of the 3D-NGDS was comparable to those treated with TGF-beta1 as well as TGF-beta1 plus dexamethasone, and was significantly higher than those treated with free plasmid and Lipofectamine 2000. A remarkable type I collagen expression inhibition of the 3D-NGDS at day 21 was observed via ELISA. These results suggested that transfection with the 3D-NGDS could successfully induce MSC chondrogenic differentiation in vitro without dexamethasone. In summary, the 3D NGDS could be developed into a promising alternative method to transfer exogenous nucleic acid to MSCs in clinical trials. PMID- 22314695 TI - Chronic kidney disease and mortality risk among older patients with type 2 diabetes mellitus (ZODIAC-24). AB - OBJECTIVE: to investigate the association between a decreased estimated glomerular filtration rate (eGFR), albuminuria and mortality in elderly patients with type 2 diabetes mellitus (T2DM). DESIGN: prospective observational cohort study. SETTING: primary care. SUBJECTS: eight hundred and ten patients, >=65 years with T2DM. Analyses were performed in age strata: 65-75 (n = 471), >75 (n = 339) years. METHODS: Cox proportional hazard modelling was used to investigate the association between eGFR, albuminuria and all-cause and cardiovascular mortality after a median follow-up of 9.8 years. RESULTS: an eGFR <45 and 45-60 ml/min/1.73 m(2) is associated with increased cardiovascular mortality in patients of 65-75 years, hazard ratio (HR): 3.29 (1.58-6.86) and 1.78 (1.09 2.90), respectively; in those >75 years increased cardiovascular mortality was observed when eGFR was <45 ml/min/1.73 m(2): 2.42 (1.47-3.69). Compared with patients of 65-75 years, an eGFR >60 ml/min/1.73 m(2) and normo-albuminuria, fully adjusted HRs for cardiovascular mortality were 2.26 (1.04-4.92) and 4.86 (2.33-10.15) for those aged 65-75 years, an eGFR of 45-60 ml/min/1.73 m(2) and normo-albuminuria or albuminuria, respectively; HRs were 1.33 (0.67-2.66) and 2.01 (1.02-3.94), respectively, for those >75 years. CONCLUSIONS: an eGFR of 45 60 ml/min/1.73 m(2) in T2DM patients is associated with increased mortality in patients aged 65-75 years but not in those >75 years. Albuminuria is associated with increased mortality in patients >65 years. PMID- 22314697 TI - Effect of the overall rotation on the cis-trans isomerization of HONO induced by an external field. AB - Rovibrational eigenenergies of HONO are computed and compared to experimental energies available in the literature. For their computation, we use a previously developed potential energy surface (PES) and a newly derived exact kinetic energy operator (KEO) including the overall rotation for a tetra-atomic molecule in non orthogonal coordinates. In addition, we use the Heidelberg Multi-Configuration Time-Dependent Hartree (MCTDH) package. We compare the experimental rovibrational eigenvalues of HONO available in the literature with those obtained with MCTDH and a previously developed potential energy surface (PES) [F. Richter et al., J. Chem. Phys., 2004, 120, 1306.] for the cis geometry. The effect of the overall rotation on the process studied in our previous work on HONO [F. Richter et al., J. Chem. Phys., 2007, 127, 164315.] leading to the cis->trans isomerization of HONO is investigated. This effect on this process is found to be weak. PMID- 22314696 TI - Inferior physical performance test results of 10,998 men in the MrOS Study is associated with high fracture risk. AB - BACKGROUND: most fractures are preceded by falls. OBJECTIVE: the aim of this study was to determine whether tests of physical performance are associated with fractures. SUBJECTS: a total of 10,998 men aged 65 years or above were recruited. METHODS: questionnaires evaluated falls sustained 12 months before administration of the grip strength test, the timed stand test, the six-metre walk test and the twenty-centimetre narrow walk test. Means with 95% confidence interval (95% CI) are reported. P < 0.05 is a statistically significant difference. RESULTS: fallers with a fracture performed worse than non-fallers on all tests (all P < 0.001). Fallers with a fracture performed worse than fallers with no fractures both on the right-hand-grip strength test and on the six-metre walk test (P < 0.001). A score below -2 standard deviations in the right-hand-grip strength test was associated with an odds ratio of 3.9 (95% CI: 2.1-7.4) for having had a fall with a fracture compared with having had no fall and with an odds ratio of 2.6 (95% CI: 1.3-5.2) for having had a fall with a fracture compared with having had a fall with no fracture. CONCLUSION: the right-hand-grip strength test and the six-metre walk test performed by old men help discriminate fallers with a fracture from both fallers with no fracture and non-fallers. PMID- 22314698 TI - Pseudolaric acid B inhibits inducible cyclooxygenase-2 expression via downregulation of the NF-kappaB pathway in HT-29 cells. AB - PURPOSE: Pseudolaric acid B (PAB) is a diterpene acid isolated from the root and trunk bark of Pseudolaric kaempferi Gordon. Previous work has found that PAB has anti-inflammatory and anti-tumor effects in xenograft models of human hepatocellular carcinoma. The aim of this study is to evaluate the correlation between anti-cancer and anti-inflammatory effects of PAB and its molecular mechanisms on HT-29 cells. METHODS: Production of prostaglandin E2 (PGE2) in HT 29 cells was evaluated by ELISA. mRNA of cyclooxygenase-2 (COX-2) was analyzed by RT-PCR assay. High-content screening (HCS) method was adopted to detect the cytokine mixture (CM)-induced transcription activity of NF-kappaB and STAT3. Western blotting was used to evaluate the protein expression levels of inflammatory mediators induced by CM. After treatment with PAB in various concentrations, the inhibition rate of cell proliferation was measured with sulforhodamine B assays. For the in vivo studies, tumor-bearing models xenografted with HT-29 cells were developed in nude mice, and following oral administration with PAB, tumor inhibition rate was calculated. RESULTS: PAB inhibited the PGE2 production in HT-29 cells significantly (P < 0.05) with similar results detected at the COX-2 mRNA level. Furthermore, PAB suppressed the COX-2 protein expression and significant nuclear translocation of NF-kappaB and STAT3 induced by CM, which correlated with a concomitant degradation of I-kappaB and a decrease in constitutive STAT3 phosphorylation (P < 0.05). Moreover, various concentrations of PAB inhibited the proliferation of HT-29 cells in a dose- and time-dependent manner. In vivo, after treatment with PAB for 17 days, the tumor weight of the 50 and 100 mg/kg treated groups was 0.62 +/- 0.15 and 0.54 +/- 0.06 g, respectively. When compared to the control group (0.82 +/- 0.16 g), the inhibition rate of tumor weight was 24.2% at 50 mg/kg (P < 0.05) and 34.7% at 100 mg/kg (P < 0.001). CONCLUSIONS: PAB shows potential anti-cancer activity in HT-29 cells, and its molecular mechanisms are related to the anti inflammatory action. PMID- 22314699 TI - Sensitization and symptoms associated with soybean exposure in processing plants in South Africa. AB - BACKGROUND: Following the results of a previous study that highlighted the potential for significant levels of dust exposure in South African soybean processing plants, a clinical investigation was undertaken to study the respiratory health of workers in this industry. METHODS: Workers from three soybean-processing plants were studied with a respiratory questionnaire and estimation of atopy and specific soybean IgE. RESULTS: A total of 144 of the 181 (79.6% participation rate) plant employees completed the questionnaire and 136 (75.1%) gave blood samples for analysis of specific IgE. There was a significant association between work-related chest tightness (OR 4.0 [95% CI 1.3-12.6]), work related nasal symptoms (OR 4.3 [95% CI 1.3-14.6]) and cough or chest tightness after handling soybean (OR 3.6 [95% CI 1.1-11.6]) and soybean sensitization. There was a significant association between current exposure to dust during soybean off-loading and "flu-like" illness (OR 2.7 [95% CI 1.0-7.2]), and cough or chest tightness after such work (OR 7.4 [95% CI 2.4-23.6]). The strongest predictor of work related nasal symptoms was sensitization to soybean, the latter strongly predicted by the presence of atopy (OR 34.7 [95% CI 6.6-182.5]). CONCLUSIONS: Exposure and sensitization to soybean were associated with the presence of work related symptoms, including flu-like symptoms, cough, chest tightness, and nasal symptoms. The aetiology of these symptoms and more particularly the best intervention strategies require more detailed investigation. PMID- 22314700 TI - Is it possible to train surgeons for rural Africa? A report of a successful international program. PMID- 22314701 TI - Single-stranded DNA (ssDNA) production in DNA aptamer generation. AB - The discovery that synthetic short chain nucleic acids are capable of selective binding to biological targets has made them to be widely used as molecular recognition elements. These nucleic acids, called aptamers, are comprised of two types, DNA and RNA aptamers, where the DNA aptamer is preferred over the latter due to its stability, making it widely used in a number of applications. However, the success of the DNA selection process through Systematic Evolution of Ligands by Exponential Enrichment (SELEX) experiments is very much dependent on its most critical step, which is the conversion of the dsDNA to ssDNA. There is a plethora of methods available in generating ssDNA from the corresponding dsDNA. These include asymmetric PCR, biotin-streptavidin separation, lambda exonuclease digestion and size separation on denaturing-urea PAGE. Herein, different methods of ssDNA generation following the PCR amplification step in SELEX are reviewed. PMID- 22314702 TI - Identification of helix capping and b-turn motifs from NMR chemical shifts. AB - We present an empirical method for identification of distinct structural motifs in proteins on the basis of experimentally determined backbone and (13)C(beta) chemical shifts. Elements identified include the N-terminal and C-terminal helix capping motifs and five types of beta-turns: I, II, I', II' and VIII. Using a database of proteins of known structure, the NMR chemical shifts, together with the PDB-extracted amino acid preference of the helix capping and beta-turn motifs are used as input data for training an artificial neural network algorithm, which outputs the statistical probability of finding each motif at any given position in the protein. The trained neural networks, contained in the MICS (motif identification from chemical shifts) program, also provide a confidence level for each of their predictions, and values ranging from ca 0.7-0.9 for the Matthews correlation coefficient of its predictions far exceed those attainable by sequence analysis. MICS is anticipated to be useful both in the conventional NMR structure determination process and for enhancing on-going efforts to determine protein structures solely on the basis of chemical shift information, where it can aid in identifying protein database fragments suitable for use in building such structures. PMID- 22314703 TI - Estimating side-chain order in methyl-protonated, perdeuterated proteins via multiple-quantum relaxation violated coherence transfer NMR spectroscopy. AB - Relaxation violated coherence transfer NMR spectroscopy (Tugarinov et al. in J Am Chem Soc 129:1743-1750, 2007) is an established experimental tool for quantitative estimation of the amplitudes of side-chain motions in methyl protonated, highly deuterated proteins. Relaxation violated coherence transfer experiments monitor the buildup of methyl proton multiple-quantum coherences that can be created in magnetically equivalent spin-systems as long as their transverse magnetization components relax with substantially different rates. The rate of this build-up is a reporter of the methyl-bearing side-chain mobility. Although the build-up of multiple-quantum (1)H coherences is monitored in these experiments, the decay of the methyl signal during relaxation delays occurs when methyl proton magnetization is in a single-quantum state. We describe a relaxation violated coherence transfer approach where the relaxation of multiple quantum (1)H-(13)C methyl coherences during the relaxation delay period is quantified. The NMR experiment and the associated fitting procedure that models the time-dependence of the signal build-up, are applicable to the characterization of side-chain order in [(13)CH(3)]-methyl-labeled, highly deuterated protein systems up to ~100 kDa in molecular weight. The feasibility of extracting reliable measures of side-chain order is experimentally verified on methyl-protonated, perdeuterated samples of an 8.5-kDa ubiquitin at 10 degrees C and an 82-kDa Malate Synthase G at 37 degrees C. PMID- 22314704 TI - N-terminal Dbl domain of the RhoGEF, Kalirin. PMID- 22314705 TI - Combining NMR ensembles and molecular dynamics simulations provides more realistic models of protein structures in solution and leads to better chemical shift prediction. AB - While chemical shifts are invaluable for obtaining structural information from proteins, they also offer one of the rare ways to obtain information about protein dynamics. A necessary tool in transforming chemical shifts into structural and dynamic information is chemical shift prediction. In our previous work we developed a method for 4D prediction of protein (1)H chemical shifts in which molecular motions, the 4th dimension, were modeled using molecular dynamics (MD) simulations. Although the approach clearly improved the prediction, the X ray structures and single NMR conformers used in the model cannot be considered fully realistic models of protein in solution. In this work, NMR ensembles (NMRE) were used to expand the conformational space of proteins (e.g. side chains, flexible loops, termini), followed by MD simulations for each conformer to map the local fluctuations. Compared with the non-dynamic model, the NMRE+MD model gave 6-17% lower root-mean-square (RMS) errors for different backbone nuclei. The improved prediction indicates that NMR ensembles with MD simulations can be used to obtain a more realistic picture of protein structures in solutions and moreover underlines the importance of short and long time-scale dynamics for the prediction. The RMS errors of the NMRE+MD model were 0.24, 0.43, 0.98, 1.03, 1.16 and 2.39 ppm for (1)Halpha, (1)HN, (13)Calpha, (13)Cbeta, (13)CO and backbone (15)N chemical shifts, respectively. The model is implemented in the prediction program 4DSPOT, available at http://www.uef.fi/4dspot. PMID- 22314706 TI - Postmortem observation of collagenous lead tip region fibrosis as a rare complication of DBS. AB - BACKGROUND: Despite the widespread effective use of deep brain stimulation (DBS) for various movement and psychiatric disorders, little is known about its safety and tissue responses. METHODS: The University of Florida Deep Brain Stimulation Brain Tissue Network (DBS-BTN) conducted postmortem brain examinations on 26 cases to identify and characterize (using histological techniques) pathologic tissue changes associated with the placement of DBS devices. RESULTS: We report the unusual finding of prominent collagenous fibrosis around the lead tip in a 74 year-old man with idiopathic Parkinson's disease who had bilateral STN-DBS. Histological study confirmed the diagnosis of idiopathic Parkinson's disease, and there was striking, dense collagenous fibrosis at the distal end of the right DBS lead associated with focal hemosiderin deposition, chronic inflammation, and mild gliosis. We have in our brain bank 25 other DBS cases that on examination showed only mild to moderate gliosis and no dramatic tissue response to DBS lead placement. CONCLUSIONS: We are not aware of any prior reports of such a dramatic reaction to DBS placement to date. PMID- 22314707 TI - Quantifying mixing using magnetic resonance imaging. AB - Mixing is a unit operation that combines two or more components into a homogeneous mixture. This work involves mixing two viscous liquid streams using an in-line static mixer. The mixer is a split-and-recombine design that employs shear and extensional flow to increase the interfacial contact between the components. A prototype split-and-recombine (SAR) mixer was constructed by aligning a series of thin laser-cut Poly (methyl methacrylate) (PMMA) plates held in place in a PVC pipe. Mixing in this device is illustrated in the photograph in Fig. 1. Red dye was added to a portion of the test fluid and used as the minor component being mixed into the major (undyed) component. At the inlet of the mixer, the injected layer of tracer fluid is split into two layers as it flows through the mixing section. On each subsequent mixing section, the number of horizontal layers is duplicated. Ultimately, the single stream of dye is uniformly dispersed throughout the cross section of the device. Using a non Newtonian test fluid of 0.2% Carbopol and a doped tracer fluid of similar composition, mixing in the unit is visualized using magnetic resonance imaging (MRI). MRI is a very powerful experimental probe of molecular chemical and physical environment as well as sample structure on the length scales from microns to centimeters. This sensitivity has resulted in broad application of these techniques to characterize physical, chemical and/or biological properties of materials ranging from humans to foods to porous media (1, 2). The equipment and conditions used here are suitable for imaging liquids containing substantial amounts of NMR mobile (1)H such as ordinary water and organic liquids including oils. Traditionally MRI has utilized super conducting magnets which are not suitable for industrial environments and not portable within a laboratory (Fig. 2). Recent advances in magnet technology have permitted the construction of large volume industrially compatible magnets suitable for imaging process flows. Here, MRI provides spatially resolved component concentrations at different axial locations during the mixing process. This work documents real-time mixing of highly viscous fluids via distributive mixing with an application to personal care products. PMID- 22314708 TI - Are family-oriented interventions in Portuguese genetics services a remote possibility? Professionals' views on a multifamily intervention for cancer susceptibility families. AB - This article examines genetics healthcare professionals' opinions about a multifamily psychoeducational programme for hereditary cancer susceptibility families, implemented at a Portuguese genetics service. Their views on how a family-oriented approach is envisioned to be incorporated in Portuguese genetic counselling services are also reported. Six focus groups and three individual interviews were undertaken comprising 30 professionals working in the provision of genetic counselling and genetic counsellor trainees. Participants were given a page-summary describing the intervention and asked to comment the strengths and limitations of the multifamily intervention. All interviews were fully transcribed and analysed using the constant comparison method. The qualitative analysis generated data comprising four thematic categories in relation to the professionals' views: (a) usefulness of the programme; (b) programme's methodological and practical obstacles; (c) genetics services constraints; and (d) suggestions for improving the programme and further family-oriented interventions. We reflect on the reported views examining the intervention, and on how current constraints of genetic services limit the provision of psychosocial support for cancer susceptibility families. The implications of these findings regarding the purpose of genetic counselling are discussed. Results may sensitise stakeholders and policy makers for the need to deliver family-based services in cancer genetic counselling, with adequate planning and collaborative involvement of different professionals. PMID- 22314709 TI - [Ernst Rudin: distinguished scientist, radical racial hygienist]. AB - Ernst Rudin (1874-1952) was one of the founders of psychiatric genetics. From 1931 until 1945, he was Director of the German Institute for Psychiatric Research (Deutsche Forschungsanstalt fur Psychiatrie, DFA) and from 1935 until 1945 President of the German Association of Neurologists and Psychiatrists. The historical knowledge on Rudin is reconsidered, using new sources, and with a focus on Rudin's involvement in the Nazi program of patient killings ("euthanasia"). It is documented that (1) it is a misconception to interpret psychiatric genetics as "instrumentalised" by the Nazi regime; (2) Rudin belonged to the group of psychiatric perpetrators who worked to give the Nazi selection policies scientific authority; (3) Rudin knew early on about the patient killings and refused to support others in their efforts to stop them; and (4) the research in the context of the patient killings carried out by Julius Deussen, a member of Rudin's team at the DFA, was initiated and actively supported by Rudin, and co financed by the DFA. PMID- 22314710 TI - A mathematical model for fluid shear-sensitive 3D tissue construct development. AB - This research studies dynamic culture for 3D tissue construct development with computational fluid dynamics. It proposes a mathematical model to evaluate the impact of flow rates and flow shear stress on cell growth in 3D constructs under perfusion. The modeling results show that dynamic flow, even at flow rate as low as 0.002 cm/s, can support much better mass exchange, higher cell number, and more even cell and nutrient distribution compared to static culture. Higher flow rate can further improve nutrient supply and mass exchange in the construct, promoting better nutritious environment and cell proliferation compared to lower flow rate. In addition, consideration of flow shear stress predicts much higher cell number in the construct compared to that without shear consideration. While the nutrient can dominate shear stress in influencing cell proliferation, the shear effect increases with flow rate. The proposed model helps tissue engineers better understand the cell-flow relationship at the molecular level during dynamic culture. PMID- 22314711 TI - Patchy deletion of Bmpr1a potentiates proximal pulmonary artery remodeling in mice exposed to chronic hypoxia. AB - Reduced vascular expression of bone morphogenetic protein type IA receptor (Bmpr1a) has been found in patients with pulmonary arterial hypertension. Our previous studies in mice with patchy deletion of Bmpr1a in vascular smooth muscle cells and cardiac myocytes showed decreased distal vascular remodeling despite a similar severity of hypoxic pulmonary hypertension (HPH). We speculate increased stiffness from ectopic deposition of collagen in proximal pulmonary arteries might account for HPH. Pulsatile pressure-flow relationships were measured in isolated, ventilated, perfused lungs of SM22alpha;TRE-Cre;R26R;Bmpr1a(flox/flox) (KO) mice and wild-type littermates, following 21 days (hypoxia) and 0 days (control) of chronic hypoxia. Pulmonary vascular impedance, which yields insight into proximal and distal arterial remodeling, was calculated. Reduced Bmpr1a expression had no effect on input impedance Z(0) (P = 0.52) or characteristic impedance Z(C) (P = 0.18) under control conditions; it also had no effect on the decrease in Z(0) via acute rho kinase inhibition. However, following chronic hypoxia, reduced Bmpr1a expression increased Z(C) (P < 0.001) without affecting Z(0) (P = 0.72). These results demonstrate that Bmpr1a deficiency does not significantly alter the hemodynamic function of the distal vasculature or its response to chronic hypoxia but larger, more proximal arteries are affected. In particular, reduced Bmpr1a expression likely decreased dilatation and increased stiffening in response to hypoxia, probably by collagen accumulation. Increased PA stiffness can have a significant impact on right ventricular function. This study illustrates for the first time how proximal pulmonary artery changes in the absence of distal pulmonary artery changes contribute to pulmonary arterial hypertension. PMID- 22314712 TI - The diabetes pandemic. PMID- 22314713 TI - Effect of a high nutrient density diet on long-term weight loss: a retrospective chart review. PMID- 22314714 TI - Cerebral metabolic changes in men after chiropractic spinal manipulation for neck pain. AB - BACKGROUND: Chiropractic spinal manipulation (CSM) is an alternative treatment for back pain. The autonomic nervous system is often involved in spinal dysfunction. Although studies on the effects of CSM have been performed, no chiropractic study has examined regional cerebral metabolism using positron emission tomography (PET). OBJECTIVE: The aim of the present study was to investigate the effects of CSM on brain responses in terms of cerebral glucose metabolic changes measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: Twelve male volunteers were recruited. Brain PET scanning was performed twice on each participant, at resting and after CSM. Questionnaires were used for subjective evaluations. A visual analogue scale (VAS) was rated by participants before and after chiropractic treatment, and muscle tone and salivary amylase were measured. RESULTS: Increased glucose metabolism was observed in the inferior prefrontal cortex, anterior cingulated cortex, and middle temporal gyrus, and decreased glucose metabolism was found in the cerebellar vermis and visual association cortex, in the treatment condition (P < .001). Comparisons of questionnaires indicated a lower stress level and better quality of life in the treatment condition. A significantly lower VAS was noted after CSM. Cervical muscle tone and salivary amylase were decreased after CSM. Conclusion The results of this study suggest that CSM affects regional cerebral glucose metabolism related to sympathetic relaxation and pain reduction. PMID- 22314716 TI - Long-term effects of Bio-Electromagnetic-Energy Regulation therapy on fatigue in patients with multiple sclerosis. AB - BACKGROUND: Electromagnetic-field therapy has beneficial short-term effects in multiple sclerosis (MS) patients with major fatigue, but long-term data are lacking. PRIMARY STUDY OBJECTIVES: To evaluate the long-term effects of a specific electromagnetic therapy device (Bio-Electromagnetic- Energy-Regulation [BEMER]) on MS-related fatigue, we designed a crossover control of a previously performed randomized controlled trial and a long-term open-label follow-up trial. DESIGN AND SETTING: Crossover and open-label follow-up trials at a single neurological outpatient center. PARTICIPANTS: Patients with relapsing-remitting MS who had major fatigue (N = 37 patients). INTERVENTION: After a previous randomized controlled trial (exposure to low-frequency pulsed magnetic fields for 8 min twice daily or to placebo treatment for 12 wk), a crossover from control to treatment for another 12 weeks, followed by an open label follow-up trial to 3 years, were done. PRIMARY OUTCOME MEASURES: The outcome criteria were the Modified Fatigue Impact Scale (MFIS), Fatigue Severity Scale (FSS), German long version of the Center for Epidemiologic Studies Depression Scale (CES-D), Multiple Sclerosis Functional Scale (MSFC), and Expanded Disability Status Scale (EDSS). RESULTS: Patients previously on placebo during the randomized controlled trial experienced significant reductions in fatigue after crossing over to treatment. The MFIS and FSS scores were significantly lower in the open-label group than in the control subjects after follow-up. Participation in the open label treatment was the strongest predictor of low fatigue outcome after followup. Electromagnetic-field therapy was well tolerated. CONCLUSIONS: In this long-term study, a beneficial effect of long-term BEMER therapy on MS fatigue was demonstrated. Electromagnetic-field therapy may be a useful therapeutic modality in MS patients with severe fatigue. PMID- 22314717 TI - Physical causes of anxiety and sleep disorders. PMID- 22314718 TI - Patients' preferences about participation in clinical trials studying complementary and alternative medicine. AB - CONTEXT: Patients' unwillingness to participate in clinical research is one of the main challenges that researchers face today. In Complementary and Alternative Medicine (CAM) research, a pertinent yet understudied question is the attitude of potential participants toward clinical trials that test CAM interventions. OBJECTIVES: To assess patients' attitudes and preferences regarding participation in clinical trials which test CAM rather than conventional treatments. DESIGN: A 78-question, pencil-and-paper survey was conducted in collaboration with the Survey Research Center located in the Division of Biomedical Statistics and Informatics in the Department of Health Sciences Research at Mayo Clinic in Rochester, Minnesota. SETTING: The study took place at Mayo Clinic, an academic medical center for tertiary care in Rochester, Minnesota, USA. PATIENTS OR OTHER PARTICIPANTS: Participants were patients undergoing a general medical evaluation at the Division of General Internal Medicine in the Department of Internal Medicine at Mayo Clinic. INTERVENTION: The researchers designed a cross sectional, point-of-care survey. The study coordinator approached patients and invited them to participate. OUTCOME MEASURES: The study summarized the data for categorical variables, identifying numbers of participants and percentages and comparing two proportions using the Fisher exact test. RESULTS: Out of 485 patients asked to participate, 400 (82%) completed the survey. Respondents were equally as interested in participating in clinical trials testing CAM as they were in trials testing conventional treatments (79% vs 69%, P = .09). For all participants, 107 (27%) were in favor of participating in CAM clinical trials and 118 (30%) were in favor of participating in conventional clinical trials. CONCLUSION: Respondents were interested equally in participating in clinical trials testing CAM vs conventional treatments. PMID- 22314719 TI - Effect of magnetotherapeutic device on pain associated with neck and shoulder stiffness. AB - To examine the effectiveness of a neck-type magnetotherapeutic device (MTD), we performed a study of neck and shoulder pain or stiffness measured with a visual analog scale (VAS) and objective parameters (thermography, deep body thermometry, and a muscle meter). There were 62 patients (29 men and 33 women; mean age, 34 y; range, 21 to 58 y) in the study. The patients were randomly assigned (double blinded) to receive treatment with the MTD or non-MTD. The MTD (maximum magnetic flux density, 55 +/- 5 mT; length, 500 mm; and diameter, 4.5 mm) was applied externally to the site of pain. The non- MTD (0 mT; 500 mm; and diameter, 4.5 mm) was applied as a sham control. All patients received treatment for 7 days. In MTD patients, significant pain relief was observed 3 hours after beginning treatment compared with before treatment. Skin surface and deep body temperatures were significantly increased from the baseline values in the MTD group but not in the non- MTD group. The average values of VAS improvement, skin temperature, and deep body temperature in the painful area were significantly greater, and the average value of muscle stiffness was significantly lower in the MTD group than in the non- MTD group 7 days after beginning treatment. PMID- 22314720 TI - The guardians of opinion. PMID- 22314721 TI - [Treatment must vary depending on age and sex]. PMID- 22314722 TI - [Is it dangerous to train hard?]. PMID- 22314723 TI - [Individual genome sequencing]. PMID- 22314724 TI - [How to diagnose a heart attack in 2012?]. PMID- 22314725 TI - [Vaginal samples best in genital chlamydia infections]. PMID- 22314726 TI - [Unsatisfactory doping analysis]. PMID- 22314727 TI - [Alternative detection of agents]. PMID- 22314728 TI - [Future publishing form or modern trash?]. PMID- 22314730 TI - Physical contact with the ground is good for your health. PMID- 22314731 TI - [Peer support for hospital physicians]. PMID- 22314732 TI - Somatocognitive therapy for chronic pelvic pain. PMID- 22314733 TI - [Better information--plea from relatives]. PMID- 22314734 TI - [Fixed limits for central stimulants in traffic]. PMID- 22314735 TI - [Differences in referral rates do not threaten the goal of equity in health care]. PMID- 22314736 TI - Digital volume tomography of the facial skeleton. PMID- 22314737 TI - [Gender- and age-related differences in dosage and serum concentration of psychotropic drugs]. AB - BACKGROUND: The dose recommendations in the Norwegian Pharmaceutical Product Compendium (Felleskatalogen) are not gender-specific, despite evidence of gender dependent differences in the metabolism of a number of drugs. The purpose of this study was to investigate the extent to which age and gender influence the prescription and serum concentration of psychotropic drugs. MATERIAL AND METHOD: The prescribed doses and serum concentrations of antidepressant, antipsychotic and antiepileptic drugs were studied in relation to age and gender in 1533 patients. RESULTS: Elderly women (>= 65 years) were given somewhat lower doses of antidepressant drugs, but they had significantly higher serum concentrations than younger patients of either gender. Antidepressant drugs were prescribed in fairly high doses in the study population; the median number of defined daily doses was 1.5. INTERPRETATION: The study suggests that when prescribing drugs, Norwegian physicians do not take sufficient account of the effect of age and gender on the pharmacokinetics of antidepressant drugs. PMID- 22314738 TI - Prescribing contraception for young women. AB - BACKGROUND: Since 2002, specially qualified nursing sisters and midwives have had the right to prescribe contraceptive pills for women aged 16 to 19. This arrangement has since been expanded to cover hormonal contraception, with the exception of the hormonal coil. The purpose of this study is to evaluate the arrangement. MATERIAL AND METHOD: The prescription register uses pseudonyms and contains a number of facts about user, medication and prescriber. A database of women born in 1989, totalling 29,821, has been designed as a unit for analysis. RESULTS: 75 and 79% of the cohort had filled at least one prescription for contraceptive pills or hormonal contraception by the end of the calendar year in which they turned 19. Almost 12% had filled at least one prescription for the mini-pill, while far fewer had filled prescriptions for vaginal hormone ring, contraceptive injection, contraceptive patch or hormonal coil. Doctors issued two third of the prescriptions. Nursing sisters wrote more prescriptions than doctors for the age group 17-18. The period of time during which they had been using the contraceptive pill and the mini-pill did not depend on who prescribed them. INTERPRETATION: The fact that close to 80% of the cohort born in 1989 has filled at least one prescription for hormonal contraception shows that there is a high degree of awareness about preventing unplanned pregnancy. Extending the right to write prescriptions to nurses and midwives has increased the availability of contraception, and young women are taking advantage of this option. PMID- 22314739 TI - Atrial fibrillation, physical activity and endurance training. AB - INTRODUCTION: Clinical practice and the results of some studies may indicate that physical exercise in the form of endurance training may influence the development of atrial fibrillation (AF). The aim of this paper is to evaluate the scientific background for the hypothesis that there is a connection between physical activity and AF. MATERIAL AND METHOD: This paper is a review article based on searches in PubMed on specific topics, limited to the period 1995 through March 2011. We found 17 original articles and three relatively recent reviews. Each was read by at least two of the authors and then discussed. Seven of the original articles were excluded for methodological reasons, and we therefore discuss the other ten. RESULTS: We found support for the hypothesis that systematic high intensity endurance training such as running can increase the risk of AF, whereas the studies provide no evidence that less intensive physical exercise such as walking increases the risk. Several of the studies have methodological weaknesses. INTERPRETATION: Important questions remain unanswered. There is a need for more studies that can shed light on the connection between training intensity, total volume of intensive endurance training, age-related changes and AF. Studies that include women are also needed. PMID- 22314740 TI - [Palatal myoclonus]. PMID- 22314741 TI - [Use of slow-release injections to administer antipsychotic drugs]. AB - Compliance is a major problem in connection with the use of antipsychotics. Slow release injections were therefore developed in the 1960s. As a result of a substantial reduction of water solubility, the active substance diffuses slowly from the injection site so that a therapeutic serum concentration is assured throughout the period. New studies show that this treatment can reduce the risk of patients requiring hospitalisation and of psychotic relapses compared with the use of tablets. PMID- 22314742 TI - [Dosage of ordinary medication prior to elective surgery]. AB - Patients will in general benefit from their ordinary medication in the perioperative phase. However, exceptions and special precautions are justified with drugs that may have effects, side-effects or interactions, which are particularly beneficial or harmful during a perioperative course. This includes drugs with thrombotic or bleeding potential, antidiabetics, psychopharmaca and some of the drugs used for prophylaxis and treatment of cardiovascular disease. In such cases individual advice on dosage should be given. PMID- 22314743 TI - [A man in his sixties with hoarseness, difficulty breathing and chest pain]. PMID- 22314744 TI - [The usual is most common, but the rare occurs]. PMID- 22314745 TI - Quality and priorities in the health services. PMID- 22314746 TI - Influenza, krimfarang and A(H1N1)pdm09. PMID- 22314747 TI - [Petitioning for prosecution in the event of violation of the requirement to provide responsible health care]. AB - BACKGROUND: The Norwegian Board of Health Supervision can petition for prosecution of health care personnel or facilities. The purpose of the survey is to find out what circumstances will prompt the Norwegian Board of Health Supervision to petition for prosecution of doctors and/or facilities for violation of the requirement of responsible conduct, how often this happens and what the outcome is. MATERIAL AND METHOD: Petitions for prosecution in the period 1 February 2002 - 31 October 2008 were reviewed. The data stem mainly from two databases containing about 11 500 cases brought before the Norwegian Board of Health Supervision. RESULTS: During the period, the Boards of Health Supervision at county level petitioned for prosecution in some 7,700 cases where doctors and/or facilities had failed to provide responsible health care. Unsound professional practice was found in about 2400 cases. The Board of Health Supervision petitioned for 19 prosecutions in 16 cases (0.7 %), in 9 of them against doctors and in 10 against facilities. Of the cases against doctors, four ended with fines, four were dismissed and in one a ruling has not yet been handed down. Eight facilities were fined, while the cases against two of them were dismissed. The number of petitions for prosecution has shown a declining tendency during the period. INTERPRETATION: The initiation of criminal proceedings against doctors and facilities is relegated by the Norwegian Board of Health Supervision to a minor position among its supervisory activities. PMID- 22314749 TI - Three-component self-assembly of a series of triply interlocked Pd12 coordination prisms and their non-interlocked Pd6 analogues. AB - Template-assisted formation of multicomponent Pd(6) coordination prisms and formation of their self-templated triply interlocked Pd(12) analogues in the absence of an external template have been established in a single step through Pd N/Pd-O coordination. Treatment of cis-[Pd(en)(NO(3))(2)] with K(3) tma and linear pillar 4,4'-bpy (en=ethylenediamine, H(3) tma=benzene-1,3,5-tricarboxylic acid, 4,4'-bpy=4,4'-bipyridine) gave intercalated coordination cage [{Pd(en)}(6)(bpy)(3)(tma)(2)](2)[NO(3)](12) (1) exclusively, whereas the same reaction in the presence of H(3) tma as an aromatic guest gave a H(3) tma encapsulating non-interlocked discrete Pd(6) molecular prism [{Pd(en)}(6)(bpy)(3)(tma)(2)(H(3)tma)(2)][NO(3)](6) (2). Though the same reaction using cis-[Pd(NO(3))(2)(pn)] (pn=propane-1,2-diamine) instead of cis [Pd(en)(NO(3))(2)] gave triply interlocked coordination cage [{Pd(pn)}(6)(bpy)(3)(tma)(2)](2)[NO(3)](12) (3) along with non-interlocked Pd(6) analogue [{Pd(pn)}(6)(bpy)(3) (tma)(2)](NO(3))(6) (3'), and the presence of H(3) tma as a guest gave H(3) tma-encapsulating molecular prism [{Pd(pn)}(6)(bpy)(3)(tma)(2)(H(3) tma)(2)][NO(3)](6) (4) exclusively. In solution, the amount of 3' decreases as the temperature is decreased, and in the solid state 3 is the sole product. Notably, an analogous reaction using the relatively short pillar pz (pz=pyrazine) instead of 4,4'-bpy gave triply interlocked coordination cage [{Pd(pn)}(6) (pz)(3)(tma)(2)](2)[NO(3)](12) (5) as the single product. Interestingly, the same reaction using slightly more bulky cis-[Pd(NO(3))(2)(tmen)] (tmen=N,N,N',N'-tetramethylethylene diamine) instead of cis-[Pd(NO(3))(2)(pn)] gave non-interlocked [{Pd(tmen)}(6)(pz)(3)(tma)(2)][NO(3)](6) (6) exclusively. Complexes 1, 3, and 5 represent the first examples of template-free triply interlocked molecular prisms obtained through multicomponent self-assembly. Formation of the complexes was supported by IR and multinuclear NMR ((1)H and (13)C) spectroscopy. Formation of guest-encapsulating complexes (2 and 4) was confirmed by 2D DOSY and ROESY NMR spectroscopic analyses, whereas for complexes 1, 3, 5, and 6 single-crystal X-ray diffraction techniques unambiguously confirmed their formation. The gross geometries of H(3) tma-encapsulating complexes 2 and 4 were obtained by universal force field (UFF) simulations. PMID- 22314750 TI - Carotid Artery Stenting Versus Carotid Endarterectomy: Post CREST. AB - The risk of stroke associated with carotid artery stenosis can be reduced with carotid endarterectomy or carotid artery stenting in carefully selected patients. While surgery has been the traditional treatment there have been many trials comparing carotid endarterectomy with carotid artery stenting, and stenting has shown promising results for certain patient populations. This article reviews the natural history of carotid artery stenosis, the data supporting carotid endarterectomy, trials directly comparing surgery to stenting, and current recommendations for each modality. PMID- 22314751 TI - An electrochemical DNA biosensor based on the "Y" junction structure and restriction endonuclease-aided target recycling strategy. AB - Based on the "Y" junction structure and restriction endonuclease-aided target recycling strategy, an electrochemical biosensor for DNA detection was developed. This universal biosensor was suitable for detecting different sequences of target DNA by changing the sequence of capture and assistant strands. PMID- 22314752 TI - Primary spinal marginal zone lymphoma: case report and review of the literature. AB - BACKGROUND AND IMPORTANCE: Marginal zone lymphoma (MZL) describes a heterogeneous group of indolent B-cell lymphomas. The World Health Organization recognizes 3 types of MZLs: splenic MZL, nodal MZL, and extranodal MZL of mucosa-associated lymphoid tissue. There is no consensus on the optimal adjuvant treatment modalities for intracranial primary MZLs. To date, no case of spinal primary MZL has been reported. CLINICAL PRESENTATION: We present the first case of spinal MZL diagnosed in a 65-year-old man with progressive paraparesis. He underwent surgical removal of the main spinal tumor mass, which extended epidurally from vertebral body T3 to T7. Surgery was followed by 10 sessions of local irradiation for a total dose of 31 Gy. On long-term follow-up in 2010, the patient was in good health without any signs of residual or recurrent disease. Twenty-seven publications reporting on 61 cases of intracranial primary MZL were identified and reviewed. In the majority of cases of marginal zone B-cell lymphoma, adjuvant radiotherapy was used, with some combining radiotherapy and chemotherapy after surgical removal of the bulk of the main tumor. Long-term follow-up in most patients showed no evidence of disease and clinical well-being years after the initial diagnosis. CONCLUSION: Chemotherapy and/or radiation have been used in larger case series. Although there is no defined treatment guideline for this rare disease entity, our review of the literature suggests a favorable prognosis when combining surgical and adjuvant radiotherapy approaches. PMID- 22314753 TI - The utility of bone cement to prevent lead migration with minimally invasive placement of spinal cord stimulator laminectomy leads. AB - BACKGROUND: Lead migration is a significant concern with spinal cord stimulator (SCS) placement with rates ranging from 10% to 60%. OBJECTIVE: To describe a novel technique using bone cement at the laminotomy site to help prevent lead migration after minimally invasive placement of laminectomy paddle leads and to present our short-term results. METHODS: A review of a prospectively maintained database identified all patients who underwent minimally invasive placement of laminectomy leads with the use of bone cement. All procedures were performed between July 2008 and August 2010 with conscious sedation and local anesthetic. Intraoperative testing was performed to confirm good pain coverage. A small volume of bone cement (1-3 cm) was then placed to cover the laminectomy defect. Radiographic and clinical follow-up was assessed. RESULTS: Forty-two patients (mean age, 58.0 years) underwent 42 procedures. Back pain (88.1%) and leg pain (88.6%) were the most common presenting symptoms. No intraoperative complications were noted. Two patients (4.8%) required removal of their devices because of nonhealing wounds. All patients were followed up for a minimum of 6 months, and no cases of clinical or radiographic lead migration were seen at the time of publication. CONCLUSION: We present a novel technique in the hopes of decreasing the incidence of lead migration after minimally invasive placement of spinal cord stimulator laminectomy paddle leads. Our results have been promising thus far with no cases of lead migration. PMID- 22314754 TI - Motion preservation and clinical outcome of porous coated motion cervical disk arthroplasty. AB - BACKGROUND: Artificial cervical disk replacements are commonly used to treat radiculomyelopathy caused by degenerative disk disease. However, long-term disk mobility and an effect on adjacent segment disease have yet to be demonstrated. We report improvements in clinical outcome after disk replacement but also demonstrate potential limitations. OBJECTIVE: To review clinical and radiological outcomes after diskectomy and disk replacement with the Porous Coated Motion (PCM) artificial cervical disk. METHODS: A retrospective review was done of consecutive patients who underwent 1- or 2-level PCM disk replacements. The following criteria were studied: arm pain, neck pain, Neck Disability Index and Short Form-36 questionnaires, and flexion-extension radiographs up to 2 years after surgery. RESULTS: Eighty PCM artificial disks were implanted in 53 patients. Only 17 disks (21%) maintained physiological movement, and complete fusion was seen in 18.8%. One disk replacement was revised because of anterior displacement. There were no complications of infection, cerebrospinal fluid leak, dysphagia, or hoarse voice. Arm and neck pain improved significantly after diskectomy, but Neck Disability Index questionnaires demonstrated a slight improvement that was not sustained by 2 years. Short Form-36 scores demonstrated a trend toward better outcome with time, but it was significant only for the mental domain. CONCLUSION: Clinical improvement was seen after PCM disk replacement, but adequate range of movement was sustained in only 21% of disk replacements over time. Unclear long-term results of this and other disk replacements suggest caution in adopting these new devices as the gold standard. PMID- 22314755 TI - Fragment density functional theory calculation of NMR chemical shifts for proteins with implicit solvation. AB - Fragment density functional theory (DFT) calculation of NMR chemical shifts for several proteins (Trp-cage, Pin1 WW domain, the third IgG-binding domain of Protein G (GB3) and human ubiquitin) has been carried out. The present study is based on a recently developed automatic fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) approach but the solvent effects are included by using the PB (Poisson-Boltzmann) model. Our calculated chemical shifts of (1)H and (13)C for these four proteins are in excellent agreement with experimentally measured values and represent clear improvement over that from the gas phase calculation. However, although the inclusion of the solvent effect also improves the computed chemical shifts of (15)N, the results do not agree with experimental values as well as (1)H and (13)C. Our study also demonstrates that AF-QM/MM calculated results accurately reproduce the separation of alpha-helical and beta-sheet chemical shifts for (13)C(alpha) atoms in proteins, and using the (1)H chemical shift to discriminate the native structure of proteins from decoys is quite remarkable. PMID- 22314756 TI - Antibody-biotemplated HgS nanoparticles: extremely sensitive labels for atomic fluorescence spectrometric immunoassay. AB - In this work, antibody goat anti-human IgG as a scaffold was employed for the synthesis and biofunctionalization of HgS nanoparticles (NPs) via a facile one pot process. After a complete sandwich-type immunoreaction among primary antibody, human IgG and secondary antibody labeled with HgS NPs, a large number of mercury ions released from captured HgS NPs dissolution were quantitatively detected by chemical vapor generation atomic fluorescence spectrometry (CVG-AFS). Taking advantage of the signal amplification property of HgS NPs and the high sensitivity of CVG-AFS, the assay detected human IgG with a limit of detection (S/N = 3) of 0.6 ng mL(-1) (4.0 fmol mL(-1) or 0.4 fmol) and the response was linear over a dynamic range from 1.0 to 5.0 * 10(4) ng mL(-1) with a correlation coefficient of 0.996. A relative standard deviation (RSD) of 1.0 * 10(2) ng mL( 1) human IgG was 1.5% for within-batch (intra-assay) and 4.5% for between-batch (inter-assay). Other proteins, such as goat anti-rabbit IgG, goat anti-human IgG, rabbit anti-human IgG, carcinoembryonic (CEA), alpha-fetoprotein (AFP), human serum albumin (HSA) and bovine serum albumin (BSA) did not significantly interfere with the assay for human IgG. The analytical result of HgS NPs with AFS based immunoassay technology for the quantification of human IgG in human serum from patients is in good agreement with the result obtained by conventional immunoturbidimetric method. The consequence shows that the novel immunosensor possessed satisfactory precision, extremely high sensitivity, high selectivity and could be applied for the quantification analysis of real samples. PMID- 22314757 TI - Trampling, defoliation and physiological integration affect growth, morphological and mechanical properties of a root-suckering clonal tree. AB - BACKGROUND AND AIMS: Grazing is a complex process involving the simultaneous occurrence of both trampling and defoliation. Clonal plants are a common feature of heavily grazed ecosystems where large herbivores inflict the simultaneous pressures of trampling and defoliation on the vegetation. We test the hypothesis that physiological integration (resource sharing between interconnected ramets) may help plants to deal with the interactive effects of trampling and defoliation. METHODS: In a field study, small and large ramets of the root suckering clonal tree Populus simonii were subjected to two levels of trampling and defoliation, while connected or disconnected to other ramets. Plant responses were quantified via survival, growth, morphological and stem mechanical traits. KEY RESULTS: Disconnection and trampling increased mortality, especially in small ramets. Trampling increased stem length, basal diameter, fibrous root mass, stem stiffness and resistance to deflection in connected ramets, but decreased them in disconnected ones. Trampling decreased vertical height more in disconnected than in connected ramets, and reduced stem mass in disconnected ramets but not in connected ramets. Defoliation reduced basal diameter, leaf mass, stem mass and leaf area ratio, but did not interact with trampling or disconnection. CONCLUSIONS: Although clonal integration did not influence defoliation response, it did alleviate the effects of trampling. We suggest that by facilitating resource transport between ramets, clonal integration compensates for trampling induced damage to fine roots. PMID- 22314758 TI - Gambling prevention program among children. AB - Gambling becomes a more frequent activity among children as they have an easy access to the world of the games. In the same time children are at a higher risk for developing problem and/or pathological gambling having erroneous information about how games of chance and games of skill work. The purpose of the study was to compare the influence of specific primary prevention with rational emotive education (REE) on the subjects' knowledge about games. The experimental design randomly assigned children (N = 81, age 12-13, 37 male and 44 female) into three groups: 1. control, 2. specific information about games using the interactive software "Amazing Chateau", and 3. REE. All children completed a questionnaire with 38 items at the beginning of the study and after 10 weekly interventional meetings. Each item had three answering options, children choosing only one correct answer. Findings indicated that the use of the software significantly improved subjects' knowledge about gambling and corrected their information about how games work. The results of the study confirmed that using specific primary prevention tools for changing erroneous conceptions about games is more efficient than using only REE. The implications of these results for the prevention of gambling problems especially in schools are discussed. PMID- 22314759 TI - [Evaluation of anosognosia in Alzheimer's disease]. AB - AIMS: To compare the prevalence of anosognosia in patients with Alzheimer's disease (AD) using two different evaluation methodologies, to analyse the discrepancy between them and to determine the variables associated with this discrepancy. PATIENTS AND METHODS: The methodology involved a cross-sectional, observational study conducted in patients with AD. The Anosognosia Questionnaire Dementia (AQ-D) and the Experimenter Rating Scale (ERS) were administered. Clinical and sociodemographic information was recorded about both the patient and his/her caregiver by means of standardised instruments. Prevalence was determined with each instrument and the degree of agreement between them was then established. A variable called 'agreement/non-agreement' was created and a logistic regression model was adjusted to determine the variables associated to the discrepancy. RESULTS: The prevalence of anosognosia in the mild cases was 13.6% (95% confidence interval, 95% CI = 5.5-21.7) and 17.3% (95% CI = 8.4-26.1), and 44.2% (95% CI = 28.2-60.2) and 55.8% (95% CI = 38.8-71.8) in the moderate cases, according to the ERS and the AQ-D, respectively. The degree of agreement between the two measurements yielded a kappa-value of 0.7. The regression model with the discrepancy between the ERS and the AQ-D as the dependent variable was associated to a lower functional capacity (odds ratio = 0.080; 95% CI = 0.855 0.997; p = 0.042). CONCLUSIONS: The data from the study showed an increase in the prevalence of anosognosia linked to the severity and a higher disagreement in its evaluation with two different methods as the degree of the patient's functional disability increased. PMID- 22314760 TI - [Cognitive and executive dysfunctions in cocaine dependence: a case-control study]. AB - INTRODUCTION: In the past, various studies have related chronic cocaine use to diverse types of neuropsychological impairment. However, the majority of these studies offer partial results using batteries of tests of little ecological weight. AIM: To investigate neuropsychological impairment (and of executive functions in particular) amongst severe chronic cocaine users, measured by means of more ecological tests and in a more global manner, taking confounding factors into account, such as age, years of schooling, gender, race, opioid dependence and alcohol consumption. SUBJECTS AND METHODS: We performed an observational study, comparing the cocaine dependence group (n = 24) with a non-cocaine use control group (n = 27). RESULTS: The principal results revealed significant differences in the direct and reverse digit span tests (p = 0.008 and p < 0.001 respectively), and in the Cards Test (p < 0.001). They also showed a significance result in the Zoo Map Test (p = 0.001), and in different measurements but not in all forming part of the Wisconsin test (number of correct responses and number of errors). CONCLUSIONS: These results confirm that the chronic use of cocaine per se causes neuropsychological impairment that is manifested in classical and ecologically-valid tests. This impairment may influence patients' functionality and prognosis, and also therapeutic failure. PMID- 22314761 TI - [Development and response to intravenous treatment with tissue plasminogen activator with regard to referral hospitals. The experience of a stroke referral unit]. AB - INTRODUCTION: The intravenous administration of tissue plasminogen inhibitor is a safe and effective treatment for patients with an acute ischaemic stroke. The prognosis depends on a number of factors, the time that elapses between the onset of the stroke and its administration being one of those with the greatest impact. PATIENTS AND METHODS: This is a prospective observational study of the patients who received intravenous fibrinolysis in our stroke unit between June 2007 and December 2010. The patients were divided into two groups, a distinction being made between those who went directly to AE at our hospital and those who were referred from other hospitals in Extremadura. The baseline characteristics, response to treatment and development in each group were compared. RESULTS: The patients who came from outside our health district were mainly males, with a TACI type stroke and they presented higher scores on the National Institutes of Health Stroke Scale (NIHSS). The time elapsed prior to administration of the fibrinolysis was shorter in the patients from our health district. The NIHSS score on discharge was higher in patients who came from another health district, but there were no differences in the Rankin scale at three months or in the mortality rate. CONCLUSIONS: Patients submitted to fibrinolysis who come from another hospital score higher on the NIHSS on discharge. This is probably due to a bias in the selection of the patients, since those referred are mainly males, who have a poorer clinical situation on admission and receive treatment in a significantly longer time interval following the onset of symptoms. PMID- 22314762 TI - Impact of pediatric epilepsy surgery on intellectual efficiency. AB - INTRODUCTION: Epilepsy surgery may be a promising alternative therapy for seizure control in patients with refractory seizures, resistant to medication. Cognitive outcome is another important factor in favor of the surgical decision. AIM: To investigate the correlation between seizure outcome and cognitive outcome after epilepsy surgery in a pediatric population. PATIENTS AND METHODS: A total of 59 pediatric patients were retrospectively assessed with the WISC-III (Full Scale, Verbal Scale and Performance Scale) before and, at least, 6 months after surgery. Patients were divided into two groups according whether or not improvement of seizure control after surgery. Data collected for each child included: epileptic syndrome, etiology, age at epilepsy onset, duration of epilepsy and seizure frequency. RESULTS: Comparison using a MANOVA test revealed significant differences across pre-operative Full Scale, Verbal Scale and Performance Scale (p = 0.01) with seizure reduction group performing better than no seizure reduction group. Seizure improvement group achieved significant Performance Scale improvement (p = 0.01) and no seizure improvement group showed significant Verbal Scale worsened after surgery (p = 0.01). CONCLUSIONS: Our results suggest that the success of the epilepsy surgery in childhood when the seizure control is achieved may also provide an improvement in the Performance Scale whereas the seizure maintenance may worsen the Verbal Scale. PMID- 22314763 TI - [Familial hemiplegic migraine type 2: two paediatric case reports]. AB - INTRODUCTION: Familial hemiplegic migraine is a rare subtype of migraine with aura that includes, as it progresses, a motor defect together with visual or sensory symptoms or speech disorders. It may be associated to symptoms such as basilar migraine, coma and convulsions. Familial hemiplegic migraine type 2 accounts for 25% of them. CASE REPORTS: Two patients, who started at the age of 4 years with episodes of motor deficits or seizures, together with an important sensory disorder that lasted for hours, which were sometimes triggered by banal traumatic injuries. A detailed description of the clinical and developmental features, as well as the studies conducted, is provided. The genetic study revealed mutations in gene ATP1A2: in one case this consisted in a nucleotide substitution in exon 18 (G2501A) that had already been reported, while in the other case there was a previously unknown change (c.381+3 G>T) in intron 4. CONCLUSIONS: We recommend that this condition should be suspected when a disagreement between the duration or the severity of the seizures and the duration and characteristics of the ensuing stupor is detected. PMID- 22314764 TI - [Fibromyalgia and sleep: a review]. AB - INTRODUCTION: Although medical literature has devoted little attention to sleep compared to other symptoms of fibro-myalgia, the American College of Rheumatology has recently proposed that sleep should be a central aspect of the clinical assessment of fibromyalgia. Despite this, no comprehensive reviews have encompassed the physiopathological, psycho-social and therapeutic aspects of the relationship between sleep and fibromyalgia. DEVELOPMENT: A bibliographic search of the terms 'fibromyalgia' and 'sleep' was made in the platforms Scopus and OVID (Medline, PsychINFO and Ovid Nursing Database) from 1 January 1990 to 31 August 2011. After applying certain inclusion criteria, 112 records were selected. CONCLUSIONS: The importance of sleep in this syndrome is increasingly being understood thanks to the progress made in research on fibromyalgia and the use of biopsychosocial explanatory models. Many studies have shown complex inter-actions between sleep disturbances, neuroendocrine and immune abnormalities and the clinical symptoms present in fibromyalgia. Such interactions suggest that sleep disturbances may be both a cause and a consequence of fibromyalgia. Although sleep improvement contributes to alleviating various symptoms of fibromyalgia, there are few effective drugs available and their use has some disadvantages. Regarding other non-drug therapies, it is important to highlight the promising findings of cognitive-behavioral therapy and aerobic exercise. Future research should determine the advantages of each of these treatments and assess their cost effectiveness. PMID- 22314765 TI - [X-chromosome-linked ichthyosis associated to epilepsy, hyperactivity, autism and mental retardation, due to the Xp22.31 microdeletion]. AB - X-chromosome-linked ichthyosis is caused by mutation or deletion of the STS gene associated with a deficiency of the enzyme steroid sulphatase, located in the distal part of the short arm of the X chromosome (Xp22.3-pter), close to the pseudo-autosomal region. Depending on its size, it can present as an isolated entity or combined with a syndrome caused by neighbouring genes, thus associating itself with other monogenic diseases as well as other mental disorders. The most relevant findings from the literature review are the importance of the Xp22.3 pter region and the higher incidence of neurological disorders among males (attention deficit hyperactivity disorder, autism and X-linked mental retardation). The role and implication of these genes in the disease are discussed and the authors suggest a possible contribution of the gene PNPLA4, which was originally described as GS2 and codes for calcium-independent phospholipase A2 beta, involved in lipoprotein metabolism, as one of the causes of autism. Improvements have been observed following treatment with citicoline, thanks to the role this nootropic plays in the biosynthesis of structural phospholipids involved in the formation and repair of the neuronal membrane. PMID- 22314766 TI - [Transcranial duplex in moyamoya disease]. PMID- 22314767 TI - [Dementia associated to paradichlorobenzene poisoning]. PMID- 22314768 TI - [Tectal glioma, autism and the use of jokes]. PMID- 22314769 TI - [Management of atypical lesions of the brain stem in children with neurofibromatosis type 1]. PMID- 22314770 TI - [Some clarifications regarding botulinum toxin type A units]. PMID- 22314773 TI - Mercury levels in feed and muscle of farmed tilapia. AB - BACKGROUND: Fish consumption is considered the most important source of contaminant exposure for humans beings, and farmed fish can be exposed to contaminants via feed supply. METHODS: Total mercury concentrations (THg) were determined in the muscle, liver, and feed of farmed Nile tilapia (juveniles and adults) from four different fish farms in Brazil (net cages and intensive tanks systems), by a flow injection mercury system. RESULTS: Mercury concentrations observed in fish muscle were markedly lower (13.5-30.5 ug kg(-1)) than the values recommended by ANVISA/MAPA for edible part of fish (500 ug kg(-1)), and in the liver the concentrations found were higher than in the muscle. CONCLUSIONS: These low levels of THg in farmed tilapia may be due to the low THg concentrations found in the analyzed fish feed, that ranged from 5.2 to 33.2 ug kg(-1), below the limit of 100 ug kg(-1) established by the European Commission. PMID- 22314772 TI - The association between Mediterranean diet adherence and Parkinson's disease. AB - BACKGROUND: Recent studies have demonstrated an association between a Mediterranean-type diet and Alzheimer's risk. We assessed the association between Mediterranean-type diet adherence and Parkinson's disease (PD) status. METHODS: Two hundred and fifty-seven PD participants and 198 controls completed the Willett semiquantitative questionnaire that quantifies diet during the past year. Scores were calculated using a 9-point scale; higher scores indicated greater adherence to the Mediterranean-type diet. Logistic regression models were used to assess the association between PD status and Mediterranean-type diet, adjusting for caloric intake, age, sex, education, and ethnicity. Adjusted linear regression models were used to examine the association between Mediterranean-type diet adherence and PD age at onset. RESULTS: Higher Mediterranean-type diet adherence was associated with reduced odds for PD after adjustment for all covariates (OR, 0.86; 95% CI, 0.77-0.97; P = .010). Lower Mediterranean-type diet score was associated with earlier PD age at onset (beta = 1.09; P = .006). CONCLUSIONS: PD patients adhere less than controls to a Mediterranean-type diet. Dietary behavior may be associated with age at onset. PMID- 22314774 TI - Endovascular renal artery denervation: why, when, and how? AB - Endovascular renal artery denervation (ERAD) is a new procedure to reduce renal and systemic sympathetic overactivity in hypertensive patients. The role of sympathetic overactivity is recognized since a long time as being one the contributor of human hypertension. In support of this view, several studies in experimental models of hypertension in animal as well as hypertensive human subjects have demonstrated that sympathetic overactivity plays a central role in hypertension catheter based renal denervation is now possible, and this procedure may provide a useful adjunct for the management of patients with drug-resistant primary hypertension. Following a cohort study, the results of an open label randomized control trial have been published showing very encouraging results. The purpose of this paper is to help interventionalists to better understand the medical and technical issues related to this new intervention. It is most likely that as underlined in a recent editorial several other technical approaches may appear in the future, however because this is the only technique that is available today, we will focus on radiofrequency based technique. PMID- 22314775 TI - Posttraumatic basilar artery herniation associated with dissecting aneurysm formation: follow-up over 20 months. PMID- 22314776 TI - Life-threatening Arterioenteric fistula bleeding treated by embolization. PMID- 22314777 TI - POTS due to excessive venous pooling in an enlarged inferior vena cava. AB - Postural tachycardia syndrome (POTS) is a form of orthostatic intolerance characterized by a marked increase in heart rate within the first 10 min of head up tilt (HUT). We present a patient whose enlarged inferior vena cava that appears to be a contributing mechanism to her POTS and presyncopal symptoms. PMID- 22314778 TI - Olfactory dysfunction and parasympathetic dysautonomia in Parkinson's disease. AB - OBJECTIVE: Olfactory impairment occurs early in Parkinson's disease (PD), as may dysautonomia. We investigated the relationship between olfaction and dysautonomia as well as other non-motor manifestations of PD. METHODS: Olfaction [University of Pennsylvania Smell Identification Test (UPSIT)], autonomic function in the pupillary (constriction and redilation velocity) and cardiac systems (resting low and high-frequency heart rate variability (LF and HF HRV), positional changes in systolic blood pressure), neuropsychiatric function [Mini-mental Status Exam (MMSE)], Hamilton Depression Scale, activities of daily living [(ADLs), Schwab and England ADLs scale], quality of life [Short Form-36 health survey, PD Questionnaire 39 (PDQ-39)], and other non-motor symptoms [Non-motor Symptoms Scale (NMSS)] were simultaneously assessed in 33 participants (15 PD, 18 controls). Group comparisons, Spearman's coefficients and non-parametric rank based regression were employed to characterize relationships between olfaction and non-motor features. RESULTS: Smell scores were lower in the PD group and correlated positively with pupil constriction velocity and HF HRV. Smell scores were correlated negatively with PDQ-39 and gastrointestinal items of the NMSS and positively with MMSE and Schwab and England ADLs. These correlated measures were not significant terms in regression models of smell scores in which age and PD diagnosis were significant and accounted for over half of the variability (R squared 0.52-0.58). INTERPRETATION: This study suggests olfactory involvement occurs with parasympathetic dysautonomia in the pupillary and cardiovascular systems, involving both age-related and PD-related processes. Other non-motor features are concurrently involved, supporting the notion that aging and PD have widespread effects involving discrete portions of the autonomic and olfactory systems. PMID- 22314779 TI - Rodent stereotaxic surgery and animal welfare outcome improvements for behavioral neuroscience. AB - Stereotaxic surgery for the implantation of cannulae into specific brain regions has for many decades been a very successful experimental technique to investigate the effects of locally manipulated neurotransmitter and signaling pathways in awake, behaving animals. Moreover, the stereotaxic implantation of electrodes for electrophysiological stimulation and recording studies has been instrumental to our current understanding of neuroplasticity and brain networks in behaving animals. Ever-increasing knowledge about optimizing surgical techniques in rodents(1-4), public awareness concerning animal welfare issues and stringent legislation (e.g., the 2010 European Union Directive on the use of laboratory animals(5)) prompted us to refine these surgical procedures, particularly with respect to implementing new procedures for oxygen supplementation and the continuous monitoring of blood oxygenation and heart rate levels during the surgery as well as introducing a standardized protocol for post-surgical care. Our observations indicate that these modifications resulted in an increased survival rate and an improvement in the general condition of the animals after surgery (e.g. less weight loss and a more active animal). This video presentation will show the general procedures involved in this type of stereotaxic surgery with special attention to our several modifications. We will illustrate these surgical procedures in rats, but it is also possible to perform this type of surgery in mice or other small laboratory animals by using special adaptors for the stereotaxic apparatus(6). PMID- 22314780 TI - Phylogenetic characterization of a microsporidium (Nosema sp. MPr) isolated from the Pieris rapae. AB - Cabbage butterfly (Pieris rapae), included in the Lepidoptera genus, Pieris family, is the main pest that damages Cruciferae. In this paper, we reported a microsporidian isolate of Nosema species which was isolated from P. rapae in Zhenjiang City, Jiangsu Province, China. The mature spore of this microsporidium is long oval in shape and 3.8 +/- 0.3 * 2.0 +/- 0.2 MUm in size. Research results showed that the novel microsporidium cannot infect the BmN cell in vitro and silkworm larvae. The organization of rRNA gene was 5'-SSU rRNA-ITS-LSU rRNA-3'. Phylogenetic trees based on SSU rRNA and LSU rRNA gene sequences were constructed by MEGA 4.0 software. The topology showed that this microsporidium was on the same second branch of Nosema clade, and had close relationships to other Nosema species. Consequently, this microsporidium was confirmed to be a member of Nosema genus, and named as Nosema sp. MPr. PMID- 22314781 TI - The immune response to parasitic helminths of veterinary importance and its potential manipulation for future vaccine control strategies. AB - Despite the increasing knowledge of the immunobiology and epidemiology of parasitic helminths of the gastrointestinal system and the cardiorespiratory system, complications arising from infections of animals and humans with these parasites are a major clinical and economic problem. This has been attributed to the high incidence of these parasites, the widespread emergence of multi-drug resistant parasite strains and the lack of effective vaccines. Efforts to develop and produce vaccines against virtually all helminths (with the exception of Dictyocaulus viviparus and some cestode species) have been hindered by the complexity of the host-parasite relationship, and incomplete understanding of the molecular and immune regulatory pathways associated with the development of protective immunity against helminths. Novel genomic and proteomic technologies have provided opportunities for the discovery and characterisation of effector mechanisms and molecules that govern the host-parasite interactions in these two body systems. Such knowledge provided clues on how appropriate and protective responses are elicited against helminths and, thus, may lead to the development of effective therapeutic strategies. Here, we review advances in the immune response to selected helminths of animal health significance, and subsequent vaccine potential. The topics addressed are important for understanding how helminths interact with host immune defences and also are relevant for understanding the pathogenesis of diseases caused by helminths. PMID- 22314782 TI - Toxoplasma gondii invasion and replication in astrocyte primary cultures and astrocytoma cell lines: systematic review of the literature. AB - Toxoplasma gondii is a cosmopolitan protozoan which infects all homoeothermic species, including humans. This parasite may cause severe neurological problems in congenitally infected newborns or immunocompromised individuals, but it also provokes psychiatric and neurological disorders as well as behavioural and sensory deficit. There is controversy regarding the effect of T. gondii upon astrocytes, which may serve as parasite proliferation recipients or protective immune response activators within the central nervous system. This apparent contradiction could partially be due to the infection degree obtained in the different experiments reported. Thus, we decided to systematically review the in vitro models used to study these phenomena. Fifteen articles from which direct invasion and replication data could be gathered were found. Very heterogeneous results emerged, mainly due to diversity of models in relation to parasite strain (virulence), host species, parasite dose and evaluation times after infection. Also, the results were measured in diverse ways, i.e. some reported percent infected cells, while others informed parasites pervacuole or cell, or parasitic vacuoles per cell. Very few conclusions could be drawn, among them that human astrocytoma cell lines and mouse astrocytes seem more susceptible to infection and less resistant to tachyzoite proliferation than human primary culture astrocytes. The present study supports the need to reanalyse T. gondii astrocyte invasion and replication processes, especially with the use of actual technology, which allows detailed mechanistic studies. PMID- 22314783 TI - Helminth communities of two species of piscivorous birds, Ardea alba (Linnaeus) and Nyctanassa violacea (Gmelin) (Ciconiiformes: Ardeidae), in two coastal lagoons from Guerrero state, Mexico. AB - The composition and species richness in helminth communities of two species of heron, Ardea alba and Nyctanassa violacea, in two coastal lagoons from Guerrero, Mexico were examined. Nineteen species of helminth (7,804 individuals) were identified in 43 adult birds: 15 digeneans, 1 acanthocephalan, 1 cestode, and 2 nematodes. Eight species co-occurred in herons of both species and lagoons. The prevalence values of seven species and the mean abundance of five species varied significantly between species of birds and between lagoons. The heterophyid, Ascocotyle (Phagicola) longa, was the helminth numerically dominant in the helminth community of A. alba in both lagoons, while the cestode, Parvitaenia cochlearii, dominated the community of N. violacea. At the component community level, species richness varied significantly: 10 species in A. alba from Coyuca to 16 in N. violacea (Tres Palos). All of the birds examined were infected with helminth parasites: three to seven species per host in A. alba from Coyuca, and two to eight species in A. alba and N. violacea from Tres Palos. The results indicate that even though species composition was similar between both species of heron, the structure of their communities was not the same. Differences in the feeding behavior of the birds (day/night habits), as well as local differences in the abundance of species of fish, and infection levels of helminths in each lagoon are suggested as being responsible for the variations registered in the structure of the helminth communities. PMID- 22314784 TI - Evaluation of the intestinal microbial diversity in miniature pig after orally infected with Entamoeba histolytica. AB - The objective of this study was to analyze the difference in intestinal microbial diversity between healthy and (Entamoeba histolytica) orally infected minipig. Enterobacterial repetitive intergenic consensus (ERIC)-PCR was applied to analyze this diversity and dynamic change, including the duodenum, jejunum, ileum, cecum, and rectum from healthy and orally infected minipig at different time points. The results showed that the intestinal microbial community of the control minipigs was stable and the ERIC-PCR band numbers of the control minipigs were the lowest in the rectum and highest in the cecum. ERIC-PCR bands of orally inoculated minipigs showed no obvious change until 24 h after postinoculation (hpi). The numbers of the ERIC-PCR bands gradually decreased from 24 to 72 hpi, then, with the development of disease, the band numbers gradually increased until 6 days postinoculation. The prominent bacteria had changed in the presence of E. histolytica infection and the DNAstar of staple of ERIC-PCR showed that obligate aerobes and facultative aerobes (Escherichia coli, Shigella, Salmonella) became the preponderant bacilli in the intestine of orally infected minipigs with E. histolytica. This study has provided significant data to clarify the intestinal microbial diversity and dynamic change of healthy and E. histolytica orally infected minipigs. PMID- 22314785 TI - Identifying quantitative trait loci and determining closely related stalk traits for rind penetrometer resistance in a high-oil maize population. AB - Stalk lodging in maize causes annual yield losses between 5 and 20% worldwide. Many studies have indicated that maize stalk strength significantly negatively correlates with lodging observed in the field. Rind penetrometer resistance (RPR) measurements can be used to effectively evaluate maize stalk strength, but little is known about the genetic basis of this parameter. The objective of this study was to explore a genetic model and detect quantitative trait loci (QTL) of RPR and determine relationships between RPR and other stalk traits, especially cell wall chemical components. RPR is quantitative trait in nature, and both additive and non-additive effects may be important to consider for the improvement of RPR. Nine additive-effect QTLs covering nine chromosomes, except chromosome 5, and one pair of epistatic QTLs were detected for RPR. CeSA11 involved in cellulose synthesis and colorless2 involved in lignin synthesis were identified as possible candidate genes for RPR. Internode diameter (InD), fresh weight of internode (FreW), dry weight of internode (DryW), fresh weight and dry weight as well as cell wall components per unit volume significantly positively correlated with RPR. The internode water content (InW) significantly negatively correlated with RPR. Notably, these traits significantly correlated with RPR, and the QTLs of these traits co-localized with those of RPR. The corresponding results obtained from correlation analysis and QTL mapping suggested the presence of pleitropism or linkage between genes and indicated that these different approaches may be used for cross authentication of relationships between different traits. PMID- 22314791 TI - The Role of Toll-Like Receptors in Diabetes-Induced Inflammation: Implications for Vascular Complications. AB - Diabetes confers an increased risk for both microvascular and macrovascular complications. Numerous studies have reported increased levels of biomarkers of inflammation that could predispose to vascular complications. The pattern recognition receptors of the innate immune response, such as Toll-like receptors (TLRs), especially TLR2 and TLR4, have been incriminated in both atherosclerosis and insulin resistance. Studies have reported increased expression and activity of these receptors in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus. Most recently, knockout of TLR2 has been shown to attenuate the proinflammatory state of T1DM and the progression of diabetic nephropathy. The increased activity of TLRs in diabetes could be the result of a conspiracy of both endogenous and exogenous ligands. Biomediators of increased TLR2 and TLR4 activity include tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, monocyte chemoattractant protein-1, and type 1 interferons. Modulating these TLRs could be beneficial in forestalling diabetic complications given the pivotal role of inflammation in both microvascular and macrovascular complications. PMID- 22314792 TI - Interactions of iodoperfluorobenzene compounds with gold nanoparticles. AB - Understanding the interactions of small molecules with gold nanoparticles is important for controlling their surface chemistry and, hence, how they can be used in specific applications. The interaction of iodoperfluorobenzene compounds with gold nanoparticles was investigated by UV-Vis difference spectroscopy, surface enhanced Raman spectroscopy (SERS) and Synchrotron X-ray photoelectron spectroscopy (XPS). Results from UV-Vis difference spectroscopy demonstrated that iodoperfluorobenzene compounds undergo charge transfer complexation with gold nanoparticles. SERS of the small molecule-gold nanoparticle adducts provided further evidence for formation of charge transfer complexes, while Synchrotron X ray photoelectron spectroscopy provided evidence of the binding mechanism. Demonstration of interactions of iodoperfluorobenzene compounds with gold nanoparticles further expands the molecular toolbox that is available for functionalising gold nanoparticles and has significant potential for expanding the scope for generation of hybrid halogen bonded materials. PMID- 22314793 TI - Teaching medical students how to break bad news with standardized patients. AB - One of the biggest challenges that a physician will face is conveying difficult news (CDN) to a patient.The ability to provide this information may either strengthen or destroy the patient-physician relationship. Despite the importance of this skill, formal education for medical students has been limited. To improve upon skill building in the medical student experience, fourth year medical students(on their oncology clerkship) spent 3 hours partaking ina CDN session. During this session, each student had a videotaped encounter with a standardized patient, followed by a small group discussion and review of the tape with other students and a clinician. We evaluated the experience with pre- and post questionnaires assessing overall knowledge,satisfaction, and specific components of the curriculum. The objective of this study was to review our institution's educational program focused on teaching techniques for CDN. PMID- 22314794 TI - The future workforce in cancer prevention: advancing discovery, research, and technology. AB - As part of a 2-day conference on October 15 and 16, 2009, a nine-member task force composed of scientists, clinicians, educators, administrators, and students from across the USA was formed to discuss research, discovery, and technology obstacles to progress in cancer prevention and control, specifically those related to the cancer prevention workforce. This article summarizes the task force's findings on the current state of the cancer prevention workforce in this area and its needs for the future. The task force identified two types of barriers impeding the current cancer prevention workforce in research, discovery, and technology from reaching its fullest potential: (1) limited cross disciplinary research opportunities with underutilization of some disciplines is hampering discovery and research in cancer prevention, and (2) new research avenues are not being investigated because technology development and implementation are lagging. Examples of impediments and desired outcomes are provided in each of these areas. Recommended solutions to these problems are based on the goals of enhancing the current cancer prevention workforce and accelerating the pace of discovery and clinical translation. PMID- 22314795 TI - Determination of catecholamine in human serum by a fluorescent quenching method based on a water-soluble fluorescent conjugated polymer-enzyme hybrid system. AB - In this paper, a sensitive water-soluble fluorescent conjugated polymer biosensor for catecholamine (dopamine DA, adrenaline AD and norepinephrine NE) was developed. In the presence of horse radish peroxidase (HRP) and H(2)O(2), catecholamine could be oxidized and the oxidation product of catecholamine could quench the photoluminescence (PL) intensity of poly(2,5-bis(3-sulfonatopropoxy) 1,4-phenylethynylenealt-1,4-poly(phenylene ethynylene)) (PPESO(3)). The quenching PL intensity of PPESO(3) (I(0)/I) was proportional to the concentration of DA, AD and NE in the concentration ranges of 5.0 * 10(-7) to 1.4 * 10(-4), 5.0 * 10(-6) to 5.0 * 10(-4), and 5.0 * 10(-6) to 5.0 * 10(-4) mol L(-1), respectively. The detection limit for DA, AD and NE was 1.4 * 10(-7) mol L(-1), 1.0 * 10(-6) and 1.0 * 10(-6) mol L(-1), respectively. The PPESO(3)-enzyme hybrid system based on the fluorescence quenching method was successfully applied for the determination of catecholamine in human serum samples with good accuracy and satisfactory recovery. The results were in good agreement with those provided by the HPLC-MS method. PMID- 22314796 TI - Comparison of enrollees and decliners of Parkinson disease sham surgery trials. AB - Concerns have been raised that persons with serious illnesses participating in high-risk research, such as PD patients in sham surgery trials, have unrealistic expectations and are vulnerable to exploitation. A comparison of enrollees and decliners of such research may provide insights about the adequacy of decision making by potential subjects. We compared 61 enrollees and 10 decliners of two phase II neurosurgical intervention (i.e., cellular and gene transfer) trials for PD regarding their demographic and clinical status, perceptions and attitudes regarding research risks, potential direct benefit, and societal benefit, and perspectives on the various potential reasons for and against participation. In addition to bivariate analyses, a logistic regression model examined variables regarding risks and benefits as predictors of participation status. Enrollees perceived lower risk of harm while tolerating higher risk of harm and were more action oriented, but did not have more advanced disease. Both groups rated hope for benefit as a strong reason to participate, whereas the fact that the study's purpose was not solely to benefit them was rated as "not a reason" against participation. Hope for benefit and altruism were rated higher than expectation of benefit as reasons in favor of participation for both groups. Enrollees and decliners are different in their views and attitudes toward risk. Although both are attracted to research because of hopes of personal benefit, this hope is clearly distinguishable from an expectation of benefit and does not imply a failure to understand the main purpose of research. PMID- 22314797 TI - Accessory coracobrachialis: a case report with its morphological and clinical significance. AB - METHOD: During the routine dissection of a male cadaver for teaching undergraduate medical students, a variation was seen in the morphology of coracobrachialis muscle. RESULTS: The presence of an anomalous head of coracobrachialis muscle which had muscular origin from an abnormal site on coracoid process and thin tendinous insertion at the junction of brachialis and triceps muscle in common with insertion of coracobrachialis muscle to the medial surface of the middle of the shaft of the humerus. CONCLUSION: Coracobrachialis muscle can have variant origin related to its embryogenesis with its clinical and surgical significance. PMID- 22314798 TI - Quasiparticle relaxation mechanisms in superconductor/ferromagnet bilayers. AB - In this paper we review some recent results obtained on superconducting/ferromagnetic (S/F) structures when measuring the dynamic instabilities of the vortex lattice at high driving currents. The role played on the non-equilibrium properties of the hybrids by both the ferromagnetic and the superconducting materials has been analyzed with a special focus on the values and the temperature dependence of the quasiparticle relaxation times, tau(E). Knowledge of the relaxation mechanisms in these systems is extremely important in view of possible applications since it can drive the optimal choice of both materials to realize, in particular, ultrafast superconducting single photon detectors based on S/F hybrid structures. PMID- 22314799 TI - Genome-wide analysis of Aux/IAA gene family in Solanaceae species using tomato as a model. AB - Auxin plays key roles in a wide variety of plant activities, including embryo development, leaf formation, phototropism, fruit development and root initiation and development. Auxin/indoleacetic acid (Aux/IAA) genes, encoding short-lived nuclear proteins, are key regulators in the auxin transduction pathway. But how they work is still unknown. In order to conduct a systematic analysis of this gene family in Solanaceae species, a genome-wide search for the homologues of auxin response genes was carried out. Here, 26 and 27 non redundant AUX/IAAs were identified in tomato and potato, respectively. Using tomato as a model, a comprehensive overview of SlIAA gene family is presented, including the gene structures, phylogeny, chromosome locations, conserved motifs and cis-elements in promoter sequences. A phylogenetic tree generated from alignments of the predicted protein sequences of 31 OsIAAs, 29 AtIAAs, 31 ZmIAAs, and 26 SlIAAs revealed that these IAAs were clustered into three major groups and ten subgroups. Among them, seven subgroups were present in both monocot and dicot species, which indicated that the major functional diversification within the IAA family predated the monocot/dicot divergence. In contrast, group C and some other subgroups seemed to be species-specific. Quantitative real-time PCR (qRT-PCR) analysis showed that 19 of the 26 SlIAA genes could be detected in all tomato organs/tissues, however, seven of them were specifically expressed in some of tomato tissues. The transcript abundance of 17 SlIAA genes were increased within a few hours when the seedlings were treated with exogenous IAA. However, those of other six SlIAAs were decreased. The results of stress treatments showed that most SIIAA family genes responded to at least one of the three stress treatments, however, they exhibited diverse expression levels under different abiotic stress conditions in tomato seedlings. SlIAA20, SlIAA21 and SlIAA22 were not significantly influenced by stress treatments even though at least one stress related cis-element was identified in their promoter regions. In conclusion, our comparative analysis provides an insight into the evolution and expression patterns in various tissues and in response to auxin or stresses of the Aux/IAA family members in tomato, which will provide a very useful reference for cloning and functional analysis of each member of AUX/IAA gene family in Solanaceae crops. PMID- 22314800 TI - Identification of microRNA-like RNAs in a plant pathogenic fungus Sclerotinia sclerotiorum by high-throughput sequencing. AB - MicroRNAs are small non-coding RNAs of approximately 22 nt with important regulatory roles in post-transcriptional regulation of gene expression. To date, no miRNAs have been reported in plant pathogenic fungi. Here we used Solexa sequencing to find new miRNAs in a plant pathogenic fungus Sclerotinia sclerotiorum. 13,229,401 high-quality reads were obtained, a total of 5,645,718 reads were mapped to the S. sclerotiorum genome corresponding to 348,108 unique sRNAs. Among the sRNAs, 2 microRNA-like RNAs (milRNAs) and 42 mil-RNA candidates were identified by sequence analysis. Northern blot and RT-PCR results showed that some milRNAs and candidates are differentially expressed in sclerotial development suggesting the role of these milRNAs and candidates in this biological process. Our results provide new insights into the functional roles of small RNAs and add new resources for the study of plant pathogenic fungi. PMID- 22314801 TI - Diversification of three APETALA1/FRUITFULL-like genes in wheat. AB - The genomes of grass family species have three paralogs of APETALA1/FRUITFULL (AP1/FUL)-like genes (FUL1, FUL2 and FUL3) that are derived from the FUL lineage. In this study, we focus on the different roles of the wheat AP1/FUL-like genes, WFUL1 (identical to VRN1), WFUL2 and WFUL3, during the transition from vegetative to reproductive growth. Sequence analysis indicated that there was a high level of variability in the amino acid sequence of the C-domain among three WFUL genes. Expression analyses using the spring wheat cultivar Chinese Spring indicated that WFUL1/VRN1 was expressed in leaves as well as spike primordia of non-vernalized plants at the vegetative stage just before phase transition, while WFUL2 and WFUL3 were not expressed in leaves. This result indicates that WFUL1/VRN1 performs a distinct role in leaves before phase transition. In young spikes, WFUL1/VRN1 and WFUL3 were expressed in all developing Xoral organs, whereas WFUL2 expression was restricted in the Xoral organs to the lemma and palea. Furthermore, yeast two-hybrid and three-hybrid analyses revealed that WFUL2, but not WFUL1/VRN1 or WFUL3, interacted with class B and class E proteins. These results suggest that WFUL2 of wheat has class A functions in specifying the identities of Xoral meristems and outer Xoral organs (lemma and palea) through collaboration with class B and class E genes. PMID- 22314802 TI - Hydrogen bond effects in the ground and excited singlet states of 4H-1 benzopyrane-4-thione in water--theory and experiment. AB - The hydrogen bond energies for 4H-1-benzopyrane-4-thione (BPT) in its ground and two lowest excited singlet electronic states have been determined using ab initio methods. It was shown that the BPT molecule can form, as an acceptor, four relatively strong hydrogen bonds with water molecules, leading to a stable complex in the ground electronic state S(0). The hydrogen bonds involving the sulfur atom from the thiocarbonyl group were found to be stronger than those involving the oxygen atom from the benzopyran moiety. The former hydrogen bonds were predicted to become significantly weaker upon excitation to the S(1) state and, in contrast, stronger upon excitation to the S(2) state. Calculated changes in the hydrogen bond energy due to the S(0)-> S(1) and S(0)-> S(2) excitation are in very good agreement with the experimental values obtained from the absorption solvatochromic study, according to a procedure proposed by us in [E. Krystkowiak, et al., J. Photochem. Photobiol. A: Chem., 2006, 184, 250]. The maxima of absorption spectra of the BPT-water hydrogen-bonded complex, calculated taking into consideration nonspecific solute-solvent interactions, are also in good agreement with the experimental results. PMID- 22314803 TI - Multielectron-transfer reactions at single Cu(II) centers embedded in polyoxotungstates driven by photo-induced metal-to-metal charge transfer from anchored Ce(III) to framework W(VI). AB - Using carbon monoxide as a probe molecule for the oxidation state of Cu ions, we demonstrated that anchored polynuclear charge-transfer complexes consisting of Ce(III) ions and Cu(II)-substituted Keggin-type polyoxotungstates function as efficient visible-light-driven multielectron-transfer catalysts. PMID- 22314804 TI - Review of functional/anatomical imaging in oncology. AB - Patient management in oncology increasingly relies on imaging for diagnosis, response assessment, and follow-up. The clinical availability of combined functional/anatomical imaging modalities, which integrate the benefits of visualizing tumor biology with those of high-resolution structural imaging, revolutionized clinical management of oncologic patients. Conventional high resolution anatomical imaging modalities such as computed tomography (CT) and MRI excel at providing details on lesion location, size, morphology, and structural changes to adjacent tissues; however, these modalities provide little insight into tumor physiology. With the increasing focus on molecularly targeted therapies, imaging radiolabeled compounds with PET and single-photon emission tomography (SPECT) is often carried out to provide insight into a tumor's biological functions and its surrounding microenvironment. Despite their high sensitivity and specificity, PET and SPECT alone are substantially limited by low spatial resolution and inability to provide anatomical detail. Integrating SPECT or PET with a modality capable of providing these (i.e. CT or MR) maximizes their separate strengths and provides anatomical localization of physiological processes with detailed visualization of a tumor's structure. The availability of multimodality (hybrid) imaging with PET/CT, SPECT/CT, and PET/MR improves our ability to characterize lesions and affect treatment decisions and patient management. We have just begun to exploit the truly synergistic capabilities of multimodality imaging. Continued advances in the development of instrumentation and imaging agents will improve our ability to noninvasively characterize disease processes. This review will discuss the evolution of hybrid imaging technology and provide examples of its current and potential future clinical uses. PMID- 22314805 TI - Eye doses to staff in a nuclear medicine department. AB - OBJECTIVE: Occupational radiation doses to the Nuclear Medicine Department staff at Mount Vernon Hospital are routinely measured using optically stimulated luminescence dosemeters for whole-body effective dose and ring thermoluminescence dosemeters (TLDs) for finger dose. In 2002, a project was carried out using LiF:Mg,Cu,P Chinese TLDs to measure the dose to the lens of the eye received by staff during normal working procedures. METHODS: Separate pairs of TLDs were worn by staff on their forehead between their eyes while dispensing and releasing in the radiopharmacy, injecting, and when administering I-131 capsules to patients. The dose received was calculated using calibration data from identical TLDs irradiated with Tc-99m, I-131, and the Ir-192 source of a Gammamed High Dose Rate (HDR) treatment unit. Data were collected over a 5-month period and the mean dose to the eye was calculated for each procedure. RESULTS: Using a typical yearly workload, the annual dose to the eye for a single member of staff was calculated and found to be 4.5 mSv. CONCLUSION: The occupational eye dose limit was, at the time, 150 mSv; therefore, staff were well below the level (3/10th of this limit) that would have required them to be classified. However, there have been large increases in radiopharmacy production and I-131 therapies administered at Mount Vernon in subsequent years. It is therefore expected that the eye dose received by staff will have increased to be significantly higher than 4.5 mSv and will in fact be greater than 6 mSv, which is 3/10th of the proposed new dose limit and would require these staff to become classified workers. PMID- 22314806 TI - Measuring peptide translocation into large unilamellar vesicles. AB - There is an active interest in peptides that readily cross cell membranes without the assistance of cell membrane receptors(1). Many of these are referred to as cell-penetrating peptides, which are frequently noted for their potential as drug delivery vectors(1-3). Moreover, there is increasing interest in antimicrobial peptides that operate via non-membrane lytic mechanisms(4,5), particularly those that cross bacterial membranes without causing cell lysis and kill cells by interfering with intracellular processes(6,7). In fact, authors have increasingly pointed out the relationship between cell-penetrating and antimicrobial peptides(1,8). A firm understanding of the process of membrane translocation and the relationship between peptide structure and its ability to translocate requires effective, reproducible assays for translocation. Several groups have proposed methods to measure translocation into large unilamellar lipid vesicles (LUVs)(9-13). LUVs serve as useful models for bacterial and eukaryotic cell membranes and are frequently used in peptide fluorescent studies(14,15). Here, we describe our application of the method first developed by Matsuzaki and co-workers to consider antimicrobial peptides, such as magainin and buforin II(16,17). In addition to providing our protocol for this method, we also present a straightforward approach to data analysis that quantifies translocation ability using this assay. The advantages of this translocation assay compared to others are that it has the potential to provide information about the rate of membrane translocation and does not require the addition of a fluorescent label, which can alter peptide properties(18), to tryptophan containing peptides. Briefly, translocation ability into lipid vesicles is measured as a function of the Foster Resonance Energy Transfer (FRET) between native tryptophan residues and dansyl phosphatidylethanolamine when proteins are associated with the external LUV membrane (Figure 1). Cell-penetrating peptides are cleaved as they encounter uninhibited trypsin encapsulated with the LUVs, leading to disassociation from the LUV membrane and a drop in FRET signal. The drop in FRET signal observed for a translocating peptide is significantly greater than that observed for the same peptide when the LUVs contain both trypsin and trypsin inhibitor, or when a peptide that does not spontaneously cross lipid membranes is exposed to trypsin-containing LUVs. This change in fluorescence provides a direct quantification of peptide translocation over time. PMID- 22314807 TI - The crosstalk between autophagy and apoptosis: where does this lead? AB - Recent advances in the understanding of the molecular processes contributing to autophagy have provided insight into the relationship between autophagy and apoptosis. In contrast to the concept of "autophagic cell death," accumulating evidence suggests that autophagy serves a largely cytoprotective role in physiologically relevant conditions. The cytoprotective function of autophagy is mediated in many circumstances by negative modulation of apoptosis. Apoptotic signaling, in turn, serves to inhibit autophagy. While the mechanisms mediating the complex counter-regulation of apoptosis and autophagy are not yet fully understood, important points of crosstalk include the interactions between Beclin 1 and Bcl-2/Bcl-xL and between FADD and Atg5, caspase- and calpain-mediated cleavage of autophagy-related proteins, and autophagic degradation of caspases. Continued investigation of these and other means of crosstalk between apoptosis and autophagy is necessary to elucidate the mechanisms controlling the balance between survival and death both under normal conditions and in diseases including cancer. PMID- 22314808 TI - Horizontal transfer of microRNAs: molecular mechanisms and clinical applications. AB - A new class of RNA regulatory genes known as microRNAs (miRNAs) has been found to introduce a whole new layer of gene regulation in eukaryotes. The intensive studies of the past several years have demonstrated that miRNAs are not only found intracellularly, but are also detectable outside cells, including in various body fluids (e.g. serum, plasma, saliva, urine and milk). This phenomenon raises questions about the biological function of such extracellular miRNAs. Substantial amounts of extracellular miRNAs are enclosed in small membranous vesicles (e.g. exosomes, shedding vesicles and apoptotic bodies) or packaged with RNA-binding proteins (e.g. high-density lipoprotein, Argonaute 2 and nucleophosmin 1). These miRNAs may function as secreted signaling molecules to influence the recipient cell phenotypes. Furthermore, secreted extracellular miRNAs may reflect molecular changes in the cells from which they are derived and can therefore potentially serve as diagnostic indicators of disease. Several studies also point to the potential application of siRNA/miRNA delivery as a new therapeutic strategy for treating diseases. In this review, we summarize what is known about the mechanism of miRNA secretion. In addition, we describe the pathophysiological roles of secreted miRNAs and their clinical potential as diagnostic biomarkers and therapeutic drugs. We believe that miRNA transfer between cells will have a significant impact on biological research in the coming years. PMID- 22314809 TI - Genetics of pancreatitis: an update for clinicians and genetic counselors. AB - With novel genetic technologies available, there is a paradigm shift in the way that risk assessments, diagnoses,and therapies for genetic susceptibility syndromes are addressed. Hereditary pancreatitis is among these conditions, for which genetic counseling and next generation sequencing, help families better understand, cope with and live healthier lives. Identifying a genetic etiology to a condition formally believed to be solely environmentally induced can alter the path for treatment for many patients. This finding introduces the concept of gene environment interactions in human disease and the relationship between genetic predisposition and exposure risk in disease development. The genetic counseling process is complex with medical explanations, psychosocial issues relating to coping with diagnosis, potential future health problems, recurrence risks and family planning. These sometimes difficult conversations can be facilitated by a genetic counselor as a member of the multidisciplinary team. This chapter addresses the intricate medical and psychosocial issues that can arise in the setting of treating patients with hereditary pancreatitis. PMID- 22314810 TI - Is indeterminate colitis determinable? AB - About 10% of patients with colitis due to inflammatory bowel disease have indeterminate colitis. Despite newer diagnostic tools, the frequency has not diminished over the past 33 years. The current preferred term among academicians is colonic inflammatory bowel disease unclassified(IBDU), although indeterminate colitis is the term endorsed for inclusion in the ICD-10 coding system. Indeterminate colitis is more frequent among children. Theanti-Saccharomyces cerevisiae (ASCA) and perinuclear anti-cytoplasmic antibody (pANCA) are useful in distinguishing IBDU from ulcerative colitis and Crohn's disease. However, current serologic and genetic studies, as well as endoscopic and imaging studies lack sufficient positive predictive values to make a definite diagnosis of Crohn's colitis or ulcerative colitis. Patients with IBDU who undergo proctocolectomy with ileal pouch-anal anastomosis have more complications than patients with ulcerative colitis. Although some patients with indeterminate colitis eventually develop characteristic ulcerative colitis or Crohn's disease, a subgroup are durably indeterminate. PMID- 22314811 TI - Drug-induced pancreatitis. AB - Drugs are thought to be a rare cause for acute pancreatitis; however 525 different drugs are listed in the World Health Organization (WHO) database suspected to cause acute pancreatitis as a side effect. Many of them are widely used to treat highly prevalent diseases. The true incidence is not entirely clear since only few systematic population based studies exist. The majority of the available data are derived from case reports or case control studies. Furthermore, the causality for many of these drugs remains elusive and for only 31 of these 525 dugs a definite causality was established. Definite proof for causality is defined by the WHO classification if symptoms reoccur upon rechallenge.In the actual algorithm the diagnosis is confirmed if no other cause of acute pancreatitis can be detected, and the patient is taking one of the suspected drugs. PMID- 22314812 TI - Peri-conception hyperglycaemia and nephropathy are associated with risk of congenital anomaly in women with pre-existing diabetes: a population-based cohort study. AB - AIMS: The aim of this study was to quantify the risk of major congenital anomaly, and to assess the influence of peri-conception HbA(1c) and other clinical and socio-demographic factors on the risk of congenital anomaly occurrence in offspring of women with type 1 and type 2 diabetes diagnosed before pregnancy. METHODS: This was a population-based cohort study using linked data from registers of congenital anomaly and diabetes in pregnancy. A total of 401,149 singleton pregnancies (1,677 in women with diabetes) between 1996 and 2008 resulting in live birth, fetal death at >=20 weeks' gestation or termination of pregnancy for fetal anomaly were included. RESULTS: The rate of non-chromosomal major congenital anomaly in women with diabetes was 71.6 per 1,000 pregnancies (95% CI 59.6, 84.9), a relative risk of 3.8 (95% CI 3.2, 4.5) compared with women without diabetes. There was a three- to sixfold increased risk across all common anomaly groups. In a multivariate analysis, peri-conception glycaemic control (adjusted OR [aOR] 1.3 [95% CI 1.2, 1.4] per 1% [11 mmol/mol] linear increase in HbA(1c) above 6.3% [45 mmol/mol]) and pre-existing nephropathy (aOR 2.5 [95% CI 1.1, 5.3]) were significant independent predictors of congenital anomaly. Associations with gestation at booking (aOR 1.1 [95% CI 1.0, 1.1]) and parity (aOR 1.6 [95% CI 1.0, 2. 5]) were not significant. Unadjusted risk was higher for women from deprived areas or who did not take folate. Type and duration of diabetes, ethnicity, age, BMI, preconception care, smoking and fetal sex were not associated with congenital anomaly risk. CONCLUSIONS: Peri-conception glycaemia is the most important modifiable risk factor for congenital anomaly in women with diabetes. The association with nephropathy merits further study. PMID- 22314813 TI - Rapamycin toxicity in MIN6 cells and rat and human islets is mediated by the inhibition of mTOR complex 2 (mTORC2). AB - AIMS/HYPOTHESIS: Rapamycin (sirolimus) is one of the primary immunosuppressants for islet transplantation. Yet there is evidence that the long-term treatment of islet-transplant patients with rapamycin may be responsible for subsequent loss of islet graft function and viability. Therefore, the primary objective of this study was to elucidate the molecular mechanism of rapamycin toxicity in beta cells. METHODS: Experiments were performed on isolated rat and human islets of Langerhans and MIN6 cells. The effects of rapamycin and the roles of mammalian target of rapamycin complex 2 (mTORC2)/protein kinase B (PKB) on beta cell signalling, function and viability were investigated using cell viability assays, insulin ELISA assays, kinase assays, western blotting, pharmacological inhibitors, small interfering (si)RNA and through the overproduction of a constitutively active mutant of PKB. RESULTS: Rapamycin treatment of MIN6 cells and islets of Langerhans resulted in a loss of cell function and viability. Although rapamycin acutely inhibited mTOR complex 1 (mTORC1), the toxic effects of rapamycin were more closely correlated to the dissociation and inactivation of mTORC2 and the inhibition of PKB. Indeed, the overproduction of constitutively active PKB protected islets from rapamycin toxicity whereas the inhibition of PKB led to a loss of cell viability. Moreover, the selective inactivation of mTORC2 using siRNA directed towards rapamycin-insensitive companion of target of rapamycin (RICTOR), mimicked the toxic effects of chronic rapamycin treatment. CONCLUSIONS/INTERPRETATION: This report provides evidence that rapamycin toxicity is mediated by the inactivation of mTORC2 and the inhibition of PKB and thus reveals the molecular basis of rapamycin toxicity and the essential role of mTORC2 in maintaining beta cell function and survival. PMID- 22314814 TI - Subcutaneous allergen-specific immunotherapy versus topical treatment in vernal keratoconjunctivitis. AB - PURPOSE: The study evaluated the treatment of cases with vernal keratoconjunctivitis by subcutaneous allergen-specific immunotherapy (SCIT) versus topical treatment according to clinical improvement and total serum immunoglobulin (Ig) E. DESIGN: Prospective randomized study. METHODS: The study included 64 patients with bilateral vernal keratoconjunctivitis. Cases were divided into 2 groups: group 1, 32 patients who were subjected to topical treatment; and group 2, 32 patients who were subjected to intradermal skin reactions to different allergens. Prepared subcutaneous injections of different allergens were administered. Follow-up was performed to detect criteria of improvement according to clinical data and total serum IgE. RESULTS: The study revealed that the treatment by SCIT was more effective in improving the clinical symptoms and reducing the serum IgE than topical treatment because there was a greater reduction in symptoms in group 1 of immunotherapy (72%) than in group 2 of medical treatment (59%) (P < 0.05). Also, there was a significant reduction in total serum IgE (P < 0.05) in group 1 (62%) compared to group 2 (42%). However, the intradermal test for each group of patients showed that 62% of the patients were sensitive to pollens, 19% to house dust, and 19% to more than one allergen. CONCLUSIONS: Treatment of vernal keratoconjunctivitis by SCIT was more effective than topical treatment in improving the clinical symptoms and reducing the total serum IgE. PMID- 22314815 TI - Review: keratoconus in Asia. AB - Keratoconus is an ectatic corneal disorder for which exciting therapeutic and diagnostic technologies are emerging. However, its pathogenesis is still heterogeneous and elusive. We researched overlooked Asian keratoconus data by literature review of databases (PubMed, MEDLINE, Ovid, Google Scholar, Cornea, and Cochrane) using key words "keratoconus, Asia, epidemiology, treatment, risk factors, genes" and names of Asian countries. Articles and their references were analyzed. Studies showed that keratoconus may be more prevalent, have earlier onset, and have greater disease progression in certain Asian and non-Asian ethnicities, particularly Indians, Pakistanis, Middle Easterners, and Polynesians, compared with white populations. Epidemiological risk factors include ethnicity, age (younger than 30 years), gender (male), positive family history, and eye rubbing. Genetic and disease risk factors include atopy, vernal keratoconjunctivitis, Down syndrome, pellucid marginal corneal degeneration, VSX1 (visual system homeobox 1) gene, and Leber congenital amaurosis. Differentiation of heterogeneous keratoconus subsets with detailed genotype-phenotype characterization may advance understanding. Comprehensive multiethnic population studies with valid large-scale data are needed. New effective treatments (deep anterior lamellar keratoplasty, intrastromal corneal ring segments, and corneal collagen cross-linking with riboflavin) are succeeding previous treatments. PMID- 22314816 TI - Long-term follow-up of the corneal endothelium after pediatric cataract surgery. AB - PURPOSE: To evaluate the long-term effects on corneal endothelium after pediatric cataract surgery. METHODS: We conducted a cross-sectional study of 58 eyes operated for unilateral pediatric cataract with a mean age at the time of cataract surgery of 38.2 +/- 41.6 months (range, 1-171 months) and a mean follow up between cataract surgery and assessments of 149.6 +/- 69.8 months (range, 30 319 months). Parameters that were studied were endothelial cell density, hexagonal cell percentage, and coefficient of variation of cell area. Parameters in the operated eyes were compared with the normal unoperated eyes. RESULTS: Regarding the endothelial cell density (Student t test, P = 0.000), there are statistically significant differences between groups (operated and unoperated eyes), with an average loss of 9.2% in the operated eyes. With the hexagonal cell percentage (Student t test, P = 0.508) and the coefficient of variation of cell area (Wilcoxon test, P = 0.595), there was an absence of statistically significant differences between the operated and unoperated eyes. CONCLUSIONS: Endothelial cell loss was 9.2%, and no difference was found in hexagonal cell percentage and coefficient of variation of cell area between the operated and unoperated eyes 12.5 years after unilateral pediatric cataract surgery. PMID- 22314817 TI - Changes in refraction, ocular aberrations, and corneal structure after suspending rigid gas-permeable contact lens wear in keratoconus. AB - PURPOSE: This study reports on changes in visual acuity, ocular higher-order aberrations, and refraction after suspending rigid gas-permeable lens wear for 1 week in 15 patients with moderate to severe keratoconus. Alterations in the anterior surface, central corneal powers and axes, and central corneal thickness were also explored. METHODS: Scheimpflug photography and Hartmann-Shack aberrometry were performed at 2 visits, 7 days apart, after the patients had removed their habitual contact lenses. Subjective refraction and both high- and low-contrast logarithm of the minimum angle of resolution visual acuities were also recorded at both visits. RESULTS: Reductions in both high-contrast visual acuity (P = 0.001) and low-contrast visual acuity (P = 0.002), along with an increase in third-order root mean square aberrations (P = 0.008), occurred after rigid gas-permeable lens wear was suspended in these patients with keratoconus. However, no significant changes in subjective refraction were found over the 1 week period (P >= 0.10). Significant correlations were observed between third order coma root mean square aberrations and the measured high-contrast (r(p) >= 0.59; P <= 0.02) and low-contrast visual acuities (r(P) >= 0.61; P <= 0.015). In addition to increases in the anterior surface central corneal powers (P <= 0.02), a reduction in central corneal thickness also was found between the 2 visits (P = 0.00016). CONCLUSIONS: Changes in the optical and structural parameters of the keratoconic cornea occur after suspending rigid gas-permeable contact lens wear. This information may be of interest to practitioners concerned with prescribing aberration-controlling soft contact lenses for such patients. PMID- 22314818 TI - Intraoperative corneal thickness measurements during corneal collagen cross linking with hypoosmolar riboflavin solution in thin corneas. AB - PURPOSE: To monitor corneal thickness during the corneal collagen cross-linking procedure in corneal ectatic diseases, by using isoosmolar riboflavin solution with 20% dextran and hypoosmolar riboflavin solution without dextran. METHODS: The corneal thickness measurements were obtained at 5 different time points: after epithelial removal, after isotonic riboflavin solution application for 30 minutes, after hypotonic riboflavin solution application for 10 minutes, and after 10 and 30 minutes of isotonic riboflavin solution application. RESULTS: A total of 9 eyes of 9 patients with progressive keratoconus (n = 8) and pellucid marginal degeneration (n = 1) were included in this study. After epithelial debridement, the thinnest pachymetric readings were between 331 and 399 MUm (average, 376.11 +/- 19.88 MUm). The thinnest pachymetric measurements decreased significantly after the application of isoosmolar riboflavin solution for 30 minutes (by 55.22 +/- 13.40 MUm) and increased significantly after hypoosmolar riboflavin application for 10 minutes (by 59.56 +/- 29.71 MUm) (P < 0.01 for both). This artificial swelling effect was transient, and the thinnest pachymetric readings decreased significantly after 10 and 30 minutes of isoosmolar riboflavin application compared with thickness at the end of hypoosmolar riboflavin application (by 50.22 +/- 29.68 MUm and 65.11 +/- 27.94 MUm, respectively) (P < 0.01 for both). CONCLUSIONS: The iatrogenic swelling effect of the hypoosmolar riboflavin solution might be short acting and not durable throughout the UVA application in collagen cross-linking procedure. PMID- 22314819 TI - Corneal biomechanical changes after intracorneal ring segment implantation in keratoconus. AB - PURPOSE: To evaluate by means of the Ocular Response Analyzer (ORA) the biomechanical changes that follow intracorneal ring segment (ICRS) implantation and to develop a predicting model for the postoperative visual outcome, considering these biomechanical changes and other clinical parameters. METHODS: A total of 45 consecutive keratoconic eyes of 35 patients aged 18 to 55 years and implanted with ICRS were included in this retrospective study. All patients were implanted with KeraRing using femtosecond laser technology. Visual acuity, refraction, corneal topography, and aberrations were evaluated during a 6-month follow-up. Additionally, corneal biomechanical changes were evaluated with the ORA system. RESULTS: No significant changes in corneal hysteresis (CH) and corneal resistance factor (CRF) were observed at 1 month postoperatively (P >= 0.39). However, significant changes in these parameters were detected afterward (CH, 3 months, P = 0.03; CRF, 6 months, P = 0.02). Preoperative corneal biomechanical parameters were significantly correlated with postoperative corneal higher-order aberrations at all visits (P <= 0.05), although these correlations became stronger at the end of the follow-up. Multiple regression analysis revealed that corrected distance visual acuity at 1 month after surgery was significantly correlated with the preoperative mean keratometry and the preoperative difference between CH and CRF (P < 0.01, adjusted R2 of 0.66). CONCLUSIONS: Biomechanical parameters measured with the ORA and mean keratometry are factors allowing a prediction of the postoperative visual outcome in a short term after ICRS implantation in keratoconic eyes. In the long term, corneal biomechanical changes limit the prediction of the ring segment effect. PMID- 22314820 TI - The New Zealand National Eye Bank study: trends in the acquisition and storage of corneal tissue over the decade 2000 to 2009. AB - PURPOSE: To evaluate trends in the acquisition, storage, and utilization of donated corneal tissue in New Zealand, 2000 to 2009. METHODS: The New Zealand National Eye Bank records were analyzed for the decade January 2000 to December 2009. Variables analyzed included donor demographics (age, sex, and ethnicity), donor source, donor cause of death, death-to-preservation interval (DPI), corneal storage time, tissue contamination, endothelial assessment, cornea suitability for transplantation, and corneal tissue utilization. RESULTS: A total of 1268 eye donors were identified during the 10-year period. Overall, 36% (n = 457) were female and 64% male (n = 813). Median donor age was 67 years, and 23% of donors were younger than 50 years (range, 5-90 years). There was a decrease in donor age over the decade (P = 0.006). The median DPI was 18.5 hours. No relationship was identified between cornea suitability for transplantation and DPI (P = 0.28) or donor gender (P = 0.54). There was a low microbial contamination rate (1%). Human immunodeficiency virus, hepatitis B, or hepatitis C serology was positive in 48 donors (4%). Overall, 90% of corneas were suitable for transplantation with a high utilization rate (88%). A novel association was identified between male sex and lower corneal endothelial cell density (P = 0.03). CONCLUSIONS: This New Zealand National Eye Bank analysis identified trends in the acquisition, storage, and utilization of donated corneal tissue throughout New Zealand over the past decade and provides valuable additional information to the international eye bank data. PMID- 22314821 TI - Anterior segment optical coherence tomography features of acute corneal hydrops. AB - PURPOSE: To describe the clinical significance of in vivo corneal findings in eyes with acute corneal hydrops. METHODS: Medical records and anterior segment optical coherence tomography (ASOCT) images of 24 patients with keratoconus and unilateral acute corneal hydrops were reviewed. Clinical findings and position, integrity, and orientation of the Descemet membrane (DM) on ASOCT were noted. Size of the DM break, depth of the DM detachment, and corneal thickness were measured by ASOCT and correlated with the duration of corneal edema, assessed clinically. Outcomes of intracameral perfluoropropane (C(3)F(8)) gas in 13 eyes and histopathological findings after penetrating keratoplasty in 2 eyes were also correlated with serial ASOCT findings. RESULTS: Duration of corneal edema was 9.3 +/- 4.4 weeks. On ASOCT, DM showed 3 patterns: detachment with break and rolled ends (n = 13), detachment with break and flat ends (n = 10), and detachment with no break (n = 1). Initial corneal thickness was 1.3 +/- 0.25 mm, size of the DM break was 1.1 +/- 0.8 mm, and depth of the DM detachment was 0.9 +/- 0.6 mm. On multiple regression analysis, duration of corneal edema showed significant positive association with the depth of DM detachment (P = 0.0002) and size of DM break (P = 0.002) and negative association with intracameral C3F8 (P < 0.0001). Correlation of ASOCT with histopathological findings revealed 2 stages of resolution of hydrops: reattachment of DM and endothelial migration. CONCLUSIONS: Eyes with deeper DM detachments and larger DM breaks required more time for resolution of corneal edema despite intracameral C(3)F(8). This association needs to be validated by a prospective study. PMID- 22314822 TI - Surgical reduction of ocular pigmentation in patients with oculodermal melanocytosis. AB - PURPOSE: To show the outcomes of surgical reduction of ocular pigmentation in patients with oculodermal melanocytosis. METHODS: Surgical reduction of ocular pigmentation was performed in 49 patients with oculodermal melanocytosis at the Asan Medical Center, Seoul, Republic of Korea, between January 2005 and January 2009. RESULTS: In all patients, ocular pigmentation was cosmetically reduced, and most patients were satisfied with the results of surgery. Preoperative and postoperative visual acuities, intraocular pressure (IOP), keratometry, and refractive outcomes did not differ significantly. During the follow-ups, 14 patients showed transient IOP elevation and 4 patients showed conjunctival neovascularization. CONCLUSIONS: Surgical reduction of oculodermal melanocytosis seemed to be cosmetically satisfactory and did not cause significant changes in visual acuity, refraction, or keratometry, although 28.6% (14 of 49) of patients showed transient IOP elevation. PMID- 22314823 TI - Characterization of glutathione uptake, synthesis, and efflux pathways in the epithelium and endothelium of the rat cornea. AB - PURPOSE: To compare and contrast glutathione (GSH) uptake, synthesis, and efflux pathways in the epithelium and endothelium of the rat cornea. METHODS: Whole eyes were cryosectioned in an equatorial orientation and sections fixed in either 0.75% paraformaldehyde alone or 0.75% paraformaldehyde plus 0.01% glutaraldehyde. Sections were then labeled with GSH, gamma-glutamylcysteine synthetase (gamma GCS), cysteine, xCT, or multidrug resistance-associated proteins (MRP1, 2, 4, and 5 isoforms) antibodies and then with secondary antibodies to visualize labeling patterns. Cornea morphology was visualized using propidium iodide. Reverse transcriptase-polymerase chain reaction was used to determine which of the 3 putative GSH transporters, NaDC3, C-terminal organic anion transporter 1 (OAT1), and/or N-terminal organic anion transporter 3 (OAT3), were present at the transcript level in the cornea. Colocalization of OAT3 and sodium dependent dicarboxylate transporter 3 (NaDC3) was performed by labeling with OAT3 and NaDC3 primary antibodies that were visualized with secondary antibodies and then mounted in 4'6-diamidino-2-phenylindole to visualize cell morphology. RESULTS: Although immunohistochemical labeling showed GSH to be localized throughout the cornea, labeling for cysteine, gamma-GCS, xCT, MRP4, and MRP5 was strongest in the epithelium. In contrast, although GSH labeling was strong in the endothelium, xCT and MRP labeling was absent and cysteine and gamma-GCS labeling was weak relative to the epithelium. Reverse transcriptase-polymerase chain reaction revealed OAT3 and NaDC3, but not OAT1, to be present at the transcript level. Immunohistochemical labeling showed OAT3 and NaDC3 to be localized to the endothelium but absent from the epithelium. CONCLUSIONS: The corneal epithelium and endothelium exhibit differences in GSH uptake, synthesis, and efflux pathways. The corneal epithelium seems to be the region where GSH synthesis and GSH efflux occurs. However, in the endothelium, GSH accumulation is likely to be predominantly by direct uptake of GSH from the aqueous humor. PMID- 22314824 TI - Management of intraepithelial and invasive neoplasia of the cornea and conjunctiva. PMID- 22314825 TI - Infectious endophthalmitis after Boston type 1 keratoprosthesis implantation. AB - PURPOSE: To determine the incidence, clinical features, and outcomes of infectious endophthalmitis after Boston Type 1 Keratoprosthesis (KPro) implantation. METHODS: Retrospective, consecutive case series. Chart review of 105 patients (126 eyes) who had KPro implantation at Cincinnati Eye Institute between November 2004 and November 2010 and who were followed up for at least 1 month (range, 1 month to 66 months; mean 25 months) revealed 3 cases who developed infectious endophthalmitis. RESULTS: One patient had a history of congenital glaucoma, and 2 patients had Stevens-Johnson syndrome. Two had KPro implantation for penetrating keratoplasty failure and 1 had necrosis of a previous KPro cornea. The incidence of endophthalmitis was 2.4%. All patients wore a contact lens and were on vancomycin and a fourth-generation fluoroquinolone (moxifloxacin). Vitreous fluid cultures yielded Ochrobactrum anthropi, Candida parapsilosis, and Candida albicans. All patients received intravitreal amphotericin, vancomycin, and/or ceftazidime. Topical and oral antiinfective agents were tailored based on sensitivities. One patient required KPro removal and therapeutic penetrating keratoplasty. Vision did not recover for 2 patients who presented with vision decreased to light perception. One patient, who presented with decreased vision of 20/400, recovered to 20/60. CONCLUSIONS: Infectious endophthalmitis is a devastating complication that can occur after Boston KPro implantation even with prophylactic vancomycin, a fourth-generation fluoroquinolone, and a therapeutic contact lens. Fungal and gram-negative organisms are a growing cause for concern. Further study is needed on optimal prophylaxis regimens, including the use of antifungals, especially for high-risk eyes, such as those with autoimmune cicatrizing disease. PMID- 22314826 TI - Human glioblastoma cells display mesenchymal stem cell features and form intracranial tumors in immunocompetent rats. AB - Isolation of highly tumorigenic stem-like cells from human glioblastoma specimens and cell lines has been focusing on their neural stem cells properties or capacity to efflux fluorescent dyes. Here, we report that, under standard culture conditions, human glioblastoma cells of the U87MG cell line display a predominant mesenchymal phenotype and share some of the in vitro properties of mesenchymal stem cells. Moreover, these cells were capable of forming tumors in immunocompetent rats. Infiltrative intracranial tumors could be detected 15 to 30 days post-stereotaxic cell injection within the motor cortex. Tumors were comprised by pleomorphic and mitotically active cells and displayed necrotic and hemorrhagic foci, which are common features of human glioblastomas. This rather unexpected in vivo tumorigenesis in the absence of immune suppression more closely mimics the physiological milieu encountered by tumor cells and could be explored as a xenograft orthotopic model of human glioblastomas to address new therapeutic approaches, particularly those involving immune effector mechanisms. PMID- 22314827 TI - Visualization of the hematopoietic microenvironment: an alternative approach using the dorsal skinfold chamber model. PMID- 22314828 TI - Effects of inorganic arsenic on bone marrow hematopoietic cells: an emphasis on apoptosis and Sca-1/c-Kit positive population. AB - Apoptosis, proliferation and differentiation are balanced molecular processes which may alter their pattern during environmental insults. Arsenic is an environmental pollutant, ranks 20(th) in abundance in the earth crust, 14(th) in sea water and 12(th) in the human body. Millions of people worldwide are chronically exposed to arsenic often due to naturally occurring arsenic in ground water. Hematopoietic stem cells within the bone marrow are the source of all haematopoietic cell lineages and are essential for tissue development throughout the life. In this experimental study, we have evaluated the impact of arsenic, on blood and blood forming cells by the changes in their cellular morphology, immune functional capacity, alteration of bone marrow CD34 positive stem/progenitors and changes in the phenotype of Sca-1, c-Kit dual positive primitive stem cell population. The study revealed that arsenic has a significant effect on bone marrow and hematopoietic stem cells, their immune capacity and upregulation of death process, all indicative of impairment in differentiation suggesting presence of deregulation in their precursors by arsenic toxicity. PMID- 22314829 TI - Potential yoga modules for treatment of hematopoietic inhibition in HIV-1 infection. AB - This article is expected to contribute towards understanding the therapeutic benefits of specific yoga modules on the inhibition of replication and enhancement to normal levels of hematopoiesis in HIV-1 infected subjects. More unique could be the effects of yoga on the indirect effects of HIV-1 induced hematopoietic inhibition of the CD34+ progenitor stem cells, via the CD4+ T lymphocytes. Such indirect effects may be caused by host cellular factors. Yoga practices may also improve the self renewal capacity (a step that precedes commitment of CD34+ progenitor cells to terminal differentiation), via STAT5 gene regulation. This may eliminate the need for constitutive STAT5 gene expression through gene therapy. In this article recent research and ancient Indian literature are reviewed to devise yoga modules for the potential treatment of hematopoietic inhibition in HIV-1 infection. The possible mechanisms through which hematopoietic inhibition may occur in HIV-1 infected patients are first described followed by the role of stress in the progression of HIV where probable involvement of psycho-neuro-immunological axis (PNI) is highlighted. Yoga therapy is introduced and its effectiveness in terms of evidence in relevant area is reviewed. Further, the basic principles of Integrated Approach of Yoga Therapy [IAYT] are described and depending on the potential mechanisms through which yoga therapy may act, both modern scientific research and ancient "scriptural" evidence are provided at all the five levels of existence (body, life force, emotional, intellectual and bliss). This will enable to design comprehensive yoga modules that may intervene in this indirect inhibition of haematopoiesis in HIV-1 infected individuals and potentially restore normal levels of haematopoiesis. PMID- 22314830 TI - Photocatalytic synthesis of pure and water-dispersible graphene monosheets. PMID- 22314831 TI - Analysis of gene expression and gene silencing in human macrophages. AB - This unit describes how to execute a gene expression study with human macrophages. It includes protocols for human macrophage preparation, RNA extraction, real-time PCR analysis, and microarray analysis. The unit also includes a protocol for gene silencing in human macrophages. Altering gene expression can be useful to study the contribution of the gene to macrophage function or even expression of other genes. PMID- 22314832 TI - Mouse models of atherosclerosis. AB - Genetically altered mice carrying mutations of genes encoding crucial components of the immune system and lipid metabolism have been widely used to study the role of immune responses and inflammation in atherosclerosis. These mice are often fed a diet, with a high content of cholesterol and saturated fat in order to induce hypercholesterolemia and arterial lesions. We review the different mouse models of atherosclerosis, type of diets, and techniques to measure lipid deposition and lesion size in the arterial walls. Moreover, the methods used to determine the presence of the immune cells in atherosclerotic lesions are also described here. PMID- 22314833 TI - Animal models for Toxoplasma gondii infection. AB - Toxoplasma gondii is a protozoan of worldwide distribution. This unit describes murine models of acute T. gondii infection, toxoplasmic encephalitis, and Toxoplasma retinochoroiditis. T. gondii infection in SCID mice allows the study of T cell-independent mechanisms of defense. The uracil auxotroph strain cps1-1 and temperature-sensitive mutant strains of T. gondii allow studies of immunization and adoptive transfer. In vivo study of parasite host-interaction is possible with the use of parasites that express fluorescent proteins and model antigens, plus the use of transgenic mice that express the appropriate T cell receptor and fluorescently labeled leukocytes. Parasites that express bioluminescent markers make it possible to study the dynamics of infection in real time using bioluminescence imaging. Support protocols present methodology for evaluation of progression of infection and immune response to the parasite, the maintenance of T. gondii tissue cysts and tachyzoites, as well as preparation of T. gondii lysate antigens. PMID- 22314834 TI - Single-cell phospho-protein analysis by flow cytometry. AB - This protocol describes methods for monitoring intracellular phosphorylation dependent signaling events on a single-cell basis. This approach measures cell signaling by treating cells with exogenous stimuli, fixing cells with formaldehyde, permeabilizing with methanol, and then staining with phospho specific antibodies. Thus, cell signaling states can be determined as a measure of how cells interact with their environment. This method has applications in clinical research as well as mechanistic studies of basic biology. In clinical research, diagnostic or drug efficacy information can be retrieved by discovering how a disease affects the ability of cells to respond to growth factors. Basic scientists can use this technique to analyze signaling events in cell lines and human or murine primary cells, including rare populations, like B1 cells or stem cells. This technique has broad applications bringing standard biochemical analysis into primary cells in order to garner valuable information about signaling events in physiologic settings. PMID- 22314835 TI - Magnetite (Fe3O4): a new variant of relaxor multiferroic? AB - The electric polarization, dielectric permittivity, magnetoelectric effect, heat capacity, magnetization and ac susceptibility of magnetite films and polycrystals were investigated. The electric polarization of magnetite films with saturation values between 4 and 8 MUC cm(-2) was found to vanish between 32 and 38 K, but in polycrystals no phase transition was detected in this range by heat capacity. Both types of samples showed magnetoelectric effects at low temperatures below a frequency-dependent crossover. This is interpreted as arising from multiferroic relaxor behavior. PMID- 22314836 TI - Using tendon inherent electric properties to consistently track induced mechanical strain. AB - The present work explores the possibility that the inherent electrical properties of a tendon might allow it to act as its own strain gauge. Tendon has been shown to exhibit piezoelectric effects as well as streaming potentials when subjected to a mechanical stress. To assess the feasibility of using these properties to repeatably measure in situ strain,bovine Achilles tendon test specimens were connected in series with a control resistor in a direct current circuit. Longitudinal(along the collagen fiber direction) and transverse test specimens were subjected to sinusoidal tension while electrical resistance data for the specimens was collected. Change in resistance per unit strain and gauge factors (GFs) revealed a repeatable and significantly different correlation between resistance and strain for the longitudinal and transverse specimens (p<0.001). Change in resistance per unit strain values for longitudinal and transverse specimens were 0.85 and 1.76 MX/e, respectively while corresponding GFs were 0.52 and 0.74, respectively. Others have reported piezoelectric mechanisms and streaming potential mechanisms in hydrated collagen, however the present work is unique in presenting an accurate and repeatable model of anisotropic tendon behavior that could be used to develop an in situ strain sensor. PMID- 22314838 TI - Modeling the electromobility of type-I collagen molecules in the electrochemical fabrication of dense and aligned tissue constructs. AB - Isoelectric focusing (IEF) of type-I collagen molecules is a technology with proven efficacy to produce dense and aligned collagen-based biomaterials. The forces and mechanisms during IEF of collagen molecules in carrier ampholyte-free environments remain unknown. This study presents theoretical framework describing the congregation of collagen molecules along the isoelectric point (pI). A single molecule was modeled as a rod-like particle, distributed homogeneously between parallel electrodes. Upon application of electrical current, molecules migrated to the pI. The results showed that self-aggregation of collagen molecules along the pI occurred due to formation of a non-linear pH gradient that rendered the anodic side acidic, and the cathodic side basic. This pH profile and the amphoteric nature of collagen resulted in positively charged molecules at the anode and negatively charged molecules at the cathode. Therefore, repulsive electrostatic forces aided self-aggregation of molecules along the pI. The model could effectively validate the pI of collagen, the pI location, and predict that the instantaneous velocity acting on a molecule at the anode was higher than those velocities at the cathode. This fundamental information represents the baseline theory upon which we can expand our knowledge to the production of biomaterials to engineer soft tissues. PMID- 22314837 TI - Multi-scale structural and tensile mechanical response of annulus fibrosus to osmotic loading. AB - This study investigates differential multi-scale structure and function relationships of the outer and inner annulus fibrosus (AF) to osmotic swelling in different buffer solutions by quantifying tensile mechanics, glycoasamino glycan(GAG) content, water content and tissue swelling, and collagen fibril ultrastructure. In the outer AF, the tensile modulus decreased by over 70% with 0.15 M PBS treatment but was unchanged with 2 M PBS treatment. Moreover, the modulus loss following 0.15 M PBS treatment was reversed when followed by 2 M PBS treatment, potentially from increased interfibrillar and interlamellar shearing associated with fibril swelling. In contrast, the inner AF tensile modulus was unchanged by 0.15 M PBS treatment and increased following 2 M treatment. Transmission electron microscopy revealed that the mean collagen fibril diameters of the untreated outer and inner AF were 87.8 +/- 27.9 and 71.0 +/- 26.9 nm, respectively. In the outer AF, collagen fibril swelling was observed with both 0.15 M and 2 M PBS treatments, but inherently low GAG content remained unchanged. In the inner AF, 2 M PBS treatment caused fibril swelling and GAG loss, suggesting that GAG plays a role in maintaining the structure of collagen fibrils leading to modulation of the native tissue mechanical properties. These results demonstrate important regional variations in structure and composition, and their influence on the heterogeneous mechanics of the AF. Moreover, because the composition and structure is altered as a consequence of progressive disk degeneration, quantification of these interactions is critical for study of the AF pathogenesis of degeneration and tissue engineering PMID- 22314839 TI - Study on the effect of IRE1a on cell growth and apoptosis via modulation PLK1 in ER stress response. AB - The mammalian unfolded protein response (UPR) protects the cell against the stress of misfolded proteins in the endoplasmic reticulum (ER). Failure to adapt to ER stress causes the UPR to trigger apoptosis. Inositol-requiring enzyme-1a (IRE1a), as one of three unfolded protein sensors in UPR signaling pathways, senses ER unfolded proteins through an ER lumenal domain that becomes oligomerized during ER stress. It is known to be important for ER stress-mediated apoptosis and cell growth, but the exact molecular mechanism underlying these processes remains unexplored. In this study, we report that knockdown of IRE1a by an siRNA silencing approach enhanced, whereas its overexpression inhibited, cell proliferation in Hepatoma cells. Besides, overexpression of IRE1a induced, while its repression inhibited, ER stress-mediated apoptosis in Hepatomas cells. Furthermore, we found that overexpressed IRE1a can down-regulate Polo-like kinase 1(PLK1) from mRNA and protein two levels. IRE1a-mediated induction of apoptosis and inhibition of proliferation in response to ER stress is through downregulation PLK1, an early trigger for G2/M transition known to be participated in regulating cell proliferation and cell apoptosis. Collectively, these findings reveal a novel critical role of IRE1a in ER stress-mediated apoptosis and the molecular mechanisms involved. IRE1a may be a useful molecular target for the development of novel predictive and therapeutic strategies in cancer. PMID- 22314840 TI - Metabolism of peptide reporters in cell lysates and single cells. AB - The stability of an Abl kinase substrate peptide in a cytosolic lysate and in single cells was characterized. In the cytosolic lysate, the starting peptide was metabolized at an average initial rate of 1.7 +/- 0.3 zmol pg(-1) s(-1) with a t(1/2) of 1.3 min. Five different fragments formed over time; however, a dominant cleavage site was identified. Multiple rational design cycles were utilized to develop a lead peptide with a phenylalanine and alanine replaced by an (N methyl)phenylalanine and isoleucine, respectively, to attain cytosolic peptidase resistance while maintaining Abl substrate efficacy. This lead peptide possessed a 15-fold greater lifetime in the cytosolic lysate while attaining a 7-fold improvement in k(cat) as an Abl kinase substrate compared to the starting peptide. However, when loaded into single cells, the starting peptide and lead peptide possessed nearly identical degradation rates and an altered pattern of fragmentation relative to that in cell lysates. Preferential accumulation of a fragment with cleavage at an Ala-Ala bond in single cells suggested that dissimilar peptidases act on the peptides in the lysate versus single cells. A design strategy for peptide stabilization, analogous to that demonstrated for the lysate, should be effective for stabilization in single cells. PMID- 22314841 TI - Hepatocellular carcinoma in cirrhotic liver with graft-versus-host disease. PMID- 22314842 TI - Generalized lymph node immunoglobulin G amyloidoma. PMID- 22314843 TI - A comparison of bortezomib, cyclophosphamide, and dexamethasone (Vel-CD) chemotherapy without and with thalidomide (Vel-CTD) for the treatment of relapsed or refractory multiple myeloma. AB - We compared the clinical responses and toxicities between bortezomib-based salvage chemotherapy combined with cyclophosphamide, thalidomide, and dexamethasone(Vel-CTD) and without thalidomide (Vel-CD) in patients with relapsed or refractory MM. Eighty-six patients received at least two cycles of treatment with Vel-CTD (bortezomib 1.3 mg/m2 i.v. on days 1, 4, 8, and 11; cyclophosphamide 150 mg/m2 orally on days 1-4; thalidomide 50-100 mg/day orally every day; and dexamethasone 20 mg/m2 i.v. on days 1, 4, 8, and 11 every 3 weeks), and 67 patients were given at least two cycles of Vel-CD, which is the same regimen as Vel-CTD except without thalidomide. The overall response rates of the Vel-CD and Vel-CTD groups were 88% and 90% (p>0.05), respectively. There was no difference in the progression free survival (p = 0.69) and overall survival rates(p = 0.49) between the two groups. Grade 3 or more adverse hematologic events occurred in the same proportion of patients in both groups. In terms of non-hematologic toxicities, the Vel-CTD group showed a higher proportion of autonomic neuropathy, motor neuropathy, and sensory neuropathy compared to the Vel-CD group (each, p<0.05). Only three patients in the Vel-CTD group showed thrombotic events despite aspirin prophylaxis. The Vel-CD regimen inpatients with relapsed or refractory MM is an effective and more tolerable salvage therapy compared to Vel CTD in terms of its comparable response rate and less severe of non-hematologic toxicities. PMID- 22314844 TI - Dynamic structures of aqueous oxalate and the effects of counterions seen by 2D IR. AB - Two dimensional vibrational echo spectra of oxalate in the carboxylate asymmetric stretch region in D(2)O show two transitions having anomalously slow spectral diffusion and a third transition having relaxation properties typical of the free carboxylate ion. Quantitative analysis of the frequency shifts of the carboxylate asymmetric stretch modes caused by a singly charged cation in the oxalate hydration shell supports that ion pairs can be responsible for these new transitions. Experimental evidence and DFT calculations are consistent with oxalate forming a mixture of "side-on" and "end on" contact ion pairs wherein the carboxylate groups are protected from mobile heavy water molecules. PMID- 22314845 TI - Coordination of spermatogenic processes in the testis: lessons from cystic spermatogenesis. AB - A common observation in the vertebrate testis is that new germ cell clones enter spermatogenesis proper before previously formed clones have completed their development. The extent to which the developmental advance of any given germ cell clone in any phase of spermatogenesis is dependent on that of neighboring clones and/or on the coordinating influence of associated Sertoli cells in the immediate vicinity or of others further away remains unclear. This review presents an overall synthesis of findings in an ancient vertebrate, the spiny dogfish shark and shows that, even at this phyletic level, the developmental advance of a given germ cell clone is the outcome of various processes emanating from its spatiotemporal relationship with (1) its own complement of Sertoli cells in the anatomically distinct spermatocyst and (2) Sertoli cells associated with other germ cell clones that lie upstream or downstream in the spermatogenic progression and that secrete, among others, androgen and estrogen destined for target sites upstream. Analysis of the protracted spermatogenic cycle shows the coordination in space and time of spermatogenic and steroidogenic events. Furthermore, the natural withdrawal of pituitary gonadotropin support in the dogfish causes a distinct and highly ordered gradient of apoptosis among the spermatogonial generations; this in turn is a major contributing factor to the cyclic nature of sperm production observed in this lower vertebrate. Because of the simplicity of their testicular organization, their cystic spermatogenesis and their phylogenetic position, cartilaginous fishes constitute a valid vertebrate reference system for comparative analysis with higher vertebrates. PMID- 22314846 TI - Expression patterns of anoctamin 1 and anoctamin 2 chloride channels in the mammalian nose. AB - Calcium-activated chloride channels are expressed in chemosensory neurons of the nose and contribute to secretory processes and sensory signal transduction. These channels are thought to be members of the family of anoctamins (alternative name: TMEM16 proteins), which are opened by micromolar concentrations of intracellular Ca(2+). Two family members,ANO 1 (TMEM16A) and ANO 2 (TMEM16B), are expressed in the various sensory and respiratory tissues of the nose.We have examined the tissue specificity and sub-cellular localization of these channels in the nasal respiratory epithelium and in the five chemosensory organs of the nose: the main olfactory epithelium, the septal organ of Masera, the vomeronasal organ, the Grueneberg ganglion and the trigeminal system. We have found that the two channels show mutually exclusive expression patterns. ANO 1 is present in the apical membranes of various secretory epithelia in which it is co-localized with the water channel aquaporin 5. It has also been detected in acinar cells and duct cells of subepithelial glands and in the supporting cells of sensory epithelia. In contrast, ANO 2 expression is restricted to chemosensory neurons in which it has been detected in microvillar and ciliary surface structures. The different expression patterns of ANO 1 and ANO 2 have been observed in the olfactory, vomeronasal and respiratory epithelia. No expression has been detected in the Grueneberg ganglion or trigeminal sensory fibers. On the basis of this differential expression, we derive the main functional features of ANO 1 and ANO 2 chloride channels in the nose and suggest their significance for nasal physiology. PMID- 22314847 TI - Autophagy and apoptosis interplay during follicular atresia in fish ovary: a morphological and immunocytochemical study. AB - Follicular atresia in fish ovary provides an interesting model for studying autophagy and apoptosis. In order to improve knowledge of the mechanisms regulating ovarian regression, we investigated the immunolocalisation of various proteins involved in the complex network of autophagy and apoptosis. Females of three species of freshwater fish maintained in captivity were sampled after the reproductive period and the main events of follicular atresia were assessed by histology: splits in the zona radiata, yolk degradation and reabsorption, hypertrophy of the follicular cells, accumulation of autophagic vacuoles, closing of the follicular lumen and thickening of the theca. The interplay of apoptosis and autophagy was analysed by TUNEL in situ and by immunocytochemistry for caspase-3, bax, bcl-2, beclin-1 and cathepsin-D. During early and advanced stages of follicular regression, the actin cytoskeleton was well developed and labelling for bcl-2 and cathepsin-D were pronounced in the follicular cells at a stage when they were intensively involved in yolk phagocytosis. Immunofluorescence for beclin-1 was prevalent in the follicular cells, punctate labelling often surrounding autophagic vacuoles during the advanced stage of follicular regression, a critical step towards cell death. TUNEL-positive reaction and immunostaining for bax and caspase-3 demonstrated the participation of apoptosis in late follicular regression. Overall, this study provides evidence that autophagic and apoptotic proteins are activated in a coordinated fashion depending on the stage of follicular regression, with interplay between autophagy and apoptosis being essential in determining the fate of the cell during follicular atresia in fish ovary. PMID- 22314848 TI - Feasibility study of exploring a T1-weighted dynamic contrast-enhanced MR approach for brain perfusion imaging. AB - PURPOSE: To investigate the feasibility of T(1) -weighted dynamic contrast enhanced (DCE) MRI for the measurement of brain perfusion. MATERIALS AND METHODS: Dynamic imaging was performed on a 3.0 Tesla (T) MR scanner by using a rapid spoiled-GRE protocol. T(1) measurement with driven equilibrium single pulse observation of T(1) (DESPOT1) was used to convert the MR signal to tracer concentration. Cerebral perfusion maps were obtained by using an improved gamma variate model in 10 subjects and compared with those with arterial spin label (ASL) approach. RESULTS: The cerebral blood volume (CBV) values were calculated as 4.74 +/- 1.09 and 2.29 +/- 0.58 mL/100 g in gray matter (GM) and whiter matter (WM), respectively. Mean transit time (MTT) values were 6.15 +/- 0.59 s in GM and 6.96 +/- 0.79 s in WM. The DCE values for GM/WM cerebral blood flow (CBF) were measured as 53.41 +/- 9.23 / 25.78 +/- 8.91 mL/100 g/min, versus ASL values of 49.05 +/- 10.81 / 23.00 +/- 5.89 mL/100 g/min for GW/WM. Bland-Altman plot revealed a small difference of CBF between two approaches (mean bias = 3.83 mL/100 g/min, SD = 11.29). There were 6 pairs of samples (5%, 6/120) beyond the 95% limits of agreement. The correlation plots showed that the slop of Y (CBF_(_DCE)) versus X intercept (CBF_(_ASL)) is 0.95 with the intercept of 4.53 mL/100 g/min (r = 0.74; P < 0.05). CONCLUSION: It is feasible to evaluate the cerebral perfusion by using T(1)-weighted DCE-MRI with the improved kinetic model. PMID- 22314849 TI - A turn-on fluorogenic probe for detection of MDMA from ecstasy tablets. AB - We report a fluorogenic probe that is able to discriminate a range of primary or secondary biogenic amines and their natural or synthetic mimics, in water or buffer, by means of the turn-on transient generation of green fluorescence, with high quantum yields and low detection limits, thus making the system suitable for the detection of abuse drugs, such as MDMA, from ecstasy tablets. PMID- 22314850 TI - The incidence of advanced breast cancer in the West Midlands, United Kingdom. AB - Breast screening of the West Midlands women of 50-64 years started in 1988. Reductions in breast cancer deaths induced by mammography screening should be preceded by reductions in the incidence of advanced breast cancer. We estimated incidence trends in advanced breast cancer from 1989 to 2004. We extracted numbers of cases of breast cancer found in the West Midlands women aged 50-64 years from the Cancer Incidence in Five Continent database. We used published data for estimating the incidence of advanced breast cancer. Then, annual percent changes in incidence rates were computed using join point regression. The incidence rates of lymph node-positive breast cancer increased from 1989 to 1992. In 1993-1995, they decreased below the prescreening level, but from 1996 to 2000, they returned to prescreening levels and then stabilized. From 1989 to 2004, annual percent changes (95% confidence interval) were 2.2% (1.1-3.2%) for node negative cancers and -0.7% (-1.9 to 0.4%) for lymph node-positive cancers. The incidence of cancer greater than 50 mm remained stable from 1989 to 2004 [annual percent change: 0.2% (-2.2 to 2.7%)]. Results from the West Midlands suggest that the breast screening program did not play a significant role in reductions in mortality caused by breast cancer. PMID- 22314851 TI - Role of stopping exposure and recent exposure to asbestos in the risk of mesothelioma. AB - The model of asbestos-related mesothelioma implies that the time since first exposure (latency) is the key determinant of subsequent risk. The role of recent exposure or stopping asbestos exposure, if any, is, however, open to discussion. A literature review was conducted to the end of 2010. In a cohort of 1966 Italian textile workers, the standardized mortality ratio, on the basis of 68 deaths from mesothelioma, was 6627 for workers employed only under the age of 30 years, 8019 for those employed both under the age of 30 years and at the age of 30-39 years, and 5891 for those employed both under the age of 30 years and at the age of 40 years or more. In a cohort of Italian asbestos cement workers, including 135 deaths from pleural cancer, compared with workers who had stopped exposure for 3 15 years, the relative risk (RR) was similar for those still employed (RR=0.67) and for those who had stopped for 30 years or more (RR=0.65). In a British case control study, including 622 cases of mesothelioma and 1420 population controls, the RR substantially increased with increasing duration of exposure under the age of 30 years, but not with exposure at the age of more than 30 years. In the Great Britain Asbestos Workers Survey, including 649 deaths from mesothelioma compared with workers who were still employed and or had stopped for less than 10 years, the multivariate RRs were 0.90 10-20 years after stopping exposure and 0.99 both 20-30 and more than 30 years after stopping. There is consistent evidence showing that, for workers exposed in the distant past, the risk of mesothelioma is not appreciably modified by subsequent exposures, and that stopping exposure does not materially modify the subsequent risk of mesothelioma. PMID- 22314852 TI - Metabolic pathway confirmation and discovery through (13)C-labeling of proteinogenic amino acids. AB - Microbes have complex metabolic pathways that can be investigated using biochemistry and functional genomics methods. One important technique to examine cell central metabolism and discover new enzymes is (13)C-assisted metabolism analysis 1. This technique is based on isotopic labeling, whereby microbes are fed with a (13)C labeled substrates. By tracing the atom transition paths between metabolites in the biochemical network, we can determine functional pathways and discover new enzymes. As a complementary method to transcriptomics and proteomics, approaches for isotopomer-assisted analysis of metabolic pathways contain three major steps (2). First, we grow cells with (13)C labeled substrates. In this step, the composition of the medium and the selection of labeled substrates are two key factors. To avoid measurement noises from non labeled carbon in nutrient supplements, a minimal medium with a sole carbon source is required. Further, the choice of a labeled substrate is based on how effectively it will elucidate the pathway being analyzed. Because novel enzymes often involve different reaction stereochemistry or intermediate products, in general, singly labeled carbon substrates are more informative for detection of novel pathways than uniformly labeled ones for detection of novel pathways(3, 4). Second, we analyze amino acid labeling patterns using GC-MS. Amino acids are abundant in protein and thus can be obtained from biomass hydrolysis. Amino acids can be derivatized by N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide (TBDMS) before GC separation. TBDMS derivatized amino acids can be fragmented by MS and result in different arrays of fragments. Based on the mass to charge (m/z) ratio of fragmented and unfragmented amino acids, we can deduce the possible labeled patterns of the central metabolites that are precursors of the amino acids. Third, we trace 13C carbon transitions in the proposed pathways and, based on the isotopomer data, confirm whether these pathways are active (2). Measurement of amino acids provides isotopic labeling information about eight crucial precursor metabolites in the central metabolism. These metabolic key nodes can reflect the functions of associated central pathways. (13)C-assisted metabolism analysis via proteinogenic amino acids can be widely used for functional characterization of poorly-characterized microbial metabolism(1). In this protocol, we will use Cyanothece 51142 as the model strain to demonstrate the use of labeled carbon substrates for discovering new enzymatic functions. PMID- 22314853 TI - Socio-economic research in support of climate policy development: Mistra's Research Program Clipore. AB - Mistra's Climate Policy Research Program, Clipore, is one of the largest research programs directed to support international climate policy development, involving research groups in Sweden, Norway, United States and India. It has been running from 2004 to 2011 with a budget of more than 100 MSEK (15 M USD). The paper briefly describes the program and its outcomes in relation to climate policy development. Discussion focuses on how the program has been able to be in the front of and include the development of emissions trading systems in Europe and the United States and how the program has been able to follow and produce inputs to the agenda of the United Nations Framework Convention on Climate Change (UNFCCC). The paper also discusses how the program has managed to present its outcomes and maintain an active dialogue with the various stakeholders. The paper emphasises options and obstacles in the communication between science and policy. PMID- 22314854 TI - Short-run allocation of emissions allowances and long-term goals for climate policy. AB - We use economic analysis to evaluate grandfathering, auctioning, and benchmarking approaches for allocation of emissions allowances and then discuss practical experience from European and American schemes. In principle, auctions are superior from the viewpoints of efficiency, fairness, transparency, and simplicity. In practice, auctions have been opposed by important sectors of industry, which argue that carbon pricing without compensation would harm international competitiveness. In the European Union's Emissions Trading System, this concern led to grandfathering that is updated at various intervals. Unfortunately, updating gives industry an incentive to change behavior to influence future allocation. Furthermore, the wealth transferred to incumbent firms can be significantly larger than the extra costs incurred, leading to windfall profits. Meanwhile, potential auction revenues are not available to reduce other taxes. By circumscribing free allocation, benchmarking can target competitiveness concerns, incur less wealth transfer, and provide a strategy consistent with transitioning to auctions in the long run. PMID- 22314855 TI - How should support for climate-friendly technologies be designed? AB - Stabilizing global greenhouse gas concentrations at levels to avoid significant climate risks will require massive "decarbonization" of all the major economies over the next few decades, in addition to the reduced emissions from other GHGs and carbon sequestration. Achieving the necessary scale of emissions reductions will require a multifaceted policy effort to support a broad array of technological and behavioral changes. Change on this scale will require sound, well-thought-out strategies. In this article, we outline some core principles, drawn from recent social science research, for guiding the design of clean technology policies, with a focus on energy. The market should be encouraged to make good choices: pricing carbon emissions and other environmental damage, removing distorting subsidies and barriers to competition, and supporting RD&D broadly. More specific policies are required to address particular market failures and barriers. For those technologies identified as being particularly desirable, some narrower RD&D policies are available. PMID- 22314856 TI - A registry of nationally appropriate mitigation actions: goals, outcomes, and institutional requisites. AB - This article examines key issues in operationalizing a registry of nationally appropriate mitigation actions (NAMAs) undertaken by developing countries party to the United Nations framework convention on climate change. It analyzes goals, outcomes, and institutional prerequisites underlying various proposals to determine how a NAMA mechanism could work in international climate cooperation. The different proposals for how NAMA shall be designed relate to three basic effort-sharing arrangements in a future climate regime: binding commitments for all Parties, purely voluntary commitments for all, and legally binding commitments for Annex I countries but voluntary ones for others. We conclude that a NAMA registry could be designed so as initially to suit all three types of effort-sharing regimes. The article identifies three areas of potential common ground in a registry irrespective of effort-sharing type: the principle of common but differentiated responsibilities, the sustainable development objectives of the Convention, and the need for a systemic transition toward low-carbon energy technologies. PMID- 22314857 TI - Climate policy in India: what shapes international, national and state policy? AB - At the international level, India is emerging as a key actor in climate negotiations, while at the national and sub-national levels, the climate policy landscape is becoming more active and more ambitious. It is essential to unravel this complex landscape if we are to understand why policy looks the way it does, and the extent to which India might contribute to a future international framework for tackling climate change as well as how international parties might cooperate with and support India's domestic efforts. Drawing on both primary and secondary data, this paper analyzes the material and ideational drivers that are most strongly influencing policy choices at different levels, from international negotiations down to individual states. We argue that at each level of decision making in India, climate policy is embedded in wider policy concerns. In the international realm, it is being woven into broader foreign policy strategy, while domestically, it is being shaped to serve national and sub-national development interests. While our analysis highlights some common drivers at all levels, it also finds that their influences over policy are not uniform across the different arenas, and in some cases, they work in different ways at different levels of policy. We also indicate what this may mean for the likely acceptability within India of various climate policies being pushed at the international level. PMID- 22314858 TI - Mapping adaptation opportunities and activities in an interactive atlas. AB - The need for transparency is taking more prominence in international climate negotiations as developed countries pledge large sums of money to foster adaptation efforts in developing countries. Tools that provide accurate and up-to date spatial information that can be easily used and vetted by local practitioners may provide effective and affordable ways to improve transparency. The Global Adaptation Atlas is such a tool, combining vetted, publicly available climate impact data with timely maps of on the ground adaptation projects to highlight confluences of effects of climate change with actions taken to address those effects. Here, we describe the structure and general functions of the Global Adaptation Atlas and explain how it may be utilized to track short-term investments in adaptation. Over longer time scales, it may also help gauge the effectiveness of specific adaptation investments as well as reveal how different climate impacts affect long-term investment in differing regions. PMID- 22314859 TI - How valid are claims for synergy in published clinical studies? AB - BACKGROUND: Clinical trials evaluating drug combinations are often stimulated by claims of synergistic interactions in preclinical models. Overuse or misuse of the term synergy could lead to poorly designed clinical studies. METHODS: We searched PubMed using the terms 'synergy' or 'synergistic' and 'cancer' to select articles published between 2006 and 2010. Eligible studies were those that referred to synergy in preclinical studies to justify a drug combination evaluated in a clinical trial. RESULTS: Eighty-six clinical articles met eligibility criteria and 132 preclinical articles were cited in them. Most of the clinical studies were phase I (43%) or phase II trials (56%). Appropriate methods to evaluate synergy in preclinical studies included isobologram analysis in 18 studies (13.6%) and median effect in 10 studies (7.6%). Only 26 studies using animal models (39%) attempted to evaluate therapeutic index. There was no association between the result of the clinical trial and the use of an appropriate method to evaluate synergy (P=0.25, chi-squared test). CONCLUSIONS: Synergy is cited frequently in phase I and phase II studies to justify the evaluation of a specific drug combination. Inappropriate methods for evaluation of synergy and poor assessment of therapeutic index have been used in most preclinical articles. PMID- 22314860 TI - The management of sleep and circadian disturbance in patients with dementia. AB - Sleep and circadian disturbances are common among patients with dementia. Symptomatic manifestations vary according to dementia subtype, with one commonly shared pattern--the irregular sleep-wake rhythm (ISWR), a circadian disorder characterized by an absence of the sleepwake cycle's circadian synchronization. Hypothesized mechanisms of circadian rhythm disturbance include suprachiasmatic nucleus (SCN) circadian pacemaker damage, pineal gland and melatonin secretion alterations, and reduced zeitbeigers and decreased input to the SCN. Management options include prescribed sleep/wake scheduling, light therapy, melatonin, physical and social activity, and mixed modality. The mixed-modality approach is the most effective method in treating ISWR. Pharmacologic interventions are controversial, with no evidence supporting their effectiveness while associated with multiple side effects. They should be used with caution and only be considered as short-term therapy. All treatment strategies should be individualized to achieve the best outcomes. PMID- 22314861 TI - Restoration of the tibial ACL footprint area and geometry using the Modified Insertion Site Table. AB - PURPOSE: This article is based on the concept of complete footprint restoration. It introduces a "Modified Insertion Site Table" for individual size-matched single- (SB) and double-bundle (DB) ACL reconstruction, which gives surgical guidelines for graft diameters and drill angles according to the restored tibial insertion site area and geometry. METHODS: Potential graft diameters and drill angles were matched for all individual tibial insertion site lengths between 8 and 21 mm. A "Modified Insertion Site Table" was calculated to achieve a maximum of area restoration of the tibial ACL footprint for each of these insertion site lengths. The geometry of the restored footprint was considered. RESULTS: A wide ACL footprint up to a 16-mm-long insertion site might be best restored with a SB , a narrow one with a DB-ACL reconstruction. In a 17-mm-long insertion site, SB- and DB-ACL reconstructions restore a similar amount of footprint area, so geometry considerations of the footprint may decide which surgical technique may be favourized. SB can restore a maximum length of 13.1 mm and DB up to 21 mm. The width of the restored area depends on the drill bit diameter(s) and is larger for SB in most cases. In larger footprints, DB can replicate up to 63% more area and 37% more length than SB-ACL reconstruction. CONCLUSIONS: Anatomical footprint restoration requires assessment of the length, width, and the orientation of the tibial ACL insertion site. Both SB- and DB-ACL reconstruction may achieve a wide range of area and geometric restoration of the individual ACL footprint. While SB ACL reconstruction may be best used for wide insertion sites with up to 16 mm in length, DB-ACL reconstruction has the potential to restore narrow and larger footprints up to 21 mm in length. The "Modified Insertion Site Table" resumes the concept for orientation during surgery PMID- 22314863 TI - Foreword: stem cell applications and tissue engineering approaches in sports medicine- from bench to bedside. AB - Musculoskeletal tissue is frequently damaged or lost in sports injuries. Although surgery has been successful in repairing, realigning and replacing damaged musculoskeletal structures, the challenge of the coming years is to establish whether a paradigm shift from fixation towards regeneration of tissue is possible, clinically feasible and financially viable. There has been an increasing interest in stem cell applications and tissue engineering approaches in surgical practice to deal with damaged or lost tissue caused by sports injuries [1-3]. Tissue engineering is the science of generating tissue using molecular and cellular techniques, combined with material engineering principles, to replace tissue. Although there have been developments in almost all surgical disciplines [1], the greatest advances are being made in orthopaedics, especially in sports medicine [3]. This is due to many factors including the familiarity with bone marrow derived mesenchymal stem cells. PMID- 22314862 TI - Variability in leg muscle power and hop performance after anterior cruciate ligament reconstruction. AB - PURPOSE: The purpose of this prospective study was to describe the variability in leg muscle power and hop performance up to 2 years among patients following ACL reconstruction and specifically to illustrate the effects of various criteria for an acceptable level of muscle function. METHODS: Eighty-two patients (56 men and 26 women)with a mean age of 28 years, who underwent ACL reconstruction using either hamstring tendons (n = 46) or a patellar tendon (n = 36), were assessed pre-operatively and 3, 6, 12 and 24 months post-surgery with a battery of three lower extremity muscle power tests and a battery of three hop tests. RESULTS: Leg symmetry index (LSI) values at group level ranged between 73 and 100% at all follow-ups. When the tests were evaluated individually, patients reached an average LSI of >= 90% at 24 months. The success rate at 24 months for the muscle power test battery, that is,patients with an LSI of >= 90% in all three tests, was 48 and 44% for the hop test battery. The success rate at 24 months for both test batteries on all six muscle function tests was 22%. The criterion of an LSI of >= 80% resulted in 53% of the patients having an acceptable level on all six tests,while with a criterion of an LSI of >= 100%, none of the patients reached an acceptable level. CONCLUSION: At group level and in single muscle function tests, the muscle function outcome 1 and 2 years after ACL reconstruction is satisfactory in the present study and on a par with the results presented in the literature. However,when using more demanding criteria for a successful muscle function outcome, using batteries of tests or increasing the acceptable LSI level from >= 90% to >= 95%or >= 100%, the results are considered to be poor. It is suggested that this should be taken into consideration when presenting results after ACL rehabilitation, deciding on the criteria for a safe return to sports, or designing rehabilitation programmes after ACL reconstruction. LEVEL OF EVIDENCE: Prognostic prospective cohort study, Level I. PMID- 22314864 TI - The role of bone marrow derived mesenchymal stem cells in sports injuries. AB - The therapeutic use of bone marrow-derived mesenchymal stem cells (BM-MSCs) has been applied to many different tissue types that are vulnerable to sports injuries. Avenues of treatment include direct injection of BM-MSCs into the defect, however although minimally invasive, research has highlighted flaws which have been improved upon with the use of scaffolds. BM-MSCs have been applied via many different scaffold types, for example PLGA, collagen gel and coral each with advantages and disadvantages of which can be improved through further research. As a cell source for tissue engineering, BM-MSCs are ideal due to the minimal invasion of aspiration, high in vitro proliferation rate and the ability to maintain their differentiating capacity. The vast majority of these studies are at the small animal stage and therefore further work using larger animal models, and ideally humans is required. PMID- 22314865 TI - The challenges of cartilage repair and the potential of stem cell applications. AB - Articular cartilage injuries pose a treatment challenge. These injuries are a direct cause of pain and loss of function and may precipitate osteoarthritis in the affected joint. Typically affecting a younger, more active population whose expectations of treatment and need for long term joint preservation are high. Articular cartilage poses a treatment challenge in that its capacity for satisfactory healing is limited. The common endpoint of conservative management and traditional surgical interventions is the generation of biomechanically inferior fibrocartilage. Regenerative techniques using human stem cells would appear to represent an exciting modality for the production of true hyaline cartilage with material and biological properties suited for lasting function. This review article summarises the current research regarding the use of human stem cells in the treatment of such injuries. PMID- 22314866 TI - Current cell-based strategies for knee cartilage injuries. AB - Cartilage is frequently damaged and shows little or no capacity for repair. Injuries that extend to the subchondral level show some capacity for repair due to the release of bone marrow derived mesenchymal stem cells. This technique is employed in techniques like the microfracture but they are only appropriate for smaller cartilage defects. Autologous Chondrocyte Implantation (ACI) and Matrix carried Autologous Chondrocyte Implantation (MACI) are currently used in clinical practice to treat larger full thickness chondral defects in the knee with similar results. MACI does however have a number of advantages including its amenability to be performed arthroscopically or through a more limited approach without requiring arthrotomy. More definitive studies showing the long-term effects of the two cell-based treatments and comparing them are however awaited. There are a small number of studies using mesenchymal stem cells and further in vitro and in vivo studies are needed before this treatment is optimised. This review discussed these treatment options and provides an evidence-based approach to current clinical treatments. PMID- 22314867 TI - Stem cells for tendon and ligament tissue engineering and regeneration. AB - Tendons and ligaments are frequently injured. Due to their relatively avascular nature, repair is slow and often incomplete. Stem cells offer a new approach to augment healing of native tissues, as well as providing materials to surgically replace injured structures that are beyond repair. Here we discuss the various roles of stem cells in natural repair processes compared to engineered tissues to assist healing or replace tissues. PMID- 22314868 TI - Functional tissue engineering for rotator cuff tendons. AB - Rotator cuff disease is becoming more prevalent and is a significant source of pain and disability. Current methods of treating rotator cuff dysfunction have inconsistent results and there is a high rate of recurrent tear and failure. This has prompted the search for novel solutions and the use of tissue engineered strategies and approaches. This article looks at the current state of tissue engineering methods for rotator cuff regeneration. PMID- 22314869 TI - Single molecule fluorescence correlation spectroscopy of single apoptotic cells using a red-fluorescent caspase probe. AB - The detection of single molecules in single cells has enabled biochemical analyses to be conducted with high sensitivity and high temporal resolution. In this work, detection of apoptosis was studied by single molecule fluorescence correlation spectroscopy (FCS) in single living cells. Caspase activity was assayed using a new red fluorogenic probe that avoids the spectral overlap of green fluorescent probes and cell autofluorescence. This new probe, 2SBPO-Casp, was synthesized by coupling a water-soluble Nile Blue derivative (2SBPO) to an aspartic acid residue. Upon apoptosis induction and caspase activation, free 2SBPO dye is shown to accumulate inside the cell after probe cleavage. In previous work in our lab, single molecule fluorescence in single apoptotic cells was detected 45 min after induction using a rhodamine 110-based probe. However, significant statistical analysis was needed to exclude false positives. The use of 2SBPO-Casp overcomes the autofluorescence problem and offers a steady fluorescence signal. In our single molecule FCS measurements, Ramos cells were determined apoptotic on the basis of their correlation coefficient value (R(2)). Cells that contain an R(2) >= 0.65 were identified as highly correlated and therefore determined to be apoptotic. Single apoptotic cells identified in this manner were found as early as 30 min after induction and the number of apoptotic cells reached a peak value at the 3rd hour, which is consistent with other techniques. Using single molecule techniques and a new apoptosis probe, the temporal dynamics were elucidated with better sensitivity and resolution than in previous studies. PMID- 22314870 TI - Light-mediated heterogeneous cross dehydrogenative coupling reactions: metal oxides as efficient, recyclable, photoredox catalysts in C-C bond-forming reactions. AB - Let there be light: A heterogeneous photocatalytic system based on easily recyclable TiO(2) or ZnO allows cross dehydrogenative coupling reactions of tertiary amines. The newly developed protocols have successfully been applied to various C-C and C-P bond-forming reactions to provide nitro amines as well as amino ketones, nitriles and phosphonates. PMID- 22314871 TI - Brain metabolism and spatial memory are affected by portal hypertension. AB - Portal hypertension is a major complication of cirrhosis that frequently leads to a neuropsychiatric disorder that affects cognition. The present study was undertaken in order to compare the performance of sham-operated rats (SHAM) and portal hypertension rats (PH) in reference memory tasks in the Morris water maze (MWM). Two groups of animals were used: SHAM group (n=12) was used as a control group and PH group (n=12) by the triple portal vein ligation method was used as an animal model of early evolutive phase of PH. The portal pressure was measured in the splenic parenchyma. Our work shows that spatial learning in the MWM is not impaired in PH group although this group showed a one-day delay in the task acquisition compared to the SHAM group. We assessed the brain metabolic activity of the animals by means of cytochrome c-oxidase (COx) histochemistry. Significant changes were found in the CA3, dentate gyrus, basolateral, medial, lateral and central amygdala, showing lower COx activity in the PH group as compared to the SHAM group in all cases. We found no changes in metabolic activity in prefrontal cortex and CA1 area between groups. In fact, different neural networks were shown according to the execution level of the subjects. The early PH evolution induced changes in brain metabolic activity without biggest alterations in spatial memory. PMID- 22314872 TI - Exercise during pregnancy: fetal responses to current public health guidelines. AB - OBJECTIVE: To evaluate acute fetal responses to individually prescribed exercise according to existing guidelines (U.S. Department of Health and Human Services) in active and inactive pregnant women. METHODS: Forty-five healthy pregnant women (15 nonexercisers, 15 regularly active, 15 highly active) were tested between 28 0/7 and 32 6/7 weeks of gestation. After a treadmill test to volitional fatigue, target heart rates were calculated for two subsequent 30-minute treadmill sessions: 1) moderate intensity (40-59% heart rate reserve); and 2) vigorous intensity (60-84%). All women performed the moderate test; only active women performed the vigorous test. Fetal well-being measures included umbilical artery Dopplers, fetal heart tracing and rate, and biophysical profile. Measures were obtained at rest and immediately postexercise. RESULTS: Groups were similar in age, body mass index, and gestational age. Maternal resting heart rate in the highly active group (61.6 +/- 7.2 beats per minute [bpm]) was significantly lower than the nonexercise (79.0 +/- 11.6 bpm) and regularly active (71.9 +/- 7.4 bpm) groups (P<.001). Treadmill time was longer in highly active (22.3 +/- 2.9 minutes) than regularly active (16.6 +/- 3.4) and nonexercise (12.1 +/- 3.6) groups (P<.001), reflecting higher fitness. With moderate exercise, all umbilical artery Doppler indices were similar pre-exercise and postexercise among groups. With vigorous exercise, Dopplers were similar in regularly and highly active women with statistically significant decreases postexercise (P<.05). The group * time interaction was not significant. Postexercise fetal heart tracings met criteria for reactivity within 20 minutes after all tests. Biophysical profile scores were reassuring. CONCLUSION: This study supports existing guidelines indicating pregnant women may begin or maintain an exercise program at moderate (inactive) or vigorous (active) intensities. PMID- 22314873 TI - Postoperative levonorgestrel-releasing intrauterine system for pelvic endometriosis-related pain: a randomized controlled trial. AB - OBJECTIVES: To estimate the effectiveness of a postoperative levonorgestrel releasing intrauterine system for relieving pelvic pain in patients with endometriosis. METHODS: A double-blind randomized controlled trial was conducted in 55 patients with endometriosis and moderate-to-severe dysmenorrhea (visual analog scale, greater than 50 mm) undergoing laparoscopic conservative surgery. After surgery, patients were randomized to a levonorgestrel-releasing intrauterine system (n=28) or expectant management (n=27) group. Primary outcome was the change of dysmenorrhea visual analog scale. Secondary outcomes included changes of pelvic pain and dyspareunia visual analog scale, Short Form-36 score, and adverse effects. RESULTS: The two groups were comparable in age, body mass index, parity, and baseline pain scores. At 12 months, the levonorgestrel releasing intrauterine system group had a significantly lower median value of dysmenorrhea and noncyclic pelvic pain score. Compared with the control group, the levonorgestrel-releasing intrauterine system group had greater reduction in dysmenorrhea visual analog scale (-81.0 compared with -50.0 mm, P=.006) and pelvic pain visual analog scale (-48.5 compared with -22.0 mm, P=.038) but a comparable reduction in dyspareunia visual analog scale (-15.0 compared with 19.0 mm, P=.831). Two patients in levonorgestrel-releasing intrauterine system group (7.4%) and nine in the expectant management group (39.1%) had recurrent dysmenorrhea within 1 year postoperatively (P=.014). Number-needed-to-treat to prevent one case with recurrent dysmenorrhea within the first year was three cases. The Short Form-36 scores improved in the levonorgestrel-releasing intrauterine system group but did not change in the expectant management group. There was no serious adverse event during the study period. CONCLUSION: The levonorgestrel-releasing intrauterine system is effective and well accepted for long-term therapy after conservative surgery for patients with moderate to severe pain related to endometriosis. It can improve the patient's quality of life, including physical and mental health. PMID- 22314874 TI - Chemistry in solution: recent techniques and applications using soft X-ray spectroscopy. AB - The aim of a more precise knowledge about molecular structures and the nature of chemical bonds is the driving force behind the development of numerous experimental methods and theories. Recent soft X-ray based techniques provide novel opportunities for tackling the structure and the dynamics of chemical and biochemical systems in solution. In our research group we are developing experimental methods for mapping the electronic structure and dynamics of molecular systems in solution during bond-building and breaking using soft X-ray absorption and emission spectroscopy. The combination of such recent developments with conventional spectroscopy as well as theoretical modeling allows us to address open questions about hydrogen bonds, thermodynamics and active centers of biological systems. Based on the core-hole clock and pump-probe spectroscopy dynamics on the time scale from sub-femtoseconds up to picoseconds can be revealed. PMID- 22314875 TI - Familial renal glucosuria: a clinicogenetic study of 23 additional cases. AB - BACKGROUND: Familial renal glucosuria (FRG) is an inherited renal tubular disorder characterized by persistent isolated glucosuria in the absence of hyperglycemia that is caused by mutations in the sodium-glucose cotransporter SGLT2 coding gene, SLC5A2. OBJECTIVE: We conducted molecular and phenotype analyses of a cohort of 23 unrelated Korean children with FRG. METHODS: Mutational analysis of the SLC5A2 gene was conducted in this multicenter study organized by the Korean Society of Pediatric Nephrology. RESULTS: A total of 21 different SLC5A2 mutations were detected, including 19 novel mutations. All patients had at least one mutated allele; ten patients had homozygous or compound heterozygous mutations and 13 patients had a single heterozygous mutation. Most mutations were private. Patients with two mutations were diagnosed earlier with larger amounts of urinary glucose excretion than patients with single mutations. Pedigree analysis data were consistent with the inheritance of a codominant trait with incomplete penetrance. CONCLUSIONS: These findings extend the allelic heterogeneity in FRG and confirm previous observations of inheritance and genotype-phenotype correlation in patients with this disease. PMID- 22314876 TI - Venous malformations of the temporal bone are a common feature in CHARGE syndrome. AB - OBJECTIVES/HYPOTHESIS: CHARGE (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital and/or urinary abnormalities, and Ear abnormalities and/or deafness) syndrome is a genetic disorder with prominent otolaryngologic features including choanal atresia and inner ear malformations. Recent experience with venous malformations during cochlear implant surgery prompted this study to define the spectrum of venous abnormalities in CHARGE and their surgical implications in otology. STUDY DESIGN: Retrospective review of medical and radiologic records from databases of patients with CHARGE syndrome from three tertiary care academic medical centers. METHODS: Eighteen patients with CHARGE for whom temporal bone CT scans were available were included in the review. RESULTS: Venous anomalies of the temporal bone were present in 10 of 18 (56%) patients. The most common were large emissary veins (n = 5). In two of these cases, these veins were associated with an ipsilateral a hypoplastic sigmoid sinus or jugular foramen. Other abnormalities included an aberrant petrosal sinus, venous lakes in proximity to the lateral venous sinus, condylar canal veins, and jugular bulb abnormalities, including a high riding bulb obscuring the round window niche and a dehiscent jugular bulb. In four of six patients undergoing cochlear implantation, the course of the aberrant vessel necessitated a change in the surgical approach, either during mastoidectomy or placement of the cochleostomy. CONCLUSIONS: Temporal bone venous abnormalities are a common feature in CHARGE syndrome. The pattern of venous abnormality suggests that there is a failure of the sigmoid sinus/jugular bulb to fully develop, resulting in persistence of emissary veins. Recognition of these abnormal venous structures during otologic surgery is critical to avoiding potentially catastrophic bleeding. PMID- 22314877 TI - A 3D system for culturing human articular chondrocytes in synovial fluid. AB - Cartilage destruction is a central pathological feature of osteoarthritis, a leading cause of disability in the US. Cartilage in the adult does not regenerate very efficiently in vivo; and as a result, osteoarthritis leads to irreversible cartilage loss and is accompanied by chronic pain and immobility (1,2). Cartilage tissue engineering offers promising potential to regenerate and restore tissue function. This technology typically involves seeding chondrocytes into natural or synthetic scaffolds and culturing the resulting 3D construct in a balanced medium over a period of time with a goal of engineering a biochemically and biomechanically mature tissue that can be transplanted into a defect site in vivo (3-6). Achieving an optimal condition for chondrocyte growth and matrix deposition is essential for the success of cartilage tissue engineering. In the native joint cavity, cartilage at the articular surface of the bone is bathed in synovial fluid. This clear and viscous fluid provides nutrients to the avascular articular cartilage and contains growth factors, cytokines and enzymes that are important for chondrocyte metabolism (7,8). Furthermore, synovial fluid facilitates low-friction movement between cartilaginous surfaces mainly through secreting two key components, hyaluronan and lubricin (9 10). In contrast, tissue engineered cartilage is most often cultured in artificial media. While these media are likely able to provide more defined conditions for studying chondrocyte metabolism, synovial fluid most accurately reflects the natural environment of which articular chondrocytes reside in. Indeed, synovial fluid has the advantage of being easy to obtain and store, and can often be regularly replenished by the body. Several groups have supplemented the culture medium with synovial fluid in growing human, bovine, rabbit and dog chondrocytes, but mostly used only low levels of synovial fluid (below 20%) (11-25). While chicken, horse and human chondrocytes have been cultured in the medium with higher percentage of synovial fluid, these culture systems were two-dimensional (26-28). Here we present our method of culturing human articular chondrocytes in a 3D system with a high percentage of synovial fluid (up to 100%) over a period of 21 days. In doing so, we overcame a major hurdle presented by the high viscosity of the synovial fluid. This system provides the possibility of studying human chondrocytes in synovial fluid in a 3D setting, which can be further combined with two other important factors (oxygen tension and mechanical loading) (29,30) that constitute the natural environment for cartilage to mimic the natural milieu for cartilage growth. Furthermore, This system may also be used for assaying synovial fluid activity on chondrocytes and provide a platform for developing cartilage regeneration technologies and therapeutic options for arthritis. PMID- 22314878 TI - Deficit of interleukin-7 in serum of patients with Crohn's disease. PMID- 22314879 TI - Function biomedical informatics research network recommendations for prospective multicenter functional MRI studies. AB - This report provides practical recommendations for the design and execution of multicenter functional MRI (MC-fMRI) studies based on the collective experience of the Function Biomedical Informatics Research Network (FBIRN). The study was inspired by many requests from the fMRI community to FBIRN group members for advice on how to conduct MC-fMRI studies. The introduction briefly discusses the advantages and complexities of MC-fMRI studies. Prerequisites for MC-fMRI studies are addressed before delving into the practical aspects of carefully and efficiently setting up a MC-fMRI study. Practical multisite aspects include: (i) establishing and verifying scan parameters including scanner types and magnetic fields, (ii) establishing and monitoring of a scanner quality program, (iii) developing task paradigms and scan session documentation, (iv) establishing clinical and scanner training to ensure consistency over time, (v) developing means for uploading, storing, and monitoring of imaging and other data, (vi) the use of a traveling fMRI expert, and (vii) collectively analyzing imaging data and disseminating results. We conclude that when MC-fMRI studies are organized well with careful attention to unification of hardware, software and procedural aspects, the process can be a highly effective means for accessing a desired participant demographics while accelerating scientific discovery. PMID- 22314880 TI - Neoadjuvant chemotherapy for invasive bladder cancer. AB - Neoadjuvant cisplatin-based combination chemotherapy is an established standard for resectable muscle-invasive bladder cancer, a disease with a pattern of predominantly distant and early recurrences. Pathologic complete remission appears to be an intermediate surrogate for survival when employing combination chemotherapy. Moreover, baseline host and tumor tissue studies may enable the discovery of biomarkers predictive of activity. The neoadjuvant setting also provides a window of opportunity to evaluate novel biologic agents or rational combinations of biologic agents to obtain a signal of biologic activity. The residual tumor after neoadjuvant therapy may be exploited to study the mechanism of action and resistance. Cisplatin-ineligible patients warrant the evaluation of tolerable neoadjuvant regimens. Given that bladder cancer is characterized by initial localized presentation in the vast majority of cases, the paradigm of neoadjuvant therapy may expedite the development of novel systemic agents. PMID- 22314881 TI - Radical prostatectomy as primary treatment of high-risk prostate cancer. AB - High-risk prostate cancer (PCa), established according to the d'Amico criteria or other prognostic tools, remains very heterogeneous, including a third of patients with excellent prognosis in whom surgical treatment can result in long-term progression-free survival. In contrast, a substantial proportion of high risk will not be cured by local treatment alone and might benefit from a more aggressive multimodal adjuvant treatment strategy. However, to date, except in one adjuvant radiotherapy series, no neoadjuvant or adjuvant therapy has shown a survival improvement after radical prostatectomy for high-risk PCa. Recent observational studies tend to prove that radical prostatectomy may offer benefits over radiotherapy in disease-free and overall survival. However, good Level 1 evidence is lacking and further prospective studies are warranted to directly compare the outcomes of radical prostatectomy to combined radiation and hormonal therapy in high-risk patients. PMID- 22314882 TI - Patients' pathway to emergency care: is the emergency department their first choice of care? AB - OBJECTIVES: To investigate whether patients came directly to the emergency department (ED) or whether they had taken any other actions or activities within the healthcare system before attending the ED. An additional aim was to increase our understanding of the potential determinants between patients' ED-seeking behaviour and patient-related data. METHODS: This prospective descriptive study was carried out at the ED at a level one trauma centre at a university hospital in Sweden. During 12 weeks in 2008, a 20-item study-specific questionnaire was distributed by research assistants to patients arriving either by their own means or by ambulance to the ED. In addition, patient-specific data were gathered from the electronic patient records. RESULTS: A total of 2014 patients participated in the study, of whom 1192 (59%) reported to have carried out healthcare-related actions or activities before their visit to the ED. A general practitioner was the most common (29.1%) healthcare provider to have been in contact with. Female patients and patients with a longer duration of symptoms sought other health caregivers before the ED visit to a significantly higher extent (P<0.001, 0.003). Other caregivers' referral rate to the ED was 60.1-87.9%. Accessibility to other caregivers was generally rated as easy. CONCLUSION: A large proportion of ED patients sought previous healthcare before seeking care at the ED. Female patients and patients with longer symptom duration more often sought other caregivers before seeking ED care. PMID- 22314886 TI - Neuroprotective effects of testosterone on motoneuron and muscle morphology following spinal cord injury. AB - Treatment with testosterone is neuroprotective/neurotherapeutic after a variety of motoneuron injuries. Here we assessed whether testosterone might have similar beneficial effects after spinal cord injury (SCI). Young adult female rats received either sham or T9 spinal cord contusion injuries and were implanted with blank or testosterone-filled Silastic capsules. Four weeks later, motoneurons innervating the vastus lateralis muscle of the quadriceps were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. Soma volume, motoneuron number, lesion volume, and tissue sparing were also assessed, as were muscle weight, fiber cross sectional area, and motor endplate size and density. Contusion injury resulted in large lesions, with no significant differences in lesion volume, percent total volume of lesion, or spared white or gray matter between SCI groups. SCI with or without testosterone treatment also had no effect on the number or soma volume of quadriceps motoneurons. However, SCI resulted in a decrease in dendritic length of quadriceps motoneurons in untreated animals, and this decrease was completely prevented by treatment with testosterone. Similarly, the vastus lateralis muscle weights and fiber cross-sectional areas of untreated SCI animals were smaller than those of sham-surgery controls, and these reductions were both prevented by testosterone treatment. No effects on motor endplate area or density were observed across treatment groups. These findings suggest that regressive changes in motoneuron and muscle morphology seen after SCI can be prevented by testosterone treatment, further supporting a role for testosterone as a neurotherapeutic agent in the injured nervous system. PMID- 22314887 TI - A "one-pot" multicomponent approach to polysubstituted 4-aminopyridines. AB - A novel and facile domino reaction has been developed to synthesize a variety of polysubstituted 4-aminopyridines from alpha-azidovinylketones, aldehydes and methylamine derivatives in reasonably good yields under mild conditions. Additionally, a possible mechanism is proposed. PMID- 22314888 TI - We're talking about feedback... aren't we? PMID- 22314890 TI - Liver regeneration after partial hepatectomy: inconsistent results of expression screenings for human, mouse, and rat microRNAs. PMID- 22314891 TI - Randomized trial of a comparison of the efficacy of TVT-O and single-incision tape TVT SECUR systems in the treatment of stress urinary incontinent women--2 year follow-up. AB - INTRODUCTION AND HYPOTHESIS: The aim of this study was to compare the efficacy of the use of tension-free vaginal tape obturator (TVT-O) and single-incision TVT SECUR, hammock and U approach (TVT-S, H and U), in the treatment of urodynamic stress urinary incontinence (SUI). METHODS: This single-center randomized three arm trial compared the objective and subjective efficacy and early failure rate of the TVT-O and TVT-S H and U approach by objective criteria (cough test) and subjective criteria using the International Consultation on Incontinence Questionnaire--Short Form (ICIQ-UI SF). The objective efficacy rate was defined as the number of patients with a negative cough stress test. Subjective cure was defined by no stress leakage of urine after surgery based on the evaluation of ICIQ-UI SH (when patients ticked "Never"/"Urine does not leak" in answer to question 6: When does urine leak?). Objective and subjective efficacy were evaluated using Last Failure Carried Forward analysis, i.e., final analysis also included patients with early failure. To describe outcome at different time points, the Last Observation Carried Forward method was also implemented. RESULTS: One hundred ninety-seven women with proven SUI were randomized into three groups--TVT-O (n = 68), TVT-S H (n = 64), and TVT-S U (n = 65). Each patient allocated to a treatment group received the planned surgery. There were no differences in each group in preoperative characteristics. Median follow-up after surgery was 2 years (SD, 0.8; range, 0.1 to 3.8 years). Of the subjects, 92.6% in the TVT-O group, 68.8% in the TVT-S H group, and 69.2% in the TVT-S U group had negative stress test (p < 0.001). Of the subjects, 85.3 % in the TVT-O group, 68.8% in the TVT-S H group, and 61.5% in the TVT-S U group were subjectively continent (p = 0.02). CONCLUSIONS: Our study demonstrated a significantly lower subjective and objective cure rate in the single-incision TVT group compared to the TVT-O group. PMID- 22314892 TI - Anterior colporrhaphy does not induce bladder outlet obstruction. AB - INTRODUCTION AND HYPOTHESIS: We aimed to evaluate if anterior colporrhaphy causes incomplete voiding due to bladder outlet obstruction. METHODS: Women scheduled for anterior colporrhaphy were asked to undergo multichannel urodynamic investigation before surgery and the first postoperative day. Bladder outlet obstruction was assessed using the Blaivas-Groutz voiding nomogram. Maximum flow rate, detrusor pressure and residual volume were compared between pre- and postoperative measurements and between women with and without an abnormal post void residual volume (PVR; volume exceeding 150 ml). RESULTS: Seventeen women participated. One woman who was unobstructed before surgery was obstructed after surgery. Overall, detrusor pressure and maximum flow rate before and after surgery did not differ. After surgery, six women had an abnormal PVR, one was unable to void, four were mildly obstructed and one moderately obstructed. CONCLUSION: Urodynamic investigation the first day after anterior colporrhaphy did not show that anterior colporrhaphy induces bladder outlet obstruction. The explanation for postoperative urinary retention can therefore also lie in nonanatomical causes such as postoperative pain and psychological factors. PMID- 22314893 TI - Ketotifen is an antimalarial prodrug of norketotifen with blood schizonticidal and liver-stage efficacy. AB - Ketotifen is known to exhibit antimalarial activity in mouse and monkey malaria models. However, the low plasma levels and short half life of the drug do not adequately explain its in vivo efficacy. We synthesized most of the known metabolites of ketotifen and evaluated their antimalarial activity and pharmacokinetics in mice. Norketotifen, the de-methylated metabolite of ketotifen, was a more potent antimalarial in vitro as compared to ketotifen, and exhibited equivalent activity in vivo against asexual blood and developing liver stage parasites. After ketotifen dosing, norketotifen levels were much higher than ketotifen relative to the IC50s of the compounds against Plasmodium falciparum in vitro. The data support the notion that the antimalarial activity of ketotifen in mice is mediated through norketotifen. PMID- 22314894 TI - Pharmacokinetic study of unbound forsythiaside in rat blood and bile by microdialysis coupled with HPLC method. AB - In the present study, an in vivo microdialysis sampling method coupled to HPLC was applied for the determination of unbound forsythiaside in rat blood and bile. Microdialysis probes were inserted into the jugular vein and bile duct of rats, and then blood and bile dialysates were collected at regular time intervals after intravenous administration of forsythiaside (50 mg/kg). Dialysate were directly injected into HPLC system. Forsythiaside was separated on a C18 column eluted with the mobile phase of acetonitrile-water-formic acid (16:84:0.2, v/v/v) at a flow rate of 0.8 mL/min. The wavelength of the ultraviolet detector was set at 332 nm. The lowest limit quantification was 0.2 MUg/mL for forsythiaside. Excellent linearity was found to be over a concentrate range of 0.2-100 MUg/mL. The main pharmacokinetic parameters of unbound forsythiaside in rat blood and bile were obtained, Furthermore, the bile-to-blood distribution ratio (AUC(bile)/AUC(blood)) of forsythiaside was 0.32 +/- 0.06. The results indicated that forsythiaside went through hepatobiliary excretion. PMID- 22314895 TI - NJPS: looking forward. PMID- 22314896 TI - You can get there from here: acetone, anionic ketones and even-carbon fatty acids can provide substrates for gluconeogenesis. AB - Although the literature contains studies published more than 30 years ago showing that acetone is not metabolically inert, it is common to find biochemistry textbooks and current research publications asserting that acetone is a 'dead end' metabolite. In fact, acetone derived from the non-enzymatic breakdown of acetoacetate in ketotic individuals or from the oxidation of ingested isopropanol can be metabolized to D-lactate and pyruvate, and ultimately glucose. This report describes the reactions and pathways that account for the metabolism of acetone in humans. PMID- 22314897 TI - Catecholamines inhibit gastric epithelial [RGM-1] cell proliferation via beta adrenoceptors. AB - Catecholamines have been implicated in the modulation of normal cell growth, exerting inhibitory or excitatory control depending on the cell type. However, there is a dearth of information on the role of adrenergic mediators in gastric cell proliferation. In the present study, the effects of adrenaline (ADR) and noradrenaline (NOR) on mucosal cell growth and the cell cycle were evaluated in vitro using a normal rat gastric mucosal cell line RGM-1. Cell proliferation was assessed using [3H]-thymidine incorporation and cell cycle patterns were determined by DNA labeling with propidium iodide and flow cytometric quantification. The expressions of adrenoceptors in RGM-1 were determined by Western blot. ADR (0.01 - 10uM) and NOR (0.01 - 10uM) inhibited the growth of RGM 1 cells in a concentration-dependent manner. Pre-treatment of cells with ADR and NOR also inhibited the proliferation stimulated by epidermal growth factor (EGF). Neither phentolamine (non-selective alpha-adrenergic blocker), methoxamine (alpha1-selective agonist) nor clonidine (alpha2-selective agonist) significantly affected the inhibition of cell proliferation produced by ADR and NOR. Propranolol (non-selective beta-adrenergic blocker) and butoxamine (selective beta2-adrenergic blocker) significantly (but not totally) reversed the inhibitory action of ADR on cell proliferation. Furthermore, procaterol (selective beta-2 agonist) but not dobutamine (selective beta-1 agonist) had effects similar to those produced by ADR and NOR. Exposure of RGM-1 cells to both ADR and NOR caused significant inhibition of the G1 - S cycle progression as evidenced by the higher percentage of the G0/G1 phase and a decreased S- phase. This effect was blocked by pre-treatment with propranolol but not phentolamine These results indicate that catecholamines inhibit the proliferation of RGM-1 cells probably partly through beta-2 receptors. PMID- 22314898 TI - Effect of melatonin and caffeine interaction on caffeine induced oxidative stress and sleep disorders. AB - Effect of interaction of melatonin and caffeine on caffeine induced oxidative stress and sleep disorders was studied. Fifteen wistar rats were randomly assigned into three study groups. The animals in group 1 (the control) received a placebo of 10.0 ml distilled water via gastric intubation. The hosts in groups 2 and 3 were treated with 100 mg caffeine/ kg, or melatonin/ kg, respectively, in a total volume of 10.0 ml vehicle. The experiment lasted for 30 days. One day after the final exposure, the animals were euthanized by inhalation of overdose of chloroform. Blood was collected by cardiac puncture. Serum was obtained by centrifugation (6000 Xg, 30 mins), and used for serum total protein and serum blood urea nitrogen levels. The brain of each rat was also harvested and processed into whole homogenate, frozen in liquid nitrogen (N2), and maintained at -80oC until used for total brain cholesterol and tryptophan levels. The results showed that interaction of melatonin and caffeine enhanced protein synthesis; stimulated gonadotrophin release, and could be used as oral contraceptive for women, and may be beneficial in the treatment of impotence (androgen depression), leading to improved reproductive and sex life; stimulated tryptophan metabolism, which prevents vitamin B6 deficiency, anemia, negative nitrogen balance, tissue wasting and accumulation of xanthurenic acid, which promotes sleep; and could be beneficial in the treatment of hyper cholesterolemia, thereby preventing coronary heart disease, and post menopausal osteoporosis. PMID- 22314899 TI - Dyselectrolytemia in chronic obstructive pulmonary diseases with acute exacerbation. AB - Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of mortality and morbidity world wide. Due to lack of awareness about the precipitating factors and predictors of prognosis, cases of acute exacerbation of COPD often suffer the fatal outcomes. In our study we assessed the levels of serum sodium and potassium in subjects with acute episodes of COPD and their healthy controls. We found a significantly low level of serum sodium (133+/- 6.86 meq/lit) and potassium (3.39 +/- 0.96 meq/L)) in subjects with acute exacerbation of COPD than their healthy counterparts [sodium-142 +/- 2.28 meq/L and potassium- 4.52 +/- 0.02 meq/L (p <0.05)]. Therefore, our study findings suggest that, serum sodium and potassium levels may get deranged in subjects with acute exacerbations of COPD which should be routinely checked for to avoid fatal outcomes. PMID- 22314900 TI - Aqueous and ethanolic leaf extracts of Ocimum basilicum (sweet basil) protect against sodium arsenite-induced hepatotoxicity in Wistar rats. AB - We evaluated the effects of aqueous and ethanolic leaf extracts of Ocimum basilicum (sweet basil) on sodium arsenite-induced hepatotoxicity in Wistar rats. We observed that treatment of the animals with the extracts before or just after sodium arsenite administration significantly (p < 0.05) reduced mean liver and serum gamma-Glutamyl transferase (gammaGT), and serum alkaline phosphatase (ALP) activities when compared with the group administered the toxin alone. In addition, treatments of the animals with aqueous or ethanolic extract of O. basilicum before the administration of sodium arsenite resulted in the attenuation of the sodium arsenite-induced aspartate and alanine aminotransferase activities: ALT (from 282.6% to 167.7% and 157.8%), AST (from 325.1% to 173.5% and 164.2%) for the group administered sodium arsenite alone, the aqueous extracts plus sodium arsenite, and ethanolic extracts plus sodium arsenite respectively, expressed as percentage of the negative control. These findings support the presence of hepatoprotective activity in the O.basilicum extracts. PMID- 22314901 TI - Anti-histaminic potential of fractions from Hedranthera barteri [(Hook F.) Pichon] root in laboratory rodents. AB - Hedranthera barteri, anti-inflammatory activity, anti-nociceptive activity, anti histaminic activityL. (HB) is used in the treatment of painful conditions and oedema amongst its folkloric use. The hexane and ethyl acetate fractions of the root of H. barteri were investigated for anti-nociceptive and antiinflammatory properties and probable mechanism of action. Hot plate, tail flick, formalin induced oedema and acetic acidinduced writhing tests were employed to investigate the anti-nociceptive activity while the anti-inflammatory activity was investigated using carrageenan-induced paw oedema. Anti-histaminic potential of HB root extracts on the rat peritoneal mast cells (RPMCs) was explored through pectrofluorometric method. The root was screened for its phytochemical components. The HB root contains alkaloids,cardenolides and saponins. HXHBR exhibited higher anti-inflammatory potentials (P <0.001). HXHBR dose-dependently (P <0.01) reduced the histamine release from the rat peritoneal mast cells which is comparable with a standard anti-histaminic drug, ketotifen. These results showed that EAHBR and HXHBR possess anti-nociceptive and anti-inflammatory activities, and suggested its mechanism of action through the inhibition of histamine, an inflammatory mediator, usually released during the early phase of allergic responses and chronic phase of inflammatory pain. Flavonoids, alkaloids and/or saponins present in HB root may be responsible for its anti-nociceptive and anti-inflammatory properties. PMID- 22314902 TI - Attitude of infertile women to child adoption in Nigeria. AB - Infertility has serious consequences especially in Africa where a high premium is place on child bearing. An interviewer-administered questionnaire was administered on 396 consenting women seeking infertility treatment at the gynaecological clinic of the University College Hospital, Ibadan in an attempt to assess the attitude of infertile women in Nigeria to child adoption and its acceptability as a management option for infertility. Most (64%) believed its culturally unacceptable and only 17% will try it as an option. Sustained advocacy, community mobilization and enactment of supportive laws were some of the suggestions made by respondents to improve its uptake. PMID- 22314903 TI - Anaphe venata larva extract-induced purposeless chewing in rats: the role of cholinergic, GABAergic and opioid systems. AB - Seasonal ataxia was reported in humans following the consumption ofAnaphe venata larva as protein supplement in diet and altered motor function in rodents when the extract was administered intraperitoneally. In this study we investigated the effect of the crude aqueous and Phosphate Buffer Saline (PBS) extracts of this larva on altered spontaneous rat behavior in a novel environment particularly chewing behaviour, with a view to determine the mechanism(s) involved in these behavioural alteration. Animals were randomly assigned into four groups (n = 6-12 per group) and graded doses of aqueous and PBS extracts (100-400 mg/kg) were administered dissolved in saline intraperitoneally (i.p.) to each animal in the experimental groups. The control group received an equivalent volume of saline. Behavioral scores were recorded for a period of 30 minutes after the administration of saline or extract. The role of various receptors in the extract induced chewing was evaluated using known receptor agonist/antagonists. Results revealed a significant increase in purposeless chewing (F (7, 95) = 7.85; p <0.05) by the aqueous extract compared to saline control at all dose levels, which was significantly attenuated by scopolamine (3 mg/kg, i.p) and thiamine (1 mg/kg, i.p) respectively (p <0.05); while flumazenil (2 mg/kg, i.p) and naloxone (2.5 mg/kg, i.p) did not alter the induced purposeless chewing behaviour. Also, administration of PBS induced a significant (F (7, 95) = 6.11; p <0.05) increase in chewing behaviour but only at 400 mg/kg dose level which was attenuated by scopolamine (3 mg/kg, i.p); while flumazenil (2 mg/kg, i.p), naloxone (2.5 mg/kg, i.p), and thiamine (1 mg/kg, i.p) potentiated purposeless chewing behaviour respectively. It may therefore be concluded from this study that Anaphe extract induced purposeless chewing behaviour in rat is mediated via the activation of cholinergic neurotransmission which is modulated by GABAergic and opioid receptor systems. PMID- 22314904 TI - Effect of intragastric administration of crude aqueous leaf extract of Anacardium occidentale on gastric acid secretion in rats. AB - The effect of an aqueous leaf extract ofAnacardium occidentale on gastric acid secretion was tested in rats. Twenty (20) Wistar albino rats were used for the gastric acid assay experiment. The rats were divided into 2 groups of 10 each. Gastric acid output was determined by continuous perfusion of rat stomach in urethane anesthetized rats. Control gastric acid output was obtained using 0.9% sodium chloride as perfusate and extract induced gastric acid output was obtained by perfusion with 0.1% solution of Anacardium occidentale Intragastric administration of the extract caused significant increase in mean gastric output (P <0.05). Atropine (5MUg/100g,) lM and Cimetidine (5mg/100g), IM. significantly inhibited the extract induced gastric acid secretion via muscarinic and histaminic receptors respectively. Our findings showed that the use of the plant extract as a single anti-gastric ulcer therapy may not involve lowering of acid secretions rather it may be due to its anti Helicobacter pylori effect. PMID- 22314905 TI - Effect of aqueous extract of Phyllantus amarus leaves on implantation and pregnancy in rats. AB - Phyllanthus amarus is a medicinal plant used widely in the treatment of many diseases. It has a long tradition of use in the Hindu Ayurvedic system of medicine and it has long been used as a medicinal agent in cultures around the world. Traditionally, in the Yoruba speaking part of western Nigeria it is used in treating sterility and difficult childbirth. This experiment was therefore designed to scientifically test the effect of aqueous extract of Phyllanthus amarus (AEPA) leaves on implantation and pregnancy. Animals were divided into two groups of 18 rats each after pregnancy has been established. Group I received 0.2mg/100g body weight of AEPA from day 1 of pregnancy. Group II received equal volume of distilled water serving as the control. Six rats from each group were sacrificed on days 6, 8 and 19 respectively. Implantation and pregnancy were assessed. AEPA reduced the time frame for implantation in the treated rats and caused abortion of pregnant rats. Although the aqueous extract of Phyllanthus amarus reduces the time frame for implantation, its abortificent effect does not support the traditional claim that it can treat sterility. PMID- 22314906 TI - Effect of diet of varying protein concentrations on the activity of erythrocyte membrane Ca2+Mg2+ ATPase in dogs. AB - Alterations in protein diet have been reported to result in alterations in calcium homeostasis in the body. Ca2+Mg2+ATPase is an ubiquitous enzyme important in calcium homeostasis in the body. The effect of varying protein diet on the activities of Ca2+ pump across cell membranes is however yet to be fully elucidated. In this study, the activity of erythrocyte membrane calcium pump in response to varying protein concentration in diet was therefore studied in the dog. The study was carried out in 24 dogs, randomly divided into 4 groups. The groups were fed with diets containing 30%, 26%, 16% and 0% proteins (high, medium, low and zero) for six weeks respectively. Blood samples were collected from each animal to determine packed cell volumes, hematocrit, blood urea, electrolyte studies and erythrocyte ghost membrane studies. The effects of Ca2+ and ATP on the activity of Ca2+Mg2+ ATPase were determined in the isolated ghost membrane. The result of the study shows that there was a protein diet dependent increase in the activity of Ca2+Mg2+ ATPase in the presence and absence of ATP in all the groups with the highest activity recorded in the high protein diet group and the lowest activity observed in the zero protein group. There was also a protein diet dependent increase in the protein concentration of the membranes in all groups observed with the highest protein concentration recorded in the high protein diet group and the lowest activity observed in the zero protein group. There was a significant decrease in K+ concentration (P <0.05) and a significant increase in urea concentration of animals fed with high protein diet (P <0.05). There was also a significant increase (P <0.05) in HCO3- concentration in the animals fed with medium protein diet and no significant difference in the PCV and heamatocrit values in all groups. This study has shown that high protein diets increase the activity of the Ca2+Mg2+ ATPase in the presence and absence of ATP. PMID- 22314907 TI - Effect of increased dietary calcium on body weight, food and water intake in oral contraceptive treated female rats. AB - The effects of high calcium diet on body weight in OC treated rats are unknown. This study therefore investigated the effect of increasing dietary calcium from 0.9% to 2.5% on body weight, food ingestion, water intake, heart weight index and renal weight index in female Sprague-Dawley rats treated with a combination of OC steroids (ethinyloestradiol + norgestrel). The rats were assigned into three groups of average of 11 rats each; control, OC-treated and OC + Calcium – treated groups and administered orally for 10 weeks. Food and water intake, body weight, cardiac weight index, left ventricular weight index, renal weight index and serum calcium level were determined. The result shows that OC treated rats had significantly lower serum calcium concentration, body weight gain, food, water and calcium intake than those of the control rats. The OC + Calcium – treated rat had significantly higher serum calcium concentration, food, water and calcium intake but significantly lower body weight than those of the OC - treated rats. OC + Calcium - treated rats had significantly higher water intake, calcium intake and significantly lower body weight and food intake when compared with the control rats. Cardiac weight index and renal weight index was comparable in all groups. In conclusion, combined OC-induced reduction in weight gain might be associated with inhibition of the feeding center and consequent inhibition of the thirst center. Co-administration of dietary calcium augmented the reduction in weight gain seen in OC-treated rats probably by further suppression of the feeding and thirst centers. PMID- 22314908 TI - Effects of oral administration of nicotine on organ weight, serum testosterone level and testicular histology in adult male rats. AB - This study investigated the effects of oral administration of nicotine on body and reproductive organ weight, serum testosterone level and testicular histology in adult male rats. Forty male rats divided into five groups and treated for a period of 30 days with 0.5mg/kg (low dose) and 1.0 mg/kg (high dose) body weight of nicotine while the control rats received 0.2 ml/kg normal saline. The fourth and fifth groups were gavaged with 0.5mg/kg and 1.0mg/kg body weight of nicotine but were left untreated for another 30 days. These groups served as the recovery groups. At the end of each experimental period, the animals were scarified and their reproductive organs were removed and weighed immediately. There was no significant change in the body weight. There was a significant decrease (p <0.05) in the testicular and epididymal weight of rats for both treatments while the decrease in the seminal vesicle weight for both treatment groups was not significant. The prostate weight was not significantly increased in both groups. The recovery groups showed appreciable recovery in their organ weight. Serum level of testosterone of both groups was significantly decreased in a dose dependent manner when compared with those of the control rats. The histological section showed testicular degeneration and disorganization in the cytoarchitecture, as the observed changes were pronounced in the high dose group than the low dose group. However, there were both regeneration of the germinal epithelium and restructuring of the interstitum towards normal in the recovery groups. No lesion was observed in the epididymis of the rats. The results suggest that nicotine has deleterious effect on the male reproductive organ of albino rats ameliorated by nicotine cessation. PMID- 22314909 TI - Hypoglycemic effect of methanolic extract of Anacardium occidentale leaves in alloxan-induced diabetic rats. AB - Anacardium occidentale Leave (Anacardiaceae), a plant natively grown in wastelands in Africa is used as a folk remedy for diabetes mellitus. Previous studies, reported the hypoglycemic effect of the aqueous leaf extract of A. occidentale in diabetic rats and its prophylactic activity against the diabetogenic action of streptozotocin This study evaluated the hypoglycemic effect of a methanolic extract of streptozotocin leaves and its fractions in Alloxan-induced diabetic rats in comparison to Tolbutamide, a reference drug. For moderately diabetic rat, A. occidentale caused a 79.2 % change over 4 hours and Tolbutamide caused a 63.1 % change over this same time period. When the rat were considered to be severely diabetic, the A. occidentale decreased the blood glucose levels by 20.8% change over four hours and the mean percent change over 4 hours for Tolbutamide was 47.63%. These values were not considered significant. So the same conclusion can be made about the efficacy of A. occidentale, when compared to the reference drug, Tolbutamide. These results that show that A. occidentale has a similar ability compared with Tolbutamide to lower blood glucose levels. PMID- 22314910 TI - Hydrostatic and osmotic pressure study of the RNA hydration. AB - The tertiary structure of nucleic acids results from an equilibrium between electrostatic interactions of phosphates, stacking interactions of bases, hydrogen bonds between polar atoms and water molecules. Water interactions with ribonucleic acid play a key role in its structure formation, stabilization and dynamics. We used high hydrostatic pressure and osmotic pressure to analyze changes in RNA hydration. We analyzed the lead catalyzed hydrolysis of tRNAPhe from S. cerevisiae as well as hydrolytic activity of leadzyme. Pb(II) induced hydrolysis of the single phosphodiester bond in tRNAPhe is accompanied by release of 98 water molecules, while other molecule, leadzyme releases 86. PMID- 22314911 TI - Tanshinone IIA protects PC12 cells from beta-amyloid(25-35)-induced apoptosis via PI3K/Akt signaling pathway. AB - For the aging populations of any nation, Dementia is becoming a primary problem and Alzheimer's dementia (AD) is the most common type. However, until now, there is no effective treatment for AD. Tanshinone IIA (Tan IIA) has been reported for neuroprotective potential to against amyloid beta peptides (Abeta)-induced cytotoxicity in the rat pheochromocytoma cell line PC-12, which is widely used as AD research model, but the mechanism still remains unclear. To investigate the effect of Tan IIA and the possible molecular mechanism in the apoptosis of PC12 cells, we induced apoptosis in PC12 cells with beta-amyloid(25-35), and treated cells with Tan IIA. After 24 h treatment, we found that Tan IIA increased the cell viability and reduced the number of apoptotic cells induced by Abeta(25-35). However, neuroprotection of Tan IIA was abolished by PI3K inhibitor LY294002. Meanwhile, Treatment with lithium chloride, a phosphorylation inhibitor of GSK3beta, which is a downstream target of PI3K/Akt, can block Abeta(25-35) induced cell apoptosis in a Tan IIA-like manner. Our findings suggest that Tan IIA is an effective neuroprotective agent and a viable candidate in AD therapy and PI3K/Akt activation and GSK3beta phosphorylation are involved in the neuroprotection of Tan IIA. PMID- 22314912 TI - XPA A23G polymorphism and susceptibility to cancer: a meta-analysis. AB - Xeroderma pigmentosum group A (XPA) participates in modulating recognition of DNA damage during the DNA nucleotide excision repair process. The XPA A23G polymorphism has been investigated in case-control studies to evaluate the cancer risk attributed to the variant, but the results were conflicting. To clarify the effect of XPA A23G polymorphism in cancer risk, we conducted a meta-analysis that included 30 published case-control studies. Overall, no significant association of XPA A23G variant with cancer susceptibility was observed for any genetic model. However, significant association was observed for colorectal cancer (GG vs. AA: OR = 1.68, 95% CI = 1.15-2.44; dominant genetic model GG + AG vs. AA: OR = 1.54, 95% CI = 1.08-1.17), for breast cancer an increased but non-significant risk was found (GG vs. AA: OR = 1.27, 95% CI = 0.98-1.66; dominant genetic model GG + AG vs. AA: OR = 1.27, 95% CI = 0.99-1.63), and for head and neck cancer an increased risk was observed in recessive model (OR = 1.19, 95% CI = 1.02-1.38), whereas for lung cancer a significant reduced risk was observed (GG vs. AA: OR = 0.77, 95% CI = 0.66-0.90; dominant genetic model GG + AG vs. AA: OR = 0.76, 95% CI = 0.66-0.87), it's noting that in Asian population the inverse association was more apparent. In addition, in Asian population for esophageal cancer a significant decreased risk was also found in dominant genetic model (OR = 0.55; 95% CI = 0.43-0.70) and for head and neck cancer an increased risk was observed in dominant genetic model (OR = 1.51, 95% CI = 1.03-2.23). The meta-analysis suggested that the XPA A23G G allele is a low-penetrant risk factor for cancer development. PMID- 22314913 TI - Characterization and expression analysis of a trypsin-like serine protease from planarian Dugesia japonica. AB - Trypsin-like serine proteases are involved in large number of processes, especially in digestive degradation and immune responses. Here, we identify the characterization of a trypsin-like serine protease in planarian, Djtry, which interestingly has the incompletely conserved catalytic triad (K, D, and S). Phylogenetic analysis suggests that Djtry is an ancient type of trypsin-like serine proteases. The spatial and temporal expression patterns of Djtry are shown during regenerating and embryonic development by whole-mount in situ hybridization. Djtry is found to display a tissue specific expression pattern, with a predominant expression detected in whole gut region of intact and regenerating planarian. While the tissue- and stage-specific expression patterns during the embryonic development imply the roles of Djtry involve in yolk degradation and gut formation. Quantitative real-time PCR was carried out to analyze the function of this protease in vivo after planarians were stimulated to a bacterial challenge and food. The results showed that Djtry increased after a bacterial challenge and was basically stable for food. Therefore, the trypsin like serine protease might be involved in the innate defense reactions against bacterial infection. PMID- 22314914 TI - Induction of antioxidative Nrf2 gene transcription by coffee in humans: depending on genotype? AB - The Nrf2/ARE pathway is a major cellular defense mechanism that prevents damage by reactive oxygen species through induction of antioxidative phase II enzymes. However, the activity of the Nrf2/ARE system is not uniform with variability in response presumed to be dependent on the Nrf2 genotype. We recently completed a pilot human coffee intervention trial with healthy humans, where large interindividual differences in the antioxidative response to the study coffee were examined. Here, we address the question whether differences in the modulation of Nrf2 gene transcription, assessed as an induction of Nrf2 gene transcription by Q-PCR, might be correlated with specific Nrf2 genotypes. To date, nine single nucleotide polymorphisms (SNPs) have been identified in the Nrf2 (NFE2L2) gene. Two of these, the -617C/A and -651G/A SNPs are located within the promoter region and have previously been reported to influence the activity of the Nrf2/ARE pathway by reducing Nrf2 transcriptional activity. Sequencing of the critical Nrf2 gene promoter region not only confirmed the existence of these SNPs within the participants of the trial at the expected frequency (33% carrying the -617C/A, 17% the -651G/A and 56% the -653A/G SNP) but also indicated reduced Nrf2 gene transcription associated with a normal diet if the SNPs at position 617, -651 or -653 were present. Of note, the data also indicated the study coffee increased Nrf2 gene transcription even in SNP carriers. This further highlights the relevance of genotype-dependent induction of Nrf2 gene transcription that appears to be largely influenced by dietary factors. PMID- 22314915 TI - Effect of the calcium sensing receptor on rat bone marrow-derived mesenchymal stem cell proliferation through the ERK1/2 pathway. AB - Migration and proliferation of bone marrowderived mesenchymal stem cells (BMSCs) is critical to treatment of ischemic injury. The calcium sensing receptor (CaSR) has an important role in maintaining systemic calcium homeostasis, which is related to cell proliferation, apoptosis and paracrine signaling. We hypothesize that CaSR may enhance BMSC proliferation. Rat BMSCs were incubated with various calcium concentrations for 48 h in vitro to activate CaSR. To investigate potential mechanisms responsible for growth enhancement by calcium, the rat BMSC cell cycle progression was analyzed by fluorescence-activated cell sorting (FACS), and induction of apoptosis confirmed by cytofluorimetric analysis using propidium iodide and Annexin V-FITC double staining. Since the mitogen-activated protein kinase (MAPK) signaling pathway was one of the most significantly affected by CaSR, MAPK activation was measured by western blotting. Calcium exposure significantly enhanced rat BMSCs proliferation, as well as the proportion of the population in S phase, in a dose-dependent manner, effects which were abolished by NPS2390 (a CaSR antagonist) and U0126 (a MEK1/2 inhibitor). These results demonstrate that CaSR is involved in rat BMSC proliferation, as seen by an increased proliferation index, decreased apoptosis, and ERK1/2 activation, and provide important insight into the cellular and molecular mechanisms by which CaSR affects cell proliferation. A CaSR agonist may prove useful to enhance BMSC survival during transplantation. PMID- 22314916 TI - Expression of a2, a5 and a6 subunits of integrin in de-differentiated NIH3T3 cells by cell-free extract of embryonic stem cells. AB - Generation of patient specific stem cells is among the ultimate goals in regenerative medicine. Such a cell needs to be functional when it transplants. Interaction between the matrix proteins and integrin adjust many cells' function such as adhesion, migration, cell cycle and self renewal in stem cells. In this study, NIH3T3 cells were dedifferentiated by mouse Embryonic Stem Cell (mESC) extract. The expression of pluripotency markers as well as a2, a5 and a6 integrin subunits were determined. NIH3T3 cells treated with mESC extract showed noticeable changes in cell morphology as early as day 2 post-treatment forming colonies similar to typical mESC morphology by day 8, after three passages. Alkaline phosphatase (ALP) assay and immunocytochemistry staining were performed for the induced reprogrammed cells. The results indicated that these colonies showed the ALP activity and they express Sox2 and Nanog. RT-PCR revealed that the colonies also express Oct3/4. NIH3T3 cells, ESC and reprogrammed cells expressed a2 integrin. a5 integrin expression was greatest in reprogrammed cells followed by the expression of this integrin in NIH3T3 which in turn was more than in ESC. a6A integrin was expressed in NIH3T3 cells while a6B integrin was expressed in ESC and in very low quantity was expressed in reprogrammed cells. These data provide evidence for both the generation of ES like cells from differentiated somatic cells and the expression profile of integrins after de-differentiation by mESC extract. PMID- 22314917 TI - A phosphonated triarylmethyl radical as a probe for measurement of pH by EPR. AB - A new water soluble phosphonated tetrathiatriarylmethyl radical has been synthesized and its application for pH measurement in a physiological range by EPR is reported. PMID- 22314918 TI - Transient increases in dendritic spine density contribute to dentate gyrus long term potentiation. AB - Dendritic spines are the primary sites for excitatory neurotransmission in the adult brain and exhibit changes in their number and morphology with experience. The relationship between spine formation and synaptic activity has been best characterized along the apical dendrites of pyramidal neurons in the hippocampal CA1 subfield. However, less is known about the structural mechanisms at the spine that mediate plasticity in other hippocampal subfields. The dentate gyrus is the predominant point of entry for synaptic input to the hippocampus, and dentate granule cells differ from CA1 pyramidal neurons in terms of their morphology and biophysical properties. In order to understand the structural mechanisms for plasticity in the dentate gyrus, we measured dendritic spine density in hippocampal slice preparations at different intervals following synaptic stimulation. We observed that transient increases in dendritic spine density are detectable 30 min after induction of long-term potentiation (LTP). By 60 min poststimulation, dendritic spine density has returned to basal levels. Both early LTP and enhancements in dendritic spine density could be blocked by destabilizing actin filaments, but not by inhibitors of transcription or protein synthesis. These results indicate that spine formation is a transient event that is required for dentate gyrus LTP. PMID- 22314919 TI - Postoperative validation of bone-anchored implants in the single-sided deafness population. AB - OBJECTIVE: The purpose of this study was to present objective and subjective outcomes on speech-in-noise testing as a predictor of patient performance after bone-anchored implant surgery in patients with single-sided deafness (SSD). DESIGN: Retrospective review of adult subjects who received bone-anchored implants for the indication of SSD comparing results on speech-in-noise measures in the unaided condition to postoperative aided condition using the patient's external bone-anchored implant processor as a validation of device performance. SETTING: Tertiary referral center providing outpatient surgical and audiologic care. PATIENTS: Adult English speaking subjects with SSD who underwent bone anchored implantation between 2005 and 2010. INTERVENTION: Subjects were evaluated with speech-in-noise measures in the sound field using a 90/270 speaker configuration in both the unaided and aided implant condition for validation of implant performance. Subjective benefit was evaluated using the Glasgow Hearing Aid Benefit Profile. MAIN OUTCOME MEASURES: Outcome measures included signal-to noise ratio (SNR) loss and word recognition ability in noise as measured using the QuickSIN and the Glasgow Hearing Aid Benefit Profile. RESULTS: A significant improvement in speech-in-noise measures was noted in the postoperative aided condition when compared with the unaided condition (Wilcoxon signed-rank test, p < 0.0001). Significant decrease in disability postoperatively also was observed (Wilcoxon signed-rank test, p < 0.001). Positive associations were observed for postoperative aided SNR loss and benefit, satisfaction, and use. Passing-Bablok regression analysis showed the preoperative and postoperative results to be statistically equivalent. CONCLUSION: The results support the use of speech-in noise measures as an accurate postimplantation assessment of overall benefit in patients with SSD. SNR loss is a good predictor of postoperative subjective benefit and satisfaction. PMID- 22314920 TI - Assessment of sound quality perception in cochlear implant users during music listening. AB - BACKGROUND: Although cochlear implant (CI) users frequently report deterioration of sound quality when listening to music, few methods exist to quantify these subjective claims. OBJECTIVE: 1) To design a novel research method for quantifying sound quality perception in CI users during music listening; 2) To validate this method by assessing one attribute of music perception, bass frequency perception, which is hypothesized to be relevant to overall musical sound quality perception. HYPOTHESIS: Limitations in bass frequency perception contribute to CI-mediated sound quality deteriorations. The proposed method will quantify this deterioration by measuring CI users' impaired ability to make sound quality discriminations among musical stimuli with variable amounts of bass frequency removal. METHOD: A method commonly used in the audio industry (multiple stimulus with hidden reference and anchor [MUSHRA]) was adapted for CI users, referred to as CI-MUSHRA. CI users and normal hearing controls were presented with 7 sound quality versions of a musical segment: 5 high pass filter cutoff versions (200-, 400-, 600-, 800-, 1000-Hz) with decreasing amounts of bass information, an unaltered version ("hidden reference"), and a highly altered version (1,000-1,200 Hz band pass filter; "anchor"). Participants provided sound quality ratings between 0 (very poor) and 100 (excellent) for each version; ratings reflected differences in perceived sound quality among stimuli. RESULTS: CI users had greater difficulty making overall sound quality discriminations as a function of bass frequency loss than normal hearing controls, as demonstrated by a significantly weaker correlation between bass frequency content and sound quality ratings. In particular, CI users could not perceive sound quality difference among stimuli missing up to 400 Hz of bass frequency information. CONCLUSION: Bass frequency impairments contribute to sound quality deteriorations during music listening for CI users. CI-MUSHRA provided a systematic and quantitative assessment of this reduced sound quality. Although the effects of bass frequency removal were studied here, we advocate CI-MUSHRA as a user friendly and versatile research tool to measure the effects of a wide range of acoustic manipulations on sound quality perception in CI users. PMID- 22314921 TI - An unexpected third window in a case of advanced cavitating otosclerosis. PMID- 22314922 TI - Surgical approach for treatment of carcinoma of the anterior wall of the external auditory canal. AB - OBJECTIVE: Treatment outcomes for carcinomas of the external auditory canal (EAC) were evaluated regarding radiologic and pathologic factors. STUDY DESIGN: Retrospective case review. SETTING: University hospital. PATIENTS: Fifteen patients histologically diagnosed with carcinomas of the EAC. INTERVENTION: A radiologic and pathologic analysis was performed on these patients histologically diagnosed with carcinomas of the EAC and treated surgically at our institution. We evaluated the size of focal defects in the anteroinferior (AI) canal wall of the tympanic bone with preoperative computed tomographic (CT) scans. Histopathologic slides for the same patients were evaluated according to the same criteria as the CT scans. MAIN OUTCOME MEASURE: Pathologic features and estimated survival rate. RESULTS: Preoperative CT scans of 15 temporal bones demonstrated an AI canal wall defect ranging from less than 1 mm to full-thickness destruction. Six of 15 patients had an AI canal wall defect greater than 2 mm on preoperative CT scan. Pathologic findings in these 6 cases showed extension of the tumor through the AI defect into the anterior soft tissues. Information on patients' survival status was obtained after a median follow-up period of 78.3 months (range, 18-151 mo). CONCLUSION: Preoperative CT can be used to accurately determine the pathologic extent of tumor invasion in carcinomas of the EAC. This diagnostic method facilitates exchange of accurate clinical data in a comparable form and can be used to evaluate the efficacy of existing and proposed treatments for EAC tumors. PMID- 22314923 TI - Osteopetrosis of the temporal bone. PMID- 22314924 TI - Magnetic resonance imaging fails to show evidence of reduced endolymphatic hydrops in gentamicin treatment of Meniere's disease. AB - OBJECTIVE: To verify the hypothesis that intratympanic (IT) gentamicin (Gent) treatment in Meniere's disease (MD) is capable of reducing endolymphatic hydrops (EH), as evaluated by 3-dimensional fluid-attenuated inversion recovery (3D FLAIR) sequence in a 3-Tesla magnetic resonance imaging (MRI) unit, after IT gadolinium administration. PATIENTS: A total of 8 patients (5 men and 3 women; aged 40-78 yr; median, 60 yr) with definite MD participated in the investigation. The duration of the disease ranged from 1 to 10 years (median, 4 yr), with a prevalence of vertigo spells of 1 to 6 per month (median, 3.1), as calculated in the last 6 months. INTERVENTION: A 3D-FLAIR MRI was performed 24 hours after IT injection of diluted gadobutrol. Intratympanic Gent injection was performed in a period variable from 1 to 3 weeks after 3D-FLAIR MRI. A single-shot administration protocol was attempted with additional injections administered on demand in the case of relapsing vertigo spells. MRI was repeated after 3 to 12 months (median, 8 mo) after treatment. MAIN OUTCOME MEASURE: The degree and extension of EH as evaluated by 3D-FLAIR MRI was compared from images obtained pre- and post-ITGent administration. RESULTS: After ITGent administration, 4 patients did not show any MRI modification, 3 patients showed a worsening of EH in one site, and 1 patient showed a worsening in two sites. No subjects presented reduction of EH. CONCLUSION: No evidence of reduced EH following ITGent treatment has been shown in the present imaging investigation. PMID- 22314925 TI - Exploring salivary proteomes in edentulous patients with type 2 diabetes. AB - Type 2 diabetes and tooth loss are linked both epidemiologically and pathophysiologically. We applied label-free differential protein expression analysis using multidimensional liquid chromatography/tandem mass spectrometry (2D-LC-MS/MS) to explore the proteomic profile of saliva samples collected from selected type 2 diabetic edentulous patients and non-diabetic controls. Ninety six peptides corresponding to 52 proteins were differentially expressed between the diabetic edentulous patients and controls (p < 0.05). Some diabetes-related inflammatory biomarkers including glyceraldehyde-3-phosphate dehydrogenase and serum amyloid A were detected with levels increased in diabetic samples. Other biomarkers including amylase, palate, lung and nasal epithelium associated protein (PLUNC), and serotransferrin levels were decreased in diabetic samples. In contrast with previous findings, salivary carbonic anhydrase 6 and alpha-2 macroglobulin levels, however, were decreased in this diabetic patient population. Cluster analysis and principle component analysis demonstrated a differential pattern of protein biomarker expression between diabetic and control subjects. Western blot analysis was completed to confirm the relatively lower expression level of two biomarkers, including PLUNC and amylase in the diabetic group compared to control subjects. The presence of salivary biomarkers specific for diabetes in edentulous subjects mimics those in serum, especially those related to inflammatory/lipid metabolism. While this exploratory study requires further validation with a larger population, it provides proof-of-principle for salivary proteomics for edentulous subjects with diabetes. PMID- 22314926 TI - Ruthenium(II) polypyridyl complexes and DNA--from structural probes to cellular imaging and therapeutics. AB - In the last few decades, coordination complexes based on d(6) metal centres and polypyridyl ligand architectures been developed as structure- and site-specific reversible DNA binding agents. Due to their attractive photophysical properties, much of this research has focused on complexes based on ruthenium(II) centres and, more recently, attention has turned to the use of these complexes in biological contexts. As the rules that govern the cellular uptake and cellular localisation of such systems are determined they are finding numerous applications ranging from imaging to therapeutics. This review illustrates how the interdisciplinary nature of this research-which takes in synthetic chemistry, biophysical and in cellulo studies-makes this an exciting area in which an array of further applications are likely to emerge. PMID- 22314927 TI - Polymer microarrays for high throughput discovery of biomaterials. AB - The discovery of novel biomaterials that are optimized for a specific biological application is readily achieved using polymer microarrays, which allows a combinatorial library of materials to be screened in a parallel, high throughput format (1). Herein is described the formation and characterization of a polymer microarray using an on-chip photopolymerization technique (2). This involves mixing monomers at varied ratios to produce a library of monomer solutions, transferring the solution to a glass slide format using a robotic printing device and curing with UV irradiation. This format is readily amenable to many biological assays, including stem cell attachment and proliferation, cell sorting and low bacterial adhesion, allowing the ready identification of 'hit' materials that fulfill a specific biological criterion (3-5). Furthermore, the use of high throughput surface characterization (HTSC) allows the biological performance to be correlated with physio-chemical properties, hence elucidating the biological material interaction (6). HTSC makes use of water contact angle (WCA) measurements, atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). In particular, ToF-SIMS provides a chemically rich analysis of the sample that can be used to correlate the cell response with a molecular moiety. In some cases, the biological performance can be predicted from the ToF-SIMS spectra, demonstrating the chemical dependence of a biological-material interaction, and informing the development of hit materials (5,3). PMID- 22314928 TI - Is apparent diffusion coefficient reliable and accurate for monitoring effects of antiangiogenic treatment in a longitudinal study? AB - PURPOSE: To evaluate the reliability and accuracy of the apparent diffusion coefficient (ADC) for monitoring antiangiogenic treatment in a longitudinal study. MATERIALS AND METHODS: Tumor volume and ADC were monitored by T2-weighted magnetic resonance imaging (MRI) and diffusion-weighted MRI, respectively, in 18 mice with angiogenesis-dependent tumors (U118MG) before (day 0) and after 2, 7, 14, and 21 days of administration of the antiangiogenic agent sunitinib maleate (n = 12) or vehicle (n = 6). Percent changes in tumor volume and ADC were calculated and correlations between tumor volume and ADC were evaluated. RESULTS: Tumor volume and ADC showed a negative correlation at 69 of the 72 (96%) follow up measurements. In the 13 mice with tumor regrowth, ADC started to decrease before (27%) or at the same time (73%) as tumor regrowth. Pretreatment ADC and percent change in ADC change on days 0-2 were similar in mice with positive and negative responses to treatment (0.851 vs. 0.999, 24% vs. 16%). Percent change of ADC showed significant negative correlation with percent change in tumor volume in both the control (r = -0.69) and treated (r = -0.65) groups. CONCLUSION: Percent change in ADC is a reliable and accurate marker for monitoring the effects of antiangiogenic treatment, whereas pretreatment ADC and early changes in ADC (ie, days 0-2) are limited in predicting treatment outcome. PMID- 22314929 TI - Therapeutics in Huntington's Disease. AB - OPINION STATEMENT: There is no specific treatment for Huntington's disease (HD). Its many symptoms of motor, psychiatric, and cognitive deterioration are managed with symptomatic relief, rehabilitation, and support. The only drug approved by the US Food and Drug Administration (FDA) for the treatment of HD is an antichoreic agent, tetrabenazine, but this drug is used sparingly because of uneasiness regarding its propensity to cause depression and suicidality in this population, which is already at risk for these complications. Neuroleptics are still first-line treatments for chorea accompanied by comorbid depression and/or behavioral or psychotic symptoms, as is often the case. Psychiatric features, which have a significant impact on a patient's professional and personal life, often become the major focus of management. In addition to neuroleptics, commonly used medications include antidepressants, mood stabilizers, anxiolytics, and psychostimulants. In contrast, few treatment options are available for cognitive impairment in HD; this remains an important and largely unmet therapeutic need. HD patients typically lack insight into their disease manifestations, failing to recognize their need for treatment, and possibly even arguing against it. Multipurpose medications are employed advantageously to simplify the medication regimen, so as to facilitate compliance and not overwhelm the patient. For example, haloperidol can be prescribed for a patient with chorea, agitation, and anorexia, rather than targeting each symptom with a different drug. This approach also limits the potential for adverse effects, which can be difficult to distinguish from the features of the disease itself. With HD's complexity, it is best managed with a multidisciplinary approach that includes a movement disorders specialist, a genetic counselor, a mental health professional, a physical therapist, and a social worker for support and coordination of services. As the disease progresses, there may be need for other specialists, such as a speech and occupational therapist, a nutritionist for weight loss, and ultimately, a palliative care specialist. PMID- 22314931 TI - The condensed chromatin fiber: an allosteric chemo-mechanical machine for signal transduction and genome processing. AB - Allostery is a key concept of molecular biology which refers to the control of an enzyme activity by an effector molecule binding the enzyme at another site rather than the active site (allos = other in Greek). We revisit here allostery in the context of chromatin and argue that allosteric principles underlie and explain the functional architecture required for spacetime coordination of gene expression at all scales from DNA to the whole chromosome. We further suggest that this functional architecture is provided by the chromatin fiber itself. The structural, mechanical and topological features of the chromatin fiber endow chromosomes with a tunable signal transduction from specific (or nonspecific) effectors to specific (or nonspecific) active sites. Mechanical constraints can travel along the fiber all the better since the fiber is more compact and regular, which speaks in favor of the actual existence of the (so-called 30 nm) chromatin fiber. Chromatin fiber allostery reconciles both the physical and biochemical approaches of chromatin. We illustrate this view with two supporting specific examples. Moreover, from a methodological point of view, we suggest that the notion of chromatin fiber allostery is particularly relevant for systemic approaches. Finally we discuss the evolutionary power of allostery in the context of chromatin and its relation to modularity. PMID- 22314930 TI - Red Blood Cell Transfusion and Transfusion Alternatives in Traumatic Brain Injury. AB - OPINION STATEMENT: Anemia develops in about 50% of patients hospitalized with traumatic brain injury (TBI) and is recognized as a cause of secondary brain injury. This review examines the effects of anemia and transfusion on TBI patients through a literature search to identify original research on anemia and transfusion in TBI, the effects of transfusion on brain physiology, and the role of erythropoietin or hemoglobin-based blood substitutes (HBBSs). However, the amount of high-quality, prospective data available to help make decisions about when TBI patients should be transfused is very small. Randomized transfusion trials have involved far too few TBI patients to reach definitive conclusions. Thus, it is hardly surprising that there is widespread practice variation. In our opinion, a hemoglobin transfusion threshold of 7 g/dL cannot yet be considered safe for TBI patients admitted to hospital, and in particular to the ICU, as it is for other critically ill patients. Red blood cell transfusions often have immediate, seemingly beneficial effects on cerebral physiology, but the magnitude of this effect may depend in part upon how long the cells have been stored before administration. In light of existing physiological data, we generally aim to keep hemoglobin concentrations greater than 9 g/dL during the first several days after TBI. In part, the decision is based on the patient's risk of or development of secondary ischemia or brain injury. An increasing number of centers use multimodal neurologic monitoring, which may help to individualize transfusion goals based on the degree of cerebral hypoxia or metabolic distress. When available, brain tissue oxygen tension values less than 15-20 mm Hg or a lactate:pyruvate ratio greater than 30-40 would influence us to use more aggressive hemoglobin correction (e.g., a transfusion threshold of 10 g/dL). Clinicians can attempt to reduce transfusion requirements by limiting phlebotomy, minimizing hemodilution, and providing appropriate prophylaxis against gastrointestinal hemorrhage. Administration of exogenous erythropoietin may have a small impact in further reducing the need for transfusion, but it also may increase complications, most notably deep venous thrombosis. Erythropoietin is currently of great interest as a potential neuroprotective agent, but until it is adequately evaluated in randomized controlled trials, it should not be used routinely for this purpose. HBBSs are also of interest, but existing preparations have not been shown to be beneficial-or even safe-in the context of TBI. PMID- 22314934 TI - Antitumor effect of vascular endothelial growth factor inhibitor sunitinib in preclinical models of hepatocellular carcinoma. AB - OBJECTIVE: Tumor recurrence and metastasis is the most common cause of mortality in hepatocellular carcinoma (HCC) patients. Despite positive results with vascular endothelial growth factor (VEGF) inhibitors in preclinical studies using HCC xenograft models, the clinical outcome in HCC patients has been disappointing. So far, only the multitargeted tyrosine kinase inhibitor sorafenib has been shown to significantly improve survival in HCC patients, suggesting that this class of agents could be effective against HCC. Recently, another VEGF inhibitor, sunitinib, showed survival benefits in HCC hepatitis B-positive patients, but failed to improve survival in HCC hepatitis C-positive patients. Obviously, concomitant liver disease, liver function in general, and the local liver environment have a huge impact on treatment outcomes. In this study, we aimed to examine the antiproliferative effect of sunitinib in different HCC cell lines in vitro, and then in xenograft and orthotopic models of HCC in order to assess the effect of the local liver vasculature on drug efficacy. METHODS: Human cancer cell lines Huh7.5, Hep3B, and SK-Hep-1 were used for in-vitro studies. In in-vivo studies, each mouse carried Huh7.5 cells in both the subcutaneous and the intrahepatic compartment; therefore, drug exposure and treatment regimen were identical in both tumors. RESULTS: Sunitinib has the potential to moderately inhibit proliferation in the Huh7.5 cell line, induce p53 in the p53-wild-type cell line SK-hep-1, and to increase the S-phase and the sub-G1 component of the cell cycle in the Hep3B cell line. Diverse responses to sunitinib in HCC cell lines emphasize the heterogeneity of HCC tumors and may further explain the discrepancy between preclinical and clinical results. The in-vivo results show that sunitinib treatment was far less effective against intrahepatic tumors compared with xenografts. Histological data indicate that large solid intrahepatic tumors are severely affected by sunitinib as shown by large areas of necrosis and diminished number of viable tumor cells. CONCLUSION: The real problem when treating intrahepatic tumors with sunitanib and/or other VEGF inhibitors seems to arise from unopposed local growth of the small tumors and perhaps the development of distant micrometastases. Even though both xenograft and orthotopic models have limitations, these models add value to our understanding of tumor biology and help to better design treatment paradigms for patients with HCC. In comparison with xenograft models, the orthotopic HCC model allows for a more realistic assessment of drug efficacy in patients, in particular by enhancing our knowledge of the role that organ vasculature plays in the development of local metastasis and tumor resistance to antiangiogenic treatments. PMID- 22314935 TI - Isolation and characterization of a lytic Myoviridae bacteriophage PAS-1 with broad infectivity in Aeromonas salmonicida. AB - To search for candidate control agents against Aeromonas salmonicida subsp. salmonicida infections in aquaculture, one bacteriophage (phage), designated as PAS-1, was isolated from the sediment samples of the rainbow trout (Oncorhynchus mykiss) culture farm in Korea. The PAS-1 was morphologically classified as Myoviridae and possessed approximately 48 kb of double-strand genomic DNA. The phage showed broad host ranges to other subspecies of A. salmonicida as well as A. salmonicida subsp. salmonicida including antibiotic-resistant strains. Its latent period and burst size were estimated to be approximately 40 min and 116.7 PFU/cell, respectively. Furthermore, genomic and structural proteomic analysis of PAS-1 revealed that the phage was closely related to other Myoviridae phages infecting enterobacteria or Aeromonas species. The bacteriolytic activity of phage PAS-1 was evaluated using three subspecies of A. salmonicida strain at different doses of multiplicity of infection, and the results proved to be efficient for the reduction of bacterial growth. Based on these results, PAS-1 could be considered as a novel Aeromonas phage and might have potentiality to reduce the impacts of A. salmonicida infections in aquaculture. PMID- 22314936 TI - A pragmatic randomised controlled trial of the effectiveness and cost effectiveness of screening older women for the prevention of fractures: rationale, design and methods for the SCOOP study. AB - SCOOP is a UK seven-centre, pragmatic, randomised controlled trial with 5-year follow-up, including 11,580 women aged 70 to 85 years, to assess the effectiveness and cost-effectiveness of a community-based screening programme to reduce fractures. It utilises the FRAX algorithm and DXA to assess the 10-year probability of fracture. Introduction Osteoporotic, or low-trauma, fractures present a considerable burden to the National Health Service and have major adverse effects on quality of life, disability and mortality for the individual. Methods Given the availability of efficacious treatments and a risk assessment tool based upon clinical risk factors and bone mineral density, a case exists to undertake a community-based controlled evaluation of screening for subjects at high risk of fracture, under the hypothesis that such a screening programme would reduce fractures in this population. Results This study is a UK seven-centre, unblinded, pragmatic, randomised controlled trial with a 5-year follow-up period. A total of 11,580 women, aged 70 to 85 years and not on prescribed bone protective therapy will be consented to the trial by post via primary care providing 90% power to detect an 18% decrease in fractures. Conclusions Participants will be randomised to either a screening arm or control. Those undergoing screening will have a 10-year fracture probability computed from baseline risk factors together with bone mineral density measured by DXA in selected subjects. Individuals above an age-dependent threshold of fracture probability will be recommended for treatment for the duration of the trial. Subjects in the control arm will receive 'usual care'. Participants will be followed up 6 months after randomisation and annually by postal questionnaires with independent checking of hospital and primary care records. The primary outcome will be the proportion of individuals sustaining fractures in each group. An economic analysis will be carried out to assess cost-effectiveness of screening. A qualitative evaluation will be conducted to examine the acceptability of the process to participants. PMID- 22314937 TI - Online electrospray ionization mass spectrometric monitoring of protease catalyzed reactions in real time. AB - Although there are a lot of well established methods for monitoring enzyme catalyzed reactions, most of them are based on changes in spectroscopic properties during the conversion of substrates to products. However, reactions without optical changes are common, which are inapplicable to these spectroscopic methods. As an alternative technique for enzymologic research, mass spectrometry (MS) is favored due to its specificity, sensitivity, and the ability to obtain stoichiometric information. In this work, probe electrospray ionization (PESI) source coupled with a time of flight mass spectrometer was employed to monitor some typical protease-catalyzed reactions, including pepsinolysis and trypsinolysis of cytochrome c in real time. Due to the high electrical conductivity of each reaction system, corona discharges are likely to occur, which would decrease intensities of mass spectrometric signals. An ultra-fine sampling probe and an auxiliary vapor spray were adopted to prevent corona discharges. Experimental results from peptic and tryptic digestions of cytochrome c showed different and characteristic catalytic pathways. With the data presented in this study, PESI-MS can be considered as a potential tool for real-time monitoring of enzymatic reactions because of its simplicity in instrumental configuration, wide applicability under harsh conditions, and flexibility in combination with other techniques. PMID- 22314938 TI - Formation of a hydrogen-bonded heptazine framework by self-assembly of melem into a hexagonal channel structure. AB - Self-assembly of melem C(6)N(7)(NH(2))(3) in hot aqueous solution leads to the formation of hydrogen-bonded, hexagonal rosettes of melem units surrounding infinite channels with a diameter of 8.9 A. The channels are filled with strongly disordered water molecules, which are bound to the melem network through hydrogen bonds. Single-crystals of melem hydrate C(6)N(7)(NH(2))(3)?xH(2)O (x~2.3) were obtained by hydrothermal treatment of melem at 200 degrees C and the crystal structure (R 3c, a=2879.0(4), c=664.01(13) pm, V=4766.4(13)*10(6) pm(3), Z=18) was elucidated by single-crystal X-ray diffraction. With respect to the structural similarity to the well-known adduct between melamine and cyanuric acid, the composition of the obtained product was further analyzed by solid-state NMR spectroscopy. Hydrolysis of melem to cyameluric acid during syntheses at elevated temperatures could thus be ruled out. DTA/TG studies revealed that, during heating of melem hydrate, water molecules can be removed from the channels of the structure to a large extent. The solvent-free framework is stable up to 430 degrees C without transforming into the denser structure of anhydrous melem. Dehydrated melem hydrate was further characterized by solid-state NMR spectroscopy, powder X-ray diffraction, and sorption measurements to investigate structural changes induced by the removal of water from the channels. During dehydration, the hexagonal, layered arrangement of melem units is maintained whereas the formation of additional hydrogen bonds between melem entities requires the stacking mode of hexagonal layers to be altered. It is assumed that layers are shifted perpendicular to the direction of the channels, thereby making them inaccessible for guest molecules. PMID- 22314939 TI - Capsular Material of Cryptococcus neoformans: Virulence and Much More. AB - The capsule is generally considered one of the more powerful virulence factors of microorganisms, driving research in the field of microbial pathogenesis and in the development of vaccines. Cryptococcus neoformans is unique among the most common human fungal pathogens in that it possesses a complex polysaccharide capsule. This review focuses on the Cryptococcus neoformans capsule from the viewpoint of fungal pathogenesis, and the effective immune response target of the capsule's main component, glucuronoxylomannan. PMID- 22314940 TI - Effects of amphetamine on subcellular distribution of dopamine and DOPAC. AB - Amphetamine effects on distribution of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and amphetamine in vesicular, cytosolic, and extracellular compartments associated with a striatal varicosity were estimated through use of a computer simulation model. In addition, contribution to overall effects of amphetamine by each of five actions--transport by dopamine transporter (DAT), transport by vesicular monoamine transporter, stimulation of reverse transport, inhibition of monoamine oxidase (MAO), and slowing of dopamine cell firing rate--were evaluated. Amphetamine enters a varicosity almost entirely by DAT and accumulates to very high levels within the varicosity. Both reverse transport by DAT and passive diffusion contribute to continual amphetamine egress across the plasma membrane. Amphetamine enters storage vesicles by both transport and diffusion. The transport portion competes with dopamine storage, resulting in redistribution of approximately half of dopamine from vesicles to cytosol. The high concentration of amphetamine in the cytosol inhibits MAO, protecting cytosolic dopamine. A very small fraction of cytosolic dopamine is moved to extracellular compartment via reverse transport by DAT. The amount of dopamine moved by reverse transport is limited because of competition by very high cytosolic levels of amphetamine. In the presence of amphetamine, rate of dopamine transfer to extracellular compartment is less than control; however, high levels of extracellular dopamine are maintained because amphetamine occupies the DAT, thus limiting dopamine reuptake. Simulation output from a model using exchange diffusion mechanism of reverse transport does not match all published data that were simulated, suggesting that inward transport of a substrate is not required to initiate reverse transport. PMID- 22314941 TI - 'Achieving ensemble': communication in orthopaedic surgical teams and the development of situation awareness--an observational study using live videotaped examples. AB - Focused dialogue, as good communication between practitioners, offers a condition of possibility for development of high levels of situation awareness in surgical teams. This has been termed "achieving ensemble". Situation awareness grasps what is happening in time and space with regard to one's own unfolding work in relation to that of colleagues, and is necessary to maintain patient safety throughout a surgical list. We refined a typology, initially developed for use in studying the dynamics of teams in aviation safety, of 10 kinds of communication within two broad areas: 'Reports', or authoritative acts of communication setting up a monological or authoritative climate; and 'Requests', or facilitative acts of communication setting up a dialogical or participatory climate. We systematically mapped how orthopaedic surgical teams use verbal communication through analysis of videotaped operations using the typology. We asked: 'do orthopaedic surgical teams set up the conditions of possibility for the emergence of situation awareness through effective communication?' We found that orthopaedic surgical teams tend to produce monological rather than dialogical climates. Dialogue increases with more complex cases, but in routine work, communication levels are depressed and one-way, influenced by surgeons working within a traditionally hierarchical and authoritative culture. We suggest that such a monological climate inhibits development of situation awareness and then compromises patient safety. The same teams, however, generate potentially rich educational climates through exchange of profession-specific knowledge and skills, and we suggest that where technical skill exchange is good, non-technical or interpersonal communication skill levels can follow. PMID- 22314942 TI - Doctor-patient communication in Southeast Asia: a different culture? AB - Studies of doctor-patient communication generally advocate a partnership communication style. However, in Southeast Asian settings, we often see a more one-way style with little input from the patient. We investigated factors underlying the use of a one-way consultation style by doctors in a Southeast Asian setting. We conducted a qualitative study based on principles of grounded theory. Twenty residents and specialists and 20 patients of a low or high educational level were interviewed in internal medicine outpatient clinics of an Indonesian teaching hospital and two affiliated hospitals. During 26 weeks we engaged in an iterative interview and coding process to identify emergent factors. Patients were generally dissatisfied with doctors' communication style. The doctors indicated that they did not deliberately use a one-way style. Communication style appeared to be associated with characteristics of Southeast Asian culture, the health care setting and medical education. Doctor-patient communication appeared to be affected by cultural characteristics which fell into two broad categories representing key features of Southeast Asian culture, "social distance" and "closeness of relationships", and to characteristics categorized as "specific clinical context". Consideration of these characteristics could be helpful in promoting the use of a partnership communication style. PMID- 22314944 TI - Global climate change and body functions. AB - The following text is an excerpt of the Keynote Address delivered by Professor (Sir) A.C. Ugwu, of the University of Benin, at the Annual National Conference of the Physiological Society of Nigeria at Lagos, on Thursday, the 26th of August, 2010.In 1896, a Swedish Chemist, Savante Arrhenius, predicted Global Warming. Global Climate or Global W arming, is a gradual process that threatens sea level elevations, crop failure and famine, global rainfall patterns, changes to plant and animal populations and serious health effects.... PMID- 22314943 TI - The mouse forced swim test. AB - The forced swim test is a rodent behavioral test used for evaluation of antidepressant drugs, antidepressant efficacy of new compounds, and experimental manipulations that are aimed at rendering or preventing depressive-like states. Mice are placed in an inescapable transparent tank that is filled with water and their escape related mobility behavior is measured. The forced swim test is straightforward to conduct reliably and it requires minimal specialized equipment. Successful implementation of the forced swim test requires adherence to certain procedural details and minimization of unwarranted stress to the mice. In the protocol description and the accompanying video, we explain how to conduct the mouse version of this test with emphasis on potential pitfalls that may be detrimental to interpretation of results and how to avoid them. Additionally, we explain how the behaviors manifested in the test are assessed. PMID- 22314945 TI - Reproductive activities of female albino rats treated with quassin, a bioactive triterpenoid from stem bark extract of Quassia amara. AB - To evaluate the effect of quassin on female reproductive functions, 42 albino rats (35 females and 7 males) were used. The female albino rats were divided into seven groups of five rats each. Group I served as the control group and received distilled water while Groups II, III and IV rats were treatedorally with 0.1mg/kg, 1.0 mg/kg and 2.0 mg/kg body weight of quassin for 60 days respectively. Groups V, VI and VII rats were also treated orally with 0.1 mg/kg, 1.0mg/kg and 2.0 mg/kg body weight of quassin for 60 days but were left untreated for another 30 days, to serve as the recovery groups. At the end of each experimental period, blood samples were collected from each rat. Fertility study was done by cohabiting one untreated male with the five female rats in each group for 10 days. Quassin did not adversely affect the weight of the kidney, heart, liver and the body of the rats. However there was a significant decrease in the weight of the ovary and uterus in all the groups relative to the control. There was also a significant decrease in serum estrogen levels in quassin treated rats. The quassin treated rats had a significantly decreased mean litter number and weight. Histological studies show a disorganization and degeneration in the ovary while the uterus showed signs of vacuolation and disorganization. However, these effects were ameliorated after quassin was withdrawn from the rats. The results suggest that quassin has female anti-fertility properties, possibly acting via inhibition of estrogen secretion. PMID- 22314946 TI - Effects of bioactive principles from stem bark extract of Quassia amara, Quassin and 2-methoxycanthine-6-one, on haematological parameters in albino rats. AB - The effect of Quassia amara extract and two isolated compounds from the extract, quassin and 2-methoxycathine-6-one on haematological parameters was studied in rats. All doses of the extract and those of the quassin significantly increased red blood cell count, packed cell volume and haemoglobin concentration.However, there was no significant increase in the total white blood cell count.There was also no significant change in all parameters studied with 2-methoxycanthine-6 one. The results suggest that quassia extract possesses antianaemic property. PMID- 22314947 TI - Assessment of chronic administration of Aloe vera gel on haematology, plasma biochemistry, lipid profiles and erythrocyte osmotic resistance in Wistar rats. AB - The study was designed to investigate the effects of chronic administration of Aloe vera gel extract on markers of hepatic damage, lipid profiles and erythrocyte osmotic fragility using the Wistar rats. Forty male Wistar rats divided into four groups of ten rats per group were used in the study. Group I which served as the control received 0.9% physiological saline while those in groups II, III and IV received Aloe vera gel (100, 250 and 500mg/kg), respectively, for four weeks. There was significant increase in the haemoglobin concentration while the PCV, RBC count, MCH and MCHC though showed some marginal increases but the increases were not significant in all the treated rats. No significant change was also observed in the erythrocyte osmotic fragility. However, there were significant reductions in plasma ALT, AST and ALP levels in animals that received the gel compared with the control while the plasma albumin and total protein values were higher than those of the control. All the animals that received the gel also showed significant reduction in plasma total cholesterol, triglycerides and LDL-cholesterol ratio compared with the control. In a similar manner, those animals that were administered with 500mg/kg gel had significantly higher HDL-cholesterol ratio than those of the control. This study showed that, chronic administration of Aloe vera gel extract had no significant effects on the haematological parameters of the rats and did not affect erythrocyte osmotic resistance. It however showed some cholesterol lowering action. PMID- 22314948 TI - Is hypercalcemic diet a possible antidote to oral contraceptive-induced hypertension? AB - Administration of oral contraceptive (OC) has been associated with body fluid retention and in high doses over a long period, promotes hypertension. This present investigation tests the hypothesis that the dietary calcium supplementation increases salt and water excretion in OC (norgestre/ethinylestradiol) treated 32 female albino rats randomly distributed into four (1-4) groups of 8 rats each: Control, OC-treated, OC-treated+ Calcium diet fed and Calcium diet fed only respectively. OC was administered to the appropriate groups by gavage. Experimental diet contained 2.5% calcium supplement. Plasma and urinary [Na+] [K+] were evaluated after 8 weeks of experimentation by flame photometry and plasma [Ca2+] by colorimetric method. OC treatment induced a significant fall in urinary [Na+]. Water excretion was significantly reduced in these animals (control, 3.1+/-0.56 Vs OC-treated rats, 1.47+/-0.16). OC-treated rats had significantly higher plasma [K+] compared to control rats. Calcium supplementation induced increases in plasma [Na+], [K+] and augmented urinary Na+ excretion (OC-treated + Ca2+ diet Vs OC-treated only). Compared with the control rats, high Ca2+ diet fed rats exhibited significant increases in plasma [Na+] and [K+] accompanied by significant decreases in urinary H20 excretion. These results strongly suggest that high dietary Ca2+ supplementation increases salt and water excretion in OC-treated rats and potentially moderates fluid retention and blood pressure in these animals, and may be of clinical significance in OC-induced abnormal fluid retention and perhaps OC-induced hypertension. PMID- 22314949 TI - Effects of aqueous extract of kola nut (Cola Nitida Rubra) on reproductive hormones in rats. AB - Our previous study suggests that aqueous extract of kola nut had effect on reproductive hormones in male rats. This study evaluates the effects of kola nut extract on plasma level of testosterone and luteinizing hormones in male rats. 30 adult male rats were used. These were divided into three groups: group A served as control and it received water only, group B and C received kola nut extract only (8mg/kg body weight), C served as recovery group. All the groups were treated for four weeks. The C which served as recovery group was allowed to recover for another four weeks at the end of the extract administration period. The plasma level of testosterone was significantly increased while that of luteinizing hormone was significantly decreased when compared with control animals. The recovery group showed values that were insignificantly lowered but a bit closer to those of the control animals. This showed that the rats were able to recover to some extent after the extract administration. PMID- 22314950 TI - A comparative study of the plasma level of arginase and rhodanese in smokers and non-smokers. AB - The purpose of this investigation was to determine and compare the activities of arginase and rhodanese in the blood plasma of cigarette smokers and non smokers.The activity of arginase in the blood plasma of smokers was higher than arginase activity in the non-smokers (NS), however,in the smokers with diseases (SWD), the increase was significant. The comparison between the activity of rhodanese in the SWD, smokers without diseases (SWOD) and NS blood plasma revealed a decrease in the activity of rhodanese in NS and no significant difference in the three groups with P=0.8677. This paper reported the enhancing effect of cigarette smoking could have on the disease state of smokers due to high arginase activity. PMID- 22314951 TI - Effects of methionine containing paracetamol formulation on serum vitamins and trace elements in male rats. AB - Methionine is an effective antidote in the treatment of paracetamol-induced toxicity but at large doses it has been reported to induce or aggravate a number of pathological conditions. It also alters plasma levels of many vital elements and molecules. This study was designed to identify if the alteration observed for antioxidant vitamins and minerals especially at sub-toxic and toxic levels of exposure in our earlier study of 24-hour exposure period may warrant trace elements supplementation. This was investigated by carrying out a 48-hour study to test the ability of a living organism to restore homeostasis of these vital molecules and elements. The levels of antioxidant minerals and vitamins were estimated in the serum samples obtained from adult male Wistar rats exposed to paracetamol tablets. At 100 mg?kg BW (body weight) vitamin A, niacin, riboflavin, selenium and manganese were not significantly different from the control group. Moreover at 350 mg?kg, all these indices except zinc were not significantly different in the exposed group compared with controls whereas at 1000 mg?kg level of exposure manganese, selenium and vitamin E were not significantly decreased at the end of 48 hours of exposure but copper, niacin and vitamin A were significantly increased in the exposed group compared with the controls. These results suggest that with time the body may be capable of bringing about restoration of the levels of some of these elements?vitamins. This was more evident at 350 mg?kg level of exposure than a higher dose of 1000 mg?kg level. PMID- 22314952 TI - Epidemiology of clinical isolates of Mycobacterium tuberculosis at Ibadan, Nigeria. AB - Despite the huge burden of tuberculosis (TB) in Nigeria, case detection rate of infectious cases still remain low, thus constituting obstacle to eradication of the disease in the community. We carried out a 15 month (1st January 2008 to 30th March 2009) retrospective review of epidemiology of clinical isolates of M. tuberculosis isolated at TB regional reference laboratory at the department of Medical Microbiology and Parasitology, University College Hospital, Ibadan, Nigeria. Fifty isolates were recovered from 720 specimens during the period of study with a recovery rate of 6.9%. Sixty- two (8.6%) of the specimens were contaminated. Thirty eight (76.0%) isolates were from the specimens of male subjects and 12 (24.0%) from female subjects giving a male to female ratio of 3.2: 1.0 Majority (62.0%) of the isolates were from subjects aged 20 years and above with an isolation rate of 7.3% while only two clinical isolates (4.0%) were recovered from specimens from children. A high yield of 20.8% was recovered from specimen collected from Hausa ethnic group who predominantly domiciled in a particular part of the metropolis. In terms of socio-economic status, clinical isolates recovered from specimens from unskilled workers (76.0%) was more than thrice from that obtained from the professionals (24.0%). Seven (14.0%) of the total isolates were recovered from extra-pulmonary lesions while the majority 43 (86.0%) were for pulmonary TB. The isolation rate from children and extra pulmonary sites are low. This suggests a need to pay more attention to diagnosis of childhood and extra-pulmonary TB in Ibadan, Nigeria. PMID- 22314953 TI - Amelioration of carbon tetrachloride-induced hepatotoxicity and haemotoxicity by aqueous leaf extract of Cnidoscolus aconitifolius in rats. AB - This study was conducted to explore possible protective effect ofCnidoscolus aconitifolius (CA) leaf extract on carbon tetrachloride (CCl4)-induced hepatotoxicity and haemotoxicity in experimental animal models. Thirty six rats of six per group were used in this study. Group I received 10ml/kg normal saline as control. Group II-VI rats were administered with 1.25ml/kg body weight (bwt) of carbon tetrachloride intraperitonealy. Animals in groups III, IV, V and VI were however pre-treated with aqueous extract of Cnidoscolus aconitifolius at 100, 250, 500 and 750mg/kg body weight (bwt) respectively. Administration of CCL4 in untreated rats led to microcytic hypochromic anaemia, thrombocytopenia, increased erythrocyte fragility and stress induced leucocytosis accompanied with significant increase in neutrophils and decrease in lymphocyte counts. CCl4 also led to significant increase in serum transaminases (ALT and AST) and phosphatase (ALP) respectively compared with control animals. Also, CCL4 produced significant increase in serum blood urea nitrogen (BUN) and creatinine compared with normal rats. Pre-treatment with Cnidoscolus aconitifolius leaf extract brought about significant restoration of the haematological parameters to values that were comparable to those of the control with concomitant decrease in the activities of the marker of hepatic damage enzymes (ALT, AST and ALP), in a dose-dependent manner. Similarly, serum levels of blood urea nitrogen (BUN) and creatinine were also brought to near normal by the CA in a dose-dependent manner. From this study, we conclude that pre-exposure to Cnidoscolus aconitifolius leaf extract considerably reduced the effect of CCl4 on the blood parameters and ameliorated hepatic damage by the haloalkane. PMID- 22314954 TI - Effects of aqueous leaf extract of Bryophyllum pinnatum on guinea pig tracheal ring contractility. AB - Aqueous leaf extract of Bryophyllum pinnatum Lam (Crassulaceae) is used as a cough remedy and for the prophylaxis of asthma. Since drugs used for the prophylaxis of asthma may be acting on airway smooth muscles, we investigated the effects of aqueous leaf extract of the plant on the contractile responses of isolated tracheal rings. Guinea pigs were grouped into non-sensitized, ovalbumin (OA)-sensitized, OA-sensitized but 200 mg/kg/day x 21 extract-treated, and OA sensitized but 400 mg/kg/day x 21 extract-treated. The extract was administered orally. Tracheal rings obtained from the four groups were mounted in organ baths and used to test spasmolytic and antispasmodic effects of the extract on histamine or carbachol-induced contractions. Concentrations of 0.125-1.0 mg/ml of the extract did not relax histamine or carbachol-induced precontractions. The presence of 0.25-1.0 mg/ml of the extract in organ baths significantly reduced the maximal contractile responses (Emax) to cumulative concentrations of histamine or carbachol irrespective of the experimental group. pD2 values were significantly reduced for histamine and carbachol in rings obtained from 400 mg/kg/day x 21 extract-treated group. It is concluded that aqueous leaf extract of B. pinnatum possesses antispasmodic effects on the guinea pig tracheal rings. The results lend credence to the use of the extract for the prophylaxis of asthma in ethnomedicine. PMID- 22314955 TI - A study of some rostrofacial indices related to regional anaesthesia of the porcine: implications as an animal model for dental research. AB - There has been a widespread use of pigs in medical and biomedical training and research due to many similarities in the morphophysiology of tissues between swine and humans The aim of this study was to measure some rostrofacial indices of some indigenous pigs in Nigeria, with a view to providing basic information on some clinically important parameters. Using 26 pigs, the mean values for the mandibular lenghts MDL-1 and MDL-2 were 16.74+/-1.76cm and 15.98+/-2.32cm for the males and 18.03+/-3.04 and 17.07+/-2.54 for the females. The mean distance of the infraorbital foramen to the root of the alveolus of premolar three was relatively constant between sexes and age group however, significant differences was found in the distance between the medial mental foramen and the mandibular foramen, between age group within sexes. Several lateral foramina were observed on either side of the bodies of the mandibles, with an average of 6 in the males and 7 in the females with the implications for anaesthesia discussed. With increasing use of the porcine species as experimental models for improvement of human dental implants, this work will further aid the knowledge of the regional anaesthesia of this species in dental implant studies and could be of value in the surgical intervention of priced animals. PMID- 22314956 TI - The effects of health education on knowledge and attitudes to emergency contraception by female students of a tertiary educational institution in Enugu, South East Nigeria. AB - This was an intervention study to assess the effects of health education on the knowledge and attitudes to emergency contraception (EC) by female students of University of Nigeria in southeast Nigeria. A structured questionnaire was used to collect data from 337 female students of a tertiary educational institution (150 in the study group and 187 from the control group) who were selected by multistage sampling. Subsequently, health education was conducted only among students in the study institution. Three months after this intervention, its effects were assessed through a survey using the same structured questionnaire employed in the baseline survey. Unlike the pre-intervention results, knowledge of EC was significantly higher among the study group than the controls. Attitudes to EC were also more favourable at the post- intervention survey among the study group. Health education can effectively improve knowledge and attitudes to EC among female students of tertiary institutions and this should be encouraged. PMID- 22314957 TI - Thyroid dysfunction in type 2 diabetics seen at the University College Hospital, Ibadan, Nigeria. AB - Thyroid dysfunction complicates the metabolic derangement observed in Diabetes Mellitus (DM). It is necessary to recognize and treat it when present in order to achieve stability of metabolic control in these patients. The prevalence of thyroid dysfunction in type-2 diabetics in our environment is not known. This study was therefore designed to determine the prevalence of thyroid dysfunction in Type 2 diabetics seen at the Metabolic Research Unit of University College Hospital, Ibadan, Nigeria. Serum TSH, Free T3 and Free T4 assays were performed using Automated Enzyme Immunoassay platform on fresh sera from volunteers comprising 64 adult type 2 diabetics and 36, age matched, non diabetic controls; weight, height and blood pressures were measured in all subjects. In addition, past lipid profile results of type 2 diabetics were retrieved from medical records. Thyroid dysfunction was present in 19 (29.7%) of 64 type 2 diabetics and 1 (2.8%) of 36 non diabetic controls.The prevalence of thyroid dysfunction is 32.4% in females and 25.9% in males. Secondary hypothyroidism was seen in 78.9%, sub-clinical hypothyroidism in 15.8%, and sub-clinical hyperthyroidism 5.2% of subjects with thyroid dysfunction. Abnormal lipid profiles were seen in 35.4% of euthyroid type 2 diabetics and 100% of hypothyroid type 2 diabetics. 87.5% of type 2 diabetics and 38.8% of controls were hypertensive. 7.8% of type 2 diabetics and 50% of controls were obese. The prevalence of thyroid dysfunction in type 2 is higher in type 2 diabetics than in controls. More of Type 2 diabetics were obese and more of them were hypertensive compared to controls. The approach of using TSH first in screening for thyroid dysfunction is not sufficient in type 2 diabetics. Routine screening for thyroid dysfunction should be carried out in type 2 diabetics. PMID- 22314958 TI - Effect of aqueous fruit extract of Xylopia aethiopica on intestinal fluid and glucose transfer in rats. AB - Intestinal fluid and glucose absorption was studied in jejunal and ileal segments in Xylopia aethiopica fed rats using inverted sac technique. Thirty male Wistar rats were assigned into three groups of 10 rats each; control, 100mg/kg and 200mg/kg Xylopia aethiopica treated groups. The control group received normal rat chow and water while the low dose and high dose groups received oral administration of Xylopia aethiopica extract at doses of 100mg/kg and 200mg/kg body weight respectively in addition to daily rat chow and water intake for 28 days. The results showed significant reduction and increase in fluid transfer in the jejunum and ileum respectively compared with control. 100mg/kg increased gut fluid uptake in the ileum while 200mg/kg treatment reduced uptake in jejunum compared with control. Both doses had significantly increased jejunal and ileal glucose transfer. Gut glucose uptake was increased in jejunum and ileum of Xylopia aethiopica treated groups. Both doses increased the crypt depth but significantly decreased the villus height in the ileum. In conclusion, increased ileal gut fluid uptake may be beneficial in diarrheal state while an enhanced glucose uptake implies that glucose substrate may be made available to cells for synthesize of ATP for cellular activities. PMID- 22314959 TI - Waist circumference, waist to hip ratio, and body mass index in the diagnosis of metabolic syndrome in Nigerian subjects. AB - Metabolic syndrome is the commonest controllable precursor of cardiovascular and end stage renal diseases. While central obesity is recognized universally as its strongest component, there is the need for an accurate and affordable tool to screen for the presence of metabolic syndrome in every community. The easiest and cheapest measures of obesity are the body mass index (BMI), waist circumference (WC) and waist to hip ratio (WHR). This study investigated the potential of BMI, WHR and WC in diagnosis of metabolic syndrome (MS) in Nigerian subjects.This cross sectional study involved three hundred and thirty eight apparently healthy adult Nigerians recruited within the University College Hospital and its environs were evaluated for the features of metabolic syndrome using the World Health Organisation and the NCEP ATP 111 criteria. BMI, WC, WHR, Blood Pressure, Fasting Lipid Profile and Fasting Plasma Glucose were measured in each participant. Correlation between BMI, WC, WHR and Blood Pressure, Fasting Lipid Profile and Fasting Plasma Glucose which are other components of MS was determined and empirical Receiver Operating Characteristics (ROC) analysis was used to evaluate each of them as predictors of MS. The prevalence of MS in the studied population was significantly higher (36.7%) using NCEP definition than (23.7%) using WHO definition. By both definitions, this prevalence was higher in females than in males. WC was positively correlated with FPG and TG (r=0.560 and 0.436 respectively; P=0.000) in the NCEP category while WC was positively correlated with FPG, SBP and DBP (r=0.254, 0.480, and 0.490 respectively; P>0.05) in the WHO category. ROC Analysis shows WC having the highest AUC (0.785) hence diagnoses MS more accurately than both BMI (0.733) and WHR (0.783) using in the NCEP ATP 111 criteria. The highest Area Under Curve (AUC) was observed in WHR (0.837) followed by WC (0.799) in the WHO category. Both WC and WHR are shown to be good predictors of the presence of MS. It will be appropriate to incorporate WC measurement into routine general physical examination in our clinics. PMID- 22314960 TI - Proceeding of the 30th annual scientific conference of the Physiological Society of Nigeria held at the Department of Physiology, College of Medicine, Lagos State University, Ikeja, Lagos. PMID- 22314961 TI - T2* measurement of the knee articular cartilage in osteoarthritis at 3T. AB - PURPOSE: To measure reproducibility, longitudinal and cross-sectional differences in T2* maps at 3 Tesla (T) in the articular cartilage of the knee in subjects with osteoarthritis (OA) and healthy matched controls. MATERIALS AND METHODS: MRI data and standing radiographs were acquired from 33 subjects with OA and 21 healthy controls matched for age and gender. Reproducibility was determined by two sessions in the same day, while longitudinal and cross-sectional group differences used visits at baseline, 3 and 6 months. Each visit contained symptomological assessments and an MRI session consisting of high resolution three-dimensional double-echo-steady-state (DESS) and co-registered T2* maps of the most diseased knee. A blinded reader delineated the articular cartilage on the DESS images and median T2* values were reported. RESULTS: T2* values showed an intra-visit reproducibility of 2.0% over the whole cartilage. No longitudinal effects were measured in either group over 6 months. T2* maps revealed a 5.8% longer T2* in the medial tibial cartilage and 7.6% and 6.5% shorter T2* in the patellar and lateral tibial cartilage, respectively, in OA subjects versus controls (P < 0.02). CONCLUSION: T2* mapping is a repeatable process that showed differences between the OA subject and control groups. PMID- 22314962 TI - Enantioselective trapping of an alpha-chiral carbanion of acyclic nitrile by a carbon electrophile. AB - An alpha-chiral nitrile carbanion generated by deprotonation of enantioenriched O carbamoyl cyanohydrin was trapped in situ with ethyl cyanoformate to give the corresponding ester derivative in 92% yield and 90 : 10 er, providing the first example of trapping of an alpha-chiral acyclic nitrile carbanion that has been considered to be very configurationally labile. PMID- 22314963 TI - Knee wear measured in retrievals: a polished tray reduces insert wear. AB - BACKGROUND: Polyethylene wear is often cited as the cause of failure of TKA. Rotating platform (RP) knees show notable surface damage on the rotating surface raising concerns about increased wear compared to fixed bearing inserts. QUESTIONS/PURPOSES: We therefore addressed the following questions: Is wear in RP inserts increased compared to that in fixed bearing inserts? Does the surface roughness of the tibial tray have a measurable impact on in vivo wear of modular knees? And does wear rate differ between posterior stabilized (PS) and cruciate retaining (CR) knees? METHODS: We compared wear in two series of retrieved knee devices: 94 RP mobile bearings with polished cobalt-chrome (CoCr) trays and 218 fixed bearings with both rough titanium (Ti) and polished CoCr trays. Minimum implantation time was 0.4 months (median, 36 months; range, 0.4-124 months) and 2 months (median, 72 months; range, 2-179 months) for the RP and fixed bearing series, respectively. RESULTS: Wear rate was lower for RP inserts than for fixed bearing inserts. Backside wear rate was lower for fixed bearing inserts mated to polished CoCr trays than for inserts from rough Ti trays. Inserts against polished trays (RP or fixed bearing) showed no increase in wear rate increase over time. Wear rate of PS knees was similar to that of CR knees. CONCLUSIONS: We found mobile bearing knees have reduced wear rate compared to fixed bearings, likely due to the polished CoCr tibial tray surface. Fixed bearing inserts in polished CoCr trays wear less than their counterparts in rough Ti trays, and the wear rate of inserts from polished CoCr trays does not appear to increase with time. PMID- 22314964 TI - A split ligand for lanthanide binding: facile evaluation of dimerizing proteins. AB - Luminescence of lanthanides is attractive for biological applications due to its long lifetime and sharp emission profiles. We describe the split display of a lanthanide binding ligand that allows facile evaluation of dimerizing proteins. The split lanthanide ligand is cysteine reactive, and therefore should be readily applicable to a variety of protein systems. PMID- 22314965 TI - Cohort profile: the European Male Ageing Study. AB - The European Male Ageing Study (EMAS) was designed to examine the hypothesis that inter-individual and regional variability in symptomatic dysfunctions, alterations in body composition and health outcomes in ageing men can be explained by different rates of decline in anabolic hormones, the most important of which being testosterone. Between 2003 and 2005, 3369 community-dwelling men, aged between 40 and 79 years, were recruited from population-based registers in eight European centres to participate in the baseline survey, with follow-up investigations performed a median of 4.3 years later. Largely, identical questionnaire instruments and clinical investigations were used in both phases to capture contemporaneous data on general health (including cardiovascular diseases and chronic conditions), physical and cognitive functioning, mental health, sexual function, quality of life, bone health, chronic pain, disease biomarkers, hormones (sex hormones and metabolic hormones) and genetic polymorphisms. EMAS actively encourages new collaborations, data sharing for validation studies and participation in genetic study consortia. Potential collaborators should contact the principal investigator (F.C.W.W.) in the first instance. PMID- 22314966 TI - Gestational weight gain and child cognitive development. AB - BACKGROUND: The Institute of Medicine (IOM) recently revised gestational weight gain (GWG) guidelines, yet little is known about the association between extremes of GWG and child cognition. METHODS: The authors examined this association using U.S. Collaborative Perinatal Project data (1959-73). Women with a calculable GWG and term, singleton children were eligible for inclusion. Children (31 968 individuals, including 8704 siblings) were assessed at 4 (Stanford-Binet Intelligence Scale, Graham-Ernhart Block Sort Test) and 7 years of age [Wechsler Intelligence Scales for Children, Wide Range Achievement Test (WRAT)]. Multiple regression with restricted cubic splines and generalized estimating equations (GEEs) was used. Fixed-effects (FE) models were also applied to control for confounders shared within sibships. RESULTS: GWG displayed non-linear inverted U shaped associations with most outcomes when the data were analysed using GEE, suggesting a detrimental influence of low and high GWG on cognition. After controlling for familial factors (FE), all associations were null except for a positive linear association between GWG above the IOM-recommended ranges and WRAT spelling (beta = 1.41, 95% confidence interval: 0.13, 2.70). CONCLUSIONS: Familial factors are important confounders of the association between GWG and cognitive development at 4 and 7 years of age. After controlling for such factors, GWG was generally unassociated with child development. PMID- 22314967 TI - Analysis of crucial factors resulting in microarray hybridization failure. AB - The factors that affect the formation and stability of DNA/DNA duplexes are complicated and still mostly unknown. In this study attempts were made to look for the crucial factor affecting hybridization failure in DNA microarray assays. A comprehensive range of factors were investigated simultaneously using a 25-mer oligonucleotide Potyvirus microarray. These included steric hindrance, direct/indirect labelling types, distance of a probe to the fluorescent labelling end, target (the DNA fragment used to hybridize with microarray probes) strand types either single strand or double strand, probes without mismatch and with different numbers of mismatch nucleotides (up to 36%) and different mismatch locations (5' end, centre and 3' end), probe GC content and T(m), secondary structures of probes and targets, different target lengths (0.277 kb to ~1.3 kb) and concentrations (0.1-30 nM). The results showed that whilst most of these known factors were unlikely to be the main causes of failed hybridization, there was strong evidence suggesting that the viral amplicon target structure is the most crucial factor. However, computing predicted target secondary structures by Mfold showed no correlation with the hybridization results. One explanation is that the predicted target secondary structures are different from the real structures. Here we postulate that the real target structure might be a combination of secondary structures resulting in a three-dimensional structure from exposure to three types of sub-structures: (1) a completely exposed linear structure to allow probes access for the successful hybridization and showing strong fluorescent signals; (2) a partially exposed structure to allow unstable binding and showing weak fluorescent signals; (3) a closed structure resulting in failed hybridization. These results are very important for microarray based studies as they not only provide an explanation for some current controversial results, but also provide potential resolution for the future studies. Due to the lack of available software for predicting the true target structure, development of microarrays should conduct an initial oligonucleotide probe selection procedure and those probes with capacity to hybridize with the target should be considered for the microarray development. PMID- 22314968 TI - The inhibition by di(2-ethylhexyl)-phthalate of erg-mediated K+ current in pituitary tumor (GH3) cells. AB - DEHP (bis(2-ethylhexyl)-phthalate) known to be an endocrine-disrupting chemical is a widely used phthalate. Little information regarding the effects of phthalate esters on ion currents is available. In this study, the effects of DEHP and other phthalate esters (DBEP: di(2-butoxyethyl)-phthalate and DMGP: di(2-methylglycol) phthalate) on ion currents were investigated in pituitary GH3 cells. Hyperpolarization-elicited K+ currents in GH3 cells bathed in high-K+, Ca2+-free solution were examined to evaluate the effects of DEHP, DBEP, and DMGP on the ether-a'-go-go-related-gene (erg) K+ current (IK(erg)). Addition of DEHP to GH3 cells suppressed the amplitude of IK(erg) in a concentration-dependent manner with an IC50 value of 16.3 MUM. With a two-pulse protocol, addition of DEHP shifted the activation curve of IK(erg) to a depolarized potential by approximately 10 mV with no change in the rate of IK(erg) deactivation. This compound did not have any effects on delayed rectifier K+ current in GH3 cells, while 4-aminopyridine-3-methanol (100 MUM) suppressed this current significantly. DBEP (30 MUM) had little or no effect on IK(erg), while DMGP (30 MUM) slightly reduced it. In inside-out configuration, DEHP (30 MUM) applied to the bath slightly reduced the activity of large-conductance Ca2+-activated K+ channels. DEHP (30 MUM) increased the frequency of spontaneous action potentials (APs); however, this compound at the same concentration had no effect on AP firing in KCNH2 siRNA-transfected GH3 cells. The effects described herein can contribute to their actions on functional activity of endocrine or neuroendocrine cells if similar results are found in vivo. PMID- 22314970 TI - Pathways to Earth-like atmospheres. Extreme ultraviolet (EUV)-powered escape of hydrogen-rich protoatmospheres. AB - We discuss the evolution of the atmosphere of early Earth and of terrestrial exoplanets which may be capable of sustaining liquid water oceans and continents where life may originate. The formation age of a terrestrial planet, its mass and size, as well as the lifetime in the EUV-saturated early phase of its host star play a significant role in its atmosphere evolution. We show that planets even in orbits within the habitable zone of their host stars might not lose nebular- or catastrophically outgassed initial protoatmospheres completely and could end up as water worlds with CO2 and hydrogen- or oxygen-rich upper atmospheres. If an atmosphere of a terrestrial planet evolves to an N2-rich atmosphere too early in its lifetime, the atmosphere may be lost. We show that the initial conditions set up by the formation of a terrestrial planet and by the evolution of the host star's EUV and plasma environment are very important factors owing to which a planet may evolve to a habitable world. Finally we present a method for studying the discussed atmosphere evolution hypotheses by future UV transit observations of terrestrial exoplanets. PMID- 22314971 TI - Analysis of ECOG performance status in head and neck squamous cell carcinoma patients: association with sociodemographical and clinical factors, and overall survival. AB - PURPOSE: In the present study, we analyzed sociodemographical and clinical factors, and the Eastern Cooperative Oncology Group performance status (ECOG-PS) scale in head and neck squamous cell carcinoma (HNSCC) patients. We evaluated the impact of a range of variables on overall survival. METHODS: We investigated a sample of HNSCC patients (n = 671), using sociodemographical and clinical information, and survival data collected from a review of epidemiological, clinical, and treatment reports. Statistical associations were analyzed by bivariate and multivariate statistical tests. Statistical significance was set at p < 0.05. RESULTS: Of patients 85.4% recorded good ECOG-PS scores. Poor ECOG-PS scores were associated with the covariates indicative of dysphagia [odd ratios (OR) = 2.660, CI 95% = 1.661-4.260, p = 0.000] and large-size malignant disease (T3-T4; OR = 5.337, CI 95% = 2.251-12.652, p = 0.000). Overall survival analysis revealed that ECOG-PS scores (OR = 1.879, CI 95% = 1.162-3.038, p = 0.010), tumor size (OR = 1.665, CI 95% = 1.035-2.680, p = 0.036), and the presence of cervical metastasis (OR = 3.145, CI 95% = 2.008-4.926, p = 0.000) were independent predictors. CONCLUSION: Evaluation of physical consumption in head and neck cancer patients at diagnosis may indicate a more aggressive type of malignant disease. Thus, the ECOG-PS scale may help to identify HNSCC patients in need of rapid referral, who may benefit from specific therapeutic and rehabilitative interventions. PMID- 22314972 TI - The nutritional risk in oncology: a study of 1,453 cancer outpatients. AB - PURPOSE: There is little information about the nutritional status of cancer outpatients because the practice of nutritional screening is rarely performed. This study aims to define the pattern of scores of nutritional risk in 1,453 outpatients and factors associated with a high nutrition risk score, to facilitate the identification of such patients by the oncologists. METHODS: We prospectively screened the nutritional status of cancer outpatients according to the NRS-2002 score which combines indicators of malnutrition and of severity of the disease (1-3 points, respectively). A score >= 3 indicates "nutritional risk". The association of the nutritional scores with some patient/tumour/therapy related variables was investigated through univariable and multivariable linear regression models. RESULTS: Thirty-two percent of outpatients were at nutritional risk. Primary tumour site, Eastern Cooperative Oncology Group score and presence of anorexia or fatigue were significantly associated with the nutrition risk score. Depending on the combination of these variables, it was possible to estimate different probabilities of nutritional risk. CONCLUSIONS: The frequency of a relevant nutritional risk was higher than expected considering the favourably selected population. The nutritional risk was associated with common clinical variables which are usually recorded in the charts and could easily alert the oncologist on the need of a further nutritional assessment or a nutritional support. PMID- 22314973 TI - Advance directives: prevalence and attitudes of cancer patients receiving radiotherapy. AB - PURPOSE: Advance directives (AD) are becoming increasingly widespread. We examine the prevalence of AD and the factors associated with AD in tumor patients during radiotherapy. METHODS: A standardized questionnaire was handed out to all tumor patients on 9 random days with an interval of at least 12 weeks. The data were analyzed in a bivariate and multivariate way. RESULTS: Of 1,208 questionnaires, 658 were completed and returned (54.5%). Of respondents, 23.6% had already signed an AD, 53.3% thought they were likely to sign an AD, 9.0% did not want to sign an AD, and 4.9% were not familiar with advance directives. Patients who have signed an AD and those who are likely to sign one think that ADs facilitate the physician's decision-making process (97.7% cf. 94.5%) and that they ease the burden on relatives (98.5% cf. 98.8%). Regardless of an AD having been signed, every second respondent was of the opinion that AD facilitates consultations rather than serving as a directive (55.1% cf. 57.3%). Patients likely to sign an AD are significantly younger compared to those unlikely to do so and have suffered from their tumor disease for a shorter period of time. CONCLUSIONS: Of advance directives is widely accepted among the tumor patients surveyed. Advanced directives are not exclusively seen as instruments for surrogate decision making, but also as mediums to improve communication. Training of physicians and additional offers for patients could increase the actual number of ADs and perhaps improve physicians and relatives understanding of patients needs and wishes. PMID- 22314974 TI - Worklife Improvement and Leadership Development study: a learning experience in leadership development and "planned" organizational change. AB - BACKGROUND: In response to increasing recognition of the importance of quality health care work environments, the Alberta Cancer Board initiated a province-wide leadership development program to plan for organizational change through a series of stages. In 2004, the Leadership Development Initiative (LDI) was implemented to facilitate organizational learning using a cohort-based leadership intervention based on a communities of practice framework. PURPOSES: The aim of the Worklife Improvement and Leadership Development study was to examine both the outcomes and experiences of participants of the LDI program to better understand leadership development, implementation, and its impact on worklife quality among 5 cohorts of health care managers and staff at the Alberta Cancer Board. METHODOLOGY/APPROACH: This study used both structured survey and interview methods, using a pretest-intervention-posttest quasi-experiment without a control group design, to assess the effects of LDI on worklife of leaders and staff. Surveys included the Leadership Practices Inventory and Areas of Worklife Scale, which looked at meaningfulness of work and organizational engagement. Interviews and focus group data provided a more detailed description of the experience of leadership development and perceptions of organizational worklife. FINDINGS: The study revealed layers of information about the complexity of individual and collective leadership in a cohort-based design, perceptions of leadership initiatives, organizational worklife, and planned organizational change. Our findings suggest that early changes in how leaders reflected on their own skills and practices (Leading Self) were positive; however, growing disengagement as the LDI continued was evident in the focus group data, particularly when change in behavior of others was not perceived to be evident. PRACTICE IMPLICATIONS: To support the effectiveness and success of a leadership initiative, managers and administrators need to implement strategies designed to help leaders grow and cope with ongoing flux of organizational change and stagnation. PMID- 22314975 TI - Optimal solution for a cancer radiotherapy problem. AB - We address the problem of finding the optimal radiotherapy fractionation scheme, representing the response to radiation of tumour and normal tissues by the LQ model including exponential repopulation and sublethal damage due to incomplete repair. We formulate the nonlinear programming problem of maximizing the overall tumour damage, while keeping the damages to the late and early responding normal tissues within a given admissible level. The optimum is searched over a single week of treatment and its possible structures are identified. In the two simpler but important cases of absence of the incomplete repair term or of prevalent late constraint, we prove the uniqueness of the optimal solution and we characterize it in terms of model parameters. The optimal solution is found to be not necessarily uniform over the week. The theoretical results are confirmed by numerical tests and comparisons with literature fractionation schemes are presented. PMID- 22314976 TI - Highly effective binding of neutral dinitriles by simple pillar[5]arenes. AB - Highly effective binding of neutral dinitriles by simple alkyl-substituted pillar[5]arenes and the formation of interpenetrated geometries are reported. The resulting host-guest complexes represent one of the most efficient recognition motifs based on pillararenes. PMID- 22314977 TI - The importance of slow motions for protein functional loops. AB - Loops in proteins that connect secondary structures such as alpha-helix and beta sheet, are often on the surface and may play a critical role in some functions of a protein. The mobility of loops is central for the motional freedom and flexibility requirements of active-site loops and may play a critical role for some functions. The structures and behaviors of loops have not been studied much in the context of the whole structure and its overall motions, especially how these might be coupled. Here we investigate loop motions by using coarse-grained structures (C(alpha) atoms only) to solve the motions of the system by applying Lagrange equations with elastic network models to learn about which loops move in an independent fashion and which move in coordination with domain motions, faster and slower, respectively. The normal modes of the system are calculated using eigen-decomposition of the stiffness matrix. The contribution of individual modes and groups of modes is investigated for their effects on all residues in each loop by using Fourier analyses. Our results indicate overall that the motions of functional sets of loops behave in similar ways as the whole structure. But overall only a relatively few loops move in coordination with the dominant slow modes of motion, and these are often closely related to function. PMID- 22314978 TI - Protein kinase G may exert pro-degradation inhibition on nitric oxide synthase. AB - Nitric oxide synthase (NOS) is regulated by protein-protein interactions. We had earlier shown that PKG inhibits activated NOS in endothelial cells and speculated that PKG phosphorylation of NOS terminates its activity. The present work examines if PKG activation increases breakdown of NOS. Diamino-fluorescein fluorescence spectrometry of real time NO production was used to establish that isolated ovine lung microvascular endothelial cells responded to PKG modulation as previously reported. Fluorescence activated cell sorter (FACS) analysis was used to establish that 8-Br-cGMP, a PKG activator, caused carboxy terminal deletion on NOS, a sign of degradation. Western blot analysis was used to investigate NOS fragments in control and 5 min 8-Br-cGMP treated cells. PKG activator 8-Br-cGMP, at 20 nM, 200 nM, and 2 MUM, decreased nitric oxide production in a dose dependent manner (p<0.05 in all cases). PKG inhibitors: 100 MUM Rp-8-Br-PET-cGMPS, 50 nM Rp-8-pCPT-cGMPS, or 4 MUM Rp-8-Br-cGMPS Na significantly increased NO production (p<0.05) showing that PKG normally inhibits basal NO production. 8-Br-cGMP (100 nM) abrogated the elevation in NO production produced by the PKG inhibitors. FACS analysis revealed that PKG decreased NOS carboxy terminal labeling. Western blot analysis revealed that 8-Br-cGMP increased N-terminal serine-116 phosphorylated NOS fragments of molecular weights of about 60, 50 and 35 kDa. PKG may be a post-activation inhibitor of NOS, possibly important for the degradation of the spent enzyme. PMID- 22314979 TI - Prevalence of left ventricular hypertrophy in hypertensive and normotensive type 2 diabetic females in Port Harcourt. AB - This study investigated the prevalence of electrocardiographically determined left ventricular hypertrophy in hypertensive and normotensive type 2 diabetic females who went for consultation at the University of Port Harcourt Teaching Hospital (UPTH), Rivers State, Nigeria. Two hundred participants mean age 52 years, attending the medical outpatient clinic over a 6-month period were recruited for the study. Of the population studied, 16.5% of the hypertensive and 13.0% of the normotensive diabetics had left ventricular hypertrophy. Cardiovascular abnormalities notably bifascicular block, left atrial block, right ventricular enlargement, and right atrial enlargement were predominately among hypertensive diabetes and also notably was arrhythmia and atrial flutter among normotensive diabetes. The significance of these findings is discussed. PMID- 22314980 TI - Water ingestion affects orthostatic challenge-induced blood pressure and heart rate responses in young healthy subjects: gender implications. AB - Evidence exists that women have lower orthostatic tolerance than men during quiescent standing. Water ingestion has been demonstrated to improve orthostatic tolerance in patients with severe autonomic dysfunction. We therefore sought to test the hypothesis that water ingestion would improve orthostatic tolerance in healthy young women more than in aged-matched men. Thirty seven (22 men and 15 women) healthy subjects aged 22.5+/- 1.7 and 21.5+/-1.4 (means+/-SD) respectively, ingested 50ml (control) and 500ml of water 40min before orthostatic challenge on two separate days of appointment in a randomized controlled, cross over design. Seated and standing blood pressure and heart rate were determined. Orthostatic tolerance was assessed as the time to presyncope during standing. Ingesting 500ml of water significantly improves orthostatic tolerance by 22% (32.0 +/- 5.2 vs 26.2 +/- 2.4min; p< 0.05) in men and by 33% (24.2+/-2.8 vs 18.3 +/- 3.2; p< 0.05) in women. Thirty minutes after ingesting 500ml of water, seated systolic blood pressure, diastolic blood pressure, pulse pressure and mean arterial pressure rose significantly in men while only systolic blood pressure and pulse pressure rose significantly in women. However ingesting 500ml of water did not have significant effect on seated heart rate in both men and women. Ingestion of 500ml of water significantly attenuated both the orthostatic challenge-induced increased heart rate and decreased pulse pressure responses especially in women. Diastolic blood pressure tended to be positively correlated with orthostatic tolerance strongly in men than in women. Pulse pressure correlated positively while heart rate correlated negatively to orthostatic tolerance in women but not in men independent of other correlates. Water ingestion is associated with orthostatic tolerance strongly in women but weakly in men independent of other correlates. In conclusion, the findings in the present study demonstrated that water ingestion caused improvement strongly in young women than in young men. This improvement is associated with increased pulse pressure and decreased tachycardiac responses during orthostatic challenge. PMID- 22314981 TI - Erythrocytic parameters as indicators for differentiating between the pregnant and pseudopregnant bitches in Nigeria. AB - The erythrocytic parameters during pregnancy and pseudopregnancy in bitches were studied and compared in 8 bitches aged 2 -3 years and weighing 10-12 kg. Blood samples were collected from the bitches before mating, during the three trimesters of pregnancy and the post partum period. The packed cell volume (PCV %), haemoglobin concentration (Hb gm/dl), red blood cell count(x10(6)/ul) were determined using standard methods. The mean corpuscular volume (MCV) and mean corpuscular haemoglobin concentration (MCHC) were then calculated. Six of the bitches were pregnant and 2 were pseudopregnant. The results showed that in pregnant bitches, the PCV decreased significantly from the premating values of 51.37+0.94% to 34.00+8.04% during the third trimester of pregnancy (P<0.05). There was also a significant decrease in Hb values (P<0.05) from the premating period (16.30 +/- 0.20gm/dl) to the third trimester of pregnancy (11.25+/ 1.80gm/dl). The values of Red blood cells (RBCx10(6)/MUl) during the premating period (12.70+3.15) were not significantly different from the values during the first second and third trimesters (11.13+3.87, 10.38+4.54 and 12.24+3.15, respectively). The trend of decrease in PCV and Hb values were not observed in the bitches with pseudopregnancy. This shows that these erythrocytic parameters can be used to detect and differentiate between pregnancy and pseudopregnancy in bitches as early as the first 20 days post mating. PMID- 22314982 TI - Anogenital distance and umbilical cord testosterone level in newborns in Zaria, Northern Nigeria. AB - The anogenital distance (AGD) is the distance between the anus and the base of the penis in males and anus to fourchette (AF) distance in females and is a sexually dimorphic index that, on average, is twice as great in males as in females, so it is used as an indicator of appropiate masculine development. In this study, the anogenital distance (AGD) and anthropometric measurements such as birth weight, birth length, head circumference and placenta weight of 200 newborns (100 male, 100 female) were taken and umbilical cord serum was assayed for testosterone concentration using Radioimmunoassay (Microwell). Data obtained were analysed using Student t-test and Pearson's Correlation Analysis as applicable. Results revealed that mean total anogenital distance was 22.53+/ 0.70mm, and it was significantly higher in males: 31.11+/-0.64mm than in females: 13.89+/-0.26mm and we observed that there was positive correlation between birth weight and AGD in females. In males head circumference correlated positively with AGD. The mean cord testosterone concentration was 2.78+/-0.30ng/ml in males and 2.09+/-0.22ng/ml in females and did not have any significant correlation with anogenital distance. It was concluded that AGD of the population studied, though high was not significantly higher than AGD in other parts of the world and umbilical cord testosterone level did not have any significant effect on AGD. PMID- 22314983 TI - The relationship between body mass index, semen and sex hormones in adult male. AB - This study was aimed at evaluating the relationship between body mass index, sex hormones and semen characteristics in male adults. 120 male adults aged 20 to 50 years who consented to participate in the study were used. Serum samples collected from each subject were analyzed for luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), progesterone, estradiol and testosterone by classical ELISA method. Semen samples obtained by masturbation after 72 hours of abstinence were analyzed for sperm count and motility. The results showed statistically significant correlations at 99% confidence level between body mass index and serum concentrations of progesterone and oestradiol and sperm count. No significant correlations were observed between body mass index and sperm motility, serum concentrations of prolactin, testosterone and luteinizing hormone. In conclusion, this study has shown that statistically significant correlations exist between body mass index, semen characteristics and male sex hormones and may broaden our understanding of the physiology of male fertility/infertility. PMID- 22314984 TI - Sub-clinical hypothyroidism in infertile Nigerian women with hyperprolactinaemia. AB - Studies on the impact of subclinical hypothyroidism in infertility are scarce and this seeks to determine the proportion of infertile Nigerian women with hyperprolactinaemia that had subclinical hypothyroidism. Serum prolactin and thyroid stimulating hormone were determined using ELECSYS 1010 auto analyzer. Two hundred infertile women were evaluated and 67(33.7%) had hyperprolactinaemia. Subclinical hypothyroidism was observed in 14.9% of women with hyperprolactinaemia, 4.5% and 10.5% of women with primary and secondary infertility, while hyperprolactinaemia was observed in 29.9% and 70.1% in primary and secondary infertility respectively. Mean levels of thyroid stimulating hormone and prolactin were higher in secondary infertility than primary infertility. Subclinical hypothyroidism and hyperprolactinaemia were higher in secondary infertility than primary infertility. The ratio of proportions between hypothyroidism and hyperprolactinaemia was 1:7. PMID- 22314985 TI - Gastric cytoprotection and honey intake in albino rats. AB - Beneficial effect of honey has been widely reported particularly on wound healings, gastrointestinal disorders and as antibacterial agent. However, there is paucity of report on its cytoprotective effect on the gastric mucosa despite its common usage worldwide including Nigeria. This study was therefore carried out to evaluate the effect of this widely consumed substance on gastric mucosa using animal model and also to explore possible mechanism of its action on the gastric mucosa .Twenty male adult albino rats of Wistar strain, weighing between 210-220g were used in the experiment. They were randomly assigned into two groups, the control group and the honey-fed (test) group, each containing ten rats. The Control group was fed on normal rat feed and water while the test group was fed on normal rat feed with honey added to its drinking water (1ml of honey for every initial 10ml of water for each rat daily) for twenty two weeks. After twenty two weeks the rats were weighed after being starved overnight. They were anaesthetized with urethane (0.6ml/100g body weight). Gastric ulceration was induced using 1.5ml acid-alcohol prepared from equivolume of 0.1NHCl and 70% methanol introduced into the stomach via a portex cannula tied and left in place following an incision made on the antral-pyloric junction of the stomach. The acid-alcohol was allowed to stay for 1hr. After 1hr, laparatomy was performed and the stomach isolated, cut open along the greater curvature, rinsed with normal saline and fastened in place with pins on a dissecting board for ulcer examination and scores. The result obtained showed mean ulcer scores of 14.5+/ 0.70 for the control group and 1.6+/-0.11 for the test group. The result showed that honey significantly reduced ulcer scores as well as caused scanty haemorrhage in the test group compared with increased ulcer scores and multiple haemorrhage in the control group. It is therefore concluded that honey intake offered cytoprotection on the gastric mucosa of albino rats. PMID- 22314986 TI - Gastro-protective effect of methanol extract of Ficus asperifolia bark on indomethacin-induced gastric ulcer in rats. AB - The gastro-protective and antioxidant effects of methanol extract of Ficus asperifolia bark on indomethacin induced gastric ulcer were investigated in male rats. Thirty two male rats divided into 4 equal groups and were treated as follows: group1 (control), 0.5ml of 5% tween 80 (vehicle for the extract), groups 2 and 3, 100 and 500mg/kg of Ficus asperifolia extract respectively and group 4, cimetidine (100mg/kg). After two weeks of daily oral administration of vehicle, extract or cimetidine, gastric ulcer was induced in all rats with indomethacin (40 mg/kg, p.o). Gastric juice pH, gastric acid concentration, gastric ulcer score, percentage gastric ulcer inhibition, activity levels of superoxide dismutase (SOD), catalase and malondiadehyde (MDA) were determined. Ficus asperifolia extract significantly increased gastric pH (p<0.05) but decreased (p<0.01) gastric acid secretion in dose dependent manner when compared with the control. Inhibition of gastric ulcer in extract and cimetidine treated rats was similar. Activities of SOD and catalase were significantly increased (p<0.05) while MDA was significantly decreased (p< 0.05) in extract treated rats when compared with the control. The results suggest that Ficus asperifolia possesses gastro-protective and antioxidant properties against gastric ulcer induced by indomethacin. PMID- 22314987 TI - Gastro-protective effect of crude hexane leaf extract of Sesamum indicum in rabbits. AB - The gastroprotective effect of the hexane extract of the leaves of Sesamum indicum (HESI) was investigated in twenty-eight male rabbits. Gastroprotective activity against necrotizing agent induced ulceration was studied. Gastric wall mucus was determined by standard methods. Anti-secretory activity was determined in twelve pyloric-ligated rabbits. Phytochemical and acute toxicity tests were performed. Results showed that the hexane extract of S. indicum significantly reduced gastric ulcers induced by necrotizing agent when compared with values obtained with the negative control (p<0.01). Pre-treatment with graded doses of HESI significantly increased gastric mucous in a dose dependent manner when compared with negative control (p<0.001). Misoprostol significantly protected rabbits from necrotizing agent induced ulceration by 99.9% when compared with negative control (p<0.01). Misoprostol also significantly increased mucous turnover with mean gastric mucous of 597.75 +/- 4.70MUg Alcian blue/g wet tissue when compared with the negative control (p<0.001). Additionally, treatment with HESI resulted in a significant increase in gastric fluid after histamine stimulation in pyloric-ligated rabbits when compared with the negative control (p<0.001). The extract of S. indicum also significantly decreased titratable acidity of histamine treated rabbits and increased gastric pH when compared with negative control (p<0.001). HESI significantly protected rabbits from ulceration after histamine administration in 4 hour pyloric ligated rabbits with a percentage protection of 79.3% (p<0.001). The extract also increased the volume of gastric fluid significantly after 4 hr pyloric ligation (p<0.01). Cimetidine protected pyloric-ligated rabbits from ulceration (92.1%) (p<0.001) and also raised the gastric pH (p<0.001), protein concentration in the gastric fluid (p<0.001), and reduced the titratable acidity (p<0.001) when compared with the negative control. The leaves of S. indicum possess gastroprotective properties. PMID- 22314988 TI - Vertical administration of vanadium through lactation induces behavioural and neuromorphological changes: protective role of vitamin E. AB - The work investigated the protective role of vitamin E on vanadium induced neurotoxicity. Three adult female rats were divided into three groups, A-C with each dam and her pups forming a group. Group A served as control. The dam in Group B was given 3mg/kg b.w./day of vanadium from PND 1 while the Group C dam were given 3mg/kg b.w./day of vanadium, for 14 days and 500mg/kg b.w. of vitamin E 72 hourly in the same time frame. The results showed that pups from Group B, exhibited behavioural deficits in most tests, a significant reduction in body weight gain and absolute brain weight; in addition immunohistochemistry showed reactive astrogliosis induced by vanadium exposure. All these findings were however attenuated in pups whose dam was exposed to vanadium and vitamin E depicting the significant protective effects of this antioxidant against vanadium. This study is novel in that both vanadium and vitamin E were introduced through the lactation route. We conclude that though caution remains essential in the posology of vitamin E, the management of lactating mothers who have been exposed to vanadium occupationally, environmentally or therapeutically with supplementation of this antioxidant may be beneficial at least in the short term to both mother and offspring. PMID- 22314989 TI - Modulatory role of ascorbic acid on behavioural responses of pigs transported by road during the harmattan season. AB - Experiments were performed on adult local pigs with the aim of investigating the modulatory role of ascorbic acid (AA) on their behavioural responses to 4-h, road transportation during the harmattan season. Sixteen adult pigs administered with AA at the dose of 250 mg/kg dissolve in sterile water served as experimental animals, and 13 others administered with sterile water were used as control animals. All the pigs were transported for 4-h at speed of 40-50 km/h covering a distance of 140 km. The behavioural activities were determined before and after road transportation. The behavioural activities were higher (P<0.05) in the experimental than control pigs immediately after transportation. In conclusion, AA ameliorates behavioural stress induced by road transportation of pigs for 4 h and may be of value in reducing adverse effects of road transportation in pigs. PMID- 22314990 TI - Pain threshold variations in female rats as a function of the estrus cycle. AB - In this study, the response of female rats in different phases of the estrus cycle to nociceptive stimulation was evaluated using thermal (hot plate and tail immersion) and chemical (formalin) tests. In the hot plate test, the paw licking latency fell significantly (p < 0.05) in the metestrus and diestrus phases compared with the proestrus and estrus phases. The observations in the tail immersion test also followed the same pattern. The significant reductions in the paw licking and tail withdrawal latencies due to a lowered threshold denote an increase in pain sensitivity in the metestrus and diestrus phases. In the formalin test, the licking time fell significantly from the metestrus to the diestrus phase compared with the proestrus and estrus phases, the reduction in this test which was due to an increased threshold connotes a decrease in pain sensitivity. The results therefore seem test dependent. In conclusion, pain threshold in female rats depends on the estrus state. PMID- 22314991 TI - Anti-nociceptive and anti-inflammatory properties of the ethanolic extract of Lagenaria breviflora whole fruit in rat and mice. AB - The present study was conducted to evaluate the anti-nociceptive and anti inflammatory properties of an ethanol extract of whole fruit of Lagenaria breviflora (LB) in rat and mice. Analgesic activity was measured by hot plate, formalin-induced paw licking, and acetic acid-induced abdominal writhing tests, while anti-inflammatory activity was determined by inhibition of carrageenan induced paw oedema. Extract-treated animals exhibited significantly (P<0.05) higher pain threshold, lower number of licking of paws in response to formalin induced irritation and writhing movements in response to acetic acid-induced writhing movement. There was significant (P<0.05) inhibition of carrageenan induced paw oedema in rats pre-treated with the extract (50, 100, 200mg/kg) by 6.4%, 27.5%, 55.9% respectively. Analgesic effect of the extract (50, 100, 200mg/kg) in hot plate test was observable within 30 minutes of administration with maximum effect obtainable 90 minutes post-administration. Also, the effect of the extract (50, 100 and 200mg/kg) was dose dependent in both the early (88.17+/-6.21, 80.33+/-3.49 and 72.33+/-5.16) and late (72.50+/-3.95, 53.83+/ 3.96 and 35.83+/-3.78) phases of formalin-induced paw licking, and in acetic acid induced writhing with inhibition of 26.8%, 48.1% and 58.1% respectively. Its effect was comparable especially at 200mg/kg body weight to those of diclofenac, indomethacin and ibuprofen. It could be suggested from the findings of this experiment that the extract may be mediating its action as a central analgesic agent but the peripheral analgesic effect was preponderant based on its outcome from the pain models. PMID- 22314992 TI - Analgesic, anti-inflammatory and antipyretic effects of the ethanol extract of Acalypha wilkesiana leaves in rats. AB - The leaves of Acalypha wilkesiana are commonly used for the treatment of pain, fever and ulcer by traditional medical practitioners without any scientific data to evaluate the appropriateness of some of the practices. Therefore, this study was carried out to determine whether the ethanol extract of Acalypha wilkesiana has analgesic, anti-inflammatory and antipyretic as well as anti-ulcer effects. The hot plate latency assay and formalin- induced paw licking models were used to evaluate analgesic effects. Animals were divided into groups comprising of five rats each. There were control (administered saline) and reference (administered indomethacin) groups. Also there were three extract groups administered 25, 50 or 100 mg/Kg body weight of extracts. Ulcer was induced using absolute ethanol followed by pylorus ligation in all animals; inflammation was induced using carrageenan while pyrexia was induced by injecting brewer's yeast intramuscularly into the dorsal part of the abdominal cavities of the rats. Different sets of rats were used for the anti-ulcer, anti-inflammatory and antipyretic studies although animal grouping for extract administration were as in analgesic studies. The results show that the extract produced dose-dependent and significant (p<0.05) analgesic and anti-inflammatory activities. The extract also significantly protected against ethanol induced ulcer. Likewise, the extract significantly (p<0.05) reduced the pyretic states of the animals. This study has therefore further provides evidences that may support the ethnomedicinal uses of the ethanolic extracts of Acalypha wilkesiana leaves. PMID- 22314993 TI - Effect of methanolic extract of Musa sapientum leaves on gastrointestinal transit time in normal and alloxan induced diabetic rats: possible mechanism of action. AB - Disorders of gastrointestinal motility have been associated with diabetes mellitus. Hyperglycaemia particularly has been reported to inhibit gastrointestinal transit time while glibenclamide, a sulphonylurea and insulin, both increased transit time. Musa sapientum has also been reported as an antidiabetic agent but there is dearth of information on the effect of this plant on gastrointestinal motility. This study was therefore carried out to investigate the effect of methanolic extract of Musa sapientum leaves (MEMSL) on gastrointestinal transit time (GITT) in male albino rats with and without hyperglycaemia and to elucidate possible mechanism by which this extract functions. Fifty five albino rats were divided into 11 groups of five animals each. All animals were fasted for 24hrs before the begining of the experiment. Group 1 served as control; while the remaining groups (2 - 11) were treated with 250mg/kg; 500mg/kg MEMSL; diabetic control; diabetic treated with 250mg/kg; 500mg/kg MEMSL; diabetic treated with glibenclamide (5mg/kg); normal rats treated with nifedipine (50mg/kg); normal rats treated with calcium chloride (CaCl2) only (10mg/kg); groups 10 and 11 were both pretreated with CaCl2 and subsequently treated with 250mg/kg and 500mg/kg MEMSL respectively. All plant extracts used for treatments were dissolved in normal saline and administered orally using orogastric tube. Charcoal meal was used as marker in the estimation of GITT. The study showed significant decrease in GITT in the normal rats treated with 250mg/kg and 500mg/kg of extract. However, in the diabetic rats treated with 500mg/kg MEMSL, there was significant increase in GITT and this is comparable with the gut response to glibenclamide (5mg/kg). Musa sapientum extract produced significant decrease in transit time in the calcium chloride pre-treated normal rats and this is comparable to the effect observed in Nifedipine treated group. The significant reduction in GITT produced by MEMSL in the normal rats reflects a strong possibility of MEMSL acting as calcium channel antagonist through the voltage gated calcium channel which may be due to the presence of alkaloids, saponins, cardenolides. There is the possibility of the extract acting as an inhibitor of potassium channel at higher concentration as observed in glibenclamide treated groups. PMID- 22314994 TI - Anti-diabetic and anti-oxidant effects of Zingiber officinale on alloxan-induced and insulin-resistant diabetic male rats. AB - This study was designed to investigate the hypoglycaemic and anti-oxidant effects of Zingiber officinale on experimentally induced diabetes mellitus using alloxan and insulin resistance. Aqueous extracts of raw ginger was administered orally at a chosen dose of 500mg/ml for a period of 4 weeks to alloxan-induced diabetic and insulin resistant diabetic rats. The experimental rats exhibited hyperglycaemia accompanied with weight loss to confirm their diabetic state. Ginger effectively reduced fasting blood glucose and malonydealdehyde levels in alloxan-induced diabetic and insulin resistant diabetic rats compared to control and ginger only treated rats. Furthermore, ginger increased serum insulin level and also enhanced insulin sensitivity in alloxan-induced diabetic and insulin resistant diabetic rats compared to control and ginger only treated rats. The results of the study clearly show that dietary ginger has hypoglycaemic effect, enhances insulin synthesis in male rats and has high antioxidant activity. One of the likely mechanisms is the action of malonydealdehyde, which acts as a scavenger of oxygen radicals. PMID- 22314995 TI - Estimation of absorbed cadmium in tissues of male and female albino rats through different routes of administration. AB - The resultant effects of cadmium exposure are seen in almost all the systems of the body, however, this study is designed to quantify its accumulation in tissues of animals exposed to cadmium. The rats were divided into two distinct groups of males and females, which were then divided into three groups, each for the monitoring of exposure. Group 1 served as control male and female and received normal rat chow and tap water. Group 2 males and females were treated with 5 mg/kg body weight of cadmium chloride (Cd) intraperitoneally for eight days while Group 3 males and females rats received 100 ppm of Cd in drinking water for 18 days. The concentrations of cadmium were analyzed in tissues (lung, stomach, kidney, heart, spleen, blood) by AAS. There were significant (P<0.05) increase in Cd (ppm) accumulation in males compared with females lungs (2.253 +/- 1.47 vs 0.317 +/- 0.001), stomach (0.187 +/- 0.094 vs 0.045 +/- 0.032) and blood (0.070 +/- 0.001 vs 0.001+/-0.001) when Cd was administered intraperitoneally. Following oral administration, there were significant (P<0.05) difference in Cd (ppm) content between males and females (kidney (0.506 +/- 0.074 vs 0.748 +/- 0.147), stomach (0.045 +/- 0.020 vs 0.001+/- 0.001) and blood (1.126 +/- 0.001 vs 0.114 +/- 0.001). Our results suggest that Cd accumulation in the various organs was sex and route of exposure-dependent in rats. PMID- 22314996 TI - Garlic and vitamin E provides antioxidant defence in tissues of female rats treated with nicotine. AB - Nicotine is known to induce oxidative stress in rat tissues and the antioxidant properties of garlic have been reported. This study was designed to determine if the peroxidative damage caused by nicotine administration can be effectively prevented with garlic juice, and vitamin E, a known antioxidant.Four groups of six rats each were divided into: Group I: (control) received 0.2ml of 0.9% normal saline, group II (received nicotine 0.6mg/kg b.w subcutaneously), group III (received nicotine 0.6mg/kg b.w + garlic juice 100mg/kg b.w orally), and group IV (received nicotine 0.6mg/kg b.w + Vitamin E 100mg/kg b.w orally). All animals were treated for 21 days. The pituitary gland, ovary, uterus, heart, liver and kidney of the animals were harvested, weighed and homogenized. Malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione (GSH) were then measured.Concentration of MDA was significantly increased in tissues of nicotine treated rats when compared with the control. In group III and IV, MDA levels were significantly reduced when compared with nicotine group. The activities of SOD and GSH significantly decreased in group II (nicotine only) rat tissues, while it was significantly increased in group III and IV rat tissues. The study showed that garlic juice extract (100mg/kg b.w) and vitamin E (100mg/kg b.w) administration prevented oxidative damage in rat tissues treated with nicotine. The study also showed that vitamin E has a more potent antioxidant activity than garlic juice in preventing nicotine induced oxidative damage in rat. PMID- 22314997 TI - Comparative study of C-reactive protein and other biochemical parameters in patients with hepatitis B and malaria in Calabar, Nigeria. AB - Serum levels of C-reactive proteins (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin and globulins were investigated using high sensitivity immunoturbidometric and colorimetric techniques in individuals with hepatitis (n=50), malaria (n=50) and 40 control subjects in age range of 30 to 65 years. The hepatitis patients had a significantly higher (P < 0.01) level of aminotransferases when compared to malaria patients and control subjects. The mean value of ALT was 103.50 +/- 71.4 IU/L and 46.72 +/-17.48 IU/L for hepatitis and malaria respectively. The values for AST were 116.76 +/- 63.27 IU/L and 57.74 IU/L +/- 15.18 IU/L for hepatitis and malaria respectively while the values for control were 34.75 +/- 14.64 and 35.25 +/- 15.56 IU/L for AST and ALT respectively. The malaria patients showed a significantly higher level (P < 0.01) of aminotransferases when compared to the control. The mean serum CRP levels were 0.71 +/- 0.11 mg/dL and 0.78 +/- 0.13 mg/dL for hepatitis and malaria respectively. These values were significantly higher (P < 0.01) than those of the controls which was 0.32 +/- 0.12 mg/dL. The values of CRP in malaria were significantly higher (P< 0.05) when compared with hepatitis. In malaria, AST correlated with CRP (r = 0.58). The mean serum proteins of hepatitis patients were significantly lower (P < 0.05) than those of the control and malaria while there were no significant differences between the total protein in malaria when compared with control. Albumin levels in both patients were significantly lower (P > 0.05) than those of the controls. The mean values were 33.40 +/- 3.40g/L and 34.47 +/- 3.56g/L for hepatitis and malaria respectively and 37.00 +/- 3.43 g/L for the control. C-reactive protein correlated negatively with albumin in malaria (r = -0.26) while albumin had a negative correlation with globulin(r = -0.36). Also albumin-globulin ratio were significantly (P < 0.05) decreased in both patients when compared with controls. This result suggests that a systemic acute phase response is present in hepatitis and malaria patients hence measurement of C-reactive proteins may be helpful in the diagnosis and management of hepatitis and malaria; especially in the malaria endemic region such as Nigeria. PMID- 22314998 TI - Mathematical modeling of the low and high affinity arabinose transport systems in Escherichia coli. AB - A mathematical model was developed for the low and high affinity arabinose transport systems in E. coli. The model is a system of three ordinary differential equations and takes the dynamics of mRNAs for the araE and araFGH proteins and the internal arabinose into account. Special attention was paid to estimate the model parameters from the literature. Our analysis and simulations suggest that the high affinity transport system helps the low affinity transport system to respond to high concentration of extracellular arabinose faster, whereas the high affinity transport system responds to a small amount of extracellular arabinose. Steady state analysis of the model also predicts that there is a regime for the extracellular concentration of arabinose where the arabinose system can show bistable behavior. PMID- 22314999 TI - Prospectively assessed early life experiences in relation to cortisol reactivity in adolescents at risk for asthma. AB - Altered cortisol reactivity in individuals with asthma likely increases the risk of inflammation in the face of stress. Understanding antecedents of cortisol reactivity enhances knowledge of factors affecting asthma. Forty-eight subjects genetically predisposed for asthma, recruited from a study that assessed them from birth, completed a laboratory stress procedure and self-report measures at ages 17-19 years. Observation and parent reports from age 0 to 2 years were used to create a parent child relationship risk variable and to define criteria for a cumulative risk variable. In repeated measures analysis of 46 adolescents, those who had experienced early parent child relationship problems, specifically insecure attachment, had an attenuated cortisol stress response, even after controlling for concurrent psychological function and recent stressors (F = 4.6, p < .005). Cortisol stress response was not related to asthma status. This study supports a relationship between the parent child relationship during the first 2 years of life and later cortisol response to stress in youth at genetic risk for asthma. PMID- 22315000 TI - Shiga toxin-producing Escherichia coli in Peruvian children with bloody diarrhea. AB - Shiga toxin-producing Escherichia coli (STEC) is not routinely sought in clinical laboratories in developing counties. Among 131 bloody diarrhea samples in Peruvian children <5 years of age, STEC was found in 9.2% and was associated with absence of fever, an observation that may increase suspicion of these pathogens. Because of the significant prevalence of STEC locally, proper diagnostics methods should be implemented in the region. PMID- 22315001 TI - Bordetella holmesii meningitis in a 12-year-old anorectic girl. AB - We describe a 12-year-old anorectic girl with Bordetella holmesii meningitis, the techniques used for its identification, and minimum inhibitory concentrations of antibiotics for 7 B. Holmesii strains collected in the Netherlands during the past 12 years. B. holmesii meningitis has not been previously reported. PMID- 22315002 TI - A proposed comprehensive classification of tuberculosis disease severity in children. AB - BACKGROUND: Tuberculosis (TB) in children has conventionally been classified as pulmonary TB (PTB) and extrapulmonary TB (EPTB) disease, including disseminated TB (TB meningitis and miliary disease). There is no existing approach that comprehensively characterizes the spectrum and severity of pediatric TB. This limits accurate classification of patients and comparison across cohorts. AIMS: To develop a classification of pediatric TB that reflects the spectrum and severity of clinical disease better than currently available approaches. METHODS: We propose a framework for the standard classification of TB disease severity in children. From a literature search, the following sources of information were used: clinical data, bacteriologic, histopathologic, and imaging data (including information from chest radiography, computerized tomography, and bronchoscopy). Each individual disease entity was systematically considered. Based on the extent and the presence of complications, each entity was then classified as "severe" or "nonsevere." As an initial application, we compared the proposed classification with the convention (PTB, EPTB) in a cohort of HIV-infected and -uninfected infants with culture-confirmed TB. Agreement between the 2 systems was poor. CONCLUSIONS: The proposed comprehensive disease classification system may more accurately reflect the clinical TB disease spectrum in children, is relevant to clinical management, and may be valuable to inform research on diagnostic tools and TB treatment strategies in children. Prospective studies are required to evaluate this approach in representative pediatric populations, correlating TB disease severity with diagnostic yield, treatment response, and application in existing and novel treatment strategies. PMID- 22315003 TI - Cerebrospinal fluid enrichment broth cultures rarely contribute to the diagnosis of bacterial meningitis. AB - This study included children undergoing lumbar puncture in the emergency department. Bacteria were isolated from 34 (1.7%) of 1898 cerebrospinal fluid (CSF) enrichment broth cultures; 30 were contaminants. The primary CSF Gram stain was negative in all specimens with a positive enrichment broth culture. Enrichment broth cultures rarely contributed to the diagnosis of bacterial meningitis, and positive CSF enrichment broth cultures contributed to diagnostic uncertainty. PMID- 22315004 TI - Outbreak of lower respiratory tract illness associated with human enterovirus 68 among American Indian children. AB - Human enterovirus 68 (EV68) infections are rarely reported. We describe a respiratory outbreak associated with EV68 among 18 children admitted to a remote Indian Health Service facility during August 11, 2010 through September 14, 2010. Clinical illness was characterized by pneumonia and wheezing. EV68 should be considered as an etiology in outbreaks of lower respiratory tract illness. PMID- 22315005 TI - Long-term effects of clearing Helicobacter pylori on growth in school-age children. AB - BACKGROUND: A new Helicobacter pylori infection affects growth velocity negatively, and clearing the infection produces a small significant rebound, but it is not known whether height and weight in children are impacted over the long term. METHODS: We investigated 295 school-age children followed in 2 cohorts, treated (150) and untreated (145), from 2004 for 3.7 years with 1105 child-years of observation. Follow-up intervals were 3 months for anthropometry measurements and 6 months for H. pylori status ascertained by urea breath test. Height in centimeters and weight in kilograms were analyzed using growth models. RESULTS: A multivariate mixed model that adjusted for age, sex, father's education, and number of siblings found no significant differences in height or weight at baseline by H. pylori status. The same model showed a significant impact of clearing H. pylori across time, with increasing significant differences in average height and weight as the follow-up progressed. CONCLUSIONS: Children who were always negative or who cleared the infection grew significantly faster than those who stayed positive after adjusting for other covariates. This study suggests that school-age children's growth benefits from being treated for H. pylori infection. PMID- 22315006 TI - Characteristics, therapies, and outcome of children with necrotizing soft tissue infections. AB - OBJECTIVES: Necrotizing soft tissue infections (NSTIs) are uncommon but potentially lethal infections that are well described in adults. Little is known about pediatric patients with NSTI. We sought to examine patients' characteristics, infection characteristics, treatment patterns, and outcomes of children with NSTIs using a large multicenter pediatric database. STUDY DESIGN: The Pediatric Health Information System database was used to examine demographics, diagnoses, procedures, medications, hospital charges, and outcomes of pediatric patients with NSTI during a 5-year period. RESULTS: A total of 334 patients with NSTI were identified. Times from admission to initial amputations and reconstructive surgeries were similar between the 2 groups, but nonsurvivors had a longer time from admission to their first debridement (median, 2 vs. 1 day, P = 0.03). On multivariate analysis, no other significant risk factors for increased mortality were identified, although increased age (P = 0.10), noncommercial insurance (P = 0.12), and use of corticosteroid therapy (P = 0.06) showed trends toward increased mortality. Diagnoses of streptococcal (P = 0.03) or staphylococcal infection (P = 0.03) were associated with a lower mortality on multivariate analysis. CONCLUSIONS: NSTIs are a rare but significant diseases in children. It seems that, as in the adult population, prompt surgical debridement is the most important intervention. Corticosteroid therapy may be associated with a worse prognosis. PMID- 22315007 TI - MicroRNA-1322 regulates ECRG2 allele specifically and acts as a potential biomarker in patients with esophageal squamous cell carcinoma. AB - A short tandem repeat (STR) polymorphism in the 3'UTR region of esophageal cancer related gene 2 (ECRG2, also known as SPINK7) has been widely reported to be associated with the incidence and the prognosis of esophageal squamous cell carcinoma (ESCC). This study explores how the microRNA binding to the STR region affects ECRG2 expression in ESCC. Dual-luciferase reporter assays were used to verify the effects of the four microRNAs (miR-580, miR-1182, miR-1272, and miR 1322) predicted to bind the STR region of the ECRG2 3' untranslated region (UTR). The expression of identified effective microRNA was then analyzed in 44 paired ESCC and adjacent normal tissues and 402 case-controlled serum samples (divided into a discovery group and an independent validation group) by real-time RT-PCR assay. We found that only miR-1322 could significantly down-regulate the ECRG2 with TCA3 allele (P < 0.01), but it could not down-regulate the ECRG2 with TCA4 allele significantly (P > 0.05). MiR-1322 was also expressed significantly higher in ESCC tissue and serum samples than in controls (both P < 0.01). Additionally, serum levels of miR-1322 yielded an under receiver operating characteristic (ROC) curve area of 0.847 (95% CI, 0.795-0.890) for discriminating ESCCs from healthy controls in the discovery group and a similar result was obtained in the validation group (under ROC area is 0.845; 95%CI, 0.780-0.897). We conclude that miR-1322 can regulate ECRG2 in an allele-specific manner and that serum levels of miR-1322 can serve as a potential diagnostic biomarker for patients with ESCC. PMID- 22315008 TI - Changes in the brain during long-term follow-up after liver transplantation. AB - PURPOSE: To examine changes in the brain before liver transplantation caused by the accumulation of paramagnetic ion deposits and to investigate recovery after liver transplantation over a long-term horizon. MATERIALS AND METHODS: Fifteen patients indicated for liver transplantation, 26 patients up to 2 years after, and 40 patients 8-15 years after liver transplantation were subjected to MR relaxometry. T(1) and T(2) relaxation times in the basal ganglia, thalamus, and white matter were evaluated. RESULTS: Relaxometry revealed a shortening of the relaxation times due to the deposition of paramagnetic ions in the basal ganglia before liver transplantation (P < 0.05), complete normalization of the relaxation times shortly after transplantation in the globus pallidus and caudate nucleus, and partial recovery of T(2) in the putamen. Relaxation times remained stable even 15 years posttransplantation. Increased relaxation times posttransplantation were found in the white matter and thalamus. CONCLUSION: The shortening of the relaxation times observed in the basal ganglia before liver transplantation was caused by paramagnetic ion deposition. The recovery observable within 2 years after transplantation was permanent, and no recurrence of paramagnetic ion deposition was observed even 15 years posttransplantation. Changes in the white matter and thalamus after transplantation were attributed to damage caused by permanent exposure to immunosuppressants. PMID- 22315009 TI - Calpain 1 and -2 play opposite roles in cord formation of lymphatic endothelial cells via eNOS regulation. AB - Calpains are a family of calcium-dependent proteases. Two isoforms, calpain 1 and 2, have been implicated in angiogenesis and endothelial cell adhesion and migration. Calpains regulate the function of eNOS;however, the relation of calpains and eNOS to lymphangiogenesisis still unclear. In the present study, we evaluated the role of calpain and eNOS in the formation of cords by lymphatic endothelial cells on Matrigel. Human lymphatic microvascular dermal-derived endothelial cells were transfected with siRNA against calpain 1 or 2. Calpain 2 knockdown, but not calpain 1 knockdown, significantly reduced cord formation, adhesion, and migration on Matrigel. These decreases correlated with a reduction in eNOS, and phosphorylated eNOS and Hsp90 levels, as assayed by immunoprecipitation and western blotting. In contrast, the knockdown of calpain 1, but not calpain 2,increased cell adhesion, enhanced migration, and stabilized late-stage cord formation by increasing cord length compared to the control. These differences correlated with an increase in the level of phosphorylated eNOS. The results indicated that the functions of calpains and eNOS are important for cord formation by lymphatic endothelial cells. For the first time, we have found different functions of calpain 1 and 2. Calpain 1 is involved in the degradation of eNOS and Hsp90 and the phosphorylation of eNOS,while calpain 2 regulates eNOS phosphorylation during cord formation by lymphatic endothelial cells on Matrigel. PMID- 22315010 TI - A palladium-catalyzed three-component reaction for the preparation of quinazolin 4(3H)-imines. AB - A novel and efficient route for the preparation of quinazolin-4(3H)-imines via a palladium-catalyzed three-component reaction of carbodiimide, isocyanide, and nucleophile is described. The palladium-catalyzed isocyanide insertion is believed to be the key step during the reaction process. PMID- 22315011 TI - The tail suspension test. AB - The tail-suspension test is a mouse behavioral test useful in the screening of potential antidepressant drugs, and assessing of other manipulations that are expected to affect depression related behaviors. Mice are suspended by their tails with tape, in such a position that it cannot escape or hold on to nearby surfaces. During this test, typically six minutes in duration, the resulting escape oriented behaviors are quantified. The tail-suspension test is a valuable tool in drug discovery for high-throughput screening of prospective antidepressant compounds. Here, we describe the details required for implementation of this test with additional emphasis on potential problems that may occur and how to avoid them. We also offer a solution to the tail climbing behavior, a common problem that renders this test useless in some mouse strains, such as the widely used C57BL/6. Specifically, we prevent tail climbing behaviors by passing mouse tails through a small plastic cylinder prior to suspension. Finally, we detail how to manually score the behaviors that are manifested in this test. PMID- 22315012 TI - EPR and speciation simulation study of Cu2+ complexes in an amine-based aqueous precursor system used for preparation of superconducting YBCO coatings. AB - In this work, we investigate the chemistry for an aqueous acetate-triethanolamine ammonia based YBa(2)Cu(3)O(7-delta) (YBCO) precursor system. These precursor solutions are suited for the chemical solution deposition of superconducting YBCO layers on top of single crystal SrTiO(3) or buffered NiW tapes. The development of this kind of precursor inks often involves trial-and-error experimenting and thus is very time-consuming. To reduce labwork to the minimum, the theoretical prediction of pH stability limits and the complexation behaviour of the different metal ions and complexants in the inks are very important. For this purpose, we simulated, based on literature values, the complexation behaviour of Cu(2+) in the aqueous precursor solutions as a function of pH. To validate the used model, we performed potentiometric pH titrations for solutions with similar composition and checked the correctness of fit between experiment and model. The generated complexometric results are coupled with X-band EPR spectra to further confirm the results. EPR spectra for fully prepared precursor solutions as well as for Cu(2+) reference solutions containing only one type of ligand (acetate, triethanolamine or ammonia) were investigated as a function of pH. We find that, in line with speciation simulation, only acetates are actively complexing the Cu(2+) ions at pH values below 7, while when reaching higher pH levels mainly triethanolamine complexes are formed. Over the entire pH range, no trace of free Cu(2+)or Cu(OH)(2), possibly creating precipitation during gelation and thus complicating further processing, could be found. PMID- 22315013 TI - Clinical-pathological changes in differentiated thyroid cancer (DTC) over time (1997-2010): data from the University Hospital "Maggiore della Carita" in Novara. AB - Differentiated thyroid cancer (DTC) is an important clinical entity in our population (Novara, Piedmont, Italy) which is characterized by important environmental influences, as iodine deficiency (ID) and subsequent supplementation, thyroiditis and occupational exposure. To evaluate the features of DTC in our population 20 years after the iodine-prophylaxis pondering the effects of the introduction of the new guidelines for diagnosis and management of DTC after 2005. 322 patients [244 females, age: mean (+/-SD) 53.8 +/- 15.8 years] treated for DTC in a tertiary care center between 1997 and 2010 were retrospectively evaluated. Medical history, demographics, and pathological features were considered. Patients were subdivided into two groups: A (n = 139, diagnosis 1997-2005) and B (n = 183, diagnosis 2006-2010). The population of group A showed a mild ID, while normal iodine status was recorded in group B. A significant increase in histological tumor-associated thyroiditis was found from group A to B (p = 0.021). Recurrent or persistent diseases were found to be correlated with lymph nodes metastases and/or a distant disease at diagnosis, stimulated thyroglobulin levels at the first follow-up and an additional radioiodine therapy. Twenty percent of our patients were females employed in textile industries. The tumor-related inflammation and the occupational exposure should be considered as important factors in the pathogenesis of DTC. Further studies are required in order to confirm our findings. PMID- 22315014 TI - The role of pro/anti-inflammatory adipokines on bone metabolism in NAFLD obese adolescents: effects of long-term interdisciplinary therapy. AB - To investigate the role of pro- and anti-inflammatory adipokines in the bone metabolism of non-alcoholic fatty liver disease (NAFLD) obese adolescents as well as the effects of long-term interdisciplinary therapy on metabolic-related risk factors. Forty post-puberty obese adolescents were randomly assigned into two groups: (1) NAFLD group and (2) non-NAFLD group (diagnosis by ultrasonography) and submitted to a weight loss therapy. Body composition was analyzed by air displacement plethysmography, bone mineral density (BMD) and content by dual energy X-ray absorptiometry, blood samples were collected to measure lipid profile, hepatic enzymes, and adipokines. Leptin and adiponectin concentrations were measured by ELISA. A decrease in total body mass, BMI, body fat, visceral and subcutaneous fat, insulin concentration, HOMA-IR, total cholesterol and an increase in lean body mass were observed in both groups after therapy. It was found positive correlation between the Delta BMD and the Delta fat mass (%) (r = 0.31, P = 0.01) and negative correlations between Delta BMC with Delta HOMA-IR (r = -0.34, P = 0.02) and Delta HOMA-IR with Delta leptin (r = -0.34, P = 0.02). In addition, increased levels of adiponectin and reduction in leptin concentrations were observed in NAFLD group. In the simple regression analysis, the HOMA-IR was an independent predictor changes in BMC in total obese adolescents and in the non NAFLD group. One year of interdisciplinary weight loss therapy for obese adolescents with or without NAFLD, could regulate bone mineral metabolism as result of an increased BMC and improved inflammatory state. PMID- 22315015 TI - In vitro siRNA-mediated knockdown of the UT receptor: implications of density on the efficacy of a range of UT ligands. AB - Urotensin-II (U-II) is the peptide agonist for the U-II receptor (UT). Putative UT antagonists, urantide and UFP-803, have been found to have variable efficacy in a range of assays. We have used siRNA-mediated RNA interference to probe the efficacy of these ligands compared to U-II. Knockdown of human UT occurs in the same cellular background with the same coupling machinery allowing relative efficacy to be probed. CHO cells stably expressing 1,110 fmol/mg protein of human UT (CHOhUT) were transfected with s194454, s194455 (UT-targeting), or a negative control siRNA using siPORT amine transfection reagent. After 48 h,silencing was assessed using quantitative PCR in a duplex assay format. Functional consequences of silencing were assessed by measuring [Ca2+]i in Fura-2 loaded cells using the NOVOstar plate reader. Silencing with s194455 was greater than that with s194454 (93.5+/-2.8% and 73.0+/-2.5%knockdown of UT mRNA respectively at 10-7 M, p00.006).Both s194455 and s194454 knocked down UT mRNA expression with equal potency (EC50 1.38 and 0.45 nM). The negative control did not affect UT mRNA expression. U-II(10-6M) increased [Ca2+]i 630+/-69, 402+/-49 and 190+/ 14nM,urantide (10-6 M) increased [Ca2+]i 408+/-55, 191+/-40, and 131+/-10 nM and UFP-803 (10-6 M) increased [Ca2+]i 134+/-23, 83+/-11 and 53+/-3nM for negative control siRNA, s194454 and s194455, respectively.We have demonstrated silencing of UT mRNA and a reduction of absolute efficacy of three UT ligands. However, we were unable to resolve any changes in relative efficacy for urantide and UFP-803. This is likely to result from a high starting expression and retention of a receptor/coupling reserve. PMID- 22315016 TI - Proteins derived from latex of C. procera maintain coagulation homeostasis in septic mice and exhibit thrombin- and plasmin-like activities. AB - The proteins derived from the latex (LP) of Calotropis procera are well known for their anti-inflammatory property. In view of their protective effect reported in the sepsis model, they were evaluated for their efficacy in maintaining coagulation homeostasis in sepsis. Intraperitoneal injection of LP markedly reduced the procoagulation and thrombocytopenia observed in mice infected with Salmonella; while in normal mice, LP produced a procoagulant effect. In order to understand its mechanism of action, the LP was subjected to ion-exchange chromatography, and the three subfractions (LPPI, LPPII, and LPPIII) thus obtained were tested for their proteolytic effect and thrombin- and plasmin-like activities in vitro. Of the three subfractions tested, LPPII and LPPIII exhibited proteolytic effect on azocasein and exhibited procoagulant effect on human plasma in a concentration-dependent manner. Like trypsin and plasmin, these subfractions produced both fibrinogenolytic and fibrinolytic effects that were mediated through the hydrolysis of the Aalpha, Bbeta, and gamma chains of fibrinogen and alpha-polymer and gamma-dimer of fibrin clot, respectively. This study shows that the cysteine proteases present in the latex of C. procera exhibit thrombin- and plasmin-like activities and suggests that these proteins have therapeutic potential in various conditions associated with coagulation abnormalities. PMID- 22315017 TI - Does public disclosure of quality indicators influence hospitals' inclination to enhance results? AB - OBJECTIVE: The national guideline on oesophageal carcinoma's recommendation of a minimum number of 10 resections per year and the intervention of the Dutch Health Care Inspectorate have highlighted hospitals' 'need to score' on the public quality indicator for the annual number of oesophageal resections. To determine whether low-volume hospitals are inclined to adjust their numbers, we studied the difference between the reported and actual numbers of oesophageal resections in 2005 and 2006. DESIGN: A retrospective cohort study. Hospitals were asked to submit all operative reports on resections from 2005 to 2006. Two pairs of evaluators independently labelled all anonymous operative reports from the selected hospitals as resection or non-resection. SETTING: Hospitals in the Netherlands. PARTICIPANTS: Ten hospitals that reported 10 or 11 resections in 2006, or an average of fewer than 10 resections per year in the period 2003-2006. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Difference between the reported and actual numbers of oesophageal resections in 2005 and 2006. RESULTS: Oesophageal resection criteria were not met in 7% of the 179 operative reports from the 10 selected hospitals. The difference between the reported and actual numbers of resections in 2005 was not significant, while in 2006 it was. Of the hospitals studied, 70% actually performed fewer resections than they reported. CONCLUSION: Our results support the assumption that low-volume hospitals are inclined to adjust their numbers when, because outcomes are public, pressure to report a sufficient number is high. So, external verification of data is essential when this 'need to score' is high. PMID- 22315019 TI - AAPSConnection. PMID- 22315018 TI - Primary and secondary reference materials for procedures to test the quality of medicines and foods. AB - At present a complex global patchwork of private and public monographs and reference materials is variously available to help ensure the quality of medicines and foods. The relationship of these monographs and reference materials, one to another, frequently is inconsistently understood and documented.This article considers the complexity of monographs and reference materials with a focus on qualifying one reference material relative to another. PMID- 22315020 TI - Solution behavior of PVP-VA and HPMC-AS-based amorphous solid dispersions and their bioavailability implications. AB - PURPOSE: To identify the mechanism behind the unexpected bio-performance of two amorphous solid dispersions: BMS-A/PVP-VA and BMS-A/HPMC-AS. METHODS: Solubility of crystalline BMS-A in PVP-VA and HPMC-AS was measured by DSC. Drug-polymer interaction parameters were obtained by Flory-Huggins model fitting. Drug dissolution kinetics of spray-dried dispersions were studied under sink and non sink conditions. BMS-A supersaturation was studied in the presence of pre dissolved PVP-VA and HPMC-AS. Potency and crystallinity of undissolved solid dispersions were determined by HPLC and DSC. Polymer dissolution kinetics were obtained by mass balance calculation. Bioavailability of solid dispersions was assessed in dogs. RESULTS: In solid state, both polymers are miscible with BMS-A, while PVP-VA solublizes the drug better. BMS-A dissolves similarly from both solid dispersions in vitro regardless of dissolution method, while the HPMC-AS dispersion performed much better in vivo. At the same concentration, HPMC-AS is more effective in prolonging BMS-A supersaturation; this effect was negated by the slow dissolution rate of HPMC-AS. Further study revealed that fast PVP-VA dissolution resulted in elevated drug loading in undissolved dispersions and facilitated drug recrystallization before complete release. In contrast, the hydrophobicity and slower HPMC-AS dissolution prevented BMS-A recrystallization within the HPMC-AS matrix for >24 h. CONCLUSIONS: The lower bioavailability of PVP-VA dispersion was attributed to BMS-A recrystallization within the undissolved dispersion, due to hydrophilicity and fast PVP-VA dissolution rate. Polymer selection for solid dispersion development has significant impact on in vivo performance besides physical stability. PMID- 22315021 TI - Dehydration kinetics and crystal water dynamics of carbamazepine dihydrate. AB - PURPOSE: To investigate the dehydration of carbamazepine dihydrate, combining kinetics and crystal water dynamics with electronic structure calculations. METHODS: Thermal microscopy, moisture sorption, and thermogravimetric analysis (TGA) were applied to evaluate the effects on relative humidity (RH) and temperature, while crystal water dynamics were monitored by 2D-FTIR correlation spectroscopy (2DCOS) and the nature of the H-bonding network was investigated by 3D-periodic DFT calculations. RESULTS: It was found that the dihydrate is unstable below 40% RH and/or above the glass transition temperature (T g ~ 53 degrees C). At room temperature, amorphous carbamazepine is formed at RH ~ 0%, form I at RH ~ 10%, and mixtures of forms I and III at higher RH. Above the T g , the dehydration yields partially crystalline mixtures of forms I and IV between 50-100 degrees C, and form I above 100 degrees C. In all cases, the amorphous product crystallizes to form IV. Thermal analysis and 2DCOS revealed a biphasic dehydration process. Kinetic modelling suggests a diffusion-controlled dehydration below T g and reaction interface-controlled kinetics above T g . CONCLUSIONS: The dehydration consists of two overlapping water removal processes, with the water molecule attached to the amide C=O departing faster, probably due to the destabilizing effect of anti-bonding interactions between the water H1s and the carbonyl O2p orbital. PMID- 22315022 TI - Hybrid computational phantoms representing the reference adult male and adult female: construction and applications for retrospective dosimetry. AB - Currently, two classes of computational phantoms have been developed for dosimetry calculation: (1) stylized (or mathematical) and (2) voxel (or tomographic) phantoms describing human anatomy through mathematical surface equations and 3D voxel matrices, respectively. Mathematical surface equations in stylized phantoms are flexible, but the resulting anatomy is not as realistic. Voxel phantoms display far better anatomical realism, but they are limited in terms of their ability to alter organ shape, position, and depth, as well as body posture. A new class of computational phantoms called hybrid phantoms takes advantage of the best features of stylized and voxel phantoms-flexibility and anatomical realism, respectively. In the current study, hybrid computational phantoms representing the adult male and female reference anatomy and anthropometry are presented. These phantoms serve as the starting framework for creating patient or worker sculpted whole-body phantoms for retrospective dose reconstruction. Contours of major organs and tissues were converted or segmented from computed tomography images of a 36-y-old Korean volunteer and a 25-y-old U.S. female patient, respectively, with supplemental high-resolution CT images of the cranium. Polygon mesh models for the major organs and tissues were reconstructed and imported into RhinocerosTM for non-uniform rational B-spline (NURBS) surface modeling. The resulting NURBS/polygon mesh models representing body contour and internal anatomy were matched to anthropometric data and reference organ mass data provided by Centers for Disease Control and Prevention and International Commission on Radiation Protection, respectively. Finally, two hybrid adult male and female phantoms were completed where a total of eight anthropometric data categories were matched to standard values within 4% and organ volumes matched to ICRP data within 1% with the exception of total skin. The hybrid phantoms were voxelized from the NURBS phantoms at resolutions of 0.158 * 0.158 * 0.158 cm and 0.126 * 0.126 * 0.126 cm for the male and female, respectively. To highlight the flexibility of the hybrid phantoms, graphical displays are given of (1) underweight and overweight adult male phantoms, (2) a sitting position for the adult female phantom, and (3) extraction and higher resolution voxelization of the small intestine for localized dosimetry of mucosal and stem cell layers. These phantoms are used to model radioactively contaminated individuals and to then assess time-dependent detector count rate thresholds corresponding to 50, 250, and 500 mSv effective dose, as might be needed during in-field radiological triage by first responders or first receivers. PMID- 22315023 TI - The stochastic nature of all radiation effects. PMID- 22315025 TI - Is there really any risk from radon? PMID- 22315027 TI - Natural vs. artificial anthropometric phantoms for measuring bone-seeking radionuclides. PMID- 22315032 TI - Health physics society * 2012 affiliate members. PMID- 22315033 TI - Minimally invasive anterior transarticular screw fixation and microendoscopic bone graft for atlantoaxial instability. AB - PURPOSE: Even though transarticular screw (TAS) fixation has been commonly used for posterior C1-C2 arthrodesis in both traumatic and non-traumatic lesions, anterior TAS fixation C1-2 is a less invasive technique as compared with posterior TAS which produces significant soft tissue injury, and there were few reports on percutaneous anterior TAS fixation and microendoscopic bone graft for atlantoaxial instability. The goals of our study were to describe and evaluate a new technique for anterior TAS fixation of the atlantoaxial joints for traumatic atlantoaxial instability by analyzing radiographic and clinical outcomes. METHODS: This was a retrospective study of seven consecutive patients with C1-C2 instability due to upper cervical injury treated by a minimally invasive procedure from May 2007 to August 2009. Bilateral anterior TAS were inserted by the percutaneous approach under Iso-C3D fluoroscopic control. The atlantoaxial joint space was prepared for morselized autogenous bone graft under microendoscopy. The data for analysis included time after the injuries, operating time, intraoperative blood loss, X-ray exposure time, clinical results, and complications. Radiographic evaluation included the assessment of atlantoaxial fusion rate and placement of TAS. Bone fusion of the atlantoaxial joints was assessed by flexion extension lateral radiographs and 1-mm thin-slice computed tomography images as radiographic results. Clinical assessment was done by analyzing the recovery state of clinical presentation from the preoperative period to the last follow-up and by evaluating complications. RESULTS: A total of 14 screws were placed correctly. The atlantoaxial solid fusion without screw failure was confirmed by CT scan in seven cases after a mean follow-up of 27.5 months (range 18-45 months). All patients with associated clinical presentation made a recovery without neurologic sequelae. Postoperative dysphagia occurred and disappeared in two cases within 5 days after surgery. There were no other complications during the follow-up period. CONCLUSIONS: Percutaneous anterior TAS fixation and microendoscopic bone graft could be an option for achieving C1-C2 stabilization with several potential advantages such as less tissue trauma and better accuracy. Bilateral TAS fixation and morselized autograft affords effective fixation and solid fusion by a minimally invasive approach. PMID- 22315034 TI - Intraoperative determination of the load-displacement behavior of scoliotic spinal motion segments: preliminary clinical results. AB - INTRODUCTION: Spinal fusion is a widely and successfully performed strategy for the treatment of spinal deformities and degenerative diseases. The general approach has been to stabilize the spine with implants so that a solid bony fusion between the vertebrae can develop. However, new implant designs have emerged that aim at preservation or restoration of the motion of the spinal segment. In addition to static, load sharing principles, these designs also require a profound knowledge of kinematic and dynamic properties to properly characterise the in vivo performance of the implants. METHODS: To address this, an apparatus was developed that enables the intraoperative determination of the load-displacement behavior of spinal motion segments. The apparatus consists of a sensor-equipped distractor to measure the applied force between the transverse processes, and an optoelectronic camera to track the motion of vertebrae and the distractor. In this intraoperative trial, measurements from two patients with adolescent idiopathic scoliosis with right thoracic curves were made at four motion segments each. RESULTS: At a lateral bending moment of 5 N m, the mean flexibility of all eight motion segments was 0.18 +/- 0.08 degrees /N m on the convex side and 0.24 +/- 0.11 degrees /N m on the concave side. DISCUSSION: The results agree with published data obtained from cadaver studies with and without axial preload. Intraoperatively acquired data with this method may serve as an input for mathematical models and contribute to the development of new implants and treatment strategies. PMID- 22315035 TI - Sagittal endplate morphology of the lower lumbar spine. AB - SUMMARY OF BACKGROUND DATA: The sagittal profile of lumbar endplates is discrepant from current simplified disc replacement and fusion device design. Endplate concavity is symmetrical in the coronal plane but shows considerable variability in the sagittal plane, which may lead to implant-endplate mismatch. OBJECTIVE: The aim of this investigation is to provide further analysis of the sagittal endplate morphology of the mid to lower lumbar spine study (L3-S1), thereby identifying the presence of common endplate shape patterns across these levels and providing morphological reference values complementing the findings of previous studies. STUDY DESIGN: Observational study. METHODS: A total of 174 magnetic resonance imaging (MRI) scans of the adult lumbar spine from the digital archive of our centre, which met the inclusion criteria, were studied. Superior (SEP) and inferior (IEP) endplate shape was divided into flat (no concavity), oblong (homogeneous concavity) and ex-centric (inhomogeneous concavity). The concavity depth (ECD) and location of concavity apex (ECA) relative to endplate diameter of the vertebrae L3-S1 were determined. RESULTS: Flat endplates were only predominant at the sacrum SEP (84.5%). The L5 SEP was flat in 24.7% and all other endplates in less than 10%. The majority of endplates were concave with a clear trend of endplate shape becoming more ex-centric from L3 IEP (56.9% oblong vs. 37.4% ex-centric) to L5 IEP (4% oblong vs. 94.3% ex-centric). Ex-centric ECA were always found in the posterior half of the lumbar endplates. Both the oblong and ex-centric ECD was 2-3 mm on average with the IEP of a motion segment regularly possessing the greater depth. A sex- or age-related difference could not be found. CONCLUSION: The majority of lumbar endplates are concave, while the majority of sacral endplates are flat. An oblong and an ex-centric endplate shape can be distinguished, whereby the latter is more common at the lower lumbar levels. The apex of the concavity of ex-centric discs is located in the posterior half of the endplate and the concavity of the inferior endplate is deeper than that of the superior endplate. Based on the above, the current TDR and ALIF implant design does not sufficiently match the morphology of lumbar endplates in the sagittal plane. PMID- 22315036 TI - Analysis of internal construct validity of the SRS-24 questionnaire. AB - PURPOSE: The SRS-24 questionnaire was originally validated using methods of classical test theory, but internal construct validity has never been shown. Internal construct validity, i.e. unidimensionality and linearity, is a fundamental arithmetic requirement and needs to be shown for a scale for summating any set of Likert-type items. Here, internal construct validity of the SRS-24 questionnaire in adolescent idiopathic scoliosis (AIS) patients is analyzed. METHODS: 232 SRS-24 questionnaires distributed to 116 patients with AIS pre-operatively and at postoperative follow-up were analyzed. 103 patients were females; the average age was 16.5 +/- 7.1 years. The questionnaires were subjected to Rasch analysis using the RUMM2020 software package. RESULTS: All seven domains of the SRS-24 showed misfit to the Rasch model, and three of seven were unidimensional. Unidimensionality and linearity could only be achieved for an aggregate score by separating pre- and postoperative items and omitting items which caused model misfit. Reducing the questionnaire to six pre-operative items (p = 0.098; 2.25% t tests) and five postoperative items (p = 0.267; 3.70% t tests) yields model fit and unidimensionality for both summated scores. The person-separation indices (PSI) were 0.67 and 0.69, respectively, for the pre- and postoperative patients. CONCLUSIONS: The SRS-24 score is a non-linear and multidimensional construct. Adding the items into a single value is therefore not supported and invalid in principle. Making profound changes to the questionnaire yields a score which fulfills the properties of internal construct validity and supports its use a change score for outcome measurement. PMID- 22315038 TI - Asymmetric osteotomy of the spine for coronal imbalance: a technical report. AB - STUDY DESIGN: Technical report on the surgical technique of asymmetric osteotomy of the spine for coronal imbalance. OBJECTIVE: To describe a successful method of performing asymmetrical pedicle subtraction osteotomy (APSO) through a posterior only approach. SUMMARY OF BACKGROUND: Rigid coronal deformity of the spine can be sharply angulated and can create significant coronal imbalance. Surgical correction is the only definitive treatment of restoring the balance as bracing is unhelpful. Corrective surgery can be anterior or posterior. The literature on the methods of surgical correction of rigid coronal deformities of the spine is limited. Unlike osteotomies for sagittal imbalance, blunt dissection of the anterior cortex is necessary in asymmetrical osteotomy to allow resection of the anterior cortex for closure of the wedge. We describe a method by which we performed this in the thoracic and lumbar spine with case examples. METHOD: After insertion of pedicle screws, laminectomy and unilateral facetectomy of the proposed level of osteotomy is performed. Next, dissection lateral to the pedicle and vertebral body is performed bluntly with mastoids to reach the front of the anterior cortex and confirmed with fluoroscopy. An oblique osteotomy including the lateral and posterior cortex is performed above and below the pedicle under imaging. The osteotomy site is closed through unilateral compression. CONCLUSION: Satisfactory correction of coronal deformity can be achieved with APSO from an isolated posterior approach. In contrast to sagittal osteotomies, blunt dissection along the anterior cortex is necessary to allow safe resection of anterior cortical bone for closure of the wedge. PMID- 22315039 TI - Twist angle perturbation on mixed (phthalocyaninato)(porphyrinato) dysprosium(III) double-decker SMMs. AB - Correlation between molecular structures and slow relaxation of magnetization of three mixed (phthalocyaninato)(porphyrinato) dysprosium(III) double-deckers clearly reveals the effect of the sandwich-type molecular structure, in particular the twist angle, on the quantum tunneling (QT) at zero dc field of these complexes, providing the first direct evidence to the theoretical inference. PMID- 22315040 TI - Proteomic analysis in clear cell renal cell carcinoma: identification of differentially expressed protein by 2-D DIGE. AB - Renal cell carcinoma (RCC), the most common neoplasm affecting the adult kidney, is characterised by heterogeneity of histological subtypes, drug resistance, and absence of molecular markers. Two-dimensional difference gel electrophoresis (2-D DIGE) technology in combination with mass spectrometry (MS) was applied to detect differentially expressed proteins in 20 pairs of RCC tissues and matched adjacent normal kidney cortex (ANK), in order to search for RCC markers. After gel analysis by DeCyder 6.5 and EDA software, differentially expressed protein spots were excised from Deep Purple stained preparative 2DE gel. A total of 100 proteins were identified by MS out of 2500 spots, 23 and 77 of these were, respectively, over- and down-expressed in RCC. The Principal Component Analysis applied to gels and protein spots exactly separated the two sample classes in two groups: RCC and ANK. Moreover, some spots, including ANXA2, PPIA, FABP7 and LEG1, resulted highly differential. The DIGE data were also confirmed by immunoblotting analysis for these proteins. In conclusion, we suggest that applying 2-D DIGE to RCC may provide the basis for a better molecular characterization and for the discovery of candidate biomarkers. PMID- 22315041 TI - Late-onset growing pains. PMID- 22315042 TI - Coming out of the Nkuta: disclosure of sexual orientation associated with reduced risk behavior among MSM in Cameroon. PMID- 22315043 TI - Association of serotonin transporter gene polymorphism 5-HTTLPR and depressive disorder in a Mexican population. PMID- 22315044 TI - Prenatal cortisol exposure predicts infant cortisol response to acute stress. AB - Experimental animal findings suggest that early stress and glucocorticoid exposure may program the function of the hypothalamic-pituitary-adrenal (HPA) axis in the offspring. The extension of these findings to human development is not yet clear. A prospective longitudinal study was conducted on 125 mothers and their normally developing children. Amniotic fluid was obtained at, on average, 17.2 weeks gestation; infant behavior and cortisol response to a separation reunion stress was assessed at 17 months. Amniotic fluid cortisol predicted infant cortisol response to separation-reunion stress: infants who were exposed to higher levels of cortisol in utero showed higher pre-stress cortisol values and blunted response to stress exposure. The association was independent of prenatal, obstetric, and socioeconomic factors and child-parent attachment. The findings provide some of the strongest data in humans that HPA axis functioning in the child may be predicted from prenatal cortisol exposure. PMID- 22315045 TI - Triptolide inhibits colon cancer cell proliferation and induces cleavage and translocation of 14-3-3 epsilon. AB - Triptolide is a diterpenoid triepoxide derived from the traditional Chinese medical herb Tripterygium wilfordii. In the present study, we demonstrated that this phytochemical attenuated colon cancer growth in vitro and in vivo. Using a proteomic approach, we found that 14-3-3 epsilon, a cell cycle- and apoptosis related protein, was altered in colon cancer cells treated with triptolide. In this regard, triptolide induced cleavage and perinuclear translocation of 14-3-3 epsilon. Taken together, our findings suggest that triptolide may merit investigation as a potential therapeutic agent for colon cancer, and its anticancer action may be associated with alteration of 14-3-3 epsilon. PMID- 22315046 TI - Iron(II)-catalyzed enantioselective meso-epoxide-opening with anilines. AB - A highly enantioselective method for the catalytic opening of aromatic meso epoxides with aniline derivatives was developed. The desired chiral beta-amino alcohols were obtained in mostly good to very good yields with excellent enantioselectivities. Structural evidence of the pre-catalyst revealed a scarcely disclosed heptadentate Fe(II) complex with the chiral bipyridine ligand. PMID- 22315047 TI - Direct reaction of iodine-activated lanthanoid metals with 2,6-diisopropylphenol. AB - Rare earth metals activated with ca. 2% iodine react directly with 2,6 diisopropylphenol (HOdip) in tetrahydrofuran (thf), 1,2-dimethoxyethane (dme), and dig-dme (dig = di(2-methoxyethyl) ether) to give solvated phenolate complexes [Ln(Odip)(3)(thf)(n)] (Ln = La, Nd, n = 3; Ln = Sm, Dy, Y, Yb, n = 2), [Eu(Odip)(MU-Odip)(thf)(2)](2), [Ln(Odip)(3)(dme)(2)] (Ln = La, Yb) and [La(Odip)(3)(dig)] in good yield for Ln = La, Nd, Eu but modest yield for smaller Ln metals under comparable conditions. However, increasing the excess of metal greatly increased the yield for Ln = Y. The synthetic method has general potential, at least for lanthanoid phenolates. Comparison redox transmetallation/protolysis (RTP) reactions between Ln metals, Hg(C(6)F(5))(2) and the phenol gave higher yields in shorter time and, for Eu, gave [Eu(Odip)(3)(thf)(3)] in contrast to an Eu(II) complex from Eu(I(2)). New [Ln(Odip)(3)(thf)(3)] complexes have fac-octahedral structures and [Ln(Odip)(3)(thf)(2)] monomeric five coordinate distorted trigonal bipyramidal structures with apical thf ligands. [Eu(Odip)(MU-Odip)(thf)(2)](2) is an unsymmetrical dimer with two bridging Odip ligands. One five coordinate Eu atom has distorted trigonal bipyramidal stereochemistry and the other is distorted square pyramidal. Whilst [La(Odip)(3)(dme)(2)] has irregular seven coordination with mer-Odip and chelating dme ligands, [Ln(Odip)(3)(dme)(2)] (Ln = Dy, Y (prepared by ligand exchange), Yb) are monomeric six coordinate with one chelating and one unidentate dme. A six coordinate fac-octahedral arrangement is observed in [La(Odip)(3)(dig)]. PMID- 22315048 TI - Effects of coffee on driving performance during prolonged simulated highway driving. AB - RATIONALE: Coffee is often consumed to counteract driver sleepiness. There is limited information on the effects of a single low dose of coffee on prolonged highway driving in non-sleep deprived individuals. OBJECTIVES: The aim of this study was to examine the effects of a single cup of coffee (80 mg caffeine) on simulated highway driving performance. METHODS: Non-sleep deprived healthy volunteers (n024) participated in a double-blind, placebo-controlled, crossover study. After 2 h of monotonous highway driving, subjects received caffeinated or decaffeinated coffee during a 15-min break before continuing driving for another 2 h. The primary outcome measure was the standard deviation of lateral position (SDLP), reflecting the weaving of the car. Secondary outcome measures were speed variability, subjective sleepiness, and subjective driving performance. RESULTS: The results showed that caffeinated coffee significantly reduced SDLP as compared to decaffeinated coffee, both in the first (p00.024) and second hour (p00.019) after the break. Similarly, the standard deviation of speed (p0 0.024; p00.001), mental effort (p00.003; p00.023), and subjective sleepiness (p00.001; p00.002) were reduced in both the first and second hour after consuming caffeinated coffee. Subjective driving quality was significantly improved in the first hour after consuming caffeinated coffee (p00.004). CONCLUSIONS: These findings demonstrate a positive effect of one cup of caffeinated coffee on driving performance and subjective sleepiness during monotonous simulated highway driving. PMID- 22315049 TI - Concentrations of IGF-I and IGFBP-3 and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition. AB - BACKGROUND: Insulin-like growth factors (IGFs) and their binding proteins (BPs) regulate cell differentiation, proliferation and apoptosis, and may have a role in the aetiology of various cancers. Information on their role in pancreatic cancer is limited and was examined here in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. METHODS: Serum concentrations of IGF-I and IGFBP-3 were measured using enzyme-linked immunosorbent assays in 422 cases and 422 controls matched on age, sex, study centre, recruitment date, and time since last meal. Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounding variables. RESULTS: Neither circulating levels of IGF-I (OR=1.21, 95% CI 0.75-1.93 for top vs bottom quartile, P-trend 0.301), IGFBP-3 (OR=1.00, 95% CI 0.66-1.51, P-trend 0.79), nor the molar IGF-I/IGFBP-3 ratio, an indicator of free IGF-I level (OR=1.22, 95% CI 0.75-1.97, P-trend 0.27), were statistically significantly associated with the risk of pancreatic cancer. In a cross-classification, however, a high concentration of IGF-I with concurrently low levels of IGFBP-3 was related to an increased risk of pancreatic cancer (OR=1.72, 95% CI 1.05-2.83; P-interaction=0.154). CONCLUSION: On the basis of these results, circulating levels of components of the IGF axis do not appear to be the risk factors for pancreatic cancer. However, on the basis of the results of a subanalysis, it cannot be excluded that a relatively large amount of IGF-1 together with very low levels of IGFBP-3 might still be associated with an increase in pancreatic cancer risk. PMID- 22315050 TI - Immunohistochemical discrimination of wild-type EGFR from EGFRvIII in fixed tumour specimens using anti-EGFR mAbs ICR9 and ICR10. AB - BACKGROUND: The human epidermal growth factor receptor (EGFR) is an important therapeutic target in oncology, and three different types of EGFR inhibitors have been approved for the treatment of cancer patients. However, there has been no clear association between the expression levels of EGFR protein in the tumours determined by the FDA-approved EGFR PharmDx kit (Dako) or other standard anti EGFR antibodies and the response to the EGFR inhibitors. METHOD: In this study, we investigated the potential of our anti-EGFR monoclonal antibodies (mAbs; ICR9, ICR10, ICR16) for immunohistochemical diagnosis of wild-type EGFR and/or the type III deletion mutant form of EGFR (EGFRvIII) in formalin-fixed, paraffin-embedded human tumour specimens. RESULTS: We found that the anti-EGFR mAb in the EGFR PharmDx kit stained both wild-type and EGFRvIII-expressing cells in formalin fixed, paraffin-embedded sections. This pattern of EGFR immunostaining was also found with our anti-EGFR mAb ICR16. In contrast, mAbs ICR10 and ICR9 were specific for the wild-type EGFR. CONCLUSION: We conclude that mAbs ICR9 and ICR10 are ideal tools for investigating the expression patterns of wild-type EGFR protein in tumour specimens using immunohistochemistry, and to determine their prognostic significance, as well as predictive value for response to therapy with EGFR antibodies. PMID- 22315051 TI - Prognostic significance of gamma-glutamyltransferase in patients with endometrial cancer: a multi-centre trial. AB - BACKGROUND: Gamma-glutamyltransferase (GTT), a known marker for apoptotic balance, seems to promote tumour progression, invasion and drug resistance. Recently, high GGT serum levels were shown to be associated with impaired prognosis in patients with cervical cancer. The aim of this study was to investigate the value of pre-therapeutic serum GGT levels as prognostic parameter in patients with endometrial cancer. METHODS: Within the present multi-centre trial, clinical-pathological parameters and pre-therapeutic serum GGT levels were evaluated in 874 consecutive patients with endometrial cancer. Patients were stratified in GGT risk groups, and univariate and multivariable survival analyses were performed. RESULTS: Mean pre-therapeutic serum GGT level was 30.8 (41.5) U l(-1). Elevated and highly elevated serum GGT levels (P=0.03 and P=0.005), tumour stage (P<0.001 and P<0.001), grade (P<0.001 and P=0.02) and age (P<0.001 and P<0.001) were independently associated with progression-free survival in univariate and multivariable survival analyses. Pre-therapeutic GGT was not associated with advanced tumour stage (P=0.6), higher histological grade (P=0.6) or unfavourable histological subtype (P=0.3). CONCLUSION: Pre-therapeutic serum GGT is a novel and independent prognostic parameter for progression-free survival of patients with endometrial cancer. Stratifying patients into prognostic subgroups could be used for patient counselling and individualised treatment planning. PMID- 22315053 TI - Pre-treatment lactate dehydrogenase levels as predictor of efficacy of first-line bevacizumab-based therapy in metastatic colorectal cancer patients. AB - BACKGROUND: Lactate dehydrogenase (LDH) represents a predictive factor in colorectal cancer patients treated with the angiogenesis inhibitor PTK/ZK. We explored the role of pre-treatment LDH serum levels in colorectal cancer patients receiving first-line bevacizumab. METHODS: Metastatic colorectal cancer treated with first-line bevacizumab was eligible. A control group including all consecutive patients treated with chemotherapy alone was also considered. Pre treatment LDH serum levels were collected for all cases. RESULTS: Median progression-free survival (PFS) in the control group for patients with high and low LDH levels was 4.2 and 8 months, respectively (P=0.0003). Median overall survival (OS) was 19.6 and 34.9 months for patients with high and low LDH levels, respectively (P=0.0014). In the bevacizumab group, partial responses were seen in 14 (58%) high-LDH and 8 (14%) low-LDH patients (P=0.0243), respectively, median PFS was 7.3 and 8.5 months, respectively (P=0.2), and median OS was 22 and 26.6 months, respectively (P=0.7). CONCLUSION: High LDH levels correlated with worse prognosis. Bevacizumab seemed capable of improving clinical outcome in this specific group of patients who usually present with an adverse natural history. The improved response rate also suggests a role for LDH as a predictive marker. PMID- 22315052 TI - Direct improvement of quality of life using a tailored quality of life diagnosis and therapy pathway: randomised trial in 200 women with breast cancer. AB - BACKGROUND: Despite thousands of papers, the value of quality of life (QoL) in curing disease remains uncertain. Until now, we lacked tools for the diagnosis and specific treatment of diseased QoL. We approached this problem stepwise by theory building, modelling, an exploratory trial and now a definitive randomised controlled trial (RCT) in breast cancer, whose results we report here. METHODS: In all, 200 representative Bavarian primary breast cancer patients were recruited by five hospitals and treated by 146 care professionals. Patients were randomised to either (1) a novel care pathway including diagnosis of 'diseased' QoL (any QoL measure below 50 points) using a QoL profile and expert report sent to the patient's coordinating practitioner, who arranged QoL therapy consisting of up to five standardised treatments for specific QoL defects or (2) standard postoperative care adhering to the German national guideline for breast cancer. The primary end point was the proportion of patients in each group with diseased QoL 6 months after surgery. Patients were blinded to their allocated group. RESULTS: At 0 and 3 months after surgery, diseased QoL was diagnosed in 70% of patients. The QoL pathway reduced rates of diseased QoL to 56% at 6 months, especially in emotion and coping, compared with 71% in controls (P=0.048). Relative risk reduction was 21% (95% confidence interval (CI): 0-37), absolute risk reduction 15% (95% CI: 0.3-29), number needed to treat (NNT)=7 (95% CI: 3 37). When QoL therapy finished after successful treatment, diseased QoL often returned again, indicating good responsiveness of the QoL pathway. CONCLUSION: A three-component outcome system including clinician-derived objective, patient reported subjective end points and qualitative analysis of clinical relevance was developed in the last 10 years for cancer as a complex intervention. A separate QoL pathway was implemented for the diagnosis and treatment of diseased QoL and its effectiveness tested in a community-based, pragmatic, definitive RCT. While the pathway was active, it was effective with an NNT of 7. PMID- 22315054 TI - Malignant mesotheliomas in former miners and millers of crocidolite at Wittenoom (Western Australia) after more than 50 years follow-up. AB - BACKGROUND: To report the number of malignant pleural and peritoneal mesotheliomas that have occurred in former Wittenoom crocidolite workers to the end of 2008, to compare this with earlier predictions, and to relate the mesothelioma rate to amount of exposure. METHODS: A group of 6489 men and 419 women who had worked for the company operating the former Wittenoom crocidolite mine and mill at some time between 1943 and 1966 have been followed up throughout Australia and Italy to the end of 2008. RESULTS: The cumulative number of mesotheliomas up to 2008 was 316 in men (268 pleural, 48 peritoneal) and 13 (all pleural) in women. There had been 302 deaths with mesothelioma in men and 13 in women, which was almost 10% of all known deaths. Mesothelioma rate, both pleural and peritoneal, increased with time since first exposure and appeared to reach a plateau after about 40 to 50 years. The mesothelioma rate increased with amount of exposure and the peritoneal mesotheliomas occurred preferentially in the highest exposure group, 37% compared with 15% overall. CONCLUSION: By the end of 2008, the number of mesothelioma deaths had reached 4.7% for all the male workers and 3.1% for the females. Over the past 8 years the numbers were higher than expected. It is predicted that about another 60 to 70 deaths with mesothelioma may occur in men by 2020. PMID- 22315055 TI - Socioeconomic position, treatment, and survival of non-Hodgkin lymphoma in Denmark--a nationwide study. AB - BACKGROUND: Not all patients have benefited equally from the advances in non Hodgkin lymphoma (NHL) survival. This study investigates several individual-level markers of socioeconomic position (SEP) in relation to NHL survival, and explores whether any social differences could be attributed to comorbidity, disease and prognostic factors, or the treatment given. METHODS: This registry-based cohort study links clinical data on prognostic factors and treatment from the national Danish lymphoma database to individual socioeconomic information in Statistics Denmark including 6234 patients diagnosed with NHL in 2000-2008. RESULTS: All cause mortality was 40% higher in NHL patients with short vs higher education diagnosed in the period 2000-2004 (hazard ratio (HR)=1.40 (1.27-1.54)), and 63% higher in the period 2005-2008 (HR=1.63 (1.40-1.90)). Further, mortality was increased in unemployed and disability pensioners, those with low income, and singles. Clinical prognostic factors attenuated, but did not eliminate the association between education and mortality. Radiotherapy was less frequently given to those with a short education (odds ratio (OR)= 0.84 (0.77-0.92)), low income (OR=0.80 (0.70-0.91)), and less frequent to singles (OR=0.79 (0.64-0.96)). Patients living alone were less likely to receive all treatment modalities. CONCLUSION: Patients with low SEP have an elevated mortality rate after a NHL diagnosis, and more advanced disease at the time of diagnosis explained a part of this disparity. Thus, socioeconomic disparities in NHL survival might be reduced by improving early detection among patients of low SEP. PMID- 22315056 TI - Circulating sphingosine-1-phosphate and erythrocyte sphingosine kinase-1 activity as novel biomarkers for early prostate cancer detection. AB - BACKGROUND: Current markers available for screening normal populations and for monitoring prostate cancer (PCa) treatment lack sensitivity and selectivity. Sphingosine-1-phosphate (S1P) is a circulating lipid second messenger involved in cell growth and migration, the immune response, angiogenesis, and malignant transformation. METHODS: Eighty-eight patients with localised, locally advanced, or metastatic PCa were recruited into this prospective single-centre study. Plasma S1P levels were measured and compared with age-matched controls with benign prostate hyperplasia (BPH) (n=110) or with young healthy males with the very small chance of having PCa foci (n=20). RESULTS: Levels of circulating S1P were significantly higher in healthy subjects (10.36 +/- 0.69 pmol per mg protein, P<0.0001) and patients with BPH (9.39 +/- 0.75, P=0.0013) than in patients with PCa (6.89 +/- 0.58, ANOVA, P=0.0019). Circulating S1P levels were an early marker of PCa progression to hormonal unresponsiveness and correlated with prostate-specific antigen (PSA) levels and lymph node metastasis. During the course of the study, nine patients have died of PCa. Importantly, their circulating S1P levels were significantly lower (5.11 +/- 0.75) than in the surviving patients (7.02 +/- 0.22, n=79, P=0.0439). Our data suggest that the decrease in circulating S1P during PCa progression may stem from a highly significant downregulation of erythrocyte sphingosine kinase-1 (SphK1) activity (2.14 +/- 0.17 pmol per mg protein per minute in PCa patients vs 4.7 +/- 0.42 in healthy individuals, P<0.0001), which may be a potential mechanism of cancer induced anaemia. CONCLUSION: This current study has provided a potential mechanism for cancer-related anaemia and the first evidence that plasma S1P and erythrocyte SphK1 activity are the potential markers for the diagnosis, monitoring, and predicating for PCa mortality. PMID- 22315057 TI - A phase 1 trial of recombinant human IL-21 in combination with cetuximab in patients with metastatic colorectal cancer. AB - BACKGROUND: Pre-clinical data indicate enhanced anti-tumour activity when combining recombinant human interleukin-21 (rIL-21), a class 1 cytokine, with cetuximab, a monoclonal antibody, targeting the epidermal growth factor receptor. This phase 1 trial assessed the safety and tolerability of escalating doses of rIL-21 in combination with cetuximab in chemo-naive patients with stage IV colorectal cancer. PATIENTS AND METHODS: Sequential cohorts of PS 0-1, asymptomatic patients, were treated weekly with cetuximab 250 mg m(-2) intravenously (i.v.) plus escalating i.v. doses of rIL-21 following an initial loading dose of cetuximab 400 mg m(-2). Initial treatment period was 8 weeks, with extension permitted in patients without disease progression. RESULTS: In all, 15 patients were included in this study. Adverse events related to rIL-21 or rIL-21 plus cetuximab included lethargy, nausea/vomiting, stomatitis, lymphopenia and pyrexia and were mainly <= grade 2. One dose limiting toxicity occurred (grade 3 diarrhoea). Maximum tolerated dose was not determined because of the premature study closure. Maximum administered dose was 100 MUg kg(-1) rIL-21 weekly. In all, 60% of the patients had stable disease. Immune activation was confirmed by various T- and NK-cell activation biomarkers, including dose dependent increases in serum sCD25. CONCLUSION: rIL-21 weekly combined with cetuximab is well tolerated at doses up to 100 MUg kg(-1) and results in activation of immune response biomarkers. PMID- 22315058 TI - Acquisition of EMT phenotype in the gefitinib-resistant cells of a head and neck squamous cell carcinoma cell line through Akt/GSK-3beta/snail signalling pathway. AB - BACKGROUND: Epithelial mesenchymal transition (EMT) is known to be associated with chemoresistance as well as increased invasion/metastasis. However, the relationship between EMT and resistance to an epidermal growth factor receptor (EGFR) -targeting drug in head and neck squamous cell carcinoma (HNSCC) remains unknown. In this study, we investigated the acquisition of EMT by gefitinib in HNSCC cell line (UMSCC81B). METHODS: We isolated fibroblastoid variant (81B-Fb) from gefitinib-resistant UMSCC81B-GR3 cells obtained after increasing the doses of gefitinib treatment in vitro and examined EMT and its underlying mechanism. RESULT: 81B-Fb cells exhibited fibroblast-like morphology, increased motility, loss of E-cadherin, acquisition of vimentin and snail expression. In 81B-Fb cells, downregulation of EGFR, which is mediated by increased ubiquitination, and activation of downstream protein kinase B (Akt), glycogen synthase kinase-beta (GSK-3beta) signalling and upregulation of snail expression were observed compared with UMSCC81B cells. LY294002, but not U0126, suppressed foetal bovine serum or heregulin-beta1-induced phosphorylation of Akt/GSK-3beta and snail expression together with the inhibition of 81B-Fb cell motility. Furthermore, forced expression of EGFR resulted in partial restoration of gefitinib sensitivity and reversal of EMT. CONCLUSION: These results suggest that EMT in the gefitinib-resistant cells is mediated by the downregulation of EGFR and compensatory activation of Akt/GSK-3beta/snail pathway. PMID- 22315059 TI - Ribozymes, catalytically active RNA molecules. Introduction. AB - It is now about 30 years since ribozymes, catalytically active RNA molecules, were discovered. Although the chemical versatility of RNA does not come close to that of proteins, the chemical properties of nucleic acid systems are nevertheless thoroughly exploited in biological systems, leading to diverse ways of accelerating chemical reactions. Ribozymes are truly fascinating biological molecules. After all, is catalytic RNA an accident of life or, instead, is life an accident of catalytic RNA? PMID- 22315060 TI - Characterization of hammerhead ribozyme reactions. AB - Hammerhead ribozymes are small catalytic RNA motifs ubiquitously present in a large variety of genomes. The reactions catalyzed by these motifs are both their self-scission and the reverse ligation reaction. Here, we describe methods for the generation of DNA templates for the subsequent in vitro transcription of hammerhead ribozymes. This is followed by a description of the preparation of suitable RNA molecules for both reaction types, and their kinetic analysis. PMID- 22315061 TI - Mechanistic analysis of the hepatitis delta virus (HDV) ribozyme: methods for RNA preparation, structure mapping, solvent isotope effects, and co-transcriptional cleavage. AB - Small ribozymes such as the hairpin, hammerhead, VS, glm S, and hepatitis delta virus (HDV) are self-cleaving RNAs that are typically characterized by kinetics and structural methods. Working with these RNAs requires attention to numerous experimental details. In this chapter we focus on four different experimental aspects of ribozyme studies: preparing the RNA, mapping its structure with reverse transcription and end-labeled techniques, solvent isotope experiments, and co-transcriptional cleavage assays. Although the focus of these methods is the HDV ribozyme, the methods should be applicable to other ribozymes. PMID- 22315062 TI - Kinetic characterization of hairpin ribozyme variants. AB - Kinetic analysis of ribozyme reactions is a common method to evaluate and compare activities of catalytic RNAs. The hairpin ribozyme catalyzes the reversible cleavage of a suitable RNA substrate at a specific site. Hairpin ribozyme variants as an allosteric ribozyme responsive to flavine mononucleotide and a hairpin-derived twin ribozyme that catalyzes two cleavage reactions and two ligation events with the result of a fragment exchange have been developed by rational design and were kinetically characterized. Herein, protocols for preparation of ribozymes and dye-labeled substrates as well as for analysis of cleavage, ligation, and fragment exchange reactions are provided. PMID- 22315063 TI - Characterization of RNase P RNA activity. AB - The principle task of the ubiquitous enzyme RNase P is the generation of mature tRNA 5'-ends by removing precursor sequences from tRNA primary transcripts (Trends Genet 19:561-569, 2003; Crit Rev Biochem Mol Biol 41:77-102, 2006; Trends Biochem Sci 31:333-341, 2006). In Bacteria, RNase P is a ribonucleoprotein composed of two essential subunits: a catalytic RNA subunit (P RNA; 350-400 nt) and a single small protein cofactor (P protein; ~14 kDa). In vitro, bacterial P RNA can catalyze tRNA maturation in the absence of the protein cofactor at elevated concentrations of mono- and divalent cations (Cell 35:849-857, 1983). Thus, bacterial P RNA is a trans-acting multiple-turnover ribozyme.Here we provide protocols for 5'-endonucleolytic ptRNA cleavage by bacterial P RNAs in the absence of any protein cofactor and under single-turnover conditions ([E] >> [S]). Furthermore, we outline a concept that utilizes the bacterial RNase P ribozyme to release RNAs of interest with homogeneous 3'-OH ends from primary transcripts via site-specific cleavage. Also, T7 transcription of mature tRNAs with clustered G residues at the 5'-end may result in 5'-end heterogeneities, which can be avoided by first transcribing the 5'-precursor tRNA (ptRNA) followed by P RNA-catalyzed processing to release the mature tRNA carrying a homogeneous 5'-monophosphate end. Finally, RNase P ribozyme activity can be directly assayed by using total bacterial RNA extracts. PMID- 22315064 TI - Group I intron ribozymes. AB - Group I intron ribozymes constitute one of the main classes of ribozymes and have been a particularly important model in the discovery of key concepts in RNA biology as well as in the development of new methods. Compared to other ribozyme classes, group I intron ribozymes display considerable variation both in their structure and the reactions they catalyze. The best described pathway is the splicing pathway that results in a spliced out intron and ligated exons. This is paralleled by the circularization pathway that leads to full-length circular intron and un-ligated exons. In addition, the intronic products of these pathways have the potential to integrate into targets and to form various types of circular RNA molecules. Thus, group I intron ribozymes and associated elements found within group I introns is a rich source of biological phenomena. This chapter provides a strategy and protocols for initial characterization of new group I intron ribozymes. PMID- 22315065 TI - Kinetic characterization of group II intron folding and splicing. AB - Group II introns are large self-splicing ribozymes found in bacterial genomes, in organelles of plants and fungi, and even in some animal organisms. Many organellar group II introns interrupt important housekeeping genes; therefore, their splicing is critical for the survival of the host organism. Group II introns are versatile catalytic RNAs: they facilitate their own excision from a pre-mRNA, they promote ligation of exons to form a translation-competent mature mRNA; they can act like mobile genomic elements and insert themselves into RNA and DNA targets with remarkable precision, which makes them attractive tools for genetic engineering. The first step in characterization of any group II intron is the evaluation of its catalytic activity and its ability to properly fold into the native functionally active structure. This chapter describes kinetic assays used to characterize folding and catalytic properties of group II intron-derived ribozymes. PMID- 22315066 TI - Mechanism and distribution of glmS ribozymes. AB - Among the nine classes of ribozymes that have been experimentally validated to date is the metabolite-responsive self-cleaving ribozyme called glmS. This RNA is almost exclusively located in the 5'-untranslated region of bacterial mRNAs that code for the production of GlmS proteins, which catalyze the synthesis of the aminosugar glucosamine-6-phosphate (GlcN6P). Each glmS ribozyme forms a conserved catalytic core that selectively binds GlcN6P and uses this metabolite as a cofactor to promote ribozyme self-cleavage. Metabolite-induced self-cleavage results in down-regulation of glmS gene expression, and thus the ribozyme functions as a key riboswitch component to permit feedback regulation of GlcN6P levels. Representatives of glmS ribozymes also serve as excellent experimental models to elucidate how RNAs fold to recognize small molecule ligands and promote chemical transformations. PMID- 22315067 TI - Structure-based search and in vitro analysis of self-cleaving ribozymes. AB - Detecting functional RNAs is increasingly accomplished through structure-based searches for patterns of conserved secondary structure. With large amounts of new sequencing data becoming available, there is a greater demand for efficient methods of identifying new RNAs. Here we present a method of identifying self cleaving ribozymes and characterizing the in vitro activity. PMID- 22315068 TI - Discovery of RNA motifs using a computational pipeline that allows insertions in paired regions and filtering of candidate sequences. AB - The enormous impact of noncoding RNAs on biology and biotechnology has motivated the development of systematic approaches to their discovery and characterization. Here we present a methodology for reliable detection of genomic ribozymes that centers on pipelined structure-based searches, utilizing two versatile algorithms for structure prediction. RNArobo is a prototype structure-based search package that enables a single search to return all sequences matching a designated motif descriptor, taking into account the possibility of single nucleotide insertions within base-paired regions. These outputs are then filtered through a structure prediction algorithm based on free energy minimization in order to maximize the proportion of catalytically active RNA motifs. This pipeline provides a fast approach to uncovering new catalytic RNAs with known secondary structures and verifying their activity in vitro. PMID- 22315069 TI - Crystallographic analysis of small ribozymes and riboswitches. AB - Ribozymes and riboswitches are RNA motifs that accelerate biological reactions and regulate gene expression in response to metabolite recognition, respectively. These RNA molecules gain functionality via complex folding that cannot be predicted a priori, and thus requires high-resolution three-dimensional structure determination to locate key functional attributes. Herein, we present an overview of the methods used to determine small RNA structures with an emphasis on RNA preparation, crystallization, and structure refinement. We draw upon examples from our own research in the analysis of the leadzyme ribozyme, the hairpin ribozyme, a class I preQ(1) riboswitch, and variants of a larger class II preQ(1) riboswitch. The methods presented provide a guide for comparable investigations of noncoding RNA molecules including a 48-solution, "first choice" RNA crystal screen compiled from our prior successes with commercially available screens. PMID- 22315070 TI - Functional dynamics of RNA ribozymes studied by NMR spectroscopy. AB - Catalytic RNA motifs (ribozymes) are involved in various cellular processes. Although functional cleavage of the RNA phosphodiester backbone for self-cleaving ribozymes strongly differs with respect to sequence specificity, the structural context, and the underlying mechanism, these ribozyme motifs constitute evolved RNA molecules that carry out identical chemical functionality. Therefore, they represent ideal systems for detailed studies of the underlying structure-function relationship, illustrating the diversity of RNA's functional role in biology. Nuclear magnetic resonance (NMR) spectroscopic methods in solution allow investigation of structure and dynamics of functional RNA motifs at atomic resolution. In addition, characterization of RNA conformational transitions initiated either through addition of specific cofactors, as e.g. ions or small molecules, or by photo-chemical triggering of essential RNA functional groups provides insights into the reaction mechanism. Here, we discuss applications of static and time-resolved NMR spectroscopy connected with the design of suitable NMR probes that have been applied to characterize global and local RNA functional dynamics together with cleavage-induced conformational transitions of two RNA ribozyme motifs: a minimal hammerhead ribozyme and an adenine-dependent hairpin ribozyme. PMID- 22315071 TI - Deoxyribozyme-based, semisynthetic access to stable peptidyl-tRNAs exemplified by tRNAVal carrying a macrolide antibiotic resistance peptide. AB - We present a protocol for the reliable synthesis of non-hydrolyzable 3'-peptidyl tRNAs that contain all the respective genuine nucleoside modifications. The approach is exemplified by tRNA(Val)-3'-NH-VFLVM-NH(2) and relies on commercially available Escherichia coli tRNA(Val). This tRNA was cleaved site-specifically within the TPsiC loop using a 10-23 type DNA enzyme to obtain a 58 nt tRNA 5' fragment which contained the modifications. After cleavage of the 2',3' cyclophosphate moiety from the 5'-fragment, it was ligated to the 18 nt RNA pentapeptide conjugate which had been chemically synthesized. By this methodology, tRNA(Val)-3'-NH-VFLVM-NH(2) is accessible in efficient manner. Furthermore, we point out that the approach is applicable to other types of tRNA. PMID- 22315072 TI - Probing functions of the ribosomal peptidyl transferase center by nucleotide analog interference. AB - The ribosome is a huge ribonucleoprotein complex in charge of protein synthesis in every living cell. The catalytic center of this dynamic molecular machine is entirely built up of 23S ribosomal RNA and therefore the ribosome can be referred to as the largest natural ribozyme known so far. The in vitro reconstitution approach of large ribosomal subunits described herein allows nucleotide analog interference studies to be performed. The approach is based on the site-specific introduction of nonnatural nucleotide analogs into the peptidyl transferase center, the active site located on the interface side of the large ribosomal subunit. This method combined with standard tests of ribosomal functions broadens the biochemical repertoire to investigate the mechanism of diverse aspects of translation considerably and adds another layer of molecular information on top of structural and mutational studies of the ribosome. PMID- 22315073 TI - Single molecule FRET characterization of large ribozyme folding. AB - A procedure to investigate the folding of group II intron by single molecule Fluorescence Resonance Energy Transfer (smFRET) using total internal reflection fluorescence microscopy (TIRFM) is described in this chapter. Using our previous studies on the folding and dynamics of a large ribozyme in the presence of metal ions (i.e., Mg(2+) and Ca(2+)) and/or the DEAD-box protein Mss116 as an example, we here describe step-by-step procedures to perform experiments. smFRET allows the investigation of individual molecules, thus, providing kinetic and mechanistic information hidden in ensemble averaged experiments. PMID- 22315074 TI - Metal ion-RNA interactions studied via multinuclear NMR. AB - Metal ions are indispensable for ribonucleic acids (RNAs) folding and activity. First they act as charge neutralization agents, allowing the RNA molecule to attain the complex active three dimensional structure. Second, metal ions are eventually directly involved in function. Nuclear magnetic resonance (NMR) spectroscopy offers several ways to study the RNA-metal ion interactions at an atomic level. Here, we first focus on special requirements for NMR sample preparation for this kind of experiments: the practical aspects of in vitro transcription and purification of small (<50 nt) RNA fragments are described, as well as the precautions that must be taken into account when a sample for metal ion titration experiments is prepared. Subsequently, we discuss the NMR techniques to accurately locate and characterize metal ion binding sites in a large RNA. For example, (2) J-[(1)H,(15)N]-HSQC (heteronuclear single quantum coherence) experiments are described to qualitatively distinguish between different modes of interaction. Finally, part of the last section is devoted to data analysis; this is how to calculate intrinsic affinity constants. PMID- 22315075 TI - Analysis of catalytic RNA structure and function by nucleotide analog interference mapping. AB - Nucleotide analog interference mapping (NAIM) is a quick and efficient method to define concurrently, yet singly, the importance of specific functional groups at particular nucleotide residues to the structure and function of an RNA. NAIM can be utilized on virtually any RNA with an assayable function. The method hinges on the ability to successfully incorporate, within an RNA transcript, various 5'-O (1-thio)nucleoside analogs randomly via in vitro transcription. This could be achieved by using wild-type or Y639F mutant T7 RNA polymerase, thereby creating a pool of analog doped RNAs. The pool when subjected to a selection step to separate the active transcripts from the inactive ones leads to the identification of functional groups that are crucial for RNA activity. The technique can be used to study ribozyme structure and function via monitoring of cleavage or ligation reactions, define functional groups critical for RNA folding, RNA-RNA interactions, and RNA interactions with proteins, metals, or other small molecules. All major classes of catalytic RNAs have been probed by NAIM. This is a generalized approach that should provide the scientific community with the tools to better understand RNA structure-activity relationships. PMID- 22315077 TI - Selecting allosteric ribozymes. AB - Allosteric ribozymes can be designed to respond to virtually any molecule of choice. The resulting species may be used for example as synthetic regulators of gene expression or alternatively as biosensors. In vitro selection techniques allow the isolation of active molecules from libraries as large as 10(15) different molecules. The present protocol describes an in vitro selection strategy for the de novo selection of allosteric self-cleaving ribozymes responding to virtually any drug of choice. We applied this method to select hammerhead ribozymes inhibited specifically by doxycycline or pefloxacin in the sub-micromolar range. The selected ribozymes can be converted into classical aptamers via insertion of a point mutation in the catalytic center of the ribozyme. PMID- 22315076 TI - In vitro selection of metal ion-selective DNAzymes. AB - The discovery of DNAzymes that can catalyze a wide range of reactions in the presence of metal ions is important on both fundamental and practical levels; it advances our understanding of metal-nucleic acid interactions and allows for the design of highly sensitive and selective metal ion sensors. A crucial factor in this success is a technique known as in vitro selection, which can rapidly select metal-specific RNA-cleaving DNAzymes. In vitro selection is an iterative process where a DNA pool containing a random region is incubated with the target metal ion. Those DNA sequences that catalyze the preferred reaction (the "winners") are amplified and carried on to the next step, where the selection is carried out under more stringent conditions. In this way, the selection pool becomes enriched with DNAzymes that exhibit desirable activity and selectivity. The method described can be applied to isolate DNAzymes selective to many different types of metal ions or different oxidation states of the same metal ion. PMID- 22315078 TI - Screening effective target sites on mRNA: a ribozyme library approach. AB - Hammerhead ribozymes have been extensively used as RNA-inactivating agents for therapy as well as forward genomics. A ribozyme can be designed so as to specifically pair with virtually any target RNA, and cleave the phosphodiester backbone at a specified location, thereby functionally inactivating the RNA. Two major factors that determine whether ribozymes will be effective for posttranscriptional gene silencing are colocalization of the ribozyme and the target RNAs, and the choice of an appropriate target site on the mRNA. Complex secondary structures and the ability to bind to some of the cellular proteins mandate that some RNA sequences could stearically occlude binding of RNA-based antivirals like ribozymes to these sites. The use of ribozyme libraries in cell culture factors in these interactions to select for target sites on the RNA, which are more accessible to RNA-based antivirals like ribozymes or siRNA. This chapter provides a useful guide toward using ribozyme libraries to screen for effective target sites on mRNA. PMID- 22315079 TI - A computational approach to predict suitable target sites for trans-acting minimal hammerhead ribozymes. AB - Trans-acting hammerhead ribozymes are challenging tools for diagnostic, therapeutic, and biosensoristic purposes, owing to their specificity, efficiency, and great flexibility of use. One of the main problems in their application is related to the difficulties in the design of active molecules and identification of suitable target sites.The aim of this chapter is to describe ALADDIN, "SeArch computing tooL for hAmmerheaD ribozyme DesIgN," an open-access tool able to automatically identify suitable cleavage sites and provide a set of hammerhead ribozymes putatively active against the selected target.ALADDIN is a fast, cheap, helpful, and accurate tool designed to overcome the problems in the design of trans-acting minimal hammerhead ribozymes. PMID- 22315080 TI - Targeting mRNAs by engineered sequence-specific RNase P ribozymes. AB - The methods of using engineered RNase P catalytic RNA (termed as M1GS RNA) for in vitro and in vivo in trans-cleavage of target viral mRNA are described in this chapter. Detailed information is focused on (1) mapping accessible regions of target viral mRNA in infected cells, (2) generation and in vitro cleavage assay of the customized M1GS ribozyme, (3) stable expression of M1GS RNAs and evaluation of its antiviral activity in cultured cells. Using these methods, we have constructed functional M1GS ribozyme that can cleave an overlapping region of the mRNAs coding for the human cytomegalovirus (HCMV) capsid scaffolding protein (CSP) and assemblin in vitro. Further study has demonstrated that, in cultured human cells expressing the functional M1GS ribozyme and infected with HCMV, more than 85% reduction in the expression of CSP and assemblin and a 4,000 fold reduction in viral growth were achieved. Our study provided the direct evidence that the customized M1GS ribozyme can be used as an effective gene targeting agent for in trans-cleavage of viral genes and inhibition of viral growth in cultured cells. PMID- 22315081 TI - Target-induced SOFA-HDV ribozyme. AB - Small cis-acting ribozymes have been converted into trans-acting ribozymes possessing the ability to cleave RNA substrates. The Hepatitis Delta Virus (HDV) ribozyme is one of the rare examples of these that is derived from an RNA species that is found in human cells. Consequently, it possesses the natural ability to function in the presence of human proteins in addition to an outstanding stability in human cells, two significant advantages in its use. The development of an additional specific on/off adaptor (SOFA) has led to the production of a new generation of HDV ribozymes with improved specificities that provide a tool with significant potential for future development in the fields of both functional genomics and gene -therapy. SOFA-HDV ribozyme-based gene inactivation systems have been reported in both prokaryotic and eukaryotic cells. Here, a step by-step approach for the efficient design of highly specific SOFA-HDV ribozymes with a minimum investment of time and effort is described. PMID- 22315082 TI - Ribozyme-mediated trans insertion-splicing into target RNAs. AB - The trans insertion-splicing (TIS) reaction is a technique that can be used to site-specifically insert an RNA donor substrate into a separate RNA acceptor substrate. The TIS reaction, which is catalyzed by a group I intron-derived ribozyme from Pneumocystis carinii, is described with regards to system design, ribozyme preparation, and the overall protocol for conducting the TIS reaction. PMID- 22315083 TI - Developing fluorogenic RNA-cleaving DNAzymes for biosensing applications. AB - Deoxyribozymes (or DNAzymes) are single-stranded DNA molecules that have the ability to catalyze a chemical reaction. Currently, DNAzymes have to be isolated from random-sequence DNA libraries by a process known as in vitro selection (IVS) because no naturally occurring DNAzyme has been discovered. Several IVS studies have led to the isolation of many RNA-cleaving DNAzymes (RNase DNAzymes), which catalyze the transesterification of a phosphodiester linkage in an RNA substrate, resulting in its cleavage. An RNase DNAzyme and its substrate can be modified with a pair of donor and acceptor fluorophores (or a fluorophore and quencher pair) to create a fluorescence-signaling system (a signaling DNAzyme) where the RNA-cleaving activity of the DNAzyme is reported through the generation of a fluorescent signal. A signaling DNAzyme can be further coupled with an aptamer (a target-binding nucleic acid sequence) to generate a fluorogenic aptazyme in which the aptamer-target interaction confers an allosteric control of the coupled RNA cleaving and fluorescence-signaling activity of the DNAzyme. Fluorogenic aptazymes can be exploited as valuable molecular tools for biosensing applications. In this chapter, we provide both a detailed description of methods for isolation of signaling DNAzymes by IVS and general approaches for rational engineering of fluorogenic aptazymes for target detection. PMID- 22315084 TI - Development of trainable deoxyribozyme-based game playing automaton. AB - Molecular automata are self-operating machines serially exchanging information with their environment while changing their configurations. Molecular protoautomata are devices trained in a series of sessions with an operator to become molecular automata. Reconfigurable deoxyribozyme-based logic gates can be used to build multipurpose protoautomata, reprogrammable devices that go beyond single-purpose "hard-wired" molecular automata. Molecular array of YES and AND gates (MAYA)-III is such a protoautomaton that can be taught by example to play a game. Training of MAYA-III is a process that does not require the operator to be familiar with the underlying molecular programming. Herein we provide the instructions to construct this protoautomaton, with particular focus on the optimization of computing components. PMID- 22315085 TI - Rational design and tuning of ribozyme-based devices. AB - A synthetic gene-regulatory device platform was described by modularly assembling three RNA components encoding distinct functions of sensing, transmission, and actuation. The molecular binding at the sensor component is translated by the transmitter component through a strand-displacement event to modulate activity of the actuator component, which then interacts with cellular transcriptional machinery to affect gene expression levels. Here, we provide some general guidelines on linking RNA components to construct gene-regulatory devices and strategies to tune device regulatory activities through an RNA folding -program for specific cellular applications. PMID- 22315086 TI - In vivo screening of ligand-dependent hammerhead ribozymes. AB - The development of artificial switches of gene expression is of high importance for future applications in biotechnology and synthetic biology. We have developed a powerful RNA-based system which allows for the ligand-dependent and reprogrammable control of gene expression in Escherichia coli. Our system makes use of the hammerhead ribozyme (HHR) which acts as molecular scaffold for the sequestration of the ribosome binding site (RBS), mimicking expression platforms in naturally occurring riboswitches. Aptamer domains can be attached to the ribozyme as exchangeable ligand-sensing modules. Addition of ligands to the bacterial growth medium changes the activity of the ligand-dependent self cleaving ribozyme which in turn switches gene expression. In this chapter, we describe the in vivo screening procedure allowing for reprogramming the ligand specificity of our system. PMID- 22315087 TI - Flexizymes as a tRNA acylation tool facilitating genetic code reprogramming. AB - Genetic code reprogramming is a method for the reassignment of arbitrary codons from proteinogenic amino acids to non-proteinogenic ones, and thus specific sequences of nonstandard peptides can be ribosomally expressed according to their mRNA templates. We here describe a protocol that facilitates the genetic code reprogramming using flexizymes integrated with a custom-made in vitro translation apparatus, referred to as the flexible in vitro translation (FIT) system. Flexizymes are flexible tRNA acylation ribozymes that enable the preparation of a diverse array of non-proteinogenic acyl-tRNAs. These acyl-tRNAs read vacant codons created in the FIT system, yielding the desired nonstandard peptides with diverse exotic structures, such as N-acyl groups, D: -amino acids, N-methyl amino acids, and physiologically stable macrocyclic scaffolds. Facility of the protocol allows for a wide variety of applications in the synthesis of new classes of nonstandard peptides with biological functions. PMID- 22315088 TI - Polymerase chain reaction assay for rapid, sensitive detection, and identification of Colletotrichum gloeosporioides causing greater yam anthracnose. AB - Anthracnose caused by Colletotrichum gloeosporioides is an economically important disease which affects greater yam (Dioscorea alata L.) worldwide. Apart from airborne conidia, the pathogen propagules surviving in soil and planting material are the major sources of inoculum. A nested PCR assay has been developed for specific detection of C. gloeosporioides in soil and planting material. In conventional (single-round) PCR, the limit of detection was 20 pg, whereas in nested PCR the detection limit increased to 0.2 pg of DNA. The primers designed were found to be highly specific and could be used for accurate identification of the pathogen up to species level. The protocol was standardized for detection of the pathogen in artificially and naturally infected field samples. PMID- 22315089 TI - Three years prospective investigation of pituitary functions following subarachnoid haemorrhage. AB - Subarachnoid haemorrhage (SAH) is known to be related to pituitary dysfuntion in retrospective and short-term prospective studies. We aimed to investigate pituitary functions in patients with SAH in longer follow-up periods to demonstrate if pituitary hormone deficiencies recover, persist or new hormone deficiencies occur. Twenty patients with SAH, who were followed up for 3 years, were included in the present study. Patients were evaluated with basal hormone levels and glucagon stimulation test (GST).Serum basal cortisol and adrenocorticotropic hormone (ACTH) levels were found to be significantly elevated at 3rd year of SAH compared to 1st year. Other basal hormone levels at 3rd year did not show a significant change from the levels found at 1st year. One of the patients had ACTH deficiency at 1st year of SAH and recovered at 3rd year. Growth hormone (GH) deficiency, according to GST,was diagnosed in 4 patients. One patient with GH deficiency at first year was still deficient, 3 of them recovered and 3 patients were found to have new-onset GH deficiency 3 years after SAH. SAH is associated with anterior pituitary dysfunction and GH is the most frequently found deficient hormone in the patients. Although one year after SAH seems to be an appropriate time for the evaluation of pituitary functions, further follow-up may be required at least in some cases due to recovered and new-onset hormone deficiencies at 3rd year of SAH. PMID- 22315090 TI - Silencing of tumor suppressor genes RASSF1A, SLIT2, and WIF1 by promoter hypermethylation in hereditary breast cancer. AB - Promoter hypermethylation is gaining strength as one of the main mechanisms through which tumor suppressor genes are silenced during tumor progression. Three tumor suppressor genes are frequently found methylated in their promoter, in concordance with absence of expression, RASSF1A, SLIT2, and WIF1. In addition, a previous array-CGH analysis from our group showed that these genes are found in deleted genomic regions observed in hereditary breast cancer tumors. In the present work we analyzed the methylation status of these three tumor suppressor gene promoters in 47 hereditary breast cancer tumors. Promoter methylation status analysis of hereditary breast tumors revealed high methylation frequencies for the three genes (67% RASSF1A, 80% SLIT2, and 72% WIF1). Additionally, the presence of methylated PCR products was associated with absence of protein expression for the three genes and statistically significant for RASSF1A and WIF1. Interestingly, methylation of all the three genes was found in 4 out of 6 grade I invasive ductal carcinoma tumors. Association between RASSF1A methylation and DCIS tumors was found. These results suggest that silencing of these tumor suppressor genes is an early event in hereditary breast cancer, and could be a marker for pre-malignant phenotypes. PMID- 22315091 TI - Influence of sildenafil on the anticonvulsant action of selected antiepileptic drugs against pentylenetetrazole-induced clonic seizures in mice. AB - The aim of the present study was to investigate the effect of sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, on threshold for clonic seizures in mice. In addition, the effects of sildenafil on the anticonvulsant activity of selected antiepileptic drugs (AEDs), i.e., clonazepam (CZP), valproate (VPA), phenobarbital (PB), ethosuximide (ETS) and tiagabine (TGB), were also evaluated. The subcutaneous pentylenetetrazole (PTZ) test was used to determine the effects of sildenafil on convulsive susceptibility and the anticonvulsant activity of the studied AEDs in mice, while the acute side effects of sildenafil and its combinations with the studied AEDs were evaluated in the chimney test, step through passive-avoidance task and grip-strength test in mice. Total brain concentrations of AEDs were also determined. Sildenafil (5-40 mg/kg) did not influence the threshold for PTZ-induced clonic seizures in mice, but increased the anticonvulsant activity of ETS in this test without any significant changes in the total brain concentration. The activity of the remaining AEDs was not significantly changed by sildenafil. Neither sildenafil alone nor its combinations with the studied AEDs produced any changes in the motor coordination, long-term memory and muscular strength in mice. Co-administration of sildenafil with ETS in male epileptic patients with co-existing erectile dysfunctions might lead to the pharmacodynamic interactions that may be beneficial for the patients. Combinations of sildenafil with CZP, VPA, PB and TGB appear to be neutral in terms of their influence on seizures. PMID- 22315092 TI - Shotgun proteomics and network analysis of neuroblastoma cell lines treated with curcumin. AB - Curcumin is a natural compound with recognized anti-inflammatory properties, but its anticancer activity is still object of study. We provided an unsupervised molecular investigation of the main proteome rearrangements involved in the cellular response to curcumin in a human neuroblastoma cell line sensitive to cisplatin and its resistant counterpart by a comparative proteomic approach. Shotgun analysis demonstrated that 66 proteins were differentially expressed in response to 24 h treatment with 40 MUM curcumin in sensitive cells, whereas 32 proteins were significantly modulated in treated resistant cells. Functional analysis revealed that proteins involved in cellular assembly and organization, biosynthesis and glycolysis were down-regulated by curcumin treatment. Proteome changes were associated to cell cycle arrest in the G2/M phase and accumulation of polyubiquitinated proteins, also confirmed by flow cytometry and immunoblotting analysis, but not to a significant increment of reactive oxygen species production. Since the polyubiquitination of proteins influences a wide range of cellular pathways, the inhibition of the ubiquitin-proteasome system may be the main way through which curcumin performs its multi-target activity. PMID- 22315093 TI - Role of adjuvant hysterectomy in management of high-risk gestational trophoblastic neoplasia. AB - OBJECTIVES: The objectives of the study were to investigate the role of and indications for adjuvant hysterectomy in patients with high-risk gestational trophoblastic neoplasia. METHODS: We retrospectively analyzed records of patients identified as having undergone adjuvant hysterectomy for high-risk gestational trophoblastic neoplasia at First Hospital of Xi'an Jiaotong University, Xi'an, China, between 1985 and 2005. Therapeutic response was defined as complete with normalization of human chorionic gonadotropin (hCG) concentration, partial response with a decrease of more than 50%, and no response with a decrease of 50% or less. Complete remission was defined as normal hCG at 3 consecutive weekly assays without clinical evidence of disease. RESULTS: A total of 21 patients (72.4%) showed an initial therapeutic response after surgery and 8 (27.6%) had no response. The initial therapeutic response was complete in 8 patients (27.6%) and partial in 13 (44.8%). During follow-up of 6 to 168 months, all 21 patients with an initial response and 2 of 8 patients without an initial response ultimately achieved complete remission (23 of 29 patients, 79.3%). Three patients (10.3%) had recurrence after primary remission; 2 patients (6.90%) died. Metastases outside of lungs or pelvic organs, number of metastases, presurgery chemoresistance to multidrug regimens, especially with 2 or more failed protocols, were considered possible reasons for decreased effectiveness of hysterectomy. CONCLUSIONS: Our study suggests that timely adjuvant hysterectomy is likely to benefit cautiously selected patients with high-risk gestational trophoblastic neoplasia. Although preoperative metastases limited to pelvic organs or lungs should not be considered an absolute contraindication, adjuvant hysterectomy should generally not be performed in the presence of distant metastases beyond the pelvic organs and lungs. PMID- 22315094 TI - Microparticles from ovarian carcinomas are shed into ascites and promote cell migration. AB - OBJECTIVE: Microparticles are cellular-derived vesicles (0.5-1.0 MUm) composed of cell membrane components, which are actively shed from the surface of various cells, including epithelial cells. We compared microparticles in ascites between women with ovarian carcinoma and women with benign ovarian pathology, and isolated tumor-derived (epithelial cell adhesion molecule [EpCAM]-positive) microparticles for functional analysis and proteomics. MATERIALS AND METHODS: Cases included 8 patients with benign ovarian neoplasms and 41 with ovarian carcinoma. Ascites from a high-grade stage III serous carcinoma was used for functional and proteomic analysis. Cancer cells were isolated using EpCAM-coated beads, microparticles were isolated by ultracentrifugation/flow cytometry, and sorting was achieved using markers (eg, EpCAM). Binding and migrations assays were performed with 3 ovarian cancer cell lines. Proteomic analysis of EpCAM positive microparticles and ascites cancer cells was performed by mass spectrometry. RESULTS: Microparticles in benign pelvic fluid were similar to early and advanced-stage ascites (2.4 vs 2.8 vs 2.0 * 106 microparticles/mL). Advanced stage had a greater proportion of EpCAM-positive microparticles than early or benign disease (13.3% vs 2.5% vs 2.1%; P = 0.001), and serous histology had more than endometrioid (13.2% vs 1.8%; P = 0.01). Microparticles bound to the surface of 3 cultured cell lines, and were internalized into the EpCAM-positive microparticles, resulting in more cell migration than buffer alone or EpCAM negative microparticles (P = 0.007). A dose-dependent increase was seen with increasing numbers of EpCAM-positive microparticles. Proteomics revealed that most proteins in EPCAM-positive microparticles were shared with cancer cells, and many are associated with cell motility and invasion, such as fibronectin, filamin A, vimentin, myosin-9, and fibrinogen. CONCLUSIONS: Ascites from advanced-stage and serous ovarian carcinomas contain large numbers of tumor-derived microparticles. In vitro, these microparticles bind to cancer cells and stimulate migration. Tumor-derived microparticles in ascites could mediate the predilection for peritoneal spread in serous ovarian carcinomas. PMID- 22315095 TI - Percutaneous nephrostomy versus indwelling ureteral stent in the management of gynecological malignancies. AB - OBJECTIVES: The aims of this study were to evaluate the efficacy of retrograde ureteral stenting and to identify the predictive factors for potential failure of this technique in women with advanced gynecologic malignancies. METHODS: From 2006 to 2010, a retrospective analysis was performed on a total of 75 patients with ureteral obstruction due to gynecologic malignancies. This population was divided into group 1 (n = 50) in which retrograde stent placement was successful, and group 2 (n = 25) in which stent placement failed and subsequent percutaneous nephrostomy tube placement was required. Multivariate analysis was done to identify predictors of the failure of ureteral stent insertion. RESULTS: Multivariate analysis revealed that mean preprocedureal serum cystanin C greater than 2.5 mg/L and length of the ureteral obstruction greater than 3 cm were significant predictors of stent failure. Neither the causes nor location of obstruction predicted the need for percutaneous nephrostomy (PCN). No statistical significance was detected among the subgroups of patients with different degrees of hydronephrosis. Statistical significant differences were found between the 2 groups in procedural time, average cost, and mean interval of stent/catheter replacement. However, no statistically significant difference was found in the median survival time and overall stent-related or catheter-related complications between the 2 groups. CONCLUSIONS: Retrograde ureteral stenting is a first-line option for managing ureteral obstruction caused by gynecologic malignancies. However, in cases where the preprocedureal mean serum cystanin C is greater than 2.5 mg/L and the length of the ureteral obstruction segment is greater than 3 cm, these patients may be better served by percutaneous drainage. PMID- 22315096 TI - The role of polymorphisms at position 89 in the HIV-1 protease gene in the development of drug resistance to HIV-1 protease inhibitors. AB - OBJECTIVES: Relatively little is known about the development of resistance to protease inhibitors (PIs) in non-B subtypes. In subtype B viruses, L89 is commonly found at position 89 in the HIV protease (PR) gene, whereas M89 is commonly observed as a polymorphism in other subtypes. We compared the frequencies of substitutions at position 89 in PR in tissue culture selections and in clinical databases of PI-naive and PI-experienced populations. METHODS: Representative subtype A/CRF01_AE (n = 2 and 3) and subtype C (n = 5) isolates were cultured in MT-2 cells and cord blood mononuclear cells (CBMCs), respectively, under increasing drug pressure with PIs, and drug resistance mutations were identified. RESULTS: The M89 natural polymorphism in non-B subtypes commonly led to the appearance of an M89T mutation in selections with atazanavir in subtypes A/AE and C, and was accompanied by other previously recognized atazanavir mutations. The M89T mutation contributed to phenotypic resistance to atazanavir and cross-resistance to lopinavir and nelfinavir, but not to other PIs. A shift from a L89 natural polymorphism to L89I/M arose in two of five subtype C selections with PIs. M89I/V/T mutations were acquired by 10% 11% of individuals harbouring non-B subtypes who were failing PI-based regimens, but were rarely observed in drug-naive persons and in patients failing non-PI based regimens. CONCLUSIONS: The M/L89 natural polymorphism present in non-B subtypes may lead to the M89T mutational pathway conferring resistance to atazanavir, lopinavir and nelfinavir. PMID- 22315097 TI - Carbon source pulsed feeding to attain high yield and high productivity in poly(3 hydroxybutyrate) (PHB) production from soybean oil using Cupriavidus necator. AB - Poly(3-hydroxybutyrate) (PHB) biosynthesis from soybean oil by Cupriavidus necator was studied using a bench scale bioreactor. The highest cell concentration (83 g l(-1)) was achieved using soybean oil at 40 g l(-1) and a pulse of the same concentration. The PHB content was 81% (w/w), PHB productivity was 2.5 g l(-1) h(-1), and the calculated Y(p/s) value was 0.85 g g(-1). Growth limitation and the onset of PHB biosynthesis took place due to exhaustion of P, and probably also Cu, Ca, and Fe. PMID- 22315098 TI - Construction of an expression system for the secretory production of recombinant alpha-agarase in yeast. AB - alpha-Agarase hydrolyzes the alpha-1,3 linkage of agarose yielding agaro oligosaccharides. It is less well characterized than beta-agarase. AgaA gene (2.3 kb ORF), encoding the alpha-agarase from Thalassomonas JAMB A33, was subcloned into both a constitutive and an inducible expression vector. Both the constructed plasmids, pVT-AgaA (ADH1 promoter) and pYInu-AgaA (GAL10 promoter), were transformed into Saccharomyces cerevisiae SEY2102 and FY833 and pPIC9-AgaA harboring the AOX1 promoter was transformed into Pichia pastoris GS115. The recombinant alpha-agarases were over-expressed with activities from 0.3 to 1.6 unit/ml, the highest being in the SEY2102/pYInu-AgaA transformant. Most of the recombinant alpha-agarase was extracellular because each plasmid possesses a signal sequence for the secretory production of alpha-agarase. In contrast, the Pichia host-vector expression system was unsuitable for the production of recombinant alpha-agarase. This is the first report of recombinant production of alpha-agarase in yeast for industrial use. PMID- 22315099 TI - Maintenance of membrane integrity and increase of taxanes production in hazel (Corylus avellana L.) cells induced by low-intensity ultrasound. AB - Suspension-cultured hazel cells were ultrasonicated at power densities of 4 and 455 mW for 4-40 min. Both treatments stimulated the production of major taxanes: Taxol, 10-deacetylbaccatin, and baccatin III. The highest amounts of these taxanes (0.46, 0.26, and 0.07 mg/l, respectively) were obtained at 8 and 20 min of the treatment at 455 mW. Ultrasound had no adverse effects on cell viability, growth, or membrane integrity. Increased release of taxanes by ultrasound resulted not from increased membrane permeability but more likely from stimulation of taxanes biosynthesis. PMID- 22315100 TI - Purification and properties of an extracellular esterase from a cold-adapted Pseudomonas mandelii. AB - An extracellular esterase, EstK, was purified from the psychrotrophic bacterium Pseudomonas mandelii grown at 25 degrees C. Prior to harvest, cells were treated with 0.2 M MgCl2 to precipitate lipopolysaccharides in the outer membranes, which otherwise form aggregates with the secreted enzymes. EstK was purified to homogeneity using standard procedures. It had substrate specificity towards esters of short-chain fatty acids, particularly, p-nitrophenyl acetate. Optimum activity of EstK was at 40 degrees C; at 4 degrees C the activity was ~50% of its maximum. EstK has a unique substrate preference for p-nitrophenyl acetate and remains active at low temperatures. PMID- 22315101 TI - On-line measurement of the substrate concentrations in Pichia pastoris fermentations using FT-IR/ATR. AB - The glycerol and methanol concentrations in Pichia pastoris fermentations were measured on-line using Fourier transform infrared spectroscopy and an attenuated total reflection probe. Partial least squares regression was used to obtain calibration models. The models were regressed on synthetic multi-component spectra and semi-synthetic fermentation broth spectra. These were obtained by spectral addition. The accuracy for the on-line measurement of glycerol, given as standard error of prediction (SEP), was determined to 0.68 g/l, and the SEP of methanol was 0.13 g/l. We show how reliable calibration models are obtained relatively effortlessly by replacing extensive sampling from the reactor with simple mathematical manipulations of the model regression spectra. PMID- 22315103 TI - [Pitfalls : A new rubric in Der Pathologe.] PMID- 22315102 TI - [Pathowiki. A free expert database for pathology]. AB - The project Pathowiki (www.pathowiki.org) is a free expert database for texts, images, virtual slides and links to all subject areas of pathology in the internet. The aim of this project is to integrate all available information and media, in particular virtual microscopy, to achieve a fast overview of a relevant subject area. Here we present the project's basic functions and applications and evaluate the project with respect to the ongoing digital developments in pathology. PMID- 22315104 TI - Combined time- and space-resolved Raman spectrometer for the non-invasive depth profiling of chemical hazards. AB - A time-resolved inverse spatially offset Raman spectrometer was constructed for depth profiling of Raman-active substances under both the lab and the field environments. The system operating principles and performance are discussed along with its advantages relative to traditional continuous wave spatially offset Raman spectrometer. The developed spectrometer uses a combination of space- and time-resolved detection in order to obtain high-quality Raman spectra from substances hidden behind coloured opaque surface layers, such as plastic and garments, with a single measurement. The time-gated spatially offset Raman spectrometer was successfully used to detect concealed explosives and drug precursors under incandescent and fluorescent background light as well as under daylight. The average screening time was 50 s per measurement. The excitation energy requirements were relatively low (20 mW) which makes the probe safe for screening hazardous substances. The unit has been designed with nanosecond laser excitation and gated detection, making it of lower cost and complexity than previous picosecond-based systems, to provide a functional platform for in-line or in-field sensing of chemical substances. PMID- 22315105 TI - Magnetic Fe3O4 nanoparticles coupled with a fluorescent Eu complex for dual imaging applications. AB - Magnetic 8 nm Fe(3)O(4) nanoparticles (NPs) were synthesized and modified with dopamine (DPA) and polyethylene glycol (PEG) diacid. The water soluble Fe(3)O(4) DPA-PEG NPs were then conjugated with the fluorescent Eu(iii) complex of tris(dibenzoylmethane)-5-amino-1,10-phenanthroline (BMAP), giving an Fe(3)O(4) DPA-PEG-BMAP-Eu NP conjugate. The conjugate was both colloidally and chemically stable in phosphate buffered solutions and could be used as a probe for magnetic resonance and fluorescent imaging. PMID- 22315106 TI - Decreased startle modulation during anticipation in the postpartum period in comparison to late pregnancy. AB - Knowledge about healthy women's psychophysiological adaptations during the large neuroendocrine changes of pregnancy and childbirth is essential in order to understand why these events have the potential to disrupt mental health in vulnerable individuals. This study aimed to compare startle response modulation, an objective psychophysiological measure demonstrated to be influenced by anxiety and depression, longitudinally across late pregnancy and the postpartum period. The acoustic startle response modulation was assessed during anticipation of affective images and during image viewing in 31 healthy women during gestational weeks 36-39 and again at 4 to 6 weeks postpartum. No startle modulation by affective images was observed at either time point. Significant modulation during anticipation stimuli was found at pregnancy assessment but was reduced in the postpartum period. The women rated the unpleasant images more negative and more arousing and the pleasant images more positive at the postpartum assessment. Self reported anxiety and depressive symptoms did not change between assessments. The observed postpartum decrease in modulation of startle by anticipation suggests a relatively deactivated defense system in the postpartum period. PMID- 22315107 TI - Metaconceptual Frameworks and the Study of Human Infant Category Construction. AB - Dellantonio, Innamoratia, & Pastore (2012) consider different interpretations of the notion of a boundary, comparing specifically the metaconceptual frameworks of exclusive and inclusive separation. I elaborate the target article by considering what a shift to the strategy of inclusive separation entails. Specifically, it is suggested that this shift introduces a greater focus on the process of development, as well as a consideration of the ambivalence and emergence involved in boundary processes. Poetry is used as an example to illustrate these qualities of these boundary processes. It is suggested that when reading a poem, within the boundary of the literal and imagined senses of words productive tensions are created, and often in overcoming those tensions the person can arrive at overgeneralized, affectively laden meanings which guide future thought, action and behavior. It is suggested that in everyday life, the cultural construction of feeling follows a similar process, taking on a poetic form. PMID- 22315108 TI - Introducing the future of ACCP Clinical Practice Guidelines. PMID- 22315109 TI - Asthma guidelines and smokers: it's time to be inclusive. PMID- 22315110 TI - Endobronchial ultrasound: hitting the trifecta or the perfect storm? PMID- 22315111 TI - Atrial fibrillation: it is better to be alone than in bad company! PMID- 22315112 TI - Prevention of embolic strokes: the role of the American College of Chest Physicians. AB - Patients with atrial fibrillation (AF) face an annual stroke risk of about 5%. Evidence that anticoagulants reduce the risk of stroke has evolved over the 20th century. The American College of Chest Physicians (ACCP) has played a critical role in presenting guidelines for stroke prevention in AF. This commentary highlights the role that the ACCP guidelines have played, from their inception to the ninth edition. The first ACCP Conference on Antithrombotic and Thrombolytic Therapy in 1986 developed evidence-based guidelines for the indications, dosage, and monitoring of antithrombotic therapy. The conference recommended that anticoagulants be monitored by the international normalized ratio, and the appropriate dosage was to increase the international normalized ratio to two to three times control. This recommendation was widely accepted. Anticoagulants were recommended for AF with mitral valve disease and for nonvalvular AF with a history of embolism. No recommendations were made for nonvalvular AF without a history of embolism. These recommendations stimulated numerous randomized controlled trials (RCTs). By the third ACCP conference in 1992, RCTs had demonstrated a dramatic 69% stroke reduction in patients with nonvalvular AF. The third ACCP conference was the first to strongly recommend anticoagulation for primary and secondary stroke prevention in nonvalvular AF. ACCP conferences since 1992 have refined recommendations for nonvalvular AF on the basis of associated risk factors. The most recent conference, in 2011, recommended a direct thrombin inhibitor, dabigatran, rather than warfarin as the anticoagulant of choice. These ACCP guidelines have played a critical role in changing physicians' practice patterns. In 1980 only 7% of patients with AF in the United States received OA; by 2007, this had increased to 57%. PMID- 22315113 TI - Will performance measurement lead to better patient outcomes? What are the roles of the National Quality Forum and Medical Specialty Societies? AB - Performance measures (PMs) are specified metrics by which a health-care provider's care can be compared with national benchmarks. The use of PMs is a key component of efforts to improve the quality and value of health care. The National Quality Forum (NQF) is the federally recognized endorser of PMs. From 2006 to 2009, the Quality Improvement Committee (QIC) of the American College of Chest Physicians engaged in the review of proposed PMs as a member of the NQF. This article provides a review of the QIC's experience with PMs and NQF membership and the lessons learned, an overview of the enhancements made to the NQF endorsement process in 2010 and 2011, and a discussion of the next steps that would further strengthen the measure development and endorsement processes and increase the likelihood of measurement leading to better patient outcomes. PMID- 22315114 TI - Pharmacologic and compression therapies for postthrombotic syndrome: a systematic review of randomized controlled trials. AB - BACKGROUND: Postthrombotic syndrome (PTS) is a frequent, chronic complication of DVT. The effectiveness and safety of available treatments are unknown. The objective of this study was to systematically review the literature to assess whether pharmacologic and compression therapies are effective and safe for the treatment of PTS. METHODS: We sought to identify randomized controlled trials (RCTs) via a search of PubMed, studies referenced in included publications, and studies that cited relevant literature. RESULTS: A total of 121 titles were reviewed, 12 full-text publications were assessed for inclusion, and seven RCTs, including 703 patients, were selected for inclusion. Four trials assessed the effectiveness of drugs, including rutosides, hidrosmin, and defibrotide, and four trials assessed compression therapies for treatment of PTS. Systems for the diagnosis and classification of PTS severity varied across studies. Three of four drug therapy trials reported moderate improvement in selected PTS symptoms, minor changes in calf and ankle circumference, and some effects on ulcer healing. Two studies of compression stockings did not report benefit. Two studies that assessed compression devices reported improvement in PTS symptoms scores; one of these reported an improvement in quality-of-life score. CONCLUSIONS: There is limited and low-quality evidence for the effectiveness of rutosides, hidrosmin, defibrotide, and compression stockings, but moderate-quality evidence that supports the use of intermittent compression to provide at least short-term relief from PTS. More rigorous studies are needed to assess the short- and long term effectiveness and safety of PTS therapies. PMID- 22315115 TI - OX40/OX40 ligand interactions in T-cell regulation and asthma. AB - The OX40 receptor is preferentially expressed by T cells, and its cognate ligand OX40L is primarily expressed by antigen-presenting cells such as dendritic cells following activation by thymic stromal lymphopoietin (TSLP). TSLP is released by the bronchial epithelium, airway smooth muscle, and some inflammatory cells in response to numerous insults such as allergens, viruses, and physical damage. OX40L is a costimulatory molecule that plays a sentinel role in the adaptive immune response by promoting T helper (Th) 2 polarization of naive T cells within the lymph node. These polarized T cells produce Th2 cytokines such as IL-4, IL-5, and IL-13, which have been implicated particularly in allergic eosinophilic asthma. Animal models have positioned both TSLP and OX40/OX40L as critical in the development of airway inflammation and hyperreactivity. In human disease, there is good evidence that TSLP is upregulated in asthma, but there are limited data to demonstrate overexpression of OX40 or OX40L in disease. Targeting the OX40/OX40L axis or TSLP presents a novel therapeutic strategy that has the potential of modifying the disease process and, therefore, impacting on its natural history. Whether this approach can demonstrate efficacy in established disease rather than at disease onset is unknown. Biologic therapies directed toward OX40/OX40L are in early phases of development, and results from these studies are eagerly awaited. PMID- 22315116 TI - Advancing cardiovascular research. AB - Over the past 50 years, we have seen dramatic changes in cardiovascular science and clinical care, accompanied by marked declines in the morbidity and mortality. Nonetheless, cardiovascular disease remains the leading cause of death and disability in the world, and its nature is changing as Americans become older, fatter, and ethnically more diverse. Instead of young or middle-aged men with ST segment elevation myocardial infarction, the "typical" cardiac patient now presents with acute coronary syndrome or with complications related to chronic hypertension or ischemic heart disease, including heart failure, sudden death, and atrial fibrillation. Analogously, structural heart disease is now dominated by degenerative valve or congenital disease, far more common than rheumatic disease. The changing clinical scene presents cardiovascular scientists with a number of opportunities and challenges, including taking advantage of high throughput technologies to elucidate complex disease mechanisms, accelerating development and implementation of evidence-based strategies, assessing evolving technologies of unclear value, addressing a global epidemic of cardiovascular disease, and maintaining high levels of innovation in a time of budgetary constraint and economic turmoil. PMID- 22315117 TI - Understanding the economic impact of introducing a new procedure: calculating downstream revenue of endobronchial ultrasound with transbronchial needle aspiration as a model. AB - Over the last decade, endobronchial ultrasound (EBUS) evolved into a validated and powerful diagnostic tool. Although it is integral to medical care in some health-care systems, others struggle to justify its purchase based on diminishing reimbursement. In analyzing its value to a health-care system, looking at procedural reimbursement alone will grossly underestimate its economic impact. Downstream revenue has been defined by administrators as revenue captured after patients use one hospital service and then use others. By analyzing consecutive EBUS cases and taking downstream revenue into account, $2.4 million in collections was attributed to 97 patients who were newly referred for this procedure. PMID- 22315118 TI - Severe bronchorrhea in a patient with bronchioloalveolar carcinoma. AB - Mucinous bronchioloalveolar carcinoma (BAC) can be associated with significant bronchorrhea. A 46-year-old man presented with BAC with 2,000 mL of sputum production on a daily basis, which prevented him from being extubated. As this condition is rare, there are only case reports outlining the therapy for the associated bronchorrhea. We used azithromycin, scopolamine, and inhaled fluticasone with moderate success. The initiation of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib, resulted in dramatic improvement in the volume of pulmonary secretions produced. The patient's EGFR mutation status was subsequently found to be negative, which supports the hypothesis that the mechanism of reduction of bronchorrhea is independent of the antiproliferative effect of the drug. PMID- 22315119 TI - Polymyxin use associated with respiratory arrest. AB - The polymyxins (polymyxin B and E) are bactericidal polypeptide antibiotics first discovered in 1947 and used for the treatment of gram-negative bacterial infections. Renal and neurologic toxicities coupled with the increasing availability of effective alternatives led to declining use in the 1960s. The emergence of multidrug-resistant organisms in the past decade has resulted in a resurgence in the use of polymyxins in critically ill patients, yet the side effects are not well known. We report two cases of respiratory arrest likely due to polymyxin B infusions in the context of a 10-fold increase in the use of polymyxin B in our institution over the past 10 years. PMID- 22315120 TI - Severity scoring in the critically ill: part 2: maximizing value from outcome prediction scoring systems. AB - Part 2 of this review of ICU scoring systems examines how scoring system data should be used to assess ICU performance. There often are two different consumers of these data: lCU clinicians and quality leaders who seek to identify opportunities to improve quality of care and operational efficiency, and regulators, payors, and consumers who want to compare performance across facilities. The former need to know how to garner maximal insight into their care practices; this includes understanding how length of stay (LOS) relates to quality, analyzing the behavior of different subpopulations, and following trends over time. Segregating patients into low-, medium-, and high-risk populations is especially helpful, because care issues and outcomes may differ across this severity continuum. Also, LOS behaves paradoxically in high-risk patients (survivors often have longer LOS than nonsurvivors); failure to examine this subgroup separately can penalize ICUs with superior outcomes. Consumers of benchmarking data often focus on a single score, the standardized mortality ratio (SMR). However, simple SMRs are disproportionately affected by outcomes in high risk patients, and differences in population composition, even when performance is otherwise identical, can result in different SMRs. Future benchmarking must incorporate strategies to adjust for differences in population composition and report performance separately for low-, medium- and high-acuity patients. Moreover, because many ICUs lack the resources to care for high-acuity patients (predicted mortality >50%), decisions about where patients should receive care must consider both ICU performance scores and their capacity to care for different types of patients. PMID- 22315121 TI - Sleep-related problems in neurologic diseases. AB - There is a strong association between sleep-related problems and neurologic diseases. Neurologic diseases of the CNS can directly cause sleep problems when sleep-wake mechanisms associated with the ascending reticular activating system are involved. The major sleep disorders associated with neurologic problems are outlined in the International Classification of Sleep Disorders, 2nd edition, as hypersomnias of central origin, sleep-related breathing disorders, the insomnias, circadian rhythm sleep disorders, sleep-related movement disorders, parasomnias, and sleep-related epilepsy. In a patient with CNS disease and excessive sleepiness, sleep-related breathing disorders should be a first concern, given the known association between obstructive sleep apnea (OSA) and cerebrovascular disease and the potential confounding effects that OSA might have on an otherwise compromised ischemic CNS penumbra. A basic knowledge of the anatomy and physiology of the sleep-wake mechanisms provides a rationale for pharmacologic intervention. Nonpharmacologic treatments are also important, especially when sleep-related breathing disorders are a concern. In addition, as patients with neurologic diseases are often prone to the adverse effects of many medications, the specific treatment regimen for any given individual should always include good sleep hygiene practices that use cognitive behavioral therapy. PMID- 22315122 TI - Interpretation of plain chest roentgenogram. AB - Plain chest roentgenogram remains the most commonly ordered screening test for pulmonary disorders. Its lower sensitivity demands greater accuracy in interpretation. This greater accuracy can be achieved by adhering to an optimal and organized approach to interpretation. It is important for clinicians not to misread an abnormal chest radiograph (CXR) as normal. Clinicians can only acquire the confidence in making this determination if they read hundreds of normal CXRs. An individual should follow the same systematic approach to reading CXRs each time. All clinicians must make a concerted effort to read plain CXRs themselves first without reading the radiologist report and then discuss the findings with their radiology colleagues. Looking at the lateral CXR may shed light on 15% of the lung that is hidden from view on the posteroanterior film. Comparing prior films with the recent films is mandatory, when available, to confirm and/or extend differential diagnosis. This article outlines one of the many systematic approaches to interpreting CXRs and highlights the lesions that are commonly missed. A brief description of the limitations of CXR is also included. PMID- 22315123 TI - A 54-year-old man with an uncommon cause of left pleural effusion. PMID- 22315124 TI - Release of metal particles from needles used for endobronchial ultrasound-guided transbronchial needle aspiration. PMID- 22315125 TI - Obesity: another good reason to question the fixed FEV1/FVC ratio when diagnosing COPD. PMID- 22315126 TI - Macrolides in asthma. PMID- 22315127 TI - Racial differences influence health-related quality-of-life measurements. PMID- 22315128 TI - COPD and ischemic heart disease. PMID- 22315129 TI - Agreement between patients' self-report and physicians' prescriptions on nonsteroidal anti-inflammatory drugs and other drugs used in musculoskeletal disorders: the international Pharmacoepidemiologic General Research eXtension database. AB - PURPOSE: The use of prescription records for the assessment of exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) does not capture over-the-counter drug use. This study compared patients' self-reported use to physician's prescriptions for NSAIDs and other drugs used to treat musculoskeletal disorders (MSDs). METHODS: The international Pharmacoepidemiologic General Research eXtension database includes a network of general practitioners recruiting patients without reference to diagnoses or prescriptions. Data on all drug use across France within the 2 years preceding the date of inclusion (index date) were obtained from both patients' self-reports (PSRs) and physicians' prescription reports (PPRs). Patients' reports were obtained using a structured telephone interview combined with an interview guide containing a list of drugs commonly used. Comparisons were made on exposure to four categories of MSD drugs and three time windows up to 24 months before the index date. RESULTS: Agreement between physician and patient reports was assessed on 4152 patient-physician pairs. Bias- and prevalence-adjusted kappa values showed fair agreement for nonaspirin NSAIDs, moderate to fair for nonnarcotic analgesics, high for osteoarthritis and moderate to substantial for muscle relaxants. Over-the-counter drug use was associated with greater disagreement (OR = 2.21, 95%CI = 1.05-1.38). Age was not associated with disagreement. CONCLUSION: Differences between PSR and PPR in estimating the prevalence of MSD drug use varied by the type of drug and the elapsed time from the index date. The patient-assisted interview method used in this study showed better agreement with PPR compared with standard interviews, especially for long time windows and patients older than 65 years. Copyright (c) 2012 John Wiley & Sons, Ltd. PMID- 22315130 TI - Salivary alpha-amylase during pregnancy: diurnal course and associations with obstetric history, maternal demographics, and mood. AB - Diurnal patterns of salivary alpha amylase (sAA) in pregnant women have not previously been described. The current study employed ecological momentary assessment to examine the association between the diurnal sAA, obstetric history, maternal demographics, and mood during pregnancy. Saliva was self-collected by 83 pregnant women (89% White, age 25.3-43.0 years; mean gestational age 21.9 weeks, range 6-37 weeks; gravida 1-6) at home over three days. Results indicated that current pregnancy (gestational age and fetal sex) and maternal demographics were not related to diurnal sAA. In contrast, a history of previous miscarriage (Parameter = -.17; SE = .05; p < .05) was associated with an atypical diurnal pattern. Even after accounting for obstetric history, trait anxiety (Parameter = .16; SE = .04; p < .001) was associated with increased sAA over the day while chronic levels of fatigue (Parameter = -.06; SE = .03; p < .05) were associated with decreased sAA. In a separate model, we also tested the time varying covariation of sAA and mood. The effects of momentary mood were in contrast to those for trait mood. Both momentary depression (Parameter = .22; SE = .09; p < .01) and vigour/positive mood (Parameter = .12; SE = .04; p < .001) were associated with momentary increases in sAA while momentary anxiety and fatigue were not related to sAA. The findings suggest that basal sAA during pregnancy is sensitive to emotional arousal. Evaluating diurnal patterns of sAA holds promise for advancing understanding of how emotional arousal during pregnancy may affect fetal development. PMID- 22315131 TI - Willingness to use tamoxifen to prevent breast cancer among diverse women. AB - Use of chemoprevention to prevent development of breast cancer among high-risk women has been limited despite clinical evidence of its benefit. Our goals were to determine whether knowledge of the benefits and risks of tamoxifen affects a woman's willingness to take it to prevent breast cancer, to define factors associated with willingness to take tamoxifen, and to evaluate race/ethnic differences. Women, ages 50-80, who identified as African American, Asian, Latina, or White, and who had at least one visit to a primary care physician in the previous 2 years, were recruited from ambulatory practices. After a screening telephone survey, women completed an in-person interview in their preferred language. Multivariate regression models were constructed to examine the associations of demographic characteristics, numeracy, breast cancer history, and health knowledge with willingness to take tamoxifen. Over 40% of the women reported they would likely take tamoxifen if determined to be at high risk, and 31% would be somewhat likely to do so. Asian women, those with no insurance, and those with less than high school education were significantly more likely to be willing to take tamoxifen. Higher scores on numeracy and on breast cancer knowledge were also associated with willingness to take tamoxifen. A higher tamoxifen knowledge score was inversely related to willingness to take the drug. Factors affecting women's willingness to take breast cancer chemoprevention drugs vary and are not determined solely by knowledge of risk/benefit or risk perception. PMID- 22315132 TI - Health-related quality of life in male breast cancer patients. AB - The objective of this study is to investigate health-related quality of life (HRQoL) in male breast cancer patients. Data of 20,673 patients diagnosed with primary breast cancer (male: n = 84) who completed a questionnaire after discharge from hospital were analysed. HRQoL (SF-36), age, sex, education, native language, insurance status, and partnership status were measured. Cancer staging, treatment (partial mastectomy vs. radical mastectomy), and cancer site were indicated by the clinicians. The HRQoL scores of male breast cancer patients were compared with reference populations. Differences in HRQoL scores between men and women were compared using t tests and regression analysis. Compared to female breast cancer patients, male patients scored significantly higher on seven of eight subscales (physical functioning, role functioning-physical and emotional, bodily pain, vitality, social functioning, and mental health) in the regression analysis. Compared to the reference populations (general male population, men aged 61-70, and the cancer-affected population), male breast cancer patients scored lower on SF-36 subscales on average, with major differences in emotional and physical role functioning. The results suggest that male breast cancer patients may need early interventions that specifically target role functioning, which is severely impaired compared to the male reference population. Future research needs to assess HRQoL with cancer-specific questionnaires and longitudinal designs also focussing on male patients in breast centres. PMID- 22315133 TI - 14-3-3sigma expression is associated with poor pathological complete response to neoadjuvant chemotherapy in human breast cancers. AB - 14-3-3sigma is a tumor suppressor gene induced by p53 in response to DNA damage and reportedly associated with resistance to chemotherapy. The aim of this study was to investigate whether 14-3-3sigma expression is also associated with resistance to neoadjuvant chemotherapy consisting of paclitaxel followed by 5 FU/epirubicin/cyclophosphamide (P-FEC) in human breast cancer patients. A total of 123 primary breast cancer patients treated with neoadjuvant chemotherapy (P FEC) were included in this study. Immunohistochemistry of 14-3-3sigma and p53 as well as direct sequencing of TP53 were performed using the tumor biopsy samples obtained prior to neoadjuvant chemotherapy. Thirty-eight of the tumors (31%) were positive for 14-3-3sigma. There was no significant association between 14-3 3sigma expression and TP53 mutation or p53 expression. However, 14-3-3sigma expression showed a significantly (P=0.009) negative association with pathological complete response (pCR) to P-FEC, and multivariate analysis demonstrated that only 14-3-3sigma (P=0.015) and estrogen receptor (P=0.021) were significantly and independently associated with pCR. The combination of 14-3 3sigma expression and TP53 mutation status had an additive negative effect on pCR, i.e., pCR rates were 45.5% for 14-3-3sigma negative/TP53 mutant tumors, 24.6% for 14-3-3sigma negative/TP53 wild tumors, 23.1% for 14-3-3sigma positive/TP53 mutant tumors, and 0% for 14-3-3sigma positive/TP53 wild tumors. These results demonstrate that 14-3-3sigma expression is significantly associated with resistance to P-FEC and this association is independent of other biological markers. The combination of 14-3-3sigma expression and TP53 mutation status has an additively negative effect on the response to P-FEC. PMID- 22315134 TI - Economic evaluation of the 70-gene prognosis-signature (MammaPrint(r)) in hormone receptor-positive, lymph node-negative, human epidermal growth factor receptor type 2-negative early stage breast cancer in Japan. AB - The 70-gene prognosis-signature is validated as a good predictor of recurrence for hormone receptor-positive (ER+), lymph node-negative (LN-), human epidermal growth factor receptor type 2-negative (HER2-) early stage breast cancer (ESBC) in Japanese patient population. Its high cost and potential in avoiding unnecessary adjuvant chemotherapy arouse interest in its economic impact. This study evaluates the cost-effectiveness of including the assay into Japan's social health insurance benefit package. An economic decision tree and Markov model under Japan's health system from the societal perspective is constructed with clinical evidence from the pool analysis of validation studies. One-way sensitivity analyses are also performed. Incremental cost-effectiveness ratio is estimated as Y3,873,922/quality adjusted life year (QALY) (US$43,044/QALY), which is not more than the suggested social willingness-to-pay for one QALY gain from an innovative medical intervention in Japan, Y5,000,000/QALY (US$55,556/QALY). However, sensitivity analyses show the instability of this estimation. The introduction of the assay into Japanese practice of ER+, LN-, HER2- ESBC treatment by including it to Japan's social health insurance benefit package has a reasonable chance to be judged as cost-effective and may be justified as an efficient deployment of finite health care resources. PMID- 22315135 TI - The single-nucleotide polymorphisms +936 C/T VEGF and -710 C/T VEGFR1 are associated with breast cancer protection in a Spanish population. AB - Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis and thereby involved in the development and progression of solid tumours. The association between polymorphisms of angiogenesis pathway genes and risk of breast cancer (BC) has been widely studied, but the results are not conclusive. This information is especially limited in Spanish women, so we decided to conduct a case-control study. Here, we selected four commonly studied polymorphisms in VEGF, rs3025039 (known as +936 C/T), rs1109324, rs154765 and rs833052, one polymorphism at the promoter of the VEGFR1 (-710 C/T) and another in the FGF2, rs1449683, gene to explore their association with BC susceptibility. Genotyping was performed by TaqMan SNP assays and polymerase chain reaction-restriction fragment length polymorphis (PCR-RFLP) on 453 patients and 461 controls in a population from Valencia (Spain). We observed that women carriers of +936 CT + TT VEGF genotypes have a protective effect concerning this disease (p = 0.014; OR 0.67, 95% CI 0.48-0.92) in the global group of patients. The haplotype TGAC of VEGF (rs3025039, rs1109324, rs154764 and rs833052) shows a reduction of the risk to develop BC (p = 3e-04; OR 0.48, 95% CI 0.32-0.72). Furthermore, we found that carriers of -710 CT + TT VEGFR1 genotypes have also a protective effect (p = 0.039; OR 0.55, 95% CI 0.31-0.98). When we stratified by groups of ages these associations were maintained. Our data report for the first time the association of the polymorphism -710 C/T VEGFR1 with BC. Additional experiments focused on VEGF-A, VEGFR1 and sVEGFR1 gene expression demonstrated that carriers of T allele at -710 C/T VEGFR1 genotype have higher levels of sVEGFR1/VEGF-A than the C/C genotype carriers. This was consistent with the hypothesis that this polymorphism may act as low penetrance risk factor. The data provided suggest that +936 C/T VEGF and -710 C/T VEGFR1 genotypes are likely important genetic markers of susceptibility to BC. PMID- 22315136 TI - The results of treatment of children with metastatic Wilms tumours (WT) in an African setting: do liver metastases have a negative impact on survival? AB - BACKGROUND: From Africa, where socio-economic circumstances differ from the developed world, there are no data regarding the influence of liver metastases on survival of children with Wilms tumour. PROCEDURE: One hundred fifty new patients with WT were seen between 2002 and 2010, 45 (30%) had metastases at diagnosis. Seven patients had bilateral disease with additional visceral metastases. Nine patients who developed liver metastases during treatment were excluded. The site of metastases and the results of pretreatment biopsies were retrieved. Neo adjuvant chemotherapy was combined with nutritional resuscitation, and aggressive supportive care. Post-operative treatment was determined by stage and histology. RESULTS: Liver metastases were present in 19 (42%) patients but were the sole metastatic site in only 4 (9%). Overall survival at 5 years was 58.5%. Event Free Survival was 54%. Thirty-three (73%) had favourable histology, nine unfavourable and undetermined in three. No influence of histology on outcome was evident. Three patients had resection of persistent liver metastases. The pattern of metastatic disease had no influence on outcome. Despite aggressive supportive care two patients (4%) died within a week of presentation. Two patients died of chemotoxicity and two of complications following biopsy. Eight patients (17%) were lost to follow-up of whom five were on palliative treatment only. CONCLUSIONS: In Africa liver metastases do not appear to worsen the prognosis of children with Stage IV WT. Despite the poor socio-economic circumstances survival is comparable to other countries. PMID- 22315137 TI - A large-scale (19)F MRI-based cell migration assay to optimize cell therapy. AB - Adoptive transfer of cells for therapeutic purposes requires efficient and precise delivery to the target organ whilst preserving cell function. Therefore, therapeutically applied cells need to migrate and integrate within their target tissues after delivery, e.g. dendritic cells (DCs) need to migrate to lymph nodes to elicit an antigen-specific immune response. Previous studies have shown that inappropriate cell delivery can hinder DC migration and result in insufficient immune induction. As migration can be extremely difficult to study quantitatively in vivo, we propose an in vitro assay that reproduces key in vivo conditions to optimize cell delivery and migration in vivo. Using DC migration along a chemokine gradient, we describe here a novel (19)F MR-based, large-scale, quantitative assay to measure cell migration in a three-dimensional collagen scaffold. Unlike conventional migration assays, this set-up is amenable to both large and small cell numbers, as well as opaque tissue samples and the inclusion of chemokines or other factors. We labeled primary human DCs with a (19)F label suitable for clinical use; (0.5-15) * 10(6) cells in the scaffolds were imaged sequentially, and migration was assessed using two independent methods. We found no migration with larger numbers of cells, but up to 3% with less than one million cells. Hence, we show that the cell density in cell bolus injections has a decisive impact on migration, and this may explain the limited migration observed using large cell numbers in the clinic. PMID- 22315138 TI - PL1 fusion gene: a novel visual selectable marker gene that confers tolerance to multiple abiotic stresses in transgenic tomato. AB - Visual selectable markers, including the purple color caused by the accumulation of anthocyanins, have been proposed for use as antibiotic-free alternatives. However, the excessive accumulation of anthocyanins seriously inhibits the growth and development of transgenic plants. In our study, the AtDWF4 promoter from Arabidopsis and the tomato LeANT1 gene, encoding a MYB transcription factor, were used to construct the PL1 fusion gene to test whether it could be used as a visual selectable marker gene for tomato transformation. All the PL1 transgenic shoots exhibited intense purple color on shoot induction medium. In the transgenic tomato plants, PL1 was highly expressed in the cotyledons, but expressed only slightly in the true leaves and other organs. The expression of PL1 had no significantly adverse effects on the growth or development of the transgenic tomato plants, and conferred tolerance to multiple abiotic stresses in them. With the "cut off green shoots" method, multiple independent 35S::GFP transgenic tomato lines were successfully obtained using PL1 as the selectable marker gene. These results suggest that PL1 has potential application of visual selectable marker gene for tomato transformation. PMID- 22315139 TI - Evaluation of oxidative stress markers and vascular risk factors in patients with diabetic peripheral neuropathy. AB - Diabetic peripheral neuropathy (DPN) is one of the most common diabetic chronic complications. The pathogenesis of DPN is complex and involves an intertwined array of mechanisms. The purposes of this study were to evaluate the association of oxidative stress and vascular risk factors with the prevalence of DPN and to determine the role of these biochemical parameters in the prognosis of DPN. One hundred patients with type 2 diabetes mellitus and 40 clinically healthy individuals were evaluated. The patients were divided into two groups. Group 1 included 40 diabetic patients without peripheral neuropathy, and group 2 consisted of 60 patients with DPN. Erythrocytes glutathione (GSH) level, plasma malondialdehyde (MDA), nitrite/nitrate (NOx) and homocysteine (Hcy) levels as well as serum ceruloplasmin (Cp), total antioxidants (TAO), endothelin-1 (ET-1) levels and gamma-glutamyl transferase (GGT) activity were estimated. A significant decrease of erythrocyte GSH was observed in groups 1 and 2 relative to the controls. An increase in glycosylated haemoglobin (HbA1c), MDA, NOx, GGT, Cp, TAO, Hcy and ET-1 was noted in patients with DPN. In conclusion, oxidative stress biomarkers and vascular risk factors could be important in the pathogenesis of DPN. The measurement of serum GGT and Hcy in addition to HbA1c and disease duration could facilitate the early detection of neuropathy in diabetic patients. PMID- 22315140 TI - Novel hollow mesoporous 1D TiO2 nanofibers as photovoltaic and photocatalytic materials. AB - Hollow mesoporous one dimensional (1D) TiO(2) nanofibers are successfully prepared by co-axial electrospinning of a titanium tetraisopropoxide (TTIP) solution with two immiscible polymers; polyethylene oxide (PEO) and polyvinylpyrrolidone (PVP) using a core-shell spinneret, followed by annealing at 450 degrees C. The annealed mesoporous TiO(2) nanofibers are found to having a hollow structure with an average diameter of 130 nm. Measurements using the Brunauer-Emmett-Teller (BET) method reveal that hollow mesoporous TiO(2) nanofibers possess a high surface area of 118 m(2) g(-1) with two types of mesopores; 3.2 nm and 5.4 nm that resulted from gaseous removal of PEO and PVP respectively during annealing. With hollow mesoporous TiO(2) nanofibers as the photoelectrode in dye sensitized solar cells (DSSC), the solar-to-current conversion efficiency (eta) and short circuit current (J(sc)) are measured as 5.6% and 10.38 mA cm(-2) respectively, which are higher than those of DSSC made using regular TiO(2) nanofibers under identical conditions (eta = 4.2%, J(sc) = 8.99 mA cm(-2)). The improvement in the conversion efficiency is mainly attributed to the higher surface area and mesoporous TiO(2) nanostructure. It facilitates the adsorption of more dye molecules and also promotes the incident photon to electron conversion. Hollow mesoporous TiO(2) nanofibers with close packing of grains and crystals intergrown with each other demonstrate faster electron diffusion, and longer electron recombination time than regular TiO(2) nanofibers as well as P25 nanoparticles. The surface effect of hollow mesoporous TiO(2) nanofibers as a photocatalyst for the degradation of rhodamine dye was also investigated. The kinetic study shows that the hollow mesoporous surface of the TiO(2) nanofibers influenced its interactions with the dye, and resulted in an increased catalytic activity over P25 TiO(2) nanocatalysts. PMID- 22315141 TI - Outcome measurement in behavioural sciences: a view on how to shift attention from means to individuals and why. AB - Outcome studies in biomedical research usually focus on testing mean changes across samples of subjects and, in so doing, often obscure changes in individuals. These changes, however, may be very informative in studies in which large or homogeneous samples are unavailable and mechanisms of action are still under scrutiny, as is often the case for trials on new exercise treatments. Single measurements of change may be valid, provided that the reliability of the measurement process (i.e. instrument and procedure combined) was ascertained in a dedicated study in which appropriate statistical models and algorithms were applied. This article summarizes the conceptual steps that allow the calculation of the minimal real difference (MRD, also known as the minimal detectable change), on the basis of the assessment of reliability using an intraclass correlation coefficient. Individuals who show changes beyond the MRD can be reliably considered as changed. A numerical example of an MRD calculation is shown, and the pros and cons of the mean change and the MRD approach are discussed. PMID- 22315142 TI - Support to students with Asperger syndrome in higher education--the perspectives of three relatives and three coordinators. AB - An increasing number of students with disabilities attend institutes of higher education (HE). Among this group are persons with Asperger syndrome (AS). Persons with AS have a cognitive impairment that can interfere with their studies and the ability to describe their needs and ask for support. This study deals with an assessment of the support services for students with AS from the perspectives of the students' relatives and the students' service providers at the universities they attend. The aim of this study was to investigate (a) earlier experiences and events in relation to the transition of students with AS to higher education, according to the relatives' perceptions of how these experiences and events affect university studies; and (b) the perceptions of both the relatives of students with AS and the coordinators for students with disabilities with respect to the study environment and support for students with AS. The approach is a case study methodology involving relatives and university coordinators for three students with AS. The coordinators' way of working with students with disabilities is primarily based on the coordinators' own ideas. No specific organizational routines exist for students with AS. The results reveal that the needs of students with AS have to be made explicit and must be incorporated into the support system. Relatives lack information about the situation and opportunities to engage in collaboration. Universities must adapt the support system to the cognitive impairments experienced by AS students and the difficulties of their everyday lives. The relatives of students with AS may play the central role in supporting the students and in understanding their impairment. PMID- 22315143 TI - Reliability and clinical significance of mobility and balance assessments in multiple sclerosis. AB - The aim of the study was to establish the test-retest reliability, clinical significance and precision of four mobility and balance measures - the Timed 25 Foot Walk, Six-minute Walk, Timed Up and Go and the Berg Balance Scale - in individuals moderately affected by multiple sclerosis. Twenty four participants with multiple sclerosis (Extended Disability Status Score 5-6.5) were assessed on four measures of mobility and balance. The Timed 25-Foot Walk, Six-minute Walk and Timed Up and Go mobility outcome measures and the Berg Balance Scale were assessed by one assessor one week apart. Intraclass correlation coefficient (ICC) analysis was carried out to determine reliability. Minimal detectable change values were calculated to determine clinical significance; the standard error of each measurement was calculated to assess precision. All four outcome measures were found to be reliable: Timed 25-Foot Walk ICC=0.94, Six-minute Walk Test ICC=0.96, Timed Up and Go ICC=0.97 and Berg Balance Scale ICC=0.96. Minimal detectable change values were as follows: Timed 25-Foot Walk=12.6 s, Six-minute Walk Test=76.2 m, Timed Up and Go=10.6 s and Berg Balance Scale=7 points. Standard errors of measurement were as follows: Timed 25-Foot Walk=4.56 s, Six minute Walk Test=27.48 m, Timed Up and Go=3.81 s and Berg Balance Scale=3 points. The test-retest reliability of these four outcome measures was found to be good. The calculated clinical significance and precision of these measures highlight the problems of assessing a heterogeneous clinical population. PMID- 22315144 TI - Single particle analysis using fluidic, optical and electrophoretic force balance in a microfluidic system. AB - A unique microfluidic system is developed which enables the interrogation of a single particle by using multiple force balances from a combination of optical force, hydrodynamic drag force, and electrophoretic force. Two types of polystyrene (PS) particles with almost identical size and refractive index (plain polystyrene (PS) particle - mean diameter: 2.06 MUm, refractive index: 1.59; carboxylated polystyrene (PS-COOH) particles - mean diameter: 2.07 MUm, refractive index: 1.60), which could not be distinguished by optical chromatography, reveal different electrokinetic behaviors resulting from the difference in their surface charge densities. The PS-COOH particles, despite their higher surface charge density when compared to the PS particles, experience a lower electrophoretic force, regardless of ionic strength. This phenomenon can be understood when the more prominent polarization of the counter ion cloud surrounding the PS-COOH particles is considered. The surface roughness of the carboxylated particles also plays an important role in the observed electrokinetic behavior. PMID- 22315146 TI - Occurrence of spontaneous resolution of ketoprofen with a racemic crystal structure by simple crystallization under nonequilibrium preferential enrichment conditions. AB - Nearly racemic ketoprofen, which satisfies the requirements for the occurrence of preferential enrichment, was spontaneously resolved into the two enantiomers by simple crystallization under nonequilibrium conditions using high concentrations. PMID- 22315145 TI - Down-stream components of cytokinin signaling and the role of cytokinin throughout the plant. AB - Cytokinins constitute a class of plant hormones influencing numerous aspects of growth and development. These processes occur through the downstream components of the cytokinin signaling pathway after its perception and signal transduction. The importance of these downstream signaling components has been revealed through the use of both traditional genetic and advanced molecular approaches studying mutants and transgenic lines involving cytokinin and diverse plant growth and developmental processes. Interestingly, these effects are not always directly via cytokinin, but by interactions with other plants hormones or transcription factor cascades, which can involve regulatory loops that affect transcription as well as hormone concentrations. This review covers recent advancements in understanding the role of cytokinin via its signaling components, specifically the downstream responses regulators in controlling vital plant growth and developmental processes. PMID- 22315147 TI - Pharmacokinetics and pharmacodynamics of the novel PAR-1 antagonist vorapaxar in patients with end-stage renal disease. AB - PURPOSE: To determine whether impaired renal function alters the pharmacokinetics (PK) of vorapaxar or its ability to inhibit thrombin receptor agonist peptide (TRAP)-induced platelet aggregation. METHODS: This was an open-label study in which 8 patients with end-stage renal disease (ESRD) on hemodialysis and 7 matched (based on age, gender, weight, and height) healthy controls were administered a single 10-mg oral dose of vorapaxar. Blood samples for vorapaxar PK and pharmacodynamic analysis were collected predose and at frequent intervals up to 6 weeks postdose. RESULTS: Mean vorapaxar bioavailability (based on area under the curve of plasma vorapaxar concentration over time) was identical in the two subject groups; the ESRD/healthy geometric mean ratio (GMR, expressed in percent) was 98. Mean maximum observed plasma concentration (77.4-98.2 ng/mL) was numerically lower in patients with ESRD compared with matched controls (GMR=76; 90% confidence interval=48 to 118). Median time of maximum observed plasma concentration was 2 h in both subject groups. The observed means for elimination half-life were 186 and 231 h in the ESRD and control groups, respectively. Inhibition of platelet aggregation was similar in the two groups. Four out of 15 (27%) subjects reported adverse events, all of which were characterized by the investigator as mild and unrelated to treatment. CONCLUSIONS: ESRD had no clinically relevant effect on the PK profile of vorapaxar or its ability to inhibit TRAP-induced platelet aggregation. PMID- 22315148 TI - Epistaxis and other haemorrhagic events associated with the smoking cessation medicine varenicline: a case series from two national pharmacovigilance centres. AB - PURPOSE: To present a case series of haemorrhagic events associated with varenicline identified from the New Zealand (NZ) and Netherlands national pharmacovigilance centres and propose a possible mechanism for these adverse events. METHODS: Reports of epistaxis and other haemorrhagic events (in all system organ classes excluding gynaecological) associated with varenicline were identified and assessed in both the NZ Intensive Medicines Monitoring Programme (IMMP) and the Netherlands Pharmacovigilance Centre Lareb (Lareb). Additional reports were identified from the World Health Organisation Uppsala Monitoring Centre (WHO-UMC) datasets, and these also underwent causality assessment. RESULTS: A total of 30 reports of haemorrhagic events were identified by the NZ IMMP (16 reports) and Lareb (14 reports). Six cases of epistaxis were identified, and four patients had a positive dechallenge on withdrawal of varenicline, suggesting a causal association. Another five reports of gingival bleeding were identified, with three patients having a positive dechallenge. Another patient who experienced haemoptysis while taking varenicline had a positive dechallenge and a positive rechallenge. In the WHO datasets, a further 49 reports of epistaxis, 39 reports of haemoptysis and 21 reports of thrombocytopenia were identified. A plausible mechanism for haemorrhagic events associated with varenicline may be a result of interaction with the serotonin (5-HT) receptor system and transporter. CONCLUSIONS: This is the first specific investigation of haemorrhagic events associated with varenicline. The results of our assessment of reports identified by two national pharmacovigilance centres suggest that there may be causal relationship between varenicline and these adverse events. PMID- 22315150 TI - Comparative adherence to oxybutynin or tolterodine among older patients. PMID- 22315149 TI - Pharmacovigilance in children in Camaguey Province, Cuba. AB - PURPOSE: Our aim was to describe the adverse drug reactions (ADRs) detected following increased education about pharmacovigilance and drug toxicity in children in Camaguey Province, Cuba. METHODS: Over a period of 24 months (January 2009 to December 2010), all reports of suspected ADRs in children to the Provincial Pharmacovigilance Centre in Camaguey Province were analysed. ADRs were classified in relation to causality and severity. RESULTS: There were 533 reports involving suspected ADRs in children in the period. Almost one third of the reports received were classified as moderate (155, 29%) or severe (10, 2%). There was one fatality in association with the use of ceftriaxone. Vaccines and antibiotics were responsible for most of the ADR reports (392, 74%) and for all ten severe ADRs. After an intensive educational package, both within the community and the Children's Hospital, the number of reports increased from 124 in 2008 to 161 in 2009 and 372 in 2010. This was equivalent to a reporting rate of 879 and 2,031 reports per million children per year for 2009 and 2010, respectively. CONCLUSIONS: The incidence of ADRs in children Camaguey Province, Cuba, is greater than previously reported. An educational intervention about pharmacovigilance and drug toxicity in children can improve the reporting of ADRs. PMID- 22315151 TI - Contribution of infectious disease consultation toward the care of inpatients being considered for community-based parenteral anti-infective therapy. AB - BACKGROUND: In the acute care setting in a multidisciplinary healthcare environment, the contribution of infectious disease (ID) specialists to overall patient care is difficult to measure. This study attempts to quantify the contribution of ID specialists when consulted for an activity specific to ID practice, community-based parenteral anti-infective therapy (CoPAT). METHODS: In February 2010, an electronic form for requesting ID consultations was introduced in the computerized provider order entry (CPOE) system at the Cleveland Clinic. This allowed for easy identification of ID consultations for CoPAT. Hospital records for all patients with CoPAT consultation requests between February 11, 2010 and May 15, 2010 were reviewed for specific defined contributions in the domains of optimization of antimicrobial therapy, significant change in patient assessment, and additional medical care contribution. RESULTS: Over a 3-month period, there were 263 CoPAT consultation requests via CPOE, of which 172 were initial consultations and 91 reconsultations. Antimicrobial treatment was optimized in 84%, a significant change in patient assessment made in 52%, and additional medical care contribution provided in 71% of consultations. In 33% of consultations, there was contribution in all 3 domains. CoPAT was deemed not to be necessary in 27%. For patients requiring CoPAT, effective care transition from the inpatient to outpatient setting was assured at least 86% of the time. CONCLUSION: Infectious disease consultation before discharge on parenteral antibiotics adds value by contributing substantially to inpatient care, and providing antimicrobial stewardship and continuity of care at a critical patient care transition point. PMID- 22315152 TI - Electronic healthcare databases for active drug safety surveillance: is there enough leverage? AB - PURPOSE: To provide estimates of the number and types of drugs that can be monitored for safety surveillance using electronic healthcare databases. METHODS: Using data from eight European databases (administrative claims, medical records) and in the context of a cohort study, we determined the amount of drug exposure required for signal detection across varying magnitudes of relative risk (RR). We provide estimates of the number and types of drugs that can be monitored as a function of actual use, minimal detectable RR, and empirically derived incidence rates for the following adverse events: (i) acute myocardial infarction; (ii) acute renal failure; (iii) anaphylactic shock; (iv) bullous eruptions; (v) rhabdomyolysis; and (vi) upper gastrointestinal bleeding. We performed data simulation to see how expansion of database size would influence the capabilities of such system. RESULTS: Data from 1,947,452 individuals (59,594,132 person-years follow-up) who used 2,289 drugs in the EU-ADR network show that for a frequent event such as acute myocardial infarction, there are 531 drugs (23% of total) for which an association with RR = 2, if present, can be investigated. For a rare event such as rhabdomyolysis, there are 19 drugs (1%) for which an association of same magnitude can be investigated. CONCLUSION: Active surveillance using healthcare data-based networks for signal detection is feasible, although the leverage to do so may be low for infrequently used drugs and for rare outcomes. Extending database network size to include data from heterogeneous populations and increasing follow-up time are warranted to maximize leverage of these surveillance systems. PMID- 22315153 TI - In situ randomised trial to investigate the occluding properties of two desensitising toothpastes on dentine after subsequent acid challenge. AB - OBJECTIVES: The aim of the study was to determine in situ the relative abilities of two desensitising toothpastes to occlude dentinal tubules with or without acid challenge. MATERIALS AND METHODS: The study design was a single centre, randomised, split mouth crossover model examining four treatments over two periods. The primary outcome was the degree of occlusion proffered by two desensitising toothpastes [Sensodyne(r) Rapid Relief (8% strontium acetate, 1040 ppm sodium fluoride) and Colgate(r) Sensitive Pro-ReliefTM daily (8% arginine, 1450 ppm sodium monofluorophosphate)], a standard toothpaste (1450 ppm sodium fluoride) and water, after acid challenge. Healthy adult volunteers wore bi lateral lower buccal appliances each with two dentine sections, receiving two treatments per study period. Samples were brushed twice a day with treatment, with two additional 3-min extra-oral acidic challenges applied ex vivo on days 3 and 4. A secondary outcome was the degree of occlusion attained in the absence of acid challenge. Examiners blinded to the study assessed occlusion by visual score of post-treatment scanning electron microscope images. RESULTS: All 28 participants completed the study. In the absence of acid challenge, occlusion scores for both desensitising toothpastes were similar and significantly better than control scores (p < 0.02). After acid challenge both desensitising toothpastes occluded more effectively than controls; however, occlusion scores for the strontium acetate paste were significantly greater than those of the arginine paste (p < 0.02). CONCLUSIONS: The occluding properties of the strontium acetate toothpaste were significantly more robust after acid challenge than those of the arginine toothpaste. CLINICAL RELEVANCE: Patients with hypersensitivity, regularly imbibing dietary acidic drinks, should be advised that Sensodyne(r) Rapid Relief provides robust tubule occlusion despite repeated acidic challenges. PMID- 22315154 TI - Occurrence of erectile dysfunction, testosterone deficiency syndrome and metabolic syndrome in patients with abdominal obesity. Where is a sufficient level of testosterone? AB - AIM: The aim of this study was to determine the prevalence of erectile dysfunction (ED), testosterone deficiency syndrome (TDS), and metabolic syndrome in patients with abdominal obesity (AO) and the prevalence of morbidity at different levels of testosterone (TST). BACKGROUND: Male sex hormones play an important role in ED and variety of TDS and may have influence on the development of metabolic syndrome. The number of men with AO which constitutes a serious health risk is continuously growing. Currently, there are different views that TST levels are already insufficient, and the patient should benefit from treatment. OBJECTIVES: This study examined the association between ED, testosterone level and metabolic syndrome in men with AO. DESIGN, SETTING, AND PARTICIPANTS: The study was carried out in an outpatient urology center of Urology Clinic and Obesity Center of the Clinic of Internal Medicine. There were 167 participants-men with AO which were examined as part of preventive examination. METHODS: Hormonal, a complete urological and internal evaluation was carried out in every patient. RESULTS AND LIMITATIONS: We found some degree of ED in 73% (122/167) in men with AO. The TST levels below 14 nmol/l had of these 122 patients 84 patients (68.9%) and 49 patients (40.2%) below 10 nmol/l. In this group of patients, we found 103/167 patients (61.7%) with metabolic syndrome. When we compared TST level and morbidity, we found significantly more patients with diabetes mellitus (DM), hypertension and dyslipidemia in group with TST below 10 nmol/l. We also found difference in the levels of HDL cholesterol and triglycerides in the group of patients with TST 10-14 and over 14 nmol/l. CONCLUSION: Patients over 40 years of age with AO and ED should also be examined for TDS and metabolic syndrome. In this group of patients we found that 113/167 patients (67.6%) had total TST below 14 nmol/l, and sufficient level of TST seems to be above this level. PMID- 22315155 TI - Goserelin versus leuprolide in the chemical castration of patients with prostate cancer. AB - PURPOSE: To evaluate the relative efficiency of leuprolide 3.75 mg, leuprolide 7.5 mg, and goserelin 3.6 mg in relation to the reduction in serum testosterone, regarding the levels of castration. MATERIALS AND METHODS: We evaluated prospectively 60 randomized patients with advanced prostate carcinoma, with indication for hormone blockade. The patients were divided into 3 groups of 20: Group (1) received leuprolide 3.75 mg; Group (2) received leuprolide 7.5 mg; and Group (3) received goserelin 3.6 mg. All groups were treated with monthly application of the respective drugs. The patients' levels of serum testosterone were evaluated in two moments: before the treatment and 3 months after the treatment. RESULTS: The patients' ages were similar within the three groups, with a median of 72, 70, and 70 in groups 1, 2, and 3, respectively. Of the patients that received leuprolide 3.75 mg, leuprolide 7.5 mg, and goserelin 3.6 mg, 26.3, 25, and 35%, respectively, did not reach castration levels, considering a testosterone cutoff <= 50 ng/dl. And 68.4, 30, and 45%, respectively, did not reach castration levels, considering a testosterone cutoff <= 20 ng/dl. CONCLUSIONS: There were no statistically significant differences in the levels of castration when comparing leuprolide 3.75 mg, leuprolide 7.5 mg, and goserelin 3.6 mg, altogether. When compared in groups of two, there was a statistically significant difference between leuprolide 3.75 mg and leuprolide 7.5 mg, the latter presented better results in reaching castration levels, cutoff <= 20 ng/dl. The importance of this difference, however, must be measured with caution, since the comparison of the three groups simultaneously did not reach the established significance level, even though it came close. PMID- 22315156 TI - The role of free to total PSA ratio in prediction of extracapsular tumor extension and biochemical recurrence after radical prostatectomy in patients with PSA between 4 and 10 ng/ml. AB - OBJECTIVES: The prognostic value of free to total PSA ratio (F/T PSA) in patients eligible for radical prostatectomy (RP) is controversial. The aim of the present study was to evaluate correlation of F/T PSA with tumor extracapsular extension (ECE) and biochemical recurrence (BR) at long-term follow-up. PATIENT AND METHODS: Clinical and pathological data were prospectively gathered from 200 patients treated with RP for clinically localized prostate cancer (PCa) and PSA between 4 and 10 ng/mL. Correlations of preoperative variables including F/T PSA with ECE and BR were evaluated with uni- and multivariate analysis. Adjunctive analyses evaluated the association of PSA F/T with other pathological results. The relationship between preoperative F/T PSA and BR was also assessed with Kaplan-Meier survival analysis. RESULTS: Lower F/T PSA was significantly correlated with ECE (p = 0.0063), higher GS (p = 0.0054), and seminal vesicles involvement (p = 0.0047). The F/T PSA value of 14% provided the greatest discrimination in predicting ECE. At multivariate analysis, F/T PSA did not achieve the statistical significance for predicting ECE independently. At a mean (median, range) follow-up of 52 (48, 14-116) months, preoperative F/T PSA resulted significantly correlated with BR (p = 0.001). At the Kaplan-Meier survival analysis, the 5-year BR free survival rate resulted 89.3 and 68.9% in the group with F/T PSA >14 and <=14 ng/mL, respectively (log rank p = 0.0022). At Cox proportional hazard model, only ECE resulted an independent predictor of BR (R = 2.646, p = 0.037). CONCLUSION: In patients with clinically localized PCa and PSA 4-10 ng/ml, lower F/T PSA was significantly associated with ECE, other adverse pathologic features, and with BR at the long-term follow-up, but only ECE resulted an independent predictor of BR in our series. PMID- 22315157 TI - Time sequence of the intensification of the liver glucose production induced by high-fat diet in mice. AB - It is well established that the development of insulin resistance shows a temporal sequence in different organs and tissues. Moreover, considering that the main aspect of insulin resistance in liver is a process of glucose overproduction from gluconeogenesis, we investigated if this metabolic change also shows temporal sequence. For this purpose, a well-established experimental model of insulin resistance induced by high-fat diet (HFD) was used. The mice received HFD (HFD group) or standard diet (COG group) for 1, 7, 14 or 56 days. The HFD group showed increased (P < 0.05 versus COG) epididymal, retroperitoneal and inguinal fat weight from days 1 to 56. In agreement with these results, the HFD group also showed higher body weight (P < 0.05 versus COG) from days 7 to 56. Moreover, the changes induced by HFD on liver gluconeogenesis were progressive because the increment (P < 0.05 versus COG) in glucose production from l-lactate, glycerol, l alanine and l-glutamine occurred 7, 14, 56 and 56 days after the introduction of the HFD schedule, respectively. Furthermore, glycaemia and cholesterolemia increased (P < 0.05 versus COG) 14 days after starting the HFD schedule. Taken together, the results suggest that the intensification of liver gluconeogenesis induced by an HFD is not a synchronous 'all-or-nothing process' but is specific for each gluconeogenic substrate and is integrated in a temporal manner with the progressive augmentation of fasting glycaemia. PMID- 22315158 TI - Early maternal care predicts reliance on social learning about food in adult rats. AB - Many vertebrates rely extensively on social information, but the value of information produced by other individuals will vary across contexts and habitats. Social learning may thus be optimized by the use of developmental or current cues to determine its likely value. Here, we show that a developmental cue, early maternal care, correlates with social learning propensities in adult rodents. The maternal behavior of rats Rattus norvegicus with their litters was scored over the first 6 days postpartum. Rat dams show consistent individual differences in the rate they lick and groom (LG) pups, allowing them to be categorized as high, low, or mid-LG mothers. The 100-day old male offspring of high and low-LG mothers were given the opportunity to learn food preferences for novel diets from conspecifics that had previously eaten these diets ("demonstrators"). Offspring of high-LG mothers socially learned food preferences, but offspring of low-LG mothers did not. We administered oxytocin to subjects to address the hypothesis that it would increase the propensity for social learning, but there were no detectable effects. Our data raise the possibility that social learning propensities may be both relatively stable throughout life and part of a suite of traits "adaptively programmed" by early developmental experiences. PMID- 22315159 TI - False-evidence ploys and interrogations: mock jurors' perceptions of false evidence ploy type, deception, coercion, and justification. AB - We studied mock jurors' evaluations of police false-evidence ploys across two false-evidence ploy information conditions (true or false confession). Study 1 participants evaluated lists of demeanor, testimonial, and scientific ploys and rated testimonial false-evidence ploys as more coercive than demeanor false evidence ploys. Participants in the false-confession condition rated false evidence ploys as more deceptive than did participants in the true-confession condition. Study 2 participants evaluated false-evidence ploy types within interrogation transcripts. Participants rated testimonial false-evidence ploys as more deceptive and coercive than demeanor false-evidence ploys; participants in the true-confession condition rated false-evidence ploys as more justified. Across studies, participants reading realistic transcripts rated false-evidence ploys as more deceptive and coercive. We discuss implications for scholars, attorneys, and interrogators. PMID- 22315160 TI - Voluntary private health insurance among the over 50s in Europe. AB - Using data from Survey of Health, Ageing and Retirement in Europe (SHARE), we investigate the determinants of voluntary private health insurance (VPHI) among the over 50s in 11 European countries and their effects on healthcare spending. First, we find that the main determinants of VPHI are different in each country, reflecting differences in the underlying healthcare systems, but in most countries, education levels and cognitive abilities have a strong positive effect on holding a VPHI policy. We also analyse the effect of holding a voluntary additional health insurance policy on out-of-pocket (OOP) healthcare spending. We adopt a simultaneous equations approach to control for self-selection into VPHI policy holding and find that, only in the Netherlands, VPHI policyholders have lower OOP spending than the rest of the population, whereas in some countries (Italy, Spain, Denmark and Austria), they spend significantly more. This could be due to not only increased utilisation but also cost-sharing measures adopted by the insurers to counter the effects of moral hazard and to keep adverse selection under control. PMID- 22315161 TI - Surgical site infection after pediatric spinal deformity surgery. AB - The incidence of surgical site infection (SSI) after spinal deformity surgery for adolescent idiopathic scoliosis ranges from 0.5-6.7%. The risk of infection following spinal fusion in patients with neuromuscular scoliosis is greater, with reported rates of 6.1-15.2% for cerebral palsy and 8-41.7% for myelodysplasia. SSIs result in increased patient morbidity, multiple operations, prolonged hospital stays, and significant financial costs. Recent literature has focused on elucidating the most common organisms involved in SSIs, as well as identifying modifiable risk factors and prevention strategies that may decrease the rates of infection. These include malnutrition, positive urine cultures, antibiotic prophylaxis, surgical site antisepsis, antibiotic-loaded allograft, local application of antibiotics, and irrigation solutions. Acute and delayed SSIs are managed differently. Removal of instrumentation is required for effective treatment of delayed SSIs. This review article examines the current literature on the prevention and management of SSIs after pediatric spinal deformity surgery. PMID- 22315162 TI - Management of pediatric diaphyseal femur fractures. AB - A variety of strategies are utilized for management of pediatric diaphyseal femur fractures, depending chiefly on the age of the patient. Other factors that can influence the selection of a technique-which range from skeletal traction with spica casting to immediate spica casting, flexible intramedullary nailing, rigid intramedullary rodding, or plate fixation-are weight, fracture severity, associated injuries, and underlying medical or musculoskeletal conditions. The available evidence regarding technique, outcomes, and complications of the aforementioned treatment options remains largely insufficient, and, at times, conflicting, which contributes to the challenges in management decisions. Considerable controversy has arisen over several topics, particularly the optimal treatment for patients aged 5 to 12 years and accepted standards of treatment. This review is designed to provide perspective for some of the most recent influential literature on pediatric diaphyseal femur fracture treatment in light of established evidence and evolving controversies. PMID- 22315163 TI - Transcranial magnetic stimulation reduces nociceptive threshold in rats. AB - Transcranial magnetic stimulation (TMS) is a procedure that uses magnetic fields to stimulate or inhibit nerve cells in the brain noninvasively. TMS induces an electromagnetic current in the underlying cortical neurons. Varying frequencies and intensities of TMS increase or decrease excitability in the cortical area directly targeted. It has been suggested that TMS has potential in the treatment of some neurological disorders such as Parkinson's disease, stroke, and depression. Initial case reports and open label trials reported by several groups support the use of TMS in pain treatment. In the present study, we evaluated the effect of TMS on the nociceptive threshold in the rat. The parameters used were a frequency of 60 Hz and an intensity of 2 and 6 mT for 2 hr twice per day. After 5 days of TMS treatment, rats were evaluated for mechanical, chemical, and cold stimulation. We observed a significant reduction in the nociceptive threshold in TMS-treated rats but not in sham-treated rats in all behavioral tests evaluated. When TMS treatment was stopped, a slow recovery to normal mechanic threshold was observed. Interestingly, i.c.v. MK-801 or CNQX administration reverted the TMS induced pronociception. The results suggest that high-frequency TMS can alter the nociceptive threshold and produce allodynia in the rats; results suggest the involvement of NMDA and AMPA/KA receptors on TMS-induced allodynia in the rat. PMID- 22315164 TI - Matching mice to malignancy: molecular subgroups and models of medulloblastoma. AB - INTRODUCTION: Medulloblastoma, the largest group of embryonal brain tumors, has historically been classified into five variants based on histopathology. More recently, epigenetic and transcriptional analyses of primary tumors have subclassified medulloblastoma into four to six subgroups, most of which are incongruous with histopathological classification. DISCUSSION: Improved stratification is required for prognosis and development of targeted treatment strategies, to maximize cure and minimize adverse effects. Several mouse models of medulloblastoma have contributed both to an improved understanding of progression and to developmental therapeutics. In this review, we summarize the classification of human medulloblastoma subtypes based on histopathology and molecular features. We describe existing genetically engineered mouse models, compare these to human disease, and discuss the utility of mouse models for developmental therapeutics. Just as accurate knowledge of the correct molecular subtype of medulloblastoma is critical to the development of targeted therapy in patients, we propose that accurate modeling of each subtype of medulloblastoma in mice will be necessary for preclinical evaluation and optimization of those targeted therapies. PMID- 22315165 TI - Exfoliation and reassembly of cobalt oxide nanosheets into a reversible lithium ion battery cathode. AB - An exfoliation-reassembly-activation (ERA) approach to lithium-ion battery cathode fabrication is introduced, demonstrating that inactive HCoO(2) powder can be converted into a reversible Li(1-x) H(x) CoO(2) thin-film cathode. This strategy circumvents the inherent difficulties often associated with the powder processing of the layered solids typically employed as cathode materials. The delamination of HCoO(2) via a combination of chemical and mechanical exfoliation generates a highly processable aqueous dispersion of [CoO(2) ](-) nanosheets that is critical to the ERA approach. Following vacuum-assisted self-assembly to yield a thin-film cathode and ion exchange to activate this material, the generated cathodes exhibit excellent cyclability and discharge capacities approaching that of low-temperature-prepared LiCoO(2) (~83 mAh g(-1) ), with this good electrochemical performance attributable to the high degree of order in the reassembled cathode. PMID- 22315166 TI - Statins: have we found the Holy Grail? AB - In coronary artery disease, cardiovascular risk factors are the main targets for primary and secondary prevention. Statins prevent cardiovascular events in patients at risk. However, despite the proven efficacy and safety of statins, relevant side effects exist and should be considered when treating patients. PMID- 22315167 TI - Glial responses after chorda tympani nerve injury. AB - The chorda tympani (CT) nerve innervates lingual taste buds and is susceptible to damage during dental and inner ear procedures. Interruption of the CT results in a disappearance of taste buds, which can be accompanied by taste disturbances. Because the CT usually regenerates to reinnervate taste buds successfully within a few weeks, a persistence of taste disturbances may indicate alterations in central nervous function. Peripheral injury to other sensory nerves leads to glial responses at central terminals, which actively contribute to abnormal sensations arising from nerve damage. Therefore, the current study examined microglial and astrocytic responses in the first central gustatory relay, the nucleus of the solitary tract (nTS), after transection of the CT. Damage to the CT resulted in significant microglial responses in terms of morphological reactivity and an increased density of microglial cells from 2 to 20 days after injury. This increased microglial population resulted primarily from microglial proliferation from 1.5 to 3 days, which was supplemented by microglial migration within subdivisions of the nTS between days 2 and 3. Unlike other nerve injuries, CT injury did not result in recruitment of bone marrow-derived precursors. Astrocytes also reacted in the nTS with increased levels of glial fibrillary acidic protein (GFAP) by 3 days, although none showed evidence of cell division. GFAP levels remained increased at 30 days, by which time microglial responses had resolved. These results show that nerve damage to the CT results in central glial responses, which may participate in long-lasting taste alterations following CT lesion. PMID- 22315168 TI - Depression is associated with some patient-perceived cosmetic changes, but not with radiotherapy-induced late toxicity, in long-term breast cancer survivors. AB - OBJECTIVE: Although depression is prevalent in long-term breast cancer survivors (LTBCS; >= 5 years since diagnosis), it is underdiagnosed and undertreated. A better understanding of factors associated with depression could improve depression screening, treatment, and prevention in this population. Our study aimed to assess the link between patient and doctor ratings of breast cosmetic outcomes, late radiotherapy toxicity, and depression in LTBCS. METHODS: In all, 214 patients recruited from the ARCOSEIN study were assessed for late radiotherapy toxicity (by using the LENT-SOMA scale) and patient and doctor ratings of breast cosmetic outcomes (mean = 6.7 years since the end of treatment). We reassessed 120 of these patients for depression (HAD) during a second wave of long-term assessment (mean = 8.1 years since the end of treatment). We used univariate analyses and polytomous logistic regression analyses to predict the HAD depression, which was defined as follows: normal, 0-7 points; and significant depression, >= 8 points (8-10 points, possible depression; >= 11 points, probable depression). RESULTS: The mean HAD depression score was 4.5 +/- 3.6. 19. 2% of our population had significant depression, 6.7% with probable depression, and 12.5% with possible depression. Significant depression was not associated with late radiotherapy toxicity or initial cancer related variables. Patients with probable depression reported worse cosmetic outcomes than nondepressed patients in terms of perceived breast largeness (p = 0.04), breast deformation (p = 0.02), and changes in skin pigmentation (p = 0.03). CONCLUSIONS: In LTBCS, depression seems to be more strongly associated with changes in some patients' perceived breast cosmetic outcome than late treatment toxicity or initial cancer-related variables. PMID- 22315169 TI - Involvement of ryanodine receptors in tetanic sciatic stimulation-induced long term potentiation of spinal dorsal horn and persistent pain in rats. AB - Tetanic stimulation of the sciatic nerve induces long-term potentiation (LTP) of C-fiber-evoked field potentials in the spinal dorsal horn and persistent pain, suggesting that spinal LTP may be a substrate for central sensitization of the pain pathway. However, its cellular mechanism remains unclear. The present study provides electrophysiological and behavioral evidence for the involvement of ryanodine receptor (RyR) in the induction of spinal LTP and persistent pain in rats. The specific inhibitor of ryanodine receptor, ryanodine and dantrolene, dose dependently blocked the induction, but not maintenance, of spinal LTP and reduced persistent pain behaviors induced by tetanic sciatic stimulation. Both cyclic ADP ribose (cADPR), an endogenous agonist of RyR, and (+/-)-1,4-dihydro 2,6-dimethyl-5-nitro-4-[2-(trifluromethyl)-phenyl]-3-pyridine carboxylic acid methyl ester (Bay K 8644), an agonist of L-type calcium channel, attenuated ryanodine-induced inhibition. Immunohistochemistry and electron microscopic observation showed that RyR subtypes RyR1 and RyR3 were located in the spinal dorsal horn. The results suggest that RyRs are involved in synaptic plasticity of the spinal pain pathway and may be a novel target for treating pain. (c) 2012 Wiley Periodicals, Inc. PMID- 22315170 TI - The microenvironment in the Hirschsprung's disease gut supports myenteric plexus growth. AB - INTRODUCTION: The transplantation of neural crest derived stem cells (NCSC) is a potent alternative for the treatment of Hirschsprung's disease (HSCR). Cells to be transplanted should find an appropriate microenvironment to survive and differentiate. Influences of HSCR-smooth-muscle-protein extracts upon isolated myenteric plexus cells, dissociated dorsal root ganglia and NCSC were studied in vitro to investigate the quality of this microenvironment effects. METHODS: Postnatal human gut from children undergoing colonic resection due to HSCR was divided in segments. Smooth muscle was dissected and homogenized. Glial-cell-line derived-neurotrophic-factor (GDNF) and transforming-growth-factor-beta-1 (TGFbeta 1) concentration were measured in the homogenates from the individual segment using ELISA. Myenteric plexus and dissociated dorsal root ganglia (DRG) cultures, as well as NCSCs were exposed to protein extracts derived from ganglionic and aganglionic HSCR segments, and their effect upon neurite outgrowth, survival, and branching was evaluated. RESULTS AND CONCLUSIONS: The amount of the factors varied considerably between the individual segments and also from patient to patient. Four major expression patterns could be detected. While all extracts tested lead to a significant increase in neurite outgrowth compared to the control, extracts from proximal segments tended to have more prominent effects. In one experiment, extracts from all individual segments of a single patient were tested. Neurite outgrowth, neuronal survival, and branching pattern varied from segment to segment, but all HSCR-muscle-protein extracts increased neuronal survival and network formation. Smooth muscle protein from aganglionic bowel supports the survival and outgrowth of myenteric neurons and NCSCs and is so an appropriate target for neural stem cell treatment. PMID- 22315171 TI - Correlation of aberrant expression of CD133 with FHIT and malignant phenotype of colorectal adenocarcinoma. AB - BACKGROUND: The relationship between the expression of CD133 and fragile histidine triad (FHIT) or prognosis in Chinese colorectal adenocarcinoma is unknown and needs to be explored. MATERIAL AND METHODS: The samples of colorectal adenocarcinoma from 200 Chinese patients with follow-up were analyzed for the expression of CD133 and FHIT proteins by immunohistochemical method. RESULTS: CD133 was highly expressed in up to 42.0%(84/200) of this group of colorectal adenocarcinomas. The expression of CD133 was significantly higher in carcinoma than in normal (P=0.0001) and in adenomatous mucosas (P=0.004). CD133 positively corresponds to histological grade, clinical stage, regional lymphatic metastasis, and distant metastasis (all P<0.05). The mean overall survival time was shorter in patients with CD133 high expression than in those with CD133 low expression (P00.0001). The expression of CD133 was inversely correlative with that of FHIT (r=-0.464, P=0.0001) in colorectal adenocarcinoma. CD133 was an independent prognostic factor (P=0.0001). CONCLUSIONS: The expression of CD133 may be inversely correlated with the expression of FHIT. It is suggested that CD133 may play an important role in the evolution of colorectal adenocarcinoma and be considered as a potential marker for the prognosis. PMID- 22315172 TI - Sleep in patients with epilepsy. PMID- 22315173 TI - The clinical relevance of fetal variant of the circle of Willis and its influence on the cerebral collateral circulation. AB - In a fetal variation of circle of Willis (CoW) there is an embryological defect of the primary collateral circulation. Besides the fact that collateral flow cannot develop between anterior and posterior circulation, the tentorium namely prevents cerebellar vessels from connecting to the supra-tentorium territory. Therefore patients with a fetal variation of circle of Willis could be more prone to develop vascular insufficiency. An association between the regional cerebral blood volume (rCBV) inter-hemispheric asymmetry and CoW collateralization was observed with a topographic significance of corona radiate rather than centrum semiovale. An overview of the literature is given. We propose a fetal variation of circle of Willis as a risk factor for stroke should be subject of further investigation. PMID- 22315174 TI - Ile/Ile homozygosity at codon 655 of HER2 in schwannoma. AB - PURPOSE: This study aimed to determine the genetic role of HER2, one of the epidermal growth factor receptor (EGFR) family, in schwannoma. The latter is a neogrowth of myelin-producing Schwann cells in peripheral nerves, inducible by N nitrosoethylurea in animals with mutation in the neu gene (homologous gene of human HER2 protein). METHODS: In this study we obtained genomic DNA samples from tissue blocks of schwannoma, initially by xylene treatment and alcohol extraction, followed by use of the DNA extraction kit. Evaluation of this genetic polymorphism in our subjects was conducted by direct nucleotide sequencing or restriction enzyme analyses after PCR work. RESULTS: There were thirty extracted DNA samples from tissue blocks of schwannoma, and all were Ile/Ile homozygotes after genotype analyses. Two individuals received the leukocyte DNA extraction after peripheral blood sampling, both showing Ile/Ile homozygosity. This study gave the impression of an association of the HER2 polymorphism at codon 655 with tumorigenesis of schwannoma. Although the majority of the Taiwanese showed Ile/Ile homozygosity (about 83%), the present study revealed a 100% carriage rate among the tissue blocks from our subjects with schwannoma. CONCLUSION: Ile/Ile homozygosity at codon 655 of HER2 in schwannoma may imply some role in tumorigenesis of Ile655Val allele of HER2 in this nerve tumor. PMID- 22315175 TI - Sleep quality and daytime sleepiness in patients with epilepsy. AB - PURPOSE: Poor sleep quality and excessive daytime sleepiness (EDS) are common complaints of patients with epilepsy (PWE). This study aimed to evaluate possible predisposing factors for EDS and subjective sleep quality in PWE. METHODS: One hundred and seventeen PWE were enrolled and 30 healthy volunteers were recruited as controls. EDS was evaluated by the Epworth Sleepiness Scale (ESS) while the Pittsburg Sleep Quality Index (PSQI) was designed to evaluate overall sleep quality. Clinical baseline data and possible risk factors for sleep disturbances were included in the statistical analysis. RESULTS: Twenty percent of PWE (23/117) and 7% of healthy controls (2/30) had excessive daytime sleepiness (p = 0.007). PWE had significantly higher PSQI total scores (6.5 +/- 3.8 vs. 3.7 +/- 2.9), sleep latency (1.2 +/- 0.8 vs. 0.6 +/- 0.7) and sleep efficiency (0.8 +/- 1.0 vs. 0.0 +/- 0.2) scores than the controls (all p < 0.001). A significantly higher prevalence of poor sleep quality was found in the partial seizure, non seizure-free, and polytherapy groups (all p < 0.05). Multivariate analysis showed that poor seizure control was the strongest independent risk factor for poor sleep quality (OR = 2.43, 95% CI = 1.15-5.15, p = 0.02). CONCLUSION: EDS and poor sleep quality are common in PWE and are closely related to partial epilepsy, poor seizure control, and polytherapy. These relationships must be addressed in order to provide the best management of sleep disturbance in such patients. PMID- 22315176 TI - A rare cause of cerebellar ataxia syndrome: superficial siderosis of central nervous system. AB - PURPOSE: To describe and emphasize importance of recognizing superficial siderosis (SS) of the central nervous system (CNS) when assessing cerebellar ataxia syndrome CASE REPORT: Superficial siderosis (SS) of the central nervous system (CNS) is a rare disorder that results from chronic hemosiderin deposition in the subpial layers of the brain and the spinal cord. Although recurrent bleeding in the subarachnoid space is the most likely explanation, a definite history of subarachnoid hemorrhage (SAH) is often lacking. Among the clinical presentations described in the literature include sensorineural deafness, dementia, anosmia, pyramidal tract signs and cerebellar ataxia. However, due to its rarity, SS remains one of the least considered differential diagnosis in patients with sporadic ataxia syndrome. We describe a case of progressive gait imbalance that was initially misdiagnosed for several years until a brain MRI study showed evidence of diffuse hemosiderin deposition suggestive of SS of CNS. CONCLUSION: MR brain with gradient-echo T2-weightd images should be included in all MR studies carried out to investigate the etiology of cerebellar ataxia to allow early diagnosis and prompt intervention for SS. PMID- 22315177 TI - Leukoencephalopathy after levamisole for the treatment of verrucae. AB - PURPOSE: Levamisole is an antihelmintic and immunomodulator used as a dewormer and in combination with other forms of chemotherapy to treat colon cancer, melanoma, and head and neck cancer. It has also been used for treating dermatologic disorders such as verrucae. However, its benefits remain controversial and serious side effects such as central nervous system toxicity are unexpected. CASE REPORT: Multifocal leukoencephalopathy developed in a 26 year-old man after levamisole treatment for verrucae. He recovered completely after discontinuation of the offending drug and treatment with steroid and plasmapheresis. CONCLUSION: Clinicians should be aware of this neurotoxicity in order to provide early diagnosis and treatment and thereby improve outcome. PMID- 22315178 TI - Autologous heparinized oxygenated blood reperfusion in acute ischemic stroke caused by infective endocarditis: a case report. AB - PURPOSE: Cerebral infarction secondary to septic embolism is a lethal complication of infective endocarditis. However, its effective treatment has not been well defined in the previous literature. CASE REPORT: We presented a patient suffering from right middle cerebral artery (MCA) embolism with left hemiplegia and infective endocarditis, who was once treated with intra-arterial thrombolysis with autologous heparinized arterial blood successfully. The patient recovered well with muscle power improvement significantly, but was attacked by another septic embolization with mycotic aneurysm rupture of left side MCA and intracranial hemorrhage. Despite of emergent decompressive craniectomy the patient died of this complication on the 25th day of his hospitalization. CONCLUSION: In this case, we demonstrated the safety and effectiveness of the autologous heparinized arterial blood in recanalization of the occluded vessel. PMID- 22315179 TI - Spontaneous intracranial hypotension with cerebrospinal fluid leakage at 2 sites treated by epidural blood patch. AB - PURPOSE: Spontaneous intracranial hypotension (SIH) is a relatively uncommon cause of headache, which usually presents as orthostatic cranial pain and is relieved by recumbency. The precise cause of spontaneous spinal cerebrospinal fluid leakage related SIH remains unknown. CASE REPORT: We report the case of a 32-year-old man who presented with an orthostatic headache. Brain magnetic resonance imaging (MRI) revealed typical pachymeningeal enhancement. Radionuclide cisternography revealed leakages in the cervicothoracic and upper cervical areas. The patient was successfully treated by lumbar epidural blood patch (EBP). CONCLUSION: The diagnosis of SIH involves the assessment of the characteristic clinical presentations and non-invesive neuroimaging studies. The latest diagnostic criteria with more broadened spectrum due to variable manifestations are discussed. EBP is an effective treatment for SIH if conservative management fails. PMID- 22315180 TI - Ortner's Syndrome. PMID- 22315181 TI - Morphologic evidence for spatially clustered spines in apical dendrites of monkey neocortical pyramidal cells. AB - The general organization of neocortical connectivity in rhesus monkey is relatively well understood. However, mounting evidence points to an organizing principle that involves clustered synapses at the level of individual dendrites. Several synaptic plasticity studies have reported cooperative interaction between neighboring synapses on a given dendritic branch, which may potentially induce synapse clusters. Additionally, theoretical models have predicted that such cooperativity is advantageous, in that it greatly enhances a neuron's computational repertoire. However, largely because of the lack of sufficient morphologic data, the existence of clustered synapses in neurons on a global scale has never been established. The majority of excitatory synapses are found within dendritic spines. In this study, we demonstrate that spine clusters do exist on pyramidal neurons by analyzing the three-dimensional locations of ~40,000 spines on 280 apical dendritic branches in layer III of the rhesus monkey prefrontal cortex. By using clustering algorithms and Monte Carlo simulations, we quantify the probability that the observed extent of clustering does not occur randomly. This provides a measure that tests for spine clustering on a global scale, whenever high-resolution morphologic data are available. Here we demonstrate that spine clusters occur significantly more frequently than expected by pure chance and that spine clustering is concentrated in apical terminal branches. These findings indicate that spine clustering is driven by systematic biological processes. We also found that mushroom-shaped and stubby spines are predominant in clusters on dendritic segments that display prolific clustering, independently supporting a causal link between spine morphology and synaptic clustering. PMID- 22315182 TI - Understanding the basic mechanisms underlying seizures in mesial temporal lobe epilepsy and possible therapeutic targets: a review. AB - Despite years of research, epilepsy remains a poorly understood disorder. In the past several years, work has been conducted on a variety of projects with the goal of better understanding the pathogenesis and progression of mesial temporal lobe epilepsy (MTLE), in particular, and how to exploit those properties to generate innovative therapies for treatment of refractory epilepsies. This review seeks to give an overview of common morphological and biochemical changes associated with epilepsy and proposed treatments to address those changes. Furthering the understanding of ictogenesis and epileptogenesis remains an important goal for scientists seeking to find more effective treatments for MTLE. PMID- 22315183 TI - Long-term psychological distress in women at risk for hereditary breast cancer adhering to regular surveillance: a risk profile. AB - BACKGROUND: Some women at risk for hereditary breast cancer are at increased risk of psychological distress. In order to tailor support for individual women, the availability of a tool enabling the identification of psychologically vulnerable women at an early stage is warranted. The objectives of this study were (1) to explore long-term psychological distress in women at risk for hereditary breast cancer adhering to regular surveillance, and (2) to identify women being vulnerable for long-term psychological distress, defined in terms of a multifactorial risk profile. METHODS: General distress and cancer-related distress were assessed at baseline (T0) and after 5-8 years (T1) in 197 high-risk women adhering to breast cancer surveillance. Coping styles, occurrence of breast cancer in the family of origin, breast cancer risk perception, and frequency of breast self-examination, as assessed at T0, were examined as predictor variables for long-term distress (T1). RESULTS: Across time, women reported a significant reduction in intrusion and avoidance. Intrusion levels were increased among women who had lost a first-degree relative to breast cancer. Predictors of increased long-term distress were passive and palliative coping styles, excessive breast self-examination, and overestimation of breast cancer risk. On the other hand, coping through fostering reassuring thoughts was predictive for decreased long term distress. CONCLUSION: On the basis of the identified risk profile, it is possible to identify vulnerable women at an early stage, who then may be offered additional and individually tailored support. PMID- 22315184 TI - Highly dispersed platinum nanoparticles on TiO2 prepared by using the microwave assisted deposition method: an efficient photocatalyst for the formation of H2 and N2 from aqueous NH3. AB - A simple and practical technique to synthesize nanosized platinum particles loaded on TiO(2) (Pt-TiO(2)) by using a microwave (Mw)-assisted deposition method has been exploited in the development of a highly efficient photocatalyst for the formation of H(2) and N(2) gases from harmful nitrogen-containing chemical wastes, for example, aqueous ammonia (NH(3)). Upon Mw irradiation, a platinum precursor can be deposited quickly on the TiO(2) surface from an aqueous solution of platinum and subsequent reduction with H(2) affords the nanosized platinum metal particles with a narrow size distribution (Mw-Pt-TiO(2)). Characterization by CO adsorption, platinum L(III)-edge X-ray absorption fine structure analysis, and TEM analysis revealed that the size of the metal nanoparticles strongly depended on the preparation methods. Smaller platinum nanoparticles were obtained by the Mw heating method than those obtained by conventional preparation techniques, such as photoassisted deposition (PAD), impregnation (Imp), and equilibrium adsorption (EA) deposition by conventional convective heating. The H(2) and N(2) formation rates increased with increasing dispersity of platinum. Pt-TiO(2) prepared by the Mw heating method exhibited a specifically high H(2) formation activity in the photocatalytic decomposition of aqueous NH(3) in a nearly stoichiometric 3:1 (H(2)/N(2)) molar ratio under inert conditions. The present Mw heating method is applicable to a variety of anatase-type TiO(2) species possessing different specific surface areas to provide small and highly dispersed platinum nanoparticles with a narrow size distribution. PMID- 22315185 TI - Unusual ribbon-like periventricular heterotopia with congenital cataracts in a Japanese girl. AB - Periventricular heterotopia (PH), clumps of neurons mislocated beside the ventricle, is caused by failure to initiate migration during embryogenesis. We report on a 32-month-old Japanese girl with a unique subtype of PH, namely ribbon like PH. The patient presented with severe psychomotor developmental delay, intractable epilepsy, and congenital cataracts and developed West syndrome phenotype. Brain magnetic resonance imaging revealed a unique undulating form of PH, categorized as ribbon-like PH, and other brain malformations including simplified gyri and dysgenesis of the corpus callosum. There was no evidence of prenatal TORCH infection or associated syndrome. Array-based comparative genomic hybridization revealed no chromosomal rearrangements. Genetic analyses of the FLNA, DCX, ARX, LIS1, and TUBA1A genes showed no mutations. Although little is known about ribbon-like PH, the clinical manifestations in our patient clearly differed from those in other reported patients. PMID- 22315186 TI - Scientific rigour in psycho-oncology trials: why and how to avoid common statistical errors. AB - OBJECTIVE: It is well documented that statistical and methodological flaws are common in much of the health research literature, including psycho-oncology. These can have far-reaching effects, including the publishing of misleading results; the wasting of time, effort, and financial resources; exposure of patients to the potential harms of research and decreased confidence in science and researchers by the public. METHODS: Several of the most common statistical errors and methodological pitfalls that occur in the field of psycho-oncology are discussed, including those that occur at the design, analysis, reporting and conclusion stages. RESULTS: Fourteen topics are briefly discussed, explaining why there is a problem and how to avoid it. These include proper approaches to power, clustering, missing data, categorization of continuous variables, subgroup analyses, multiple comparisons, statistical interactions, confidence intervals and correct interpretation of p-values. Extensive referencing points the reader to more in-depth explanations. CONCLUSIONS: To increase the scientific rigour in psycho-oncology, researchers should involve a biostatistician from the beginning of the study and should commit to continuing education on best practices in the fields of statistics and reporting. PMID- 22315187 TI - Occurrence of acute lymphoblastic leukemia and juvenile myelomonocytic leukemia in a patient with Noonan syndrome carrying the germline PTPN11 mutation p.E139D. AB - Noonan syndrome (NS) is a common autosomal dominant condition characterized by short stature, congenital heart defects, and dysmorphic facial features caused in approximately 50% of cases by missense mutations in the PTPN11 gene. NS patients are predisposed to malignancies including myeloproliferative disorders or leukemias. We report a female NS patient carrying a PTPN11 germline mutation c.417 G > C (p.E139D), who developed in her second year of life an acute lymphoblastic leukemia (ALL) and after remission, she developed at 4 years of age a juvenile myelomonocytic leukemia (JMML). Molecular genetic analysis of lymphoblastic blasts at the time of the ALL diagnosis revealed the germline mutation in a heterozygous state, while in the myelomonocytic blasts occurring with JMML diagnosis, the mutation p.E139D was found in a homozygous state due to a uniparental disomy (UPD). These findings lead to the suggestion that the pathogenesis of ALL and JMML in our patient is due to different mechanisms including somatically acquired secondary chromosomal abnormalities. PMID- 22315188 TI - Pyrene-modified unlocked nucleic acids: synthesis, thermodynamic studies, and fluorescent properties. AB - Two pyrene-modified UNA monomers were synthesized and incorporated into 21-mer DNA oligonucleotides. Melting temperatures and thermodynamic properties of the modified duplexes were measured, and the fluorescence properties of single strands and duplexes containing one or more pyrene-UNA modifications were studied. It was found that incorporation of pyrene-UNA monomers increased duplex stability relative to UNA monomers, and thermodynamic studies revealed significant mismatch discriminative capabilities of the pyrene-UNA modified oligonucleotides. Furthermore, the steady-state fluorescence emission intensities of pyrene-UNA modified oligonucleotides were increased upon hybridization to DNA, which to the best of our knowledge is unprecedented for an acyclic pyrene modification in DNA. Interestingly, pyrene excimer emission was observed for single-stranded oligonucleotides containing three pyrene-UNA modifications, whereas this excimer emission disappeared after hybridization to DNA. In view of both the pyrene monomer and the excimer fluorescence emission, the triply modified oligonucleotides show intriguing properties relating to the development of new DNA/RNA detection tools. PMID- 22315189 TI - Call for change in prenatal counseling for Down syndrome. AB - The American Journal of Medical Genetics Part A is to be congratulated for taking a leadership role by publishing a number of papers challenging the status quo of prenatal counseling for Down syndrome and of care for children and adults with Down syndrome. Parents want to know about the future abilities and potential of their fetus with Down syndrome, not simply negative medical information that may be outdated. Those providing counseling and those providing medical care could benefit from contact with individuals with Down syndrome outside the medical context. It is imperative that each person with Down syndrome be viewed as a unique individual with particular talents. Medical care providers should work with parents to help the child or adult with Down syndrome reach his/her goals. PMID- 22315190 TI - Stereospecific formation of a ternary complex of (S)-alpha,beta-fluoromethylene dATP with DNA pol beta. AB - The influence of water: crystallization of (R/S)-alpha,beta-CHF-dATP with the preorganized pol beta-DNA complex shows that (S)-alpha,beta-CHF-dATP is preferentially bound to the active site with the C=F fluorine proximal to a structural water bound to Asp276. PMID- 22315191 TI - Antagonism of microRNA function in zebrafish embryos by using locked nucleic acid enzymes (LNAzymes). AB - MicroRNAs (miRNAs) have crucial functions in many cellular processes, such as differentiation, proliferation and apoptosis; aberrant expression of miRNAs has been linked to human diseases, including cancer. Tools that allow specific and efficient knockdown of miRNAs would be of immense importance for exploring miRNA function. Zebrafish serves as an excellent vertebrate model system to understand the functions of miRNAs involved in a variety of biological processes. We designed and employed a strategy based on locked nucleic acid enzymes (LNAzymes) for in vivo knockdown of miRNA in zebrafish embryos. We demonstrate that LNAzyme can efficiently knockdown miRNAs with minimal toxicity to the zebrafish embryos. PMID- 22315192 TI - Third case of 8q23.3-q24.13 deletion in a patient with Langer-Giedion syndrome phenotype without TRPS1 gene deletion. AB - Langer-Giedion syndrome (LGS) is a contiguous gene syndrome caused by a hemizygous deletion on chromosome 8q23.3-q24.11 involving TRPS1 and EXT1 genes. We report on a girl with LGS phenotype and a 7.5 Mb interstitial deletion at chromosome 8q23.3-q24.13. Array-comparative genomic hybridization (a-CGH) revealed a deletion encompassing only the EXT1 and not the TRPS1 gene. Even though the deletion of TRPS1 and EXT1 genes is responsible for craniofacial and skeletal features of LGS, there have been previous reports of patients with LGS phenotype and 8q24 deletions leaving the TRPS1 gene intact. To our knowledge, this is the third such case. Our patient differs from previously reported LGS patients without TRPS1 gene deletion in that she has the typical LGS facial dysmorphism and skeletal abnormalities. However, the girl is of normal height and has only a mild developmental delay. Additionally, she has dyslalia and premature adrenarche classified as Tanner stage 3 premature pubarche which have not yet been described as features of LGS. We examine the molecular breakpoints and phenotypes of our patient and previously reported cases. PMID- 22315193 TI - Solid acid-catalyzed cellulose hydrolysis monitored by in situ ATR-IR spectroscopy. AB - The solid acid-catalyzed hydrolysis of cellulose was studied under elevated temperatures and autogenous pressures using in situ ATR-IR spectroscopy. Standards of cellulose and pure reaction products, which include glucose, fructose, hydroxymethylfurfural (HMF), levulinic acid (LA), formic acid, and other compounds, were measured in water under ambient and elevated temperatures. A combination of spectroscopic and HPLC analysis revealed that the cellulose hydrolysis proceeds first through the disruption of the glycosidic linkages of cellulose to form smaller cellulose molecules, which are readily observed by their distinctive C-O vibrational stretches. The continued disruption of the linkages in these oligomers eventually results in the formation and accumulation of monomeric glucose. The solid-acid catalyst accelerated the isomerization of glucose to fructose, which then rapidly reacted under hydrothermal conditions to form degradation products, which included HMF, LA, formic acid, and acetic acid. The formation of these species could be suppressed by decreasing the residence time of glucose in the reactor, reaction temperature, and contact with the metal reactor. The hydrolysis of regenerated cellulose proceeded faster and under milder conditions than microcrystalline cellulose, which resulted in increased glucose yield and selectivity. PMID- 22315194 TI - Phenotypic variability in hyperphosphatasia with seizures and neurologic deficit (Mabry syndrome). AB - Hyperphosphatasia with neurologic deficit (Mabry syndrome) was first described in a single family (OMIM#239300) by Mabry et al. [1970]. Although considered rare at the time, more than 20 individuals with the triad of developmental disability, seizures, and hyperphosphatasia have been identified world-wide. The 1-6 mannosyltransferase 2, phosphatidylinositol glycan V (PIGV) gene has been found to be disrupted in some patients with the additional feature of brachytelephalangy. In the present report we identify three patients compound homozygous for PIGV mutations. Two siblings were found to be compound heterozygotes for c.467G > A and c.494C > A in exon 3 of PIGV (the c.494C > A PIGV variant is novel). A third patient with similar phenotype, was a compound heterozygote for the known c.1022C > A/c.1022C > T (p.Ala341Glu/p.Ala341Val) mutation. This patient was also noted to have lysosomal storage in cultured fibroblasts. In contrast, the fourth patient who had no apparent hand abnormality, was found to be heterozygous for a previously unclassified c.1369C > T mutation in exon 4 of the PIGV gene, resulting in a p.Leu457Phe substitution in the catalytic domain of the enzyme. Unless this variant has a dominant negative effect, however, it seems likely that another GPI biosynthesis gene variant may contribute to the disorder, possibly through digenic inheritance. Since slightly fewer than half of the nine cases presented in this report and our previous report [Thompson et al., 2010] have PIGV mutations, we suggest that other genes critical to GPI anchor biosynthesis are likely to be disrupted in some patients. PMID- 22315195 TI - KlenTaq DNA polymerase adopts unique recognition states when encountering matched, mismatched, and abasic template sites: an NMR study. PMID- 22315196 TI - Synthesis of furfural from xylose, xylan, and biomass using AlCl3.6H2O in biphasic media via xylose isomerization to xylulose. AB - Furfural was prepared in high yields (75 %) from the reaction of xylose in a water-tetrahydrofuran biphasic medium containing AlCl(3).6H2O and NaCl under microwave heating at 140 degrees C. The reaction profile revealed the formation of xylulose as an intermediate en route to the dehydration product (furfural). The reaction under these conditions reached completion in 45 min. The aqueous phase containing AlCl(3).6H(2)O and NaCl could be recycled multiple times (>5) without any loss of activity or selectivity for furfural. Extension of this biphasic reaction system to include xylan as the starting material afforded furfural in 64 % yield. The use of corn stover, pinewood, switchgrass, and poplar gave furfural in 55, 38, 56, and 64 % yield, respectively, at 160 degrees C. Even though AlCl(3).6H(2)O did not affect the conversion of crystalline cellulose, moderate yields of the by-product 5-hydroxymethylfurfural (HMF) were noted. The highest HMF yield of 42 % was obtained from pinewood. The coproduction of HMF and furfural from biomass was attributed to the weakening of the cellulose network in the biomass, as a result of hemicellulose hydrolysis. The multifunctional capacity of AlCl(3).6H(2)O (hemicellulose hydrolysis, xylose isomerization, and xylulose dehydration) in combination with its ease of recyclability make it an attractive candidate/catalyst for the selective synthesis of furfural from various biomass feedstocks. PMID- 22315197 TI - The omega-6 fatty acid linoleic acid is associated with risk of gastroschisis: a novel dietary risk factor. AB - Gastroschisis is a congenital abdominal wall defect, thought by many to represent a disruption in intrauterine blood flow, where there is herniation of abdominal organs. Dietary intake is an important environmental factor that has been implicated in the development of many diseases. Omega-6 polyunsaturated fatty acids (PUFAs) are nutrients that are substrates for eicosanoid and cytokine synthesis and prone to oxidation, and play a role in modulating inflammation, immune function, and vascular system development. This pilot case-control study explored the association of dietary intake of the omega-6 PUFA linoleic acid with risk of gastroschisis. Between 2008 and 2011, we recruited 13 pregnant women in mid-gestation who were referred to the UCSD Prenatal Center for evaluation of an abnormal alpha-fetoprotein (AFP) test and subsequently identified as carrying a baby with gastroschisis. Nine controls were selected from a false positive AFP or from the UCSD prenatal clinic. Maternal dietary intake was collected via repeated food record during the last 20 weeks of gestation. Logistic regression was used to test the association between dietary intake of linoleic acid and odds of gastroschisis. Dietary intake of linoleic acid was associated with increased odds of gastroschisis (OR = 1.72; 95% CI: 1.08, 2.74; P = 0.02). A higher maternal intake of omega-6 PUFAs may increase the risk of having a baby with gastroschisis. The mechanism by which this occurs may be via inflammatory processes and oxidative stress leading to a vascular disruption. More research is needed including studies investigating integrated markers of PUFA status or inflammatory markers. PMID- 22315198 TI - Covalent tagging of phosphorylated peptides by phosphate-specific deoxyribozymes. PMID- 22315200 TI - Amniotic fluid elicits appetitive responses in human newborns: fatty acids and appetitive responses. AB - In humans, maternal cues guide newborns to the maternal breast, and transitional cues may be present in maternal-fetal fluids. The aim of the present study was to determine the consistent presence of sensorial cues in three maternal-fetal fluids--amniotic fluid, colostrum, and milk--and test the ability of these cues to produce appetitive responses in newborns. In the analytical study, gas chromatography-mass spectrometry (GC-MS) detected eight fatty acids consistently present in the amniotic fluid, colostrum, and milk from 12 healthy volunteers, but we do not find a mammalian pheromone, identified in another mammalian species (rabbits), in another 30 volunteers. In the behavioral study, we explored the ability of amniotic fluid or its fatty acids to produce appetitive responses in 19 human newborns <24 hr after birth. Exposure to swabs impregnated with amniotic fluid or an artificial fatty acid mixture produced a longer duration of facial reactions that suggested appetitive (sucking) movements compared with respective vehicles (i.e., propylene glycol or centrifuged amniotic fluid with a low fatty acid content verified by GC-MS). We conclude that the fatty acids contained in amniotic fluid may constitute a transitional sensorial cue that guides newborns to the maternal breast. PMID- 22315201 TI - pH-sensitive capsules as intracellular optical reporters for monitoring lysosomal pH changes upon stimulation. AB - The concept of a long-term sensor for ion changes in the lysosome is presented. The sensor is made by layer-by-layer assembly of oppositely charged polyelectrolytes around ion-sensitive fluorophores, in this case for protons. The sensor is spontaneously incorporated by cells and resides over days in the lysosome. Intracellular changes of the concentration of protons upon cellular stimulation with pH-active agents are monitored by read-out of the sensor fluorescence at real time. With help of this sensor concept it is demonstrated that the different agents used (Monensin, Chloroquine, Bafilomycin A1, Amiloride) possessed different kinetics and mechanisms of action in affecting the intracellular pH values. PMID- 22315202 TI - Array CGH on unstimulated blood does not detect all cases of Pallister-Killian syndrome: a skin biopsy should remain the diagnostic gold standard. AB - A child whose features are consistent with Pallister-Killian syndrome (PKS) did not have detectable tetrasomy 12p due to an additional isochromosome 12p in an unstimulated blood specimen by interphase FISH or array CGH analysis. The diagnosis of PKS was made through these methods solely in a skin biopsy specimen. To determine the sensitivity of our array CGH platform to tetrasomy 12p mosaicism, dilutions of DNA from both the child's skin fibroblasts and a PKS cell line were analyzed. Tetrasomy 12p at 10% mosaicism was identifiable but 5% was below the limit of detection. This result suggests through extrapolation that the tetrasomy 12p is present in <10% of cells in our patient's blood, confirming the tissue-limited mosaicism of PKS. Multiple recent studies show that array CGH provides greater sensitivity than chromosome analysis to detect mosaic abnormalities including that of tetrasomy 12p in blood specimens. However, our case demonstrates that the biology of PKS precludes the exclusive use of array CGH on blood for diagnosis. A tissue sample should continue to be the diagnostic gold standard for PKS. PMID- 22315203 TI - Use and non-use of genetic counseling after diagnosis of a birth defect. AB - We examined factors and experiences associated with parents' use or non-use of genetic counseling services within 5 years of the diagnosis of a birth defect in their child. Eligible parents were identified using birth defects data for births in 2004 in Victoria, Australia, and invited to complete a written questionnaire and optional telephone interview. Participants were asked about sources of genetic information, experiences and satisfaction with obtaining this information, and impressions of genetic services. Reasons given for not attending genetic counseling services included not knowing the service was available, or not feeling a need to attend. Non-users commonly stated they would not consider termination of pregnancy for the type of birth defect experienced or that they obtained information from other sources, such as pediatricians. This study indicates that parents, whose child has been diagnosed with a birth defect, could benefit from being informed about available genetic counseling services. The results show that some non-users of genetics services may have misconceptions about the purpose of genetic counseling and correcting these may increase utilization. This is important in order to ensure all parents receive sufficient information and support after diagnosis of a birth defect in their child. PMID- 22315204 TI - Hierarchical structural nanopore arrays fabricated by pre-patterning aluminum using nanosphere lithography. AB - A highly ordered and hierarchical structural nanopore array is fabricated via anodizing a pre-patterned aluminum foil under an optimized voltage. A pre patterned hexagonal nanoindentation array on an aluminum substrate is prepared via the nanosphere lithography method. This pattern leads to an elaborate nanochannel structure with seven nanopores in each nanoindentation after anodization treatment. The structure achieved in our study is new, interesting, and likely to be applied in photonic devices. PMID- 22315205 TI - Psychometric properties of the Swedish Rheumatic Disease Empowerment Scale, SWE RES-23. AB - INTRODUCTION: Empowerment is a central concept in both rheumatology and diabetes care. A Swedish empowerment instrument for patients with rheumatic diseases has not been created before now. The aim of the present study was to determine the psychometric properties of the Swedish Rheumatic Disease Empowerment Scale, SWE RES-23, such as construct validity, internal consistency reliability, inter-item correlations and discriminant validity. METHODS: The already existing instrument, the Swedish Diabetes Empowerment Scale (SWE-DES-23), was adapted for use in patients with rheumatic diseases. The adapted instrument was called the SWE-RES 23. In 2009, 260 patients with rheumatic diseases from a rheumatology unit in Sweden completed the instrument. Construct validity was tested by using exploratory factor analysis. Internal consistency reliability was tested by the use of Cronbach's alpha-coefficient. In order to determine unidimensionality of the empowerment subscales, inter-item correlations were calculated. To establish discriminant validity, an item about self-perceived health from the Short Form (SF) 36 was used in addition to the SWE-RES-23. RESULTS: The exploratory factor analysis resulted in five factors (empowerment subscales) with eigenvalues >1, explaining 64.1% of the total variance: Goal achievement and overcoming barriers to goal achievement; Self-knowledge; Managing stress; Assessing dissatisfaction and readiness to change; and Support for caring. Cronbach's alpha values ranged from 0.59 to 0.91, and the value for the total score was 0.92. CONCLUSION: The results support the possibility of adapting the SWE-DES-23 for use in patients with rheumatic diseases. The SWE-RES-23 shows acceptable psychometric properties, in terms of construct validity and internal consistency reliability. To validate the SWE-RES-23 fully, further studies are needed, with a focus on test-retest correlations. PMID- 22315206 TI - Further characterization of Shwachman-Diamond syndrome: psychological functioning and quality of life in adult and young patients. AB - To assess psychosocial functioning and quality of life in a representative group of adult and young patients with Shwachman-Diamond syndrome (SDS), all patients 3 years old and over included in the Italian SDS Registry were investigated using an ad-hoc questionnaire for information about demography, education, socialization, rehabilitation therapy, and standardized questionnaires [SF-36, Child Behavior Check-List (CBCL)] for quality of life and behavior. Results were compared with those of a Cystic Fibrosis (CF) patient group, matched for age and sex. Eighty-one percent of patients answered. All but one adult patient lived with their parents, 24% had independent income, and 57% had a driver's license. Different levels (from mild to severe) of cognitive impairment were reported by 76% of the adults and by 65% of the young patients. These data are significantly lower than those of the CF group. Both groups present low scores in the emotional and mental health evaluations at SF-36, but SDS patients reported significantly more limitations in physical functioning (PF) and more body pain (BP) experiences. As reported by parents at CBCL, young SDS patients show more "social problems" (in the clinical area 31% SDS vs. 6% CF), "attention deficits disorder" (29% SDS vs. 0%CF), and "somatic complaints" (24% SDS vs. 12% CF). Psychosocial functioning is impaired in the majority of SDS patients, significantly more than in patients affected by CF. PMID- 22315207 TI - Resource implications of expanding the use of donation after circulatory determination of death in liver transplantation. AB - In the United Kingdom, liver transplantation using donation after circulatory determination of death (DCDD) organs has increased steadily over the last few years and now accounts for 20% of UK transplant activity. The procurement of DCDD livers is actively promoted as a means of increasing the donor pool and bridging the evolving disparity between the wait-list length and the number of transplants performed. The objective of this retrospective study of a cohort of patients who were matched for age, liver disease etiology, and Model for End-Stage Liver Disease score was to determine whether differences in perioperative costs and resource utilization are associated with the use of such organs. Our results showed an increased prevalence of reperfusion syndrome in the DCDD cohort (P < 0.001), a prolonged heparin effect (P = 0.01), a greater incidence of hyperfibrinolysis (P = 0.002), longer periods of postoperative ventilator use (P = 0.03) and vasopressor support (P = 0.002), and a prolonged length of stay in the intensive therapy unit (ITU; P = 0.02). The peak posttransplant aspartate aminotransferase level was higher in the DCDD group (P = 0.007), and there was significantly more graft failure at 12 months (P = 0.03). In conclusion, we have demonstrated different perioperative and early postoperative courses for DCDD and donation after brain death (DBD) liver transplants. The overall quality of DCDD grafts is poorer; as a result, the length of the ITU stay and the need for multiorgan support are increased, and this has significant financial and resource implications. We believe that these implications require a careful real-life consideration of benefits. It is essential for DCDD not to be seen as a like-for like alternative to DBD and for every effort to be continued to be made to increase the number of donations from brain-dead patients as a first resort. PMID- 22315208 TI - A de novo 14q12q13.3 interstitial deletion in a patient affected by a severe neurodevelopmental disorder of unknown origin. PMID- 22315209 TI - Ex vivo measurement reliability using two different cbct scanners for orthodontic purposes. AB - BACKGROUND: There are many cone beam computed tomography (CBCT) scanners available on the market: detector technology, algorithm precision, and scanner settings influence image quality. The aim of this study was to compare the accuracy of linear measurements made on images of the same sample obtained using two different CBCT scanners. METHODS: Twenty-eight linear measurements between orthodontic anatomical landmarks that were marked with gutta-percha points on a fresh sacrificed lamb head were taken three times. The head was scanned with two CBCT scanners using different scanning parameters. Digital Imaging and Communications in Medicine (DICOM) images were reconstructed and the same measurements were taken three times by the same operator. Measurements were repeated 4 months later by two operators. RESULTS: There was minimal, clinically significant difference between the measurements taken with the digital caliper or CBCT scanners, but there was no difference between the two different scanners. CONCLUSIONS: There is no clinically significant difference between these two scanners; a difference was found between the CBCT and real anatomical measurements in only a few cases. PMID- 22315210 TI - Treatment with sildenafil and treprostinil allows successful liver transplantation of patients with moderate to severe portopulmonary hypertension. AB - Portopulmonary hypertension (PoPH) refers to pulmonary arterial hypertension associated with portal hypertension with or without evidence of an underlying liver disease. Despite the potential for curing PoPH with liver transplantation, the presence of moderate or severe PoPH is associated with increased morbidity and mortality and is, therefore, a contraindication to transplantation. Previous studies have predominantly used intravenous epoprostenol for treatment in order to qualify patients for liver transplantation. In this retrospective case series, we describe the clinical course of 11 patients whom we successfully treated (predominantly with oral sildenafil and subcutaneous treprostinil) in order to qualify them for liver transplantation. The mean pulmonary artery pressure significantly improved from 44 to 32.9 mm Hg, and the pulmonary vascular resistance decreased from 431 to 173 dyn second cm(-5) . There were significant improvements in the cardiac output and the transpulmonary gradient with these therapies as well. All 11 patients subsequently received liver transplants with a 0% mortality rate to date; the duration of follow-up ranged from 7 to 60 months. After transplantation, 7 of the 11 patients (64%) were off all pulmonary vasodilators, and only 2 patients required transiently increased doses of prostacyclins. In conclusion, an aggressive approach to the treatment of PoPH with sildenafil and/or treprostinil and subsequent liver transplantation may be curative for PoPH in some patients. PMID- 22315211 TI - Complex relationship between meiotic recombination frequency and autosomal synaptonemal complex length per cell in normal human males. AB - Although the relationship between meiotic recombination frequency and synaptonemal complex (SC) length has been of interest for a long time, how recombination frequency is related to SC length has not been carefully explored. To address this question, we have measured the meiotic recombination frequency as represented by MLH1 foci in 889 pachytene spermatocytes and measured the length of 19,558 autosomal SCs from 10 human males. A complex relationship between the number of MLH1 foci and total autosomal SC length per cell was observed. A positive correlation with significant correlation coefficients between the two variables was found in eight of the ten donors examined, with three donors showing weak correlation, and five showing moderate correlation. Two donors who did not show any correlation between the two variables were identified for the first time. Moreover, most cells with similar total autosomal SC length showed very different numbers of MLH1 foci both between individuals and even within an individual, and vice versa. Our data provide the first evidence for a complex relationship between the recombination frequency and total length of autosomal SCs per cell in human males. PMID- 22315212 TI - Immunoprophylaxis against and prevention of recurrent viral hepatitis after liver transplantation. AB - The reinfection of the hepatic allograft with hepatitis B virus and hepatitis C virus can have important sequelae that result in poor long-term patient and graft survival. Although a response to treatment with antiviral medications can improve these outcomes, not all patients tolerate these medications or experience viral eradication. Avoiding reinfection of the graft is the most effective means of improving the long-term outcomes for these patient populations. This review is focused on the prevention of viral hepatitis reinfection after liver transplantation. PMID- 22315213 TI - Inflammation and ankylosis: still an enigmatic relationship in spondyloarthritis. PMID- 22315214 TI - Lip swelling as initial manifestation of Crohn's disease. PMID- 22315215 TI - Investigation of D2 receptor-agonist interactions using a combination of pharmacophore and receptor homology modeling. AB - A combined modeling approach was used to identify structural factors that underlie the structure-activity relationships (SARs) of full dopamine D2 receptor agonists and structurally similar inactive compounds. A 3D structural model of the dopamine D2 receptor was constructed, with the agonist (-)-(R)-2-OH-NPA present in the binding site during the modeling procedure. The 3D model was evaluated and compared with our previously published D2 agonist pharmacophore model. The comparison revealed an inconsistency between the projected hydrogen bonding feature (Ser-TM5) in the pharmacophore model and the TM5 region in the structure model. A new refined pharmacophore model was developed, guided by the shape of the binding site in the receptor model and with less emphasis on TM5 interactions. The combination of receptor and pharmacophore modeling also identified the importance of His3936.55 for agonist binding. This convergent 3D pharmacophore and protein structure modeling strategy is considered to be general and can be highly useful in less well-characterized systems to explore ligand receptor interactions. The strategy has the potential to identify weaknesses in the individual models and thereby provides an opportunity to improve the discriminating predictivity of both pharmacophore searches and structure-based virtual screens. PMID- 22315216 TI - Investigation of D1 receptor-agonist interactions and D1/D2 agonist selectivity using a combination of pharmacophore and receptor homology modeling. AB - The aim of this study was to use a combined structure and pharmacophore modeling approach to extract information regarding dopamine D1 receptor agonism and D1/D2 agonist selectivity. A 3D structure model of the D1 receptor in its agonist-bound state was constructed with a full D1 agonist present in the binding site. Two different binding modes were identified using (+)-doxanthrine or SKF89626 in the modeling procedure. The 3D model was further compared with a selective D1 agonist pharmacophore model. The pharmacophore feature arrangement was found to be in good agreement with the binding site composition of the receptor model, but the excluded volumes did not fully reflect the shape of the agonist binding pocket. A new receptor-based pharmacophore model was developed with forbidden volumes centered on atom positions of amino acids in the binding site. The new pharmacophore model showed a similar ability to discriminate as the previous model. A comparison of the 3D structures and pharmacophore models of D1 and D2 receptors revealed differences in shape and ligand-interacting features that determine selectivity of D1 and D2 receptor agonists. A hydrogen bond pharmacophoric feature (Ser-TM5) was shown to contribute most to the selectivity. Non-conserved residues in the binding pocket that strongly contribute to D1/D2 receptor agonist selectivity were also identified; those were Ser/Cys3.36, Tyr/Phe5.38, Ser/Tyr5.41, and Asn/His6.55 in the transmembrane (TM) helix region, together with Ser/Ile and Leu/Asn in the second extracellular loop (EC2). This work provides useful information for the design of new selective D1 and D2 agonists. The combined receptor structure and pharmacophore modeling approach is considered to be general, and could therefore be applied to other ligand-protein interactions for which experimental information is limited. PMID- 22315217 TI - Kinetics of precursor interactions with the bacterial Tat translocase detected by real-time FRET. AB - The Escherichia coli twin-arginine translocation (Tat) system transports fully folded and assembled proteins across the inner membrane into the periplasmic space. Traditionally, in vitro protein translocation studies have been performed using gel-based transport assays. This technique suffers from low time resolution, and often, an inability to distinguish between different steps in a continuously occurring translocation process. To address these limitations, we have developed an in vitro FRET-based assay that reports on an early step in the Tat translocation process in real-time. The natural Tat substrate pre-SufI was labeled with Alexa532 (donor), and the fluorescent protein mCherry (acceptor) was fused to the C terminus of TatB or TatC. The colored Tat proteins were easily visible during purification, enabling identification of a highly active inverted membrane vesicle (IMV) fraction yielding transport rates with NADH almost an order of magnitude faster than previously reported. When pre-SufI was bound to the translocon, FRET was observed for both Tat proteins. FRET was diminished upon addition of nonfluorescent pre-SufI, indicating that the initial binding step is reversible. When the membranes were energized with NADH, the FRET signal was lost after a short delay. These data suggest a model in which a Tat cargo initially associates with the TatBC complex, and an electric field gradient is required for the cargo to proceed to the next stage of transport. This cargo migration away from the TatBC complex requires a significant fraction of the total transport time. PMID- 22315218 TI - Uroplakins do not restrict CO2 transport through urothelium. AB - Lipid bilayers and biological membranes are freely permeable to CO(2), and yet partial CO(2) pressure in the urine is 3-4-fold higher than in blood. We hypothesized that the responsible permeability barrier to CO(2) resides in the umbrella cell apical membrane of the bladder with its dense array of uroplakin complexes. We found that disrupting the uroplakin layer of the urothelium resulted in water and urea permeabilities (P) that were 7- to 8-fold higher than in wild type mice with intact urothelium. However, these interventions had no impact on bladder P(CO2) (~1.6 * 10(-4) cm/s). To test whether the observed permeability barrier to CO(2) was due to an unstirred layer effect or due to kinetics of CO(2) hydration, we first measured the carbonic anhydrase (CA) activity of the bladder epithelium. Finding none, we reduced the experimental system to an epithelial monolayer, Madin-Darby canine kidney cells. With CA present inside and outside the cells, we showed that P(CO2) was unstirred layer limited (~7 * 10(-3) cm/s). However, in the total absence of CA activity P(CO2) decreased 14-fold (~ 5.1 * 10(-4) cm/s), indicating that now CO(2) transport is limited by the kinetics of CO(2) hydration. Expression of aquaporin-1 did not alter P(CO2) (and thus the limiting transport step), which confirmed the conclusion that in the urinary bladder, low P(CO2) is due to the lack of CA. The observed dependence of P(CO2) on CA activity suggests that the tightness of biological membranes to CO(2) may uniquely be regulated via CA expression. PMID- 22315219 TI - CtBP-interacting BTB zinc finger protein (CIBZ) promotes proliferation and G1/S transition in embryonic stem cells via Nanog. AB - Mouse embryonic stem cells (ESCs) require transcriptional regulation to ensure rapid proliferation that allows for self-renewal. However, the molecular mechanism by which transcriptional factors regulate this rapid proliferation remains largely unknown. Here we present data showing that CIBZ, a BTB domain zinc finger transcriptional factor, is a key transcriptional regulator for regulation of ESC proliferation. Here we show that deletion or siRNA knockdown of CIBZ inhibits ESC proliferation. Cell cycle analysis shows that loss of CIBZ delays the progression of ESCs through the G1 to S phase transition. Conversely, constitutive ectopic expression of exogenous CIBZ in ESCs promotes proliferation and accelerates G1/S transition. These findings suggest that regulation of the G1/S transition explains, in part, CIBZ-associated ESC proliferation. Our data suggest that CIBZ acts through the post-transcriptionally regulates the expression of Nanog, a positive regulator of ESC proliferation and G1/S transition, but does not affect Oct3/4 and Sox2 protein expression. Notably, constitutive overexpression of Nanog partially rescued the proliferation defect caused by CIBZ knockdown, indicating the role of CIBZ in ESC proliferation and G1/S transition at least in part depends on the Nanog protein level. PMID- 22315220 TI - Exposure of mycobacteria to cell wall-inhibitory drugs decreases production of arabinoglycerolipid related to Mycolyl-arabinogalactan-peptidoglycan metabolism. AB - The "cell wall core" consisting of a mycolyl-arabinogalactan-peptidoglycan (mAGP) complex represents the hallmark of the mycobacterial cell envelope. It has been the focus of intense research at both structural and biosynthetic levels during the past few decades. Because it is essential, mAGP is also regarded as a target for several antitubercular drugs. Herein, we demonstrate that exposure of Mycobacterium bovis Bacille Calmette-Guerin or Mycobacterium marinum to thiacetazone, a second line antitubercular drug, is associated with a severe decrease in the level of a major apolar glycolipid. This inhibition requires MmaA4, a methyltransferase reported to participate in the activation process of thiacetazone. Following purification, this glycolipid was subjected to detailed structural analyses, combining gas-liquid chromatography, mass spectrometry, and nuclear magnetic resonance. This allowed to identify it as a 5-O-mycolyl-beta Araf-(1->2)-5-O-mycolyl-alpha-Araf-(1->1)-Gro, designated dimycolyl diarabinoglycerol (DMAG). The presence of DMAG was subsequently confirmed in other slow growing pathogenic species, including Mycobacterium tuberculosis. DMAG production was stimulated in the presence of exogenous glycerol. Interestingly, DMAG appears structurally identical to the terminal portion of the mycolylated arabinosyl motif of mAGP, and the metabolic relationship between these two components was provided using antitubercular drugs such as ethambutol or isoniazid known to inhibit the biosynthesis of arabinogalactan or mycolic acid, respectively. Finally, DMAG was identified in the cell wall of M. tuberculosis. This opens the possibility of a potent biological function for DMAG that may be important to mycobacterial pathogenesis. PMID- 22315221 TI - Modulation of gain-of-function alpha6*-nicotinic acetylcholine receptor by beta3 subunits. AB - We previously have shown that beta3 subunits either eliminate (e.g. for all-human (h) or all-mouse (m) alpha6beta4beta3-nAChR) or potentiate (e.g. for hybrid malpha6hbeta4hbeta3- or malpha6mbeta4hbeta3-nAChR containing subunits from different species) function of alpha6*-nAChR expressed in Xenopus oocytes, and that nAChR halpha6 subunit residues Asn-143 and Met-145 in N-terminal domain loop E are important for dominant-negative effects of nAChR hbeta3 subunits on halpha6*-nAChR function. Here, we tested the hypothesis that these effects of beta3 subunits would be preserved even if nAChR alpha6 subunits harbored gain-of function, leucine- or valine-to-serine mutations at 9' or 13' positions (L9'S or V13'S) in their second transmembrane domains, yielding receptors with heightened functional activity and more amenable to assessment of effects of beta3 subunit incorporation. However, coexpression with beta3 subunits potentiates rather than suppresses function of all-human, all-mouse, or hybrid alpha6((L9'S or V13'S))beta4*- or alpha6(N143D+M145V)(L9'S)beta2*-nAChR. This contrasts with the lack of consistent function when alpha6((L9'S or V13'S)) and beta2 subunits are expressed alone or in the presence of wild-type beta3 subunits. These results provide evidence that gain-of-function halpha6hbeta2*-nAChR (i.e. halpha6(N143D+M145V)(L9'S)hbeta2hbeta3 nAChR) could be produced in vitro. These studies also indicate that nAChR beta3 subunits can be assembly partners in functional alpha6*-nAChR and that 9' or 13' mutations in the nAChR alpha6 subunit second transmembrane domain can act as gain-of-function and/or reporter mutations. Moreover, our findings suggest that beta3 subunit coexpression promotes function of alpha6*-nAChR. PMID- 22315222 TI - Thyroid hormone activates protein arginine methyltransferase 1 expression by directly inducing c-Myc transcription during Xenopus intestinal stem cell development. AB - Adult organ-specific stem cells are essential for organ homeostasis and tissue repair and regeneration. The formation of such stem cells during vertebrate development is poorly understood. Intestinal remodeling during thyroid hormone (T3)-dependent Xenopus metamorphosis resembles postembryonic intestinal maturation in mammals. During metamorphosis, the intestine is remodeled de novo via a yet unknown mechanism. Protein arginine methyltransferase 1 (PRMT1) is up regulated in and required for adult intestinal stem cells during metamorphosis. PRMT1 up-regulation is the earliest known molecular event for the developing stem cells and is also conserved during zebrafish and mouse intestinal development. To analyze how PRMT1 is specifically up-regulated during the formation of the adult intestinal stem cells, we cloned the Xenopus PRMT1 promoter and characterized it in CaCo-2 cells, a human cell line with intestinal stem cell characteristics. Through a series deletion and mutational analyses, we showed that the stem cell associated transcription factor c-Myc could bind to a conserved site in the first intron to activate the promoter. Furthermore, we demonstrated that during metamorphosis, both c-Myc and PRMT1 were highly up-regulated, specifically in the remodeling intestine but not the resorbing tail, and that c-Myc was induced by T3 prior to PRMT1 up-regulation. In addition, we showed that T3 directly activated the c-Myc gene during metamorphosis in the intestine via binding of the T3 receptor to the c-Myc promoter. These results suggest that T3 induces c-Myc transcription directly in the intestine, that c-Myc, in turn, activates PRMT1 expression, and that this is an important gene regulation cascade controlling intestinal stem cell development. PMID- 22315223 TI - Membrane type 1 matrix metalloproteinase (MT1-MMP) ubiquitination at Lys581 increases cellular invasion through type I collagen. AB - Membrane type 1 matrix metalloproteinase (MT1-MMP/MMP14) is a zinc-dependent type I transmembrane metalloproteinase playing pivotal roles in the regulation of pericellular proteolysis and cellular migration. Elevated expression levels of MT1-MMP have been demonstrated to correlate with a poor prognosis in cancer. MT1 MMP has a short intracellular domain (ICD) that has been shown to play important roles in cellular migration and invasion, although these ICD-mediated mechanisms remain poorly understood. In this study, we report that MT1-MMP is mono ubiquitinated at its unique lysine residue (Lys(581)) within the ICD. Our data suggest that this post-translational modification is involved in MT1-MMP trafficking as well as in modulating cellular invasion through type I collagen matrices. By using an MT1-MMP Y573A mutant or the Src family inhibitor PP2, we observed that the previously described Src-dependent MT1-MMP phosphorylation is a prerequisite for ubiquitination. Taken together, these findings show for the first time an additional post-translational modification of MT1-MMP that regulates its trafficking and cellular invasion, which further emphasizes the key role of the MT1-MMP ICD. PMID- 22315225 TI - Distinct domains of paracingulin are involved in its targeting to the actin cytoskeleton and regulation of apical junction assembly. AB - Paracingulin is an M(r) 150-160 kDa cytoplasmic protein of vertebrate epithelial tight and adherens junctions and comprises globular head, coiled-coil rod, and globular tail domains. Unlike its homologous tight junction protein cingulin, paracingulin has been implicated in the control of junction assembly and has been localized at extrajunctional sites in association with actin filaments. Here we analyze the role of paracingulin domains, and specific regions within the head and rod domains, in the function and localization of paracingulin by inducible overexpression of exogenous proteins in epithelial Madin Darby canine kidney (MDCK) cells and by expression of mutated and chimeric constructs in Rat1 fibroblasts and MDCK cells. The overexpression of the rod + tail domains of paracingulin perturbs the development of the tight junction barrier and Rac1 activation during junction assembly by the calcium switch, indicating that regulation of junction assembly by paracingulin is mediated by these domains. Conversely, only constructs containing the head domain target to junctions in MDCK cells and Rat1 fibroblasts. Furthermore, expression of chimeric cingulin and paracingulin constructs in Rat1 fibroblasts and MDCK cells identifies specific sequences within the head and rod domains of paracingulin as critical for targeting to actin filaments and regulation of junction assembly, respectively. In summary, we characterize the functionally important domains of paracingulin that distinguish it from cingulin. PMID- 22315224 TI - Hypermethylated in cancer 1 (HIC1) recruits polycomb repressive complex 2 (PRC2) to a subset of its target genes through interaction with human polycomb-like (hPCL) proteins. AB - HIC1 (hypermethylated in cancer 1) is a tumor suppressor gene epigenetically silenced or deleted in many human cancers. HIC1 is involved in regulatory loops modulating p53- and E2F1-dependent cell survival, growth control, and stress responses. HIC1 is also essential for normal development because Hic1-deficient mice die perinatally and exhibit gross developmental defects throughout the second half of development. HIC1 encodes a transcriptional repressor with five C(2)H(2) zinc fingers mediating sequence-specific DNA binding and two repression domains: an N-terminal BTB/POZ domain and a central region recruiting CtBP and NuRD complexes. By yeast two-hybrid screening, we identified the Polycomb-like protein hPCL3 as a novel co-repressor for HIC1. Using multiple biochemical strategies, we demonstrated that HIC1 interacts with hPCL3 and its paralog PHF1 to form a stable complex with the PRC2 members EZH2, EED, and Suz12. Confirming the implication of HIC1 in Polycomb recruitment, we showed that HIC1 shares some of its target genes with PRC2, including ATOH1. Depletion of HIC1 by siRNA interference leads to a partial displacement of EZH2 from the ATOH1 promoter. Furthermore, in vivo, ATOH1 repression by HIC1 is associated with Polycomb activity during mouse cerebellar development. Thus, our results identify HIC1 as the first transcription factor in mammals able to recruit PRC2 to some target promoters through its interaction with Polycomb-like proteins. PMID- 22315226 TI - The cell surface glycoprotein CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor-mediated cell migration. AB - Epidermal growth factor (EGF) activation of the EGF receptor (EGFR) is an important mediator of cell migration, and aberrant signaling via this system promotes a number of malignancies including ovarian cancer. We have identified the cell surface glycoprotein CDCP1 as a key regulator of EGF/EGFR-induced cell migration. We show that signaling via EGF/EGFR induces migration of ovarian cancer Caov3 and OVCA420 cells with concomitant up-regulation of CDCP1 mRNA and protein. Consistent with a role in cell migration CDCP1 relocates from cell-cell junctions to punctate structures on filopodia after activation of EGFR. Significantly, disruption of CDCP1 either by silencing or the use of a function blocking antibody efficiently reduces EGF/EGFR-induced cell migration of Caov3 and OVCA420 cells. We also show that up-regulation of CDCP1 is inhibited by pharmacological agents blocking ERK but not Src signaling, indicating that the RAS/RAF/MEK/ERK pathway is required downstream of EGF/EGFR to induce increased expression of CDCP1. Our immunohistochemical analysis of benign, primary, and metastatic serous epithelial ovarian tumors demonstrates that CDCP1 is expressed during progression of this cancer. These data highlight a novel role for CDCP1 in EGF/EGFR-induced cell migration and indicate that targeting of CDCP1 may be a rational approach to inhibit progression of cancers driven by EGFR signaling including those resistant to anti-EGFR drugs because of activating mutations in the RAS/RAF/MEK/ERK pathway. PMID- 22315227 TI - alpha-Synuclein in central nervous system and from erythrocytes, mammalian cells, and Escherichia coli exists predominantly as disordered monomer. AB - Since the discovery and isolation of alpha-synuclein (alpha-syn) from human brains, it has been widely accepted that it exists as an intrinsically disordered monomeric protein. Two recent studies suggested that alpha-syn produced in Escherichia coli or isolated from mammalian cells and red blood cells exists predominantly as a tetramer that is rich in alpha-helical structure (Bartels, T., Choi, J. G., and Selkoe, D. J. (2011) Nature 477, 107-110; Wang, W., Perovic, I., Chittuluru, J., Kaganovich, A., Nguyen, L. T. T., Liao, J., Auclair, J. R., Johnson, D., Landeru, A., Simorellis, A. K., Ju, S., Cookson, M. R., Asturias, F. J., Agar, J. N., Webb, B. N., Kang, C., Ringe, D., Petsko, G. A., Pochapsky, T. C., and Hoang, Q. Q. (2011) Proc. Natl. Acad. Sci. 108, 17797-17802). However, it remains unknown whether or not this putative tetramer is the main physiological form of alpha-syn in the brain. In this study, we investigated the oligomeric state of alpha-syn in mouse, rat, and human brains. To assess the conformational and oligomeric state of native alpha-syn in complex mixtures, we generated alpha syn standards of known quaternary structure and conformational properties and compared the behavior of endogenously expressed alpha-syn to these standards using native and denaturing gel electrophoresis techniques, size-exclusion chromatography, and an oligomer-specific ELISA. Our findings demonstrate that both human and rodent alpha-syn expressed in the central nervous system exist predominantly as an unfolded monomer. Similar results were observed when human alpha-syn was expressed in mouse and rat brains as well as mammalian cell lines (HEK293, HeLa, and SH-SY5Y). Furthermore, we show that alpha-syn expressed in E. coli and purified under denaturing or nondenaturing conditions, whether as a free protein or as a fusion construct with GST, is monomeric and adopts a disordered conformation after GST removal. These results do not rule out the possibility that alpha-syn becomes structured upon interaction with other proteins and/or biological membranes. PMID- 22315228 TI - Lack of plakoglobin in epidermis leads to keratoderma. AB - Loss-of-function mutation of Jup has been associated with Naxos disease, which is characterized by arrhythmogenic cardiomyopathy and the cutaneous disorder palmoplantar keratoderma. Previously, we have shown that genetic ablation of Jup in cardiomyocytes in mice leads to arrhythmogenic cardiomyopathy similar to Naxos disease in humans. Currently, to determine the pathogenesis of Naxos disease associated keratoderma, we generated Jup mutant mice by inactivating Jup restrictively in keratinocytes. Jup mutant mice largely recapitulated the clinical features of human palmoplantar keratoderma: overcornification and thickening of the epidermis. Jup mutant mice also suffered skin ulceration and inflammation. Cell apoptosis and proliferation were significantly elevated in Jup mutant epidermis. Ultrastructural analyses revealed the disruption of the assembly of desmosomes and adherens junctions in Jup mutant epidermis. We also demonstrated the compensational increase in beta-catenin at Jup mutant cell-cell junctions without altering its signaling activities. Our findings provide important insights for understanding the pathogenesis of human palmoplantar keratoderma. PMID- 22315229 TI - HEAT repeat 1 motif is required for B56gamma-containing protein phosphatase 2A (B56gamma-PP2A) holoenzyme assembly and tumor-suppressive function. AB - Protein phosphatase 2A (PP2A) enzyme consists of a heterodimeric core (AC core) comprising a scaffolding subunit (A), a catalytic subunit (C), and a variable regulatory subunit (B). Earlier studies suggest that upon DNA damage, a specific B subunit, B56gamma, bridges the PP2A AC core to p53, leading to dephosphorylation of p53 at Thr-55, induction of the p53 transcriptional target p21, and the inhibition of cell proliferation and transformation. In addition to dephosphorylation of p53, B56gamma-PP2A also inhibits cell proliferation and transformation by an unknown mechanism. B56gamma contains 18 alpha-helices that are organized into eight HEAT (Huntington-elongation-A subunit-TOR) repeat motifs. Although previous crystal structure study has revealed the residues of B56gamma that directly contact the A and C subunits, the contribution of HEAT repeats to holoenzyme assembly and to B56gamma-PP2A tumor-suppressive function remains to be elucidated. Here, we show that HEAT repeat 1 is required for the interaction of B56gamma with the PP2A AC core and, more importantly, for B56gamma PP2A tumor-suppressive function. Within this region, we identified a tumor associated mutation, C39R, which disrupts the interaction of B56gamma with the AC core and thus was unable to mediate dephosphorylation of p53 by PP2A. Furthermore, due to its lack of AC interaction, C39R was also unable to promote the p53-independent tumor-suppressive function of B56gamma-PP2A. This study provides structural insight into the PP2A holoenzyme assembly and emphasizes the importance of HEAT repeat 1 in B56gamma-PP2A tumor-suppressive function. PMID- 22315230 TI - HSP90 and HSP70 proteins are essential for stabilization and activation of WASF3 metastasis-promoting protein. AB - Inactivation of HSP90 and HSP70 leads to loss of invasion in a variety of cancer cell types, presumably as a result of destabilization of, as yet, undefined clients of these molecular chaperones that influence this phenotype. The WASF3 gene has been shown to be up-regulated in high-grade tumors and its down regulation leads to loss of invasion and metastasis. WASF3 phosphorylation by ABL kinase is essential for its ability to regulate invasion. Mass spectroscopy analysis now shows that HSP90 is present in the WASF3 immunocomplex from prostate cancer cells. Inactivation of HSP90 in these and other cell types does not affect WASF3 stability but prevents its phosphoactivation as a result of destabilization of ABL. HSP70 was also found in the WASF3 immunocomplex and inactivation of HSP70 results in destabilization of WASF3 through proteasome degradation. Knockdown of WASF3, HSP90, and HSP70 individually, all lead to loss of invasion but as knockdown of WASF3 in the presence of robust expression of HSP90/70 has the same effect, it seems that the influence these chaperone proteins have on invasion is mediated, at least in part, by their control over the critical invasion promoting capacity of the WASF3 protein. Overexpression of HSP70 in WASF3 null cells does not enhance invasion. These observations suggest that targeting HSP90/70 may have efficacy in reducing cancer cell invasion. PMID- 22315231 TI - Examination of mechanism of N-acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D glucopyranoside deacetylase (MshB) reveals unexpected role for dynamic tyrosine. AB - Actinomycetes are a group of gram-positive bacteria that includes pathogenic mycobacterial species, such as Mycobacterium tuberculosis. These organisms do not have glutathione and instead utilize the small molecule mycothiol (MSH) as their primary reducing agent and for the detoxification of xenobiotics. Due to these important functions, enzymes involved in MSH biosynthesis and MSH-dependent detoxification are targets for drug development. The metal-dependent deacetylase N-acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase (MshB) catalyzes the hydrolysis of N-acetyl-1-D-myo-inosityl-2-amino-2-deoxy alpha-D-glucopyranoside to form 1-D-myo-inosityl-2-amino-2-deoxy-alpha-D glucopyranoside and acetate in MSH biosynthesis. Herein we examine the chemical mechanism of MshB. We demonstrate that the side chains of Asp-15, Tyr-142, His 144, and Asp-146 are important for catalytic activity. We show that NaF is an uncompetitive inhibitor of MshB, consistent with a metal-water/hydroxide functioning as the reactive nucleophile in the catalytic mechanism. We have previously shown that MshB activity has a bell-shaped dependence on pH with pK(a) values of ~7.3 and 10.5 (Huang, X., Kocabas, E. and Hernick, M. (2011) J. Biol. Chem. 286, 20275-20282). Mutagenesis experiments indicate that the observed pK(a) values reflect ionization of Asp-15 and Tyr-142, respectively. Together, findings from our studies suggest that MshB functions through a general acid-base pair mechanism with the side chain of Asp-15 functioning as the general base catalyst and His-144 serving as the general acid catalyst, whereas the side chain of Tyr 142 probably assists in polarizing substrate/stabilizing the oxyanion intermediate. Additionally, our results indicate that Tyr-142 is a dynamic side chain that plays key roles in catalysis, modulating substrate binding, chemistry, and product release. PMID- 22315232 TI - Identification of novel gamma-secretase-associated proteins in detergent resistant membranes from brain. AB - In Alzheimer disease, oligomeric amyloid beta-peptide (Abeta) species lead to synapse loss and neuronal death. gamma-Secretase, the transmembrane protease complex that mediates the final catalytic step that liberates Abeta from its precursor protein (APP), has a multitude of substrates, and therapeutics aimed at reducing Abeta production should ideally be specific for APP cleavage. It has been shown that APP can be processed in lipid rafts, and gamma-secretase associated proteins can affect Abeta production. Here, we use a biotinylated inhibitor for affinity purification of gamma-secretase and associated proteins and mass spectrometry for identification of the purified proteins, and we identify novel gamma-secretase-associated proteins in detergent-resistant membranes from brain. Furthermore, we show by small interfering RNA-mediated knockdown of gene expression that a subset of the gamma-secretase-associated proteins, in particular voltage-dependent anion channel 1 (VDAC1) and contactin associated protein 1 (CNTNAP1), reduced Abeta production (Abeta40 and Abeta42) by around 70%, whereas knockdown of presenilin 1, one of the essential gamma secretase complex components, reduced Abeta production by 50%. Importantly, these proteins had a less pronounced effect on Notch processing. We conclude that VDAC1 and CNTNAP1 associate with gamma-secretase in detergent-resistant membranes and affect APP processing and suggest that molecules that interfere with this interaction could be of therapeutic use for Alzheimer disease. PMID- 22315233 TI - Enantioselective syntheses of rigidiusculamides A and B: revision of the relative stereochemistry of rigidiusculamide A. AB - The first enantioselective synthesis of cytotoxic natural products rigidiusculamides A (ent-21) and B (8) has been achieved by two synthetic routes. The first one is convergent based on the common intermediate 11, obtained through a high yielding SmI(2) -mediated Reformatsky-type reaction. A highly diastereoselective one-pot Dess-Martin periodinane-mediated bis-oxidation allowed the direct conversion of the diastereomeric mixture of 11 into rigidiusculamide B (8). Isolation of minor diastereomer 21, in combination with computational work, allowed us to suggest the structure of the natural rigidiusculamide A to be ent 21, as synthesized by the second route. Four diastereomers (7, ent-7, 22a, and 22b) and an enantiomer (21) of rigidiusculamide A (ent-21) have been synthesized. On the basis of literature precedents and computational work, a biosynthetic pathway for rigidiusculamides A and B was proposed to account for the opposite configuration at C-5 of those two congeners. PMID- 22315234 TI - Hemophagocytic lymphohistiocytosis associated with necrotizing enterocolitis in premature newborns. AB - Hemophagocytic lymphohistiocytosis (HLH) is a systemic disease resulting from the excessive release of inflammatory cytokines by macrophages under prolonged antigenic stimulation. If untreated, it leads to multiorgan failure and death. Necrotizing enterocolitis (NEC) has not previously been associated with HLH. Here we report four preterm infants who were diagnosed with HLH associated with NEC. Two patients received chemotherapy and one survived. The other two infants succumbed to multiorgan failure. These results suggest that NEC may be a common clinical manifestation of HLH in premature neonates. PMID- 22315235 TI - Evaluation of arsenic trioxide by the pediatric preclinical testing program with a focus on Ewing sarcoma. AB - Arsenic trioxide was tested against the PPTP in vitro panel (1.0 nM to 10 uM) and against the PPTP Ewing sarcoma in vivo panel administered intraperitoneally at a dose of 2.5 mg/kg daily * 5 per week for a planned treatment duration of 3 weeks. Arsenic trioxide showed a median relative IC(50) value of 0.9 uM, with Ewing sarcoma cell lines having IC(50) values similar to those of the remaining PPTP cell lines. Arsenic trioxide did not induce significant differences in EFS distribution compared to control in any of the Ewing sarcoma xenografts studied, and no objective responses were observed. PMID- 22315236 TI - Improving the histopathologic diagnosis of pediatric malignancies in a low resource setting by combining focused training and telepathology strategies. AB - BACKGROUND: Accurate diagnosis is critical for optimal management of pediatric cancer. Pathologists with experience in pediatric oncology are in short supply in the developing world. Telepathology is increasingly used for consultations but its overall contribution to diagnostic accuracy is unknown. PROCEDURE: We developed a strategy to provide a focused training in pediatric cancer and telepathology support to pathologists in the developing world. After the training period, we compared trainee's diagnoses with those of an experienced pathologist. We next compared the effectiveness of static versus dynamic telepathology review in 127 cases. Results were compared by Fisher's exact test. RESULTS: The diagnoses of the trainee and the expert pathologist differed in only 6.5% of cases (95% CI, 1.2-20.0%). The overall concordance between the telepathology and original diagnoses was 90.6% (115/127; 95% CI, 84.1-94.6%). CONCLUSIONS: Brief, focused training in pediatric cancer histopathology can improve diagnostic accuracy. Dynamic and static telepathology analyses are equally effective for diagnostic review. PMID- 22315237 TI - New catalytic approaches towards the enantioselective halogenation of alkenes. AB - The addition of electrophilic reagents to the carbon-carbon double bond is one of the most fundamental reactions in organic chemistry. Halogen electrophiles constitute probably the most important class of electrophiles and have been widely used to induce electrophilic addition reactions to alkenes like halolactonizations or dihalogenations. Despite their long history and high importance, catalytic, asymmetric variants of these reactions have been underdeveloped until very recently. During the last two years this has changed and many novel approaches have been reported. This review aims to cover these new developments through discussing the common themes as well as the suggested mechanistic scenarios. PMID- 22315238 TI - School dropout: a major public health challenge: a 10-year prospective study on medical and non-medical social insurance benefits in young adulthood, the Young HUNT 1 Study (Norway). AB - BACKGROUND: School and work participation in adolescence and young adulthood are important for future health and socioeconomic status. The authors studied the association between self-rated health in adolescents, high school dropout and long-term receipt of medical and non-medical social insurance benefits in young adulthood. METHODS: Self-rated health in adolescence was assessed in 8795 adolescents participating in the Norwegian Young-HUNT Study (1995-1997). Linkages to the National Education Database and the National Insurance Administration allowed identification of school dropout and receipt of long-term medical and non medical benefits during a 10-year follow-up (1998-2007). The data were explored by descriptive statistics and by multinomial logistic regression. RESULTS: A total of 17% was registered as being high school dropouts at age 24. The predicted 5-year risk of receiving benefits between ages 24-28 was 21% (95% CI 20% to 23%). High school dropouts had a 5-year risk of receiving benefits of 44% (95% CI 41 to 48) compared with 16% (95% CI 15 to 17) in those who completed high school (adjusted for self-rated health, parental education and sex). There was a 27% school dropout rate in adolescents who reported poor health compared with 16% in those who reported good health. The predicted 5-year risk of receiving any long-term social insurance benefits in adolescents who reported poor health was 33% (95% CI 30 to 37) compared with 20% (95% CI 19 to 21) in those who reported good health. CONCLUSION: The strong association between poor self-rated health in adolescence, high school dropout and reduced work integration needs attention and suggests preventive measures on an individual as well as on a societal level. PMID- 22315239 TI - Childhood residential mobility and health in late adolescence and adulthood: findings from the West of Scotland Twenty-07 Study. AB - BACKGROUND: The relationship between childhood residential mobility and health in the UK is not well established; however, research elsewhere suggests that frequent childhood moves may be associated with poorer health outcomes and behaviours. The aim of this paper was to compare people in the West of Scotland who were residentially stable in childhood with those who had moved in terms of a range of health measures. METHODS: A total of 850 respondents, followed-up for a period of 20 years, were included in this analysis. Childhood residential mobility was derived from the number of addresses lived at between birth and age 18. Multilevel regression was used to investigate the relationship between childhood residential mobility and health in late adolescence (age 18) and adulthood (age 36), accounting for socio-demographic characteristics and frequency of school moves. The authors examined physical health measures, overall health, psychological distress and health behaviours. RESULTS: Twenty per cent of respondents remained stable during childhood, 59% moved one to two times and 21% moved at least three times. For most health measures (except physical health), there was an increased risk of poor health that remained elevated for frequent movers after adjustment for socio-demographic characteristics and school moves (but was only significant for illegal drug use). CONCLUSIONS: Risk of poor health was elevated in adolescence and adulthood with increased residential mobility in childhood, after adjusting for socio-demographic characteristics and school moves. This was true for overall health, psychological distress and health behaviours, but physical health measures were not associated with childhood mobility. PMID- 22315240 TI - Initial testing (stage 1) of the cyclin dependent kinase inhibitor SCH 727965 (dinaciclib) by the pediatric preclinical testing program. AB - BACKGROUND: SCH 727965 is a novel drug in clinical development that potently and selectively inhibits CDK1, CDK2, CDK5, and CDK9. The activity of SCH 727965 was evaluated against the PPTP's in vitro and in vivo panels. PROCEDURES: SCH 727965 was tested against the PPTP in vitro panel using 96 hours exposure at concentrations ranging from 0.1 nM to 1.0 uM. It was tested against the PPTP in vivo panels at a dose of 40 mg/kg administered intraperitoneally twice weekly for 2 weeks and repeated at Day 21 with a total observation period of 6 weeks. RESULTS: The median IC(50) value for the cell lines was 7.5 nM, with less than fourfold range between the minimum (3.4 nM) and maximum (11.2 nM) IC(50) values. SCH 727965 demonstrated an activity pattern consistent with cytotoxicity for most of the cell lines. Forty-three xenograft models were studied and SCH 727965 induced significant delays in event free survival distribution compared to control in 23 of 36 (64%) evaluable solid tumor xenografts and in 3 of 7 ALL xenografts. SCH 727965 did not induce objective responses in the solid tumor panels and the best response observed was stable disease for one osteosarcoma xenograft. In the leukemia panel, there were two objective responses with a complete response observed in a single xenograft. CONCLUSIONS: SCH 727965 shows an interesting pattern of activity suggesting its potential applicability against selected childhood cancers, particularly leukemias. PMID- 22315241 TI - Unravelling molecular responses to moderate dehydration in harvested fruit of sweet orange (Citrus sinensis L. Osbeck) using a fruit-specific ABA-deficient mutant. AB - Water stress affects many agronomic traits that may be regulated by the phytohormone abscisic acid (ABA). Within these traits, loss of fruit quality becomes important in many citrus cultivars that develop peel damage in response to dehydration. To study peel dehydration transcriptional responsiveness in harvested citrus fruit and the putative role of ABA in this process, this study performed a comparative large-scale transcriptional analysis of water-stressed fruits of the wild-type Navelate orange (Citrus sinesis L. Osbeck) and its spontaneous ABA-deficient mutant Pinalate, which is more prone to dehydration and to developing peel damage. Major changes in gene expression occurring in the wild type line were impaired in the mutant fruit. Gene ontology analysis revealed the ability of Navelate fruits to induce the response to water deprivation and di-, tri-valent inorganic cation transport biological processes, as well as repression of the carbohydrate biosynthesis process in the mutant. Exogenous ABA triggered relevant transcriptional changes and repressed the protein ubiquitination process, although it could not fully rescue the physiological behaviour of the mutant. Overall, the results indicated that dehydration responsiveness requires ABA-dependent and -independent signals, and highlight that the ability of citrus fruits to trigger molecular responses against dehydration is an important factor in reducing their susceptibility to developing peel damage. PMID- 22315242 TI - Genome sequence and assembly of Bos indicus. AB - Cattle are divided into 2 groups referred to as taurine and indicine, both of which have been under strong artificial selection due to their importance for human nutrition. A side effect of this domestication includes a loss of genetic diversity within each specialized breed. Recently, the first taurine genome was sequenced and assembled, allowing for a better understanding of this ruminant species. However, genetic information from indicine breeds has been limited. Here, we present the first genome sequence of an indicine breed (Nellore) generated with 52X coverage by SOLiD sequencing platform. As expected, both genomes share high similarity at the nucleotide level for all autosomes and the X chromosome. Regarding the Y chromosome, the homology was considerably lower, most likely due to uncompleted assembly of the taurine Y chromosome. We were also able to cover 97% of the annotated taurine protein-coding genes. PMID- 22315243 TI - Diagnosis and management of Raynaud's phenomenon. PMID- 22315244 TI - A 79 year old man with a lesion on his cheek. PMID- 22315245 TI - Increased HIV testing in men who have sex with men. PMID- 22315246 TI - Pragmatic randomised trials using routine electronic health records: putting them to the test. PMID- 22315247 TI - Responding to domestic violence in primary care. PMID- 22315248 TI - Wendell Potter: pulling the curtains back on spin. PMID- 22315249 TI - Car users in Wales are being urged not to smoke in vehicles carrying children. PMID- 22315250 TI - Europe launches investigation into health risks of faulty breast implants. PMID- 22315251 TI - Imperial Tobacco fails to block ban on cigarette displays in Scotland. PMID- 22315252 TI - Southall plans to sue GMC for delays and an unfair trial. PMID- 22315255 TI - Introduction to the ninth edition: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. AB - The Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines differs substantially from the prior versions both in process and in content. In this introduction, we describe some of the differences and the rationale for the changes. PMID- 22315256 TI - Methodology for the development of antithrombotic therapy and prevention of thrombosis guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. AB - BACKGROUND: To develop the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: ACCP Evidence-Based Clinical Practice Guidelines (AT9), the American College of Chest Physicians (ACCP) assembled a panel of clinical experts, information scientists, decision scientists, and systematic review and guideline methodologists. METHODS: Clinical areas were designated as articles, and a methodologist without important intellectual or financial conflicts of interest led a panel for each article. Only panel members without significant conflicts of interest participated in making recommendations. Panelists specified the population, intervention and alternative, and outcomes for each clinical question and defined criteria for eligible studies. Panelists and an independent evidence based practice center executed systematic searches for relevant studies and evaluated the evidence, and where resources and evidence permitted, they created standardized tables that present the quality of the evidence and key results in a transparent fashion. RESULTS: One or more recommendations relate to each specific clinical question, and each recommendation is clearly linked to the underlying body of evidence. Judgments regarding the quality of evidence and strength of recommendations were based on approaches developed by the Grades of Recommendations, Assessment, Development, and Evaluation Working Group. Panel members constructed scenarios describing relevant health states and rated the disutility associated with these states based on an additional systematic review of evidence regarding patient values and preferences for antithrombotic therapy. These ratings guided value and preference decisions underlying the recommendations. Each topic panel identified questions in which resource allocation issues were particularly important and, for these issues, experts in economic analysis provided additional searches and guidance. CONCLUSIONS: AT9 methodology reflects the current science of evidence-based clinical practice guideline development, with reliance on high-quality systematic reviews, a standardized process for quality assessment of individual studies and the body of evidence, an explicit process for translating the evidence into recommendations, disclosure of financial as well as intellectual conflicts of interest followed by management of disclosed conflicts, and extensive peer review. PMID- 22315257 TI - Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. PMID- 22315258 TI - New antithrombotic drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. AB - This article focuses on new antithrombotic drugs that are in or are entering phase 3 clinical testing. Development of these new agents was prompted by the limitations of existing antiplatelet, anticoagulant, or fibrinolytic drugs. Addressing these unmet needs, this article (1) outlines the rationale for development of new antithrombotic agents; (2) describes the new antiplatelet, anticoagulant, and fibrinolytic drugs; and (3) provides clinical perspectives on the opportunities and challenges faced by these novel agents. PMID- 22315259 TI - Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence Based Clinical Practice Guidelines. AB - BACKGROUND: High-quality anticoagulation management is required to keep these narrow therapeutic index medications as effective and safe as possible. This article focuses on the common important management questions for which, at a minimum, low-quality published evidence is available to guide best practices. METHODS: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS: Most practical clinical questions regarding the management of anticoagulation, both oral and parenteral, have not been adequately addressed by randomized trials. We found sufficient evidence for summaries of recommendations for 23 questions, of which only two are strong rather than weak recommendations. Strong recommendations include targeting an international normalized ratio of 2.0 to 3.0 for patients on vitamin K antagonist therapy (Grade 1B) and not routinely using pharmacogenetic testing for guiding doses of vitamin K antagonist (Grade 1B). Weak recommendations deal with such issues as loading doses, initiation overlap, monitoring frequency, vitamin K supplementation, patient self-management, weight and renal function adjustment of doses, dosing decision support, drug interactions to avoid, and prevention and management of bleeding complications. We also address anticoagulation management services and intensive patient education. CONCLUSIONS: We offer guidance for many common anticoagulation-related management problems. Most anticoagulation management questions have not been adequately studied. PMID- 22315260 TI - Approach to outcome measurement in the prevention of thrombosis in surgical and medical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. AB - This article provides the rationale for the approach to making recommendations primarily used in four articles of the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines: orthopedic surgery, nonorthopedic surgery, nonsurgical patients, and stroke. Some of the early clinical trials of antithrombotic prophylaxis with a placebo or no treatment group used symptomatic VTE and fatal PE to measure efficacy of the treatment. These trials suggest a benefit of thromboprophylaxis in reducing fatal PE. In contrast, most of the recent clinical trials comparing the efficacy of alternative anticoagulants used a surrogate outcome, asymptomatic DVT detected at mandatory venography. This outcome is fundamentally unsatisfactory because it does not allow a trade-off with serious bleeding; that trade-off requires knowledge of the number of symptomatic events that thromboprophylaxis prevents. In this article, we review the merits and limitations of four approaches to estimating reduction in symptomatic thrombosis: (1) direct measurement of symptomatic thrombosis, (2) use of asymptomatic events for relative risks and symptomatic events from randomized controlled trials for baseline risk, (3) use of baseline risk estimates from studies that did not perform surveillance and relative effect from asymptomatic events in randomized controlled trials, and (4) use of available data to estimate the proportion of asymptomatic events that will become symptomatic. All approaches have their limitations. The optimal choice of approach depends on the nature of the evidence available. PMID- 22315261 TI - Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. AB - BACKGROUND: This guideline addressed VTE prevention in hospitalized medical patients, outpatients with cancer, the chronically immobilized, long-distance travelers, and those with asymptomatic thrombophilia. METHODS: This guideline follows methods described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence Based Clinical Practice Guidelines in this supplement. RESULTS: For acutely ill hospitalized medical patients at increased risk of thrombosis, we recommend anticoagulant thromboprophylaxis with low-molecular-weight heparin (LMWH), low dose unfractionated heparin (LDUH) bid, LDUH tid, or fondaparinux (Grade 1B) and suggest against extending the duration of thromboprophylaxis beyond the period of patient immobilization or acute hospital stay (Grade 2B). For acutely ill hospitalized medical patients at low risk of thrombosis, we recommend against the use of pharmacologic prophylaxis or mechanical prophylaxis (Grade 1B). For acutely ill hospitalized medical patients at increased risk of thrombosis who are bleeding or are at high risk for major bleeding, we suggest mechanical thromboprophylaxis with graduated compression stockings (GCS) (Grade 2C) or intermittent pneumatic compression (IPC) (Grade 2C). For critically ill patients, we suggest using LMWH or LDUH thromboprophylaxis (Grade 2C). For critically ill patients who are bleeding or are at high risk for major bleeding, we suggest mechanical thromboprophylaxis with GCS and/or IPC at least until the bleeding risk decreases (Grade 2C). In outpatients with cancer who have no additional risk factors for VTE we suggest against routine prophylaxis with LMWH or LDUH (Grade 2B) and recommend against the prophylactic use of vitamin K antagonists (Grade 1B). CONCLUSIONS: Decisions regarding prophylaxis in nonsurgical patients should be made after consideration of risk factors for both thrombosis and bleeding, clinical context, and patients' values and preferences. PMID- 22315262 TI - Patient values and preferences in decision making for antithrombotic therapy: a systematic review: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. AB - BACKGROUND: Development of clinical practice guidelines involves making trade offs between desirable and undesirable consequences of alternative management strategies. Although the relative value of health states to patients should provide the basis for these trade-offs, few guidelines have systematically summarized the relevant evidence. We conducted a systematic review relating to values and preferences of patients considering antithrombotic therapy. METHODS: We included studies examining patient preferences for alternative approaches to antithrombotic prophylaxis and studies that examined, in the context of antithrombotic prophylaxis or treatment, how patients value alternative health states and experiences with treatment. We conducted a systematic search and compiled structured summaries of the results. Steps in the process that involved judgment were conducted in duplicate. RESULTS: We identified 48 eligible studies. Sixteen dealt with atrial fibrillation, five with VTE, four with stroke or myocardial infarction prophylaxis, six with thrombolysis in acute stroke or myocardial infarction, and 17 with burden of antithrombotic treatment. CONCLUSION: Patient values and preferences regarding thromboprophylaxis treatment appear to be highly variable. Participant responses may depend on their prior experience with the treatments or health outcomes considered as well as on the methods used for preference elicitation. It should be standard for clinical practice guidelines to conduct systematic reviews of patient values and preferences in the specific content area. PMID- 22315263 TI - Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence Based Clinical Practice Guidelines. AB - BACKGROUND: VTE is a common cause of preventable death in surgical patients. METHODS: We developed recommendations for thromboprophylaxis in nonorthopedic surgical patients by using systematic methods as described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS: We describe several alternatives for stratifying the risk of VTE in general and abdominal-pelvic surgical patients. When the risk for VTE is very low (< 0.5%), we recommend that no specific pharmacologic (Grade 1B) or mechanical (Grade 2C) prophylaxis be used other than early ambulation. For patients at low risk for VTE (~1.5%), we suggest mechanical prophylaxis, preferably with intermittent pneumatic compression (IPC), over no prophylaxis (Grade 2C). For patients at moderate risk for VTE (~3%) who are not at high risk for major bleeding complications, we suggest low-molecular-weight heparin (LMWH) (Grade 2B), low-dose unfractionated heparin (Grade 2B), or mechanical prophylaxis with IPC (Grade 2C) over no prophylaxis. For patients at high risk for VTE (~6%) who are not at high risk for major bleeding complications, we recommend pharmacologic prophylaxis with LMWH (Grade 1B) or low-dose unfractionated heparin (Grade 1B) over no prophylaxis. In these patients, we suggest adding mechanical prophylaxis with elastic stockings or IPC to pharmacologic prophylaxis (Grade 2C). For patients at high risk for VTE undergoing abdominal or pelvic surgery for cancer, we recommend extended-duration, postoperative, pharmacologic prophylaxis (4 weeks) with LMWH over limited-duration prophylaxis (Grade 1B). For patients at moderate to high risk for VTE who are at high risk for major bleeding complications or those in whom the consequences of bleeding are believed to be particularly severe, we suggest use of mechanical prophylaxis, preferably with IPC, over no prophylaxis until the risk of bleeding diminishes and pharmacologic prophylaxis may be initiated (Grade 2C). For patients in all risk groups, we suggest that an inferior vena cava filter not be used for primary VTE prevention (Grade 2C) and that surveillance with venous compression ultrasonography should not be performed (Grade 2C). We developed similar recommendations for other nonorthopedic surgical populations. CONCLUSIONS: Optimal thromboprophylaxis in nonorthopedic surgical patients will consider the risks of VTE and bleeding complications as well as the values and preferences of individual patients. PMID- 22315264 TI - Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. AB - This article describes the pharmacology of approved parenteral anticoagulants. These include the indirect anticoagulants, unfractionated heparin (UFH), low molecular-weight heparins (LMWHs), fondaparinux, and danaparoid, as well as the direct thrombin inhibitors hirudin, bivalirudin, and argatroban. UFH is a heterogeneous mixture of glycosaminoglycans that bind to antithrombin via a unique pentasaccharide sequence and catalyze the inactivation of thrombin, factor Xa, and other clotting enzymes. Heparin also binds to cells and plasma proteins other than antithrombin causing unpredictable pharmacokinetic and pharmacodynamic properties and triggering nonhemorrhagic side effects, such as heparin-induced thrombocytopenia (HIT) and osteoporosis. LMWHs have greater inhibitory activity against factor Xa than thrombin and exhibit less binding to cells and plasma proteins than heparin. Consequently, LMWH preparations have more predictable pharmacokinetic and pharmacodynamic properties, have a longer half-life than heparin, and are associated with a lower risk of nonhemorrhagic side effects. LMWHs can be administered once daily or bid by subcutaneous injection, without coagulation monitoring. Based on their greater convenience, LMWHs have replaced UFH for many clinical indications. Fondaparinux, a synthetic pentasaccharide, catalyzes the inhibition of factor Xa, but not thrombin, in an antithrombin dependent fashion. Fondaparinux binds only to antithrombin. Therefore, fondaparinux-associated HIT or osteoporosis is unlikely to occur. Fondaparinux exhibits complete bioavailability when administered subcutaneously, has a longer half-life than LMWHs, and is given once daily by subcutaneous injection in fixed doses, without coagulation monitoring. Three additional parenteral direct thrombin inhibitors and danaparoid are approved as alternatives to heparin in patients with HIT. PMID- 22315265 TI - Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence Based Clinical Practice Guidelines. AB - BACKGROUND: VTE is a serious, but decreasing complication following major orthopedic surgery. This guideline focuses on optimal prophylaxis to reduce postoperative pulmonary embolism and DVT. METHODS: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence Based Clinical Practice Guidelines in this supplement. RESULTS: In patients undergoing major orthopedic surgery, we recommend the use of one of the following rather than no antithrombotic prophylaxis: low-molecular-weight heparin; fondaparinux; dabigatran, apixaban, rivaroxaban (total hip arthroplasty or total knee arthroplasty but not hip fracture surgery); low-dose unfractionated heparin; adjusted-dose vitamin K antagonist; aspirin (all Grade 1B); or an intermittent pneumatic compression device (IPCD) (Grade 1C) for a minimum of 10 to 14 days. We suggest the use of low-molecular-weight heparin in preference to the other agents we have recommended as alternatives (Grade 2C/2B), and in patients receiving pharmacologic prophylaxis, we suggest adding an IPCD during the hospital stay (Grade 2C). We suggest extending thromboprophylaxis for up to 35 days (Grade 2B). In patients at increased bleeding risk, we suggest an IPCD or no prophylaxis (Grade 2C). In patients who decline injections, we recommend using apixaban or dabigatran (all Grade 1B). We suggest against using inferior vena cava filter placement for primary prevention in patients with contraindications to both pharmacologic and mechanical thromboprophylaxis (Grade 2C). We recommend against Doppler (or duplex) ultrasonography screening before hospital discharge (Grade 1B). For patients with isolated lower-extremity injuries requiring leg immobilization, we suggest no thromboprophylaxis (Grade 2B). For patients undergoing knee arthroscopy without a history of VTE, we suggest no thromboprophylaxis (Grade 2B). CONCLUSIONS: Optimal strategies for thromboprophylaxis after major orthopedic surgery include pharmacologic and mechanical approaches. PMID- 22315266 TI - Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence Based Clinical Practice Guidelines. AB - BACKGROUND: This guideline addresses the management of patients who are receiving anticoagulant or antiplatelet therapy and require an elective surgery or procedure. METHODS: The methods herein follow those discussed in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. RESULTS: In patients requiring vitamin K antagonist (VKA) interruption before surgery, we recommend stopping VKAs 5 days before surgery instead of a shorter time before surgery (Grade 1B). In patients with a mechanical heart valve, atrial fibrillation, or VTE at high risk for thromboembolism, we suggest bridging anticoagulation instead of no bridging during VKA interruption (Grade 2C); in patients at low risk, we suggest no bridging instead of bridging (Grade 2C). In patients who require a dental procedure, we suggest continuing VKAs with an oral prohemostatic agent or stopping VKAs 2 to 3 days before the procedure instead of alternative strategies (Grade 2C). In moderate- to high-risk patients who are receiving acetylsalicylic acid (ASA) and require noncardiac surgery, we suggest continuing ASA around the time of surgery instead of stopping ASA 7 to 10 days before surgery (Grade 2C). In patients with a coronary stent who require surgery, we recommend deferring surgery > 6 weeks after bare-metal stent placement and > 6 months after drug eluting stent placement instead of undertaking surgery within these time periods (Grade 1C); in patients requiring surgery within 6 weeks of bare-metal stent placement or within 6 months of drug-eluting stent placement, we suggest continuing antiplatelet therapy perioperatively instead of stopping therapy 7 to 10 days before surgery (Grade 2C). CONCLUSIONS: Perioperative antithrombotic management is based on risk assessment for thromboembolism and bleeding, and recommended approaches aim to simplify patient management and minimize adverse clinical outcomes. PMID- 22315267 TI - Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. AB - BACKGROUND: Objective testing for DVT is crucial because clinical assessment alone is unreliable and the consequences of misdiagnosis are serious. This guideline focuses on the identification of optimal strategies for the diagnosis of DVT in ambulatory adults. METHODS: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. RESULTS: We suggest that clinical assessment of pretest probability of DVT, rather than performing the same tests in all patients, should guide the diagnostic process for a first lower extremity DVT (Grade 2B). In patients with a low pretest probability of first lower extremity DVT, we recommend initial testing with D-dimer or ultrasound (US) of the proximal veins over no diagnostic testing (Grade 1B), venography (Grade 1B), or whole-leg US (Grade 2B). In patients with moderate pretest probability, we recommend initial testing with a highly sensitive D-dimer, proximal compression US, or whole-leg US rather than no testing (Grade 1B) or venography (Grade 1B). In patients with a high pretest probability, we recommend proximal compression or whole-leg US over no testing (Grade 1B) or venography (Grade 1B). CONCLUSIONS: Favored strategies for diagnosis of first DVT combine use of pretest probability assessment, D dimer, and US. There is lower-quality evidence available to guide diagnosis of recurrent DVT, upper extremity DVT, and DVT during pregnancy. PMID- 22315268 TI - Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. AB - BACKGROUND: This article addresses the treatment of VTE disease. METHODS: We generated strong (Grade 1) and weak (Grade 2) recommendations based on high quality (Grade A), moderate-quality (Grade B), and low-quality (Grade C) evidence. RESULTS: For acute DVT or pulmonary embolism (PE), we recommend initial parenteral anticoagulant therapy (Grade 1B) or anticoagulation with rivaroxaban. We suggest low-molecular-weight heparin (LMWH) or fondaparinux over IV unfractionated heparin (Grade 2C) or subcutaneous unfractionated heparin (Grade 2B). We suggest thrombolytic therapy for PE with hypotension (Grade 2C). For proximal DVT or PE, we recommend treatment of 3 months over shorter periods (Grade 1B). For a first proximal DVT or PE that is provoked by surgery or by a nonsurgical transient risk factor, we recommend 3 months of therapy (Grade 1B; Grade 2B if provoked by a nonsurgical risk factor and low or moderate bleeding risk); that is unprovoked, we suggest extended therapy if bleeding risk is low or moderate (Grade 2B) and recommend 3 months of therapy if bleeding risk is high (Grade 1B); and that is associated with active cancer, we recommend extended therapy (Grade 1B; Grade 2B if high bleeding risk) and suggest LMWH over vitamin K antagonists (Grade 2B). We suggest vitamin K antagonists or LMWH over dabigatran or rivaroxaban (Grade 2B). We suggest compression stockings to prevent the postthrombotic syndrome (Grade 2B). For extensive superficial vein thrombosis, we suggest prophylactic-dose fondaparinux or LMWH over no anticoagulation (Grade 2B), and suggest fondaparinux over LMWH (Grade 2C). CONCLUSION: Strong recommendations apply to most patients, whereas weak recommendations are sensitive to differences among patients, including their preferences. PMID- 22315269 TI - Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. AB - BACKGROUND: The objective of this article is to summarize the published literature concerning the pharmacokinetics and pharmacodynamics of oral anticoagulant drugs that are currently available for clinical use and other aspects related to their management. METHODS: We carried out a standard review of published articles focusing on the laboratory and clinical characteristics of the vitamin K antagonists; the direct thrombin inhibitor, dabigatran etexilate; and the direct factor Xa inhibitor, rivaroxaban RESULTS: The antithrombotic effect of each oral anticoagulant drug, the interactions, and the monitoring of anticoagulation intensity are described in detail and discussed without providing specific recommendations. Moreover, we describe and discuss the clinical applications and optimal dosages of oral anticoagulant therapies, practical issues related to their initiation and monitoring, adverse events such as bleeding and other potential side effects, and available strategies for reversal. CONCLUSIONS: There is a large amount of evidence on laboratory and clinical characteristics of vitamin K antagonists. A growing body of evidence is becoming available on the first new oral anticoagulant drugs available for clinical use, dabigatran and rivaroxaban. PMID- 22315270 TI - Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. AB - BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an antibody-mediated adverse drug reaction that can lead to devastating thromboembolic complications, including pulmonary embolism, ischemic limb necrosis necessitating limb amputation, acute myocardial infarction, and stroke. METHODS: The methods of this guideline follow the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS: Among the key recommendations for this article are the following: For patients receiving heparin in whom clinicians consider the risk of HIT to be > 1%, we suggest that platelet count monitoring be performed every 2 or 3 days from day 4 to day 14 (or until heparin is stopped, whichever occurs first) (Grade 2C). For patients receiving heparin in whom clinicians consider the risk of HIT to be < 1%, we suggest that platelet counts not be monitored (Grade 2C). In patients with HIT with thrombosis (HITT) or isolated HIT who have normal renal function, we suggest the use of argatroban or lepirudin or danaparoid over other nonheparin anticoagulants (Grade 2C). In patients with HITT and renal insufficiency, we suggest the use of argatroban over other nonheparin anticoagulants (Grade 2C). In patients with acute HIT or subacute HIT who require urgent cardiac surgery, we suggest the use of bivalirudin over other nonheparin anticoagulants or heparin plus antiplatelet agents (Grade 2C). CONCLUSIONS: Further studies evaluating the role of fondaparinux and the new oral anticoagulants in the treatment of HIT are needed. PMID- 22315271 TI - Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence Based Clinical Practice Guidelines. AB - BACKGROUND: The risk of stroke varies considerably across different groups of patients with atrial fibrillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. METHODS: We used the methods described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. RESULTS: For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS(2) [congestive heart failure, hypertension, age >= 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at intermediate risk of stroke (eg, CHADS(2) score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS(2) score of >= 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabigatran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy. CONCLUSIONS: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS(2) score of >= 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized approach. PMID- 22315272 TI - Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. AB - BACKGROUND: Antithrombotic therapy in valvular disease is important to mitigate thromboembolism, but the hemorrhagic risk imposed must be considered. METHODS: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS: In rheumatic mitral disease, we recommend vitamin K antagonist (VKA) therapy when the left atrial diameter is > 55 mm (Grade 2C) or when complicated by left atrial thrombus (Grade 1A). In candidates for percutaneous mitral valvotomy with left atrial thrombus, we recommend VKA therapy until thrombus resolution, and we recommend abandoning valvotomy if the thrombus fails to resolve (Grade 1A). In patients with patent foramen ovale (PFO) and stroke or transient ischemic attack, we recommend initial aspirin therapy (Grade 1B) and suggest substitution of VKA if recurrence (Grade 2C). In patients with cryptogenic stroke and DVT and a PFO, we recommend VKA therapy for 3 months (Grade 1B) and consideration of PFO closure (Grade 2C). We recommend against the use of anticoagulant (Grade 1C) and antiplatelet therapy (Grade 1B) for native valve endocarditis. We suggest holding VKA therapy until the patient is stabilized without neurologic complications for infective endocarditis of a prosthetic valve (Grade 2C). In the first 3 months after bioprosthetic valve implantation, we recommend aspirin for aortic valves (Grade 2C), the addition of clopidogrel to aspirin if the aortic valve is transcatheter (Grade 2C), and VKA therapy with a target international normalized ratio (INR) of 2.5 for mitral valves (Grade 2C). After 3 months, we suggest aspirin therapy (Grade 2C). We recommend early bridging of mechanical valve patients to VKA therapy with unfractionated heparin (DVT dosing) or low-molecular-weight heparin (Grade 2C). We recommend long-term VKA therapy for all mechanical valves (Grade 1B): target INR 2.5 for aortic (Grade 1B) and 3.0 for mitral or double valve (Grade 2C). In patients with mechanical valves at low bleeding risk, we suggest the addition of low-dose aspirin (50-100 mg/d) (Grade 1B). In valve repair patients, we suggest aspirin therapy (Grade 2C). In patients with thrombosed prosthetic valve, we recommend fibrinolysis for right-sided valves and left-sided valves with thrombus area < 0.8 cm(2) (Grade 2C). For patients with left-sided prosthetic valve thrombosis and thrombus area >= 0.8 cm(2), we recommend early surgery (Grade 2C). CONCLUSIONS: These antithrombotic guidelines provide recommendations based on the optimal balance of thrombotic and hemorrhagic risk. PMID- 22315273 TI - Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. AB - OBJECTIVES: This article provides recommendations on the use of antithrombotic therapy in patients with stroke or transient ischemic attack (TIA). METHODS: We generated treatment recommendations (Grade 1) and suggestions (Grade 2) based on high (A), moderate (B), and low (C) quality evidence. RESULTS: In patients with acute ischemic stroke, we recommend IV recombinant tissue plasminogen activator (r-tPA) if treatment can be initiated within 3 h (Grade 1A) or 4.5 h (Grade 2C) of symptom onset; we suggest intraarterial r-tPA in patients ineligible for IV tPA if treatment can be initiated within 6 h (Grade 2C); we suggest against the use of mechanical thrombectomy (Grade 2C) although carefully selected patients may choose this intervention; and we recommend early aspirin therapy at a dose of 160 to 325 mg (Grade 1A). In patients with acute stroke and restricted mobility, we suggest the use of prophylactic-dose heparin or intermittent pneumatic compression devices (Grade 2B) and suggest against the use of elastic compression stockings (Grade 2B). In patients with a history of noncardioembolic ischemic stroke or TIA, we recommend long-term treatment with aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) over no antiplatelet therapy (Grade 1A), oral anticoagulants (Grade 1B), the combination of clopidogrel plus aspirin (Grade 1B), or triflusal (Grade 2B). Of the recommended antiplatelet regimens, we suggest clopidogrel or aspirin/extended-release dipyridamole over aspirin (Grade 2B) or cilostazol (Grade 2C). In patients with a history of stroke or TIA and atrial fibrillation we recommend oral anticoagulation over no antithrombotic therapy, aspirin, and combination therapy with aspirin and clopidogrel (Grade 1B). CONCLUSIONS: These recommendations can help clinicians make evidence-based treatment decisions with their patients who have had strokes. PMID- 22315274 TI - Primary and secondary prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. AB - BACKGROUND: This guideline focuses on long-term administration of antithrombotic drugs designed for primary and secondary prevention of cardiovascular disease, including two new antiplatelet therapies. METHODS: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence Based Clinical Practice Guidelines in this supplement. RESULTS: We present 23 recommendations for pertinent clinical questions. For primary prevention of cardiovascular disease, we suggest low-dose aspirin (75-100 mg/d) in patients aged > 50 years over no aspirin therapy (Grade 2B). For patients with established coronary artery disease, defined as patients 1-year post-acute coronary syndrome, with prior revascularization, coronary stenoses > 50% by coronary angiogram, and/or evidence for cardiac ischemia on diagnostic testing, we recommend long term low-dose aspirin or clopidogrel (75 mg/d) (Grade 1A). For patients with acute coronary syndromes who undergo percutaneous coronary intervention (PCI) with stent placement, we recommend for the first year dual antiplatelet therapy with low-dose aspirin in combination with ticagrelor 90 mg bid, clopidogrel 75 mg/d, or prasugrel 10 mg/d over single antiplatelet therapy (Grade 1B). For patients undergoing elective PCI with stent placement, we recommend aspirin (75 325 mg/d) and clopidogrel for a minimum duration of 1 month (bare-metal stents) or 3 to 6 months (drug-eluting stents) (Grade 1A). We suggest continuing low-dose aspirin plus clopidogrel for 12 months for all stents (Grade 2C). Thereafter, we recommend single antiplatelet therapy over continuation of dual antiplatelet therapy (Grade 1B). CONCLUSIONS: Recommendations continue to favor single antiplatelet therapy for patients with established coronary artery disease. For patients with acute coronary syndromes or undergoing elective PCI with stent placement, dual antiplatelet therapy for up to 1 year is warranted. PMID- 22315275 TI - Antithrombotic therapy in peripheral artery disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence Based Clinical Practice Guidelines. AB - BACKGROUND: This guideline focuses on antithrombotic drug therapies for primary and secondary prevention of cardiovascular disease as well as for the relief of lower-extremity symptoms and critical ischemia in persons with peripheral arterial disease (PAD). METHODS: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS: The most important of our 20 recommendations are as follows. In patients aged >= 50 years with asymptomatic PAD or asymptomatic carotid stenosis, we suggest aspirin (75-100 mg/d) over no therapy (Grade 2B) for the primary prevention of cardiovascular events. For secondary prevention of cardiovascular disease in patients with symptomatic PAD (including patients before and after peripheral arterial bypass surgery or percutaneous transluminal angioplasty), we recommend long-term aspirin (75-100 mg/d) or clopidogrel (75 mg/d) (Grade 1A). We recommend against the use of warfarin plus aspirin in patients with symptomatic PAD (Grade 1B). For patients undergoing peripheral artery percutaneous transluminal angioplasty with stenting, we suggest single rather than dual antiplatelet therapy (Grade 2C). For patients with refractory claudication despite exercise therapy and smoking cessation, we suggest addition of cilostazol (100 mg bid) to aspirin (75-100 mg/d) or clopidogrel (75 mg/d) (Grade 2C). In patients with critical limb ischemia and rest pain unable to undergo revascularization, we suggest the use of prostanoids (Grade 2C). In patients with acute limb ischemia due to acute thrombosis or embolism, we recommend surgery over peripheral arterial thrombolysis (Grade 1B). CONCLUSIONS: Recommendations continue to favor single antiplatelet therapy for primary and secondary prevention of cardiovascular events in most patients with asymptomatic PAD, symptomatic PAD, and asymptomatic carotid stenosis. Additional therapies for relief of limb symptoms should be considered only after exercise therapy, smoking cessation, and evaluation for peripheral artery revascularization. PMID- 22315276 TI - VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. AB - BACKGROUND: The use of anticoagulant therapy during pregnancy is challenging because of the potential for both fetal and maternal complications. This guideline focuses on the management of VTE and thrombophilia as well as the use of antithrombotic agents during pregnancy. METHODS: The methods of this guideline follow the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS: We recommend low-molecular weight heparin for the prevention and treatment of VTE in pregnant women instead of unfractionated heparin (Grade 1B). For pregnant women with acute VTE, we suggest that anticoagulants be continued for at least 6 weeks postpartum (for a minimum duration of therapy of 3 months) compared with shorter durations of treatment (Grade 2C). For women who fulfill the laboratory criteria for antiphospholipid antibody (APLA) syndrome and meet the clinical APLA criteria based on a history of three or more pregnancy losses, we recommend antepartum administration of prophylactic or intermediate-dose unfractionated heparin or prophylactic low-molecular-weight heparin combined with low-dose aspirin (75-100 mg/d) over no treatment (Grade 1B). For women with inherited thrombophilia and a history of pregnancy complications, we suggest not to use antithrombotic prophylaxis (Grade 2C). For women with two or more miscarriages but without APLA or thrombophilia, we recommend against antithrombotic prophylaxis (Grade 1B). CONCLUSIONS: Most recommendations in this guideline are based on observational studies and extrapolation from other populations. There is an urgent need for appropriately designed studies in this population. PMID- 22315279 TI - Epidemiologic consequences of microvariation in Mycobacterium tuberculosis. AB - BACKGROUND: Evidence from genotype-phenotype studies suggests that genetic diversity in pathogens have clinically relevant manifestations that can impact outcome of infection and epidemiologic success. We studied 5 closely related Mycobacterium tuberculosis strains that collectively caused extensive disease (n = 862), particularly among US-born tuberculosis patients. METHODS: Representative isolates were selected using population-based genotyping data from New York City and New Jersey. Growth and cytokine/chemokine response were measured in infected human monocytes. Survival was determined in aerosol-infected guinea pigs. RESULTS: Multiple genotyping methods and phylogenetically informative synonymous single nucleotide polymorphisms showed that all strains were related by descent. In axenic culture, all strains grew similarly. However, infection of monocytes revealed 2 growth phenotypes, slower (doubling ~55 hours) and faster (~25 hours). The faster growing strains elicited more tumor necrosis factor alpha and interleukin 1beta than the slower growing strains, even after heat killing, and caused accelerated death of infected guinea pigs (~9 weeks vs 24 weeks) associated with increased lung inflammation/pathology. Epidemiologically, the faster growing strains were associated with human immunodeficiency virus and more limited in spread, possibly related to their inherent ability to induce a strong protective innate immune response in immune competent hosts. CONCLUSIONS: Natural variation, with detectable phenotypic changes, among closely related clinical isolates of M. tuberculosis may alter epidemiologic patterns in human populations. PMID- 22315278 TI - Antiplatelet drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. AB - The article describes the mechanisms of action, pharmacokinetics, and pharmacodynamics of aspirin, dipyridamole, cilostazol, the thienopyridines, and the glycoprotein IIb/IIIa antagonists. The relationships among dose, efficacy, and safety are discussed along with a mechanistic overview of results of randomized clinical trials. The article does not provide specific management recommendations but highlights important practical aspects of antiplatelet therapy, including optimal dosing, the variable balance between benefits and risks when antiplatelet therapies are used alone or in combination with other antiplatelet drugs in different clinical settings, and the implications of persistently high platelet reactivity despite such treatment. PMID- 22315280 TI - OX40 ligand fusion protein delivered simultaneously with the BCG vaccine provides superior protection against murine Mycobacterium tuberculosis infection. AB - Mycobacterium tuberculosis infection claims approximately 2 million lives per year, and improved efficacy of the BCG vaccine remains a World Health Organization priority. Successful vaccination against M. tuberculosis requires the induction and maintenance of T cells. Targeting molecules that promote T-cell survival may therefore provide an alternative strategy to classic adjuvants. We show that the interaction between T-cell-expressed OX40 and OX40L on antigen presenting cells is critical for effective immunity to BCG. However, because OX40L is lost rapidly from antigen-presenting cells following BCG vaccination, maintenance of OX40-expressing vaccine-activated T cells may not be optimal. Delivering an OX40L:Ig fusion protein simultaneously with BCG provided superior immunity to intravenous and aerosol M. tuberculosis challenge even 6 months after vaccination, an effect that depends on natural killer 1.1(+) cells. Attenuated vaccines may therefore lack sufficient innate stimulation to maintain vaccine specific T cells, which can be replaced by reagents binding inducible T-cell costimulators. PMID- 22315281 TI - Species-specific recognition of Aspergillus fumigatus by Toll-like receptor 1 and Toll-like receptor 6. AB - BACKGROUND: Aspergillus fumigatus causes invasive aspergillosis, a potentially fatal infection in oncohematological patients. Innate immune detection of A. fumigatus involves Toll-like receptor (TLR) 4 and TLR2, which forms a heterodimer with either TLR1 or TLR6. The role of those coreceptors in Aspergillus sensing is unknown. METHODS: Cytokine production was measured in bone marrow-derived macrophages (BMDMs) from wild-type (WT) and TLR-deficient mice after incubation with a WT and an immunogenic RodA-deficient (DeltarodA-47) strain of A. fumigatus and in lungs from these mice after intranasal mold inoculation. Aspergillus fumigatus-mediated NF-kappaB activation was measured in HEK293T cells transfected with plasmids expressing mouse or human TLRs. RESULTS: Bone marrow-derived macrophages from TLR1- and TLR6-deficient mice produced lower amounts of interleukin 12p40, CXCL2, interleukin 6, and tumor necrosis factor alpha than BMDMs from WT mice after stimulation with A. fumigatus. Lungs from TLR1- and TLR6 deficient mice had diminished CXCL1 and CXCL2 production and increased fungal burden after intranasal inoculation of DeltarodA A. fumigatus compared with lungs from WT mice. DeltarodA strain-mediated NF-kappaB activation was observed in HEK293T cells expressing mouse TLR2/1, mouse TLR2/6, and human TLR2/1 but not human TLR2/6. CONCLUSIONS: Innate immune detection of A. fumigatus is mediated by TLR4 and TLR2 together with TLR1 or TLR6 in mice and TLR1 but not TLR6 in humans. PMID- 22315283 TI - Martin McKee replies to Andrew Lansley. PMID- 22315282 TI - Systemic and vascular oxidation limits the efficacy of oral tetrahydrobiopterin treatment in patients with coronary artery disease. AB - BACKGROUND: The endothelial nitric oxide synthase cofactor tetrahydrobiopterin (BH4) plays a pivotal role in maintaining endothelial function in experimental vascular disease models and in humans. Augmentation of endogenous BH4 levels by oral BH4 treatment has been proposed as a potential therapeutic strategy in vascular disease states. We sought to determine the mechanisms relating exogenous BH4 to human vascular function and to determine oral BH4 pharmacokinetics in both plasma and vascular tissue in patients with coronary artery disease. METHODS AND RESULTS: Forty-nine patients with coronary artery disease were randomized to receive low-dose (400 mg/d) or high-dose (700 mg/d) BH4 or placebo for 2 to 6 weeks before coronary artery bypass surgery. Vascular function was quantified by magnetic resonance imaging before and after treatment, along with plasma BH4 levels. Vascular superoxide, endothelial function, and BH4 levels were determined in segments of saphenous vein and internal mammary artery. Oral BH4 treatment significantly augmented BH4 levels in plasma and in saphenous vein (but not internal mammary artery) but also increased levels of the oxidation product dihydrobiopterin (BH2), which lacks endothelial nitric oxide synthase cofactor activity. There was no effect of BH4 treatment on vascular function or superoxide production. Supplementation of human vessels and blood with BH4 ex vivo revealed rapid oxidation of BH4 to BH2 with predominant BH2 uptake by vascular tissue. CONCLUSIONS: Oral BH4 treatment augments total biopterin levels in patients with established coronary artery disease but has no net effect on vascular redox state or endothelial function owing to systemic and vascular oxidation of BH4. Alternative strategies are required to target BH4-dependent endothelial function in established vascular disease states. PMID- 22315284 TI - The management of the NHS in England. PMID- 22315285 TI - Endovascular treatment with 'kissing' flow diverter stents of two unruptured aneurysms at a fenestrated vertebrobasilar junction. AB - BACKGROUND AND PURPOSE: Fenestration of the vertebrobasilar junction (VBJ) is a rare condition which may be associated with the presence of aneurysms. The endovascular approach is usually the first-line treatment in these cases since the location of the aneurysm may be unsuitable for a surgical approach. This anatomical variation may even influence the endovascular strategy, particularly in those cases in which the sacrifice of a vessel could be avoided. This paper describes an innovative approach of flow diversion in such challenging situations. METHODS: Two women were admitted after an occasional diagnosis of an aneurysm arising from a fenestrated VBJ. In both cases the endovascular approach was performed with two flow diverter stents and dual antiplatelet therapy was administered for 6 months. RESULTS: Complete exclusion of the two aneurysms was obtained after 6 and 7 months, respectively, and the clinical outcome was excellent. CONCLUSIONS: Endovascular treatment of unruptured aneurysms located on a fenestrated VBJ with flow diverter stents represents a valid therapeutic approach with excellent clinical and radiological outcomes. PMID- 22315286 TI - Incomplete mechanical recanalization of middle cerebral artery occlusions facilitates endogenous recanalization within 5 h. AB - BACKGROUND AND PURPOSE: Successful revascularization can often improve functional outcome after large intracranial arterial occlusions. However, incomplete or unsuccessful recanalization is often the end result after attempted mechanical thrombectomy. A study was undertaken to determine whether partial recanalization of proximal isolated middle cerebral artery (MCA) occlusions facilitates endogenous thrombolysis and spontaneous recanalization. METHODS: We retrospectively analyzed consecutive patients with acute ischemic stroke undergoing mechanical thrombectomy using the Merci Retriever System for occlusions involving any portion of the M1 segment of the MCA. Only those patients with a residual obstruction of the proximal MCA segments were included. The rates of facilitated endogenous recanalization (FER5) by imaging within the 5 h following intervention were compared in patients with partial proximal recanalization and those in whom recanalization was unsuccessful. RESULTS: Forty two patients were included in the analysis. Twenty-six patients had good recanalization of the proximal aspect of the target lesion with an arterial occlusive lesion score of 2 or 3 but a residual partial or total occlusion of the MCA, while 16 patients failed to recanalize any portion of the target occlusion. Twelve patients (46%) in the first group and only one (5.9%) in the second group had facilitated endogenous recanalization on interval imaging 5 h after intervention (OR 12.9, 95% CI 1.5 to 112.2). Nine patients with proximal recanalization had good clinical outcomes at discharge (mRS <=2) compared with none without recanalization (p=0.01), but FER did not have a relationship with clinical outcome. CONCLUSIONS: Despite initially incomplete proximal mechanical thrombectomy, nearly half of all patients with residual M1 occlusions will undergo further endogenous recanalization within the subsequent 5 h. PMID- 22315287 TI - Might wipe clean covers for mobile phones reduce risk of spread of pathogens? PMID- 22315277 TI - Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence Based Clinical Practice Guidelines. AB - BACKGROUND: Neonates and children differ from adults in physiology, pharmacologic responses to drugs, epidemiology, and long-term consequences of thrombosis. This guideline addresses optimal strategies for the management of thrombosis in neonates and children. METHODS: The methods of this guideline follow those described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. RESULTS: We suggest that where possible, pediatric hematologists with experience in thromboembolism manage pediatric patients with thromboembolism (Grade 2C). When this is not possible, we suggest a combination of a neonatologist/pediatrician and adult hematologist supported by consultation with an experienced pediatric hematologist (Grade 2C). We suggest that therapeutic unfractionated heparin in children is titrated to achieve a target anti-Xa range of 0.35 to 0.7 units/mL or an activated partial thromboplastin time range that correlates to this anti-Xa range or to a protamine titration range of 0.2 to 0.4 units/mL (Grade 2C). For neonates and children receiving either daily or bid therapeutic low-molecular-weight heparin, we suggest that the drug be monitored to a target range of 0.5 to 1.0 units/mL in a sample taken 4 to 6 h after subcutaneous injection or, alternatively, 0.5 to 0.8 units/mL in a sample taken 2 to 6 h after subcutaneous injection (Grade 2C). CONCLUSIONS: The evidence supporting most recommendations for antithrombotic therapy in neonates and children remains weak. Studies addressing appropriate drug target ranges and monitoring requirements are urgently required in addition to site- and clinical situation-specific thrombosis management strategies. PMID- 22315288 TI - Telemedicine doctors abroad don't have to register with the GMC. PMID- 22315289 TI - Daily contact with a nurse may be more important than high tech telecare. PMID- 22315290 TI - Health and wellbeing boards are at risk in fury over NHS reforms. PMID- 22315291 TI - Full steam ahead on to the rocks. PMID- 22315292 TI - Are those who quit smoking paying with their lives because of NRT's failure? PMID- 22315293 TI - Midwifery ratios might explain some differences in perinatal and maternal outcomes. PMID- 22315294 TI - We need more data before reconfiguring maternity services. PMID- 22315295 TI - Should healthcare purchasers be funding home birth for nulliparous women? PMID- 22315296 TI - Lansley fails to see impact and damage of his reforms. PMID- 22315297 TI - Dynamic interaction between slightly right wing minister and slightly left wing Mandarins. PMID- 22315298 TI - Contaminated drugs are held responsible for 120 deaths in Pakistan. PMID- 22315299 TI - European agency prepares for new rules to improve drug safety. PMID- 22315300 TI - GMC says doctors can give medical notes to patients who want to end their lives. PMID- 22315301 TI - Around 1000 women with private sector PIP implants seek NHS help. PMID- 22315302 TI - Baby knows best? The impact of weaning style on food preferences and body mass index in early childhood in a case-controlled sample. AB - OBJECTIVE: The impact of different weaning methods on food preferences and body mass index (BMI) in early childhood is not known. Here, we examine if weaning method-baby-led weaning versus traditional spoon feeding-influences food preferences and health-related outcomes. DESIGN, SETTING AND PARTICIPANTS: Parents (n=155) recruited through the Nottingham Toddler laboratory and relevant internet sites completed a questionnaire concerning (1) infant feeding and weaning style (baby-led=92, spoon-fed=63, age range 20-78 months), (2) their child's preference for 151 foods (analysed by common food categories, eg, carbohydrates, proteins, dairy) and (3) exposure (frequency of consumption). Food preference and exposure data were analysed using a case-controlled matched sample to account for the effect of age on food preference. All other analyses were conducted with the whole sample. MAIN OUTCOME MEASURES: The primary outcome measures were food preferences, exposure and weaning style. The secondary outcome measures were BMI and picky eating. RESULTS: Compared to the spoon-fed group, the baby-led group demonstrated (1) significantly increased liking for carbohydrates (no other differences in preference were found) and (2) carbohydrates to be their most preferred foods (compared to sweet foods for the spoon-fed group). Preference and exposure ratings were not influenced by socially desirable responding or socioeconomic status, although an increased liking for vegetables was associated with higher social class. There was an increased incidence of (1) underweight in the baby-led group and (2) obesity in the spoon-fed group. No difference in picky eating was found between the two weaning groups. CONCLUSIONS: Weaning style impacts on food preferences and health in early childhood. Our results suggest that infants weaned through the baby-led approach learn to regulate their food intake in a manner, which leads to a lower BMI and a preference for healthy foods like carbohydrates. This has implications for combating the well-documented rise of obesity in contemporary societies. PMID- 22315303 TI - Interbirth interval is associated with childhood type 1 diabetes risk. AB - Short interbirth interval has been associated with maternal complications and childhood autism and leukemia, possibly due to deficiencies in maternal micronutrients at conception or increased exposure to sibling infections. A possible association between interbirth interval and subsequent risk of childhood type 1 diabetes has not been investigated. A secondary analysis of 14 published observational studies of perinatal risk factors for type 1 diabetes was conducted. Risk estimates of diabetes by category of interbirth interval were calculated for each study. Random effects models were used to calculate pooled odds ratios (ORs) and investigate heterogeneity between studies. Overall, 2,787 children with type 1 diabetes were included. There was a reduction in the risk of childhood type 1 diabetes in children born to mothers after interbirth intervals <3 years compared with longer interbirth intervals (OR 0.82 [95% CI 0.72-0.93]). Adjustments for various potential confounders little altered this estimate. In conclusion, there was evidence of a 20% reduction in the risk of childhood diabetes in children born to mothers after interbirth intervals <3 years. PMID- 22315304 TI - Type 1 diabetes is associated with enterovirus infection in gut mucosa. AB - Enterovirus infections have been linked to type 1 diabetes in several studies. Enteroviruses also have tropism to pancreatic islets and can cause beta-cell damage in experimental models. Viral persistence has been suspected to be an important pathogenetic factor. This study evaluates whether gut mucosa is a reservoir for enterovirus persistence in type 1 diabetic patients. Small-bowel mucosal biopsy samples from 39 type 1 diabetic patients, 41 control subjects, and 40 celiac disease patients were analyzed for the presence of enterovirus using in situ hybridization (ISH), RT-PCR, and immunohistochemistry. The presence of virus was compared with inflammatory markers such as infiltrating T cells, HLA-DR expression, and transglutaminase 2-targeted IgA deposits. Enterovirus RNA was found in diabetic patients more frequently than in control subjects and was associated with a clear inflammation response in the gut mucosa. Viral RNA was often detected in the absence of viral protein, suggesting defective replication of the virus. Patients remained virus positive in follow-up samples taken after 12 months' observation. The results suggest that a large proportion of type 1 diabetic patients have prolonged/persistent enterovirus infection associated with an inflammation process in gut mucosa. This finding opens new opportunities for studying the viral etiology of type 1 diabetes. PMID- 22315305 TI - Reversal of type 1 diabetes in mice by brown adipose tissue transplant. AB - Current therapies for type 1 diabetes (T1D) involve insulin replacement or transplantation of insulin-secreting tissue, both of which suffer from numerous limitations and complications. Here, we show that subcutaneous transplants of embryonic brown adipose tissue (BAT) can correct T1D in streptozotocin-treated mice (both immune competent and immune deficient) with severely impaired glucose tolerance and significant loss of adipose tissue. BAT transplants result in euglycemia, normalized glucose tolerance, reduced tissue inflammation, and reversal of clinical diabetes markers such as polyuria, polydipsia, and polyphagia. These effects are independent of insulin but correlate with recovery of the animals' white adipose tissue. BAT transplants lead to significant increases in adiponectin and leptin, but with levels that are static and not responsive to glucose. Pharmacological blockade of the insulin receptor in BAT transplant mice leads to impaired glucose tolerance, similar to what is seen in nondiabetic animals, indicating that insulin receptor activity plays a role in the reversal of diabetes. One possible candidate for activating the insulin receptor is IGF-1, whose levels are also significantly elevated in BAT transplant mice. Thus, we propose that the combined action of multiple adipokines establishes a new equilibrium in the animal that allows for chronic glycemic control without insulin. PMID- 22315306 TI - Gene expression differences in skin fibroblasts in identical twins discordant for type 1 diabetes. AB - Clinical studies suggest metabolic memory to hyperglycemia. We tested whether diabetes leads to persistent systematic in vitro gene expression alterations in patients with type 1 diabetes (T1D) compared with their monozygotic, nondiabetic twins. Microarray gene expression was determined in skin fibroblasts (SFs) of five twin pairs cultured in high glucose (HG) for ~6 weeks. The Exploratory Visual Analysis System tested group differences in gene expression levels within KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. An overabundance of differentially expressed genes was found in eight pathways: arachidonic acid metabolism (P = 0.003849), transforming growth factor-beta signaling (P = 0.009167), glutathione metabolism (P = 0.01281), glycosylphosphatidylinositol anchor (P = 0.01949), adherens junction (P = 0.03134), dorsal-ventral axis formation (P = 0.03695), proteasome (P = 0.04327), and complement and coagulation cascade (P = 0.04666). Several genes involved in epigenetic mechanisms were also differentially expressed. All differentially expressed pathways and all the epigenetically relevant differentially expressed genes have previously been related to HG in vitro or to diabetes and its complications in animal and human studies. However, this is the first in vitro study demonstrating diabetes relevant gene expression differences between T1D-discordant identical twins. These SF gene expression differences, persistent despite the HG in vitro conditions, likely reflect "metabolic memory", and discordant identical twins thus represent an excellent model for studying diabetic epigenetic processes in humans. PMID- 22315307 TI - Heat shock protein 60 as a mediator of adipose tissue inflammation and insulin resistance. AB - The stress protein heat shock protein 60 (Hsp60) induces secretion of proinflammatory mediators from murine adipocytes. This study aimed to study Hsp60 as a mediator of adipose tissue inflammation and skeletal muscle cell (SkMC) insulin sensitivity and to quantify plasma Hsp60 concentrations in lean and obese individuals. Regulation of Hsp60 release and Hsp60-induced cytokine secretion and signaling was measured in human adipocytes and SkMCs. Adipocytes exhibited higher Hsp60 release than preadipocytes and SkMCs, which was further stimulated by cytokines and Toll-like receptor (TLR)-4 activation. Hsp60 activated extracellular signal-related kinase (ERK)-1/2, Jun NH(2)-terminal kinase (JNK), p38, nuclear factor (NF)-kappaB, and impaired insulin-stimulated Akt phosphorylation in adipocytes. Furthermore, Hsp60 stimulated adipocytes to secrete tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8. In SkMCs, Hsp60 activated ERK1/2, JNK, and NF-kappaB and inhibits insulin signaling and insulin-stimulated glucose uptake. SkMCs released IL-6, IL-8, and monocyte chemoattractant protein-1 on Hsp60 stimulation. Plasma Hsp60 was higher in obese males than in lean males and correlated positively with BMI, blood pressure, leptin, and homeostasis model assessment-insulin resistance. In summary, Hsp60 is released by human adipocytes, increased in plasma of obese humans, and induces insulin resistance. This is accompanied by activation of proinflammatory signaling in human adipocytes and SkMCs. Thus, Hsp60 might be a factor underlying adipose tissue inflammation and obesity-associated metabolic disorders. PMID- 22315308 TI - Glycemic control and cardiovascular mortality in hemodialysis patients with diabetes: a 6-year cohort study. AB - Previous observational studies using differing methodologies have yielded inconsistent results regarding the association between glycemic control and outcomes in diabetic patients receiving maintenance hemodialysis (MHD). We examined mortality predictability of A1C and random serum glucose over time in a contemporary cohort of 54,757 diabetic MHD patients (age 63 +/- 13 years, 51% men, 30% African Americans, 19% Hispanics). Adjusted all-cause death hazard ratio (HR) for baseline A1C increments of 8.0-8.9, 9.0-9.9, and >=10%, compared with 7.0-7.9% (reference), was 1.06 (95% CI 1.01-1.12), 1.05 (0.99-1.12), and 1.19 (1.12-1.28), respectively, and for time-averaged A1C was 1.11 (1.05-1.16), 1.36 (1.27-1.45), and 1.59 (1.46-1.72). A symmetric increase in mortality also occurred with time-averaged A1C levels in the low range (6.0-6.9%, HR 1.05 [95% CI 1.01-1.08]; 5.0-5.9%, 1.08 [1.04-1.11], and <=5%, 1.35 [1.29-1.42]) compared with 7.0-7.9% in fully adjusted models. Adjusted all-cause death HR for time averaged blood glucose 175-199, 200-249, 250-299, and >=300 mg/dL, compared with 150-175 mg/dL (reference), was 1.03 (95% CI 0.99-1.07), 1.14 (1.10-1.19), 1.30 (1.23-1.37), and 1.66 (1.56-1.76), respectively. Hence, poor glycemic control (A1C >=8% or serum glucose >=200 mg/dL) appears to be associated with high all cause and cardiovascular death in MHD patients. Very low glycemic levels are also associated with high mortality risk. PMID- 22315309 TI - Rising incidence of type 1 diabetes is associated with altered immunophenotype at diagnosis. AB - The incidence of type 1 diabetes has increased rapidly over recent decades, particularly in young children. We aimed to determine whether this rise was associated with changes in patterns of humoral islet autoimmunity at diagnosis. Autoantibodies to insulin (IAA), GAD (GADA), islet antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A) were measured by radioimmunoassay in sera collected from children and young adults with newly diagnosed type 1 diabetes between 1985 and 2002. The influence of date of diagnosis on prevalence and level of autoantibodies was investigated by logistic regression with adjustment for age and HLA class II genetic risk. Prevalence of IA-2A and ZnT8A increased significantly over the period studied, and this was mirrored by raised levels of IA-2A, ZnT8A, and IA-2beta autoantibodies (IA-2betaA). IAA and GADA prevalence and levels did not change. Increases in IA-2A, ZnT8A, and IA-2betaA at diagnosis during a period of rising incidence suggest that the process leading to type 1 diabetes is now characterized by a more intense humoral autoimmune response. Understanding how changes in environment or lifestyle alter the humoral autoimmune response to islet antigens should help explain why the incidence of type 1 diabetes is increasing and may suggest new strategies for preventing disease. PMID- 22315310 TI - Loss of both ABCA1 and ABCG1 results in increased disturbances in islet sterol homeostasis, inflammation, and impaired beta-cell function. AB - Cellular cholesterol homeostasis is important for normal beta-cell function. Disruption of cholesterol transport by decreased function of the ATP-binding cassette (ABC) transporter ABCA1 results in impaired insulin secretion. Mice lacking beta-cell ABCA1 have increased islet expression of ABCG1, another cholesterol transporter implicated in beta-cell function. To determine whether ABCA1 and ABCG1 have complementary roles in beta-cells, mice lacking ABCG1 and beta-cell ABCA1 were generated and glucose tolerance, islet sterol levels, and beta-cell function were assessed. Lack of both ABCG1 and beta-cell ABCA1 resulted in increased fasting glucose levels and a greater impairment in glucose tolerance compared with either ABCG1 deletion or loss of ABCA1 in beta-cells alone. In addition, glucose-stimulated insulin secretion was decreased and sterol accumulation increased in islets lacking both transporters compared with those isolated from knockout mice with each gene alone. Combined deficiency of ABCA1 and ABCG1 also resulted in significant islet inflammation as indicated by increased expression of interleukin-1beta and macrophage infiltration. Thus, lack of both ABCA1 and ABCG1 induces greater defects in beta-cell function than deficiency of either transporter individually. These data suggest that ABCA1 and ABCG1 each make complimentary and important contributions to beta-cell function by maintaining islet cholesterol homeostasis in vivo. PMID- 22315311 TI - Thiazolidinedione treatment decreases oxidative stress in spontaneously hypertensive heart failure rats through attenuation of inducible nitric oxide synthase-mediated lipid radical formation. AB - The current study was designed to test the hypothesis that inducible nitric oxide synthase (iNOS)-mediated lipid free radical overproduction exists in an insulin resistant rat model and that reducing the accumulation of toxic metabolites is associated with improved insulin signaling and metabolic response. Lipid radical formation was detected by electron paramagnetic resonance spectroscopy with in vivo spin trapping in an obese rat model, with or without thiazolidinedione treatment. Lipid radical formation was accompanied by accumulation of toxic end products in the liver, such as 4-hydroxynonenal and nitrotyrosine, and was inhibited by the administration of the selective iNOS inhibitor 1400 W. The model showed impaired phosphorylation of the insulin signaling pathway. Ten-day rosiglitazone injection not only improved the response to an oral glucose tolerance test and corrected insulin signaling but also decreased iNOS levels. Similar to the results with specific iNOS inhibition, thiazolidinedione dramatically decreased lipid radical formation. We demonstrate a novel mechanism where a thiazolidinedione treatment can reduce oxidative stress in this model through reducing iNOS-derived lipid radical formation. Our results suggest that hepatic iNOS expression may underlie the accumulation of lipid end products and that reducing the accumulation of toxic lipid metabolites contributes to a better redox status in insulin-sensitive tissues. PMID- 22315312 TI - Genetic predisposition to dyslipidemia and type 2 diabetes risk in two prospective cohorts. AB - Dyslipidemia has been associated with type 2 diabetes, but it remains unclear whether dyslipidemia plays a causal role in type 2 diabetes. We aimed to examine the association between the genetic predisposition to dyslipdemia and type 2 diabetes risk. The current study included 2,447 patients with type 2 diabetes and 3,052 control participants of European ancestry from the Nurses' Health Study and the Health Professionals Follow-up Study. Genetic predisposition to dyslipidemia was estimated by three genotype scores of lipids (LDL cholesterol, HDL cholesterol, and triglycerides) on the basis of the established loci for blood lipids. Linear relation analysis indicated that the HDL cholesterol and triglyceride genotype scores, but not the LDL cholesterol genotype score, were linearly related to elevated type 2 diabetes risk. Each point of the HDL cholesterol and triglyceride genotype scores was associated with a 3% (odds ratio [OR] 1.03 [95% CI 1.01-1.04]) and a 2% (1.02 [1.00-1.04]) increased risk of developing type 2 diabetes, respectively. The ORs were 1.39 (1.17-1.65) and 1.19 (1.01-1.41) for type 2 diabetes by comparing extreme quartiles of the HDL cholesterol genotype score and triglyceride genotype score, respectively. In conclusion, genetic predisposition to low HDL cholesterol or high triglycerides is related to elevated type 2 diabetes risk. PMID- 22315313 TI - Optimal elevation of beta-cell 11beta-hydroxysteroid dehydrogenase type 1 is a compensatory mechanism that prevents high-fat diet-induced beta-cell failure. AB - Type 2 diabetes ultimately results from pancreatic beta-cell failure. Abnormally elevated intracellular regeneration of glucocorticoids by the enzyme 11beta hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in fat or liver may underlie pathophysiological aspects of the metabolic syndrome. Elevated 11beta-HSD1 is also found in pancreatic islets of obese/diabetic rodents and is hypothesized to suppress insulin secretion and promote diabetes. To define the direct impact of elevated pancreatic beta-cell 11beta-HSD1 on insulin secretion, we generated beta cell-specific, 11beta-HSD1-overexpressing (MIP-HSD1) mice on a strain background prone to beta-cell failure. Unexpectedly, MIP-HSD1(tg/+) mice exhibited a reversal of high fat-induced beta-cell failure through augmentation of the number and intrinsic function of small islets in association with induction of heat shock, protein kinase A, and extracellular signal-related kinase and p21 signaling pathways. 11beta-HSD1(-/-) mice showed mild beta-cell impairment that was offset by improved glucose tolerance. The benefit of higher beta-cell 11beta HSD1 exhibited a threshold because homozygous MIP-HSD1(tg/tg) mice and diabetic Lep(db/db) mice with markedly elevated beta-cell 11beta-HSD1 levels had impaired basal beta-cell function. Optimal elevation of beta-cell 11beta-HSD1 represents a novel biological mechanism supporting compensatory insulin hypersecretion rather than exacerbating metabolic disease. These findings have immediate significance for current therapeutic strategies for type 2 diabetes. PMID- 22315314 TI - Catalase deficiency accelerates diabetic renal injury through peroxisomal dysfunction. AB - Mitochondrial reactive oxygen species (ROS) play an important role in diabetes complications, including diabetic nephropathy (DN). Plasma free fatty acids (FFAs) as well as glucose are increased in diabetes, and peroxisomes and mitochondria participate in FFA oxidation in an interconnected fashion. Therefore, we investigated whether deficiency of catalase, a major peroxisomal antioxidant, accelerates DN through peroxisomal dysfunction and abnormal renal FFA metabolism. Diabetes was induced by multiple injections of low-dose streptozotocin into catalase knock-out (CKO) and wild-type (WT) C57BL/6 mice. Murine mesangial cells (MMCs) transfected with catalase small interfering RNA followed by catalase overexpression were used to further elucidate the role of endogenous catalase. Despite equivalent hyperglycemia, parameters of DN, along with markers of oxidative stress, were more accelerated in diabetic CKO mice than in diabetic WT mice up to 10 weeks of diabetes. CKO mice and MMCs showed impaired peroxisomal/mitochondrial biogenesis and FFA oxidation. Catalase deficiency increased mitochondrial ROS and fibronectin expression in response to FFAs, which were effectively restored by catalase overexpression or N-acetylcysteine. These data provide unprecedented evidence that FFA-induced peroxisomal dysfunction exacerbates DN and that endogenous catalase plays an important role in protecting the kidney from diabetic stress through maintaining peroxisomal and mitochondrial fitness. PMID- 22315315 TI - Cannabinoid 1 receptor promotes cardiac dysfunction, oxidative stress, inflammation, and fibrosis in diabetic cardiomyopathy. AB - Endocannabinoids and cannabinoid 1 (CB(1)) receptors have been implicated in cardiac dysfunction, inflammation, and cell death associated with various forms of shock, heart failure, and atherosclerosis, in addition to their recognized role in the development of various cardiovascular risk factors in obesity/metabolic syndrome and diabetes. In this study, we explored the role of CB(1) receptors in myocardial dysfunction, inflammation, oxidative/nitrative stress, cell death, and interrelated signaling pathways, using a mouse model of type 1 diabetic cardiomyopathy. Diabetic cardiomyopathy was characterized by increased myocardial endocannabinoid anandamide levels, oxidative/nitrative stress, activation of p38/Jun NH(2)-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs), enhanced inflammation (tumor necrosis factor-alpha, interleukin-1beta, cyclooxygenase 2, intracellular adhesion molecule 1, and vascular cell adhesion molecule 1), increased expression of CB(1), advanced glycation end product (AGE) and angiotensin II type 1 receptors (receptor for advanced glycation end product [RAGE], angiotensin II receptor type 1 [AT(1)R]), p47(phox) NADPH oxidase subunit, beta-myosin heavy chain isozyme switch, accumulation of AGE, fibrosis, and decreased expression of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA2a). Pharmacological inhibition or genetic deletion of CB(1) receptors attenuated the diabetes-induced cardiac dysfunction and the above-mentioned pathological alterations. Activation of CB(1) receptors by endocannabinoids may play an important role in the pathogenesis of diabetic cardiomyopathy by facilitating MAPK activation, AT(1)R expression/signaling, AGE accumulation, oxidative/nitrative stress, inflammation, and fibrosis. Conversely, CB(1) receptor inhibition may be beneficial in the treatment of diabetic cardiovascular complications. PMID- 22315316 TI - Nicotine induces negative energy balance through hypothalamic AMP-activated protein kinase. AB - Smokers around the world commonly report increased body weight after smoking cessation as a major factor that interferes with their attempts to quit. Numerous controlled studies in both humans and rodents have reported that nicotine exerts a marked anorectic action. The effects of nicotine on energy homeostasis have been mostly pinpointed in the central nervous system, but the molecular mechanisms controlling its action are still not fully understood. The aim of this study was to investigate the effect of nicotine on hypothalamic AMP-activated protein kinase (AMPK) and its effect on energy balance. Here we demonstrate that nicotine-induced weight loss is associated with inactivation of hypothalamic AMPK, decreased orexigenic signaling in the hypothalamus, increased energy expenditure as a result of increased locomotor activity, increased thermogenesis in brown adipose tissue (BAT), and alterations in fuel substrate utilization. Conversely, nicotine withdrawal or genetic activation of hypothalamic AMPK in the ventromedial nucleus of the hypothalamus reversed nicotine-induced negative energy balance. Overall these data demonstrate that the effects of nicotine on energy balance involve specific modulation of the hypothalamic AMPK-BAT axis. These targets may be relevant for the development of new therapies for human obesity. PMID- 22315317 TI - The role of FOXO and PPAR transcription factors in diet-mediated inhibition of PDC activation and carbohydrate oxidation during exercise in humans and the role of pharmacological activation of PDC in overriding these changes. AB - High-fat feeding inhibits pyruvate dehydrogenase complex (PDC)-controlled carbohydrate (CHO) oxidation, which contributes to muscle insulin resistance. We aimed to reveal molecular changes underpinning this process in resting and exercising humans. We also tested whether pharmacological activation of PDC overrides these diet-induced changes. Healthy males consumed a control diet (CD) and on two further occasions an isocaloric high-fat diet (HFD). After each diet, subjects cycled for 60 min after intravenous infusion with saline (CD and HFD) or dichloroacetate (HFD+DCA). Quadriceps muscle biopsies obtained before and after 10 and 60 min of exercise were used to estimate CHO use, PDC activation, and mRNAs associated with insulin, fat, and CHO signaling. Compared with CD, HFD increased resting pyruvate dehydrogenase kinase 2 (PDK2), PDK4, forkhead box class O transcription factor 1 (FOXO1), and peroxisome proliferator-activated receptor transcription factor alpha (PPARalpha) mRNA and reduced PDC activation. Exercise increased PDC activation and whole-body CHO use in HFD, but to a lower extent than in CD. Meanwhile PDK4 and FOXO1, but not PPARalpha or PDK2, mRNA remained elevated. HFD+DCA activated PDC throughout and restored whole-body CHO use during exercise. FOXO1 appears to play a role in HFD-mediated muscle PDK4 upregulation and inhibition of PDC and CHO oxidation in humans. Also, pharmacological activation of PDC restores HFD-mediated inhibition of CHO oxidation during exercise. PMID- 22315318 TI - Germline TRAV5D-4 T-cell receptor sequence targets a primary insulin peptide of NOD mice. AB - There is accumulating evidence that autoimmunity to insulin B chain peptide, amino acids 9-23 (insulin B:9-23), is central to development of autoimmune diabetes of the NOD mouse model. We hypothesized that enhanced susceptibility to autoimmune diabetes is the result of targeting of insulin by a T-cell receptor (TCR) sequence commonly encoded in the germline. In this study, we aimed to demonstrate that a particular Valpha gene TRAV5D-4 with multiple junction sequences is sufficient to induce anti-islet autoimmunity by studying retrogenic mouse lines expressing alpha-chains with different Valpha TRAV genes. Retrogenic NOD strains expressing Valpha TRAV5D-4 alpha-chains with many different complementarity determining region (CDR) 3 sequences, even those derived from TCRs recognizing islet-irrelevant molecules, developed anti-insulin autoimmunity. Induction of insulin autoantibodies by TRAV5D-4 alpha-chains was abrogated by the mutation of insulin peptide B:9-23 or that of two amino acid residues in CDR1 and 2 of the TRAV5D-4. TRAV13-1, the human ortholog of murine TRAV5D-4, was also capable of inducing in vivo anti-insulin autoimmunity when combined with different murine CDR3 sequences. Targeting primary autoantigenic peptides by simple germline-encoded TCR motifs may underlie enhanced susceptibility to the development of autoimmune diabetes. PMID- 22315319 TI - miR-33a modulates ABCA1 expression, cholesterol accumulation, and insulin secretion in pancreatic islets. AB - Changes in cellular cholesterol affect insulin secretion, and beta-cell-specific deletion or loss-of-function mutations in the cholesterol efflux transporter ATP binding cassette transporter A1 (ABCA1) result in impaired glucose tolerance and beta-cell dysfunction. Upregulation of ABCA1 expression may therefore be beneficial for the maintenance of normal islet function in diabetes. Studies suggest that microRNA-33a (miR-33a) expression inversely correlates with ABCA1 expression in hepatocytes and macrophages. We examined whether miR-33a regulates ABCA1 expression in pancreatic islets, thereby affecting cholesterol accumulation and insulin secretion. Adenoviral miR-33a overexpression in human or mouse islets reduced ABCA1 expression, decreased glucose-stimulated insulin secretion, and increased cholesterol levels. The miR-33a-induced reduction in insulin secretion was rescued by cholesterol depletion by methyl-beta-cyclodextrin or mevastatin. Inhibition of miR-33a expression in apolipoprotein E knockout islets and ABCA1 overexpression in beta-cell-specific ABCA1 knockout islets rescued normal insulin secretion and reduced islet cholesterol. These findings confirm the critical role of beta-cell ABCA1 in islet cholesterol homeostasis and beta-cell function and highlight modulation of beta-cell miR-33a expression as a means to influence insulin secretion. PMID- 22315320 TI - Bioactives of Artemisia dracunculus L. mitigate the role of ceramides in attenuating insulin signaling in rat skeletal muscle cells. AB - Ectopic lipids in peripheral tissues have been implicated in attenuating insulin action in vivo. The botanical extract of Artemisia dracunculus L. (PMI 5011) improves insulin action, yet the precise mechanism is not known. We sought to determine whether the mechanism by which PMI 5011 improves insulin signaling is through regulation of lipid metabolism. After differentiation, cells were separately preincubated with free fatty acids (FFAs) and ceramide C2, and the effects on glycogen content, insulin signaling, and ceramide profiles were determined. The effect of PMI 5011 on ceramide accumulation and ceramide-induced inhibition of insulin signaling was evaluated. FFAs resulted in increased levels of total ceramides and ceramide species in L6 myotubes. Saturated FFAs and ceramide C2 inhibited insulin-stimulated phosphorylation of protein kinase B/Akt and reduced glycogen content. PMI 5011 had no effect on ceramide formation or accumulation but increased insulin sensitivity via restoration of Akt phosphorylation. PMI 5011 also attenuated the FFA-induced upregulation of a negative inhibitor of insulin signaling, i.e., protein tyrosine phosphatase 1B (PTP1B), and increased phosphorylation of PTP1B. PMI 5011 attenuates the reduction in insulin signaling induced by ceramide accumulation, but the mechanism of improved insulin signaling is independent of ceramide formation. PMID- 22315321 TI - Markedly decreased blood perfusion of pancreatic islets transplanted intraportally into the liver: disruption of islet integrity necessary for islet revascularization. AB - Experimental studies indicate low revascularization of intraportally transplanted islets. This study aimed to quantify, for the first time, the blood perfusion of intrahepatically transplanted islets and elucidate necessary factors for proper islet graft revascularization at this site. Yellow chameleon protein 3.0 islets expressing fluorescent protein in all cells were transplanted. Graft blood perfusion was determined by microspheres. The vascular density and relative contribution of donor blood vessels in revascularization was evaluated using islets expressing green fluorescent protein under the Tie-2 promoter. Blood perfusion of intrahepatic islets was as a mean only 5% of that of native islets at 1-month posttransplantation. However, there was a marked heterogeneity where blood perfusion was less decreased in islets transplanted without prior culture and in many cases restored in islets with disrupted integrity. Analysis of vascular density showed that distorted islets were well revascularized, whereas islets still intact at 1-month posttransplantation were almost avascular. Few donor endothelial cells were observed in the new islet vasculature. The very low blood perfusion of intraportally transplanted islets is likely to predispose for ischemia and hamper islet function. Since donor endothelial cells do not expand posttransplantation, disruption of islet integrity is necessary for revascularization to occur by recipient blood vessels. PMID- 22315322 TI - Evidence for early defects in insulin sensitivity and secretion before the onset of glucose dysregulation in obese youths: a longitudinal study. AB - We sought to determine whether obese adolescents with high-"normal" 2-h post-oral glucose tolerance test glucose levels display defects in insulin secretion and sensitivity associated with future development of impaired glucose tolerance (IGT). Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and insulin secretion by applying mathematical modeling during the hyperglycemic clamp in 60 normal glucose tolerance (NGT) obese adolescents, divided into three groups based on the 2-h glucose values (<100, 100-119, 120-139 mg/dL), and in 21 IGT obese adolescents. Glucose tolerance was reevaluated after 2 years. Insulin sensitivity decreased significantly across 2-h glucose NGT categories, while the highest NGT category and IGT group were similar. First-phase insulin secretion decreased across NGT categories, while no difference was found between the highest NGT group and IGT subjects. Second-phase secretion was similar across all NGT and IGT groups. The disposition index ((C)DI) decreased across NGT categories, while no difference was observed between the highest NGT and IGT subjects. Age and (C)DI were the best predictors of 2-h glucose after two years. Across rising categories of normal 2-h glucose levels, NGT obese adolescents exhibit significant impairment of beta-cell function relative to insulin sensitivity associated with the development of IGT. PMID- 22315323 TI - Effects of non-HLA gene polymorphisms on development of islet autoimmunity and type 1 diabetes in a population with high-risk HLA-DR,DQ genotypes. AB - We assessed the effects of non-HLA gene polymorphisms on the risk of islet autoimmunity (IA) and progression to type 1 diabetes in the Diabetes Autoimmunity Study in the Young. A total of 1,743 non-Hispanic, white children were included: 861 first-degree relatives and 882 general population children identified as having high-risk HLA-DR/DQ genotypes for type 1 diabetes. Of those, 109 developed IA and 61 progressed to diabetes. Study participants were genotyped for 20 non HLA polymorphisms, previously confirmed as type 1 diabetes susceptibility loci. PTPN22 and UBASH3A predicted both IA and diabetes in regression models controlling for family history of type 1 diabetes and presence of HLA-DR3/4 DQB1*0302 genotype. In addition, PTPN2 predicted IA whereas INS predicted type 1 diabetes. The final multivariate regression models for both IA and type 1 diabetes included PTPN22, UBASH3A, and INS, in addition to family history of type 1 diabetes and HLA-DR3/4. In general population children, the most frequent combinations including these five significant predictors conferred hazard ratio of up to 13 for IA and >40 for type 1 diabetes. Non-HLA susceptibility alleles may help estimate risk for development of type 1 diabetes in the general population. These findings require replication in different populations. PMID- 22315324 TI - Age-related impairment in insulin release: the essential role of beta(2) adrenergic receptor. AB - In this study, we investigated the significance of beta(2)-adrenergic receptor (beta(2)AR) in age-related impaired insulin secretion and glucose homeostasis. We characterized the metabolic phenotype of beta(2)AR-null C57Bl/6N mice (beta(2)AR( /-)) by performing in vivo and ex vivo experiments. In vitro assays in cultured INS-1E beta-cells were carried out in order to clarify the mechanism by which beta(2)AR deficiency affects glucose metabolism. Adult beta(2)AR(-/-) mice featured glucose intolerance, and pancreatic islets isolated from these animals displayed impaired glucose-induced insulin release, accompanied by reduced expression of peroxisome proliferator-activated receptor (PPAR)gamma, pancreatic duodenal homeobox-1 (PDX-1), and GLUT2. Adenovirus-mediated gene transfer of human beta(2)AR rescued these defects. Consistent effects were evoked in vitro both upon beta(2)AR knockdown and pharmacologic treatment. Interestingly, with aging, wild-type (beta(2)AR(+/+)) littermates developed impaired insulin secretion and glucose tolerance. Moreover, islets from 20-month-old beta(2)AR(+/+) mice exhibited reduced density of beta(2)AR compared with those from younger animals, paralleled by decreased levels of PPARgamma, PDX-1, and GLUT2. Overexpression of beta(2)AR in aged mice rescued glucose intolerance and insulin release both in vivo and ex vivo, restoring PPARgamma/PDX-1/GLUT2 levels. Our data indicate that reduced beta(2)AR expression contributes to the age related decline of glucose tolerance in mice. PMID- 22315325 TI - Hepatic TRAF2 regulates glucose metabolism through enhancing glucagon responses. AB - Obesity is associated with intrahepatic inflammation that promotes insulin resistance and type 2 diabetes. Tumor necrosis factor receptor-associated factor (TRAF)2 is a key adaptor molecule that is known to mediate proinflammatory cytokine signaling in immune cells; however, its metabolic function remains unclear. We examined the role of hepatic TRAF2 in the regulation of insulin sensitivity and glucose metabolism. TRAF2 was deleted specifically in hepatocytes using the Cre/loxP system. The mutant mice were fed a high-fat diet (HFD) to induce insulin resistance and hyperglycemia. Hepatic glucose production (HGP) was examined using pyruvate tolerance tests, (2)H nuclear magnetic resonance spectroscopy, and in vitro HGP assays. The expression of gluconeogenic genes was measured by quantitative real-time PCR. Insulin sensitivity was analyzed using insulin tolerance tests and insulin-stimulated phosphorylation of insulin receptors and Akt. Glucagon action was examined using glucagon tolerance tests and glucagon-stimulated HGP, cAMP-responsive element-binding (CREB) phosphorylation, and expression of gluconeogenic genes in the liver and primary hepatocytes. Hepatocyte-specific TRAF2 knockout (HKO) mice exhibited normal body weight, blood glucose levels, and insulin sensitivity. Under HFD conditions, blood glucose levels were significantly lower (by >30%) in HKO than in control mice. Both insulin signaling and the hypoglycemic response to insulin were similar between HKO and control mice. In contrast, glucagon signaling and the hyperglycemic response to glucagon were severely impaired in HKO mice. In addition, TRAF2 overexpression significantly increased the ability of glucagon or a cAMP analog to stimulate CREB phosphorylation, gluconeogenic gene expression, and HGP in primary hepatocytes. These results suggest that the hepatic TRAF2 cell autonomously promotes hepatic gluconeogenesis by enhancing the hyperglycemic response to glucagon and other factors that increase cAMP levels, thus contributing to hyperglycemia in obesity. PMID- 22315326 TI - Tracheal intubation in the critically ill: a multi-centre national study of practice and complications. AB - BACKGROUND: Complications associated with tracheal intubation may occur in up to 40% of critically ill patients. Since practice in emergency airway management varies between intensive care units (ICUs) and countries, complication rates may also differ. We undertook a prospective, observational study of tracheal intubation performed by critical care doctors in Scotland to identify practice, complications, and training. METHODS: For 4 months, we collected data on any intubation performed by doctors working in critical care throughout Scotland except those in patients having elective surgery and those carried out before admission to hospital. We used a standardized data form to collect information on pre-induction physical state and organ support, the doctor carrying out the intubation, the techniques and drugs used, and complications noted. RESULTS: Data from 794 intubations were analysed. Seventy per cent occurred in ICU and 18% occurred in emergency departments. The first-time intubation success rate was 91%, no patient required more than three attempts at intubation, and one patient required surgical tracheostomy. Severe hypoxaemia ( <80%) occurred in 22%, severe hypotension (systolic arterial pressure <80 mm Hg) in 20%, and oesophageal intubation in 2%. Three-quarters of intubations were performed by doctors with more than 24 months formal anaesthetic training and all but one doctor with <6 months training had senior supervision. CONCLUSIONS: Tracheal intubation by critical care doctors in Scotland has a higher first-time success rate than described in previous reports of critical care intubation, and technical complications are few. Doctors carrying out intubation had undergone longer formal training in anaesthesia than described previously, and junior trainees are routinely supervised. Despite these good results, further work is necessary to reduce physiological complications and patient morbidity. PMID- 22315327 TI - Secondary spread of caudal block as assessed by ultrasonography. AB - BACKGROUND: Redistribution and secondary spread after the initial injection of local anaesthetics (LAs) are important factors that contribute to the final spread of caudal block in children. However, to date, these phenomena have yet not been studied in detail. Thus, the aim of this observational study was to define patterns of secondary spread and redistribution of a caudal block by means of real-time ultrasonography scanning and cutaneous testing. METHODS: Ultrasound assessment of LA spread within the caudal-epidural space and epidural pressure was followed during 15 min after initial injection (1.5 ml kg(-1), ropivacaine 0.2%) in 16 infants. At 15 min post-injection, cutaneous testing was also performed to assess the cranial dermatomal level of the block (at end-tidal sevoflurane 2.5%). RESULTS: The median ultrasound-assessed cranial spread was Th10 and Th8 at 0 and 15 min, respectively, and the sensory level at 15 min was Th4. The caudal injection was initially found to compress the terminal part of the dural sac, later followed by a partial re-expansion as epidural pressure was returning towards pre-injection values. An intrasegmental redistribution from the dorsal to the ventral compartment of the epidural space was also observed. CONCLUSIONS: Two separate patterns of secondary spread of caudal block could be observed, being horizontal intrasegmental redistribution and longitudinal cranial spread. The observed bi-directional movement of cerebrospinal fluid (coined 'the CSF rebound mechanism') does explain a major part of the difference between the initial ultrasound-assessed cranial level and the final level determined by cutaneous testing. PMID- 22315328 TI - Ultrasound assessment of cranial spread during caudal blockade in children: effect of the speed of injection of local anaesthetics. AB - BACKGROUND: Despite caudal blockade being the most widely used regional anaesthetic procedure for infants and children undergoing subumbilical surgery, the question whether the injection velocity of the local anaesthetic itself affects its spread in the epidural space has not yet been investigated. Thus, the aim of the present study was to measure the cranial spread of caudally administered local anaesthetics in infants and children by means of real-time ultrasonography, with a special focus on comparing the effect of using two different speeds of injection. METHODS: Fifty ASA I-II infants and children, aged up to 6 yr, weighing up to 25 kg, undergoing subumbilical surgery, were enrolled in this prospective, randomized, observer-blinded study. Caudal blockade was performed under ultrasound observation using ropivacaine 1 ml kg(-1) 0.2% or 0.35% and an injection given at either 0.25 ml s(-1) or 0.5 ml s(-1), respectively. RESULTS: Ultrasound observation of the local anaesthetic flow and the extent of cranial spread was possible in all patients. All caudal blocks were considered successful, and all surgical procedures could be completed without any indications of insufficient analgesia. No statistically significant difference could be observed between the two injection speeds regarding the cranial spread of the local anaesthetic in the epidural space. CONCLUSIONS: The main finding of the present study is that the speed of injection of the local anaesthetic does not affect its cranial spread during caudal blockade in infants and children. Therefore, the prediction of the cranial spread of the local anaesthetic, depending on the injection speed, is not possible. PMID- 22315329 TI - Rapid sequence induction and intubation with rocuronium-sugammadex compared with succinylcholine: a randomized trial. AB - BACKGROUND: An unanticipated difficult airway may arise during rapid sequence induction and intubation (RSII). The aim of the trial was to assess how rapidly spontaneous ventilation could be re-established after RSII. We hypothesized that the time period from tracheal intubation to spontaneous ventilation would be shorter with rocuronium-sugammadex than with succinylcholine. METHODS: This randomized and patient- and observer-blinded trial was approved by the regional Ethics Committee and the Danish Medicines Agency. We included elective surgical patients undergoing general anaesthesia for RSII using alfentanil (10 ug kg(-1)), propofol (2 mg kg(-1)), and either succinylcholine (1 mg kg(-1)) or rocuronium (1 mg kg(-1)). Sugammadex (16 mg kg(-1)) was given in the rocuronium group after tracheal intubation. The primary endpoint was the time from correct placement of the tracheal tube to spontaneous ventilation, defined as a respiratory rate of more than 8 bpm and a tidal volume of at least 3 ml kg(-1) for 30 s. RESULTS: We included 61 patients; of whom, 55 were evaluated for the primary endpoint. The median time from tracheal intubation to spontaneous ventilation was 406 s with succinylcholine and 216 s with rocuronium-sugammadex (P = 0.002). The median time from tracheal intubation to 90% recovery of the first twitch in train-of-four (T(1) 90%) was 518 s with succinylcholine and 168 s with rocuronium-sugammadex (P < 0.0001). Intubation conditions and time to tracheal intubation were not significantly different. CONCLUSIONS: RSII with rocuronium followed by reversal with sugammadex allowed earlier re-establishment of spontaneous ventilation than with succinylcholine. PMID- 22315330 TI - Desflurane-induced post-conditioning against myocardial infarction is mediated by calcium-activated potassium channels: role of the mitochondrial permeability transition pore. AB - BACKGROUND: Desflurane (DES)-induced preconditioning is mediated by large conductance calcium-activated potassium channels (BK(Ca)). Whether BK(Ca) are involved in anaesthetic-induced post-conditioning is unknown. We tested the hypothesis that DES-induced post-conditioning is mediated by BK(Ca) upstream of the mitochondrial permeability transition pore (mPTP). METHODS: Pentobarbital anaesthetized male C57Black/6 mice were subjected to 45 min coronary artery occlusion (CAO) and 3 h reperfusion. Animals received either no intervention or dimethylsulphoxide (DMSO, 10 ul g(-1)). DES (1.0 MAC, 7.5 vol%) was administered for 18 min, starting 3 min before the end of CAO. The following agents were given either alone or in combination with DES: the BK(Ca) activator NS1619 (1 ug g( 1)), the BK(Ca) inhibitor iberiotoxin (IbTx, 0.05 ug g(-1)), the mPTP opener atractyloside (ATRA, 25 ug g(-1)), and the mPTP inhibitor cyclosporine A (CYC A, 10 ug g(-1)). Infarct size (IS) was determined with triphenyltetrazolium chloride and the area at risk with Evans Blue, respectively. RESULTS: IS in control animals was 48(6)%. Neither DMSO, IbTx nor ATRA affected myocardial IS. DES alone or NS1619 alone or the combination reduced IS (P<0.05), CYC A alone or in combination with IbTx or DES also reduced IS (P<0.05). DES-induced reduction of myocardial IS was completely abolished by IbTx and was partially blocked by ATRA and ATRA partially blocked IS reduction by NS1619. CONCLUSIONS: These data suggest that DES-induced post-conditioning against myocardial infarction is mediated by BK(Ca) and mPTP. Cardioprotection by BK(Ca) activator NS1619 might occur, at least in part, independently of mPTP. PMID- 22315331 TI - Effect of sugammadex or neostigmine neuromuscular block reversal on bispectral index monitoring of propofol/remifentanil anaesthesia. AB - BACKGROUND: Sugammadex is a modified gamma-cyclodextrin with a novel mechanism of action for reversing the steroidal neuromuscular blocking agent rocuronium. Bispectral index (BIS) is an EEG-derived measure which can be sensitive to frontal electromyographic (EMG) artifacts. We compared BIS values before and after sugammadex or neostigmine neuromuscular block (NMB) reversal in patients with or without high EMG activity. METHODS: During stable propofol/remifentanil anaesthesia and rocuronium-induced block, 48 patients were randomly allocated to receive sugammadex 4 mg kg(-1) or neostigmine 50 MUg kg(-1)/glycopyrrolate 10 MUg kg(-1), 10 min after the end of surgery. RESULTS: Five minutes after sugammadex administration, mean BIS 50.1 (10.3) increased (P=0.018) to 61.7 (7.9) in 11 patients with high EMG activity. In contrast, BIS 49.3 (4.9) remained at 51.9 (5.4) in 13 patients who had no EMG activity. Fifteen minutes after neostigmine administration, mean BIS 51.9 (8.1) increased (P=0.007) to 63.9 (8.1) in 13 patients who had reappearance of muscle activity. However, in 11 patients who had no EMG activity, BIS 52.3 (7.4) remained at 53.3 (6.8). There was no significant difference between the sugammadex and neostigmine groups over time. CONCLUSIONS: We have shown that reversal of NMB with sugammadex or neostigmine increased BIS values dependent on the presence of EMG activity. Thus, the effect of muscle activity reappearance during rocuronium NMB reversal spuriously increasing the BIS value should be taken into consideration when relying on BIS monitoring for evaluating propofol/remifentanil recovery. PMID- 22315332 TI - Preclinical disposition of GDC-0973 and prospective and retrospective analysis of human dose and efficacy predictions. AB - [3,4-Difluoro-2-(2-fluoro-4-iodo-phenylamino)-phenyl]-((S)-3-hydroxy-3-piperidin 2-yl-azetidin-1-yl)-methanone (GDC-0973) is a potent and highly selective inhibitor of mitogen-activated protein kinase(MAPK)/extracellular signal regulated kinase (ERK) 1/2 (MEK1/2), a MAPK kinase that activates ERK1/2. The objectives of these studies were to characterize the disposition of GDC-0973 in preclinical species and to determine the relationship of GDC-0973 plasma concentrations to efficacy in Colo205 mouse xenograft models. The clearance (CL) of GDC-0973 was moderate in mouse (33.5 ml . min(-1) . kg(-1)), rat (37.9 +/- 7.2 ml . min(-1) . kg(-1)), and monkey (29.6 +/- 8.5 ml . min(-1) . kg(-1)). CL in dog was low (5.5 +/- 0.3 ml . min(-1) . kg(-1)). The volume of distribution across species was large, 6-fold to 15-fold body water; half-lives ranged from 4 to 13 h. Protein binding in mouse, rat, dog, monkey, and human was high, with percentage unbound, 1 to 6%. GDC-0973-related radioactivity was rapidly and extensively distributed to tissues; however, low concentrations were observed in the brain. In rats and dogs, [(14)C]GDC-0973 was well absorbed (fraction absorbed, 70-80%). The majority of [(14)C]GDC-0973-related radioactivity was recovered in the bile of rat (74-81%) and dog (65%). The CL and volume of distribution of GDC-0973 in human, predicted by allometry, was 2.9 ml . min(-1) . kg(-1) and 9.9 l/kg, respectively. The predicted half-life was 39 h. To characterize the relationship between plasma concentration of GDC-0973 and tumor growth inhibition, pharmacokinetic-pharmacodynamic modeling was applied using an indirect response model. The KC(50) value for tumor growth inhibition in Colo205 xenografts was estimated to be 0.389 MUM, and the predicted clinical efficacious dose was ~10 mg. Taken together, these data are useful in assessing the disposition of GDC-0973, and where available, comparisons with human data were made. PMID- 22315333 TI - An investigation of the catalytic activity of CYP2A13*4 with coumarin and polymorphisms of CYP2A13 in a Chinese Han population. AB - CYP2A13 has been identified as an efficient catalyst for the metabolisms of coumarin, aflatoxin B(1) (AFB(1)), and several tobacco-specific carcinogens. The reported CYP2A13 polymorphisms with missense variations have been studied for their functional consequences, and CYP2A13*4 (R101Q) variant was found to be a null enzyme in metabolizing 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), AFB(1), and 5-methoxypsoralen. In the present study, CYP2A13*4 was expressed in Sf9 cells and evaluated for coumarin 7-hydroxylation activity. Our results demonstrated that CYP2A13*4 showed no activity in coumarin 7-hydroxylation. Furthermore, computer modeling studies were conducted to probe the mechanisms underlying the loss of catalytic activity of CYP2A13*4. The results suggested that the R101Q alteration may result in the absence of several hydrogen bonds involved in heme binding and thus lead to the loss of function in CYP2A13*4. In addition, for the first time, the distribution frequencies of all eight known CYP2A13 missense alleles were examined in a Chinese Han population. The distribution frequencies of CYP2A13*3 allele and CYP2A13*4 allele in the Chinese Han population were statistically significantly different from the reported values in Japanese. Considering that the two variants of CYP2A13 are incapable of metabolic activation of NNK and AFB(1), the susceptibility to NNK or AFB(1) exposure between the Chinese Han population and Japanese can be different. PMID- 22315335 TI - Influenza vaccines: more options and more opportunities. PMID- 22315334 TI - Draft genome of the pearl oyster Pinctada fucata: a platform for understanding bivalve biology. AB - The study of the pearl oyster Pinctada fucata is key to increasing our understanding of the molecular mechanisms involved in pearl biosynthesis and biology of bivalve molluscs. We sequenced ~1150-Mb genome at ~40-fold coverage using the Roche 454 GS-FLX and Illumina GAIIx sequencers. The sequences were assembled into contigs with N50 = 1.6 kb (total contig assembly reached to 1024 Mb) and scaffolds with N50 = 14.5 kb. The pearl oyster genome is AT-rich, with a GC content of 34%. DNA transposons, retrotransposons, and tandem repeat elements occupied 0.4, 1.5, and 7.9% of the genome, respectively (a total of 9.8%). Version 1.0 of the P. fucata draft genome contains 23 257 complete gene models, 70% of which are supported by the corresponding expressed sequence tags. The genes include those reported to have an association with bio-mineralization. Genes encoding transcription factors and signal transduction molecules are present in numbers comparable with genomes of other metazoans. Genome-wide molecular phylogeny suggests that the lophotrochozoan represents a distinct clade from ecdysozoans. Our draft genome of the pearl oyster thus provides a platform for the identification of selection markers and genes for calcification, knowledge of which will be important in the pearl industry. PMID- 22315336 TI - Safety and long-term humoral immune response in adults after vaccination with an H1N1 2009 pandemic influenza vaccine with or without AS03 adjuvant. AB - BACKGROUND: In this study (NCT00985088) we evaluated different formulations of an H1N1 2009 pandemic influenza vaccine that deliver various viral hemagglutinin (HA) doses with or without AS03 (a tocopherol-based oil-in-water adjuvant system). METHODS: A total of 1340 healthy subjects aged >=18 years were randomized to receive 1 or 2 doses of an adjuvanted (3.75-MUg HA/AS03(A) or 1.9 MUg HA/AS03(B)) or nonadjuvanted vaccine formulation. Safety and immunogenicity (by hemagglutination-inhibition [HI] assay) after each dose and 6 months after dose 1 are reported here. RESULTS: A single dose of AS03(A)-adjuvanted 3.75-MUg HA H1N1 2009 induced the strongest immune responses in subjects aged 18-64 years (seroprotection rate [SPR], 97.2%; seroconversion rate [SCR], 90.1%) as well as in subjects aged >64 years (SPR, 91.1%; SCR, 78.2%) 21 days after vaccination. Six months after dose 1, subjects who received 2 doses of either the adjuvanted formulation or 1 dose of the adjuvanted 3.75-MUg HA formulation continued to meet all Center for Biologics Evaluation and Research and Committee for Medicinal Products for Human Use criteria. All formulations had clinically acceptable safety profiles. CONCLUSION: A single dose of the 3.75-MUg HA AS03(A)-adjuvanted H1N1 2009 influenza vaccine was highly immunogenic in both age strata (18-64 and >64 years), inducing long-term persistence of the immune response until at least 6 months after dose 1. PMID- 22315343 TI - Propranolol reduced volume, colour and elevation of infantile haemangiomas. PMID- 22315344 TI - 15 minute consultation: a structured approach to the management of facial paralysis in a child. AB - OBJECTIVE: To present a structured approach for an outpatient consultation of a child with facial paralysis. METHOD: Review of literature and description of approach followed in our unit. CONCLUSION: A focused history and examination is key to establish the cause and draw a management plan for paediatric facial paralysis. PMID- 22315345 TI - Mid-term follow-up after transcatheter aortic valve implantation. PMID- 22315346 TI - A novel clinical method for quantification of regional left ventricular pressure strain loop area: a non-invasive index of myocardial work. AB - AIMS: Left ventricular (LV) pressure-strain loop area reflects regional myocardial work and metabolic demand, but the clinical use of this index is limited by the need for invasive pressure. In this study, we introduce a non invasive method to measure LV pressure-strain loop area. METHODS AND RESULTS: Left ventricular pressure was estimated by utilizing the profile of an empiric, normalized reference curve which was adjusted according to the duration of LV isovolumic and ejection phases, as defined by timing of aortic and mitral valve events by echocardiography. Absolute LV systolic pressure was set equal to arterial pressure measured invasively in dogs (n = 12) and non-invasively in patients (n = 18). In six patients, myocardial glucose metabolism was measured by positron emission tomography (PET). First, we studied anaesthetized dogs and observed an excellent correlation (r = 0.96) and a good agreement between estimated LV pressure-strain loop area and loop area by LV micromanometer and sonomicrometry. Secondly, we validated the method in patients with various cardiac disorders, including LV dyssynchrony, and confirmed an excellent correlation (r = 0.99) and a good agreement between pressure-strain loop areas using non-invasive and invasive LV pressure. Non-invasive pressure-strain loop area reflected work when incorporating changes in local LV geometry (r = 0.97) and showed a strong correlation with regional myocardial glucose metabolism by PET (r = 0.81). CONCLUSIONS: The novel non-invasive method for regional LV pressure-strain loop area corresponded well with invasive measurements and with directly measured myocardial work and it reflected myocardial metabolism. This method for assessment of regional work may be of clinical interest for several patients groups, including LV dyssynchrony and ischaemia. PMID- 22315347 TI - Consistency test of the cell cycle: roles for p53 and EGR1. AB - Mammalian cells are constantly exposed to multiple mitogens and, hence, have developed machineries that help them ignore fortuitous signals. In a recent report in Molecular Cell, we highlighted the molecular details of such a noise reduction filter, including roles for EGR1, AKT, and p53. Brief exposure to a mitogen drives formation of inhibitory p53-chromatin complexes, which are disabled only if the growth factor is still present several hours later. We propose that this "consistency test" prevents repeated division cycles of normal cells but might become defective in most cancer cells. PMID- 22315349 TI - Concomitant tumor resistance: the role of tyrosine isomers in the mechanisms of metastases control. AB - Concomitant tumor resistance (CR) is a phenomenon in which a tumor-bearing host is resistant to the growth of secondary tumor implants and metastasis. Although previous studies indicated that T-cell-dependent processes mediate CR in hosts bearing immunogenic small tumors, manifestations of CR induced by immunogenic and nonimmunogenic large tumors have been associated with an elusive serum factor. In a recently published study, we identified this factor as meta-tyrosine and ortho tyrosine, 2 isomers of tyrosine that would not be present in normal proteins. In 3 different murine models of cancer that generate CR, both meta- and ortho tyrosine inhibited tumor growth. Additionally, we showed that both isoforms of tyrosine blocked metastasis in a fourth model that does not generate CR but is sensitive to CR induced by other tumors. Mechanistic studies showed that the antitumor effects of the tyrosine isomers were mediated in part by early inhibition of the MAP/ERK pathway and inactivation of STAT3, potentially driving tumor cells into a state of dormancy in G(0)-phase. Other mechanisms, putatively involving the activation of an intra-S-phase checkpoint, would also inhibit tumor proliferation by accumulating cells in S-phase. By revealing a molecular basis for the classical phenomenon of CR, our findings may stimulate new generalized approaches to limit the development of metastases that arise after resection of primary tumors or after other stressors that may promote the escape of metastases from dormancy, an issue that is of pivotal importance to oncologists and their patients. PMID- 22315351 TI - A universal strategy for adoptive immunotherapy of cancer through use of a novel T-cell antigen receptor. AB - Adoptive immunotherapies composed of T cells engineered to express a chimeric antigen receptor (CAR) offer an attractive strategy for treatment of human cancer. However, CARs have a fixed antigen specificity such that only one tumor associated antigen (TAA) can be targeted, limiting the efficacy that can be achieved because of heterogeneous TAA expression. For this reason, a more generalized and effective application of CAR therapy would benefit from the capability to produce large panels of CARs against many known TAAs. In this study, we show a novel strategy to extend the recognition specificity potential of a bioengineered lymphocyte population, allowing flexible approaches to redirect T cells against various TAAs. Our strategy employs a biotin-binding immune receptor (BBIR) composed of an extracellular-modified avidin linked to an intracellular T-cell signaling domain. BBIR T cells recognized and bound exclusively to cancer cells pretargeted with specific biotinylated molecules. The versatility afforded by BBIRs permitted sequential or simultaneous targeting of a combination of distinct antigens. Together, our findings show that a platform of universal T-cell specificity can significantly extend conventional CAR approaches, permitting the tailored generation of T cells of unlimited antigen specificity for improving the effectiveness of adoptive T-cell immunotherapies for cancer. PMID- 22315352 TI - Oncolytic virus and anti-4-1BB combination therapy elicits strong antitumor immunity against established cancer. AB - Oncolytic virotherapy using vaccinia virus (Vv) has shown some encouraging antitumor responses in mouse models and patients, but the breadth of efficacy in clinical trials has been somewhat limited. Given that antitumor effects have correlated with increased host immune responses, we hypothesized that improved therapeutic outcomes may be achieved by using oncolytic virus (OV) in combination with a potent immune agonist reagent. In this study, we carried out a preclinical evaluation of a genetically engineered strain of oncolytic vaccinia virus (Vvdd) for its capacity to induce antitumor responses when combined with an agonist antibody (Ab) specific for the costimulatory molecule 4-1BB (CD137). In immune competent syngeneic mouse models of cancer, this combination therapy significantly reduced the growth of established subcutaneous tumors relative to either treatment alone. Importantly, the development of pulmonary metastatic lesions was also reduced. Tumor growth inhibition was associated with increased numbers of CD11b(+) and CD11c(+) myeloid cells in the tumor draining lymph nodes, greater infiltration of CD8(+) effector T and natural killer (NK) cells, and a more sustained presence of neutrophils at the tumor site. Depletion of T or NK cells or neutrophils reduced efficacy, confirming their contribution to an effective therapeutic response. We further extended this conclusion through results from IFNgamma-deficient mice. In summary, our findings offered a proof-of concept for a combinatorial approach to enhance the antitumor efficacy of an OV, suggesting a strategy to improve their use as an immunotherapeutic treatment for cancer. PMID- 22315353 TI - The glue crisis in surgery of acute aortic dissection type A is ongoing. PMID- 22315354 TI - Gastric distension is a contributing factor to pneumonia after pulmonary resection. AB - OBJECTIVES: The literature concerning relations between thoracic surgery and digestive motility is poor. The aim of our study was two-fold: (i) to show a link between thoracic surgery and gastric distension and (ii) between post-operative pneumoniae and gastric distension. METHODS: A retrospective analysis was conducted in 262 patients who had undergone a thoracotomy for lung resection between January and December 2007. Transverse diameter of the stomach was measured on chest X-rays performed on Day 0 and on Day 1. Gastric distension was defined as a ratio (R) D1/D0 higher than 1.3 (min: 0.5; max: 4.1). Three groups were defined: Group 1 (absence of distension) R < 1.3; Group 2 (moderate distension) 1.3 <= R < 2.3; Group 3 (major distension) R >= 2.3. International criteria of the Center of Disease Control were used to define pneumonia. Appropriate statistical tests were carried out. RESULTS: There were 73 women (27.9%) and 189 men (72.1%), ages ranged from 20 to 83 years (average: 59.9 years). As for gastric distension, 194 patients (74.04%) constituted Group 1, 53 (20.23%) Group 2 and 15 (5.73%) Group 3. Pneumonectomy significantly increased the incidence of gastric distension on Day 1 (P = 0.04). The side, mediastinal lymphadenectomy and personal medical past history of upper gastro-intestinal tract surgery had no statistically significant influence on the incidence of gastric distension. Univariate analysis showed that patients with gastric distension on D1 had significantly more infectious pneumonia on Day 5 (P < 0.0001): 16 (8.25%) patients in Group 1, vs 14 (26.41%) in Group 2 and 7 (46.67%) in Group 3. Furthermore, on Day 5, 33.33% (n = 8) of pneumectomies had pneumonia, against 12.18% (n = 29) of patients who had undergone another type of surgery (P = 0.01). On multivariate analysis, gastric distension was an independent predictive factor of infectious pneumonia on Day 5 (Group 3: odds ratio = 16.127 [4.267; 60 959], P < 0.0001). CONCLUSIONS: We established, in our cohort of patients, a link between pneumonectomy and gastric distension on Day 1 and infectious pneumonia on Day 5. A prospective multicentre study would be desirable to verify these data. PMID- 22315355 TI - Left ventricular septal perforation after apico-aortic conduit. PMID- 22315356 TI - Validation of a thoracoscopic lobectomy simulator. AB - OBJECTIVES: Although simulation is considered integral to general surgery training, its role has only recently been recognized in thoracic surgical education, perhaps due to a lack of widely available, validated simulators for advanced thoracic procedures. This study evaluates the construct, content and face validity of an inexpensive, easily reproducible simulator for teaching thoracoscopic lobectomy. METHODS: Construct validity (ability of the simulator to discriminate between users of different skill levels) was assessed by having surgical trainees perform a lobectomy on the simulator. Participants were divided into three groups (experienced, intermediate and novice) based on self-reported experience with minimally invasive surgery. After instruction and practice time to limit the effect of any simulator-specific learning curve, each performed a left upper lobectomy that was scored using a standardized assessment tool incorporating total time plus weighted penalty minutes assigned for errors. Content validity (simulator requires same steps and decision-making as a clinical lobectomy) was assessed using a Likert scale by those participants who had previously seen a thoracoscopic lobectomy in a patient. RESULTS: Thirty-one residents participated in the study (12 experienced, 6 intermediate and 13 novice). All 12 experienced participants completed the lobectomy. The other groups were less successful with 4 of 6 in the intermediate group and 5 of 13 in the novice group completing the lobectomy (P = 0.004). The mean times for lobectomy + penalty minutes were 35 + 6.8 (experienced), 50 + 13 (intermediate) and 54 + 20 (novice). Differences between groups were statistically significant for experienced vs. novice (P < 0.001) and experienced vs. intermediate (P < 0.04). Content validity was assessed by the 18 participants who had previously seen a thoracoscopic lobectomy with a mean of 9.2 of 10 possible points. CONCLUSIONS: The thoracoscopic lobectomy simulator used in this study demonstrates acceptable validity and can be a useful tool for teaching thoracoscopic lobectomy to trainees or experienced surgeons. PMID- 22315357 TI - Aortic coaptation in repair. PMID- 22315358 TI - Early clinical and haemodynamic results after aortic valve replacement with the Freedom SOLO bioprosthesis (experience of Italian multicenter study). AB - OBJECTIVES: The present study investigates early clinical and haemodynamic results with the Freedom SOLO bioprosthesis (FSB) for aortic valve replacement (AVR) in eight Italian institutions. METHODS: From 2004 to 2008, a total of 229 patients [139 females (60.7%); mean age 74 +/- 8 years, left ventricular (LV) ejection fraction >40%] underwent AVR with FSB. One hundred and four patients underwent preoperatively, at 1-3 and at 12 months after AVR resting transthoracic echocardiography with the effective orifice area index (EOAi) assessment, peak and mean transvalvular pressure gradients and the LV mass index (LVMi) measurement. A subset of 34 patients underwent exercise stress echocardiography at a mean of 9.6 months after AVR. RESULTS: Post-operative mortality was 3.1%. At 1-3 months, FSB showed a significant increase in the EOAi (0.39 +/- 0.17 to 1.04 +/- 0.17 cm(2)/m(2); P < 0.0001), a reduction in the mean gradient (43.2 +/- 16.9 to 4.3 +/- 2.3 mmHg; P < 0.0001) and a significant regression of the LVMi (147.6 +/- 30.5 to 121.6 +/- 27.4 g/m(2); P < 0.0001). During exercise stress echocardiography, the mean aortic gradients increased from 4.4 +/- 1.7 at rest to 7.0 +/- 2.7 mmHg at peak stress (P < 0.001). The EOA increased from 1.74 +/- 0.33 to 1.80 +/- 0.36 cm(2) (P = 0.0291). Mean gradients at peak stress had better correlation with resting EOAi (r = -0.74; P < 0.001) than with the prosthesis size (r = 0.43; P = 0.01). CONCLUSIONS: The supra-annular implantation of FSB offers excellent haemodynamic performance both at rest and during exercise and is associated with the rapid regression of the LV. PMID- 22315359 TI - A novel germline inactivating mutation in the CASR gene in an Italian kindred affected by familial hypocalciuric hypercalcemia. AB - OBJECTIVE: Familial hypocalciuric hypercalcemia (FHH) syndrome is a rare benign condition, inherited as an autosomal dominant trait, in which inactivating mutations of the calcium-sensing receptor (CASR) gene affects the body's ability to regulate calcium homeostasis. Its outcome is featured by increased levels of serum calcium, moderate hypophosphatemia, and inadequately normal or elevated circulating parathyroid hormone levels. Affected patients are mostly asymptomatic and do not benefit from surgical resection of their mildly enlarged parathyroids. DESIGN: We evaluated for hypercalcemia an Italian family that was identified via a young adult male proband referred to our center for parathyroidectomy. METHODS: The patients and the family members were evaluated both biochemically and genetically as suspected FHH subjects. An in vitro functional study was performed by site-directed mutagenesis, and CASR activity was monitored by measuring intracellular calcium ([Ca(2)(+)](i)). RESULTS: The patient had a novel germline heterozygous CASR mutation (c.361_364GATT; p.D121del/fsX122). The mutation caused a premature stop codon at codon 122, exiting a truncated protein. The biochemical phenotype of all family members carrying the heterozygous deletion was concordant with classic FHH syndrome. CONCLUSIONS: Our findings confirm the role of CASR gene mutational analysis to offer a valuable addition for the recognition of FHH in hypercalcemic patients not yet characterized for a positive familial history of hypercalcemia, the only condition that identifies CASR gene mutations in hypercalcemia. PMID- 22315360 TI - Choosing the right cell: guidance with three-dimensional optical coherence tomography of bifurcational stenting. PMID- 22315361 TI - Echocardiographic assessment of diastolic biventricular properties in patients operated for severe pulmonary regurgitation and association with exercise capacity. AB - AIMS: We aimed to assess the impact of surgical pulmonary valve replacement (PVR) for severe pulmonary regurgitation (PR) on biventricular function and its effect on exercise capacity. METHODS AND RESULTS: Seventy-three patients (mean age 23.6+/-11.5 years, 47 females) underwent surgical PVR for PR. Echocardiogram and magnetic resonance imaging to assess ventricular size and function, and a cardiopulmonary exercise test were performed before, and 1-year post-surgery. Median New York Heart Association class improved from 2 to 1 but peak oxygen uptake (VO2) did not change. Left ventricular (LV) cardiac output increased from 3.2+/-0.9 to 3.5+/-0.7 L/min (P=0.003). However, this was not associated with increased trans-mitral velocities (?E=-0.13, P=0.004; ?A=0.03, P=0.395), or increased heart rate (-0.002%, P=0.993). Trans-tricuspid rapid right ventricular (RV) filling increased significantly, whereas early diastolic myocardial velocity in RV wall decreased (E velocity: 0.57+/-0.14-0.65+/-0.21, P=0.034; and E/e' from 6.7+/-1.9 to 14.8+/-7.0, P<0.0001). RV and LV late diastolic velocities and their ratio to early velocities (A, a', E/A, and e'/a') correlated with pre- and/or post-PVR peak VO2. No correlations were found between indexes of systolic function and peak VO2, either before or after surgery. Doppler evidence of restrictive RV physiology resolved after elimination of PR. CONCLUSION: Surgical PVR for PR improves RV filling and increases left ventricular stroke volume, however, this could not be demonstrated by conventional Doppler echocardiography. Diastolic ventricular function was associated with exercise capacity. Because of its load dependency, E/e' ratio failed in assessing diastolic function. Pre systolic flow in pulmonary trunk in presence of severe PR does not determine intrinsic myocardial stiffness. PMID- 22315362 TI - The United States Preventive Services Task Force recommendation against prostate specific antigen screening--point. PMID- 22315363 TI - The United States Preventive Services Task Force recommendation against prostate specific antigen screening--counterpoint. PMID- 22315364 TI - Prostate cancer risk in men with baseline history of coronary artery disease: results from the REDUCE Study. AB - BACKGROUND: Coronary artery disease (CAD) and prostate cancer (PCa) are not only common diseases, but share many risk factors. To date, only a few studies have explored the relationship between CAD and PCa risk, with conflicting results. METHODS: The four-year REDUCE study tested dutasteride 0.5 mg daily for PCa risk reduction in men with prostate specific antigen (PSA) of 2.5 to 10.0 ng/mL and a negative biopsy. Among men who underwent at least one on-study biopsy (n = 6,729; 82.8%), the association between CAD and overall PCa risk and disease grade was examined with logistic and multinomial logistic regression adjusting for clinicopathologic features, respectively. RESULTS: Overall, 547 men (8.6%) had a history of CAD. Men with CAD were significantly older and had higher body mass index, PSA, and larger prostate volumes and were more likely to have diabetes, hypertension, and hypercholesterolemia and take aspirin and statins. On multivariate analysis, CAD was associated with a 35% increased risk of PCa diagnosis (OR = 1.35, 95% CI: 1.08-1.67, P = 0.007), while elevating risk of both low- (OR = 1.34, 95% CI: 1.05-1.73, P = 0.02) and high-grade disease (OR = 1.34, 95% CI: 0.95-1.88, P = 0.09). CONCLUSIONS: In a post hoc hypothesis developing secondary analysis of the REDUCE study, CAD was significantly associated with increased PCa diagnosis. IMPACT: If confirmed in other studies, this suggests CAD may be a novel PCa risk factor and suggests common shared etiologies. Whether lifestyle changes shown to reduce CAD risk (i.e., weight loss, exercise, cholesterol reduction, etc.) can reduce PCa risk, warrants further study. PMID- 22315365 TI - Milk and dairy consumption among men with prostate cancer and risk of metastases and prostate cancer death. AB - BACKGROUND: Whether milk and dairy intake after a prostate cancer diagnosis is associated with a poorer prognosis is unknown. We investigated postdiagnostic milk and dairy intake in relation to risk of lethal prostate cancer (metastases and prostate cancer death) among participants in the Health Professionals Follow Up Study. METHODS: The cohort consisted of 3,918 men diagnosed with apparently localized prostate cancer between 1986 and 2006, and followed to 2008. Data on milk and dairy intake were available from repeated questionnaires. We used Cox proportional hazards models to calculate HRs and 95% CIs of the association between postdiagnostic milk and dairy intake and prostate cancer outcomes. RESULTS: We ascertained 229 prostate cancer deaths and an additional 69 metastases during follow-up. In multivariate analysis, total milk and dairy intakes after diagnosis were not associated with a greater risk of lethal prostate cancer. Men with the highest versus lowest intake of whole milk were at an increased risk of progression (HR = 2.15, 95% CI: 1.28-3.60; P(trend) < 0.01). Men in the highest versus lowest quintile of low-fat dairy intake were at a decreased risk of progression (HR = 0.62; 95% CI: 0.40-0.95; P(trend) = 0.07). CONCLUSIONS: With the exception of whole milk, our results suggest that milk and dairy intake after a prostate cancer diagnosis is not associated with an increased risk of lethal prostate cancer. IMPACT: This is the first larger prospective study investigating the relation between postdiagnostic milk and dairy intake and risk of lethal prostate cancer. PMID- 22315366 TI - Night shift work and hormone levels in women. AB - BACKGROUND: Night shift work may disrupt the normal nocturnal rise in melatonin, resulting in increased breast cancer risk, possibly through increased reproductive hormone levels. We investigated whether night shift work is associated with decreased levels of urinary 6-sulfatoxymelatonin, the primary metabolite of melatonin, and increased urinary reproductive hormone levels. METHODS: Participants were 172 night shift and 151 day shift-working nurses, aged 20-49 years, with regular menstrual cycles. Urine samples were collected throughout work and sleep periods and assayed for 6-sulfatoxymelatonin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estrone conjugate (E1C). RESULTS: 6-Sulfatoxymelatonin levels were 62% lower and FSH and LH were 62% and 58% higher, respectively, in night shift-working women during daytime sleep than in day shift-working women during nighttime sleep (P <= 0.0001). Nighttime sleep on off-nights was associated with 42% lower 6 sulfatoxymelatonin levels among the night shift workers, relative to the day shift workers (P < 0.0001); no significant differences in LH or FSH were observed. 6-Sulfatoxymelatonin levels during night work were approximately 69% lower and FSH and LH were 35% and 38% higher, compared with day shift workers during nighttime sleep. No differences in E1C levels between night and day shift workers were observed. Within night shift workers, 6-sulfatoxymelatonin levels were lower and reproductive hormone levels were higher during daytime sleep and nighttime work, relative to nighttime sleep (P < 0.05). CONCLUSIONS: These results indicate that night shift workers have substantially reduced 6 sulfatoxymelatonin levels during night work and daytime sleep and that levels remain low even when a night shift worker sleeps at night. IMPACT: Shift work could be an important risk factor for many other cancers in addition to breast cancer. PMID- 22315367 TI - Aberrant vimentin methylation is characteristic of upper gastrointestinal pathologies. AB - BACKGROUND: We have previously established aberrant DNA methylation of vimentin exon-1 (VIM methylation) as a common epigenetic event in colon cancer and as a biomarker for detecting colon neoplasia. We now examine vimentin methylation in neoplasia of the upper gastrointestinal tract. METHODS: Using a quantitative real time methylation-specific PCR assay, we tested for vimentin methylation in archival specimens of esophageal and gastric neoplasia. RESULTS: We find that acquisition of aberrant vimentin methylation is highly common in these neoplasms, but largely absent in controls. The highest frequency of vimentin methylation was detected in lesions of the distal esophagus, including 91% of Barrett's esophagus (n = 11), 100% of high-grade dysplasia (HGD, n = 5), and 81% of esophageal adenocarcinoma (EAC, n = 26) but absent in controls (n = 9). Vimentin methylation similarly was detected in 87% of signet ring (n = 15) and 53% of intestinal type gastric cancers (n = 17). Moreover, in tests of cytology brushings vimentin methylation proved detectable in 100% of Barrett's esophagus cases (n = 7), 100% of HGD cases (n = 4), and 83% of EAC cases (n = 18) but was absent in all controls (n = 5). CONCLUSIONS: These findings establish aberrant vimentin methylation as a highly common epigenetic alteration in neoplasia of the upper gastrointestinal tract and show that Barrett's esophagus, even without dysplasia, already contains epigenetic alterations characteristic of adenocarcinoma. IMPACT: These findings suggest vimentin methylation as a biomarker of upper gastrointestinal neoplasia with potential for development as molecular cytology in esophageal screening. PMID- 22315368 TI - Aromatic DNA adducts and risk of gastrointestinal cancers: a case-cohort study within the EPIC-Spain. AB - BACKGROUND: Colorectal (CRC) and gastric cancer (GC) are associated with meat intake and tobacco smoke, maybe because of aromatic compounds occurring in tobacco smoking and formed during cooking meat. Activated metabolites of these compounds may bind to DNA forming bulky adducts. METHODS: Forty-eight subjects diagnosed of GC and 154 of CRC during a 7-year follow-up period in the European Prospective Investigation into Cancer and Nutrition-Spain cohort were compared with a sample of 296 subjects using a case-cohort approach. Aromatic adducts to DNA from leukocytes collected at recruitment were measured by means of the (32)P postlabeling technique. The relative risk (RR) and 95% confidence interval (CI), adjusted by relevant confounders were estimated by a modified version of Cox regression. RESULTS: Using the log(2)-transformed adduct concentration, we observed a RR = 1.57 (CI: 1.25-1.97) for CRC, which means a 57% increased risk associated with doubling the level of adducts, and 47% (RR = 1.47, CI: 1.07-2.00) increase in risk of GC. The association was more marked for colon than for rectal tumors. CONCLUSIONS: The level of aromatic adducts in the DNA is independently associated with an increased risk of gastric and CRCs. This effect could be due to aromatic compounds present in tobacco smoke or formed in meat, but they could be also due to genotoxic compounds from other sources. IMPACT: Sources of aromatic compounds should be taken into account, in addition to known risk factors, in the research and prevention of tumors of the stomach, colon, and rectum. PMID- 22315376 TI - The value of science in integration of services. PMID- 22315377 TI - Effect of the Expanded Program on Immunization Contact Method of data collection on health behaviors in Mali. AB - BACKGROUND: The Expanded Program on Immunization Contact Method (EPI-CM) is a proposed monitoring and program management tool for developing countries. The method involves health workers tallying responses to questions about health behaviors during routine immunizations and providing targeted counseling. We evaluated whether asking caretakers about health behaviors during EPI visits led to changes in those behaviors. METHODS: We worked in 2 districts in Mali: an intervention district where during immunization visits workers asked about 4 health behaviors related to bed net use, fever, respiratory disease, and diarrhea, and a control district where workers conducted routine immunization activities without health behavior questions. To evaluate the effect of EPI-CM, we conducted a cross-sectional household survey at baseline and 1 year postintervention. We used multivariate logistic regression to compare between districts the change over 1 year in 4 health behaviors: use of insecticide treated nets, appropriate fever treatment, care-seeking for respiratory complaints, and appropriate diarrhea treatment. RESULTS: There were no significant differences between the 2 districts in the change in the 4 health behaviors when controlling for age, sex, maternal education and occupation, immunization history, and wealth. CONCLUSIONS: We found no evidence that EPI-CM increases healthy behaviors. Further evaluation of other potential benefits and costs of EPI-CM is warranted. PMID- 22315378 TI - Validity of Expanded Program on Immunization Contact Method health behavior estimates in Mali. AB - BACKGROUND: In the developing world, household surveys provide high-quality health behavior data integral to public health program management. The Expanded Program on Immunization Contact Method (EPI-CM) is a proposed, less resource intensive method in which health center staff incorporate health behavior questions into routine vaccination activities. No systematic evaluation of EPI-CM validity has yet been conducted. METHODS: We used concurrent household survey and EPI-CM to collect data on 4 infant health behaviors in Mali at 2 time points (8 total comparisons). Studied health behaviors were bednet use, obtaining care for fever, obtaining care for a respiratory complaint, and using oral rehydration solution for diarrhea. Household survey and EPI-CM estimates were considered equivalent if a 95% confidence interval about the difference in estimated proportions fell within the interval (-.10, .10). RESULTS: EPI-CM estimates were higher than household survey estimates for 7 of 8 unadjusted paired estimates; estimates of bednet use in 2009 met a priori equivalence criteria in a setting of high bednet use (90.5%). When we restricted household survey data to infants up to-date on vaccinations, estimates for behaviors other than bednet use remained substantially different. CONCLUSIONS: We were unable to demonstrate that EPI-CM, as implemented, consistently produces data comparable with household survey data. PMID- 22315379 TI - Vaccination Week in the Americas: an opportunity to integrate other health services with immunization. AB - Vaccination Week in the Americas (VWA) is an initiative of the countries and territories of the Americas that works to advance equity and access to vaccination. The initiative focuses on reaching populations with limited access to regular health services and promotes solidarity among countries. As the Expanded Program on Immunization is one of the world's best-established health programs, integrating other interventions with immunization services has been highly promoted. Using data available from the Pan American Health Organization, we explored the extent of integration of other interventions with immunization in Latin American and Caribbean (LAC) countries as part of VWA. At least 14 countries or territories have integrated other interventions with immunization during VWA. The most common integrated intervention is vitamin A supplementation, followed by deworming. However, a variety of other interventions have been integrated, such as educational activities, supplementation with vitamins and minerals, and provision of health services. Data on coverage of integrated interventions are limited. Integration of other interventions with immunization in LAC countries is widespread, and its impact and lessons learned merit further examination. PMID- 22315380 TI - Somalia: supporting the child survival agenda when routine health service is broken. AB - Somalia, one of the most unstable countries in the world, has been without a permanent government for nearly 2 decades. With a health system in total disarray, coverage of basic health interventions remains low and, maternal and child mortality is among the highest in the world. Health partners jointly outlined an integrated package of critical child survival interventions to be delivered through a population-based delivery strategy known as Child Health Days (CHDs), to reduce child mortality. Using this strategy, key child survival interventions are delivered to the community with an objective of reaching children <5 years and women of childbearing age in all districts of Somalia every 6 months. Through this strategy, immunization services were reached in remote areas, and coverage disparity between the urban and rural areas was reduced from 17% (42% urban and 25% rural) to 10% (50% urban and 60% rural). In addition, infants were reached with a third dose of diphtheria-pertussis-tetanus vaccine, achieving 51% coverage during 2009 and 66% in 2010. This paper summarizes the challenges of scaling up child interventions in the troubled context of Somalia by reviewing the planning, implementation, and achievements of CHDs as well as reflecting on challenges for the future of child survival in Somalia. PMID- 22315381 TI - Economic evaluation of a Child Health Days strategy to deliver multiple maternal and child health interventions in Somalia. AB - INTRODUCTION: Child Health Days (CHDs) are increasingly used by countries to periodically deliver multiple maternal and child health interventions as time limited events, particularly to populations not reached by routine health services. In countries with a weak health infrastructure, this strategy could be used to reach many underserved populations with an integrated package of services. In this study, we estimate the incremental costs, impact, cost effectiveness, and return on investment of 2 rounds of CHDs that were conducted in Somalia in 2009 and 2010. METHODS: We use program costs and population estimates reported by the World Health Organization and United Nations Children's Fund to estimate the average cost per beneficiary for each of 9 interventions delivered during 2 rounds of CHDs implemented during the periods of December 2008 to May 2009 and August 2009 to April 2010. Because unstable areas were unreachable, we calculated costs for targeted and accessible beneficiaries. We model the impact of the CHDs on child mortality using the Lives Saved Tool, convert these estimates of mortality reduction to life years saved, and derive the cost-effectiveness ratio and the return on investment. RESULTS: The estimated average incremental cost per intervention for each targeted beneficiary was $0.63, with the cost increasing to $0.77 per accessible beneficiary. The CHDs were estimated to save the lives of at least 10,000, or 500,000 life years for both rounds combined. The CHDs were cost-effective at $34.00/life year saved. For every $1 million invested in the strategy, an estimated 615 children's lives, or 29,500 life years, were saved. If the pentavalent vaccine had been delivered during the CHDs instead of diphtheria-pertussis-tetanus vaccine, an additional 5000 children's lives could have been saved. CONCLUSIONS: Despite high operational costs, CHDs are a very cost-effective service delivery strategy for addressing the leading causes of child mortality in a conflict setting like Somalia and compare favorably with other interventions rated as health sector "best buys" in sub-Saharan Africa. PMID- 22315382 TI - Integrated delivery of health services during outreach visits: a literature review of program experience through a routine immunization lens. AB - BACKGROUND: Outreach services are used systematically to deliver immunization and health services to individuals with insufficient access to health facilities in lower-income countries. Currently, the topic of integrated service delivery during immunization outreach lacks the attention paid to integration at fixed sites or during campaigns. This article explores integrated outreach and risks associated with service integration. METHODS: Published and gray literature in public health databases and on organization websites were reviewed, yielding 33 articles and gray literature documents for a literature review of experience integrating other services with routine immunization at outreach sessions. RESULTS: The current policy climate favors service integration as a strategy for increasing the equity and efficiency of important health interventions. However, integration may also present some risk to well-established and resourced interventions, such as immunization, which must be recognized as programs compete for limited resources. Experience reveals integration opportunities in planning and intersectoral coordination, training and supervision, community participation, pooled funding, and monitoring. CONCLUSIONS: The reviewed literature indicates that successful integration of health interventions with immunization at routine outreach sessions requires well-planned and implemented steps. It also highlights the need for additional studies or feedback on planning and implementing integrated outreach services in lower-income countries. PMID- 22315383 TI - Building on success--potential to improve coverage of multiple health interventions through integrated delivery with routine childhood vaccination. AB - BACKGROUND: Integrating delivery of nonvaccine interventions with childhood vaccinations has been suggested as a mechanism to accelerate progress toward Millennium Development Goals. METHODS: Demographic health surveys from 28 sub Saharan African countries were analyzed to determine potential coverage with 5 nonvaccine interventions that could be delivered to children, mothers, and families during routine infant vaccinations. Potential coverage levels were calculated among households with children aged 12-23 months, based on existing coverage of interventions and vaccinations. FINDINGS: Most (>60%) children in families that had not received nonvaccine interventions had been vaccinated. If nonvaccine interventions could be delivered with vaccinations, the median percentage of households owning a bed net could increase from 46% to 92% and those with improved or treated sources of water from 55% to 91%. The median percentage of children who had received vitamin A supplementation could increase from 66% to 90%. Mothers who have been tested for human immunodeficiency virus could increase from 16% to 86%. CONCLUSIONS: In Africa, vaccination programs could provide a platform to substantially increase coverage of nonvaccine interventions. Studies are needed to investigate programmatic approaches to optimize the selection, adoption, and long-term utilization of these interventions and to assess the impact on vaccination and other intervention coverage. PMID- 22315384 TI - Integrating immunization with other health interventions for greater impact: the right strategic choice. PMID- 22315385 TI - Strengthening evidence-based planning of integrated health service delivery through local measures of health intervention delivery times. AB - BACKGROUND: Immunization services in developing countries are increasingly used as platforms for delivery of other health interventions. A challenge for scaling up interventions on existing platforms is insufficient resources allocated to the integrated platform with the risk of overburdening a health worker. Determining the length of time to deliver priority interventions can be useful information in planning integrated services and mitigating this risk. We designed and tested a methodology for collecting the time needed to deliver selected interventions. METHODOLOGY: At 18 health facilities in Mali, Ethiopia, and Cameroon, we observed delivery of 11 maternal and child health interventions to determine delivery times. We interviewed health workers to estimate self-reported delivery times. RESULTS: Based on observations, vitamin A supplementation (median, 2:00 minutes per child) and vaccinations (median, 2:22 minutes) took the least amount of time to deliver, whereas human immunodeficiency virus counseling and testing and sick infant treatment interventions were among the longest to deliver. Health worker reported times to deliver interventions were consistently higher than observed times. CONCLUSIONS: Using locally-obtained data can be useful to step for planners to determine how best to use existing platforms for delivering new interventions, particularly since these interventions may require substantially more time to deliver compared to immunizations. PMID- 22315386 TI - Community and health worker perceptions and preferences regarding integration of other health services with routine vaccinations: four case studies. AB - BACKGROUND: Integration of routine vaccination and other maternal and child health services is becoming more common and the services being integrated more diverse. Yet knowledge gaps remain regarding community members and health workers acceptance, priorities, and concerns related to integration. METHODS: Qualitative health worker interviews and community focus groups were conducted in 4 African countries (Kenya, Mali, Ethiopia, and Cameroon). RESULTS: Integration was generally well accepted by both community members and health workers. Most integrated services were perceived positively by the communities, although perceptions around socially sensitive services (eg, family planning and human immunodeficiency virus) differed by country. Integration benefits reported by both community members and health workers across countries included opportunity to receive multiple services at one visit, time and transportation cost savings, increased service utilization, maximized health worker efficiency, and reduced reporting requirements. Concerns related to integration included being labor intensive, inadequate staff to implement, inadequately trained staff, in addition to a number of more broad health system issues (eg, stockouts, wait times). CONCLUSIONS: Communities generally supported integration, and integrated services may have the potential to increase service utilization and possibly even reduce the stigma of certain services. Some concerns expressed related to health system issues rather than integration, per se, and should be addressed as part of a wider approach to improve health services. Improved planning and patient flow and increasing the number and training of health staff may help to mitigate logistical challenges of integrating services. PMID- 22315387 TI - Impact of integration of hygiene kit distribution with routine immunizations on infant vaccine coverage and water treatment and handwashing practices of Kenyan mothers. AB - Integration of immunizations with hygiene interventions may improve use of both interventions. We interviewed 1361 intervention and 1139 comparison caregivers about hygiene practices and vaccination history, distributed water treatment and hygiene kits to caregivers during infant vaccination sessions in intervention clinics for 12 months, and conducted a followup survey of 2361 intervention and 1033 comparison caregivers. We observed significant increases in reported household water treatment (30% vs 44%, P < .0001) and correct handwashing technique (25% vs 51%, P < .0001) in intervention households and no changes in comparison households. Immunization coverage improved in both intervention and comparison infants (57% vs 66%, P = .04; 37% vs 53%, P < .0001, respectively). Hygiene kit distribution during routine immunizations positively impacted household water treatment and hygiene without a negative impact on vaccination coverage. Further study is needed to assess hygiene incentives, implement alternative water quality indicators, and evaluate the impact of this intervention in other settings. PMID- 22315388 TI - Experiences integrating delivery of maternal and child health services with childhood immunization programs: systematic review update. AB - BACKGROUND: The World Health Organization and the United Nations Children's Fund promote integration of maternal and child health (MCH) and immunization services as a strategy to strengthen immunization programs. We updated our previous review of integrated programs and reviewed reports of integration of MCH services with immunization programs at the service delivery level. METHODS: Published and unpublished reports of interventions integrating MCH and immunization service delivery were reviewed by searching journal databases and Web sites and by contacting organizations. RESULTS: Among 27 integrated activities, interventions included hearing screening, human immunodeficiency virus services, vitamin A supplementation, deworming tablet administration, malaria treatment, bednet distribution, family planning, growth monitoring, and health education. When reported, linked intervention coverage increased, though not to the level of the corresponding immunization coverage in all cases. Logistical difficulties, time intensive interventions ill suited for campaign delivery, concern for harming existing services, inadequate overlap of target age groups, and low immunization coverage were identified as challenges. CONCLUSIONS: Results of this review reinforce our 2005 review findings, including importance of intervention compatibility and focus on immunization program strength. Ensuring proper planning and awareness of compatibility of service delivery requirements were found to be important. The review revealed gaps in information about costs, comparison to vertical delivery, and impact on all integrated interventions that future studies should aim to address. PMID- 22315389 TI - Integration of routine vaccination and hygiene interventions: a comparison of 2 strategies in Kenya. AB - BACKGROUND: Hygiene interventions reduce child mortality from diarrhea. Vaccination visits provide a platform for delivery of other health services but may overburden nurses. We compared 2 strategies to integrate hygiene interventions with vaccinations in Kenya's Homa Bay district, 1 using community workers to support nurses and 1 using nurses. METHODS: Homa Bay was divided into 2 geographical areas, each with 9 clinics. Each area was randomly assigned to either the nurse or community-assisted strategy. At infant vaccination visits hygiene kits were distributed by the nurse or community member. Surveys pre- and post-intervention, measured hygiene indicators and vaccination coverage. Interviews and focus groups assessed acceptability. RESULTS: Between April 2009 and March 2010, 39 158 hygiene kits were distributed. Both nurse and community assisted strategies were well-accepted. Hygiene indicators improved similarly in nurse and community sites. However, residual chlorine in water changed in neither group. Vaccination coverage increased in urban areas. In rural areas coverage either remained unchanged or increased with 1 exception (13% third dose poliovirus vaccine decrease). CONCLUSIONS: Distribution of hygiene products and education during vaccination visits was found to be feasible using both delivery strategies. Additional studies should consider assessing the use of community members to support integrated service delivery. PMID- 22315390 TI - Integrating health promotion and disease prevention interventions with vaccination in Honduras. AB - OBJECTIVE: We sought to review and describe health interventions integrated with immunization delivery, both routine and during national vaccination weeks, in Honduras between 1991 and 2009. METHODS: We compiled and examined all annual evaluation reports from the national Expanded Program on Immunization and reports from the national vaccination weeks (NVWs) between 1988 and 2009. We held discussions with the persons responsible for immunization and other programs in the Health Secretary of Honduras for the same time period. RESULTS: Since 1991, several health promotion and disease prevention interventions have been integrated with immunization delivery, including vitamin A supplementation (since 1994), folic acid supplementation (2003), early detection of retinoblastoma (since 2003), breastfeeding promotion (2007-2008), and disease control activities during public health emergencies, such as cholera control (1991-1992) and dengue control activities (since 1991, when a dengue emergency coincides with the NVW). Success factors included sufficient funds and supplies to ensure sustainability and joint planning, delivery, and monitoring. CONCLUSIONS: Several health interventions have been integrated with vaccination delivery in Honduras for nearly 20 years. The immunization program in Honduras has sufficient structure, organization, acceptance, coverage, and experience to achieve successful integration with health interventions if carefully planned and suitably implemented. PMID- 22315391 TI - Pharmacovigilance of malaria intermittent preventive treatment in infants coupled with routine immunizations in 6 African countries. AB - BACKGROUND: Intermittent preventive treatment in infants (IPTi) is a new malaria control strategy coupled with the delivery of routine immunizations recommended by the World Health Organization since 2009 for countries with moderate to high endemicity. To evaluate its safety profile and identify potential new adverse events (AEs) following simultaneous administration of sulfadoxine-pyrimethamine (SP-IPTi) with immunizations, we measured AE incidence and evaluated spontaneous AE reporting. METHODS: A cohort event monitoring study was conducted on 24 000 infants in 2 countries after administration of SP-IPTi during routine immunizations. Additional pharmacovigilance training and supervision were conducted to stimulate AE passive reporting in 6 African countries. RESULTS: No serious AEs were found by active follow-up, representing 95% probability that the rate does not exceed 1 per 8000. No serious AEs were found by retrospective review of hospital registers. The rate of moderate AEs probably linked to immunization and/or SP-IPTi was 1.8 per 1000 doses (95% confidence interval, 1.50 2.00). Spontaneous reporting of AEs remained <1% of cases collected by active follow-up. CONCLUSIONS: Simultaneous administration of SP-IPTi and immunizations is a safe strategy for implementation with a low risk of serious AEs to infants. Strategies toward strengthening spontaneous reporting in Africa should include not only the provider but also beneficiaries or their caregivers. PMID- 22315392 TI - Do estimates of intervention coverage obtained from children at immunization clinics provide a reasonable approximation to population values? AB - OBJECTIVE: The purpose of this study was to determine whether the magnitude of selection bias incurred by measuring child survival intervention coverage at convenient sampling opportunities (child immunization contacts) is sufficiently small for the approach to be used as a management tool within country programs. METHODS: We estimated the magnitude of selection bias by calculating values of 13 health indicators for 31 countries using Demographic and Health Survey data for children immunized with the third dose of the diphtheria-pertussis-tetanus vaccine (DPT3) and those who were immunized with measles vaccine, and comparing their values to those obtained for the population as a whole. RESULTS: Estimates of intervention coverage derived from immunized children are close to population values if immunization coverage exceeds 60%. Levels of bias were lower for interventions that were not delivered directly by formal health services, such as use of mosquito nets among children and provision of more fluid for diarrhea. Levels of bias were also lower when using results for measles vaccine than for DPT3, suggesting that the measles vaccination contact may be the most opportune time to collect data on additional health indicators. CONCLUSIONS: The coverage of immunization programs has reached 60% in 85% of African countries, so selection bias does not appear to invalidate the measurement of intervention coverage at immunization contacts. PMID- 22315393 TI - Liver fat reduction with niacin is influenced by DGAT-2 polymorphisms in hypertriglyceridemic patients. AB - Niacin reduces plasma triglycerides, but it may increase free fatty acids and insulin resistance during long-term treatment. We examined the effect of extended release niacin on liver fat content in Chinese patients with dyslipidemia and whether the common diacylglycerol acyltransferase-2 (DGAT2) polymorphisms influenced this effect. The 39 patients (baseline liver fat content: 12.8 +/- 7.6%, triglycerides: 3.30 +/- 1.67 mmol/l) were treated with niacin, gradually increasing the dose to 2 g/day for a total of 23 weeks. The liver fat content and visceral/subcutaneous fat was measured before and after treatment. Subjects were genotyped for the DGAT2 rs3060 and rs101899116 polymorphisms. There were significant (P < 0.001) reductions in plasma triglycerides (-34.9 +/- 37.6%), liver fat content (-47.2 +/- 32.8%), and visceral fat (-6.3 +/- 15.8%, P < 0.05) after niacin treatment. Mean body weight decreased by 1.46 +/- 2.7% (1.17 +/- 2.44 kg, P < 0.001) during the study, but liver fat changes remained significant after adjustment for age, gender, and body weight changes [mean absolute change (95% CI): -6.1% (-8.0, -4.3), P < 0.001]. The DGAT2 variant alleles were associated with a smaller reduction in liver fat content in response to niacin after adjustment for other covariates (P < 0.01). These findings suggest that niacin treatment may reduce liver fat content in Chinese patients with dyslipidemia and that the mechanism may involve inhibition of DGAT2. However, the findings might have been confounded by the small but significant reductions in body weight during the study. Future large randomized controlled trials are needed to verify these findings. PMID- 22315394 TI - Fish oil increases raft size and membrane order of B cells accompanied by differential effects on function. AB - Fish oil (FO) targets lipid microdomain organization to suppress T-cell and macrophage function; however, little is known about this relationship with B cells, especially at the animal level. We previously established that a high FO dose diminished mouse B-cell lipid raft microdomain clustering induced by cross linking GM1. To establish relevance, here we tested a FO dose modeling human intake on B-cell raft organization relative to a control. Biochemical analysis revealed more docosahexaenoic acid (DHA) incorporated into phosphatidylcholines than phosphatidylethanolamines of detergent-resistant membranes, consistent with supporting studies with model membranes. Subsequent imaging experiments demonstrated that FO increased raft size, GM1 expression, and membrane order upon cross-linking GM1 relative to no cross-linking. Comparative in vitro studies showed some biochemical differences from in vivo measurements but overall revealed that DHA, but not eicosapentaenoic acid (EPA), increased membrane order. Finally, we tested the hypothesis that disrupting rafts with FO would suppress B cell responses ex vivo. FO enhanced LPS-induced B-cell activation but suppressed B-cell stimulation of transgenic naive CD4(+) T cells. Altogether, our studies with B cells support an emerging model that FO increases raft size and membrane order accompanied by functional changes; furthermore, the results highlight differences in EPA and DHA bioactivity. PMID- 22315395 TI - Insulin and AMPK regulate FA translocase/CD36 plasma membrane recruitment in cardiomyocytes via Rab GAP AS160 and Rab8a Rab GTPase. AB - The FA translocase cluster of differentiation 36 (CD36) facilitates FA uptake by the myocardium, and its surface recruitment in cardiomyocytes is induced by insulin, AMP-dependent protein kinase (AMPK), or contraction. Dysfunction of CD36 trafficking contributes to disordered cardiac FA utilization and promotes progression to disease. The Akt substrate 160 (AS160) Rab GTPase-activating protein (GAP) is a key regulator of vesicular trafficking, and its activity is modulated via phosphorylation. Our study documents that AS160 mediates insulin or AMPK-stimulated surface translocation of CD36 in cardiomyocytes. Knock-down of AS160 redistributes CD36 to the surface and abrogates its translocation by insulin or the AMPK agonist 5-aminoimidazole-4-carboxamide-1-beta-d ribofuranoside (AICAR). Conversely, overexpression of a phosphorylation-deficient AS160 mutant (AS160 4P) suppresses the stimulated membrane recruitment of CD36. The AS160 substrate Rab8a GTPase is shown via overexpression and knock-down studies to be specifically involved in insulin/AICAR-induced CD36 membrane recruitment. Our findings directly demonstrate AS160 regulation of CD36 trafficking. In myocytes, the AS160 pathway also mediates the effect of insulin, AMPK, or contraction on surface recruitment of the glucose transporter GLUT4. Thus, AS160 constitutes a point of convergence for coordinating physiological regulation of CD36 and GLUT4 membrane recruitment. PMID- 22315396 TI - Enzyme functional evolution through improved catalysis of ancestrally nonpreferred substrates. AB - In this study, we investigated the role for ancestral functional variation that may be selected upon to generate protein functional shifts using ancestral protein resurrection, statistical tests for positive selection, forward and reverse evolutionary genetics, and enzyme functional assays. Data are presented for three instances of protein functional change in the salicylic acid/benzoic acid/theobromine (SABATH) lineage of plant secondary metabolite-producing enzymes. In each case, we demonstrate that ancestral nonpreferred activities were improved upon in a daughter enzyme after gene duplication, and that these functional shifts were likely coincident with positive selection. Both forward and reverse mutagenesis studies validate the impact of one or a few sites toward increasing activity with ancestrally nonpreferred substrates. In one case, we document the occurrence of an evolutionary reversal of an active site residue that reversed enzyme properties. Furthermore, these studies show that functionally important amino acid replacements result in substrate discrimination as reflected in evolutionary changes in the specificity constant (k(cat)/K(M)) for competing substrates, even though adaptive substitutions may affect K(M) and k(cat) separately. In total, these results indicate that nonpreferred, or even latent, ancestral protein activities may be coopted at later times to become the primary or preferred protein activities. PMID- 22315397 TI - Dominant eukaryotic export production during ocean anoxic events reflects the importance of recycled NH4+. AB - The Mesozoic is marked by several widespread occurrences of intense organic matter burial. Sediments from the largest of these events, the Cenomanian Turonian Oceanic Anoxic Event (OAE 2) are characterized by lower nitrogen isotope ratios than are seen in modern marine settings. It has remained a challenge to describe a nitrogen cycle that could achieve such isotopic depletion. Here we use nitrogen-isotope ratios of porphyrins to show that eukaryotes contributed the quantitative majority of export production throughout OAE 2, whereas cyanobacteria contributed on average approximately 20%. Such data require that any explanation for the OAE nitrogen cycle and its isotopic values be consistent with a eukaryote-dominated ecosystem. Our results agree with models that suggest the OAEs were high-productivity events, supported by vigorous upwelling. Upwelling of anoxic deep waters would have supplied reduced N species (i.e., NH(4)(+)) to primary producers. We propose that new production during OAE 2 primarily was driven by direct NH(4)(+)-assimilation supplemented by diazotrophy, whereas chemocline denitrification and anammox quantitatively consumed NO(3)(-) and NO(2)(-). A marine nitrogen reservoir dominated by NH(4)(+), in combination with known kinetic isotope effects, could lead to eukaryotic biomass depleted in (15)N. PMID- 22315398 TI - Protein phosphatase 1 subunit Ppp1r15a/GADD34 regulates cytokine production in polyinosinic:polycytidylic acid-stimulated dendritic cells. AB - In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation that exhibits specific mechanisms to control the immune response. Here we show that in response to polyriboinosinic:polyribocytidylic acid (pI:C), DCs mount a specific integrated stress response during which the transcription factor ATF4 and the growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a), a phosphatase 1 (PP1) cofactor, are expressed. In agreement with increased GADD34 levels, an extensive dephosphorylation of the translation initiation factor eIF2alpha was observed during DC activation. Unexpectedly, although DCs display an unusual resistance to protein synthesis inhibition induced in response to cytosolic dsRNA, GADD34 expression did not have a major impact on protein synthesis. GADD34, however, was shown to be required for normal cytokine production both in vitro and in vivo. These observations have important implications in linking further pathogen detection with the integrated stress response pathways. PMID- 22315399 TI - Chimpanzees' flexible targeted helping based on an understanding of conspecifics' goals. AB - Humans extensively help others altruistically, which plays an important role in maintaining cooperative societies. Although some nonhuman animals are also capable of helping others altruistically, humans are considered unique in our voluntary helping and our variety of helping behaviors. Many still believe that this is because only humans can understand others' goals due to our unique "theory of mind" abilities, especially shared intentionality. However, we know little of the cognitive mechanisms underlying helping in nonhuman animals, especially if and how they understand others' goals. The present study provides the empirical evidence for flexible targeted helping depending on conspecifics' needs in chimpanzees. The subjects of this study selected an appropriate tool from a random set of seven objects to transfer to a conspecific partner confronted with differing tool-use situations, indicating that they understood what their partner needed. This targeted helping, (i.e., selecting the appropriate tool to transfer), was observed only when the helpers could visually assess their partner's situation. If visual access was obstructed, the chimpanzees still tried to help their partner upon request, but failed to select and donate the appropriate tool needed by their partner. These results suggest that the limitation in chimpanzees' voluntary helping is not necessarily due to failure in understanding others' goals. Chimpanzees can understand conspecifics' goals and demonstrate cognitively advanced targeted helping as long as they are able to visually evaluate their conspecifics' predicament. However, they will seldom help others without direct request for help. PMID- 22315400 TI - Optimal inference of sameness. AB - Deciding whether a set of objects are the same or different is a cornerstone of perception and cognition. Surprisingly, no principled quantitative model of sameness judgment exists. We tested whether human sameness judgment under sensory noise can be modeled as a form of probabilistically optimal inference. An optimal observer would compare the reliability-weighted variance of the sensory measurements with a set size-dependent criterion. We conducted two experiments, in which we varied set size and individual stimulus reliabilities. We found that the optimal-observer model accurately describes human behavior, outperforms plausible alternatives in a rigorous model comparison, and accounts for three key findings in the animal cognition literature. Our results provide a normative footing for the study of sameness judgment and indicate that the notion of perception as near-optimal inference extends to abstract relations. PMID- 22315401 TI - Federal seafood safety response to the Deepwater Horizon oil spill. AB - Following the 2010 Deepwater Horizon oil spill, petroleum-related compounds and chemical dispersants were detected in the waters of the Gulf of Mexico. As a result, there was concern about the risk to human health through consumption of contaminated seafood in the region. Federal and Gulf Coast State agencies worked together on a sampling plan and analytical protocols to determine whether seafood was safe to eat and acceptable for sale in the marketplace. Sensory and chemical methods were used to measure polycyclic aromatic hydrocarbons (PAHs) and dispersant in >8,000 seafood specimens collected in federal waters of the Gulf. Overall, individual PAHs and the dispersant component dioctyl sodium sulfosuccinate were found in low concentrations or below the limits of quantitation. When detected, the concentrations were at least two orders of magnitude lower than the level of concern for human health risk. Once an area closed to fishing was free of visibly floating oil and all sensory and chemical results for the seafood species within an area met the criteria for reopening, that area was eligible to be reopened. On April 19, 2011 the area around the wellhead was the last area in federal waters to be reopened nearly 1 y after the spill began. However, as of November 9, 2011, some state waters off the Louisiana coast (Barataria Bay and the Delta region) remain closed to fishing. PMID- 22315402 TI - Transcription factor LIM homeobox 7 (Lhx7) maintains subtype identity of cholinergic interneurons in the mammalian striatum. AB - The generation and maintenance of a plethora of neuronal subtypes is essential for normal brain function. Nevertheless, little is known about the molecular mechanisms that maintain the defining characteristics of neurons following their initial postmitotic specification. Using conditional gene ablation in mice, we demonstrate here that the homeodomain protein LIM homeobox (Lhx)7 is essential for maintaining the morphological and molecular characteristics of cholinergic interneurons of the striatum. Lhx7-depleted cholinergic interneurons extinguish expression of several subtype-specific markers, including choline acetyl transferase and Isl1, and are respecified into Lhx6-expressing mature GABAergic interneurons. Additional expression studies support a model where Lhx7 controls the choice between cholinergic or GABAergic identity by gating a cross inhibitory regulation between Isl1 and Lhx6. By demonstrating that the switch between alternative striatal interneuron fates depends on persistent activity of a single transcription factor, we provide evidence that the intrinsic plasticity of mammalian forebrain neuronal subtypes is maintained after the initial specification and lineage commitment and possibly throughout life. PMID- 22315403 TI - Essential requirement for beta-arrestin2 in mouse intestinal tumors with elevated Wnt signaling. AB - beta-Arrestins (Arrb) participate in the regulation of multiple signaling pathways, including Wnt/beta-catenin, the major actor in human colorectal cancer initiation. To better understand the roles of Arrb in intestinal tumorigenesis, a reverse genetic approach (Arrb(-/-)) and in vivo siRNA treatment were used in Apc(Delta14/+) mice. Mice with Arrb2 depletion (knockout and siRNA) developed only 33% of the tumors detected in their Arrb2-WT littermates, whereas Arrb1 depletion remained without significant effect. These remaining tumors grow normally and are essentially Arrb2-independent. Unsupervised hierarchical clustering analysis showed that they clustered with 25% of Apc(Delta14/+);Arrb2(+/+) tumors. Genes overexpressed in this subset reflect a high interaction with the immune system, whereas those overexpressed in Arrb2 dependent tumors are predominantly involved in Wnt signaling, cell adhesion, migration, and extracellular matrix remodeling. The involvement of Arrb2 in intestinal tumor development via the regulation of the Wnt pathway is supported by ex vivo and in vitro experiments using either tumors from Apc(Delta14/+) mice or murine Apc(Min/+) cells. Indeed, Arrb2 siRNAs decreased the expression of Wnt target genes in cells isolated from 12 of 18 tumors from Apc(Delta14/+) mice. In Apc(Min/+) cells, Arrb2 siRNAs completely reversed the increased Wnt activity and colony formation in soft agar induced by Apc siRNA treatment, whereas they did not affect these parameters in basal conditions or in cells expressing constitutively active beta-catenin. We demonstrate that Arrb2 is essential for the initiation and growth of intestinal tumors displaying elevated Wnt pathway activity and identify a previously unsuspected molecular heterogeneity among tumors induced by truncating Apc mutations. PMID- 22315405 TI - Aberration-free three-dimensional multiphoton imaging of neuronal activity at kHz rates. AB - Multiphoton microscopy is a powerful tool in neuroscience, promising to deliver important data on the spatiotemporal activity within individual neurons as well as in networks of neurons. A major limitation of current technologies is the relatively slow scan rates along the z direction compared to the kHz rates obtainable in the x and y directions. Here, we describe a custom-built microscope system based on an architecture that allows kHz scan rates over hundreds of microns in all three dimensions without introducing aberration. We further demonstrate how this high-speed 3D multiphoton imaging system can be used to study neuronal activity at millisecond resolution at the subcellular as well as the population level. PMID- 22315404 TI - Role of retroviral restriction factors in the interferon-alpha-mediated suppression of HIV-1 in vivo. AB - The antiviral potency of the cytokine IFN-alpha has been long appreciated but remains poorly understood. A number of studies have suggested that induction of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 (APOBEC3) and bone marrow stromal cell antigen 2 (BST-2/tetherin/CD317) retroviral restriction factors underlies the IFN-alpha-mediated suppression of HIV-1 replication in vitro. We sought to characterize the as-yet-undefined relationship between IFN alpha treatment, retroviral restriction factors, and HIV-1 in vivo. APOBEC3G, APOBEC3F, and BST-2 expression levels were measured in HIV/hepatitis C virus (HCV)-coinfected, antiretroviral therapy-naive individuals before, during, and after pegylated IFN-alpha/ribavirin (IFN-alpha/riba) combination therapy. IFN alpha/riba therapy decreased HIV-1 viral load by -0.921 (+/-0.858) log(10) copies/mL in HIV/HCV-coinfected patients. APOBEC3G/3F and BST-2 mRNA expression was significantly elevated during IFN-alpha/riba treatment in patient-derived CD4+ T cells (P < 0.04 and P < 0.008, paired Wilcoxon), and extent of BST-2 induction was correlated with reduction in HIV-1 viral load during treatment (P < 0.05, Pearson's r). APOBEC3 induction during treatment was correlated with degree of viral hypermutation (P < 0.03, Spearman's rho), and evolution of the HIV-1 accessory protein viral protein U (Vpu) during IFN-alpha/riba treatment was suggestive of increased BST-2-mediated selection pressure. These data suggest that host restriction factors play a critical role in the antiretroviral capacity of IFN-alpha in vivo, and warrant investigation into therapeutic strategies that specifically enhance the expression of these intrinsic immune factors in HIV-1 infected individuals. PMID- 22315406 TI - Individual variability in functional connectivity predicts performance of a perceptual task. AB - People differ in their ability to perform novel perceptual tasks, both during initial exposure and in the rate of improvement with practice. It is also known that regions of the brain recruited by particular tasks change their activity during learning. Here we investigate neural signals predictive of individual variability in performance. We used resting-state functional MRI to assess functional connectivity before training on a novel visual discrimination task. Subsequent task performance was related to functional connectivity measures within portions of visual cortex and between visual cortex and prefrontal association areas. Our results indicate that individual differences in performing novel perceptual tasks can be related to individual differences in spontaneous cortical activity. PMID- 22315407 TI - Inactivation of androgen-induced regulator ARD1 inhibits androgen receptor acetylation and prostate tumorigenesis. AB - Androgen signaling through androgen receptor (AR) is critical for prostate tumorigenesis. Given that AR-mediated gene regulation is enhanced by AR coregulators, inactivation of those coregulators is emerging as a promising therapy for prostate cancer (PCa). Here, we show that the N-acetyltransferase arrest-defect 1 protein (ARD1) functions as a unique AR regulator in PCa cells. ARD1 is up-regulated in human PCa cell lines and primary tumor biopsies. The expression of ARD1 was augmented by treatment with synthetic androgen (R1881) unless AR is deficient or is inhibited by AR-specific siRNA or androgen inhibitor bicalutamide (Casodex). Depletion of ARD1 by shRNA suppressed PCa cell proliferation, anchorage-independent growth, and xenograft tumor formation in SCID mice, suggesting that AR-dependent ARD1 expression is biologically germane. Notably, ARD1 was critical for transcriptionally regulating a number of AR target genes that are involved in prostate tumorigenesis. Furthermore, ARD1 interacted physically with and acetylated the AR protein in vivo and in vitro. Because AR ARD1 interaction facilitated the AR binding to its targeted promoters for gene transcription, we propose that ARD1 functions as a unique AR regulator and forms a positive feedback loop for AR-dependent prostate tumorigenesis. Disruption of AR-ARD1 interactions may be a potent intervention for androgen-dependent PCa therapy. PMID- 22315408 TI - MicroRNA-132 dysregulation in schizophrenia has implications for both neurodevelopment and adult brain function. AB - Schizophrenia is characterized by affective, cognitive, neuromorphological, and molecular abnormalities that may have a neurodevelopmental origin. MicroRNAs (miRNAs) are small noncoding RNA sequences critical to neurodevelopment and adult neuronal processes by coordinating the activity of multiple genes within biological networks. We examined the expression of 854 miRNAs in prefrontal cortical tissue from 100 control, schizophrenic, and bipolar subjects. The cyclic AMP-responsive element binding- and NMDA-regulated microRNA miR-132 was significantly down-regulated in both the schizophrenic discovery cohort and a second, independent set of schizophrenic subjects. Analysis of miR-132 target gene expression in schizophrenia gene-expression microarrays identified 26 genes up-regulated in schizophrenia subjects. Consistent with NMDA-mediated hypofunction observed in schizophrenic subjects, administration of an NMDA antagonist to adult mice results in miR-132 down-regulation in the prefrontal cortex. Furthermore, miR-132 expression in the murine prefrontal cortex exhibits significant developmental regulation and overlaps with critical neurodevelopmental processes during adolescence. Adult prefrontal expression of miR-132 can be down-regulated by pharmacologic inhibition of NMDA receptor signaling during a brief postnatal period. Several key genes, including DNMT3A, GATA2, and DPYSL3, are regulated by miR-132 and exhibited altered expression either during normal neurodevelopment or in tissue from adult schizophrenic subjects. Our data suggest miR-132 dysregulation and subsequent abnormal expression of miR-132 target genes contribute to the neurodevelopmental and neuromorphological pathologies present in schizophrenia. PMID- 22315409 TI - Cortical topography of intracortical inhibition influences the speed of decision making. AB - The neocortex contains orderly topographic maps; however, their functional role remains controversial. Theoretical studies have suggested a role in minimizing computational costs, whereas empirical studies have focused on spatial localization. Using a tactile multiple-choice reaction time (RT) task before and after the induction of perceptual learning through repetitive sensory stimulation, we extend the framework of cortical topographies by demonstrating that the topographic arrangement of intracortical inhibition contributes to the speed of human perceptual decision-making processes. RTs differ among fingers, displaying an inverted U-shaped function. Simulations using neural fields show the inverted U-shaped RT distribution as an emergent consequence of lateral inhibition. Weakening inhibition through learning shortens RTs, which is modeled through topographically reorganized inhibition. Whereas changes in decision making are often regarded as an outcome of higher cortical areas, our data show that the spatial layout of interaction processes within representational maps contributes to selection and decision-making processes. PMID- 22315410 TI - The heterogeneous motility of the Lyme disease spirochete in gelatin mimics dissemination through tissue. AB - The Lyme disease spirochete Borrelia burgdorferi exists in nature in an enzootic cycle that involves the arthropod vector Ixodes scapularis and mammalian reservoirs. To disseminate within and between these hosts, spirochetes must migrate through complex, polymeric environments such as the basement membrane of the tick midgut and the dermis of the mammal. To date, most research on the motility of B. burgdorferi has been done in media that do not resemble the tissue milieus that B. burgdorferi encounter in vivo. Here we show that the motility of Borrelia in gelatin matrices in vitro resembles the pathogen's movements in the chronically infected mouse dermis imaged by intravital microscopy. More specifically, B. burgdorferi motility in mouse dermis and gelatin is heterogeneous, with the bacteria transitioning between at least three different motility states that depend on transient adhesions to the matrix. We also show that B. burgdorferi is able to penetrate matrices with pore sizes much smaller than the diameter of the bacterium. We find a complex relationship between the swimming behavior of B. burgdorferi and the rheological properties of the gelatin, which cannot be accounted for by recent theoretical predictions for microorganism swimming in gels. Our results also emphasize the importance of considering borrelial adhesion as a dynamic rather than a static process. PMID- 22315411 TI - Charged linker sequence modulates eukaryotic heat shock protein 90 (Hsp90) chaperone activity. AB - Hsp90 is an essential and highly conserved modular molecular chaperone whose N and middle domains are separated by a disordered region termed the charged linker. Although its importance has been previously disregarded, because a minimal linker length is sufficient for Hsp90 activity, the evolutionary persistence of extensive charged linkers of divergent sequence in Hsp90 proteins of most eukaryotes remains unexplained. To examine this question further, we introduced human and plasmodium native and length-matched artificial linkers into yeast Hsp90. After evaluating ATPase activity and biophysical characteristics in vitro, and chaperone function in vivo, we conclude that linker sequence affects Hsp90 function, cochaperone interaction, and conformation. We propose that the charged linker, in addition to providing the flexibility necessary for Hsp90 domain rearrangements--likely its original purpose--has evolved in eukaryotes to serve as a rheostat for the Hsp90 chaperone machine. PMID- 22315412 TI - The protein kinase Akt1 regulates the interferon response through phosphorylation of the transcriptional repressor EMSY. AB - The protein kinases Akt1, Akt2, and Akt3 possess nonredundant signaling properties, few of which have been investigated. Here, we present evidence for an Akt1-dependent pathway that controls interferon (IFN)-regulated gene expression and antiviral immunity. The target of this pathway is EMSY, an oncogenic interacting partner of BRCA2 that functions as a transcriptional repressor. Overexpression of EMSY in hTERT-immortalized mammary epithelial cells, and in breast and ovarian carcinoma cell lines, represses IFN-stimulated genes (ISGs) in a BRCA2-dependent manner, whereas its knockdown has the opposite effect. EMSY binds to the promoters of ISGs, suggesting that EMSY functions as a direct transcriptional repressor. Akt1, but not Akt2, phosphorylates EMSY at Ser209, relieving EMSY-mediated ISG repression. The Akt1/EMSY/ISG pathway is activated by both viral infection and IFN, and it inhibits the replication of HSV-1 and vesicular stomatitis virus (VSV). Collectively, these data define an Akt1 dependent pathway that contributes to the full activation of ISGs by relieving their repression by EMSY and BRCA2. PMID- 22315413 TI - Sweet taste receptor signaling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion. AB - Postprandial insulin release is regulated by glucose, but other circulating nutrients may target beta cells and potentiate glucose-stimulated insulin secretion via distinct signaling pathways. We demonstrate that fructose activates sweet taste receptors (TRs) on beta cells and synergizes with glucose to amplify insulin release in human and mouse islets. Genetic ablation of the sweet TR protein T1R2 obliterates fructose-induced insulin release and its potentiating effects on glucose-stimulated insulin secretion in vitro and in vivo. TR signaling in beta cells is triggered, at least in part, in parallel with the glucose metabolic pathway and leads to increases in intracellular calcium that are dependent on the activation of phospholipase C (PLC) and transient receptor potential cation channel, subfamily M, member 5 (TRPM5). Our results unveil a pathway for the regulation of insulin release by postprandial nutrients that involves beta cell sweet TR signaling. PMID- 22315414 TI - The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule. AB - IRE1 couples endoplasmic reticulum unfolded protein load to RNA cleavage events that culminate in the sequence-specific splicing of the Xbp1 mRNA and in the regulated degradation of diverse membrane-bound mRNAs. We report on the identification of a small molecule inhibitor that attains its selectivity by forming an unusually stable Schiff base with lysine 907 in the IRE1 endonuclease domain, explained by solvent inaccessibility of the imine bond in the enzyme inhibitor complex. The inhibitor (abbreviated 4MU8C) blocks substrate access to the active site of IRE1 and selectively inactivates both Xbp1 splicing and IRE1 mediated mRNA degradation. Surprisingly, inhibition of IRE1 endonuclease activity does not sensitize cells to the consequences of acute endoplasmic reticulum stress, but rather interferes with the expansion of secretory capacity. Thus, the chemical reactivity and sterics of a unique residue in the endonuclease active site of IRE1 can be exploited by selective inhibitors to interfere with protein secretion in pathological settings. PMID- 22315415 TI - Plasmacytoid dendritic cells control T-cell response to chronic viral infection. AB - Infections with persistent viruses are a frequent cause of immunosuppression, autoimmune sequelae, and/or neoplastic disease. Plasmacytoid dendritic cells (pDCs) are innate immune cells that produce type I interferon (IFN-I) and other cytokines in response to virus-derived nucleic acids. Persistent viruses often cause depletion or functional impairment of pDCs, but the role of pDCs in the control of these viruses remains unclear. We used conditional targeting of pDC specific transcription factor E2-2 to generate mice that constitutively lack pDCs in peripheral lymphoid organs and tissues. The profound impact of pDC deficiency on innate antiviral responses was revealed by the failure to control acute infection with the cytopathic mouse hepatitis virus. Furthermore, pDC-deficient animals failed to clear lymphocytic choriomeningitis virus (LCMV) from hematopoietic organs during persistent LCMV infection. This failure was associated with reduced numbers and functionality of LCMV-specific CD4(+) helper T cells and impaired antiviral CD8(+) T-cell responses. Adoptive transfer of LCMV specific T cells revealed that both CD4(+) and CD8(+) T cells required IFN-I for expansion, but only CD4(+) T cells required the presence of pDCs. In contrast, mice with pDC-specific loss of MHC class II expression supported normal CD4(+) T cell response to LCMV. These data suggest that pDCs facilitate CD4(+) helper T cell responses to persistent viruses independently of direct antigen presentation. Thus pDCs provide an essential link between innate and adaptive immunity to chronic viral infection, likely through the secretion of IFN-I and other cytokines. PMID- 22315416 TI - Wing stridulation in a Jurassic katydid (Insecta, Orthoptera) produced low pitched musical calls to attract females. AB - Behaviors are challenging to reconstruct for extinct species, particularly the nature and origins of acoustic communication. Here we unravel the song of Archaboilus musicus Gu, Engel and Ren sp. nov., a 165 million year old stridulating katydid. From the exceptionally preserved morphology of its stridulatory apparatus in the forewings and phylogenetic comparison with extant species, we reveal that A. musicus radiated pure-tone (musical) songs using a resonant mechanism tuned at a frequency of 6.4 kHz. Contrary to previous scenarios, musical songs were an early innovation, preceding the broad-bandwidth songs of extant katydids. Providing an accurate insight into paleoacoustic ecology, the low-frequency musical song of A. musicus was well-adapted to communication in the lightly cluttered environment of the mid-Jurassic forest produced by coniferous trees and giant ferns, suggesting that reptilian, amphibian, and mammalian insectivores could have also heard A. musicus' song. PMID- 22315417 TI - Transient Ru-methyl formate intermediates generated with bifunctional transfer hydrogenation catalysts. AB - Desorption electrospray ionization (DESI) coupled to high-resolution Orbitrap mass spectrometry (MS) was used to study the reactivity of a (beta-amino alcohol)(arene)RuCl transfer hydrogenation catalytic precursor in methanol (CH(3)OH). By placing [(p-cymene)RuCl(2)](2) on a surface and spraying a solution of beta-amino alcohol in methanol, two unique transient intermediates having lifetimes in the submillisecond to millisecond range were detected. These intermediates were identified as Ru (II) and Ru (IV) complexes incorporating methyl formate (HCOOCH(3)). The Ru (IV) intermediate is not observed when the DESI spray solution is sparged with Ar gas, indicating that O(2) dissolved in the solvent is necessary for oxidizing Ru (II) to Ru (IV). These proposed intermediates are supported by high-resolution and high mass accuracy measurements and by comparing experimental to calculated isotope profiles. Additionally, analyzing the bulk reaction mixture using gas chromatography-MS and nuclear magnetic resonance spectroscopy confirms the formation of HCOOCH(3). These results represent an example that species generated from the (beta-amino alcohol)(arene)RuCl (II) catalytic precursor can selectively oxidize CH(3)OH to HCOOCH(3). This observation leads us to propose a pathway that can compete with the hydrogen transfer catalytic cycle. Although bifunctional hydrogen transfer with Ru catalysts has been well-studied, the ability of DESI to intercept intermediates formed in the first few milliseconds of a chemical reaction allowed identification of previously unrecognized intermediates and reaction pathways in this catalytic system. PMID- 22315418 TI - On relaxations and aging of various glasses. AB - Slow relaxation occurs in many physical and biological systems. "Creep" is an example from everyday life. When stretching a rubber band, for example, the recovery to its equilibrium length is not, as one might think, exponential: The relaxation is slow, in many cases logarithmic, and can still be observed after many hours. The form of the relaxation also depends on the duration of the stretching, the "waiting time." This ubiquitous phenomenon is called aging, and is abundant both in natural and technological applications. Here, we suggest a general mechanism for slow relaxations and aging, which predicts logarithmic relaxations, and a particular aging dependence on the waiting time. We demonstrate the generality of the approach by comparing our predictions to experimental data on a diverse range of physical phenomena, from conductance in granular metals to disordered insulators and dirty semiconductors, to the low temperature dielectric properties of glasses. PMID- 22315419 TI - Insights from past millennia into climatic impacts on human health and survival. AB - Climate change poses threats to human health, safety, and survival via weather extremes and climatic impacts on food yields, fresh water, infectious diseases, conflict, and displacement. Paradoxically, these risks to health are neither widely nor fully recognized. Historical experiences of diverse societies experiencing climatic changes, spanning multicentury to single-year duration, provide insights into population health vulnerability--even though most climatic changes were considerably less than those anticipated this century and beyond. Historical experience indicates the following. (i) Long-term climate changes have often destabilized civilizations, typically via food shortages, consequent hunger, disease, and unrest. (ii) Medium-term climatic adversity has frequently caused similar health, social, and sometimes political consequences. (iii) Infectious disease epidemics have often occurred in association with briefer episodes of temperature shifts, food shortages, impoverishment, and social disruption. (iv) Societies have often learnt to cope (despite hardship for some groups) with recurring shorter-term (decadal to multiyear) regional climatic cycles (e.g., El Nino Southern Oscillation)--except when extreme phases occur. (v) The drought-famine-starvation nexus has been the main, recurring, serious threat to health. Warming this century is not only likely to greatly exceed the Holocene's natural multidecadal temperature fluctuations but to occur faster. Along with greater climatic variability, models project an increased geographic range and severity of droughts. Modern societies, although larger, better resourced, and more interconnected than past societies, are less flexible, more infrastructure-dependent, densely populated, and hence are vulnerable. Adverse historical climate-related health experiences underscore the case for abating human-induced climate change. PMID- 22315420 TI - Human genetic variation altering anthrax toxin sensitivity. AB - The outcome of exposure to infectious microbes or their toxins is influenced by both microbial and host genes. Some host genes encode defense mechanisms, whereas others assist pathogen functions. Genomic analyses have associated host gene mutations with altered infectious disease susceptibility, but evidence for causality is limited. Here we demonstrate that human genetic variation affecting capillary morphogenesis gene 2 (CMG2), which encodes a host membrane protein exploited by anthrax toxin as a principal receptor, dramatically alters toxin sensitivity. Lymphoblastoid cells derived from a HapMap Project cohort of 234 persons of African, European, or Asian ancestry differed in sensitivity mediated by the protective antigen (PA) moiety of anthrax toxin by more than four orders of magnitude, with 99% of the cohort showing a 250-fold range of sensitivity. We find that relative sensitivity is an inherited trait that correlates strongly with CMG2 mRNA abundance in cells of each ethnic/geographical group and in the combined population pool (P = 4 * 10(-11)). The extent of CMG2 expression in transfected murine macrophages and human lymphoblastoid cells affected anthrax toxin binding, internalization, and sensitivity. A CMG2 single-nucleotide polymorphism (SNP) occurring frequently in African and European populations independently altered toxin uptake, but was not statistically associated with altered sensitivity in HapMap cell populations. Our results reveal extensive human diversity in cell lethality dependent on PA-mediated toxin binding and uptake, and identify individual differences in CMG2 expression level as a determinant of this diversity. Testing of genomically characterized human cell populations may offer a broadly useful strategy for elucidating effects of genetic variation on infectious disease susceptibility. PMID- 22315421 TI - Genomic epidemiology of the Escherichia coli O104:H4 outbreaks in Europe, 2011. AB - The degree to which molecular epidemiology reveals information about the sources and transmission patterns of an outbreak depends on the resolution of the technology used and the samples studied. Isolates of Escherichia coli O104:H4 from the outbreak centered in Germany in May-July 2011, and the much smaller outbreak in southwest France in June 2011, were indistinguishable by standard tests. We report a molecular epidemiological analysis using multiplatform whole genome sequencing and analysis of multiple isolates from the German and French outbreaks. Isolates from the German outbreak showed remarkably little diversity, with only two single nucleotide polymorphisms (SNPs) found in isolates from four individuals. Surprisingly, we found much greater diversity (19 SNPs) in isolates from seven individuals infected in the French outbreak. The German isolates form a clade within the more diverse French outbreak strains. Moreover, five isolates derived from a single infected individual from the French outbreak had extremely limited diversity. The striking difference in diversity between the German and French outbreak samples is consistent with several hypotheses, including a bottleneck that purged diversity in the German isolates, variation in mutation rates in the two E. coli outbreak populations, or uneven distribution of diversity in the seed populations that led to each outbreak. PMID- 22315422 TI - IL-38 binds to the IL-36 receptor and has biological effects on immune cells similar to IL-36 receptor antagonist. AB - The functional role of IL-1 family member 10, recently renamed IL-38, remains unknown. In the present study we aimed to elucidate the biological function of IL 38 and to identify its receptor. Heat-killed Candida albicans was used to stimulate memory T-lymphocyte cytokine production in freshly obtained human peripheral blood mononuclear cells from healthy subjects. The addition of recombinant IL-38 (152 amino acids) inhibited the production of T-cell cytokines IL-22 (37% decrease) and IL-17 (39% decrease). The reduction in IL-22 and IL-17 caused by IL-38 was similar to that caused by the naturally occurring IL-36 receptor antagonist (IL-36Ra) in the same peripheral blood mononuclear cells cultures. IL-8 production induced by IL-36gamma was reduced by IL-38 (42% decrease) and also was reduced by IL-36Ra (73% decrease). When human blood monocyte-derived dendritic cells were used, IL-38 as well as IL-36Ra increased LPS-induced IL-6 by twofold. We screened immobilized extracellular domains of each member of the IL-1 receptor family, including the IL-36 receptor (also known as "IL-1 receptor-related protein 2") and observed that IL-38 bound only to the IL-36 receptor, as did IL-36Ra. The dose-response suppression of IL-38 as well as that of IL-36Ra of Candida-induced IL-22 and IL-17 was not that of the classic IL 1 receptor antagonist (anakinra), because low concentrations were optimal for inhibiting IL-22 production, whereas higher concentrations modestly increased IL 22. These data provide evidence that IL-38 binds to the IL-36R, as does IL-36Ra, and that IL-38 and IL-36Ra have similar biological effects on immune cells by engaging the IL-36 receptor. PMID- 22315423 TI - Congenital diaphragmatic hernia candidate genes derived from embryonic transcriptomes. AB - Congenital diaphragmatic hernia (CDH) is a common (1 in 3,000 live births) major congenital malformation that results in significant morbidity and mortality. The discovery of CDH loci using standard genetic approaches has been hindered by its genetic heterogeneity. We hypothesized that gene expression profiling of developing embryonic diaphragms would help identify genes likely to be associated with diaphragm defects. We generated a time series of whole-transcriptome expression profiles from laser captured embryonic mouse diaphragms at embryonic day (E)11.5 and E12.5 when experimental perturbations lead to CDH phenotypes, and E16.5 when the diaphragm is fully formed. Gene sets defining biologically relevant pathways and temporal expression trends were identified by using a series of bioinformatic algorithms. These developmental sets were then compared with a manually curated list of genes previously shown to cause diaphragm defects in humans and in mouse models. Our integrative filtering strategy identified 27 candidates for CDH. We examined the diaphragms of knockout mice for one of the candidate genes, pre-B-cell leukemia transcription factor 1 (Pbx1), and identified a range of previously undetected diaphragmatic defects. Our study demonstrates the utility of genetic characterization of normal development as an integral part of a disease gene identification and prioritization strategy for CDH, an approach that can be extended to other diseases and developmental anomalies. PMID- 22315424 TI - Breast cancer signatures for invasiveness and prognosis defined by deep sequencing of microRNA. AB - The transition from ductal carcinoma in situ to invasive ductal carcinoma is a key event in breast cancer progression that is still not well understood. To discover the microRNAs regulating this critical transition, we used 80 biopsies from invasive ductal carcinoma, 8 from ductal carcinoma in situ, and 6 from normal breast. We selected them from a recently published deep-sequencing dataset [Farazi TA, et al. (2011) Cancer Res 71:4443-4453]. The microRNA profile established for the normal breast to ductal carcinoma in situ transition was largely maintained in the in situ to invasive ductal carcinoma transition. Nevertheless, a nine-microRNA signature was identified that differentiated invasive from in situ carcinoma. Specifically, let-7d, miR-210, and -221 were down-regulated in the in situ and up-regulated in the invasive transition, thus featuring an expression reversal along the cancer progression path. Additionally, we identified microRNAs for overall survival and time to metastasis. Five noncoding genes were associated with both prognostic signatures--miR-210, -21, 106b*, -197, and let-7i, with miR-210 the only one also involved in the invasive transition. To pinpoint critical cellular functions affected in the invasive transition, we identified the protein coding genes with inversely related profiles to miR-210: BRCA1, FANCD, FANCF, PARP1, E-cadherin, and Rb1 were all activated in the in situ and down-regulated in the invasive carcinoma. Additionally, we detected differential splicing isoforms with special features, including a truncated EGFR lacking the kinase domain and overexpressed only in ductal carcinoma in situ. PMID- 22315425 TI - Arabidopsis circadian clock protein, TOC1, is a DNA-binding transcription factor. AB - The first described feedback loop of the Arabidopsis circadian clock is based on reciprocal regulation between Timing of CAB Expression 1 (TOC1) and Circadian Clock-associated 1 (CCA1)/late elongated hypocotyl (LHY). CCA1 and LHY are Myb transcription factors that bind directly to the TOC1 promoter to negatively regulate its expression. Conversely, the activity of TOC1 has remained less well characterized. Genetic data support that TOC1 is necessary for the reactivation of CCA1/LHY, but there is little description of its biochemical function. Here we show that TOC1 occupies specific genomic regions in the CCA1 and LHY promoters. Purified TOC1 binds directly to DNA through its CCT domain, which is similar to known DNA-binding domains. Chemical induction and transient overexpression of TOC1 in Arabidopsis seedlings cause repression of CCA1/LHY expression, demonstrating that TOC1 can repress direct targets, and mutation or deletion of the CCT domain prevents this repression showing that DNA-binding is necessary for TOC1 action. Furthermore, we use the Gal4/UAS system in Arabidopsis to show that TOC1 acts as a general transcriptional repressor, and that repression activity is in the pseudoreceiver domain of the protein. To identify the genes regulated by TOC1 on a genomic scale, we couple TOC1 chemical induction with microarray analysis and identify previously unexplored potential TOC1 targets and output pathways. Taken together, these results define a biochemical action for the core clock protein TOC1 and refine our perspective on how plant clocks function. PMID- 22315426 TI - Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 protein. AB - Mammalian cells are capable of delivering multiple types of membrane capsules extracellularly. The limiting membrane of late endosomes can fuse with the plasma membrane, leading to the extracellular release of multivesicular bodies (MVBs), initially contained within the endosomes, as exosomes. Budding viruses exploit the TSG101 protein and endosomal sorting complex required for transport (ESCRT) machinery used for MVB formation to mediate the egress of viral particles from host cells. Here we report the discovery of a virus-independent cellular process that generates microvesicles that are distinct from exosomes and which, like budding viruses, are produced by direct plasma membrane budding. Such budding is driven by a specific interaction of TSG101 with a tetrapeptide PSAP motif of an accessory protein, arrestin domain-containing protein 1 (ARRDC1), which we show is localized to the plasma membrane through its arrestin domain. This interaction results in relocation of TSG101 from endosomes to the plasma membrane and mediates the release of microvesicles that contain TSG101, ARRDC1, and other cellular proteins. Unlike exosomes, which are derived from MVBs, ARRDC1-mediated microvesicles (ARMMs) lack known late endosomal markers. ARMMs formation requires VPS4 ATPase and is enhanced by the E3 ligase WWP2, which interacts with and ubiquitinates ARRDC1. ARRDC1 protein discharged into ARMMs was observed in co cultured cells, suggesting a role for ARMMs in intercellular communication. Our findings reveal an intrinsic cellular mechanism that results in direct budding of microvesicles from the plasma membrane, providing a formal paradigm for the evolutionary recruitment of ESCRT proteins in the release of budding viruses. PMID- 22315427 TI - Human kinome profiling identifies a requirement for AMP-activated protein kinase during human cytomegalovirus infection. AB - Human cytomegalovirus (HCMV) modulates numerous cellular signaling pathways. Alterations in signaling are evident from the broad changes in cellular phosphorylation that occur during HCMV infection and from the altered activity of multiple kinases. Here we report a comprehensive RNAi screen, which predicts that 106 cellular kinases influence growth of the virus, most of which were not previously linked to HCMV replication. Multiple elements of the AMP-activated protein kinase (AMPK) pathway scored in the screen. As a regulator of carbon and nucleotide metabolism, AMPK is poised to activate many of the metabolic pathways induced by HCMV infection. An AMPK inhibitor, compound C, blocked a substantial portion of HCMV-induced metabolic changes, inhibited the accumulation of all HCMV proteins tested, and markedly reduced the production of infectious progeny. We propose that HCMV requires AMPK or related activity for viral replication and reprogramming of cellular metabolism. PMID- 22315428 TI - Impaired neurotransmission caused by overexpression of alpha-synuclein in nigral dopamine neurons. AB - We used in vivo amperometry to monitor changes in synaptic dopamine (DA) release in the striatum induced by overexpression of human wild-type alpha-synuclein in nigral DA neurons, induced by injection of an adeno-associated virus type 6 (AAV6)-alpha-synuclein vector unilaterally into the substantia nigra in adult rats. Impairments in DA release evolved in parallel with the development of degenerative changes in the nigrostriatal axons and terminals. The earliest change, seen 10 d after vector injection, was a marked, ~50%, reduction in DA reuptake, consistent with an early dysfunction of the DA transporter that developed before any overt signs of axonal damage. At 3 wk, when the first signs of axonal damage were observed, the amount of DA released after a KCl pulse was reduced by 70-80%, and peak DA concentration was delayed, indicating an impaired release mechanism. At later time points, 8-16 wk, overall striatal innervation density was reduced by 60-80% and accompanied by abundant signs of axonal damage in the form of alpha-synuclein aggregates, axonal swellings, and dystrophic axonal profiles. At this stage DA release and reuptake were profoundly reduced, by 80-90%. The early changes in synaptic DA release induced by overexpression of human alpha-synuclein support the idea that early predegenerative changes in the handling of DA may initiate, and drive, a progressive degenerative process that hits the axons and terminals first. Synaptic dysfunction and axonopathy would thus be the hallmark of presymptomatic and early-stage Parkinson disease, followed by neuronal degeneration and cell loss, characteristic of more advanced stages of the disease. PMID- 22315429 TI - Profile of Ken A. Dill. PMID- 22315430 TI - Polycation-siRNA nanoparticles can disassemble at the kidney glomerular basement membrane. AB - Despite being engineered to avoid renal clearance, many cationic polymer (polycation)-based siRNA nanoparticles that are used for systemic delivery are rapidly eliminated from the circulation. Here, we show that a component of the renal filtration barrier--the glomerular basement membrane (GBM)--can disassemble cationic cyclodextrin-containing polymer (CDP)-based siRNA nanoparticles and, thereby, facilitate their rapid elimination from circulation. Using confocal and electron microscopies, positron emission tomography, and compartment modeling, we demonstrate that siRNA nanoparticles, but not free siRNA, accumulate and disassemble in the GBM. We also confirm that the siRNA nanoparticles do not disassemble in blood plasma in vitro and in vivo. This clearance mechanism may affect any nanoparticles that assemble primarily by electrostatic interactions between cationic delivery components and anionic nucleic acids (or other therapeutic entities). PMID- 22315431 TI - Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor gamma. AB - The endocrine hormone fibroblast growth factor 21 (FGF21) is a powerful modulator of glucose and lipid metabolism and a promising drug for type 2 diabetes. Here we identify FGF21 as a potent regulator of skeletal homeostasis. Both genetic and pharmacologic FGF21 gain of function lead to a striking decrease in bone mass. In contrast, FGF21 loss of function leads to a reciprocal high-bone-mass phenotype. Mechanistically, FGF21 inhibits osteoblastogenesis and stimulates adipogenesis from bone marrow mesenchymal stem cells by potentiating the activity of peroxisome proliferator-activated receptor gamma (PPAR-gamma). Consequently, FGF21 deletion prevents the deleterious bone loss side effect of the PPAR-gamma agonist rosiglitazone. Therefore, FGF21 is a critical rheostat for bone turnover and a key integrator of bone and energy metabolism. These results reveal that skeletal fragility may be an undesirable consequence of chronic FGF21 administration. PMID- 22315434 TI - Codeine-induced pulmonary oedema (an unusual cause of dyspnoea). PMID- 22315435 TI - Mutations in NLRP7 are associated with diploid biparental hydatidiform moles, but not androgenetic complete moles. AB - BACKGROUND: NLRP7 (NALP7) has been identified as the major gene involved in the inherited predisposition to recurrent molar pregnancies, a rare recessive condition in which affected individuals have complete hydatidiform moles of diploid biparental origin (BiCHM). The role of NLRP7 in other types of molar pregnancy and reproductive wastage has not been conclusively demonstrated. The purpose of this study was to clarify this by identifying NLRP7 variation in two clinically well-defined groups of patients: women with recurrent BiCHM, and women with three or more recurrent complete hydatidiform moles of proven androgenetic origin (AnCHM). METHODS: Fluorescent microsatellite genotyping of molar tissue was used to establish a diagnosis of recurrent BiCHM (four novel cases) or recurrent AnCHM (nine women with multiple CHM). These two groups were subsequently screened for mutations in NLRP7 using DNA sequencing. Additional screening for non-pathological variants was performed in 21 previously published cases of recurrent BiCHM. Taqman genotyping was used to determine the frequency of novel NLRP7 variants in two control cohorts of Caucasian and Asian women with no adverse reproductive outcomes. RESULTS: Of the four novel cases with recurrent BiCHM, two were homozygous for mutations in NLRP7 while one was a compound heterozygote for a nonsense mutation and a pathological variant. No NLRP7 mutations or pathological variants were identified in the fourth case. None of the women with AnCHM carried any mutations or pathological variants of NLRP7. A single case of AnCHM was found to be heterozygous for a novel variant (R413Q). CONCLUSION: NLRP7 mutations do not represent a major cause of AnCHM. PMID- 22315436 TI - Fabry International Prognostic Index: a predictive severity score for Anderson Fabry disease. AB - BACKGROUND: Anderson-Fabry disease (AFD) is a disorder of glycosphingolipid metabolism resulting from deficiency of alpha-galactosidase A and accumulation of globotriaosylceramide. Presentation is heterogeneous and, despite guidelines for initiation of therapy, there is no basis for defining subgroups that will progress more rapidly, whether treated or not. The authors of this study used clinical and pathological data recorded on 1483 patients in the Fabry Outcome Survey, a large international registry, to develop a prognostic severity score. METHODS: Parameters relevant to disease progression or outcome were initially selected, using variables that are readily available in clinical practice. Individual end points for renal, cardiac, neurological disease, and death were selected, and a composite end point developed. Potential prognostic variables were correlated with each end point, before multivariate analysis. Variables retaining significance were then used to construct organ specific and composite prognostic scores. Kaplan-Meier (KM) analysis, according to score, was performed for each end point. RESULTS: Analysis demonstrated that it is possible to differentiate groups of patients with different outcome probabilities. Cardiac, renal and neurological end points could each be categorised into three separate groups. The 80% event-free survival for these groups differed by approximately 10 years. The overall composite score, the Fabry International Prognostic Index (FIPI), distinguished two distinct groups where the 50% event-free survival differed by 10 years. CONCLUSIONS: A prognostic scoring system for AFD has been developed and retrospective validation performed. The FIPI should prove to be a valuable tool in the counselling and management of AFD patients, and in comparative analyses of outcome using different therapies. PMID- 22315437 TI - Promoter methylation in coagulation F7 gene influences plasma FVII concentrations and relates to coronary artery disease. AB - BACKGROUND: Plasma factor VII concentrations (FVIIa), a marker of coronary artery disease (CAD) risk, are influenced by genetic markers at the promoter site: the A2 allele, due to a 10bp insertion at position -323, is a determinant of lower FVIIa concentrations and reduced CAD risk, while the -402A allele, due to a G>A substitution, confers increased transcriptional activity in vitro resulting in higher FVIIa. Transcriptional regulation of F7 by epigenetic features is, however, still unknown as is the inter-relationship of genetic and epigenetic modifications at the promoter site. OBJECTIVE: To investigate a possible epigenetic regulation of the F7 gene at the promoter region and its link with functional F7 polymorphisms at the same site. METHODS AND RESULTS: F7 promoter methylation and its relation to F7 promoter polymorphisms in modulating FVIIa and CAD risk were evaluated by methyl-specific PCR and bisulfite sequencing techniques in 253 subjects, of whom 168 had CAD and 88 were CAD-free. Plasma FVIIa was inversely related to methylation in A1A1 and -402GG, that is in the absence of the rare A2 and -402A allele. The higher FVIIa paralleled the lower methylation in A1A1 compared to A2A2 (p=0.035), while no variation in methylation was associated with the different -402G>A genotypes. The modulation of methylation-induced FVIIa concentrations was observed only in A1A1 where the higher methylation resulting in lower FVIIa was prevalent within the CAD-free group compared to the CAD group (p=0.011). CONCLUSIONS: Epigenetic regulation through methylation of F7 promoter is associated with CAD by affecting plasma FVIIa concentrations in A1A1 genotypes. PMID- 22315438 TI - Stability evaluation of (18)F-FDG at high radioactive concentrations. AB - The objective of our study was to determine the concentration of ethanol, a known radiolytic stabilizer, needed to maintain stability for 12 h at an (18)F-FDG concentration of 19.7-22.6 GBq/mL (533-610 mCi/mL) at the end of synthesis (EOS). METHODS: (18)F(-) was formed by the (18)O(p, n)(18)F reaction using 16.5-MeV protons on a cyclotron. (18)F-FDG was synthesized using a synthesis platform. The final product was formulated in 15 mL of phosphate buffer. The synthesis took 22 min, delivering up to 336.7 GBq (9.1 Ci) of (18)F-FDG at the EOS. A series of 9 runs, 19.7-22.6 GBq/mL (533-610 mCi/mL), was completed. Three runs were doped with 0.1% ethanol, 3 with 0.2% ethanol, and 3 with no ethanol added. The radiochemical purity (RCP) was tested at about 1-h increments over a 12-h period. RCP was found by radio-thin-layer chromatography using aluminum-backed silica gel plates, acetonitrile, and water 90:10. An (18)F-FDG standard of 1 mg/mL was used to confirm radiochemical identity. The chromatography plates were analyzed on a radio-thin-layer chromatograph using a beta-detector. Residual solvents were also tested using gas chromatography with flame ionization detection and a capillary column. Other quality control measurements performed were pH and appearance. RESULTS: The 3 runs doped with 0.1% ethanol failed RCP after 5 h. The 3 runs using an ethanol concentration of 0.2% maintained stability through 12 h beyond the EOS. For these 3 runs, the radiolytic impurities were relatively constant at 6.1% +/- 0.7% after 3 h. The runs using no ethanol failed RCP at 1 h. The pH varied between 5.3 and 6.1. Visual inspection was always clear and particulate free. For the runs with 0.2% and 0.1% ethanol, the residual solvents were 0.21% +/- 0.02% and 0.10% +/- 0.02%, respectively. Regardless of ethanol concentration, chemical purity and identity passed quality control measurements. CONCLUSION: With the addition of 0.2% ethanol, (18)F-FDG (19.7-22.6 GBq/mL [533-610 mCi/mL]) kept stability through 12 h beyond the EOS. Each run passed stability parameters related to radiolysis-that is, radiochemical identity and RCP, chemical purity and identity, appearance, pH, and residual solvents. PMID- 22315439 TI - Evaluation of 4'-[methyl-11C]thiothymidine in a rodent tumor and inflammation model. AB - 4'-[methyl-(11)C]thiothymidine ((11)C-4DST) is a novel radiopharmaceutical that can be used for tumor imaging because of its rapid incorporation into DNA as a substrate for DNA synthesis. The in vivo stability of (11)C-4DST is much greater than that of natural thymidine, because of the presence of a sulfur atom in the 4'-position. Here, we evaluated the tissue kinetics and biodistribution of (11)C 4DST in a rodent tumor and acute sterile inflammation model in comparison with the previously published biodistribution data of 3'-deoxy-3'-(18)F fluorothymidine ((18)F-FLT), (18)F-FDG, (11)C-choline, (11)C-methionine, and 2 sigma-receptor ligands in the same animal model. METHODS: C6 tumor cells were implanted subcutaneously into the right shoulder and turpentine (0.1 mL) was injected intramuscularly into the left hind leg of male Wistar rats 11 d and 24 h, respectively, before the scanning day. The animals were anesthetized with isoflurane, and (11)C-4DST (20-50 MBq) was injected intravenously. A dynamic PET scan was performed for 60 min with either the shoulder or hind leg region in the field of view. The animals were sacrificed, and a biodistribution study was performed. RESULTS: (11)C-4DST showed the highest tumor uptake (standardized uptake value, 4.93) of all radiopharmaceuticals tested. Its tumor-to-muscle concentration ratio (12.7) was similar to that of (18)F-FDG (13.2). The selectivity of (11)C-4DST for tumor as compared with acute inflammation was high (37.7), comparable to that of the sigma-ligand (18)F-FE-SA5845 and much higher than that of (18)F-FDG (3.5). Rapidly proliferating tissues (tumor and bone marrow) showed a steadily increasing uptake. In inflamed muscle, (11)C-4DST showed relatively rapid washout, and tracer concentrations in inflamed and noninflamed muscle were not significantly different at intervals greater than 40 min. Competition of endogenous thymidine for (11)C-4DST uptake in target tissues was negligible, in contrast to competition for (18)F-FLT uptake. Thus, pretreatment of animals with thymidine phosphorylase was not required before PET with (11)C-4DST. CONCLUSION: In our rodent model, (11)C-4DST showed high tumor uptake (sensitivity) and high tumor selectivity. The different kinetics of (11)C 4DST in rapidly proliferating and inflammatory tissue may allow distinction between tumor and acute inflammation in a clinical setting. These promising results for (11)C-4DST warrant further investigation in PET studies in patients with various types of tumors. PMID- 22315440 TI - PET/CT assessment of symptomatic individuals with obstructive and nonobstructive hypertrophic cardiomyopathy. AB - Patients with obstructive hypertrophic cardiomyopathy (HCM) exhibit elevated left ventricular outflow tract gradients (LVOTGs) and appear to have a worse prognosis than those with nonobstructive HCM. The aim of this study was to evaluate whether patients with obstruction, compared with nonobstructive HCM, demonstrate significant differences in PET parameters of microvascular function. METHODS: PET was performed in 33 symptomatic HCM patients at rest and during dipyridamole stress (peak) for the assessment of regional myocardial perfusion (rMP), left ventricular ejection fraction (LVEF), myocardial blood flow (MBF), and myocardial flow reserve (MFR). Myocardial wall thickness and LVOTG were measured with an echocardiogram. Patients were divided into the following 3 groups: nonobstructive (LVOTG < 30 mm Hg at rest and after provocation test with amyl nitrite), obstructive (LVOTG >= 30 mm Hg at rest and with provocation), and latent HCM (LVOTG < 30 at rest but >= 30 mm Hg with provocation). RESULTS: Eleven patients were classified as nonobstructive (group 1), 12 as obstructive (group 2), and 10 as latent HCM (group 3). Except for age (42 +/- 18 y for group 1, 58 +/- 7 y for group 2, and 58 +/- 12 y for group 3; P = 0.01), all 3 groups had similar baseline characteristics, including maximal wall thickness (2.3 +/- 0.5 cm for group 1, 2.2 +/- 0.4 cm for group 2, and 2.1 +/- 0.7 cm for group 3; P = 0.7). During peak flow, most patients in groups 1 and 2, but fewer in group 3, exhibited rMP defects (73% for group 1, 100% for group 2, and 40% for group 3; P = 0.007) and a drop in LVEF (73% for group 1, 92% for group 2, and 50% for group 3; P = 0.09). Peak MBF (1.58 +/- 0.49 mL/min/g for group 1, 1.72 +/- 0.46 mL/min/g for group 2, and 1.97 +/- 0.32 mL/min/g for group 3; P = 0.14) and MFR (1.62 +/- 0.57 for group 1, 1.90 +/- 0.31 for group 2, and 2.27 +/- 0.51 for group 3; P = 0.01) were lower in the nonobstructive and higher in the latent HCM group. LVOTGs demonstrated no significant correlation with any flow dynamics. In a multivariate regression analysis, maximal wall thickness was the only significant predictor for reduced peak MBF (beta = -0.45, P = 0.003) and MFR (beta = -0.63, P = 0.0001). CONCLUSION: Maximal wall thickness was identified as the strongest predictor of impaired dipyridamole-induced hyperemia and flow reserve in our study, whereas outflow tract obstruction was not an independent determinant. PMID- 22315441 TI - Risk stratification of gallbladder polyps (1-2 cm) for surgical intervention with 18F-FDG PET/CT. AB - We assessed the value of (18)F-FDG uptake in the gallbladder polyp (GP) in risk stratification for surgical intervention and the optimal cutoff level of the parameters derived from GP (18)F-FDG uptake for differentiating malignant from benign etiologies in a select, homogeneous group of patients with 1- to 2-cm GPs. METHODS: Fifty patients with 1- to 2-cm GPs incidentally found on the CT portion of PET/CT were retrospectively analyzed. All patients had histologic diagnoses. GP (18)F-FDG activity was visually scored positive (>=liver) or negative (1 month) sick leave. Pre-existent heart disease odds ratio (OR) 4.50; confidence interval (CI) 1.27-16.09), hospitalization in the acute phase (OR 3.99; 95% CI 2.15-7.43) and smoking (OR 1.69; 95% CI 1.01-2.84) were significant predictors for long-term absence. Of the patients who resumed work, 9% were-at the time of completing the questionnaire-still unable to function at pre-infection levels due to fatigue or concentration problems. Of the respondents, 40% reported persisting physical symptoms at the time of follow-up. Fatigue (20%) was most frequently reported. Daily activities were affected in 30% of cases. CONCLUSIONS: Q-fever poses a serious persisting long-term burden on patients and society. PMID- 22315460 TI - Seasonal and pandemic influenza vaccine: recommendations to families of at-risk children during the 2009-10 season. AB - We performed a study in three Italian regions to evaluate the association between provided recommendations and immunization uptake of the two influenza vaccines in children with chronic diseases. We interviewed families of 119 at-risk children, collecting information regarding recommendations and immunizations against pandemic and seasonal influenza. In total 60.5% of children had received seasonal influenza vaccine, 38.7% had received pandemic influenza vaccine and 33.6% had not been vaccinated. The majority of immunized children had received specific recommendations by a physician. Physicians involved in the management of children with chronic diseases should actively recommend influenza immunization. PMID- 22315461 TI - The association between socio-demographic characteristics and perceived stress among residents in a deprived neighbourhood in Denmark. AB - BACKGROUND: It is known that stress is associated with various negative health outcomes, and higher levels are found among people with low socio-economic status (SES) compared with those better-off. Evidence of the characteristics of deprived neighbourhoods with negative impact on health and stress is accumulating while little is known about the stress variation by the socio-demographic characteristics of the dwellers. The present study aimed to investigate how stress varies by socio-demographic characteristics of the residents in a deprived neighbourhood. METHODS: The data used in this article were collected in the spring 2009. The 1160 participants, aged 16-104 years were randomly selected among the residents in a deprived neighbourhood in Esbjerg, Denmark. The survey was conducted through telephone and face to face interviews. Multiple linear regression analyses were carried on to examine the association of perceived stress with age, gender, ethnicity, education, civil status, economy, unemployment, sick leave, social deprivation and loneliness. RESULTS: The results show higher levels of stress among women, immigrants, poor and lonely compared with their counterparts. Stress decreases as the economy situation improves and people get old. Education, civil status and unemployment, initially significant, lost power in association with stress when income and economic deprivation were taken into account. CONCLUSION: The results of this study suggest that variation in the stress levels across socio-demographic characteristics may have specific features among people in the low SES hierarchy, dwellers of a deprived neighbourhood. PMID- 22315462 TI - Ethnic differences in weight retention after pregnancy: the ABCD study. AB - BACKGROUND: Postpartum weight retention contributes to the development of overweight and obesity in women of childbearing age and is more pronounced in ethnic minority groups. This study examined ethnic differences in postpartum weight retention and the explanatory role of socio-economic status (SES), mental health and lifestyle. METHODS: In the Amsterdam Born Children and their Development (ABCD) study, a large multi-ethnic cohort study conducted in The Netherlands, women filled out questionnaires in the first trimester of pregnancy and 3-5 months postpartum. A total of 4213 women provided data on weight gain, ethnicity, SES, mental health and lifestyle during and after pregnancy. Postpartum weight retention was defined as a difference of >=5 kg between self reported pre-pregnancy and postpartum weight. The influence of ethnicity on postpartum weight retention was assessed in logistic regression analyses. Whether the role of ethnicity was attenuated by adding SES, mental health and lifestyle factors were subsequently investigated. RESULTS: Marked differences in weight change during and after pregnancy were found between ethnic groups. Turkish women had significantly more weight retention than Dutch women. This difference could not be explained by other factors. CONCLUSION: In the prevention of postpartum weight retention, no single approach seems applicable to all ethnic groups. During pregnancy, health professionals should focus on Turkish women in particular, as they appear to have the highest risk of weight retention. PMID- 22315463 TI - Association of proximity to polluting industries, deprivation and mortality in small areas of the Basque Country (Spain). AB - BACKGROUND: The study is aimed at assessing social inequities in the location of polluting industries in the Basque Country, and at exploring if the effect on mortality of living near air polluting industries is modified by economic deprivation. METHODS: This is a cross-sectional ecological study that uses the census sections as analysis units. Mortality from all causes, lung cancer, respiratory diseases and ischaemic heart disease were studied. Ordinal logistic regression models were fitted to assess if proximity of census sections to polluting industries is associated with deprivation. Bayesian Poisson regression models were used to explore if the association between proximity to polluting industries and mortality is modified by socio-economic deprivation. RESULTS: Proximity to a polluting industry and deprivation are positively associated, showing a clear gradient across deprivation quintiles. In women, the risk associated with proximity to metal-processing industries grows as the deprivation of the area increases in the case of total and lung cancer mortality. In men, the interaction terms between proximity and deprivation are positive for total, ischaemic heart disease mortality, with a credibility level approaching 90%. High levels of deprivation are associated with greater risk of mortality, excepting lung cancer in women. CONCLUSION: There is a higher proportion of more deprived census sections around polluting industries in the Basque Country. Risks of mortality associated with proximity to polluting industries tend to be higher in more deprived areas. PMID- 22315464 TI - Can general practitioner commissioning deliver equity and excellence? Evidence from two studies of service improvement in the English NHS. AB - OBJECTIVES: To explore some of the key assumptions underpinning the continued development of general practitioner-led commissioning in health services. METHODS: Qualitative data from two studies of service improvement in the English NHS were considered against England's plans for GP-led commissioning. These data were collected through in-depth interviews with a total of 187 professionals and 99 people affected by services in 10 different primary care trust areas across England between 2008 and 2009. RESULTS: Internationally, GPs are seen to have a central position in health systems. In keeping with this, the English policy places emphasis on the 'pivotal role' of general practitioners, considered to be ideally placed to commission in the best interests of their patients. However, our evidence suggests that general practitioners do not always have a pivotal role for all patients. Moreover, it is planned that the new commissioning groups in England will not be subject to top-down performance management and this raises the question of how agreed quality standards will be met under the proposed new system. CONCLUSIONS: This paper questions the assumption that GPs are best placed to commission health services in a way that meets quality standards and leads to equitable outcomes. There is little evidence to suggest that GPs will succeed where others have failed and a risk that, without top-down performance management, service improvement will be patchy, leading to greater, not reduced, inequity. PMID- 22315465 TI - Investigating the governance of autonomous public hospitals in England: multi site case study of NHS foundation trusts. AB - OBJECTIVE: To investigate the external and internal governance of NHS foundation trusts (FTs), which have increased autonomy, and local members and governors unlike other NHS trusts. METHODS: In depth, three-year case studies of four FTs; and analysis of national quantitative data on all FT hospitals and NHS Trust hospitals to give national context. Data included 111 interviews with managers, clinicians, governors and members, and local purchasers; observation of meetings; and analysis of FTs' documents. RESULTS: The four case study FTs were similar to other FTs. They had used their increased autonomy to develop more business-like practices. The FT regulator, Monitor, intervened only when there were reported problems in FT performance. National targets applying to the NHS also had a large effect on FT behaviour. FTs saw themselves as part of the local health economy and tried to maintain good relationships with local organisations. Relationships between governors and the FTs' executives were still developing, and not all governors felt able to hold their FT to account. The skills and experience of staff members and governors were under-used in the new governance structures. CONCLUSIONS: It is easier to increase autonomy for public hospitals than to increase local accountability. Hospital managers are likely to be interested in making decisions with less central government control, whilst mechanisms for local accountability are notoriously difficult to design and operate. Further consideration of internal governance of FTs is needed. In a deteriorating financial climate, FTs should be better placed to make savings, due to their more business-like practices. PMID- 22315466 TI - Cancelled surgeries and payment by results in the English National Health Service. AB - OBJECTIVES: To model the frequency of 'last minute' cancellations of planned elective procedures in the English NHS with respect to the patient and provider factors that led to these cancellations. METHODS: A dataset of 5,288,604 elective patients spell in the English NHS from January 1st, 2007 to December 31st, 2007 was extracted from the Hospital Episode Statistics. A binary dependent variable indicating whether or not a patient had a Health Resource Group coded as S22- 'Planned elective procedure not carried out'--was modeled using a probit regression estimated via maximum likelihood including patient, case and hospital level covariates. RESULTS: Longer waiting times and being admitted on a Monday were associated with a greater rate of cancelled procedures. Male patients, patients from lower socio-economic groups and older patients had higher rates of cancelled procedures. There was significant variation in cancellation rates between hospitals; Foundation Trusts and private facilities had the lowest cancellation rates. CONCLUSIONS: Further research is needed on why Foundation Trusts exhibit lower cancellation rates. Hospitals with relatively high cancellation rates should be encouraged to tackle this problem. Further evidence is needed on whether hospitals are more likely to cancel operations where the procedure tariff is lower than the S22 tariff as this creates a perverse incentive to cancel. Understanding the underlying causes of why male, older and patients from lower socio-economic groups are more likely to have their operations cancelled is important to inform the appropriate policy response. This research suggests that interventions designed to reduce cancellation rates should be targeted to high-cancellation groups. PMID- 22315467 TI - Can physicians accurately predict which patients will lose weight, improve nutrition and increase physical activity? AB - BACKGROUND: Physician counselling may help patients increase physical activity, improve nutrition and lose weight. However, physicians have low outcome expectations that patients will change. The aims are to describe the accuracy of physicians' outcome expectations about whether patients will follow weight loss, nutrition and physical activity recommendations. The relationships between physician outcome expectations and patient motivation and confidence also are assessed. METHODS: This was an observational study that audio recorded encounters between 40 primary care physicians and 461 of their overweight or obese patients. We surveyed physicians to assess outcome expectations that patients will lose weight, improve nutrition and increase physical activity after counselling. We assessed actual patient change in behaviours from baseline to 3 months after the encounter and changes in motivation and confidence from baseline to immediately post-encounter. RESULTS: Right after the visit, ~55% of the time physicians were optimistic that their individual patients would improve. Physicians were not very accurate about which patients actually would improve weight, nutrition and physical activity. More patients had higher confidence to lose weight when physicians thought that patients would be likely to follow their weight loss recommendations. CONCLUSIONS: Physicians are moderately optimistic that patients will follow their weight loss, nutrition and physical activity recommendations. Patients might perceive physicians' confidence in them and thus feel more confident themselves. Physicians, however, are not very accurate in predicting which patients will or will not change behaviours. Their optimism, although helpful for patient confidence, might make physicians less receptive to learning effective counselling techniques. PMID- 22315468 TI - Improved radiological assessment of neonatal feeding tubes. AB - BACKGROUND: In about one-fifth of radiographs performed in neonates, no exact gastric feeding tube position can be defined. OBJECTIVES: To determine whether injection of air via feeding tube before taking radiographs improves radiological assessment of its position. METHODS: In the study group (n=153), air was injected via gastric feeding tube before taking a radiograph. The tube position on radiographs was compared with a blinded control group (n=381) with no injection of air. RESULTS: The definition of exact gastric tube position was possible in 95% of the study group compared with 78% in the control group (p<0.001). CONCLUSION: Injection of air before taking a radiograph significantly improves the definition of exact gastric feeding tube position in neonates. PMID- 22315469 TI - Functional neuroimaging demonstrates that ghrelin inhibits the central nervous system response to ingested lipid. AB - OBJECTIVE: Gut-derived humoural factors activate central nervous system (CNS) mechanisms controlling energy intake and expenditure, and autonomic outflow. Ghrelin is secreted from the stomach and stimulates food intake and gastric emptying, but the relevant mechanisms are poorly understood. Nutrient-activated CNS systems can be studied in humans by physiological/pharmacological MRI (phMRI). This method has been used to examine the CNS responses to exogenous ghrelin. DESIGN: phMRI was used to study the CNS responses in healthy people to a ghrelin bolus (0.3 nmol/kg, intravenous) in the post-prandial state, and an intravenous infusion of ghrelin (1.25 pmol/kg/min) alone and after intragastric lipid (dodecanoate, C12) in people who have fasted. RESULTS: A ghrelin bolus decreased the blood oxygenation level dependent (BOLD) signal detected by phMRI in feeding-activated areas of the CNS in the post-prandial state. Infusion of ghrelin reversed the effect of C12 in delaying gastric emptying but had no effect on hunger. Intragastric C12 caused strong bilateral activation of a matrix of CNS areas, including the brain stem, hypothalamus and limbic areas which was attenuated by exogenous ghrelin. Ghrelin infusion alone had a small but significant stimulatory effect on CNS BOLD signals. CONCLUSION: Ghrelin inhibits activation of the hypothalamus and brain stem induced by ingested nutrients, suggesting a role in suppression of gut-derived satiety signals in humans. PMID- 22315470 TI - A major advance in ex vivo intestinal organ culture. PMID- 22315471 TI - Standard endoscopy with random biopsies versus narrow band imaging targeted biopsies in Barrett's oesophagus: a prospective, international, randomised controlled trial. AB - BACKGROUND: White light endoscopy with random biopsies is the standard for detection of intestinal metaplasia (IM) and neoplasia in patients with Barrett's oesophagus (BO). Narrow band imaging (NBI) highlights surface patterns that correlate with IM and neoplasia in BO. OBJECTIVE: To compare high-definition white light (HD-WLE) and NBI for detection of IM and neoplasia in BO. DESIGN: International, randomised, crossover trial comparing HD-WLE and NBI. Patients referred for BO screening/surveillance at three tertiary referral centres were prospectively enrolled and randomised to HD-WLE or NBI followed by other procedures in 3-8 weeks. During HD-WLE, four quadrant biopsies every 2 cm, together with targeted biopsies of visible lesions (Seattle protocol), were obtained. During NBI examination, mucosal and vascular patterns were noted and targeted biopsies were obtained. All biopsies were read by a single expert gastrointestinal pathologist in a blinded fashion. RESULTS: 123 patients with BO (mean age 61; 93% male; 97% Caucasian) with mean circumferential and maximal extents of 1.8 and 3.6 cm, respectively, were enrolled. Both HD-WLE and NBI detected 104/113 (92%) patients with IM, but NBI required fewer biopsies per patient (3.6 vs 7.6, p<0.0001). NBI detected a higher proportion of areas with dysplasia (30% vs 21%, p=0.01). During examination with NBI, all areas of high grade dysplasia and cancer had an irregular mucosal or vascular pattern. CONCLUSIONS: NBI targeted biopsies can have the same IM detection rate as an HD WLE examination with the Seattle protocol while requiring fewer biopsies. In addition, NBI targeted biopsies can detect more areas with dysplasia. Regular appearing NBI surface patterns did not harbour high-grade dysplasia/cancer, suggesting that biopsies could be avoided in these areas. PMID- 22315473 TI - Evaluating Labour's market reforms, 2002-10. AB - Starting in 2002, the UK Labour government of 1997-2010 introduced a series of changes to the National Health Service (NHS) in England designed to increase individual NHS patient choice of place of elective hospital care and competition among public and private providers of elective hospital services for NHS-funded patients. In 2006, the Department of Health initiated the Health Reform Evaluation Programme (HREP) to assess the impact of the changes. The changes broadly had the effects that proponents had predicted but the effects were mostly modest. Most of the undesirable impacts feared by critics appeared not to have materialized to any discernible extent, at least by early in 2010. Labour's market appeared to have generated stronger incentives for quality and efficiency than its 1990 s predecessor with no obvious detriment to equity of access. However, this high level conclusion conceals a far more nuanced and complex picture of both the process of implementation and the impact of the changes, as the papers in this supplement drawn from the HREP show. PMID- 22315472 TI - A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. AB - OBJECTIVE: Gastric cancer is a major gastrointestinal malignancy for which targeted therapies are emerging as treatment options. This study sought to identify the most prevalent molecular targets in gastric cancer and to elucidate systematic patterns of exclusivity and co-occurrence among these targets, through comprehensive genomic analysis of a large panel of gastric cancers. DESIGN: Using high-resolution single nucleotide polymorphism arrays, copy number alterations were profiled in a panel of 233 gastric cancers (193 primary tumours, 40 cell lines) and 98 primary matched gastric non-malignant samples. For selected alterations, their impact on gene expression and clinical outcome were evaluated. RESULTS: 22 recurrent focal alterations (13 amplifications and nine deletions) were identified. These included both known targets (FGFR2, ERBB2) and also novel genes in gastric cancer (KLF5, GATA6). Receptor tyrosine kinase (RTK)/RAS alterations were found to be frequent in gastric cancer. This study also demonstrates, for the first time, that these alterations occur in a mutually exclusive fashion, with KRAS gene amplifications highlighting a clinically relevant but previously underappreciated gastric cancer subgroup. FGFR2-amplified gastric cancers were also shown to be sensitive to dovitinib, an orally bioavailable FGFR/VEGFR targeting agent, potentially representing a subtype specific therapy for FGFR2-amplified gastric cancers. CONCLUSION: The study demonstrates the existence of five distinct gastric cancer patient subgroups, defined by the signature genomic alterations FGFR2 (9% of tumours), KRAS (9%), EGFR (8%), ERBB2 (7%) and MET (4%). Collectively, these subgroups suggest that at least 37% of gastric cancer patients may be potentially treatable by RTK/RAS directed therapies. PMID- 22315474 TI - What was the programme theory of New Labour's Health System Reforms? AB - OBJECTIVES: To examine whether the Health System Reforms delivered the promise of being a coherent and mutually supporting reform programme; to identify the underlying programme theory of the reform programme; to reflect on whether lessons have been learned. METHODS: Documentary analysis mapping the implicit and explicit programme theories about how the reforms intended to achieve its goals and outcomes. Semi-structured interviews with policy-makers to further understand the programme theory. RESULTS: The Health System Reforms assumed a 'one size fits all' approach to policy implementation with little recognition that some contexts can be more receptive than others. There was evidence of some policy evolution and rebalancing between the reform streams as policy-makers became aware of some perverse incentives and unforeseen consequences. Later elements aimed to restore balance to the system. CONCLUSIONS: The Health System Reforms do not appear to comprise a coherent and mutually supportive set of levers and incentives. They appear unbalanced with the centre of gravity favouring suppliers over commissioners. However, recent reform changes have sought to redress this imbalance to some extent, suggesting that lessons have been learned and policies have been adapted over time. PMID- 22315475 TI - Commissioning processes in primary care trusts: a repeated cross-sectional survey of health care commissioners in England. AB - OBJECTIVES: To determine the extent to which primary care trusts (PCTs) in England employed processes associated with quality commissioning and to assess whether changes occurred in these processes during a policy drive to improve commissioning. METHODS: Telephone surveys of PCT managers leading commissioning for diabetes, chronic obstructive pulmonary disease (COPD), coronary heart disease (CHD), and emergency and urgent care in all 152 PCTs in both 2009 and 2010. RESULTS: The response rate was 51% (77/152) of PCTs in 2009 and 60% (91/152) in 2010. Two-thirds of commissioners had commissioned initiatives starting in the previous financial year. Over half of initiatives starting in 2008/09 had been instigated by the PCT alone. This reduced to a third in 2010, showing a shift towards partnership working. Commissioners reported that a large proportion of initiatives had been developed and shaped with the involvement of general practitioners (GPs) with direct links to the PCT and of specialist clinicians (70%), but that a lower proportion of initiatives had involvement from other GPs (40%). Patients or the public were less likely to be involved in initiatives than clinicians, but there was evidence of increasing involvement over the two years from 35% (52/149) to 51% (67/132) of initiatives. There was no evidence of changes in whether needs assessment was undertaken, how evidence was used or how initiatives were led and performance managed. CONCLUSIONS: PCT commissioners reported clinical engagement in the majority of commissioning initiatives, a shift towards partnership commissioning, and increased involvement of patients and public in the development of initiatives. The new model of commissioning in England through clinical commissioning groups will need to improve on these processes if it is to demonstrate a higher quality approach to commissioning. PMID- 22315476 TI - Implementing world class commissioning competencies. AB - BACKGROUND: The world class commissioning (WCC) programme was introduced in the English NHS in 2007 to develop primary care trust (PCT) commissioning of health services. There has been limited evaluation of health commissioning initiatives over the years and in particular little is known about how commissioners interpret and implement initiatives and guidance intended to strengthen commissioning. This research explores the development and implementation of WCC and draws implications for future commissioning arrangements. METHODS: This research draws on interviews with key informants (n = 6) and a literature review to analyse the aims of, and stimulus for, WCC. In-depth interviews (n = 38) were conducted in three PCTs in the north of England in 2009 to analyse the interpretation and implementation of WCC. RESULTS: The aims and rationale of WCC, in particular, the specification of commissioning skills and the aspirations to improve health outcomes, were largely welcomed and supported by interviewees. However, the implementation of WCC posed a number of challenges, including: availability of resources and knowledge; lack of a supportive organizational culture and networks; and the dominance of central government control. CONCLUSIONS: The findings have implications for emerging clinical commissioning groups (CCGs) in the English NHS. Specifically, the research highlights the need for a system-wide approach to improving commissioning, including appropriately aligned policy and objectives underpinned by a co-ordinated and supportive organizational culture. PMID- 22315477 TI - Can competition improve outcomes in UK health care? Lessons from the past two decades. AB - UK governments of all political colours have sought to improve productivity in health care by introducing pro-competitive reforms in the National Health Service (NHS) during the last two decades. The first wave of reform operated from 1991 to 1997. The second wave was introduced in England only in the mid 2000s. In 2010, further reform in England, intended to increase the extent of competition, was proposed by the Coalition administration. But the effect of competition on productivity in health care and in particular on the quality of health care remains a contested issue. This paper reviews the evidence, focusing on robust and recent evidence, on the use of competition as a mechanism for improving quality. The consensus is that competition will increase quality in health care, but that institutional details matter. Given this, we end by discussing whether the current plans to make the buyers of care family doctors and other professionals and to allow some local price variation are likely to be beneficial in the UK context of full public funding for health care. PMID- 22315478 TI - Effects of the Blair/Brown NHS reforms on socioeconomic equity in health care. AB - The central objectives of the 'Blair/Brown' reforms of the English NHS in the 2000s were to reduce hospital waiting times and improve the quality of care. However, critics raised concerns that the choice and competition elements of reform might undermine socioeconomic equity in health care. By contrast, the architects of reform predicted that accelerated growth in NHS spending combined with increased patient choice of hospital would enhance equity for poorer patients. This paper draws together and discusses the findings of three large scale national studies designed to shed empirical light on this issue. Study one developed methods for monitoring change in neighbourhood level socioeconomic equity in the utilization of health care, and found no substantial change in equity between 2001-02 and 2008-09 for non-emergency hospital admissions, outpatient admissions (from 2004-05) and a basket of specific hospital procedures (hip replacement, senile cataract, gastroscopy and coronary revascularization). Study two found that increased competition between 2003-04 and 2008-09 had no substantial effect on socioeconomic equity in health care. Study three found that potential incentives for public hospitals to select against socioeconomically disadvantaged hip replacement patients were small, compared with incentives to select against elderly and co-morbid patients. Taken together, these findings suggest that the Blair/Brown reforms had little effect on socioeconomic equity in health care. This may be because the 'dose' of competition was small and most hospital services continued to be provided by public hospitals which did not face strong incentives to select against socioeconomically-disadvantaged patients. PMID- 22315479 TI - Prevalence and benefits of care plans and care planning for people with long-term conditions in England. AB - OBJECTIVES: Among patients with long-term conditions, to determine the prevalence and benefits of care planning discussions and of care plans. METHODS: Data from the 2009/10 General Practice Patient Survey, a cross sectional survey of 5.5 million patients in England. Outcomes were patient reports of: care planning discussions; perceived benefit from care planning discussions and resultant care plans. Patient and practice variables were included in multilevel logistic regression to investigate predictors of each outcome. RESULTS: Half the respondents (49%) reported a long-term condition and were eligible to answer the care planning questions. Of these, 84% reported having a care planning discussion during the last 12 months and most reported some benefit. Only 12% who reported a care planning discussion also reported being told they had a care plan. Patients who reported having a care plan were more likely to report benefits from care planning discussions. Several factors predicted the reporting of care planning and care plans of which the most important was patients' reports of the quality of interpersonal care. CONCLUSIONS: There is a gap between policy and current practice which might reflect uncertainty as to the benefits of care plans. There is, therefore, a need for rigorous evaluation of care plans. PMID- 22315480 TI - Effectiveness of sulpiride in adult patients with schizophrenia. AB - The objective of this study is to compare the effectiveness among sulpiride, risperidone, olanzapine, and haloperidol by evaluating the persistence of drug use. A retrospective cohort study was conducted by analyzing the National Health Insurance Research Database of Taiwan. Patients with schizophrenia aged 18-65 years and newly prescribed with a single oral antipsychotic medication between years 2003 and 2008 were included. The primary outcome was the persistence of antipsychotic agents by calculating the treatment duration till treatment changed. All defined treatment changes were also analyzed separately, including discontinuation, switching, augmentation, and hospitalization. A total of 1324 eligible patients were included, with an average age of 36 years old and approximately 45% of them were female. The most prevalent antipsychotic use was risperidone (42.1%), followed by sulpiride (36.0%), haloperidol (14.2%), and olanzapine (7.7%). After adjusting for patient demographics, mental illness characteristics, and propensity score, the Cox regression models found that the risk of nonpersistence was significantly higher in patients receiving risperidone (hazard ratio [HR], 1.22; 95% CI, 1.06-1.40), haloperidol (HR, 1.98; 95% CI, 1.63 2.40), and olanzapine (HR, 1.34; 95% CI, 1.07-1.68), as compared with sulpiride, suggesting the effectiveness of sulpiride was better than the other 3 antipsychotics. Therefore, this study would provide strong grounds for a properly conducted randomized controlled trial of the clinical- and cost-effectiveness of sulpiride vs atypical antipsychotics. PMID- 22315481 TI - Evidence for the criterion validity and clinical utility of the Pathological Narcissism Inventory. AB - In this study, the authors evaluated aspects of criterion validity and clinical utility of the grandiosity and vulnerability components of the Pathological Narcissism Inventory (PNI) using two undergraduate samples (N = 299 and 500). Criterion validity was assessed by evaluating the correlations of narcissistic grandiosity and narcissistic vulnerability with established indices of normal personality traits, psychopathology and clinical concerns, and pathological personality traits. Overall, the pattern of correlations supported the convergent and discriminant validity of grandiose and vulnerable conceptualizations of pathological narcissism as measured by the PNI. Clinical utility was assessed by evaluating the extent to which clinicians without specific training in pathological narcissism as well as clinicians with expertise in pathological narcissism could accurately predict the correlates of PNI grandiosity and vulnerability with normal and pathological personality traits and psychopathology. The r(contrast-cv) coefficient provided a global index of accuracy in clinicians' predictions that was more fully elaborated by examining systematic discrepancies across groups. Overall, novice and expert clinicians were generally able to predict criterion correlations, with some exceptions (e.g., counter to predictions, pathological narcissism was negatively associated with treatment resistance). These results provide further evidence regarding the validity and utility of the narcissistic grandiosity and narcissistic vulnerability constructs as measured by the PNI. PMID- 22315482 TI - Psychometric evaluation of the thought-action fusion scale in a large clinical sample. AB - This study examined the psychometric properties of the 19-item Thought-Action Fusion (TAF) Scale, a measure of maladaptive cognitive intrusions, in a large clinical sample (N = 700). An exploratory factor analysis (n = 300) yielded two interpretable factors: TAF Moral (TAF-M) and TAF Likelihood (TAF-L). A confirmatory bifactor analysis was conducted on the second portion of the sample (n = 400) to account for possible sources of item covariance using a general TAF factor (subsuming TAF-M) alongside the TAF-L domain-specific factor. The bifactor model provided an acceptable fit to the sample data. Results indicated that global TAF was more strongly associated with a measure of obsessive compulsiveness than measures of general worry and depression, and the TAF-L dimension was more strongly related to obsessive-compulsiveness than depression. Overall, results support the bifactor structure of the TAF in a clinical sample and its close relationship to its neighboring obsessive-compulsiveness construct. PMID- 22315483 TI - Kikuchi-Fujimoto disease: a 15-year analysis at a children's hospital in the United States. PMID- 22315484 TI - Invasive pneumococcal disease in infants younger than 60 days. AB - OBJECTIVE: To review the epidemiology and clinical course of invasive pneumococcal diseases of infants younger than 60 days. STUDY DESIGN: All Streptococcus pneumoniae strains isolated from blood and cerebrospinal fluid cultures of infants below the age of 60 days during the years 1999-2009 were included in this study. Demographic, clinical, and laboratory data were collected from medical records. RESULTS: In all, 24 cases of pneumococcal invasive infections were identified. The primary diagnoses were bacteremia without a focus (n = 13), meningitis (n = 6), bacteremia with otitis media (n = 3), and joint infection with bacteremia (n = 2). Only one of the serotypes found is included in the heptavalent pneumococcal conjugated vaccine (PCV7). CONCLUSIONS: Streptococcus pneumoniae should be considered and treated empirically in infants with suspected invasive bacterial disease during the first 60 days of life. Routine vaccination with PCV7 in not expected to substantially reduce the incidence of invasive pneumococcal disease in Israeli infants of this age as a result of herd immunity. PMID- 22315485 TI - Behcet disease presenting with pseudomembranous colitis and progression to neurological involvement: case report and review of the literature. PMID- 22315486 TI - A multicenter phase II trial (SAKK 36/06) of single-agent everolimus (RAD001) in patients with relapsed or refractory mantle cell lymphoma. AB - BACKGROUND: Mantle cell lymphoma accounts for 6% of all B-cell lymphomas and is generally incurable. It is characterized by the translocation t(11;14) leading to cyclin D1 over-expression. Cyclin D1 is downstream of the mammalian target of rapamycin threonine kinase and can be effectively blocked by mammalian target of rapamycin inhibitors. We set out to examine the single agent activity of the orally available mammalian target of rapamycin inhibitor everolimus in a prospective, multicenter trial in patients with relapsed or refractory mantle cell lymphoma (NCT00516412). DESIGN AND METHODS: Eligible patients who had received a maximum of three prior lines of chemotherapy were given everolimus 10 mg for 28 days (one cycle) for a total of six cycles or until disease progression. The primary endpoint was the best objective response. Adverse reactions, progression-free survival and molecular response were secondary endpoints. RESULTS: Thirty-six patients (35 evaluable) were enrolled and treatment was generally well tolerated with Common Terminology Criteria grade >= 3 adverse events (>5%) including anemia (11%), thrombocytopenia (11%) and neutropenia (8%). The overall response rate was 20% (95% CI: 8-37%) with two complete remissions and five partial responses; 49% of the patients had stable disease. At a median follow-up of 6 months, the median progression-free survival was 5.5 months (95% CI: 2.8-8.2) overall and 17.0 (6.4-23.3) months for 18 patients who received six or more cycles of treatment. Three patients achieved a lasting complete molecular response, as assessed by polymerase chain reaction analysis of peripheral blood. CONCLUSIONS: Everolimus as a single agent is well tolerated and has anti-lymphoma activity in relapsed or refractory mantle cell lymphoma. Further studies of everolimus in combination with chemotherapy or as a single agent for maintenance treatment are warranted. PMID- 22315487 TI - Impact of body-mass index on the outcome of adult patients with acute myeloid leukemia. AB - BACKGROUND: Obesity increases the risk of treatment-related complications and reduces survival in children with acute myeloid leukemia. Little is known about the impact of obesity on the outcome of adult patients with acute myeloid leukemia. DESIGN AND METHODS: We compared the baseline characteristics and effect on treatment and survival in 1,974 previously untreated adult patients with acute myeloid leukemia undergoing treatment, according to international classification of body-mass index. RESULTS: The median body-mass index was 26.7 (15.5-61) and 63% of patients were overweight/obese. After adjustment for other confounders, such as age, gender, performance status, karyotype, white blood cell, platelet and peripheral blast counts, obese patients had better complete remission rates (P=0.0046), lower rates of resistant disease (P=0.038) but similar rates of survival and severe adverse events. CONCLUSIONS: In the treatment of acute myeloid leukemia in adults, obesity was associated with increased response rates and no apparent increase in toxicity. Obesity should not, therefore, be a criterion for excluding patients from aggressive therapy. PMID- 22315488 TI - The impact of cyclin D1 mRNA isoforms, morphology and p53 in mantle cell lymphoma: p53 alterations and blastoid morphology are strong predictors of a high proliferation index. AB - BACKGROUND: Mantle cell lymphoma is a clinically heterogeneous disease characterized by overexpression of cyclin D1 protein. Blastoid morphology, high proliferation, and secondary genetic aberrations are markers of aggressive behavior. Expression profiling of mantle cell lymphoma revealed that predominance of the 3'UTR-deficient, short cyclin D1 mRNA isoform was associated with high cyclin D1 levels, a high "proliferation signature" and poor prognosis. DESIGN AND METHODS: Sixty-two cases of mantle cell lymphoma were analyzed for cyclin D1 mRNA isoforms and total cyclin D1 levels by real-time reverse transcriptase polymerase chain reaction, and TP53 alterations were assessed by immunohistochemistry and molecular analysis. Results were correlated with proliferation index and clinical outcome. RESULTS: Predominance of the short cyclin D1 mRNA was found in 14 (23%) samples, including four with complete loss of the standard transcript. TP53 alterations were found in 15 (24%) cases. Predominance of 3'UTR-deficient mRNA was significantly associated with high cyclin D1 mRNA levels (P=0.009) and more commonly found in blastoid mantle cell lymphoma (5/11, P=0.060) and cases with a proliferation index of >20% (P=0.026). Both blastoid morphology (11/11, P<0.001) and TP53 alterations (15/15, P<0.001) were significantly correlated with a high proliferation index. A proliferation index of 10% was determined to be a significant threshold for survival in multivariate analysis (P=0.01). CONCLUSIONS: TP53 alterations are strongly associated with a high proliferation index and aggressive behavior in mantle cell lymphoma. Predominance of the 3'UTR deficient transcript correlates with higher cyclin D1 levels and may be a secondary contributing factor to high proliferation, but failed to reach prognostic significance in this study. PMID- 22315489 TI - Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes: results of a European LeukemiaNET study. AB - BACKGROUND: The current World Health Organization classification of myelodysplastic syndromes is based morphological evaluation of bone marrow dysplasia. In clinical practice, the reproducibility of the recognition of dysplasia is usually poor especially in cases that lack specific markers such as ring sideroblasts and clonal cytogenetic abnormalities. DESIGN AND METHODS: We aimed to develop and validate a flow cytometric score for the diagnosis of myelodysplastic syndrome. Four reproducible parameters were analyzed: CD34(+) myeloblast-related and B-progenitor-related cluster size (defined by CD45 expression and side scatter characteristics CD34(+) marrow cells), myeloblast CD45 expression and granulocyte side scatter value. The study comprised a "learning cohort" (n=538) to define the score and a "validation cohort" (n=259) to confirm its diagnostic value. RESULTS: With respect to non-clonal cytopenias, patients with myelodysplastic syndrome had increased myeloblast-related cluster size, decreased B-progenitor-related cluster size, aberrant CD45 expression and reduced granulocyte side scatter (P<0.001). To define the flow cytometric score, these four parameters were combined in a regression model and the weight for each variable was estimated based on coefficients from that model. In the learning cohort a correct diagnosis of myelodysplastic syndrome was formulated in 198/281 cases (sensitivity 70%), while 18 false-positive results were noted among 257 controls (specificity 93%). Sixty-five percent of patients without specific markers of dysplasia (ring sideroblasts and clonal cytogenetic abnormalities) were correctly classified. A high value of the flow cytometric score was associated with multilineage dysplasia (P=0.001), transfusion dependency (P=0.02), and poor-risk cytogenetics (P=0.04). The sensitivity and specificity in the validation cohort (69% and 92%, respectively) were comparable to those in the learning cohort. The likelihood ratio of the flow cytometric score was 10. CONCLUSIONS: A flow cytometric score may help to establish the diagnosis of myelodysplastic syndrome, especially when morphology and cytogenetics are indeterminate. PMID- 22315490 TI - CD34+ gene expression profiling of individual children with very severe aplastic anemia indicates a pathogenic role of integrin receptors and the proapoptotic death ligand TRAIL. AB - BACKGROUND Very severe aplastic anemia is characterized by a hypoplastic bone marrow due to destruction of CD34(+) stem cells by autoreactive T cells. Investigation of the pathomechanism by patient-specific gene expression analysis of the attacked stem cells has previously been impractical because of the scarcity of these cells at diagnosis. DESIGN AND METHODS: Employing unbiased RNA amplification, patient-specific gene expression profiling was carried out for CD34(+) cells from patients newly diagnosed with very severe aplastic anemia (n=13), refractory anemia (n=8) and healthy controls (n=10). These data were compared to profiles of myelodysplastic disease (n=55), including refractory anemia (n=18). To identify possible targets of autoimmune attack, presence of autoreactive antibodies was tested in pre-therapeutic sera of patients with very severe aplastic anemia (n=19). RESULTS: CD34(+) gene expression profiling distinguished between healthy controls, children with aplastic or refractory anemia and clonal disease. Interferon stimulated genes such as the apoptosis inducing death ligand TRAIL were strongly up-regulated in CD34(+) cells of patients with aplastic anemia, in particular in patients responding to immunosuppressive treatment. In contrast, mRNA expression of integrin GPVI and the integrin complexes GPIa/IIa, GPIIb/IIIa, GPIB/GPIX/GPV was significantly down regulated and corresponding antibodies were detected in 7 of 11 profiled patients and in 11 of 19 aplastic anemia patients. CONCLUSIONS As a potential diagnostic tool, patient-specific gene expression profiling of CD34(+) stem cells made it possible to make the difficult differential diagnosis of most patients with aplastic and refractory anemia. Profiling indicated a prognostic correlation of TRAIL expression and patient benefit from immunosuppressive therapy. Downregulation of integrin expression and concurrent presence of autoreactive anti-integrin-antibodies suggested a previously unrecognized pathological role of integrins in aplastic anemia. PMID- 22315491 TI - High-throughput molecular diagnosis of von Willebrand disease by next generation sequencing methods. AB - Genetic analysis of von Willebrand disease by von Willebrand factor gene sequencing has not yet become routine practice. Nevertheless, the prospects for molecular diagnosis have changed dramatically in recent years with the unveiling of next-generation sequencing platforms. With the goal of applying this technology to von Willebrand disease, we designed a strategy for von Willebrand factor gene enrichment and multiplexing based on short polymerase chain reactions. Forty patients were simultaneously analyzed enabling the identification of 43 mutations, including 36 substitutions, 2 intronic splice site mutations, 2 indels, and 3 deletions. By pooling patient genomic DNA before polymerase chain reaction enrichment, indexing samples with barcode tags, and re sequencing on the next-generation sequencing instrument, at least 350 patients and relatives per run can be simultaneously analyzed in a fast, inexpensive manner. This is one of the first reports in which this technology has been shown to be feasible for large-scale mutation screening by single gene re-sequencing. PMID- 22315492 TI - Immunohistochemical markers for tumor associated macrophages and survival in advanced classical Hodgkin's lymphoma. AB - A subset of patients with advanced classical Hodgkin's lymphoma is refractory to standard therapies. Therefore, it is relevant to identify new biologically-based prognostic markers. Recently, tumor associated macrophages have been proposed as a factor that predicts survival, although contradictory results have also been reported. Here we analyzed four macrophage markers (CD68, CD163, LYZ, and STAT1) using immunohistochemistry and automated quantification, in two independent series of advanced classical Hodgkin's lymphoma (n=266 and 103 patients, respectively). Our results did not confirm that specific macrophage immunohistochemical markers could be used as surrogates for gene expression profiling studies. Survival analyses did not show correlation between CD163, LYZ or STAT1 and either failure-free or disease-specific survival. There was an association between CD68 and disease-specific survival, but it was not consistent in both series. In conclusion, individual tumor associated macrophage markers cannot be used to predict outcome before technical standardization and prospective validation in independent series of patients with comparable stages and treatments. PMID- 22315493 TI - The small population of PIG-A mutant cells in myelodysplastic syndromes do not arise from multipotent hematopoietic stem cells. AB - BACKGROUND: Patients with paroxysmal nocturnal hemoglobinuria harbor clonal glycosylphosphatidylinositol-anchor deficient cells arising from a multipotent hematopoietic stem cell acquiring a PIG-A mutation. Many patients with aplastic anemia and myelodysplastic syndromes also harbor small populations of glycosylphosphatidylinositol-anchor deficient cells. Patients with aplastic anemia often evolve into paroxysmal nocturnal hemoglobinuria; however, myelodysplastic syndromes seldom evolve into paroxysmal nocturnal hemoglobinuria. Here, we investigate the origin and clonality of small glycosylphosphatidylinositol-anchor deficient cell populations in aplastic anemia and myelodysplastic syndromes. DESIGN AND METHODS: We used peripheral blood flow cytometry to identify glycosylphosphatidylinositol-anchor deficient blood cells, a proaerolysin-resistant colony forming cell assay to select glycosylphosphatidylinositol-anchor deficient progenitor cells, a novel T lymphocyte enrichment culture assay with proaerolysin selection to expand glycosylphosphatidylinositol-anchor deficient T lymphocytes, and PIG-A gene sequencing assays to identify and analyze PIG-A mutations in patients with aplastic anemia and myelodysplastic syndromes. RESULTS: Twelve of 15 aplastic anemia patients were found to harbor a small population of glycosylphosphatidylinositol-anchor deficient granulocytes; 11 of them were found to harbor a small population of glycosylphosphatidylinositol-anchor deficient erythrocytes, 10 patients were detected to harbor glycosylphosphatidylinositol anchor deficient T lymphocytes, and 3 of them were detected only after T lymphocyte enrichment in proaerolysin selection. PIG-A mutation analyses on 3 patients showed that all of them harbored a matching PIG-A mutation between CFU GM and enriched T lymphocytes. Two of 26 myelodysplastic syndromes were found to harbor small populations of glycosylphosphatidylinositol-anchor deficient granulocytes and erythrocytes transiently. Bone marrow derived CD34(+) cells from 4 patients grew proaerolysin-resistant colony forming cells bearing PIG-A mutations. No glycosylphosphatidylinositol-anchor deficient T lymphocytes were detected in myelodysplastic syndrome patients. CONCLUSIONS: In contrast to aplastic anemia and paroxysmal nocturnal hemoglobinuria, where PIG-A mutations arise from multipotent hematopoietic stem cells, glycosylphosphatidylinositol anchor deficient cells in myelodysplastic syndromes appear to arise from more committed progenitors. PMID- 22315494 TI - CBL mutations in myeloproliferative neoplasms are also found in the gene's proline-rich domain and in patients with the V617FJAK2. AB - BACKGROUND: Despite the discovery of the p.V617F in JAK2, the molecular pathogenesis of some chronic myeloproliferative neoplasms remains unclear. Although very rare, different studies have identified CBL (Cas-Br-Murine ecotropic retroviral transforming sequence) mutations in V617FJAK2-negative patients, mainly located in the RING finger domain. In order to determine the frequency of CBL mutations in these diseases, we studied different regions of all CBL family genes (CBL, CBLB and CBLC) in a selected group of patients with myeloproliferative neoplasms. We also included V617FJAK2-positive patients to check whether mutations in CBL and JAK2 are mutually exclusive events. DESIGN AND METHODS: Using denaturing high performance liquid chromatography, we screened for mutations in CBL, CBLB and CBLC in a group of 172 V617FJAK2-negative and 232 V617FJAK2-positive patients with myeloproliferative neoplasms not selected for loss of heterozygosity. The effect on cell proliferation of the mutations detected was analyzed on a 32D(FLT3) cell model. RESULTS: An initial screening of all coding exons of CBL, CBLB and CBLC in 44 V617FJAK2-negative samples revealed two new CBL mutations (p.C416W in the RING finger domain and p.A678V in the proline-rich domain). Analyses performed on 128 additional V617FJAK2-negative and 232 V617FJAK2-positive samples detected three CBL changes (p.T402HfsX29, p.P417R and p.S675C in two cases) in four V617FJAK2-positive patients. None of these mutations was found in 200 control samples. Cell proliferation assays showed that all of the mutations promoted hypersensitivity to interleukin-3 in 32D(FLT3) cells. CONCLUSIONS: Although mutations described to date have been found in the RING finger domain and in the linker region of CBL, we found a similar frequency of mutations in the proline-rich domain. In addition, we found CBL mutations in both V617FJAK2-positive (4/232; 1.7%) and negative (2/172; 1.2%) patients and all of them promoted hypersensitivity to interleukin-3. PMID- 22315495 TI - Plasma exposure of imatinib and its correlation with clinical response in the Tyrosine Kinase Inhibitor Optimization and Selectivity Trial. AB - BACKGROUND: This study evaluates the correlation between imatinib trough plasma concentrations (C(min)) and clinical response and safety in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase in the Tyrosine Kinase Inhibitor OPtimization and Selectivity (TOPS) trial. DESIGN AND METHODS: Patients were randomized 1:2 to 400 mg/day or 800 mg/day imatinib. Imatinib C(min) levels were collected at pre-dose before treatment, and at the end of months 1 (day 29), 6, 9, and 12. RESULTS: Imatinib C(min) were stable over time in the 400 mg/day dose arm, but showed a slight decrease in the 800 mg/day arm due to dose adjustments between months 1-6. The overall median imatinib C(min) levels were 1040, 1200, 1935, and 2690 ng/mL for the actual 300, 400, 600, and 800 mg/day doses, respectively. The rates of major molecular response (MMR) at 3, 6, 9, and 12 months, and complete cytogenetic response (CCyR) at 6 and 12 months were significantly lower among patients with the lowest imatinib C(min) levels at Day 29 (<1165 ng/mL, 25th percentile). There was an apparent association between high imatinib C(min) and the occurrence of grade 3/4 neutropenia and all-grade rash, diarrhea, arthralgia/myalgia, and all-cause edema. Conclusions Imatinib C(min) levels were relatively stable over time and proportional to the dose administered. Patients with an imatinib C(min) above 1165 ng/mL on Day 29 achieved MMR faster and had higher MMR and CCyR rates at 12 months. There appeared to be an association between imatinib C(min) and the frequency of some adverse events. This trial was registered at http://www.clinicaltrials.gov as NCT00124748. PMID- 22315496 TI - CD20 positive cells are undetectable in the majority of multiple myeloma cell lines and are not associated with a cancer stem cell phenotype. AB - Although new therapies have doubled the survival of multiple myeloma patients, this remains an incurable disease. It has been postulated that the so-called myeloma cancer stem cells would be responsible for tumor initiation and relapse but their unequivocal identification remains unclear. Here, we investigated in a panel of myeloma cell lines the presence of CD20(+) cells harboring a stem-cell phenotype. Thus, only a small population of CD20(dim+) cells (0.3%) in the RPMI 8226 cell line was found. CD20(dim+) RPMI-8226 cells expressed the plasma cell markers CD38 and CD138 and were CD19(-)CD27(-). Additionally, CD20(dim+) RPMI 8226 cells did not exhibit stem-cell markers as shown by gene expression profiling and the aldehyde dehydrogenase assay. Furthermore, we demonstrated that CD20(dim+) RPMI-8226 cells are not essential for CB17-SCID mice engraftment and show lower self-renewal potential than the CD20(-) RPMI-8226 cells. These results do not support CD20 expression for the identification of myeloma cancer stem cells. PMID- 22315497 TI - Bone marrow versus peripheral blood as the stem cell source for sibling transplants in acquired aplastic anemia: survival advantage for bone marrow in all age groups. AB - BACKGROUND: Bone marrow has been shown to be superior to peripheral blood, as a stem cell source, in young patients (<20 years of age) with acquired aplastic anemia undergoing a matched sibling transplant. The aim of this study was to test whether this currently also holds true for older patients with acquired aplastic anemia. DESIGN AND METHODS: We analyzed 1886 patients with acquired aplastic anemia who received a first transplant from a human leukocyte antigen identical sibling between 1999 and 2009, with either bone marrow (n=1163) or peripheral blood (n=723) as the source of stem cells. RESULTS: In multivariate Cox analysis negative predictors for survival were: patient's age over 20 years (RR 2.0, P<0.0001), an interval between diagnosis and transplantation of more than 114 days (RR 1.3, P=0.006), no anti-thymocyte globulin in the conditioning (RR 1.6, P=0.0001), a conditioning regimen other than cyclophosphamide (RR=1.3, P=0.008) and the use of peripheral blood as the source of stem cells (RR 1.6, P<0.00001). The survival advantage for recipients of bone marrow rather than peripheral blood was statistically significant in patients aged 1-19 years (90% versus 76% P<0.00001) as well as in patients aged over 20 years (74% versus 64%, P=0.001). The advantage for recipients of bone marrow over peripheral blood was maintained above the age of 50 years (69% versus 39%, P=0.01). Acute and chronic graft versus-host disease were more frequent in peripheral blood transplants. Major causes of death were graft-versus-host disease (2% versus 6% in bone marrow and peripheral blood recipients, respectively), infections (6% versus 13%), and graft rejection (1.5% versus 2.5%). CONCLUSIONS: This study shows that bone marrow should be the preferred stem cell source for matched sibling transplants in acquired aplastic anemia, in patients of all age groups. PMID- 22315498 TI - Cystatin C is associated with risk of venous thromboembolism in subjects with normal kidney function--the Tromso study. AB - BACKGROUND: Previous studies have shown an association between impaired kidney function, assessed by cystatin C-based estimated glomerular filtration rate, and venous thromboembolism. The aim of this study was to investigate whether serum cystatin C was associated with a risk of venous thromboembolism among subjects with normal kidney function in a prospective population-based study. DESIGN AND METHODS: Cystatin C was measured in serum from 3251 men and women with normal kidney function, aged 25-84 years, who participated in the Tromso study in 1994 1995. Normal kidney function was defined as a creatinine-based estimated glomerular filtration rate greater than 90 mL/min/1.73 m(2) and absence of microalbuminuria. Incident venous thromboembolism was registered from the date of inclusion through to the end of follow-up, September 1, 2007. Cox-regression models were used to calculate hazard ratios with 95% confidence intervals for venous thromboembolism. RESULTS: There were 83 incident venous thromboembolic events, of which 53 (63.9 %) were provoked, during a median of 12.3 years of follow-up. A one standard deviation (0.11 mg/L) increase in serum cystatin C levels was associated with a 43% (hazard ratio 1.43; 95% confidence interval 1.17 1.72) increased risk of total venous thromboembolism. Subjects with cystatin C levels in the top quartile (>= 0.87 mg/L) had a 2.5-fold (hazard ratio 2.51; 95% confidence interval 1.27-4.96) increased risk of venous thromboembolism compared to those with levels in the bottom quartile (<= 0.72 mg/L) in adjusted analysis. The risk estimates were even higher for provoked venous thromboembolism (hazard ratio 3.11; 95% confidence interval 1.23-7.86). CONCLUSIONS: Serum cystatin C levels were associated with the risk of venous thromboembolism in subjects with normal kidney function. Our findings suggest that elevated serum cystatin C levels may promote venous thrombosis beyond reflecting impaired kidney function. PMID- 22315499 TI - A novel, highly sensitive and rapid allele-specific loop-mediated amplification assay for the detection of the JAK2V617F mutation in chronic myeloproliferative neoplasms. AB - BACKGROUND: The identification of the JAK2V617F mutation is mandatory in the diagnostic work-up of Philadelphia chromosome-negative myeloproliferative neoplasms. Several molecular techniques to detect this mutation are currently available, but each of them has some limits. DESIGN AND METHODS: We set up a novel molecular method for the identification of the JAK2V617F mutation based on an allele-specific loop-mediated amplification, not polymerase chain reaction analysis. This innovative technique amplifies DNA targets under isothermal conditions with high specificity, efficiency and rapidity. The method does not require either a thermal cycler or gel separation and the DNA amplification reaction is visible to the naked eye and can be monitored by turbidimetry. This method was validated on DNA from cell lines as well as from patients with myeloproliferative neoplasms. The results were compared with those obtained by conventional polymerase chain reaction methods. RESULTS: This assay detects, within 1 hour, the JAK2V617F mutation down to an allele burden of 0.1-0.01%. All samples positive by polymerase chain reaction (n=146) proved positive when tested by allele-specific loop-mediated amplification and none of the 80 negative controls gave false positive results. In addition, six patients with essential thrombocythemia previously diagnosed as being JAK2V617F negative by polymerase chain reaction analysis were found to be positive (at a low level) by allele specific loop-mediated amplification. Furthermore, this assay discriminated the amount of JAK2V617F tumor allele within intervals of positivity, above 50%, between 50% and 10% and below 10%. CONCLUSIONS: Allele-specific loop-mediated amplification is a simple, robust and easily applicable method for the molecular diagnosis and monitoring of JAK2V617F mutation in patients with chronic myeloproliferative neoplasms. PMID- 22315500 TI - Hemoglobin sickle cell disease complications: a clinical study of 179 cases. AB - BACKGROUND: Hemoglobin sickle cell disease is one of the most frequent hemoglobinopathies. Surprisingly, few studies have been dedicated to this disease, currently considered to be a mild variant of homozygous sickle cell disease. The aim of this study was to update our knowledge about hemoglobin sickle cell disease. DESIGN AND METHODS: The study involved a single center series of 179 patients. Clinical and biological data were collected with special attention to the assessment of pulmonary arterial hypertension and nephropathy. RESULTS: Hemoglobin sickle cell diagnosis was delayed and performed in adulthood in 29% of cases. Prevalence of hospitalized painful vasoocclusive crisis, acute chest syndrome and priapism was 36%, 20% and 20%, respectively. The most common chronic organ complications were retinopathy and sensorineural otological disorders in 70% and 29% of cases. Indeed, prevalence of complications reported in homozygous sickle cell disease, such as nephropathy, suspicion of pulmonary hypertension, strokes and leg ulcers was rather low (13%, 4% and 1%, respectively). Phlebotomy performed in 36% of this population (baseline hemoglobin 11.5 g/dL) prevented recurrence of acute events in 71% of cases. CONCLUSIONS: Our data suggest that hemoglobin sickle cell disease should not be considered as a mild form of sickle cell anemia but as a separate disease with a special emphasis on viscosity-associated otological and ophthalmological disorders, and with a low prevalence of vasculopathy (strokes, pulmonary hypertension, ulcers and nephropathy). Phlebotomy was useful in reducing acute events and a wider use of this procedure should be further investigated. PMID- 22315501 TI - Myeloma cells contain high levels of inorganic polyphosphate which is associated with nucleolar transcription. AB - BACKGROUND: In hematology there has recently been increasing interest in inorganic polyphosphate. This polymer accumulates in platelet granules and its functions include modulating various stages of blood coagulation, inducing angiogenesis, and provoking apoptosis of plasma cells. In this study we evaluated the characteristics of intracellular polyphosphate in myeloma cell lines, in primary myeloma cells from patients, and in other human B-cell populations from healthy donors. DESIGN AND METHODS: We have developed a novel flow cytometric method for detecting levels of polyphosphate in cell populations. We also used confocal microscopy and enzymatic analysis to study polyphosphate localization and characteristics. RESULTS: We found that myeloma plasma cells contain higher levels of intracellular polyphosphate than normal plasma cells and other B-cell populations. Localization experiments indicated that high levels of polyphosphate accumulate in the nucleolus of myeloma cells. As the principal function of the nucleolus involves transcription of ribosomal DNA genes, we found changes in the cellular distribution of polyphosphate after the inhibition of nucleolar transcription. In addition, we found that RNA polymerase I activity, responsible for transcription in the nucleolus, is also modulated by polyphosphate, in a dose dependent manner. CONCLUSIONS: Our results show an unusually high accumulation of polyphosphate in the nucleoli of myeloma cells and a functional relationship of this polymer with nucleolar transcription. PMID- 22315502 TI - Genetic disruption of the PI3K regulatory subunits, p85alpha, p55alpha, and p50alpha, normalizes mutant PTPN11-induced hypersensitivity to GM-CSF. AB - Juvenile myelomonocytic leukemia is a lethal disease of children characterized by hypersensitivity of hematopoietic progenitors to granulocyte macrophage-colony stimulating factor. Mutations in PTPN11, the gene encoding the protein tyrosine phosphatase Shp2, are common in juvenile myelomonocytic leukemia and induce hyperactivation of the phosphoinositide-3-kinase pathway. We found that genetic disruption of Pik3r1, the gene encoding the Class IA phosphoinositide-3-kinase regulatory subunits p85alpha, p55alpha and p50alpha, significantly reduced hyperproliferation and hyperphosphorylation of Akt in gain-of-function Shp2 E76K expressing cells. Elevated protein levels of the phosphoinositide-3-kinase catalytic subunit, p110delta, in the Shp2 E76K-expressing Pik3r1-/- cells suggest that p110delta may be a crucial mediator of mutant Shp2-induced phosphoinositide 3-kinase hyperactivation. Consistently, treatment with the p110delta-specific inhibitor, IC87114, or the clinical grade pan-phosphoinositide-3-kinase inhibitor, GDC-0941, reduced granulocyte macrophage-colony stimulating factor hypersensitivity. Treatment with the farnesyltransferase inhibitor, tipifarnib, showed that Shp2 E76K induces hyperactivation of phosphoinositide-3-kinase by both Ras-dependent and Ras-independent mechanisms. Collectively, these findings implicate Class IA phosphoinositide-3-kinase as a relevant molecular target in juvenile myelomonocytic leukemia. PMID- 22315503 TI - Physical activity and BMI in a nationally representative sample of children and adolescents. AB - OBJECTIVE: To examine objectively measured physical activity levels by age, sex, and BMI for children and adolescents in a nationally representative sample. METHODS: Data were from the 2003-2004 and 2005-2006 National Health and Nutrition Examination Surveys, which included physical activity assessment by accelerometer and measured height and weight. The authors calculated minutes of moderate and vigorous activity. RESULTS: Boys were more active than girls, and activity levels were lower at older ages. Younger children met daily recommendations for physical activity, whereas older children, especially girls, did not. Typically, weight status was inversely related to activity, though differences were less apparent among boys. Underweight children were not always more active than heavier peers. PMID- 22315505 TI - Measuring quality improvement in public health: the development and psychometric testing of a QI Maturity Tool. AB - There is growing interest and investment in improving the quality of public health services and outcomes. Following the lead of other sectors, efforts are underway to introduce systematic quality improvement (QI) tools and approaches to state and local public health agencies. Little is known, however, about how to describe and reliably measure the level of QI maturity within a public health agency. The authors describe the development of a QI Maturity Tool using research from the fields of organizational design, psychology, health care, and complexity theory. The 37-item assessment tool is based on four quality domains derived from the literature: (a) organizational culture, (b) capacity and competency, (c) practice, and (d) alignment and spread. The tool was designed to identify features of an organization that may be enhancing or impeding QI; monitor the impact of efforts to create a more favorable environment for QI; and define potential cohorts of public health agencies for evaluation purposes. The article presents initial steps in testing and validating the QI Maturity Tool including: (a) developing a theoretical framework, (b) assuring face and content validity, (c) determining the tool's reliability based on estimates of internal consistency, (d) assessing the dimensionality, and (f) determining the construct validity of the instrument. The authors conclude that there is preliminary evidence that the QI Maturity Tool is a promising instrument. Further work is underway to explore whether self-reported survey results align with an agency's actions and the products of their QI efforts. PMID- 22315506 TI - A comparative in vitro study of the effects of separate and combined products of Citrus e fructibus and Cydonia e fructibus on immunological parameters of seasonal allergic rhinitis. AB - This paper examined the effects of the combined product, Citrus e fructibus/Cydonia e fructibus (Citrus/Cydonia; Citrus and Cydonia: each 0.01 g/mL), and separate products of Citrus (0.01 g/mL) and Cydonia (0.01 g/mL) on the immunological pathways involved in seasonal allergic rhinitis (SAR). Peripheral blood mononuclear cells (PBMCs) from five healthy and five grass pollen-allergic donors were isolated and analyzed in vitro after polyclonal and allergen-specific stimulation of T cells in the presence of the three extracts. The analyses demonstrated acceptable cell survival with no signs of toxicity. Citrus mainly had a selective effect on reducing allergen-specific chronic inflammatory (TNF alpha; Citrus compared to Cydonia and Citrus/Cydonia: -87.4 (P < 0.001) and -68.0 (P < 0.05), resp.) and Th2 pathway activity (IL-5; Citrus compared to Cydonia: 217.8 (P < 0.01); while, both Cydonia and Citrus/Cydonia mainly affected the induction of the allergen-specific Th1 pathway (IFN-gamma; Cydonia and Citrus/Cydonia compared to Citrus: 3.8 (P < 0.01) and 3.0 (P < 0.01), resp.). Citrus and Cydonia demonstrated different working mechanisms in the treatment of SAR and the combination product did not demonstrate larger effects than the separate preparations. Further effectiveness and efficacy studies comparing the effects of the products on SAR in vivo are indicated. PMID- 22315507 TI - Deoxyribonuclease is a potential counter regulator of aberrant neutrophil extracellular traps formation after major trauma. AB - INTRODUCTION: Neutrophil extracellular traps (NET) consist of a DNA scaffold that can be destroyed by Deoxyribonuclease (DNase). Thus DNases are potential prerequisites for natural counter regulation of NETs formation. In the present study, we determined the relationship of NETs and DNase after major trauma. METHODS: Thirty-nine major trauma patients, 14 with and 25 without sepsis development were enrolled in this prospective study. Levels of cell-free (cf) DNA/NETs and DNase were quantified daily from admission until day 9 after admission. RESULTS: Levels of cf-DNA/NETs in patients who developed sepsis were significantly increased after trauma. In the early septic phase, DNase values in septic patients were significantly increased compared to patients without sepsis (P < 0.05). cf-DNA/NETs values correlated to values of DNase in all trauma patients and patients with uneventful recovery (P < 0.01) but not in septic patients. Recombinant DNase efficiently degraded NETs released by stimulated neutrophils in a concentration-dependent manner in vitro. CONCLUSIONS: DNase degrades NETs in a concentration-dependent manner and therefore could have a potential regulatory effect on NET formation in neutrophils. This may inhibit the antibacterial effects of NETs or protect the tissue from autodestruction in inadequate NETs release in septic patients. PMID- 22315508 TI - Nanostructured, self-assembling peptide K5 blocks TNF-alpha and PGE2 production by suppression of the AP-1/p38 pathway. AB - Nanostructured, self-assembling peptides hold promise for a variety of regenerative medical applications such as 3D cell culture systems, accelerated wound healing, and nerve repair. The aim of this study was to determine whether the self-assembling peptide K5 can be applied as a carrier of anti-inflammatory drugs. First, we examined whether the K5 self-assembling peptide itself can modulate various cellular inflammatory responses. We found that peptide K5 significantly suppressed the release of tumor-necrosis-factor- (TNF-) alpha and prostaglandin E2 (PGE2) from RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS). Similarly, there was inhibition of cyclooxygenase- (COX-) 2 mRNA expression assessed by real-time PCR, indicating that the inhibition is at the transcriptional level. In agreement with this finding, peptide K5 suppressed the translocation of the transcription factors activator protein (AP-1) and c-Jun and inhibited upstream inflammatory effectors including mitogen activated protein kinase (MAPK), p38, and mitogen-activated protein kinase kinase 3/6 (MKK 3/6). Whether this peptide exerts its effects via a transmembrane or cytoplasmic receptor is not clear. However, our data strongly suggest that the nanostructured, self-assembling peptide K5 may possess significant anti-inflammatory activity via suppression of the p38/AP-1 pathway. PMID- 22315509 TI - Pegylated arginine deiminase downregulates colitis in murine models. AB - Arginine deiminase (ADI), an arginine-metabolizing enzyme involved in cell signaling, is dysregulated in multiple inflammatory diseases and cancers. We hypothesized that pegylated ADI (ADI-PEG) provide protection against colitis. METHODS: Dextran sodium sulfate colitis was induced in IL-10-deficient and BALB/c (WT) mice. ADI-PEG was administered i.p., and inflammatory mediators and pathology were evaluated. RESULTS: Acute colitis in mice was manifested by increases in inflammatory biomarkers, such as serum amyloid A (SAA, P < 0.001), IL-12 p40, and disease index (3-Fold). In contrast, ADI-PEG significantly decreased clinical disease index, SAA levels, and inflammatory cytokines in blood as well as in colonic explants. Animals developed moderate (2.2 +/- 0.3 WT) to severe (3.6 +/- 0.5 IL-10 deficient) colonic pathology; and ADI-PEG treatment significantly improved the severity of colitis (P < 0.05). Marked infiltration of CD68+ macrophages and iNOS expression were detected in colonic submucosa in colitic animals but not detected in ADI-PEG-treated animals. CONCLUSION: ADI-PEG attenuated inflammatory responses by suppression of macrophage infiltration and iNOS expression in colitic animals. ADI-PEG can serve as a potential therapeutic value in IBD. PMID- 22315510 TI - Serum IL-33 levels are associated with liver damage in patients with chronic hepatitis C. AB - Interleukin-33 (IL-33) is associated with the development of Th2 responses. This study examined the potential role of IL-33 in the pathogenic process of chronic hepatitis C (CHC) in Chinese patients. The levels of serum IL-33 and sST2 in 154 patients with CHC, 24 with spontaneously resolved HCV (SR-HCV) infection and 20 healthy controls (HC), were analyzed by ELISA. The concentrations of serum IL-2, IFN-gamma, TNF-alpha, IL-4, IL-6, and IL-10, HCV loads, ALT, AST, and HCV-Ab were measured. We found that the levels of serum IL-33 in CHC patients were significantly higher than those of SR-HCV and HC but decreased after treatment with interferon for 12 weeks. More importantly, the levels of serum IL-33 were correlated with the concentrations of ALT and AST in CHC patients. The levels of serum sST2, as a decoy receptor of IL-33, were significantly higher in CHC and SR CHC patients than those in HC, and there was no correlation between the levels of serum sST2 and IL-33. The concentrations of serum IFN-gamma and IL-6 in CHC patients were significantly lower than those of SR-HCV. These data suggest that IL-33 may be a pathogenic factor contributing to CHC-related liver injury. PMID- 22315511 TI - Proximity of residence to bodies of water and risk for west nile virus infection: a case-control study in Houston, Texas. AB - West Nile virus (WNV), a mosquito-borne virus, has clinically affected hundreds of residents in the Houston metropolitan area since its introduction in 2002. This study aimed to determine if living within close proximity to a water source increases one's odds of infection with WNV. We identified 356 eligible WNV positive cases and 356 controls using a population proportionate to size model with US Census Bureau data. We found that living near slow moving water sources was statistically associated with increased odds for human infection, while living near moderate moving water systems was associated with decreased odds for human infection. Living near bayous lined with vegetation as opposed to concrete also showed increased risk of infection. The habitats of slow moving and vegetation lined water sources appear to favor the mosquito-human transmission cycle. These methods can be used by resource-limited health entities to identify high-risk areas for arboviral disease surveillance and efficient mosquito management initiatives. PMID- 22315512 TI - Amniotic mesenchymal stem cells: a new source for hepatocyte-like cells and induction of CFTR expression by coculture with cystic fibrosis airway epithelial cells. AB - Cystic fibrosis (CF) is a monogenic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, with lung and liver manifestations. Because of pitfalls of gene therapy, novel approaches for reconstitution of the airway epithelium and CFTR expression should be explored. In the present study, human amniotic mesenchymal stem cells (hAMSCs) were isolated from term placentas and characterized for expression of phenotypic and pluripotency markers, and for differentiation potential towards mesoderm (osteogenic and adipogenic) lineages. Moreover, hAMSCs were induced to differentiate into hepatocyte-like cells, as demonstrated by mixed function oxidase activity and expression of albumin, alpha1-antitrypsin, and CK19. We also investigated the CFTR expression in hAMSCs upon isolation and in coculture with CF airway epithelial cells. Freshly isolated hAMSCs displayed low levels of CFTR mRNA, which even decreased with culture passages. Following staining with the vital dye CM-DiI, hAMSCs were mixed with CFBE41o- respiratory epithelial cells and seeded onto permeable filters. Flow cytometry demonstrated that 33-50% of hAMSCs acquired a detectable CFTR expression on the apical membrane, a result confirmed by confocal microscopy. Our data show that amniotic MSCs have the potential to differentiate into epithelial cells of organs relevant in CF pathogenesis and may contribute to partial correction of the CF phenotype. PMID- 22315513 TI - Plasmodium riboprotein PfP0 induces a deviant humoral immune response in Balb/c mice. AB - Passive immunization with antibodies to recombinant Plasmodium falciparum P0 riboprotein (rPfP0, 61-316 amino acids) provides protection against malaria. Carboxy-terminal 16 amino acids of the protein (PfP0C0) are conserved and show 69% identity to human and mouse P0. Antibodies to this domain are found in 10-15% of systemic lupus erythematosus patients. We probed the nature of humoral response to PfP0C0 by repeatedly immunizing mice with rPfP0. We failed to raise stable anti-PfP0C0 hybridomas from any of the 21 mice. The average serum anti PfP0C0 titer remained low (5.1 +/- 1.3 * 104). Pathological changes were observed in the mice after seven boosts. Adsorption with dinitrophenyl hapten revealed that the anti-PfP0C0 response was largely polyreactive. This polyreactivity was distributed across all isotypes. Similar polyreactive responses to PfP0 and PfP0C0 were observed in sera from malaria patients. Our data suggests that PfP0 induces a deviant humoral response, and this may contribute to immune evasion mechanisms of the parasite. PMID- 22315514 TI - Expression pattern of the alpha-kafirin promoter coupled with a signal peptide from Sorghum bicolor L. Moench. AB - Regulatory sequences with endosperm specificity are essential for foreign gene expression in the desired tissue for both grain quality improvement and molecular pharming. In this study, promoters of seed storage alpha-kafirin genes coupled with signal sequence (ss) were isolated from Sorghum bicolor L. Moench genomic DNA by PCR. The alpha-kafirin promoter (alpha-kaf) contains endosperm specificity determining motifs, prolamin-box, the O2-box 1, CATC, and TATA boxes required for alpha-kafirin gene expression in sorghum seeds. The constructs pMB-Ubi-gfp and pMB-kaf-gfp were microprojectile bombarded into various sorghum and sweet corn explants. GFP expression was detected on all explants using the Ubi promoter but only in seeds for the alpha-kaf promoter. This shows that the alpha-kaf promoter isolated was functional and demonstrated seed-specific GFP expression. The constructs pMB-Ubi-ss-gfp and pMB-kaf-ss-gfp were also bombarded into the same explants. Detection of GFP expression showed that the signal peptide (SP)::GFP fusion can assemble and fold properly, preserving the fluorescent properties of GFP. PMID- 22315515 TI - Copy-number variations observed in a Japanese population by BAC array CGH: summary of relatively rare CNVs. AB - Copy-number variations (CNVs) may contribute to genetic variation in humans. Reports regarding existence and characteristics of CNVs in a large apparently healthy Japanese cohort are quite limited. We report the data from a screening of 213 unrelated Japanese individuals using comparative genomic hybridization based on a bacterial artificial chromosome microarray (BAC aCGH). In a previous paper, we summarized the data by focusing on highly polymorphic CNVs (in >= 5.0 % of the individuals). However, rare variations have recently received attention from scientists who espouse a hypothesis called "common disease and rare variants." Here, we report CNVs identified in fewer than 10 individuals in our study population. We found a total of 126 CNVs at 52 different BAC regions in the genome. The CNVs observed at 27 of the 52 BAC-regions were found in only one unrelated individual. The majority of CNVs found in this study were not identified in the Japanese who were examined in the other studies. Family studies were conducted, and the results demonstrated that the CNVs were inherited from one parent in the families. PMID- 22315516 TI - Modulation of tight junction structure and function by kinases and phosphatases targeting occludin. AB - Tight junctions (TJs) typically represent the most apical contacts in epithelial and endothelial cell layers where they play an essential role in the separation of extracellular or luminal spaces from underlying tissues in the body. Depending on the protein composition, TJs define the barrier characteristics and in addition maintain cell polarity. Two major families of integral membrane proteins form the typical TJ strand network, the tight junction-associated MARVEL protein (TAMP) family members occludin, tricellulin, and MarvelD3 as well as a specific set of claudins. Occludin was the first identified member of these tetraspanins and is now widely accepted as a regulator of TJ assembly and function. Therefore, occludin itself has to be tightly regulated. Phosphorylation of occludin appears to be of central importance in this context. Here we want to summarize current knowledge on the kinases and phosphatases directly modifying occludin, and their role in the regulation of TJ structure, function, and dynamics. PMID- 22315517 TI - Undertreatment of COPD: a retrospective analysis of US managed care and Medicare patients. AB - BACKGROUND: We investigated a large population of patients with chronic obstructive pulmonary disease (COPD) to determine their frequency of medication use and patterns of pharmacotherapy. METHODS: Medical and pharmacy claims data were retrospectively analyzed from 19 health plans (>7.79 million members) across the US. Eligible patients were aged >=40 years, continuously enrolled during July 2004 to June 2005, and had at least one inpatient or at least two outpatient claims coded for COPD. As a surrogate for severity of illness, COPD patients were stratified by complexity of illness using predefined International Classification of Diseases, Ninth Revision, Clinical Modification, Current Procedural Terminology, Fourth Edition, and Healthcare Common Procedure Coding System codes. RESULTS: A total of 42,565 patients with commercial insurance and 8507 Medicare patients were identified. Their mean age was 54.7 years and 74.8 years, and 48.7% and 46.9% were male, respectively. In total, 66.3% of commercial patients (n = 28,206) were not prescribed any maintenance COPD pharmacotherapy (59.1% no medication; 7.2% inhaled short-acting beta2-agonist only). In the Medicare population, 70.9% (n = 6031) were not prescribed any maintenance COPD pharmacotherapy (66.0% no medication; 4.9% short-acting beta2-agonist only). A subset of patients classified as high-complexity were similarly undertreated, with 58.7% (5358/9121) of commercial and 68.8% (1616/2350) of Medicare patients not prescribed maintenance COPD pharmacotherapy. Only 18.0% and 9.8% of diagnosed smokers in the commercial and Medicare cohorts had a claim for a smoking cessation intervention and just 16.6% and 23.5%, respectively, had claims for an influenza vaccination. CONCLUSION: This study highlights a high degree of undertreatment of COPD in both commercial and Medicare patients, with most patients receiving no maintenance pharmacotherapy or influenza vaccination. PMID- 22315518 TI - Clinical and economic outcomes for patients initiating fluticasone propionate/salmeterol combination therapy (250/50 mcg) versus anticholinergics in a comorbid COPD/depression population. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is frequently associated with comorbid depression and anxiety. Managing COPD symptoms and exacerbations through use of appropriate and adequate pharmacotherapy in this population may result in better COPD-related outcomes. METHODS: This retrospective, observational study used administrative claims of patients aged 40 years and older with COPD and comorbid depression/anxiety identified from January 1, 2004 through June 30, 2008. Patients were assigned to fluticasone propionate/salmeterol 250/50 mcg combination (FSC) or anticholinergics (AC) based on their first (index) prescription. The risks of COPD exacerbations and healthcare utilization and costs were compared between cohorts during 1 year of follow-up. RESULTS: The adjusted risk of a COPD-related exacerbation during the 1 year follow-up period was 30% higher in the AC cohort (n = 2923) relative to the FSC cohort (n = 1078) (odds ratio [OR]: 1.30, 95% confidence interval [CI]: 1.08 1.56) after controlling for baseline differences in covariates. The risks of COPD related hospitalizations and emergency department visits were 56% and 65% higher, respectively, in the AC cohort compared with the FSC cohort. The average number of COPD-related hospitalizations during the follow-up period was 46% higher for the AC cohort compared with the FSC cohort (incidence rate ratio [IRR]: 1.46, 95% CI: 1.01-2.09, P = 0.041). The savings from lower COPD-related medical costs ($692 vs $1042, P < 0.050) kept the COPD-related total costs during the follow-up period comparable to those in the AC cohort ($1659 vs $1677, P > 0.050) although the pharmacy costs were higher in the FSC cohort. CONCLUSIONS: FSC compared with AC was associated with more favorable COPD-related outcomes and lower COPD related utilization and medical costs among patients with COPD and comorbid anxiety/depression. PMID- 22315519 TI - Bronchoscopic thermal vapor ablation in a canine model of emphysema. AB - Clinical studies indicate the potential of bronchoscopic thermal vapor ablation to result in clinically relevant improvements in severe chronic obstructive pulmonary disease patients with upper lobe-predominant emphysema. However, the mechanisms by which vapor ablation results in lung volume reduction are not fully known. This study determined the 3-month safety and efficacy of vapor ablation in a canine model of emphysema and described the histopathological changes in the lung. The cranial lobes of papain-exposed dogs were treated with a vapor dose of ten calories per gram of lung tissue (n = 8) or were sham treated (n = 3). Safety was monitored peri- and postoperatively for 3 months. Animals were then sacrificed, estimates of lung volume reduction performed, and the lungs processed for histology. Vapor ablation was associated with an average of 20% volume reduction of the treated lobes and an absence of serious adverse events. The amount of lobar volume reduction was correlated with the amount of fibrosis and atelectasis in the treated lobe. Bronchoscopic thermal vapor ablation at a dose of 10 cal/g results in lobar volume reduction associated with remodeling of the targeted tissue characterized by mature collagen formation in the absence of major adverse events. PMID- 22315520 TI - Optimizing management of chronic obstructive pulmonary disease in the upcoming decade. PMID- 22315521 TI - Municipality screening of citizens with suspicion of chronic obstructive pulmonary disease. AB - Up to 436,000 adult Danes suffer from chronic obstructive pulmonary disease (COPD), with only one third diagnosed at this time. The Danish National Board of Health recommends early detection of COPD, focusing on smokers/ex-smokers over 35 years of age with at least one lung symptom. A governmental prevention committee has suggested that the municipalities, in addition to general practice, should be a potential arena responsible for early detection of COPD. We undertook a pilot study to investigate the feasibility and effectiveness of early detection of COPD in municipalities following the recommendations of the Danish National Board of Health. METHODS: The Municipality of Esbjerg offered spirometry to Danish citizens at risk of COPD without a previous diagnosis of the disease, following the National Board of Health's recommendations. Citizens with evidence of airway obstruction (forced expiratory volume in one second [FEV(1)]/forced vital capacity [FVC] <70%) were advised to visit their general practitioner for diagnosis. These citizens were followed up by telephone interview 3 months later. RESULTS: Of 152 citizens sampled (50% females, mean age 58 years, 51% smokers) 51.3% had evidence of airway obstruction, with 87% being mild to moderate in terms of severity. Seven of ten citizens (71%) then visited their general practitioner, with 85% of these being diagnosed with COPD. The number of smokers embarking on smoking cessation or quitting smoking increased following COPD screening, with the highest frequency in participants with evidence of airway obstruction. CONCLUSION: In addition to early detection of COPD in general practice, early detection of airway obstruction in defined risk populations in Danish municipalities seems feasible and effective for identifying new patients with COPD. However, additional research is needed in larger samples to confirm the results of the present study. PMID- 22315522 TI - STAT3 Regulates Proliferation and Immunogenicity of the Ewing Family of Tumors In Vitro. AB - The Ewing sarcoma family of tumors (ESFT) represents an aggressive spectrum of malignant tumour types with common defining histological and cytogenetic features. To evaluate the functional activation of signal transducer and activator of transcription 3 (STAT3) in ESFT, we evaluated its activation in primary tissue sections and observed the functional consequences of its inhibition in ESFT cell lines. STAT3 was activated (tyrosine 705-phosphorylated) in 18 out of 31 primary tumours (58%), either diffusely (35%) or focally (23%). STAT3 was constitutively activated in 3 out of 3 ESFT cell lines tested, and its specific chemical inhibition resulted in complete loss of cell viability. STAT3 inhibition in ESFT cell lines was associated with several consistent changes in chemokine profile suggesting a role of STAT3 in ESFT in both cell survival and modification of the cellular immune environment. Together these data support the investigation of STAT3 inhibitors for the Ewing family of tumors. PMID- 22315523 TI - An efficient pipeline wavefront phase recovery for the CAFADIS camera for extremely large telescopes. AB - In this paper we show a fast, specialized hardware implementation of the wavefront phase recovery algorithm using the CAFADIS camera. The CAFADIS camera is a new plenoptic sensor patented by the Universidad de La Laguna (Canary Islands, Spain): international patent PCT/ES2007/000046 (WIPO publication number WO/2007/082975). It can simultaneously measure the wavefront phase and the distance to the light source in a real-time process. The pipeline algorithm is implemented using Field Programmable Gate Arrays (FPGA). These devices present architecture capable of handling the sensor output stream using a massively parallel approach and they are efficient enough to resolve several Adaptive Optics (AO) problems in Extremely Large Telescopes (ELTs) in terms of processing time requirements. The FPGA implementation of the wavefront phase recovery algorithm using the CAFADIS camera is based on the very fast computation of two dimensional fast Fourier Transforms (FFTs). Thus we have carried out a comparison between our very novel FPGA 2D-FFTa and other implementations. PMID- 22315524 TI - Toward 100 Mega-frames per second: design of an ultimate ultra-high-speed image sensor. AB - Our experience in the design of an ultra-high speed image sensor targeting the theoretical maximum frame rate is summarized. The imager is the backside illuminated in situ storage image sensor (BSI ISIS). It is confirmed that the critical factor limiting the highest frame rate is the signal electron transit time from the generation layer at the back side of each pixel to the input gate to the in situ storage area on the front side. The theoretical maximum frame rate is estimated at 100 Mega-frames per second (Mfps) by transient simulation study. The sensor has a spatial resolution of 140,800 pixels with 126 linear storage elements installed in each pixel. The very high sensitivity is ensured by application of backside illumination technology and cooling. The ultra-high frame rate is achieved by the in situ storage image sensor (ISIS) structure on the front side. In this paper, we summarize technologies developed to achieve the theoretical maximum frame rate, including: (1) a special p-well design by triple injections to generate a smooth electric field backside towards the collection gate on the front side, resulting in much shorter electron transit time; (2) design technique to reduce RC delay by employing an extra metal layer exclusively to electrodes responsible for ultra-high speed image capturing; (3) a CCD specific complementary on-chip inductance minimization technique with a couple of stacked differential bus lines. PMID- 22315525 TI - Electronic nose for quality control of Colombian coffee through the detection of defects in "Cup Tests". AB - Electronic noses (ENs), are used for many applications, but we must emphasize the importance of their application to foodstuffs like coffee. This paper presents a research study about the analysis of Colombian coffee samples for the detection and classification of defects (i.e., using "Cup Tests"), which was conducted at the Almacafe quality control laboratory in Cucuta, Colombia. The results obtained show that the application of an electronic nose called "A-NOSE", may be used in the coffee industry for the cupping tests. The results show that e-nose technology can be a useful tool for quality control to evaluate the excellence of the Colombian coffee produced by National Federation of Coffee Growers. PMID- 22315526 TI - A focusing method in the calibration process of image sensors based on IOFBs. AB - A focusing procedure in the calibration process of image sensors based on Incoherent Optical Fiber Bundles (IOFBs) is described using the information extracted from fibers. These procedures differ from any other currently known focusing method due to the non spatial in-out correspondence between fibers, which produces a natural codification of the image to transmit. Focus measuring is essential prior to carrying out calibration in order to guarantee accurate processing and decoding. Four algorithms have been developed to estimate the focus measure; two methods based on mean grey level, and the other two based on variance. In this paper, a few simple focus measures are defined and compared. Some experimental results referred to the focus measure and the accuracy of the developed methods are discussed in order to demonstrate its effectiveness. PMID- 22315527 TI - ISFET based microsensors for environmental monitoring. AB - The use of microsensors for in-field monitoring of environmental parameters is gaining interest due to their advantages over conventional sensors. Among them microsensors based on semiconductor technology offer additional advantages such as small size, robustness, low output impedance and rapid response. Besides, the technology used allows integration of circuitry and multiple sensors in the same substrate and accordingly they can be implemented in compact probes for particular applications e.g., in situ monitoring and/or on-line measurements. In the field of microsensors for environmental applications, Ion Selective Field Effect Transistors (ISFETs) have a special interest. They are particularly helpful for measuring pH and other ions in small volumes and they can be integrated in compact flow cells for continuous measurements. In this paper the technologies used to fabricate ISFETs and a review of the role of ISFETs in the environmental field are presented. PMID- 22315528 TI - RAC-multi: reader anti-collision algorithm for multichannel mobile RFID networks. AB - At present, RFID is installed on mobile devices such as mobile phones or PDAs and provides a means to obtain information about objects equipped with an RFID tag over a multi-channeled telecommunication networks. To use mobile RFIDs, reader collision problems should be addressed given that readers are continuously moving. Moreover, in a multichannel environment for mobile RFIDs, interference between adjacent channels should be considered. This work first defines a new concept of a reader collision problem between adjacent channels and then suggests a novel reader anti-collision algorithm for RFID readers that use multiple channels. To avoid interference with adjacent channels, the suggested algorithm separates data channels into odd and even numbered channels and allocates odd numbered channels first to readers. It also sets an unused channel between the control channel and data channels to ensure that control messages and the signal of the adjacent channel experience no interference. Experimental results show that suggested algorithm shows throughput improvements ranging from 29% to 46% for tag identifications compared to the GENTLE reader anti-collision algorithm for multichannel RFID networks. PMID- 22315529 TI - The inflammasome in host defense. AB - Nod-like receptors have emerged as an important family of sensors in host defense. These receptors are expressed in macrophages, dendritic cells and monocytes and play an important role in microbial immunity. Some Nod-like receptors form the inflammasome, a protein complex that activates caspase-1 in response to several stimuli. Caspase-1 activation leads to processing and secretion of pro-inflammatory cytokines such as interleukin (IL)-1beta and IL-18. Here, we discuss recent advances in the inflammasome field with an emphasis on host defense. We also compare differential requirements for inflammasome activation in dendritic cells, macrophages and monocytes. PMID- 22315530 TI - Tracking control of shape-memory-alloy actuators based on self-sensing feedback and inverse hysteresis compensation. AB - Shape memory alloys (SMAs) offer a high power-to-weight ratio, large recovery strain, and low driving voltages, and have thus attracted considerable research attention. The difficulty of controlling SMA actuators arises from their highly nonlinear hysteresis and temperature dependence. This paper describes a combination of self-sensing and model-based control, where the model includes both the major and minor hysteresis loops as well as the thermodynamics effects. The self-sensing algorithm uses only the power width modulation (PWM) signal and requires no heavy equipment. The method can achieve high-accuracy servo control and is especially suitable for miniaturized applications. PMID- 22315531 TI - A study of MAC protocols for WBANs. AB - The seamless integration of low-power, miniaturised, invasive/non-invasive lightweight sensor nodes have contributed to the development of a proactive and unobtrusive Wireless Body Area Network (WBAN). A WBAN provides long-term health monitoring of a patient without any constraint on his/her normal dailylife activities. This monitoring requires the low-power operation of invasive/non invasive sensor nodes. In other words, a power-efficient Medium Access Control (MAC) protocol is required to satisfy the stringent WBAN requirements, including low-power consumption. In this paper, we first outline the WBAN requirements that are important for the design of a low-power MAC protocol. Then we study low-power MAC protocols proposed/investigated for a WBAN with emphasis on their strengths and weaknesses. We also review different power-efficient mechanisms for a WBAN. In addition, useful suggestions are given to help the MAC designers to develop a low-power MAC protocol that will satisfy the stringent requirements. PMID- 22315532 TI - Chip-oriented fluorimeter design and detection system development for DNA quantification in nano-liter volumes. AB - The chip-based polymerase chain reaction (PCR) system has been developed in recent years to achieve DNA quantification. Using a microstructure and miniature chip, the volume consumption for a PCR can be reduced to a nano-liter. With high speed cycling and a low reaction volume, the time consumption of one PCR cycle performed on a chip can be reduced. However, most of the presented prototypes employ commercial fluorimeters which are not optimized for fluorescence detection of such a small quantity sample. This limits the performance of DNA quantification, especially low experiment reproducibility. This study discusses the concept of a chip-oriented fluorimeter design. Using the analytical model, the current study analyzes the sensitivity and dynamic range of the fluorimeter to fit the requirements for detecting fluorescence in nano-liter volumes. Through the optimized processes, a real-time PCR on a chip system with only one nano liter volume test sample is as sensitive as the commercial real-time PCR machine using the sample with twenty micro-liter volumes. The signal to noise (S/N) ratio of a chip system for DNA quantification with hepatitis B virus (HBV) plasmid samples is 3 dB higher. DNA quantification by the miniature chip shows higher reproducibility compared to the commercial machine with respect to samples of initial concentrations from 10(3) to 10(5) copies per reaction. PMID- 22315533 TI - Microfabrication of microchannels for fuel cell plates. AB - Portable electronic devices such as notebook computers, PDAs, cellular phones, etc., are being widely used, and they increasingly need cheap, efficient, and lightweight power sources. Fuel cells have been proposed as possible power sources to address issues that involve energy production and the environment. In particular, a small type of fuel-cell system is known to be suitable for portable electronic devices. The development of micro fuel cell systems can be achieved by the application of microchannel technology. In this study, the conventional method of chemical etching and the mechanical machining method of micro end milling were used for the microfabrication of microchannel for fuel cell separators. The two methods were compared in terms of their performance in the fabrication with regards to dimensional errors, flatness, straightness, and surface roughness. Following microchannel fabrication, the powder blasting technique is introduced to improve the coating performance of the catalyst on the surface of the microchannel. Experimental results show that end milling can remarkably increase the fabrication performance and that surface treatment by powder blasting can improve the performance of catalyst coating. PMID- 22315534 TI - Recent advances in sensing oropharyngeal swallowing function in Japan. AB - Dysphagia (difficulty in swallowing) is an important issue in the elderly because it causes aspiration pneumonia, which is the second largest cause of death in this group. It also causes decline in activities of daily living and quality of life. The oral phase of swallowing has been neglected, despite its importance in the evaluation of dysphagia, because adequate protocols and measuring devices are unavailable. However, recent advances in sensor technology have enabled straightforward, non-invasive measurement of the movement of important swallowing related organs such as the lips and tongue, as well as the larynx. In this article, we report the present state and possibility of clinical application of such systems developed in Japan. PMID- 22315535 TI - 1-Hydroxypyrene--a biochemical marker for PAH pollution assessment of aquatic ecosystem. AB - The aim of the present study was to assess aquatic contamination by polycyclic aromatic hydrocarbons (PAH), using the 1-hydroxypyrene (1-OHP) content in fish bile as a biochemical marker. A total of 71 chub (Leuciscus cephalus L.) were collected from seven locations on the Svitava and Svratka rivers in and around the industrial city of Brno, Czech Republic. The levels of 1-OHP were determined by reverse phase HPLC with fluorescence detection after deconjugation. Normalising the molar concentration of the biliary 1-OHP to the biliary protein content reduced sample variation. The content of 1-OHP was correlated with the PAH level in bottom sediment and semi-permeable membrane devices (SPMD), which was analyzed by a combination of HPLC/FLD and GC/MS methods. The highest mean values of 1-OHP were found in fish caught at the Svratka River at locations Modrice (169.2 +/- 99.7 ng . mg(-1) protein) and Rajhradice (152.2 +/- 79.7 ng . mg(-1) protein), which are located downstream from Brno. These values were significantly (P < 0.05) higher than those obtained from localities Kninicky (98.4 +/- 66.1 ng . mg(-1) protein) and Bilovice nad Svitavou (64.1 +/- 31.4 ng . mg(-1) protein). The lowest contents of PAH in sediment and SPMD were found at location Kninicky (1.5 mg . kg(-1) dry mass and 19.4 ng . L(-1), respectively). The highest contents of PAH in sediment and SPMD were found in Rajhradice (26.0 mg . kg(-1) dry mass) and Svitava before junction (65.4 ng . L(-1)), respectively. A Spearman correlation test was applied to determine the relationship between biliary 1-OHP and the sum of PAH in sediment and SPMD. A positive, but no statistically significant correlation was found. The main impact sources of elevated level of PAHs in sites located downstream from Brno are most probably intensive industrial and agricultural activities and domestic waste. PMID- 22315536 TI - Design, control and in situ visualization of gas nitriding processes. AB - The article presents a complex system of design, in situ visualization and control of the commonly used surface treatment process: the gas nitriding process. In the computer design conception, analytical mathematical models and artificial intelligence methods were used. As a result, possibilities were obtained of the poly-optimization and poly-parametric simulations of the course of the process combined with a visualization of the value changes of the process parameters in the function of time, as well as possibilities to predict the properties of nitrided layers. For in situ visualization of the growth of the nitrided layer, computer procedures were developed which make use of the results of the correlations of direct and differential voltage and time runs of the process result sensor (magnetic sensor), with the proper layer growth stage. Computer procedures make it possible to combine, in the duration of the process, the registered voltage and time runs with the models of the process. PMID- 22315537 TI - A multi-fault diagnosis method for sensor systems based on principle component analysis. AB - A model based on PCA (principal component analysis) and a neural network is proposed for the multi-fault diagnosis of sensor systems. Firstly, predicted values of sensors are computed by using historical data measured under fault-free conditions and a PCA model. Secondly, the squared prediction error (SPE) of the sensor system is calculated. A fault can then be detected when the SPE suddenly increases. If more than one sensor in the system is out of order, after combining different sensors and reconstructing the signals of combined sensors, the SPE is calculated to locate the faulty sensors. Finally, the feasibility and effectiveness of the proposed method is demonstrated by simulation and comparison studies, in which two sensors in the system are out of order at the same time. PMID- 22315538 TI - Spectroscopic and chromatographic characterization of wastewater organic matter from a biological treatment plant. AB - Spectroscopic and chromatographic changes in dissolved organic matter (DOM) characteristics of influent and treated sewage were investigated for a wastewater treatment plant (WWTP) with a biological advanced process. Refractory DOM (R-DOM) was defined as the dissolved organic carbon concentrations of the samples after 28-day incubation for this study. Specific UV absorbance (SUVA), hydrophobicity, synchronous fluorescence spectra and molecular weight (MW) distributions were selected as DOM characteristics. The percent distribution of R-DOM for the effluent was much higher than that of the influent, indicating that biodegradable DOM was selectively removed during the process. Comparison of the influent versus the effluent sewage revealed that SUVA, fulvic-like fluorescence (FLF), humic like fluorescence (HLF), the apparent MW values were enhanced during the treatment. This suggests that more aromatic and humic-like compounds were enriched during the biological process. No significant difference in the DOM characteristics was observed between the original effluent (i.e., prior to the incubation) and the influent sewage after the incubation. This result suggests that the major changes in wastewater DOM characteristics occurring during the biological advanced process were similar to those for simple microbial incubation. PMID- 22315539 TI - Field map reconstruction in magnetic resonance imaging using Bayesian estimation. AB - Field inhomogeneities in Magnetic Resonance Imaging (MRI) can cause blur or image distortion as they produce off-resonance frequency at each voxel. These effects can be corrected if an accurate field map is available. Field maps can be estimated starting from the phase of multiple complex MRI data sets. In this paper we present a technique based on statistical estimation in order to reconstruct a field map exploiting two or more scans. The proposed approach implements a Bayesian estimator in conjunction with the Graph Cuts optimization method. The effectiveness of the method has been proven on simulated and real data. PMID- 22315540 TI - A novel biosensor for evaluation of apoptotic or necrotic effects of nitrogen dioxide during acute pancreatitis in rat. AB - The direct and accurate estimation of nitric dioxide levels is an extremely laborious and technically demanding procedure in the molecular diagnostics of inflammatory processes. The aim of this work is to demonstrate that a stop-flow technique utilizing a specific spectroscopic biosensor can be used for detection of nanomolar quantities of NO(2) in biological milieu. The use of novel compound cis-[Cr(C(2)O(4))(AaraNH(2))(OH(2))(2)](+) increases NO(2) estimation accuracy by slowing down the rate of NO(2) uptake. In this study, an animal model of pancreatitis, where nitrosative stress is induced by either 3g/kg bw or 1.5 g/kg bw dose of L-arginine, was used. Biochemical parameters and morphological characteristics of acute pancreatitis were monitored, specifically assessing pancreatic acinar cell death mode, NO(2) generation and cellular glutathione level. The severity of the process correlated positively with NO(2) levels in pancreatic acinar cell cytosol samples, and negatively with cellular glutathione levels. PMID- 22315541 TI - PIYAS-proceeding to intelligent service oriented memory allocation for flash based data centric sensor devices in wireless sensor networks. AB - Flash memory has become a more widespread storage medium for modern wireless devices because of its effective characteristics like non-volatility, small size, light weight, fast access speed, shock resistance, high reliability and low power consumption. Sensor nodes are highly resource constrained in terms of limited processing speed, runtime memory, persistent storage, communication bandwidth and finite energy. Therefore, for wireless sensor networks supporting sense, store, merge and send schemes, an efficient and reliable file system is highly required with consideration of sensor node constraints. In this paper, we propose a novel log structured external NAND flash memory based file system, called Proceeding to Intelligent service oriented memorY Allocation for flash based data centric Sensor devices in wireless sensor networks (PIYAS). This is the extended version of our previously proposed PIYA [1]. The main goals of the PIYAS scheme are to achieve instant mounting and reduced SRAM space by keeping memory mapping information to a very low size of and to provide high query response throughput by allocation of memory to the sensor data by network business rules. The scheme intelligently samples and stores the raw data and provides high in-network data availability by keeping the aggregate data for a longer period of time than any other scheme has done before. We propose effective garbage collection and wear leveling schemes as well. The experimental results show that PIYAS is an optimized memory management scheme allowing high performance for wireless sensor networks. PMID- 22315542 TI - Improving the response of accelerometers for automotive applications by using LMS adaptive filters. AB - In this paper, the least-mean-squares (LMS) algorithm was used to eliminate noise corrupting the important information coming from a piezoresisitive accelerometer for automotive applications. This kind of accelerometer is designed to be easily mounted in hard to reach places on vehicles under test, and they usually feature ranges from 50 to 2,000 g (where is the gravitational acceleration, 9.81 m/s(2)) and frequency responses to 3,000 Hz or higher, with DC response, durable cables, reliable performance and relatively low cost. However, here we show that the response of the sensor under test had a lot of noise and we carried out the signal processing stage by using both conventional and optimal adaptive filtering. Usually, designers have to build their specific analog and digital signal processing circuits, and this fact increases considerably the cost of the entire sensor system and the results are not always satisfactory, because the relevant signal is sometimes buried in a broad-band noise background where the unwanted information and the relevant signal sometimes share a very similar frequency band. Thus, in order to deal with this problem, here we used the LMS adaptive filtering algorithm and compare it with others based on the kind of filters that are typically used for automotive applications. The experimental results are satisfactory. PMID- 22315543 TI - An evolution based biosensor receptor DNA sequence generation algorithm. AB - A biosensor is composed of a bioreceptor, an associated recognition molecule, and a signal transducer that can selectively detect target substances for analysis. DNA based biosensors utilize receptor molecules that allow hybridization with the target analyte. However, most DNA biosensor research uses oligonucleotides as the target analytes and does not address the potential problems of real samples. The identification of recognition molecules suitable for real target analyte samples is an important step towards further development of DNA biosensors. This study examines the characteristics of DNA used as bioreceptors and proposes a hybrid evolution-based DNA sequence generating algorithm, based on DNA computing, to identify suitable DNA bioreceptor recognition molecules for stable hybridization with real target substances. The Traveling Salesman Problem (TSP) approach is applied in the proposed algorithm to evaluate the safety and fitness of the generated DNA sequences. This approach improves efficiency and stability for enhanced and variable-length DNA sequence generation and allows extension to generation of variable-length DNA sequences with diverse receptor recognition requirements. PMID- 22315544 TI - Infiltration route analysis using thermal observation devices (TOD) and optimization techniques in a GIS environment. AB - Infiltration-route analysis is a military application of geospatial information system (GIS) technology. In order to find susceptible routes, optimal-path searching algorithms are applied to minimize the cost function, which is the summed result of detection probability. The cost function was determined according to the thermal observation device (TOD) detection probability, the viewshed analysis results, and two feature layers extracted from the vector product interim terrain data. The detection probability is computed and recorded for an individual cell (50 m * 50 m), and the optimal infiltration routes are determined with A* algorithm by minimizing the summed costs on the routes from a start point to an end point. In the present study, in order to simulate the dynamic nature of a real-world problem, one thousand cost surfaces in the GIS environment were generated with randomly located TODs and randomly selected infiltration start points. Accordingly, one thousand sets of vulnerable routes for infiltration purposes could be found, which could be accumulated and presented as an infiltration vulnerability map. This application can be further utilized for both optimal infiltration routing and surveillance network design. Indeed, dynamic simulation in the GIS environment is considered to be a powerful and practical solution for optimization problems. A similar approach can be applied to the dynamic optimal routing for civil infrastructure, which requires consideration of terrain-related constraints and cost functions. PMID- 22315545 TI - Binary fingerprints at fluctuation-enhanced sensing. AB - We have developed a simple way to generate binary patterns based on spectral slopes in different frequency ranges at fluctuation-enhanced sensing. Such patterns can be considered as binary "fingerprints" of odors. The method has experimentally been demonstrated with a commercial semiconducting metal oxide (Taguchi) sensor exposed to bacterial odors (Escherichia coli and Anthrax surrogate Bacillus subtilis) and processing their stochastic signals. With a single Taguchi sensor, the situations of empty chamber, tryptic soy agar (TSA) medium, or TSA with bacteria could be distinguished with 100% reproducibility. The bacterium numbers were in the range of 2.5 * 10(4)-10(6). To illustrate the relevance for ultra-low power consumption, we show that this new type of signal processing and pattern recognition task can be implemented by a simple analog circuitry and a few logic gates with total power consumption in the microWatts range. PMID- 22315546 TI - Building intelligent communication systems for handicapped aphasiacs. AB - This paper presents an intelligent system allowing handicapped aphasiacs to perform basic communication tasks. It has the following three key features: (1) A 6-sensor data glove measures the finger gestures of a patient in terms of the bending degrees of his fingers. (2) A finger language recognition subsystem recognizes language components from the finger gestures. It employs multiple regression analysis to automatically extract proper finger features so that the recognition model can be fast and correctly constructed by a radial basis function neural network. (3) A coordinate-indexed virtual keyboard allows the users to directly access the letters on the keyboard at a practical speed. The system serves as a viable tool for natural and affordable communication for handicapped aphasiacs through continuous finger language input. PMID- 22315547 TI - Characterization, modeling and design parameters identification of silicon carbide junction field effect transistor for temperature sensor applications. AB - Sensor technology is moving towards wide-band-gap semiconductors providing high temperature capable devices. Indeed, the higher thermal conductivity of silicon carbide, (three times more than silicon), permits better heat dissipation and allows better cooling and temperature management. Though many temperature sensors have already been published, little endeavours have been invested in the study of silicon carbide junction field effect devices (SiC-JFET) as a temperature sensor. SiC-JFETs devices are now mature enough and it is close to be commercialized. The use of its specific properties versus temperatures is the major focus of this paper. The SiC-JFETs output current-voltage characteristics are characterized at different temperatures. The saturation current and its on-resistance versus temperature are successfully extracted. It is demonstrated that these parameters are proportional to the absolute temperature. A physics-based model is also presented. Relationships between on-resistance and saturation current versus temperature are introduced. A comparative study between experimental data and simulation results is conducted. Important to note, the proposed model and the experimental results reflect a successful agreement as far as a temperature sensor is concerned. PMID- 22315548 TI - Collaborative localization in wireless sensor networks via pattern recognition in radio irregularity using omnidirectional antennas. AB - In recent years, various received signal strength (RSS)-based localization estimation approaches for wireless sensor networks (WSNs) have been proposed. RSS based localization is regarded as a low-cost solution for many location-aware applications in WSNs. In previous studies, the radiation patterns of all sensor nodes are assumed to be spherical, which is an oversimplification of the radio propagation model in practical applications. In this study, we present an RSS based cooperative localization method that estimates unknown coordinates of sensor nodes in a network. Arrangement of two external low-cost omnidirectional dipole antennas is developed by using the distance-power gradient model. A modified robust regression is also proposed to determine the relative azimuth and distance between a sensor node and a fixed reference node. In addition, a cooperative localization scheme that incorporates estimations from multiple fixed reference nodes is presented to improve the accuracy of the localization. The proposed method is tested via computer-based analysis and field test. Experimental results demonstrate that the proposed low-cost method is a useful solution for localizing sensor nodes in unknown or changing environments. PMID- 22315549 TI - Nanotechnology for early cancer detection. AB - Vast numbers of studies and developments in the nanotechnology area have been conducted and many nanomaterials have been utilized to detect cancers at early stages. Nanomaterials have unique physical, optical and electrical properties that have proven to be very useful in sensing. Quantum dots, gold nanoparticles, magnetic nanoparticles, carbon nanotubes, gold nanowires and many other materials have been developed over the years, alongside the discovery of a wide range of biomarkers to lower the detection limit of cancer biomarkers. Proteins, antibody fragments, DNA fragments, and RNA fragments are the base of cancer biomarkers and have been used as targets in cancer detection and monitoring. It is highly anticipated that in the near future, we might be able to detect cancer at a very early stage, providing a much higher chance of treatment. PMID- 22315550 TI - Reliability testing procedure for MEMS IMUs applied to vibrating environments. AB - The diffusion of micro electro-mechanical systems (MEMS) technology applied to navigation systems is rapidly increasing, but currently, there is a lack of knowledge about the reliability of this typology of devices, representing a serious limitation to their use in aerospace vehicles and other fields with medium and high requirements. In this paper, a reliability testing procedure for inertial sensors and inertial measurement units (IMU) based on MEMS for applications in vibrating environments is presented. The sensing performances were evaluated in terms of signal accuracy, systematic errors, and accidental errors; the actual working conditions were simulated by means of an accelerated dynamic excitation. A commercial MEMS-based IMU was analyzed to validate the proposed procedure. The main weaknesses of the system have been localized by providing important information about the relationship between the reliability levels of the system and individual components. PMID- 22315551 TI - Ultramicroelectrode array based sensors: a promising analytical tool for environmental monitoring. AB - The particular analytical performance of ultramicroelectrode arrays (UMEAs) has attracted a high interest by the research community and has led to the development of a variety of electroanalytical applications. UMEA-based approaches have demonstrated to be powerful, simple, rapid and cost-effective analytical tools for environmental analysis compared to available conventional electrodes and standardised analytical techniques. An overview of the fabrication processes of UMEAs, their characterization and applications carried out by the Spanish scientific community is presented. A brief explanation of theoretical aspects that highlight their electrochemical behavior is also given. Finally, the applications of this transducer platform in the environmental field are discussed. PMID- 22315552 TI - Optimal clinical time for reliable measurement of transcutaneous CO2 with ear probes: counterbalancing overshoot and the vasodilatation effect. AB - OBJECTIVES: To determine the optimal clinical reading time for the transcutaneous measurement of oxygen saturation (SpO(2)) and transcutaneous CO(2) (TcPCO(2)) in awake spontaneously breathing individuals, considering the overshoot phenomenon (transient overestimation of arterial PaCO(2)). EXPERIMENTAL SECTION: Observational study of 91 (75 men) individuals undergoing forced spirometry, measurement of SpO(2) and TcPCO(2) with the SenTec monitor every two minutes until minute 20 and arterial blood gas (ABG) analysis. Overshoot severity: (a) mild (0.1-1.9 mm Hg); (b) moderate (2-4.9 mm Hg); (c) severe: (>5 mm Hg). The mean difference was calculated for SpO(2) and TcPCO(2) and arterial values of PaCO(2) and SpO(2). The intraclass correlation coefficient (ICC) between monitor readings and blood values was calculated as a measure of agreement. RESULTS: The mean age was 63.1 +/- 11.8 years. Spirometric values: FVC: 75.4 +/- 6.2%; FEV(1): 72.9 +/- 23.9%; FEV(1)/FVC: 70 +/- 15.5%. ABG: PaO(2): 82.6 +/- 13.2; PaCO(2): 39.9.1 +/- 4.8 mmHg; SaO(2): 95.3 +/- 4.4%. Overshoot analysis: overshoot was mild in 33 (36.3%) patients, moderate in 20 (22%) and severe in nine (10%); no overshoot was observed in 29 (31%) patients. The lowest mean differences between arterial blood gas and TcPCO(2) was -0.57 mmHg at minute 10, although the highest ICC was obtained at minutes 12 and 14 (>0.8). The overshoot lost its influence after minute 12. For SpO(2), measurements were reliable at minute 2. CONCLUSIONS: The optimal clinical reading measurement recommended for the ear lobe TcPCO(2) measurement ranges between minute 12 and 14. The SpO(2) measurement can be performed at minute 2. PMID- 22315553 TI - SBMAC: smart blocking MAC mechanism for variable UW-ASN (Underwater Acoustic Sensor Network) environment. AB - In this paper, several MAC scheduling methods applicable to an underwater environment are proposed. Besides, a new marine communication system model was proposed to improve the reliability of the proposed SBMAC method. The scheme minimizes transmission of control frames except for data transmission and various transmission methods and ACK methods can be used together. Simulation models are set indices and analysis of the underwater environment is established to conduct reliable simulations. Consequently, the performance improvement of the proposed method is verified with respect to delay time, data transmission rate, memory utilization, energy efficiency, etc. PMID- 22315554 TI - Nano-bio-technology and sensing chips: new systems for detection in personalized therapies and cell biology. AB - Further advances in molecular medicine and cell biology also require new electrochemical systems to detect disease biomarkers and therapeutic compounds. Microelectronic technology offers powerful circuits and systems to develop innovative and miniaturized biochips for sensing at the molecular level. However, microelectronic biochips proposed in the literature often do not show the right specificity, sensitivity, and reliability required by biomedical applications. Nanotechnology offers new materials and solutions to improve the surface properties of sensing probes. The aim of the present paper is to review the most recent progress in Nano-Bio-Technology in the area of the development of new electrochemical systems for molecular detection in personalized therapy and cell culture monitoring. PMID- 22315555 TI - Semiconductor laser multi-spectral sensing and imaging. AB - Multi-spectral laser imaging is a technique that can offer a combination of the laser capability of accurate spectral sensing with the desirable features of passive multispectral imaging. The technique can be used for detection, discrimination, and identification of objects by their spectral signature. This article describes and reviews the development and evaluation of semiconductor multi-spectral laser imaging systems. Although the method is certainly not specific to any laser technology, the use of semiconductor lasers is significant with respect to practicality and affordability. More relevantly, semiconductor lasers have their own characteristics; they offer excellent wavelength diversity but usually with modest power. Thus, system design and engineering issues are analyzed for approaches and trade-offs that can make the best use of semiconductor laser capabilities in multispectral imaging. A few systems were developed and the technique was tested and evaluated on a variety of natural and man-made objects. It was shown capable of high spectral resolution imaging which, unlike non-imaging point sensing, allows detecting and discriminating objects of interest even without a priori spectroscopic knowledge of the targets. Examples include material and chemical discrimination. It was also shown capable of dealing with the complexity of interpreting diffuse scattered spectral images and produced results that could otherwise be ambiguous with conventional imaging. Examples with glucose and spectral imaging of drug pills were discussed. Lastly, the technique was shown with conventional laser spectroscopy such as wavelength modulation spectroscopy to image a gas (CO). These results suggest the versatility and power of multi-spectral laser imaging, which can be practical with the use of semiconductor lasers. PMID- 22315556 TI - ELBARA II, an L-band radiometer system for soil moisture research. AB - L-band (1-2 GHz) microwave radiometry is a remote sensing technique that can be used to monitor soil moisture, and is deployed in the Soil Moisture and Ocean Salinity (SMOS) Mission of the European Space Agency (ESA). Performing ground based radiometer campaigns before launch, during the commissioning phase and during the operative SMOS mission is important for validating the satellite data and for the further improvement of the radiative transfer models used in the soil moisture retrieval algorithms. To address these needs, three identical L-band radiometer systems were ordered by ESA. They rely on the proven architecture of the ETH L-Band radiometer for soil moisture research (ELBARA) with major improvements in the microwave electronics, the internal calibration sources, the data acquisition, the user interface, and the mechanics. The purpose of this paper is to describe the design of the instruments and the main characteristics that are relevant for the user. PMID- 22315557 TI - Formation of zwitterionic fullerodendron using a new DBN-focal dendron. AB - A new poly(amidoamine) dendron having 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) at the focal point was synthesized. Interestingly, formation of zwitterionic fullerodendrons (lambda(max) = 930 nm for C(60) and 795 nm for C(70)) were observed by Vis-NIR spectroscopy upon the reaction of C(60) or C(70) with the DBN focal dendron. In particular, the C(70) anion was effectively stabilized by the site isolation effect of the dendritic wedge. The half-life of fullerodendron 12b having C(70) anion at the focal point reaches 7,345 min, which is 20 times longer than that of complex between C(60) and pristine DBN. Furthermore, in order to confirm the structure of the zwitterionic complex, fullerodendron 12a was reprecipitated from benzonitrile/1,2,4-trimethylbenzene, and was observed using IR spectroscopy and APPI-MS. PMID- 22315558 TI - A disposable organophosphorus pesticides enzyme biosensor based on magnetic composite nano-particles modified screen printed carbon electrode. AB - A disposable organophosphorus pesticides (OPs) enzyme biosensor based on magnetic composite nanoparticle-modified screen printed carbon electrodes (SPCE) has been developed. Firstly, an acetylcholinesterase (AChE)-coated Fe(3)O(4)/Au (GMP) magnetic nanoparticulate (GMP-AChE) was synthesized. Then, GMP-AChE was absorbed on the surface of a SPCE modified by carbon nanotubes (CNTs)/nano-ZrO(2)/prussian blue (PB)/Nafion (Nf) composite membrane by an external magnetic field. Thus, the biosensor (SPCE?CNTs/ZrO(2)/PB/Nf?GMP-AChE) for OPs was fabricated. The surface of the biosensor was characterized by scanning electron micrography (SEM) and X ray fluorescence spectrometery (XRFS) and its electrochemical properties were studied by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The degree of inhibition (A%) of the AChE by OPs was determined by measuring the reduction current of the PB generated by the AChE-catalyzed hydrolysis of acetylthiocholine (ATCh). In pH = 7.5 KNO(3) solution, the A was related linearly to the concentration of dimethoate in the range from 1.0 * 10(-3)-10 ng . mL(-1) with a detection limit of 5.6 * 10(-4) ng . mL(-1). The recovery rates in Chinese cabbage exhibited a range of 88%-105%. The results were consistent with the standard gas chromatography (GC) method. Compared with other enzyme biosensors the proposed biosensor exhibited high sensitivity, good selectivity with disposable, low consumption of sample. In particular its surface can be easily renewed by removal of the magnet. The convenient, fast and sensitive voltammetric measurement opens new opportunities for OPs analysis. PMID- 22315559 TI - An innovative procedure for calibration of strapdown electro-optical sensors onboard unmanned air vehicles. AB - This paper presents an innovative method for estimating the attitude of airborne electro-optical cameras with respect to the onboard autonomous navigation unit. The procedure is based on the use of attitude measurements under static conditions taken by an inertial unit and carrier-phase differential Global Positioning System to obtain accurate camera position estimates in the aircraft body reference frame, while image analysis allows line-of-sight unit vectors in the camera based reference frame to be computed. The method has been applied to the alignment of the visible and infrared cameras installed onboard the experimental aircraft of the Italian Aerospace Research Center and adopted for in flight obstacle detection and collision avoidance. Results show an angular uncertainty on the order of 0.1 degrees (rms). PMID- 22315560 TI - Label-free toxin detection by means of time-resolved electrochemical impedance spectroscopy. AB - The real-time detection of trace concentrations of biological toxins requires significant improvement of the detection methods from those reported in the literature. To develop a highly sensitive and selective detection device it is necessary to determine the optimal measuring conditions for the electrochemical sensor in three domains: time, frequency and polarization potential. In this work we utilized a time-resolved electrochemical impedance spectroscopy for the detection of trace concentrations of Staphylococcus enterotoxin B (SEB). An anti SEB antibody has been attached to the nano-porous aluminum surface using 3 aminopropyltriethoxysilane/glutaraldehyde coupling system. This immobilization method allows fabrication of a highly reproducible and stable sensing device. Using developed immobilization procedure and optimized detection regime, it is possible to determine the presence of SEB at the levels as low as 10 pg/mL in 15 minutes. PMID- 22315561 TI - A macroporous TiO2 oxygen sensor fabricated using anodic aluminium oxide as an etching mask. AB - An innovative fabrication method to produce a macroporous Si surface by employing an anodic aluminium oxide (AAO) nanopore array layer as an etching template is presented. Combining AAO with a reactive ion etching (RIE) processes, a homogeneous and macroporous silicon surface can be effectively configured by modulating AAO process parameters and alumina film thickness, thus hopefully replacing conventional photolithography and electrochemical etch methods. The hybrid process integration is considered fully CMOS compatible thanks to the low temperature AAO and CMOS processes. The gas-sensing characteristics of 50 nm TiO(2) nanofilms deposited on the macroporous surface are compared with those of conventional plain (or non-porous) nanofilms to verify reduced response noise and improved sensitivity as a result of their macroporosity. Our experimental results reveal that macroporous geometry of the TiO(2) chemoresistive gas sensor demonstrates 2-fold higher (~33%) improved sensitivity than a non-porous sensor at different levels of oxygen exposure. In addition, the macroporous device exhibits excellent discrimination capability and significantly lessened response noise at 500 degrees C. Experimental results indicate that the hybrid process of such miniature and macroporous devices are compatible as well as applicable to integrated next generation bio-chemical sensors. PMID- 22315562 TI - Fast Fourier transform IR characterization of epoxy GY systems crosslinked with aliphatic and cycloaliphatic EH polyamine adducts. AB - The use of fast FT-IR spectroscopy as a sensitive method to estimate a change of the crosslinking kinetics of epoxy resin with polyamine adducts is described in this study. A new epoxy formulation based on the use of polyamine adducts as the hardeners was analyzed. Crosslinking reactions of the different stoichiometric mixtures of the unmodified GY250 epoxy resin with the aliphatic EH606 and the cycloaliphatic EH637 polyamine adducts were studied using mid FT-IR spectroscopic techniques. As the crosslinking proceeded, the primary amine groups in polyamine adduct are converted to secondary and the tertiary amines. The decrease in the IR band intensity of epoxy groups at about 915 cm(-1), as well as at about 3,056 cm( 1), was observed due to process. Mid IR spectral analysis was used to calculate the content of the epoxy groups as a function of crosslinking time and the crosslinking degree of resin. The amount of all the epoxy species was estimated from IR spectra to changes during the crosslinking kinetics of epichlorhydrin. PMID- 22315563 TI - Real-time PCR machine system modeling and a systematic approach for the robust design of a real-time PCR-on-a-chip system. AB - Chip-based DNA quantification systems are widespread, and used in many point-of care applications. However, instruments for such applications may not be maintained or calibrated regularly. Since machine reliability is a key issue for normal operation, this study presents a system model of the real-time Polymerase Chain Reaction (PCR) machine to analyze the instrument design through numerical experiments. Based on model analysis, a systematic approach was developed to lower the variation of DNA quantification and achieve a robust design for a real time PCR-on-a-chip system. Accelerated lift testing was adopted to evaluate the reliability of the chip prototype. According to the life test plan, this proposed real-time PCR-on-a-chip system was simulated to work continuously for over three years with similar reproducibility in DNA quantification. This not only shows the robustness of the lab-on-a-chip system, but also verifies the effectiveness of our systematic method for achieving a robust design. PMID- 22315564 TI - Deflection of cross-ply composite laminates induced by piezoelectric actuators. AB - The coupling effects between the mechanical and electric properties of piezoelectric materials have drawn significant attention for their potential applications as sensors and actuators. In this investigation, two piezoelectric actuators are symmetrically surface bonded on a cross-ply composite laminate. Electric voltages with the same amplitude and opposite sign are applied to the two symmetric piezoelectric actuators, resulting in the bending effect on the laminated plate. The bending moment is derived by using the classical laminate theory and piezoelectricity. The analytical solution of the flexural displacement of the simply supported composite plate subjected to the bending moment is solved by using the plate theory. The analytical solution is compared with the finite element solution to show the validation of present approach. The effects of the size and location of the piezoelectric actuators on the response of the composite laminate are presented through a parametric study. A simple model incorporating the classical laminate theory and plate theory is presented to predict the deformed shape of the simply supported laminate plate. PMID- 22315565 TI - Evaluation of oil-palm fungal disease infestation with canopy hyperspectral reflectance data. AB - Fungal disease detection in perennial crops is a major issue in estate management and production. However, nowadays such diagnostics are long and difficult when only made from visual symptom observation, and very expensive and damaging when based on root or stem tissue chemical analysis. As an alternative, we propose in this study to evaluate the potential of hyperspectral reflectance data to help detecting the disease efficiently without destruction of tissues. This study focuses on the calibration of a statistical model of discrimination between several stages of Ganoderma attack on oil palm trees, based on field hyperspectral measurements at tree scale. Field protocol and measurements are first described. Then, combinations of pre-processing, partial least square regression and linear discriminant analysis are tested on about hundred samples to prove the efficiency of canopy reflectance in providing information about the plant sanitary status. A robust algorithm is thus derived, allowing classifying oil-palm in a 4-level typology, based on disease severity from healthy to critically sick stages, with a global performance close to 94%. Moreover, this model discriminates sick from healthy trees with a confidence level of almost 98%. Applications and further improvements of this experiment are finally discussed. PMID- 22315566 TI - Development of an alcohol dehydrogenase biosensor for ethanol determination with toluidine blue O covalently attached to a cellulose acetate modified electrode. AB - In this work, a novel voltammetric ethanol biosensor was constructed using alcohol dehydrogenase (ADH). Firstly, alcohol dehydrogenase was immobilized on the surface of a glassy carbon electrode modified by cellulose acetate (CA) bonded to toluidine blue O (TBO). Secondly, the surface was covered by a glutaraldehyde/bovine serum albumin (BSA) cross-linking procedure to provide a new voltammetric sensor for the ethanol determination. In order to fabricate the biosensor, a new electrode matrix containing insoluble Toluidine Blue O (TBO) was obtained from the process, and enzyme/coenzyme was combined on the biosensor surface. The influence of various experimental conditions was examined for the characterization of the optimum analytical performance. The developed biosensor exhibited sensitive and selective determination of ethanol and showed a linear response between 1 * 10(-5) M and 4 * 10(-4) M ethanol. A detection limit calculated as three times the signal-to-noise ratio was 5.0 * 10(-6) M. At the end of the 20(th) day, the biosensor still retained 50% of its initial activity. PMID- 22315567 TI - A nanopore structured high performance toluene gas sensor made by nanoimprinting method. AB - Toluene gas was successfully measured at room temperature using a device microfabricated by a nanoimprinting method. A highly uniform nanoporous thin film was produced with a dense array of titania (TiO(2)) pores with a diameter of 70 ~ 80 nm using this method. This thin film had a Pd/TiO(2) nanoporous/SiO(2)/Si MIS layered structure with Pd-TiO(2) as the catalytic sensing layer. The nanoimprinting method was useful in expanding the TiO(2) surface area by about 30%, as confirmed using AFM and SEM imaging. The measured toluene concentrations ranged from 50 ppm to 200 ppm. The toluene was easily detected by changing the Pd/TiO(2) interface work function, resulting in a change in the I-V characteristics. PMID- 22315568 TI - Statistical modeling of SAR images: a survey. AB - Statistical modeling is essential to SAR (Synthetic Aperture Radar) image interpretation. It aims to describe SAR images through statistical methods and reveal the characteristics of these images. Moreover, statistical modeling can provide a technical support for a comprehensive understanding of terrain scattering mechanism, which helps to develop algorithms for effective image interpretation and creditable image simulation. Numerous statistical models have been developed to describe SAR image data, and the purpose of this paper is to categorize and evaluate these models. We first summarize the development history and the current researching state of statistical modeling, then different SAR image models developed from the product model are mainly discussed in detail. Relevant issues are also discussed. Several promising directions for future research are concluded at last. PMID- 22315569 TI - The non-linear relationship between muscle voluntary activation level and voluntary force measured by the interpolated twitch technique. AB - Interpolated twitch technique (ITT) is a non-invasive method for assessing the completeness of muscle activation in clinical settings. Voluntary activation level (VA), measured by ITT and estimated by a conventional linear model, was reported to have a non-linear relationship with true voluntary contraction force at higher activation levels. The relationship needs to be further clarified for the correct use by clinicians and researchers. This study was to established a modified voluntary activation (modified VA) and define a valid range by fitting a non-linear logistic growth model. Eight healthy male adults participated in this study. Each subject performed three sets of voluntary isometric ankle plantar flexions at 20, 40, 60, 80 and 100% maximal voluntary contraction (MVC) with real time feedback on a computer screen. A supramaximal electrical stimulation was applied on tibia nerve at rest and during contractions. The estimated VA was calculated for each contraction. The relationship between the estimated VA and the actual voluntary contraction force was fitted by a logistic growth model. The result showed that according to the upper and lower limit points of the logistic curve, the valid range was between the 95.16% and 10.55% MVC. The modified VA estimated by this logistic growth model demonstrated less error than the conventional model. This study provided a transfer function for the voluntary activation level and defined the valid range which would provide useful information in clinical applications. PMID- 22315570 TI - Effective route maintenance and restoration schemes in mobile ad hoc networks. AB - This study proposes a location-based hybrid routing protocol to improve data packet delivery and to reduce control message overhead in mobile ad hoc networks. In mobile environments, where nodes move continuously at a high speed, it is generally difficult to maintain and restore route paths. Therefore, this study suggests a new flooding mechanism to control route paths. The essence of the proposed scheme is its effective tracking of the destination's location based on the beacon messages of the main route nodes. Through experiments based on an NS-2 simulator, the proposed scheme shows improvements in the data packet delivery ratio and reduces the amount of routing control message overhead compared with existing routing protocols such as AODV, LAR, ZRP and AODV-DFR. PMID- 22315571 TI - Intelligent sensors security. AB - The paper is focused on the security issues of sensors provided with processors and software and used for high-risk applications. Common IT related threats may cause serious consequences for sensor system users. To improve their robustness, sensor systems should be developed in a restricted way that would provide them with assurance. One assurance creation methodology is Common Criteria (ISO/IEC 15408) used for IT products and systems. The paper begins with a primer on the Common Criteria, and then a general security model of the intelligent sensor as an IT product is discussed. The paper presents how the security problem of the intelligent sensor is defined and solved. The contribution of the paper is to provide Common Criteria (CC) related security design patterns and to improve the effectiveness of the sensor development process. PMID- 22315572 TI - Vision-based traffic data collection sensor for automotive applications. AB - This paper presents a complete vision sensor onboard a moving vehicle which collects the traffic data in its local area in daytime conditions. The sensor comprises a rear looking and a forward looking camera. Thus, a representative description of the traffic conditions in the local area of the host vehicle can be computed. The proposed sensor detects the number of vehicles (traffic load), their relative positions and their relative velocities in a four-stage process: lane detection, candidates selection, vehicles classification and tracking. Absolute velocities (average road speed) and global positioning are obtained after combining the outputs provided by the vision sensor with the data supplied by the CAN Bus and a GPS sensor. The presented experiments are promising in terms of detection performance and accuracy in order to be validated for applications in the context of the automotive industry. PMID- 22315573 TI - Fluorescence-based sensing of 2,4,6-trinitrotoluene (TNT) using a multi-channeled poly(methyl methacrylate) (PMMA) microimmunosensor. AB - Fluorescence immunoassays employing monoclonal antibodies directed against the explosive 2,4,6-trinitrotoluene (TNT) were conducted in a multi-channel microimmunosensor. The multi-channel microimmunosensor was prepared in poly (methyl methacrylate) (PMMA) via hot embossing from a brass molding tool. The multi-channeled microfluidic device was sol-gel coated to generate a siloxane surface that provided a scaffold for antibody immobilization. AlexaFluor cadaverine-trinitrobenzene (AlexaFluor-Cad-TNB) was used as the reporter molecule in a displacement immunoassay. The limit of detection was 1-10 ng/mL (ppb) with a linear dynamic range that covered three orders of magnitude. In addition, antibody crossreactivity was investigated using hexahydro-1,3,5-triazine (RDX), HMX, 2,4-dinitrotoluene (DNT), 4-nitrotoluene (4-NT) and 2-amino-4,6-DNT. PMID- 22315574 TI - Pterins as sensors of response to the application of Fe3+ -dextran in piglets. AB - The aim of the presented study was to assess the effect of a single administration of Fe(3+)-dextran on immune cell counts and pterin biomolecule production as novel sensors of the piglets' immune system activation, and to determine concentrations of cortisol, a traditional hormonal biosensor of the stress response. Pterins (neopterin and biopterin) in the piglets' blood serum were analyzed by separation using reversed-phase HPLC. A single dose of Fe(3+) dextran produced a special stress situation in the piglets' organism which manifested itself by an increased production of neopterin (p < 0.05) and biopterin (p < 0.01) in the experimental piglets. Changes in cortisol concentrations and leukocyte counts were influenced by handling stress and were not specifically correlated to iron dextran application. Iron concentrations in the internal environment of the experimental piglets' group were higher by an order of magnitude compared with the controls, and the highest serum concentrations of iron (p < 0.01) were reached 24 h following Fe(3+)-dextran administration. The data presented offer a new perspective on the evaluation of stress situations in the animal organism and, not least importantly, extends the rather modest current list of references on the role of pterins in livestock animals. PMID- 22315575 TI - Microencapsulation of flavors in carnauba wax. AB - The subject of this study is the development of flavor wax formulations aimed for food and feed products. The melt dispersion technique was applied for the encapsulation of ethyl vanillin in wax microcapsules. The surface morphology of microparticles was investigated using scanning electron microscope (SEM), while the loading content was determined by HPLC measurements. This study shows that the decomposition process under heating proceeds in several steps: vanilla evaporation occurs at around 200 degrees C, while matrix degradation starts at 250 degrees C and progresses with maxima at around 360, 440 and 520 degrees C. The results indicate that carnauba wax is an attractive material for use as a matrix for encapsulation of flavours in order to improve their functionality and stability in products. PMID- 22315576 TI - Analysis of large scale spatial variability of soil moisture using a geostatistical method. AB - Spatial and temporal soil moisture dynamics are critically needed to improve the parameterization for hydrological and meteorological modeling processes. This study evaluates the statistical spatial structure of large-scale observed and simulated estimates of soil moisture under pre- and post-precipitation event conditions. This large scale variability is a crucial in calibration and validation of large-scale satellite based data assimilation systems. Spatial analysis using geostatistical approaches was used to validate modeled soil moisture by the Agriculture Meteorological (AGRMET) model using in situ measurements of soil moisture from a state-wide environmental monitoring network (Oklahoma Mesonet). The results show that AGRMET data produces larger spatial decorrelation compared to in situ based soil moisture data. The precipitation storms drive the soil moisture spatial structures at large scale, found smaller decorrelation length after precipitation. This study also evaluates the geostatistical approach for mitigation for quality control issues within in situ soil moisture network to estimates at soil moisture at unsampled stations. PMID- 22315578 TI - A device for automatically measuring and supervising the critical care patient's urine output. AB - Critical care units are equipped with commercial monitoring devices capable of sensing patients' physiological parameters and supervising the achievement of the established therapeutic goals. This avoids human errors in this task and considerably decreases the workload of the healthcare staff. However, at present there still is a very relevant physiological parameter that is measured and supervised manually by the critical care units' healthcare staff: urine output. This paper presents a patent-pending device capable of automatically recording and supervising the urine output of a critical care patient. A high precision scale is used to measure the weight of a commercial urine meter. On the scale's pan there is a support frame made up of Bosch profiles that isolates the scale from force transmission from the patient's bed, and guarantees that the urine flows properly through the urine meter input tube. The scale's readings are sent to a PC via Bluetooth where an application supervises the achievement of the therapeutic goals. The device is currently undergoing tests at a research unit associated with the University Hospital of Getafe in Spain. PMID- 22315579 TI - Improving the response of accelerometers for automotive applications by using LMS adaptive filters: Part II. AB - In this paper, the fast least-mean-squares (LMS) algorithm was used to both eliminate noise corrupting the important information coming from a piezoresisitive accelerometer for automotive applications, and improve the convergence rate of the filtering process based on the conventional LMS algorithm. The response of the accelerometer under test was corrupted by process and measurement noise, and the signal processing stage was carried out by using both conventional filtering, which was already shown in a previous paper, and optimal adaptive filtering. The adaptive filtering process relied on the LMS adaptive filtering family, which has shown to have very good convergence and robustness properties, and here a comparative analysis between the results of the application of the conventional LMS algorithm and the fast LMS algorithm to solve a real-life filtering problem was carried out. In short, in this paper the piezoresistive accelerometer was tested for a multi-frequency acceleration excitation. Due to the kind of test conducted in this paper, the use of conventional filtering was discarded and the choice of one adaptive filter over the other was based on the signal-to-noise ratio improvement and the convergence rate. PMID- 22315580 TI - Nanomaterials as analytical tools for genosensors. AB - Nanomaterials are being increasingly used for the development of electrochemical DNA biosensors, due to the unique electrocatalytic properties found in nanoscale materials. They offer excellent prospects for interfacing biological recognition events with electronic signal transduction and for designing a new generation of bioelectronic devices exhibiting novel functions. In particular, nanomaterials such as noble metal nanoparticles (Au, Pt), carbon nanotubes (CNTs), magnetic nanoparticles, quantum dots and metal oxide nanoparticles have been actively investigated for their applications in DNA biosensors, which have become a new interdisciplinary frontier between biological detection and material science. In this article, we address some of the main advances in this field over the past few years, discussing the issues and challenges with the aim of stimulating a broader interest in developing nanomaterial-based biosensors and improving their applications in disease diagnosis and food safety examination. PMID- 22315581 TI - A novel bioinspired PVDF micro/nano hair receptor for a robot sensing system. AB - This paper describes the concept and design of a novel artificial hair receptor for the sensing system of micro intelligent robots such as a cricket-like jumping mini robot. The concept is inspired from the natural hair receptor of animals, also called cilium or filiform hair by different research groups, which is usually used as a vibration receptor or a flow detector by insects, mammals and fishes. The suspended fiber model is firstly built and the influence of scaling down is analyzed theoretically. The design of this artificial hair receptor is based on aligned suspended PVDF (polyvinylidene fluoride) fibers, manufactures with a novel method called thermo-direct drawing technique, and aligned suspended submicron diameter fibers are thus successfully fabricated on a flexible Kapton. In the post process step, some key problems such as separated electrodes deposition along with the fiber drawing direction and poling of micro/nano fibers to impart them with good piezoeffective activity have been presented. The preliminary validation experiments show that the artificial hair receptor has a reliable response with good sensibility to external pressure variation and, medium flow as well as its prospects in the application on sensing system of mini/micro bio-robots. PMID- 22315582 TI - Dapoxetine: an evidence-based review of its effectiveness in treatment of premature ejaculation. AB - Premature ejaculation (PE) is a major issue in male sexual health. The global prevalence of PE is estimated to be between 20% and 40%, making it the most common sexual dysfunction in men. PE causes distress and reduced quality of life for patients and has a negative impact on interpersonal relationships. Historically, it has been treated with cognitive therapy, behavioral methods, and off-label use of selective serotonin reuptake inhibitors usually used to treat depression and other psychological disorders. Dapoxetine is a selective serotonin reuptake inhibitor specifically designed to treat PE. This paper reviews the current evidence for use of dapoxetine in the treatment of PE in adult men. There is substantial evidence that dapoxetine 30 mg or 60 mg taken "on-demand" results in a significant increase in intravaginal ejaculatory latency time when compared with placebo. Patient-reported outcomes are clearly improved relative to placebo following dapoxetine therapy, indicating greater control over ejaculation, more satisfaction with intercourse, less ejaculation-related distress, and, importantly, significantly reduced interpersonal difficulty. These data were supported by consistent reports of improvement in Clinical Global Impression of change in PE following treatment with dapoxetine. Further studies are needed to evaluate long-term efficacy and health economics. The unique pharmacology of dapoxetine makes it ideal for on-demand dosing, and the clinical evidence shows dapoxetine to be an efficacious and tolerable treatment for lifelong and acquired PE. PMID- 22315583 TI - 3D Rigid Registration of Intraoperative Ultrasound and Preoperative MR Brain Images Based on Hyperechogenic Structures. AB - The registration of intraoperative ultrasound (US) images with preoperative magnetic resonance (MR) images is a challenging problem due to the difference of information contained in each image modality. To overcome this difficulty, we introduce a new probabilistic function based on the matching of cerebral hyperechogenic structures. In brain imaging, these structures are the liquid interfaces such as the cerebral falx and the sulci, and the lesions when the corresponding tissue is hyperechogenic. The registration procedure is achieved by maximizing the joint probability for a voxel to be included in hyperechogenic structures in both modalities. Experiments were carried out on real datasets acquired during neurosurgical procedures. The proposed validation framework is based on (i) visual assessment, (ii) manual expert estimations , and (iii) a robustness study. Results show that the proposed method (i) is visually efficient, (ii) produces no statistically different registration accuracy compared to manual-based expert registration, and (iii) converges robustly. Finally, the computation time required by our method is compatible with intraoperative use. PMID- 22315584 TI - Selective Extraction of Entangled Textures via Adaptive PDE Transform. AB - Texture and feature extraction is an important research area with a wide range of applications in science and technology. Selective extraction of entangled textures is a challenging task due to spatial entanglement, orientation mixing, and high-frequency overlapping. The partial differential equation (PDE) transform is an efficient method for functional mode decomposition. The present work introduces adaptive PDE transform algorithm to appropriately threshold the statistical variance of the local variation of functional modes. The proposed adaptive PDE transform is applied to the selective extraction of entangled textures. Successful separations of human face, clothes, background, natural landscape, text, forest, camouflaged sniper and neuron skeletons have validated the proposed method. PMID- 22315585 TI - PPARs in Regulation of Paraoxonases: Control of Oxidative Stress and Inflammation Pathways. AB - The paraoxonase (PON) group of enzymes, composed of PON1, PON2, and PON3, play an important role in decreasing oxidative stress by degrading lipid peroxides. PON1 synthesis is upregulated by PPAR. Several pharmacological compounds (acting as antioxidants and, hence, atheroprotective) stimulate both PPAR activity and PON1 expression. Recent evidence suggests that PON1 and the monocyte chemoattractant protein-1 (MCP-1) are involved in coordinating the inflammatory response in damaged tissues; PPAR may be central in the regulation of these biochemical pathways. This article reviews the state of knowledge on PON1 biochemistry and function, the influence of genetic variation, and the regulation of PON1 expression by pharmaceutical compounds that increase PPAR activity. We also describe recent lines of evidence suggesting links between PON1 and MCP-1 and how their production may be regulated by PPAR. PMID- 22315586 TI - Time-dependent alterations in rat macrovessels with type 1 diabetes. AB - Vascular complications are associated with the progressive severity of diabetes, resulting in significant morbidity and mortality. This study quantifies functional vascular parameters and macrovascular structure in a rat model of type 1 diabetes. While there was no difference in the systemic arterial elastance (Ea) with 50 days of diabetes, changes were noted in the aorta and femoral artery including increased tunica media extracellular matrix content, decreased width of both the media and individual smooth muscle cell layers, and increased incidence of damaged mitochondria. Extracellular matrix proteins and elastin levels were significantly greater in the aorta of diabetic animals. These differences correlated with diminished matrix metalloprotease activity in the aorta of the diabetic animals. In conclusion, diabetes significantly altered the structure and ultrastructure of the aorta and femoral artery before systemic changes in arterial elastance could be detected. PMID- 22315587 TI - Mutagenesis as a tool in plant genetics, functional genomics, and breeding. AB - Plant mutagenesis is rapidly coming of age in the aftermath of recent developments in high-resolution molecular and biochemical techniques. By combining the high variation of mutagenised populations with novel screening methods, traits that are almost impossible to identify by conventional breeding are now being developed and characterised at the molecular level. This paper provides a comprehensive overview of the various techniques and workflows available to researchers today in the field of molecular breeding, and how these tools complement the ones already used in traditional breeding. Both genetic (Targeting Induced Local Lesions in Genomes; TILLING) and phenotypic screens are evaluated. Finally, different ways of bridging the gap between genotype and phenotype are discussed. PMID- 22315588 TI - Development of New Candidate Gene and EST-Based Molecular Markers for Gossypium Species. AB - New source of molecular markers accelerate the efforts in improving cotton fiber traits and aid in developing high-density integrated genetic maps. We developed new markers based on candidate genes and G. arboreum EST sequences that were used for polymorphism detection followed by genetic and physical mapping. Nineteen gene-based markers were surveyed for polymorphism detection in 26 Gossypium species. Cluster analysis generated a phylogenetic tree with four major sub clusters for 23 species while three species branched out individually. CAP method enhanced the rate of polymorphism of candidate gene-based markers between G. hirsutum and G. barbadense. Two hundred A-genome based SSR markers were designed after datamining of G. arboreum EST sequences (Mississippi Gossypium arboreum EST-SSR: MGAES). Over 70% of MGAES markers successfully produced amplicons while 65 of them demonstrated polymorphism between the parents of G. hirsutum and G. barbadense RIL population and formed 14 linkage groups. Chromosomal localization of both candidate gene-based and MGAES markers was assisted by euploid and hypoaneuploid CS-B analysis. Gene-based and MGAES markers were highly informative as they were designed from candidate genes and fiber transcriptome with a potential to be integrated into the existing cotton genetic and physical maps. PMID- 22315589 TI - Crohn's disease imaging: a review. AB - Crohn's disease is a chronic granulomatous inflammatory disease of the gastrointestinal tract, which can involve almost any segment from the mouth to the anus. Typically, Crohn's lesions attain segmental and asynchronous distribution with varying levels of seriousness, although the sites most frequently involved are the terminal ileum and the proximal colon. A single gold standard for the diagnosis of CD is not available and the diagnosis of CD is confirmed by clinical evaluation and a combination of endoscopic, histological, radiological, and/or biochemical investigations. In recent years, many studies have been performed to investigate the diagnostic potential of less invasive and more patient-friendly imaging modalities in the evaluation of Crohn's disease including conventional enteroclysis, ultrasonography, color-power Doppler, contrast-enhanced ultrasonography, multidetector CT enteroclysis, MRI enteroclysis, and 99mTc-HMPAO-labeled leukocyte scintigraphy. The potential diagnostic role of each imaging modality has to be considered in different clinical degrees of the disease, because there is no single imaging technique that allows a correct diagnosis and may be performed with similar results in every institution. The aim of this paper is to point out the advantages and limitations of the various imaging techniques in patients with suspected or proven Crohn's disease. PMID- 22315590 TI - E. coli-produced BMP-2 as a chemopreventive strategy for colon cancer: a proof-of concept study. AB - Colon cancer is a serious health problem, and novel preventive and therapeutical avenues are urgently called for. Delivery of proteins with anticancer activity through genetically modified bacteria provides an interesting, potentially specific, economic and effective approach here. Interestingly, bone morphogenetic protein 2 (BMP-2) is an important and powerful tumour suppressor in the colon and is thus an attractive candidate protein for delivery through genetically modified bacteria. It has not been shown, however, that BMP production in the bacterial context is effective on colon cancer cells. Here we demonstrate that transforming E. coli with a cDNA encoding an ileal-derived mature human BMP-2 induces effective apoptosis in an in vitro model system for colorectal cancer, whereas the maternal organism was not effective in this respect. Furthermore, these effects were sensitive to cotreatment with the BMP inhibitor Noggin. We propose that prevention and treatment of colorectal cancer using transgenic bacteria is feasible. PMID- 22315591 TI - Bayesian Analysis of a Lipid-Based Physiologically Based Toxicokinetic Model for a Mixture of PCBs in Rats. AB - A lipid-based physiologically based toxicokinetic (PBTK) model has been developed for a mixture of six polychlorinated biphenyls (PCBs) in rats. The aim of this study was to apply population Bayesian analysis to a lipid PBTK model, while incorporating an internal exposure-response model linking enzyme induction and metabolic rate. Lipid-based physiologically based toxicokinetic models are a subset of PBTK models that can simulate concentrations of highly lipophilic compounds in tissue lipids, without the need for partition coefficients. A hierarchical treatment of population metabolic parameters and a CYP450 induction model were incorporated into the lipid-based PBTK framework, and Markov-Chain Monte Carlo was applied to in vivo data. A mass balance of CYP1A and CYP2B in the liver was necessary to model PCB metabolism at high doses. The linked PBTK/induction model remained on a lipid basis and was capable of modeling PCB concentrations in multiple tissues for all dose levels and dose profiles. PMID- 22315592 TI - Compromised Rat Testicular Antioxidant Defence System by Hypothyroidism before Puberty. AB - Altered thyroid function during early stages of development is known to affect adversely testicular growth, physiology, and antioxidant defence status at adulthood. The objective of the present study is to investigate the modulation of antioxidant defence status in neonatal persistent hypothyroid rats before their sexual maturation and also to identify the specific testicular cell populations vulnerable to degeneration during neonatal hypothyroidism in immature rats. Hypothyroidism was induced in neonates by feeding the lactating mother with 0.05% 6-n-propyl-2-thiouracil (PTU) through the drinking water. From the day of parturition till weaning (25 day postpartum), the pups received PTU through mother's milk (or) drinking water and then directly from drinking water containing PTU for the remaining period of experimentation. On the 31st day postpartum, the animals were sacrificed for the study. An altered antioxidant defence system marked by elevated SOD, CAT, and GR activities, with decreased GPx and GST activities were observed along with increased protein carbonylation, disturbed redox status in hypothyroid immature rat testis. This compromised testicular antioxidant status might have contributed to poor growth and development by affecting the spermatogenesis and steroidogenesis in rats before puberty as indicated by reduced germ cell number, complete absence of round spermatids, decreased seminiferous tubule diameter, and decreased testosterone level. PMID- 22315593 TI - Delayed Recognition of Disorders of Sex Development (DSD): A Missed Opportunity for Early Diagnosis of Malignant Germ Cell Tumors. AB - Disorders of sex development (DSD) are defined as a congenital condition in which development of chromosomal, gonadal or anatomical sex is atypical. DSD patients with gonadal dysgenesis or hypovirilization, containing part of the Y chromosome (GBY), have an increased risk for malignant type II germ cell tumors (GCTs: seminomas and nonseminomas). DSD may be diagnosed in newborns (e.g., ambiguous genitalia), or later in life, even at or after puberty. Here we describe three independent male patients with a GCT; two were retrospectively recognized as DSD, based on the histological identification of both carcinoma in situ and gonadoblastoma in a single gonad as the cancer precursor. Hypospadias and cryptorchidism in their history are consistent with this conclusion. The power of recognition of these parameters is demonstrated by the third patient, in which the precursor lesion was diagnosed before progression to invasiveness. Early recognition based on these clinical parameters could have prevented development of (metastatic) cancer, to be treated by systemic therapy. All three patients showed a normal male 46,XY karyotype, without obvious genetic rearrangements by high-resolution whole-genome copy number analysis. These cases demonstrate overlap between DSD and the so-called testicular dysgenesis syndrome (TDS), of significant relevance for identification of individuals at increased risk for development of a malignant GCT. PMID- 22315594 TI - Definitive Radiotherapy versus Postoperative Radiotherapy of Patients with Oro- and Hypopharyngeal Cancer: Impact of Prognostic Factors. AB - Purpose. To compare the impact of prognostic factors of patients treated with definitive radio(chemo)therapy versus patients treated with surgery and postoperative radiotherapy for squamous cell carcinoma of the oro- and hypopharynx. Patients and Methods. 162 patients treated with definitive radiotherapy and 126 patients treated with postoperative radiotherapy were retrospectively analysed. The impact of the prognostic factors gender, age, total tumor volume (TTV), pre-radiotherapy hemoglobin level (Hb-level), tumor site, T- and N-classification, radiotherapy interruptions >5 days, radiotherapy versus simultaneous radiochemotherapy, R-status and time interval between surgery and radiotherapy were investigated. Results. The median follow-up time for the censored patients treated with definitive radio(chemo)therapy was 28.5 months and for postoperative radiotherapy 36.5 months. On univariate analysis, the TTV, Hb level, and simultaneous radiochemotherapy had a significant impact on the survival of patients treated with definitive radio(chemo)therapy. For patients treated with postoperative radiotherapy, only the TTV showed a statistical trend for the survival (P = 0.13). On multivariate analysis, the TTV and simultaneous radiochemotherapy maintained their statistical significance for patients treated with definitive raditherapy, and the TTV, the statistical trend for patients treated with postoperative radiotherapy (P = 0.19). Conclusions. The TTV was the predominant prognostic factor for both, patients treated with definitive or postoperative radiotherapy. PMID- 22315595 TI - Influence of morphine on pericyte-endothelial interaction: implications for antiangiogenic therapy. AB - Morphine stimulates tumor angiogenesis and cancer progression in mice. We examined if morphine influences endothelial-pericyte interaction via platelet derived growth factor-BB (PDGF-BB) and PDGF receptor-beta (PDGFR-beta). Clinically relevant doses of morphine stimulated PDGF-BB secretion from human umbilical vein endothelial cells and activated PDGFR-beta and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) phosphorylation in human pericytes. These in vitro effects of morphine were translated into promotion of tumor angiogenesis in a transgenic mice model of breast cancer when treated with clinically used dose of morphine. Increased vessel-associated immunoreactivity of desmin and PDGFR-beta was observed on pericytes in tumors of morphine-treated mice. These data suggest that morphine potentiates endothelial pericyte interaction via PDGF-BB/PDGFR-beta signaling and promotes tumor angiogenesis, pericyte recruitment, and coverage of tumor vessels. We speculate that morphine may impair the effectiveness of antiangiogenic therapy by influencing vascular pericyte coverage. PMID- 22315596 TI - Complex etiology underlies risk and survival in head and neck cancer human papillomavirus, tobacco, and alcohol: a case for multifactor disease. AB - Findings are inconsistent about whether tobacco, alcohol, and human papillomavirus (HPV) are two independent HNC risk factor groups that distinguish an infection-associated cancer from a tobacco/alcohol-associated HNC. We found that cancer in the oral cavity risk was greater in HPV-E6/E7 seropositive/heavy tobacco users (adjusted OR = 3.5) than in HPV-seronegative/heavy tobacco users (adjusted OR = 1.4); and HPV-seropositive/heavy alcohol users (adjusted OR = 9.8) had greater risk than HPV-seronegative/heavy alcohol users (adjusted OR = 3.1). In contrast, the risk of oropharyngeal cancer was greater in the HPV seronegative/heavy tobacco (adjusted OR = 11.0) than in HPV-seropositive/heavy tobacco (adjusted OR = 4.7) users and greater in HPV-seronegative/heavy alcohol users (adjusted OR = 24.3) compared to HPV-seropositive/heavy alcohol users (adjusted OR = 8.5). Disease-specific and recurrence-free adjusted survival were significantly worse in oropharyngeal HPV-seronegative cases with no survival differences by HPV status seen in oral cavity cases. The association between tobacco/alcohol, HPV, and tumor site is complex. There appear to be distinct tumor site differences in the combined exposure risks, suggesting that different molecular pathways are involved. PMID- 22315598 TI - HAX1 Augments Cell Proliferation, Migration, Adhesion, and Invasion Induced by Urokinase-Type Plasminogen Activator Receptor. AB - The urokinase-type plasminogen activator receptor (uPAR) is a cell surface receptor which has a multifunctional task in the process of tumorigenesis including cell proliferation, adhesion, migration, and invasion. Many of the biological functions of uPAR necessitate interactions with other proteins. We have shown previously that uPAR interacts with HAX1 protein (HS-1-associated protein X-1). In the current study, to gain insight into the possible role of HAX1 overexpression in regulation of uPAR signal transduction pathway, several function assays were used. We found that, upon stimulation of uPAR, HAX1 colocalizes with uPAR suggesting a physiological role for HAX1 in the regulation of uPAR signal transduction. HAX1 overexpression augments cell proliferation and migration in uPAR-stimulated cells. Moreover, HAX1 over-expression augmented uPAR induced cell adhesion to vitronectin as well as cellular invasion. Our results suggest that HAX1 over-expression may underlay a novel mechanism to regulate uPAR induced functions in cancer cells. PMID- 22315597 TI - WAVE2 Protein Complex Coupled to Membrane and Microtubules. AB - E-cadherin is one of the key molecules in the formation of cell-cell adhesion and interacts intracellularly with a group of proteins collectively named catenins, through which the E-cadherin-catenin complex is anchored to actin-based cytoskeletal components. Although cell-cell adhesion is often disrupted in cancer cells by either genetic or epigenetic alterations in cell adhesion molecules, disruption of cell-cell adhesion alone seems to be insufficient for the induction of cancer cell migration and invasion. A small GTP-binding protein, Rac1, induces the specific cellular protrusions lamellipodia via WAVE2, a member of WASP/WAVE family of the actin cytoskeletal regulatory proteins. Biochemical and pharmacological investigations have revealed that WAVE2 interacts with many proteins that regulate microtubule growth, actin assembly, and membrane targeting of proteins, all of which are necessary for directional cell migration through lamellipodia formation. These findings might have important implications for the development of effective therapeutic agents against cancer cell migration and invasion. PMID- 22315599 TI - Human Coronaviruses HCoV-NL63 and HCoV-HKU1 in Hospitalized Children with Acute Respiratory Infections in Beijing, China. AB - The human coronaviruses (HCoVs) HCoV-NL63 and HCoV-HKU1 are two recently discovered coronaviruses that circulate widely and are associated with acute respiratory infections (ARI). We detected HCoV-NL63 and HCoV-HKU1 in specimens collected from May 2008 to March 2010 from patients with ARI aged <7.75 years of age attending the Beijing Children's Hospital. Thirty-two (8.4%) and 57 (14.9%) of 382 specimens tested positive for HCoV-NL63 and HCoV-HKU1, respectively, by real-time RT-PCR. Use of a Luminex xTAG RVP Fast kit showed that coinfection with respiratory syncytial virus and parainfluenza 3 virus was common among patients infected with either virus type. In HCoV-HKU1-infected patients, the predominant clinical symptoms were cough, fever, and expectoration. In HCoV-NL63-infected patients they were cough, fever, and rhinorrhea. Phylogenetic studies showed that the HCoV-HKU1 nucleoprotein gene was relatively conserved compared to NCBI reference sequences, while the 1ab gene of HCoV-NL63 showed more variation. PMID- 22315601 TI - The evolutionary processes of canine coronaviruses. AB - Since the first identification of the virus in 1971, the disease caused by canine coronavirus (CCoV) has not been adequately investigated, and the role that the virus plays in canine enteric illness has not been well established. Only after the emergence in 2002 of SARS in human has new attention been focused on coronaviruses. As a consequence of the relatively high mutation frequency of RNA positive stranded viruses, CCoV has evolved and, with the biomolecular techniques developed over the last two decades, new virus strains, serotypes, and subtypes have been identified in infected dogs. Considering the widespread nature of CCoV infections among dog populations, several studies have been carried out, focusing upon the epidemiological relevance of these viruses and underlining the need for further investigation into the biology of CCoVs and into the pathogenetic role of the infections. This paper reports the evolutionary processes of CCoVs with a note onto recent diagnostic methods. PMID- 22315600 TI - Phylogeny-directed search for murine leukemia virus-like retroviruses in vertebrate genomes and in patients suffering from myalgic encephalomyelitis/chronic fatigue syndrome and prostate cancer. AB - Gammaretrovirus-like sequences occur in most vertebrate genomes. Murine Leukemia Virus (MLV) like retroviruses (MLLVs) are a subset, which may be pathogenic and spread cross-species. Retroviruses highly similar to MLLVs (xenotropic murine retrovirus related virus (XMRV) and Human Mouse retrovirus-like RetroViruses (HMRVs)) reported from patients suffering from prostate cancer (PC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) raise the possibility that also humans have been infected. Structurally intact, potentially infectious MLLVs occur in the genomes of some mammals, especially mouse. Mouse MLLVs contain three major groups. One, MERV G3, contained MLVs and XMRV/HMRV. Its presence in mouse DNA, and the abundance of xenotropic MLVs in biologicals, is a source of false positivity. Theoretically, XMRV/HMRV could be one of several MLLV transspecies infections. MLLV pathobiology and diversity indicate optimal strategies for investigating XMRV/HMRV in humans and raise ethical concerns. The alternatives that XMRV/HMRV may give a hard-to-detect "stealth" infection, or that XMRV/HMRV never reached humans, have to be considered. PMID- 22315602 TI - Near-full genome characterisation of two natural intergenotypic 2k/1b recombinant hepatitis C virus isolates. AB - Few natural intergenotypic hepatitis C virus (HCV) recombinants have been characterised, and only RF1_2k/1b has demonstrated widespread transmission. The near-full length genome sequences for two cases of 2k/1b recombinants (CYHCV037 and CYHCV093) sampled in Cyprus were obtained using strain-specific RT-PCR amplification and sequencing protocols. Sequence analysis confirmed their similarity with the original RF1_2k/1b strain from St. Petersburg, N687. These two isolates significantly contribute to the sequence data available on this recombinant and confirm its increasing spread among individuals from Eastern Europe, and its association with transmission through intravenous drug use. Phylogenetic analyses reveal clustering of the sequence 3' to the recombination point, not seen in the topology of the 5' sequences, implying a more complicated evolutionary history than that held to date. The increasing cases of HCV recombinant strains underline the requirement of their contribution to the standardised rules of HCV classification and nomenclature, molecular epidemiology, diagnosis, and treatment. PMID- 22315603 TI - Localization of basicranium midline by submentovertex projection for the evaluation of condylar asymmetry. AB - The purpose of this research was to compare the reliability of two different methods for cranial midline localization through cephalometric analysis of mandibular condyle asymmetries. A retrospective cohort study was performed analyzing consecutively the SMV radiograms of 47 patients undergoing oral surgery before orthodontic treatment at the Dental School, University of Trieste (Italy) from 2003 to 2008. Two different cephalometric analyses were used to identify the basicranium midline (Tracing 1: initial landmarks = craniostat ear rods; Tracing 2: initial landmarks = spinosum foramina), and the left/right symmetry ratio (SR) for four parameters (condylar length, condylar angle, intra-condylar hemidistance, extra-condylar hemidistance) was calculated. The main result showed that no significant statistical difference between the SRs of the intra-condylar and extra-condylar hemidistance obtained with the same tracing was found (t-test; P = NS; C.I. 95%). Conversely, the difference between the SRs obtained with the two different tracings was statistically significant (t-test; P < 0.000; C.I. 95%). In conclusion, if the analysis of condylar asymmetries is performed in growing subjects, utilization of anatomic references such as the neurovascular foramina seems to guarantee a lower error compared to non-fixed references such as ear rods. PMID- 22315604 TI - Current status and future development of cell transplantation therapy for periodontal tissue regeneration. AB - It has been shown that stem cell transplantation can regenerate periodontal tissue, and several clinical trials involving transplantation of stem cells into human patients have already begun or are in preparation. However, stem cell transplantation therapy is a new technology, and the events following transplantation are poorly understood. Several studies have reported side effects and potential risks associated with stem cell transplantation therapy. To protect patients from such risks, governments have placed regulations on stem cell transplantation therapies. It is important for the clinicians to understand the relevant risks and governmental regulations. This paper describes the ongoing clinical studies, basic research, risks, and governmental controls related to stem cell transplantation therapy. Then, one clinical study is introduced as an example of a government-approved periodontal cell transplantation therapy. PMID- 22315605 TI - Chromosomal damage and apoptosis in exfoliated buccal cells from individuals with oral cancer. AB - This study aimed to investigate cytological abnormalities indicative of chromosome damage (micronuclei) and apoptosis (karyorrhexis, pyknosis, and condensed chromatin) in exfoliated cells from the buccal mucosa of patients with oral cancer and control subjects. The sample included twenty individuals with oral cancer and forty individuals with normal buccal mucosa. Material was collected from the cheek epithelium in areas with lesions and areas without abnormalities. A minimum of one thousand cells was analyzed. Micronuclei were found significantly more frequently in cells collected from lesions than in cells from normal areas, independent of the presence/absence of cancer (P < 0.0001). They were also significantly more frequent in smokers and in mouthwash users (P < 0.0001). Apoptosis occurred significantly less frequently in individuals with oral cancer (P < 0.0001). These results show that oral cancer is associated with higher frequency of chromosomal damage and suggest that apoptosis is compromised in the buccal cells of individuals with this kind of neoplasia. PMID- 22315606 TI - Adhesion of Porphyromonas gingivalis and Biofilm Formation on Different Types of Orthodontic Brackets. AB - Objectives. To examine the interaction between Porphyromonas gingivalis and 3 different orthodontic brackets in vitro, focusing on the effect of an early salivary pellicle and other bacteria on the formation of biofilms. Material and Methods. Mono- and multi-species P. gingivalis biofilms were allowed to form in vitro, on 3 different bracket types (stainless steel, ceramic and plastic) with and without an early salivary pellicle. The brackets were anaerobically incubated for 3 days in Brain Heart Infusion Broth to form biofilms. Bacteria were quantified by trypsin treatment and enumeration of the total viable counts of bacteria recovered. Results. Saliva was found to significantly affect (P < 0.001) adhesion and biofilm formation of P. gingivalis, with higher numbers for the coated brackets. No significant effect was detected for the impact of the type of biofilm, although on stainless steel and plastic brackets there was a tendency for higher numbers of the pathogen in multi-species biofilms. Bracket material alone was not found to affect the number of bacteria. Conclusions. The salivary pellicle seems to facilitate the adhesion of P. gingivalis and biofilm formation on orthodontic brackets, while the material comprising the brackets does not significantly impact on the number of bacteria. PMID- 22315607 TI - Evaluation of the effect of water on three different light cured composite restorative materials stored in water: an in vitro study. AB - Objectives. The objective of this in vitro study was to investigate whether weight gain or loss in the three different composites occurs due to water absorption when they are stored in water. Methods. The composite restorative materials selected for this study included a microfine hybrid (Synergy) and two nanofilled composite restorative materials (Ceram X and Filtek Supreme Ultra). Twenty specimens of each material were fabricated of each composite material. Group A: Filtek Supreme Ultra, Group B: Synergy, Group C: Ceram X. Then all the specimens were stored in 10 ml Distilled water containing test tubes and placed in incubator at 37 degrees C for six weeks. The weight changes of these specimens were measured daily for the first week and later once a week for next five weeks by using an electrical analytical balance. Results. The data was analyzed by one way analysis of variance and Student's t test. All groups showed maximum amount of water absorption in the first week than gradual decrease in the water absorption from the second to the sixth week, as compared to the first week and there is no statistically significant difference between the groups tested. Conclusion. All the composite restorative material absorbs some amount of water. The water absorption of the composite may decrease the physical and mechanical properties of the composites; hence it is necessary to consider the type of the material before starting the treatment. PMID- 22315608 TI - Biologically based restorative management of tooth wear. AB - The prevalence and severity of tooth wear is increasing in industrialised nations. Yet, there is no high-level evidence to support or refute any therapeutic intervention. In the absence of such evidence, many currently prevailing management strategies for tooth wear may be failing in their duty of care to first and foremost improve the oral health of patients with this disease. This paper promotes biologically sound approaches to the management of tooth wear on the basis of current best evidence of the aetiology and clinical features of this disease. The relative risks and benefits of the varying approaches to managing tooth wear are discussed with reference to long-term follow-up studies. Using reference to ethical standards such as "The Daughter Test", this paper presents case reports of patients with moderate-to-severe levels of tooth wear managed in line with these biologically sound principles. PMID- 22315609 TI - Pericoronal follicles of asymptomatic impacted teeth: a radiographic, histomorphologic, and immunohistochemical study. AB - Objective. To associate radiographic and histopathological features of pericoronal follicles (PFs) of asymptomatic impacted teeth and evaluate cell proliferation and apoptosis in the epithelium. Study Design. Epithelium and mesenchyme of radiographically normal (NPF <= 2.5 mm) and hyperplastic (HPF 2.6 to 5 mm) PF (n = 140) were studied histologically. Cell proliferation (PI) and epithelial apoptosis were evaluated by Ki-67 and bcl-2 expression in 14 NPFs and 10 dentigerous cysts (DCs). Results. Radiographically, 127 were NPFs and 13 were HPFs; 87.8% of total PFs exhibited epithelium on the surface. Reduced enamel epithelium was observed in 78 (61.4%) NPFs and 6 (46.2%) HPFs, squamous metaplasia in 17 (13.4%) NPFs and 4 (30.8%) HPFs, and cystic epithelium in 15 (11.8%) NPFs and 3 (23%) HPFs. Mean PI was 1.97 +/- 1.25 and 7.97 +/- 1.74 in the epithelial component of NPF and DC, respectively; bcl-2 positive expression was observed in 9 (64.3%) NPFs and 7 (70%) DCs. Conclusion. The scant epithelial remnant proliferation could imply low risk for development of odontogenic pathologies in the absence of an additional stimulus. PMID- 22315610 TI - Deformation Behavior of Human Dentin under Uniaxial Compression. AB - Deformation behavior of a human dentin under compression including size and rate effects is studied. No difference between mechanical properties of crown and root dentin is found. It is mechanically isotropic high elastic and strong hard tissue, which demonstrates considerable plasticity and ability to suppress a crack growth. Mechanical properties of dentin depend on a shape of samples and a deformation rate. PMID- 22315612 TI - Isolation of cellulose-degrading bacteria and determination of their cellulolytic potential. AB - Eight isolates of cellulose-degrading bacteria (CDB) were isolated from four different invertebrates (termite, snail, caterpillar, and bookworm) by enriching the basal culture medium with filter paper as substrate for cellulose degradation. To indicate the cellulase activity of the organisms, diameter of clear zone around the colony and hydrolytic value on cellulose Congo Red agar media were measured. CDB 8 and CDB 10 exhibited the maximum zone of clearance around the colony with diameter of 45 and 50 mm and with the hydrolytic value of 9 and 9.8, respectively. The enzyme assays for two enzymes, filter paper cellulase (FPC), and cellulase (endoglucanase), were examined by methods recommended by the International Union of Pure and Applied Chemistry (IUPAC). The extracellular cellulase activities ranged from 0.012 to 0.196 IU/mL for FPC and 0.162 to 0.400 IU/mL for endoglucanase assay. All the cultures were also further tested for their capacity to degrade filter paper by gravimetric method. The maximum filter paper degradation percentage was estimated to be 65.7 for CDB 8. Selected bacterial isolates CDB 2, 7, 8, and 10 were co-cultured with Saccharomyces cerevisiae for simultaneous saccharification and fermentation. Ethanol production was positively tested after five days of incubation with acidified potassium dichromate. PMID- 22315611 TI - The plasma membrane potential and the organization of the actin cytoskeleton of epithelial cells. AB - The establishment and maintenance of the polarized epithelial phenotype require a characteristic organization of the cytoskeletal components. There are many cellular effectors involved in the regulation of the cytoskeleton of epithelial cells. Recently, modifications in the plasma membrane potential (PMP) have been suggested to participate in the modulation of the cytoskeletal organization of epithelia. Here, we review evidence showing that changes in the PMP of diverse epithelial cells promote characteristic modifications in the cytoskeletal organization, with a focus on the actin cytoskeleton. The molecular paths mediating these effects may include voltage-sensitive integral membrane proteins and/or peripheral proteins sensitive to surface potentials. The voltage dependence of the cytoskeletal organization seems to have implications in several physiological processes, including epithelial wound healing and apoptosis. PMID- 22315613 TI - Isolation, purification, and characterization of xylanase produced by a new species of bacillus in solid state fermentation. AB - A thermoalkalophilic new species of Bacillus, similar to Bacillus arseniciselenatis DSM 15340, produced extracellular xylanase under solid state fermentation when wheat bran is used as carbon source. The extracellular xylanase was isolated by ammonium sulfate (80%) precipitation and purified using ion exchange chromatography. The molecular weight of xylanase was ~29.8 kDa. The optimum temperature and pH for the enzyme activity were 50 degrees C and pH 8.0. The enzyme was active on birchwood xylan and little active on p-nitrophenyl xylopyranoside but not on Avicel, CMC, cellobiose, and starch, showing its absolute substrate specificity. For birchwood xylan, the enzyme gave a Km 5.26 mg/mL and Vmax 277.7 MUmol/min/mg, respectively. In addition, the xylanase was also capable of producing high-quality xylo-oligosaccharides, which indicated its application potential not only in pulp biobleaching processes but also in the nutraceutical industry. PMID- 22315614 TI - Cotrimoxazole Prophylaxis Specifically Selects for Cotrimoxazole Resistance in Streptococcus mutans and Streptococcus sobrinus with Varied Polymorphisms in the Target Genes folA and folP. AB - The selection of antibiotic resistance by cotrimoxazole prophylaxis was evaluated, and we characterized the mechanism of cotrimoxazole resistance in Streptococcus mutans and Streptococcus sobrinus. In vitro susceptibility to six antibiotics was evaluated on 64 mutans streptococci group (MSG) isolates from a cotrimoxazole prophylaxis group and compared to 84 MSG isolates from a nonprophylaxis group. The folA and folP genes were sequenced and compared with reference sequences at NCBI. Only resistance to cotrimoxazole was significantly higher in the prophylaxis group (54.7% versus 15.5%, OR = 6.59, 95% CI: 2.89 15.3, P < 0.05). Resistance to amoxicillin, ceftriaxone, chloramphenicol, erythromycin, and tetracycline was 1.4%, 25.5%, 6.2%, 6.5%, and 29.6% of the isolates, respectively. Considerable polymorphisms were found in the folP gene in S. mutans, but this could not be linked to sulfonamide drug resistance. No variation was seen in folP or folA genes of S. sobrinus. Genetic transfer of folate pathway genes seems unlikely in these isolates. PMID- 22315616 TI - The effects of maternal supplementation of polyunsaturated Fatty acids on visual, neurobehavioural, and developmental outcomes of the child: a systematic review of the randomized trials. AB - Polyunsaturated fatty acid (PUFA) use in pregnancy has been promoted as beneficial for visual and neurobehavioural development in the fetus. However, no systematic review of the randomized trials has been conducted. The objective of this review was to evaluate potential advantages of this regiment by reviewing all randomized trials in pregnancy. Methods. Systematic review of randomized controlled studies comparing cognitive and visual achievements among infants whose mothers were treated and untreated with PUFA during gestation. Results. Nine studies met the inclusion criteria, three focusing on visual and six on neurobehavioural development. Due to differing outcome measurements in the infants, the studies could not be combined into a formal meta-analysis. Synthesizing the existing data, for both visual and neurobehavioural development, most studies could not show sustained benefits to infant cognition or visual development. Conclusion. At the present time a recommendation to change practice and supplement all expecting mothers with PUFA to improve offspring vision or neurobehavioural function is not supported by existing evidence. PMID- 22315615 TI - Tocilizumab for the treatment of rheumatoid arthritis and other systemic autoimmune diseases: current perspectives and future directions. AB - Interleukin (IL)-6 is a cytokine featuring redundancy and pleiotropic activity. While IL-6, when transiently produced, contributes to host defense against acute environmental stress, continuous dysregulated IL-6 production plays a significant pathological role in several systemic autoimmune diseases. In response to the expectation that IL-6 blockade would constitute a novel therapeutic strategy for the treatment of these diseases, tocilizumab, a humanized anti-IL-6 receptor antibody, was developed. Clinical trials have verified the efficacy and the safety of tocilizumab for patients with rheumatoid arthritis, resulting in approval of this innovative biologic for the treatment of rheumatoid arthritis in more than 90 countries worldwide. Pathological analyses of the effect of IL-6 on the development of autoimmune diseases and a considerable number of case reports and pilot studies have also indicated the beneficial effects of this antibody on other systemic autoimmune diseases, including systemic lupus erythematosus, systemic sclerosis, polymyositis, and large-vessel vasculitis. PMID- 22315618 TI - The effect of human and mouse fibroblast feeder cells on cardiac differentiation of human pluripotent stem cells. AB - Mouse embryonic fibroblasts (MEFs) and human foreskin fibroblasts (hFFs) are commonly used as feeder cells to maintain the pluripotent state of stem cells. The aim of the present study was to evaluate the effect of MEF and hFF feeders on the cardiac differentiation. Two human embryonic and two induced pluripotent stem cell lines were cultured on MEF and hFF before cardiac differentiation. The expression of Brachyury T was higher in cell lines cultured on MEF, than if cultured on hFF, suggesting enhanced mesoderm formation. However, significant positive influence of MEF feeders on cardiac differentiation was only seen with one cell line. Further, the ability of hFF to maintain pluripotency of stem cells originally cultured on MEF was quite poor. In conclusion, the cells behaved differently whether cultured on hFF or MEF feeders. However, the influence of the feeder cells on differentiation was less than the difference observed between the cell lines. PMID- 22315617 TI - Mesenchymal stem cells and cardiovascular disease: a bench to bedside roadmap. AB - In recent years, the incredible boost in stem cell research has kindled the expectations of both patients and physicians. Mesenchymal progenitors, owing to their availability, ease of manipulation, and therapeutic potential, have become one of the most attractive options for the treatment of a wide range of diseases, from cartilage defects to cardiac disorders. Moreover, their immunomodulatory capacity has opened up their allogenic use, consequently broadening the possibilities for their application. In this review, we will focus on their use in the therapy of myocardial infarction, looking at their characteristics, in vitro and in vivo mechanisms of action, as well as clinical trials. PMID- 22315619 TI - Microspatial distributional patterns of vectors of cutaneous leishmaniasis in pernambuco, northeastern Brazil. AB - The purpose of this study is to analyze the spatial distribution and population trends through time of Lutzomyia species in a long-term focus of cutaneous leishmaniasis transmission in an Atlantic Forest area, northeastern Brazil. Sand fly populations of different ecological niches were monitored spatiotemporally in 2009. To summarize vegetation characteristics and phenology, we calculated the Normalized Difference Vegetation Index from Landsat images. Using niche modeling approaches, we assessed suites of environmental factors to identify areas of transmission risk. Although 12 species were detected, L. whitmani was the most abundant and broadly distributed across the area, particularly in peridomiciliary locations, and associated negatively with denser vegetation areas. On the other hand, L. complexa, L. sordelli, and L. tupynambai were found almost exclusively in forested areas (P < 0.05), and associated positively with denser vegetation. Lutzomyia species' occurrences are related to specific environmental combinations (with contrast among species) in the region. PMID- 22315620 TI - Distribution and abundance of phlebotominae, vectors of leishmaniasis, in Argentina: spatial and temporal analysis at different scales. AB - The spatial-temporal analysis of the abundance of insects, vectors of tegumentary leishmaniasis (TL) and visceral leishmaniasis (VL), was performed in Argentina using spatial-temporal increasing scales. In the microscale (microfocal), the effect of the primary vegetation-crop interface in vector abundance was observed, and also how the shelters, food sources, and other environmental characteristics contribute to habitat microheterogeneity and so to a microheterogeneous vector distribution. In the mesoscale (locality or epidemic focus), the results from different foci of TL (rural and periurban) and VL (urban) suggested a metapopulation structure determined partially by quantifiable habitat variables that could explain the increase of risk associated to an increase of vector-human contact due to climatic or anthropogenic changes. In the macroscale (regional), captures of vectors and records of human cases allowed the construction of risk maps and predictive models of vector distribution. In conclusion, in order to obtain valid results transferrable to control programs from spatial studies, special attention should be paid in order to assure the consistency between the spatial scales of the hypotheses, data, and analytical tools of each experimental or descriptive design. PMID- 22315621 TI - Studies on the Feeding Habits of Lutzomyia (Lutzomyia) longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae) Populations from Endemic Areas of American Visceral Leishmaniasis in Northeastern Brazil. AB - The aim of this study was to identify potential blood feeding sources of L. (L.) longipalpis specimens from populations in Northeastern Brazil, endemic areas of American Visceral Leishmaniasis (AVL) and its correlation with the transmission of L. (L.) i. chagasi. The ELISA technique was applied using bird, dog, goat, opossum, equine, feline, human, sheep, and rodent antisera to analyze 609 females, resulting in an overall positivity of 60%. In all municipalities, females showed higher positivity for bird followed by dog antiserum and sand fly specimens were also positive for equine, feline, human, sheep, goat, opossum, and rodent antisera. The finding for 17 combinations of two or three types of blood in some females corroborates the opportunistic habit of this sand fly species. The results demonstrating the association between L. (L.) longipalpis and opossum suggest the need for further evaluation of the real role of this synanthropic mammal in the eco-epidemiology of AVL. PMID- 22315622 TI - Kidney disease and youth onset type 2 diabetes: considerations for the general practitioner. AB - Youth onset type 2 diabetes (T2DM) continues to increase worldwide, concomitant with the rising obesity epidemic. There is evidence to suggest that youth with T2DM are affected by the same comorbidities and complications as adults diagnosed with T2DM. This review highlights specifically the kidney disease associated with youth onset T2DM, which is highly prevalent and associated with a high risk of end-stage kidney disease in early adulthood. A general understanding of this complex disease by primary care providers is critical, so that at-risk individuals are identified and managed early in the course of their disease, such that progression can be modified in this high-risk group of children and adolescents. A review of the pediatric literature will include a focus on the epidemiology, risk factors, pathology, screening, and treatment of kidney disease in youth onset T2DM. PMID- 22315623 TI - Cardiorespiratory fitness, metabolic risk, and inflammation in children. AB - The aim of this study was to investigate the independent associations among cardiorespiratory fitness, metabolic syndrome (MetS), and C-reactive protein (CRP) in children. The sample consisted of 112 children (11.4 +/- 0.4 years). Data was obtained for children's anthropometry, cardiorespiratory fitness, MetS components, and CRP levels. MetS was defined using criteria analogous to the Adult Treatment Panel III definition. A MetS risk score was also computed. Prevalence of the MetS was 5.4%, without gender differences. Subjects with low fitness showed significantly higher MetS risk (P < 0.001) and CRP (P < 0.007), compared to the high-fitness pupils. However, differences in MetS risk, and CRP between fitness groups decreased when adjusted for waist circumference. These data indicate that the mechanisms linking cardiorespiratory fitness, MetS risk and inflammation in children are extensively affected by obesity. Intervention strategies aiming at reducing obesity and improving cardiorespiratory fitness in childhood might contribute to the prevention of the MetS in adulthood. PMID- 22315624 TI - Treatment of anterior cruciate ligament injury in skeletally immature patients. AB - The incidence of ACL tears is rising in the pediatric and adolescent populations as these individuals succumb to traumatic and nontraumatic athletic injuries. Management of this condition in the skeletally immature patient poses a challenge and is controversial. Operative reconstruction carries the concern for damage to the physis with resultant limb length inequality and angular joint deformity but provides stability to the knee and allows return of function in most patients. On the other hand, nonoperative treatment has been shown to carry an increased risk of meniscal and articular cartilage damage and is difficult from a compliance standpoint in this demographic. For the majority of skeletally immature patients, operative treatment is recommended as it has shown good clinical and functional results with minimal risk of growth disturbance. This paper aims to address the natural course of ACL injuries in the skeletally immature patient, treatment options with associated complications, and current preventative strategies. PMID- 22315625 TI - Mechanisms of remodeling in asthmatic airways. AB - Asthma is a chronic inflammatory airway disorder characterized by airway hyperresponsiveness and reversible airflow obstruction. Subgroups of asthma patients develop airflow obstruction that is irreversible or only partially reversible and experience an accelerated rate of lung function decline. The structural changes in the airways of these patients are referred to as airway remodeling. All elements of the airway wall are involved, and remodeled airway wall thickness is substantially increased compared to normal control airways. Airway remodeling is thought to contribute to the subphenotypes of irreversible airflow obstruction and airway hyperresponsiveness, and it has been associated with increased disease severity. Reversal of remodeling is therefore of paramount therapeutic importance, and mechanisms responsible for airway remodeling are feasible therapeutic targets for asthma treatment. This paper will focus on our current understanding of the mechanisms of airway remodeling in asthma and potential targets for future intervention. PMID- 22315627 TI - A safe protocol for amalgam removal. AB - Today's environment has different impacts on our body than previous generations. Heavy metals are a growing concern in medicine. Doctors and individuals request the removal of their amalgam (silver mercury) restorations due to the high mercury content. A safe protocol to replace the silver mercury filling will ensure that there is minimal if any absorption of materials while being removed. Strong alternative white composite and lab-processed materials are available today to create a healthy and functioning mouth. Preparation of the patient prior to the procedure and after treatment is vital to establish the excretion of the mercury from the body. PMID- 22315626 TI - Environmental determinants of chronic disease and medical approaches: recognition, avoidance, supportive therapy, and detoxification. AB - The World Health Organization warns that chronic, noncommunicable diseases are rapidly becoming epidemic worldwide. Escalating rates of neurocognitive, metabolic, autoimmune and cardiovascular diseases cannot be ascribed only to genetics, lifestyle, and nutrition; early life and ongoing exposures, and bioaccumulated toxicants may also cause chronic disease. Contributors to ill health are summarized from multiple perspectives--biological effects of classes of toxicants, mechanisms of toxicity, and a synthesis of toxic contributors to major diseases. Healthcare practitioners have wide-ranging roles in addressing environmental factors in policy and public health and clinical practice. Public health initiatives include risk recognition and chemical assessment then exposure reduction, remediation, monitoring, and avoidance. The complex web of disease and environmental contributors is amenable to some straightforward clinical approaches addressing multiple toxicants. Widely applicable strategies include nutrition and supplements to counter toxic effects and to support metabolism; as well as exercise and sweating, and possibly medication to enhance excretion. Addressing environmental health and contributors to chronic disease has broad implications for society, with large potential benefits from improved health and productivity. PMID- 22315629 TI - Inhibitory Effect of Polyphenol-Rich Fraction from the Bark of Acacia mearnsii on Itching Associated with Allergic Dermatitis. AB - We examined the inhibitory effect of polyphenol-rich aqueous extract from the bark of Acacia mearnsii (PrA) on itching associated with atopic dermatitis (AD). HR-1 mice were fed a normal diet, special diet (AD group), or special diet containing 3% PrA (PrA group) for 6 weeks. In the AD group, itching frequency and transepidermal water loss increased compared to the control group. In the PrA group, an improvement in atopic dermatitis symptoms was observed. Ceramide expression in the skin decreased in the AD group compared to the control group, but no decrease was observed in the PrA group. mRNA expression of ceramidase decreased in the PrA group compared to the AD group. The results of this study have revealed that PrA inhibits itching in atopic dermatitis by preventing the skin from drying. It is considered that the mechanism by which PrA prevents the skin from drying involves the inhibition of increased ceramidase expression associated with atopic dermatitis. PMID- 22315628 TI - Association between depressive symptoms and metabolic syndrome in police officers: results from two cross-sectional studies. AB - Policing is one of the most dangerous and stressful occupations and such stress can have deleterious effects on health. The purpose of this study was to examine the association between depressive symptoms and metabolic syndrome (MetSyn) in male and female police officers from two study populations, Buffalo, NY and Spokane, WA. Depressive symptoms were measured using the Center for Epidemiologic Studies-Depression (CES-D) scale. MetSyn was defined using the 2005 AHA/NHBLI guidelines. Analysis of covariance was used to describe differences in number of MetSyn components across depressive symptom categories. The number of MetSyn components increased significantly across categories of CES-D for Spokane men only (p-trend = 0.003). For each 5-unit increase in CES-D score, odds increased by 47.6% for having hypertriglyceridemia, by 51.8% for having hypertension, and by 56.7% for having glucose intolerance. Exploring this association is important since both are predictors of future chronic health problems and the results could be helpful in developing future gender-specific prevention and intervention efforts among police officers. PMID- 22315630 TI - Adverse drug reactions in a complementary medicine hospital: a prospective, intensified surveillance study. AB - Background. Anthroposophic medicine is one of the widely used approaches of complementary and alternative medicine. However, few prospective studies have generated safety data on its use. Objectives. We aimed to assess adverse drug reactions (ADRs) caused by anthroposophical medicines (AMEDs) in the anthroposophical Community Hospital Havelhoehe, GERMANY. Study Design and Methods. Between May and November 2007, patients of six medical wards were prospectively assessed for ADRs. Suspected ADRs occurring during hospitalization were documented and classified in terms of organ manifestation (WHO SOC-code), causality (according to the Uppsala Monitoring Centre WHO criteria), and severity. Only those ADRs with a severity of grade 2 and higher according to the CTCAE classification system are described here. Results. Of the 3,813 patients hospitalized, 174 patients (4.6%) experienced 211 ADRs (CTCAE grade 2/3 n = 191, 90.5%, CTCAE grade 4/5 n = 20, 9.5%) of which 57 ADRs (27.0%) were serious. The median age of patients with ADRs (62.1% females) was 72.0 (IQR: 61.0; 80.0). Six patients (0.2%) experienced six ADRs (2.8% of ADRs) caused by eight suspected AMEDs, all of which were mild reactions (grade 2). Conclusion. Our data show that ADRs caused by AMEDs occur rarely and are limited to mild symptoms. PMID- 22315631 TI - Wound Healing and Anti-Inflammatory Effect in Animal Models of Calendula officinalis L. Growing in Brazil. AB - Calendula officinalis is an annual herb from Mediterranean origin which is popularly used in wound healing and as an anti-inflammatory agent. In this study, the ethanolic extract, the dichloromethane, and hexanic fractions of the flowers from plants growing in Brazil were produced. The angiogenic activity of the extract and fractions was evaluated through the chorioallantoic membrane and cutaneous wounds in rat models. The healing activity of the extract was evaluated by the same cutaneous wounds model through macroscopic, morphometric, histopathologic, and immunohistochemical analysis. The antibacterial activity of the extract and fractions was also evaluated. This experimental study revealed that C. officinalis presented anti-inflammatory and antibacterial activities as well as angiogenic and fibroplastic properties acting in a positive way on the inflammatory and proliferative phases of the healing process. PMID- 22315632 TI - Honey-based mixtures used in home medicine by nonindigenous population of misiones, Argentina. AB - Honey-based mixtures used in home medicine by nonindigenous population of Misiones, Argentina. Medicinal mixtures are an underinvestigated issue in ethnomedical literature concerning Misiones, one of the most bioculturally diverse province of Argentina. The new culturally sensitive politics of the Provincial Health System is a response to cultural practices based on the medicinal use of plant and animal products in the home medicine of the local population. Honey-based medicinal formulas were investigated through interviews with 39 farmers of mixed cultural (Criollos) and Polish origins in northern Misiones. Fifty plant species and 8 animal products are employed in honey-based medicines. Plants are the most dominant and variable elements of mixtures. Most of the mixtures are food medicines. The role of honey in more than 90% of formulas is perceived as therapeutic. The ecological distribution of taxa and the cultural aspects of mixtures are discussed, particularly the European and American influences that have shaped the character of multispecies medicinal recipes. PMID- 22315634 TI - Bilateral lung abscesses in a 9-month-old healthy infant. AB - Multiple lung abscesses are extremely rare in healthy children. We report a case of polymicrobial bilateral lung abscess in a 9-month-old previously well infant presenting with a short history of fever and respiratory distress. The management options and outcome are discussed. PMID- 22315633 TI - Effects of acupuncture on Th1, th2 cytokines in rats of implantation failure. AB - The aim is to explore the effect of acupuncture on Th1, Th2 cytokines in rats of implantation failure. Early pregnant rats were randomized into normal group (N), implantation failure group (M), acupuncture group (A), progestin group (H). The model was established with mifepristone. Samples of serum, endometrium were collected on Day 5, 6 and 8 of pregnancy. Compared with group M, the number of embryos was significantly higher in groups N, A and H; IL-1beta, IL-2 protein in serum and endometrium were significantly lower in groups N, A and H, while IL-4, IL-10 were significantly higher in groups N, A and H; the endometrial IL-2, IL-4 mRNA were significantly lower in groups N, A and H, while IL-1beta, IL-10 mRNA were significantly higher in groups N, A and H. Acupuncture could improve the poor receptive state of endometrium due to mifepristone by promoting Th2 cytokines secretion and inhibiting Th1 cytokines to improve blastocyst implantation. PMID- 22315635 TI - Rapid resolution of diffusion weighted MRI abnormality in a patient with a stuttering stroke. AB - We report the unusually rapid and spontaneous normalisation of low diffusivity that accompanied resolution of acute neurological deficits in a stroke patient who underwent two magnetic resonance imaging examinations within 24 h of symptom onset. Diffusion weighted imaging obtained within hours of onset of left sided weakness demonstrated a focal right capsular area of low diffusivity that resolved within 24 h, coinciding with resolution of the patient's symptoms. PMID- 22315636 TI - Preoperative surgical marking: a case of seeing double. AB - Preoperative marking is an integral part of the care of patients undergoing surgical procedures. It occurs on a daily basis in hospitals and involves all members of the healthcare staff and the patient. Incorrect marking or errors can lead to devastating consequences for the patient and staff involved. We present an unusual case of seeing double arrows on a patient undergoing emergency orthopaedic surgery, despite standard preoperative marking procedures. This was recognised in the anaesthetic room and the correct site was confirmed. We aim to highlight this specific problem and remind all involved in preoperative marking of the dangers of a mirror imprint, thereby avoiding seeing double in the anaesthetic or operating room. PMID- 22315637 TI - Benign coital headache relieved by partner's pregnancies with implications for future treatment. AB - This is a case of a male patient with a 27 year history of severe benign coital headache and associated symptoms. His condition was spontaneously relieved in the first trimester of his partner's pregnancy. This relief continued through the remainder of the pregnancy term, returning only after the birth of their child. The timing of the condition's relief and return of symptoms suggested progesterone was an intrinsic factor in this. Post-pregnancy the patient was able to prevent his attacks by taking oral norethisterone 5 mg. While writing this case the patient's partner became pregnant once more, resulting again in spontaneous relief of the patient's syndrome. PMID- 22315638 TI - Immunohistochemical analysis of a merkeloma observed in a patient affected by hereditary haemorrhagic telangiectasia. AB - Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterised by epistaxis, telangiectases, and multiorgan vascular dysplasia. Mutations of the ENG and ACVRL1 genes cause at least 80% of cases. We report the first case of merkeloma found in a patient with HHT carrying an ENG mutation. We analysed the tumour with immunohistochemical methods using primary antibodies against CD105 (endoglin), TGF-beta, Smad4, CD31 and CD34. Tumour cells were positive for Smad4, weakly positive for TGF-beta, and negative for CD105. Vasal endothelial cells were highly positive for CD105, CD31 and CD34. No remarkable differences between cancer and normal cells in our patient or between the patient's merkeloma and two control merkelomas were observed. The presence of a merkeloma in an HHT patient could be an occasional association, but to certainly assume it further investigations are needed. PMID- 22315639 TI - Visual loss from hyphema following intravitreal bevacizumab. AB - Intravitreal injections are the most common ocular procedures in an ophthalmic practice. Despite their safety profiles, complications can happen such as visually threatening intraocular bleeding. We present a case of a 32-year-old woman with idiopathic retinal vasculitis (Eales' disease), rubeosis iridis, and visual loss in the left eye from cystoid macular oedema. The patient had prior vitrectomy and multiple subtenon injections of corticosteroids. She underwent injection of intravitreal bevacizumab. The patient rubbed her eyes and developed subtotal hyphema. She also subsequently developed a panic attack. The bleeding spontaneously resolved over several hours. In eyes needing intraocular injections, caution needs to be taken in patients with rubeosis iridis who have had prior vitrectomy and subtenon injections of corticosteroids, and they need to be instructed to avoid ocular rubbing. PMID- 22315640 TI - Incontinence and mood disorder: is there an association? AB - A variety of psychiatric disorders including depression have been reported in patients suffering from incontinence. It is uncertain if the association between incontinence and depression is causal or is related to a third common factor. We report the case of a 48-year-old man who presented with incontinence of urine and faeces along with a severe depressive episode. No organic cause could be identified for the incontinence. The depressive symptoms as well as the incontinence resolved with treatment with reboxetine and aripiprazole. However, the patient developed a manic episode. This case supports the hypothesis that incontinence and depression may share a common pathogenesis. The authors review the literature to investigate this linkage. The combination of aripiprazole and reboxetine should be used cautiously when treating first episode depression as it can induce a manic switch. Previous reports of manic switch with aripiprazole and reboxetine are reviewed. PMID- 22315641 TI - Primary hyperparathyroidism with unilateral proptosis. PMID- 22315642 TI - Mark of scrub typhus. PMID- 22315643 TI - An aromatic mystery. AB - A case of antiepileptic hypersensitivity syndrome presenting as an acute septic illness is reported. A 67-year-old man, with a history of essential hypertension (treated with amlodipine) and recently diagnosed nocturnal epilepsy (treated with phenytoin), presented initially with an acute pneumonic illness with periorbital oedema. This was treated successfully with antibiotics and his phenytoin was changed to carbamazepine due to concerns regarding the periorbital oedema. He was re-admitted the following month with a history of weight loss, rigors, night sweats and high temperatures. Investigations revealed very high inflammatory markers. Despite extensive tests, no source of infection, autoimmune disease or malignancy was identified. The carbamazepine was then stopped and over the next 5 days the patient's symptoms gradually resolved. The patient's haematological and biochemical abnormalities returned to normal and he was discharged home. Since discharge he has been very well with no further sequelae. PMID- 22315644 TI - Mother tongue lost while second language intact: insights into aphasia. AB - Cortical representations of the native language and a second language may have different anatomical distribution. The relationships between the phonologic and orthographic forms of words continue to be debated. We present a bilingual patient whose competence in his mother tongue was disrupted following brain ischaemia. Semantic units were accessible only as isolated letters in written as well as oral language presentation. His second language appeared completely unaffected. Whole word system disturbance of both orthography and phonology pathways of the native language could explain this presentation. It is a great opportunity to learn about the language neural network when a bilingual subject presents with brain ischaemia. PMID- 22315645 TI - Abdominal wall abscess: more than meets the eye. AB - An 83-year-old, mildly demented rest home resident presented to the emergency department with a 2 day history of a right sided abdominal wall mass. He had a mechanical fall 2 days previously and landed on his right side and had attributed the mass to this. He had no symptoms apart from feeling bloated and not being able to pass wind for a day. He had passed a normal bowel motion the day before presentation. On abdominal examination there was an 11 * 4 cm mass in the right lower quadrant. It was firm in consistency, non-fluctuant and non-tender to touch. There was mild erythema over the area but no skin breaks. Chest radiograph was unremarkable. The abdominal film showed dilated small bowel and no large bowel could be seen. A computed tomography (CT) scan showed a thick walled gallbladder with multiple calculi and air present. There was also an extensive air and fluid collection in the layers of the abdominal wall and subcutaneous fat which arose from a perforation of the gallbladder. The patient was not a surgical candidate due to multiple comorbidities. The patient was treated with antibiotics and underwent a CT guided percutaneous cholecystostomy. Despite the radiological intervention and antibiotics the patient progressively deteriorated and died peacefully 5 days after admission. PMID- 22315646 TI - Extraskeletal myxoid chondrosarcoma: a case report of complete remission by chemotherapy and review of the literature. AB - Extraskeletal myxoid chondrosarcoma is a rare soft tissue sarcoma. Surgery is the cornerstone of the management of this tumour. The response rate to chemotherapy has been very poor; with the exception of one reported case which showed promising results, overall results are disappointing because no significant radiologic or clinical responses have been noted with chemotherapy. Here we report the case of a 15-year-old girl who presented with extraskeletal myxoid chondrosarcoma in the sacrococcygeal region which was regarded as unresectable. After four cycles of chemotherapy the mass showed complete remission which has lasted >6 months. PMID- 22315647 TI - Increasing thigh pain: acute compartment syndrome! PMID- 22315648 TI - Congenital hyperinsulinism with hyperammonaemia. AB - Congenital hyperinsulinism is considered to be the most frequent cause of persistent recurrent hypoglycaemia in infants. The clinical presentation and response to pharmacological treatment may vary significantly depending on the underlying pathology. We report a case of a female infant with mild but early onset of recurrent hypoglycaemia. Metabolic workup revealed hyperinsulinism combined with mild hyperammonaemia as well as elevation of alpha-ketoglutarate in urine. Genetic testing demonstrated a de novo mutation in exon 7 of the glutamate dehydrogenase gene on chromosome 10. Episodes of hypoglycaemia responded to treatment with diazoxide. The differential diagnosis, pathophysiology and treatment of congenital hyperinsulinism is discussed. PMID- 22315649 TI - Dolichoectasia and multifocal simultaneous intracranial haemorrhages. AB - Dolichoectasia is found primarily in aged individual with atherosclerotic disease. It presents with brain stem compression and stroke, which could be ischaemic or haemorrhagic. Even if severe atherosclerosis is thought to play a pivotal role, new evidence suggest that the internal elastic laminae is disrupted, intracranially and extracranially, so multiorganic involvement with various clinical presentations can occur. We present a rare association of multiorganic dolichoectasia debuting with multiple intracranial haemorrhages. A 79-year-old woman presented with altered mental status and left hemiplegia. The work up demonstrated brain arteries dolichoectasia and an abdominal aortic aneurysm with multiple site intraparenchymal haemorrhages. In this case, the presentation of multiple site dolichoectasia and multiple haemorrhages is probably linked to a systemic "media disease" that affected the media of small, medium and large arteries rather than a coincidental finding. PMID- 22315650 TI - A meta-analysis of the short- and long-term results of randomized controlled trials that compared laparoscopy-assisted and open colectomy for colon cancer. AB - PURPOSE: We conducted a meta-analysis to evaluate and compare the short- and long term results of laparoscopy-assisted colectomy (LAC) and open colectomy (OC) for colon cancer. METHODS: We searched MEDLINE, EMBASE, Science Citation Index, and Cochrane Controlled Trial Register for relevant papers published between January 1990 and October 2011 by using the search terms "laparoscopy," "laparoscopy assisted," "surgery," "colectomy," "colon cancer," and "randomized clinical trials (RCTs)". We analyzed the outcomes of each type of surgery over short- and long-term periods. RESULTS: We selected 12 papers reporting RCTs that compared LAC with OC for colon cancer. Our meta-analysis included 4614 patients with colon cancer; of these, 2444 had undergone LAC and 2170 had undergone OC. In the short term period, we found that the rates of overall postoperative complications and ileus in LAC were lower than in OC groups. LAC was associated with a reduction in intraoperative blood loss, a shorter duration of time to resumption and hospital stay, and lower rates of overall complication and ileus over the short-term, but with similar long-term oncologic outcomes such as overall and cancer-related mortality, overall recurrence, local recurrence, distant metastasis, and wound site recurrence, compared to OC. CONCLUSIONS: It is suggested that LAC may be preferred to OC for colon cancer. PMID- 22315651 TI - Molecular Characterization of a Patient's Small Cell Carcinoma of the Ovary of the Hypercalcemic Type. AB - Small cell carcinoma of the ovary of the hypercalcemic type (SCCOHT) is a very rare tumor type that mainly affects young women. We report a 21-year old woman with SCCOHT. The patient initially presented with stage T3AN1MX disease and treated with surgery. The patient then received 8 cycles of multi-agent chemotherapy including cisplatin, bleomycin, cyclophosphamide, doxorubicin, and etoposide. Upon relapse, the patient underwent total abdominal hysterectomy, followed by chemotherapy with gemcitabine. The patient subsequently received radiation therapy and chemotherapy with bevacizumab, irinotecan and docetaxel. She passed away approximately 5 months after the second surgery and with her prior permission an immediate autopsy was performed. We examined the gene expression and copy number profiles of the tumor tissue samples obtained from the autopsy and compared them to normal ovary tissues. Our results indicated that although this tumor did not harbor chromosomal abnormalities nor gene copy number changes, there were significant gene expression changes in a number of genes/pathways. More than 5,000 genes showed significant differential expression in the tumor when compared to normal ovary tissue. Pathway enrichment analysis further identified several pathways/processes including the Vitamin D receptor signaling and the hedgehog signaling pathways to be significantly dysregulated. The gene expression profiling also suggests a number of agents such as pazopanib, bortezomib, 5-azacytidine, and PARP inhibitors as treatment options to possibly explore in future trials against this disease. PMID- 22315652 TI - Telomerase-independent paths to immortality in predictable cancer subtypes. AB - The vast majority of cancers commandeer the activity of telomerase - the remarkable enzyme responsible for prolonging cellular lifespan by maintaining the length of telomeres at the ends of chromosomes. Telomerase is only normally active in embryonic and highly proliferative somatic cells. Thus, targeting telomerase is an attractive anti-cancer therapeutic rationale currently under investigation in various phases of clinical development. However, previous reports suggest that an average of 10-15% of all cancers lose the functional activity of telomerase and most of these turn to an Alternative Lengthening of Telomeres pathway (ALT). ALT-positive tumours will therefore not respond to anti telomerase therapies and there is a real possibility that such drugs would be toxic to normal telomerase-utilising cells and ultimately select for resistant cells that activate an ALT mechanism. ALT exploits certain DNA damage response (DDR) components to counteract telomere shortening and rapid trimming. ALT has been reported in many cancer subtypes including sarcoma, gastric carcinoma, central nervous system malignancies, subtypes of kidney (Wilm's Tumour) and bladder carcinoma, mesothelioma, malignant melanoma and germ cell testicular cancers to name but a few. A recent heroic study that analysed ALT in over six thousand tumour samples supports this historical spread, although only reporting an approximate 4% prevalence. This review highlights the various methods of ALT detection, unravels several molecular ALT models thought to promote telomere maintenance and elongation, spotlights the DDR components known to facilitate these and explores why certain tissues are more likely to subvert DDR away from its usually protective functions, resulting in a predictive pattern of prevalence in specific cancer subsets. PMID- 22315653 TI - A new approach to the molecular analysis of docking, priming, and regulated membrane fusion. AB - Studies using isolated sea urchin cortical vesicles have proven invaluable in dissecting mechanisms of Ca(2+)-triggered membrane fusion. However, only acute molecular manipulations are possible in vitro. Here, using selective pharmacological manipulations of sea urchin eggs ex vivo, we test the hypothesis that specific lipidic components of the membrane matrix selectively affect defined late stages of exocytosis, particularly the Ca(2+)-triggered steps of fast membrane fusion. Egg treatments with cholesterol-lowering drugs resulted in the inhibition of vesicle fusion. Exogenous cholesterol recovered fusion extent and efficiency in cholesterol-depleted membranes; alpha-tocopherol, a structurally dissimilar curvature analogue, selectively restored fusion extent. Inhibition of phospholipase C reduced vesicle phosphatidylethanolamine and suppressed both the extent and kinetics of fusion. Although phosphatidylinositol 3-kinase inhibition altered levels of polyphosphoinositide species and reduced all fusion parameters, sequestering polyphosphoinositides selectively inhibited fusion kinetics. Thus, cholesterol and phosphatidylethanolamine play direct roles in the fusion pathway, contributing negative curvature. Cholesterol also organizes the physiological fusion site, defining fusion efficiency. A selective influence of phosphatidylethanolamine on fusion kinetics sheds light on the local microdomain structure at the site of docking/fusion. Polyphosphoinositides have modulatory upstream roles in priming: alterations in specific polyphosphoinositides likely represent the terminal priming steps defining fully docked, release-ready vesicles. Thus, this pharmacological approach has the potential to be a robust high-throughput platform to identify molecular components of the physiological fusion machine critical to docking, priming, and triggered fusion. PMID- 22315654 TI - Honey supplementation in spontaneously hypertensive rats elicits antihypertensive effect via amelioration of renal oxidative stress. AB - Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR). It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY) rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA) levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione S-transferase (GST) were significantly downregulated while total antioxidant status (TAS) and activities of GST and catalase (CAT) were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR. PMID- 22315655 TI - Gliclazide does not fully prevent 2-deoxy-D-ribose-induced oxidative damage because it does not restore glutathione content in a pancreatic beta-cell line. AB - We compared the effects of gliclazide, an antidiabetic agent with antioxidant properties, and N-acetyl-L-cysteine (NAC), a glutathione precursor, in protecting against 2-deoxy-D-ribose- (dRib-) induced oxidative damage in HIT-T15 cells. Using trypan blue staining and flow cytometry with annexin V/PI staining, gliclazide treatment slightly reversed dRib-induced cell death and apoptosis, and NAC treatment markedly reduced both measures. Likewise, flow cytometry using DHR 123 staining showed that the levels of dRib-induced reactive oxygen species (ROS) were partially suppressed by gliclazide and completely inhibited by NAC. Using electron spin resonance spectrometry, gliclazide and NAC scavenged hydroxyl radicals generated by Fenton reaction to a similar degree in a cell-free system. NAC, but not gliclazide, completely restored the intracellular glutathione depleted by dRib using monochlorobimane fluorescence and glutathione assays. Thus, gliclazide treatment suppressed dRib-induced oxidative damage in HIT-T15 cells less than NAC did because gliclazide did not restore the intracellular glutathione content as effectively as NAC. In addition, the elevation of intracellular glutathione rather than free radical scavenging might be an important mechanism for protecting against dRib-induced oxidative damage in a beta-cell line. PMID- 22315657 TI - Creatinine-based estimations of kidney function are unreliable in obese kidney donors. AB - Accurate assessment of kidney function by measurement of glomerular filtration rate (GFR) is essential to the risk assessment of prospective living kidney donors. We evaluated the performance of various estimating equations for creatinine clearance (Cockcroft-Gault), GFR (Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration), and 24-hour urine collections for creatinine clearance in obese potential kidney donors. We evaluated 164 potential kidney donors including 49 with a BMI of 30-35 and 32 with a BMI >35 that have completed a routine living donor evaluation with a measured GFR. All the estimating equations performed poorly in obese donors. While 24-hour urine collections performed better, only 15% had an adequate 24 hour urine collection. Since obese kidney donors may be at higher than average risk for kidney failure, accurate assessment of kidney function in these donors is crucial to ensure their long-term health postdonation. PMID- 22315656 TI - NF-kappaB and matrix-dependent regulation of osteopontin promoter activity in allylamine-activated vascular smooth muscle cells. AB - Repeated cycles of oxidative injury by allylamine in vivo induce a proliferative rat vascular (aortic) smooth muscle cell (vSMC) phenotype characterized by matrix dependent enhancement of mitogenic sensitivity, changes in cell surface integrin expression, and osteopontin (opn) overexpression. Here, we show that constitutive and mitogen-stimulated NF-kappaB DNA binding activity is enhanced in allylamine vSMCs. Matrix-specific changes in cellular Rel protein expression were observed in allylamine vSMCs. The NF-kappaB DNA binding element located at -1943 in the 5' UTR strongly inhibited opn promoter activity in allylamine vSMCs, and this response was regulated by the extracellular matrix. Constitutive increases in opn promoter activity were only seen when allylamine cells were seeded on a fibronectin substrate, and this response was independent of the NF-kappaB DNA binding sequence within the regulatory region. Thus, NF-kappaB functions as a critical regulator of the allylamine-induced proliferative phenotype in vSMCs. PMID- 22315658 TI - Sirolimus enhances cyclosporine a-induced cytotoxicity in human renal glomerular mesangial cells. AB - End Stage Renal Disease (ESRD) is an ever increasing problem worldwide. However the mechanisms underlying disease progression are not fully elucidated. This work addressed nephrotoxicity induced by the immunosuppressive agents' cyclosporine A (CsA) and sirolimus (SRL). Nephrotoxicity is the major limiting factor in long term use of CsA. SRL causes less nephrotoxicity than CsA. Therefore investigations into the differential effects of these agents may identify potential mechanisms of nephrotoxicity and means to prevent ESRD induced by therapeutic drugs. Using ELISA, Western blotting, quantitative PCR and a reporter gene assay we detailed the differential effects of CsA and SRL in human renal mesangial cells. CsA treatment increased profibrotic TGF-beta1 secretion in human mesangial cells whereas SRL did not, indicating a role for TGF-beta in CsA toxicity. However we observed a synergistic nephrotoxic effect when CsA and SRL were co-administered. These synergistic alterations may have been due to an increase in CTGF which was not evident when the immunosuppressive drugs were used alone. The CsA/SRL combination therapy significantly enhanced Smad signalling and altered the extracellular matrix regulator matrix metalloproteinase 9 (MMP-9). Inhibition of the ERK 1/2 pathway, attenuated these CsA/SRL induced alterations indicating a potentially significant role for this pathway. PMID- 22315659 TI - B-Cell Response during Protozoan Parasite Infections. AB - In this review, we discuss how protozoan parasites alter immature and mature B cell compartment. B1 and marginal zone (MZ) B cells, considered innate like B cells, are activated during protozoan parasite infections, and they generate short lived plasma cells providing a prompt antibody source. In addition, protozoan infections induce massive B cell response with polyclonal activation that leads to hypergammaglobulnemia with serum antibodies specific for the parasites and self and/or non related antigens. To protect themselves, the parasites have evolved unique ways to evade B cell immune responses inducing apoptosis of MZ and conventional mature B cells. As a consequence of the parasite induced-apoptosis, the early IgM response and an already establish humoral immunity are affected during the protozoan parasite infection. Moreover, some trypanosomatides trigger bone marrow immature B cell apoptosis, influencing the generation of new mature B cells. Simultaneously with their ability to release antibodies, B cells produce cytokines/quemokines that influence the characteristic of cellular immune response and consequently the progression of parasite infections. PMID- 22315660 TI - Comparison of Anterior Chamber Depth Measurements from the Galilei Dual Scheimpflug Analyzer with IOLMaster. AB - Purpose. To compare anterior chamber depth (ACD), representing the distance between the anterior corneal surface and anterior lens surface measurements between the Galilei Dual Scheimpflug Analyzer and the IOLMaster. Methods. A retrospective review of 65 individual patient eyes with normal anterior segments, and no prior ocular surgery was performed. Patients underwent ACD measurements with both devices during the same session by a trained examiner. Interdevice agreement was evaluated using paired two-tailed t-tests, Pearson correlation coefficient, and Bland-Altman analysis. Results. The mean +/- standard deviation (SD) ACD for the Galilei and IOLMaster was 3.37 +/- 0.36 mm (range from 2.62 to 4.13) and 3.25 +/- 0.38 mm (range from 2.34 to 3.92), respectively (Pearson correlation coefficient = 0.96). ACD mean difference was 0.12 mm (P < 0.0001); 95% limits of agreement was from -0.09 to 0.34. The Galilei measured slightly longer ACD values than the IOLMaster. There was no relationship between axial length and interdevice difference. Conclusion. ACD measurements correlate well between the Galilei and IOLMaster, with Galilei values on average 0.12 mm longer than the IOLMaster. PMID- 22315661 TI - Glaucoma and corneal transplant procedures. AB - Glaucoma after corneal transplantation is a leading cause of ocular morbidity after penetrating keratoplasty. The incidence reported is highly variable and a number of etiologic factors have been identified. A number of treatment options are available; surgical intervention for IOP control is associated with a high incidence of graft failure. IOP elevation is less frequently seen following deep anterior lamellar keratoplasty. Descemet's striping-automated endothelial keratoplasty is also associated with postprocedure intraocular pressure elevation and secondary glaucoma and presents unique surgical challenges in patients with preexisting glaucoma surgeries. Glaucoma exists in up to three-quarters of patients who undergo keratoprosthesis surgery and the management if often challenging. The aim of this paper is to highlight the incidence, etiology, and management of glaucoma following different corneal transplant procedures. It also focuses on the challenges in the diagnosis of glaucoma and intraocular pressure monitoring in this group of patients. PMID- 22315662 TI - Development of macular holes after rhegmatogenous retinal detachment repair in Japanese patients. AB - Purpose. To determine the factors associated with the development of a macular hole (MH) after successful rhegmatogenous retinal detachment (RRD) surgery. Methods. Of 1260 eyes that underwent surgery for RRD between April 2005 and March 2010 in our hospital, the medical records of 4 cases from our hospital and one case from another hospital that had undergone RRD surgery and later developed MH were reviewed. This is a retrospective study. Results. 837 eyes underwent pars plana vitrectomy (PPV) with or without scleral buckling (SB), and 423 eyes underwent SB. The four cases that developed MH had PPV alone and one case had PPV with SB. After including the results of three earlier reports, the mean interval for the MH to develop after SB alone was significantly shorter than after PPV alone or after PPV with SB. Conclusions. The SB procedures might accelerate the development of MH after RRD surgery. PMID- 22315663 TI - Comparison of macular thickness in diabetic macular edema using spectral-domain optical coherence tomography and time-domain optical coherence tomography. AB - Purpose. To compare the macular thicknesses in diabetic macular edema (DME) measured with spectral-domain optical coherence tomography (SD-OCT) and time domain (TD) OCT. Patients and Methods. The average macular thicknesses of 50 eyes of 29 patients with DME were measured using SD-OCT and TD-OCT. Results. The mean macular thicknesses measured with TD-OCT and SD-OCT were 401.5 +/- 117.8 MUm (mean +/- SD) and 446.2 +/- 123.5 MUm, respectively. The macular thicknesses measured with the two devices were well correlated (Pearson's product moment correlation, r = 0.977, P < 0.001). A significant correlation was found between the best-corrected visual acuity and the retinal thickness measured by TD-OCT and SD-OCT (Pearson's product moment correlation, TD-OCT, r = 0.34; P < 0.05; SD-OCT, r = 0.32; P < 0.05). Discussion. The mean macular thickness measured with SD-OCT was about 45 MUm thicker than that measured with TD-OCT. Attention should be paid when comparing data obtained using different OCT machines. PMID- 22315664 TI - Role of Flexibility in Protein-DNA-Drug Recognition: The Case of Asp677Gly Val703Ile Topoisomerase Mutant Hypersensitive to Camptothecin. AB - Topoisomerases I are ubiquitous enzymes that control DNA topology within the cell. They are the unique target of the antitumor drug camptothecin that selectively recognizes the DNA-topoisomerase covalent complex and reversibly stabilizes it. The biochemical and structural-dynamical properties of the Asp677Gly-Val703Ile double mutant with enhanced CPT sensitivity have been investigated. The mutant displays a lower religation rate of the DNA substrate when compared to the wild-type protein. Analyses of the structural dynamical properties by molecular dynamics simulation show that the mutant has reduced flexibility and an active site partially destructured at the level of the Lys532 residue. These results demonstrate long-range communication mechanism where reduction of the linker flexibility alters the active site geometry with the consequent lowering of the religation rate and increase in drug sensitivity. PMID- 22315666 TI - Heme induction with delta-aminolevulinic Acid stimulates an increase in water and electrolyte excretion. AB - Purpose. Studies were performed to examine hemodynamic and renal function before and after acute induction of the endogenous CO system with delta-aminolevulinic acid (DALA), which drives HO activity. Methods. In vivo studies were conducted on Inactin-anesthetized male Sprague Dawley rats (250-300 g) either with or without chronic pretreatment with L-NAME (50 mg/Kg, q12 hours x4d). Results. DALA (80 MUmol/Kg, IV bolus) administration acutely increased endogenous CO production and HO-1 protein. In untreated and L-NAME-pretreated rats, DALA did not alter BP, GFR, or RBF but increased UF, U(Na)V, and U(K)V (untreated: Delta108.8 +/- 0.28%, 172.1 +/- 18.4%, and 165.2 +/- 45.9%; pretreated: Delta109.4 +/- 0.29%, 187.3 +/- 26.9%, and 197.2 +/- 45.7%). Acute administration of biliverdin (20 mg/kg, IV) and bilirubin (30 mg/kg, IV) to similarly treated animals did not alter UF, U(Na)V, and U(K)V. Conclusion. These results demonstrate that heme oxygenase induction increases urine and electrolyte excretion and suggest a direct tubular action of endogenous carbon monoxide. PMID- 22315665 TI - Protective Role of the ACE2/Ang-(1-9) Axis in Cardiovascular Remodeling. AB - Despite reduction in cardiovascular (CV) events and end-organ damage with the current pharmacologic strategies, CV disease remains the primary cause of death in the world. Pharmacological therapies based on the renin angiotensin system (RAS) blockade are used extensively for the treatment of hypertension, heart failure, and CV remodeling but in spite of their success the prevalence of end organ damage and residual risk remain still high. Novel approaches must be discovered for a more effective treatment of residual CV remodeling and risk. The ACE2/Ang-(1-9) axis is a new and important target to counterbalance the vasoconstrictive/proliferative RAS axis. Ang-(1-9) is hydrolyzed slower than Ang (1-7) and is able to bind the Ang II type 2 receptor. We review here the current experimental evidence suggesting that activation of the ACE2/Ang-(1-9) axis protects the heart and vessels (and possibly the kidney) from adverse cardiovascular remodeling in hypertension as well as in heart failure. PMID- 22315667 TI - From rat to human: regulation of Renin-Angiotensin system genes by sry. AB - The testis determining protein, Sry, has functions outside of testis determination. Multiple Sry loci are found on the Y-chromosome. Proteins from these loci have differential activity on promoters of renin-angiotensin system genes, possibly contributing to elevation of blood pressure. Variation at amino acid 76 accounts for the majority of differential effects by rat proteins Sry1 and Sry3. Human SRY regulated rat promoters in the same manner as rat Sry, elevating Agt, Ren, and Ace promoter activity while downregulating Ace 2. Human SRY significantly regulated human promoters of AGT, REN, ACE2, AT2, and MAS compared to control levels, elevating AGT and REN promoter activity while decreasing ACE2, AT2, and MAS. While the effect of human SRY on individual genes is often modest, we show that many different genes participating in the renin angiotensin system can be affected by SRY, apparently in coordinated fashion, to produce more Ang II and less Ang-(1-7). PMID- 22315668 TI - Study on the dynamics of cortisol secretions in hypertensive elderly patients. AB - Ageing is defined as a slow, irreversible process of cellular changes, that are due to a lack of balance between degradation and repair, a continuous interaction between physiological and pathological processes. Physiological aspects in elderly people are often confused with disease. Given these general considerations, we would make observations about the dynamics of cortisol secretion in healthy elderly subjects and patients with a diagnosed cardiovascular disease, more precisely hypertension. The study was conducted during 2003-2010, on a number of 135 patients older than 65 years of age, who were divided into two groups: one group counting 66 patients and consisting of healthy elderly controls (without systemic disease, renal, endocrine, or cardiovascular known issues) and group 2 who consists of 69 elderly patients who associate known hypertensive and other cardiovascular issues. PMID- 22315669 TI - Decreased Cognitive/CNS Function in Young Adults at Risk for Hypertension: Effects of Sleep Deprivation. AB - Hypertension has been linked to impaired cognitive/CNS function, and some of these changes may precede development of frank essential hypertension. The stress and fatigue of sleep deprivation may exacerbate these cognitive changes in young adults at risk. We hypothesize that individuals at risk for hypertension will show significant declines in cognitive function during a night of sleep deprivation. Fifty-one young adults were recruited for 28-hour total sleep deprivation studies. Hypertension risk was assessed by mildly elevated resting blood pressure and by family history of hypertension. A series of cognitive memory tasks was given at four test sessions across the sleep deprivation period. Although initially comparable in cognitive performance, persons at risk showed larger declines across the night for several indices of working memory, including code substitution, category, and order recall. These results suggest that cognitive/CNS changes may parallel or precede blood pressure dysregulation in the early stages of hypertension development. The role of CNS changes in the etiology of essential hypertension is discussed. PMID- 22315670 TI - Optimal Conditions for Continuous Immobilization of Pseudozyma hubeiensis (Strain HB85A) Lipase by Adsorption in a Packed-Bed Reactor by Response Surface Methodology. AB - This study aimed to develop an optimal continuous process for lipase immobilization in a bed reactor in order to investigate the possibility of large scale production. An extracellular lipase of Pseudozyma hubeiensis (strain HB85A) was immobilized by adsorption onto a polystyrene-divinylbenzene support. Furthermore, response surface methodology (RSM) was employed to optimize enzyme immobilization and evaluate the optimum temperature and pH for free and immobilized enzyme. The optimal immobilization conditions observed were 150 min incubation time, pH 4.76, and an enzyme/support ratio of 1282 U/g support. Optimal activity temperature for free and immobilized enzyme was found to be 68 degrees C and 52 degrees C, respectively. Optimal activity pH for free and immobilized lipase was pH 4.6 and 6.0, respectively. Lipase immobilization resulted in improved enzyme stability in the presence of nonionic detergents, at high temperatures, at acidic and neutral pH, and at high concentrations of organic solvents such as 2-propanol, methanol, and acetone. PMID- 22315671 TI - A simpler method for predicting weight loss in the first year after Roux-en-Y gastric bypass. AB - Factors postulated to predict weight loss after gastric bypass surgery, include race, age, gender, technique, height, and initial weight. This paper contained 1551 gastric bypass patients (85.9% female). Operations were performed by one surgeon (MLO) at community hospitals in Southern California from 1989 to 2008 with 314 being laparoscopic and 1237 open. We created the following equation: In[percent weight] = At(2) - Bt, where t was the time after operation (days) and A and B are constants. Analysis was completed on R-software. The model fits with R(2) value 0.93 and gives patients a realistic mean target weight with a confidence interval of 95% for the first year. Conclusion. We created a curve predicting weight loss after surgery as a percentage of initial weight. Initial weight was the single most important predictor of weight loss after surgery. Other recorded variables accounted for less than 1% of variability. Unknown factors account for the remaining 6-7%. PMID- 22315672 TI - Is the gut microbiota a new factor contributing to obesity and its metabolic disorders? AB - The gut microbiota refers to the trillions of microorganisms residing in the intestine and is integral in multiple physiological processes of the host. Recent research has shown that gut bacteria play a role in metabolic disorders such as obesity, diabetes, and cardiovascular diseases. The mechanisms by which the gut microbiota affects metabolic diseases are by two major routes: (1) the innate immune response to the structural components of bacteria (e.g., lipopolysaccharide) resulting in inflammation and (2) bacterial metabolites of dietary compounds (e.g., SCFA from fiber), which have biological activities that regulate host functions. Gut microbiota has evolved with humans as a mutualistic partner, but dysbiosis in a form of altered gut metagenome and collected microbial activities, in combination with classic genetic and environmental factors, may promote the development of metabolic disorders. This paper reviews the available literature about the gut microbiota and aforementioned metabolic disorders and reveals the gaps in knowledge for future study. PMID- 22315673 TI - The Prevalence of Physical Activity and Sedentary Behaviours Relative to Obesity among Adolescents from Al-Ahsa, Saudi Arabia: Rural versus Urban Variations. AB - Purpose. The aims of this study were to explore the lifestyle of young people living in Al-Ahsa Governorate; to investigate differences due to gender, age, school type, and geographical location. Methods. 1270 volunteered youth (15-19 years) completed a self-report questionnaire that contained 47 items relating to patterns of physical activity (PA), sedentary activity, and eating habits. The questionnaire allows the calculation of total energy expenditure in metabolic equivalent (MET-min) values per week. Results. Significant differences in the PA levels of youth were evident with regard to gender, geographical areas, and type of school. Also, normal weight males reported the highest levels of PA compared to overweight and obese. Conclusions. Youth living in rural desert were less physically active than those living in urban or rural farm environments. Youth of "normal" weight were more active than obese. Males were more active than females and PA levels appeared to decline with age. PMID- 22315674 TI - Accelerated growth rate induced by neonatal high-protein milk formula is not supported by increased tissue protein synthesis in low-birth-weight piglets. AB - Low-birth-weight neonates are routinely fed a high-protein formula to promote catch-up growth and antibiotics are usually associated to prevent infection. Yet the effects of such practices on tissue protein metabolism are unknown. Baby pigs were fed from age 2 to 7 or 28 d with high protein formula with or without amoxicillin supplementation, in parallel with normal protein formula, to determine tissue protein metabolism modifications. Feeding high protein formula increased growth rate between 2 and 28 days of age when antibiotic was administered early in the first week of life. This could be explained by the occurrence of diarrhea when piglets were fed the high protein formula alone. Higher growth rate was associated with higher feed conversion and reduced protein synthesis rate in the small intestine, muscle and carcass, whereas proteolytic enzyme activities measured in these tissues were unchanged. In conclusion, accelerated growth rate caused by high protein formula and antibiotics was not supported by increased protein synthesis in muscle and carcass. PMID- 22315675 TI - Dietary Recommendations for the Prevention of Type 2 diabetes: What Are They Based on? AB - Introduction. Type 2 diabetes is increasing in all populations and all age groups across the world. Areas undergoing rapid westernisation and rapid nutrition transition are seeing the greatest increases in prevalence suggesting that environmental factors are important. Studies from around the world have shown that dietary modification for the prevention of T2DM can be successful; however which dietary factors are important remains to be fully elucidated. The WHO, ADA, and Diabetes UK have developed guidelines for the prevention of T2DM even though the WHO states that data from lifestyle modification programmes does not allow for the disentanglement of dietary factors. Aim of Review. The aim of this focused review is to evaluate the current dietary recommendations for the prevention of T2DM. In addition we aim to explore the available evidence from both observation studies and clinical trials to determine whether these recommendations are appropriate. PMID- 22315676 TI - Food Store Environment Modifies Intervention Effect on Fruit and Vegetable Intake among Low-Income Women in North Carolina. AB - Background. The aim of the study is to determine how the food store environment modifies the effects of an intervention on diet among low-income women. Study Design. A 16-week face-to-face behavioral weight loss intervention was delivered among low income midlife women. Methods. The retail food environment for all women was characterized by (1) the number and type of food stores within census tracts; (2) availability of healthy foods in stores where participants shop; (3) an aggregate score of self-reported availability of healthy foods in neighborhood and food stores. Statistical Analyses. Multivariable linear regression was used to model the food store environment as an effect modifier between the intervention effect of fruit and vegetable serving change. Results. Among intervention participants with a low perception of availability of healthy foods in stores, the intervention effect on fruit and vegetable serving change was greater [1.89, 95% CI (0.48, 3.31)] compared to controls. Among intervention participants residing in neighborhoods with few super markets, the intervention effect on fruit and vegetable serving change was greater [1.62, 95% CI (1.27, 1.96)] compared to controls. Conclusion. Results point to how the food store environment may modify the success of an intervention on diet change among low income women. PMID- 22315677 TI - Changes in Lipids and Lipoproteins after Selective LDL Apheresis (7-Year Experience). AB - Background. The aim of the study was to investigate the changes in plasma lipids and lipoproteins and the cardiovascular events after selective LDL apheresis. Methods and Results. Two pediatric patients with familial hypercholesterolemia aged 11 and 13 years and 19 dyslipidemic adults aged 41 +/- 14 years underwent direct adsorption of lipoproteins (DALI) sessions. The mean follow-up period was 47 +/- 23 months. The total cholesterol (TC) values before and after treatment were 8.2 +/- 2.2 and 3.1 +/- 1.6 mmol/l (318 +/- 86 and 122 +/- 62 mg/dL), respectively. The interval mean of TC was 6.9 +/- 1.9 mmol/l (268 +/- 75 mg/dL). The LDL cholesterol concentrations before and after treatment were 6.6 +/- 2.1 and 1.7 +/- 1.1 mmol/l, (256 +/- 82 mg/dL and 65 +/- 41 mg/dL), respectively. The percentage of acute LDL cholesterol reduction was 75 +/- 11%. Cardiovascular events were observed in seven patients. The average annual event rate was 5.51%. Conclusion. LDL apheresis is a very important therapeutic tool in managing patients at high risk for premature CAD or with aggressive CAD, despite adequate medical treatment. PMID- 22315678 TI - Current End-of-Life Care Needs and Care Practices in Acute Care Hospitals. AB - A descriptive-comparative study was undertaken to examine current end-of-life care needs and practices in hospital. A chart review for all 1,018 persons who died from August 1, 2008 through July 31, 2009 in two full-service Canadian hospitals was conducted. Most decedents were elderly (73.8%) and urbanite (79.5%), and cancer was the most common diagnosis (36.2%). Only 13.8% had CPR performed at some point during this hospitalization and 8.8% had CPR immediately preceding death, with 87.5% having a DNR order and 30.8% providing an advance directive. Most (97.3%) had one or more life-sustaining technologies in use at the time of death. These figures indicate, when compared to those in a similar mid-1990s Canadian study, that impending death is more often openly recognized and addressed. Technologies continue to be routinely but controversially used. The increased rate of end-stage CPR from 2.9% to 8.8% could reflect a 1994+ shift of expected deaths out of hospital. PMID- 22315679 TI - Toothbrush contamination: a review of the literature. AB - Toothbrushes are commonly used in hospital settings and may harbor potentially harmful microorganisms. A peer-reviewed literature review was conducted to evaluate the cumulative state of knowledge related to toothbrush contamination and its possible role in disease transmission. A systematic review was conducted on adult human subjects through three distinct searches. The review resulted in seven experimental and three descriptive studies which identified multiple concepts related to toothbrush contamination to include contamination, methods for decontamination, storage, design, and environmental factors. The selected studies found that toothbrushes of healthy and oral diseased adults become contaminated with pathogenic bacteria from the dental plaque, design, environment, or a combination of factors. There are no studies that specifically examine toothbrush contamination and the role of environmental factors, toothbrush contamination, and vulnerable populations in the hospital setting (e.g., critically ill adults) and toothbrush use in nursing clinical practice. PMID- 22315680 TI - Evaluating the Role of Compression Stockings in Preventing Post thrombotic Syndrome: A Review of the Literature. AB - Background. Postthrombotic syndrome (PTS) is a burdensome and costly complication of deep vein thrombosis (DVT). Up to 50% of patients with DVT will develop the disease within two years following the diagnosis of acute DVT. Various risk factors for developing PTS have been identified and different modalities have been used to prevent its development. Compression stockings have been studied for the prevention of PTS in patients diagnosed with proximal DVT. Methods. MEDLINE and EMBASE databases were searched to identify relevant original articles. Results. Several trials including two metaanalyses have examined the role of compression stockings for the prevention of PTS. Although most trials showed significant reduction in the development of PTS with the use of compression stockings, limitations in study design prevent the generalizability of the data. Two studies supported an individualized tailored duration especially in patients at low risk for developing the syndrome. A randomized double-blind placebo controlled trial involving 800 patients is currently ongoing and may confirm the results of older studies. Conclusions. Clinical trials support the use of compression stockings in patients diagnosed with proximal DVT for the prevention of PTS. PMID- 22315681 TI - Peripheral galanin receptor 2 as a target for the modulation of pain. AB - The neuropeptide galanin is widely expressed in the nervous system and has an important role in nociception. It has been shown that galanin can facilitate and inhibit nociception in a dose-dependent manner, principally through the central nervous system, with enhanced antinociceptive actions after nerve injury. However, following nerve injury, expression of galanin within the peripheral nervous system is dramatically increased up to 120-fold. Despite this striking increase in the peripheral nervous system, few studies have investigated the role that galanin plays in modulating nociception at the primary afferent nociceptor. Here, we summarise the recent work supporting the role of peripherally expressed galanin with particular reference to the dual actions of the galanin receptor 2 in neuropathic pain highlighting this as a potential target analgesic. PMID- 22315683 TI - Role of New Functional MRI Techniques in the Diagnosis, Staging, and Followup of Gynecological Cancer: Comparison with PET-CT. AB - Recent developments in diagnostic imaging techniques have magnified the role and potential of both MRI and PET-CT in female pelvic imaging. This article reviews the techniques and clinical applications of new functional MRI (fMRI) including diffusion-weighted MRI (DWI), dynamic contrast-enhanced (DCE)-MRI, comparing with PET-CT. These new emerging provide not only anatomic but also functional imaging, allowing detection of small volumes of active tumor at diagnosis and early disease relapse, which may not result in detectable morphological changes at conventional imaging. This information is useful in distinguishing between recurrent/residual tumor and post-treatment changes and assessing treatment response, with a clear impact on patient management. Both PET-CT and now fMRI have proved to be very valuable tools for evaluation of gynecologic tumors. Most papers try to compare these techniques, but in our experience both are complementary in management of these patients. Meanwhile PET-CT is superior in diagnosis of ganglionar disease; fMRI presents higher accuracy in local preoperative staging. Both techniques can be used as biomarkers of tumor response and present high accuracy in diagnosis of local recurrence and peritoneal dissemination, with complementary roles depending on histological type, anatomic location and tumoral volume. PMID- 22315682 TI - MAPK usage in periodontal disease progression. AB - In periodontal disease, host recognition of bacterial constituents, including lipopolysaccharide (LPS), induces p38 MAPK activation and subsequent inflammatory cytokine expression, favoring osteoclastogenesis and increased net bone resorption in the local periodontal environment. In this paper, we discuss evidence that the p38/MAPK-activated protein kinase-2 (MK2) signaling axis is needed for periodontal disease progression: an orally administered p38alpha inhibitor reduced the progression of experimental periodontal bone loss by reducing inflammation and cytokine expression. Subsequently, the significance of p38 signaling was confirmed with RNA interference to attenuate MK2-reduced cytokine expression and LPS-induced alveolar bone loss. MAPK phosphatase-1 (MKP 1), a negative regulator of MAPK activation, was also critical for periodontal disease progression. In MPK-1-deficient mice, p38-sustained activation increased osteoclast formation and bone loss, whereas MKP-1 overexpression dampened p38 signaling and subsequent cytokine expression. Finally, overexpression of the p38/MK2 target RNA-binding tristetraprolin (TTP) decreased mRNA stability of key inflammatory cytokines at the posttranscriptional level, thereby protecting against periodontal inflammation. Collectively, these studies highlight the importance of p38 MAPK signaling in immune cytokine production and periodontal disease progression. PMID- 22315684 TI - Behavioral factors of longevity. PMID- 22315685 TI - Is collective efficacy age graded? The development and evaluation of a new measure of collective efficacy for older adults. AB - Objectives. Community processes are key determinants of older adults' ability to age in place, but existing scales measuring these constructs may not provide accurate, unbiased measurements among older adults because they were designed with the concerns of child-rearing respondents in mind. This study examines the properties of a new theory-based measure of collective efficacy (CE) that accounts for the perspectives of older residents. Methods. Data come from the population-based Chicago Neighborhood Organization, Aging and Health study (N = 1,151), which surveyed adults aged 65 to 95. Using descriptive statistics, correlations, and factor analysis, we explored the acceptability, reliability, and validity of the new measure. Results. Principal component analysis indicated that the new scale measures a single latent factor. It had good internal consistency reliability, was highly correlated with the original scale, and was similarly associated with neighborhood exchange and disorder, self-rated health, mobility, and loneliness. The new scale also showed less age-differentiated nonresponse compared to the original scale. Discussion. The older adult CE scale has reliability and validity equivalent to that of the existing measure but benefits from a more developed theoretical grounding and reduced likelihood of age-related differential nonresponse. PMID- 22315686 TI - Does Meniere's Disease in the Elderly Present Some Peculiar Features? AB - Object. Aim of our study was to establish some peculiar features of Meniere's Disease (MD) in a group of elderly MD patients, in which the first vertigo spell happened when over 65 years old. Material and Methods. We analyzed a group of 73 younger than 65-years-old and a group of 30 elderly MD patients. All patients underwent a neurotological evaluation, an anamnestic evaluation including a lifetime history of migraine, and blood withdrawal for autoantibody screening. Results. Some differences were found between elderly and younger MD patients. Elderly MD patients presented a higher prevalence of Tumarkin attacks and a lower prevalence of lifetime history of migraine; moreover, they presented a faster develop of hearing loss and vertigo spells than a subgroup of 32 younger patients matched for the duration of illness. Conclusions. Some clinical features of MD in elderly have been pointed out. Particularly, the lower rate of migrainous history and positivity for autoantibodies often associated with MD, in our opinion, support the hypothesis of a vascular disorder acting as a predisposing factor for MD in elderly. PMID- 22315687 TI - A qualitative review of balance and strength performance in healthy older adults: impact for testing and training. AB - A continuously greying society is confronted with specific age-related health problems (e.g., increased fall incidence/injury rate) that threaten both the quality of life of fall-prone individuals as well as the long-term sustainability of the public health care system due to high treatment costs of fall-related injuries (e.g., femoral neck fracture). Thus, intense research efforts are needed from interdisciplinary fields (e.g., geriatrics, neurology, and exercise science) to (a) elucidate neuromuscular fall-risk factors, (b) develop and apply adequate fall-risk assessment tools that can be administered in clinical practice, and (c) develop and design effective intervention programs that have the potential to counteract a large number of fall-risk factors by ultimately reducing the number of falls in the healthy elderly. This paper makes an effort to present the above raised research topics in order to provide clinicians, therapists, and practitioners with the current state-of-the-art information. PMID- 22315688 TI - The importance of velocity acceleration to flow-mediated dilation. AB - The validity of the flow-mediated dilation test has been questioned due to the lack of normalization to the primary stimulus, shear stress. Shear stress can be calculated using Poiseuille's law. However, little attention has been given to the most appropriate blood velocity parameter(s) for calculating shear stress. The pulsatile nature of blood flow exposes the endothelial cells to two distinct shear stimuli during the cardiac cycle: a large rate of change in shear at the onset of flow (velocity acceleration), followed by a steady component. The parameter typically entered into the Poiseuille's law equation to determine shear stress is time-averaged blood velocity, with no regard for flow pulsatility. This paper will discuss (1) the limitations of using Posieuille's law to estimate shear stress and (2) the importance of the velocity profile-with emphasis on velocity acceleration-to endothelial function and vascular tone. PMID- 22315689 TI - Medical transport of children with complex chronic conditions. AB - One of the most notable trends in child health has been the increase in the number of children with special health care needs, including those with complex chronic conditions. Care of these children accounts for a growing fraction of health care resources. We examine recent developments in health care, especially with regard to medical transport and prehospital care, that have emerged to adapt to this remarkable demographic trend. One such development is the focus on care coordination, including the dissemination of the patient-centered medical home concept. In the prehospital setting, the need for greater coordination has catalyzed the development of the emergency information form. Training programs for prehospital providers now incorporate specific modules for children with complex conditions. Another notable trend is the shift to a family-centered model of care. We explore efforts toward regionalization of care, including the development of specialized pediatric transport teams, and conclude with recommendations for a research agenda. PMID- 22315690 TI - Gender Differences in Modifying Lumbopelvic Motion during Hip Medial Rotation in People with Low Back Pain. AB - Reducing increased or early lumbopelvic motion during trunk or limb movements may be an important component of low back pain treatment. The ability to reduce lumbopelvic motion may be influenced by gender. The purpose of the current study was to examine the effect of gender on the ability of people with low back pain to reduce lumbopelvic motion during hip medial rotation following physical therapy treatment. Lumbopelvic rotation and hip rotation before the start of lumbopelvic rotation were assessed pre- and posttreatment for 16 females and 15 males. Both men and women decreased lumbopelvic rotation and completed more hip rotation before the start of lumbopelvic rotation post-treatment compared to pre treatment. Men demonstrated greater lumbopelvic rotation and completed less hip rotation before the start of lumbopelvic rotation than women both pre- and post treatment. Both men and women reduced lumbopelvic motion relative to their starting values, but, overall, men still demonstrated greater and earlier lumbopelvic motion. These results may have important implications for understanding differences in the evaluation and treatment of men and women with low back pain. PMID- 22315691 TI - Changes in Cytokines of the Bone Microenvironment during Breast Cancer Metastasis. AB - It is commonly accepted that cancer cells interact with host cells to create a microenvironment favoring malignant colonization. The complex bone microenvironment produces an ever changing array of cytokines and growth factors. In this study, we examined levels of MCP-1, IL-6, KC, MIP-2, VEGF, MIG, and eotaxin in femurs of athymic nude mice inoculated via intracardiac injection with MDA-MB-231(GFP) human metastatic breast cancer cells, MDA-MB-231BRMS1(GFP), a metastasis suppressed variant, or PBS. Animals were euthanized (day 3, 11, 19, 27 after injection) to examine femoral cytokine levels at various stages of cancer cell colonization. The epiphysis contained significantly more cytokines than the diaphysis except for MIG which was similar throughout the bone. Variation among femurs was evident within all groups. By day 27, MCP-1, MIG, VEGF and eotaxin levels were significantly greater in femurs of cancer cell-inoculated mice. These pro-osteoclastic and angiogenic cytokines may manipulate the bone microenvironment to enhance cancer cell colonization. PMID- 22315692 TI - Experience of initial symptoms of breast cancer and triggers for action in ethiopia. AB - Objective. This study assessed the initial experiences, symptoms, and actions of patients in Ethiopia ultimately determined to have breast cancer. Methods. 69 participants in a comprehensive breast cancer treatment program at the main national cancer hospital in Ethiopia were interviewed using mixed qualitative and quantitative approaches. Participants' narratives of their initial cancer experience were coded and analyzed for themes around their symptoms, time to seeking advice, triggers for action, and contextual factors. The assessment was approved by the Addis Ababa University Faculty of Medicine Institutional Review Board. Results. Nearly all women first noticed lumps, though few sought medical advice within the first year (average time to action: 1.5 years). Eventually, changes in their symptoms motivated most participants to seek advice. Most participants did not think the initial lump would be cancer, nor was a lump of any particular concern until symptoms changed. Conclusion. Given the frequency with which lumps are the first symptom noticed, raising awareness among participants that lumps should trigger medical consultation could contribute significantly to more rapid medical advice-seeking among women in Ethiopia. Primary care sites should be trained and equipped to offer evaluation of lumps so that women can be referred appropriately for assessment if needed. PMID- 22315693 TI - Improved acuity and dexterity but unchanged touch and pain thresholds following repetitive sensory stimulation of the fingers. AB - Neuroplasticity underlies the brain's ability to alter perception and behavior through training, practice, or simply exposure to sensory stimulation. Improvement of tactile discrimination has been repeatedly demonstrated after repetitive sensory stimulation (rSS) of the fingers; however, it remains unknown if such protocols also affect hand dexterity or pain thresholds. We therefore stimulated the thumb and index finger of young adults to investigate, besides testing tactile discrimination, the impact of rSS on dexterity, pain, and touch thresholds. We observed an improvement in the pegboard task where subjects used the thumb and index finger only. Accordingly, stimulating 2 fingers simultaneously potentiates the efficacy of rSS. In fact, we observed a higher gain of discrimination performance as compared to a single-finger rSS. In contrast, pain and touch thresholds remained unaffected. Our data suggest that selecting particular fingers modulates the efficacy of rSS, thereby affecting processes controlling sensorimotor integration. PMID- 22315694 TI - Accumulation of vesicle-associated human tau in distal dendrites drives degeneration and tau secretion in an in situ cellular tauopathy model. AB - We used a nontransgenic cellular tauopathy model in which individual giant neurons in the lamprey CNS (ABCs) overexpress human tau isoforms cell autonomously to characterize the still poorly understood consequences of disease associated tau processing in situ. In this model, tau colocalizes with endogenous microtubules and is nontoxic when expressed at low levels, but is misprocessed by a toxicity-associated alternative pathway when expressed above levels that saturate dendritic microtubules, causing abnormally phosphorylated, vesicle associated tau to accumulate in ABC distal dendrites. This causes localized microtubule loss and eventually dendritic degeneration, which is preceded by tau secretion to the extracellular space. This sequence is reiterated at successively more proximal dendritic locations over time, suggesting that tau-induced dendritic degeneration is driven by distal dendritic accumulation of hyperphosphorylated, vesicle-associated tau perpetuated by localized microtubule loss. The implications for the diagnosis and treatment of human disease are discussed. PMID- 22315695 TI - Divergent evolution of male aggressive behaviour: another reproductive isolation barrier in extremophile poeciliid fishes? AB - Reproductive isolation among locally adapted populations may arise when immigrants from foreign habitats are selected against via natural or (inter )sexual selection (female mate choice). We asked whether also intrasexual selection through male-male competition could promote reproductive isolation among populations of poeciliid fishes that are locally adapted to extreme environmental conditions [i.e., darkness in caves and/or toxic hydrogen sulphide (H(2)S)]. We found strongly reduced aggressiveness in extremophile P. oecilia mexicana, and darkness was the best predictor for the evolutionary reduction of aggressiveness, especially when combined with presence of H(2)S. We demonstrate that reduced aggression directly translates into migrant males being inferior when paired with males from non-sulphidic surface habitats. By contrast, the phylogenetically old sulphur endemic P. sulphuraria from another sulphide spring area showed no overall reduced aggressiveness, possibly indicating evolved mechanisms to better cope with H(2)S. PMID- 22315696 TI - Rapid Evolution of Assortative Fertilization between Recently Allopatric Species of Drosophila. AB - The virilis group of Drosophila represents a relatively unexplored but potentially useful model to investigate the genetics of speciation. Good resolution of phylogenetic relationships and the ability to obtain fertile hybrid offspring make the group especially promising for analysis of genetic changes underlying reproductive isolation separate from hybrid sterility and inviability. Phylogenetic analyses reveal a close relationship between the sister species, Drosophila americana and D. novamexicana, yet excepting their contemporary allopatric distributions, factors that contribute to reproductive isolation between this species pair remain uncharacterized. A previous report has shown reduced progeny numbers in laboratory crosses between the two species, especially when female D. novamexicana are crossed with male D. americana. We show that the hatch rate of eggs produced from heterospecific matings is reduced relative to conspecific matings. Failure of eggs to hatch, and consequent reduction in hybrid progeny number, is caused by low fertilization success of heterospecific sperm, thus representing a postmating, prezygotic incompatibility. Following insemination, storage and motility of heterospecific sperm is visibly compromised in female D. novamexicana. Our results provide evidence for a mechanism of reproductive isolation that is seldom reported for Drosophila species, and indicate the rapid evolution of postmating, prezygotic reproductive barriers in allopatry. PMID- 22315697 TI - A Phenotypic Point of View of the Adaptive Radiation of Crested Newts (Triturus cristatus Superspecies, Caudata, Amphibia). AB - The divergence in phenotype and habitat preference within the crested newt Triturus cristatus superspecies, examined across different ontogenetic stages, provides an excellent setting to explore the pattern of adaptive radiation. The crested newts form a well-supported monophyletic clade for which at least the full mitochondrial DNA phylogeny is resolved. Here we summarise studies that explored the variation in morphological (larval and adult body form, limb skeleton, and skull shape) and other phenotypic traits (early life history, developmental sequences, larval growth rate, and sexual dimorphism) to infer the magnitude and direction of evolutionary changes in crested newts. The phenotypic traits show a high level of concordance in the pattern of variation; there is a cline-like variation, from T. dobrogicus, via T. cristatus, T. carnifex, and T. macedonicus to the T. karelinii group. This pattern matches the cline of ecological preferences; T. dobrogicus is relatively aquatic, followed by T. cristatus. T. macedonicus, T. carnifex, and the T. karelinii group are relatively terrestrial. The observed pattern indicates that phenotypic diversification in crested newts emerged due to an evolutionary switch in ecological preferences. Furthermore, the pattern indicates that heterochronic changes, or changes in the timing and rate of development, underlie the observed phenotypic evolutionary diversification. PMID- 22315698 TI - Inter- and intraspecific variation in Drosophila genes with sex-biased expression. AB - Genes with sexually dimorphic expression (sex-biased genes) often evolve rapidly and are thought to make an important contribution to reproductive isolation between species. We examined the molecular evolution of sex-biased genes in Drosophila melanogaster and D. ananassae, which represent two independent lineages within the melanogaster group. We find that strong purifying selection limits protein sequence variation within species, but that a considerable fraction of divergence between species can be attributed to positive selection. In D. melanogaster, the proportion of adaptive substitutions between species is greatest for male-biased genes and is especially high for those on the X chromosome. In contrast, male-biased genes do not show unusually high variation within or between populations. A similar pattern is seen at the level of gene expression, where sex-biased genes show high expression divergence between species, but low divergence between populations. In D. ananassae, there is no increased rate of adaptation of male-biased genes, suggesting that the type or strength of selection acting on sex-biased genes differs between lineages. PMID- 22315699 TI - The evolving role of selenium in the treatment of graves' disease and ophthalmopathy. AB - Graves' disease (GD) and ophthalmopathy (GO) are organ-specific autoimmune inflammatory disorders characterized by a complex pathogenesis. The inflammatory process is dominated by an imbalance of the antioxidant-oxidant mechanism, increased production of radical oxygen species (ROS), and cytokines which sustain the autoimmune process and perpetuate the disease. Recently, selenium, which is a powerful antioxidant, has been successfully applied in patients with mild GO, slowing the progression of disease, decreasing the clinical activity score, and appreciably improving the quality of life. The mechanisms of selenium action are variable. The aim of this review is to summarize the actions of selenium in GD and GO. Selenium as selenocysteine is incorporated in selenoproteins, such as glutathione peroxidase which catalyzes the degradation of hydrogen peroxide and lipid hydroperoxide that are increasingly produced in hyperthyroidism. Moreover, selenium decreases the formation of proinflammatory cytokines, while it contributes, in synergy with antithyroid drugs, to stabilization of the autoimmune process in GD and alleviation of GO. It is now to be clarified whether enforced nutritional supplementation has the same results and whether prolonging selenium administration may have an impact on the prevention of disease. PMID- 22315700 TI - Medicinal plants used by various tribes of bangladesh for treatment of malaria. AB - It has been estimated that 300-500 million malaria infections occur on an annual basis and causes fatality to millions of human beings. Most of the drugs used for treatment of malaria have developed drug-resistant parasites or have serious side effects. Plant kingdom has throughout the centuries proved to be efficient source of efficacious malarial drugs like quinine and artemisinin. Since these drugs have already developed or in the process of developing drug resistance, it is important to continuously search the plant kingdom for more effective antimalarial drugs. In this aspect, the medicinal practices of indigenous communities can play a major role in identification of antimalarial plants. Bangladesh has a number of indigenous communities or tribes, who because of their living within or in close proximity to mosquito-infested forest regions, have high incidences of malaria. Over the centuries, the tribal medicinal practitioners have treated malaria with various plant-based formulations. The objective of the present study was to conduct an ethnomedicinal survey among various tribes of Bangladesh to identify the plants that they use for treatment of the disease. Surveys were conducted among seven tribes, namely, Bawm, Chak, Chakma, Garo, Marma, Murong, and Tripura, who inhabit the southeastern or northcentral forested regions of Bangladesh. Interviews conducted with the various tribal medicinal practitioners indicated that a total of eleven plants distributed into 10 families were used for treatment of malaria and accompanying symptoms like fever, anemia, ache, vomiting, and chills. Leaves constituted 35.7% of total uses followed by roots at 21.4%. Other plant parts used for treatment included barks, seeds, fruits, and flowers. A review of the published scientific literature showed that a number of plants used by the tribal medicinal practitioners have been scientifically validated in their uses. Taken together, the plants merit further scientific research towards possible discovery of novel compounds that can be used to successfully treat malaria with less undesirable sideeffects. PMID- 22315701 TI - Antimalarial Effects of Iranian Flora Artemisia sieberi on Plasmodium berghei In Vivo in Mice and Phytochemistry Analysis of Its Herbal Extracts. AB - The aim of this study is pharmacochemistry of Iranian flora Artemisia sieberi and its antimalarial effects on Plasmodium berghei in vivo. This is the first application of A. sieberi for treatment of murine malaria. A. sieberi were collected at flowering stage from the Khorassan and Semnan provinces of Iran; the aerial parts were air-dried at room temperature and then powdered. The powder was macerated in methanol, filtered with Bokhner hopper and solvent was separated in rotary evaporator. Total herbal extract was subsequently processed for ether and chloroform extracts preparation. The toxicity of herbal extract was assessed on naive NMRI mice with high, average and low doses; then pathophysiological signs were assessed. Finally, the antimalarial efficacy was investigated on two groups of Plasmodium berghei infected mice. Percentage of parasitaemia and pathophysiology were also evaluated. The results of this assessment showed no toxicity even by high concentration of herbal extract. A significant reduction in percentage of parasitaemia was observed; no alterations of hepatosplenomegaly and body weight were indicated in study group. A. sieberi extracts showed antimalarial effects against murine malaria with some efficacies on reducing pathophysiology. However, there is requirement to find the major component of this herbal extract by further studies. PMID- 22315702 TI - Pathology and diagnosis of central nervous system infections. PMID- 22315703 TI - Therapeutic hypothermia in stroke. PMID- 22315704 TI - Stroke in the young. PMID- 22315705 TI - Asymptomatic and symptomatic carotid stenosis: an obsolete classification? AB - Since many years, clinical decisions about the management of patients with carotid stenosis have been based on the distinction between "asymptomatic" and "symptomatic" presentations. This was also reflected by the design of previous studies on the surgical versus conservative treatment and of current studies on interventional treatment versus surgery. Both terms, however, only address different phases of activity of the one and the same condition and blur the significant message that carotid stenosis is a most important marker of systemic atherosclerosis, which is accompanied by a much higher risk of cardiovascular events rather than stroke. As a consequence, early diagnosis and followup during best medical treatment, life-style management, regular cardiovascular assessment, and good control of all vascular risk factors should be recommended in all patients with carotid stenosis-whether identified in the long-lasting "silent" or short-lasting "vulnerable" period lasting only a few weeks after cerebral ischemia. Patients in this short time window benefit from additional carotid intervention, under the condition of an individually favorable benefit-risk ratio ("individual vulnerability"). PMID- 22315706 TI - Small vessel cerebrovascular disease: the past, present, and future. AB - Brain infarction due to small vessel cerebrovascular disease (SVCD)-also known as small vessel infarct (SVI) or "lacunar" stroke-accounts for 20% to 25% of all ischemic strokes. Historically, SVIs have been associated with a favorable short term prognosis. However, studies over the years have demonstrated that SVCD/SVI is perhaps a more complex and less benign phenomenon than generally presumed. The currently employed diagnostic and therapeutic strategies are based upon historical and contemporary perceptions of SVCD/SVI. What is discovered in the future will unmask the true countenance of SVCD/SVI and help furnish more accurate prognostication schemes and effective treatments for this condition. This paper is an overview of SVCD/SVI with respect to the discoveries of the past, what is known now, and what will the ongoing investigations evince in the future. PMID- 22315707 TI - Functional exercise and physical fitness post stroke: the importance of exercise maintenance for motor control and physical fitness after stroke. AB - It is argued that all stroke patients, indifferent of disability, have the same possibility to improve with training. The aim of the study was to follow and register functional improvements in two groups with different functional capacities at baseline for a period of 36 months. Stroke patients were recruited and divided into groups related to their functional status at baseline. During the acute rehabilitation, both groups received functional task-oriented training, followed by regular self- or therapeutic driven training the first year after stroke and varied exercise patterns the following 24 months. The participants were tested on admission, and at three, six, twelve, and thirty-six months after the onset of stroke. Both groups improved functional activity up to six months which then stabilized up to twelve months to decline somewhat at thirty-six months after stroke. Change scores indicate a greater potential for rehabilitation in the MAS <=35 in relation to group MAS >35 although the functional capacity was higher in the latter. This indicates the importance of maintaining exercise and training for all persons after stroke. PMID- 22315708 TI - Magnetic Resonance Enterography Findings in Crohn's disease in the Pediatric Population and Correlation with Fluoroscopic and Multidetector Computed Tomographic Techniques. AB - Traditionally, fluoroscopic examinations such as enteroclysis, upper GI studies, and small bowel follow through exams have been the procedures of choice in evaluating inflammatory bowel disease (IBD) in pediatric populations. With the advent of multidetector computed tomography (MDCT), it has subsequently become a complementary examination in imaging inflammatory bowel disease. A major advantage of MDCT over fluoroscopic examination is its ability to directly visualize bowel mucosa, as well as demonstrate extra-enteric complications of IBD such as abscesses, fistulae, and sinus tracts. The major disadvantage of CT however is exposure to ionizing radiation, especially in IBD patients of the pediatric age group who maybe repeatedly imaged due to exacerbations. As a result, magnetic resonance enterography (MRE) is becoming increasingly important in the evaluation and follow-up of pediatric patients with IBD. This pictorial essay will summarize the multi-modality imaging findings of IBD with emphasis on MRE including the imaging protocol and procedure. For the purposes of this article, patients less than 17 years of age have been considered to represent the pediatric population. PMID- 22315709 TI - Angiographic-CT-FDG-Pathologic Correlations of the Incidentally Discovered Adrenal Mass. AB - During abdominal ultrasonography of a 37-year-old man a 3.2 cm hypoechoic mass in the right hepatic lobe was found incidentally. This prompted an abdominal CT, an FDG PET/CT, and an angiography to evaluate the nature of the mass. Laboratory data showed positive anti-HBs/anti-HBe, and negative HCV antibody. The alfa fetoprotein and liver function tests were within normal limits. Contrast-enhanced CT found an enhanced hepatic tumor and primary hepatocellular carcinoma was suspected. PET/CT revealed no abnormal FDG accumulation in the right hepatic mass. The digital subtraction angiographies of the right inferior phrenic artery and right renal artery revealed a hypervascular tumor in the right adrenal gland. Therefore, a diagnosis of a right adrenal tumor was made. Serum aldosterone, serum cortisol, and urine vanillylmandelic acid, and catecholamine were all within normal limits. Laparoscopic right adrenalectomy was performed and adrenal cortical adenoma was diagnosed on a histological study. PMID- 22315710 TI - Temporal and pontine involvement in a case of herpes simplex encephalitis, presenting as kluver bucy syndrome - a case report. AB - Bilateral temporal and frontal lobe involvement is a common characteristic of herpes simplex encephalitis (HSE). Clinical sequelae of herpes simplex encephalitis may manifest sometimes as Kluver Bucy syndrome (KBS). In herpes simplex encephalitis, apart from frontal lobe, extra temporal involvement is rare and uncommon. We report a case of HSE manifesting clinically as KBS with a rare radiological finding of temporal and extratemporal involvement of pons. PMID- 22315711 TI - Struma ovarii with papillary thyroid carcinoma. AB - Struma ovarii is an uncommon condition, in which thyroid tissue is the predominant or exclusive element in an ovarian teratoma. Thyroid tissue may demonstrate the same spectrum of pathological features as in the normal thyroid including benign and malignant changes. We present a case of papillary thyroid carcinoma arising in a struma ovarii of the left ovary in a 21-year-old female. PMID- 22315712 TI - Computed tomography findings in xanthogranulomatous pyelonephritis. AB - BACKGROUND: Xanthogranulomatous pyelonephritis (XGN) is an uncommon condition characterized by chronic suppurative renal inflammation that leads to progressive parenchymal destruction. PURPOSE: To review the computed tomography (CT) findings of patients diagnosed with XGN. MATERIALS AND METHODS: A retrospective review of CT findings in patients with histologically proven XGN was carried out. RESULTS: Thirteen CT examinations of 11 patients were analyzed. Renal enlargement was demonstrable on the affected side in all patients. Nine patients (82%) had multiple dilated calyces and abnormal parenchyma. Six patients (55%) had a renal pelvis or upper ureteric calculus causing obstruction. Three patients (27%) had focal fat deposits identifiable within the inflamed renal parenchyma. Two patients had renal abscesses. Ten patients (91%) had extrarenal extension of the inflammatory changes. Three patients (27%) demonstrated extensive retroperitoneal inflammation. CONCLUSION: Unilateral renal enlargement and inflammation were the most consistent findings of XGN on CT. Perinephric inflammation and collections or abscess should also alert the radiologist to the possibility of this diagnosis. PMID- 22315713 TI - Presenilins and gamma-secretase: structure, function, and role in Alzheimer Disease. AB - Presenilins were first discovered as sites of missense mutations responsible for early-onset Alzheimer disease (AD). The encoded multipass membrane proteins were subsequently found to be the catalytic components of gamma-secretases, membrane embedded aspartyl protease complexes responsible for generating the carboxyl terminus of the amyloid beta-protein (Abeta) from the amyloid protein precursor (APP). The protease complex also cleaves a variety of other type I integral membrane proteins, most notably the Notch receptor, signaling from which is involved in many cell differentiation events. Although gamma-secretase is a top target for developing disease-modifying AD therapeutics, interference with Notch signaling should be avoided. Compounds that alter Abeta production by gamma secretase without affecting Notch proteolysis and signaling have been identified and are currently at various stages in the drug development pipeline. PMID- 22315714 TI - Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature. AB - Biochemical and neuropathological studies of brains from individuals with Alzheimer disease (AD) provide clear evidence for an activation of inflammatory pathways, and long-term use of anti-inflammatory drugs is linked with reduced risk to develop the disease. As cause and effect relationships between inflammation and AD are being worked out, there is a realization that some components of this complex molecular and cellular machinery are most likely promoting pathological processes leading to AD, whereas other components serve to do the opposite. The challenge will be to find ways of fine tuning inflammation to delay, prevent, or treat AD. PMID- 22315715 TI - Endothelial cell heterogeneity. AB - The endothelial lining of blood vessels shows remarkable heterogeneity in structure and function, in time and space, and in health and disease. An understanding of the molecular basis for phenotypic heterogeneity may provide important insights into vascular bed-specific therapies. First, we review the scope of endothelial heterogeneity and discuss its proximate and evolutionary mechanisms. Second, we apply these principles, together with their therapeutic implications, to a representative vascular bed in disease, namely, tumor endothelium. PMID- 22315716 TI - Semaphorins in angiogenesis and tumor progression. AB - The semaphorins were initially described as axon guidance factors, but have recently been implicated in a variety of physiological and developmental functions, including regulation of immune response, angiogenesis, and migration of neural crest cells. The semaphorin family contains more than 30 genes divided into seven subfamilies, all of which are characterized by the presence of a sema domain. The semaphorins transduce their signals by binding to one of the nine receptors belonging to the plexin family, or, in the case of the class 3 semaphorins, by binding to one of the two neuropilin receptors. Additional receptors, which form complexes with these primary semaphorin receptors, are also frequently involved in semaphorin signaling. Recent evidence suggests that some semaphorins can act as antiangiogenic and/or antitumorigenic agents whereas other semaphorins promote tumor progression and/or angiogenesis. Furthermore, loss of endogenous inhibitory semaphorin expression or function on one hand, and overexpression of protumorigenic semaphorins on the other hand, is associated with the progression of some tumor types. PMID- 22315717 TI - The Antibody Response against HIV-1. AB - Neutralizing antibodies (NAbs) typically play a key role in controlling viral infections and contribute to the protective effect of many successful vaccines. In the case of HIV-1 infection, there is compelling data in experimental animal models that NAbs can prevent HIV-1 acquisition, although there is no similar data in humans and their role in controlling established infection in humans is also limited. It is clear HIV-specific NAbs drive the evolution of the HIV-1 envelope glycoprotein within an infected individual. The virus's ability to evade immune selection may be the main reason HIV-1 NAbs exert limited control during infection. The extraordinary antigenic diversity of HIV-1 also presents formidable challenges to defining NAbs that could provide broad protection against diverse circulating HIV-1 strains. Several new potent monoclonal antibodies (MAbs) have been identified, and are beginning to yield important clues into the epitopes common to diverse HIV-1 strains. In addition, antibodies can also act in concert with effector cells to kill HIV-infected cells; this could provide another mechanism for antibody-mediated control of HIV-1 replication. Understanding the impact of antibodies on HIV-1 transmission and pathogenesis is critical to helping move forward with rational HIV-1 vaccine design. PMID- 22315718 TI - Nonpathogenic simian immunodeficiency virus infections. AB - The simian immunodeficiency viruses (SIVs) are a diverse group of viruses that naturally infect a wide range of African primates, including African green monkeys (AGMs) and sooty mangabey monkeys (SMs). Although natural infection is widespread in feral populations of AGMs and SMs, this infection generally does not result in immunodeficiency. However, experimental inoculation of Asian macaques results in an immunodeficiency syndrome remarkably similar to human AIDS. Thus, natural nonprogressive SIV infections appear to represent an evolutionary adaptation between these animals and their primate lentiviruses. Curiously, these animals maintain robust virus replication but have evolved strategies to avoid disease progression. Adaptations observed in these primates include phenotypic changes to CD4(+) T cells, limited chronic immune activation, and altered mucosal immunity. It is probable that these animals have achieved a unique balance between T-cell renewal and proliferation and loss through activation-induced apoptosis, and virus-induced cell death. A clearer understanding of the mechanisms underlying the lack of disease progression in natural hosts for SIV infection should therefore yield insights into the pathogenesis of AIDS and may inform vaccine design. PMID- 22315719 TI - Virus infections in type 1 diabetes. AB - The precise etiology of type 1 diabetes (T1D) is still unknown, but viruses have long been suggested as a potential environmental trigger for the disease. However, despite decades of research, the body of evidence supporting a relationship between viral infections and initiation or acceleration of islet autoimmunity remains largely circumstantial. The most robust association with viruses and T1D involves enterovirus species, of which some strains have the ability to induce or accelerate disease in animal models. Several hypotheses have been formulated to mechanistically explain how viruses may affect islet autoimmunity and beta-cell decay. The recent observation that certain viral infections, when encountered at the right time and infectious dose, can prevent autoimmune diabetes illustrates that potential relationships may be more complex than previously thought. Here, we provide a concise summary of data obtained in mouse models and humans, and identify future avenues toward a better characterization of the association between viruses and T1D. PMID- 22315720 TI - Genetics of type 1 diabetes. AB - Genetic susceptibility to type 1 diabetes (T1D) has been a subject of intensive study for nearly four decades. This article will present the history of these studies, beginning with observations of the Human Leukocyte Antigen (HLA) association in the 1970s, through the advent of DNA-based genotyping methodologies, through recent large, international collaborations and genome-wide association studies. More than 40 genetic loci have been associated with T1D in multiple studies; however, the HLA region, with its multiple genes and extreme polymorphism at those loci, remains by far the greatest contributor to the genetic susceptibility to T1D. Even after decades of study, the complete story has yet to unfold, and exact mechanisms by which HLA and other associated loci confer T1D susceptibility remain elusive. PMID- 22315721 TI - Genetics of Parkinson's disease. AB - Fifteen years of genetic research in Parkinson's disease (PD) have led to the identification of several monogenic forms of the disorder and of numerous genetic risk factors increasing the risk to develop PD. Monogenic forms, caused by a single mutation in a dominantly or recessively inherited gene, are well established, albeit relatively rare types of PD. They collectively account for about 30% of the familial and 3%-5% of the sporadic cases. In this article, we will summarize the current knowledge and understanding of the molecular genetics of PD. In brief, we will review familial forms of PD, basic genetic principles of inheritance (and their exceptions in PD), followed by current methods for the identification of PD genes and risk factors, and implications for genetic testing. PMID- 22315723 TI - Deciphering Alzheimer disease. AB - Alzheimer disease represents an insidious impairment of intellect and emotional well-being. However, recent advances in biochemical pathology and human genetics offer promise that effective therapeutic agents may soon be developed. PMID- 22315724 TI - [Combined resection of the thoracic wall and diaphragm for pulmonary metastasis of malignant fibrous histiocytoma]. PMID- 22315725 TI - [Imaging diagnosis: Q & A. Mediastinal teratoma]. PMID- 22315722 TI - Inflammation and adaptive immunity in Parkinson's disease. AB - The immune system is designed to protect the host from infection and injury. However, when an adaptive immune response continues unchecked in the brain, the proinflammatory innate microglial response leads to the accumulation of neurotoxins and eventual neurodegeneration. What drives such responses are misfolded and nitrated proteins. Indeed, the antigen in Parkinson's disease (PD) is an aberrant self-protein, although the adaptive immune responses are remarkably similar in a range of diseases. Ingress of lymphocytes and chronic activation of glial cells directly affect neurodegeneration. With this understanding, new therapies aimed at modulating the immune system's response during PD could lead to decreased neuronal loss and improved clinical outcomes for disease. PMID- 22315726 TI - Peoples and states after 1989: the political costs of incomplete national revolutions. PMID- 22315727 TI - Born and made: sisters, brothers, and the "Deceased Wife's Sister Bill". PMID- 22315728 TI - Crimes and pardons: bourgeois justice, gendered virtue, and the criminalized other in eighteenth-century France. PMID- 22315729 TI - Dying to tell: sexuality and suicide in Imperial Japan. PMID- 22315732 TI - The representation of female desire in early modern pornographic texts, 1660 1745. PMID- 22315733 TI - [The pogrom in Kielce and its influence on the remaining Jews in Poland]. PMID- 22315734 TI - [Demographic trends in Soviet Jewry in the 1970's: first findings of the 1979 census]. PMID- 22315735 TI - Slavery in the Sudan in history. PMID- 22315736 TI - The 11 o'clock flog: women, work and labour law in the British Caribbean. PMID- 22315737 TI - [Breast and endocrine tumor-recent progress and future view for treatment of breast cancer-]. PMID- 22315738 TI - Author's reply: To PMID 19075406. PMID- 22315739 TI - Educating undergraduates on one health. PMID- 22315740 TI - [Monologue by a referee: how to write a theses (2)]. PMID- 22315741 TI - The Angolan-Afro-Brazilian cultural connections. PMID- 22315742 TI - Is the ghost of tropical sprue re-surfacing after its obituary? PMID- 22315743 TI - Survival of elderly/dialysis patients--a single center study from India. AB - OBJECTIVE: In the absence of national registry and uniformity of treatment, survival of patients on dialysis in our country has been variedly reported. There are no published data on survival of elderly patients (>65 years) on dialysis. Because of several social, economical and practical reasons (mentioned below), not many elderly chronic kidney disease patients opt for dialysis. It is worth while to look into the data of survival of elderly CKD (chronic kidney disease) patients on dialysis to justify the treatment. All CKD patients who continued dialysis for more than 1 month at our center from 1st November 2006 to 31st August 2009 were included in the analysis. Patients who moved to their native place after initiation of dialysis, underwent transplant, discontinued dialysis for personal reasons, or died in the first month were excluded. The survival analysis (Kaplan-Meier) and the demographics were calculated for the elderly group and compared with the young ones (Independent sample T-test). 86 adult patients were included in the retrospective survival analysis, out of which 18 were elderly (21%). Mean age of elderly patients on dialysis was 72.3 +/- 7 years. 77.7 % were males and 77.7 % were diabetics. Median survival of these patients was 25.6 months (SE 10, and 95% CI 5.9 - 45.3) while the younger ones had a median survival of 79.6 months (SE 7.9, 95% CI 64 - 95.3). 24 months survival calculated from KM data set was 41.1% in the elderly whereas it was 96.9% in the young age group. It is conclude that Median survival of elderly dialysis patients is more than 2 years and 2 year survival is more than 40%. Elderly CKD patients, hence, should be encouraged for renal replacement therapy rather than discouraging them with poor survival. PMID- 22315744 TI - Hair dye poisoning in Bundelkhand region (prospective analysis of hair dye poisoning cases presented in Department of Medicine, MLB Medical College, Jhansi). AB - AIMS OF STUDY: Hair dye (Paraphenylene di-amine, PPD) poisoning has high morbidity and mortality and its incidence has increased dramatically in the past 4 years. A prospective study was planned to assess the clinical profile and outcome with different treatment approaches. MATERIAL AND METHODS: The material comprised of 1020 cases admitted in Medicine Department of MLB Medical College, Jhansi, U.P. from July 2004 to March 2009. Out of 1020 cases 697 cases were of stone hair dye poisoning and 323 cases were of other branded hair dyes (powdered form containing less amount of Paraphenylene diamine). Diagnosis was made solely on the basis of the history given by cases/attendant and symptoms of neck swelling, black coloured urine and muscular pain. The cases were thoroughly studied for different complications (renal, hepatic and cardiac etc) and were treated accordingly. RESULTS: Out of 1020 cases studied, majority were females in the age group of 15-45 yrs (n=734) while the rest were males. A total of 244 (23.92%) cases expired during treatment. Neck swelling, respiratory distress and whole body muscular pain were most common symptoms at presentation, oliguria, chest pain, palpitation, presyncope/syncope, pain in abdomen, nausea with vomiting and dysphagia were other common symptoms. CONCLUSION: Paraphenylene diamine is highly toxic. Cases who consumed up to 10 gm of PPD usually survived if they presented to hospital within 4 hour of dye ingestion. Severe edema of face, neck and floor of mouth, renal failure and myocarditis were poor prognostic factors. No deaths occurred in cases of Branded Hair dye ingestion. PMID- 22315745 TI - Spectrum of malabsorption in India--tropical sprue is still the leader. AB - INTRODUCTION: Two decades ago tropical sprue, Immunoproliferative Small Intestinal Disease (IPSID) and infections were common causes of malabsorption in India. It is possible that implementation of preventive health measures and improved sanitation may have changed the spectrum of disorders causing malabsorption. The aim of this study therefore was to assess the spectrum of malabsorption seen at our center during the past nine years. METHODOLOGY: Patients seen at our center with malabsorption from January 2000 to December 2008 were included in this study. The etiological, clinical and investigation details were recorded on uniform structured data forms. The data obtained was retrospectively analyzed. RESULTS: Malabsorption was detected in 124 patients during the study period. The mean age of patients was 31.9+16 years and 60.5% were males. Tropical sprue was the commonest etiology (29%) followed by celiac and Crohn's disease (15.3% each). Other important etiologies included parasitic infestations (9.7%) and immune deficiency disorders (5.6%). Intestinal tuberculosis was seen in only 2.4% patients. CONCLUSIONS: We are witnessing a change in etiological spectrum of malabsorption . Celiac disease and inflammatory bowel disorders are emerging as important causes and ImmunoProliferative Small Intestinal Disease (IPSID) and intestinal tuberculosis are on the decline. Tropical Sprue however continues to be the commonest cause as in the past. PMID- 22315746 TI - An open label, active controlled, multicentric clinical trial to assess the efficacy and safety of fluticasone furoate nasal spray in adult Indian patients suffering from allergic rhinitis. AB - BACKGROUND: Allergic rhinitis is a common upper respiratory tract inflammation associated with a significant morbidity in all the age groups. Fluticasone furoate is a new potent topical glucocorticoid for the treatment of allergic rhinitis. OBJECTIVE: To compare efficacy and safety of fluticasone furoate (FF) nasal spray 110 microg/day with fluticasone propionate (FP) nasal spray 200 microg/day for the relief of symptoms of allergic rhinitis in adult Indian patients. METHODS: Clinically symptomatic patients (n=220) with allergic rhinitis received treatment with FF or FP for 2 weeks in this comparative, open label, multicentric, clinical trial. Nasal symptoms (nasal congestion, rhinorrhea, nasal itching, and sneezing) and ocular symptoms (itching/burning eyes, tearing/watering eyes, and eye redness) were recorded on a 4-point categoric scale by the patients. The efficacy was assessed by the change in nasal and ocular symptom scores as their subtotals (Total Nasal Symptom Score and Total Ocular Symptom Score) and grand total (Total Symptom Score). RESULTS: FF produced significantly better improvement in Total Symptom Score (-10.4 +/- 3.2 vs. -8.9 +/- 3.5, p<0.005) and Total Nasal Symptom Score (-7.3 +/- 2.2 vs. -6.2 +/- 2.6, p<0.005) as compared to FP. Also a significantly larger percentage of patients achieved complete symptomatic relief with FF (45.3% vs. 31.4%, p<0.05). FF was also better tolerated than FP. CONCLUSION: FF nasal spray is significantly more effective and better tolerated than FP nasal spray for the treatment of allergic rhinitis in adult Indian patients. PMID- 22315747 TI - Stem cells and lung diseases. AB - This paper is designed to review our current understanding of the role of stem and progenitor cells in lung repair after injury and to review the current status of cell therapy approaches for lung diseases. It was found that circulating EPCs (endothelial progenitor cells) play roles in both acute lung injury and in fibrotic lung diseases. Circulating fibrocytes can contribute to the pathophysiology of fibrotic lung diseases and thus may be a potential therapeutic target. MSCs (mesenchymal cells) suppress lung injury and inflammation in several mouse models of inflammatory and immune-mediated lung diseases. In addition, novel areas of investigation have developed that include increasing exploration of three-dimensional culture systems and bioengineering approaches to generate functional lung tissue ex vivo and in vivo. PMID- 22315748 TI - Complicated silicosis in teflon-coated utensil making industry. PMID- 22315749 TI - Masquerading pneumonia--pulmonary contusion. AB - Pneumonia is diagnosed and treated with symptoms of fever, cough, expectoration and chest X ray showing evidence of consolidation. When a pattern of opacification does not fit into segmental or lobar pattern, reevaluation is essential. We report a case of 18 yr old boy with symptoms of respiratory infection, and X ray diagnosis suggestive of infective consolidation which turned out to be a case of pulmonary contusion. PMID- 22315750 TI - Ultra-short course of low-dose amiodarone-induced post-operative fatal pulmonary toxicity. AB - A 58-year-old male diabetic patient with severe left ventricular dysfunction and pulmonary arterial hypertension successfully underwent coronary artery by pass grafting (CABG) and was extubated 48 hours after surgery. Patient had atrial fibrillation on 3rd post-operative day requiring loading dose of amiodarone followed by maintenance dose to control the arrhythmia. On 4th post operative day patient became tachypnoiec and required higher concentration of oxygen to maintain SpO2 >90%. There was new infiltrates on the x-ray, which was more on right side. Initially treated as pulmonary infection and antifailure measures. The patient did not respond and the lesions progressed to opaque hemithorax by the 10th postoperative day. On 11th POD he was reintubated due to respiratory distress. After excluding pulmonary infections, pulmonary oedema, embolism and vascular obstruction, the possibility of drug induced pulmonary toxicity was considered. Hence amiodarone was withdrawn and steroid was initiated. There was good radiological and gas exchange improvement and he was extubated the following day. After one week course of steroids the infiltrates cleared and oxygenation also improved. Post CABG patients are prone for acute amiodarone toxicity and high index of suspicion is needed to diagnose this early so that fatal complication can be averted by timely intervention. PMID- 22315752 TI - Symmetrical peripheral gangrene and neurological manifestations in Plasmodium falciparum malaria. AB - A case of Falciparum malaria complicated with symmetrical peripheral gangrene has been discussed. This association is not very common as reported in the literature. The special feature of this case is that the patient had bilateral hypoglossal nerve palsy and the signs of pyramidal tract involvement which improved after conservative management. PMID- 22315751 TI - VACTERL Association. AB - Here we report a case of VACTERL ASSOCIATION in a twenty three years old married female patient primigravida with 3 months of amenorrhea admitted with history of fever and gastroenteritis along with congenital developmental defects such as scoliosis (V), small ventricular septal defect (C), right sided hemifacial dysmorphic features (right mandibular hypoplasia), small sized right sided kidney (R), bilateral hypoplastic thumb (L). For the diagnosis of VACTERL atleast three out of seven anomalies should be present while our patient had four anomalies. PMID- 22315753 TI - Double chambered right ventricle with ventricular septal defect presenting in adulthood. AB - Double-chambered right ventricle (DCRV) is a form of right ventricular outflow tract obstruction. It typically presents in childhood or adolescence. Only a handful of previous cases have been described in which DCRV occurred in adulthood. We report here a case of DCRV with ventricular septal defect (VSD) presenting in adulthood. PMID- 22315754 TI - Unusual presentation of brain abscess with uncommon organism in an immunocompetent person. AB - Multiple brain abscesses due to Listeria monocytogenes was detected in a 55 year old immunocompetent person who had history of progressive weakness for last three months with difficulty in micturition and abnormal behavior for the same duration. The patient was diagnosed six months back as tubercular meningitis and was put on ATD (now in continuation phase). After being diagnosed with Listeria, the patient was put on antibiotic therapy and responded dramatically. The abscess, by virtue of being relatively large and superficially located, was drained surgically. PMID- 22315755 TI - CA lung presenting with vasculitis. AB - A 67 year old man presented to us with petechial skin rash and blebs on the legs. He was on anti-tuberculous treatment for right sided pleural effusion since 1 month. A provisional diagnosis of Rifampicin induced drug rash was made and his effusion reaspirated and sent for AFB and cytology. The pleural fluid cytology demonstrated metastasis of adenocarcinoma and biopsy of skin lesion confirmed vasculitis. There was no thrombocytopenia. CT thorax showed right lower lobe mass with right sided pleural effusion. Thus a final diagnosis of skin manifestation of carcinoma of lung was made. This was a Paraneoplastic syndrome. PMID- 22315756 TI - Multiple myeloma presenting with hepatosplenomegaly. AB - Multiple myeloma, a clonal plasma cell disorder, commonly affects adults above 50 years age and accounts for about 10% of all hematological malignancies. Anemia, bone pains, renal failure are the most common symptoms at presentation. Though extra-medullary extra-osseous disease is well known in the course of the disease, initial presentation with extramedullary disease alone is rare. Such presentation may represent poor biology of the disease and/or advanced stage. Early diagnosis and treatment may improve outcomes. We herewith report the case of a 43 year old lady who presented with hepatosplenomegaly, without any classical manifestations of multiple myeloma and discuss the relevant literature. PMID- 22315757 TI - Pulmonary embolism after long duration rail travel: economy class syndrome or rail coach syndrome. AB - Pulmonary embolism after long duration air travel is well described. However it can also occur following a long duration rail or road transport. We present a case of 43 year old male who developed deep venous thrombosis and acute pulmonary embolism after a long rail journey. We propose to call it as rail coach syndrome and stress the need for taking the same preventive measures as recommended for airline passengers. PMID- 22315758 TI - Medical philately. Endocrine international congresses. PMID- 22315759 TI - Validation of the MDRF-IDRS through Boloor Diabetes Study. PMID- 22315760 TI - The stem cell controversy. PMID- 22315761 TI - Orthopaedic surgery--a new horizon. PMID- 22315762 TI - Studies on Ender's intramedullary nailing for closed tibial shaft fractures. AB - Low cost multiple flexible Ender's nails can be used in tibial shaft fractures in a non-ideal operating room set-up in India, also because of easy methodology. It is commonly used in femur and humerus but not in tibia. So we made the study in which prospective and consecutive patients were taken based on selection criteria. Forty patients were treated by the technique from August 2004 to May 2006. Twenty-seven patients (67.5%) were male, 28 patients (70%) had fracture type 4-2A of AO classification, 37 patients (92.5%) had acute injuries, delay in surgery by 1-2 weeks in 21 patients (52.5%), 30 patients (75%) had closed nailing, 35 patients (87.5%) needed 2 nails, 36 patients (90%) were operated by antegrade nailing approach and 23 patients (57.5%) had fracture union within 16 weeks. All the patients were evaluated based on pain,range of movement of knee and ankle,shortening and radiological union along with ability to perform daily activities like squatting,sitting cross-legged and the ability to walk. There was excellent result in 34 patients (85%), good in 5 patients (12.5%), fair/poor result in 1 patient (2.5%). The complications observed were soft tissue irritation of the proximal part of tibia due to protruding nail in 5 patients,infection at the entry portal in one patient and non-union in one patient. Ender's nailing can be a safe and alternative method of fixation of fracture shaft of tibia in rural India for poor patients in 'not well set-up'. PMID- 22315763 TI - Evaluation of pedicular screw fixation in dorsolumbar spinal injury. AB - Twenty-five patients with dorsolumbar spinal injury was treated by pedicular screw fixation along with direct or indirect decompression within 1 1/2 years period. Eighteen patients with incomplete neurodeficit had some amount of neurological recovery in terms of ASIA impairment scale but no neurological recovery was seen in 6 patients with complete neurological injury. Mean correction of kyphotic angle was 11.76 degrees. Mean postoperative increase in anterior vertebral body height was 43%. Complications like bed sore, superficial wound infections and peroperative dural tear were seen but all of which were treated successfully. Neurological deterioration after operation, screw pull out and implant failure were seen in none. This study indicates that short segment pedicular screw fixation is a safe and effective method for treatment of unstable spinal injury. PMID- 22315764 TI - Salivary gland tumours: profile and management at a tertiary cancer centre. AB - Salivary gland tumours comprise a varied group of benign and malignant neoplastic lesions posing a challenge to surgeon. To review the profile of salivary gland tumours presenting to a referral cancer centre and their overall management, a retrospective analysis of prospective head and neck cancer database of the surgical oncology department of Institute Rotary Cancer Hospital (IRCH), All India Institute of Medical Sciences (AIIMS) was performed. Forty patients of salivary gland tumours treated between 1995 and 2003 were analysed. All computations including recurrences and survival were carried out using the statistical package for social sciences (SPSS) for windows software (SPSS Inc, USA). The profile of salivary gland tumours presenting to a cancer centre setting was found to be different - 77.5% being malignant tumours and the remaining 22.5% werebenign tumours. Most common site of involvement was the parotid gland (72.5%). Muco-epidermoid carcinoma and adenocarcinomas were the most common histological types. Conservative resection was adequate for benign tumours. For primary malignant tumours, radical surgery with or without neck dissection and appropriate reconstruction, combined with postoperative radiotherapy was effective in achieving good locoregional control. Optimal management of primary tumour along with appropriate neck dissection including resection of the involved salivary gland is necessary for the management of metastatic salivary gland tumours. PMID- 22315765 TI - A comparative study of paediatric oral premedication: midazolam, ketamine and low dose combination of midazolam and ketamine. AB - In a prospective randomised double-blind trial, 90 patients aged 1-7 years (ASA I) undergoing elective surgery less than 90 minutes duration were allocated into three separate groups to compare the safety and effectiveness of oral midazolam, ketamine, and low dose combination of midazolam and ketamine for premedication in paediatric patients. Group M received midazolam 0.5 mg kg(-1), group K received ketamine 6mg kg(-1) and group C received combination of ketamine 2.5 mg kg(-1) and midazolam 0.25 mg kg(-1) orally in 0.2ml kg(-1) of sugar syrup to make it palatable. The sedation score and emotional state on a four -point scale, ease of parental separation, cooperation for venepuncture, ease of mask acceptance and peri-operative cardiorespiratory status were evaluated. Peri-operative incidence of vomiting, nystagmus, emergence phenomenon and postanesthetic recovery time were noted. In the present study it was found that C group was more effective in sedating the children within 10 minutes and 20 minutes, whereas, the combination and midazolam groups are comparable in sedating the children at 30 minutes. Side effects and recovery time were more in ketamine group. The recovery time was significantly less in group C. In conclusion oral combination of low dose ketamine and midazolam produced quick onset of satisfactory conscious sedation and more rapid recovery without significant side-effects, so that more children could be separated easily from their parents and provides smooth induction than the individual drug. PMID- 22315766 TI - Instant axis of rotation of L4-5 motion segment--a biomechanical study on cadaver lumbar spine. AB - The instant axis of rotation (IAR) is an important kinematic property to characterise of lumbar spine motion. The goal of this biomechanical study on cadaver lumbar spine was to determine the excursion of the IAR for flexion (FE), lateral bending (LB) and axial rotation (AR) motion at L4-5 segment. Ten cadaver lumbar spine specimens were tested in a 6 degrees-of-freedom spine tester with continuous clyclical loading using pure moment and follower pre-load, to produce physiological motion. The specimens were x-rayed and CT scanned prior to testing to identify marker position. Continuous motion tracking was done by Optotrak motion capture device. A continuous tracking of the IAR excursion was calculated from the continuous motions capturedata using a computer programme. IAR translates forward in flexion and backwards in extension with mean excursion of 26.5 mm (+/- 5.6 SD). During LB motion, IAR translates laterally in the same direction, and the mean excursion was 15.35 mm (+/- 8.75 SD). During axial rotation the IAR translates in the horizontal plane in a semicircular arc, around the centre of the vertebral body, but the IAR translates in the opposite direction of rotation. The IAR excursion was faster and larger during neutral zone motion in FE and LB, but uniform for AR motion. This is the first published data on the continuous excursion of IAR of a lumbar motion segment. The methodology is accurate and precise, but not practicable for in vivo testing. PMID- 22315767 TI - Albuminuria and neuropathy in newly detected diabetics: profile and correlation. AB - Neuropathy and nephropathy are two most common chronic complications of diabetes mellitus. Albuminuria and neuropathy has been found to be associated in patients with long standing diabetes. In the present study, the profiles of proteinuria and neuropathy have been studied in newly diagnosed cases of type 2 diabetes mellitus and attempt has been made to determine any relationship between the two. We studied 100 newly diagnosed ceases of type 2 diabetes mellitus and presence and type of neuropathy was assessed clinically and electrophysiologically. Albuminuria was detected by morning spot sample for albumin to creatinine ratio estimation. Results were analysed using appropriate statistical methods. It was found that 21 patients (21%) had proteinuria and 31 (31%) had neuropathy. Both were present in 16% patients and absent in 64% cases. The overall prevalence of neuropathy and proteinuria among study subjects was 36%. Isolated peripheral neuropathy was found in 9% patients, isolated autonomic neuropathy was found in 7% patients, and both were present in 15% cases. Proteinuria was mostly micro albuminuria (90.5%). Occurrence of albuminuria and neuropathy has been found to be significantly associated with increasing age. Concurrence of diabetic neuropathy and albuminuria has been found to be significantly associated. The present study reveals that presence of neuropathy as well as nephropathy is common in newly diagnosed cases of type 2 diabetes mellitus. Both these complications have been significantly associated with increasing age indicating the possibility of a longer duration of undetected diabetes among them. Concurrence of neuropathy and nephropathy found in this study suggests that microvascular complications go hand in hand. PMID- 22315768 TI - Posterolateral corner injuries of the knee--a review. AB - Posterolateral corner injuries of the knee are usually associated with injuries to other structures of the knee. It is not unusual to miss this injury during the initial assessment. Undiagnosed and untreated posterolateral corner knee injury leads to significant morbidity including early osteo-arthritis of the knee. Failure to recognise and reconstruct posterolateral corner injuries is one of the important reasons for the failure of cruciate ligament reconstruction surgery. In this article we have reviewed the literature regarding anatomy, biomechanics, clinical features and treatment of the posterolateral corner injuries of the knee. PMID- 22315769 TI - A short term experience of management of open and osteoporotic intercondylar fractures of the distal humerus using a mini-external fixator. AB - Seven cases of intercondylar fractures of the distal humerus were treated by a mini-external fixation technique. The average range of motion was 30 degrees to 110 degrees. All fractures united with radiologic and clinical evidence of union at 10-12 weeks. Open wound sites healed in 6 cases. There were no evidence of any nerve palsies. PMID- 22315770 TI - Displaced middle-third fractures of the clavicle-operative management. AB - Displaced midclavicular fractures resulting in malunion with shortening and rotational deformity does not remodel in adults and incidence of non-union in displaced midshaft clavicular fractures is between 10-15% especially in those with an initial shortening of >20 mm.We have treated 10 patients of displaced middle-third clavicle fracture by open reduction and internal fixation with plate and screws and found it to be very effective in respect to rehabilitation, union and cosmesis. PMID- 22315771 TI - Percutaneous fixation of displaced intra-articular calcaneal fracture. AB - Operative treatment modalities for calcaneal fracture are still controversial. The outcome of intra-articular calcaneal fracture is mainly influenced by the soft tissue and the subtalar joint. Percutaneous method of internal fixation has been attempted to avoid the problems. Patients with displaced intra-articular calcaneal fracture types IIA, IIB and IIC were treated by initial distraction of subtalar joint, restoration the of subtalar joint, reduction of lateral expansion and finally fixation with screws percutaneously. Twenty-two patients with 26 calcaneal fractures were included. After a mean follow-up of 2 1/2 years and with American Orthopaedic Foot and Ankle Society hind foot score 82 points out of 100. Percutaneous fixation of calcaneum fracture is good alternative method in types IIA, IIB and IIC and selective type III fractures. PMID- 22315772 TI - An evaluation of flexible intramedullary nail fixation in femoral shaft fractures in paediatric age group. AB - Sixty-two femoral shaft fractures in 60 patients treated by elastic intramedullary nailing with mean age of the patients being 9.2 years (range 5 years to 12 years) and average follow-up of 15 months (range 7 months to 60 months) are evaluated. Twenty-eight fractures were fixed with titanium elastic nail while 34 fractures were fixed with Enders nail. There were 40 midshaft fractures, 18 proximal femoral and 4 were fractures of distal third. Fracture patterns were transverse in 35, short oblique in 14 cases and 13 were spiral fractures. Mean age of union in this series was 17 weeks (range 12 weeks to 28 weeks). Ten cases had complications, 5 had nail tip irritation, 3 varus or valgus malalignment and 2 had delayed union. In this series, we did not have any non union, refracture, limb length discrepancy or any major infection. The result demonstrates 100% union rate irrespective of the age, weight and height of the patient. Regardless of the site of fracture and their pattern, it united every time with elastic nail fixation. We did not find and mismatch in the results of fractures stabilised with titanium elastic nail with that of elastic stainless steel nail. PMID- 22315773 TI - Operative management of closed intra-articular fractures of distal end of humerus in adults. AB - This is a study of 60 patients with mean age of 30 years having intra-articular fracture of distal humerus of type C (AO classification). We treated these fractures by open reduction and internal fixation through transolecranon approach. Mean duration of operative time with that of injury was 10 days. In all the cases 1st the intracondylar fracture was fixed followed by reconstruction and stabilisation of medial and lateral pillar by 1/3 tubular plate and 3.5 mm dynamic compressent plate (DCP) or recon plate respectively. Minimum follow-up was of 1 year duration with average follow-up of 3 years. We could achieve 100% union with mean range of movement at the and of 1 year was 20 degree to 110 degree. Two fractures had delayed union, 5 patients had skin complications for which extended dressing was required. None of these patients required SSG or secondary suture. PMID- 22315774 TI - Transcervical osteotomy with modified Tupman plate for fracture neck femur--a new concept. AB - Fracture neck femur is still regarded as unsolved fracture especially in non union and in some vertical shear fracture (Powel's 3). Two types of osteotomies Mcmurry and Shanz valgus osteotomy are suggested, both have some disadvantages. In this context, a transcervical osteotomy has been studied. Twenty-three patients have been studied in all. Transcervical osteotomy has been done and fixed with modified Tupman plate. Patients were allowed full weight bearing after 3 months. Maximum follow-up was of 4 years. According to Salvati and Wilson system all patients graded as excellent to good. It is concluded that transcervical osteotomy may be regarded as a viable option for fracture neck femur. PMID- 22315775 TI - Endometrial aspiration cytology by various techniques. AB - The demand for testing endometrium for detecting pathological as well as hormonal status is increasing and cytodiagnosis is extended very rapidly in malignant and non-malignant conditions. The gynaecologists have responded to this trend by providing cost effective care without compromising the quality. With this in mind, uterine aspiration curettage, ambulatory procedure, for endometrial sampling was studied. Dilatation and curettage (D&C) is probably most commonly performed gynaecological surgery. It accounts for large proportion of hospital bed use and operating room time, the cost is significant and patient also risks the complication of anaesthesia. Consequently various alternative procedures for endometrial sampling like endometrial brush, uterine lavage, jet wash vabra aspiration and endometrial biopsy have been reported. PMID- 22315776 TI - A study of the association of micro-albuminuria and C-reactive protein (CRP) in normotensive diabetic and hypertensive diabetic patients. AB - Diabetes mellitus and hypentension are known to increase markers of inflammation, ie, C-reactive protein (CRP), especially when they develop micro-albuminuria. A total of 60 patients (23 males and 37 females), all having diabetes mellitus, according to ADA criteria and micro-albuminuria in morning spot urine sample were recruited in the study. They were randomised into 2 groups, each comprising 30 patients. Group A comprised hypertensive and Group B normotensive individuals. CRP level was assessed in all patients by routine assay. CRP value of >3 mg/l was observed in 56.66% patients of group A and 23.33% patients of group B (p=0.018). So diabetic patients with micro-albuminuria had more frequent association with increased marker of inflammation in the hypertensive group compared to those without hypertension. PMID- 22315777 TI - Subanaesthetic dose of ketamine in intractable asthma. AB - A 75-year-old male diagnosed to be a case of intractable asthma resistant to all conventional therapies requiring ventilatory support, was successfully weaned off the ventilator after treatment with subanaesthetic dose of intravenous ketamine. PMID- 22315778 TI - Rare association of retinitis pigmentosa and Marfan's syndrome--a case report. AB - A 25 years old male patient presented with long stature with disproportionately long limbs and digits (arachnodactyly). Examination of cardiovascular system showed mitral regurgitation and dilatation of aortic root. Slit lamp examination showed bilateral superotemporal dislocation of lens. Ophthalmoscopy revealed waxy pallor of optic disc, arteriolar attenuation and bone-spicule like pigments in the retina. The diagnosis of retinitis pigmentosa was confirmed by electroretinogram. PMID- 22315779 TI - Femoral pseudoaneurysm in drug addicts: Hunterian ligation still a gold standard. AB - Pseudoaneurysm formation in the site of Intravenous drug abuser had been reported in literature. The repeated puncture of femoral vessels leads to abscess formation and epithelisation of the wall which leads to pseudoaneurysm formation. A case of lacking pseudoaneurysm presenting as reptured groin abscess in a drug addict is reported, which was managed successfully by Hunterian ligation with salvage of lower limb. PMID- 22315780 TI - Laparoscopic repair of late presenting congenital Bochdalek diaphragmatic hernia. AB - Bochdalek diaphragmatic hernia is a common congenital anomaly presenting in the neonatal period and managed by open surgical procedures. Late presentation is usually associated with better prognosis. Here a case of a 10 years old boy presenting with Bochdalek hernia, managed primarily by laparoscopic approach is reported. PMID- 22315781 TI - Septic peritonitis in undiagnosed abdominal pregnancy with foetal death. PMID- 22315783 TI - 2011 Franklin Award presented to Memorial Hermann Healthcare System. PMID- 22315782 TI - Prevention of obstetric anaesthesia-related maternal mortality. PMID- 22315784 TI - Directory of free tools available to accredited organizations. PMID- 22315785 TI - Correction: Standard MM.05.01.09, EPs 7 through 9. PMID- 22315786 TI - Clarification: Safe use of scribes in clinical settings. PMID- 22315788 TI - New animated Speak Up video series: an interview with its stars. PMID- 22315787 TI - Joint Commission pledges support for partnership for patients. PMID- 22315789 TI - New primary care medical home option for accredited ambulatory care organizations: patient-centeredness and care coordination key to new model. PMID- 22315790 TI - Approved: New standard regarding credentialing and privileging requirements for licensed independent practitioners in long term care. PMID- 22315791 TI - Correction: Measure of success requirements for health care staffing services certification. PMID- 22315792 TI - Approved: New infection-related National Patient Safety Goal for 2012: catheter associated urinary tract infections pose high risk. PMID- 22315793 TI - Approved: Seven-day short notice of survey for accreditation in freestanding in vitro fertilization laboratories. PMID- 22315794 TI - Approved: Revisions to the review and appeal procedures for adverse decisions. PMID- 22315795 TI - Approved: New hospital standard sets performance expectations for ORYX accountability measures. PMID- 22315796 TI - Accepted: Revisions to hospital and critical access hospital standards for patient visitation rights: changes made to match updated conditions of participation. PMID- 22315797 TI - Approved: New behavioral health care standards addressing primary physical health care. PMID- 22315798 TI - Approved: New and revised behavioral health care standards addressing medical histories and physical examinations. PMID- 22315799 TI - New palliative care certification program available for hospitals. PMID- 22315800 TI - Approved: New method to record an immediate threat to health or safety situation. PMID- 22315801 TI - Center for Transforming Healthcare aims to reduce the risk of wrong site surgery. PMID- 22315802 TI - Accepted: Updated fire protection systems requirements for critical access hospitals. PMID- 22315803 TI - Approved: 2012 accreditation and certification decision rules. PMID- 22315804 TI - Two hundred years of the curious birth of a doctor--James Barry aka Margaret Ann Bulkley. PMID- 22315805 TI - Calotropis procera root extracts block VEGF-induced angiogenesis: quantitative analysis. AB - Angiogenesis is controlled by number of growth factors, including vascular endothelial growth factor (VEGF). Plant derived anti-angiogenic molecules acting via VEGF are being investigated for curtailing angiogenesis dependent diseases. In this study, methanolic (CM), n-hexane (CH), ethylacetate (CE) and water (CW) extracts of the roots of Calotropis procera were tested for anti-angiogenic activity. In the chicken egg chorioallantoic membrane (CAM) assay, CM, CH and CE but not CW inhibited VEGF-induced neovascularization in a dose-dependent manner. Of all the tested extracts, CM at the dose of 10, 5 and 2.5 ng most effectively inhibited over 83, 71 and 64%, of neovascularization induced by 10ng of VEGF, respectively. Sponge implantation assay in mice further showed that at the dose of 100ng CM, CH and CE but not CW significantly inhibited neovascularization induced by VEGF (100 ng). Taken together, this study indicates that the root extracts of C. procera may possess anti-angiogenic activity. PMID- 22315806 TI - Evaluation of antiinflammatory and analgesic activities of alcoholic extract of Kaempferia galanga in rats. AB - Alcoholic extract of Kaempferia galanga was tested for analgesic and antiinflammatory activities in animal models. Three doses, 300 mg/kg, 600 mg/kg and 1200 mg/kg of the plant extract prepared as a suspension in 2 ml of 2% gum acacia were used. Acute and sub acute inflammatory activities were studied in rats by carrageenan induced paw edema and cotton pellet induced granuloma models respectively. In both models, the standard drug used was aspirin 100 mg/kg. Two doses 600 mg/kg and 1200 mg/kg of plant extract exhibited significant (P<0.001) antiinflammatory activity in carrageenan model and cotton pellet granuloma model in comparison to control. Analgesic activity was studied in rats using hot plate and tail-flick models. Codeine 5 mg/kg and vehicle served as standard and control respectively. The two doses of plant extract exhibited significant analgesic activity in tail flick model (P<0.001) and hot plate model (P<0.001) in comparison to control. In conclusion K. galanga possesses antiinflammatory and analgesic activities. PMID- 22315807 TI - Autonomic status and pain profile in patients of chronic low back pain and following electro acupuncture therapy: a randomized control trial. AB - Pain is a syndrome characterized by several neurophysiological changes including that of the autonomic nervous system. Chronic low back pain (LBP) is a major health problem and is a frequent reason for using unconventional therapies especially acupuncture. This study was conducted to evaluate the autonomic status and pain profile in chronic LBP patients and to observe the effect of electro acupuncture therapy. Chronic LBP patients (n=60) were recruited from the Department of Orthopaedics, GTB Hospital, Delhi. Age and sex matched healthy volunteers were selected as controls (n=30). Following a written consent, LBP patients were randomly allocated into two study groups - Group A received 10 sittings of electro acupuncture, on alternate days, at GB and UB points selected for back pain, while the Group B received a conventional drug therapy in the form of oral Valdecoxib together with supervised physiotherapy. Controls were assessed once while the patients were assessed twice, before and after completion of the treatment program (3 weeks). The autonomic status was studied with non-invasive cardiovascular autonomic function tests which included E: I ratio, 30:15 ratio, postural challenge test and sustained handgrip test. Pain intensity was measured with the visual analogue scale (VAS) and the global perceived effect (GPE). Statistical analysis was performed using repeated measure's ANOVA with Tukey's test. Pain patients showed a significantly reduced vagal tone and increased sympathetic activity as compared to the controls (P<0.05 to P<0.001 in different variables). Following treatment, both the study groups showed a reduction in vagal tone together with a decrease in the sympathetic activity. There was also a considerable relief of pain in both groups, however, the acupuncture group showed a better response (P<0.01). We conclude that there is autonomic dysfunction in chronic LBP patients. Acupuncture effectively relieves the pain and improves the autonomic status and hence can be used as an alternative/additive treatment modality in these cases. PMID- 22315808 TI - Correlation of anthropometric parameters with QTc interval in malnourished children. AB - Various studies have reported the effect of severe malnutrition on electrolyte levels and electrocardiographic parameters. However, only a few have reported these findings in mild and moderate grades of malnutrition in children. Therefore, the objective of this study was to assess the effect of malnutrition (mainly mild and moderate grades) on corrected QT interval (QTc) and QT dispersion (QTcd) and electrolyte changes. A total of 20 malnourished children in the age group of 2-11 yrs were enrolled in the study group and 20 age and sex matched healthy children were taken as controls. Anthropometry, serum levels of albumin & electrolytes were determined. QTc and QTcd (difference between maximum & minimum corrected QT interval) were measured with the help of RMS Polyrite D. Our results have shown that body weight, height, body mass index (BMI), serum levels of albumin, potassium & calcium were lower (P<0.01) in malnourished children. QTc (P<0.01) & QTcd (P<0.01) were significantly greater in malnourished children than controls. We concluded that increase in QTc and QTcd intervals is associated with electrolyte disturbances in malnourished children. Electrolyte disturbance correction and appropriate nutrition therapy followed by further cardiac evaluation must be taken into account in the management of these patients. PMID- 22315809 TI - A comparative study of brainstem auditory evoked potentials in preterm and full term infants. AB - BACKGROUND: Preterm infants can have many neurological problems. An enormous amount of fetal brain development occurs during the last trimester of pregnancy. They include myelination, glial cell migration and the development of a complex gyral pattern. The brain doesn't show the normal growth after birth in preterm infants. Brainstem auditory evoked potentials (BAEPs) are a noninvasive neurophysiologic assessment of brainstem maturation in babies. METHODS: BAEPs in 25 preterm and 25 full-term infants were considered for the study. Infants having history of birth trauma, metabolic disorders or intracranial infection were excluded. BAEP waveforms (absolute and interpeak latencies) were recorded and analyzed. Student t test was used to analyze the data thus acquired. RESULTS: Analysis of data revealed a significant increase in latency of BAEP waveform V (P<0.05). Other latencies and interpeak latencies of BAEP waveforms were comparable. CONCLUSION: The preterm infants have a prolonged latency of BAEP waveform V suggestive of a retarded myelination of the central auditory pathway. Thus BAEP could be a useful electrophysiological test to assess neuronal myelination and maturation in preterm infants. PMID- 22315810 TI - Effect of iron deficiency anemia on audiovisual reaction time in adolescent girls. AB - Adolescent girls are at high risk of developing iron deficiency because of increased iron demands during puberty, menstrual losses, and limited dietary iron intake. This study was carried out to demonstrate the effects of Iron Deficiency Anemia on Audiovisual reaction time in adolescent girls. Adolescent girls between 17-19 years of age with similar socioeconomic background were recruited from college of nursing for the study. They were all screened and categorized into two groups depending on their haemoglobin status. Students having Hb > 12 gm/dl formed the control group i.e. Group I (n=30). All students having Hb < 12 gm/dl and S. Ferritin < 12 microg/dl formed group II i.e. iron deficient anemic (IDA) group. The following haematological parameters were studied Hemoglobin (Hb), MCV, MCH, MCHC (using Sysmex kx-21 Autoanalyser), Serum.Iron, TIBC (Spectrophotometry), Serum.Ferritin (ELISA). Auditory and Visual reaction time were measured by reaction time instrument supplied by Medicaid system, chandigarh. The mean Hb levels in Group I was 12.93 +/- 0.86 and Group II was 10.08 +/- 0.51 (P<0.001). The MCV, MCH, MCHC, S. Iron, S. Ferritin was also significantly less in group II as compared to group I (P<0.001). TIBC was significantly more in group II as compared to group I (P<0.001). Results showed that both ART and VRT were significantly increased (P<0.001) in iron deficient adolescents suggesting a deterioration in sensorimotor performance in anemics. PMID- 22315811 TI - Pulmonary functions in plastic factory workers: a preliminary study. AB - Exposure to long term air pollution in the work environment may result in decreased lung functions and various other health problems. A significant occupational hazard to lung functions is experienced by plastic factory workers. The present study is planned to assess the pulmonary functions of workers in the plastic factory where recycling of pastic material was done. These workers were constantly exposed to fumes of various chemicals throughout the day. Thirty one workers of plastic factory were assessed for their pulmonary functions. Parameters were compared with 31 age and sex matched controls not exposed to the same environment. The pulmonary function tests were done using Sibelmed Datospir 120 B portable spirometer. A significant decrease in most of the flow rates (MEF 25%, MEF 50%, MEF 75% and FEF 25-75%) and most of the lung volumes and capacities (FVC, FEV1, VC, TV, ERV, MVV) were observed in the workers. Smoking and duration of exposure were not affecting the lung functions as the non smokers also showed a similar decrement in pulmonary functions. Similarly the workers working for less than 5 years also had decrement in pulmonary functions indicating that their lungs are being affected even if they have worked for one year. Exposure to the organic dust in the work environment should be controlled by adequate engineering measures, complemented by effective personal respiratory protection. PMID- 22315812 TI - Variability in serum electrolytes in different grades of depression. AB - The present study was planned to assess the variation in serum electrolytes in patients of major depression. A total of 100 patients of 35-45 yrs of age (68 males and 32 females) of depression were compared with the age matched healthy volunteers. Severity of depression was assessed by DSM IV criteria and were graded into mild, moderate and severe depression. In all the subjects serum electrolytes (Na+, K+, Mg++ and Ca++) were assessed quantitatively. All the depression patients were having higher level of Na+, K+, and Ca++ and lower level of Mg++. Multivariate analysis showed that different grades of depression influences statistically significantly levels of serum Mg++ and Ca++ (F(2,98) for Mg++ = 4.88, P value = 0.001 and F(2,98) for Ca++ = 5.97, P value = 0.004). No statistically significant difference was observed for Na+ and K+ although their values were higher (within normal limit) in comparison to that of control group. Multiple comparison revealed highly statistically significant difference between the levels of serum Ca and Mg individually between mild and moderate depression (S V(mild & mod) for Ca++; Mg++ = 7.1; 7.4) moderate & severe depression (SV(mod & severe) for Ca++; Mg++ = 6.82; 6.92) and mild & severe depression patients (SV(mild & severe) for Ca++; Mg++ = 7.46; 7.73) with critical value = 6.36. These results indicated the disbalance in the level of serum electrolytes especially of Ca and Mg in accordance with the severity of depression. PMID- 22315813 TI - Lipid peroxidation and antioxidant vitamin status in colorectal cancer patients. AB - Reactive Oxygen Species (ROS) can induce carcinogenesis via DMA injury. Both enzymatic and non-enzymatic antioxidants participate in cell protection against harmful influence of oxidative stress. The aim of the present study was to assess the level of end product of lipid peroxidation such as malondialdehyde (MDA) as an oxidant in colorectal cancer. Moreover, we analyzed the activity of main non enzymatic antioxidants, vitamin E and vitamin C in colorectal cancer patients. In the present study, total 48 samples were analyzed which includes 24 age matched healthy controls irrespective of sex (Group I) and 24 cases of colorectal cancer (Group II). The serum level of lipid peroxide, vitamin E and vitamin C were estimated in both healthy control Group I (n=24) and colorectal cancer Group II (n=24). A significant increase in the level of serum lipid peroxide (P<0.001), with concomitant decrease in the levels of serum vitamin E and vitamin C, (P<0.001) in Group II patients were noticed as compared to the healthy control Group I. Our findings suggest that increased oxidative stress and reduced antioxidants defense mechanism may play an important role in progression and pathogenesis of colorectal cancer. PMID- 22315814 TI - Comparison of different methods to estimate BMR in adoloscent student population. AB - There is a growing clinical emphasis for the measurement of BMR and energy expenditure in clinical and research investigation such as obesity, exercise, cancer, under-nutrition, trauma and infections. Hence, there is a motivation towards calculating basal metabolic rate using standard equations. The objective of the present work is to identify an appropriate equation in Indian environment for the estimation of calorie needs and basal metabolic rate using the measured height, weight, age and skin fold parameters of an individual. Basal metabolic rates of adolescent male and female population aged between 17-20 years were estimated using equations proposed by FAO, ICMR, Cunningham, Harris Benedict, Fredrix and Miffin. Calorie needs were calculated using factorial approach which involves the multiplication of basal metabolic rate with appropriate physical activity factor. Basal metabolic rates estimated by FAO, Cunningham, Harris Benedict, Fredrix and Miffin are reduced by 5%. These reduced basal metabolic rates and calorie needs are compared with that obtained by Cunningham's equation which is considered as accurate equation. Comparison of the basal metabolic rates and calorie needs obtained by Cunningham equation with all equations such as Harris-Benedict, FAO, Fredrix and Miffin after 5% reduction and ICMR equation without reduction indicates that Harris-Benedict, Fredrix, Miffin and FAO equations can be used for male and female adolescent populations for Indian environment. In conclusion, Harris-Benedict equation is an appropriate equation for both male and female adolescent population for Indian environment. PMID- 22315815 TI - Study of lung functions in smokers and non-smokers in rural India. AB - Smoking is a common habit prevalent in both the urban and rural areas in India. Smoking is a well-known risk factor for chronic obstructive pulmonary disease (COPD), a group of lung diseases that includes emphysema and chronic bronchitis. Pulmonary-function tests provide objective, quantifiable measures of lung function. The objective of the present study was to study and compare the pulmonary function tests among smokers and non-smokers in a rural area, to study the role of possible associated factors and relation of type, quantity and duration of smoking on the pulmonary function tests in Rural Maharashtra. The pulmonary function tests were assessed on computerized spirometer in 400 male subjects comprising of 200 smokers and 200 non smokers. Almost all the pulmonary function parameters were significantly reduced in smokers, more commonly in those aged 50 years and above. Obstructive pulmonary impairment was commonest among smokers. Thus by spirometry a spectrum of lung disorders may be detected at an early stage and subsequent morbidity can be minimized. PMID- 22315816 TI - Immediate effect of nostril breathing on memory performance. AB - The self-control study on thirty normal subjects of both genders (mean age 25.83 +/- 3.41 years) were taken in a self control study group and were tested for three types of Nostril breathing practices and Breath Awareness (BA) effects. Namely verbal recall performance of numerical data such as Digit Span Forward (DSF) and Digit Span Backward (DSB) as well associate learning memory function using Wechsler Memory Scale. The interventions included Right Nostril Breathing (RNB), Left Nostril Breathing (LNB), Alternate Nostril Breathing (ANB) and Breathe Awareness for duration of 30 minutes daily, four consecutive days. The Repeated Measure ANOVA analysis revealed a significant increase in both DSF and DSB recall performance due to RNB at P<0.001 level and increased DSB score due to ANB at P<0.014 level with a non- significant increase due to LNB suggests that the RNB facilitates both DSF and DBF recall performance. However, the LNB effect on left hemisphere helps to restore the memory function of right hemisphere. This study concludes that the RNB enhances numerical data retrieval mostly as a result of left brain activation. PMID- 22315817 TI - Decrease in cardiovascular parasympathetic function tests a decade earlier in females. PMID- 22315818 TI - Temporal dynamics of Trichodesmium erythraeum (Cyanophyta) in the National Park "Sistema Arrecifal Veracruzano" in the Gulf of Mexico. AB - Trichodesmium erythraeum Ehrenberg ex Gomont is a microalga worldwide distributed in tropical seas. This filamentous microalga was detected in phytoplankton samples collected in the Protected NaturalArea "Parque Nacional SistemaArrecifal Veracruzano", and because of its ecological importance, its temporal dynamics was studied using net samples (30 microm) collected in one year period. Samples were studied with a light microscope recording the presence, morphological characteristics, life form and relative abundance. Trichodesmium erythraeum occurred as single filaments and was rare in April 2007 and March 2008; as single filaments from May to August and December 2007; as single filaments and small aggregates in September 2007 and January 2008; in aggregates of large size (> 3mm) and high relative abundance in October 2007; and was absence in November 2007 and April 2008. Although the relative abundance of the species was not important comparing with other members of phytoplankton, its occurrence was frequent with a bloom at the beginning of the north winds period. The observed temporal dynamics of this microalga in this coral reef region comes up on the alert in the monitoring red tides programs being implemented in Veracruz coast. PMID- 22315819 TI - Chaetognatha in the Bahia Magdalena lagoon complex, Baja California Sur, Mexico: species composition and assemblages. AB - The chaetognaths from 187 zooplankton samples collected from the Bahia Magdalena lagoon complex, Baja California Sur, Mexico during March, June, July, August, September, November, and December 1982 were studied. Twelve species belonging to two genera were identified. Sagitta euneritica and S. enflata were the most abundant and most frequent species with maximum abundance in July (40,000 org/100 m(3) and 6100 org/100 m(3) respectively). Sagitta pacifica, S. regularis and S. pseudoserratodentata were stenothermic (21 to 25 degrees C), whereas the rest of the species were eurythermic (15.5 to 29.5 degrees C). Sagitta euneritica contributed considerably to the zooplanktonic biomass, increasing the density in particular in BahiaAlmejas. The analysis of the species assemblages (Morisita index) showed that S. pacifica and S. regularis interact more frequently in August when there is a change of the water masses that converge in this zone during summer, when the California Countercurrent predominates. The composition of taxa during winter is characterized by the dominance of S. euneritica. Entering the warm period, an abrupt change occurs in taxa composition of the three zones studied: channels, Bahia Magdalena, and BahiaAlmejas. The amplitude and distribution of S. peruviana was influenced possibility by the oceanographic conditions of ENSO 1982. PMID- 22315820 TI - Freeze survival of the cyanobacteria Microcoleus chthonoplastes without cryoprotector. AB - A Microcoleus chthonoplastes strain SC7B9002-1 isolated from microbial mats in tidal channels from San Carlos, Baja California Sur, Mexico was subjected to short- (15 days) and long-term (2 years) conservation assays in liquid nitrogen ( 196 degrees C) using cryoprotective agents, such as 5% DMSO, 20% PVP-40, and 20% glycerol. Survival rate, chlorophyll a, protein, and nucleic acids content were observed in each case. Interesting growth and a significant increase in protein content was observed when no cryoprotectant was used during liquid nitrogen immersion. In the absence of a cryoprotectant, M. chthonoplastes lost their typical shape resembled spheroplasts, and recovery cultivation times after freezing were 5 and 25 days (short and long-term, respectively). Recovery from long-term preservation with 5% DMSO took 15 days. PVP and glycerol did not allow recovery of viable cells. The survival of M. chthonoplastes to freezing without cryoprotectant and the adaptive mechanisms that allow surviving under freezing conditions are discussed. PMID- 22315821 TI - Impact of harmful algal blooms on wild and cultured animals in the Gulf of California. AB - Historical documents and classic works together with recent specialized literature have described Harmful Algal Blooms (HABs) in the Gulf of California. This is a review of HABs impact (qualitative and quantitative) during the last decades in the Gulf of California on wild (mammals, birds, fishes, and invertebrates) and cultured animals (shrimps and fishes). Microalgal species responsible of noxious effects are Noctiluca scintillans, Cochlodinium polykrikoides, Gymnodinium catenatum, Prorocentrum minimum, Akashiwo sanguinea, Chattonella subsalsa Ch. marina, Chattonella sp., Heterocapsa sp., Dinophysis sp., Fibrocapsa japonica, Heterosigma akashiwo, Thalassiosira sp., Chaetoceros spp., Pseudo-nitzschia australis, P fraudulenta, Pseudo-nitzschia sp., Trichodesmium erythraeum and ScSchizotrix calcicola. Emphasis is given to the necessity to continue with interdisciplinary studies in oceanography, ecology, toxicology and toxinology interrelated with biomedical sciences such as physiology, pathology, epidemiology and animal health. PMID- 22315822 TI - Ecological composition and distribution of the diatoms from the Laguna Superior, Oaxaca, Mexico. AB - A taxonomic study of diatoms was carried out in a tropical coastal lagoon. Material for this study consists of water samples obtained from February-March 1992 to November-December 2000. Qualitative and quantitative analyses showed the presence of 373 taxa of which the families Bacillariaceae (67 species) and Chaetocerotaceae (37 species) were the most abundant groups. The species Skeletonema costatum, Chaetoceros curvisetus, Coscinodiscus radiatus var. radiatus, Ditylum brightwellii, Thalassiosira eccentrica and Entomoneis alata were found associated with moderate water quality and forming blooms. In addition, a regional comparison between Mexico and South America of the identified species is given. For practical handling, indicative values obtained from their ecological composition are incorporated as well as a code of the floristic list. Achecklist of the species and their occurrence are given. PMID- 22315823 TI - A suggested local regions in the Southern Gulf of Mexico using a diatom database (1979-2002) and oceanic hidrographic features. AB - A diatom data-base of 255 species obtained from 14 oceanographic cruises (14801 entries of 647 sampling sites) together with the analysis of oceanic features were used to establish four local regions in the southern Gulf of Mexico. In addition, common species for each region were designated. This study is based on the application of cluster analysis and the species frequency data. Material for this undertaking consisted of water and net samples obtained between June 1979 and December 2002. Results show that the most frequent species (> 40%) were: Asterionellopsis glacialis, Bacteriastrum delicatulum, B. hyalinum, Chaetoceros affinis, C. coarctatus, C. compresus, C. curvisetus, C. danicus, C. decipiens, C. diversus, C. lorenzianus, C. pelagicus, C. peruvianus, Coscinodiscus radiatus, Cylindrotheca closterium, Guinardia flaccida, Hemiaulus hauckii, H. membranaceus, H. sinensis, Leptocylindrus danicus, Neocalyptrella robusta, Nitzschia bicapitata, Pleurosigma diverse-striatum, Proboscia alata, Pseudo-nitzschia pungens, Pseudosolenia calcar-avis, Rhizosolenia imbricata, R. setigera, Skeletonema costatum, Thalassionema bacillare, T frauenfeldii, T nitzschioides and Thalassiosira eccentrica. The species composition for each region and season are discussed. Itis concluded that sampling site assemblages are related to oceanographic conditions. A total list of species composition is given, forty seven species taxa being new records for this area. PMID- 22315824 TI - The cladoceran trophic status in the nitrogen limited ecosystem of Lake Kinneret (Israel). AB - The impactof cladocerans metabolic activities on the carbon (C), nitrogen (N) and phosphorus (P) dynamics in Lake Kinneret (Israel) is presented. The study, is based on the incorporation of field data and experimental measurements. Grazing, respiration and production rates of Diaphanosoma spp., Ceriodaphnia spp. and Bosmina spp. were experimentally measured at three temperatures, and the results were extrapolated to the field biomass distribution atthese respective temperatures, and the total lake capacity was calculated using the following equation: consumption = respiration + production + excretion. The field capacity of consumption, respiration and production were found to be mostly correlated with biomass density, but the temporal fluctuation of the percent of excretion from consumed energy differed. The increase in P, decline in N and decrease in the TN/TP mass ratio in the epilimnion of Lake Kinneret during 1969-2004 created N limitation. An increase in C and dedine in TN, with a consequential increase in the C/TN ratio were documented. TP was augmented but the C/TP ratio was only slightly increased. During 1975-2004, P was probably, a minor limitation for cladoceran growth. The positive impact of recycled P by cladocerans underthe N limitation in Lake Kinneret is discussed. There is a current threat on the water quality, derived from N limitation (mostly in summer-fall) and consequent Cyanophyta blooms. Thus, the role of recycled P bygrazers may be significant. PMID- 22315825 TI - Trachelomonas (Euglenophyta) from a eutrophic reservoir in Central Mexico. AB - This study provides valuable information on the ultrastructure and environmental conditions of the Trachelomonas Ehr. (Euglenophyceae) genus in the Guadalupe Dam, a eutrophic reservoir located in the suburbs of Mexico City, which receives a considerable volume of wastewaters. Specimens were collected at surface level between November 2005 and May 2006. Using LM and SEM twelve taxa from phytoplankton were identified of which, 9 are new records for Mexico. The reservoir is warm monomictic, with basic pH values (7.4-10.1), a high concentration of chlorophyll a(18-101 microg l(-1), a permanent anoxic bottom, specific conductivity (K25) of 205 to 290 microS cm(-1), N-NO3, 0.19-1.2 mg l(-1) and P-PO4 0.22-1.6 mg l(-1). Water temperature was 15.6-23.0 degrees C. Most of the Trachelomonas species were found during the dry season, when concentrations of organic matter, nitrogen and phosphorus as well as the temperature were the highest. Higher species richness was also associated with the warmer months. This research contributes to increase our knowledge on Trachelomonas in Mexico and constitutes the first detailed description of lorica ultrastructure of 12 taxa that grow in a body of water with high concentration of nutrients and a moderate amount of mineral contents. PMID- 22315826 TI - Seasonal variations in zooplankton abundances in the Iturbide reservoir (Isidro Fabela, State of Mexico, Mexico). AB - This studywas undertaken to quantify the seasonal variations of zooplankton (rotifers, cladocerans and copepods) and selected physico-chemical variables (temperature, pH, conductivity, Secchi disc transparency, dissolved oxygen, ammonia, nitrate and phosphate concentrations) in the Iturbide dam. Monthly zooplankton samples (50 l filtered through 50 microm mesh, in duplicates from each of the 4 stations) were collected from February 2008 to January 2009. Simultaneously physico-chemical variables were measured. The zooplankton samples were fixed in 4% formalin in the field. In general, the temperature ranged from 9 to 16 degrees C, rarely exceeding 20 degrees C. Secchi transparency was nearly 100% since the reservoir was shallow (< 2 m) even during the rainy seasons. Dissolved oxygen was generally high, 13-18 mg l(-1). Nitrate levels (10 to 170 microg l(-1)) were low while phosphates were relatively high (9 to 35 microg l( 1)). The Iturbide reservoir was dominated by rotifer species. We encountered in all, 55 taxa of rotifers, 9 cladocerans and 2 copepods. The rotifer families Trichocercidae and Notommatidae had the highest number of species (7 each) followed by Colurellidae and Lecanidae (6 and 5 species, respectively). Trichocerca elongata, Ascomorpha ovalis, K. americana, K. cochlearis, Lepadella patella and Pompholyx sulcata were the dominant rotifers during the study period. On an annual average, rotifer density ranged between 50-200 ind.(-1). Among crustaceans Chydorus brevilabris and Macrothrix triserialis were most abundant. The maximal density of these cladocerans was about 50 ind. l(-1). Copepods were much lower in numbers (< 20 ind. l(-1)). In general the density of zooplankton was higher during summer months (April to July) than during winter. Shannon Wiener diversity index varied from 1.0 to 4.3 depending on the site and the sampling period. Based on the data of Secchi transparency and nutrient concentrations, the Iturbide reservoir appeared to be mesotrophic. PMID- 22315827 TI - Age effect on the antioxidant activity of Daphnia magna (Anomopoda: Daphniidae): does younger mean more sensitivity? AB - It has been accepted that for most species newborns and senescent organisms are more sensitive than other ages to environmental stressors. Nevertheless, it must be considered that there are several biochemical and physiological compensatory processes which are not expressed with the same magnitude during the whole life cycle. With this aim, Daphnia magna individuals of different age were exposed to hexavalent chromium, Cr (VI), at two different sublethal concentrations (0.032 and 0.0064 mg l(-1)), and the activity of some antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx) were evaluated during most of the life cycle of this cladoceran. The antioxidant enzymatic activity showed an inverse relationship with respect to age. The activity of CAT, GR and GPx were increased in the two treated groups, at all life stages tested. On the other hand, the activity of SOD decreased in the same groups. Both, increase and decrease in the antioxidant enzymatic activities, showed significant differences with respect to the control group, being higher for the 0.032 mg l(-1) group. The Cr (VI) LC50 was also estimated for these age groups, finding statistical differences among them. Even though adults exhibited higher responses, these enzymatic activity changes should not be interpreted as higher sensitivity, since the daphnids acute chromium toxicity followed a different pattern, with increasing LC50 values according to age. PMID- 22315828 TI - Somatic and population growth responses of Ceriodaphnia dubia and Daphnia pulex (Cladocera) to changes in food (Chlorella vulgaris) level and temperature. AB - We quantified the combined effects of three food levels (0.01 x 10(6), 0.1 x 10(6) and 1.0 x 10(6) cells ml(-1)) and three temperature levels (15, 20 and 25 degrees C) on the somatic and the clonal population growth of two cladocerans Ceriodaphnia dubia and Daphnia pulex for 24 to 42 days. The somatic growth data showed that both the cladoceran species began to increase their body size within 3 days and remained stable beyond a week. Food density had a significant effect on the body size of C. dubia while for D. pulex, food level and temperature as well as their interaction had significant effect on the body size. The population growth of both the cladoceran species was affected by temperature. At 15 degrees C, C. dubia showed little growth at the highest food density, while at low food level, there was some increase in the population abundances, especially after a long lag phase of about 2 weeks. At 15 degrees C and under the lowest tested food level, the population of D. pulex did not increase beyond the inoculation density. Optimal population growth of D. pulex was observed at intermediate temperature and at 1.0 x 10(6) cells ml(-1) of food level while for C. dubia 25 degrees C and the highest food level yielded highest growth. At low food level and low temperature, the rate of population increase (r) of C. dubia was much lower than that of D. pulex at comparable conditions. On the hand, at higher food levels and temperature regimes, the r of D. pulex was much higher than that of C.dubia. Regardless of the food levels and temperature, the r of C. dubia varied from 0.03 to 0.07 while that of D. pulex varied from 0.01 to 0.08 day(1). PMID- 22315829 TI - Planktonic ciliates in a hypertrophic pond: functional role and importance. AB - Taxonomical composition and abundance of the planktonic ciliate assemblage in a Lake Tezozomoc, a hypertrophic pond located into an urban park in Mexico City, was investigated along the rainy season (May to October). The aims of the study were to know the main trophic roles and ecological significance of ciliates in a highly productive environment. A low number of taxa (27) and a wide abundance fluctuation (104-387 cil ml(-1)) were found. The most abundant species (up to 162 cil ml(-1)) was Halteria grandinella, an oligotrich ciliate that graze on bacteria and picoplankton, but also several big body sized species that feed on pico and nanoplankton were abundant. Sudden temporal changes in species dominance occurred. Ciliate biomass was very high and fluctuated widely (1.6-88 10(6) microm(3) ml(-1)) being dominated by the >50 microm size fraction that mainly included the pico and nanoplankton feeders. Ciliates are a very important component in the plankton of hypertrophic lakes and their main control factor seems to be the grazing by big-body size Daphnia species. PMID- 22315830 TI - Elaphoidella grandidieri (Harpacticoida: Copepoda): demographic characteristics and possible use as live prey in aquaculture. AB - In freshwater ecosystems, rotifers and cladocerans are ideal prey for fish larvae whereas copepods, due to their purported low growth rate and predatory tendency, are not. We recently isolated the parthenogenetic Elaphoidella grandidieri (Gueme et Richard, 1893) a benthic freshwater harpacticoid, from a fish farm in the State of Morelos, central Mexico and tested its potential as a live prey organism for larval vertebrates. Population growth and life table demography experiments were conducted, in 100 ml recipients with 50 ml of test medium on a diet of Scenedesmus acutus at a density of 1.0 X 10(6) cell ml(-1); the former on live algae alone while the latter on live algae as well as detritus. We also conducted experiments to document the prey preference for this copepod by the larval Ameca splendens (Pisces: Goodeidae) and Ambystoma mexicanum (Amphibia: Ambystomatidae), fed the rotifer Plationus patulus, the ostracod Heterocypris incongruens, and the cladocerans Moina macrocopa and Daphnia pulex. Elaphoidella grandidieri is relatively easy to maintain under laboratory conditions, reaching densities (copepodites and adults) of more than 10,000 l(-1). The generation time ranged between 30-45 days, depending on the diet. The net reproductive rate was as high as 60 nauplii female(-1) day (1). Population growth rates ranged between 0.03 and 0.11 d(-1), live algae being the superior diet compared to detritus. Both predators showed no preference for E. grandidieri, but in the absence of alternate prey they consumed 80% of the harpacticoids offered. The data have been discussed in relation to the potential of E. grandidierias live food for aquaculture. PMID- 22315831 TI - Population dynamics of the tropical cladoceran Ceriodaphnia rigaudi Richard, 1894 (Crustacea: Anomopoda). Effect of food type and temperature. AB - The knowledge of population effects of food on tropical, filter-feeding cladocerans is scarce because a reduced number of species has been extensively studied. Ceriodaphnia rigaudi Richard 1894, a small-sized cladoceran distributed mainly in tropical and subtropical regions of the world, was studied. The aim of this study was to contribute to the knowledge of the reproductive biology of a poor-known Cladoceran; for this we assessed the effect of feeding and temperature on the reproduction and life cycle of this species. Three microalga species (Pseudokirchneriella subcapitata, Ankistrodesmus falcatus, and Chlorella vulgaris) were supplied as food each at a concentration of 12 mg l(-1) (dry weight, equivalent to 1.3 x 10(6), 0.4 x 10(6) and 1.35 x 10(6) cell m1(-1), respectively, and equivalent to 7.8 microg C ml(-1), at two temperatures (20 and 25 degrees C). We evaluated, among other responses, longevity, total progeny, survival, life expectancy at birth and fecundity. Organisms fed with the microalgae A. falcatus and P subcapitata presented both higher longevity (30.7 +/ 5.91, 26.6 +/- 3.59 days, respectively) and total progeny (45 +/- 13.80, 40.7 +/ 0.66 neonates female (-1) values than those organisms fed C. vulgaris (13.5 +/- 4.63 days and 17.6 +/- 6.19 neonates female (-1), respectively). On the other hand, temperature affected significantly the population parameters of C. rigaudi, recording maximal longevity values (56.1 +/- 9.41 days) at 20 degrees C in organisms fed A. falcatus; however, age at first reproduction and total progeny were negatively affected by this temperature: sexual maturation of the females was delayed until the age of 16 days and the number of neonates produced was smaller (9.8 +/- 3.45 with C. vulgaris; 24.7 +/- 6.01 with P subcapitata, and 35.5 +/- 8.59 neonates female(-1) with A. falcatus). The best reproductive responses for C. rigaudi in this study were obtained with A. falcatus at degrees 25 degrees C. PMID- 22315832 TI - Studies on comparative population growth of some species of the rotifer Lecane (Rotifera). AB - We compared the population growth patterns of 5 species of the rotifer genus Lecane [(L. quadridentata (Ehrenberg, 1830), L. comuta (Muller, 1786), L. papuana (Murray, 1913), L. unguitata (Fadeev, 1925) and L. pyriformis (Daday, 1905)] ranging in adult average body size from 30 to 140 microm. All species were cultured under laboratory conditions for 25-30 days using the green alga Scenedesmus acutus as the exclusive diet, at a density of 1.0 x 10(6) cells ml( 1) at 24 degrees C. Regardless of the species, lecanids reached their peak population densities after 4 weeks. Peak population densities ranged from 15 to 320 ind. ml(-1), depending on body size. There was an inverse curvilinear relation between body lengths and peak population abundances (densities) of the Lecane species. Egg ratios (eggs per female) for the tested species were < 0.6 during the exponential phase but declined to 0.1 (or lower) as the population density increased. The rates of population increase for the lecanids were in general lower(0.10 to 0.21 day (-1)) than other well-studied rotifer species including members of Brachionidae. PMID- 22315833 TI - Doyens of the dawn. PMID- 22315834 TI - Trends to access internet among medical students of a government medical college in West Bengal. AB - The use of computer and information technology is on an escalation. The internet, one of the key developments in this field, provides instant access to latest medical information. The present study was conducted (i) to estimate the extent and purpose of internet usage among undergraduate (UG) and postgraduate (PG) medical students, (ii) to identify factors that encourage the students to use internet for medical information, (iii) to assess the need for incorporating computer education in medical curriculum. A prospective, cross-sectional, questionnaire-based study was conducted on 150 students of Burdwan Medical College and Hospital between June 2009 and December 2009. Majority of the students accessed internet from their home PC (42% UGs and 52% PGs).Common search engines browsed commonly by both UGs and PGs include Google and yahoo. Regarding principles of telemedicine and evidence-based medicine, majority of the PGs are well versed while UGs are not (p-value 0.0001). Almost all students agreed to incorporate computer education in medical curriculum. Primary source of medical information was textbook for UGs (62%) and internet for the PGs (48%). Majority of UGs (48%) used internet as a ready source of information thus saving time while PGs (68%) primarily relied on internet for recent advances in their disciplines. The primary purposes of internet use are educational for both UGs and PGs. The data obtained indicates that majority of the medical students participating in the present study embrace and use internet to access medical information. It also justifies the need to incorporate internet and associated information technology into existing medical curriculum. PMID- 22315835 TI - Quality of care among type 2 diabetes mellitus patients residing in an urban slum of Chennai Corporation -- a community-based cross-sectional study. AB - Despite the high prevalence, serious long term complications and established evidence based guidelines for management of diabetes mellitus the quality of care is still deficient in developed and developing countries. So a study of these factors and their influence on the quality of care is necessary to tackle diabetes in the community. The objectives of the study were to assess the quality of care in type 2 diabetes patients of 35 years and above age group and to identify the factors associated with it. It is a community-based cross-sectional study done among urban slum people of Chennai, in which 323 adults with type 2 diabetes were interviewed in the above said age group. Variables like age, sex, income, duration of diabetes, healthcare delivery of choice, treatment prescribed, compliance to treatment, family history of diabetes, presence of comorbid illnesses and quality of care indicators were studied and appropriate statistical analysis was carried out. Only 26 adults (8%) received good quality of care in this study. The adults who received good quality of care were among male sex (p < 0.005), high income group (p < 0.001), patients with good compliance to treatment (p < 0.001) and those who preferred private health facility for treatment (p < 0.001). The present current study indicates very low quality of care among this community. The management of diabetes in our setting was suboptimal and even the minimum achievable goals were not reached. PMID- 22315836 TI - A study on central corneal thickness and optic disc size in patients with primary open angle glaucoma. AB - The aim of the study was to evaluate a possible relationship between central corneal thickness (CCT) and optic disc area in patients with primary open angle glaucoma (POAG). Patients with POAG and age matched control group underwent routine ocular examination along with optic nerve head evaluation by Stratus optical coherence tomography (OCT) and CCT measurement by ultrasound pachymetry. Pearson's coefficient was calculated in both groups to find out correlation between these two parameters. In this series 90 eyes of 45 control subjects and 94 eyes of 47 POAG patients were studied. In the control group 40% were female, 60% male and among the POAG patients 34% female, 66% male. Mean CCT in control subjects was 566.98 micron (SD = 19.36, n = 90) and in POAG patients was 526.61 micron (SD = 29.93, n = 94). There was a significant difference in two groups (p = 0.0002). Disc area in control group had mean of 2.32mm(2) (SD = 0.305, n = 90) and in POAG group 2.982mm(2) (SD = 0.566, n = 94). Statistically significant difference was found among the two groups (p = 0.0). CCT was inversely correlated with optic disc size. In control subjects, r = -0.141, but it was not statistically significant (p = 0.092). In POAG group, r = -0.256 and the correlation was statistically significant (p = 0.0063). CCT was significantly less in POAG patients compared to control subjects. Mean disc area was significantly higher among the POAG group compared to control subjects. CCT was inversely correlated with disc area in both groups, but was statistically significant in POAG patients. PMID- 22315837 TI - Prevalence and pattern of use of indigenous medicines in diabetic patients attending a tertiary care centre. AB - The aim of the study was to see the pattern of use of indigenous medicines in diabetic patients and to find out its correlation with various demographic variables in patients of type 2 diabetes. A sample of 113 patients with diabetes (type 1 and type 2) was interviewed using a structured questionnaire by trained medical personnel about the intake of indigenous medicines. Correlation of intake of indigenous medicines with various demographic variables was assessed using appropriate statistical tests. Male to female ratio in the present study was 1:3. Mean duration of diabetes was 5.2 +/- 2 years. It was found that majority of patients 101/113 (89.4%) attending diabetic clinic were using indigenous medicines in one form or the other. Most common drugs used were karela (78.8%), jamun (65.5%), methi (38.9%) and neem (28.3%). Majority were taking on advice from fellow diabetics (41.6%) and were not sure (39.8%) about the effect. No significant correlation was found with their intake and demographic variables as age, sex, per capita income, duration of diabtes, occupation, cultural background and antidiabetic medicine used. There is a high percentage of indigenous drug use in patients with diabetes which is often not reported. Treating physicians need to be alert to this possibility while managing diabetic patients in order to correctly interpret glycaemic control, hypoglycaemic episodes and other unexplained comorbidities that might arise in them. PMID- 22315838 TI - Yours faithfully -- prevention of parent to child transmission (PPTCT). AB - The objective of this study is to find out the reasons behind drop out of the mothers from the prevention of parent to child transmission (PPTCT) programme, thereby going undiagnosed of their HIV serostatus. A retrospective 6-year study was undertaken among mothers attending antenatal clinic and the unbooked cases delivering at the medical college. The percentage of mothers taking pretest counselling was 95.19; 94.09 per cent agreed to have their blood tested among those who had registered at the antenatal clinic only. Of them, 33 were found to be seropositive, 12 being found in 2009 alone. But the daily average of unbooked cases delivering at this institution was 16.42 out of 28. And a huge number (58.9%) were unregistered ie, unknown HIV serostatus deliveries were taken place during this 6-year of study (2004-2009). By this study we have found out that our ignorance, work pressure and patients' lack of knowledge, fear of so called 'HIV AIDS', social stigmas are creating the big gaps in PPTCT programme and thus made it unsuccessful. PMID- 22315839 TI - Pseudothrombocytopenia -- a caveat. AB - Pseudothrombocytopenia is an ex vivo thrombocytopenia, counted by an automated cell counter, but not configured by microscopic examination of a well prepared blood smear. Incidences of pseudothrombocytopenia reported in different studies range from 0.09-0.21%, which could account for 15-30% of all cases of thrombocytopenla. Failure to identify pseudothrombocytopenia has led to a lot of clinical problems like unnecessary platelet transfusion, glucocorticoid therapy and so on. Haematological cell counters count platelets as particles with volume between 2 and 20fl. Thus platelet clumps are counted as leucocytes while fragmented RBCs as platelets. This study found pseudothrombocytopenia due to causes like EDTA blood stored at less than 32 degrees C for more than 2 hours (35%), excess EDTA in sample (10.7%), hyperlipidaemia, auto-immune disease, pregnancy, etc. No apparent cause could be found in 52% of cases. Hence it is emphasised that direct microscopic examination of a well stained blood smear from EDTA-venous blood (within 1hour) and or direct counting under Neubauer chamber with 1% ammonium oxalate (in special cases) is almost mandatory before releasing a report of platelet count. Also factors related to ratio and storage of EDTA blood, calibration of instruments, proper selection of reagents, supervision of laboratory staff are essential to rule out any error of report including pseudothrombocytopenia. PMID- 22315840 TI - Barrett's metaplasia in Indian obese male patients with gastro-oesophageal reflux disease. AB - Although 10% to 15% of gastro-oesophageal reflex disease (GERD) patients have Barrett's oesophagus, neither the frequency nor the severity of symptoms correlates with the presence of Barrett's epithelium. Age, male sex, white race, and obesity have been implicated in some studies. The studies in Indian population reflect low prevalence rates; however, there is no study of obesity as independent risk factor for Barrett's disease in Indian population. The present study showed Barrett's oesophagus in 9.5% patients who were obese as compared to non-obese patients having Barrett's 6.7% suggesting obesity might not predispose to Barrett's oesophagus, in patients of GERD taken criterion for obesity as BMI more than 30. PMID- 22315841 TI - Efficacy and safety of magnesium sulphate (MgSO4) in the treatment of eclampsia. AB - Use of magnesium sulphate (MgSO4) in the treatment of eclampsia has not yet become universal probably due to some perceived apprehension about its efficacy and toxicity. This study aimed to assess, in addition to foetomaternal outcome, its efficacy to control fits in eclampsia and toxicity if any. Fit control, occurence of toxicity and foetomaternal outcome were noted in 459 cases of eclampsia treated with MgSO4. MgSO4 was very effective in controlling fits with a very low (1.31%) fit recurrence rate and had an even lower incidence of toxicity (as evidenced by sluggish patellar reflex). None of the cases developed any life threatening toxicity like respiratory paralysis. Maternal mortality rate was 3.70% and perinatal mortality 9.15%. The results suggest that MgSO4 is very safe and effective for treating eclampsia and offers good prognosis for both mother and foetus. PMID- 22315842 TI - Clinical profile and surgical outcome of Meckel's diverticulum. AB - The aim of the study was to estimate the incidence and analyse the clinical profile and surgical outcome of the Meckel's diverticulum. This prospective study included 632 patients who were operated upon for acute abdomen during August 1999 to July 2004 in a single surgical unit. Pre-operative abdominal ultrasonography and plain x-ray abdomen erect were done depending on the necessity. These patients were subjected to laparotomy/appendicectomy depending on the case. A search for Meckel's diverticulum was done and if found, surgical resection and analysis by histopathological confirmation of the Meckel's diverticulum was performed. This study detected 9 patients (1.42%) with Meckel's diverticulum during the operation. In none of these cases pre-operative diagnosis of Meckel's diverticulitis was made. Out of 9 patients, 6 (66.6%) were males, 3 (33.4%) females. Four cases (44.4%) were symptomatic due to Meckel's diverticulum and 5 (55.6%) were asymptomatic. One patient presented with haematochezia, one with intestinal obstruction due to gangrene of the Meckel's diverticulum and one case of duplication of (double) Meckel's diverticulum. Histopathological examination of these specimens confirmed 2 cases with inflammation, one with gangrene and one ulcerated gastric mucosa in the Meckel's diverticulum. In 2 cases (22.2%) there was heterotopic epithelium (gastric-1, colonic-1). It is recommended that a search for Meckel's diverticulum in every case of appendicectomy, laparotomies for acute abdomen should be conducted and if found, Meckel's diverticulectomy/resection should be performed to avoid secondary complications arising from it. PMID- 22315843 TI - Signet ring cells in ascitic fluid -- a diagnostic dilemma. AB - Traditional teaching is that signet ring cells are the hall-mark of ovarian metastatic tumours. Paracentesis done for therapeutic purpose showed these cells and momentarily misled us. Other differentiating data are important in the correct management of cases with signet ring cells found in either ascitic fluid or on histopathologic examination. PMID- 22315844 TI - A rare case of ectopic thoracic kidney and spleen. AB - A 23-year-old male presented with fever of 5 days duration. His peripheral smear was positive for Plasmodium vivax. He was treated for malaria and responded. During investigation with USG it was found that he had absent left kidney. An abdominal contrast enhanced CT scan revealed ectopic kidney and spleen in the left hemithorax. This was a rare case of ectopic thoracic kidney and spleen. PMID- 22315845 TI - A rare case of lung cancer with invasion in the heart giving rise to electrocardiographic features simulating myocardial infarction. AB - Bronchogenic carcinoma commonly metastasises to liver, bone, brain and adrenals. Involvement of mediastinal structures like superior vena cava, recurrent laryngeal nerve, phrenic nerve, pericardium, etc, is also common. But invasion of myocardium is very rare in bronchogenic carcinoma. A rare case of lung cancer with invasion to left atrium and ST segment elevation on electrocardiogram (ECG) mimicking myocardial infarction is presented here. PMID- 22315846 TI - Primary amoebic meningo-encephalitis due to Naegleria fowleri. AB - Primary amoebic meningo-encephalitis is a fulminant, often rapidly fatal infection affecting individuals with a recent history of swimming in warm fresh water. A fatal case of primary amoebic meningoencephalitis due to Naegleria fowleri in a 35 years old male suffering from human immunodeficiency virus with pulmonary tuberculosis infection is reported. Naegleria fowleri was diagnosed by wet mount examination of cerebrospinal fluid and the diagnosis was confirmed by culture of the cerebrospinal fluid on non-nutrient agar layered with Escherichia coli. The patient was treated with amphotericin B and antituberculous treatment but the outcome was fatal. Primary amoebic meningo-encephalitis should be suspected in every case of pyogenic meningo-encephalitis in which no bacteria or fungus is found on cerebrospinal fluid examination. PMID- 22315847 TI - Neonatal genital prolapse. AB - Neonatal genital prolapse is a rare condition, usually associated with congenital spinal defects and is often resistant to simple reduction. A case of complete uterine prolapse which was noted shortly after birth in a female baby with a meningocele at the lumbar region with rectal prolapse is reported. The vagina and uterus was restored to their normal position but came out immediately after reduction. PMID- 22315848 TI - Tuberculous oesophagopleural fistula. AB - Hydropneumothorax complicating to oesophagopleural and broncho-oesophageal fistula is an unusual presentation and is reported in literature as separate clinical entities. Here we present a case of hydropneumothorax with both oesophagopleural and broncho-oesophageal fistula of tuberculous aetiology occurring simultaneously in the same patient. Oesophagopleural fistula was suspected clinically by colour of pleural fluid. Subsequent barium swallow demonstrated leak of contrast material from oesophagus into pleural cavity. Later on, computed tomography of chest with oral contrast confirmed communication of oesophagus with both right pleural cavity and right main bronchus. The fistulous connection between these structures appeared to be due to tuberculous mediastinal lymphadenopathy as evident on CT thorax. PMID- 22315849 TI - A rare case of bilateral tubal pregnancy. AB - Diagnosis of ectopic pregnancy continues to be an important challenge. Here a case of incidental diagnosis of bilateral tubal ectopic pregnancy is reported. There was a ruptured tubal ectopic pregnancy on the left side and chronic ruptured tubal ectopic pregnancy on the right side. Leading cause of first trimester maternal deaths is due to complications of ectopic pregnancy. Here an unusual case of ectopic pregnancy is reported in which the patient had spontaneous bilateral tubal ectopic pregnancy which presented with left tubal rupture and subsequently emergency exploratory laparotomy revealed bilateral tubal mass, which on histopathological examination confirmed tubal pregnancy. PMID- 22315850 TI - Bilateral multicystic dysplastic kidneys -- an unusual case diagnosed on antenatal ultrasound. AB - While it is true that unilateral multicystic dysplastic kidney is commonly associated with abnormalities in the contralateral kidney, it is not widely known that the condition may be bilateral. The recognition of the bilaterality of the multicystic dysplastic kidney by ultrasound has grave prognostic implications as this condition is uniformly fatal. High resolution ultrasound examination of the foetus enables early detection of congenital malformations of the urinary tract. This information is of value in determining foetalprognosis, in deciding the method of delivery, and in alerting the paediatricians to supportive and corrective measures which may need to be taken in postnatal period. PMID- 22315851 TI - Primary cold agglutinin disease. AB - A 4-year-old girl presented with severe pallor and intermittent passage of cola coloured urine. Routine investigations were suggestive of auto-immune haemolytic anaemia. Red cell agglutination was observed in peripheral smear and patient's serum was positive for cold agglutinins. Thorough work-up ruled out secondary cold agglutinin disease. Patient was treated successfully with corticosteroids. PMID- 22315852 TI - Lobular carcinoma breast -- a very atypical clinical and cytological presentation. AB - Lobular carcinoma of breast may present with very atypical clinical features. Atypical signs or symptoms due to metastasis to central nervous system may be the 1st sign of clinical presentation. Here a case of a 30 years old female is reported who presented with features of Bell's palsy progressing to cranial polyneuropathy. On thorough clinical examination she had only a small breast nodule. Magnetic resonance imaging of brain showed erosion of the base of skull. The nodule was aspirated two times, and it came out to be fibro-adenoma until a excision biopsy was done which proved it to be lobular carcinoma. The patient was treated with palliative radiation and she improved considerably measured in terms of adjustment daily life (ADL) score. PMID- 22315853 TI - Giant urethral diverticulum -- repair augmented with bovine pericardium collagen matrix graft and tension-free vaginal tape. AB - A 44-year-old nulliparous woman was diagnosed with a giant urethral diverticulum. Surgical excision of the diverticulum was done. The urethral defect was closed with 2-0 vicryl sutures. A piece of bovine pericardium collagen matrix graft was placed over the fascial repair. A tension-free vaginal tape (TVT) sling was then placed over the graft. Concomitant anti-incontinence procedure can be combined with diverticulum repair. PMID- 22315854 TI - Heteropagus twinning on back -- a case report. AB - Heteropagus twins, also called parasitic twins, are malformation of the foetus where the development of one twin is incomplete. They are attached most commonly to the lower chest and upper abdomen. We report a case of heteropagus twin, where the parasite possessed well-formed limb as well as blind ending intestine. It was attached to the back of the host by a broad pedicle. We take this opportunity to classify areas of confusion prevailing regarding twinning, foetus in foetu, teratoma and caudal duplication. PMID- 22315855 TI - A rare case of giant cutaneous and extracutaneous haemangiomas. PMID- 22315856 TI - Ethically yours ..... PMID- 22315857 TI - Role of scaphoid in the abduction and adduction movements of wrist joint. AB - Being a carpal bone scaphoid has an important role in wrist movements. Wrist joint is a synovial modified ellipsoid joint where movements like flexion, extension and adduction, abduction take place around two axes (transverse and anteroposterior). These movements at the wrist joint are associated with considerable range of movements at the midcarpal joint, as same group of muscles act on both of these joints. A study has been done amongst 120 persons at the Institute of Postgraduate Medical Education and Research, Kolkata, West Bengal during the period from 1998-2000 to detect the important movements of scaphoid bone specially during the abduction and adduction of wrist joint (which occur in association with the intercarpal joints) and also to detect whether such movements have any speciality in the population of eastern part of India. It was found in this study that the scaphoid acts as a link bone between the two rows of carpal bones and prevents the buckling of midcarpal joint specially of the capitato-lunate joint interface. PMID- 22315858 TI - Prevalence and determinants of obesity in the adult population of Kanpur district -- a population-based study. AB - Worldwide, obesity is the most prevalent form of malnutrition. It is one of the most significant contributors to ill health and an indirect cause of morbidity and mortality resulting from hyperlipidaemia and glucose intolerance. Very few studies on the prevalence of obesity have been reported from developing countries like India. The present study was therefore undertaken to determine the prevalence of obesity and its predictors in the Indian community. The objectives are: (1) To determine the prevalence of obesity, (2) to study the relationship of obesity with age, (3) to identify the predictors of obesity. This community-based cross-sectional study was conducted on 801 subjects, aged 20 years and above in Kanpur District, using multistage stratified random sampling technique. Data was analysed using the software statistical package for social sciences 10.0.1 for windows. Prevalence of obesity was found to be 4.7%. An increase in body mass index was seen with increasing age. A higher prevalence of obesity was seen in the urban population and in women. Age, gender and daily intake of saturated fatty acids were found to be the main predictors of the obesity. An increase in the level of physical activity resulted in a decrease in the prevalence of obesity (odd's ratio = 0.36). Obesity is an emerging public health problem in the Indian population which indicates that intervention at the primary healthcare level, especially in diet and activity, are important for its prevention. PMID- 22315859 TI - Diagnostic dilemma of dengue fever: how much reliability are there in rapidity. AB - Rapid diagnosis of dengue infection is essential to patient management and disease control. In a rural tertiary health setting and diagnostic laboratories, dengue suspect cases were assessed with a rapid (15 minutes) immunochromatographic test and compared to an IgM capture enzyme-linked immunosorbent assay (ELISA) (2-3 days) and the reliability of the rapid test was tested. The objectives were to evaluate dengue rapid test against dengue IgM capture ELISA and to assess the scopes of such rapid tests in peripheral setting. A rapid immunochromatographic card test was compared with an IgM capture ELISA (National Institute of Virology, Pune, India) as the reference gold standard. The sensitivity and specificity of the test was compared over a period of five years in a rural tertiary hospital among 158 dengue suspects. The rapid test showed good sensitivity in the diagnosis of both primary and secondary dengue infection. The rapid test as confirmed by IgM capture ELISA was found to have specificity of 98.4% and a sensitivity of 96.4%.The positive predictive value was 93.1% and negative predictive value of 99.2%.The positive likelihood ratio worked out to be 62.6,with negative likelihood ratio was 0.036,signifying large impact. The rapid tests may be useful aid in screening in case of clinical diagnosis of dengue infection,particularly valuable in peripheral health settings,where it can hasten the initiation of firstline of management; while the ELISA has a place in central testing laboratories, aiding in resource optimisation. PMID- 22315860 TI - Study of serum electrolytes in pregnancy induced hypertension. AB - Hypertension complicating pregnancy is an important cause of foetal and maternal mortality and morbidity. Serum sodium, potassium, calcium and magnesium were evaluated in cases with gestational hypertension and pre-eclampsia and compared with normotensive pregnant women of corresponding period of gestation. Taking urinary micro-albumin creatinine ratio as standard to predict pregnancy induced hypertension, the role of serum electrolytes to predict the same was studied. A total of 200 patients were evaluated. There were no change in serum sodium and potassium in gestational hypertensive cases as well as in pre-eclamptic cases when compared with control group. Similar results were obtained when serum calcium level was evaluated. Mean serum magnesium level (1.53 +/- 0.29 mg/dl) was significantly low in cases of pre-eclampsia, while it was 1.79 +/- 0.25 mg/dl in patients with gestational hypertension and 2.19 +/- 0.2 mg/dl in control group. Patients having gestational hypertension along with increased micro-albumin creatinine ratio had significantly low mean magnesium level (1.68 +/- 0.1 mg/dl) when compared with gestational hypertensive patients with normal microalbumin creatinine ratio (serum magnesium level 1.87 +/- 0.1 mg/dl). PMID- 22315861 TI - Managing dyslipidaemia: evolving role of combination therapy. AB - Dyslipidaemia is one of the most important modifiable risk factors for coronary disease. Despite the availability of highly effective lipid-modifying agents, many patients still do not reach lipid targets established by national guidelines. This, in turn, has prompted a resurgence of the search for drugs and algorithms that favourably affect the lipid profile. The preventive efforts made so far have demonstrated that lowering low density lipoprotein-cholestrol is one action that individuals and populations can do with significant success in delaying the onset of clinical events, but at the same time one should not neglect high density lipoprotein and triglyceride levels as they also play a significant role in the risk of developing complications. Combination regimens should be considered for use in patients who fail to meet target values and are compliant with their current therapy. Although the use of combination therapy varies considerably across the globe, this treatment strategy is becoming increasingly more common as treatment guidelines recommend more aggressive therapy in order to achieve lower target cholesterol goals. PMID- 22315862 TI - Management of snakebite cases by national treatment protocol at Jalpaiguri District Hospital in West Bengal in the year 2010--a retrospective study. AB - Snakebite remains a public health problem in India, occurring most frequently in the summer and rainy seasons. Bites are maximal in lower limbs. Victims are typically male and between 17 and 27 years of age. Children and the elderly have higher mortality. The worst affected states are Kerala, Maharashtra, Tamil Nadu, Orissa, Assam and West Bengal. There was no uniform guideline for treatment of snakebite cases. The five common venomous Indian snakes biting humans are common cobra, krait, Russell's viper, saw scaled viper and the hump nose pit viper. Seventy per cent of all snakebites are non-venomous. Even in bites by venomous snakes, envenomation occurs in only 50% of cases. Immobilisation is much more important than tight ligature, which may cause gangrene. Only a minority need antivenom, which is expensive, short in supply and may cause severe reaction. Antivenom treatment is recommended on the basis of local and systemic signs and symptoms and 20 minutes whole blood clotting test (20WBCT). Delay in starting AVS treatment is the main cause of mortality and morbidity. Skin test is of no value. But antivenom should not be used unless specifically indicated. The "Do it RIGHT" approach of national treatment protocol indicates the initial steps to be taken before reaching a hospital or primary healthcare facility. And it resulted in a 66% decline in the amount of ASV administration and an absolute reduction of mortality by 24%. However first aid treatment of the bitten limb/area with broad spectrum antibiotics, injection tetanus antitoxin and Supportive treatment with blood transfusion, ventilatory support, anticholinesterase and peritoneal dialysis may also be required. PMID- 22315863 TI - Subgrouping of A and AB blood groups in Indian blood centres: is it required? AB - Anti A1 antibody in the serum of A2 and A2B individuals is rare but when present can have laboratory and clinical significance. Routine subgrouping of all A and AB blood groups in blood centres in India is difficult due to economic constraints and has always been a point of debate. This study thus brings out the prevalence of anti A1 antibody and the clinical significance related to its presence. The results of the study showed a low prevalence of anti A1 antibody and when present, it had a low thermal amplitude and titre. Further, no blood group discrepancy or problems during compatibility testing were encountered with these (A1 antibody positive) blood units. Thus, it may be concluded that in India and other developing countries where resources are scarce, routine subgrouping of A and AB may not be really worthwhile unless there is a group discrepancy, problem during compatibility testing or history of a transfusion reaction. PMID- 22315864 TI - Prevalence of overweight and hypertension among rural and urban school going children and association of hypertension with overweight. AB - Overweight is a burning problem of school going children especially in affluent society. So urban children are affected more. Hypertension is a major co morbidity of overweight. The number of overweight and hypertensive children is increasing and more among urban children. In this study sample was taken from rural and urban school going children of various age groups. The prevalence of overweight and hypertension among rural and urban school going children was obtained and relation between overweight and hypertension was established. PMID- 22315865 TI - Is this acute lymphoblastic leukaemia or juvenile rheumatoid arthritis. AB - Arthritis could be a presenting feature of acute lymphoblastic leukaemia (ALL) and could be wrongly diagnosed as juvenile rheumatoid arthritis (JRA). Clinical and laboratory parameters might differentiate ALL and JRA in children who present with arthritis. Out of a total of 250 children of ALL, 10 were referred to the department of child health and paediatric haemato-oncology of Christian Medical College, Vellore during 1990-2002. They were compared with 10 age-matched children who had systematic onset of JRA. The age groups in ALL and JRA were 6.05 +/- 2.45 years and 5.47 +/- 4.4 years respectively. Severe pain as evidenced by inability to walk was found in children but one child with JRA was unable to walk (p < 0.05). Lymphocytosis was noticed in 7 children (70%) with ALL whereas none had in JRA group. ESR was elevated in all cases in both the groups. One case in each group had antinuclear antibody positivity. It can be concluded that ALL can masquerade as systematic onset of JRA. So paediatricians should be careful enough while diagnosing the disease process. PMID- 22315866 TI - Stem cell transplantation: brief review and current status. AB - In recent years stem cell has come up as a great advance in therapy for a number of illnesses and has potential for revolutionising the medical field. Right from myelodysplastic syndrome to amyloidosis it has been tried. The present review is a modest endeavour to acquaintain in brief about current status of stem cells. PMID- 22315867 TI - Compulsive buying: an overlooked entity. AB - Compulsive buying is an under-recognised entity among Indian psychiatrists. A Medline search, hand searching of journals and direct communications with lead investigators in compulsive buying have generated numerous studies. Overseas data indicate a community prevalence between 1% and 8% . The phenomenon can be an independent entity or appears as a comorbidity with another axis I or axis II disorder. A degree of suspicion on part of clinician regarding its possible presence is the key to its detection. A few rating instruments are available to quantify the morbidity and screening for compulsive buying. Management involves pharmacotherapy with SSRIs, psychotherapy, self-help groups and self-help books. Epidemiological and clinical studies on compulsive buying should be undertaken by Indian psychiatrists to provide better services for people suffering from compulsive buying. PMID- 22315868 TI - Amniotic membrane transplantation for acute ocular chemical burns in a child. AB - An ocular burn injury with calcium hydroxide with opaque cornea and limbal ischaemia of more than 270 degrees which was treated byamniotic membrane transplantation on the 6th day following injury is reported. Postoperatively the ocular surface remained stable with no inflammation, vascularisation or infection. Amniotic membrane restored conjunctival surface much earlier than corneal surface and prevented symblepharon formation. We believe that amniotic membrane transplantation may be considered in acute phase of severe chemical injury for a more favourable prognosis. PMID- 22315869 TI - Ophthalmomyiasis externa -- report of two cases. AB - Ocular myiasis in humans is a rare phenomenon. Here two cases are reported who came to a tertiary care centre with features of unilateral acute catarrhal conjunctivitis. Fly larvae were detected on slit lamp examination and removed after immobilising it with topical 4% lignocaine. Topical antibiotics and steroid drops were prescribed for 2 weeks. The samples were identified as Oestrous ovis by the entomology department of the Institute of Tropical Medicine, Kolkata. The signs and symptoms regressed within 48 hours. The cases are being reported to create awareness among the ophthalmologists regarding larval conjunctivitis especially in developing countries like India, where the general standard of hygiene is low and fly infestation is common. PMID- 22315870 TI - An unusual presentation of aggressive fibromatosis (retroperitoneal desmoid tumour) in pelvic cavity presented as obstructed labour. AB - Retroperitoneal desmoid tumours are uncommon tumours usually occurring in young females in their reproductive age group and commonly have a benign course but sometimes they can become malignant. These tumours belong to family of myofibroblastic fibromatosis. These tumours are composed of fibroblastic cells with bands of collagen and ill defined cytoplasm and rarely show mitosis. Recurrence is common especially after incomplete excision. Retroperitoneal desmoid is an uncommon tumour among desmoid group which led to an obstructed labour. Here a 28-year-old female diagnosed to have a pelvic desmoid, was missed during the antenatal check-up, presented as an obstructed labour which necessitated a caesarean section. The patient underwent a definitive surgery three months later for excision of tumour. The tumour was excised through a combined abdominal and gluteal incision. Histopathological report revealed an aggressive fibromatosis (retroperitoneal desmoid). PMID- 22315871 TI - Isolated cryptococcal osteomyelitis in immunocompetent patient. AB - Cryptococcosis is a common opportunistic infection in AIDS patients. Almost all cases present with meningitis with or without fungaemia. Cryptococcal osteomyelitis occurs as part of a disseminated infection. Isolated cryptococcal osteomyelitis is rare and more so in immunocompetent patients. A case of isolated osteomyelitis caused by Cryptococcus neoformans in an immunocompetent patient is reported here. A female patient of 60 years old presented with pain and swelling of left clavicle. The histopathological examination of the biopsied material (bony fragment) showed histiocytes, lymphocytes with many foam cells showing organisms, the morphology was consistent with cryptococcus. Fluconazole was advised and she responded favourably. PMID- 22315872 TI - Torsion of undescended testis in an infant: case for early orchiopexy. AB - Torsion of the testis is a true surgical emergency in paediatric age group. Prompt recognition of the condition and immediate surgical intervention is the only hope for testicular salvage. The condition becomes all the more important when this occurs in an undescended testis as the diagnosis is often delayed, and therefore the treatment too. A six-month old infant presented with the torsion of an undescended testis. Even prompt exploration could not avoid the necrosis and orchidectomy was done. Therefore to avoid this almost unsalvageable condition the orchiopexy must be considered at an earlier age. PMID- 22315873 TI - Myasthenia gravis in a one year eight months old female child. PMID- 22315874 TI - FNAC diagnosis of meningioma. PMID- 22315875 TI - A phase III clinical trial of alpha, beta-arteether injection 150 mg/ml in patients of P falciparum malaria. AB - The aim of study was to evaluate efficacy and safety of alpha, beta-arteether injection 150 mg/ml by performing a phase III, multicentre, open label, and single treatment study in patients with P falciparum malaria. A total of 145 patients with P falciparum malaria were screened to achieve patient pool of 101 subjects based on inclusion and exclusion criteria, from which 100 patients completed the study successfully. Mean cure rate was calculated as primary efficacy parameter, while mean parasite clearance time (hours) and mean fever clearance time (hours) were calculated as secondary efficacy parameters, to evaluate efficacy of alpha, beta-arteether injection 150 mg/ml. Safety evaluation was measured by observing and monitoring adverse events, clinical examination, assessment of vitals and haematology laboratory parameters. Statistical analysis was performed with 5% level of significance. Mean cure rate, mean parasite clearance time (hours) and mean fever clearance time (hours) were 99.01%, 24.72 +/- 0.41 hours and 46.86 +/- 0.97 hours respectively. A total of 6 patients were observed with pain at injection site out of 101 enrolled patients. There were no clinically significant vitals and haematology changes. There were no abnormal posttreatment values observed. The study confirmed that alpha, gamma-arteether injection 150 mg/ml is highly effective in treatment of P falciparum malaria. PMID- 22315876 TI - Looking forward. Medical liability reform. PMID- 22315877 TI - Medical liability reform: evidence for legislative and alternative approaches. PMID- 22315878 TI - Sanctity and organ donation's societal value. PMID- 22315879 TI - Sanctity and organ donation's societal value in an opt-out country: the Austrian experience. PMID- 22315880 TI - CPT 2012 brings with it new codes and code changes. PMID- 22315881 TI - HPRI data tracks. Urology workforce trends. PMID- 22315882 TI - 2011 lobby day wrap-up: Ohio, Massachusetts, and Alabama. PMID- 22315883 TI - A look at The Joint Commission: new standard for surgical accountability measures. PMID- 22315884 TI - Looking forward. PMID- 22315885 TI - PQRS reporting of venous thromboembolism prophylaxis. PMID- 22315886 TI - Incentive payments for operations furnished in HPSAs. PMID- 22315887 TI - Surgeons, other providers take the lead on integrating health care services. PMID- 22315888 TI - The USS George Washington medical department: medicine in motion. PMID- 22315889 TI - The quest for significance. PMID- 22315890 TI - Operation Hernia in Carpenter, Northern Ghana. PMID- 22315891 TI - Statement on the physician acting as an expert witness. PMID- 22315892 TI - E/M coding can be easier than one might think. PMID- 22315893 TI - Navigating the legislative process. PMID- 22315894 TI - A look at The Joint Commission: engaging physicians in hand hygiene challenges. PMID- 22315895 TI - Looking forward. Comparative effectiveness. PMID- 22315896 TI - Using social media to enhance surgeon and patient education and communication. PMID- 22315897 TI - Beyond volunteerism: augmenting surgical care in resource-limited settings. PMID- 22315898 TI - The state of medical liability reform. PMID- 22315899 TI - Covering patients through insurance mandates. PMID- 22315900 TI - HPRI data tracks. Developing an index of surgical underservice. PMID- 22315901 TI - A look at The Joint Commission: next stop, high reliability. PMID- 22315902 TI - Looking forward. Paul Collicott. PMID- 22315903 TI - Electronic prescribing in 2011. PMID- 22315904 TI - Telemedicine consultation for emergency trauma: the 130 million square foot trauma. PMID- 22315905 TI - Disclosing sleep: an ethical challenge from the eFAcs.org. Ethical issues in surgery community. PMID- 22315906 TI - Elias S. Hanna, MD, FACS, opens his heart to patients the world over. PMID- 22315907 TI - Extremes of age: surprising similarities of pediatric and geriatric surgery. PMID- 22315908 TI - Health care integration: will physicians lose their voice? PMID- 22315909 TI - Running for political office. PMID- 22315910 TI - A parent's death: helping a child after devastating trauma. PMID- 22315911 TI - How should extravasation injuries be treated? PMID- 22315912 TI - Nodules that developed months after treatment. PMID- 22315913 TI - A day in the life. PMID- 22315914 TI - Childhood obesity: understanding the causes, beginning the discussion. PMID- 22315915 TI - Immune thrombocytopenic purpura develops in a 67-year-old female. PMID- 22315916 TI - Interactions between supplements and drugs: deciphering the evidence. PMID- 22315917 TI - The physician assistant workforce in Indiana: preparing to meet future health care needs. AB - OBJECTIVE: This study identifies baseline demographic and descriptive statistics for physician assistants (PAs) in Indiana from 1978 to 2010. METHODS: Data were obtained from Indiana Professional Licensing Agency applications, the Indiana State Department of Health, and PA educational programs. Descriptive statistics were used to characterize the PA workforce as well as their supervising physicians. RESULTS: Most PAs working in Indiana were born and educated outside the state. Of those educated in Indiana, 77% obtained an initial license in Indiana; as of May 2010, 62% were still licensed in the state. In the past 8 years, Indiana had a 97% increase in active licensed PAs. Only 24% of PAs work in primary care; 92% work in metropolitan areas. For 40 years, PAs have increasingly worked in areas that are medically underserved or experiencing a shortage of health professionals. However, the overall numbers of PAs working in those areas remain low. CONCLUSIONS: More PAs in Indiana are practicing in medical specialties than in primary care. As health care policy and regulatory changes evolve, future studies will be needed to understand the impact on the health care workforce of Indiana PAs. This study will serve as a baseline for those studies. PMID- 22315918 TI - Childhood obesity: complications, prevention strategies, treatment. PMID- 22315919 TI - Lung cancer: screening, staging, targeted therapies. PMID- 22315920 TI - After the error, then what? The emotional impact of errors on clinicians. PMID- 22315921 TI - Atypical manifestations of a potentially fatal infection. PMID- 22315922 TI - An unlikely afternoon hero: when being there is good enough. PMID- 22315923 TI - Case of the month. Osteochondritis dissecans. PMID- 22315924 TI - The London low emission zone baseline study. AB - On February 4, 2008, the world's largest low emission zone (LEZ) was established. At 2644 km2, the zone encompasses most of Greater London. It restricts the entry of the oldest and most polluting diesel vehicles, including heavy-goods vehicles (haulage trucks), buses and coaches, larger vans, and minibuses. It does not apply to cars or motorcycles. The LEZ scheme will introduce increasingly stringent Euro emissions standards over time. The creation of this zone presented a unique opportunity to estimate the effects of a stepwise reduction in vehicle emissions on air quality and health. Before undertaking such an investigation, robust baseline data were gathered on air quality and the oxidative activity and metal content of particulate matter (PM) from air pollution monitors located in Greater London. In addition, methods were developed for using databases of electronic primary-care records in order to evaluate the zone's health effects. Our study began in 2007, using information about the planned restrictions in an agreed-upon LEZ scenario and year-on-year changes in the vehicle fleet in models to predict air pollution concentrations in London for the years 2005, 2008, and 2010. Based on this detailed emissions and air pollution modeling, the areas in London were then identified that were expected to show the greatest changes in air pollution concentrations and population exposures after the implementation of the LEZ. Using these predictions, the best placement of a pollution monitoring network was determined and the feasibility of evaluating the health effects using electronic primary-care records was assessed. To measure baseline pollutant concentrations before the implementation of the LEZ, a comprehensive monitoring network was established close to major roadways and intersections. Output difference plots from statistical modeling for 2010 indicated seven key areas likely to experience the greatest change in concentrations of nitrogen dioxide (NO2) (at least 3 microg/m3) and of PM with an aerodynamic diameter < or = 10 microm (PM10) (at least 0.75 microg/m3) as a result of the LEZ; these suggested that the clearest signals of change were most likely to be measured near roadsides. The seven key areas were also likely to be of importance in carrying out a study to assess the health outcomes of an air quality intervention like the LEZ. Of the seven key areas, two already had monitoring sites with a full complement of equipment, four had monitoring sites that required upgrades of existing equipment, and one required a completely new installation. With the upgrades and new installations in place, fully ratified (verified) pollutant data (for PM10, PM with an aerodynamic diameter < or = 2.5 microm [PM2.5], nitrogen oxides [NOx], and ozone [O3] at all sites as well as for particle number, black smoke [BS], carbon monoxide [CO], and sulfur dioxide [SO2] at selected sites) were then collected for analysis. In addition, the seven key monitoring sites were supported by other sites in the London Air Quality Network (LAQN). From these, a robust set of baseline air quality data was produced. Data from automatic and manual traffic counters as well as automatic license-plate recognition cameras were used to compile detailed vehicle profiles. This enabled us to establish more precise associations between ambient pollutant concentrations and vehicle emissions. An additional goal of the study was to collect baseline PM data in order to test the hypothesis that changes in traffic densities and vehicle mixes caused by the LEZ would affect the oxidative potential and metal content of ambient PM10 and PM2.5. The resulting baseline PM data set was the first to describe, in detail, the oxidative potential and metal content of the PM10 and PM2.5 of a major city's airshed. PM in London has considerable oxidative potential; clear differences in this measure were found from site to site, with evidence that the oxidative potential of both PM10 and PM2.5 at roadside monitoring sites was higher than at urban background locations. In the PM10 samples this increased oxidative activity appeared to be associated with increased concentrations of copper (Cu), barium (Ba), and bathophenanthroline disulfonate-mobilized iron (BPS Fe) in the roadside samples. In the PM2.5 samples, no simple association could be seen, suggesting that other unmeasured components were driving the increased oxidative potential in this fraction of the roadside samples. These data suggest that two components were contributing to the oxidative potential of roadside PM, namely Cu and BPS Fe in the coarse fraction of PM (PM with an aerodynamic diameter of 2.5 microm to 10 microm; PM(2.5-10)) and an unidentified redox catalyst in PM2.5. The data derived for this baseline study confirmed key observations from a more limited spatial mapping exercise published in our earlier HEI report on the introduction of the London's Congestion Charging Scheme (CCS) in 2003 (Kelly et al. 2011a,b). In addition, the data set in the current report provided robust baseline information on the oxidative potential and metal content of PM found in the London airshed in the period before implementation of the LEZ; the finding that a proportion of the oxidative potential appears in the PM coarse mode and is apparently related to brake wear raises important issues regarding the nature of traffic management schemes. The final goal of this baseline study was to establish the feasibility, in ethical and operational terms, of using the U.K.'s electronic primary-care records to evaluate the effects of the LEZ on human health outcomes. Data on consultations and prescriptions were compiled from a pilot group of general practices (13 distributed across London, with 100,000 patients; 29 situated in the inner London Borough of Lambeth, with 200,000 patients). Ethics approvals were obtained to link individual primary-care records to modeled NOx concentrations by means of post-codes. (To preserve anonymity, the postcodes were removed before delivery to the research team.) A wide range of NOx exposures was found across London as well as within and between the practices examined. Although we observed little association between NOx exposure and smoking status, a positive relationship was found between exposure and increased socioeconomic deprivation. The health outcomes we chose to study were asthma, chronic obstructive pulmonary disease, wheeze, hay fever, upper and lower respiratory tract infections, ischemic heart disease, heart failure, and atrial fibrillation. These outcomes were measured as prevalence or incidence. Their distributions by age, sex, socioeconomic deprivation, ethnicity, and smoking were found to accord with those reported in the epidemiology literature. No cross-sectional positive associations were found between exposure to NOx and any of the studied health outcomes; some associations were significantly negative. After the pilot study, a suitable primary-care database of London patients was identified, the General Practice Research Database responsible for giving us access to these data agreed to collaborate in the evaluation of the LEZ, and an acceptable method of ensuring privacy of the records was agreed upon. The database included about 350,000 patients who had remained at the same address over the four-year period of the study. Power calculations for a controlled longitudinal analysis were then performed, indicating that for outcomes such as consultations for respiratory illnesses or prescriptions for asthma there was sufficient power to identify a 5% to 10% reduction in consultations for patients most exposed to the intervention compared with patients presumed to not be exposed to it. In conclusion, the work undertaken in this study provides a good foundation for future LEZ evaluations. Our extensive monitoring network, measuring a comprehensive set of pollutants (and a range of particle metrics), will continue to provide a valuable tool both for assessing the impact of LEZ regulations on air quality in London and for furthering understanding of the link between PM's composition and toxicity. Finally, we believe that in combination with our modeling of the predicted population-based changes in pollution exposure in London, the use of primary-care databases forms a sound basis and has sufficient statistical power for the evaluation of the potential impact of the LEZ on human health. PMID- 22315925 TI - Total syntheses of (-)-hanishin, (-)-longamide B, and (-)-longamide B methyl ester via a novel preparation of N-substituted pyrrole-2-carboxylates [corrected]. AB - A novel preparation of N-substituted pyrrole-2-carboxylates has been developed based upon 1,3-dipolar cycloaddition and a conventional hydrogenolysis. By using this method as the key step, total syntheses of natural alkaloids (-)-hanishin, ( )-longamide [corrected] B, and (-)-longamide [corrected] B methyl ester were accomplished in the highest overall yields, respectively. PMID- 22315926 TI - Prosthesis use in adult acquired major upper-limb amputees: patterns of wear, prosthetic skills and the actual use of prostheses in activities of daily life. AB - PURPOSE: To describe patterns of prosthesis wear and perceived prosthetic usefulness in adult acquired upper-limb amputees (ULAs). To describe prosthetic skills in activities of daily life (ADL) and the actual use of prostheses in the performance of ADL tasks. To estimate the influence of prosthetic skills on actual prosthesis use and the influence of background factors on prosthetic skills and actual prosthesis use. METHOD: Cross-sectional study analysing population-based questionnaire data (n = 224) and data from interviews and clinical testing in a referred/convenience sample of prosthesis-wearing ULAs (n = 50). Effects were analysed using linear regression. RESULTS: 80.8% wore prostheses. 90.3% reported their most worn prosthesis as useful. Prosthetic usefulness profiles varied with prosthetic type. Despite demonstrating good prosthetic skills, the amputees reported actual prosthesis use in only about half of the ADL tasks performed in everyday life. In unilateral amputees, increased actual use was associated with sufficient prosthetic training and with the use of myoelectric vs cosmetic prostheses, regardless of amputation level. Prosthetic skills did not affect actual prosthesis use. No background factors showed significant effect on prosthetic skills. CONCLUSIONS: Most major ULAs wear prostheses. Individualised prosthetic training and fitting of myoelectric rather than passive prostheses may increase actual prosthesis use in ADL. PMID- 22315927 TI - Self-assembly of class II hydrophobins on polar surfaces. AB - Hydrophobins are structural proteins produced by filamentous fungi that are amphiphilic and function through self-assembling into structures such as membranes. They have diverse roles in the growth and development of fungi, for example in adhesion to substrates, for reducing surface tension to allow aerial growth, in forming protective coatings on spores and other structures. Hydrophobin membranes at the air-water interface and on hydrophobic solids are well studied, but understanding how hydrophobins can bind to a polar surface to make it more hydrophobic has remained unresolved. Here we have studied different class II hydrophobins for their ability to bind to polar surfaces that were immersed in buffer solution. We show here that the binding under some conditions results in a significant increase of water contact angle (WCA) on some surfaces. The highest contact angles were obtained on cationic surfaces where the hydrophobin HFBI has an average WCA of 62.6 degrees at pH 9.0, HFBII an average of 69.0 degrees at pH 8.0, and HFBIII had an average WCA of 61.9 degrees at pH 8.0. The binding of the hydrophobins to the positively charged surface was shown to depend on both pH and ionic strength. The results are significant for understanding the mechanism for formation of structures such as the surface of mycelia or fungal spore coatings as well as for possible technical applications. PMID- 22315928 TI - Lattice parameter accommodation between GaAs(111) nanowires and Si(111) substrate after growth via Au-assisted molecular beam epitaxy. AB - Using out-of-plane and in-plane X-ray diffraction techniques, we have investigated the structure at the interface between GaAs nanowires [NWs] grown by Au-assisted molecular beam epitaxy and the underlying Si(111) substrate. Comparing the diffraction pattern measured at samples grown for 5, 60, and 1,800 s, we find a plastic strain release of about 75% close to the NW-to-substrate interface even at the initial state of growth, probably caused by the formation of a dislocation network at the Si-to-GaAs interface. In detail, we deduce that during the initial stage, zinc-blende structure GaAs islands grow with a gradually increasing lattice parameter over a transition region of several 10 nm in the growth direction. In contrast, accommodation of the in-plane lattice parameter takes place within a thickness of about 10 nm. As a consequence, the ratio between out-of-plane and in-plane lattice parameters is smaller than the unity in the initial state of growth. Finally the wurtzite-type NWs grow on top of the islands and are free of strain. PMID- 22315929 TI - Asbestos in Canada: the end is in sight. PMID- 22315930 TI - Impacts on ambient air quality due to flaring activities in one of Oman's oilfields. AB - This work was conducted to assess the impacts on workplace and ambient air quality due to release of sulfur dioxide (SO(2)) into the atmosphere at Al-Noor production station, located in southern desert of Sultanate of Oman. The SO(2) is released because of oxidation of H(2)S to SO(2) on flaring of H(2)S rich off gas at the Al-Noor. In the first phase of the study, CALPUFF modeling system was used to predict the ground level concentrations of SO(2) emissions from the flare stacks. The evaluation of the modeling system was carried out by comparing the predicted results with that of the measured. In the second stage of the study, the estimated results were compared with the air quality standards/guidelines set by Omani regulatory authorities as well as by World Health Organization (WHO). It was concluded on the basis of current study that the sensitive individuals in the workplace of the Al-Noor could experience adverse health effects due to short term exposure of SO(2). PMID- 22315931 TI - Eczema increases susceptibility to PM10 in office indoor environments. AB - The objective was to compare impact of indoor office environment on employees with eczema with those without eczema. Exposure was measured at 56 sites and modelled for 173 work places. Tear film stability, lysozyme in nasal lavage, immunoglobulin E (IgE), and Phadiatop were assessed, and symptoms and perceptions collected by questionnaires. Multiple regression analyses were applied, adjusted for age, gender, strain, current smoking, and respiratory infections. Those with eczema perceived temperature too high but not associated with measured temperature. They had increased lysozyme in nasal lavage associated with increased air temperature difference between 6 and 10 AM, more general and mucosal symptoms, and "dry or flushed facial skin" associated with airborne particulate matter less than 10 microns in diameter (PM(10)). Impact of PM(10) was most pronounced among those with eczema previous 30 days. Having eczema might be an important predictor for subjective and objective responses to indoor environment. PMID- 22315932 TI - Effect of chronic pesticide exposure in farm workers of a Mexico community. AB - Pesticides are frequently used substances worldwide, even when the use of some of them is forbidden due to the recognized adverse effect they have on the health of not only the people who apply the pesticides, but also of those that consume the contaminated products. The objectives of this study were to know the health issues of farm workers chronically exposed to pesticides, to evaluate possible damage at genetic level, as well as to explore some hepatic, renal, and hematological alterations. A transversal comparative study was performed between 2 groups, one composed of 25 farm workers engaged in pesticide spraying, and a control group of 21 workers not exposed to pesticides; both groups belonged to the Nextipac community in Jalisco, Mexico. Each member of both groups underwent a full medical history. Blood samples were taken from all farm workers in order to obtain a complete blood count and chemistry, clinical chemistry, lipid profile, liver and kidney function tests, erythrocyte cholinesterase quantification, lipid peroxidation profile, and free DNA fragment quantification. For the information analysis, central tendency and dispersion measurements were registered. In order to know the differences between groups, a cluster multivariate method was used, as well as prevalence reasons. The most used pesticides were mainly organophosphates, triazines and organochlorine compounds. The exposed group showed acute poisoning (20% of the cases) and diverse alterations of the digestive, neurological, respiratory, circulatory, dermatological, renal, and reproductive system probably associated to pesticide exposure. More importantly, they presented free DNA fragments in plasma (90.8 vs 49.05 ng/mL) as well as a higher level of lipid peroxidation (41.85 vs. 31.91 nmol/mL) in comparison with those data from unexposed farm workers. These results suggest that there exist health hazards for those farm workers exposed to pesticides, at organic and cellular levels. PMID- 22315933 TI - Exposure to electromagnetic fields from laptop use of "laptop" computers. AB - Portable computers are often used at tight contact with the body and therefore are called "laptop." The authors measured electromagnetic fields (EMFs) laptop computers produce and estimated the induced currents in the body, to assess the safety of laptop computers. The authors evaluated 5 commonly used laptop of different brands. They measured EMF exposure produced and, using validated computerized models, the authors exploited the data of one of the laptop computers (LTCs) to estimate the magnetic flux exposure of the user and of the fetus in the womb, when the laptop is used at close contact with the woman's womb. In the LTCs analyzed, EMF values (range 1.8-6 MUT) are within International Commission on Non-Ionizing Radiation (NIR) Protection (ICNIRP) guidelines, but are considerably higher than the values recommended by 2 recent guidelines for computer monitors magnetic field emissions, MPR II (Swedish Board for Technical Accreditation) and TCO (Swedish Confederation of Professional Employees), and those considered risky for tumor development. When close to the body, the laptop induces currents that are within 34.2% to 49.8% ICNIRP recommendations, but not negligible, to the adult's body and to the fetus (in pregnant women). On the contrary, the power supply induces strong intracorporal electric current densities in the fetus and in the adult subject, which are respectively 182-263% and 71-483% higher than ICNIRP 98 basic restriction recommended to prevent adverse health effects. Laptop is paradoxically an improper site for the use of a LTC, which consequently should be renamed to not induce customers towards an improper use. PMID- 22315934 TI - Prevalence of musculoskeletal disorders among cashew factory workers. AB - Work-related musculoskeletal disorders (WRMSDs) are impairments of the bodily structures, such as muscles, joints, tendons, ligaments, nerves, or the localized blood circulation system, which are caused or aggravated primarily by the performance of work and by the effects of the immediate environment in which work is carried out. Types of work in the cashew factory include cutting, peeling, grading, packing, and boiling. All these activities have risk factors for the musculoskeletal disorders, which include repetition, contact stress, forceful contraction, awkward postures, as well as sustained positions. The objective of this cross-sectional study was to find out the prevalence of musculoskeletal disorders among cashew factory workers. A cross-sectional descriptive study was conducted on 246 cashew factory workers, working in a randomly selected factory of a selected locality in Karkala taluk of Udupi district, Karnataka. Participants' name, age, gender, literacy level, income, type of work, duration of employment, hours of work per day, hand dominance, pain and discomfort status were obtained by structured interview. A total of 246 cashew factory workers participated in the study. Data were analyzed using SPSS version 14. Descriptive statistics was used to summarize the data. Around 28.5% (n = 70) reported pain, whereas 71.5% (n = 176) of workers did not report pain. The largest number of workers (n = 22; 32.4%) complained of pain in the knee, followed by back (n = 21; 30.9%) and then shoulder (n = 8; 11.8%). Seventy percent of the workers who reported pain were having more than 5 years of work experience. A 68.6% (n = 48) of the workers who reported pain were in the cutting category, followed by the grading (17%; n = 12), boiling (8.6%; n = 6), and peeling (5.7%; n = 4) categories. Prevalence of pain and discomfort among workers was 28.5%, which is a not ignorable and has to be addressed. Self-reported pain and discomfort were more prevalent in knee, followed by back and then shoulder. PMID- 22315935 TI - Pesticide-induced scleroderma and early intensive immunosuppressive treatment. AB - The authors report 2 children with generalized cutaneous sclerosis exposed to pesticides containing malathion and diniconazole. Treatment with immunosuppressives resulted in partial improvement in the cutaneous signs, particularly over the face, trunk, and proximal limbs. The considerable exposure to chemicals related with the initiation of symptoms and absence of organ involvement suggested a diagnosis of chemically induced scleroderma-like disorder. Although autoantibodies were negative, previously reported relevant associations of anti-kinetochore and anti-topoisomerase function of active ingredients-diniconazole and phosphorodithioate-and solvents of these pesticides are also discussed. Careful follow-up for systemic involvement is warranted, since these agents may have triggered systemic scleroderma in these patients. Elimination of chemical exposure of children is stressed. PMID- 22315936 TI - Corneal metallic foreign body injuries due to suboptimal ocular protection. AB - Retrospective review of 100 consecutive presentations of metallic corneal foreign body to the Royal Victorian Eye and Ear Hospital emergency department was undertaken between November and December 2009. The majority of the patients (97%) were male with a mean age of 42 +/- 13 years (range 19-73 years). The most common mode of injury was grinding (88%). Nearly half (45%) of patients were wearing "safety eye wear" at the time of injury. Combination of 25-gauge needle and burr was the commonest method employed for removal of foreign body. Overall, 88% (n = 88) cases healed with corneal scar at the site of corneal foreign body and 1 case developed bacterial keratitis. Metallic corneal foreign bodies are common presentations to the emergency department and may be related to inadequate implementation of occupational safety measures. PMID- 22315937 TI - Comment on: "Visual contrast sensitivity in children exposed to tetrachloroethylene" by Storm et al. PMID- 22315939 TI - Into a new era: volume 1 of the Archives of Environmental Health, July 1960. PMID- 22315942 TI - Hope for recovery - how clinicians may facilitate this in their work. AB - BACKGROUND: The importance of having hope for recovery has been highlighted in numerous qualitative studies of recovery. It is identified as a vital part of this process, and guidelines suggest that service providers should therefore facilitate hope in their clinical work; however, they do not indicate how this guidance can be operationalised. AIMS: To identify the sources of hope for recovery based on the accounts of people with experience of recovery; to ascertain how these accounts show service providers can facilitate such hope in their therapeutic work. METHOD: Semi-structured interviews were conducted with eight people with experience of recovering from mental health problems. A grounded theory analysis was undertaken. RESULTS: A model conceptualising the role of hope in recovery was developed with three categories: "influence of others on hope", "personal hope" and "doing recovery". The model indicates a complex interaction between hope and recovery with an important role for social context and interpersonal relationships, including those with clinicians. CONCLUSIONS: Mental health service providers occupy a powerful position in relation to service users' hope, and must carefully consider how they communicate their own hopefulness about clients' recovery. Suggestions are made about facilitating hope for recovery. PMID- 22315944 TI - Psychosocial outcomes in children with and without non-syndromic craniosynostosis: findings from two studies. AB - Objective : To evaluate the hypothesis that children with craniosynostosis and their parents have differences in psychosocial outcomes, as compared with an unaffected control group. Design : Two studies were conducted, both which followed children born with and without craniosynostosis. Study 1 ascertained affected children from clinics, and study 2 ascertained affected children from a population-based study of birth defects. Participants : Study 1 included 22 children with single-suture craniosynostosis and 18 controls, ages 4 to 5 years. Study 2 included 24 children with nonsyndromic craniosynostosis and 124 unaffected controls, ages 5 to 9 years. Main Outcome Measures : Outcome measures included the Child Behavior Checklist, Social Competence Scale, Pediatric Quality of Life Inventory, and Parenting Stress Index. Results : We observed lower scores on measures of health-related quality of life in cases versus controls, with adjusted effect sizes ranging from -0.72 to -0.44 (p < .05) on summary measures. Small but statistically nonsignificant increases in behavioral problems were observed in cases versus controls, with no apparent differences in social competence or parenting stress. Conclusions : Results provide preliminary evidence suggesting that children with nonsyndromic craniosynostosis may have elevated risk for psychosocial difficulties, particularly health-related quality of life. Continued follow-up through preadolescence and adolescence is warranted. PMID- 22315946 TI - Interaction of 2'-deoxyadenosine with cis-2-butene-1,4-dial: computational approach to analysis of multistep chemical reactions. AB - The computational analysis of multistep chemical interactions between 2' deoxyadenosine and cis-2-butene-1,4-dial has been performed. The applied protocol includes generation of a multistep Gibbs free-energy reaction profile (PCM/M05 2X/6-311+G(d) level) for the transformations of the reagents to products, followed by evaluation of the rate constants, construction of the corresponding kinetic equations, and solving them. Such a procedure allows one to significantly extend the number of experimentally determined steps by addition of the ones computationally predicted. The primary products of the reaction are found to be four diastereomeric adducts characterized by virtually the same stability. The acid-catalyzed dehydration of these adducts leads to a more stable secondary product. Computational verification of UV and NMR spectra has also been performed. It has been revealed that simulated UV and NMR spectra of primary and secondary 2'-deoxyadenosine adducts of cis-2-butene-1,4-dial are in agreement with the experimental observations. PMID- 22315945 TI - Interleukin-10 produced by B cells is crucial for the suppression of Th17/Th1 responses, induction of T regulatory type 1 cells and reduction of collagen induced arthritis. AB - INTRODUCTION: Interleukin-10 (IL-10) producing B cells, also known as regulatory B (Breg) cells, play a key role in controlling autoimmunity. Our laboratory and others have demonstrated a pivotal role for Bregs in rheumatological disorders, including experimental models of arthritis and lupus. The aim of this study was to identify the role of endogenous IL-10 secreting B cells in vivo in controlling the induction and disease progression of collagen-induced arthritis (CIA). METHODS: We generated chimeric mice that had IL-10 knocked-out specifically in the B cell population. These mice were compared with wild-type (WT) B cell chimeric mice for their susceptibility to CIA. RESULTS: Here we report that chimeric mice specifically lacking IL-10 producing B cells (IL-10-/- B cell) developed an exacerbated CIA compared to chimeric wild type B cell (WT B cell) mice. A marked increase in inflammatory Th1 and Th17 cells were detected in IL-10 /-B cell mice compared to WT B cell mice. Furthermore, there was a reduction in IL-10 secreting CD4+ Tr1 cells in these animals. CONCLUSIONS: IL-10 producing B cells restrain inflammation by promoting differentiation of immuno-regulatory over pro-inflammatory T cells and, hence, act to maintain tolerance. PMID- 22315947 TI - Can physical therapists counsel patients with lifestyle-related health conditions effectively? A systematic review and implications. AB - OBJECTIVE: Healthcare professionals' competence in health behavior change has lagged behind other clinical competencies despite the well-established relationship between lifestyle behavior and health. We conducted a systematic review to examine whether physical therapists, given their unique practice pattern, can counsel effectively. METHODS: Databases including MEDLINE, EMBASE, CINAHL, PsycINFO, and the Cochrane Database of Systematic Reviews were assessed from 1950 to July 2010. Studies were limited to the English, German, and Dutch languages. The methodological quality was evaluated (Downs and Black tool). RESULTS: Seven source articles with a mean quality score of 16.57 +/- 4.24 points (range: low = 0; high = 28) were retrieved. Given considerable methodological heterogeneity, the studies were compared in a narrative synthesis. The target populations, types and periods of interventions, outcome measures, and findings were analyzed. CONCLUSION: Physical therapists can effectively counsel patients with respect to lifestyle behavior change, at least in the short term. They can be effective health counselors individually or within an interprofessional team. PRACTICE IMPLICATIONS: Multiple health behavior change needs to be a primary twenty-first century clinical competence in physical therapy. Future studies will establish the degree to which effective health counseling augments physical therapy as well as health outcomes, in the long as well as short term. PMID- 22315948 TI - Aspirin for the prevention of cognitive decline in the elderly: rationale and design of a neuro-vascular imaging study (ENVIS-ion). AB - BACKGROUND: This paper describes the rationale and design of the ENVIS-ion Study, which aims to determine whether low-dose aspirin reduces the development of white matter hyper-intense (WMH) lesions and silent brain infarction (SBI). Additional aims include determining whether a) changes in retinal vascular imaging (RVI) parameters parallel changes in brain magnetic resonance imaging (MRI); b) changes in RVI parameters are observed with aspirin therapy; c) baseline cognitive function correlates with MRI and RVI parameters; d) changes in cognitive function correlate with changes in brain MRI and RVI and e) whether factors such as age, gender or blood pressure influence the above associations. METHODS/DESIGN: Double blind, placebo-controlled trial of three years duration set in two Australian academic medical centre outpatient clinics. This study will enrol 600 adults aged 70 years and over with normal cognitive function and without overt cardiovascular disease. Subjects will undergo cognitive testing, brain MRI and RVI at baseline and after 3 years of study treatment. All subjects will be recruited from a 19,000-patient clinical outcome trial conducted in Australia and the United States that will evaluate the effects of aspirin in maintaining disability-free longevity over 5 years. The intervention will be aspirin 100 mg daily versus matching placebo, randomized on a 1:1 basis. DISCUSSION: This study will improve understanding of the mechanisms at the level of brain and vascular structure that underlie the effects of aspirin on cognitive function. Given the limited access and high cost of MRI, RVI may prove useful as a tool for the identification of individuals at high risk for the development of cerebrovascular disease and cognitive decline. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01038583. PMID- 22315949 TI - Association between infant formula feeding and dental fluorosis and caries in Australian children. AB - OBJECTIVE: The objective of this study was to evaluate associations between patterns of infant formula feeding and dental fluorosis and caries in a representative sample of Australian children. METHODS: A population-based study gathered information on fluoride exposure in early childhood. Information on infant formula feeding and fluoridation status was used to group children: three groups in nonfluoridated areas (formula nonuser, user for <=6 months, and user for 6+ months) and four groups in fluoridated areas (nonuser, user with nonfluoridated water, user with fluoridated water for <=6 months, and user with fluoridated water for 6+ months). Children aged 8-13 years were examined for fluorosis using the Thylstrup and Fejerskov (TF) Index. Primary tooth caries experience recorded at age 8-9 years was extracted from clinical records. Fluorosis cases were defined as having TF 1+ on maxillary incisors. Fluorosis prevalence and primary caries experience were compared across formula user groups in multivariable regression models adjusting for other factors. RESULTS: Total sample was 588 children. Children in fluoridated areas had higher prevalence of very mild to mild fluorosis, but lower caries experience than those in nonfluoridated areas. Among children in nonfluoridated areas, formula users for 6+ months had significantly higher prevalence of fluorosis compared with nonusers. There was no significant difference in fluorosis prevalence among the formula users in fluoridated areas. Among children in fluoridated areas, formula users with nontap water had higher caries experience. CONCLUSION: Infant formula use was associated with higher prevalence of fluorosis in nonfluoridated areas but not in fluoridated areas. Type of water used for reconstituting infant formula in fluoridated areas was associated with caries experience. PMID- 22315950 TI - Evaluation of heterogeneity dose distributions for Stereotactic Radiotherapy (SRT): comparison of commercially available Monte Carlo dose calculation with other algorithms. AB - BACKGROUND: The purpose of this study was to compare dose distributions from three different algorithms with the x-ray Voxel Monte Carlo (XVMC) calculations, in actual computed tomography (CT) scans for use in stereotactic radiotherapy (SRT) of small lung cancers. METHODS: Slow CT scan of 20 patients was performed and the internal target volume (ITV) was delineated on Pinnacle3. All plans were first calculated with a scatter homogeneous mode (SHM) which is compatible with Clarkson algorithm using Pinnacle3 treatment planning system (TPS). The planned dose was 48 Gy in 4 fractions. In a second step, the CT images, structures and beam data were exported to other treatment planning systems (TPSs). Collapsed cone convolution (CCC) from Pinnacle3, superposition (SP) from XiO, and XVMC from Monaco were used for recalculating. The dose distributions and the Dose Volume Histograms (DVHs) were compared with each other. RESULTS: The phantom test revealed that all algorithms could reproduce the measured data within 1% except for the SHM with inhomogeneous phantom. For the patient study, the SHM greatly overestimated the isocenter (IC) doses and the minimal dose received by 95% of the PTV (PTV95) compared to XVMC. The differences in mean doses were 2.96 Gy (6.17%) for IC and 5.02 Gy (11.18%) for PTV95. The DVH's and dose distributions with CCC and SP were in agreement with those obtained by XVMC. The average differences in IC doses between CCC and XVMC, and SP and XVMC were -1.14% (p = 0.17), and -2.67% (p = 0.0036), respectively. CONCLUSIONS: Our work clearly confirms that the actual practice of relying solely on a Clarkson algorithm may be inappropriate for SRT planning. Meanwhile, CCC and SP were close to XVMC simulations and actual dose distributions obtained in lung SRT. PMID- 22315951 TI - Functional dysbiosis within the gut microbiota of patients with constipated irritable bowel syndrome. AB - BACKGROUND: The role of the gut microbiota in patho-physiology of irritable bowel syndrome (IBS) is suggested by several studies. However, standard cultural and molecular methods used to date have not revealed specific and consistent IBS related groups of microbes. AIM: To explore the constipated-IBS (C-IBS) gut microbiota using a function-based approach. METHODS: The faecal microbiota from 14 C-IBS women and 12 sex-match healthy subjects were examined through a combined strictly anaerobic cultural evaluation of functional groups of microbes and fluorescent in situ hybridisation (16S rDNA gene targeting probes) to quantify main groups of bacteria. Starch fermentation by C-IBS and healthy faecal samples was evaluated in vitro. RESULTS: In C-IBS, the numbers of lactate-producing and lactate-utilising bacteria and the number of H(2) -consuming populations, methanogens and reductive acetogens, were at least 10-fold lower (P < 0.05) compared with control subjects. Concomitantly, the number of lactate- and H(2) utilising sulphate-reducing population was 10 to 100 fold increased in C-IBS compared with healthy subjects. The butyrate-producing Roseburia - E. rectale group was in lower number (0.01 < P < 0.05) in C-IBS than in control. C-IBS faecal microbiota produced more sulphides and H(2) and less butyrate from starch fermentation than healthy ones. CONCLUSIONS: A major functional dysbiosis was observed in constipated-irritable bowel syndrome gut microbiota, reflecting altered intestinal fermentation. Sulphate-reducing population increased in the gut of C-IBS and were accompanied by alterations in other microbial groups. This could be responsible for changes in the metabolic output and enhancement in toxic sulphide production which could in turn influence gut physiology and contribute to IBS pathogenesis. PMID- 22315952 TI - Rapid detection of foodborne botulism outbreaks facilitated by epidemiological linking of cases: implications for food defense and public health response. AB - The main objective of this study was to develop an understanding of the descriptive epidemiology of foodborne botulism in the context of outbreak detection and food defense. This study used 1993-2008 data from the Centers for Disease Control and Prevention (CDC) Annual Summaries of Notifiable Diseases, 2003-2006 data from the Bacterial Foodborne and Diarrheal Disease National Case Surveillance Annual Reports, and 1993-2008 data from the Annual Listing of Foodborne Disease Outbreaks. Published outbreak investigation reports were identified through a PubMed search of MEDLINE citations for botulism outbreaks. Fifty-eight foodborne botulism outbreaks were reported to CDC between 1993 and 2008. Four hundred sixteen foodborne botulism cases were documented; 205 (49%) were associated with outbreaks. Familial connections and co-hospitalization of initial presenting cases were common in large outbreaks (>5 cases). In these outbreaks, the time from earliest exposure to outbreak recognition varied dramatically (range, 48-216 h). The identification of epidemiologic linkages between foodborne botulism cases is a critical part of diagnostic evaluation and outbreak detection. Investigation of an intentionally contaminated food item with a long shelf life and widespread distribution may be delayed until an astute physician suspects foodborne botulism; suspicion of foodborne botulism occurs more frequently when more than one case is hospitalized concurrently. In an effort to augment national botulism surveillance and antitoxin release systems and to improve food defense and public health preparedness efforts, medical organizations and Homeland Security officials should emphasize the education and training of medical personnel to improve foodborne botulism diagnostic capabilities to recognize single foodborne botulism cases and to look for epidemiologic linkages between suspected cases. PMID- 22315953 TI - Acute allergic reactions in Vietnamese children after drinking a new milk product. AB - In early October 2009, pediatricians in hospitals in Ho Chi Minh City (HCMC) reported an unusual increase in the number of children presenting with an acute onset of itchy rash and some with breathing difficulties shortly after drinking milk products. The pediatricians considered the illness to be an allergic reaction to milk. The objective of our investigation was to identify the cause of this acute illness. Following early case reports, all hospitals in HCMC were requested to report cases of this illness. Parents were advised to take children with symptoms to a hospital immediately. A case-series was conducted to generate hypotheses on the possible causes of the illness and was followed by a case control study to test the hypothesis. Parents of all cases and controls were interviewed face-to-face. The association between food items and the allergy was tested using conditional logistics regression. From 9 to 28 October 2009, 19 cases fulfilled the case definition, and 16 of the 17 cases included in the study had consumed milk supplemented with galacto-oligosaccharides (GOS) shortly before the onset of illness. Fifty age-matched, neighborhood controls were enrolled into the case control study. Of the 30 food items consumed by study participants in the preceding 24 h, only the odds ratio (OR) of milk supplemented with GOS was statistically significant: OR=34.0 (95% CI=3.9, 294.8). Laboratory tests of this milk product did not reveal any unusual properties, chemicals, or other toxic substances. This is the first report of an acute allergic reaction to fresh milk supplemented with GOS. However, the specific allergen in this product was not identified. Further cases were not reported once this product was withdrawn from sale. Vietnam's food safety authorities should expand laboratory capacity to detect allergens in food products. PMID- 22315954 TI - Role of curli and cellulose expression in adherence of Escherichia coli O157:H7 to spinach leaves. AB - Shiga-toxigenic Escherichia coli O157:H7 outbreaks have been linked to consumption of fresh produce. It is generally recognized that bacterial attachment to vegetal matrices constitutes the first step in contamination of fresh produce. Cellular appendages, such as curli fibers, and cellulose, a constituent of extracellular matrix, have been suggested to be involved in E. coli attachment and persistence in fresh produce. A comparative evaluation was conducted on the ability of Shiga toxin-producing E. coli O157:H7 strains EDL933 and 86-24, linked to two independent foodborne disease outbreaks in humans, and their mutants deficient in curli and/or cellulose expression to colonize and to firmly attach to spinach leaf. Inoculated spinach leaves were incubated at 22 degrees C, and at 0, 24, and 48 h after incubation loosely and strongly attached E. coli O157:H7 populations were determined. Curli-expressing E. coli O157:H7 strains developed stronger association with leaf surface, whereas curli-deficient mutants attached to spinach at significantly (p<0.01) lower numbers. Attachment of cellulose-impaired mutants to spinach leaves was not significantly different from that of curliated strains. The relative attachment strength of E. coli O157:H7 to spinach increased with incubation time for the curli-expressing strains. Laser scanning confocal microscopy (LSCM) analysis of inoculated leaves revealed that curli-expressing E. coli O157:H7 were surrounded by extracellular structures strongly immunostained with anti-curli antibodies. Production of cellulose was not required to develop strong attachment to spinach leaf. These results indicate that curli fibers are essential for strong attachment of E. coli O157:H7 to spinach whereas cellulose is dispensable. PMID- 22315955 TI - Genomic presence of gadD1 glutamate decarboxylase correlates with the organization of ascB-dapE internalin cluster in Listeria monocytogenes. AB - The ability to survive and proliferate in acidic environments is a prerequisite for the infection of Listeria monocytogenes. The glutamate decarboxylase (GAD) system is responsible for acid resistance, and three GAD homologs have been identified in L. monocytogenes: gadD1, gadD2, and gadD3. To examine whether GAD genes are specific to lineage, serovar, or certain subpopulation, we performed a systematic investigation on the prevalence of GAD genes in 164 L. monocytogenes. In contrast to gadD2 and gadD3 conserved in all L. monocytogenes strains, gadD1 was identified in 36.6% (60/164) of L. monocytogenes strains, including all serovar 1/2c and 68.5% (37/54) of serovar 1/2a strains, as well as a small fraction of serovar 1/2b (3.4%, 1/29) and lineage III (13.8%, 4/29) strains. All serovar 4b and lineage IV strains lacked this gene. According to the ascB-dapE structure, L. monocytogenes strains were classified into four subpopulations, carrying inlC2DE, inlGC2DE, inlGHE, or no internalin cluster, respectively. All L. monocytogenes strains with inlGC2DE or inlGHE pattern harbored gadD1, whereas those bearing inlC2DE or no internalin cluster between ascB and dapE lacked gadD1. In addition, other five non-monocytogenes Listeria species lacking ascB dapE internalin cluster were gadD1-negative. Overall, the presence of gadD1 is not fully dependent on lineages or serovars but correlates with ascB-dapE internalin profiles, suggesting gadD1 might have co-evolved with the ascB-dapE internalin cluster in the primitive L. monocytogenes before divergence of serovars. PMID- 22315956 TI - Proteomic profiling of acute coronary thrombosis reveals a local decrease in pigment epithelium-derived factor in acute myocardial infarction. AB - Thrombotic occlusion of an epicardial coronary artery on the grounds of atherosclerotic plaque is considered the ultimate step in AMI (acute myocardial infarction). However, the precise pathophysiological mechanisms underlying acute coronary occlusion are not fully understood. We have analysed proteomic profiles of systemic plasma and plasma derived from the site of coronary plaque rupture of non-diabetic patients with STEMI (ST-segment elevation myocardial infarction). Label-free quantification of MS/MS (tandem MS) data revealed differential regulation of complement cascade components and a decrease in anti-thrombotic PEDF (pigment epithelium-derived factor) between CS (culprit site)-derived plasma and systemic plasma. PEDF, which is known to have a protective role in atherothrombosis, was relatively decreased at the CS, with a level of expression inverse to local MMP-9 (matrix metalloproteinase-9) activity. CS plasma displayed enhanced proteolytic activity towards PEDF. Proteomics of coronary thrombus aspirates indicate that PEDF processing is associated with coronary plaque rupture. PMID- 22315957 TI - A new frailty syndrome: central obesity and frailty in older adults with the human immunodeficiency virus. AB - OBJECTIVES: To evaluate the relationships between body composition and physical frailty in community-dwelling older adults with the human immunodeficiency virus (HIV) (HOA). DESIGN: Cross-sectional. SETTING: Academic hospital-based infectious disease clinic in Rochester, New York. PARTICIPANTS: Forty community-dwelling HOA aged 50 and older undergoing antiretroviral therapy who were able to ambulate without assistive devices with a mean age of 58, a mean BMI of 29.0 kg/m(2), mean CD4 count of 569 cells/mL, and a mean duration since HIV diagnosis of 17 years; 28% were female and 57% Caucasian. MEASUREMENTS: Subjective and objective measures of functional status were evaluated using the Physical Performance Test (PPT), the graded treadmill test, knee strength, gait speed, balance, and the Functional Status Questionnaire (FSQ). Body composition was evaluated using dual energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI). RESULTS: Sixty percent (25/40) of the participants met standard criteria for physical frailty. Frail (FR) and nonfrail (NF) participants were comparable in age, sex, CD4 count, and viral load. FR HOA had greater impairments in PPT, peak oxygen uptake, FSQ, walking speed, balance, and muscle quality than NF HOA. FR HOA had a greater body mass index (BMI), fat mass, and truncal fat with lipodystrophy. Moreover, PPT score was inversely related to trunk fat (correlation coefficient (r) = -0.34; P = .04) and ratio of intermuscular fat to total fat (r = -0.60; P = .02) after adjusting for covariates. CONCLUSION: HOA represent an emerging cohort of older adults who frequently experience frailty at a much younger age than the general older population. Central obesity and fat redistribution are important predictors of frailty in community-dwelling HOA. These findings suggest that physical frailty in HOA may be amenable to lifestyle interventions, especially exercise and diet therapy. PMID- 22315958 TI - The role and function of cadherins in the mammary gland. AB - Cadherins are transmembrane receptors that function through calcium-dependent homophilic and heterophilic interactions that provide cell-cell contact and communication in many different organ systems. In the mammary gland only a few of the cadherins that make up this large superfamily of proteins have been characterized. Frequently in metastatic breast cancer, the genes for cadherins are epigenetically silenced, mutated, or regulated differently. During epithelial mesenchymal transition, cadherins that are expressed normally in the epithelial cells are down-regulated, while cadherins expressed in the mesenchyme are up regulated. This process is known as cadherin switching, and its regulation can sometimes facilitate the increased motility, invasiveness and proliferation that occurs in metastatic cancer cells. Depending on the context, however, cell motility, invasiveness, proliferation and expression of mesenchymal markers can be independently modulated from cadherin expression, leading to partial epithelial-mesenchymal transitions and even mesenchymal-epithelial transitions (METs). This review will summarize the current understanding of cadherins found in the mammary gland and what is known about their mechanism of regulation in the mammary gland during normal physiological conditions and in breast cancer. PMID- 22315960 TI - Psychological and social factors in undergoing reconstructive surgery among individuals with craniofacial conditions: an exploratory study. AB - Objective : Reconstructive surgery to improve psychological well-being is commonly offered to children with craniofacial conditions. Few studies have explored the challenges of reconstructive surgery beyond the physical risks: poor treatment outcomes, infection, brain damage, and death. This qualitative study aims to understand the psychological and social implications such interventions can have for individuals with craniofacial conditions. Design : A total of 38 individuals between the ages of 12 and 61 with such craniofacial conditions as Sturge-Weber syndrome, Treacher Collins syndrome, Mobius syndrome, cleft lip and palate, Noonan syndrome, Crouzon syndrome, and amniotic band syndrome participated in semistructured video-recorded interviews. Participants were recruited at conferences, through study flyers, and by word of mouth. Descriptive, thematic analysis was used to identify themes related to reconstructive surgery. Results : Dominant themes included undergoing surgery to reduce stigmatization, the psychological and social implications of the interventions, outcome satisfaction, parental involvement in decision making about surgery, and recommendations for parents considering surgery for their children with craniofacial conditions. Experiences with reconstructive surgery varied, with some participants expressing surgical benefits and others, disillusionment. Conclusions : The range of participant attitudes and experiences reflect the complexity of reconstructive surgery. Pediatric health care teams involved in the care of children with craniofacial conditions play an important role in advising patients (and their parents) about existing treatment options. The psychological and social implications of reconstructive surgery should be relayed to help families weigh the risks and benefits of surgery in an informed and meaningful way. PMID- 22315961 TI - Personalised computerised feedback in E-mental health. AB - BACKGROUND: Personalised feedback constitutes an important component of E- and M mental health applications (E = electronic and M = mobile computing and communication technologies) for disease prevention and management. It can be used to increase motivation, highlight risks, change attitudes and counterbalance the lack of personal contact in computerised health interventions. Research suggests that compared with targeted or generic feedback, personalised feedback is a more effective intervention component. AIMS: To discuss challenges and options for the generation and delivery of personalised feedback in E- and M-mental health interventions. Suggestions for the development of normative, summative and ipsative feedback are provided. RESULTS: We demonstrate how information from (multiple) assessments and/or data from comparable samples can be integrated into statistically supported and user-friendly feedback without including test scores. CONCLUSION: Proposals made in this paper need to be the subject of empirical studies and should be tested in terms of their feasibility, acceptability and efficacy. PMID- 22315962 TI - Kinematic differences between front crawl sprint and distance swimmers at a distance pace. AB - The purpose of the study was to determine whether there are differences in kinematics between sprint and distance front crawl specialists when swimming at a distance pace using a six beat kick. Seven sprint and eight distance male specialists performed one maximum 400 m swim through a 6.75 m3 calibrated space recorded by six gen-locked cameras. The following variables were calculated: average swim velocity, stroke length, stroke frequency, upper limb and foot displacement, elbow angle, the shoulder and hip roll angle, duration of the stroke phases and time corresponding to particular events within the stroke cycle relative to hand entry. Differences between the groups were assessed by an independent t-test and effect size (d) calculations for each variable. The groups only differed significantly with respect to the average swim velocity, with the distance swimmers maintaining a greater velocity throughout the 400 m. However, effect sizes were moderate for elbow angle range during the pull phase (d = 0.78) and the total hip roll magnitude (d = 0.76). There was little evidence to suggest that sprint and distance swimmers using a six beat kick pattern differ in technique when swimming at a distance pace and therefore coaches should not encourage the development of different techniques between these groups. PMID- 22315963 TI - Synthesis and characterization of novel 2-amino-3-benzoylthiophene derivatives as biased allosteric agonists and modulators of the adenosine A(1) receptor. AB - A series of novel 2-amino-3-benzoylthiophenes (2A3BTs) were screened using a functional assay of A(1)R mediated phosphorylation of extracellular signal regulated kinases 1 and 2 (ERK1/2) in intact CHO cells to identify potential agonistic effects as well as the ability to allosterically modulate the activity of the orthosteric agonist, R-PIA. Two derivatives, 8h and 8i, differing only in terms of the absence or presence of an electron-withdrawing group on the benzoyl moiety of the 2A3BT scaffold, were identified as biased allosteric agonists and positive allosteric modulators of agonist function at the adenosine A(1) receptor (A(1)R) in two different functional assays. Our findings indicate that subtle structural variations can promote functionally distinct receptor conformational states. PMID- 22315964 TI - Experimental and theoretical study of the reactions between vanadium oxide cluster cations and water. AB - Vanadium oxide cluster cations V(x)O(y)(+) (x = 2-6) are prepared by laser ablation and are reacted with D(2)O in a fast flow reactor under room temperature conditions. A time-of-flight mass spectrometer is used to detect the cluster distribution before and after the reactions. Observation of the products (V(2)O(5))(1-3)D(+) indicates the deuterium atom abstraction reaction (V(2)O(5))(1-3)(+) + D(2)O -> (V(2)O(5))(1-3)D(+) + OD. In addition, significant association products (V(2)O(5))(1-3)D(2)O(+) are also observed in the experiments. Density functional theory calculations are performed to study the reaction mechanisms of V(4)O(10)(+) with H(2)O. The calculated results are in agreement with the experimental observations and indicate that H(2)O is dissociatively rather than molecularly adsorbed in V(4)O(10)H(2)O(+) complex. PMID- 22315965 TI - Practical syntheses of proposed and revised manzacidin B and their congeners. AB - A concise and highly stereoselective total synthesis of manzacidin B and its congeners has been developed following chelation-controlled syn-epoxidation and Lewis acid catalyzed intramolecular regioselective epoxide ring opening to generate the quarternary amine center. Elaboration of the triol moiety to the target molecule was achieved in good overall yield, representing practical total syntheses of manzacidin B and its congeners. From the XRD, NMR, and analytical data, the correct structure of natural manzacidin B, (4R,5R,6R)-6, was confirmed. PMID- 22315967 TI - Potentially antigenic RBC membrane proteins in dogs with primary immune-mediated hemolytic anemia. AB - BACKGROUND: Primary immune-mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. The mechanisms underlying autoimmune reactivity remain poorly understood. OBJECTIVE: The aim of this study was to identify membrane proteins of RBCs that could be antigenic in dogs with primary IMHA. METHODS: Antibodies were eluted with xylene from RBCs of 12 dogs with IMHA, 4 dogs with anemia due to causes other than IMHA, and 2 healthy dogs. Pooled RBC membrane proteins were prepared from blood of 17 healthy dogs. The eluted antibodies were then analyzed by immunoblotting for interactions with the pooled membrane proteins and autologous plasma. Bands present in the 12 dogs with IMHA but not in the 6 other dogs were considered potential autoantigens and were identified by liquid chromatography followed by tandem mass spectrometry. RESULTS: RBC eluates from all 18 dogs had reactivity against band 3 protein. Antibodies to 6 additional proteins were uniquely identified in dogs with IMHA. Reactivity to calpain, complement component 3, and peroxiredoxin 2 was identified in 8, 8, and 4 of the 12 samples, respectively, from dogs with IMHA, but in none of the samples from the 6 dogs without IMHA. CONCLUSIONS: Detection of universal immune reactivity against band 3 protein probably indicates recognition of senescent RBC. Proteins uniquely recognized by antibodies in dogs with IMHA are involved in oxidative stress and apoptosis (calpain), inflammation (complement), and scavenging of reactive oxygen species (peroxiredoxin 2). It remains to be determined if these proteins are important in initiating autoimmunity or if immunoglobulins targeting these proteins develop during IMHA. PMID- 22315968 TI - Development of new demi-span equations from a nationally representative sample of older people to estimate adult height. AB - OBJECTIVES: To develop new equations for the calculation of body mass index (BMI) of adults aged 65 and older for when an actual height measurement may not be possible or reflect attained height because of loss of height with aging or conditions such as kyphosis or osteoporosis. DESIGN: Cross-sectional, nationally representative samples; data from 1994, 2000 2005, and 2007. SETTING: Adults aged 65 and older living in England. PARTICIPANTS: Two thousand four hundred fifty four noninstitutitionalized adults aged 65 and older taking part in the Health Survey for England (HSE). MEASUREMENTS: Height and demi-span measurements (defined as the distance between the mid-point of the sternal notch and the finger roots with the arm outstretched laterally) were taken according to standard procedures. RESULTS: Sex- and age-specific regression equations were produced from measured height and demi-span (DEH) using HSE 2005 data to develop new DEH equations (DEH(age)) from people aged 65 and older. The derived DEH(age) equation was applied to the HSE data for 1994, 2000, and 2007 to attempt to test its reliability. Analysis showed that DEH(age) predicts current height better than when using the Bassey equation (DEH(B) (assey)). DEH(age) can be used instead of a height measurement to derive other anthropometric indices such as body mass index (BMI) in older people. CONCLUSION: The new equations developed for predicting current height in older people can be used to calculate BMI more accurately in older people. PMID- 22315969 TI - A general lithography-free method of microscale/nanoscale fabrication and patterning on Si and Ge surfaces. AB - Here, we introduce and give an overview of a general lithography-free method to fabricate silicide and germanide micro-/nanostructures on Si and Ge surfaces through metal-vapor-initiated endoepitaxial growth. Excellent controls on shape and orientation are achieved by adjusting the substrate orientation and growth parameters. Furthermore, micro-/nanoscale pits with controlled morphologies can also be successfully fabricated on Si and Ge surfaces by taking advantage of the sublimation of silicides/germanides. The aim of this brief report is to illustrate the concept of lithography-free synthesis and patterning on surfaces of elemental semiconductors, and the differences and the challenges associated with the Si and the Ge surfaces will be discussed. Our results suggest that this low-cost bottom-up approach is promising for applications in functional nanodevices. PMID- 22315970 TI - Effects of partner proteins on BCA2 RING ligase activity. AB - BACKGROUND: BCA2 is an E3 ligase linked with hormone responsive breast cancers. We have demonstrated previously that the RING E3 ligase BCA2 has autoubiquitination activity and is a very unstable protein. Previously, only Rab7, tetherin, ubiquitin and UBC9 were known to directly interact with BCA2. METHODS: Here, additional BCA2 binding proteins were found using yeast two-hybrid and bacterial-II-hybrid screening techniques with Human breast and HeLa cDNA libraries. Co-expression of these proteins was analyzed through IHC of TMAs. Investigation of the molecular interactions and effects were examined through a series of in vivo and in vitro assays. RESULTS: Ten unique BCA2 interacting proteins were identified, two of which were hHR23a and 14-3-3sigma. Both hHR23a and 14-3-3sigma are co-expressed with BCA2 in breast cancer cell lines and patient breast tumors (n = 105). hHR23a and BCA2 expression was significantly correlated (P = < 0.0001 and P = 0.0113) in both nucleus and cytoplasm. BCA2 expression showed a statistically significant correlation with tumor grade. High cytoplasmic hHR23a trended towards negative nodal status. Binding to BCA2 by hHR23a and 14-3-3sigma was confirmed in vitro using tagged partner proteins and BCA2. hHR23a and 14-3-3sigma effect the autoubiquitination and auto-degradation activity of BCA2. Ubiquitination of hHR23a-bound BCA2 was found to be dramatically lower than that of free BCA2, suggesting that hHR23a promotes the stabilization of BCA2 by inactivating its autoubiquitination activity, without degradation of hHR23a. On the other hand, phosphorylated BCA2 protein is stabilized by interaction with 14-3-3sigma both with and without proteasome inhibitor MG-132 suggesting that BCA2 is regulated by multiple degradation pathways. CONCLUSIONS: The interaction between BCA2 and hHR23a in breast cancer cells stabilizes BCA2. High expression of BCA2 is correlated with grade in breast cancer, suggesting regulation of this E3 ligase is important to cancer progression. PMID- 22315971 TI - Redox proteomics analyses of the influence of co-expression of wild-type or mutated LRRK2 and Tau on C. elegans protein expression and oxidative modification: relevance to Parkinson disease. AB - AIMS: The human LRRK2 gene has been identified as the most common causative gene of autosomal-dominantly inherited and idiopathic Parkinson disease (PD). The G2019S substitution is the most common mutation in LRRK2. The R1441C mutation also occurs in cases of familial PD, but is not as prevalent. Some cases of LRRK2 based PD exhibit Tau pathology, which suggests that alterations on LRRK2 activity affect the pathophysiology of Tau. To investigate how LRRK2 might affect Tau and the pathophysiology of PD, we generated lines of C. elegans expressing human LRRK2 [wild-type (WT) or mutated (G2019S or R1441C)] with and without V337M Tau. Expression and redox proteomics were used to identify the effects of LRRK2 (WT and mutant) on protein expression and oxidative modifications. RESULTS: Co expression of WT LRRK2 and Tau led to increased expression of numerous proteins, including several 60S ribosomal proteins, mitochondrial proteins, and the V-type proton ATPase, which is associated with autophagy. C. elegans expressing mutant LRRK2 showed similar changes, but also showed increased protein oxidation and lipid peroxidation, the latter indexed as increased protein-bound 4-hydroxy-2 nonenal (HNE). INNOVATION: Our study brings new knowledge about the possible alterations induced by LRRK2 (WT and mutated) and Tau interactions, suggesting the involvement of G2019S and R1441C in Tau-dependent neurodegenerative processes. CONCLUSION: These results suggest that changes in LRRK2 expression or activity lead to corresponding changes in mitochondrial function, autophagy, and protein translation. These findings are discussed with reference to the pathophysiology of PD. PMID- 22315972 TI - Key signaling nodes in mammary gland development and cancer: Smad signal integration in epithelial cell plasticity. AB - Smad proteins are the key intermediates of transforming growth factor-beta (TGF beta) signaling during development and in tissue homeostasis. Pertubations in TGF beta/Smad signaling have been implicated in cancer and other diseases. In the cell nucleus, Smad complexes trigger cell type- and context-specific transcriptional programs, thereby transmitting and integrating signals from a variety of ligands of the TGF-beta superfamily and other stimuli in the cell microenvironment. The actual transcriptional and biological outcome of Smad activation critically depends on the genomic integrity and the modification state of genome and chromatin of the cell. The cytoplasmic and nuclear Smads can also modulate the activity of other signal transducers and enzymes such as microRNA processing factors. In the case of breast cancer, the role of Smads in epithelial plasticity, tumor-stroma interactions, invasion, and metastasis seems of particular importance. PMID- 22315973 TI - WldS but not Nmnat1 protects dopaminergic neurites from MPP+ neurotoxicity. AB - BACKGROUND: The WldS mouse mutant ("Wallerian degeneration-slow") delays axonal degeneration in a variety of disorders including in vivo models of Parkinson's disease. The mechanisms underlying WldS -mediated axonal protection are unclear, although many studies have attributed WldS neuroprotection to the NAD+ synthesizing Nmnat1 portion of the fusion protein. Here, we used dissociated dopaminergic cultures to test the hypothesis that catalytically active Nmnat1 protects dopaminergic neurons from toxin-mediated axonal injury. RESULTS: Using mutant mice and lentiviral transduction of dopaminergic neurons, the present findings demonstrate that WldS but not Nmnat1, Nmnat3, or cytoplasmically targeted Nmnat1 protects dopamine axons from the parkinsonian mimetic N-methyl-4 phenylpyridinium (MPP+). Moreover, NAD+ synthesis is not required since enzymatically-inactive WldS still protects. In addition, NAD+ by itself is axonally protective and together with WldS is additive in the MPP+ model. CONCLUSIONS: Our data suggest that NAD+ and WldS act through separate and possibly parallel mechanisms to protect dopamine axons. As MPP+ is thought to impair mitochondrial function, these results suggest that WldS might be involved in preserving mitochondrial health or maintaining cellular metabolism. PMID- 22315974 TI - Fluoride content of solid foods impacts daily intake. AB - OBJECTIVE: To determine the amount of fluoride received from solid foods for a cohort of children. METHODS: Parents were asked to complete questionnaires for the preceding week and dietary diaries for 3 days for their children. Data collected at 6, 9, 12, 16, 20, 24, 36, 48, and 60 months were analyzed cross sectionally. RESULTS: At 6 months of age, children ingested an estimated mean of 8 percent of dietary fluoride from solid foods. At 12 months of age, children ingested an estimated 39 percent of dietary fluoride from solid foods. Although the percentage of fluoride intake from solid foods stabilized from 24 to 60 months (means of 36-39 percent), some children received as much as 85-88 percent of their dietary fluoride from solid foods. CONCLUSIONS: Some children receive a substantial portion of dietary fluoride from solid foods. PMID- 22315975 TI - Rectangular-shaped expanded phthalocyanines with two central metal atoms. AB - Expanded phthalocyanine (Pc) congeners with two Mo or W central metal ions and four isoindole ring moieties have been synthesized using normal Pc formation conditions in the presence of urea. The products have been characterized by electrochemistry; mass spectrometry (MS); IR, electron paramagnetic resonance (EPR), NMR, electronic absorption, and magnetic circular dichroism (MCD) spectroscopies; and X-ray analysis. The X-ray structures have rectangular C(2v) symmetry and provide evidence that the central Mo atoms are linked by a single bond and coordinated by two isoindole nitrogen atoms and two nitrogen atoms from the amine moieties. The electronic absorption bands extend into the 1200-1500 nm region. This can be explained using Gouterman's four-orbital theory. The experimental NMR data and theoretical calculations provide evidence for a heteroaromatic 22-pi-electron conjugation system for the ring-expanded Pc system, which satisfies Huckel's (4n + 2)pi aromaticity. PMID- 22315978 TI - A peptide-embedded trifluoromethyl ketone catalyst for enantioselective epoxidation. AB - The development of peptide-based oxidation catalysts that use a transiently generated dioxirane as the chemically active species is reported. The active catalyst is a chiral trifluoromethyl ketone (Tfk) with a pendant carboxylic acid that can be readily incorporated into a peptide. These peptides were capable of epoxidizing alkenes in high yield (up to 89%) and enantiomeric ratios (er) ranging from 69.0:31.0 to 91.0:9.0, depending on the alkene substitution pattern. PMID- 22315979 TI - Does place of residence affect risk of suicide? a spatial epidemiologic investigation in Kentucky from 1999 to 2008. AB - BACKGROUND: Approximately 32,000 people take their own lives every year in the United States. In Kentucky, suicide mortality rates have been steadily increasing since 1999. Few studies in the United States have assessed spatial clustering of suicides. The purpose of this study was to identify high-risk clusters of suicide at the county level in Kentucky and assess the characteristics of those suicide cases within the clusters. METHODS: A spatial epidemiological study was undertaken using suicide data for the period January 1, 1999 to December 31, 2008, obtained from the Kentucky Office of Vital Statistics. Descriptive analyses using Pearson's chi-square test and t-test were performed to determine whether differences existed in age, marital status, year, season, and suicide method between males and females, and between cases inside and outside high-risk spatial clusters. Annual age-adjusted cumulative incidence rates were also calculated. Suicide incidence rates were spatially smoothed using the Spatial Empirical Bayesian technique. Kulldorff's spatial scan statistic was applied on all suicide cases at the county level to identify counties with the highest risks of suicide. Temporal cluster analysis was also performed. RESULTS: There were a total of 5,551 suicide cases in Kentucky from 1999 to 2008, of which 5,237 (94%) were included in our analyses. The majority of suicide cases were males (82%). The average age of suicide victims was 45.4 years. Two statistically significant (p < 0.05) high-risk spatial clusters, involving 15 counties, were detected. The county level cumulative incidence rate in the most likely high-risk cluster ranged from 12.4 to 21.6 suicides per 100,000 persons. The counties inside both high-risk clusters had relative risks ranging from 1.24 to 1.38. CONCLUSIONS: Statistically significant high-risk spatial clusters of suicide were detected at the county level. This study may be useful for guiding future research and intervention efforts. Future studies will need to focus on these high-risk clusters to investigate reasons for these occurrences. PMID- 22315980 TI - Effects of habitual physical activity on response to endurance training. AB - We hypothesised that habitual physical activity (PA) together with progressive endurance training contributes to the differences in training response (Delta[V(.)]O(2max)) in healthy and physically active male participants. Twenty volunteers (age 30+/-3 years and [V(.)]O(2max) 54+/-7 ml.kg-1.min-1) participated in an eight-week training program which included four to six heart rate-guided exercise sessions weekly. PA data over the whole period were collected by an accelerometer-equipped wristwatch. Individual relative intensities of endurance training and PA were separately determined by adjusting to [V(.)]O(2max) reserve and calculated as mean daily duration (min) of training and PA at light, moderate, high and very high intensity levels. [V(.)]O(2max) increased 6.4+/-4.1% (p < 0.0001) during the training period. Delta[V(.)]O(2max) correlated with the amount of habitual PA that was mainly of light intensity (r = 0.53, p = 0.016), but not with the duration of moderate, high or very high intensity PA (p = ns for all). Age, body mass index, and daily amount of training at any intensity level of exercise were not related to Delta[V(.)]O(2max) (p = ns for all). In conclusion, a high amount of habitual PA together with prescribed endurance training was associated with good training response in physically active males. PMID- 22315981 TI - Discovery of LFF571: an investigational agent for Clostridium difficile infection. AB - Clostridium difficile (C. difficile) is a Gram positive, anaerobic bacterium that infects the lumen of the large intestine and produces toxins. This results in a range of syndromes from mild diarrhea to severe toxic megacolon and death. Alarmingly, the prevalence and severity of C. difficile infection are increasing; thus, associated morbidity and mortality rates are rising. 4-Aminothiazolyl analogues of the antibiotic natural product GE2270 A (1) were designed, synthesized, and optimized for the treatment of C. difficile infection. The medicinal chemistry effort focused on enhancing aqueous solubility relative to that of the natural product and previous development candidates (2, 3) and improving antibacterial activity. Structure-activity relationships, cocrystallographic interactions, pharmacokinetics, and efficacy in animal models of infection were characterized. These studies identified a series of dicarboxylic acid derivatives, which enhanced solubility/efficacy profile by several orders of magnitude compared to previously studied compounds and led to the selection of LFF571 (4) as an investigational new drug for treating C. difficile infection. PMID- 22315982 TI - Redox balance- and radiation-mediated alteration in hippocampal neurogenesis. AB - Changes in the intracellular and extracellular redox balance have been correlated with cell fate decisions in terms of proliferation versus differentiation, entering versus existing cell cycle and survival versus cell death. Adult hippocampal neurogenesis has been correlated with neuronal plasticity of learning and memory; however, the process is exquisitely sensitive to changes in redox balance. Cranial irradiation is an effective modality in treating brain tumours but often leads to deficits in hippocampus-related learning and memory, which is most likely due to sustained elevation of oxygen free radical production and suppression of hippocampal neurogenesis. The subcellular redox environment affecting hippocampal neurogenesis is largely unknown. Using mutant mice deficient in each one of the three superoxide dismutase (SOD, EC 1.15.1.1) isoforms, we have begun to determine the consequences of SOD deficiency in hippocampal neurogenesis and the related functions of learning and memory under normal condition and following cranial irradiation. PMID- 22315983 TI - Effects of growth hormone deficiency on body composition and biomarkers of cardiovascular risk after definitive therapy for acromegaly. AB - BACKGROUND: Both growth hormone (GH) excess and GH deficiency are associated with abnormalities in body composition and biomarkers of cardiovascular risk in patients with pituitary disorders. However, the effects of developing GH deficiency after definitive treatment of acromegaly are largely unknown. OBJECTIVE: To determine whether development of GH deficiency after definitive therapy for acromegaly is associated with increased visceral adiposity and biomarkers of cardiovascular risk compared with GH sufficiency after definitive therapy for acromegaly. DESIGN: Cross-sectional. PATIENTS: We studied three groups of subjects, all with a history of acromegaly (n = 76): subjects with subsequent GH deficiency (GHD; n = 31), subjects with subsequent GH sufficiency (GHS; n = 25) and subjects with active acromegaly (AA; n = 20). No study subjects were receiving somatostatin analogues, dopamine agonists or hGH. MEASUREMENTS: Body composition (by DXA), abdominal adipose tissue depots (by cross-sectional CT), total body water (by bioimpedance analysis) and carotid intima-media thickness (IMT) were measured. Fasting morning serum was collected for high sensitivity C-reactive protein (hsCRP), lipids and lipoprotein levels. An oral glucose tolerance test was performed, and homoeostasis model of assessment insulin resistance (HOMA-IR) was calculated. RESULTS: Abdominal visceral adipose tissue, total adipose tissue and total body fat were higher in subjects with GHD than GHS or AA (P < 0.05). Subcutaneous abdominal fat was higher, and fibrinogen and IMT were lower in GHD (but not GHS) than AA (P < 0.05). Patients with GHD had the highest hsCRP, followed by GHS, and hsCRP was lowest in AA (P < 0.05). Fasting glucose, 120-min glucose, fasting insulin, HOMA-IR and per cent total body water were lower in GHD and GHS than AA (P < 0.05). Triglycerides were higher in GHS than AA (P < 0.05). Lean body mass, mean arterial pressure, total cholesterol, HDL and LDL were comparable among groups. CONCLUSIONS: Development of GHD after definitive treatment of acromegaly may adversely affect body composition and inflammatory biomarkers of cardiovascular risk but does not appear to adversely affect glucose homoeostasis, lipids and lipoproteins, or other cardiovascular risk markers. PMID- 22315984 TI - Ambroxol influences voriconazole resistance of Candida parapsilosis biofilm. AB - The ability to form biofilm on different surfaces is typical of most Candida species. Microscopic structure and genetic aspects of fungal biofilms have been the object of many studies because of very high resistance to antimycotic agents because of the scarce permeability of the external matrix and to the alterations in cell metabolism. In our study, 31 isolates of Candida parapsilosis, isolated from bloodstream infections, were tested for their ability to produce biofilm and were found to be good producers. The susceptibility to voriconazole, assayed by colorimetrical XTT assay, revealed a very elevated minimum inhibitory concentrations for sessile cells in comparison with planktonic ones. The addition of ambroxol, a mucolytic agent, increased the susceptibility of biofilm forming cells to voriconazole. Expression of the efflux pump genes CDR and MDR was analyzed in biofilms alone or treated with ambroxol, evidencing a role of ambroxol in the expression of genes involved in azole resistance mechanisms of C. parapsilosis biofilms. In conclusion, our data seem to encourage the use of different substances in combination with classical antimycotics, with the aim of finding a solution to the increasing problem of the resistance of biofilms formed on medical devices by nonalbicans Candida species. PMID- 22315985 TI - Could receptors for advanced glycation end products be considered cardiovascular risk markers in obese children? AB - Early development of increased cardiovascular risk in obese children and the possible related cardiovascular diseases into adulthood have been shown; however, the underling pathogenetic mechanisms implicated are not yet completely defined. Receptors for advanced glycation end products (RAGE) pathway play a pivotal role in the genesis of abnormality of arterial wall. However, whether obese prepubertal children present impaired levels of endogenous and soluble secretory receptor for advanced glycation end products (esRAGE/sRAGE) and whether an association exists between RAGE levels and carotid intima media thickness (cIMT) are not yet evaluated in this age group. We note that esRAGE and sRAGE were significantly lower in obese children than controls and were independently related to cIMT. Our findings lead to the hypothesis that RAGE system seems to be related to the development of atherosclerosis even in obese prepubertal children. PMID- 22315988 TI - Effects of parameter manipulations on spread of excitation measured with electrically-evoked compound action potentials. AB - OBJECTIVE: This study investigated the spread of excitation (SOE) profiles derived by eCAP measures and analysed the effects of various parameter settings. DESIGN: SOE was measured using the forward masking technique (selectivity), as well as with a "fixed stimulus, variable recording" (scanning) technique. SOE profiles were produced at three current levels and at three sites along the array. Additionally, effects of the position of the recording electrodes and artefact rejection methods were studied in five subjects. Furthermore, correlation between SOE data and speech perception data was tested. All data were analysed using linear mixed models. STUDY SAMPLE: Measurements were performed intraoperatively in 31 users of the Advanced Bionics HiRes 90K cochlear implant. RESULTS: The selectivity method produced narrower excitation profiles than the scanning method, showing an asymmetry along the array with wider SOE apically. Moreover, the position of the recording electrode shifted the SOE curves towards the recording contact, enhancing asymmetry. Neither significant effects of current level or artefact rejection methods were observed, nor a significant correlation with speech perception. CONCLUSIONS: SOE profiles obtained with the scanning method are wider than with the selectivity method. Both are insensitive to various parameter settings, although selectivity curves are shifted towards the recording contact. PMID- 22315989 TI - Diabetes mellitus: prevalence and effect of morbidities in the oldest old. The Octabaix study. AB - OBJECTIVES: To describe the prevalence of diabetes mellitus (DM) in community dwelling 85-year-olds and to study the factors associated. DESIGN: Cross sectional. SETTING: Community-based survey study of seven primary healthcare centers. PARTICIPANTS: Three hundred twenty-eight people born in 1924 and registered with primary healthcare centers. MEASUREMENTS: Information on sociodemographic variables, Barthel Index (BI), Spanish version of the Mini Mental State Examination (MEC), Mini Nutritional Assessment (MNA), Braden scale for risk of pressure ulcers, Charlson Comorbidity Index, chronic diseases, social risk, quality of life, chronic drug prescriptions, and blood tests was recorded. Participants were defined as having DM according to self-report, physician diagnosis, antidiabetic prescriptions, or plasma glucose concentration 7 mmol/L or more. A comparative analysis was performed between participants with and without DM. RESULTS: The prevalence of DM in 328 octogenarians studied was 25.9%. Logistic regression showed an association between DM and BI (odds ratio (OR) = 1.03, 95% confidence interval (CI) = 1.00-1.05, P = .007), Braden risk score (OR = 0.87, 95% CI = 0.79-0.97, P = .01), thyroid disease (OR = 0.23, 95% CI = 0.06 0.92, P = .04), chronic drug prescriptions (OR = 1.28, 95% CI = 1.15-1.42, P < .001), white-cell count (OR = 1.34, 95% CI = 1.15-1.56, P < .001), low-density lipoprotein cholesterol (LDL-C; OR = 0.63, 95% CI = 0.43-0.92, P = .02) and folic acid level (OR = 1.04, 95% CI = 1.01-1.07, P = .005). CONCLUSION: There is a high prevalence of DM at 85 years old. The presence of DM was positively associated with disability, drug prescription, white blood cell count, and folic acid level, whereas there was an inverse relationship between DM and Braden scale score, thyroid disease, and LDL-C. The effect of morbidities on DM may require a multidisciplinary approach to manage its complexity. PMID- 22315990 TI - Initiating breast cancer by PIK3CA mutation. AB - PIK3CA mutations confer constitutive activation of PI3K, which initiates intracellular kinase signaling cascades that promote cell proliferation and survival. Recent studies by Meyer and colleagues, and Liu and colleagues demonstrate that expression of the H1047R exon 20 mutant of PIK3CA in luminal mammary epithelial cells induces tumorigenesis, implying that PIK3CA mutation is an early event in breast cancer. PIK3CA-H1047R-initiated tumors exhibit variable dependence on the oncogene and variable sensitivity to PI3K inhibition. Amplification of the oncogenes MYC and MET was observed in tumors that recurred following silencing of PIK3CA-H1047R, suggesting that these pathways represent mechanisms of escape from PI3K inhibition. PMID- 22315991 TI - 12-hydroxy-1-azaperylene-limiting case of the ESIPT system: enol-keto tautomerization in S0 and S1 states. AB - Absorption, fluorescence, and fluorescence excitation spectra of 12-hydroxy-1 azaperylene (HAP) and 1-azaperylene were studied in n-alkane matrices at 5 K. Two stable tautomers of HAP, each of them in n-nonane embedded in two sites, were identified and attributed to the enol and keto forms. Theoretical calculations of the energy and vibrational structure of the spectra suggest that tautomer A, with the (0, 0) transition energy at 18,980 +/- 10 cm(-1) (and 19,060 +/- 10 cm(-1) in the high energy site), should be identified as the keto form, whereas tautomer B, with the (0, 0) energy at 19,200 +/- 20 cm(-1) (19,290 +/- 20 cm(-1)), as the enol form. Observation of absorption and fluorescence of both tautomeric forms and lack of large Stokes shift of fluorescence of the keto form classify HAP as the limiting case of the excited-state intramolecular proton transfer system. PMID- 22315992 TI - Use of facile mechanochemical method to functionalize carbon nanofibers with nanostructured polyaniline and their electrochemical capacitance. AB - A facile approach to functionalize carbon nanofibers [CNFs] with nanostructured polyaniline was developed via in situ mechanochemical polymerization of polyaniline in the presence of chemically treated CNFs. The nanostructured polyaniline grafting on the CNF was mainly in a form of branched nanofibers as well as rough nanolayers. The good dispersibility and processability of the hybrid nanocomposite could be attributed to its overall nanostructure which enhanced its accessibility to the electrolyte. The mechanochemical oxidation polymerization was believed to be related to the strong Lewis acid characteristic of FeCl3 and the Lewis base characteristic of aniline. The growth mechanism of the hierarchical structured nanofibers was also discussed. After functionalization with the nanostructured polyaniline, the hybrid polyaniline/CNF composite showed an enhanced specific capacitance, which might be related to its hierarchical nanostructure and the interaction between the aromatic polyaniline molecules and the CNFs. PMID- 22315993 TI - Efficient degradation of TCE in groundwater using Pd and electro-generated H2 and O2: a shift in pathway from hydrodechlorination to oxidation in the presence of ferrous ions. AB - Degradation of trichloroethylene (TCE) in simulated groundwater by Pd and electro generated H(2) and O(2) is investigated in the absence and presence of Fe(II). In the absence of Fe(II), hydrodechlorination dominates TCE degradation, with accumulation of H(2)O(2) up to 17 mg/L. Under weak acidity, low concentrations of oxidizing *OH radicals are detected due to decomposition of H(2)O(2), slightly contributing to TCE degradation via oxidation. In the presence of Fe(II), the degradation efficiency of TCE at 396 MUM improves to 94.9% within 80 min. The product distribution proves that the degradation pathway shifts from 79% hydrodechlorination in the absence of Fe(II) to 84% *OH oxidation in the presence of Fe(II). TCE degradation follows zeroth-order kinetics with rate constants increasing from 2.0 to 4.6 MUM/min with increasing initial Fe(II) concentration from 0 to 27.3 mg/L at pH 4. A good correlation between TCE degradation rate constants and *OH generation rate constants confirms that *OH is the predominant reactive species for TCE oxidation. Presence of 10 mM Na(2)SO(4), NaCl, NaNO(3), NaHCO(3), K(2)SO(4), CaSO(4), and MgSO(4) does not significantly influence degradation, but sulfite and sulfide greatly enhance and slightly suppress degradation, respectively. A novel Pd-based electrochemical process is proposed for groundwater remediation. PMID- 22315994 TI - Long term effects of tetramine poisoning: an observational study. AB - CONTEXT: Tetramine is an illegal rat poison that has resulted in a number of accidental mass poisonings in China. OBJECTIVE: To investigate the long term outcome of tetramine poisoning. MATERIALS AND METHODS: A survey of epileptic attacks in 370 patients in the Hubei province of P. R. China who had survived tetramine poisoning in the last decade was undertaken by means of telephone calls, letters, and interviews. Data describing the initial acute episode was gathered from medical and public health records. RESULTS: Among the 370 patients surveyed (188 males, 182 females, age range 10 to 71 y), 352 experienced seizures during the initial poisoning. One hundred fifty-eight individuals are currently seizure-free, after an average medication period of 2.93 years. The other patients have recurrent epilepsy, including 156 with tonic-clonic seizures and 39 with partial seizures. Six patients have other neurological problems. DISCUSSION AND CONCLUSION: Tetramine, a rat poison sometimes ingested by mistake, blocks GABA receptors and causes seizures. These seizures can persist for years after the initial poisoning, even when no seizures are present initially. Sodium valproate, which has the ability to increase the amount of GABA in the CNS, would be a reasonable choice for the treatment of epilepsy caused by tetramine poisoning. PMID- 22315995 TI - Rhabdomyolysis, methemoglobinemia and acute kidney injury after indoxacarb poisoning. PMID- 22315996 TI - Social acceptability of dental appearance and benefits of fixed orthodontic treatment: a 17-year observational cohort study. AB - OBJECTIVES: This study reports on the social acceptability of dental appearance and benefits of fixed orthodontic treatment (FOT) among a cohort of 13-year-old adolescents in 1988/1989 followed through to age 30 years in 2005/2006. METHODS: Adolescents were categorized into nominal treatment need groups based on the dental aesthetic index (DAI) score at age 13 (DAI: <= 25 "No Need"; 26-30, "Elective"; 31-35, "Desirable"; and >=36, "Mandatory"). At age 30, calibrated examiners again assessed the DAI of traced participants. A reduction in the baseline DAI score of at least five units was considered a benefit. The change in DAI scores was examined by receipt of FOT. The number needed to treat (NNT) was estimated as an indicator of the efficacy of FOT. RESULTS: Of the 421 cohort participants examined at follow-up, 148 had undergone FOT; 34 percent of those with FOT were classified at age 13 as "No Need" (n = 50); 21 percent as "Elective" (n = 31); 17 percent as "Desirable" (n = 26); and 28 percent as "Mandatory Need" (n = 41). The DAI score reduced significantly for those with and without FOT. The NNT from FOT for those individuals in the "No Need" category was 17 [95 percent confidence interval (CI) - 26-6]; "Elective" 6 (95 percent CI - 27 3); "Desirable" 5 (95 percent CI 3-51) and "Mandatory Need" 14 (95 percent CI - 16-4). CONCLUSIONS: FOT provided a significant benefit only for individuals in the "Desirable" group at age 13. FOT appeared to offer little long-term benefits in the social acceptability of dental appearance for the majority of individuals who underwent FOT. PMID- 22315997 TI - Too close to home? Experiences of Kurdish refugee interpreters working in UK mental health services. AB - BACKGROUND: Despite their essential role in the National Health Service, there is limited research on the experiences of refugee interpreters. AIMS: To explore Kurdish refugee interpreters' experiences of working in UK mental health services. METHOD: Six participants were interviewed and data collected were analysed using interpretative phenomenological analysis. RESULTS: The results showed that interpreters often felt overwhelmed by the emotional impact of interpreting in mental health services, particularly at the beginning of their careers. Interpreters struggled to negotiate complex and unclear roles and responsibilities. Interpreting for refugees with shared histories was particularly challenging. CONCLUSIONS: The study recommends that interpreters working in mental health services receive training on mental health issues and self-care and are assisted by frameworks to help make sense of the impact of the work, such as supervision. PMID- 22315998 TI - Conformation types of ubiquitin [M+8H]8+ Ions from water:methanol solutions: evidence for the N and A States in aqueous solution. AB - Ion mobility and mass spectrometry measurements are used to examine the gas-phase populations of [M+8H](8+) ubiquitin ions formed upon electrospraying 20 different solutions from 100:0 to 5:95 water:methanol that are maintained at pH = 2.0. Over this range of solution conditions, mobility distributions for the +8 charge state show substantial variations. Here we develop a model that treats the combined measurements as one data set. By varying the relative abundances of a discrete set of conformation types, it is possible to represent distributions obtained from any solution. For solutions that favor the well-known A-state ubiquitin, it is possible to represent the gas-phase distributions with seven conformation types. Aqueous conditions that favor the native structure require four more structural types to represent the distribution. This analysis provides the first direct evidence for trace amounts of the A state under native conditions. The method of analysis presented here should help illuminate how solution populations evolve into new gas-phase structures as solvent is removed. Evidence for trace quantities of previously unknown states under native solution conditions may provide insight about the relationship of dynamics to protein function as well as misfolding and aggregation phenomena. PMID- 22316000 TI - One metabolite, two pathways: convergence of polypropionate biosynthesis in fungi and marine molluscs. AB - Structural similarity or even the identity of polyketide compounds does not necessarily imply unique biosynthesis. Feeding experiments with a (13)C labeled precursor establish that the C(3) units in 7-methyl-cyercene-1 (1) are derived from intact propionate in the marine mollusc Ercolania funerea. The same compound in the terrestrial fungus Leptosphaeria maculans/Phoma lingam is synthesized by an acetate/SAM pathway thus proving for the first time metabolic convergence of polyketide biosynthesis in eukaryotes. Traditional (1)H-(13)C NMR correlation spectroscopy has been successfully applied to estimate (13)C incorporation in biosynthetic experiments. PMID- 22315999 TI - Spinal cord trauma and the molecular point of no return. AB - A mechanical trauma to the spinal cord can be followed by the development of irreversible and progressive neurodegeneration, as opposed to a temporary or partially reversible neurological damage. An increasing body of experimental and clinical evidence from humans and animal models indicates that spinal cord injury may set in motion the development of disabling and at times fatal neuromuscular disorders, whose occurrence is not normally associated with any major environmental event. This outcome appears to be dependent on the co-occurrence of a particular form of mechanical stress and of a genetically-determined vulnerability. This increased vulnerability to spinal cord injury may depend on a change of the nature and of the timing of activation of a number of neuroprotective and neurodestructive molecular signals in the injured cord. Among the main determinants, we could mention an altered homeostasis of lipids and neurofilaments, an earlier inflammatory response and the failure of the damaged tissue to rein in oxidative damage and apoptotic cell death. These changes could force injured tissue beyond a point of no return and precipitate an irreversible neurodegenerative process. A better knowledge of the molecular signals activated in a state of increased vulnerability to trauma can inform future treatment strategies and the prediction of the neurological outcome after spinal cord injury. PMID- 22316001 TI - Two new triterpenoid glycosides from Curculigo orchioides. AB - Two new cycloartane triterpenoid glycosides, named curculigosaponin N and curculigosaponin O, were isolated from rhizomes of Curculigo orchioides Gaertn. Their structures were elucidated on the basis of comprehensive spectroscopic analysis including IR, MS, 1D, and 2D NMR (HSQC and HMBC). PMID- 22316002 TI - Extracellular matrix alterations in experimental Leishmania amazonensis infection in susceptible and resistant mice. AB - Leishmania is inoculated, by the bite of an infected sandfly, into the skin of the host, where the promastigotes are phagocyted by dermal macrophages. The dermal region comprises cells and abundant extracellular matrix. Studies show that matrix metalloproteinases play an important role in host defense responses against pathogens in mammals and that their activities lead to the production of antimicrobial peptides. The aim of this study is to evaluate the changes in the distribution of fibronectin and laminin as well as in the elastic system fibres during the course of infection caused by Leishmania amazonensis in mice with distinct genetic backgrounds of susceptibility to this parasite. The results showed that BALB/c presented an enhancement of fibronectin during the course of infection when compared to their control group while the infected or non-infected C3H.He showed a decrease of this protein at end of the experiment. Laminin, on the other hand, remained unaltered in both strains. Also in both BALB/c and C3H.He mice the elastic and elaunin fibres remained unchanged while the oxytalan fibres decreased along the experiment. Ninety days after the infection C3H.He mice had recovered their capacity to produce oxytalan fibres. PMID- 22316003 TI - Research, evidence and policymaking: the perspectives of policy actors on improving uptake of evidence in health policy development and implementation in Uganda. AB - BACKGROUND: Use of evidence in health policymaking plays an important role, especially in resource-constrained settings where informed decisions on resource allocation are paramount. Several knowledge translation (KT) models have been developed, but few have been applied to health policymaking in low income countries. If KT models are expected to explain evidence uptake and implementation, or lack of it, they must be contextualized and take into account the specificity of low income countries for example, the strong influence of donors. The main objective of this research is to elaborate a Middle Range Theory (MRT) of KT in Uganda that can also serve as a reference for other low- and middle income countries. METHODS: This two-step study employed qualitative approaches to examine the principal barriers and facilitating factors to KT. Step 1 involved a literature review and identification of common themes. The results informed the development of the initial MRT, which details the facilitating factors and barriers to KT at the different stages of research and policy development. In Step 2, these were further refined through key informant interviews with policymakers and researchers in Uganda. Deductive content and thematic analysis was carried out to assess the degree of convergence with the elements of the initial MRT and to identify other emerging issues. RESULTS: Review of the literature revealed that the most common emerging facilitating factors could be grouped under institutional strengthening for KT, research characteristics, dissemination, partnerships and political context. The analysis of interviews, however, showed that policymakers and researchers ranked institutional strengthening for KT, research characteristics and partnerships as the most important. New factors emphasized by respondents were the use of mainstreamed structures within MoH to coordinate and disseminate research, the separation of roles between researchers and policymakers, and the role of the community and civil society in KT. CONCLUSIONS: This study refined an initial MRT on KT in policymaking in the health sector in Uganda that was based on a literature review. It provides a framework that can be used in empirical research of the process of KT on specific policy issues. PMID- 22316004 TI - Circles on pommel horse with a suspended aid: influence of expertise. AB - In the third study of this series, we examined how circles with a suspended aid would vary depending of the gymnast's level of expertise. We analysed circles with the aid performed by three groups of eight gymnasts: expert, intermediate, and developing groups. The gymnasts for the expert and intermediate groups were selected from the previous studies based on judges' evaluation of their non-aid circles. The developing group of eight gymnasts, who were unable to perform circles on pommel horse without an aid, were added to this study and performed three sets of 10 circles on the pommel horse with the aid. Discriminative biomechanical variables identified in the previous two studies were used to compare circles with the aid among the three groups. As a result, the expert group demonstrated a larger pommel reaction force and a smaller aid reaction force than the other two groups, implying that they were less dependent on the aid. The smaller aid reaction force resulted in a smaller net hip joint moment. Furthermore, the expert group showed a shorter total duration and a greater shoulder excursion. In summary, the suspended aid can be used in a progressive manner depending on the gymnast's level of expertise. PMID- 22316005 TI - Reactive oxygen species in cancer stem cells. AB - SIGNIFICANCE: Reactive oxygen species (ROS), byproducts of aerobic metabolism, are increased in many types of cancer cells. Increased endogenous ROS lead to adaptive changes and may play pivotal roles in tumorigenesis, metastasis, and resistance to radiation and chemotherapy. In contrast, the ROS generated by xenobiotics disturb the redox balance and may selectively kill cancer cells but spare normal cells. RECENT ADVANCES: Cancer stem cells (CSCs) are integral parts of pathophysiological mechanisms of tumor progression, metastasis, and chemo/radio resistance. Currently, intracellular ROS in CSCs is an active field of research. CRITICAL ISSUES: Normal stem cells such as hematopoietic stem cells reside in niches characterized by hypoxia and low ROS, both of which are critical for maintaining the potential for self-renewal and stemness. However, the roles of ROS in CSCs remain poorly understood. FUTURE DIRECTIONS: Based on the regulation of ROS levels in normal stem cells and CSCs, future research may evaluate the potential therapeutic application of ROS elevation by exogenous xenobiotics to eliminate CSCs. PMID- 22316006 TI - Predictors of pain associated with routine procedures performed in general dental practice. AB - OBJECTIVES: The objective of the study was to investigate factors that influence pain intensities associated with routine dental procedures. METHOD: Four hundred and fifty-one dental patients self-reported pain experienced during the procedure immediately after undergoing a variety of common dental interventions and 1 day after the completion of the procedure. Pain character was measured using the McGill short-form pain questionnaire and intensity using a numerical rating (NRS) scale. Information was collected on a number of factors that could influence pain: dental anxiety was measured using the Corah Dental Anxiety Scale to categorize patients into four domains (fearless, some unease, nervous and very anxious). Dentists provided information regarding the type(s) of procedure and use of local anaesthetic (LA). RESULTS: Seventy-five percent of patients (339/451) reported no pain during their procedure when the data were collected immediately postoperatively (NRS score = 0). Univariate analyses showed that dental anxiety, LA use and type of procedure (extractions) were significant (P < 0.05) predictors of reported intra-operative pain. However, when these factors were combined in a multivariate model, the strongest predictor of pain was dental anxiety [odds ratio (OR) = 4.98 (95% CI 1.42-17.44)] and LA use [OR = 2.79 (95% CI 1.39-5.61)]. Although the strongest predictor of postoperative pain on the next day was pain reported during the procedure [OR = 5.85 (95% CI 2.71-12.64)], LA remained a significant predictor of pain the day after the procedure [OR = 3.16 (95% CI 1.02-9.81)]. CONCLUSIONS: Dentists need to assess their patients both preoperatively for dental anxiety and intra-operatively for signs of suboptimal local anaesthesia so as to effectively align patient management and clinical techniques to control dental anxiety and produce adequate anaesthesia. PMID- 22316007 TI - Measurement and prediction of the acceptable noise level for single-microphone noise reduction algorithms. AB - OBJECTIVE: To measure the acceptable noise level (ANL) with and without noise reduction algorithms (NRAs), and to predict DeltaANL, i.e. the difference in acceptable noise level with and without NRAs. DESIGN: The ANL test was applied to three NRAs. Furthermore, the measured DeltaANL was predicted using several methods based on either the calculation of the signal-to-noise ratio or correlation methods of the processed signals with an unprocessed reference signal. STUDY SAMPLE: Ten normal-hearing and eleven hearing-impaired subjects accomplished the ANL test. RESULTS: In general, the ANL test could determine an increased acceptance of noise with some NRAs. However, great inter-individual differences also resulted that were attributed to audible distortions when an NRA was used. Prediction of the mean measured DANL was possible, but individual prediction of DANL failed due to inter-individual differences. Mean DANL was predicted more accurately for hearing-impaired subjects when individual hearing loss was taken into account. CONCLUSIONS: The ANL test is a suitable tool for measuring the advantage of one NRA. A prediction of the measured individual DeltaANL failed. However, mean DANL could be predicted with some methods. Furthermore, the individual hearing loss should be taken into account for a more accurate prediction for hearing-impaired subjects. PMID- 22316009 TI - P-glycoprotein-based loperamide-cyclosporine drug interaction at the rat blood brain barrier: prediction from in vitro studies and extrapolation to humans. AB - We have shown that the rat can quantitatively predict the verapamil-cyclopsorine A (CsA) drug-drug interaction (DDI) at the human blood-brain barrier (BBB). In addition, the potency (EC(50)) of CsA to inhibit rat BBB P-gp can be predicted from in vitro studies in MDRI-transfected cells. To assess if these excellent agreements extend to other substrates, we determined the magnitude of P-gp-based DDI at the rat BBB between loperamide (Lop) or its metabolite, N-desmethyl Lop (dLop), and escalating CsA blood concentrations. The percent increase in the brain:blood Lop concentration ratio was described by the Hill equation, E(max) = 2000%, EC(50) = 7.1 MUM and gamma = 3.7. The potency (EC(50)) of CsA to inhibit P gp at the rat BBB was independent of the substrate used (verapamil, Lop, or dLop). Like the verapamil-CsA DDI, the potency (EC(50)) of CsA to inhibit rat BBB P-gp could be predicted from studies in MDRI-transfected cells. When (11)C-Lop was coadministered with a 10 mg/kg iv infusion of CsA (1) yielding ~5.6 uM CsA blood concentration to healthy volunteers, the brain distribution of (11)C radioactivity was increased by 110%. (1) When corrected for diffusible Lop metabolite(s), this translates into an increase in (11)C-Lop brain distribution of 457%. Based on our rat data, we estimated a similar value at 5.6 MUM blood CsA concentration, 588% increase in Lop brain distribution. These data support our conclusion that the rat is a promising model to predict P-gp based DDI at the human BBB. PMID- 22316010 TI - Synthesis and evaluation of novel radioligands for positron emission tomography imaging of metabotropic glutamate receptor subtype 1 (mGluR1) in rodent brain. AB - We designed three novel positron emission tomography ligands, N-(4-(6 (isopropylamino)pyrimidin-4-yl)-1,3-thiazol-2-yl)-4-[(11)C]methoxy-N methylbenzamide ([(11)C]6), 4-[(18)F]fluoroethoxy-N-[4-[6 (isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([(18)F]7), and 4-[(18)F]fluoropropoxy-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2 yl]-N-methylbenzamide ([(18)F]8), for imaging metabotropic glutamate receptor type 1 (mGluR1) in rodent brain. Unlabeled compound 6 was synthesized by benzoylation of 4-pyrimidinyl-2-methylaminothiazole 10, followed by reaction with isopropylamine. Removal of the methyl group in 6 gave phenol precursor 12 for radiosynthesis. Two fluoroalkoxy analogues 7 and 8 were prepared by reacting 12 with tosylates 13 and 14. Radioligands [(11)C]6, [(18)F]7, and [(18)F]8 were synthesized by O-[(11)C]methylation or [(18)F]fluoroalkylation of 12. Compound 6 showed high in vitro binding affinity for mGluR1, whereas 7 and 8 had weak affinity. Autoradiography using rat brain sections showed that [(11)C]6 binding is aligned with the reported distribution of mGluR1 with high specific binding in the cerebellum and thalamus. PET study with [(11)C]6 in rats showed high brain uptake and a similar distribution pattern to that in autoradiography, indicating the usefulness of [(11)C]6 for imaging brain mGluR1. PMID- 22316012 TI - Uranium(VI) reduction by iron(II) monosulfide mackinawite. AB - Reaction of aqueous uranium(VI) with iron(II) monosulfide mackinawite in an O(2) and CO(2) free model system was studied by batch uptake measurements, equilibrium modeling, and L(III) edge U X-ray absorption spectroscopy (XAS). Batch uptake measurements showed that U(VI) removal was almost complete over the wide pH range between 5 and 11 at the initial U(VI) concentration of 5 * 10(-5) M. Extraction by a carbonate/bicarbonate solution indicated that most of the U(VI) removed from solution was reduced to nonextractable U(IV). Equilibrium modeling using Visual MINTEQ suggested that U was in equilibrium with uraninite under the experimental conditions. X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) spectroscopy showed that the U(IV) phase associated with mackinawite was uraninite. Oxidation experiments with dissolved O(2) were performed by injecting air into the sealed reaction bottles containing mackinawite samples reacted with U(VI). Dissolved U measurement and XAS confirmed that the uraninite formed from the U(VI) reduction by mackinawite did not oxidize or dissolve under the experimental conditions. This study shows that redox reactions between U(VI) and mackinawite may occur to a significant extent, implying an important role of the ferrous sulfide mineral in the redox cycling of U under sulfate reducing conditions. This study also shows that the presence of mackinawite protects uraninite from oxidation by dissolved O(2). The findings of this study suggest that uraninite formation by abiotic reduction by the iron sulfide mineral under low temperature conditions is an important process in the redistribution and sequestration of U in the subsurface environments at U contaminated sites. PMID- 22316013 TI - Studies of the gas phase reactions of linalool, 6-methyl-5-hepten-2-ol and 3 methyl-1-penten-3-ol with O3 and OH radicals. AB - The reactions of three unsaturated alcohols (linalool, 6-methyl-5-hepten-2-ol, and 3-methyl-1-penten-3-ol) with ozone and OH radicals have been studied using simulation chambers at T ~ 296 K and P ~ 760 Torr. The rate coefficient values (in cm(3) molecule(-1) s(-1)) determined for the three compounds are linalool, k(O3) = (4.1 +/- 1.0) * 10(-16) and k(OH) = (1.7 +/- 0.3) * 10(-10); 6-methyl-5 hepten-2-ol, k(O3) = (3.8 +/- 1.2) * 10(-16) and k(OH) = (1.0 +/- 0.3) * 10(-10); and 3-methyl-1-penten-3-ol, k(O3) = (5.2 +/- 0.6) * 10(-18) and k(OH) = (6.2 +/- 1.8) * 10(-11). From the kinetic data it is estimated that, for the reaction of O(3) with linalool, attack at the R-CH?C(CH(3))(2) group represents around (93 +/ 52)% (k(6-methyl-5-hepten-2-ol)/k(linalool)) of the overall reaction, with reaction at the R-CH?CH(2) group accounting for about (1.3 +/- 0.5)% (k(3-methyl 1-penten-3-ol)/k(linalool)). In a similar manner it has been calculated that for the reaction of OH radicals with linalool, attack of the OH radical at the R CH?C(CH(3))(2) group represents around (59 +/- 18)% (k(6-methyl-5-hepten-2 ol)/k(linalool)) of the total reaction, while addition of OH to the R-CH?CH(2) group is estimated to be around (36 +/- 6)% (k(3-methyl-1-penten-3 ol)/k(linalool)). Analysis of the products from the reaction of O(3) with linalool confirmed that addition to the R-CH?C(CH(3))(2) group is the predominant reaction pathway. The presence of formaldehyde and hydroxyacetone in the reaction products together with compelling evidence for the generation of OH radicals in the system indicates that the hydroperoxide channel is important in the loss of the biradical [(CH(3))(2)COO]* formed in the reaction of O(3) with linalool. Studies on the reactions of O(3) with the unsaturated alcohols showed that the yields of secondary organic aerosols (SOAs) are higher in the absence of OH scavengers compared to the yields in their presence. However, even under low NO(X) concentrations, the reactions of OH radicals with 3-methyl-1-penten-3-ol and 6-methyl-5-hepten-2-ol will make only a minor contribution to SOA formation under atmospheric conditions. Relatively high yields of SOAs were observed in the reactions of OH with linalool, although the initial concentrations of reactants were quite high. The importance of linalool in the formation of SOAs in the atmosphere requires further investigation. The impact following releases of these unsaturated alcohols into the atmosphere are discussed. PMID- 22316014 TI - Aerobic oxidations of C60(2-) in the presence of PhCN and PhCH2CN: oxygenation versus dehydrogenation reactions. AB - Aerobic oxidations of dianionic C(60) were examined in PhCN and PhCH(2)CN, where dioxygen was activated to O(2)(*-) via the single-electron transfer from C(60)(2 ) and underwent oxygenation and dehydrogenation reactions, respectively. Addition of PhCH(2)Br led to further benzylation for the oxygenated product but not for the dehydrogenated one, suggesting that the initial two negative charges were preserved for the intermediates of the oxygenation reaction but not for those of the dehydrogenation reaction. PMID- 22316015 TI - Prioritizing culture change in nursing homes: perspectives of residents, staff, and family members. AB - OBJECTIVES: To explore the perspectives and priorities of nursing home residents, family members, and frontline nursing staff concerning a broad range of items representing common targets of culture change initiatives. DESIGN: Qualitative study. SETTING: A Veterans Affairs Community Living Center and two community nursing homes in North Carolina. PARTICIPANTS: Residents (n = 21), family members (n = 21), and direct-care nursing staff (n = 21) were recruited, with equal numbers in each group from each site. MEASUREMENTS: Participants rated the importance of 62 items from the Centers for Medicare and Medicaid Services Artifacts of Culture Change instrument. Participants sorted cards reflecting each culture change artifact in two phases, identifying and ranking those of more and less importance to them to derive one distribution of preferences for each respondent. Q-sort analysis identified groups of respondents who prioritized similar items; qualitative analysis sought themes or explanations for the responses. RESULTS: Wide variation in respondent preferences was observed. Some respondents viewed several items that others valued highly as unimportant or undesirable. Some items were not high priorities for any respondents. Four groups of respondents with similar preferences were identified: practical and independence-focused respondents, who prioritized ease of use of the physical environment; staff-focused respondents, who prioritized nursing staff retention and development; consistency and choice-focused respondents, who prioritized stable nurse staff-resident relationships and resident choice; and activity and community-focused respondents, who prioritized community gathering spaces and activities. CONCLUSION: Resident, family, and staff priorities for culture change vary, and diverse priorities of stakeholders should be considered to inform culture change efforts on a local and national level. PMID- 22316046 TI - Service user experience of adapted dialectical behaviour therapy in a community adult mental health setting. AB - BACKGROUND: Dialectical behaviour therapy (DBT), a skill-based cognitive behavioural treatment, is increasingly used in the treatment of borderline personality disorder (BPD). AIMS: The study examined service users' perspective on the effectiveness of an adapted DBT programme, delivered within a community adult mental health setting. METHODS: Semi-structured interviews and focus groups were conducted with eight participants with a diagnosis of BPD about their experience of the programme. RESULTS: Thematic analysis focused on two key themes: evaluation of therapy and treatment impact. Therapy-specific factors and personal challenges emerged as important themes. Treatment impact raised issues relating to a renewed sense of identity and changes in daily life. CONCLUSIONS: The study describes the positive and negative experiences of service users with BPD attending an adapted DBT programme. PMID- 22316047 TI - Organization and dynamics of hippocampal membranes in a depth-dependent manner: an electron spin resonance study. AB - Organization and dynamics of neuronal membranes represent crucial determinants for the function of neuronal receptors and signal transduction. Previous work from our laboratory has established hippocampal membranes as a convenient natural source for studying neuronal receptors. In this work, we have monitored the organization and dynamics of hippocampal membranes and their modulation by cholesterol and protein content utilizing location (depth)-specific spin-labeled phospholipids by ESR spectroscopy. The choice of ESR spectroscopy is appropriate due to slow diffusion encountered in crowded environments of neuronal membranes. Analysis of ESR spectra shows that cholesterol increases hippocampal membrane order while membrane proteins increase lipid dynamics resulting in disordered membranes. These results are relevant in understanding the complex organization and dynamics of hippocampal membranes. Our results are significant in the overall context of membrane organization under low cholesterol conditions and could have implications in neuronal diseases characterized by low cholesterol conditions due to defective cholesterol metabolism. PMID- 22316048 TI - Progranulin (GP88) tumor tissue expression is associated with increased risk of recurrence in breast cancer patients diagnosed with estrogen receptor positive invasive ductal carcinoma. AB - INTRODUCTION: GP88 (progranulin) has been implicated in tumorigenesis and resistance to anti-estrogen therapies for estrogen receptor positive (ER+) breast cancer. Previous pathological studies showed that GP88 is expressed in invasive ductal carcinoma (IDC), but not in normal mammary epithelial tissue, benign lesions or lobular carcinoma. Based on these results, the present study examines GP88 prognostic significance in association with recurrence and death risks for ER+ IDC patients. METHODS: Two retrospective multi-site clinical studies examined GP88 expression by immunohistochemistry (IHC) analysis of paraffin-embedded breast tumor tissue sections from ER+ IDC patients (lymph node positive and negative, stage 1 to 3) in correlation with patients' survival outcomes. The training study established a GP88 cut-off value associated with decreased disease free (DFS) and overall (OS) survivals. The validation study verified the GP88 cut off value and compared GP88 prognostic information with other prognostic factors, particularly tumor size, grade, disease stage and lymph node status in multivariate analysis. RESULTS: GP88 expression is associated with a statistically significant increase in recurrence risk for ER+ IDC patients. The training study established that GP88 3+ score was associated with decreased DFS (P = 0.0004) and OS (P = 0.0036). The independent validation study verified that GP88 3+ score was associated with a 5.9-fold higher hazard of disease recurrence and a 2.5-fold higher mortality hazard compared to patients with tumor GP88 < 3+. GP88 remained an independent risk predictor after considering age, ethnicity, nodal status, tumor size, tumor grade, disease stage, progesterone receptor expression and treatments. CONCLUSIONS: The survival factor GP88 is a novel prognostic biomarker, predictive of recurrence risk and increased mortality for non-metastatic ER+ IDC patients. Of importance, our data show that GP88 continues to be a prognostic factor even after five years. These results also provide evidence that GP88 provides prognostic information independent of tumor and clinical characteristics and would support prospective study to examine whether GP88 expression could help stratify patients with ER+ tumors for adjuvant therapy. PMID- 22316049 TI - Good agreement of conventional and gel-based direct agglutination test in immune mediated haemolytic anaemia. AB - BACKGROUND: The aim of this study was to compare a gel-based test with the traditional direct agglutination test (DAT) for the diagnosis of immune-mediated haemolytic anaemia (IMHA). METHODS: Canine (n = 247) and feline (n = 74) blood samples were submitted for DAT testing to two laboratories. A subset of canine samples was categorized as having idiopathic IMHA, secondary IMHA, or no IMHA. RESULTS: The kappa values for agreement between the tests were in one laboratory 0.86 for canine and 0.58 for feline samples, and in the other 0.48 for canine samples. The lower agreement in the second laboratory was caused by a high number of positive canine DATs for which the gel test was negative. This group included significantly more dogs with secondary IMHA. CONCLUSIONS: The gel test might be used as a screening test for idiopathic IMHA and is less often positive in secondary IMHA than the DAT. PMID- 22316050 TI - Effect of cationic polyacrylamides on the interactions between cellulose fibers. AB - The interaction between cellulose fibers in the presence of cationic polyacrylamide (CPAM) was analyzed by rheology as a function of polyelectrolyte concentration, charge density, and molecular weight. CPAM was found to strongly influence the yield stress of cellulose suspensions; low doses of CPAM increased the yield stress, but at higher concentrations the yield stress declined. The charge density of the CPAM was the most significant factor in how yield stress responded to CPAM concentration; this effect was able to be normalized to a master curve by considering only the charged fraction of the polymer. The molecular weight of CPAM samples had some effect at high concentrations, but for lower CPAM doses the yield stress was independent of molecular weight over the range studied. The data suggest that CPAM modifies the interaction between cellulose surfaces via several mechanisms, with electrostatic interactions in the form of charge neutralization and charged patch formation dominating; polymer bridging and steric repulsion also influence the overall balance of forces between interacting cellulose fibers. PMID- 22316051 TI - Large azaacenes: pyridine rings reacting like carbonyl groups. AB - N,N'-Dihydropentaazapentacenes and -hexacenes displaying terminal pyridine rings are surprisingly easily oxidized by MnO(2) into their corresponding pyridones. PMID- 22316052 TI - Conundrums in health care reform: current experiences across the North Atlantic. AB - OBJECTIVE: To assist stakeholders (policy makers, dentists and patients) implementing the Patient Protection and Affordable Care Act of 2010 in the United States by providing information on conundrums arising from previous policies of the UK Labour government and emergent policies of the recently elected Coalition Government. METHODS: The authors provide a background to the development of National Health Service dental services contrasted with US provision. Considerations are given from the different perspectives of stakeholders involved (policy makers, dentists, and patients). CONCLUSIONS: Policy makers must work under pressure for services to remain within boundaries of finite economic resources and what people are willing to pay for. The importance is stressed that they respond to public demands and workforce capability by clearly determining what the priorities should be, what services will be delivered, and defining responsibilities. PMID- 22316053 TI - Photostability of phosphonate-derivatized, Ru(II) polypyridyl complexes on metal oxide surfaces. AB - The photostability of [Ru(II)(bpy)(2)(4,4'-(PO(3)H(2))(2)bpy)]Cl(2) (bpy = 4,4' bipyridine) on nanocrystalline TiO(2) and ZrO(2) films was investigated using a standard measurement protocol. Stability was evaluated by monitoring visible light absorbance spectral changes, in real time, during 455 nm photolysis (30 nm fwhm, 475 mW/cm(2)) in a variety of conditions relevant to dye-sensitized solar cells and dye-sensitized photoelectrosynthesis cells. Desorption (k(des)) and photochemical (k(chem)) processes were observed and found to be dependent upon solvent, anion, semiconductor, and presence of oxygen. Both processes are affected by oxygen with k(des) and k(photo) noticeably smaller in argon saturated solution. Desorption was strongly solvent and pH dependent with desorption rates increasing in the order: methanol (MeOH) ~ acetonitrile (MeCN) < propylene carbonate (PC) < pH 1 ? pH 7. Photochemistry occurred in MeOH and PC but not in aqueous, 0.1 M HClO(4) and MeCN. The anion and solvent dependence of k(photo) strongly suggests the photoreaction involves ligand substitution initiated by population of metal centered d-d states. The relative stability of -PO(3)H(2)- versus -COOH-substituted [Ru(II)(bpy)(3)](2+) was also quantitatively established. PMID- 22316054 TI - An affine micro-sphere-based constitutive model, accounting for junctional sliding, can capture F-actin network mechanics. AB - Actin filaments are a major component of the cytoskeleton and play a crucial role in cell mechanotransduction. F-actin networks can be reconstituted in vitro and their mechanical behaviour has been studied experimentally. Constitutive models that assume an idealised network structure, in combination with a non-affine network deformation, have been successful in capturing the elastic response of the network. In this study, an affine network deformation is assumed, in which we propose an alternative 3D finite strain constitutive model. The model makes use of a micro-sphere to calculate the strain energy density of the network, which is represented as a continuous distribution of filament orientations in space. By incorporating a simplified sliding mechanism at the filament-to-filament junctions, premature filament locking, inherent to affine network deformation, could be avoided. The model could successfully fit experimental shear data for a specific cross-linked F-actin network, demonstrating the potential of the novel model. PMID- 22316055 TI - Low temperature-fired Ni-Cu-Zn ferrite nanoparticles through auto-combustion method for multilayer chip inductor applications. AB - Ferrite nanoparticles of basic composition Ni0.7-xZnxCu0.3Fe2O4 (0.0 <= x <= 0.2, x = 0.05) were synthesized through auto-combustion method and were characterized for structural properties using X-ray diffraction [XRD], scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy [FT-IR]. XRD analysis of the powder samples sintered at 600 degrees C for 4 h showed the cubic spinel structure for ferrites with a narrow size distribution from 28 to 32 nm. FT-IR showed two absorption bands (v1 and v2) that are attributed to the stretching vibration of tetrahedral and octahedral sites. The effect of Zn doping on the electrical properties was studied using dielectric and impedance spectroscopy at room temperature. The dielectric parameters (epsilon', epsilon", tandelta, and sigmaac) show their maximum value for 10% Zn doping. The dielectric constant and loss tangent decrease with increasing frequency of the applied field. The results are explained in the light of dielectric polarization which is similar to the conduction phenomenon. The complex impedance shows that the conduction process in grown nanoparticles takes place predominantly through grain boundary volume.PACS: 75.50.Gg; 78.20; 77.22.Gm. PMID- 22316056 TI - Canine bone marrow mesenchymal stromal cells with lentiviral mHCN4 gene transfer create cardiac pacemakers. AB - BACKGROUND AIMS: The study objective was to test the ability of canine mesenchymal stromal cells (cMSC) transfected with the mouse hyperpolarization activated cyclic nucleotide-gated channel 4 (mHCN4) gene to deliver a biologic pacemaker to the canine heart. METHODS AND RESULTS: cMSC that were transfected by lentiviral vector with the cardiac pacemaker gene mHCN4 expressed high levels of Cs(+) -sensitive current (26.4 +/- 1.8pA/pF at -140 mV; (n = 17) and were activated in the diastolic potential range with a reversal potential of -29.7 +/- 2.5 mV (n = 14), confirming that the expressed current was Funny current (I(f)) like. Next, 3 * 10(6) cMSC transfected with either control plasmid or the mHCN4 gene construct were injected subepicardially into the canine right ventricular wall in situ. During sinus arrest, all control hearts had spontaneous atrioventricular node rhythms [rate = 21 +/- 5 beats per minute (b.p.m.)]. In the mHCN4 group, six of eight animals developed spontaneous ventricular rhythms of right-sided origin (rate = 45 +/- 9b.p.m.; P < 0.01). Moreover, immunohistochemical analysis of the injected regions demonstrated neither apoptosis nor cellular or humoral rejection at 2 weeks. CONCLUSIONS: These results demonstrate that genetically modified cMSC can express functional HCN4 channels in vitro and in vivo and represent a novel delivery system for pacemaker genes into the heart. PMID- 22316057 TI - The effect of a mild base on curcumin in methanol and ethanol. AB - Steady-state and time-resolved emission techniques were employed to study the effect of acetate, a mild base, on the luminescence of curcumin in methanol and ethanol. We found that the steady-state emission intensity as well as the average fluorescence decay time are reduced by a factor of 5 when the acetate concentration is raised to about 1.8 M. We attribute this large effect to an excited-state proton transfer (ESPT) from the acidic groups of curcumin to the acetate anion. We analyze the experimental data in terms of an ESPT reaction occurring between a photoacid and a base. PMID- 22316059 TI - Mobility of cesium through the Callovo-Oxfordian claystones under partially saturated conditions. AB - The diffusion of cesium was studied in an unsaturated core of Callovo-Oxfordian claystone, which is a potential host rock for retrievable disposal of high-level radioactive wastes. In-diffusion laboratory experiments were performed on rock samples with water saturation degrees ranging from 81% to 100%. The analysis of both cesium concentration monitoring in the source reservoir and post-mortem cesium rock concentration profile of the samples was carried out using a chemical transport code where the sorption of cesium was described by a multisite ion exchange model. The results showed that cesium exhibited a clear trend related to the saturation degree of the sample. The more dehydrated the rock sample, the slower the decrease of cesium concentration, and the thinner the penetration depth of cesium was. The effective diffusion coefficient (De) for cesium decreased from 18.5 * 10(-11) m(2) s(-1) at full-saturation to 0.3 * 10(-11) m(2) s(-1) for the more dehydrated sample. This decrease is almost 1 order of magnitude higher than that for tritiated water (HTO), although a similar behavior could have been expected, since cesium is known to diffuse in the same parts of the pore space as HTO in fully saturated claystones. PMID- 22316060 TI - The deviated balance between regulatory T cell and Th17 in autoimmunity. AB - Identifying the regulatory T cells (Tregs) and Th17 cells led to breaking the dichotomy of Th1/Th2 cells axis in immune responses involved in several autoimmune diseases. It is now well known that Tregs and Th17 cells are main orchestra leaders in pathogenesis symphony of autoimmunity. While Tregs are protective cells in autoimmune diseases, Th17 cells enhance the progression of autoimmune responses through induction of various pro-inflammatory reactions. It seems that the progression of autoimmunity may be associated with increase in Th17 and decrease in Treg levels, so that skewed balance between Tregs and Th17 toward Th17 is a phenomenon, which could be observed during progression of several autoimmune diseases. Although it is suggested that expansion and transfer of Tregs can be a new therapeutic target for autoimmune diseases, however, recent data about the phenotype conversion of Tregs into Th17 cells obligate us to more investigation on this approaching. Thus, identifying the new factors that induce stable phenotype in Tregs and prevent their phenotype conversion into Th17 cells as well as targeting the factor, which can modulate their balance, might be recommended as a new promising therapeutic method for autoimmune therapy. In this review, we try to clarify the factors, which can affect on this balance in various autoimmune diseases, as new targets in treatment of these diseases. PMID- 22316061 TI - S-alkylation of thiacalixarenes: how the regio- and stereoselectivities depend on the starting conformation. AB - S-alkylation of all four thiacalix[4]arene conformations was accomplished using alkyl triflates. The corresponding sulfonium salts are formed in a highly regio- and stereoselective manner depending on the conformation used. Interestingly, only mono- or disubstituted sulfonium salts can be prepared. Although many regio- and stereoisomers are theoretically possible, only one dialkylated cone and 1,2 alternate derivatives were formed, while only a single isomer of monoalkylated partial cone and 1,3-alternate were isolated. The combination of experimental results with the quantum-chemical approach using the B3LYP/6-311G(d,p) method resulted in the elucidation of the rules governing the regio- and stereochemical outcomes of the alkylation reactions. All S-alkylated compounds represent a novel type of substitution pattern in calixarene chemistry showing the wide-ranging possibility of thiacalixarene skeleton modifications. PMID- 22316062 TI - Plasma testosterone in adult normoglycaemic men: impact of hyperinsulinaemia. AB - This study analysed the relationship of plasma testosterone with beta-cell secretion, insulin sensitivity and other pituitary-target gland hormones in normoglycaemic adult men. The sample frame was the 'Offspring of individuals with diabetes study' database. A total of 358 offspring of individuals with type-2 diabetes (T2DM) and 287 individuals without known family history of T2DM were recruited for the study. Normoglycaemic men aged >=18 years (maximum 55) were selected for this analysis. All participants underwent 75 g oral glucose tolerance test (OGTT); blood samples were collected at 0, 30, 60 and 120 min for plasma insulin and C-peptide. Total testosterone, cortisol, adrenocorticotropic hormone, thyroid stimulating hormone and thyroxine (T4) were measured in the fasting sample. A total of 164 men (age 28 +/- 7.7 years) were included in analysis. Testosterone correlated negatively with BMI, waist to hip ratio (WHR), area under curve (AUC) of C-peptide and insulin (during OGTT) and was positively correlated with insulin sensitivity (r ~ 0.4). Cortisol and T4 positively correlated (weak) with testosterone (r ~ 0.2). In multivariate analysis, AUC C peptide, BMI, WHR (negatively) and cortisol (positively) were related to testosterone. Concluding, testosterone correlated negatively with BMI and beta cell secretion. There was a positive association of testosterone with insulin sensitivity, cortisol and T4. PMID- 22316064 TI - Mechanical pain sensitivity of deep tissues in children--possible development of myofascial trigger points in children. AB - BACKGROUND: It is still unclear when latent myofascial trigger points (MTrPs) develop during early life. This study is designed to investigate the mechanical pain sensitivity of deep tissues in children in order to see the possible timing of the development of latent MTrPs and attachment trigger points (A-TrPs) in school children. METHODS: Five hundreds and five healthy school children (age 4- 11 years) were investigated. A pressure algometer was used to measure the pressure pain threshold (PPT) at three different sites in the brachioradialis muscle: the lateral epicondyle at elbow (site A, assumed to be the A-TrP site), the mid-point of the muscle belly (site B, assumed to be the MTrP site), and the muscle-tendon junction as a control site (site C). RESULTS: The results showed that, for all children in this study, the mean PPT values was significantly lower (p < 0.05) at the assumed A-TrP site (site A) than at the other two sites, and was significantly lower (p < 0.05) at the assumed MTrP site (site B) than at the control site (site C). These findings are consistent if the data is analyzed for different genders, different dominant sides, and different activity levels. CONCLUSIONS: It is concluded that a child had increased sensitivity at the tendon attachment site and the muscle belly (endplate zone) after age of 4 years. Therefore, it is likely that a child may develop an A-Trp and a latent MTrP at the brachioradialis muscle after the age of 4 years. The changes in sensitivity, or the development for these trigger points, may not be related to the activity level of children aged 7-11 years. Further investigation is still required to identify the exact timing of the initial occurrence of a-Trps and latent MTrPs. PMID- 22316065 TI - Cell-mediated and humoral immune responses in pigs following primary and challenge-exposure to Lawsonia intracellularis. AB - To investigate immune responses upon re-infection with Lawsonia intracellularis, local and peripheral humoral and cell-mediated immune responses to primary and challenge inoculations were studied in 22 pigs. Pigs were orally inoculated with virulent L. intracellularis at the age of 5-6 weeks, treated with antibiotics and challenged with a re-inoculation (RE) at the age of 12 weeks. Treatment control (TC) pigs received only the primary inoculation and challenge control (CC) pigs received only the secondary inoculation at 12 weeks of age. Following this regimen, all RE pigs were protected against the re-infection as defined by reduced colonisation and pathology of intestinal mucosa, absence of bacterial shedding and without increase in serum acute phase protein response. In the protected RE pigs, serum IgG responses were variable with both high and low responders. Serum IgA responses were not boosted by the re-inoculation, since identical intestinal IgA responses developed in response to the inoculation in both the susceptible CC pigs and the protected RE pigs. A memory recall cell mediated immune response developed in RE pigs which was significantly stronger compared to the primary response in age-matched CC pigs as assessed by whole blood IFN-gamma assay and by calculation of IFN-gamma integrated median fluorescence intensity (iMFI) after flow cytometry. The major IFN-gamma producing cells were identified as CD8+ and CD4+CD8+ double positive lymphocytes. The results indicate that cell-mediated immune responses are likely mediators of protective immunity against L. intracellularis, with CD8+ effector cells and CD4+CD8+ double positive memory T cells as main contributors to the antigen specific IFN-gamma production. PMID- 22316066 TI - Comparative characteristics of membrane-active single-chained ether phospholipids: PAF and lyso-PAF in Langmuir monolayers. AB - 1-O-Octadecyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) and its deacetylated precursor (lyso-PAF) are membrane-active single-chained ether phospholipids, which play an important signaling role in different physiological processes. There is strong evidence that one of the possible mechanisms of PAF and lyso-PAF activity is connected with their direct influence on biomembranes. Although both lipids have very similar structure, their biological activity is very different and in some cases even antagonistic. Unfortunately, there is a lack of the studies correlating these observations with the molecular structure of both compounds. Therefore, we decided to apply model systems and advanced physicochemical methods to explore this subject and look for the reasons of the observed discrepancies. As a model system, we prepared Langmuir monolayers of PAF and lyso-PAF at the air/water interface. The physicochemical characteristic of the model membranes under different experimental conditions was performed with the application of the Langmuir monolayer technique, Brewster angle microscopy, and the methods based on synchrotron radiation scattering (XR and GIXD). Both compounds form stable Langmuir monolayers, in which the lipid molecules are strongly immersed into the water subphase. The monolayers have expanded character, meaning that the hydrophobic tails are considerably tilted and disordered. Similarly to biochemical studies, also in our model systems, profound differences in the properties of PAF and lyso-PAF were observed. Contrary to PAF, the lyso-PAF molecules express the propensity to form organized, periodical structures in the model membranes. It is manifested in the phase transition observed in the course of the lyso-PAF pi-A isotherm which was correlated with the diffraction signal registered with the application of the GIXD method. The formation of 2D domains of hexagonal ordering of the film forming molecules was observed only for the lyso precursor. The observed differences between PAF and lyso-PAF were explained taking into consideration the chemical activity of the free hydroxyl group present in the headgroup of the latter molecule. The formation of hydrogen bonds between the lyso-PAF molecules as well as the stronger hydration of its hydrophilic fragment can be the key factor differentiating the activity of PAF and lyso-PAF in the investigated systems as well as in the native biomembranes. PMID- 22316067 TI - Postoperative spondylodiscitis following transforaminal percutaneous endoscopic lumbar discectomy: clinical characteristics and preventive strategies. AB - INTRODUCTION: We aimed to demonstrate the unique clinical characteristics and outcomes of spondylodiscitis after transforaminal percutaneous endoscopic lumbar discectomy (PELD), and we also discuss about adequate preventive methods of this unexpected complication. METHODS: The medical records of 9821 consecutive cases treated with PELD between January 2001 and December 2009 were reviewed. All cases of postoperative infection were identified. The clinical course, infection type, laboratory results and treatment options for each case were available from their records. RESULTS: Of the 9821 patients, 12 (0.12%) were identified as having postoperative infections, and in all these cases, the infection manifested as spondylodiscitis. Four patients were treated with only antibiotic therapy; two patients were treated with surgical debridement; and the remaining six patients who were unresponsive to the initial therapies finally required lumbar interbody fusion with posterior instrumentation surgery. The mean Oswestry Disability Index (ODI) improved from 60.4% +/- 19.4% to 29.3% +/- 15.4%. Based on the modified MacNab criteria, 7 of the 12 patients (58.3%) showed an excellent or good outcome. CONCLUSION: Postoperative spondylodiscitis following PELD is relatively rare. However, its clinical progression could be more rapid and more serious than that after open surgery. Therefore, thorough preventive strategies for postoperative spondylodiscitis are mandatory. PMID- 22316068 TI - Clinical coding of pituitary operations. PMID- 22316069 TI - A novel entry to functionalized benzofurans and indoles via palladium(0) catalyzed arylative dearomatization of furans. AB - A novel entry to functionalized benzofurans and indoles from furans in moderate to good yields has been developed. This protocol involves palladium(0)-catalyzed dearomatizing intramolecular arylation of the furan ring, formation of a pi allylic palladium complex, furan ring opening, and a beta-hydride elimination sequence. PMID- 22316070 TI - Predictors of treatment with osteoporosis medications after recent fragility fractures in a multinational cohort of postmenopausal women. AB - OBJECTIVES: To determine the proportion of untreated women who reported receiving treatment after incident fracture and to identify factors that predict treatment across an international spectrum of individuals. DESIGN: Prospective observational study. Self-administered questionnaires were mailed at baseline and 1 year. SETTING: Multinational cohort of noninstitutionalized women recruited from 723 primary physician practices in 10 countries. PARTICIPANTS: Sixty thousand three hundred ninety-three postmenopausal women aged 55 and older were recruited with a 2:1 oversampling of women aged 65 and older. MEASUREMENTS: Data collected included participant demographics, medical history, fracture occurrence, medications, and risk factors for fracture. Anti-osteoporosis medications (AOMs) included estrogen, selective estrogen receptor modulators, bisphosphonates, calcitonin, parathyroid hormone, and strontium. RESULTS: After the first year of follow-up, 1,075 women reported an incident fracture. Of these, 17% had started AOM, including 15% of those with a single fracture and 35% with multiple fractures. Predictors of treatment included baseline calcium use (P = .01), baseline diagnosis of osteoporosis (P < .001), and fracture type (P < .001). In multivariable analysis, women taking calcium supplements at baseline (odds ratio (OR) = 1.67) and with a baseline diagnosis of osteoporosis (OR = 2.55) were more likely to be taking AOM. Hip fracture (OR = 2.61), spine fracture (OR = 6.61), and multiple fractures (OR = 3.79) were associated with AOM treatment. Age, global region, and use of high-risk medications were not associated with treatment. CONCLUSION: More than 80% of older women with new fractures were not treated, despite the availability of AOM. Important factors associated with treatment in this international cohort included diagnosis of osteoporosis before the incident fracture, spine fracture, and to a lesser degree, hip fracture. PMID- 22316071 TI - Blood compatibility of iron-doped nanosize hydroxyapatite and its drug release. AB - Nanosize hydroxyapatite (nHAp) doped with varying levels of Fe(3+) (Fe-nHAp of average size 75 nm) was synthesized by hydrothermal and microwave techniques. The samples were characterized for physiochemical properties by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), inductively coupled plasma optical emission spectrometer (ICP-OES), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), mechanical and dielectric properties. The biological properties like hemocompatibility, antibacterial efficacy, in vitro bioactivity and the cell proliferation of the samples were determined. XRD pattern of the samples were of single phase hydroxyapatite. As the content of Fe(3+) increased, the crystallite size as well as crystallinity decreased along with a morphological change from spherulites to rods. The dielectric constants and Vickers hardness were enhanced on Fe(3+) doping. The VSM studies revealed that the saturation magnetization (M(s)) and retentivity (M(r)) were found to increase for Fe-nHAp. nHAp impregnated with an antibiotic as a new system for drug delivery in the treatment of chronic osteomyelitis was also attempted. The in vitro drug release with an antibiotic amoxicillin and anticancer drug 5 fluorouracil showed sustained release for the lowest concentration of Fe(3+), while with an increase in the content; there was a rapid release of the drug. The hemolytic assay of Fe(3+) doped samples revealed high blood compatibility (<5% hemolysis). The antibacterial activities of the antibiotic impregnated materials were tested against a culture of E. coli, S. epidermidis and S. aureus by agar diffusion test. The in vitro bioactivity test using simulated body fluid (SBF) showed better bone bonding ability by the formation of an apatite layer on the doped samples. The growth of the apatite layer on the samples surface has been confirmed by EDS analysis. The proliferative potential of MG63 cells by MTT assay confirmed the noncytotoxicity of the samples. PMID- 22316072 TI - The first nosocomial outbreak of methicillin-resistant Staphylococcus aureus in horses in Sweden. AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) in animals is a rare finding in Sweden. In horses, MRSA was first detected in a screening survey in 2007. In 2008, six clinical cases occurred in an equine hospital, indicating an outbreak. METHOD: All MRSA isolates detected, 11 spa-type t011 and one t064 (n = 12), in infected horses (n = 10) and screening of horses (n = 2) in Sweden from December 2007 to March 2010 were retrospectively analysed with pulsed-field gel electrophoresis (PFGE) using Cfr9I and ApaI restriction enzymes, to study relationship between the isolates. Medical records of infected horses and outbreak investigation notes were scrutinised to monitor the clinical outcome and other aspects of the outbreak. RESULTS: Eight of the 10 infected horses were linked to one equine hospital and two to another hospital in the same region. The six horses infected with MRSA in 2008 underwent surgery during the period 22 May 7 July in one of the hospitals. Four more infections linked to the two hospitals were notified between 2009 and March 2010.Nine of the 11 spa-type t011 isolates had identical Cfr9I and ApaI PFGE pattern. All six infected horses from 2008 presented with this MRSA. Two t011 isolates differed in one and two bands, respectively, in PFGE.Nine horses suffered from surgical site infections (SSI). No antimicrobials were used following the MRSA diagnosis and the infections cleared. The time from surgery to MRSA diagnosis differed greatly between the horses (range 15-52 days). CONCLUSIONS: Association in time and space of six horses infected with an identical MRSA strain of spa-type t011 confirmed an outbreak. Two isolates found in 2009 and 2010 in the outbreak hospital were closely related to the outbreak strain, indicating one circulating strain. Both spa-type t011 and t064 have been reported in horses in Europe prior to these findings. The observation that the infections cleared although antimicrobials were not used is encouraging for future prudent use of antimicrobials. The time from surgery to bacteriological diagnosis was not acceptable in most cases, as contagious spread was a risk. Sampling when symptoms of infection are noticed and accurate analysis are thus important. PMID- 22316073 TI - Zinc adjunct therapy reduces case fatality in severe childhood pneumonia: a randomized double blind placebo-controlled trial. AB - BACKGROUND: Pneumonia is a leading cause of children's deaths in developing countries and hinders achievement of the fourth Millennium Development Goal. This goal aims to reduce the under-five mortality rate, by two thirds, between 1990 and 2015.Few studies have examined the impact of zinc adjunct therapy on the outcome of childhood pneumonia. We determined the effect of zinc as adjunct therapy on time to normalization of respiratory rate, temperature and oxygen saturation. We also studied the effect of zinc adjunct therapy on case fatality of severe childhood pneumonia (as a secondary outcome) in Mulago Hospital, Uganda. METHODS: In this double blind, randomized, placebo-controlled clinical trial, 352 children aged 6 to 59 months, with severe pneumonia were randomized to zinc (20 mg for children >= 12 months, and 10 mg for those < 12 months) or a placebo once daily for seven days, in addition to standard antibiotics for severe pneumonia. Children were assessed every six hours. Oxygen saturation was normal if it was above 92% (breathing room air) for more than 15 minutes. The respiratory rate was normal if it was consistently (more than 24 hours) below 50 breaths per minute in infants and 40 breaths per minute in children above 12 months of age. Temperature was normal if consistently below 37.5 degrees C. The difference in case fatality was expressed by the risk ratio between the two groups. RESULTS: Time to normalization of the respiratory rate, temperature and oxygen saturation was not significantly different between the two arms.Case fatality was 7/176 (4.0%) in the zinc group and 21/176 (11.9%) in the placebo group: Relative Risk 0.33 (95% CI 0.15 to 0.76). Relative Risk Reduction was 0.67 (95% CI 0.24 to 0.85), while the number needed to treat was 13. Among HIV infected children, case fatality was higher in the placebo (7/27) than in the zinc (0/28) group; RR 0.1 (95% CI 0.0, 1.0).Among 127 HIV uninfected children receiving the placebo, case fatality was 7/127 (5.5%); versus 5/129 (3.9%) among HIV uninfected group receiving zinc: RR 0.7 (95% CI 0.2, 2.2). The excess risk of death attributable to the placebo arm (Absolute Risk Reduction or ARR) was 8/100 (95% CI: 2/100, 14/100) children. This excess risk was substantially greater among HIV positive children than in HIV negative children (ARR: 26 (95% CI: 9, 42) per 100 versus 2 (95% CI: -4, 7) per 100); P-value for homogeneity of risk differences = 0.006. CONCLUSION: Zinc adjunct therapy for severe pneumonia had no significant effect on time to normalization of the respiratory rate, temperature and oxygen saturation. However, zinc supplementation in these children significantly decreased case fatality.The difference in case fatality attributable to the protective effect of zinc therapy was greater among HIV infected than HIV uninfected children. Given these results, zinc could be considered for use as adjunct therapy for severe pneumonia, especially among Highly Active Antiretroviral Therapynaive HIV infected children in our environment. CLINICAL TRIALS REGISTRATION NUMBER: clinicaltrials.gov NCT00373100. PMID- 22316074 TI - Molecular spectroscopy evidence of berberine binding to DNA: comparative binding and thermodynamic profile of intercalation. AB - Berberine (BH) is an important traditional medicinal herb endowed with diverse pharmacological and biological activities. In this work, the binding characteristics and molecular mechanism of the interaction between the BH and herring sperm DNA were explored by UV-vis absorbance and fluorescence spectroscopy. In the mechanism discussion, fluorescence quenching, absorption spectra, competition experiment, and iodide quenching experiment studies hinted at an intercalative mode of binding for BH to DNA. Fluorescence studies revealed the binding constant (K) of BH-DNA was ~10(4) L.mol(-1). The effects of temperature, chemical denaturants, thermal denaturation, and pH were studied to show the factors of the interaction and provided further support for the intercalative binding mode. The results of thermodynamic parameters DeltaG, DeltaH, and DeltaS at different temperatures indicated that the hydrogen bonds and van der Waals interactions played major roles in the reaction, and the effect of ionic strength indicated that electrostatic attraction between the BH and DNA was also a component of the interaction. PMID- 22316075 TI - PPISEARCHENGINE: gene ontology-based search for protein-protein interactions. AB - This paper presents a new search engine called PPISearchEngine which finds protein-protein interactions (PPIs) using the gene ontology (GO) and the biological relations of proteins. For efficient retrieval of PPIs, each GO term is assigned a prime number and the relation between the terms is represented by the product of prime numbers. This representation is hidden from users but facilitates the search for the interactions of a query protein by unique prime factorisation of the number that represents the query protein. For a query protein, PPISearchEngine considers not only the GO term associated with the query protein but also the GO terms at the lower level than the GO term in the GO hierarchy, and finds all the interactions of the query protein which satisfy the search condition. In contrast, the standard keyword-matching or ID-matching search method cannot find the interactions of a protein unless the interactions involve a protein with explicit annotations. To the best of our knowledge, this search engine is the first method that can process queries like 'for protein p with GO [Formula: see text], find p's interaction partners with GO [Formula: see text]'. PPISearchEngine is freely available to academics at http://search.hpid.org/. PMID- 22316076 TI - Energetics and structural properties, in the gas phase, of trans-hydroxycinnamic acids. AB - We have studied the energetics and structural properties of trans-cinnamic acid (CA), o-, m-, and p-coumaric acids (2-, 3-, and 4-hydroxycinnamic acids), caffeic acid (3,4-dihydroxycinnamic acid), ferulic acid (4-hydroxy-3-methoxycinnamic acid), iso-ferulic acid (3-hydroxy-4-methoxycinnamic acid), and sinapic acid (3,5 dimethoxy-4-hydroxycinnamic acid). The experimental values of Delta(f)H(m) degrees (g), determined (in kJ.mol(-1)) for CA (-229.8 +/- 1.9), p-coumaric acid (-408.0 +/- 4.4), caffeic acid (-580.0 +/- 5.9), and ferulic acid (-566.4 +/- 5.7), allowed us to derive Delta(f)H(m) degrees (g) of o-coumaric acid (-405.6 +/ 4.4), m-coumaric acid (-406.4 +/- 4.4), iso-ferulic acid (-565.2 +/- 5.7), and sinapic acid (-698.8 +/- 4.1). From these values and by use of isodesmic/homodesmotic reactions, we studied the energetic effects of pi-donor substituents (-OH and -OCH(3)) in cinnamic acid derivatives and in the respective benzene analogues. Our results indicate that the interaction between -OCH(3) and/or -OH groups in hydroxycinnamic acids takes place without significant influence of the propenoic fragment. PMID- 22316077 TI - An exploratory study into whether self-monitoring improves adherence to daily flossing among dental patients. AB - OBJECTIVES: This exploratory study evaluated the effectiveness of an action control behavioral intervention on adherence to dental flossing in patients with periodontal disease. Action control, that is, monitoring one's behavior and evaluating it against a self-set standard, has been suggested as a self regulatory strategy that can assist people who intend to engage in behavioral change. METHODS: In a single-center, single-blind prospective trial, 73 dental patients received a behavioral intervention, which was either matched or mismatched to their stage of behavioral change. Through responses to a standardized self-report measure, participants were classified either as motivational (i.e., not ready to change) or volitional (i.e., contemplating change) with regard to dental flossing. The intervention consisted of a simple self-monitoring tool for dental flossing in the form of a diary. Flossing frequency, dental plaque, and bleeding scores were measured before and at 4 weeks postintervention. RESULTS: Flossing frequency, dental plaque, and bleeding scores improved (P < 0.001) in both stage-matched and stage-mismatched patients. CONCLUSIONS: A brief behavioral intervention enhances adherence to dental flossing, regardless of participants' stage of change. Keeping a flossing diary can increase dental flossing and reduce plaque and bleeding scores in patients with periodontal disease, in the short term. PMID- 22316078 TI - Clinical review: humidifiers during non-invasive ventilation--key topics and practical implications. AB - Inadequate gas conditioning during non-invasive ventilation (NIV) can impair the anatomy and function of nasal mucosa. The resulting symptoms may have a negative effect on patients' adherence to ventilatory treatment, especially for chronic use. Several parameters, mostly technical aspects of NIV, contribute to inefficient gas conditioning. Factors affecting airway humidity during NIV include inspiratory flow, inspiratory oxygen fraction, leaks, type of ventilator, interface used to deliver NIV, temperature and pressure of inhaled gas, and type of humidifier. The correct application of a humidification system may avoid the effects of NIV-induced drying of the airway. This brief review analyses the consequences of airway dryness in patients receiving NIV and the technical tools necessary to guarantee adequate gas conditioning during ventilatory treatment. Open questions remain about the timing of gas conditioning for acute or chronic settings, the choice and type of humidification device, the interaction between the humidifier and the underlying disease, and the effects of individual humidification systems on delivered humidity. PMID- 22316079 TI - Brazilian propolis inhibits the differentiation of Th17 cells by inhibition of interleukin-6-induced phosphorylation of signal transducer and activator of transcription 3. AB - Propolis is a resinous substance collected by honeybees from leaf buds and cracks in the bark of various plants. It has been reported to show immunomodulatory activity. Previously, we reported the protective effect of Brazilian propolis ethanolic extract against the pathogenesis of collagen-induced arthritis (CIA), an experimental animal model of rheumatoid arthritis (RA). Moreover, we found that the protective effect against CIA was involved in suppression of the production of interleukin-17 (IL-17) in CIA mice. In the present study, we demonstrated for the first time that propolis inhibited IL-6 plus transforming growth factor-beta induced Th17 differentiation in vitro. Propolis also suppressed the IL-6-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3), a cytokine-activated essential transcription factor in Th17 development, concomitantly with the enhanced suppressor of cytokine signaling 3 expression involved in the downregulation of STAT3 phosphorylation. These data suggest that the suppressive effect of propolis on Th17 differentiation might be useful for controlling unbalanced cytokine networks in autoimmune diseases. PMID- 22316080 TI - Humic acid facilitates the transport of ARS-labeled hydroxyapatite nanoparticles in iron oxyhydroxide-coated sand. AB - Hydroxyapatite nanoparticles (nHAP) have been widely used to remediate soil and wastewater contaminated with metals and radionuclides. However, our understanding of nHAP transport and fate is limited in natural environments that exhibit significant variability in solid and solution chemistry. The transport and retention kinetics of Alizarin red S (ARS)-labeled nHAP were investigated in water-saturated packed columns that encompassed a range of humic acid concentrations (HA, 0-10 mg L(-1)), fractional surface coverage of iron oxyhydroxide coatings on sand grains (lambda, 0-0.75), and pH (6.0-10.5). HA was found to have a marked effect on the electrokinetic properties of ARS-nHAP, and on the transport and retention of ARS-nHAP in granular media. The transport of ARS-nHAP was found to increase with increasing HA concentration because of enhanced colloidal stability and the reduced aggregate size. When HA = 10 mg L( 1), greater ARS-nHAP attachment occurred with increasing lambda because of increased electrostatic attraction between negatively charged nanoparticles and positively charged iron oxyhydroxides, although alkaline conditions (pH 8.0 and 10.5) reversed the surface charge of the iron oxyhydroxides and therefore decreased deposition. The retention profiles of ARS-nHAP exhibited a hyperexponential shape for all test conditions, suggesting some unfavorable attachment conditions. Retarded breakthrough curves occurred in sands with iron oxyhydroxide coatings because of time-dependent occupation of favorable deposition sites. Consideration of the above effects is necessary to improve remediation efficiency of nHAP for metals and actinides in soils and subsurface environments. PMID- 22316082 TI - What can we learn from ionic conductivity measurements in polymer electrolytes? A case study on poly(ethylene oxide) (PEO)-NaI and PEO-LiTFSI. AB - We explore in detail what information on ionic diffusivity and ion pairing can be exclusively gained from combining accurate direct-current conductivity data in polymer electrolytes with a novel evaluation model. The study was performed on two prototype systems based on poly(ethylene oxide) (PEO) with known disparate ion-association properties, which are due to the dissimilar salt components being either sodium iodide (NaI) or lithium bis(trifluoromethane-sulfonyl)imide (LiN(CF(3)SO(2))(2) or LiTFSI). The temperature dependence of the conductivity can be described by an extended Vogel-Tammann-Fulcher (VTF) equation, which involves a Boltzmann factor containing the pair-formation enthalpy DeltaH(p). We find a distinct increase of the positive DeltaH(p) values with decreasing salt concentration and similarly clear trends for the pertinent VTF parameters. The analysis further reveals that PEO-NaI combines a high pair fraction with a high diffusivity of the I(-) ion. By contrast, PEO-LiTFSI appears to be characterized by a low ion-pairing tendency and a relatively low mobility of the bulky TFSI(-) ion. The observed marked differences between PEO-NaI and PEO-LiTFSI complexes of homologous composition are most pronounced at high temperatures and low salt concentrations. PMID- 22316083 TI - Child and family health nurses' experiences of oral health of preschool children: a qualitative approach. AB - OBJECTIVES: The objective of this study was to explore Child and Family Health Nurses' work-related experiences of dental disease in young children. METHODS: Child and Family Health Nurses (n = 21) who recruited new mothers to an ongoing birth cohort study that began in South Western Sydney, Australia were invited to take part in a qualitative study. A semi-structured, in-depth interview technique was used to explore their experiences of preschool child oral health and how this affects their working lives. Interviews were audio-recorded, transcribed verbatim, and analyzed using a thematic analysis. RESULTS: The nurses considered dental caries to be a significant health issue for young children and their families. They thought that the burden of dental disease in preschool children was underestimated in disadvantaged and multicultural populations. In addition, they reported that parents were often unaware of the disease process and were ignorant of the relationship between bottle feeding and dental caries. Once the parents were informed about their child's poor oral health, they had feelings of anger, despair, and guilt. CONCLUSIONS: This study highlights that oral health problems are a significant segment of the child health problems identified by nurses in their daily work. The nurses perceived the problem of dental caries to be one of a lack of parental knowledge, and families should be educated not only on "what" but also on "how" to feed their children. The primary healthcare team should work collaboratively to educate families in a culturally appropriate way. PMID- 22316084 TI - Investigation of first ray mobility during gait by kinematic fluoroscopic imaging -a novel method. AB - BACKGROUND: It is often suggested that sagittal instability at the first tarso metatarsal joint level is a primary factor for hallux valgus and that sagittal instability increases with the progression of the deformity. The assessment of the degree of vertical instability is usually made by clinical evaluation while any measurements mostly refer to a static assessment of medial ray mobility (i.e. the plantar/dorsal flexion in the sagittal plane). Testing methods currently available cannot attribute the degree of mobility to the corresponding anatomical joints making up the medial column of the foot. The aim of this study was to develop a technique which allows for a quantification of the in-vivo sagittal mobility of the joints of the medial foot column during the roll-over process under full weight bearing. METHODS: Mobility of first ray bones was investigated by dynamic distortion-free fluoroscopy (25 frames/s) of 14 healthy volunteers and 8 patients with manifested clinical instability of the first ray. A CAD-based evaluation method allowed the determination of mobility and relative displacements and rotations of the first ray bones within the sagittal plane during the stance phase of gait. RESULTS: Total flexion of the first ray was found to be 13.63 (SD 6.14) mm with the healthy volunteers and 13.06 (SD 8.01) mm with the patients (resolution: 0.245 mm/pixel). The dorsiflexion angle was 5.27 (SD 2.34) degrees in the healthy volunteers and increased to 5.56 (SD 3.37) degrees in the patients. Maximum rotations were found at the naviculo-cuneiform joints and least at the first tarso-metatarsal joint level in both groups. CONCLUSIONS: Dynamic fluoroscopic assessment has been shown to be a valuable tool for characterisation of the kinematics of the joints of the medial foot column during gait.A significant difference in first ray flexion and angular rotation between the patients and healthy volunteers however could not be found. PMID- 22316085 TI - Synthesis of functionalized indolizines via copper-catalyzed annulation of 2 alkylazaarenes with alpha,beta-unsaturated carboxylic acids. AB - A novel copper-catalyzed annulation of 2-alkylazaarenes with alpha,beta unsaturated carboxylic acids has been accomplished. This reaction featuring C-H olefination and decarboxylative amination processes provides a concise access to C-2 arylated indolizines from simple and readily available starting materials. PMID- 22316086 TI - Lipid raft/caveolae signaling is required for Cryptococcus neoformans invasion into human brain microvascular endothelial cells. AB - BACKGROUND: Cryptococcus neoformans has a predilection for central nervous system infection. C. neoformans traversal of the blood brain barrier, composed of human brain microvascular endothelial cells (HBMEC), is the crucial step in brain infection. However, the molecular mechanism of the interaction between Cryptococcus neoformans and HBMEC, relevant to its brain invasion, is still largely unknown. METHODS: In this report, we explored several cellular and molecular events involving the membrane lipid rafts and caveolin-1 (Cav1) of HBMEC during C. neoformans infection. Immunofluorescence microscopy was used to examine the roles of Cav1. The knockdown of Cav1 by the siRNA treatment was performed. Phosphorylation of Cav1 relevant to its invasion functions was investigated. RESULTS: We found that the host receptor CD44 colocalized with Cav1 on the plasma membrane, and knockdown of Cav1 significantly reduced the fungal ability to invade HBMEC. Although the CD44 molecules were still present, HBMEC membrane organization was distorted by Cav1 knockdown. Concomitantly, knockdown of Cav1 significantly reduced the fungal crossing of the HBMEC monolayer in vitro. Upon C. neoformans engagement, host Cav1 was phosphorylated in a CD44 dependent manner. This phosphorylation was diminished by filipin, a disrupter of lipid raft structure. Furthermore, the phosphorylated Cav1 at the lipid raft migrated inward to the perinuclear localization. Interestingly, the phospho-Cav1 formed a thread-like structure and colocalized with actin filaments but not with the microtubule network. CONCLUSION: These data support that C. neoformans internalization into HBMEC is a lipid raft/caveolae-dependent endocytic process where the actin cytoskeleton is involved, and the Cav1 plays an essential role in C. neoformans traversal of the blood-brain barrier. PMID- 22316087 TI - Geometry relaxation-induced large Stokes shift in red-emitting borondipyrromethenes (BODIPY) and applications in fluorescent thiol probes. AB - 2-Thienyl and 2,6-bisthienyl BODIPY derivatives (BS-SS and BS-DS) were prepared that show intense absorption (epsilon = 65000 M(-1) cm(-1) at 507 nm) and a large Stokes shift (96 nm) vs the small Stokes shift of typical BODIPY (<15 nm). Control compounds with a thienyl unit at the 8-position or phenyl substituents at the 2,6-positions were prepared (BS-1 and 9). BS-1 shows absorption/emission in the blue-shifted range and a small Stokes shift (12 nm). Compound 9 shows absorption in the red-shifted range, but the Stokes shift (<30 nm) is much smaller than that for BS-SS and BS-DS. DFT calculations propose the large Stokes shifts of BS-SS and BS-DS are due to the remarkable geometry relaxation upon photoexcitation and its substantial effect on the energy levels of molecular orbitals. For the dyes with small Stokes shifts, much smaller geometry relaxations were found. The fluorophores were used for fluorescent thiol probes, with 2,4-dinitrobenzenesulfonyl (DNBS) as the fluorescence switch. Both fluorescence OFF-ON and unprecedented ON-OFF transduction were observed, which are attributed to the different photoinduced intramolecular electron-transfer (PET) profile. All the photophysics were rationalized by DFT calculations based on the concept of "electronic states" instead of the very often used approximation of "molecular orbitals". PMID- 22316088 TI - Can racial disparities in optimal gout treatment be reduced? Evidence from a randomized trial. AB - There is a disproportionate burden of gout in African-Americans in the U.S. due to a higher disease prevalence and lower likelihood of receiving urate-lowering therapy (ULT), compared to Caucasians. There is an absence of strong data as to whether the response to ULT differs by race/ethnicity. BMC Musculoskeletal Disorders recently published a secondary analyses of the CONFIRMS trial, a large randomized controlled, double-blind trial of 2,269 gout patients. The authors reported that the likelihood of achieving the primary study efficacy end-point of achieving serum urate<6 mg/dl was similar between African-Americans and Caucasians, for all three treatment arms (Febuxostat 40 mg and 80 mg and allopurinol 300/200 mg). More importantly, rates were similar in subgroups of patients with mild or moderate renal insufficiency. Adverse event rates were similar, as were the rates of gout flares. These findings constitute a convincing evidence to pursue aggressive ULT in gout patients, regardless of race/ethnicity. This approach will likely help to narrow the documented racial disparities in gout care. Please see related article: http://www.biomedcentral.com/1471 2474/13/15. PMID- 22316089 TI - Reduction in duration of hypoglycemia by automatic suspension of insulin delivery: the in-clinic ASPIRE study. AB - BACKGROUND: The efficacy of automatic suspension of insulin delivery in induced hypoglycemia among subjects with type 1 diabetes was evaluated. SUBJECTS AND METHODS: In this randomized crossover study, subjects used a sensor-augmented insulin pump system with a low glucose suspend (LGS) feature that automatically stops insulin delivery for 2 h following a sensor glucose (SG) value <=70 mg/dL. Subjects fasted overnight and exercised until their plasma glucose (measured with the YSI 2300 STAT PlusTM glucose and lactate analyzer [YSI Life Sciences, Yellow Springs, OH]) value reached <=85 mg/dL on different occasions separated by washout periods lasting 3-10 days. Exercise sessions were done with the LGS feature turned on (LGS-On) or with continued insulin delivery regardless of SG value (LGS-Off). The order of LGS-On and LGS-Off sessions was randomly assigned. YSI glucose data were used to compare the duration and severity of hypoglycemia from successful LGS-On and LGS-Off sessions and to estimate the risk of rebound hyperglycemia after pump suspension. RESULTS: Fifty subjects attempted 134 sessions, 98 of which were successful. The mean+/-SD hypoglycemia duration was less during LGS-On than during LGS-Off sessions (138.5+/-76.68 vs. 170.7+/-75.91 min, P=0.006). During LGS-On compared with LGS-Off sessions, mean nadir YSI glucose was higher (59.5+/-5.72 vs. 57.6+/-5.69 mg/dL, P=0.015), as was mean end observation YSI glucose (91.4+/-41.84 vs. 66.2+/-13.48 mg/dL, P<0.001). Most (53.2%) end-observation YSI glucose values in LGS-On sessions were in the 70-180 mg/dL range, and none was >250 mg/dL. CONCLUSIONS: Automatic suspension of insulin delivery significantly reduced the duration and severity of induced hypoglycemia without causing rebound hyperglycemia. PMID- 22316090 TI - Delayed entry into HIV medical care after HIV diagnosis: risk factors and research methods. AB - Timely linkage to HIV medical care has the potential to improve individual health outcomes and prevent secondary HIV transmission. Recent research found that estimates of delayed care entry varied by study design, with higher estimates among studies using only HIV case surveillance data. In this analysis, we compared the prevalence and risk factors for care delay using data from two studies with different designs conducted in New York City. The Medical Monitoring Project (MMP) used a retrospective design to estimate historical delay among persons currently receiving care, while the Never in Care (NIC) study used a prospective design to estimate current delay status among persons who were care naive at baseline. Of 513 MMP subjects in 2007-2008, 23% had delayed care entry greater than three months after diagnosis. Independent risk factors for care delay were earlier year of diagnosis and testing positive in a nonmedical environment. Of 28 NIC subjects in 2008-2010, over half had tested positive in a nonmedical environment. The primary-stated reasons for delay were the same in both studies: denial of HIV status and lack of perceived need for medical care. The strengths and weaknesses of surveillance only, prospective, and retrospective study designs with respect to investigating this issue are explored. Future studies and interventions should be mindful of the common selection biases and measurement limitations with each design. A triangulation of estimates from varying designs is suggested for accurately measuring care linkage efforts over time. PMID- 22316091 TI - Lifestyle behavior pattern is associated with different levels of risk for incident dementia and Alzheimer's disease: the Cache County study. AB - OBJECTIVES: To identify distinct behavioral patterns of diet, exercise, social interaction, church attendance, alcohol consumption, and smoking and to examine their association with subsequent dementia risk. DESIGN: Longitudinal, population based dementia study. SETTING: Rural county in northern Utah, at-home evaluations. PARTICIPANTS: Two thousand four hundred ninety-one participants without dementia (51% male, average age 73.0 +/- 5,7; average education 13.7 +/- 4.1 years) initially reported no problems in activities of daily living and no stroke or head injury within the past 5 years. MEASUREMENTS: Six dichotomized lifestyle behaviors were examined (diet: high >= median on the Dietary Approaches to Stop Hypertension scale; exercise: >=5 h/wk of light activity and at least occasional moderate to vigorous activity; church attendance: attending church services at least weekly; social Interaction: spending time with family and friends at least twice weekly; alcohol: currently drinking alcoholic beverages >= 2 times/wk; nonsmoker: no current use or fewer than 100 cigarettes ever). Latent class analysis (LCA) was used to identify patterns among these behaviors. Proportional hazards regression modeled time to dementia onset as a function of behavioral class, age, sex, education, and apolipoprotein E status. Follow-up averaged 6.3 +/- 5.3 years, during which 278 cases of incident dementia (200 Alzheimer's disease (AD)) were diagnosed. RESULTS: LCA identified four distinct lifestyle classes. Unhealthy-religious (UH-R; 11.5%), unhealthy-nonreligious (UH NR; 10.5%), healthy-moderately religious (H-MR; 38.5%), and healthy-very religious (H-VR; 39.5%). UH-NR (hazard ratio (HR) = 0.54, P = .028), H-MR (HR = 0.56, P = .003), and H-VR (HR = 0.58, P = .005) had significantly lower dementia risk than UH-R. Results were comparable for AD, except that UH-NR was less definitive. CONCLUSION: Functionally independent older adults appear to cluster into subpopulations with distinct patterns of lifestyle behaviors with different levels of risk for subsequent dementia and AD. PMID- 22316092 TI - Peripheral blood gene expression changes during allergen inhalation challenge in atopic asthmatic individuals. AB - OBJECTIVES: (1) To investigate the effects of globin mRNA depletion in detecting differential gene expression in peripheral blood and (2) to investigate changes in peripheral blood gene expression in atopic asthmatic individuals undergoing allergen inhalation challenge. METHODS: Asthmatic subjects (20-60 years of age, with stable, mild allergic asthma, n = 9) underwent allergen inhalation challenges. All had an early asthmatic response of >=20% fall in forced expiratory volume in 1 second. Blood was collected immediately prior to and 2 hours after allergen challenge using PAXgene tubes (n = 4) and EDTA tubes (n = 5). Aliquots of the PAXgene blood samples were subjected to globin reduction (PAX GR). Transcriptome analysis was performed using Affymetrix GeneChip((r)) Human Gene 1.0 ST arrays. Data were preprocessed using factor analysis for robust microarray summarization and analyzed using linear models for microarrays. Pathway analyses were performed using Ingenuity Pathway Analysis. RESULTS: Globin reduction uncovered probe sets of lower abundance. However, it significantly reduced the ability to detect differentially expressed genes (DEGs) when compared to non-globin-reduced PAXgene samples (PAX-NGR). Combined transcriptional analysis of four PAX-NGR and five EDTA sample pairs identified 1595 DEGs associated with allergen inhalation challenge (false discovery rate <= 5%), with the top-ranked network of perturbed biological functions consisting of inflammatory response, cellular movement, and immune cell trafficking. CONCLUSIONS: While we have demonstrated a diminished ability to detect DEGs after globin reduction, we have nevertheless identified significant changes in the peripheral blood transcriptome of people with mild asthma 2 hours after allergen inhalation challenge. PMID- 22316094 TI - C and O stable isotopic signatures of fast-growing dripstones on alkaline substrates: reflection of growth mechanism, carbonate sources and environmental conditions. AB - Secondary carbonate precipitates (dripstones) formed on concrete surfaces in four different environments--Mediterranean and continental open-space and indoor environments (inside a building and in a karstic cave)--were studied. The fabric of dripstones depends upon water supply, pH of mother solution and carbonate resulting precipitation rate. Very low delta(13)C (average-28.20/00) and delta(18)O (average-18.40/00) values showed a strong positive correlation, typical for carbonate precipitated by rapid dissolution of CO(2) in a highly alkaline solution and consequent disequilibrium precipitation of CaCO(3). The main source of carbon is atmospheric or biogenic CO(2) in the poorly ventilated karstic cave, which is reflected in even lower delta(13)C values. Statistical analysis of delta(13)C and delta(18)O values of the four groups of samples showed that the governing factor of isotope fractionation is not the temperature, but rather the precipitation rate. PMID- 22316093 TI - Towards a quantitative understanding of the MITF-PIAS3-STAT3 connection. AB - BACKGROUND: Expression of the two transcription factors microphthalmia-associated transcription factor (MITF) and signal transducer and activator of transcription 3 (STAT3) are tightly connected to cell proliferation and survival, and are important for melanocyte development. The co-regulation of MITF and STAT3 via their binding to a common inhibitor Protein Inhibitor of Activated STAT3 (PIAS3) is intriguing. A better quantitative understanding of this regulation is likely to be important for elucidation of the melanocyte biology. RESULTS: We present a mathematical model describing the MITF-PIAS3-STAT3 signalling network. A default parameter set was developed, partly informed by the literature and partly by constraining the model to mimic reported behavioural features of the system. In addition, a set of experiment-specific parameters was derived for each of 28 experiments reported in the literature. The model seems capable of accounting for most of these experiments in terms of observed temporal development of protein amounts and phosphorylation states. Further, the results also suggest that this system possesses some regulatory features yet to be elucidated. CONCLUSIONS: We find that the experimentally observed crosstalk between MITF and STAT3 via PIAS3 in melanocytes is faithfully reproduced in our model, offering mechanistic explanations for this behaviour, as well as providing a scaffold for further studies of MITF signalling in melanoma. PMID- 22316095 TI - Probing the surface structure of divalent transition metals using surface specific solid-state NMR spectroscopy. AB - Environmental and geochemical systems containing paramagnetic species could benefit by using nuclear magnetic resonance (NMR) spectroscopy due to the sensitivity of the spectral response to small amounts paramagnetic interactions. In this study, we apply commonly used solid-state NMR spectroscopic methods combined with chemometrics analysis to probe sorption behavior of the paramagnetic cations Cu(2+) and Ni(2+)at the amorphous silica surface. We exploit the unique properties of paramagnets to derive meaningful structural information in these systems at low, environmentally relevant cation surface loadings by comparing the NMR response of sorption samples to paramagnetic free samples. These data suggest that a simple sorption model where the cation sorbs as inner sphere complexes at negatively charged, deprotonated silanol sites is appropriate. These results help constrain sorption models that are used to describe metal fate and transport. PMID- 22316097 TI - A handoff is not a telegram: an understanding of the patient is co-constructed. AB - Hospital handoffs are believed to be a key locus of communication breakdown that can endanger patient safety and undermine quality of care. Substantial new efforts to better understand handoffs and to improve handoff practices are under way. Many such efforts appear to be seriously hampered, however, by an underlying presumption that the essential function of a handoff is one-way information transmission. Here, we examine social science literature that supports a richer framing of handoff conversations, one that characterizes them as co-constructions of an understanding of the patient. PMID- 22316098 TI - Why are SiX5(-) and GeX5(-) (X = F, Cl) stable but not CF5(-) and CCl5(-)? AB - The possible existence of the CF(5)(-), CCl(5)(-), SiF(5)(-), SiCl(5)(-), GeF(5)( ), and GeCl(5)(-) anions has been investigated using ab initio methods. The species containing Si and Ge as central atoms were found to adopt the D(3h) symmetry trigonal bipyramidal equilibrium structures whose thermodynamic stabilities were confirmed by examining the most probable fragmentation channels. The ab initio re-examination of the electronic stabilities of the SiF(5)(-), SiCl(5)(-), GeF(5)(-), and GeCl(5)(-) anions [using the OVGF(full) method with the 6-311+G(3df) basis set] led to the very large vertical electron detachment (VDE) energies of 9.316 eV (SiF(5)(-)) and 9.742 eV (GeF(5)(-)), whereas smaller VDEs of 6.196 and 6.452 eV were predicted for the SiCl(5)(-) and GeCl(5)(-) species, respectively. By contrast, the high-symmetry and structurally compact anionic CF(5)(-) and CCl(5)(-) systems cannot exist due to the strongly repulsive potential predicted for the X(-) (F(-) or Cl(-)) approaching the CX(4) (CF(4) or CCl(4)). The formation of weakly bound CX(4)...X(-) (CF(4)...F(-) and CCl(4)...Cl(-)) anionic complexes (consisting of pseudotetrahedral neutral CX(4) with the weakly tethered X(-)) might be expected at low temperatures (approaching 0 K), whereas neither CX(5)(-) (CF(5)(-), CCl(5)(-)) systems nor CX(4)...X(-) (CF(4)...F(-) and CCl(4)...Cl(-)) complexes can exist in the elevated temperatures (above 0K) due to their susceptibility to the fragmentation (leading to the X(-) loss). PMID- 22316100 TI - Strain-promoted azide-alkyne cycloadditions of benzocyclononynes. AB - Preliminary studies related to the design and development of new cycloalkyne reagents for metal-free click coupling are reported. Cyclononynes are more stable than cyclooctynes, and the robust benzocyclononyne platform offers spontaneous reactivity toward azides at rates competitive with other azidophiles that have been employed for metal-free click coupling. Benzocyclononynes (e.g., 1) provide valuable insight into the design of new cycloalkynes for strain-promoted azide alkyne cycloaddition (SPAAC) couplings for applications in which side reactions and decomposition of the reagent must be kept to a minimum. PMID- 22316101 TI - Inductively coupled microfluidic pressure meter for in vivo monitoring of cerebrospinal fluid shunt function. AB - A microfluidic pressure sensor with inductively coupled, wireless readout capability has been developed for integration into cerebrospinal fluid shunt valve implants. The sensor consists of a deformable PDMS film that is bonded over a microfluidic reservoir, forming a fluidic capacitor. Deflection of the capacitor membrane is detected remotely through a shift in the resonance frequency of a micro-fabricated LC circuit. Sensors were fabricated by a combination of conventional MEMS technologies and rapid soft lithography. A direct pattern transfer technique was used to pattern the deformable PDMS film with a metal coating for the capacitive readout. The mechanical response of the fluidic capacitor was characterized by measuring the deflection of the PDMS film using an extrinsic Fabry-Perot interferometer (EFPI), and wireless sensing was demonstrated by the shift in resonance frequency of the sensor via an inductively coupled antenna. The sensor transduces pressure into a change in resonant frequency with sensitivity > 3.4 ppm Pa-1 and responsivity 4.6 kHz Pa-1, over a dynamic range of 0~3 kPa. PMID- 22316102 TI - What contributes to self-rated oral health among community-dwelling older adults? Findings from the ElderSmile program. AB - OBJECTIVES: As part of ongoing efforts by the Columbia University College of Dental Medicine to devise community-based models of health promotion and care for local residents, we sought to answer the following query: "What contributes to self-rated oral health among community-dwelling older adults?" METHODS: The present study is cross sectional in design and centrally concerned with baseline data collected during community-based screenings of adults aged 50 years and older who agreed to participate in the ElderSmile program in northern Manhattan, New York City. The primary outcome measure of interest is self-rated oral health, which was assessed as follows: "Overall, how would you rate the health of your teeth and gums - excellent, good, fair, or poor?" RESULTS: More than a quarter (28.5 percent) of ElderSmile participants aged 50 years and older reported that their oral health was poor. After adjustment for age (in years), place of birth, educational level, and dental insurance status in a logistic regression model, recent visits to the dentist (within the past year versus more than a year ago) contributed to better self-rated oral health and non-Hispanic Black race/ethnicity, dentate (versus edentulous) status, tooth decay as measured by decayed missing filled teeth, and severe periodontal inflammation contributed to worse self-rated oral health in this population. CONCLUSIONS: Recent dental care contributed to better self-rated oral health among community-dwelling older adults living in northern Manhattan. Significant gradients were evident in the caries experience and periodontal inflammation of dentate adults by self-rated oral health, suggesting that untreated oral disease contributes to poor self rated oral health. PMID- 22316103 TI - Consensus embedding: theory, algorithms and application to segmentation and classification of biomedical data. AB - BACKGROUND: Dimensionality reduction (DR) enables the construction of a lower dimensional space (embedding) from a higher dimensional feature space while preserving object-class discriminability. However several popular DR approaches suffer from sensitivity to choice of parameters and/or presence of noise in the data. In this paper, we present a novel DR technique known as consensus embedding that aims to overcome these problems by generating and combining multiple low dimensional embeddings, hence exploiting the variance among them in a manner similar to ensemble classifier schemes such as Bagging. We demonstrate theoretical properties of consensus embedding which show that it will result in a single stable embedding solution that preserves information more accurately as compared to any individual embedding (generated via DR schemes such as Principal Component Analysis, Graph Embedding, or Locally Linear Embedding). Intelligent sub-sampling (via mean-shift) and code parallelization are utilized to provide for an efficient implementation of the scheme. RESULTS: Applications of consensus embedding are shown in the context of classification and clustering as applied to: (1) image partitioning of white matter and gray matter on 10 different synthetic brain MRI images corrupted with 18 different combinations of noise and bias field inhomogeneity, (2) classification of 4 high-dimensional gene expression datasets, (3) cancer detection (at a pixel-level) on 16 image slices obtained from 2 different high-resolution prostate MRI datasets. In over 200 different experiments concerning classification and segmentation of biomedical data, consensus embedding was found to consistently outperform both linear and non-linear DR methods within all applications considered. CONCLUSIONS: We have presented a novel framework termed consensus embedding which leverages ensemble classification theory within dimensionality reduction, allowing for application to a wide range of high-dimensional biomedical data classification and segmentation problems. Our generalizable framework allows for improved representation and classification in the context of both imaging and non-imaging data. The algorithm offers a promising solution to problems that currently plague DR methods, and may allow for extension to other areas of biomedical data analysis. PMID- 22316104 TI - Four-component assembly of chiral N-B heterocycles with a natural product-like framework. AB - The dative N-B bond was used to simply assemble heterocycles with a skeleton akin to the 5-oxofuro[2,3-b]furan motif. Twenty-five new N-B heterocycles were prepared via a highly efficient one-pot four-component reaction in yields and diastereoselectivities up to 95% and >97%, respectively. Several reaction intermediates were discovered using electrospray ionization mass spectroscopy which set the basis for the mechanism elucidation using DFT calculations. PMID- 22316105 TI - Access to oral health services for urban low-income Latino children: social ecological influences. AB - OBJECTIVES: Using an ecological conceptual model, this study examined the social context, structural, and behavioral factors within an immigrant community that contribute to increased access and use of oral health services by Latino children. The predictors of health service use at the level of the individual, the family, the provider, and the health service system were studied for their effects on the initiation of care, continuity of care, and frequency of planned visits. METHODS: In-depth face-to-face interviews were conducted with 320 Latino mothers regarding their use of oral health services for 4-8-year-old children [Mexican (n = 221), Puerto Rican (n = 69), and Central and South American (n = 30)]. Outcome measures of dental care utilization were early age at initiation of care, continuity of care, and frequency of planned dental visits. RESULTS: Regular planned dental visits were significantly related to the structural variables of household income and provider availability. The initiation of dental care was related to the mother's beliefs about the value of early preventive dental care. Mothers were more likely to continue care if they believed that the purpose was to keep the child's teeth healthy and had satisfactory communication with the dentist. CONCLUSIONS: Identifying the structural and behavioral factors that increase the likelihood of the use of oral health services can provide the basis for developing effective interventions specific to Latino children at the neighborhood level. The study findings can be also used for designing culturally appropriate oral health promotion programs and provider coordination of care. PMID- 22316106 TI - African American patients with gout: efficacy and safety of febuxostat vs allopurinol. AB - BACKGROUND: African Americans are twice as likely as Caucasians to develop gout, but they are less likely to be treated with urate-lowering therapy (ULT). Furthermore, African Americans typically present with more comorbidities associated with gout, such as hypertension, obesity, and renal impairment. We determined the efficacy and safety of ULT with febuxostat or allopurinol in African American subjects with gout and associated comorbidities and in comparison to Caucasian gout subjects. METHODS: This is a secondary analysis of the 6-month Phase 3 CONFIRMS trial. Eligible gouty subjects with baseline serum urate (sUA) >= 8.0 mg/dL were randomized 1:1:1 to receive febuxostat 40 mg, febuxostat 80 mg, or allopurinol (300 mg or 200 mg depending on renal function) daily. All subjects received gout flare prophylaxis. Primary efficacy endpoint was the proportion of subjects in each treatment group with sUA < 6.0 mg/dL at the final visit. Additional endpoints included the proportion of subjects with mild or with moderate renal impairment who achieved a target sUA < 6.0 mg/dL at final visit. Adverse events (AEs) were recorded throughout the study. RESULTS: Of the 2,269 subjects enrolled, 10.0% were African American and 82.1% were Caucasian. African American subjects were mostly male (89.5%), obese (BMI >= 30 kg/m2; 67.1%), with mean baseline sUA of 9.8 mg/dL and mean duration of gout of 10.4 years. The proportions of African American subjects with a baseline history of diabetes, renal impairment, or cardiovascular disease were significantly higher compared to Caucasians (p < 0.001). ULT with febuxostat 80 mg was superior to both febuxostat 40 mg (p < 0.001) and allopurinol (p = 0.004). Febuxostat 40 mg was comparable in efficacy to allopurinol. Significantly more African American subjects with mild or moderate renal impairment achieved sUA < 6.0 mg/dL in the febuxostat 80 group than in either the febuxostat 40 mg or allopurinol group (p < 0.05). Efficacy rates in all treatment groups regardless of renal function were comparable between African American and Caucasian subjects, as were AE rates. CONCLUSIONS: In African American subjects with significant comorbidities, febuxostat 80 mg is significantly more efficacious than either febuxostat 40 mg or allopurinol 200/300 mg. Febuxostat was well tolerated in this African American population.Please see related article: http://www.biomedcentral.com/1741 7015/10/15. PMID- 22316107 TI - Kinetic study of the alpha-tocopherol-regeneration reaction of ubiquinol-10 in methanol and acetonitrile solutions: notable effect of the alkali and alkaline earth metal salts on the reaction rates. AB - A kinetic study of regeneration reaction of alpha-tocopherol (alpha-TocH) by ubiquinol-10 has been performed in the presence of four kinds of alkali and alkaline earth metal salts (LiClO(4), NaClO(4), NaI, and Mg(ClO(4))(2)) in methanol and acetonitrile solutions, using double-mixing stopped-flow spectrophotometry. The second-order rate constants (k(r)'s) for the reaction of alpha-tocopheroxyl (alpha-Toc*) radical with ubiquinol-10 increased and decreased notably with increasing concentrations of metal salts in methanol and acetonitrile, respectively. The k(r) values increased in the order of no metal salt < NaClO(4) ~ NaI < LiClO(4) < Mg(ClO(4))(2) at the same concentration of metal salts in methanol. On the other hand, in acetonitrile, the k(r) values decreased in the order of no metal salt > NaClO(4) ~ NaI > LiClO(4) > Mg(ClO(4))(2) at the same concentration of metal salts. The metal salts having a smaller ionic radius of cation and a larger charge of cation gave a larger k(r) value in methanol, and a smaller k(r) value in acetonitrile. The effect of anion was almost negligible in both the solvents. Notable effects of metal cations on the UV-vis absorption spectrum of alpha-Toc* radical were observed in aprotic acetonitrile solution, suggesting complex formation between alpha-Toc* and metal cations. On the other hand, effects of metal cations were negligible in protic methanol, suggesting that the complex formation between alpha-Toc* and metal cations is hindered by the hydrogen bond between alpha-Toc* and methanol molecules. The difference between the reaction mechanisms in methanol and acetonitrile solutions was discussed on the basis of the results obtained. High concentrations of alkali and alkaline earth metal salts coexist with alpha-TocH and ubiquinol-10 in plasma, blood, and many tissues, suggesting the contribution of the metal salts to the above regeneration reaction in biological systems. PMID- 22316108 TI - Only connect--the role of PLHIV group networks in increasing the effectiveness of Ugandan HIV services. AB - In recent years, Uganda has experienced rapid growth in networked groups of people living with HIV (PLHIV) who provide support, engage in advocacy, treatment and care and raise the profile of HIV in the public domain. This qualitative study focused the benefits of joining a networked group, relationships between groups, impact of networked groups on the community and shaping private and public experience living with HIV. Data were collected from two Ugandan districts, using semi-structured interviews, focus group discussions (FGDs), observation and reviews of group records and archives. Respondents (n=46) were adults living with HIV, and members of rural and urban PLHIV groups. Narratives from PLHIV (n=27) were gathered, and records from PLHIV group service-registers (n=20) reviewed. Key Informants (n=15) were purposively selected for interview, based on participation in PLHIV groups, utilisation of network services and their positions as key stakeholders. FGDs were held with network support agents (NSAs), members of PLHIV groups, and their leaders. Following qualitative analysis, findings suggest that for respondents, PLHIV networks enhance the impact and effectiveness of individual groups: the whole is greater than the sum of the parts. For groups, being part of a wider network allows for diversity of service delivery, and well-defined roles for individuals to participate in community support and sensitisation, with a reduction in the experience of stigma. We conclude that networking PLHIV groups is an effective strategy for improving the quality and reach of community-based HIV services. Governments should be encouraged to support networks and include them in policy-making at the national level. Local and regional groups should explore further ways to collaborate and expand support to PLHIV in Uganda. PMID- 22316109 TI - Functional analysis of Pro-inflammatory properties within the cerebrospinal fluid after subarachnoid hemorrhage in vivo and in vitro. AB - BACKGROUND: To functionally characterize pro-inflammatory and vasoconstrictive properties of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage (SAH) in vivo and in vitro. METHODS: The cerebrospinal fluid (CSF) of 10 patients suffering from SAH was applied to the transparent skinfold chamber model in male NMRI mice which allows for in vivo analysis of the microcirculatory response to a superfusat. Microvascular diameter changes were quantified and the numbers of rolling and sticking leukocytes were documented using intravital multifluorescence imaging techniques. Furthermore, the pro-inflammatory properties of CSF were assessed in vitro using a monocyte transendothelial migration assay. RESULTS: CSF superfusion started to induce significant vasoconstriction on days 4 and 6 after SAH. In parallel, CSF superfusion induced a microvascular leukocyte recruitment, with a significant number of leukocytes rolling (day 6) and sticking (days 2-4) to the endothelium. CSF of patients presenting with cerebral edema induced breakdown of blood vessel integrity in our assay as evidenced by fluorescent marker extravasation. In accordance with leukocyte activation in vivo, significantly higher in vitro monocyte migration rates were found after SAH. CONCLUSION: We functionally characterized inflammatory and vasoactive properties of patients' CSF after SAH in vivo and in vitro. This pro-inflammatory milieu in the subarachnoid space might play a pivotal role in the pathophysiology of early and delayed brain injury as well as vasospasm development following SAH. PMID- 22316110 TI - Predicting asthma treatment outcome at diagnosis: the role of symptom perception during a histamine challenge test. AB - OBJECTIVE: In asthma, many treatment decisions are dependent upon patient perception/patient report of asthma symptoms. Discrepancies between patient perception of asthma symptoms and objective indicators of pathophysiology are widespread and can hinder asthma treatment. Early detection of problems in asthma symptom perception may be a first step to help these patients. We investigated the predictive value of symptom perception during a histamine challenge test (HCT) at asthma diagnosis for patient-rated outcome of asthma treatment 3 months later. METHODS: In a prospective observational study, persons with asthma (N = 60) showing bronchial hyperresponsiveness in a HCT completed questions on asthma symptoms and negative affectivity (NA). The HCT was extended with an ambiguous situation suggesting asthma symptoms despite physiological recovery. Lung function (forced expiratory volume in 1 second (FEV(1))) and symptom ratings were measured during the test (after each histamine dosage), and we constructed several measures of asthma symptom perception based on FEV(1) and symptom ratings. Three months later, 30 participants completed questionnaires on asthma control and asthma-related quality of life. RESULTS: Symptoms reported during HCT predicted worse asthma control and quality of life 3 months later. The prospective association between symptoms during HCT and asthma control remained significant when controlling for NA and baseline lung function. These effects were strongest for symptoms during ambiguous situations. CONCLUSIONS: Higher symptom levels at the start of the HCT and during recovery may reflect a tendency to inaccurately perceive asthma symptoms in ambiguous situations. Assessing symptoms during diagnostic challenge tests can help predict problems with asthma treatment. PMID- 22316111 TI - High-fiber foods reduce periodontal disease progression in men aged 65 and older: the Veterans Affairs normative aging study/Dental Longitudinal Study. AB - OBJECTIVES: To determine whether foods that are good to excellent sources of fiber reduce periodontal disease progression in men. DESIGN: Prospective, observational study. SETTING: Greater Boston, Massachusetts, metropolitan area. PARTICIPANTS: Six hundred twenty-five community-dwelling men participating in the Department of Veterans Affairs Dental Longitudinal Study. MEASUREMENTS: Dental and physical examinations were conducted every 3 to 5 years. Diet was assessed using food frequency questionnaires (FFQs). Mean follow-up was 15 years (range: 2 24 years). Periodontal disease progression on each tooth was defined as alveolar bone loss (ABL) advancement of 40% or more, probing pocket depth (PPD) of 2 mm or more, or tooth loss. Good and excellent fiber sources provided 2.5 g or more of fiber per serving. Multivariate proportional hazards regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of periodontal disease progression and tooth loss in relation to fiber sources, stratified according to age younger than 65 versus 65 and older, and controlled for smoking, body mass index, calculus, baseline periodontal disease level, caries, education, exercise, carotene, thiamin and caffeine intake, and tooth brushing. RESULTS: In men aged 65 and older, each serving of good to excellent sources of total fiber was associated with lower risk of ABL progression (HR = 0.76, 95% CI = 0.60-0.95) and tooth loss (HR = 0.72, 95% CI = 0.53-0.97). Of the different food groups, only fruits that were good to excellent sources of fiber were associated with lower risk of progression of ABL (HR = 0.86 per serving, 95% CI = 0.78-0.95), PPD (HR = 0.95, 95% CI = 0.91-0.99), and tooth loss (HR = 0.88, 95% CI = 0.78-0.99). No significant associations were seen in men younger than 65. CONCLUSION: Benefits of higher intake of high-fiber foods, especially fruits, on slowing periodontal disease progression are most evident in men aged 65 and older. PMID- 22316112 TI - Pseudohalides of boron subphthalocyanine. AB - The synthesis and study of a series of pseudohalides of boron subphthalocyanine (BsubPc) are reported. Each pseudohalide has been compared to the more common chloride and bromide of BsubPc, and we have found that most react slower under standard phenoxylation and hydrolysis conditions. Three pseudohalides (TsO BsubPc, MsO-BsubPc, and BsO-BsubPc) do not hydrolyze at all even after prolonged periods of time in the presence of water. Single crystals of TsO-, MsO-, and ClsO BsubPc were obtained, and their structures were unambiguously determined. PMID- 22316113 TI - Fluorescence enhancement of di-p-tolyl viologen by complexation in cucurbit[7]uril. AB - A viologen derivative, 1,1'-di-p-tolyl-(4,4'-bipyridine)-1,1'-diium dichloride (DTV(2+)), was studied in solution and encapsulated in cucurbit[7]uril (CB7), a macrocyclic host. Upon encapsulation, DTV(2+) exhibited dramatically enhanced fluorescence. Aqueous solutions of DTV(2+) were weakly fluorescent (Phi = 0.01, tau < 20 ps), whereas the emission of the DTV(2+)@2CB7 complex was enhanced by 1 order of magnitude (Phi = 0.12, tau = 0.7 ns) and blue-shifted by 35 nm. Similar properties were observed in the presence of NaCl. DTV(2+) in a poly(methyl methacrylate) matrix was fluorescent with a spectrum similar to that observed for the complex in solution. (1)H NMR and UV-vis titrations indicated that the DTV(2+)@2CB7 complex is formed in aqueous solutions with complexation constants K(1) = (1.2 +/- 0.3) * 10(4) M(-1) and K(2)= (1.0 +/- 0.4) * 10(4) M(-1) in water. Density functional theory and configuration interaction singles calculations suggested that the hindrance of the rotational relaxation of the S(1) state of DTV(2+) caused by encapsulation within the host or a polymer matrix plays a key role in the observed emission enhancement. The absorption and emission spectra of DTV(2+)@2CB7 in water exhibited a large Stokes shift (DeltaSt ~ 9000 cm(-1)) and no fine structure. DTV(2+) is a good electron acceptor [E degrees (DTV(2+)/DTV(*+)) = -0.30 V vs Ag/AgCl] and a strong photooxidant [E degrees (DTV*(2+)/DTV(*+)) = 0.09 V vs NHE]). PMID- 22316114 TI - Effect of miglitol as an add-on to bolus insulin on postprandial glycemic excursions in type 2 diabetes patients assessed by continuous glucose monitoring. AB - BACKGROUND: We compared the effects of miglitol as an add-on to bolus insulin and dose-intensified bolus insulin on postprandial glycemic excursions by continuous glucose monitoring (CGM). SUBJECTS AND METHODS: The glucose levels of 21 type 2 diabetes patients admitted for glycemic control were monitored for three consecutive days by CGM after stable glycemic control was achieved with bolus or basal-bolus insulin therapy. During the 3-day period, bolus insulin administration was continued in 11 patients on Day 1; the dose of bolus insulin in these patients was increased by 2 U before each meal on day 2, and on day 3, 50 mg of miglitol was administered before each meal in addition to the initial dose of bolus insulin given on Day 1. In the remaining 10 patients, the order of administration on Day 2 and Day 3 was reversed. RESULTS: Of the glycemic fluctuations observed during the 24-h period, postprandial glycemic excursions showed a greater reduction during treatment with dose-intensified bolus insulin and during treatment with miglitol plus bolus insulin than during treatment with bolus insulin alone; however, miglitol plus bolus insulin treatment had a more potent effect than treatment with dose-intensified bolus insulin on reducing postprandial glycemic excursions immediately after meals. Changes in area under the curve (DeltaAUC) occurring within 1 h and 2 h after each meal were significantly smaller during treatment with miglitol plus bolus insulin than during treatment with dose-intensified bolus insulin, whereas DeltaAUC within >2 h after each meal, except dinner, was significantly greater during treatment with miglitol plus bolus insulin than during treatment with dose-intensified bolus insulin. CONCLUSION: Our findings suggest that miglitol as an add-on to bolus insulin in patients with type 2 diabetes may be one of the beneficial therapeutic options that provides a more rigorous postprandial glycemic control without increasing the risk for hypoglycemia before the next meal. PMID- 22316115 TI - Biological conversion assay using Clostridium phytofermentans to estimate plant feedstock quality. AB - BACKGROUND: There is currently considerable interest in developing renewable sources of energy. One strategy is the biological conversion of plant biomass to liquid transportation fuel. Several technical hurdles impinge upon the economic feasibility of this strategy, including the development of energy crops amenable to facile deconstruction. Reliable assays to characterize feedstock quality are needed to measure the effects of pre-treatment and processing and of the plant and microbial genetic diversity that influence bioconversion efficiency. RESULTS: We used the anaerobic bacterium Clostridium phytofermentans to develop a robust assay for biomass digestibility and conversion to biofuels. The assay utilizes the ability of the microbe to convert biomass directly into ethanol with little or no pre-treatment. Plant samples were added to an anaerobic minimal medium and inoculated with C. phytofermentans, incubated for 3 days, after which the culture supernatant was analyzed for ethanol concentration. The assay detected significant differences in the supernatant ethanol from wild-type sorghum compared with brown midrib sorghum mutants previously shown to be highly digestible. Compositional analysis of the biomass before and after inoculation suggested that differences in xylan metabolism were partly responsible for the differences in ethanol yields. Additionally, we characterized the natural genetic variation for conversion efficiency in Brachypodium distachyon and shrub willow (Salix spp.). CONCLUSION: Our results agree with those from previous studies of lignin mutants using enzymatic saccharification-based approaches. However, the use of C. phytofermentans takes into consideration specific organismal interactions, which will be crucial for simultaneous saccharification fermentation or consolidated bioprocessing. The ability to detect such phenotypic variation facilitates the genetic analysis of mechanisms underlying plant feedstock quality. PMID- 22316116 TI - Monte Carlo modelling of human body for dose conversion coefficients of 137Cs in soil of the Eastern Black Sea region of Turkey. AB - Absorbed dose conversion coefficients for a human body standing on the soil surface were calculated for (137)Cs in the soil of Eastern Black Sea region of Turkey using the Monte Carlo simulation method. The results were given in nGy h( 1) per Bq cm(-2) as a function of depth. Simple numerical integration of this function multiplied with the known specific activity as a function of depth gives the absorbed dose conversion coefficients for any distribution of (137)Cs in soil. Gaussian distribution of (137)Cs in the soil was considered for calculations. PMID- 22316117 TI - Direct use of esters in the Mukaiyama aldol reaction: a powerful and convenient alternative to aldehydes. AB - An indium triiodide catalyst promoted the direct transformation from esters to beta-hydroxycarbonyl compounds using hydrosilanes and silyl enolates by a one stage process. Various esters were applicable, and the high chemoselectivity of this system brings compatibility to many functional groups: alkenyl, alkynyl, chloro, and hydroxy. PMID- 22316118 TI - Clinical review: sepsis and septic shock--the potential of gene arrays. AB - Over the past decade several investigators have applied microarray technology and related bioinformatic approaches to clinical sepsis and septic shock, thus allowing for an assessment of how, or if, this branch of genomic medicine has meaningfully impacted the field of sepsis research. The ability to simultaneously and efficiently measure the steady-state mRNA abundance of thousands of transcripts from a given tissue source (that is, 'transcriptomics') has provided an unprecedented opportunity to gain a broader, genome-level 'picture' of complex and heterogeneous clinical syndromes such as sepsis. A trancriptomic approach to sepsis and septic shock is technically challenging on multiple levels, but nonetheless modest, tangible advances are being realized. These include a genome level understanding of the complexity of sepsis and septic shock, identification of novel candidate pathways and targets for potential intervention, discovery of novel, candidate diagnostic and stratification biomarkers, and the ability to stratify patients into clinically relevant, expression-based subclasses. The challenges moving forward include robust validation studies, standardization of technical approaches, standardization and further development of analytical algorithms, and large-scale collaborations. PMID- 22316119 TI - Inaccuracies in total serum IgE measurements by immulite caused by omalizumab in specimens. PMID- 22316120 TI - Examiner reliability of fluorosis scoring: a comparison of photographic and clinical examination findings. AB - OBJECTIVE: To assess and compare examiner reliability of clinical and photographic fluorosis examinations using the Fluorosis Risk Index (FRI) among children in the Iowa Fluoride Study (IFS). METHODS: The IFS examined 538 children for fluorosis and dental caries at age 13 and obtained intraoral photographs from nearly all of them. To assess examiner reliability, duplicate clinical examinations were conducted for 40 of the subjects. In addition, 200 of the photographs were scored independently for fluorosis by two examiners in a standardized manner. Fluorosis data were compared between examiners for the clinical exams and separately for the photographic exams, and a comparison was made between clinical and photographic exams. For all three comparisons, examiner reliability was assessed using kappa statistics at the tooth level. RESULTS: Interexaminer reliability for the duplicate clinical exams on the sample of 40 subjects as measured by kappa was 0.59, while the repeat exams of the 200 photographs yielded a kappa of 0.64. For the comparison of photographic and clinical exams, interexaminer reliability, as measured by weighted kappa, was 0.46. FRI scores obtained using the photographs were higher on average than those obtained from the clinical exams. Fluorosis prevalence was higher for photographs (33 percent) than found for clinical exam (18 percent). CONCLUSION: Results suggest that interexaminer reliability is greater and fluorosis scores are higher when using photographic compared with clinical examinations. PMID- 22316121 TI - DQB1*0602 rather than DRB1*1501 confers susceptibility to multiple sclerosis-like disease induced by proteolipid protein (PLP). AB - BACKGROUND: Multiple sclerosis (MS) is associated with pathogenic autoimmunity primarily focused on major CNS-myelin target antigens including myelin basic protein (MBP), proteolipidprotein (PLP), myelin oligodendrocyte protein (MOG). MS is a complex trait whereby the HLA genes, particularly class-II genes of HLA-DR15 haplotype, dominate the genetic contribution to disease-risk. Due to strong linkage disequilibrium in HLA-II region, it has been hard to establish precisely whether the functionally relevant effect derives from the DRB1*1501, DQA1*0102 DQB1*0602, or DRB5*0101 loci of HLA-DR15 haplotype, their combinations, or their epistatic interactions. Nevertheless, most genetic studies have indicated DRB1*1501 as a primary risk factor in MS. Here, we used 'HLA-humanized' mice to discern the potential relative contribution of DRB1*1501 and DQB1*0602 alleles to susceptibility to "humanized" MS-like disease induced by PLP, one of the most prominent and encephalitogenic target-antigens implicated in human MS. METHODS: The HLA-DRB1*1501- and HLA-DQB1*0602-Tg mice (MHC-II(-/-)), and control non-HLA DR15-relevant-Tg mice were immunized with a set of overlapping PLP peptides or with recombinant soluble PLP for induction of "humanized" MS-like disease, as well as for ex-vivo analysis of immunogenic/immunodominant HLA-restricted T-cell epitopes and associated cytokine secretion profile. RESULTS: PLP autoimmunity in both HLA-DR15-Tg mice was focused on 139-151 and 175-194 epitopes. Strikingly, however, the HLA-DRB1*1501-transgenics were refractory to disease induction by any of the overlapping PLP peptides, while HLA-DQB1*0602 transgenics were susceptible to disease induction by PLP139-151 and PLP175-194 peptides. Although both transgenics responded to both peptides, the PLP139-151- and PLP175-194 reactive T-cells were directed to Th1/Th17 phenotype in DQB1*0602-Tg mice and towards Th2 in DRB1*1501-Tg mice. CONCLUSIONS: While genome studies map a strong MS susceptibility effect to the region of DRB1*1501, our findings offer a rationale for potential involvement of pathogenic DQ6-associated autoimmunity in MS. Moreover, that DQB1*0602, but not DRB1*1501, determines disease susceptibility to PLP in HLA-transgenics, suggests a potential differential, functional role for DQB1*0602 as a predisposing allele in MS. This, together with previously demonstrated disease-susceptibility to MBP and MOG in DRB1*1501 transgenics, also suggests a differential role for DRB1*1501 and DQB1*0602 depending on target antigen and imply a potential complex 'genotype/target antigen/phenotype' relationship in MS heterogeneity. PMID- 22316122 TI - To whom do the results of the multicenter, randomized, controlled INSECT trial (ISRCTN 24023541) apply?--assessment of external validity. AB - A response to Seiler et al: Interrupted or continuous slowly absorbable sutures for closure of primary elective midline abdominal incisions: a multicenter randomized trial (INSECT: ISRCTN24023541). Ann Surg 2009, 249(4):576-582. BACKGROUND: Existing evidence suggests that the transfer of results of randomized controlled trials into clinical practice may be limited. Potential reasons can be attributed to aspects of external validity. The aim of this study is to investigate issues related to the external validity of the INSECT trial. METHODS: All participating surgical departments were categorized and the clinical and baseline characteristics of randomized patients were evaluated. In addition, demographic and clinical data of all screened and randomized patients at the Departments of Surgery in Heidelberg and Erlangen were analyzed. RESULTS: Twenty five centers enrolled a total of 625 patients. These centers included eight primary, 11 secondary, and six tertiary care centers. The tertiary care centers enrolled the most patients (n = 237, 38%) followed by the primary care centers (n = 199, 32%) and the secondary care centers (n = 189 patients; 30%). The mean number and baseline data of randomized patients did not differ between the three types of care centers (p = 0.09). Overall, the treatment according to protocol was at least 92%. At the Department of Surgery, University of Heidelberg, 307 patients were screened and 60 out of 130 eligible patients were randomized. There were no differences in demographic and clinical baseline data between included and non-included patients. In Erlangen, 351 patients were screened and 57 out of 106 eligible patients randomized. CONCLUSIONS: Results of the INSECT trial are applicable to a broad spectrum of patients treated at different hospital levels. PMID- 22316123 TI - Provision of oral health care to adult patients by dental therapists without the prescription of a dentist. AB - OBJECTIVES: Dental therapists are increasingly been seen as part of the solution to assist in improving access to dental care for underserved populations. The aim of this article is to report the outcomes of an educational bridging program designed to provide university-educated dental therapists with the appropriate knowledge and skills required to enable them to translate their current clinical scope of practice to adult patients aged 26+ years. METHODS: Ten dental therapists completed an educational program approved by the Dental Practice Board of Victoria as a pilot. Feedback from patients and supervising and supporting dentists was provided during the project. RESULTS: Supervising and supporting dentists rated the knowledge and clinical skills of participants as good to high at the completion of the education program and considered them safe to treat adults patients. Patients were very satisfied with the dental treatment provided. Eight participants successfully completed the assessment and were permitted by the Dental Practice Board of Victoria to extend their clinical scope of practice to adult patients. CONCLUSIONS: Feedback from patients and dentists indicated that, following the completion of an educational bridging program, dental therapists with a university education were able to develop the knowledge and skills required to treat adult patients aged 26+ years without the prescription or supervision of a dentist. Enabling dental therapists to treat adult patients may have a role to play in improving access to dental care for underserved populations. PMID- 22316124 TI - Model-based peak alignment of metabolomic profiling from comprehensive two dimensional gas chromatography mass spectrometry. AB - BACKGROUND: Comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GCxGC/TOF-MS) has been used for metabolite profiling in metabolomics. However, there is still much experimental variation to be controlled including both within-experiment and between-experiment variation. For efficient analysis, an ideal peak alignment method to deal with such variations is in great need. RESULTS: Using experimental data of a mixture of metabolite standards, we demonstrated that our method has better performance than other existing method which is not model-based. We then applied our method to the data generated from the plasma of a rat, which also demonstrates good performance of our model. CONCLUSIONS: We developed a model-based peak alignment method to process both homogeneous and heterogeneous experimental data. The unique feature of our method is the only model-based peak alignment method coupled with metabolite identification in an unified framework. Through the comparison with other existing method, we demonstrated that our method has better performance. Data are available at http://stage.louisville.edu/faculty/x0zhan17/software/software-development/mspa. The R source codes are available at http://www.biostat.iupui.edu/~ChangyuShen/CodesPeakAlignment.zip. TRIAL REGISTRATION: 2136949528613691. PMID- 22316126 TI - Mobile colloid generation induced by a cementitious plume: mineral surface-charge controls on mobilization. AB - Cementitious materials are increasingly used as engineered barriers and waste forms for radiological waste disposal. Yet their potential effect on mobile colloid generation is not well-known, especially as it may influence colloid facilitated contaminant transport. Whereas previous papers have studied the introduction of cement colloids into sediments, this study examined the influence of cement leachate chemistry on the mobilization of colloids from a subsurface sediment collected from the Savannah River Site, USA. A sharp mobile colloid plume formed with the introduction of a cement leachate simulant. Colloid concentrations decreased to background concentrations even though the aqueous chemical conditions (pH and ionic strength) remained unchanged. Mobile colloids were mainly goethite and to a lesser extent kaolinite. The released colloids had negative surface charges and the mean particle sizes ranged primarily from 200 to 470 nm. Inherent mineralogical electrostatic forces appeared to be the controlling colloid removal mechanism in this system. In the background pH of ~6.0, goethite had a positive surface charge, whereas quartz (the dominant mineral in the immobile sediment) and kaolinite had negative surface charges. Goethite acted as a cementing agent, holding kaolinite and itself onto the quartz surfaces due to the electrostatic attraction. Once the pH of the system was elevated, as in the cementitious high pH plume front, the goethite reversed to a negative charge, along with quartz and kaolinite, then goethite and kaolinite colloids were mobilized and a sharp spike in turbidity was observed. Simulating conditions away from the cementitious source, essentially no colloids were mobilized at 1:1000 dilution of the cement leachate or when the leachate pH was <= 8. Extreme alkaline pH environments of cementitious leachate may change mineral surface charges, temporarily promoting the formation of mobile colloids. PMID- 22316125 TI - EGFR ligands drive multipotential stromal cells to produce multiple growth factors and cytokines via early growth response-1. AB - Cell therapy with adult bone marrow multipotential stromal cells/mesenchymal stem cells (MSCs) presents a promising approach to promote wound healing and tissue regeneration. The strong paracrine capability of various growth factors and cytokines is a key mechanism of MSC-mediated wound healing and tissue regeneration, and the goal of this study is to understand the underlying mechanism that supports the strong paracrine machineries in MSCs. Microarray database analyses revealed that early growth response-1 (EGR1) is highly expressed in MSCs. Our previous studies showed that epidermal growth factor (EGF) treatment induces growth factor production in MSCs in vitro. Since EGF strongly upregulates EGR1, we hypothesized that EGF receptor (EGFR)-EGR1 signaling plays a pivotal role in MSC paracrine activity. EGF treatment upregulated the gene expression of growth factors and cytokines, including EGFR ligands in a protein kinase C (PKC)- and/or mitogen-activated protein kinase-extracellular-signal regulated kinase-dependent manner, and it was reversed by shRNA against EGR1. PKC activator phorbol 12-myristate 13-acetate enhanced EGFR tyrosyl phosphorylation and upregulated the gene expression of growth factors and cytokines in a heparin binding EGF-like growth factor (HBEGF) inhibitor CRM197 sensitive manner, indicating an involvement of autocrined HBEGF in the downstream of PKC signaling. Moreover, stimulation with growth factors and cytokines induced the expression of EGFR ligands, presumably via EGR1 upregulation. These data indicate EGR1 as a convergence point of multiple signaling pathways, which in turn augments the production of multiple growth factors and cytokines by enhancing the autocrine signaling with EGFR ligands. PMID- 22316127 TI - Structural characteristics of novel Ca-Mg orthosilicate and suborthosilicate glasses: results from 29Si and 17O NMR spectroscopy. AB - The structural characteristics of novel alkaline-earth suborthosilicate glasses along the compositional join (1 - x)(Ca(0.5)Mg(0.5)O) - xSiO(2) with 0.28 <= x <= 0.33 are investigated using high resolution (29)Si and (17)O nuclear magnetic resonance spectroscopy. The structures of these glasses consist of isolated Q(0) and Q(1) anionic species and Mg(2+) and Ca(2+) countercations that are held together by Coulombic interactions. The concentration of the Q(1) species rapidly decreases with decreasing SiO(2) content and becomes undetectable in the glass with x = 28 mol %. The compositional variation of the physical properties of these glasses such as glass transition temperature and density can be attributed to the Q-speciation in the structure. The NBOs are associated with a random distribution of the alkaline-earth cations in their nearest neighbor coordination shell. The resulting random packing of dissimilar Ca-NBO and Mg-NBO coordination polyhedra may give rise to structural and topological frustration responsible for the unusual glass-forming ability of these suborthosilicate liquids with extremely low SiO(2) contents. Finally, the composition and the formation of Q(1) species necessitate the formation of free O(2-) ions in the structure of these glasses that are only bonded to Mg(2+) and Ca(2+) cations. The (17)O NMR results presented in this study allow for direct observation of such oxygen species. PMID- 22316129 TI - Evolution of the eukaryotic ARP2/3 activators of the WASP family: WASP, WAVE, WASH, and WHAMM, and the proposed new family members WAWH and WAML. AB - BACKGROUND: WASP family proteins stimulate the actin-nucleating activity of the ARP2/3 complex. They include members of the well-known WASP and WAVE/Scar proteins, and the recently identified WASH and WHAMM proteins. WASP family proteins contain family specific N-terminal domains followed by proline-rich regions and C-terminal VCA domains that harbour the ARP2/3-activating regions. RESULTS: To reveal the evolution of ARP2/3 activation by WASP family proteins we performed a "holistic" analysis by manually assembling and annotating all homologs in most of the eukaryotic genomes available. We have identified two new families: the WAML proteins (WASP and MIM like), which combine the membrane deforming and actin bundling functions of the IMD domains with the ARP2/3 activating VCA regions, and the WAWH protein (WASP without WH1 domain) that have been identified in amoebae, Apusozoa, and the anole lizard. Surprisingly, with one exception we did not identify any alternative splice forms for WASP family proteins, which is in strong contrast to other actin-binding proteins like Ena/VASP, MIM, or NHS proteins that share domains with WASP proteins. CONCLUSIONS: Our analysis showed that the last common ancestor of the eukaryotes must have contained a homolog of WASP, WAVE, and WASH. Specific families have subsequently been lost in many taxa like the WASPs in plants, algae, Stramenopiles, and Euglenozoa, and the WASH proteins in fungi. The WHAMM proteins are metazoa specific and have most probably been invented by the Eumetazoa. The diversity of WASP family proteins has strongly been increased by many species- and taxon-specific gene duplications and multimerisations. All data is freely accessible via http://www.cymobase.org. PMID- 22316130 TI - Lower body functioning prevalence and correlates in older American Indians in a southeastern tribe: the Native Elder Care Study. AB - The objective of this study was to use performance-based measurements to identify, in a population of community-dwelling American Indians aged 55 and older, the prevalence and correlates of lower body functioning. Data were collected as part of a cross-sectional study of disability from members of a tribe in the southeast. Lower body functioning was measured using the Short Physical Performance Battery (SPPB), where higher scores reflect better functioning. Independent variables included age, sex, marital status, educational attainment, current cigarette smoking, physical activity, body mass index (BMI), hearing loss, vision loss, bone or joint trauma, chronic pain syndrome, osteoporosis, medical comorbidity, and depressive symptomatology. The total composite SPPB score (8.8 +/- 3.4) declined significantly with increasing age and was negatively associated with unmarried status, physical inactivity, vision loss, bone or joint trauma, and medical comorbidity after adjustment for all other factors in the model. Likewise, all individual SPPB component scores declined significantly with increasing age and were negatively associated with physical inactivity and comorbidity. The balance test score was significantly and negatively associated with unmarried status and vision loss; gait speed was negatively related to unmarried status; and chair stand test score was negatively related to BMI, vision loss, bone or joint trauma, and chronic pain syndrome. In the clinical setting, the SPPB can be an important screening tool for adverse health-related events. Further studies are needed to investigate the determinants and sequelae of physical dysfunction in this population. PMID- 22316131 TI - Patterning of magnetic bimetallic coordination nanoparticles of Prussian blue derivatives by the Langmuir-Blodgett technique. AB - We report a novel method to prepare patterns of nanoparticles over large areas of the substrate. This method is based on the adsorption of the negatively charged nanoparticles dispersed in an aqueous subphase onto a monolayer of the phospholipid dipalmitoyl-l-alpha-phosphatidylcholine (DPPC) at the air-water interface. It has been used to prepare patterns of nanoparticles of Prussian blue analogues (PBA) of different size (K(0.25)Ni[Fe(CN)(6)](0.75) (NiFe), K(0.25)Ni[Cr(CN)(6)](0.75) (NiCr), K(0.25)Ni[Co(CN)(6)](0.75) (NiCo), Cs(0.4)Co[Cr(CN)(6)](0.8) (CsCoCr), and Cs(0.4)Co[Fe(CN)(6)](0.9) (CsCoFe)). The behavior of DPPC monolayer at the air-water interface in the presence of the subphase of PBA nanoparticles has been studied by the compression isotherms and Brewster angle microscopy (BAM) images. Atomic force microscopy (AFM) of the transferred films on mica substrates shows that patterns of the nanoparticles are observed for a 10(-4) M concentration of the subphase, based on the nanoparticle precursors, at surface pressures between 1 and 6 mN/m and transfer velocities from 10 to 80 mm/min. Vertical, horizontal, or tilted fringes of the nanoparticles with respect to the transfer direction can be obtained depending on the transfer velocity and surface pressure. PMID- 22316132 TI - Superionic phase transition in silver chalcogenide nanocrystals realizing optimized thermoelectric performance. AB - Thermoelectric has long been recognized as a potentially transformative energy conversion technology due to its ability to convert heat directly into electricity. However, how to optimize the three interdependent thermoelectric parameters (i.e., electrical conductivity sigma, Seebeck coefficient S, and thermal conductivity kappa) for improving thermoelectric properties is still challenging. Here, we put forward for the first time the semiconductor-superionic conductor phase transition as a new and effective way to selectively optimize the thermoelectric power factor based on the modulation of the electric transport property across the phase transition. Ultra low value of thermal conductivity was successfully retained over the whole investigated temperature range through the reduction of grain size. As a result, taking monodisperse Ag(2)Se nanocrystals for an example, the maximized ZT value can be achieved around the temperature of phase transition. Furthermore, along with the effective scattering of short wavelength phonons by atomic defects created by alloying, the alloyed ternary silver chalcogenide compounds, monodisperse Ag(4)SeS nanocrystals, show better ZT value around phase transition temperature, which is cooperatively contributed by superionic phase transition and alloying at nanoscale. PMID- 22316133 TI - Disclosure of diagnosis by parents and caregivers to children infected with HIV: prevalence associated factors and perceived barriers in Addis Ababa, Ethiopia. AB - Vertical transmission of HIV from infected mothers to children is a common phenomenon. After the introduction of highly active antiretroviral treatment (HAART), most children live longer than before. Recently, HAART has become widely available to children living in sub-Saharan African countries, and this makes disclosure of HIV status an important issue. We conducted a cross-sectional survey involving 172 parents/caregivers of HIV-infected school-age children who had follow-up at the Pediatric Infectious Disease Clinic of the Yekatit 12 Hospital, Addis Ababa. Only 16.3% of HIV-infected schoolchildren knew their diagnosis. The child's age was the main predictor of disclosure (OR: -0.25; 95% CI: -0.35, -0.09; p<0.05). The main reason for nondisclosure was fear of negative emotional consequences for the child. More than half of the parent/caregivers agreed that they need to tell the children their diagnosis, but 86% reported that they needed health care providers to help them at the event. The low rate of disclosure found in this study shows the need for awareness creation and training of health professionals, and this should be supported by appropriate guidelines to be followed by health professionals working in pediatric ART clinics. Caregivers need to be provided with the necessary knowledge and skills on how to look after children who know their HIV status. PMID- 22316134 TI - Synthesis, molecular structure, conformational analysis, and chemical properties of silicon-containing derivatives of quinolizidine. AB - A silicon analog of quinolizidine 3,3,7,7-tetramethylhexahydro-1H [1,4,2]oxazasilino[4,5-d][1,4,2]oxazasilin-9a-yl)methanol 3 was synthesized. X ray diffraction analysis confirmed the trans configuration and low temperature NMR spectroscopy both the flexibility (barrier of interconversion 5.8 kcal mol( 1)) and the conformational equilibrium (chair-chair and chair-twist conformers) of the compound. The relative stability of the different isomers/conformers of 3 was calculated also at the MP2/6-311G(d,p) level of theory. Intra- and intermolecular hydrogen bonding in 3 and the appropriate equilibrium between free and self-associated molecules was studied in solvents of different polarity. Both the N-methyl quaternary ammonium salt and the O-trimethylsilyl derivative of 3 could be obtained and their structure determined. PMID- 22316135 TI - Inflammasome and caspase-1 inhibition caused by Bcl-2 and Bcl-XL may influence cytokine responses of lipopolysaccharide-stimulated peripheral blood mononuclear cells from septic patients. PMID- 22316137 TI - Mineralogical, geochemical and radiological characterisation of Selmo Formation in Batman area, Turkey. AB - This work deals with the mineralogical, geochemical and radiological characterisations of Selmo Formation in Batman neighbourhood. The upper Miocene Pliocene Selmo Formation is common in the centre of Batman and composed of carbonated sandy claystones and silty-sandy stone lenses. The common whole minerals of the samples are quartz, feldspars, calcite and dolomite. The clay minerals are smectite, illite, chlorite and mixed-layer clay (chlorite-smectite). The geochemical mean values of the samples are 51.7% SiO(2); 12.6% Al(2)O(3); 6.2% Fe(2)O(3); 3.6% MgO; 6.3% CaO; 1.1% Na(2)O; 1.7% K(2)O; 0.8% TiO(2); 0.2% P(2)O(5); 0.1% MnO; and 0.03% Cr(2)O(3). In addition, baseline maps for the concentrations of each radionuclide, the radium equivalent activity and the outdoor gamma dose rate distributions have been plotted for the study area. The mean activity concentrations of (226)Ra, (232)Th, (40)K and (137)Cs were determined to be 32, 24, 210 and 9 Bq kg(-1), respectively. The assessments of the radiological hazard indices, such as radium equivalent activity, absorbed dose rate in air, annual effective dose equivalent, excess lifetime cancer risk, external hazard index and internal hazard index, were calculated and compared with the internationally accepted reference values. This study shows that the concentrations of radioactivities in the measured samples were within the recommended safety limits and did not pose to be any significant source of radiation hazard. PMID- 22316136 TI - Halocarbocyclization entry into the oxabicyclo[4.3.1]decyl exomethylene-delta lactone cores of linearifolin and zaluzanin A: exploiting combinatorial catalysis. AB - A streamlined entry into the sesquiterpene lactone (SQL) cores of linearifolin and zaluzanin A is described. Stereochemistry is controlled through transformations uncovered by ISES (In Situ Enzymatic Screening). Absolute stereochemistry derives from kinetic resolution of 5-benzyloxypentene-1,2-oxide, utilizing a beta-pinene-derived-Co(III)-salen. Relative stereochemistry (1,3-cis fusion) is set via formal halometalation/carbocyclization, mediated by [Rh(O(2)CC(3)F(7))(2)](2)/LiBr. Subsequent ring-closing metathesis (RCM-Grubbs II) yields the title exomethylene-delta-lactone SQL cores. In complementary fashion, RCM with Grubbs-I catalyst provides the oxabicyclo[3.3.1]nonyl core of xerophilusin R and zinagrandinolide. PMID- 22316138 TI - Spt6 levels are modulated by PAAF1 and proteasome to regulate the HIV-1 LTR. AB - BACKGROUND: Tat-mediated activation of the HIV-1 promoter depends upon a proteasome-associated factor, PAAF1, which dissociates 26S proteasome to produce 19S RP that is essential for transcriptional elongation. The effect of PAAF1 on proteasome activity could also potentially shield certain factors from proteolysis, which may be implicated in the transcriptional co-activator activity of PAAF1 towards the LTR. RESULTS: Here, we show that Spt6 is targeted by proteasome in the absence of PAAF1. PAAF1 interacts with the N-terminus of Spt6, suggesting that PAAF1 protects Spt6 from proteolysis. Depletion of either PAAF1 or Spt6 reduced histone occupancy at the HIV-1 promoter, and induced the synthesis of aberrant transcripts. Ectopic Spt6 expression or treatment with proteasome inhibitor partially rescued the transcription defect associated with loss of PAAF1. Transcriptional profiling followed by ChIP identified a subset of cellular genes that are regulated in a similar fashion to HIV-1 by Spt6 and/or PAAF1, including many that are involved in cancer, such as BRCA1 and BARD1. CONCLUSION: These results show that intracellular levels of Spt6 are fine-tuned by PAAF1 and proteasome, which is required for HIV-1 transcription and extends to cellular genes implicated in cancer. PMID- 22316139 TI - Decomposing associations between acculturation and drinking in Mexican Americans. AB - BACKGROUND: Acculturation to life in the United States is a known predictor of Hispanic drinking behavior. We compare the ability of 2 theoretical models of this effect-sociocultural theory and general stress theory-to account for associations between acculturation and drinking in a sample of Mexican Americans. Limitations of previous evaluations of these theoretical models are addressed using a broader range of hypothesized cognitive mediators and a more direct measure of acculturative stress. In addition, we explore nonlinearities as possible underpinnings of attenuated acculturation effects among men. METHODS: Respondents (N = 2,595, current drinker N = 1,351) were interviewed as part of 2 recent multistage probability samples in a study of drinking behavior among Mexican Americans in the United States. The ability of norms, drinking motives, alcohol expectancies, and acculturation stress to account for relations between acculturation and drinking outcomes (volume and heavy drinking days) were assessed with a hierarchical linear regression strategy. Nonlinear trends were assessed by modeling quadratic effects of acculturation and acculturation stress on cognitive mediators and drinking outcomes. RESULTS: Consistent with previous findings, acculturation effects on drinking outcomes were stronger for women than men. Among women, only drinking motives explained acculturation associations with volume or heavy drinking days. Among men, acculturation was linked to increases in norms, and norms were positive predictors of drinking outcomes. However, adjusted effects of acculturation were nonexistent or trending in a negative direction, which counteracted this indirect normative influence. Acculturation stress did not explain the positive associations between acculturation and drinking. CONCLUSIONS: Stress and alcohol outcome expectancies play little role in the positive linear association between acculturation and drinking outcomes, but drinking motives appear to at least partially account for this effect. Consistent with recent reports, these results challenge stress models of linear acculturation effects on drinking outcomes and provide (partial) support for sociocultural models. Inconsistent mediation patterns-rather than nonlinearities represented a more plausible statistical description of why acculturation drinking associations are weakened among men. PMID- 22316140 TI - Molecular dynamics simulations of the TrkH membrane protein. AB - TrkH is a transmembrane protein that mediates uptake of K(+) through the cell membrane. Despite the recent determination of its crystallographic structure, the nature of the permeation mechanism is still unknown, that is, whether K(+) ions move across TrkH by active transport or passive diffusion. Here, molecular dynamics simulations and the umbrella sampling technique have been employed to shed light on this question. The existence of binding site S3 and two alternative binding sites have been characterized. Analysis of the coordination number renders values that are almost constant, with a full contribution from the carbonyls of the protein only at S3. This observation contrasts with observations of K(+) channels, where the contribution of the protein to the coordination number is roughly constant in all four binding sites. An intramembrane loop is found immediately after the selectivity filter at the intracellular side of the protein, which obstructs the permeation pathway, and this is reflected in the magnitude of the energy barriers. PMID- 22316141 TI - An intervention to increase caregiver support for asthma management in middle school-aged youth. AB - OBJECTIVE: Asthma control requires adherence to a treatment regimen. Caregiver involvement is a key determinant of adolescent asthma control, but the involvement must recognize the youth's developmental stage and need for autonomy. This article describes the evaluation of a pilot asthma management intervention for middle school-aged youth and their adult network members, including caregivers, based on caregiver findings. METHODS: Following approval from San Diego State University's Institutional Review Board and school district authorization, two middle schools were randomized into one of two conditions: 6 weekly group-based skills training for the adolescents followed by 6-weekly targeted newsletters for caregivers and others (Group 1) versus group-based skills training for adolescents only (Group 2). Outcome evaluation examined pre post changes by study condition. RESULTS: Caregivers in both groups reported improvements in quality of life (QOL) and access to asthma care resources among their adolescents. Caregiver self-efficacy increased significantly among Group 1 versus Group 2 caregivers, while Group 2 caregivers (those who did not receive newsletters) reported that their adolescents had more responsibility for their asthma care compared with Group 2 caregivers. CONCLUSIONS: The adolescent-only intervention resulted in improvements in caregivers' QOL and parenting behaviors that promoted the adolescent's access to asthma resources. When caregivers were directed with intervention materials, their self-efficacy increased. Those who did not receive materials reported that their adolescents had more responsibility for their asthma care. The latter finding may reflect an unintended consequence of an adolescent-only intervention as it may communicate to caregivers to assume less responsibility for their child's asthma care. PMID- 22316142 TI - Suboptimal reporting of adverse medical events to the FDA Adverse Events Reporting System by nurse practitioners and physician assistants. AB - OBJECTIVES: The Adverse Events Reporting System (AERS) of the FDA is used to identify toxicities of drugs that are on the market. Nurse practitioners (NP) and physician assistants (PA), having an increasing role in the delivery of medical care, are also needed to participate in post-marketing pharmacovigilance. This study was performed to assess awareness and use of the AERS in voluntary reporting of drug toxicities by NPs and PAs. METHODS: A cluster sample survey was issued at the Principles of Gastroenterology for the Nurse Practitioner and Physician Assistant course in August 2010. The survey assessed familiarity with the AERS, the number of adverse events seen and the frequency of reports sent to the AERS. NP and PA responses were compared using the two-tailed Fisher's exact. RESULTS: Of the 92 respondents, 67 (72%) were NPs and 24 (26%) PAs. Of the 50 (54%) respondents that reported being familiar with the AERS system, 20 (40%) incorrectly identified the methods to report using the AERS. Overall reporting of adverse events was low, particularly in respondents seeing 5-12 adverse events per year. CONCLUSION: The study suggests that improved education regarding the importance of using AERS for pharmacovigilance is suggested for NPs and PAs. Due to the small size of the study, these data should be viewed as preliminary, pending a larger confirmatory study. PMID- 22316143 TI - Group A Streptococcus causing descending necrotizing mediastinitis: report of a case and literature review. AB - BACKGROUND: Descending necrotizing mediastinitis is a serious condition with few cases reported in the literature. Surgical treatment is controversial and may include wound exploration, local drainage, and even mediastinal debridement approached by thoracotomy. METHODS: Description of a case of descending mediastinitis caused by group A Streptococcus as a complication of thyroidectomy. RESULTS: Aggressive debridement was required for source control and treatment of septic shock. CONCLUSION: Post-thyroidectomy descending necrotizing mediastinitis is a rare and dangerous infection. It should be treated aggressively with appropriate cervical and mediastinal drainage combined with optimum medical care. PMID- 22316144 TI - Pharmacokinetics of beta-lactam antibiotics in patients with intra-abdominal disease: a structured review. AB - BACKGROUND AND PURPOSE: The objective of this structured review was to analyze critically the findings of pharmacokinetic studies of beta-lactam antibiotics in patients with intra-abdominal disease; that is, intra-abdominal infection (IAI) or previous abdominal surgery and determine the requirements for dosage modification in this population. METHODS: Data were identified by structured review of PUBMED from February 1983 to February 2011. All 14 articles reviewed described the pharmacokinetics of beta-lactam antibiotics in patients with intra abdominal disease. RESULTS: Antibiotic classes included carbapenems, penicillins, cephalosporins, and monobactams. Possible physiological changes in these patients include development of abscesses, perforation, or ischemia of the bowel as well as intra-abdominal hypertension. These disorders may cause changes in antibiotic pharmacokinetics, including increased volume of distribution and faster drug clearance, both resulting in lower antibiotic concentrations. High inter individual pharmacokinetic variability was common to each of the studies. CONCLUSION: Most of the available data demonstrate that drug volume of distribution can be increased significantly in the presence of intra-abdominal disease. Drug clearance is likely to vary in line with renal or hepatic function. Thus, dose optimization is important to prevent development of antibiotic resistance or therapeutic failure. However, further research is necessary to determine the clinical outcome of individualized dosing on the basis of pharmacokinetic/pharmacodynamic studies. PMID- 22316145 TI - Cefazolin dosing for surgical prophylaxis in morbidly obese patients. AB - BACKGROUND: Cefazolin is used commonly to prevent surgical site infection (SSI) after operations on patients with morbid obesity (MO), but specific dosing guidelines are lacking. We hypothesized that cefazolin 2 g given by intravenous (IV) push over 5 min (IVP) or infusion over 30 min (INF) would suffice for SSI prophylaxis in MO (body mass index [BMI] 40-50 kg/m(2)), and cefazolin 3 g would be sufficient in patients with super-morbid obesity (SMO) (BMI >50 kg/m(2)). METHODS: Twenty-five patients undergoing elective surgical procedures were given a single dose of cefazolin: Ten with MO received 2 g via IVP (MO2-IVP), five with MO received 2 g via 30-min infusion (MO2-INF), five with SMO received 2 g via infusion (SMO2-INF), and five with SMO received 3 g via infusion (SMO3-INF). Serum cefazolin concentrations were measured 5, 30, 120, and 360 min after initiation of the dose. The half-life of the drug was calculated for each patient, as was the time the concentration was above the minimum inhibitory free concentration (fT>MIC) using 8 mcg/mL as the breakpoint. The protective duration of each cefazolin dose was assessed using the pharmacodynamic target for fT>MIC of 70%. RESULTS: The mean cefazolin concentrations after 30 min were similar in all groups; the mean concentrations at 120 and 360 min were 67.1-84.8 mcg/mL and 22.9-40.8 mcg/mL, respectively. The half-life ranged from 2.3 to 3.6 h and was unaffected by administration method. The protective duration was 5.1 h for MO2 IVP, 4.8 h for MO2-INF, 5.8 h for SMO2-INF, and 6.8 h for SMO3-INF. CONCLUSIONS: A single 2-g dose of cefazolin appears to provide antibiotic exposures sufficient for most common general surgical procedures of <5-h duration, regardless of BMI. PMID- 22316146 TI - Treatment of severe hemolytic anemia caused by Clostridium perfringens sepsis in a liver transplant recipient. AB - BACKGROUND: Clostridium perfringens bacteremia accompanied by extensive intravascular hemolysis is an almost inescapably fatal infection. METHODS: Case report and literature review. RESULTS: A 52-year-old man with a recent history of liver transplantation developed sepsis and severe hemolytic anemia. The patient had multiple organ dysfunction syndrome and required aggressive transfusion, antibiotics, and continuous hemodialysis. Blood cultures grew C. perfringens. With appropriate resuscitation and antibiotic treatment, the patient had a complete, although complicated recovery. CONCLUSION: This is the first reported case of a liver transplant patient developing fulminant C. perfringens sepsis with hemolysis. This infection usually kills patients within hours of presentation. Early recognition and aggressive treatment is necessary to avoid this outcome. PMID- 22316147 TI - Patients' attitudes toward screening for medical conditions in a dental setting. AB - OBJECTIVES: Previous studies demonstrated the efficacy of chairside medical screening by dentists to identify patients who are at increased risk for developing cardiovascular-associated events and the favorable attitude of dentists toward chairside medical screening. This study assessed patient attitudes toward chairside medical screening in a dental setting. METHODS: A self administered questionnaire of eight five-point response scale questions was given to a convenience sample of adult patients attending an inner-city dental school clinic and two private practice settings. Wilcoxon-Mann-Whitney tests and t-tests were used to compare responses between study groups. Friedman nonparametric analysis of variance was used to compare response items within each question. RESULTS: Regardless of setting, the majority of respondents was willing to have a dentist conduct screening for heart disease, high blood pressure, diabetes, human immunodeficiency virus infection, and hepatitis infection (55-90 percent); discuss results immediately (79 percent and 89 percent); provide oral fluids, finger-stick blood, blood pressure measurements, and height and weight (60-94 percent); and pay up to $20 (50-67 percent). Respondents reported that their opinion of the dentist would improve regarding the dentist's professionalism, knowledge, competence, and compassion (48-77 percent). The fact that the test was not done by a physician was ranked as the least important potential barrier. While all respondents expressed a favorable attitude toward chairside screening, the mean score was significantly lower among clinic patients across most questions/items. The priority rankings within an item were similar for both groups. CONCLUSIONS: Acceptance by patients of chairside medical screening in a dental setting is a critical element for successful implementation of this strategy. PMID- 22316148 TI - Does pre-exercise static stretching inhibit maximal muscular performance? A meta analytical review. AB - We applied a meta-analytical approach to derive a robust estimate of the acute effects of pre-exercise static stretching (SS) on strength, power, and explosive muscular performance. A computerized search of articles published between 1966 and December 2010 was performed using PubMed, SCOPUS, and Web of Science databases. A total of 104 studies yielding 61 data points for strength, 12 data points for power, and 57 data points for explosive performance met our inclusion criteria. The pooled estimate of the acute effects of SS on strength, power, and explosive performance, expressed in standardized units as well as in percentages, were -0.10 [95% confidence interval (CI): -0.15 to -0.04], -0.04 (95% CI: -0.16 to 0.08), and -0.03 (95% CI: -0.07 to 0.01), or -5.4% (95% CI: -6.6% to -4.2%), 1.9% (95% CI: -4.0% to 0.2%), and -2.0% (95% CI: -2.8% to -1.3%). These effects were not related to subject's age, gender, or fitness level; however, they were more pronounced in isometric vs dynamic tests, and were related to the total duration of stretch, with the smallest negative acute effects being observed with stretch duration of <= 45 s. We conclude that the usage of SS as the sole activity during warm-up routine should generally be avoided. PMID- 22316149 TI - In silico lead identification and optimization for drug discovery. PMID- 22316151 TI - Computational drug design targeting protein-protein interactions. AB - Novel discoveries in molecular disease pathways within the cell, combined with increasing information regarding protein binding partners has lead to a new approach in drug discovery. There is interest in designing drugs to modulate protein-protein interactions as opposed to solely targeting the catalytic active site within a single enzyme or protein. There are many challenges in this new approach to drug discovery, particularly since the protein-protein interface has a larger surface area, can comprise a discontinuous epitope, and is more amorphous and less well defined than the typical drug design target, a small contained enzyme-binding pocket. Computational methods to predict modes of protein-protein interaction, as well as protein interface hot spots, have garnered significant interest, in order to facilitate the development of drugs to successfully disrupt and inhibit protein-protein interactions. This review summarizes some current methods available for computational protein-protein docking, as well as tabulating some examples of the successful design of antagonists and small molecule inhibitors for protein-protein interactions. Several of these drugs are now beginning to appear in the clinic. PMID- 22316150 TI - Identification of HIV inhibitors guided by free energy perturbation calculations. AB - Free energy perturbation (FEP) theory coupled to molecular dynamics (MD) or Monte Carlo (MC) statistical mechanics offers a theoretically precise method for determining the free energy differences of related biological inhibitors. Traditionally requiring extensive computational resources and expertise, it is only recently that its impact is being felt in drug discovery. A review of computer-aided anti-HIV efforts employing FEP calculations is provided here that describes early and recent successes in the design of human immunodeficiency virus type 1 (HIV-1) protease and non-nucleoside reverse transcriptase inhibitors. In addition, our ongoing work developing and optimizing leads for small molecule inhibitors of cyclophilin A (CypA) is highlighted as an update on the current capabilities of the field. CypA has been shown to aid HIV-1 replication by catalyzing the cis/trans isomerization of a conserved Gly-Pro motif in the Nterminal domain of HIV-1 capsid (CA) protein. In the absence of a functional CypA, e.g., by the addition of an inhibitor such as cyclosporine A (CsA), HIV-1 has reduced infectivity. Our simulations of acylurea-based and 1 indanylketone-based CypA inhibitors have determined that their nanomolar and micromolar binding affinities, respectively, are tied to their ability to stabilize Arg55 and Asn102. A structurally novel 1-(2,6-dichlorobenzamido) indole core was proposed to maximize these interactions. FEP-guided optimization, experimental synthesis, and biological testing of lead compounds for toxicity and inhibition of wild-type HIV-1 and CA mutants have demonstrated a dose-dependent inhibition of HIV-1 infection in two cell lines. While the inhibition is modest compared to CsA, the results are encouraging. PMID- 22316153 TI - The challenges involved in modeling toxicity data in silico: a review. AB - The percentage of failures in late pharmaceutical development due to toxicity has increased dramatically over the last decade or so, resulting in increased demand for new methods to rapidly and reliably predict the toxicity of compounds. In this review we discuss the challenges involved in both the building of in silico models on toxicology endpoints and their practical use in decision making. In particular, we will reflect upon the predictive strength of a number of different in silico models for a range of different endpoints, different approaches used to generate the models or rules, and limitations of the methods and the data used in model generation. Given that there exists no unique definition of a 'good' model, we will furthermore highlight the need to balance model complexity/interpretability with predictability, particularly in light of OECD/REACH guidelines. Special emphasis is put on the data and methods used to generate the in silico toxicology models, and their strengths and weaknesses are discussed. Switching to the applied side, we next review a number of toxicity endpoints, discussing the methods available to predict them and their general level of predictability (which very much depends on the endpoint considered). We conclude that, while in silico toxicology is a valuable tool to drug discovery scientists, much still needs to be done to, firstly, understand more completely the biological mechanisms for toxicity and, secondly, to generate more rapid in vitro models to screen compounds. With this biological understanding, and additional data available, our ability to generate more predictive in silico models should significantly improve in the future. PMID- 22316154 TI - Computational prediction of protein hot spot residues. AB - Most biological processes involve multiple proteins interacting with each other. It has been recently discovered that certain residues in these protein-protein interactions, which are called hot spots, contribute more significantly to binding affinity than others. Hot spot residues have unique and diverse energetic properties that make them challenging yet important targets in the modulation of protein-protein complexes. Design of therapeutic agents that interact with hot spot residues has proven to be a valid methodology in disrupting unwanted protein protein interactions. Using biological methods to determine which residues are hot spots can be costly and time consuming. Recent advances in computational approaches to predict hot spots have incorporated a myriad of features, and have shown increasing predictive successes. Here we review the state of knowledge around protein-protein interactions, hot spots, and give an overview of multiple in silico prediction techniques of hot spot residues. PMID- 22316155 TI - The different ways through which specificity works in orthosteric and allosteric drugs. AB - Currently, there are two types of drugs on the market: orthosteric, which bind at the active site; and allosteric, which bind elsewhere on the protein surface, and allosterically change the conformation of the protein binding site. In this perspective we argue that the different mechanisms through which the two drug types affect protein activity and their potential pitfalls call for different considerations in drug design. The key problem facing orthosteric drugs is side effects which can occur by drug binding to homologous proteins sharing a similar binding site. Hence, orthosteric drugs should have very high affinity to the target; this would allow a low dosage to selectively achieve the goal of target only binding. By contrast, allosteric drugs work by shifting the free energy landscape. Their binding to the protein surface perturbs the protein surface atoms, and the perturbation propagates like waves, finally reaching the binding site. Effective drugs should have atoms in good contact with the 'right' protein atoms; that is, the contacts should elicit propagation waves optimally reaching the protein binding site target. While affinity is important, the design should consider the protein conformational ensemble and the preferred propagation states. We provide examples from functional in vivo scenarios for both types of cases, and suggest how high potency can be achieved in allosteric drug development. PMID- 22316152 TI - From laptop to benchtop to bedside: structure-based drug design on protein targets. AB - As an important aspect of computer-aided drug design, structure-based drug design brought a new horizon to pharmaceutical development. This in silico method permeates all aspects of drug discovery today, including lead identification, lead optimization, ADMET prediction and drug repurposing. Structure-based drug design has resulted in fruitful successes drug discovery targeting proteinligand and protein-protein interactions. Meanwhile, challenges, noted by low accuracy and combinatoric issues, may also cause failures. In this review, state-of-the art techniques for protein modeling (e.g. structure prediction, modeling protein flexibility, etc.), hit identification/ optimization (e.g. molecular docking, focused library design, fragment-based design, molecular dynamic, etc.), and polypharmacology design will be discussed. We will explore how structure-based techniques can facilitate the drug discovery process and interplay with other experimental approaches. PMID- 22316157 TI - Multi-parameter optimization: identifying high quality compounds with a balance of properties. AB - A successful, efficacious and safe drug must have a balance of properties, including potency against its intended target, appropriate absorption, distribution, metabolism, and elimination (ADME) properties and an acceptable safety profile. Achieving this balance of, often conflicting, requirements is a major challenge in drug discovery. Approaches to simultaneously optimizing many factors in a design are broadly described under the term 'multi-parameter optimization' (MPO). In this review, we will describe how MPO can be applied to efficiently design and select high quality compounds and describe the range of methods that have been employed in drug discovery, including; simple 'rules of thumb' such as Lipinski's rule; desirability functions; Pareto optimization; and probabilistic approaches that take into consideration the uncertainty in all drug discovery data due to predictive error and experimental variability. We will explore how these methods have been applied to predicted and experimental data to reduce attrition and improve the productivity of the drug discovery process. PMID- 22316156 TI - Computational insights for the discovery of non-ATP competitive inhibitors of MAP kinases. AB - Due to their role in cellular signaling mitogen activated protein (MAP) kinases represent targets of pharmaceutical interest. However, the majority of known MAP kinase inhibitors compete with cellular ATP and target an ATP binding pocket that is highly conserved in the 500 plus representatives of the human protein kinase family. Here we review progress toward the development of non-ATP competitive MAP kinase inhibitors for the extracellular signal regulated kinases (ERK1/2), the c jun N-terminal kinases (JNK1/2/3) and the p38 MAPKs (alpha, beta, gamma, and delta). Special emphasis is placed on the role of computational methods in the drug discovery process for MAP kinases. Topics include recent advances in X-ray crystallography theory that improve the MAP kinase structures essential to structurebased drug discovery, the use of molecular dynamics to understand the conformational heterogeneity of the activation loop and inhibitors discovered by virtual screening. The impact of an advanced polarizable force field such as AMOEBA used in conjunction with sophisticated kinetic and thermodynamic simulation methods is also discussed. PMID- 22316158 TI - Cis-enone resorcylic acid lactones (RALs) as irreversible protein kinase inhibitors. AB - Resorcylic acid lactones (RALs) constitute a group of polyketide natural products with a large macrocyclic ring fused to resorcylic acid. Despite distinct core scaffold from all marketed kinase inhibitors, RALs bearing a cis-enone moiety have recently shown irreversible yet selective inhibition on a subset of kinases along the MAPK signaling pathway such as MEK, ERK and TAK1. The biochemical and structural studies have demonstrated that the cis-enone RALs can inhibit kinase activity by forming a covalent Michael adduct with an adequately positioned cysteine residue in the ATP binding pocket. This review discusses the mechanism of action, synthetic strategies, and structure-activity relationships (SARs) of cis-enone RALs. It is anticipated that design, synthesis and evaluation of cis enone RALs analogs will diversify the chemical space of kinase inhibitors and facilitate the development of new leads for the treatment of various diseases such as cancer and inflammatory disorders. PMID- 22316159 TI - Conformational transition and energy landscape of ErbB4 activated by neuregulin1beta: one microsecond molecular dynamics simulations. AB - ErbB4, a receptor tyrosine kinase of the ErbB family, plays crucial roles in cell growth and differentiation, especially in the development of the heart and nervous system. Ligand binding to its extracellular region could modulate the activation process. To understand the mechanism of ErbB4 activation induced by ligand binding, we performed one microsecond molecular dynamics (MD) simulations on the ErbB4 extracellular region (ECR) with and without its endogenous ligand neuregulin1beta (NRG1beta). The conformational transition of the ECR ErbB4/NRG1beta complex from a tethered inactive conformation to an extended active-like form has been observed, while such large and function-related conformational change has not been seen in the simulation on the ECR-ErbB4, suggesting that ligand binding is indeed the active inducing force for the conformational transition and further dimerization. On the basis of MD simulations and principal component analysis, we constructed a rough energy landscape for the conformational transition of ECR-ErbB4/NRG1beta complex, suggesting that the conformational change from the inactive state to active-like state involves a stable conformation. The energy barrier for the tether opening was estimated as ~2.7 kcal/mol, which is very close to the experimental value (1 2 kcal/mol) reported for ErbB1. On the basis of the simulation results, an atomic mechanism for the ligand-induced activation of ErbB4 was postulated. The present MD simulations provide a new insight into the conformational changes underlying the activation of ErbB4. PMID- 22316160 TI - Seroprevalence of Ehrlichia canis, Ehrlichia chaffeensis and Ehrlichia ewingii in dogs in North America. AB - BACKGROUND: This study evaluated the exposure of dogs to three different Ehrlichia spp. in the south and central regions of the United States where vector borne disease prevalence has been previously difficult to ascertain, particularly beyond the metropolitan areas. METHODS: Dog blood samples (n = 8,662) were submitted from 14 veterinary colleges, 6 private veterinary practices and 4 diagnostic laboratories across this region. Samples were tested for E. canis, E. chaffeensis and E. ewingii specific antibodies using peptide microtiter ELISAs. RESULTS: Overall, E. canis, E. chaffeensis and E. ewingii seroprevalence was 0.8%, 2.8%, and 5.1%, respectively. The highest E. canis seroprevalence (2.3%) was found in a region encompassing Arkansas, Louisiana, Oklahoma, Tennessee and Texas. E. chaffeensis seroreactivity was 6.6% in the central region (Arkansas, Kansas, Missouri, and Oklahoma) and 4.6% in the southeast region (Georgia, Maryland, North Carolina, South Carolina, Tennessee and Virginia). Seroreactivity to E. ewingii was also highest in the central region (14.6%) followed by the southeast region (5.9%). The geospatial pattern derived from E. chaffeensis and E. ewingii seropositive samples was similar to previous reports based on E. chaffeensis seroreactivity in white-tailed deer and the distribution of human monocytic ehrlichiosis (HME) cases reported by the CDC. CONCLUSIONS: The results of this study provide the first large scale regional documentation of exposure to E. canis, E. chaffeensis and E. ewingii in pet dogs, highlighting regional differences in seroprevalence and providing the basis for heightened awareness of these emerging vector-borne pathogens by veterinarians and public health agencies. PMID- 22316161 TI - Armed and accurate: engineering cytotoxic T cells for eradication of leukemia. AB - Translational medicine depends on a rapid and efficient exchange of results between the bench and the bedside. A recent example from the field of cancer immunotherapy highlights the essential nature of this exchange. Methods have been developed to convert a patient's cytotoxic T cells into efficient and specific killers of cancer cells in patients with leukemia. By using recombinant DNA techniques, a lentiviral vector was constructed to express chimeric antigen receptors in cytotoxic T cells from patients with advanced chronic lymphocytic leukemia. The purpose of the chimeric receptors was to direct the cytotoxic T cell activity against cells causing the cancer. The effect of infusing the engineered T cells back into the cancer patients was tested in a Phase I trial at the University of Pennsylvania, and the initial results were described in two articles from the research team of Dr. Carl June. The remarkable success of this trial should energize further applications of biotechnology in the development of new cancer immunotherapies. PMID- 22316162 TI - Frailty transitions in the San Antonio Longitudinal Study of Aging. AB - OBJECTIVES: To examine frailty transitions in Mexican American (MA) and European American (EA) older adults. DESIGN: Longitudinal, observational cohort study. SETTING: Socioeconomically diverse neighborhoods in San Antonio, Texas. PARTICIPANTS: Three hundred twelve MA and 285 EA community-dwelling older adults (>= 65) with frailty information at baseline (1992-1996) and transition information at follow-up (2000/01) in the San Antonio Longitudinal Study of Aging. MEASUREMENTS: Five frailty characteristics (weight loss, exhaustion, weakness, slowness, and low physical activity), frailty score (0-5), and overall frailty state (nonfrail = 0 characteristics, prefrail = 1 or 2, frail = >= 3) were assessed at baseline. Transitions (progressed, regressed, or no change) were assessed for frailty score and state. Odds ratios (ORs) of progression and regression in individual characteristics were estimated using generalized estimating equations adjusted for age, sex, ethnic group, socioeconomic status, comorbidity, diabetes, and follow-up interval. RESULTS: Diabetes mellitus with macrovascular complications (OR = 1.84, 95% confidence interval (CI) = 1.02 3.33), fewer years of education (OR = 0.96, 95% CI = 0.93-1.0) and follow-up interval (OR = 1.3, 95% CI = 1.17-1.46) were significant predictors of progression in any frailty characteristic. Mortality increased with greater frailty state, and prefrail individuals were more likely than frail individuals to regress. CONCLUSION: Diabetes mellitus with macrovascular complications and fewer years of education are important predictors of progression in any frailty characteristic. Because of greater risk of death than for the nonfrail state and greater likelihood of regression than for the frail state, the prefrail state may be an optimal target for intervention. PMID- 22316163 TI - Evolution of the intercontinental disjunctions in six continents in the Ampelopsis clade of the grape family (Vitaceae). AB - BACKGROUND: The Ampelopsis clade (Ampelopsis and its close allies) of the grape family Vitaceae contains ca. 43 species disjunctly distributed in Asia, Europe, North America, South America, Africa, and Australia, and is a rare example to study both the Northern and the Southern Hemisphere intercontinental disjunctions. We reconstruct the temporal and spatial diversification of the Ampelopsis clade to explore the evolutionary processes that have resulted in their intercontinental disjunctions in six continents. RESULTS: The Bayesian molecular clock dating and the likelihood ancestral area analyses suggest that the Ampelopsis clade most likely originated in North America with its crown group dated at 41.2 Ma (95% HPD 23.4-61.0 Ma) in the middle Eocene. Two independent Laurasian migrations into Eurasia are inferred to have occurred in the early Miocene via the North Atlantic land bridges. The ancestor of the Southern Hemisphere lineage migrated from North America to South America in the early Oligocene. The Gondwanan-like pattern of intercontinental disjunction is best explained by two long-distance dispersals: once from South America to Africa estimated at 30.5 Ma (95% HPD 16.9-45.9 Ma), and the other from South America to Australia dated to 19.2 Ma (95% HPD 6.7-22.3 Ma). CONCLUSIONS: The global disjunctions in the Ampelopsis clade are best explained by a diversification model of North American origin, two Laurasian migrations, one migration into South America, and two post-Gondwanan long-distance dispersals. These findings highlight the importance of both vicariance and long distance dispersal in shaping intercontinental disjunctions of flowering plants. PMID- 22316164 TI - Hydration of calcium oxide surface predicted by reactive force field molecular dynamics. AB - In this work, we present the parametrization of Ca-O/H interactions within the reactive force field ReaxFF, and its application to study the hydration of calcium oxide surface. The force field has been fitted using density functional theory calculations on gas phase calcium-water clusters, calcium oxide bulk and surface properties, calcium hydroxide, bcc and fcc Ca, and proton transfer reactions in the presence of calcium. Then, the reactive force field has been used to study the hydration of the calcium oxide {001} surface with different water contents. Calcium oxide is used as a catalyzer in many applications such as CO(2) sequestration and biodiesel production, and the degree of surface hydroxylation is a key factor in its catalytic performance. The results show that the water dissociates very fast on CaO {001} bare surfaces without any defect or vacancy. The surface structure is maintained up to a certain amount of water, after which the surface undergoes a structural rearrangement, becoming a disordered calcium hydroxyl layer. This transformation is the most probable reason for the CaO catalytic activity decrease. PMID- 22316165 TI - The nitric oxide pathway--evidence and mechanisms for protection against liver ischaemia reperfusion injury. AB - Ischaemia reperfusion (IR) injury is a clinical entity with a major contribution to the morbidity and mortality of liver surgery and transplantation. A central pathway of protection against IR injury utilizes nitric oxide (NO). Nitric oxide synthase (NOS) enzymes manufacture NO from L-arginine. NO generated by the endothelial NOS (eNOS) isoform protects against liver IR injury, whereas inducible NOS (iNOS)-derived NO may have either a protective or a deleterious effect during the early phase of IR injury, depending on the length of ischaemia, length of reperfusion and experimental model. In late phase hepatic IR injury, iNOS-derived NO plays a protective role. In addition to NOS consumption of L arginine during NO synthesis, this amino acid may also be metabolized by arginase, an enzyme whose release is increased during prolonged ischaemia, and therefore diverts L-arginine away from NOS metabolism leading to a drop in the rate of NO synthesis. NO most commonly acts through the soluble guanylyl cyclase cyclic GMP- protein kinase G pathway to ameliorate hepatic IR injury. Both endogenously generated and exogenously administered NO donors protect against liver IR injury. The beneficial effects of NO on liver IR are not, however, universal, and certain conditions, such as steatosis, may influence the protective effects of NO. In this review, the evidence for, and mechanisms of these protective actions of NO are discussed, and areas in need of further research are highlighted. PMID- 22316166 TI - Diastereoselective synthesis of substituted tetrahydrothiopyrans via (3,5) thionium-ene cyclization reaction. AB - Tetrahydrothiopyrans have been efficiently synthesized in good yields with excellent diastereoselectivity from aldehydes and substituted 5-methylhex-4-ene-1 thiol via (3,5)-thionium-ene cyclization reaction mediated by boron trifluoride etherate. PMID- 22316167 TI - Cell phone based balance trainer. AB - BACKGROUND: In their current laboratory-based form, existing vibrotactile sensory augmentation technologies that provide cues of body motion are impractical for home-based rehabilitation use due to their size, weight, complexity, calibration procedures, cost, and fragility. METHODS: We have designed and developed a cell phone based vibrotactile feedback system for potential use in balance rehabilitation training in clinical and home environments. It comprises an iPhone with an embedded tri-axial linear accelerometer, custom software to estimate body tilt, a "tactor bud" accessory that plugs into the headphone jack to provide vibrotactile cues of body tilt, and a battery. Five young healthy subjects (24 +/ 2.8 yrs, 3 females and 2 males) and four subjects with vestibular deficits (42.25 +/- 13.5 yrs, 2 females and 2 males) participated in a proof-of-concept study to evaluate the effectiveness of the system. Healthy subjects used the system with eyes closed during Romberg, semi-tandem Romberg, and tandem Romberg stances. Subjects with vestibular deficits used the system with both eyes-open and eyes-closed conditions during semi-tandem Romberg stance. Vibrotactile feedback was provided when the subject exceeded either an anterior-posterior (A/P) or a medial-lateral (M/L) body tilt threshold. Subjects were instructed to move away from the vibration. RESULTS: The system was capable of providing real time vibrotactile cues that informed corrective postural responses. When feedback was available, both healthy subjects and those with vestibular deficits significantly reduced their A/P or M/L RMS sway (depending on the direction of feedback), had significantly smaller elliptical area fits to their sway trajectory, spent a significantly greater mean percentage time within the no feedback zone, and showed a significantly greater A/P or M/L mean power frequency. CONCLUSION: The results suggest that the real-time feedback provided by this system can be used to reduce body sway. Its advantages over more complex laboratory-based and commercial balance training systems in terms of cost, size, weight, functionality, flexibility, and accessibility make it a good candidate for further home-based balance training evaluation. PMID- 22316168 TI - Cytotoxic cardiac glycosides and other compounds from Asclepias syriaca. AB - Phytochemical investigation of the dried biomass of Asclepias syriaca afforded five new compounds (1-5), along with 19 known structures. Overall, the secondary metabolites isolated and identified from this plant showed a wide structural diversity including pentacyclic triterpenes, cardiac glycosides, flavonoid glycosides, lignans, a phenylethanoid, and a glycosylated megastigmane. In addition, the isolates were tested against the cancer breast cell line Hs578T, and those showing IC(50) values lower than 50 MUM (1 and 6-9) were further investigated in three additional breast cancer cell lines (MCF-7, T47D, and Sk-Br 3) and the normal breast cell line Hs578Bst. PMID- 22316169 TI - Lung recruitment in ARDS: we are still confused, but on a higher PEEP level. AB - Recruitment maneuvers and the application of high levels of positive end expiratory pressure combined with lung protective mechanical ventilation strategies have been proposed to improve pulmonary function in patients with severe acute respiratory distress syndrome. However, the optimal way to achieve and maintain alveolar recruitment is still under debate. PMID- 22316170 TI - Benzo[a]pyrene-induced changes in microRNA-mRNA networks. AB - Toxicological studies assessing the safety of compounds for humans frequently use in vitro systems to characterize toxic responses in combination with transcriptomic analyses. Thus far, changes have mostly been investigated at the mRNA level. Recently, microRNAs have attracted attention because they are powerful negative regulators of mRNA levels and, thus, may be responsible for the modulation of important mRNA networks implicated in toxicity. This study aimed to identify possible microRNA-mRNA networks as novel interactions on the gene expression level after a genotoxic insult. We used benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon, as a model genotoxic/carcinogenic compound. We analyzed time-dependent effects on mRNA and microRNA profiles in HepG2 cells, a widely used human liver cell line that expresses active p53 and is competent for the biotransformation of BaP. Changes in microRNA expression in response to BaP, in combination with multiple alterations of mRNA levels, were observed. Many of these altered mRNAs are targets of altered microRNAs. Using pathway analysis, we evaluated the relevance of such microRNA deregulations to genotoxicity. This revealed eight microRNAs that appear to participate in specific BaP-responsive pathways relevant to genotoxicity, such as apoptotic signaling, cell cycle arrest, DNA damage response, and DNA damage repair. Our results particularly highlight the potential of microRNA-29b, microRNA-26a-1*, and microRNA-122* as novel players in the BaP response. Therefore, this study demonstrates the added value of an integrated microRNA-mRNA approach for identifying molecular mechanisms induced by BaP in an in vitro human model. PMID- 22316171 TI - Dutasteride for the treatment of prostate-related conditions. AB - INTRODUCTION: A variety of pharmaceuticals have been developed directed at mitigating the symptoms associated with benign prostatic hypertrophy (BPH) and have also been evaluated for their potential role in prevention and treatment of prostate cancer. One such agent is dutasteride , a non-selective inhibitor of 5alpha-reductase, an enzyme responsible for conversion of testosterone to a more potent androgen dihydrotestosterone (DHT). AREAS COVERED: This review will cover the safety profile of dutasteride when it is used in the treatment of prostate related conditions, specifically looking at the pivotal clinical trials on this drug. EXPERT OPINION: Dutasteride has proved to be a safe and efficacious treatment for symptoms related to BPH. The primary safety concern relates to the increased incidence of high-grade prostate cancer seen in men treated with dutasteride in the setting of prostate cancer prevention. Dutasteride has a role as an adjunct in the treatment of prostate cancer; however, this is an area still under active investigation. It is not recommended for use in prostate cancer prevention given the increased risk of high-grade cancers. PMID- 22316172 TI - Prolonged urinary detection times of EtG and EtS in patients with decreased renal function. AB - BACKGROUND: The aims of this study were to investigate detection times for ethyl glucuronide (EtG) and ethyl sulphate (EtS) in urine samples of patients with decreased kidney function and to compare these with those previously reported for healthy volunteers. METHODS: Fourteen patients were included, each delivering 10 urine samples after a nonsupervised intake of 0.1 to 1.4 g ethanol/kg body weight. The urinary detection times of EtG and EtS in these patients were adjusted for doses and compared to previously published healthy volunteers. RESULTS: Detection times were significantly longer in patients with decreased renal function compared with healthy volunteers (p < 0.01 for both EtG and EtS). CONCLUSIONS: Even after very minor alcohol intakes, these patients could fail alcohol tests based on the detection of conjugated ethanol metabolites for several days and wrongly be suspected of higher or more recent alcohol intakes than actually have found place. PMID- 22316173 TI - Ethanolic extract of Rubia peregrina L. (Rubiaceae) inhibits haloperidol-induced catalepsy and reserpine-induced orofacial dyskinesia. AB - In the traditional Sardinian system of medicine, Rubia peregrina L. (Rubiaceae) is reported as an aphrodisiac herb. Since the aphrodisiacs may also have antioxidant and dopaminergic activities, the aim of this study was to study the effect of ethanolic extract of aerial parts of R. peregrina for the scavenging of free DPPH radicals and the inhibition of haloperidol-induced catalepsy in mice and reserpine-induced orofacial dyskinesia in rats. The extract exhibited significant antioxidant activity in a free radical DPPH assay with IC(50) = 55.6 ug mL(-1), which was very close to IC(50) of ascorbic acid. The extract of R. peregrina (100 and 200 mg kg(-1) intraperitoneally, i.p.) significantly inhibited haloperidol (1 mg kg(-1) i.p.) - induced catalepsy in mice (p < 0.01). In rats, the extract (200 mg kg(-1) i.p.) significantly (p < 0.01) inhibited the orofacial dyskinesia induced by intraperitoneal administration of reserpine (1 mg kg(-1) on days 1, 3 and 5). This study demonstrates that R. peregrina has antioxidant activity and improves the dopaminergic function. Results therefore justify the development of further experiments to investigate the psychopharmacological profile of R. peregrina. PMID- 22316174 TI - Safety evaluation of 32P-chromic phosphate-poly L lactic acid particles interstitially implanted into livers of Beagle dogs. AB - AIMS: The aim of this study was to investigate the safety and toxicity of biodegradable (32)P-chromic phosphate-poly L lactic acid ((32)P-CP-PLLA) particles interstitially implanted into Beagle dog livers. METHODS: Eighteen healthy Beagle dogs were randomly divided into 6 groups (n=3), and were treated with drugs of different formulations or doses, as well as controls. At different time points after surgery, the experimental dogs were weighed. Detection of indicators of blood chemistry and liver fibrosis, SPECT bremsstrahlung imaging, computed tomography, histological examination, continuous blood measurement, and counting of urine and fecal radioactivity were performed for these dogs. RESULTS: SPECT imaging showed that after implantation of radioactive particles into livers, radioactivity continuously accumulated in the implanted sites, while no radioactivity imaging was found in the nonimplantation sites. The mean absorbance doses in the implantation sites were 89.8-178.7 Gy. Local spherical lesions were observed in tissues. The average effective half-life time of (32)P-CP-PLLA was 11.8 days. Within 4 weeks after surgery, slight or moderate swelling and degradation of liver cells were detected, while in 8 weeks after surgery, they are normal. For the blood chemistry, liver fibrosis, and other indicators, no significant differences were found between the control groups and particle implantation groups (F=1.378, p=0.232). CONCLUSIONS: (32)P-CP-PLLA particles have advantages including good targeting, immobile, being degradable in vivo, easy to be protected, and so on. It is suitable for treating solid tumors with blood supply. (32)P-CP-PLLA particles are a kind of safe, novel, radioactive implantation drug. PMID- 22316175 TI - Protein-protein interactions and substrate channeling in orthologous and chimeric aldolase-dehydrogenase complexes. AB - Bacterial aldolase-dehydrogenase complexes catalyze the last steps in the meta cleavage pathway of aromatic hydrocarbon degradation. The aldolase (TTHB246) and dehydrogenase (TTHB247) from Thermus thermophilus were separately expressed and purified from recombinant Escherichia coli. The aldolase forms a dimer, while the dehydrogenase is a monomer; these enzymes can form a stable tetrameric complex in vitro, consisting of two aldolase and two dehydrogenase subunits. Upon complex formation, the K(m) value of 4-hydroxy-2-oxopentanoate, the substrate of TTHB246, is decreased 4-fold while the K(m) of acetaldehyde, the substrate of TTHB247, is increased 3-fold. The k(cat) values of each enzyme were reduced by ~2-fold when they were in a complex. The half-life of TTHB247 at 50 degrees C increased by ~4 fold when it was in a complex with TTHB246. The acetaldehyde product from TTHB246 could be efficiently channelled directly to TTHB247, but the channeling efficiency for the larger propionaldehyde was ~40% lower. A single A324G substitution in TTHB246 increased the channeling efficiency of propionaldehyde to a value comparable to that of acetaldehyde. Stable and catalytically competent chimeric complexes could be formed between the T. thermophilus enzymes and the orthologous aldolase (BphI) and dehydrogenase (BphJ) from the biphenyl degradation pathway of Burkholderia xenovorans LB400. However, channeling efficiencies for acetaldehyde in these chimeric complexes were ~10%. Structural and sequence analysis suggests that interacting residues in the interface of the aldolase-dehydrogenase complex are highly conserved among homologues, but coevolution of partner enzymes is required to fine-tune this interaction to allow for efficient substrate channeling. PMID- 22316176 TI - Impact of dental visiting trajectory patterns on clinical oral health and oral health-related quality of life. AB - BACKGROUND: Previous studies have shown variation in long-term dental visiting but little is known about the oral health outcomes of such variation. OBJECTIVE: The objective of this study is to determine the association of different dental visiting trajectories with dental clinical and oral health-related quality of life (OHRQoL) indicators. METHODS: This study utilized data from the Dunedin Multidisciplinary Health and Development Study, a continuing longitudinal study of 1,037 babies born in Dunedin (New Zealand) between April 1, 1972 and March 31, 1973. Data presented here were collected at ages 15, 18, 26, and 32 years. Three categories of dental attendance were identified in earlier research, namely: regulars (n = 285, 30.9 percent of the cohort), decliners (441, 55.9 percent), and opportunistic users (107, 13.1 percent). RESULTS: There was a statistically significant association between opportunistic dental visiting behavior and decayed missing and filled surfaces score (Beta = 3.9) as well as missing teeth because of caries (Beta = 0.7). Nonregular dental visiting trajectories were associated with higher Oral Health Impact Profile (OHIP-14) scores (Beta = 2.1) and lower self-rated oral health scores (prevalence ratio = 0.8). CONCLUSION: Long-term, postchildhood dental attendance patterns are associated with oral health in adulthood, whether defined by clinical dental indicators or OHRQoL. Improving dental visiting behavior among low socioeconomic status groups would have the greatest effect on improving oral health and reducing oral health impacts. PMID- 22316177 TI - Highly regio- and stereoselective ruthenium(II)-catalyzed direct ortho alkenylation of aromatic and heteroaromatic aldehydes with activated alkenes under open atmosphere. AB - Various aromatic and heteroaromatic aldehydes reacted with activated alkenes in the presence of a catalytic amount of [{RuCl(2)(p-cymene)}(2)], AgSbF(6), and Cu(OAc)(2).H(2)O to give substituted alkene derivatives in a highly regio- and stereoselective manner. The corresponding alkene derivatives were further converted into unusual four-membered cyclic ketones or a polycyclic isochromanone derivative via a photochemical rearrangement. Notably, the catalytic reaction was conducted under an open atmosphere. PMID- 22316178 TI - Synthesis and structure resolution of RbLaF4. AB - The synthesis and structure resolution of RbLaF(4) are described. RbLaF(4) is synthesized by solid-state reaction between RbF and LaF(3) at 425 degrees C under a nonoxidizing atmosphere. Its crystal structure has been resolved by combining neutron and synchrotron powder diffraction data refinements (Pnma,a = 6.46281(2) A, b = 3.86498(1) A, c = 16.17629(4) A, Z = 4). One-dimensional (87)Rb, (139)La, and (19)F MAS NMR spectra have been recorded and are in agreement with the proposed structural model. Assignment of the (19)F resonances is performed on the basis of both (19)F-(139)La J-coupling multiplet patterns observed in a heteronuclear DQ-filtered J-resolved spectrum and (19)F-(87)Rb HMQC MAS experiments. DFT calculations of both the (19)F isotropic chemical shieldings and the (87)Rb, (139)La electric field gradient tensors using the GIPAW and PAW methods implemented in the CASTEP code are in good agreement with the experimental values and support the proposed structural model. Finally, the conductivity of RbLaF(4) and luminescence properties of Eu-doped LaRbF(4) are investigated. PMID- 22316179 TI - Daily vacuuming of mattresses significantly reduces house dust mite allergens, bacterial endotoxin, and fungal beta-glucan. AB - BACKGROUND AND AIMS: Atopic patients are advised to cover their mattresses with occlusive coverings; however, these are not cheap. We investigated whether daily vacuum cleaning of mattresses significantly reduces content of house dust mite allergens, bacterial endotoxin, and fungal beta-glucan. METHODS: Twenty volunteers vacuumed their mattress daily for 8 weeks. Dust samples collected at two weekly intervals were analyzed for house dust mite allergens (Der p 1 and Der f 1) by double monoclonal antibody ELISA and for endotoxin and beta-glucan by the Limulus amoebocyte lysate kinetic assay. Results are presented as geometric means with 95% confidence interval (CI). RESULTS: Total house dust mite allergens (Der p 1 + Der f 1) significantly reduced from a geometric mean (95% CI) of 4.07 MUg (2.44-6.79) at the start to 0.42 MUg (0.21-0.81) at week 8. Total endotoxin and beta-glucan were also significantly reduced from 13.6 EU (8.6-21.4) to 3.4 EU (2.3-5.0) and from 94.4 MUg (57.1-156.2) to 19.7 MUg (10.2-37.9), respectively (p for trend >.0001). Percentage reductions in total house dust mite allergens, endotoxin, and beta-glucan after 8 weeks of daily vacuum cleaning were 85.1% (80.1-90.1), 71.0% (70.4-81.0), and 75.7% (70.4-81.0), respectively. This was mainly due to a 77.7% (70.8-84.7) reduction in total dust. CONCLUSION: Daily vacuum cleaning of mattresses over time significantly reduces house dust mite allergens, endotoxin, and beta-glucan. This gives atopic patients a practical and cheaper alternative to reduce their exposure to indoor house dust mite allergens and microbial bio-contaminants. PMID- 22316180 TI - Development of a cDNA microarray for the measurement of gene expression in the sheep scab mite Psoroptes ovis. AB - BACKGROUND: Sheep scab is caused by the ectoparasitic mite Psoroptes ovis which initiates a profound cutaneous inflammatory response, leading to the development of the skin lesions which are characteristic of the disease. Existing control strategies rely upon injectable endectocides and acaricidal dips but concerns over residues, eco-toxicity and the development of acaricide resistance limit the sustainability of this approach. In order to identify alternative means of disease control, a deeper understanding of both the parasite and its interaction with the host are required. METHODS: Herein we describe the development and utilisation of an annotated P. ovis cDNA microarray containing 3,456 elements for the measurement of gene expression in this economically important ectoparasite. The array consists of 981 P. ovis EST sequences printed in triplicate along with 513 control elements. Array performance was validated through the analysis of gene expression differences between fed and starved P. ovis mites. RESULTS: Sequences represented on the array include homologues of major house dust mite allergens and tick salivary proteins, along with factors potentially involved in mite reproduction and xenobiotic metabolism. In order to validate the performance of this unique resource under biological conditions we used the array to analyse gene expression differences between fed and starved P. ovis mites. These analyses identified a number of house dust mite allergen homologues up-regulated in fed mites and P. ovis transcripts involved in stress responses, autophagy and chemosensory perception up-regulated in starved mites. CONCLUSION: The P. ovis cDNA microarray described here has been shown to be both robust and reproducible and will enable future studies to analyse gene expression in this important ectoparasite. PMID- 22316181 TI - Quality and safety of medication use in primary care: consensus validation of a new set of explicit medication assessment criteria and prioritisation of topics for improvement. AB - BACKGROUND: Addressing the problem of preventable drug related morbidity (PDRM) in primary care is a challenge for health care systems internationally. The increasing implementation of clinical information systems in the UK and internationally provide new opportunities to systematically identify patients at risk of PDRM for targeted medication review. The objectives of this study were (1) to develop a set of explicit medication assessment criteria to identify patients with sub-optimally effective or high-risk medication use from electronic medical records and (2) to identify medication use topics that are perceived by UK primary care clinicians to be priorities for quality and safety improvement initiatives. METHODS: For objective (1), a 2-round consensus process based on the RAND/UCLA Appropriateness Method (RAM) was conducted, in which candidate criteria were identified from the literature and scored by a panel of 10 experts for 'appropriateness' and 'necessity'. A set of final criteria was generated from candidates accepted at each level. For objective (2), thematically related final criteria were clustered into 'topics', from which a panel of 26 UK primary care clinicians identified priorities for quality improvement in a 2-round Delphi exercise. RESULTS: (1) The RAM process yielded a final set of 176 medication assessment criteria organised under the domains 'quality' and 'safety', each classified as targeting 'appropriate/necessary to do' (quality) or 'inappropriate/necessary to avoid' (safety) medication use. Fifty-two final 'quality' assessment criteria target patients with unmet indications, sub-optimal selection or intensity of beneficial drug treatments. A total of 124 'safety' assessment criteria target patients with unmet needs for risk-mitigating agents, high-risk drug selection, excessive dose or duration, inconsistent monitoring or dosing instructions. (2) The UK Delphi panel identified 11 (23%) of 47 scored topics as 'high priority' for quality improvement initiatives in primary care. CONCLUSIONS: The developed criteria set complements existing medication assessment instruments in that it is not limited to the elderly, can be implemented in electronic data sets and focuses on drug groups and conditions implicated in common and/or severe PDRM in primary care. Identified priorities for quality and safety improvement can guide the selection of targets for initiatives to address the PDRM problem in primary care. PMID- 22316182 TI - The cholinergic system and inflammation: common pathways in delirium pathophysiology. AB - OBJECTIVES: To investigate whether delirium is associated with an unbalanced inflammatory response or a dysfunctional interaction between the cholinergic and immune systems. DESIGN: Cohort observational study. SETTING: General hospital orthopedic ward. PARTICIPANTS: One hundred one individuals aged 60 and older with no previous cognitive impairment undergoing elective arthroplasty. MEASUREMENTS: Incidence of postoperative delirium, plasma cholinesterase activity (acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)) and inflammatory mediators (C-reactive protein (CRP), interleukin (IL)-1 beta, tumor necrosis factor alpha, IL-6, IL-8, IL-10) before and after surgery. RESULTS: Thirty-seven participants developed postoperative delirium and had greater production of CRP and proinflammatory to anti-inflammatory ratio after surgery. In participants with delirium, but not in controls, preoperative levels of plasma cholinesterase activity correlated with DeltaCRP (AChE: rho = 0.428, P = .008 and BuChE: rho = 0.423, P = .009), DeltaIL-6 (AChE: rho = 0.339, P = .04), and DeltaP/A ratio (AChE: rho = 0.346, P = .04). CONCLUSION: Delirium was associated not only with an unbalanced inflammatory response, but also with a dysfunctional interaction between the cholinergic and immune systems. Comprehensive understanding of the relationship between the cholinergic and immune systems is crucial to developing new insights into delirium pathophysiology and novel therapeutic interventions. PMID- 22316183 TI - Silver-catalyzed decarboxylative chlorination of aliphatic carboxylic acids. AB - Decarboxylative halogenation of carboxylic acids, the Hunsdiecker reaction, is one of the fundamental functional group transformations in organic chemistry. As the initial method requires the preparations of strictly anhydrous silver carboxylates, several modifications have been developed to simplify the procedures. However, these methods suffer from the use of highly toxic reagents, harsh reaction conditions, or limited scope of application. In addition, none is catalytic for aliphatic carboxylic acids. In this Article, we report the first catalytic Hunsdiecker reaction of aliphatic carboxylic acids. Thus, with the catalysis of Ag(Phen)(2)OTf, the reactions of carboxylic acids with t-butyl hypochlorite afforded the corresponding chlorodecarboxylation products in high yields under mild conditions. This method is not only efficient and general, but also chemoselective. Moreover, it exhibits remarkable functional group compatibility, making it of more practical value in organic synthesis. The mechanism of single electron transfer followed by chlorine atom transfer is proposed for the catalytic chlorodecarboxylation. PMID- 22316184 TI - Recommended number of strides for automatic assessment of gait symmetry and regularity in above-knee amputees by means of accelerometry and autocorrelation analysis. AB - BACKGROUND: Symmetry and regularity of gait are essential outcomes of gait retraining programs, especially in lower-limb amputees. This study aims presenting an algorithm to automatically compute symmetry and regularity indices, and assessing the minimum number of strides for appropriate evaluation of gait symmetry and regularity through autocorrelation of acceleration signals. METHODS: Ten transfemoral amputees (AMP) and ten control subjects (CTRL) were studied. Subjects wore an accelerometer and were asked to walk for 70 m at their natural speed (twice). Reference values of step and stride regularity indices (Ad1 and Ad2) were obtained by autocorrelation analysis of the vertical and antero posterior acceleration signals, excluding initial and final strides. The Ad1 and Ad2 coefficients were then computed at different stages by analyzing increasing portions of the signals (considering both the signals cleaned by initial and final strides, and the whole signals). At each stage, the difference between Ad1 and Ad2 values and the corresponding reference values were compared with the minimum detectable difference, MDD, of the index. If that difference was less than MDD, it was assumed that the portion of signal used in the analysis was of sufficient length to allow reliable estimation of the autocorrelation coefficient. RESULTS: All Ad1 and Ad2 indices were lower in AMP than in CTRL (P < 0.0001). Excluding initial and final strides from the analysis, the minimum number of strides needed for reliable computation of step symmetry and stride regularity was about 2.2 and 3.5, respectively. Analyzing the whole signals, the minimum number of strides increased to about 15 and 20, respectively. CONCLUSIONS: Without the need to identify and eliminate the phases of gait initiation and termination, twenty strides can provide a reasonable amount of information to reliably estimate gait regularity in transfemoral amputees. PMID- 22316185 TI - Building upon validated facial scales. PMID- 22316186 TI - Validated composite assessment scales for the global face. AB - BACKGROUND: Twenty grading scales have been developed to assess age-related facial changes. Until now, the validity with regard to the patient's actual age and the clinical importance of combined measurement tools to describe facial aging was unclear. OBJECTIVE: To investigate the reliability and validity of a total face score and three global face assessment scales for estimated age, estimated aesthetic treatment effort, and signs of aging in the facial units. MATERIALS AND METHODS: Descriptive, reliability, correlation, and principal component analyses based on the assessment of 50 subjects by 12 raters using the 20 grading scales and the global face assessment scales. RESULTS: Inter- and intrarater reliability was high for the total face score and for the scales on estimated age and aesthetic treatment effort. Actual age was highly correlated with these three measures. Facial aging was indicated particularly by scales of the lower face. CONCLUSION: The aesthetic grading scales and global scales on estimated age and aesthetic treatment effort are reliable and valid instruments. The results suggest that a more-comprehensive evaluation of the human face and its age-related changes can help to identify important areas of facial aging and to define optimal aesthetic treatment strategies. PMID- 22316187 TI - Validated assessment scales for the upper face. AB - BACKGROUND: Age-related upper face changes such as wrinkles, lines, volume loss, and anatomic alterations may affect quality of life and psychological well-being. The development of globally accepted tools to assess these changes objectively is an essential contribution to aesthetic research and routine clinical medicine. OBJECTIVE: To establish the reliability of several upper face scales for clinical research and practice: forehead lines, glabellar lines, crow's feet (at rest and dynamic expression), sex-specific brow positioning, and summary scores of forehead and crow's feet areas and of the entire upper face unit. METHODS AND MATERIALS: Four 5-point photonumerical rating scales were developed to assess glabellar lines and sex-specific brow positioning. Twelve experts rated identical upper face photographs of 50 subjects in two separate rating cycles using all eight scales. Responses of raters were analyzed to assess intra- and interrater reliability. RESULTS: Interrater reliability was substantial for all upper face scales, aesthetic areas, and the upper face score except for the brow positioning scales. Intrarater reliability was high for all scales and resulting scores. CONCLUSION: Except for brow positioning, the upper face rating scales are reliable tools for valid and reproducible assessment of the aging process. PMID- 22316188 TI - Validated assessment scales for the mid face. AB - BACKGROUND: The improvement of aesthetic treatment options for age-related mid face changes, such as volume loss, and the increase in patient expectations necessitates the development of more-complex and globally accepted assessment tools. OBJECTIVE: To develop three grading scales for objective assessment of the infraorbital hollow and upper and lower cheek fullness and to establish the reliability of these scales for clinical research and practice. METHODS AND MATERIALS: Three 5-point rating scales were developed to assess infraorbital hollow and upper and lower cheek fullness objectively. Twelve experts rated identical mid face photographs of 50 subjects in two separate rating cycles using the mid face scales. Test responses of raters were analyzed to assess intra- and interrater reliability. RESULTS: Interrater reliability was substantial for the infraorbital hollow, upper cheek fullness, and lower cheek fullness scales. Intrarater reliability was high for all three scales. Both of the cheek fullness scales yielded higher reliabilities when three rather than two views were used to assess the volume changes of the cheek. CONCLUSION: The mid face scales are reliable tools for valid and reproducible assessment of age-related mid face changes. PMID- 22316189 TI - Validated assessment scales for the lower face. AB - BACKGROUND: Aging in the lower face leads to lines, wrinkles, depression of the corners of the mouth, and changes in lip volume and lip shape, with increased sagging of the skin of the jawline. Refined, easy-to-use, validated, objective standards assessing the severity of these changes are required in clinical research and practice. OBJECTIVE: To establish the reliability of eight lower face scales assessing nasolabial folds, marionette lines, upper and lower lip fullness, lip wrinkles (at rest and dynamic), the oral commissure and jawline, aesthetic areas, and the lower face unit. METHODS AND MATERIALS: Four 5-point rating scales were developed to objectively assess upper and lower lip wrinkles, oral commissures, and the jawline. Twelve experts rated identical lower face photographs of 50 subjects in two separate rating cycles using eight 5-point scales. Inter- and intrarater reliability of responses was assessed. RESULTS: Interrater reliability was substantial or almost perfect for all lower face scales, aesthetic areas, and the lower face unit. Intrarater reliability was high for all scales, areas and the lower face unit. CONCLUSION: Our rating scales are reliable tools for valid and reproducible assessment of the aging process in lower face areas. PMID- 22316191 TI - Unusual isomeric corniculatolides from mangrove, Aegiceras corniculatum. AB - Four new isomeric macrolides of combretastatin D-2 congeners named isocorniculatolide A (1), 11-O-methylisocorniculatolide A (2), 11-O methylcorniculatolide A (3), and 12-hydroxy-11-O-methylcorniculatolide A (4), and the known corniculatolide A (5), arjunolic acid, and maslinic acid were isolated from the CHCl(3) extract of the bark of Aegiceras corniculatum. The structures of the new compounds (1-4) were elucidated by a combination of spectroscopic analysis (1-5), chemical modifications, and single-crystal X-ray analysis (1). PMID- 22316190 TI - Validated assessment scale for neck volume. AB - BACKGROUND: Sagging of the neck aesthetic area is an important indicator of age. The development of complex and globally accepted tools for proper assessment of the change in neck volume is an essential contribution to aesthetic research and the routine clinical setting. OBJECTIVE: To develop a grading scale for the objective assessment of the neck volume and to establish the reliability of this scale for clinical research and practice. MATERIALS AND METHODS: A 5-point rating scale was developed to assess neck volume objectively. Twelve experts rated frontal and lateral neck photographs of 50 subjects in two separate rating cycles using the neck volume scale. Responses of raters were analyzed to assess inter- and intrarater reliability. RESULTS: Interrater reliability for the neck volume scale was almost perfect, with intraclass correlation coefficients for the first and second rating cycles of 0.85 and 0.84, respectively. Intrarater reliability for the neck volume scale was high (0.90) and Pearson correlation coefficients ranged between 0.88 and 0.95 and were statistically significant. CONCLUSION: The neck volume scale demonstrates optimal reliability for clinical research and practice. PMID- 22316192 TI - Peer review under the microscope: an editor's view. PMID- 22316193 TI - A focus on snake venoms and antivenins. PMID- 22316194 TI - Overview and controversies in the medical management of pit viper envenomation in the dog. AB - OBJECTIVE: To provide a review and update on the medical management of pit viper envenomation in dogs. ETIOLOGY: Pit viper snake (Crotalidae) envenomation in dogs is a common emergency in the United States. At least 50 enzymes contribute to snake venom potency that causes soft tissue damage, vasculotoxicity, coagulopathy, cytotoxicity, and necrosis. DIAGNOSIS: Snakebite envenomation may be identified by fang puncture wounds but primarily as a focal site with a rapid onset of severe swelling, hemorrhage, pain, and potentially necrosis. Crotalid venom causes hematologic abnormalities, local tissue damage, hypotension, and occasionally neurological impairment. The most marked hematologic abnormalities include thrombocytopenia, hemolytic anemia, and various forms of coagulopathy, including defibrination without disseminated intravascular coagulation (in North America), summarized as a venom-induced coagulopathy. THERAPY: The mainstay of treatment includes intravenous crystalloid fluid therapy, antivenom, and analgesic medications. Currently available antivenom products include a mixed polyvalent Antivenin (Crotalidae) Polyvalent (ACP(a)), and Crotalinae polyvalent immune Fab (Crofab(b)). There are products from Mexico and Costa Rica that have limited availability, a similar imported Fab product (Antivipmyn(c)), and a polyspecific antivenom (Polyvet-ICP(d)), respectively. Glucocorticoids, nonsteroidal antiinflammatory drugs (NSAIDs) and antihistamines are not included in the majority of recommended treatment protocols by world authorities; however, there are some reports that describe their use. Antimicrobial therapy and blood products are used only when clinically indicated. There is a vaccine available, but at present, it is of unknown efficacy because of a lack of documented scientific information. PROGNOSIS: Mortality from North American crotalid envenomation is generally rare and is influenced by several variables, including the amount of venom injected, the size and species of snake, the size of the victim, the location of the bite, time elapsed until treatment, and the therapy initiated. Mortality rates range from 1% to 30%. PMID- 22316195 TI - A review of current indications, adverse effects, and administration recommendations for intravenous immunoglobulin. AB - OBJECTIVE: To review and summarize the body of literature regarding human intravenous immunoglobulin (hIVIG) therapy in veterinary medicine. Mechanism of action, usage in human medicine, adverse effects of therapy, implications for veterinary use, and administration recommendations are discussed. DATA SOURCES: Current human and veterinary peer-reviewed medical literature including original research articles and scientific reviews. HUMAN DATA SYNTHESIS: There are currently 6 labeled uses for hIVIG in human medicine, but preparations are used off-label to successfully treat multiple immune-mediated conditions. To maximize the potential of hIVIG use in animals and identify areas deficient in research, a review of the current literature is warranted. VETERINARY DATA SYNTHESIS: Investigation of hIVIG therapy in veterinary patients has been limited to the subjects of immune-mediated hemolytic anemia (IMHA), immune-mediated thrombocytopenia (ITP), Evan's syndrome, cutaneous disease, myasthenia gravis (MG), and sudden acquired retinal degeneration (SARDS). Proponents of veterinary hIVIG use believe administration may reduce transfusion requirements and decrease hospitalization time. CONCLUSION: Immunoglobulin (Ig) has not been shown to decrease transfusion requirements in IMHA patients, but shows great promise for treatment of ITP and dermatological diseases. Although serial transfusion of hIVIG is employed in human medicine, repeated transfusion is not recommended in animals due to risk of severe allergic reaction. Other potential adverse effects of transfusion include delayed hypersensitivity reactions, thromboembolism, renal failure, hypotension, and aseptic meningitis. PMID- 22316196 TI - A review of stress-related mucosal disease. AB - OBJECTIVE: To review and summarize the human and veterinary literature regarding stress-related mucosal disease (SRMD) pathogenesis, patient risk factors, and therapeutic options for prophylaxis and treatment. ETIOLOGY: SRMD is a common sequela of critical illness in human patients. Development of SRMD results from splanchnic hypoperfusion, reperfusion injury, and exposure of the gastric mucosa to acid, pepsin, and bile acids following breakdown of the gastric mucosal defense system. Human patients with the highest risk of stress ulceration include those with respiratory failure necessitating mechanical ventilation greater than 48 h or coagulopathy. Currently, little is known about the incidence and pathophysiology of SRMD in critically ill veterinary patients. DIAGNOSIS: A presumptive diagnosis can be made in high-risk patient populations following detection of occult or gross blood in nasogastric tube aspirates, hematemesis, or melena. Definitive diagnosis is achieved via esophagogastroduodenoscopy. Lesions are localized to the acid-producing portions of the stomach, the fundus, and body. THERAPY: Therapy is aimed at optimization of tissue perfusion and oxygenation. Pharmacologic interventions are instituted to increase intraluminal pH and augment natural gastric defenses. Histamine(2)-receptor antagonists, proton pump inhibitors, and sucralfate are the mainstays of therapy. In people, clinically significant bleeding may necessitate additional interventions (eg, packed red blood cell transfusions, endoscopic, or surgical hemostasis). PROGNOSIS: Mortality is increased in people with clinically significant bleeding compared to those patients who do not bleed. Institution of prophylaxis is recommended in high-risk patients. However, no consensus exists regarding initiation of prophylaxis, preference of frontline drug class, or indication for discontinuation of therapy. The prognosis of veterinary patients with SRMD remains unknown at this time. PMID- 22316197 TI - Ventilator waveform interpretation in mechanically ventilated small animals. AB - OBJECTIVE: To review the topic of ventilator waveforms analysis with emphasis on interpretation of ventilator waveforms and their use in the management and monitoring of mechanically ventilated small animal patients. DATA SOURCES: Human clinical studies, scientific reviews, and textbooks, as well as veterinary textbooks and clinical examples of ventilator waveforms in mechanically ventilated dogs. SUMMARY: Ventilator waveforms are graphic representations of data collected from the ventilator and reflect patient-ventilator interactions. The 4 parameters pressure, volume, flow, and time are most descriptive of mechanical ventilation. Typically, 3 different graphs, also referred to as scalars, consisting of pressure versus time, volume versus time, and flow versus time, with time always plotted on the x-axis, are used. Changes in the ventilator settings as well as in the characteristics of the lungs such as airway resistance (R(aw)) and respiratory system compliance (C(rs)) can be recognized from specific variations in the waveforms. Flow-volume and pressure-volume loops provide additional information about changes in lung function. Patient-ventilator dyssynchrony is a common problem during mechanical ventilation and can lead to patient discomfort and an increased work of breathing. Ventilator waveforms are helpful to identify dyssynchrony, which can be divided into trigger, flow, cycle, and expiratory dyssynchrony. Ventilator waveforms allow the clinician to assess changes in respiratory mechanics, and can be useful in monitoring the progression of disease pathology and response to therapy. Adjustments in ventilator settings based on proper analysis and interpretation of these waveforms can help the clinician to optimize ventilation therapy. CONCLUSIONS: Ventilator waveforms are graphic representations of patient-ventilator interactions. Proper interpretation of ventilator waveforms affords the critical care clinician a better understanding of the patient's respiratory function, response to therapy, and causes for patient-ventilator dyssynchrony. Ventilator waveform interpretation is an important tool in the assessment and management of mechanically ventilated small animal patients. PMID- 22316198 TI - The use of deep oral swabs as a surrogate for transoral tracheal wash to obtain bacterial cultures in dogs with pneumonia. AB - OBJECTIVE: To determine agreement in bacterial culture and susceptibility (BC&S) between deep oral swab (DOS) and routine transoral tracheal wash (TOTW) in dogs with pneumonia. DESIGN: Prospective study, performed between 2008 and 2010 with no follow-up period. SETTING: University teaching hospital. ANIMALS: Five puppies and 5 adult dogs with community or hospital-acquired pneumonia. MEASUREMENTS AND MAIN RESULTS: A DOS was collected from each patient; dogs were then briefly anesthetized with propofol(a) for a routine TOTW. Routine microbiology techniques were used for culture. Positive culture results were obtained from all 20 swabs. Results of BC&S were compared between the 2 sites. In all puppies, there was no agreement between DOS and TOTW. In adult dogs, 2 patients with hospital-acquired infection (HAI) had complete agreement between the BC&S results from DOS and TOTW. Two adult dogs had some similarity in BC&S results, and the final dog had no relationship between cultures. CONCLUSIONS: DOS is not an appropriate alternative to TOTW to obtain samples for BC&S in puppies with pneumonia. In adult dogs, traditional TOTW remains the gold standard, but DOS may be considered in dogs with suspected HAI. Further work is needed to confirm this preliminary finding. PMID- 22316199 TI - Ionized hypocalcemia as a prognostic indicator in dogs following trauma. AB - OBJECTIVE: To determine the incidence of ionized hypocalcemia (iHCa) in dogs with blunt and penetrating traumatic injuries upon presentation to a hospital, and to determine the association of iHCa with mortality, duration of hospitalization, and requirement for intensive care therapies. DESIGN: Retrospective study (January 2007-December 2008). SETTING: University veterinary teaching hospital. ANIMALS: Eighty-eight dogs admitted to the ICU within 24 hours of a traumatic event and with assessment of a venous blood gas sample, including ionized calcium, at hospital admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Most dogs (72%) sustained injuries as a result of a motor vehicle accident. iHCa (<1.25 mmol/L [<2.50 mEq/L]) was present in 14 of 88 dogs (16%). Dogs with abdominal trauma were significantly more likely to have iHCa (P = 0.020) than dogs with other injuries. Dogs with iHCa spent significantly longer time in the hospital (P = 0.036) and ICU (P = 0.005), and were more likely to require oxygen supplementation (P = 0.048), synthetic colloids (P = 0.020), vasopressors (P = 0.0043), and blood transfusions (P < 0.0001). Six of 14 dogs (43%) with iHCa demonstrated clinical signs consistent with hypocalcemia during the course of hospitalization, and calcium gluconate was administered intravenously to one dog. Overall mortality was 16% (14/88) and dogs with iHCa were significantly less likely to survive (P < 0.001). CONCLUSIONS: The incidence of iHCa upon hospital admission in this group of dogs with blunt and penetrating trauma is similar to the incidence of iHCa in critically ill dogs. Findings further suggest that dogs with iHCa are more severely injured and subsequently require increased intensive care therapies and have a lower likelihood of survival compared to dogs with normocalcemia. Ionized calcium concentration may therefore be a useful prognostic indicator in dogs with blunt and penetrating traumatic injuries. PMID- 22316200 TI - Outcome and medical management in dogs with lower motor neuron disease undergoing mechanical ventilation: 14 cases (2003-2009). AB - OBJECTIVE: To describe the application of intermittent positive pressure ventilation (IIPV) in dogs with lower motor neuron disease (LMND). DESIGN: Multi institutional, retrospective study (2003-2009). SETTING: Intensive care units at multiple university teaching hospitals. ANIMALS: Fourteen dogs with LMND that underwent IIPV. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The ventilatory logs of 4 teaching hospitals were searched for dogs undergoing IIPV in association with a diagnosis of acute LMND. The medical records were evaluated for signalment, specific LMND, ventilatory management and duration, complications associated with ventilation, duration of hospitalization, and outcome. Descriptive statistics were used as indicated. Fifteen records were evaluated, 1 dog was excluded since it experienced cardiopulmonary arrest (CPA) before commencement of IIPV. The median age was 7.0 years (range 10 mo to 12 y). There were 5 Labrador retrievers, 4 mixed breeds, and 5 other breeds were each represented once. Five dogs were diagnosed with myasthenia gravis, 4 dogs with polyradiculoneuritis, and 5 dogs had an undetermined LMND. Clinical signs of weakness before ventilation were present for a median of 36 hours (range 6 h to 14 d). Dogs were ventilated for a median of 109 hours (range 5-261 h). Nine dogs had temporary tracheostomies performed, and 8 dogs received nutritional support. Five dogs developed ventilator associated pneumonia. Six dogs were successfully weaned from the ventilator with a median ventilatory time of 49 hours (range 25 192 h). Three dogs survived to discharge. No single LMND was associated with a better outcome. CONCLUSIONS: High euthanasia rates and iatrogenic complications limit the ability to accurately prognosticate for affected dogs in this retrospective study, but in dogs with LMND that is severe enough to require IIPV, support may be required days to weeks. PMID- 22316201 TI - Magnesium sulfate as an adjunct therapy in the management of severe generalized tetanus in a dog. AB - OBJECTIVE: To describe the use of magnesium sulfate in a case of generalized tetanus in a dog. CASE SUMMARY: A 1.5-year-old golden retriever was presented for a digital wound on the right thoracic limb and clinical signs associated with generalized tetanus. Initial case management consisted of wound debridement, treatment with metronidazole, tetanus immunoglobulin, methocarbamol, airway management via tracheostomy, and nursing care. Sedation to control severe muscle spasms became insufficient despite increasing doses of benzodiazepine, methocarbamol, and barbiturate continuous rate infusions. A magnesium sulfate continuous rate infusion was instituted on day 7 and muscle rigidity improved within 16 hours allowing discontinuation of sedative infusions over the subsequent 2 days. Clinical improvement continued and the dog was discharged on day 14. NEW OR UNIQUE INFORMATION PROVIDED: This case demonstrates the use of supraphysiologic magnesium in the treatment of severe generalized tetanus with a positive outcome. No clinical signs associated with magnesium toxicity were noted during the course of therapy. Magnesium sulfate should be considered as a potential adjunct therapy in the management of spastic paralysis caused by severe tetanus in dogs. PMID- 22316202 TI - Cholinergic crisis after neostigmine administration in a dog with acquired focal myasthenia gravis. AB - OBJECTIVE: To describe the presentation and successful management of a dog experiencing a cholinergic crisis after neostigmine administration. CASE SUMMARY: An 18-month-old neutered male Maltese-crossbred dog was diagnosed with acquired focal myasthenia gravis based on history and clinical signs of dysphagia and regurgitation, multiple series of thoracic radiographs showing focal to generalized megaesophagus, and an increased acetylcholine receptor antibody titer. After this diagnosis, the dog was initially treated with a single oral dose of pyridostigmine and later injectable neostigmine due to difficulty swallowing. Within 15 minutes of receiving a single dose (0.05 mg/kg) of subcutaneous neostigmine, the dog began showing muscarinic cholinergic signs of salivation and defecation, which progressed to nicotinic cholinergic signs of weakness and tachypnea. Within 30 minutes the dog experienced respiratory arrest and required ventilation. After 16 hours of ventilation, the dog recovered uneventfully and subsequently achieved a clinical and serologic remission from myasthenia gravis without further treatment. NEW OR UNIQUE INFORMATION PROVIDED: Cholinergic crisis and differentiation from a myasthenic crisis is described in the human literature. This case represents the first report in the veterinary literature of a cholinergic crisis in a dog treated with neostigmine. PMID- 22316203 TI - Nonsurgical pneumoperitoneum in a dog secondary to blunt force trauma to the chest. AB - OBJECTIVE: To describe the medical management of pneumoperitoneum without surgical intervention in a dog that sustained blunt force trauma to the thorax. To review the mechanisms of how a thoracic injury (ie, extra-abdominal source) can lead to pneumoperitoneum. CASE SUMMARY: A 4-month-old Shih Tzu puppy was attacked by a larger dog and sustained various injuries including a pneumothorax, pneumomediastinum, and a pneumoperitoneum. The dog presented minimally responsive and in respiratory distress secondary to pulmonary contusions and noncardiogenic pulmonary edema. No penetrating wounds to the abdomen or thorax were identified. As no immediate surgical lesion was identified the dog was treated conservatively without the need for surgical intervention. The dog was successfully managed and discharged after a few days of supportive care with oxygen therapy. Before discharge, repeat radiographs revealed complete resolution of the pneumothorax, pneumomediastinum, and pneumoperitoneum. NEW OR UNIQUE INFORMATION PROVIDED: Cases of nonsurgical pneumoperitoneum have rarely been reported in the veterinary literature. A thoracic source of pneumoperitoneum should be considered when the suspicion of a ruptured viscus is low based on diagnostic procedures (eg, ultrasound, computed tomography, and diagnostic peritoneal lavage), in addition to physical examination (eg, lack of fever and absence of abdominal pain) and laboratory findings (eg, absence of inflammatory leukogram). PMID- 22316204 TI - Mojave toxin-type ascending flaccid paralysis after an envenomation by a Southern Pacific Rattlesnake in a dog. AB - OBJECTIVE: To describe the clinical presentation and case management of a dog that developed ascending flaccid paralysis after being envenomated by a Southern Pacific rattlesnake. CASE SUMMARY: A dog was presented after it was bitten by a Southern Pacific rattlesnake. Only mild local edema and a minor coagulapathy developed, which is atypical for the Southern Pacific envenomation where hemotoxic effects are more commonly observed. Instead, a severe, rapidly progressing, ascending flaccid paralysis leading to acute respiratory failure, consistent with Mojave toxin, was seen. The patient was treated with repeated doses of antivenin and supported with mechanical ventilation. Despite clinical improvement of the paralysis over subsequent 3 days and successful weaning off the ventilator, the dog decompensated and succumbed to acute respiratory distress syndrome. NEW OR UNIQUE INFORMATION PROVIDED: The geographic region where this envenomation occurred has a documented population of Southern Pacific rattlesnakes with Mojave toxin in their venom. To the knowledge of the authors, this is the first reported case in the veterinary literature of an ascending flaccid paralysis, consistent with Mojave toxin, developing after an envenomation by a Southern Pacific rattlesnake. PMID- 22316205 TI - Clinical safety evaluation of F(ab')2 antivenom (Crotalus durissus-Bothrops asper) administration in dogs. AB - BACKGROUND: Antivenoms consisting of selective antigen binding antibody fragments, or F(ab')(2), are becoming more popular in human and veterinary medicine, owing to their preferred kinetics, tissue distribution, and removal of the Fc binding portion of IgG. Consequences of antivenom administration can include acute and delayed reactions, dependent, in part, on the antivenom's donor source, purity, and composition. This study evaluated an equine-derived polyvalent F(ab')(2) pit viper antivenom in healthy dogs of various size, age, and breed under controlled conditions. Dogs were allocated into 6 treatment groups (n = 10 per group) based on weight (3 weight groups) and dose (2 dose groups) and administered F(ab')(2) antivenom over 1 hour by IV infusion. Dogs were observed for adverse events at 3, 6, 12, and 24 hours after administration and blood was collected for CBC and serum biochemistry before and at 24 hours postadministration. KEY FINDINGS: No abnormalities were noted in the 3-vial group. In the 6-vial group, 3 dogs developed mild self-limiting edema around the head or neck, suggestive of a type 1 hypersensitivity, while another dog vomited and developed mild hypocalcemia at 24 hours, reflecting a 13% reaction rate at high doses. However, no dogs exhibited clinical signs of hypocalcemia or had any severe adverse events. CBC remained normal in all groups. SIGNIFICANCE: This study demonstrated that the polyvalent F(ab')(2) pit viper antivenom is well tolerated in dogs given large doses in a short period of time. PMID- 22316207 TI - Update on alisporivir in treatment of viral hepatitis C. AB - INTRODUCTION: There are two classes of anti-hepatitis C virus (HCV) agents currently in development: direct-acting antivirals (DAA) and host-targeting antivirals (HTA). Cyclophilin inhibitor alisporivir (ALV) , previously known as Debio-025 is the most advanced HTA in development. AREAS COVERED: Experimental and clinical studies demonstrated that ALV has high genetic barrier and no cross resistance to DAA. Pharmacokinetic studies showed a profile suitable for once daily administration. Phase I and II studies confirmed strong HCV suppression and that addition of ALV to pegylated IFNalpha (PegIFNalpha) and ribavirin (RBV) can improve their efficacy significantly. ALV was well tolerated and prevalence of the most frequent clinical and laboratory adverse events was similar to PegIFNalpha/RBV. Hyperbilirubinemia was the only significant adverse event related to ALV, but it was transient, reversible and not associated with hepatotoxicity or cholestasis. EXPERT OPINION: ALV is pangenotypic, with once daily administration and safe, therefore medication can be easy and flexible. There is still a need of data in difficult-to-treat populations and genetic studies allowing selection of possible non-responders. Registration of ALV for IFN-based treatment is expected within 3 years, but ALV is also a good candidate for IFN-sparing combinations with DAA. PMID- 22316208 TI - Subjective sleep quality in premenstrual syndrome. AB - Premenstrual syndrome (PMS) is a cyclical disorder observed in late luteal phase and presenting with behavioral changes that can affect interpersonal relationships and normal daily activity. Sleep disturbances are also common. The aim of this study is to investigate the relationship between PMS and subjective sleep quality with Pitsburg Sleep Quality Index (PSQI) in the Medical Academy students, whom have considerable information about menstruation. PMS was detected with "Premenstrual Syndrome Scale", and PSQI was used to evaluate subjective sleep quality. Chi-square test and Kendall's rank correlation analysis were used in statistical analysis. p values (p < 0.05) were considered as statistical significant. Poor sleep quality was found in the 75.6% of the participants with PMS, and 58.8% of the participants without PMS (p < 0.05). Only component 5 (sleep disorder component) of the PSQI components revealed statistically significant difference (1.7 +/- 0.6 in participants with PMS, and 1.5 +/- 0.6 without PMS, p < 0.05). There was a positive correlation between total PSQI score and all of its' components, except component 6 (sleeping pill usage component) (p < 0.05). The strongest association was found to be in the component 5 (r = 0.528; p = 0.0001). Results of our study suggested the poor sleep quality due to sleep disorders in women with PMS. PMID- 22316209 TI - Defining the molecular signature of chemotherapy-mediated lung tumor phenotype modulation and increased susceptibility to T-cell killing. AB - Chemotherapy with platinum doublets, including cisplatin plus vinorelbine, is standard of care for non-small-cell lung cancer. Sublethal exposure to certain chemotherapeutic agents has been demonstrated to alter the phenotype or biology of human tumor cells, rendering them more susceptible to cytotoxic T lymphocyte (CTL)-mediated lysis. The effects of cisplatin/vinorelbine on tumor sensitivity to T-cell cytotoxicity and its molecular mechanisms, however, have not been fully elucidated. We examined the effect of this chemotherapy on growth, cell-surface phenotype, and CTL-mediated lysis of five distinct human lung carcinoma cell lines in vitro and examined the molecular mechanisms associated with enhanced CTL sensitivity. These studies demonstrate that sublethal exposure of human lung tumor cells to the platinum doublet modulates tumor cell phenotype and increases sensitivity to major histocompatibility complex-restricted perforin/granzyme mediated CTL killing. These studies also demonstrate that exposure to chemotherapy markedly decreased the protein secretion ratio of transforming growth factor-beta/interleukin (IL)-8. We examined the gene expression profile of two lung tumor cell lines to identify a shared gene signature in response to sublethal cisplatin/vinorelbine and found coordinate expression of only 16 transcripts, including those for cytokine/chemokine expression and apoptosis such as tumor necrosis factor-alpha, IL8, CXCL5, and B cell lymphoma-2-like genes (BCL 2). Overall, these results suggest that sublethal exposure to cisplatin/vinorelbine increases sensitivity to perforin/granzyme-mediated CTL killing by modulation of (a) tumor phenotype, (b) cytokine/chemokine milieu, and (c) the proapoptotic/antiapoptotic gene ratio. The data presented here propose a complex mechanism that is distinct from and complementary to that of immunogenic cell death. This molecular signature may be useful in predicting responses to immunotherapy as well as provide the rationale for the potential clinical benefit of the combined use of vaccine with cisplatin/vinorelbine regimens. PMID- 22316210 TI - Optimal length scales emerging from shear load transfer in natural materials: application to carbon-based nanocomposite design. AB - Numerous theoretical and experimental studies on various species of natural composites, such as nacre in abalone shells, collagen fibrils in tendon, and spider silk fibers, have been pursued to provide insight into the synthesis of novel bioinspired high-performance composites. However, a direct link between the mechanical properties of the constituents and the various geometric features and hierarchies remains to be fully established. In this paper, we explore a common denominator leading to the outstanding balance between strength and toughness in natural composite materials. We present an analytical model to link the mechanical properties of constituents, their geometric arrangement, and the chemistries used in their lateral interactions. Key critical overlap length scales between adjacent reinforcement constituents, which directly control strength and toughness of composite materials, emerge from the analysis. When these length scales are computed for three natural materials-nacre, collagen molecules, and spider silk fibers-very good agreement is found as compared with experimental measurements. The model was then used to interpret load transfer capabilities in synthetic carbon-based materials through parametrization of in situ SEM shear experiments on overlapping multiwall carbon nanotubes. PMID- 22316211 TI - Cervical cancer cell lines expressing NKG2D-ligands are able to down-modulate the NKG2D receptor on NKL cells with functional implications. AB - BACKGROUND: Cervical cancer represents the third most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths in women worldwide. Natural killer (NK) cells play an important role in the defense against viruses, intracellular bacteria and tumors. NKG2D, an activating receptor on NK cells, recognizes MHC class I chain-related molecules, such as MICA/B and members of the ULBP/RAET1 family. Tumor-derived soluble NKG2D-ligands have been shown to down modulate the expression of NKG2D on NK cells. In addition to the down-modulation induced by soluble NKG2D-ligands, it has recently been described that persistent cell-cell contact can also down-modulate NKG2D expression. The goal of this study was to determine whether the NKG2D receptor is down-modulated by cell-cell contact with cervical cancer cells and whether this down-modulation might be associated with changes in NK cell activity. RESULTS: We demonstrate that NKG2D expressed on NKL cells is down-modulated by direct cell contact with cervical cancer cell lines HeLa, SiHa, and C33A, but not with non-tumorigenic keratinocytes (HaCaT). Moreover, this down-modulation had functional implications. We found expression of NKG2D-ligands in all cervical cancer cell lines, but the patterns of ligand distribution were different in each cell line. Cervical cancer cell lines co-cultured with NKL cells or fresh NK cells induced a marked diminution of NKG2D expression on NKL cells. Additionally, the cytotoxic activity of NKL cells against K562 targets was compromised after co-culture with HeLa and SiHa cells, while co-culture with C33A increased the cytotoxic activity of the NKL cells. CONCLUSIONS: Our results suggest that differential expression of NKG2D-ligands in cervical cancer cell lines might be associated with the down modulation of NKG2D, as well as with changes in the cytotoxic activity of NKL cells after cell-cell contact with the tumor cells. PMID- 22316213 TI - Multi-responsive properties of a poly(ethylene glycol)-grafted alternating copolymers of distyrenic monomer with maleic anhydride. AB - A series of amphiphilic copolymers were synthesized by reversible addition fragmentation chain transfer cyclocopolymerization of a styrenic monomer with maleic anhydride followed by grafting methoxy poly(ethylene glycol) onto the anhydride groups of the polymer chain. These amphiphilic graft copolymers exhibit multiple responsiveness toward temperature, pH, and selected cations in aqueous solutions. The cloud points (CP) of the graft copolymers increase with increasing length of the side chains and with increasing pH value of the solution. The addition of KCl and LiCl to the solutions had a salting-out effect lowering the CPs of the graft copolymers. The addition of NaCl, however, first raised the CP due to the complexation of the crown ether with Na(+) and then lowered the CP. The light scattering results confirmed an increase in phase transition temperature at lower concentrations of NaCl (5 and 10 mM) and then a decrease at a higher concentration of the sodium salt (100 mM). PMID- 22316214 TI - School screening and parental reminders in increasing dental care for children in need: a retrospective cohort study. AB - OBJECTIVE: The objective of this study is to assess follow-up dental care received by children given baseline screening and referrals as part of an ongoing clinical trial. METHODS: A retrospective study with two cohorts of kindergarten children who had baseline and follow-up (9 months later) dental exams was used. The parents/caregivers of children with routine restorative or urgent needs at baseline received a referral letter and telephone reminders to seek care for their child. Children with referrals were evaluated at follow-up exam for the receipt of care. A baseline caregiver questionnaire provided information on the individual and family characteristics of the children. RESULTS: A total of 303 children had dental exams at both time periods. At baseline, 42 percent (126/303) received referrals and among the referred group19 percent (24/126) received follow-up care. A greater proportion with urgent referrals (10/30, 33 percent) received care than those with routine referrals (14/96, 15 percent). Baseline dmft decayed, missing, filled primary teeth and DMFT decayed, missing, filled permanent teeth was similar between children who did/did not receive follow-up care (P = 0.178 and 0.491, respectively). Children receiving referrals had caregivers with less education, higher Medicaid participation, fewer routine care visits, poorer self-rating of teeth, and a higher proportion of children reporting tooth pain. Children without receipt of follow-up care had caregivers who were more likely to report not visiting a dentist within the last 5 years and a greater number of missed days from work because of tooth problems. CONCLUSION: The rate of dental utilization was low even with school screening, referral and parental reminders among poor, largely minority inner-city kindergarten children. PMID- 22316215 TI - Can SPME fiber and Tenax methods predict the bioavailability of biotransformed insecticides? AB - Recent studies recognize the ability of chemical techniques such as solid phase microextraction (SPME) fibers and Tenax extraction to predict bioavailability more effectively than exhaustive chemical extractions for sediment-associated organic contaminants. While the majority of research using these techniques studied legacy compounds such as PCBs and PAHs, there is great potential for these methods to work well for highly toxic, rapidly biotransformed compounds such as pyrethroid insecticides. The current study compared the ability of the two techniques to predict the bioavailability of permethrin and bifenthrin to two benthic invertebrates (Lumbriculus variegatus and Hexagenia sp.). In addition, variations in the application of the two techniques, specifically duration and conditions of exposure of the SPME fibers and duration of extraction with Tenax, were explored. The SPME fiber concentrations correlated strongly to both 6 and 24 h Tenax concentrations. The SPME fiber concentrations and 6 h and 24 h Tenax extractable concentrations correlated with both the parent permethrin and bifenthrin concentrations in the tissues of both species at steady state. Parent compound tissue concentrations for both species could be predicted with a single relationship for individual pyrethroids. This demonstrated the potential value of these methods to predict the bioavailability of compounds subject to biotransformation and application to multiple species. PMID- 22316216 TI - Asymmetric synthesis of Wieland-Miescher and Hajos-Parrish ketones catalyzed by an amino-acid-derived chiral primary amine. AB - This paper describes a simple chiral primary amine-catalyzed highly efficient and practical protocol for the synthesis of both Wieland-Miescher ketone and Hajos Parrish ketone as well as their analogues. The reaction can be conducted in gram scale with 1% mol catalyst loading producing high enantioselectivity (up to 96% ee) and excellent yields (up to 98%). This procedure represents one of the most efficient methods for the synthesis of these versatile chiral building blocks. PMID- 22316217 TI - Improving upon nature: active site remodeling produces highly efficient aldolase activity toward hydrophobic electrophilic substrates. AB - The substrate specificity of enzymes is frequently narrow and constrained by multiple interactions, limiting the use of natural enzymes in biocatalytic applications. Aldolases have important synthetic applications, but the usefulness of these enzymes is hampered by their narrow reactivity profile with unnatural substrates. To explore the determinants of substrate selectivity and alter the specificity of Escherichia coli 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase, we employed structure-based mutagenesis coupled with library screening of mutant enzymes localized to the bacterial periplasm. We identified two active site mutations (T161S and S184L) that work additively to enhance the substrate specificity of this aldolase to include catalysis of retro-aldol cleavage of (4S) 2-keto-4-hydroxy-4-(2'-pyridyl)butyrate (S-KHPB). These mutations improve the value of k(cat)/K(M)(S-KHPB) by >450-fold, resulting in a catalytic efficiency that is comparable to that of the wild-type enzyme with the natural substrate while retaining high stereoselectivity. Moreover, the value of k(cat)(S-KHPB) for this mutant enzyme, a parameter critical for biocatalytic applications, is 3-fold higher than the maximal value achieved by the natural aldolase with any substrate. This mutant also possesses high catalytic efficiency for the retro aldol cleavage of the natural substrate, KDPG, and a >50-fold improved activity for cleavage of 2-keto-4-hydroxy-octonoate, a nonfunctionalized hydrophobic analogue. These data suggest a substrate binding mode that illuminates the origin of facial selectivity in aldol addition reactions catalyzed by KDPG and 2-keto-3 deoxy-6-phosphogalactonate aldolases. Furthermore, targeting mutations to the active site provides a marked improvement in substrate selectivity, demonstrating that structure-guided active site mutagenesis combined with selection techniques can efficiently identify proteins with characteristics that compare favorably to those of naturally occurring enzymes. PMID- 22316218 TI - Assessment of the average price and ethanol content of alcoholic beverages by brand--United States, 2011. AB - BACKGROUND: There are no existing data on alcoholic beverage prices and ethanol (EtOH) content at the level of alcohol brand. A comprehensive understanding of alcohol prices and EtOH content at the brand level is essential for the development of effective public policy to reduce alcohol use among underage youth. The purpose of this study was to comprehensively assess alcoholic beverage prices and EtOH content at the brand level. METHODS: Using online alcohol price data from 15 control states and 164 online alcohol stores, we estimated the average alcohol price and percent alcohol by volume for 900 brands of alcohol, across 17 different alcoholic beverage types, in the United States in 2011. RESULTS: There is considerable variation in both brand-specific alcohol prices and EtOH content within most alcoholic beverage types. For many types of alcohol, the within-category variation between brands exceeds the variation in average price and EtOH content among the several alcoholic beverage types. Despite differences in average prices between alcoholic beverage types, in 12 of the 16 alcoholic beverage types, customers can purchase at least 1 brand of alcohol that is under $1 per ounce of EtOH. CONCLUSIONS: Relying on data or assumptions about alcohol prices and EtOH content at the level of alcoholic beverage type is insufficient for understanding and influencing youth drinking behavior. Surveillance of alcohol prices and EtOH content at the brand level should become a standard part of alcohol research. PMID- 22316219 TI - Discovery and description of a new trichostrongyloid species (Nematoda: Ostertagiinae), abomasal parasites in mountain goat, Oreamnos americanus, from the Western Cordillera of North America. AB - Marshallagia lichtenfelsi sp. n. is a dimorphic ostertagiine nematode occurring in the abomasum of mountain goats, Oreamnos americanus, from the Western Cordillera of North America. Major and minor morphotype males and females are characterized and distinguished relative to the morphologically similar Marshallagia marshalli / Marshallagia occidentalis from North America and Marshallagia dentispicularis, along with other congeners, from the Palearctic region. The configuration of the convoluted and irregular synlophe in the cervical region of males and females of M. lichtenfelsi is apparently unique, contrasting with a continuous and parallel system of ridges among those species of Marshallagia, including M. marshalli/M. occidentalis, which have been evaluated. Specimens of M. lichtenfelsi are further defined by the rectangular form of the accessory bursal membrane (width > length) in the major morphotype and by the trapezoidal Sjoberg's organ in the minor morphotype, in addition to specific attributes of the spicules and spicule tips. We regard 12 species, including the proposed new taxon, to be valid. Primary diagnostic characters are reviewed for Marshallagia and a framework is presented for standardization of future descriptions incorporating the synlophe in males and females and the structure of the spicules and genital cone in major and minor morphotype males. The center of diversity for species of Marshallagia is the mountain-steppe region of central Eurasia where 11 species (including the Holarctic M. marshalli) are recognized in association with Caprini, Rupicaprini, and Antelopinae; only 2 species occur in the Nearctic. In this assemblage, M. lichtenfelsi is endemic to North America and limited in host distribution to mountain goats. An intricate history for refugial isolation and population fragmentation demonstrated for mountain goats and wild sheep indicates the potential for considerable cryptic diversity for Marshallagia and other nematodes. Shifting patterns of contact and sympatry among assemblages of ungulates during the Pleistocene are consistent with geographic and host colonization as a process involved in diversification of these parasites. PMID- 22316220 TI - Fibrin-based model for cartilage regeneration: tissue maturation from in vitro to in vivo. AB - One of the crucial points for a successful tissue-engineering approach for cartilage repair is represented by the level of in vitro maturation of the engineered tissue before implantation. The purpose of this work was to evaluate the effect of the level of in vitro maturation of engineered cartilaginous samples on the tissue quality after in vivo implantation. Samples were obtained from isolated swine articular chondrocytes embedded in fibrin glue. The cell fibrin composites were either cultured in vitro or directly implanted in vivo for 1, 5, and 9 weeks. Other experimental samples were precultured for either 1 or 5 weeks in vitro and then implanted in vivo for 4 additional weeks. All the samples were analyzed by histology, immunohistochemistry, biochemistry, and gene expression. The results strongly suggest that the in vivo culture in this model promoted a better tissue maturation than that obtained in the in vitro condition, and that 1 week in vitro preculture resulted in the primary structuring of the engineered composites and their subsequent maturation in vivo, without affecting the cell viability and activity, while a prolonged in vitro preculture caused a cell and matrix degeneration that could not be rescued in vivo. PMID- 22316222 TI - Timing of first dental checkup for newly Medicaid-enrolled children with an intellectual or developmental disability. AB - We compared the extent to which having an intellectual or developmental disability was associated with rates at which Iowa Medicaid-enrolled children ages 3 to 8 had first dental checkups after an initial dental examination. We hypothesized that these children would have later first dental checkups than would children without an intellectual or developmental disability. Findings suggest no significant difference in the time to first dental checkup for children by intellectual or developmental disability status. Those who took over 12 months to see a dentist for their initial dental examination were 1.68 times as likely to have an earlier first dental checkup as children whose initial dental examination occurred within 4 months of being enrolled. Results suggest that having an intellectual or developmental disability is not associated with later first dental checkups for this population. PMID- 22316223 TI - Transition planning for students with intellectual disability, autism, or other disabilities: data from the National Longitudinal Transition Study-2. AB - To compare the status of transition planning for students with intellectual disability, autism, or other disabilities, we used data from the National Longitudinal Transition Study-2, a federally funded, national study of the secondary and postschool experiences of students with disabilities. Results show that although transition planning had been conducted for the majority of students, few of them took a leadership role in their transition planning. Students with autism or intellectual disability were significantly less likely than students with other disabilities to take a leadership role. The majority of the active participants in transition planning were school-based personnel. We also found limited participation from other agencies/support persons (e.g., vocational rehabilitation). Students with autism or intellectual disability had more identified needs for support after school than did students with other disabilities. PMID- 22316224 TI - Factors associated with self-concept: adolescents with intellectual and development disabilities share their perspectives. AB - How one perceives the self is critical to long-term development. The purpose of this study was to explore the self-perceptions of adolescents with intellectual and developmental disabilities. Participants included 51 adolescents with intellectual and developmental disabilities, their parents (n = 50), and teachers (n = 12). A mixed-methods design was used. Qualitative interviews revealed that although 55% of participants self-identified as having a disability, there was a lack of constructive or affirmative language used to describe disability. Overall, adolescents' understanding of disability appeared to be grounded in a deficit model. Quantitative analyses were used to explore demographic variables, adolescent' perception of parent support, and self determination as possible predictors of global self-worth and social acceptance. Results indicate that family income and parent support are particularly salient for this population. PMID- 22316225 TI - Sleep problems and early developmental delay: implications for early intervention programs. AB - Sleep disorders negatively impact behavior, cognition, and growth--the same areas targeted by early intervention. Conversely, developmental delays and disabilities may themselves precipitate sleep disorders. Young children with developmental delays experience sleep disorders at a higher rate than do typically developing children; the most common types are difficulties initiating or maintaining sleep and sleep disordered breathing. To date, attention has been focused on sleep problems in children with specific conditions (e.g., autism, genetic syndromes, prematurity, and seizure disorder). The authors review evidence of sleep problems' broader impact across the range of children screened for early intervention. Eligibility evaluations for early intervention address the five developmental domains: adaptive, motor, cognitive, communication, and socioemotional. Disordered sleep may be symptomatic of socioemotional and adaptive problems. Assessing sleep problems within the evaluation may help establish eligibility for early intervention services and would maximize developmental potential by ensuring timely identification, referral, and treatment. PMID- 22316226 TI - Self-report computer-based survey of technology use by people with intellectual and developmental disabilities. AB - Advancements of technologies in the areas of mobility, hearing and vision, communication, and daily living for people with intellectual and developmental disabilities has the potential to greatly enhance independence and self determination. Previous research, however, suggests that there is a technological divide with regard to the use of such technologies by people with intellectual and developmental disabilities when compared with the use reported by the general public. To provide current information with regard to technology use by people with intellectual and developmental disabilities by examining the technology needs, use, and barriers to such use experienced by 180 adults with intellectual and developmental disabilities, we used QuestNet, a self-directed computer survey program. Results suggest that although there has been progress in technology acquisition and use by people with intellectual and developmental disabilities, an underutilization of technologies across the population remains. PMID- 22316227 TI - Employment and self-management: a meta-evaluation of seven literature reviews. AB - Efforts focused on teaching individuals with intellectual disabilities to manage their own affairs have evolved over the past 30 years. Self-management strategies, in particular, hold much promise when the goal is to promote self determination. In this article, the authors describe trends in the evolution of self-management strategies by analyzing seven literature reviews. The authors conclude with thoughts related to jump-starting an intervention that has appeared to lose momentum, namely, self-management. PMID- 22316230 TI - A program design for full integration and assessment of clinically relevant interprofessional education into the clinical/clerkship year for nursing and medical students. PMID- 22316231 TI - The value of a quality improvement project in promoting interprofessional collaboration. AB - The teamwork that is required for interprofessional collaboration in healthcare is not an inherent attribute of the current system, and must be fostered. Education, training, and role modelling are important enablers. From our experience we posit that participating in a quality improvement project can be also be an excellent vehicle to promote interprofessional collaboration. PMID- 22316234 TI - Current epidemiological profile and features of visceral leishmaniasis in people's republic of China. AB - BACKGROUND: Visceral leishmaniasis (VL) is still an important public health problem in China. In recent years endemic regions spread, prevalence increased, and even an outbreak of the disease occurred in China due to global warming and population movement. It is essential to elucidate the current epidemic situation and epidemiological characteristics of VL for designing control policy. In the present study we describe the current epidemiological profile and characteristics of VL in China based on retrospectively reviewing of VL cases reported between 2005 and 2010 by a passive surveillance system. METHODS: The present study was a retrospective review of VL cases notified between 2005 and 2010 based on the passive surveillance data. The data were tabulated, diagrammatized and analyzed through descriptive statistics in a Microsoft Excel spreadsheet. RESULTS: A total of 2450 VL cases were notified, with a mean of 408 cases per year. 61 counties were identified as endemic area with 2224 autochthonous cases, and the other 118 counties as non-endemic areas with 226 imported cases. 97.71% of cases were concentrated in Xinjiang, Gansu and Sichuan Provinces. 9 major counties reported a mean of > 10 cases per year, with a total of 1759 cases reported. Different types of VL revealed distinct epidemiological characteristics. CONCLUSIONS: The number of VL cases and endemic counties both increased in the period 2005-2010 in China. Different type or sub-type of VL revealed distinct epidemiological characteristics. Therefore, differential control measures must be taken in different endemic areas against incidence increase and endemic area spread. PMID- 22316235 TI - Bilateral step length estimation using a single inertial measurement unit attached to the pelvis. AB - BACKGROUND: The estimation of the spatio-temporal gait parameters is of primary importance in both physical activity monitoring and clinical contexts. A method for estimating step length bilaterally, during level walking, using a single inertial measurement unit (IMU) attached to the pelvis is proposed. In contrast to previous studies, based either on a simplified representation of the human gait mechanics or on a general linear regressive model, the proposed method estimates the step length directly from the integration of the acceleration along the direction of progression. METHODS: The IMU was placed at pelvis level fixed to the subject's belt on the right side. The method was validated using measurements from a stereo-photogrammetric system as a gold standard on nine subjects walking ten laps along a closed loop track of about 25 m, varying their speed. For each loop, only the IMU data recorded in a 4 m long portion of the track included in the calibrated volume of the SP system, were used for the analysis. The method takes advantage of the cyclic nature of gait and it requires an accurate determination of the foot contact instances. A combination of a Kalman filter and of an optimally filtered direct and reverse integration applied to the IMU signals formed a single novel method (Kalman and Optimally filtered Step length Estimation - KOSE method). A correction of the IMU displacement due to the pelvic rotation occurring in gait was implemented to estimate the step length and the traversed distance. RESULTS: The step length was estimated for all subjects with less than 3% error. Traversed distance was assessed with less than 2% error. CONCLUSIONS: The proposed method provided estimates of step length and traversed distance more accurate than any other method applied to measurements obtained from a single IMU that can be found in the literature. In healthy subjects, it is reasonable to expect that, errors in traversed distance estimation during daily monitoring activity would be of the same order of magnitude of those presented. PMID- 22316236 TI - The magnitude and trend of artemether-lumefantrine stock-outs at public health facilities in Kenya. AB - BACKGROUND: Health facility stock-outs of artemether-lumefantrine (AL), the common first-line therapy for uncomplicated malaria across Africa, adversely affect effective malaria case-management. They have been previously reported on various scales in time and space, however the magnitude of the problem and trends over time are less clear. Here, 2010-2011 data are reported from public facilities in Kenya where alarming stock-outs were revealed in 2008. METHODS: Data were collected between January 2010 and June 2011 as part of 18 monthly cross-sectional surveys undertaken at nationally representative samples of public health facilities. The primary monitoring indicator was total stock-out of all four weight-specific AL packs. The secondary indicators were stock-outs of at least one AL pack and individual stock-outs for each AL pack. Monthly proportions and summary means of the proportions over the monitoring period were measured for each indicator. Stock-out trends were assessed using linear regression. RESULTS: The number of surveyed facilities across 18 time points ranged between 162 and 176 facilities. The stock-out means of the proportion of health facilities were 11.6% for total AL stock-out, 40.6% for stock-out of at least one AL pack, and between 20.5% and 27.4% for stock-outs of individual AL packs. Monthly decrease of the total AL stock-out was 0.005% (95% CI: -0.5 to +0.5; p = 0.983). Monthly decrease in the stock-out of at least one AL pack was 0.7% (95% CI: -1.5 to +0.3; p = 0.058) while stock-outs of individual AL packs decreased monthly between 0.2% for AL 24-pack and 0.7% for AL six-pack without statistical significance for any of the weight-specific packs. CONCLUSIONS: Despite lower levels of AL stock-outs compared to the reports in 2008, the stock-outs at Kenyan facilities during 2010 2011 are still substantial and of particular worry for the most detrimental:- simultaneous absence of any AL pack. Only minor decrease was observed in the stock-outs of individual AL packs. Recently launched interventions to eliminate AL stock-outs in Kenya are fully justified. PMID- 22316237 TI - FRAX or fiction: determining optimal screening strategies for treatment of osteoporosis in residents in long-term care facilities. AB - OBJECTIVES: To examine screening strategies for osteoporosis and fractures for treatment of long-term care residents. DESIGN: Cross-sectional analysis to examine screening strategies for treatment. SETTING: Assisted living and skilled care facilities. PARTICIPANTS: Two hundred two frail women aged 65 and older (mean 85), excluding those receiving bisphosphonates. MEASUREMENTS: Clinical fractures of the hip or spine (Clin Fx); Clin Fx or bone mineral density (BMD); Clin Fx, BMD, or vertebral fractures (VF) assessed according to dual-energy X-ray absorptiometry-based vertebral fracture assessments; fracture risk algorithm using femoral neck BMD (FRAX-FN); fracture risk algorithm using body mass index (FRAX-BMI); or Clin Fx or heel ultrasound (heel US). RESULTS: Treatment eligibility ranged from 17% (Clin Fx) to 98% (FRAX-BMI). VFs were found in 47%, 74% of which were silent. Criteria with Clin Fx, BMD, or VF identified 73% of study participants for treatment. FRAX-FN suggested treatment in 81% but would have missed approximately 10% of individuals with silent VFs. Clin Fx or heel US suggested that 39% of participants were eligible for treatment. CONCLUSION: Long term care residents eligible for osteoporosis treatment ranged from fewer than 20% to roughly all residents depending on screening criteria. VFs are common and identify a subset of residents missed by conventional BMD scans or FRAX-FN. A reasonable clinical approach could consider treatment for those with Clin Fx of the hip or spine, radiological evidence of a VF, or osteoporosis according to BMD classification. Prospective studies are needed to determine optimal screening strategies for treatment in this cohort. PMID- 22316238 TI - The X-ray absorption spectroscopic model of the copper(II) imidazole complex ion in liquid aqueous solution: a strongly solvated square pyramid. AB - Cu K-edge extended X-ray absorption fine structure (EXAFS) and Minuit X-ray absorption near-edge structure (MXAN) analyses were combined to evaluate the structure of the copper(II) imidazole complex ion in liquid aqueous solution. Both methods converged to the same square-pyramidal inner coordination sphere [Cu(Im)(4)L(ax)](2+) (L(ax) indeterminate) with four equatorial nitrogen atoms at EXAFS, 2.02 +/- 0.01 A, and MXAN, 1.99 +/- 0.03 A. A short-axial N/O scatterer (L(ax)) was found at 2.12 +/- 0.02 A (EXAFS) or 2.14 +/- 0.06 A (MXAN). A second but very weak axial Cu-N/O interaction was found at 2.9 +/- 0.1 A (EXAFS) or 3.0 +/- 0.1 A (MXAN). In the MXAN fits, only a square-pyramidal structural model successfully reproduced the doubled maximum of the rising K-edge X-ray absorption spectrum, specifically excluding an octahedral model. Both EXAFS and MXAN also found eight outlying oxygen scatterers at 4.2 +/- 0.3 A that contributed significant intensity over the entire spectral energy range. Two prominent rising K-edge shoulders at 8987.1 and 8990.5 eV were found to reflect multiple scattering from the 3.0 A axial scatterer and the imidazole rings, respectively. In the MXAN fits, the imidazole rings took in-plane rotationally staggered positions about copper. The combined (EXAFS and MXAN) model for the unconstrained cupric imidazole complex ion in liquid aqueous solution is an axially elongated square-pyramidal core, with a weak nonbonded interaction at the second axial coordination position and a solvation shell of eight nearest-neighbor water molecules. This core square-pyramidal motif has persisted through [Cu(H(2)O)(5)](2+), [Cu(NH(3))(4)(NH(3),H(2)O)](2+), (1, 2) and now [Cu(Im)(4)L(ax))](2+) and appears to be the geometry preferred by unconstrained aqueous-phase copper(II) complex ions. PMID- 22316239 TI - Natural products as sources of new drugs over the 30 years from 1981 to 2010. AB - This review is an updated and expanded version of the three prior reviews that were published in this journal in 1997, 2003, and 2007. In the case of all approved therapeutic agents, the time frame has been extended to cover the 30 years from January 1, 1981, to December 31, 2010, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2010 for all approved antitumor drugs worldwide. We have continued to utilize our secondary subdivision of a "natural product mimic" or "NM" to join the original primary divisions and have added a new designation, "natural product botanical" or "NB", to cover those botanical "defined mixtures" that have now been recognized as drug entities by the FDA and similar organizations. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, over the time frame from around the 1940s to date, of the 175 small molecules, 131, or 74.8%, are other than "S" (synthetic), with 85, or 48.6%, actually being either natural products or directly derived therefrom. In other areas, the influence of natural product structures is quite marked, with, as expected from prior information, the anti-infective area being dependent on natural products and their structures. Although combinatorial chemistry techniques have succeeded as methods of optimizing structures and have been used very successfully in the optimization of many recently approved agents, we are able to identify only one de novo combinatorial compound approved as a drug in this 30-year time frame. We wish to draw the attention of readers to the rapidly evolving recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the "host from whence it was isolated", and therefore we consider that this area of natural product research should be expanded significantly. PMID- 22316240 TI - UV-induced bursting of cell-sized multicomponent lipid vesicles in a photosensitive surfactant solution. AB - We study the behavior of multicomponent giant unilamellar vesicles (GUVs) in the presence of AzoTAB, a photosensitive surfactant. GUVs are made of an equimolar ratio of dioleoylphosphatidylcholine (DOPC) and dipalmitoylphosphatidylcholine (DPPC) and various amounts of cholesterol (Chol), where the lipid membrane shows a phase separation into a DPPC-rich liquid-ordered (L(o)) phase and a DOPC-rich liquid-disordered (L(d)) phase. We find that UV illumination at 365 nm for 1 s induces the bursting of a significant fraction of the GUV population. The percentage of UV-induced disrupted vesicles, called bursting rate (Y(burst)), increases with an increase in [AzoTAB] and depends on [Chol] in a non-monotonous manner. Y(burst) decreases when [Chol] increases from 0 to 10 mol % and then increases with a further increase in [Chol], which can be correlated with the phase composition of the membrane. We show that Y(burst) increases with the appearance of solid domains ([Chol] = 0) or with an increase in area fraction of L(o) phase (with increasing [Chol] >= 10 mol %). Under our conditions (UV illumination at 365 nm for 1 s), maximal bursting efficiency (Y(burst) = 53%) is obtained for [AzoTAB] = 1 mM and [Chol] = 40 mol %. Finally, by restricting the illumination area, we demonstrate the first selective UV-induced bursting of individual target GUVs. These results show a new method to probe biomembrane mechanical properties using light as well as pave the way for novel strategies of light-induced drug delivery. PMID- 22316241 TI - Synthesis of polysubstituted, functionalized quinolines through a metal-free domino process involving a C4-C3 functional group rearrangement. AB - 4-Alkyl-1,2,3,4-tetrahydroquinolines bearing a 4-vinyl unit ending in an electron withdrawing group were efficiently transformed into polysubstituted, C(3) functionalized quinolines upon heating in refluxing o-dichlorobenzene, in a domino reaction involving an unusual C(4)-C(3) functional group rearrangement. PMID- 22316242 TI - The significance of floaters in the nicks of Mohs frozen sections. PMID- 22316244 TI - Activation of proteolytic enzymes and depression of the sarcolemmal Na+/K+-ATPase in ischemia-reperfused heart may be mediated through oxidative stress. AB - We tested whether the activation of proteolytic enzymes, calpain, and matrix metalloproteinases (MMPs) during ischemia-reperfusion (I/R) is mediated through oxidative stress. For this purpose, isolated rat hearts were subjected to a 30 min global ischemia followed by a 30 min reperfusion. Cardiac function was monitored and the activities of Na(+)/K(+)-ATPase, Mg(2+)-ATPase, calpain, and MMP were measured. Depression of cardiac function and Na(+)/K(+)-ATPase activity in I/R hearts was associated with increased calpain and MMP activities. These alterations owing to I/R were similar to those observed in hearts perfused with hypoxic medium, H(2)O(2) and xanthine plus xanthine oxidase. The I/R-induced changes were attenuated by ischemic preconditioning as well as by perfusing the hearts with N-acetylcysteine or mercaptopropionylglycine. Inhibition of MMP activity in hearts treated with doxycycline depressed the I/R-induced changes in cardiac function and Na(+)/K(+)-ATPase activity without affecting the calpain activation. On the other hand, inhibition of calpain activity upon treatment with leupeptin or MDL 28170 significantly reduced the MMP activity in addition to attenuating the I/R-induced alterations in cardiac function and Na(+)/K(+)-ATPase activity. These results suggest that the I/R-induced depression in Na(+)/K(+) ATPase and cardiac function may be a consequence of the increased activities of both calpain and MMP because of oxidative stress in the heart. PMID- 22316245 TI - Noncovalent assembly of targeted carbon nanovectors enables synergistic drug and radiation cancer therapy in vivo. AB - Current chemotherapeutics are characterized by efficient tumor cell-killing and severe side effects mostly derived from off-target toxicity. Hence targeted delivery of these drugs to tumor cells is actively sought. In an in vitro system, we previously demonstrated that targeted drug delivery to cancer cells overexpressing epidermal growth factor receptor (EGFR+) can be achieved by poly(ethylene glycol)-functionalized carbon nanovectors simply mixed with a drug, paclitaxel, and an antibody that binds to the epidermal growth factor receptor, cetuximab. This construct is unusual in that all three components are assembled through noncovalent interactions. Here we show that this same construct is effective in vivo, enhancing radiotherapy of EGFR+ tumors. This targeted nanovector system has the potential to be a new therapy for head and neck squamous cell carcinomas, deserving of further preclinical development. PMID- 22316246 TI - Genome sequence of Desulfitobacterium hafniense DCB-2, a Gram-positive anaerobe capable of dehalogenation and metal reduction. AB - BACKGROUND: The genome of the Gram-positive, metal-reducing, dehalorespiring Desulfitobacterium hafniense DCB-2 was sequenced in order to gain insights into its metabolic capacities, adaptive physiology, and regulatory machineries, and to compare with that of Desulfitobacterium hafniense Y51, the phylogenetically closest strain among the species with a sequenced genome. RESULTS: The genome of Desulfitobacterium hafniense DCB-2 is composed of a 5,279,134-bp circular chromosome with 5,042 predicted genes. Genome content and parallel physiological studies support the cell's ability to fix N2 and CO2, form spores and biofilms, reduce metals, and use a variety of electron acceptors in respiration, including halogenated organic compounds. The genome contained seven reductive dehalogenase genes and four nitrogenase gene homologs but lacked the Nar respiratory nitrate reductase system. The D. hafniense DCB-2 genome contained genes for 43 RNA polymerase sigma factors including 27 sigma-24 subunits, 59 two-component signal transduction systems, and about 730 transporter proteins. In addition, it contained genes for 53 molybdopterin-binding oxidoreductases, 19 flavoprotein paralogs of the fumarate reductase, and many other FAD/FMN-binding oxidoreductases, proving the cell's versatility in both adaptive and reductive capacities. Together with the ability to form spores, the presence of the CO2 fixing Wood-Ljungdahl pathway and the genes associated with oxygen tolerance add flexibility to the cell's options for survival under stress. CONCLUSIONS: D. hafniense DCB-2's genome contains genes consistent with its abilities for dehalogenation, metal reduction, N2 and CO2 fixation, anaerobic respiration, oxygen tolerance, spore formation, and biofilm formation which make this organism a potential candidate for bioremediation at contaminated sites. PMID- 22316247 TI - Dental anxiety and oral health outcomes among rural older adults. AB - OBJECTIVES: The objective of this study is to determine the degree to which rural older adults are able to complete a measure of dental anxiety and to assess the prevalence, as well as the demographic and oral health characteristics, of individuals reporting high dental anxiety. METHODS: A population-based sample of 635 African American, American Indian and White older adults (age >= 60 years) completed an in-home survey, and 362 dentate participants completed an oral examination. Dental anxiety was measured using the four-item Corah's Dental Anxiety Scale (DAS). Gender, ethnicity, age, education, and oral health outcomes were compared between those who completed all four DAS questions (completers) and those who did not (noncompleters) as well as, among completers, those with high versus low DAS scores. RESULTS: There were 94 (14.8%) noncompleters. Noncompletion was associated with older age, lower education, being edentulous, and having gingival recession. 12.4% of DAS completers had high DAS scores, which was more common among those aged 60-70 years, women, and those with oral pain and sore or bleeding gums. In logistic regression analysis, only sore and bleeding gums had a significant association with a high DAS score (odds ratio = 2.40, 95% confidence interval 1.09-5.26). CONCLUSIONS: About one in eight rural older adults have high dental anxiety, which is associated with poor oral health outcomes. Identifying new approaches to measure dental anxiety among a population with limited interaction with dental care providers is needed. PMID- 22316250 TI - It's a 'kidney' not a 'renal'. PMID- 22316249 TI - Ethanol sensitivity in high drinking in the dark selectively bred mice. AB - BACKGROUND: Mouse lines are being selectively bred in replicate for high blood ethanol concentrations (BECs) achieved after a short period of ethanol (EtOH) drinking early in the circadian dark phase. High Drinking in the Dark-1 (HDID-1) mice were in selected generation S18, and the replicate HDID-2 line in generation S11. METHODS: To determine other traits genetically correlated with high DID, we compared naive animals from both lines with the unselected, segregating progenitor stock, HS/Npt. Differences between HDID-1 and HS would imply commonality of genetic influences on DID and these traits. RESULTS: HDID-1 mice showed less basal activity, greater EtOH stimulated activity, and greater sensitivity to EtOH-induced foot slips than HS. They showed lesser sensitivity to acute EtOH hypothermia and longer duration loss of righting reflex than HS. HDID 1 and control HS lines did not differ in sensitivity on 2 measures of intoxication, the balance beam and the accelerating rotarod. None of the acute response results could be explained by differences in EtOH metabolism. HDID-2 differed from HS on some, but not all, of the above responses. CONCLUSIONS: These results show that some EtOH responses share common genetic control with reaching high BECs after DID, a finding consistent with other data regarding genetic contributions to EtOH responses. PMID- 22316251 TI - Coagulation in hepatobiliary disease. AB - OBJECTIVE: To review the pathogenesis and clinical consequences of coagulation abnormalities accompanying hepatobiliary disorders and to highlight the need for further studies to characterize these derangements and their treatment options in small animal patients. DATA SOURCES: Veterinary and human medical literature: original research articles, scientific reviews, consensus statements, and recent texts. SUMMARY: The liver plays an important role in the production and clearance of many components of coagulation. A wide range of hemostatic derangements can occur in patients with hepatobiliary disease including alterations in platelet number and function, coagulation factor levels, anticoagulants, vascular endothelial function, and fibrinolysis. As these hemostatic alterations include both pro- and anticoagulation pathways, the net result is often a rebalanced hemostatic system that can be easily disrupted by concurrent conditions resulting in either clinical bleeding or thrombosis. Conventional coagulation tests are inadequate at identifying the spectrum of coagulation alterations occurring in patients with hepatobiliary disease, but their evaluation is necessary to assess bleeding risk and provide prognostic information. A paucity of information exists regarding the treatment of the coagulation derangements in small animals with hepatobiliary disease. Extrapolation from human studies provides some information about potential treatment options, but further studies are warranted in this area to elucidate the best management for coagulation abnormalities in dogs and cats with hepatobiliary disease. CONCLUSION: Hepatobiliary disease can have profound effects on coagulation function leading to hypercoagulable or hypocoagulable states. Overall coagulation status with hepatobiliary disease depends on both the type and severity of disease and the presence of associated complications. PMID- 22316253 TI - A clinical review of peritoneal dialysis. AB - OBJECTIVE: To review the principles and practice of peritoneal dialysis in veterinary medicine. DATA SOURCES: Clinical and experimental studies and current guideline recommendations from the human literature; and original case studies, case reports, and previous reviews in the veterinary literature. SUMMARY: Peritoneal dialysis involves the exchange of solutes and fluid between the peritoneal capillary blood and the dialysis solution across the peritoneal membrane. It requires placement of a peritoneal dialysis catheter for repeated dialysate exchange. The ideal catheter provides reliable, rapid dialysate flow rates without leaks or infections. Catheter selection and placement are reviewed along with dialysate selection, exchange prescriptions, and overall patient management. PD does not require specific or complex equipment, and it can achieve effective control of uremia and electrolyte imbalances. CONCLUSIONS: Peritoneal dialysis is a potential life-saving measure for patients with acute renal failure. Peritoneal dialysis results in gradual decline in uremic toxins. Previously low success rates have been reported. Improved success rates have been noted in dogs with acute kidney injury (AKI) secondary to leptospirosis. Cats also have a good success rate when PD is elected in patients with a potentially reversible underlying disease. Overall, PD remains a viable intervention for patients with AKI unresponsive to medical management. In select patients a favorable outcome is attained whereby PD provides temporary support until return of effective renal function is attained. PMID- 22316254 TI - Cardiopulmonary effects of a new inspiratory impedance threshold device in acute hemorrhagic shock in dogs. AB - OBJECTIVE: To compare cardiovascular and respiratory effects of an inspiratory impedance threshold device (ITD) in dogs before and after induction of acute hemorrhagic shock. STUDY DESIGN: Prospective experimental randomized study. ANIMALS: Eight healthy adult dogs. METHODS: Dogs were anesthetized and maintained on spontaneous ventilation. Tidal volume (V(T)), systolic, mean and diastolic arterial blood pressure (SAP, MAP, DAP), central venous pressure (CVP), gastric P(CO2) (GBF) as an indicator of gastric perfusion, cardiac index (CI), systemic vascular resistance (SVR), oxygen delivery (DO(2)), and plasma lactate were monitored. To monitor respiratory compliance (RC) and respiratory resistance (ResR), animals were briefly placed on mechanical ventilation. Dogs were studied under 4 different conditions: (1) baseline (euvolemic state) (MAP > 60 mm Hg) with and without the ITD and (2) acute hemorrhagic shock (hypovolemic state) (target MAP of 40 mm Hg) with and without ITD. These 4 conditions were performed during one anesthetic period, allowing time for stabilization of parameters for each condition. Data were analyzed by ANOVA for repeated measure mixed models. RESULTS: No cardiovascular changes were detected between groups with and without use of ITD during euvolemic states. During acute hemorrhagic hypovolemic state, CI and DO(2) were higher with the ITD (2.9 +/- 0.6 L/min/m(2)) and (326.5 +/- 86.8 mL/min) compared with no ITD (1.8 +/- 0.6 L/min/m(2)) and (191.3 +/- 58.1 mL/min), respectively. The use of ITD during hypovolemia also increased SAP and MAP. There was an increase in ResR and decreased RC with the ITD in both euvolemic and hypovolemic states. CONCLUSION AND CLINICAL RELEVANCE: The use of an ITD in dogs during acute hemorrhagic hypovolemic shock improved cardiovascular parameters but had negative effects on RC and ResR. PMID- 22316255 TI - Evaluation of coagulation status in dogs with naturally occurring canine hyperadrenocorticism. AB - OBJECTIVE: To determine whether or not there are differences in coagulation parameters (eg, thrombelastography [TEG], activated partial thromboplastin time [aPTT], prothrombin time [PT], and fibrinogen) among dogs with naturally occurring hyperadrenocorticism (HAC), dogs with HAC undergoing medical management, and dogs without HAC. DESIGN: Prospective, observational study. SETTING: Veterinary teaching hospital. ANIMALS: Forty-six client-owned dogs undergoing adrenal function testing. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nine dogs were diagnosed with HAC de novo, 19 dogs were presented for therapeutic monitoring of previously diagnosed HAC, and 18 dogs did not have HAC. Variables compared between groups were age, body weight, platelet count, mean platelet volume, serum concentrations of cholesterol, triglycerides, antithrombin, PT, aPTT, fibrinogen, and TEG parameters (eg, alpha angle, R, K, and maximum amplitude [MA]). Dogs with HAC and dogs treated for HAC had higher serum cholesterol than dogs without HAC (P < 0.05). All groups had mean MA greater than the institutional reference interval. There was a weak, positive correlation between hematocrit and MA that was independent of diagnosis (r(2) = 0.266, P = 0.004). CONCLUSIONS: The results of this study do not support the supposition that a significant difference exists in coagulation tendencies between dogs with HAC prior to treatment, dogs with HAC during treatment, and dogs without HAC. This disagreement with the classically accepted notion that HAC leads to a hypercoagulable state could be due to a couple of possibilities. Namely, the link between HAC and hypercoagulability may be relatively weak, or our findings may be the result of a type II error either as a result of a small sample size or the use of coagulation assays that are insensitive to the effects of HAC on the hemostatic system. PMID- 22316256 TI - Comparison of tissue oxygen saturation in ovariohysterectomized dogs recovering on room air versus nasal oxygen insufflation. AB - OBJECTIVE: To compare tissue oxygen saturation in ovariohysterectomized dogs recovering postoperatively on room air versus nasal oxygen insufflation. DESIGN: Prospective clinical study. SETTING: University teaching hospital. ANIMALS: Twenty dogs undergoing ovariohysterectomy. INTERVENTIONS: Dogs were randomized to breathe either room air or 100 mL/kg/min of nasal oxygen insufflation for 2 hours postoperatively. Tissue oxygen saturation (StO(2)) was evaluated at 2 mm and 20 mm lateral to the surgical incision, as well as in the inguinal region using a noninvasive tissue oximeter. MEASUREMENTS AND MAIN RESULTS: In dogs recovered on nasal oxygen insufflation (n = 10), tissue oxygen saturation was significantly higher--20 mm from the surgical site (88.44 +/- 2.50%, P = 0.02) and in the inguinal region (83.56 +/- 1.91%, P = 0.032)-- compared to dogs recovered on room air (n = 10, 79.11% +/- 2.50 and 77.12% +/- 1.91, respectively). CONCLUSIONS: In ovariohysterectomized dogs, oxygen supplementation for 2 hours postoperatively improves tissue oxygen saturation 20 mm adjacent to the linea alba and in the inguinal region. Oxygen supplementation in postoperative dogs is an inexpensive and easily applicable method to improve tissue oxygen saturation. PMID- 22316257 TI - In vitro evaluation of the efficacy of a veterinary dry heat fluid warmer. AB - OBJECTIVES: To evaluate the efficacy of a veterinary dry heat fluid warmer on ambient and prewarmed crystalloid fluids and refrigerated packed red blood cells (pRBC). DESIGN: Prospective in vitro study. SETTING: University teaching hospital. ANIMALS: None. INTERVENTIONS: Ambient and prewarmed crystalloid fluids and refrigerated pRBC were delivered via a standard fluid administration set at various rates. A thermistor continuously monitored fluid outflow temperature with and without a dry heat veterinary fluid warmer (study device). RESULTS: The outflow temperature was significantly higher with the study device as compared to control conditions for all fluids and rates tested. The maximum outflow temperature of approximately 35 degrees C (95 degrees F) occurred when the study device was applied to either ambient or prewarmed crystalloid fluids at 50 mL/h. In the study device trials, the outflow temperature of ambient crystalloid fluids ranged from 35.1 degrees to 27.3 degrees C (95.2 degrees to 81.1 degrees F) as the fluid rate increased from 50 to 999 mL/h. Control trials of prewarmed crystalloids produced outflow temperatures that rapidly approached ambient temperature. Addition of the study device to prewarmed crystalloids resulted in outflow temperatures that were similar to that of the corresponding ambient crystalloid trials. Control trials of refrigerated pRBC achieved ambient temperature at rates from 10 to 500 mL/h. With the study device, pRBC were maximally warmed to an outflow temperature of 35.8 degrees C (96.4 degrees F) at 100 mL/h. CONCLUSION: Although the study device generated statistically significant increases in outflow temperature of crystalloid fluids and pRBC, the ability of the device to decrease the metabolic cost of fluid administration is limited to specific clinical scenarios. The use of prewarmed crystalloid fluids with or without the study device offers minimal benefit over ambient temperature crystalloids. Substantial warming of pRBC occurs during administration, even without use of the study device. PMID- 22316258 TI - Characterization of acute kidney injury in hospitalized dogs and evaluation of a veterinary acute kidney injury staging system. AB - OBJECTIVE: To retrospectively apply standards characterizing acute kidney injury (AKI) used in human medicine to a population of critically ill hospitalized dogs in order to identify dogs with potential AKI based on subtle increases in plasma creatinine concentration. DESIGN: Retrospective study. SETTING: University Veterinary Medical Teaching Hospital. ANIMALS: One hundred and sixty-four client owned dogs admitted to the intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records of 164 dogs meeting the study inclusion criteria were reviewed to identify age, results of creatinine measurements, discharge status, length of stay, performance of general anesthesia, number of diagnoses, and calculated survival prediction index scores (SPI2). A veterinary AKI (VAKI) staging system was retrospectively applied to classify dogs based on increase in creatinine concentration from baseline as follows: stage 0 (S0; <150%), stage 1 (S1; 150-199% or >=26.5 MUmol/L [>=0.3 mg/dL]), stage 2 (S2; 200 299%), or stage 3 (S3; >=300%). Of the dogs evaluated, 140/164 were VAKI stage S0, 19/164 were classified as S1, 3/164 as S2, and 2/164 were S3. Mortality rate was greater for S1-3 (13/24; 54.2%) compared to S0 dogs (22/140; 15.7%) (P < 0.0001). Length of stay, general anesthesia, and number of diagnoses were not associated with survival. In a logistic regression model, stage and age were jointly, significantly associated with mortality (P = 0.0002 and P = 0.0330, respectively). Mean SPI2 scores were not different between S0 (0.52) and S1 (0.59) dogs (P = 0.23). Only 4/19 (21%) of S1 dogs had a peak plasma creatinine concentration above the laboratory reference interval. CONCLUSIONS: Dogs meeting VAKI stage 1-3 criteria were less likely to survive to discharge. Small increases in plasma creatinine concentration may be clinically relevant even when absolute values are within reference intervals. PMID- 22316259 TI - Sleep aid toxicosis in dogs: 317 cases (2004-2010). AB - OBJECTIVE: To summarize the signalment, clinical signs observed, time to onset of clinical signs, duration of clinical signs, and the outcome in a large case series of nonbenzodiazepine sleep aid ingestions in dogs, including 2 sleep aids that have not been previously described in the veterinary literature. DESIGN: Retrospective study conducted between 2004 and 2010. SETTING: An animal poison control center based out of Bloomington, MN. ANIMALS: During this time frame, 453 cases were identified involving 467 dogs. Of these cases, 150 cases were excluded due to incomplete medical records, multipet households, or the inability to calculate a dose exposure. A total of 317 dogs with presumed sleep aid medication toxicosis were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Records of dogs with sleep aid medication toxicosis identified by a review of an animal poison control center electronic database were evaluated. The most common sleep aid medications ingested were zolpidem (240/317 [75.7%]), eszopiclone (62/317 [19.5%]), and zaleplon (15/317 [4.7%]). Overall, clinical signs developed in 36% of patients (115/317), while 64% (202/317) remained asymptomatic. The most common organ systems affected and clinical signs seen involved the central nervous system (eg, agitation, sedation) and gastrointestinal tract (eg, anorexia, hypersalivation, vomiting). CONCLUSIONS: Overall, the prognosis for dogs with sleep aid medication toxicosis was excellent, and no fatalities were reported in this clinical population. As significant clinical signs can still be seen with ingestion, appropriate decontamination is warranted in asymptomatic patients via emesis or gastric lavage, followed by activated charcoal administration. Symptomatic patients should be hospitalized for monitoring and supportive care for a minimum of 12 hours or until clinical signs resolve. PMID- 22316260 TI - Intravenous fat emulsion as treatment for ivermectin toxicosis in three dogs homozygous for the ABCB1-1Delta gene mutation. AB - OBJECTIVE: To describe the outcome of 3 cases of ivermectin toxicosis in dogs homozygous for the ABCB1-1Delta gene mutation treated with intravenous fat emulsion (IFE). SERIES SUMMARY: One Australian Shepherd and 2 Miniature Australian Shepherds were treated for naturally occurring ivermectin toxicosis with IFE. All 3 dogs were homozygous for the ABCB1-1Delta gene mutation. Serum ivermectin concentrations confirmed ivermectin exposure in each case. All 3 dogs exhibited tremors, ptyalism, and central nervous system depression, which progressed over several hours to stupor in 2 dogs, and to a comatose state requiring mechanical ventilation in the remaining dog. A 20% formulation of IFE(a) was administered as an IV bolus (1.5 mL/kg) followed by a slow IV infusion (7.5-15 mL/kg [0.25-0.5 mL/kg/m], over 30 minutes). No change was observed in the neurologic status of any patient. Lipemia visible upon blood sampling persisted for 36 hours in 1 dog however, no other adverse effects were noted. Flumazenil (0.01 mg/kg IV), followed by a constant rate infusion(CRI) of 0.01 mg/kg/h IV was administered in 1 case, without any apparent clinical benefit or adverse effect. NEW OR UNIQUE INFORMATION PROVIDED: IFE was ineffective in the treatment of ivermectin toxicosis in these ABCB1-1Delta homozygous mutant dogs. Further investigation is necessary to determine why IFE treatment was unsuccessful in these cases and whether its use can be optimized to yield better results. PMID- 22316261 TI - Acute hyperammonemia after L-asparaginase administration in a dog. AB - OBJECTIVE: To describe a previously unreported and potentially fatal complication of L-asparaginase (L-asp) administration in a dog. CASE SUMMARY: A 7-year-old, 6.6 kg, female spayed Beagle presented with a 1-week history of progressive inappetance and lethargy. Diagnostic tests identified the presence of stage Vb lymphoma and liver dysfunction. The dog was treated with L-asp at 400 IU/kg, corticosteroids, and IV fluids. Within 12 hours the dog became depressed, vomited, and developed abdominal pain. Within 24 hours, the dog's mentation progressed from obtunded to comatose; subsequently the dog developed a "decerebrate posture." Blood ammonia concentrations exceeded 1,000 MUmol/L (1,700 MUg/dL). Treatment with broad-spectrum antimicrobials, lactulose enemas, and continuous renal replacement therapy were initiated without response and the dog suffered cardiopulmonary arrest. NEW OR UNIQUE INFORMATION PROVIDED: The purpose of this report is to describe the development of severe hyperammonemia after L asp therapy in a dog, which has not been previously reported in the literature. Given the rapid progression and fatal outcome observed in this case, early recognition may be crucial for management and treatment of this complication. PMID- 22316262 TI - Propylene glycol intoxication in a dog. AB - OBJECTIVE: To describe the clinical course, treatment, and outcome of a dog with propylene glycol intoxication. CASE SUMMARY: An adult castrated male Australian cattle dog presented to an emergency clinic for an acute onset of ataxia and disorientation after roaming a construction site unsupervised. He tested positive for ethylene glycol using a point-of-care test kit. Treatment for ethylene glycol intoxication included intermittent intravenous boluses of 20% ethanol and hemodialysis. Predialysis and postdialysis blood samples were submitted to the toxicology lab to assess for both ethylene and propylene glycol. The patient tested negative for ethylene glycol and positive for propylene glycol at 1100 mg/dL predialysis and 23 mg/dL postdialysis. The dog made a full recovery. NEW OR UNIQUE INFORMATION PROVIDED: To the authors' knowledge, this is the first report of documented propylene glycol intoxication in a dog, as well as the first report to describe hemodialysis as treatment for propylene glycol intoxication in a dog. PMID- 22316263 TI - Diagnostic challenges and treatment options of a suspected pericardial metallic projectile foreign body in a dog. AB - OBJECTIVE: To describe a case of a suspected pericardial metallic projectile foreign body in a dog with a history of trauma to the left shoulder and to review the literature regarding the management of cardiac and intracardiac foreign bodies. CASE SUMMARY: A 3-year-old male, neutered Brittany spaniel presented with a 10-day history of decreased activity and partial anorexia. Serial thoracic radiographs identified a migrating pericardial metallic projectile foreign body and an echocardiogram diagnosed pericardial effusion and abdominal ultrasound identified the presence of ascites. Concern for a possible effusive-constrictive pericarditis prompted a subphrenic pericardectomy performed via thoracoscopy. The foreign body was not recovered. Six months postsurgery, the dog remained asymptomatic. NEW OR UNIQUE INFORMATION PROVIDED: Considering the high rate of complications that develop in human patients where the foreign bodies are not removed, veterinarians should be aware of risks associated with long standing pericardial foreign bodies even when no clinical signs are present. Guidelines from the human literature may be considered for investigation of, and treatment options for, cardiac and intracardiac metallic projectile foreign bodies in dogs. PMID- 22316266 TI - Prevalence of inflammatory markers (high-sensitivity C-reactive protein, nuclear factor-kappaB, and adiponectin) in Indian patients with type 2 diabetes mellitus with and without macrovascular complications. AB - BACKGROUND: Atherosclerosis is more prevalent in subjects with diabetes mellitus. Recent evidence suggests that diabetic atherosclerosis is not simply a disease of hyperlipidemia, but is also an inflammatory disorder. Our aim was to study the prevalence of inflammatory markers such as high-sensitivity C-reactive protein (hsCRP), adiponectin, and nuclear factor-kappaB (NF-kappaB) expression, in peripheral blood mononuclear cells in Indian patients with type 2 diabetes mellitus (T2DM) with and without macrovascular disease (MVD). METHODS: A total of 29 consecutive cases of T2DM with proven MVD (group A), 28 matched cases without MVD (group B), and 14 healthy controls (group C) were evaluated for the clinical parameters fasting blood glucose (FBG), 2-h postprandial blood glucose (PPBG), glycosylated hemoglobin (HbA1c), lipid profile, and the above-mentioned inflammatory markers. RESULTS: Diabetic subjects with T2DM had higher hsCRP and NF-kappaB expression and lower values of adiponectin compared to healthy controls. Group A had significantly higher serum hsCRP than group B (P=0.0001) despite comparable values of BMI, FBG, 2-h PPBG, HbA1c, and lipid parameters. Group A had significantly higher serum hsCRP and NF-kappaB expression and significantly lower levels of adiponectin than group C (P=0.0001, 0.007, and 0.02, respectively). In Group A, serum adiponectin negatively correlated with NF kappaB expression. In Group B, adiponectin values correlated negatively with both FBG and 2-h PPBG. CONCLUSIONS: Indian subjects with T2DM with or without MVD had higher hsCRP and lower adiponectin values as compared to healthy controls, whereas hsCRP was significantly higher in those with MVD, suggesting that our patients with T2DM were in a proinflammatory state. PMID- 22316267 TI - Recycling of porcelain tile polishing residue in portland cement: hydration efficiency. AB - Ceramic tiles are widely used by the construction industry, and the manufacturing process of ceramic tiles generates as a major residue mud derived from the polishing step. This residue is too impure to be reused in the ceramic process and is usually discarded as waste in landfills. But the analysis of the particle size and concentration of silica of this residue shows a potential use in the manufacture of building materials based on portland cement. Tests were conducted on cement pastes and mortars using the addition of 10% and 20% (mass) of the residue. The results of compressive strength in mortars made up to 56 days showed a significant increase in compressive strength greater than 50%. The result of thermogravimetry shows that portlandite is consumed by the cement formed by the silica present in the residue in order to form calcium silicate hydrate and featuring a pozzolanic reaction. This effect improves the performance of cement, contributes to research and application of supplementary cementitious materials, and optimizes the use of portland cement, reducing the environmental impacts of carbon dioxide emissions from its production. PMID- 22316268 TI - Use of antimicrobial agents in food processing systems. AB - This article reviews the patents showing the use of antimicrobial agents in processing plants to eliminate the growth of the microorganism that affects on the quality and safety of the end products. Several materials have unique antimicrobial effects, especially towards biofilms in the processing equipments. The selection of a proper antimicrobial agent is essential to obtain the best results in preserving foods. The antimicrobial agent must not be toxic, and many factors need to be considered in choosing the right antimicrobial agent. PMID- 22316269 TI - Nanotechnology and its impact on food and nutrition: a review. AB - The last decade has witnessed the development and arrival of novel nano-based food materials, innovative food packaging, intelligent delivery mechanisms of nutrients and bioactive materials, implementation of green nanotechnologies for crop production and nano-biosensors to provide safer foods and waste reduction. Opportunities to exploit and develop nanotechnologies in the food sector have resulted in a large number of patents as food technologists and engineers continue to identify novel ways to re-invent food products that would appeal to consumers on a global scale. However, in the pursuit of delivering patentable technologies, concerns over consumer health and safety in the use of nanoparticles in foods is an ongoing challenge. This review aims to present a discussion of the recent innovations of nano-based food technologies in terms of patented knowledge across a number of applications, future trends and impact on the food industry. As food regulators respond to the potential threat of nanomaterials guided by toxicity studies, we also discuss recent developments and initiatives being adopted to ensure the safe use of nanomaterials based on current predictions. PMID- 22316270 TI - Strategies for salt reduction in foods. AB - The amounts of sodium chloride in the formulation of a variety of foods like bakery, meats and dairy foods, ready meals, sauces and snacks, are relatively large and thus, have a strong contribution on the salt dietary intake. There is a clear demand by the consumers and medical associations to reduce the salt content in foods. Different strategies have been proposed and most of them consist of the replacement of sodium chloride by other salts and the addition of other substances for an acceptable sensory quality. The recent patents for salt reduction and their applications in foods are reviewed in this manuscript. PMID- 22316271 TI - Use of grape polyphenols for promoting human health: a review of patents. AB - We presently discuss the use of grape polyphenols for promoting human health and disclose recent patents on the subject. The biological effects of grape polyphenols in human and experimental models demonstrate antioxidant properties closely associated with the maintenance of endothelial function, increase in antioxidant capacity, protection against LDL oxidation and neuroprotective effects. Recent patents regarding grape polyphenols show a tendency to return to natural products with a minimum use of severe extraction processes and organic solvents. Moreover, the recent patents regarding human health show more pharmaceutical use of grape juice and other polyphenol-rich products. The application of such products in clinical trials as a substitute or co-adjuvant with drugs may be useful in future research. PMID- 22316272 TI - Cereal bran fractionation: processing techniques for the recovery of functional components and their applications to the food industry. AB - Bran is the outer part of cereal grains that is separated during the cereals de hulling and milling processes. It was considered in the past a by-product of cereal industry employed mainly as animal feed. Cereal bran, being particularly rich in different functional biopolymers, bio-active compounds and essential fatty acids, attracted the interest of pharmaceutical and food industry. Furthermore, the peculiar techno-functional properties of brans together with their particular physiological and nutritional aspects have led to a great interest in their incorporation as main or secondary components in different groups of food products including bakery and confectionery products, breakfast cereals and extruded foodstuffs, emulsions and functional dairy products and pasta products. In the first part of the present work the main fractionation processes, bran fractions properties and their physicochemical and technological properties are briefly reviewed. In the second part, relevant applications, with emphasis on patents, in food industry are reviewed as well. PMID- 22316273 TI - High IFN-gamma and TNF production by peripheral NK cells of Colombian patients with different clinical presentation of Plasmodium falciparum. AB - BACKGROUND: In Colombia, Plasmodium falciparum infection rarely results in severe disease or mortality compared to infections in African populations. During natural infection NK cells exhibit a cytolytic effect and regulate dendritic cells, macrophages, neutrophils as well as affect antigen specific T and B cell responses. To characterize the NK cells in P. falciparum infected patients of a highly endemic region of Colombia, the degree of NK proliferation and production of IFN gamma and TNF production in these cells were explored. METHODS: Seventeen patients with acute and three with severe P. falciparum malaria patients from the Northwest region of the country were recruited in the study. In addition, 20 healthy controls were included: 10 from Medellin (no-transmission area) and 10 from the Uraba region (a malaria endemic area). Immunophenotypic analysis of peripheral mononuclear cells was performed by FACS to detect total number of NK cells, subtypes and intracellular IFNgamma and TNF production by NK cells in the different patient groups. RESULTS: The total mean CD56(+)/CD3(-) NK cell proportions in acute and severe malaria subjects were 9.14% (7.15%CD56(dim), 2.01%CD56(bright)) and 19.62% (16.05%CD56(dim), 3.58%CD56(bright)), respectively, in contrast to healthy controls from endemic (total mean CD56(+)/CD3(-)1.2%) and non-endemic area (total mean CD56(+)/CD3(-) 0.67%). Analysis of basal IFNgamma and TNF levels confirmed the CD56(bright) NK population as the main cytokine producer (p < 0.0001) in the groups affected with malaria, with the CD56(dim) NK cell exhibiting the highest potential of TNF production after stimulus in the acute malaria group. CONCLUSIONS: The results confirm the important role of not only CD56(bright) but also of CD56(dim) NK cell populations as producers of the two cytokines in malaria patients in Colombia. PMID- 22316274 TI - High preoperative plasma neopterin predicts delirium after cardiac surgery in older adults. AB - OBJECTIVES: To examine the association between plasma levels of pterins and amino acids and postoperative delirium. DESIGN: Prospective cohort study. SETTING: Cardiothoracic service in an university hospital in Rotterdam, the Netherlands. PARTICIPANTS: One hundred twenty-five individuals aged 70 and older undergoing elective cardiac surgery. MEASUREMENTS: Plasma pterins and amino acids were measured pre- and postoperatively. Using multiple logistic regression analyses, the associations between pterins and amino acid levels and postoperative delirium were examined in relation to age, sex, comorbidity, cognitive functioning (Mini Mental State Examination (MMSE) score), and cardiac risk factors. RESULTS: Delirium incidence in the main study group was 31.3%. The preoperative measures associated with delirium were neopterin (odds ratio (OR) = 1.05, P = .009); MMSE score less than 28 (OR = 4.39, P = .001); European System for Cardiac Operative Risk Evaluation score greater than 6 (OR = 2.84, P = .03); and combined coronary artery bypass graft (CABG) and aortic, mitral, or tricuspid valve surgery (OR = 4.32, P = .01). Postoperative measures associated with delirium were neopterin (OR = 3.84, P = .02), homovanillic acid (HVA, OR = 1.01, P = .04), and preoperative MMSE score less than 28 (OR = 3.32, P = .008). CONCLUSION: Preoperatively high neopterin levels predicted delirium after cardiac surgery in older adults, in addition to the well-known risk factors of poor cognitive function, high cardio-surgical risk, and combined CABG and valve surgery. Postoperative neopterin and HVA levels were also found to be associated with delirium, together with preoperative cognitive functioning. Plasma neopterin may be a candidate biomarker for delirium after cardiac surgery in these older adults. PMID- 22316275 TI - Cost-effectiveness of zoledronic acid vs clodronic acid for newly-diagnosed multiple myeloma from the United Kingdom healthcare system perspective. AB - OBJECTIVE: In the Medical Research Council Myeloma IX Study (MMIX), zoledronic acid (ZOL) 4 mg 3-4/week reduced the incidence of skeletal-related events (SREs), increased progression free survival (PFS), and prolonged overall survival (OS), compared with clodronic acid (CLO) 1600 mg daily, in 1970 patients with newly diagnosed multiple myeloma (MM). METHODS: An economic model was used to project PFS, OS, the incidence of SREs and adverse events and expected lifetime healthcare costs for patients with newly-diagnosed MM who are alternatively assumed to receive ZOL or CLO. The incremental cost-effectiveness ratio [ICER] of ZOL vs CLO was calculated as the ratio of the difference in cost to the difference in quality-adjusted life years (QALYs). Model inputs were based on results of MMIX and published sources. RESULTS: Compared with CLO, treatment with ZOL increases QALYs by 0.30 at an additional cost of L1653, yielding an ICER of L5443 per QALY gained. If the threshold ICER is L20,000 per QALY, the estimated probability that ZOL is cost-effective is 90%. LIMITATIONS: The main limitation of this study is the lack of data on the effects of zoledronic acid on survival beyond the end of follow-up in the MMIX trial. However, cost-effectiveness was favourable even under the highly conservative scenario in which the timeframe of the model was limited to 5 years. CONCLUSIONS: Compared with clodronic acid, zoledronic acid represents a cost-effective treatment alternative in patients with multiple myeloma. PMID- 22316276 TI - Serum brain natriuretic peptide and C-reactive protein levels in adolescent with polycystic ovary syndrome. AB - OBJECTIVE: Our primary aim was to investigate whether N-terminal pro-brain natriuretic peptide (NT-proBNP) increases in adolescent with polycystic ovary syndrome (PCOS) compared with healthy controls and secondary aim was to determine whether metabolic and hormonal differences exist between groups. METHODS: In this cross-sectional study, 25 adolescent patients with PCOS and 25 normal ovulatory control not suffering from PCOS were involved in the study. Fasting serum NT proBNP, C-reactive protein (CRP), homocystein, insulin levels and biochemical and hormonal parameters were measured. RESULTS: Serum NT-proBNP was not significantly different in PCOS subjects (0.62 +/- 0.80 vs 1.12 +/- 1.51 ng/mL, p = 0.154). The mean serum fasting insulin levels (22.64 +/- 10.51 vs 13.32 +/- 3.97 mIU/mL, p = 0.001) and Homeostasis Model Assessment Insulin-Resistance Index (HOMA-IR) levels (5.16 +/- 1.81 vs 2.97 +/- 0.89, p = 0.001) were significantly high in the study group. The median serum CRP levels were not significantly different between groups (1 [1-12] vs 1 [1-19] g/dL, p = 0.286). CONCLUSIONS: The present study demonstrated that the levels of BNP, CRP and homocystein were not different in PCOS subjects. Serum insulin levels and HOMA-IR were significantly higher in PCOS subjects. Possible serum markers for PCOS-related metabolic abnormalities and cardiovascular events, may not present in the adolescent years. PMID- 22316277 TI - Adhesion of microchannel-based complementary surfaces. AB - We show that highly enhanced and selective adhesion can be achieved between surfaces patterned with complementary microchannel structures. An elastic material, poly(dimethylsiloxane) (PDMS), was used to fabricate such surfaces by molding into a silicon master with microchannel profiles patterned by photolithography. We carried out adhesion tests on both complementary and mismatched microchannel/micropillar surfaces. Adhesion, as measured by the energy release rate required to propagate an interfacial crack, can be enhanced by up to 40 times by complementary interfaces, compared to a flat control, and slightly enhanced for some special noncomplementary samples, despite the nearly negligible adhesion for other mismatched surfaces. For each complementary surface, we observe defects in the form of visible striations, where pillars fail to insert fully into the channels. The adhesion between complementary microchannel surfaces is enhanced by a combination of a crack-trapping mechanism and friction between a pillar and channel and is attenuated by the presence of defects. PMID- 22316278 TI - On the intercalation of the iodine-iodide couple on layered double hydroxides with different particle sizes. AB - Molecular iodine was intercalated from nonaqueous solution into microsized ZnAl layered double hydroxide (LDH) in the iodide form, generating the I(3)(-)/I(-) redox couple into the interlayer region. Chloroform, ethanol, acetonitrile, or diethyl ether were used as solvents to dissolve the molecular iodine. The intercalation compounds were characterized by thermogravimetric analysis, X-ray powder diffraction, UV-vis spectroscopy, and scanning and transmission electron microscopy. The stability of iodine-solvent adducts and the iodine concentration affected the LDH iodine loading, and samples with I(2)/I(-) molar ratio ranging from 0.14 to 0.82 were prepared. Nanosized, well dispersible LDH, synthesized by the urea method in water-ethylene glycol media, were also prepared and successfully functionalized with the I(3)(-)/I(-) redox couple applying the conditions optimized for the micrometric systems. PMID- 22316279 TI - Highly selective carbon dioxide uptake by [Cu(bpy-n)2(SiF6)] (bpy-1 = 4,4' bipyridine; bpy-2 = 1,2-bis(4-pyridyl)ethene). AB - A previously known class of porous coordination polymer (PCP) of formula [Cu(bpy n)(2)(SiF(6))] (bpy-1 = 4,4'-bipyridine; bpy-2 = 1,2-bis(4-pyridyl)ethene) has been studied to assess its selectivity toward CO(2), CH(4), N(2), and H(2)O. Gas sorption measurements reveal that [Cu(bpy-1)(2)(SiF(6))] exhibits the highest uptake for CO(2) yet seen at 298 K and 1 atm by a PCP that does not contain open metal sites. Significantly, [Cu(bpy-1)(2)(SiF(6))] does not exhibit particularly high uptake under the same conditions for CH(4), N(2), and, H(2)O, presumably because of its lack of open metal sites. Consequently, at 298 K and 1 atm [Cu(bpy 1)(2)(SiF(6))] exhibits a relative uptake of CO(2) over CH(4) of ca. 10.5:1, the highest value experimentally observed in a compound without open metal sites. [Cu(bpy-2)(2)(SiF(6))] exhibits larger pores and surface area than [Cu(bpy 1)(2)(SiF(6))] but retains a high CO(2)/CH(4) relative uptake of ca. 8:1. PMID- 22316280 TI - Allometric or lean body mass scaling of propofol pharmacokinetics: towards simplifying parameter sets for target-controlled infusions. AB - Uncertainty exists as to the most suitable pharmacokinetic parameter sets for propofol target-controlled infusions (TCI). The pharmacokinetic parameter sets currently employed are clearly not universally applicable, particularly when patient attributes differ from those of the subjects who participated in the original research from which the models were derived. Increasing evidence indicates that the pharmacokinetic parameters of propofol can be scaled allometrically as well as in direct proportion to lean body mass (LBM). Appraisal of hitherto published studies suggests that an allometrically scaled pharmacokinetic parameter set may be applicable to a wide range of patients ranging from children to obese adults. On the other hand, there is evidence that propofol pharmacokinetic parameters, scaled linearly to LBM, provide improved dosing in normal and obese adults. The 'Schnider' pharmacokinetic parameter set that has been programmed into commercially available TCI pumps cannot be employed at present for morbidly obese patients (body mass index >40 kg/m2), because of anomalous behaviour of the equation used to calculate LBM, resulting in administration of excessive amounts of propofol. Simulations of TCI using improved equations to calculate LBM indicate that the Schnider model delivers similar amounts of propofol to morbidly obese patients as do the allometrically scaled pharmacokinetic parameter sets. These hypotheses deserve further investigation. To facilitate further investigation, researchers are encouraged to make their data freely available to the WorldSIVA Open TCI Initiative (http://opentci.org). PMID- 22316282 TI - Factors associated with preventive dental care-seeking behavior among people living with HIV. AB - OBJECTIVES: This study examined factors associated with preventive dental care seeking behavior among HIV-positive adults who participated in a federally funded demonstration project to expand access to oral health care. METHODS: Two thousand one hundred eighty-seven adults living with human immunodeficiency virus (HIV) in the United States were enrolled in free dental care and were interviewed about their reasons for seeking care, their oral health, and overall health status. Multivariate analysis using Generalized Estimating Equations to control for clustering by site was conducted to identify factors associated with preventive care-seeking behavior. RESULTS: Forty-one percent of participants reported the only reason they sought dental care was for preventive care, to receive a checkup or cleaning. Factors associated with preventive care-seeking behavior in multivariate analysis included no unmet need for dental care since testing HIV positive, no dental insurance, taking HIV medications and better overall oral health. CONCLUSIONS: Many HIV-positive adults may seek preventive care when it is offered at no cost. Interventions that address unmet needs and target individuals who are not taking HIV medications or have poorer oral health may improve preventive practices. PMID- 22316281 TI - Stimulation of peripheral kappa opioid receptors inhibits inflammatory hyperalgesia via activation of the PI3Kgamma/AKT/nNOS/NO signaling pathway. AB - BACKGROUND: In addition to their central effects, opioids cause peripheral analgesia. There is evidence showing that peripheral activation of kappa opioid receptors (KORs) inhibits inflammatory pain. Moreover, peripheral MU-opioid receptor (MOR) activation are able to direct block PGE(2)-induced ongoing hyperalgesia However, this effect was not tested for KOR selective activation. In the present study, the effect of the peripheral activation of KORs on PGE(2) induced ongoing hyperalgesia was investigated. The mechanisms involved were also evaluated. RESULTS: Local (paw) administration of U50488 (a selective KOR agonist) directly blocked, PGE(2)-induced mechanical hyperalgesia in both rats and mice. This effect was reversed by treating animals with L-NMMA or N-propyl-L arginine (a selective inhibitor of neuronal nitric oxide synthase, nNOS), suggesting involvement of the nNOS/NO pathway. U50488 peripheral effect was also dependent on stimulation of PI3Kgamma/AKT because inhibitors of these kinases also reduced peripheral antinociception induced by U50488. Furthermore, U50488 lost its peripheral analgesic effect in PI3Kgamma null mice. Observations made in vivo were confirmed after incubation of dorsal root ganglion cultured neurons with U50488 produced an increase in the activation of AKT as evaluated by western blot analyses of its phosphorylated form. Finally, immunofluorescence of DRG neurons revealed that KOR-expressing neurons also express PI3Kgamma (? 43%). CONCLUSIONS: The present study indicates that activation of peripheral KORs directly blocks inflammatory hyperalgesia through stimulation of the nNOS/NO signaling pathway which is probably stimulated by PI3Kgamma/AKT signaling. This study extends a previously study of our group suggesting that PI3Kgamma/AKT/nNOS/NO is an important analgesic pathway in primary nociceptive neurons. PMID- 22316283 TI - Ultrasound guided ablative-laser assisted photodynamic therapy of basal cell carcinoma (US-aL-PDT). AB - OBJECTIVE: With proper noninvasive ultrasound measurement of tumor depth, case selection for laser pre-ablation followed by PDT is possible. This combination of methods provides a less invasive approach to the treatment of BCC. BACKGROUND DATA: Basal cell carcinoma (BCC) primarily affects the face, and, therefore, radical excision is problematic because of the possibility of poor aesthetic outcomes. Photodynamic therapy (PDT) offers an advantage in aesthetic outcomes, but topical PDT is only effective for tumors with a depth up to 2 mm. MATERIALS AND METHODS: Seventy-five histologically verified BCCs from 67 patients were selected and divided into three therapeutic groups based on the tumor depth, which was determined by 20 MHz skin ultrasound. The three groups were: A/<2 mm (PDT), B/ 2-3 mm (Er:YAG laser ablation+PDT), and C/>3 mm (diode laser ablation+PDT). The treatment consisted of laser ablation (or no ablation) followed by the application of methyl-aminolevulinate (MAL) and a 3-h treatment period using an occlusive bandage. Subsequently, illumination with 630 nm (MAL PDT) was performed. MAL-PDT was repeated 1-3 weeks after the first treatment. A clinical evaluation was performed after 6 months. RESULTS: A 100% clearance rate (CR) in the group with the deepest tumors was observed. In addition, a 94.7% CR occurred in the group with tumors 2-3 mm in depth, and an 81.2% CR was observed in the group with superficial tumors. CONCLUSIONS: With proper ultrasound case selection and laser ablation before MAL-PDT, the depth of a BCC lesion is not a limiting factor for PDT, and aesthetic outcomes are very good. Therefore, ultrasound-guided ablative laser-assisted PDT of BCC can be the method of choice, particularly in aesthetically challenging cases. PMID- 22316284 TI - Choice of diet impacts the incidence of stroke-related symptoms in the spontaneously hypertensive stroke-prone rat model. AB - The spontaneously hypertensive stroke-prone (SHRSP) rat is a commonly used model of cerebrovascular disease and hypertension. SHRSP rats have been shown to develop stroke-related symptoms (SRS) by age 14 weeks when fed a purified diet, such as AIN-93G, supplemented with 1% NaCl. We conducted a pathology pilot study to compare the incidence of SRS in SHRSP rats fed either AIN-93G (with 1% NaCl in drinking water) or commercially available rat chow (with 4% NaCl in the diet), starting at 8 weeks of age. These results prompted us to analyze data from 5 earlier feeding trials using SHRSP rats. Overall, we found that SHRSP rats fed AIN-93G purified diet for 8 or 17 weeks did not demonstrate SRS (n = 18), whereas all SHRSP rats fed lab chow exhibited SRS at age 15.1 +/- 0.6 weeks (n = 23). In addition, SHRSP rats fed lab chow had decreased mass gain starting at age 13 weeks, as well as decreased feed efficiencies after the first 5 weeks of feeding (p < 0.05). In conclusion, our data suggest that diet composition is a major contributor to the onset of stroke in SHRSP rats and that diet choice should be critically evaluated based on endpoint measures in the SHRSP model. PMID- 22316285 TI - Palladium(II)-catalyzed enantioselective synthesis of 2-vinyl oxygen heterocycles. AB - 2-Vinylchromanes (1), 2-vinyl-1,4-benzodioxanes (2), and 2,3-dihydro-2-vinyl-2H 1,4-benzoxazines (3) can be prepared in high yields (90-98%) and excellent enantiomeric purities (87-98% ee) by [COP-OAc](2)-catalyzed cyclization of phenolic (E)-allylic trichloroacetimidate precursors. Deuterium-labeling and computational experiments are consistent with these cyclization reactions taking place by an anti-oxypalladation/syn-deoxypalladation mechanism. 2-Vinylchromanes can also be prepared in good yields and high enantiomeric purities from analogous (E)-allylic acetate precursors, which constitutes the first report that acetate is a competent leaving group in COP-catalyzed enantioselective S(N)2' substitution reactions. PMID- 22316286 TI - Multilayered carbon nanotube/polymer composite based thermoelectric fabrics. AB - Thermoelectrics are materials capable of the solid-state conversion between thermal and electrical energy. Carbon nanotube/polymer composite thin films are known to exhibit thermoelectric effects, however, have a low figure of merit (ZT) of 0.02. In this work, we demonstrate individual composite films of multiwalled carbon nanotubes (MWNT)/polyvinylidene fluoride (PVDF) that are layered into multiple element modules that resemble a felt fabric. The thermoelectric voltage generated by these fabrics is the sum of contributions from each layer, resulting in increased power output. Since these fabrics have the potential to be cheaper, lighter, and more easily processed than the commonly used thermoelectric bismuth telluride, the overall performance of the fabric shows promise as a realistic alternative in a number of applications such as portable lightweight electronics. PMID- 22316287 TI - Does the radiologic technologist or the fluoroscopy time affect treatment success with shockwave lithotripsy? AB - BACKGROUND AND PURPOSE: The minimally invasive nature and effectiveness of shockwave lithotripsy (SWL) has made it one of the primary treatment modalities for urinary tract calculi. Several factors determining the success of SWL treatment have been studied, including stone factors (ie, location, size, and composition) and patient factors (ie, patient habitus and skin-to-stone distance). Our objective was to determine if either the assisting radiologic technologist or the amount of fluoroscopy time used has an impact on SWL success. PATIENTS AND METHODS: We compared the outcome of 536 SWL treatments across three radiologic technologists. We also evaluated the average amount of fluoroscopy time used in treatment success vs failures in this same cohort. The outcomes measured were stone-free and successful fragmentation rate at 2 weeks and 3 months. Successful fragmentation was defined as being either stone free, having residual sand, or with an asymptomatic fragment <= 4 mm on radiography of the kidneys, ureters, and bladder. RESULTS: The patients treated by the three different radiologic technologists were comparable with respect to body mass index, stone side and location, presence of ureteral stent, and mean stone area (mm(2)). The stone-free and successful fragmentation rates at 2 weeks and 3 months between the three radiologic technologists were not significantly different. When examining fluoroscopy time, we found a significantly greater mean fluoroscopy time was used in treatments with successful fragmentation at 2 weeks (3.16 min vs 2.72 min, P=0.0001) and 3 months (3.12 min vs 2.75 min, P=0.0015) compared with treatment failures. CONCLUSION: The radiologic technologist did not have a significant impact on SWL treatment outcome at 2 weeks and 3 months. Successful SWL fragmentation at 2 weeks and 3 months, however, was associated with a greater amount of fluoroscopy time, suggesting that using fluoroscopy to ensure accurate targeting during SWL is important for successful fragmentation. PMID- 22316288 TI - West Nile virus vector Culex modestus established in southern England. AB - BACKGROUND: The risk posed to the United Kingdom by West Nile virus (WNV) has previously been considered low, due to the absence or scarcity of the main Culex sp. bridge vectors. The mosquito Culex modestus is widespread in southern Europe, where it acts as the principle bridge vector of WNV. This species was not previously thought to be present in the United Kingdom. FINDINGS: Mosquito larval surveys carried out in 2010 identified substantial populations of Cx. modestus at two sites in marshland in southeast England. Host-seeking-adult traps placed at a third site indicate that the relative seasonal abundance of Cx. modestus peaks in early August. DNA barcoding of these specimens from the United Kingdom and material from southern France confirmed the morphological identification. CONCLUSIONS: Cx. modestus appears to be established in the North Kent Marshes, possibly as the result of a recent introduction. The addition of this species to the United Kingdom's mosquito fauna may increase the risk posed to the United Kingdom by WNV. PMID- 22316289 TI - Novel insights in the role of peripheral corticotropin-releasing factor and mast cells in stress-induced visceral hypersensitivity. AB - Visceral hypersensitivity is one of the hallmarks in irritable bowel syndrome (IBS) pathophysiology. Stress is well known to affect visceral sensitivity in humans and rodents, an effect which is associated in part with alterations of intestinal epithelial permeability in rodents. Although the pathophysiology of visceral hypersensitivity is still unclear, two key factors have been identified as playing a major role in its modulation, namely peripheral corticotropin releasing factor (CRF) and mast cells. In a recent study in Neurogastroenterology and Motility, van den Wijngaard et al. demonstrate that the mast-cell dependent visceral hypersensitivity observed in maternally separated rats after an acute exposure to a psychological stress can be prevented but not reversed by the peripherally restricted CRF receptor antagonist, alpha-helical CRF(9-41). They further show that the preventive effect of the CRF receptor antagonist is linked to a stabilization of mast cells and maintenance of the epithelial barrier at the colonic level. These data suggest that post stress mast cell activation and subsequent visceral hypersensitivity are not targeted by peripheral CRF receptor antagonists. These novel insights in the role of peripheral CRF in the modulation of stress-induced visceral hypersensitivity add to our growing understanding of the mechanisms that may lie at the origin of visceral pain disturbances following stress and will contribute to enhance the development of drugs that may have potential therapeutic benefits for IBS patients. PMID- 22316290 TI - Effects of effortful swallow on esophageal function in healthy adults. AB - BACKGROUND: Treatment for esophageal dysmotility is currently limited to primarily pharmacologic intervention, which has questionable utility and frequently associated negative side effects. A potential behavioral intervention for esophageal dysmotility is the effortful oropharyngeal swallow. A previous pilot study using water perfusion manometry found an increase in distal esophageal amplitudes during effortful vs non-effortful swallowing. The current study sought to duplicate the previous study with improvements in methodology. METHODS: The effects of swallow condition (effortful vs non-effortful), sensor site, and gender on esophageal amplitude, duration, velocity, and bolus clearance were examined for 18 adults (nine males and nine females, mean age = 29.9 years) via combined solid-state manometry and intraluminal impedance. KEY RESULTS: The effortful swallow condition yielded significantly higher esophageal amplitudes across all sensor locations (P < 0.05). Further, the effortful swallowing decreased the risk of incomplete bolus clearance when compared with non-effortful swallowing (OR: 0.51; 95% CI: 0.30-0.86). CONCLUSIONS & INFERENCES: With improved manometric instrumentation, larger participant numbers, and methodology that controlled for potential confounding factors, this study confirms and advances the results of the previous pilot study: Volitional manipulation of the oropharyngeal phase of swallowing using the effortful swallow indeed affects esophageal physiology. Thus, the effortful swallow offers a behavioral manipulation of the esophageal phase of swallowing, and future studies will determine its clinical potential for treating esophageal dysmotility in patient populations. PMID- 22316291 TI - Smooth muscle caldesmon modulates peristalsis in the wild type and non-innervated zebrafish intestine. AB - BACKGROUND: The high molecular weight isoform of the actin-binding protein Caldesmon (h-CaD) regulates smooth muscle contractile function by modulating cross-bridge cycling of myosin heads. The normal inhibitory activity of h-CaD is regulated by the enteric nervous system; however, the role of h-CaD during intestinal peristalsis has never been studied. METHODS: We identified a zebrafish paralog of the human CALD1 gene that encodes an h-CaD isoform expressed in intestinal smooth muscle. We examined the role of h-CaD during intestinal peristalsis in zebrafish larvae by knocking down the h-CaD protein using an antisense morpholino oligonucleotide. We also developed transgenic zebrafish that express inhibitory peptides derived from the h-CaD myosin and actin-binding domains, and examined their effect on peristalsis in wild-type zebrafish larvae and sox10 (colourless) mutant larvae that lack enteric nerves. KEY RESULTS: Genomic analyses identified two zebrafish Caldesmon paralogs. The cald1a ortholog encoded a high molecular weight isoform generated by alternative splicing whose intestinal expression was restricted to smooth muscle. Propulsive intestinal peristalsis was increased in wild-type zebrafish larvae by h-CaD knockdown and by expression of transgenes encoding inhibitory myosin and actin-binding domain peptides. Peristalsis in the non-innervated intestine of sox10 (colourless) larvae was partially restored by h-CaD knockdown and expression of the myosin binding peptide. CONCLUSIONS & INFERENCES: Disruption of the normal inhibitory function of h-CaD enhances intestinal peristalsis in both wild-type zebrafish larvae and mutant larvae that lack enteric nerves, thus confirming a physiologic role for regulation of smooth muscle contraction at the actin filament. PMID- 22316293 TI - Patient enablement requires physician empathy: a cross-sectional study of general practice consultations in areas of high and low socioeconomic deprivation in Scotland. AB - BACKGROUND: Patient 'enablement' is a term closely aligned with 'empowerment' and its measurement in a general practice consultation has been operationalised in the widely used patient enablement instrument (PEI), a patient-rated measure of consultation outcome. However, there is limited knowledge regarding the factors that influence enablement, particularly the effect of socio-economic deprivation. The aim of the study is to assess the factors influencing patient enablement in GP consultations in areas of high and low deprivation. METHODS: A questionnaire study was carried out on 3,044 patients attending 26 GPs (16 in areas of high socio-economic deprivation and 10 in low deprivation areas, in the west of Scotland). Patient expectation (confidence that the doctor would be able to help) was recorded prior to the consultation. PEI, GP empathy (measured by the CARE Measure), and a range of other measures and variables were recorded after the consultation. Data analysis employed multi-level modelling and multivariate analyses with the PEI as the dependant variable. RESULTS: Although numerous variables showed a univariate association with patient enablement, only four factors were independently predictive after multilevel multivariate analysis; patients with multimorbidity of 3 or more long-term conditions (reflecting poor chronic general health), and those consulting about a long-standing problem had reduced enablement scores in both affluent and deprived areas. In deprived areas, emotional distress (GHQ-caseness) had an additional negative effect on enablement. Perceived GP empathy had a positive effect on enablement in both affluent and deprived areas. Maximal patient enablement was never found with low empathy. CONCLUSIONS: Although other factors influence patient enablement, the patients' perceptions of the doctors' empathy is of key importance in patient enablement in general practice consultations in both high and low deprivation settings. PMID- 22316294 TI - Laparoscopic-assisted cystotomy and cystostomy for treatment of cystic calculus in a gelding. AB - OBJECTIVE: To report laparoscopic-assisted cystotomy and inguinal cystostomy for treating bladder urolithiasis in a gelding. STUDY DESIGN: Clinical report. ANIMALS: Twelve-year-old Appaloosa gelding. METHODS: A laparoscopic approach was used to locate and grasp the bladder, which was exteriorized through an enlarged instrument portal for cystotomy to remove the calculus. During withdrawal, the calculus fragmented into multiple pieces. To avoid urethral occlusion and facilitate elimination of these fragments, an inguinal cystostomy was created. The seromuscular layer of the bladder was circumferentially secured to the abdominal fascia and bladder mucosa margins were sutured to the skin. RESULTS: At 2-year follow-up, the gelding was in good condition with mild urine scald of the left ventral abdomen. CONCLUSION: Laparoscopic-assisted cystotomy was used for calculus removal and inguinal cystostomy for successful fragment elimination. PMID- 22316295 TI - Antioxidant, antiproliferative, and pro-apoptotic activities of a saponin extract derived from the roots of Panax notoginseng (Burk.) F.H. Chen. AB - Dietary and medicinal uses of Panax notoginseng have been associated with reduced risk of cancer. This study was designed to investigate the profiles of P. notoginseng saponin extract (PNSE), the major bioactive ingredients in P. notoginseng (Burk.) F.H. Chen, by high-performance liquid chromatography, and, for the first time, the anticancer effect of PNSE in the human colon cancer cell line LoVo was further evaluated. The major saponins present in PNSE were ginsenosides Rg1 (31.1%) and Rb1 (34.4%), and the total content of the eight saponins identified (notoginsenoside R1, ginsenosides Rg1, Re, Rb1, Rc, and Rd, and isomeric ginsenosides Rb2 and Rb3) was 81.7%, indicating that it was a highly purified standardized saponin extract. Furthermore, PNSE was found to have a markedly cytotoxic effect and antiproliferative activity against the LoVo cell line in a dose- and time-dependent manner. Flow cytometry analysis demonstrated that PNSE caused cell cycle arrest at S phase. Moreover, PNSE was found to possess antioxidative capacities in the 1,1-diphenyl-2-picrylhydrazyl free radical scavenging assay and hydroxyl radical scavenging assay in vitro. Taken together, the present results suggest that naturally occurring PNSE may provide significant natural defense against human colon cancer. PMID- 22316296 TI - Hijikia fusiforme protects against ovariectomy-induced bone loss in rats. AB - The prophylactic effects of Hijikia fusiforme on bone metabolism were examined using in vitro indices of bone formation and resorption. As the indices of bone formation, osteoblast proliferation and differentiation were measured through mitochondrial enzyme activity [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay] and bone marker alkaline phosphatase (ALP) activity. The aqueous extract of H. fusiforme stimulated the proliferation of the human osteoblast-like cell line MG63 and the ALP activity of the mouse osteoblast like cell line MC3T3-E1. Moreover, extracellular matrix mineralization was accelerated by the addition of H. fusiforme. As the indices of bone resorption, differentiation of the murine macrophage/osteoclast precursor cell line RAW 264.7 by receptor activator of nuclear factor-kappaB ligand (RANKL) was measured as tartrate-resistant acid phosphatase-positive multinucleated cells, which were suppressed by H. fusiforme. Additionally, H. fusiforme lowered the secreted amount of RANKL that is required for the osteoclastic differentiation and activation, but the amount of osteoprotegerin as a decoy receptor for RANKL was not affected. The bone-protective effects of H. fusiforme in estrogen-deficient ovariectomized rats were also investigated. Osteoporosis was induced in female Sprague-Dawley rats by ovariectomy for 15 weeks, and then H. fusiforme was orally administered at a dose of 100 mg/kg of body weight every day for 6 weeks. Bone mineral density in the group orally administered H. fusiforme was increased, compared with ovariectomized rats, but not significantly (P>.05). Oral administration of H. fusiforme improved microarchitecture of bone in terms of bone volume (bone volume/total volume ratio) and trabecular separation (P<.05). The amounts of osteocalcin and C-telopeptide type I collagen in serum were measured as the biomarkers for bone formation and resorption. The level of osteocalcin in serum was increased, but not significantly. However, the level of C-telopeptide type I collagen in serum was significantly decreased (P<.05). When the results are taken together, the present study indicates that H. fusiforme might be useful in the treatment of osteoporosis. PMID- 22316297 TI - Berberine promotes axonal regeneration in injured nerves of the peripheral nervous system. AB - Berberine, an isoquinoline alkaloid component of Coptidis Rhizoma (goldenthread) extract, has been reported to have therapeutic potential for central nervous system disorders such as Alzheimer's disease, cerebral ischemia, and schizophrenia. We have previously shown that berberine promotes the survival and differentiation of hippocampal precursor cells. In a memory-impaired rat model induced by ibotenic acid injection, the survival of pyramidal and granular cells was greatly increased in the hippocampus by berberine administration. In the present study, we investigated the effects of berberine on neurite outgrowth in the SH-SY5Y neuronal cell line and axonal regeneration in the rat peripheral nervous system (PNS). Berberine enhanced neurite extension in differentiating SH SY5Y cells at concentrations of 0.25-3 MUg/mL. In an injury model of the rat sciatic nerve, we examined the neuroregenerative effects of berberine on axonal remyelination by using immunohistochemical analysis. Four weeks after berberine administration (20 mg/kg i.p. once per day for 1 week), the thickness of remyelinated axons improved approximately 1.4-fold in the distal stump of the injury site. Taken together, these results indicate that berberine promotes neurite extension and axonal regeneration in injured nerves of the PNS. PMID- 22316298 TI - Structural and quantitative analysis of antioxidant and low-density lipoprotein antioxidant flavonoids from the grains of sugary rice. AB - Grains of sugary rice were extracted with 80% aqueous methanol, and the concentrated extracts were successively partitioned using ethyl acetate, n butanol, and water. From the n-butanol fractions, four flavonoid glycosides were isolated through repeated silica gel, octadecyl silica gel, and Sephadex LH-20 column chromatographies. Based on the nuclear magnetic resonance, mass spectrometry, and infrared spectroscopic data, the chemical structures of the compounds were determined to be taxifolin-7-O-beta-d-glucopyranoside (1), hyperin (2), isoquercitrin (3), and quercetin gentiobioside (4). These compounds were isolated from the grains of sugary rice for the first time. All isolated compounds were tested for antioxidant activity and low-density lipoprotein (LDL) antioxidative activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and LDL assays. Compound 1 exhibited a strong scavenging effect on DPPH, with a 50% inhibition concentration (IC(50)) value of 8.1 MUM, and also inhibited LDL oxidation with an IC(50) value of 40.0+/-20 MUM. A simple and efficient high-performance liquid chromatography/diode array detection method for the simultaneous determination of the four bioactive flavonoids (1-4) has been developed and applied to their content determination in the sugary rice. The grains were extracted by 80% methanol, and the contents of 1, 2, 3, and 4 were determined to be 1.12+/-0.045, 0.65+/-0.011, 0.68+/-0.032, and 0.89+/-0.021 mg/g, respectively. PMID- 22316299 TI - Association between visceral obesity and sarcopenia and vitamin D deficiency in older Koreans: the Ansan Geriatric Study. AB - OBJECTIVES: To investigate whether vitamin D levels are independently associated with visceral obesity, sarcopenia, or sarcopenic obesity. DESIGN: Cross sectional. SETTING: Population-based sample of elderly adults living in Ansan, Korea. PARTICIPANTS: Two hundred sixteen men and 268 women aged 65 and older. MEASUREMENTS: Serum 25-hydroxyvitamin D (25(OH)D) levels, visceral fat area (VFA) according to abdominal computed tomography scanning, and body composition (body fat percentage, appendicular skeletal muscle mass (ASM)) using dual-energy X-ray absorptiometry. Visceral obesity was defined as VFA of 100 cm(2) or greater and sarcopenia as ASM/height(2) more than 1 standard deviation (SD) below the sex specific mean of a young reference group. RESULTS: The adjusted 25(OH)D level for men was negatively associated with systolic blood pressure, VFA, and body fat percentage but positively associated with ASM. In women, waist circumference, triglyceride levels, and VFA were negatively correlated with 25(OH)D levels. In the joint regression model, VFA and ASM were independently associated with 25(OH)D levels (beta = -0.078, P = .01 and beta = 0.087, P = .02, respectively) per 1SD difference in VFA and ASM in men but not women. When participants were categorized according to four visceral obesity and sarcopenia categories, adjusted mean 25(OH)D level was lower in men with visceral obesity than in men without but was not affected by the presence or absence of sarcopenia. CONCLUSION: Greater visceral fat and lower muscle mass were associated with lower 25(OH)D levels in elderly Korean men, suggesting that screening for vitamin D deficiency may be appropriate in older Koreans with visceral obesity or sarcopenia. Sarcopenic obesity as defined according to prespecified criteria did not have an additive association with 25(OH)D levels. PMID- 22316300 TI - EDS1 contributes to nonhost resistance of Arabidopsis thaliana against Erwinia amylovora. AB - Erwinia amylovora causes fire blight in rosaceous plants. In nonhost Arabidopsis thaliana, E. amylovora triggers necrotic symptoms associated with transient bacterial multiplication, suggesting either that A. thaliana lacks a susceptibility factor or that it actively restricts E. amylovora growth. Inhibiting plant protein synthesis at the time of infection led to an increase in necrosis and bacterial multiplication and reduced callose deposition, indicating that A. thaliana requires active protein synthesis to restrict E. amylovora growth. Analysis of the callose synthase-deficient pmr4-1 mutant indicated that lack of callose deposition alone did not lead to increased sensitivity to E. amylovora. Transcriptome analysis revealed that approximately 20% of the genes induced following E. amylovora infection are related to defense and signaling. Analysis of mutants affected in NDR1 and EDS1, two main components of the defense gene activation observed, revealed that E. amylovora multiplied ten times more in the eds1-2 mutant than in the wild type but not in the ndr1-1 mutant. Analysis of mutants affected in three WRKY transcription factors showing EDS1-dependent activation identified WRKY46 and WRKY54 as positive regulators and WRKY70 as a negative regulator of defense against E. amylovora. Altogether, we show that EDS1 is a positive regulator of nonhost resistance against E. amylovora in A. thaliana and hypothesize that it controls the production of several effective defenses against E. amylovora through the action of WRKY46 and WRKY54, while WRKY70 acts as a negative regulator. PMID- 22316301 TI - Effect of H2S on the circadian rhythm of mouse hepatocytes. AB - BACKGROUND: Dysregulation of circadian rhythms can contribute to diseases of lipid metabolism. NAD-dependent deacetylase sirtuin-1(SIRT1) is an important hub which links lipid metabolism with circadian clock by its deacetylation activity depends on intracellular NAD+/NADH content ratio. Hydrogen sulfide (H2S) is an endogenous reductant which can affect the intracellular redox state. Therefore, we hypothesized that exogenous H2S can affect the expression of circadian clock genes mediated by sirt1 thereby affecting body's lipid metabolism. And also because the liver is a typical peripheral circadian clock oscillator that is intimately linked to lipid metabolism. Thus the effect of H2S were observed on 24 hour dynamic expression of 4 central circadian clock genes and sirt1gene in primary cultured hepatocytes. RESULTS: We established a hepatocyte model that showed a circadian rhythm by serum shock method. And detected that the expression level and the peak of circadian clock genes decreased gradually and H2S could maintain the expression and amplitude of circadian clock genes such as Clock, Per2, Bmal1 and Rev-erbalphawithin a certain period time. Accordingly the expression level of sirt1 in H2S group was significantly higher than that in the control group. CONCLUSION: Exogenous reductant H2S maintain the circadian rhythm of clock gene in isolated liver cells. We speculated that H2S has changed NAD+/NADH content ratio in hepatocytes and enhanced the activity of SIRT1 protein directly or indirectly, so as to maintain the rhythm of expression of circadian clock genes, they play a role in the prevention and treatment of lipid metabolism related disease caused by the biological clock disorders. PMID- 22316302 TI - Dual-functional gadolinium-based copper(II) probe for selective magnetic resonance imaging and fluorescence sensing. AB - A unique gadolinium complex, Nap-DO3A-Gd, comprising a naphthylamine luminescent moiety, a di-2-picolylamine (DPA) binding chelator, and a 1,4,7,10 tetraazacyclododecane-1,4,7-triacetic acid (DO3A) moiety has been designed and synthesized as a dual-functional probe for selective magnetic resonance imaging and fluorescent sensing of copper(II) in living cells. Nap-DO3A-Gd exhibited a turn-on manner of relaxivity changes and a fluorescent quenching toward Cu(2+). Through the introduction of naphthalamide into the Gd(3+) contrast agent platform to restrict the coordination ability of the DPA chelator and with Gd(3+) coordinating to the DPA moiety to turn away the interferences of other metal cations from Cu(2+) detection, the probe featured selective relaxivity changes toward Cu(2+) over other metal ions and brought unique Cu(2+)-specific luminescent responses. The probe was water-soluble with the luminescent detection limit established at 6 ppb and was successfully used for luminescence imaging detection of copper(II) in living cells. The results demonstrated the efficiency and advantage of our approach in the development of a dual-modality image. PMID- 22316303 TI - The influence of early yield on the accumulation of major taste and health related compounds in black and red currant cultivars (Ribes spp.). AB - The focus of our study was to investigate the effect of crop load on the accumulation and composition of primary metabolites (sugars and organic acids), selected groups of flavonoids (anthocyanins and flavonols), and total phenolics in two subsequent years in four black currant cultivars ('Titania', 'Triton', 'Tsema', and 'Cacanska crna') and three red currant cultivars ('Junifer', 'Rolan', and 'Stanza'). For the determination and quantification of compounds, high-performance liquid chromatography-photodiode array with a mass spectrometer was used. Significant differences among cultivars were detected in all analyzed compounds. Anthocyanins were the predominant phenolic group and were more abundant in black currant cultivars as compared to red ones. Similar amounts of sugars and organic acids were measured in both Ribes species; however, vitamin C was 3-fold higher in black currants. A larger crop load in the second year had a negative effect on the sugar content of berries and promoted a higher degree of acids, with the exception of vitamin C, which was higher in the year with a lower crop load. On the other hand, the content of anthocyanins and flavonols was higher in the year with a larger crop load, while there were no differences in total phenolic content. PMID- 22316304 TI - Identify DNA-binding proteins with optimal Chou's amino acid composition. AB - DNA-binding proteins play an important role in most cellular processes, such as gene regulation, recombination, repair, replication, and DNA modification. In this article, an optimal Chou's pseudo amino acid composition (PseAAC) based on physicochemical characters of amino acid is proposed to represent proteins for identifying DNAbinding proteins. Six physicochemical characters of amino acids are utilized to generate the sequence features via the web server PseAAC. The optimal values of two important parameters (correlation factor delta and weighting factor w) about PseAAC are determined to get the appropriate representation of proteins, which ultimately result in better prediction performance. Experimental results on the benchmark datasets using random forest show that our method is really promising to predict DNA-binding proteins and may at least be a useful supplement tool to existing methods. PMID- 22316305 TI - Predicting protein structural class by incorporating patterns of over-represented k-mers into the general form of Chou's PseAAC. AB - Computational prediction of protein structural class based on sequence data remains a challenging problem in current protein science. In this paper, a new feature extraction approach based on relative polypeptide composition is introduced. This approach could take into account the background distribution of a given k-mer under a Markov model of order k-2, and avoid the curse of dimensionality with the increase of k by using a T-statistic feature selection strategy. The selected features are then fed to a support vector machine to perform the prediction. To verify the performance of our method, jackknife cross validation tests are performed on four widely used benchmark datasets. Comparison of our results with existing methods shows that our method provides satisfactory performance for structural class prediction. PMID- 22316306 TI - Influence of truncation of avian beta-defensin-4 on biological activity and peptide-membrane interaction. AB - Defensins are important components in host defense systems. The therapeutic use of beta-defensins is limited by their innate toxicity and high cost due to the size and complex disulfide pairing. In this study, we used linear avian beta- defensin-4 (RL38) without disulfide bonds as model peptide to derive two peptides by the truncation. GL23 is the C-terminal truncated sequence of RL38, and GLI23 is the derivative of GL23 by the replacement of cysteines with isoleucines. Results showed that these peptides exhibited strong antibacterial activity against gram-negative and gram-positive bacteria. An exception was that GL23 showed weak antimicrobial activity against gallinaceous pathogenic bacteria Salmonella Pullorum C79-13. Two truncated peptides GL23 and GLI23 displayed no or weak hemolysis, which was in accordance with little blue shifts of the peptides in the presence of synthetic eukaryotic membranes. CD spectroscopy demonstrated that these peptides appeared to be unfolded in aqueous solution but acquire structure in the presence of membrane- mimicking phospholipids. GLI23 kept the antibacterial activity at high concentrations of NaCl or low concentration of divalent cations (Mg2+ and Ca2+). The peptides preferentially bound to negatively charged phospholipids over zwitterionic phospholipids, which led to greater cell selectivity. The outer and inner membranes assay displayed that GLI23 killed bacteria by targeting the cell membrane. These results suggest the peptides derived by truncation of linear beta-defensins may be a promising candidate for future antibacterial agent. PMID- 22316307 TI - pH-sensitive self-associations of the N-terminal domain of NBCe1-A suggest a compact conformation under acidic intracellular conditions. AB - NBCe1-A is an integral membrane protein that cotransports Na+ and HCO3 - ions across the basolateral membrane of the proximal tubule. It is essential for maintaining a homeostatic balance of cellular and blood pH. In X-ray diffraction studies, we reported that the cytoplasmic, N-terminal domain of NBCe1-A (NtNBCe1 A) is a dimer. Here, biophysical measurements show that the dimer is in a concentration-dependent dynamic equilibrium among three additional states in solution that are characterized by its hydrodynamic properties, molar masses, emission spectra, binding properties, and stabilities as a function of pH. Under physiological conditions, dimers are in equilibrium with monomers that are pronounced at low concentration and clusters of molecular masses up to 3-5 times that of a dimer that are pronounced at high concentration. The equilibrium can be influenced so that individual dimers predominate in a taut conformation by lowering the pH. Conversely, dimers begin to relax and disassociate into an increasing population of monomers by elevating the pH. A mechanistic diagram for the inter-conversion of these states is given. The self-associations are further supported by surface plasmon resonance (SPR-Biacore) techniques that illustrate NtNBCe1-A molecules transiently bind with one another. Bicarbonate and bicarbonate-analog bisulfite appear to enhance dimerization and induce a small amount of tetramers. A model is proposed, where the Nt responds to pH or bicarbonate fluctuations inside the cell and plays a role in self-association of entire NBCe1-A molecules in the membrane. PMID- 22316308 TI - Production of recombinant oxytocin through sulfitolysis of inteincontaining fusion protein. AB - An artificial gene consisting of seven copies of an oxytocinoyl-lysine encoding sequence arranged in a tandem was synthesized and inserted downstream of the SspDnaB intein gene in a pTWIN1 plasmid. The corresponding fusion protein Dnab 7oxy contained 16 cysteine residues and formed inclusion bodies when expressed in E. coli. The standard protocol involving solubilization of the fusion protein and its autocatalytic cleavage on a chitin resin was not effective because of a very low yield of the cleavage reaction. Attempts to perform a refolding of the intein part of the fusion protein in solution were also unsuccessful because of a high level of protein aggregation. Sulfitolysis of cysteine residues is known to increase a solubility of proteins and peptides. Therefore we suggested a one-step approach that combines solubilization of inclusion bodies and sulfitolysis of a hybrid protein. The fusion protein was completely reduced and solubilized in 8M urea at pH 9.0 in the presence of sodium sulfite and sodium tetrathionate. The sulfitized protein was loaded onto a chitin column, an efficient cleavage was induced by a pH shift from 9.0 to 6.5, and seven successively connected oxytocinoyl- lysine units were released. The heptamer was subjected to trypsinolysis yielding sulfitized monomers of oxytocinoyllysine. Oxytocinoyl lysine was refolded as described previously and treated by carboxypeptidase B to form the oxytocinic acid. The target oxytocin amide was then synthesized via methyl ester intermediate. Using this approach 6 mg of recombinant oxytocin can be obtained from 1 g of biomass. PMID- 22316309 TI - A simple and universal method to express protein in unfused form. AB - The effect of additional amino acid residue(s) fused to the N- and/or C-terminal on properties of the heterogeneously expressed protein is usually difficult to be predicted. Recombinant proteins expressed without any fused sequence should be the most desired materials for related studies, such as protein drug preparation, biochemistry investigations. Here, we report a very simple and universal method enabling the expression of protein in its unfused form between the same two restriction enzyme sites (at a higher level) if a plasmid can support the fused expression. The method provided an assessable solution for unfused expression without increase in experimental resource; the necessary material is an additional primer. The method is especially useful for making whole-cell biocatalyst in which no purification steps are required. PMID- 22316310 TI - Prediction of nicotinamide adenine dinucleotide interacting sites based on ensemble support vector machine. AB - Nicotinamide adenine dinucleotide (NAD) plays an important role in cellular metabolism and acts as hydrideaccepting and hydride-donating coenzymes in energy production. Identification of NAD protein interacting sites can significantly aid in understanding the NAD dependent metabolism and pathways, and it could further contribute useful information for drug development. In this study, a computational method is proposed to predict NAD-protein interacting sites using the sequence information and structure-based information. All models developed in this work are evaluated using the 7-fold cross validation technique. Results show that using the position specific scoring matrix (PSSM) as an input feature is quite encouraging for predicting NAD interacting sites. After considering the unbalance dataset, the ensemble support vector machine (SVM), which is an assembly of many individual SVM classifiers, is developed to predict the NAD interacting sites. It was observed that the overall accuracy (Acc) thus obtained was 87.31% with Matthew's correlation coefficient (MCC) equal to 0.56. In contrast, the corresponding rate by the single SVM approach was only 80.86% with MCC of 0.38. These results indicated that the prediction accuracy could be remarkably improved via the ensemble SVM classifier approach. PMID- 22316311 TI - Epitope mapping and identification of amino acids critical for rabbits IgG binding to linear epitopes on buffalo beta-lactoglobulin. AB - Buffalo milk safety was highlighted with the increase in dietary consumption, and a little information is available on buffalo milk allergy except for cross reactivity between buffalo and cow milk. In this work, linear epitopes and critical amino acids of buffalo beta-lactoglobulin were defined by 4 rabbit's sera using SPOTTM peptide arrays approach based on the defined mimotopes. The eight epitopes on buffalo beta-lactoglobulin were located in the position of A6(21-30), A7(25-34), A8 (29-38), B4 (73-82), B5(77-86), C(87-96), F4(134-143) and F8(150-159), respectively. Among them, four epitopes (A7, A8, F4 and F8) were described as the most major epitopes and peptide (A6, B4, B5 and C) as the second major epitopes. Following single AA substitutions (Alanine or Glycine) at each position of the major epitopes, 2,3,2,3,5 and 3 of critical amino acids were identified on epitopes of A6, A8, B5, C , F4 and F8, respectively, which vary in distribution among the epitopes, such as in C terminal or N terminal and in continuous or discontinuous forms, characteristics including hydrophobicity, polar and charge, and existed frequency. PMID- 22316312 TI - Identifying GPCRs and their types with Chou's pseudo amino acid composition: an approach from multi-scale energy representation and position specific scoring matrix. AB - G-protein coupled receptor (GPCR) is a membrane protein family, which serves as an interface between cell and the outside world. They are involved in various physiological processes and are the targets of more than 50% of the marketed drugs. The function of GPCRs can be known by conducting Biological experiments. However, the rapid increase of GPCR sequences entering into databanks, it is very time consuming and expensive to determine their function based only on experimental techniques. Hence, the computational prediction of GPCRs is very much demanding for both pharmaceutical and educational research. Feature extraction of GPCRs in the proposed research is performed using three techniques i.e. Pseudo amino acid composition, Wavelet based multi-scale energy and Evolutionary information based feature extraction by utilizing the position specific scoring matrices. For classification purpose, a majority voting based ensemble method is used; whose weights are optimized using genetic algorithm. Four classifiers are used in the ensemble i.e. Nearest Neighbor, Probabilistic Neural Network, Support Vector Machine and Grey Incidence Degree. The performance of the proposed method is assessed using Jackknife test for a number of datasets. First, the individual performances of classifiers are assessed for each dataset using Jackknife test. After that, the performance for each dataset is improved by using weighted ensemble classification. The weights of ensemble are optimized using various runs of Genetic Algorithm. We have compared our method with various other methods. The significance in performance of the proposed method depicts it to be useful for GPCRs classification. PMID- 22316313 TI - Investigating hypercoagulability during treatment for immune-mediated thrombocytopenia: a pilot study. AB - BACKGROUND: Thromboembolism has recently been described as a complication following treatment for idiopathic thrombocytopenic purpura (ITP). This pilot study was undertaken to determine whether dogs suffering from ITP experience hypercoagulability during treatment and recovery. STUDY DESIGN: Thromboelastograms (TEG) were performed on dogs with ITP within 24 hours of admission to the hospital, the first day the platelet count exceeded 40 * 10(9) /L (Day 1), and on Days 4, 7, and 14. KEY FINDINGS: All dogs had hypocoagulable TEG tracings on initial admission to the hospital, but developed TEG tracings suggestive of hypercoagulability during the study period as indicated by increased maximum amplitude. SIGNIFICANCE: Dogs with ITP developed changes on TEG consistent with hypercoagulability during the study period. Many factors are likely to contribute to these changes. The clinical risk of thrombosis in these patients is unknown. PMID- 22316314 TI - Efficacy of vitamin D supplementation in multiple sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial. AB - BACKGROUND: Multiple sclerosis is the most common chronic inflammatory disease of the central nervous system in young adults. Despite the fact that numerous lines of evidence link both the risk of disease development and the disease course to the serum level of 25-hydroxyvitamin D it still remains elusive whether multiple sclerosis patients benefit from boosting the serum level of 25-hydroxyvitamin D, mainly because interventional clinical trials that directly address the therapeutic effects of vitamin D in multiple sclerosis are sparse. We here present the protocol of an interventional clinical phase II study to test the hypothesis, that high-dose vitamin D supplementation of multiple sclerosis patients is safe and superior to low-dose supplementation with respect to beneficial therapeutic effects. METHODS/DESIGN: The EVIDIMS trial is a German multi-center, stratified, randomized, controlled and double-blind clinical phase II pilot study. Eighty patients with the diagnosis of definite multiple sclerosis or clinically isolated syndrome who are on a stable immunomodulatory treatment with interferon-beta1b will be randomized to additionally receive either high dose (average daily dose 10.200 IU) or low-dose (average daily dose 200 IU) cholecalciferol for a total period of 18 months. The primary outcome measure is the number of new lesions detected on T2-weighted cranial MRI at 3 tesla. Secondary endpoints include additional magnetic resonance imaging and optical coherence tomography parameters for neuroinflammation and -degeneration, clinical parameters for disease activity, as well as cognition, fatigue, depression, and quality of life. Safety and tolerability of high-dose vitamin D supplementation are further outcome parameters. DISCUSSION: In light of the discrepancy between existing epidemiological and preclinical data on the one hand and available clinical data on the other the EVIDIMS trial will substantially contribute to the evaluation of the efficacy of high-dose vitamin D supplementation in MS patients. The study design presented here fulfills the criteria of a high-quality clinical phase II trial in MS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01440062. PMID- 22316315 TI - Comparison of vaginal gel isoflavones versus no topical treatment in vaginal dystrophy: results of a preliminary prospective study. AB - OBJECTIVE: Vaginal dystrophy due to hypo-oestrogenism takes advantage of local and systemic oestrogens to balance the vaginal ecosystem and improve tissue hydration. Women who do not accept/tolerate hormone therapy can use intravaginal isoflavones to relieve vaginal dryness. The aim of this study was to investigate the clinical effect of a vaginal gel formulation containing isoflavones compared with no topical treatment in women with vaginal dystrophy. MATERIAL AND METHODS: In a multicentre, controlled, parallel-group study, menopausal women with vaginal dystrophy were randomized to vaginal gel (EG) or no topical treatment (NT) for 4 weeks. EG contained isoflavones, Lactobacillus sporogenes, Calendula officinalis extract and lactic acid (Estromineral Gel, Rottapharm-Madaus). All patients received daily oral isoflavones plus L. sporogenes. Clinical evaluations were performed at time 0, 2 and 4 weeks. RESULTS: 186 women were recruited, 103 in the EG group and 83 in the NT group, mean age 53.7 years, postmenopausal for 4.1 years. The severity of itching, burning, vulvovaginal erythema, vaginal dryness and dyspareunia were significantly reduced during EG treatment compared with the NT group. CONCLUSIONS: The combination of oral and topical isoflavones was shown to be more effective than oral treatment alone in reducing the problems of postmenopausal vaginal dystrophy. PMID- 22316316 TI - Size and support effects for the water-gas shift catalysis over gold nanoparticles supported on model Al2O3 and TiO2. AB - The water-gas shift (WGS) reaction rate per total mole of Au under 7% CO, 8.5% CO(2), 22% H(2)O, and 37% H(2) at 1 atm for Au/Al(2)O(3) catalysts at 180 degrees C and Au/TiO(2) catalysts at 120 degrees C varies with the number average Au particle size (d) as d(-2.2+/-0.2) and d(-2.7+/-0.1), respectively. The use of nonporous and crystalline, model Al(2)O(3) and TiO(2) supports allowed the imaging of the active catalyst and enabled a precise determination of the Au particle size distribution and particle shape using transmission electron microscopy (TEM). Further, the apparent reaction orders and the stretching frequency of CO adsorbed on Au(0) (near 2100 cm(-1)) determined by diffuse reflectance infrared spectroscopy (DRIFTS) depend on d. Because of the changes in reaction rates, kinetics, and the CO stretching frequency with number average Au particle size, it is determined that the dominant active sites are the low coordinated corner Au sites, which are 3 and 7 times more active than the perimeter Au sites for Au/Al(2)O(3) and Au/TiO(2) catalysts, respectively, and 10 times more active for Au on TiO(2) versus Al(2)O(3). From operando Fourier transform infrared spectroscopy (FTIR) experiments, it is determined that the active Au sites are metallic in nature. In addition, Au/Al(2)O(3) catalysts have a higher apparent H(2)O order (0.63) and lower apparent activation energy (9 kJ mol(-1)) than Au/TiO(2) catalysts with apparent H(2)O order of -0.42 to -0.21 and activation energy of 45-60 kJ mol(-1) at near 120 degrees C. From these data, we conclude that the support directly participates by activating H(2)O molecules. PMID- 22316317 TI - Direct intercalation of bis-2,2',2",6-terpyridylcobalt(III) into zirconium phosphate layers for biosensing applications. AB - The direct intercalation reaction of [Co(tpy)(2)](2+) with the highly hydrated theta phase of layered zirconium phosphate (theta-ZrP) resulted in the formation of the oxidized [Co(tpy)(2)](3+) ion within the ZrP material. The X-ray powder diffraction patterns showed that the interlayer distance increases from 10.3 A in theta-ZrP to 14.9 A in the dry [Co(tpy)(2)](3+)-intercalated ZrP {[Co(tpy)(2)](3+):ZrP} phase. The complex remains electroactive within the layers of ZrP. The formal potential of a carbon paste electrode (CPE) modified with [Co(tpy)(2)](3+):ZrP (E degrees ' = 40.8 mV versus Ag/AgCl, 3.5 M NaCl) is non-pH dependent. However, the sensitivity of the [Co(tpy)(2)](3+):ZrP-modified CPE for the detection of reduced nicotinamide adenine dinucleotide (NADH) electrooxidation was lower than that of a previously reported CPE modified with [Ru(phend)(2)bpy](2+)-intercalated ZrP. (1) To improve the characteristics of NADH electrooxidation of the [Co(tpy)(2)](3+):ZrP-modified CPE, we included the enzyme diaphorase in solution, which increased the electrocatalytic current for NADH oxidation. A bienzymatic lactate biosensor was constructed and used for lactate sensing. PMID- 22316318 TI - Human attitudes towards herpetofauna: the influence of folklore and negative values on the conservation of amphibians and reptiles in Portugal. AB - BACKGROUND: Human values and folklore of wildlife strongly influence the effectiveness of conservation efforts. These values and folklore may also vary with certain demographic characteristics such as gender, age, or education. Reptiles and amphibians are among the least appreciated of vertebrates and are victims of many negative values and wrong ideas resulting from the direct interpretation of folklore. We try to demonstrate how these values and folklore can affect the way people relate to them and also the possible conservation impacts on these animals. METHODS: A questionnaire survey distributed to 514 people in the district of Evora, Portugal, was used to obtain data regarding the hypothesis that the existence of wrong ideas and negative values contributes to the phenomenon of human-associated persecution of these animals. A structural equation model was specified in order to confirm the hypothesis about the possible relationships between the presence of perceptions and negative values about amphibians and reptiles and persecution and anti-conservation attitudes. Sociodemographic variables were also added. RESULTS: The results of the model suggest that the presence of folklore and negative values clearly predicts persecution and anti-conservation attitudes towards amphibians and reptiles. Also, the existence of folklore varies sociodemographically, but negative values concerning these animals are widespread in the population. CONCLUSIONS: With the use of structural equation models, this work is a contribution to the study of how certain ideas and values can directly influence human attitudes towards herpetofauna and how they can be a serious conservation issue. PMID- 22316319 TI - Trends in incidence of oral and pharyngeal carcinoma in Florida: 1981-2008. AB - OBJECTIVE: While the overall incidence rates of oral and pharyngeal squamous cell carcinoma (SCC) have decreased in the United States, there is evidence of increasing incidence at selected anatomic sites, particularly among younger adults. The objective of this study was to examine trends in incidence rates of oral and pharyngeal cancers in Florida. METHODS: Using data from the Florida Cancer Data System, we examined the incidence of oral and pharyngeal carcinomas in Florida from 1981 through 2008. Factors of interest included sex, race, and trends over time. Percent change (PC) and annual percent change (APC) were computed to characterize trends over time. RESULTS: A total of 53,648 cases of oral or pharyngeal cancer were identified from 1981 through 2008. Significant increasing trends were observed only for pharyngeal cancers in males, with significant decreasing trends for pharyngeal cancer in females and oral cancer for both sexes. For tonsil and base of tongue cancers, increasing trends were detected for white males only. Further investigation among white males showed that, except for base of tongue cancer in the 20-44 age group, the incidence of both cancers increased across all age groups, with the largest increase for both sites found in the 45-64 age group. CONCLUSIONS: This study supports the finding of increasing incidence of SCC of the tonsil and base of tongue in males, in contrast to decreasing trends for most oral and pharyngeal carcinomas. However, we observed that this increase occurred in white males only and the most dramatic increase occurred in the 45-64 age group. PMID- 22316321 TI - Herbal medicines for the prevention and treatment of Alzheimer's disease. AB - Alzheimer's disease (AD) is a chronic neurodegenerative disorder and is the most common cause of progressive dementia in aging. Research on AD therapy has been partly successful in terms of developing symptomatic treatments, but there have been a number of failures with regard to developing disease-modifying therapies. The pathogenesis of AD remains unclear and the present one-drug, one-target paradigm for anti-AD treatment appears to be clinically unsuccessful. In many countries, traditional herbal medicines are used to prevent or treat neurodegenerative disorders, and some have been developed as nutraceuticals or functional foods. This review briefly introduces progress in the development of anti-AD treatments and then focuses on recent advances in the research, characteristics, and development of herbal medicines. Because AD arises via multiple pathological or neurotoxic pathways, herbal medicines have the potential to be developed into optimum pharmaceuticals and nutraceuticals for AD because of their multi-function, multi-target characteristics. PMID- 22316320 TI - Dysfunction of the RAR/RXR signaling pathway in the forebrain impairs hippocampal memory and synaptic plasticity. AB - BACKGROUND: Retinoid signaling pathways mediated by retinoic acid receptor (RAR)/retinoid * receptor (RXR)-mediated transcription play critical roles in hippocampal synaptic plasticity. Furthermore, recent studies have shown that treatment with retinoic acid alleviates age-related deficits in hippocampal long term potentiation (LTP) and memory performance and, furthermore, memory deficits in a transgenic mouse model of Alzheimer's disease. However, the roles of the RAR/RXR signaling pathway in learning and memory at the behavioral level have still not been well characterized in the adult brain. We here show essential roles for RAR/RXR in hippocampus-dependent learning and memory. In the current study, we generated transgenic mice in which the expression of dominant-negative RAR (dnRAR) could be induced in the mature brain using a tetracycline-dependent transcription factor and examined the effects of RAR/RXR loss. RESULTS: The expression of dnRAR in the forebrain down-regulated the expression of RARbeta, a target gene of RAR/RXR, indicating that dnRAR mice exhibit dysfunction of the RAR/RXR signaling pathway. Similar with previous findings, dnRAR mice displayed impaired LTP and AMPA-mediated synaptic transmission in the hippocampus. More importantly, these mutant mice displayed impaired hippocampus-dependent social recognition and spatial memory. However, these deficits of LTP and memory performance were rescued by stronger conditioning stimulation and spaced training, respectively. Finally, we found that pharmacological blockade of RARalpha in the hippocampus impairs social recognition memory. CONCLUSIONS: From these observations, we concluded that the RAR/RXR signaling pathway greatly contributes to learning and memory, and LTP in the hippocampus in the adult brain. PMID- 22316322 TI - Short-term oral nutritional intervention with protein and vitamin D decreases falls in malnourished older adults. AB - OBJECTIVES: To evaluate the effects of a short-term nutritional intervention with protein and vitamin D on falls in malnourished older adults. DESIGN: Randomized controlled trial. SETTING: From hospital admission until 3 months after discharge. PARTICIPANTS: Malnourished older adults (>= 60) newly admitted to an acute hospital (n = 210). INTERVENTION: Participants were randomized to receive nutritional intervention (energy- and protein-enriched diet, oral nutritional supplements, calcium-vitamin D supplement, telephone counseling by a dietitian) for 3 months after discharge or usual care. MEASUREMENTS: Number of participants who fell, fall incidents, serum 25-hydroxyvitamin D, and dietary intake. Measurements were performed on admission to hospital and 3 months after discharge. RESULTS: Three months after discharge, 10 participants (10%) in the intervention group had fallen at least once, compared with 24 (23%) in the control group (hazard ratio = 0.41, 95% confidence interval (CI) = 0.19-0.86). There were 57 fall incidents (16 in the intervention group; 41 in the control group). A significantly higher intake of energy (280 kcal, 95% CI = 37-524 kcal) and protein (11 g, 95% CI = 1-25 g) and significantly higher serum 25 hydroxyvitamin D levels (10.9 nmol/L, 95% CI = 2.9-18.9 nmol/L) were found in participants in the intervention group than in controls. CONCLUSION: A short-term nutritional intervention consisting of oral nutritional supplements and calcium and vitamin D supplementation and supported by dietetic counseling in malnourished older adults decreases the number of patients who fall and fall incidents. PMID- 22316323 TI - Prasugrel versus clopidogrel antiplatelet therapy after acute coronary syndrome: matching treatments with patients. AB - Antithrombotic therapy is imperative in the management of patients presenting with an acute coronary syndrome (ACS). The combination of antiplatelet therapy in conjunction with antithrombotic therapy has become the standard of care in improving the morbidity and mortality of patients with an ACS and in reducing ischemic complications of percutaneous coronary intervention. Patients with an ACS are at increased risk for a recurrent event, both in-hospital and for several months afterward. Secondary prevention to reduce these events is accomplished through the establishment of appropriate medical therapy. Dual antiplatelet therapy with aspirin and adenosine 5'-diphosphate P2Y(12) receptor blockers such as ticlopidine or clopidogrel are integral components of this regimen; however, both of these thienopyridines have a relatively slow onset of action and variable bioavailability. Prasugrel, a third-generation thienopyridine approved by the US FDA in 2009, has a more rapid onset of platelet inhibition than clopidogrel and ticlopidine because of increased efficiency of prodrug-to-active metabolite conversion. The result is higher and less variable concentration of the active metabolite within 60 minutes following oral dosing. Phase II and III trials assessing the safety and efficacy of prasugrel have been completed, including JUMBO-TIMI 26, PRINCIPLE-TIMI 44, and TRITON-TIMI 38. These trials demonstrated greater inhibition of platelet aggregation and lower rates of the composite endpoint of death, non-fatal myocardial infarction, and stroke compared with clopidogrel. However, major bleeding occurred more frequently with prasugrel treatment than with clopidogrel. This review highlights the current state of evidence-based antiplatelet therapy and provides guidance on appropriate use of prasugrel in cardiovascular medicine. PMID- 22316324 TI - Lack of inhibitory effect of acetylsalicylic acid and meloxicam on whole blood platelet aggregation in cats. AB - OBJECTIVE: To determine the effects of acetylsalicylic acid (ASA) and meloxicam on feline platelet aggregation and associated platelet thromboxane production and serotonin release. DESIGN: Prospective interventional study. SETTING: University research facility. ANIMALS: Eight healthy male castrated domestic short hair cats from a research colony. INTERVENTIONS: Oral medications were administered to 8 cats for 14 days in a randomized, placebo-controlled, crossover design. Treatment groups included: aspirin (ASA) (5 mg/kg q 48 h), meloxicam (0.05 mg/kg q 24 h), and placebo (0.5 mL of water q 24 h). Thromboxane assays (TXB(2) ) and whole blood (impedance) aggregometry (WBA) were performed on samples collected before drug administration, and on days 7, 15, and 17, using adenosine diphosphate (ADP; 10 MUM) and collagen (5 MUg/mL) as agonists for WBA. Serotonin release was assayed on postaggregation plasma. Oral mucosal bleeding time (OMBT) and complete blood cell counts were measured on days 0 and 15. MEASUREMENTS AND MAIN RESULTS: Neither medication affected WBA at any time point. OMBT decreased in the ASA group relative to baseline. No differences were detected in WBA and OMBT baseline between any groups. No difference was detected in serotonin secretion at any time point. TXB(2) was significantly decreased in the ASA group at all times after initiation of treatment but no change was noted in the meloxicam or placebo groups. CONCLUSIONS: At the doses studied, neither meloxicam nor ASA had an inhibitory effect on WBA or OMBT in cats. Thromboxane concentrations were significantly decreased with ASA treatment. PMID- 22316326 TI - Cutaneous bacillary angiomatosis in renal transplant recipients: report of three new cases and literature review. AB - Bacillary angiomatosis (BA) is a rare vasculoproliferative disorder due to Bartonella henselae (BH) or Bartonella quintana. It can involve many organs, including the skin, and has been mainly reported in patients with acquired immunodeficiency syndrome. In organ transplant recipients (OTR), this disorder remains misdiagnosed and therapeutic guidelines are nonexistent. We report 3 cases of BA with skin involvement in OTR and review similar cases from the literature. BA manifests on the skin with violaceous lesions mimicking Kaposi sarcoma, and is associated with fever, lymphadenopathy, and liver, spleen, or lung nodules. Bartonellosis infections in OTR are due to BH, the agent causing cat-scratch disease (CSD), but BA comprises histologically a prominent vascular proliferation, which is usually lacking in CSD. Cultures and serologic tests are poorly reliable for the diagnosis, which relies on demonstration of BH within the lesions. A history of cat exposure exists in most cases and pediatric OTR are at higher risk. Prevention consists of regular use of a flea-control product in cats and prompt cleaning of scratches. Our cases highlight several original features of this rare condition, which could potentially improve the management of BA in OTR. PMID- 22316327 TI - Primary small cell carcinoma of the pancreas: rare type of pancreatic cancer and review of the literatures. AB - BACKGROUND: Primary small cell carcinoma of the pancreas (SCCP) is a rare malignancy with an extremely poor prognosis which accounts for 1 to 1.4 percent of all pancreatic malignancies. CASE PRESENTATION: We present the case of a 62 year-old man with a half-month history of upper abdominal discomfort who was diagnosed with SCC of the pancreatic tail. A Chest X-ray showed no evidence of primary lung tumor. The diagnosis of a SCCP was confirmed by post-surgery pathology and immunohistology. In our review of the published reports of SCCP, we only found a few cases reported in the literatures. The diagnosis of SCCP needs the post-surgery pathology and immunohistology and the prognosis of SCCP is extremely poor. There was a significant increase in median survival, from 1 to 6 months, in treated patients compared to patients treated only by symptomatic management. Chemotherapy was the most common treatment and the combination of cisplatin/etoposide was most frequently prescribed. CONCLUSION: The accurate diagnosis of (SCCP) is necessary for determining prognosis and deciding appropriate therapy. PMID- 22316330 TI - Metal-oxide nanoparticles increase the bactericidal effect of blue light. PMID- 22316329 TI - Chronic fatigue syndrome after Giardia enteritis: clinical characteristics, disability and long-term sickness absence. AB - BACKGROUND: A waterborne outbreak of Giardia lamblia gastroenteritis led to a high prevalance of long-lasting fatigue and abdominal symptoms. The aim was to describe the clinical characteristics, disability and employmentloss in a case series of patients with Chronic Fatigue Syndrome (CFS) after the infection. METHODS: Patients who reported persistent fatigue, lowered functional capacity and sickness leave or delayed education after a large community outbreak of giardiasis enteritis in the city of Bergen, Norway were evaluated with the established Centers for Disease Control and Prevention criteria for CFS. Fatigue was self-rated by the Fatigue Severity Scale (FSS). Physical and mental health status and functional impairment was measured by the Medical Outcome Severity Scale-short Form-36 (SF-36). The Hospital Anxiety and Depression Scale (HADS) was used to measure co-morbid anxiety and depression. Inability to work or study because of fatigue was determined by sickness absence certified by a doctor. RESULTS: A total of 58 (60%) out of 96 patients with long-lasting post-infectious fatigue after laboratory confirmed giardiasis were diagnosed with CFS. In all, 1262 patients had laboratory confirmed giardiasis. At the time of referral (mean illness duration 2.7 years) 16% reported improvement, 28% reported no change, and 57% reported progressive course with gradual worsening. Mean FSS score was 6.6. A distinctive pattern of impairment was documented with the SF-36. The physical functioning, vitality (energy/fatigue) and social functioning were especially reduced. Long-term sickness absence from studies and work was noted in all patients. CONCLUSION: After giardiasis enteritis at least 5% developed clinical characteristics and functional impairment comparable to previously described post infectious fatigue syndrome. PMID- 22316331 TI - Interfacial properties and iron binding to bacterial proteins that promote the growth of magnetite nanocrystals: X-ray reflectivity and surface spectroscopy studies. AB - Surface sensitive X-ray scattering and spectroscopic studies have been conducted to determine structural properties of Mms6, the protein in Magnetospirillum magneticum AMB-1 that is implicated as promoter of magnetite nanocrystals growth. Surface pressure versus molecular area isotherms indicate Mms6 forms stable monolayers at the aqueous/vapor interface that are strongly affected by ionic conditions of the subphase. Analysis of X-ray reflectivity from the monolayers shows that the protein conformation at the interface depends on surface pressure and on the presence of ions in the solutions, in particular of iron ions and its complexes. X-ray fluorescence at grazing angles of incidence from the same monolayers allows quantitative determination of surface bound ions to the protein showing that ferric iron binds to Mms6 at higher densities compared to other ions such as Fe(2+) or La(3+) under similar buffer conditions. PMID- 22316332 TI - Stevioside enhances satellite cell activation by inhibiting of NF-kappaB signaling pathway in regenerating muscle after cardiotoxin-induced injury. AB - Stevioside, a noncaloric sweetener isolated from Stevia rebaudiana, exhibits anti inflammatory and immunomodulatory effects through interference of nuclear factor (NF)-kappa B pathway. We investigated whether this anti-inflammatory property of stevioside could improve muscle regeneration following cardiotoxin-induced muscle injury. Adult male Wistar rats received stevioside orally at an accepted daily dosage of 10 mg kg-1 for 7 days before cardiotoxin injection at the tibialis anterior (TA) muscle of the right hindlimb (the left hindlimb served as control), and stevioside administration was continued for 3 and 7 days. TA muscle was examined at days 3 and 7 postinjury. Although stevioside treatment had no significant effect in enhancing muscle regeneration as indicated by the absence of decreased muscle inflammation or improved myofibrillar protein content compared with vehicle treated injured group at day 7 postinjury, the number of MyoD-positive nuclei were increased (P < 0.05), with a corresponding decrease in NF-kappaB nuclear translocation (P < 0.05). This is the first study to demonstrate that stevioside could enhance satellite cell activation by modulation of the NF-kappaB signaling pathway in regenerating muscle following injury. Thus, stevioside may be beneficial as a dietary supplementation for promoting muscle recovery from injury. However, its pharmacological effect on muscle function recovery warrants further investigation. PMID- 22316333 TI - Quantum behavior of graphene transistors near the scaling limit. AB - The superior intrinsic properties of graphene have been a key research focus for the past few years. However, external components, such as metallic contacts, serve not only as essential probing elements, but also give rise to an effective electron cavity, which can form the basis for new quantum devices. In previous studies, quantum interference effects were demonstrated in graphene heterojunctions formed by a top gate. Here phase coherent transport behavior is demonstrated in a simple two terminal graphene structure with clearly resolved Fabry-Perot oscillations in sub-100 nm devices. By aggressively scaling the channel length down to 50 nm, we study the evolution of the graphene transistor from the channel-dominated diffusive regime to the contact-dominated ballistic regime. Key issues such as the current asymmetry, the question of Fermi level pinning by the contacts, the graphene screening determining the heterojunction barrier width, the scaling of minimum conductivity, and of the on/off current ratio are investigated. PMID- 22316334 TI - Comparing the administration of fentanyl 1 ug kg-1 and fentanyl 0.5 ug kg-1 in dilation and curettage procedures. AB - PURPOSE: This study was carried out to compare fentanyl 0.5 ug kg-1 -propofol as opposed to fentanyl 1 ug kg-1 -propofol in terms of providing adequate analgesia, and a comparable recovery profile in dilation and curettage (D&C) procedures. METHODS: Verbal Pain Scale (VPS) scores, modified Aldrete scores, and hemodynamic parameters were recorded during and after the surgical procedure. In addition, a record was also kept of adverse events, and patients and surgeons were questioned about their satisfaction with the anesthesia. RESULTS: No difference was found between the two groups in terms of hemodynamic parameters, the VPS scores, or patient and surgeon satisfaction. The fentanyl 0.5 ug group displayed significantly higher modified Aldrete scores at both 5- and 10-min postoperative. Adverse events in both groups were considerably few. The incidence of postoperative nausea and vomiting (PONV) in the fentanyl 0.5 ug group was lower eventhough it did not reach the statistically significance level. In addition, faster recovery times were recorded with the administration of fentanyl 0.5 ug kg 1 . CONCLUSION: Fentanyl 0.5 ug kg-1 appears to be as reliable as that of fentanyl 1 ug kg-1 with faster recovery times when used in D&C procedures. PMID- 22316335 TI - Synthesis, characterization, and glutathionylation of cobalamin model complexes [Co(N4PyCO2Me)Cl]Cl2 and [Co(Bn-CDPy3)Cl]Cl2. AB - Synthetic Co(III) complexes containing N5 donor sets undergo glutathionylation to generate biomimetic species of glutathionylcobalamin (GSCbl), an important form of cobalamin (Cbl) found in nature. For this study, a new Co(III) complex was synthesized derived from the polypyridyl pentadentate N5 ligand N4PyCO(2)Me (1). The compound [Co(N4PyCO(2)Me)Cl]Cl(2) (3) was characterized by X-ray crystallography, UV-vis, IR, (1)H NMR, and (13)C NMR spectroscopies and mass spectrometry (HRMS). Reaction of 3 with glutathione (GSH) in H(2)O generates the biomimetic species [Co(N4PyCO(2)Me)(SG)](2+) (5), which was generated in situ and characterized by UV-vis and (1)H NMR spectroscopies and HRMS. (1)H NMR and UV-vis spectroscopic data are consistent with ligation of the cysteine thiolate of GSH to the Co(III) center of 5, as occurs in GSCbl. Kinetic analysis indicated that the substitution of chloride by GS(-) occurs by a second-order process [k(1) = (10.1 +/- 0.7) * 10(-2) M(-1) s(-1)]. The observed equilibrium constant for formation of 5 (K(obs) = 870 +/- 50 M(-1)) is about 3 orders of magnitude smaller than for GSCbl. Reaction of the Co(III) complex [Co(Bn-CDPy3)Cl]Cl(2) (4) with GSH generates glutathionylated species [Co(Bn-CDPy3)(GS)](2+) (6), analogous to 5. Glutathionylation of 4 occurs at a similar rate [k(2) = (8.4 +/- 0.5) * 10(-2) M(-1) s(-1)], and the observed equilibrium constant (K(obs) = 740 +/- 47 M(-1)) is slightly smaller than for 5. Glutathionylation showed a significant pH dependence, where rates increased with pH. Taken together, these results suggest that glutathionylation is a general reaction for Co(III) complexes related to Cbl. PMID- 22316336 TI - Treatment of chlamydial infections. AB - INTRODUCTION: Chlamydiae are obligate intracellular bacterial pathogens whose entry into mucosal epithelial cells is required for intracellular survival and subsequent growth. The life cycle of Chlamydia spp. and the ability to cause persistent, often subclinical infection, has major ramifications for diagnosis and treatment of C. trachomatis and C. pneumoniae infections in humans. AREAS COVERED: This up-to-date review describes the current state of knowledge of antimicrobial susceptibilities and treatment of genital infections due to C. trachomatis and respiratory infections due to C. pneumoniae. EXPERT OPINION: Chlamydiae are susceptible to antibiotics that interfere with DNA and protein synthesis, including tetracyclines, macrolides and quinolones, which are the compounds that have been most extensively studied and used for treatment of human infection. Treatment of individuals with C. trachomatis genital infection prevents sexual transmission and complications, including pelvic inflammatory disease. Treatment of pregnant women will prevent the transmission of infection to infants during delivery. The benefits of treatment of respiratory infections due to C. pneumoniae are more difficult to assess, primarily because of the lack of FDA-approved, specific diagnostic tests for detection of the organism in clinical samples. The majority of published studies have relied on serology for diagnosis, making it difficult to assess microbiologic efficacy. PMID- 22316337 TI - Prenatal nutrition intervention to reduce mutans streptococci among low-income women. AB - OBJECTIVES: The objective of this study is to assess the effectiveness of a prenatal nutrition intervention to reduce sugar intake and mutans streptococci (mutans) among low-income women. METHODS: Pregnant women were recruited from the obstetrics service at a community health center in Connecticut. Inclusion criteria were >=18 years of age; mutans levels >10, 000 colony forming units/ml as determined by Dentocult SM(r) kits (Orion Diagnostica Oy, Espoo, Finland); and >3 months pregnant. Women were randomized to receive education alone [education intervention (EI)] or education and a 1-hour nutrition group session at 9 months and 6 weeks postpartum [education and nutrition intervention (EIN)]. Mutans and questionnaire data were collected at baseline, 9 months, 6 weeks, and 3 months postpartum. One hundred twenty completed the baseline visit and 93 (77%) completed all four visits. Sugar intake was assessed by the Food Frequency Questionnaire and clinical information was abstracted from medical charts. RESULTS: Mean age was 26.3 years [standard deviation (SD)= 6], 73% were Hispanic, 29% had lived in the United States < 6 years; 48% completed high school; 27% were married; mean total sugar intake at baseline was 149g (SD = 85). Repeated measures analysis of variance showed that mutans levels declined significantly in both groups, but that the EI group had significantly lower mutans levels at the final assessment compared with EIN. Sugar intake also declined significantly, but there were no significant differences between groups. CONCLUSIONS: The study demonstrated the following: a) the feasibility of conducting the intervention at community health center sites among low-income pregnant women; b) the effectiveness of education to reduce mutans/sugar intake; and c) the need to improve the nutrition intervention to obtain additional gains in mutans reduction. PMID- 22316338 TI - Attitudes and knowledge about naloxone and overdose prevention among detained drug users in Ningbo, China. AB - BACKGROUND: To date there has been limited research on both the prevalence of overdose and drug user knowledge about overdose prevention and response methods in China. In addition, there has been no effort to integrate naloxone information and distribution into pre-release services for drug users detained in isolated compulsory detoxification facilities in China. METHODS: The authors conducted a survey of 279 heroin users in isolated compulsory detoxification centers in Ningbo, China in an attempt to evaluate the possibility of conducting prelease peer naloxone programs in Ningbo isolated compulsory detoxification centers. Respondents' demographic background, history of heroin overdoses, and attitudes/knowledge about overdose prevention and response were collected. RESULTS: While drug users in Ningbo's compulsory detoxification centers have limited understandings of how to effectively respond to overdoses, they expressed concern about the possibility of overdose, interest in participating in overdose prevention and response programs, and a willingness to help their peers. In general, there was no significant difference in history and attitudes/knowledge of overdose between male and female participants. CONCLUSION: Based on the findings of this research, our survey provides preliminary evidence that detained drug users have considerable interest in overdose prevention and response information and willingness to help peers. However, drug users in Ningbo isolated compulsory detoxification centers currently have limited understandings of effective ways of helping to prevent overdose deaths. PMID- 22316339 TI - Inherited platelet disorders. AB - OBJECTIVE: To present the latest information on inherited platelet disorders in domestic animals. DATA SOURCES: Research articles and reviews spanning 40 years available on PubMed. HUMAN DATA SYNTHESIS: Information regarding inherited platelet disorders in people is plentiful and often descriptions of human conditions have led to the identification of similar disorders in veterinary species. There are exceptions, however, in which specific inherited platelet disorders were first described in animals with subsequent identification in people. VETERINARY DATA SYNTHESIS: Many inherited platelet disorders have been documented in animals at the functional and molecular level and that information is presented in this review. CONCLUSIONS: Much progress has been made in the past 20 years in the characterization of inherited platelet disorders in animals at the functional, biochemical, and molecular level. The study of inherited platelet disorders has greatly enhanced the understanding of platelet physiology and has led in some instances to the development of platelet inhibitory medications. Characterization of inherited disorders at the molecular level greatly facilitates diagnosis and identification of affected and heterozygous animals thus avoiding propagation of the defect by breeders. When used with available functional and biochemical diagnostic tests, it significantly enhances the quality of care and case management. PMID- 22316340 TI - Quantitative chemical imaging with multiplex stimulated Raman scattering microscopy. AB - Stimulated Raman scattering (SRS) microscopy is a newly developed label-free chemical imaging technique that overcomes the speed limitation of confocal Raman microscopy while avoiding the nonresonant background problem of coherent anti Stokes Raman scattering (CARS) microscopy. Previous demonstrations have been limited to single Raman band measurements. We present a novel modulation multiplexing approach that allows real-time detection of multiple species using the fast Fourier transform. We demonstrate the quantitative determination of chemical concentrations in a ternary mixture. Furthermore, two imaging applications are pursued: (1) quantitative determination of oil content as well as pigment and protein concentration in microalgae cultures; and (2) 3D high resolution imaging of blood, lipids, and protein distribution in ex vivo mouse skin tissue. We believe that quantitative multiplex SRS uniquely combines the advantage of fast label-free imaging with the fingerprinting capability of Raman spectroscopy and enables numerous applications in lipid biology as well as biomedical imaging. PMID- 22316341 TI - PinX1 regulation of telomerase activity and apoptosis in nasopharyngeal carcinoma cells. AB - BACKGROUND: Human interacting protein X1 (PinX1) has been identified as a critical telomerase inhibitor and proposed to be a putative tumor suppressor gene. Loss of PinX1 has been found in a large variety of malignancies, however, its function in inhibiting telomerase activity of tumor cells is not well documented. Here we show that PinX1 is essential for down-regulation telomerase activity of nasopharyngeal carcinoma. METHODS: Expression vectors of human PinX1 (pEGFP-C3-PinX1) and its small interfering RNA (PinX1-FAM-siRNA) were constructed and transfected into NPC. Their effects on mRNA of telomerase catalytic subunit (hTERT), telomerase activity, cell proliferation, cell migration, wound healing, cell cycles and apoptosis were examined using semi-quantitative RT-PCR, stretch PCR, MTT assay, Transwell, scratch assay and flow cytometry, respectively. RESULTS: Transfection of pEGFP-C3-PinX1 and PinX1-FAM-siRNA increased and reduced PinX1 mRNA by 1.6-fold and 70%, respectively. Over-expression of PinX1 decreased hTERT mRNA by 21%, reduced telomerase activity, inhibited cell growth, migration and wound healing ability, arrested cells in G0/G1 phase, and increased apoptotic index. In contrast, down-regulation of PinX1 did not alter the above characteristics. CONCLUSIONS: PinX1 may play important roles in NPC proliferation, migration and apoptosis and has application potential in tumor targeted gene therapy. PMID- 22316343 TI - Synthesis and antitumoral evaluation of 7-chloro-4-quinolinylhydrazones derivatives. AB - A series of twenty-one 7-chloro-4-quinolinylhydrazones derivatives (3a-u) have been synthesized and evaluated for their cytotoxic potential against three cancer cell lines using MTT assay. The compounds 3b, 3e, 3f, 3h, 3j, 3n, 3r and 3u displayed more than 90% of growth inhibition (GI) and they were selected for in vitro anticancer activities evaluation against four human cancer cell lines. These results were expressed as the concentrations that induce 50% inhibition of cell growth (IC50) in MUg/mL. Considering that, compounds 3b, 3e, 3h, 3n, 3r and 3u exhibited good cytotoxic activity against at least three cancer cell lines (0.7967-4.200 MUg/mL). In general, we observed that the presence of electron withdrawing groups in the benzene ring is important for the anticancer activity in this series, such as fluorine (3h), chlorine (3b) amd bromine (3e) groups in meta position and nitro group (3r) in para position. These derivatives could be considered interesting start points to develop a new anticancer drug and confirm the potential of chloroquine derivatives as lead compounds in anticancer drug discovery. PMID- 22316344 TI - Association between prestroke disability and inpatient mortality and length of acute hospital stay after acute stroke. AB - OBJECTIVES: To examine the prognostic value of prestroke disability in predicting inpatient mortality and length of hospital stay (LOS) independent of age, sex, and stroke type and severity. DESIGN: Retrospective analysis of prospectively collected stroke registers. SETTING: United Kingdom. PARTICIPANTS: Fourteen thousand four hundred thirty-seven individuals (52.9% female, mean age 75.4 +/- 12.1) with stroke (82% ischemic) admitted to three university hospitals. MEASUREMENTS: Data were examined from three hospital registers: Aintree (2005 2010), Newcastle (2000-2005), and Norwich (1997-2010). Risk of inpatient death and prolonged hospital stay according to prestroke disability using the modified Rankin Score (mRs) were assessed using logistic regression adjusting for age, sex, and stroke subtype (ischemic vs hemorrhagic) and severity. RESULTS: Inpatient death was 20.8%. In fully adjusted models, higher prestroke mRs was associated with significantly greater risk of mortality (for mRs = 1, 2, 3, 4, and 5 vs mRs = 0: odds ratio (OR)=1.28, 95% confidence interval (CI)=1.09-1.50; OR = 1.50, 95% CI = 1.29-1.75; OR = 1.85, 95% CI = 1.60-2.13; OR = 2.56, 95% CI = 2.15-3.04; and OR = 4.48, 95% CI = 3.47-5.80, respectively). The relationship appeared to be linear, and each point increase in mRs equated to being approximately 5 years older. Although age and stroke type appear to be strong independent predictors of LOS, premorbid mRs also predicted longer LOS regardless of discharge status. The predictability of the model using these parameters was very good (receiver operating characteristic: 0.82 for death and 0.65-0.70 for LOS). CONCLUSION: Prestroke disability predicts inpatient death and LOS, independent of age, sex, and stroke type and severity. Whether this is related to mental or physical disability should be examined in future prospective studies. PMID- 22316345 TI - Co-occurrence of aflatoxins B1, B2, G1 and G2, ochratoxin A, zearalenone, deoxynivalenol, and citreoviridin in rice in Brazil. AB - A total of 230 samples of processed rice and its sub-products or derived products were analysed to establish the co-occurrence of several mycotoxins. Samples were analysed in the period 2007-2009 due to the outbreak of beriberi associated with the consumption of rice stored in inappropriate conditions in Brazil. According to data from the Ministry of Health, 323 cases of disease were registered in 2006, of which at least 47 cases resulted in death. The occurrence of total aflatoxin (AFT) (aflatoxin B(1) + B(2) + G(1) + G(2)), ochratoxin A (OTA), zearalenone (ZON), deoxynivalenol (DON), and citreoviridin (CTV) was 58.7%, 40.0%, 45.2%, 8.3% and 22.5%, respectively. From 166 rice samples analysed, 55% had levels <0.11 ug kg(-1) for AFT. For OTA and ZON, of 165 rice samples analysed, 28% and 29% were contaminated with levels from 0.20 to 0.24 ug kg(-1) and from 3.6 to 290.0 ug kg(-1), respectively. One sample (0.6%) was contaminated with 4872.0 ug kg(-1) of ZON. A total of 91% of rice samples (n = 165) did not contain detectable DON (<30.00 ug kg(-1)), although the highest level of contamination was found to be 244 ug kg(-1). From the total of 65 samples analysed, 94% had no detectable CTV (<0.9 ug kg(-1)), with a range from 0.9 to 31.1 ug kg(-1) in 6% of the samples. The highest levels of contamination were found in rice sub-products or derived products from the husk and rice bran. Co occurrence was observed for AFT and ZON in 17.0%, AFT and OTA in 24.2%, AFT and CTV in 6.2%, OTA and CTV in 4.6%, and ZON and CTV in 3.1%. These fractions were also the major contributors for the co-occurrence. The results found show the necessity of monitoring rice production. PMID- 22316346 TI - Optimum bronchodilator combinations in chronic obstructive pulmonary disease: what is the current evidence? AB - Chronic obstructive pulmonary disease (COPD) is a respiratory syndrome affecting more than 80 million people worldwide and is estimated to become the third leading cause of death worldwide by 2030. A standard-of-care approach to COPD treatment is multifaceted, including pharmacological and non-pharmacological therapies, yet the optimum combination among many bronchodilator possibilities remains unclear. We discuss the evidence for effectiveness of combination bronchodilator and inhaled corticosteroid therapy in affecting the minimal clinically important difference for these agents in COPD. We propose an approach to the rational use of these combinations that favours the combination of long acting beta-adrenergic agents with long-acting anticholinergic agents in lieu of any other bronchodilators whenever possible. We suggest that, to better detect effects of disease modification in COPD, future studies of combination bronchodilator effectiveness should emphasize endpoints other than short-term change in post-bronchodilator forced expiratory volume in 1 second (FEV(1)). PMID- 22316347 TI - Pharmacotherapy of attention-deficit hyperactivity disorder in adolescents. AB - Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioural disorder in children and adolescents, consisting of developmentally inappropriate levels of inattention and/or hyperactivity and impulsivity. The majority of children with ADHD will continue to experience significant ADHD symptoms as teens. ADHD in adolescents can result in significant functional impairment and poorer quality of life. Children and adolescents with ADHD are at higher risk of developing other psychiatric illnesses such as mood, conduct and substance abuse disorders. Stimulants (amphetamines and methylphenidates) and nonstimulants (atomoxetine, guanfacine extended-release (XR) and clonidine XR) have been found to be effective and are approved by the US FDA for the treatment of ADHD in adolescents in the US. Of the agents approved in the US, only guanfacine XR and clonidine XR are not approved in any other countries. There is growing evidence that treatment of ADHD with stimulants reduces the risk of development of other psychiatric co-morbidities, including substance abuse disorders. To date, all FDA approved stimulants and nonstimulants that have been adequately studied have been demonstrated to be safe and effective in treating ADHD in both children and adolescents. Therefore, clinical decisions used in selecting pharmacotherapy to treat ADHD in children aged 6-12 years can be applied in the adolescent population. PMID- 22316349 TI - Pharmacokinetics of intravenous ibuprofen: implications of time of infusion in the treatment of pain and fever. AB - Intravenous NSAIDs are playing an increasingly large role in analgesia, anti inflammation and antipyresis in the hospitalized setting. For many years, ketorolac was the only intravenous NSAID available in the US, but in 2009 intravenous ibuprofen was approved by the US FDA for the treatment of pain and fever in adults. In developing intravenous ibuprofen, a range of times of infusion and dosing levels have been utilized and compared with the oral route of administration. The earliest studies utilized a 60-minute infusion, and later a 30-minute infusion was used for the pivotal/registration studies demonstrating efficacy and safety. Another recent trial in healthy volunteers demonstrated a safe and tolerable rapid infusion (5-7 minute) of intravenous ibuprofen. The pharmacokinetic data from all of the clinical trials on 400 and 800 mg doses of intravenous ibuprofen were compiled, and pharmacokinetic modelling was utilized to simulate any data not acquired in the clinical studies. The pharmacokinetic profile of the following doses was modelled: 30-minute infusion of 800 mg intravenous ibuprofen, 5- to 7-minute infusion of 400 mg intravenous ibuprofen and 400 mg ibuprofen oral tablet. These pharmacokinetic analyses revealed that, in general, maximum plasma concentration (C(max)) decreases considerably as the length of the infusion increases and that an oral dose is not able to achieve the C(max) level of any intravenous dose. For the rapid infusion, C(max) was twice that of the oral dose and, as expected, time to C(max) (t(max)) was much more rapid than with the oral dose. However, the oral dose still maintained virtually 100% oral bioavailability. The efficacy of intravenous ibuprofen in terms of pain and fever has also been studied and this review found the drug to be efficacious for both indications. Future areas of study should include assessment of the analgesic and antipyretic efficacy of a rapid (5- to 10-minute) infusion and further assessment of pre-emptive administration of intravenous ibuprofen as part of a multimodal analgesic approach in the surgical setting. PMID- 22316350 TI - Antibacterials as adjuncts to incision and drainage for adults with purulent methicillin-resistant Staphylococcus aureus (MRSA) skin infections. AB - The annual incidence of skin and soft tissue infections (SSTIs) has nearly tripled in the US since the early 1990s. Many purulent SSTIs in the community setting are caused by methicillin-resistant Staphylococcus aureus (MRSA). Incision and drainage (I&D) are indicated for most purulent MRSA infections; however, the use of adjunctive antibacterials is controversial. The objective of this study was to systematically evaluate studies that have investigated whether or not antibacterials provide added benefit to I&D alone for purulent MRSA SSTIs. We included articles from MEDLINE and The Cochrane Library that fulfilled the following criteria: (i) original research; (ii) English language; (iii) compared I&D alone versus I&D plus antibacterials for purulent MRSA SSTIs; and (iv) compared patient outcomes. We also reviewed the references of these articles to identify other relevant studies. Studies that solely examined paediatric patients were excluded. To facilitate cross-study comparison, we systematically evaluated the following study characteristics: (i) study design; (ii) patient population; (iii) comparator groups; (iv) sample size; (v) outcome measures; (vi) outcome definitions; (vii) duration of follow-up; and (viii) measurement and adjustment of potential confounding variables. Eleven studies, spanning more than 30 years, met inclusion criteria. Two of these were conducted prior to the emergence of MRSA in the community; another evaluated cephalexin versus placebo for MRSA. None of these found added benefit of adjunctive antibacterials. Four studies compared health outcomes between patients who received 'active' or 'appropriate' therapy and those who received 'inactive' or 'inappropriate' therapy after I&D for purulent MRSA SSTIs. Two of these studies found 'active' or 'appropriate' therapy to be beneficial, while two others did not. Four studies compared health outcomes between patients who received anti-MRSA antibacterials plus I&D with those who received alternative antibacterials plus I&D for purulent MRSA SSTIs. Three of these reported improved outcomes with anti-MRSA antibacterials, while another reported mixed findings. Presently, the bulk of the available evidence suggests anti-MRSA antibacterials provide added benefit to I&D alone for purulent MRSA SSTIs; however, the current evidence is limited to small, case-control, observational studies. PMID- 22316351 TI - Pertuzumab: in the first-line treatment of HER2-positive metastatic breast cancer. AB - The humanized monoclonal antibody pertuzumab is the first in a new class of drugs, the human epidermal growth factor receptor (HER) dimerization inhibitors. Given that pertuzumab binds to a different epitope of the HER2 extracellular domain than trastuzumab, combination therapy with pertuzumab plus trastuzumab may result in more comprehensive blockade of HER2 signalling than can be achieved with trastuzumab alone. The efficacy of adding pertuzumab to trastuzumab plus docetaxel for the first-line treatment of HER2-positive metastatic breast cancer was demonstrated in the randomized, double-blind, multinational, phase III CLEOPATRA trial. Both independently assessed progression-free survival (primary endpoint) and investigator-assessed progression-free survival were significantly improved in patients receiving pertuzumab plus trastuzumab and docetaxel compared with those receiving placebo plus trastuzumab and docetaxel. The prespecified interim analysis of survival revealed a strong trend towards a survival benefit associated with pertuzumab, although this was not considered statistically significant. The objective response rate was higher with pertuzumab than with placebo. Intravenous pertuzumab had an acceptable tolerability profile when added to trastuzumab and docetaxel in the CLEOPATRA trial. PMID- 22316352 TI - Azithromycin 1.5% ophthalmic solution: in purulent bacterial or trachomatous conjunctivitis. AB - The second-generation macrolide azithromycin is available as a 1.5% ophthalmic solution for use in the treatment of bacterial or trachomatous conjunctivitis. This article reviews the pharmacological properties of azithromycin 1.5% ophthalmic solution and its clinical efficacy and tolerability in patients with purulent bacterial conjunctivitis or trachomatous conjunctivitis caused by Chlamydia trachomatis. Azithromycin 1.5% ophthalmic solution had good in vitro activity against Haemophilus influenzae and C. trachomatis, and achieved good concentrations in tear samples from healthy volunteers. Azithromycin 1.5% ophthalmic solution for 3 days (1 drop twice daily) was noninferior to tobramycin 0.3% ophthalmic solution for 7 days (1 drop every 2 hours) in paediatric and adult patients with purulent bacterial conjunctivitis, with regard to clinical cure and bacteriological resolution on day 9, in a randomized, investigator masked, multicentre study. In children with trachomatous inflammation, 3-day treatment with azithromycin 1.5% ophthalmic solution was noninferior to a single dose of azithromycin oral suspension, with regard to clinical cure rate in the worst eye at 60 days, in a randomized, double-masked, multicentre study. Azithromycin 1.5% ophthalmic solution was well tolerated in patients with bacterial or trachomatous conjunctivitis. Most events were of mild to moderate severity. PMID- 22316353 TI - Tapentadol extended release: in adults with chronic pain. AB - The extended release (ER; as ascribed in the US) or prolonged release (PR; as ascribed in Europe) formulation (hereafter referred to as ER) of the oral analgesic tapentadol is believed to exert its analgesic effects via MU-opioid receptor agonistic and norepinephrine reuptake inhibitory activity. Direct conversion between tapentadol immediate release and tapentadol ER is permissible utilizing approximately equivalent total daily doses. For the most part, shorter term (15 weeks) therapy with tapentadol ER 100-250 mg twice daily provided more effective pain relief and significantly improved functional and health status outcomes compared with placebo in four well designed studies in adult patients with moderate to severe chronic pain associated with knee osteoarthritis, the lower back or diabetic neuropathy. Moreover, longer-term (<=24 months) therapy with tapentadol ER provided sustained analgesic effects in two multinational tolerability studies in patients with moderate to severe chronic pain associated with knee or hip osteoarthritis or the lower back. The development of tolerance was not observed in clinical studies of tapentadol ER, with the mean total daily dose and the analgesic (mean pain intensity) scores remaining relatively stable over <=24 months' therapy. Oral tapentadol ER therapy for up to 24 months was generally well tolerated, with the nature of treatment-emergent adverse events generally similar across the clinical studies. PMID- 22316354 TI - Budesonide/formoterol Turbuhaler(r): a review of its use in chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) is a highly heterogeneous, progressive inflammatory disease that imposes considerable economic and healthcare burdens on society, with the disease predicted to remain a leading cause of morbidity and mortality worldwide in the future. Current pharmacological treatment can improve symptoms of the disease, but not progression. Global Initiative for Chronic Obstructive Lung Disease guidelines recommend that patients with moderate COPD should use one or more long-acting bronchodilators (e.g. a long-acting beta(2)-agonist) as required and, for those with severe and very severe disease who are experiencing repeated COPD exacerbations, an inhaled corticosteroid should be added as required. Budesonide/formoterol Turbuhaler(r) (Symbicort(r) Turbuhaler(r)) is a dry powder inhaler (DPI) that combines these two classes of drugs in a single inhaler, thereby making administration easier and more convenient. Budesonide/formoterol Turbuhaler(r) (delivered dose 320 MUg/9 MUg) is recommended for the symptomatic treatment of adult patients with severe COPD (forced expiratory volume in 1 second <50% of predicted value) and a history of repeated exacerbations, who have significant symptoms despite regular therapy with long-acting bronchodilators. This article reviews the pharmacological properties and clinical use of budesonide/formoterol Turbuhaler(r) in adult patients with moderate to severe COPD. Budesonide/formoterol Turbuhaler(r) (320 MUg/9 MUg twice daily) was effective and well tolerated in adult patients with moderate to severe COPD participating in large, multicentre trials of up to 12 months' duration. Budesonide/formoterol Turbuhaler(r) improved lung function, exacerbation rates, COPD symptom scores and health status from baseline to a significantly greater extent than placebo and, in general, than the individual monotherapies in these trials. Moreover, as reflected in the faster onset of action of formoterol than salmeterol, budesonide/formoterol Turbuhaler(r) was more effective than salmeterol/fluticasone propionate DPI at improving the patient's ability to perform morning activities in a short-term study. In the 12-week CLIMB trial, adding budesonide/formoterol Turbuhaler(r) to inhaled tiotropium bromide therapy was significantly more effective than adding placebo to tiotropium bromide therapy. Thus, inhaled budesonide/formoterol, either alone or as add-on therapy to other medications, continues to be a useful option for the management of COPD. PMID- 22316355 TI - Romiplostim: a review of its use in immune thrombocytopenia. AB - Romiplostim (Nplate(r)) is an Fc-peptide fusion protein (peptibody) that acts as a thrombopoietin receptor agonist; it has no amino acid sequence homology with endogenous thrombopoietin. This article reviews the clinical efficacy and tolerability of subcutaneous romiplostim in adults with immune thrombocytopenia (ITP), as well as summarizing its pharmacological properties. The efficacy of 12 or 24 weeks' therapy with subcutaneous romiplostim was compared with that of placebo in patients with ITP in three randomized, double-blind, multicentre, phase III trials. In the two 24-week trials, the durable platelet response rate (primary endpoint) was significantly higher with romiplostim than with placebo in both splenectomized and nonsplenectomized patients. In addition, the majority of romiplostim recipients were able to discontinue or reduce their concurrent ITP therapy, and romiplostim improved health-related quality of life (HR-QOL). In the 12-week trial in splenectomized or nonsplenectomized Japanese patients with ITP, the median number of weeks with a platelet response (primary endpoint) was significantly higher with romiplostim than with placebo. Two extension studies (with median durations of romiplostim treatment of 78 and 100 weeks) demonstrated that long-term therapy with romiplostim maintained platelet counts in the target range in patients with ITP. In a randomized, open-label, multicentre, 52-week, phase IIIb trial, romiplostim was more effective than the medical standard of care in nonsplenectomized patients with ITP who had received at least one prior ITP treatment. Significantly fewer patients receiving romiplostim versus the medical standard of care experienced treatment failure or required splenectomy (co-primary endpoints), and clinically meaningful improvements from baseline in HR-QOL scores were seen with romiplostim. Subcutaneous romiplostim was generally well tolerated in patients with ITP; in short-term trials, the majority of adverse events were of mild to moderate severity and appeared to be related to the underlying thrombocytopenia. The incidence of bleeding events of at least grade 3 severity did not significantly differ between romiplostim and placebo recipients, and was significantly lower with romiplostim than with the medical standard of care. Romiplostim did not appear to be associated with an increased risk of haematological malignancies or an increased risk of thrombotic events. Although binding antibodies against romiplostim or thrombopoietin developed in some romiplostim recipients, with neutralizing antibodies to romiplostim detected in two romiplostim recipients, antibodies cross reacting to thrombopoietin have not been detected. Romiplostim was associated with modest increases in bone marrow reticulin in some patients with ITP; reductions in reticulin were usually seen when romiplostim was discontinued. In conclusion, subcutaneous romiplostim is a valuable agent for use in patients with refractory chronic ITP. PMID- 22316356 TI - Post renal transplantation Kaposi's sarcoma: a review of its epidemiology, pathogenesis, diagnosis, clinical aspects, and therapy. AB - BACKGROUND: Kaposi's sarcoma (KS) is a vascular malignancy primarily involving the skin. This neoplasm occurs commonly in acquired immunodeficiency syndrome (AIDS) and post solid organ transplantation. Human herpesvirus type 8 (HHV-8) has been shown to play a causative role in AIDS-associated KS and in post renal transplantation KS. METHODS: Based on a MEDLINE search, we present a review of the current information on the epidemiology, pathogenesis, diagnosis and treatment of post-transplantation KS (PT-KS) with an emphasis on renal transplantation. RESULT: The different frequencies of PT-KS in different parts of the world seem to be related to seroprevalence of HHV-8 infection. Following renal transplantation and the administration of immunosuppressive therapy, HHV-8 may reactivate. The renal tubular epithelium is a site for HHV-8 latency. Rates of PT-KS in seropositive recipients and anti-HHV-8 mismatched recipients (donor+/recipient-) are approximately 13% and 4.6%, respectively. Additional risk factors for the development of PT-KS include skin color, country of birth, age at the time of transplantation, and different induction regimens including anti thymocyte globulin, steroid, or anti-interleukin 2-receptor antagonists. Skin is the major site of involvement. Surprisingly, involvement of the transplanted organ has been reported to be extremely rare. Reduction in immunosuppressive therapy and switching to mammalian targets of rapamycin inhibitors, such as sirolimus, are effective treatments for PT-KS. In patients with no response to reduction in immunosuppressive therapy, systemic chemotherapy with different regimens has been reported to be successful. CONCLUSION: PT-KS in renal transplant patients is an important problem specifically in southern Europe and the Middle East. In the majority of patients, the diagnosis based on clinical suspicion is always essential. Clinicians should bear in mind that PT-KS may threaten graft function and hence result in rejection complications. Appropriate management increases patient survival. PMID- 22316357 TI - The effects of a 25% discount on fruits and vegetables: results of a randomized trial in a three-dimensional web-based supermarket. AB - BACKGROUND: Lowering the price of fruit and vegetables is a promising strategy in stimulating the purchase of those foods. However, the true effects of this strategy are not well studied and it is unclear how the money saved is spent. The aim of this study is to examine the effects of a 25% discount on fruits and vegetables on food purchases in a supermarket environment. METHODS: A randomized controlled trial with two research conditions was conducted: a control condition with regular prices (n = 52) and an experimental condition with a 25% discount on fruits and vegetables (n = 63). The experiment was carried out using a three dimensional web-based supermarket, which is a software application in the image of a real supermarket. Data were collected in 2010 in the Netherlands. Participants received a fixed budget and were asked to buy weekly household groceries at the web-based supermarket. Differences in fruit and vegetable purchases, differences in expenditures in other food categories and differences in total calories were analyzed using independent samples t-tests and multiple linear regression models accounting for potential effect modifiers and confounders. RESULTS: The purchased amount of fruit plus vegetables was significantly higher in the experimental condition compared to the control condition (Delta984 g per household per week, p = .03) after appropriate adjustments. This corresponds to a 25% difference compared to the control group. Both groups had similar expenditures in unhealthier food categories, including desserts, soda, crisps, candy and chocolate. Furthermore, both groups purchased an equal number of food items and an equal amount of calories, indicating that participants in the discount condition did not spend the money they saved from the discounts on other foods than fruits and vegetables. CONCLUSION: A 25% discount on fruits and vegetables was effective in stimulating purchases of those products and did neither lead to higher expenditures in unhealthier food categories nor to higher total calories purchased. Future studies in real supermarkets need to confirm these findings. PMID- 22316358 TI - Colonization of Vitis spp. wood by sGFP-transformed Phaeomoniella chlamydospora, a tracheomycotic fungus involved in Esca disease. AB - To evaluate wood colonization and interactions with Vitis spp. of Phaeomoniella chlamydospora, a fungal agent involved in Esca disease, isolate CBS 229.95 was transformed using a pCT74 construct which contained the genetic markers for synthetic green fluorescent protein (sGFP) and hygromycin B phosphotransferase. Nine stable P. chlamydospora fungal transformants (Pch-sGFP lines) were obtained using polyethylene-glycol-mediated transformation of protoplasts. These were characterized for sgfp and hygromycin B phosphotransferase (hph) genome insertions and for sGFP fluorescence emission, using quantitative polymerase chain reaction and fluorimetric systems, respectively. No correlation was observed between sgfp copy number genome insertion and sGFP fluorescence expression. Cuttings of Vitis vinifera 'Montepulciano', 'Verdicchio', 'Sangiovese', 'Biancame', and 'Cabernet Sauvignon'; and the grapevine rootstocks 'Kober 5BB', 'SO4', '420A', '1103P', and V. rupestris were inoculated by immersion in a conidial suspension of the selected fungal Pch-sGFP71 line and incubated at 4 +/- 1 and 25 +/- 1 degrees C. Wood colonization was estimated through epifluorescence microscopy and was affected by incubation temperature. After 6 months at 4 +/- 1 degrees C, the fungal growth was completely inhibited. At 25 +/- 1 degrees C, the highest extent of wood colonization was recorded in Montepulciano and Verdicchio, with the lowest in the rootstocks SO4 and V. rupestris. The expression of the Pch-sGFP71 transformed line was localized in the xylem area, primarily around the vessels. The use of sGFP-transformed P. chlamydospora helped to clarify different aspects associated with the location of this pathogen in grapevine tissue, before disease symptom expression. PMID- 22316359 TI - Near field guided chemical nanopatterning. AB - This article demonstrates the possibility of creating well-defined and functional surface chemical nanopatterns using the optical near field of metal nanostructures and a photosensitive organic layer. The intensity distribution of the near field controlled the site and the extent of the photochemical reaction at the surface. The resulting pattern was used to guide the controlled assembly of colloids with a complementary surface functionality onto the substrate. Gold colloids of 20 nm diameter were covalently bound to the activated nanosites and proved the functionality of the suboptical wavelength structures and enabled direct visualization by means of electron microscopy. Our results prove, for the first time, the possibility of using optical near field to perform chemical reactions and assembly at the nanoscale. PMID- 22316360 TI - The evolution of antiandrogens: MDV3100 comes of age. PMID- 22316362 TI - Fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting. AB - For patients receiving cancer chemotherapy, the ongoing development of antiemetic treatment is of significant importance. Patients consider nausea and vomiting among the most distressing symptoms of chemotherapy, and as new antiemetics have been very successful in prevention of vomiting, agents effective against nausea have become one of the major unmet needs. The neurokinin (NK)(1) receptor antagonist aprepitant potentiates the antiemetic efficacy of the combination of a serotonin receptor antagonist and a corticosteroid. Fosaprepitant (intravenous prodrug of aprepitant) given as a single intravenous dose of 150 mg can replace the aprepitant 3-day oral regimen. This article focuses on the development and clinical application of fosaprepitant. PMID- 22316363 TI - Crizotinib: a drug that crystallizes a unique molecular subset of non-small-cell lung cancer. AB - Crizotinib (Pfizer, CA, USA) is an oral small-molecule RTK inhibitor that targets ALK and MET, and potentially other RTKs. Crizotinib was approved by the US FDA on 26 August 2011 for the treatment of ALK-rearranged non-small-cell lung cancer (NSCLC), as detected by ALK break-apart FISH assay. This conditional approval was based on response rates of 50-61% from 255 ALK-rearranged NSCLC patients enrolled in two ongoing single-arm crizotinib trials. Side effects of crizotinib mostly consist of grade 1-2 gastrointestinal events (nausea, vomiting, diarrhea and constipation), grade 1-2 edema and fatigue, grade 1 visual disorders, rare cases of elevated liver enzymes and pneumonitis (1.6%). Confirmatory trials comparing crizotinib to standard chemotherapy in upfront (ClinicalTrials.gov identifier: NCT01154140) and salvage (ClinicalTrials.gov identifier: NCT00932451) treatment settings of ALK-rearranged NSCLC are ongoing. It took an unprecedented rapid 4 years from the publication of the discovery of ALK-rearranged NSCLC in August 2007 to the conditional approval of crizotinib in August 2011. PMID- 22316364 TI - Cetuximab in non-small-cell lung cancer. AB - Cetuximab is a chimeric human-mouse anti-EGF receptor monoclonal antibody. In Phase I studies, no dose-limiting toxicities were observed with cetuximab as a single agent or combined with chemotherapy; pharmacokinetic and pharmacodynamic analyses supported 250 mg/m(2) weekly administration. Skin toxicity, diarrhea and fatigue were the most common toxicities. The positive results obtained in Phase II trials in patients with advanced non-small-cell lung cancer prompted two randomized Phase III trials evaluating cetuximab in addition to first-line chemotherapy. Both trials showed a small benefit in overall survival for the experimental treatment, which was considered insufficient by the EMA for marketing approval. However, a subgroup analysis of the FLEX Phase III trial recently demonstrated a larger survival benefit from the experimental treatment in patients with high immunohistochemical EGF receptor expression. This finding, if confirmed prospectively, could represent a new opportunity for positioning cetuximab into the standard treatment of advanced non-small-cell lung carcinoma. PMID- 22316365 TI - Therapeutic potential of irreversible electroporation in sarcoma. AB - Irreversible electroporation is a newly developed nonthermal tissue ablation technique in which certain short-duration electrical fields are used to permanently permeabilize the cell membrane to disrupt cellular homeostasis. This disruption of cellular homeostasis initiates apoptosis, which leads to permanent cell death. Sarcomas are generally divided into soft-tissue and bone sarcomas based on their different mesenchymal origins and anatomical locations. Each of these sarcomas present in different ways, exhibit different behaviors and prognoses, and present unique therapeutic challenges. In this article, a series of recently conducted irreversible electroporation treatment for sarcomas based on local nonthermal ablation are summarized, and the therapeutic potential of this newly developed technique is assessed. PMID- 22316366 TI - Minimizing toxicity in early-stage testicular cancer treatment. AB - Testicular cancer is the paradigm of a curable malignancy, with 10-year survival rates exceeding 95%. Cisplatin-based regimes offer a survival gain of several decades of life; however, measures of outcomes in testicular cancer are evolving. Survivorship issues are becoming increasingly important in this young adult population. Long-term risks of second malignancy and cardiovascular disease secondary to chemotherapy and radiotherapy have been extensively documented, leading to an increased uptake of surveillance. However, the optimal surveillance schedule is not universally agreed upon. Research into modalities to detect relapse and frequency is ongoing. Reducing the treatment burden with fewer cycles of chemotherapy (one cycle of bleomycin, cisplatin and etoposide instead of two for stage I high-risk nonseminomatous tumors) or less toxic alternatives (carboplatin instead of radiotherapy for stage I seminomas) is currently being explored. This article details the toxicities associated with the diagnosis and treatments of early-stage testicular cancer and current strategies used to minimize toxicity while retaining the excellent cure rates. PMID- 22316367 TI - What is the best choice of partner chemotherapy with trastuzumab for metastatic breast cancer? AB - The HER2 gene and its role in pathogenicity in human breast cancer were detected in the 1980s. Trastuzumab is a monoclonal antibody directed against the HER2 membrane receptor. The aim of this article is to describe chemotherapy trastuzumab combinations that have been evaluated in patients with HER2-positive metastatic breast cancer, and to define the possible standards and options. PMID- 22316368 TI - Prognostic value of circulating tumor cells in primary and metastatic breast cancer. AB - In patients with breast cancer, there is evidence correlating the presence of circulating tumor cells (CTCs) with disease-free survival, progression-free survival and overall survival. The detection of CTCs may be useful in gaining a better understanding of the mechanisms of tumor growth and in the improvement of patient management. This review analyzes the prognostic and predictive relevance of CTCs through the principal published studies, cytometric techniques and nucleic acid-based approaches to detect CTCs, phenotypic expression of specific receptors, molecular pathways and genetic signatures for potential tailored therapies. PMID- 22316369 TI - Benign and malignant apocrine lesions of the breast. AB - Apocrine differentiation occurs in a variety of breast lesions, both benign and malignant. This review is a reflection of our critical view of the recent advances towards the understanding of this particular type of breast lesions. Focus is given to the histological criteria that allow their reproductive identification, with additional attention to the recent microarray studies. These describe the recent molecular classification of breast cancer and identify an apocrine molecular subtype that opens the door for new putative therapies for this particular type of tumor. Indeed we anticipate that the determination of androgen receptor will enter into the routine assessment of breast cancer cases and become a surrogate marker for treatment in apocrine triple-negative breast cancer. PMID- 22316370 TI - Breast cancer chemoprevention. AB - According to the National Cancer Institute Surveillance Epidemiology and End Results Cancer Statistics Review, the incidence of invasive breast cancer in the USA is 124 women per 100,000 population. Women at increased risk for breast cancer have three major options to reduce their risk, specifically screening, chemoprevention and prophylactic surgery. In this article, we focus on chemoprevention. There are three chemoprevention agents available to reduce breast cancer risk: tamoxifen, raloxifene and exemestane. In this article, we summarize the major randomized clinical trials investigating the use of these agents in the chemoprevention setting. Randomized controlled trials have shown that these agents can reduce breast cancer incidence, but the potential risks of these agents and their impact on quality of life should also be carefully considered. Indeed, it is always important to keep in mind that chemoprevention targets asymptomatic women, and therefore the decision to embark on this strategy should never be taken lightly. PMID- 22316371 TI - Progress of oncolytic viruses in sarcomas. AB - Oncolytic virotherapy has shown exciting promise for the treatment of many types of solid tumors. Pediatric sarcomas are an aggressive type of pediatric malignancy known to show limited responsiveness to current therapies, leading to unacceptably high morbidity and mortality. Oncolytic viruses have only recently been used for the treatment of this challenging cancer, and results have been encouraging. Five clinical trials are currently open evaluating the use of oncolytic viruses in pediatric malignancies. Advances in genetic engineering of the viruses include improving the ability of the virus to infect tumor cells, engineering the virus with transgenes which improve the virus' ability to kill tumor cells and manipulating the virus to enhance concomitantly administered therapies. Further understanding of the antiviral immune response and a viral induced anti-tumor immune response will permit a maximization of oncolytic virotherapy. PMID- 22316372 TI - The challenge of access to care for soft tissue sarcomas bridging pediatric and adult age: the Italian pediatric oncology view. AB - Synovial sarcoma and rhabdomyosarcoma are two high-grade soft tissue sarcoma subtypes that occur in adolescents and young adults. Managing these malignancies in patients in this age bracket poses various clinical problems, partly because different therapeutic approaches are sometimes adopted by pediatric and adult oncologists, even though they are dealing with the same condition. In this review, the doubts concerning how best to manage soft tissue sarcomas in patients between pediatric and adult ages lead up to a more general discussion of the issue of access to optimal cancer services for adolescents and young adults - a subset of patients acknowledged as being under-represented in clinical trials on therapies that may improve their outcome. The situation in Italy is described, along with action taken in an effort to bridge the gap and implement specific programs tailored to these patients. PMID- 22316373 TI - Review of recent studies on interventions for cognitive deficits in patients with cancer. AB - Research has demonstrated that patients with cancer experience cognitive deficits, often due to aggressive anticancer treatments. In this article, we critically review the interventional studies that have been conducted to investigate beneficial effects on cognitive function in cancer patients. Pharmacological agents that have been studied include psychostimulants, such as methylphenidate and modafinil, erythropoietin, and hormonal (supplement) treatments for patients who receive hormonal suppression therapy. In addition, several cognitive rehabilitation programs have been evaluated in cancer patients. Recently, the approach of physical exercise to treat cognitive deficits has received great interest, and findings from novel studies are keenly anticipated. Although, in general, the studies reviewed were well designed, future studies may wish to include larger sample sizes and pay more attention to the accurate assessment of cognitive function. PMID- 22316374 TI - Molecular mechanisms of cisplatin resistance in bladder cancer. AB - Metastatic disease is the most common mechanism of death in patients with advanced bladder cancer. As for most solid tumors, chemotherapy remains the only realistic option for palliating or curing metastatic disease. However, bladder cancer is characterized by chemoresistance. Only modest response rates are obtained using multiagent regimens including cisplatin. These low response rates and the toxicity of these regimens limit their use to patients at highest risk. Here, we review the molecular mechanisms of cisplatin resistance. These include methods to reduce cisplatin bioavailability within a cell, and defects in the machinery that produces cell death following cisplatin-induced DNA damage. While overcoming these mechanisms is a potential therapeutic approach that can increase response rates, in the short term this knowledge could be used to predict response in individual tumors. PMID- 22316375 TI - Circulating microRNAs in cancer: diagnostic and prognostic significance. AB - The involvement of microRNAs (miRs) in numerous pathological conditions is well established. In many kinds of cancer cells and animal models, various miRs have been shown to act as oncogenes or tumor suppressors. Recently, it was found that circulating miRs can be detected, and may be associated, with the clinicopathological features and prognosis of cancers, thus, providing potential novel diagnostic and prognostic markers for malignancies in humans. This review aims to address these issues based on recently published literature. PMID- 22316377 TI - A large, population-based study of age-related associations between vaginal pH and human papillomavirus infection. AB - BACKGROUND: Vaginal pH is related to genital tract inflammation and changes in the bacterial flora, both suggested cofactors for persistence of human papillomavirus (HPV) infection. To evaluate the relationship between vaginal pH and HPV, we analyzed data from our large population-based study in Guanacaste, Costa Rica. We examined vaginal pH and the risk of HPV infection, cytological abnormalities, and C. trachomatis infection. METHODS: Our study included 9,165 women aged 18-97 at enrollment with a total of 28,915 visits (mean length of follow-up = 3.4 years). Generalized estimating equations were used to evaluate the relationship between vaginal pH and HPV infection (both overall and single versus multiple types) and low-grade squamous intraepithelial lesions (LSIL), the cytomorphic manifestation of HPV infection. The relationship between enrollment vaginal pH and C. trachomatis infection was assessed by logistic regression. Results were stratified by age at visit. RESULTS: Detection of HPV was positively associated with vaginal pH, mainly in women < 35 years (p-trend = 0.009 and 0.007 for women aged < 25 and 25-34 years, respectively). Elevated vaginal pH was associated with 30% greater risk of infection with multiple HPV types and with LSIL, predominantly in women younger than 35 and 65+ years of age. Detection of C. trachomatis DNA was associated with increased vaginal pH in women < 25 years (OR 2.2 95% CI 1.0-5.0). CONCLUSIONS: Our findings suggest a possible association of the cervical microenvironment as a modifier of HPV natural history in the development of cervical precancer and cancer. Future research should include studies of vaginal pH in a more complex assessment of hormonal changes and the cervicovaginal microbiome as they relate to the natural history of cervical neoplasia. PMID- 22316378 TI - Factors affecting children's oral health: perceptions among Latino parents. AB - OBJECTIVE: The objective of this study is to understand factors that influence the oral health-related behaviors of Latino children, as reported by their parents. METHODS: Focus groups and in-depth interviews assessed parental perceptions, experiences, attributions, and beliefs regarding their children's oral health. Guiding questions focused on a) the participant's child dental experiences; b) the impact of dental problems on the child's daily activities, emotions, self-esteem; c) parental experiences coping with child's dental problems; and d) hygienic and dietary habits. Participants were purposively sampled from dental clinics and public schools with a high concentration of Latinos; 92 urban low-income Latino Spanish-speaking parents participated. Transcriptions of the audio files were thematically analyzed using a grounded theory approach. RESULTS: Parents' explanations of their children's dental experiences were categorized under the following themes: caries and diet, access to dental care, migration experiences, and routines. CONCLUSIONS: Findings revealed fundamental multilevel (i.e., individual/child, family, and community) factors that are important to consider for future interventions to reduce oral health disparities: behaviors leading to caries, parental knowledge about optimal oral health, access to sugary foods within the living environment and to fluoridated water as well as barriers to oral health care such as lack of health insurance or limited health insurance coverage, among others. PMID- 22316379 TI - Axial functionalization of sterically hindered titanium phthalocyanines. AB - Several axially functionalized, weakly aggregating titanium phthalocyanines (Pc) have been synthesized and characterized. Soluble titanium dichlorido tetrakis (1,1,4,4-tetramethyl-6,7-tetralino)-porphyrazine [Pc(#)TiCl(2)] (5) has been prepared by reductive cyclotetramerization of the respective dinitrile precursor in the presence of TiCl(4). 5 and the analogous oxido compound [Pc(#)TiO] (1) are versatile starting materials for the formation of other axially functionalized titanium phthalocyanines such as organoimido (6, 7), alkoxido and aryloxido (8, 9), peroxido (10), sulfido (12), disulfido (11), selenido (14) or diselenido (13) species. Furthermore the deprotonated ligand salts [Pc(#)M(2)] (M = Li (2), Na (3), K (4) are described. The reactivity of the titanium compounds was studied in atom group transfer reactions and ethene polymerization. The crystal structures of 5 and the free ligand Pc(#)H(2) are reported. 5 crystallizes from dichloromethane in the cubic space group Im3. The two chlorido ligands exhibit a cis arrangement. The free ligand Pc(#)H(2) crystallizes in the trigonal space group R3. PMID- 22316380 TI - Surface-dominated conduction in a 6 nm thick Bi2Se3 thin film. AB - We report a direct observation of surface dominated conduction in an intrinsic Bi(2)Se(3) thin film with a thickness of six quintuple layers grown on lattice matched CdS (0001) substrates by molecular beam epitaxy. Shubnikov-de Haas oscillations from the topological surface states suggest that the Fermi level falls inside the bulk band gap and is 53 +/- 5 meV above the Dirac point, which is in agreement with 70 +/- 20 meV obtained from scanning tunneling spectroscopies. Our results demonstrate a great potential of producing genuine topological insulator devices using Dirac Fermions of the surface states, when the film thickness is pushed to nanometer range. PMID- 22316381 TI - Assessment of shoulder position variation and its impact on IMRT and VMAT doses for head and neck cancer. AB - BACKGROUND: For radiotherapy of the head and neck, 5-point mask immobilization is used to stabilize the shoulders. Still, the daily position of the shoulders during treatment may be different from the position in the treatment plan despite correct isocenter setup. The purpose of this study was to determine the interfractional displacement of the shoulders relative to isocenter over the course of treatment and the associated dosimetric effect of this displacement. METHODS: The extent of shoulder displacements relative to isocenter was assessed for 10 patients in 5-point thermoplastic masks using image registration and daily CT-on-rails scans. Dosimetric effects on IMRT and VMAT plans were evaluated in Pinnacle based on simulation CTs modified to represent shoulder shifts between 3 and 15 mm in the superior-inferior, anterior-posterior, and right-left directions. The impact of clinically observed shoulder shifts on the low-neck dose distributions was examined. RESULTS: Shoulder motion was 2-5 mm in each direction on average but reached 20 mm. Superior shifts resulted in coverage loss, whereas inferior shifts increased the dose to the brachial plexus. These findings were generally consistent for both IMRT and VMAT plans. Over a course of observed shifts, the dose to 99% of the CTV decreased by up to 101 cGy, and the brachial plexus dose increased by up to 72 cGy. CONCLUSIONS: he position of the shoulder affects target coverage and critical structure dose, and may therefore be a concern during the setup of head and neck patients, particularly those with low neck primary disease. PMID- 22316385 TI - Enhancing visible light photo-oxidation of water with TiO2 nanowire arrays via cotreatment with H2 and NH3: synergistic effects between Ti3+ and N. AB - We report a synergistic effect involving hydrogenation and nitridation cotreatment of TiO(2) nanowire (NW) arrays that improves the water photo oxidation performance under visible light illumination. The visible light (>420 nm) photocurrent of the cotreated TiO(2) is 0.16 mA/cm(2) and accounts for 41% of the total photocurrent under simulated AM 1.5 G illumination. Electron paramagnetic resonance (EPR) spectroscopy reveals that the concentration of Ti(3+) species in the bulk of the TiO(2) following hydrogenation and nitridation cotreatment is significantly higher than that of the sample treated solely with ammonia. It is believed that the interaction between the N-dopant and Ti(3+) is the key to the extension of the active spectrum and the superior visible light water photo-oxidation activity of the hydrogenation and nitridation cotreated TiO(2) NW arrays. PMID- 22316383 TI - A physicochemical descriptor-based scoring scheme for effective and rapid filtering of kinase-like chemical space. AB - BACKGROUND: The current chemical space of known small molecules is estimated to exceed 1060 structures. Though the largest physical compound repositories contain only a few tens of millions of unique compounds, virtual screening of databases of this size is still difficult. In recent years, the application of physicochemical descriptor-based profiling, such as Lipinski's rule-of-five for drug-likeness and Oprea's criteria of lead-likeness, as early stage filters in drug discovery has gained widespread acceptance. In the current study, we outline a kinase-likeness scoring function based on known kinase inhibitors. RESULTS: The method employs a collection of 22,615 known kinase inhibitors from the ChEMBL database. A kinase-likeness score is computed using statistical analysis of nine key physicochemical descriptors for these inhibitors. Based on this score, the kinase-likeness of four publicly and commercially available databases, i.e., National Cancer Institute database (NCI), the Natural Products database (NPD), the National Institute of Health's Molecular Libraries Small Molecule Repository (MLSMR), and the World Drug Index (WDI) database, is analyzed. Three of these databases, i.e., NCI, NPD, and MLSMR are frequently used in the virtual screening of kinase inhibitors, while the fourth WDI database is for comparison since it covers a wide range of known chemical space. Based on the kinase-likeness score, a kinase-focused library is also developed and tested against three different kinase targets selected from three different branches of the human kinome tree. CONCLUSIONS: Our proposed methodology is one of the first that explores how the narrow chemical space of kinase inhibitors and its relevant physicochemical information can be utilized to build kinase-focused libraries and prioritize pre existing compound databases for screening. We have shown that focused libraries generated by filtering compounds using the kinase-likeness score have, on average, better docking scores than an equivalent number of randomly selected compounds. Beyond library design, our findings also impact the broader efforts to identify kinase inhibitors by screening pre-existing compound libraries. Currently, the NCI library is the most commonly used database for screening kinase inhibitors. Our research suggests that other libraries, such as MLSMR, are more kinase-like and should be given priority in kinase screenings. PMID- 22316382 TI - Measles virus, immune control, and persistence. AB - Measles remains one of the most important causes of child morbidity and mortality worldwide with the greatest burden in the youngest children. Most acute measles deaths are owing to secondary infections that result from a poorly understood measles-induced suppression of immune responses. Young children are also vulnerable to late development of subacute sclerosing panencephalitis, a progressive, uniformly fatal neurologic disease caused by persistent measles virus (MeV) infection. During acute infection, the rash marks the appearance of the adaptive immune response and CD8(+) T cell-mediated clearance of infectious virus. However, after clearance of infectious virus, MeV RNA persists and can be detected in blood, respiratory secretions, urine, and lymphoid tissue for many weeks to months. This prolonged period of virus clearance may help to explain measles immunosuppression and the development of lifelong immunity to re infection, as well as occasional infection of the nervous system. Once MeV infects neurons, the virus can spread trans-synaptically and the envelope proteins needed to form infectious virus are unnecessary, accumulate mutations, and can establish persistent infection. Identification of the immune mechanisms required for the clearance of MeV RNA from multiple sites will enlighten our understanding of the development of disease owing to persistent infection. PMID- 22316386 TI - Nailing Burkitt lymphoma. PMID- 22316387 TI - Multiplex targeted proteomic assay for biomarker detection in plasma: a pancreatic cancer biomarker case study. AB - Biomarkers are most frequently proteins that are measured in the blood. Their development largely relies on antibody creation to test the protein candidate performance in blood samples of diseased versus nondiseased patients. The creation of such antibody assays has been a bottleneck in biomarker progress due to the cost, extensive time, and effort required to complete the task. Targeted proteomics is an emerging technology that is playing an increasingly important role to facilitate disease biomarker development. In this study, we applied a SRM based targeted proteomics platform to directly detect candidate biomarker proteins in plasma to evaluate their clinical utility for pancreatic cancer detection. The characterization of these protein candidates used a clinically well-characterized cohort that included plasma samples from patients with pancreatic cancer, chronic pancreatitis, and healthy age-matched controls. Three of the five candidate proteins, including gelsolin, lumican, and tissue inhibitor of metalloproteinase 1, demonstrated an AUC value greater than 0.75 in distinguishing pancreatic cancer from the controls. In addition, we provide an analysis of the reproducibility, accuracy, and robustness of the SRM-based proteomics platform. This information addresses important technical issues that could aid in the adoption of the targeted proteomics platform for practical clinical utility. PMID- 22316388 TI - Stevioside enhances apoptosis induced by serum deprivation in PC12 cells. AB - In the laboratory, using a PC12 cell system, studies have been conducted on the effects of various chemicals on apoptosis, as it is considered to be an essential part of normal development, maintenance, and defense in organisms. Stevioside is a natural sweetener extracted from the leaves of Stevia rebaudiana. Since it is widely used as a sugar replacement, it was decided to evaluate the toxicological effects of low concentrations of stevioside on apoptosis induced by serum deprivation using the PC12 cell system. It was found that based on data from DNA electrophoresis and TUNEL signal assays stevioside enhanced apoptosis induced by serum deprivation. This enhancement was caused by increased expression of Bax and of cytochrome c released into the cytosol. These findings suggest that stevioside affects the regulation of the normal apoptotic condition. Further investigation will be needed to clarify the detailed mechanism of the enhancement due to the treatment with stevioside. PMID- 22316389 TI - Platelet signaling-a primer. AB - OBJECTIVE: To review the receptors and signal transduction pathways involved in platelet plug formation and to highlight links between platelets, leukocytes, endothelium, and the coagulation system. DATA SOURCES: Original studies, review articles, and book chapters in the human and veterinary medical fields. DATA SYNTHESIS: Platelets express numerous surface receptors. Critical among these are glycoprotein VI, the glycoprotein Ib-IX-V complex, integrin alpha(IIb) beta(3) , and the G-protein-coupled receptors for thrombin, ADP, and thromboxane. Activation of these receptors leads to various important functional events, in particular activation of the principal adhesion receptor alpha(IIb) beta(3) . Integrin activation allows binding of ligands such as fibrinogen, mediating platelet-platelet interaction in the process of aggregation. Signals activated by these receptors also couple to 3 other important functional events, secretion of granule contents, change in cell shape through cytoskeletal rearrangement, and procoagulant membrane expression. These processes generate a stable thrombus to limit blood loss and promote restoration of endothelial integrity. CONCLUSIONS: Improvements in our understanding of how platelets operate through their signaling networks are critical for diagnosis of unusual primary hemostatic disorders and for rational antithrombotic drug design. PMID- 22316390 TI - Management of Turner's syndrome in adult life: case-series and systematic review. AB - OBJECTIVE: To assess the symptoms and outcomes of clinical management in adult patients with Turner's Syndrome. DESIGN: Retrospective case-series and systematic review of the literature. SETTING: Gynaecological Endocrinology Unit in a teaching hospital. PATIENTS: Patients followed in the Gynaecological Endocrinology Unit. INTERVENTIONS: Review of medical records and a computer search via several databases to identify journals relevant to the subject were performed. MAIN OUTCOME MEASURES: Final height, weight, previous treatments with growth hormone, cardiac or renal malformations, metabolic profile, and additional treatment for osteoporosis. RESULTS: Thirty-one patients were analysed. Differences in final height were found between groups with monosomy and other karyotypes. Four patients bore congenital cardiac malformations, and six, renal congenital malformations. Nine patients had a previous diagnosis of hypercholesterolemia. The most abnormal hepatic parameter was GGT, with fifteen patients having values over the normality limit. Ten patients were receiving treatment for osteopenia or osteoporosis. CONCLUSIONS: This case-series provides recommendations for the management of adult patients with Turner's syndrome and insight into the different medical complaints of this syndrome. A link between karyotypes and clinical features suggests a novel hypothesis to explain the different phenotypes and clinical abnormalities of these patients. PMID- 22316391 TI - Effective components screening and anti-myocardial infarction mechanism study of the Chinese medicine NSLF6 based on "system to system" mode. AB - BACKGROUND: Shuanglong formula (SLF), a Chinese medicine composed of panax ginseng and salvia miltiorrhiza exhibited significant effect in the treatment of myocardial infarction (MI) in clinical. Because of the complex nature and lack of stringent quality control, it's difficult to explain the action mechanism of SLF. METHOD: In this study, we present a "system to system" (S2S) mode. Based on this mode, SLF was simplified successively through bioactivity-guided screening to achieve an optimized minimal phytochemical composition (new formula NSLF6) while maintaining its curative effect for MI. RESULTS: Pharmacological test combining with the study of systems biology show that NSLF6 has activity for treatment MI through synergistic therapeutic efficacies between total ginsenosides and total salvianolic acids via promoting cardiac cell regeneration and myocardial angiogenesis, antagonistic myocardial cell oxidative damage. CONCLUSIONS: The present S2S mode may be an effective way for the discovery of new composite drugs from traditional medicines. PMID- 22316392 TI - Plasma concentrations of caspofungin at two different dosage regimens in a patient with hepatic dysfunction. AB - The currently recommended dosage regimen of caspofungin (50 mg/day) was developed for patients with invasive candidiasis. With invasive aspergillosis, successful outcomes occur in less than half the patients. We evaluate the pharmacokinetics in a patient with elevated liver enzyme levels after liver transplantation, who received caspofungin for the treatment of aspergillosis. Plasma concentrations of caspofungin were monitored at 2 different dosage regimens. The area under the concentration-time curve (AUC) at a dosage of 70 mg was 191 mg h/L and was associated with an increase in liver enzymes. After dose reduction to 50 mg with an AUC of 100 mg h/L, liver enzymes normalized. In conclusion, caspofungin plasma concentrations may be helpful to evaluate exposure and reduce the need for off label dosing. PMID- 22316394 TI - Increased stability of glycol-terminated self-assembled monolayers for long-term patterned cell culture. AB - Self-assembled monolayers (SAMs) are widely used to confine proteins and cells to a pattern to study cellular processes and behavior. To fully explore some of these phenomena, it is necessary to control cell growth and confinement for several weeks. Here, we present a simple method by which protein and cellular confinement to a pattern can be maintained for more than 35 days. This represents a significant increase in pattern stability compared to previous monolayer systems and is achieved using an amide-linked glycol monomer on 50 A titanium/100 A gold-coated glass coverslips. In addition, this study provides insight into the method of SAM degradation and excludes interfacial mixing of the monomers and blooming of the adlayer as major mechanisms for SAM degradation. PMID- 22316395 TI - p53-Mdm2 inhibitors: patent review (2009 - 2010). AB - INTRODUCTION: p53 plays a central role in protecting the integrity of the genome. Its activity is ubiquitously lost in cancers, either by inactivation of its protein (p53 pathway) or by mutation in the p53 gene, thereby indicating its importance in understanding cancer and as a therapeutic target. Activated p53 is known to induce cell cycle arrest thereby leading to apoptosis and has been the subject of intensive research in the area of medicinal chemistry. Efforts are in progress to synthesize a variety of scaffolds that could inhibit the p53-Mdm2 interaction by binding to Mdm2 in the region where p53 is likely to bind. These molecules have the potential to be developed as anticancer drug candidates and have been largely explored by both academia and industry. Interestingly, some of these molecules are in the early stage of clinical trials. AREAS COVERED: Areas covered in this review include patents relating to p53-Mdm2 inhibitors during the time period 2009 - 2010. The focus of the review was on small-molecule inhibitors. EXPERT OPINION: Inducing apoptosis in cancerous cells by the activation of p53 is an area that is being actively explored. There are strong indications that it could become a therapeutic method for the treatment of cancer. As a result, extensive research is being performed by both academia and industry. It is observed that small molecules that are present in early clinical trials are expected to be developed as potential drugs for cancer therapy. PMID- 22316397 TI - Changes in antipsychotic medication use after implementation of a Medicaid mental health carve-out in the US. AB - BACKGROUND: Many Medicaid programmes now offer behavioural healthcare through managed care organizations. Medicaid programmes are concerned about carve-outs because the use of non-included services may rise, limiting the efficiencies anticipated with the implementation of managed care. There also exist concerns that patients with serious mental illness may receive reduced care through managed care and consequently have poorer outcomes. OBJECTIVE: This study examined prescription drug utilization among Medicaid recipients with the implementation of a mental health carve-out plan in Florida. In particular, this study examined short-run changes in the utilization of antipsychotic medications among individuals diagnosed with schizophrenia or episodic mood disorders with the implementation of Prepaid Mental Health Plans (PMHPs) in Florida Medicaid. METHODS: This study used Medicaid data from 38 counties in Florida that implemented the PMHP programme in 2005 and 2006. The sample was limited to individuals aged<=64 years who were continuously enrolled in Medicaid. Individuals were required to have at least two diagnoses of schizophrenia, episodic mood disorders, delusional disorders or other nonorganic disorders (three-digit International Classification of Diseases, Ninth Revision [ICD-9] code of 295-298). Five different outcome measures were examined on a monthly basis for the 6 months pre- and post-PMHP implementation: penetration; adherence; Medicaid expenditures for antipsychotics; polypharmacy (multiple antipsychotic medications); and whether dosing was within guidelines. Generalized estimating equations were used to estimate associations between individual and insurance characteristics, and the outcome variables. The analyses were conducted using SAS procedure GENMOD. Empirical (robust) standard errors were calculated to account for repeated observations on the same individual. RESULTS: There were 153,720 monthly observations for the 12,810 people in the sample. Seventy-four percent of the sample was aged between 21 and 54 years, while 65% were female, 30% White, 14% Black and 44% Hispanic. The large proportion of Hispanics stems from the introduction of the PMHP programme in Dade County (Miami). The results indicate the implementation of the PMHP was associated with increased penetration, but reduced adherence, polypharmacy and expenditures by the Medicaid agency. There was no change in the likelihood of prescriptions being written within recommended dosage ranges. CONCLUSION: The introduction of the PMHP was associated with short run changes in medication utilization among individuals with serious mental illness. PMID- 22316398 TI - Medicaid and privately financed orthodontic patients have similar occlusal and psychosocial outcomes. AB - OBJECTIVE: This study compares occlusal and psychosocial outcomes from comprehensive orthodontic treatment in Medicaid (MC) and privately financed (private pay, PP) patients. METHODS: Two cohorts received comprehensive orthodontics: MC (n = 66); PP (n = 60). A calibrated, blinded examiner scored dental casts at baseline (pretreatment, T1) and after completing 2 years of treatment (posttreatment, T2) using the Peer Assessment Rating (PAR) and the Index of Complexity, Outcome, and Need (ICON). The prevalence of patients in the validated ICON categories for treatment need, complexity, and improvement were calculated. Questionnaires to assess body image (BI) and expectations/experiences were administered. Occlusal measures at T2 were compared after adjustment for baseline characteristics. Psychosocial measures were compared between and within groups. Occlusal and psychosocial associations were evaluated. RESULTS: MC was 1.3 years younger (P < 0.001) and had worse malocclusions at baseline (PAR 32 versus 25; P < 0.001); (ICON 64 versus 56; P = 0.06). After adjustment for age and initial severity, estimated average differences between groups at T2 (MC-PP) were slight: 1.5 [95 percent confidence interval (CI) -2.9, 5.9] and 2.4 (95 percent CI -4.4, 8.9) for PAR and ICON, respectively. More PP completed treatment under 2 years (85 percent versus 62 percent; P = 0.03). At baseline, both groups needed treatment, but MC malocclusions were more complex (P = 0.05). At T2, both groups were acceptable and there were no differences in ICON improvement categories. Group differences in psychosocial measures and associations between psychosocial and occlusal measures were evident in the "teeth" domain but weak or lacking elsewhere. CONCLUSIONS: Occlusal and psychosocial outcomes from orthodontics in MC and PP were comparable, despite worse MC malocclusions at baseline. PMID- 22316400 TI - Thermochemical properties of selenium fluorides, oxides, and oxofluorides. AB - The bond dissociation energies (BDEs), fluoride and fluorocation affinities, and electron affinities of SeF(n) (n = 1-6), SeOF(n) (n = 0-4), and SeO(2)F(n) (n = 0 2) have been predicted with coupled cluster CCSD(T) theory extrapolated to the complete basis set limit. To achieve near chemical accuracy, additional corrections were added to the complete basis set binding energies based on frozen core coupled cluster theory energies. These included corrections for core-valence effects, scalar relativistic effects, for first-order atomic spin-orbit effects, and vibrational zero point energies. The adiabatic BDEs contain contributions from product reorganization energies and, therefore, can be much smaller than the diabatic BDEs and can vary over a wide range. For thermochemical calculations, the adiabatic values must be used, whereas for bond strength and kinetic considerations, the diabatic values should be used when only small displacements of the atoms without change of the geometry of the molecule are involved. The adiabatic Se-F BDEs of SeF(n) (n = 1-6) are SeF(6) = 90, SeF(5) = 27, SeF(4) = 93, SeF(3) = 61, SeF(2) = 86, and SeF = 76 kcal/mol, and the corresponding diabatic values are SeF(6) = 90, SeF(5) = 88, SeF(4) = 93, SeF(3) = 74, SeF(2) = 86, and SeF = 76 kcal/mol. The adiabatic Se-O BDEs of SeO(n) (n = 1-3), SeOF(n) (n = 1-4), and SeO(2)F(n) (n = 1,2) range from 23 to 107 kcal/mol, whereas the diabatic ones range from 62 to 154 kcal/mol. The adiabatic Se-F BDEs of SeOF(n) (n = 1-4) and SeO(2)F(n) (n = 1,2) range from 20 to 88 kcal/mol, whereas the diabatic ones range from 73 to 112 kcal/mol. The fluoride affinities of SeF(n), (n = 1-6), SeO(n), (n = 1-3), SeOF(n), (n = 1-4), and SeO(2)F(n) (n = 1,2) range from 15 to 121 kcal/mol, demonstrating that the Lewis acidity of these species covers the spectrum from very weak (SeF(6)) to very strong (SeO(3)) acids. The electron affinities which are a measure of the oxidizing power of a species, span a wide range from 1.56 eV in SeF(4) to 5.16 eV in SeF(5) and for the free radicals are much higher than for the neutral molecules. Another interesting feature of these molecules and ions stems from the fact that many of them possess both a Se free valence electron pair and a free unpaired valence electron, raising the questions of their preferred location and their influence on the Se-F and Se?O bond strengths. PMID- 22316399 TI - Group B streptococcal carriage, serotype distribution and antibiotic susceptibilities in pregnant women at the time of delivery in a refugee population on the Thai-Myanmar border. AB - BACKGROUND: Group B Streptococcus (GBS) is the leading cause of neonatal sepsis in the developed world. Little is known about its epidemiology in the developing world, where the majority of deaths from neonatal infections occur. Maternal carriage of GBS is a prerequisite for the development of early onset GBS neonatal sepsis but there is a paucity of carriage data published from the developing world, in particular South East Asia. METHODS: We undertook a cross sectional study over a 13 month period in a remote South East Asian setting on the Thai Myanmar border. During labour, 549 mothers had a combined vaginal rectal swab taken for GBS culture. All swabs underwent both conventional culture as well as PCR for GBS detection. Cultured GBS isolates were serotyped by latex agglutination, those that were negative or had a weak positive reaction and those that were PCR positive but culture negative were additionally tested using multiplex PCR based on the detection of GBS capsular polysaccharide genes. RESULTS: The GBS carriage rate was 12.0% (95% CI: 9.4-15.0), with 8.6% positive by both culture and PCR and an additional 3.5% positive by PCR alone. Serotypes, Ia, Ib, II, III, IV, V, VI and VII were identified, with II the predominant serotype. All GBS isolates were susceptible to penicillin, ceftriaxone and vancomycin and 43/47 (91.5%) were susceptible to erythromycin and clindamycin. CONCLUSIONS: GBS carriage is not uncommon in pregnant women living on the Thai Myanmar border with a large range of serotypes represented. PMID- 22316403 TI - Postoperative evaluation of grafted bone in alveolar cleft using three dimensional computed tomography data. AB - Objective : Postoperative evaluation of bone formation in the alveolar cleft by computed tomography imaging has been reported. We quantitatively evaluated bone grafts in the alveolar cleft preoperatively and postoperatively using three dimensional data and superimposition of images. Subjects : A total of 12 patients with complete unilateral cleft lip and palate (six left-sided and six right sided) were studied. Methods : Helical computed tomography scans were taken immediately before surgery and at 6 months after surgery and the DICOM files obtained were processed using Mimics and 3-matic software for three-dimensional data analysis. The preoperative and postoperative computed tomography data were superimposed, and the position and length of the unerupted canines and width of the alveolar cleft measured. Results : Strong and significant correlations were observed between bone formation in the alveolar cleft bone graft region and preoperative canine position (r = -.766, p < .01) and canine length (r = .681, p < .05). Stepwise multiple regression analysis demonstrated that only the preoperative canine position was independently and significantly correlated with bone formation in the alveolar cleft. Conclusion : These results indicate that the optimal timing for surgery is when the canine cusp is close to the alveolar plane. PMID- 22316404 TI - Biophysical assessment of aquaporin-9 as principal facilitative pathway in mouse liver import of glucogenetic glycerol. AB - BACKGROUND INFORMATION: Lipolytic glycerol, released from adipocytes, flows through the bloodstream to the liver, where its utilisation in supplying hepatocyte gluconeogenesis is rate-limited by the permeation step. An aquaglyceroporin expressed in hepatocytes, aquaporin-9 (AQP9), has been often linked to liver uptake of glycerol. However, the truthfulness of this postulation and the potential existence of additional pathways of glycerol import by hepatocytes have never been assessed directly. Here, we define the identity and extent of liver glycerol transport and evaluate the correlation between hepatic AQP9 expression and glycerol permeability (P(gly) ) in AQP9(+/+) wild-type mice in different nutritional states and circulating insulin levels. The liver P(gly) of AQP9 null mice is also assessed. RESULTS: By stopped-flow light scattering, facilitated diffusion of glycerol into hepatocytes was indicated by the low Arrhenius activation energy (3.5 kcal/mol) and strong inhibition by phloretin, an AQP9 blocker, that characterised the transport. Although fasting markedly increased hepatic AQP9, a straight parallelism was seen both in quantitative and time-space terms between P(gly) and AQP9 protein in AQP9(+/+) mice kept in fed or fasted/refed states. In line with these findings, the highest P(gly) (P(gly) ~ 14.0 * 10(-6) cm/s at 20 degrees C) at 18-h fasting coincided with the highest percent of phloretin inhibition (63%). Besides being markedly lower than that in AQP9(+/+) mice, the liver P(gly) of the AQP9 null mice did not increase during fasting. Reverse-transcription PCR analysis showed lack of compensation by AQP3 and AQP7, the other known murine glycerol facilitators, in AQP9 null mice. CONCLUSIONS: Overall, these results experimentally prove major functional significance for AQP9 in maximising liver glycerol import during states requiring increased glucose production. If any, alternative facilitated pathways would be of minor importance in transporting glucogenetic glycerol into hepatocytes during starvation. Refining the understanding of liver AQP9 in metabolic and energy homeostasis may reveal helpful for therapeutic purposes. PMID- 22316405 TI - Toxic prefibrillar alpha-synuclein amyloid oligomers adopt a distinctive antiparallel beta-sheet structure. AB - Parkinson's disease is an age-related movement disorder characterized by the presence in the mid-brain of amyloid deposits of the 140-amino-acid protein AS (alpha-synuclein). AS fibrillation follows a nucleation polymerization pathway involving diverse transient prefibrillar species varying in size and morphology. Similar to other neurodegenerative diseases, cytotoxicity is currently attributed to these prefibrillar species rather than to the insoluble aggregates. Nevertheless, the underlying molecular mechanisms responsible for cytotoxicity remain elusive and structural studies may contribute to the understanding of both the amyloid aggregation mechanism and oligomer-induced toxicity. It is already recognized that soluble oligomeric AS species adopt beta-sheet structures that differ from those characterizing the fibrillar structure. In the present study we used ATR (attenuated total reflection)-FTIR (Fourier-transform infrared) spectroscopy, a technique especially sensitive to beta-sheet structure, to get a deeper insight into the beta-sheet organization within oligomers and fibrils. Careful spectral analysis revealed that AS oligomers adopt an antiparallel beta sheet structure, whereas fibrils adopt a parallel arrangement. The results are discussed in terms of regions of the protein involved in the early beta-sheet interactions and the implications of such conformational arrangement for the pathogenicity associated with AS oligomers. PMID- 22316406 TI - Special suicide and suicide prevention section of the Journal of American College Health. PMID- 22316407 TI - Help seeking and treatment use among suicidal college students. AB - OBJECTIVES: Many suicidal college students do not receive mental health treatment, and the reasons for this are not fully understood. This study examines how attitudes, beliefs, and social network factors relate to help seeking among suicidal students. PARTICIPANTS: A random sample of 8,487 undergraduate and graduate students from 15 US universities participated. METHODS: A Web-based survey administered in spring 2009 examined correlates of mental health service utilization among students reporting serious thoughts of suicide in the previous year (n = 543). RESULTS: Correlates of treatment use included perceived need, beliefs that treatment is effective, contact with service users, lower personal stigma, higher perceived stigma, fewer positive relationships, and sexual minority or Caucasian identity. CONCLUSIONS: Help seeking among suicidal students is associated with a range of personal and social network factors. Campus strategies to enhance help seeking should be tailored to address identified facilitators and barriers to treatment use among target populations. PMID- 22316408 TI - Race and ethnic differences in hope and hopelessness as moderators of the association between depressive symptoms and suicidal behavior. AB - OBJECTIVE: The authors examined trait hope and hopelessness as potential moderators of the association between depressive symptoms and suicidal behavior. PARTICIPANTS: A diverse sample of 372 college students. METHODS: Depressive symptoms, hopelessness (Beck Hopelessness Scale), trait hope (Trait Hope Scale), and suicidal behaviors were assessed. Trait hope is defined as confidence in the ability to identify and attain goals, whereas hopelessness encompasses future attitudes and motivation loss. RESULTS: In independent models, low hopelessness buffered the association between depressive symptoms and suicidal behavior for our whole sample, blacks, and whites, whereas trait hope buffered for Hispanics and whites. Examined simultaneously, hope remained a significant moderator only in whites and hopelessness only in blacks. These findings suggest that etiological and outcome correlates of hope and hopelessness may differ by ethnicity. CONCLUSIONS: These findings may have implications for development of culturally targeted interventions for college students that strive to simultaneously reduce hopelessness and bolster hopefulness. PMID- 22316409 TI - The relationship of level of positive mental health with current mental disorders in predicting suicidal behavior and academic impairment in college students. AB - OBJECTIVE: To investigate whether level of positive mental health complements mental illness in predicting students at risk for suicidal behavior and impaired academic performance. PARTICIPANTS: A sample of 5,689 college students participated in the 2007 Healthy Minds Study and completed an Internet survey that included the Mental Health Continuum-Short Form and the Patient Health Questionnaire screening scales for depression and anxiety disorders, questions about suicide ideation, plans, and attempts, and academic impairment. RESULTS: Just under half (49.3%) of students were flourishing and did not screen positive for a mental disorder. Among students who did, and those who did not, screen for a mental disorder, suicidal behavior and impaired academic performance were lowest in those with flourishing, higher among those with moderate, and highest in those with languishing mental health. CONCLUSIONS: Positive mental health complements mental disorder screening in mental health surveillance and prediction of suicidal behavior and impairment of academic performance. PMID- 22316410 TI - The impact of experiential exercises on communication and relational skills in a suicide prevention gatekeeper-training program for college resident advisors. AB - OBJECTIVE: In an effort to identify students at risk for suicide, many colleges are implementing suicide prevention training for campus gatekeepers. This study evaluated the efficacy of a 3-hour, experiential-based gatekeeper training that included an emphasis on enhancing communication skills and relational connection in addition to the didactic foci of standard gatekeeper training. PARTICIPANTS: Sixty-five college student resident advisors (RAs) were trained with Campus Connect. METHODS: The training was dismantled to examine the specific contribution of experiential exercises on training outcomes. RESULTS: Compared to didactic training alone, following participation in experiential exercises RAs' training outcome scores exhibited additional improvement on the Suicide Intervention Response Inventory-2 and a 14-item self-report measure of self efficacy for specific suicide- and crisis-related knowledge and skills. CONCLUSIONS: In gatekeeper training, experiential exercises emphasizing awareness and empathic responding and practice of these skills contribute to an improvement in crisis response skills above and beyond that of didactic training alone. PMID- 22316411 TI - Drivers of disparity: differences in socially based risk factors of self injurious and suicidal behaviors among sexual minority college students. AB - Lesbian, gay, and bisexual (ie, sexual minority) populations have increased prevalence of both self-injurious and suicidal behaviors, but reasons for these disparities are poorly understood. OBJECTIVE: To test the association between socially based stressors (eg, victimization, discrimination) and self-injurious behavior, suicide ideation, and suicide attempt. PARTICIPANTS: A national sample of college-attending 18- to 24-year-olds. METHODS: Random or census samples from postsecondary educational institutions that administered the National College Health Assessment during the Fall 2008 and Spring 2009 semesters. RESULTS: Sexual minorities reported more socially based stressors than heterosexuals. Bisexuals exhibited greatest prevalence of self-injurious and suicidal behaviors. In adjusted models, intimate partner violence was most consistently associated with self-injurious behaviors. CONCLUSIONS: Sexual minorities' elevated risks of self injurious and suicidal behaviors may stem from higher exposure to socially based stressors. Within-group differences among sexual minorities offer insight to specific risk factors that may contribute to elevated self-injurious and suicidal behaviors in sexual minority populations. PMID- 22316412 TI - Human papillomavirus vaccine intent and uptake among female college students. AB - OBJECTIVE: To examine human papillomavirus (HPV) vaccine intent and the effect of an educational intervention on vaccine uptake among female college students. PARTICIPANTS: Females aged 18 to 26 attending a university health service gynecology clinic (n = 256). METHODS: Participants were randomized to receive either HPV-specific education with a mailed reminder or standard care. Predictors of HPV vaccine intent and uptake at 6 months following enrollment were identified. RESULTS: At baseline, 41% intended to undergo HPV vaccination. Participants who were currently sexually active and lacked supplemental health insurance had decreased intent. Perceived parental approval regarding HPV vaccination, perceived vulnerability to HPV infection, and belief in health benefits of HPV vaccine were associated with increased intent. HPV vaccine uptake was low (5.5%) and did not differ by study group. However, baseline intent was significantly associated with HPV vaccine uptake. CONCLUSIONS: Interventions to increase HPV vaccine uptake in college students should address HPV-related beliefs and broader barriers to vaccination. PMID- 22316413 TI - An assessment of America's tobacco-free colleges and universities. AB - OBJECTIVE: This study examined the extent to which US campuses identified as "100% tobacco-free" by the American Lung Association of Oregon adhered to the American College Health Association's the most recent guidelines and recommendations promoting tobacco-free environments in colleges and universities. PARTICIPANTS: A key informant from 162 of 175 institutions (92.6% response rate) completed an online survey between January 2010 and February 2010. METHODS: The variables under study were assessed via a cross-sectional research design. Participants completed a 35-item survey regarding their school's tobacco policies, procedures, and enforcement practices. RESULTS: Although the vast majority of schools had written policies and procedures in place, schools with current policies were the most compliant. Numerous opportunities for improved adherence were identified in the results. CONCLUSIONS: Findings from this study may help institutions in the development and implementation of a new tobacco policy, as well as strengthen policies among existing tobacco-free schools. PMID- 22316414 TI - The prevalence of stalking among college students: the disparity between researcher- and self-identified victimization. AB - OBJECTIVE: Researchers examined the prevalence of self-identified and researcher identified stalking victimization among college students. PARTICIPANTS AND METHODS: A representative sample of 1,573 (70.1% female; 29.9% male) student respondents completed an online stalking questionnaire. RESULTS: Overall, 12% self-identified as having been stalked. Additionally, 42.5% (45.4% female; 35.7% male) of students reported experiencing at least 1 behavioral indicator of stalking victimization; however, only 24.7% of those self-identified as being stalked (25.6% female; 22.0% male). CONCLUSIONS: Stalking is a serious problem in the college community. A concern that needs to be addressed is the disparity between the number of those who met the behavioral criteria for stalking victimization, but who did not self-identify as a victim. The consequences of stalking victimization are highlighted. Recommendations for addressing this issue on campus are detailed in a plan that may help improve the retention, progression, and graduation rates for stalking victims. PMID- 22316415 TI - F.O.R.E.play: the utility of brief sexual health interventions among college students. AB - OBJECTIVES: The authors aimed to determine the most effective brief sexual health intervention for college students, while also evaluating students' preferences for learning about sexual health, in order to develop a university program. METHODS: A total of 302 students enrolled in an introductory college course participated and were randomly assigned to 1 of 3 brief interventions during a regularly scheduled class and completed pre- and postsurveys assessing knowledge, motivation to use condoms, and condom self-efficacy. RESULTS: Findings indicated that having an actual person in charge of the learning process resulted in higher knowledge gains and highlighted a student preference for discussion-based learning, viewing pictures of sexually transmitted infections, and hearing real life experiences about the consequences of unsafe sex. CONCLUSIONS: These findings will be used to tailor a future intervention targeting college students for use with freshmen students at this university. PMID- 22316416 TI - Medication abortion within a student health care clinic: a review of the first 46 consecutive cases. AB - OBJECTIVE: Medication abortion with mifepristone and misoprostol has been available in the United States since 2000. The authors reviewed the first 46 medication abortion cases conducted at a university-based student health care clinic to determine the safety and feasibility of medication abortion in this type of clinical setting. PARTICIPANTS: Female patients presenting for medication abortion at a student health care clinic between October 1, 2006, and April 1, 2009. METHODS: Retrospective consecutive case review. RESULTS: Successful completion not requiring uterine aspiration occurred in 85% of the cases that were not lost to follow-up. Six cases (15%) required uterine aspiration for completion: 3 underwent uterine aspiration only; 3 had aspiration after failing an additional dose of misoprostol. Only 1 patient visited the emergency room. There were no hospitalizations. CONCLUSIONS: Medication abortion services in a student health care clinic are safe and feasible. However, additional treatment may be required with some patients. PMID- 22316417 TI - Therapeutic options for immune-mediated thrombocytopenia. AB - OBJECTIVE: To review the therapeutic options for immune-mediated thrombocytopenia (IMT). DATA SOURCES: Original research publications and review articles using the PubMed search engine for the phrases "immune-mediated thrombocytopenia" or "immune thrombocytopenic purpura" or "immune thormbocytopenia." VETERINARY AND HUMAN DATA SYNTHESIS: There are a number of therapeutic options for adult-onset immune thrombocytopenia in human medicine with demonstrated efficacy in clinical studies although corticosteroids and immunoglobulin therapy remain the first-line medical treatments. Thrombopoietin receptor agonist therapy and, to a lesser extent, rituximab have shown great promise in initial clinical trials and may become standard of care in human medicine for the management of IMT. Therapeutic options in veterinary medicine are less diverse and only vincristine and human intravenous immunoglobulin therapies have been evaluated in controlled clinical studies. CONCLUSIONS: There are a number of therapeutic options in the management of IMT veterinary medicine, most of which have not been investigated in clinical studies. Further research is warranted to best identify the optimal treatment strategy for IMT in veterinary patients. PMID- 22316418 TI - Versatile multilevel soft lithography method with micrometer alignment using all flexible rubber stamps and moire fringe technique. AB - Soft lithography has gathered wide interest for the fabrication of unconventional micrometer and nanometer-sized structures and devices. Nevertheless, accurate alignment is essential to achieve multilevel soft lithography. Because of the soft nature of the stamp materials, such as soft polydimethylsiloxane, they are susceptible to mechanical distortions, which lower the registration accuracy. To reduce the distortions we backed the stamp with a polymer foil and minimized the overall forces applied to the stamp. We furthermore employed an alignment method using additive type moire fringe technique that is easy to implement and does not require extensive processing steps. The alignment results show less than 1 MUm misalignment when the stamp is brought again onto a previously structured rigid template. When performing two consecutive lithography steps by transfer printing of thin gold films, we were able to obtain average registration accuracy of 1.3 MUm over an area of 400 mm(2). This method is versatile and can be used for several soft lithography techniques. Better results can be obtained with smaller moire gratings and the use of harder materials. PMID- 22316419 TI - Probing lactate dehydrogenase activity in tumors by measuring hydrogen/deuterium exchange in hyperpolarized l-[1-(13)C,U-(2)H]lactate. AB - (13)C magnetic resonance spectroscopy and spectroscopic imaging measurements of hyperpolarized (13)C label exchange between exogenously administered [1 (13)C]pyruvate and endogenous lactate, catalyzed by lactate dehydrogenase (LDH), has proved to be a powerful approach for probing tissue metabolism in vivo. This experiment has clinical potential, particularly in oncology, where it could be used to assess tumor grade and response to treatment. A limitation of the method is that pyruvate must be administered in vivo at supra-physiological concentrations. This problem can be avoided by using hyperpolarized [1 (13)C]lactate, which can be used at physiological concentrations. However, sensitivity is limited in this case by the relatively small pyruvate pool size, which would result in only low levels of labeled pyruvate being observed even if there was complete label equilibration between the lactate and pyruvate pools. We demonstrate here a more sensitive method in which a doubly labeled lactate species can be used to measure LDH-catalyzed exchange in vivo. In this experiment exchange of the C2 deuterium label between injected hyperpolarized l-[1-(13)C,U (2)H]lactate and endogenous unlabeled lactate is observed indirectly by monitoring phase modulation of the spin-coupled hyperpolarized (13)C signal in a heteronuclear (1)H/(13)C spin-echo experiment. PMID- 22316420 TI - Evaluation of blood-brain barrier transport and CNS drug metabolism in diseased and control brain after intravenous L-DOPA in a unilateral rat model of Parkinson's disease. AB - BACKGROUND: Changes in blood-brain barrier (BBB) functionality have been implicated in Parkinson's disease. This study aimed to investigate BBB transport of L-DOPA transport in conjunction with its intra-brain conversion, in both control and diseased cerebral hemispheres in the unilateral rat rotenone model of Parkinson's disease. METHODS: In Lewis rats, at 14 days after unilateral infusion of rotenone into the medial forebrain bundle, L-DOPA was administered intravenously (10, 25 or 50 mg/kg). Serial blood samples and brain striatal microdialysates were analysed for L-DOPA, and the dopamine metabolites DOPAC and HVA. Ex-vivo brain tissue was analyzed for changes in tyrosine hydroxylase staining as a biomarker for Parkinson's disease severity. Data were analysed by population pharmacokinetic analysis (NONMEM) to compare BBB transport of L-DOPA in conjunction with the conversion of L-DOPA into DOPAC and HVA, in control and diseased cerebral hemisphere. RESULTS: Plasma pharmacokinetics of L-DOPA could be described by a 3-compartmental model. In rotenone responders (71%), no difference in L-DOPA BBB transport was found between diseased and control cerebral hemisphere. However, in the diseased compared with the control side, basal microdialysate levels of DOPAC and HVA were substantially lower, whereas following L-DOPA administration their elimination rates were higher. CONCLUSIONS: Parkinson's disease-like pathology, indicated by a huge reduction of tyrosine hydroxylase as well as by substantially reduced levels and higher elimination rates of DOPAC and HVA, does not result in changes in BBB transport of L-DOPA. Taking the results of this study and that of previous ones, it can be concluded that changes in BBB functionality are not a specific characteristic of Parkinson's disease, and cannot account for the decreased benefit of L-DOPA at later stages of Parkinson's disease. PMID- 22316421 TI - MR enterography to evaluate sub-clinical intestinal inflammation in children with spondyloarthritis. AB - BACKGROUND: Magnetic resonance enterography (MRE) is an established tool to evaluate for changes associated with inflammatory bowel disease (IBD), but has not been studied in sub-clinical IBD. We sought to evaluate the use of MRE in children with spondyloarthritis (SpA), who are at risk of having sub-clinical gut inflammation. METHODS: Children with juvenile idiopathic arthritis (JIA) with evidence of intestinal inflammation as evidence by an abnormal fecal calprotectin assay were offered MRE of their intestines. Flavored sports drink containing polyethylene glycol 3350 was used as oral contrast. Glucagon was used to arrest peristalsis. Patients were imaged in the prone position on a 1.5 T scanner. Heavily T2-weighted fat-suppressed coronal and axial images using breath-hold technique were obtained, followed by post-gadolinium fat-suppressed T1-weighted gradient echo images. RESULTS: We recruited five children with juvenile idiopathic arthritis (JIA); four had SpA, and one had poly-articular JIA. All five had evidence of intestinal inflammation based upon a positive fecal calprotectin assay and successfully completed the MRE. Three of the studies showed findings suggestive of IBD, including thickening and contrast uptake at the terminal ileum (TI) in one child, contrast uptake of the distal ileum in another, and prominent vasa recta and mesenteric lymph nodes in the third. The child with evidence of inflammatory changes at the TI underwent colonoscopy, which revealed inflammatory bowel disease limited to the TI. CONCLUSIONS: MRE can be used to evaluate for subclinical IBD in children with JIA. This protocol was safe and well-tolerated, and identified mild changes in three of the subjects. PMID- 22316422 TI - Fair enough? Inviting inequities in state health benefits. PMID- 22316423 TI - The value of federalism in defining essential health benefits. PMID- 22316424 TI - Changing knowledge and beliefs through an oral health pregnancy message. AB - OBJECTIVES: Pregnancy can be a critical and important period in which to intervene to improve oral health in both the mother and her child. This study examined an online approach for promoting awareness of oral health messages targeted at pregnant women, and whether this type of health messaging impacts oral health knowledge and beliefs. METHODS: The study was conducted in three parts: production and pilot testing of a brief commercial, Web site/commercial launch and testing, and dissemination and monitoring of the commercial on a video sharing site. The brief commercial and pre- and postsurveys were produced and pilot tested among a convenience sample of pregnant women (n = 13). The revised commercial and surveys were launched on a newly created Web site and monitored for activity. After 2 months, the commercial was uploaded to a popular video sharing Web site. RESULTS: Fifty-five individuals completed both the pre- and postsurveys after the Web site was launched. No one responded 100 percent correctly on the presurvey; 77.4 percent responded correctly about dental visits during pregnancy, 66.0 percent about cavity prevention, and 50.9 percent about transmission of bacteria by saliva. Most respondents recalled the correct information on the posttest; 100 percent or close to 100 percent accurately responded about visiting the dentist during pregnancy and preventing cavities, while 79.2 percent responded correctly to the transmission question. CONCLUSION: Social media can effectively provide dental health messages during pregnancy. This approach can play an important role in increasing awareness and improving oral health of both mother and child. PMID- 22316426 TI - Is a single dose of meningococcal serogroup C conjugate vaccine sufficient for protection? experience from the Netherlands. AB - BACKGROUND: The first meningococcal serogroup C (MenC) conjugate vaccine was licensed in 1999 and introduced in the United Kingdom. Countries that have implemented the MenC vaccine since then in their national immunisation programmes use different schedules. Nevertheless, all involved countries seem to experience substantial declines in the incidence of MenC disease. DISCUSSION: Since 2001, the MenC conjugate vaccine has been implemented in the Netherlands by offering a single dose to all children aged 14 months. Prior to the introduction of the vaccine into the national immunisation programme, a catch-up vaccination campaign was initiated in which a single dose of the MenC conjugate vaccine was offered to all children aged from 14 months up to and including 18 years. Since then, there has been no report of any case of MenC disease among immunocompetent vaccinees. Administration of a single dose of MenC conjugate vaccine after infancy could be beneficial considering the already complex immunisation schedules with large numbers of vaccinations in the first year of life. The present paper deals with the advantages and critical aspects of a single dose of the MenC conjugate vaccine. SUMMARY: A single dose of MenC conjugate vaccine at the age of 14 months in combination with a catch up vaccine campaign appeared to be a successful strategy to prevent MenC disease in the Netherlands, thereby confirming that a single dose of the vaccine could sufficiently protect against disease. Nevertheless, this approach can only be justified in countries with a relatively low incidence of serogroup C meningococcal disease in the first year of life. Furthermore, a good surveillance programme is recommended for timely detection of vaccine breakthroughs and outbreaks among non-vaccinees, since long-term protection after a single dose in the second year of life cannot currently be guaranteed. PMID- 22316427 TI - Can we replace the microscope with microarrays for diagnosis, prognosis and treatment of early breast cancer? AB - In recent years, molecular research has translated into remarkable changes for breast cancer diagnostics and therapeutics. Molecular tests such as Oncotype DX(r) and MammaPrint(r) have revolutionized the predictive and prognostic tools in the clinic. By stratifying the risk of recurrence for patients, the tests are able to provide clinicians with more information on the treatment outcomes of using chemotherapy, endocrine therapy or combination therapies for patients with genetic expression patterns. However, it is still questionable for clinical applications as some areas remain unclear; the true benefit still needs prospective evaluation. In this paper, the limitation and the possibility to replace traditional histopathologic features of molecular tests are discussed. At the moment, it seems there are still limitations that prevent microarrays from replacing the microscope for diagnosis, prognosis and treatment of early breast cancer. However, additional important clinical information is added to traditional histology and IHC determination of ER, PR and HER2 in terms of prognostic and predictive power. PMID- 22316428 TI - Radical mediated deoxygenation of inositol benzylidene acetals: conformational analysis, DFT calculations, and mechanism. AB - Xanthates of 1,3-benzylidene acetal derivatives of myo- and neo-inositols undergo dideoxygenation under Barton-McCombie conditions, as a result of intramolecular abstraction of the benzylidene acetal hydrogen and subsequent cleavage of the acetal ring. Scrutiny of structure of these bicyclic inositol derivatives shows that although the conformation of the two rings can vary depending on the configuration of the inositol ring and the phase in which the molecules are present, both the xanthates lead to the formation of the same dideoxyinositol. DFT calculations on these molecular systems suggest that neo-inositol derivatives undergo conformational change prior to radical formation while myo-inositol derivatives undergo conformational change subsequent to radical formation, during the deoxygenation reaction. A low barrier for intramolecular hydrogen transfer supports the extreme facility of this deoxygenation reaction. PMID- 22316430 TI - Potential energy surfaces for rearrangements of Berson trimethylenemethanes. AB - In this research, thermal rearrangements of the Berson trimethylenemethanes (Berson-TMMs) have been investigated by employing density functional theory (DFT) and high-level ab initio methods, such as the complete active space self consistent field (CASSCF), multireference second-order Moller-Plesset perturbation theory (MRMP2), multireference configuration interaction singles and doubles (MRCISD), and coupled-cluster singles and doubles with perturbative triples [CCSD(T)]. In all computations Pople's polarized triple-zeta split valence basis set, 6-311G(d,p), is utilized. The relevant portions of the lowest energy, singlet-spin potential energy surface of the C(4)H(6) (parent TMM), C(6)H(8) (Berson-TMMa), and C(8)H(12) (Berson-TMMc) chemical systems have been explored in order to determine the reaction energies and activation parameters accurately, with the ultimate objective of providing a theoretical account of experiments by Berson on TMMc. The nature of the orthogonal and the planar structures of the parent TMM have been clarified in this study. We have concluded that the orthogonal TMM (1)B(1) minimum has a C(2v) symmetry structure, and there is no pyramidalization in the unique methylene group. It lies at 13.9 kcal mol( 1) above the triplet minimum (3)B(2) at MRCISD level. The closed-shell (1)A(1) state of the planar TMM is not a true minimum but a transition structure (TS) for 180 degrees rotation of the unique methylene group in the orthogonal TMM minimum. It lies at 3.0 kcal mol(-1) above (1)B(1). The planar structures are also involved in the interchange of equivalent orthogonal TMMs (o(1), o(2), o(3)). Many features of the parent TMM are retained in TMMa and TMMc, despite the constraints imposed by the five-membered ring in the latter species. Thus, ring closure to the bicyclic molecules 3a (3c) and 5a (5c) takes place similarly to that in the parent TMM. Likewise, planar TMMa (TMMc) structures are TSs, while orthogonal ones are true minima. The adiabatic singlet-triplet gaps are also similar, being 14.7 (13.0) and 16.5 (16.2) kcal mol(-1) in the orthogonal (o(1)) and planar TMMa (TMMc), respectively. It has been shown here that the substantial reductions in the ring-opening barriers of MCP derivatives 3a (3c) and 5a (5c) can be largely attributed to ring strain in the former and pi-bond strain in the latter species. PMID- 22316429 TI - Selective dehydration of fructose to 5-hydroxymethylfurfural catalyzed by mesoporous SBA-15-SO(3)H in ionic liquid BmimCl. AB - Mesoporous SBA-15 materials functionalized with propylsulfonic acid groups (SBA 15-SO(3)H) were synthesized through a conventional one-pot route. It was used as a catalyst for the selective synthesis of 5-hydroxymethylfurfural (HMF) from the dehydration of fructose using BmimCl as solvent. Reaction time, temperature and fructose concentration were investigated during the HMF synthesis procedure. The catalyst SBA-15-SO(3)H exhibits high fructose conversion (near 100%) and HMF selectivity (about 81%) with good stability in the HMF synthesis. It was a suitable catalyst to produce HMF from renewable carbohydrates in potential industrial process. PMID- 22316431 TI - Enantioselective synthesis of quaternary alpha-aminophosphonates via conjugate addition of alpha-nitrophosphonates to enones. AB - Enantioselective Michael addition of alpha-nitrophosphonates to enones for the synthesis of alpha-aminophosphonates is reported for the first time. The reaction proceeds in good to high yields and moderate to high selectivity in the presence of a new quinine thiourea catalyst. The quaternary nitrophosphonates were conveniently transformed to cyclic quaternary alpha-aminophosphonates via in situ reduction-intramolecular cyclization or Baeyer-Villiger oxidation followed by in situ reduction-intramolecular cyclization. PMID- 22316432 TI - Low-cost synthesis of flowerlike alpha-Fe2O3 nanostructures for heavy metal ion removal: adsorption property and mechanism. AB - Flowerlike alpha-Fe(2)O(3) nanostructures were synthesized via a template-free microwave-assisted solvothermal method. All chemicals used were low-cost compounds and environmentally benign. These flowerlike alpha-Fe(2)O(3) nanostructures had high surface area and abundant hydroxyl on their surface. When tested as an adsorbent for arsenic and chromium removal, the flowerlike alpha Fe(2)O(3) nanostructures showed excellent adsorption properties. The adsorption mechanism for As(V) and Cr(VI) onto flowerlike alpha-Fe(2)O(3) nanostructures was elucidated by X-ray photoelectron spectroscopy and synchrotron-based X-ray absorption near edge structure analysis. The results suggested that ion exchange between surface hydroxyl groups and As(V) or Cr(VI) species was accounted for by the adsorption. With maximum capacities of 51 and 30 mg g(-1) for As(V) and Cr(VI), respectively, these low-cost flowerlike alpha-Fe(2)O(3) nanostructures are an attractive adsorbent for the removal of As(V) and Cr(VI) from water. PMID- 22316433 TI - Pathogenesis of Korean type 1 (European genotype) porcine reproductive and respiratory syndrome virus in experimentally infected pigs. AB - The aim of this study was to elucidate the pathogenesis of experimental infection with Korean type 1 porcine reproductive and respiratory syndrome virus (PRRSV) by defining the virus distribution, sites of viral replication, viraemia and gross and microscopical lesions in conventional pigs studied for 28 days after intranasal inoculation. Mean rectal temperature was significantly higher in infected pigs than in negative control pigs at 2 days post inoculation (dpi) (P=0.004), 3 dpi (P<0.001), 4 dpi (P=0.003) and 5 dpi (P=0.034). The log(10)TCID(50)/ml of type 1 PRRSV increased significantly at 0-1 dpi (P=0.024) and 5-7 dpi (P=0.029), but decreased at 10-14 dpi (P=0.026) and 14-21 dpi (P=0.012) in infected pigs. Infected pigs developed multifocal, tan-mottled areas of lung tissue with irregular and indistinct borders. Microscopical lesions, when present, were multifocal, mild to moderate, generally most extensive at 5-7 dpi (P=0.036), and were nearly resolved at 28 dpi. Type 1 PRRSV nucleic acid and antigen were detected exclusively within the cytoplasm of macrophages and type I and II pneumocytes. The score for PRRSV-positive cells increased at 3-7 dpi (P<0.05) and decreased at 10-14 dpi (P=0.034) in infected pigs. Thus, respiratory disease was reproduced in conventional pigs by infection with Korean type 1 PRRSV. PMID- 22316434 TI - The Pathological Effects of Melamine and Cyanuric Acid in the Diet of Walking Catfish (Clarius batrachus). AB - The toxicity of melamine and its analogue in man and animals has been reported widely. The aim of the present study was to examine the pathological effects of feeding melamine and cyanuric acid, separately or in combination, to walking catfish (Clarius batrachus). The catfish developed darkening of the skin as early as 3 days post feeding. Melamine-related crystals were distributed multifocally throughout the liver, kidney, heart, spleen and corpuscle of Stannius of fish fed melamine and cyanuric acid in combination. Oil red O staining and electron microscopy revealed that the melamine-related crystals had structure resembling that of plastic polymer crystals. Elevations in the serum concentrations of alanine transaminase, aspartate transaminase, creatinine and uric acid were related to the crystal-associated granulomatous inflammation in the liver and kidney of affected fish. None of the catfish died during the 2-week experiment. Melamine and cyanuric acid are therefore systemically toxic to fish in addition to causing renal crystal formation and renal damage as seen in man and animals. The finding of extrarenal crystals implies that the metabolism and biotransformation of these toxic compounds should be further investigated in aquatic animals. PMID- 22316435 TI - Review article: the extra-skeletal effects of vitamin D in chronic hepatitis C infection. AB - BACKGROUND: Recent interest has focused on the extra-skeletal effects of vitamin D, in particular, in patients with chronic hepatitis C. AIMS: To review data in the literature regarding the extra-skeletal effects of vitamin D in patients with chronic hepatitis C, with and without liver transplantation. METHODS: A Medline search was performed for relevant studies up to August 2011 using the terms 'vitamin D' 'chronic liver disease' and 'hepatitis C'. RESULTS: Vitamin D deficiency is very frequent before liver transplantation ranging between 51% and 92%, whereas, in the liver transplantation setting, the prevalence of vitamin D deficiency is also high. Severe liver disease may increase the risk of vitamin D deficiency and vice versa, as there may be a relationship between vitamin D deficiency and fibrosis. In patients with chronic hepatitis C and those with recurrent of hepatitis C after liver transplantation, recent clinical data shows that a higher serum vitamin D level is an independent predictor of sustained virological response (SVR) following anti-viral therapy, and that a higher SVR is achieved with vitamin D supplementation. CONCLUSIONS: Larger randomised clinical studies with adequate statistical power are needed to confirm these potentially very important nonskeletal effects of vitamin D in patients with chronic hepatitis C. PMID- 22316437 TI - Gastric volvulus after sleeve gastrectomy for morbid obesity. AB - BACKGROUND: Laparoscopic sleeve gastrectomy in morbid obesity has proved to be a safe and reproducible technique. Sleeve gastrectomy, however, is not free of complications. On the other hand, gastric volvulus is reported in those subjects where, either because of laxity of the gastric anatomical fixations or incorrect position of the stomach, rotation or turning is facilitated. CASE: We report the case of a patient with morbid obesity (Bone mass index / BMI 63 Kg/m2), who in the post-operative period immediately following a sleeve gastrectomy, presented early symptoms of upper gastrointestinal occlusion indicative of gastric volvulus of the gastric sleeve. RESULTS: The patient developed a partial obstruction secondary to a mixed volvulus mechanism (organo-axial and partially mesenteric axial) after sleeve gastrectomy. We performed a laparoscopic antrectomy of the gastric sleeve and then a gastroileal anastomosis, a form of biliopancreatic diversion, with a common channel of 80 cm and alimentary limb of 160 cm). 18 months after, the patient has a BMI of 28 kg/m2 and enjoys a good quality of life. CONCLUSION: Sleeve gastrectomy leaves the stomach with no fixations along the entire greater curvature, which may predispose to volvulus. This complication is a rare finding and not reported to date following this intervention, but still needs to be considered in this type of patient. PMID- 22316436 TI - Quantification of hypercoagulable state after blunt trauma: microparticle and thrombin generation are increased relative to injury severity, while standard markers are not. AB - BACKGROUND: Major trauma is an independent risk factor for developing venous thromboembolism. While increases in thrombin generation and/or procoagulant microparticles have been detected in other patient groups at greater risk for venous thromboembolism, such as cancer or coronary artery disease, this association has yet to be documented in trauma patients. This pilot study was designed to characterize and quantify thrombin generation and plasma microparticles in individuals early after traumatic injury. METHODS: Blood was collected in the trauma bay from 52 blunt injured patients (cases) and 19 uninjured outpatients (controls) and processed to platelet poor plasma to allow for (1) isolation of microparticles for identification and quantification by flow cytometry, and (2) in vitro thrombin generation as measured by calibrated automatic thrombography. Data collected are expressed as either mean +/- standard deviation or median with interquartile range. RESULTS: Among the cases, which included 39 men and 13 women (age, 40 +/- 17 years), the injury severity score was 13 +/- 11, the international normalized ratio was 1.0 +/- 0.1, the thromboplastin time was 25 +/- 3 seconds, and platelet count was 238 +/- 62 (thousands). The numbers of total (cell type not specified) procoagulant microparticles, as measured by Annexin V staining, were increased compared to nontrauma controls (541 +/- 139/MUL and 155 +/- 148/MUL, respectively; P < .001). There was no significant difference in the amount of thrombin generated in trauma patients compared to controls; however, peak thrombin was correlated to injury severity (Spearman correlation coefficient R, 0.35; P = .02). CONCLUSION: Patients with blunt trauma have greater numbers of circulating procoagulant microparticles and increased in vitro thrombin generation. Future studies to characterize the cell-specific profiles of microparticles and changes in thrombin generation kinetics after traumatic injury will determine whether microparticles contribute to the hypercoagulable state observed after injury. PMID- 22316438 TI - Effects of ileal interposition on glucose metabolism in obese rats with diabetes. AB - BACKGROUND: Ileal interposition (IT), in which the distal ileum is transposed isoperistaltically into the proximal jejunum, is considered as a procedure for metabolic or antidiabetes surgery. Our aim was to study the effects of IT on glycemic control, fat metabolism, and hormonal changes in obese rats with spontaneous diabetes. METHODS: Animals were divided into either an IT or a sham (SH) group. They underwent an oral glucose tolerance test (OGTT) before and 4 and 8 weeks after the operation. All animals were killed 10 weeks after operation for analyses of tissue weight (liver, pancreas, epididymal fat, brown fat), immunoblotting of uncoupling protein-1 (UCP1) protein in brown adipose tissue (BAT), and fasting plasma levels of glucose, insulin, glucagon-like peptide (GLP) 1, peptide YY (PYY), glucose-dependent insulinotropic polypeptide (GIP), and leptin. RESULTS: Body weight increased postoperatively in both groups compared with preoperative weight, but it did not differ between the 2 groups. Eight weeks postoperatively, integrated blood glucose levels during the OGTT were decreased in IT compared with SH (P < .05). Fasting plasma levels of insulin, GLP-1, and GIP did not differ between the 2 groups, but PYY levels were higher in the IT animals (P < .01). The weight of epididymal and BATs, homeostasis model assessment insulin resistance, and fasting plasma leptin levels were decreased in the IT group (P < .05). Expression of UCP1 was higher in IT than SH animals (P < .05). CONCLUSION: These results suggest that IT improves glucose and lipid metabolism by decreasing insulin resistance and epididymal fat, and increased expression of UCP1 in BAT might be among the mechanisms responsible. PMID- 22316439 TI - The role of liver resection for colorectal cancer metastases in an era of multimodality treatment: a systematic review. AB - BACKGROUND: To determine the role of liver resection in patients with liver and extrahepatic colorectal cancer metastases and the role of chemotherapy in patients in conjunction with liver resection. METHODS: MEDLINE and EMBASE databases were searched for articles published between 1995 and 2010, along with hand searching. RESULTS: A total of 4875 articles were identified, and 83 were retained for inclusion. Meta-analysis was not performed because of heterogeneity and poor quality of the evidence. Outcomes in patients who had liver and lung metastases, liver and portal node metastases, and liver and other extrahepatic disease were reported in 14, 10, and 14 studies, respectively. The role of perioperative chemotherapy was assessed in 30 studies, including 1 randomized controlled trial and 1 pooled analysis. Ten studies assessed the role of chemotherapy in patients with initially unresectable disease, and 5 studies assessed the need for operation after a radiologic complete response. CONCLUSION: The review suggests that: (1) select patients with pulmonary and hepatic CRC metastases may benefit from resection; (2) perioperative chemotherapy may improve outcome in patients undergoing a liver resection; (3) patients whose CRC liver metastases are initially unresectable may benefit from chemotherapy to identify a subgroup who may benefit later from resection; (4) after radiographic complete response (RCR), lesions should be resected if possible. PMID- 22316440 TI - RhoB controls endothelial cell morphogenesis in part via negative regulation of RhoA. AB - Recent studies have suggested a role for the small GTPase RhoB in the control of processes required for angiogenesis. However, the mechanisms whereby RhoB exerts control over these processes are not well understood. Given the role of vascular endothelial growth factor (VEGF) in pathological angiogenesis, we were interested in examining whether RhoB contributed to VEGF-induced angiogenic processes. To assess this, RhoB was specifically depleted in human umbilical vein endothelial cells (HUVEC), using siRNA-targeted strategies. The effects of RhoB depletion on VEGF-induced angiogenic activities were assessed using a variety of standard in vitro angiogenesis assays to assess endothelial cell viability, migration and capillary morphogenesis. Effects of RhoB depletion on signaling from other Rho family member proteins was also assessed using specific activity assays for RhoA and RhoC. We observed that although RhoB appeared dispensable for HUVEC viability, RhoB was required for endothelial cell migration, sprouting, and capillary morphogenesis. We also observed that siRNA-mediated depletion of RhoB in HUVEC resulted in increased RhoA activation in response to VEGF stimulation. This increased RhoA activation contributed to the cellular morphogenesis defects observed in RhoB-depleted cells, as inhibition of RhoA activity using C3 transferase, or inhibition of the activity of the downstream RhoA effectors Rho dependent kinases I and II (ROCK I and II) led to a partial restoration of capillary morphogenesis in the absence of RhoB. Thus our data indicate that RhoB plays a significant role in VEGF-induced endothelial cell morphogenesis in part by negatively regulating the activity of RhoA and the RhoA/ROCK pathway. PMID- 22316441 TI - Protective factors and predictors of vulnerability to chronic stress: a comparative study of 4 communities after 7 years of continuous rocket fire. AB - Many communities across the world are chronically exposed to extreme violence. Responses of residents from a city and rural community in Southern Israel, both exposed to 7 years of daily mortar fire, were compared to residents from demographically, socio-economically and geographically comparable non-exposed control samples to examine protective factors and predictors of vulnerability to chronic war-related attacks. Samples from a highly exposed city (Sderot) and a highly exposed rural community region (Otef Aza), along with a demographically comparable comparison non-exposed city (Ofakim) and non-exposed rural community region (Hevel Lachish), were obtained in 2007 using Random Digit Dialing. In total, 740 individuals (81.8% participation rate) were interviewed about trauma exposure, mental health, functioning and health care utilization. In the highly exposed city of Sderot, 97.8% of residents had been in close proximity to falling rockets; in the highly exposed rural community region of Otef Aza, 95.5% were similarly exposed. Despite exposure to chronic rocket attacks, residents of Otef Aza evidenced little symptomatology: only one person (1.5%) reported symptoms consistent with probable posttraumatic stress disorder (PTSD) and functioning levels did not differ from those of non-exposed communities. In contrast, posttraumatic stress (PTS), distress, functional impairment and health care utilization were substantially higher in the highly exposed city of Sderot than the other three communities. Lack of resources was associated with increased vulnerability among city residents; predictors of PTS across all samples included being female, older, directly exposed to rockets, history of trauma, suffering economic loss, and lacking social support. Increased community solidarity, sense of belonging and confidence in authorities may have served a protective function for residents of rural communities, despite the chronic attacks to which they were exposed. PMID- 22316442 TI - The emerging threat of untreatable gonococcal infection. PMID- 22316443 TI - Antenatal thyroid screening and childhood cognitive function. AB - BACKGROUND: Children born to women with low thyroid hormone levels have been reported to have decreased cognitive function. METHODS: We conducted a randomized trial in which pregnant women at a gestation of 15 weeks 6 days or less provided blood samples for measurement of thyrotropin and free thyroxine (T(4)). Women were assigned to a screening group (in which measurements were obtained immediately) or a control group (in which serum was stored and measurements were obtained shortly after delivery). Thyrotropin levels above the 97.5th percentile, free T(4) levels below the 2.5th percentile, or both were considered a positive screening result. Women with positive findings in the screening group were assigned to 150 MUg of levothyroxine per day. The primary outcome was IQ at 3 years of age in children of women with positive results, as measured by psychologists who were unaware of the group assignments. RESULTS: Of 21,846 women who provided blood samples (at a median gestational age of 12 weeks 3 days), 390 women in the screening group and 404 in the control group tested positive. The median gestational age at the start of levothyroxine treatment was 13 weeks 3 days; treatment was adjusted as needed to achieve a target thyrotropin level of 0.1 to 1.0 mIU per liter. Among the children of women with positive results, the mean IQ scores were 99.2 and 100.0 in the screening and control groups, respectively (difference, 0.8; 95% confidence interval [CI], -1.1 to 2.6; P=0.40 by intention-to-treat analysis); the proportions of children with an IQ of less than 85 were 12.1% in the screening group and 14.1% in the control group (difference, 2.1 percentage points; 95% CI, -2.6 to 6.7; P=0.39). An on-treatment analysis showed similar results. CONCLUSIONS: Antenatal screening (at a median gestational age of 12 weeks 3 days) and maternal treatment for hypothyroidism did not result in improved cognitive function in children at 3 years of age. (Funded by the Wellcome Trust UK and Compagnia di San Paulo, Turin; Current Controlled Trials number, ISRCTN46178175.). PMID- 22316444 TI - Memory enhancement and deep-brain stimulation of the entorhinal area. AB - BACKGROUND: The medial temporal structures, including the hippocampus and the entorhinal cortex, are critical for the ability to transform daily experience into lasting memories. We tested the hypothesis that deep-brain stimulation of the hippocampus or entorhinal cortex alters memory performance. METHODS: We implanted intracranial depth electrodes in seven subjects to identify seizure onset zones for subsequent epilepsy surgery. The subjects completed a spatial learning task during which they learned destinations within virtual environments. During half the learning trials, focal electrical stimulation was given below the threshold that elicits an afterdischarge (i.e., a neuronal discharge that occurs after termination of the stimulus). RESULTS: Entorhinal stimulation applied while the subjects learned locations of landmarks enhanced their subsequent memory of these locations: the subjects reached these landmarks more quickly and by shorter routes, as compared with locations learned without stimulation. Entorhinal stimulation also resulted in a resetting of the phase of the theta rhythm, as shown on the hippocampal electroencephalogram. Direct hippocampal stimulation was not effective. In this small series, no adverse events associated with the procedure were observed. CONCLUSIONS: Stimulation of the entorhinal region enhanced memory of spatial information when applied during learning. (Funded by the National Institutes of Health and the Dana Foundation.). PMID- 22316445 TI - Tai chi and postural stability in patients with Parkinson's disease. AB - BACKGROUND: Patients with Parkinson's disease have substantially impaired balance, leading to diminished functional ability and an increased risk of falling. Although exercise is routinely encouraged by health care providers, few programs have been proven effective. METHODS: We conducted a randomized, controlled trial to determine whether a tailored tai chi program could improve postural control in patients with idiopathic Parkinson's disease. We randomly assigned 195 patients with stage 1 to 4 disease on the Hoehn and Yahr staging scale (which ranges from 1 to 5, with higher stages indicating more severe disease) to one of three groups: tai chi, resistance training, or stretching. The patients participated in 60-minute exercise sessions twice weekly for 24 weeks. The primary outcomes were changes from baseline in the limits-of-stability test (maximum excursion and directional control; range, 0 to 100%). Secondary outcomes included measures of gait and strength, scores on functional-reach and timed up and-go tests, motor scores on the Unified Parkinson's Disease Rating Scale, and number of falls. RESULTS: The tai chi group performed consistently better than the resistance-training and stretching groups in maximum excursion (between-group difference in the change from baseline, 5.55 percentage points; 95% confidence interval [CI], 1.12 to 9.97; and 11.98 percentage points; 95% CI, 7.21 to 16.74, respectively) and in directional control (10.45 percentage points; 95% CI, 3.89 to 17.00; and 11.38 percentage points; 95% CI, 5.50 to 17.27, respectively). The tai chi group also performed better than the stretching group in all secondary outcomes and outperformed the resistance-training group in stride length and functional reach. Tai chi lowered the incidence of falls as compared with stretching but not as compared with resistance training. The effects of tai chi training were maintained at 3 months after the intervention. No serious adverse events were observed. CONCLUSIONS: Tai chi training appears to reduce balance impairments in patients with mild-to-moderate Parkinson's disease, with additional benefits of improved functional capacity and reduced falls. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00611481.). PMID- 22316447 TI - IgG4-related disease. PMID- 22316446 TI - Sources of regional variation in Medicare Part D drug spending. AB - BACKGROUND: Sources of regional variation in spending for prescription drugs under Medicare Part D are poorly understood, and such variation may reflect differences in health status, use of effective treatments, or selection of branded drugs over lower-cost generics. METHODS: We analyzed 2008 Medicare data for 4.7 million beneficiaries for prescription-drug use and expenditures overall and in three drug categories: angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs), 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins), and selective serotonin-reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Differences in per capita expenditures across hospital-referral regions (HRRs) were decomposed into annual prescription volume and cost per prescription. The ratio of prescriptions filled as branded drugs to all prescriptions filled was calculated. We adjusted all measures for demographic, socioeconomic, and health-status differences. RESULTS: Mean adjusted per capita pharmaceutical spending ranged from $2,413 in the lowest to $3,008 in the highest quintile of HRRs. Most (75.9%) of that difference was attributable to the cost per prescription ($53 vs. $63). Regional differences in cost per prescription explained 87.5% of expenditure variation for ACE inhibitors and ARBs and 56.3% for statins but only 36.1% for SSRIs and SNRIs. The ratio of branded-drug to total prescriptions, which correlated highly with cost per prescription, ranged across HRRs from 0.24 to 0.45 overall and from 0.24 to 0.55 for ACE inhibitors and ARBs, 0.29 to 0.60 for statins, and 0.15 to 0.51 for SSRIs and SNRIs. CONCLUSIONS: Regional variation in Medicare Part D spending results largely from differences in the cost of drugs selected rather than prescription volume. A reduction in branded-drug use in some regions through modification of Part D plan benefits might lower costs without reducing quality of care. (Funded by the National Institute on Aging and others.). PMID- 22316448 TI - Images in clinical medicine. Deep sulcus sign. PMID- 22316449 TI - Case records of the Massachusetts General Hospital. Case 4-2012. A 37-year-old man with muscle pain, weakness, and weight loss. PMID- 22316450 TI - The debate over thyroid-function screening in pregnancy. PMID- 22316451 TI - Brain stimulation, learning, and memory. PMID- 22316453 TI - Gene therapy meets stem cells. PMID- 22316455 TI - Budesonide in preschool-age children with recurrent wheezing. PMID- 22316456 TI - Budesonide in preschool-age children with recurrent wheezing. PMID- 22316457 TI - Budesonide in preschool-age children with recurrent wheezing. PMID- 22316459 TI - Mycophenolate or azathioprine maintenance in lupus nephritis. PMID- 22316460 TI - Mycophenolate or azathioprine maintenance in lupus nephritis. PMID- 22316462 TI - Systemic lupus erythematosus. PMID- 22316463 TI - Systemic lupus erythematosus. PMID- 22316465 TI - Extracorporeal membrane oxygenation for ARDS in adults. PMID- 22316466 TI - Extracorporeal membrane oxygenation for ARDS in adults. PMID- 22316467 TI - Extracorporeal membrane oxygenation for ARDS in adults. PMID- 22316468 TI - Relationship between cerebrospinal fluid glucose and serum glucose. PMID- 22316469 TI - Images in clinical medicine. Pyogenic granuloma of the finger. PMID- 22316470 TI - Interactive medical case. A startling decline. PMID- 22316479 TI - Immunophenotyping of classic murine myeloma cell lines used for monoclonal antibody production. AB - Murine myeloma cell lines play an important role in different areas of scientific research and are essential tools for monoclonal antibody production technology. Thus, it is important to understand the biology of these cell lines in order to provide useful information to various research fronts. The present study aims to perform detailed analyses of surface antigens expressed on three major murine myeloma cell lines extensively used for MAb production. The P3X63Ag8.653 cell line expresses molecules associated with T cell interaction (CD40(low), CD80(low)), as well as antigens related to plasma cell phenotype (CD138(high), CD184(low)). The Sp2/0-Ag14 cell line presents molecules associated with BCR activation and regulation (CD79b(low), CD22(low), CD72(med)), molecules related to T cell interaction (CD40(low), CD80(low)), and markers of plasma cell phenotype (CD138(high), CD184(low)). The NS1 cell line presents all molecules of plasma cell phenotype evaluated in this study (CD184(low), CD138(high), CD38(med)) with low expression of CD72 (CD72(low)), a molecule related to BCR activation. Molecules associated with immune response modulation such as CD23 and CD25, as well as CD117, a marker related to undifferentiated cell phenotype, were not observed in any of the three murine myeloma cell lines evaluated. These data show that in spite of their common origin and function, the immunological profiles differ between P3X63Ag8.653, Sp2/0-Ag14, and NS1 cell lines. PMID- 22316480 TI - Several commercially available anti-CCR5 monoclonal antibodies lack specificity and should be used with caution. AB - CCR5 (CD195) is a receptor for the chemokines RANTES, MIP-1alpha, and MIP-1beta and is used by HIV-1 as a co-receptor for entry into macrophages and CD4+ T cells. CCR5 exists in multiple conformations in the membrane and is present at low levels on human macrophages, making it difficult to detect. Nine commercially available anti-CCR5 monoclonal antibodies were evaluated for their specificity and their recognition of CCR5 expressed by macrophages. Unexpectedly, we found that three of the nine clones tested displayed substantial background binding to CCR5 negative cells, suggesting that these antibodies may give unreliable results. We recommend the use of clones CTC8, 45531 (PE conjugated), and 45523 and advise that data obtained using CTC5, 45531 (unconjugated), and 45549 anti CCR5 antibody clones should be interpreted with care. PMID- 22316481 TI - Monoclonal antibodies from Rubia cordifolia against antitumor cyclohexapeptide deoxybouvardin and their use in immunoassay. AB - An immunoassay system was established for the estimation of the quantity of an antitumor cyclohexapeptide, deoxybouvardin (RA-V) from Bouvardia ternifolia (Cav.) Schlecht, Rubia cordifolia L., and R. akane Nakai (Rubiaceae). First, RA-V was converted into a protein conjugate to make it an effective antigen. In the conjugate the molecular ratio between RA-V and the carrier protein was 5.9:1. The splenocytes from the mouse immunized with the conjugate were then fused with mouse myeloma cells to produce hybridoma, secreting monoclonal antibodies (MAbs) against RA-V. Two clones were isolated, one producing MAb IgG(1) and the other MAb IgG(2b), both having a kappa light chain. The resultant MAbs were evaluated for their sensitivity and cross-reactivity. PMID- 22316482 TI - Monoclonal antibodies against the Escherichia coli DNA repair protein RadA/Sms. AB - The RadA/Sms protein facilitates DNA repair in Escherichia coli cells damaged by UV radiation, X-rays, and chemical agents. However, the precise mechanism by which RadA/Sms aids DNA repair is unknown. Here we report the production of monoclonal antibodies (MAbs) specific for RadA/Sms for use in biochemical and physiological investigations. Histidine-tagged RadA/Sms (RadA-6xHis) was overproduced in E. coli BL21 cells transformed with the radA/sms coding region in plasmid pRSET A and purified by nickel affinity chromatography. Splenocytes from female BALB/c mice hyperimmunized with the purified protein were fused to SP2/0 Ag14 myeloma cells, and the resultant hybridomas were selected in HAT medium. MAbs were detected in hybridoma culture supernatants by indirect ELISA and Western blot analysis against purified RadA-6xHis. MAbs from four cell lines were further evaluated by Western blotting against peptide maps generated by endoproteinase Glu-C digestion of RadA-6xHis. Each of the four MAbs recognized a unique epitope on the fusion protein. Two of the MAbs (6F5 and 2A2) also detected wild-type (tagless) RadA/Sms produced from the pJS003 plasmid in E. coli K-12 cells. We anticipate that these antibodies will prove useful for the detection, isolation, and functional analysis of RadA/Sms. PMID- 22316483 TI - Chitinase 3-like 2 protein monoclonal antibodies. AB - Chitinase 3-like 2 (CHI3L2) is one of the most overexpressed genes in glioblastoma. Despite this, both the CHI3L2 gene and its protein product CHI3L2 are poorly characterized. Here we report the generation and characterization of monoclonal antibodies to CHI3L2 protein (CHI3L2 MAbs). Bacterially expressed 6 His-tagged full-length CHI3L2 was used as antigen. Spleen cells from immunized mice were collected and fused with SP2/0 myeloma cells. Hybridoma clones 2D3 and 4D2 producing high titer CHI3L2 MAbs were identified by enzyme-linked immunosorbent assay (ELISA) and further examined for their activity with the CHI3L2 protein by Western blot analysis and immunoprecipitation. The 2D3 clone was chosen for mouse inoculation and ascites formation. Antibodies derived from the ascitic fluid specifically recognized the recombinant CHI3L2 protein and strongly interacted with CHI3L2 in glioblastoma tissue lysate, as determined by Western blot analysis. The antibodies generated may be useful as a tool in various aspects of CHI3L2 investigation. PMID- 22316484 TI - Antibodies against B7-DC with differential binding properties exert opposite effects. AB - Programmed cell death 1 (PD-1) is an immunoregulatory receptor on T cells that binds two ligands, B7-H1 and B7-DC. Although accumulating reports suggest a critical role for the B7-H1:PD-1 pathway in peripheral tolerance, the actual involvement of B7-DC has not been well confirmed. Here, we established a new MAb against mouse B7-DC (MIH37) and compared its functional properties with a previously established anti-B7-DC MAb (TY25). Binding analyses using flow cytometry demonstrated that MIH37 showed an approximately four-fold higher binding affinity to B7-DC and stronger inhibitory effects on B7-DC:PD-1 binding. In contrast to the effects of TY25, treatment with MIH37 at both sensitization and challenge inhibited hapten-induced contact hypersensitivity reactions. Furthermore, the addition of MIH37 inhibited OVA-specific T cell responses in vitro. The inhibitory effects of MIH37 were counteracted by co-blockade with PD-1 and absent in PD-1-deficient mice, suggesting PD-1-dependent action of MIH37. Our present results suggest that greater complexities of PD-1-mediated functions are induced via ligand binding for controlling immunity and tolerance. PMID- 22316485 TI - Development of novel mouse hybridomas producing monoclonal antibodies specific to human and mouse nucleolar protein SURF-6. AB - SURF-6 is an evolutionarily conserved nucleolar protein that is important for cell viability; however, its function in mammals still remains uncertain. The aim of this study is to generate monoclonal antibodies to human SURF-6 protein suitable for fundamental and biomedical research. The full-size human SURF-6 was expressed as a recombinant GST-fusion protein and used as an antigen to generate monoclonal antibodies, S79 and S148, specific for SURF-6. The monoclonal antibody produced by hybridoma clone S79 specifically recognizes endogenous SURF-6 by Western and immunofluorescence analyses in various cultured human cells, and by immunohistochemistry in paraffin-embedded sections of human breast cancer samples. Moreover, S79 immunoprecipitates protein complexes containing SURF-6 from HeLa cells extracts. The antibody S79 recognizes SURF-6 only in human cells; however, the antibody produced by hybridoma clone S148 can detect SURF-6 of human and mouse origin. Monoclonal antibodies to the nucleolar protein SURF-6 described in this work can be a useful tool for studies of ribosome biogenesis in normal and cancer cells. PMID- 22316486 TI - Characterization and application of monoclonal antibody against hepatitis C virus nonstructual protein three. AB - Developing assays for detecting HCV antigens could be beneficial because viral proteins appear earlier than antibodies and are more stable than RNA in the serum. Monoclonal antibody was prepared by immunization and cell fusion. Subclass, specificity, and efficiency of monoclonal antibodies were determined by ELISA. Epitope specificity of monoclonal antibodies was analyzed by ELISA additivity test. HCV antigen in serum of hepatitis patients was examined by double monoclonal antibody sandwich ELISA. Five hybridoma cell lines were screened and named HCV(1), HCV(2), HCV(3), HCV(4), and HCV(5). These five monoclonal antibodies had high specificity and efficiency. The additivity test showed that HCV(2), HCV(4), and HCV(5) recognized different epitopes, which can be matched in ELISA. Of 173 anti-HCV positive patients, 37 (21.4%) were positive for HCV antigen. Of 1498 anti-HCV negative patients, 10 (0.67%) were positive for HCV antigen. Fifty normal controls were negative for HCV antigen. HCV antigen detection had moderate agreement and correlation with HCV RNA detection (kappa=0.577, p<0.01; r=0.59, p<0.01). This result indicates that the monoclonal antibody against HCV NS(3) may be a potential diagnostic reagent, which would provide a foundation for developing a sandwich ELISA of HCV antigen detection. PMID- 22316487 TI - Monoclonal antibody that blocks the Toll-like receptor 5 binding region of flagellin. AB - The conserved domain of bacteria-derived flagellin coupling Toll-like receptor 5 (TLR5) activates NF-kappaB and MAPK signaling transductions, which subsequently regulate the transcription and expression of genes encoding immune mediators. However, whether the flagellin binding monoclonal antibody (MAb) obstructs TLR5 associated signaling is unclear. Here we report on the production and characterization of MAb 5G10 that specifically recognizes flagellin. The MAb 5G10 was produced by the hybridization of mouse myeloma cell SP2/0 with splenocyte from a flagellin immunized BALB/c mouse. We observed that deletion of the conserved amino acid residues 89-96 made flagellin lose its capacity for binding 5G10. Additionally, MAb 5G10 remarkably suppressed the expression of cytokine IL8 of Caco-2 cell by blocking the flagellin-TLR5 signaling. Furthermore, this MAb would be useful for cytosolic localization of flagellin and would facilitate the elucidation of the physiological function of specific pathogen-associated molecular patterns. PMID- 22316488 TI - Purification of anti-Japanese encephalitis virus monoclonal antibody by ceramic hydroxyapatite chromatography without proteins A and G. AB - Antibody purification using proteins A and G has been a standard method for research and industrial processes. The conventional method, however, includes a three-step process, including buffer exchange, before chromatography. In addition, proteins A and G require low pH elution, which causes antibody aggregation and inactivates the antibody's immunity. This report proposes a two step method using hydroxyapatite chromatography and membrane filtration, without proteins A and G. This novel method shortens the running time to one-third the conventional method for each cycle. Using our two-step method, 90.2% of the monoclonal antibodies purified were recovered in the elution fraction, the purity achieved was >90%, and most of the antigen-specific activity was retained. This report suggests that the two-step method using hydroxyapatite chromatography and membrane filtration should be considered as an alternative to purification using proteins A and G. PMID- 22316494 TI - Identification of novel miR-21 target proteins in multiple myeloma cells by quantitative proteomics. AB - Substantial evidence indicates that microRNA-21 (miR-21) is a key oncomiR in carcinogenesis and is significantly elevated in multiple myeloma (MM). In this study, we explored the role of miR-21 in human MM cells and searched for miR-21 targets. By knocking down the expression of endogenous miR-21 in U266 myeloma cells, we observed reduced growth, an arrested cell cycle, and increased apoptosis. To further understand its molecular mechanism in the pathogenesis of MM, we employed a SILAC (stable isotope labeling by amino acids in cell culture) based quantitative proteomic strategy to systematically identify potential targets of miR-21. In total, we found that the expression of 178 proteins was up regulated significantly by miR-21 inhibition, implying that they could be potential targets of miR-21. Among these, the protein inhibitor of activated STAT3 (PIAS3) was confirmed as a direct miR-21 target by Western blotting and reporter gene assays. We further demonstrated that miR-21 enhances the STAT3 dependent signal pathway by inhibiting the function of PIAS3 and that down regulation of PIAS3 contributes to the oncogenic function of miR-21. This elucidation of the role of PIAS3 in the miR-21-STAT3 positive regulatory loop not only may shed light on the molecular basis of the biological effects of miR-21 observed in MM cells but also has direct implications for the development of novel anti-MM therapeutic strategies. PMID- 22316495 TI - Percutaneous retrieval of coiled double-J stent from renal pelvis after Anderson Hynes pyeloplasty: report of two cases. AB - Double-J (DJ) ureteral stents are routinely placed for internal urinary diversion post renal pyeloplasty. Malfunction of the stent may occur due to migration, necessitating removal. Upward migration of a DJ stent is rarely encountered in urologic practice when a ureteroscope is used to retrieve the stent. However, retrieval of upwardly migrated stents through ureteroscopy may be challenging in the pediatric population, especially in postoperative cases. We report two pediatric cases of post Anderson-Hynes pyeloplasty in whom the DJ stents were found coiled up in the renal pelvis and were retrieved successfully through percutaneous nephrostomy using semirigid bronchoscopic forceps. PMID- 22316496 TI - Fetal acetylcholine receptor inactivation syndrome and maternal myasthenia gravis: a case report. AB - Fetal acetylcholine receptor inactivation syndrome is a rare condition occurring in newborns of myasthenic mothers, characterized by bulbar and facial weakness after recovery from the generalized muscle weakness. Antibodies against fetal subunit of acetylcholine receptor seem to have a pathogenetic role leading to long-lasting injury in vulnerable muscle groups. We report a girl, born to a myasthenic mother, who presented with this peculiar phenotype associated with high titers of antibodies specific to the fetal acetylcholine receptor. Although the infant had partial clinical improvement she died prematurely of aspiration pneumonia. We believe that this is a rare but possibly unrecognized condition that should be considered in newborns with persistent myasthenic features even in asymptomatic mothers, and clinicians should consider supportive intervention to avoid fatal complications. PMID- 22316497 TI - Transition to early parenthood, and family functioning relationships in Japan: a longitudinal study. AB - Greater knowledge of the process by which postpartum parents acquire further awareness of their child and fulfill parental roles will likely lead to an understanding that creates a new approach to nursing. This study explored the transition to parenthood and the relationship between parenthood and family functioning in first-time mothers and fathers. Seventy-eight parents (41 mothers, 37 fathers) participated in the study and completed the Scale of Early Childrearing Parenthood and Family Assessment Inventory at birth and at 1, 3, 6, and 12 months postpartum. The levels of parental role attainment and awareness of the child rose dramatically between birth and 3 months postpartum, thereafter stabilizing up to 12 months postpartum. Parenthood and family functioning showed a moderately positive correlation, which gradually became more positive over time. Appropriate nursing interventions might be necessary for parents who show difficulty in accepting their parental roles and have low levels of awareness of their child after 3 months postpartum. Such intervention might be necessary for not only the parents, but also the family unit. PMID- 22316498 TI - Iterative reconstruction methods in X-ray CT. AB - Iterative reconstruction (IR) methods have recently re-emerged in transmission x ray computed tomography (CT). They were successfully used in the early years of CT, but given up when the amount of measured data increased because of the higher computational demands of IR compared to analytical methods. The availability of large computational capacities in normal workstations and the ongoing efforts towards lower doses in CT have changed the situation; IR has become a hot topic for all major vendors of clinical CT systems in the past 5 years. This review strives to provide information on IR methods and aims at interested physicists and physicians already active in the field of CT. We give an overview on the terminology used and an introduction to the most important algorithmic concepts including references for further reading. As a practical example, details on a model-based iterative reconstruction algorithm implemented on a modern graphics adapter (GPU) are presented, followed by application examples for several dedicated CT scanners in order to demonstrate the performance and potential of iterative reconstruction methods. Finally, some general thoughts regarding the advantages and disadvantages of IR methods as well as open points for research in this field are discussed. PMID- 22316499 TI - Implications of central immune signaling caused by drugs of abuse: mechanisms, mediators and new therapeutic approaches for prediction and treatment of drug dependence. AB - In the past two decades a trickle of manuscripts examining the non-neuronal central nervous system immune consequences of the drugs of abuse has now swollen to a significant body of work. Initially, these studies reported associative evidence of central nervous system proinflammation resulting from exposure to the drugs of abuse demonstrating key implications for neurotoxicity and disease progression associated with, for example, HIV infection. However, more recently this drug-induced activation of central immune signaling is now understood to contribute substantially to the pharmacodynamic actions of the drugs of abuse, by enhancing the engagement of classical mesolimbic dopamine reward pathways and withdrawal centers. This review will highlight the key in vivo animal, human, biological and molecular evidence of these central immune signaling actions of opioids, alcohol, cocaine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA). Excitingly, this new appreciation of central immune signaling activity of drugs of abuse provides novel therapeutic interventions and opportunities to identify 'at risk' individuals through the use of immunogenetics. Discussion will also cover the evidence of modulation of this signaling by existing clinical and pre-clinical drug candidates, and novel pharmacological targets. Finally, following examination of the breadth of central immune signaling actions of the drugs of abuse highlighted here, the current known common immune signaling components will be outlined and their impact on established addiction neurocircuitry discussed, thereby synthesizing a common neuroimmune hypothesis of addiction. PMID- 22316501 TI - Evaluating the cost effectiveness of donepezil in the treatment of Alzheimer's disease in Germany using discrete event simulation. AB - BACKGROUND: Previous cost-effectiveness studies of cholinesterase inhibitors have modeled Alzheimer's disease (AD) progression and treatment effects through single or global severity measures, or progression to "Full Time Care". This analysis evaluates the cost-effectiveness of donepezil versus memantine or no treatment in Germany by considering correlated changes in cognition, behavior and function. METHODS: Rates of change were modeled using trial and registry-based patient level data. A discrete event simulation projected outcomes for three identical patient groups: donepezil 10 mg, memantine 20 mg and no therapy. Patient mix, mortality and costs were developed using Germany-specific sources. RESULTS: Treatment of patients with mild to moderately severe AD with donepezil compared to no treatment was associated with 0.13 QALYs gained per patient, and 0.01 QALYs gained per caregiver and resulted in average savings of ?7,007 and ?9,893 per patient from the healthcare system and societal perspectives, respectively. In patients with moderate to moderately-severe AD, donepezil compared to memantine resulted in QALY gains averaging 0.01 per patient, and savings averaging ?1,960 and ?2,825 from the healthcare system and societal perspective, respectively.In probabilistic sensitivity analyses, donepezil dominated no treatment in most replications and memantine in over 70% of the replications. Donepezil leads to savings in 95% of replications versus memantine. CONCLUSIONS: Donepezil is highly cost-effective in patients with AD in Germany, leading to improvements in health outcomes and substantial savings compared to no treatment. This holds across a variety of sensitivity analyses. PMID- 22316502 TI - Effect of Sanguisorba officinalis L on breast cancer growth and angiogenesis. AB - OBJECTIVE: Sanguisorba officinalis L. (SA) has shown anti-inflammation, hematopoiesis and immunity enhancing properties. No detailed studies have been reported on its anti-cancer effects. This study therefore was undertaken to analyze its effects on human breast cancer utilizing in vitro and in vivo methodologies. METHODS: Human breast cancer cell lines MCF-7 and MDA-MB-231 were utilized for evaluating SA influences on tumor progression and angiogenesis processes like proliferation, the cell cycle, apoptosis, tube formation and migration abilities. Both cancer xenografts were also used to determine the herb efficacy in vivo. Bioactivity-guided fractionation was carried out to determine the bioactive compounds in SA. RESULTS: SA inhibited proliferation, induced S phase arrest and triggered mitochondrial pathway apoptosis in both cancer cells. Angiogenesis experiments revealed that SA inhibited VEGF expression in both cancer cell lines. Meanwhile, the proliferation, tube formation and migration abilities of endothelial cells were also inhibited. In vivo experiments demonstrated that SA reduced tumor size and neoangiogenesis in both cancer xenografts. Gallic acid and ellagic acid were finally identified as bioactive compounds in SA. CONCLUSIONS: SA might be of value as a breast cancer preventive and therapeutic agent by inducing apoptosis and inhibiting angiogenesis. Further research is needed to evaluate its metabolism and synergistic effects with chemotherapeutic drugs. PMID- 22316503 TI - Body mass index and the risk of obesity in coeliac disease treated with the gluten-free diet. AB - BACKGROUND: Coeliac disease is increasingly diagnosed and weight changes are common after adoption of a gluten-free diet (GFD), however data on body mass index (BMI) changes are limited. AIM: To assess changes in BMI after diagnosis in a large coeliac population. METHODS: A total of 1018 patients with biopsy confirmed coeliac disease seen at our centre were studied retrospectively. Initial and follow-up BMIs were recorded, as was GFD adherence as assessed by an expert dietitian. RESULTS: A total of 679 patients with at least two recorded BMIs and GFD adherence data were included in the study. Mean follow-up was 39.5 months. Compared to regional population data, the coeliac cohort was significantly less likely to be overweight or obese (32% vs. 59%, P < 0.0001). Mean BMI increased significantly after GFD initiation (24.0 to 24.6; P < 0.001). 21.8% of patients with normal or high BMI at study entry increased their BMI by more than two points. CONCLUSIONS: Individuals with coeliac disease have lower BMI than the regional population at diagnosis. BMI increases on the GFD, especially in those that adhere closely to the GFD. On the GFD, 15.8% of patients move from a normal or low BMI class into an overweight BMI class, and 22% of patients overweight at diagnosis gain weight. These results indicate that weight maintenance counselling should be an integral part of coeliac dietary education. PMID- 22316504 TI - Stereoselective synthesis of cis-2,5-disubstituted THFs: application to adjacent bis-THF cores of Annonaceous acetogenins. AB - The iodocyclization of gamma,delta-unsaturated alcohols in the presence of a silyl enol ether produced cis-2,5-disubstituted tetrahydrofurans in one pot via siloxy intermediates. N-Iodosuccinimide (NIS) effectively worked as an activator of the double bonds in the substrates and the silyl enol ether. Application to an expedient synthesis of the adjacent bis-tetrahydrofuran core of Annonaceous acetogenins with a cis/threo/cis relative stereochemistry is also described. PMID- 22316505 TI - Editorial: Renaming low risk prostate cancer: proceed cautiously. PMID- 22316506 TI - Legends in urology. PMID- 22316507 TI - Contrast-induced nephropathy and nephrogenic systemic fibrosis: minimizing the risk. AB - INTRODUCTION: Contrast-enhanced cross-sectional imaging is essential to the urologist's practice. Traditionally, patients with impaired renal function could not be imaged with a computed tomography (CT) scan with contrast due to the risk of contrast-induced nephropathy (CIN). These patients could alternatively be imaged by magnetic resonance imaging (MRI) with gadolinium. However, the recent identification of the association between nephrogenic systemic fibrosis (NSF) and gadolinium administration has created significant challenges for urologists and radiologists when faced with the need for evaluation with contrast-enhanced cross sectional imaging. In this review, we summarize the most comprehensive articles discussing both NSF and CIN and present a straightforward, evidence-based algorithm to determine the appropriate approach to cross-sectional imaging for all patients, as well as future directions regarding cross-sectional imaging. MATERIALS AND METHODS: A MEDLINE literature search for review articles from 1966 to August 2009 was performed. Selected additional articles for specific topics were also reviewed. This search yielded a total of 25 articles for NSF and 28 for CIN that were reviewed. RESULTS: The pathophysiology and risk factors of NSF and CIN are discussed, as well as potential interventions to decrease either morbidity or incidence. A multidisciplinary (urologist, nephrologist, radiologist) evidence-based algorithm is introduced for managing patients in need of cross-sectional imaging. CONCLUSIONS: The associated risks of contrast enhanced, cross-sectional imaging has created significant challenges for urologic evaluation. We propose an evidence-based approach to guide patient therapy, which can minimize patient risk and physician anxiety, while simplifying the decision making process. PMID- 22316508 TI - Chronic prostatitis-like symptoms in African males aged 16-19 years. AB - INTRODUCTION: To estimate the prevalence of chronic prostatitis (CP)-like symptoms in African adolescents, examining the impact of demographic factors, CP like symptoms (i.e., pain, urinary) and depressive symptoms on quality of life (QoL). MATERIALS AND METHODS: Community dwelling African males aged 16-19 years (M = 16.97; SD = .88; n = 166), attending secondary school participated. CP-like case identification was based on NIH-Chronic Prostatitis Symptom Index definition (NIH-CPSI; pain in perineum and/or with ejaculation and NIH-CPSI total pain score of >= 4 [mild] and >= 8 [moderate-severe]). The Patient Health Questionnaire (PHQ) assessed depressive symptoms. CP-like point prevalence was estimated and multivariable regressions predicted diminished QoL as screened in the NIH-CPSI QoL domain. Participants were consented by field researchers and all potential participants agreed to complete the measures in classroom setting. RESULTS: Prevalence of at least mild CP-like symptoms by NIH-CPSI case identification was 13.3%, with 5.4% of adolescents reporting moderate-severe symptoms. Greater pain, urinary and depressive symptoms and rural setting of school were associated with diminished QoL, and pain (beta = .36) most strongly predicted poorer QoL. CONCLUSIONS: As in North American adults and adolescents, African adolescents report CP-like symptom occurrence with pain associated with lower QoL. The data suggest an adolescent CP syndrome is an internationally important and understudied area for future epidemiological and clinical investigations. PMID- 22316509 TI - Early outcomes of the transobturator male sling based on body mass index. AB - INTRODUCTION: Little is known regarding factors that contribute to the long term success or failure of the transobturator male sling for stress urinary incontinence. The objective of this study was to compare the outcomes of the transobturator male sling for stress urinary incontinence based on body mass index (BMI). MATERIALS AND METHODS: A retrospective review was performed of 31 transobturator male slings placed at a single institution from 2008 to 2010. Success of the procedure was defined as resolution of leakage or great improvement of leakage by the Patient Global Impression of Improvement scale and lack of urinary leakage on postoperative physical exam. Patients were divided into one of three groups: ideal weight (BMI 18.5-24.9 kg/m(2)), overweight (25 29.9 kg/m(2)), and obese (> 30 kg/m(2)). Outcomes and complications were compared between groups. RESULTS: Etiology of urinary incontinence was radical prostatectomy in 28 patients and a transurethral procedure for infection or benign prostatic hypertrophy (BPH) in 3 patients. Successful treatment of incontinence was significantly higher in the ideal weight (7/8 or 88%) and overweight group (13/14 or 93%) in comparison to the obese group (4/9 or 44%), (p = 0.019). Postoperative complications were similar between groups. CONCLUSIONS: Obese patients had lower success rates after transobturator sling in comparison to ideal and overweight patients. We feel this may be due to increased intra abdominal pressure transmission to the bladder, urethra, and sling itself. These patients may be better candidates for an artificial urinary sphincter or should be counseled to undergo pre-preoperative weight loss to improve sling outcomes. PMID- 22316510 TI - Trajectory image-guided percutaneous renal cryoablation in a porcine model: a pilot study. AB - INTRODUCTION: To assess the technical feasibility and safety of trajectory image guided percutaneous renal cryoablation in a porcine model. MATERIALS AND METHODS: Six pigs (12 kidneys) were utilized. Only the posterior and lateral regions of the kidneys were considered. A bone-anchored dynamic reference frame (DRF) was inserted into the iliac crest and the O-Arm and StealthStation TREON System (OASSTS, Medtronic, CO, USA) was used to acquire 3-dimensional (3D) imaging of the kidneys. A hand-held pointing device was crafted from a cryoablation needle (Galil Medical, MN, USA) and an optical reference frame. The hand-held pointer/cryoablation needle ("cryoprobe") was then optically recognized by the OASSTS. The cryoprobe was then used to navigate its tip into a randomly chosen renal region of interest using 3D trajectory images. Two freeze-thaw cryoablation cycles were then performed. We assessed treatment times and effective radiation doses. We also assessed concordance between projected iceball location on trajectory imaging and cryolesion location on necropsy. RESULTS: The mean total treatment time was 24.0 minutes. The mean effective radiation dose was 23.7 mSv per kidney treated. The trajectory-guided images used to place the cryoprobe tips into the renal region of interest agreed with the necropsy-determined location of the cryolesion in all cases. Injury to a lumbar muscle and a renal pelvis were observed in two separate cases, respectively. CONCLUSIONS: Trajectory image guided percutaneous renal cryoablation using OASSTS is technically feasible, appears safe, and is associated with acceptable levels of radiation exposure. Comparison of trajectory image-guidance and cryolesions on necropsy demonstrated concordant needle placement. PMID- 22316511 TI - IPSS quality of life question: a possible indicator of depression among patients with lower urinary tract symptoms. AB - INTRODUCTION: Depression and benign prostatic hyperplasia (BPH) are prevalent, especially in older patient populations. Emerging data suggest potential interactions between depression and BPH. We sought to assess whether the questions of the International Prostate Symptom Score (IPSS), specifically the quality of life (QoL) question, predict depression. MATERIALS AND METHODS: We asked 541 consecutive male patients over the age of 40 in a tertiary care clinic to self-administer the IPSS QoL score and the Geriatric Depression Scale (GDS), a validated screening tool for depression. Receiver operating characteristics (ROC) curves were depicted and used to determine the area under the curve (AUC) and relative sensitivity and specificity of the individual questions of the IPSS relative to the GDS. RESULTS: Of the cohort, 17.2 percent screened positive for depression. More than half (54.7%) of nondepressed patients had a QoL score of 0 2, while a similar number of depressed patients (50.8%) had a QoL score of 5 or 6. The QoL question of the IPSS exhibited an AUC (95% CI, p value) of 0.735 (0.669-0.800, p < 0.001). A cut-off of QoL scores > 5 exhibited the highest specificity (93.1%)while a cut off of QoL scores > 1 exhibited a sensitivity of 90.0%. CONCLUSIONS: Future studies should validate these findings and shed further light on this tool's clinical utility. Pending this future validation, patients with a score of 6 could be considered for further mental health evaluation. PMID- 22316512 TI - Factors impacting survival in patients with upper tract urothelial carcinoma undergoing radical nephroureterectomy. AB - INTRODUCTION: This study aims to assess the influence of different prognostic factors on survival of upper tract urothelial carcinoma (UTUC) managed by nephroureterectomy and to investigate whether these factors have an independent prognostic significance. MATERIALS AND METHODS: A retrospective review of institutional databases from two teaching hospitals identified 269 consecutive patients with UTUC managed with nephroureterctomy between 1985 and 2005. Mean follow up was 80.6 months (median 70.3 months). Follow up was completed until January 2009. Tumor location and other clinicopathological variables were analyzed regarding survival. Data accrued included age, gender, tumor characteristics (pT stage, grade, lymph node status), tumor location, use of chemotherapy and period of diagnosis. Tumor location was divided into two groups (renal pelvis and ureter) based on the location of the tumor. RESULTS: Five year and 10 year overall survival estimates for this cohort were 71.3% and 40.0% respectively. According to tumor location, survival was 73.6% and 47.0% for the renal pelvis versus 67.8% and 32.3% for the ureter, respectively (log rank test: p = 0.027). In multivariate analysis, among the clinicopathological variables, T stage was the most significant prognostic factor (p < 0.001). Nodal involvement (p = 0,005), high grade (p < 0.001), first period of diagnosis (p < 0.001) and ureteral tumor location (p = 0.003) were significantly associated with lower survival rates. Prognosis of UTUC improved over time: survival was significantly better during the last period of diagnosis (2001-2005) (p < 0.002). CONCLUSIONS: Tumor location and diagnostic period should be considered as an independent prognostic factor for upper tract transitional cell carcinoma. PMID- 22316513 TI - Safety and outcomes of surgical treatment of renal cell carcinoma in the elderly. AB - INTRODUCTION: Treatment of the elderly patient with a small renal mass is becoming a common conundrum with scant data available to support treatment decisions. Goals were to assess risk of surgical treatment for renal cell carcinoma (RCC) in the elderly as compared to their younger counterparts. MATERIALS AND METHODS: A prospectively maintained database consisting of all renal tumors between August 2004 and November 2009 was utilized. Patients who underwent extirpative treatment for RCC were divided into groups based on age cutoff of < 75 and >= 75 years old. Primary outcome measures were likelihood of partial nephrectomy versus radical nephrectomy, complication rates, and overall and cancer-specific survival. A secondary outcome investigated was renal function. RESULTS: Of 347 patients identified, 273 were < 75, and 74 were >= 75 years old. The elderly group was less likely to undergo partial nephrectomy (26% versus 43%, p = 0.045). They also had a higher rate of pT3 disease (20% versus 11%, p = 0.018), worse baseline renal function (46 mL/min/m(2) versus 92 mL/min/m(2), p < 0.001) and a longer length of stay (3.5 days versus 2.2 days, p < 0.001). Complication rates and survival outcomes were similar between the groups. Only Eastern Cooperative Oncology Group (ECOG) >= 1 and Charlson index >= 2 predicted likelihood of experiencing a complication. CONCLUSIONS: Despite a longer length of stay, renal surgery is safe in selected elderly patients with minimal comorbidity and good functional status. The elderly have reduced baseline renal function indicating nephron sparing should be chosen whenever possible, when surgical intervention is elected. PMID- 22316514 TI - "Let's get it straight": the story of the spiral ureter. AB - A "corkscrew deformity" of the proximal ureter is a rare congenital anomaly that typically lacks any postnatal clinical significance. The rarity of this entity, however, has not allowed the clarification of its natural history and the ideal approach to its management. We herein present a case of a 27-year-old female patient who presented with right flank pain and significant hydronephrosis. On retrograde ureterography, a typical spiral configuration of the proximal ureter was noted. The patient underwent successful reconstruction by laparoscopic transperitoneal dismembered pyeloplasty. We report the first use of laparoscopic reconstruction for the management of "corkscrew deformity" of the proximal ureter and we focus on the imaging findings, technical details, advantages and limitations of this technique. PMID- 22316515 TI - Renal cell carcinoma with solitary metastasis to the bladder: mode of spread and prognosis. AB - Recurrent renal cell carcinoma (RCC) that presents as a solitary metastasis to the bladder is extremely rare. We report our experience with two patients who presented with hematuria within 1 year of their radical nephrectomy. Both patients underwent endoscopic resection of the tumor metastasis. One patient developed a metastasis in the head of pancreas 12 months following endoscopic resection. The other patient developed bilateral femoral and spinal bone metastasis. Our aim is to report our experience, and discuss the proposed modes of spread, management and prognosis. PMID- 22316516 TI - Malakoplakia of prostate as a complication of transrectal needle biopsy. AB - We report a case of a 72-year-old male that underwent two sets of transrectal prostatic needle biopsy (TPNB) within 9 month period. Pathology showed unremarkable benign prostatic tissues in the first group of biopsies while extensive diffuse inflammation with the characteristic features of malakoplakia in the second set. Three cores in the repeat biopsy contained foci of prostatic adenocarcinoma as well. Occurrence of malakoplakia several months after TPNB in our case suggests that microorganisms may have been inoculated to the prostate during the biopsy procedure. We believe that malakoplakia must be added to the list of complications after TPNB. PMID- 22316517 TI - Testicular trauma resulting in spermatic vessel thrombosis and testicular loss: a case report. AB - Testicular ischemia is typically seen with cases of testicular torsion. Twisting of the spermatic cord and compromise of testicular blood supply can induce testicular loss if not promptly discovered and treated. Non-torsion causes of testicular ischemia are uncommon with rare citations in the literature. Herein, we present a case of testicular ischemia induced by traumatic thrombosis of the spermatic vessels. PMID- 22316518 TI - Holmium laser enucleation of the prostate technique for benign prostatic hyperplasia. AB - Holmium laser resection of the prostate (HoLRP) was first described by Gilling et al in 1995. HoLRP has now evolved into holmium laser enucleation of the prostate (HoLEP) with the advent of the intravesical soft-tissue morcellator. The procedure involves anatomical dissection of the prostatic tissue off the surgical capsule in a retrograde fashion using a high-powered holmium laser followed by intravesical morcellation of the prostatic tissue. Some groups believe that the HoLEP procedure is the endoscopic equivalent to a simple open prostatectomy and may be superior to transurethral resection of the prostate (TURP) or even open prostatectomy. The objective of this article is to explain the techniques for holmium laser enucleation of the prostate (HoLEP). PMID- 22316519 TI - Open clinical uro-oncology trials in Canada. PMID- 22316520 TI - Optimal port placement during laparoscopic radical prostatectomy. AB - INTRODUCTION: Placement of anterior abdominal wall trocars during laparoscopic radical prostatectomy (LRP) carries the risk of inadvertent injury to the inferior epigastric artery (IEA) and crossover confliction between midline and lateral ports. We described and evaluated a new measured port placement approach. MATERIALS AND METHODS: The intervention group included patients who underwent LRP with a specifically measured five port approach. The medial 10 mm ports were placed 5 cm from the patient's midline at a level mid-way between the anterior superior iliac spine (ASIS) and the umbilicus. The control group had five ports placed at the surgeon's discretion. We prospectively compared intraoperative blood loss, need for port repositioning, and incidence of adverse surgical events. RESULTS: In the interventional cohort patients (n = 112) the course of the IEA was found to be lateral to the medial 10 mm port in all cases. There were no adverse surgical outcomes in this group. In the control group patients (n = 97), three demonstrated IEA injuries (p <0.01) and three required port repositioning (p < 0.01). The mean blood loss reported between groups was not significant (p = 0.70). CONCLUSION: Our specifically measured port placement approach predictably allowed for the placement of the trocar medial to the IEA. This minimized the risk of injury to the IEA, allowed for adequate instrument manipulation and minimized the need to reposition ports. PMID- 22316521 TI - Controlling the dorsal venous complex during robotic prostatectomy. AB - INTRODUCTION: The objective of our study was to determine whether dorsal venous complex (DVC) control technique influences positive apical margins following robotic assisted laparoscopic radical prostatectomy (RALRP). MATERIALS AND METHODS: One thousand fifty-eight patients who underwent RALRP at City of Hope from June 2007 to October 2009 were assessed. Endoscopic stapling and suture ligature of the DVC were compared. Positive apical margins were identified and compared based on DVC-control technique. Recurrence probability was estimated using the Kaplan-Meier method, and logistic regression analysis was used to predict the odds of positive apical margins. RESULTS: Of 1058 patients, 633 (60%) underwent endoscopic stapling, and 425 (40%) had suture ligature. The groups had similar baseline characteristics including age and body mass index. We observed a statistically different PSA (5.4 ng/mL versus 5.2 ng/mL, p = 0.03) and operative time (2.8 hours versus 2.7 hours, p = 0.02) between stapling and suture groups, but the actual difference was small. Operative time, Gleason score, pathologic stage, and overall positive margin rates were not significantly different between groups. Positive apical margins were observed in 39 (6%) and 27 (6%) patients in the staple and suture groups, respectively. Multivariate analysis showed that the positive apical margin rate was greater in patients with higher pathologic stage and final pathological Gleason score. CONCLUSIONS: During RALRP, there is no difference in positive apical margin rate when the DVC is controlled using either endoscopic stapling or suture ligature. However, patients with a higher pathologic stage and final pathologic Gleason score are at higher risk for positive apical surgical margins. PMID- 22316522 TI - Attempted reversible sympathetic ganglion block by an implantable neurostimulator. AB - OBJECTIVE: Primary palmar hyperhidrosis is a pathological condition of excessive perspiration of the hands of unknown aetiology. The only effective treatment for permanent cure is the ablation of the sympathetic ganglia supplying the hands. One of the sequelae is compensatory sweating, namely increased perspiration in other parts of the body. Its mechanism is unknown. In a small proportion of patients, it may attend devastating proportions. It has practically no remedy, and the degree of compensatory hyperhidrosis is unpredictable prior to sympathectomy. The purpose of the present study was to obtain a reversible sympathetic block which may disclose subjects prone to develop severe compensatory hyperhidrosis and unfit for permanent ganglionic ablation. METHODS: In three dogs, an experimental electrode was implanted via a left thoracotomy on the stellate ganglion, connected to a stimulator. The stimulation was activated after recovery. The contralateral ganglion served as control. Effect of the stimulation was assessed by observing the development of Horner's syndrome, which includes the appearance of miosis, ptosis and enophthalmus. Reversal of the sympathetic block was expected when the neurostimulation was discontinued and assessed by the disappearance of these signs. RESULTS: Stimulation produced only a partial effect - an incomplete Horner's syndrome (miosis and sometime ptosis), which was not completely reversible after ceasing the stimulation. CONCLUSIONS: Although neurostimulation achieved a partial sympathetic block, the present method failed to obtain a completely reversible effect. However, these results may indicate that different nervous pathways moderate the various components of the Horner's triad. Concerning the creation of a reversible sympathectomy; other approaches must be sought after. PMID- 22316523 TI - Quantitative statistical analysis of standard and human blood proteins from liquid chromatography, electrospray ionization, and tandem mass spectrometry. AB - It will be important to determine if the parent and fragment ion intensity results of liquid chromatography, electrospray ionization and tandem mass spectrometry (LC-ESI-MS/MS) experiments have been randomly and independently sampled from a normal population for the purpose of statistical analysis by general linear models and ANOVA. The tryptic parent peptide and fragment ion m/z and intensity data in the mascot generic files from LC-ESI-MS/MS of purified standard proteins, and human blood protein fractionated by partition chromatography, were parsed into a Structured Query Language (SQL) database and were matched with protein and peptide sequences provided by the X!TANDEM algorithm. The many parent and/or fragment ion intensity values were log transformed, tested for normality, and analyzed using the generic Statistical Analysis System (SAS). Transformation of both parent and fragment intensity values by logarithmic functions yielded intensity distributions that closely approximate the log-normal distribution. ANOVA models of the transformed parent and fragment intensity values showed significant effects of treatments, proteins, and peptides, as well as parent versus fragment ion types, with a low probability of false positive results. Transformed parent and fragment intensity values were compared over all sample treatments, proteins or peptides by the Tukey-Kramer Honestly Significant Difference (HSD) test. The approach provided a complete and quantitative statistical analysis of LC-ESI-MS/MS data from human blood. PMID- 22316526 TI - Aging is associated with circulating cytokine dysregulation. AB - PURPOSE: Aging is accompanied by a progressive increase in pro-inflammatory cytokine status. However, little is known about the development of age-dependent modifications in other circulating cytokines. The aim of this study was to investigate in vivo the influence of age on circulating cytokine production in healthy subjects (HC). METHODS: Circulating cytokines were measured by CBA and ELISA in 73 HC. Intracellular cytokine production was assessed in CD3+ and CD14+ cells by flow cytometry. Production of cytokines in cell culture supernatants was also studied after polyclonal stimulation. RESULTS: Subjects were divided into three different groups according to age: 28 young HC (<30 years, 26.2 +/- 2.4), 24 middle age HC (30-60 years, 44.7 +/- 8.4) and 21 elderly HC (>60 years, 70.6 +/- 7.9). Age was positively correlated with the circulating levels of IL-12p70, IL-1beta, TNFalpha, IL-6, and IL-10. Age had a negative correlation with circulating levels of IL-17. Besides, age was positively correlated with spontaneous intracellular expression of proinflammatory cytokines in circulating monocytes. No correlation was found with other intracellular cytokine expression or with the production of cytokines in cell culture supernatants after in vitro stimulation. Gender had a marginal effect on the circulating cytokine profile. CONCLUSION: Aging has a significant impact on the production of circulating cytokines in healthy individuals. The circulating cytokine milieu may contribute to the development of age-restricted conditions. PMID- 22316527 TI - [Evaluation of a mechanical ventilation associated pneumonia prevention program: results after one year]. AB - INTRODUCTION: With the aim of improving healthcare quality and safety of the patient, a multidisciplinary program was introduced and directed at the prevention of Mechanical Ventilation Associated Pneumonia (MVAP), following a continuous improvement cycle of PDCA (Plan, Do, Check, Adjust). An analysis of the measures applied is presented. AIMS: Evaluation of the MVAP prevention program: theoretical knowledge, and fulfilment of the measures proposed. Analysis of the annual MVAP variation. MATERIAL AND METHODS: Acquired knowledge was evaluated through questionnaires. The results of the fulfilment of the measures proposed (elevation of the bed headboard, optimal pressure of the cuff, and oral hygiene) were analysed through monthly audits. Calculation of annual rate of MVAP and respiratory infections. RESULTS: The knowledge of MVAP and its prevention had improved (P<.05). Preventive measures: Significant difference in the maintenance of headboard at >30 degrees (P<.05) and in the performing of oral hygiene (P<.05). Improvement in the maintenance of cuff pressure between 20 and 30cm H2O (P=.13). Decline and stabilization of yearly rate of MVAP (0.7%). CONCLUSIONS: The introduction of a training program and of a set of preventive non pharmacological measures decreased the incidence of MVAP. PMID- 22316528 TI - Spatial and temporal thermal analysis of acousto-optic deflectors using finite element analysis model. AB - Thermal effects greatly influence the optical properties of the acousto-optic deflectors (AODs). Thermal analysis plays an important role in modern AOD design. However, the lack of an effective method of analysis limits the prediction in the thermal performance. In this paper, we propose a finite element analysis model to analyze the thermal effects of a TeO(2)-based AOD. Both transducer heating and acoustic absorption are considered as thermal sources. The anisotropy of sound propagation is taken into account for determining the acoustic absorption. Based on this model, a transient thermal analysis is employed using ANSYS software. The spatial temperature distributions in the crystal and the temperature changes over time are acquired. The simulation results are validated by experimental results. The effect of heat source and heat convection on temperature distribution is discussed. This numerical model and analytical method of thermal analysis would be helpful in the thermal design and practical applications of AODs. PMID- 22316529 TI - A virtual pyrogram generator to resolve complex pyrosequencing results. AB - We report a freely available software program, Pyromaker, which generates simulated traces for pyrosequencing results based on user inputs. Simulated pyrograms can aid in the analysis of complex pyrosequencing results in which various hypothesized mutations can be tested, and the resultant pyrograms can be matched with the actual pyrogram. We validated the software using the actual pyrograms for common KRAS gene mutations as well as several mutations in the BRAF, GNAS, and p53 genes. We demonstrate that all 18 possible single-base mutations within codons 12 and 13 of KRAS generate unique pyrosequencing traces and highlight the distinctions between them. We further show that all reported codon 12 and 13 complex mutations produce unique pyrograms. However, some complex mutations are indistinguishable from single-base mutations. For complicated pyrograms, Pyromaker was used in two modes, one in which hypothesis-based simulated pyrograms were pattern-matched with the actual pyrograms. In a second strategy with only the pyrogram, Pyromaker was used to identify the underlying mutation by iteratively reconstructing the mutant pyrogram. Either strategy was able to successfully identify the complex mutations, which were confirmed by cloning and sequencing. Using two examples of KRAS codon 12 mutations (specifically GGT->TTT, G12F and GGT->GAG, G12E), we report which combinations of five approaches permit unambiguous mutation identification. The most efficient approach was found to be pyrosequencing with Pyromaker. PMID- 22316531 TI - Carbon nanotube bundles under electric field perturbations. AB - Here we address the important role played by electric fields applied in carbon nanotube bundles in providing convenient scenarios for their use in electronic devices. We show that a gap modulation may be derived depending on the bundle configuration and the details of the applied field configuration. The system is described by a tight binding Hamiltonian and the Green function formalism is used to calculate the local density of states. Small bundles were used to validate our model on the basis of ab initio calculations. Further analysis shows that the number of tubes, geometrical configuration details and field intensities may be controlled to tune the electronic structure close to the Fermi energy, envisaging atomic-scale devices. PMID- 22316532 TI - Adequacy of depression treatment among college students in the United States. AB - OBJECTIVE: There is no published evidence on the adequacy of depression care among college students and how this varies by subpopulations and provider types. We estimated the prevalence of minimally adequate treatment among students with significant past-year depressive symptoms. METHOD: Data were collected via a confidential online survey of a random sample of 8488 students from 15 colleges and universities in the 2009 Healthy Minds Study. Depressive symptoms were assessed by the Patient Health Questionnaire-2, adapted to a past-year time frame. Students with probable depression were coded as having received minimally adequate depression care based on the criteria from Wang and colleagues (2005). RESULTS: Minimally adequate treatment was received by only 22% of depressed students. The likelihood of minimally adequate treatment was similarly low for both psychiatric medication and psychotherapy. Minimally adequate care was lower for students prescribed medication by a primary care provider as compared to a psychiatrist (P<.01). Racial/ethnic minority students were less likely to receive depression care (P<.01). CONCLUSIONS: Adequacy of depression care is a significant problem in the college population. Solutions will likely require greater availability of psychiatry care, better coordination between specialty and primary care using collaborative care models, and increased efforts to retain students in psychotherapy. PMID- 22316530 TI - Targeting polymer therapeutics to bone. AB - An aging population in the developing world has led to an increase in musculoskeletal diseases such as osteoporosis and bone metastases. Left untreated many bone diseases cause debilitating pain and in the case of cancer, death. Many potential drugs are effective in treating diseases but result in side effects preventing their efficacy in the clinic. Bone, however, provides a unique environment of inorganic solids, which can be exploited in order to effectively target drugs to diseased tissue. By integration of bone targeting moieties to drug-carrying water-soluble polymers, the payload to diseased area can be increased while side effects decreased. The realization of clinically relevant bone targeted polymer therapeutics depends on (1) understanding bone targeting moiety interactions, (2) development of controlled drug delivery systems, as well as (3) understanding drug interactions. The latter makes it possible to develop bone targeted synergistic drug delivery systems. PMID- 22316533 TI - [Clinical observation of therapeutic effect of extracorporeal membrane oxygenation in patients with acute respiratory distress syndrome]. AB - OBJECTIVE: To investigate the therapeutic effects and safety of extracorporeal membrane oxygenation (ECMO) in patients with acute respiratory distress syndrome (ARDS). METHODS: ECMO were initiated in 6 patients with ARDS, not responding to conventional mechanical ventilation. Oxygenation status, positive end-expiratory pressure (PEEP) level, and fraction of inspired oxygen [FiO(2)] were compared before and after treatment with ECMO, while the adverse effects of ECMO were recorded. RESULTS: In 6 cases, pulse blood oxygen saturation [SpO(2)] was elevated (0.45-0.92 up to 0.94-1.00), PEEP level [cm H(2)O, 1 cm H(2)O=0.098 kPa] and [FiO(2)] were lowered [PEEP: 10.0-22.0 down to 4.0-15.0; FiO(2): 1.00 down to 0.30-0.60] after treatment with ECMO. Of 6 cases, 2 patients with severe influenza A/H1N1 pneumonia finally died of shock; 1 patient with severe influenza A/H1N1 pneumonia and 1 patient with Klebsiella pneumoniae pneumonia were withdrawn from ECMO treatment because of deterioration of the disease. One patient suffering from Cytomegalovirus pneumonia and another with Acinetobacter baumannii pneumonia were successfully discharged from hospital with recovery. The main complications were bleeding and hemolysis. CONCLUSIONS: ECMO could improve gas exchange, oxygenation and partially replace pulmonary function. Patients with ARDS should be treated with ECMO early if artificial ventilation treatment was unresponsive. PMID- 22316534 TI - [Concerning about current researching status of difficult-to-wean from mechanical ventilation]. PMID- 22316535 TI - [Does the humidified high-flow nasal oxygen therapy decrease need for intubation in the acute respiratory failure adult patient?]. PMID- 22316536 TI - [Clinical observational study of anemia in mechanically ventilated patients]. AB - OBJECTIVE: To explore the prognostic effects of anemia among the mechanically ventilated patients. METHODS: A prospective observational study was undertaken in a 12-bed intensive care unit (ICU). Patients requiring mechanical ventilation for at least 72 hours and hemoglobin (Hb)>=100 g/L were enrolled. Serum erythropoietin (EPO), Fe(3+), transferrin (TRF) levels were measured as baseline when they were enrolled and were repeated at day 3, 7 and 14. According to Hb concentration at day 3, patients were divided into anemia group (defined as Hb<100 g/L) and non-anemia group. Serum EPO, Fe(3+), TRF at day 1, 3 and 7, and mean amount of blood transfusion within 14 days, mean volume of blood drawn daily in 3, 7 and 14 days, the survival rate with unassisted breathing at day 28, ICU mortality, length of ICU stay, ventilator days, length of hospital stay and 28 day mortality were compared. RESULTS: Forty mechanically ventilated patients were enrolled and divided into anemia group (n = 18) and non-anemia group (n = 22). It was shown that the anemia group had lower serum Fe(3+) concentration, and higher serum EPO and TRF. The anemia group also had more transfusion [U: 4.0 (2.0, 6.0) vs. 2.0 (0.0, 2.0), P < 0.01], longer length of hospital stay [days: 35.0 (16.5, 51.6) vs. 24.5 (10.0, 35.8), P < 0.05], decreased rate of survival with unassisted breathing at day 28 (44.4% vs. 72.7%, P < 0.05) and higher ICU mortality (44.4% vs. 13.6%, P < 0.05). But there were no significant differences between anemia group and control group in mechanical ventilated days (days: 18.3 +/- 10.8 vs. 11.6 +/- 8.2, P > 0.05), length of ICU stay [days: 16.5 (8.0, 21.5) vs. 11.0 (5.8, 18.3),P > 0.05] and hospital mortality (61.1% vs. 31.8%, P > 0.05). CONCLUSION: The anemic patients had longer ventilator days, hospital stay, higher ICU mortality, and lower rate of survival with unassisted breathing at day 28. PMID- 22316537 TI - [A comparative study between inflation and deflation pressure-volume curve in determining the optimal positive end-expiratory pressure]. AB - OBJECTIVE: To determine the optimal positive end-expiratory pressure (PEEP) according to inflation and deflation pressure-volume curve (P-V curve) in patients with acute respiratory distress syndrome (ARDS). METHODS: ARDS models were reproduced in 20 dogs, and they were randomly divided into two groups. In both groups, Levenberg-Marquardt iterative algorithm was employed using software to explore parameters fitting with Boltzmann formula, by which the real inflection point of pressure (Pinf d) in deflation limb or lower inflection point pressure (PLip) in inflation limb on P-V curve were defined. For the control group (inflation curve) P-V curve of PLip + 2 cm H(2)O [1 cm H(2)O = 0.098 kPa] was applied as the best PEEP value. In the experimental group (deflation curve) the Pinf d was taken as the best PEEP value. The heart rate (HR), blood pressure (BP), fingertip pulse oxygen saturation [SpO(2)], static lung compliance (Cst), arterial partial pressure of oxygen [PaO(2)] and arterial partial pressure of carbon dioxide [PaCO(2)] were monitored at 0, 2, 6, 12, 24 and 48 hours. RESULTS: Oxygenation index increased significantly both in control and experimental groups. In experimental group, oxygenation index (mm Hg, 1 mm Hg = 0.133 kPa) of 12, 24 and 48 hours was respectively significantly higher than that of the control group (12 hours: 177.63 +/- 8.94 vs. 165.60 +/- 8.90, 24 hours: 194.19 +/ 10.67 vs. 168.70 +/- 10.60, 48 hours: 203.15 +/- 13.21 vs. 171.26 +/- 9.21, all P < 0.01). Cst [ml/cm H(2)O] at 2, 6, 12, 24 and 48 hours was respectively higher than that of the control group (2 hours: 41.00 +/- 4.17 vs. 36.20 +/- 3.90, 6 hours: 44.00 +/- 4.65 vs. 36.88 +/- 3.39, 12 hours: 46.92 +/- 5.47 vs. 37.92 +/- 3.10, 24 hours: 42.83 +/- 8.97 vs. 37.92 +/- 3.09, 48 hours: 42.64 +/- 9.04 vs. 37.97 +/- 2.98, P < 0.05 or P < 0.01). CONCLUSION: Determining optimal PEEP for ARDS with deflation P-V curve was better than that of inflation curve. PMID- 22316538 TI - [Use of extracorporeal membrane oxygenation in adults with acute respiratory distress syndrome: a meta-analysis]. AB - OBJECTIVE: To evaluate the effects of extracorporeal membrane oxygenation (ECMO) on mortality in adult patients with acute respiratory distress syndrome (ARDS). METHODS: Literature concerning randomized controlled trials (RCTs), case-control studies and prospective cohort studies from January 1966 to July 2011 on ECMO for the treatment of ARDS patients was retrieved by electronic and manual search. Meta-analysis of the use of ECMO in the treatment of ARDS patients was conducted using the methods recommended by the Cochrane Collaboration's software RevMan 5.0. RESULTS: Three papers reporting RCTs and 6 papers concerning observational cohort studies of using ECMO in patients with severe ARDS were enrolled for analysis. Meta-analysis of the 3 RCTs (310 patients, 159 of them treated with ECMO) revealed ECMO did not decrease the mortality of ARDS patients [odds ratio (OR)=0.75, 95% confidence interval (95%CI) 0.45-1.24, P = 0.27]. Meta-analysis of the all 9 studies (1058 patients, 386 of them treated with ECMO) revealed ECMO increased the mortality of ARDS patients (OR=1.58, 95%CI 0.94-2.67, P = 0.08). CONCLUSION: There is no evidence to prove that ECMO is beneficial in adult patients with ARDS, therefore further investigation with a large sample of high quality RCT is warranted. PMID- 22316539 TI - [The application of extracorporeal membrane oxygenation in critically ill patient]. AB - OBJECTIVE: To evaluate the supportive effects on cardiopulmonary failure in critically ill patients treated with extracorporeal membrane oxygenation (ECMO). METHODS: A retrospective observational study of 9 patients treated in intensive care unit (ICU) of Peking University Third Hospital and Beijing Ditan Hospital from October 1, 2007 to December 26, 2009 with ECMO for various diseases was conducted. Clinical data was analyzed. RESULTS: Of 9 patients [mean age (26.8 +/- 7.0) years, body mass index (28.3 +/- 9.1) kg/m(2)] were enrolled, 3 were male and 6 were female. Two patients were treated with veno-arterial(V-A) ECMO for severe heart failure, and 7 with veno-venous(V-V) ECMO due to refractory acute respiratory distress syndrome ARDS caused by 2009 novel H1N1 virus infection. The doses of vasoactive agents and cardiac parameters changed greatly after the V-A mode. The setting of ventilator support were significantly decreased, and arterial oxygen saturation [SaO(2)], arterial blood carbon dioxide partial pressure [PaCO(2)] and blood pH value were improved significantly after the V-V mode ECMO. Acute renal insufficiency occurred in 5 patients, hyperbilirubinemia in 6 patients, and catheter related blood stream infection in 4 patients. Five patients were weaned from ECMO successfully and 4 of them rehabilitated, the treatment was withdrawn in 2 patients, and the other 2 patients died during the procedure. The mean amount of red blood cell suspension administered per patients was (15.1 +/- 9.9) U, and length of ICU stay was (18.9 +/- 15.7) days. CONCLUSIONS: ECMO has a rapid effect to temporarily support heart or lung function (partially or totally) during cardiopulmonary failure, leading to organ recovery. Attempts to reduce the incidence of complications might improve the prognosis of critically ill patients. PMID- 22316540 TI - [The value of assay of (1, 3)-beta-D-glucan in bronchoalveolar lavage fluid for detection of invasive pulmonary fungal infection in critically ill patients in intensive care unit]. AB - OBJECTIVE: To evaluate the value of (1, 3)-beta-D-glucan (G test) in bronchoalveolar lavage fluid (BALF) in diagnosing and determining the therapeutic effects among the critically ill patients suspected with invasive pulmonary fungal infection (IPFI). METHODS: Study was conducted between February 2010 and August 2011 in medical intensive care unit (MICU) of the Affiliated Hospital of Guiyang Medical College. Patients suspected of suffering from IPFI were enrolled. G tests of BALF and serum, and culture and microscopic examination of BALF were performed twice weekly.Clinical feature, mycological evidence and the results of G test were recorded. The results of IPFI were defined as "proven", "probable", "possible" and "non-IPFI". G test in BALF and serum was done with tachypleus amebocyte lysate. Positive G test was defined as cut-off index >=20 ng/L in two consecutive measurements. Furthermore, the patients with positive G test received preemptive antifungal therapy with fluconazole or itraconazole. G tests of BALF and serum were respectively done on 7th day and 14th day of treatment. RESULTS: Ninety-eight patients were included. Among them, 10 patients were "proven" in whom the positive rate of BALF G test was 90.0%; 29 patients the results were considered as "probable" in whom the positive rate of BALF G test was 82.8%; in 32 patients the results were "possible" IPFI in whom the positive rate of BALF G test was 71.9%, 27 patients were "non-IPFI" in whom the positive rate of BALF G test was 7.4%. The positive rate of BALF G test was 84.6% (33/39), the positive rate of serum G test was 59.0% (23/39), the positive rate of culture of BALF was 41.0% (16/39), the positive rate of microscopic examination of BALF was 38.5% (15/39) in "proven" cases and "probable" cases. G test (cut-off >=20 ng/L) of BALF had shown to have sensitivity, specificity, positive predictive value (PPV) of 84.6% (33/39), 92.6% (25/27), 94.3% (33/35), respectively, and negative predictive value (NPV) of 80.7% (25/31). The G test detection (cut-off >=20 ng/L) in serum had shown to have sensitivity, specificity, PPV of 58.9% (23/39), 88.9% (24/27), 88.5%(23/26), respectively, and NPV of 60.0% (24/40), and the differences in sensitivity were statistically significant (P < 0.05). BALF G test assay tended to become positive earlier than the culture for 2-8 days with mean of (5.35 +/- 2.26) days.Forty out of 56 G test positive patients were given preemptive antifungal therapy for 2 weeks, and there was a good response in 31 patients, but no response in 9 cases with 22.5% mortality. After treatment, the result of G test (ng/L) was lowered in patients with a good response in treatment group (BALF: 245.13 +/- 43.84, 174.00 +/- 13.01, 28.52 +/- 7.38; serum: 93.26 +/- 18.75, 72.15 +/- 12.90, 37.37 +/- 10.45, all P < 0.05). On the other hand, an elevated value suggested an unsatisfactory result in ineffective group (BALF: 267.58 +/- 54.63, 309.71 +/- 82.47, 486.72 +/- 98.21; serum: 101.58 +/- 12.75, 98.07 +/- 27.45, 112.07 +/- 19.21, all P < 0.05). There were significantly differences in the results of G tests on 7th day and 14th day between BALF G test and serum G test in both groups (all P < 0.05). CONCLUSIONS: It is suggested that BALF G test may be an useful test for early diagnosis of IPFI. Moreover, the dynamic change in G test values could be useful for assessing therapeutic response. PMID- 22316541 TI - [Significance of identification of fungi in gastric juice of patients with artificial airway in intensive care unit]. AB - OBJECTIVE: To investigate the direct relationship and significance between the pH value of gastric juice and positive fungi in culture critical patients with artificial airway in intensive care unit (ICU) by analyzing and identifying the type of fungi and their sensitivity to antifungal therapy. METHODS: A prospective study was conducted.One hundred and sixty patients (between December, 2008 and October, 2011) with artificial airway lasting longer than 48 hours were studied in the ICU at the First Affiliated Hospital of Shenzhen University. The gastric juice specimens were collected through a nasogastric tube, their pH values were measured using precise litmus paper. These samples were divided into six groups according to their pH values: pH <= 2.0, pH 2.1-3.0, pH 3.1-4.0, pH 4.1-5.0, pH 5.1-6.0 and pH 6.1-7.0, and then fungi were cultured in these specimens with different pH values. Susceptibility of different fungicide drugs were also investigated. The susceptibility of fungi to gastric juice with different pH values was also investigated. The relationship between 28-day survival rate and the presence of fungi in gastric juice was analyzed in order to analyze the relationship of the presence of fungi in gastric juice and clinical outcome. RESULTS: (1) No fungal growth was found in the gastric juice with pH value lower than 4.0, and the positive rate of fungal culture was significantly increased when the pH value of gastric juice raised. (2) The positive rate of fungal growth was 27.9% (55/197), in which, the positive rate of Candida and non-Candida fungi was 38.2% (21/55) and 61.8% (34/55) respectively, and the difference was significant statistically [chi(2) = 4.16, P < 0.05]. (3) The fungal positive rate was 40.0% (22/55) and 60.0% (33/55) respectively, in survivors (102 cases) and non-survivors (58 cases). The percentage of Candida infection and non-Candida infection was 54.5% (12/22) and 45.5% (10/22) respectively, in survivors, and it was 27.3% (9/33) and 72.7% (24/33), respectively, in non-survivors. The rate of resistance of Candida and non-Candida fungi was 4.7%-14.3% (mean 10.1%) and 0-60% (mean 28.5%) respectively. CONCLUSIONS: Positive fungus culture rate was higher in critical patients with artificial airway and higher gastric juice pH values. Non-Candida fungi were mainly found in gastric juice with increasing resistance rate. Candida was more commonly found in survivors, and non-Candida fungi were more commonly found in non-survivors. PMID- 22316542 TI - [The changes in subgroup of helper T lymphocyte and calcitonin and their correlation in patients with severe hospital acquired pneumonia]. AB - OBJECTIVE: To observe the changes in subgroups of helper T cells and serum calcitonin (PCT) levels in patients with hospital acquired pneumonia (HAP) and their correlation. METHODS: Eighty-nine patients with diagnosis of HAP (severe in 59 patients, mild in 30 cases) were included, with 20 healthy adults as control. Percentage of CD4(+), Th1 and Th2 cells, and Th1/Th2 ratio were determined, and sandwich immune luminescence was used to detect the level of serum PCT. RESULTS: The percentage of Th1 cells [(8.40 +/- 3.01)%] was significantly lower in patients with severe HAP compared with that of mild pneumonia group [(13.90 +/- 2.37)%, P < 0.05] and healthy controls [(17.40 +/- 4.20)%, P < 0.01]. Percentage of Th2 cells was obviously higher in patients with severe HAP [(17.30 +/- 5.74)%] than mild pneumonia group [(7.70 +/- 2.35)%, P < 0.05] and healthy controls [(7.90 +/- 1.92)%, P < 0.01]. Th1/Th2 ratio was also obviously lower in severe pneumonia group (0.57 +/- 0.15) than that of mild pneumonia group (2.80 +/- 0.46, P < 0.01) and healthy controls (3.11 +/- 0.87, P < 0.01). Compared with healthy controls, Th1 cells in mild pneumonia patients were reduced significantly (P < 0.05), but there was no significant difference in Th2 cells and Th1/Th2 ratio (both P > 0.05). There was no difference in CD4(+) among severe, mild pneumonia and healthy controls [(30.20 +/- 10.83)%, (34.70 +/- 13.57)%, (28.80 +/- 9.61)%, respectively, all P >0.05]. The level of PCT (MUg/L) was significantly elevated in mild and severe pneumonia patients compared with that of healthy controls (1.73 +/- 0.88, 3.51 +/- 2.66 vs. 0.30 +/- 0.10, both P < 0.01), and the level of PCT in severe pneumonia was significantly higher than that of mild pneumonia (P < 0.05). Regression analysis of Th1/Th2 and PCT revealed a significant negative correlation, with regression equation Y = -0.937x (F=236.23,P = 0.0000). CONCLUSIONS: Patients with severe HAP had obvious imbalance of Th1/Th2. The suppression of cellular immune function, reduction in Th2 cells and exacerbation of anti-inflammatory reaction intensify the infection leading to multiple organ dysfunction syndrome. There is obvious negative correlation between Th1/Th2 and PCT. PCT could be used as an indicator of immune response in reflecting cellular and humoral immunity of the patient. PMID- 22316543 TI - [Effects of recruitment maneuver in prone position on hemodynamics in patients with severe pulmonary infection]. AB - OBJECTIVE: To evaluate effects of recruitment maneuver in prone position on hemodynamics in patients with severe pulmonary infection, based on the protective pulmonary ventilation strategy. METHODS: Ninety-seven cases with severe pulmonary infection admitted to intensive care unit (ICU) of Ganzhou City People's Hospital undergoing mechanical ventilation were involved. Volume controlled ventilation mode with small tidal volume (8 ml/kg) and positive end-expiratory pressure (PEEP) of 6 cm H(2)O [1 cm H(2)O = 0.098 kPa] was conducted. Each patient underwent recruitment maneuver in supine position and then in prone position [PEEP 20 cm H(2)O+pressure control (PC) 20 cm H(2)O]. Heart rate (HR), mean arterial pressure (MAP), pulse oxygen saturation [SpO(2)] and blood gas analysis data were recorded before and after recruitment maneuver in either position. A double-lumen venous catheter was inserted into internal jugular vein or subclavian vein, and a pulse index contour cardiac output (PiCCO) catheter was introduced into femoral artery. Cardiac index (CI), stroke volume index (SVI), systemic vascular resistance index (SVRI), intra-thoracic blood volume index (ITBVI), extra vascular lung water index (EVLWI), global end-diastolic volume index (GEDVI), global ejection fraction (GEF), stroke volume variation (SVV) and central vein pressure (CVP) were monitored. RESULTS: (1) Compared with data before recruitment maneuver, there were no significant differences in HR and MAP after supine position and prone position recruitment maneuver, but significant differences in SpO(2) were found between before and after recruitment maneuver when patients' position was changed (supine position: 0.954 +/- 0.032 vs. 0.917 +/- 0.025, P < 0.05; prone position: 0.982 +/- 0.028 vs. 0.936 +/- 0.039, P < 0.05). SpO(2) was higher in prone position recruitment maneuver (P < 0.05). (2) Compared with data before recruitment maneuver, CI [L*min(-1)*m(-2)], SVI (ml/m(2)), GEDVI (ml/m(2)) and GEF were decreased significantly during recruitment maneuver (supine position: CI 3.2 +/- 0.4 vs. 3.8 +/- 0.6, SVI 32.4 +/- 5.6 vs. 38.8 +/- 6.5, GEDVI 689 +/- 44 vs. 766 +/- 32, GEF 0.267 +/- 0.039 vs. 0.305 +/- 0.056; prone position: CI 3.1 +/- 0.5 vs. 3.6 +/- 0.4, SVI 31.2 +/- 5.8 vs. 37.3 +/- 5.0, GEDVI 678 +/- 41 vs. 758 +/- 36, GEF 0.268 +/- 0.040 vs. 0.288 +/- 0.053, all P < 0.05), and CVP [cm H(2)O] and SVV were significantly increased [supine position: CVP 10.7 +/- 1.5 vs. 8.2 +/- 2.5, SVV (11.2 +/- 3.3)% vs. (8.3 +/- 4.7)%; prone position: CVP 10.3 +/- 1.8 vs. 8.1 +/- 2.5, SVV (12.7 +/- 3.4)% vs. (9.1 +/- 3.6)%, all P < 0.05], but they returned to the level of that before recruitment maneuver soon after termination of recruitment maneuver. There were no significant differences in SVRI, ITBVI and EVLWI between before and after recruitment maneuver in both positions. There were also no significant differences in above parameters between two positions. CONCLUSIONS: Based on the lung protective ventilation strategy of small tidal volume with PEEP, oxygenation was improved and SpO(2) was increased significantly when prone position ventilation combined with lung recruitment method was used in severe pulmonary infection patients. The effect of recruitment maneuver during prone position on hemodynamics was slight, except a temporary decrease of SVI and GEF just during recruitment maneuver. PMID- 22316544 TI - [Effects of volume resuscitation on venous pressure gradient in hypovolemic patients undergoing mechanical ventilation]. AB - OBJECTIVE: To investigate the value of venous pressure gradient [D(c-i)VP] between central venous pressure (CVP) and iliac vein pressure (IVP) in assessing the responsiveness to volume resuscitation in hypovolemic patient undergoing mechanical ventilation. METHODS: Thirty hypovolemic patients undergoing mechanical ventilation, with maintenance of similar ventilation conditions, graded volume loading was performed with 250 ml Ringer lactate solution (LR) for each infusion in hypovolemic patients, until mean arterial pressure (MAP) >=65 mm Hg(1 mm Hg = 0.133 kPa), CVP>=8 mm Hg, strong pulse, perfusion improvement (recovery in the end) were reached. Before infusion, 10 minutes after infusion, and at the end of recovery, the heart rate (HR), MAP, CVP, IVP, stroke volume (SV), thoracic fluid content (TFC) and D(c-i)VP were measured and recorded, the correlations between D(c-i)VP and TFC, SV before and after infusion were analyzed. RESULTS: Before infusion, 10 minutes after infusion, and at the end of recovery, no significant difference was found in HR, MAP, CVP, and IVP,while D(c-i)VP (mm Hg) was obviously lowered (4.89 +/- 1.70, 2.80 +/- 1.44, 2.10 +/- 1.30, respectively), and SV (ml) and TFC (ml) were significantly increased (SV was 42.0 +/- 10.5, 49.0 +/- 8.3, 58.0 +/- 12.1, respectively; TFC was 30.0 +/- 9.6, 38.0 +/- 8.6, 43.0 +/- 11.1, respectively), with statistical differences (P < 0.05 or P < 0.01). Negative correlations were found between D(c i)VP and TFC, SV [r(1)=-0.580, P(1)=0.004; r(2)=-0.462, P(2) =0.017]. CONCLUSIONS: In the course of fluid resuscitation in hypovolemic patients undergoing mechanical ventilation, the D(c-i)VP was significantly reduced with fluid resuscitation. At the same time, significant correlations between D(c i)VP, TFC and SV were demonstrated. The measurement of D(c-i)VP could help guide fluid resuscitation in hypovolemic patients undergoing mechanical ventilation. PMID- 22316545 TI - [Protective effect of N-acetylcysteine against pneumocyte apoptosis during ischemia/reperfusion injury of lung in rats]. AB - OBJECTIVE: To investigate the effect of N-acetylcysteine (NAC) on apoptosis of pneumocytes and expression of caspase-3 during lung ischemia/reperfusion injury (LIRI) in rats, and to explore the possible role of NAC in pneumocyte apoptosis. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into three groups: sham operation group, LIRI group (LIRI was produced by 45 minutes of clamping of the pulmonary hilum followed by 3 hours or 6 hours of reperfusion), and NAC group (NAC 150 mg/kg was injected intraperitoneally before LIRI). Lung specimens were harvested 3 hours or 6 hours after LIRI. Apoptosis rate in lung tissue was determined with flow cytometer after Annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI) staining. Malondialdehyde (MDA, thiobarbituric acid) and superoxide dismutase (SOD, xanthine oxidase) of lung tissue were measured. Expression of caspase-3 in lung was determined by reverse transcription-polymerase chain reaction (RT-PCR), and the changes in ultrastructure of lung tissue were observed by electron microscope. RESULTS: Compared with that of the sham operation group, apoptosis rate of pulmonary cells was significantly increased at 3 hours and 6 hours in LIRI group [(25.60 +/- 3.22)% vs. (2.19 +/- 0.48)% , (26.01 +/- 4.50)% vs. (2.55 +/- 0.36)%], the content of MDA (nmol/mg) was significantly increased (3.26 +/- 0.32 vs. 0.73 +/- 0.23, 3.53 +/- 0.46 vs. 1.08 +/- 0.42), and the activity of SOD (U/mg) was significantly lowered (32.80 +/- 3.82 vs. 60.51 +/- 6.81, 33.44 +/- 3.24 vs. 64.19 +/- 6.60), and the expression of caspase-3 mRNA in lung tissue was significantly up-regulated (0.717 +/- 0.037 vs. 0.216 +/- 0.046, 0.744 +/- 0.046 vs. 0.227 +/- 0.037, all P < 0.01). Compared with that of the LIRI group, apoptosis rate of pulmonary cell was significantly decreased [(14.42 +/- 1.61)% vs. (25.60 +/- 3.22)%, (10.02 +/- 1.64)% vs. (26.01 +/- 4.50)%], content of MDA (nmol/mg) was lowered significantly (1.75 +/- 0.33 vs. 3.26 +/- 0.32, 2.15 +/- 0.25 vs. 3.53 +/- 0.46), and activity of SOD (U/mg) was significantly elevated (42.76 +/- 2.06 vs. 32.80 +/- 3.82, 44.94 +/- 3.11 vs. 33.44 +/- 3.24, all P < 0.01) in NAC group. The expression of caspase-3 in lung tissue was remarkably down-regulated compared with that of LIRI group (0.441 +/- 0.038 vs. 0.717 +/- 0.037, 0.410 +/- 0.037 vs. 0.744 +/- 0.046, both P < 0.01). The ultrastructure changes in lung tissue were milder in NAC group than in LIRI group. Positive correlation was found between the expression of caspase-3 and apoptosis rate and the content of MDA (3 hours: r = 0.9036, 0.9216; 6 hours: r = 0.9655, 0.9650, all P < 0.01), but negative correlation was found between apoptosis rate and activity of SOD (3 hours: r = -0.9511, 6 hours: r = - 0.9574, both P < 0.01) after LIRI 3 hours and 6 hours. CONCLUSION: During early period of LIRI, caspase-3 was significantly deregulated by NAC, therefore the cellular apoptosis was inhibited, thus protecting lung tissue from LIRI. PMID- 22316546 TI - [A study of the clinical features and the effect of therapy on acute respiratory distress syndrome patients as a result of severe triphosgene poisoning]. AB - OBJECTIVE: To investigate the clinical features and treatment strategy for acute respiratory distress syndrome (ARDS) caused by phosgene. METHODS: Individualized therapy was carried out in 17 cases of severe phosgene poison patients. Blood routine, electrolytes, blood gas analysis, hepatic and renal function tests and cardiac enzymes were examined before and after treatment. RESULTS: Vital signs, fluid, electrolytes and acid-base disturbances were improved after treatment. As compared to that of pre-treatment period, white blood cells [WBC, *10(9)/L: 12.18 +/- 4.76 vs. 21.93 +/- 6.21], neutrophil percentage (0.87 +/- 0.05 vs. 0.92 +/- 0.03), hemoglobin (Hb, g/L: 128.12 +/- 25.65 vs. 173.71 +/- 23.53), blood platelet count [PLT,*10(9)/L:165.12 +/- 31.70 vs. 254.47 +/- 70.80], alanine transaminase (ALT, U/L: 70.71 +/- 46.70 vs. 212.71 +/- 141.34), aspartate aminotransferase (AST, U/L: 52.47 +/- 34.68 vs. 82.41 +/- 34.60), blood urea nitrogen (BUN, mmol/L: 5.83 +/- 4.09 vs. 7.89 +/- 5.96), serum creatinine (SCr, MUmol/L: 48.13 +/- 14.97 vs. 67.25 +/- 24.29), lactate dehydrogenase (LDH, U/L: 280.10 +/- 81.77 vs. 586.35 +/- 186.71), creatine kinase (CK, U/L: 199.12 +/- 106.75 vs. 683.00 +/- 323.21), MB isoenzyme of creatine kinase (CK-MB, U/L: 26.94 +/- 9.13 vs. 45.59 +/- 11.21), serum chlorine anion [Cl(-), mmol/L: 95.88 +/- 6.06 vs. 102.29 +/- 7.28], respiratory rate (RR, beats/min: 20.88 +/- 4.30 vs. 30.06 +/- 5.78), heart rate (HR, beats/min: 82.76 +/- 17.16 vs. 113.35 +/- 16.90), blood pH value (7.34 +/- 0.44 vs. 7.39 +/- 0.03) were all decreased (P < 0.05 or P < 0.01). Serum sodium ion [Na(+),mmol/L:140.61 +/- 6.69 vs. 134.06 +/- 4.80], arterial partial pressure of oxygen [PO(2), mm Hg, 1 mm Hg = 0.133 kPa: 84.41 +/- 30.58 vs. 59.88 +/- 15.19] and pulse oxygen saturation [SpO(2): 0.91 +/- 0.08 vs. 0.78 +/- 0.15] were increased (P < 0.05 or P < 0.01). Sixteen patients totally recovered, 1 patient died, and the cure rate was 94.12%. CONCLUSIONS: Respiratory system could be mainly injured as the result of exposure to phosgene and leading to ARDS. Early initial combination therapies with corticosteroids and respiratory support should be addressed. PMID- 22316547 TI - Prognostic factors of arthroscopic pull-out repair for a posterior root tear of the medial meniscus. AB - BACKGROUND: Repair of a posterior root tear of the medial meniscus (MRT) decreases peak contact pressure by restoring hoop tension and is expected to prevent progression to osteoarthritis. PURPOSE: The purposes of this study were (1) to report the clinical and magnetic resonance imaging (MRI) results of arthroscopic pull-out repair of the MRT and (2) to identify prognostic factors of poor outcome. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Fifty-one patients (47 women, 4 men) who underwent arthroscopic pull-out repair of the MRT by a single surgeon were enrolled. Mean follow-up after surgery was 33 months (range, 24-44 months). To identify factors affecting final outcome, patient specific factors, such as gender, age, body mass index, meniscus extrusion, extrusion increase, subchondral edema, degree of varus alignment (<5 degrees or >5 degrees ), and cartilage status in the medial compartment (Outerbridge grade 1 or 2 lesion vs grade 3 or 4 lesion), were investigated. Final clinical outcomes were determined using a visual analog scale (VAS) for pain and patient satisfaction scores, American Knee Society (AKS) scores, and Lysholm scores, and MRI outcomes were determined by evaluating meniscus extrusion and articular cartilage status. Multiple regression analysis was performed to identify variables that independently affected clinical and MRI-determined outcomes. RESULTS: All clinical outcome measures significantly improved after surgery. Patients with Outerbridge grade 3 or 4 chondral lesions had poorer results than those with grade 1 or 2 lesions in terms of AKS function and Lysholm scores. Patients with varus alignment of >5 degrees had poorer results than those with varus alignment of <5 degrees in terms of VAS satisfaction, AKS function, and Lysholm scores. Mean meniscus extrusion increased from 3.6 mm preoperatively to 5.0 mm postoperatively. Chondral lesions progressed in 3 (9.7%) of 31 patients. Preoperative meniscus extrusion was found to be positively correlated with final extrusion. CONCLUSION: At a mean follow-up of 33 months after pull-out repair, extrusion of the meniscus was found to have progressed. Nevertheless, this technique provided patients with a clinical benefit. Outerbridge grade 3 or 4 chondral lesions and varus alignment of >5 degrees were found to independently predict an inferior clinical outcome. PMID- 22316548 TI - Return to athletic activity after osteochondral allograft transplantation in the knee. AB - BACKGROUND: Fresh-stored osteochondral allografts have been used successfully to resurface large chondral and osteochondral defects of the knee. However, there are limited data available for the return to athletic activity. PURPOSE: To review the rate of return to athletic activity after osteochondral allograft transplantation in the knee and to identify any potential risk factors for not returning to sport. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Forty-three athletes were treated with fresh-stored osteochondral allograft transplantation for symptomatic large chondral or osteochondral defects of the knee from 2000 to 2010. The average age of the athletes (30 men, 13 women) was 32.9 years (range, 18-49 years). Patients were prospectively evaluated by International Knee Documentation Committee (IKDC), activities of daily living scale of the Knee Injury and Osteoarthritis Outcome Score (KOOS), Marx Activity Rating Scale, and Cincinnati Sports Activity Scale scores. A multivariable regression analysis was performed to identify potential risk factors for failure to return to sport at the preinjury level. RESULTS: At an average 2.5-year follow up, limited return to sport was possible in 38 of 43 athletes (88%), with full return to the preinjury level achieved in 34 of 43 athletes (79%). In these 34 athletes, time to return to sport was 9.6 +/- 3.0 months. Age >=25 years (P = .04) and preoperative duration of symptoms greater than 12 months (odds ratio, 37; P = .003) negatively affected the ability to return to sport. In the athletes who returned to their previous level of competition, IKDC (P < .001), KOOS (P = .02), and Marx Activity Rating Scale (P < .001) scores were all significantly greater than in those athletes who did not return to sport. CONCLUSION: Osteochondral allograft transplantation in an athletic population for chondral and osteochondral defects in the knee allows for a high rate of return to sport. Risk factors for not returning to sport included age >=25 years and preoperative duration of symptoms >=12 months. PMID- 22316549 TI - Comparing outcomes after off-pump coronary artery bypass versus drug-eluting stent in diabetic patients. AB - BACKGROUND: Off-pump coronary artery bypass surgery and sirolimus-eluting stent placement have been widely used for the treatment of coronary artery disease. The goal of this study was to compare long-term outcomes after off-pump coronary artery bypass surgery or sirolimus-eluting stent placement in diabetic patients with multivessel disease. METHODS: This observational study enrolled 350 off-pump coronary artery bypass patients and 143 sirolimus-eluting stent patients receiving care at our institution between 2000 and 2007. All patients had diabetes and multivessel disease including proximal left anterior descending or left main coronary artery. The choice of revascularization (percutaneous coronary intervention versus coronary artery bypass surgery) was left to the physician's discretion rather than randomization. Cox proportional-hazard analyses, adjusting baseline risk factors and propensity score, which predicted the probability of receiving off-pump coronary artery bypass, were conducted to evaluate outcomes, including all-cause mortality, cardiac death, target vessel revascularization, and major adverse cardiac and cerebrovascular events. RESULTS: During the follow up (2.6+/-1.6 years) period, there was no difference between off-pump coronary artery bypass and sirolimus-eluting stent placement in all-cause mortality or cardiac death. However, the incidences of acute coronary syndrome, target vessel revascularization, and major adverse cardiac and cerebrovascular events were markedly lower in the patients undergoing off-pump coronary artery bypass than in those receiving sirolimus-eluting stent placement. CONCLUSION: Off-pump coronary artery bypass is superior to sirolimus-eluting stent placement in terms of acute coronary syndrome, target vessel revascularization, and major adverse cardiac and cerebrovascular events in diabetic patients with multivessel coronary artery disease. PMID- 22316550 TI - Health-related quality of life in children and adults with respiratory allergy in Colombia: prospective study. AB - BACKGROUND: Allergic diseases are very common, with the estimated cumulative prevalence in Colombia for asthma and allergic rhinitis being 22.7% and 31.3% respectively, and with a clear upward trend. A major social as well as economic impact associated with allergic disease has been described. Because in Colombia there are no studies that assess the Health-Related Quality of Life (HRQOL) in allergic respiratory diseases, our aim is to describe the HRQOL in subjects with respiratory allergy and its association with clinical control variables. METHODS: A prospective descriptive study was conducted among 76 Colombian subjects with rhinitis and asthma/allergic rhinitis. In order to evaluate the HRQOL, the instruments Kidscreen-27 and SF-36 were applied. The scores obtained in the HRQOL fields were correlated with the following clinical variables: peak expiratory flow (PEF) and peak nasal inspiratory flow (PNIF). RESULTS: In children, the better HRQL domain is present in the school environment (55.9) and the worst in psychological well-being (39.9). For adults the worst HRQL was found in the emotional function domain (55.6) while the physical function (81.7) had the best. There were no statistical differences between groups of asthma/allergic rhinitis and allergic rhinitis. Subjects with allergic asthma showed a strong correlation between the mental health domain and PEF values (r=-0717, p=0.046). CONCLUSION: Mental health is more affected than physical health in Colombian subjects with respiratory allergy. There was a strong correlation between the mental health domain and the values of PEF in patients with asthma/allergic rhinitis. PMID- 22316551 TI - Survival of Mexican patients with paediatric-onset systemic lupus erythematosus and abnormal electroencephalogram. AB - BACKGROUND: Over the past three decades, there has been a remarkable improvement in the outcome of children diagnosed with systemic lupus erythematosus (SLE). In general, paediatric-onset SLE has been associated with higher mortality rates and more disease damage than adults with SLE. The objective was to determinate the impact of clinical, laboratory, and electroencephalographic findings on survival amongst patients with paediatric-onset SLE. METHODS: Charts of Mexican patients with paediatric-onset SLE diagnosed between 1970 and 2001 were analysed retrospectively; univariate and multivariate analyses were used for analysing associations between clinical and laboratory features and death; Kaplan-Meier tests were used to estimate survival curves. RESULTS: 159 patients were included, 105 were female, with a median age of 12.7 years at diagnosis and a median duration of symptoms prior to diagnosis of 8.4 months. Univariate analysis showed that haematuria, leukocyturia, proteinuria, presence of urine cast, <60% glomerular filtration rate, haemolytic anaemia, and abnormal electroencephalogram, were all poor prognostic factors (p<0.05). Multivariate analysis showed that the presence of proteinuria and abnormal electroencephalograms (p<0.05) were independent factors associated with death. The overall survival rate was 82.9% at five years and 77.4% at ten years upon follow-up. Infection and high disease activity were the most common causes of death. CONCLUSIONS: Survival of paediatric-onset SLE patients was lower compared to that reported for patients in wealthier countries. Amongst the patients who died, the presence of proteinuria and abnormal electroencephalograms were found to be determinant for survival. Infection and activity were the most common causes of death. PMID- 22316552 TI - Clinical outcome of staged versus combined treatment approach of hybrid repair of thoracoabdominal aortic aneurysm with visceral vessel debranching and aortic endograft exclusion. AB - Although visceral vessel debranching and endovascular aneurysm exclusion represents a hybrid treatment approach in patients with thoracoabdominal aortic aneurysm, the effect of timing with regard to the visceral debranching procedure and endovascular aneurysm exclusion in this treatment strategy remains unclear. In this study, the authors analyzed their recent institutional experience of visceral debranching and aneurysm stent-grafting procedures. Specifically, the authors compared the effect of staged (n = 27) versus combined (n = 31) hybrid treatment in patients with complex aortic aneurysms. This study showed a higher incidence of renal insufficiency in patients undergoing a combined hybrid repair than the staged hybrid approach. The possibility of aneurysm rupture may exist in the staged treatment approach if the duration of staged repair is prolonged. The combined hybrid treatment strategy should be performed with caution as it is associated with significantly higher complication rates than the staged hybrid treatment modality. PMID- 22316553 TI - AlCl3 induced (hetero)arylation of 2,3-dichloroquinoxaline: a one-pot synthesis of mono/disubstituted quinoxalines as potential antitubercular agents. AB - A direct and single-step method has been developed for the synthesis of mono and 2,3-disubstituted quinoxalines by using a AlCl(3) induced (hetero)arylation of 2,3-dichloroquinoxaline. Both symmetrical and unsymmetrical 2,3-disubstituted quinoxalines can be prepared conveniently by using this method under appropriate reaction conditions. The reaction proceeds via C-C bond formation and can be utilized for the preparation of a variety of quinoxaline derivatives from readily available starting materials and reagents. The molecular structure of a representative compound was confirmed by single crystal X-ray diffraction study. Some of the compounds synthesized were tested for chorismate mutase inhibitory properties in vitro and one compound showed promising activity representing one of the few examples of chorismate mutase inhibition by a heteroarene based small molecule. PMID- 22316554 TI - Development of live-cell imaging probes for monitoring histone modifications. AB - The combination of histone posttranslational modifications occurring in nucleosomal histones determines the epigenetic code. Histone modifications such as acetylation are dynamically controlled in response to a variety of signals during the cell cycle and differentiation, but they are paradoxically maintained through cell division to impart tissue specific gene expression patterns to progeny. The dynamics of histone modifications in living cells are poorly understood, because of the lack of experimental tools to monitor them in a real time fashion. Recently, FRET-based imaging probes for histone H4 acetylation have been developed, which enabled monitoring of changes in histone acetylation during the cell cycle and drug treatment. Further development of this type of fluorescent probes for other modifications will make it possible to visualize complicated epigenetic regulation in living cells. PMID- 22316555 TI - Synthesis and properties of mRNA cap analogs containing imidodiphosphate moiety- fairly mimicking natural cap structure, yet resistant to enzymatic hydrolysis. AB - We describe synthesis and properties of eight dinucleotide mRNA 5' cap analogs containing imidodiphosphate moiety within 5',5'-tri- or tetraphosphate bridge (NH analogs). The compounds were obtained by coupling an appropriate nucleoside 5' imidodiphosphate with nucleotide P-imidazolide mediated by divalent metal chloride in anhydrous DMF. To evaluate the novel compounds as tools for studying cap-dependent processes, we determined their binding affinities for eukaryotic translation initiation factor 4E, susceptibilities to decapping pyrophosphatase DcpS and, for non-hydrolysable analogs, binding affinities to this enzyme. The results indicate that the O to NH substitution in selected positions of oligophosphate bridge ensures resistance to enzymatic decapping and suggest that interactions of NH-analogs with cap binding proteins fairly mimic interactions of unmodified parent compounds. Finally, we identified NH-analogs as potent inhibitors of cap-dependent translation in cell free system, and evaluated their utility as reagents for obtaining 5' capped mRNAs in vitro to be rather moderate. PMID- 22316556 TI - New fluorescent bile acids: synthesis, chemical characterization, and disastereoselective uptake by Caco-2 cells of 3-deoxy 3-NBD-amino deoxycholic and ursodeoxycholic acid. AB - Deoxycholic acid (DCA), a secondary bile acid (BA), and ursodeoxycholic acid (UDCA), a tertiary BA, cause opposing effects in vivo and in cell suspensions. Fluorescent analogues of DCA and UDCA could help investigate important questions about their cellular interactions and distribution. We have prepared a set of isomeric 3alpha- and 3beta-amino analogues of UDCA and DCA and derivatised these with the discrete fluorophore, 4-nitrobenzo-2-oxa-1,3-diazol (NBD), forming the corresponding four fluorescent adducts. These absorb in the range 465-470 nm and fluoresce at approx. 535 nm. In order to determine the ability of the new fluorescent bile acids to mimic the parents, their uptake was studied using monolayers of Caco-2 cells, which are known to express multiple proteins of the organic anion-transporting peptide (OATP) subfamily of transporters. Cellular uptake was monitored over time at 4 and 37 degrees C to distinguish between passive and active transport. All four BA analogues were taken up but in a strikingly stereo- and structure-specific manner, suggesting highly discriminatory interactions with transporter protein(s). The alpha-analogues of DCA and to a lesser extent UDCA were actively transported, whereas the beta analogues were not. The active transport process was saturable, with Michaelis Menten constants for 3alpha-NBD DCA (5) being K(m)=42.27+/-12.98 MUM and V(max)=2.8 +/- 0.4 nmol/(mg protein*min) and for 3alpha-NBD UDCA (3) K(m)=28.20 +/- 7.45 MUM and V(max)=1.8 +/- 0.2 nmol/(mg protein*min). These fluorescent bile acids are promising agents for investigating questions of bile acid biology and for detection of bile acids and related organic anion transport processes. PMID- 22316557 TI - Sorption of ionized and neutral emerging trace organic compounds onto activated sludge from different wastewater treatment configurations. AB - The objective of this study was to examine sorption of a suite of 19 trace organic contaminants (TOrCs) to activated sludge. Compounds examined in this study included neutral, nonionized TOrCs as well as acidic TOrCs which may carry a negative charge and basic TOrCs which may carry a positive charge at the pH of wastewater. These TOrCs were evaluated to examine how sorptive behavior might differ for TOrCs in different states of charge. Additionally, multiple sludges from geographically and operationally different wastewater treatment plants were studied to elicit how solid-phase characteristics influence TOrC sorption. Characterization of sludge solids from 6 full scale treatment facilities and 3 bench-scale reactors showed no significant difference in fraction organic carbon (f(oc)) and cation exchange capacity (CEC). Sorption experiments demonstrated that sorption of TOrCs also exhibits little variation between these different sludges. Organic carbon normalized partition coefficients (logK(oc)) were determined as a measure of sorption, and were found to correlate well with octanol-water partition coefficients (logK(ow)) for nonionized TOrCs, and logD(ow) for anionic TOrCs where logD(ow) is greater than 2. These data were used to construct a linear free energy relationship (LFER), which was comparable to existing LFERs for sorption onto sludge. No trend in sorption was apparent for the remaining anionic TOrCs or for the cationic TOrCs. These data suggest that predicting sorption to activated sludge based on K(ow) values is a reasonable approach for neutral TOrCs using existing LFERs, but electrostatic (and likely other) interactions may govern the sorptive behavior of the charged organic chemicals to sludge. PMID- 22316558 TI - Lipidomics. AB - PURPOSE OF REVIEW: Lipidomics characterizes the composition of intact lipid molecular species in biological systems and the field has been driven by some spectacular advances in mass spectrometry instrumentation and applications. This review will highlight these advances and outline their recent application to address clinical issues. RECENT FINDINGS: This review first identifies recent advances in lipid detection and analysis by a variety of mass spectrometry techniques, then reviews specific application including stable isotope labelling of lipids, lipid mass spectrometry imaging, data analysis and bioinformatics, and finally presents examples of the application of lipidomics to selected disease states. SUMMARY: Lipidomics so far has been principally concerned with identifying novel methodologies, but recent advances demonstrating applications in diabetes, neurodegenerative diseases, cystic fibrosis and other respiratory diseases clearly indicate the potential usefulness of lipidomics both to generate biomarkers of disease and to probe signalling and metabolic processes. PMID- 22316560 TI - Current world literature. PMID- 22316559 TI - Immunomodulation of microglia by docosahexaenoic acid and eicosapentaenoic acid. AB - PURPOSE OF REVIEW: The omega-3 fatty acids (omega-3 FAs) docosahexaenoic acid and eicosapentaenoic acid are dietary components which have been ascribed many different health benefits. Inflammation is present in, and contributes to, pathological conditions in the central nervous system (CNS). Microglia are the primary cells with immune function in the CNS, and inflammation mediated by activated microglia is present in pathological conditions. In this review, we present and discuss findings on the modulation of microglial activities by omega 3 FAs in vivo as well as in vitro, and propose mechanisms for their effects. RECENT FINDINGS: The majority of studies show that omega-3 FAs have anti inflammatory effects on microglia. However, phagocytosis is an activity associated with inflammation and is increased by omega-3 FAs. This can be understood in the light of recent research on the resolution of inflammation. Resolution is induced by proresolving factors, which are metabolites of omega-3 FAs. Proresolving factors are anti-inflammatory and have been shown to increase phagocytosis. Other mechanisms of the anti-inflammatory actions of omega-3 FAs involve the peroxisome proliferator-activated receptor-gamma, omega-3 FA incorporation into the cell membrane, and inhibition of ion currents. SUMMARY: Immunomodulation by omega-3 FAs is mediated by several pathways that are interconnected and is a potential therapy for disorders in the CNS. PMID- 22316562 TI - [High-risk human papilloma virus associated oropharynx squamous cell carcinomas: clinical, biological implications and therapeutical perspectives]. AB - The infection of the head and neck epithelium by high-risk human papillomaviruses (HPV) is a risk factor for cancer onset and development. The incidence of HPV related head and neck squamous cell carcinoma is currently increasing. These lesions display distinct clinical features. HPV positive patients are often younger and have a smaller history of tobacco smoking and alcohol drinking, but have a history of virus-transmitting sex practices. HPV-related tumours are mainly found in the oropharynx, are more associated to a local lymph node invasion and display a poorly differentiated morphology. Despite these more aggressive features, HPV-positive head and neck squamous cell carcinomas correlate with an improved local control, disease-free and global survival. It is thought that HPV-driven specific biologic abnormalities underlie higher tumour sensitivity to chemotherapeutic drugs and ionizing radiations. The expression of the HPV E6 and E7 oncoproteins induce cell transformation by interfering with cell signalling pathways involved in apoptosis, cell cycle, angiogenesis and induce the overexpression of the CDKN2A gene. Therefore, alternative treatments based on therapies targeting these pathways in combination with radiation dose de escalation could be proposed to HPV-positive patients, if they are properly and reliably identified. PMID- 22316563 TI - [Retroperitoneal necrotising fasciitis]. PMID- 22316564 TI - Cloning, characterization, and expression analysis of a novel BmGDAP1 gene from silkworm, Bombyx mori, involved in cytoplasmic polyhedrosis virus infection. AB - A novel ganglioside-induced differentiation-associated protein 1 gene (BmGDAP1) was first cloned and sequenced from silkworm, Bombyx mori using rapid amplification of cDNA ends (RACE). The full-length cDNA of BmGDAP1 was 1514bp, consisting of a 91bp 5' untranslated region (UTR), a 424bp 3'-UTR and a 999bp open reading frame (ORF). The ORF encoded a polypeptide of 332 amino acids, which possessed a thioredoxin (TRX)-like domain, a glutathione S-transferase-C (GST-C) family domain and a transmembrane segment. Furthermore, quantitative real-time PCR analysis revealed that BmGDAP1 transcripts were mainly presented in the tissues of hemocytes and midgut of silkworm, and its expression level was down regulated in the hemocytes, while up-regulated in the midgut. Therefore, it could be concluded that BmGDAP1 plays an important role in the recognition and immune response of silkworm to BmCPV infection. PMID- 22316565 TI - Effectiveness of six-week psychoeducation program on adherence of patients with bipolar affective disorder. AB - OBJECTIVES: This study examined the effectiveness of a six week psychoeducation program on the adherence of patients with Bipolar Affective Disorder. METHOD: An experimental study was conducted at a mood disorder outpatient clinic in Zonguldak, Turkiye. Participants were randomly assigned to either intervention (n=35) or control groups (n=36). Both groups were given pre-tests and post-tests to measure their adherence. In the psychoeducation group, the psychoeducation program was provided for 2 h/week for six weeks. In the control group, standard care and information were provided. RESULTS: After six weeks, the psychoeducation program significantly improved patients' adherence. The treatment adherence rate of the patients in the intervention group increased from 40.0% (14 patients on pre-test), to 86.7% (26 patients on post-test). Meanwhile, the treatment adherence rate of the control group was 38.9% (14 patients) for the pre-test, and 24.2% (8 patients) for the post-test. CONCLUSION: This controlled trial study demonstrated that a six-week psychoeducation program can be a useful intervention to improve adherence in patients undergoing bipolar affective disorder rehabilitation. More comprehensive mental health outcomes need to be undertaken. Further studies exploring a longer term follow-up are also required. PMID- 22316566 TI - Thermally driven spin transport through a transverse-biased zigzag-edge graphene nanoribbon. AB - In the framework of the Landauer-Buttiker formalism, we investigate coherent spin transport through a transverse-biased magnetic zigzag-edge graphene nanoribbon, with a temperature difference applied between the source and the drain. It is shown that a critical source temperature is needed to generate a spin-polarized current due to the presence of a forbidden transport gap. The magnitude of the obtained spin polarization exceeds 90% in a wide range of source temperatures, and its polarization direction could be changed by reversing the transverse electric field. We also find that, at fixed temperature difference, the spin polarized current undergoes a transition from increasing to decreasing as the source temperature rises, which is attributed to the competition between the excited energy of electrons and the relative temperature difference. Moreover, by modulating the transverse electric field, the source temperature and the width of the ribbon, we can control the device to work well for generating a highly spin polarized current. PMID- 22316567 TI - Treatment response trajectories and antipsychotic medications: examination of up to 18 months of treatment in the CATIE chronic schizophrenia trial. AB - BACKGROUND: Trajectory studies highlight heterogeneity in treatment response, although they are yet to systematically differentiate between antipsychotic medications. AIMS: To compare treatment response trajectories across antipsychotic medication groups. METHOD: Data were analyzed from Phase 1 of CATIE, an 18-month double-blind randomized controlled trial of chronic schizophrenia. Change on recurrent Positive and Negative Syndrome Scale (PANSS) administrations for 1124 patients was used to index treatment response trajectories up to 18 months. Trajectory groups were identified with mixed-mode latent class regression modeling. Groups were derived for all participants, and separately for completers, dropouts, and each antipsychotic medication (olanzapine, perphenazine, quetiapine, risperidone, ziprasidone) and then characterized. RESULTS: Trajectory analysis of the entire sample identified that 18.9% of participants belonged to a group of responders. This figure increased to 31.5% for completers, and fell to 14.5% for dropouts. Olanzapine treated patients were significantly more likely than other treatment groups to belong to the trajectory of responders (n=69, 32.55%; Chi=20.13, df=2, p<.01). Separate trajectory analyses of each medication group showed that all medication groups showed two trajectories except olanzapine that had three trajectories and the only trajectory that attained a 20% PANSS reduction by endpoint. CONCLUSIONS: Trajectories of treatment response differ between antipsychotic medications and demonstrate substantial heterogeneity in chronic schizophrenia. PMID- 22316568 TI - Negative symptoms have greater impact on functioning than positive symptoms in schizophrenia: analysis of CATIE data. AB - Increased attention has been given to treatment of negative symptoms and its potential impact on functional outcomes, however previous inferences have been confounded by the fact that measures of functional outcomes often use items similar to those of negative symptoms. We attempted to discern the relative effects of negative symptoms on functioning, as compared to other symptoms, using data from the National Institute of Mental Health CATIE trial of chronic schizophrenia (n=1447) by examining correlations of Positive and Negative Syndrome Scale factors, Calgary Depression Rating Scale and select items from Heinrich's and Lehman's Quality of Life Scales measuring aspects of functioning that did not overlap with negative symptoms. Baseline functioning and change in functioning were more strongly related to PANSS negative factor than any of the other symptoms - though the amount of variance explained by symptom changes in general was small. The data suggests that improvement in negative symptoms may have a distinctive and independent effect on functional outcome relative to other symptoms. This should be further tested in studies where negative symptoms improve without concomitant improvement of other symptoms. PMID- 22316569 TI - Cerium, chitosan and hamamelitannin as novel biofilm inhibitors? AB - OBJECTIVES: The colonization of indwelling medical devices and subsequent biofilm formation represents a global challenge since it promotes the persistence of infection and contributes to antimicrobial resistance. The aim of this study was to determine the antimicrobial activity of cerium, chitosan and hamamelitannin against usual microbial colonizers and to assess their efficacy regarding biofilm formation on polyurethane (PUR)-like catheters. METHODS: The antimicrobial and anti-biofilm effect of cerium nitrate, low molecular weight chitosan (LMWC) and hamamelitannin was tested against Staphylococcus epidermidis, Staphylococcus aureus, Acinetobacter baumannii and Candida albicans strains. Biofilm formation was assessed with PUR-like catheter segments and the metabolic activity was quantified by colorimetry with a tetrazolium reduction assay. RESULTS: Cerium nitrate and LMWC inhibited the microbial growth of all microbial strains tested; hamamelitannin showed no inhibition. Regarding biofilm formation on PUR-like catheters, with subinhibitory concentrations: cerium nitrate significantly inhibited the metabolic activity of C. albicans; LMWC reduced the metabolic activity of S. epidermidis and C. albicans; and hamamelitannin decreased the metabolic activity of all tested bacteria, but not of yeasts. CONCLUSIONS: The microbicidal activity of cerium nitrate and LMWC was clearly demonstrated in this study, as was their fungistatic effect at lower concentrations. Hamamelitannin significantly reduced biofilm metabolic activity of all tested bacteria. These microbial inhibitors may play a promising role regarding different biomedical applications. PMID- 22316570 TI - Comment on: Ethical dilemmas in antibiotic treatment. PMID- 22316571 TI - Lopinavir/ritonavir significantly influences pharmacokinetic exposure of artemether/lumefantrine in HIV-infected Ugandan adults. AB - BACKGROUND: Treatment of HIV/malaria-coinfected patients with antiretroviral therapy (ART) and artemisinin-based combination therapy has potential for drug interactions. We investigated the pharmacokinetics of artemether, dihydroartemisinin and lumefantrine after administration of a single dose of 80/480 mg of artemether/lumefantrine to HIV-infected adults, taken with and without lopinavir/ritonavir. METHODS: A two-arm parallel study of 13 HIV-infected ART-naive adults and 16 HIV-infected adults stable on 400/100 mg of lopinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors (ClinicalTrials.gov, NCT 00619944). Each participant received a single dose of 80/480 mg of artemether/lumefantrine under continuous cardiac function monitoring. Plasma concentrations of artemether, dihydroartemisinin and lumefantrine were measured. RESULTS: Co-administration of artemether/lumefantrine with lopinavir/ritonavir significantly reduced artemether maximum concentration (C(max)) and area under the concentration-time curve (AUC) [median (range): 112 (20-362) versus 56 (17-236) ng/mL, P = 0.03; and 264 (92-1129) versus 151 (38 606) ng . h/mL, P < 0.01]. Dihydroartemisinin C(max) and AUC were not affected [66 (10-111) versus 73 (31-224) ng/mL, P = 0.55; and 213 (68-343) versus 175 (118 262) ng . h/mL P = 0.27]. Lumefantrine C(max) and AUC increased during co administration [2532 (1071-5957) versus 7097 (2396-9462) ng/mL, P < 0.01; and 41,119 (12,850-125,200) versus 199,678 (71,205-251,015) ng . h/mL, P < 0.01]. CONCLUSIONS: Co-administration of artemether/lumefantrine with lopinavir/ritonavir significantly increases lumefantrine exposure, but decreases artemether exposure. Population pharmacokinetic and pharmacodynamic trials will be highly valuable in evaluating the clinical significance of this interaction and determining whether dosage modifications are indicated. PMID- 22316572 TI - High phenotypic plasticity of Suaeda maritima observed under hypoxic conditions in relation to its physiological basis. AB - BACKGROUND AND AIMS: Phenotypic plasticity, the potential of specific traits of a genotype to respond to different environmental conditions, is an important adaptive mechanism for minimizing potentially adverse effects of environmental fluctuations in space and time. Suaeda maritima shows morphologically different forms on high and low areas of the same salt marsh. Our aims were to examine whether these phenotypic differences occurred as a result of plastic responses to the environment. Soil redox state, indicative of oxygen supply, was examined as a factor causing the observed morphological and physiological differences. METHODS: Reciprocal transplantation of seedlings was carried out between high and low marsh sites on a salt marsh and in simulated tidal-flow tanks in a glasshouse. Plants from the same seed source were grown in aerated or hypoxic solution, and roots were assayed for lactate dehydrogenase (LDH) and alcohol dehydrogenase, and changes in their proteome. KEY RESULTS: Transplanted (away) seedlings and those that remained in their home position developed the morphology characteristic of the home or away site. Shoot Na(+), Cl(-) and K(+) concentrations were significantly different in plants in the high and low marsh sites, but with no significant difference between home and away plants at each site. High LDH activity in roots of plants grown in aeration and in hypoxia indicated pre adaptation to fluctuating root aeration and could be a factor in the phenotypic plasticity and growth of S. maritima over the full tidal range of the salt marsh environment. Twenty-six proteins were upregulated under hypoxic conditions. CONCLUSIONS: Plasticity of morphological traits for growth form at extremes of the soil oxygenation spectrum of the tidal salt marsh did not correlate with the lack of physiological plasticity in the constitutively high LDH found in the roots. PMID- 22316573 TI - Danish heart patients' participation in and experience with rehabilitation. AB - AIM: This study investigated the proportion of Danish patients in cardiac therapy for ischaemic heart disease who participated in cardiac rehabilitation. The study examined differences in patients' participation in and experience and satisfaction with cardiac rehabilitation. METHODS: Data were obtained from a postal questionnaire in a representative sample of patients in therapy for an ischaemic heart disease. Response data were tabulated and analysed by logistic regression. RESULTS: 3% of the patients participated in a complete rehabilitation programme according to Danish standards, 47% of the patients participated in a partial rehabilitation programme, and additionally 32% of the patients participated in a very limited rehabilitation programme. The number of patients participating in a complete rehabilitation programme was low due to the fact that only few patients (and their relatives) received psychological support. The factors living alone and low education are associated with low participation and in particular with receiving psychological support. Elderly (>=50 years) and male patients showed higher satisfaction scores. Patients receiving psychosocial elements in their rehabilitation programme reported higher satisfaction with their rehabilitation. CONCLUSIONS: Few Danish patients with ischaemic heart disease participate in a complete rehabilitation programme mainly due to psychosocial elements not yet being an integral part of cardiac rehabilitation in Denmark. There is a need to differentiate and tailor cardiac rehabilitation to different patient segments, e.g. by gender and age. PMID- 22316575 TI - The role of psychomotor activation in discriminating unipolar from bipolar disorders: a classification-tree analysis. AB - OBJECTIVE: Multiple studies indicate that bipolar disorders are often underrecognized, misdiagnosed, and incorrectly treated. The aim of the present report is to determine which combination of clinical, demographic, and psychopathological factors and corresponding cutoff scores best discriminate patients with unipolar disorder from those with bipolar disorders. METHOD: The study sample includes outpatients and inpatients (N = 1,158) participating in 5 studies carried out in the United States and Italy between October 2001 and March 2008, one of which was a randomized clinical trial. Diagnostic assessment was carried out with the SCID, which allows diagnoses to be made according to DSM-IV TR criteria. Using an exploratory statistical approach based on a classification tree, we employed 5 mania spectrum factors and 6 depression spectrum factors derived from the Mood Spectrum Self-Report Instrument (MOODS-SR) in combination with demographic and clinical characteristics to discriminate participants with unipolar versus bipolar disorders. RESULTS: The psychomotor activation factor, assessing the presence of thought acceleration, distractibility, hyperactivity, and restlessness for 1 or more periods of at least 3 to 5 days in the lifetime, identified subgroups with an increasing likelihood of bipolar disorder diagnosis. Mixed instability and suicidality contributed to further subtyping the sample into mutually exclusive groups, characterized by a different likelihood of receiving a diagnosis of bipolar disorder. Of the demographic and clinical characteristics included in the analysis, only sex proved to be useful to improve the discrimination. CONCLUSIONS: The psychomotor activation factor proved to be the most potent discriminator of those with unipolar versus bipolar diagnoses. The items that constitute this factor, together with those that constitute the mixed instability, suicidality, and euphoria factors, might be useful in making the differential diagnosis. PMID- 22316576 TI - Making lemonade out of lemons: a case report and literature review of external pressure as an intervention with pregnant and parenting substance-using women. PMID- 22316577 TI - Questions raised by the failure of a trial of short-term psychodynamic therapy versus pharmacotherapy for major depressive disorder. PMID- 22316578 TI - Depression in older adults: is there another reason to worry? PMID- 22316579 TI - Propranolol, traumatic memories, and amnesia: a study of 36 cases. PMID- 22316580 TI - Using adjunctive treatments when first-line antidepressants fail. AB - Treatment-resistant depression is a common challenge for clinicians, as the majority of patients with depression do not achieve remission after an initial antidepressant trial. Major strategies for managing treatment-resistant depression include switching to another antidepressant or augmenting the initial antidepressant with another medication. Switching may be appropriate for patients experiencing little or no symptom relief or intolerable side effects with the initial antidepressant. For patients who experience partial response from the first-line antidepressant, adjunctive therapies avoid the loss of this response and the wash-out and cross-titration that are required when switching antidepressants. Several effective antidepressant augmentation agents are available, including lithium, thyroid hormone, anti-anxiety medications, and atypical antipsychotics. The evidence for the efficacy and risks of these strategies is discussed. PMID- 22316581 TI - Identifying, diagnosing, and managing ADHD in college students. AB - The prevalence of attention-deficit/hyperactivity disorder (ADHD) on college campuses has increased recently, and clinicians need to be able to identify and treat this condition in this population. In this CME activity, answer multiple choice questions to assess your current knowledge and practice of diagnosing and managing ADHD in college students. PMID- 22316582 TI - Diagnosing and managing patients with dementia. AB - As the number of older Americans grows, the prevalence of dementia is increasing. Older patients who present to primary care offices often have some form of dementia, but various factors can cause the diagnosis to be missed or delayed. Physicians can work to proactively assess dementia in their patients and provide a timely diagnosis. The diagnostic process for dementia includes screening for pathology and, when indicated, conducting a cognitive evaluation and performing a differential diagnosis. Several brief but reliable tools are available to aid in screening and evaluating patients for dementia. PMID- 22316583 TI - Assessing and measuring nonresponse in schizophrenia. AB - Symptom resolution, relapse prevention, and recovery of function are the goals of schizophrenia treatment. Often, clinicians rely on clinical impressions and informal interviews to judge whether treatment strategies are achieving these goals. However, measurement-based rating scales can assist clinicians in diagnosing patients, as well as in assessing their treatment response, evaluating the tolerability of adverse effects, and documenting the efficacy of treatment trials. Evaluating early treatment response or nonresponse can help clinicians in formulating long-term strategies to help patients achieve optimal outcomes. PMID- 22316584 TI - The course of chronic pain with and without psychiatric disorders: a 6-year follow-up study from childhood to adolescence and young adulthood. AB - OBJECTIVE: Psychiatric disorders are common in children with chronic pain, but their course and impact when children grow up are unknown. This study examines the 6-year clinical outcome of children referred for chronic pain with and without comorbid psychiatric disorders. METHOD: In 91 children and adolescents (aged 8 to 17 years) referred to a university outpatient clinic for chronic pain, child psychiatric disorders were assessed using the Diagnostic Interview Schedule for Children-parent version (DISC-P) between 2000 and 2002. Participants (aged 13 to 24 years) were reassessed on average 6-years later. Outcome measures were chronic pain and psychiatric disorders assessed with the Diagnostic Interview Schedule for Children-children version (DISC-C) or the Composite International Diagnostic Interview (CIDI) and Diagnostic Interview Schedule IV (DIS). RESULTS: After 6 years, 75% of the participants still experienced chronic pain and 15% were in complete remission of both chronic pain and psychiatric disorder. The prevalence of psychiatric disorders (both persistent and new onset disorders) at follow-up was 32%. Baseline psychiatric disorder was a predictor of psychiatric disorder at follow-up (OR = 2.6, 95% CI = 1.1-6.5, P = .04; adjusted OR = 2.8, 95% CI = 1.1-7.1, P = .03) but did not predict persistence of chronic pain. CONCLUSIONS: Children referred for chronic pain frequently continue to suffer from chronic pain and psychiatric disorders in adolescence and young adulthood. In this population, comorbid psychiatric disorder at study entry was a predictor of psychiatric disorder, but not of persistent chronic pain, in adolescence and young adulthood. PMID- 22316585 TI - Detection of bacterial 16S ribosomal RNA genes for forensic identification of vaginal fluid. AB - To preliminarily evaluate the applicability of bacterial DNA as a marker for the forensic identification of vaginal fluid, we developed and performed PCR-based detection of 16S ribosomal RNA genes of Lactobacillus spp. dominating the vagina and of bacterial vaginosis-related bacteria from DNA extracted from body fluids and stains. As a result, 16S ribosomal RNA genes of Lactobacillus crispatus, Lactobacillus jensenii and Atopobium vaginae were specifically detected in vaginal fluid and female urine samples. Bacterial genes detected in female urine might have originated from contaminated vaginal fluid. In addition, those of Lactobacillus iners, Lactobacillus gasseri and Gardnerella vaginalis were also detected in non-vaginal body fluids such as semen. Because bacterial genes were successfully amplified in DNA samples extracted by using the general procedure for animal tissues without any optional treatments, DNA samples prepared for the identification of vaginal fluid can also be used for personal identification. In conclusion, 16S ribosomal RNA genes of L. crispatus, L. jensenii and A. vaginae could be effective markers for forensic identification of vaginal fluid. PMID- 22316586 TI - Monte-Carlo simulations of the new LNHB manganese bath facility. AB - The new manganese bath facility of the Laboratoire National Henri Becquerel has been modeled by using three Monte-Carlo codes: MCNPX, GEANT4, and FLUKA, in order to determine the correction factors needed in the neutron source calibration process. The most realistic source geometry has been determined, and the most reliable cross sections library has been chosen. The models were compared, and discrepancies between the codes have been pointed out. Potential causes of deviations between results were assessed and discussed using additional models. Finally, an experimental process is proposed to validate the accuracy of the different codes and their abilities in simulating the neutron capture by the manganese bath. PMID- 22316587 TI - Tillandsia usneoides L, a biomonitor in the determination of Ce, La and Sm by neutron activation analysis in an industrial corridor in Central Mexico. AB - The atmosphere of the Tula Industrial Corridor in Central Mexico is contaminated due to several industries including oil refining while station monitoring in this area are limited. Lanthanides are considered fingerprint of oil refinery activities, and La, Ce and Sm have been previously detected in this area using filters. The suitability of T. usneoides as a biomonitor assessing the La, Ce and Sm concentrations in Particulate Matter is evaluated by NAA. Results of both biomonitor and filters are highly correlated. PMID- 22316588 TI - Photolytic and photocatalytic degradation of quinclorac in ultrapure and paddy field water: identification of transformation products and pathways. AB - Quinclorac (QNC) is an effective but rather persistent herbicide commonly used in rice production. This herbicide presents a mean persistence in the environment so its residues are considered of environmental relevance. However, few studies have been conducted to investigate its environmental behavior and degradation. In the present work, direct photolysis and TiO(2) photocatalysis of the target compound in ultrapure and paddy field water were investigated. After 10h photolysis in ultrapure water, the concentration of QNC declined 26% and 54% at 250 and 700 W m(-2), respectively. However, the amount of quinclorac in paddy field water remained almost constant under the same irradiation conditions. QNC dissipated completely after 40 min of TiO(2) photocatalysis in ultrapure water, whereas 130 min were necessary to degrade 98% of the initial concentration in paddy field water. Possible QNC photolytic and photocatalytic degradation pathways are proposed after structure elucidation of the main transformation products, through liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry and exact mass measurements. Pyridine ring hydroxylation at C-9 followed by ring opening and/or oxidative dechlorination were the key steps of QNC degradation. PMID- 22316589 TI - Atmospheric mercury pollution at an urban site in central Taiwan: mercury emission sources at ground level. AB - Total gaseous mercury (Hg) (TGM), gaseous oxidized Hg (GOM), and particulate bound Hg (PBM) concentrations and dry depositions were measured at an urban site in central Taiwan. The concentrations were 6.14+/-3.91 ng m(-3), 332+/-153, and 71.1+/-46.1 pg m(-3), respectively. These results demonstrate high Hg pollution at the ground level in Taiwan. A back trajectory plot shows the sources of the high TGM concentration were in the low atmosphere (<500 m) and approximately 50% of the air masses coming from upper troposphere (>500 m) were associated with low TGM concentrations. This finding implies that Hg is trapped in the low atmosphere and comes from local Hg emission sources. The conditional probability function (CPF) reveals that the plumes of high TGM concentrations come from the south and northwest of the site. The plume from the south comes from two municipal solid waste incinerators (MSWIs). However, no significant Hg point source is located to the northwest of the site; therefore, the plumes from the northwest are hypothesized to be related to the combustion of agricultural waste. Dry deposition fluxes of Hg measured at this site considerably exceeded those measured in North America. Overall, this area is regarded as a highly Hg contaminated area because of local Hg emission sources. PMID- 22316590 TI - Diffusion-weighted imaging versus superparamagnetic iron oxide (SPIO)-enhanced MRI: exclusive and combined values in the assessment of hepatic metastases. AB - PURPOSE: The purpose was to validate diffusion-weighted imaging (DWI) in the assessment of hepatic metastases compared with superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging. MATERIALS AND METHODS: For 21 consecutive patients with 160 metastases from extrahepatic malignancy and 25 benign focal lesions, two radiologists evaluated four separate review sessions (I, SPIO-enhanced T2-weighted images; II, precontrast DWI; III, SPIO-enhanced T2 weighted images and precontrast DWI; IV, SPIO-enhanced T2-weighted images plus precontrast and SPIO-enhanced DWI) and assigned confidence levels using a five grade scale for each hepatic lesion. RESULTS: The A(z) values after receiver operating characteristic curve analysis for Reader 1 and Reader 2 were 0.80 and 0.75 on session I, 0.91 and 0.91 on session II, 0.97 and 0.96 on session III and 0.96 and 0.96 on session IV, respectively. The A(z) value of session II was significantly higher than that of session I (Reader 1, P=.004; Reader 2, P<.001), and that of session III was significantly higher than that of session I (P<.001 for each reader) or session II (Reader 1, P=.004; Reader 2, P=.003). Although there was no significant difference of A(z) value between session III and session IV (Reader 1, P=.231; Reader 2, P=.878), the sensitivity improved for session IV compared with that for session III (Reader 1, P=.031; Reader 2, P=.039). CONCLUSION: In the assessment of hepatic metastases, DWI can provide more accurate information than can SPIO-enhanced images. Diagnostic accuracy can be increased even more through the combination of both techniques. PMID- 22316591 TI - Correction of chemical shift misregistration by images from two different bandwidths. AB - One major effect caused by the different chemical shift frequencies of water and fat is the misregistration between the two components in MR images. Methods to correct misregistration are required in clinical MRI for accurate localization and artifact reduction. One of the methods uses the images scanned at opposite readout gradients to separate water and fat signal in the k-space. Its signal-to noise ratio (SNR) achieves maximum when misregistration is around 0.9 pixels and deteriorates rapidly as the misregistration gets larger. In this work, we proposed a method to correct the chemical shift misregistration by using two data sets acquired at two different bandwidths. It is more generalized and flexible than the former method of opposite readout gradients and covers the former one as a special case. In both simulation and experiment, the new method is proved to be capable of correcting large chemical shift misregistration and maintain a good SNR. PMID- 22316592 TI - The utility of cardiac CT beyond the assessment of suspected coronary artery disease. AB - Extensive work has been done over recent years to improve the spatial and temporal resolution of electrocardiogram (ECG)-gated cardiac computed tomography (CT). Advances in both hardware and software analysis have enabled the development of non-invasive coronary angiography. However, these high-quality examinations lend themselves to multiple additional applications beyond coronary angiography. In this review, we illustrate and discuss some established and some emerging applications of ECG-gated cardiac CT beyond the assessment of suspected coronary disease, particularly in light of recent recommendations on the appropriate use of this technology. PMID- 22316593 TI - Apparent diffusion coefficient values of necrotic and solid portion of lymph nodes: differential diagnostic value in cervical lymphadenopathy. AB - AIM: To evaluate whether the analysis of the apparent diffusion coefficient (ADC) values of the necrotic and solid portions of lymph nodes aids differentiation between the causes of cervical lymphadenopathy. MATERIALS AND METHODS: Thirty-six patients with cervical lymph node metastasis from head and neck squamous cell carcinomas (SCC), 19 patients with lymphoma, and 23 patients with tuberculous lymphadenitis underwent conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI). The ADC values of necrotic and solid portions of lymph nodes were measured and compared. Receiver operating characteristic (ROC) analysis was employed to investigate whether ADC values could help to discriminate between the causes of cervical lymphadenopathy, and to obtain the optimal ADC threshold values. RESULTS: The mean ADC values of the solid portions of metastatic nodes, lymphomatous nodes, and tuberculous nodes were (0.93+/ 0.16)*10(-3)mm(2)/s, (0.64+/-0.13)*10(-3)mm(2)/s and (1.01+/-0.11)*10(-3)mm(2)/s, respectively (p<0.01). The mean ADC values of necrosis of metastatic and tuberculous nodes were (2.02+/-0.36)*10(-3)mm(2)/s and (1.25+/-0.15)*10( 3)mm(2)/s (p<0.01). By using the ADC value of the solid portion, the optimal ADC threshold values for distinguishing between metastasis and lymphoma, between metastasis and tuberculosis, and between lymphoma and tuberculosis were 0.77*10( 3), 0.98*10(-3) and 0.81*10(-3)mm(2)/s, respectively, and the sensitivities and specificities were 83 and 89%, 70 and 68%, 93 and 100%, respectively. By using ADC values of necrosis, the optimal ADC threshold value for distinguishing between metastasis and tuberculosis was 1.59*10(-3)mm(2)/s, and the sensitivity and specificity were 88 and 100%, respectively. CONCLUSION: The ADC values both of the necrotic and solid portions of the lymph nodes are useful in differentiation between the causes of cervical lymphadenopathy. The ADC value of necrosis is especially helpful in discriminating metastasis from tuberculosis. PMID- 22316594 TI - In vivo proton MRS of normal pancreas metabolites during breath-holding and free breathing. PMID- 22316595 TI - Quantitative assessment of pure aortic valve regurgitation with dual-source CT. AB - AIM: To assess the severity of pure aortic regurgitation by measuring regurgitation volumes (RV) and fractions (RF) with dual-source computed tomography (DSCT) as compared to magnetic resonance imaging (MRI) and echocardiography. MATERIALS AND METHODS: Thirty-eight patients (15 men, 23 women; mean age 46+/-11 years) with isolated aortic valve regurgitation underwent retrospectively electrocardiogram (ECG)-gated DSCT, echocardiography, and MRI. Stroke volumes of the left and right ventricles were measured at DSCT and MRI. Thus, RVs and RFs were calculated and compared. The agreement between DSCT and MRI was tested by intraclass correlation coefficient and Bland-Altman analyses. Spearman's rank order correlation and weighted kappa tests were used for testing correlations of AR severity between DSCT results and corresponding echocardiographic grades. RESULTS: The RV and RF measured by DSCT were not significantly different from those measured using MRI (p=0.71 and 0.79). DSCT correlated well with MRI for the measurement of RV (r(I)=0.86, p<0.001) and calculation of the RF (r(I) =0.90, p<0.001). Good agreement between the techniques was obtained by using Bland-Altman analyses. The severity of regurgitation estimated by echocardiography correlated well with DSCT (r(s)=0.95, p<0.001) and MRI (r(s)=0.95, p<0.001). Inter-technique agreement between DSCT and two-dimensional transthoracic echocardiography (2DTTE) regarding the grading of the severity of AR was excellent (kappa=0.90), and good agreement was also obtained between MRI and 2DTTE assessments of the severity of AR (kappa=0.87). CONCLUSION: DSCT using a volume approach can be used to quantitatively determine the severity of pure aortic regurgitation when compared with MRI and echocardiography. PMID- 22316596 TI - Phase-contrast MRI and applications in congenital heart disease. AB - A review of phase-contrast magnetic resonance imaging techniques, with specific application to congenital heart disease, is presented. Theory, pitfalls, advantages, and specific examples of multiple, well-described congenital heart disease presentations are discussed. PMID- 22316597 TI - In vivo proton MRS of normal pancreas metabolites during breath-holding and free breathing. AB - AIM: To characterize normal pancreas metabolites using in vivo proton magnetic resonance spectroscopy ((1)H MRS) at 3T under conditions of breath-holding and free-breathing. MATERIALS AND METHODS: The pancreases of 32 healthy volunteers were examined using (1)H MRS during breath-holding and free-breathing acquisitions in a single-voxel point-resolved selective spectroscopy sequence (PRESS) technique using a 3T MRI system. Resonances were compared between paired spectra of the two breathing modes. Furthermore, correlations between lipid (Lip) content and age, body-mass index (BMI), as well as choline (Cho) peak visibility of the normal pancreas were analysed during breath-holding. RESULTS: Twenty-nine pairs of spectra were successfully obtained showing three major resonances, Lip, Cho, cholesterol and the unsaturated parts of the olefinic region of fatty acids (Chol+Unsat). Breath-hold spectra were generally better, with higher signal-to noise ratios (SNR; Z=-2.646, p=0.008) and Cho peak visible status (Z=-2.449, p=0.014). Correlations were significant between spectra acquired by the two breathing modes, especially for Lip height, Lip area, and the area of other peaks at 1.9-4.1ppm. However, the Lip resonance was significantly different between the spectra of the two breathing modes (p<0.05). In the breath-holding spectra, there were significant positive correlations between Lip peak height, area, and age (r=0.491 and 0.521, p=0.007 and 0.004), but not between Lip peak area and BMI. There was no statistical difference in Cho resonances between males and females. The Lip peak height and area were significantly higher in the Cho peak invisible group than in the Cho peak visible group (t=2.661 and 2.353, p=0.030 and 0.043). CONCLUSION: In vivo(1)H MRS of the normal pancreas at 3T is technically feasible and can characterize several metabolites. (1)H MRS during breath-holding acquisition is superior to that during free-breathing acquisition. PMID- 22316598 TI - Characteristics of venous insufficiency in western Turkey: VEYT-I study. AB - OBJECTIVES: Syndromes of venous hypertension and reduced venous clearance are important causes of morbidity and disability in patients with varicose venous disease. Published estimates of the prevalence of varicosities range from 7% to 55% in the adult population, with most studies demonstrating clinical varicose reflux in about 40% of the population where the frequency of venous insufficiency is believed to be higher in Westernized and industrialized nations, most likely due to differences in lifestyle and activity. Unfortunately, the prevalence in a Turkish population is not known. The goal of the VEYT-I study was to determine the characteristics of venous insufficiency in a Turkish population. METHOD: Randomized patients who applied to a health-care centre were included in this study. The Tubingen questionnaire was used to evaluate the signs and symptoms of venous insufficiency and their seriousness in a Turkish population. Patients were additionally questioned on demographic data, education, working, living habits, quality of life and actual health status. RESULTS: A total of 2167 patients were involved in this study. Four patients with chronic renal failure and 40 patients with congestive heart failure were excluded. In patients with venous insufficiency, 90.1% did not receive any therapy. In all, 51.53% of patients with venous insufficiency were men, and mean age was 56.9 +/- 9.4. CONCLUSION: The prevalence of venous insufficiency seems to be somewhat higher when compared with Western populations. One of the most prominent facts is that about 90% of patients with venous insufficiency did not receive any therapy. Therefore, disease-related complications or discomfort might emerge soon, and so more importance should be given to venous insufficiency. The VEYT-I study is a continuing database study and the target is to enlarge the study population. PMID- 22316599 TI - Role of injection pressure, flow and sclerosant viscosity in causing cutaneous ulceration during sclerotherapy. AB - The objective of the study is to evaluate the viscosity of popular sclerosants and their flow hydrodynamics through a syringe/needle to further discuss Miyake's old, venous-capillary reflux theory, using additional objective data. The following sclerosing agents were tested in the study: 75% dextrose (D75%); 50% dextrose (D50%); 5% ethanolamine oleate (Etha5%); 0.5% laureth-9 (Aet0.5%) and 0.1% sodium tetradecyl sulphate (STS0.1%). Using 5 mL syringes and 27G needles, the resulting pressures and flows for each sclerosant agent were measured. To do this, a three-way stopcock was connected between the syringe and the needle so that an arm of the stopcock could be used to measure injection pressures with a digital monitor in 1 mmHg increments. Two trials were performed: in trial 1, the syringe was attached to a Samtronic 680 infusion pump and in trial 2, the solutions were injected manually. The observed sclerosant viscosities were as follows: D75%: 0.28 Poise; D50%: 0.12 Poise; Etha5%: 0.10 Poise; Aet0.5%: 0.07 Poise; and STS0.1%: 0.04 Poise. In trial 1 (constant flow), it was observed that D75%, which had the highest viscosity of the sclerosants tested, had the highest pressure readings. In trial 2 (constant pressure), the flow obtained with the D75% solution was lower than the flow of the other solutions. In conclusion, based on the rabbit study theory, vessel size and sclerosant viscosity and strength, not extravasation, play a role in causing ulceration from injection sclerotherapy. As a result, they all affect the potential of venous-capillary reflux being caused by sclerotherapy injection and, thus, the risk of postsclerotherapeutic cutaneous ulceration. PMID- 22316600 TI - Detection of varicose vein recurrence by duplex ultrasound: intra- and interobserver reproducibility. AB - In a long-term follow-up study comparing saphenofemoral ligation and stripping with endovenous laser ablation, the groin is examined yearly by duplex ultrasound (DUS) to detect postoperative varicose vein recurrence. Clear criteria are needed for the uniformity of DUS observations. Physicians taking care of the follow-up were evaluated by an intra- and interobserver analysis. DUS films of 22 patients with no recurrence and 22 patients with recurrence of varicose veins were twice interpreted in two sessions. Observations were analysed by a kappa test. Interpretations of DUS by experienced observers show a kappa >7. Improved kappa results were measured over time in our physician in training. In conclusion, the reproducibility of DUS studies performed by the experienced observers of the study is excellent. PMID- 22316601 TI - Cartilaginous metaplasia of varicose veins: a case report. AB - Cartilaginous metaplasia of superficial veins was found in a 64-year-old woman who underwent surgery for varicose veins. At operation, some varicose veins of the medial thigh were semi-rigid and fibroelastic to the touch. Histology revealed that half the lumen was occupied by chondroid tissue. The other half was obliterated by fibrous tissue, typical of post-thrombotic involution. Possible causes of cartilaginous metaplasia are briefly discussed. PMID- 22316602 TI - Constitutive expression of a barley Fe phytosiderophore transporter increases alkaline soil tolerance and results in iron partitioning between vegetative and storage tissues under stress. AB - Cereals have evolved chelation systems to mobilize insoluble iron in the soil, but in rice this process is rather inefficient, making the crop highly susceptible to alkaline soils. We therefore engineered rice to express the barley iron-phytosiderophore transporter (HvYS1), which enables barley plants to take up iron from alkaline soils. A representative transgenic rice line was grown in standard (pH 5.5) or alkaline soil (pH 8.5) to evaluate alkaline tolerance and iron mobilization. Transgenic plants developed secondary tillers and set seeds when grown in standard soil although iron concentration remained similar in leaves and seeds compared to wild type. However, when grown in alkaline soil transgenic plants exhibited enhanced growth, yield and iron concentration in leaves compared to the wild type plants which were severely stunted. Transgenic plants took up iron more efficiently from alkaline soil compared to wild type, indicating an enhanced capacity to increase iron mobility ex situ. Interestingly, all the additional iron accumulated in vegetative tissues, i.e. there was no difference in iron concentration in the seeds of wild type and transgenic plants. Our data suggest that iron uptake from the rhizosphere can be enhanced through expression of HvYS1 and confirm the operation of a partitioning mechanism that diverts iron to leaves rather than seeds, under stress. PMID- 22316604 TI - Glioblastoma stem-like cell lines with either maintenance or loss of high-level EGFR amplification, generated via modulation of ligand concentration. AB - PURPOSE: Despite the high incidence of epidermal growth factor receptor (EGFR) gene amplification and rearrangement in glioblastomas, no suitable cell line exists that preserves these alterations in vitro and is tumorigenic in immunocompromised mice. On the basis of previous observations that glioblastoma cells cultured with serum lose the EGFR amplification rapidly and that EGF can inhibit the growth of EGFR-amplified tumor cells, we hypothesized that serum-free and EGF-free culture conditions could promote maintenance of the EGFR amplification. EXPERIMENTAL DESIGN: Cells from EGFR-amplified glioblastomas were taken into culture using neural stem cell conditions with modifications, including varying oxygen concentrations and omission of routine EGF supplementation. RESULTS: High-level EGFR amplification was rapidly lost in 5 glioblastoma cultures supplemented with EGF, whereas it was preserved in cultures from the same tumors established without EGF. Cultures from 2 glioblastomas developed into pairs of cell lines, with either stable maintenance or irreversible loss of high-level EGFR amplification in the majority of cells. One EGFR-amplified cell line preserved expression of the receptor variant EGFRvIII. Cell lines with high-level EGFR amplification/EGFRvIII expression formed highly aggressive tumors in nude mice, whereas nonamplified cell lines were either nontumorigenic or grew significantly more slowly. In contrast, nonamplified cell lines proliferated faster in vitro. All cell lines responded to erlotinib, with inhibition of receptor activation and proliferation but partly different effects on downstream signaling and migration. CONCLUSIONS: Isogenic glioblastoma cell lines maintaining stable differences in EGFR/EGFRvIII status can be derived by varying exposure to EGF ligand and reflect the intratumoral genetic heterogeneity. PMID- 22316603 TI - Phase I/II trial of carboplatin and paclitaxel chemotherapy in combination with intravenous oncolytic reovirus in patients with advanced malignancies. AB - PURPOSE: Reovirus type 3 Dearing (RT3D) replicates preferentially in Ras activated cancers. RT3D shows synergistic in vitro cytotoxicity in combination with platins and taxanes. The purpose of this phase I/II study was to assess RT3D combined with carboplatin/paclitaxel in patients with advanced cancers. EXPERIMENTAL DESIGN: Patients were initially treated in a dose-escalating, phase I trial with intravenous RT3D days 1 to 5, carboplatin [area under curve (AUC) 5, day 1] and paclitaxel (175 mg/m(2), day 1) 3-weekly. RT3D was escalated through three dose levels: 3 * 10(9), 1 * 10(10), and 3 * 10(10) TCID(50) in cohorts of three. Primary endpoints were to define the maximum tolerated dose and dose limiting toxicity and to recommend a dose for phase II studies. Secondary endpoints included pharmacokinetics, immune response, and antitumor activity. A subsequent phase II study using the 3 * 10(10) TCID(50) dose characterized the response rate in patients with head and neck cancer. RESULTS: Thirty-one heavily pretreated patients received study therapy. There were no dose-limiting toxicities during dose-escalation and most toxicities were grade I/II. Overall effectiveness rates were as follows: one patient had a complete response (3.8%), six patients (23.1%) had partial response, two patients (7.6%) had major clinical responses clinically evaluated in radiation pretreated lesions which are not evaluable by Response Evaluation Criteria in Solid Tumors (RECIST), nine patients (34.6%) had stable disease, and eight patients (30.8%) had disease progression. Viral shedding was minimal and antiviral immune responses were attenuated compared with previous single-agent data for RT3D. CONCLUSIONS: The combination of RT3D plus carboplatin/paclitaxel is well tolerated with evidence of activity in cancer of the head and neck. A randomized phase III study is currently open for recruitment. PMID- 22316605 TI - Isoflurane anesthesia precipitates tauopathy and upper airways dysfunction in pre symptomatic Tau.P301L mice: possible implication for neurodegenerative diseases. AB - The postoperative cognitive decline resulting from volatile anesthesia is gaining acceptance as a major health problem. The common anesthetic isoflurane is suspected to precipitate neurodegeneration in Alzheimer's disease by unknown mechanisms. We previously validated that 8month old Tau.P301L mice suffer upper airways defects related to tauopathy within the Kolliker-Fuse nucleus that controls upper airways function. We now report that isoflurane anesthesia in young, pre-symptomatic Tau.P301L mice triggered precocious upper airways defects and tauopathy in several brainstem nuclei, including the nucleus ambiguus that contains upper airways motor neurons and the Kolliker-Fuse. The prescription drug memantine, identified as an NMDA receptor antagonist, prevented the post anesthesia upper airways dysfunction and alleviated tauopathy in the nucleus ambiguus and Kolliker-Fuse. We further identified protocols of anesthesia in young Tau.P301L mice that mitigated adverse effects of isoflurane anesthesia. Thus, our experimental findings in a validated mouse model for tauopathy demonstrate the link between isoflurane anesthesia, earlier onset of tauopathy and earlier onset of functional deficits, highlight the implication of NMDA receptors in the mechanisms mediating the adverse effects of isoflurane, and potentially identify safer protocols for anesthesia in patients with tauopathy. PMID- 22316606 TI - A solid-state NMR study of C(70): a model molecule for amorphous carbons. AB - We show that natural abundance, solid-state MAS-NMR (13)C INADEQUATE spectra can be recorded for crystallized C(70), using the through-bond J-coupling for the magnetization transfer. The effect of strong J-coupling can be lessened at high magnetic fields, allowing the observation of cross-peaks between close resonances. DFT calculations of the chemical shifts show an excellent agreement with the experimental values. A correlation is observed between the average CCC bond angles and the (13)C chemical shift, offering a way to understand the dispersion of (13)C chemical shifts in nanoporous activated carbons in terms of local deviations from planarity. PMID- 22316607 TI - Can the crystallization rate be independent from the crystallization enthalpy? The case of amorphous silicon. AB - The crystallization enthalpy measured in a large series of amorphous silicon (a Si) materials varies within a factor of 2 from sample to sample (Kail et al 2011 Phys. Status Solidi RRL 5 361). According to the classical theory of nucleation, this variation should produce large differences in the crystallization kinetics leading to crystallization temperatures and activation energies exceeding 550 degrees C and 1.7 eV, respectively, the 'standard' values measured for a-Si obtained by self-implantation. In contrast, the observed crystallization kinetics is very similar for all the samples studied and has no correlation with the crystallization enthalpy. This discrepancy has led us to propose that crystallization in a-Si begins in microscopic domains that are almost identical in all samples, independently of their crystallization enthalpy. Probably the existence of microscopic inhomogeneities also plays a crucial role in the crystallization kinetics of other amorphous materials and glasses. PMID- 22316608 TI - Subacute encephalopathy associated with aquaporin-4 autoantibodies: a report of 2 adult cases. PMID- 22316609 TI - Diffusion tensor imaging as a surrogate marker for outcome after perimesencephalic subarachnoid hemorrhage. PMID- 22316610 TI - Percutaneous discectomy: minimally invasive method for treatment of recurrent lumbar disc herniation. AB - OBJECTIVES: Recurrent lumbar disc herniation has been reported in 5-11% of patients. Revision surgery carries a higher risk of complications due to epidural scar formation and difficulty in identifying the bony landmarks. The present study was conducted to apply an innovative procedure which optimally has lower complications, and decrease the need for major surgery for high risk patients. PATIENT AND METHOD: Our study presents six patients of recurrent herniation after past performed procedures such as microdiscectomy, or a laminectomy and discectomy who were readmitted and treated with APLD (automated percutaneous lumbar discectomy) as the first line. The APLD criteria for patient selection in the present study are those with predominantly leg pain that failed conservative treatment for at least 6 weeks and, after lumbar surgery for at least 6 months at the same level. RESULTS: Four of the patients have sciatica recovery signs ranging between excellent to good and, two showed no improvement. None of the screened patients in this study developed any serious complications. CONCLUSION: Although this is a small series with a short follow up duration, it can be postulated that in the absence of objective evidence of spinal instability, recurrent disc herniation with predominantly leg pain may be treated by APLD as a first line. This can be especially helpful in patients with high risk for anesthesia. PMID- 22316611 TI - Subacute combined degeneration of the spinal cord in a vegan. PMID- 22316612 TI - Systems neurobiology of restorative neurology and future directions for repair of the damaged motor systems. AB - Restoring movement control after central nervous system injury requires reconnecting the brain and spinal motoneurons, and doing so with sufficient precision and strength to enable robust voluntary muscle recruitment. Whereas the connection between the upper motoneuron in motor cortex and alpha-motoneurons was thought to be the only important connection for normal motor function in humans, we know that a multiplicity of motor circuits are recruited during normal motor control. Multiplicity of functionally important motor circuits points to the myriad possibilities of intervention that restorative neurology can turn to for repairing motor systems connections to recover movement control after injury. New motor systems repair strategies in animal models and humans are tapping into distributed motor control functions of the spinal cord; neural activity-based approaches, especially for corticospinal tract repair; and circuit-selective activation approaches. I focus on studies harnessing activity-based therapeutic approaches to promote sprouting of spared corticospinal tract axons after injury and redirecting potentially maladaptive plasticity. I discuss that we can see on the near horizon, many different strategies for repairing motor systems connections after injury. PMID- 22316613 TI - Characterisation and improvement of a reference cylindrical sonoreactor. AB - This paper describes theoretical and experimental methods for characterising the performance of a 25 kHz sonochemical reactor (RV-25), which is being developed as a reference facility for studying acoustic cavitation at the National Physical Laboratory (NPL). Field measurements, acquired in different locations inside the sonoreactor, are compared with finite element models at different temperatures, showing that relatively small temperature variations can result in significant changes in the acoustic pressure distribution (and consequent cavitation activity). To improve stability, a deeper insight into the way energy is transferred from the power supply to the acoustic field is presented, leading to criteria - based on modal analysis - to dimension and verify an effective temperature control loop. The simultaneous use of measurements and modelling in this work produced guidelines for the design of multi-frequency cylindrical sonoreactors, also described. PMID- 22316614 TI - Pretargeting vs. direct targeting of human betalox5 islet cells subcutaneously implanted in mice using an anti-human islet cell antibody. AB - INTRODUCTION: We previously demonstrated MORF/cMORF pretargeting of human islets and betalox 5 cells (a human beta cell line) transplanted subcutaneously in mice with the anti-human islet antibody, HPi1. We now compare pretargeting with direct targeting in the beta cell transplant model to evaluate the degree to which target/non-target (T/NT) ratios may be improved by pretargeting. METHODS: Specific binding of an anti-human islet antibody HPi1 to the beta cells transplanted subcutaneously in mice was examined against a negative control antibody. We then compared pretargeting by MORF-HPi1 plus 111In-labeled cMORF to direct targeting by 111In-labeled HPi1. RESULTS: HPi1 binding to betalox5 human cells in the transplant was shown by immunofluorescence. Normal organ 111In backgrounds by pretargeting were always lower, although target accumulations were similar. More importantly, the transplant to pancreas and liver ratios was, respectively, 26 and 10 by pretargeting as compared to 9 and 0.6 by direct targeting. CONCLUSIONS: Pretargeting greatly improves the T/NT ratios, and based on the estimated endocrine to exocrine ratio within a pancreas, pretargeting may be approaching the sensitivity required for successful imaging of human islets within this organ. PMID- 22316616 TI - Response and sensitivity of lipid related molecular structure to wet and dry heating in canola tissue. AB - Heat treatments are used to manipulate nutrient utilization, availability and functional properties. The objective of this study was to characterize any molecular level changes of the functional groups associated with lipid structure in canola (Brassica) seed, as affected during the wet and dry heat treatment processes using molecular spectroscopy. The parameters included lipid CH(3) asymmetric (ca. 2970-2946 cm(-1)), CH(2) asymmetric (ca. 2945-2880 cm(-1)), CH(3) symmetric (ca. 2881-2864 cm(-1)) and CH(2) symmetric (ca. 2864-2770 cm(-1)) functional groups, lipid carbonyl CO ester group (ca. 1774-1711 cm(-1)), lipid unsaturation group (CH attached to C-C) (ca. 3007 cm(-1)) as well as their ratios. Hierarchical cluster analysis (CLA) and principal components analysis (PCA) were conducted to identify molecular spectral differences. Raw canola seeds were used for the control or autoclaved at 120 degrees C for 1h (HT-1: wet heating) or dry roasted at 120 degrees C for 1h (HT-2: dry heating). Molecular spectral analysis of lipid functional group ratios were not significantly changed (P>0.05) in the CH(2) asymmetric to CH(3) asymmetric stretching band peak intensity ratios for canola seed. Both wet (HT-1) and dry heating method (HT-2) had no significant effect (P>0.05) on lipid carbonyl CO ester group and lipid unsaturation group (CH attached to CC). Multivariate molecular spectral analyses, CLA and PCA, were unable to make distinctions between the different treatment original spectra at the CH(3) and CH(2) asymmetric and symmetric region (ca. 2992 2770 cm(-1)), unsaturated lipids band region (ca. 3025-2993 cm(-1)) and lipid carbonyl CO ester band region (ca. 1774-1711 cm(-1)). The results indicated that both dry and wet heating of given intense had no impact to the molecular spectrum in lipid related functional groups of canola seed, and was not strong enough to elicit heat-induced changes in lipid conformation. PMID- 22316617 TI - Development of a fluorescent chelating ligand for scandium ion having a Schiff base moiety. AB - A fluorescent ligand, 1-(2-hydroxy-3-methoxybenzaldehyde)-4-aminosalicylhydrazone (HMB-ASH), was newly designed and synthesized, and its fluorescence characteristics for metal ions were investigated in the pH range 3.0-10.5 (at a difference of 0.5 for each metal). After testing 31 different metal ions, it was found that HMB-ASH was able to emit fluorescence intensely at 512 nm with an excitation wavelength of 353 nm in the presence of Sc(3+), one of the rare earth metals, at pH values around 3.5 and 8.0. The other metal ions hardly showed fluorescence with HMB-ASH. The fluorescence was more intense at pH 8.0, and the detection limit of Sc(3+) in a buffer solution (pH 8.0) was approximately 18.8 nmol L(-1) (0.85 ppb). PMID- 22316618 TI - Iodine or Not (IoN) for low-risk differentiated thyroid cancer: the next UK National Cancer Research Network randomised trial following HiLo. PMID- 22316619 TI - Reactive oxygen species and nitric oxide effect on the steroid hormone binding with serum albumin. AB - The interaction of a series of steroid hormones (DHEA, progesterone, testosterone, estradiol) with serum albumin immobilized on porous silica particles and the effect of reactive oxygen species and nitric oxide on this interaction were studied using a biochromatographic approach. The determination of enthalpy and entropy changes of this binding indicated that van der Waals interactions and hydrogen bonds predominated the hormone association with albumin. Reactive oxygen species (H(2)O(2) and OH*) increased the hormone binding affinity to albumin. On the other hand, this binding was decreased with the presence of NO*. This variation was due to conformational changes in the binding region explained by the oxidation of some residues such as free thiol and arginine. The thermodynamic analysis showed that free radical affects the van der Waals forces and/or a hydrogen bond of the hormone binding with albumin. These results explained the role of reactive oxygen species and nitric oxide in the hormone free fraction level in the blood. PMID- 22316620 TI - Application of quality by design elements for the development and optimization of an analytical method for protamine sulfate. AB - The purpose of this study was to develop a robust reverse phase-HPLC method for the separation of hydrolyzed protamine sulfate peptides using a quality by design approach. A Plackett-Burman experimental design was utilized to screen the effects of mobile phase pH, flow rate, column temperature, injection volume and methanol concentration on peak resolution and USP tailing. Multivariate regression and Pareto ranking analyses showed that mobile phase pH, column temperature and injection volume were statistically significant (p<0.05) factors affecting the resolution and tailing of the peaks. A Box-Behnken experimental design with response surface methodology was then utilized to evaluate the main, interaction, and quadratic effects of these three factors on the selected responses. A desirability function applied to the optimized conditions predicted peak resolutions between 1.99 and 3.61 and tailing factor between 1.02 and 1.45 for the four peptide peaks of protamine sulfate with the following chromatographic conditions; an isocratic mobile phase consisting of 100mM monosodium phosphate buffer pH 2.25, 1.8% acetonitrile and 0.3% methanol. The injection volume was 20 MUl, with a column temperature of 24 degrees C and a flow rate of 1.0 ml/min and a total run time of less than 25 min. The optimized chromatographic method was validated according to ICH Q2R1 guidelines and applied to separate and compare the peaks of protamine sulfate from five different sources. Analyses of the peptide peaks of the five protamine sulfate samples showed no significant differences in their compositions. The results clearly showed that quality by design concept could be effectively applied to optimize an HPLC chromatographic method for protein analysis with the least number of experimental runs possible. PMID- 22316621 TI - Micelle to solvent stacking of tricyclic psychiatric drugs in capillary electrophoresis. AB - A capillary electrophoresis (CE) method with UV-detection based on preconcentration with on-line micelle to solvent stacking (MSS) was optimized and validated to the simultaneous determination of tricyclic psychiatric drugs in urine samples. Sample preparation was based on liquid-liquid extraction (LLE) of analyzed drugs from biological samples. The electrophoretic conditions were: separation buffer composed of 40 mM sodium dihydrogen phosphate (pH 3.7) and 60% methanol (v/v), uncoated fused silica capillary (75 MUm i.d.* 57 cm length), UV spectrophotometric detection at 254 nm, injection time 90 s at 3.45 kPa, applied voltage 25 kV, and temperature 22 degrees C. The advantage of proposed MSS strategy is its improved limit of detection of analytes compared to traditional CE technique. This is important for the analysis of drugs presented at very low concentration in biological samples. The developed CE method allows determination of psychotropic drugs at ng/ml level in human urine. This is the first report, presenting the possibility of determination of these drugs in urine samples by MSS-CE. PMID- 22316622 TI - The use of total reflectance X-ray fluorescence (TXRF) for the determination of metals in the pharmaceutical industry. AB - The control of residual metals in active pharmaceutical ingredients (API's) and intermediates is critical because of their potential toxic effects. A variety of technologies are available to measure residual metals in pharmaceutical compounds including, AAS, ICP-AES, and ICP-MS. The newest technology is total reflectance X ray fluorescence spectroscopy (TXRF) which uses primary X-rays to excite atoms which then emit secondary X-rays. The emitted X-rays are characteristic of the individual elements present, and the intensities of the emitted X-rays are proportional to the concentrations of the elements present in the sample. The benefits of TXRF are that it is essentially unaffected by matrix effects, is very sensitive (ppb's), requires small amounts of sample (5-10 mg), and requires very little sample preparation time. During this study, TXRF was used to quantitatively measure residual metals in API's and intermediates and such topics as sample preparation, sensitivity, linearity, reproducibility and accuracy are discussed. The results obtained by TXRF were compared with those obtained by ICP MS for the same samples for Pd and Cu measurement, and statistical analysis indicated that the results obtained by the two technologies are equivalent at the 95% confidence level. A comparison is also made of the capabilities of the instruments using a tungsten (W) or a molybdenum (Mo) source for excitation. Both instruments could be used for the quantitative determination of residual metals in pharmaceuticals. PMID- 22316623 TI - Scorpion bite prevalence and complications: report from a referral centre in southern Iran. AB - In this study we describe the clinical features of scorpion bites in southern Iran. The records of scorpion bite victims from January 2000 to January 2009 were obtained from the record library of the Shiraz Nemazi Hospital, Shiraz, Iran. A total of 232 scorpion bite patients were included. Only 14 patients (6%) developed systemic complications. Acute renal failure (ARF) and disseminated intravascular coagulation (DIC) were the most prevalent systemic complications. The renal toxicity of scorpion envenomation is mostly due to Hemiscorpius lepturus stings and this complication is more common in younger children. This may be due to a higher ratio of venom to body mass compared with adults. H. lepturus venom is naturally cytotoxic and may bind directly to kidney tissue causing tubular injury and inducing DIC and haemolysis. PMID- 22316624 TI - Renal cortical necrosis, peripheral gangrene, perinephric and retroperitoneal haematoma in a patient with a viper bite. AB - Snakebites are estimated to affect more than 2.5 million people annually, of whom more than 100,000 die. Viper bites cause various systemic symptoms such as: coagulopathy; haemolysis; acute renal failure; a generalized increase in capillary permeability; rhabdomyolysis; and neurotoxicity. Wide spectrums of vascular complications are seen. We report the case of a patient developing gangrenous changes in a lower limb along with the development of perinepheric and retroperitoneal haematoma with acute cortical necrosis of the kidneys. PMID- 22316625 TI - Plasma follistatin-like protein 1 is elevated in Kawasaki disease and may predict coronary artery aneurysm formation. AB - OBJECTIVE: To determine whether plasma levels of follistatin-like protein 1 (FSTL 1), a pro-inflammatory protein produced by mesenchymal tissue, including cardiac myocytes, correlate with the development of Kawasaki disease (KD) and coronary artery aneurysms (CAA). STUDY DESIGN: FSTL-1 plasma levels were measured serially with enzyme-linked immunosorbent assay in 48 patients with KD at time of diagnosis and, when available, 2 weeks, 6 weeks, and 6 months after onset of disease. These were compared with FSTL-1 plasma levels in 23 control subjects. Data were analyzed with generalized estimating equations. RESULTS: Plasma FSTL-1 levels were elevated in patients with acute KD compared with control subjects (P = .0086). FSTL-1 levels remained significantly elevated at 2 weeks after disease onset, but returned to control levels by 6 months. Seven patients with CAA had significantly higher FSTL-1 levels at the time of diagnosis than patients in whom aneurysms did not develop (P = .0018). Sensitivity and specificity rates for CAA at a specific FSTL-1 cutoff point (178 ng/mL) were 85% and 71%. CONCLUSIONS: Plasma levels of FSTL-1 are elevated in acute KD and may predict cardiac morbidity in this disease. These results suggest a possible role for FSTL-1 in the formation of CAAs. PMID- 22316626 TI - Parvovirus B19 and necrotizing enterocolitis in neonates. PMID- 22316627 TI - Resistance patterns with tyrosine kinase inhibitors in melanoma: new insights. AB - PURPOSE OF REVIEW: After years of therapeutic approaches with limited effects in metastatic melanoma, new inhibitors of serine-threonine and tyrosine kinases have demonstrated impressive clinical efficacy and improved survival. RECENT FINDINGS: This review explains the molecular background for the development of specific kinase inhibitors and briefly summarizes their clinical impact on advanced melanoma. SUMMARY: Despite robust early clinical efficacy, the antiproliferative effect of these kinase inhibitors is limited. The resistance mechanisms are explored currently and will help to identify new targets for melanoma therapy. PMID- 22316628 TI - Spectroscopic, structural and thermodynamic properties of chlorpyrifos bound to serum albumin: A comparative study between BSA and HSA. AB - Chlorpyrifos (CPF) is a widely used organophosphate insecticide which could bind with human serum albumin (HSA) and bovine serum albumin (BSA). The binding behavior was studied employing fluorescence, three-dimensional fluorescence, Circular dichroism (CD) spectroscopy, UV-vis absorption spectroscopy, electrochemistry and molecular modeling methods. The fluorescence spectra revealed that CPF causes the quenching of the fluorescence emission of serum albumin. Stern-Volmer plots were made and quenching constants were thus obtained. The results suggested the formation of the complexes of CPF with serum albumins, which were in good agreement with the results from electrochemical experiments. Association constants at 25 degrees C were 3.039 * 10(5) mol L(-1) for HSA, and 0.3307 * 10(5) mol L(-1) for BSA, which could affect the distribution, metabolism, and excretion of pesticide. The alterations of protein secondary structure in the presence of CPF were confirmed by the evidences from UV and CD spectra. Site competitive experiments also suggested that the primary binding site for CPF on serum albumin is close to tryptophan residues 214 of HSA and 212 of BSA, which was further confirmed by molecular modeling. PMID- 22316629 TI - Baseline haptoglobin concentrations are repeatable and predictive of certain aspects of a subsequent experimentally-induced inflammatory response. AB - Ecologists sometimes assume immunological indices reflect fundamental attributes of individuals-an important assumption if an index is to be interpreted in an evolutionary context since among-individual variation drives natural selection. Yet the extent to which individuals vary over different timescales is poorly understood. Haptoglobin, an acute phase protein, is an interesting parameter for studying variability as it is easily quantified and concentrations vary widely due to the molecule's role in inflammation, infection and trauma. We quantified haptoglobin in pigeon plasma samples collected over fourteen months and calculated repeatability to evaluate if haptoglobin concentration is a distinctive trait of individuals. We also explored the capacity of baseline haptoglobin concentrations to predict an array of physiological changes associated with a subsequent experimentally-induced inflammatory response. Maximum repeatability, which occurred over a short mid-winter interval, equaled 0.57. Baseline haptoglobin concentrations predicted response haptoglobin concentrations better than any other endotoxin-induced change. Overall, we identified several strengths and limitations of baseline [Hp] quantification. Acknowledging these qualities should lead to more refined conclusions in studies of the ecology and evolution of immune function. PMID- 22316630 TI - Nurses' knowledge of pressure ulcer prevention in ogun state, Nigeria: results of a pilot survey . AB - Pressure ulcer (PU) development remains a significant complication among at-risk patients. Optimal prevention strategies start with knowledge about current evidence-based prevention interventions. A pilot study was conducted to describe nurses' level of knowledge of PU preventive interventions and to test the reliability of the Pressure Ulcer Knowledge Test (PUKT) among Nigerian nurses. One hundred, eleven (111) nurses were purposively selected from specific wards of a state teaching hospital in South West Nigeria. While 106 nurses (95.5%) correctly identified patients at risk for PU development, 78 participants (70.3%) had low (<59% correct) prevention intervention knowledge scores. No significant differences in PU prevention intervention knowledge scores were observed between nurses with different educational backgrounds (P = 0.317) or years of working experience (P >0.005). The Cronbach's alpha coefficient for reliability was 0.861. The results of this study confirm that many PU prevention interventions in Nigeria are based on tradition and that a structured educational approach is needed to enable Nigerian nurses to provide evidence-based PU prevention interventions. PMID- 22316631 TI - The Braden Scale cannot be used alone for assessing pressure ulcer risk in surgical patients: a meta-analysis. AB - The validity and reliability of the Braden Scale for pressure ulcer development has been established in a variety of patient care settings, but studies suggest the scale does not capture risk factors in surgical patients. The purpose of this metaanalysis was to assess the predictive validity of the Braden Scale for pressure ulcer development in surgical patients. A literature search using PubMed and Web of Science databases (through July 2011) was conducted to identify all clinical studies on predicting pressure ulcers in surgical patients using the Braden Scale. To be eligible for inclusion, studies had to include sensitivity (true positive rate, TPR) and specificity (true negative rate, TNR) results or include sufficient data to calculate these factors. Study quality was assessed using the 14-item Quality Assessment of Diagnostic Accuracy Studies (QUADAS) instrument, and two-by-two tables of predictive validity were constructed from each article. Meta-analysis for predictive validity was performed, including calculation of pooled sensitivity, pooled specificity, diagnostic odds ratio (DOR), construction of summary receiver operating characteristic (SROC) curves, and overall diagnostic accuracy (Q*). Three studies (N = 609 patients) met the meta-analysis inclusion criteria. The pooled estimates for sensitivity and specificity were 0.42 (95% CI: 0.38 to 0.47) and 0.84 (95% CI: 0. 83 to 0.85), respectively, yielding a combined DOR of 4.40 (95% CI: 2.98 to 6.50). The area under the ROC curve (AUC) was 0.6921 +/- 0.0346, and the Q* was 0.6466 +/- 0.0274. Significant heterogeneity was noted between the included studies with Q value 34.49 (P = 0.0321), and I2 for pooled sensitivity, pooled specificity, and pooled DOR was 88.7%, 98.6%, and 39.1%, respectively. Although the observed heterogeneity between studies may have affected the results, the low values for overall diagnostic accuracy (Q*) and diagnostic capability (AUC) indicate the Braden Scale has low predictive validity for pressure ulcer risk in surgical patients. A new pressure ulcer risk assessment scale for surgical patients should be developed and tested. PMID- 22316632 TI - The costs and outcomes of treating a deep pressure ulcer in a patient with quadriplegia . AB - The cost of pressure ulcers, especially Stage III and Stage IV ulcers, is substantial. A 27-year-old man with a 6-year history of quadriplegia developed an ischial pressure ulcer. Twelve months of treatment with wet-to-dry dressings were followed by admission to several facilities and 15 months of care with biological dressings and negative pressure wound therapy (NPWT). When admitted to the authors' wound care center, the wound measured 4.5 cm x 3.2 cm with exposed bone. A review of his insurance records showed that paid claims totaled $242,350, including $52,992 for NPWT rental costs. The patient was considered a good candidate for minimally invasive surgical intervention with external tissue expanders. Following a 14-day course of antibiotics to treat his infection, the wound was debrided and the tissue expanders applied. After 16 days, the wound was closed. The patient returned to work 6 weeks after the procedure. At the 23-month follow-up, the wound remained closed. Insurance payments for the care that resulted in wound closure totaled $43,814. This case study illustrates the potential of the external tissue expansion technique to close deep pressure ulcers within a relatively short amount of time at comparatively lower cost. Studies including control treatments are needed to confirm these conclusions. PMID- 22316633 TI - Comparison of dermal absorption of zinc from different sunscreen formulations and differing UV exposure based on stable isotope tracing. AB - In a pilot study to determine if zinc (Zn) from zinc oxide nanoparticles in sunscreen can penetrate human skin in vivo, nanoparticles (~30nm) of a stable isotope (52% (68)Zn enrichment) were incorporated into an essentially phytochemical-based formulation and applied to the backs of 3 human subjects twice daily for 5 days during the Southern Hemisphere winter. Blood and urine were collected prior to application and at regular intervals and up to 50 days. As observed in a larger outdoor trial following this pilot study but with a different formulation and with UV exposure: values of (68)Zn in blood continued to increase beyond the 5 day application phase with the highest measurement at 14 days after the first application; variable amounts of the (68)Zn tracer were observed in urine; and the amounts of extra Zn added to blood were small and indicate very low levels of absorption (minimal estimate <0.01% of the applied dose) through the skin. Reasons for differences in absorption detected in the stable isotope trials and previous investigations include: the sensitivity of the stable isotope method; the duration of the investigations; the number of applications of sunscreen formulation; in vitro methods with excised skin; lack of measurement of blood and urine; no skin flexing; and lack of UV exposure. PMID- 22316634 TI - LabSystem Gen, a tool for structuring and analyzing genetic data in histocompatibility laboratories. AB - Analysis of HLA data involves queries on web portals, whose search parameters are data stored in laboratories' databases. In order to automate these queries, one approach is to structure laboratory data into a database and to develop bioinformatic tools to perform the data mapping. In this context, we developed the LabSystem Gen tool that allows users to create a Laboratory Information System, without programming. Additionally we implemented a framework that provides bioinformatic tools, transparent access to public HLA (human leukocyte antigen) information resources. We demonstrated the LabSystemGen system by implementing BMDdb, which is a LIMS that manages data of recipients and donors of organ transplant. PMID- 22316635 TI - Pardoprunox as adjunct therapy to levodopa in patients with Parkinson's disease experiencing motor fluctuations: results of a double-blind, randomized, placebo controlled, trial. AB - AIMS: To determine the efficacy and safety of pardoprunox in levodopa-treated patients with Parkinson's disease (PD) experiencing motor fluctuations. METHODS: Patients were randomized to pardoprunox (up to 42 mg/day, n = 150) or placebo (n = 144). Pardoprunox was titrated to an optimal dose over 7 weeks, followed by a 12-week stable dose period. The primary efficacy variable was the change from baseline to study endpoint in total daily OFF time, based on patient diaries. Secondary analyses included the change in ON time without troublesome dyskinesias, UPDRS-ADL + Motor ON, UPDRS-ADL OFF and PDQ-39. Subgroup analyses explored the impact of pardoprunox on dyskinesias (UPDRS items 32 + 33), depression (Hospital Anxiety Depression Scale) and pain (Visual Analogue Scale). RESULTS: Pardoprunox significantly reduced OFF time versus placebo (-1.62 h/day versus -0.92 h/day, respectively, p = 0.0215). Compared to placebo, pardoprunox improved ON time without troublesome dyskinesias (p = 0.0386), UPDRS-ADL + Motor ON (p = 0.0003), and UPDRS-ADL OFF (p < 0.0001), while no significant difference was observed on PDQ-39. A high drop-out rate due to adverse events (AEs) (pardoprunox, 37%; placebo, 12%) suggested that the selected dose range may have been too high, and/or titration was too rapid. CONCLUSIONS: Pardoprunox decreased OFF time and increased ON time without troublesome dyskinesias in levodopa treated PD patients. The high drop-out rate at the selected doses justifies the investigation of lower doses. The impact of pardoprunox on dyskinesias and non motor symptoms deserves further investigation. PMID- 22316636 TI - A first-principles study of the effect of charge doping on the 1D polymerization of C(60). AB - We study the interplay between charge doping and intermolecular distance in the polymerization of C(60) fullerene chains by means of density functional theory based first-principles calculations. The potential energy surface analysis shows that both the equilibrium intermolecular distance of the unpolymerized system and the polymerization energy barrier are inversely proportional to the electron doping of the system. We analyze the origin of this charge-induced polymerization effect by studying the behavior of the system's wavefunctions around the Fermi level and the structural modifications of the molecules as a function of two variables: the distance between the centers of the molecules and the number of electrons added to the system. PMID- 22316638 TI - Neurological soft signs and subcortical brain morphology in recent onset schizophrenia. AB - BACKGROUND: Minor motor and sensory deficits or neurological soft signs (NSS) are frequently found in patients with schizophrenia at any stage of their illness. The thalamus and basal ganglia are accepted as being important for both motor control and integration of sensory input. However, whether NSS are related to alterations of these brain regions remains controversial. METHOD: Twenty patients with recent onset schizophrenia were investigated using high-resolution magnetic resonance imaging (MRI) at 3 Tesla. NSS were examined on the Heidelberg Scale after remission of acute symptoms and related to both volumetric and shape measurements of thalamus, caudate nucleus, putamen, and globus pallidus, respectively. Age, education, medication and duration of illness were considered as potential confounders. RESULTS: NSS were associated with structural alterations predominantly in the thalamus, the left caudate nucleus, and in the right globus pallidus. According to shape analyses these associations referred to regionally specific morphometric alterations rather than to global atrophy of the respective structures. CONCLUSION: Our findings provide new insights into the association of NSS with brain morphometric alterations and lend further support to an involvement of multiple subcortical regions in schizophrenia. PMID- 22316639 TI - Psychotropic drug-induced weight gain and other metabolic complications in a Swiss psychiatric population. AB - PURPOSE: To describe the weight gain-related side-effects of psychotropic drugs and their consequences on metabolic complications (hypercholesterolemia, obesity) in a Swiss cohort of psychiatric patients. METHOD: This cross-sectional observational study was performed in an out-patient psychiatric division with patients having received for more than 3 months the following drugs: clozapine, olanzapine, quetiapine, risperidone, lithium, and/or valproate. Clinical measures and lifestyle information (smoking behaviour, physical activity) were recorded. RESULTS: 196 inclusions were completed. Weight gain (>=10% of initial weight) following drug treatment was reported in 47% of these patients. Prevalence of obesity (BMI >= 30), hypercholesterolemia (>=6.2 mmol/L) and low HDL-cholesterol (<1.0 mmol/L in men, <1.3 mmol/L in women) were present in 38%, 21%, and 27% of patients, respectively. A higher standardised dose, an increase of appetite following medication introduction, the type of medication (clozapine or olanzapine > quetiapine or risperidone > lithium or valproate), and the gender were shown to be significantly associated with evolution of BMI. CONCLUSION: High prevalence of obesity and hypercholesterolemia was found in an out-patient psychiatric population and confirms drug-induced weight gain complications during long-term treatment. The results support the recently published recommendations of monitoring of metabolic side-effects during treatment with atypical antipsychotics. Moreover, the weight gain predictors found in the present study could help to highlight patients with special health care management requirement. PMID- 22316640 TI - Pre-schoolers suffering from psychiatric disorders show increased cortisol secretion and poor sleep compared to healthy controls. AB - BACKGROUND: Various studies of child cortisol secretion and sleep show a close association between poor sleep, deterioration of the HPA axis and unfavorable psychological functioning. However, there is little evidence as to whether these associations are clearly present in pre-school children suffering from psychiatric disorders. METHOD: A total of 30 pre-schoolers suffering from psychiatric disorders (anxiety, adjustment disorders, emotional and attachment disorder; hyperactivity or oppositional disorder) and 35 healthy controls took part in the study. Saliva cortisol secretion was assessed both at baseline and under challenge conditions. Sleep was assessed via activity monitoring for seven consecutive days and nights, using a digital movement-measuring instrument. Parents and teachers completed questionnaires assessing children's cognitive, emotional and social functioning. The Berkeley Puppet Interview provided child based reports of cognitive-emotional processes. RESULTS: Compared to healthy controls, children suffering from psychiatric disorders had much higher cortisol secretion both at baseline and under challenge conditions. Sleep was also more disturbed, and parents and teachers rated children suffering from psychiatric disorders as cognitively, emotionally and behaviorally more impaired, relative to healthy controls. Children with psychiatric disorders reported being more bullied and victimized. CONCLUSIONS: In five-year old children the presence of psychiatric disorders is reflected not only at psychological, social and behavioral, but also at neuroendocrine and sleep-related levels. It is likely that these children remain at increased risk for suffering from psychiatric difficulties later in life. PMID- 22316641 TI - Diabetes-specific quality of life after a low-carbohydrate and low-fat dietary intervention. AB - PURPOSE: The purpose of the study was to examine the impact of a 12-month weight loss intervention with either a low-carbohydrate or a low-fat diet on quality of life (QOL) among obese patients with type 2 diabetes. METHODS: Participants were enrolled in a randomized trial comparing a low-carbohydrate to a low-fat diet in type 2 diabetes. QOL was assessed with the Diabetes-39 questionnaire, which measures QOL within 5 distinct scales: anxiety and worry, diabetes control, energy and mobility, social burden, and sexual functioning. Repeated measures ANOVA compared change in QOL scales at baseline and 6 and 12 months. RESULTS: Forty-six participants completed all measures. Following 12 months, there was a significant reduction in the scores related to sexual function and energy and mobility, suggesting improvement in QOL related to these domains. These changes were not significantly different between dietary arms. Changes in weight, A1C, and dietary composition were not significantly correlated with changes in QOL. CONCLUSIONS: Participants with diabetes have various options for weight loss. Dietary interventions with either low-carbohydrate or low-fat diets may lead to some improvements in QOL in patients with type 2 diabetes. PMID- 22316642 TI - Use of the Mastery of Stress Instrument in caregivers of children newly diagnosed with type 1 diabetes: identifying a need for further intervention. AB - PURPOSE: The purpose of this study was to determine if the Mastery of Stress Instrument (MSI) can assess further education needs of primary caregivers of children newly diagnosed with type 1 diabetes. The MSI has been utilized to measure mastery in response to both illness and interventions, including education. The primary objective was to correlate MSI subscales and stress scores with caregiver age, ethnicity, gender, and education. Secondary objectives were to correlate MSI scores with child age at diagnosis, payer source, hemoglobin A1C (A1C), emergency room (ER) visits, or hospitalization for diabetic ketoacidosis (DKA). METHODS: Caregivers from a pediatric endocrinology practice completed the MSI after basic diabetes education. Demographic data from caregivers and patients were obtained. A1C, ER, and DKA were evaluated 2 years following completion of the MSI. Descriptive univariate statistics and proportions on nominal or discrete data were used to describe the data. Bivariable analyses included t tests and ANOVAs. RESULTS: Eighty-five of 88 participants completed the instrument. Caregivers between 40 and 49 years of age scored worse on change, acceptance, and growth subscales compared to those 18 to 29 years of age. Those 40 to 49 years of age reported having more stress compared to caregivers 18 to 29 years of age. Males reported having less stress and were more willing to implement change compared to females. No statistically significant relationships between secondary outcomes measurements and MSI scores were detected. CONCLUSIONS: The mastery of stress instrument identified groups of caregivers in need of further education or team interventions. PMID- 22316643 TI - Assessing barriers to medication adherence in underserved patients with diabetes in Texas. AB - PURPOSE: The purpose of this study was to assess (1) medication adherence in individuals with diabetes, (2) barriers to adherence, and (3) what factors were related to medication nonadherence. METHODS: A self-administered anonymous survey was provided to adults with diabetes (N = 59) who used a grocery store chain pharmacy or a community clinic for the underserved. Participants were recruited by pharmacy staff to complete a 10- to 15-minute survey to assess adherence, access, barriers, medication use, and demographics. Adherence was measured using the 8-item Morisky Medication Adherence Scale (MMAS), which is a reliable and valid self-report adherence instrument. Access (e.g., use medications from Mexico, transportation), barriers (e.g., cost, language difficulties), medication use (e.g., complementary and alternative medicine, prescription medication), and demographics were also measured. The survey was available in English and Spanish. Data collection occurred from December 2010 through February 2011. RESULTS: Fifty nine participants completed the survey. Approximately 57% of study participants were male, 85% were Hispanic, and the mean age was 50.4 +/- 10.3 years. Over 50% of participants had hypertension or dyslipidemia and were taking 3 or more medications. Participants (52.6%) reported their health status as good or excellent and over one-half (56%) of the participants were nonadherent (score 0 6). The following factors were significantly (P < .05) related to nonadherence: cost, no refills, poor health status, fewer disease states, and any reason. CONCLUSIONS: This study increased awareness of barriers to medication adherence in a predominantly Hispanic underserved patient population. This may lead to more informed recommendations and perhaps address gaps in health disparities. PMID- 22316644 TI - Effect of perceived control on quality of life in indigent adults with type 2 diabetes. AB - PURPOSE: To examine the relationship between perceived control of diabetes and physical and mental health components of quality of life in indigent adults with diabetes. METHODS: The primary variables, perceived control of diabetes and quality of life, were evaluated among188 patients from a low-income clinic located at an academic medical center. Over a 12-month period, consenting subjects completed the surveys to assess perceived control of diabetes and health related quality of life. Sociodemographic factors (age, gender, race/ethnicity, income, education, employment, marital status, and insurance status) were collected as well as clinical factors like comorbid conditions and use of insulin therapy. Multiple linear regression models were used to assess the independent association of perceived control on quality of life. RESULTS: The sample largely comprised middle-aged women with diabetes, a majority being black; nearly two thirds had at least a high school education and almost three-quarters were unemployed. Mean quality of life scores were generally below national population means. Correlation results indicated a positive relationship between perceived control and both physical and mental quality of life. Regression results supported the positive association between perceived control and quality of life, even when controlling for sociodemographics and comorbidity in the final model. CONCLUSION: Increasing perceived control, perhaps by a combination of education and skills building (ie, self-efficacy), will result in higher perceived quality of life (QOL) among disadvantaged populations with diabetes. PMID- 22316645 TI - Barriers and enablers to introducing comprehensive patient blood management in the hospital. AB - Patient Blood Management (PBM) is a patient-focused multidisciplinary and comprehensive concept that is designed to ensure the optimal, appropriate and safe use of blood and blood products, resulting in better outcome and safety for the recipients. The World Health Organization, in May 2010, adopted a resolution in favour of PBM, on the availability, safety and quality of blood products and their safe and rational use. However, several factors may enhance or hamper this process including health care personnel, available techniques and technologies, devices, standards, guidelines and documentation, quality systems as well as coordination, monitoring and evaluation. The implications in developing countries may have other peculiarities. PMID- 22316648 TI - Impact of corneal cross-linking on drug penetration in an ex vivo porcine eye model. AB - PURPOSE: To analyze the influence of corneal cross-linking (CXL) using ultraviolet-A and riboflavin on corneal drug penetration of topically applied drugs. METHODS: In an ex vivo porcine eye model, eyes were randomly assigned to CXL or control treatment. Central corneal thickness and anterior chamber depth were measured with a Pentacam device. In the CXL group, eyes were treated with CXL using ultraviolet-A (370 nm) and riboflavin, whereas in the control group only riboflavin was applied without irradiation. Subsequently, 0.3% ofloxacin (n = 40 eyes) or 1% voriconazole (n = 40 eyes) eye drops were applied to the cornea every 5 minutes for 30 minutes. Aqueous humour samples were obtained performing an anterior chamber tap. The concentrations of ofloxacin and voriconazole were determined with high-pressure liquid chromatography. Groups were compared performing a Mann-Whitney test. RESULTS: In the CXL group, the mean concentration of ofloxacin (13.33 +/- 4.67 MUg/mL) and voriconazole (52.70 +/- 8.76 MUg/mL) was significantly lower than in the untreated control group (ofloxacin: 18.51 +/- 6.08 MUg/mL, P = 0.005; voriconazole: 62.43 +/- 13.5 MUg/mL, P = 0.01). This corresponds to a reduction in permeability of 27.98% for ofloxacin and 15.59% for voriconazole. Central corneal thickness and anterior chamber depth were comparable in the CXL and control groups (P > 0.05, each). CONCLUSIONS: CXL reduces the corneal permeability of ofloxacin and voriconazole. This may be of clinical significance, for example, in keratitis treatment. PMID- 22316649 TI - Complications of cosmetic wide conjunctivectomy combined with postsurgical mitomycin C application. AB - PURPOSE: To raise awareness among clinicians about the risk of severe complications after cosmetic conjunctivectomy plus postsurgical topical mitomycin C (MMC) treatment. METHODS: We retrospectively reviewed the medical records of 48 consecutive patients who received cosmetic wide conjunctivectomy plus postsurgical topical MMC treatment to eliminate conjunctival injection and visited our outpatient clinic between January 2009 and January 2011. RESULTS: Forty-four patients (91.67%) developed complications after cosmetic wide conjunctivectomy plus postsurgical topical MMC treatment. Complications included chronic conjunctival epithelial defects (22 patients), scleral thinning with (19 patients) or without (2 patients) calcified plaques, fibrovascular conjunctival adhesion at the muscle insertion site (15 patients), chronic dysfunctional tear syndrome (11 patients), avascular zones (10 patients), abnormal vessel growth (5 patients), lymphangiectasis (3 patients), adhesions of Tenon capsule and the conjunctiva at the extraocular muscle insertion site (1 patient), extraocular muscle fiber exposure (1 patient), and diplopia (9 patients). The mean time between surgery and the onset of diplopia was 1.67 months (range, 1-3 months), and the mean deviation was 11.0 prism diopters (range, 0-25 prism diopters) in the primary position. Three patients underwent strabismus surgery due to incomitant esotropia. Eight patients underwent calcified plaque removal because of severe progression of the calcification. Five patients underwent conjunctival flap operation because of severe progressive scleral thinning. CONCLUSIONS: Cosmetic wide conjunctivectomy, which has been advertised as a simple and effective surgical option for the treatment of conjunctival injection, has caused disruption in the normal physiology of the ocular surface, which leads to various devastating complications. PMID- 22316650 TI - Correlation of corneal elevation with severity of keratoconus by means of anterior and posterior topographic analysis. AB - PURPOSE: To investigate the severity of keratoconus in terms of corneal elevation differences with 2 different reference surfaces using topographic analysis. METHODS: Eighty-six eyes of 50 patients with keratoconus of various clinical stages (61 male and 25 female eyes) with mean age of 37.3 +/- 11.6 years were evaluated. Anterior and posterior corneal elevations were measured using topographic analysis (using a rotating Scheimpflug camera), and the imaging data were analyzed to estimate elevation differences as differential values from conventional best-fit-sphere and enhanced best-fit-sphere (exclusion of a 4-mm diameter area from the most thinned cornea). The data correlated with the keratoconus severity index and Amsler-Krumeich classification of keratoconus. RESULTS: There was a significant positive correlation between elevation differences and keratoconus severity index in both anterior and posterior surfaces (Pearson correlation coefficient, r = 0.66; P < 0.001; r = 0.74; P < 0.001). Cases of larger elevation differences in the anterior and posterior corneal surfaces were staged higher in Amsler-Krumeich classification (1-way analysis of variance, P = 0.040; P < 0.001). Cases of lower staging in the Amsler Krumeich classification had a larger area under the receiver operating characteristic curve in the posterior elevation differences than in the anterior elevation differences, suggesting a greater diagnostic value of the posterior elevation measurement. CONCLUSIONS: Anterior and posterior corneal surface height data obtained by elevation-based tomography provide useful information in improving keratoconus diagnostic accuracy and in grading the severity of keratoconus. PMID- 22316651 TI - Ocular treatment of children with Stuve-Wiedemann syndrome. AB - PURPOSE: Stuve-Wiedemann syndrome is a rare condition consisting of bone dysplasia, hypotony, and dysautonomia with ocular and neuropathic features. We present the ocular findings and visual outcome in 4 patients (2 siblings, 1 related cousin, and 1 unrelated patient) with this syndrome. METHODS: A retrospective case series review. Clinical notes of 4 patients with Stuve Wiedemann syndrome were reviewed for findings of systemic features, ocular examination, visual acuity, and ocular procedures. RESULTS: The median age at presentation was 16 months (range, 14-72 months). All 4 cases consisted of bilateral plaque-like corneal scarring with reduced corneal sensation. Treatment comprised topical lubrication, punctal plugs, lateral tarsorrhaphies, surgical optical iridectomies when required, and aggressive visual rehabilitation with frequent refraction and occlusion therapy if necessary. Mean best-corrected visual acuity (BCVA) in the eye with best vision was 0.86 logarithm of the minimum angle of resolution (logMAR) (range, 0.72-1.1 logMAR) at presentation and 0.43 logMAR (range, 0.25-0.56 logMAR) at the last follow-up. The BCVA in the eye with worst vision was 0.98 logMAR (range, 0.72-1.3 logMAR) at presentation and 0.68 logMAR (range, 0.47-1.0 logMAR) at the last follow-up. The median follow-up was 3.2 years (range, 1.1-5.8 years). CONCLUSIONS: All of our patients showed improved BCVA with the treatment regimen prescribed. Given these children's debilitating orthopedic problems, visual function is important and has hitherto been reported as being poor. PMID- 22316652 TI - Pathogenesis of acute and delayed corneal lesions after ocular exposure to sulfur mustard vapor. AB - PURPOSE: Sulfur mustard (SM) exposure results in dose-dependent morbidities caused by cytotoxicity and vesication. Although lesions resulting from ocular exposure often resolve clinically, an idiopathic delayed mustard gas keratopathy (MGK) can develop after a moderate or severe exposure. Sequelae include persistent keratitis, recurring epithelial lesions, corneal neovascularization, and corneal degeneration, which can lead to impaired vision or loss of sight. The purpose of this effort is to correlate structural changes with injury progression during the development of MGK. METHODS: New Zealand White rabbit corneas were exposed to SM using a vapor cup delivery system. The transition from acute to delayed injury was characterized by clinical, histological, and ultrastructural metrics over 8 weeks. RESULTS: Exposure dose was correlated to the likelihood of developing MGK but not to its severity. In a 56-animal cohort, a 2.5-minute exposure generated a corneal lesion, with 89% of corneas developing MGK within 5 weeks. A significant decrease in corneal edema at 2 weeks was predictive of the 11% of corneas that underwent asymptomatic recovery. Ultrastructural comparison of asymptomatic and MGK corneas at 8 weeks indicates that MGK is characterized by persistent edema and profound disorganization of the basement membrane zone. CONCLUSIONS: Ultrastructural changes associated with the delayed pathophysiology of corneal SM vapor exposure involve severe degeneration of the basement membrane zone and persistent edema. The mechanisms underlying MGK pathogenesis seem to alter injury progression as soon as 2 weeks after exposure. These data suggest that the vapor cup model system is suitable for therapeutic evaluation. PMID- 22316653 TI - Toric intraocular lens in keratoconus. PMID- 22316655 TI - Vertebral fracture assessment by new dual-energy X-ray absorptiometry. AB - The aim of this study was to investigate the diagnostic performance of new dual energy X-ray absorptiometry (DXA) technologies in the detection of vertebral fractures (VFs). Sixty-eight patients were submitted to DXA and conventional radiography (XR) on the same day. Lateral images of the spine were independently evaluated by three radiologists with different experience in skeletal imaging, in two sessions with 7 days between evaluations of the same anonymous images. The most expert physician repeated the analysis in a subsequent reading session after further 7 days. Results from expert XR evaluation were considered as gold standard. A semiquantitative approach was used to interpret images and morphometric analysis was performed when a VF was suspected. Seventy vertebrae (70/884, 7.9%) were excluded from the lesion-based analysis, as not evaluable: 11/70 (15.7%) missed by XR only, 56/70 (80.0%) missed by DXA only, 3/70 (4.3%) missed by both techniques (upper thoracic spine). Forty "true" fractures were detected (4.9% out of 814 vertebrae) in 26 patients (38.2% of the 68 studied patients). Twenty-five (62.5%) were mild fractures. DXA sensitivity and specificity were 70.0% and 98.3% on a lesion-based analysis, 73.1% and 90.5% on a patient-based analysis. Intra-observer agreement was excellent with no significant difference between the two techniques. Inter-observer agreement among the 3 observers was higher for XR (k=0.824 versus 0.720 in the detection of VFs, p=0.011). DXA accuracy was not influenced by radiologist experience; T4-L4 assessability as well as reproducibility and repeatability of the two techniques and accuracy of DXA were independent from sex, age, body mass index, grade of arthrosis. However DXA sensitivity was affected by mild VFs. Vertebral level did not affect the diagnostic performance with exception of vertebral body assessability. Latest improvements make VFs assessment by DXA competitive with traditional radiographic gold standard, providing consistent advantages and attractions. Few limitations still affect DXA performance and need to be overcome. PMID- 22316656 TI - In situ imaging of the autonomous intracellular Ca(2+) oscillations of osteoblasts and osteocytes in bone. AB - Bone cells form a complex three-dimensional network consisting of osteoblasts and osteocytes embedded in a mineralized extracellular matrix. Ca(2+) acts as a ubiquitous secondary messenger in various physiological cellular processes and transduces numerous signals to the cell interior and between cells. However, the intracellular Ca(2+) dynamics of bone cells have not been evaluated in living bone. In the present study, we developed a novel ex-vivo live Ca(2+) imaging system that allows the dynamic intracellular Ca(2+) concentration ([Ca(2+)](i)) responses of intact chick calvaria explants to be observed without damaging the bone network. Our live imaging analysis revealed for the first time that both osteoblasts and osteocytes display repetitive and autonomic [Ca(2+)](i) oscillations ex vivo. Thapsigargin, an inhibitor of the endoplasmic reticulum that induces the emptying of intracellular Ca(2+) stores, abolished these [Ca(2+)](i) responses in both osteoblasts and osteocytes, indicating that Ca(2+) release from intracellular stores plays a key role in the [Ca(2+)](i) oscillations of these bone cells in intact bone explants. Another possible [Ca(2+)](i) transient system to be considered is gap junctional communication through which Ca(2+) and other messenger molecules move, at least in part, across cell-cell junctions; therefore, we also investigated the role of gap junctions in the maintenance of the autonomic [Ca(2+)](i) oscillations observed in the intact bone. Treatment with three distinct gap junction inhibitors, 18alpha glycyrrhetinic acid, oleamide, and octanol, significantly reduced the proportion of responsive osteocytes, indicating that gap junctions are important for the maintenance of [Ca(2+)](i) oscillations in osteocytes, but less in osteoblasts. Taken together, we found that the bone cells in intact bone explants showed autonomous [Ca(2+)](i) oscillations that required the release of intracellular Ca(2+) stores. In addition, osteocytes specifically modulated these oscillations via cell-cell communication through gap junctions, which maintains the observed [Ca(2+)](i) oscillations of bone cells. PMID- 22316657 TI - Extracorporeal cardiopulmonary support may be an efficient rescue of patients after massive pulmonary embolism. An experimental porcine study. AB - INTRODUCTION: Treatment of massive pulmonary embolism leading to cardiac arrest is controversial but restitution of circulation within a shorter time is crucial. Cardiopulmonary support and therapeutic hypothermia is an option for cardiac arrest and could be used to treat massive PE. However, hypothermia may influence the effect of the ongoing intrinsic fibrinolysis. OBJECTIVES: To establish a porcine model of massive pulmonary embolism, to show that cardiopulmonary support can rescue pigs with massive pulmonary embolism and to examine the effect of hypothermia on fibrinolysis. METHODS: Pigs ~80 kg were anesthetised and prepared for cardiopulmonary support. Repetitive injections of preformed blood thrombi into the right atrium were done until cardiac arrest. Cardiopulmonary support was established and eighteen pigs were randomised into 3 groups: Normothermia (38-39 degrees C); hypothermia (33-34 degrees C); or medication with recombinant tissue plasminogen activator. After three hours the pigs were weaned from cardiopulmonary support, and after 15 minutes with spontaneous circulation assassinated and autopsied. Remaining thrombi in the lungs were weighed. RESULTS: The development of fatal pulmonary embolism was highly reproducible. All 18 pigs could be weaned from cardiopulmonary support and survived more than 15 minutes. The amount of remaining thromboemboli was substantial in all groups and not significantly different between groups. Normothermic group 20.0 +/- 2.2 g, Hypothermic group 17.0 +/- 3.7 g, and rt-PA group 14.3 +/- 3.2 g. CONCLUSIONS: Cardiopulmonary support could rescue pigs with massive pulmonary embolism. Hypothermia did not reduce the emboli but may for other reasons be beneficial. The optimal additional treatment is still unknown but treatment modalities can be tested in this model. PMID- 22316658 TI - [Pretibial brown tumors as first manifestation of primary hyperparathyroidism]. PMID- 22316659 TI - [Hemolytic anemia secondary to Q fever]. PMID- 22316660 TI - [Syndrome of inappropriate antidiuretic hormone secretion in a patient treated with daptomycin]. PMID- 22316661 TI - [A novel therapeutical approach: remission of fibrosing diseases after intravenous high-dose bolus of methylprednisolone]. PMID- 22316662 TI - [Anemia in acute heart failure]. PMID- 22316663 TI - [Focused cardiac ultrasound in internal medicine]. AB - Focused cardiac ultrasound is a noninvasive technique which can be performed by the internist. It is capable of providing useful, rapid and accurate information about the structure and function of the heart. It can be used to complement anamnesis and physical examination at the bedside. Clinicians may be able to determine left and right ventricular diameter and function, detect the presence of significant pericardial effusion, identify important valvular defects and estimate the central venous pressure by measuring the diameter and collapsibility of inferior vena cava with good accuracy after a short training period. The aim of focused cardiac ultrasound is not to perform a complete echocardiogram but using previous mentioned data, it is possible to expedite diagnosis and optimize the management of patients with cardiovascular diseases. PMID- 22316664 TI - Reporting address changes by migrants: the accuracy and timeliness of reports via health card registers. AB - Up-to-date and accurate recordings of patient address are important in health services delivery, particularly for screening, immunisation and needs assessment of areas. Patients who change address are at greater risk of having an out-dated address registered with a health professional, which in turn can have a negative impact on their access to services and on the purported health needs of the areas they move to and from. The current study investigated the accuracy and timeliness of updated address information in the Health Card Registration System compared to self-reported addresses in the 2001 Census for members of the Northern Ireland Longitudinal Study (c508,000) who changed address during the years 2001-2007. Males, healthy people and owner-occupiers (level-one) and urban and more socially deprived neighbourhoods (level-two) were associated with an increased risk of late updating or non-reporting of address changes in a multi-level analysis. This may be explained by lack of engagement with the health service. Accurate address information could be considered as an indicator for the Quality and Outcomes Framework in the future in an attempt to maintain accurate records. PMID- 22316665 TI - TGF-alpha equalizes age disparities in stem cell-mediated cardioprotection. AB - BACKGROUND: Neonatal mesenchymal stem cells exhibit less cardioprotective potential than their adult counterparts. Transforming growth factor-alpha (TGF alpha) has been shown to stimulate adult stem cell VEGF production, however, it remains unknown whether it may augment neonatal stem cell paracrine function. We hypothesized that TGF-alpha would equalize adult and neonatal stem cell paracrine function and cardioprotection during acute ischemia/reperfusion. MATERIALS AND METHODS: Bone marrow mesenchymal stem cells isolated from adult and 2.5 wk-old mice were treated with TGF-alpha (250 ng/mL) for 24 h. VEGF, HGF, IGF-1, IL 1beta, and IL-6 production were measure in vitro, and cells were infused via an intracoronary route using a model of isolated heart perfusion. RESULTS: TGF-alpha equalized adult and neonatal stem cell VEGF production but did not affect production of HGF, IGF-1, IL-1beta, or IL-6. ERK, p38 MAPK, and JNK phosphorylation were greater in adult cells in response to TGF-alpha. Whereas infusion of adult but not neonatal stem cells was associated with improved myocardial functional recovery during reperfusion, infusions of either TGF-alpha pretreated cell group were associated with the greatest functional recovery. TGF alpha equalizes adult and neonatal mesenchymal stem cell VEGF production and cardioprotection in association with differential regulation of ERK, p38 MAPK, and JNK phosphorylation. PMID- 22316666 TI - The association of manganese superoxide dismutase expression in Barrett's esophageal progression with MnTBAP and curcumin oil therapy. AB - BACKGROUND: The aim of this study was to investigate the relationship between reflux induced bile insult and MnSOD expression, as well as to examine therapies to preserve MnSOD expression. Additionally, we sought to examine the relationship between MnSOD protein expression and MnSOD enzymatic activity. METHODS: MnSOD protein expression was determined by Western blot assay and enzymatic activity was determined by SOD assay. The enzymatic activity of the Het-1A and Bar-T cells were compared both before and after treatments. RESULTS: MnSOD expression in Het 1A cells was decreased after bile salt exposure. The cells that received MnTBAP or curcumin oil pretreatment showed increased MnSOD expression compared with control untreated cells. The Bar-T cells showed an increase in MnSOD expression after treatment with bile salts. The cells that were pretreated with MnTBAP displayed a larger increase in MnSOD expression compared with the cells that were not pretreated prior to bile salt exposure. The MnSOD activity was significantly different between the untreated cell lines (P = 0.01) and after treatment with bile salt (P = 0.03). Additionally, Bar-T cells had significantly less MnSOD activity than Het-1A cells after each of the pretreatments. CONCLUSIONS: We demonstrated preservation of MnSOD expression in Het-1A cells that were pretreated with antioxidants including MnTBAP, curcumin oil, and certain berry extracts. Additionally, we demonstrated that Bar-T cells have significantly less MnSOD activity than Het-1A cells. These finding have important implications for future studies regarding chemoprevention and the treatment of esophageal cancer. PMID- 22316667 TI - Germline mutations in SMAD4 disrupt bone morphogenetic protein signaling. AB - INTRODUCTION: Juvenile polyposis (JP) is an autosomal dominant disease that predisposes to GI malignancies. Germline mutations in the tumor suppressor gene SMAD4 account for approximately 20% of JP cases. SMAD4 is the common intracellular mediator of the TGF-beta and bone morphogenetic protein (BMP) pathways. Since mutations in BMP receptor 1A also cause JP, we hypothesize that altered BMP signaling is the underlying defect in JP. We therefore set out to investigate the effect of SMAD4 mutations on BMP signaling. METHODS: SMAD4 mutations identified in JP patients were selected for analysis. These were created in SMAD4 pCMV expression vectors (EV) using a PCR-based, site-directed mutagenesis (SDM) approach. SDM clones were confirmed by direct sequencing, then co-transfected with an IdI-BMP Luciferase Responsive Element (BRE-Luc) vector and Renilla control vector into HEK-293T cells. Lysates were then collected after 48 hours, and luciferase activity was quantified using a luminometer. A pCMV empty vector was used as a negative control, and its luciferase activity was considered the baseline for cellular BMP signaling. Results obtained for each SDM clone were compared to those with the wild type (WT) vector. Statistical analysis was performed with the Student's t-test. RESULTS: Eleven distinct mutations from 16 JP patients were analyzed; seven mutations were nonsense, and four were missense. Both type of mutations resulted in reduction of BMP signaling; missense mutations produced an 8-30% reduction in luciferase activity, whereas nonsense mutations led to 30-60% reduction in luciferase activity when compared to the WT clone (Figure 1). All nonsense mutations led to significantly reduced activity relative to WT (P < 0.05), while the reduction in signaling seen in missense mutations was not statistically significant. CONCLUSION: SMAD4 germline mutations as seen in the JP patients appear to negatively impact downstream BMP signaling. Nonsense mutations resulted in significantly reduced luciferase activity when compared to missense mutations. These results support the hypothesis that disruption of the BMP signaling pathway is the likely etiology of JP in patients with SMAD4 mutations. PMID- 22316668 TI - A technique of recipient portal venoplasty and cuff insertion for portal revascularization in orthotopic rat liver transplantation. PMID- 22316669 TI - Elderly recipients of hepatitis C positive renal allografts can quickly develop liver disease. AB - Our institution explored using allografts from donors with Hepatitis C virus (HCV) for elderly renal transplantation (RT). Thirteen HCV- elderly recipients were transplanted with HCV+ allografts (eD+/R-) between January 2003 and April 2009. Ninety HCV- elderly recipients of HCV- allografts (eD-/R-), eight HCV+ recipients of HCV+ allografts (D+/R+) and thirteen HCV+ recipients of HCV- allografts (D-/R+) were also transplanted. Median follow-up was 1.5 (range 0.8-5) years. Seven eD+/R- developed a positive HCV viral load and six had elevated liver transaminases with evidence of hepatitis on biopsy. Overall, eD+/R- survival was 46% while the eD-/R- survival was 85% (P = 0.003). Seven eD+/R- died during follow-up. Causes included multi-organ failure and sepsis (n = 4), cancer (n = 1), failure-to-thrive (n = 1) and surgical complications (n = 1). One eD+/R- died from causes directly related to HCV infection. In conclusion, multiple eD+/R quickly developed HCV-related liver disease and infections were a frequent cause of morbidity and mortality. PMID- 22316670 TI - Rapamycin induces heme oxygenase-1 in liver but inhibits bile flow recovery after ischemia. AB - BACKGROUND/AIMS: Rapamycin, which is employed in the management of patients undergoing liver surgery, induces the synthesis of heme oxygenase-1 (HO-1) in some non-liver cell types. The aim was to investigate whether rapamycin can induce HO-1 expression in the liver, and to test the effects of rapamycin on liver function in the early phase of ischemia reperfusion (IR) injury. METHODS: Isolated rat hepatocytes and a rat model of segmental hepatic ischemia and reperfusion were employed. Bile flow was measured gravimetrically or by using indocyanine green. mRNA and protein (by quantitative PCR and Western blot, respectively) and blood concentrations of rapamycin, bilirubin, and liver marker enzymes were measured. RESULTS: In isolated hepatocytes, rapamycin induced a 6 fold increase in HO-1, comparable to that induced by cobalt proporphyrin (CoPP), and a 2-fold increase in peroxiredoxin-1. Pretreatment of rats with rapamycin resulted in a small increase in liver HO-1 expression, a 20% inhibition of the basal rate of bile flow, and a 50% inhibition in the rate of bile flow recovery after ischemia. CoPP increased basal bile flow by 20% and inhibited bile flow recovery by 50%. These effects were associated with small increases in the blood concentrations of bilirubin and liver marker enzymes. CONCLUSIONS: Rapamycin, through HO-1 induction, has the potential to protect the liver against damage in the late phase of IR. The inhibition by rapamycin of bile flow indicates that its actions on liver function in the acute phase of IR injury are complex. PMID- 22316671 TI - Regeneration: letting the scaffold do the work. PMID- 22316672 TI - Effects of thyroid hormone supplementation on anastomotic healing after segmental colonic resection. AB - BACKGROUND: Alterations of thyroid hormones in colorectal surgery were previously studied. The aim of the present study was to determine the effects of triiodothyronine (T3) supplementation on anastomotic healing after segmental colectomy. MATERIAL AND METHODS: Thirty male Wistar albino rats were divided into sham (n = 6), control (n = 12), and experimental (n = 12) groups. Sham group rats were immediately sacrificed after segmental colonic resection. Control and experimental group rats underwent resection and anastomosis. Experimental group rats received a single dose of T3 (400 MUg/100 g) in postoperative day 1. Half of both control and experimental group rats were sacrificed on postoperative d 3 and the remaining half were sacrificed on postoperative d 7. Hydroxiproline (HP), myeloperoxidase (MPO), thyroid stimulating hormone (TSH), free T3 (FT3), and free thyroxine (FT4) levels, bursting pressure, and histologic analyses of the anastomotic segments were compared. RESULTS: FT3 levels significantly decreased in control groups rats compared with the sham group (P < 0.01). However, T3 hormone given rats had no decline in FT3 levels. Anastomotic bursting pressure was significantly higher in the experimental group rats on postoperative d 7 (P = 0.015). Histopathologic analyses of the anastomotic segments determined significantly more severe edema and necrosis in control group rats (P < 0.05). Collagen deposition in the anastomotic tissue was significantly higher in experimental group rats on postoperative d 7 (P = 0.015). CONCLUSION: Anastomosis after colon resection is associated with decreased FT3 level. T3 supplementation ameliorates the reduction in FT3 and seems to provide constructive therapeutic effects on anastomotic healing. PMID- 22316673 TI - Curcumin for the prevention of acute lung injury in sepsis: is it more than the flavor of the month? PMID- 22316674 TI - Working towards a better understanding of the biomechanics of the carotid artery. PMID- 22316675 TI - Increased JNK in males compared with females in a rodent model of abdominal aortic aneurysm. AB - BACKGROUND: In humans, there is a 4:1 male:female ratio in the incidence of abdominal aortic aneurysms (AAAs). c-Jun-N-terminal kinase (JNK) is an important upstream regulator of several enzymes involved in AAA formation, including the matrix metalloproteinases (MMPs). The purpose of this study was to determine if there is a gender difference between males and females in JNK during AAA formation. MATERIALS AND METHODS: Male and female C57/B6 mice underwent aortic perfusion with elastase or heat inactivated elastase with aortas harvested at d 3 and 14 for phenotype determination, RT-PCR, Western blot, and zymography. Additionally, in vitro experiments using siRNA were conducted to define JNK regulation of matrix metalloproteinases (MMPs). A t-test was used to compare between groups. RESULTS: Males formed larger AAAs at d 14 compared with females (P < 0.001), with significantly higher levels of JNK1 protein, proMMP9, proMMP2, and active MMP2. At d 3, males had more JNK1 mRNA, protein, and MMP activity. Knockdown of JNK 1 or 2 in vitro decreased MMP activity, while knockdown of JNK 1 and 2 together blocked all MMP activity. CONCLUSION: Alterations in JNK between genders is partially responsible for the differential rates of experimental AAA formation, likely through differential regulation of MMPs. PMID- 22316676 TI - Gender differences at the cellular level. PMID- 22316677 TI - Remodeling of extracellular matrix patch used for carotid artery repair. AB - BACKGROUND: We evaluated the in vitro strength and in vivo arterial-wall response to an extracellular-matrix-based patch material in a sheep model of carotid artery repair. MATERIALS AND METHODS: A six-ply sheet of acellular, porcine extracellular matrix (ECM) was subjected to in vitro material strength testing and implanted in 15 sheep for 30, 90, and 180 d. Bovine pericardium was used as a control in some animals. In vivo graft patency was assessed by angiography. Explanted grafts were evaluated by histopathology and burst-strength testing. RESULTS: Mean (SD) in vitro suture retention force of the ECM sheet was 14.5 (3.06) N; tensile strength was 29.7 (6.11) N; and probe burst strength was 185 (22.6) N. In vivo, mild stenosis was observed at 30 d for all patches; stenosis was absent at 90 d in the ECM-repaired arteries but not bovine pericardium controls. Pseudoaneurysm was not observed in any animal. Histopathology showed progressive graft degradation, collagen deposition, formation of neocapillaries and fibrocellular neointima, and endothelialization, but no calcification. Mean (SD) burst pressure for unrepaired arteries was 2608 (858) mmHg and 1473 (694) mmHg for ECM-repaired vessels. Mean change in diameter from unloaded state to burst pressure was 29% (9.7) for unrepaired vessels and 24% (13.4) for ECM repaired vessels. CONCLUSIONS: The six-ply ECM sheet can withstand the forces encountered after carotid artery repair. In sheep, it shows evidence of progressive, constructive remodeling as early as 30 d post-implantation with rapid deposition of endothelium. ECM shows promise as a patch material for CEA repair. PMID- 22316678 TI - Damage control resuscitation decreases systemic inflammation after hemorrhage. AB - BACKGROUND: Severe hemorrhagic shock and resuscitation initiates a dysfunctional systemic inflammatory response leading to end-organ injury. Clinical evidence supports the transfusion of high ratios of plasma and packed red blood cells (pRBCs) in the treatment of hemorrhagic shock. The effects of resuscitation with different ratios of fresh blood products on inflammation and organ injury have not yet been characterized. MATERIALS AND METHODS: Mice underwent femoral artery cannulation and pressure-controlled hemorrhage for 60 min, then resuscitation with fresh plasma and pRBCs collected from donor mice. Plasma alone, pRBCs alone, and ratios of 2:1, 1:1, and 1:2 plasma:pRBCs were used for resuscitation strategies. Mice were sacrificed to determine biochemical and hematologic parameters, serum cytokine concentrations, tissue myeloperoxidase levels, and vascular permeability. RESULTS: Compared with other resuscitation strategies, mice resuscitated with pRBCs alone exhibited increased hemoglobin levels, while other hematologic and biochemical parameters were not significantly different among groups. Compared with 1:1, mice resuscitated with varying ratios of plasma:pRBCs exhibited increased cytokine concentrations of KC, MIP-1alpha, and MIP-2, and increased intestinal and lung myeloperoxidase levels. Mice resuscitated with 1:1 had decreased vascular permeability in the intestine and lung as compared with other groups. CONCLUSIONS: Resuscitation with a 1:1 ratio of fresh plasma:pRBCs results in decreased systemic inflammation and attenuated organ injury. These findings support the potential advantage of transfusing blood products in physiologic ratios to improve the treatment of severe hemorrhagic shock. PMID- 22316679 TI - [A neonate with vesicopustular rash]. AB - We present a neonate with transient neonatal pustular melanosis, a benign skin rash seen in 0.2-2.2% of white neonates and in 4-5% of black neonates. Vesicopustular lesions are present at birth, the lesions rupture in 24-48 hours leaving hyperpigmented macules. These slowly fade in 3-10 weeks. PMID- 22316680 TI - [Diagnostic approach to hypocalcaemia and hypercalcaemia]. AB - A 49-year-old woman was examined for osteoporosis and metabolic bone disease after a low-trauma wrist fracture. Laboratory and additional radiological investigations revealed parathyroid hormone (PTH)-mediated hypercalcaemia caused by a parathyroid adenoma. A second patient, a 65-year-old woman with a history of abdominal complaints and tetany, appeared to have hypocalcaemia. Severe vitamin D deficiency and secondary hyperparathyroidism were detected and the patient was finally diagnosed with coeliac disease. Based on these case studies, we highlight the calcium homeostasis and the role of laboratory evaluation of serum calcium, inorganic phosphate, intact PTH, 25-OH vitamin D, magnesium and 24-hour urinary calcium excretion in the diagnostic work-up for hypocalcaemia and hypercalcaemia. PMID- 22316681 TI - [Reimbursement for alternative medical treatment in the Netherlands, incomprehensible]. AB - It is remarkable that, at a time when not only doctors but also the Health Care Inspectorate (IGZ) and the health insurance companies are paying increasing attention to the quality of conventional medicine, many alternative methods of treatments without a scientific basis are accepted in the Netherlands. Even though it has been conclusively demonstrated that most alternative therapies do not work and despite the absence of scientific proof of the safety and efficacy of alternative treatments, health insurance companies do often reimburse the incurred costs. Because the safety of alternative therapies is not guaranteed, these are neither in the interest of the patient nor of society. Moreover, they are associated with considerable costs for the individual patient. By reimbursing the costs of insufficiently proven treatments, the health insurance companies are applying double standards. Reimbursement for these therapies is made at the expense of other effective and proven treatments. This can be changed through the concerted efforts of policy-makers, doctors, the IGZ, and health insurance companies. PMID- 22316684 TI - Treatment of complex heavy metal wastewater using a multi-staged ferrite process. AB - Complete removal of heavy metal from complex heavy-metal wastewater (CHMW) requires advanced technology. This study investigated the feasibility of a multi staged ferrite process (MSFP) for treating CHMW, containing Cd, Cu, Pb, Cr, Zn, Ag, Hg, Ni, Sn and Mn. Our experimental results showed that most of the supernatants after conventional single-step ferrite process could conform to the effluent standard of Environmental Protection Administration in Taiwan. However, the sludge could not satisfy the toxicity characteristic leaching procedure (TCLP) limits due to high Cd, Cu, and Pb concentrations. The performance of MSFP in removing heavy metals from wastewater was subsequently investigated and the parameters of three treating steps in MSFP were optimized under 70 degrees C and 90 degrees C at pH 9, and 80 degrees C at pH 10. After the three-staged procedures, all heavy metals in supernatant and sludge could fulfill the contamination levels regulated by law. In addition, the sludge generated from the MSFP was examined by XRD and forms a stable spinel structure, which could be effectively separated by external magnetic field. PMID- 22316685 TI - Preparation and characterization of hydrophobic Pt-Fe catalysts with enhanced catalytic activities for interface hydrogen isotope separation. AB - Liquid phase catalytic exchange reactions are mainly used for separation of hydrogen isotopes from liquid water. Based on the carbon-supported Pt and Pt-Fe catalysts, different hydrophobic Pt and Pt-Fe catalysts were fabricated for use in such reactions. The characterization results indicated the Pt-Fe alloy was formed in the Pt(3)Fe/C catalyst prepared using a citric-acid-assisted NaBH(4) reduction method (CA-NaBH(4)). However, there were more Fe oxide species and the Fe components existed independently in the Pt(3)Fe/C catalyst prepared by the modified microwave-irradiated ethyl glycol reduction procedure (MI). Performance tests demonstrated that the activities of the hydrophobic Pt-Fe catalysts with appropriate Fe/Pt ratios, using the MI method, were enhanced because of the addition of Fe. In contrast, the hydrophobic Pt(3)Fe catalyst prepared using the CA-NaBH(4) method had lower catalytic activity than pure Pt. Possible reasons were explained by reaction mechanisms of double routes of LPCE catalysis. PMID- 22316686 TI - TG-MS study of the thermo-oxidative behavior of plastic automobile shredder residues. AB - Automobile shredder residues (ASR) are materials that are rejected in the metal recovery process for end-of-life vehicles (ELV). These residues are composed of such materials as plastics, foams, glasses, rubbers, textiles, remaining metals and soils. ASR disposal is a difficult task, due to increasingly restrictive re use policies. The pyrolytic reuse of ASR is one important option for energy recovery. The gas release behavior of pyrolyzed ASR was measured using a TG-MS apparatus, and this thermo-oxidative process was observed under different N(2)/O(2) volume ratios. The final weight/initial residue weight ratio for pyrolyzed ASR decreased from 43.4% to 10.1% with increasing oxygen concentrations. The production rates of hydrogen, methane and carbon dioxide also varied with different N(2)/O(2) volume ratios. The maximum emission of hydrogen and methane occurred when the thermo-oxidative atmosphere was entirely N(2). Temperature had a positive impact on hydrogen production, and the methane emission ratio reached a peak at the second shoulder of the devolatilization stage during which stage organic polymers were emitted. A peculiar characteristic of ASR is its content of nitrogen. The effects of ASR nitrogen content on N(2)O and NO(X) emissions were investigated in detail. NH(3) was the dominant nitrogen species that was released during ASR pyrolysis. N(2)O is highly temperature sensitive and decomposes to N(2) at temperatures greater than 900 degrees C. PMID- 22316687 TI - Assessment of the efficiency of photocatalysis on tetracycline biodegradation. AB - The use of photocatalysis to improve the biodegradability of an antibiotic compound, tetracycline (TC) was investigated. The toxicity of TC and its degradation products were also examined. The Sturm test was conducted to assess the biodegradability of by-products formed in the photocatalytic process. The toxicity of tetracycline and its by-products was evaluated using a dehydrogenase inhibition test, which showed a decrease in toxicity during photocatalysis. However, the Sturm test results indicated that, like tetracycline, the by products are not biodegradable. Possible structures of these by-products were determined using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). It was found that, during the photocatalytic process, the TC aromatic ring is not opened and the structure of the identified by-products is quite similar to that of tetracycline. A reaction pathway is proposed. PMID- 22316688 TI - Biodegradable and biocompatible epoxidized vegetable oil modified thermostable poly(vinyl chloride): thermal and performance characteristics post biodegradation with Pseudomonas aeruginosa and Achromobacter sp. AB - The increased production of municipal solid waste by the disposal of plastic materials heightens the urgency to develop biodegradable materials for daily use. In vitro-biodegradation study on poly(vinyl chloride) (PVC) plasticized by epoxidized Mesua ferrea L. seed oil at three different weight percentages (PVC/ENO ratio of 75/25, 50/50 and 25/75) was conducted by using Pseudomonas aeruginosa and Achromobacter sp. bacteria. The test bacterial species were able to grow on the polymer matrix by using it as a source of energy; however the pristine PVC did not support the microbial growth. The PVC/ENO material of 25/75 ratio showed the highest percent (%) of biodegradation compared to other tested systems. The bacterial count and the dry biomass post 180 days of inoculation in 25/75 plasticized PVC suggested bacterial growth at the expense of degradation of the system. The tensile strength of 25/75 PVC/ENO system, post 180 days of inoculation by Pseudomonas aeruginosa and Achromobacter sp. decreased by about 53% and 43% respectively. Further, surface erosion phenomenon and structural change of the matrix after bacterial growth, as studied by FTIR and SEM analysis of PVC/ENO of 25/75 ratio exhibited noticeable deterioration post 180 days of inoculation. PMID- 22316689 TI - Reprint of: Electrochemical oxidation of stabilized landfill leachate on DSA electrodes. AB - The electrochemical oxidation of stabilized landfill leachate with 2960 mgL(-1) chemical oxygen demand (COD) over a Ti/IrO2-RuO2 anode was investigated in the presence of HClO4 as the supporting electrolyte. Emphasis was given on the effect of electrolysis time (up to 240 min) and temperature (30, 60 and 80 degrees C), current density (8, 16 and 32 mAcm(-2)), initial effluent's pH (0.25, 3, 5 and 6), HClO4 concentration (0.25 and 1M) and the addition of NaCl (20 and 100 mM) or Na2SO4 (20 mM) as source of extra electrogenerated oxidants on performance; the latter was evaluated regarding COD, total carbon (TC), total phenols (TPh) and color removal. Moreover, the anode was studied by scanning electron microscopy and cyclic voltammetry. The main parameters affecting the process were the effluent's pH and the addition of salts. Treatment for 240 min at 32 mAcm(-2) current density, 80 degrees C and the pH adjusted from its inherent value of 0.25 (i.e., after the addition of HClO4) to 3 yielded 90% COD, 65% TC and complete color and TPh removal at an electricity consumption of 35kWhkg(-1) COD removed. Comparable performance (i.e. 75% COD reduction) could be achieved without pH adjustment but with the addition of 100mM NaCl consuming 20 kWhkg(-1) COD removed. PMID- 22316690 TI - Cysteinyl leukotrienes regulate TGF-beta(1) and collagen production by bronchial fibroblasts obtained from asthmatic subjects. AB - BACKGROUND: Cysteinyl leukotrienes (CysLTs) play an important role in airway inflammation in asthma but their role in airway remodeling is not completely known. METHODS: CysLTs receptors and procollagen I(alpha(1)) mRNA were determined by qPCR. Procollagen protein production was measured by RIA and TGF-beta(1) expression was determined by ELISA. TGF-beta receptor expression was assessed by western blots. RESULTS: CysLT1R, TGF-beta-R1 and active TGF-beta(1) are highly expressed in cells from asthmatics compared to normal controls. LTD(4) increased significantly procollagen I(alpha(1)) mRNA and protein expression in fibroblasts from asthmatics. This increase was blocked by CysLTs receptor antagonist. LTD(4) increased significantly mRNA expression of TGF-beta(1) and active form production in fibroblasts from asthmatics. Inhibition of TGF-beta(1) signaling blocked LTD(4)-induced procollagen I(alpha(1)) expression. CONCLUSIONS: Fibroblasts from asthmatic subjects express high level of CysLT1R. LTD(4) regulates procollagen I(alpha(1)) transcription in fibroblasts derived from asthmatic patients by modulating TGF-beta(1) expression. This suggests that CysLTs may play a role in regulating collagen deposition in asthma. PMID- 22316691 TI - New working conditions and consequences on activity of home healthcare workers. AB - Home healthcare is steadily growing in Europe. There are a number of reasons for this development: aging population, rising hospital costs, preference to stay in one's own home. Nevertheless, it has been known that home healthcare workers are frequently exposed to a variety of potentially serious occupational hazards. Furthermore, emotional labor is frequently high in this profession. This paper describes an ergonomic study conducted at a home healthcare service. The research focuses on analyzing working conditions of home healthcare aides and nurses, as well as the impacts of their work in terms of job satisfaction, well-being, emotions at work, relationships with the others and occupational stress. The study show that employee strategies are specifically centered around preserving the relationship between patients and workers and coping with the job demands. This paper also shows that home healthcare workers express emotions and conceal them from others. Finally, recommendations discussed with the manager and workers to improve working conditions in this sector led to practical proposals: for example, implementing certain equipment items better suited to difficult care, encouraging assistance between healthcare workers when operations require this through adequate organizational measures, extending work emotion-focused discussion groups with management involvement. PMID- 22316692 TI - Innovation in the occupational health physician profession requires the development of a work collective to improve the efficiency of MSD prevention. AB - Given the ageing population of occupational health physicians and the deteriorating situation of employee health, reforms targeting the multi disciplinary nature of occupational health are currently being drawn up. These are of great concern to doctors in terms of the future of occupational health, notably with regard to changing medical practices. The objective of this study is to explore the actual practices of occupational health physicians within the framework of MSD prevention in France. By analysing the activity of occupational health physicians, we could gain a better understanding of the coordination between those involved in OHS with the ultimate goal being to improve prevention. Based on an analysis of peer activity, this method made it possible to push beyond pre-constructed discourse. According to activity theories, it is through others that the history and controversies of a profession can be grasped and skills developed. The results produced by these collective discussions on activity analysis contributed to establish a collective point of view about the important aspects of their profession that need defending and the variations in professional genre in relation to the current reforms, notably. PMID- 22316693 TI - Efficiency of personal protective equipment used in agriculture. AB - Despite the practical importance of Personal Protective Equipment (PPE), both in production and in consumption, it is observed a main problem regarding the quality of many PPE?s used in Brazil. This study found a gap between the state of the art and the state of prevailing practices in the design of PPE?s, which main consequences affect the health of workers who use PPE in agriculture activities. The results of this study identified legal constraints of this occurrence, involving the validation of PPE designed for isolate agents, without the analysis of relevant activities and without prototypes experiments in more frequent use situation. PMID- 22316694 TI - The use of pesticides in French viticulture: a badly controlled technology transfer! AB - The use of pesticides is one of the techniques employed in modern agriculture and in particular in intensive agriculture. The risks for the environment and for worker health have been debated in western countries for about ten years. Recent developments in epidemiology, toxicology and ergotoxicology have clearly revealed that pesticides could harm the health of farmers (cancers, neurological diseases and reproductive disorders). Failures and shortcomings in the risk prevention systems have also come to light. This paper aims to address the risks associated to the use of pesticides in French vineyards. The chosen approach draws from an anthropological approach as well as from developments in ergotoxicology applied to the French vineyard work. We shall discuss the use of pesticides from the point of view of the transfer of technology. Our recent research has shown that this technology transfer was not completely controlled by the different stakeholders. PMID- 22316695 TI - Can activity be understood out of subjectivity? AB - The PSR echo a crisis of the relation of the organization with the subjectivity, which is at the same time a crisis of the relation of the organization with the reality that subjectivity is confronting through activity. Thus, they also raise, with ergonomics, the question to know which place it grants itself to subjectivity in the relation health-effectiveness. PMID- 22316696 TI - Contributions of ergonomics to the construction of bus drivers health and excellence in public transport and at work. AB - This article is the product of research that analyzed the work of bus drivers of a public transportation company that is considered a benchmark reference in its field of operations, in which it strives to achieve operating excellence. Within this context, the authors sought to understand how such a company has managed to maintain a policy that is capable of reconciling quality public transport while also providing working conditions compatible with the professional development, comfort and health of its workers. Ergonomic work analysis and activity analysis were the guiding elements used in this study. Initial analyses indicate that the activity of drivers includes serving a population and providing mobility for it, which depends on driving the vehicle itself and on relationships with colleagues, users, pedestrians, drivers and others. PMID- 22316697 TI - The 193 call center, a meaningful public service! AB - This article is the first part of an on-going ergonomic work analysis with the emergency services call center set up by the Fire Department of the Military Police of Sao Paulo. The final objective of the research is to identify the prescribed task, the real work executed and strategies used by workers to meet the demands of the job. Starting by identifying the tasks and activities developed, this article analyzes the work of the emergency services call center which is of vital importance to the organizational structure, since it is the start point for the process that results in fulfilling the corporation's mission. PMID- 22316698 TI - Organization of work in interaction between the paramedics and the patient. AB - The paper analyzes the ways in which the two paramedics organize their work activities in the courses of interaction with the patient. The paramedic-patient interaction is generally based on question-answer -sequences where one paramedic asks a question to which the patient answers. The paper examines the organization of paramedics' institutional roles and responsibilities within these particular sequences of talk by conversation analytic means. Instead of leaning on any personal or psychological explanations, the paper aims to demonstrate how particular breaches or problems in the organization of division of labour become explainable and understandable through the detailed analysis of preceding interaction. The main research data consist of the videorecordings of naturally occurring interactions between paramedics and patient. PMID- 22316699 TI - Working in verticalized platform vessel: an ergonomic approach in the oil industry. AB - In this paper we point some aspects of workers activities in offshore units in the oil industry. These units became more verticalized and have a greater number of operating systems. Our goal is to present the main difficulties that workers face in these units. PMID- 22316700 TI - Contributions from the activity analysis to the products development project: case study based on a project of innovation and comfort in aircraft's cabins. AB - Comfort is an issue that has gained relevance within the aeronautical industry due to the necessity of manufacturers and airline companies of differentiating themselves in a market that has become more and more competitive each day. This study's aim is to analyze the comfort/discomfort of passengers, based on the analysis of the activities performed in the aircrafts' cabin during real flights, in order to create ergonomics requirements and a methodology of comfort analysis. The study has been performed during domestic commercial flights, and the adopted data collection techniques have been: the application of 219 questionnaires to passengers, 44 registrations of postures and actions through filmings and 12 semistructured interviews. The method has made possible the reconstruction of the user's action course in performing activities in real flight situations, and the calculation of the area occupied by the passenger during his or her actions. The integrated analysis of the results corroborates data from previous studies in which both the space made available to each passenger and the activity performed interfere in their perception of comfort. From this study it has been concluded that the method constitutes itself as an innovative tool within the process of aircrafts' cabins project enabling the calculation of the action space based on the reconstructed course. PMID- 22316701 TI - Design of educational artifacts as support to learning process. AB - The aim of this paper is to identify utilization schemes developed by students and teachers in their interaction with educational workstations in the electronic measurement and instrumentation laboratory at the Department of Electrical Engineering in the Federal University of Minas Gerais (UFMG), Brazil. After that, these schemes were used to design a new workstation. For this, it was important to bear in mind that the mentioned artifacts contain two key characteristics: (1) one from the designers themselves, resulting from their experience and their technical knowledge of what they are designing and (2) the experience from users and the means through which they take advantage of and develop these artifacts, in turn rendering them appropriate to perform the proposed task - the utilization schemes developed in the process of mediation between the user and the artifact. The satisfactory fusion of these two points makes these artifacts a functional unit - the instruments. This research aims to demonstrate that identifying the utilization schemes by taking advantage of user experience and incorporating this within the design, facilitates its appropriation and, consequently, its efficiency as an instrument of learning. PMID- 22316702 TI - Coordination and artifacts in joint activity: the case of tagging in high-risk industries. AB - The social, organizational, and technological complexity of high-risk organizations creates a strong need for coordination. Joint activity in such systems thus relies both on formal coordination and on a set of informal coordinative practices. Coordinated joint activity is documented in this paper from two perspectives: the development of coordinative practices to overcome the limitations of formal coordination, and the use of artifacts for coordinative purposes. The empirical material is provided by a workplace study undertaken according to theoretical conceptions of situated action and cognition. It was undertaken in the context of a design project that aims at improving the tagout process in a high-risk industry. Findings first describe and analyze situations in which formal coordination turned out to be more of a constraint than a resource for effective action. They then illustrate the role played by artifacts in coordinated activity, focusing on the use of a particular artifact, the tagout tag, in different situations. PMID- 22316703 TI - The process of constructing new competencies in the family agricultural production unit. AB - This article discusses the difficulties dairy farmers face when they decide to install a new type of production on their units. We intend to discuss the nature of the new competencies the farmers will construct in order to install new production ateliers, and to show the complexity of the means they used, the difficulties they face in this process, and the strategies farmers develop in consonance with the practical knowledge of their profession. The method used was Ergonomic Work Analysis, together with semi-structured interviews, done after sessions of observation and work analysis. The results show that it is possible to apprehend a part of the complexity of the process of constructing competencies among dairy farmers, the diversity of kinds of resources they mobilize, integrate and transfer in this construction process that materializes through their activities in the work context. PMID- 22316704 TI - Finding disturbances in on-farm biogas production. AB - When implementing innovations, disturbances are very likely to take place. Disturbances are undesirable because they can lead to unwanted outcomes, such as economic losses and work overload to workers. However, they can be powerful opportunities for learning and re-designing innovations. Here, we will present activity theoretical tools for analyzing disturbances in a way that they could be used as learning opportunities. We illustrate the proposed tools by analyzing a disturbance that took place during the implementation of a project of biogas production. By interpreting the disturbance process with a network of activity systems, we found that on-farm disturbances were formed as ruptures, innovations and asynchronies originated in other activity systems. This finding suggests that disturbances are outcomes of the functioning of networks, rather than simple results of failure of individuals or technical devices. The proposed tools could be used in interventions to help practitioners and ergonomists to recognize the systemic and networked nature of problems, and therefore, realize that they may require the collaboration of actors from different activities. In this sense, disturbances may be turned into opportunities for learning and developing innovations. We conclude by discussing how the method could be used in ergonomic design and intervention. PMID- 22316705 TI - Activity at work, innovation and sustainable development. AB - The aim of this paper is to present and discuss a French-Brazilian project (CAPES COFECUB) centered on the relations between sustainable development, innovation and changes in work activities that accompany these innovations for sustainable development. Sustainable development calls for an integrated approach of three dimensions: social equity, economic viability and environmental sustainability. In order to achieve this integration, considerable innovations efforts are required. However, the work, understood as a productive act, is deeply lacking in the current researches. Starting from the idea that work is a "fundamental need" the goal of this project is to propose innovative methods that can be used for designing production systems from the perspective of sustainable development. PMID- 22316706 TI - The concept of contradiction in ergonomics practice. AB - The present communication deals with the methodology of the ergonomics field intervention process. It proposes an operationalized version of work analysis in terms of contradictions. The aim is to demonstrate that such a dialectic tool and method of representation may assist the ergonomist to frame the essence of a work activity in practical terms, swiftly and in a manner that preserves its multifaceted unity. The proposed method is inspired by two theoretical constructs (i) contradiction as used in Cultural Historical Activity Theory and (ii) regulation, as developed and used by the francophone tradition of ergonomics of activity. Two brief examples of its use are presented and a discussion is made on further developments and possible pitfalls. PMID- 22316707 TI - User-driven innovation of an outpatient department. AB - This paper presents experiences from a user-driven innovation process of an outpatient department in a hospital. The mixing of methods from user-driven innovation and participatory design contributed to develop an innovative concept of the spatial and organizational design of an outpatient department in a hospital. Design games and tabletop simulation seem to be powerful tools in facilitating such a participatory process. PMID- 22316708 TI - Ergonomics in projects of oil platforms in a change context. AB - The context of oil platform design is changing in order to increase competitiveness and be prepared for difficult operations, mainly in fields more distant from the coast, like pre-salt. The currently preceding context is marked by projects guidelines designed to reduce projects and operation costs, including an important reducing in the number of people on board. The main objective of this research is to verify and discuss if the experience of use in platforms designed in a previous context, in which the people on board is practically twice, can contribute and/or can be transferred to new projects. From the ergonomic intervention in the design of two oil platform, with the work of team on board investigated on previous projects as reference, it was possible analyze if the previous use is still applicable to new projects. As a result, about 90% of the recommendations based on use are applicable to the current context. The restrictions on the transfer or operational experience are mainly related to the time of entry of ergonomics in the design process, the subsequent transformations costs and the advance of the execution phase started with the detailed design. PMID- 22316709 TI - Expanding uses of building information modeling in life-cycle construction projects. AB - BIM is targeted at providing information about the entire building and a complete set of design documents and data stored in an integrated database. In this paper, we study the use of BIM in two life-cycle construction projects in Kuopio, Finland during 2011. The analysis of uses of BIM and their main problems will constitute a foundation for an intervention. We will focus on the following questions: (1) How different partners use the composite BIM model? (2) What are the major contradictions or problems in the BIM use? The preliminary findings reported in this study show that BIM has been adopted quite generally to design use but the old ways of collaboration seem to prevail, especially between designers and between designers and building sites. BIM has provided new means and demands for collaboration but expansive uses of BIM for providing new interactive processes across professional fields have not much come true. PMID- 22316710 TI - The use of participant-observation protocol in an industrial engineering research. AB - Based on literature, this article aims to present the "participant-observation' research protocol, and its practical application in the industrial engineering field, more specifically within the area of design development, and in the case shown by this article, of interiors' design. The main target is to identify the concept of the method, i.e., from its characteristics to structure a general sense about the subject, so that the protocol can be used in different areas of knowledge, especially those ones which are committed with the scientific research involving the expertise from researchers, and subjective feelings and opinions of the users of an engineering product, and how this knowledge can be benefic for product design, contributing since the earliest stage of design. PMID- 22316711 TI - Intermediary objects in the workspace design process: means of experience transfer in the offshore sector. AB - The aim of this paper is to discuss the use of intermediary objects in the workspace design process of offshore accommodations module. The integration of ergonomics in the design process can lead to better work conditions, more effectiveness in the work process and less health and safety issues. Moreover, it is more efficient in terms of cost if ergonomics is considered from the initial phases of the project, as the potential costs of the redesign, the possible losses and the down-time in the operation of the platform would be more increased. The goal, then, is to discuss the integration of ergonomics and users involvement in the design process of accommodations modules, focusing on the transfer of information from reference situations by the use of intermediary objects during the process. In this paper we will present two tools developed to be used as intermediary object(s) aiming at transferring the experience from the use to the design in the specific field of offshore accommodations module. PMID- 22316712 TI - Work situation operative model MOST: linking diagnosis and intervention to improve work conditions. AB - This paper presents the model "Work Situation Operative Model" - MOST (after its Spanish acronym). It offers a comprehensive, systemic approach to analysing work stations and/or work processes, serving also as a framework for pursuing various ergonomic and occupational health and safety goals. Originally produced for a food sector company, the model has been extended and successfully applied in several industries in Colombia and Ecuador, including cement, oil, and paper industries. Based on a systemic understanding of work systems and tasks, the model not only allows different, commonly-used methods and tools for evaluating or assessing the risk of muscular-sketetal disorders to be included, but also supports occupational risk management strategies. Hence, one of its more important contributions relies on providing meaningful information that is useful for improving the work station and/or work process through design and re-design, by focusing on the interactions between all system elements. PMID- 22316713 TI - The start up as a phase of architectural design process. AB - Alterations made in the architectural design can be considered as a continuous process, from its conception to the moment a built environment is already in use. This article focuses on the "moving phase", which is the initial moment of the environment occupation and the start-up of services. It aims to show that the continuity of ergonomics interventions during the "moving phase" or start up may reveal the built environment inadequacies; clearly showing needs not met by the design and allowing making instant decisions to solve non-foreseen problems. The results have revealed some lessons experienced by users during a critical stage not usually included in the design process. PMID- 22316714 TI - The realistic consideration of human factors in model based simulation tools for the air traffic control domain. AB - Advanced Air Traffic Management (ATM) concepts related to automation, airspace organization and operational procedures are driven by the overall goal to increase ATM system performance. Independently on the nature and/or impact of envisaged changes (e.g. from a short term procedure adjustment to a very long term operational concept or aid tools completion), the preliminary assessment of possible gains in airspace/airport capacity, safety and cost-effectiveness is done by running Model Based Simulations (MBSs, also known as Fast Time Simulations - FTS). Being a not human-in-the-loop technique, the reliability of a MBS results depend on the accuracy and significance of modeled human factors. Despite that, it can be observed in the practice that modeling tools commonly assume a generalized standardization of human behaviors and tasks and consider a very few range of work environment factors that, in the reality, affect the actual human-system performance. The present paper is aimed at opening a discussion about the possibility to keep task description and related weight at a high/general level, suitable for an efficient use of MBSs and, at the same time, increasing simulations reliability adopting some adjustment coming from the elaboration of further variables related to the human aspects of controllers workload. PMID- 22316715 TI - Analysis of the work of air traffic controllers of the approach control area (APP) of Porto Alegre, Brazil. AB - This article presents a study on the activities of the air traffic controllers of the Approach Control Area (APP) of Porto Alegre, Brazil, in different real scenarios. Based on interviews, questionnaires and the analysis of film of real scenes, the following were identified and analyzed: i) the perceptions of risk and complexity of the different air traffic scenes observed; ii) the cognitive factors (knowledge, strategy and attention dynamics) involved in the task and iii) the perception of the controller's workload. The results showed that the task complexity depends on the weather conditions, the number and type of aircraft in observation and that the controllers perceive the scenes in a similar way irrespective of their time in the profession and the type of control (radar or coordination). Attention is the cognitive factor with the greatest impact on the work and mental demand has the greatest impact on workload followed by time demand. The literature on the controllers work in Brazil is scarce and, therefore, this study aimed to contribute to the understanding of the work in one APP in order to promote future changes in the very problematic Brazilian air traffic system. PMID- 22316716 TI - Factor interaction influences on human performance in air traffic control: the need for a multifactorial model. AB - In air traffic management (ATM) knowledge of the impact of human factors on performance is critical to address safety incidents. Previous research has largely focused on the effects of single factors on performance which has resulted in a comprehensive understanding of single factor effects. In current control environments however, the residual threats for incidents often result from the interaction of multiple human factors and the resulting cumulative impact on performance. This research uses a literature review, an analysis of over 400 European aviation incident reports and finally a survey of ATM professionals to assess the need for a multifactorial model of performance. Literature findings suggest that Human Factors approaches are fundamentally single-factor in nature, which is out of step with real ATM working contexts. An incident report analysis, supported by a survey of air traffic experts, suggests that multiple factor incident causation exists. This discrepancy suggests the need for a new approach to looking at how incidents occur, and their factors managed, on a day-to-day basis. The proposed solution is a multifactorial model of human performance. PMID- 22316717 TI - Application of the user-centred design process according ISO 9241-210 in air traffic control. AB - Designing a usable human machine interface for air traffic control is challenging and should follow approved methods. The ISO 9241-210 standard promises high usability of products by integrating future users and following an iterative process. This contribution describes the proceeding and first results of the analysis and application of ISO 9241-210 to develop a planning tool for air traffic controllers. PMID- 22316718 TI - Air accident investigation among regulatory agencies. AB - The aim of this manuscript is to describe and compare regulatory aviation agencies according to their subordination and attributions to investigate air accidents. Possible consequences in identifying the contributory factors are also presented. Distinct procedures investigating air accidents among agencies lead to a lack of standardization of the statistics, making it difficult to analyze the data globally. Separately the information does not configure the entire scenario of what occurred, affecting the analysis and subsequent interventions. We recommend a joint and collaborative work between the different committees that operate in the investigation of air accidents. PMID- 22316719 TI - Manual flying skills under the influence of performance shaping factors. AB - This paper describes an experimental study investigating pilots' manual flying skills. In today's line oriented flight training, basic flying skills are neglected frequently. So, the study examines the manual flying skills of commercial airline pilots under the influence of several performance shaping factors like training, practice or fatigue in a landing scenario. The landing phase shows a disproportionate high percentage of aircraft accidents and it is typically flown by hand. The study is to be undertaken with randomly selected pilots in a full motion flight simulator to ensure a high validity of the results. PMID- 22316720 TI - Learning objects and training complex machines. AB - There are situations in the operation of complex machinery which is significant pressure. In need of capturing, interpreting and processing information from instruments, often in seconds. This occurs in the middle where it operates the pilot and the aircraft will be established a set of operations that will culminate with a maneuver, consisting of a substantial and binding set of procedures performed for this driver. This has little time to evaluate and act, supported by aircraft instruments and external environmental signals captured by the senses, which will stimulate conditioned actions that, if executed without due accuracy, is reflected in a deadly mistake. These situations cause a state of tension and unpredictability, especially when there is bad weather and / or no visibility and bad wind conditions occur and are not supportive or even shrinkage, or even partial or total ability to operate the airplane happen.. PMID- 22316721 TI - Application of diffusion maps to identify human factors of self-reported anomalies in aviation. AB - A study investigating what factors are present leading to pilots submitting voluntary anomaly reports regarding their flight performance was conducted. Diffusion Maps (DM) were selected as the method of choice for performing dimensionality reduction on text records for this study. Diffusion Maps have seen successful use in other domains such as image classification and pattern recognition. High-dimensionality data in the form of narrative text reports from the NASA Aviation Safety Reporting System (ASRS) were clustered and categorized by way of dimensionality reduction. Supervised analyses were performed to create a baseline document clustering system. Dimensionality reduction techniques identified concepts or keywords within records, and allowed the creation of a framework for an unsupervised document classification system. Results from the unsupervised clustering algorithm performed similarly to the supervised methods outlined in the study. The dimensionality reduction was performed on 100 of the most commonly occurring words within 126,000 text records describing commercial aviation incidents. This study demonstrates that unsupervised machine clustering and organization of incident reports is possible based on unbiased inputs. Findings from this study reinforced traditional views on what factors contribute to civil aviation anomalies, however, new associations between previously unrelated factors and conditions were also found. PMID- 22316722 TI - Could mild hypoxia impair pilot decision making in emergencies? AB - The decreased pressure in the cabin of a pressurised aircraft (typically equivalent to ~8000 ft) reduces the oxygen level so that the blood oxygen saturation of all occupants falls from >97% (normoxia) at sea-level to below 92% (mild hypoxia). Although exposure to mild hypoxia does not affect well-learned cognitive and motor performance of aircrew, it has been proposed that it can affect the performance of some complex cognitive performance tasks involving multiple demands typical of emergency tasks that may have to be performed by pilots. In order to simulate some of these complex cognitive demands, 25 student volunteers participated in an experiment which assessed performance of complex logical reasoning and and multiple memory tasks before and after 2 hours of exposure to normoxia and mild hypoxia. Performance for the more difficult components of the complex reasoning task, especially involving conflict decisions, were marginally significantly degraded by mild hypoxia. Since the effects were only marginally significant future studies should investigate the effects of mild hypoxia on more subtle complex decision-making tasks. PMID- 22316723 TI - The application of waste management systems for long duration spaceflight. AB - In the future planned interplanetary expedition mission to Mars, spaceflight crewmembers will be exposed to an environment that is completely unique from anything they are accustomed to on Earth. Due to the characteristics of these missions, a challenge will be to design an environment that allows crewmembers to easily work and live in for extended durations. One of the challenges associated with these future missions is supplying the crew with essential resources for survivability such as food and water. In this case, the waste management system can play a role in a closed-loop life support system, as provisions sent with the crew will be severely limited with no opportunity for resupply. The following looks at the rationale of designing a system for collecting, storing, and recycling human bodily waste that (1) is considered user-friendly by crewmembers in regard to habitability in spaceflight, and (2) provides applications for a self sustaining closed-loop life support system that will aid the crew during the mission. Future design processes should consider adhering to these guidelines to help in the spaceflight crew's living environment and the conduction of the interplanetary expedition. PMID- 22316724 TI - Achieving impact in ergonomic research. AB - People are central to system functioning and this role has been dramatically extended by new information technology. This makes possible the fundamental transformation of processes across systems of systems. Can Ergonomics research play an effective role in systems integration innovation? To have real world impact on such problems the system of R and D needs to sustain strong designs that address the functionality of socio-technical systems and support the implementation of innovations, taking into account the complexity of change, the importance of values of dignity and trust, and creating a common understanding amongst all stakeholders to enable design for operations. Strong research designs are more expensive, difficult, risky and prolonged than more commonly practiced weaker designs. They require active engagement with the industrial or service provider and involve overcoming cultural and other barriers to effective implementation and change. To create a virtuous cycle of research-generated impact it is necessary for strong designs to be well supported in the research community and for real world impact to be central to performance criteria of research excellence. Unfortunately neither of these criteria appear to be fulfilled. To ameliorate this, deficiencies in the full cycle of systems integration innovation need to be addressed. PMID- 22316725 TI - The passing of the shift in aircraft maintenance--a task that produces deaths. AB - Maintenance tasks, especially in heavy maintenance, may not be completed in a single shift. Aircraft maintenance technicians often take work in progress by colleagues, and spend the incomplete work for a change of team. The need for accuracy and efficiency of information transfer in many cases, without having time to have a meeting to pass the service is a crucial aspect of maintenance work. The ideal shift change can occur normally before delivery and continues to proceed normally after delivery. Although a shift change create challenges for communication, they also offer opportunities to detect and correct errors, where the task of delivery is an opportunity to identify the problem and fix it. In this case, the task was done correctly the first round, however, a problem began when the second round took. One example is a case in which the first round have removed a defective part for replacement and let the component of aircraft at end of turn with problems. Instead of ordering and installation of an operational component, the second round was then reinstall the faulty component, not realizing he had information about the problem attached. PMID- 22316726 TI - Automation under suspicion--case flight AF-447 Air France. AB - The probes allow the pilot to control the aircraft speed was essential to the balance of the flight. Opinions of experts who claim that "the design of the plane would have exercised a not inconsiderable role in the occurrence of a disaster." These messages revealed a series of important operating errors in a zone of turbulence, "making the plane uncontrollable, leading to a rapid depressurization device, according to these reports. A lawsuit in Toulouse and in Brazil aims to recognition of the liability of Air France and Airbus not insignificant role in the design and operation of the aircraft in the event of catastrophe. Opinions are taken from senior pilots that no commercial aviation training for certain situations abnormal flight that, if realized, could have influenced the pilots of the AF-447 to remove the plane's fatal dive show what experiments performed in simulators for military pilots, who are permanently subject to critical flight situations. PMID- 22316727 TI - Preliminary study of the pilot's workload during emergency procedures in helicopters air operations. AB - Military air operations and law enforcement operations in helicopters are examples of activities that require high performance of the operator. This article aimed at presenting a preliminary analysis of data obtained in the initial study in order to validate the instruments and the research protocol that focuses on the analysis of the workload imposed on helicopter pilots in emergency situations. The research was conducted in an environment of real flight training and used the NASA-TLX Scale to assess the workload and an interview guide to obtain reports on the main tasks performed. Preliminary data obtained is related to the participation of 10 (ten) volunteer pilots with experience in different types of helicopters. Four scenarios involving helicopter emergency procedures of HB-350 "Squirrel" were outlined. For this article, the analysis used only the data regarding the Physical and Mental Demands of the NASA-TLX Scale. Preliminarily, the results indicate that the "time pressure" as a factor contributing to increase mental requirement in emergency situations in flight, and that this increase was reflected in the request of mental processes such as: identification of the breakdown, attention and monitoring parameters. Future steps include extending the sample and adding physiological tools to better understand the effects of these types of emergencies on pilot performance and flight safety. PMID- 22316728 TI - Modeling activities in air traffic control systems: antecedents and consequences of a mid-air collision. AB - In this article we present a model of some functions and activities of the Brazilian Air traffic Control System (ATS) in the period in which occurred a mid air collision between flight GLO1907, a commercial aircraft Boeing 737-800, and flight N600XL, an executive jet EMBRAER E-145, to investigate key resilience characteristics of the ATM. Modeling in some detail activities during the collision and related them to overall behavior and antecedents that stress the organization uncover some drift into failure mechanisms that erode safety defenses provided by the Air Navigation Service Provider (ANSP), enabling a mid air collision to be happen. PMID- 22316729 TI - An approach to aircraft seat comfort using interface pressure mapping. AB - The objective of the present study is to propose a method to dynamically evaluate discomfort of a passenger seat by measuring the interface pressure between the occupant and the seat during the performance of the most common activities of a typical flight. This article reports the results of resting and reading studies performed in a simulator that represents the interior of a commercial aircraft. PMID- 22316730 TI - A first empirical investigation into the pleasure of control as explaining factor in usage durations of information systems. AB - To predict the technology acceptance of a system before market release is one of the big challenges of today. Many models are concerned with the question if someone is going to accept the system or not. Within this work a first empirical investigation of a personal trait called Pleasure of Control (PoC) is presented. Pleasure of Control is a construct that divides people into those people enjoy having control over a technical system and those who do not. It is predicted that a high Pleasure of Control leads to a prolonged system usage and unwillingness to accept highly automated systems. This paper presents a first empirical investigation of Pleasure of Control with 10 Persons with focus on usage durations. An experimental study revealed differences in the usage durations of a technical system (Apple iPad) between users with high and user with low Pleasure of Control measures. PMID- 22316731 TI - Subjective and objective evaluation of sense of space for vehicle occupants based on anthropometric data. AB - At present, the number of the vehicle requirements has been continuously increasing. These requirements can be related to the customer as well as the technical requirements. Among these, the "feeling of space" of the occupants inside the vehicles can be regarded as one of the most important factors. In this respect, the driver and passengers should be able to experience positive feeling of space inside the vehicle. There are numerous factors that can influence the sense of space inside the vehicle. These include geometry (vehicle dimensions), light exposure, ambient lights, colors, material selection and material surface. Depending on the selection, the sense of space can be dramatically influenced by these factors. In general, human feeling is subjective and cannot be measured by any instrument. The measure can nevertheless be carried out by utilizing the method of subjective evaluation. Throughout the experiments, the method of evaluation is developed and the factors which can influence the interior feeling are analyzed. In this process, psychological perception, architectural aspects and anthropometry are considered and knowledge from the other domains is transferred in the form of a multidisciplinary approach. The experiments with an aim to evaluate the overall sense of space in the vehicle are carried out based on the physical mock up of BMW 1 series (E87). The space perception with different interior dimensions and anthropometric data of test persons are also analyzed. The use of Computer Aided Technology was shown by CATIA V5, PCMAN and RAMSIS. The results show a good correlation between the subjective evaluation and the geometric values. PMID- 22316732 TI - The effect of system aesthetics on trust, cooperation, satisfaction and annoyance in an imperfect automated system. AB - Lack of system reliability has been repeatedly identified as a factor that decreases trust. However, aesthetics has an important role in the development of trust. Most of the research concerning the connection between aesthetics and trust focused on mobile commerce and websites while very little has been done in examining aesthetics in automated systems. This study integrated aesthetics manipulations into an imperfect in-vehicle automation system and focused on the power of aesthetics to decrease the negative effects of errors on trust, satisfaction, annoyance, and human-automation cooperation perceptions. Participants used the navigation system in either 100% or 85% accuracy levels with an aesthetic or non aesthetic system (4 conditions). In both aesthetic and non aesthetic systems, perceptions of trust, satisfaction and human automation cooperation were decreased in the imperfect system compared to the perfect one. However, in the annoyance rating, this trend was found only in the aesthetic system while in the non-aesthetic system no difference was found between the two levels of accuracy. This single effect may indicate upon the possibility that in automated systems aesthetics affects trust and satisfaction more moderately compared to mobile commerce applications and websites. However, more research is needed to assess this assumption. PMID- 22316733 TI - The perception of fear when using urban furniture. AB - This article presents a study on the perception of fear related to the use of three different types of urban furniture, qualitatively evaluated based on interviews while people were using them in the city of Porto Alegre, Brazil: the bus shelter, the playground, and the gymnastic equipment. The fear related to the lack of safety of the urban space was associated with the use of the three types of products. The fear experienced by the use of the playground and the bus shelter was related to the occurrence of accidents, since both products are often unsafe and do not fulfill ergonomic parameters. The fear experienced from the use of the gymnastic equipment is related to the possibility of incorrect use of the product and the occurrence of harassment. Both ergonomics and emotion are important aspects to be considered in design, in order to make the use of social/ collective products a pleasant experience. PMID- 22316734 TI - Personality of social robots perceived through the appearance. AB - Past research showed that people are able to perceive the personality of others at zero acquaintances. There are two main ways, verbal and non-verbal methods, which play an important role for one in perceiving personality of others. Extensive research was conducted in relating personality with verbal, paralinguistic and gestures cues. However, there are not much research, to our knowledge, that relates the appearance and perceived personality of robots. The main objective of this research is to relate individual design features with big five perceived personality of the robots. We used the results of rated perceptions across 100 pictorial images of robots and relate the results with the 40 individual design features using General Linear Model (GLM). The initial results of the GLM analysis showed that participants' rating of personality of robot fell along the dimension of perceived friendliness which is a common rotation of extroversion and agreeableness. Some relationships were found between humanlike design features and perceived friendliness of robots. Since participants are more familiar with humans, participants perceived robots with humanlike features friendlier than the others. Some other findings such as color and surface material were found related with participants' perceived friendliness as well. In the future, we will work on the analysis of the main and interaction effects of individual features on user's perceived friendliness. PMID- 22316735 TI - Usability and the emotional relationships in collective buying sites: a case study. AB - Several people buy products that they will never use or even know what for. Feelings associated with pleasure, spontaneity and possession of something are reasons why people buy products without considering if they really need it or not if it will be useful or not, etc.. The collective buying sites are going up and offer products and services with great discounts. This study aims to relate the emotional design and usability concerning to collective buying sites and identify the reasons that influence people when it comes to buy something online. PMID- 22316736 TI - The perception of pleasantness in a product of collective use: the bus shelter. AB - This article presents a study on the identification of a setting whose arrangement of attributes could lead to the perception of pleasantness of a bus shelter: a product that should welcome people while waiting for the bus. Two different bus shelters typologies in the city of Porto Alegre, state of Rio Grande do Sul, Brazil, were evaluated, where four attributes were under consideration. The relation between the shelters subject of the study and the surroundings was significant for defining the attributes. The setting with curve shaped cover, bench, rear wall, and surrounding vegetation was considered the most pleasant one. The seats and the rear wall were associated with the practical function of the product while the curve shaped cover and the surrounding vegetation were associated with the aesthetical function according to the participant users. PMID- 22316737 TI - Protection or pleasure: female footwear. AB - This article addresses the love for shoes by the perspective of design and emotion. Reviewing the footwear history, we realize that it did not take too long for the shoes start to have new functions, aesthetic and symbolic, which eventually came to have greater relevance in the acquisition of women's shoes. Today, these outweigh the importance of physical comfort for many women, that once feeling pretty, do not realize the discomfort of the shoe. Studies indicate that the objects we love have a strong influence on our sense of identity, especially when dealing with clothing articles that have the power to show on our appearance our identity, tastes and preferences. Crossing the semiotics field, the footwear is analyzed as an object of feminine desire, imbued with symbolic relations. As a result, we propose a framework to describe the emotional relationship between women and shoes. PMID- 22316738 TI - Comfort model for automobile seat. AB - Comfort on automobile seats is lived daily by thousands of drivers. Epistemologically, comfort can be understood under the theory of complexity, since it emerges from a chain of interrelationships between man and several elements of the system. This interaction process can engender extreme comfort associated to the feeling of pleasure and wellbeing or, on the other hand, lead to discomfort, normally followed by pain. This article has for purpose the development of a theoretical model that favours the comfort feature on automobile seats through the identification of its facets and indicators. For such, a theoretical study is resorted to, allowing the mapping of elements that constitute the model. The results present a comfort model on automobile seats that contemplates the (physical, psychological, object, context and environment) facets. This model is expected to contribute with the automobile industry for the development of improvements of the ergonomic project of seats to increase the comfort noticed by the users. PMID- 22316739 TI - Physical workload and thoughts of retirement. AB - The aim of this paper is to present Finnish employees' opinions on continuing work until retirement pension and after the age of 63, and to find out if physical workload is related to these opinions. Altogether 39% of men and 40% of women had never had thoughts of early retirement, and 59% claimed (both men and women) that they would consider working beyond the age of 63. Own health (20%); financial gain such as salary and better pension (19%); meaningful, interesting and challenging work (15%); flexible working hours or part-time work (13%); lighter work load (13%); good work community (8%); and good work environment (6%) were stated as factors affecting the decision to continue working after the age of 63. Employees whose work involved low physical workload had less thoughts of early retirement and had considered continuing work after the age of 63 more often than those whose work involved high physical loads. Own health in particular was stated as a reason to consider continuing work by employees whose work was physically demanding. PMID- 22316740 TI - Ergonomics of bridge employment. AB - In many countries of the world, retirement is mandatory at the age at which persons who hold certain jobs or offices are required by employment law to leave their employment, or retire (60 to 65 years). Typically, this is justified by the argument that certain occupations are either too dangerous or require high levels of physical skills and mental work. Every worker has to leave the workforce at that age. However, starting from the last two decades of the last century, it is observed that retirees live more years in retirement than ever before. This relatively long retirement as well as retirees' body fitness made many of them engage in new jobs which are either similar to their career jobs, or completely different from them. In this new type of employment which is called "bridge employment', the retired worker may spend more than ten years. But, to what extent these new jobs are fitted to the aged worker? Considering that experiencing any type of event increases the risk of worse health outcomes over time, bridge employment should be ergonomically designed if it is to fit the aged worker characteristics (physical, mental and affective). PMID- 22316741 TI - High work ability in the scientific activity of older and experienced academics. AB - At present the health of people in theirs 60s is the same as in theirs 50s around fifty years ago. Using older academics is a topical problem for universities in remaining efficient. Data regarding academics' scientific productivity at universities were collected and questionnaires compiled in the Faculty of Economics and Business Administration of Tallinn University of Technology in Estonia. Studies showed that the productivity of academics at university increases as they grow older (into their 60s). These academics are valuable to the university. The choice of academics should be made according to the candidates' knowledge and ability to work. PMID- 22316742 TI - Work ability among nursing personnel in public hospitals and health centers in Campinas--Brazil. AB - Nursing personnel is essential in hospital, health centers and enterprises and is the large work force in health system. A cross-sectional study was conducted in a large city in two public hospitals and five health centre with the objective of to evaluate the work ability and health aspects of nursing staff. The sample was composed by 570 workers. The Work Ability Index - WAI and a questionnaire with socio-demographic, health and life style data was applied. The majority of workers was women (83%), married (50.4%), and was working in night shift work (65.6%); 61.4% was auxiliary nursing, 22.3% was registered nurses (RN). The average age was 38.9 years (SD 7.8) and the Body Mass Index mean was 25.8 (SD 5.3). Only 17.2% referred to practice at least 150 minutes of physical exercise five times per week or more. 26.8% had a second job. The work ability mean was 39.3 (SD 5.3) points. Age had a negative correlation with WAI (p=0.0052). Public hospital and health centre workers had poor work ability score when compared with workers from another branches. Public policies related to workplace health promotion need to be implemented in public hospital and health centre to improve the work ability. PMID- 22316743 TI - Mobile phones and elderly people: a noisy communication. AB - Knowing the users is capital for building user-friendly digital interfaces. One way to think about the users is considering their familiarity with this technology. This article presents the results of twelve interviews with elderly people residing in the so-called South Zone of Rio de Janeiro (Brazil) who have used mobile phones over at least one year. It is part of the Doctor's Thesis "Mobile phones for elderly people - usability for social integration" ("Celulares para idosos - usabilidade a servico da integracao social"), which is targeted at ascertaining if the current mobile phones are user-friendly for elderly people. Through the technique of Guided Interviews, we found usage time, criteria for choice of phones, reasons for changes, preferences, and manners of use. Preliminarily, we have noticed differences in the behavior of the participating users and performed a qualitative analysis according to groups of age and gender. PMID- 22316744 TI - Application and analysis of the affinities diagram on the examination of usability problems among older adults. AB - Older adults have been facing usability problems every day, and with the increasing of life expectation those issues will be more and more frequent. The study of this group capacities and limitations could help designers to project systems more usable to everyone. PMID- 22316745 TI - Development of guidelines for designing appliances for older persons. AB - The ability of older adults to use a domestic appliance depends on their comprehension of the appliance's operation. This may depend on transfer of understanding from similar, more familiar technology. While this may assist their interaction with the new device, it may constrain the discovery of new functionality not represented in the familiar technology, and, thereby, constrain the discovery of advanced functionality. Older adults experience declining cognitive abilities associated with attention, perceptual encoding, and memory (cueing and recall). Designing appliances to extend cognitive abilities provides opportunity to prolong functional independence. Concepts from cognitive psychology, human factors, and gerontology are reviewed to explain age-related behavior towards technology to support innovative product development of technologies for older adults. PMID- 22316746 TI - Process of precocious functional aging in workers of laundries. AB - The World Health Organization (WHO), as well as researchers of the whole world, it has been demonstrating concern with the subject of the aging related to the work and it recognizes that modifications in the several systems of the human body take to the gradual decrease in the effectiveness of each one of them, because the aging caused by the work advances apprenticeships of the cycle of the man's life, not respecting the natural state of that process. In this sense, it was aimed at with this research to investigate the relative aspects to the capacity for the work and to the workers' with responsibility to realize the work in the laundries service, verifying if they present signs of precocious functional aging. PMID- 22316747 TI - A usability gap between older adults and younger adults on interface design of an Internet-based telemedicine system. AB - Internet-based telemedicine is becoming an effective tool to deliver home healthcare services and health information on demand, especially in rural areas, where there is often a large elderly population with greater rates of preventable chronic diseases. However, the designs of current interfaces for these internet based telemedicine systems do not take elderly user characteristics into consideration. This study conducted usability testing on the interface of an internet-based telemedicine system using two different age groups, young adults and older adults. Differences in overall performance and satisfaction between the two groups were identified. Based on these results, a future direction is suggested for the interfaces of Internet-based telemedicine systems. PMID- 22316748 TI - A suggestion for future research on interface design of an Internet-based telemedicine system for the elderly. AB - Telemedicine has emerged as an effective tool for providing high quality healthcare service and health-related information, especially in rural areas. Rural areas often have a larger elderly population with greater rates of preventable disease. These areas also have fewer medical resources and specialists, and have limited access to health services, all of which can influence overall health. An Internet-based telemedicine system can be one solution to provide the rural elderly with the proper health information when needed. The elderly obviously have limited capabilities compared with younger adults in the use of internet technology. However, the interfaces of the currently existing Internet-based telemedicine systems are not specifically developed for elderly users. This paper suggests future interface design research for an Internet-based telemedicine system specifically for the elderly. PMID- 22316749 TI - The relevance of temporal iconicity with instruction manuals for elderly users. AB - Gerontolinguistic obtains a growing importance with the increase of elderly users due to Demographic Change. Since acceptance and ease of use of supportive systems for elderly, such as "E-Nursing-Assistants", are highly dependent on the age suitable design of readable instructions, an age-appropriate linguistic concept is of high value for usability. There has been only little research on the relevance of foreign words, signal words, textual arrangement, optical accentuation of key terms and temporal iconicity concerning older users. Thus, an efficient design of age suitable manual instructions within a medical context still remains to be done. The objective of this research was to evaluate the relevance of the previously mentioned factors in the context of written instructions. For this, an empirical survey was designed which was given to 45 study participants. The subjects of the experiment were given 4x3 instructions after a pretest questionnaire. The aim was to execute these instructions as correctly and quickly as possible. Furthermore the instructions were rated regarding comprehensibility with a retrospective questionnaire. PMID- 22316750 TI - Elderly-technology interaction: accessibility and acceptability of technological devices promoting motor and cognitive training. AB - As the world population is ageing, studies on the socio-economic and health consequences are proliferating. Little has been done on the effectiveness and impact elderly may benefit from the use of technology in their everyday life. The pilot study, implemented within a funded project aimed at identifying sustainable actions to promote Seniors' quality of life, intended to investigate this kind of interaction in terms of accessibility and acceptability that senior citizen experience with technological devices promoting motor and cognitive training. In the hypothesis, interfaces and technological artifacts, that still take in little account the seniors' physical characteristics (e.g. physiological limitations in sight, hearing, movement) and cognitive processes (selective memory often driven by practical needs), can cause elderly to mistrust technology. Study participants were twenty over seventy-year-old people, who were observed and interviewed in context in a two-hour training session regarding the technological devices user experience. The results are presented with scenario-based techniques that help represent typologies of users in different use situations. Findings confirm the hypothesis, highlighting that elderly may accept technological artifacts when they perceive them as bringing benefits in terms of well-being and health. PMID- 22316751 TI - Age differences and transfer on control solution testing with blood glucometers. AB - The elderly are at an increased risk for being diagnosed with diabetes. While previous studies have examined technique errors when a patient used his or her current blood glucometer or a single novel glucometer, no study has measured errors as a patient transferred to using a second, novel experimental glucometer. Results support findings that older adults perform more slowly and less accurately than younger adults when transferring between pieces of equipment. Implications for future blood glucometer design and training are discussed. PMID- 22316752 TI - Universal design and accessibility: an approach of the influence of muscle strength loss in the risk of falls in the elderly. AB - This study was conducted with older adults living in a long-stay institution in the city of Foz do Iguacu, Parana, Brazil with the objective of assessing the influence of muscle strength loss in the risk of falls. The sample consisted of 65 elderly who walk without the aid of support for locomotion, 37 women and 28 men, aged between 67 and 80 years. The risk of falls was assessed through the TUG test. To determine the handgrip strength, a hand dynamometer model Jamar ( was used, which provides the result in kg / force (kgf), being held only with the dominant hand. The results showed that in the last 12 months, only 32% of the elderly surveyed had no fall and the average handgrip strength was 24.32 ( 11.22 kgf; 40% had one fall and the average handgrip strength was 23.82 ( 10.18 kgf; 8% had two falls and the average handgrip strength was 19.48 ( 8.21 kgf and 20% had more than one fall and the average handgrip strength of 18.13 ( 7.33 Kgf., indicating that the force levels are statistically lower among elderly at high risk of falls (p> 0.05). It was concluded that the lower the force level, the greater the likelihood of falls. Thus, it is important to stress that due to the loss of muscle strength, all ergonomic hazards and architectural barriers must be removed so that older adults can perform their tasks more easily, with comfort and safety. PMID- 22316753 TI - Ergonomics as a tool in prolonging youth and postponing ageing. AB - The EU and its Member States have identified population ageing as one of the key economic and social challenges to be faced. A high employment rate for older workers is essential. The ability to work is a prerequisite for a high employment rate for older workers. From 1965-2000, we carried out physiological and ergonomic studies in enterprises in Estonia, Russia, Ukraine and Moldova and proposed measures to avoid health risks. Our investigations were commissioned by industrial enterprises to improve the workplace and working conditions. The most interesting finding was that it was possible to markedly postpone the development of ageing changes in workers' bodies by up to 20 years without major investments. PMID- 22316754 TI - An ergonomic approach to improve work conditions of older employees in social housing. AB - French companies are legally required to develop action plans to improve employment and work conditions for older workers ("plans seniors"). These plans contain measures oriented towards recruiting, career evolution, skills developme1nt, knowledge transmission and improvement of work conditions. A tool for assessing work situations experienced by council buildings caretakers ("gardiens") was used in such a plan on behalf of the main agency of council housing in Paris, and we developed. This assessment tool was developed after ergonomic work analysis on a sample of 36 older caretakers (age > 57 y.o). The technical inspectors in charge of technical interventions on buildings and managing caretakers were trained to use the assessment tool and apply it to all caretakers aged 50 and over. PMID- 22316755 TI - A polynomial equation to predict low back compression force: accounting for the effects of load height on instability. AB - The purpose of this study was to develop a regression equation that, incorporating the potential energy of the load in the hands, was capable of improved predictions of spinal compression forces. A stepwise polynomial equation was developed from EMG profiles of 15 muscles, and its spinal joint loading predictions at L4/L5 were compared to current methods of calculating spinal compression. Absolute muscle activation was shown to increase with increased loading height, indicating that the central nervous system responds to changes in spinal stability. The inclusion of potential energy into the calculation of spinal disc compression at L4/L5 improved estimates of the compressive forces acting on the spine. This is the first model to incorporate potential energy into a predictive model for lumbar spine compression without the use of electromyography. It was concluded that potential energy plays a vital role in dictating the recruitment patterns of the trunk. PMID- 22316756 TI - Interaction between employees' physical load factors and early support at the workplace. AB - Physical workload is a continuous problem, even in modern workplaces. The purpose of the survey was to determine the effect of support on employees' physical load factors at workplaces. Training, guidance and support were the main focus areas of the early support intervention, which aimed to enable supervisors to find weak signals of impaired ergonomics.The survey was carried out in the form of a controlled longitudinal study, and the material was gathered via a questionnaire in both 2008 and 2010 from two co-operative trade groups. The final sample was 301 intervention subjects and 235 control subjects, and the response rate was 45% in both groups. We applied factor analysis to reduce the number of items. The physical load factors' sum score consisted of six items. We used logistic regression in the statistical analysis.Encouragement to improve processes at the workplace increased the probability of positive change (i.e. decrease) in physical load factors. The same applied to working pace, if individuals could control it themselves. In contrast, workload and the support of supervisors had a reversed impact on workers' physical load factors. Focusing on promoting workers' ergonomics is still important in workplaces when aiming to decrease physical load factors. PMID- 22316757 TI - An equation to predict maximum acceptable loads for repetitive tasks based on duty cycle: evaluation with lifting and lowering tasks. AB - Recently, an equation was developed to predict maximal acceptable effort (MAE) for repetitive tasks based on the product of task frequency and effort duration (ie. duty cycle). This equation has been shown to closely match data from psychophysical studies of the upper extremities. In the current paper, the applicability of this equation was tested on lifting and lowering data from Snook and Ciriello (1991) and was found to fit closely, even at very low duty cycles. PMID- 22316758 TI - Ergonomic intervention in aonla pricking operation during preserve preparation in food processing industries. AB - Aonla is an important Indian fruit crop with great potential for processing into various quality products. Aonla preserve making is an important economic activity in our country. The pricking methods are age old, hence a hand operated aonla pricking machine was introduced in preserve making industries to speed up the pricking task. OWAS and RULA two of the most commonly used ergonomic assessment tools were evaluated for their efficacy in the assessment pricking along with Rating of perceived exertion scale. Analysis of working posture using RULA revealed that the pricking task with existing methods i.e. fork and hand tool requires immediate investigation and changes in working posture while with machine pricking investigations and changes are required soon. The results of OWAS indicated that the posture maintained while pricking with existing methods need to be changed in future planning while with machine was acceptable. The subjective assessment revealed that machine pricking was less exerting activity as compared to the existing methods. The preserve prepared from machine pricked fruit was most acceptable among consumers. Hence, in the form of machine ergonomic intervention was brought about in preservation industries which have proved beneficial for workers in terms of their safety and productivity. PMID- 22316759 TI - Assessment of physical workload in boiler operations. AB - The use of boiler wood-fired is fairly common equipment utilized in steam generation for energy production in small industries. The boiler activities are considered dangerous and heavy, mainly due to risks of explosions and the lack of mechanization of the process. This study assessed the burden of physical labor that operators of boilers are subjected during the workday. Assessment of these conditions was carried out through quantitative and qualitative measurements. A heart rate monitor, a wet-bulb globe thermometer (WBGT), a tape-measure and a digital infrared camera were the instruments used to collect the quantitative data. The Nordic Questionnaire and the Painful Areas Diagram were used to relate the health problems of the boiler operator with activity. With study, was concluded that the boiler activity may cause pains in the body of intensity different, muscle fatigue and diseases due to excessive weight and the exposure to heat. The research contributed to improve the boiler operator's workplace and working conditions. PMID- 22316760 TI - Physical demands during the hauling of fishing nets for artisan fishing using rafts in beach of Ponta Negra, Natal--Brasil. AB - The current article aims to analyse the activity and the repercussions in the health of the artisan fishermen who use rafts in the urban Beach of Ponta Negra in Natal - RN, with emphasis on the physical demands at the step of hauling the nets from the ocean. It has been taken as a reference the methodology of Work Ergonomic Analysis-WEA. 21 fishermen participated in the study (50% of the population). It was used applying observational techniques and methodologies (open and sistematic observations and simulations) interactional ( social and economic questionnaire, conversational actions, verbalizations, self confrontations and collective analysis) and health assessment (static postural assessment, movement flexibility of flexo extension of the shoulder and the ischiotibial muscle, lumbar region and hang grip. Applying the diagram of painful areas and the Nordic Questionnaire of mucleskeletal symptoms). The results were submeted to restitutions and validations with the raftmen. The hauling of the nets represents a high muscleskeletal risk, joining physical effort, adopting forced postures with the rotation of the spine and movement repetition, mainly flexo extension of vertebral spine, aggravated by the demand of strength fo the stabilizing muscles of the human body to keep the poise. The impacts of the activity of the fisherman of Ponta Negra, related to postures and strength demand were observed in the postural assessment and are related to the activity. PMID- 22316761 TI - The effects of functional limitations on soldier common tasks. AB - This paper describes the findings associated with the ability of an individual to perform the United States Army's Common Soldier Tasks of: "Maintaining an M16 Series Rifle" , "Protect Yourself from Chemical, Biological, Radiological, and Nuclear (CBRN) Injury or Contamination with Mission-Oriented Protective Posture (MOPP) Gear", and "Protect Yourself from Chemical and Biological (CB) Contamination Using Your Assigned Protective Mask." The analysis was conducted using data compiled from videos of a Soldier performing the given tasks at Walter Reed Army Medical Center. The findings reflect the opinions of researchers in identifying potential elements, which impose abnormal, irregular, and/or extraneous effort when performing the tasks as outlined in STP-21-1-SMCT - Soldier's Manual of Common Tasks: Skill Level I. PMID- 22316762 TI - Physical workload during firefighting in Chilean volunteers. AB - The study was performed in a sample of 39 firemen. The state of health for each fire fighter was evaluated by means of a clinical examination and also through some specific exams. Aerobic capacity was estimated as an indicator of physical fitness. In each load, cardiac frequency and oxygen consumption were measured under a steady state condition. Additionally, body composition was calculated using a Tanita professional scale. Physical effort at work was determined by measuring cardiac frequency using a telemetric unit. Evaluations were carried out during night shifts, registering information under the following conditions: night shifts without emergency, fire simulation, training exercises and real fire fighting. In general terms, it is possible to state that fire fighters are healthy according to the result of the clinical examination. However, it is very important to highlight that 70% of the firemen consume alcohol and 80% were smokers. The average aerobic capacity of the sample was 2.6 l/min or 34.5 ml/kg/min. In terms of overweight and obesity, the body mass index was 25.7, whereas the percentage fat mass reached an average of 22.9 %. The cardiovascular load in the night shifts without emergencies did not surpass 40%, which in Chile is considered the highest limit for sustained work. However, during training, simulations and real fires, the firemen had higher cardiac frequencies, reaching peak levels close to 100% cardiovascular load. PMID- 22316763 TI - The cognitive ergonomics and the articulation of the functions of industrial products. AB - The sustainable development is a challenge to all areas of knowledge. In the field of design, it motivates an enhanced discussion about the functions of systems, products and services. Accordingly, this paper presents a theoretical contribution to the sustainable articulation of the functions of industrial products from principles of cognitive ergonomics. This paper is based on an exploratory literature about the functions of industrial products and further study of the relationship between man and object of Cognitive Ergonomics, specifically linked the aesthetic perception and symbolic. Presents qualitative results of this correlation, which indicates the feasibility of a better articulation in product development. The paper argues that in the practical field of design, the best articulation of the functions may influence the effectiveness of product performance in its relationship with the user. Already, on theoretical grounds, this new articulation can help designers to understand the nature of the transdisciplinary functions and the insights into product design. PMID- 22316764 TI - Physiological stress assessment of female workers at kitchen workstation. AB - This paper explores the extent of the physiological stresses of female workers at kitchen workstation while performing the various activities. For this a survey of eighty homemakers and experiment on sixteen respondents having similar physical and physiological parameters was done. Five activities in which the respondents faced maximum problems were selected and were standardized. Physiological stresses including cardiovascular, muscular, and energy expenditure during these activities were then assessed. Study revealed that fatigue during the selected five activities i.e. cutting, grating, rolling, kneading, dish washing, was felt mainly at the wrist, fore arm, followed by discomfort in the shoulders, upper arm, lower back and neck. Energy expenditure for these activities ranged from 7.0 to10 kJ?min, total cardiac cost of work (TCCW) was between 200.81 to 364.30 beats, physiological cost of work (PCW) was 12.82 to 26.26 beats?min; maximum for grating and minimum for rolling. The percent increase in heart rate was maximum for grating 38.56 and minimum for rolling 16.20. Reduction in grip and pinch strength of right hand was found more as compared to the left hand. PMID- 22316765 TI - Level of self-reported neck/shoulder pain and biomechanical workload in cleaners. AB - The aim of the present study was to investigate the relation between self reported pain, muscular activity and postural load during cleaning tasks. Eighteen cleaners performed usual cleaning tasks in both a laboratory and a lecture room. The level of perceived pain in the neck-shoulder region during the last 7 days was recorded. Bipolar surface electromyography (SEMG) was recorded bilaterally from upper trapezius and erector spinae muscles during cleaning. Root mean square (RMS) and permutation entropy (PE) values representing amplitude and complexity of SEMG time-series were estimated. A tri-axial accelerometer package was mounted on the low back (L5-S1) to measure postural changes during cleaning tasks. The 10th, 50th and 90th percentiles of the angular distributions were computed to characterize postures and movements. Pain tended to play a significant role on RMS of left/right trapezius and left erector spinae muscles (P<=0.08). Cleaners with low pain level exhibited higher muscular activity during cleaning. Pain played or tended to play a significant role on PE of left and right erector spinae muscles (P<=0.08). Pain played a significant role on the 10th, 50th and 90th percentile (P<0.05) of lateral flexion angle (side bending). The present study emphasizes biomechanical adaptations occurring in presence of neck-shoulder pain during cleaning tasks. PMID- 22316766 TI - Workers' postural conditions in the charcoal production proccess based on vertical metallic cylynders. AB - Considering the importance of posture to the workers' health in the production of charcoal, this paper presents an ergonomic research based on a biomechanical focus that aims to evaluate the posture adopted by these workers on the production of charcoal in vertical metallic cylinders. Thus, it was verified the incidence of pain and/or musculoskeletal injuries to these workers. Also, it was evaluated the weight carried by them and the positions taken in their daily tasks. Applying the Ergonomic Analysis of Labor, the data collection was done by directly observing the workers, registering images, by interviews, and posture analysis based on the OWAS method. The main results of the research show that there are postures with risks in the four levels of musculoskeletal injuries classified by OWAS, concluding that the method is imperative for ergonomic recommendations for minimization or eradication of suffering injury and worker's postural constraints. PMID- 22316767 TI - Heavy physical work under time pressure: the garbage collection service--a case study. AB - The increased generation of garbage has become a problem in large cities, with greater demand for collection services. The collector is subjected to high workload. This study describes the work in garbage collection service, highlighting the requirements of time, resulting in physical and psychosocial demands to collectors. Ergonomic Work Analysis (EWA) - a method focused on the study of work in real situations was used. Initially, technical visits, global observations and unstructured interviews with different subjects of a garbage collection company were conducted. The following step of the systematic observations was accompanied by interviews conducted during the execution of tasks, inquiring about the actions taken, and also interviews about the actions, but conducted after the development of the tasks, photographic records and audiovisual recordings, of workers from two garbage collection teams. Contradictions between the prescribed work and activities (actual work) were identified, as well as the variability present in this process, and strategies adopted by these workers to regulate the workload. It was concluded that the insufficiency of means and the organizational structure of management ensue a situation where the collection process is maintained at the expense of hyper requesting these workers, both physically and psychosocially. PMID- 22316768 TI - Evaluation of thermal overload in boiler operators. AB - The Brazilians educational institutions need a large energy demand for the operation of laundries, restaurants and accommodation of students. Much of that energy comes from steam generated in boilers with wood fuel. The laboral activity in boiler may present problems for the operator's health due to exposure to excessive heat, and its operation has a high degree of risk. This paper describes an analysis made the conditions of thermal environment in the operation of a B category boiler, located at a Higher Education Institution, located in the Zona da Mata Mineira The equipments used to collect data were Meter WBGT of the Heat Index; Meter of Wet Bulb Index and Globe Thermometer (WBGT); Politeste Instruments, an anemometer and an Infrared Thermometer. By the application of questionnaires, the second phase consisted of collecting data on environmental factors (temperature natural environment, globe temperature, relative humidity and air velocity). The study concluded that during the period evaluated, the activity had thermal overload. PMID- 22316769 TI - Is there enough information to calculate the financial benefits of ergonomics projects? AB - Many authors studied work situations and, mainly, ergonomics projects concerning the financial benefit point of view. At the same time seems to be little information available concerning these financial benefits in manufacturing companies' processes. The aim of this article is to identify if there enough information available within a company to quantify the financial benefits of an ergonomic project. The study was applied on two manufacturing companies, one in Brazil and other in Portugal. A literature review based checklist and a manager interview was applied on each company in order to identify if the information was available and how were been used. The two companies have revealed a good quantity of available information regarding ergonomics benefit calculation. The interviews showed that managers are not aware of the financial savings possibility with investments in ergonomics projects. PMID- 22316770 TI - Evaluating the effectiveness of ergonomics application. AB - The effectiveness of ergonomics application is achieved in the course of this research by reviewing ergonomics literature, Internet searches and case studies of a number of work related musculoskeletal disorders (WMSD's) and other ergonomic related workplace incidence rate. The results of ergonomic intervention control measures such as engineering controls, administrative controls and personnel protective equipment were also studied. The findings in this paper may help to development model for analysing and solving ergonomic problems in the workplace. It concludes on the need for management to support ergonomics intervention programme for effective cost saving, litigation avoidance and better productivity. PMID- 22316771 TI - Evidence-based ergonomics: a model and conceptual structure proposal. AB - In Human Factors and Ergonomics Science (HFES), it is difficult to identify what is the best approach to tackle the workplace and systems design problems which needs to be solved, and it has been also advocated as transdisciplinary and multidisciplinary the issue of "How to solve the human factors and ergonomics problems that are identified?". The proposition on this study is to combine the theoretical approach for Sustainability Science, the Taxonomy of the Human Factors and Ergonomics (HFE) discipline and the framework for Evidence-Based Medicine in an attempt to be applied in Human Factors and Ergonomics. Applications of ontologies are known in the field of medical research and computer science. By scrutinizing the key requirements for the HFES structuring of knowledge, it was designed a reference model, First, it was identified the important requirements for HFES Concept structuring, as regarded by Meister. Second, it was developed an evidence-based ergonomics framework as a reference model composed of six levels based on these requirements. Third, it was devised a mapping tool using linguistic resources to translate human work, systems environment and the complexities inherent to their hierarchical relationships to support future development at Level 2 of the reference model and for meeting the two major challenges for HFES, namely, identifying what problems should be addressed in HFE as an Autonomous Science itself and proposing solutions by integrating concepts and methods applied in HFES for those problems. PMID- 22316772 TI - Ergonomic evaluation of a situation of coexposure to solvents and noise in a printing of flexible packaging. AB - The purpose of this paper is to present an ergonomic evaluation of a situation of co-exposure to solvents and noise in a flexible packaging printer. We discuss how such an approach carried out in the field of printing industry work has made it possible to highlight serious shortcomings in the effectiveness of the prevention actions that are supposed to protect workers from chemicals risks and noise. The ergonomic analysis identified a strain working conditions. Indeed, some jobs expose to noise and toxic risk. Lamination operations, winding and cutting are purveyors of noise. Some physical and spatial factors contribute to amplify the toxic risk. The not wearing of personal protective equipment (PPE) by the operators maybe explained by the fact that it doesn't any possibility to do "otherwise". Indeed, operators adopt a compromise to achieve the objectives of production to the detriment of their health and safety. These constraints are causing gene and psychosocial factors. The interviews revealed a state of psychosis in the workshop, which was accentuated by the reclassification of an operator which has created a climate of panic and anxiety especially for older operators who have more than 20 years exposed to handling of toxic and more exposure to high noise level. PMID- 22316773 TI - The utilization of infrared imaging for occupational disease study in industrial work. AB - Infrared imaging has been used to visualize superficial temperatures in industrial employers standing and working in an indoor environment at 22 degrees C. Temperature distributions and changes have been recorded digitally and analyzed. Mean skin temperatures determined by this method have been compared with superficial temperatures obtained with a probe thermocouple. During working hours, surface temperatures were higher over extensor muscles than over other structures and their spatial distributions differed dramatically from those observed before working hours. The authors also analyzed the cold water immersion of the hands during work. This paper showed that working generates different thermal effects on human skin that reflect physiological and pathological occupational conditions and can be monitored by infrared imaging. PMID- 22316774 TI - Three years of the OCRA methodology in Brazil: critical analysis and results. AB - The Authors make a detailed analysis of the introduction of the OCRA Methodology in Brazil that started in August 2008 with the launching of the "OCRA Book" translated to Portuguese. They evaluate the importance of the assessment of the exposure of the upper limbs to the risk due to repetitive movements and efforts, according to the national and international legislation, demonstrating the interconnection of the OCRA Methodology with the Regulating Norms of the Ministry of Labor and Work (NRs - MTE), especially with the NR-17 and its Application Manual. They discuss the new paradigms of the OCRA Method in relation to the classic paradigms of the ergonomic knowledge. They indicate the OCRA Method as the tool to be used for the confirmation or not of the New Previdentiary Epidemiologic Nexus NTEP/FAP. The Authors present their conclusions based on the practical results the "participants certified by the OCRA Methodology" achieved in the application on different laboral activities in diverse economic segments, showing the risk reduction and the productivity of the companies. PMID- 22316775 TI - Correlation of ergonomic risk factors with RULA in IT professionals from India. AB - Work-related musculoskeletal disorders (WMSD) are common in computer professionals worldwide. Studies have shown that there is an association between the working posture and the development of musculoskeletal disorders. The IT professionals are exposed to different awkward posture while working. Therefore, it is expected that workers may develop different kinds of musculoskeletal discomfort/pain. This study aimed at to find out the relationship between the musculoskeletal discomfort and the postural score. RULA was used for postural analysis. Results of the postural analysis revealed that 30% of the participant's posture need to "modify soon" and 15% need to modify "immediately". 78% of the participants were using computer for more than 8 hours in a day. The major workstation risk factors were reported as improper keyboard height and mouse tray height (32%), improper monitor height (27%) and improper chair height (12%). Results also revealed a significant association between the regional body pain and the RULA score. Musculoskeletal pain was significantly associated with workstation keyboard/mouse surface (r=0.55) and duration of computer use (r=0.64). Intervention programme was recommended for the participant to modify the workstation and the working posture. PMID- 22316776 TI - Remote online ergonomic assessment in the office environment as compared to face to-face ergonomic assessment. AB - GOAL: remote online ergonomic assessment in the office environment as compared to face-to-face ergonomic assessment and examination of the applicability of remote online ergonomic assessment to office workers. 40 employees from a large Israeli hi-tech company were ergonomically assessed per the University of California computer usage checklist, according to the two assessment types (face-to-face and remote). An additional Ergonomist "assessor 2" examined the credibility of the process. RESULTS: Research hypothesis 1 was verified: 21 out of 22 questions (95.45%) from the checklist indicated compatibility between "assessor 1" to the "Gold Standard" at an 80% level. Research hypothesis 2: examining the credibility between the assessors with regard to remote assessment. This hypothesis was partially verified, the correlation between the assessors was measured at 0.54. Research hypothesis 3: examining the extent of deviation of natural posture between distal body parts assessment (distant from the center of the body) and proximal body parts (close to the center of the body). This hypothesis was clearly verified. It has been proven that there is statistical significance between the results. CONCLUSIONS: The current research has proved that there is an additional method to assess musculoskeletal disorders risk factors remotely online at office environment. PMID- 22316777 TI - Performance indicators of work activity. AB - The measurement of performance is a current topic in the management of people in companies, used as a parameter of effectiveness of processes and operations of production. The methods and models of the indicators of current use in the production have concentrated in the assessment of people's performance as determinative resource of the organizational success in the search for the competitiveness. Associated with the classic indicators of performance assessment of the production proceeding, other indicators are used in the assessment of risks and hazards, however with methods focused in the tasks, without connection with the real work activity. The present article explores literature on the models of performance measurement in use in companies and a field research to understand how companies interpret and use indicators that relate health and work, to direct future studies on the subject. Regarding the literature review, one can see that health indicators can be basically divided into two major groups: the legal and managerial indicators. When conducting case studies, it can be realized that companies do not have precisely the concept of health indicator, or were unable to define which of the indicators could be considered indicators of health, considering that absenteeism was the indicator mentioned by the four companies. PMID- 22316778 TI - Evaluation and control of ergonomics actions in federal public service: the case of FIOCRUZ-RJ. AB - This article presents information about the development of the dissertation. Deals with the production of ergonomic diagnosis in the environments and work processes of an important center of research and development in Public Health, FIOCRUZ. Critically evaluates the performance of a team promoting and facilitating the process of implementing ergonomic changes suggested. Through analysis of documents and statements by some managers and representatives of Human Resources was possible to identify the factors that facilitate and hinder the implementation process, linking them to the organization of the institution and conduct of the agents involved. Finally, it makes a reflection on practice, results and developments involved in the processes of change initiated by the ergonomic actions, proposing its replication along with other institutes of the Civilian Personnel of Federal Public Administration. PMID- 22316779 TI - Analysing domestic activity to reduce household energy consumption. AB - This paper presents our reflections on the issue of behavioral change according to energy conservation constraints and on the status of sustainability in the design of ambient interactive systems at home. We point out how ergonomics contributes to the study of human factors underlying energy consumption. Relating to situated cognition and human computer interaction, our approach relies both on the ergonomic evaluation of feedback consumption displays and on the modeling of domestic activities in order to identify household concerns in real settings. We present empirical results to illustrate this global approach. The results of those studies allow the design of interactive systems: informative and pedagogical systems as well as pervasive and adaptive ambient systems. In our approach, sustainability is taken into account as a design criterion, as security could be, whereas the main design purpose is to aid households in their daily life in order to build a "sustainable situation". PMID- 22316780 TI - Ergonomic analysis jobs in recovered factories. AB - With the advent of the deep economic crisis in Argentina on 2001, the recovery of companies through to the creation of the Cooperatives Working Self-Management or Factories Recovered by its workers was constituted as one of the ways in which the salaried disobeyed the increasing unemployment. When the companies turn into recovered factories they tend to leave of side practices that have been seen like imposed by the previous organization and not understanding them as a primary condition for the execution of his tasks. Safety and ergonomics are two disciplines that are no longer considered relevant to the daily work. Therefore this investigation aims to revalue, undergo semantic to give back to a place in every organization analyzed. This research developed a self-diagnostic tool for working conditions, and the environment, present in the recovered factories. PMID- 22316781 TI - From ergonomics to design specifications: contributions to the design of a processing machine in a tire company. AB - The development of ergonomics' recommendations, guidelines and standards are attempts to promote the integration of ergonomics into industrial contexts. Such developments result from several sources and professionals and represent the effort that has been done to develop healthier and safer work environments. However, the availability of large amount of data and documents regarding ergonomics does not guarantee their applicability. The main goal of this paper is to use a specific case to demonstrate how ergonomics criteria were developed in order to contribute to the design of workplaces. Based on the obtained results from research undertaken in a tire company, it was observed that the ergonomics criteria should be presented as design specifications in order to be used by engineers and designers. In conclusion, it is observed that the multiple constraint environment impeded the appliance of the ergonomics criteria. It was also observed that the knowledge on technical design and the acquaintance with ergonomic standards, the level of integration in the design team, and the ability to communicate with workers and other technical staff have paramount importance in integrating ergonomics criteria into the design process. PMID- 22316782 TI - Assesment of managerial behavior in the correction of ergonomic problems at an airport. AB - As demanded at Collective Employment Agreement (CEA), three ergonomic assessment of work (AEW) were made into an airport from a big Brazilian city (in particular, at the flight tower), with a 2 years interval between them. The objective was to produce a report pointing out problems and solutions. At the third time (2010), were verified that the work conditions where almost the same from 2006 and 2008, although all recommendations made in the reports. This work presents how the AET Team worked with this situation. At the third AEW, due the lack of real changes and the necessity of a report, the strategy was to know how workers where dealing with the complains and constraint detected at the previous reports, and how it interfere in abnormal or danger situations. Trying to explain this organizational phenomenon, we resort to Resilience Engineering to understand how those f/actors played to achieve its objectives. PMID- 22316783 TI - Ergonomic considerations for a systemic approach: the millenium maize mills project in northern Mozambique. AB - Malnutrition is a major problem for rural areas of Sub-Saharan Africa. Technology such as the maize mill, which alleviates the burden of pounding grain, also introduces opportunities and new challenges for improved nutrition. While there have been many technical studies of grain mills, and maize mills are in operation in hundreds of locations throughout Sub-Saharan Africa, the maize mill has not been studied from a socio-technical system perspective. This paper reports on the first phase of a study grounded on the hypothesis that mills can improve nutrition by exploiting their function as a social gathering point and providing both instruction and enjoyable healthful products. The objective was to identify those products that could be made available that customers at the mill would be willing to buy. Following observation of food availability, preparation, and consumption preferences within daily work routines, sample products were prepared and presented for cooking and consumption, along with some discussion at a district center mill owned by a local woman. The responses of customers and the mill owner were positive. Strategies for local manufacture and distribution of these products for sale and roles of the mill owner and the mothers are questions for future study. PMID- 22316784 TI - Forensics ergonomics in Spain. Research priorities by the Delphi technique. AB - Among the many fields of application of Ergonomics, this research deals with the services offered to Justice from the expertise recognized by the Law on prevention of occupational risks within the framework of the Law of Civil Procedure: Ergonomics forensic also called Legal Ergonomics. In Spain there are experiences since 1995 and an important development and this paper is to investigate the actions required for a more widespread use in trials. Consensus methods such as the Delphi survey technique are being employed to help enhance effective decision-making in the future development of Ergonomics Forensics. The Delphi survey is a group facilitation technique, which is an iterative multistage process, designed to transform opinion into group consensus. It is a flexible approach, that is used commonly within the health and social sciences, however, there is little use and practice of ergonomics as a technique to facilitate the participation of all experts involved: judges, lawyers and expert ergonomists. PMID- 22316785 TI - Promoting ergonomics in Algeria: activities of "the research and training laboratory" in the University of Oran. AB - The growing need in Algeria to develop ergonomics knowledge and practice in industry was behind the initiative to develop a training and research project within the ergonomics laboratory at Oran University. Since 2005 the laboratory team is running an academic option master in work design and ergonomics. The evaluation of the academic master in 2010 revealed the acute need of the local industry for professional competences in ergonomic and work psychology. A professional training master program in "ergonomics & work psychology" was then developed in partnership with local industry, five European Universities and six Universities from three Maghreb countries. Research projects were initiated around the two training programs, in conjunction with a number of ergonomics dissemination and promotion activities. Preliminary results of the project are presented and discussed in relation to the local context, and in the light of similar cases in Industrially Developing Countries. PMID- 22316786 TI - Training in manual material handling: what is going on in the field? AB - During the last five years, several research review studies have revealed insufficient or even no proof that courses in manual material handling (MMH) are effective at preventing musculoskeletal disorders (MSD). These revelations are placing the current daily practice of MMH trainers under scrutiny. This study analyses how the MMH courses are organised in practice. A web-based questionnaire was developed for trainers. Only trainers giving MMH courses on a regular basis were included. The questionnaire focussed on general characteristics of the courses, content issues and organisational aspects. The results clearly indicated that the MMH courses can only be considered as a means of making employees aware of good manual handling. Not all content issues that should be addressed in effective MMH courses, are looked at in practice. This is mainly due to time restrictions that trainers experience, often imposed by the company. In conclusion, these organisational restrictions might explain the ineffectiveness of the MMH courses and should therefore be resolved. PMID- 22316787 TI - Ergonomic assessment methodologies in manual handling of loads--opportunities in organizations. AB - The present study was developed based on the analysis of workplaces in the engineering industry, particularly in automotive companies. The main objectives of the study were to evaluate the activities present in the workplace concerning manual handling, using assessment methodologies NIOSH Ergonomic Equation [1] and Manual Material Handling [2], present in ISO 11228 [3-4], and to consider the possibility of developing musculoskeletal injuries associated with these activities, an issue of great concern in all industrial sectors. Similarly, it was also shown the suitability of each method to the task concerned. The study was conducted in three steps. The first step was to collect images and information about the target tasks. As a second step proceeded to the analysis, determining the method to use and to evaluate activities. Finally, we found the results obtained and acted on accordingly. With the study observed situations considered urgent action, according to the methodologies used, and proceeded to develop solutions in order to solve the problems identified, eliminating and / or minimizing embarrassing situations and harmful to employees. PMID- 22316788 TI - The manual transport of load and the commercial aviation in Brazil. AB - The Brazilian commercial aviation industry has grown strongly in the last decades, increasing passenger capacity and operational safety. While several studies focus on flight safety and passenger comfort, few are dedicated to the manual transport of loads. Although apparently this sector has low relevance, every year nearly 9% of their workers are injured. It is estimated that these injuries cost more than 10 million dollars a year to the companies involved. This study assesses quantitatively the risk of injury on employees. NIOSH method was used to evaluated the possibility of injury in different tasks. Factors such as the pace of activity, horizontal and vertical displacement, and asymmetries were evaluated during loading and unloading of luggage. This study showed that the frequency of repetitions of loading was excessive in all cases analyzed. However, the use of conveyors reduced the risk of employee injury, reducing this possibility to acceptable levels. The study shows that simple measures can help reduce the number of injuries and hence the cost that this entails. PMID- 22316789 TI - Quantification of hand grasp force using a pressure mapping system. AB - The goal of this study was to use a pressure sensor to measure the force distribution and contact area of the hand when gripping, pushing, and pulling a cylinder. Data was collected from 10 subjects with no hand impairments and from 1 subject with rheumatoid arthritis (RA). Subjects grasped an aluminum cylinder wrapped with a Tekscan pressure sensor and performed each trial at 25%, 50%, and 100% maximum voluntary exertion. A relationship was found between increasing exertion and increasing hand area with increasing hand contact area. The force distribution maps showed the thenar region of the hand exerts the most force during pushing while the metacarpal joint line exerts the highest force during pulling. The third and fourth phalange were found to exert the highest phalange force during gripping. The force distribution maps from the RA subject showed higher thumb forces and distal phalange forces, relative to the entire phalange, compared to the non-impaired subjects. This suggests that the RA subject compensates for the lack of phalange function with the regions of the hand that still function. Future studies should sample individuals with a larger hand area range and sample more individuals with RA. PMID- 22316790 TI - Human activity reference database. AB - The first sentence of the Abstract should follow the word "Abstract." on the same line. The abstract should be clear, descriptive, self-explanatory and no longer than 200 words. It should also be suitable for publication in abstracting services. Do not include references or formulae in the abstract. PMID- 22316791 TI - Cognitive chrono-ethnography lite. AB - Conducting field research facilitates understanding human daily activities. Cognitive Chrono-Ethnography (CCE) is a study methodology used to understand how people select actions in daily life by conducting ethnographical field research. CCE consists of measuring monitors' daily activities in a specified field and in depth interviews using the recorded videos afterward. However, privacy issues may arise when conducting standard CCE with video recordings in a daily field. To resolve these issues, we developed a new study methodology, CCE Lite. To replace video recordings, we created pseudo-first-personview (PFPV) movies using a computer-graphic technique. The PFPV movies were used to remind the monitors of their activities. These movies replicated monitors' activities (e.g., locomotion and change in physical direction), with no human images and voices. We applied CCE Lite in a case study that involved female employees of hotels at a spa resort. In-depth interviews while showing the PFPV movies determined service schema of the employees (i.e., hospitality). Results indicated that using PFPV movies helped the employees to remember and reconstruct the situation of recorded activities. PMID- 22316792 TI - Ergonomics principles to design clothing work for electrical workers in Colombia. AB - The recent development of the Colombian legislation, have been identified the need to develop protective clothing to work according to specifications from the work done and in compliance with international standards. These involve the development and design of new strategies and measures for work clothing design. In this study we analyzes the activities of the workers in the electrical sector, the method analyzes the risks activity data in various activities, that activities include power generation plants, local facilities, industrial facilities and maintenance of urban and rural networks. The analyses method is focused on ergonomic approach, risk analysis is done, we evaluate the role of security expert and we use a design algorithm developed for this purpose. The result of this study is the identification of constraints and variables that contribute to the development of a model of analysis that leads to the development the work protective clothes. PMID- 22316793 TI - The construction of ergonomic demands: application on artisan fishing using jangada fishing rafts in the beach of Ponta Negra. AB - The present article seeks the process of construction of ergonomics demand referring to the artisan fishing activityfound in Ponta Negra beach located in the city of Natal, Brazil. The instruction/construction of demands correspond to the first stage of Work Ergonomic Analysis and allows the understanding of real issues existent in a work situation, rank them and route the providences. The demand presented on this study, features itself as a induced demand, process which some potential demands or hypothetical demands are taken to an organization, after a preview analysis of the work aimed by the study, resulting from a theoretical research (state of the art) and/or from analysis of a reference situation (state of practice), where demands hypothesis are taken in consideration about the pretended work. The demands construction process using interactional methods and techniques, observation methods and techniques and bibliographic research, researches in state of reference or document. This article demonstrates the efficiency of the methodological choice to construct real ergonomic demands and highlights the importance of social construction on that process, which main goal is to refer the ergonomic actions that allow the improvement of work and life conditions for the fishers and sustainability to Jangadeira activity. PMID- 22316794 TI - Ergonomic tridimensional analysis: critical ergonomic factors identification in a commercial environmental. AB - The Ergonomic tridimensional analysis (ETdA) was developed to be used as an auxiliary tool on the ergonomic intervention. It was specially designed for commercial areas with free circulation of people. Due to that, the client, the third ETdA dimension, becomes an important element and their opinions relevant in the ergonomic analysis. The remains two ETdA dimensions, professionals and analyst, play an identical role as in the traditional occupational ergonomic analysis. For each of these dimensions, specific observation tools were assembled: an ETdA questionnaire, an evaluation form and a checklist for direct and indirect observations. The variables that allow the ETdA operability are identified as Ergonomic Factors (EFs). A case study is presented identifying, for each dimension, the critical EFs. This will allow the design of the weighting table, where the influence of each dimensions results is measured, stressing the important role of clients on ergonomic issues. PMID- 22316795 TI - Science as a service: understanding successful knowledge transfer in a New Zealand research institute. AB - This paper reports on an exercise conducted within a state-owned body (Crown Research Institute) in New Zealand aimed at building greater understanding of the key factors in successful research programmes. Success was defined in this study as a high level of uptake of the emerging science, with commensurate benefits to both industry and the community. The methodology had three parts. A review of the knowledge and technology transfer literature; a series of 15 semi-structured interviews with science leaders; and a facilitated workshop. The purpose of the review was to generate a robust framework upon which to centre the interview dialogues, and two models were selected. The results varied, reflecting the diversity of research services provided by the organization, but the findings were predominantly new and valuable. The importance of the long term relationship with the end users was the strongest recurring theme. The methodology may have wider application in both research and consulting settings; for the benefits derived from the interactive process with staff, as well as for the specific findings. PMID- 22316796 TI - Ergonomics and environmental sustainability: a case study of raft fisherman activity at Ponta Negra Beach, Natal-RN. AB - This paper aims to present the significance of methods used by the Ergonomic Analysis of Work for the construction of the scenario of craft fishing with rafts, held by 42 fishermen on the beach of Ponta Negra, Natal - RN; and relate the knowledge in ergonomics to environmental aspects / impacts, aiming the sustainability in this activity. This research is characterized as a case study, of the descriptive and exploratory type and of applied nature. To collect data, we used observational methods, in order to expand information about the activity, and interaction, as conversational action and photographic/videos records to clarify points not covered by observation. It was observed problematic as the reduction of fishing productivity, alterations of the sea, difficulty in docking the rafts, and inadequate waste disposal, noting that this activity needs care regarding the use of the environment. The obtained results contributed to the organization of environmental education workshops, seeking to enhance good individual / collective environmental practices focused on the sustainability of the environment in which they live. Add the need for proposals aimed for managing the activity, involving fishermen, institutions and society, to ensure the improvement of the environment, hence the quality of life of the population. PMID- 22316797 TI - Maintenance of submersible pumps in the septic tanks: ergonomic and biological risks to the worker. AB - In this study was observed the maintenance task of submersible pumps septic tanks installed in industrial bathrooms. This maintenance activity operators are exposed to various biological and ergonomic risks. This type of activity requires its great physical performers who are also subject to contact with human waste in the form of liquids, gases and solids. Besides the problems mentioned, are still exposed to high temperatures that can cause diseases such as hyperthermia or heatstroke. These aspects were observed using the ergonomic assessment methodology in order to suggest improvements that are reflected in productivity and employee satisfaction. PMID- 22316798 TI - Development of an instrument for assessing workstyle in checkout cashier work (BAsIK). AB - Checkout cashier work consists of handling a large number of items during a work shift, which implies repetitive movements of the shoulders, arms and hands/wrists, and a high work rate. The work is associated with a high prevalence of disorders in the neck and upper extremity. The concept of workstyle explains how ergonomic and psychosocial factors interact in the development of work related upper extremity disorders. The aim of the project was to develop an instrument for the occupational health services to be used in the efforts to prevent upper extremity disorders in checkout cashier work. The instrument is based on the workstyle concept and is intended to be used as a tool to identify high-risk workstyle and needs for interventions, such as training and education. The instrument, BAsIK, consists of four parts; a questionnaire about workstyle, an observation protocol for work technique, a checklist about the design of the checkout and a questionnaire about work organization. The instrument was developed by selecting workstyle items developed for office work and adapting them to checkout cashier work, discussions with researchers and ergonomists, focus-group interviews with cashiers, observations of video recordings of cashiers, and studies of existing guidelines and checklists. PMID- 22316799 TI - Multi dimensional system for evaluating preventive program for upper extremity disorders among computer operators. AB - Typing is associated with musculoskeletal complaints (MSCs), caused by multiple risk factors. Although a wide variety of ergonomic intervention programs were conducted to reduce risk factors and MSC's, only few of them were found evidence based. This study aimed to test the efficacy of a workplace intervention in reducing MSC's among computer workers. 66 computer workers were assigned randomly to one of three intervention programs: ergonomic intervention including biofeedback, intervention without biofeedback and control group without intervention. The efficacy was tested by advanced assessment including; pain location and severity, posture at work, upper extremity 3D kinematics, muscle activity and psychosocial status. Working hypothesis; significant score differences will be found between the study groups which underwent ergonomic intervention and the control group on the following measures: pain complaints, upper extremity kinematics, muscle activity and psychosocial status. Significant differences were found between pre and post intervention and between research groups and the control group in pain, posture and motion. The ergonomic intervention with biofeedback had no unique contribution in comparison to other interventions. In conclusion; the proposed intervention program was found efficient for reducing pain among computer workers. PMID- 22316800 TI - Support of the upper limbs of office workers during a daily work journey. AB - Generally, the studies assess the upper limbs postures during the work with Visual Display Terminal - VDT through the measurement of the angles formed by the segments or through the relation with the pre-defined anatomical postures (e.g., flexion, extension, abduction). However, few studies were found in the literature which had focused in the measurement of the upper limbs support during a real situation of work with VDT and in the definition of analysis categories for this kind of behavior. The main objective of this study was to measure, in a real situation and using a systematic observation method through video analysis, the main kinds of support for the upper limbs. The analysis was done considering 480 work hours of 30 office workers. Data were collected using a methodology proposed by Rebelo, Filgueiras & Soares [1] and related with the work organization and workspace conditions, the participants had: a) minimum of eight hours daily of work; b) similar activities, characterized as office work; c) same furniture and equipment; and, d) computers with the same hardware, software and peripherals. Results were analyzed 46554 dynamic events, considering only the fourteen Interaction Categories - ICs, for upper limps support. In this way, percentage was computed, considering the total number of occurrence, for the Right arm is: arm support (0.06%); forearm support (31,8%); elbow support (31,92%); hand support (7,41%); multiple supports (12,32%) and without support 16,41%- For the Left arm the results is: forearm support (0,11%); arm support (53,69%); elbow support (8,70%); hand support (7,97%); multiple supports (8,43%) e without support (21,11%). This systemic and ecological approach was obtained through a method which enables experimental Biomechanics and Physiology methods to develop more efficient functional requirements and recommendations for the work with VDTs. PMID- 22316801 TI - Situated modelling in the drawing workshop for bobbin lace. AB - The current article presents the process of situated modeling in the drawing workshop for bobbin lace developed and implemented in the Nucleo de Producao Artesanal Rendeiras da Vila, in Ponta Negra, Natal-Brasil. The workshop aimed to rescue the domain over the product in the production of bobbin lace through capacitation of both experienced and novice craftswomen. The modeling of the drawing workshop was grounded on the sociotechnical construction and in the concepts of anthropotechnology and also social technology. The modelling required an intense process of social construction involving the members of GREPE-UFRN (Group of extension and Research in Ergonomics) and the lacemakers od the community. The domain of drawing the lace has enabled the expression of the craftswomen creativity, increasing the amount of works and the sustainable development,thus reducing the risks of extinction of such art in the Village of Ponta Negra. PMID- 22316802 TI - Ergonomics work analysis applied to dentistry--a Brazilian case study. AB - This paper presents the Ergonomic Work Analysis method in a Brazilian Dentist's office. Through the study, the constraints and the strategies in avoiding them were identified. It was found that dentists hardly use the position most indicated by the International Organization for Standardization (ISO) and the Federation Dentaire Internacionale (FDI) for both the patient and the dentist, which is respectively supine and 9 o'clock, due to the limited space and layout. Five types of treatments performed by the professional have been studied. The frequency and duration of actions in these treatments were accounted for and the standard positions adopted were identified. The AET was found to be a very suitable method to grasp the dentist's activity and build a point of view of the profession, which is characterized as: stressful, perfectionist and restrictive. Time management is presented as an important strategy to control the tension arising from performing the treatments. PMID- 22316803 TI - The overload at work and outside of work: the case of woman operators of blistering. AB - The internationalization of labor is a prominent feature of the economy today, but is accompanied by adverse effects on operator health. In general, musculoskeletal diseases are the first to appear in this context. The open observations activity and interviews with operators and the hierarchy have been made to discover the organizational constraints. Other interviews were also conducted to account for the determinants of activity outside of work. The use of video has allowed the registration of work cycles, which helped to describe and quantify the postures and gestures to establish a possible link between musculoskeletal diseases and work activity. The collected data were processed using software Actogram Kronos. To understand the process of origin of these diseases, the analysis of the socioeconomic context is also essential because they in part determine the organization of certain companies. The objective of this paper was to discuss the activities of operators of blistering in both work and outside work. The goal is to determine the constraints presents in these two spheres of activity, that may increase the risk of developing musculoskeletal diseases and to define their interaction. PMID- 22316804 TI - Ergonomics analysis of the activity of boning shoulder in a pig slaughter-house in the city of Ipiranga-SC. AB - The incidence of workers suffering from occupational injuries has alerted health professionals and entrepreneurs. Enterprises are looking for improvements in production systems by investments in quality, technological innovations and in human resources that are capable and committed to the objectives and targets of the enterprise. This research was developed in a pig slaughter-house in the city of Ipiranga-SC, in the labor of boning shoulder of the pig, because this is the activity that presents more registers of complaints of pain and also probability of development of occupational diseases with cause in the enterprise.Tools of Ergonomics Analysis of Work were used, from interviews with workers to the application of LEST method in the activity analyzed. The necessity of immediate intervention in the work station was shown in the results, because of the high risk of prejudice to the health of the workers. Improvement actions must be done to satisfy the ergonomics requirements of NR 17 standard, attending the enterprise interests in the occupational diseases prevention. PMID- 22316805 TI - Ergonomic evaluation in a values transportation company in Venezuela. AB - The objective was to analyze the work activity and identify risk factors that could account for musculoskeletal disorders in the upper extremities, shoulder and neck of workers of a transport values company in Venezuela. The methods used were: collective interview, tasks observation, evaluation of posture with RULA method and evaluation of repetitive motions with the OCRA method. Five workstations were evaluated. Main problem perceived by workers was: exposure to chemical and biological hazards when handling paper money and coins; inadequate chairs and close supervision. The postures level risk was 1 or 2 for the RULA scale. Only two workstations showed ligth and medium risk level by OCRA method. CONCLUSION: The factors identified that could explain the musculoskeletal changes were: wrist repetitive flexion and extension, shoulder elevation, lifting weight above shoulder height, elbow repetitive flexion and extension, neck flexion, extended work journey, work overload, high responsibility and strict supervision by a video camera. PMID- 22316806 TI - Investigation of the impact of main control room digitalization on operators cognitive reliability in nuclear power plants. AB - Currently, there is a trend in nuclear power plants (NPPs) toward introducing digital and computer technologies into main control rooms (MCRs). Safe generation of electric power in NPPs requires reliable performance of cognitive tasks such as fault detection, diagnosis, and response planning. The digitalization of MCRs has dramatically changed the whole operating environment, and the ways operators interact with the plant systems. If the design and implementation of the digital technology is incompatible with operators' cognitive characteristics, it may have negative effects on operators' cognitive reliability. Firstly, on the basis of three essential prerequisites for successful cognitive tasks, a causal model is constructed to reveal the typical human performance issues arising from digitalization. The cognitive mechanisms which they impact cognitive reliability are analyzed in detail. Then, Bayesian inference is used to quantify and prioritize the influences of these factors. It suggests that interface management and unbalanced workload distribution have more significant impacts on operators' cognitive reliability. PMID- 22316807 TI - Competing values, tensions and trade-offs in management of nuclear power plants. AB - The specific goal of the study is to look how tensions, competing values and trade-offs manifest in the management of nuclear power plants. Second goal is to inspect how existing frameworks, such as Competing Values Framework, can be used to model the tensions. Empirical data consists of thirty interviews that were conducted as part of a NKS study on safety culture in the Nordic nuclear branch. Eight trade-offs are identified based on a grounded theory based analysis of the interview data. The competing values and potential tensions involved in the trade offs are discussed. PMID- 22316808 TI - The contribution of ergonomics to risk analysis in the design process: the case of a future control room. AB - The aim of this paper is to highlight how ergonomics contributes to risk analysis and risk management in a design project for a new reactor, the French EPR (European Pressurized Reactor). An iterative ergonomics design process has been conducted over the last 10 years through a Human Factors Engineering program at the French energy company EDF. A parallel has been drawn between a risk management process and this ergonomics process based on International Organization for Standardization (ISO) publications such as ISO/IEC Guide 73, ISO Guide 51, etc. The contribution of ergonomics to risk analysis is illustrated by an example: the automatic diagnosis, which is a very important technical device for safety. Five main types of risk have been identified via ergonomic analyses during the different design stages. Counter-measures have been implemented and their efficacy tested within the scope of new campaigns to assess human factors. However, the management of risks in such a design project requires the participation both of the different design entities involved in the project and of other experts in aspects of risk management, such as human reliability. The organization of collaborative participation remains a challenge to be addressed. PMID- 22316809 TI - From needs to requirements for computer systems: the added value of ergonomics in needs analysis. AB - It is widely recognised that ergonomists must contribute during needs analysis. However, few studies have investigated the specific contributions of ergonomists at this stage of the design process. In this study, this contribution is studied through the requirement document produced by the design team. For each requirement, the source (i.e. who formulated the requirement), justification (why the requirement is needed), type (functional, interaction, operational, physical, organizational), and scope (entire system or part thereof) were analysed. Results indicate that the various actors are complementary and work collectively to define the various dimensions of the system. With end-users, the ergonomist worked on the global aspects of the system: function, conditions of use and organizational dimension. Alone, he defined the global interaction of the system. The various functions derived from the global function were defined in collaboration with engineers. However, while engineers contributed to defining how these functions would work, as well as their technical conditions of use, the ergonomist focused on their purpose, and, with end-users, on their organizational aspects. Finally, results suggest that neither the ergonomist's specific knowledge in ergonomics, nor work analysis were sufficient to derive his requirements; both are mandatory. PMID- 22316810 TI - New procedures of ergonomics design in a large oil company. AB - This study presents the challenge involved in the negotiation and construction of a standard process in a major petroleum company that has the purpose of guiding the implementation of ergonomic studies in the development of projects, systemising the implementation of ergonomics design. The standard was created by a multi-disciplinary working group consisting of specialists in ergonomics, who work in a number of different areas of the company. The objective was to guide "how to" undertake ergonomics in all projects, taking into consideration the development of the ergonomic appraisals of work. It also established that all the process, in each project phase, should be accompanied by a specialist in ergonomics. This process as an innovation in the conception of projects in this company, signals a change of culture, and, for this reason requires broad dissemination throughout the several company leadership levels, and training of professionals in projects of ergonomics design. An implementation plan was also prepared and approved by the corporate governance, complementing the proposed challenge. In this way, this major oil company will implement new procedures of ergonomics design to promote health, safety, and wellbeing of the workforce, besides improving the performance and reliability of its systems and processes. PMID- 22316811 TI - Human factors engineering in oil and gas--a review of industry guidance. AB - Oil and gas exploration and production activities are carried out in hazardous environments in many parts of the world. Recent events in the Gulf of Mexico highlight those risks and underline the importance of considering human factors during facility design. Ergonomic factors such as machinery design, facility and accommodation layout and the organization of work activities have been systematically considered over the past twenty years on a limited number of offshore facility design projects to a) minimize the occupational risks to personnel, b) support operations and maintenance tasks and c) improve personnel wellbeing. During this period, several regulators and industry bodies such as the American Bureau of Shipping (ABS), the American Society of Testing and Materials (ASTM), the UK's Health and Safety Executive (HSE), Oil and Gas Producers (OGP), and Norway's Petroleum Safety Authority (PSA) have developed specific HFE design standards and guidance documents for the application of Human Factors Engineering (HFE) to the design and operation of Oil and Gas projects. However, despite the existence of these guidance and recommended design practise documents, and documented proof of their value in enhancing crew safety and efficiency, HFE is still not well understood across the industry and application across projects is inconsistent. This paper summarizes the key Oil and Gas industry bodies' HFE guidance documents, identifies recurring themes and current trends in the use of these standards, provides examples of where and how these HFE standards have been used on past major offshore facility design projects, and suggests criteria for selecting the appropriate HFE strategy and tasks for future major oil and gas projects. It also provides a short history of the application of HFE to the offshore industry, beginning with the use of ASTM F 1166 to a major operator's Deepwater Gulf of Mexico facility in 1990 and the application of HFE to diverse world regions. This latter point highlights the need to consider user populations when selecting HFE design criteria, an aspect strongly emphasized in current industry guidance. PMID- 22316812 TI - Ergonomics in designing process: dialogue between designers, executors and users in the maintenance activity of radars in an oil refinery. AB - This paper aims to discuss the role of ergonomics in design process using the dialogue developed by designers, implementers and users in an oil refinery. It was possible to identify the need of minimizing the postural constraints, risk of accidents, mechanical shocks and to enlarge safety perception in the access and permanency of the users at the workspace. It has been determined and validated by workers and managers to implement different deadlines depending on programming, viability and execution time for the improvements proposed. In a long-term: it was proposed the substitution of the ladders with time planning according to the maintenance program of the tanks; in a short-time: it was suggested the expansion of the existing platforms, implementation of a walkway connection provided with guardrails between the upper access of the side ladder and the repositioning of radar set and aerial aiming at the usage by workers at the workstation of the new platform. It was also elaborated eight typologies of intervention, according to the request, type of tank, material stored, and its setting place. The design process arises from ergonomics workplace analysis that presents concepts for solutions which was a mediator tool to be settled between users and implementers. PMID- 22316813 TI - Analysis of the implementation of ergonomic design at the new units of an oil refinery. AB - Ergonomic design is the adaptation of working conditions to human limitations and skills in the physical design phase of a new installation, a new working system, or new products or tools. Based on this concept, the purpose of this work was to analyze the implementation of ergonomic design at the new industrial units of an oil refinery, using the method of Ergonomic Workplace Assessment. This study was conducted by a multidisciplinary team composed of operation, maintenance and industrial safety technicians, ergonomists, designers and engineers. The analysis involved 6 production units, 1 industrial wastewater treatment unit, and 3 utilities units, all in the design detailing phase, for which 455 ergonomic requirements were identified. An analysis and characterization of the requirements identified for 5 of the production units, involving a total of 246 items, indicated that 62% were related to difficult access and blockage operations, while 15% were related to difficulties in the circulation of employees inside the units. Based on these data, it was found that the ergonomic requirements identified in the design detailing phase of an industrial unit involve physical ergonomics, and that it is very difficult to identify requirements related to organizational or cognitive ergonomics. PMID- 22316814 TI - The emergency system for the town of Milano: evaluation of an help point. AB - The article presents a complex work of which the author has been asked by the Municipality of Milan an its Service Company (AEM, now A2A) to apply Ergonomics to evaluate a product designed for asking information and emergency, with particular attention to vulnerable city users. PMID- 22316815 TI - Assessment of work ability of health professionals in the mobile emergency unit. AB - Ergonomics is the study of a workplace and the worker. Its aim is to better adapt the workplace to man by preserving the body for short and long term work. This helps to adjust and improve functionality, thus preserving the body for short and long term work. It was through the observation of SAMU's (Mobile Emergency Unit) professional's helpers that the interest to evaluate these individuals arose. In addition, the aim of this research is to investigate the work ability of health professionals that work for SAMU/JP. The population was composed of 97 health professionals who currently work for SAMU/JP. A sociodemographic questionnaire was used as data collection instrument and it was validated by the index of the Work Ability (WAI). The research took place in 2010, in the headquarters of SAMU, in the city of Joao Pessoa, state of Paraiba - Brazil. The data analysis was carried out by simple descriptive statistics followed by comparison of the results with the pertinent literature. The quantity of daily sleeping hours, the levels of satisfaction in the job and the number of diagnosed diseases were among the most worrying factors. In spite of this, the health professionals obtained a work ability average considered to be "good". PMID- 22316816 TI - Taking care of you and care for others: an analysis of the activity of the work of technical and nursing assistants of a psychiatric institution for children and adolescents. AB - Our objective in this study, the analysis of potential fields of risk management in nursing work in psychiatric care to adolescents and children, while settings that go from the relationship between technical and organizational determinants of work activity and the skills of operators. It was established focus on the work process of the Technical and Nursing Assistants to seek for response elements in an attempt to understand the health-disease process experienced by these workers. It was used for analysis and data collection, through the method of Ergonomic Work Analysis (EWA), fifteen workers of nursing staff - T&NA, between effectives and contractors, and the strategies of action and regulation of these workers in relation to the interface that they deal with. The results show that the workers are exposed to all charges in an intense and specific way, causing physical and mental wear, as it approaches the psychological distress, exposure to the psychic pressure, not only through contact with the object of work, but the complexity of these relationships that are involved in nursing staff. PMID- 22316817 TI - Designing the safety of healthcare. Participation of ergonomics to the design of cooperative systems in radiotherapy. AB - This communication deals with the involvement of ergonomists in a research-action design process of a software platform in radiotherapy. The goal of the design project is to enhance patient safety by designing a workflow software that supports cooperation between professionals producing treatment in radiotherapy. The general framework of our approach is the ergonomics management of a design process, which is based in activity analysis and grounded in participatory design. Two fields are concerned by the present action: a design environment which is a participatory design process that involves software designers, caregivers as future users and ergonomists; and a reference real work setting in radiotherapy. Observations, semi-structured interviews and participatory workshops allow the characterization of activity in radiotherapy dealing with uses of cooperative tools, sources of variability and non-ruled strategies to manage the variability of the situations. This production of knowledge about work searches to enhance the articulation between technocentric and anthropocentric approaches, and helps in clarifying design requirements. An issue of this research-action is to develop a framework to define the parameters of the workflow tool, and the conditions of its deployment. PMID- 22316818 TI - Conceptual design pattern for ergonomic workplaces. AB - In this paper, we analyzed two laboratories of liquid chromatography (LC), separation technique of mixtures and identification of its components, in order to identify projectual gaps relating to the environment and the working station. The methodology used was the ergonomic analysis with interactional and participatory techniques applied during the activity performance. This work incorporated and adapted the concept developed by Alexander (1979)--pattern languages--passing from architectural projects to workstations project and physical arrangement of the work environment. The adaptation of the concept resulted in a list of recommendations, requirements and concepts that have brought design solutions for the problematic aspects observed in the ergonomic analysis. The employed methodology, strongly supported in ergonomics principles, and in interactional and participatory techniques, contributed to achieve our gold that is what we now call Conceptual Standards. The patterns go beyond of a usual model of book a of ergonomics specification, once incorporating the viewpoint of the end user, it is also a set of best project practices and of project management in conception ergonomics. PMID- 22316819 TI - Participatory ergonomics and design of technical assistance. AB - This work describes the experience of application of a procedural initiative, which aimed to identify and address technical assistance needs progressively in therapy and rehabilitation activities. The proposal theoretical axes are the basics of participatory ergonomics and interdisciplinary work, was raised with the intention of addressing important issues for the entire design process including: perception, attention, memory and human being comfort, and the interrelationships that create objects in the context in which they are used. This project was done in collaboration with leading institutes for the rehabilitation of Colombia: Cirec and Roosevelt, through two investigative stages: a first ethnographic stage, during which were observed one hundred forty four (144) procedures of rehabilitation and therapy to build a bank of assistive technology needs, justified on the project observation variables. And a second stage of action research in which they were designed elements that facilitate the implementation of rehabilitation procedures efficiently. Currently being developed experiential situations in different hospitals to examine the reliability of the proposed solutions. PMID- 22316820 TI - Effects of early support intervention on workplace ergonomics--a two-year followup study. AB - The purpose of the controlled longitudinal study was to determine the effect of a tailored early support intervention method on workers' workplace ergonomics. The main areas of the early support intervention were training, guidance and support for supervisors in finding weak signals of impaired ergonomics. Supervisors were also trained to bring up these weak signals in discussion with employees and to make necessary changes at the workplace. The data consisted of 301 intervention subjects and 235 control subjects working in the field of commerce. The questionnaires were carried out in 2008 and in 2010, and the response rates among both groups were 45%. We used multivariate repeated measures analysis of variance (MANOVA) to test the difference in the groups at two points of time. The main result was that in the areas of work environment, the interaction between group and time was statistically significant (p=0.0004). The work environment improved in the intervention group, but deteriorated in the control. Working methods improved due to the interventions, but physical load factors increased over time in both groups. According to the study, tailored early support intervention has a generally beneficial impact on workers' workplace ergonomics in the areas of work methods, work environment and accident factors. PMID- 22316821 TI - A multi-ontology view of ergonomics: applying the Cynefin Framework to improve theory and practice. AB - Ergonomics literature has often identified concerns about the difficulty of gaining support for ergonomics interventions. There appears to be a shift from the view that ergonomics issues can be made to be simple, towards a wider appreciation of the complexity of ergonomics problems in the real world. A framework from knowledge management--the Cynefin Framework--is recommended as providing a way of re-perceiving situations where ergonomics problems may be present or have already been identified. The framework uses multiple ontologies and indicates appropriate courses of investigation and action for each of four domains--the simple, the complex, the complicated and the chaotic. This paper presents evidence of the need for a multi-ontology approach and shows how the Cynefin Framework can be applied to ergonomics. PMID- 22316822 TI - How do people differentiate between jobs: and how do they define a good job? AB - Employed individuals from a range of jobs (n=18) were interviewed using a repertory grid technique, to explore the criteria they used to distinguish between different jobs. The concepts of 'a good job' and 'a job good for health' were also discussed. Interactions with others and the job itself were the most commonly used criteria and were also the most common features of a 'good job'. Pay and security were mentioned frequently but were less important when comparing jobs and when defining a 'good job'. Physical activity was rarely associated by interviewees with a 'good job' but was frequently associated with a 'job good for health'. A comprehensive definition of a 'good job' needs to take all these factors into account. PMID- 22316823 TI - Usability testing with children: an application of Pedactice and Ticese methods. AB - Graphic representation of clickable areas in computer interfaces should allow mental representations that facilitate systems navigation during the cognitive process. If it doesn't happen users can feel lost. When thinking about websites designed to children with both entertainment and educational intention these systems must stimulates this kind of users. As many other activities for children nowadays, many system are commonly used as support for contents explored in school, as a complement. The design of theses educational systems must have the compromise to allow these users navigate and feel capable to explore every part of these interfaces. This paper is focusing the results of Ticese and Pedactice methods and shows the importance of these results as an exploratory phase in a bigger research that evaluates interfaces with children. Quantitative and qualitative data were collected related to structuring the user's mental model, influenced by the graphic representation of hypertext areas in a children's educational site. PMID- 22316824 TI - Ergonomic evaluation of postural stress in school workshop. AB - The objective of this study is to compare the evaluation of postural analysis between a self-report questionnaire and physical assessments methods for students aged 13 to 15 years old in school workshop. 336 students were volunteered as participants to fill in the questionnaire and being observed in the workshop. Total of 104 positions were selected and analyzed while students performing their tasks. Questionnaire data was examined to specify the prevalence of postural stress symptoms. The relationship of postural stress by physical assessment methods (RULA and REBA methods) was defined to identify the risk level of students' working posture. From the results, comparison of four factors categorized from total of 22 questions among ages, the mean values were lower for 13 years old students meaning that they were faced higher posture problems while using the workstation. The obtained results from both physical assessment methods and questionnaire analysis have identified 13 years old students faced higher risk exposure. Analysis results emphasized the fact that self-reports questionnaire method has almost accurate as postural evaluation methods to identify physical risks in workplace. The result also shows that an intervention is needed to overcome the posture problems. PMID- 22316825 TI - Usability issues in Learning Management Systems (LMS). AB - This project is about the usability of Learning Management Systems (LMS), focusing on the specific case of the open source system Moodle. Specifically, this project is about communication and collaboration tools that are used by teachers on the system. This study investigates whether usability problems hamper the use teachers make of these tools. Focused interviews were conducted with professionals working in distance education and the answers of the respondents were subjected to techniques of content analysis in order to obtain data for developing the tools needed to prove the hypothesis. PMID- 22316826 TI - A proposed model representing the relationships between user characteristics, computer exposure and musculoskeletal symptoms in children. AB - Children's computer exposure is rapidly growing. Several studies have suggested children using computers may be at risk of developing musculoskeletal symptoms. General models and theories relating to the causality of negative musculoskeletal outcomes in adult workers demonstrated relationships between workplace factors and musculoskeletal outcomes. When examining children's computer exposure it is evident that their use is different. Even though risk factors may be similar, due to the nature of children and their computer environments, the potential risk factors and thus a proposed model of causal relationships between exposure and outcomes may differ. OBJECTIVE: To develop a model of factors influencing computer exposure and musculoskeletal symptoms in children. METHODS: 1351 children (or their parents for Year 1 children) in school Years 1, 6, 9 and 11 (ages ~ 6,11,14,16 years) from 10 schools in Western Australia were surveyed on a range of user characteristics, computer exposure and musculoskeletal symptoms. RESULTS: Potential risk factors for childrens' computer exposure and musculoskeletal outcomes were multivariable. Factors such as age, gender, somatic complaints, flow, computer anxiety, computer, TV and physical activity exposure, and SES were related to computer exposure and children's reports of musculoskeletal symptoms. SIGNIFICANCE: Developing a child-related computer exposure model to understand relationships between potential risk factors and musculoskeletal symptoms will assist academics, teachers and parents to develop a better understanding of the risk factors for children's computer exposure. PMID- 22316827 TI - Children computer mouse use and anthropometry. AB - Studies have shown that increased computer use among adults in occupational settings is associated with the development of cumulative trauma disorders; however, the need to address how adult-sized mice and keyboards are affecting children is becoming increasingly important as both access to and use of computers is increasing among today's youth. To address the potential mismatch that exists between child stature and computer input device size and activation force, we have applied existing, age-specific, anthropometric data to elements of device design, including mouse size (length, width, height, switch location), and mouse-button activation forces. Trends supported the development of smaller computer input devices with lower activation forces for smaller statured individuals including children. Distinct and consistent trends in size delineations were seen across gender and age groups-trends that correlate well with grades and schooling in the United States education system . Three to four mouse sizes would be recommended: a mouse sized for adult and high school males; one for adult and high school females and junior high males; one for elementary school children, aged 6 to 10 years; and possibly a mouse for the smallest users who are less than six years old. PMID- 22316828 TI - Promoting healthy computer use among middle school students: a pilot school-based health promotion program. AB - BACKGROUND: Introduction of notebook computers in many schools has become integral to learning. This has increased students' screen-based exposure and the potential risks to physical and visual health. Unhealthy computing behaviours include frequent and long durations of exposure; awkward postures due to inappropriate furniture and workstation layout, and ignoring computer-related discomfort. OBJECTIVE: Describe the framework for a planned school-based health promotion program to encourage healthy computing behaviours among middle school students. METHODS: This planned program uses a community- based participatory research approach. Students in Year 7 in 2011 at a co-educational middle school, their parents, and teachers have been recruited. Baseline data was collected on students' knowledge of computer ergonomics, current notebook exposure, and attitudes towards healthy computing behaviours; and teachers' and self-perceived competence to promote healthy notebook use among students, and what education they wanted. The health promotion program is being developed by an inter professional team in collaboration with students, teachers and parents to embed concepts of ergonomics education in relevant school activities and school culture. End of year changes in reported and observed student computing behaviours will be used to determine the effectiveness of the program. SIGNIFICANCE: Building a body of evidence regarding physical health benefits to students from this school-based ergonomics program can guide policy development on the healthy use of computers within children's educational environments. PMID- 22316829 TI - An ergonomic study on the biomechanical consequences in children, generated by the use of computers at school. AB - This research deals with the influence of the computer use in schools related to the children posture, in an ergonomic point of view. The research tries to identify probable causes for the children early postural constraints, relating it to the sedentary behavior and the lack of an ergonomic project in schools. The survey involved 186 children, between 8 and 12 years old, students of a private school in Rio de Janeiro-Brasil. An historical and theoretical school furniture research was conducted as well as a survey with the students and teachers, computer postural evaluation, ergonomic evaluation (RULA method), and observations in the computer classroom. The research dealt with the student's perception with respect to the furniture utilized by him in the classroom during the use of the computer, his body complaint, the time he spent working on the school computer and the possibility of the existence of sedentariness. Also deals with the teachers' perception and knowledge regarding ergonomics with reference to schoolroom furniture and its Regulatory Norms (RN). The purpose of the research work is to highlight the importance of this knowledge, having in view the possibility of the teachers' collaboration in the ergonomic adaptation of the classroom environment and in their conscientious opinion during the purchasing of this furniture. A questionnaire was utilized and its results showed some discontent on the part of the teachers with relation to the schoolroom furniture as well as the teachers' scant knowledge of Ergonomics.We conclude with a survey that despite the children had constraints in postural assessments and school furniture needs a major ergonomic action, the time that children use the computer at school is small compared with the time of use at home and therefore insufficient to be the main cause of quantified commitments, thus the study of computer use at home as a development and continuity of this research. PMID- 22316830 TI - Primary school children's knowledge of, and attitudes towards, healthy computer use. AB - BACKGROUND: Australian children as young as five years are using computers in the home and school environments with increased frequency and longer duration as they age. Consequently, they may be exposed to risk factors for the development of physical health problems described in studies of adult computer users. To date schools have focused on providing children with the latest computer technologies; with far less attention given to appropriate workstations, ergonomics education and incorporating safe computing practices. By better understanding children's attitudes and knowledge, a directional approach to the development of an ergonomics education program may be established using a health promotion framework to encourage healthy computing behaviors. OBJECTIVE: The purpose of this study was to identify children's knowledge of, and attitudes towards healthy computing. METHOD: A cross-sectional inferential study of 537 Australian school children (aged 9 to 11 years) from Catholic Education Schools across Western Australia was conducted. Multiple logistic regression analyses identified that children's beliefs and attitudes about the negative health effects of computers were found to be most associated with unhealthy computing behaviors. RESULTS: Children lacked sufficient knowledge about the importance of postural and task variation, but had sufficient knowledge about adjusting workstation furniture specific to healthy computer use. PMID- 22316831 TI - Do teachers believe they are competent to promote healthy ICT use among their students? AB - BACKGROUND: Information and communication technologies (ICT), including computers, are becoming commonplace tools for learning by school children in Australia and around the world. Teachers are responsible for integrating ICT into the school learning environment; however, they may not recognize how and when ICT use may compromise their students' physical health. Children's exposure to physical harm through the unhealthy use of ICT may have liability implications for the education sector. OBJECTIVES: To determine (i) whether teachers consider it their responsibility to promote healthy ICT use among their students; (ii) teachers' self-perceived competence to do so; and (iii) what teachers perceive are the barriers and enablers to promoting healthy ICT use among their students. METHOD: An online survey was developed for the study. All Catholic Education school principals in Western Australia (n=157) were sent an email link to the survey for distribution to teachers at their respective schools. Over the three week survey period, 95 teachers completed the survey. Descriptive and inferential statistics were used to analyze the data and summarize participants' responses. RESULTS: Fifty-five percent of teachers agreed they were concerned about their students' physical health when using ICT. Only 19% of teachers reported they frequently or always provided their students with information on how to use computers in their class in a way, so as to promote physical health. Teachers identified barriers to promoting healthy computing use among students including; insufficient time (47%), non-adjustable furniture (46%), and insufficient knowledge (41%). Male teachers reported more confidence in their ability to promote healthy ICT use among students than female teachers. CONCLUSION: Just over half of the teachers in this study were concerned for the physical health of their students when using ICT in the classroom. Respondents identified barriers that limit their ability to promote healthy practices to their students. Designing and implementing school-based computer ergonomics education programmes may assist teachers fulfil their duty of care in regard to the physical health and well-being of their students. PMID- 22316832 TI - Postural assessment of school children: an input for the design of furniture. AB - During the last decades of the previous century, school desks with a tilt top have disappeared. The chairs have been designed for sitting upright, with the hip, knees and ankles all at right angles. However, the erect posture cannot be maintained for more than one or two minutes, after which it will result in fatigue, discomfort or poor posture. The main aim of project is to identify the type of furniture that most effectively contribute to adequate neck and back postures of the school children, by carrying out a postural analysis of a sample of school pupils when using three different types of furniture. The postures adopted by school pupils were monitored by video during several activities, such as reading, writing and painting tasks, copying from a blackboard and listening the teacher. Additionally, the characteristics of the adopted postures were assessed by registering the head tilt, flexion of the neck, trunk and hips position. All these aspects were classified and the results were recorded for future analysis. The obtained results seem to point out that the use of a school desk with a tilted table surface resulted in a reduction in trunk and neck flexion, preserving the natural lordosis in the lumbar and cervical regions. Accordingly, it can be concluded that there are alternatives to consider in the furniture design in order to eliminate tensions and, consequently, to improve children's wellbeing. PMID- 22316833 TI - Post occupancy evaluation of primary schools in Saudi Arabia. AB - The physical school environment has been shown to be important in helping children fulfill their academic potential and in providing appropriate working conditions for staff. However, few tools have been developed that enable multi stakeholder consultation which takes into account the opinions of young students. In Saudi Arabia there has been widespread investment in schools, but few guidelines have been provided to assist design or continuous evaluation. A Post Occupancy Evaluation (POE) method was developed and used to evaluate three international primary schools in Saudi Arabia. The methods identified weaknesses in the three schools and differences in responses from the three groups consulted (children, teachers and parents). Conclusions drawn from the study are that greater efforts need to be made to draw together research about how school facilities can support teaching and learning, increase effectiveness and levels of satisfaction. POE, when used in conjunction with checklists could be used as a means of driving up standards of educational facilities. PMID- 22316834 TI - Analysis of teacher's workspace in a child care center. AB - This paper presents one Post-Occupancy Evaluation (POE) done in a child care institution in the city of Florianopolis, in south of Brazil. The objective of this work is to analyze the environment's performance of the child care center considering the well-being of all of its users, with the mainly focus in the teacher's work. For this analyze, was used a multi methods approach, using consecrated evaluations in the area of environmental psychology and ergonomic. The methods used were: Exploratory Visit, Walkthrough, Questionnaires, Observations, Ergonomic Analyze and Poem of Wishes. The methodological procedures used enabled the identification of the main problems that committed the interaction between environment, user and task, which in addition to serve as an argument to the recommendations done to the analyzed Institution, form a repertory that can serve as a base to future projects in institutions with the same character. PMID- 22316835 TI - Educational workload and its psychophysiological impact on student organism. AB - It is described the method to study students' stability to perform learning tasks under impact of internal and external factors that includes special tests of performance (cognitive, perceptual, strength and mobility of neural processes, selfassessment, questionnaires) and measurement of physiological parameters in parallel (EEG and/or REG, heart rate, blood pressure). It was confirmed high self descriptiveness of fluctuation structure of test tasks performance in relation to the physiological "cost" of performance and subjective assessment of mood and capacity. It was revealed a high relationship both rate and accuracy indices of test performance with parameters of speed and density of solar wind that has individual dependence on lag between those parameters with time and had more significant meaning comparing to over-week education workload. PMID- 22316836 TI - Backpacks and school children's obesity: challenges for public health and ergonomics. AB - This descriptive study of cross sectional has focused on analyzing the school material weight transported by students associated with children and adolescents overweight in primary and secondary schools. Participants 339 students of both genders, aged 10-19 years. 243 students carrying and average load of 12.65% of his body weight. 53 students were overweight with a BMI of 20,00 to 35,6. 20 overweight students carrying backpacks more than 10% of his body weight. 21% of the students rated complained of back and shoulder pain. This data is very important in the preventive aspects for the individuals studied, as well as others with the same anthropometric characteristics and the same demand. PMID- 22316837 TI - Anthropometric aspects of body seated in school. AB - This study aimed to assess the student-furniture interface from anthropometric parameters of the sitting posture. The sample was composed of 887 students from two public schools in the State of Parana-Brazil, which attended children from 7 to 17 years of age. The data collection used anthropometric measures of the sitting position, a questionnaire containing a human body diagram for indication of discomfort areas and photographic records to verify postural and ergonomic inadequacies in classroom. The following anthropometric variables were measured: popliteal height, sacro-popliteal length, hip width, lumbar support height, and elbow and thigh height. Percentiles 5 and 95 of anthropometric variables showed differences statistically significant, with variation coefficient greater than 30%. In relation to body discomfort, the highest occurrences were recorded for ankle, knees and shoulder joints as well as for spine and buttocks. It was concluded that children use school furniture that does not meet their anthropometric standards, which favored the adoption of incorrect postures and contributed to the emergence of musculoskeletal problems that can interfere with their educational process. PMID- 22316838 TI - The use software ERGOSHOW in the education of health and safety at work to regardin the safety to children. AB - It is believed that health and safety of workers should be worked with children and early teenagers, the perspective that adults are more aware of these issues by providing them with health and quality of life in their daily lives, this is want the ERGOSHOW. The choice of media means for transmitting content of Ergonomics, Health and Safety (OSH) is justified because of the great popularity of computer games are among the public of the study, thereby providing a greater assimilation of the content worked. Therefore, the aim of this study was to work with OSH issues related to children between 08 and 12 years old, city of, State of Minas Gerais, Brazil. To achieve this we used the software ERGOSHOW, quizzes, and lecture. One can see that the use of multimedia tools in the learning, especially when considering the reports of mothers according to the different behavior of children after the development of activities, such as parents in correcting posture in relation to computer use. PMID- 22316839 TI - Effects of a school based exercise program on children's resistance and flexibility. AB - The aim of this study was to evaluate the short term effects of an exercise program on abdominal and back muscles resistance and hamstring flexibility among schoolchildren. Fifty eight healthy schoolchildren were divided into two groups: experimental (15 males and 14 females; mean age 12.2(1.8 years) and control (14 males and 15 females; mean age 11.9(2.1 years). The intervention was performed twice a week, on nonconsecutive days, during six weeks. The duration of each session was fifty minutes and they were composed by warming up aerobic exercises, isotonic and isometric abdominal and back muscle exercises and hamstring stretching. The intervention effects were evaluated through Kraus-Weber test (abdominal resistance), modified Biering-Sorensen test (back muscle resistance) and sit and reach test (hamstring flexibility). Data were analyzed by mixed design two-way ANOVA, with one between-subjects and one within-subject (time) factors. The alpha level was set at P<=0.05. The experimental group improved back muscles resistance and hamstring flexibility, but not abdominal muscles resistance. There was a significant interaction between groups and time for back muscles resistance (P=0.018) and for hamstring flexibility (P=0.017). The 6-week training period showed positive results in improving back muscles resistance and hamstring flexibility of schoolchildren. PMID- 22316840 TI - Back pack injuries in Indian school children: risk factors and clinical presentations. AB - The use of backpack increased substantially among the school children. Studies have shown that carrying a backpack cause to develop different symptoms of musculoskeletal disorders among the carrier of the backpack. In India there are fewer studies available in literature which explains the musculoskeletal discomfort among the school children. This study aimed at to find out the prevalence of different musculoskeletal problems among the school children. In a retrospective study data were collected for twenty two students. The main diagnostic criteria were pressure mark (redness or swelling) over neck and shoulder corresponding to the straps of the backpack, stooping posture while carrying the back pack, pain or stiffness in the neck, upper back and shoulders predominantly while carrying the back pack and absence of these symptoms during school holidays. Results revealed that pain in the upper back (40%), neck (27%) and shoulder (20%) were most prevalent body regions followed by forearm and wrist pain (7%) and low back (6%). Results further revealed that all the students participated in this study have a pressure mark over shoulder. 54.55% of the children were diagnosed with myofascial pain and rest with thoracic outlet syndrome. PMID- 22316841 TI - Children and teenagers working in artistic labor: Brazilian situation and international examples. AB - This descriptive study about children and adolescents artistic labor verifies the applicable legislation, in Brazil, regarding the participation of children and adolescents in the entertainment industry and in advertising campaigns, as well as the judicial processes about the theme known by the Brazilian Superior Court of Justice up to October, 2010. The results permit to conclude that, due to the lack of specific regulation and general rule of child labor prohibition, the restrictions that tend to protect the health and security of children and adolescents that act in the artistic niche (television, advertising, fashion, movies etc.) have been, in Brazil, at subjective criteria of the judges and, in many cases, in the hands of producers themselves. Brief considerations on how other countries regulate the theme are also presented (the USA, Portugal and Argentina). PMID- 22316842 TI - Embedded systems engineering for products and services design. AB - Systems engineering (SE) professionals strive to develop new techniques to enhance the value of contributions to multidisciplinary smart product design teams. Products and services designers challenge themselves to search beyond the traditional design concept of addressing the physical, social, and cognitive factors. This paper covers the application of embedded user-centered systems engineering design practices into work processes based on the ISO 13407 framework [20] to support smart systems and services design and development. As practitioners collaborate to investigate alternative smart product designs, they concentrate on creating valuable products which will enhance positive interaction. This paper capitalizes on the need to follow a user-centered SE approach to smart products design [4, 22]. Products and systems intelligence should embrace a positive approach to user-centered design while improving our understanding of usable value-adding, experience and extending our knowledge of what inspires others to design enjoyable services and products. PMID- 22316843 TI - Integrating ergonomics in design processes: a case study within an engineering consultancy firm. AB - This paper reports on a case study within an engineering consultancy firm, where engineering designers and ergonomists were working together on the design of a new hospital sterile processing plant. The objective of the paper is to gain a better understanding of the premises for integrating ergonomics into engineering design processes and how different factors either promote or limit the integration. Based on a grounded theory approach a model illustrating these factors is developed and different hypotheses about how these factors either promote and/or limit the integration of ergonomics into design processes is presented along with the model. PMID- 22316844 TI - Questionnaire survey of customer satisfaction for product categories towards certification of ergonomic quality in design. AB - Customer satisfaction was surveyed for 6 product categories (consumer electronics, daily commodities, home equipment, information systems, cars, and health appliances) by questionnaires based on the Analytic Hierarchy Process. Analyzing weight of evaluation factors, the 6 product categories were reorganized into 4 categories, those were related to 4 aspects in daily living that formed by two axes: home living - mobility life and healthy life - active communication. It was found that consumers were attracted by the actual user test by public institutes for all product categories. The certification based on the design process standard established by authorities, such as EQUID was the second best attractor for consumers. PMID- 22316845 TI - Product functions: interfaces with ergonomic design. AB - In addition to technical quality, increasing emphasis is being placed on the importance of elements such as the appearance and meaning of products. To be successful, therefore, attention must be paid to the aesthetic and symbolic functions of objects as well as to reliability and physical quality. Study of the interfaces of these functions may provide a theoretical basis for the ergonomic design of products. The objective of this review is to attempt to establish the nature of these interfaces. PMID- 22316846 TI - Kaizen and ergonomics: the perfect marriage. AB - This paper is an approach of how Kaizen (Continuous Improvement) and Ergonomics could be implemented in the field of work. The Toyota's Team Members are the owners of this job, applying tools and techniques to improve work conditions using the Kaizen Philosophy in a QCC Activity (Quality Control Circle). PMID- 22316847 TI - Similar methodological analysis involving the user experience. AB - This article deals with the use of a protocol for analysis of similar methodological analysis related to user experience. For both, were selected articles recounting experiments in the area. They were analyze based on the similar analysis protocol and finally, synthesized and associated. PMID- 22316848 TI - Designing with users to meet people needs: a teaching model. AB - Being in a context of great transformations of the whole system company-product market, design becomes interpreter of the society and strategic key-point for production realities. Design must assume an ergonomic approach and a methodology oriented to product innovation where people are the main focus of the system. Today it is visible the need for a methodological approach able to include the context of use employing user's "creative skills". In this scenario, a design educational model based only on knowledge doesn't seem to be fulfilling; the traditional "deductive" method doesn't meet the needs of new productive assets, here the urgency to experiment within the "inductive" method for the development of a method where to know and to know how, theory and practice, act synergistically. The aim is to teach a method able to help a young designer to understand people's needs and desires considering both the concrete/cognitive level and the emotional level. The paper presents, through some case studies, an educational model developed combining theoretical/conceptual and practical/applicatory aspects with user experiential aspects. The proposed approach to design enables the students to investigate users' needs and desires and helps them proposing innovative ideas and projects better fitting today's market realities. PMID- 22316849 TI - The importance of user centered design methods applied to the design of a new workstation: a case study. AB - This paper presents a case study of the application of user centered design methodologies in the product development for a line of ergonomic office furniture. The study aimed to analyze the experience of using a workstation from the perspective of two groups of users, installers and end users. The observation of users in their natural context of use not only allowed the development team to identify key needs and strategies of the users, transforming them into design solutions, but mainly it warned them of the importance and impact of user involvement in the product development cycle. PMID- 22316850 TI - The amount of ergonomics and user involvement in 151 design processes. AB - Ergonomics, usability and user-centered design are terms that are well known among designers. Yet, products often seem to fail to meet the users' needs, resulting in a gap between expected and experienced usability. To understand the possible causes of this gap the actions taken by the designer during the design process are studied in this paper. This can show whether and how certain actions influence the user-friendliness of the design products. The aim of this research was to understand whether ergonomic principles and methods are included in the design process, whether users are involved in this process and whether the experience of the designer (in ergonomics/user involvement) has an effect on the end product usability. In this study the design processes of 151 tangible products of students in design were analyzed. It showed that in 75% of the cases some ergonomic principles were applied. User involvement was performed in only 1/3 of the design cases. Hardly any correlation was found between the designers' experience in ergonomic principles and the way they applied it and no correlations were found between the designers' experience in user involvement and the users' involvement in the design process. PMID- 22316851 TI - VoiceYourView: anytime, anyplace, anywhere user participation. AB - Citizens are increasingly called upon to comment on issues that directly concern them. However, such consultations may be tokenistic [1] as they occur with limited respondents, or may be at a time, or in a format which is inconvenient to the user. To encourage wider participation, the VoiceYourView project (vYv) has developed a system allowing people to make comments in a manner, time and place convenient to them. A real world trial of the prototype system was conducted at Coventry University campus to explore issues related to the system's usability and usage, as a means of enabling campus users to comment on their environment. Members of the university population were invited to comment on the university estate using one of five technologies (e-mail, online form, iPhone app, SMS message, or electronic kiosk). Although the immediate application area in this case was the design of public spaces, the approach can be transferred to other domains and thus provide a new way of gathering user information. Submitted comments were automatically analysed in terms of theme, sentiment, location and actionability and displayed online in a 2D visualisation. It is argued that that online data collection (crowd sourcing and skimming social networks) may provide a rich source of information for future ergonomists. PMID- 22316852 TI - A methodology for connecting user centered design (UCD) with eco-design. The possibility of migration of products to services based on the user acceptance. AB - The consumer products generation is one of the main engines that fuel the planet's environmental problems, reduction of environmental impacts associated with the products has been studied from various aspects between them, the supply of products for public consumption instead of private, seeking to meet the needs of the community by establishing programs for sharing single product. It has been detected a problematic issues linked to this strategy, where the user acceptance of this new way of living together with the products must be achieved. The arguments here presented seek to identify user perception of such proposals and their possible acceptance throughout strategies from the User Centered Design (UCD). PMID- 22316853 TI - Design for Usability; practice-oriented research for user-centered product design. AB - The Design for Usability project aims at improving the usability of electronic professional and consumer products by creating new methodology and methods for user-centred product development, which are feasible to apply in practice. The project was focused on 5 key areas: (i) design methodology, expanding the existing approach of scenario-based design to incorporate the interaction between product design, user characteristics, and user behaviour; (ii) company processes, barriers and enablers for usability in practice; (iii) user characteristics in relation to types of products and use-situations; (iv) usability decision-making; and (v) product impact on user behaviour. The project team developed methods and techniques in each of these areas to support the design of products with a high level of usability. This paper brings together and summarizes the findings. PMID- 22316854 TI - The inclusion of ergonomic tools in the informational, conceptual and preliminary phases of the product design methodology. AB - The process of product development has received special attention as it is being recognized as a source of competitive gain. Through its systematic use companies reduce costs, increase quality and decrease development time. However, one can find products being launched on the market that cause dissatisfaction to its users, and in consequence if the customer feels harmed or injured he will no longer purchase a product from the same brand. This in regard only to the commercial aspect; usually the danger of an accident or injury is not even thought about. This paper is the basis of the dissertation master's degree and used a literature research to build the repertoire, analyzing the methodologies applied by product design engineers, designers and ergonomists. The analysis results demonstrate the inefficiency of the design methodologies ergonomic issues. The contribution of this work lies in the suggestion to include ergonomic tools in all phases of product development and the presentation of a table with the tools that points out its most suitable time of application and results. PMID- 22316855 TI - Ergonomics and usability of children interfaces: Spore(r), the case study. AB - This study supports itself in ergonomic concepts and usability criteria by prioritizing the identification and correction of problems found during the interaction of children with projected interfaces for them and left from the cognitive, interactional and interfacial difficulties caused by the excesses of color, elements and animation in sites and games, between them the difficulty of recognition of the information during the interaction with the elements of grid of the interface. The results of the methodology had proven that 78.38% of the 37 children got so absorbed by the game and forgot to fulfill their tasks, at least partially, and that the application of the supported ergonomic beddings in usability criteria is imperative. It is relevant to point out that the projetual activity of the game is centered in the user, the child, whose behavior is distinct and particular. Points that had been disclosed that had passed unobserved by the involved adults in this project, and that they had displayed the unappropriateness of some screens of the Spore(r) to the etaria band due to the ambiguity of the game, besides, the children had been sensible to the clarity in some screens and had passed for unnecessary situations of stress. PMID- 22316856 TI - A children, teachers and designers as evaluators of usability of educational software. AB - This article sets out to discuss the results of evaluations of usability made by children, teachers and designers through methods targeted on their profiles and contexts of use. Based on a survey of methods for evaluating usability, a field study was conducted in which such users--stakeholders--explored the educational software called "Mundo da Crianca" ("Child's World"). The focus of this study was the analysis of this system and principally of the appropriateness of methods as to the avenues they suggest such users and contexts might explore. PMID- 22316857 TI - A literature review about usability evaluation methods for e-learning platforms. AB - The usability analysis of information systems has been the target of several research studies over the past thirty years. These studies have highlighted a great diversity of points of view, including researchers from different scientific areas such as Ergonomics, Computer Science, Design and Education. Within the domain of information ergonomics, the study of tools and methods used for usability evaluation dedicated to E-learning presents evidence that there is a continuous and dynamic evolution of E-learning systems, in many different contexts -academics and corporative. These systems, also known as LMS (Learning Management Systems), can be classified according to their educational goals and their technological features. However, in these systems the usability issues are related with the relationship/interactions between user and system in the user's context. This review is a synthesis of research project about Information Ergonomics and embraces three dimensions, namely the methods, models and frameworks that have been applied to evaluate LMS. The study also includes the main usability criteria and heuristics used. The obtained results show a notorious change in the paradigms of usability, with which it will be possible to discuss about the studies carried out by different researchers that were focused on usability ergonomic principles aimed at E-learning. PMID- 22316858 TI - Usability in product design--the importance and need for systematic assessment models in product development--Usa-Design Model (U-D) (c). AB - In product design, human factors are considered as an element of differentiation given that today's consumer demands are increasing. Safety, wellbeing, satisfaction, health, effectiveness, efficiency, and other aspects must be effectively incorporated into the product development process. This work proposes a usability assessment model that can be incorporated as an assessment tool. The methodological approach is settled in two stages. First a literature review focus specifically on usability and developing user-centred products. After this, a model of usability named Usa-Design (U-D(c)) is presented. Consisted of four phases: understanding the use context, pre-preliminary usability assessment (efficiency/effectiveness/satisfaction); assessment of usability principles and results, U-D(c) features are modular and flexible, allowing principles used in Phase 3 to be changed according to the needs and scenario of each situation. With qualitative/quantitative measurement scales of easy understanding and application, the model results are viable and applicable throughout all the product development process. PMID- 22316859 TI - Common criteria for usability review. AB - The propose of this paper is to present a literature review, in a grouping of common criteria for usability approaches of Bastien and Scapin (1993), Nielsen (1994), Shnneiderman(1998), Dix et al (1998), Preece et al (2005) and ISO 9241 110 (2006). After establishment of prerequisites for knowledge of the general characteristics of the users who will use the system, are defined and explained the criteria in common: consistency, user control, ease of learning, flexibility, errors management, reduction of excess and visibility system status. Although there is no determination as to which criteria should be considered when developing an interface and each author presents some specificity in their approach, it is observed that there is equivalence in the measures adopted usability. PMID- 22316860 TI - Usability analysis of industrial cooking equipment. AB - This paper refers to the comparative study of the equipment used for cooking in commercial of kitchens restaurants that use the system of traditional cooking and those ones which use the system called smart cooking (combination oven). The study investigates the usability issues concerning to the two systems, analyzing comparatively the aspects related to anthropometry, dimensional variables, the use of the product and also the product safety, as well as issues of information related to operation of the new concepts of cooking in intelligent systems. PMID- 22316861 TI - The methodological involvement of the emotional design and cognitive ergonomics as a tool in the development of children products. AB - To demonstrate the relationship between design and emotional development for kids, this article offers an initial approach about the definition and historical aspects of emotion in product development, citing the main authors of this issue. Based the field research conducted with children from 2 to 6 years of age, was also describes the basic ideas of Piaget in the child psychology and pre operational stage (age group studied) and the significance of children's toys from the perspective of Vigostsky. Using this theoretical framework and results of field research, we can infer some emotional design as advocated by the producers of positive affect on humans and its relationship with the child's development and choices of their toys. PMID- 22316862 TI - Emotion and interior space design: an ergonomic perspective. AB - Interaction between the users and their environment is spontaneous and unavoidable. This interaction can be positive or negative. A good interior space is about considering all the physical, environmental and cognitive elements and harmonizing them to make it a space that feels right, functionally and emotionally. The important element that has to be considered the most in an interior space is the "user". Balancing all these elements is a challenging job and results in a perfect interior space design. This paper intends to bring to light the necessity of designing an optimum interior space, which is a balance of the user's choice and the mandatory standards that ought to be followed for user safety and convenience. There has to be an intervening domain of ergonomics which will guide to bring out a balance between the personal choice of the user and the usual standards followed. It should also provide a step-by-step information, guidance and direction to act to the specifications and standards systematically to adapt an integrated approach of handling all the elements holistically which will indeed result in a good interior space. PMID- 22316863 TI - Aesthetic taste versus utility: the emotional and rational of the individual. AB - This article explores the development of an aesthetics framework that aims to provide designers with parameters to understand emotion, taste, and aesthetic judgment under their own cultural influence. This framework will equip designers with tangible criteria for judging cultural influences that have an impact on industrial design while preventing designers from adopting subjective options or being "followers of the current trend." To address the complexity of the topic, a systemic approach is taken so as to be able to capture its several elements. Therefore, the aesthetics framework adopts a systemic approach, which enables its constituents to be compared and the interplay or "links" between these different elements to be identified. PMID- 22316864 TI - Infant feeding: the interfaces between interaction design and cognitive ergonomics in user-centered design. AB - This text presents a discussion on the process of developing interactive products focused on infant behavior, which result was an interactive game for encouraging infant feeding. For that, it describes the use of cognitive psychology concepts added to interaction design methodology. Through this project, this article sustains how the cooperative use of these concepts provides adherent solutions to users' needs, whichever they are. Besides that, it verifies the closeness of those methodologies to boundary areas of knowledge, such as design focused on user and ergonomics. PMID- 22316865 TI - Product evaluation based in the association between intuition and tasks. AB - This paper explores the importance of researching the intuitiveness in the product use. It approaches the intuitiveness influence for users that already had a visual experience of the product. Finally, it is suggested the use of a table that relates the tasks performed while using a product, the features for an intuitive use and the performance metric "task success". PMID- 22316866 TI - Design of experiment with emphasis on intuitive use. AB - The article presents a step in the design of an experiment that has an emphasis on the following research question: how to assess the user friendliness of products in use? For this purpose, we developed three different approaches involving the use of products in intuitiveness. In this table, were removed some information regarding the positive aspects. These were broken down into procedures to be performed for an experiment with the same scope. PMID- 22316867 TI - Design for reflection. AB - Since a few years, a number of academic papers have been proposing to shift from user-centered design to human-centered (or person) design. In this contribution, we discuss as the common tread underlying these works the idea that design should also address the reflective part of our human experience, and not only aim to maximize the experiential aspects. Our review is complemented with examples derived from the internet world and from ICT consumer products. The main research areas we see as promising for the approach of "design for reflection" are: design for pauses, design for detachment, design for serendipity. PMID- 22316868 TI - Evaluating insole design with joint motion, plantar pressure and rating of perceived exertion measures. AB - This study compared a newly-designed insole with two commercially available insoles. The response measures included joint motion, plantar pressure and rating of perceived exertion. Thirty healthy female students were paid to participate in this study. The results showed that significant differences among the three insoles were found in plantar pressure and rating of perceived exertion. There were no significant differences among three different insoles in join motion measures. When wearing the newly-designed insole, the plantar pressure under heel area would transfer to midfoot area, and resulted in lower subjective discomfort ratings in midfoot and heel areas. The barefoot condition showed the worst performances in most of the response measures. The findings of this study provide very useful information for ergonomic insole design. PMID- 22316869 TI - A mind in a disk: the attribution of mental states to technological systems. AB - This paper reports a study about the role of different variables in the process of attributing mental states to technological systems, variables such as the number of figural elements displayed in the system and the personality traits of the subjects interacting with the systems. In an experiment, participants were interacting with a computer on whose screen several disks of various sizes and colours were blinking at different rates. Each time a disk reappeared on the screen its position was randomly varied. As in a videogame, participants had to click on the disks to increase their score. The results showed that, even in the case of such a simple system, subjects believed that the figural elements they were interacting with had some form of mental states, although their confidence in these beliefs varied in the different experimental conditions. The confidence level of the attributions, in fact, was not the same for all the different mental states considered, and it varied also both with the number of elements being displayed as well as with some personality traits of the subjects. PMID- 22316870 TI - User's demography and expectation regarding search, purchase and evaluation in mobile application store. AB - This article is result from a questionnaire about mobile app store usage. The objective of this work was to collect information about user needs and opinion regarding search, purchase and evaluation process in Android Market, Apple App Store, BlackBerry App World and Nokia Ovi Store. The data collected was analyzed to identify the positive and negative usability aspects, if the process to perform these task are any different in those stores and if the users are satisfy with their store or if they have any complains about it. Its covers the brazilian market only. PMID- 22316871 TI - Exploring the requirements for multimodal interaction for mobile devices in an end-to-end journey context. AB - The paper investigates the requirements for multimodal interaction on mobile devices in an end-to-end journey context. Traditional interfaces are deemed cumbersome and inefficient for exchanging information with the user. Multimodal interaction provides a different user-centred approach allowing for more natural and intuitive interaction between humans and computers. It is especially suitable for mobile interaction as it can overcome additional constraints including small screens, awkward keypads, and continuously changing settings - an inherent property of mobility. This paper is based on end-to-end journeys where users encounter several contexts during their journeys. Interviews and focus groups explore the requirements for multimodal interaction design for mobile devices by examining journey stages and identifying the users' information needs and sources. Findings suggest that multimodal communication is crucial when users multitask. Choosing suitable modalities depend on user context, characteristics and tasks. PMID- 22316872 TI - The ergonomic evaluation of a virtual learning environment usability. AB - The article presents the processes and the results of the application of some ergonomic techniques, used to evaluate the usability of the virtual learning environment adopted by the Distance Education Center of the Federal Institute of Espirito Santo - Brazil. PMID- 22316873 TI - Risk factors and clinical features of text message injuries. AB - Use of mobile phone and sending text message is a very common in today's life. While sending a text message the users need to use their thumb and other palm muscles extensively. The thumb most of the time adducted on the key pad of the mobile and use high force to type the letters. Studies in literature showed that text messaging has an adverse effect on musculoskeletal system of hand. But the extensive study on the type of disorders set in among the users who extensively use mobile phone for texting. This study aims at to evaluate risk factor and clinical feature of the MSD due to hand held devices. Twenty seven subjects participated in this study. Predefined protocols were used to evaluate type of MSD occurred among the subjects. The study revealed that development of tendinitis in extensor pollicis longus, myofascial pain syndrome (70.37%) of adductor pollicis, 1st interossei and extensor digitorum communis . Other associated problems diagnosed were thoracic outlet syndrome (51.85%), fibromyalgia syndrome (25.93%), hypothyroidism (7.41%), wrist tendinitis (14.81%) and De Quervain's syndrome (7.41%). It has been observed that the pathology were tendinitis of extensor pollicis longus, myofascial pain syndrome of thenar muscles and 1st interossei, extensor digitorum communis. PMID- 22316874 TI - Using environmental affordances to direct people natural movement indoors. AB - Understanding and predicting people's displacement movement is particularly important for professionals involved in planning complex buildings (e.g., hospitals, convention centers, subway stations and university campus). Some decisions taken by the visitors while choosing what route to follow can be influenced by some environmental cues which can act as a factor of attraction, influencing the wayfinding process. Therefore, the main objective of this study was to evaluate the hypotheses that, in the context of a simulated emergency egress, people prefer to move along either a wider and with more lighting corridor or to bear right. To collect the users' responses, a constant stimulus method was used, combined with a two forced choices method, involving the projection of stereoscopic images in a wall-screen. Results suggest that, in a "T type" intersection, users randomly chose which direction to follow. However, if there is an increment in the width of the side corridor, users tend to follow the wider corridor. When light is inserted, users also prefer to choose the corridors with more lighting. In situations where the variables corridor width and existence of lighting are concurrent, the corridors with light are the most chosen by the users. PMID- 22316875 TI - Participatory design in the project of virtual learning environment of histology. AB - This present article describes a research on the development, under the approach of participatory design, a virtual teaching-learning of Histology in which students and teachers participated actively in all stages of development of the educational environment. We postulates that the development of virtual learning environment of Histology, through the Participatory Design approach, contributes to greater acceptance and use by students and that the adoption of virtual environment for teaching and learning by teachers is a determining factor of use by students. PMID- 22316876 TI - Developing an usability test to evaluate the use of augmented reality to improve the first interaction with a product. AB - Developing an usability test involves defining the metrics that are being evaluated, the methods used and the right tasks to be performed to achieve the objectives from the usability test. This article presents the development of an usability test aimed to evaluate the experience while first interacting with a product by using the augmented reality technology. This usability test is part of a bigger research that aims to evaluate if the use of augmented reality helps the process of learning how to use a new product. The paper starts with a literature review of related works, explaining many of the tools developed for evaluating usability tests. This section is followed by a methodological explain and the description of the developed usability test itself. The conclusion presents suggestions of further improvements. PMID- 22316877 TI - Use of augmented reality in the usability evaluation of products. AB - Many characteristics of a product are evaluated during the development phase, such as function, aesthetics and manufacturing. The conception phase is supported by drawings and computer graphics, followed by physical prototypes that help evaluating the product features. The augmented reality technology has a great potential to assist the designers in this phase, reducing the development process time and costs and improving the quality of the evaluation. This paper presents a study that intends to investigate the suitability of using augmented reality to evaluate the usability of electronic products. PMID- 22316878 TI - How to reduce workload--augmented reality to ease the work of air traffic controllers. AB - In the future the air traffic will rise--the workload of the controllers will do the same. In the BMWi research project, one of the tasks is, how to ensure safe air traffic, and a reasonable workload for the air traffic controllers. In this project it was the goal to find ways how to reduce the workload (and stress) for the controllers to allow safe air traffic, esp. at huge hub-airports by implementing augmented reality visualization and interaction. PMID- 22316879 TI - Ergonomic evaluation of novel tool for snap-off the neck of ampoule. AB - Needlestick and Sharps Injuries (NSI) represent an important workplace issue in contemporary health care. Present study provided the new method to snap-off the neck of sealed ampoule. The idea of novel opener tool is prepare the grinding slice inside rubber ring, so users could put the ampoule inside the rubber ring and then rotated the rubber ring to snap-off the neck of ampoule. The purpose of present study was evaluated the methods of snap-off and sizes of ampoule on forearm muscle activities, wrist postures and performance. The pronator teres muscle were heavier load as increased the sizes of ampoule. For performance analysis, Duncan's multiple range tests indicated that time of snap-off were longer in 10 ml and 20 ml of ampoule. The EMG of pronator teres muscle was significantly affected by methods of snap-off. Duncan's multiple range tests indicated that lower load was experienced on forearm muscles while using grinding slice with glove. For wrist posture, the ranges of motion for wrist were significant lower while using the novel tool. Present study provided the novel tool effectively to snap-off the ampoule to decrease forearm workload and sharp injuries. PMID- 22316880 TI - Product perception from sensory stimuli: the case of vacuum cleaner. AB - This paper discusses the importance of consideration of different sensory stimuli in the perception of the product. So we conducted an experiment that examined whether there is a difference between the perception of sensory stimuli from artificially isolated. The result is an analysis of the different sensory modalities, relating them to product an between them. PMID- 22316881 TI - The technological obsolescence of the Brazilian eletronic ballot box. AB - The electronic ballot box has played a significant role in the consolidation of Brazilian political process. It has enabled paper ballots extinction as a support for the elector's vote as well as for voting counting processes. It is also widely known that election automation has decisively collaborated to the legitimization of Brazilian democracy, getting rid of doubts about the winning candidates. In 1995, when the project was conceived, it represented a compromise solution, balancing technical efficiency and costs trade-offs. However, this architecture currently limits the ergonomic enhancements to the device operation, transportation, maintenance and storage. Nowadays are available in the market devices of reduced dimensions, based on novel computational architecture, namely tablet computers, which emphasizes usability, autonomy, portability, security and low power consumption. Therefore, the proposal under discussion is the replacement of the current electronic ballot boxes for tablet-based devices to improve the ergonomics aspects of the Brazilian voting process. These devices offer a plethora of integrated features (e.g., capacitive touchscreen, speakers, microphone) that enable highly usable and simple user interfaces, in addition to enhancing the voting process security mechanisms. Finally, their operational systems features allow for the development of highly secure applications, suitable to the requirements of a voting process. PMID- 22316882 TI - Designing an ergonomics backpack for student aged 7-9 with user centred design approach. AB - Researches explored that backpacks are the most common means of carrying school supplies for students. Carrying heavy backpacks causes a wide range of disorders such as musculoskeletal disorders and postural malfunction. User Centered Design has proven its suitability to produce high efficient products with the most adaptability to consumer demands. This approach combined with consideration of normal standards and ergonomics features, with the recognition of children's needs and requirements, has been used in this research to prepare an initial design of a backpack. After that, its prototype was manufactured. The backpack was tested by 120 elementary students in three steps of form, ergonomics and load sense. A redesign was performed that has applied the results of the test run. Results showed that this new backpack can considerably reduce the effective loads on the shoulders, back and neck. PMID- 22316883 TI - The role of usability in the evaluation of accidents: human error or design flaw? AB - This article aims to highlight the role of consumer products companies in the heart and the extent of accidents involving these types of products, and as such undesired events take part as an agent in influencing decision making for the purchase of a product that nature on the part of consumers and users. The article demonstrates, by reference, interviews and case studies such as the development of poorly designed products and design errors of design can influence the usage behavior of users, thus leading to accidents, and also negatively affect the next image of a company. The full explanation of these types of questions aims to raise awareness, plan on a reliable usability, users and consumers in general about the safe use of consumer products, and also safeguard their rights before a legal system of consumer protection, even far away by the CDC--Code of Consumer Protection. PMID- 22316884 TI - Exergames: the role of ergonomics and design in helping to control childhood obesity through physical and functional exercise program. AB - In the area of the design and physiotherapy, the using of virtual technologies for immersion of users are spreading. And this affirmation extends to several areas of knowledge. In games, the quote is, resources are being used to work cognitive skills, attention, memory, among other factors beside the children. Currently, at the expense of usability, low cost, virtual technologies of perception and interaction, as Nintendo Wii, X-Box 360, among others, arises therefore a new class of games called Exergames, which is the union of physical activity the game. This fact gives users the development of sensory and motor skills through virtual reality mechanisms suitable for certain needs. This literature review aimed to provide an overview of the current context of Exergames, especially in use for controlling childhood obesity, which is growing alarmingly, with some features, applications and possibilities for use at the design and other areas such as physiotherapy. PMID- 22316885 TI - End users "Feedback" to improve ergonomic design of machinery. AB - This paper describes the Feedback method designed to collect the contribution of users for the reconstruction and comprehension of the actual work and real activity for the improvement of the technical standards, design, manufacturing and use of machinery. The Feedback method has since now been applied successfully - in collaboration with public authorities, market surveillance bodies, social partners organization and technical institutes - to five different types of machines: woodworking machinery, forklift trucks, angle grinder and combine harvester. After ten years of experimentation in seven European countries Feedback has proved to be trans-nationally comparable and has attracted the interest of as much as 250 expert users - mostly workers, but also employers and technicians - who have shared their knowledge and experience by taking part in almost 30 working groups. The information collected with the Feedback method can be used by: -CEN and ISO standardization committees and working groups to become aware of the problems relating to the real use of specific machines in different work contexts, and thus to be able to draw up new or to revise existing standards accordingly; - Designers and manufacturers to produce better, more comfortable and safer machines and to provide precise instructions for use; - Employers, users and workers for training purposes and for defining appropriate work procedures; - Inspection bodies to enhance their knowledge and improve the efficiency of their interventions and advice. PMID- 22316886 TI - Comfort aspects important for the performance and safety of kitesurfing. AB - Equipment used in sports is of great importance, especially when the equipment is in direct contact with the athlete or is important for safety. In the sport kitesurfing environmental factors and the equipment design are crucial for the comfort and safety. The participants' choice and opinion of equipment can show which factors are considered most important for the performance and to reduce risk for injury. This study has evaluated self-reported information from the participants about what equipment they use, comfort of the equipment and if the equipment has contributed to any injuries. The methods used were questionnaires (n=206) and interviews (n=17), which in combination allows to assess the problem both quantitatively and qualitatively. The results showed that supported leading edge kites are most frequently used, with a waist harness and foot straps to attach the feet. The choice of kite type was mainly based on the discipline of riding for the respondent. Some issues concerning comfort of riding and injury risk the respondents did relate to the design of harness and foot straps. The information from this study can be used for development strategies for industry manufacturers and for further studies in the area of equipment design and biomechanics. PMID- 22316887 TI - A bus stop shelter evaluated from the user's perspective. AB - This study aims to evaluate the current bus stop shelter model used in Florianopolis, Brazil, through a functional analysis--focused in the relationship between the shelter, the users and their activities--and also to analyse users' perceptions. The methodology consisted of exploratory visits, anthropometric analysis, observation and interviews. The exploratory visit intended to survey the physical characteristics of the shelter (dimensions, materials, colors, displayed information) and its position on the sidewalk. The anthropometric analysis was made to verify whether the dimensions of the shelters were adequate to users' needs. The observation provided data for the analysis of users' behavior, which involved a biomechanical study of their postures, an ownership/occupancy analysis in terms of territoriality and studies about spatial requirements of interpersonal relations (proxemics). The interviews helped to analyze how the user perceives the quality of some of the main functions of the shelter: to provide physical and psychological comfort and to display information about the public transportation system. As a result, the overall conclusion is that shelters do not meet users' needs. Recommendations are provided in order to improve physical and psychological comfort and to display relevant information about the transportation system. PMID- 22316888 TI - Ergonomic basket design to reduce cumulative trauma disorders in tea leaf plucking operation. AB - Work related musculoskeletal disorders are seen as an indicating parameter of occupational stress among the women workers engaged in tea leaf plucking operation. The hand plucking (no mechanized plucking is practiced in Assam) being a highly repetitive task requires forceful exertions to reach to the distant periphery of the tea bushes and mechanical compression (pressing against hard surfaces). Specifically it aggravates with awkward positions adopted. The current research addresses to minimize the risk factors associated with CTDs and to ascertain the role of ergonomic design development in improving the situation. Women workforce engaged in tea industry in Assam suffer from back, shoulder, arm and finger pains. Workers perform the activity for 440 minutes in the entire shift with one hour lunch break in between in the garden itself. An ergonomic investigation aiming at studying the strain index of plucking operation in tea industry was conducted. While performing the operation workers were found to assume unnatural posture which is static as well as highly dynamic with a load (tea leaf collecting basket up to weight of 30 kg when filled with plucked leaves) at back. With gradual increment of load and pain though the load is released intermittently the strain level found to remain at a high level. The total QEC scores found for plucking activity was 110 out of 138. To improve the situation and to reduce the work related upper limb disorder (WRULD) an ergonomically designed basket was conceived and trial results showed improvements. The newly designed plucking basket fits the back curvature of the workers well, which keeps the basket in place unlike the existing round basket. The new basket is light in weight having more leaf capacity. Significant reduction in energy expenditure and MSDs suffered was observed while using improved basket over existing basket. PMID- 22316889 TI - Ergonomic evaluation of conventional and improved methods of aonla pricking with women workers. AB - Conventional and improved methods of aonla pricking were evaluated ergonomically on an experiment conducted for 20 minute with women workers. The working heart rate, energy expenditure rate, total cardiac cost of work and physiological cost of work with conventional tools varied from 93-102 beats.min-1, 6-7.5 kJ.min-1, 285-470 beats, 14 -23 beats.min-1 while with machine varied from 96-105 beats.min 1, 6.5-8 kJ.min-1 , 336-540 beats, 16-27 beats.min-1 respectively. OWAS score for conventional method was 2 indicating corrective measures in near future while with machine was 1 indicating no corrective measures. Result of Nordic Musculoskeletal Questionnaire revealed that subjects complaint of pain in back, neck, right shoulder and right hand due to unnatural body posture and repetitive movement with hand tool. Moreover pricking was carried out in improper lighting conditions (200-300 lux) resulting into finger injuries from sharp edges of hand tool, whereas with machine no such problems were observed. Output with machine increased thrice than hand pricking in a given time. Machine was found useful in terms of saving time, increased productivity, enhanced safety and comfort as involved improved posture, was easy to handle and operate, thus increasing efficiency of the worker leading to better quality of life. PMID- 22316890 TI - Design and technology in the development of potters' lathes for modeling with terracota: the case of Cabo de Santo Agostinho. AB - This article reports the experience of the design team of the Laboratory The Imaginary in the process of developing an electric potter's lathe which respects the biomechanics of the body, helps to development the task, maintains the archetype of traditional equipment, and improves the mechanical efficiency of the power transmission system. The design method used was based on the axes of research, analysis, development and monitoring, and focused on the product and with partners: the artisans and engineering and production teams. The main results point to ergonomic improvements in the biomechanical and dimensional aspects, and a decrease in the risk of accidents and occupational diseases. The experience of this case also highlights the gains arising from the relationship between design, engineering and users (artisans) in developing products with a design that can be easily replicated for other communities of potters in the state. This and other actions are part of the outlook of the Laboratory the Imaginary which in partnership with local authorities, wishes to see the craft activities continue and to give value to the culture of the city. PMID- 22316891 TI - The conception of fashion products for children: reflections on safety parameters. AB - The purpose of this study is to reflect on safety requirements for children's clothing, based on the standardization proposed by the ABNT (Technical Standardization Brazilian Association). Bibliographic research and case studies were considered on writing this work. We also discuss the importance of adding other safety requirements to the current standardization, as well as the increasing of the actual age range specified by the ABNT, following the children's clothing safety standardizations in Portugal and the United States, also stated here. PMID- 22316892 TI - Ergonomics analysis of the productive environment of fashion clothing firm in Belo Horizonte-MG. AB - A company making women's clothing, located in Belo Horizonte, Minas Gerais was studied in its ergonomic aspects with regard to the layout. With this study it was possible to establish the best positioning of machines and jobs of employees. The analysis criteria used were: frequency of use, functional grouping, sequence of use, flow and intensity of preferred connections. An ideal arrangement in the workplace provides improved manufacturing quality and employee performance and consequently higher production yields. PMID- 22316893 TI - Research on the relationship between the structural properties of bedding layer in spring mattress and sleep quality. AB - Mattress, as a sleep platform, its types and physical properties has an important effect on sleep quality and rest efficiency. In this paper, by subjective evaluations, analysis of sleeping behaviors and tests of depth of sleep, the relationship between characteristics of the bedding materials, the structure of mattress, sleep quality and sleep behaviors were studied. The results showed that: (1) Characteristics of the bedding materials and structure of spring mattress had a remarkable effect on sleep behaviors and sleep quality. An optimum combination of the bedding materials, the structure of mattress and its core could improve the overall comfort of mattress, thereby improving the depth of sleep and sleep quality. (2) Sleep behaviors had a close relationship with sleeping postures and sleep habits. The characteristics of sleep behaviors vary from person to person. PMID- 22316894 TI - Biomechanics-based active control of bedding support properties and its influence on sleep. AB - Proper body support plays an import role in the recuperation of our body during sleep. Therefore, this study uses an automatically adapting bedding system that optimises spinal alignment throughout the night by altering the stiffness of eight comfort zones. The aim is to investigate the influence of such a dynamic sleep environment on objective and subjective sleep parameters. The bedding system contains 165 sensors that measure mattress indentation. It also includes eight actuators that control the comfort zones. Based on the measured mattress indentation, body movements and posture changes are detected. Control of spinal alignment is established by fitting personalized human models in the measured indentation. A total of 11 normal sleepers participated in this study. Sleep experiments were performed in a sleep laboratory where subjects slept three nights: a first night for adaptation, a reference night and an active support night (in counterbalanced order). Polysomnographic measurements were recorded during the nights, combined with questionnaires aiming at assessing subjective information. Subjective information on sleep quality, daytime quality and perceived number of awakenings shows significant improvements during the active support (ACS) night. Objective results showed a trend towards increased slow wave sleep. On the other hand, it was noticed that % N1-sleep was significantly increased during ACS night, while % N2-sleep was significantly decreased. No prolonged N1 periods were found during or immediately after steering. PMID- 22316895 TI - Analysis of ergonomics conditions of a brand of mattress and pillows. University industry project, Medellin-Colombia. AB - This project presents an analysis of the ergonomic conditions of three types of mattress and three types of pillow. The products are manufactured by a Colombian company which specializes in flexible polyurethane foam and other products designed for rest and relaxation. The project was developed through the University - Industry relationship: a strategic partnership based on the knowledge and strengths of each component. The conceptual theories that underpin the Ergonomics Research Division of the Design Studies Research Group (GED) provided the methodological approach for the project: the characteristics, the requirements and the relationships that are established between the components that constitute the User - Product - Context system (basic principles of the Ergonomics - Design relationship). An important factor in the project was the conception and measurement of comfort. Comfort can be measured on an objective level (quantitative measurement), and on a subjective level (a user's particular perceptions and tastes). What constitutes 'comfort' can vary from person to person, thus making the identification of criteria for the standardization of consumer products problematic. This project enabled design recommendations to be made to the Company vis-a-vis future proposals for mattress and pillow products. This experience of applied research was carried out by professors and students from the Faculty of Industrial Design at the UPB in Medellin, Colombia. PMID- 22316896 TI - Body dimension measurements for pillow design for Taiwanese. AB - Study reported a pillow with a uniform height was not suitable for sleeping in supine and lateral positions. The study aims to determine the pillow dimensions for fitting supine and lateral positions for Taiwanese. Ten females and ten males subjects with a mean age of 21.9 years (SD= 1.07 years) participated in the study. Body dimensions of head, neck and shoulder in crown and sagittal planes were measured with the Martins' anthropometer and a curve measurer to determine the pillow's sizes. The results showed that the basic form of pillow for both genders is a U form from the front view. The middle area of the pillow is for supine position and the both side areas are for lateral positions. The base of pillow is a rectangle from the top view. The pillow is designed with a width of 75 and 70 cm for male and female, and a depth of 40 and 35 cm for male and female. The height in middle area and both side are 4 and 14 cm for male, and 2 and 12 cm for female. A neck rest with a height of 1.5 cm was proposed for neck support. PMID- 22316897 TI - Technology and cognitive ability: the use of new technologies and the design of digital interfaces. AB - This study is guided by the principle that there is no technology detached from an ideology. This ideology appears in the interfaces conditioning the relationship between people and digital artifacts. This article adopts as theoretical reference the User-Centered Design (UCD). Under the UCD principles it is presented a key to understand how technology is a vehicle of ideological content that affects the design practices. PMID- 22316898 TI - Comparison between static maximal force and handbrake pulling force. AB - The measurement of maximum pulling force is important not only for specifying force limit of industrial workers but also for designing controls requiring high force. This paper presents a comparison between maximal static handbrake pulling force (FST) and force exerted during normal handbrake pulling task (FDY). These forces were measured for different handle locations and subject characteristics. Participants were asked to pull a handbrake on an adjustable car mock-up as they would do when parking their own car, then to exert a force as high as possible on the pulled handbrake. Hand pulling forces were measured using a six-axes force sensor. 5 fixed handbrake positions were tested as well as a neutral handbrake position defined by the subject. FST and FDY were significantly correlated. Both were found to be dependent on handbrake position, age and gender. As expected, women and older subjects exerted lower forces. FST was significantly higher than FDY. The ratio FmR (FDY divided by FST) was also analyzed. Women showed higher FmR than men meaning that the task required a higher amount of muscle capability for women. FmR was also influenced by handbrake location. These data will be useful for handbrake design. PMID- 22316899 TI - Movement strategy and performance in a high-volume order picking workstation. AB - The design of a work station generally prescribes a global movement pattern of the operator, but also leaving some degrees of freedom regarding movement strategy. For a specific order picking work station, we studied the movement strategies, the underlying factors and its impact on performance. Eight subjects performed a task comprising, the picking and placing of an object and pressing a button in eight conditions varying in product weight, movement direction (left vs. right), and placing distance. Movements were analyzed and cycle times were obtained from video-recordings. We observed various types of strategy regarding hand use and global placing mode (reaching vs. placing). The different strategies did not show clear relationships with performance (in contrast to the various work place factors). Ergonomically spoken, the fact that the workstation allows movement variation without loss of performance, is favorable. PMID- 22316900 TI - A study of the kinematics of ingress and egress of upright and recumbent seats. AB - Research has been done on the maximum reach and ingress/egress of upright seats. However, research on recumbent seats and comparisons between recumbent and upright seats is limited. By using an eight-camera Vicon motion capture system and C-motion Visual 3D modeling software, this research compared the ingress/egress joint kinematics and maximal planar reach of an upright seat with a recumbent seat. Mean range of motion and mean peak angle for each ingress/egress task were determined and the values for the upright seat were compared to the values for the recumbent seat. For each reach task, three extreme points were extracted and compared between the upright and recumbent seat. Seat orientation was found to have a statistically significant effect on the range of motion of several joints during the ingress/egress tasks, as well as one of the extreme points during the reaching tasks. PMID- 22316901 TI - Ergonomics and design in a ischial support proposal for the Medellin metro, Colombia. AB - This project, developed by the Design Studies Research Group at the Universidad Pontificia Bolivariana (UPB), presents a design proposal focused on human factors for ischial support for the stations of the Medellin Metro. An initial pilot scheme was developed on Platform 'A' of San Antonio - the most important transfer station. The methodology of the Ergonomics Research Division at UPB constituted the basis of the project. This methodology observes, analyses and draws conclusions of the conditions that optimize the User-Product-Context nexus, and in doing so defines design requirements which, in this proposal, centered on the needs of the users of the Medellin Metro. The Experimental Morphology Research Division provided technical support in the form of modelling, production and structural testing of the object. The proposal includes thematic units, themes and priority components for analysis and application in the design process. In addition, the project generates certain activities and moments that future designers can develop in a parallel manner, coherent with the vision of ergonomics. The methodology focused on the requirements of the users and took into account the existing space (the Metro System), thus establishing relationships of use that were coherent with the principles of ergonomics and design. PMID- 22316902 TI - Ergonomic design intervention strategy for work tools development for women agro based workers in Northeast India. AB - Strategy for finding the appropriate strategy for work tool development has become a crucial issue in occupational wellness of varied nature of women workforce of Northeast India. This paper deals with ergonomics intervention through sustainable work tool design development process. Workers who frequently shift to different activities quite often in unorganised small-scale fruit processing units where productivity is directly related to the harvesting season require different work tools relevant to specific tasks and mostly workers themselves manage work tools of their own with available local resources. Whereas in contrast the tea-leaf pluckers are engaged in a single task throughout the year, and the work schedule and work equipment is decided and supplied to them based on the corporate decision where the workers do not have any individual control. Observations confirm the need for organising participatory workshops specific to trade based occupational well-being and different work tools for different tasks in mostly private owned unorganised sector. Implementation of single variety work tool development that supports a crucial component in tea leaf plucking for which they are engaged in full time employment; and through a corporate decision a single design with its number of users makes a good effect. PMID- 22316903 TI - An ergonomic approach to design hand tool for agricultural production. AB - Hand tool mechanisms designed to reduce the risk factors have rarely been studied. In this paper it is analyze trowel firstly designing in CATIA and then its Finite Element Analysis has been carried out by ABAQUS. The main emphasis is on finding stresses by using this software, then removing them by suitable mechanical working on tool & ergonomic change in the design of handle to make it more comfortable. Body part discomfort score and overall discomfort rating experienced by the subjects had also been estimated. During the muscular activity workers physiological responses i.e. energy expenditure rate, oxygen consumption rate and heart rate increases. This increase in physiological responses is related to the type, intensity and duration of work and thus sets limits to the performance of heavy work. In this paper oxygen consumption rate and heart rate was used for physiological cost estimation. These parameters were measured by Computerized Ambulatory Metabolic Measurement System K4b2. PMID- 22316904 TI - A field experiment comparing mechanical demands of two pruners for flower cutting. AB - Manual flower cutting requires repetitive forceful movements that may explain the high incidence of upper-extremity MSDs among workers of the Colombian flower industry. Force demands may be caused by the use of pruners that have not been designed for Colombian workers. We conducted a repeated measures field experimental study (n=16, 69% women, 20 to 60 years old) to compare the mechanical demands during rose cutting of two different pruners (Traditional vs. alternative pruner) at two different cutting heights (elbow vs. over-shoulder). Demands included the perceived comfort, perceived effort and upper limb's muscular activity and posture. Workers perceived their traditional pruner as more comfortable but requiring more effort than the prototype tool. No benefits were observed regarding ulnar deviation with the alternative pruner. The wrist extension and related muscular activity of the wrist extensors were higher with the prototype pruner. The prototype pruner resulted in reduced muscular load of the wrist flexors; the biceps when working at the elbow height; and the deltoids when working at the shoulder height. However, Moderate results may be explained by the lack of time for workers' adaptation to the alternative tool. New design developments must focus on reducing extension and ulnar deviation of the wrist. PMID- 22316905 TI - Openability of soft drinks PET packagings. AB - Studies on packaging accessibility are still incipient in Brazil. Many of these packagings can represent a challenge to users, whether due to non-informative labels, tricky tabs or seals, or even those that need strength to open. This paper brings a simple test to determine the necessary torque force to open PET bottles, and to predict the amount of users that could not open it. The findings suggest that a considerable amount of users could not open it or would have some difficulties to exert the necessary force. PMID- 22316906 TI - The use of thermal manikin to evaluate interface pressure distribution. AB - The use of a thermal buttocks manikin was explored as a tool to standardize the evaluation of seat comfort. Thermal manikin buttocks were developed and calibrated thermally and anatomically to simulate the sensible heat transfer of a seated person and used to evaluate interface pressure distribution. In essence, the pressure maps of manikin buttocks with and without heating were compared to those of a seated person. The results of average pressure demonstrated that the thermal manikins have a better response in interface pressure measurement than manikins without heating. PMID- 22316907 TI - The hierarchy of needs to inclusive design. AB - This paper focuses Design importance in the development of effectively inclusive products based on Design Emotional approach, allowing children with disabilities to experience playing in the childhood as an instrument for social integration. The methodology used to develop this study was based on literature review, considering the following themes: emotional design, accessibility and inclusion, emotion and development of children. As a result, we propose a new level of need to model the hierarchy of needs, of Jordan ("usability", "functionality" and "pleasure"), level with the inclusion of "dignity." PMID- 22316908 TI - Designing from activities. The "ability /difficulty table", a useful tool to detect the "limit users" in the Design for All Approach. AB - In the Design for All Approach (DfA), an important phase of the design process consists in the individuation of the so-called "limit users", that are that particular group of people with the most "critical" features for the autonomous fruition of a system or a product. Generally, however, it is not easy to identify them in a complete and objective way. A clear and complete outline of design requirements with respect to the "normal" use of a service, product or environment, moreover, is of fundamental importance in inclusive design. In fact, we know how bad design, that doesn't take in account the true "strategies of use", may lead to situations of handicap, also serious, temporary or permanent, regardless if the user is a "disabled" person or not. In relation to this scenario, the paper shows the results of a research which has developed the "Ability/Difficulty Table" ("A/D Table"), a new tool useful to identify the so called "limit users" and their needs with respect to different activities, linking the main "difficulties", expressed by people, with the "abilities" required to carry out in autonomy the investigated activity. PMID- 22316909 TI - "EWS Matrix" and "EWG Matrix": "De-sign for All" tools referred to the development of a enabling communication system for public spaces. AB - The widespread sense of spatial disorientation that can be experienced in many public places (buildings and open spaces),generally depends on a design approach that doesn't take into account both the "communication skills" of the different parts of the spatial organization, both the variability of people and their ways of interacting with environments, orienteering themselves. Nevertheless, "not find the way" often has some obvious practical costs (loss of time, failure to achieve a target) and some more intangible, but no less important, emotional costs. That's why the design of signage systems must take into account both the specificities of places and the extreme variability of its users. The paper presents the results of a study on this specific issue. In particular, the study focuses on the description of some tools useful for the analysis and design of a signage system that is truly "for All". PMID- 22316910 TI - Ergonomics and design for all. AB - The paper deals with research areas and actions thanks to which the theoretical and methodological content of the "Ergonomics in Design" project can give a concrete contribution to the "Design for All" project, in particular with regards to the assessment and design of environments, the design of everyday products. PMID- 22316911 TI - The user testing toolset: a decision support system to aid the evaluation of assistive technology products. AB - Developers of assistive technology products need to ensure that their offerings meet the requirements of end users, and that usability issues have been discovered prior to manufacture. This may be difficult for SMEs (Small Medium Enterprises) who may lack the necessary skills and resources required to plan and conduct an evaluation. To assist SMEs in the assistive technology market, a stand alone, decision support system was developed to assist in the planning and evaluation of their products, taking into account the resources available, nature of the product being developed and stage of the design process. The responses given by the designer to 40 multiple choice questions are matched against a database of 42 research methods. The methods achieving the highest score in relation to all questions are displayed as the final output. The paper describes the development of the User Testing Toolset (UTT), including the additional functionality provided to ensure that the evaluation methods were correctly matched and weighted to the responses. PMID- 22316912 TI - Auxiliary locomotion device to unload lower limbs, using user's own secondary support. AB - The systematic of device development for support in the period after surgery and for consolidation of fractures of lower limb, manufactured in aluminium alloy and PVC, integrated with quick fixes, cleanliness simplified, retractable, and adaptable to wide range of biotope. Has as value-added a possibility of transforming an axillary crutch in Canadian and, where necessary, the transformation of the Canadian crutch in cane to aid the balance and safety on return to walk independently. The proposed instrument enhances the limited movement capabilities and mobility by ensuring greater security and versatility of the beginning of the user's recovery until the end of his convalescence. PMID- 22316913 TI - A conceptual model for barrier free facilities planning. AB - This paper presents the proposal of a model for planning a barrier free industrial facilities, considering the demands that inclusion requires, ranging from outside the factory (social environment), to the needs of the production system and the workstation. Along with literature review, the demands were identified in a shoe manufacturer that employs people with disabilities, and organized taxonomically in agreement with the structure for planning facilities. The results show that the problems are not primarily related to eliminating architectural barriers and factors aimed at preventing risks to people's health and safety but, rather, are related to the company's cultural environment, because the main hazards are managerial. In special cases, it is suggested there is a need to adjust those parts of tasks that the worker cannot do, or even to re schedule work so as to make it possible for employees with disabilities to perform their tasks. PMID- 22316914 TI - Ergonomics issues in conceiving an accessible project. AB - Public space is endowed with undeniable social relevance, thus becoming a defining element of integration and interaction among its users. Aware of this importance the Universidade Federal da Paraiba (UFPB), linked to the Ministerio da Educacao e Cultura (MEC), develops the project "UFPB para todos: eliminando barreiras'' (UFPB for all: removing barriers) that aims to conceive an architectural design of an accessible rout to UFPB's campus I, and execute a pilot stretch of this route. This article aims to subsidize the preprojectual phase by understanding the needs of this campus' users, through the concepts of ergonomics and universal design. Was performed out direct observation of the space, and the methods of interviews and observation of user behavior were applied to a group of students with disabilities, through the techniques of assisted walking, photographic and video recording. Based on those, projective guidelines have been defined, which will contribute to the final project's quality, so that this is not a simple application of the rule, but works free of segregating barriers. PMID- 22316915 TI - Minimum housing spaces, flexibility and sustainability: a reflection on the basis of ergonomics intervention. AB - This article discusses the quality of internal life space in apartments of residential buildings in the northeast region of Brazil, especially the possibility to adapt environments with small areas (according to local building codes) to the needs of different arrangements of families (considering 4 members per family). The research had a gradual approach and used multimethod strategy: (a) studying the universe of residential buildings whose apartment's inner area is between 50 and 60 m2 and were constructed in Natal-RN between 1998 and 2008, as well as not linked to social housing programs and occupied for more than one year; (b) selecting a building to do a Post Occupation Evaluation (POE), using walkthrough, technical observation and questionnaires; (c) choosing of two housing units to do an ergonomic intervention (based in interviews and detailed measurements). The results show the technical possibility to modify the units, but these modifications have a high (social, economic and environmental) price, because in general the space of units projected is not flexible. So, the paper concludes that this type of enterprise needs to be rethought, since part of them is (social and ecologically) unsustainable. PMID- 22316916 TI - Ergonomics and accessibility for people with visual impairment in hotels. AB - This article presents a diagnosis of luxury or superior hotels in the city of Natal, located in the state of Rio Grande do Norte, in northeastern Brazil, in what concerns accessibility to the visually impaired. The main objective is to present the guiding principles to design actions and interventions that must be considered in the preparation or revision of technical standards and manuals of good practice in accessibility related to people with visual impairments who are hotel users. The survey showed that the hotels do not meet the normative indications of accessibility, their facilities are in-accessible (have prevented access) or of reduced accessibility and its employees are not prepared to provide adequate hospital services for people with visual impairment. It was concluded that some of the accessibility problems faced by people with visual impairments are also faced by people in general. PMID- 22316917 TI - Change of the layout of an office of a metallurgical company: simple projects, big solutions. AB - The posture, a good organization and the proper layout of the environment and workplaces have a positive influence on the income of an employee. To develop the work it is used a methodology that addressed the study phases of the theory involving the subject, description of the current situation, preparation of conceptions, choice of design, implementation and reporting of results. Through the project of "Change of the layout of an office of a metallurgical company" there was an intervention in these reported aspects providing improvements in the office, regarding ergonomic, layout, workplace and lighting issues, bringing welfare to the official, with the intent to improve its performance within the company and facilitating its actions, as the company's customer service. The results provided improvements in layout, in the workplace and especially in comfort for the human resources that perform their activities. PMID- 22316918 TI - Workplace aesthetics: impact of environments upon employee health as compared to ergonomics. AB - Associations between self-reported needs for aesthetic and ergonomic improvements were studied to analyse a possible impact of aesthetic needs on job performance as compared to ergonomic needs in 11 occupational groups. Employees at Swedish broadcasting company were invited to participate in a cross sectional study. 74% (n=1961/2641) fulfilled the inclusion criteria. Demographic data from company files and a pre-validated questionnaire were used. 'High rank' and 'low rank' aesthetic and ergonomic needs were compared. The perceived needs for aesthetic and ergonomic improvements showed significantly different distributions (p<0.001). Aesthetic needs were more frequently reported. No gender related differences were observed. Differences between occupational groups were shown (p=0.006, 0.003).'High rank' needs for aesthetic and ergonomic improvements were similarly associated to psychological demands, stress, pain and age. 16/24 factors showed significant differences between 'high and low rank' aesthetic needs, whereas 21/24 between ergonomic needs. Sick leave was stronger related to ergonomics. The study results show a relation between not only work place ergonomics but also work place aesthetics to health and well-being. Future work health promotion and prevention may benefit from the inclusion of workplace aesthetics. PMID- 22316919 TI - Usability requirements for buildings: a case study on primary schools. AB - This paper concerns an applied research aimed at applying the concept of usability, as derived form the standard ISO 9241/11, in the filed of building design, namely primary schools. Starting from the concept that space characteristics play a very relevant role in learning performances, the study presented here developed an original methodology for the assessment of effectiveness, efficiency and satisfaction of buildings hosting primary schools, in order to create a school environment better supporting users in their tasks. Research core is the framework of usability requirements and their related markers, indicators and technical specification that has been formulated in order to check compliance of urban area, building, rooms and architectural details with users needs. Therefore, a detailed task analysis of pupils and teacher tasks has been carried out and two questionnaires addressed to a significant users panel have been formulated for satisfaction survey. Lastly, a matrix for an overall reading of gathered data has been set-up and criteria for usability assessment based on that data has been defined. The whole study has been developed within the case study of a primary school in the Naples city centre, whose contents and results are discussed. PMID- 22316920 TI - Ergonomic evaluation of the environment: a case study in a control room of the hydroelectric sector. AB - Representative systematic evaluation studies of the workspace and the extent to which that space is suitable for performing tasks have been developed by professionals engaged on finding evidence as to the importance of users and designers being joint participants in drawing up projects. In this context, this paper sets out to evaluate the environment of a control room in the hydroelectric sector, based on a multidisciplinary method which integrates ergonomics, architecture and environmental psychology so as to assess the influence of space on the user, and thus to identify the user's level of satisfaction with it. It was observed that some adaptation strategies of the space for activities were not implemented satisfactorily, resulting in the need for further studies on making workspaces suitable. PMID- 22316921 TI - Evaluating attributes concepts for build environment. AB - Based on semi-structured interviews answered by professionals in Architecture and Interior Design areas, this research aimed to investigate, how these professionals develop their projects. Considering a real situation, the research tried to find out how these professionals consider users necessities and opinions. It was also verified which attributes are considered most relevant and how these professionals correlate them to uses demands about ergonomic aspects and intrinsic characteristics of each project. The paper is concluded presenting a list of attributes that were identified as the most important when developing a design for a home kitchen (as example), and some considerations about this topic are also presented. PMID- 22316922 TI - Development of objective discomfort evaluation indicators for a task-oriented motion using less constrained motion concept: application to automotive pedal clutching task. AB - This paper presents a method to develop objective discomfort evaluation indicators for a task oriented motion using the concept of less constrained movement. The basic idea is to compare imposed and less constrained movements in order to identify relevant biomechanical parameters for defining objective discomfort indicators. The task of automotive pedal clutching was chosen for illustrating the proposed method. Based on discomfort questionnaire and motion analysis of the experimental data, four discomfort indicators were proposed. Two of them were based on the ankle joint angle around flexion/extension axis at the beginning and the end of the clutch pedal depression. The third one was defined using knee flexion/extension joint torque at the end of the clutch pedal depression. The last indicator was defined as the relative lateral position of the heel compared to the average pedal lateral position for less constrained configurations. A global discomfort function was also defined as a weighted sum of all indicators. Globally, the proposed global discomfort indicator succeeded in differentiating the tested configurations in agreement with experimental observation. As expected, less discomfort rating is obtained for less constrained movement when compared with the corresponding imposed one. PMID- 22316923 TI - Three experiments to support the design of lightweight comfortable vehicle seats. AB - Seats need to be more lightweight for airplanes, cars, busses and even trains to contribute to a better environment and to reduce energy consumption. However, a reduction in comfort due to weight reduction is not preferable, which opens a new area of research: improving comfort with a minimum of material or with lightweight materials and systems. In this paper three experiments are performed to test the effects of light weight seats and parts of a seat on comfort. The first experiment shows that a new developed light weight massage system improves comfort and reduces muscle activity. The second experiment shows that the automatic seat adjustment without motors improves the comfort as well. The third experiment showed that a light weight seat following closely the human body contour is experienced on many aspects in the same way as current more heavy seats. More research and models will be needed in this ergonomic field which needs more attention. PMID- 22316924 TI - Multi-platform experiment to cross a boundary between laboratory and real situational studies: experimental discussion of cross-situational consistency of driving behaviors. AB - We constructed an innovative experimental platform to study cross-situational consistency in driving behavior, conducted behavioral experiments, and reported the data obtained in the experiment. To discuss cross-situational consistency, we separated situations in which people use some systems to conduct tasks into three independent conceptual factors: environment, context, and system. We report the experimental results with the following systems: a laboratory system with a gaming controller and steering/pedal controllers and a real system, COMS an instrumented vehicle. The results are summarized as follows. 1) The individual behaviors in each system were stable, and consistency was retained. 2) The consistency of the behaviors was also confirmed when the participants drove using different interfaces in identical systems. 3) However, only slight correlation was observed across different systems in a specific situation where a strong high order cognitive constraint (i.e., rapid driving) and a weak low-order cognitive constraint (driving with easy handling toward a straight-line course) were given. PMID- 22316925 TI - Ergonomic evaluation of interior design of Shoka vehicle and proposing recommendations for improvement. AB - One of the applications of ergonomics disciplinary is designing driver workstation compatible to users' characteristics. The aim of this study was evaluation of interior design of Shoka vehicle with respect to the accommodation for Iranian population and proposing suggestions for customizing design of this vehicle. This study was a descriptive-analytical study conducted among thirty men from Iranian drivers population in 5, 50, 95 percentiles of the stature variable. Objective variables related to the occupant packaging and vehicle visual aspects including anthropometric variables, frontal, lateral, and side view and so on were investigated first. Then, subjective variables related to the driver mental workload and body comfort discomfort were studied using BMDMW and comfort questionnaires during 2-hour driving trial sessions. Occupant packaging variables and hand-arm angle showed the least accommodation percent (%53). Seating angles showed low accommodation as well (%73). Among three percentile groups there were no significant differences between the mean values of mental workload during two hours driving task. And, the mean value related to the comfort discomfort was 3.9 during driving sessions. Considering the findings in this study, it can be conclude that seating angles need correction and optimization. Taking mental workload results into account, it can be concluded that the interior design of the studied car had no influence on drivers' mental workload. From the aspect of comfort discomfort, Shoka vehicle showed neutral state among drivers. Optimizing seating angles, decreasing vibration, correcting stiffness of seating pan are suggested for customization of the ergonomics aspect of this vehicle. PMID- 22316926 TI - Adoption of ergonomic features in a new reach truck cabin design--a usability study. AB - The task of handling reach trucks frequently involves poor working postures. The location of the steering wheel in most reach trucks is in front of the operator which requires the drivers to bend forward and stretch their hands for holding onto the steering wheel. To overcome visibility restrictions, this posture is aggravated by twisting and bending their torso sideways. This paper presents a usability study which was conducted to compare adoption of ergonomic features in a new reach truck cabin with the way they were intended to be employed for improving physical working conditions. Participants drove the reach truck on a test track performing tasks of varying complexity. Video recordings were utilized to facilitate the observations. The results indicate that improved ergonomics features of the reach truck are not used as intended. The test subjects instead adopted postures that they were accustomed to when driving common reach trucks. The possible contributing factors to this posture regression are discussed. The procedure used in this study is recommended for the companies to determine the effectiveness and adoption of ergonomics solutions. PMID- 22316927 TI - Experimenting new design languages in contemporary home design. AB - The changes in society at the beginning of this millennium are giving rise to deep transformations in the behavioural trends and tastes of home users, as well as in their lifestyles and consumption patterns. This opens up a wide range of opportunities for innovation within the context of contemporary home design. Due to the emergence of new user profiles, new needs and models are coming to the attention of designers and manufacturing companies. Just think about the new needs resulting from the changing composition of households, new forms of cohabitation and the contemporary multi-ethnic society. PMID- 22316928 TI - The Intermodal Bike: multi-modal integration of cycling mobility through product and process innovations in bicycle design. AB - The paper presents the early results of the UE-FP7 project "The Intermodal Bike". The research aim is to provide a super-compactable, super-lightweight folding bicycle as a realistic solution to graft the cycling mode onto the root of the public or private transportation systems. The folding bikes now on the international market reach weighs between 12-15 kg, with a variable footprint but occupying -when compacted- an average volume of about 100 liters. To encourage the use of this vehicle and to extend it to a larger number of users with different characteristics, the research project has set its goal in increasing as possible compactness and light weight, creating a bicycle with a volume when compacted of 20 liters (reduction factor =5), with a shape of 48 * 36 * 12 cm and a weight of 5 kg. max., ensuring stability and improving vehicle usability and efficiency, during the ride and in the phase of bike folding. To achieve this goal ergonomic and usability tests have been carried out. The tests allowed to find a posture that would ensure efficiency and comfort in the ride to as many users as possible. Parallel tests were made on the vehicle usability in the urban transport system and intermodal. The need for light weight has required special studies on the optimization of the vehicle's architecture and research on super lightweight materials. PMID- 22316929 TI - Ergonomic and usability analysis on a sample of automobile dashboards. AB - This is a research study based on an analysis which sets out to identify and pinpoint ergonomic and usability problems found in a sample of automobile dashboards. The sample consisted of three dashboards, of three different makes and characterized as being a popular model, an average model and a luxury model. The examination was conducted by observation, with the aid of photography, notes and open interview, questionnaires and performing tasks with users, the bases of which are on the principles laid down by methodologies. From this it was possible to point to the existence of problems such as: complaints about the layout, lighting, colors, available area, difficult access to points of interaction, such as buttons, and the difficult nomenclature of dials. Later, the findings and recommendations presented show the need for a further, deeper study, using more accurate tools, a larger sample of users, and an anthropometric study focused on the dashboard, since reading and understanding it have to be done quickly and accurately, and that more attention be given to the study of automobile dashboards, particularly in the most popular vehicles in order to maintain the standards of usability, and drivers' comfort and safety. PMID- 22316930 TI - Towards the application of interaction design to digital TV content development. AB - Television can be considered one of the main means of mass entertainment. It occupies an important place in people's lives, influencing behavior and creating and/or enforcing consumer's habits and needs. With the advent of Digital Television, a series of new features tend to further impact upon society in many different ways. The main agent of this change is interactivity, which is the leverage that will transform the traditional viewer's role. Interactivity turns the viewer into a user, a partner who receives the content, but also produces, participates and collaborates during the viewing process. This paper aims to discuss the importance of applying interaction design in the development of projects related to digital television. The main factors that may contribute to improve the interaction design in applications for digital TV were identified drawing on a descriptive and qualitative method of investigation. The results showed that the interface design for this new media should not only be aesthetically appealing, but should also focus on usability (i.e. user's wishes and needs). Additionally, the creation of these interfaces requires the investigation of some characteristics and limitations of device interaction, considering the choice of colors, saturation levels and brightness, avoiding graphic symbols and prioritizing the navigation through the numerical buttons of the remote control. PMID- 22316931 TI - Interface design and contemporary: human creating new guidelines for high-tech products. AB - Contemporary electronic industry offers a wide range of products. Usually touch sensitive and with few buttons and a lot of functions these products not always have a friendly interface. The human x design interface based on electronics' ergonomics is the focus of this research. An evolutionary analysis of the electronics industry design within a contemporary context clarifies this relation and proposes new guidelines for a more conscious design. PMID- 22316932 TI - An ergonomic study on the navigation structure and information units of websites with multimedia content. A case study of the Xbox 360 promotional website. AB - This paper presents an ergonomic study on the navigation structures and information units of entertainment sites with multimedia content. This research is a case study on the XBOX 360 promotional website. It analyzes the presentation of the content on a grid that simulates the spatial displacement of the screen's elements and evaluates the interaction that the page allows for, from the users' point of view. PMID- 22316933 TI - Urban ergonomics: an ongoing study of city signs and maps. AB - The purpose of this study is to assess whether the existing signals in three European cities were developed according usability principles and ergonomic aspects for the citizen. City maps and signals will be tested using efficiency, effectiveness and user's satisfaction criteria. Among the urban areas are the center of Paris-FR, assumed to be well signalized, the historical center of Guimaraes-PT and Chorweiler, Cologne-DE, a residential neighborhood of modern urbanism characterized by the extensive use of vegetation, the landscape homogeneity, and, consequently, by the difficult navigation. PMID- 22316934 TI - Ergonomics and design: traffic sign and street name sign. AB - This work proposes a design methodology using ergonomics and anthropometry concepts applied to traffic sign and street name sign projects. Initially, a literature revision on cognitive ergonomics and anthropometry is performed. Several authors and their design methodologies are analyzed and the aspects to be considered in projects of traffic and street name signs are selected and other specific aspects are proposed for the design methodology. A case study of the signs of "Street of Antiques" in Porto Alegre city is presented. To do that, interviews with the population are made to evaluate the current situation of signs. After that, a new sign proposal with virtual prototyping is done using the developed methodology. The results obtained with new interviews about the proposal show the user satisfaction and the importance of cognitive ergonomics to development of this type of urban furniture. PMID- 22316935 TI - A brief essay on ergonomics in graphic design. AB - Through Brazilian publication revision on the relations amongst Ergonomics and Design, we observed the tendency towards an approach focusing on product design. However, it is our duty to question which would be the influences of ergonomics in the graphic design. As a methodology, we considered the identification that the practices derived from ergonomics as epistemic system found in the main bibliography related to graphic design. PMID- 22316936 TI - Informational ergonomics and design: signage design for Monte Siao Camp. AB - This paper refers to the development of a signage system, driven by the vector of Signage Design and Informational Ergonomics associated with Regulatory Standards. The methodology of the Ergonomic Intervention of Moraes and Mont'Alvao (2003), in its early stages, and the Method of the Signage Pyramid of Calori (2007) were used to develop the research, data collection and analysis and to guide the design by a signaling system. The system contemplated by this job is called Mount Zion, a site of 19 hectares, which has signs of disturbance. As a result, we obtained a signaling system, with graphic features that refer to formal-site, capable of meeting the needs of orientation and displacement inherent to the site. PMID- 22316937 TI - Analyzing Web pages visual scanpaths: between and within tasks variability. AB - In this paper, we propose a new method for comparing scanpaths in a bottom-up approach, and a test of the scanpath theory. To do so, we conducted a laboratory experiment in which 113 participants were invited to accomplish a set of tasks on two different websites. For each site, they had to perform two tasks that had to be repeated ounce. The data were analyzed using a procedure similar to the one used by Duchowski et al. [8]. The first step was to automatically identify, then label, AOIs with the mean-shift clustering procedure [19]. Then, scanpaths were compared two by two with a modified version of the string-edit method, which take into account the order of AOIs visualizations [2]. Our results show that scanpaths variability between tasks but within participants seems to be lower than the variability within task for a given participant. In other words participants seem to be more coherent when they perform different tasks, than when they repeat the same tasks. In addition, participants view more of the same AOI when they perform a different task on the same Web page than when they repeated the same task. These results are quite different from what predicts the scanpath theory. PMID- 22316938 TI - Web accessibility: evaluation of a website with different semi-automatic evaluation tools. AB - It is essential that access to information must to be universal given the importance of having a truly global Internet. This study proposes to evaluate a government website with two semiautomatic accessibility evaluation tools. The results have demonstrated that the use of more than one semi-automatic assessment tool can provide enhanced results. The differences in results and presentation in the reports generated by the two tools indicate that there is more complete results by combining tests with different accessibility evaluation tools. PMID- 22316939 TI - The effect of job rotation intervals on muscle fatigue--lactic acid. AB - This study is a job rotation comparative that aims to define the properly scheme to be in use at the time it is performed. As fatigue plays directly against the work results this comprehensive study about the action of lactic acid over workers at different jobs and strength demand was realized to find the best methodology to maximize those rotations. PMID- 22316940 TI - Members of the human body prone to musculoskeletal damages: a comparison between the sector of transportation and footwears production. AB - This study present areas of the body more prone to develop diseases by musculoskeletal efforts, ie, RTD, in two companies of Paraiba, Brazil. To this end, was made a comparative analysis with respect to the type of work performed (standing, sitting) and the parts that suffer most discomfort after a day's work in a footwear industry and a bus transportation company. The quanti-qualitative research was conducted through semi-structured interviews with 227 employees in the period 2008 to 2009, having as methodological the tool diagram of painful areas of Corlett and Manenica. It was concluded that the areas most affected by musculoskeletal disorders are located in the neck (9,2%), backs (23,6%), shoulders (14,5%) and legs (11,3%), being usually caused by inappropriate postures, repetitive movements and work station no adequate the anthropometry of the users. Thus, we recommend the adoption of ergonomic measures that enable a healthy and safe environment for workers. PMID- 22316941 TI - Impact of hand forces and start/stop frequency on physiological responses to three forms of pushing and pulling: a South African perspective. AB - There has been limited attention given to the physiological demands of pushing and pulling, especially in industrially developing countries such as South Africa. Two key factors affecting the physiological demands of these tasks are the hand forces exerted and the start/stop frequency. The purpose of the current study was therefore to investigate the physiological responses to pushing and pulling at various loads and start/stop frequencies. 36 male subjects participated in the study and were required to complete a total of 18 conditions (three techniques: pushing, two- and one-handed pulling; three loads: 200, 350 and 500 kg; and two frequencies: 2 and 4 stops per minute). During each condition the heart rate, oxygen uptake and energy expenditure were measured. Pushing was found to elicit significantly lower responses for all three dependent variables than either form of pulling. The start/stop frequency was also found to have a significant impact on subject responses. The findings of this study indicate that the technique adopted to maneuver loads is critical in determining the physical demands placed on the human operator. Furthermore increasing the frequency of start/stops plays an important role, thus the forces exerted during these two phases are important from a physiological perspective. PMID- 22316942 TI - Needs of ergonomic design at control units in production industries. AB - During the last decades, an increasing use of innovative technologies in manufacturing areas was monitored. A huge amount of physical workload was replaced by the change from conventional machine tools to computer-controlled units. CNC systems spread in current production processes. Because of this, machine operators today mostly have an observational function. This caused increasing of static work (e.g., standing, sitting) and cognitive demands (e.g., process observation). Machine operators have a high responsibility, because mistakes may lead to human injuries as well as to product losses - and in consequence may lead to high monetary losses (for the company) as well. Being usable often means for a CNC machine being efficient. An intuitive usability and an ergonomic organization of CNC workplaces can be an essential basis to reduce the risk of failures in operation as well as physical complaints (e.g. pain or diseases because of bad body posture during work). In contrast to conventional machines, CNC machines are equipped both with hardware and software. An intuitive and clear-sighted operating of CNC systems is a requirement for quick learning of new systems. Within this study, a survey was carried out among trainees learning the operation of CNC machines. PMID- 22316943 TI - Cognitive ergonomics: the use of mind mapping tool in maintaining productive sector of a Brazilian paper company. AB - The use of mind maps as a method of building knowledge, planning, organizing activities and ideas can be seen in the literature related to ergonomics. The results of such use are relevant and its use in academic area found. However, regarding to its use in industrial environments, studies can't not be found. With this scenario, and based on the perception of the ergonomist about the importance of using methods such as mind maps in support of human cognition, it seems pertinent to its use in industry sectors whose cognitive demand requires. Given these assumptions, this study aimed to apply the method of Mind Maps in Productive Maintenance sector of a Brazilian paper. The Productive Maintenance sector in the Paper Industry has an important contribution to operational performance. With practical Predictive Maintenance, Preventive Maintenance and Corrective Maintenance, the industry advocates to make the machines to produce paper is not to stop producing when they are programmed to do so. Among the practices cited, the Preventive Maintenance is one that leads to pre-determined intervals in order to reduce the possibility of placing the equipment in a condition below the required level of acceptance. Therefore, this article aims to propose using the tool "mental maps" in order to collaborate in planning and implementation of preventive maintenance activities in the sector of mechanical maintenance of a pulp and paper industry in southern Brazil. The study investigated the maintenance sector through its employees, who went through training about the tool and then use it and ergonomists company. PMID- 22316944 TI - Analysis of the thermal comfort model in an environment of metal mechanical branch. AB - This study aims to identify the correlation between the Predicted Mean Vote (PMV) with the thermal sensation (S) of 55 employees, establishing a linear multiple regression equation. The measurement of environmental variables followed established standards. The survey was conducted in a metal industry located in Ponta Grossa of the State of Parana in Brazil. It was applied the physical model of thermal comfort to the environmental variables and also to the subjective data on the thermal sensations of employees. The survey was conducted from May to November, 2010, with 48 measurements. This study will serve as the basis for a dissertation consisting of 72 measurements. PMID- 22316945 TI - Ergonomic analysis in cold storage rooms: a study of case. AB - The human work possess a history and, in this dimension, the man is submitted to the conditions that confer it physical and psychological consequences. The activity of work in the present time imposes adverse labor conditions. The ergonomics is a science that it aims at to study the real activity of the work with sights its transformation. This study it was carried through in a sector of processing of meats in a Agroindustry, with the objective to analyze ergonomically the conditions of work and the possible risks it greets it of the workers. It was verified that in the accomplishment of the activities it had an overload of the musculature of superior members, where if it verified the requirement of repetitive movements during four working hours. Also observed the organization of the work, the position of the employees and way to carry through the activities. With the study we conclude that the ergonomic risks in the sector are related to the position during the accomplishment of the activities, requirement of repetitive movements, e the cold that affects the muscular control, reducing some motor abilities as the dexterity and the force. PMID- 22316946 TI - Implementation of an ergonomics program for the welding department inside a car assembly company. AB - The premise for this project is to implement an ergonomics program for the welding department of a car assembly company, considering that this area represents the highest occupational risk in relation to musculoskeletal injuries. The project also allows the demonstration of the different implementation processes of an ergonomics program; it also permits the determination of individual risks faced by workers of the welding department, and finally gives a chance of improving common injuries using the sentinel system. The main challenge is to reduce musculoskeletal injuries and absenteeism among welders through actions implemented by the ergonomics program. PMID- 22316947 TI - Successful integration of ergonomics into continuous improvement initiatives. AB - Process improvement initiatives are receiving renewed attention by large corporations as they attempt to reduce manufacturing costs and stay competitive in the global marketplace. These initiatives include 5S, Six Sigma, and Lean. These programs often take up a large amount of available time and budget resources. More often than not, existing ergonomics processes are considered separate initiatives by upper management and struggle to gain a seat at the table. To effectively maintain their programs, ergonomics program managers need to overcome those obstacles and demonstrate how ergonomics initiatives are a natural fit with continuous improvement philosophies. PMID- 22316948 TI - Investigating the effects of physical and cognitive demands on the quality of performance under different pacing levels. AB - The study was undertaken to investigate the effects of pacing on aspects of performance at an assembly task and on the operators' responses related to work behaviour, perceived workload and perceived stress. A particular objective of the study was to investigate whether physical and cognitive demands may interact in their influences on these effects. An assembly task was simulated in the laboratory and the level of pacing imposed, work height and memory load within the task were all varied. The results showed that the type of pacing commonly imposed (as is common with a lean manufacturing Takt time system in industry) can significantly affect both performance and perceived workload and stress. Physical demands (through work height affecting posture) and mental demand (through memory load) were also found to have significant effects, as would be expected from the many studies of these in the literature. More importantly, some interactions were found between pacing and work height in their effects on quality of assembly and the operator's own rating of performance, and between work height and memory load in their effects on errors. These findings will need to be taken into account by companies when implementing Takt time systems. PMID- 22316949 TI - DMAICR in an ergonomic risks analysis. AB - The DMAICR problem-solving methodology is used throughout this paper to show you how to implement ergonomics recommendations. The DMAICR method consists of the following five six steps by which you can solve ergonomic design problems: The steps of the proposed method, adapting DMAICR, are the following: In the steep D, there is the definition of the project or the situation to be assessed and its guiding objectives, known as demand. In the step M, it relates to the work, tasks and organizational protocols and also includes the need of measuring. In the step A, all concepts are about the analysis itself. The step I is the moment of improving or incrementing. In the step C, control, prevention from prospective troublesome situation and implementation of management are the activities controlling the situation. R is Report. Some relevant technical and conceptual aspects for the comparison of these methodologies are illustrated in this paper. The steps of DMAICR were taken by a multifunctional team (multi-professional and multi-disciplinary) termed as focus group, composed by selected members of the company and supported by experts in ergonomics. PMID- 22316950 TI - Analysis of the lifted weight including height and frequency factors for workers in Colombia. AB - Factors related to the height of the load and the frequency of handling have become a way to predict the acceptable standard weight lifted for workers whose main task is the manual lifting of materials and measuring the conditions is important to determine a maximum weight lifted. This study was conducted to twenty (20) workers between eighteen (18) and forty (40) years old with a minimum six months experience and belonging to the warehouse and packaging area of a dairy products company. Consideration was given to three different heights such as knuckle, shoulder and total height as well as frequencies of 2, 4 and 6 times per minute. Average values for lifted weight were 17.9306 +/- 2.37 kg. The conclusions and recommendations included a review of legislation related to Colombian maximum acceptable weight of lifting due to the current law does not match the acceptable weight handled in this research. PMID- 22316951 TI - Analysis of the workload imposed on the workers of the imprint and cutting/welding sectors of a flexible packaging manufacturer. AB - This article presents a study on the evaluation of the workload imposed to workers of two sectors of a flexible packaging manufacturer that operates in three shifts. The workers are allocated in one of the shifts (morning, evening and night shifts) without evaluation of their chronotype and/or social needs. The Imprint sector has a more dynamic work, which is done only by man due to the effort demanded by handling loads. The work in the Cutting/Welding sector is static, done mainly by women. The results showed that the overall workload was the same in the Imprint and Cutting/Welding sectors, because physical effort for load handling is higher in the former but the latter involves high static load. The levels of urinary catecholamines and salivary cortisol were consistent with the workers biological clock showing that none of the workers changed his/her biological cycle to accommodate to the time of the shift schedule. PMID- 22316952 TI - The RFad Method--a new fatigue recovery time assessment for industrial activities. AB - This paper presents a study about fatigue recovery time assessment processes in work activities. It came about due to a demand presented by an automotive industry giant, in need of updating existing cycle time sheets and TAKT time parameters. The company decided to hire an Ergonomics Laboratory with ties to a major Brazilian University in order to evaluate current conditions and establish a new method to either calculate recovery times or validate existing assessment criteria, based in the ergonomics evaluation of the work activities. It is clear that there has been evident evolution in the industrial sector in the past two decades. It brought up fast modernization of industrial processes, not only in production but also in terms of management systems. Due to improved computer and robotics systems, combined with overall operational advancements - like the use of lighter hand tools and more effective hoist systems - most work activities have had its physical effort requirements reduced in the past decades. Thus, compensation factors built into production times need to be reviewed in order to avoid unnecessary costs associated to them. By using ergonomics considerations, we prevent simply removing the physical variables built in rest time calculations without taking on account, for example, additional cognitive load represented by the use of more sophisticated pieces of equipment. PMID- 22316953 TI - Noise analysis in professional office chairs. AB - The noise caused by the movement of users on their chairs in the work environment may indicate structural weaknesses and risk, and still significantly reduce productivity by increasing employees stress level. By understanding the activities to be developed in a work place one may understand what should be necessary to a good development, thereafter a search for improvement of labor activity with the aim of better use of resources in the operation of product use may be done. The analysis of the incremental variation of noise in professional chairs aims to identify its origin and the time the emission of noise starts during the period of use, its development and the major causative agents. Determining the characteristics of the sound of different materials and adjustments mechanisms of the chair can determine how different materials interact with each other. The measurement of these noises in an acoustic isolated room using directional microphones, if recorded and analyzed properly makes it possible to investigate and orientate to suspect elements in order to propose solutions and identify the quality of other similar chairs. Based on the results recommendations can be established for the orientation of users, managers and people responsible for the acquisition of the products, inducing them to review the employment of materials and the choice of the processes of production. These aspects are not covered in the Brazilian ergonomics norms and standards in the use of chairs. PMID- 22316954 TI - The risk of developing repetitive stress injury in seamstresses, in the clothing industry, under the perspective of ergonomic work analysis: a case study. AB - This study presents the sewing task with the approach of the ergonomic analysis of the work, in the seam activity in a clothing industry to identify the relationship between the use of different sewing machines and the activity of sewing pants and blouses, which brings larger risk for the development of work related musculoskeletal disorders. It was done a study of transverse and exploratory cut, in that was used a methodology control of multiple analysis of variables. The population objective was the workers that exercise the activity in the section of makings, with 93 workers, being 54,8% sewing auxiliary and 45,2% dressmakers. Most is single (75,3%), has the 2nd complete degree (58,0%) and the medium age was 25 years old. As results were observed that the machines serger, zig zag and traveti are classified as of high risk of developing work related to musculoskeletal disorders, that the postures assumed during the execution of the tasks were classified as bad or terrible, and that the workstations were just classified as reasonable. It was concluded then, that a relationship exists among the task of sewing pants and blouses, and the risk of the development of work related to musculoskeletal disorders. PMID- 22316955 TI - The regulation of work activity and the new labor and production contexts. AB - In recent decades, there has been a rise in the use o lean production model techniques. Through this approach, companies become more flexible, a fact that increases the interest in studies regarding the introduction of this model in businesses and its impacts on working conditions. Important observations concerning ergonomics, such as the theme of work activity regulation, have been highlighted in such studies. This article aims to discuss strategies and regulations adopted by the workers on assembly lines that are considered flexible. The article presents the results of a study in a company that adopts some lean production techniques. The study was analyzed using the activity analysis as one of the premises of the Ergonomic Work Analysis (EWA). Many aspects of the traditional assembly line remain present in the scenario that was studied, however a new language was employed and aspects in the nature of regulations demonstrate that the relation with lean production techniques influence the operators' operational modes. PMID- 22316956 TI - The footwear factory's assembly sector: opposing organizational structure and quality from the ergonomic work analysis. AB - Data from 2006 indicated that Brazilian footwear leather industry was composed of approximately 9,488 formally registered establishments, considering the leather industry, footwear and leather goods. It was responsible for 211,582 people employed. However, in spite of having many employees, this kind of organization found several problems when analyzed from the ergonomics view. With this premise, then, in order to identify bottlenecks and other engineering problems that could cause discomfort and motivation lack among workers, leading directly to the loss of the product quality, the assembly sector of women's shoes factory was characterized. PMID- 22316957 TI - Evaluation of the impact of shiftwork and chronotype on the workers of the imprint and cutting/welding sectors of a flexible packaging manufacturer. AB - This article presents a study on the impact of shiftwork and chronotype on the perception of the work conditions, workload and adjustment to shiftwork by the workers of two sectors of a flexible packaging manufacturer, which operates in three fixed shifts. The workers are allocated in one of the shifts (morning, evening and night shifts) without evaluation of their chronotype and/or social needs. The workers' evaluation of the shift system and their work show that they prefer a fixed shift and to work in a shift compatible with their chronotype. The workers with chonotype uncompatible with the shift time tend to be less satisfied with the work conditions and content and feel more discomfort/pain. PMID- 22316958 TI - Human motion behavior while interacting with an industrial robot. AB - Human workers and industrial robots both have specific strengths within industrial production. Advantageously they complement each other perfectly, which leads to the development of human-robot interaction (HRI) applications. Bringing humans and robots together in the same workspace may lead to potential collisions. The avoidance of such is a central safety requirement. It can be realized with sundry sensor systems, all of them decelerating the robot when the distance to the human decreases alarmingly and applying the emergency stop, when the distance becomes too small. As a consequence, the efficiency of the overall systems suffers, because the robot has high idle times. Optimized path planning algorithms have to be developed to avoid that. The following study investigates human motion behavior in the proximity of an industrial robot. Three different kinds of encounters between the two entities under three robot speed levels are prompted. A motion tracking system is used to capture the motions. Results show, that humans keep an average distance of about 0,5m to the robot, when the encounter occurs. Approximation of the workbenches is influenced by the robot in ten of 15 cases. Furthermore, an increase of participants' walking velocity with higher robot velocities is observed. PMID- 22316959 TI - Ergonomics in the formation of work condition quality. AB - The specific organizing the conditions of executing the job makes up the essential decisive about possibility obtainment element of competitive superiority. The ergonomic requirements are essential element of this process. They unite the environment of work with principles of the SCR, causing enlargement the man's part in development of enterprise. PMID- 22316960 TI - Integration of human factors principles in LARG organizations--a conceptual model. AB - Nowadays many companies are undergoing organizational transformations in order to meet the changing market demands. Thus, in order to become more competitive, supply chains (SC) are adopting new management paradigms to improve SC performance: lean, agile, resilient and green (LARG paradigms). The implementation of new production paradigms demands particular care with the issues related with Human Factors to avoid health and safety problems to workers and losses to companies. Thus, the successful introduction of these new production paradigms depends among others on a Human Factors oriented approach. This work presents a conceptual framework that allows integrating ergonomic and safety design principles during the different implementation phases of lean, agile, resilient and green practices. PMID- 22316961 TI - Production layout improvement in emergency services: a participatory approach. AB - Volunteer fire department is a service that responds emergency situations in places where there are no military emergency services. These services need to respond quickly, because time is often responsible for the operation success besides work environment and setup time interfere with the prompt response to these calls and care efficiency. The layout design is one factor that interferes with the quick setup. In this case, the spaces arrangement can result in excessive or unnecessary movements; also the equipment provision may hinder the selection and collection of these or even create movement barriers for the workers. This work created a new layout for the emergency assistance service, considering the human factors related to work through the task analysis and workers participation on the alternatives of improvement. The results showed an alternate layout with corridors and minimization of unusable sites, allowing greater flexibility and new possibilities of requirements. PMID- 22316962 TI - Ergonomic analysis of workplaces in the iron casting industrial pole in Claudio, Minas Gerais--Brazil. AB - Brazil is currently recognized as the 10th largest producer of castings, and the city of Claudio, MG is known worldwide as the "Greatest foundry and metallurgical pole in Latin America", with more than 80 companies. However, this large number of enterprises and increasing investments in product development has demanded an increase in manpower and working hours of workers in the sector, proportionally increasing the incidence of occupational related health problems like RSI (repetitive strain injury), WMSDs (work-related musculoskeletal disorders) and industrial accidents. This article aims to characterize the industry from previously conducted case studies to relate the main causes of occupational diseases and outline possible interventions through design, showing how this tool can contribute to improve the working environment, workplace, tools and equipment through ergonomics adjustments. PMID- 22316963 TI - The integrated assessment of occupational risks in a pharmaceutical manufacturing plant. AB - Pharmaceutical plants are usually characterized by workplaces with quality levels generally higher than in other manufactoring sectors since healthcare products need to be produced in special conditions, keeping under a strong control hygiene, chemical and biological contaminants, and giving a particular emphasis on equipment maintenance. Limited physical work load, a low rate of injuries and work related pathologies together with a high level of quality process control contribute to consider pharma work conditions as generally light and safe. In this kind of contexts risk assessment cannot be based on factors individually considered, neither work load can be essentially measured on material handling and physical effort. Risk assessment and work environment improvements, on the contrary, have to be studied by an integrated view point. The paper presents methodologies and results of the applied research project IntegrARE (INTEGRated Assessment of Risks within Ergonomics) aimed at analyzing, in a big solid forms pharmaceutical plant, three different risk categories - architectural, ergonomic and active pharmaceutical ingredients risks - in order to highlight possible interactions on workers health, safety and wellbeing. After a detailed risk situations survey, singularly analyzed by a number of ad-hoc procedures, the study presents a methodology for integrated assessment of risks, aimed at identifying and evaluating integrated effects increasing or triggering risk situations for workers. PMID- 22316964 TI - Ergonomic evaluation of processes and products in the manufacture of upholstery. AB - This study aimed to perform an ergonomic evaluation of industrial processes and products - upholstered sofas - produced in the furniture cluster of Uba-MG. The used material was collected from two sofas upholstered industries associated with the union of the furniture industries of Uba region, located in Minas Gerais estate, Brazil. As for the product were evaluated dimensionally 29 upholstered sofas, with 12 being produced by industry "A" and 17 being produced by industry "B". As for the process, were evaluated: the socioeconomic profile of the worker and environmental factors of lighting and noise. The main results of this study showed that the upholstered sofas produced by industries, in general, fulfilled to the recommendations set out in the work in relation to the backrest height and useful seat depth. All the sofas, however, proved to be inadequate in relation to the seat height to the floor and the dimensions of the armrests Regarding environmental aspects, it was observed that in both industries, the activities in most jobs are performed under adverse conditions to the health and safety of workers and nonconformity with the limits set by Brazilian regulatory standard used in this work. PMID- 22316965 TI - A socio-technical approach for improving a Brazilian shoe manufacturing system. AB - This article presents a macroergonomic intervention in a footwear company in Rio Grande do Sul, Brazil, to improve both the quality of life of the employees and productivity by optimizing the traditional Taylor/Ford work organization. Multi functionality and team working were implemented as means of making tasks more flexible and richer and the working hours were changed. The results showed a reduction in human and material resource costs and a consequent improvement in health and workers quality of life. Although middle managerial staff displayed strong resistance to the project and to breaking traditional production paradigms, the socio-technical system has been implemented throughout the plant and is expected to end up becoming the benchmark for other companies in the sector. KEYWORDS: Macro-ergonomics, footwear industry, organization work. PMID- 22316966 TI - Participative development of packages in the food industry--evaluation of ergonomics and productivity by objective measurements. AB - Rationalizations generally have a negative effect on health and known risk factors for musculoskeletal disorders. These effects may be reduced by paying attention to modifiers as worker participation and a resonant management style. In this study a participatory approach was used in the food industry in order to improve ergonomics and productivity. The food industry shows a high prevalence of musculoskeletal disorders, and repetitive manual work occurs extensively. Prototypes of new packaging solutions were developed in three cases, and compared in a simulated production to the existing production system through direct measurements of working postures and muscle activity, ratings of physical load, and general productivity data. Measured and rated ergonomic exposures showed that workload was significantly lower for the prototypes, in all three cases. In two cases, the number of handling operations included in the packaging operations were greatly reduced with the prototype package, as were production costs. The impact on disorders of the obtained load reductions is difficult to assess, but we believe that in "critical" situations like this, even small improvements may have an effect. This study shows that workloads during manual handling of packages as well as production costs can be reduced by applying participative development of packages. PMID- 22316967 TI - Ergonomics and Kaizen as strategies for competitiveness: a theoretical and practical in an automotive industry. AB - With increased international competitiveness in the automotive industry, came the concern of the companies save costs and lower production costs. For this purpose many ways are designed to reduce costs and waste of raw materials and reduce activities that do not aggregate value to manufacturing processes. In the early XVII appears the manufacturing system, which processes were hard with little concern for the health and safety of employees and conditions of the workplace. After the advent of the production system called lean manufacturing, a new paradigm in terms of production system capable of providing high levels of productivity and quality. It is based on waste elimination that occur during the production process. After began a new way of thinking, creating a culture of continuous improvement and lean process with no waste and reducing costs, without neglecting the welfare worker and improving the conditions of their work environment. This paper presents a reflection on the application of ergonomics in a lean production system of an automotive industry, using methodology based on the Kaizen (Continuous Improvement) to gain performance and improving the conditions of the workplace, also will be presented with positive and negative points in using this methodology in relation to ergonomics. The research will be conducted by collecting data 'in loco' and interviews with workers. Some studies show that in companies that are lean system and using the methodology of Kaizen, the results of product quality, levels of absenteeism and accidents are better than those obtained in companies that do not apply the same concept. PMID- 22316968 TI - Modified track shoes and their effect on the EMG activity of calf muscles. AB - Although track and field spike shoes are crafted for runners, these shoes are not designed for regular walking. With such shoes, runners may eventually encounter serious chronic injuries such as plantar fasciitis, shin splints, achilles tendinitis, chondromalacia, and iliotibial band syndrome. To address this problem, a modified spike shoe was tested and compared to a regular spike shoe. The modification consists of adding a removable heel to the shoe sole in order to reduce the flexion of the foot and properly level the foot for walking. Nine healthy participants performed walking drills at 2 and 3 mph, using the original and the modified shoes. Electromyography (EMG) measurements were used to evaluate muscle activities. Participants also rated their discomfort on a 0-10 scale. Results show that the use of modified shoes resulted in a reduction of 22% and 24.25% EMG activity for the tibialis and gastrocnemius muscles, respectively. Comfort ratings increased by an average of 2.7, 2.6, 3.9, and 4.2 points at the knees, calves, ankles, and feet, respectively. PMID- 22316969 TI - The specification of personalised insoles using additive manufacturing. AB - Research has been conducted to explore a process that delivers insoles for personalised footwear for the high street using additive manufacturing (AM) and to evaluate the use of such insoles in terms of discomfort. Therefore, the footwear personalisation process was first identified: (1) foot capture; (2) anthropometric measurements; (3) insole design; and (4) additive manufacturing. In order to explore and evaluate this process, recreational runners were recruited. They had both feet scanned and 15 anthropometric measurements taken. Personalised insoles were designed from the scans and manufactured using AM. Participants were fitted with footwear under two experimental conditions: personalised and control, which were compared in terms of discomfort. The mean ratings for discomfort variables were generally low for both conditions and no significant differences were detected between conditions. In general, the personalisation process showed promise in terms of the scan data, although the foot capture position may not be considered 'gold standard'. Polyamide, the material used for the insoles, demonstrated positive attributes: visual inspection revealed no signs of breaking. The footwear personalisation process described and explored in this study shows potential and can be considered a good starting point for designer and researchers. PMID- 22316970 TI - The reality of the women who make our lives easier: experience in a company that assemblies electric motors in Venezuela. AB - OBJECTIVE: intervene a workline throughout ergonomic approach to diminish incidence of Carpal Tunnel Syndrome (CTS). METHODS AND MATERIALS: an ergonomic intervention study was developed in workstations with highest index of musculoskeletal disorder (MED) associated to cumulative trauma. The Deparis method, Reba and Ocra check list methods were used, also morbility reviewes. National and international ethics criteria were carried out. RESULTS: workers identified 3 fundamental issues using the Deparis method: repetitive activities, postures adopted and uncomfortable furniture. The analysis of the workstation with Reba and Ocra methods before the changes, evidenciated that 56% of postures adopted were high risk postures, the 44% remaining were medium and low-risk. Following the active pause program (APP), furniture changes and work rhythm decrease, was noted that the risk of suffering MED decreased. The morbility review, drop in consults of musculoskeletal system (MES) related to CTS observed. The APP was well accepted by women, but not initially men. DISCUSSION: the research show that when the work rhythm decreases, the symptom of MES related to CTS have a remarkable decrease, also that changes in the furniture, generate great ergonomic differences and changes in the work environment are not possible if workers don't empower the tools to make-it. PMID- 22316971 TI - State of scientific knowledge about the need of recovery time at specific workplaces and recommendations for further research. AB - Research activities to determine the need of recovery time at work were mainly performed in the 1970s and 1980s. Previous studies were largely based on expert opinions or were generated within small and non-representative groups. Often, laboratory experiments were carried out with a low number of subjects. Especially during the last decade, only little additional scientific knowledge was generated on this topic. The very resource intensive development of more detailed results based on the existing level of scientific knowledge is assumed as one reason for this. In general, it seems to be reasonable to continue further research on the knowledge generated in previous studies, but implement larger samples and more representative groups. Besides, according to monotonous manual work, more research is especially needed regarding relative operating forces and operation frequencies taken grip conditions and hand/body position into account. PMID- 22316972 TI - Software development for the evaluation of the ergonomic compatibility on the selection of advanced manufacturing technology. AB - Advanced Manufacturing Technology (AMT) is one of the most relevant resources that companies have to achieve competitiveness and best performance. The selection of AMT is a complex problem which involves significant amount of information and uncertainty when multiple aspects must be taken into consideration. Actual models for the selection of AMT are found scarce of the Human Factors and Ergonomics perspective which can lead to a more complete and reliable decision. This paper presents the development of software that enhances the application of an Ergonomic Compatibility Evaluation Model that supports decision making processes taking into consideration ergonomic attributes of designs. Ergonomic Compatibility is a construct used in this model and it is mainly based in the concept of human-artifact compatibility on human compatible systems. Also, an Axiomatic Design approach by the use of the Information Axiom was evolved under a fuzzy environment to obtain the Ergonomic Incompatibility Content. The extension of this axiom for the evaluation of ergonomic compatibility requirements was the theoretical framework of this research. An incremental methodology of four stages was used to design and develop the software that enables to compare AMT alternatives by the evaluation of Ergonomic Compatibility Attributes. PMID- 22316973 TI - Construction of a survey to assess workload and fatigue among AMT operators in Mexico. AB - Operators of machinery classified as Advanced Manufacturing Technology (AMT) are exposed to high levels of workload and fatigue. However, only few studies have been conducted on this topic in Hispanic-American countries workers. Several instruments be used to assess workload and fatigue; however, only few of them have been adapted to Spanish language. This paper reports on the development and validity testing of a survey instrument in Spanish, aiming to subjectively assess workload and fatigue among AMT operators in Mexico. METHOD: After an exhaustive literature review in search of already available measurement instruments, they were adapted for content and later translated into Spanish; a pilot test was conducted to evaluate validity and reliability; afterwards appropriate modifications were made to the testing instruments. Final version of the instrument was applied to a group of 121 operators of CNC lathes. Reliability was analyzed using KMO and Cronbach alpha indices. RESULTS: For the assessment of workload, both NASA-TLX and ISTAS 21 methods were incorporated to the survey instrument. As for fatigue assessment tools, these were SOFI-S, FAS and OFER questionnaires. RESULTS show KMO value and Cronbach alpha above 0.6.Conclusions. The survey instrument as designed, allows the collection of reliable and valid data regarding workload and fatigue among AMT operators in Mexico. PMID- 22316974 TI - Fuzzy modelling and efficiency in health care systems. AB - American Medical Institute reports that each year, because of the medical error, minimum fifty thousand people are dead. For a safety and quality medical system, it is important that information systems are used in health care systems. Health information applications help us to reduce the human error and to support patient care systems. Recently, it is reported that medical information systems applications have also some negative effect on all medical integral elements. The cost of health care information systems is about 4.6% of the total cost. In this paper, it is tried a risk determination model according to principles of fuzzy logic. The improvement of health care systems has become a very popular topic in Turkey recent years. Using necessary information system; it became possible to care patients in a safer way. However, using the necessary HIS tools to manage of administrative and clinical processes at hospitals became more important than before. For example; clinical work flows and communication among pharmacists, nurses and physicians are still not enough investigated. We use fuzzy modeling as a research strategy and developed sum fuzzy membership functions to minimize human error. In application in Turkey the results are significantly related with each other. Besides, the sign differences in health care information systems strongly effects of risk magnitude. The obtained results are discussed and some comments are added. PMID- 22316975 TI - Using human factors engineering to improve patient safety in the cardiovascular operating room. AB - Despite significant medical advances, cardiac surgery remains a high risk procedure. Sub-optimal work system design characteristics can contribute to the risks associated with cardiac surgery. However, hazards due to work system characteristics have not been identified in the cardiovascular operating room (CVOR) in sufficient detail to guide improvement efforts. The purpose of this study was to identify and categorize hazards (anything that has the potential to cause a preventable adverse patient safety event) in the CVOR. An interdisciplinary research team used prospective hazard identification methods including direct observations, contextual inquiry, and photographing to collect data in 5 hospitals for a total 22 cardiac surgeries. We performed thematic analysis of the qualitative data guided by a work system model. 60 categories of hazards such as practice variations, high workload, non-compliance with evidence based guidelines, not including clinicians' in medical device purchasing decisions were found. Results indicated that hazards are common in cardiac surgery and should be eliminated or mitigated to improve patient safety. To improve patient safety in the CVOR, efforts should focus on creating a culture of safety, increasing compliance with evidence based infection control practices, improving communication and teamwork, and designing better tools and technologies through partnership among all stakeholders. PMID- 22316976 TI - Workaround identification as an instrument for work analysis and design: a case study on ePrescription. AB - This paper investigates workarounds occurring while pharmacists use an electronic prescription (ePrescription) application. ePrescription enables physicians to send prescriptions electronically to pharmacies and was recently introduced in Greece as a solution for controlling the ever-increasing medication costs and improving patient safety. The research was carried out in two phases: (i) review of the relevant documentation, (ii) fieldwork (field observations and semi structured interviews with the pharmacists) in three pharmacies. The workarounds identified fall into five categories and namely: (a) bypass of ePrescription application (i.e. ePrescription application is not used at all), (b) temporal nonconformity in the use of ePrescription application (i.e. usage of the application, but not at the formally specified time), (c) catachresis of ePrescription application (i.e. usage of the application, but not according to the intended way), (d) ePrescription application substitution by another electronic application, and (e) delegation of ePrescription application usage to non-authorized users. The outcome of the research can be used for the improvement of multiple work system elements such as the tools, the procedures, the organisational arrangements and the policies. PMID- 22316977 TI - Characterizing complexity in socio-technical systems: a case study of a SAMU Medical Regulation Center. AB - Complexity theory has been adopted by a number of studies as a benchmark to investigate the performance of socio-technical systems, especially those that are characterized by relevant cognitive work. However, there is little guidance on how to assess, systematically, the extent to which a system is complex. The main objective of this study is to carry out a systematic analysis of a SAMU (Mobile Emergency Medical Service) Medical Regulation Center in Brazil, based on the core characteristics of complex systems presented by previous studies. The assessment was based on direct observations and nine interviews: three of them with regulator of emergencies medical doctor, three with radio operators and three with telephone attendants. The results indicated that, to a great extent, the core characteristics of complexity are magnified) due to basic shortcomings in the design of the work system. Thus, some recommendations are put forward with a view to reducing unnecessary complexity that hinders the performance of the socio technical system. PMID- 22316978 TI - Examination of computer task exposures in radiologists: a work systems approach. AB - Radiologists are intensive computer users as they review and interpret radiological examinations using the Picture Archiving and Communication Systems (PACS). Since their computer tasks require the prolonged use of pointing devices, a high prevalence of Musculoskeletal Disorders (MSDs) is reported. The first phase of this study involved conducting a Cognitive Work Analysis in conjunction with a Participatory Ergonomics approach to perform a total work system analysis. We also conducted an ergonomic survey as well as collected computer use data, specifically for the mouse and keyboard. The goal of the study was to reduce the physical exposures for radiologists. This paper presents Phase I results describing the analyses and redesign process of the radiologists tasks, training design, computer use, and selected survey results. PMID- 22316979 TI - Ergonomic assessment among radiology technologists: a survey in a hospital. AB - This article is the result of an Ergonomic Diagnosis in a study for a Specialization Course in Ergonomics. The research is being done in a public hospital in the city of Rio de Janeiro, where the target system is the radiology sector. For diagnosis purposes, subjective techniques were used, such as an open ended survey, Corlett questionnaire and techniques for evaluating ergonomic risk such as Owas and Rula. Systematic observation was emphasized using photos and films. Preliminary observations made to the radiographers found that these professionals suffer risks of physical and verbal harassment, as well as sexual harassment. Most of them feel discriminated against in terms of race and accumulate activities demanding a lot of attention, as the medical diagnosis and subsequent procedures will depend on the outcome of this task. They accumulate tension due to the weight of responsibility, since there are cases where the patient has risk of death. PMID- 22316980 TI - Care giving and nursing, work conditions and Humanitude(r). AB - Increased lifespan in western societies causes the increase of hospitalization in the old age, notably for patient showing forms of dementia including Altzheimer disease. These patients relate poorly to care givers and nurses, and cases of maltreatment have repeatedly been reported. To prevent abuse and increase patient's quality of life, Gineste and Pelissier (2007) proposed a philosophy of care based on the Humanitude(r) concept. Acknowledging that being human is being vertical and related to other humans, the pillars of Humanitude(r) are gaze, touch, talk, and standing. These modes of relation are systematically developed in care giving techniques derived from the concept. After several studies in geriatric hospitals, to assess psychosocial and ergonomic aspects of work, we present an analysis of the gap between the logic of human care and the logic of hospital organization, impacting employees work conditions and psychological welfare. Care giving is not only a "one to one" relation with the patient but needs to be integrated in the whole organization. Psychologists and ergonomists should be instrumental in defining the project and the organization linking human care giving towards the patients and better work conditions for healthcare employees. PMID- 22316981 TI - Ergonomics in the psychiatric ward towards workers or patients? AB - INTRODUCTION: Patient's aggressive behavior is one of the major problem in the psychiatric ward. Here we present the preliminary results of a psychiatric ward case-study, of a public hospital in the Chieti province, in order to plan ergonomic improvement. METHOD: We applied the Method of Organizational Congruencies in the psychiatric ward in order to study the relationship between organized hospital work and nurses wellbeing in a 24 hour shifts. RESULTS: We observed 58 main phases in the three work shifts. The technical actions are mainly those of any hospital wards (shift briefing, preparing and administering drugs, recording data on clinical charts, etc.). We found important differences mainly due to the nurses overcontrol activities on the patients behavior (preventing suicides or self destructive behavior), the occurrence of restraint procedure towards patients, the pollution due to patient's cigarette smoke. DISCUSSION: The fear of patient's self destructive behavior or other aggressive behaviour are the main cognitive and social aspects of this hospital ward. Nurses working in this psychiatric ward have to accept: locked doors, poor and polluted environment, restraint procedure with high risk of aggression and no availability of mental health care programs. A new interdisciplinary concept for ergonomics in psychiatry setting may represent a challenge for both nurses and patients and the community. PMID- 22316982 TI - Impact of ergonomics risk among workers in clothes central distribution service in a hospital. AB - BACKGROUND: In health care services, the workers from laundry and linen services are exposed to various occupational hazards, including the ergonomic risk. Were decided to study the effect of ergonomic factors at work in the musculoskeletal system for employees in this sector. METHODS: Cross-sectional study conducted in a mid-sized general hospital in Brazil. Site visit was conducted to apply recognition of occupational hazards and work activities flow. Medical evaluation of twenty-one workers was performed for designing the health status of them, focusing on orthopedic disorders. RESULTS: Their activities are to distribute clothes in all units of hospital care in order to organize and maintain supplies. The principal complaints were back pain (43%) and shoulder pain (24%). The ergonomic risk happens due to repeated movements of lumbar flexion in sealing, raising the arms above shoulder level in storage and transportation of loads on the distribution of clean clothes. CONCLUSIONS: The complaints by workers are consistent with the overloads identified in the evaluation of jobs. It is recommended to adjust anthropometrically the sealing workplace; the availability of stairs; the implantation of trolleys with four swivel wheels; short breaks during the workday; and to stretch the muscles before and during work. PMID- 22316983 TI - An ergonomic analysis of work in the process of professional rehabilitation in Brazil. AB - The purpose of this study is to describe the use of the Ergonomic Analysis of Work (EAW) in the process of rehabilitating workers, insured by the National Institute of Social Security (INSS) in Brazil, and to conduct a brief analysis of the instrument used by this body. Information obtained from EAW enabled the demand, the requirements of the activity and the skills needed to perform the tasks in the workplace to be determined, thus aiding the decision of the INSS as to rehabilitating the workers and their return to their jobs. PMID- 22316984 TI - Ergonomic constraints among nursing workers in the sectors of emergency care in two public hospitals in Brazil. AB - The goal of this study was to comprehensively identify ergonomic constraints among nursing workers in two public hospitals in Brazil. We used a qualitative research design and conducted interviews, field observation and performed a subjective questionnaire with nurses of emergency care sectors. The Cronbach alpha technique was used to determine the internal consistency of the questionnaire. Based on this qualitative study, we identified some ergonomic constraints related to work environment, biomechanics/anthropometrics, work organization and work station (hospital direction). PMID- 22316985 TI - Injury prevention in physiotherapists--a scientific review. AB - This review targeted all research previously conducted on the topic of musculoskeletal disorders and injury among physiotherapists, with a particular focus on studies that had examined individual, physical and psychosocial risk factors and provided suggestions or recommendations to prevent such injuries. Scientific literature published in English languages was searched using electronic way. A total of 17 appropriate studies were located and examined, most of which had focused on the prevalence of musculoskeletal disorders/pan or any other injury. From the review, it was shown that major risk factors among the physiotherapist were manual therapy, repetitive movement, awkward and static posture, physical load, lifting and transferring, treating large number of patients treating in a single day, working while injured, years of experience. The preventive measures that described in these literatures were awareness of reporting of injury, use of less manual therapy, proper exercise, formulation of new devices, intervention at the level of workplace, work schedule allocation, proper training, ongoing risk assessment and control. PMID- 22316986 TI - Musculoskeletal disorder related to the work of doctors who perform medical invasive evaluation. AB - BACKGROUND: Experts in medical invasive evaluations, like colonoscopy, could be exposed to ergonomic risks during their work. Little attention has been given to these spectrum of occupational health. Its aimed to analyze possible clinical problems related to upper limb of physicians who perform those exams. METHODS: Cross-sectional study in a health service in Sao Paulo, Brazil. For evaluation of the workplace of the colonoscopist physician were applied two tools: Couto's check list and Sue Rodgers Method. The results direct the potential risk to upper limb injuries. RESULTS: The procedure is done and the final report is issued. There are no mandatory pauses during workday. The dominant hand holds the tube insertion with pincer movement during the exam, digital prehension being necessary at times. For this activity the employee has to use some strength. Couto's check list indicates a significant biomechanical factor. Sue Rodgers's Method states high ergonomic risk for dominant hand/wrist/fingers. CONCLUSION: The main risk for the development of health disorders are associated with the use of force and repetitive movements of hands. The adoption of regular breaks to recover most of the structures required is recommended. PMID- 22316987 TI - Work-related musculoskeletal discomfort and injuries in Australian optometrists. AB - Work-related musculoskeletal discomfort and injuries are reported by optometrists. The purpose of this paper is to describe the process used to investigate work-related discomfort in Australian optometrists. A multistage project was conducted which included questionnaires, interviews and onsite observations. Participants, with and without self-reported discomfort, included clinical optometrists, optometry students and clinical teachers. The various stages of the study developed over the course of the project, primarily in response to results collected at various stages. A multistage approach proved valuable for confirming results and testing hypotheses, and for investigating different groups of workers (clinicians, teachers and students). General guidelines to reduce the risk of work-related discomfort in optometrists can be developed from this project. Specific recommendations and teaching curricula have been identified in this project as areas of future research and development. PMID- 22316988 TI - Risk reduction in musculoskeletal practice assistance professional nursing pilot in semi intensive care unit. AB - The hospitals mostly have a high level of complexity, diversity of services and, consequently, occupational risks. The tasks of mobilization and manual repositioning of patients may require professional of the physical demands due to the weight or excessive patient dependency, attitudes arising from inadequate to lean on a bed or work in a restricted area, sudden weight change that can occur if a patient loses balance or strength to change the position or while moving. These, among many other factors can cause or aggravate musculoskeletal problems in health care workers. These diseases translate into frequent musculoskeletal complaints, high rates of absenteeism, licenses and problems of prolonged labor, creating a vicious cycle that compromises patient safety and performance of institutions. The literature has suggested the administration of courses on handling and transportation of patients as one of the most important strategies to reduce the incidence of problems in the spine between the worker's healths. An exercise program emphasizing global distension and strength, mainly the posterior chain muscles (dorsal region), held twice a week, combined with an approach to ergonomics can reduce musculoskeletal symptoms and absenteeism in nursing. PMID- 22316989 TI - Factors contributing to work related low back pain among personal care workers in old age. AB - This study aims to preliminary explore the work related and individual factors that contributed to the occurrence of low back pain (LBP) that affected work activities of Personal Care Workers (PCWs). A cross-sectional study was conducted to 36 PCWs in an old age home of Hong Kong. The study is divided into three parts: 1) a questionnaire to document the workload exposure factors and the musculoskeletal symptoms survey of the PCWs, 2) work posture evaluation; and 3) an evaluation of the physical fitness and lifting capacity of the PCWs. Univariate analyses were used to explore the risk factors associated with LBP that affected work activities. The results indicated that individual physical profile and lifting capacities did not contribute to occurrence of low back pain at work. For the work demand factors, the perceived physical demands in lifting and lowering heavy objects, awkward sustain neck and back postures, loading on the back, and perceived effort of cleaning task contributed to the occurrence of LBP. For the physical environment factors, thermal stress and improper ventilation were associated with the occurrence of LBP cases. For the individual factor, LBP cases were associated with workers' self perceived muscular effort, and perceived risk of mental illness in response to work requirements. PMID- 22316990 TI - Ergonomic evaluation of laparoendoscopic single-site surgery ports in a validated laparoscopic training model. AB - Although laparoendoscopic single-site surgery (LESS) is feasible among expert laparoscopic surgeons, it poses many technical challenges not seen in conventional laparoscopy (CL). Recent technological advancements in single incision instrumentation have created more interest and widespread usage of LESS. However, neither LESS nor its novel instrumentation have been thoroughly studied or evaluated using human factors and ergonomics techniques. Consequently, the aim of this study was to compare the physical performance of LESS to CL using a standardized task. Wrist and elbow angular movements, range of motion and physical discomfort were assessed for 24 novice participants. There were no significant differences for physical comfort/discomfort ratings or elbow and wrist flexion/extension range of motion between CL and LESS. However, wrist radial/ulnar range of motion was significantly greater in LESS compared to CL (p < 0.05). Additionally, wrist radial/ ulnar range of motion was significantly greater using the SILS Port compared to the GelPOINT (p < 0.05). Although further investigation is needed, LESS resulted in greater wrist deviation and range of motion due to the close proximity of the instruments, restrictive nature of the single-port devices, and the need to achieve adequate instrument triangulation and visualization. PMID- 22316991 TI - Musculoskeletal disorders in caregivers of children with cerebral palsy following a multilevel surgery. AB - The patients of cerebral palsy need assistance for their self activities which expose the caregivers to different risk factors of musculoskeletal disorders. But there is a scarcity of studies revealing the prevalence and the risk factors present among the caregivers of the cerebral palsy children. This lead to formulate a study to identify prevalence and risk factors among the caregivers of cerebral palsy children. Result revealed that most of the caregivers among both the groups were female (63.4% and 69.3%). The common age group of the children who underwent multilevel surgery was at the age group of 6 - 10 years. It has been observed that among the study group 56.5% were totally cooperative children. The Caregiver Strain Index value showed there is no significant difference among both the groups. Regional body pain of shoulder, elbow, upper back, lower back and ankle revealed a higher prevalence among the study group. Clinical diagnosis revealed prevalence of MPS, FMS and TOS among the study group were 27.6%, 24.5% and 23.0% respectively. Study further revealed that cooperativeness of the child was significantly associated with lower back pain, MPS, FMS and TOS among the study group. PMID- 22316992 TI - Preventive and curative importance of the baropodometric analysis for ergonomics and occupational health. AB - The pressure distribution on the plantar surface may reveal information not only about the feet structure, also it may bring out information about the entire body posture not only on health but also pathologic conditions. The application in ergonomics and occupational health gives access to the postural correction that on a long term may provoke professional injuries giving presition and security. This study is on 132 workers of Universidad de las Americas. PMID- 22316993 TI - Ergonomic and individual risk evaluation. AB - The ergonomic risks constitute a vital aspect of study and prevention for the worker's health, especially for people with different capacities. Very job has and implies certain type of risk for the worker's health, depending on the conditions it is done with the use of tools or without them. Aplicated techniques: posturogram, baropodometry, Schober test, biocinematic chain test, Fukuda test, propioceptiva plataform in personnel with special capabilities. PMID- 22316994 TI - Recognizing nurse stakeholder dissonance as a critical determinant of patient safety in new healthcare information technologies. AB - Proper identification of all stakeholders and the comprehensive assessment of their evolving and often conflicting Needs, Wants, and Desires (NWDs) is a fundamental principle of human factors science and human-centered systems engineering; it is not yet a consistent element in development and deployment of new health information technologies (HIT). As the single largest group of healthcare professionals, nurses are critical stakeholders for these new technologies. Careful analysis can reveal nurse stakeholder dissonance (NSD) when integrating new technologies into the healthcare environment. Stakeholder dissonance is a term that describes the conflict between the NWDs of different stakeholders which, if left unresolved, can result in dissatisfaction, workarounds, errors, and threats to patient safety. Three case studies drawn from the authors' experience in a variety of acute-care settings where new HITs have been recently deployed are examined to illustrate the concept of NSD. Conflicting NWDs, other stakeholders, and possible root causes of the NSD are analyzed and mapped to threats to patient safety. Lessons learned, practical guidance for anticipating, identifying, and mitigating NSD, future research and implications for HFE and nursing practice are discussed. PMID- 22316995 TI - How are nurses at risk? AB - The effectiveness of occupational health and safety management systems (OHSMS) can be understood through analysis of surveys such as the experiences of exposure to occupational hazards by Australian nursing occupations. How effectively OHSMS are implemented in the Australian health industry is unclear as few studies describe current hazard exposure patterns or the impact of OHSMS in the Australian health industry. This paper concludes from the analysis of an Exposure Survey of Australian nursing occupations that nursing occupations perceive themselves to be "at risk" of injury and/or management of OHS risk in work duties is affected by the patterns of hazard exposure, occupation group as well as employee attributes, perceptions, patterns and situations of work. The results highlight the top-rated hazards and imply that the perceptions of hazards in the workplace are different to actual risk experience (e.g. injury patterns). There is an unacceptable level of exposure to diverse hazards in Australian nursing occupations workplaces in regard to regulatory and performance obligations. Stronger strategies to achieve more effective risk treatment, integrate with hospital accreditation and quality programs are discussed to benefit system performance and the welfare of those in nursing occupations. PMID- 22316996 TI - Screening of risk from patient manual handling with MAPO method. AB - International standards highlight the steps required by risk assessment and involving first hazard identification, then risk evaluation and finally, if necessary, risk assessment. To check approach appropriateness to "risk evaluation" from manual patient handling through MAPO, a cross study was carried out in view of checking relationship between this new risk assessment model and occurrence of acute low back pain. After proper training the MAPO screening method was assessed in 31 wards, 411 exposed subjects of geriatric hospitals. At the same time health data were collected on occurrence of low back pain episodes during the last year both in the exposed subjects' group and the external reference group (n?237). Risk and clinical assessment data were tutored and checked by EPM research unit. The logistic analysis was used as a method to evaluate the relationship between risk index and acute low back pain. Investigating relationship between acute low back pain episodes and levels of MAPO screening index, carried out only with the people exposed who claimed to work for at least 30 hours per week (n = 178), showed definitely positive trends. The study results indicate that MAPO screening may represent a useful tool to estimate the risk from manual handling patients. PMID- 22316997 TI - Definition of design criteria of mechanical transfer: an interaction between engineering and health areas. AB - This study aims to analyze the factors that justify the low use of a mechanical transfer in the context of a long-term institution. It is a device intended for internal transportation of individuals who have mobility problems. The analysis involves researchers from the fields of health and engineering in order to generate design criteria that consider the needs of caregivers and patients of this institution. To understand the reality of this site and their specificities, was used Ergonomic Work Analysis. PMID- 22316998 TI - Biomechanical and organizational risk and prevalence of low back pain in the old adults caregivers of a nursing home in Joao Pessoa/PB. AB - The objective present study was to investigate the presence of low back pain in caregivers of a nursing home, related with the labored activities executed by these workers. 16 subjects were investigated, 15 female and one male, with 40,8 age average all being caregivers as their profession. It consisted of three phases, where the first concerns the analysis of the collective work, assessed in a perspective of caregivers, Second, a postural assessment to verify the retractions in such workers and the third stage was used Diagram of Corllet to identify the presence of signs and symptoms in caregivers. The study demonstrated that organizational and biomechanical factors are responsible for the high level of physical fatigue and presence of pain in 93,75% of the caregivers in some region of the body. 50% referred pain in the lumbar region. The results of the postural evaluation confirmed that the caregivers had alterations in the postural alignment, presenting retractions of the anterior and posterior chain. The suggestions are to minimize the risk factors of this productive process and the symptoms and signals presented from these workers by adoption ergonomic measures and the realization of a physical program with stretching and muscular strengthening of the muscles of the anterior and posterior body chain based on the method of Reorganization Postural Sensoperceptive. PMID- 22316999 TI - Study of musculoskeletal risks of the office-based surgeries. AB - Due to the cost and time benefits associated with patients and physicians, outpatient surgeries continue to become more and more popular over time. With the increase in the number of office-based surgical procedures, the prevalence of work-related musculoskeletal disorders (WMSDs) associated with office-based surgeries has been reported. The purpose of this pilot study is to ergonomically evaluate the risk of work-related musculoskeletal disorders of physicians/surgeons performing office-based surgery (OBS). Ergonomic assessment tools included Questionnaire, the BodyMap and the Rapid Upper Limb Assessment for measuring potential ergonomic concerns. The findings have shown that the ergonomic issues of greatest concerns were the discomforts in the neck, shoulders, arms/wrists, and back. Some additional comments were provided by the participants regarding the duration of discomfort or clarification on the frequency of their body discomfort. This study suggests that there is a considerable risk of musculoskeletal injuries of physicians/surgeons performing the OBS tasks. By properly using the ergonomic assessment techniques, valuable information on ergonomic OBS workplace design and selection could assist in the early interventions of WMSD prevention. PMID- 22317000 TI - Quantitative posture analysis of 2D, 3D, and optical microscope visualization methods for microsurgery tasks. AB - The purpose of this paper is to present a quantitative posture analysis of microsurgery tasks performed with different visualization methods. Microsurgery is traditionally performed using a binocular microscope; however surgeons are constrained by the optical eyepieces and are forced to assume joint angles that deviate away from neutral postures. This may be especially problematic for the neck and can increase surgeon discomfort and fatigue. Alternative visualization methods may improve surgeon posture by eliminating the constraints imposed by the microscope. This study examines both 2D and 3D heads-up displays as possible alternatives. Six subjects performed microsurgical tasks with each visualization methods for four hours. Quantitative posture analysis was done using Maxtraq software that tracks reflective markers on the subjects. The initial analysis of neck, upper arm, and elbow angles found significant differences between each display. A biomechanical analysis found that the differences in angles can result in loads on the neck joint that are twice as high in the microscope than the headsup displays. Although the alternative displays can result in better postures, improvements the display technology is needed to improve microsurgical task performance. PMID- 22317001 TI - Reducing latent errors, drift errors, and stakeholder dissonance. AB - Healthcare information technology (HIT) is being offered as a transformer of modern healthcare delivery systems. Some believe that it has the potential to improve patient safety, increase the effectiveness of healthcare delivery, and generate significant cost savings. In other industrial sectors, information technology has dramatically influenced quality and profitability - sometimes for the better and sometimes not. Quality improvement efforts in healthcare delivery have not yet produced the dramatic results obtained in other industrial sectors. This may be that previously successful quality improvement experts do not possess the requisite domain knowledge (clinical experience and expertise). It also appears related to a continuing misconception regarding the origins and meaning of work errors in healthcare delivery. The focus here is on system use errors rather than individual user errors. System use errors originate in both the development and the deployment of technology. Not recognizing stakeholders and their conflicting needs, wants, and desires (NWDs) may lead to stakeholder dissonance. Mistakes translating stakeholder NWDs into development or deployment requirements may lead to latent errors. Mistakes translating requirements into specifications may lead to drift errors. At the sharp end, workers encounter system use errors or, recognizing the risk, expend extensive and unanticipated resources to avoid them. PMID- 22317002 TI - Quality in radiotherapy: effective treatment and patient safety. AB - The purpose of this article is to understand the way in which medical physicists take into account treatment effectiveness and safety when selecting a treatment plan, with respect to the medical prescription and the technical, human and organizational resources available. Data-gathering was based on the allo confrontation method: 14 medical physicists from five different treatment centers commented on real treatment plans that had been drawn up by their colleagues. Results show that medical physicists have two means at their disposal to control treatment effectiveness and safety: risk avoidance and risk reduction. Risk avoidance is achieved when conceiving the solution. Risk reduction occurs after the design of the plan and consists in accompanying and assisting the radiographers at the work station where the treatment is carried out. PMID- 22317003 TI - A comparative study of occupancy and patient care quality in four different types of intensive care units in a children's hospital. AB - This paper reports a comparative study of occupancy and patient care quality in four types of intensive care units in a children's hospital,: an Infant Care Center (ICC), a Medical/Surgical (Med/Surg) unit, a Neonatal Intensive Care Unit (NICU), and a Pediatric Intensive Care Unit (PICU), each featuring a mix of multi bed and private room (PR) patient care environments. The project is prompted by interest by the project sponsor in a pre-occupancy analysis, before the units are upgraded to exclusive PR designs. Methods comprised, for each unit: (1) observations of ergonomic design features; (2) task activity analyses of job performance of selected staff; and (3) use of a survey to collect perceptions by unit nursing and house staff (HS) of indicators of occupancy and patient care quality. CONCLUSIONS: (1) the five most common task activities are interaction with patients, charting, and interaction with equipment, co-workers and family members; (2) job satisfaction, patient care, work environment, job, patient care team interaction, and general occupancy quality rankings by ICC and/or NICU respondents are significantly higher than those by other staff respondents; and (3) ergonomic design shortcomings noted are excess noise, problems with equipment, and work environment, job-related health, and patient care quality issues. PMID- 22317004 TI - Interventions to prevent needle stick injuries among health care workers. AB - Needle stick injuries (NSIs) are frequently reported as occupational injuries among health care workers. The health effects of a NSI can be significant when blood-to-blood contact occurs from patient to health care worker. The objective of this study was to evaluate whether the number of NSIs decreased among health care workers at risk in one Dutch academic hospital after introduction of injection needles with safety devices in combination with an interactive workshop. In a cluster three-armed randomized controlled trial, 23 hospital divisions (n=796 health care workers) were randomly assigned to a group that was subjected to the use of a 'safety device plus workshop', to a group that was subjected to a 'workshop only' or to a control group with no intervention. The combined intervention of the introduction of needle safety devices and an interactive workshop led to the highest reduction in the number of self-reported NSIs compared to a workshop alone or no intervention. For practice, the use of relatively simple protective needle safety devices and interactive communication are effective measures for reducing NSI's. PMID- 22317005 TI - Managing unforeseen events in anesthesia: collective trade-off between "understanding" and "doing". AB - This study aims to describe how anesthesia teams handle unforeseen events that may affect the patients' health. More precisely, it investigates the mechanisms of decisions made by anesthesia teams to manage unthought-of situations, i.e. situations that have not been foreseen as "possible" ones before their occurrence. An empirical study, based on the analysis of simulated situations, was conducted in a pediatric anesthesia service of a university hospital in France. The results highlighted three ways of managing unthought-of situations (determined management, cautious management and overwhelmed management). They support the hypothesis of a collective cognitive trade-off, whereby teams would behave as virtual operators, with their own collective trade-off between "understanding" and "doing". The discussion of the results questions the assessment criteria, the safety perspectives we adopt and the possible ways to improve the management of unforeseen situations. PMID- 22317006 TI - Improving wheelchair prescription: an analysis of user needs and existing tools. AB - Wheelchair users experience many situations that affect the stability and associated performance of their wheelchair. Stability is affected by user characteristics and abilities, environmental features and conditions, and wheelchair modification and accessories. Wheelchair prescribers need effective tools and methods to provide quantitative evaluation and prediction of the behavior of the user-wheelchair system in a variety of static and dynamic situations. Such information is very important to guide efficient management of associated risks and adjust chairs accordingly. This project involves a user centered approach for design and evaluation of a load cell based wheelchair stability assessment system (Wheel-SAS). Here, the current methods for assessing stability are described, and their shortcomings explained. The user-centered design approach being applied to the development of the associated Wheel-SAS hardware and software is described. Future work including semi-structured interviews and an online survey with wheelchair prescribers and associated healthcare professionals for deriving user requirements and a design specification for a load cell system for measuring dynamic wheelchair stability are detailed. PMID- 22317007 TI - Automatic sleep stage classification based on easy to register signals as a validation tool for ergonomic steering in smart bedding systems. AB - Ergonomic sleep studies benefit from long-term monitoring in the home environment to cope with daily variations and habituation effects. Polysomnography allows to asses sleep accurately, but is costly, time-consuming and possibly disturbing for the sleeper. Actigraphy is cheap and user friendly, but for many studies lacks accuracy and detailed information. This proof-of-concept study investigates Least Squares Support Vector Machines as a tool for automatic sleep stage classification (Wake-N1-Rem to N2-N3 separation), using automatic trainingset specific filtered features as derived from three easy to register signals, namely heart rate, breathing rate and movement. The algorithms are trained and validated using 20 nights out of a 600 night database from over 100 different healthy persons. Different training and test set strategies were analyzed leading to different results. The more person-specific the training nights to the test nights, the better the classification accuracy as validated against the hypnograms scored by experts from the full polysomnograms. In the limit of complete person-specific training, the accuracy of the algorithm on the test set reached 94%. This means that this algorithm could serve its use in long-term monitoring sleep studies in the home environment, especially when prior person specific polysomnographic training is performed. PMID- 22317008 TI - The impacts of painful noise in the apprehension of sound references on context of a big band. AB - This study aims to describe the painfulness applied to situations of teaching learning of a Big Band in a School of Music of a Brazilian Federal University. Moreover, the concept of what painful noise is will be developed, applied to this context. After Ergonomic Work Analysis [2], the following variables were selected to characterize the painful noise: volume, height, frequency, sound confluence and reverberation. To relate the influence of painful noise on modes operatives, were explained the operative strategies used by teacher and students during the performance in group of this Big Band. PMID- 22317009 TI - Horizontal plane sound source localization and auditory enhancement. AB - Accurate sound source localization has advantages for the performance of work by humans. The ability to accurately localize sound sources contributes to perception, decision making and task performance. Two studies were conducted to investigate the prevalence of accurate sound source localization and the enhancement that spatially separated sound source locations can have on speech perception. The first study was conducted to characterize the ability to detect the location of horizontal plane sound sources. A sample of 117 participants with the hearing capacity within the normal limits participated in the study. The results indicated that sound sources located towards the front of the participant were identified more frequently than those sound sources located towards the rear positions. Based on the results found in the first study, a second study was conducted to assess performance within a listening task. Three different spatial configurations were used to assess if similar trends in performance translated to sound sources through headphones. Fifteen research participants performed a Coordinated Response Measure (CRM) task requiring the identification of a speech phrase and its associated information for a diotic configuration and two different spatial sound source configurations. Performance measured for the diotic configuration was significantly (p(0.05) less than for the two spatial configurations. The current studies indicate distinct advantages of utilizing localized sound sources to present auditory signal and speech to listeners. PMID- 22317010 TI - Moral harassment of public schools teachers. AB - Programs geared towards the occupational health of public workers, that include the prevention of moral harassment, have been created in Santa Catarina. Any institution identified for its poor records in regards to moral harassment will end up having its image tainted before society at large. This is due to its use of arbitrary and embarrassing means for accomplishing everyday tasks. This article aims to consider Workplace Psychological Harassment (WPH), its risks and implications for the health of public workers. The methodology chosen was a teacher's case study, which consisted of document research, interviews, anamnesis and observation, all in order to relate both theory and practice. The results indicate that WPH is a complex phenomenon, which can be studied in a variety of ways. WPH risks the biopsychosocial health of the worker, causing the deterioration in social-professional relations, illness, and incapacity, as well as higher costs and certain degradation in production. It is difficult to prove incidents and their impact. Nevertheless, this research concluded that WPH has harmful consequences for the physical and mental health of workers, and is in the ergonomic field, since part of this profession's role is to seek understanding of work in order to reorganize it. PMID- 22317011 TI - The 'urge to move' on body supports. AB - It is well known that people that sit or lie down for prolonged periods change their posture on a regular basis. Even when people are asleep on average 20-40 postural can be observed during an 8 hours period of night rest. One of the reasons that can be found in literature for this 'urge to move' is that these movements are necessary to persevere the blood flow in the tissue. The aim of this paper is to study the relation between tissue perfusion and pressure on the tissue and frequency of the load cycle. Each subject is subjected to a treatment scheme that varies in pressure and frequency of the load on the tissue. The pressure levels that are used are 2.7 kPa, 4.0 kPa and 5.3 kPa and the frequency levels that are used are loading/unloading at intervals of 5 min., 10 min., 15 min. Statistics shows that for 2.7 kPa there is a significant reduction of blood flow between time intervals of 5 min. and 10 min. (P=0.028), and 5 min. and 15 min. (p=0.009). Statistics also shows that there is no significant reduction in blood flow at the time interval of 10 minutes, for every level of pressure. This series of measurements seems to suggest that at the time interval of 10 minutes for every level of pressure the blood flow does not decrease compared to the start situation. PMID- 22317012 TI - Kinematic analysis of post office employees' workstations. AB - This study analyzed a post office clerk's tasks, comparing two workstation models. The clerk was facing the client in one, and seated at 45 degrees to the counter in the other. We analyzed the most frequent tasks and those presenting the most critical points: 1) payment of a postal order; 2) accepting a registered letter, breaking them down into subtasks. We used an optoelectronic system for kinematic analysis, and calculated the range of motion of the trunk and arms in the three spatial planes. The 45( position required less torsion of the trunk and head when using the printer, placed to the left of the employee. A larger worktop improved the workstation, leaving more room for equipment and allowing the worker to sit frontally to the monitor. However, this solution involved a shorter distance between the worker and the client with longer extension of the shoulder and elbow and less trunk flexion. These findings suggested a modification in the layout that shortens the distance between the worker and client. PMID- 22317013 TI - Accessibility of sports facilities for persons with reduced mobility and assessment of their motivation for practice. AB - This study aims to create awareness, both within the scientific community and among providers of sports facilities, for individuals with impaired or reduced mobility, promoting the development of technical solutions that allow greater autonomy and social integration of people with disabilities. The purpose of this work is, on the one hand, to evaluate the accessibility of sports facilities for people with reduced mobility and, on the other hand, to investigate why this user group has such low rates of participation in sporting activities. Firstly, using the Portuguese norms and legislation transcribed from European Community directives, a check list was created comprising all the items that sports facilities should abide by in order to provide accessibility and safety to people with reduced mobility. Another questionnaire was designed aimed at this user group, with questions pertaining to their desire and ability to use sports facilities. This questionnaire was distributed in Portugal, in the greater metropolitan area of Porto, to users of Rehabilitation Centres and Physiotherapy Clinics. The results obtained from the check-list showed the compliances and non compliances of the respective sports facilities, proving that many barriers preventing the participation of people with reduced mobility still exist. Twenty four people with permanent impairment of the lower extremities (paraplegia) answered the questionnaire pertaining to the desire and ability to perform physical activity. Two individuals (8%) had sporting activities available to them in their area of residence and only five (21%) performed any physical activity. The main reason given for not taking part in any activity was the lack of adapted sports facilities. All the participants felt that taking part in sports is beneficial. The benefits stated were: general well-being and development of the psychomotor component (e.g. coordination, balance, body posture), of physical condition (e.g. strength, resistance, flexibility) and social integration and quality of life. Besides wellbeing, they also mentioned social interaction, a way of occupying their time and an escape from the routine as the main motives for which they would like to take up physical exercise. PMID- 22317014 TI - Hand therapy and ergonomics: integration of approaches in vocational rehabilitation and promotion of decent work in Brazil. AB - Among the indicators of Decent Work in Brazil, the one referring to the "Safe Working Environment" was the only which had no improvement in the time series analyzed by the International Labor Organisation. There is an increased number of accidents with significant economic and social impacts. Given that many of these accidents involve the hands and cause functional sequels, this paper presents an integration between the approaches of Hand Therapy and Ergonomics in order to facilitate the process of rehabilitation and reintegration, as well as acting to prevent further accidents, thus contributing to the promotion of Decent Work in the country, particularly with regard to safety and health at work and equal opportunities. PMID- 22317015 TI - Effects of wearing a pressure redistribution belt while lying in a hospital bed. AB - Bedsores (ulcers) are caused by multiple factors which include, but are not limited to; pressure, shear force, friction, temperature, age and medication. Specialised support services, such as specialised mattresses, sheepskin coverings etc., are thought to decrease or relieve pressure, resulting in a lowering of pressure ulcer incidence [3]. The primary aim of this study was to compare the upper/central body pressure distribution between normal lying in a hospital bed versus the use of a pressure redistribution belt. The study involved 16 healthy voluntary subjects lying on a hospital bed with and without wearing the belt. Results showed that the use of a pressure redistribution belt results in reduced pressure peaks and prevents the pressure from increasing over time. PMID- 22317016 TI - Design of an ergonomic ultrasound system: accommodation of user anthropometrics. AB - Long-term use of medical imaging devices requires significant improvements to the user experience. One factor that impact upon such experience is whether the device is ergonomically built, ecologically designed, and leverages the current medical practice. In this research, we took a holistic and systematic approach to design an effective and biomechanically-fit ultrasound system. Research methods from behavior science (e.g., contextual inquiry, pseudo experiments) had been adopted to involve the users (sonographers) early in the design process. The end results - product design guideline for a cart type ultrasound system and control panel layout - were reviewed by the users and adjusted so that the design is within the range of an acceptable learning curve while maintaining innovativeness, a differentiated value over competitor's ultrasound devices. PMID- 22317017 TI - Weight gain in relation to night work among nurses. AB - OBJECTIVE: To investigate the relationship between working at night and increased body weight in nursing. In addition, we evaluated the differences in the proportion of variables sociodemographic, work and health, according to the work shift and their association with body mass index. METHODS: Based on questionnaires, we obtained data from 446 nursing professionals about aspects of their job, health and lifestyle. We performed linear and logistic regression analysis. RESULTS: Working at night is associated with a weight gain greater than (beta=0.24 kg/m2) working during the day (beta=0.15 kg/m2), as well as with aging (beta=0.16 kg/m2) and duration of working in nursing (beta=0.18 kg/m2). Night workers have a higher educational level, have been working for more years in nursing and also in the current shift, do not have diabetes and have reported longer sleep than day workers. There are also a higher number of smokers among the night workers than day workers. Logistic regression analysis also showed the more time to work in nursing and as an assistant was more likely to develop overweight/obesity. CONCLUSION: Working at the night contributes to more weight gain than the day shift, aging and duration of working in nursing. PMID- 22317018 TI - Relationship between exposure to cement and the incidence of respiratory diseases in children: a preventive perspective. AB - Respiratory disease in childhood is a factor of concern to health professionals, resulting in a primary determinant of lung function in adulthood. Studies indicate that people placed in areas with established industries, are exposed to pollutants from many industrial processes, thus increasing the risk of diseases. The aim was to examine the connection between exposure to cement and the incidence of respiratory diseases in the Jardins Community. It was a field study, descriptive, conducted in a community in the city of Cabedelo- PB, and result in a qualitative-quantitative approach. The sample comprised 51 children aged between 1 to 12 years who have symptoms or diagnosis of respiratory disease. The survey data was obtained by applying a semistructured interview, and analysed using chi-square, MacNemar and Mann-Whitney tests for statistical analysis. A high number of complaints about environmental pollution, small houses and subdued, lack of paving and sanitation, a high frequency of respiratory symptoms and especially the occurrence of the onset of symptoms after arrival in the community were found. There is a correlation between environmental exposure and the incidence of respiratory diseases in children; therefore the community requires specific actions to reduce the exposure. PMID- 22317019 TI - Quick Exposure Check (QEC): a cross-cultural adaptation into Brazilian Portuguese. AB - Most instruments used by occupational safety and health professionals have been originally developed in English. Cross-cultural adaptation enables the use of these instruments in other countries, cultures and languages in countries like Brazil, where the official language is not English. This methodology ensures that the translation process includes the cultural and linguistic equivalence between the original instrument and the translated version. Therefore, this study aimed to translate and cross-culturally adapt the instrument Quick Exposure Check (QEC) into Brazilian-Portuguese. The process of cross-cultural adaptation followed the steps of translation, synthesis, back-translation, expert committee review and pretesting. The final questionnaire was pretested by two raters in 40 workers employed in an expedition of knitting and textile industry. All versions resulting from the translation process (T1, T2) and back-translation (BT1, BT2) showed good agreement. During the pre-test was not presented any difficulty in understanding or completing the instrument adapted QEC for Brazilian language. PMID- 22317020 TI - Moral harassment at work model and inability. AB - Moral Harassment at Work (MHW) is considered a recurrent practice of humiliation, mockery, isolation, persecution and psychological torture. Its results go beyond the worker private life: represent financial loss, affects the work, the organization, the productivity and the society. This article aims to develop a model of MHW, which characterizes the main components of the phenomenon and their nexus with the inability to work. For this, the Literature field is consulted, in order to identify systematically, the MHW components and their risky factors. The results showed a multifaceted model which demonstrates: the aggressor/victim and the configuration of the Moral Harassment at Work causes. The management of the degraded work. The characteristic features of the inability to work, caused on the victim. The MHW modalities and as a final product, the integration among these components. It is expected that this model can help the Ergonomist comprehending this phenomenon and contribute on the creation of some strategies of prevention on the workplace. It is concluded that the removal or minimization of this occupational risks requires some changes on the job organization, on the people's behaviour, the leadership styles, on the humanization of the social labor relationship and on the coping this problem. PMID- 22317021 TI - Design and ergonomics of package inserts of drugs in Brazil: a reality in construction. AB - This research deals with the design of leaflets of medicines, evidencing the problems resulting from the lack of Brazilian normalization to promote the use of the graphical representation of instructional texts warnings. It approaches studies related to the effectiveness and efficiency of information systems, highlighting the semiotics and the cultural and informational ergonomics. The analysis of the context uses as method, an analytical study on selected warnings of thirty leaflets of medicines, followed by interviews lead with the public managers involved with the regulation of the pharmaceutical companies, and two experiments with users performed in city of Recife, in State of Pernambuco: one aiming at to identify how they interact with the leaflets of medicines, and the second one testing their understanding concerning standardized illustrations in the United States and the South Africa. The results show the need for improvements in presentation and graphic representation of leaflets of medicines, powering them to the role of communication, to ensure the consumption of medicine safely by its users. The conclusion congregates parameters and recommendations for the graphic representation of warnings in leaflets of medicines in Brazil. PMID- 22317022 TI - How user diversity and country of origin impact the readiness to adopt E-health technologies: an intercultural comparison. AB - In recent years, due to the demographical change and the resulting overload of healthcare systems, there has been an increasing interest focusing on the global proliferation of assistive medical technologies (=E-health) in home environments. The present study examines how users' diversity influences the readiness to adopt novel medical technologies, comparing users' attitudes in terms of perceived advantages and disadvantages in three technically and culturally different countries: Germany, Poland and Turkey. This investigation also intended to verify if acceptance of information and communication technologies is associated with the sensitive acceptance of E-health. Results revealed overall a considerably higher motivation to use medical technology compared to perceived barriers, with Polish users more willing to use E-health, higher than German or Turkish ones. Older participants showed a highly positive attitude, comparable to young and middle-aged respondents' receptiveness, differing from the latter in terms of greater appreciation of the advantage of higher independency when being supported by medical technology. With respect to gender, woman showed higher motivation to use E-health technology than men, although utilization barriers were not gendered. Following these results, an unconditional transfer of acceptance from information and communication to medical technology is not justified. PMID- 22317023 TI - Using walker during walking: a pilot study for health elder. AB - Walker operation completely relies on the walker handle, however most marketed walkers possess two horizontal handles. Several researchers have suggested that horizontal handles might lead to wrist injury. Therefore, the purpose of this study is to assess the relevant design aspects of walker for elderly people. 28 elders participated in this study; when the experiment was started, subject walked on the tile for 3 meter distance twice by using walker. Data for analysis were selected at the corresponding wrist deviation and vertical force. The results showed that during walker using, the mean wrist deviation was greater than zero. The largest vertical force is significantly larger than the smallest one, and different wrist deviation occurred at three phases, the largest wrist deviation while raising walker is larger than the smallest one, however, no significant different was found between the largest and smallest wrist deviation while pressing walker. No significant correlation occurred between weight and wrist deviation. The correlation between weight and vertical force was significantly positive. With wrist deviation walker use may cause injury to upper limb, however wrists remain in a neutral position during hand movement to prevent damage. The findings of this study should improve the design of walker handles to reduce the wrist deviations of users. PMID- 22317024 TI - An office chair to influence the sitting behavior of office workers. AB - Since the introduction of ergonomic guidelines in the design of office chairs, a lot of effort has been put in designing these office chairs accordingly. Because these features all have to be adjusted in different ways (mostly a knob underneath the seat surface), and because every office chair offers different solutions, often users do not use all of the adjustments, and thus do not use the office chair an the optimal ergonomic way. The aim of this paper is to study the influence of feedback on sitting habits of office workers in a field test during 4 weeks. 40 office workers were selected for this test (13 male, 27 female). They were divided in three groups. A control group, a group that received a sitting instruction and a group that received sitting instruction and feedback on their posture every hour that they sit. The results show that there is an effect in average increase in basic posture on both the group that received instruction and the group that received feedback. This effect decreases over time. There was no effect in the control group. PMID- 22317025 TI - A low cost technique to evaluate usable product for small manufacturing companies: a case study on Garcia robot. AB - A usability evaluation technique to evaluate user interfaces is introduces. The technique is effective and affordable for small manufacturing companies. By using this technique, an integration of users' feedbacks and some usability concepts, a product can be 3 times easier to use among potential users and more than 5 times easier to use among motivated users. In addition, the technique can be implemented with the company's employees as participants. PMID- 22317026 TI - Social responsibility and work conditions: building a reference label, Demarche T(r). AB - Corporate Social Responsibility (CSR) is now considered in large and global companies and the recent publication of the ISO 26000 standard clarifies the targets. Based on our consultancy's experience for fifteen years in ergonomics mainly in French small and medium enterprises, we developed a label to coax and value efforts of companies in dealing with health and safety at the work place as required by ISO 26000 paragraph 6.4. The formal approach of ISO describes what should be achieved but gives no cue on how actual conditions of work should be improved. The label, called Demarche T (ie Process W where W stands for work) aims the management of work conditions as a process, giving visibility and credit to companies for their continuous involvement in the matter. We describe the items and processes that are part of our assessment. We first conduct an ergonomic diagnosis including the analysis of records on health, physical and psychological well-being, observations at the workplace and interviews with the workers. This diagnosis is followed by recommendations. The fulfillment of these is assessed yearly. Items under assessment include: - ergonomics, health and safety in the companies statements and their impact in actual project management; - relations with workers through the committee for health and safety; - actual results on health, safety and work conditions. On a local level, we give the companies passing the label a competitive edge in recruiting better candidates motivated by good work conditions, and help them fulfill ISO 26000 requirements, an increasingly decisive advantage to benefit from public regional and European support. Our paper describes the diagnosis and follow-up process. PMID- 22317027 TI - A study of material composition disclosure practices in green footwear products. AB - This work is based on the study of pioneering sustainable product development initiatives, and the analysis was guided by the cradle-to-cradle concept, which sees the waste of a given process as raw material for another, just like it happens in nature. Several studies on human factors have focused on factory conditions and workers dealing with product assembly. This research, however, relates more to consumer behavior, product use and end-of-life. The purchase of more environmentally- friendly products, in particular, is heavily influenced by the information made available by the companies. In this scenario, this article discusses three early but notable efforts on green product development, focusing on the disclosure practices adopted by the companies regarding the composition of their products. Research and data collection has focused on the footwear industry, whose products satisfy a basic human need and are ubiquitous worldwide. The use of hazardous materials and chemicals in shoe manufacturing, particularly the use of chromium - a highly toxic element - in addition to toxic solvents and adhesives and non-recyclable synthetic materials can pose serious risks to human health and the environment, even though the consumer usually is not aware of all the relevant characteristics of this kind of product. PMID- 22317028 TI - Designing for multiple global user populations: increasing resource allocation efficiency for greater sustainability. AB - This paper proposes a method to identify opportunities for increasing the efficiency of raw material allocation decisions for products that are simultaneously targeted at multiple user populations around the world. The values of 24 body measures at certain key percentiles were used to estimate the best fitting anthropometric distributions for female and male adults in nine national populations, which were selected to represent the diverse target markets multinational companies must design for. These distributions were then used to synthesize body measure data for combined populations with a 1:1 female:male ratio. An anthropometric range metric (ARM) was proposed for assessing the variation of these body measures across the populations. At any percentile, ARM values were calculated as the percentage difference between the highest and lowest anthropometric values across the considered user populations. Based on their magnitudes, plots of ARM values computed between the 1st and 99 th percentiles for each body measure were grouped into low, medium, and high categories. This classification of body measures was proposed as a means of selecting the most suitable strategies for designing raw material-efficient products. The findings in this study and the contributions of subsequent work along these lines are expected to help achieve greater efficiencies in resource allocation in global product development. PMID- 22317029 TI - The usability of a product can be an ally of sustainability. AB - Few steps like turning off the tap while brushing your teeth, turn off the lights when leaving a room, recycle waste or using recycling bags are considered sustainable attitudes. Sustainable development is one that meets the needs of the present generation without compromising the future generations and it doesn't deplete resources for the future. Consume with conscious is a sustainable habit and usability of products contributes to this. The goal of this paper is to prove that the usability of software contributes positivity or negativity for sustainability. By calculating the amount of electrical power dissipated by an electronic device, you can discover the amount of energy lost by it, and consequently, to relate this quantity with the amount charged by the concessionaire for each kWh of energy used. It was concluded that a software with low usability cause users to lose a lot of time interacting with it and thus spend more energy and money that goes against the concept of sustainability. PMID- 22317030 TI - Cooking behaviours: a user observation study to understand energy use and motivate savings. AB - Electric cookers are one of the highest energy consuming domestic appliances, and there are several aspects that can influence the amount of energy used when preparing a meal. Appliance characteristics are shown to influence consumption, but human factors play an important role in the overall electricity usage. A user observation study was conducted among university students to understand how they use electric cookers. They were asked to perform a specific cooking task, and the electricity usage was measured. Participants' behaviours were analysed and compared with a set of energy saving techniques. Appliance characteristics that influenced how students use energy were also investigated. The results show that users performed the task in several different ways, presenting diverse energy consumption, the average being 3 times above the necessary to complete the task. This information is now informing the design of interventions to motivate people to change their behaviours whilst cooking. PMID- 22317031 TI - The importance of ergonomics to sustainability throughout a building's life cycle. AB - Protecting and conserving environmental resources is a global concern. Over the past decade, a number of certification processes have emerged to help designers and operators of buildings assess the potential impact of a building on the environment. Certifications such as the Leadership in Energy and Environmental Design (LEED) consider the environmental impact through the lifecycle of a building, but may not be considering the people that construct and utilize it. It is important to remember the human factor. Considering the human factor throughout the lifecycle is crucial to ensure individuals are protected during construction and in operation in the built environment. The paper highlights how ergonomics can be integrated into the life cycle of a building to promote sustainability goals for both the human factor and the environment. A case study approach will be used to illustrate how ergonomics was integrated into a LEED renovation and expanded into its daily operations on a large university campus.. PMID- 22317032 TI - Ergoecology: evolution and challenges. AB - This work details the conceptual and methodological evolution of 'Ergoecology' and its relationship to certain comparable disciplinary proposals and standards, with a view to making its current status known and fostering discussion and development of it in a broader context. 'Ergoecology' is a discipline which relates the ergonomic system to 'environmental factors', stressing the relationships between ecological-geographical aspects and human activities. After analyzing previously-developed and partially-validated methods, strengths are established, together with areas where there is room for improvement, based on conceptual validity. The objectives, principles, and premises of 'Ergoecology' will be revised and therefore it will be able to be compared with other disciplinary and regulatory developments. Finally, new concepts and notions are proposed, together with basic principles and axioms that will enable 'Ergoecology' to advance in both, the theoretical and the practical dimensions, leaving the door open to be disseminated and applied. PMID- 22317033 TI - The human component of sustainability: a study for assessing "human performances" of energy efficient construction blocks. AB - This paper presents an applied research aimed at understanding the relevance and the applicability of human related criteria in sustainability assessment of construction materials. Under a theoretical perspective, human factors consideration is strongly encouraged by building sustainability assessment methods, but the practice demonstrates that current models for building sustainability assessment neglect ergonomic issues, especially those ones concerning the construction phase. The study starts from the observation that new construction techniques for high energy efficient external walls are characterized by elements generally heavier and bigger than traditional materials. In this case, high sustainability performances connected with energy saving could be reached only consuming high, and then not very much sustainable, human efforts during setting-up operations. The paper illustrates a practical approach for encompassing human factors in sustainability assessment of four block types for energy efficient external walls. Research steps, from block selections to bricklaying task analysis, human factors indicators and metrics formulation, data gathering and final assessment are going to be presented. Finally, open issues and further possible generalizations from the particular case study will be discussed. PMID- 22317034 TI - User-centered ecotourism development. AB - The transfer of knowledge in an ecotourism project is never a one-way affair. An approach connected to bottom-up development is the submersion into another culture, while creating a new organizational structure. For co-creation, patterns that are often latent, such as leadership roles, the association with business, or even the color of education can be revealed by carefully facilitated brainstorms or workshops. Especially in countries with a different hierarchical structure, such as Indonesia compared to Holland, a careful analysis is needed before starting cooperation. Although a case is only a temporary view on a situation and not a guarantee for a truly sustainable system, the bottom-up approach tested has interesting starting points for an ecotourism system. Two cases were conducted in Bali, Indonesia, which resulted in guidelines on how to approach user-centered ecotourism development. PMID- 22317035 TI - A broader consideration of human factor to enhance sustainable building design. AB - The link between ergonomic/human factor and sustainability seems to be clearly evidenced mainly in relation to social dimension of sustainability, in order to contribute to assure corporate social responsibility and global value creation. But the will to establish an equilibrated connection among used resources in human activities, supported by the sustainability perspective, evidences that the contribution of ergonomics/human factors can be effectively enlarged to other aspects, especially in relation to building design. In fact a sustainable building is meant to be a building that contributes, through its characteristics and attribute, to a sustainable development by assuring, in the same time, a decrease of resources use and environmental impact and an increase of health, safety and comfort of the occupants. The purpose of this paper is to analyze in a broader sense the contribution of ergonomic/human factor to design of sustainable building, focusing how ergonomics principles, methodology and techniques can improve building design, enhancing its sustainability performance during all phases of building lifecycle. PMID- 22317036 TI - Sustainability and cities: a proposal for implementation of a sustainable town. AB - This article presents a literature review on the concept of sustainability applied to cities and a proposal for transforming a town in the south of Brazil into a sustainable town. Improvements in energy, sanitation, waste and water conditions, as well as food, clothing, education and jobs generation were considered to enhance the citizen's quality of life and environmental protection. PMID- 22317037 TI - VLT: a sustainable solution to urban mobility, in Joao Pessoa-PB. AB - The changes happen quickly in today's world, simultaneously interacting with technological advances in the sciences and new paradigms socio-political and economic, in search of a sustainable future and a present with emergency strategies for the preservation of humanity and the planet "Earth ". Currently, the mobility of people in the intra-urban space is being threatened by congestion, pollution resulting from the appreciation of the culture of personal transport and the precariousness of public transportation. In the city of Joao Pessoa (PB), the subject of this finding for these disorders. Workers suffer the consequences of daily stress takes to access home-work, difficulty in arriving at the right time to the workplace and adverse reactions caused by pollution. The VLT (Light Rail Vehicle) has been presented as a viable solution to the problems of public transport, with several experiments that can be seen as positive in the world. This work involves the implementation of a public transport system based on VLT Corridor along the Avenue Dom Pedro II, in Joao Pessoa (PB), aiming to acquire a good transport network for use of the population, reduce the number of vehicles on process, minimize pollution and optimize urban mobility. PMID- 22317038 TI - Design and the global and human wellbeing. AB - This paper approaches the challenge of considering the principles of sustainable development in the conception of products, services or systems in a specific territory, though inserted in a globalized world. The reflection takes place by crosschecking the information gathered through bibliographical research on the following themes: wellbeing, design, and the local versus global relation. Thus, the strategy of analysis adopted comprehends the triangulation of information for further comparison of the survey and discussion of the data obtained. This paper results in a set of reflections on the interactions between human beings and their territories, towards new conceptions oriented to a more sustainable future. PMID- 22317039 TI - Environmental management performance for Brazilian industrials: measuring with the item response theory. AB - Growing challenges with respect to preserving the environment have forced changes in company operational structures. Thus, the objective of this article is to measure the evidence of Environmental Management using the Item Response Theory, based on website analysis from Brazilian industrial companies from sectors defined through the scope of the research. This is a qualitative, exploratory, and descriptive study related to an information collection and analysis instrument. The general view of the research problem with respect to the phenomenon under study in based on multi-case studies, with the methodological outline based on the theoretical reference used. Primary data was gathered from 270 company websites from 7 different Brazilian sectors and led to the creation of 26 items approved by environmental specialists. The results were attained with the measuring of Environmental Management evidence via the Item Response Theory, providing a clear order of the items involved based on each item's level of difficulty, quality, and propriety. This permitted the measurement of each item's quality and propriety, as well as that of the respondents, placing them on the same analysis scale. Increasing the number of items and companies involved is suggested fEor future research in order to permit broader sector analysis. PMID- 22317040 TI - Adaptive information design for outdoor augmented reality. AB - Augmented Reality focuses on the enrichment of the user's natural field of view by consistent integration of text, symbols and interactive three-dimensional objects in real time. Placing virtual objects directly into the user's view in a natural context empowers highly dynamic applications. On the other hand, this necessitates deliberate choice of information design and density, in particular for deployment in hazardous environments like military combat scenarios. As the amount of information needed is not foreseeable and strongly depends on the individual mission, an appropriate system must offer adequate adaptation capabilities. The paper presents a prototypical, vehicle-mountable Augmented Reality vision system, designed for enhancing situation awareness in stressful urban warfare scenarios. Tracking, as one of the most crucial challenges for outdoor Augmented Reality, is accomplished by means of a Differential-GPS approach while the type of display to attach can be modified, ranging from ocular displays to standard LCD mini-screens. The overall concept also includes envisioning of own troops (blue forces), for which a multi-sensor tracking approach has been chosen. As a main feature, the system allows switching between different information categories, focusing on friendly, hostile, unidentified or neutral data. Results of an empirical study on the superiority of an in-view navigation cue approach conclude the paper. PMID- 22317041 TI - Comparing two types of navigational interfaces for Virtual Reality. AB - Previous studies suggest significant differences between navigating virtual environments in a life-like walking manner (i.e., using treadmills or walk-in place techniques) and virtual navigation (i.e., flying while really standing). The latter option, which usually involves hand-centric devices (e.g., joysticks), is the most common in Virtual Reality-based studies, mostly due to low costs, less space and technology demands. However, recently, new interaction devices, originally conceived for videogames have become available offering interesting potentialities for research. This study aimed to explore the potentialities of the Nintendo Wii Balance Board as a navigation interface in a Virtual Environment presented in an immersive Virtual Reality system. Comparing participants' performance while engaged in a simulated emergency egress allows determining the adequacy of such alternative navigation interface on the basis of empirical results. Forty university students participated in this study. Results show that participants were more efficient when performing navigation tasks using the Joystick than with the Balance Board. However there were no significantly differences in the behavioral compliance with exit signs. Therefore, this study suggests that, at least for tasks similar to the studied, the Balance Board have good potentiality to be used as a navigation interface for Virtual Reality systems. PMID- 22317042 TI - On the effect of free vs. restricted interaction during the exploration of virtual environments. AB - Exploration of a Virtual Environment (VE) might vary as well in applied technology as in the conceptual design. A conceptual difference of exploring style and navigation type relates to the degree of freedom a user possesses. It ranges from completely unrestricted to completely restricted navigation. To assess the impact of different exploration styles, an experiment was carried out. Four different styles were compared in a large-scale VE. The navigation of the participants was either free or restricted in various levels concerning motion and viewing direction. During the exploration, the participants memorized the location of flags, which represented special events at these locations. The participant's task was to memorize position and color of the flags. Subsequently, they marked the positions and colors of the flags in a map of the scene. The performance in this task was captured, as well as data about their amount of experienced simulator sickness and subjective workload. Additionally, balancing tests were administered to investigate in an objective measurement of simulator sickness. Each condition showed the same achievement in the memorizing task and the subjective workload. Furthermore, the measured high variance in simulator sickness symptoms overrode other effects. In the balancing tests a basic influence of exposure with VE was found. However, subsequent interviews with the participants showed that the personal impression of the efficiency of exploration method was highly individual. By finding and matching exploration methods to individual persons, benefit by using Virtual environments could be enhanced. PMID- 22317043 TI - Evaluating the iterative development of VR/AR human factors tools for manual work. AB - This paper outlines the approach taken to iteratively evaluate a set of VR/AR (virtual reality / augmented reality) applications for five different manual-work applications - terrestrial spacecraft assembly, assembly-line design, remote maintenance of trains, maintenance of nuclear reactors, and large-machine assembly process design - and examines the evaluation data for evidence of the effectiveness of the evaluation framework as well as the benefits to the development process of feedback from iterative evaluation. ManuVAR is an EU funded research project that is working to develop an innovative technology platform and a framework to support high-value, high-knowledge manual work throughout the product lifecycle. The results of this study demonstrate the iterative improvements reached throughout the design cycles, observable through the trending of the quantitative results from three successive trials of the applications and the investigation of the qualitative interview findings. The paper discusses the limitations of evaluation in complex, multi-disciplinary development projects and finds evidence of the effectiveness of the use of the particular set of complementary evaluation methods incorporating a common inquiry structure used for the evaluation - particularly in facilitating triangulation of the data. PMID- 22317044 TI - Preparative study regarding the implementation of a muscular fatigue model in a virtual task simulator. AB - Muscle fatigue is considered as one of the major risk factors for developing musculoskeletal disorders. The aim of this project was to select an adequate fatigue assessment model for an implementation in Dassault Systemes digital human modeling software. A review of existing MET models has been done resulting in a decision to use the extended Ma's model (2010). In this project, only shoulder and elbow joints have been tested and more subjects will be necessary for further validation. The model has been compared to several endurance time (ET) static studies. Two dynamic experiments were also performed by two different subjects. The results showed that because of the inter-individual variability, a simple prediction curve or value, can't well predict individual measured ET (or task failure). There is a need for a chart representation which also shows standard deviation (SD) range. Considering the SD range, the results were included in the prediction. Thus, this range may help the human factors expert to nuance the prediction results while considering environment factors and some realities specific to the industry. PMID- 22317045 TI - Patterns of correlation between vehicle occupant seat pressure and anthropometry. AB - Seat pressure is known as a major factor of seat comfort in vehicles. In passenger vehicles, there is lacking research into the seat comfort of rear seat occupants. As accurate seat pressure measurement requires significant effort, simulation of seat pressure is evolving as a preferred method. However, analytic methods are based on complex finite element modeling and therefore are time consuming and involve high investment. Based on accurate anthropometric measurements of 64 male subjects and outboard rear seat pressure measurements in three different passenger vehicles, this study investigates if a set of parameters derived from seat pressure mapping are sensitive enough to differentiate between different seats and whether they correlate with anthropometry in linear models. In addition to the pressure map analysis, H Points were measured with a coordinate measurement system based on palpated body landmarks and the range of H-Point locations in the three seats is provided. It was found that for the cushion, cushion contact area and cushion front area/force could be modeled by subject anthropometry, while only seatback contact area could be modeled based on anthropometry for all three vehicles. Major differences were found between the vehicles for other parameters. PMID- 22317046 TI - New enhancements and validation of force based posture and discomfort predictions. AB - Many digital human models provide the crucial method to calculate postures in virtual environments. Traditionally these methods refer to experiments and make use of statistical modeling. They provide sufficient results in their specialized domain, but cannot be used in general applications. In addition they do not consider important design aspects as forces and discomfort. Hence a new force based approach has been introduced in order to overcome these shortcomings. Based on biomechanical models of active maximal and passive receding joint torques, a mechanical optimization generates static stable postures and related discomfort ratings. The results were promising, but showed some model deficiencies and were not validated in detail. The present paper continues this work and provides necessary model enhancements. Finally the new prediction models are validated on real experiments. The validation results are presented and discussed regarding to usability aspects and future development work. PMID- 22317047 TI - DHM in human-centered product design: a case-study on public transport vehicle. AB - The goal of this paper is to present the advantages on the use of 3D Digital Human Models (DHM) on the design of public transport vehicles. In this case, the subjects were scanned using the WBX Cyberware 3D Whole Body Scanner, with functional and daily postures according to the use of public transportation and some especial cases, such as a mother with her offspring or a business man with his valise, so the volume of the person would be taken in consideration. A data collection was created to simulate several situations of the daily use of the vehicle. PMID- 22317048 TI - DHM simulation in virtual environments: a case-study on control room design. AB - This paper will present the workflow developed for the application of serious games in the design of complex cooperative work settings. The project was based on ergonomic studies and development of a control room among participative design process. Our main concerns were the 3D human virtual representation acquired from 3D scanning, human interaction, workspace layout and equipment designed considering ergonomics standards. Using Unity3D platform to design the virtual environment, the virtual human model can be controlled by users on dynamic scenario in order to evaluate the new work settings and simulate work activities. The results obtained showed that this virtual technology can drastically change the design process by improving the level of interaction between final users and, managers and human factors team. PMID- 22317049 TI - Digital test assembly of truck parts with the IMMA-tool--an illustrative case. AB - Several digital human modelling (DHM) tools have been developed for simulation and visualisation of human postures and motions. In 2010 the DHM tool IMMA (Intelligently Moving Manikins) was introduced as a DHM tool that uses advanced path planning techniques to generate collision free and biomechanically acceptable motions for digital human models (as well as parts) in complex assembly situations. The aim of the paper is to illustrate how the IPS/IMMA tool is used at Scania CV AB in a digital test assembly process, and to compare the tool with other DHM tools on the market. The illustrated case of using the IMMA tool, here combined with the path planner tool IPS, indicates that the tool is promising. The major strengths of the tool are its user friendly interface, the motion generation algorithms, the batch simulation of manikins and the ergonomics assessment methods that consider time. PMID- 22317050 TI - Features and limitations of digital human models--a new German guideline. AB - In 2008 the Association of German Engineers (VDI) published the first part of the VDI 4499 guideline for methods and tools for the digital factory. Part 1 of this guideline deals with the fundamentals of the system and will be expanded by the addition of further parts on specific topics within the digital factory. Soon to be published is Part 4 which covers human models as tools of the digital factory. It describes the state of the art of current digital human models with regards to the methods and procedures implemented in German speaking countries. The structure of this part of the guideline is based on the different sections of engineering mechanics and outlines the opportunities for ergonomic assessments and the evaluation of work systems. During the writing of the guideline, the restrictions of the existing procedures also became evident thus showing the requirement for further development of such procedures. This is illustrated in this paper using examples from commercial software systems. PMID- 22317051 TI - Elbow torque ellipses: investigation of the mutual influences of rotation, flexion, and extension torques. AB - Most strength tests are restricted to measuring joint torques only in main directions like flexion or pronation. However, for an advanced strength prediction model, information about maximum possible joint torques in intermediate directions also has to be known. This paper concentrates on obtaining functions for maximum joint torques in arbitrary directions in the elbow. Therefore, isometric joint torque measurements have been conducted with 20 young males applying joint torques in eight different directions in one posture (90 degrees elbow flexion, 0 degrees shoulder flexion, neutral forearm rotation). It turns out that the appearance of the resulting shape can be best predicted using ellipse segments. Furthermore, a standardized ellipse could be obtained for the measurement posture. This helps to predict maximum joint torques in any other direction by knowing only one of the main joint torques. PMID- 22317052 TI - Modeling human-bed interaction: the predictive value of anthropometric models in choosing the correct bed support. AB - The sleep system (i.e. the combination of mattress and bed base) is an important factor of the sleep environment since it allows physical recuperation during sleep by providing proper body support. However, various factors influence the interaction between the human body and the sleep system. Contributing factors include body dimensions, distribution of body weight and stiffness of the sleep system across the mattress surface. During the past decade, the rise of several new bedding technologies has made it increasingly difficult for the consumer to select a proper sleep system. Therefore, this study presents a method to model human-bed interaction in order to objectively predict the ideal sleep system for a particular individual. The proposed method combines a personalized anthropometric model with standardized load-deflection characteristics of mattress and bed base. Results for lateral sleep positions show a root mean square deviation of 11.9 +/- 6.1 mm between modeled spine shapes and validation shapes, derived from 3D surface scans of the back surface. The method showed to be a reliable tool to individually identify the sleep system providing superior support from a variety of possible mattress-bed base combinations. PMID- 22317053 TI - Applications of agent-based simulation for human socio-cultural behavior modeling. AB - Agent-based modeling and simulation (ABMS) has gained wide attention over the past few years. ABMS is a powerful simulation modeling technique that has a number of applications, including applications to real-world business problems [1]. This modeling technique has been used by scientists to analyze complex system-level behavior by simulating the system from the bottom up. The major application of ABMS includes social, political, biology, and economic sciences. This paper provides an overview of ABMS applications with the emphasis on modeling human socio-cultural behavior (HSCB). PMID- 22317054 TI - DHM and serious games: a case-study oil and gas laboratories. AB - The aim in this paper is to present a research on the application of serious games for the design of laboratories in the oil and gas industries. The focus is in human virtual representation acquired from 3D scanning, human interaction, workspace layout and equipment designed considering ergonomics standards. The laboratory studies were simulated in Unity3D platform, which allows the users to control the DHM1 on the dynamic virtual scenario, in order to simulate work activities. This methodology can change the design process by improving the level of interaction between final users, managers and human factor teams. That helps to better visualize future work settings and improve the level of participation between all stakeholders. PMID- 22317055 TI - Skill training in multimodal virtual environments. AB - Multimodal, immersive, virtual reality (VR) techniques open new perspectives for perceptual-motor skill trainers. They also introduce new risks and dangers. This paper describes the benefits and pitfalls of multimodal training and the cognitive building blocks of a multimodal, VR training simulators. PMID- 22317056 TI - The added value of virtual reality technology and force feedback for surgical training simulators. AB - Laparoscopic surgery requires more specialized training of the surgeons than traditional open surgery. The Virtual Basic Laparoscopic Surgical Trainer (VBLaST) is being developed as a virtual version of the Fundamentals of Laparoscopic Skills (FLS) trainer. This study assessed the current haptic and virtual reality (VR) technology of a virtual peg transfer task of the VBLaST, based on the subjective preference of surgeons and their objective task performance measures. Twenty-one surgical residents, fellows and attendings performed a peg-transfer task in the FLS and the VBLaST. Each subject performed 10 trials on each simulator. Results showed that subjects performed significantly better on the FLS than on the VBLaST. Subjects showed a significant learning effect on both simulators, but with an accelerated improvement on the VBLaST. Even so, 81% of the subjects preferred the FLS over the VBLaST for surgical training which could be attributed to the novelty of the VR technology and existing deficiencies of the haptic interface. Despite the subjective preference for the physical simulator, the performance results indicate an added value of VR and haptics in surgical training, which is expected to be demonstrated in more surgically relevant tasks such as suturing and knot-tying. PMID- 22317057 TI - Musculoskeletal disorders: a new approach. AB - Musculoskeletal disorders are still a major problem in daily occupational life. Despite the high incidence rates and important consequences for employees, employers and society, efficient preventive strategies seem to fail in efficiency. The reason may be found in approaching the issue via the classic post factum analysis. The preventive measures are almost not implemented because of the low predictability to be injured which affects the awareness of the problem and the low identification with the improvement proposals. MSD belong to the cumulative diseases which require and anticipating strategy based on early detection of pre-indicating symptoms. PMID- 22317058 TI - Proper manual handling techniques to prevent low back pain, a Cochrane systematic review. AB - Training and provision of assistive devices are considered major interventions to prevent and treat low back pain (LBP) among workers exposed to manual material handling (MMH). To establish the effectiveness of training and provision of assistive devices in preventing and treating LBP an update of a Cochrane literature review was performed to November 2010. Randomised controlled trials (RCTs) and cohort studies with a concurrent control group (CCTs) were included. Nine RCTs (20.101 employees) and nine CCTs (1280 employees) were included for prevention: six more than in the previous version. No study on treatment was found. None of the included RCTs and CCTs provided evidence that training and provision of assistive devices prevented LBP when compared to no intervention or another intervention. PMID- 22317059 TI - Cost-efficient observation of working postures from video recordings--more videos, more observers or more views per observer? AB - In ergonomics, assessing the working postures of an individual by observation is a very common practice. The present study investigated whether monetary resources devoted to an observational study should preferably be invested in collecting many video recordings of the work, or in having several observers estimate postures from available videos multiple times. On the basis of a data set of observed working postures among hairdressers, necessary information in terms of posture variability, observer variability, and costs for recording and observing videos was entered into equations providing the total cost of data collection and the precision (informative value) of the resulting estimates of two variables: percentages time with the arm elevated <15 degrees and >90 degrees. In all 160 data collection strategies, differing with respect to the number of video recordings and the number of repeated observations of each recording, were simulated and compared for cost and precision. For both posture variables, the most cost-efficient strategy for a given budget was to engage 4 observers to look at available video recordings, rather than to have one observer look at more recordings. Since the latter strategy is the more common in ergonomics practice, we recommend reconsidering standard practice in observational posture assessment. PMID- 22317060 TI - The trade-off between meticulousness and methodological variance in normalization of low back EMG. AB - BACKGROUND: Normalization of surface electromyography (EMG) is a common and recommended practice, however this methodological step itself introduces variability to a data set. Quantification of this variance is necessary to correctly interpret overall EMG variability. This information is also paramount to identifying experimentally and clinically relevant normalization task(s) which minimize induced variance yet are time-efficient. PURPOSE: The goal of this study was to quantify the within-day variance of two commonly reported, sub-maximal tasks utilised for low back EMG normalization: one collected with a high degree of meticulousness, and the other collected in a more rapid manner. RESULTS: Only minimal differences were seen between tasks in the magnitude of within-day variance for EMG amplitude at all recording sites, save the right-side L5 location, which showed a significant difference (p=0.020). For trunk posture, within-day variance for the highly meticulous tasks was significantly higher than for the less-meticulous task (p=0.011). CONCLUSION: A less meticulous sub-maximal normalization task performed in a standing position was equal or superior to a more meticulously collected task in terms of kinematic task repeatability and within-day EMG variance. These findings are encouraging for field study applications where meticulous methods are not feasible, and provide a time saving strategy for lab studies. PMID- 22317061 TI - The economic evaluation of a participatory ergonomics programme to prevent low back and neck pain. AB - This study was an economic evaluation conducted alongside a cluster randomised controlled trial with a follow-up of 12 months. The aim was to evaluate the cost effectiveness and cost-benefit of the Stay@Work Participatory Ergonomics programme (PE) compared to a control group (no PE). In total, 37 departments (n=3047 workers) were randomised into either the intervention (PE) or control group (no PE). During a meeting, working groups followed the steps of PE, and composed and prioritized ergonomic measures aimed to prevent low back pain (LBP) and neck pain (NP). Working groups had to implement the ergonomic measures within three months in their department. Cost data included those directly related to LBP and NP. Cost-effectiveness analyses (CEA) and cost-benefit analyses (CBA) were performed. After 12 months, health care costs and costs of productivity losses were higher in the intervention group than in the control group (the mean total cost difference was $/euro$127; 95% CI $/euro$-164 - $/euro$418). From a societal perspective, the CEA showed that PE was not cost-effective compared to control for LBP and NP prevalence, work performance, and sick leave. The CBA from a company perspective showed a monetary loss of $/euro$78 per worker. The PE programme was neither cost-effective nor cost-beneficial on any of the effect measures. PMID- 22317062 TI - Lean production and work-related musculoskeletal disorders: overviews of international and Swedish studies. AB - This paper aimed at summarizing the knowledge of the relationship between Lean and work related musculoskeletal disorders (WMSD), and WMSD risk factors, in manufacturing companies. Literature search processes identified 23 publications studying this, in scientific journals. Eight included measurements of WMSD; three were mostly negative, two showed mixed results, one showed no results and two were mostly positive. Eighteen publications included measurements of WMSD risk factors; seven showed mostly negative results, eight showed mixed results, two showed mostly positive results and one was inconclusive. Three literature reviews were identified, which studied this question; two were mostly negative, while the third was inconclusive. Also, 12 publications of grey literature studying Lean and WMSD risk factors in Swedish organizations were identified; nine showed mixed results, two showed mostly positive results and one showed mostly negative results. Due to the varying quality and study design of the publications, together with the few identified studies, it is difficult to compare them. The context and the implementation also likely affect the results. The general conclusion was that a Lean implementation may increase the risk of WMSD and risk factors for WMSD, if it is not accompanied with an ergonomic intervention. PMID- 22317063 TI - An integrated tool to support engineers for WMSDs risk assessment during the assembly line balancing. AB - This paper wants to present an integrated approach to Line Balancing and Risk Assessment and a Software Tool named ErgoAnalysis that makes it easy to control the whole production process and produces a Risk Index for the actual work tasks in an Assembly Line. Assembly Line Balancing, or simply Line Balancing, is the problem of assigning operations to workstations along an assembly line, in such a way that the assignment be optimal in some sense. Assembly lines are characterized by production constraints and restrictions due to several aspects such as the nature of the product and the flow of orders. To be able to respond effectively to the needs of production, companies need to frequently change the workload and production models. Each manufacturing process might be quite different from another. To optimize very specific operations, assembly line balancing might utilize a number of methods and the Engineer must consider ergonomic constraints, in order to reduce the risk of WMDSs. Risk Assessment may result very expensive because the Engineer must evaluate it at every change. ErgoAnalysis can reduce cost and improve effectiveness in Risk Assessment during the Line Balancing. PMID- 22317064 TI - Handwheel valve operation: assessment of four opening methods in terms of muscle loading, perceived comfort, and efficiency. AB - Injuries due to manual valve handwheel operations are a major concern in the chemical process industry. Manual valves are used to start, stop, and control flow in process lines. The torque required to operate handwheels after the initial "breaking" can vary due to the size, design, and condition of the valve. This study tested four methods of turning the handwheel on a medium-sized gate valve at two different torque requirements (25 Nm and 50 Nm). The methods were compared to each other, in terms of efficiency, subjective ratings of perceived exertion, and electromyography activity of the upper extremity and trunk muscles. The results indicate that different methods and torque requirements are compensated for by the use of different muscles. Also, this use of different muscles, along with the increased mechanical advantage of the wrench, can affect the operator's actual and perceived comfort and efficiency while operating a valve handwheel. PMID- 22317065 TI - Quantitative analysis of repetitive movement as a tool for diagnostic support in ergonomics. AB - OBJECTIVE: To evaluate muscular strain in the upper limbs of workers in a freeze processing plant for poultry by developing a tool for quantitative analysis, yielding a final score, which can provide diagnostic support in legal proceedings. METHODS: The Strain index proposed by Moore & Garg was used to quantify biomechanical aspects of muscular strain, evaluating the intensity and duration of effort, frequency of movement, position of wrist and hand, speed of activity and duration of the task per shift. The index was applied in three critical work-areas in a freeze-processing plant for poultry where the activities of nine workers were analyzed. RESULTS: Absenteeism caused by osteomuscular lesions and mental-health problems reaches 20%. The three work-areas studied are those where the birds' throats are cut, where they are suspended on a conveyor belt and, where they are wrapped. These areas were chosen because they have the highest rates of absenteeism and rotation of workers. The findings identified final scores between 12 and 27, when 7 or more means the maximum risk. CONCLUSION: Defensive strategies developed by workers can reduce biomechanical problems arising from high throughput rates, but are not enough by themselves to allow production to proceed without the occurrence of osteomuscular problems. PMID- 22317066 TI - Old scissors to industrial automation: the impact of technologic evolution on worker's health. AB - To cut a fabric, the professional performs different jobs and among them stands out the cut. The scissors has been the instrument most used for this activity. Over the years, technology has been conquering its space in the textile industry. However, despite the industrial automation able to offer subsidies to answer employment market demands, without appropriate orientation, the worker is exposed to the risks inherent at the job. Ergonomics is a science that search to promote the comfort and well being in consonance with efficacy. Its goals are properly well defined and clearly guide the actions aimed at transforming the working conditions. This study aimed to analyze the activity of cut tissues with a machine by a seamstress and the implications on their body posture. The methodology used was the observation technique and application of the Protocol RULA, where the result obtained was the level 3 and score 5, confirming that "investigations and changes are required soon". Conclude that using the machine to tissue cut should be encouraged, but in conjunction with orientations for improving posture while handling it. It seeks to prevent dysfunction of the musculoskeletal system that prevents employees from performing their work tasks efficiently and productively. PMID- 22317067 TI - Method inventory for assessment of physical activity at VDU workplaces. AB - Physical inactivity and prolonged static work tasks may seriously affect health. There are numerous indications that promoting physical activity (PA) at sedentary workplaces can reduce these health risks. However, PA interventions have so far been documented rarely on the basis of medical parameters. Effects on the PA behavior are often studied only through the methods of subjective self assessment. For this reason an extensive method inventory was developed consisting of objective PA assessment methods and various methods for documenting PA related health outcomes. The developed method inventory has been tested in a pilot intervention study at office workplaces. The current paper presents and discusses a part of the applied inventory. The methods considered here demonstrated several positive intervention effects: intervention subjects were more active, felt better, increased muscle strength and showed improvements in resting heart rate and BMI. Not all data has been analyzed to date, but the preliminary results suggest that most of the investigated methods turned out to be suitable for the documentation of intervention effects. Among the methods for which no effects were found, the question remains whether this is due to a lack of sensitivity of the method or due to aspects related to the study design. PMID- 22317068 TI - Assessing manual lifting tasks based on segment angle interpolations. AB - This study investigates the effects of the number of interpolation points on the prediction accuracy of segment angle trajectory during lifting. Ten participants performed various lifting tasks while a motion tracking system recorded their movements. Two-point through ten-point equal time-spaced segment angles extracted from major segment trajectory data captured by the motion tracking system were used to re-generate the whole body lifting motion by using polynomial and cubic spline interpolation methods. The root mean square error (RMSE) between the reference (motion tracking system) and the estimated (interpolation method) segment angle trajectories were calculated to quantify the prediction accuracy. The results showed that the cubic spline interpolation will yield a smaller RMSE value than one based on the polynomial interpolation. While increasing the number of interpolation points can reduce the RMSE of the estimated segment angle trajectories, there was a diminishing advantage in continuing to add interpolation points. A sensitivity analysis suggests that if the estimation of the segment angles at each interpolation point deviates considerably from the real value, and cannot be controlled at a low level (<10 (), the use of higher number of interpolation points will not improve the estimation accuracy. PMID- 22317069 TI - Prevalence of low back disorders among female workers and biomechanical limits on the handling of load and patients. AB - The purpose of this investigation was to determine the association between prevalence of low back disorders in female workers and biomechanical demands of compressive and shear forces at the lumbar spine. A descriptive, cross-sectional and correlational study was carried out in 11 groups of female workers in the Province of Concepcion. An interview was performed to investigate the prevalence of low back pain. To estimate biomechanical demands on the lumbar spine, it was used the 3DSSPP software. The Pearson correlation coefficient between the prevalence of low back disorders and peak compression force at the lumbar spine was r = (p<0.005). The Spearman correlation coefficient between the prevalence of low back disorders and peak shear force was r = 0.9 (p <0.005). To protect 90% of female workers studied, the limits of compression and shear forces should be at 2.8 kN and 0.3 kN, respectively. These values differ from the recommendations currently used, 3.4 kN for peak compression force and 0.5 kN for peak shear force. PMID- 22317070 TI - Application of discriminant analysis-based model for prediction of risk of low back disorders due to workplace design in industrial jobs. AB - The occupational exposure limits of different risk factors for development of low back disorders (LBDs) have not yet been established. One of the main problems in setting such guidelines is the limited understanding of how different risk factors for LBDs interact in causing injury, since the nature and mechanism of these disorders are relatively unknown phenomena. Industrial ergonomists' role becomes further complicated because the potential risk factors that may contribute towards the onset of LBDs interact in a complex manner, which makes it difficult to discriminate in detail among the jobs that place workers at high or low risk of LBDs. The purpose of this paper was to develop a comparative study between predictions based on the neural network-based model proposed by Zurada, Karwowski & Marras (1997) and a linear discriminant analysis model, for making predictions about industrial jobs according to their potential risk of low back disorders due to workplace design. The results obtained through applying the discriminant analysis-based model proved that it is as effective as the neural network-based model. Moreover, the discriminant analysis-based model proved to be more advantageous regarding cost and time savings for future data gathering. PMID- 22317071 TI - Developing a framework for assessing muscle effort and postures during computer work in the field: the effect of computer activities on neck/shoulder muscle effort and postures. AB - The present study, a part of the PROOF (PRedicting Occupational biomechanics in OFfice workers) study, aimed to determine whether trapezius muscle effort was different across computer activities in a field study of computer workers, and also investigated whether head and shoulder postures were different across computer activities. One hundred twenty participants were measured continuously for two hours each while performing their own computer work. Keyboard activities were associated with the highest intensity of left and right trapezius muscle efforts, and mouse activities were associated with the smallest variability in left and right trapezius muscle efforts. Corresponding trends in head and shoulder postures included that the greatest head flexion and left and right shoulder internal rotation was observed during keyboard activities, and that the smallest variability in head flexion, head lateral tilt, and right shoulder internal rotation was observed during mouse activities. Identifying which muscle efforts and postures are different across computer activities is the first essential step for developing prediction rules for muscle efforts and postures, which can be used to link muscle efforts and postures to musculoskeletal symptoms in epidemiological studies. PMID- 22317072 TI - Evaluation of a personal device in reducing the risk of low back disorders during stooped work. AB - Adoption of the stooped posture in the workplace is widespread throughout the world in agriculture, construction, and mining. This type of posture has been established as a risk factor for developing low back disorders (LBDs). The purpose of this study is to evaluate a personal weight transfer device as a possible intervention to reduce the load on the lumbar spine, thereby reducing the risk of developing LBDs. Eighteen healthy subjects performed stooped posture tasks in a laboratory study designed to simulate harvesting of low-growing crops. Results showed that when wearing the device in the static stooped posture, biceps femoris activity was reduced by 17%, lumbar flexion was reduced by 12%, ankle plantar-flexion increased by 5%, and the lumbar erector spinae of those subjects who did not experience flexion-relaxation of the erector spinae was reduced by 26%. Hip and knee flexion were not significantly altered. Therefore, the device may be beneficial for those with existing LBDs, and who use the stooped posture routinely. PMID- 22317073 TI - Spinal disc hydration status during simulated stooped posture. AB - Stooped work has been shown to be associated with the development of low back disorders, particularly those that affect the spinal intervertebral discs. Although several studies have been conducted to evaluate the effects of physical factors on disc health, little research has focused on the effect of prolonged stooped work on disc hydration- a critical component of disc health. The purpose of this study is to explore the connection between stooped work and low back pain through controlled mechanical loading and quantitative analysis of disc hydration during in vitro simulated stooped and erect loading conditions of porcine discs. The results showed that stooped postures exhibit significantly decreased overall water content relative to erect postures. Since as disc hydration forms the foundation for overall disc health and proper function, these results have implications for the injury mechanisms associated with stooped work. PMID- 22317074 TI - Principle component analysis of exposure variation analysis during computer work at presence of delayed onset muscle soreness. AB - Eleven healthy volunteers took part in three sessions where computer work was performed for 10 min in each session. The recordings were made on two consecutive days. After the first session, the subjects underwent a series of high intensity eccentric exercises of shoulder elevation to induce muscle soreness. The second session was performed immediately after the exercises and third session 24 hours after the exercise. Surface electromyography (EMG) of descending and ascending trapezius, deltoideus anterior and serratus anterior was recorded. Exposure variation analysis (EVA) centroid and marginal distribution was computed. Principle component analysis (PCA) was performed on both cases. Describing more than 80% of variance, first eight components for EVA marginal distributions and first four ones for EVA centroid were picked to be investigated. The sole EVA amplitude levels played a practically significant role to describe the variation in EVA marginal distribution. However, a significant pattern of load redistribution to superficial muscles was not found. This may suggest investigating the role of deep muscles in redistribution of load during computer work in response to high level eccentric contractions. PMID- 22317075 TI - Interactions between task repetition and psychosocial factors. AB - Psychosocial factors, individual factors, workplace requirements, and workplace organizational factors have all been reported as being associated with the risk of musculoskeletal disorders [11]. Huang, Feuerstein, and Sauter [5] described the various concepts and models proposed to link occupational stress and work related upper extremity disorders, as well as the difficulty in verifying the suggested linkages. Huang et al. [5] suggested that decomposing a complex model would be an appropriate method to begin the investigations of the proposed models. Task repetition is a workplace requirement that is considered a potential risk factor for cumulative trauma and its relationship to psychosocial factors was investigated. The study found only weak to no statistically significant relationship between task repetition and reported psychosocial factors of job stress in workers in Taiwan. PMID- 22317076 TI - Mitigation of musculoskeletal problems and body discomfort of agricultural workers through educational intervention. AB - Farming is a physically arduous occupation that places farm workers' at potential risk of musculoskeletal disorders, which has been observed to impose a greater impact on their health. Each activity in agriculture brings about certain stress and strain on bones and muscles leading to work-related musculoskeletal disorders which can lead to several permanent diseases and disabilities. The purpose of analyzing musculoskeletal problems among male and female workers engaged in agriculture was to know about the risk factors dangerous to health so that interventions can be planned for mitigating them thereby increasing the efficiency of work. Educational intervention included audio-visual aids as well as printed literature. It was hoped that awareness of these factors through dissemination of information would contribute at preventing hazards amongst farmers and their families. The results revealed that the workers reported very severe to severe pain in low back while performing agricultural activities. Weeding was the most strenuous activity for females and threshing crop for males. Training and education on MSDs through educational intervention proved that the knowledge of the farm workers could be enhanced and can help reduce risk of many musculoskeletal problems. It can be help in empowering the community and mitigate MSDs in agriculture. PMID- 22317077 TI - Swabbing: touchscreen-based input technique for people with hand tremor. AB - Interacting with touchscreen computer systems is a challenging task for elderly tremor patients, because of a lower input accuracy caused by their tremor symptoms. Previous observations by Mertens et al. suggested that continuous movements are able to lower these symptoms. In this paper Swabbing, a input method for touchscreen systems based on such motions, is presented. A user study will show that Swabbing is able to reduce the error rate while proving equal user satisfaction compared to standard input techniques. Furthermore reasons for these benefits will be argued and explained with the use of accuracy measures by MacKenzie et al. In the end possible future enhancements of Swabbing will be discussed. PMID- 22317078 TI - Evaluation of the exercise intervention with the "Back School" education program in a Brazilian company of cigars: a case study. AB - The purpose of this study was to assess the benefits of an exercise program associated to the educational phase of the "Back School Program" in the quality of life of workers from a cigar factory. This is a case study conducted over four months with three activities a week, two times a day, with the third day devoted to educational activities, focusing on healthy lifestyle, correct posture, postural orientations, daily living and work activities, work motivation, and other issues. PMID- 22317079 TI - Low back pain disability and stay at work: contradiction or necessity? AB - The incidence of occupational diseases in the population is high and factors such as long working hours, poor posture, psychological and physical stress can contribute to its development. Among work-related musculoskeletal disorders, back pain has a high prevalence. The aim of the present study was to quantify and characterize pain complaints and to identify individuals with low back pain, in order to assess the degree of disability. Participated 226 employees of an institution of higher education. They answered a general questionnaire about location and quantification of pain complaints visual analog scale for pain and the Quebec Disability Questionnaire. Of all the workers, 69.60% had some type of musculoskeletal complaint; of those, 15.41% had low back pain. Considering workers who had back pain, 54.9% were female, 52.94% are under 30 years old and 43.14% between 1 and 5 years of work. As for the final score for the degree of disability, 41.17% had minimal disability and 37.25% moderate disability. The present study found large number of pain complaints and high prevalence of low back pain, resulting in individual's inability and difficulties in performing work activities. PMID- 22317080 TI - Body discomfort in poultry slaughterhouse workers. AB - Brazil has the main producers and exporters of chicken meat, which is classified as the third largest world chicken meat producer and lead exporter. This study aimed at analyzing the body discomfort perception in poultry slaughterhouse workers and its associations with the task characteristics. The study included 290 workers, 200 women (34.7 +/- 7.7 years) and 90 men (36.8 +/- 8.2 years). A body map for evaluating discomfort and an interview regarding organizational issues and criteria of the OCRA method were used. Descriptive statistics and chi square test (p <= 0.05) were used. It was found that 87.6% of respondents performed repetitive tasks, 86.2% performed rest breaks, 82.8% performed job rotation (2-7 tasks) and 61% used tools. It was also found that 67.2% felt discomfort in at least one body region, and the symptoms most often reported were pain, fatigue and tingling. The body regions most frequently cited were: shoulders (62.6%), neck (46.2%), spine (36.4%), forearms (31.3%), arms (29.2%), wrists (25.6%) and hands (25.6%). In sectors artificially cold (n = 204), 54.1% felt cold. There was no association between body discomfort and gender, task characteristics, performance of rest breaks and job rotation, use of tools and time working in the company; however, there was association with cold perception (p = 0.035). PMID- 22317081 TI - Effect of low back pain on social and professional life of drivers of Kolkata. AB - Abstract Occupational driving has often been associated with a high prevalence of back pain. Buses constitute the backbone of the local transportation; so many people are engaged in the profession. The present study was to investigate the prevalence of low back pain (LBP) and due to that problem whether their social and professional life hampers or not. The present study was undertaken among 160 government undertaking male bus drivers. Modified Nordic musculoskeletal questionnaire was performed with physical assessment. Then Oswestry Low Back Pain Disability Questionnaire (QLBPDQ) was performed to evaluate the extent to which social and professional life is restricted by back pain. Afterwards, the sit-and reach test and investigation of sitting postures was done. From the analysis of questionnaire it was revealed that drivers had to spend 8-10 hours daily for 6 days in a shift. It was further observed that all of them mainly suffering from LBP. From the QLBPDQ analysis it was found that LBP restricted their social and professional life. Sit and reach test and posture analysis also support this finding. This result is an absolute reflection of the alarming situations of the Kolkata bus drivers. It can be concluded that the bus drivers are highly stressed due to the hazardous working conditions, which in turn may additionally affects their health and overall work performance in the long run. PMID- 22317082 TI - Computer use and ulnar neuropathy: results from a case-referent study. AB - We aimed to evaluate associations between vocational computer use and 1) ulnar neuropathy, and 2) ulnar neuropathy- like symptoms as distinguished by electroneurography. We identified all patients aged 18-65 years, examined at the Department of Neurophysiology on suspicion of ulnar neuropathy, 2001-2007. We mailed a questionnaire to 546 patients with ulnar neuropathy, 633 patients with ulnar neuropathy-like symptoms, and three community referents per case, matched on sex, age, and primary care centre. From a Job Exposure Matrix we extracted estimates of daily hours of computer use. The analysis was performed by conditional logistic regression.There were a negative association between daily hours of computer use and the two outcomes of interest. Participants who reported their elbow to be in contact with their working table for 2 hours or more during the workday had an elevated risk for ulnar neuropathy (OR=2.16, 95 % CI; 1.06 4.44).The two outcomes were not associated with daily hours of computer use. Findings suggested specific effects of pressure on the elbow, and might be an explanation for the overweight of left-sided outcomes in this primarily right handed group. Preventive efforts would then be straightforward by providing appropriate arm support for the left arm and elbow. PMID- 22317083 TI - Associations between psychosocial risk factors and musculoskeletal disorders: application to the IT profession in India. AB - The exponential growth of the information technology (IT) industry in India has been accompanied with a substantial increase in the reporting of work-related musculoskeletal disorders (WMSDs). The purpose of the current study was to identify and assess the contributions of prevalent psychosocial factors on perceived WMSD outcomes among IT professionals from India. About 77 IT professionals from India completed a survey set consisting of 26 question items from the Job Content Questionnaire and 3 separate question items pertaining to WMSD outcomes (pain/discomfort and psychological stress scores). The findings suggest prevalence of existing pain (shoulder/neck and low back) in more than one fourth of the respondents. Additionally two-thirds of the respondents had never had any ergonomics awareness training. Co-worker support and psychological work demands were found to be the strongest contributors of psychosocial risk factors towards pain/discomfort and psychological stress outcomes. Findings from this study highlight the influence of certain psychosocial traits of the Indian IT workplace on perceived WMSD outcomes. There is a need to develop and implement intervention strategies to address these factors that may help lower the risk of work-related musculoskeletal pain. PMID- 22317084 TI - Musculoskeletal symptoms, postural disorders and occupational risk factors: correlation analysis. AB - Work-related musculoskeletal disorders (WRMSD) include a list of inflammatory and degenerative diseases characterized by the presence of musculoskeletal symptoms, compensatory posture changes and functional disabilities. The objective of this study was to evaluate the kinetic/functional characteristics of textile plant workers, their level of exposure to risk factors and the contribution these make to musculoskeletal symptoms. The sample of 42 workers answered the Nordic Questionnaire and the Job Factors Questionnaire. The kinetic/functional characteristics of each worker were verified by a blinded evaluator. Data were analyzed using descriptive statistics and Pearson's correlation. Musculoskeletal symptoms were more prevalent in the spinal region and upper limbs. The exposure levels to risk factors were identified as a serious problem. Postural disorders, musculoskeletal symptoms and risk factors were correlated (P <= 0.05). PMID- 22317085 TI - Nurses' working tasks and MSDs back symptoms: results from a national survey. AB - Healthcare workers, namely registered nurses (RN), are frequently exposed to work related musculoskeletal disorders (WRMSDs) risk factors. Identifying the symptoms of these disorders is one of the first epidemiological steps to managing them. This study aims to identify WRMSDs prevalence symptoms in Portuguese RN. During 8 months (2010-2011) the National Public Health School and the Portuguese Registered Nurses Board made a call to all RN to answer an online WRMSDs questionnaire. Respondents (n=2140) are mostly females (77.4%) and work mainly in hospitals (n=1396) and in primary healthcare centers (n=421). Results show high symptoms prevalence (last 12 months) in the lower back (60.6%), the upper back (44.5%), and the neck (48.6%). Nurses' activity, especially patient hygiene in bed, is a strong contributor (p>0.05) to pain in the upper back (OR=1.39 [1.09 1.80]) and lower back (OR=1.4 [1.08-1.84]). Patient holdup without mechanical support has the highest relationship (p>0.05) between work tasks and symptoms in the last 12 months in the upper back (OR=1.50 [1.19-1.90]). Prevalence rates of WRMSDs symptoms in Portuguese nurses are no different from other studies with Swedish, Italian and Greek nurses. Maybe changes in healthcare systems didn't change the way care is delivered and we must rethink how to prevent nurses WRMSDs. PMID- 22317086 TI - Prevalence of musculoskeletal disorders among staffs in specialized healthcare centre. AB - This study was conducted to investigate pervasiveness of the musculoskeletal disorder (MSD) among staffs in a specialized healthcare centre. Sixty-eight staffs from three departments namely Cardiovascular Lab (CVL), Nuclear Radiology, and General Radiography were recruited in this study. A modified Nordic Musculoskeletal Questionnaire (NMQ) was distributed among study population. The result shows that the prevalence of MSD was highest in lower back (88.2%), neck (76.5%) and shoulder (60.3%) for the past 12 months followed by lower back and elbow (44.1%), and wrist (39.1%) correspondingly, for the past 7 days. Present results suggest that healthcare professionals - radiographers, patient assistants and nurses incurs MSD risks through work tasks as well as psychosocial factors. These include awkward posture during patient handling, workload, work stress and time pressure. Therefore, an ergonomics improvement on the job design and workspace are needed in order to reduce the MSD risks. PMID- 22317087 TI - Physical and psychosocial indicators among office workers from public sector with and without musculoskeletal symptoms. AB - Work-related musculoskeletal disorders (WRMD) are the result of the combination of different risk factors. They are very common among computer workers, mainly when neck and upper limbs are considered. Forty-two office workers from a public university participated in this study. They were divided into two groups: Symptomatic Subjects (SS, n=20) and Asymptomatic Subjects (AS, n=22), according to the Nordic Musculoskeletal Questionnaire (NMQ). Psychosocial indicators were assessed using the Job Content Questionnaire (JCQ) and Utrecht Work Engagement Scale (UWES). Workplaces were evaluated according to the Ergonomic Workplace Analysis (EWA), proposed by the Finnish Institute of Occupational Health. The NMQ showed higher weekly prevalence of complaints on neck, shoulders and wrist/hands (p=0.00) among SS. The annual prevalence of symptoms on wrist/hands was also higher among SS (p=0.02). The JCQ did not show any difference between groups (p>0.05). Higher proportion of servers with 'high level' of engagement, dedication and absorption, according to UWES, was identified among SS (p<0.01). EWA showed worse scores for 'Work Site', 'Job Content' and 'Repetitiveness of the Work' among SS (p<0.05). Servers are exposed to physical and psychosocial risk factors that can contribute to the development of WRMD. Work conditions need to be change in order to improve musculoskeletal health. PMID- 22317088 TI - An ergonomic study on the onset of mental fatigue among the load handling workers of a central market area in Kolkata. AB - It is a well recognized fact that manual material handling (MMH) entails enormous physical labor and associated discomfort feeling, which invariably culminate into musculoskeletal disorders. However mental fatigue, in such instances, becomes an unexplored parameter that needs definite attention during assessment of work status of MMH workers. The present study is being performed among 75 porters of a central market in Kolkata to ascertain the extent of physical and mental exhaustion among them. SF-12 health status questionnaire followed by another questionnaire involving psychosocial questions were performed among them. The analysis of both the questionnaires clearly revealed that most of the porters are under severe physical exertion as they alone carry about 120 kg load at a time and such activity is repeated at least 40 times throughout the day. They always suffer from pain and discomfort feeling at different body parts and this interferes with their normal work activity to a great extent. Moreover absenteeism means no financial return and even a day's rigourous work fetches meagre income. The inability to support family convincingly even after performing such hazardous tasks makes them feel low. Monotony, boredom, fatigue and mental trauma form an integral part of their daily work schedule. PMID- 22317089 TI - Discrepancies in pain presentation caused by adverse psychosocial conditions as compared to pain due to high physical workload? AB - Disorders in the musculoskeletal system have been associated with a high physical workload as well as psychosocial and individual factors. It is however not obvious which of these factors that is most important to prevent. Musculoskeletal disorders in neck and upper extremity was assessed by interview and clinical examination in 79 teachers and 93 assisting nurses, all females. Psychosocial work environment was assessed by questionnaire. The physical workload was recorded by technical measurements of postures, movements and muscular load, in 9 teachers and 12 nurses. The physical workload was lower among the teachers, but they had a more demanding psychosocial work environment. Among the nurses, but not in the teachers, the neck-shoulder disorders were associated with a high body mass index (BMI). The teachers reported neck-shoulder complaints to a higher extent than the nurses, but had much lower prevalence of diagnoses in the clinical examination (12% vs. 25%; POR 0.3 CI 0.1 - 1.2; adjusted for age and BMI). The results suggest that adverse psychosocial conditions among the teachers give rise to a different kind of pain in the neck-shoulder region than from physical overload, troublesome but not as severe as the one afflicting the nurses. PMID- 22317090 TI - Reducing whole body vibration in forklift drivers. AB - Forklift drivers in warehouses are often exposed to whole body vibration (WBV) during the total day. There is however an association between working as a forklift operator and the development of low back pain. In this study the exposure to WBV was measured in five forklift drivers who performed a standardised order picking task during 10 minutes. The effect of driving surface (uneven concrete vs. new flat concrete), driving speed (15 km/h vs. 8 km/h) and seat suspension (mechanical suspension vs. air suspension) was investigated. Improving the driving surface was the most effective preventive measure by reducing the whole body vibration with 39%, from 1.14 to 0.69 m/s2. Lowering the speed limit resulted in a reduction of WBV with 26% (1.05 vs. 0.78 m/s2). An air suspension seat was 22% more effective compared to mechanical suspension (1.02 vs. 0.80 m/s2). On uneven concrete an air suspension seat performed even better by reducing the WBV by 29% (1.33 vs. 0.95 m/s2). A combination of a new driving surface, limiting the maximum speed and the introduction of an air suspension seat reduced the whole body vibrations below the action limit of 0.5 m/s2 as mentioned in the European directive. None of the interventions were effective enough on their own. PMID- 22317091 TI - Analysis of urban cleanness agents' workstation on the appearance of work related musculoskeletal disorders. AB - This study had as objective to evaluate the workstation of the responsible for the collection of urban garbage in relation to the factors associates with the appearance or aggravation of WMRD, as well as identifying signals and symptoms of these illnesses in the related professionals. For this, was developed a form with open and closed questions, that approached item relative to the identification of the searched, to the organization and execution of the work and to the signals and symptoms of WMRD, e that was applied in 44 agents in a company of collection of urban residues in a Brazilian metropolis. As the results can be evidenced that between the factors that the cleanness' agents are susceptible to the appearance of WMRD can detach the lack of orientation of these professionals as the positions adopted in the work, the lack of training and qualification, as well as the repetitivity of tasks and not use of individual protection equipment. However, yet with the existence of innumerable factors of risk, evidenced a small incidence of pain. PMID- 22317092 TI - Evaluation and redesign of manual material handling in a vaccine production centre's warehouse. AB - This study was conducted in a warehouse at a vaccine production centre where improvement to existing storage and working conditions were sought through the construction of a new refrigerated store section (2-8C degrees ). Warehousing tasks were videotaped and ergonomics analysis tools were used to assess the risk of developing MSDs. Specifically, these tools were the Rapid Entire Body Assessment (REBA) and the NIOSH equation. The current plant layout was sketched and analyzed to find possible targets for improvement trough the application of general work space design and ergonomics principles. Seven of the eight postures evaluated with REBA had a total score between 8 and 10, meaning a high risk, and only one was at a medium risk level. Nine of the eleven manual material handling tasks analyzed with the NIOSH equation had a Lifting Index between 1.14 and 1.80 and two had a recommended weight limit of 0 kg, indicating a need for job redesign. Solutions included the redesign of shelves, the design of a two-step stair and a trolley with adjustable height; also, changes in work methods were proposed by introducing a two-workers lifting strategy and job rotation, and, finally, a restructuring of plant layout was completed. PMID- 22317093 TI - Biomechanical analysis of loading/unloading a ladder on a truck. AB - Loading/unloading a ladder on vehicles are frequent tasks and involve overhead handling that may expose workers to risk factors of shoulder musculoskeletal disorders. The objective of the present study was to evaluate posture, forces required and perceived exertion when loading and unloading the ladder on a utility truck. Thirteen male overhead line workers from an electric utility in Brazil participated in this study. Shoulder elevation angle was measured using inclinometers. The required force to load/unload the ladder was measured by dynamometer. Subjective assessment of the perceived exertion was recorded to compare the exertion reported during the test conditions to the field conditions. The task of loading/unloading the ladder presented risks of shoulder musculoskeletal disorders (MSDs) to workers because it requires high levels of force (approximately 60% of the maximal force) combined with overhead posture of the shoulders (more than 100 degrees from the neutral posture). Age and height presented to interfere in biomechanical risks presented in load/unload task. There was no significant difference between the subjective exertion during the test conditions and handling the ladder in the field. Ergonomic intervention is recommended to reduce these risks for shoulder MSDs. PMID- 22317094 TI - Evaluation of lumbar overload in hotel maids. AB - BACKGROUND: Work-related musculoskeletal disorders are responsible for important amount of declining productivity among workers. Its economic impact is considered important because, in some aspects, such as sickness absence, it can cause increase in costs for employers. This paper aimed at identifying whether the activities that the hotel maids perform during working hours may lead to the development of musculoskeletal disorders. METHODS: Cross-sectional study conducted in a hotel in the city of Sao Paulo, Brazil. Performed an ergonomic analysis of the job application with a checklist consisting of risk assessment of low back pain. RESULTS: The maids are responsible for the cleaning of hotel rooms, including to lean in order to clean the bathroom. The activity is associated with ergonomic risk for poor posture, manual transport of loads and use of physical force in the upper limbs. This job presents a moderate risk of low back pain according to checklist for assessing the ergonomic situation. CONCLUSIONS: Negative ergonomic aspects are associated with the development or aggravation of musculoskeletal disorders in these workers. We suggest modification in work organisation. Another possibility is decreased the weight of the carts, keeping areas of replacement material on each floor. PMID- 22317095 TI - Participatory ergonomics among female cashiers from a department store. AB - The objective of this paper was to control ergonomic risks among female cashiers working in a department store belonging to the retail market. This study was conducted between May and November 2010. Participatory ergonomics was applied through knowing and understanding how the company works, establishing the work team (Ergo group), training the team in ergonomics-related topics, and making decisions and interventions. The sample was composed of 71 participants--mostly female cashiers--, and all of them have a musculoskeletal compromise, declaring pain or discomfort mainly in the neck, lower back, right wrist and shoulders. Among others, following problems were found: postural overload, repetitive work, manual load handling, mental fatigue, environmental discomfort, variable work schedules, extended working days, and absence of breaks. In the intervention, the main implemented changes were the redesign of workstation, complete change of chairs and keyboards, and the implementation of a rotation system, as well breaks for compensatory exercises. After that, an evident improvement of found problems was observed, therefore it can be concluded that participatory ergonomics is an attractive methodology, appropriate and efficient for solving and controlling ergonomic risks and problems. PMID- 22317096 TI - Biomechanical strain of goldsmiths. AB - The work of the goldsmiths consists in the manufacture of jewelry. The piece, be it an earring, bracelet or necklace, is hand-assembled. This task requires precision, skill, kindness and patience. In this work, we make use of tools such as cuticle clippers and rounded tip, beads or precious stones and also pieces of metal. This type of activity requires a biomechanical stress of hands and wrists. In order to quantify the biomechanical stress, we performed a case study to measure the movements performed by an assembly of pieces of jewelry. As method for research, filming was done during assembly of parts to a paste, using a Nikon digital camera, for 1 (one) hour. The film was edited by Kinovea software, and the task was divided into cycles, each cycle corresponds to a complete object. In one cycle, there are four two movements of supination and pronation movements of the forearm. The cycle lasts approximately sixteen seconds, totaling 1800 cycles in eight hours. Despite the effort required of the wrists, the activity shows no complaints from the employees, but this fact does not mischaracterizes the ability of employees to acquire repetitive strain injuries and work-related musculoskeletal disorders. PMID- 22317097 TI - Risk factors for repetitive strain injuries among school teachers in Thailand. AB - Prolonged posture, static works and repetition are previously reported as the cause of repetitive strain injuries (RSIs) among workers including teachers. This cross-sectional analytic study aimed to investigate the prevalence and risk factors of RSIs among school teachers. Participants were 452 full-time school teachers in Thailand. Data were collected by the structural questionnaires, illuminance measurements and the physical fitness tests. Descriptive statistics and inferential statistics which were Chi-square test and multiple logistic regression analysis were used. Most teachers in this study were females (57.3%), the mean years of work experience was 22.6 +/- 10.4 years. The six-month prevalence of RSIs was 73.7%. The univariate analysis identified the related risk factors to RSIs which were chronic disease (OR=1.8; 95% CI = 1.16-2.73), history of trauma (OR=2.0; 95% CI = 1.02-4.01), member of family had RSIs (OR=2.0; 95% CI = 1.02- 4.01), stretch to write on board (OR=1.7; 95% CI = 1.06-1.70) and high heel shoe >2 inch (OR=1.6; 95% CI = 1.03-2.51). Multiple logistic regression analysis showed that chronic diseases and high heel shoe >2 inch significantly related to developing of RSIs. The poor grip strength and back muscle flexibility significantly affected RSIs of teachers. In conclusions, RSIs were highly prevalent in school teachers that they should be aware of health promotion to prevent RSIs. PMID- 22317098 TI - Job factors related to musculoskeletal symptoms among nursing personnel--a review. AB - The study aimed to conduct a literature review as a step of the development of a new questionnaire about the nursing workers' perception of job factors that may lead to musculoskeletal symptoms. An information synthesis was achieved by collecting data from studies that fitted the search criteria. The results showed that despite the existence of several job factors related to musculoskeletal symptoms, no specific questionnaire that evaluates this relationship was found. Therefore, this literature review presents important topics for developing the first questionnaire to analyze work activities that may contribute to pain and discomfort among nursing personnel. PMID- 22317099 TI - Study on lumbar kinematics and the risk of low back disorder in female university students by using shoes of different heel heights. AB - The study was taken up to investigate the effects of heel heights on lumbar kinematics and the risk of Low Back Disorder (LBD) in females. Nineteen female university students (24.5 +/- 3.36 yrs) volunteered in the study. Lumbar kinematics was measured by using Industrial Lumbar Motion Monitor (iLMM). The volunteers were asked to walk for a distance of 50 meters in 3 different given conditions i.e bare foot (Heel 0), with flat heels (Heel 1) and with high heels (Heel 2). Heights of Heel 1 and Heel 2 were 1.5 +/- 0.84 cm and 5.5 +/- 1.70 cm respectively. The Lumbar kinematic parameters studied were- Average Twisting Velocity (ATV), Maximum Sagital Flexion (MSF) and Maximum Lateral Velocity (MLV). It was observed that all the above mentioned Lumbar kinematics - ATV, MSF and MLV increases with increase of heel heights, which in turn increases the risk of LBD. As a result of increase in Lumbar kinematic values with increase in heel heights, LBD risk has also increased. Mean and SD of the LBD risk with Heel 0, Heel 1 and Heel 2 were 16.79 +/- 6.04%, 19.00 +/- 7.38% and 22.11 +/- 6.98% respectively. Lower stature with high heels showed higher risk of LBD than the higher stature with high heels. PMID- 22317100 TI - Motor variability--an important issue in occupational life. AB - Several recent reviews have reported that 'repetitive movements' is a risk factor for occupational musculoskeletal disorders (MSD) in the neck, shoulder and arm regions. More variation in biomechanical exposure is often suggested as an effective intervention in such settings. While increasing variation using extrinsic methods like job rotation may not always be possible in an industrial context, the intrinsic variability of the motor system may offer an alternative opportunity to increase variation. Motor variability (MV) refers to the natural variation in postures, movements and muscle activity observed to different extents in all tasks. The current review explores the state of the art in MV research from motor control, sports and occupational biomechanics literature to answer whether MV is important to consider in an occupational context, and if yes, whether this literature stimulates further studies to test if MV can be manipulated as a deliberate intervention for increasing biomechanical variation without jeopardizing production. PMID- 22317101 TI - Long periods with uninterrupted muscle activity related to neck and shoulder pain. AB - The aim was to analyze the relationship between periods with uninterrupted neck muscle activity for >= 4 min and neck and shoulder pain. The trapezius muscle activity was recorded bilaterally on 40 young workers and students during a full shift. Neck and shoulder pain, mechanical work load and decision control were reported at the same time as the muscle activity recording and 6 months later. A dose-response relationship was found between uninterrupted muscle activity and neck and shoulder pain, with a ten-fold higher risk for the group with more than half, compared to less than a third, of the shift with uninterrupted muscle activity. Self-reported mechanical work load showed a small but protective effect related to pain. Gender and decision control did not emerge as important risk factors in this model. In conclusion, this study indicates that work or other exposures that contains long periods with uninterrupted neck muscle activity of 4 min duration or longer should be minimized to reduce risk of neck and shoulder pain. PMID- 22317102 TI - Specificity of back muscle response to submaximal fatiguing contractions. AB - A fatigue-related decrease in quality and accuracy of the proprioceptive feedback from muscle spindles in the back (e.g. stretch reflexes) may lead to a deterioration of spinal stability, thereby making the spine more vulnerable to external perturbations. Endurance time, tissue oxygenation, reflex latency and blood pressure response were studied in twenty subjects during a submaximal endurance test of the back extensors (20 % MVC) performed as either a position task (supporting a weight stack while maintaining trunk position) or a force task (exerting a force against a dynamometer). Mean endurance time was 8.91 (+/- 2.79) min for the force task and 10.86 (+/- 6.93) min for the position task. This result is in striking contrast to what has previously been reported from limb muscles, and suggests that back muscles are especially well suited for postural tasks. An increased reflex latency found after the position task indicates that the disadvantage of the prolonged endurance time is a deterioration of the afferent input from the muscle spindles that may potentially hamper the protection of the spine. PMID- 22317103 TI - Stationarity test of electromyographic signals during isokinetic trunk exertions. AB - The aim of this study is to investigate the stationarity of the electromyographic (EMG) signals during isokinetic exertions of the trunk muscle. Six healthy subjects participated in this study. The erector spinae muscles were used to collect the signals. In order to simulate the isokinetic exercises of the trunk, a Cybex system with a trunk modular component was used. All subjects performed sustained exertions with a combination of load (25%, 50% MVC) and angular velocity (0, 15, 30 degree/s). The stationarity of the signals was tested by the reverse arrangements test and modified reverse arrangements test. In the results, the signal stationarity was high in all conditions in the reverse arrangements test. However, in the modified reverse arrangements test it was relatively low at about the 30 degree/s angular velocity. In the analysis of variance, the effect of angular velocity was statistically significant at the 0.05 significance level in the modified reverse arrangements test and Tukey's HSD grouping showed that the stationarity of 30 degree/s angular velocity was significantly different from 0, 15 degree/s condition. These results indicate that the stationarity of the EMG signals showed no difference between isometric and isokinetic conditions when the angular velocity was equal to 15 degree/s. PMID- 22317104 TI - Muscular activity in different locomotion plans with the use of various shoes types and barefoot. AB - The objective of this study was to evaluate the electromyographic activity of the muscles of the leg and spine associated with different types of shoes and barefoot, in the various plans of locomotion, in the situations before and after fatigue. METHODS: Is a cross-sectional study, which was used a sample of convenience with 15 young women, aged between 18 and 35 years, sedentary. The examined muscles were tibialis anterior, gastrocnemius medialis and lateralis and erector spinae. The muscular activity was assessed during locomotion on flat surface, up and down stairs and in an inclined surface. The shoes were a high heeled, small heeled, tennis, slipper and barefoot. RESULTS: The results of electromyographic analysis showed that the muscles of the leg had greater electromyographic activity in the position of pre-fatigue of the lower limbs and erector spinae in the postfatigue of the lower limbs, in most of the conditions and situations. DISCUSSION: Adaptive conditions associated with regular use of high shoes, has been widely questioned in relation to the incidence of injuries. CONCLUSION: In post-fatigue of the lower limbs, there was a decline in the activities of the muscles of the leg and increased recruitment of the erector muscles justified by the need for greater stability of the spine and pelvis during the locomotion of young women. PMID- 22317105 TI - Preventing Rsi/Wruld: use of esthesiometry to assess hand tactile sensitivity of slaughterhouse workers. AB - This research was conducted with slaughterhouse female workers in the municipality of Sao Miguel do Iguacu, state of Parana, Brazil. The sample was composed of 103 women aged 25 to 40 ( 7.57 years, and the study aimed to verify the nerve conduction of the median nerve. An esthesiometer consisting of a Semmes Weinstein monofilaments was used to measure the hand skin sensitivity in the region of the median nerve and a Jamar(r) hand dynamometer, which was used to determine the handgrip strength. About 81% of individuals had normal sensitivity with 0.05 g and average levels of handgrip strength in dominant hand (DH) of 35.30 kgf (( 3.10) and in the non-dominant hand (NDH) of 28.30 ( 3.09 kgf. 14% of individuals had reduced sensitivity, with values equivalent to 0.2 g and 2.0 g (blue and violet) and levels of handgrip strength in the DH equal to 28.10 kgf (( 2.90) and in the NDH of 26.40 kgf (( 3.28). 5% of individuals showed bilateral sensitivity deficit (4.0 g) and levels of handgrip strength in the DH of 16.10 kgf (( 2.10) and in the NDH of 18.20 kgf (( 3.28), resulting in a strong correlation between handgrip strength and sensitivity of the median nerve (r = 0.786) between variables dominant hand (DH) and (r = 0.626) for the non-dominant hand (NDH). It could be concluded that assessing the nerve conduction of the median nerve by hand esthesiometry can be an important tool in preventing the Carpal Tunnel Syndrome. PMID- 22317106 TI - Comparative analysis of assessment of the craniocervical equilibrium through two methods: cephalometry of Rocabado and cervical range of motion. AB - There are several instruments of evaluation of the craniocervical equilibrium; the most reliable are the radiographies. This study used the cephalometric analysis of Rocabado to measure the sensibility and specificity of the Cervical Range of Motion (CROM), a goniometer designed to assess cervical movements in degrees, and measure the forward head position in centimeters. This instrument frequently used, has been tested as a reliable instrument to evaluate the cervical movements but not the forward head. The sample consisted of 30 volunteers, 18 females, 12 males, mean age of 24.63 years. All participants were evaluated with CROM and radiographies in the resting head position and in erect head position. The values considered by the cephalometry consisted in the angle made between the McGregor plane and the vertical line formed by the base of the odontoid process to its apex; the posterior space between C0-C1 and C1-C2 and the hyoid triangle. RESULTS: 30% of the subjects had forward head posture, according to de cephalometry of Rocabado (decreased space between C0-C1, C1-C2) and 43,3% according to CROM. 16,6% had decreased posterior-inferior angle, and 13% had the hyoid triangle facing up. ROC curve of identifying forward head posture yielded area under the curve of 0,778 (95% confidence interval 0,596-0,960). The sensibility of CROM was: 77%. The specificity 71%. CONCLUSION: This study suggests that CROM has a moderate sensibility and specificity, useful for clinic use, but not for research. PMID- 22317107 TI - Analysis of temperature on the surface of the wrist due to repetitive movements using sensory thermography. AB - This study examines changes in body temperature generated in the wrist area through sensory thermography technique because of highly repetitive movements, proving with this technique that there is a decreased ability to perform muscular work, and thereby assess possible pathologies of Cumulative Trauma Disorders (CTDs). METHODS: Two healthy right-handed individuals, who performed repetitive work, emulating an operation of the textile industry for three days, generated DTA in the area of the wrist. The evaluation time was of 3 hours 30 minutes in a controlled temperature between 20 and 25 degrees C, 20 minutes stabilization time at the beginning and end of the operation. RESULTS: The maximum temperatures reached were on the right wrist (RW) of 35. 078 degrees C over a period of 1 hour 41 minutes 52 seconds; and on the left wrist (LR), 34.663 degrees C over a period of 2 hours 42 minutes 51 seconds, detected discomfort in their right shoulder and wrist in the time range which identified the highest temperatures. It was shown that the data does not fit a normal distribution for RW and LW; the data fit the three- parameters Weibull distribution for WR and LW with a correlation coefficient between 0.93 to 0.99. PMID- 22317108 TI - Functional analysis of scapular position in assymptomatic professors. AB - The impaired performance of the muscles of the scapular region may result in injuries, fatigue, weakness and pain. The main objective of this research was to analyze the scapular positioning during the abduction of the shoulder movement in the frontal, scapular and sagittal plans. METHOD: This cross-sectional study comprised a convenience sample of 20 individuals. It was used the disability of the arm, shoulder and hand questionnaire (DASH Brazil), the digital inclinometer was used for measuring the scapular positioning. Having the purpose of regulating and ensuring the correct positioning of the upper limbs Assessed in the plans, it was developed the bulkhead which was used while the examination was performed. RESULTS: The population study was asymptomatic. No significant difference was found for the right shoulder during the concentric and eccentric contraction at all angles of scapular inclination on the three analyzed plans. Significant difference was found in the left shoulder during the concentric contraction in the scapular angle at 90 degrees and in the eccentric contraction at the scapular angles of 30 degrees , 60 degrees and 90 degrees of inclination in the frontal plan compared to men and women. Furthermore, it was found a decreasing left shoulder in the scapular angle during the eccentric contraction above 90 degrees in the scapular and sagittal plans when compared to men and women. CONCLUSION: we concluded that in the three plans studied, the scapula behaved differently various angles in the measured and yet it was influenced by the direction of motion. Moreover, it is possible to say that showed that this study there is a difference in the rotational behavior of the scapula relating to women and men due to the anthropometric existed differences between them. PMID- 22317109 TI - Shoes influence in women posture. AB - One of the most prevalent aspects is women with complaints of discomfort in the lumbar region for the use of high heeled shoe. Authors described that there may be a relation between attitude and the present discomfort, often associated with muscular fatigue and increase the forces of reaction soil during the use of such footwear. The purpose of this study was to evaluate possible changes postural associated with the use of different types of shoes and barefoot. Fifteen sedentary women were subjected to a static evaluation posture with the use of the software SAPO. Analysis of variance (ANOVA) repeated measures was used to investigate differences between the shoes in all variables postural analyzed. The results showed no significant difference in static position with the types of shoes and barefoot. It was concluded that the shoes did not interfere in static position. PMID- 22317110 TI - Can digital signals from the keyboard capture force exposures during typing? AB - An exposure-response relationship has been shown between muscle fatigue and its effects on keystroke durations. Since keystroke durations can readily be measured by software programs, the method has the potential as a non-invasive exposure assessment tool. However, the software based keystroke durations may be affected by keyswitch force-displacement characteristics. Thus, this study used a force platform to measure the keystroke durations and compared them to software measured keystroke durations in order to determine whether the software based keystroke durations can be used as a surrogate force exposure measures. A total of 13 subjects (6 males and 7 females) typed for 15 minutes each on three keyboards with different force-displacement characteristics. The results showed that the software based keystroke durations were more sensitive to the keyboard force-displacement differences than the force based measures. Although the digital signal based keystroke durations depend on the force-displacement characteristics, the high correlation between the two measures indicated that the keystroke durations derived from the digital signal approximated the true force derived keystroke durations, regardless of the keyboard force-displacement characteristics. Therefore, the software based keystroke durations could be used as a non-invasive, surrogate force exposure measure in lieu of the more invasive actual force measurements. PMID- 22317111 TI - Notebook computer use with different monitor tilt angle: effects on posture, muscle activity and discomfort of neck pain users. AB - This study aimed to evaluate the posture, muscle activities, and self reported discomforts of neck pain notebook computer users on three monitor tilt conditions: 100 degrees , 115 degrees , and 130 degrees . Six subjects were recruited in this study to completed typing tasks. Results showed subjects have a trend to show the forward head posture in the condition that monitor was set at 100 degrees , and the significant less neck and shoulder discomfort were noted in the condition that monitor was set at 130 degrees . These result suggested neck pain notebook user to set their monitor tilt angle at 130 degrees . PMID- 22317112 TI - Usability analysis of 2D graphics software for designing technical clothing. AB - With the advent of technology, the computer became a working tool increasingly present in companies. Its purpose is to increase production and reduce the inherent errors in manual production. The aim of this study was to analyze the usability of 2D graphics software in creating clothing designs by a professional during his work. The movements of the mouse, keyboard and graphical tools were monitored in real time by software Camtasia 7(r) installed on the user's computer. To register the use of mouse and keyboard we used auxiliary software called MouseMeter(r), which quantifies the number of times they pressed the right, middle and left mouse's buttons, the keyboard and also the distance traveled in meters by the cursor on the screen. Data was collected in periods of 15 minutes, 1 hour and 8 hours, consecutively. The results showed that the job is considered repetitive and high demands physical efforts, which can lead to the appearance of repetitive strain injuries. Thus, the goal of minimizing operator efforts and thereby enhance the usability of the examined tool, becomes imperative to replace the mouse by a device called tablet, which also offers an electronic pen and a drawing platform for design development. PMID- 22317113 TI - The effects of new ways of work in the Netherlands: national data and a case study. AB - In 2010 15.2% of the work force in the Netherlands works with a computer at another location than at the office or at the clients' location. 27% of the Dutch working population is not satisfied about the possibility to work at home and 18% is not satisfied on the possibility to plan your own working time. The case control study affirms what has been reported as effects of new ways of work: the experienced productivity by communication and the representativeness of the office interior are improved and attention is needed for workers that need concentration space and need to personalize their work environment. In implementing new ways of work these issues need attention. PMID- 22317114 TI - New Ways of Working: does flexibility in time and location of work change work behavior and affect business outcomes? AB - In the changing modern economy some new factors have been addressed that are of importance for productivity and economic growth, such as human skills, workplace organization, information and communication technologies (ICT) and knowledge sharing. An increasing number of companies and organizations are implementing measures to better address these factors, often referred to as 'the New Ways of Working (NWW)'. This consists of a large variety of measures that enable flexibility in the time and location of work. Expectations of these measures are often high, such as a reduction in operating costs and an increase of productivity. However, scientific proof is still lacking, and it is worth asking whether al these implementations actually cause a change in work behavior and effect business outcomes positively. This article describes a case study of three departments (total of 73 employees) that changed from a traditional way of working towards a new way of working. Questionnaires and a new developed objective measurement system called 'work@task' were used to measure changes in work behavior (i.e. increased variation in work location, work times and a change towards NWW management style) and the effect on business objectives such as knowledge sharing, employees satisfaction, and collaboration. PMID- 22317115 TI - Examining the macroergonomics and safety factors among teleworkers: development of a conceptual model. AB - With the rising number of teleworkers who are working in non-traditional work locations, health and safety issues are even more critical. While telework offers attractive alternatives to traditional work locations, it is not without challenges for employers and workers. A macroergonomics approach or work system design for telework programs is proposed to address these new challenges. This approach explains the impact of organizational, psychosocial and workplace risk factors on teleworker's health and safety. A process for managing the health and safety of teleworkers is presented along with preventive strategies to provide an injury-free working environment. PMID- 22317116 TI - Expectation changes and team characteristics in a participatory design process. AB - A human factors specialist researched the expectations of a culturally and professionally diverse team throughout a year long participatory design process of a large processing facility. For a deeper understanding of high-level team expectations and characteristics, the specialist collected data and information through in-situ ethnography and traditional case study methods, personal interviews, and a questionnaire that included a likert scale rating for expectation levels. Results found that expectation levels rated extremely satisfied for individual team members and the overall team itself before and during the participatory process. In contrast, expectations for upper management from the team were satisfied before the participatory process, but changed to uncertain, to unsatisfied, to extremely unsatisfied during the process. Additionally, the participatory design team exhibited high-level team characteristics to include honesty, competence, commitment, communication, creativity, and clear expectations. PMID- 22317117 TI - Occupational health and safety professionals strategies to improve working environment and their self-assessed impact. AB - Research suggests that Occupational Health and Safety (OHS) practitioners have difficulty influencing the decision-making process because they are placed on the sidelines in the organisation. This paper analyses the strategies that OHS practitioners use to fulfill their job role and the impact they have on the working environment and OHS management systems. Semi-structured interviews were conducted with ten New Zealand OHS practitioners from mainly large private and public organisations about their job role, OHS tasks, strategies and their impact. The interviews were tape recorded, transcribed, entered into a qualitative data management programme and analysed thematically in relation to their strategies, barriers and their impact on the OHS management system and working environment. The analysis revealed that these OHS practitioners used multiple strategies - chosen in relation to the situation, the stakeholders and their own resources. They saw themselves as change agents or facilitators. They preferred to use a knowledge strategy, supported by an audit strategy. Their last resort was a regulation strategy. All of the practitioners had a positive impact on stakeholders' knowledge, attitude and behavior and on OHS management systems. Some practitioners improved the working environment but few were involved in introduction of new technology. PMID- 22317118 TI - Implementation of ergonomics in a service unit: challenges and advances. AB - This article discusses the implementation of ergonomics in a service unit of a major company in the energy sector. From the perspective of management, it analyses the process of implementation of ergonomics programmes in four operational areas. The objective was to diagnose the level of implementation of ergonomics. The study is descriptive, undertaken through the interaction with the technical staff of the operational areas involved, incorporating the perception of these role players concerning their work routines. The results indicated significant differences in the level of implementation of the programmes, especially those concerning structural conditions. Important conquests were registered, such as the investment in the training of specialists, the establishment of a facilitator network and the improvement of the standard for the directioning and alignment of the execution of initiatives. The linking in of the programmes with those of occupational health management emphasises its contribution to the safety and well-being of the workforce through interventions aimed mainly at eliminating and reducing ergonomic biomechanical risks. However, the need to broaden and deepen the ergonomic approach regarding organizational and cognitive aspects, as well as the insertion of ergonomics in project design of new work spaces and processes were also identified. PMID- 22317119 TI - Implantation of an ergonomics administration system in a company: report of an occupational therapist specialist in ergonomics. AB - This article aims to describe step-by-step the implementation of an ergonomics administration system in a company from March 2009 till March 2011 by an occupational therapist specialist in ergonomics based on the OSHAS 18001 guidelines and the Regulatory Norms 17 manual. The process began with the definition of five requisites with bases on the manual of application of the Regulatory Norms 17: survey; materials individual transportation and discharge; workplace furniture; workplace equipments; work environment and organization of the work to be managed with bases on the OSHAS 18001 guidelines. The following steps were established: sensitization of the company high administration, elaboration and institution of an ergonomics politics, development of ergonomics committees, ergonomics analysis of the work with recommendation of ergonomic improvements, implantation of improvements and evaluation or the results. This research experiment suggests the importance not only of a guiding axle but also of a professional qualification and participation of the company on the implementation of an ergonomics management system. PMID- 22317120 TI - The PhOCoe Model--ergonomic pattern mapping in participatory design processes. AB - The discipline and practice of human factors and ergonomics is quite rich in terms of the availability of analysis, development and evaluation tools and methods for its various processes. However, we lack effective instruments to either map or regulate comprehensively and effectively, cognitive and organizational related impacts, especially the environmental ones. Moreover, when ergonomic transformations through design - such as a new workstation design or even an entire new facility - is at play, ergonomics professionals tend to stay at bay, relying solely on design professionals and engineers. There is vast empirical evidence showing that participation of ergonomists as project facilitators, may contribute to an effective professional synergy amongst the various stakeholders in a multidisciplinary venue. When that happens, everyone wins - users and designers alike -because eventual conflicts, raised up in the midst of options selection, are dissipated in exchange for more convergent design alternatives. This paper presents a method for participatory design, in which users are encouraged to actively participate in the whole design process by sharing their real work activities with the design team. The negotiated results inferred from the ergonomic action and translated into a new design, are then compiled into a "Ergonomic Pattern Manual". This handbook of ergonomics-oriented design guidelines contains essential guidelines to be consulted in recurrent design project situations in which similar patterns might be used. The main drive is simple: nobody knows better than workers themselves what an adequate workplace design solution (equipment, workstation, office layout) should be. PMID- 22317121 TI - Macroergonomic aspects in the design of development programs in IDCs. AB - This paper revisits three reports on ergonomic aspects of development initiatives taking place in Industrially Developing Countries (IDCs). These include a macro ergonomics intervention in a habitation community in Cape Verde (aimed at designing solutions contributing to sustainable development), the evolution of poultry growers' control strategies as an integrative broiler operation is introduced in Mozambique, and a set of macro-ergonomic considerations related to the Agro Forestry Village Project in Mozambique. The paper seeks to set the reviewed development endeavors against the backdrop of the goals of ergonomics interventions. This reflection may inform development agents in future processes of design and implementation of integrated community and work systems transformation. PMID- 22317122 TI - Conditions for the successful integration of Human and Organizational Factors (HOF) in the nuclear safety analysis. AB - This communication presents some elements which come from the experience feedback at CEA about the conditions for the successful integration of HOF in the nuclear safety analysis. To point out some of these conditions, one of the concepts proposed by Edgar Morin to describe the functioning of "complex" systems: the dialogical principle has been used. The idea is to look for some dialogical pairs. The elements of this kind of pair are both complementary and antagonist to one another. Three dialogical pairs are presented in this communication. The first two pairs are related to the organization of the HOF network and the last one is related to the methods which are used to analyse the working situations. The three pairs are: specialist - non-specialist actors of the network, centralized - distributed human resources in the network and microscopic - macroscopic levels of HOF methods to analyse the working situations. To continuously improve these three dialogical pairs, it is important to keep the differences which exist between the two elements of a pair and to find and maintain a balance between the two elements of the pairs. PMID- 22317123 TI - Analysis of organizational conditions for risk management: the case study of a petrochemical site. AB - This paper presents an ergonomic intervention in the petrochemical sector. The scheduled shutdown of one of the gas production sites has led the management to reduce the number of personnel on site, and then to get new recruits and experienced technicians from other sites as the policy for leaving personnel had not been properly planned, resulting in understaffing on site. Workers with seniority on the site, and who are also the most experienced do not accept the way newcomers are induced on site, whereas the management accuses them of resisting change. The intervention consisted in reconnecting local and corporate management through making the work activity visible and linking two sets of data that they held separately. Different types of analyses were made, work demography, decision making processes and tools used by the management, analysis of the building of career and work logics. Those different levels of analysis are gathered in macro-ergonomics, while showing the possible combinations between top down and bottom up approaches. The intervention resulted in concrete changes: HR simulation tool, training organisation, feedback. PMID- 22317124 TI - Organizational issues that impact on non-use of equipment for individual protection: a view of ergonomics. AB - The investigative focus of this paper is the issue of non-use of PPE (personal protective equipment) in a trading company of chilled and frozen food products. To conduct the study we have used an ergonomic work analysis that allowed us to highlight important organizational aspects that contribute to the non-use of such equipment. In conclusion, there are suggestions for minimizing problems. PMID- 22317125 TI - Analysis of the strain on employees in the retail sector considering work-life balance. AB - Many companies currently strive to support their employees' work-life balance through appropriate measures in order to improve employees' loyalty towards the company and to recruit new employees. In this context, flexibility in the area of working times is a measure that can influence employees' private lives immensely. This is why the individualisation of working time arrangements has been accorded high importance in current discussions on work-life balance. In this area, best practice examples can be found showing how working-time arrangements can improve the situation of the employees. It should be noted, however, that there is not one single perfect working-time model. A working-time model must always be adapted specifically to the actual situation of the company and the employees. Therefore, a targeted analysis of the challenges facing the company and the demands on the employees is essential for the creation of an appropriate working time policy. In particular, the employees' working-time preferences must be appropriately taken into account. Owing, however, to a combination of organisational complications and legal data protection restrictions, it is for the most part impossible to meet these working-time preferences in their entirety. This paper, which is based on an employee survey, illustrates the strain on employees in the retail sector and identifies different types of working-time preferences. PMID- 22317126 TI - Visualization of regulations to support design and quality control--a long-term study. AB - The aim of the study was to visualize design regulations of furniture by means of interactive technology based on earlier studies and practical examples. The usage of the visualized regulations was evaluated on two occasions: at the start when the first set of regulations was presented, and after six years of usage of all regulations. The visualized regulations were the result of a design process involving experts and potential users in collaboration with IKEA of Sweden AB. The evaluations by the different users showed a very positive response to using visualized regulations. The participative approach, combining expertise in specific regulations with visualization of guidelines, resulted in clear presentations of important regulations, and great attitudes among the users. These kinds of visualizations have proved to be applicable in a variety of product areas at IKEA, with a potential for further dissemination. It is likely that the approaches to design and visualized regulations in this case study could function in other branches. PMID- 22317127 TI - Macroergonomic analysis of two different work organizations in a same sector of a luminary manufacturer. AB - This article presents the analysis of the effect of two different types of work organization (the traditional and a new mechanized, more segmented one) in the packing sector of a luminary manufacturing company in Curitiba, Brazil. A macroergonomic analysis was conducted to evaluate the workers satisfaction with the job; the possible associated postural risk, the level of body pain/discomfort and to compare the two models (traditional and mechanized). The mechanized model showed to involve higher postural risk, to generate more pain and less satisfaction, even in relation to the temperature, illumination, uniform and salary, which are the same for the two groups. Excluding job rotation that was well evaluated and should be adopted for all workers, the new model proved to be worse than the traditional although it also needs improvements. PMID- 22317128 TI - Macroergomonics' contribution to the effectiveness of collaborative supply chains. AB - This article presents a conceptual model that combines Macroergonomics and Supply chain. The authors combine their expertise on these individual topics, building on their previous research. The argument of the paper is that human factors are key to achieve effective supplier-customer collaboration. A conceptual model is presented, its elements and their interactions are explained. The Content-Context Process is applied as a departing point to this model. Macroergonomics aspects considered are: a systemic approach, participatory ergonomics, formation of ergonomics teams and evaluation of ergonomics projects. The expected outcomes are: (a) improvement of production and productivity levels, (b) improvement of the product quality, (c) Reduction of absenteeism, (d) Improvement in the quality of work life (from the employees' perspective), and (e) increase in the employees' contribution rate of ideas for improvement. A case study was carried out at a vitroplant production organisation incorporating environmental aspects to obtain sustainable benefits. PMID- 22317129 TI - Understanding the collaborative-participatory design. AB - In this study, the role of collaboration in design is discussed, placing emphasis on how to include end-users in the development process. The study is based on a literature review focusing on aspects of collaboration in design, usability and human factors. Thereby, it introduces, compares and contrasts the characteristics of both collaborative and user-centered design perspectives, leading to the collaborative-participatory design approach. Finally, the advantages, disadvantages and precautions of implementing collaborative and participatory models are pointed out. PMID- 22317130 TI - Participatory design in lean production: which contribution from employees? For what end? AB - The proponents of lean production have pointed to the positive effects of the work organization on employees in terms of autonomy, enhanced skills and empowerment mainly by their participation into the continuous improvement of work process. But studies that have examined this issue suggest that the increase in autonomy is not sufficient to compensate for increases work intensity. Participatory design has grown extensively in manufacturing since the 1980's under the impulsion of the Scandinavian socio-technical system approach and it's central in the model of lean production performance. Its main objectives are to improve quality, increase productivity and safety through employee's participation to the reduction of non-value added activities, such as defined by lean production. In the line of the studies on participatory design and continuous improvement the present study examines the functioning of work groups, based on the kaizen model, the aim of which was to improve the proportion of "value-added activities" and working conditions, essentially physical constraints. The main results are consistent with the literature and show that accelerated forms of re-conception activities give employees limited room for maneuver to elaborate solutions based on the analysis of the real activity. This study is part of a broader initiative that goes in the direction of continuous improvement of the design process itself so that it integrates the real constraints of work and propose changes bases on work as it actually takes place, beyond pre-established performance goals bases on the reduction of "non added value activities". PMID- 22317131 TI - The workers role in knowledge management and sustainability policies. AB - Based on the concepts of sustainability and knowledge management, this article seeks to identify points of contact between the two themes through an exploratory study of existing literature. The first objective is to find, in international literature, the largest number of papers jointly related to the theme of knowledge management and sustainability. In these documents, the authors looked at the kind of relationship existing between the two themes and what the benefits introduced in organizations are. Based on an ergonomic point of view, the second objective of this article is to analyze the role of the worker (whether at the strategic or operational level) and his importance in this context. The results demonstrate that there is very little literature that addresses the two themes together. The few papers found, however, can be said to show the many advantages of introducing sustainability policies supported by adequate knowledge management. Very little has been studied with regards to the role of workers, which could be interpreted as meaning that little importance is given to the proactive role they may play. On the other hand, there is a high potential for future research in these areas, based on the high level of consideration of workers in knowledge management and sustainability literature, as well as in literature in the areas of ergonomics and sociology. PMID- 22317132 TI - Ergonomic sustainability based on the ergonomic maturity level measurement. AB - This paper aims at the application of an ergonomic maturity model (EMM), in order to assess the ergonomic sustainability outreach of ergonomic actions. This proposition was motivated by the widespread sensation that the development of the discipline, its educational devices and related practices depends on the attitude of ergonomics practitioners rather than environmental macroergonomic conditions. Maturity modeling in this paper is undertaken as a tool for ergonomic practitioners. Thus, its foundations were uprooted from diverse fields: Clinic Psychology, Quality Management and Project Management. The paper brings about a detailled explanation of this ergonomic maturity tool. The empirical part is fulfilled by the examination - using the EMM - of four emblematic cases excerpted from our research lab ergonomic portfolio. PMID- 22317133 TI - How could you use the ergonomics 'knowhow' transfer management to enhance human working for sustainable improvements in industrially developing countries? AB - This paper describes the different strategic understanding from getting ergonomics intervention programmes' conversations to 'Tip', including minimizing strategies; tipping point strategies; and maximizing strategies from building ergonomics intervention techniques. Those have indicated to different recognitions: 1) when amplification of the 'problem' is necessary; 2) when amplification of the 'tipping point' is necessary, and 3) when amplification of the 'success' is necessary. The practical applications and implications of the ergonomics intervention techniques are drawn from the findings of framing positive questions: 1) what is successful ergonomics intervention technique right now (Appreciative)? 2) What do we need to change for a better future (Imagine)? 3) How do we do this (Design)? 4) Who takes action and with what consequences (Act)? This requires re-framing of the ergonomics intervention techniques in an appreciative way, because of, the future action needs to be inspired by those things that participants feel are worth valuing, worth celebrating and sustaining. PMID- 22317134 TI - Sustainable development induction in organizations: a convergence analysis of ISO standards management tools' parameters. AB - Organizations are part of an environment in which they are pressured to meet society's demands and acting in a sustainable way. In an attempt to meet such demands, organizations make use of various management tools, among which, ISO standards are used. Although there are evidences of contributions provided by these standards, it is questionable whether its parameters converge for a possible induction for sustainable development in organizations. This work presents a theoretical study, designed on structuralism world view, descriptive and deductive method, which aims to analyze the convergence of management tools' parameters in ISO standards. In order to support the analysis, a generic framework for possible convergence was developed, based on systems approach, linking five ISO standards (ISO 9001, ISO 14001, OHSAS 18001, ISO 31000 and ISO 26000) with sustainable development and positioning them according to organization levels (strategic, tactical and operational). The structure was designed based on Brundtland report concept. The analysis was performed exploring the generic framework for possible convergence based on Nadler and Tushman model. The results found the standards can contribute to a possible sustainable development induction in organizations, as long as they meet certain minimum conditions related to its strategic alignment. PMID- 22317135 TI - Involvement and emancipation of the worker. Action research in a university hospital. AB - The present action research article is linked to an ergonomics project in a university hospital. The author's proposal is to focus action on the effective worker involvement required for the creation of spaces/mechanisms within organizations where people can enhance cooperation and deliberation on matters relating to work. For this purpose, a committee was introduced to assist in finding problems and solutions directly in work situations, so that workers could experience relative autonomy allowing them to develop procedures and choose tools appropriate to their own real needs. Based on this organizational implementation and on subsequent interviews, the practical results are analyzed and related to employee involvement. One can conclude that workers in all areas of the organization can be active elements for improving working conditions and productivity in companies. PMID- 22317136 TI - Partnering for workplace health and safety. AB - Worker involvement in decision-making about the workplace can improve safety, health, productivity and the quality of organizational outputs. Australian work health and safety (WHS) legislation mandates worker involvement and gives elected Health and Safety Representatives (HSRs) specific powers, but there has been limited research about the impact of that regulatory framework on the nature, quality and outcomes of worker involvement. As part of a wider review of worker representation in WHS, we investigated the role and impact (positive and negative) of elected HSRs on WHS] in South Australia using a newly-constructed survey instrument. This paper reports on the development of the instrument and the initial findings of the research. The initial survey dimensions and items were developed from earlier research on consultation in South Australia and were refined and validated through this research. The survey has 9 constructs and 61 items and has both face validity and high internal consistency. This research is a step forward for researchers and policy makers seeking a means of determining the effectiveness of worker participation in WHS. It provides an instrument, pilot baseline data and a method that could be used internationally to enable this assessment. PMID- 22317137 TI - Development of a knowledge management system for complex domains. AB - Deutsche Flugsicherung GmbH, the German Air Navigation Service Provider, follows a systematic approach, called HERA, for investigating incidents. The HERA analysis shows a distinctive occurrence of incidents in German air traffic control in which the visual perception of information plays a key role. The reasons can be partially traced back to workstation design, where basic ergonomic rules and principles are not sufficiently followed by the designers in some cases. In cooperation with the Institute of Ergonomics in Darmstadt the DFS investigated possible approaches that may support designers to implement ergonomic systems. None of the currently available tools were found to be able to meet the identified user requirements holistically. Therefore it was suggested to develop an enhanced software tool called Design Process Guide. The name Design Process Guide indicates that this tool exceeds the classic functions of currently available Knowledge Management Systems. It offers "design element" based access, shows processual and content related topics, and shows the implications of certain design decisions. Furthermore, it serves as documentation, detailing why a designer made to a decision under a particular set of conditions. PMID- 22317138 TI - Prevention of MSD within OHSMS/IMS: a systematic review of risk assessment strategies. AB - The purpose of this systematic review was to identify and summarize the research evidence on prevention of Musculoskeletal Disorders (MSD) within Occupational Health and Safety Management Systems (OHSMS) and Integrated Management Systems (IMS). Databases in business, management, engineering and health and safety were systematically searched and relevant publications were synthesized. The number of papers that could address the research questions was small. However, the review revealed that many of the techniques to address MSD hazards require substantial background knowledge and training. This may limit employees' involvement in the technical aspects of the risk assessment process. Also these techniques did not usually fit into techniques used by companies to address other risk factors within their management systems. This could result in MSD prevention becoming a separate issue that cannot be managed with company-wide tools. In addition, this review also suggested that there is a research gap concerning the MSD prevention within companies' management systems. PMID- 22317139 TI - Macroergonomic analysis of an assembly sector of a furniture company. AB - From of Macroergonomic Analysis of Work were diagnosed the main ergonomics demands in a furniture company in the city of Cambe, Parana. Through this method we could identify the most problematic points of the analyzed environment for posterior solutions of improvement with the objective of increasing the working and psychological quality of the employees, motivating their good performance and satisfaction. PMID- 22317140 TI - Linking human factors to corporate strategy with cognitive mapping techniques. AB - For human factors (HF) to avoid being considered of "side-car" status, it needs to be positioned within the organization in such a way that it affects business strategies and their implementation. Tools are needed to support this effort. This paper explores the feasibility of applying a technique from operational research called cognitive mapping to link HF to corporate strategy. Using a single case study, a cognitive map is drawn to reveal the complex relationships between human factors and achieving an organization's strategic goals. Analysis of the map for central concepts and reinforcing loops enhances understanding that can lead to discrete initiatives to facilitate integration of HF. It is recommended that this technique be used with senior managers to understand the organizations' strategic goals and enhance understanding of the potential for HF to contribute to the strategic goals. PMID- 22317141 TI - Economics of human performance and systems total ownership cost. AB - Financial costs of investing in people is associated with training, acquisition, recruiting, and resolving human errors have a significant impact on increased total ownership costs. These costs can also affect the exaggerate budgets and delayed schedules. The study of human performance economical assessment in the system acquisition process enhances the visibility of hidden cost drivers which support program management informed decisions. This paper presents the literature review of human total ownership cost (HTOC) and cost impacts on overall system performance. Economic value assessment models such as cost benefit analysis, risk cost tradeoff analysis, expected value of utility function analysis (EV), growth readiness matrix, multi-attribute utility technique, and multi-regressions model were introduced to reflect the HTOC and human performance-technology tradeoffs in terms of the dollar value. The human total ownership regression model introduces to address the influencing human performance cost component measurement. Results from this study will increase understanding of relevant cost drivers in the system acquisition process over the long term. PMID- 22317142 TI - Job stress management protocol using a merge between cognitive-behavioral techniques and ergonomic tools. AB - This paper presents a protocol for work distress assessment. Work distress is defined as a merge between nonergonomic related aspects, in tasks or environment, and adversely conditions perceived for a worker, in a certain work situation. This frame requires an approach that can treat individuals and organizational factors in the same way, at the same time. For this, we elaborate a psycho ergonomics method, associating concepts and practices from cognitive-behavioral techniques and work ergonomic analysis, which we named CEWAT - Cognitive Behavioral Work Analysis Technique. This paper presents CEWAT's foundations and structure, in steps. An application to a complex and dangerous system illustrates its benefits in the ergonomics action. PMID- 22317143 TI - Measuring organizational effectiveness in information and communication technology companies using item response theory. AB - The aim of this paper is to measure the effectiveness of the organizations Information and Communication Technology (ICT) from the point of view of the manager, using Item Response Theory (IRT). There is a need to verify the effectiveness of these organizations which are normally associated to complex, dynamic, and competitive environments. In academic literature, there is disagreement surrounding the concept of organizational effectiveness and its measurement. A construct was elaborated based on dimensions of effectiveness towards the construction of the items of the questionnaire which submitted to specialists for evaluation. It demonstrated itself to be viable in measuring organizational effectiveness of ICT companies under the point of view of a manager through using Two-Parameter Logistic Model (2PLM) of the IRT. This modeling permits us to evaluate the quality and property of each item placed within a single scale: items and respondents, which is not possible when using other similar tools. PMID- 22317144 TI - A computerized system to monitor resilience indicators in organizations. AB - The concepts developed by resilience engineering allow the understanding and monitoring the functioning of organizations and, particularly, to map the role of human activities, in success or in failure, enabling a better comprehension about how people make decisions in unexpected situations. The capture of information about human activities in the various organization levels gives managers a deeper real-time understanding of what is influencing the people performance, providing awareness of the factors that influence positively or negatively the organizational goals initially projected. The monitoring is important because the correct functioning of complex systems depends on the knowledge that people have to perform their activities and how the system environment provides tools that actually support the human performance. Therefore, organizations should look forward through precursors in operating signals to identify possible problems or solutions in the structure of tasks and activities, safety, quality, schedule, rework, and maintenance. We apply the concepts of resilience engineering to understand the organization by the analysis of cognitive tasks and activities. The aim is the development of a computerized system to monitor human activities to produce indicators to access system resilience. The validation of the approach was made in a real organization and the results show the successful applicability of the system. Based on findings obtained after the experiment of the system in a real organization, and managers and workers opinions, it was possible to show that the use of system provided an anticipated (real-time) perception about how activities are effectively being performed, allowing managers and workers to make decisions more consistent with daily problems, and also to anticipate solutions to cope with unexpected situations. PMID- 22317145 TI - A program to support the construction and evaluation of resilience indicators. AB - The main objective of this work is to propose a method and a tool to support the development of indicators able to inform an organization about the state of its resilience through a cyclical process of identifying its resilience factors, proposing resilience indicators, assessing its organizational resilience followed by assessing and improving the resilience indicators. The research uses concepts from complex adaptive systems and from resilience engineering to establish an initial set of indicators able to assess elements that contribute to organizational resilience, and structures them temporarily as a hierarchy. A software application to support indicator definition and structuring, questionnaire generation, and result assessment activities was built to assist in speeding up the experiment-adjust cycle. Prototype indicators were instantiated with helicopter operating companies in mind, and were reviewed by a domain expert. PMID- 22317146 TI - Organizational ergonomics of occupational health methods and processes in a Brazilian oil refinery. AB - Organizational ergonomics refers to the optimization of social technical systems, including their organizational structures, policies and processes. The relevant topics include communications, management of resources, work projects, temporal organization of work, team work, participative project, new work paradigms, cooperative work, organizational culture, network organizations and quality management (IEA, 2000). The purpose of this study was the reorganization of the methods and processes of the occupational health sector (SMS/SO - Portuguese acronym of the area) of a petrochemical company. The work involved thirty professionals: a coordinator, two occupational physicians, one cardiologist, one occupational dentist, two occupational nurses, eleven occupational health technicians, one social worker, one nutritionist, one phonoaudiologist, one ophthalmologist, one biochemist, two ergonomists, three administrative assistants, one administrator and one psychologist, during a six-month period. The methodology that was used sought to establish a cooperative alliance focused on change, transformation and acquisition of skills, reflecting directly on the attitudes and performance of the leaderships and their work teams. In addition to the feedback practice, the following supporting tools were used for the study's success: "Functional Polyvalence Matrix", "Management of Failures", 5W2H", "6M", "5 Why" and "process mapping". The intended results after the organization ergonomics restructuring process will allow the leader to help his or her team to make a diagnosis of the problems, identify options, develop strategies, establish targets and action plans, remove barriers, review contexts and implement the business management fundaments: planning, organization, management, coordination and control. The transformation possibilities allow us to consider some hypothesis: Before: Focus only on results. After: Engage collaborators to create sustainable results. Before: Operating profile. After: Tactical/strategic profile. Before: Find errors. After: Value effort and development. Before: Listen to what is being said. After: Understand what is being said. Before: Create fears of the consequences. After: Create room for risk. Before: Be the one who approves and decides. After: Be the cooperative support. PMID- 22317147 TI - Ergonomics program management in Tucurui Hydropower Plant using TPM methodology. AB - This paper aims to present the benefits achieved in the ergonomics process management with the use of the TPM methodology (Total Productive Maintenance) in Tucurui Hydropower Plant. The methodology is aligned with the corporate guidelines, moreover with the Strategic Planning of the company, it is represented in the TPM Pillars including the Health Pillar in which is inserted the ergonomics process. The results of the ergonomic actions demonstrated a 12% reduction over the absenteeism rate due to musculoskeletal disorders, solving 77,0% of ergonomic non-conformities, what favored the rise of the Organizational Climate in 44,8%, impacting on the overall performance of the company. Awards confirmed the success of the work by the achievement of the Award for TPM Excellence in 2001, Award for Excellence in Consistent TPM Commitment in 2009 and more recently the Special Award for TPM Achievement, 2010. The determination of the high rank administration and workers, allied with the involvement/dynamism of Pillars, has assured the success of this management practice in Tucurui Hydropower Plant. PMID- 22317148 TI - Analysis of mental workload of electrical power plant operators of control and operation centers. AB - Electrical systems can be categorized as critical systems where failure can result in significant financial loss, injury or threats to human life. The operators of the electric power control centers perform an activity in a specialized environment and have to carry it out by mobilizing knowledge and reasoning to which they have adequate training under the terms of the existing rules. To reach this there is a common mental request of personnel involved in these centers due the need to maintain attention, memory and reasoning request. In this sense, this study aims to evaluate the Mental Workload of technical workers of the Control Centers of Electrical Energy. It was undertaken a research on operators control centers of the electricity sector in Northeast Brazil. It was used for systematic observations, followed by interview and application of the instrument National Aeronautics and Space Administration Task Load Index known as NASA-TLX. As a result there will be subsidies for an assessment of mental workload of operators, and a contribution to improving the processes of managing the operation of electric utilities and the quality of workers. PMID- 22317149 TI - The alarm system and a possible way forward. AB - The aim of this paper is to make a review of studies concerning problems with alarm systems and to make a theoretical analysis of these problems. The aim is also to show some general design ideas to improve alarm presentation in process descriptions. Using research results from situation awareness and decision making a number of suggestions for further development of alarm systems are presented. Recommendations include providing operators of complex systems feedback that can support their mental models and situational awareness. Furthermore a recommendation is to design alarm systems that can learn from experience. PMID- 22317150 TI - HMI conventions for process control graphics. AB - Process operators supervise and control complex processes. To enable the operator to do an adequate job, instrumentation and process control engineers need to address several related topics, such as console design, information design, navigation, and alarm management. In process control upgrade projects, usually a 1:1 conversion of existing graphics is proposed. This paper suggests another approach, efficiently leading to a reduced number of new powerful process graphics, supported by a permanent process overview displays. In addition a road map for structuring content (process information) and conventions for the presentation of objects, symbols, and so on, has been developed. The impact of the human factors engineering approach on process control upgrade projects is illustrated by several cases. PMID- 22317151 TI - Development of an expert system for abnormal operating procedures in a main control room. AB - The study was conducted from the perspective of human factors engineering in order to compare the process that operators originally used to diagnose potential and actual faults with a process that included an expert system for diagnosing faults. The results of the study indicated that the existence of an expert system for fault diagnosis makes the task of fault diagnosis easier and reduces errors by quickly suggesting likely Abnormal Operating Procedures (AOPs). PMID- 22317152 TI - Transfer of control system interface solutions from other domains to the thermal power industry. AB - In a thermal power plant the operators' roles are to control and monitor the process to achieve efficient and safe production. To achieve this, the human machine interfaces have a central part. The interfaces need to be updated and upgraded together with the technical functionality to maintain optimal operation. One way of achieving relevant updates is to study other domains and see how they have solved similar issues in their design solutions. The purpose of this paper is to present how interface design solution ideas can be transferred from domains with operator control to thermal power plants. In the study 15 domains were compared using a model for categorisation of human-machine systems. The result from the domain comparison showed that nuclear power, refinery and ship engine control were most similar to thermal power control. From the findings a basic interface structure and three specific display solutions were proposed for thermal power control: process parameter overview, plant overview, and feed water view. The systematic comparison of the properties of a human-machine system allowed interface designers to find suitable objects, structures and navigation logics in a range of domains that could be transferred to the thermal power domain. PMID- 22317153 TI - Participatory ergonomics for psychological factors evaluation in work system design. AB - It is a well recognized understanding that workers whose voice needs to be heard should be actively encouraged as full participants and involved in the early design stages of new ergonomic work system which encompass the development and implementation of new tools, workplaces, technologies or organizations. This paper presents a novel participatory strategy to evaluate three key psychological factors which are respectively mental fatigue, spiritual stress, and emotional satisfaction in work system design based on a modified version of Participatory Ergonomics (PE). In specific, it integrates a PE technique with a formulation view by combining the parallel development of PE strategies, frameworks and functions throughout the coverage of the entire work system design process, so as to bridge the gap between qualitative and quantitative analysis of psychological factors which can cause adverse or advantageous effects on worker's physiological and behavioral performance. PMID- 22317154 TI - Effect of ergonomic and workstyle risk factors on work related musculoskeletal disorders among IT professionals in India. AB - 'Workstyle' can be described as a mechanism by which ergonomic and psychosocial risk factors interact to affect the development, exacerbation and/or maintenance of upper limb pain and functional limitations. Workstyle is associated with the increase in the work demand. In today's life use of computer in the workplace is very common and it causes to increase the work demand among the workers who are working with computer. As work demand increase, according to the characteristic of workstyle, risk of the development of musculoskeletal disorders also increased. This study aimed at to findout the association between ergonomics risk factors, workstyle and WRMSD. Two hundred IT professionals participated in this study. Result revealed that most prevalenet body regions were lower back (20%), Upper back (16%) and shoulder (14%). Study result says that there is a positive association between workstyle score with musculoskeletal pain (r=0.85). Also it revealed that posture and regional pain is associated (r=0.62), per day use of computer and musculoskeletal pain (r=0.46), micro breaks and pain (r=0.87) and productivity and the pain (r=0.95). This study further validates these observations and extends support for the assessment of working postures and workstyle behaviors during the design of WMSD treatment. PMID- 22317155 TI - Slaughterhouse workers exposed to cold: proposal of reference thermography values for hands. AB - The cold environment is an indispensable for slaughtering and processing in the poultry industry In field studies it was observed that a large percentage of workers of this sector have hand contact with the cold chicken and / or frozen, have high complaints prevalence of pain and discomfort, mostly in the hands. The contact of human skin with a cold surface may cause pain, numbness and risk of skin damage. Currently, although the use of infrared thermal imaging has been useful in identifying normal and abnormal patterns of heat distribution on the surface of the body. However your use for work tasks and to assess the potential development of injuries related to it has been limited. Based on the physiological responses can be objectively evaluate the effects of the task demands of work and thus contribute to the development of effective strategies for ergonomic intervention. The methodology will be used to evaluate the subjective thermal sensation with analogue scale of ASHRAE and the infrared thermography in the dorsal and palmar hands. Thus the objective of this research is to propose reference values for thermographic hands within limits of comfort. PMID- 22317156 TI - Psychological determinants of information searching activity. AB - The paper deals with the application of the activity theory in describing psychological determinants of the information searching activity. The notions of information behavior, information retrieval, information competence, information retrieval activity given in Russian and English scientific literature are compared. The research approach to the information retrieval activity based on the principles developed in the Russian theory of activity is described; and the fundamentals of G. Sukhodolsky's generalized conception of activity are presented for the first time. Analysis of empirical researches showed that specific features of information search depend on how the user evaluates information resources, information, conditions and results of search. Psychological determiners of information search may be detected as the system of evaluative alternatives, which is generated by the user during the process of his experience growth. We discovered that user's evaluation system is also related to his individual typological and personal regulative features and determines the choice of the search strategy. PMID- 22317157 TI - Minor psychiatric disorders among nursing workers--is there an association with current or former night work? AB - We aimed at analyzing whether Minor Psychiatric Disorders (MPD) is associated to night work either currently or in the past. A cross-sectional study was conducted at three public hospitals in Brazil, with female nursing workers. Data collection (N=1,134) was based on a comprehensive questionnaire that included the self reported questionnaire (SRQ-20) for screening of MPD. Former night workers were subdivided into three groups according to their reasons for leaving night work: (i) directly related to work, (ii) related to better reconcile with studies or another job, and (iii) related to health, sleep, fatigue or stress. Binomial logistic regression was performed, with adjustment for potential confounders. A dose response gradient was observed between current night work and MPD (OR=1.5; 95% CI: 1.1-2.2 and OR=2.1; 95%CI: 1.5-3.1 for those who worked up to five nights and six or more nights per 2-week span, respectively). Potential detrimental effects of night work were confirmed. The association between working at night and MPD was not restricted to current night workers as workers who left night work for health/fatigue/sleep/strain also showed higher chances of reporting MPD (OR=1.8;95%CI:1.14-2.90). Results contribute to the scientific debate on the impact of night work on health and wellbeing. PMID- 22317158 TI - Concurrent cognitive task may improve motor work performance and reduce muscle fatigue. AB - Performance of certain cognitive tasks either during physical load or in rest pauses between boosts might lead to slowing of muscle fatigue and fatigue related decline in performance. Seventeen right-handed healthy volunteers (age 24 +/- 1.4, 8 males) participated in this study, aiming to investigate the effect of the level of the cognitive information processing - 1) passive perception of audio stimuli, 2) active stimuli discrimination, 3) active stimuli discrimination following motor response - on motor task performance (handgrip test 30% and 7% of MVC) and muscle fatigue development. Cognitive tasks show the following effects on motor work: i) Perceived fatigue during 30 % MVC (fatiguing) condition developed slower if participant pressed button in response to deviant acoustic stimuli, as compared to passive listening. Counting task, an active task without motor component, took the intermediate position and did not differ significantly from two other cognitive tasks. ii) MVC after 30% MVC (fatiguing) condition tended to decrease stronger when accompanied with passive listening in comparison with both active tasks. iii) Motor task performance during 30% MVC (fatiguing) condition was better for active cognitive task with motor component than for passive task. Active task without motor component took the intermediate position and did not differ significantly from both the other cognitive tasks. PMID- 22317159 TI - Effects of physical and mental demands on shoulder muscle fatigue. AB - Mental demands have been associated with increased risk of injuries; however, its influence on muscle fatigability remains unclear. The aim of this study was to investigate the interaction of mental workload and physical workload on muscle fatigability during repetitive shoulder work. Twelve young participants, balanced by gender, performed shoulder abduction exercises until exhaustions at three levels of physical workload (low (5% maximum voluntary contraction (MVC)), moderate (35% MVC), and high (55% MVC)) in the absence and presence of a mental arithmetic test. Endurance time and rate of strength decline were employed as indicators of muscle fatigue. Concurrent physical and mental processing was found to adversely decrease muscle endurance by ~25% at the moderate intensity level. Furthermore, concurrent demands were associated with faster rate of strength decline compared to the control, irrespective of the physical intensity level. Findings from the current study provide evidence of the adverse effects of mental workload on muscle capacity (i.e., endurance and fatigue). It is therefore important to consider potential changes in worker capacity with concurrent physical and cognitive demands before designing work tasks/products. PMID- 22317160 TI - False alarms and incorrect rejections in an information security center: correlation with the frequency of incidents. AB - This study examines the actions taken by operators aimed at preventing and combating information security incidents at a banking organization. The work utilizes the theoretical framework of ergonomics and cognitive psychology. The method is workplace ergonomic analysis. Its focus is directed towards examining the cognitive dimension of the work environment with special attention to the occurrence of correlations between variability in incident frequency and the results of sign detection actions. It categorizes 45,142 operator decisions according to the theory of signal detection (Sternberg, 2000). It analyzes the correlation between incident proportions (indirectly associated with the cognitive efforts demanded from the operator) and operator decisions. The study demonstrated the existence of a positive correlation between incident proportions and false positive decisions (false alarms). However, this correlation could not be observed in relation to decisions of the false-negative type (incorrect rejection). PMID- 22317161 TI - Occupational stress, working condition and nutritional status of military police officers. AB - This study aimed to investigate the relationship between stress, working conditions and the nutritional status of 53 military police officers in a Southeast city of Brazil. In order to evaluate the symptomatology and the stress phase, the Inventory of Stress Symptoms Lipp for Adults - ISSL was utilized. The assessment of the working conditions was performed by means of socio-demographic questionnaire, direct observation and interviews. The nutritional and health conditions were assessed through anthropometric measures, biochemical tests, blood pressure measurements and cardiovascular disease risk calculator. The sample is of the male gender (92.5%) and aging below 40 years old (73.6%). From these, 35.8% showed stress and 68.4% were in the resistance phase, with 31.6% almost burned out. Through the calculation of Chi-square we could find positive association between the BMI and tiredness (P = 0.0188), between the BMI and irritation (P = 0.0005) and the BMI and the appearance of nervous system problems or emotional problems (P = 0.0304), indicating that these statuses or problems could be related to work. We can conclude then, the stress is present among military police officers. No case of critical stress was found, and the stress phases identified are still susceptible to intervention. PMID- 22317162 TI - Interventions to improve patient safety in transitional care--a review of the evidence. AB - When a patient's transition from the hospital to home is less than optimal, the repercussions can be far-reaching - hospital readmission, adverse medical events, and even mortality. Elderly, especially frail older patients with complex health care problems appear to be a group particularly at risk for adverse events in general, and during transitions across health providers in particular. We undertook a systematic review to identify interventions designed to improve patient safety during transitional care of the elderly, with a particular focus on discharge interventions. We searched the literature for qualitative and quantitative studies on the subject published over the past ten years. The review revealed a set of potential intervention types aimed at the improvement of communication that contribute to safe transitional care. Intervention types included profession-oriented interventions (e.g. education and training), organisational/culture interventions (e.g. transfer nurse, discharge protocol, discharge planning, medication reconciliation, standardized discharge letter, electronic tools), or patient and next of kin oriented interventions (e.g. patient awareness and empowerment, discharge support). Results strongly indicate that elderly discharged from hospital to the community will benefit from targeted interventions aimed to improve transfer across healthcare settings. Future interventions should take into account multi-component and multi-disciplinary interventions incorporating several single interventions combined. PMID- 22317163 TI - Radiological emergency response for community agencies with cognitive task analysis, risk analysis, and decision support framework. AB - Radiological nuclear emergency responders must be able to coordinate evacuation and relief efforts following the release of radioactive material into populated areas. In order to respond quickly and effectively to a nuclear emergency, high level coordination is needed between a number of large, independent organizations, including police, military, hazmat, and transportation authorities. Given the complexity, scale, time-pressure, and potential negative consequences inherent in radiological emergency responses, tracking and communicating information that will assist decision makers during a crisis is crucial. The emergency response team at the Angra dos Reis nuclear power facility, located outside of Rio de Janeiro, Brazil, presently conducts emergency response simulations once every two years to prepare organizational leaders for real-life emergency situations. However, current exercises are conducted without the aid of electronic or software tools, resulting in possible cognitive overload and delays in decision-making. This paper describes the development of a decision support system employing systems methodologies, including cognitive task analysis and human-machine interface design. The decision support system can aid the coordination team by automating cognitive functions and improving information sharing. A prototype of the design will be evaluated by plant officials in Brazil and incorporated to a future trial run of a response simulation. PMID- 22317164 TI - Supporting the scholar role in intensive care nursing. AB - This study investigates how future informatics applications can support and challenge intensive care nurses (ICU nurses) to grow and learn continuously. To this end a research-and-design tool is introduced which is based on a model of the nursing process that starts from the idea that a nurse fulfills three different roles: the role of practitioner (using information immediately to base actions upon), the role of scholar (using information later on to learn from) and the role of human (coping with stress and dealing with emotions). In this paper the focus is on the scholar role. Twenty-eight intensive care staff members from six different hospitals were asked to recount an imposing experience from the perspective of each role. Regarding the scholar role, the participants mentioned 77 learning strategies they adopt for individual as well as organizational learning. Individual learning concerned reflection on former patient cases, reflection on current patient cases to anticipate a change in the patient's condition and reflection on personal behavior and decisions. Organizational learning concerned reflection on former patient cases. Examples of specific strategies were formal team evaluations focused on procedure and understanding the perspective of team members, being present at autopsies, and giving feedback on the nursing skills of colleagues. Based on these strategies design implications are defined for future nursing informatics applications, which will be presented. PMID- 22317165 TI - Handover process: how to improve quality and safety through an ergonomic solution. AB - Patient safety practices for enhancing the quality and safety of handover are context sensitive interventions. In this article we explore the use of cultural probes as a qualitative technique with a twofold objective: eliciting implicit activity pattern and tools that may constitute resources for the design of effective handover solutions and prompting health care practitioners' participation and involvement. PMID- 22317166 TI - The actuation of physiotherapy in the certifications of occupational quality, health and safety. AB - To be distinguished from other companies, organizations are searching norms of certifications, such as ISO 9001, OHSAS 18001 and BS 8.800 to become more competitive in the work market, offering health and safety to the worker and quality to the customer. This extends the performance field of the Physiotherapist, who can use their knowledge to favor the processes of implementation of these certifications. The present work aims to identify the performance of the Physiotherapist in such processes of certification, as well as to verify their knowledge concerning the norms of certification and the performance in the occupational environment. METHODOLOGY: The population was constituted by the physiotherapists who had participated at the 4 degrees FISIOTRAB, the sample was composed by 30 physiotherapists, a questionnaire with pertinent questions to the study was applied. RESULTS: 34% of the interviewed did not know what OHSAS 18001 and ISO 14001 were, 66% did not know about the BS 8,800 certification. 76% of the interviewed had never participated in the implementation of certification norms; among those who had participated 28% were present during the implementation of ISO 9001, 57% at the implementation of OHSAS 18001 and 15% at that of both OHSAS and ISO 14001 together. Given that, from the 24% that had already acted in such implementations, 70% possess a specific formation in Occupational Physiotherapy. CONCLUSION: It was verified that the least part of physiotherapists have acted during the implementation of certification norms, and that even when they work in the Occupational Physiotherapy field many do not possess a deep knowledge on the different practical performances. PMID- 22317167 TI - Job strain in different types of employment affects the immune response. AB - The immune system, in cooperation with neuroendocrine functions, defends from cancer and infections mainly by the activity of blood natural killer (NK) cells. Blood NK activity may be influenced by the type of employment since work is the central part of life; moreover, job stress is a situation affecting both neuroendocrine and immune systems. This study examines anxiety (by STAI 1 and 2), job strain (by the Karasek's JCQ) and blood NK activity (by an in vitro radio isotopic method) of 134 male workers. These men, over 38 years old with stable employment, were working in factories, in construction yards, in offices, as hospital attendants or as self-employed craftsmen. Workers in factories and in construction yards, with high job strain, showed lower NK activity, while office employees, with low job demand, and craftsmen with low anxiety and elevated decision latitude, showed higher NK activity; the level of NK activity of the hospital attendants was between the other groups. In conclusion, this study confirms that the type of employment, related to job stress, affects blood NK activity. Moreover, blood NK activity may be used in the bio-monitoring of workers at high risk. PMID- 22317168 TI - Job stress and productivity increase. AB - This paper examines mental and physical pressures that workers bear at work. The authors discuss how on the-job stress affects a person's capabilities and productivity, and how such pressures lend to higher incidences of accidents at work. The paper also discuss methods of reducing job-related stress and increasing productivity. An intervention was conducted amongst workers in a private firm. It shows mental and emotional pressure can affect performance and productivity of a worker on the job. One of the biggest influences of today's worker is on the-job stress. Job stress occurs when the requirements of the job do not match the capabilities, resources, or needs of the worker. This consequently affects how a person would normally deal with customer service problems, grievances, violence, conflict, and decisions on the job. Stress is an inevitable part of everyday life, and is therefore a distinct part of a person's job. To properly control the outcome of stress, there are certain precautions and methods that should be taken that will boost productivity. PMID- 22317169 TI - Burnout syndrome and Brazilian civil aviation: a short essay on the focus on prevention. AB - INTRODUCTION: At the same time that there are increased demands we have become more sedentary, increasing risk factors for new diseases. All this reflects on our quality of life with special emphasis upon a particular syndrome called Burnout. Aviation is no exception and packed into its processes each day more expeditious, promotes a perfect environment for the development and spread of the syndrome. AIM: To evaluate the quality of life, organizational climate, and the level of physical activity among employees of a Brazilian airline. METHODS: A cross-sectional design was conducted with 8 subjects. RESULTS: Total score on the WHOQOL quality of life questionnaire was 64.7 (SD 10.8), and the environmental field showed the lowest score. Nevertheless, the sedentary risk factor was performed in 25% of the sample. About the organizational climate, it can be seen that 6.12% of the sample was framed in "Professional Exhaustive", 29.60% in the condition of "Warning", and 64.37% in the condition of "Professional Efficiency". CONCLUSION: the study found a low quality of life, especially in the environmental category, sedentary people and a large proportion of employees in this Brazilian airline with negative scores on the Organizational Climate. PMID- 22317170 TI - Is occupational stress associated with work engagement ? AB - The occupational stress is associated with dissatisfaction, excessive demand at work and personal factors. Those factors can reduce work performance and can predispose workers to various diseases. Workers' health may be protected if there is encouragement to face challenges, which may lessen the impact on psychological and somatic stress and thus have greater personal and professional satisfaction. The aim of this study was to evaluate the association between occupational stress and work engagement. Participated in this study 457 male and female workers of a metallurgical industry. Subjects answered personal data, and the Job Stress Scale and Utrecht Work Engagement Scale were applied. Results showed an association between occupational stress and work engagement (P=0,001). The way the individual deals with his frustrations, or rather the work engagement, is associated with the occupational stress. PMID- 22317171 TI - Occupational stress and biomechanical risk in a high fashion clothing company. AB - Psychosocial discomfort may amplify job-related risk factors. The aim of this study is to evaluate job stress in a high fashion clothing company with upper limb biomechanical overload due to repetitive and forceful manual activities. Biomechanical risk was analyzed and in part reduced using the OCRA Check list. A total of 518 workers (433 females and 85 males) were investigated to determine anxiety (by STAI 1 and 2), occupational stress (using the Italian version of the Karasek Job Content Questionnaire) and perception of symptoms. Final biomechanical assessment did not reveal high risk jobs, except for cutting. Although the perception of anxiety and job insecurity was within the normal range, all the workers showed a high level of job strain (correlated with the perception of symptoms) due, probably, to very low decision latitude. It was suggested that job strain may increase the perception of symptoms. Moreover, the result of this study indicates that musculoskeletal overload has to be further analyzed since its low level is not in agreement with the level of discomfort due to the repetitive tasks. PMID- 22317172 TI - Comparison between occupational noise measurement strategies: why is it important? AB - The international standard ISO 9612:2009, regarding the determination of occupational noise exposure through an engineering method, establishes a methodology for evaluating the exposure of workers to occupational noise, through the specification of three different strategies, namely: task-based measurement (TBM); job-based measurement (JBM) and; full day measurement (FDM). In this work, questions are raised, "resulting in a literature review regarding the need to test the functionality of the three strategies, through the systematic comparison between them and analysis of their application impact at several levels. There is a need to test the compare these three strategies, since there are no peer-review studies in this domain. In fact, there are still no studies that systematically do the comparison between them and analyze the impact of their application at various levels, such as the precision and accuracy of the results, the required equipment, time spent and, most important, the estimation of the uncertainty associated to the measurements. PMID- 22317173 TI - SCANAM method for the assessment of industrial noise. AB - Work in an industrial environment is often associated with high levels of noise. For measuring and evaluating of noise levels, sometimes it is necessary to use several instruments. These instruments can be very expensive and require qualified personnel. Medium and small-sized firms often lack sufficient financial resources to ensure continuous measurement and assessment of noise levels. For this reason, a new SCANAM method for assessing the levels of noise is designed. This method involves the use of cheap and accurate sound level meter and specially designed software for assessing the effects of noise. Application of this method is very simple. Based on a noise sample in duration of eight hours, the accuracy of the SCANAM method was confirmed. Application of this method is significantly cheaper than an approach based on the use of expensive multi function devices, or separate devices for measuring and assessing noise at the workplace. PMID- 22317174 TI - Analysis of noise on construction sites of high-rise buildings. AB - In the civil construction industry sector, it has been observed that the increasing use of machines has made tasks noisier and consequently caused hearing loss and had other adverse effects on workers. The objective of this study was to identify and assess the physical risks of noise present in activities undertaken in a construction company in order to propose control measures which will contribute to the management of health and safety within the company's organization. The methodology applied was based on verifying the characteristics of exposure to noise on construction sites, from an observation of sources which generated noise and making measurements of sound pressure levels emitted by these sources. The data was then analyzed and compared with the recommended performance levels established in control measures. As a result, it was found that some machines and equipment used in civil construction often generate noise above the acceptable levels and as such, in these cases, various control measures have been proposed. It is believed that the use of management techniques is the most effective way to assess risk and to implement the preventive and corrective actions proposed, and allows for the analysis of sound pressure levels on an ongoing basis. PMID- 22317175 TI - The binomial work-health in the transit of Curitiba city. AB - The working activity in traffic of the big cities complex interacts with the environment is often in unsafe and unhealthy imbalance favoring the binomial work - health. The aim of this paper was to analyze the relationship between work and health of taxi drivers in Curitiba, Brazil. This cross-sectional observational study with 206 individuals used a questionnaire on the organization's profile and perception of the environment and direct observation of work. It was found that the majority are male, aged between 26 and 49 years and has a high school degree. They are sedentary, like making a journey from 8 to 12 hours. They consider a stressful profession, related low back pain and are concerned about safety and accidents. 40% are smokers and consume alcoholic drink and 65% do not have or do not use devices of comfort. Risk factors present in the daily taxi constraints cause physical, cognitive and organizational and can affect your performance. It is concluded that the taxi drivers must change the unhealthy lifestyle, requiring a more efficient management of government authorities for this work is healthy and safe for all involved. PMID- 22317176 TI - How can occupational health services in Sweden contribute to work ability? AB - Occupational health service in Sweden is often described as an important and strategic resource to reduce work-related diseases, improve work ability and successfully assess improvement of the workplace. However, not much research has been done on how OHS contribute to reduced absence due to work-related illness or improvement of the work ability of employees. In our study, the ambition has been to describe how OHS can contribute and give effects in client companies. Fifteen companies considered to be good examples were selected in cooperation with the social partners. Semi-structured interviews were carried out with representatives of the company and OHS. The results show that efficient collaboration depend strongly on the relationship between the OHS and the company, and were highly correlated with a continuously dialogue and contact. Good occupational safety and health management at company level was a key factor for effective use of OHS. The strategic collaborations also often led to that OHSs contribution was gradually shifted from a reactive or medical focus to a more proactive approach. Several of the interviewed OHSs also held this strategy to work more with prevention, and focusing on "treating the organization", not the individual, leaving the executive measures to the company. PMID- 22317177 TI - Order-picking in deep cold--physiological responses of younger and older females. Part 1: heart rate. AB - The sales figures of chilled and frozen food have been rising steadily over the years. Naturally, this has also led to an increase in the number of jobs related to these goods. While these workplaces are becoming more and more important there are, nevertheless, only a few investigations into the effects of working in deep cold on humans. Order-picking in a cold environment represents a high workload. Especially working at -24 degrees C with wearing heavy cold protective clothing leads to explicitly higher strain. Since performance decreases with age, varying physical strain between younger and older employees can hypothetically be expected. In order to quantify the physiological responses to working in the cold, 15 subjects of two female age groups, each, (20- to 35-year-olds and 40- to 65-year-olds) were asked to carry out whole working day tasks in a chill room (+3 degrees ) and in a cold store (-24 degrees C). Simultaneously, heart rate and other physiological relevant parameters were measured. PMID- 22317178 TI - Order-picking in deep cold--physiological responses of younger and older females. Part 2: body core temperature and skin surface temperature. AB - So far, it was unclear to what extent working in deep cold-storage depots has an influence on female order-pickers body core temperature and skin surface temperature considering different age groups. Physiological effects of order picking in a chill room (+3 degrees C) and cold store (-24 degrees C) were examined on 30 female subjects (Ss), classified in two age groups (20- to 35- year-olds and 40- to 65-year-olds). The body core temperature was taken every 15 min at the tympanum and the skin surface temperature was recorded continuously at seven different positions. Working in the chill room induced a decrease of the body core temperature up to 0.5K in comparison to the value at the outset for both age groups which could be compensated by all Ss during the breaks. Working in the cold store caused a decline up to 1.1K for the younger Ss and 1.3K for the older Ss. A complete warming-up during the breaks was often not possible. Regarding the skin surface temperature, working in the chill room can be considered as unproblematic, whereas significantly lower temperatures at nose, fingers and toes, associated with substantial negative subjective sensations, were recorded while working in the cold store. PMID- 22317179 TI - System modeling with the DISC framework: evidence from safety-critical domains. AB - The objective of this paper is to illustrate the development and application of the Design for Integrated Safety Culture (DISC) framework for system modeling by evaluating organizational potential for safety in nuclear and healthcare domains. The DISC framework includes criteria for good safety culture and a description of functions that the organization needs to implement in order to orient the organization toward the criteria. Three case studies will be used to illustrate the utilization of the DISC framework in practice. PMID- 22317180 TI - The effect on employees of violence climate in the workplace. AB - Violent incidents in the workplace which negatively affect employees' health and safety present an important problem of health and safety at work. This study aimed to determine the effects of the violence prevention climate on employees' job satisfaction and stress by determining how they perceive the dimensions of the violence climate. The participants in this study were 240 employees in various sectors (health, service, etc.) in Turkey. The study used the 18 item Violence Prevention Climate scale developed by Kessler et al (2008) translated into Turkish. The mean age of the participants was 32.3 +/- 9.53, mean working years 9.1 +/- 8.02. According to the correlation analysis results, the violence prevention climate dimensions of policies, practices and pressure for unsafe practices were found to have a positive significant relationship with job satisfaction. A significant negative correlation was determined between policies and practices and depression. A significant negative correlation was determined between practices and stress. The stepwise regression analysis results determined a significant relationship between pressure and job satisfaction. The stepwise regression analysis results also determined a significant relationship between the dimension of practices and depression. However, the established regression model was found not to be statistically significant in terms of stress and anxiety dependent variables. PMID- 22317181 TI - Indicators of healthy work environments--a systematic review. AB - The purpose of this study was to systematically review the scientific literature and search for indicators of healthy work environments. A number of major national and international databases for scientific publication were searched for research addressing indicators of healthy work environments. Altogether 19,768 publications were found. After excluding duplicates, non-relevant publications, or publications that did not comply with the inclusion criteria 24 peer-reviewed publications remained to be included in this systematic review. Only one study explicitly addressing indicators of healthy work environments was found. That study suggested that the presence of stress management programs in an organization might serve as indicator of a 'good place to work', as these organizations were more likely to offer programs that encouraged employee well being, safety and skill development than those without stress management programs. The other 23 studies either investigated employee's views of what constitute a healthy workplace or were guidelines for how to create such a workplace. Summarizing, the nine most pronounced factors considered as important for a healthy workplace that emerged from these studies were, in descending order: collaboration/teamwork: growth and development of the individual; recognition; employee involvement; positive, accessible and fair leader; autonomy and empowerment; appropriate staffing; skilled communication; and safe physical work. PMID- 22317182 TI - Effects of vibration exposure on professional drivers: a field test for quantifying visual and cognitive performance. AB - Effects of whole-body vibration (WBV) exposure on professional drivers were predicted using a 45 subjects sample of healthy volunteers from both genders. These volunteers preformed a visual/motor accuracy evaluation test, the 'omega test', inside a vehicle (van) under three different WBV exposure conditions, van halted, van performing a circuit on asphalt, and on cobblestone. WBV levels of the stated conditions were statistically different and impairment upon subjects' performance was found. The statistical significant difference encountered between the subjects performance under the two whole-body vibration profiles (asphalt and cobblestone), seems to indicate that the vibration levels also represent a variable to be taken under consideration. No gender related difference was found. PMID- 22317183 TI - In regulation we trust. AB - The role of trust has been argued to play an increasingly important role in modern, complex, and ambivalent risk societies. Trust within organizational research is anticipated to have a general strategic impact on aspects such as organizational performance, communication and knowledge exchange, and learning from accidents. Trust is also an important aspect related to regulation of risk. Diverse regulatory regimes, their contexts and risks influence regulators use of trust and distrust in regulatory practice. The aim of this paper is to discuss the relationship between risk regulation and trust across diverse risk regulation regimes. By drawing from studies of risk regulation, risk perception, and trust the purpose is to discuss how regulation and trust are linked and used in practice to control risk across system levels in socio-technical systems in high risk industries. This paper provides new knowledge on 1) how functional and dysfunctional trust and distrust are grounded in the empirical realities of high risk industries, 2) how different perspectives on trust and distrust act together and bring new knowledge on how society control risk. PMID- 22317184 TI - Whistleblowers: an essential resource for the sustainable prevention of risks in sociotechnical systems. AB - Our world of industry and technology has, over the years, has seen undeniable successes in terms of safety and reliability. But major catastrophes and dramatic accidents continue, even today, to cause major human and material losses and to threaten the environment with pollution on a massive scale. Could these disasters and these accidents have been foreseen and avoided? Would it have been possible to anticipate their occurrence by detecting signals of potential hazards? It is unsettling to notice, through retrospective analysis of such events, that warnings had been issued long before the catastrophe or accident took place. This raises several questions, which we will attempt to address in this paper. Why are whistleblowers often not listened to, threatened, or simply ignored? Why are their warnings viewed as "bad omens" instead of essential resources to ensure safety? Do whistleblowers stand idly by, or do they implement individual and collective strategies to make themselves heard? Which managerial and organizational conditions are conducive to developing empowerment in whistleblowers? Based on four case studies, we attempt to address these questions, and offer a first level of analysis and explanation by proposing and defining two new concepts: operative resilience and strategic resilience. PMID- 22317185 TI - The nexus between OSH and subcontracting. AB - Subcontracting of specialized functions to external companies (e.g. cleaning or maintenance) is actually very common within several industries. These external companies' are called contractors and their contracting is often designated as outsourcing. Frequently contractors involve other companies (the sub-contractors) to assist them in fulfilling the contract, resulting in a complex chain of organizations focused on interchange of work - the contracting chain. Therefore in the same work site can coexist workers form the client-company and workers from the contractors and/or subcontractors. Since contractors perform their job in client's facilities, they can be exposed to hazards that are unknown to them. On other hand, workers of the client company can also be exposed to hazardous situations derived from the work performed by the contractors. The paper discusses how adequate occupational safety and health conditions can be assured when dealing with this kind of dynamic labor networks. Two case-studies and several examples coming from international literature will be presented. PMID- 22317186 TI - Identification of non-technical skills from the resilience engineering perspective: a case study of an electricity distributor. AB - Training in non-technical skills (NTS) does not usually question the design of the work system, and thus focuses narrowly on workers as the unit of analysis. This study discusses how the identification of NTS, a major step for developing an NTS training program, might be re-interpreted from the perspective of resilience engineering (RE). This discussion is based on a case study of identifying NTS for electricians who perform emergency maintenance activities in an electricity distribution power line. The results of the case study point out that four data analysis procedures might operationalize the RE perspective: (a) identifying factors that make the work difficult and which could be integrated into NTS training scenarios; (b) identifying recommendations for re-designing the system, in order either to reduce or eliminate the need for NTS; (c) classifying the NTS into pragmatic categories, which are meaningful for workers; and (d) regarding the identification of NTS as an opportunity to give visibility to adaptations carried out by workers. PMID- 22317187 TI - Structuring of manual of orientations and technical information for laundries of industries of animal products origin. AB - This study looked for to lift information regarding laundries inserted in industries of animal products origin, to understand the activities developed in the section and to structure a Manual of Planning and Technical Information for laundries to industries of animal products origin, with the intention of subsidizing the planning, structuring and control of this work place, because norms or regulations that supervise don't exist or aid their managers and workers as for the operation of this work place. PMID- 22317188 TI - ERGOBERCO(r) (Ergonomics Crib)--evaluation of the prototype for a adaptation to safety's variables and comfort. AB - The crib is the infantile furniture more mentioned in infantile accidents. In spite of the existence of several models, many of them are not appropriate to their users and considered insecure. The objective of this study was to structure the prototype of ERGOBERCO(r), considering technical norms and evaluation in loco of the prototype through structured interview answered by the participants of the research. The prototype was evaluated as safer, resistant and comfortable than the crib used by the mothers and participant users of the study. The aspects with larger acceptance index were the movable grating and the compact base, defined for the users as facilitators of the use and attribute of safety of the prototype. Even the prototype having been very appraised and accept for the users, it will be necessary to restructure the prototype so that the same can still be adapted more the users' needs, being, besides insurance and comfortable, with compatible aesthetic pattern with the expectation of these. PMID- 22317189 TI - Exploring functions of the lost seeking devices for people with dementia. AB - This paper utilized a user-centered design approach as the foundation for technology in dementia care in order to improve the quality of telemedicine service. A status-quo analysis and questionnaire survey were conducted to explore the actual needs of the elders in using the lost seeking devices and the problems they encountered. In total, 37 caregivers for people with dementia were surveyed (20 female, 17 male, M = 50.08, SD = 15.47). The dementia-patients: 16 are male, 21 female (M = 72.75, SD = 10.23). Through analysis and induction, 3 problems were identified: poor information transmission, low user acceptance, individual material security anxiety. 2-4 improvement proposals are suggested for each problem. Most care-givers hope technological products would increase the efficiency and safety, but they also think it's too expensive and lack of computer skills. This result demonstrates the choice of seeking methods depends on the education level of the caregivers and most of them are elders. The concern of data leakage is also related to today's fraud issue, which may be the reason limiting the promotion of electronic products and biometrics. Further research is required, suggesting researchers should pursue improvements in lost seeking design devices in dementia for caregivers. PMID- 22317190 TI - From 'human being' to 'social subject': "unfreezing" ergonomics and the implications for understanding and intervening health-disease process. AB - Ergonomics has been successful in increasing productivity and comfort in the work arena. It has also contributed to reducing occupational accidents. Despite this, ergonomics is frequently limited to understanding the health-disease process related to human-technology interactions, as this process is more complex than what can be understood from an ergonomic evaluation. Recognising this limit, this work ontologically and epistemologically contrasts the notions of 'human being' and 'social subject', and concludes that the study object of ergonomics, or human technology interaction, greatly depends on social aspects that nowadays are not tackled explicitly: route (history), project, structure, agency, motivations and power. It also analyses how participatory ergonomics tacitly includes many of these aspects, including some implications that the change of notion, from 'human being' to 'social subject', brings to the understanding of the health-disease process and the reduction of associated risks during human activities. PMID- 22317191 TI - Risk evaluation and exposure control of mineral dust containing free crystalline silica: a study case at a quarry in the Recife Metropolitan Area. AB - During the production of aggregates at quarry sites, elevated quantities of micro particulate mineral dust are produced in all stages of the process. This dust contains appreciable amounts of free crystalline silica in a variety of forms which, if maintained suspended in the air in the work environment, expose the workers to the risk of developing occupational silicosis, which causes reduced ability to work and potential shortening of lifespan. This study was conducted to qualitatively and quantitatively evaluate workers' exposure to mineral dust containing free crystalline silica at a midsized quarry in the Recife metropolitan area, in the State of Pernambuco. It involved evaluation of the industrial process, collection and analysis of representative dust samples, and interviews with the management team of the company with the intent to assess the compliance of the company with Regulatory Standard (NR) 22--Occupational safety and health in mining. In order to assist the company in managing risks related to dust exposure, three protocols were developed, implemented and made available, the first based on NR 22, from which the company was also given an economic safety indicator, the second based on the recommendations and requirements of Fundacentro to implement a Respiratory Protection Program and, finally, an assessment protocol with respect to the guidelines of the International Labor Organization to implement a health and safety management system. This study also showed the inadequacy of the formula for calculating tolerance limits in Brazilian legislation when compared with the more strict internationally accepted control parameters. From the laboratory results, unhealthy conditions at the quarry site were confirmed and technical and administrative measures were suggested to reduce and control dust exposure at acceptable levels, such as the implementation of an occupational health and safety management system, integrated with other management systems. From these assessments it is hoped that the proposals can assist the company in developing mechanisms for management and control of dust exposure risks that may improve environmental quality and the well-being of workers. PMID- 22317192 TI - Design for worksystem safety using employees' perception about safety. AB - In this paper, the predictors of work injuries based on Leamon's Man-Machine model are identified in a sociotechnical framework. Several hypotheses are developed and tested to describe the accident/injury phenomena in mining worksystems. Possible designs for improving work-system's safety are specified using scaled Mahalanobis distance (MD). A case control study design is adopted. Five variables namely, age, negative-affectivity, physical-hazards, job dissatisfaction, and safety-practice are emerged as significant contributors to work injuries for the mines studied. Two most interesting findings obtained through this study are (i) 36% of cases (injured employees) (MD < 1) are unlucky to meet an accident and (ii) 40% of the controls (non-injured employees) (MD > 1) are lucky to be able to avoid an accident. The most probable reason for the former case is the organizational ineffectiveness while that for the latter may be risky adventures of employees which are due to lack of education, awareness, and appropriate training. Based on the MD values for cases and controls, possible design guidelines are suggested. The study categorically identifies the accident situations where engineering control, education and training, and other organizational safety measures are to be adopted. PMID- 22317193 TI - Forum: social network for the surveillance and prevention of workplace accidents. AB - In 2008, academic researchers and public service officials created a university extension studies platform based on online and on-site meetings denominated "Work Related Accidents Forum: Analysis, Prevention, and Other Relevant Aspects. Its aim was to help public agents and social partners to propagate a systemic approach that would be helpful in the surveillance and prevention of work-related accidents. This article describes and analyses such a platform. Online access is free and structured to: support dissemination of updated concepts; support on site meetings and capacity to build educational activities; and keep a permanent space for debate among the registered participants. The desired result is the propagation of a social-technical-systemic view of work-related accidents that replaces the current traditional view that emphasizes human error and results in blaming the victims. The Forum uses an educational approach known as permanent health education, which is based on the experience and needs of workers and encourages debate among participants. The forum adopts a problematizing pedagogy that starts from the requirements and experiences of the social actors and stimulates support and discussions among them in line with an ongoing health educational approach. The current challenge is to turn the platform into a social networking website in order to broaden its links with society. PMID- 22317194 TI - Ports of Mucuripe and Pecem, Ceara, Brazil: restructuring process and its impact on workers' health. AB - This paper presents a comparative study of working conditions and health hazards of two ports in the state of Ceara: Mucuripe and Pecem, focusing workers in the various categories involved in the operational activities of the two ports. The aim is to investigate changes implemented by the restructuring process of ports arising from the Port Modernization Act. In the case of Ceara, the organization and control of work at the mentioned ports occur differently: Mucuripe, the oldest port, had to adapt to the changes enforced by the Modernization Act and Pecem, called Port Terminal, inaugurated in 2001, "was born modern". To achieve our objective, we carried out field work, using Ergonomic Work Analysis. Systematic observations were made of the various activities carried out by workers, as well as interviews with managers, workers and trade unionists. Container operations and other activities of the two ports were recorded in film and presented to groups of workers (focus groups) in order to better understand work organization and the main differences in tasks carried out in the two ports. Each reality presents different characteristics regarding port operations, type of work and labor control. Results indicate that due to the technological innovations, the restructuring process reduced some risks, but brought new occupational hazards and intensification of work. PMID- 22317195 TI - From prescribed to real rotations: a means of collective protection for the health of workers in a soft drink factory. AB - This article describes a particular way developed by employees to respond to the constraints of a very restrictive manufacturing plant: the mutual cooperation. Facing a very strict organizational context, the production workers can only rely on themselves to cope with the constraints of work. In this context, a complex system of strategies is deployed, resulting in a work environment governed by the sense of collaboration and mutual cooperation. The objectives of the implemented strategies, however, go beyond the attempts to reduce the work overload. They may be linked to a way of maintaining high levels of productivity and a way for workers to keep their jobs. We hope to contribute, through this study, to the general knowledge of the strategies developed by workers in production lines in order to minimize the pains. PMID- 22317196 TI - Accidents related to the use of products and services in the city of Sao Luis, Brazil. AB - This article presents a study on the accidents related to the use of products and services, as recorded at two emergency hospitals at the city Sao Luis, Brazil. The goal of the study was to evaluate the main types and causes of unintentional accidents as well as the more frequent injuries for further improvement of products and services. The study evaluated the victims profile (gender and age), the circumstances (activity, local and time) that lead to the accidents and the type of resulted injury. Non-parametric statistics showed that 83.64% of the accidents were related to products (57.6% of them being consumer products) and 8.6% are related to maintenance services. 57.6% of the victims were children under 15 years old, and 58.4% were male. 50.2% of accidents occurred at home, more often (44.7%) in the afternoon. The most common injury was musculoesqueletal (48.6%), 49.0% being cranioencephalic trauma and 15.2% fractures. PMID- 22317197 TI - Tragedy on grade crossing: driver failure or systemic fragility? AB - In 2010, an accident occurred in Americana-SP, Brazil, involving two trains and one bus on a Grade Crossing, when 10 people died and 17 were injured including workers. This paper aims to analyze the accident using the Model of Analysis and Prevention of Work Accidents (MAPA). The method provides observation of work, interviews and analysis of documents to understand precedents of the event in the following stages: to understand the usual work from the involved people, the changes occurred in the system, the operation of barriers, managerial and organizational aspects. By the end, measures are suggested to avoid new occurrences. The accident took place at night in a site with insufficient lighting. The working conditions of bus drivers, train operators and watchmen are inadequate. There were only symbolic barriers (visual and acoustic signals) triggered manually by watchman upon train operator radio communication. The fragility of the barrier system associated to poor lighting and short time to trigger the signaling seem to play a critical role in the event. Contrary to the official report which resulted in guilt of the bus driver, the conclusion of the paper emphasizes the fragility of the safety system and the need of level crossing reproject. PMID- 22317198 TI - Human factors identification and classification related to accidents'causality on hand injuries in the manufacturing industry. AB - The causes of occupational accidents from the perspective of human factors have been a subject which has received little attention into the field of scientific research. The aim of this research was to identify and classify the human factors that influence human errors and failures that cause accidents and injuries specifically on hands. Available studies related to the topic have been developed mainly for aerospace applications and are found insufficient to explain accidents causalities in the manufacturing industry. This research was developed in the assembly industry of automotive harnesses and was conducted following a mixed Cognitive Anthropological approach. This study was developed in two phases. During the first qualitative phase, participants freely listed their knowledge to identify elements of the cultural domain, then and in the second phase they performed the successive pile sort technique for the collection data to classify elements in the cultural domain. Statistical models like Cluster Analysis and Multidimensional Scaling were applied for results' validation purposes. As results, 70 different human factors were identified and in the second phase they were classified into 4 main categories which were: human error, unsafe conditions, individual factors, and organizational factors. Statistical methods validated these results. PMID- 22317199 TI - Control centers design for ergonomics and safety. AB - This paper shows the general design conditions about ergonomics and safety for control centers in the petrochemical process industry. Some of the topics include guidelines for the optimized workstation design, control room layout, building layout, and lighting, acoustical and environmental design. Also takes into account the safety parameters in the control rooms and centers design. The conditions and parameters shown in this paper come from the standards and global advances on this topic on the most recent publications. And also the work was supplemented by field visits of our team to the control center operations in a petrochemical company, and technical literature search efforts. This guideline will be useful to increase the productivity and improve the working conditions at the control rooms. PMID- 22317200 TI - Methodological proposal for occupational health and safety actions in research laboratories with nanotechnologies activities. AB - Nanotechnologies is a multidisciplinary set of techniques to manipulate matter on nanoscale level, more precisely particles below 100 nm whose characteristic due to small size is essentially different from those found in macro form materials. Regarding to these new properties of the materials there are knowledge gaps about the effects of these particles on human organism and the environment. Although it still being considered emerging technology it is growing increasingly fast as well as the number of products using nanotechnologies in some production level and so the number of researchers involved with the subject. Given this scenario and based on literature related, a comprehensive methodology for health and safety at work for researching laboratories with activities in nanotechnologies was developed, based on ILO structure guidelines for safety and health at work system on which a number of nanospecific recommendations were added to. The work intends to offer food for thought on controlling risks associated to nanotechnologies. PMID- 22317201 TI - Perceptual load in central and peripheral regions and its effects on driving performance: advertizing billboards. AB - A broadened version of the perceptual load model was utilized to explore systematically the influence of four variables on driver's behavior: a. levels of load on the road; b. levels of load at the sides of the road; c. event's initial location (on the road vs. at the sides of the road); and d. the presence and size of advertizing billboards. 18 participants participated in two experimental sessions in a driving simulator. One of the sessions contained advertizing billboards and the other session did not. The results indicated that billboards can have a considerable effect on various aspects of driving like the time required responding to a potentially dangerous event or simply the number of accidents occurring during driving, but importantly the effect of billboards on driving was modulated by the levels of perceptual load. PMID- 22317202 TI - Effects of pushing height on trunk posture and trunk muscle activity when a cart suddenly starts or stops moving. AB - Unexpected sudden (un)loading of the trunk may induce inadequate responses of trunk muscles and uncontrolled trunk motion. These unexpected perturbations may occur in pushing tasks, when the cart suddenly starts moving (unloading) or is blocked by an obstacle (loading). In pushing, handle height affects the user's working posture, which may influence trunk muscle activity and trunk movement in response to the perturbation. Eleven healthy male subjects pushed a 200 kg cart with handles at shoulder and hip height in a start condition (sudden release of brakes) and a stop condition (bumping into an obstacle). Before the perturbation, the baseline of the trunk inclination, internal moment and trunk extensor muscle activity were significantly higher when pushing at hip height than at shoulder height. After the perturbation, the changes in trunk inclination and internal moment were significantly larger when pushing at shoulder height than at hip height in both conditions. The opposite directions of changes in trunk inclination and internal moment suggest that the unexpected perturbations caused uncontrolled trunk motion. Pushing at shoulder height may impose a high risk of low-back injury due to the low trunk stiffness and large involuntary trunk motion occurring after carts suddenly move or stop. PMID- 22317203 TI - Cognitive structure of occupational risks represented by a perceptual map. AB - The main focus of risk management is technical and rational analysis about the operational risks and by those imposed by the occupational environment. In this work one seeks to contribute to the risk perception study and to better comprehend how a group of occupational safety students assesses a set of activities and environmental agents. In this way it was used theory sustained by psychometric paradigm and multivariate analysis tools, mainly multidimensional scaling, generalized Procrustes analysis and facets theory, in order to construct the perceptual map of occupational risks. The results obtained showed that the essential characteristics of risks, which were initially splited in 4 facets were detected and maintained in the perceptual map. It was not possible to reveal the cognitive structure of the group, because the variability of the students was too high. Differences among the risks analyzed could not be detected as well in the perceptual map of the group. PMID- 22317204 TI - Safety illusion and error trap in a collectively-operated machine accident. AB - Workplace accidents involving machines are relevant for their magnitude and their impacts on worker health. Despite consolidated critical statements, explanation centered on errors of operators remains predominant with industry professionals, hampering preventive measures and the improvement of production-system reliability. Several initiatives were adopted by enforcement agencies in partnership with universities to stimulate production and diffusion of analysis methodologies with a systemic approach. Starting from one accident case that occurred with a worker who operated a brake-clutch type mechanical press, the article explores cognitive aspects and the existence of traps in the operation of this machine. It deals with a large-sized press that, despite being endowed with a light curtain in areas of access to the pressing zone, did not meet legal requirements. The safety devices gave rise to an illusion of safety, permitting activation of the machine when a worker was still found within the operational zone. Preventive interventions must stimulate the tailoring of systems to the characteristics of workers, minimizing the creation of traps and encouraging safety policies and practices that replace judgments of behaviors that participate in accidents by analyses of reasons that lead workers to act in that manner. PMID- 22317205 TI - Human error assessment in electric power company of Serbia. AB - This paper presents a case study which confirmed that the use of APJ for proper assessment of human error in the Electric Power Company of Serbia (hereinafter EPS). The proposal methodological framework was used for human error identification and quantification in the case of a repair intervention on a steel lattice tower 10/0.4 kV (jurisdiction of an EPS subsidiary ED "Jugoistok", Nis, Serbia) which resulted in an accident with a fatal outcome. One of the aims of this study is to show the necessity of human error assessment not only in manufacturing industries but, as it will be shown in this paper, in companies that distribute electric energy, as well. PMID- 22317206 TI - Understanding safety culture by visualization of scenarios--development and evaluation of an interactive prototype. AB - To be able to disseminate knowledge about maritime safety culture and safety management to different actors in the Swedish maritime sector, a preliminary pedagogical concept was developed and evaluated. As a first user group, students at upper secondary maritime schools were chosen and the pedagogical concept was adapted for this group. The concept includes an interactive prototype and a teacher's guide and is based on a model for experience-based learning which connects theory and practice by a cyclic approach. The concept was tested in a classroom setting including interaction with the students and a follow-up one week later. A preliminary evaluation of the results shows a very positive response among the students as well as the lecturers. The educational material was successful in immediately creating a relevant discussion about safety culture, and one week later, students could remember many of the safety scenarios included in the pedagogical concept. PMID- 22317207 TI - Efficient and effective learning for safety from incidents. AB - Learning from incidents is important for improving safety. Many companies spend a great deal of time and money on such learning procedures. The objectives of this paper are to present some early results from a project aimed at revealing weaknesses in the procedures for learning from incidents and to discuss improvements in these procedures, especially in chemical process industries. The empirical base comes from a project assessing organizational learning and the effectiveness of the different steps of the learning cycle for safety and studying relations between safety-specific transformational leadership, safety climate, trust, safety-related behavior and learning from incidents. The results point at common weaknesses in the organizational learning, both in the horizontal learning (geographical spread) and in vertical learning (double-loop learning). Furthermore, the effectiveness in the different steps of the learning cycle is low due to insufficient information in incident reports, very shallow analyses of reports, decisions that focus at solving the problem only at the place where the incident took place, late implementations and weak solutions. Strong correlations with learning from incidents were found for all safety climate variables as well as for safety-related behaviors and trust. The relationships were very strong for trust, safety knowledge, safety participation and safety compliance. PMID- 22317208 TI - Planning crowd events to achieve high participant satisfaction. AB - A case study investigation within a large UK university involving semi-structured stakeholder interviews, examined the organisation, coordination, and security within crowd events of various descriptions. Similarities in approaches and priorities emerged with crowd event organisation, primarily attention to safety requirements, in protecting crowd members, venue reputation, and legal obligations. Conversely, attention to and attitudes and beliefs surrounding user experience, crowd comfort and satisfaction, were often based on personal judgment, and appeared to be influenced by budget considerations. The findings suggest a lack of knowledge and usable evidence based guidance for planning crowd events in relation to important aspects affecting participant satisfaction. PMID- 22317209 TI - Recovery and detachment between shifts, and fatigue during a twelve-hour shift. AB - The study investigated the role of recovery and detachment in the break period between two shifts for fatigue in the current shift. A time-based paper-and pencil diary study was carried out observing sixty-four railway controllers over ten consecutive working shifts. The results demonstrated that fatigue in the current shift was not only affected by recovery and psychological detachment during break phases before a shift, but also by fatigue at shift onset and perceived workload during the shift. PMID- 22317210 TI - How to increase safety in complex systems--an ongoing project. AB - The aim of this paper is to describe an ongoing project with the aim of improving safety in an organization working with maintenance and development of the railway infrastructure in Sweden. The first sub goal was to investigate the General Failure Types in the organization. Seminars and interviews, based on the Tripod Delta method, with 62 employees resulted in a description of these latent errors in the organization. Recommendations for an improvement toward a safety culture was suggested, action plans were formulated and, in some cases, implemented. A follow up study is planned in a two year perspective. PMID- 22317211 TI - Different roles in the quest for system resilience. AB - Into dangerous and complex systems with high degree of interactivity between its components, the variability is present at all time, demanding a high degree of control of its operation. Maintaining or recovering the normality, when the system is under some stress (instability) is a function of Resilience. To cope with prevention, forecast, recovery and with memory of experiences from learned lessons requires some features from the companies. This paper purposes a structure that enables the Total Resilience of a system production that defines the assignments for Workers, Designers and Management Team, according to its features and possibilities. During one year and a half developing studies on ergonomics area of a Brazilian Oil Refinery, several situations were observed and studied using Work Ergonomic Analysis. These situations show actions and strategies that workers use to maintain the system stability. Furthermore, they revealed the importance that these actions are stored in a database of learned lessons from the Company. The research resulted in a broad scheme. It places each of these groups in the process of Total Resilience. It also shows the human like a center of actions that ensure the continuity of the system, main element at Resilience (Anthropocentric View). PMID- 22317212 TI - Circuit board accident--organizational dimension hidden by prescribed safety. AB - This study analyzes an accident in which two maintenance workers suffered severe burns while replacing a circuit breaker panel in a steel mill, following model of analysis and prevention of accidents (MAPA) developed with the objective of enlarging the perimeter of interventions and contributing to deconstruction of blame attribution practices. The study was based on materials produced by a health service team in an in-depth analysis of the accident. The analysis shows that decisions related to system modernization were taken without considering their implications in maintenance scheduling and creating conflicts of priorities and of interests between production and safety; and also reveals that the lack of a systemic perspective in safety management was its principal failure. To explain the accident as merely non-fulfillment of idealized formal safety rules feeds practices of blame attribution supported by alibi norms and inhibits possible prevention. In contrast, accident analyses undertaken in worker health surveillance services show potential to reveal origins of these events incubated in the history of the system ignored in practices guided by the traditional paradigm. PMID- 22317213 TI - Human reliability and ergonomics: a literature review from 1963 to 2011. AB - This study reviews the academic literature on human reliability from the ergonomics perspective. The methodological approach used in this analysis combines several techniques, including bibliometric, content analysis, and social network analysis. The initial sample consisted of 304 articles, which totalized 1,872 citations, published in 94 journals, from the 47-year period between 1963 and 2011. From this initial sample, only 50 articles (16%), totalizing 471 citations are classified as ergonomics area, published in 14 journals, which involve 108 authors, with 471 citations. This sample was expanded via the seminal studies of ergonomics. These articles were coded and tabulated according to their year of publication, the number of publications per journal, major areas of interest, and the relationship between the articles and the research methods discussed. Networks were prepared by keywords, co-citations, and cross-citations. PMID- 22317214 TI - An auditive protection for professional musicians. AB - The auditory channel is one of the most affected by the activity of musicians. The aim of this study was to verify the efficiency of the Monitor of Hearing In Ear regarding prevention of the hearing loss in the activity realized by musicians. This study justifies by the need to verify a possible method of protection for these professionals. It was analyzed a group of 10 musicians of a band of dance of Santa Catarina. The methods of research were questionnaires, audiometry and analysis of the technical specifications of Monitors of Hearing In Ear. The population investigated are aged between 18-56, and time in the profession between 37 and 0,4 years. The exhibition is of, roughly, 12 hours a week during the presentations, 4,5 hours a week rehearsing in group and from 1 to 8 weekly hours of isolated rehearsal. It was observed that 40% of the population presented normal hearing thresholds for left and right ear, the sensorineural hearing loss in the left ear was ascertained in 40% and 20% presented sensorineural hearing loss in both ears. The advantage of the Monitor of Hearing In Ear is that there is the blocking of the undesirable sounds, making possible a greater audible reduction, generally between 25 and 40 dB, showing possibility to be considered a half of protection for professional musicians. PMID- 22317215 TI - Study on the impact of exposure to noise in professional snipers. AB - Facing an increasing violence level and higher firepower in the hands of criminal organizations (especially those related to drug trafficking), the Military Police of Pernambuco has created, in 1989, the "1a Companhia Independente de Operacoes Especiais" (1st Independent Company of Special Operations), as a tactical last resort of the Police to be used on special, complex situations. The CIOE progressively makes use of Negotiation measures, of less-than-lethal maneuvers, of Precision Shots and Tactical Assaults. When all possibilities are drained, the Precision Shot will bring the crisis perpetrator down. This study had as an objective to assess the level of impact noise suffered by the elite snipers of the 1st CIOE-PE in their training. The working conditions of the snipers were evaluated through the use of a semi-structured questionnaire. Noise measuring was done on four (4) .308 IMBEL AGLC (with ammo from the same lot) rifles. Six (6) shots were fired off each gun, separated by a 30-second pause. In the end, it has been concluded that the noise level the 1st CIOE snipers are submitted to is considered to be normal by Brazilian legislation. PMID- 22317216 TI - An exploratory study on the conditions of health, safety and environmental affairs of very small and small-size enterprises in Brazil. AB - This paper focuses on the reality of very small and small enterprises (VSSEs) in Brazil, concerning health and safety management of their workers. These companies tend to operate in a few administrative levels. The owners' health and safety culture is fundamental for the implementation of preventive measures. The VSSEs end up adopting merely reactive and under-the-law actions. In order to understand such reality, a questionnaire was elaborated especially for the research made. Fifty-five very small and small enterprises of the industrial, commercial and service sectors were selected. The research confirmed the reactive attitude shown by the VSSEs, thus demonstrating that none of the companies involved presented policies of safety and health. Even though not holding policies, programs or scopes of their activities, 22% of them revealed to have a clear definition of the responsibilities of their high level administration. Nevertheless, 10% had financial resources allocated to this sector. Such companies do not count on a frequent safety and health support. The ignorance on it leads them to take a reactive action. This study reaches its objective on contributing to the debate, besides indicating that the way to improvement is on the strict cooperation between governments, companies, workers and society. PMID- 22317217 TI - Contributions of participatory ergonomics to the improvement of safety culture in an industrial context. AB - This paper presents the results of an ergonomic intervention conducted within a blast furnace plant. As part of its risk prevention program, the company decided to set up an action plan, in a participatory manner, by setting up working groups to solve health & safety issues. This field mission involved 230 employees, 80 of whom participated actively by being incorporated into working groups. After four months of intervention, a questionnaire survey has been conducted among employees to study the effects of participation on the safety climate. The results seem promising and show that the benefits of participation are numerous: a more positive safety climate associated to safer attitudes and behaviors. However, rather than just participation, it seems to be the employee involvement in the working groups and the satisfaction they derive from their participation that guarantee these positive results. Hence, participatory ergonomics seems to be an effective way to decrease the number of unsafe behaviors at work, provided that the type of participation has been previously well defined and organized according to the specific context of each organization. PMID- 22317218 TI - Mapping of noise impact provoked by the execution of foundation piles at high rise building sites. AB - The objective of this work is to map, in a limited area inside and outside of the worksite, the environmental impact generated by sound pollution coming from the driving of foundation piles for high rise buildings, as well as to observe and check if the noise levels produced by the emitting source are tolerable in the urban environment. The methodology of the work includes a survey of technical references about the subject; measurement of noises surrounding the worksite during the foundation phase for four distinct buildings, with different types of piles: prefabricated piles, continuous helical displacement piles , traditional compaction piles and Terra Probe compaction piles. A grid of points was built due to the time of driving and after that the measurements of environmental noises were performed emitted by the execution of each type of pile using a sound level meter. The interpretation of the measurements and their impacts on the neighborhood of the building were performed using the computational tool Suffer for creating noise level contours. The X and Y axes of the grid represent the distances in meters of the area studied and the Z axis represents the noise measured in dB. The contours developed represent the mapping of the noise at the worksites and their surroundings. The mapping of the urban impact of noise, the measurement of its dimensions, and the examination of its propagation around the building are important subsides to adequate individual and collective protection procedures. Seventy one points were measured at four building sites with different types of piles, and the results showed that at only three points was the noise within the limits of the Municipal Law of Recife of 70 dB, which proves the relevance of the research. Finally, the comparative analysis between the four types of piles shows that the continuous helical displacement pile emits the lowest noise level among the four pile types studied. PMID- 22317219 TI - Ergonomic work analysis as a tool of prevention for the occupational safety and health management system. AB - This paper introduces the Ergonomic Work Analysis as a relevant instrument to identify the risks in occupational environments through the investigation of factors that influence the relationship between the worker and the productive process. It draws a parallel between the several aspects of risk identification in traditional tools of Health and Safety Management and the factors embraced by the Ergonomic Work Analysis, showing that the ergonomic methodology is able to go deeper in the scenarios of possible incident causes. This deepening enables the establishment of a relationship between the work context and the upcoming damage to the physical integrity of the worker. It acts as a complementary instrument in the traditional approach to the risk management. In order to explain the application of this methodology in a preventive way, it is presented a case study of a coal mill inspector in a siderurgic company. PMID- 22317220 TI - Cognition and asynchronous distribution between human and machine building accidents. AB - The creation of meaning in communication is a trading activity, resulting from the construction that is born of the interaction between subjects. That is, the meaning is not inherent to the relationship between words, signs and symbols that arise from negotiating a necessary and unavoidable. As the concepts of sense as discrete and static representations imply a notion of classical computing and design of a cognitive system corresponding conceptions of meaning construction as located and shared among agents implies notions of different computing and cognition. Several efforts have been developed to meet these demands. Among them are the Connectionism (also known as neural networks. Records on aspects of mental health and stress of flight professionals are present in the official reports of the organs of investigation of aviation accidents worldwide since its inception. Problems related to health physical and mental health of pilots (fatigue, stress, physiological and psychosocial problems) account for 19% of causal factors in aircraft accidents. The training seems a paradox when we know that these professionals receive regular training, have high education and technical training of high level. However, problems arise related to the implementation of learning that can be influenced to reduce their cognitive capacity, making it in practice, relatively unable to exercise its functions effectively and safely. PMID- 22317221 TI - Parachuting harnesses comparative evaluation on energy distribution grids. AB - This research aims to make a comparative evaluation of three different parachuting harnesses to work at heights in the energy industry, from the electricians' point of view concerning these products under the optics of usability and ergonomic principles, and mainly justified by the high quantity of injuries at the energy industry due to high falls. According to its main target, this field research is classified as exploratory-descriptive transversal viewing study and, considering this perspective, the study was developed in four steps. Research results have enlightened the weakest spots and the potential improvement opportunities of these products, developed to assure safety of the work at heights to the energy industry, according to the opinion of the users. Still, results point that, regardless of the model, these devices have adapting issues to fulfill the electrical sector user's needs. PMID- 22317222 TI - How to evaluate the risks of work equipment and installations for health and safety? Research and activities of the German Committee for Plant Safety and consequences for regulation. AB - Work equipment and installations with a high risk for health and safety of employees should be paid a special attention. The German Product Safety Act, which is aimed to manufacturers or distributors in order to protect consumers, maintains a conclusive catalogue of these so-called "installations in need of monitoring" fixing the work equipment and installations for which such special inspections can be demanded. This catalogue has remained unchanged for decades and has been transformed nearly unmodified into the Plant Safety Ordinance. Currently, there is a discussion about this catalogue in Germany. A major point of concern is the definition and the significance of "especially" dangerous work equipment and installations. Two recent research projects are dealing with the problem how to define "especially". PMID- 22317223 TI - Human reliability in petrochemical industry: an action research. AB - This paper aims to identify conflicts and gaps between the operators' strategies and actions and the organizational managerial approach for human reliability. In order to achieve these goals, the research approach adopted encompasses literature review, mixing action research methodology and Ergonomic Workplace Analysis in field research. The result suggests that the studied company has a classical and mechanistic point of view focusing on error identification and building barriers through procedures, checklists and other prescription alternatives to improve performance in reliability area. However, it was evident the fundamental role of the worker as an agent of maintenance and construction of system reliability during the action research cycle. PMID- 22317224 TI - Effect of shoe type on descending a curb. AB - The aim of this study was to evaluate the effect of shoe type on the performance of women during curb descent. Performance during curb stepping may be explained by biomechanical research that has evaluated the kinematics of overground walking and stair ascent and descent. Studies have reported that women exhibit performance differences when wearing high heels, flip flops and sneakers during overground walking and stair ascent and descent. Thus, in addition to features of the curb, the type of shoe being worn may also affect performance. Although several studies have investigated curb stepping, no known studies have investigated the effects of different types of footwear on curb descent performance. This research was conducted in a real-world environment where participants wore three different types of shoes and performed a series of activities that involved curb stepping. The subjects were videotaped while descending a curb, allowing for observation of changes in gait parameters. Results of this study indicate that wearing high heels leads to performance differences as compared to wearing flip flops or sneakers. PMID- 22317225 TI - Fundamental study on relationship between human injury probability due to fall and the fall height. AB - Many fatal accidents due to falling from height have happen at construction sites in Japan. The purpose of this study is about to seek new prevention methods of fatal accidents due to falling. For the first step, this study was carried out to find out "cause of death" in labor accidents by using past statistics data and was analyzed it. For the second, Butt dropping tests were carried out to measure impact load and acceleration of human head and neck by using simplified human model. After that, relationship between the human injury probability and the fall height was discussed by comparing with experimental results and some impact tolerance values for human. From the results of this study, impact force might be able to head trauma involved not only skull fracture but also cervical spinal cord injury. These results suggest needs to explore new protection equipment for head and cervical injuries prevention. PMID- 22317226 TI - Measuring step geometry using the Nose-to-Nose method: validity and repeatability. AB - Precise measurement of stairway geometry is important in order to establish whether a stairway meets design goals, standards and codes. The Traditional method of measuring risers and runs (goings) does not measure the stairs in the way that codes define risers and runs, and does not measure the stairs in the way users experience them. The Nose-to-Nose method does. This study was conducted to determine the validity and repeatability of this method. Two researchers used this method to study the risers and runs on two separate stairways, one carpeted and the other not. Results demonstrated a high degree of validity and repeatability. PMID- 22317227 TI - Assessment of slip resistance under footwear materials, tread designs, floor contamination, and floor inclination conditions. AB - Slip and fall incidences are common in our daily lives. They are not only important environmental safety issues but also important occupational safety and health problems. The purpose of this study was to use the Brungraber Mark II to measure the friction so as to investigate the effects of the shoe sole, surface condition and the inclined angle of the floor and their interactions on friction coefficient. The results of the study showed the effects of all the main factors and their interactions were significant (p<0.001). Engineering designs & ergonomic interventions in slip & fall prevention should take these factors in full consideration. PMID- 22317228 TI - Effect of walking surface perturbation training on slip propensity and local dynamic stability. AB - The objective of the current study was to evaluate the effect of walkway perturbation training on human dynamic walking stability and slip propensity. A new walkway perturbation training program was developed using an instrumented, split-belt treadmill. Walkway surface perturbation was composed of multiple, randomized perturbation pulses. Each pulse was created by sudden accelerating the treadmill belt underneath the dominant foot briefly. Five healthy older adults were involved in a laboratory study. An inertial measurement unit was attached to the subject's low back region to record 3D acceleration. Maximum Lyapunov exponent (maxLE) and transitional acceleration of whole body center of mass (TA_COM) were computed to quantify the local dynamic stability and slip propensity, respectively. The results indicated a significant training effect on both maxLE and TA_COM. It was concluded that the walkway perturbation training program significantly improved local dynamic stability and reduced slip propensity. PMID- 22317229 TI - The development of a universal approach to testing of walkway slip resistance in the U.S. AB - The measurement of walkway slip resistance is required to assess the risk of slipping. Unlike other countries, the U.S. has not decided upon a single approach to the measurement of slip resistance. Several types of tribometers are available to measure slip resistance however, the measured value of the slip resistance of a given surface has been found to be tribometer specific. The introduction of ASTM International Standard F2508 Standard Practice for Validation and Calibration of Walkway Tribometers Using Reference Surfaces, has produced a method which allows validation of each type of tribometer and the values generated during testing. PMID- 22317230 TI - Stair safety: bottom of flight illusion. AB - Falls near the bottom of a flight of stairs have resulted from an illusion that the person was stepping off onto the bottom landing when the person was still two treads or more above the landing. The illusion is caused by poor lighting and design defects built into the stairway. The poor lighting may be attributed to a building code that allows inadequate lighting near the bottom of external stairs in private residences. The design defect of truncating handrails before they reach the bottom tread may be due to confusion between "guards" and "handrails" and this confusion also appears to be promulgated by building code. PMID- 22317231 TI - The stochastic distribution of available coefficient of friction on quarry tiles for human locomotion. AB - The available coefficient of friction (ACOF) for human locomotion is the maximum coefficient of friction that can be supported without a slip at the shoe and floor interface. A statistical model was introduced to estimate the probability of slip by comparing the ACOF with the required coefficient of friction, assuming that both coefficients have stochastic distributions. This paper presents an investigation of the stochastic distributions of the ACOF of quarry tiles under dry, water and glycerol conditions. One hundred friction measurements were performed on a walkway under the surface conditions of dry, water and 45% glycerol concentration. The Kolmogorov-Smirnov goodness-of-fit test was used to determine if the distribution of the ACOF was a good fit with the normal, log normal and Weibull distributions. The results indicated that the ACOF appears to fit the normal and log-normal distributions better than the Weibull distribution for the water and glycerol conditions. However, no match was found between the distribution of ACOF under the dry condition and any of the three continuous distributions evaluated. Based on limited data, a normal distribution might be more appropriate due to its simplicity, practicality and familiarity among the three distributions evaluated. PMID- 22317232 TI - Review of walking hazards for railroad workers. AB - This is a review of walking tasks in the railroad environment, and the injuries that result from slips, trips, falls, or other acute or even non-traumatic exposures. The lack of federal regulations for railroad walkways has led several states to develop and enforce their own regulations. Support from the research literature for such regulations has come from biomechanical studies of the effects of walking on railroad ballast, which will be reviewed. PMID- 22317233 TI - Applying research to practice: generalist and specialist (visual ergonomics) consultancy. AB - Ergonomics is a holistic discipline encompassing a wide range of special interest groups. The role of an ergonomics consultant is to provide integrated solutions to improve comfort, safety and productivity. In Australia, there are two types of consultants--generalists and specialists. Both have training in ergonomics but specialist knowledge may be the result of previous education or work experience. This paper presents three projects illustrating generalist and specialist (visual ergonomics) consultancy: development of a vision screening protocol, solving visual discomfort in an office environment and solving postural discomfort in heavy industry. These case studies demonstrate how multiple ergonomics consultants may work together to solve ergonomics problems. It also describes some of the challenges for consultants, for those engaging their services and for the ergonomics profession, e.g. recognizing the boundaries of expertise, sharing information with business competitors, the costs-benefits of engaging multiple consultants and the risk of fragmentation of ergonomics knowledge and solutions. Since ergonomics problems are often multifaceted, ergonomics consultants should have a solid grounding in all domains of ergonomics, even if they ultimately only practice in one specialty or domain. This will benefit the profession and ensure that ergonomics remains a holistic discipline. PMID- 22317234 TI - Temporal aspects of increases in eye-neck activation levels during visually deficient near work. AB - In an experimental study two levels of oculomotor load were induced via optical trial lenses. Trapezius muscle activity was measured with bipolar surface electromyography and normalized to a submaximal contraction. Sixty-six subjects with a median age of 36 (range 19-47, std 8) viewed a black and white Gabor grating (5 c/deg) for two 7-min periods monocularly through a 0 D lens or binocularly through -3.5 D lenses. The effect of time was separately regressed to EMG in two different subgroups of responders: a High-Oculomotor-Load (HOL) and a Low-Oculomotor-Load (LOL) group. A linear regression model was fitted on group level with exposure time on the x-axis and normalized trapezius muscle EMG (%RVE) on the y-axis. The slope coefficient was significantly positive in the -D blur condition for only the HOL subgroup of responders: 0.926 + Time(min 1-7) * 0.088 (p = 0.002, r(2)=0.865). There was no obvious sign of this activity to level off or to stabilize. These results suggest that professional information technology users that are exposed to a high level of oculomotor load, during extended times, are at an increased risk of exhibiting an increased trap.m. activity. PMID- 22317235 TI - Lighting old age--how lighting impacts the ability to grow old in own housing, part one. AB - A functionally optimized housing development designed to meet the demands in different phases of living (universal design) may result in the elderly living longer in their own homes. In this study a total of 165 healthy persons were included out of a total of approximately 320 persons turning 75 years of age in 2009 living in Drammen municipality. They went through a quantitative, questionnaire-based interview (including VAS and SF-36) and 20 participants were then selected for a qualitative in depth interview. The lighting conditions in the kitchen, living room, bathroom, bedroom and staircase were measured according to a simplified procedure. The overall lighting conditions were evaluated to be rather low, with means between 35 and 121 Lux, but the quantitative interviews showed that on most questions the scores were rather low, indicating that the overall thriving is good regardless of rather low lighting values. PMID- 22317236 TI - Eye- and neck/shoulder-discomfort during visually demanding experimental near work. AB - Frequent use of digital information technology has an impact on eye- and neck/shoulder-discomfort. Studies with cross sectional and intervention design indicate an association between the two symptom categories. Still, whether visually demanding near work, per se, contributes to increased neck/shoulder discomfort remains a question of debate. The aim of this laboratory study was to assess if visually demanding experimental near work affects eye- and neck/shoulder-discomfort when the posture was adjusted for comfort and no movements were allowed. Thirty-three healthy subjects performed a visually demanding computer screen task (viewing task) under four different optical lens conditions: binocular -3.5 D and monocular -3.5 D, +3.5 D and +/- 0 D. During the experiment subjects were seated in an office chair (with neck support) that was individually adjusted for comfort. At baseline and after each viewing task, subjects reported their perceived eye- and neck/shoulder discomfort on Borg's CR 10 scale. Results show a significant increase of eye discomfort between baseline and the first viewing task, and a significant increase in neck/shoulder discomfort from baseline throughout the first three viewing tasks. Further analysis is required to determent whether the neck/shoulder discomfort was induced by the demanding near work or the static posture, or a combination. PMID- 22317237 TI - Co-variation in time between near-far accommodation of the lens and trapezius muscle activity. AB - Visual strain and discomfort may contribute to the generation of work-related musculoskeletal disorders among e.g. computer workers. A positive correlation on a group level between eye-lens accommodation and trapezius muscle activity has been reported. In this study we investigated the possibility of a direct, fast, connection between lens accommodation and trapezius muscles activity. The subjects focused alternately on Near and Far targets, with a mean switch time of 5 s, through four different lenses. The cross-correlation, R(tau) was computed, between the time signals of accommodation and electromyography (EMG) from 23 subjects. In the overall mean R(tau) of 736 curves, a small but significant correlation peak (0.019) with a delay (of the EMG signal) of about 0.3 s, revealed a small common component in the two signals. Among the lenses, the positive lens (3.5 D), showed the highest correlation peak (0.040). The correlation may be caused by a direct "hard-wired" connection between the ciliary and trapezius muscles. But it could also be caused indirectly by the subject's need for a more stable head in a more demanding visual task. The latter is supported by the result that the correlation was the highest in the positive lens condition. The present correlation is however weak and it has probably a low practical importance. PMID- 22317238 TI - Graphic and cultural aspects of pictograms: an information ergonomics viewpoint. AB - The use of pictograms is discussed considering their information content, graphic complexity and cultural dimension. The resemblance and the illusion theories are highlighted to define pictogram as a salience-based representation system, which communicational efficacy depends upon historical and cultural aspects in their interpretation. Thus, the competence in interpreting pictograms is considered relative to users' acquaintance with the pictorial system and with the referents. Pictogram as a general/neutral visual statement is questioned, pointing out the cultural and gender attributes added to pictures to represent people, professions and social events. As a result of this discussion, some critical points of the standardization of pictograms are presented. PMID- 22317239 TI - A study of subjective visual disturbances in jewellery manufacturing. AB - Subjective Visual Disturbances are silent adversaries that appear over a period of continued exposure and arise when the visual demands of the tasks exceed the visual abilities of the user. Jewellery manufacturing activity involves precision designs, setting the metal and stones, polishing and filing which requires higher visual demand. Therefore, it is expected that the jewellery manufacturing workers may experience subjective visual disturbances. This study was taken up with the following objectives 1) To study the presence of subjective visual disturbances among jewellery manufacturing workers and compare the same with VDT operators 2) To study the effect of work exposures on subjective visual disturbances and 3) to ascertain whether subjective visual disturbances have any permanent vision related problems. The study was carried out on jewellery manufacturing workers, VDT operators and on graduate students. The symptoms of subjective visual disturbances were identified using a questionnaire developed by Sheedy (2003). Viewing distances were measured and visual angles were calculated. The eye check- ups were also carried out. The subjective visual disturbances were higher in jewellery manufacturing workers. The findings suggest that work exposure has an impact on the causation of subjective visual disturbances. No pathological conditions of the eyes were observed. PMID- 22317240 TI - Application of digital human modeling and simulation for vision analysis of pilots in a jet aircraft: a case study. AB - Ergonomic evaluation of visual demands becomes crucial for the operators/users when rapid decision making is needed under extreme time constraint like navigation task of jet aircraft. Research reported here comprises ergonomic evaluation of pilot's vision in a jet aircraft in virtual environment to demonstrate how vision analysis tools of digital human modeling software can be used effectively for such study. Three (03) dynamic digital pilot models, representative of smallest, average and largest Indian pilot population were generated from anthropometric database and interfaced with digital prototype of the cockpit in Jack software for analysis of vision within and outside the cockpit. Vision analysis tools like view cones, eye view windows, blind spot area, obscuration zone, reflection zone etc. were employed during evaluation of visual fields. Vision analysis tool was also used for studying kinematic changes of pilot's body joints during simulated gazing activity. From present study, it can be concluded that vision analysis tool of digital human modeling software was found very effective in evaluation of position and alignment of different displays and controls in the workstation based upon their priorities within the visual fields and anthropometry of the targeted users, long before the development of its physical prototype. PMID- 22317241 TI - Operative strategies of HLB's scouts of a citrus property within the State of Sao Paulo, Brazil. AB - This research aimed to study the activity of the HLB's scouts, workers whose function is to identify symptomatic plants, in order to understand the physical constraints, cognitive and organizational involved in accomplishing the task, characterizing the operative approach used to identify diseased plants, and to elucidate what aspects hinder the identification of symptoms. The method adopted for the research was the Ergonomic Analysis of Work--EAW [6]. The results, after validation with the operators and management, allowed understanding the complex relationships between the physical, cognitive and organizational aspects present on activity. Major difficulties were observed mainly in relation to the disposal of the scouts on the platforms and in relation to working hours, at the beginning and end of the journey. Important findings have highlighted strategies, unknown by the organization, used by scouts to locate candidates' trees to the fine analysis of investigation of symptoms. In conclusion, the analysis enable to understand the constraints and find technical and organizational solutions to the survey work on citrus groves as well as it showed signs and symptoms not investigated yet or rarely considered by researchers involved on searches aimed at increasing the ability to diagnose the disease in the field. PMID- 22317242 TI - Ergonomic analysis of safety signs: a focus of informational and cultural ergonomics. AB - This paper presents the results of a research carried out in the states of Pernambuco and Rio Grande do Sul, Brazil about differences and similarities in the graphic representation of safety signs at factories of food, steel, shoes and construction/ building industries, together with their workers' opinions on the security signs. The overall results show differences in the sign structure across the states, confirming the influence of cultural differences on the design of safety signs, which must be taken into account during the design process. PMID- 22317243 TI - Visual ergonomics interventions in mail sorting facilities. AB - This study was performed between 2004 and 2011 at mail sorting facilities in Sweden. During this time, different interventions were performed. The first was a lighting intervention that had a positive impact on the postal workers, especially those with eyestrain. A new lighting system also improved the illuminance and gave better light distribution. The second intervention involved new personal spectacles for the postal workers who needed them and this had a positive effect on eyestrain. The third intervention involved a specific type of sorting spectacles for the postal workers who already used progressive lenses privately. The reading distances that the postal workers had while sorting the mail was inverted to the distances in their regular progressive lenses. The new sorting spectacles had a positive effect on head postures and on muscular activity. PMID- 22317244 TI - Point Navigation Map method to track low-income mobile user's interaction. AB - Mobile phones obtained large popularization in Brazil thanks to pre-paid (pay as you go) contracts. This kind of contract represents 82% of mobile phone connections in Brazil, corresponding to 143 million in a total of 174 million mobile phone accesses in the country. In this scenario, a research about the usability of mobile phones with 17 to 24 year old youngsters, living in poor communities, enrolled in the NGO Spectaculu. Usability tests were carried through with 30 youngsters from a NGO in Rio de Janeiro. Was made a extraction of the navigation sequence with data information of input and output from the system. Point Navigation Map was created to track low-income mobile user's interaction. PMID- 22317245 TI - Dosvox Usability: recommendations for improving interaction of blind people with the web using the system. AB - At present, it is recognized that the Internet plays key role in universalization of opportunities in society in which we live. For people with disabilities, the content must be accessible in all websites, but the assistive technologies used must be adequate to the specific needs of people with disabilities. Dosvox is a free system developed in the Universidade Federal do Rio de Janeiro (UFRJ) specially designed for blind people and used by them in the performance of their tasks with the use of computers. Previously, through exploratory research based on the observation of the interaction of blind students with the Web, usability problems were identified in the Dosvox interface and in the Webvox, the Web browser included in the system, and these problems were related to the fact that the interface is designed in accordance with the mental model of these Information Technology professionals. This study consolidate the problems in earlier phases of the research, link the results with usability heuristics of Nielsen and propose several improvements to Dosvox and its development process. PMID- 22317246 TI - Cognitively automated assembly processes: a simulation based evaluation of performance. AB - The numerical control of an experimental assembly cell with two robots--termed a cognitive control unit (CCU)--is able to simulate human information processing at a rule-based level of cognitive control. To enable the CCU to work on a large range of assembly tasks expected of a human operator, the cognitive architecture SOAR is used. The CCU can plan assembly processes autonomously and react to ad hoc changes in assembly sequences effectively. Extensive simulation studies have shown that cognitive automation based on SOAR is especially suitable for random parts supply, which reduces planning effort in logistics. Conversely, a disproportional increase in processing time was observed for deterministic parts supply, especially for assemblies containing large numbers of identical parts. In this contribution, the effect of phase-shifts in deterministic part supply is investigated for assemblies containing maximal different parts. It can be shown that the concept of cognitive automation is as well suitable for these planning problems. PMID- 22317247 TI - Usability and decision support systems in emergency management. AB - The actors in charge of an emergency response are confronted with severe difficulties in coordination and decision making, especially in major accidents. To facilitate coordination, various decision support systems (DSS) integrated in communication systems have been developed. However, many DSS in the rescue service organizations are afflicted with under-use and other usability problems. Drawing on both a literature review and an analysis of recently obtained survey data from rescue personnel concerning usability of common communication system in Swedish emergency organizations, this paper addresses the issue of usability of DSS. It is concluded that the impetus for developing DSS in many cases has been the technological possibilities per se, not taking the decision makers task structure and contextual factors into account. It is argued that priority should be given to functions that provide a visual overview of the event and facilitate storing of the series of decisions made during the response. PMID- 22317248 TI - State of the (net)work address Developing criteria for applying social networking to the work environment. AB - In an increasingly faster paced innovative world, maintaining the ability to innovate in spite of an aging work force will become every company's strongest leverage for success. Tapping the latent knowledge resources and creativity of overlooked employees and persisting crucial information for business conduct are promising results for social networking sites (SNS) in a working context. Usability and usefulness are exponential factors in creating a successful SNS. In order to make a SNS usable for a heterogeneous user group, analyses of user diversity in regard to social media need to be done. Furthermore differences in communication medium and frequency in regard to age, content, hierarchy position, departmental thresholds and company size need to be analyzed. For analysis purposes both qualitative and quantitative research methods were applied. Strong effects of age and communication content were found in survey with 194 participants. PMID- 22317249 TI - A method for work modeling at complex systems: towards applying information systems in family health care units. AB - Work in organizations requires a minimum level of consensus on the understanding of the practices performed. To adopt technological devices to support the activities in environments where work is complex, characterized by the interdependence among a large number of variables, understanding about how work is done not only takes an even greater importance, but also becomes a more difficult task. Therefore, this study aims to present a method for modeling of work in complex systems, which allows improving the knowledge about the way activities are performed where these activities do not simply happen by performing procedures. Uniting techniques of Cognitive Task Analysis with the concept of Work Process, this work seeks to provide a method capable of providing a detailed and accurate vision of how people perform their tasks, in order to apply information systems for supporting work in organizations. PMID- 22317250 TI - The influence of the modality of telecooperation on performance and workload. AB - Current industrial processes often involve the collaboration of people at distant and remote locations. The technological media for such a tele-cooperation reach from simple email or text-based chatting systems to highly-sophisticated systems for an interactive video-conferencing. But with limited bandwidth the communication between persons at distant locations is often restricted to single modalities. Although this may still be suitable for some tasks, it may result into serious shortcomings and decreased performance with complex tasks like cooperative assembly or maintenance. This is because restricted communication reduces the availability of a common ground, i.e. sharing a common understanding of knowledge, opinions, and goals. The study presented in this paper examines the effect of different communication media on performance of a collaborative assembly task. The results show that tele-cooperation leads to additional verbal communication (AM(direct)=71.1s; AM(video)=145.6s; AM(audio)=204.7s) and, thus, longer times to complete the task (AM (direct)=45.95 min; AM (video)= 50.2 min; am AM(audio)=56.16 min). The percentage of relative speech duration also increases significantly. Workload measurement with NASA-TLX did not show any significant differences between cooperation modes. The results allow estimating the effect of reduced communication modalities on time to complete an assembly task. This facilitates a quantification of temporal requirements in time-critical maintenance and repair tasks. PMID- 22317251 TI - Use of graphical modality in a collaborative design distant setting. AB - In this paper, we present an original environment, the Distributed Collaborative Design Studio (DCDS) which allows multimodal real-time remote exchanges, and which aims at re-creating remotely the conditions of co-present meetings. This environment associates a videoconference tool (supporting verbal and non-verbal communication) and an original realtime shared digital hand-drawn sketches system (supporting graphical communication). The users can import documents and annotate them in real-time at distance. In this paper, we are interested in studying the use of the graphical modality (digital sketch and document annotations) as a tool for collective design and remote communication. This study takes place in the framework of a collaborative architectural design studio, which has taken place during 3 month, and gathering students from Belgium and France to work together in 3 small groups mainly at distance. The study focuses on the role of graphical modality in the synchronous remote meetings supported by the DCDS. We identify the types of digital annotations made on the imported document, thanks to the electronic pen, and their role in the cognitive processes of designing and in the collaboration and communication processes. We also identify the different practices of digital sketching, according to the group and its collaborative strategies. We discuss the utility of the graphical modality as an efficient support for collaborative synchronous activities and show that the DCDS environment supports different strategies of collaborative design (co-design and distributed design). We conclude on recommendations for improving the system and for designing sketch-based collaborative environments. PMID- 22317252 TI - Invisible computer for collaborative design: evaluation of a multimodal sketch based environment. AB - In the areas of design, especially in architectural design, collaboration has become an important challenge. The specialization of skills increase, work teams are more and more extensive and the geographic distance between them increases too. The economic and ecological stakes related to remote collaboration are an evidence. This context involves the need to support most efficiently possible remote working meetings. We present the Distributed Collaborative Digital Studio (DSDC), a tool designed to recreate, in distant situations, the context of copresence meetings. This shared environment is created in the "invisible computer" approach [11]. The idea is that the tool should disappear from user's consciousness. Indeed, creative design activities require some fluidity in their process. Therefore, any involuntary interruption created by the system can potentially brake creativity. In this perspective, we investigate specifically the "invisibility" of our environment. To do this, we propose a framework for the operationalization of the concept and a methodology to test the system invisibility. This methodology was applied through a case study consisting of a corpus of 12 hours of remote collaborative design sessions with the DSDC. We highlight the learning effects while using our system, conclude on its effectiveness and discuss our methodology. PMID- 22317253 TI - Visual social network analysis: effective approach to model complex human social, behaviour & culture. AB - The advent and adoption of internet-based social networking has significantly altered our daily lives. The educational community has taken notice of the positive aspects of social networking such as creation of blogs and to support groups of system designers going through the same challenges and difficulties. This paper introduces a social networking framework for collaborative education, design and modeling of the next generation of smarter products and services. Human behaviour modeling in social networking application aims to ensure that human considerations for learners and designers have a prominent place in the integrated design and development of sustainable, smarter products throughout the total system lifecycle. Social networks blend self-directed learning and prescribed, existing information. The self-directed element creates interest within a learner and the ability to access existing information facilitates its transfer, and eventual retention of knowledge acquired. PMID- 22317254 TI - Online epistemic communities: theoretical and methodological directions for understanding knowledge co-elaboration in new digital spaces. AB - This paper presents, illustrates and discusses a generic framework for studying knowledge co-elaboration in online epistemic communities ("OECs"). Our approach is characterised by: considering knowledge co-elaboration as a design activity; distinguishing discussion and production spaces in OECs; characterising participation via the notion of role; fine-grained analyses of meaning, content and communicative functions in interactions. On this basis, three key issues for ergonomics research on OECs are discussed and illustrated by results from our previous studies on OSS and Wikipedia. One issue concerns the interrelation between design (task) and regulation. Whereas design task-oriented activity is distributed among participants, we illustrate that OCEs function with specialised emerging roles of group regulation. However, the task-oriented activity also functions at an interpersonal level, as an interplay of knowledge-based discussion with negotiation of competencies. Another issue concerns the foci of activity on the (designed) knowledge object. Based on a generic task model, we illustrate asymmetry and distinctiveness in tasks' foci of participants. The last issue concerns how design-use mediation is ensured by specific forms of mediation roles in OECs. Finally we discuss the degree of generality of our framework and draw some perspectives for extending our framework to other OECs. PMID- 22317255 TI - Design recommendations for the creation of icons for the elderly. AB - During employment of icons in order to represent system functions, specific user requirements from elderly people have not been scientifically gathered and thus will merely be considered during the process of system design. The survey, with explicit consideration of technology acceptance and experience of 120 elderly probands, looked into the comprehension of four different classes of non-animated graphical representations. It was shown that among elderly, the use of photos compared to pictograms or clip art leads to a significantly higher recognition rate. The mapping of actions rather than objects leads to a further reduction of the error probability and is thus, especially in the context of telemedicine, preferable for the target group. PMID- 22317256 TI - Bivariate pointing movements on large touch screens: investigating the validity of a refined Fitts' Law. AB - On the basis of three empirical studies Fitts' Law was refined for bivariate pointing tasks on large touch screens. In the first study different target width parameters were investigated. The second study considered the effect of the motion angle. Based on the results of the two studies a refined model for movement time in human-computer interaction was formulated. A third study, which is described here in detail, concerns the validation of the refined model. For the validation study 20 subjects had to execute a bivariate pointing task on a large touch screen. In the experimental task 250 rectangular target objects were displayed at a randomly chosen position on the screen covering a broad range of ID values (ID= [1.01; 4.88]). Compared to existing refinements of Fitts' Law, the new model shows highest predictive validity. A promising field of application of the model is the ergonomic design and evaluation of project management software. By using the refined model, software designers can calculate a priori the appropriate angular position and the size of buttons, menus or icons. PMID- 22317257 TI - How can multimodality be used to design usable interfaces in IPS2 for older employees? AB - Main objective of the recently started collaborative research project SFB/TR29 B4 is to provide cross-generational assistance to human operators working in industrial product-service systems (IPS(2)). By combining the ideas of action specificity and multimodality a more immediate and purposeful reaction towards warnings is assumed. For this purpose, an action-specific warning system in form of a glove has been developed. It provides either visual, auditory or haptic feedback or a combination of all modalities. In a first study this prototype was compared with a conventional warning system, where multimodal devices were directly mounted to the machine. The test scenario used in this study is the 'changing of a spindle' on a replica of a micro milling machine. It was conducted with 42 participants. The experimental design is a within-design in terms of the two warning systems and a between-design concerning the three modalities and its combinations. Results of the two-way ANOVA with repeated measures on both factors 'system' and 'modality' show a significant main effect for the 'modality' and a significant interaction effect between both factors. Especially the haptic warnings on the action-specific glove were described as "that kind of warning, which evokes the fastest response". PMID- 22317258 TI - Computer acceptance of older adults. AB - Even though computers play a massive role in everyday life of modern societies, older adults, and especially older women, are less likely to use a computer, and they perform fewer activities on it than younger adults. To get a better understanding of the factors affecting older adults' intention towards and usage of computers, the Unified Theory of Acceptance and Usage of Technology (UTAUT) was applied as part of a more extensive study with 52 users and non-users of computers, ranging in age from 50 to 90 years. The model covers various aspects of computer usage in old age via four key constructs, namely performance expectancy, effort expectancy, social influences, and facilitating conditions, as well as the variables gender, age, experience, and voluntariness it. Interestingly, next to performance expectancy, facilitating conditions showed the strongest correlation with use as well as with intention. Effort expectancy showed no significant correlation with the intention of older adults to use a computer. PMID- 22317259 TI - Training users to counteract phishing. AB - Phishing is an increasingly more prevalent form of online, social engineered scams that escalate costs and risks to society year to year. This study demonstrates an association between anti-phishing training techniques used in previous research and individual differences which could affect phishing susceptibility. Results indicated that anti-phishing training in both a simple comic and more complex video game form is helpful in decreasing phishing susceptibility as measured by Miss rates for all individuals including college aged and computer savvy participants. Based on the results of the present study, implications for future efforts to combat phishing are discussed. PMID- 22317260 TI - Effects of screen filter on visibility of alphanumeric presentation on CRT and LCD monitors. AB - In this paper, a research that deals with the problem of determining of the visibility of the alphanumeric presentation on CRT and LCD screens is presented, in conditions when the screen filters are used, and when they are not used. A methodology that can be used for determination of the visibility of alphanumeric symbols on VDT screens is presented. It is determined the existence of differences in visibility of alphanumeric presentations when screen filters are used, compared to conditions when they are not used. This difference was statistically significant, while the visibility of the presented alphanumeric symbols on CRT and LCD screens that use screen filters is lower than when they are not used. For this reason, the use of protective screen filter is recommended in circumstances where a very high level of glare exists, when the visual fatigue is common appearance and when a user performs a task that does not depend on the detection of stimuli whose RGB values are low. PMID- 22317261 TI - Incidence and risk factors for symptoms from the eyes among professional computer users. AB - Personal computers are used by a majority of the working population in their professions. Little is known about risk-factors for incident symptoms from the eyes among professional computer users. The aim was to study the incidence and risk-factors for symptoms from the eyes among professional computer users.This study is a part of a comprehensive prospective follow-up study of factors associated with the incidence of symptoms among professional computer users. 1531 computer users of different professions at 46 companies were invited, whereof 1283 answered a baseline questionnaire (498 men; 785 women) and 1246 at least one of 10 monthly follow-up questionnaires. The computer work-station and equipment were generally of a good standard. The majority used CRT displays.During the follow-up period 329 subjects reported eye symptoms. The overall incidence rate in the whole study group was 0.38 per person-year, 0.23 in the subgroup of subjects who were symptom free at baseline and 1.06 among subjects who reported eye symptoms at baseline. In the bivariate analyses significant associations were found with all explanatory variables, except BMI. The reduced multivariate model showed significant associations with extended computer work, visual discomfort (dose-response), eye symptoms at baseline (higher risk), sex (women=higher risk) and nicotine use.The incidence of eye problems among professional computer users is high and related to both individual and work-related factors. PMID- 22317262 TI - VDU workstations and vision in post office and bank operators. AB - A cross-sectional study was carried out on a sample of 26 VDU operators in a post office and a bank, working regularly on video display units. The study aimed at (1) determining the physical working conditions, particularly lighting conditions, (2) assessing employees' complaints, (3) measuring visual defects among operators in VDU workstations. The following results are revealed: (a) ergonomic shortcomings in workplace and work station design were clearly noticed (b) noise level was between 60 db and 78 db, (c) illumination parameters did not much the task and caused ocular symptoms and visual fatigue, (d) visual tests revealed vision defects in 84.6% of the cases, (e) visual fatigue was noticed at the end of the working day. The abnormal frequency of operators' complaints can be explained by the association of visual defects and inadequate working conditions. PMID- 22317263 TI - Risk factors for computer visual syndrome (CVS) among operators of two call centers in Sao Paulo, Brazil. AB - The aims of this study were to investigate work conditions, to estimate the prevalence and to describe risk factors associated with Computer Vision Syndrome among two call centers' operators in Sao Paulo (n = 476). The methods include a quantitative cross-sectional observational study and an ergonomic work analysis, using work observation, interviews and questionnaires. The case definition was the presence of one or more specific ocular symptoms answered as always, often or sometimes. The multiple logistic regression model, were created using the stepwise forward likelihood method and remained the variables with levels below 5% (p < 0.05). The operators were mainly female and young (from 15 to 24 years old). The call center was opened 24 hours and the operators weekly hours were 36 hours with break time from 21 to 35 minutes per day. The symptoms reported were eye fatigue (73.9%), "weight" in the eyes (68.2%), "burning" eyes (54.6%), tearing (43.9%) and weakening of vision (43.5%). The prevalence of Computer Vision Syndrome was 54.6%. Associations verified were: being female (OR 2.6, 95% CI 1.6 to 4.1), lack of recognition at work (OR 1.4, 95% CI 1.1 to 1.8), organization of work in call center (OR 1.4, 95% CI 1.1 to 1.7) and high demand at work (OR 1.1, 95% CI 1.0 to 1.3). The organization and psychosocial factors at work should be included in prevention programs of visual syndrome among call centers' operators. PMID- 22317264 TI - Visual challenges using Visual Display Units (VDU) in office landscapes. AB - A total of 85 VDU operators, in three main Scandinavian Alcatel-Lucent headquarters, were followed in a process moving from single occupancy offices to an office landscape. This paper discusses the visual challenges and implications in such a transfer. In the oral presentation recommendation on how to avoid visual problems will be given. PMID- 22317265 TI - Visual ergonomics and computer work--is it all about computer glasses? AB - The Swedish Provisions on Work with Display Screen Equipment and the EU Directive on the minimum safety and health requirements for work with display screen equipment cover several important visual ergonomics aspects. But a review of cases and questions to the Swedish Work Environment Authority clearly shows that most attention is given to the demands for eyesight tests and special computer glasses. Other important visual ergonomics factors are at risk of being neglected. Today computers are used everywhere, both at work and at home. Computers can be laptops, PDA's, tablet computers, smart phones, etc. The demands on eyesight tests and computer glasses still apply but the visual demands and the visual ergonomics conditions are quite different compared to the use of a stationary computer. Based on this review, we raise the question if the demand on the employer to provide the employees with computer glasses is outdated. PMID- 22317266 TI - Training time estimation to improve alarm reactions. AB - Prior researchers have demonstrated that training may be an effective strategy for improving operator reactions to alarm systems with less than perfect reliability. Of the training strategies tested, recognition of temporal patterns in prior sensor activations seems to offer the greatest promise for improving the speed and appropriateness of subsequent alarm reactions. The current research was completed to clarify which of three temporal interval training methods leads to the most appropriate alarm reactions. Fifty-six undergraduates evaluated whether alarms occurring after sensor activations were true or false, based on elapsed time between the sensor signals and the alarm signals. Participants completed five training sessions to learn to estimate time intervals using simple repetition training, performance feedback, or performance feedback plus subdivision cues. Contrary to expectations, results indicated that participants did not benefit differentially from temporal interval training. Differences between pre- and posttest interval estimation performance was similar among groups, and training groups performed comparably when reacting to signals. Participants generally focused on advertised alarm system reliability, responding more appropriately and more quickly to lower reliability alarms. Future researchers and designers should replicate these findings with realistic tasks and real-world complex task operators to determine their generalization. PMID- 22317267 TI - Multimodal urgency coding: auditory, visual, and tactile parameters and their impact on perceived urgency. AB - Through a series of investigations involving different levels of contextual fidelity we developed scales of perceived urgency for several dimensions of the auditory, visual, and tactile modalities. Psychophysical ratings of perceived urgency, annoyance, and acceptability as well as behavioral responses to signals in each modality were obtained and analyzed using Steven's Power Law to allow comparison across modalities. Obtained results and their implications for use as in-vehicle alerts and warnings are discussed. PMID- 22317268 TI - Selection of a voice for a speech signal for personalized warnings: the effect of speaker's gender and voice pitch. AB - There is an increasing interest in multimodal technology-based warnings, namely those conveying speech-warning statements. This type of warning may be tailored to the situation as well as to the target user's characteristics. However, more information is needed on how to design these warnings in a way that ensures intelligibility, promotes compliance and reduces the potential for annoyance. In this context, this paper reports an exploratory study whose main purpose was to assist the selection of a synthesized voice for a subsequent compliance study with personalized (i.e., using the person's name) technology-based warnings using Virtual Reality. Participants were requested to listen to speech signals, gathered from a speech synthesizer and post-processed in order to change the pitch perception, and then these were evaluated by fulfilling the MOS-X questionnaire. After that, the participants ranked the voices according to their preference. The effects of the speaker's gender and voice pitch, on both ratings and ranking were assessed. The preference of the male and female listeners for a talker's voice gender was also investigated. The results show that participants mostly prefer as first choice the high-pitched female voice, which also gathered the highest overall score in the MOS-X questionnaire. No significant influence of the participants' gender was found on the assessed measures. PMID- 22317269 TI - Auditory backup alarms: distance-at-first-detection via in-situ experimentation on alarm design and hearing protection effects. AB - The purpose of this study was to assess normal hearing listeners' performance in detecting a stationary backup alarm signal and to quantify the linear distance at detection point. METHOD: Detection distances for 12 participants with normal hearing were measured while they were fitted with 7 hearing protectors and while they were unoccluded (open ear). A standard (narrowband) backup alarm signal and a broadband (pulsed white noise) backup alarm signal from Brigade[1] were used. The method of limits, with distance as the physical measurement variable and threshold detection as the task, was employed to find at which distance the participant could first detect the backup alarms. RESULTS: A within-subject Analysis of Variance (ANOVA) revealed a significant main effect of the listening conditions on the detection distance in feet. Post hoc analyses indicated that the Bilsom L3HV conventional passive earmuff (at 1132.2 ft detection distance) was significantly poorer compared to all other HPDs and the open ear in detection distance achieved, and that there were no statistically-significant differences between the unoccluded ear (1652.3 ft), EB-15-Lo BlastPLGTM (1546.2 ft), EB-15-Hi BlastPLGTM (1543.4 ft), E-A-R/3M Combat ArmsTM earplug-nonlinear, level-dependent state (1507.8 ft), E-A-R/3M HiFiTM earplug (1497.7 ft), and Bilsom ImpactTM dichotic electronic earmuff (1567.2 ft). In addition, the E-A-R/3M Combat ArmsTM earplug-passive steady state resulted in significantly longer detection distances than only the open ear condition, at 1474.1 ft versus 1652.3 ft for the open ear. ANOVA also revealed a significant main effect of the backup alarm type on detection distance. The means were 1600.9 ft for the standard (narrowband) backup alarm signal, and a significantly closer 1379.4 ft was required for the Brigade broadband backup alarm signal. DISCUSSION: For on-ground workers, it is crucial to detect backup alarm signals as far away as possible rather than at close distances since this will provide them more time to react to approaching vehicles. The results of this study suggest that as the attenuation of the hearing protectors increases, precautions should be considered by safety professionals. This is because, as it was the case with the Bilsom passive earmuff and E-A-R/3M Combat ArmsTM earplug-passive steady state, high attenuation minimizes the detection distance and as a result on-foot workers will have less time to react to any approaching vehicle. The main effects of the type of backup alarm signal demonstrated a statistically-significant advantage of the standard backup alarm over the broadband backup alarm on detection distance in feet. The magnitude of the improvement produced by the standard backup alarm was 221.5 feet, a very large margin. For example, with a vehicle backing at 10 mph, the 221.5 ft decrease in detection distance with the Brigade alarm equates to the vehicle arriving 15 seconds sooner at the worker from the point at which its alarm was first heard. PMID- 22317270 TI - The impact of emotions and predominant emotion regulation technique on driving performance. AB - Emotion-provoking stimuli abound on modern roadways. Driving measures, of both longitudinal and lateral control of the vehicle, have been shown to vary based on affective influences. Research, however, has yet to address how drivers' individual techniques to mitigate emotional reactions influence driving performance. To address this issue, the present study featured a dual-task protocol involving simulated driving together with processing of emotionally valenced images with a focus on different Predominant Emotion Regulation Techniques (PERT): one adaptive strategy (task-focused coping) and one maladaptive style (emotion-focused coping). Dependent measures included mean driving speed and number of lane excursions. Results indicated that pleasant images degraded longitudinal control to the greatest extent, while unpleasant images produced the greatest detriment in lateral control. Additionally, individuals' PERT played a major interactive role in drivers' longitudinal control leading task-focused females and emotion-focused males to adhere more closely to the speed limit; yet, it did not affect their lateral control. Results hold important potential implications for the amount or variety of training necessary for driver licensure to promote and sustain safe vehicle control. PMID- 22317271 TI - Virtual reality based therapy for post operative rehabilitation of children with cerebral palsy. AB - Virtual reality is the use of interactive replication created with computer hardware and software to impart users with opportunities to engage in environments that appear to feel similar to real world objects and events. The commonest rehabilitation program of cerebral palsy children involves stretching, strengthening, mobilization and various other activities, whereas the use of virtual reality based training (VRBT) for rehabilitation of cerebral palsy is not common. To understand the effect of VRBT a study was formulated. Twenty nine subjects participated (study group--14 and control group--15). Outcome measures were MACS, PBS, level of participation, motivation, cooperation and satisfaction of the child. Results revealed that balance and manual ability were significantly improved in both the groups (Balance: study: t-2.28, p<0.05; control: t-3.5, p<0.01; Manual ability: study: t-5.58, p<0.001; control: t-7.06, p<0.001). PBS had significantly greater improvement in the study group (t-t-2.02, p<0.05). Level of participation, motivation, cooperation and satisfaction of the child were also reported to be significantly higher among the study group as compared with control group. To the author's best knowledge, this is the first study on using the VR-based therapy for the postoperative rehabilitation of children with CP which need further elaboration with larger sample size. PMID- 22317272 TI - Ratings checklist for warnings: a prototype tool to aid experts in the adequacy evaluation of proposed or existing warnings. AB - In the field of forensic human factors, experts are often called upon to assess and evaluate the adequacy of new or existing products' warnings or warnings systems. The usual goal of this evaluation is to arrive at a simple binary decision regarding the warning in question (i.e., does it "pass/fail", or is it "adequate/inadequate"). However, such a warning assessment process may in fact be quite complex and multidimensional in its execution. The existing warnings research literature has identified a fairly large number of warnings features or factors likely to have an impact on a given warning's effectiveness or adequacy. The tool addressed in this article is intended for use by a warnings expert (as opposed to one less knowledgeable and informed about complex warnings issues), and can serve as a reminder checklist to help ensure that the expert has taken into consideration the most relevant features or factors during such a warnings adequacy assessment. PMID- 22317273 TI - Tire aging: a human factors analysis of failure to warn and inform. AB - A scenario of an automotive accident caused by tire failure is given followed by a human factors analysis of the information available to consumers on tire aging. Consumers have not been told that the age of the tire is a safety concern. It is not easy to decode the date of manufacture on tires. More publicity and prominent warnings are needed to communicate the dangers of older tires. Also, better ways to present the date of manufacture so that consumers can more easily and accurately assess tire age are needed. PMID- 22317274 TI - Ride-on lawnmowers warnings: slope measurements and safety-by-separation. AB - Various single-rider open vehicles, such as lawnmowers, are susceptible to overturning on slopes that are too steep for them. Warnings have included separation from the vehicles and avoiding slopes that are too steep. A recommended maximum slope is commonly 15 degrees. However, many individuals cannot evaluate slopes just by sight. Some mower manufacturers have warned about too steep slopes and have provided slope gauges for users to determine the slopes in natural settings. This article evaluated the usefulness of such gauges for users who might be expected to need to evaluate slopes and the efficacy of a separation procedure for avoiding injuries. It was concluded that neither of these were likely to be successful and suggestions are made for alternative approaches. PMID- 22317275 TI - What should I do?--a study about conflicting and ambiguous warning messages. AB - Warnings are intended to reduce accidents caused by hazards. Behavioral compliance is the most important measure of warning effectiveness. However, in result of diverse circumstances (e.g., distraction, misuse, negligence), conflicting or ambiguous safety messages can be perceived. Since these are recurrent and can result in wrong behaviors encompassing severe consequences, such cases should be studied for safety purposes. We report findings on the participants' compliant behavior when performing a work-related task, while immersed in a virtual environment, and investigate the effect of conflicting messages on compliance with warnings. Two warnings (one regular and one with an appended out-of-order sign) and two types of signs (static and dynamic) were considered. The warning with the out-of-order sign configures the case of potentially conflicting messages. The gender effect was also investigated. The participants' behavior was assessed regarding to pushing a button as directed by the warnings. In the "out-of-order" warning, compliance was higher in the dynamic situation (53.3%) than in the static one (3.3%). Comparing with the non conflicting warning, compliance was higher for both situations (static: 76.7%; dynamic: 100%). Women complied more than men. Although these results have limitations in their generalization, they are nonetheless relevant and deserve to be studied further. PMID- 22317276 TI - Users/consumers differences regarding ergonomics and design theory and practice. AB - This paper presents the concept of direct and indirect users, a key issue to cooperation between ergonomists, designers and managers involved in a sustainable approach to design. What issues for Ergonomics and Design are launched by this concept? User/consumer differences should be approached taking into account Ergonomics and Design theory and practice. What dialogue and tools could help the ergonomist/designer/manager to respond to all the requirements of the future clients of the product? PMID- 22317277 TI - Ergonomics content in the physical education teacher's guide in Rwanda. AB - An important aspect that affects the effectiveness of ergonomic programs is that inefficient mechanical functioning start at an early age and that back pain and posture problems are already evident in children. Children, from a very early age, as well as adults spend an ever increasing amount of their time in front of computer and television screens. The cumulative effect of this sedentary lifestyle leads to improper posture, as well as inefficient and harmful movement patterns and loss of basic physical skills. Physical Education course should deal not only with sports and physical activities, but also with broader aspects of life-skills and physical functionality. It should offer a solution to the modern technology-based society. Keeping this in perspective, Ergonomics content was introduced in Physical Education Teacher's Guide in Rwandan schools with an aim in preventing musculoskeletal disorder in children. PMID- 22317278 TI - International English and ergonomics: a romance in the making? AB - This paper argues that it would be useful for ergonomists and experienced English Language Teaching (ELT) professionals to collaborate as this would be of substantial interest to both sets of professionals. The ongoing debate in ELT on International English (IE) might usefully help to guide ergonomists if and when they require to judge that English is used at appropriately high levels in the workplace in non-English speaking countries. It may also help ergonomists who are non-native speakers (NNSs) of English to gain greater access to the top specialist journals and to found new e-journals on Ergonomics in English that deserve international recognition. At the same time ELT specialists would have great interest in advising ergonomists on these matters, in part, as a means of testing current hypotheses on the tendencies for new varieties of English to develop and win acceptance both from native and non-native speakers of English as setting standards of communicative competence in English both for end users of English in their professional lives and for well-structured and clear written academic debate. PMID- 22317279 TI - Physical and postural aspects of teachers during work activity. AB - Studies indicate that teachers constitute a professional segment, in which the work characteristics and the demands originating from the act of teaching, favor the emergence of sickness, concerning physical or emotional aspects. The present work aimed to describe physical and postural aspects during the working activity of teachers. A total of 120 elementary school teachers (1st to 8th grade) took part in the survey. For data collection, a questionnaire was applied: it included personal and occupational information, perception of discomfort and being off work; physical strength activities; posture at work and physical conditioning activities. The average age of teachers of the present sample corresponds to 35,8 years. In relation to activities which generate more physical strength, the answer none of the activities was predominant with 30 answers; followed by writing on the board, standing up during the period of classes, explanation of the subjects, class elaboration, correction of homework and others. The area of the body with higher amount of occurrences and prevalent discomfort referred to the lower limbs and spinal cord. These data inform the necessity of investing in prevention programs for the teachers, in order to develop strategies into the organizational context and interventions at the work environment. PMID- 22317280 TI - The deaf and the classroom design: a contribution of the built environmental ergonomics for the accessibility. AB - In any concept of school design, classroom occupies the central place. Dimensions, lighting, the equipment needed, ventilation are old questions already answered, even in form of laws and standards adopted. However, the best use of available materials and physical conditions of comfort is not sufficient for a classroom design guaranteed success. The classroom should provide deaf students elements to facilitate the learning process, eliminating as much as possible the obstacles created by lack of hearing and allowing them to have the same access to learning as a listener student. As users of a school building, teachers, students, parents and staff are the best evaluators of the physical environment of schools. The environmental comfort is a largest ally of pedagogy. The learning comes from the perception and the concentration of students in the classroom. The purpose of this study is to detect the role of direct perception (physical) and indirect (intangible) elements that informs and have symbolic value, and propose layouts for accessible classrooms to deaf students. The ergonomics of the built environment evaluation methods could use the participatory design method tools as basis to assessing how users perceive and use the school environment. PMID- 22317281 TI - Cross-disciplinary problem-solving workshop: a pedagogical approach to anticipate ergonomist engineering design collaboration. AB - The aims of this paper are to present concept and results of an innovative educational model approach based on ergonomics involvement in industrial project. First we present Cross disciplinary Problem solving Workshop by answering three questions:1) What is a CPW: A partnership between Universities and one or several companies, purposes of it are first to increase health, well being, companies teams competencies, and competitiveness, second to train the "IPOD generation" to include risks prevention in design. 2) How does it work? CPW allows cooperation between experience and new insight through inductive methods. This model follows the Piaget (1) philosophy linking concrete world to abstraction by a learning system associating realization and abstraction. 3) Is it successful? In order to answer this third question we will show examples of studies and models performed during CPWs.It appears that the CPWs produce visible results in companies such as new process designs, new methods, and also changes in lectures. However some less visible results remain unclear: How the company personnel evolve during and after CPW? Does CPW motivate our future engineers enough to continuously improve their skills in risk prevention and innovative design? PMID- 22317282 TI - Integrating community ergonomics with educational ergonomics--designing community systems to support classroom learning. AB - This paper offers a conceptual framework, bolstered by empirical evidence, for two conclusions: (1) that variability in student learning is prominently influenced by ergonomic design features, not only of classrooms and school systems, but also of surrounding communities; and (2) a systems concept of learning environments therefore is required to support student learning, based on integrating educational with community ergonomics. Educational system design factors known to strongly influence student learning first are reviewed. One of the most prominent of these is the socioeconomic status of communities in which schools are housed. Independent lines of evidence then are introduced that may account for how and why community design affects learning. The paper closes with recommendations for persuading policymakers and educators that closer integration of school system operations and functions with those of the surrounding community, with a central goal of upgrading community design conditions, represents a highly promising opportunity for improving student learning performance. One major challenge is to heighten awareness that learning environments outside the classroom are as or more important as those inside, in terms of influencing not only test but broader educational and societal trajectories of children. PMID- 22317283 TI - Ergonomic analysis for elementary school teachers. Preliminary trial for elementary schools in the province of Buenos Aires. AB - This article presents the results of a preliminary trial, in the context of an intervention, developed by a team of ergonomists under the request of the Occupational Health Department of the General Management of Schools in the Province of Buenos Aires, Argentina. We present a reformulation of the request and the results obtained in 2009 from observations and interviews held in three schools in the province of Buenos Aires in which different jobs positions were assessed. From this stage onwards, the tools were validated and new aspects were shown, particularly in relation to the high variety of real situations in the education sector. PMID- 22317284 TI - Analysis of environmental factors affecting the quality of teacher's life of public schools from Umuarama. AB - In this study valued 100 public school teachers statewide Umuarama-Pr, through Maslach Burnout Inventory (MBI) and also a socio-demographic questionnaire with objective factors to analyze the work environment that affect the quality of life for teachers public schools in Umuarama. The results indicated that teachers age between 20 and 30 years show high index of emotional exhaustion. Between 30 and 40 years have a low average emotional exhaustion and depersonalization and an average professional achievement. Teachers between 40 and 50 years of aged had resulted in the average within the fields Burnout Inventory with a group that's worrying, because it is the limit in all items that characterize the burnout syndrome. Already in the professionals aged between 50 and 60 years have seen high levels of emotional exhaustion, low depersonalization and low professional achievement, this group, which probably already had some of these symptoms are only now been identified. This shows how is the quality of life of the group of teachers surveyed, and indicates the need for action to change this situation and find solutions. A suggestion of this work is to build a center for psychological support for teachers to learn to handle everyday situations. PMID- 22317285 TI - Ergonomics and education as a strategy for sustainable development in business. AB - It is part of the vocabulary of organizations, and the agendas discussed the subject of "Sustainability", but there are few companies that implement practices or even know the means of implementing sustainable practices. The objective of this paper is to discuss an approach to education for sustainable development (ESD) based on the concepts and practice of ergonomics, as a consequence of this approach allows the implementation of integration initiatives focused on sustainability, such as eg. energy efficiency and consumer awareness thus allowing a means of reducing costs and operating expenses, increased competitiveness and significant contributions to corporate sustainability. There is also the inclusion of sustainability in corporate strategic planning, and their implications in the different spheres of the market. PMID- 22317286 TI - Burnout syndrome, working conditions, and health: a reality among public high school teachers in Brazil. AB - The objective of the study was to evaluate the occurrence of Burnout Syndrome in 100 teachers of six public high schools and its correlation with working conditions in a southeast city of Brazil. Characterization of the sample occurred after application of a socio-demographic questionnaire. Evaluation of the working conditions was done by means of an Ergonomic Working Analysis. The presence of Burnout Syndrome was evaluated by means of the Maslach Burnout Inventory. The sample presented the predominance of women, with an average age of 40.4 and the majority married with children. Roughly 50% had less than 10 years of service, and more than half of the teachers taught more than 18 classes per week. Hoarseness after work was principally reported among women, which required many days off for health treatment. Environmental conditions reflect inadequacy in relation to noise, light, humidity and temperature. Presence of pain in the upper limbs was especially high among women. Risk of musculoskeletal disorders in the upper limbs predominated as moderately important to significant. We also identified an average distance walked by teachers of 1.5 Km and an average of 4.2 Kg of school supplies carried between classes. The Burnout Syndrome presented a high score for depersonalization principally among men, but it has association with both sexes. Emotional exhaustion correlates with noise, depersonalization, and personal fulfillment, in addition to the high number of weekly lessons. It can be concluded that Burnout syndrome is present among teachers, principally in terms of depersonalization, deserving the attention of government officials and the schools, as well as the teachers themselves. PMID- 22317287 TI - Irregular working times and metabolic disorders among truck drivers: a review. AB - A number of studies to better understand the complex physiological mechanism involved in regulating body weight have been conducted. More specifically, the hormones related to appetite, leptin and ghrelin, and their association to obesity have been a focus of investigation. Circadian patterns of these hormones are a new target of research. The behaviour of these hormones in individuals subject to atypical working times such as shiftwork remains unclear. Shiftwork is characterized by changes in biological rhythms and cumulative circadian phase changes, being associated with high rates of obesity and metabolic syndrome. Truck drivers, who work irregular shifts, frequently present a high prevalence of obesity, which might be associated with work-related factors and/or lifestyle. In this context, the aim of this paper was to discuss the relationship of body mass index, appetite-related hormones and sleep characteristics in truck drivers who work irregular shifts compared with day workers. PMID- 22317288 TI - Need for recovery from work and sleep-related complaints among nursing professionals. AB - The concept of need for recovery from work (NFR) was deduced from the effort recuperation model. In this model work produces costs in terms of effort during the working day. When there is enough time and possibilities to recuperate, a worker will arrive at the next working day with no residual symptoms of previous effort. NFR evaluates work characteristics such as psychosocial demands, professional work hours or schedules. However, sleep may be an important part of the recovery process. The aim of the study was to test the association between sleep-related complaints and NFR. A cross-sectional study was carried out at three hospitals. All females nursing professionals engaged in assistance to patients were invited to participate (N = 1,307). Participants answered a questionnaire that included four sleep-related complaints (insomnia, unsatisfactory sleep, sleepiness during work hours and insufficient sleep), work characteristics and NRF scale. Binomial logistic regression analysis showed that all sleep-related complaints are associated with a high need for recovery from work. Those who reported insufficient sleep showed a greater chance of high need for recovery; OR=2.730 (CI 95% 2.074 - 3.593). These results corroborate the hypothesis that sleep is an important aspect of the recovery process and, therefore, should be thoroughly investigated. PMID- 22317290 TI - Musculoskeletal reported symptoms among aircraft assembly workers: a multifactorial approach. AB - The aim of this study was to evaluate factors associated with reported work related musculoskeletal symptoms among aircraft assembly workers. Population consisted of 552 (491 men/61 women) workers who performed tasks related to the work of aircraft assembly. Participants completed a comprehensive questionnaire, including socio-demographic information, habits/lifestyles, working conditions, and work organization. Workers also answered the Nordic Musculoskeletal Questionnaire to obtain data on musculoskeletal symptoms. Multivariate logistic regression was performed to analyze factors associated with musculoskeletal reported symptoms. Results showed that body regions with the highest prevalence of reported musculoskeletal symptoms were similar when referred the past twelve months and the past seven days. Significant factors associated with musculoskeletal symptoms included variables related to conflicts at work, sleep problems, mental fatigue, and lack of time for personal care and recovery. Working time in the industry was associated only with reports for the last seven days and regular physical activity off-work seems to be a positive factor in preventing musculoskeletal symptoms for the past twelve months. The results highlight the multi-factorial nature of the problem. Actions to prevent musculoskeletal diseases at the aircraft assembly work should consider multiple interventions that would promote better recovery between work shifts. PMID- 22317289 TI - Morbidity among nursing personnel and its association with working conditions and work organization. AB - INTRODUCTION: Work organization patterns and working conditions experienced by nursing personnel in the hospital settings may be associated to increased morbidity among these health workers. AIM: To estimate the prevalence and factors associated with self-reported diseases among nursing personnel at the emergency hospital in Rio Branco/State of Acre, Brazil. METHODS: A cross-sectional study was conducted involving 272 participants who answered a questionnaire including sociodemographic characteristics, working conditions, lifestyles, work ability, and a fatigue perception scale. The self-reported diseases in the 12 months prior to data collection were considered the dependent variable. RESULTS: A total of 85.7% of the participants reported one or more diseases in the past 12 months. Most prevalent diseases were: musculoskeletal diseases (37.1%), digestive diseases (28.7%), mental disorders (28.3%), work injuries (27.9%), and respiratory diseases (26.8%). The following significant variables remained in the final model: high work demands (OR 2.69), reported fatigue (OR 3.59), night work (OR 6.55) and being a technician or nursing assistant (OR 4.23). CONCLUSIONS: Variables related to working conditions and work organization were associated with the occurrence of reported diseases among nursing professionals. Health promotion measures at work require a comprehensive approach including the working conditions and the work organization. PMID- 22317291 TI - Work ability among hospital food service professionals: multiple associated variables require comprehensive intervention. AB - The work of hospital food service is characterized by demands that can be associated with work ability--WA. The aim of this study was to evaluate factors associated with WA among hospital food service professionals and recommend intervention measures. This is a cross sectional study carried out in 2009, conducted in a hospital of Sao Paulo, Brazil. Participants were 76 (96.2%) of the eligible. They filled out a questionnaire including socio-demographic data, life styles, working conditions and WA. Multivariate linear regression analyses were performed. Factors associated with WA were age (p = 0.051), over commitment (p = 0.011), effort-reward ratio (p = 0.002) and work injuries (p < 0.001). In spite was a young population, age was associated with WA. Association with work injuries is consistent with the theoretical model that demonstrated that health status is the basis to maintain the WA. The association of effort-reward imbalance shows that issues related with work organization are relevant for these workers. The association of overcommittment suggests that workers recognize their responsibility with the therapeutic processes of patients. Results showed a number of features of different nature that should be taken into account when implementing measures to improve the WA, to be applied at different levels: individual, task and institutional. PMID- 22317292 TI - Relationship between construction workers' musculoskeletal disorders and occupational health service activities. AB - Construction work consists of numerous factors that influence workers' occupational health and that load the musculoskeletal system in particular. Musculoskeletal disorders are responsible for over a third of all sick leaves lasting over nine days in the construction industry. Occupational health services (OHS) were organized for 85% of the construction workers in our study. The proportion of construction workers who had suffered from chronic or repetitive neck and shoulder, shoulder or arm, or low-back disorders was 55.6%, 44.8% and 42.1%, respectively. Those who felt that they had received enough information, advice or guidance from OHS concerning work posture, work performance or work tools were more often those who had not suffered from shoulder or arm disorders (60.9% vs. 39.1%, p=.024, respectively) or low-back disorders (63.6% vs. 36.4%, p=.034, respectively) during the last month than those who had. Those who had received enough support from OHS concerning maintenance of work ability were more often workers who had not suffered from low-back disorders during the last month than those who had (63.3% vs. 36.7%, p=.004, respectively). OHS should focus more on workers who would really benefit from their activities at a particular time and in a particular situation (primary, secondary or tertiary prevention) and who are themselves devoted to improving their health. PMID- 22317293 TI - Flow diagram analysis of electrical fatalities in construction industry. AB - The current study reanalyzed 250 electrical fatalities in the construction industry from 1996 to 2002 into seven patterns based on source of electricity (power line, energized equipment, improperly installed or damaged equipment), direct contact or indirect contact through some source of injury (boom vehicle, metal bar or pipe, and other conductive material). Each fatality was coded in terms of age, company size, experience, performing tasks, source of injury, accident cause and hazard pattern. The Chi-square Automatic Interaction Detector (CHAID) was applied to the coded data of the fatal electrocution to find a subset of predictors that might derive meaningful classifications or accidents scenarios. A series of Flow Diagrams was constructed based on CHAID result to illustrate the flow of electricity travelling from electrical source to human body. Each of the flow diagrams can be directly linked with feasible prevention strategies by cutting the flow of electricity. PMID- 22317294 TI - Predicting long-term absenteeism from work in construction industry: a longitudinal study. AB - In this study we examine whether the Work Ability Index (WAI) has additional value in predicting long-term absenteeism in construction industry. Results of the study show that the WAI has additional value in predicting absenteeism, but that the amount of explained variance is low. This is partly due to the definition of absenteeism in The Netherlands, where this study took place. PMID- 22317295 TI - The evaluation of team lifting on physical work demands and workload in ironworkers. AB - Lifting and carrying heavy loads occur frequently among ironworkers and result in high prevalence and incidence rates of low back complaints, injuries and work disability. From a health perspective, little information is available on the effect of team lifting on work demands and workload. Therefore, the objective of this study was to compare the effects of team lifting of maximally 50 kg by two ironworkers (T50) with team lifting of maximally 100 kg by four ironworkers (T100). This study combined a field and laboratory study with the following outcome measures: duration and frequency of tasks and activities, energetic workload, perceived discomfort and maximal compression forces (Fc peak) on the low back. The physical work demands and workload of an individual iron worker during manual handling of rebar materials of 100 kg with four workers did not differ from the manual handling of rebar materials of 50 kg with two workers, with the exception of low back discomfort and Fc peak. The biomechanical workload of the low back exceeded for both T50 and T100 the NIOSH threshold limit of 3400N. Therefore, mechanical transport or other effective design solutions should be considered to reduce the biomechanical workload of the low back and the accompanying health risks among iron workers. PMID- 22317296 TI - Assessment method of accessibility conditions: how to make public buildings accessible? AB - The enforcement of accessibility today has faced several difficulties, such as intervention in historic buildings that now house public services and cultural activities, such as town halls, museums and theaters and should allow access, on equal terms to all people. The paper presents the application of a method for evaluating the spatial accessibility conditions and their results. For this, we sought to support the theoretical foundation about the main issue involved and legislation. From the method used--guided walks--it was possible to identify the main barriers to accessibility in historic buildings. From the identified barriers, possible solutions are presented according to the four components of accessibility: spatial orientation, displacement, use and communication. It is hoped also that the knowledge gained in this research contributes to an improvement of accessibility legislation in relation to the listed items. PMID- 22317297 TI - Ergonomic analysis of the use of open-plan offices in Brazilian public sector offices. AB - The open-plan office is a layout used in government offices in Brazil aimed at saving on space occupied and integrating employees. However, the design of these work-stations must follow the characteristics of tasks and their interrelationships, since adverse physical and organizational conditions may have a negative impact on work productivity. From this perspective, this study sought to identify, from the viewpoint of the ergonomics of the built environment, the adequacy of the open-plan government offices for financial auditing accounts and analyzing documents. Use was made of the Ergonomic Methodology for Evaluating the Built Environment--MEAC (in Portuguese) which systematically analyzes the physical space, by using a mix of physical-spatial assessments and tools for identifying how the environment is perceived. The MEAC was employed in three analytical phases of the physical aspects, namely: an analytical phase of the user's perception; a diagnostic phase; and a final phase of propositions. PMID- 22317298 TI - Study and analysis of occupational risk factors for ergonomic design of construction worksystems. AB - Manual material handling (MMH) is unavoidable because of the nature of jobs or tasks as and man-machine interfaces in a construction worksystem. Data were collected from six strata of workers viz., masons, mason helpers, carpenters, welders, gas cutters and ground-level helpers (259 out of 700 workers) from a construction site of a steel plant located in India to analyze different types of occupational risk factors, such as awkward posture, repetitive movements and others associated with MMH activities to assess their impact on musculoskeletal disorders (MSDs). It is essential that these risk factors are required to be under control through application of ergonomics-based design approaches for construction worksystem. In this context, multinomial logistic regression analyses were used to identify the significant risk factors among the workers. The results shows that masons, mason helpers, carpenters, welders/gas cutters and ground-level helpers are greatly affected by static body posture, type of tools used, excessive stress due to repetition, awkward postures and extreme climate, respectively. Appropriate preventive and corrective measures are suggested for minimization of risks associated with such jobs/tasks to improve health and performance of the workers. PMID- 22317299 TI - Evidence-based exposure criteria for work-related musculoskeletal disorders as a tool to assess physical job demands. AB - Despite worldwide attention, musculoskeletal disorders (MSDs) remain a substantial concern at work. To support ergonomists to assess the work-related risk factors for MSDs, several instruments are available. Unfortunately, many of these instruments are not supported by evidence-based exposure criteria for particular MSDs. For effective prevention of MSDs, it is important to know to what extent work-related risk factors are present in the work situation. The Netherlands Center for Occupational Diseases (NCOD) develops evidence-based criteria documents for the assessment of work-related MSDs. The exposure criteria of these documents can be used on a group level to support ergonomists in their assessment of the physical job demands that are associated with work-related MSDs. At the moment the NCOD has exposure criteria for the assessment of 22 work related MSDs, for instance on the work-relatedness of upper extremity disorders, non-specific low back pain or patellar tendinopathy. The use of these exposure criteria enables ergonomist to better assess the work-related risks of MSDs as a starting point for effective prevention. PMID- 22317300 TI - Construction and application of an indicator system to assess the ergonomic performance of large and medium-sized construction companies. AB - This article proposes a system of indicators to evaluate the performance of companies in ergonomics for buildings. The system was developed based primarily on studies related to the performance evaluation of the construction industry and on Brazilian standards of ergonomics and work safety and had also the contribution of national and international indicators related to ergonomics, work safety, quality, sustainability, quality of work life and to organizational behavior. The indicators were named, classified and their components were assigned to compose the theoretical model SIDECE--System of Performance Indicators in Ergonomics for Building Construction (as for the Portuguese acronym), serving the major goals of ergonomics: health, safety and workers' satisfaction and production efficiency. The SIDECE is being validated along with the building construction companies in the city of Natal, Brazil, whose practical results, deriving from the application of instruments to collect field data, are under process, to be presented on the occasion of the 18th World Congress on Ergonomics. It is intended that the SIDECE be used by building construction companies as a support tool for excellence management. PMID- 22317301 TI - Outcomes of a revised apprentice carpenter fall prevention training curriculum. AB - Falls from heights are a leading cause of morbidity and mortality among construction workers, especially inexperienced workers and those performing residential construction. This research reports changes in fall prevention behaviors following revision of fall prevention training in a union-based carpenters' apprenticeship program. We used a comprehensive needs assessment to identify gaps in apprentice carpenters' preparation to work at heights, used these results to guide a school-based fall prevention curriculum to fill these gaps, and measured the effects of the revised curriculum on knowledge, beliefs, and fall prevention behaviors. PMID- 22317302 TI - Casting an ergonomic eye on university libraries. AB - Research in the field of Ergonomics of the Built Environment has been developed with a view to consolidating studies in this area, the objective of which is to provide evidence that the joint participation of users and designers on drawing up projects is important. In this context, the theme of this study is to investigate the interactions between users and the environment in a university library. To do so, well-established techniques from Ergonomics, Architecture and Environmental Psychology were used to make a functional and behavioral evaluation to identify the level of user satisfaction in six libraries in the various study centers of the Federal University of Pernambuco in Recife, northeast Brazil, so as to identify the strengths and also weaknesses in these spatial structures. PMID- 22317303 TI - The impact of a 'green' building on employees' physical and psychological wellbeing. AB - Multiple claims and some empirical findings suggest that 'green' buildings should be healthier (psychologically and physically) and promote greater productivity than conventional buildings. The empirical evidence in this regard over the last decade or so has been inconclusive suggesting either that the studies are flawed or that there are specific aspects of green buildings that promote wellbeing and productivity and others that do not. This study looks at a longitudinal comparison of two groups; a group that moved into South Africa's first GreenStar accredited building and a group that did not. Measures were taken before the move and six months later. Results demonstrated that the 'green' building did not produce significantly better physical or psychological wellbeing, or higher perceived productivity. These results are discussed in relation to suggestions for what design features to focus on that may produce significant results. PMID- 22317304 TI - Using process evaluation to determine effectiveness of participatory ergonomics training interventions in construction. AB - The construction industry continues to experience high rates of musculoskeletal injuries despite the widespread promotion of ergonomic solutions. Participatory ergonomics (PE) has been suggested as one approach to engage workers and employers for reducing physical exposures from work tasks but a systematic review of participatory ergonomics programs showed inconclusive results.. A process evaluation is used to monitor and document the implementation of a program and can aid in understanding the relationship between the program elements and the program outcomes. The purpose of this project is to describe a proposed process evaluation for use in a participatory ergonomic training program in construction workers and to evaluate its utility in a demonstration project among floor layers. PMID- 22317305 TI - Ergonomic aspects to be considered in planning public spaces destined for elderly people. AB - As has happened in many other countries, Brazil has also witnessed an evident change in the question of accessibility over the last twenty years. In line with this theme, that of old age has only become evident in the last two decades. For a long period of time, the elderly have been systematically ignored as an object of investigation and have not been contemplated with consistent public social policies. Therefore, the main objective of this research is to verify the conditions of physical accessibility that allow the elderly to use public spaces, taking as a study case the Sao Goncalo square and the Solon de Lucena Park, in the city of Joao Pessoa--PB, identifying the biological and functional losses suffered by elderly people due to the aging process and verifying the specific physical needs of this segment of the population. Qualitative methods were adopted, such as systematic observations with the production of behaviour maps, in addition to a review of the literature and analysis of the data. The research identified problems related to the physical accessibility of the elderly to public spaces that generate difficulties for displacement, use, information and orientation, contributing to the planning and ergonomic guidelines which aim at improving these environments, such as the use of different and contrasting colours on the urban furniture and floor, for example. PMID- 22317306 TI - Anthropometric evaluation of internal horizontal circulation environments. AB - The relevant research is questioning the essence of the existence of an adequate internal circulation to human dimensions. The research was based on the method of anthropometric assessment of internal circulation de Barros (2009), which was applied in three different sizes of apartments in the city of Caruaru-PE. These apartments were evaluated through the floor plans and furniture layouts, suggested by the builders, with the use of anthropometric models in simulation of movement. The study found that traffic problems are not just a consequence of small rooms, but projects that do not bother to match the anthropometric measurements to the space environment. PMID- 22317307 TI - Accessibility for all: going from theory to practice. AB - The present work demonstrates, through a case study, the importance of theoretical knowledge in practical application of spatial accessibility in order to guarantee equal conditions for all people in the movement and use of space. Initially there was a literature review on the accessibility of space and how design in a accessible way. Next, we show one makeover proposal in one public school that wants to provide access to people with disabilities. This makeover was done and so we could evaluate the buildings changes through the method of accompanied walk with two people. Finally we present the main results and discussions. PMID- 22317308 TI - Systems approaches to risk assessing healthcare, how far have we come? AB - Systems approaches and their relevance to risk assessment are considered through an examination of a number of recent applications in England. The importance of visual mapping of systems is emphasised. This approach encourages participation from those within the system with less technical knowledge but with important information to add to a risk assessment. Other advantages outlined include the ability to readily identify system boundaries, map processes and record both strengths and weaknesses of existing or planned system changes. The use of risk assessment methods with this approach should be cautious, as any one method may only identify a sub-set of all risks. PMID- 22317309 TI - Sociotechnical systems approach to healthcare quality and patient safety. AB - The SEIPS (Systems Engineering Initiative for Patient Safety) model of work system and patient safety is described and selected research and practical applications are presented. PMID- 22317310 TI - Performance-based management and quality of work: an empirical assessment. AB - In France, in the private sector as in the public sector, performance-based management tends to become a norm. Performance-based management is supposed to improve service quality, productivity and efficiency, transparency of allotted means and achieved results, and to better focus the activity of employees and of the whole organization. This text reports a study conducted for the French Ministry of Budget by a team of researchers in ergonomics, sociology and management science, in order to assess the impact of performance-based management on employees, on teams and on work organization. About 100 interviews were conducted with employees of all categories and 6 working groups were set up in order to discuss and validate or amend our first analyses. Results concern several aspects: workload and work intensification, indicators and performance management and the transformation of jobs induced by performance management. PMID- 22317311 TI - Fundamentals of systems ergonomics. AB - Ergonomics/human factors is, above anything else, a systems discipline applying a systems philosophy and systems approaches. Many things are labeled as "systems X" in today's world, and this paper specifies just what attributes and notions define ergonomics/human factors in systems terms. These are concern for context, acknowledgement of interactions and complexity, a holistic approach, recognition of emergence and embedding of the professional effort involved within organization systems. These five notions are illustrated with examples from a large body of work on rail human factors. PMID- 22317312 TI - Strategies and arguments of ergonomic design for sustainability. AB - Referring to the discussion recently promoted by the Sub-Technical Committee n degrees 4 "Ergonomics and design for sustainability", in this paper will be shown the early results of a theoretical and methodological study on Ergonomic design for sustainability. In particular, the research is based on the comparison between the common thematic structure characterizing Ergonomics, with the principles of Sustainable Development and with criteria adopted from other disciplines already oriented toward Sustainability. The paper identifies an early logical-interpretative model and describes possible and relevant Strategies of Ergonomic design for sustainability, which are connected in a series of specific Sustainable Arguments. PMID- 22317313 TI - Toward a transdisciplinary approach of ergonomic design for sustainability. AB - Starting from the results of a theoretical and methodological study on Ergonomic design for sustainability previously developed from the authors, this paper shows the early results of a study that tries to apply them to actual operational and conceptual apparatuses of Ergonomics. In particular, the research aims to verify the possibility for Ergonomics to initiate an update of its current theoretical and procedural tools, towards new design solutions of "sustainable well-being", trying to look for new declinations of its several fields of application. The paper identifies new paradigms and definitions for one of the central themes of ergonomic design, as well as one among the most established and investigated: the usability of products and services. PMID- 22317314 TI - Ergonomics and sustainability in the design of everyday use products. AB - The relationship between Ergonomics and Design is a key element in the sustainability project, as well as in many other areas of experimental design. In the Design for Sustainability field, Ergonomics is a strategic factor for design culture innovation, providing designers with the necessary knowledge and skills regarding human characteristics and capabilities, as well as user needs and desires during use and interaction with products in work activities and everyday life. Ergonomics is also a strategic innovative factor in design development and manufacturing processes. In fact, ergonomics provides a methodological approach in user-product interaction evaluation processes through the use of participatory design and survey methods, user trials, direct observation, savings and resource conservation, etc.On the other hand, design offers solutions able to interpret user needs and expectations, at the same time suggesting new behaviors and lifestyles.In Design for Sustainability, the ergonomic and user-centered approach contributes greatly to lifestyles and innovative use of products--making it possible to understand and interpret real people needs and expectations in their everyday actions and behavior.New consumption patterns, new awareness of lifestyles, energy source consumption, purchasing methods and consumption style etc. can be supported by design innovation, responding to expressed and unexpressed user needs. With this in mind, the ergonomic approach represents the starting point for design choices and at the same time, a tool for assessing their appropriateness and effectiveness. PMID- 22317315 TI - Ergonomics and design for sustainability in healthcare: ambient assisted living and the social-environmental impact of patients lifestyle. AB - This work presents considerations on Ergonomics and Design for Sustainability in the healthcare field based on research experiences of the Technology and Design for Healthcare (TeDH) research group of INDACO (Industrial design, communication, arts and fashion) department of Politecnico di Milano. In order to develop a multidisciplinary approach to design able to answer to specific user needs such as elderly in an environmental sustainable way (1) this paper shows the results we achieved concerning ergonomics and environmental impact in product development (2), the extension of this approach to interior and home design and the advantage of the application of Information Communication Technologies (ICT). ICT can help people with special needs to make their everyday life easier and more safe, at the same time, ICT can make social-environmental impact of everyday behavior evident and can be applied to manage sustainability. The specific theme is thus to integrate ergonomics and sustainability competences in the development of Ambient Assisted Living through a Product- Service System approach. The concept of product service system has the potential to improve product performances and services, establish new relations and networks with different actors in order to satisfy user needs and apply a systems approach considering environmental, social and economic factors in the users' environment. PMID- 22317316 TI - Sustainability and accessibility: the Design for All approach. AB - A sustainable project should also be affordable, and it is cheaper if it its affordability is guaranteed to as much people as possible since the first phases of the project without any modifications. The author illustrates the activity of diffusion of DfA on an urban scale carried out on didactic and cultural level. PMID- 22317317 TI - Early variability in the conceptualisation of "sustainable development and human factors". AB - The sub-discipline of "sustainable development and human factors" is relatively new, first being used in 2006 with a Technical Committee of the IEA being established only in 2009 and a similar special interest group on "green ergonomics" at the Institute of Ergonomics and Human Factors being established in 2010. In general though, the definitions and practice of "sustainable development" is highly contentious and ambiguous across a range of disciplines. This paper examines the diversity of definitions and approaches to sustainable development and human factors in the early papers in this sub-discipline. An examination of 45 chapters and papers (from 2008 to 2011) reveals a surprising consistency in the definitions used for sustainable development but also a large proportion of the papers where no definitions are given at all. The majority of papers were, however, biased towards an economic capital and social capital emphasis, which is to be expected of work traditionally in the ergonomics paradigm. Further, most papers were theoretical in nature demonstrating a great opportunity for empirical work. The variability in definitions is discussed in relation to the future challenges facing the growth of this emergent sub discipline and opportunities for further theoretical and empirical work. PMID- 22317318 TI - Defining elements of sustainable work systems--a system-oriented approach. AB - Based on a system-theoretic discussion of sustainability, this paper aims to develop a conceptual model of a sustainable work system which is consistent with the definition of ergonomics by the IEA in 2000 (but also with earlier definitions) as well as with the triple bottom line understanding of sustainable development - comprising the management of human, social, ecological and economic capital in a balanced manner. PMID- 22317319 TI - Ergonomics and sustainability--challenges from global supply chains. AB - The development of globalised supply chains is a major challenge for sustainability. For several years, there has been discussion within the profession whether and how ergonomics and human factors can play a role. Based on our research, we have identified five major challenges from global supply chains especially related to the social aspects of sustainability: (1) criteria for social sustainability, (2) the role of key performance indicators in the management of supply chains, (3) the constant changes in supply chains, (4) the challenge in establishing participation, and (5) the development of agency and regulatory mechanisms. There are obviously no clear and simple solutions to these challenges. One possible avenue for progress might lie in acquiring a greater understanding of the challenges from global supply chains and developing a strategy which combines social and long-term business sustainability. Starting from such a basis, the next step would be to find ways for the ergonomics and human factors community to create international collaboration which can impact specific global supply chains. PMID- 22317320 TI - Shared services centers and work sustainability: which contributions from ergonomics? AB - This study examines the way in which Shared Services Centers (SSCs) were implemented in a French multinational company. It aims to characterize the change according to the capabilities model developed by Amartya Sen: what are the effects of SSCs in terms of capabilities development and developmental quality of work, i.e. in the enabling potential of work? A 3-step methodology has been used: first, an investigation was conducted in a pay service of a local entity moving into SSC in 2013; second, two investigations were conducted in another pay service of a SSC: first, a few months after the change, and then, one year after the change (the same operators were interviewed). Results show a tendency to the decrease of the enabling potential. Additionally, it was noted that administrators are kept away from the design process and have to struggle with inappropriate rules. The efficiency and sustainability of the SSC are questioned; in this context, the human factor specialist has an important role to play. PMID- 22317321 TI - Ergonomic principles and tools for best interdisciplinary psycho-physical stress prevention. AB - The psycho-physical stress is a risk to all intents and purposes,finally acknowledged, it requires increasing attention. Measures forits protection are reflected in the appropriate application of organizational policies on a human scale, or in respect of the"macro-ergonomics". This work consists on several inter-disciplinary tools available to the proper prevention, outbreaks of work related stress.During work, adequate rests are important to prevent work related physical and mental fatigue. The strategies for maintaining a healthy balance between work rate and work breaks, may differ depending on the individual, subjective habits and peculiarities related to the work environment. Resting does not necessarily mean "going to break". The break-time is important as the work time. While the latter is regulated, the first is not always clearly defined, though necessary. Knowing the employment contract is the first step towards the implementation of their rights relating to periods of suspension from the activity of work is also essential for high performance working. Breathing exercises, massage therapy, biofeedback, role-playing are some of the tools used during work breaks to prevent mental and physical fatigue. At the end music has a rhythm by alternating strong and weak accents. If the musical notes represent the "vertical" trend of music (melody), figures and pauses, inserted into the rhythmic structure of the measure, regulate the duration of sounds over time and determine the "horizontal" trend of a song. Transferring this concept on work, is meant to understand, using a metaphor, the importance of respect of changes in both vertical and horizontal trends inside a cycle. PMID- 22317322 TI - Innovation in user-centered skills and performance improvement for sustainable complex service systems. AB - In order to leverage individual and organizational learning and to remain competitive in current turbulent markets it is important for employees, managers, planners and leaders to perform at high levels over time. Employee competence and skills are extremely important matters in view of the general shortage of talent and the mobility of employees with talent. Two factors emerged to have the greatest impact on the competitiveness of complex service systems: improving managerial and employee's knowledge attainment for skills, and improving the training and development of the workforce. This paper introduces the knowledge based user-centered service design approach for sustainable skill and performance improvement in education, design and modeling of the next generation of complex service systems. The rest of the paper cover topics in human factors and sustainable business process modeling for the service industry, and illustrates the user-centered service system development cycle with the integration of systems engineering concepts in service systems. A roadmap for designing service systems of the future is discussed. The framework introduced in this paper is based on key user-centered design principles and systems engineering applications to support service competitiveness. PMID- 22317323 TI - A toolkit for MSDs prevention--WHO and IEA context. AB - Many simple MSD risk management tools have been developed by ergonomists for use by workers and employers with little or no training to undertake injury prevention programs in their workplace. However, currently there is no "toolkit" which places such tools within an holistic, participative ergonomics framework and provides guidance on how best to use individual tools. It is proposed that such an holistic approach should entail initial analysis and evaluation of underlying systems of work and related health and performance indicators, prior to focusing in assessment of MSD risks stemming from particular hazards. Depending on the context, more narrowly focused tools might then be selected to assess risk associated with jobs or tasks identified as problematic. This approach ensures that biomechanical risk factors are considered within a broad context of organizational and psychosocial risk factors. This is consistent with current research evidence on work- related causes of MSDs. PMID- 22317324 TI - Conceptual framework for development of a toolkit for prevention of work-related musculoskeletal disorders. AB - The World Health Organisation (WHO) network of Collaborating Centres in Occupational Health aims to promote the development, implementation use of "toolkits" for workplace use in reducing the risk of injuries and disease. As a major partner within this network, the International Ergonomics Association is committed to developing a toolkit to reduce the risk of musculoskeletal disorders. This paper outlines the kind of conceptual framework required to support this work. PMID- 22317325 TI - IEA/WHO toolkit for WMSDs prevention: criteria and practical tools for a step by step approach. AB - When studying WMSDs, several determinants and their interrelationship are considered as relevant. Hence the necessity of an "holistic" approach to prevention, especially when preparing technical rules and strategic plans. There is a strong request, from OSH agencies and operators, for developing "simple" tools for risk assessment and management. In this context WHO asked IEA to develop a "Toolkit for WMSD prevention". The paper presents one of the main contribution to this WHO project, focused on selecting tools at different level for hazard identification, risk estimation and management. Proposals are based on two essential criteria: Acting on a step-by-step approach; Taking into account the presence of multiple influencing factors. The proposals consider: A Basic Step devoted to hazard identification by operative "key-enter" questions, that can be operated also by non-experts. A First Step, (quick assessment), for identifying 3 possible conditions: acceptable; high risk present; more detailed analysis (via tools presented at second step) necessary. This step can be operated by non-experts with only some specific training. A Second Step, where recognized (i.e. from international standards or guidelines) tools for risk estimation are used. This step can be operated only by persons with some specific training. PMID- 22317326 TI - Categorizing job physical exposures using simple methods. AB - Work-related musculoskeletal disorders (WMSDs) are debilitating for workers and costly for employers. Existing exposure assessment tools were modified for rapid job physical exposure and company organizational exposure assessment. These were augmented with injured worker interviews to "put the meet on the bones" in characterizing risk. These risk assessments are conducted in all industry sectors. PMID- 22317327 TI - A simple tool for preliminary hazard identification and quick assessment in craftwork and small/medium enterprises (SME). AB - During the last Congress of the International Ergonomics Association (IEA), Beijing, August 2009, an international group was founded aimed at developing a "toolkit for MSD prevention" within IEA and in collaboration with World Health Organization (WHO). Possible users of toolkits are: members of health and safety committees, health and safety representatives, line supervisors; labor inspectors; health workers implementing basic occupational health services; occupational health and safety specialists.According to ISO standard 11228 series and the new Draft CD ISO 12259-2009: Application document guides for the potential user, a computer software ( in Excel(r)) was create dealing with hazard "mapping" in handicraft The proposed methodology, using specific key enters and quick assessment criteria, allows a simple ergonomics hazard identification and risk estimation. Thus it makes possible to decide for which professional hazards a more exhaustive risk assessment will be necessary and which professional consultant should be involved (occupational physician, safety engineer, industrial hygienist, etc.). PMID- 22317328 TI - Hazard identification and pre-map with a simple specific tool: synthesis of application experience in handicrafts in various productive sectors. AB - In August 2009, an international group was founded with the task of developing a "toolkit for MSD prevention" under the IEA and in collaboration with the World Health Organization.According to the ISO standard 11228 series and the new Draft ISO TR 12259 "Application document guides for the potential user", our group developed a preliminary "mapping" methodology of occupational hazards in the craft industry, supported by software (Excel(r), free download on: www.epmresearch.org).The possible users of toolkits are: members of health and safety committees; health and safety representatives; line supervisors; foremen; workers; government representatives; health workers providing basic occupational health services; occupational health and safety specialists.The proposed methodology, using specific key enters and quick assessment criteria, allows a simple ergonomics hazards identification and risk estimation to be made. It is thus possible to decide for which occupational hazards a more exhaustive risk assessment will be necessary and which occupational consultant should be involved (occupational physician, safety engineer, industrial hygienist, etc.).The methodology has been applied in different situations of small and medium craftsmanship Italian enterprises: leather goods, food, technical dental work, production of artistic ceramics and stained glass, beekeeping activities. The results are synthetically reported and discussed in this paper. PMID- 22317329 TI - Biomechanical overload in multiple tasks with weekly and annual cycle: practical experiences in the field of cleaning and packaging of fruit. AB - The OCRA method is the reference method chosen in ISO (ISO 11228-3) and CEN (EN 1005-5) standards regarding risk assessment and management of upper limbs repetitive movements and exertions. The method consists of two specific tools (OCRA index and OCRA checklist). In this paper special attention will be devoted to the procedures for the analysis of multiple repetitive tasks.When computing the OCRA index (checklist score) considering the presence of more than one repetitive task, a "traditional" procedure has been previously proposed. This approach, whose results could be defined as "time weighted average", seems to be appropriate when considering rotations among tasks that are performed almost once every hour. On the contrary, when rotation among repetitive tasks is less frequent the "time weighted average" approach could result into an underestimation of the exposure level. For those scenarios an alternative approach is based on a concept that the most stressful task is the minimum starting point. A peculiar procedure allows to exactly estimate the resulting index within this range of minimum to maximum values. It is possible to apply this approach also for job rotation with weekly or monthly or annual cycle typical of agriculture, supermarket, cleaning sectors. This paper shows criteria and results in two working situation: cleaning (weekly cycle) and packaging of fruit (annual cycle). PMID- 22317330 TI - Study of biomechanical overload in urban gardeners of Barcelona: application of analytical models for risk exposure evaluation in annual working cycle. AB - Occupational musculoskeletal disorders in the upper limbs and its consequences on the impact and prevalence in the work force are subject of many investigations in almost all the production fields. However, the exposure to this kind of risk factor on urban gardeners has not been well studied so far. The kind of plant varieties used in the parks, the tools that they use, as much as the necessary actions for the maintenance of the park, have an impact on the biomechanical overload of the upper limbs. Additionally, the analysis of the exposure to the biomechanical overload on upper limbs in gardening work is a complex task, mainly because it is an activity highly variable and of annual cycle. For this reason an analytical model for risk exposure evaluation is necessary. During this research the work activity of 29 gardeners in 3 urban parks of Barcelona has been analyzed. Each park has a specific acting plan, in relation with the quantity and the typology of vegetal species, its classification and the season of the year. Work and observation and video recording sessions on-site were conducted. The video-graphic registration was done on workers without any prior musculoskeletal disorder and with a minimum labour experience of 5 years. Moreover, the analysis of saturation time, considered as the relation of the repetitive working hours in reference with the hours of effective work was done. Using the registered tasks on video, the biomechanical overload on upper limbs applying the OCRA Checklist method was analyzed. RESULTS: A methodological procedure to analyze the risk exposure in annual working cycle has been proposed. The results that we got allow us to get information that can help in the assignment of the tasks and in the training of staff, as well as in the recommendations of the urban landscape's design. All these aspects have the goal to decrease the risk to develop work related musculoskeletal disorders. PMID- 22317331 TI - Application of the OCRA Method in the sugar cane harvest and its repercussion on the workers' health. Preliminary study. AB - In Brazil the sugar ethanol industry has had strong growth in the last 10 years, sometimes due to the growing sugar exportation, sometimes due to the alcohol production for automobile fuel and for exportation. Despite the growing mechanization of the raw material harvest (sugar cane), the manual work still persists. The development of this article was based in the application of the OCRA Method in the sugar cane harvesting process, to evaluate the risks to the upper limbs by repetitive movements and epidemiologically prove the ratio risk x harm to the heath of the workers, as well as the probability of developing improvements in the working conditions. The analysis process consists of studying the work organization, the risks to the health of the worker and the distribution of the recovery periods during the working day. PMID- 22317332 TI - New risk assessment tools in The Netherlands. AB - In this paper an introduction to and description of the risk assessment tools that are freely available for companies in The Netherlands is given. It is explained in what way the tools can and should be used and how the level I checklist for physical load and the level II instruments are related. The two instruments that -in 2011- made this 'Dutch toolbox' complete, are the checklist physical load and the Working Posture Risk Assessment Tool (WRAP 1.0). The content, the development process and some examples of these tools are explained. The toolbox is complete but does need additional evaluation to improve the quality of the assessments and the usability in practice. PMID- 22317333 TI - New tools in Germany: development and appliance of the first two KIM ("lifting, holding and carrying" and "pulling and pushing") and practical use of these methods. AB - The Key Indicator Methods (KIM) assess the risk of manual handling of loads on a screening level. Their purpose is the recognition and removal of job design deficits. The risk assessment is carried out in two stages. The first stage is the ordinal scaled description of workload items. The second stage is the evaluation of the degree of probability of physical overload. The intended user population are both practitioners in enterprises such as safety engineers, industrial engineers, and inspectors. The first two KIM were developed and tested from 1996 to 2001 in connection with the implementation of the EU directives into German national legislation. They consist of two independent, but formally adaptable methods for lifting, holding, and carrying and for pulling, and pushing. The KIM were drafted in the German Federal Institute for Occupational Safety and Health (BAuA) in close collaboration with the German Labour Inspectors. Numerous companies, scientists, statutory accident insurances, institutions, employer associations, and trade unions were involved. Since their first publication in 2000 and 2001, these methods are widely accepted among possible users with a corresponding broad application in Germany. They are recommended by the EU Labour Inspector Conference for application. In 2007 a third KIM for manual handling operating tasks KIM MHO were developed, tested, and validated in the last four years. PMID- 22317334 TI - Evaluation of objectivity, reliability and criterion validity of the key indicator method for manual handling operations (KIM-MHO), draft 2007. AB - Upper extremity musculoskeletal symptoms and disorders are common in the working population. The economic and social impact of such disorders is considerable. Long-time, dynamic repetitive exposure of the hand-arm system during manual handling operations (MHO) alone or in combination with static and postural effort are recognised as causes of musculoskeletal symptoms and disorders. The assessment of these manual work tasks is crucial to estimate health risks of exposed employees. For these work tasks, a new method for the assessment of the working conditions was developed and a validation study was performed. The results suggest satisfying criterion validity and moderate objectivity of the KIM MHO draft 2007. The method was modified and evaluated again. It is planned to release a new version of KIM-MHO in spring 2012. PMID- 22317335 TI - HARM overview and its application: some practical examples. AB - The Hand Arm Risk Assessment Method (HARM 1.0) has been developed for occupational health officers to perform risk assessments of developing arm, neck or shoulder pain during hand arm tasks. The tool can also help in finding solutions for risk reduction and estimating their effect on the risk level. In this paper the status of affairs and the practical application of HARM is described. The usage of HARM is explained and illustrated with the risk assessment of a specific hand arm task. In addition, the experiences with the application of HARM by a stone factory in The Netherlands are described. PMID- 22317336 TI - A protocol for evaluating the accuracy of 3D body scanners. AB - Scan-derived landmarks locations and surface shapes are more and more used, but there is no commonly accepted protocol for evaluating the accuracy of these measurements. Therefore we propose a protocol for evaluating the accuracy of surface shape and the repeatability of scan-derived landmark locations. According to existing Japanese and German domestic standards, we propose to use an artefact (e.g. sphere with diameter of about 120 mm) calibrated very accurately for evaluating the accuracy of scanner-systems. For evaluating the repeatability of landmark locations, we propose to use an anthropomorphic dummy with landmark locations premarked. These test objects are measured by a 3D body scanner to be evaluated. Evaluation parameters such as trueness, precision, and repeatability are calculated from the measured data. A round-robin test was conducted in six different institutes using 17 body/head/foot scanners produced by eight companies. The purposes of the roundrobin test were to evaluate the availability of test objects to different body scanners, and to examine the measurement locations of test objects and quality parameters to be reported. As a result, the proposed test objects could be measured and the data exported by all scanner systems except one, which could not export the ball measurement. For a comparative purpose, a figure of measured surface might be useful. PMID- 22317337 TI - Where is the human waist? Definitions, manual compared toscanner measurements. AB - Where exactly is the human waist? How do definitions work for women who deviate from the conventional body shape? Does the measuring instrument matter? Waist is conventionally understood to be a measurable zone within the abdominal region of the torso, a zone of considerable importance. There needs to be a good consistent waist definition, one accurate and valid for everyone. Incorrect definition and measurement will result in technical errors, commercial wastage and customer dissatisfaction. This paper investigates the waist's location and size from the point of view of garment construction for 90 adult women scanned and manually measured in a breast reduction study at Flinders Medical Center, South Australia. There are differing definitions of the location of the human waist as well as different measuring instruments. This study compares:* Two definitions:* ISO 8559, 2.1.11 and * CAESAR, Waist Circumference Preferred.* Two different instruments:* the traditional tape measure, and * software-extracted computer aided anthropometry (CAA). Substantial discrepancies between the results from these two locations-definitions were found. The choice of instrument used seriously affects the measurement obtained. This study demonstrates three things:* waist is not horizontal for a significant sub group of the population,* CAA extracted waist measurements are not accurate (same as real values) or valid (measures the characteristic) for a sub group, and * manually measured CAESAR Preferred Waist accurately and validly measured all individuals studied. There is a clear need to modify ISO waist definition for garment construction to include the full range of anatomical variation encountered amongst women. PMID- 22317338 TI - Comparing swimsuits in 3D. AB - In competitive swimming, suits have become more important. These suits influence friction, pressure and wave drag. Friction drag is related to the surface properties whereas both pressure and wave drag are greatly influenced by body shape. To find a relationship between the body shape and the drag, the anthropometry of several world class female swimmers wearing different suits was accurately defined using a 3D scanner and traditional measuring methods. The 3D scans delivered more detailed information about the body shape. On the same day the swimmers did performance tests in the water with the tested suits. Afterwards the result of the performance tests and the differences found in body shape was analyzed to determine the deformation caused by a swimsuit and its effect on the swimming performance. Although the amount of data is limited because of the few test subjects, there is an indication that the deformation of the body influences the swimming performance. PMID- 22317339 TI - A multidimensional approach to the generation of helmets' design criteria: a preliminar study. AB - The design and development process of helmets incorporates systematically design criteria related to safety to accomplish European and local standards for the commercialization. However, there are few studies focused on user's comfort and adaptation. Present study tackles a multidimensional approach to gain better understanding of the interaction between helmet and user to generate design criteria for the internal helmet surface. Morphological characteristics of the target population, pressure distribution over head and subjective perception of fitting and discomfort are the factors considered to establish the criteria that assure a proper fit. Ten men corresponding to helmet size M and usual drivers of motorbike wore two helmet models in three sizes (S, M and L). The head shape of participants was acquired using the head scanner of I-Ware laboratory and an instrumented pad was used to measure pressure in five head regions. After wearing the helmet, users filled in a perception questionnaire about fitting, comfort and usability considering the five regions. Users' fitting perception provided the relation between pressure levels and the comfort felt in the five regions. This study constitutes a first approach to a new methodology to generate criteria to improve the design of helmets under a multidimensional approach. PMID- 22317340 TI - Measurement of breast volume using body scan technology(computer-aided anthropometry). AB - Assessment of breast volume is an important tool for preoperative planning in various breast surgeries and other applications, such as bra development. Accurate assessment can improve the consistency and quality of surgery outcomes. This study outlines a non-invasive method to measure breast volume using a whole body 3D laser surface anatomy scanner, the Cyberware WBX. It expands on a previous publication where this method was validated against patients undergoing mastectomy. It specifically outlines and expands the computer-aided anthropometric (CAA) method for extracting breast volumes in a non-invasive way from patients enrolled in a breast reduction study at Flinders Medical Centre, South Australia. This step-by-step description allows others to replicate this work and provides an additional tool to assist them in their own clinical practice and development of designs. PMID- 22317341 TI - Photogrammetry procedures applied to anthropometry. AB - This study aims to evaluate the reliability and establish procedures for the use of digital photogrammetry in anthropometric measurements of the human hand. The methodology included the construction of a platform to allow the placement of the hand always equivalent to a distance of the camera lens and to annul the effects of parallax. We developed a software to perform the measurements from the images and built up a subject of proof in a cast from a negative mold, this object was subjected to measurements with digital photogrammetry using the data collection platform in caliper and the Coordinate Measuring Machine (MMC). The results of the application of photogrammetry in the data collection segment hand, allow us to conclude that photogrammetry is an effective presenting precision coefficient below 0.940. Within normal and acceptable values, given the magnitude of the data used in anthropometry. It was concluded photogrammetry then be reliable, accurate and efficient for carrying out anthropometric surveys of population, and presents less difficulty to collect in-place. PMID- 22317342 TI - Using digital photogrammetry to conduct an anthropometric analysis of wheelchair users. AB - This study deals with using digital photogrammetry to make an anthropometric analysis of wheelchair users. To analyse the data, Digita software was used, which was made available by means of the agreement of the Design Department of the Federal University of Pernambuco--Brazil--with the Department of Ergonomics of the Technical University of Lisbon--Portugal. Data collection involved a random sample of 18 subjects and occurred in the Biomechanics Laboratory of the Maurice of Nassau Faculty, located in Recife, Pernambuco. The methodology applied comprises the steps of Ergonomic Assessment, Configuration of the Data Base, Taking Digital Photographs, Digitalising the Coordinates and Presentation of Results. 15 structural variables related to static anthropometry were analysed, and 4 functional range variables relating to dynamic anthropometry. The results were presented by analysing personal data, classified by gender, ethnicity and age; by functional analysis of the sample, classified by clinical diagnosis, results of assessing the joints, results of the evaluation through motion and postural evaluation; and of the analysis of the anthropometric sample, which indicated for each variable the number of people, the mean, the standard deviation, and the minimum, median and maximum values. PMID- 22317343 TI - Automatic anthropometric personalization of a digital human model from a set of subject's photographs. AB - The objective of the work is to develop a method for automatic dimensioning of a digital human model (DHM) from a set of calibrated photographs of the subject under study. Fifteen subjects (10 males, 5 females, mean age 27) wearing surface retro-reflective markers at major bony landmarks and standing inside a calibrated space, were photographed by means of low cost main stream digital cameras (face, left and right views). The DHM software used is based on a skeletal structure surrounded by contours defined by cross sections along the skeletal links. Specific points corresponding to bony landmarks are defined in body linkage local reference frames. The photograph calibration method (DLT) allows to superimpose a picture of the DHM on the subject's photographs. A specific algorithm adjusts the length of the manikin skeletal links in function of the measured distance between markers attached to these links (e.g. knee and ankle for the lower leg). Then the contour sections dimensions were adjusted to fit subject's silhouette extracted from the photographs. The results obtained within a few seconds of calculation consist of a personalized DHM representing the subject with an error less than 2% for stature and less than 4% for weight. PMID- 22317344 TI - An anthropometric survey using digital photogrammetry: a case study in Recife, Pernambuco, Brazil. AB - This study was carried out in a partnership with the Federal University of Pernambuco and the Faculty of Human Motricity of the Technical University in Lisbon (Portugal). The aim of the study was the measurement of human body segments throughout the digital photogramety, comparing and analysing data into Recife sample and to validate the Digital System as anthropometric survey tool. The result of the analysis has introduced: Data from the sample; Data by age; Data by Sex; Data by ethnicity; Data by region of birth; Difference of data from population individually. Besides to prove the true efficiency of the software. PMID- 22317345 TI - Structuring software anthropometric variables on CD Rom as a facilitator of the process of design of work situations. AB - The environment where everyday activities are developed, these should be appropriate and the individual who will execute them, for greater efficiency of their work and even if you feel safe, comfortable and satisfied when interacting with that space, expending less energy to this interaction. Given this context, this study aims to structure a software with the results obtained in the field, from anthropometric measure to subsidize the furniture industry in manufacturing of furniture, definition work situations, considering the different anthropometric measurements made between 2001 and 2010, using data from this sample of adults aged 18 to 65 years old and children between 6 and 11 years old. It was convenient to make the software with a site, only instead of staying on the Web has been recorded on CD Rom. Tests with the prototype allow navigation through the structure of the software. The data needed to implement the remaining modules were also raised. Issues related to system layout and usability of the interface also were not considered, because it is an initial prototype. PMID- 22317346 TI - Sizing up Australia: toward a national sizing survey. AB - This paper reports on the outcomes of research on the use of anthropometric data by designers of Australian workplaces and products used in Australian workplaces. Australian designers were asked how they used anthropometric data, and about the adequacy of data that were available to them for their needs as designers. In addition to a review of published and grey literature, designers were surveyed and asked for detailed information about their use of anthropometric data and about their needs. Thirty-two completed questionnaires were received. Two focus groups of designers were conducted; 13 people attended in Adelaide and 16 in Melbourne. The data indicated that designers either did not use anthropometric data at all or had difficulty finding data that were reliable and relevant to their specific needs. In response to the findings the Human Factors and Ergonomics Society of Australia developed a Special Interest Group for anthropometry that currently has over 150 members. The Group is actively lobbying government for an Australian Sizing Survey, so this research is an important stimulus to a major policy investment for Australia. PMID- 22317347 TI - How does the size and shape of local populations in China compare to general anthropometric surveys currently used for product design? AB - Anthropometry has long been used for a range of ergonomic applications & product design. Although products are often designed for specific cohorts, anthropometric data are typically sourced from large scale surveys representative of the general population. Additionally, few data are available for emerging markets like China and India. This study measured 80 Chinese males that were representative of a specific cohort targeted for the design of a new product. Thirteen anthropometric measurements were recorded and compared to two large databases that represented a general population, a Chinese database and a Western database. Substantial differences were identified between the Chinese males measured in this study and both databases. The subjects were substantially taller, heavier and broader than subjects in the older Chinese database. However, they were still substantially smaller, lighter and thinner than Western males. Data from current Western anthropometric surveys are unlikely to accurately represent the target population for product designers and manufacturers in emerging markets like China. PMID- 22317348 TI - Anthropometric analysis of wheelchair users: methodological factors which influence interpopulational comparison. AB - This study identified the factors existing in the methods and techniques used in the anthropometric analysis of wheelchair users which may adversely affect inter population comparisons. Five studies of anthropometric analysis of wheelchair users were examined: Nowak (1996), Jarosz (1996), Das and Kozey (1999), Kozey and Das (2004) and Paquet and Feathers (2004). All the selected studies presented intra- and inter-population data. After having identified the methods and techniques cited, a comparison was made between the procedures used by these authors and those adopted by Barros (2007). The results indicate that inter population comparison is valid only when there is similarity between the procedures and techniques used to collect data and the functional characteristics of the people evaluated. PMID- 22317349 TI - Computer re-sampling for demographically representative user populations in anthropometry: a case of doorway and clear floor space widths. AB - Anthropometric studies typically require a large number of individuals that are selected in a manner so that demographic characteristics that impact body size and function are proportionally representative of a user population. This sampling approach does not allow for an efficient characterization of the distribution of body sizes and functions of sub-groups within a population and the demographic characteristics of user populations can often change with time, limiting the application of the anthropometric data in design. The objective of this study is to demonstrate how demographically representative user populations can be developed from samples that are not proportionally representative in order to improve the application of anthropometric data in design. An engineering anthropometry problem of door width and clear floor space width is used to illustrate the value of the approach. PMID- 22317350 TI - The ergonomic and legal aspects of the heritage of the state of Pernambuco- Brazil. AB - This paper aims to demonstrate the situation of the buildings declared a historical landmark by the government spheres in the state of Pernambuco, and how they attend the norms of accessibility for those with special needs. The methodology of the research contemplated a sample of 46 heritage buildings, approximately 16% of the universe of properties, which are around 268. In turn, these were limited to Recife's Metropolitan Region Area - RMR comprising 30% of the 153 properties of the municipalities of: Cabo de Santo Agostinho, Igarassu, Itamaraca, Ipojuca, Jaboatao dos Guararapes, Moreno, Olinda, Paulista, Recife and Sao Lourenco da Mata. From the specific forms set up based on the theoretical reference, as well as graphics and photographic records were assessed the aspects of both internal and external accessibility, displacement, (visual) orientation, and the use of space and equipment. In the analysis of different types was assembled a summary table ranking the samples in accessible, partially accessible and not accessible. As general results were found that from the 46 properties examined, 2 (5%) are accessible, 16 (35%) are partially accessible and 28(60%) are not accessible. Such data, although sample, shows that the majority of heritage properties does not provide access to people physically disabled or with reduced mobility signaling for professionals, managers and society institutions on the need to reduce physical barriers in such heritage. PMID- 22317351 TI - Communication of Ergonomics in building and construction. AB - For the coming years SWEA is planning for communication and information actions. One of the sectors concerned is the building and construction industry. Focus of the information is to avoid accidents and injuries, and how companies by themselves can prevent risks. The objective of the information is to increase awareness among all stakeholders in order to secure that they are willing and able to reduce risks for workers. At the conference two brochures will be presented. They are designed to provide information and knowledge about specific risks of occupational accidents and occupational diseases which occur frequently during construction work and how they can be prevented. They are directed to all those who are involved in the construction process at different stages and who are subject to SWEAs rules and regulations. New identified risk groups are e.g. students, apprentices, self-employed, and foreign workers temporarily working in Sweden. We also see that work is still being carried out in narrow installation spaces during erection stage of buildings because the people responsible for the drawings do not take notice of the need for sufficient space to do the work. SWEA experienced that it is difficult to reach all the groups concerned with the message about how to avoid injuries and unnecessary musculoskeletal disorders. PMID- 22317352 TI - From usability requirement to technical specifications for hand-held tools and materials: an applied research in the construction field. AB - Literature shows incidence of musculoskeletal disorders in bricklaying workers as well as the relevance of good designed hand-held tools in musculoskeletal disorders prevention. In this framework, it can be supposed that providing usable hand-held tools and material in construction worksites will help to improve bricklayers' working conditions. Here a study is presented aimed at framing a methodology for usability assessment of bricklayers handled objects, in order to provide employers with practical indicators for choosing tools and materials best fitting workers needs, under the effectiveness, efficiency and satisfaction perspective. On the basis of a task analysis, usability requirements for bricklaying hand-held tools and materials have been detailed and related, quantitative and qualitative, technical specifications have been elicited. Theoretical framework and usability assessment methodology are presented and, finally, findings from a field application are discussed. PMID- 22317353 TI - Accessibility in the Fortress of Sao Jose da Ponta Grossa - Brazil. AB - This paper summarizes a study of the accessibility conditions held in the Fortress of Sao Jose da Ponta Grossa (Florianopolis, SC, Brazil), in early 2010, where the goals were analyze the components of accessibility and identify possible solutions to the problems found there. Were used several methods, that complement one with others, to confirm the need for interventions in the fortress and helps the identification of barriers and to making recommendations. PMID- 22317354 TI - Analysis of accessibility for buildings of a graduation school--an experiment in ergonomics training curriculum. AB - This article presents a description of a study experience developed in the Discipline of Supervised Internship of the Industrial Design Course of the Federal University of Paraiba. The study is based on focused on ergonomics analysis and accessibility as an object of study, access into and out of buildings of classrooms and laboratories of the same institution. Among the buildings selected, which encompass where the course is established, is a contemporary building and a renovated building of historical and artistic values for current use. The study is characterized by a description of the objects of study, analysis of the reference literature and recommendations for adjustments in the event of any inconsistency with the accessibility standards. The experience of this supervised training provided an opportunity to perform design activities to a group of students in applied ergonomics, as well as enabling contact with professional practice, adding the contact with the appropriate guidelines governing intervention in historic heritage buildings. PMID- 22317355 TI - Organizational factors related to occupational accidents in construction. AB - The purpose of this paper is to understand the influence of organizational factors on occupational accident causation. A field study was undertaken and focused on the phase of concreting the floors of a residential block in a building project in Brazil. The methodological approach was based on the analysis of carpenters' work practices and of the workers' accounts of minor falls. Observations were noted on work practices over this stage. Furthermore, interviews were conducted with the workers hired by the subcontractors and with professionals working for the main contractor. The results show that falls were related to the introduction of new building technology and its use by the workforce. The production planning and organization of activities by the subcontracted firms also led to temporary demands that were additional determining factors for falls on site. The work analysis reveals the need to consider organizational factors in prevention practices. PMID- 22317356 TI - Young workers in the construction industry and initial OSH-training when entering work life. AB - Studies have found that young workers are at risk for injuries. The risk for accidents is high within construction, indicating that young workers may be especially vulnerable in this industry. In Norway, it is possible to enter the construction industry as a full time worker at the age of 18. The aim of this paper was to explore how young construction workers are received at their workplace with regards to OHS-training. The study was designed as a qualitative case study. Each case consisted of a young worker or apprentice (< 25 years), a colleague, the immediate superior, the OHS manager, and a safety representative in the company. The interviews were recorded and analyzed through content analysis. The results showed that there were differences between large and small companies, where large companies had more formalized routines and systems for receiving and training young workers. These routines were however more dependent on requirements set by legislators and contractors more than by company size, since the legislation has different requirements with impact on OHS. PMID- 22317357 TI - Overview of ergonomics built environment. AB - This article provides an overview of academic research in the scientific discipline of ergonomics in the context of the built environment, from data collected from journals, conferences and research groups whose focus is the theme of the Ergonomics of Built Environment. Starting from the context of the Ergonomics of Built Environment, it identifies the broadcast media who publish work in this area and its scientific production, seeking to recover from the first published papers to the production of the most recent scientific journals and conferences to be launched 2010. From this mapping, we identified the major outstanding and open issues in these studies, outlining the state of the art Ergonomics Built Environment, in order to inform those interested and intend to develop scientific research in this field. PMID- 22317358 TI - Methodological proceedings to evaluate the physical accessibility in urban historic sites. AB - Historic urban sites are set by cultural and social diversities, generating multiple activities and use and access to these sites should be available to all people including those with disabilities. Taking into consideration that using the same methodology that was used in different historic sites researches with positive results facilitates replication, we aimed to develop methodological procedures that identify conditions of physical accessibility in open public spaces and access to public buildings in historic urban sites to support proposals about design requirements for improvements to the problems diagnosed and control inadequacies of the physical environment. The study methods and techniques from different areas of knowledge culminated in a proposal built with an emphasis on user participation that could be applied with low cost and in relatively short period of time. PMID- 22317359 TI - Risk management project for work with precast concrete shells. AB - This paper describes a project with the aim of reducing the risk of injury when using precast concrete shells in the Swedish construction industry by identifying injury risks, developing and implementing solutions. An interactive research approach was used. Three major injury risks were identified and a system consisting of three tools and a handbook was developed, evaluated, and implemented at one company and made available to the construction industry. PMID- 22317360 TI - The elderly in the shopping centers: the usability study of semipublic spaces as attractiveness generator. AB - This article aims to study the importance of the attributes of usability and attractiveness for the semi-public spaces of Shopping Centers considering the elderly users, the psycho-cognitive and bio-physiological changes resulting from the aging process, as well as their expectations of the built space. Through a qualitative study of theoretical review with a multidisciplinary focus in architecture, ergonomics, gerontology, environmental psychology and management, the conditions of the elderly users were identified, and also the attributes related to usability and attractiveness, collected in order to understand and organize their interrelationships, to suggest recommendations about the drafting of Shopping Centers, aiming to generate projects and environments that should promote the efficient and satisfactory use for elderly and may also create a competitive advantage for these enterprises. PMID- 22317361 TI - Does team lifting increase the variability in peak lumbar compression in ironworkers? AB - Ironworkers frequently perform heavy lifting tasks in teams of two or four workers. Team lifting could potentially lead to a higher variation in peak lumbar compression forces than lifts performed by one worker, resulting in higher maximal peak lumbar compression forces. This study compared single-worker lifts (25-kg, iron bar) to two-worker lifts (50-kg, two iron bars) and to four-worker lifts (100-kg, iron lattice). Inverse dynamics was used to calculate peak lumbar compression forces. To assess the variability in peak lumbar loading, all three lifting tasks were performed six times. Results showed that the variability in peak lumbar loading was somewhat higher in the team lifts compared to the single worker lifts. However, despite this increased variability, team lifts did not result in larger maximum peak lumbar compression forces. Therefore, it was concluded that, from a biomechanical point of view, team lifting does not result in an additional risk for low back complaints in ironworkers. PMID- 22317362 TI - Acessibility in collective housing for the elderly: a case study in Portugal. AB - Physical spaces need to be adjusted to suit the changes of a physical, cognitive and emotional order occasioned by the natural aging of people. Ergonomics of the built environment contributes to improving the interaction of the user and physical environment, with a view to their comfort and safety. By thinking through the influence that environments have on the quality of life of the elderly, this article presents an assessment of accessibility in private units- bedrooms and bathrooms--of a Long-Stay Institution for the Elderly (ILPI in Portuguese) in Portugal. The analysis of the physical and spatial conditioning factors by means of the Ergonomics Methodology for the Built Environment (EMBE), proposed by VILLAROUCO (2008), gave evidence of the need for interventions to suitably adapt physical infrastructure, with the objective of promoting the physical well-being of the elderly, and thus, enhancing the autonomy and independence of a wider range of users. PMID- 22317363 TI - Impact of lightweight and conventional jackhammers on the operator. AB - Jackhammer manufacturers have recently developed lightweight (45-60 lbs) jackhammers intended to reduce the required lifting and pushing forces during operation. However, the vibration characteristics of the lightweight jackhammers and their effect on muscle activity are currently unknown. The objective of this study was to compare the measured vibration and muscle activity between: (i) conventional (90 lb) and light weight (60 lb) jackhammers, (ii) different pavement type/thickness combinations, and (iii) pneumatic and hydraulic jackhammers. Five jackhammers were tested on 4 and 6 inch thick asphalt and concrete pavements by four experienced operators. Analysis of the results revealed that both weight classes averaged 9.7 m/s(2) at the 20 Hz weighted 1/3 octave band frequency, and the TLV of daily exposure for either weight class of jackhammer was less than 1.5 hours/per day. There was an approximately 33% difference in vibration measured on the hand of the operators due to pavement thickness, 30% due pavement type, and no difference due to power source. Conventional jackhammers overall produced higher muscle activity than lightweight jackhammers. Although selection of the correct jackhammer for the job involves many factors including pavement type and thickness, the results of this research can be used to assist in selecting the appropriate jackhammer. PMID- 22317364 TI - Naturalistic observation of drivers' interactions while overtaking on an undivided road. AB - Current models of driving behavior and designs of driver support systems are not taking adequately into account the interactions between drivers. Although a driver's intended maneuver may not be physically possible at a specific time point, it may still be safely executed if the driver's intention is successfully communicated to and interpreted by another driver, who alters the own future trajectory so as to enable the maneuver execution. This paper presents some empirical findings relevant to communicative and cooperative interactions between drivers along naturalistic overtaking maneuvers on an undivided road. The cues used by drivers to interpret other drivers' intention and the drivers' interactions were extracted through video observations of the maneuvers together with the frequency of such interactions per level of traffic risk. The findings show that drivers use formal and informal cues to anticipate other drivers' intention. A significant percentage of maneuvers were performed after facilitation by other drivers. Future studies should focus on this phenomenon while future models of driving behavior should incorporate communicative and cooperative interactions among drivers, so as to design adequate cooperative support systems to enhance road safety. PMID- 22317365 TI - Comparison of two human-machine-interfaces for cooperative maneuver-based driving. AB - In the project "Conduct-by-Wire" which is founded by the German Research Foundation (DFG) cooperative maneuver based driving is examined. In this paper two different input devices (gesture recognition and tactile touch display) are compared in a simulator study with 29 participants. It shows that the major advantage of the gesture recognition is that there is no need for the driver to take his gaze off the road. In contrast, the number of gazes at the tactile touch display is significantly higher. The major advantage of the tactile touch display is that no input errors occurred during the test drives. Conversely, the gesture recognition was significantly worse. Nevertheless, further work is needed to decide which input device is the best. PMID- 22317366 TI - Safety implications of infotainment system use in naturalistic driving. AB - The use of a radio while driving has long been considered a "threshold" of distraction that is socially acceptable although it may be a factor in some crashes and near crashes. This "social acceptance" has prompted the use of radio tasks, specifically radio tuning, as "references" that should not be exceeded by other secondary and tertiary tasks that make their way into the vehicle. As new functions make their way into vehicle radios (or more advanced infotainment systems), however, it is possible that radio tasks may become distracting to a level that surpasses current driver expectations. This investigation examines the naturalistic usage of several advanced infotainment systems and examines whether usage is associated first with changes in near crash occurrence and second with changes in driving behavior. Little association was found with near crashes: 5 of 46 near crash events observed in the dataset exhibited infotainment system use. Drivers involved in infotainment system use during near crashes, however, did exhibit distinct glance behaviors, generally suggesting lower levels of awareness about their driving environment. Initial analyses of a larger dataset appear to confirm these findings. PMID- 22317367 TI - Using naturalistic driving films as a design tool for investigating driver requirements in HMI design for ADAS. AB - In recent years, there are many naturalistic driving projects have been conducted, such as the 100-Car Project (Naturalistic Driving study in United State), EuroFOT(European Large-Scale Field Operational Tests on Vehicle Systems), SeMi- FOT(Sweden Michigan Naturalistic Field Operational Test and etc. However, those valuable naturalistic driving data hasn't been applied into Human-machine Interaction (HMI) design for Advanced Driver Assistance Systems (ADAS), a good HMI design for ADAS requires a deep understanding of drive environment and the interactions between the driving car and other road users in different situations. The results demonstrated the benefits of using naturalistic driving films as a mean for enhancing focus group discussion for better understanding driver's needs and traffic environment constraints. It provided an efficient tool for designers to have inside knowledge about drive and the needs for information presentation; The recommendations for how to apply this method is discussed in the paper. PMID- 22317368 TI - A method to investigate drivers' acceptance of Blind Spot Detection System(r). AB - Lately, with the goal of improving road safety, car makers developed and commercialised some Advanced Driver Assistance Systems (ADAS) which, through the detection of blind spot areas on the vehicle's sides, could help the drivers during the overtaking and the change lane task. Despite the possible benefits to reduce lateral crashes, the overall impact on road safety of such systems have not been deeply studied yet; notably, despite some researches have been carried out, there is a lack of studies regarding the long-term usage and drivers' acceptance of those systems. In order to fill the research gap, a methodology, based on the combination of focus groups interviews, questionnaires and a small scale field operational test (FOT), has been designed in this study; such a methodology aims at evaluating drivers' acceptance of Blind Spot Information System(r) and at proposing some ideas to improve the usability and user friendliness of this (or similar) device in their future development. PMID- 22317369 TI - A comprehensive literature review of the pelvis and the lower extremity FE human models under quasi-static conditions. AB - Finite Element Modeling (FEM) has become a vital tool in the automotive design and development processes. FEM of the human body is a technique capable of estimating parameters that are difficult to measure in experimental studies with the human body segments being modeled as complex and dynamic entities. Several studies have been dedicated to attain close-to-real FEMs of the human body (Pankoke and Siefert 2007; Amann, Huschenbeth et al. 2009; ESI 2010). The aim of this paper is to identify and appraise the state-of-the art models of the human body which incorporate detailed pelvis and/or lower extremity models. Six databases and search engines were used to obtain literature, and the search was limited to studies published in English since 2000. The initial search results identified 636 pelvis-related papers, 834 buttocks-related papers, 505 thigh related papers, 927 femur-related papers, 2039 knee-related papers, 655 shank related papers, 292 tibia-related papers, 110 fibula-related papers, 644 ankle related papers, and 5660 foot-related papers. A refined search returned 100 pelvis-related papers, 45 buttocks-related papers, 65 thigh-related papers, 162 femur-related papers, 195 knee-related papers, 37 shank-related papers, 80 tibia related papers, 30 fibula-related papers and 102 ankle-related papers and 246 foot-related papers. The refined literature list was further restricted by appraisal against a modified LOW appraisal criteria. Studies with unclear methodologies, with a focus on populations with pathology or with sport related dynamic motion modeling were excluded. The final literature list included fifteen models and each was assessed against the percentile the model represents, the gender the model was based on, the human body segment/segments included in the model, the sample size used to develop the model, the source of geometric/anthropometric values used to develop the model, the posture the model represents and the finite element solver used for the model. The results of this literature review provide indication of bias in the available models towards 50th percentile male modeling with a notable concentration on the pelvis, femur and buttocks segments. PMID- 22317370 TI - Keeping rail on track: preliminary findings on safety culture in Australian rail. AB - 'Safety culture' is identified in the literature as a critical element of healthy and safe workplaces. How can rail organizations ensure that consistently effective work health and safety cultures are maintained across the diversity of their operations? This paper reports on research that is currently underway in the Australian rail industry aimed at producing a Model of Best Practice in Safety Culture for the industry. Located in rail organizations dedicated to the mining industry as well as urban rail and national freight operations, the research examines the constructs of organizational culture that impact on the development and maintenance of healthy and safe workplaces. The research uses a multi-method approach incorporating quantitative (survey) and qualitative (focus groups, interviews and document analysis) methods along with a participative process to identify interventions to improve the organization and develop plans for their implementation. The research uses as its analytical framework the 10 Platinum Rules, from the findings of earlier research in the New South Wales (Australia) mining industry, Digging Deeper. Data collection is underway at the time of writing and preliminary findings are presented at this stage. The research method may be adapted for use as a form of organizational review of safety and health in organizational culture. PMID- 22317371 TI - Understanding human factors in rail engineering: re-analysis of detailed, qualitative data on functions and risks. AB - The paper reports on the review and re-analysis of information that has been collected in earlier field studies on the functions and associated risks in rail engineering and maintenance. Two methods of Cognitive Work Analysis have been adapted and used to identify and represent important components of the rail engineering system and the situations in which activities occur. Additional classification exercises have been used to determine issues of strategic importance to the organisation, related to the functions and human factors risks in performing these functions. The effectiveness of the methods in this industrial context has been evaluated. Conclusions are drawn on how this type of approach can be used to produce relevant findings on the following: What the organisation knows about roles, functions and descriptions of tasks that are relevant for engineering and maintenance work; (2) the HF risks for today's (and unless things change), tomorrow's railway; (3) how this knowledge can help in determining organisational priorities for future work. PMID- 22317372 TI - Indonesian railway accidents--utilizing Human Factors Analysis and Classification System in determining potential contributing factors. AB - The prevalence of Indonesian railway accidents has not been declining, with hundreds of fatalities reported in the past decade. As an effort to help the National Transportation Safety Committee (NTSC), this study was conducted that aimed at understanding factors that might have contributed to the accidents. Human Factors Analysis and Classification System (HFACS) was utilized for this purpose. A total of nine accident reports (provided by the Indonesian NTSC) involving fatalities were studied using the technique. Results of this study indicated 72 factors that were closely related to the accidents. Of these, roughly 22% were considered as operator acts while about 39% were related to preconditions for operator acts. Supervisory represented 14% of the factors, and the remaining (about 25%) were associated with organizational factors. It was concluded that, while train drivers indeed played an important role in the accidents, interventions solely directed toward train drivers may not be adequate. A more comprehensive approach in minimizing the accidents should be conducted that addresses all the four aspects of HFACS. PMID- 22317373 TI - Designing dynamic distributed cooperative Human-Machine Systems. AB - The paper presents a new approach to the development of cooperative human-machine systems in the Transportation domain which is currently researched in the European project D3CoS. A necessary precondition for the acceptance of cooperative human-machine systems with shared control is the confidence and trust of the user into the system. D3CoS tackles this important issue by addressing the cooperative system as the object and the target of the system development process. This new perspective, along with corresponding innovative methods, techniques and tools, shall allow the identification of optimal task and authority sharing approaches supported by intuitive human-machine interaction and user interfaces at an early stage of system development. This will support powerful teamwork between humans and machines or between machines and machines that is transparent, intuitive and easy to understand. The paper describes the research dimensions for the development of the methods, techniques and tools as well as first results. PMID- 22317374 TI - User acceptance of cooperative maneuver-based driving--a summary of three studies. AB - Modern cars offer drivers support with the help of a number of driver assistance systems. Those systems aim to relieve drivers through assumption of sub parts of the driving task (e.g. in case of an Adaptive Cruise Control by regulation of vehicle speed and time gap to preceding vehicle). Today, systems are controlled and monitored separately which leads to efforts to combine the functionality of all systems in an overlying assistance for drivers. The approach of the University of Technology Darmstadt is called Conduct-by-Wire and can be seen as a cooperative maneuver-based driving paradigm, where the driver gives maneuver command to the systems which are automatically executed. This paper summarizes the results of three studies which investigated the user acceptance of this driving paradigm. Overall, it can be said that the acceptance of the system depends on personal traits of the driver and on the driving situation. Almost all participants are willing to use Conduct-by- Wire for routine tasks such as commuting, which makes the systems interesting for company cars. Still, there remain a number of drivers who are not willing to use such a highly automated system at all. PMID- 22317375 TI - How shall we design the future vehicle for Chinese market. AB - Surface transportation system is developing very fast in China and the number of vehicles is increasing quickly as well. This development creates a lot of problems on traffic safety and the number of accident is also increasing. In this paper, we made deep analysis of different possible causes of safety problems through three aspects: the traffic environment and infrastructure, in-vehicle information system design and the characteristics of drivers. There are many factors in each aspects may contribute to the transportation safety problems. Problems with infrastructure design and traffic design contribute over 50% of the traffic accident. Another important factor is that people has very little traffic safety concept and very weak on understanding the important of right behavior on the road. This paper has pointed the urgent needs to study the human factors in road and transportation system and vehicle HMI design, as there are very few such studies available in literature based on Chinese situation. The paper also proposed the needs to develop proactive educational system that can promote driver's understanding of traffic safety and to take the right action during drive. PMID- 22317376 TI - DriveID: safety innovation through individuation. AB - The driving task is highly complex and places considerable perceptual, physical and cognitive demands on the driver. As driving is fundamentally an information processing activity, distracted or impaired drivers have diminished safety margins compared with non- distracted drivers (Hancock and Parasuraman, 1992; TRB 1998 a & b). This competition for sensory and decision making capacities can lead to failures that cost lives. Some groups, teens and elderly drivers for example, have patterns of systematically poor perceptual, physical and cognitive performance while driving. Although there are technologies developed to aid these different drivers, these systems are often misused and underutilized. The DriveID project aims to design and develop a passive, automated face identification system capable of robustly identifying the driver of the vehicle, retrieve a stored profile, and intelligently prescribing specific accident prevention systems and driving environment customizations. PMID- 22317377 TI - Assisted entry mitigates text messaging-based driving detriment. AB - Previous research using cell phones indicates that manual manipulation is not a principal component of text messaging relating driving detriment. This paper suggests that manipulation of a phone in conjunction with the cognitive need to compose the message itself co-act to contribute to driving degradation. This being so, drivers sending text messages might experience reduced interference to the driving task if the text messaging itself were assisted through the predictive T9 system. We evaluated undergraduate drivers in a simulator who drove and texted using either Assisted Text entry, via Nokia's T9 system, or unassisted entry via the multitap interface. Results supported the superiority of the T9 system over the multitap system implying that specific assistive technologies can modulate the degradation of capacity which texting tragically induces. PMID- 22317378 TI - Effects of extended work shifts on employee fatigue, health, satisfaction, work/family balance, and patient safety. AB - 12-hour shifts are quickly spreading in Europe. From our multivariate analysis concerning 25,924 European nurses, including twenty explanatory variables simultaneously, we found that work schedule itself is not a major determinant factor. Nurses aim to choose or accept night shifts or 12-hour shift in order to reduce their work/home conflicts, however, at the expense of the patient's safety, as well as their own health and safety. Therefore, it is important to develop measures, such as extended child care, association of nurses to the elaboration of their rota, 9- or 10-hour shifts in the afternoon, allowing naps during night shifts, and reduction of changing shifts with short notice. Work schedules must be organized in order to allow time for shift handover, social support and team building. PMID- 22317379 TI - When gender bumps into health and safety training: working conditions, readings and challenges drawn from a case study in an industrial chemicals company. AB - Health, safety and environmental issues are at present a social concern and an increasingly referred topic in the so called gender studies. This paper focuses on the relations between training, gender and risk perception in an industrial chemicals company, in Portugal, characterized by a mainly male population and by the presence of high occupational and environmental hazards. After characterizing the company and the training project that started up this reflection, the paper presents the reasons for its focus on gender followed by the essential methodological explanations: 14 interviews were made with male and female workers from the company; their content was transcribed from the audio recordings and it was systematically analyzed. A gender-attentive socio demographic analysis was also undertaken. Although at the beginning the company did not consider the gender issues as a problem nor was it the central topic of the training, which focused on the prevention of occupational and environmental hazards, the results reveal that the gender factor brought to light some working conditions, which so far have not been properly discussed within the group meetings. As a consequence, there is now room for the transformation of the representations on those working conditions. PMID- 22317380 TI - Thinking about gender, thinking about a common space of observation and discussion of the work activity of the other: the case of bus drivers. AB - The work activity of urban bus drivers is held in the public space and characterized by a constant vigilance, but the moments of observation the colleagues' work are scarce. This fact results in a paradox--it is a work activity that is more visible to "outsiders" than to "insiders"--which has an important impact on the debate of the work activity from a perspective of gender and the women's work in a predominantly male context. Ergonomic analysis of work and semi-structured interviews were conducted with 32 urban public transport drivers, 16 women and 16 men. The results reveal the lack of conditions for the drivers' knowledge of the activity of another, especially when that other is a woman--while men attribute characteristics to women based on gender stereotypes and an extension of their role in the private sphere, women relate them with the need to prove their competence and be recognized. It is proposed the development, in the context of training, of a space for debate and knowledge of the activity of the other and for the creation of conditions for another integration of women in the profession and for another visibility of their work. PMID- 22317382 TI - Women's working conditions in hospital cleaning: a case study. AB - Hospital cleaning work, as health care work, is mainly performed by women all over Europe. Hospital cleaning activities represent a poorly studied sector although very important also for patient's health. We applied the Method of Organizational Congruencies to study cleaning work in three typical hospital units (Emergency Room, Haematology, General Medicine) of a roman University hospital where 198 women cleaners work. We analyzed the 731 technical actions performed in the three shifts and the related Organizational Constraints (OC). Working outsourcing, no occupational risks training, washing personal equipment at home, standing, long walking, early morning and night shift in emergency room, high monotony (>10 actions per hour) contact with biological and chemicals materials, risk conditions of accidents, artificial lights, hot microclimate and working in a cure setting represent the main Organizational Constraints. Differences among the three Units are discussed together with the importance of considering cleaning hospital as a preventive action towards hospital clinical risk. PMID- 22317381 TI - Shift work--problems and its impact on female nurses in Udaipur, Rajasthan India. AB - Abstract : There is good evidence that shift work has negative effects on workers health, safety and performance. It is quite appropriate that attention is paid to this very important feature of socio-technical systems, which may adversely affect mental and physical health, social life and safety of shift workers. Research into the impact of shift work on professionals has consistently identified a range of negative outcomes in physical, psychological, and social domains (Akerstedt, 1988; Costa, Lievore, Casaletti, Gaffuri, & Folkard, 1989; Kogi, 2005; Paley & Tepas, 1994). Hospitals, the biggest employer in the health care field, employ more night shift workers than any other industry. It can therefore be inferred that in medical domain high percentage of workforce may be affected by problems related to shift work. Thus the present study will provide knowledge base for the problems faced by the female nurses. The present study was undertaken with an objective of getting an insight into the problems faced by female nurses in shift work. . It was found that the female nurses in India worked on roaster pattern of change in shift every seven days. They did not have a say in the change of duties, it could only be done on mutual grounds. Partners of younger group did not much adjust to their shift pattern this created stress among the nurses.The results showed that the female nurses in both the age groups i.e. 30-45 years and 45-60 years faced many problems related to health and well being, fatigue, social and domestic situations. They could not give much time to their children in particular. Travelling in nights was risky for them. Common problem was the insufficient sleep during night shifts. The nurses had to cater to the needs of the family, children in particular along with the adjustments to be made due to shift work. They had to sometimes do the night duties and attend social functions as a part of their duty. Children and husband in some cases did not cooperate this lead to frustration. When asked as to whether they would could shift job if they get regular one more than 50 % said yes this means that there need to be come training and intervention for the shift workers and their family so that the problems faced and their impact on personal health of the female nurses could be reduced. PMID- 22317383 TI - Gender differences on the job satisfaction in the phase of implementing advanced manufacturing technology in the Chinese manufacturing firms. AB - This research gave an effort to study on gender differences in the job satisfaction for technological innovation at Chinese manufacturing firm. The exploratory study was conducted in four Chinese furniture manufacturing firms, which are all in the phases of introducing advanced manufacturing system. The results of statistical analysis show that general satisfaction of female employees to their jobs is significantly higher than male employees. In addition, supervisory satisfaction of female employees is significantly higher than male employees. The findings of the study reveal that activities are suggested to be carried out to increase the job satisfaction of male employees, especially improve communication and relationship between the managerial and the non managerial levels in the innovation process. In addition, the higher job satisfaction of female employees could be considered a positive factor for the successful implementation of AMT in the technological innovation, although male employees are still dominated work force in the case study firms. PMID- 22317384 TI - Influence of gender on the prevalence of Rsi/WRULD in meat-packing plants. AB - This research aimed to determine the handgrip strength difference between (?) and (?) and its influence on the incidence of RSI / WRULD in meat-packing plants. The study had the participation of 201 workers from the bone sector of a pig slaughterhouse located in the municipality of Sao Miguel do Iguacu, state of Parana, Brazil, being 98 men and 103 women with mean age of 34.3 ( +/- 4.7 years) and weight of 66.3 (+/- 6.5 kg) for (?) and 36.5 (+/- 6.4 years) and weight of 77.6 (+/- 5.8 kg) for (?). Handgrip strength was used in the evaluation. Descriptive statistics and "t" test were applied, with significance level of 0.05% for strength test and percentage of pain levels. The results were presented according to gender (?) 44.94 kgf (+/- 4.51) for the dominant hand (DH) and 41.09 kgf (+/- 4.09) for the non-dominant hand (NDH), and for males (?), the average was 29.20 kgf (+/- 2.20) for DH and 28.40 kgf (+/- 2.39) for NDH. Statistical analysis indicated a "t" greater than 0.05 with 3.49% for DH and 2.95 for NDH, showing that (?) and (?) have strength levels significantly different in both hands and this study indicated that females have 35% less strength in the DH and 30.8% in the NDH. With regard to pain symptoms, pain for (?) was higher than for (?), with 21.5% in the shoulder region, 25% in neck, 48% in the column, 48.7% and in the arms and 48.8% in wrists and hands. It could be concluded that (?) have less strength and higher percentage of pain in relation to (?) when exposed to repetitive work and with identical tasks. Thus, it becomes clear that to avoid RSI / WRULD in meat-packing plants, companies should use knowledge on ergonomics in order to provide a work environment that respects the physiological differences between males and females. PMID- 22317385 TI - Gender and age do not influence the ability to work. AB - Work capacity is related to physical, environmental and psychosocial factors and is influenced by individual characteristics and occupations. The aim of this study was to evaluated the relationship between work capacity, gender and age. 360 people employed at an institution of higher education of both genders and similar age were asked to participate in this study. The ability to work was analyzed using Work Ability Index (WAI). Descriptive statistical, Pearson correlations and ANOVA test was applied. Of these, 197 workers who participated in the study completed and returned the questionnaire. The results show there weren't any significant differences between work ability in relation to gender and age, but we observed an increase variability of responses for WAI score in older workers. No significant differences in the perception of the ability of work between men and women.. PMID- 22317386 TI - Gender involvement in manual material handling (mmh) tasks in agriculture and technology intervention to mitigate the resulting musculoskeletal disorders. AB - The lifting and carrying of loads in agriculture on small landholdings are unavoidable. Rural communities often lack access to appropriate technologies which may result in various health hazards. The objective was to study gender participation in agricultural activities involving manual material handling tasks, to assess MSDs experienced in various MMH tasks and to evaluate traditional method and designed technology. The study was conducted on 100 agricultural workers. Data on gender participation in MMH tasks in household, animal husbandry and agriculture and resulting MSDs was gathered. Pre and post assessment of technology intervention was done for NIOSH Lifting Index, QEC, and RPE. The results revealed greater susceptibility of females to musculoskeletal problems in most of the household and animal husbandry tasks. The hand trucks designed were pushing type with power grasp handle. The respondents were advised to carry 5 kg of weight per lift instead of lifting more weight in one lift/minute while filling the hand truck. By decreasing the weight and increasing the number of lifts per minute the respondents were seen falling in green zone indicating significant reduction in NIOSH lifting index. QEC scores concluded that for filling the hand truck 5 kg of weight should be carried to keep the exposure level low. PMID- 22317387 TI - Intervention of gender friendly land preparation technologies for drudgery reduction of hill farm women. AB - Inventory of all agricultural tasks depicted land preparation by women farmers as one of the most drudgery prone task with high energy cost, thereby, making it amenable to ergonomic interventions in terms of improved technologies (clod breaker, improved plough/'danella') to relieve women from high energy demands, time spent and associated drudgery. The study was conducted in two hill states of India viz. Himachal Pradesh (35 villages and 900 representative samples) and Uttrakhand (10 villages and 900 representative samples). Experimental data were conducted on representative sub sample of 60 hill farm women of both the states to assess physiological workload and musculo-skeletal problems both while working with traditional tools along with improved tools by employing selected parameters viz. physical fitness level, physiological parameters etc. The results showed that heart rate values were more than acceptable limits for task performed with the traditional tools as compared with improved tools. Significant reduction in the heart rate was observed while working with improved tools. Analysis of MSDs showed that the postural stress and severity of pain in various body parts was reduced by adopting new technology. Hence, the use of improved land preparation tools is recommended over the existing ones for drudgery reduction. PMID- 22317388 TI - Ergonomic interventions in weeding operations for drudgery reduction of hill farm women of India. AB - Weeding is an important time consuming and drudgery prone task mainly performed by hill farm women for almost all crops grown. This directs for interventions in terms of improved technologies (weeder, kutla and hoes) to relieve women from high energy demands, time spent and associated drudgery particularly for weeding activity. The study was conducted in two hill states of India viz. Himachal Pradesh (35 villages and 1500 representative samples) and Uttrakhand (10 villages and 500 representative samples). Experimental data were conducted on representative sub sample of 60 hill farm women of both states to assess physiological workload and musculo-skeletal problems both while working with traditional tools along with improved tools by employing selected parameters viz. physical fitness level, physiological parameters etc. The results showed that heart rate values were more than acceptable limits for task performed with the traditional tools as compared with improved tools. Significant reduction in the heart rate was observed while working with improved tools. Analysis of MSDs showed that the postural stress and severity of pain in various body parts was reduced by adopting new technology. Hence, the use of improved weeding tools is recommended over the existing ones for drudgery reduction. PMID- 22317389 TI - Migrant women farm workers in the occupational health literature. AB - Little attention has been given to the vulnerable populations of migrant women agricultural workers. A systemic review in PubMed was carried out (1990-2008) using terms related to migrant agricultural workers, with specific focus on women. Case studies from Lebanon and California are presented to highlight key physical, psychosocial, and cultural risk factors among these working populations. The review revealed a host of potential problems that span from pesticide exposure and musculoskeletal disorders to socio-cultural barriers. Comprehensive exposure-outcome and intervention studies focusing specifically on migrant women in agriculture are lacking. In depth studies focusing on the work environment of migrant women workers in the agricultural sector are needed. Personal and environmental factors that influence health should be considered in any effective intervention aiming to influence policy making and have a positive impact on these vulnerable working populations. PMID- 22317390 TI - Assessment of energy balance of Indian farm women in relation to their nutritional profile in lean and peak agricultural seasons. AB - In India, the farm women are not only involved in household activities but also contribute in various farm operations, animal husbandry. The objective was to assess nutritional profile of the farmwomen and their occupational health problems, to compare the physiological workload in lean and peak seasons and to find out relationship between physiological workload and nutritional intake. The study was conducted on a sample of 90 farmwomen. Energy Intake was calculated using physiological fuel values of carbohydrate, fat and protein. Energy Expenditure Rate (EER), Total Energy Expenditure (TEE) and Energy Balance were calculated. The physiological workload was assessed using sub-maximal workload technique. The results revealed that all the respondents of all categories were, more or less, performing all the agriculture, allied and household activities. In all the agriculture activities physiological hazards such as body pain and fatigue were dominant. Dietary, nutritional and energy intake was lower for heavy workers, from all landholding and BMI categories. HR and OCR were in linear relationship in all BMI categories. Physical work capacity increased with good nutritional status and decreased with age. Regression equations were suggested for calculating oxygen consumption (y) at their known heart rate (x) during various agriculture operations. PMID- 22317391 TI - Integration of time as a factor in ergonomic simulation. AB - The paper describes the application of a simulation based ergonomic evaluation. Within a pilot project, the algorithms of the screening method of the European Assembly Worksheet were transferred into an existing digital human model. Movement data was recorded with an especially developed hybrid Motion Capturing system. A prototype of the system was built and is currently being tested at the Volkswagen Group. First results showed the feasibility of the simulation based ergonomic evaluation with Motion Capturing. PMID- 22317392 TI - Metabolic impact of shift work. AB - In developing countries, shift work represents a considerable contingent workforce. Recently, studies have shown that overweight and obesity are more prevalent in shift workers than day workers. In addition, shift work has been associated with a higher propensity for the development of many metabolic disorders, such as insulin resistance, diabetes, dislipidemias and metabolic syndrome. Recent data have pointed that decrease of the sleep time, desynchronization of circadian rhythm and alteration of environmental aspects are the main factors related to such problems. Shortened or disturbed sleep is among the most common health-related effects of shift work. The plausible physiological and biological mechanisms are related to the activation of the autonomic nervous system, inflammation, changes in lipid and glucose metabolism, and related changes in the risk for atherosclerosis, metabolic syndrome, and type II diabetes. The present review will discuss the impact of shift work on obesity and metabolic disorders and how disruption of sleep and circadian misalignment may contribute to these metabolic dysfunctions. PMID- 22317393 TI - Ergonomic risk assessment with DesignCheck to evaluate assembly work in different phases of the vehicle development process. AB - Occupational hazards exist, if the design of the work situation is not in accordance with ergonomic design principles. At assembly lines ergonomics is applied to the design of work equipment and tasks and to work organisation. The ignoring of ergonomic principles in planning and design of assembly work leads to unfavourable working posture, action force and material handling. Disorders of the musculoskeletal system are of a common occurrence throughout Europe. Musculoskeletal disorders are a challenge against the background of disabled workers. The changes in a worker's capability have to be regarded in the conception of redesigned and new assembly lines. In this way ergonomics becomes progressively more important in planning and design of vehicles: The objective of ergonomic design in different stages of the vehicles development process is to achieve an optimal adaptation of the assembly work to workers. Hence the ergonomic screening tool "Design Check" (DC) was developed to identify ergonomic deficits in workplace layouts. The screening-tool is based on the current ergonomic state of the art in the design of physical work and relevant EU legal requirements. It was tested within a federal German research project at selected work stations at the assembly lines at Dr.-Ing. h.c. F. Porsche AG / Stuttgart. Meanwhile the application of the screening-tool DC is transferred in other parts of the Porsche AG, Stuttgart. It is also realized as an ergonomic standard method to perform assembly work in different phases of the vehicle development process. PMID- 22317394 TI - The charge of ergonomics--a model according to the influence of ergonomic workplace design for economical and efficient indicators of the automotive industry. AB - The importance of ergonomic workplace design has been rising incredibly. The knowledge of the interaction with a view to many indicators (e.g. operators' health, quality, productivity etc.) in the automotive assembly shop pushed into another thinking of ergonomics and an increasing awareness of economic possibilities relating to benefits and cost savings aligned with ergonomics. The paper discusses exemplary the various indicators and factors which could be influenced by ergonomic workplace design. These factors are linked each other and support the statement of ergonomic efficiency. Thus, the aim of this paper is to present a model which describes that investments in ergonomic work placement acts with preventive measurements, minimization of losses (refinishing operations, compensation money etc.) and extensive economies on the whole company. PMID- 22317395 TI - Assessing driver's mental representation of Adaptive Cruise Control (ACC) and its possible effects on behavioural adaptations. AB - The introduction of Adaptive Cruise Control (ACC) could be very helpful for making the longitudinal driving task more comfortable for the drivers and, as a consequence, it could have a global beneficial effect on road safety. However, before or during the usage of the device, due to several reasons, drivers might generate in their mind incomplete or flawed mental representations about the fundamental operation principles of ACC; hence, the resulting usage of the device might be improper, negatively affecting the human-machine interaction and cooperation and, in some cases, leading to negative behavioural adaptations to the system that might neutralise the desirable positive effects on road safety. Within this context, this paper will introduce the methodology which has been developed in order to analyse in detail the topic and foresee, in the future, adequate actions for the recovery of inaccurate mental representations of the system. PMID- 22317396 TI - Managing ergonomics in the development of rotation between workstations in the automotive industry. A balance between health and traceability of tasks. AB - Abstract When the subject rotation between workstations (job rotation) is inside the organizations it's seemed that technically there are lots of restrictions to the development of an adequate system of rotation. We went from the need for an advanced ergonomic study and even possible restrictions of versatility and training of employees. The implementation of the ideal system of rotation passes through stages of development and research ergonomic study of the level of employee versatility, awareness and discussion with employees, implementation of the proposed system, feedback and audits for maintenance of the ideal sequence and time of rotation. For the success of the project there is a need for multidisciplinary involvement in the areas of manufacturing engineering, industrial engineering, human resources, medical services and manufacturing. Rotation between the tasks may mean that a worker should conduct two or more different activities in different parts of the day (ie. change between activity A and activity B "between 1 hours and 2 hours interval). An important consideration is to ensure that different activities do not present the same ergonomic risk for the same body part. The tracing of the execution of the activity is an important factor for production processes. Thus it is possible to conduct appropriate levels of training for employees and ensure safe and sustainable processes in terms of workers' health, productivity and quality. PMID- 22317397 TI - Prevention of MSD by means of ergonomic risk assessment (tools) in all phases of the vehicle development process. AB - In industrialized countries musculoskeletal disorders (MSD) play an import role and are often responsible for almost one third of the total sick leave. The changes in the demographic profiles, i.e. aging work forces might even worsen this situation in the future. For a highly productive and sustainable use of human resources in production systems, ergonomics offers high potentials. In the recent years the authors have developed several ergonomic risk assessment tools, especially for the use in automotive industries. These methods may be used during the planning phases in the Tech Centers as well as during the production phase at shop floor level. The tools might also be used for a standardized communication in between the Tech Center and the plants to improve the effects of "lessons learned" for the design and layout of workstations and processes and the optimization of vehicle components. This paper describes suitable risk assessment tools as well as the integration of these tools into the vehicle development process. It introduces a comprehensive management approach for the integration of ergonomics into the management of production systems. PMID- 22317398 TI - Global ergonomics strategy in Volkswagen: from the product construction, over the planning until the serial process. AB - The Volkswagen Group operates and coordinates the activities of ergonomics from Wolfsburg in Germany and works with its contact persons of every plant and brand of the group towards an integrated proceeding relating to ergonomics. For the ergonomic process it is very important to consider the ergonomics in the whole production process, still from the beginning the conception and construction of the vehicle in the early phases. In these phases there is a big potential to work in the preventive ergonomics and avoid correcting the workstations after start of production. Therefore, it is important to have fluently information in all this phases and identify the potential in each of them. In order to attend these items, Volkswagen has defined different activity fields: coordination of ergonomic standards and the roll-out into all the plants, introducing the ergonomic items in the product development process (PEP), considering the constant improvement of the workplaces in the Volkswagen-Way (KVP and 3P Workshops), taking care of an adequate qualification concept in ergonomics and the intern and extern information exchange within the committees. This topic is established in the industrial engineering of the production area of the group. We are working interdisciplinary with the medical services, human resources, work council and the protection of labor. PMID- 22317399 TI - Ergonomics at Volkswagen Brasil. Multidisciplinary work to equalize health, productivity and quality. AB - Following the technological developments and presented to the multidisciplinary processes as automakers, Volkswagen Brazil, represented by its ergonomists, through this paper, shows the importance of ergonomic efficiency of management applied to various levels of life of a product, since its creation to its final implementation on production lines.The preventive work of ergonomists during the processes leading to production of a vehicle is accomplished through assessments on a simulated system called the Digital Factory. Since the initial stages to final product delivery there is a need for a multidisciplinary aligning the concepts of ergonomics, productivity and quality of product. Industrial Engineering, Process Engineering, ergonomists and workers are involved in the analysis made through the Workshop's showing the importance of discussion between the various users of the systems. The processes of series are also equipped with a set of certifications flow of job and planned audits on items that describe processes and applied ergonomics. PMID- 22317400 TI - ERGO-MTM model: an integrated approach to set working times based upon standardized working performance and controlled biomechanical load. AB - ERGO-MTM is an innovative model to set standard times of manual tasks. MTM, developed in the forties by industrial engineers, assigns a basic time to execute a given motion based on the concept of normal performance (speed, effort and precision). The traditional models to set a standard time then add to the basic time a fatigue allowance, applied on each individual motion, depending generally on the type of posture and on the load/force implied in the motion. To the light of the most recent ISO/CEN standards dealing with biomechanical load, the traditional models do not meet the requirements any more: it becomes mandatory to consider the load generated by the overall assignment of working tasks to a workstation to be compliant with the new ergonomics standards. ERGO-MTM is the solution: it determines a fatigue allowance (named Ergonomic Allowance), which is applied on the total workstation basic MTM time to allow the necessary recovery periods, enough to keep the biomechanical load within safety limits. The final result is a standard time based on a norm level of performance and a work sequence with a controlled biomechanical load. PMID- 22317401 TI - Interactive production planning and ergonomic assessment with Digital Human Models--introducing the Editor for Manual Work Activities (ema). AB - The aging workforce is a risk factor for manufacturing industries that contain many jobs with high physical workloads. Thus, ergonomic risk factors have to be avoided in early phases of production planning. This paper introduces a new tool for simulating manual work activities with 3D human models, the so-called emaPhi. For the most part, the emaPhi software is based on a unique modular approach including a number of complex operations that were theoretically developed and empirically validated by means of motion capturing technologies. Using these modules for defining the digital work process enables the production planner to compile human simulations more accurately and much quicker compared to any of the existing modeling tools. Features of the emaPhi software implementation, such as ergonomic evaluation and MTM-time analyses, and the workflow for practical application are presented. PMID- 22317402 TI - MultipLa--a tool for the combined overall estimation of various types of manual handling tasks. AB - In the 1990ies the German Federal Institute for Occupational Safety and Health (FIOSH) published "Key Indicator Methods" (KIM) for the evaluation of manual material handling tasks. These methods served as a national German implementation of the EU Manual Handling Directive (90/269/EEC). These methods allow the evaluation of individual handling tasks like lifting or pushing. KIM tools do not allow evaluating complex handling tasks like a combined lifting and pushing task. With respect to the needs at shop floor level (e.g. logistics), MultipLa tries to bridge that gap by means of an EXCEL based worksheet using the KIM philosophy. In the past several algorithms for a risk assessment had been developed. At the moment MultipLa is in a test phase at several automotive OEMs. PMID- 22317403 TI - Correlations in between EAWS and OCRA Index concerning the repetitive loads of the upper limbs in automobile manufacturing industries. AB - Upper limbs repetitive tasks are one of the main sources of risk for the workers of the manufacturing industries and the standards ISO 11228-3 and EN 1005-5 addressed this issue since 2007. EAWS (European Assembly Worksheet) is a 1st level ergonomic risk assessment method and it provides in its 4th section a score to measure the load level for the upper limbs based on a traffic light scheme. According to the relevant ISO/CEN standards, the OCRA Index is the preferred system to refer to in the evaluation of the biomechanical stress of hand-harm shoulder system. This correlation study is based on a 45 workstations sample coming from the automobile manufacturing industry. According to the results, EAWS4 shows an excellent correlation with OCRA index (Spearman's rho correlation index 0.95). Being EAWS based on biometric statistical data distribution, its typical application is the process design phase, but adopting a conservative approach in the interpretation of EAWS4 score for risk mapping purposes, it provides an equivalent "reaction" pattern (countermeasures to be taken in the production phase) with respect of OCRA Index with an Odds Ratio ranging from 0.89 (OR-matched) to 1.00 (OR-conservative). PMID- 22317404 TI - Ergonomics and workplace design: application of Ergo-UAS System in Fiat Group Automobiles. AB - Since 2008 Fiat Group Automobiles has introduced Ergo-UAS system for the balancing of production lines and to detect ergonomic issues. Ergo-UAS system integrates 2 specific methods: MTM-UAS for time measurement and EAWS as ergonomic method to evaluate biomechanical effort for each workstation. Fiat is using a software system to manage time evaluation and ergo characterization of production cycle (UAS) to perform line balancing and obtain allowance factor in all Italian car manufacturing plant. For new car models, starting from New Panda, FGA is applying Ergo-UAS for workplace design since the earliest phase of product development. This means that workplace design is based on information about new product, new layout, new work organization and is performed by a multidisciplinary team (Work Place Integration Team), focusing on several aspects of product and process: safety, quality and productivity. This allows to find and solve ergonomic threats before the start of production, by means of a strict cooperation between product development, engineering and design, manufacturing. Three examples of workstation design are presented in which application of Ergo UAS was determinant to find out initial excessive levels of biomechanical load and helped the process designer to improve the workstations and define limits of acceptability. Technical activities (on product or on process), or organizational changes, that have been implemented in order to solve the problems are presented. A comparison between "before" and "new" ergonomic scores necessary to bring workstations in acceptable conditions were made. PMID- 22317405 TI - Risk factors for incident carpal tunnel syndrome: results of a prospective cohort study of newly-hired workers. AB - Carpal tunnel syndrome is one of the most costly upper extremity disorders in the working population. Past literature has shown an association between personal and work factors to a case definition of carpal tunnel syndrome but little is known about the combined effects of these factors with the development of this disorder. Few studies have examined these associations in longitudinal studies. The purpose of this paper is to identify risk factors for incident carpal tunnel syndrome in a longitudinal study of workers across a wide range of occupations. PMID- 22317406 TI - Addressing the cultural complexity of OHS in the Australian mining industry. AB - This paper summarises the findings of the site assessments of ten pilot mine sites involved in a project entitled, Creating a world-leading OHS culture in the NSW Mining Industry which was undertaken for the New South Wales Mine Safety Advisory Council (NSW MSAC). NSW MSAC was established in 1998 in NSW Australia and aims to increase the emphasis on safety and health within the mining industry by reviewing and analyzing safety performance, setting strategic directions, providing advice and developing policy recommendations. The project itself aimed to deliver a self-sustaining method for achieving and monitoring continuous improvement in OHS culture and practice to the NSW mining industry. The pilot sites involved in the project tested a set of self-assessment tools to enable mines to assess and improve their own OHS culture and performance on key elements of an OHS management system. The tools allowed examination of the current OHS culture of the sites. Sites then used a participative planning process to develop an improvement plan. This paper provides summary data only, without identifying the individual sites that were the source of the data. PMID- 22317407 TI - Using MSD prevention for cultural change in mining: Queensland Government/Anglo Coal Industry partnership. AB - Queensland Mining has a strong focus on safety performance, but risk management of health, including Musculoskeletal Disorders (MSDs) continues to have a lower priority. The reliance on individual screening of workers and lower level approaches such as manual handling training is part of the coal mining 'culture'. Initiatives such as the New South Wales and Queensland Mining joint project to develop good practice guidance for mining has allowed for a more consistent message on participatory ergonomics and prevention of MSD. An evidence based practice approach, including the introduction of participatory ergonomics and safe design principles, was proposed to Anglo American Coal operations in Queensland. The project consisted of a skills analysis of current health personnel, design of a facilitated participatory ergonomics training program, site visits to identify good practice and champions, and a graduated mentoring program for health personnel. Early results demonstrate a number of sites are benefiting from site taskforces with a focus on positive performance outcomes. PMID- 22317408 TI - Application of ergonomics principles in underground mines through the Occupational Safety and Health Management System--OSHMS OHSAS 18.001:2007. AB - The underground mining activity is regarded as one of the activities that cause most accidents, deaths and illnesses in the world, highlighting the coal mines. This study examined how ergonomics principles can help improve this environment, reduce the number of accidents and occupational diseases, train and empower workers and leaders and humanize the activities of the duty cycle of an underground mine. For this, it was developed a conceptual model of safety managing and health at work for the underground mining through the incorporation of ergonomics principles in the Occupational Safety and Health Management System and OHSAS 18001 (2007). The elaboration of the model was based on analysis of the environments and stages of work in underground mines and the PDCA cycle to ensure continuous improvement. PMID- 22317409 TI - Challenges to care coordination posed by the use of multiple health IT applications. AB - Coordinating care for hospitalized patients requires the use of multiple sources of information. Using a macroergonomic framework (i.e. the work system model), we conducted interviews and observations of care managers involved in care coordination across transitions of care. When information is distributed across multiple health IT applications, care managers experience a range of challenges, including organizational barriers, technology design problems, skills and knowledge issues, and task performance demands (i.e. issues related to individual information processing and management and sharing of information). These challenges can be used as a checklist to evaluate the proposed IT infrastructure that will allow the integration of multiple health IT applications and, therefore, support coordination across transitions of care. PMID- 22317410 TI - Computer decision support tools in primary care. AB - Computer Decision Support Tools (CDSTs) can support clinicians at various stages of the care process and improve healthcare, but implementation of these tools has been difficult. In this study we examine the need for, the use of, and barriers and facilitators to the use of a CDST from a human factor perspective. Results show that there is a need for CDSTs, and that physicians do use well-developed CDSTs. However, there are also barriers against the use, such usability issues and problems fitting them into the clinical workflow. PMID- 22317411 TI - Considering social ergonomics: the effects of HIT on interpersonal relationships between patients and clinicians. AB - This study explored physicians' interactions with EHRs to understand the qualities that contribute to patient satisfaction with their use of the technologies and patient satisfaction with physician. Video-taped observations of 100 medical consultations were used to distinguish interaction patterns between physicians and EHRs. Quantified observational methods were used to contribute to ecological validity. Ten primary care physicians and 100 patients from five clinics participated in the study. Visits were videotaped and coded using an objective coding methodology to understand how physicians interacted with electronic health records. Results indicate, a variety of EHR interaction styles may be effective in providing patient-centered care. PMID- 22317412 TI - Can we make health IT safe enough for patients? AB - Health information technology (HIT) is widely believed to be an essential modality for improving the efficiency, effectiveness, and safety of healthcare, and has its adoption has been vigorously promoted. However, the safety of commercially available HIT systems has never been independently and rigorously assessed. This paper discusses critical issues to be considered in the development of safe and reliable HIT, and identifies a group of structural impediments that may slow or prevent the arrival of HIT that is actually safe enough for routine clinical use. It argues that this situation is analogous to NASA's promotion of the space shuttle not as an experimental, risky technology, but rather as a routine, ready-for-ordinary-use resource. PMID- 22317413 TI - Using HIT to deliver integrated care for the frail elderly in the UK: current barriers and future challenges. AB - In this paper we briefly describe the results of a 3 year project examining the use of Health Information Technologies (e.g., electronic patient record systems) to deliver integrated care. In particular, we focus on one group of patient (the frail elderly) and efforts to design an e-health supported healthcare pathway (the frail elderly pathway--FEP). The aim of FEP is to bring together clinicians and staff from health and social care and allow them to share patient information. Our findings show that progress in delivering a fully-supported and working FEP has been slow, not least because of the difficulties experienced by healthcare staff in using current IT systems. In addition, there are many strategic and technical issues which remain unresolved (e.g., systems interoperability). PMID- 22317414 TI - Spin your science into gold: direct to consumer marketing within social media platforms. AB - We describe the emerging issues related to warnings with respect to pharmaceutical company use of the internet as a vehicle for direct-to-consumer marketing (DTC) and market research. We describe the various techniques pharmaceutical companies have used to exploit this new communications medium which permits two way exchange of information. The Food and Drug Administration (FDA) has not issued any specific regulations to control internet based misbranding. We describe some examples of the FDA's application of historic regulations to pharmaceutical company use of this new medium and suggest. PMID- 22317415 TI - What do we mean by Human-Centered Design of Life-Critical Systems? AB - Human-centered design is not a new approach to design. Aerospace is a good example of a life-critical systems domain where participatory design was fully integrated, involving experimental test pilots and design engineers as well as many other actors of the aerospace engineering community. This paper provides six topics that are currently part of the requirements of the Ph.D. Program in Human Centered Design of the Florida Institute of Technology (FIT.) This Human-Centered Design program offers principles, methods and tools that support human-centered sustainable products such as mission or process control environments, cockpits and hospital operating rooms. It supports education and training of design thinkers who are natural leaders, and understand complex relationships among technology, organizations and people. We all need to understand what we want to do with technology, how we should organize ourselves to a better life and finally find out whom we are and have become. Human-centered design is being developed for all these reasons and issues. PMID- 22317416 TI - Complexity analysis of the Next Gen Air Traffic Management System: trajectory based operations. AB - According to Federal Aviation Administration traffic predictions currently our Air Traffic Management (ATM) system is operating at 150 percent capacity; forecasting that within the next two decades, the traffic with increase to a staggering 250 percent [17]. This will require a major redesign of our system. Today's ATM system is complex. It is designed to safely, economically, and efficiently provide air traffic services through the cost-effective provision of facilities and seamless services in collaboration with multiple agents however, contrary the vision, the system is loosely integrated and is suffering tremendously from antiquated equipment and saturated airways. The new Next Generation (Next Gen) ATM system is designed to transform the current system into an agile, robust and responsive set of operations that are designed to safely manage the growing needs of the projected increasingly complex, diverse set of air transportation system users and massive projected worldwide traffic rates. This new revolutionary technology-centric system is dynamically complex and is much more sophisticated than it's soon to be predecessor. ATM system failures could yield large scale catastrophic consequences as it is a safety critical system. This work will attempt to describe complexity and the complex nature of the NextGen ATM system and Trajectory Based Operational. Complex human factors interactions within Next Gen will be analyzed using a proposed dual experimental approach designed to identify hazards, gaps and elicit emergent hazards that would not be visible if conducted in isolation. Suggestions will be made along with a proposal for future human factors research in the TBO safety critical Next Gen environment. PMID- 22317417 TI - Improving flight condition situational awareness through Human Centered Design. AB - In aviation, there is currently a lack of accurate and timely situational information, specifically weather data, which is essential when dealing with the unpredictable complexities that can arise while flying. For example, weather conditions that require immediate evasive action by the flight crew, such as isolated heavy rain, micro bursts, and atmospheric turbulence, require that the flight crew receive near real-time and precise information about the type, position, and intensity of those conditions. Human factors issues arise in considering how to display the various sources of weather information to the users of that information and how to integrate this display into the existing environment. In designing weather information display systems, it is necessary to meet the demands of different users, which requires an examination of the way in which the users process and use weather information. Using Human Centered Design methodologies and concepts will result in a safer, more efficient and more intuitive solution. Specific goals of this approach include 1) Enabling better fuel planning; 2) Allowing better divert strategies; 3) Ensuring pilots, navigators, dispatchers and mission planners are referencing weather from the same sources; 4) Improving aircrew awareness of aviation hazards such as turbulence, icing, hail and convective activity; 5) Addressing inconsistent availability of hazard forecasts outside the United States Air Defense Identification Zone (ADIZ); and 6) Promoting goal driven approaches versus event driven (prediction). PMID- 22317418 TI - The development of a virtual camera system for astronaut-rover planetary exploration. AB - A virtual assistant is being developed for use by astronauts as they use rovers to explore the surface of other planets. This interactive database, called the Virtual Camera (VC), is an interactive database that allows the user to have better situational awareness for exploration. It can be used for training, data analysis and augmentation of actual surface exploration. This paper describes the development efforts and Human-Computer Interaction considerations for implementing a first-generation VC on a tablet mobile computer device. Scenarios for use will be presented. Evaluation and success criteria such as efficiency in terms of processing time and precision situational awareness, learnability, usability, and robustness will also be presented. Initial testing and the impact of HCI design considerations of manipulation and improvement in situational awareness using a prototype VC will be discussed. PMID- 22317419 TI - Advanced interaction media in nuclear power plant control rooms. AB - The shift from analog to digital Instruments (related mainly to information visualization) and Controls in Nuclear Power Plant Main Control Rooms (NPP MCR) is a central current topic of investigation. In NPP MCR, digitalization was implemented gradually, analog and digital systems still coexisting for the two main systems related to safety--Safety Instruments and Control System (SICS) and Process Instruments and Controls System (PICS). My ongoing research focuses on the introduction of Advanced Interaction Media (AIM) such as stereoscopic 3D visualization and multi-touch surfaces in control rooms. This paper proposes a Safety-Centric approach for gathering the Design Rationale needed in the specification of such novel AIM concepts as well as their evaluation through user tests. Beyond methodological research, the final output of the current research is to build an experimental simulator aiming to enhance improvements in Human Systems Integration (HSI). This paper provides an overview of the topics under consideration. PMID- 22317420 TI - Automations influence on nuclear power plants: a look at three accidents and how automation played a role. AB - Nuclear power is one of the ways that we can design an efficient sustainable future. Automation is the primary system used to assist operators in the task of monitoring and controlling nuclear power plants (NPP). Automation performs tasks such as assessing the status of the plant's operations as well as making real time life critical situational specific decisions. While the advantages and disadvantages of automation are well studied in variety of domains, accidents remind us that there is still vulnerability to unknown variables. This paper will look at the effects of automation within three NPP accidents and incidents and will consider why automation failed in preventing these accidents from occurring. It will also review the accidents at the Three Mile Island, Chernobyl, and Fukushima Daiichi NPP's in order to determine where better use of automation could have resulted in a more desirable outcome. PMID- 22317421 TI - Human-machine cooperation: a solution for life-critical systems? AB - Decision-making plays an important role in life-critical systems. It entails cognitive functions such as monitoring, as well as fault prevention and recovery. Three kinds of objectives are typically considered: safety, efficiency and comfort. People involved in the control and management of such systems provide two kinds of contributions: positive with their unique involvement and capacity to deal with the unexpected; and negative with their ability to make errors. In the negative view, people are the problem and need to be supervised by regulatory systems in the form of operational constraints or by design. In the positive view, people are the solution and lead the game; they are decision-makers. The former view also deals with error resistance, and the latter with error tolerance, which, for example, enables cooperation between people and decision support systems (DSS). In the real life, both views should be considered with respect to appropriate situational factors, such as time constraints and very dangerous environments. This is known as function allocation between people and systems. This paper presents a possibility to reconcile both approaches into a joint human-machine organization, where the main dimensioning factors are safety and complexity. A framework for cooperative and fault tolerant systems is proposed, and illustrated by an example in Air Traffic Control. PMID- 22317422 TI - Rethinking healthcare as a safety--critical industry. AB - The discipline of ergonomics, or human factors engineering, has made substantial contributions to both the development of a science of safety, and to the improvement of safety in a wide variety of hazardous industries, including nuclear power, aviation, shipping, energy extraction and refining, military operations, and finance. It is notable that healthcare, which in most advanced societies is a substantial sector of the economy (eg, 15% of US gross domestic product) and has been associated with large volumes of potentially preventable morbidity and mortality, has heretofore not been viewed as a safety-critical industry. This paper proposes that improving safety performance in healthcare must involve a re-envisioning of healthcare itself as a safety-critical industry, but one with considerable differences from most engineered safety-critical systems. This has implications both for healthcare, and for conceptions of safety critical industries. PMID- 22317423 TI - Evaluating work and training within an intercommunicating process of change: reflections drawn from a case study on a chemicals industrial company in Portugal. AB - The new challenges in the field of Health and Safety at Work require the implementation of more comprehensive and participatory interventions, in order to have a real impact on the working conditions. Matriosca Model has sought over the years to involve workers in the construction of new working conditions, promoting transformation through training and recreating training from the transformation. This article seeks to present some of the results of the implementation of the Matriosca Model on a chemicals industrial company regarding the many changes that it promoted, how these changes have evolved through time, how the dimensions of training and transformation interact and what the participants' perception of the intervention was. The conclusions drawn allow a richer evaluation of the process, which can enhance the intercommunicating nature between training and transformation, and what impact this has on the actual work. PMID- 22317424 TI - Ergonomic analysis of work activity for the purpose of developing training programs: the contribution of ergonomics to vocational didactics. AB - Questions related to job skills and the teaching situations that best promote skill development are investigated by specialists in various fields, notably among them, ergonomists. This paper presents the findings of an ergonomic intervention study whose aim was to develop a meat-deboning training program by taking into account both the training content to be constructed and the working conditions that might facilitate or hinder skill development. One-on-one interviews and group discussions, on-the-job and videotape playback observations, as well as self-confrontation interviews were carried out. Activity analysis revealed major variability in work methods. The reasoning behind the experienced workers' actions and the experiential job knowledge they had developed were brought to light and served to develop the training content. The determining factors in the choice of work methods were identified, allowing adjustments to be made to the working conditions that might hinder skill development. The ergonomic process that implied taking working conditions into account in our study may make a significant contribution to vocational didactics, which is based on the cognitive analysis of work for the purpose of improving the effectiveness of job skills training. PMID- 22317425 TI - Instruments of trainers' activity: the use of refentials in processes of recognition and validation of prior learning. AB - In Portugal, recognition and validation of prior learning has emerged as an important training practice. Since 2001, it has been possible to obtain an academic certification by valuing learning, regardless of its origin. The current study was conducted with trainers and adults who were involved in processes of recognition, validation and certification of competences (RVCC). This research study, using qualitative research methods, described and tried to develop the comprehension of the use of referentials as instruments of trainers' activity. This analysis focused especially on three aspects: (i) the organization and development of RVCC processes; (ii) trainers' role in these processes; and (iii) the use of a referential as an instrument of activity. The findings suggested that the referential used in these processes mediates trainers' activity, functioning as competences identification guides. After an initial appropriation, trainers reconceptualize the referential by creating their own grids. There is clear variability in the use of this guiding document. Trainers revealed ambivalence towards the autonomy that they have in their work activity. Although they assess the opportunity to individually and freely create their work instruments in a positive way, they also lack a collective support and validation. PMID- 22317426 TI - Proposal for training of workers and researchers as from the participatory return of research results in workers' health. AB - This study streams from a perspective of Workers' Health as a field of intervention where worker's experience on the process of illness is essential to understand and generate changes in the work process, and to contribute to develop knowledge in this area. We intended to collaborate in the training of researchers and nursing workers as a means of contributing to amplify their knowledge related to work and health conditions. As a motto to promote dialogue between researchers and workers, we organized workshops to discuss the results of an epidemiological study on the work-health relationships in nursing. Ten workshops were conducted at two federal public hospitals, in the city of Rio de Janeiro, Brazil. The main aspects discussed during the workshops revealed (i) work nuances for which the questionnaire was not sufficiently sensitive, (ii) some associations between different aspects of the survey, dealt with in the questionnaires, and (iii) recognition that some aspects shown in the epidemiological results were experienced at work. One can appreciate that the proposal presented here contributed to the training of researchers and workers, amplifying their knowledge and contributing to the development of the activity. PMID- 22317427 TI - "Meetings on the work": an analysis device for understanding the articulation between outsourcing and other organizational innovations. AB - The purpose of this article is to discuss professional education and training programs offered to teams of operators by the main company in the area of Bacia de Campos (Petrobras), Rio de Janeiro, Brazil. It also discusses the necessary skills to the new functions derived from the implementation of an organizational innovation, the polyvalence, and how such innovation has impacted operators' activity. By using elements of WEA and the device "Meetings on the Work" it was possible to gain a better understanding of both the distance between the dimensions of prescribed work and real work, and the articulation between outsourcing and the proposition of polyvalence, which have stimulated the creation of new functions, namely, the polyvalent operator and the operator maintainer, this latter being in fact an evolvement of the first. PMID- 22317428 TI - Using experimental design to define boundary manikins. AB - When evaluating human-machine interaction it is central to consider anthropometric diversity to ensure intended accommodation levels. A well-known method is the use of boundary cases where manikins with extreme but likely measurement combinations are derived by mathematical treatment of anthropometric data. The supposition by that method is that the use of these manikins will facilitate accommodation of the expected part of the total, less extreme, population. In literature sources there are differences in how many and in what way these manikins should be defined. A similar field to the boundary case method is the use of experimental design in where relationships between affecting factors of a process is studied by a systematic approach. This paper examines the possibilities to adopt methodology used in experimental design to define a group of manikins. Different experimental designs were adopted to be used together with a confidence region and its axes. The result from the study shows that it is possible to adapt the methodology of experimental design when creating groups of manikins. The size of these groups of manikins depends heavily on the number of key measurements but also on the type of chosen experimental design. PMID- 22317429 TI - Anthropometric change: implications for office ergonomics. AB - Well-designed office workspaces require good anthropometric data in order to accommodate variability in the worker population. The recent obesity epidemic carries with it a number of anthropometric changes that have significant impact on design. We examine anthropometric change among US civilians over the last 50 years, and then examine that change in a subset of the US population--the US military--as military data sets often have more ergonomic dimensions than civilian ones. The civilian mean stature increased throughout the period 1962 to 2006 for both males and females. However, the rate of increase in mean weight was considerably faster. As a result, the male obesity rate changed from 10.7% in 1962 to 31.3% in 2006. The female change for the same period was 15.8% to 33.2%. In the Army, the proportion of obesity increased from 3.6% to 20.9%, in males. In the absence of national US ergonomic data, we demonstrate one approach to tracking civilian change in these dimensions, applying military height/weight regression equations to the civilian population estimates. This approach is useful for population monitoring but is not suitable for establishing new design limits, as regression estimates likely underestimate the change at the ends of the distribution. PMID- 22317430 TI - Influence of anthropometry on meat-packing plant workers: an approach to the shoulder joint. AB - This study was conducted with 90 poultry slaughterhouse workers, which perform the function of removing chicken parts from the conveyor belt, and sample was composed of 66 women (33.5 +/- 6.5 years) and 24 men (35.7 +/- 7.2 years), aiming to analyze the influence of anthropometry in the shoulder joint of these workers. Body discomfort was evaluated by a human body diagram, being applied at the end of the work shift. The anthropometric measurement of shoulder was performed by measuring the height of the acromion process, being compared with the height of the conveyor belt. Analysis of the results was performed by descriptive statistics, mean, standard deviation, percentage and percentiles 5%, 50% and 95%. It was found that the height of the conveyor belt was 1.74 meters, while the average shoulder height of workers was 1.38 meters for percentile 5%, 1.41 meters for percentile 50% and 1.65 meters for percentile 95%. The discomfort regions were shoulder 45%, neck 29%, column 26%, arms 23%, and wrists and hand 20%. The upper limb assessment was performed with percentile 5% through the Rapid Upper Limb Assessment method, resulting in a final score > 7, indicating the need for adjustments of the work organization. It was concluded that the workplace does not meet the workers' anthropometric characteristics, mainly affecting the shoulder joint, and correction ergonomics becomes necessary so that the workers involved in this study can perform their functions with health, comfort and safety. PMID- 22317431 TI - 1D and 3D anthropometric data application on public transport vehicle layout and on oil and gas laboratories work environment design. AB - The goal of this paper is to present 1D and 3D anthropometric data applied to two distinct design situations: one related to the interior layout of a public transport vehicle and another one related to oil and gas laboratories work environment design. On this study, the 1D anthropometric data were extracted from the Brazilian anthropometric database developed by INT and the 3D anthropometric data were obtained using a Cyberware 3D whole body scanner. A second purpose of this paper is to present the 3D human scanning data as a tool that can help designers on decision making. PMID- 22317432 TI - Determining anthropometric variables as a tool in the preparation of furniture and designs of interior spaces: the case of children 6 to 11 years old of Vicosa, State of Minas Gerais, Brazil. AB - The adequacy of facilities and the individual securities in their different age groups is importance to ensure greater functionality to them, allowing full development of daily activities. For this to occur more efficiently it is necessary the use of ergonomics which can ensure more comfort and safety for end users of products and spaces. The present study aimed to measure body dimensions of a representative sample of children aged 6 to 11 years old, children of graduate and pos graduate students, faculty and staff of the Federal University of Vicosa and also residents of the city of Vicosa, State of Minas Gerais, Brazil, coming from different municipalities of State of Minas Gerais, to organize a database that will provide the furniture industry, anthropometric variables more appropriate to design products for both the leisure activities, and for the school sector. To realize this research we used the methodology proposed by the authors Panero and Zelnik, based on samples distributed in six age groups, and providing a measurement of 10 variables. By applying the methodology to the field was possible to compare the observed data, with the tables of the aforementioned authors. The main results revealed a significant variation of the 10 variables analyzed, and it is believed that this variation could lead to possible flaws in the designs of products that use the data from these authors. The completion of the study provided data on Vicosa considered more appropriate for the design of products and environments for the population of the study, considering age and region, of Brazil (State of Minas Gerais) and it is believed that the future may expand to the Brazilian population, with the progress of study of this nature. PMID- 22317433 TI - Accessibility and ergonomic analysis for banking cash. AB - Ergonomics and accessibility in banking has been the subject of numerous discussions, and in this work proposed by the partnership of companies and NR TN Mobile Work Safety and Occupational Medicine, aimed to analyze the service box and propose the development of a project to the teller accessible account of both the legal aspects regarding the factors inherent in banking, focusing primarily on the interface of the worker and the client user. PMID- 22317434 TI - Police training course for agents--entry into the profession and also into the distinction between men and women. AB - An exploratory study was conducted about the initial training of the Public Security Police with the aim to understand the role of this initial training in the distinction between the work of men and women in the police force. This study is part of a broader study about the entry of women into typically male professions. After documental analysis and interviews to students, trainers and school board members, it was concluded that women face greater difficulties in the access to the profession. Moreover, female qualities like the capacity to dialogue are devalued. Nevertheless, women represent an important work tool for the police force. The stigma of physical strength was also encountered and identified in the previous study conducted with elements of the police force. This fact leads us to believe that these stereotypes usually associated with women are defended by elements of the institution. PMID- 22317435 TI - Safe and healthy integration into semiskilled jobs: does gender matter? AB - Women report fewer injuries than men when they are young, but report a higher proportion of professional diseases later in life (35 years +). Understanding early work conditions that lead to postponed health outcomes is necessary if we are to prevent women's injury as well as men's. Introduction to work and safe integration programs are often put forward to prevent injuries among youth. This paper aims to illustrate some differences in the job introduction / integration process for men and women and to discuss some gender-based Occupational Health and Safety (OHS) implications. Data come from two waves of interviews with 31 students enrolled in vocational training for a semiskilled trade. Results demonstrated differences between men and women: trades chosen, OHS complaints, supervising patterns, integration to work, etc. Women often choose customer service jobs, have less formal supervision and are often left to themselves when learning to do their job. Men declared more accidents while women reported more musculoskeletal symptoms. Findings from this research suggest young women's OHS issues should not be trivialized and that specific youth prevention programs for sectors where women are more present, such as customer service, should be developed. PMID- 22317436 TI - The entry of women in predominantly male professions: when training supports the search of alternative ways of organizing work time. AB - Following a research carried out on the integration of women in professional areas predominantly for men, this paper intends to present and debate the project of a training course which aims the transformation of the organization of work schedules in order to improve the well-being of the workers involved. The conception of training courses with this type of objective involves the confrontation and debate between the "invested skills" of the trainers and the "constituted skills" of the trainees. But will this paradigm remain intact when applied to training courses permeated by the gender dimension? That is what one will try to realize with the effective implementation of a training course, whose reflection will allow, ultimately, to enrich our understanding on gender, work, health and training. PMID- 22317437 TI - Health and safety of students in vocational training in Quebec: a gender issue? AB - Health and safety issues in a vocational training center were explored in this study. Several sources and methods were used: group interviews with students in traditionally female [F] and male [M] trades, i.e. hairdressing (7 F) and automated systems electromechanics (8 M, 1 F); self-administered questionnaires on injuries sustained at the school; observations of activities in these programs; and analysis of ministerial documents. Findings indicate that the partially divergent ways that OHS is addressed in these programs cannot be explained only by the specific characteristics of the two trades. Some aspects put female students in hairdressing at a disadvantage: status accorded to OHS in the study programs, learning activities, and conditions for learning and managing prevention and injuries. The discussion focuses on a gender-differentiated analysis, the importance of improving the way OHS is addressed in the programs, in particular, those primarily involving female students, and the need to pursue research. In addition, the results from individual interviews with women (5 F) training for non-traditional trades lead to discussion on the interrelated effects of sex-based gender and professional gender. PMID- 22317438 TI - The use of a website as an interaction and training device in health, gender and work in schools. AB - The objective of this paper is to introduce the Website "Encontros sobre a vida, a saude e o trabalho nas escolas publicas" (Encounters of life, health and work in public schools). It was designed viewing to contribute to the generation of changes regarding the meanings attributed to work done by all professionals acting in Brazilian public schools, in their relationship to health. We have tried to create a space conducive to reflection and invention of different ways of action towards the struggle for health of the protagonists of the school units. We present the Website's different ambients, such as the one for availability of Training materials, Discussion Forums and the Observatory of facts and events related to the topic. We point out the analysis of a dialogue between the Formaction Program in Health, Gender and Work at Schools. Through the displaying of dialogs that mobilized the training participants we observed a process of collective analysis of the situations that occur at meetings, allowing other interpretation possibilities by the different parties. In the case focused, a nursery assistant (male), in the dialogue, is forced to review his description of the activity, initially, portrayed as simple. PMID- 22317439 TI - Disparities between industrial and surgical ergonomics. AB - A surgeon's work environment and working conditions are often harsher than those of an industrial worker. Accepted principles and regulations of ergonomics in manufacturing are largely ignored or absent in the medical/surgical domain. Examples include poor surgical tool handle design, awkward and stressful surgical postures, and prolonged standing without breaks and without a foot mat. In these and other areas, there are documented "best practices" for industrial hygiene and ergonomics that are not yet widely accepted for surgery. There is support in the literature for innovations in surgical ergonomics, yet adoption is not widespread. In the absence of these ergonomic principles, surgical repetitive strain injuries in minimally invasive surgery are reaching epidemic levels. As ergonomists, it falls upon us to understand why current solutions have not been widely adopted within this domain, and to derive solutions to the unique challenges of surgery. PMID- 22317440 TI - Standardization of surgical procedures for identifying best practices and training. AB - A taxonomy was developed a) to describe surgical procedures with sufficient detail to review differences among surgeons, b) to examine the relationship between individual technique and outcomes, c) to enable surgeons to standardize technique around best practices and d) to identify clinical-evidence-based key points of teaching and assessment for surgical training. Sixty-seven microvascular anastomoses were recorded through video cameras mounted in the dissecting microscope. A hierarchical task analysis was used to decompose the observed procedures into successive levels of detail. The results were then presented to individual and small groups of microvascular surgeons to help define steps and step attributes necessary to describe a procedure so that other surgeons can perform the procedure exactly the same way. Coincidently, it was found that because the surgeons' attention is confined to a very small field of view in which they can see only the veins and arteries and the ends of their instruments, they often have difficulty communicating with others in the operating room. Analyses of selected cases using the proposed taxonomy shows how subtle details are revealed that may affect outcomes, and indicate specific training needs. By comparing different methods and outcomes, it should be possible to identify best practices for given conditions. PMID- 22317441 TI - Distal upper extremity musculoskeletal risk factors associated with colonoscopy. AB - Gastroenterologists are at increased risk for developing recurrent thumb, hand, and elbow pain due to colonoscopy procedures. We evaluated forearm muscle loads and wrist postures during routine colonoscopy (N=12 gastroenterologists) to understand distal upper extremity musculoskeletal risk factors associated with the 4 different subtasks of colonoscopy. Bilateral forearm extensor carpiradialis (ECR) and flexor digitorum superficialis (FDS) surface electromyography and bilateral wrist postures were recorded continuously. The mean duration of colonoscopy was 24.2 (+/- 12.1) minutes and was dominated by the withdrawal subtask [13.7 (+/- 8.8) min] followed by right colon insertion [5.8 (+/- 4.8) min], left colon insertion [3.5 (+/- 3.1) min], and retroflexion [1.2 (+/- 2.1) min]. Median (APDF50) and peak (APDF90) left forearm muscle activity was significantly greater than right forearm muscle activity across all subtasks. Median and peak ECR muscle activity was significantly greater during the left and right colon insertion subtasks compared to retroflexion. Both wrists were predominantly in wrist extension during all phases of colonoscopy. The left forearm muscle activity was higher than right forearm activity due to differences in wrist posture and grip force. The risk factors for the left hand may be reduced with alternative designs and support mechanisms for the colonoscope head. PMID- 22317442 TI - Ergonomic considerations in natural orifice translumenal endoscopic surgery (NOTES): a case study. AB - Surgical technique evolved from traditional open surgery to laparoscopic surgery, offering patients reduced pain and quick recovery. Recently, a new approach called natural orifice translumenal endoscopic surgery (NOTES) has emerged. In NOTES, procedures may be transvaginal, transgastric, or transrectal or transesophageal. NOTES procedures present new ergonomic challenges to surgeons due to visualization and tissue manipulation challenges. An ergonomic analysis of NOTES cholecystectomy was conducted. As there is currently no standardization for performing NOTES, this analysis presents the results as a case study. Results showed NOTES procedures impose unique limitations on the surgeon's ability to perform surgical tasks autonomously, requiring collaboration and coordination amongst the surgical team members. PMID- 22317443 TI - Ergonomic risk assessment of nasogastric tube placement and implications for design and training. AB - The placement of nasogastric (NG) tubes is known to be prone to error and may lead to serious issues for patient safety and wellbeing. In some instances these have been catastrophic and resulted in the death of the patient. This study sought to explore the potential risks associated with this procedure through the use of systematic prospective risk assessment. The research team used the Prospective Hazard Analysis (PHA) toolkit developed by Ward et al (2010) . The study has shown a wide number of risks that cover equipment design, work organisation, and training issues. The link between equipment design and training provides an important example of the need for a systematic approach to reducing errors and improving resilience in this aspect of healthcare. PMID- 22317444 TI - Ergonomics of novices and experts during simulated endotracheal intubation. AB - Endotracheal Intubation (ETI) is an airway procedure commonly used to secure the airway for a variety of medical conditions. Proficiency in ETI procedures requires significant clinical experience and insufficient data currently exists describing the physical ergonomics of successful direct laryngoscopy. The research objectives of this study were to examine how ETI time, error and practitioner biomechanics varied among clinical experience levels and hospital bed heights. The participant population included novice and expert personnel, differentiated by their exposure to ETI procedures. Participants used a standard laryngoscope and blade to perform ETI trials on an airway manikin trainer at predesigned hospital bed heights. Participants were evaluated based on ETI time and accuracy, as well as wrist postures and muscle utilization. Hospital bed height did not affect task completion time, error rates or muscle utilization. Expert participants exhibited less ulnar deviation and forearm supination during task trials, as well as a higher utilization of the bicep brachii and anterior deltoid muscles. Expert grasped instrumentation differently, requiring less wrist manipulation required to achieve ideal instrument positions. By encouraging ergonomic best-practices in hand and arm postures during ETI training, the opportunity exists to improve patient safety and reduce the learning curve associated with ETI procedures. PMID- 22317445 TI - Review of practices for keeping people with disabilities in employment: moving beyond the concept of compensation to implement a developmental approach. AB - In France, there are strict laws in place to ensure that people with disabilities have access to, and can remain in employment. In this context, many businesses have "group agreements", to support and fund in-house actions in this area. For the last five years, as part of our work as consultant ergonomists, we have carried out over fifty ergonomics interventions for one of our clients to adapt the working environment for persons with disabilities. This paper presents an analysis of our practices to adapt working environment for employees with disabilities by means of a review of these different interventions. This analysis of practices specifically focuses on an issue we consider to be of vital importance: how to get past the concept of an impairment which can be compensated for with technical solutions, a concept in which both French legislation, and the practices of certain professionals working in the field of occupational disability are firmly rooted, and move towards a developmental approach, with the aim of designing an "enabling environment" [2-4,13]. PMID- 22317446 TI - Ergonomics and the inclusion of people with disabilities in a Brazilian workplace. AB - The customization of a secretary workstation at a drama school was the objective of this case study. The investigation involved a 25-year-old illiterate woman with intellectual disabilities and low vision that had been been attending, for over 12 years, a state school for people with disabilities. The customization process, operationalized after a diagnosis was made, focused on environmental rearrangements, with the purpose of meeting the physical and social demands of the workstation. The results of this research are configured in an ergonomic analysis of work associated with an inventory of social skills, applied to people living directly with the participant. Preliminary evaluations indicated the degree of adjustment of labor demands to the personal characteristics of the participant in the customized job. PMID- 22317447 TI - Including the people with disabilities at work: a case study of the job of bricklayer in civil construction in Brazil. AB - The aim of this paper is to present the results of the evaluation of the job of bricklayer in the construction industry to determine the profile of workers with disabilities who could perform this function and what adjustments are needed. The methods and techniques used in the field study were: direct observation of the activities and the environment, interviews with bricklayers on building sites, a video and photographic record of tasks being carried out to analyze the job of bricklayer, software resources were used. This study set out the disabilities most commonly caused by work accidents in the civil construction industry and simulated the conditions of the individuals to determine whether they could perform the activities of this function and what adaptations are needed. It was observed that workers with hearing impairments could perform activities without any change in the workplace and individuals who had had a leg or foot amputated need to use appropriate prostheses to perform the activities of the function. Thus, it was shown that the activity of professionals with experience in Ergonomics is essential since, by the activity of gathering data and analysing the physical, cognitive and organizational requirements of jobs and by collecting data on and analysing the functional capabilities of the worker with a disability, adaptations to jobs can be adequately defined. PMID- 22317448 TI - Issues concerning scientific production of including people with disabilities at work. AB - This article presents the results of a survey carried out on leading periodicals in the areas of Ergonomics, Physiotherapy and Occupational Therapy, the aim of which was to identify scientific publications on the inclusion at work of people with disabilities. The survey of articles published on this topic in the following journals was conducted in December 2010: Applied Ergonomics, Ergonomics, the International Journal of Industrial Ergonomics, Disability and Rehabilitation, and the Journal of Occupational Rehabilitation. The survey covered issues published between 2000 and 2010 and was conducted electronically using the CAPES Periodicals Portal. To collect the articles, it was necessary to check the articles published in each of the issues of each volume of these periodicals. This is how the articles on the topic in question were found. There were 27 articles on the topic of inclusion at work of people with disabilities, of which 13 were published in the Journal of Occupational Rehabilitation and 12 in Disability and Rehabilitation. Thus, it is clear that the issue in question is still a subject that is seldom dealt with in these publications and it is noted that only two articles were published in Ergonomics journals in this period, thus confirming the paucity of scientific publications on this subject. PMID- 22317449 TI - Ergonomic aspects of design of a cap with electronic obstacle detector for use by visually impaired people. AB - The first sentence of the Abstract should follow the word "Abstract." on the same line. The abstract should be clear, descriptive, self-explanatory and no longer than 200 words. It should also be suitable for publication in abstracting services. Do not include references or formulae in the abstract. PMID- 22317450 TI - Ergonomics, design universal and fashion. AB - People who lie beyond the "standard" model of users often come up against barriers when using fashion products, especially clothing, the design of which ought to give special attention to comfort, security and well-being. The principles of universal design seek to extend the design process for products manufactured in bulk so as to include people who, because of their personal characteristics or physical conditions, are at an extreme end of some dimension of performance, whether this is to do with sight, hearing, reach or manipulation. Ergonomics, a discipline anchored on scientific data, regards human beings as the central focus of its operations and, consequently, offers various forms of support to applying universal design in product development. In this context, this paper sets out a reflection on applying the seven principles of universal design to fashion products and clothing with a view to targeting such principles as recommendations that will guide the early stages of developing these products, and establish strategies for market expansion, thereby increasing the volume of production and reducing prices. PMID- 22317451 TI - Design of therapeutic clothing for sensory stimulation of children with psychomotor delay. AB - This research work was based on an experimental concept of functional clothing for children with psychomotor development limitations. No matter the analyzed pathology, all these children need sensorial stimulation because of their psychomotor difficulties, especially at fine motor skills level. The main objective was to develop functional and comfortable clothing with sensorial stimulation elements (colours, textures, fragrances, sounds, etc.). It is intended, on the one hand, to increase the autonomy of the children in what concerns the act of dressing/undressing and, on the other hand, to stimulate their learning, coordination and self-esteem. A study about the specific needs of these children concerning clothing was worked out, which consisted in inquiring their parents and therapists. Based on the inquiries results, bibliographic revision in the area of therapeutic/ interactive clothing and analysis of didactic and therapeutic material catalogues we developed a clothing prototype (sweat-shirt). The prototype was then tested by the children of the study sample and the test results were, once again, explained by the parents through the fulfilling of a prototype evaluation inquiry. This study supplied some important conclusions, more directed to the confirmation of the theme significance and to the definition of a methodology to be used in future research. PMID- 22317452 TI - Colour and inclusivity: a visual communication design project with older people. AB - In an ideal world, inclusive products and services would be the standard and not the exception. This paper presents a systematic approach to an overlap between Visual Communication Design, Printed Colour and Inclusive Design, for older people, with the aim to develop of a set of research-based ageing and ergonomics centred communication design guidelines and recommendations for printed material (analogical displays). The approach included an initial extensive literature review in the area of colour, older people and ergonomics issues and vision common diseases, communication design. The second phase was the implementation of an experiment to measure the different colour experiences of the participants in two sample groups (one in UK and another one in Portugal), using printed material, to find out the colours one should use in analogical communication material, being aware of the colour contrast importance (foreground versus background) and the difficulties experienced by older people to read and understand lettering, signs. As main contribution of this research project, we developed a set of guidelines and recommendations based on the reviewed literature and the sample groups' findings, trying to demonstrate the importance of these guidelines when conceiving a new communicational design project in a way this project will achieve vision comfort and understandability, especially for older people, in an inclusive design perspective. PMID- 22317453 TI - Chemical toilet for persons with disabilities: proposal for an urban furniture affordable. AB - Street furniture is an important element to the social and democratic life in the cities. In this case, public restrooms must be available to practically all kinds of citizens that inhabit the city. However disabled people have many difficulties in using the existing models, particularly public chemical toilets. Through a design project, a new proposition for a public chemical toilet addressed to wheelchair users was conceived. In this way, the main aspect of this work refers to the actual participation of the disabled expressing their opinion through interviews and usability analysis as well as the observation on technical recommendations for accessibility. PMID- 22317454 TI - Inclusive design--assistive technology for people with cerebral palsy. AB - The first sentence of the Abstract should follow the word "Abstract." on the same line. The abstract should be clear, descriptive, self-explanatory and no longer than 200 words. It should also be suitable for publication in abstracting services. Do not include references or formulae in the abstract. This study reports the work of the Inclusive Design research project conducted with a group of children with cerebral palsy Our project has been working with Assistive Technology and has been developing an expanded mouse and a keyboard. Nowadays, we are working as a researcher of Cognitive Ergonomics and of Inclusive Education. The goal of our project is to establish an interdisciplinary study that focus the developing of a research in Ergonomics Design, contributing to improve the assistance to people with special needs. METHOD: One applied the pedagogical approach, using Vygotsky's Social-historic Theory that advocates the concept of each individual's experiences are important to improve them. The development methodology was based on user-centered design. RESULTS: The results showed that as long as the students applied the new technologies they developed superior psychological processes towards social interaction, autonomy, taking part in class activities more efficiently. Also, we verified how important the new technologies in class were, considering the methodologies, objectives full and effective described on this study. This way, we do hope, from the data obtained on this research, to contribute with the ones who believe that the improvement of handicap students' inclusion in class is a reality. PMID- 22317455 TI - Inclusion of people with disabilities in the production system of a footwear industry. AB - This article presents a study on the inclusion of people with disabilities (mainly mental impairment) in the workforce of a shoe company. The items that could impact on the success of inclusion were identified, and this included employees and other individuals taking part in the process. The inclusion process identified the interests, likes and dislikes of each employee with disabilities and correlated these with the activities available in the company. The case study evaluated the quality of the inclusion through interviews, questionnaires and an assessment of production efficiency. The results showed that inclusion did not adversely affect production, and highlighted that staff with disabilities do their work correctly. According to all employees interviewed, the inclusion of staff with disabilities improved the relationship of the boss with all of the staff and also led to the work environment being enhanced. The final evaluation is that the company's policy of inclusion succeeded. PMID- 22317456 TI - Research the mobile phone operation interfaces for vision-impairment. AB - Due to the vision-impaired users commonly having difficulty with mobile-phone function operations and adaption any manufacturer's user interface design, the goals for this research are established for evaluating how to improve for them the function operation convenience and user interfaces of either mobile phones or electronic appliances in the market currently. After applying collecting back 30 effective questionnaires from 30 vision-impairment, the comments have been concluded from this research include: (1) All mobile phone manufactures commonly ignorant of the vision-impairment difficulty with operating mobile phone user interfaces; (2) The vision-impairment preferential with audio alert signals; (3) The vision-impairment incapable of mobile-phone procurement independently unless with assistance from others; (4) Preferential with adding touch-usage interface design by the vision-impairment; in contrast with the least requirement for such functions as braille, enlarging keystroke size and diversifying-function control panel. With exploring the vision-impairment's necessary improvements and obstacles for mobile phone interface operation, this research is established with goals for offering reference possibly applied in electronic appliance design and . Hopefully, the analysis results of this research could be used as data references for designing electronic and high-tech products and promoting more usage convenience for those vision-impaired. PMID- 22317457 TI - Comparison of randomized and non-randomized controlled trials evidence regarding the effectiveness of workplace exercise on musculoskeletal pain control. AB - Evidence synthesized based on randomized controlled trials (RCT) results are recognized as the pinnacle of research excellence; however, the conduction of RCT in workplace environment is not always possible. This study comparatively reviewed evidence from RCT and non-RCT studies in which participants performed workplace exercise for musculoskeletal pain control. Up to February 2011, PubMed, MEDLINE, Embase, Cochrane, PEDro and Web of Science databases were searched. All trials that evaluated workplace exercise interventions for controlling musculoskeletal pain were included. The PEDro scale was used to rate the studies' quality, PRISMA and Cochrane recommendations were applied, and association between frequencies of effect size categories (small, moderate, large) from various outcomes by study type was tested (2x3 contingency table). The search yielded 10239 references in English, from which 21 RCT and 12 non-RCT were selected. Both groups of studies presented methodological flaws including descriptions of randomization, blinding of examiners and absence of intention-to treat analysis for the RCT, and further absence of controls and blind assessor for the non-RCTs. RCTs had significantly more moderate and large effect size reported in their results compared to non-RCTs (p=0.04). Considering the difficulties in randomizing participants in occupational settings, all studies would benefit from better describing pertinent methodological information. PMID- 22317458 TI - Teaching ergonomics to undergraduate physical therapy students: new methodologies and impressions of a Brazilian experience. AB - Being ergonomics a scientific discipline based on knowledge of several areas, it is important to use education methodologies that promote critical thinking and reflective during the educational process. The article discusses the importance of interdisciplinarity in undergraduate courses in health care in particular in disciplines that address the ergonomics issue. The aspects of the introduction of new education methodologies, as well as case studies in undergraduate courses in Brazil, are discussed in this study. Based on the literature review conducted, some proposals for action in the interdisciplinary teaching of ergonomics in Physiotherapy courses are presented. PMID- 22317459 TI - Postural analysis and psychosocial measurements of federal civil servants of an institution of higher education. AB - The aim was to evaluate work engagement (WE), ratings of perceived exertion (RPE), postural deviations and to characterize musculoskeletal symptoms of federal civil servants of an institution of higher education. METHODS: Twenty four women (age 40.0 +/- 11.2 years, 1.6 +/- 0.1m, 66.6 kg +/- 10.0 kg) and 13 men (age 38.3 +/- 10.3 years, 1.7 +/- 0.1m, 84.3 kg +/- 19.1 kg) were recruited. The Nordic Questionnaire was used to evaluate musculoskeletal symptoms and the Borg Scale for the RPE. WE was quantified by the Utrecht Work Engagement Scale (vigor, dedication and absorption domains). Posture was assessed by photogrammetry and analyzed with the Postural Assessment Software (PAS/SAPO). The independent student t test was used to verify WE and postural differences and the chi-square test to verify RPE and symptoms' differences between genders. RESULTS: All subjects reported musculoskeletal complaints, mainly in the low back (28.4%). Women presented more musculoskeletal complaints (67%). RPE and WE did not differ between genders, however, women presented pronounced postural deviations compared to men (angle between leg and right foot dorsum, and horizontal pelvic alignment; p<0.05). CONCLUSION: Findings highlight the implementation of health promotion measures, such as postural reeducation and ergonomic guidelines, with specific activities according to gender. PMID- 22317460 TI - Musculoskeletal disorders and psychosocial risk factors among workers of the aircraft maintenance industry. AB - During the recent decades Brazil has experienced an exponential growth in the aviation sector resulting in an increasing workforce. The aircraft maintenance industry stands out, where the workers have to handle different kind of objects. The aim of this study was to evaluate psychosocial indicators as well as musculoskeletal symptoms and disorders among aircraft maintenance workers. One hundred and one employees were evaluated (32.69 +/- 8.25 yr, 79.8 +/- 13.4 kg, and 1.75 +/- 0.07 m). Musculoskeletal symptoms and disorders were assessed through the Nordic Musculoskeletal Questionnaire (NMQ) and a standardized physical examination. The Job Content Questionnaire (JCQ) and the Utrecht Work Engagement Scale (UWES) were applied to evaluate psychosocial indicators. Results of the NMQ indicate the lower back as the most affected body region. On the other hand, the physical examination has shown clinical diagnosis of shoulder disorders. Neck, upper back and ankle/foot were also reported as painful sites. Most of workers have active work-demand profile and high work engagement levels. We suggest that musculoskeletal symptoms may be related to high biomechanical demand of the tasks performed by workers, what must be further investigated. PMID- 22317461 TI - Are cutout handles used when available in real occupational settings? Description of grips and upper extremities movements during industrial box handling. AB - In order to achieve better postures and decrease musculoskeletal risks adequate design of hand/box couplings for manual materials handling (MMH) are still needed. No studies evaluating upper limb movement thorough direct measurements during box handling in workplace were identified in the literature. In this study we describe the types of grip and movements adopted by ten workers when handling redesigned boxes with cutout handles between different heights on industrial pallets. The new handles were used by 90% of the workers through different types of grip. Electrogoniometric measurements showed relatively safe forearm and wrist movements, although elbow inadequate range of movement was recorded. Despite the good acceptance of the cutout by workers, the new design requires extra internal space in the boxes reducing applications for this alternative of box. PMID- 22317462 TI - The influence of the tasks characteristics in physical performance and psychosocial aspects of workers. AB - The work and life conditions have influence on the health and life quality of workers. Physically active persons can demonstrate a life style that are and affect the physical performance, psychosocial aspects and work capacity. The purpose of this study was to investigate the physical activity level and work capacity in different tasks characteristics, one with more physical exertion and other with more cognitive exertion. A total of 193 workers from an institution of higher education and 457 workers from a metallurgical industry participated in the current study. All participants completed the International Physical Activity Questionnaire (IPAQ-short) and Work Ability Index (WAI). The results indicated that both groups were classified as having high level of physical activity while only few of them were considered sedentary (less than 27%). However, the group of metallurgical workers had greater indices (82%) than the workers from higher education institution (74%). Overall, the workers reported their work ability as moderate to excellent, suggesting that overall they are satisfied with their working and health conditions. It can be concluded that even though workers performed tasks with different demands (cognitive versus physical), they demonstrated similar level of physical activity as well as work ability. PMID- 22317463 TI - Furniture dimensions and postural overload for schoolchildren's head, upper back and upper limbs. AB - The aim of this study was to evaluate how the fixed furniture dimensions match with students' anthropometry and to describe head, upper back and upper limbs postures and movements. Evaluation was performed in 48 students from a Brazilian state school. Furniture dimensions were measured with metric tape, movements and postures by inclinometers (Logger Tecknologi, Akarp, Sweden). Seat height was high for 21% and low for 36% of the students; seat length was short for 45% and long for 9% and table height was high for 53% and low for 28%. Regression analysis showed that seat/popliteal height quotient is explained by 90th percentile of upper back inclination (beta=0.410) and 90th percentile of right upper arm elevation (beta=-0.293). For seat/thigh length quotient the significant variables were 90th percentile of upper back velocity (beta=-0.282) and 90th percentile of right upper arm elevation (beta=0.410). This study showed a relationship between furniture mismatch and postural overload. When the seat height is low students increase upper back left inclination and right upper arm elevation; when the seat is short students decrease the upper back flexion velocity and increase right upper arm elevation. PMID- 22317464 TI - Influence of door handles design in effort perception: accessibility and usability. AB - The application of ergonomics in product design is essential to its accessibility and usability. The development of manual devices should be based on ergonomic principles. Effort perception analysis is an essential approach to understand the physical and subjective aspects of the interface. The objective of the present study was to analyze the effort perception during a simulated task with different door handles by Portuguese subjects of both genders and different ages. This transversal study agreed with ethical aspects. 180 subjects of both genders pertaining to three age groups have participated. Five door handles with different shapes were evaluated. A subjective numeric rating scale of 5 levels was used to evaluate the effort. For statistical analysis it was applied the Friedman non-parametric test. The results have showed no significant differences of effort perception in door handles "A" and "B"; "A" and "D"; and "D" and "C". Door handle "E" presented the lowest values of all. In general, there's an inverse relationship between the results of biomechanical studies and the effort perception of the same task activity. This shows that door handles design influence directly these two variables and can interfere in the accessibility and usability of these kinds of products. PMID- 22317465 TI - Brazilian version of an assessment tool for the evaluation of work organizational aspects (AOT) by the NIOSH WMSD Research Consortium: translation and application in industrial sectors. AB - Work organization affects the production of a company as well as the health of employees. It is a challenge to create sustainable production systems with the least harm to the health. An observational assessment tool was developed by the NIOSH--WMSD Research Consortium and adapted by the SHARP study. The objectives were to translate this assessment tool into Brazilian Portuguese (as the Avaliacao de Aspectos Organizacionais do Trabalho--AOT) and to evaluate its applicability in an industrial setting. The AOT final translated version was obtained after a consensus by the research team. Difficulties arose in applying the translated version due to technical terms with no direct equivalents in Portuguese, nonexcluding or similar alternatives, and questions that gave room for various interpretations, besides the great complexity of the tasks performed in the sectors. Despite that, the results suggest that AOT was sensitive for discriminating differences between sectors. Nevertheless, for better application of this tool in complex industrial environments, it is necessary: training and consensus among evaluators, familiarity with organizational aspects of the occupational settings evaluated. Also for assuring the internal validity of the analysis, might be necessary, the creation of subdivisions in the sectors evaluated if the tasks vary significantly intra-sector. The present report can help to understand the difficulties inherent to the evaluation of organizational aspects on a collective level and also the possible implications related to the translation of this assessment into other languages. PMID- 22317466 TI - Need for recovery assessment among nursing professionals and call center operators. AB - The present study descriptively compares the need for recovery (NFR) among 128 nursing professionals (nurses) and 223 call center operators according cutoff points in the literature (45 and 50) and by means of statistical tests, and verifies the association between NFR scores and the presence of musculoskeletal symptoms. NFR was evaluated with the Need for Recovery Scale and musculoskeletal symptoms were evaluated with the Nordic Musculoskeletal Questionnaire. At a 45 point cutoff, 22% of the call-center workers and 33% of the nurses were classified as fatigued; at a 50 point cutoff, 13% of the call center operators and 27% of the nurses were classified as fatigued. The nurses had higher fatigue levels than the call center workers (p=0.015). Significant correlations were found between NFR scores and musculoskeletal symptoms reported during the previous 12 months (r=0.299, p<0.001) and 7 days (r=0.314, p<0.001). Regarding cutoff points and statistical tests, the NFR scale identified higher fatigue levels among the nurses and was demonstrated to be a useful tool for evaluating worker well-being. PMID- 22317467 TI - Psychosocial risks: acting upon the organisation by ergonomic intervention. AB - In this paper we discuss the possibilities of acting on psychosocial risk (PSR) factors by modifying the way in which an organisation operates. On the basis of an ergonomic intervention in an insurance company, we were able to show that the health problems observed by the operators were mainly the result of their inability to produce work of quality. Next, our analyses revealed the links between poor perceived quality, production difficulties and the rigidity of the organisational structure. After setting up working groups to deal with production difficulties, we were able to identify and test an organisational form that was better adapted to managing day-to-day production constraints and which was ultimately better able to be attentive to individual difficulties which had given rise, in the long term, to intrapsychic conflicts. PMID- 22317468 TI - Outcome measures and prognosis of WRMSD. AB - Work Related Musculoskeletal Disorders (WRMSDs) are widespread in many countries, with substantial costs and impact on quality of life. WRMSDs create a significant financial burden to both employer and employee that includes the cost of treatment and lost work time. There is a growing demand to implement early identification and effective prevention strategies, aimed at early intervention in employees prior to possible absenteeism due to foreseen sickness or disability. Outcome measure of the WRMSD gives an understanding about the severity and the intensity of the problems. Before starting of the treatment it is very important to understand the gravity and seriousness of the WRMSD. Once we understand the gravity of the WRMSD the level of the treatment can be decided and optimum prescription can be made for that particular WRMSD. OBJECTIVES: This will discuss various outcome measures through which prognosis of the WRMSD can be determined and final prescription of treatment regiment can be formulated. PMID- 22317469 TI - Supervisors in ergonomic change of meat cutting work. AB - Being a supervisor is an important and lonely occupation. The aim of this study was to identify barriers and opportunities in working conditions for supervisors, being facilitators and implementers of change for meat cutters. Nine supervisors of meat cutters in one large company were interviewed. The semi-structured interviews covered their roles as supervisors, performance of the change process and their own working conditions. Notes were taken and structured in themes. Similarities, differences, plus and minus were identified. There was a nuanced view on the change processes and their effects. The change processes and the decisions were anchored in a democratic process with groups of employees and the union. All were clear on what demands the company had on them. They were secure in a functioning network of peers and their immediate superior. On their own education, most were as a whole satisfied, but in need of more training and talked of lifelong learning. They considered their work demanding and lonely, with a need both to be manager and leader. A shared leadership could mean doing a better job. There is a need for education and training as a manager and leader as well as the opportunity to discuss with peers. PMID- 22317470 TI - New ways of organizing product introductions. AB - The aim of this paper is to describe and reflect on an interactive research approach used to address the challenges on how to improve product introductions, the part of the product realization process associated with the transfer of a product from product development to serial production. In the interactive research approach, research results as well as improvement of practice are given equal importance. The collaboration between researchers and practitioners therefore addresses both the focus and the process of the change. The approach includes four main iterative steps: 1) mapping/diagnosis, 2) feedback of results, 3) participation in development activities, and 4) follow-up/evaluation. The paper reports findings from interactive research in one company within office product industry and one company group, consisting of three company units within the engine industry. Preliminary findings indicate that the participating companies afterwards work in a more structured way with product introductions and that the employees have gained deeper knowledge about product introductions as well as experienced the advantages of working across functional boundaries. Furthermore, the interactive research approach is suitable to run projects from an ergonomics perspective as it focuses on developing both practice and theory, it is human-centered, and it emphasizes broad participation from practitioners. PMID- 22317471 TI - Ten years of experience from interactive ergonomics projects. AB - This paper highlights experiences from ergonomics projects, applying an interactive research approach. The aim of this paper is to summarise experiences from seven interactive ergonomics projects with the aim to improve ergonomics and organizational performance jointly. Results from these seven projects were analysed with a model for assessing sustainable change, including the factors active ownership, professional management, competent project leadership, and involved participants. All factors were found giving support to impact and sustainability of the change projects. However, the role of the researcher is difficult and demanding. PMID- 22317472 TI - Decision support for vessel traffic service (VTS): user needs for dynamic risk management in the VTS. AB - Vessel Traffic Service (VTS) is a shore-side service implemented by a "Competent Authority to improve the safety and efficiency of vessel traffic and to protect the environment". It is a service that operates through VTS centers, from which VTS operators monitor traffic, assist in navigational matters and provide information to all ships in a designated area. As VTS is provided by operators located on shore, they usually make use of several decision support systems to be able to monitor the traffic and to provide information to the vessels. Although several new tools and approaches have been introduced in the VTS domain, there is still room for improvements. This paper summarizes the results from three studies conducted within the EfficienSea project to approach user needs for dynamic risk management in the VTS domain. Data was collected by conducting study visits and observations at VTS centers, a focus group interview as well as several semi structured interviews. The paper summarizes the results and presents technical and organizational user needs for dynamic risk management within the VTS domain. PMID- 22317473 TI - Transmitting intended and suggested routes in ship operations: cognitive off loading by placing knowledge in the world. AB - Transmission of intended and suggested routes to and from electronic chart systems has been identified as a user need. The idea was discussed during a focus group meeting and two field studies in fringe fields like search and rescue (SAR) and ice breaking. A prototype test was then conducted during a SAR drill. The features were very well received by all the participants in the drill. A system simulation with two ships and a VTS station was also conducted in a full mission bridge simulator. Preliminary results are very promising. Behavior with vessels in conflicting situations suggested that the intended routes could facilitate understanding when negotiating with or without VHF communication. No major concerns were expressed by the professional crew members that participated. PMID- 22317474 TI - New insights, new challenges; person centred transport design. AB - This paper uses the Hexagon Spindle model of ergonomics to provide a framework for the development of person centred approaches to vehicle and transport design. The benefits of taking this approach, and the factors that might be included under a more inclusive definition of automotive and Transport ergonomics are explained. PMID- 22317475 TI - From the "terrain" to "territory": which contributions from mobility and bus drivers' activity towards local development? AB - The focus of the present analysis is on the work of drivers in the public road passenger transportation sector in Portugal and on its specific contribution to local development. This approach dissociates itself from the one that places mobility as a "paradigm" of the contemporary societies and considers that the increase in mobility registered in the latter years is, in itself, revealing of development. For field work, a public transportation line, in an urban context, and a network of lines, in a rural context were chosen. In each of these contexts, the drivers' work was analyzed in real situations and semi-structured interviews were held with 16 of them: ten drivers in an urban context and six in a rural context. Considering the point of view of the work activity, enabled us to abandon the dominant perspectives that tend to highlight the social inequality of the mobility conditions (between those who use a private vehicle and those who need to use public transportation), to reflect on the characteristics of the mobility spaces which benefit or limit it, contributing to other inequalities. What is the importance of the space for mobility besides its support? How is it considered in the drivers' work? PMID- 22317476 TI - Ergonomic investigation on pedestrian crossing with traffic light signalization. AB - This article is about the risk behavior adopted by pedestrians at crosswalks with traffic light equipment. It was observed that many pedestrians take risk to cross the Presidente Vargas Avenue. This avenue is located in downtown in Rio de Janeiro city, Brazil, and has a heavy vehicular traffic and intense pedestrian flow. Many pedestrians cross the four lanes of avenue dangerously disobeying the traffic light indications. To conduct this research about pedestrian's behavior at crosswalks, a model known as Communication-Human Information Processing Model C-HIP Model was used. Investigating the stages by C-HIP model perspective, using methods and techniques for each stage, enabled to identify which factors can contribute to pedestrians to disobey traffic signs and adopt a risky behavior in pedestrian crossing. PMID- 22317477 TI - What does a motorcyclist look at while driving at urban arterials? AB - To design adequate measures for enhancing riders' safety, a necessary first step is to understand the riders' visual scanning strategies under different traffic conditions. This paper presents the preliminary analysis of eye tracking data collected by three riders in the Athens metropolitan area, riding along urban arterial motorways and along an undivided urban road. Apart from the fixation duration and location, the fixated road elements and specific objects were annotated and analysed. The mean duration of fixations was found to be higher on urban roads than on motorways for all traffic densities. Riding in the condition of restricted flow seems to be more demanding for the riders, since the mean duration of fixations was higher in restricted flow than in free or congested flow on motorway and also higher than in free flow on urban road. The riders' fixation locations differed between motorway and urban road, especially in the vertical plane. The analysis of fixated road elements and specific objects indicates the specific points of interest of riders in each case. Although results should be validated with data from more riders, they provide hints on direction of future research efforts to enhance riders' safety in urban environments. PMID- 22317478 TI - Skills of novices early trained or traditionaly trained versus experienced drivers confronted to simulated urban accidents' scenarios. AB - In order to prevent the over-representation of young drivers in car crashes, France instated an early driver training from the age of 16, but the positive effects of this opportunity have not yet been proven. Three groups of male drivers (12 subjects each) were confronted with some prototypical accident scenarios introduced in a simulated urban circuit. The first and second groups were composed of young drivers having less than one month of driving licence; twelve have had a traditional learning course, and twelve had followed, in addition to the initial course, an early driver training under the supervision of an adult. The third group was composed of experienced drivers. Strategies of the three groups were analyzed through their response time, speed and maneuvers. No difference appeared across groups regarding obstacle detection. But traditionally trained drivers' position control was more conservative than the two others groups, which were more likely to involve efficient evasive action. The exposure gained during early training could thus increase the development of visuo-motor coordination and involve better skills in case of difficult situations. Others accidents' scenarios could be used to confront young drivers with difficult situations not commonly encountered in natural driving. PMID- 22317479 TI - Factors and motives of unsafe behaviors of road users. AB - A questionnaire to measure factors and motives of unsafe behaviors of road users was constructed. This study tool was applied on a final sample of 5586 drivers in twelve out of forty eight districts in Algeria. The aim of the present study was to sort out the different factors and motives that make road users opt for the unsafe behaviors. The latter were determined mainly on the results of a previous study carried out on a final sample of 7058 drivers in twelve out of forty eight districts in Algeria in order to find the most frequent and dangerous unsafe behaviors of road users. The main unsafe and dangerous behaviors were then used in the present study. Friedman ranking means test was applied to rank the factors and motives selected under each unsafe behavior of road users. The whole results were summarised in seven axes of factors and motives causing: dangerous manoeuvrings by drivers, aggressive behaviors by drivers, negligence and ignorance of maintenance principals by drivers, lack of responsibility and engagement by drivers, cyclists and motorcyclists and their companions, as well as pedestrians and workers of road maintenance. The results are discussed in view of the previous studies and many recommendations have been made. PMID- 22317480 TI - Assessment of cognitive workload of in-vehicle systems using a visual peripheral and tactile detection task setting. AB - The increase of driver information and infotainment systems includes also interaction technologies like speech interaction that minimize visual-manual demand and put the focus to cognitive demand. The question is whether this could lead to distraction effects and decreased traffic safety. This study presents an evaluation method for cognitive demand based on different detection paradigms in a dual task setting. A listening and a backward counting task are realized on three difficulty levels as simulations of cognitively loading secondary tasks and investigated using a visual versus a tactile detection paradigm. The results show that both detection paradigms are able to discriminate the task levels and that subjects successfully apply compensation strategies in the dual task setting especially during the listening task. PMID- 22317481 TI - Ergonomic evaluation of a wheelchair transportation securement system. AB - The Americans with Disabilities Act (ADA) specifies guidelines covering the securement system and environment for wheeled mobility device (WhMD) passengers on the public bus system in the United States, referred to as the wheelchair tiedown and occupant restraint system (WTORS). The misuse or disuse of the WTORS system can be a source of injury for WhMD passengers riding the buses. The purpose of this study was to quantify the risks posed to the bus driver while performing the WTORS procedure using traditional ergonomic analysis methods. Four bus drivers completed the WTORS procedure for a representative passenger seated in three different WhMDs: manual wheelchair (MWC), scooter (SCTR), and power wheelchair (PWC). Potential work-related risks were identified using the four most applicable ergonomic assessment tools: PLIBEL, RULA, REBA, and iLMM. Task evaluation results revealed high levels of risk to be present to drivers during the WTORS procedure. The securement station space design and equipment layout were identified as contributing factors forcing drivers to adopt awkward postures while performing the WTORS task. These risk factors are known contributors to injury and the drivers could opt to improperly secure the passengers to avoid that risk. PMID- 22317482 TI - Aircraft accident investigation: the decision-making in initial action scenario. AB - In the complex aeronautical environment, the efforts in terms of operational safety involve the adoption of proactive and reactive measures. The process of investigation begins right after the occurrence of the aeronautical accident, through the initial action. Thus, it is in the crisis scenario, that the person responsible for the initial action makes decisions and gathers the necessary information for the subsequent phases of the investigation process. Within this scenario, which is a natural environment, researches have shown the fragility of rational models of decision making. The theoretical perspective of naturalistic decision making constitutes a breakthrough in the understanding of decision problems demanded by real world. The proposal of this study was to verify if the initial action, after the occurrence of an accident, and the decision-making strategies, used by the investigators responsible for this activity, are characteristic of the naturalistic decision making theoretical approach. To attend the proposed objective a descriptive research was undertaken with a sample of professionals that work in this activity. The data collected through individual interviews were analyzed and the results demonstrated that the initial action environment, which includes restricted time, dynamic conditions, the presence of multiple actors, stress and insufficient information is characteristic of the naturalistic decision making. They also demonstrated that, when the investigators make their decisions, they use their experience and the mental simulation, intuition, improvisation, metaphors and analogues cases, as strategies, all of them related to the naturalistic approach of decision making, in order to satisfy the needs of the situation and reach the objectives of the initial action in the accident scenario. PMID- 22317483 TI - Aircraft seating comfort: the influence of seat pitch on passengers' well-being. AB - One of the most important factors influencing aircraft seating comfort in economy class, is legroom. In an airline interior mock up, with the ability to adjust the seat pitch in a range of 28 inches to 43 inches, a study to investigate the influence of seat pitch on passengers' well-being was conducted. In a pre-study, aspects of subjective postural sensations and spatial perception were identified, and a questionnaire was developed. In the main study, 30 subjects rated at different seat pitch settings the spatial perception and the ability of adopting and changing sitting postures. As a result a functional relationship between overall well-being, the subjects' anthropometry and seat pitch was developed. Furthermore it was identified, that there is a maximum overall well-being at a seat pitch of 34 inches to 40 inches, depending on the passengers' anthropometry. A further enlargement of seat pitch, led to a reduction of well-being. PMID- 22317484 TI - Research of injuries of passengers in city buses as a consequence of non collision effects. AB - In this study, a research of injuries of passengers in city buses is presented, which are not a consequence of collision of buses with other objects. The number of injured passengers in the territory of Belgrade was registered, during three consecutive years. Most frequently injured body part was the head, while women over the age of 60 are the most vulnerable population of passengers. The most often reason for the appearance of injuries was the effect of acceleration. Also, it is pointed out to the importance of consideration of the problem of multiple injuries. These injuries are more complex than the individual ones, and they may indicate to the existence of greater omissions in the design of the interior of the bus. Proposals for certain system solutions, as well as some recommendations for designing are given, which can improve the safety of passengers who use the city bus as a means of transportation. PMID- 22317485 TI - Low-floor bus design preferences of walking aid users during simulated boarding and alighting. AB - Low-floor buses represent a significant improvement in accessible public transit for passengers with limited mobility. However, there is still a need for research on the inclusive design of transit buses to identify specific low-floor bus design conditions that are either particularly accommodating or challenging for passengers with functional and mobility impairments. These include doorway locations, seating configuration and the large front wheel-well covers that collectively impact boarding, alighting and interior movement of passengers. Findings from a laboratory study using a static full-scale simulation of a lowfloor bus to evaluate the impact of seating configuration and crowding on interior movement and accessibility for individuals with and without walking aids are presented (n=41). Simulated bus journeys that included boarding, fare payment, seating, and alighting were performed. Results from video observations and subjective assessments showed differences in boarding and alighting performance and users' perceptions of task difficulty. The need for assistive design features (e.g. handholds, stanchions), legroom and stowage space for walking aids was evident. These results demonstrate that specific design conditions in low-floor buses can significantly impact design preference among those who use walking aids. Consideration of ergonomics and inclusive design can therefore be used to improve the design of low-floor buses. PMID- 22317486 TI - Ergonomic factors and production target evaluation in eucalyptus timber harvesting operations in mountainous terrains. AB - There are several forest operations involved in Eucalyptus timber harvesting. This study was carried out during brush-cutting; tree felling, bucking, delimbing, piling and manual extraction operations, with the following objectives: a) analyzing, ergonomically, two systems of brush-cutting: one manual and the other semi-mechanized, using two different machines; b) ergonomically evaluating three different brands of pruner machines used in delimbing felled trees. c) determining the feasible target of productivity as a function of ergonomic factors relevant to establish the time of resting pauses for workers in manual and semi-mechanized timber harvesting systems in mountainous terrain. Brush-cutting, either manual or semimechanized, is an activity carried out prior to timber harvesting. It is usually a hard work, with low productivity when compared with mechanized systems. Pruner machines have been used by forest companies, due to the great possibilities to improve productivity, quality and the health of workers. Ergonomics is a discipline that promotes the adequacy of work to the physical and mental characteristics of human beings, seeking to design production systems and products considering relevant aspects, including social, organizational and environmental factors. Companies should consider the ergonomic factor in the determination of daily worker production targets. PMID- 22317487 TI - Protective gloves on manual sugar cane cutting are really effective? AB - Problems related to the use of personal protective equipment (PPE), specially the use of protective gloves for the manual sugar cane cutting, motivated this research, made possible by a tripartite negotiation involving the Ministry of Labor, the Union of Rural Workers and the Employer's Association of sugarcane agribusiness. The main objective was to evaluate, from an ergonomics perspective, the impact of use of the gloves during the manual cane sugar cutting, raising questions on safety, effectiveness and comfort. The research was carried in a sugarcane industry of Sao Paulo for two seasons involving 47 workers who made a qualitative analysis of acceptance of four models of protective gloves. The methodology included the use of semi-structured interviews, questionnaires and field observations and the experimental determination of the coefficient of static friction developed between the gloves and the surfaces of the machete handle. The main results indicate the general inadequacy of the gloves currently used forcing the employees to improvise. Workers found the glove of leather and nylon scraping the best reported for comfort in use. The overall results highlight the problem of detachment of test standards for the manufacture of PPE, ignoring users and the activity to be performed. PMID- 22317488 TI - Impacts of introducing a new tool for the manual harvesting of sugar cane: the ergonomic analysis contribution. AB - The purpose of this study was to evaluate the impact of introduction a new work tool on health and productivity of manual harvesting sugarcane workers. In this study it was performed aErgonomic Work Analysis (EWA) to analyze the work tool changes.The study included sugarcane workers, drivers, fiscals, and technical's safety at work.During the analysis process, 134 questionnaires were applied,aimed to identify the constraints that such workers are submitted,to evaluate the tool introduced, in order to propose modifications to improve it.The results showed a decrease in perceived exertion and discomfort, without compromising the cut quality. The main contributions of Ergonomic Work Analysis were the possibility of bringing the logic of the worker, in order to understand the inherent real work characteristics, to the process of developing the new tool. Besides, it was also noted that this methodology, based on the analysis workers activity in a real usage, as an application tool in design projects, providing innovations from the workers perspective. PMID- 22317489 TI - A randomized intervention trial to reduce mechanical exposures in the Colombian flower industry. AB - Evidence on the effectiveness of ergonomic interventions to reduce mechanical demands and upper-extremity MSDs is scarce in agriculture. We conducted an intervention to reduce mechanical exposures during manual flower cutting through job rotation, education and reduction of force requirements. One-hundred and twenty workers (20 to 60 years old; 89% women) from six companies that cultivate roses participated in this study. Three companies were randomly assigned to control and intervention groups. We studied changes between baseline and follow up in self-reported effort and upper-extremity postures, kinematics and muscular activity. Most of the observed changes were moderate for both groups. The intervention group showed differential improvements compared to the control group for the maximum wrist radial deviation and forearm pronation, and acceleration of the forearm supination-pronation and elbow flexion-extension; and the muscular activity of the flexor and extensor carpi radialis and the flexor carpi ulnaris. However, we also observed that the maximum ulnar deviation, velocity of the wrist flexion-extension and muscular activity of the extensor carpi ulnaris improved more in the control group. These mixed results may be related to limited time for intervention adjustment, and uncontrolled task changes in the control group. Future research should address these issues and test other solutions. PMID- 22317490 TI - Work and technological innovation in organic agriculture. AB - Organic agriculture is a sustainable cultivation ecologically, economically and socially. Several researches in organic agriculture have been made from technical perspectives, economic traits or related to ecological aspects. There are practically no investigations into the nature of the technology used in organic agriculture, especially from an ergonomic perspective. From the activity analysis, this study aimed to map the technology used in the production of organic vegetables. Properties producing organic vegetables were selected representing the State of Sao Paulo. It was applied an instrument (questionnaire and semi-structured interview) with their managers and it was made visual records to identify adaptations, innovations and technological demands that simultaneously minimize the workload and the difficulties in performing the tasks and increase work productivity. For some of the technological innovations a digital scanner was used to generate a virtual solid model to facilitate its redesign and virtual prototyping. The main results show that organic farmers have little technology in product form. The main innovations that enable competitive advantage or allow higher labor productivity occur in the form of processes, organization and marketing. PMID- 22317491 TI - Thermal comfort and personal protective equipment (PPE). AB - Personal Protective Equipment (PPE) is considered the last preferred solution to an Occupational Safety Health (OSH) system. Brazilian OSH legislation assumes and requires PPE usage to neutralize the possibility of pesticide contamination. This study examines the inadequacy of the PPE used in a tomato crop, particularly from the standpoint of thermal comfort. This study made observations regarding heart rate and body temperature in a controlled environment using a treadmill (with and without PPE) of 12 volunteers; and during the process of rural labor (at rest and in normal work routine) of 2 actual rural workers. Comparing the results of the treadmill test (with and without PPE) which tried to reproduce the same level of effort and environmental conditions of the actual rural work, this study demonstrated that PPE makes thermoregulation harder and tympanic temperature reaches higher values with the same level of effort. Moreover, body temperature increases quickly: with PPE it took 15 minutes to raise 1 degrees C in body temperature, compared to 40 minutes without PPE. The results of this study indicated that the use inadequate PPE might pose thermoregulation risk to rural workers. PMID- 22317492 TI - Occupational health hazards & efficacy of protective masks in threshing operation. AB - The study was conducted on 20 farm workers to identify the occupational health hazards in threshing operation. Four different protective masks were given and tested on various parameters. Respondents reported respiratory health problems which were mainly due to heat and organic dust in the surroundings. All respondents reported irritation in eyes and throat followed by nose (85.0%) and ears (75.0%). Musculo-skeletal problems were reported showing severe to very severe discomfort in lower arms (m.s. = 3.8), upper back (3.6) and upper arms (3.4). Overall discomfort score (ODS) was 7.6 depicting high level of discomfort. Peak expiratory flow rate was reduced by 6.6 % depicting reduced capacity of lungs after day long work in polluted environment. Hood mask was highly acceptable as it showed lowest breathing resistance. Leakage of dust from sides and rate of sweating was medium. Hence, use of hood mask would be helpful to achieve the ergonomics objective of reducing health problems and improving performance. PMID- 22317493 TI - Family farming workers mental health in a microrregion in southern Brazil. AB - This research aims at investigating family farming workers' of Ituporanga microregion mental health problems and sociodemographical feature and work process association. The sample corresponded to 447 family farming workers in Ituporanga, i. e., part of the overall population lives in the 1.578 rural properties of the city (IBGE, 2007). A questionnaire with socio-demographic and work process variables was used for data collection concerning mental health problems along with the Self Report Questionnaire (SRQ-20). Inference descriptive statistics with central trend measures and variability was used for data analysis. By means of binary logistic regression the probability of an event, i.e. the presence of mental health problems occur as a result of predicting variables. Level of significance 5% was adopted in all statistical procedures. The investigation revealed the prevalence of 33,8% of mental health problems. It was observed that women prevailed with 39,7% (n = 91), in contrast with men with 26,1% (n = 46), being such association statistically significant (X2 = 8,225, df = 1, p = 0,004, phi= -0,143). Socio-demographical and work process variables showed predictors of mental health problems, such as: (sex, age, use of agrochemicals, working hours outside and during harvest time, being family intoxication the most important. Mental health problems showed mostly associated to the use of agro-chemicals and farmers being intoxicated. PMID- 22317494 TI - Pesticide exposure and sprayer's task goals: comparison between vineyards and greenhouses. AB - Plant protection products are used in agriculture to improve yields, but this use can cause contamination of the environment and is also likely to have adverse short and long term effects on agricultural workers. The field study took place in greenhouses and vineyards where operators are involved in high levels of pesticide spraying. The objective of this intervention was to identify factors explaining the influence of task factors on the exposure of greenhouse growers and vineyard workers. Thirteen operators were selected for detailed observations during one session of spraying. Video recordings provide counts of physical contacts between the operator and all the surrounding surfaces during the spraying operation. Both in vineyards and in greenhouses, physical and temporal constraints are the predominant factors in establishing a specific spraying procedure. Every action taken by the operator is a result of a compromise between safety, task performance and quality. PMID- 22317495 TI - Intervention of drudgery reducing technologies in agriculture and impact evaluation. AB - Agriculture is main source of livelihood for majority of the population in India. Agriculture has been established as one of the drudgery prone occupation of unorganized sector due to lack of access to improved agricultural technologies. The present study was planned to assess intervention of drudgery reducing technologies in agriculture and its impact evaluation. The drudgery areas/activities in agriculture were identified. Participatory field level skill training for proper use of the ergonomically improved farm technologies were given to men and women in separate groups. An intervention package consisting of improved sickle, wheel hand hoe, capron, cot bag and protective gloves was introduced in village Shahpur. Data were collected to quantify the impact of intervention on the level of drudgery of worker before and after the technology intervention from sample of 30 respondents (15 male and 15 female) selected randomly from village Shahpur. Gain in knowledge and change in awareness level were calculated after the training.Evaluation of field validation of technology on drudgery of men & women was done after its use in the field conditions. A significant gain in awareness was observed among both men(2.6) & women (3.0) whereas the gain in knowledge was more among men (6.6) than women (4.5). In evaluation of field validation of technology on drudgery it was found that all the five technologies reduced the drudgery of men as well as women. However wheel hand hoe was used successfully by men in comparison to women who preferred to use their conventional technology i.e improved long-handled hoe. Evaluation of validation trials of the technologies reported that improved sickle was used successfully by both men & women farmers. More than half of the men farmers (53.3%) & only 13.3 percent women farmers preferred the wheel hand hoe over the traditional one as they found it four times more efficient in terms of time, energy & money saving. Cot bag was preferred by the entire sample. Capron was preferred by four-fifth of the men farmers (80.0%) whereas women farmers did not prefer it much. Only one third of men (33.3%) & 26.7 percent of women farmers preferred using gloves while harvesting of guar & picking of cotton. PMID- 22317496 TI - Innovation - decision behaviour of tribal women of Udaipur district regarding vermiculture technology. PMID- 22317497 TI - Usability study of a vineyard teleoperated compost spreader. AB - Teleoperation has been widely applied in modern industry because of a variety of advantages, such as providing replaceable surrogates for humans in dangerous or difficult working environments over long distances. In this paper, a usability evaluation study of a teleoperation system for a compost spreader robotic machine is presented. The machine has been designed for the application of compost in small and stepping parcels of hilly vineyards. Driving and working tasks can be controlled remotely by a portable piloting unit, reducing the risk for the operator in the event of machine overturning. Participants of the study were asked to perform a series of tasks and sub-tasks and to vocalize their thoughts while working with the machine. The tasks were designed to simulate typical user experience. Once all the tasks were accomplished each participant was asked to fill a questionnaire. The evaluation considered aspects such as learnability, ease of use, understandability, controllability, frustration, mental effort, distraction, clarity of presentation, perceived usefulness, temporal efficiency and machine aesthetic. Results show that usability evaluation helped detecting design deficiencies in the teleoperated compost spreader machine. PMID- 22317498 TI - An ergonomics approach to citrus harvest mechanization. AB - Due to the increase of production costs in manual harvesting, strategies must be developed in order to overcome these effects, such as the attempts in implementing agricultural machines in harvest activities, whether being totally or partially mechanized. This study brings a qualitative and quantitative comparison on the impacts in work conditions and productivity in Brazilian orchards caused by the use of semi-mechanized harvesting systems, such as multiplatforms. The results come from the application of Ergonomic Work Analysis method, which focuses in the activity, quantifying and analyzing times and frequencies of the harvesting cycle, as well as the amount of movements. To achieve this, footage, interviews and a stopwatch were used in the observation 12 pickers' work cycles, six for each method of harvesting. The data interpretation pointed to improvement in working conditions with a reduction in the amount of movements performed by the picker, and increase of up to 60% in productivity with the use of semi-mechanized harvesting. Thus, the found results indicate the viability of this harvesting method. However, other variables must be observed in future studies in order to complete the guidelines for a healthy progress in the area of citrus harvesting in Brazil. PMID- 22317499 TI - The recent history of the IEA: an analysis of IEA Congress presentations since 1961. AB - In this paper we review historical material relating to the growth and coverage of past IEA meetings and congresses. In particular, we report on presentations at IEA Congresses dating back to the first one in Stockholm in 1961. A content analysis of Congress proceedings was carried out and we present findings on changes since 1961 covering: numbers and nationalities of conference participants and the types of topics presented at Congresses. Our findings point to evidence of widening participation at the conferences, in particular delegates drawn from Asia, South East Asia and the Far East. In addition, some topics (e.g., physiology, methodological papers and studies of workload) appear to have waned in popularity over the period, whereas some topics (e.g., ODAM, Cognitive Ergonomics) have grown in popularity. We discuss these findings in the light of other evidence covering historical trends and developments within human factors and ergonomics. PMID- 22317500 TI - Emerging role of human factors and ergonomics in healthcare delivery - a new field of application and influence for the IEA. AB - Recent developments of research and application of Human Factors and Ergonomics (HFE) are described, in particular the domain of healthcare delivery. HFE activities in this domain are highlighted and challenges for the discipline and the International Ergonomics Association are presented. PMID- 22317501 TI - Recurring issues in the IEA, the discipline and the profession of ergonomics/human factors. AB - Although the past 25 years have seen many apparently new challenges for the academic discipline and the professional practice of ergonomics/human factors, and for the International Ergonomics Association, many issues in fact have recurred over the period. This paper takes the relevant decades and de3scribes the internal and external priorities of the IEA at the time, the main developments for researchers and practitioners, and the author's own professional interests at the time..Such an admittedly partial description of events and priorities could feed into current attempts to strengthen the position of ergonomics/ human factors for this and subsequent decades. PMID- 22317502 TI - Using naturalistic driving films as a design tool for investigating driver requirements in HMI design for ADAS. AB - In recent years, there are many naturalistic driving projects have been conducted, such as the 100-Car Project (Naturalistic Driving study in United State), EuroFOT(European Large-Scale Field Operational Tests on Vehicle Systems), SeMi- FOT(Sweden Michigan Naturalistic Field Operational Test and etc. However, those valuable naturalistic driving data hasn't been applied into Human-machine Interaction (HMI) design for Advanced Driver Assistance Systems (ADAS), a good HMI design for ADAS requires a deep understanding of drive environment and the interactions between the driving car and other road users in different situations. The results demonstrated the benefits of using naturalistic driving films as a mean for enhancing focus group discussion for better understanding driver's needs and traffic environment constraints. It provided an efficient tool for designers to have inside knowledge about drive and the needs for information presentation; The recommendations for how to apply this method is discussed in the paper. PMID- 22317503 TI - Methodical aspects of text testing in a driving simulator. AB - A test with 30 test persons was conducted in a driving simulator. The test was a concept exploration and comparison of existing user interaction technologies for text message handling with focus on traffic safety and experience (technology familiarity and learning effects). Focus was put on methodical aspects how to measure and how to analyze the data. Results show difficulties with the eye tracking system (calibration etc.) per se, and also include the subsequent raw data preparation. The physical setup in the car where found important for the test completion. PMID- 22317504 TI - The use of affective interaction design in car user interfaces. AB - Recent developments in the car industry have put Human Machine Interfaces under the spotlight. Developing gratifying human-car interactions has become one of the more prominent areas that car manufacturers want to invest in. However, concepts like emotional design remain foreign to the industry. In this study 12 experts on the field of automobile HMI design were interviewed in order to investigate their needs and opinions of emotional design. Results show that emotional design has yet to be introduced for this context of use. Designers need a tool customized for the intricacies of the car HMI field that can provide them with support and guidance so that they can create emotionally attractive experiences for drivers and passengers alike. PMID- 22317505 TI - Countermeasure drowsiness by design - using common behaviour. AB - This study takes a starting point in what drivers do to avoid drowsiness while driving instead of starting with what researchers know is efficient (Take a short nap). It is concluded that research is missing when it comes to how efficient common behavior countermeasures are and that there is a mismatch between research and how people actually behave. A three stage approach which includes identification, information and countermeasure is suggested. Furthermore are a few ideas of what car manufacturers can do to support human behavior presented. PMID- 22317506 TI - Towards a model to interpret driver behaviour in terms of mismatch between real world complexity and invested effort. AB - Driving behaviour has been less documented than driver workload. The possibilities to define a framework that could be part of a driving behaviour model were investigated. The results present a framework that defines twelve scenarios in which drivers have misinterpreted a driving situation. The descriptions show evidence of increased user experience for some scenarios while other indicates reduced traffic safety. The results suggest that by using the framework-descriptions on how and why mismatches occur, design guidelines for in vehicle systems can be developed. PMID- 22317507 TI - New ways of working: does flexibility in time and location of work change work behavior and affect business outcomes? AB - In the changing modern economy some new factors have been addressed that are of importance for productivity and economic growth, such as human skills, workplace organization, information and communication technologies (ICT) and knowledge sharing. An increasing number of companies and organizations are implementing measures to better address these factors, often referred to as 'the New Ways of Working (NWW)'. This consists of a large variety of measures that enable flexibility in the time and location of work. Expectations of these measures are often high, such as a reduction in operating costs and an increase of productivity. However, scientific proof is still lacking, and it is worth asking whether al these implementations actually cause a change in work behavior and effect business outcomes positively. This article describes a case study of three departments (total of 73 employees) that changed from a traditional way of working towards a new way of working. Questionnaires and a new developed objective measurement system called 'work@task' were used to measure changes in work behavior (i.e. increased variation in work location, work times and a change towards NWW management style) and the effect on business objectives such as knowledge sharing, employees satisfaction, and collaboration. PMID- 22317508 TI - The effects of new ways of work in the Netherlands: national data and a case study. AB - In 2010 15.2% of the work force in the Netherlands works with a computer at another location than at the office or at the clients' location. 27% of the Dutch working population is not satisfied about the possibility to work at home and 18% is not satisfied on the possibility to plan your own working time. The case control study affirms what has been reported as effects of new ways of work: the experienced productivity by communication and the representativeness of the office interior are improved and attention is needed for workers that need concentration space and need to personalize their work environment. In implementing new ways of work these issues need attention. PMID- 22317509 TI - Examining new ways of office work between the Netherlands and the USA. AB - There are many definitions of new ways of work, but working with a computer at another location than at the office or at the clients' location with Information Communication Technology as a support is becoming more prevalent. A new office having shared desks and facilitating informal meetings along with a changed leadership style is yet another way. Examining the experiences of alternative work styles, telework, between the Netherlands and the USA are especially apparent in the design of office environments as is the emergence of new leadership behaviors to promote safe and healthy work. PMID- 22317510 TI - 30 years of ergonomics at 3M: a case study. AB - The added value of the Ergonomics Program at 3M was found to be improved employee safety, compliance with regulations and reduction of work-related illness, increases in productivity, and quality and operating efficiency. This paper describes the thirty years of existence of this program. For the first twenty years, the program objectives were to: respond to requests for assistance related to work-related musculoskeletal disorder (WMSD) concerns, raise employee awareness of MSDs and ergonomics; educate engineers in ergonomics design; and develop ergonomics teams at manufacturing locations. Since the year 2000, 3M's Ergonomics Program has been in transition from a US-centric and corporate-based technical-expertled program to a global program applying participatory ergonomics strategies within a macroergonomics framework. During that transition, the existing program requirements were revised, new methods and program tools were created, and expectations for implementation at the manufacturing locations clarified. This paper focuses on the company's manufacturing ergonomics program activities during the past ten years and includes specifics of the program's objectives, risk assessment reduction process, and ergonomics technical expertise development. The main benefit achieved throughout the company is reducing employee injury while also increasing productivity and operating efficiency. PMID- 22317511 TI - Expectation changes and team characteristics in a participatory design process. AB - A human factors specialist researched the expectations of a culturally and professionally diverse team throughout a year long participatory design process of a large processing facility. For a deeper understanding of high-level team expectations and characteristics, the specialist collected data and information through in-situ ethnography and traditional case study methods, personal interviews, and a questionnaire that included a likert scale rating for expectation levels. Results found that expectation levels rated extremely satisfied for individual team members and the overall team itself before and during the participatory process. In contrast, expectations for upper management from the team were satisfied before the participatory process, but changed to uncertain, to unsatisfied, to extremely unsatisfied during the process. Additionally, the participatory design team exhibited high-level team characteristics to include honesty, competence, commitment, communication, creativity, and clear expectations. PMID- 22317512 TI - Participatory ergonomics and new work: reducing neck complaints in assembling. AB - A participatory ergonomics approach is used to create a new work environment, which is aimed at reducing neck complaints in a cell phone assembly. The participatory ergonomics program included an initiative, problem identification, a selection of solutions, an implementation and evaluation. Twenty-eight women, all operators on an assembly line of cell phone boards, voluntarily participated in the design and evaluation of a device before implementing the device to all 215 employees performing that job. Prior to and after the intervention, RULA, comfort experiences and interviews were used. After introducing an adjustable angled small counter, these measurements showed both posture and comfort improvements. 90% of the 215 workers preferred the new work station and the neck complaints were reduced in 75% of the group. It also showed that the initial prototype needed to be modified as to reduce its sharp edges/compression points for the forearm. This project shows the importance of iterative testing and that an initiative by workers enlarges the chance of successful implementation. PMID- 22317513 TI - Influences of mechanical exposure biographies on physical capabilities of workers from automotive industry - a study on possible dose-response relationships and consequences for short and long term job rotation. AB - This paper describes a field study in production areas of a vehicle manufacturing plant, where 106 male workers (aged from 20 to 63 years) were examined and interviewed by the authors. Aim of study was to identify relationships between specific physical worker capabilities and doses of mechanical exposures using self-developed standardized questionnaires as well as a battery of work-specific tests. The dependent variables are different "physical capabilities", classified using a five-point rating scale with regard to the grade of limitation of the respective capability. Independent variables are "age" and specific "mechanical exposures". Several exposures were combined and multiplied with their respective durations in order to determine doses on three different body regions - back, shoulder-neck and upper limbs. There are significant positive correlations between "age" and "dose of mechanical exposure on back/shoulder-neck/upper limbs region". The analysis of the relationship between dose of exposure and different capabilities to lift or reposition loads (with variable weight) shows weak significant correlations for all three body regions. Data analysis shows no significant correlations between any dose of mechanical exposure and capabilities to work in awkward body postures.These results should be considered in age management programs when scheduling future employee assignments to workplaces, especially for production systems where manual handling tasks are dominant. PMID- 22317514 TI - Impact of increasing productivity on work content and psychosocial work characteristics in Chaku-Chaku assembly lines - a follow-up study in a German automotive manufacturing company. AB - The current study aims at evaluating the reorganization of work processes on the basis of studies of three assembly lines in a well known component manufacture of the German automotive industry. It is of particular interest to evaluate the impact of the introduction of Chaku-Chaku assembly lines on the production goals, distribution of activities during one typical work day and psychosocial characteristics of the work environment. Findings indicate that the Chaku-Chaku assembly lines could represent a successful production strategy in order to enhance the output levels of work systems. However, the data show that interviewed assembly workers have spent more time on value added activities than before. The intensive perception of the time spent on main work activities (direct value added activities) and a simultaneous decrease of available discretionary time between work tasks seem to be related to the low level of the reported psychosocial work characteristics. PMID- 22317515 TI - Consolidated findings from 6 years research on the age-differentiated design of human-computer interaction. AB - The fast aging of many western and eastern societies and their increasing reliance on information technology create a compelling need to reconsider older users' interactions with computers. This paper summarizes the results of 6 years of research on the age-differentiated design of human-computer interaction. The well-known model of human information processing served as the theoretical framework. The model components ''sensory processing'', ''perception'', ''working memory'', ''decision and response selection'' and ''response execution'' were analyzed exemplarily in task settings on project management. In seven empirical studies with a total number of 405 participants between 20 and 77 years the human computer interaction was analyzed regarding effectiveness, efficiency and user satisfaction. For most but not all studies the results reveal that age-induced differences in human-computer interaction can best be compensated by an ergonomic ''design for all''. In some cases however an age-specific approach is favorable. PMID- 22317516 TI - Promoting work ability and well-being in hospital nursing: the interplay of age, job control, and successful ageing strategies. AB - Previous research shows that work ability of nurses decreases with age. In our study we therefore addressed the following questions: Do successful ageing strategies at work in terms of selection, optimization, and compensation (SOC) support the work ability of nurses? Does SOC mediate the relationship between job control (i.e., decision opportunities at work) and work ability? Does the mediation differ between age-groups? 438 nurses (Age Range 21-63 years) completed a questionnaire in the course of an employee survey. Results show that SOC is positively related with work ability. The positive effect of job control on work ability is significantly mediated by SOC. There are stronger mediating effects for elder nurses than for younger nurses. Results indicate that the interplay of job control and SOC at work helps to maintain the work ability of nurses in nursing care. PMID- 22317517 TI - What makes age diverse teams effective? Results from a six-year research program. AB - Based on a new model of productivity in age diverse tams, findings from a six year research program are reported in which data from more than 745 natural teams with 8,848 employees in three different fields (car production, administrative work, financial services) were collected. Moreover, central assumptions of this model were tested with a representative survey of the German workforce (N = 2,000). Results support both significant advantages and disadvantages for age mixed teams. Based on the findings, the following preconditions for the effectiveness of age diverse teams are identified: high task complexity, low salience and high appreciation of age diversity, a positive team climate, low age discrimination, ergonomic design of work places, and the use of age differentiated leadership. Based on these insights, we developed a new training for supervisors, which addresses the aforementioned aspects and seeks to improve team performance and health of team members. It was found that the training reduces age stereotypes, team conflicts and enhances innovation. Thus, we can conclude that effective interventions for a successful integration of elderly employees in work groups are available and that combinations of measures that address ergonomic design issues, team composition and leadership are to be strongly recommended for practice. PMID- 22317518 TI - Aging: physical difficulties and safety in cooking tasks. AB - It is known that many older people have difficulties in performing daily living activities such as cooking. These are due to the demands of the tasks and the changes in functional capabilities of the older people. This study examines cooking tasks performed by the aged that includes preparing and cooking meals, and storing kitchen tools in the kitchen. The objectives are to investigate the cooking difficulties encounter by older people and the safety concerning cooking tasks. This study focuses on individuals of age 65 years and above who can cook for themselves and/or family. Data were collected through observation, interviews, questionnaires and role play methods. The findings revealed that the common problems were due to the awkward body position where subjects had to bend down to take things from lower shelves, taking/storing things on higher shelves and cleaning the cooker. Moreover, the safety concerns were the layout of work centres (storage, cooker and sink), the use of cooker and opening packaging. It can be concluded that cooking difficulties are caused by inappropriate kitchen design and the decline of functional capabilities in older people. PMID- 22317519 TI - Field study of age-differentiated strain for assembly line workers in the automotive industry. AB - A field study in an automotive supply industry company was conducted to explore age-differentiated strain of assembly line workers. Subjective and objective data from 23 female workers aged between 27 and 57 years were collected at the workplace belt buckle assembly during morning shifts. Subjects with medication or chronic diseases affecting heart rate and breath rate were excluded. For subjective data generation different questionnaires were used. Before the Work Ability Index and the Munich Chronotype Questionnaire were completed by the subjects. Short questionnaires (strain-ratings, NASA-TLX) directly at begin and end of the work were used for obtaining shift-related data. During the whole shift (6 a.m. - 2.45 p.m.) bodily functions were logged with a wireless chest strap. In addition, the motion of the hand-arm-system was recorded for 30 times, 3 minutes each after a fixed time-schedule. First results show that younger subjects need significant less time for assembly (mean = 14.940 s) compared to older subjects (mean = 17.040 s; t(472.026) = -9.278 , p < 0.01). PMID- 22317520 TI - Symposium: Neuroergonomics, technology, and cognition. AB - This symposium describes collaborative research on neuroergonomics, technology, and cognition being conducted at George Mason University and the US Air Force Research Laboratory (AFRL) as part of the Center of Excellence in Neuroergonomics, Technology, and Cognition (CENTEC). Six presentations describe the latest developments in neuroergonomics research conducted by CENTEC scientists. The individual papers cover studies of: (1) adaptive learning systems; (2) neurobehavioral synchronicity during team performance; (3) genetics and individual differences in decision making; (4) vigilance and mindlessness; (5) interruptions and multi-tasking; and (6) development of a simulation capability that integrates measures across these domains and levels of analysis. PMID- 22317521 TI - The influence of flexible management practices on the sharing of experiential knowledge in the workplace: a case study of food service helpers. AB - Previous studies have shown that the job knowledge and prudent knowledge of experienced workers constitute a wealth that needs to be shared in workplaces to promote worker integration, job retention and occupational health and safety. It appears, however, that certain management practices undermine this knowledge sharing process. This case study of food service helpers in institutional food service departments is part of a research project aimed at comparing the impact of different work organization methods on knowledge sharing in the workplace on the basis of case studies carried out in several organizations. The results of this case study reveal that by destabilizing and weakening the work teams, flexible management practices create an environment that is not conducive to experiential knowledge sharing. PMID- 22317522 TI - Specialisation and training for fire-fighters driving heavy rescue vehicles: consequences for the development of operators? AB - This work was undertaken in France at the request of a local fire and rescue school in order to conduct an analysis of driving two types of heavy rescue vehicle with a view to improving training. This study took place in a context of specialisation: the drivers of these vehicles will henceforth only perform this type of task. Consequently, specific training has been designed in advance. Our study concerns the improvement of this training, taking account of the particularities of driving these vehicles in emergency situations typical to the profession of fire-fighters. The results stress first that driving of rescue vehicles in emergency situations is a multidimensional collective activity. Driving strategies identified share certain common objectives: "optimising trajectories", warn other road users, anticipate their behaviour and leave room for manoeuvre to counter and react to any unexpected behaviour. They include risks management for the potential victims of the incident and the risk of accidents during the journey. These initial results help identify certain recommendations for the training courses dealing with driving vehicles in emergency situations. They also provide a warning concerning the possible consequences of driver specialisation. PMID- 22317523 TI - Coordination meetings as a means of fostering collective learning among jury members involved in the validation of prior learning (VPL). AB - Jury members involved in the validation of prior learning (VPL) are supposed to draw parallels between the skills the candidate has acquired and the criteria established in relation to the frame of reference. The recalibration of criteria is a form of collective work. During meetings, jury members face common obstacles together. They try to sidestep the prescribed work and then collectively take ownership of it. Collective meetings allow responsibilities to be shared. This contrast between the imposition of extremely narrow prescribed work and the possibility of modifying prescribed work during collective meetings, sets a dialogic process in motion. Such a process gives jury members the opportunity to evolve in their practices. This ensures that jury members are always in a position to reflect on their own methods of action. PMID- 22317524 TI - Active participation in preventionist professional practices: a specific ergonomics training course. AB - Currently, the different forms of corporate management methods (quality circles, lean manufacturing, etc.) are usually based on employee mobilisation. Very often, the goal of this type of approach is at best, to ensure that employees embrace corporate projects, or otherwise to impose changes on them without taking into account the real work and difficulties that they face daily. However, do these employee solicitation methods converge with participatory approaches as envisaged by ergonomists and more generally, preventionists? Based on the observation that the activity of institutional preventionists evolves with regulatory constraints and work related to the monitoring of indicators, the implementation and steering of the participatory approach within companies may be a major lever for prevention. After describing the foundations of a participatory approach, this paper will present a training experiment aimed at implementing and promoting employee participation in prevention efforts. The content of this training is then analysed with regard to the balance between methodology and the use of trainees' narratives. The results of the training session are presented from the point of view of the development prospects for pedagogical tools and the organisation of the training. PMID- 22317525 TI - Landscaping: teamwork and integration into inter-individual coordination as a learning situation. AB - One of the dimensions of work that is not well known in training is teamwork and the work of the team leader. The team leader is the personne who provides local supervision. Teachers and trainers, as well as business employers aknowledge the place and importance of teamwork and the role of the team leader. However, most consider themselves, insufficiently prepared to offer training in line with these elements. This paper thus aims to present the results of an analysis of group work in the field of landscaping conducted from the perspective of team work and team leader learning and training. PMID- 22317526 TI - Being a trainer in the French vocational training system: a case study of job status and working conditions in relation to perceived health. AB - This communication presents part of an international project focused on the work of trainers from an ergonomics perspective. The objective is to identify in the French vocational training system the various types of job status of trainers and their impact on working conditions and health. In order to explore this issue, we met with 11 trainers, all volunteers, working in the music or human resources sectors. Semi-structured interviews and transcriptions of two weeks of the trainers' professional schedules form the data collected. The analyses show that trainers have various job statuses as trainers and sometimes hold down several jobs at the same time. These working situations create freedom but lack security. With very long daily or weekly working hours, the relationships with trainees and clients are qualified as both very interesting, but also one of the most difficult aspects of the work. The 11 trainers, who considered themselves to be in good health, do however declare infra-pathological disorders, which they often relate to their working conditions. These findings are discussed with regard to the literature and raise issues relating to ergonomic methods in activity analysis and situated action. PMID- 22317527 TI - Conditions, demands and constraints on trainers' activity: a case study in the Portuguese context. AB - The aim of the present study is to contribute to the analysis of employment and work conditions of Portuguese trainers, as well as to identify conditions, resources, demands and constraints of their work activities. Despite the lack of scientific knowledge on professional training, the topic has been playing a central role in modern societies. Several data collection strategies were used, namely the application of INSAT to 72 trainers, exploratory interviews with 10 trainers and collective interviews with 6 trainers. The analysis of the data collected highlights the changes in the selection of human resources in the sector as well as the contractual terms of the trainers, mainly independent workers. The intra and inter individual variability of working hours and the diversity of activities performed by each trainer also stands out. Finally, it is important to refer the spontaneous organization of trainers' work activities according to their training modality. PMID- 22317528 TI - "Obey", "disobey" or "tinker with" reforms to the system: a subject for French teacher trade unions to work on. AB - This paper presents our work to support and train members of the teaching sectors of two trade unions. The aim was to encourage participants to discuss practices, the difficulties in their day-to-day work and impediments to taking action, given the current reforms to primary education, and thereby assess the reforms' impact on the teachers' activity. It was also intended to help trade unions build up a collective dynamic around their work and re-positioning the work activity at the heart of their preoccupations. This project consisted of one/two day workshops held at local trade union branches. They were led by an ergonomist and a trade union representative. The discussions revealed that the prescriptions received from the management increasingly contradict the values of the profession. Therefore, in the name of professional ethics, different strategies of resistance have emerged, from minor modifications to the prescriptions received, to disobedience. However, adopting such strategies is itself a cause of suffering for teaching staff, and leads to some leaving the profession prematurely. We will discuss the difficulty trade unions have in dealing with the issue of work, their strategic positioning as regards developments within the profession, and the role an ergonomist can play in this process. PMID- 22317529 TI - Physical education and sport teachers' health: from expressed ill-being to hindrances of action. AB - The researches that specifically analyse the working conditions of teachers are few in the ergonomic literature. Our research relates more specifically to teachers of physical education and sports in french context of college. The research project described here includes both a quantitative exploratory survey (218 respondents) and qualitative case studies (interviews and observation), using the general framework of Activity Ergonomics. The results of this exploratory work tend to emphasize the importance of collective and organizational dimensions in the experience of teachers' physical education and sports. Specifically, in a perceived context of degradation of working conditions and accumulation of constraints, the collective and local ability to negotiate the various constraints on the activity appears to be a protective factor. This power to act, these margin of manoeuvre could be a relevant topic for future research. PMID- 22317530 TI - What is learned during the first moments of work? AB - The supervision of internships is often based on common sense. However, learning processes at workplace and their conditions remain partly unknown: what is really learned and under what conditions? Two studies on the learning of social working have been conducted, based on work analysis theories and methods. 6 experienced social workers and 4 interns in their first year of training have been interviewed according to the method of "explicitation" interview. The results show that professional learning can occur anyplace, anytime, under certain conditions and under certain forms that have been analyzed. These studies try to analyze the first internship as an entrance into a culture, through a psychological perspective. PMID- 22317531 TI - Prospective ergonomics: origin, goal, and prospects. AB - So far ergonomics has been concerned with two categories of activities: correction and design. We propose to add a third category: prospection, and by so doing, we introduce a new series of activities that opens up the future of ergonomics. Corrective ergonomics relates to the past and comes with a demand and a client. It is turned towards the correction of existing situations and aims to reduce or eliminate problems. Here, after delimiting and defining the problem, the challenge is to find the best solution. Ergonomics for design relates to the present and also comes with a demand and a client. It is turned towards the design of new artefacts that have already been identified by a client, and that will allow users to do some activity and attain their goals. Here, after defining the scope of the project and the functional requirements, the challenge is to do the best design. Finally, prospective ergonomics relates to the future and does not come with a demand and a client. It is turned towards the creation of future things that have not been identified yet. Here the challenge is to detect existing user needs or anticipate future ones, and imagine solutions. These three categories of activities overlap and are not exclusive of each other. In this paper we define prospective ergonomics and compare it with corrective ergonomics and ergonomics for design. We describe its origin, goal, and prospects, we analyze its impacts on education and practice, and we emphasize the need of new collaboration between ergonomics and other disciplines. PMID- 22317532 TI - Innovation and design approaches within prospective ergonomics. AB - In this conceptual article the topic of "Prospective Ergonomics" will be discussed within the context of innovation, design thinking and design processes & methods. Design thinking is essentially a human-centred innovation process that emphasises observation, collaboration, interpretation, visualisation of ideas, rapid concept prototyping and concurrent business analysis, which ultimately influences innovation and business strategy. The objective of this project is to develop a roadmap for innovation, involving consumers, designers and business people in an integrative process, which can be applied to product, service and business design. A theoretical structure comprising of Innovation perspectives (1), Worldviews supported by rationalist-historicist and empirical-idealistic dimensions (2) and Models of "design" reasoning (3) precedes the development and classification of existing methods as well as the introduction of new ones. PMID- 22317533 TI - Cognitive Chrono-Ethnography (CCE): a methodology for anticipating future user needs. AB - This paper proposes Cognitive Chrono-Ethnography (CCE), a new study methodology for understanding people's in situ behavior selections in daily life. People select their next behavior to maximize their satisfaction for a given behavioral needs. They appropriately coordinate available cognitive resources to make the best decisions by using their knowledge of past experiences and by processing input from the environment and individual intrinsic state. When a study field is specified, CCE starts by defining critical parameters for understanding people's behavior by considering the nature of behavior selection processes in the field in question, and then designing ethnographical field observations by taking into account the fact that their results will be described in terms of the specified critical parameters. The participants' behavior is recorded, followed by a series of structured retrospective interviews for the purpose of describing their present behavior and obtaining their history of behavioral development. Analysis of the interview results aid in developing models of present behavior selections and their chronological changes in the past. These models serve as defining future needs of persons who follow the same developing paths with a certain amount of delay, e.g., a few years of delay. This paper describes a CCE study of spectators of professional baseball games at a ballpark who have become frequent visitors to a baseball stadium in 5 years. PMID- 22317534 TI - Ethical issues raised by the new orientations in ergonomics and living labs. AB - User Experience Theory (UXT) provides us with criteria for designing products and technical systems for everyday activities (playing, learning, working,...) so as to satisfy users. Living Labs (LL), are plateforms used for the design and evaluation of technical systems. As such, they constitute tools that bring to this process some constraints., However these constraints have to be articulated to the UXT. In other words, UXT should specify the place, the role and function LL should play in the design of new products, how it should contribute to satisfying UX, and how the methods and techniques should be conceived or borrowed from other disciplines. UXT also raises ethical issues: impartiality (independent, public, replicable) of research models in the context of economical constraints (dependant, private, secret prototypes) and of industrial pressure, the use of intrusive and persuasive techniques, even with the prior informed consent of participants, ergo-marketing, deontology codes, the use of specific participants, belonging of an UX innovative solution, confidentiality with ICT, and so on. Because the UX, as well as LL literature, have shown little concerns for ethical considerations, till now, we define LL-UX ethical issues as a new research topic, and we list a number of problems to be solved in order to have an ethical LL-UX methodology for open innovation. PMID- 22317535 TI - Measuring a product's usefulness. AB - This paper explains how a product's usefulness may be defined and measured. Many aspects of consumer product assessments are conducted sub-consciously and this process is closely examined. A product's usefulness can be evaluated by measuring its advantages over alternative solutions based on specific criteria associated with fundamentals needs. When multiple criteria are involved, different weights are assigned to each. It should take into account the context in which the product is used. For the purpose of this paper, we use a formula to determine the relative usefulness of a variety of products in different contexts. We conclude that aspects of product's usefulness, connected with sub-conscious human decision making processes, can be a major factor in predicting acceptance and rejection rates. PMID- 22317536 TI - Anticipating needs and designing new items rapidly - a case study for the design of postural aid equipment. AB - In this case study, designers proactively proposed new product ideas to a client by using an ergonomic approach. This approach differs from a more traditional approach where one works within a specific, clientdefined project. The methodology used included basic ergonomic techniques such as task analysis and information gathering sessions conducted with users. It was adapted so that these enriched user sessions could be conducted within a short time period. After meeting with five users in seven days, designers identified 20 problems that could be tackled and eight design ideas that could be implemented over the short, medium and long term. The ideas encompassed a wide range of potential projects, including physical product improvements, new product lines, Web-site and software improvements and longer term research. Problems identified and ideas generated involved many disciplines including occupational therapy, mechanical engineering, graphical design, software engineering, sales and manufacturing know-how. This wide range was possible because designers were not constrained to specific project scopes and timelines. The client was involved in the idea evaluation process. As a result of this study two new projects were initiated so far. PMID- 22317537 TI - Drivers' safety needs, behavioural adaptations and acceptance of new driving support systems. AB - The aim of this paper is to discuss the contribution of two complementary approaches for designing and evaluating new driver support systems likely to improve the operation and safety of the road traffic system. The first approach is based on detailed analyses of traffic crashes so as to estimate drivers' needs for assistance and the situational constraints that safety functions should address to be efficient. The second approach is based on in depth-analyses of behavioral adaptations induced by the usage of new driver support systems in regular driving situations and on drivers' acceptance of the assistance provided by the systems. PMID- 22317538 TI - Activity analysis: contributions to the innovation of projects for aircrafts cabins. AB - This article presents results obtained from some ergonomics intervention in the project for the conception of aircraft's cabins. The study's aim is to analyze the contribution of the method adopted in the passengers' activities analysis in reference situations, real-use situations in aircraft's cabins, applied to analyze typical activities performed by people in their own environment. Within this perspective, the study shows two analyses which highlight the use of electronic device. The first analysis has been registered through a shooting filming in a real commercial flight. In the second one, the use is developed within the domestic environment. The same method has been applied in both contexts and it is based on activity analysis. Starting with the filming activity, postures and actions analysis, self-confrontation interviews, action course reconstruction and elaboration of postures envelopes. The results point out that the developed method might be applied to different contexts, evincing different ways of space occupation to meet human personal needs while performing an activity, which can help us with the anticipation of the users' needs, as well as indicate some innovation possibilities. PMID- 22317539 TI - Designing future products: what difficulties do designers encounter and how can their creative process be supported? AB - To remain competitive, companies must regularly offer new products to consumers. A major challenge for designers is therefore to come up with design solutions and define products that are both new and adapted to future users and usages. Although classic methods and ergonomic recommendations are useful in most run-of the-mill design contexts, they are of limited benefit when the design situation requires greater creativity. This paper therefore addresses issues related to product design by pursuing a triple objective: (1) highlight the difficulties encountered by designers in imagining and conceiving new products, (2) find out which conditions could help designers come up with creative ideas for innovative products, and (3) suggest methods and tools to support designers' creative process and help them take other stakeholders' needs and expectations into consideration. PMID- 22317540 TI - Health and safety strategy in Swedish agriculture. AB - In Sweden there is a joint focus on injury prevention in agriculture and this is coordinated through the Swedish Committee on Working Environment (LAMK). LAMK is a network working for a good, healthy and safe working environment in Swedish agriculture from the view of the enterprise with the humans in focus. It is a committee consisting of representatives of authorities, institutions, companies, research & education institutions and organisations referring to the green sector. Examples of on-going initiatives & partners are presented which are included in this mission against injuries in agriculture. It involves the Swedish Work Environment Authority,, the Federation of Swedish Farmers (LRF), the Swedish Institute of Agricultural and Environmental Engineering, Swedish University of Agricultural Sciences (SLU, the Federation of Swedish Forestry and Agricultural Employers (SLA) and the Swedish Municipal Worker's Union. PMID- 22317541 TI - The farrier's work environment. AB - The horse industry in Sweden has rapidly expanded in recent years. This increasing number of horses implies a greater need for more farriers. Shoeing a horse is hard physical work, and includes awkward work postures and repetitive movements. It is well known that hard physical work increases the risk of injuries and musculoskeletal problems. The risk is especially high for musculoskeletal disorders when certain movements are constantly repeated. Heavy or repeated unilateral loads lead to considerable stress on the muscles, which can lead to rupture and fatigue that can cause long term problems. A case study showed that farriers worked 75% of their work time with their backs in bent positions (often more than 70 degrees). Farriers are also exposed to risk factors in their physical environment like dust, noise and poor lighting. Risk of kicks and bites, eye injuries and burns are other factors that make their work environment hazardous. There are only a few studies available that have documented the farriers' working environment and these are not of recent date. A US study from 1984 described kicks and bites from horses, metal splinters in the eyes, heat exhaustion and problematic postures to be perceived as the greatest risks in their work. The back, knees and wrists were the most exposed body regions. There is a need for more current and in-depth studies investigating the farriers' working conditions in order to gain more knowledge of their health and work environment. The aim of the present study is to investigate the physical health and work environment of farriers. The investigation will use questionnaires, work load measurements and workplace analysis. The results will serve as a base for improvements concerning the design of the workplace, equipment, tools and aids as well as supplying recommendations about physical exercise and the correct work technique, etc. The results are planned to be incorporated in the education of farriers. PMID- 22317542 TI - What factors attract and motivate dairy farm employees in their daily work? AB - This study examined attraction and motivation factors important for people choosing to work and remain in the profession of dairy farm worker. The study comprised 194 agricultural students, 197 employed dairy farm workers and 147 employers. The study was based on questionnaires in which the key questions were: What would attract you to choose dairy farming as a profession? What attracts and motivates you in your daily work? What would motivate you to remain employed in dairy farming? Furthermore, in order to elucidate the farm employer's view, they were asked what they believed were important factors to attract and motivate young people to the profession. In general, the students, employees and employers had similar opinions on factors that attract and motivate dairy farm workers in their daily work. Although the order of priorities was different, they agreed that having fun at work, good leadership, feeling pride in their work, job security, good team spirit, living in the countryside, meaningful and interesting work, safe and healthy workplace, flexible work tasks, the farm having a good reputation and feedback from supervisors were among the most important attraction and motivation factors. PMID- 22317543 TI - Tractor accidents in Swedish traffic. AB - The objective of this study is to reach a better understanding of accidents on Swedish roads involving tractors and to suggest ways of preventing them. In an earlier study we analyzed police-reported fatal accidents and accidents that led to physical injuries from 1992 to 2005. During each year of this period, tractors were involved in 128 traffic accidents on average, an average of 7 people were killed, 44 sustained serious injuries, and 143 sustained slight injuries. The number of fatalities in these tractor accidents was about 1.3% of all deaths in traffic accidents in Sweden. Cars were most often involved in the tractor accidents (58%) and 15% were single vehicle accidents. The mean age of the tractor driver involved was 39.8 years and young drivers (15-24 years) were overrepresented (30%). We are now increasing the data collected with the years 2006-2010 in order to study the changes in the number of accidents. Special attention will be given to the younger drivers and to single vehicle accidents. Based on the results we aim to develop suggestions for reducing road accidents, e.g. including measures for making farm vehicles more visible and improvement of the training provided at driving schools. PMID- 22317544 TI - Occupational accidents among elderly farmers in Sweden. AB - The workforce in many countries nowadays is becoming older due to demographic change. Compared with many other occupations, farmers often work until a higher age. This study analysed occupational accidents to farmers in Sweden from an age perspective using data on 223 work injuries on farms and 990 road accidents involving tractors. The results showed that older farmers were not significantly more often injured than younger farmers, but appeared to suffer more hits and kicks from animals and were involved in more vehicle accidents than younger farmers. Older tractor drivers were more often involved in road turning accidents and in overtaking accidents involving private cars. Older farmers also sustained more skeletal injuries and took longer to heal after an accident. PMID- 22317545 TI - Social partners cooperation for reduction of musculoskeletal disorders in agriculture. AB - The European social partners in agriculture recognize the considerable frequency of musculoskeletal disorders (MSD) in the sector which has negative consequences for workers, employers, social security systems and hence for the whole society. They made an agreement in 2005 to tackle this problem and their main interest was finding good practices 'on the floor', with the involvement of the farmers and farming industries. A partnership with researchers from 4 different organisations across Europe, was created, taking into account both academic partners and/or partners experienced with the agricultural sector. GEOPA-COPA acted as a network partner with all the EU agriculture organisations. The project partners proposed a methodology how to collect the good practices. In total, 103 company visits were organised and 55 additional reports were collected. More than 140 good practices were defined going from easy, low-cost solutions to highly technological, more expensive solutions. All this information is disseminated via the project website (www.agri-ergonomics.eu) and summarised in 6 brochures. This paper focuses on the methodology to set up the ergonomic project with social partners. PMID- 22317546 TI - Relationship between productivity, quality and musculoskeletal disorder risk among deboning workers in a Chilean salmon industry. AB - The purpose of this ergonomic investigation is to establish a relationship between quality, productivity and risk of musculoskeletal disorder (MSD) in manual bone-removal process in the salmon fish industry. The method consists in a follow up study of 14 workers in a lane that processes salmon steak. Time between each steak (work cycle), quality of the steak's meat through inspection of deepness and length of the gapping generated by the manual bone-removal process and risk for musculoskeletal disorders through OCRA method were considered for this study. IMC and musculoskeletal Nordic Questionnaire of Kourinka were applied to the workers evaluated. Fourteen women worker's completed the evaluation, age 37.67 +/- 8.1, with 65.27 +/- 34.41 months of experience, with an IMC of 27.18 +/ 3.87 (1.52 +/- 0.057 meters of height) at the time of the evaluation. Time for deboning per steak averaged 38 +/- 14 seconds with 68.33 +/- 14.79 steaks per hour per worker. In quality terms, 74% of the steaks were qualified as "premium steaks" and 26% as "grade or industrial" (lower category and cheapest price). OCRA index for the right hand average 13.79 +/- 4.59 and 3.59 +/- 0.41 for the left hand. From Nordic questionnaire 80% of the workers manifested musculoskeletal symptoms in the right hand/wrist, followed up by shoulder with 60% of the workers and arm/elbow with over 50%. There was no statistically significant relationship between productivity and quality of the steak after manual bone removal process and between quality and MSD risk. However, there was a statistically significant relationship between productivity and MSD risk (p<0.05). Discussion around the results allows to see complementary results that did have strong correlation between MSD risk and the presence of lower grade salmon steaks and between areas that present musculoskeletal symptoms (MSS) and the intensity of the MSS (p<0.05). The results showed that further research is needed to validate these relationships, due to the increasing demands of health care services from this productive sector, considering its importance for this region. PMID- 22317547 TI - Ergonomics and design in the Brazilian agricultural sector: a proposal to build matrix of contradictions. AB - The paper presents a correlation between the parameters of classical TRIZ and variables of analysis of the EWA to construct a matrix of contradictions in ergonomics, with the objective of assisting the designing processes in the Brazilian agricultural sector. Given the representativeness of the sector in the economy, the boundary conditions in which the activities are developed and their impact on the health of workers, this proposal should contribute to the development of adaptable solutions and the promotion of Decent Work. PMID- 22317548 TI - Ergonomic analysis in the bagging of gran equipment: unsuitability of the work stations. AB - This analysis was performed in the industry for bagging grain (granular urea) nitrogen fertilizer factory in order to raise the causes of accidents on the operators. Data collection through direct observation and interviews done with the managers and operators have identified the causes of accidents. The results show an evident fact: the working conditions of bagging grain cause embarrassment to the employee, as well as the emergence of pathophysiology due to overload, then the problems of work organization involving mainly equipment, tools and accessories inadequate. At the end of this work are related suggestions, which has as its goal the reduction or even elimination of accidents involving operators bagging grain. PMID- 22317549 TI - Workload composition of the organic horticulture. AB - This project aimed the characterization of the physical workload of the organic horticulture by determining the frequency of exposure of operators to some activity categories. To do this, an adaptation of the PATH method (Posture, Activities, Tools and Handling) was done to be used in the context of agriculture work. The approach included an evaluation of physical effort demanded to perform the tasks in the work systems from an systematic sampling of work situations from a synchronized monitoring of the heart rate; a characterization of posture repertoire adopted by workers by adapting the OWAS method; an identification of pain body areas using the Corlett diagram; and a subjective evaluation of perceived effort using the RPE Borg scale. The results of the individual assessments were cross correlated and explained from an observation of the work activity. Postural demands were more significant than cardiovascular demands for the studied tasks, and correlated positively with the expressions of bodily discomfort. It is expected that, besides the knowledge obtained of the physical effort demanded by organic horticulture, this project will be useful for the development of new technologies directed to minimize the difficulties of the human work and to raise the work productivity. PMID- 22317550 TI - Assessment of psychosocial risk factors. AB - Aspects of work may not only contribute to physical stress but psychological stress as well. As long as we believe we have adequate control over all aspects of our job, we may experience normal stress. However, if we believe we have little control over job demands, we may suffer from distress with accompanying ill health and possible irrational behaviours. Under distress, the probability of an accident increases greatly. Research is examining work factors such as performance monitoring, incentive pay systems, and unreasonable management production demands to determine whether these factors have a negative effect on the musculoskeletal system. Another related area of research is to determine which personal, work, or societal factors contribute to acute musculoskeletal disorders developing into chronic or disabling problems. OBJECTIVES: This symposium will discuss methods of identification of psychosocial risk factors among the workers engaged in video display terminal use which is practised at our tertiary level rehabilitation centre. PMID- 22317551 TI - Physical examination, special tests and investigations for the diagnosis of WRMSD. AB - Physical examination will enable the clinician to link the information obtained from history and physical findings to make the precise diagnosis, patient education, to design an effective treatment plan and optimum rehabilitation prescription. PMID- 22317552 TI - Ergonomic workplace analysis (EWA). AB - Work Related Musculoskeletal disorders (WRMSDs) create a significant financial burden to both employer and employee that includes the cost of treatment and lost work time. There is a growing demand to implement early identification and effective prevention strategies, aimed at early intervention in employees prior to possible absenteeism due to foreseen sickness or disability. A wide range of conditions may be considered as MSDs, including myofascial pain syndrome, fibromyalgia, peripheral entrapment neuropathies (carpal or cubital tunnel syndrome), tenosynovitis, epicondylitis, and others. Several multidisciplinary rehabilitation centres such as RECOUP have developed a comprehensive, systematic and thorough medical examination protocol for WRMSD patients. The aim is to obtain anatomically precise clinical findings as a guide to therapy. These assessment protocols typically includes Questionnaire data, Physical examination protocol, Special Examination tests and Laboratory tests. A methodical medical evaluation protocol produces a patient-specific list of symptoms and coordinated physical findings. Such protocols provide a sounder basis for developing a biomechanical and ergonomic explanation for the WRMSD patient's injuries and for planning and monitoring therapy. Importantly for the WRMSD patient, it also provides a detailed explanation of symptoms that are experienced and a logical plan for alleviating them. MWRSD patients should not be dismissed as having vague or non physiologic complaints without this type of evaluation. OBJECTIVES: This paper will discuss methods of identification of ergonomic risk factors among the workers engaged in video display terminal use which is practised at our tertiary level rehabilitation centre. PMID- 22317553 TI - History taking. AB - History taking is the staple essential backbone for making an accurate diagnosis; it will enable the clinician to make a provisional diagnosis in most of the cases. The following rules should be taken in to consideration for while taking history. OBJECTIVES: The history taking will enable the clinician to organise the patient's story, filter the information which links to common musculoskeletal disorders by means of clinical reasoning, to fully understand the patient's present health status and to form a provisional diagnosis. PMID- 22317554 TI - The passing of the shift in aircraft maintenance - a task that produces deaths. AB - Maintenance tasks, especially in heavy maintenance, may not be completed in a single shift. Aircraft maintenance technicians often take work in progress by colleagues, and spend the incomplete work for a change of team. The need for accuracy and efficiency of information transfer in many cases, without having time to have a meeting to pass the service is a crucial aspect of maintenance work. The ideal shift change can occur normally before delivery and continues to proceed normally after delivery. Although a shift change create challenges for communication, they also offer opportunities to detect and correct errors, where the task of delivery is an opportunity to identify the problem and fix it. In this case, the task was done correctly the first round, however, a problem began when the second round took. One example is a case in which the first round have removed a defective part for replacement and let the component of aircraft at end of turn with problems. Instead of ordering and installation of an operational component, the second round was then reinstall the faulty component, not realizing he had information about the problem attached. PMID- 22317555 TI - Influences of tactile-dot height and tip radius of curvature on the operational performance of cellular phones. AB - Tactile dots located on operation keys of consumer products such as cellular phones contribute to improving accessibility for older people and people with visual impairment. The Japanese Standards Association (2000) and the International Organization for Standardization (2011) standardized tactile dots. However, reliable data on the appropriate sizes and the shapes was not necessarily available. The purpose of this study is to evaluate influences of the height (0.1, 0.3, 0.55, and 0.75 mm) and the tip radius of curvature (0.1, 0.3, 0.5, 0.7, and 0.9 mm) of tactile dots on the operational performance of cellular phones in younger and older people. Sighted younger and older participants, whose hand was covered by a curtain, operated cellular phones with a tactile dot on its key 5 and without a tactile dot. As the result, both participants performed better at a particular height with larger tip radius of curvature. Furthermore, older participants operated better at high dots like 0.55-0.75 mm. In contrast, younger participants performed better at 0.3 mm and relatively poorly at 0.1 mm and 0.75 mm. Thus, comparatively high tactile dots are useful for improving the accessibility of products for the older and there is an appropriate height range for the younger. PMID- 22317556 TI - Influences of the edge radius of curvature of tactile dots and bars on their discriminability. AB - Tactile dots and bars serve as tactile landmarks so that people with visual impairment can use same consumer products as those used by sighted people. However, reliable age-related data on the appropriate sizes and the shapes was not necessarily available. The purpose of this study is to evaluate influences of edge radius of curvature of tactile dots and bars on their discriminability in younger and older people to determine the appropriate size of tactile bars (as distinguished from tactile dots). Sighted younger and older participants tactually discriminated the tactile dots and bars presented individually, in random order, by a two-alternative forced-choice task. The results showed that both participants discriminated tactile bars from tactile dots faster and more accurately as the dimensional difference between bar length and width increased, regardless of conditions of edge radius of curvature. Therefore, longer dimensional difference between width and length of tactile bars is an important factor to discriminate tactile bars correctly. On the other hand, tactile dots with a larger edge radius of curvature have higher discriminability than tactile dots with a smaller edge radius of curvature in the case of dots of identical height. PMID- 22317557 TI - A literature review of major perceptual, cognitive, and/or physical test batteries for older drivers. AB - Driving is one of the most complex tasks that humans perform on a regular basis, placing significant demands on human perceptual, cognitive, and motor capabilities, so age-related declines in these capabilities negatively affect driving performance. Although older adults create a risk on the road because of their high crash rates, it is important to note that not all older drivers have impaired driving performance or high crash risk. Thus researchers have developed test batteries to identify at-risk older drivers. The literature pertaining to the development and testing of at-risk driver assessment tools, including major assessment tools and evidence supporting their use is reviewed. PMID- 22317558 TI - Examining the impact of age and multitasking on motorcycle conspicuity. AB - This poster presents a study to assess one's ability to detect motorcycles under different conditions of conspicuity while performing a secondary visual load task. Previous research in which participants were required to detect motorcycles revealed differences in age (young adults/older adult) as well as differences associated with motorcycle conspicuity conditions. Past research has specifically found motorcycles with headlights ON and modulating headlights (flashing) to be more conspicuous than motorcycles with headlights OFF within traffic conditions. The present study seeks to provide more information on the effects of multitasking on motorcycle conspicuity and safety. The current study seeks to determine the degree to which multitasking limits the conspicuity of a motorcycle within traffic. We expect our results will indicate main effects for distraction task, age, gender, motorcycle lighting conditions, and vehicular DRLs on one's ability to effectively detect a motorcycle. The results have implications for motorcycle safety in general and through this research, a better understanding of motorcycle conspicuity can be established so as to minimize the risk involved with motorcycle operation. PMID- 22317559 TI - Movement-in-depth, cognitive impairment, and crash risk. AB - In this study, 243 cognitively intact and cognitively impaired older participants' movement-in-depth (looming) abilities were assessed using a portable device that we had previously developed in our laboratory. Results indicated normative relationships between looming ability and age, looming ability and driving violation records, and age and driving violation records. Findings also confirmed the validity and reliability of the measurements taken with the device. In conclusion, this device may be useful for identifying drivers at risk for rear-end collisions, developing effective training interventions, and creating fair and valid driver licensing tests. PMID- 22317560 TI - Study of postures in sugarcane cutters in the Pontal of Paranapanema-SP, Brazil. AB - The expansion of sugarcane monoculture in Brazil in the last decades has pointed out to the necessity of considering the question of sugarcane cutters occupational health. In this work we present a cross-sectional study aiming to examine the occupational posture of a group of sugarcane cutters, which work in a cane field located in the region of Pontal do Paranapanema- SP, Brazil. The study was made using the Ergonomic Analysis of Work - EAW methodology and the postural analysis method by Win-OWAS. Through the obtained records of postures, it was observed that during a workday the sugarcane cutters remain standing erect on two legs or in one leg 66% of the time and that their trunk remain tilted and in rotation, according to 63% of the positions categorized. It was also observed that the sugarcane cutter trunk performs repetitive and boundless movements during his routine of work, which can expose this individual to additional wear of their musculoskeletal functions. The activities in which the individual engages have favorable or adverse influence on his posture. The repetitive movements involved in specialized occupations are equivalent to repeated exercises, thus may be responsible for the excessive development of certain muscle groups. The study suggests that the postures adopted by sugarcane cutters can overload their musculoskeletal system and predispose the cutters to work related musculoskeletal diseases. PMID- 22317561 TI - Postural analysis of workers in a typical meat processing company in Brazil. AB - Companies have increasingly sought strategies that will ensure a more competitive position in the marketplace. Among these strategies adopted by companies include the health and welfare of the worker, factors currently valued by consumers, especially those of most demanding market. Thus, the postural analysis is of great importance and interest because it is the study of positioning related to body parts like head, torso and limbs, capable of producing loads that may be excessive or insufficient causing disturbances in the muscle skeletal system worker. The aim of this study was to perform a postural analysis of the main sectors of workers (slaughter, cutting room, special cuts, packaging and dispatch) of a typical refrigerator pig industry in Brazil during the execution of their daily activities as well as developing proposals to minimize and/or eliminate the diseases and accidents. The study followed the safety norms of Brazilian Ministry of Labor and Employment. The posture analysis used the OWAS (Ovako Working Posture Analyzing System) methodology. The postures assumed by workers in the sector of packaging were as the most in need of emergency and quick action. PMID- 22317562 TI - The ergonomics analysis of work: a case study in a experimental farm. AB - This work presents the initial steps of ergonomic analysis of industrial activities, which are being held in the premises of an Agricultural Experimental farm belonging to an institution of higher education. The methods employed in the initial step was confined to desk research, its purpose was to know the demographic profile and understand organizational structure followed by systematic observations in workplaces using semi-structured interviews and a questionnaire of perception to operators. The presentation of the results will provide a summary of the analysis of activity sectors visited, understanding the biomechanical efforts entered (posture and strength), as well as the evaluation according to the perception of officials to respect the constraints, ambience and suggestions. It was noted that 90% of employees surveyed feel some kind of discomfort. It also highlights the age factor of this questionnaire, in which the majority (90%) is above 40 years old, and this fact confirms and reinforces the appearance or accumulation of injuries among the employers. At this stage there was no intention to deploy improvements, but create assumptions and guide future intervention actions that can be performed. PMID- 22317563 TI - Pesticide exposure and sprayer design: ergonomics evaluation to reduce pesticide exposure. AB - Plant protection products are used in agriculture to improve yields, but this use can cause contamination of the environment and is also likely to have adverse short and long term effects on agricultural workers. This poster describes a systems approach to reducing the risk of operator exposure to plant protection products through the introduction of ergonomics to the design process of large agricultural sprayers. PMID- 22317564 TI - On the road toward the development of clothing size standards and safety devices for Chilean workers. AB - The range of sizes used in Chile for clothing comes from criteria developed in continental Europe, mainly the EN 13402 standard. Any standard adopted by a country should consider the anthropometric dimensions of the user population, particularly to discern the ratio of garments for different size. Consequently, the purpose of this study was to propose standards for the size of clothing based on anthropometric characteristics of a sample of Chilean miners. The study was conducted in 447 male workers. The age and body weight were measured in each workers as well as their percentage of body fat. Anthropometric measurements for garments were made according to the criteria of the European Community (EN 13402 1) and ISO (8559- 1989). Body dimensions for the design of gloves, shoes, helmets and caps, clothes that cover the upper part of the body and clothes that cover the lower part were measured. The results obtained made it possible to establish the percentage of workers falling within the range of sizes that manufacturers consider as reference. One of the main conclusions of the study is the need to carefully consider a set of complementary anthropometric measures, which can help to improve the comfort of costumes, to the extent that the providers adapt their designs to the characteristics of Chilean workers. PMID- 22317565 TI - Metrology and ergonomic mensuration parameters. AB - This poster intends to show how measurement, its concepts and methods are decisive to the ergonomic praxis and why their agents should be aware of how incertainty can be taken in the process in order to increase the accuracy of measurement and findings. PMID- 22317566 TI - A study of automotive workers anthropometric physical characteristics from Mexico Northwest. AB - Due to the lack of anthropometric information in northwest Mexico, we did an anthropometric study that represents the population physical characteristics and that is reliable for the design or redesign of workstations. The study was divided in two phases. The first one was the anthropometric study of 2900 automotive industry workers in northwest of Mexico. The study includes 40 body dimensions of 2345 males and 555 females personalized to be used in future researches. Second phase includes compared anthropometric characteristics of population reported in four Mexican studies and a Colombian study against the current study. Benefits of this project are: a reliable database of anthropometric characteristic of automotive industry population for workstations design or redesign that match with the users, increase product quality and reduce economic, medical and union complains. PMID- 22317567 TI - Anthropometric data of adult wheelchair users for Mexican population. AB - The aim of the study was to obtain anthropometric data of adult wheelchair users at Mexico. This study count with 108 disabled people (56 men and 52 women) using the wheelchair and having the upper extremities sufficiently efficient to perform professional activities. The subjects were aged 18-60. From the measurements obtained, it can be said that in each of these measures was observed that men have larger dimensions than women, except for body depth, in which women had a slightly greater difference. When comparing the data in this study against other studies it shows that there is a significant difference between the averages of these studies. Similar results were obtained when comparing our data against data of standard population. Anthropometric data obtained through this study appear to be the only of this kind in Mexico and showed significant differences between measures of disabled persons and standard persons. the use of these data may be helpful for the proper design of workstations designed for use by adults who use. PMID- 22317568 TI - Analysis of the suitability of furniture university - anthropometric characteristics of user. AB - This study objective show if the furniture university are according anthropometric characteristics of user. PMID- 22317569 TI - A practical approach to the assesment of manual handling equipment for cargo: multinational abrasives in Brazil. AB - The Manual Handling of Loads is an activity present in virtually all production system, when developed without ergonomic principles of design and sizing can generate several instances of discomfort and musculoskeletal disorders. This work was carried out to measure, set limits and risks and guide specifications for the cargo handling carts in a specific company, tracing the anthropometric profile of the productive population and performing a quantitative evaluation of forces and design models of cars used in the company. PMID- 22317570 TI - Anthropometry of Algerian elderly. AB - In Algeria, a lot of attention is given to the elderly by both the government and private institutions. On the government side, two ministries participate in caring for the elderly. These are the ministry of social development and the Ministry of public health. On the private side, a lot of effort is given to the elderly through many societies and centres. If the elderly is to live independently and self-efficiently, whether at home or in social care institutions, equipment, tools, environment, daily-use items, and personal-use items should be designed for them, so that their needs are entirely satisfied, and abilities and limitations are carefully considered. Therefore, this study was carried out to provide anthropometric data of the elderly in Algeria, so that it may be used either to design equipment for them or to evaluate it in order that its use is efficient, and safe. Therefore, An anthropometric study of Algerian elderly was carried out. 29 body dimensions were measured. Mean, variation measures, and percentiles, were calculated. Body dimensions results were presented in one table so that they can easily be used by designers. PMID- 22317571 TI - A study on the influence of headphones in auditory perceptual function. AB - The focus of this study is a human's ability to make full use of listening and hearing. This ability consists of dividing auditory information into a signal and a noise. To evaluate the risk of using headphones, the study investigated the auditory perception when a warning sound is given in the presence of environmental noise. PMID- 22317572 TI - Effects of placement point of background music on shopping website. AB - Consumer on-line behaviors are more important than ever due to highly growth of on-line shopping. The purposes of this study were to design placement methods of background music for shopping website and examine the effect on browsers' emotional and cognitive response. Three placement points of background music during the browsing, i.e. 2 min., 4 min., and 6 min. from the start of browsing were considered for entry points. Both browsing without music (no music) and browsing with constant music volume (full music) were treated as control groups. Participants' emotional state, approach-avoidance behavior intention, and action to adjust music volume were collected. Results showed that participants had a higher level of pleasure, arousal and approach behavior intention for the three placement points than for no music and full music. Most of the participants for full music (5/6) adjusted the background music. Only 16.7% (3/18) participants for other levels turn off the background music. The results indicate that playing background music after the start of browsing is benefit for on-line shopping atmosphere. It is inappropriate to place background music at the start of browsing shopping website. The marketer must manipulated placement methods of background music for a web store carefully. PMID- 22317573 TI - Critical analysis about solutions and models of solar shades in non-residential buildings from tropical regions. AB - Whereas the non-residential buildings consume a significant percentage of the total energy produced by the city, is important that these buildings have for such consumption is reduced or consumed in a conscious way. To do so, using concepts of energy efficiency, this work is to explain passive strategies with the use of flexible solar shades that help to get a favorable outcome with respect to the performance of the building right in the initial stages of planning and design. Once initial gains can be obtained and the architecture constants that value at the same time provide better working conditions and indoor comfort. PMID- 22317574 TI - Mass of materials: the impact of designers on construction ergonomics. AB - Many construction injuries are musculoskeletal related in the form of sprains and strains arising from the handling of materials, which are specified by designers. The paper presents the results of a study conducted among delegates attending two 'designing for H&S' (DfH&S) seminars using a questionnaire. The salient findings include: the level of knowledge relative to the mass and density of materials is limited; designers generally do not consider the mass and density of materials when designing structures and elements and specifying materials; to a degree designers appreciate that the mass and density of materials impact on construction ergonomics; designers rate their knowledge of the mass and density of materials as limited, and designers appreciate the potential of the consideration of the mass and density of materials to contribute to an improvement in construction ergonomics. Conclusions include: designers lack the requisite knowledge relative to the mass and density of materials; designers are thus precluded from conducting optimum design hazard identification and risk assessments, and tertiary built environment designer education does not enlighten designers relative to construction ergonomics. Recommendations include: tertiary built environment designer education should construction ergonomics; professional associations should raise the level of awareness relative to construction ergonomics, and design practices should include a category 'mass and density of materials' in their practice libraries. PMID- 22317575 TI - Abandonment and accessibility in railway historical buildings: Central do Brasil and Leopoldina Railstation. AB - This paper aims to demonstrate the evolution of a study in the city of Juiz de Fora-MG, whose objective is the assessment of areas of train station in relation to the inclusion of people with disabilities and consequently promote the historical and cultural heritage of this city. The railway buildings are important landmarks in the history of the city and its surroundings was formed the first core of urban development. Because this building was of the early nineteenth century, these were not designed to assist people with disabilities, in effect, we observed that the buildings are being underutilized. The difficulty of insertion of incentive policies is therefore not due to the commitment by the majority, making the deployment of new access. PMID- 22317576 TI - The question of the ergonomic use of virtual models. AB - The comfort and functionality between man and his surroundings are the main goals of ergonomics, making it are increasingly in the production process. Many companies have tried Virtual Reality Center (VRC) to assist the analysis and development of ergonomic products. The use of virtual models brings many benefits to the design of products, including greater flexibility, speed and quality, and facilitates the control and reporting, also integrating all stages of the project. There are still some difficulties for the deployment of these resources, like the need for more powerful computers and specialized professionals. Possibly, the VR will be indispensable to the construction in some years, becoming a tool of fundamental importance to the professionals. PMID- 22317577 TI - Differences in cashiers work technique regarding wrist movements when scanning groceries. AB - Checkout cashier work can be repetitive and hand-intensive. Differences in workstyle might explain why some cashiers develop symptoms and other do not. Work technique is one part of the workstyle concept. The aim of this study was to analyze if there were differences in work technique among cashiers in to what extent they use large or small wrist movements when scanning groceries. Wrist movements of 17 cashiers were video recorded. The results revealed large variation among the cashiers in if they use large or small wrist movements when handling the groceries. This indicated there is a potential for some cashiers to improve their work technique. PMID- 22317578 TI - Ergonomics analyses of five joineries located in Florianopolis-SC, using the LEST Method. AB - Considering the goal of Ergonomic Work Analysis to establish, from the point of view of workers, safe, healthy, comfortable and efficient environments, this study propose to analyze the work situation of machine operators at five joineries from Florianopolis-SC. For this, it was applied the LEST Method to evaluate the task made by the operators, considering the physical, cognitive and organizational work environment. As results, it was identified the main ergonomics problems of these workstations, presenting an ergonomic diagnosis and their implications on health and safety of workers. As result, it was concluded that the main ergonomics problems at joineries are related with noise, with constant load of weight and with the postures taken. Besides these problems, others were diagnosed, for example, the pressure for workers to comply strictly the task stipulated and also the poor training and capacity of workers. PMID- 22317579 TI - Experimental indicators of ergonomic wellness and quality of life: salivary and hair cortisol. PMID- 22317580 TI - Increased of Brazilian productivity in the slaughterhouse sector: a review. AB - Due to Brazil is a tropical country has activities in occupational exposure to cold restricted to few sectors especially the meatpacking industry. Taking into account that the country in 2010, was again the largest exporter of poultry meat in the world and consequently employing a large number of workers for their slaughter and processing. The search for greater productivity can result in an increase in work rate, as indicated in this sector as monotonous, repetitive and uncomfortable. According the Programa de Frigorifico it was found that within six years, about 20% of the six thousand workers in a slaughterhouse in southern Brazil, received welfare benefits due to musculoskeletal diseases. Adding to this, the lack of parameters for the Brazilian standardization concerning occupational activities carried out in cold. Although several epidemiological studies point to the cold as a risk factor for occurrence or aggravation of musculoskeletal disorders, research in this field is still limited and often contradictory conclusions. This article aims to review developments concerning the poultry industry and the fridge in Brazil, as well as raising the question about the increased productivity of the slaughterhouse, since it has already shown a high prevalence of musculoskeletal disorders related to work. PMID- 22317581 TI - The ergonomic process of an automotive company in Brazil: a study case. AB - The goal of this paper is to present the ergonomic process of an automotive company, whose focus is on the adaptation of the work conditions to the psychophysiological characteristics of its employees. The planning and the development of the ergonomic actions took place in three distinctive stages: ergonomic analysis of the work post (stage 1), ergonomic adaptations (stage 2) and Ergonomic Committee (stage 3). The activities started in June 2006 and have lasted to the current date, keeping a permanent improving process. The procedure adopted was based on the ergonomic analysis methodology proposed by Wisner (1994:1997) and the stages of the Ergonomic Analysis of Work presented in the 17 NR Regulatory Manual (MET, 2002). The paper's approach focused on the voluntary participation of workers from different areas and different hierarchical levels of the organization throughout all the stages of the process. The methodological procedures included descriptive research techniques, exploratory and qualitative research criteria, background and guidelines available in literature and legislation, as well as company information. Among the main results it can be mentioned the satisfaction of the employees regarding the appropriate work conditions, cultural and organizational changes and the creation of an Ergonomic Committee in the company. PMID- 22317582 TI - Ergonomic risks in mining companies: a study in Paraiba/Brazil. AB - The growing concern for the welfare of workers in the work environment, the importance of widespread use of ergonomics in the different sectors of industry. Yet most corporate practices that work with rudimentary or great need for human handling of materials is not fully in line with the ergonomic aspects. Given this, this article aims to identify ergonomic hazards in mining to later propose improvements in the process. After a series conducted plant visits, found that workers are exposed to various ergonomic risks, which entails the need for new healthy practices in the workplace. Finally, a series of proposals are submitted in order to avoid possible occupational diseases. PMID- 22317583 TI - The challenges of interdisciplinary education and its application on teaching ergonomics. AB - The education in Brazil is still strongly based on traditional teaching methods that reinforce a passive attitude of the student. Despite the educational guidelines indicate the need for more liberating and interdisciplinary methodologies, there are few actions for change. Within this context, interdisciplinary appears as an important tool to help the creation of a new thinking in education, proposing the connection between the parts of an area of knowledge. In this way leading the student to develop a more critical and reflective thinking about the reality of the community where he lives. Being understood ergonomics as a scientific discipline that looks for the interactions among humans and other elements of a system in order to optimize human well-being and overall system performance, interdisciplinary has become essential in this process. The aim of this study was to discuss the educational foundations of interdisciplinarity and their applicability in the teaching of ergonomics in the context of Brazil. PMID- 22317584 TI - Job satisfaction among control room operators of electrical systems. AB - Shift workers from control centers of electrical systems are a group that has received little attention in Brazil. This study aimed to compare workers' job satisfaction at five control centers of a Brazilian company electrical system, and according to their job titles. METHOD: The Organization Satisfaction Index (OSI) questionnaire to assess job satisfaction was used. ANOVA was used to compare OSI means, according to job title and control center. The results showed that there is no difference in job satisfaction among job titles, but a significant difference was found according to the control center. A single organizational culture cannot be applied to several branches. It is required to implement actions that would result in job satisfaction improvements among workers of all studied control rooms centers. The high level of education of operators working in all centers might have contributed to the similar values of perceived satisfaction among distinct job titles. PMID- 22317585 TI - Analysis of the ergonomic usage of the ARMflex in the odontological area. AB - The aim of this paper is to analyze the importance and applicability of ARMflex in the odontological area and its influence in preventing or stopping the involuntary habit of improperly positioning the hand under the face or under the pillow. The ergonomic usage of ARMflex influences the design in odontological areas and innovates in the semi-immobilization of the patient to prevent future orthodontic problems. PMID- 22317586 TI - The struturing of an Ergonomics Program as a Center of Occupational Health Component in a public health institution. AB - This article presents the description and discussion of a pilot project in an ergonomic action developed in a public health institution. This project involves the implantation of an Ergonomics Program (PROERGO) in a department of this institution, guided by a methodology structured on six stages, referenced in the literature by ergonomics authors. The methodology includes the training of workers and the formation of facilitators and multipliers of the ergonomics actions, aiming to the implementation of a cyclical process of actions and the consolidation of an ergonomics culture in the organization. Starting from the results of this experiment we intend to replicate this program model in other departments of the institution and to propose the methodology applied as a strategy of intervention to Occupational Health area. PMID- 22317587 TI - Analysis of working conditions focusing on biological risk: firefighters in Campo Grande, MS, Brazil. AB - Firefighters are exposed to a wide range of risks, among them, biological risk. The objective was to analyze working conditions of firefighters in the city of Campo Grande, MS, Brazil, focusing on risk conditions of exposure to biological material. Three hundred and seven (307) firefighters were interviewed for data collection and observed for ergonomic job analysis (AET). RESULTS: 63.5% of the firefighters suffered some kind of job related accident with blood or body fluids. Statistically significant association was found between having suffered accidents at work and incomplete use of personal protective equipment (PPE). About AET regarding the biological risks, 57.1% of all patients had blood or secretions, which corresponds in average to 16.0% of the total work time, based on a working day of 24 h. Besides biological risks, other stressing factors were identified: emergency and complexity of decision, high responsibility regarding patients and environment, and conflicts. Health promotion and accident prevention actions must be emphasized as measures to minimize these risks. PMID- 22317588 TI - Ergonomic analysis of the work conditions of porters and owners of the Supply Center of Campinas, SP. AB - Transforming work conditions is part of the ergonomic action that should help to improve work situations that brings risks to the workers health. six workers were observed in different locations of the supply center (Central Free Market, Free Market 2, Flowers Market and Permanent Shed 4). During the observation of workers to the Ergonomic Analysis of Work - AET (Rohmert and Landau) was performed. The workers were divided into two groups: porters and owners. The porters were the most susceptible to the risks of work and minor accidents with sharp wood from boxes or even risk of traffic accidents as pedestrians. However, regarding the use of mental ability for negotiations, use of computers and organizing and planning the establishment of work, the owners were the ones that most time played these activities. The ergonomics advocates work that can be transformed and that favors employee and employer. It is, therefore, intended to redefine the strategies that are embedded into the organizational structure of work. PMID- 22317589 TI - Validity of heart-rate based measurements of oxygen consumption during work with light and moderate physical activity. AB - For ergonomic purposes it is useful to quantify the energy expenditure and the level of physical activity imposed on workers. Oxygen consumption (VO2) is often used to calculate energy expenditure and can be used as an indication of physical activity. Twenty-five subjects participated in the study. Oxygen consumption (VO2) in L O2/min and heart-rate (HR) in beats per minute (bpm) were simultaneously measured during different work tasks at each individual's workplace. Ninety-one different work tasks with light or moderate physical activity were included (physical activity was classified by the VO2 measurements). Estimated oxygen consumption (L O2/min) was then calculated by using the HR measurements in bpm combined with individual HR-VO2 equations established in a laboratory. Although heart-rate based estimations of individual oxygen consumption showed relatively low precision, heart-rate measurements in combination with individual exponential HR-VO2 equations can be used to discriminate between work involving light physical activity and work involving moderate physical activity. PMID- 22317590 TI - Regulation in work and decision-making in the activity of public prosecutors in Santa Catarina, Brazil. AB - OBJECTIVE: Was to characterize the relationship between regulation at work and decision processes in the activity of Prosecutors in SC. To this end, it starts with the assumption that the decision-making and regulation are complex phenomena of conduct at work, since the worker makes continuously micro and macro decisions, based on a set of regulations, influenced by contingency and personal variables. PARTICIPANTS: Four Prosecutors participated in this study. METHODS: This was a case study, descriptive and exploratory. For data collection, documents were analyzed, observing the workplace and interviewed key personnel of the institution in order to identify macro and micro organizational factors. Also as a technique for data collection an Ergonomic Analysis of Work. RESULTS: It was found that the work of the Prosecutor presents a set of activities that take place on the basis of coordination and cooperation in a dynamic and unstable environment. The prosecutor's activity, in addition to being the full expression of basic psychological processes of service work, is embedded in a context which, in part, depends and, therefore, encourages and requires choices and referrals by employees, demanding the demonstration of skills and modulating its operative mode. CONCLUSIONS: Processing depends on the idiosyncrasies and the force of circumstances, thus creating a brand, a unique personal style in the work. It is inferred that they are dialectical processes, since they regulate to decide and decide because they are regulated. However, the regular employee builds micro decisions that subsidize an effective decision. Thus, the better the variability of regulation, the greater the variability of decisions. PMID- 22317591 TI - Finding the team for Mars: a psychological and human factors analysis of a Mars Desert Research Station crew. AB - A two-week mission in March and April of 2011 sent six team members to the Mars Desert Research Station (MDRS). MDRS, a research facility in the high Utah desert, provides an analogue for the harsh and unusual working conditions that will be faced by men and women who one day explore Mars. During the mission a selection of quantitative and qualitative psychological tests were administered to the international, multidisciplinary team. A selection of the results are presented along with discussion. PMID- 22317592 TI - Wood, management and dust: analysis of the Context of Production of Goods and Services (CPGS) of an academic woodwork. AB - The CGPS of the woodwork of a public university was observed and analyzed. Apart from what is usual in the field of Ergonomics' studies, it is an academic context, where there is not a direct implication of profit, productivity and clientele. The group tried to sever negative and broadcasted opinions about the place by analyzing it from a different point of view. This work was considered relevant, since it is related to neglect of education and citizenship. For this case study, it was used the Ergonomics Analysis of Work with all workers at the woodwork. The instruments were documental analysis, free observation with photographic register, semi-structured interview with the workers and survey Pontos de Vericacao Ergonomica. The results are presented by the perspective of work conditions, work organization and social-professional work relationship. The present study brought several contributions, such as the complementation of the theory and a new perspective of the analyzed context, o bserved now by the worker's point of view. As a result of the analysis, it was questioned about citizenship and the neglect with the public good, even though the relevant social role that this academic institution plays. In conclusion, the group suggests some proposals that modify positively the CGPS of this academic woodwork. PMID- 22317593 TI - Maximum force levels in different positions of shoulder and elbow. AB - The number of occupational diseases in Mexico is alarming and clearly it is important to do studies with the purpose of improving the design of workstations. The objective of this research is to determine the maximum force levels in different positions of shoulder and elbow. An experiment was conducted with 16 subjects between 18 and 28 years old: 8 male and 8 female. We considered 16 different positions, working with the right and left arm to perform the tasks of pull and push. The tasks consisted of pushing or pulling a dynamometer for a period of 3 seconds as hard as possible. The results were presented in tables. The tables show the mean, standard deviation and range of force levels in different positions. PMID- 22317594 TI - Development of the workflow kine systems for support on KAIZEN. AB - In this paper, we introduce the new workflow line system consisted of the location and image recording, which led to the acquisition of workflow information and the analysis display. From the results of workflow line investigation, we considered the anticipated effects and the problems on KAIZEN. Workflow line information included the location information and action contents information. These technologies suggest the viewpoints to help improvement, for example, exclusion of useless movement, the redesign of layout and the review of work procedure. Manufacturing factory, it was clear that there was much movement from the standard operation place and accumulation residence time. The following was shown as a result of this investigation, to be concrete, the efficient layout was suggested by this system. In the case of the hospital, similarly, it is pointed out that the workflow has the problem of layout and setup operations based on the effective movement pattern of the experts. This system could adapt to routine work, including as well as non-routine work. By the development of this system which can fit and adapt to industrial diversification, more effective "visual management" (visualization of work) is expected in the future. PMID- 22317595 TI - Ergonomics and the inclusion of disabled people in the Brazilian job market. AB - The inclusion of persons with disabilities (PD) has been widely discussed in Brazil. The main purpose of this paper is to identify the contributions of ergonomics in the process of including disabled people in the job market and to discuss the situation in Brazil. It was found that ergonomics is an important tool within organizations. Using it allows space, work stations and tools to be matched workers' needs, including those with disabilities, on behalf of whom it is necessary to adjust the demands of work to their specific needs. However, further research is needed in Brazil on the existing methods of ergonomic intervention for this population in order to suit their needs and optimize potential. PMID- 22317596 TI - Ergonomic intervention methods for inclusion of people with disabilities at work: Brazilian scene. AB - The aim is to identify ergonomic intervention methods used for including people with disabilities (PD) in the Brazilian labor market, with emphasis on discussion of methods to analyze the fit between the worker and the workplace. Methods to evaluate the fit of the worker to the workplace identify the capabilities and limitations of PDs and the demands of work, combining these data, and comparing them, in order to obtain a detailed analysis of the fit were drawn from national and international publications. These show that the use of specific methods for PDs and others focused on the general population. Mutatis mutandis, there is a need for complementary tools to address this segment. Thus, for the Brazilian scenario, it is essential to develop specific methodological tools to assess the capabilities of a PD so that they may better interact with their job. PMID- 22317597 TI - New guidelines for health care for alcohol and drug users and the real work: possible contributions of ergonomics to the restructuring of work and competence development. AB - The study investigated, through a literature review, how the research community has addressed the difficulties experiences by the teams in front of new prescriptions for the treatment of alcohol and drug users in Centers of Psyco social Attention and discusses the relevance of the conceptual and methodological references of Ergonomics for understand and transform work situations. Such studies tend to do an analysis that does not account for variability present in both the workers and work organization and prioritize the analysis of final results of the, disqualifying local inventions due to tasks imposed by policy guidelines. It is estimated that the Ergonomics, considering the diversity of training, learning and experience, contributes to the implementation of media to promote the continued development of competences that can meet the demands of production and expands knowledge about the problems experienced and the possibilities of overcoming them. PMID- 22317598 TI - Support system for management of shares ergonomic. AB - This article discusses the development of a computerized support to demands for treatment of a wide spectrum and diverse nature. Developed under SPM platform (Situacao, Problema e Melhoria), the practitioner seeks to provide an ergonomic aid from the identification and characterization of the processes of analysis demands. The interest of a technological support the practice of ergonomics is a domestic origin, which already features a wide universe. For purposes of this article will be drawn the line defined by the universe in the Federal Public Service occupations within the guidelines set Subsystem Integrated System for Health Care Workers of the Federal Government. The development of this system initially intended to assist the practitioner in ergonomics mapping situations in which the federal public servant has been undergoing for the second time that can classify and then treat them. PMID- 22317599 TI - Ergonomic evaluation of the preparation of cuttings and minicuttings for eucalyptus seedling production, with the use of scissors. AB - This study was conducted in a nursery for eucalyptus seedling production in a forest Company, located in the southern state of Bahia, Brazil. It aimed to evaluate the ergonomic conditions of the preparation of cuttings and mini cuttings with scissors for Eucalyptus seedling production to increase well-being, satisfaction and safety and minimizing the occurrence of occupational diseases, also improving the process efficiency and final product quality. Environmental conditions, levels of noise, postures, RSI risk and physical workload were assessed. The environmental conditions complied with the recommended norms, except at certain times of day, when workers should make compensation breaks. The workers that collect minicuttings presented postures classified as normal by OWAS. On the other hand, the posture of workers dealing with cutting preparation requires corrections in a short run. The workers were subjected to moderate RSI risk due to the high degree of repeatability found. The physical workload was classified as mild, with no need for ergonomic interventions. PMID- 22317600 TI - Slope effect on pushing forces. AB - In some occupations pushing forces are frequent when performed on horizontal ground and are standardized (ISO 2002). In special cases employees are obliged to grow container on slopes and the strains are poorly investigated. The objective of this work is to measure forces required to push garbage container on horizontal and inclined at 0, 4, 11 and 16 % grounds. Sudden and significant increases in heart rate reflect the possible risk of heart overload in long displacements. This study proposes realistic limits and provides a simple and protective tool for a group of employees without distinction of age or gender. These limits can even be reduced to a quasi-linear model where push 200 kg is the maximum for 0% slope and 60 kg for 10% slope. PMID- 22317601 TI - Statistical precision of categorical PATH observations of trunk posture. AB - BACKGROUND: Field studies assessing biomechanical occupational exposures frequently utilize direct observation. PATH (Postures, Activities, Tools, and Handling) is a tool for systematically observing occupational exposures during non-cyclic or long, irregular-cycle jobs. While PATH has been used in many studies, its statistical performance under different data collection strategies has not yet been investigated. The purpose of the current study was to examine this issue. METHODS: Data from labourers performing the four tasks comprising a 'Jacking Pit Construction' operation was extracted from a previously collected data set. Using a probability based re-sampling bootstrap approach, categorical trunk posture exposure data was compared across nine simulated data collection strategies. RESULTS/CONCLUSION: At the operational level, dispersion curves showed consistent trends of increased precision with increased sizes of the data set and curves tended to intersect at the expected value seen in the parent data set. At the task level, curves did not always follow the predicted pattern, highlighting the potential pitfalls of using PATH for infrequent tasks and the striking effect that individual workers can have on group exposure estimates of such tasks. PMID- 22317602 TI - Analysis of the workload of bank tellers of a Brazilian public institution. AB - During the last decades there have been many changes in the banking sector organization. It has been also observed the mutual growing of musculoskeletal and mental disorders. This study investigated the workload of bank tellers at a Brazilian public institution. It was performed the Ergonomic Work Analysis (EWA). Three employees participated in this study. During the analysis process, three research instruments were applied: Inventory of Work and Risk of Illness, Yoshitake Fatigue Questionnaire and Nordic Musculoskeletal Questionnaire, beyond the realization of footage recordings and the self-confrontation. The results indicated the existence of an excess of workload on the evaluated workstations, mainly in relation to mental order constraints, that overlaps the physical aspects. Thereby it was found that the employees tend to adopt strategies trying to reduce the impacts of the excess of workload, in order to regulate it. PMID- 22317603 TI - Body postures versus production requirements - the case of a fiberglass parts factory. AB - This study aimed to perform an ergonomic analysis in a fiberglass parts factory. For this purpose, was used the methodology of Ergonomic Work Analysis (EWA). At the end of the study it was possible to identify some ways to the development of improvements in order to contribute to the transformation of working conditions in the sector analyzed. PMID- 22317604 TI - A novel wearable measurement system for ambulatory assessment of joint loading in the occupational setting. AB - It is know that biomechanical overexposure of the joints is an important cause of occupational injuries. This paper presents a novel wearable measurement system for automated assessment of joint loading in the occupational setting. The wearable measurement system consists of a full body inertial sensor motion capture system which can be worn under the clothes and shoes instrumented with 3D force sensors (ForceShoes). Promising results have been found for the performance of the inertial sensor system and the ForceShoe, separately. Validation experiments are in preparation in which the performance of the combined measurements system will be tested in the laboratory by comparing the assessed joint loading to the joint loading assessed by a conventional state-of-the-art lab-based method. PMID- 22317605 TI - Using practical ergonomic evaluations in the restaurant industry to enhance safety and comfort: a case study. AB - Restaurant employees must deal with loud noise, busy environments, difficult customers, heavy, awkward, sharp, and hot objects, repetitive motions, and stress on various joints, all of which can lead to fatigue, sudden accidents, and longterm musculoskeletal injury. The goal of this case study was to assess the risk of injuries and accidents from conducting various tasks in the restaurant, specifically carrying/lifting, table management, and polishing silverware. The nine participants were servers at a local country club restaurant. Physical workload was measured by a scale of physical exertion. Cognitive workload was assessed, as well as cumulative trauma disorder risk. Overall results show that there is sufficient risk in some of the tasks to warrant concern. Specific results are discussed, as well as recommendations for improved safety. PMID- 22317606 TI - Ergonomic assessment of porridge roaming sale system. AB - This paper makes suggestions for the realization of an ergonomic intervention, guided by the method of Moraes and Mont'Alvao (2009), in the system of street vending of porridge, to improve the working conditions of this sales segment. Specifics are given about this practice and its problems, from ergonomic analysis comes to suggestions for improvements to be applied to a new system. PMID- 22317607 TI - Effects of a labor gym program in mental workload of workers from rectory of UNIOESTE. AB - The present work is a quality-quantitative study of cause-effect type. The objective of this study was to investigate the effect of a Labor Gym (LG) program in mental workload of workers from rectory of the Universidade Estadual do Oeste do Parana (Unioeste) Cascavel. The sample consisted of 35 employees. For data collection, it was used the NASA-TLX questionnaire to evaluate the mental workload of employees. Then, the participants performed sessions of LG, totaling 20 classes. After this period the employess were re-evaluated. To characterize the sample, data were tabulated and a descriptive analysis was performed using the SPSS 15.0. The interpretation of the NASA-TLX questionnaire was based on its own methodology. Before the LG sessions, the total average dimensions analyzed was 79 (sd: 11,05), representing a high rate of mental workload. After the period of LG, the total average of final mental workload decreased, but it remained with a high rate (x:75, sd: 13.42). In relation to the comparative analysis of the initial and final averages of mental workload, by t test (bipolar), there was no significant difference (p = 0.071668). PMID- 22317608 TI - Analysis on the relationship between the school furniture and the work surface lighting and the body posture of public Middle School students from Joao Pessoa, Paraiba, Brazil. AB - The main objective of this study is to evaluate the impact of school furniture and work surface lighting on the body posture of two public Middle School students from Paraiba (Brazil). The target population included 8th grade groups involving 31 students. Brazilian standards for lighting levels, the CEBRACE standards for furniture measurements and the Postural Assessment Software (SAPO) for the postural misalignment assay were adopted for the measurements comparison. The statistic analysis includes analyses of parametric and non-parametric correlations. The results show that the students' most affected parts of the body were the spine, the regions of the knees and head and neck and about 90% of the students presented postural misalignment. The lighting levels were usually found below 300 lux, below recommended levels. Such results indicate the need of investments in more suitable school furniture and structural reforms aimed at improving the lighting in the classrooms, which could fulfill the students' profile and reduce their complaints. PMID- 22317609 TI - Ergonomic considerations in school environments - the need for widening the scope. AB - Behaviour patterns specific to children pose them at greater risk of environmental hazards than adults. Ergonomics is the science of matching human interaction with the proximate environment. Conventionally ergonomic principles were applied on adult work places to ensure safety of the working environment. With emerging scientific evidence, school environments are being a focus to apply ergonomic principles. Children spend more time within schools during critical developmental stages of their life. Everybody feels that the schools are safe places, but they are not. A multitude of ergonomic hazards have been identified in school settings. Widespread mismatches between anthropometry and school furniture, heavy schoolbag carriage and unhealthy bag behaviour are significant. Negative effects range from general tiredness, musculoskeletal pains, spinal deviations, shoulder level shifts, injuries and psychological disturbances. There are fragmented efforts to widen ergonomic concepts to health care professionals and other stakeholders of child health. Addressing ergonomic issues will ensure that children, the future productive generation contributing to economic growth and development of a country, are provided with opportunities in a healthy environment. This paper emphasizes the need for a concerted effort on widening the scope of ergonomics to cater for the evolving demand. PMID- 22317610 TI - Ergonomic adequacy of the baby nursery of child development center located in UFSC - Florianopolis. AB - A study in the educators' work station at baby nursery of NDI/UFSC, located in Florianopolis, was conducted using the Work Ergonomic Analysis methodological tool. The demand considered was the educators' physical exhaustion caused by the weight carried when taking care of the babies, the postures assumed during the labor activity and the spatial arrangement of the baby nursery. Thinking ergonomically, the spatial arrangement is directly associated to three factors: the formal aspect of the environment, the esthetic aspect including colors and finish quality and the ease of understanding involved in the baby nursery labor. By the ergonomic adequacy it is possible to assert that if were established better conditions of posture and comfort for the educators, as well as satisfactory technical and operational information to carry out the activities, greater safety and welfare would be provided to the babies, the main focus of the work. PMID- 22317611 TI - Sleep patterns and sleepiness of working college students. AB - The double journey (work and study) may result or aggravate health problems, including sleep disturbances, as observed in previous studies with high school students. The aim of this study is to analyze the sleep-wake cycle and perceived sleepiness of working college students during weekdays. Twenty-three healthy college male students, 21-24 years old, working during the day and attending classes in the evening, participated in this study. During five consecutive days, the students filled out daily activities logs and wore actigraphs. Mean sleeping time was lower than 6 hours per night. No significant differences were observed in the sleep-wake cycle during the weekdays. The observed lack of changes in the sleepwake cycle of these college students might occur as participants were not on a free schedule, but exposed to social constraints, as was the regular attendance to evening college and day work activities. Sleepiness worsened over the evening school hours. Those results show the burden carried by College students who perform double activities - work and study. PMID- 22317612 TI - Global healthy backpack initiatives. AB - Schoolbag use by children is a global common concern.. Children carry school books and other amenities in their school bags. Global evidence indicates that daily load carried by school children may have negative health implications. Backpack as a school bag model, is the healthiest way of load carriage for school children. Several initiatives have been launched world over to minimize unhealthy consequences resulting from schoolbags. Based on a situation analysis, Sri Lanka implemented a national healthy schoolbag campaign by joint efforts of Ministries of Health and Education. Actions were contemplated on; strategies for bag weight reduction, introduction of an ergonomically modeled schoolbag and bag behaviour change. New strategies were introduced with awareness campaigns to policy makers, bag manufacturers, parents, teachers and children. Four million schoolchildren benefitted. In 2000, the backpack strategy of "Pack it Light, Wear it Right" was started as a public health initiative in the United States by the American Occupational Therapy Association (AOTA). Over the last eleven years, thousands of occupational therapy practitioners and students participated in educational programs and outreach activities. In 2004, modeled after the success AOTA initiative, the Icelandic Occupational Therapy Association launched a national backpack awareness initiative. This article shares examples of practices that could be implemented in any context to the promote health of children. PMID- 22317613 TI - Manual bamboo cutting tool. AB - The paper presents the development of a cutting tool guide, specifically for the harvest of bamboo. The development was made based on precepts of eco-design and ergonomics, for prioritizing the physical health of the operator and the maintenance of the environment, as well as meet specific requirements of bamboo. The main goal is to spread the use of bamboo as construction material, handicrafts, among others, from a handy, easy assembly and material available tool. PMID- 22317614 TI - The correlation between thermal comfort in buildings and fashion products. AB - This article is about thermal comfort in the wearable product. The research correlates fashion and architecture, in so far as it elects the brise soleil - an architectural element capable of regulating temperature and ventilation inside buildings - as a study referential, in trying to transpose and adapt its mechanisms to the wearable apparel. PMID- 22317615 TI - The importance of ergonomics in the design conceptual process: Daciano da Costa - a case study on practicing and teaching. AB - This paper, which stems from a developing research project, aims to disseminate among the international scientific community the thought of Daciano da Costa (1930-2005) given the importance he conferred to Ergonomics, throughout his teaching career and his professional practice as a reference figure in the Design of the twentieth century in Portugal. We focus on the important role played by Ergonomics within the conceptual Design process, through the case study Daciano da Costa.What Daciano brought to the practice and teaching was a modernization of processes, a new perspective on the emerging themes of design, like ergonomics. Daciano believed that designing was providing a service. This task was understood as the building of a relationship with users. One of his distinguished features was the particular attention he paid to the unique aspects of the scale of proximity: the scale of the hand, of the immediate gesture, of the body. As a professor he insisted not so much on the end product, but rather on the recognition of the research process and how it was conducted. When designing, developing and supervising the exercises he set, ergonomic factors were one of his main concerns. PMID- 22317616 TI - The incubator hospital from the viewpoint of ergonomic. PMID- 22317617 TI - Usability of car stereo. AB - Automotive sound systems vary widely in terms of functions and way of use between different brands and models what can bring difficulties and lack of consistency to the user. This study aimed to analyze the usability of car stereo commonly found in the market. Four products were analyzed by task analysis and after use reports and the results indicate serious usability issues with respect to the form of operation, organization, clarity and quality of information, visibility and readability, among others. PMID- 22317618 TI - The suitability of the design of handbags to the tropical climate. AB - This work encourages the exercise of consideration, observation and critical reading of the design of handbags and the relation to the conditions imposed by tropical climate. Our purpose is to highlight some critical and conceptual thoughts on the matter of the design of fashion accessories in Brazil, ergonomics and aesthetic- functional relation. Through physical concepts is possible to propose consistents solutions compatible with the reality of the costumers living on Brazilian coast. PMID- 22317619 TI - Seniors and technology, ergonomic needs and design considerations. AB - This work is based on the ergonomic approach and the principles of universal design, with the aim of establishing the cognitive design features that interfaces must comply, for older adults achieve a good performance during their interaction with technological aids. Describes the analysis of exploratory experiences with a group of 17 older adults was aimed first to establish the main barriers to implementation that arise during these activities, and secondly to set the variables to be addressed and the procedure required to develop depth study, where the relationship establish between the quality of the stimuli and the level of performance achieved in the implementation of older adults with interfaces, observing each of the cognitive functions that promote independence, attention, motivation, memory these processes. The study in depth, looking for describe gaps and mismatches encountered during execution, which hamper the harmonious interaction processes through participatory methodological approach that allows to specify requirements for the creation of stimulating interfaces for cognitive skills and committed with the levels of autonomy of the elderly. PMID- 22317620 TI - Inclusive design in the implementation of projects for schools modernization in Portugal - case studies. AB - The Project for Schools Modernization taking place in Portugal, with an estimated total investment of 2450 million for the intervention in the first 205 schools, provide the reclassification of 332 secondary schools by 2015. One of the questions we can pose is if the authorities and the teams of architects selected to design these schools considered fundamental for the correctness of architectural barriers within the school and its accessibility the implementation of standards and principles of inclusion of children/teenagers with special needs within their school environment. As most of the projects are already being implemented, the main aim of this paper is to present the outcomes of a comparative analysis and synthesis of six schools located in the northern part of the country. This analysis occurs from the of Participatory Design perspective which appeals to the experience of the disable children to look (or evaluate) the negative and positive factors in terms of physical space, interpreted by inclusive design rules and orientations. Therefore, the evaluation of schools modernization project, and its discussion, is central for the understanding how these children are addressed in projects which are directed at them. PMID- 22317621 TI - User-Centered Design (UCD) applied to the identification and modification of unsustainable practices. AB - Metropolitan Autonomous University, Cuajimalpa Unit (UAM-C) has as one of its main themes, researching and teaching of sustainability. In it, the Bachelor of Design program considers among its teaching approaches those of User-Centered Design and Eco-design as important issues, this explains the interest in addressing the areas in which both approaches can be articulated to reduce unsustainable practices through the design of messages, environments and products. PMID- 22317622 TI - Perceptual aspects of the use of faucets (taps). AB - This paper presents an assessment with simulated activities with the aim of analyzing the perception of ease / difficulty of the use of faucets (taps) handles by 180 Brazilian adults. Five different handles faucets were activated for subsequent collection of perceptual data. The procedures were based on main recommendations for biomedical ethics and human research. The results indicate that handles with levers are significantly (p <= 0.05) easier to use. The most difficult are characterized by not having support points for the rotation (levers) or more points of pressure concentration in the hand. PMID- 22317623 TI - Colour, vision and ergonomics. AB - This paper is based on a research project - Visual Communication and Inclusive Design-Colour, Legibility and Aged Vision, developed at the Faculty of Architecture of Lisbon. The research has the aim of determining specific design principles to be applied to visual communication design (printed) objects, in order to be easily read and perceived by all. This study target group was composed by a selection of socially active individuals, between 55 and 80 years, and we used cultural events posters as objects of study and observation. The main objective is to overlap the study of areas such as colour, vision, older people's colour vision, ergonomics, chromatic contrasts, typography and legibility. In the end we will produce a manual with guidelines and information to apply scientific knowledge into the communication design projectual practice. Within the normal aging process, visual functions gradually decline; the quality of vision worsens, colour vision and contrast sensitivity are also affected. As people's needs change along with age, design should help people and communities, and improve life quality in the present. Applying principles of visually accessible design and ergonomics, the printed design objects, (or interior spaces, urban environments, products, signage and all kinds of visually information) will be effective, easier on everyone's eyes not only for visually impaired people but also for all of us as we age. PMID- 22317624 TI - A proposal for an ergonomic redesign for a mixer Mondial B-02. AB - This research aimed to redesign an appliance based on the biomechanical aspects in applied ergonomics. The product chosen for analysis was the household mixer, it is readily found in most homes of several families. The study enabled the identification of several potential risks and proposed biomechanical ergonomic solutions for each. Finally, it was possible to redesign the handle of the mixer, making it suitable form and human use. PMID- 22317625 TI - Cognitive ergonomics and production information systems under the gaze of interdisciplinary design or industrial design. AB - The core of this work involves the study of cognitive ergonomics and production of Information Systems under the interdisciplinary of the Design or Industrial Design. It is assumed that in the dynamics of human and the systems, mediated by systematic technology, there are constant changes in social perceptions, that alter the shape of the subject dealing with the real world, concrete, adopting a pseudo-idea of the evolutionary process. Attentive to the interdisciplinary and transdisciplinary groups as agents of this process, points to the danger of the emergence of the myth of innovation as a solver of social problems and suggests new ergonomics as a contributor in a different way of thinking the humanization beyond of the XXI century. PMID- 22317626 TI - Postmen activity's analysis. AB - This study examines the postmen activity and the bag used in their task, which should transport the weight without affecting the locomotor system and the attitude of the worker. Studies were conducted on the activity of the postmen and transportation of loads, analyzing functional and ergonomic aspects of load distribution, as well as surveys with users, which made it possible to verify and prove the problems presented. Thus, the following work was developed in order to demonstrate the importance of applying an ergonomic product design. PMID- 22317627 TI - Analysis of ergonomic furniture made of wood and sub-products from renewable forests. AB - The furniture ergonomic evaluation was carried out through the use of questionnaires and forms in industries. For the ergonomic product analysis, it was used the methodology "Object Ergonomics - Ergonomic System Technical Reading" (design goals and management actions), and measurements of products. The values achieved were compared with the standard dimensions, and the compliance or non compliance of the furniture to it was assessed. In relation to the dimensions of the bed, the following variables did not comply with the norms: external and internal length, external and internal width, height and width of the sidebar and distance to the floor. The dimensions of these variables were above the recommended values. The double bed was inadequate for management actions and maintenance. Since the kitchen cabinet is a product that went through physical testing and follows national standards; the finish used is powder coating. The kitchen cabinet proved to be appropriate in all design requirements and for management actions. Both furniture pieces were inadequate, considering the difficulty for maintenance when a product or part of it was damaged. It was recommended the creation of regulatory standards for the production of safe and comfortable furniture. PMID- 22317628 TI - Design considerations to improve cognitive ergonomic issues of unmanned vehicle interfaces utilizing video game controllers. AB - Unmanned (UAVs, UCAVs, and UGVs) systems still have major human factors and ergonomic challenges related to the effective design of their control interface systems, crucial to their efficient operation, maintenance, and safety. Unmanned system interfaces with a human centered approach promote intuitive interfaces that are easier to learn, and reduce human errors and other cognitive ergonomic issues with interface design. Automation has shifted workload from physical to cognitive, thus control interfaces for unmanned systems need to reduce mental workload on the operators and facilitate the interaction between vehicle and operator. Two-handed video game controllers provide wide usability within the overall population, prior exposure for new operators, and a variety of interface complexity levels to match the complexity level of the task and reduce cognitive load. This paper categorizes and provides taxonomy for 121 haptic interfaces from the entertainment industry that can be utilized as control interfaces for unmanned systems. Five categories of controllers were based on the complexity of the buttons, control pads, joysticks, and switches on the controller. This allows the selection of the level of complexity needed for a specific task without creating an entirely new design or utilizing an overly complex design. PMID- 22317629 TI - Macroergonomic intervention for work design improvement and raw materials waste reduction in a small footwear components company in Rio Grande do Sul-Brazil. AB - This article presents a macroergonomic intervention carried out in a small footwear components company located in the state of Rio Grande do Sul, Brazil. The company's demand was related to the waste of the expensive raw-material (thermoplastic polyurethane or TPU) used to manufacture the components (high heels pegs). According to the managerial staff, the waste was workers responsibility due to the craft characteristic of the process. A participative method was used to evaluate the problems, propose and implement solutions, as well as evaluate their impact on the workers and the Company. Improvements in the work conditions resulted in increase of workers' satisfaction with the work and in 31.5% waste reduction. PMID- 22317630 TI - Study about upper limb on highly repetitive work in maquila operations. AB - Industrial work is a very active sector in the economy of countries; an important part of people's work is done using the upper extremities. The purpose of this project is to characterize the effect of upper extremity work, analyze its relationship with the hand strength and the presence of fatigue and develop a model with the ability to estimate recovery times for the shoulder using variables different from the biomechanical variables. PMID- 22317631 TI - Preponderance and possible factors associated to musculoskeletal symptoms in metals industry workers. AB - The objective of this study was to determine the prevalence of complaints of musculoskeletal pain in workers following the metallurgical establishing a relationship with the sociodemographic profile and perception of professionals about the cause of symptoms. A descriptive cross-sectional study was conducted in the following metallurgical enterprises in the city of Curitiba, Brazil. The sample consisted of 50 individuals. The instrument used for data collection was the "Nordic Questionnaire of musculoskeletal symptoms" including demographic data and verifying the level of significance (0.05). There was a prevalence of low back pain, hip and lower limbs (92%), especially those who work more than one year, and 82% reported relationship between pain and work. The symptoms in the lumbar region grouped the dorsal region was more related to activity performed with the p-value of 0.000. The possible relationship between pain and the work reveals the need for an ergonomic program that allows improved quality of life for the metallurgical. PMID- 22317632 TI - The ergonomics approach for thin film transistor-liquid crystal display manufacturing process. AB - The thin film transistor-liquid crystal display (TFT-LCD) has been used all over the world. Although the manufacture process of TFT-LCD was highly automated, employees are hired to do manual job in module assembly process. The operators may have high risk of musculoskeletal disorders because of the long work hours and the repetitive activities in an unfitted work station. The tools of this study were questionnaire, checklist and to evaluate the work place design. The result shows that the participants reported high musculoskeletal disorder symptoms in shoulder (59.8%), neck (49.5%), wrist (39.5%), and upper back (30.6%). And, to reduce the ergonomic risk factors, revising the height of the work benches, chairs and redesigning the truck to decrease the chance of unsuitable positions were recommended and to reduce other ergonomics hazards and seta good human machine interface and appropriate job design. PMID- 22317633 TI - Interface of drug use. AB - Packaging and labeling play a crucial role awhile protecting medicaments and transmitting a range of crucial information to the users. Taking into account the scarcity of specific studies in this area, it was considered great the need for a comprehensive survey about customers' satisfaction when handling these containers. PMID- 22317634 TI - The effect of visualization method on the performance of simulated microsurgery tasks. AB - The operating microscopes may be a significant cause of fatigue and discomfort in surgeons. The need for the microscope to be placed over the operating field forces surgeons to remain at the microscope's eyepieces at an uncomfortable posture for the entirety of the surgery. This study compared the effects on microsurgical task performance for four visualization methods: a monocular microscope, a binocular microscope, a three-dimensional (3D) flat-panel television display and a two-dimensional (2D) flat-panel television display. Eleven subjects each performed two microsurgical tasks and their performance was documented by video camera. The statistical analysis performed indicated utilization of the microscope as a visualization method increased subject performance. No significant difference in performance between the 2D and stereoscopic visualization methods. PMID- 22317635 TI - Static load in the nursing profession; the silent killer? AB - Traditionally back pain in the nursing profession is associated with heavy lifting of patients. Although there is a strong relationship between heavy loads on the spine and lifting patients, literature indicates that there is a major factor that should not be underestimated: static load. Static load can be defined as the result of static, not moving, not dynamic, working positions. For example when a caregiver is washing a patient on a bed which is too low, her back is in a static (bended) stooped position up to several minutes. Exposure to static load is an underestimated silent killer of nurses musculoskeletal system . There is evidence from this cross-sectional study that static load can be reduced by a combination of introducing the right equipment, creating awareness and education. PMID- 22317636 TI - An international validation study of the care thermometer: a tool supporting the quality of ergonomic policies in health care. AB - Occupational back pain among nurses leads to high costs and personal suffering for nurses. It is difficult to assess the success of such initiatives and to monitor results in a practical way. Such a practical monitoring and web-based instrument was developed. This Care Thermometer (CT) allows the users to assess the current situation in their facility today, and, with regular use, it can help to track progress over time. The Care Thermometer is a further step in the development of the TilThermometer, a validated assessment tool that is used on a large, national scale in The Netherlands. The claims of the newly developed Care Thermometer are ambitious and an international validation study was performed in four countries: the UK, USA, Germany and the Netherlands. The instrument appears to be sufficiently valid, useful and practical. There are however some points to keep in mind when interpreting the results of the CT. Especially a careful, punctual and stringent data collection phase is crucial for accurate and useful results. Some recommendations to further improve the practical use both for the design of the instrument and the process of data-collection and -entering are given. PMID- 22317637 TI - Flying through the hospital: efficiency and safety of an ergonomic solution. AB - In hospitals many horizontal transfers (from stretcher to bed etc.) are performed from the moment a patient is admitted (f.e. with an ambulance) through examination departments all the way to the wards. These transfers can be very strenuous and solutions may be to use a special lifting device that accompanies the patient on this route: a stretcher sling This is a specially designed disposable lifting sling for horizontal transfers and repositioning, the sling can easily be connected to a ceiling or mobile lift. The ambulance service, two hospitals and a manufacturer decided to study the effects. The stretcher sling travels with the patient. Does this provide an ergonomically sound solution and is this an effective and efficient solution? The results were positive, but a behavioral change was also necessary. PMID- 22317638 TI - Ergonomics in the operating room. AB - Surgical staff is considered to have several ergonomic risk factors, but their physical workload and musculoskeletal health have seldom been evaluated. Clinical examinations of neck and upper extremities were performed in 99 theatre nurses and 93 assisting nurses, all females. Their physical workload was assessed by questionnaire, and by technical measurements of postures, movements and muscular load in subgroups of both categories. The prevalences of diagnoses in neck/shoulders were not remarkably high in the nurses, compared to other occupational groups. In elbows/hands though, the prevalence was rather high among assistant nurses, 13 vs. 5 % in theatre nurses; POR 3.0 (CI 95 % 1.0 - 8.9). Theatre nurses experienced prolonged static postures in the questionnaire, whilst assistant nurses reported high physical load. Accordingly, the technical measurements showed more strenuous working postures in the theatre nurses, but lower wrist angular velocities. The time proportion of muscular rest in m.trapezius was rather high in both groups. Although both groups had some stressful loads they had relatively low prevalence of diagnoses in neck/shoulders. The high proportion of muscular rest may be protective. The elevated risk of elbows/hands diagnoses among assistant nurses may be explained by strenuous work tasks of short duration. PMID- 22317639 TI - Evaluation of the health risks to garment workers in the city of Xambre-PR, Brazil. AB - This study evaluated the risks for cardiovascular disease and the life habits of garment industry workers in northwestern Parana state, Brazil. The following parameters were assessed: body composition, cardiorespiratory fitness, eating habits and physical activities by garment industry workers. Cardiovascular risk was observed in some of the studied subjects, in the form of high BMI and reduced maximal oxygen uptake. The development of a workplace quality-of-life program is suggested, aiming to stimulate the development of physical activities to improve the cardiovascular conditioning of workers. PMID- 22317640 TI - Designing the care environment in hospitals and nursing homes: a pilot for a new and reliable method for determining the optimum space to live in and work in. AB - One of the major problems encountered in health care during the process of implementing ergonomic changes is the lack of space. There is often not enough space to work with larger equipment like patient lifters and shower chairs or other medical devices necessary in a preventive program. This leads to undesirable extra physical load for nurses. Therefore it is imperative that in the process of designing the health care environment ergonomic considerations are taken into account. A method to assess the optimum size and shape of the space required is developed and the value of the method is tested in a pilot setting. The pilot is currently underway and the results will be presented on the final poster. PMID- 22317641 TI - The influence of an abdominal support for a dental stool in the distributions and electrical activity of the longissimus and the superior trapezius muscle in dentists. AB - This study evaluated the influence an abdominal support attached to a traditional stool, of those used by dentists, has on the body's distribution of the electrical activity of the superior trapezius and the longissimus thoracic muscles of dental students during the execution of a clinical procedure. The results showed no significant difference in the body's distribution in the seat and backrest, but did reveal there was a weight discharge of 3.1 +/- 1.9% of dentist's body weight in the abdominal support. The 9 o'clock position proved to be the best position to perform clinical procedures. It was also observed that the position was closer to the body's axis. PMID- 22317642 TI - Assessments of patients with a 5-category or a 3-category practical classification system: validity and practicality. AB - In order to implement preventive programs to prevent back pain in nurses, assessments of the degree of passivity and mobility of patients is imperative. After all, the load in health care ergonomics, is often the patient. The degree of cooperation or resistance determines the load on the back for the nurses and the necessity of the use of lifting devices like patient lifters or sliding sheets. These assessments must be done in both a practical and a reliable way. For this purpose a 3-category and a 5- category system to assess the degree of patient mobility and passivity was developed and tested. The results are presented on the poster. PMID- 22317643 TI - The businesscase for ergonomic changes in health care: calculating and predicting financial outcome for ergonomic changes and innovations in health care: interactive businesscase modelling. AB - Research can point to new opportunities and assist in the development of valid business cases to help nurse managers plan change and allocate their budgets to the most promising interventions. These business cases and their results will, in turn, pave the way for more in depth and more fundamental research into implementation processes. It will add to the body of knowledge of intervention research and ultimately hopefully also add to our understanding of why ergonomic interventions in the workplace will or will not be effective and what the impact of financial constraints is. It is difficult to develop and design a valid businesscase. This poster will present one of the possible strategies to develop one. PMID- 22317644 TI - Study on workloads of human care worker with the introduction of IT system - the characteristics of work loads by observational research and the suggestions for KAIZEN. AB - The purpose of this study was to clarify the characteristic of workloads on human care worker with the introduction of IT system, and suggested the support measures for KAIZEN in Japan. The investigation method is workflow line and hearing with a focus on work observation. The objects were 8 human care workers of the acute hospital that introduced an electronic system. By the introduction of the electronic chart, the nurse station sojourn time decreased, sickroom sojourn time increased, and time about direct nursing care to a patient increased. In addition, access to patient information became easy, and the offer of the health care service based on correct information came to be possible in real time. By The point of workflow line, it was effect that moving lengths decreased in order to install the electronic chart in patients' rooms. Though, it was a problem that it hasn't formed where to place the instruments such as sphygmomanometer, clinical thermometer and others. PMID- 22317645 TI - Experimental study of assistant aids and new nursing method in nursing care work. AB - This study seeks to evaluate the effect of regular and new nursing methods in nursing care work. Nursing care work often causes low back pain in nursing care worker. The principle of not lifting when transferring patients has been proposed as one way to prevent low back pain. This principle incorporates the use of the patient's strength and assistant aids. A sliding seats and transfer boards have been proposed as assistant aids for the transferring patients. It is necessary to evaluate the effectiveness of these assistant aids in preventing low back pain. Ten subjects performed two tasks in this experiment. Five were nursing experienced persons and five were the inexperienced. EMG results indicated that the new nursing method was less stressful than the methods. A questionnaire revealed that the new method was evaluated more highly than the regular method. Based on these results, we propose that a sliding seats and transfer boards be used in nursing care work. PMID- 22317646 TI - Human factors methods to reduce medication error: using task analysis in a pediatric and adult pharmacy. AB - Medication error is an issue that no hospital is immune from, leading to 7,000 deaths and 1.3 million patient injuries each year. The purpose of this study was to decrease the risk and occurrence of medication errors by analyzing the hospital pharmacy. Task analyses were performed and it was found that communication, expectation, and procedural issues were leading to the occurrence of the most common type of medication error in the pharmacy. Recommendations were made to improve the process and reduce the occurrence of this type of error. PMID- 22317647 TI - The ambivalence of the work of the hotel managers: an approach to ergonomics. AB - This article uses the contributions of ergonomics to understand the work performed by hotel managers. The concern to understand the job of managers is something new in the ergonomics and few studies address this issue, especially in what concerns the work of hotel managers and its aspects of performance and health, which is the focus of this article. Through a literature review on the subject, it is sought to understand the managers' work activity, the impacts on their health and their organizational performance, as managers take an ambivalent position in organizations, since they have to deal directly with the demands of upper and lower hierarchies in a context of high competition, organizational changes and user requirements. It is then inferred there is a risk of increased work density for managers, bringing negative consequences to their health and organizational performance. This phenomenon, still poorly covered by ergonomics, contributes to a certain invisibility of the manager's work in society as a whole, when the manager may suffer from health problems, which are also common in certain populations of workers who do not take the managerial function. PMID- 22317648 TI - Emotions and leadership. Reasons and impact of emotions in organizational context. AB - Emotions as reasons for dissatisfaction, decreasing job performance or physical and mental strain at work are becoming more and more important. Especially psycho social interactions with conflicts between employees and managers, caused by leadership behavior, as a source of negative emotions are relevant in this context. Which relevance emotions can have in order to influence human behavior and in order to influence work climate will be demonstrated by two qualitative field surveys in the automotive and the energy sector. The study in the energy sector will explain which leadership behavior fosters an improved employee behavior concerning occupational health and safety. A second study in the automotive industry shows that leadership behavior which causes positive emotions is essential for successful teamwork. PMID- 22317649 TI - Harassment at work? Empowerment and autonomy as coping strategies of young workers. AB - There is a considerable number of researches about workplace violence, but few relate young workers and work harassment. This study aimed to investigate the reported perceptions of young apprentices and trainees about moral harassment at work and related coping strategies. Forty adolescent workers (22 men and 18 women) between 15 and 20 years old who received training by a non-governmental organization in Sao Paulo, Brazil, participated in the study. Data collection included individual and collective interviews. It was used an in-depth semi structured interview protocol. The discourses were analyzed using the hermeneutic dialectic frame. Results showed that young workers reported little or no knowledge of strategies to cope with moral harassment at work, showing vulnerability to the effects of aggression. Effective coping strategies at work should embrace two important concepts of health promotion: empowerment and autonomy. PMID- 22317650 TI - The relationship between heart rate as an indicator of work hardness and results of dynamometry. AB - Heart rate is associated with work hardness and increase linearly with its increasing. In the average of energy consumption, heart rate measurement is simple but non-accurate method for calculation of work hardness. Our purpose in this research was to evaluate the relationship between heart rate and dynamometry results with hypothesis of work hardness effectiveness on the human power. This study was conducted on 102 porcelain workers. Participants were selected randomly. The research tools include stethoscope, the dynamometer. Heart rate, and pinch, grip, and back-leg-chest force were measured and relationships between variables were analyzed with Pearson correlation test and independent T-test using Spss 16 software. The average heart rate of participants were 4.11 +/- 1.79 with minimum 60 and maximum 120. The average force of pinch, grip, and back-leg chest were 8.9 +/- 3.20, 4.2 +/- 4.5 and 9.36 +/- 6.55, respectively. Work hardness for 3.86% of workers were light, 7.12% were moderate and 1% were heavy. Pinch, grip, and back-leg-chest force relation with heart rate were not significant (r=0.01, p=0.85), (r=-0.03, p=0.74), and (r=0.05, p= 0.59), respectively. There was no correlation between heart rate and work hardness. So we can't use the dynamometry results to determine of work hardness. PMID- 22317651 TI - The municipal solid waste and the quality of life of collectors of recyclable materials in Juiz de Fora, Minas Gerais. AB - The generation growing and diversified of Municipal Solid Waste is configured as an environmental problem, economic and social deterioration, especially, by application of inappropriate management of them. Faced with this urban context, the research in development presents as specific objective assessment of the quality of life of the gatherers of recyclable materials were active in the city of Juiz de Fora, in the brazilian state of Minas Gerais. In addition, the objective is, still, the recognition of the activity of sorting performed by "scavengers" in order to maximize the reduction, reuse and recycling energy and material waste daily. The proposed methodology is based on the application of the questionnaire Word Health Organization Quality of Life (WHOQOL-100), prepared by the World Health Organization, in order to value the quality of life of the gatherers of recyclable materials, involved, even in educational workshops in order to discuss and organize strategies of health care and scouting to the basement to public policies. PMID- 22317652 TI - Cognitive-ergonomics and instructional aspects of e-learning courses. AB - This paper presents an analysis of cognitive-ergonomic aspects of e-learning courses, offered by an organism from Brazilian Public Administration. The Cognitive Ergonomic studies conductive and cognitive aspects concerning to the relation between human, physics elements and social elements of the work space. From that usability aspects were evaluated by these points: i) visualization; ii) text comprehension lecture; iii) memory; iv) interface; v) instructional design; and vi) attention and learning. That survey is characterized as having been applied using the following techniques: (1) bibliographic survey, (2) field survey and (3) analysis of the documents. It was chosen the semi-structured questionnaire as the main method of data collection. About the interacting with artifacts, the interface of the courses is classified as direct engagement, because it allows the user to get the feeling that acts directly on the objects. Although the courses are well-structured they have flaws that will be discussed below. Even with these problems, the courses have a good degree of usability. PMID- 22317653 TI - The ambient intelligence for the sake of accessibility in residential projects: a proper study to the Brazilian scene. AB - The concept of Ambient Intelligence consists of intuitive interfaces embedded in everyday objects that interact with the user and function in an integrated and discrete generating and transmitting information. This article has as objective to present applications that when focused on accessibility criteria, can contribute to the work of architects during the design of residential projects. In Brazil, pioneering projects are already being developed and the use of Ambient Intelligence systems are already widespread, both by private and public, however much care technologies developed in other countries. PMID- 22317654 TI - Proposal of digital interface for the system of the air conditioner's remote control: analysis of the system of feedback. AB - Develop a proposal of digital interface for the system of the remote control, that functions as support system during the manipulation of air conditioner adjusted for the users in general, from ergonomic parameters, objectifying the reduction of the problems faced for the user and improving the process. PARTICIPANTS: 20 people with questionnaire with both qualitative and quantitative level. Linear Method consists of a sequence of steps in which the input of one of them depends on the output from the previous one, although they are independent. The process of feedback, when necessary, must occur within each step separately. PMID- 22317655 TI - The effects of exercise reminder software program on office workers' perceived pain level, work performance and quality of life. AB - In direct proportion to current technological developments, both the computer usage in the workplaces is increased and requirement of leaving the desk for an office worker in order to photocopy a document, send or receive an e-mail is decreased. Therefore, office workers stay in the same postures accompanied by long periods of keyboard usage. In recent years, with intent to reduce the incidence of work related musculoskeletal disorders several exercise reminder software programs have been developed. The purpose of this study is to evaluate the effectiveness of the exercise reminder software program on office workers' perceived pain level, work performance and quality of life. 39 healthy office workers accepted to attend the study. Participants were randomly split in to two groups, control group (n = 19) and intervention group (n = 20). Visual Analogue Scale to evaluate the perceived pain was administered all of the participants in the beginning and at the end of the study. The intervention group used the program for 10 weeks. Findings showed that the control group VAS scores remained the same, but the intervention group VAS scores decreased in a statistically significant way (p < 0.01). Results support that such exercise reminder software programs may help to reduce perceived pain among office workers. Further long term studies with more subjects are needed to describe the effects of these programs and the mechanism under these effects. PMID- 22317656 TI - Effect of finger interaction on individual finger: index finger. AB - Grip strength is affected by such as enslaving effect, force sharing effect, and force deficit effect relating to the interaction among fingers. The author attempts to analyze index finger strength according to grip span of adjacent middle finger. 6 male graduate students participated as subjects in this experiment. The grip span has been applied from 45 mm to 60mm to investigate the effects of a coordination of grip spans on the index and middle finger strength. Results showed that index finger strength was the smallest in case of index finger grip span of 45 mm. Index finger strength decreased as the middle finger grip span. In general index finger strength shared a decreasing trend when the grip span of the middle finger increased. This study has an implication that the grip span of index and middle fingers influences force sharing effect on index finger. PMID- 22317657 TI - Psychosocial indicators among aircraft maintenance workers with and without neck and shoulder musculoskeletal symptoms. AB - In the aircraft maintenance industry, most of workers performs manual handling tasks of different materials, varying from small objects up to large pieces of the aircraft. It can increase the occurrence of work-related musculoskeletal disorders (WMSDs), which are strongly associated with high physical demands required by the task. Moreover, psychosocial demands are considered as risk factors for musculoskeletal disorders in both the upper limbs and lumbar spine. Thus, the objective of this study was to assess psychosocial indicators among aircraft maintenance workers according to the presence of neck and shoulder musculoskeletal symptoms. Eighty workers of an aircraft maintenance company were evaluated (32.69 +/- 8.25 years, 79.8 +/- 13.4 kg, 175 +/- 7 cm). According to physical examination, 50 workers were classified as asymptomatic (AS - 4.1 +/- 3.17 positive signs) whilst 30 workers were classified as symptomatic (SS - 26.72 +/- 11.44 positive signs). AS and SS have shown similar profile of demand (p = 0.62), control (p = 0.66) and social support (p = 0.74) according to the Job Content Questionnaire. However, the groups are different when considering work engagement variables. In general, SS have higher scores than AS (p < 0.05). PMID- 22317658 TI - Risk factors, clinical features and outcome of treatment of work related musculoskeletal disorders in on-site clinics among IT companies in India. AB - Workrelated musculoskeletal disorders among the IT professional is a common area of concern worldwide. This study was taken up to analyze the prevalence of risk factors, clinical features and outcome of treatment in onsite clinics in vaious information technology companies in India. Result revealed poor office ergonomics (54%), lack of keyboard tray (25%), lack of mouse tray (35%), lack of foot rest (60%), improper monitor height (80%) were the major self reported risk factors. Major identified MSD were Myofascial Pain Syndrome (49.20%), Thoracic outlet syndrome (25.02%), Fibromyalgia syndrome (8.5%). Majorly affected body regions were neck (64.9%), shoulder (42.1%), lower back (56.5%) and thigh (34.2%). The results were comparable with the literature. Feedback of the participants also revealed most of the participants were well satisfied with SHARAN's protocol. PMID- 22317659 TI - Ergonomic recommendations when texting on mobile phones. AB - The aim of this report was to give ergonomic recommendations in order to prevent musculoskeletal symptoms/disorders among young people due to intensive texting on mobile phones. In a study of 56 Swedish young adults (19-25 years, 41 with musculoskeletal symptoms in neck and/or upper extremities and 15 without symptoms) registration of thumb movements with electrogoniometry, muscle activity with electromyography and observation of texting technique were conducted during texting on mobile phones. The results showed differences in physical load between the group with musculoskeletal symptoms and the group without symptoms. There were also found differences in muscle activity and kinematics between different texting techniques. These differences could not be explained by the asymptomatic group having symptoms but may be a possible contribution to their symptoms. According to these results it can be recommended to support the forearms, to use both thumbs, to avoid sitting with the head bent forward and to avoid texting with high velocity in order to prevent musculoskeletal disorders when using mobile phones for texting. PMID- 22317660 TI - Applying a time-limit model of movement frequency to field data: is it possible? PMID- 22317661 TI - Prevalence of cervicobrachial discomforts in elementary school teachers. AB - OBJECTIVE: To determine the incidence of cervicobrachial order discomforts in Elementary Public School teachers from 1st to 4th years in the city of Pato Branco - PR. METHODS: Cross-sectional study made with 160 public school teachers from 1st to 4th years in the city of Pato Branco - PR. Data collection was made from a structured questionnaire, and a physical examination with manual palpation and orthopedic tests. RESULTS: The obtained data showed the presence of pain in the trapezius muscle region, on the left side, in 52.5%; and, on the right side, in 50.6%. The analysis also showed that there is a strong relationship between the cervicobrachial problems presented and the labor activity. The final evaluation of this study demonstrates the great need of primary care for these workers, that is, carrying out activities to prevent musculoskeletal diseases developed through work, either to preserve the individuals' physical integrity or the quality of education. CONCLUSIONS: The prevalence of musculoskeletal disorders was high among teachers. There is evidence that the prevalence was connected to job demands. PMID- 22317662 TI - Prevalence of discomfort/pain complaints and related factors in dental professionals of the public health service in Araucaria, Parana state, Brazil. AB - This poster presents a study about the influence of gender related factors, age, body weight, time of service in the profession and practice of physical exercise on the prevalence of discomfort/pain complaints in dental professionals. The scope of this study was limited to 123 subjects, 84.24% of professionals in the public dental clinics, who answered the multidimensional analytical work questionnaire. The data suggest that the lack postural awareness can contribute to the maintenance of painful conditions and also the low commitment to self-care can perpetuate the state of musculoskeletal discomfort/pain, justifying the application of the ergonomics concepts in the workplace and systematic guidance to professionals to adopt a healthy lifestyle. PMID- 22317663 TI - Exposure assessment in different occupational groups at a hospital using Quick Exposure Check (QEC) - a pilot study. AB - In order to test the feasibility and sensitivity of the ergonomic exposure assessment tool Quick Exposure Check (QEC), a pilot-study was conducted. The aim was to test QEC in different occupational groups to compare the exposure in the most common work task with the exposure in the work task perceived as the most strenuous for the neck/shoulder region, and to test intra-observer reliability. One experienced ergonomist observed 23 workers. The mean observation time was 45 minutes, waiting time and time for complementary questions included. The exposure scores varied between the different occupational groups as well as between workers within the occupational groups. Eighteen workers rated their most common work task as also being the most strenuous for the neck/shoulder region. For the remaining five workers, the mean exposure score were higher both for the neck and shoulder/arm in the most common work task. Intra-observer reliability shows agreement in 86% of the exposure interactions in the neck and in 71% in the shoulder/arm. QEC seems to fulfill the expectations of being a quick, sensible and practical exposure assessment tool that covers physical risk factors in the neck, upper extremities and low back. PMID- 22317664 TI - Musculoskeletal symptoms and work ability among agricultural machinery operators. AB - Those subjects whose employment has physical demands present more frequently musculoskeletal symptoms than others. The agricultural sector activities include tasks with important physical demands that may have a negative impact in the workers health. The aim of this study was to evaluate the presence of musculoskeletal symptoms and its association with work ability in agricultural machinery operators. It is a cross-sectional study. The participants (n = 204) answered a self-administered questionnaire on demographics, work and lifestyle characteristics, Work Ability Index and the Nordic Musculoskeletal Symptoms Questionnaire. The response rate was 89.78%. The mean age of the workers was 32.3 years, and 47.1% of them reported musculoskeletal symptoms at least one body part over the past 12 months. Those subjects who presented work ability index <37 points, 87.5% reported some kind of musculoskeletal symptom. This study showed that the work ability was significantly (p <= 0.05) correlated to musculoskeletal symptoms presence. It is recommended that measures to promote and improve the work ability are designed and deployed based on musculoskeletal disorders prevention. PMID- 22317665 TI - Musculoskeletal symptoms in workers of a Telecom Company. AB - Millions of people work with computers every day. Human work provides a means of comfort and ease to perform the tasks, favoring incorrect postures. Among the employees of a telecom company, it appears that all make use of computer, remaining in a seated position leading in musculoskeletal symptoms. METHOD: This is a quantitative study, conducted in a telecom company in the city of Curitiba. Were interviewed 27 analysts who work in engineering department, who agreed to participate and receive guidelines regarding sitting posture. This study, consisted of a structured questionnaire and the Nordic Musculoskeletal Questionnaire with musculoskeletal symptoms indicators. After answering the questionnaire, the subjects were guided through the folder on correct posture and positioning front the computer. RESULTS AND FINAL CONSIDERATIONS: Of employees 74% were male, and 100% of the employees are the computer's user, remaining in the sitting posture during working day. Concerning the break time, 74% reported that they frequently do it. Been the average working day is 8 hours. Regarding the frequency of musculoskeletal symptoms, 70% of employees reported some symptoms during the last 12 months but only one came to be sick leave. It is necessary to an analysis of the work situation, evaluating and correcting inadequacies of securities and the risks inherent in function, making prevention. PMID- 22317666 TI - Musculoskeletal symptoms and workers' perception about job factors in a pulp and paper industry. AB - The study aimed to conduct a literature review as a step of the development of a new questionnaire about the nursing workers' perception of job factors that may lead to musculoskeletal symptoms. An information synthesis was achieved by collecting data from studies that fitted the search criteria. The results showed that despite the existence of several job factors related to musculoskeletal symptoms, no specific questionnaire that evaluates this relationship was found. Therefore, this literature review presents important topics for developing the first questionnaire to analyze work activities that may contribute to pain and discomfort among nursing personnel. PMID- 22317667 TI - Physical variation in low-load work - physiological effects during exposure & recovery. AB - Trends in industry are leaning towards jobs that are more stereotyped at lower workloads. Physical variation is a potential ergonomic intervention. However, little is known of physiological response to different kinds of variation. To investigate this issue, three kinds of isometric contraction patterns with the same mean amplitude, cycle time, and duty cycle were compared. Fatigue responses were measured by multiple biomechanical and physiological approaches. In exercise, sustained and intermittent contractions with zero force had a greater number of statistically significant differences in fatigue responses. Intermittent contractions with amplitude 1/2 and 11/2 of mean force had effects intermediate but close to the sustained contraction. In recovery, sustained contractions led to decreased twitch forces 24 hours post-exercise whereas both intermittent contractions recovered within 60 minutes. This suggests that time varying forces, even without complete muscular rest, may be a useful intervention to reduce local and perceived fatigue in workers performing low-load tasks. PMID- 22317668 TI - Raising awareness of psychosocial factors in the occurrence of low back symptoms in developing countries. AB - Although there is strong evidence that single physical, psychosocial and organisational risk factors are each independent predictors of low back symptoms (LBS), little is known about their combination/interaction, particularly in those working in developing countries. A total of 1294 Indonesian coal mining industry workers reported information about physical, psychosocial, and organisational factors using self-reported questionnaires and were placed into one of four combination exposure groups: 1) high physical (working with bent trunk; whole body vibration exposure; lifting) and high psychosocial (high effort; low reward; work stress), 2) high physical and low psychosocial, 3) low physical and high psychosocial, and 4) low physical and low psychosocial (as the reference group). The odds of LBS in the high physical and high psychosocial group was 5.15 times (95% confidence interval 2.69-9.86) that of the reference group. Psychosocial factors played a more important role than physical factors in increasing the likelihood of reporting LBS. Permanent and night shift workers were more likely to report LBS. These findings imply that efforts to reduce LBS in this workplace should address both psychosocial and physical factors but psychosocial factors should be the priority, with a special focus on permanent and night shift workers. PMID- 22317669 TI - Low back injuries related to nursing professionals working conditions: a systematic review. AB - OBJECTIVE: Identify the prevalence of low back disorders and associated risks, as well as the characteristics and ergonomic factors present in the work of nursing professionals. METHODS: Systematic review based on the search of terms such as low back pain, professionals, hospital ergonomics, work organization, nursing found in national and international databases. RESULTS: The prevalence of low back pain symptoms was between 14.7% and 72% and the main cause, that is, the transference of the patient from bed to chair, leaded to the profession abandonment as a main consequence. CONCLUSION: it was possible to conclude that the prevalence of low back injury is high among nursing professionals and its causes are related to occupational factors - physical or psychological, which are in many cases permanent and disabling. PMID- 22317670 TI - Cardiovascular and subjective strain during upper limb endurance tests. PMID- 22317671 TI - Field data for "acceptable" frequency of repetitive task: data to support standardization work. PMID- 22317672 TI - Stress and musculoskeletal discomfort among hydrocarbon industry workers in Mexico. AB - This study of 114 workers in the hydrocarbon industry was conducted to identify the relationship between stress and musculoskeletal discomfort, and to view the roles played by such factors as age, schooling, obesity, workplace and job seniority. All factors except seniority were found to affect the presence of musculoskeletal discomfort in some area of the body. PMID- 22317673 TI - Analysis of the compensatory postures adopted by day caregivers through OWAS Ovako Working Posture Analysing System. AB - The Ergonomic Work Analysis reports that there are many activities performed by the professional caregivers and that they are exposed to physical and psychological overload. This situation favors the emergence of pain which influences the quality of life in the work place. In this way, the objective of this study was to verify the main postural constraints adopted by caregivers in public day cares. Visits were conducted in 28 day cares aiming at performing an interview to 126 caregivers who have been working for more than 4 years. From the questionnaire it was found that 80% of the participants refer some sort of pain, being 42% in the trunk, 33% in the shoulder and 25% in the lower limbs. The data from OWAS method showed that from the total of 30 postures performed during the work One could see that the main postures adopted by the caregivers were: flexion, lateral inclination and rotation of the trunk and most of the time they are standing. These movements, when bad performed, can lead to injuries in the lower limbs, upper limbs and trunk. It's necessary more attention to these workers.Thought preventive ergonomic actions to reduce pain symptoms and promote a work in health and safety. PMID- 22317674 TI - The physical workload analysis method : application of ergonomics standards for companies of any size. PMID- 22317675 TI - Ergonomic and organizational analysis of an association of collectors of recyclable waste. AB - The managerial difficulties encountered by an Association of Recyclable Materials Collectors to organize and ensure the perpetuation of his work gave rise to this research. In order to overcome the difficulties encountered with regard to accounting, organizational and ergonomic work, we used a methodology capable of providing a greater interaction between researchers and collectors, facilitating the exchange of knowledge and the perpetuation of the techniques used. Improvements were seen in relation to screening, storage and organization of work. PMID- 22317676 TI - Consequences of organizational commitment in abolished company sports team - a case study in Japan. AB - The purpose of this study was to show that how the abolishment of company sports team influenced the organizational commitment in employees. In this study, Three Component Model of Organizational Commitment (Meyer and Allen, 1997) was tested with 16 employees (10 males, 6 females) of T Company in NAGANO prefecture. The average age of the participants was 44, 50 years (SD=+/-0.85). And from 16 employees, 3 male employees were measured on organizational commitment with interview test. According to the analysis, the relation between organizational commitment in employees and the abolishment of company sports team was not positive significant correlation. Furthermore, results of interview test did not show the relation between organizational commitment in employees and the abolishment of company sports team. However, results of interview test showed the relation with organizational commitment of players in T Company sports team. Consequently, the goal to possess a sports team in T Company was not to boost organizational commitment in employees. In addition, it is necessary to reconsider the correlation among employees engaged in T Company in the future. PMID- 22317677 TI - A study on the relationship between commitment of club activity and vocational readiness among university students. AB - The purpose of this study was to clarify the relationship between commitment of club activities and the vocational readiness among juniors at university. In this study, organizational commitment questionnaire (Mowday, 1979) and vocational readiness scale (Wakabayashi, Goto, and Shinkai, 1983) were tested with 178 (120 men, 58 women) juniors at one physical education university in the metropolitan area. According to correlation analysis, the relation between commitment of club activities and the vocational readiness was positive significant correlation (r = .303, p < .01). Moreover, we executed t-test. As the combined results, this study provided the following three conclusions; 1) Vocational readiness score of students who belonged to the club were higher than that of other students. 2) Vocational readiness score of students who were committed to club activities were higher than that of students with low commitment to club activities. 3) Students who were committed to club activities tended to increase the score of vocational readiness. It was not able to be declared that there were positive influences of the club activities in university education from the viewpoint of vocational readiness acquisition. Therefore, it is necessary to consider what the club activities should be from the viewpoint of university student's career education. PMID- 22317678 TI - Relationship between collective efficacy and contextual performance among university athletes in Japan. AB - The purpose of this study was to clarify the relationship between collective efficacy and contextual performance among university athletes in Japan. We carried out 305 university athletes (201 males, 104 females) from 14 teams in various geographic areas in Japan. The average age of the participants was 19.91 years (SD = 1.01). The kinds of sports were soccer, basketball, baseball, volleyball, and so on. Then, using Collective Efficacy Questionnaire for Sports (CEQS; Sandra E. Short et al., 2005) and Contextual Performance Scale (Ikeda, and Furukawa, 2008), we examined the relationship between collective efficacy and Contextual performance. In conclusion, this study provided the following three remarks. 1) There are relationship between collective efficacy and contextual performance. 2) Contextual performance execution level improve collective efficacy. 3) It is important to always recommend contextual performance in own team to strengthen the collective efficacy more. PMID- 22317679 TI - A longitudinal study on the effects of team building for university baseball team in Japan: from the view point of team-vitalization. AB - The purpose of this study was to examine the effect in the experience of TB among university baseball team from the view point of team-vitalization. We carry out one university baseball team (102 males, 6 female). The average age of the participants was 19.99 years (SD = 1.41). Then, using Check List of Team- Vitalization that was developed by consulting firm in Japan, we examined the degrees of team-vitalization. The answers of this investigation were collected from the participants at fifth times (before intervention of TB, immediately after TB, after three months of TB, before intervention of follow-up training of TB, and immediately after follow-up training of TB). This study for eight months provided the following three conclusions; 1) University baseball team was vitalized through the experience of TB. 2) Team-vitalization was higher than before TB experience, but this effect of the TB did not seem to be permanent. 3) To keep intervention of TB was very important. PMID- 22317680 TI - Relationship between state anxiety and success rate in game performance, coach's evaluation among Japanese university volleyball players. AB - The purpose of this study is to examine the relationship between state anxiety and individual athletic game performance. The subjects were 54 male players of 4 teams (The average age was 20.5 (SD=1.09) years), who participated in the Kanto university men's volleyball league games in the spring of year 2010. The subjects were asked to respond to a Japanese version of the State Trait Anxiety Inventory (STAI), which was measured at 4 time periods (the day before, the day of game, just before the game, just after the game) for each of a total of 40 games (each team played 10 games). The results were as follows: (1) Relationships between state anxiety and success rate in game performance (spike, reception, block) showed different correlation depending on each game performance. (2) The group of players who performed well in games collected by coaches scored lower than the more badly-performing group in the score of state anxiety on the day of game and just after the game. (3) The temporal change of the score of state anxiety from just before the game to just after the game was different depending on whether they performed well or not in games. PMID- 22317681 TI - Construction of the integrated model for practical career support to the professional athletes. AB - Recently, along with the enhancement of the argument for career of athletes, many researchers who major in sports psychology focus mainly on athletic retirement, a coordination of transitions in sport or and outside sport, social support and professional assistance in career transition, in the context of the second career concerning to professional athletes in Japan. However, when it comes to career transition of professional athletes, it is necessary to consider "career" from the whole perspectives of human life. Therefore, the purpose of this study is to clarify the career transition of professional athletes by the way of questionnaire and interview survey, which is approached from the view point of industrial/organizational psychology. For this purpose, we implemented the interview survey to professional athletes in 2008. In addition, we carried out the investigation to professional football players (interview survey: 5 players, questionnaire survey: 102 players) in 2009. Consequently, three following findings were led in conclusion. (1)Career intervention to professional athletes should be performed before the turning point of the career (career transition). (2)It is important to assess the career intervention to professional athletes. (3)It is an important stance to watch the processes when professional athletes open up one's career by oneself. PMID- 22317682 TI - Using Balanced Scorecard (BSC) approach to improve ergonomics programs. AB - The purpose of this paper is to propose foundations for a theory of using the Balanced Scorecard (BSC) methodology to improve the strategic view of ergonomics inside the organizations. This approach may help to promote a better understanding of investing on an ergonomic program to obtain good results in quality and production, as well as health maintenance. It is explained the basics of balanced scorecard, and how ergonomists could use this to work with strategic enterprises demand. Implications of this viewpoint for the development of a new methodology for ergonomics strategy views are offered. PMID- 22317683 TI - Proposal for an integrative methodology to development the ergonomic program. AB - This paper collects the experience for both, academic and professional practice, and deal with the stages and level of involvement from different elements in the organization. The work is focused in some kind of concentric cycles, the very outside circle is formed by those that interact with ergonomic process in a year period, and the inner cycles are those that acts in a daily or weekly intervention. The success of the program still depending on the good will of the managers, but any action directed on benefit of the people at work, enable the moral as well as indicators for health and safety. PMID- 22317684 TI - Ports modernization and its influence on trade unions. AB - The restructuring of production resulting from the Port Modernization Law (Law 8.630/90) caused significant changes in work organization of Brazilian Ports. In the case of Mucuripe (Fortaleza, Ceara), in particular, the changes were very intense as Mucuripe is an old port that, before the Law, had labor regulation being governed by Trade Unions. This paper aims to present the perceptions of Union Representatives on the changes brought about by the Law on work organization in the port of Fortaleza, its influence in the organization and in the way the Unions deal with this new reality. Open and exploratory interviews were conducted with representatives of occasional labor workers registered in the Port of Fortaleza OGMO (Orgao Gestor de Mao de Obra, Labor Regulation Management). The analysis of the collected material in the interviews was based on the technique of content analysis proposed by Bardin (1979). Trade Unions have undergone a great loss of power and it has reflected in a relative inability to perform its function and to fight for the rights of the workers. The obvious Trade Unions weakness - a reduction of strikes and less unionized workers - reflects the dominating ideology of capital. PMID- 22317685 TI - The relationship between perceived quality and divulgation strategies of products in the electronic marketplace. AB - This article introduces concepts regarding management design, the electronic marketplace and recommendation systems, as well as uses a revised bibliography proposing the relationship between applied management design strategies and recommendation products identified through Cazella and the different types of perceived quality developped by Michalos and Schwartz. PMID- 22317686 TI - Cognitive and organizational ergonomics in the transition of the new integrated center of control of an oil refinery: human reliability and administration of changes. AB - The conception of a product is closely tied to its adaptation level to the users. In this view, designers are increasingly oriented to survey the needs and features of the users. This paper aims at developing a diagnosis of employees working in high-complexity activities in a petrochemical company, in light of the physical and operating changes in the Integrated Center of Control; assessing the reception sensibility to changes; assessing the cognitive pattern of the group; and making suggestions that might eliminate or minimize the difficulties in the transition process of the change, in order to reduce the adaptation period. The field of study comprised 111 production, transfer and storage operators, forming 5 groups of desktop activities. The stages of the study followed the following flow: survey of the prescribed tasks and organizational structure; Concentrated Attention test; application of the Work and Disease Risks Inventory (ITRA, Portuguese acronym); and structured psychological interview. The ITRA results pointed to a serious cognitive cost (3.83) for all five groups, this being the largest intervention focus. The items: division of task contents (3.52), social professional relationships (2.93), quality of the physical environment (2.91), physical cost (3.24), emotional cost (2.71), freedom of expression (3.77), professional fulfillment (3.41); experience and suffering (2.75), lack of recognition (2.18) and physical injuries (2.07) were considered critical. Meanwhile, social damages (1.64) and psychological injuries (1.35) are bearable. As to the Concentrated Attention test, most workers registered average level. In the individual interviews, workers showed that larger involvement in the process of physical, organizational and operational change in the desktops and on field works was required, as well as the follow up of implementations, so as to reduce the adaptation process and prevent rework (furniture, equipment, noise, form of communication with the area and training for the changes). As a result of the findings handed to the management and returned to the workers, several actions were implemented on ergonomic non-conformities found in the analysis. It is possible to prove the importance of the insertion of cognitive and organizational ergonomics in the building projects of new facilities for high-complexity activities in petrochemical plants. PMID- 22317687 TI - Mind reading through the eyes: an fMRI study. AB - Mind reading is the ability to understand another person's thoughts, intentions, and feelings (Whiten, 1991). The purpose of this study was to clarify which part of the brain is evoked while mind reading in functional Magnetic Resonance Imaging (fMRI) experiments, using a mind reading task, the Reading Mind in the Eyes Test (RME: Baron-Cohen et al., 2001) with four choices (mental state words). The participants were right-handed and sex-matched healthy Japanese university students (10 males and 10 females, age range 19-25). We used periodic ABA...block design in the fMRI sessions. Task A (an experimental task) was the mind reading task and Task B (a control task) was the age-gender task. In order to clarify the activated region of the brain while mind reading, we calculated the difference between the degrees of BOLD (Blood-oxygen-level dependent) activation during the Task A and Task B. The results showed that there was a significant difference in activation of the right superior occipital gyrus, and the left parietal lobe. These findings indicated that these regions were used while mind reading. The role of these regions was discussed in terms of the findings from previous studies. PMID- 22317688 TI - Daily rhythm of salivary IL-1beta, cortisol and melatonin in day and night workers. AB - Shiftwork-induced sleep deprivation and circadian disruption probably leads to an increase in the production of cytokines and dysregulation of innate immune system, respectively. This project aims evaluating changes in salivary IL-1 beta, cortisol, and melatonin in night workers. Method. Two day and three night healthy workers participated in this study. Sleep was evaluated by actimetry and activity protocols. Saliva was collected at waking and bedtime the last workday and the following two days-off and was analyzed by ELISA. Results. Neither sleep duration nor efficiency showed any association with salivary IL-1beta. IL-1beta levels were higher at waking than at bedtime during working days for all workers, but only one day and one night-worker maintained this pattern and hormone rhythms during days off. For this night worker, melatonin levels were shifted to daytime. A second one presented clear alterations in IL-1beta and hormone rhythms on days off. Conclusions. Our preliminary results suggest that night work can disturb the variation pattern of salivary IL-1beta. No association of this variation with sleep was observed. It seems that disruption in hormone rhythms interfere with salivary IL-1beta production. IL- 1beta production pattern seems to be maintained when rhythms are present, in spite of a shift in melatonin secretion. PMID- 22317689 TI - Association between repetitive work and occupational cold exposure. AB - Occupational cold exposure is an important risk factor that increases stress at work and can induce many health effects like diseases and symptoms related to cold, including work-related musculoskeletal disorders. The methodological procedures were performed to measure these environmental variables as recommended by the ISO 7726/85. For the analysis of repetitiveness was used the OCRA checklist and evaluation of musculoskeletal morbidity conducted by the Nordic Musculoskeletal Questionnaire. So the objective of this study was to investigate the correlation between cold environmental variables and prevalence of musculoskeletal morbidity in the repetitive work. Was found association between work in cutting and boning sector (occupational cold and repetitive work) and the presence of musculoskeletal morbidity, with a significance of 99%. PMID- 22317690 TI - An epidemiological profile of cashiers holders carpal tunnel syndrome in a grocery store chain. AB - Occupational diseases are those acquired in the work. Statistics show an increase number of cases, victims like typists, telephone's operators, cashiers and many others with varied levels of involvement. It is composed of disorders affecting the upper limbs being recognized by the Ministry of Social Welfare. Among these diseases stands out for its high occurrence Carpal Tunnel Syndrome (CTS). It has been considered a disease of the century, because its incidence has increased in 40.8% of repetitive stress disorders, with prevalence in females, and predominant age ranging from 25 to 40 years. It is characterized by pain and paresthesia in the first four fingers and wrists, and arm pain, weakness, numbness in the territory of the median nerve, preserving or not the palmar sensation and numbness in the median sensory distribution. This study aims to assess functional capacity and severity of symptoms presented by cashiers diagnosed with CTS. It is a descriptive and quantitative in nature. The population consists of 13 grocery store cashiers of both sexes, with a workload of 42 hours. We will be used as an instrument called the Boston Carpal Tunnel Questionnaire. That purports to be an effective means of measuring the numbness and pain in hands and wrists. Exclusion criteria we consider the subjects who have other diseases associated with CTS. The collection is with the possibility of partial results to be entered in a spreadsheet in Microsoft Excel for data analysis and subsequent discussion and correlation with the current literature. PMID- 22317691 TI - Economic incentives and the epidemiological indicators can contribute to the reduction of occupational hazards? AB - This article intends to discuss the interfaces of Decree No. 6042 and the adoption of its guidelines as a strategy to reduce the occupational hazards. PMID- 22317692 TI - Assessment of quality of sleep and sleepiness in workers with rotating shifts. AB - The study aims to evaluate the sleep quality and presence of daytime sleepiness in workers. PMID- 22317693 TI - Ergonomic initiatives at Inmetro: measuring occupational health and safety. AB - This work studies biomechanical hazards to which the workforce of Instituto Nacional de Metrologia, Qualidade e Tecnologia Industrial (Inmetro) is exposed. It suggests a model for ergonomic evaluation of work, based on the concepts of resilience engineering which take into consideration the institute's ability to manage risk and deal with its consequences. Methodology includes the stages of identification, inventory, analysis, and risk management. Diagnosis of the workplace uses as parameters the minimal criteria stated in Brazilian legislation. The approach has several prospectives and encompasses the points of view of public management, safety engineering, physical therapy and ergonomics oriented design. The suggested solution integrates all aspects of the problem: biological, psychological, sociological and organizational. Results obtained from a pilot Project allow to build a significant sample of Inmetro's workforce, identifying problems and validating the methodology employed as a tool to be applied to the whole institution. Finally, this work intends to draw risk maps and support goals and methods based on resiliency engineering to assess environmental and ergonomic risk management. PMID- 22317694 TI - Quality of diet of working college students. AB - Considering the scarcity of studies with young workers and the role of diet in the prevention of chronic diseases, the objective of the study was to assess the quality of diet of working college students. The present study investigated 43 university students, aged between 18 and 25 years old who had systematically being involved in a working activity in the past 6 months, paid or unpaid, at least 6 hours daily, five days a week. Dietary intake measured by seven dietary records covering every day of the week was used to calculate the Brazilian Healthy Eating Index Revised (B-HEIR). It was observed a low B-HEIR score (53.43,+/-7.81) indicating a risk of a poor quality of diet, with high intake of sodium and sugar and low consumption of fruits and whole grains. This poor quality of diet can result in an inadequate nutritional status that may increase the risk of obesity and chronic diseases. PMID- 22317695 TI - Ergonomic risks on the operational activities of firefighters from Rio de Janeiro. AB - The Fire Brigade of the State of Rio de Janeiro (CBMERJ) is Brazil's most ancient and is one of the military forces of the state. It has the primary function of activities related to civil defense of the state. This study aims to contribute to the improvement of the current situation by proposing a solution of eliminating totally or at least mitigating risks of ergonomic injury, since all operating activities are based on the performance of man, applying techniques and equipment with intensive use of hands, teamwork, extended shifts and living with stressful situations, which enhance the occurrence of awkward postures among other ergonomic risk factors. This is a quantitative study. The fields of study were five operational units with the highest statistical service of the Corporation. The following items were analyzed: profile of the firemen, work environment, activity performed, adequacy of training received and epidemiological assessment of pain. In total, 208 questionnaires were answered. Data analysis was performed by frequency and presented in tables, charts and graphs. It is important to implement procedures aimed at occupational health and safety of firefighters in the light of ergonomic concepts, so that crews activities are carried out with increased safety and quality. PMID- 22317696 TI - The ruler of inclusion in the process of people learning with visual disability. AB - The aim of this project is the development of a pedagogical tool that could address the needs related to the learning process of the blind and could also be used in the pedagogical process of people who are visually impaired. This project also has the objective of showing how the forms of the Ruler of Inclusion were planned in order to facilitate learning while addressing issues related to its safety, practicality and multifunctionality, aspects that are broached in a future work using descriptive, exploratory and phenomenological analyses to verify the understanding of the learning concepts applied to the ruler. PMID- 22317697 TI - Teachers' sick leave due to mental and behavioral disorders and return to work. AB - This manuscript presents a review of the literature about medical leaves due to mental and behavioral disorders and return to work of teachers. There are scarce published manuscripts. Most articles relate with prevalence of mental disorders and factors associated with the work organization, and did not mention intervention proposals and or changes in the work organization and teaching work. Proposed actions are discussed. PMID- 22317698 TI - Work of gravediggers and health. AB - Gravediggers have death as object of their work. Their activities are painful, physically and mental demanding, as well as unhealthy. Literature is scarce about this theme. The aim of this study is to evaluate gravediggers' work activities and health consequences. The methodological frame which guided this study was Dejours' psychic suffering and its association with the psychodynamic aspects of work. Data collection took place in April-May 2011 in one public and one private cemetery of Sao Paulo, Brazil. Four male workers, aged between 45 to 60 years old were interviewed. Their work activities were observed during a workday. Participants reported their life dreams, defense mechanisms and frustration. The discourse of gravediggers showed serious problems associated to physical and mental demands, public invisibility and/ or social devaluation of work. The most important physical symptom was body pain. In spite this is a preliminary study, it was possible to raise a number of work stressors and health outcomes of gravediggers, an "invisible" worker of our society. PMID- 22317699 TI - Cognitive representation of the comprehension test of safety warnings using multivariate methods. AB - This paper presents a multivariate method to assess the comprehension of safety signs. The proposed method uses the MDS and Procrustes, to obtain a consensus perceptual map. The results show that the map allowed discriminating signs with high levels of comprehension from others. The safety signs have no statistical difference as depicted by Bootstrap Analysis. PMID- 22317700 TI - Changes in human cervical and lumbar spine curves while bicycling with different handlebar heights. AB - Cycling is a daily activity that needs a high demand of human-bicycle fitness. However, studies into the fitness or ergonomic aspects are very little. In this study, the simulated 20 min bicycling test were performed by 26 male participants under 5 handle height conditions. Body joint angles and external cervical/lumbar spine lordosis were measured at the initial and cycling after 20 min. Results show that different handle heights did cause various trunk inclinations. Trunk inclination was negatively and positively correlated with lumbosacral angle (r = 0.620, p < 0.001) and cervical angle (r = 0.510, p < 0.001), respectively. In this study, regression models were also developed to predict the internal cervical and lumbar spine movements by external trunk inclination and head extension, respectively. The explanatory abilities for the variance of the models were 67.2% for LSA and 82.8% for CE prediction. This can be used to understand the cyclist's spine movements while field study of bicycling. PMID- 22317701 TI - Identification of the mental workload of public employees in the administrative sector at a public university. AB - In the workplace there are risk factors that can overwhelm the health of the worker causing physical and psychological disorders. Among these disorders, is occupational stress. Thus, this research proposes to measure the mental workload of job stress from the identification of demand, control and social support. It is an observational cross-sectional epidemiological character, performed with the Rectory office workers at the State University of West Parana (Unioeste). Data collection was due to the application of the "Job Stress Scale" (JSS) and in its reduced version adapted to Portuguese. The survey sample consisted of 44 individuals. Statistical analysis was correlated inversely with medium intensity (r = -0.404) between age and social support. For males was found between control and age (r = 0.603). According to the data obtained, we conclude that most workers are exposed to passive work, leading to loss of skills or disinterest in the job. This study highlights the importance of research in the area and the need for new actions that change the conditions of stress at work. PMID- 22317702 TI - What is safety culture and risk-taking like at a large steel manufacturing company? AB - Focus group interviews were conducted at a large steel manufacturing company with 1000 employees, in order to answer the research question: what is the safety culture and risk-taking like at the company, according to employees? Ten focus groups were used for data collection consisting of 6-8 employees each. The participants were operators from production. The interviews lasted 75 min and were digitally recorded and thereafter verbatim transcribed. Descriptive data was also collected from all participants by allowing them to fill out a short questionnaire. The results of this study will be presented at the conference as a poster presentation. PMID- 22317703 TI - Attention deficit/hyperactivity disorder's effects on individuals' scan paths during a simulated drive. AB - Individuals who have Attention Deficit/Hyperactivity Disorder (ADHD) experience adverse effects relating to driving; additionally, they experience deficits in scanning ability. The present study examined the effects of ADHD on eye tracking while driving. This study consisted of ten participants, of which, five have ADHD. It was hypothesized that individuals who have ADHD will make more saccadic eye movements and thus shorter fixations than individuals without ADHD (Control). Furthermore, it was hypothesized that despite the fact that individuals who have ADHD will make more saccadic eye movements than individuals without ADHD, those individuals with ADHD will commit more traffic violations including collisions compared to the control group. Findings indicated that hypothesis one was not supported by the data, whereas hypothesis two was supported in that ADHD individuals' had more collisions and committed more traffic violations than the control group. Additionally, a significant difference was found in the spatial distributions of the fixations between the ADHD and Control groups. The findings of this study could help better understand the factors involved in ADHD driving and could be used to train individuals with ADHD to become more aware of their surroundings and driving habits and thus become safer drivers. PMID- 22317704 TI - Comparison of five approaches to keeping power line maintainers' hands warm during work in the cold. AB - Electric utility workers in Canada must frequently work in the cold and must wear thick rubber gloves which can result in rapid fatigue and reduced performance. The purpose of the study was therefore to document the challenge of working in the cold wearing the standard five-finger rubber gloves and covers and compare them to two equipment options, mitten style gloves or a prototype wool liner, and two heating options, glove or torso heating. The dependent measures were grip force, temperature, dexterity (modified Purdue pegboard test and a simulated occupational task), finger sensitivity (Von Frey hair test), perceived effort and thermal sensation. The study population consisted of 10 experienced male utility workers. They worked in a controlled temperature walk-in chamber (-20 degrees Celsius) and performed simulated utility work for 45 minutes with interspersed test batteries. The mitten style glove and woolen liner in a standard glove reduced the effects of working in the cold compared to the standard five-fingered variety with a thin cotton liner. We found that the mitten style glove showed lesser drops in skin temperature for the 3rd and 5th digits than the other conditions (p < 0.05). PMID- 22317705 TI - A method to assess safety and resilience in radiopharmaceuticals production process. AB - Radiopharmaceuticals are radiation-emitting substances used in medicine for radiotherapy and imaging diagnosis. A Research Institute, located in Rio de Janeiro, produces three radiopharmaceuticals: the sodium iodate is used in the diagnosis of thyroid dysfunctions, the meta-iodo-benzylguanidine is used in the diagnosis of cardiac diseases, and the fluordesoxyglucose is used in diagnosis in cardiology, oncology, neurology and neuropsychiatry. This paper presents a method to access safety and resilience in radiopharmaceuticals production processes. The method uses resilience indicators in order to proactively evaluate and manage the safety. PMID- 22317706 TI - Screening stress factors survey in an institute of advanced studies: health and safety integrated plans. AB - The current paper presents the study of organizational stressors survey carried out in a military institute, responsible for researches of high demand on aerospace technology. The study considered the theoretical framework of Organizational Ergonomics, combined with the technical guidelines of Psychology applied to Work Safety. The participatory approach was used on daily work assessment and decision making, aiming the adoption of corrective and preventive measures, considering possible distortions and imbalances between prescribed and actual activities. Thus, it was sought to engage and encourage the participation of the Institute's workers in the reflection/creation of better solutions to daily problems and to achieve productivity, without prejudice in the occupational health and safety. PMID- 22317707 TI - Administrative rationality and coping strategies in shift work. AB - Shift work (SW) can affect worker health and productivity. Working at night, workers often accumulate fatigue and are less productive. In Brazil, laws have been drafted aiming to reduce night work and rotating shift hours. In order to slash costs, companies have been looking for new arrangements to improve productivity under these conditions. The purpose of this study was to examine management changes and their outcomes in a large glass factory located in an industrial region of Brazil. The results show that the management, seeking equal productivity among shifts, focused its efforts mainly on distributing employee expertise. The arrangement resulted in 12 different groups that combine to serve three fixed shifts. A same shift can be served by more than one group, and the members of a same group share days off on different days. There was no statistically significant productivity difference among the three shifts. The on site examination showed that part of the production was held by the workers and transferred to the next shift in order for them to be able to meet the management's performance rate requirements. The finding shows how a Brazilian cultural trait (resistance without conflict) is used to drive coping in SW. PMID- 22317708 TI - Quantitative noise analysis at two marble finishing plants in Olinda, Pernambuco, Brazil. AB - In Olinda there are an estimated 50 marble quarries, 3 of which are members of the stone extraction and finishing industry's state union. The objective here is to quantitatively evaluate the noise present at the workplace in two of Olinda's unionized marble quarries. The data to be analyzed was collected during December 2010, this month representing one of the four busiest months of production. The samples were collected from Tuesdays to Fridays in order to avoid irregular outcomes. Instantaneous readings were taken with the decibel meter to identify points of Noise Pressure Level (NPL) higher than Action Level (AL). Afterwards, the full procedure for the characterization of noise level with the decibel meter in order to compare the Homogeneous Exposure Group (HEG) to those with High Risk Exposure (HRE) was initiated. The noisiest sources came from humid cutting machines, marble saws and polishing equipment. The activities of cutter and polisher became classified as follows: unsafe, in a critical situation and in need of priority control for the work environment with noise level values varying from 95.0 dB(A) to 103.3 dB(A), calling for the use of ear protection during the entire work day. PMID- 22317709 TI - Application of preliminary risk analysis at marble finishing plants in Recife's metropolitan area. AB - The finishing of marble occurs in quarries all over Brazil, being the most significant dimension of the ornamental stone sector, with 7,000 businesses. Recife's Metropolitan Area (RMR) contains approximately 106 marble quarries, 25 of them unionized. The study focused on the application of Preliminary Risk Analysis, conducted at two unionized quarries: M1, a small business; and the second, M2, considered a micro enterprise. In this analysis both the administrative and the productive sectors were evaluated. The fieldwork was done in the month of December 2010. The study revealed that the two quarries carried moderate risks in the administrative sector, mainly due to ergonomic factors, and that in the productive sectors the risks were high, specifically because of excess noise, dust material, and precarious electrical installations. Using the results of the qualitative analysis as a base, the need for quantitative study presents itself in order to determine the most adequate modes of protection to be of assistance in the management of these risks, guaranteeing the safety and health of the worker and consequently the improvement in productivity in this sector. PMID- 22317710 TI - Pulmonary function and exercise capacity in metal industry workers. AB - This article intends to evaluate the lung function and capacity to exercise and correlate both of them in metal industry workers. PMID- 22317711 TI - Study of activities of postmen motorcyclists: a look at motorcycle accidents. AB - This article presents the steps of transforming the material and organizational aspects in the work environment, beyond the social order for the proper development of activities in the Household Distribution Center, the Postmen Motorcyclists. The demand was made by managers from the accident records, establishing the need to identify the working conditions of postmen motorcyclists, regarding motorcycle accidents occurring on public roads. METHOD: Based on the characteristics of the steps required by the methodology, was necessary to realize internal and external observations, with the aim of identifying the dynamics of the accident and the collective dimensions of activity which requires a strategy for monitoring the work on the street. PMID- 22317712 TI - Use-related risk analysis for medical devices based on improved FMEA. AB - In order to effectively analyze and control use-related risk of medical devices, quantitative methodologies must be applied. Failure Mode and Effects Analysis (FMEA) is a proactive technique for error detection and risk reduction. In this article, an improved FMEA based on Fuzzy Mathematics and Grey Relational Theory is developed to better carry out user-related risk analysis for medical devices. As an example, the analysis process using this improved FMEA method for a certain medical device (C-arm X-ray machine) is described. PMID- 22317713 TI - The profile of cyclists in the city of Juiz de Fora. AB - The problems related to the means of transport in urban Brazilians have been getting worse over the years. The increase of the fleet, to the detriment of the adequacy and extent of the road network of cities contributes to this fact. This paper presents a profile of users of cycling in the city of Juiz de Fora, and thus contributes to the study of sustainable urban mobility, providing researchers with information that can guide the search for the encouragement of the use of means of transport to meet environmental needs urban centers that contributes to social equity. PMID- 22317714 TI - In-depth analysis of road crashes involving powered two-wheelers vehicles: typical human functional failures and conditions of their production. AB - Traffic safety related to motorcycle riding constitutes a growing issue all over the world. This is notably the case in France, where the important progress recently obtained toward a safer driving by car didn't prove to be so much effective for motorcycling. The present study has the purpose to give some cues on the reasons why, by characterizing the specificities of accident scenarios involving a powered two-wheeler (PTW). It is based on an in-depth accident analysis conducted by research teams composed of a psychologist and a technician intervening on the scene of the accident and later on. A sample of 384 accident cases involving a PTW is compared to a sample of 1174 car drivers involved in an accident without PTW. The results show the important differences regarding the human errors committed by PTW riders and by car drivers. They also show the interactional aspects of these different errors in the production of accidents, in the sense the physical and behavioral characteristics of PTW lead to certain errors by car drivers (perceptive failures) and these errors lead in turn to certain errors by PTW riders (prognostic failures). PMID- 22317715 TI - Mobility and accessibility in historic cities. AB - The historic cities of Brazil, despite its colonial structure, don't fail to go through transformations that affect contemporary cities, which is the main source of problems, leading to new approaches to urban issues such as mobility and accessibility. The uncontrolled growth of tourism in the historic cities can be considered as a big problem, because at the same time, they have committed to the conservation of its built heritage and demand control of the activities that occur in their areas without harm. Then, a permanent dialogue between conservatives and planners could be accomplished by joining the various sectoral policies. The study of urban mobility in historical sites was in fact the focus of this work because of their peculiarities, such as its specific characteristics of urban structure, morphology and occupation. In fact, the development of tourism in historic centers generates specific demands, such as adaptation to new uses of the houses, intensive movement of people and vehicles, illegal parking, among others. Beyond threatening the city preservation, does not provide mobility and accessibility to tourists, because these cities were not designed for the tourism conditions and needs of contemporary life. Characteristic features of Brazilian baroque cities, such as topography , the narrow streets, narrow or nonexistent sidewalks, steep turns and ramps strong, are not suitable for heavy vehicles, traffic and pedestrian circulation. Thus, studies concerning conservation urban integrated are aimed at an approach to interaction between historic preservation of the environment with the dynamic socio-economic of the local. PMID- 22317716 TI - Distractions N' Driving: video game simulation educates young drivers on the dangers of texting while driving. AB - The proliferation of portable communication and entertainment devices has introduced new dangers to the driving environment, particularly for young and inexperienced drivers. Graduate students from George Mason University illustrate a powerful, practical, and cost-effective program that has been successful in educating these drivers on the dangers of texting while driving, which can easily be adapted and implemented in other communities. PMID- 22317717 TI - Determining skill transferability of action games as a method to reduce in vehicle phone distractions. AB - Distracted driving has been shown to be a safety issue in numerous studies. To combat this problem, in-vehicle technology, legislation, media interventions, and other methods have been proposed and attempted. However research indicates that the drivers themselves may circumvent, ignore, or not be able to react in time for these interventions to be effective. Therefore research into training programs for drivers may improve reaction time under distraction. Research indicates that action game players have faster reaction times and more attentional resources than non-players on paper-based tests. However, transferability to driving has not been studied yet. This paper outlines a study to determine if action game players perform better at a driving task based on frequency of game-play. Participants will be placed into two groups of play (high vs. low) and tested against two levels of distraction (none vs. phone conversation). It is expected that participants who play higher frequency of action games will perform better under distraction than lower frequency players. Driver performance, conversation recall, frequency and durations of eye fixations will be analyzed based on previous research which has validated those variables as a measure of distraction and higher workload. PMID- 22317718 TI - The impact of emotions and predominant emotion regulation technique on driving performance. AB - Emotion-provoking stimuli abound on modern roadways. Driving measures, of both longitudinal and lateral control of the vehicle, have been shown to vary based on affective influences. Research, however, has yet to address how drivers' individual techniques to mitigate emotional reactions influence driving performance. To address this issue, the present study featured a dual-task protocol involving simulated driving together with processing of emotionally valenced images with a focus on different Predominant Emotion Regulation Techniques (PERT): one adaptive strategy (task-focused coping) and one maladaptive style (emotion-focused coping). Dependent measures included mean driving speed and number of lane excursions. Results indicated that pleasant images degraded longitudinal control to the greatest extent, while unpleasant images produced the greatest detriment in lateral control. Additionally, individuals' PERT played a major interactive role in drivers' longitudinal control leading task-focused females and emotion-focused males to adhere more closely to the speed limit; yet, it did not affect their lateral control. Results hold important potential implications for the amount or variety of training necessary for driver licensure to promote and sustain safe vehicle control. PMID- 22317719 TI - The effects of iPod and text-messaging use on driver distraction: a bio behavioral analysis. AB - This study was designed to empirically examine the effects of iPod device and text-messaging activities on driver distraction. Sixty participants were asked to perform a driving simulation task while searching for songs using an iPod device or text messaging. Driving errors as measured by lane deviations were recorded and analyzed as a function of the distracters. Physiological measures (EEG) were also recorded during the driving phases in order to measure participant levels of cortical arousal. It was hypothesized that iPod use and text messaging would result in a profound effect on driving ability. The results showed a significant effect of iPod use and text-messaging on driving performance. Increased numbers of driving errors were recorded during the iPod and text-messaging phases than the pre- and post-allocation phases. Higher levels of Theta activity were also observed during the iPod and Text-messaging phase than the pre- and post allocation phases. Implications for in-vehicle systems design, training, and safety are also discussed. PMID- 22317720 TI - Use of color lights for the detection of anomalies in quality systems. AB - The importance of eye care in the industry is a first level topic, due to most of the assembly and manufacturing aimed companies of various products that require direct health care of their employees, specially eye care. The lighting system, the lamp features and job tasks are factors that impact over the visual performance of the worker. Each of these factors, either by themselves or in conjunction, influences the visual performance of the employee, and therefore its safety and efficacy. Some of the reported symptoms are: problem of visual fixation, eye redness, tearing, headache, blurred vision, eyelids heaviness and dry eyes, [7]. The research was developed with 48 people, 27 male and 21 female, in the range of ages of 17 to 58 years old. In the experiment were used illumination system base on Diode Emitting lights (LED's) of five different colors (White, Blue, Green, Red and Yellow), the reason of use of LED's it is because are source of monochromatic light, also it is also saving power light and low heating dissipation. PMID- 22317721 TI - Case studies--ergonomics in projects. AB - The aim of a series of sessions on Company Case Studies, is to learn from practical experiences, to give feed back to researchers on applicability of theories, methods and techniques, and last but not least, to market ergonomics. In order to learn from case material, reports need to be easy accessible and well structured. System ergonomics provides such a structure. Usually a project is not done twice, i.e. with and without ergonomics. Therefore, it is not possible to make comparisons and determine the impact of ergonomics directly. A different approach is needed. It has been suggested at the IEA2006 World Congress, to compile a database of published case studies, each case to be reported in a fixed report format and critically reviewed to enable generalizing the outcomes. This paper proposes such a format. At the IEA2012 World Congress 40 case studies have been accepted, representing applied ergonomics cases in manufacturing, process industries, aviation and logistic systems. PMID- 22317722 TI - Airport baggage handling--where do human factors fit in the challenges that airports put on a baggage system? AB - The challenges put on large baggage systems by airports can be summarized as: handling a high number of bags in a short period of time, in a limited space, with all sorts of disruptions, whilst complying with stringent regulation upon security, sustainability and health and safety. The aim of this company case study is to show in the different project phases--as indicated in the system ergonomic approach--how the human factors specialist can play a major part in tackling these challenges. By describing different projects in terms of scope, organization, human factors topics covered, phases and lessons learned, the importance of Human-Computer Interaction, automation as well as manual handling and work organization in baggage is addressed. PMID- 22317723 TI - Ergonomic work analysis of airbus pilots job in Brazil. AB - This article is the result of a case study of ergonomic work analysis carried out in a Brazilian airline company, focused on the safety of the activity of Airbus pilots from the company's national lines. The study was divided in three parts, each one with different approach. First step is how critical situations such as accidents and incidents are dealt with during flight. Then it comes to discuss about adversities found in the working place, the airbus cockpit, and the development of risk map. Last but not least, the study focused in how the irregular working journey compromises the biological clock of the pilots end may cause social issues. PMID- 22317724 TI - Transforming a hospital safety and ergonomics program: a four year journey of change. AB - The conception of "Patient Safety" being the number one priority at Hospitals can reduce the emphasis on overall employee safety and health. This review examines a hospital's need to improve 24/7 active (i.e., not reactive) coverage, regulatory compliance, as well as the frequency and severity of employee injury losses. It also discusses a journey to integrate and improve safety and ergonomics to achieve these goals. Three approaches used by the ergonomist to create the transformation included: 1) adoption of the safety and ergonomic hazard identification; 2) safe patient handling; and 3) implementation of a 5S program. The results of the four (4) year effort at the not for profit, 637 bed, full service, acute-care hospital has shown a steady decline in frequency, reduced waste, and improved housekeeping. Ergonomists can have a key role in transforming Hospital Safety and Ergonomic Programs. PMID- 22317725 TI - Integration of ergonomics in the prevention policy of a large university hospital. PMID- 22317726 TI - Return on investment of an on-site employee health clinic in multinational information technology company in India. PMID- 22317727 TI - Design and implementation of a novel tool addresses the greatest cause of wrist injuries at Bayer Healthcare. AB - Sanitary clamp wingnut manipulation is the fifth most frequent cause of injuries in the production areas of the Bayer Healthcare site in Berkeley, California. Task analysis showed that manual manipulation of clamp wingnuts had concurrent multiple risk factors, including: awkward postures, high forces, contact stresses, and high frequency. Task elimination was not an option. Several tools on the market were researched and tried but it was found that no existing tools would alleviate the associated ergonomics risk factors. An interim tool found on the market was used as a short term solution until an optimal design could be manufactured. A tool was designed, fabricated, and tested in-house at the Bayer machine shop. The tool was originally designed to fit all variations of clamp wingnuts, but then was found to fit too loosely for some. By using a comparison between inventory and cost benefit analysis it was decided to standardize the wingnuts types leaving the two most common types. A final prototype of the tool fit these two types of wingnuts. The efficient methods by which clamps were replaced and how tools were implemented in cleanroom manufacturing areas are described in this paper. This ten month project potentially eliminated all of the ergonomics risk factors associated with clamping. PMID- 22317728 TI - Ergonomics, automation and logistics: practical and effective combination of working methods, a case study of a baking company. AB - The aim of this study was to combine three different analytical methods from three different disciplines to diagnose the ergonomic conditions, manufacturing and supply chain operation of a baking company. The study explores a summary of comprehensive working methods that combines the ergonomics, automation and logistics study methods in the diagnosis of working conditions and productivity. The participatory approach of this type of study that involves the feelings and first-hand knowledge of workers of the operation are determining factors in defining points of action and ergonomic interventions, as well as defining opportunities in the automation of manufacturing and logistics, to cope with the needs of the company. The study identified an ergonomic situation (high prevalence of wrist-hand pain), and the combination of interdisciplinary techniques applied allowed to improve this condition in the company. This type of study allows a primary basis of the opportunities presented by the combination of specialized methods of different disciplines, for the definition of comprehensive action plans for the company. Additionally, it outlines opportunities for improvement and recommendations to mitigate the burden associated with occupational diseases and as an end result improve the quality of life and productivity of workers. PMID- 22317729 TI - Development of an ergonomics device for maintenance of hydraulic generators of Tucurui hydropower plant. AB - This paper aims to present an ergonomic device to assist in the maintenance of the units of Tucurui Hydropower Plant. The development of this ergonomic device made possible to reduce maintenance time, reduce losses caused by billing, improve performance and reduce the physical strain for labors during the execution of services. PMID- 22317730 TI - Design and implementation of ergonomic performance measurement system at a steel plant in India. AB - Management of Tata Steel, the largest steel making company of India in the private sector, felt the need to develop a framework to determine the levels of ergonomic performance at its different workplaces. The objectives of the study are manifold: to identify and characterize the ergonomic variables for a given worksystem with regard to work efficiency, operator safety, and working conditions, to design a comprehensive Ergonomic Performance Indicator (EPI) for quantitative determination of the ergonomic status and maturity of a given worksystem. The study team of IIT Kharagpur consists of three faculty members and the management of Tata Steel formed a team of eleven members for implementation of EPI model. In order to design and develop the EPI model with total participation and understanding of the concerned personnel of Tata Steel, a three phase action plan for the project was prepared. The project consists of three phases: preparation and data collection, detailed structuring and validation of EPI model. Identification of ergonomic performance factors, development of interaction matrix, design of assessment tool, and testing and validation of assessment tool (EPI) in varied situations are the major steps in these phases. The case study discusses in detail the EPI model and its applications. PMID- 22317731 TI - Ergonomic study of an operator's work of a molybdenum plant. AB - This study was part of an ergonomic program which is being carried out through an agreement between the University of Concepcion and a Chilean private mining company. The purpose of this case study was to identify working conditions in which the physical and mental workload could be over the capabilities of the operator. He was responsible for loading trucks with sacks of molybdenum and for downloading reagents and handles them. The methods employed in this study included electronic records, interviews, surveys, review of the company standards, a time study and physical and mental workload analysis. Results showed that 84% of the time the operator was carrying out principal and secondary activities and no break periods were detected. It was found that the pace of work and the shift system generated unfavorable conditions by imbalance in the workload on the different days of the week. In the light of the results recommendations were made for a number of ergonomic changes. Most of them were accepted by the company. The most important achievement was a change in the shift system. The overload of the operator was due to the fact that he was in a shift working 5 days and resting on weekends. The imbalance was mainly because the work of the week end was accumulated for Monday. As a result of the study, the company contracted a second worker for this job and adopted a 7x7 shift system, meaning that they work seven days and rest seven days. An evaluation carried out two month after adopting the new shift revealed that changes were well accepted by the worker. PMID- 22317732 TI - Ergonomic work analysis of urban bus drivers in Rio de Janeiro city. AB - This article is the result of a case study on ergonomic work analysis carried out in an urban bus company located in Ilha do Governador, Rio de Janeiro. The methodology used in this work follows the French-tradition Ergonomic Analysis of the Work (EWA) combined with the best tradition from anglo-saxon ergonomic work analysis. The situated diagnosis was performed to provide relevant information about the work conditions of a bus driver. PMID- 22317733 TI - Biomechanical modelling and evaluation of construction jobs for performance improvement. AB - Occupational risk factors, such as awkward posture, repetition, lack of rest, insufficient illumination and heavy workload related to construction-related MMH activities may cause musculoskeletal disorders and poor performance of the workers, ergonomic design of construction worksystems was a critical need for improving their health and safety wherein a dynamic biomechanical models were required to be empirically developed and tested at a construction site of Tata Steel, the largest steel making company of India in private sector. In this study, a comprehensive framework is proposed for biomechanical evaluation of shovelling and grinding under diverse work environments. The benefit of such an analysis lies in its usefulness in setting guidelines for designing such jobs with minimization of risks of musculoskeletal disorders (MSDs) and enhancing correct methods of carrying out the jobs leading to reduced fatigue and physical stress. Data based on direct observations and videography were collected for the shovellers and grinders over a number of workcycles. Compressive forces and moments for a number of segments and joints are computed with respect to joint flexion and extension. The results indicate that moments and compressive forces at L5/S1 link are significant for shovellers while moments at elbow and wrist are significant for grinders. PMID- 22317734 TI - Eletrobras management program in ergonomics: the pursuit of excellence through maturity levels. AB - Ergonomics for Eletrobras arose from the need in having an environment more suitable to the characteristics and circumstances of employees, in compliance with Regulation Standard no. 17 - Ergonomics (NR17) of the Ministry of Labor and Employment. Being a mixed economy company with regionalized anthropometric characteristics of its employees, the study of ergonomic adjustments and improvement of the concept of Ergonomics were and have been of great importance to the company's production environment. These advances have contributed to the development of specific technical criteria for the purchase of furniture and work tools (accessories), apart from their possible effects on the user. Ergonomics has been perceived as a technical-scientific tool, aimed to study labor interactions, new technologies and specific characteristics of the activities performed. To meet these demands a multidisciplinary Ergonomics Committee was created in Eletrobras, and effectively established the Ergonomics Management Program in the company; This program is marked by well-defined phases with great success in making use of these studies for other types of corporate activities and also facilitating the program control and its maturity levels, even at a business level. PMID- 22317735 TI - Ergonomic design of crane cabins: a case study from a steel plant in India. AB - The study, carried out at the Batch Annealing Furnace (BAF) shop of Cold Rolling Mill (CRM) at an integrated steel plant of India, concerns ergonomic evaluation and redesign of a manually-operated Electrical Overhead Travelling (EOT) crane cabin. The crane cabin is a complex worksystem consisting of the crane operator and twelve specific machine components embedded in a closed workspace. A crane operator has to perform various activities, such as loading and unloading of coils, setting and removal of convector plates, and routine maintenance work. Initially, an operator had to work in standing posture with bent back most of the time. Ergonomically poor design of the chair and the controls, awkward work postures, and insufficient vision angle resulting in musculoskeletal disorders (MSDs) are some of the critical problems observed.. The study, conceived as an industry-academia joint initiative, was undertaken by a design team, the members of which were drawn from both the company concerned and the institute. With the project executed successfully, a number of lessons, such as how to minimize the anthropometric mismatch, how to improve the layout of the components and controls within enclosed workspace, and how to improve work posture minimizing risk of MSDs have been learned. PMID- 22317736 TI - 3M Brazil ergonomics: a success story in the making. AB - The aim of this project is to present two case studies and provide job assessment results, share implemented solutions, and provide information about realized cost and benefits. In this session, two cases studies, one from Sao Jose do Rio Preto and the other from Sumare, will be presented. These projects won AEIA awards in 2009 and 2010, respectively. The projects describe the application of the Ergonomic Risk Reduction Program, which both improves worker's quality of life and productivity and product quality as well. PMID- 22317737 TI - Ergonomics and design: its principles applied in the industry. AB - Industrial Design encompasses both product development and optimization of production process. In this sense, Ergonomics plays a fundamental role, because its principles, methods and techniques can help operators to carry out their tasks most successfully. A case study carried out in an industry shows that the interaction among Design, Production Engineering and Materials Engineering departments may improve some aspects concerned security, comfort, efficiency and performance. In this process, Ergonomics had shown to be of essential importance to strategic decision making to the improvement of production section. PMID- 22317738 TI - A case study of smoke detector assembly work method intervention and evaluation. AB - The study aimed to evaluate a work method intervention in a smoke detector assembly line. High hand gripping forces and extreme wrist postures were found in the smoke detector assembly line at UTC Fire & Security Company in Maine. A fixture was introduced to replace the old assembly method. Electromyography (EMG) and electrogoniometry were used to measure the workers' hand gripping force and wrist motions with both the old and new assembly methods. Results show both hand gripping forces and wrist postures improved significantly with the new method. PMID- 22317739 TI - Participatory ergonomic intervention for prevention of low back pain: assembly line redesign case. AB - This paper gives an overview of a participatory ergonomic intervention aimed at reducing low back pain cases in the dispatch department of a catalogue and e commerce retail company. Based on the findings of the ergonomic analysis and design committee, the company's own employees redesigned the assembly line's layout. As a result of these changes two job tasks that involved manual material handling of boxes, identified by the revised NIOSH equation as posing an increased risk for lifting-related low back pain, were totally eliminated, and the employees responsible for moving boxes from the end of the assembly line to pallets on the ground were given more control over their jobs, and these jobs were also enriched with a new, less heavy task. These results demonstrate that participatory ergonomic interventions are a viable and effective strategy to reduce the exposure to work-related physical and psychosocial risk factors for low back pain. PMID- 22317740 TI - How to use programme theory to evaluate the effectiveness of schemes designed to improve the work environment in small businesses. AB - Due to the many constraints that small businesses (SBs) face in meeting legislative requirements, occupational health and safety (OHS) regulatory authorities and other OSH actors have developed programmes which can reach out to SBs and motivate and assist them in improving the work environment. A number of conceptual models help to enhance our understanding of OHS interventions in SBs and their effectiveness. However, they have mainly been evaluated on output rather than the process relating to the change theory underlying the intervention, and hence have seldom been rigorously evaluated. Thus little is known about how particular features of SBs can be taken into account when designing and implementing national programmes. This paper shows how realist analysis and programme theory may be used as a framework for evaluating, developing and improving national intervention programmes for the improvement of the work environment and reducing injuries in SBs. It illustrates this for a specific New Zealand intervention: the Workplace Safety Discount scheme and its implementation in the agriculture sector. In practice, realist analysis should be performed during the planning, implementation and management stages so that ongoing findings can be fed back to the participant social actors to help them make appropriate changes to enhance the likelihood of success. PMID- 22317741 TI - Development of a score for assessing severity, predicting interventions and prognosis of musculoskeletal disorders. AB - Musculoskeletal disorders (MSD's) are a constellation of disorders. There is no single tool available which guides the clinicians to predict the severity, intervention and recovery period of the patients who is suffering from different musculoskeletal disorder. In this paper authors tried to categorize the severity of the musculoskeletal discomfort and the prognosis of the recovery period. The questionnaire was formulated using different epidemiological risk factor of the development of MSD and the effect of MSD on physical and psychosocial factors. The questionnaire contains 13 questions which include seven direct (rating was 0, 2, 4, 6, 8 and 10) and six indirect (rating was 0, 1, 2, 3, 4 and 5) questions. Results revealed a significant correlation with the prognosis of recovery and the actual recovery period (r= 0.80). It also showed a significant correlation between the total severity score and the actual recovery (r=0.82) period. Depending on the prognosis of the recovery the severity score was segregated in four categories as mild, moderate, severe and complicated. Due to small sample size the prognosis of recovery for higher severity score could not be plotted. PMID- 22317742 TI - Ergonomic aspects simulation digital online: an educational game proposal to promote environmental education. AB - This article addresses the ergonomic criteria that guide the construction of an educational game called Environmental Simulator. The focus is on environment navigation considering aspects of content architecture and its esthetics functionality. PMID- 22317743 TI - Immune responses to low back pain risk factors. AB - $?underline{Objective}$: Investigate effects of interactions between biomechanical, psychosocial and individual risk factors on the body's immune inflammatory responses. $?underline{Background}$: Current theories for low back pain causation do not fully account for the body's response to tissue loading and tissue trauma. $?underline{Methods}$: Two groups possessing a preference for the sensor or intuitor personality trait performed repetitive lifting combined with high or low mental workload on separate occasions. Spinal loading was assessed using an EMG-assisted subject-specific biomechanical model and immune markers were collected before and after exposure. $?underline{Results}$: Mental workload was associated with a small decrease in AP shear. Both conditions were characterized by a regulated time-dependent immune response making use of markers of inflammation, tissue trauma and muscle damage. Intuitors' creatine kinase levels were increased following low mental workload compared to that observed in Sensors with the opposite trend occurring for high mental workload. $?underline{Conclusions}$: A temporally regulated immune response to lifting combined with mental workload exists. This response is influenced by personality and mental workload. PMID- 22317744 TI - Proceedings for the 18th Triennial International Ergonomics Association's (IEA) congress: designing a sustainable future. PMID- 22317745 TI - The neural correlates of passively viewed sequences of true and false beliefs. AB - The ability to infer other people's mental states such as desires, emotions, intentions and beliefs is essential for successful social interactions, and it is usually referred to as theory of mind (ToM). In particular, the ability to detect and understand that people have beliefs about reality that may be false is considered an important hallmark of ToM. This experiment reports on the results of 18 participants who viewed photographic sequences of an actress performing actions as a consequence of true and false beliefs. Consistent with prior work, results from the passive viewing of stimuli depicting true belief indicated an increased response over frontal, central and parietal regions when compared with the amplitude for the false belief condition. These results show that (i) frontal activity is required for processing false belief tasks and (ii) parietal effects reported in previous studies to reflect specific cognitive process of monitoring others' beliefs can be elicited in the absence of an explicit instruction for mentalizing. PMID- 22317746 TI - Ab initio prediction of pressure-induced structural phase transition of superconducting FeSe. AB - External pressure driven phase transitions of FeSe are predicted using ab initio calculations. The calculations reveal that alpha-FeSe makes transitions to NiAs type, MnP-type, and CsCl-type FeSe. Transitions from NiAs-type to MnP-type and CsCl-type FeSe are also predicted. MnP-type FeSe is also found to be able to transform to CsCl-type FeSe, which is easier from alpha-FeSe than the transition to MnP-type FeSe, but comparable to the transition from NiAs-type FeSe. The calculated electronic structures show that all phases of FeSe are metallic, but the ionic interaction between Fe-Se bonds becomes stronger and the covalent interaction becomes weaker when the structural phase transition occurs from alpha FeSe to the other phases of FeSe. The experimentally observed decrease in T(c) of superconducting alpha-FeSe at high pressure may be due to a structural/magnetic instability, which exists at high pressure. The results suggest an increase of the T(c) of alpha-FeSe if such phase transitions are frustrated by suitable methods. PMID- 22317748 TI - In vivo effects of leptin on lymphocyte subpopulations in mice. AB - Leptin, a hormone-cytokine mainly produced by the adipose tissue, has pleitropic effects on many biological system including metabolic, endocrine, and immune system. Although it is well known that leptin controls food intake on hypothalamic regions of brain, the role of leptin in hematopoietic and immune processes has been mainly investigated with in vitro and transgenic mouse studies. The aim of this study was to investigate the effects of peripheral leptin on lymphocyte subpopulation. Initially forty male Swiss albino mice were divided into five groups. Mice in group I (Control) were given serum physiologic (SP) and group L100, group L250, group L500, and group L1000 were given 100, 250, 500 and 1000 MUg/kg/day recombinant mouse leptin, respectively. Leptin or SP was injected subcutaneously for the next 6 days. Daily food/water intake was recorded for each group. At the end of the study, whole blood samples (500 MUl) were obtained via intracardiac punction in anesthetized mice. Leptin levels and lymphocyte subpopulations in blood samples were analyzed. We show that no in vivo dose-dependent effect of leptin is existed on lymphocyte subpopulations count in mice. Treatment of mice with high-dose leptin led to increase only CD4+ cells (P<0.05). In addition, high-dose leptin slightly increased CD3+ cells but this was not statistically confirmed (P=0.08). Notably, it was found that leptin caused insignificant changes on body weight and food intake in normal body weight mice. The data support that high-dose leptin has proliferative effect on CD4+ cells in vivo. However, more in vivo study needs to be examined to clarify how leptin affect lymphocyte subpopulations. PMID- 22317749 TI - Engagement of heterogeneous nuclear ribonucleoprotein M with listeriolysin O induces type I interferon expression and restricts Listeria monocytogenes growth in host cells. AB - Listeriolysin O (LLO) is a key virulence factor secreted by the Gram-positive, facultative intracellular pathogen Listeria monocytogenes (LM). Its role in host cell response is still not very clear. Using pull-down assay, mass spectrometry analysis and immunoprecipitation approaches, we found that LLO interacted with heterogeneous nuclear ribonucleoprotein M (hnRNPM), a member of RNA splicing complex apparatus, and the binding domain of LLO for hnRNP M was located between amino acids 26 and 176. Knockdown of hnRNP M inhibited LLO-induced activation of IFN-alpha, IFN-beta and AP-1 promoters and enhanced LM growth in host cells. Thus, engagement of hnRNP M with LLO induces type I interferon expression and restricts LM growth in host cells, suggesting a critical role of hnRNP M in LLO induced immune responses in host cells. These findings will contribute to further understandings of the molecular mechanisms underlying the host defense against LM infection. PMID- 22317750 TI - Increased immunosuppressive function of CD4(+)CD25(+)Foxp3(+)GITR+ T regulatory cells from NFATc2((-/-)) mice controls allergen-induced experimental asthma. AB - The expansion of effector T cells is tightly controlled by transcription factors like nuclear factor of activated T cells (NFAT) family members that mediate early intracellular responses to T cell receptor-mediated signals. In this study we show that, after allergen challenge, NFATc2((-/-)) mice had augmented number of functionally intact CD4(+)CD25(++)GITR(++) T regulatory (T regs) cells in the lung. Anti-GITR antibody treatment inhibited T regulatory cell function and enhanced the number of activated lung CD4(+) T cells associated with increased IL 2 and pSTAT-5 in the airways of NFATc2((-/-)) mice in experimental allergic asthma. This agonistic treatment led to increased inflammation in the lung of NFATc2((-/-)) treated mice. These data indicate that NFATc2((-/-)) mice have increased number of CD4(+)CD25(+)Foxp3(+) T regulatory cells with induced immunosuppressive function that control allergen-induced experimental asthma. PMID- 22317751 TI - Endoplasmic reticulum chaperone glucose regulated protein 170-Pokemon complexes elicit a robust antitumor immune response in vivo. AB - Previous evidence suggested that the stress protein grp170 can function as a highly efficient molecular chaperone, binding to large protein substrates and acting as a potent vaccine against specific tumors when purified from the same tumor. In addition, Pokemon can be found in almost all malignant tumor cells and is regarded to be a promising candidate for the treatment of tumors. However, the potential of the grp170-Pokemon chaperone complex has not been well described. In the present study, the natural chaperone complex between grp170 and the Pokemon was formed by heat shock, and its immunogenicity was detected by ELISPOT and (51)Cr-release assays in vitro and by tumor bearing models in vivo. Our results demonstrated that the grp170-Pokemon chaperone complex could elicit T cell responses as determined by ELISPOT and (51)Cr-release assays. In addition, immunized C57BL/6 mice were challenged with subcutaneous (s.c.) injection of Lewis cancer cells to induce primary tumors. Treatment of mice with the grp170 Pokemon chaperone complex also significantly inhibited tumor growth and prolonged the life span of tumor-bearing mice. Our results indicated that the grp170 Pokemon chaperone complex might represent a powerful approach to tumor immunotherapy and have significant potential for clinical application. PMID- 22317752 TI - Modulation of cytokine gene expression by cathelicidin BMAP-28 in LPS-stimulated and -unstimulated macrophages. AB - Apart from direct bacterial killing, antimicrobial host defence peptides (HDPs) exert various other biological activities that also include modulation of immune responses to infection. The bovine cathelicidin BMAP-28 has been extensively studied with regard to its direct antibacterial activity while little is known about its effects on immune cell function. We have investigated its ability to affect inflammatory pathways and to influence the proinflammatory response induced by LPS in RAW 264.7 macrophages, in terms of modulation of TLR4 activation and cytokine gene induction. BMAP-28 on its own elicited ERK1/2, p38 and NF-kappaB activation leading to upregulation of IL-1beta gene expression in these cells, suggesting it has the capacity to activate selected cellular pathways through direct effects on macrophages. As expected based on its in vitro LPS-binding properties, BMAP-28 blocked LPS-induced cytokine gene expression when added to the cell culture in combination with LPS. However it enhanced the induction of IL-1beta and IL-6 genes and suppressed that of IFN-beta when added prior to or following LPS stimulation over a 30-60 min time interval, or when co administered with taxol as another TLR4 stimulant. It did not inhibit the expression of IFN-beta induced by the TLR3 ligand poly(I:C). Overall these results, and the fact that BMAP-28 increased the LPS-stimulated activation of NF kappaB while diminishing that of IRF-3, suggest that the peptide potentiates the early TLR4-mediated proinflammatory cytokine response while inhibiting the TLR4/TRAM/TRIF signaling pathway leading to IRF-3 activation and IFN-beta gene expression. Using a TLR4-specific antibody we also found that BMAP-28 decreased the LPS-induced internalization of surface TLR4 required for initiating the TRAM/TRIF signaling pathway, which provides a mechanism for the inhibitory effect of the peptide on the TLR4/TRAM/TRIF pathway. PMID- 22317753 TI - Grief and trauma intervention for children after disaster: exploring coping skills versus trauma narration. AB - This study evaluated the differential effects of the Grief and Trauma Intervention (GTI) with coping skills and trauma narrative processing (CN) and coping skills only (C). Seventy African American children (6-12 years old) were randomly assigned to GTI-CN or GTI-C. Both treatments consisted of a manualized 11-session intervention and a parent meeting. Measures of trauma exposure, posttraumatic stress symptoms, depression, traumatic grief, global distress, social support, and parent reported behavioral problems were administered at pre, post, 3 and 12 months post intervention. In general, children in both treatment groups demonstrated significant improvements in distress related symptoms and social support, which, with the exception of externalizing symptoms for GTI-C, were maintained up to 12 months post intervention. Results suggest that building coping skills without the structured trauma narrative may be a viable intervention to achieve symptom relief in children experiencing trauma-related distress. However, it may be that highly distressed children experience more symptom relief with coping skills plus narrative processing than with coping skills alone. More research on the differential effects of coping skills and trauma narration on child distress and adaptive functioning outcomes is needed. PMID- 22317754 TI - Does internet-based prevention reduce the risk of relapse for anorexia nervosa? AB - Technological advancements allow new approaches to psychotherapy via electronic media. The eating disorder literature currently contains no studies on internet intervention in anorexia nervosa (AN). This study presents a RCT on an internet based relapse prevention program (RP) over nine months after inpatient treatment for AN. The sample comprised 258 women, randomized to the RP or treatment as usual (TAU). Expert- and self-ratings were evaluated by intent-to-treat analyses. Concerning age, age at onset and comorbidity, both groups were comparable at randomization. During the RP, the intervention group gained weight while the TAU group had minimal weight loss. RP completers gained significantly more body weight than patients in the TAU condition. Group-by-time comparisons for eating related cognitions and behaviors and general psychopathology showed a significantly more favorable course in the RP program for "sexual anxieties" and "bulimic symptoms" (interview), and "maturity fears" and "social insecurity" (EDI 2). General psychopathology showed no significant group-by-time interaction. Important factors for successful relapse prevention were adherence to the intervention protocol and increased spontaneity. Considering the unfavorable course and chronicity of anorexia nervosa (AN), internet-based relapse prevention in AN following inpatient treatment appears a promising approach. Future internet based programs may be further improved and enhanced. PMID- 22317755 TI - Changes in natural language use as an indicator of psychotherapeutic change in personality disorders. AB - Word use has been shown to reflect various psychological processes and psychological change. This study examines the self-view in personality disorders (PDs) and its change over the course of therapy using the Linguistic Inquiry and Word Count analysis procedure. A sample of 299 participants with PDs and 108 community control participants wrote short essays about their lives. Patients repeated the assignment three times over two years and completed assessments of PD-pathology, general psychopathology, PD-beliefs, and quality of life. Results show that as hypothesized the use of words in the 1st Person Singular Pronouns, Negative Emotion, Causation, Past and Future Tense Verbs categories significantly declines over the course of treatment, while the use of Present Tense Verbs and Positive Emotion increases. These categories tend to distinguish patients from non-patients prior to treatment. We also found 12 additional word categories changing over time, including Word Count and Negations. Change in word use statistically predicts better treatment outcome on all outcome measures (p < .001). Reductions in the use of Negative Emotion Words and Negations are the strongest predictors of outcome. The non-hypothesized role of Negations was explored and seemed to reflect that PD-patients miss a lot in their lives. Reduction of what they miss seems central to recovery. This issue seems relatively neglected in theoretical and treatment models of PDs. An increased focus on what patients miss in their lives might improve our understanding and treatment of PDs. In sum, Negative Emotion and Negation word categories appear to reflect key treatment targets. PMID- 22317756 TI - Vitamin D3 and the risk of CVD in overweight and obese women: a randomised controlled trial. AB - Evidence indicates that vitamin D deficiency contributes to CVD. We investigated the effect of vitamin D3 supplementation on cardiovascular risk factors in women. Healthy premenopausal overweight and obese women (n 77; mean age 38 (sd 8.1) years) were randomly allocated to the vitamin D (25 MUg/d as cholecalciferol) or the placebo group in a double-blind manner for 12 weeks. Blood pressure, serum lipoproteins, apolipoproteins and anthropometric parameters were recorded. Dietary intake was recorded using 24 h food recall and FFQ. Physical activity was assessed by the International Physical Activity Questionnaire. Mean total cholesterol concentrations increased in the vitamin D group (0.08 (sd 0.56) mmol/l) but declined in the placebo group (0.47 (sd 0.58) mmol/l), and a significant effect was observed (P <= 0.001). In the vitamin D group, mean HDL cholesterol concentration increased, whereas it decreased in the placebo group (0.07 (sd 0.2) v. - 0.03 (sd 0.2) mmol/l; P = 0.037). Mean apoA-I concentration increased in the vitamin D group, although it decreased in the placebo group (0.04 (sd 0.39) v. - 0.25 (sd 0.2) g/l; P <= 0.001). Mean LDL-cholesterol:apoB 100 ratio augmented in the vitamin D group, while this ratio declined in the placebo group (0.11 (sd 0.6) v. - 0.19 (sd 0.3); P = 0.014). Body fat mass was significantly decreased in the vitamin D group more than the placebo group ( - 2.7 (sd 2) v. - 0.4 (sd 2) kg; P <= 0.001). The findings showed that supplementation with vitamin D3 can significantly improve HDL-cholesterol, apoA-I concentrations and LDL-cholesterol:apoB-100 ratio, which remained significant in the multivariate model including anthropometric, dietary and physical activity measures. PMID- 22317757 TI - Human DNA polymerase lambda catalyzes lesion bypass across benzo[a]pyrene-derived DNA adduct during base excision repair. AB - The combined action of oxidative stress and genotoxic polycyclic aromatic hydrocarbons derivatives can lead to cluster-type DNA damage that includes both a modified nucleotide and a bulky lesion. As an example, we investigated the possibility of repair of an AP site located opposite a minor groove-positioned (+)-trans-BPDE-dG or a base-displaced intercalated (+)-cis-BPDE-dG adduct (BP lesion) by a BER system. Oligonucleotides with single uracil residues in certain positions were annealed with complementary oligonucleotides bearing either a cis- or trans-BP adduct. The resulting DNA duplexes contained dU either directly opposite the modified dG or shifted to adjacent 5' (-1) or 3' (+1) positions. Digestion with uracil DNA glycosylase was utilized to generate AP sites which were then hydrolyzed by APE1, and the resulting gaps were processed by DNA polymerase beta (Polbeta) or lambda (Pollambda). The AP sites in position -1 can be repaired effectively using APE1 and Polbeta or Pollambda. The AP sites opposite the BP lesions can be repaired using Pollambda in the case of cis- but not the trans-isomeric adduct. The AP sites in position +1 are the most difficult to repair. In the case of the AP site located in position +1, the activity of Pollambda does not depend on the stereoisomeric properties of the BP lesions and dCTP is the preferred inserted substrate in both cases. The capability of Pollambda to introduce the correct dNTP opposite the cis-BP-dG adduct in gap filling reactions suggests that this polymerase may play a specialized role in the process of repair of these kinds of lesions. PMID- 22317758 TI - Metastatic lymph node ratio as an important prognostic factor in pancreatic ductal adenocarcinoma. AB - BACKGROUND: Overall five year survival following pancreaticoduodenectomy for ductal adenocarcinoma is poor with typical reported rates in the literature of 8 27%. The aim of this study was to identify the histological variables best able to predict long-term survival in these patients. METHODS: A prospective database of patients undergoing pancreaticoduodenectomy between April 2002 and June 2009 was analysed to identify patients with histologically proven pancreatic ductal adenocarcinoma. Patients with ampullary tumours, cholangiocarcinoma, duodenal adenocarcinoma and neuroendocrine tumours were excluded. The histology reports for these patients were reviewed. Uni-variate and multi-variate survival analysis was performed to identify variables useful in predicting long-term outcome. RESULTS: 134 patients underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma during this period. 5 year survival in this series was 18.6%. Uni variate analysis identified nodal status and the metastatic to resected lymph node ratio as predictors of survival. Using multi-variate Cox Regression analysis a metastatic to lymph node ratio of >15% (p < 0.01) and the presence of perineural invasion (p < 0.05) were identified as independent predictors of patient survival. Metastatic to resected lymph node ratio is better able to stratify prognosis than nodal status alone with 5 year survival of those with N0 disease being 55.6% and 12.9% for N1 disease. However for those with <15% of resected nodes positive, 5 year survival was 21.7% and in those with >15% nodes positive it was 5.2% (p = 0.0017). CONCLUSION: The metastatic to resected lymph node ratio can provide significant prognostic information in those patients with node positive disease after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. PMID- 22317759 TI - Preoperative high-sensitivity C-reactive protein predicts depression in patients undergoing coronary artery bypass surgery: a single-center prospective observational study. AB - OBJECTIVE: Our objective was to reveal the contribution of preoperative high sensitivity C-reactive protein (hsCRP) levels to the risk of depression in patients undergoing coronary artery bypass grafting (CABG). METHODS: In this study, 232 consecutive patients undergoing elective CABG were evaluated for depression utilizing the 9-item Patient Health Questionnaire scale at least 3 days before surgery and 6 months after CABG. In addition, peripheral blood samples were collected at baseline and the circulation levels of hsCRP were measured. RESULTS: The preoperative and postoperative rate of depression was 18.1%. Interestingly, preoperative depression was independently associated with women (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.13-5.50) and log transformed hsCRP (OR, 1.16; 95% CI, 1.06-1.27) after adjusting for various factors using logistic regression, including age, sex, and university-level education. Postoperative depression was only associated with log-transformed hsCRP (OR, 1.15; 95% CI, 1.05-1.25) in these patients. Log-transformed hsCRP remained associated with future depression after adjusting for postoperative medications or major adverse cardiovascular events during the follow-up period. CONCLUSIONS: The present study is the first to report elevated serum hsCRP is an independent predictor for depression in CABG patients not only preoperatively but also up to 6 months after surgery. These clinical findings may reveal a potential target for improving prognosis in CABG patients with depression. PMID- 22317760 TI - Two sides of the same coin: EGFR exon 19 deletions and insertions in lung cancer. AB - Most lung adenocarcinoma-associated EGF receptor (EGFR) mutations confer sensitivity to specific EGFR tyrosine kinase inhibitors. The finding that exon 19 insertion mutations are also sensitive to this class of drugs suggests that testing for these mutations should be done and that these patients will benefit from treatment with tyrosine kinase inhibitors. PMID- 22317761 TI - Imaging tumor sensitivity to a bioreductive prodrug: two for the price of one! AB - Hypoxia is an important characteristic of many solid tumors and has a major negative effect on treatment response. A way to combat this effect is with drugs called "bioreductive prodrugs" or "hypoxic cytotoxins," which are metabolized under hypoxia to toxic species. However, the patients with hypoxic tumors need to be identified. PMID- 22317762 TI - Statistical issues and recommendations for noninferiority trials in oncology: a systematic review. AB - To provide an overview of noninferiority trials in oncology with a special emphasis on methodologic issues, we conducted a systematic review of randomized trials assessing noninferiority of antineoplastic treatments. We identified 72 articles, of which 65 were randomized phase III trials with a single control arm, 3 were factorial phase III trials, and 4 were randomized phase II trials. Forty six were trials in lung, colorectal, or breast cancer. The quality of reporting was improved chronologically (P < 0.01); the major deficiencies were claims of noninferiority when the results did not meet statistical criteria for noninferiority (7 articles) or when the noninferiority margin was not prespecified (5 articles). Four trials (6%) presented plans for switching from superiority to noninferiority. The analysis populations were intent to treat (ITT) in 52, per-protocol set (PPS) in 6, and both ITT and PPS in 11 trials. Noninferiority margins were set in 68 trials (94%); 1 trial used both of the conventional and effect retention methods, 17 trials used the conventional method, 5 trials used the effect retention method, and in 45 trials, the method was not specified. Some trials used margins that possibly were larger than the assured effects of the active controls. No trials explicitly took into consideration uncertainty in historical data. Two trials (3%) specified 2 values of margins. Our findings highlight critical deficiencies in design and reporting of noninferiority trials. Seven practical recommendations are presented. PMID- 22317763 TI - Met kinase inhibitor E7050 reverses three different mechanisms of hepatocyte growth factor-induced tyrosine kinase inhibitor resistance in EGFR mutant lung cancer. AB - PURPOSE: Hepatocyte growth factor (HGF) induces resistance to reversible and irreversible epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR TKI) in EGFR mutant lung cancer cells by activating Met and the downstream phosphoinositide 3-kinase (PI3K)/Akt pathway. Moreover, continuous exposure to HGF accelerates the emergence of EGFR-TKI-resistant clones. We assayed whether a new Met kinase inhibitor, E7050, which is currently being evaluated in clinical trials, could overcome these three mechanisms of resistance to EGFR-TKIs. EXPERIMENTAL DESIGN: The effects of E7050 on HGF-induced resistance to reversible (gefitinib), irreversible (BIBW2992), and mutant-selective (WZ4002) EGFR-TKIs were determined using the EGFR mutant human lung cancer cell lines PC-9 and HCC827 with an exon 19 deletion and H1975 with an T790M secondary mutation. PC-9 cells were mixed with HGF-producing fibroblasts, MRC-5 cells, and subcutaneously inoculated into severe combined immunodeficient mice, and the therapeutic effects of E7050 plus gefitinib were assayed. RESULTS: E7050 circumvented resistance to all of the reversible, irreversible, and mutant-selective EGFR-TKIs induced by exogenous and/or endogenous HGF in EGFR mutant lung cancer cell lines, by blocking the Met/Gab1/PI3K/Akt pathway in vitro. E7050 also prevented the emergence of gefitinib-resistant HCC827 cells induced by continuous exposure to HGF. In the in vivo model, E7050 plus gefitinib resulted in marked regression of tumor growth associated with inhibition of Akt phosphorylation in cancer cells. CONCLUSIONS: A new Met kinase inhibitor, E7050, reverses the three HGF-induced mechanisms of gefitinib resistance, suggesting that E7050 may overcome HGF induced resistance to gefitinib and next-generation EGFR-TKIs. PMID- 22317764 TI - Frequency of driver mutations in lung adenocarcinoma from female never-smokers varies with histologic subtypes and age at diagnosis. AB - PURPOSE: Our previous study revealed that 90% [47 of 52; 95% confidence interval (CI), 0.79-0.96] of Chinese never-smokers with lung adenocarcinoma harbor known oncogenic driver mutations in just four genes EGFR, ALK, HER2, and KRAS. Here, we examined the status of known driver mutations specifically in female never smokers with lung adenocarcinoma. EXPERIMENTAL DESIGN: Tumors were genotyped for mutations in EGFR, KRAS, ALK, HER2, and BRAF. Data on age, stage, tumor differentiation, histologic subtypes, and molecular alterations were recorded from 349 resected lung adenocarcinomas from female never-smokers. We further compared the clinicopathologic parameters according to mutational status of these genes. RESULTS: Two hundred and sixty-six (76.2%) tumors harbored EGFR mutations, 16 (4.6%) HER2 mutations, 15 (4.3%) EML4-ALK fusions, seven (2.0%) KRAS mutations, and two (0.6%) BRAF mutations. In univariate analysis, patients harboring EGFR mutations were significantly older (P < 0.001), whereas patients harboring HER2 mutations were significantly younger (P = 0.036). Higher prevalence of KRAS (P = 0.028) and HER2 (P = 0.021) mutations was found in invasive mucinous adenocarcinoma (IMA). The frequency of EGFR mutations was positively correlated with acinar predominant tumors (P = 0.002). Multivariate analysis revealed that older age at diagnosis (P = 0.013) and acinar predominant subtype (P = 0.005) were independent predictors of EGFR mutations. Independent predictors of HER2 mutations included younger age (P = 0.030) and IMA (P = 0.017). IMA (P = 0.006) and poor differentiation (P = 0.028) were independently associated with KRAS mutations. CONCLUSIONS: The frequency of driver mutations in never-smoking female lung adenocarcinoma varies with histologic subtypes and age at diagnosis. These data have implications for both clinical trial design and therapeutic strategies. PMID- 22317765 TI - Is there a correlation between OSAS duration/severity and carotid intima-media thickness? AB - BACKGROUND: Obstructive Sleep Apnea Syndrome (OSAS) is a common airways disease recognized as an independent cardiovascular risk factor. It is often associated with obesity, diabetes and dyslipidemia. Its pathophysiological consequences (hypoxia, hypercapnia, micro-arousals, sympathetic hyperactivity, oxidative stress, systemic inflammation and hyper-coagulability) are implicated in the development of hypertension, endothelial dysfunction and higher intima-media thickness (IMT) values, all elements known to lead to atherosclerosis. The study aim was to demonstrate a relationship between OSAS duration and IMT values and to confirm how OSAS severity could influence IMT (a marker of atherosclerosis). METHODS: We enrolled 156 patients (125 men, mean age: 60 +/- 12 years) affected by OSAS of different severity: 111 (71%) were in CPAP therapy; some of the population were also affected by hypertension [102 (65%)], dyslipidemia [52 (33%)] and diabetes [38 (24%)]. Patients underwent evaluation of carotid artery IMT and answered a questionnaire investigating the time of onset (confirmed by a person aware of the patient's previous sleeping habits) and the duration of the disease. RESULTS: We found a statistically significant higher IMT value in patients with longer-lasting disease (OSAS duration in IMT < 0.9 mm: 120 (60-192) months versus OSAS duration in IMT >= 0.9 mm: 200 (120-310) months; p < 0.001). OSAS severity is positively related to IMT values. We found a positive relationship between IMT and OSAS duration [r = 0.34; p < 0.001] and between AHI and IMT [r = 0.51; p < 0.001]. CONCLUSIONS: Our study shows that the duration of OSAS and its severity are important factor related with higher values of IMT and hence with a higher risk of atherosclerosis. PMID- 22317766 TI - The sequential use of endocrine treatment for advanced breast cancer: where are we? AB - BACKGROUND: Hormone receptor-positive advanced breast cancer is an increasing health burden. Although endocrine therapies are recognised as the most beneficial treatments for patients with hormone receptor-positive advanced breast cancer, the optimal sequence of these agents is currently undetermined. METHODS: We reviewed the available data on randomised controlled trials (RCTs) of endocrine therapies in this treatment setting with particular focus on RCTs reported over the last 15 years that were designed based on power calculations on primary end points. RESULTS: In this paper, data are reviewed in postmenopausal patients for the use of tamoxifen, aromatase inhibitors and fulvestrant. We also consider the available data on endocrine crossover studies and endocrine therapy in combination with chemotherapy or growth factor therapies. Treatment options for premenopausal patients and those with estrogen receptor-/human epidermal growth factor receptor 2-positive tumours are also evaluated. CONCLUSION: We present the level of evidence available for each endocrine agent based on its efficacy in advanced breast cancer and a diagram of possible treatment pathways. PMID- 22317767 TI - Polymorphisms in the IL-13 and IL-4R genes are associated with the development of renal cell carcinoma. AB - BACKGROUND: Cytokines are the important modulators that bind to their relevant receptors in response to some stimuli to mediate the homeostasis. It has been suggested that the imbalance of immune system of the host might affect the generation of diseases, including cancers. PATIENTS AND METHODS: We investigated the association between six functional polymorphisms of IL-4, IL-13, and IL-4R genes and susceptibility to renal cell cancer in a hospital-based study, including 620 renal cell carcinoma (RCC) patients and 623 controls. Logistic regression model was used to assess the genetic effects on the development of RCC. RESULTS: Overall, individuals with IL-4R Ile50Val CT/TT genotypes had a 0.34 fold significantly decreased RCC risk (CT/TT versus CC), and the T variant allele was associated with a decreased risk of RCC in a dose-response manner (Ptrend=0.009). In addition, we also observed that IL-13 C-1055T and Arg130Gln polymorphisms could decrease the risk of RCC [TT versus CC/CT: odds ratio=0.36, 95% confidence interval (CI)=0.16-0.78; AA versus GG/GA: 0.66, 0.44-0.97, respectively]. Furthermore, a multiplicative interaction association between the combined IL-4R Ile50Val and IL-13 C-1055T genotypes was observed to decrease the risk of RCC (P=0.036). CONCLUSION: IL-13 and IL-4R may play an important role in the etiology of RCC. PMID- 22317768 TI - High-quality care for all children with cancer. AB - BACKGROUND: Providing high-quality care for children with cancer could improve treatment outcomes, survival and quality of life of the children and parents. The aim of this study is to select high-quality care recommendations for all children with cancer based on literature and consensus for future development of quality indicators. MATERIALS AND METHODS: We performed an extensive search in databases for scientific literature and in websites of international health care and guideline development organizations to create an inventory of recommendations for the care for all children with cancer. The RAND modified Delphi method was used to grade and select recommendations for high-quality care. RESULTS: Our search resulted in a list of 131 recommendations on care for all children with cancer. The expert panel graded, discussed and prioritized these recommendations. Analysis of these ratings resulted ultimately in a list of 109 high-quality care recommendations for all children with cancer, including 31 prioritized recommendations. CONCLUSIONS: This study defines a set of high-quality care recommendations based on literature and consensus. These recommendations provide a basis for the development of a comprehensive set of quality indicators to evaluate care in paediatric oncology. PMID- 22317769 TI - A phase II clinical trial of sunitinib following hepatic transarterial embolization for metastatic neuroendocrine tumors. AB - BACKGROUND: The liver is the predominant site of metastases among patients with advanced neuroendocrine tumors (NETs). Prior retrospective studies have reported high response rates in patients treated with transarterial embolization (TAE). NETs are highly vascular and are known to express vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR). We hypothesized that administration of sunitinib, a VEGFR inhibitor, following TAE would extend progression-free survival (PFS). PATIENTS AND METHODS: Patients with metastatic NETs to the liver underwent a series of selective TAEs followed by sunitinib (until disease progression or maximum of 12 months). Radiographic response (by RECIST), survival, and safety parameters were monitored. RESULTS: Thirty-nine patients were enrolled. The overall response rate was 72% [95% confidence interval (CI), 0.58-0.86]. Median PFS was 15.2 months. Rates of overall survival (OS) at 1 and 4 years were 95% (95% CI, 0.88-1.00) and 59% (95% CI, 0.38-0.80), respectively. A significant 34% rise in serum VEGF was observed following the initial TAE (P = 0.03). CONCLUSIONS: Hepatic TAE is a highly active treatment option for patients with metastatic NETs to the liver. Embolization stimulates release of VEGF into the circulation. Sunitinib, an oral VEGFR inhibitor, can be safely administered following embolization. The high rates of PFS and OS associated with this sequence of therapies are encouraging. PMID- 22317770 TI - High STEAP1 expression is associated with improved outcome of Ewing's sarcoma patients. AB - BACKGROUND: Ewing's sarcoma (ES) is the second most common bone or soft-tissue sarcoma in childhood and adolescence and features a high propensity to metastasize. The six-transmembrane epithelial antigen of the prostate 1 (STEAP1) is a membrane-bound mesenchymal stem cell marker highly expressed in ES. Here, we investigated the role of STEAP1 as an immunohistological marker for outcome prediction in patients with ES. PATIENTS AND METHODS: Membranous STEAP1 immunoreactivity was analyzed using immunohistochemistry in 114 primary pre chemotherapy ES of patients diagnosed from 1983 to 2010 and compared with clinical parameters and patient outcome. Median follow-up was 3.85 years (range 0.43-17.51). RESULTS: A total of 62.3% of the ES samples displayed detectable STEAP1 expression with predominant localization of the protein at the plasma membrane. High membranous STEAP1 immunoreactivity was found in 53.5%, which correlated with better overall survival (P=0.021). Accordingly, no or low membranous STEAP1 expression was identified as an independent risk factor in multivariate analysis (hazard ratio 2.65, P=0.036). CONCLUSION: High membranous STEAP1 expression predicts improved outcome and may help to define a specific subgroup of ES patients, who might benefit from adapted therapy regimens. PMID- 22317771 TI - Proteins involved in DNA damage response pathways and survival of stage I non small-cell lung cancer patients. AB - BACKGROUND: Biological complexity leads to significant variation in the survival of patients with stage I non-small-cell lung cancer (NSCLC). DNA damage response (DDR) pathways play a critical role in maintaining genomic stability and in the progression of NSCLC. Therefore, the development of a prognostic biomarker focusing on DDR pathways is an intriguing issue. PATIENTS AND METHODS: Expression of several proteins (ATM, ATMpS1981, gammaH2AX, 53BP1, 53BP1pS25, Chk2, Chk2pT68, MDC1, MDC1pS964, BRCA1pS1423, and ERCC1) and overall survival were investigated in 889 pathological stage I NSCLC patients. RESULTS: Low expression of BRCA1pS1423 or ERCC1 was significantly associated with worse survival in the whole cohort of patients. Analysis performed based on histology revealed that low expression of gammaH2AX, Chk2pT68, or ERCC1 was a poor prognostic factor in squamous cell carcinoma patients [adjusted hazard ratio (aHR), Cox P: 1.544, 0.012 for gammaH2AX; 1.624, 0.010 for Chk2pT68; 1.569, 0.011 for ERCC1]. The analysis of the interaction between two proteins showed that this effect was more pronounced in squamous cell carcinoma patients. However, these effects were not detected in adenocarcinoma patients. CONCLUSIONS: The proteins involved in DDR pathways exhibited differential expression between squamous cell carcinoma and adenocarcinoma and were important determinants of survival in stage I squamous cell carcinoma patients. PMID- 22317772 TI - Ethical requirements and authorship: not much room for interpretation. PMID- 22317773 TI - The relief of pain in labour and the role of remifentanil. PMID- 22317774 TI - Supplemental oxygen reduces serotonin levels in plasma and platelets during colorectal surgery and reduces postoperative nausea and vomiting: Retraction. PMID- 22317777 TI - Rare CNVs and tag SNPs at 15q11.2 are associated with schizophrenia in the Han Chinese population. AB - BACKGROUND: Rare copy number variations (CNVs) were involved in the etiology of neuropsychiatric disorders, and some of them appeared to be shared risk factors for several different diseases. One of those promising loci is the CNV at 15q11.2, including 4 genes, TUBGCP5, CYFIP1, NIPA2, and NIPA1. Several studies showed that microdeletions at this locus were significant associated with schizophrenia. In the current study, we investigated the role of both rare CNVs and common single nucleotide polymorphisms (SNPs) at 15q11.2 in schizophrenia in the Chinese Han population. METHODS: We screened deletions at 15q11.2 in 2058 schizophrenia patients and 3275 normal controls in Chinese Han population by Affymetrix 500K/6.0 SNP arrays and SYBR green real-time polymerase chain reaction and then validated deletions by multiplex ligation-dependent probe amplification and Taqman real-time assays. We successfully genotyped 27 tag SNPs in total and tested associations in 1144 schizophrenia cases and 1144 normal controls. RESULTS: We found a triple increase of deletions in cases over controls, with OR=4.45 (95% CI=1.36-14.60) and P=.014. In the analysis of common SNPs, we found that the most significant SNP in schizophrenia was rs4778334 (OR=.72, 95% CI=0.60 0.87, allelic P=.0056 after permutation, genotypic P=.015 after permutation). We also found SNP rs1009153 in CYFIP1 was associated with schizophrenia (OR=0.82, 95% CI=0.73-0.93, allelic P=.044 after permutation). CONCLUSION: We found that both rare deletions and common variants at 15q11.2 were associated with schizophrenia in the Chinese Han population. PMID- 22317781 TI - The practice of consanguineous marriage in Oman: prevalence, trends and determinants. AB - The practice of consanguineous marriage has been the culturally preferred form of marriage in most Arab and the Middle Eastern countries, including Oman, but due to a paucity of population-based data in the past there is a dearth of information about its form and dynamics in Oman. Recent national-level surveys allow this gap to be filled. This paper examines the prevalence, trends and determinants of consanguineous marriages in Oman using data from the 2000 Oman National Health Survey. The results indicate a very high prevalence of consanguineous marriage in Oman, as more than half (52%) of marriages are consanguineous. First cousin unions are the most common type of consanguineous unions, constituting 39% of all marriages and 75% of all consanguineous marriages. The study observed various patterns of consanguinity, some of them common with other Arab nations, and some unique in nature. Women's age at marriage, employment, place of childhood residence and geographical region appear to be significant determinants of consanguineous marriages. Consanguineous marriage shows a strong association with marital stability, early age at marriage and early-age childbearing. There has been no appreciable change in the prevalence of consanguineous unions in Oman over the last four decades despite massive socioeconomic development and modernization. However, recent marriage cohorts show slight declining trends. The results suggest that consanguinity is likely to remain stable in the future or decline at a slow rate. Specific health education and genetic counselling should be followed in line with WHO recommendations to minimize the negative health consequences of consanguinity for child health. PMID- 22317782 TI - Equations-of-motion method for triplet excitation operators in graphene. AB - The particle-hole continuum in the Dirac sea of graphene has a unique window underneath, which in principle leaves room for bound state formation in the triplet particle-hole channel (Baskaran and Jafari 2002 Phys. Rev. Lett. 89 016402). In this work, we construct appropriate triplet particle-hole operators and, using a repulsive Hubbard-type effective interaction, we employ equations of motion to derive approximate eigenvalue equations for such triplet operators. While the secular equation for the spin density fluctuations gives rise to an equation which is second order in the strength of the short range interaction, the explicit construction of the triplet operators obtained here shows that, in terms of these operators, the second-order equation can be factorized to two first-order equations, one of which gives rise to a solution below the particle hole continuum of Dirac electrons in undoped graphene. PMID- 22317783 TI - Induction of protective immune response in mice by a DNA vaccine encoding Trypanosoma evansi beta tubulin gene. AB - Surra, caused by Trypanosoma evansi, is an economically important veterinary disease of the tropics. Lack of effective drugs or vaccines have made surra a severe economic burden particularly in Asia and sub-Saharan Africa. In this study, a naked DNA construct encoding full length T. evansi beta (beta) tubulin gene was used to immunize mice, to elicit a T. evansi beta tubulin protein specific humoral immune response, delineated by ELISA. The serum cytokine profile post immunization, as determined by flow cytometry bead based assay, showed a predominant T helper cell Type 1 (Th1) response with significant increase in levels of IFNgamma and TNFalpha. Lethal challenge with T. evansi blood-form trypomastigotes post immunization generated a beta tubulin specific recall response and a stronger Th1 type serum cytokine profile which correlated with an extended survival and better control of parasitemia in the immunized mice. PMID- 22317784 TI - BQP35 is a novel member of the intrinsically unstructured protein (IUP) family which is a potential antigen for the sero-diagnosis of Babesia sp. BQ1 (Lintan) infection. AB - A new gene of Babesia sp. BQ1 (Lintan) (BQP35) was cloned by screening a merozoite cDNA expression library with infected sheep serum and using rapid amplification of cDNA ends (RACE). The nucleotide sequence of the cDNA was 1140bp with an open reading frame (ORF) of 936bp encoding a 35-kDa predicted polypeptide with 311 amino acid residues. Comparison of BQP35 cDNA and genomic DNA sequences showed that BQP35 does not possess an intron. Recombinant BQP35 (rBQP35), expressed in a prokaryotic expression system, showed abnormally slow migration on SDS-PAGE. Gel shifting, amino acid sequence and in silico disorder region prediction indicated that BQP35 protein has characteristics of intrinsically unstructured proteins (IUPs). This is the first description of such proteins in the Babesia genus. BQP35 induced antibodies production as early as one week after Babesia sp. BQ1 (Lintan) infection in sheep. No cross-reaction was observed with sera from sheep infected with other ovine piroplasms dominant in China, except with Babesia sp. Tianzhu. The interest of BQP35 as a diagnostic antigen is discussed. PMID- 22317785 TI - Transcriptomic response of Arabidopsis thaliana after 24 h incubation with the biocontrol fungus Trichoderma harzianum. AB - Trichoderma harzianum is a fungus used as biocontrol agent using its antagonistic abilities against phytopathogenic fungi, although it has also direct effects on plants, increasing or accelerating their growth and resistance to diseases and the tolerance to abiotic stresses. We analyzed Arabidopsis thaliana gene expression changes after 24 h of incubation in the presence of T. harzianum T34 using the Affymetrix GeneChip Arabidopsis ATH1. Because this microarray contains more than 22,500 probe sets representing approximately 24,000 genes, we were able to construct a global picture of the molecular physiology of the plant at 24 h of T. harzianum-Arabidopsis interaction. We identified several differentially expressed genes that are involved in plant responses to stress, regulation of transcription, signal transduction or plant metabolism. Our data support the hypothesis that salicylic acid- and jasmonic acid-related genes were down regulated in A. thaliana after 24 h of incubation in the presence of T. harzianum T34, while several genes related to abiotic stress responses were up-regulated. These systemic changes elicited by T. harzianum in Arabidopsis are discussed. PMID- 22317786 TI - Development and metabolism of the fruit and seed of the Japanese plum Ozark premier (Rosaceae). AB - The growth characteristics of some plums and their component parts have been previously studied, as have some aspects of their developmental anatomy and composition. However, little is known about either their metabolism or about the interactions between the metabolism of their component parts. In this study we investigated these aspects in the Japanese plum Ozark Premier. Throughout fruit and seed development, changes in sugar and organic acid contents, protein composition and abundance of selected enzymes were determined. In the stone, there was a transient accumulation of vegetative storage proteins. These were subsequently mobilized and this coincided with the onset of the lignification of the stone and the start of storage protein accumulation in the seed. Ribulose-1,5 bisphosphate carboxylase/oxygenase (Rubisco) was present in the seeds, even though they lacked chlorophyll, and its presence may be related to limited gas exchange. In the flesh of some fruits, phosphoenolpyruvate carboxykinase (PEPCK) and NADP malic enzyme (NADP-ME) are thought to function in the dissimilation of malate and/or citrate during ripening. However, PEPCK and NADP-ME were present in plum flesh for most of its development, although there was no net dissimilation of malate until the latter stages of ripening. There is an interaction between the developing seed and endocarp with respect to the utilization of imported sugars and amino acids. An hypothesis is presented to account for the presence of PEPCK and NADP-ME enzyme in plum flesh when there was no net dissimilation of organic acids. PMID- 22317787 TI - Exogenous proline and trehalose promote recovery of rice seedlings from salt stress and differentially modulate antioxidant enzymes and expression of related genes. AB - Proline (Pro) and Trehalose (Tre) function as compatible solutes and are upregulated in plants under abiotic stress. They play an osmoprotective role in physiological responses, enabling the plants to better tolerate the adverse effects of abiotic stress. We investigated the effect of exogenous Pro and Tre (10 mM) in seedlings of Thai aromatic rice (cv. KDML105; salt-sensitive) during salt stress and subsequent recovery. Salt stress (S, NaCl) resulted in growth reduction, increase in the Na(+)/K(+) ratio, increase in Pro level and up regulation of Pro synthesis genes (pyrroline-5-carboxylatesynthetase, P5CS; pyrroline-5-carboxylate reductase, P5CR) as well as accumulation of hydrogen peroxide (H(2)O(2)), increased activity of antioxidative enzymes (superoxide dismutase, SOD; peroxidase, POX; ascorbate peroxidase, APX; catalase, CAT) and transcript up-regulation of genes encoding antioxidant enzymes (Cu/ZnSOD, MnSOD, CytAPX, CatC). Under salt stress, exogenous Pro (PS; Pro+NaCl) reduced the Na(+)/K(+) ratio, further increased endogenous Pro and transcript levels of P5CS and P5CR, but decreased the activity of the four antioxidant enzymes. The transcription of genes encoding several antioxidant enzymes was upregulated. Exogenous Tre (TS; Tre+NaCl) also reduced the Na(+)/K(+) ratio and strongly decreased endogenous Pro. Transcription of P5CS and P5CR was upregulated, the activities of SOD and POX decreased, the activity of APX increased and the transcription of all antioxidant enzyme genes upregulated. Although exogenous osmoprotectants did not alleviate growth inhibition during salt stress, they exhibited a pronounced beneficial effect during recovery period showing higher percentage of growth recovery in PS (162.38%) and TS (98.43%) compared with S (3.68%). During recovery, plants treated with PS showed a much greater reduction in endogenous Pro than NaCl-treated (S) or Tre-treated plants (TS). Increase in CAT activity was most related to significant reduction in H(2)O(2), particularly in the case of PS-treated plants. Advantageous effects of Pro were also associated with increase in APX activity during recovery. PMID- 22317788 TI - Validation and application of a liquid chromatography-tandem mass spectrometric method for the determination of G-856 (Cur-61414) in human plasma using semi automated solid phase extraction. AB - A liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of G-856 in human plasma to support clinical development. The method consisted of a solid phase extraction for sample preparation and LC-MS/MS analysis in the positive ion mode using TurboIonSpray for analysis. d8-G-856 was used as the internal standard. A linear regression (weighted 1/concentration2) was used to fit calibration curves over the concentration range of 5.00-2000 pg/mL for G-856. There were no significant endogenous interference components in the multiple lots of blank human plasma tested. The accuracy (%Acc) at the lower limit of quantitation (LLOQ) was 98.2% with a precision (%CV) of 5.38%. For quality control samples at 15.0, 800, and 1600 pg/mL, the inter-day %CV was <= 5.03%. Inter-day %Acc ranged from 96.9 to 99.3%. G-856 was stable in human plasma for 184 days at -20 degrees C and -70 degrees C storage. G-856 was stable in human plasma at room temperature for up to 16 h and through four freeze/thaw cycles. This validated LC-MS/MS method for determination of G-856 was used to support Phase 1 clinical studies. PMID- 22317789 TI - Development and validation of LC-MS/MS methods for the determination of mirabegron and its metabolites in human plasma and their application to a clinical pharmacokinetic study. AB - Mirabegron is being developed for the treatment of overactive bladder. To support the development of mirabegron, including pharmacokinetic studies, liquid chromatography/tandem mass spectrometry methods for mirabegron and eight metabolites (M5, M8, M11-M16) were developed and validated for heparinized human plasma containing sodium fluoride. Four separate bioanalytical methods were developed for the analysis of: (1) mirabegron; (2) M5 and M16; (3) M8; and (4) M11-M15. Either solid-phase extraction or liquid-liquid extraction was used to extract the analytes of interest from matrix constituents. For mirabegron, an Inertsil C8-3 analytical column was used and detection was performed using a triple-quad mass spectrometer equipped with an atmospheric pressure chemical ionization interface. For the metabolite assays, chromatographic separation was performed through a Phenomenex Synergi Fusion-RP C18 analytical column and detection was performed using a triple-quad mass spectrometer equipped with a Heated Electrospray Ionization interface. The validation results demonstrated that the developed liquid chromatography/tandem mass spectrometry methods were precise, accurate, and selective for the determination of mirabegron and its metabolites in human plasma. All methods were successfully applied in evaluating the pharmacokinetic parameters of mirabegron and metabolites in human plasma. PMID- 22317790 TI - Long-term monitoring of fish farms: application of Nematode/Copepod index to oligotrophic conditions. AB - Interannual variability (2003-2008) of meiofaunal assemblages were analyzed in sediments beneath fish cages (Impact group) and in areas not affected by aquaculture activities (Control group). Organisms responded with spatial and seasonal variation in meiofauna assemblages, with an abrupt increase of abundances in locations beneath fish cages throughout the study period. This increase was greater during the last sampling year (2008) and mainly due to high abundances of nematodes. Univariate analyses showed differences between control and impacted sites at both sites, however, only significant variations were found in Los Gigantes, which are consistent with seasonal meiofauna variations throughout the study period. These results are partially explained by differences in current velocity between both sampling areas. The Ne/Co index showed the same trend and it seems to be a reliable index in sediment slightly affected by aquaculture wastes. This index is especially recommended in oligotrophic areas (e.g. Canary Islands) where meiofaunal assemblages are poorly represented in terms of abundances. PMID- 22317791 TI - Water quality assessment using satellite-derived chlorophyll-a within the European directives, in the southeastern Bay of Biscay. AB - The implementation of water quality European Directives requires an intensification of water quality monitoring, within the limits of the Exclusive Economic Zone. Remote sensing technologies can provide a valuable tool for frequent, synoptic, water-quality observations, over large areas. The aim of this study is to assess the ecological status of Basque coastal water bodies using satellite imagery from MODIS sensor, together with optical and chlorophyll-ain situ measurements. Thus, sea surface satellite-derived chl-a algorithms, the OC3 M, OC5 and a Local empirical algorithm, were compared against in situ measurements using satellite in situ match-ups, 90th Percentile (P90) monthly values for the 2005-2010 period. The OC5 algorithm corresponded most accurately with in situ measurements performed in the area, hence, it was selected. A P90 chlorophyll-a map was created with this algorithm to apply the classification scheme required by the directives. The classification of water bodies, based upon satellite-derived chlorophyll-a, could improve considerably the assessment of water quality. PMID- 22317792 TI - Indicators of sediment and biotic mercury contamination in a southern New England estuary. AB - Total mercury (Hg) and methylmercury (MeHg) were analyzed in near surface sediments (0-2 cm) and biota (zooplankton, macro-invertebrates, finfish) collected from Narragansett Bay (Rhode Island/Massachusetts, USA) and adjacent embayments and tidal rivers. Spatial patterns in sediment contamination were governed by the high affinity of Hg for total organic carbon (TOC). Sediment MeHg and percent MeHg were also inversely related to summer bottom water dissolved oxygen (DO) concentrations, presumably due to the increased activity of methylating bacteria. For biota, Hg accumulation was influenced by inter-specific habitat preferences and trophic structure, and sediments with high TOC and percent silt-clay composition limited mercury bioavailability. Moreover, hypoxic bottom water limited Hg bioaccumulation, which is possibly mediated by a reduction in biotic foraging, and thus, dietary uptake of mercury. Finally, most biota demonstrated a significant positive relationship between tissue and TOC normalized sediment Hg, but relationships were much weaker or absent for sediment MeHg. These results have important implications for the utility of estuarine biota as subjects for mercury monitoring programs. PMID- 22317793 TI - 210Po and 210Pb variations in fish species from the Aegean Sea and the contribution of 210Po to the radiation dose. AB - In recent years, there has been increasing interest in the significance of natural radionuclides, particularly (210)Po, in the marine environment. (210)Po, a naturally occurring alpha emitter, accumulates in marine organisms and reflects differences in their diets. In the literature, there is no data for (210)Po and (210)Pb activity concentrations for fish species on the Turkish coast of Aegean Sea. Therefore, in this study, multiple fish species were collected from six stations seasonally on the Turkish coast of Aegean Sea and were analyzed for their (210)Po and (210)Pb content. The (210)Po and (210)Pb concentrations in the fish samples were found to vary from undetectable levels to 499 +/- 44 Bq kg(-1) dry weight (dw) and from 1.0 +/- 0.3 Bq kg(-1) to 35 +/- 4.0 Bq kg(-1) (dw), respectively. There were no significant differences in the activity concentrations of (210)Po and (210)Pb in fish samples between seasons (ANOVA, P>0.05). The highest dose contribution of (210)Po to humans was calculated to be 10,530 MUSv year(-1). PMID- 22317795 TI - Performance evaluation of an anaerobic/aerobic landfill-based digester using yard waste for energy and compost production. AB - The objective of this study was to evaluate a new alternative for yard waste management by constructing, operating and monitoring a landfill-based two-stage batch digester (anaerobic/aerobic) with the recovery of energy and compost. The system was initially operated under anaerobic conditions for 366 days, after which the yard waste was aerated for an additional 191 days. Off gas generated from the aerobic stage was treated by biofilters. Net energy recovery was 84.3MWh, or 46kWh per million metric tons of wet waste (as received), and the biochemical methane potential of the treated waste decreased by 83% during the two-stage operation. The average removal efficiencies of volatile organic compounds and non-methane organic compounds in the biofilters were 96-99% and 68 99%, respectively. PMID- 22317796 TI - Nanosilver impact on methanogenesis and biogas production from municipal solid waste. AB - Silver nanoparticles (AgNPs, nanosilver) released from industrial activities and consumer products may be disposed directly or indirectly in sanitary landfills. To determine the impact of AgNPs on anaerobic digestion of landfill waste, municipal solid waste (MSW) was loaded in identical landfill bioreactors (9L volume each) and exposed to AgNPs (average particle size=21nm) at the final concentrations of 0, 1, and 10mgAg/kg solids. The landfill anaerobic digestion was carried out for more than 250 days, during which time the cumulative biogas production was recorded automatically and the chemical property changes of leachates were analyzed. There were no significant differences in the cumulative biogas volume or gas production rate between the groups of control and 1mgAg/kg. However, landfill solids exposed to AgNPs at 10mg/kg resulted in the reduced biogas production, the accumulation of volatile fatty acids (including acetic acid), and the prolonged period of low leachate pH (between 5 and 6). Quantitative PCR results after day 100 indicated that the total copy numbers of 16S rRNA gene of methanogens in the groups of control and 1mgAgNPs/kg were 1.97+/ 0.21*10(7) and 0.90+/-0.03*10(7), respectively. These numbers were significantly reduced to 5.79+/-2.83*10(5)(copies/mL) in the bioreactor treated with 10mgAgNPs/kg. The results suggest that AgNPs at the concentration of 1mg/kg solids have minimal impact on landfill anaerobic digestion, but a concentration at 10mg/kg or higher inhibit methanogenesis and biogas production from MSW. PMID- 22317794 TI - Antibacterial and physical properties of calcium-phosphate and calcium-fluoride nanocomposites with chlorhexidine. AB - OBJECTIVES: Previous studies have developed calcium phosphate and fluoride releasing composites. Other studies have incorporated chlorhexidine (CHX) particles into dental composites. However, CHX has not been incorporated in calcium phosphate and fluoride composites. The objectives of this study were to develop nanocomposites containing amorphous calcium phosphate (ACP) or calcium fluoride (CaF(2)) nanoparticles and CHX particles, and investigate Streptococcus mutans biofilm formation and lactic acid production for the first time. METHODS: Chlorhexidine was frozen via liquid nitrogen and ground to obtain a particle size of 0.62 MUm. Four nanocomposites were fabricated with fillers of: nano ACP; nano ACP+10% CHX; nano CaF(2); nano CaF(2)+10% CHX. Three commercial materials were tested as controls: a resin-modified glass ionomer, and two composites. S. mutans live/dead assay, colony-forming unit (CFU) counts, biofilm metabolic activity, and lactic acid were measured. RESULTS: Adding CHX fillers to ACP and CaF(2) nanocomposites greatly increased their antimicrobial capability. ACP and CaF(2) nanocomposites with CHX that were inoculated with S. mutans had a growth medium pH>6.5 after 3 d, while the control commercial composites had a cariogenic pH of 4.2. Nanocomposites with CHX reduced the biofilm metabolic activity by 10-20 folds and reduced the acid production, compared to the controls. CFU on nanocomposites with CHX were three orders of magnitude less than that on commercial composite. Mechanical properties of nanocomposites with CHX matched a commercial composite without fluoride. SIGNIFICANCE: The novel calcium phosphate and fluoride nanocomposites could be rendered antibacterial with CHX to greatly reduce biofilm formation, acid production, CFU and metabolic activity. The antimicrobial and remineralizing nanocomposites with good mechanical properties may be promising for a wide range of tooth restorations with anti-caries capabilities. PMID- 22317797 TI - Biomechanical testing of suture-based meniscal repair devices containing ultrahigh-molecular-weight polyethylene suture: update 2011. AB - PURPOSE: To evaluate the biomechanical characteristics of recently introduced ultrahigh-molecular-weight polyethylene suture-based, self-adjusting meniscal repair devices. METHODS: Updating a prior study published in 2009, we made vertical longitudinal cuts 3 mm from the periphery in fresh-frozen adult human menisci to simulate a bucket-handle meniscus tear. Each tear was then repaired by a single repair technique in 10 meniscus specimens. Group 1 menisci were repaired with a vertical mattress suture of No. 2-0 Ethibond (Ethicon, Somerville, NJ). Group 2 menisci were repaired with a vertical mattress suture of No. 2-0 OrthoCord (DePuy Mitek, Raynham, MA). Group 3 menisci were repaired with a single OmniSpan device with No. 2-0 OrthoCord suture (DePuy Mitek). Group 4 menisci were repaired with a single Meniscal Cinch device with No. 2-0 FiberWire suture (Arthrex, Naples, FL). Group 5 menisci were repaired with a single MaxFire device inserted with the MarXmen gun (Biomet Sports Medicine, Warsaw, IN). Group 6 menisci were repaired with a Sequent device with No. 0 Hi-Fi suture (ConMed Linvatec, Largo, FL) in a "V" suture configuration. Group 7 menisci were repaired with a single FasT-Fix 360 device (Smith & Nephew Endoscopy, Andover, MA). By use of a mechanical testing machine, all samples were preloaded at 5 N and cycled 200 times between 5 and 50 N. Those specimens that survived were destructively tested at 5 mm/min. Endpoints included maximum load, displacement, stiffness, and failure mode. RESULTS: Mean failure loads were as follows: Ethibond suture, 73 N; OrthoCord suture, 88 N; OmniSpan, 88 N; Cinch, 71 N; MarXmen/MaxFire, 54 N; Sequent, 66 N; and FasT-Fix 360, 60 N. Ethibond was stronger than MarXmen/MaxFire. The mean displacement after 100 cycles was as follows: Ethibond, 2.58 mm; OrthoCord, 2.75 mm; OmniSpan, 2.51 mm; Cinch, 2.65 mm; MarXmen/MaxFire, 3.67 mm; Sequent, 3.35 mm; and FasT-Fix 360, 1.13 mm. The MarXmen/MaxFire showed greater 100-cycle displacement than Ethibond and FasT-Fix 360. No difference in stiffness existed for these devices, and failure mode varied without specific trends. CONCLUSIONS: The biomechanical properties of meniscal repairs using the OmniSpan, Cinch, Sequent, and FasT-Fix 360 devices are equivalent to suture repair techniques. However, the MarXmen/MaxFire meniscal repair device showed significantly lower failure loads and survived less cyclic loading in the human cadaveric meniscus than other tested repairs. CLINICAL RELEVANCE: Most commercially available devices for all-inside meniscal repair using ultrahigh molecular-weight polyethylene suture provide fixation comparable to the classic vertical mattress suture repair technique in human cadaveric meniscus. PMID- 22317798 TI - Arthroscopic partial repair of irreparable large to massive rotator cuff tears. AB - PURPOSE: The aim of this study was to evaluate the outcome of arthroscopic partial repair and margin convergence of irreparable large to massive rotator cuff tears. METHODS: Between January 2003 and July 2008, 27 patients who met the inclusion criteria underwent arthroscopic partial repair and margin convergence of irreparable large to massive rotator cuff tears. An irreparable tear was defined as a tear with a minimum anterior-to-posterior width of 3 cm or larger, where it was not feasible to completely cover the humeral head with the cuff at the time of surgery. RESULTS: The mean preoperative tear size was 42.1 +/- 6.2 mm. The mean size of the postoperative residual defect in the repaired tendon along the medial margin of the greater tuberosity was 12.0 +/- 5.5 mm. All shoulder scores showed improvement. The Simple Shoulder Test improved from 5.1 +/ 1.2 to 8.8 +/- 2.1 (P < .001), the Constant score from 43.6 +/- 7.9 to 74.1 +/- 10.6 (P < .001), and the University of California, Los Angeles score from 10.5 +/ 3.0 to 25.9 +/- 5.0 (P < .001). Both Constant and University of California, Los Angeles shoulder scores also showed an inverse correlation with defect size. We compared muscle strength between the affected and contralateral sides and found that the strength of the affected side was not restored to the same level as the contralateral side (P < .001). CONCLUSIONS: Arthroscopic partial repair and margin convergence showed satisfactory short-term outcomes in irreparable large to massive rotator cuff tears. Thus it is suggested that, even in a large to massive tear that appears irreparable, attempting to repair it as much as possible to possibly convert it into a functional rotator cuff tear by re creating a balanced forced couple can be helpful in reducing pain, as well as improving functional outcomes. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 22317799 TI - Warfarin genotyping in a single PCR reaction for microchip electrophoresis. AB - BACKGROUND: Warfarin is the most commonly prescribed oral anticoagulant medication but also is the second leading cause of emergency room visits for adverse drug reactions. Genetic testing for warfarin sensitivity may reduce hospitalization rates, but prospective genotyping is impeded in part by the turnaround time and costs of genotyping. Microfluidics-based assays can reduce reagent consumption and analysis time; however, no current assay has integrated multiplexed allele-specific PCR for warfarin genotyping with electrophoretic microfluidics hardware. Ideally, such an assay would use a single PCR reaction and, without further processing, a single microchip electrophoresis (ME) run to determine the 3 single-nucleotide polymorphisms (SNPs) affecting warfarin sensitivity [i.e., CYP2C9 (cytochrome P450, family 2, subfamily C, polypeptide 9) *2, CYP2C9 *3, and the VKORC1 (vitamin K epoxide reductase complex 1) A/B haplotype]. METHODS: We designed and optimized primers for a fully multiplexed assay to examine 3 biallelic SNPs with the tetraprimer amplification refractory mutation system (T-ARMS). The assay was developed with conventional PCR equipment and demonstrated for microfluidic infrared-mediated PCR. Genotypes were determined by ME on the basis of the pattern of PCR products. RESULTS: Thirty five samples of human genomic DNA were analyzed with this multiplex T-ARMS assay, and 100% of the genotype determinations agreed with the results obtained by other validated methods. The sample population included several genotypes conferring warfarin sensitivity, with both homozygous and heterozygous genotypes for each SNP. Total analysis times for the PCR and ME were approximately 75 min (1-sample run) and 90 min (12-sample run). CONCLUSIONS: This multiplexed T-ARMS assay coupled with microfluidics hardware constitutes a promising avenue for an inexpensive and rapid platform for warfarin genotyping. PMID- 22317800 TI - Effect of medial meniscus tear and partial meniscectomy on balancing capacity in response to sudden unidirectional perturbation. AB - Medial meniscus tears and medial partial meniscectomies can damage or remove mechanoreceptors in the meniscus; this inevitably affects knee joint proprioception. Few studies have addressed this subject and none has examined balance in response to sudden perturbation, which requires complex coordination. This study investigated changes in balance in response to sudden unidirectional perturbations after a medial meniscus tear and medial partial meniscectomy in the 3rd and 12th postoperative months. We compared balancing capacity after sudden unidirectional (horizontal) perturbation in 20 control subjects and 20 patients with a medial meniscus tear. Patients were re-examined 3 and 12 months postoperatively. Balancing ability after unidirectional perturbation was assessed by the Lehr's damping ratio in provocation tests. Meniscus tear significantly reduced the Lehr's damping ratio while standing on the affected leg (p=0.0001) and impaired the posture while standing on both legs (p=0.0007). After partial medial meniscectomy, the Lehr's damping ratio was only significantly reduced while standing on the affected side compared to controls (p<0.01). The results indicated that meniscus tears reduced patients' ability to respond to unidirectional perturbation and adapt to environmental changes. Even 1 year postoperatively, balance after sudden unidirectional perturbation on the affected side was weaker than that of controls. PMID- 22317801 TI - Preventing noncommunicable diseases-beyond lifestyle. PMID- 22317802 TI - Should preregistration of epidemiologic study protocols become compulsory? Reflections and a counterproposal. PMID- 22317803 TI - Estimation with Cox models: cause-specific survival analysis with misclassified cause of failure. AB - While epidemiologic and clinical research often aims to analyze predictors of specific endpoints, time-to-the-specific-event analysis can be hampered by problems with cause ascertainment. Under typical assumptions of competing risks analysis (and missing-data settings), we correct the cause-specific proportional hazards analysis when information on the reliability of diagnosis is available. Our method avoids bias in effect estimates at low cost in variance, thus offering a perspective for better-informed decision making. The ratio of different cause specific hazards can be estimated flexibly for this purpose. It thus complements an all-cause analysis. In a sensitivity analysis, this approach can reveal the likely extent and direction of the bias of a standard cause-specific analysis when the diagnosis is suspect. These 2 uses are illustrated in a randomized vaccine trial and an epidemiologic cohort study, respectively. PMID- 22317804 TI - A comparison of standard methods with g-estimation of accelerated failure-time models to address the healthy-worker survivor effect: application in a cohort of autoworkers exposed to metalworking fluids. AB - BACKGROUND: Studies of autoworkers exposed to straight metalworking fluids report excess risks of several cancers. These studies, however, have not addressed the healthy-worker survivor effect. Most methods proposed to address this bias do not consider that it may be caused by time-varying confounders affected by prior exposure. G-estimation of accelerated failure-time models was developed to handle this issue but has never been applied to account for the healthy-worker survivor effect. METHODS: We compare results from Cox models and g-estimation in 38,747 autoworkers exposed to straight metalworking fluids. Exposure was defined based on job records and air samples. We examine relationships between duration of exposure and mortality from all causes, cancers, ischemic heart disease, and chronic obstructive pulmonary disease (COPD). RESULTS: In standard models, hazard ratios were elevated for cancers of the larynx, prostate, and rectum, but below or approximately equal to 1.0 for all other outcomes considered. Adjustment for the healthy-worker survivor effect using time off work, employment status, time since hire, and restriction to inactive workers after 15 years of follow-up did not substantially change the hazard ratios. However, g-estimation yielded higher hazard ratios than standard Cox models for most outcomes. Exposure was related to increased risks of mortality from all causes combined, heart disease, COPD, and all cancers, as well as lung and prostate cancers. CONCLUSIONS: G-estimation may provide a better control for the healthy-worker survivor effect than standard methods. PMID- 22317805 TI - Structural nested models, g-estimation, and the healthy worker effect: the promise (mostly unrealized) and the pitfalls. PMID- 22317806 TI - Using marginal structural models to estimate the direct effect of adverse childhood social conditions on onset of heart disease, diabetes, and stroke. AB - BACKGROUND: Early-life socioeconomic status (SES) is associated with adult chronic disease, but it is unclear whether this effect is mediated entirely via adult SES or whether there is a direct effect of adverse early-life SES on adult disease. Major challenges in evaluating these alternatives include imprecise measurement of early-life SES and bias in conventional regression methods to assess mediation. In particular, conventional regression approaches to direct effect estimation are biased when there is time-varying confounding of the association between adult SES and chronic disease by chronic disease risk factors. METHODS: First-reported heart disease, diabetes, and stroke diagnoses were assessed in a national sample of 9760 Health and Retirement Study participants followed biennially from 1992 through 2006. Early-life and adult SES measures were derived using exploratory and confirmatory factor analysis. Early life SES was measured by parental education, father's occupation, region of birth, and childhood rural residence. Adult SES was measured by respondent's education, occupation, labor force status, household income, and household wealth. Using marginal structural models, we estimated the direct effect of early life SES on chronic disease onset that was not mediated by adult SES. Marginal structural models were estimated with stabilized inverse probability-weighted log linear models to adjust for risk factors that may have confounded associations between adult SES and chronic disease. RESULTS: During follow-up, 24%, 18%, and 9% of participants experienced first onset of heart disease, diabetes, and stroke, respectively. Comparing those in the most disadvantaged with the least disadvantaged quartile, early-life SES was associated with coronary heart disease (risk ratio = 1.30 [95% confidence interval = 1.12-1.51]) and diabetes (1.23 [1.02-1.48]) and marginally associated with stroke via pathways not mediated by adult SES. CONCLUSIONS: Our results suggest that early-life socioeconomic experiences directly influence adult chronic disease outcomes. PMID- 22317807 TI - Marginal structural models: the way forward for life-course epidemiology? PMID- 22317808 TI - Stillbirth: still important and still a puzzle. PMID- 22317809 TI - Commentary: perfluorinated chemicals and time to pregnancy: a link based on reverse causation? PMID- 22317810 TI - Maternal exposure to drinking-water chlorination by-products and small-for gestational-age neonates. AB - BACKGROUND: There is concern about possible effects of disinfection by-products on reproductive outcomes. The purpose of this study was to evaluate the association between maternal exposure to chlorination by-products and the risk of delivering a small for-gestational-age (SGA) neonate. METHODS: We conducted a population-based case-control study in the Quebec City (Canada) area. Term newborn cases with birth weights <10th percentile (n = 571) were compared with 1925 term controls with birth weights >=10th percentile. Concentrations of trihalomethanes and haloacetic acids in the water-distribution systems of participants were monitored during the study period, and a phone interview on maternal habits was completed within 3 months after childbirth. We estimated chlorination by-products ingestion during the last trimester of pregnancy and trihalomethanes doses resulting from inhalation and dermal exposure. We evaluated associations between chlorination by-products in utero exposure and SGA by means of unconditional logistic regression with control of potential confounders. RESULTS: When total trihalomethanes and the 5 regulated haloacetic acids concentrations were divided into quartiles, no clear dose-response relationship was found with SGA. However, increased risk was observed when haloacetic concentrations were above the fourth quartile and when either trihalomethanes or haloacetic acids concentrations were above current water standards (adjusted OR= 1.5 [95% confidence interval = 1.1-1.9] and 1.4 [1.1-1.9], respectively). Inhalation and dermal absorption of trihalomethanes did not contribute to this risk, but a monotonic dose-response was found with haloacetic acids ingestion. CONCLUSION: Oral exposure to high levels of chlorination by-products in drinking water could be a risk factor for term SGA. PMID- 22317811 TI - Quantifying transmission of norovirus during an outbreak. AB - BACKGROUND: Healthcare workers are thought to play a role in nosocomial transmission of norovirus, but the level and direction of norovirus transmission between patients and healthcare workers in sustaining transmission during an outbreak have not been quantified. METHODS: We developed a method for finding plausible transmission trees of who acquired their infection from whom. We applied the method to data from an outbreak of norovirus in 4 wards of a psychiatric institution in the Netherlands in 2008. The simulated transmission trees were based on serial intervals for time between symptom onsets, weighted for the number of days that healthcare workers were present. The obtained transmission trees were linked to the Barthel Index, a measure of patient reliance on healthcare in their basic daily activities. RESULTS: The dominant recognized transmission route was from patient to patient (64%), followed by patient to healthcare worker (29%). The overall estimated reproduction number for healthcare workers was low compared with patients (0.25 vs. 1.20; mean difference = 0.95 [95% confidence interval (CI) = 0.60 to 1.30]). The average number of all subsequent cases attributable to the downstream branch of one single infected healthcare worker in the transmission tree was 4.4 compared with 6.5 for cases attributable to one single infected patient (mean difference = 2.1 [95% CI = -4.7 to 8.9]). In the ward with patients requiring the highest level of care from healthcare workers, the attack rate among healthcare workers was highest. CONCLUSION: This approach provides a framework to quantify the magnitude and direction of transmission between healthcare workers and patients during a norovirus outbreak. The utility of this method in outbreaks of other infections and in different settings should be explored. PMID- 22317812 TI - A mapping between interactions and interference: implications for vaccine trials. AB - In this paper, we discuss relationships between causal interactions within the counterfactual framework and interference in which the exposure of one person may affect the outcomes of another. We show that the empirical tests for causal interactions can, in fact, all be adapted to empirical tests for particular forms of interference. In the context of interference, by recoding the response as some function of the outcomes of the various persons within a cluster, a wide range of different forms of interference can potentially be detected. The correspondence between causal interactions and forms of interference extends to encompass n-way causal interactions, interference between n persons within a cluster, and multivalued exposures. The theory for causal interactions provides a complete conceptual apparatus for assessing interference as well. The results are illustrated using data from a hypothetical vaccine trial to reason about specific forms of interference and spillover effects that may be present in this vaccine setting. We discuss the implications of this correspondence for our conceptualizations of interaction and for application to vaccine trials and many other settings in which spillover effects may be present. PMID- 22317813 TI - Postdiagnosis change in bodyweight and survival after breast cancer diagnosis. AB - BACKGROUND: Weight gain after diagnosis is common among women with breast cancer, yet results have been inconsistent among the few studies examining its effects on survival. METHODS: We examined the effects of weight gain on mortality among a cohort of 1436 women diagnosed with a first primary breast cancer in 1996-1997, on Long Island, NY. Subjects were interviewed soon after diagnosis and again after approximately 5 years. Weight was assessed at each decade of adult life; 1 year before, at, and 1 year after diagnosis; and at the time of follow-up. Mortality through the end of 2005 was assessed using the National Death Index. Proportional hazards regression was used while using a selection model to account for missing data. RESULTS: Compared with women who maintained their prediagnosis weight (+/-5%), those who gained more than 10% after diagnosis had worse survival (hazard ratio [HR] = 2.67; [95% credible interval = 1.37-5.05]). The effect was more pronounced during the first 2 years after diagnosis (>5% gain: all-cause mortality in the first 2 years, HR = 5.87 [0.89-47.8] vs. after 2 years, 1.49 [0.85-2.57]); among women overweight before diagnosis (overweight women: all cause HR = 1.91 [0.91-3.88] vs. ideal-weight women, 1.39 [0.62-3.01]); and for women who had gained at least 3 kg in adulthood before diagnosis (>=3-kg gain before diagnosis: 1.80 [0.99-3.26 vs. <3 kg gain before diagnosis: 1.07 [0.30 3.37]. CONCLUSIONS: These results highlight the importance of weight maintenance for women after breast cancer diagnosis. PMID- 22317814 TI - Sex ratio in two generations of the Yusho cohort. PMID- 22317815 TI - Negative control exposures in epidemiologic studies. PMID- 22317817 TI - Leisure time activities and lung cancer. PMID- 22317818 TI - Maternal urinary phthalates and phenols and male genital anomalies. PMID- 22317819 TI - Sleep patterns in pregnancy and fetal growth. PMID- 22317821 TI - AZFb microdeletions and oligozoospermia--which mechanisms? AB - OBJECTIVE: To characterize the deletion patterns and its breakpoints in oligozoospermic patients presenting AZFb and AZFc microdeletions and to understand the recombination mechanisms underlying these microdeletions. DESIGN: Case report. SETTING: Genetics Department of Faculty of Medicine of Porto, Porto, Portugal. PATIENT(S): Two men with severe oligozoospermia and two men with nonobstructive azoospermia identified as having different AZFb+c deletion patterns via Y chromosome microdeletion analysis. INTERVENTION(S): Definition of microdeletions and the fine characterization of the respective breakpoints by sequence-tagged sites (STS) polymerase chain reaction (PCR) and single-nucleotide variant (SNV) PCR. MAIN OUTCOME MEASURE(S): Study of the fine structure of the Y chromosome and discussion of the putative mechanisms involved in each microdeletion pattern. RESULT(S): From the four patients studied, three deletion patterns were identified: IR4/distal-P2 (25%; 1 of 4), P5/proximal-P1 (50%; 2 of 4), and P5/distal-P1 (25%; 1 of 4). Although severe oligozoospermia is normally associated with AZFc, a complete AZFb deletion was found in one case. CONCLUSION(S): Analysis of these patients has revealed a new putative region that may be involved in spermatogenesis conservation. PMID- 22317822 TI - Anti-genotoxic role of eicosapentaenoic acid against imazalil-induced DNA damage in vitro. AB - Eicosapentaenoic acid (EPA) is a polyunsaturated n-3 fatty acid and is essential to the health of mammals. Recent data show that EPA can act as anti-mutagenic agent. On the other hand, pesticides comprise a new and important class of environmental pollutants nowadays. Imazalil (IMA), a commonly used fungicide in both agricultural and clinical domains is suspected to produce very serious toxic effects in vertebrates. The present study investigated the anti-genotoxic effect of EPA against the genotoxic damage induced by IMA on cultured human lymphocytes using chromosomal aberration (CA) and micronucleus (MN) tests as cytogenetic endpoints. Peripheral blood cells were treated in vitro with varying concentrations of EPA (2.5, 5, 10, 20 and 40 MUg/ml), tested in combination with IMA (336 MUg/ml). Our results revealed that the rates of CAs and MNs in lymphocytes were significantly (p < 0.05) increased by IMA as compared to the controls. The results also showed that EPA alone was not genotoxic. Moreover, when combined with IMA treatment, EPA reduced the frequencies of CAs and MNs. A clear dose-dependent decrease in the genotoxic damage of IMA was observed, suggesting a genoprotective role of EPA. In conclusion, our data may have an important application for the protection of cultured human lymphocyte from the genetic damage and repercussions induced by agricultural and industrial chemicals hazardous in people. PMID- 22317823 TI - Lethality, accumulation and toxicokinetics of aluminum in some tissues of male albino rats. AB - In the present work, the lethality percentiles including median lethal doses (LD50), accumulation, distribution and toxicokinetics of aluminum in the liver, kidney, intestine, brain and serum of male albino rats, following a single oral administration were studied throughout 1, 3, 7, 14 and 28 days. The estimated LD50 at 24 h was 3.45 g Al/kg body weight (b.wt.). The utilized dose of Al was 1/50 LD50 (0.07 g Al/kg b.wt.). Aluminum residues, in Al-treated rats, were significantly decreased in response to the experimental periods and were negatively correlated with time. In addition, the hepatic, renal, intestinal, brain and serum Al contents were significantly higher than the corresponding controls at all experimental periods, except the brain that showed significant depletion when compared with its corresponding control after 28 days. Kinetically, the highest average of Al area under concentration - time curves (AUCtotal, MUg/g day) and area under moment concentration - time curves (AUMCtotal, ug/g day(2)) recorded in the brain followed by kidney, serum, intestine and liver. The longest elimination half-life time (t 1/2, day) and the mean residence time (MRT, day) were recorded in the brain followed by the liver, kidney, serum and intestine. On the other hand, the slowest clearance rates (Cls, L/day) of Al, in order, were recorded in brain, kidney, serum, intestine and the liver. The elimination rate constant (Lz, day(-) (1)) of Al from the brain was less than that in the intestine and serum was less than that in the liver and kidney. The computed maximum concentrations (C max) of Al in the intestine > kidney > serum > brain > liver were recorded after 3, 3.8, 2.2, 5.4 and 3.8 days, respectively. The computed starting concentration (C 0, MUg) of Al in serum was higher than its level in the intestine followed by the brain, kidney and liver. PMID- 22317825 TI - RETRACTED: Biochemical changes in the Beluga Huso huso exposed to acute crude diesel oil. PMID- 22317824 TI - Determination of protective role of selenium against aflatoxin B1-induced DNA damage. AB - Selenium is an essential mineral for a healthy life. Appropriate doses of it may undertake a protective role in the organism. In this study, the protective role of selenium (Se(4+)) against aflatoxin B1 (AFB1)-induced DNA damage was determined using random amplified polymorphic DNA on two plants including Vicia faba and Zea mays. It was observed that the concentrations of 0.1, 0.2 and 0.4 ppm of AFB1 have increased polymorphism value, total chlorophyll inhibition rate (IRc, %) and total protein IR (IRp, %). Unlike protein, chlorophyll contents and genomic template stability were decreased. With the addition of different concentrations (0.8 and 80 ppm) of Se(4+) to the treated samples with AFB1, the values return to normal. An 800-ppm concentration of Se(4+), on the contrary, could not inhibit the toxicity of AFB1 but caused an increase in toxicity level of AFB1/enhanced the toxicity level of AFB1. Results suggested that Se(4+) has an antagonistic effect against AFB1 toxicity and that the degree of antagonistic effect of Se(4+) against AFB1 was related to its concentration. PMID- 22317826 TI - Genotoxicity assessment in smokeless tobacco users: a case-control study. AB - India has a long history of tobacco, which includes chewing tobacco and smoking tobacco in various forms. Initially, the smokeless tobacco chewing habit was seen among the majority of the farmers who cultivated tobacco; but in recent years, smokeless tobacco is available in many forms and is cheaper as well and hence it is widely being used among literate and illiterate people. The subjects of our study are living in hilly regions of Yerkaud in Salem district, South India. Most of the inhabitants of our study area are illiterate and more particularly they are unaware of the health effects due to tobacco use. Recent epidemiological reports have strongly indicated the association of cancer risk with usage of smokeless tobacco. The prime aim of our study is to evaluate the genotoxic effects of tobacco use by analysing the cytogenetic end points such as chromosome aberrations in peripheral blood and micronucleus in peripheral blood and buccal cells. About 85 smokeless tobacco users were enrolled for the study and same numbers of age- and sex-matched nontobacco users were also enrolled to serve as controls. The result of our study revealed that tobacco users displayed varied levels of elevated chromosomal damage and micronucleated cells than nontobacco users. The variation in the extent of genetic damage was dependent on the duration of the tobacco use. In conclusion, this study might be helpful in creating awareness on the hazards of the smokeless tobacco products among the global population as a whole for those who chose such products as a cheap alternative to tobacco smoke. PMID- 22317827 TI - The antitumor effects of tetrodotoxin and/or doxorubicin on Ehrlich ascites carcinoma-bearing female mice. AB - The study aimed to investigate the antitumor effect of tetrodotoxin (TTX) and/or doxorubicin (DOX) on Ehrlich ascites carcinoma (EAC)-bearing mice through the investigated biochemical parameters. TTX and/or DOX with or without N acetylcystiene were administrated after 10 days into EAC-female mice for a period of 2 weeks in six equal doses. Treatment with TTX or DOX caused a significant decrease in the mean tumor weight and an increase in the cumulative mean survival time when compared with EAC group. All the treatments reduced the elevated liver tumor markers and increased liver antioxidant enzymes under investigation in comparison with EAC. Hepatic cells, suffered severely from degeneration and karriolysis in EAC group, revealed some improvement as appearance of healthy hepatocytes by TTX treatment. The present results suggested that TTX had a more powerful inhibitor effect on EAC growth than DOX and TTX plus DOX treatments reflected by antitumor biochemical and histological studies. PMID- 22317828 TI - Toxic effects of some synthetic food colorants and/or flavor additives on male rats. AB - The objective of the present work was to evaluate the broadest toxic effect of some synthetic additives of colorants and/or flavors on different body organs and metabolic aspects in rats. A number of chemical food color and flavor additives are routinely added during processing to improve the aesthetic appearance of the dietary items. However, many of them are toxic after prolonged use. In this experiment, a total of 100 male albino rats of Spargue Dawley strain were divided into 10 groups: G(1) was fed basal diet and served as control, G(2): basal diet + Brilliant blue (blue dye, No. 2, 124 mg/kg diet), G(3): basal diet + carmoisine (red dye, No. 3, 70 mg/kg diet), G(4): basal diet + tartrazine (yellow dye, FD & C yellow No. 5, 75 mg/kg diet), G(5): basal diet + trans-anethole (4.5 g/kg diet) G(6): basal diet + propylene glycol (0.25 g/kg diet), G(7): basal diet + vanillin(1.25 g/kg diet), G(8): basal diet + Brilliant blue + propylene glycol, G(9): basal diet + carmoisine + trans-anethole, G(10): basal diet + tartrazine + vanillin for 42 successive days. All food colorants mixed with or without flavor additives induced a significant decrease in body weight, hemoglobin concentration and red blood cell count. Also there was a significant decrease in reduced glutathione content; glutathione-S-transferase and superoxide dismutase activities in both blood and liver compared to control group. On the other hand, a significant increase in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase activities, bilirubin, urea, creatinine, total protein and albumin were observed in all test groups when compared to control group. Finally, it is advisable to limit the uses of these food colorants and/or food flavor additives especially those used by children. PMID- 22317829 TI - Function of lipids - their fate in contact lens wear: an interpretive review. AB - Lipids play a vital role in the body at many interfaces. Examples include the lubrication of articulating joints by synovial fluid, the coating of the lung by pulmonary surfactant and the functions of the tear film in the protection of the anterior eye. The role of the lipids is similar at each site - acting as boundary lubricants and reducing surface and interfacial tension. This review focuses on how and why contact lens wear can disrupt the normal function of lipids within the tear film and explains how the otherwise advantageous presence and function of tear lipids can become disadvantageous, causing problems for the wearer. Because the contact lens is some ten times thicker than the tear film, lipids deposited on the anterior surface become immobilised, reducing lipid turnover and thus leading to prolonged exposure to oxygen and light with consequent generation of degradation products. These degraded lipids reduce lens wettability and have additionally been linked to problems of contact lens discomfort and intolerance. Lipid problems are influenced by the thickness of the lens, the material, surface modification, mode of wear and ultimately the subject. The most influential of these variables is frequently the subject. PMID- 22317830 TI - An interarterial course of anomalous coronary artery and an alternative surgical option. AB - An interarterial course of anomalous left main coronary artery originating from the right aortic coronary sinus of valsalva is a rare condition among anomalous aortic origin of the coronary artery. Various surgical options are available. We performed an alternative procedure, that is, mobilisation of the pulmonic root, pulmonary bifurcation, and plication of the pulmonic root adjacent to the left main coronary artery, in a 12-year-old boy. Favourable results were achieved after 43 months of follow-up. PMID- 22317831 TI - Electronic transport through zigzag/armchair graphene nanoribbon heterojunctions. AB - The electronic transport properties of a graphene nanoribbon (GNR) are known to be sensitive to its width, edges and defects. We investigate the electronic transport properties of a graphene nanoribbon heterojunction constructed by fusing a zigzag and an armchair graphene nanoribbon (zGNR/aGNR) side by side. First principles results reveal that the heterojunction can be either metallic or semiconducting, depending on the width of the nanoribbons. Intrinsic rectification behaviors have been observed, which are largely sensitive to the connection length between the zGNR and aGNR. The microscopic origins of the rectification behavior have been revealed. We find that the carrier type can alter from electrons to holes with the bias voltage changing from negative to positive; the asymmetrical transmission spectra of electrons and holes induced by the interface defects directly results in the rectification behavior. The results suggest that any methods which can enhance the asymmetry of the transmission spectra between holes and electrons could be used to improve the rectification behavior in the zGNR/aGNR heterojunction. Our findings could be useful for designing graphene based electronic devices. PMID- 22317832 TI - Rare LEDGF/p75 genetic variants in white long-term nonprogressor HIV+ individuals. PMID- 22317833 TI - Boron delta-doped (111) diamond solution gate field effect transistors. AB - A solution gate field effect transistor (SGFET) using an oxidised boron delta doped channel on (111) diamond is presented for the first time. Employing an optimised plasma chemical vapour deposition (PECVD) recipe to deposit delta layers, SGFETs show improved current-voltage (I-V) characteristics in comparison to previous similar devices fabricated on (100) and polycrystalline diamond, where the device is shown to operate in the enhancement mode of operation, achieving channel pinch-off and drain-source current saturation within the electrochemical window of diamond. A maximum gain and transconductance of 3 and 200MUS/mm are extracted, showing comparable figures of merit to hydrogen-based SGFET. The oxidised device shows a site-binding model pH sensitivity of 36 mV/pH, displaying fast temporal responses. Considering the biocompatibility of diamond towards cells, the device's highly mutable transistor characteristics, pH sensitivity and stability against anodic oxidation common to hydrogen terminated diamond SGFET, oxidised boron delta-doped diamond SGFETs show promise for the recording of action potentials from electrogenic cells. PMID- 22317834 TI - Paper supported immunosensor for detection of antibiotics. AB - Paper supports were used to develop a simple, inexpensive, fast and sensitive electrochemical immunosensor for the analysis of antibiotic residues in milk samples, where single-walled carbon nanotubes (SWNTs) and a simple dip-dry coating method were employed to prepare the highly sensitive biosensor. Well dispersed SWNTs were impregnated with an antibody against neomycin to obtain a composite coating solution, followed by dipping the filtration paper in the solution to fabricate the sensitive biosensor which had high electrical conductivity. Based on the impedance change in the entire paper supported biosensor with increased concentrations of neomycin, the limit detection of the optimized method was 0.04 ng mL(-1) and a linear detection range from 0.2 to 125 ng mL(-1), well below the European Union regulations for neomycin in this matrix. This paper supported biosensor was applied to determine neomycin in milk samples after a simple sample treatment, with spiked recoveries which ranged from 93.25 to 110.47%. A variety of antibiotic residues in milk samples could be determined following similar sensor preparation. PMID- 22317835 TI - Electrochemical determination of microRNA-21 based on graphene, LNA integrated molecular beacon, AuNPs and biotin multifunctional bio bar codes and enzymatic assay system. AB - MicroRNAs (miRNAs), a kind of small, endogenous, noncoding RNAs (~22 nucleotides), might play a crucial role in early cancer diagnose due to its abnormal expression in many solid tumors. As a result, label-free and PCR amplification-free assay for miRNAs is of great significance. In this work, a highly sensitive biosensor for sequence specific miRNA-21 detection without miRNA 21 labeling and enrichment was constructed based on the substrate electrode of dendritic gold nanostructure (DenAu) and graphene nanosheets modified glassy carbon electrode. Sulfydryl functionalized locked nucleic acid (LNA) integrated hairpin molecule beacon (MB) probe was used as miRNA-21 capture probe. After hybridized with miRNA-21 and reported DNA loading in gold nanoparticles (AuNPs) and biotin multi-functionalized bio bar codes, streptavidin-HRP was brought to the electrode through the specific interaction with biotin to catalyze the chemical oxidation of hydroquinone by H(2)O(2) to form benzoquinone. The electrochemical reduction signal of benzoquinone was utilized to monitor the miRNA-21 hybridization event. The effect of experimental variables on the amperometric response was investigated and optimized. Based on the specific confirmation of probe and signal amplification, the biosensor showed excellent selectivity and high sensitivity with low detection limit of 0.06 pM. Successful attempts are made in miRNA-21 expression analysis of human hepatocarcinoma BEL 7402 cells and normal human hepatic L02 cells. PMID- 22317836 TI - DNA-decorated nanoparticles as nanosensors for rapid detection of ascorbic acid. AB - We designed an assay for rapid detection of ascorbic acid (AA) with a DNAzyme cleaving its DNA substrate in the presence of Cu(2+) and AA. The sensor consists of two DNA strands that form a complex between each other. The 5'-end of the DNAzyme binds the substrate DNA via Watson-Crick bonding and the 3'-end binds through formation of a DNA-triplex via Hoogsteen hydrogen bonding. The substrate DNA was prepared by two different methods. In the first case the nucleic acid was modified with fluorescein/dabcyl FRET pair across the cleavage site. In the second case the nucleic acid modified with fluorescein was immobilised on gold nanoparticles. DNAzyme contains a loop forming a complex with Cu(2+) ions. The oxidation of ascorbic acid (AA) with oxygen yields hydrogen peroxide. The latter interacts with Cu(2+) to give hydroxyl radicals. They break substrate DNA in close vicinity to the copper/DNA complex to separate fluorescein from gold nanoparticles leading to the increase in fluorescence intensity. Use of substrate DNA modified with the fluorescein/dabcyl couple allowed to measure AA concentration within 3 min with the detection limit of 2.5 MUM. Employment of gold nanoparticles decorated with fluorescein-modified DNA allowed to improve the detection limit of AA quantification by two orders of magnitude due to enhanced cleavage of DNA catalysed by Au clusters. Fructose, sucrose, glucose, urea, and citric acid did not interfere with our assay even at concentration of 1mM. Good selectivity allowed us to apply our rapid and sensitive assays to detection of AA in vitamin C tablets, urine and orange juice. PMID- 22317837 TI - Short-term audiologic effect of intratympanic gadolinium contrast agent application in patients with Meniere's disease. AB - OBJECTIVES: The aim of this study was to assess whether gadolinium-based contrast agent influences short-term hearing function in patients with Meniere's disease undergoing intratympanically enhanced inner-ear magnetic resonance imaging. DESIGN: This is a prospective cohort study. SETTING: This study was conducted a tertiary referral university hospital, ENT department. PARTICIPANTS: In this study, 21 adult patients with definite, unilateral Meniere's disease were included. According to the criteria of the Committee on Hearing and Equilibrium, all patients were in stage 1 or 2 of the disease, with largely preserved hearing function. OUTCOMES: All patients underwent clinical and audiologic testing before and 24 hours after intratympanic application of gadolinium-based contrast agent. The effects of the contrast medium on the hearing function were assessed by analysis of frequency thresholds, pure-tone average from 500 Hz to 3 kHz, and speech audiometry. RESULTS: Pure-tone average and single-frequency thresholds in audiometry showed no statistically significant difference after the application of intratympanic gadolinium-based contrast agent. Furthermore, speech audiometry scores remained stable after the application of the contrast agent. CONCLUSIONS: This study did not demonstrate clinically significant short-term effects of intratympanic application of gadolinium-based contrast agent on hearing function in patients with Meniere's disease in initial stages. PMID- 22317838 TI - Comparison of repositioning maneuvers for benign paroxysmal positional vertigo of posterior semicircular canal: advantages of hybrid maneuver. AB - OBJECTIVE: The prevalence of benign paroxysmal positional vertigo (BPPV) is becoming more frequent in elderly population. The presence of comorbid factors has to be considered before assessment as well as before commencing any repositioning treatment. Our aims were evaluation of the maneuvers efficacy and evaluation of the applicability of hybrid maneuver (HM) in patients with physical limitation. STUDY DESIGN AND SETTING: This is a randomized study in 2 tertiary referral centers. INTERVENTION: This is a therapeutic intervention. PATIENTS: All consecutive patients with diagnosis of BPPV of posterior canal matching the inclusion criteria were enrolled. Patients underwent treatment soon after the initial diagnosis in all cases with a repositioning maneuver. The maneuver was casually selected among Semont, Epley, and hybrid. Patients were divided into 3 groups according to the maneuver adopted. RESULTS: Eighty-eight patients with posterior canal BPPV were enrolled for treatment. Fisher exact test showed that no statistical differences exist between HM and other maneuvers in terms of efficacy. Latency of repositioning nystagmus appeared longer in HM in comparison with other maneuvers (P < .05). Efficacy of maneuvers used for BPPV decreases in case of cupulolithiasis (P < .0001). We found no relationship between age, sex, and length of disturbance on response to maneuvers. CONCLUSIONS: All maneuvers evaluated demonstrated similar efficacy. The HM, as our data showed, allows us to obtain a good percentage of success similar to most maneuvers used. It is also more comfortable for the patients with hip or neck functional limitation allowing an effective treatment of the posterior canal BPPV. PMID- 22317839 TI - [Bilateral pulmonary hydatidosis in an immigrant patient]. PMID- 22317840 TI - Management of infective endocarditis: challenges and perspectives. AB - Despite improvements in medical and surgical therapies, infective endocarditis is associated with poor prognosis and remains a therapeutic challenge. Many factors affect the outcome of this serious disease, including virulence of the microorganism, characteristics of the patients, presence of underlying disease, delays in diagnosis and treatment, surgical indications, and timing of surgery. We review the strengths and limitations of present therapeutic strategies and propose future directions for better management of endocarditis according to the most recent research. Novel perspectives on the management of endocarditis are emerging and offer hope for decreasing the rate of residual deaths by accelerating the process of diagnosis and risk stratification, reducing delays in starting antimicrobial therapy, rapid transfer of high-risk patients to specialised medico-surgical centres, development of new surgical methods, and close long-term follow-up. PMID- 22317841 TI - HIV and sexually transmitted infections at the borderlands: situational analysis of sexual health in the Brazilian Amazon. AB - OBJECTIVES: The borderlands are considered areas of increased vulnerability to HIV and sexually transmitted infections (STI). The study aimed to determine the STI/HIV prevalence and risk factors in the triple-border area of the Brazilian Amazon. METHODS: A situational analysis of sexual health was conducted in three cities of the Alto Solimoes region. This multicomponent research approach included key informant interviews, participant observations and mapping of places where people meet sexual partners. Volunteers recruited from the 'hot spots' in each city were invited for interview and STI/HIV testing. RESULTS: Over 6 months, 598 participants were recruited, 285 men of median age 28 years (IQR, 23-37) and 313 women of median age 29 years (IQR, 24-37). Overall, 49.3% reported a casual partner during the past 3 months, but only 38.5% reported consistent condom use. The respective prevalences in men and women were Neisseria gonorrhoeae (1.1% and 0.3%), Chlamydia trachomatis (1.4% and 4.8%), high-risk human papillomavirus (14.4% and 24.0%), active syphilis (3.2% and 2.6%), herpes simplex virus type-2 (51.1% and 72.1%), hepatitis B virus (by hepatitis B virus surface antigen) (7.5% and 4.6%), hepatitis C virus (0.7% and 0.7%) and HIV (1.4% and 0.0%). Risk factors for viral STIs included female sex and age. CONCLUSIONS: While the main conditions that contribute to the spread of HIV are in place in the triple-border area, the prevalence of bacterial STIs and HIV are still relatively low, providing a window of opportunity for interventions. PMID- 22317842 TI - Thrombotic microangiopathies: from empiricism to targeted therapies. PMID- 22317843 TI - [Letter on the article: "benfluorex and valvular heart disease"]. PMID- 22317844 TI - [Chronic bone pain: myeloid metaplasia]. PMID- 22317845 TI - [Steroid-induced osteoporosis]. AB - Bone-related steroid involvement is one of the most frequent complications of steroid treatment. Epidemiological data demonstrate that osteoporosis starts early during the treatment, predominantly involves trabecular bone and is correlated to dosage and treatment duration. Mechanisms and consequences of steroid bone involvement are related to osseous and extra-osseous mechanisms. In clinical practice, steroid-induced osteoporosis remains underdiagnosed and undertreated both in preventive and curative approaches. Recently, new molecules as teriparatide and zoledronic acid got indication for the treatment of steroid induced osteoporosis. To guide treatment strategies, several recommendations are available: French, not updated recommendations since 2003 (Afssaps, 2003), European elaborated by the EULAR in 2007 and those of the ACR updated in 2010. PMID- 22317846 TI - Proteomic analysis of stem cell differentiation and early development. AB - Genomics methodologies have advanced to the extent that it is now possible to interrogate the gene expression in a single cell but proteomics has traditionally lagged behind and required much greater cellular input and was not quantitative. Coupling protein with gene expression data is essential for understanding how cell behavior is regulated. Advances primarily in mass spectrometry have, however, greatly improved the sensitivity of proteomics methods over the last decade and the outcome of proteomic analyses can now also be quantified. Nevertheless, it is still difficult to obtain sufficient tissue from staged mammalian embryos to combine proteomic and genomic analyses. Recent developments in pluripotent stem cell biology have in part addressed this issue by providing surrogate scalable cell systems in which early developmental events can be modeled. Here we present an overview of current proteomics methodologies and the kind of information this can provide on the biology of human and mouse pluripotent stem cells. PMID- 22317847 TI - Penetrating autokeratoplasty for unilateral corneal opacification. AB - OBJECTIVE: The aim was to evaluate the efficacy of autokeratoplasty as an alternative to conventional allograft transplantation for the management of corneal blindness in patients with a healthy cornea in the fellow blind eye. METHODS: A retrospective analysis of all consecutive cases of corneal blindness that were treated with autokeratoplasty was undertaken. We describe nine cases in which the healthy, transparent cornea from a blind eye was transplanted onto the fellow eye with a favorable visual potential but an opaque cornea. The parameters evaluated were uncorrected visual acuity, best-corrected visual acuity (BCVA), endothelial cell loss, graft clarity, and complications if any. RESULTS: The median age of the patients was 63 years (range 37-83 years). Intraoperative complications encountered included expulsive hemorrhage (n=1), retrieval of a corneal button unsuitable for transplantation onto the donor defect (n=1), and problems concerning sizing of the corneal graft (n=1). Glycerine-preserved cornea was used in two eyes. All the patients achieved BCVA >20/60 by 3 months postoperatively, and 8 of the 9 patients (88.9%) maintained a clear graft till the last follow-up (12 months-78 months). Endothelial cell loss of 31.4%+/- 6.3%, 33.2%+/-5.9%, 34.7%+/-8.2% was noted at 1, 6, and 12 months, respectively. Accelerated endothelial cell loss after three episodes of traumatic wound dehiscence was responsible for nonimmunological graft failure in one case. CONCLUSIONS: Autokeratoplasty is a viable option in selected cases of corneal blindness as an alternative to conventional allograft transplantation. In the event of adverse events, a backup tissue should be available. PMID- 22317848 TI - A dosimetric evaluation of dose escalation for the radical treatment of locally advanced vulvar cancer by intensity-modulated radiation therapy. AB - The purpose of this planning study was to determine whether intensity-modulated radiation therapy (IMRT) reduces the radiation dose to organs at risk (OAR) when compared with 3D conventional radiation therapy (3D-CRT) in patients with vulvar cancer treated by irradiation. This study also investigated the use of sequential IMRT boost (seq-IMRT) and simultaneous integrated boost (SIB-IMRT) for dose escalation in the treatment of locally advanced vulvar cancer. Five vulvar cancer patients treated in the postoperative setting and 5 patients treated with definitive intent (def-group) were evaluated. For the postoperative group, 3D-CRT and IMRT plans to a total dose (TD) of 45 Gy were generated. For the def-group, 4 plans were generated: a 3D-CRT and an IMRT plan to a TD of 56.4 Gy, a SIB-IMRT plan to a TD of 56 Gy, and a SIB-IMRT with dose escalation (SIB-IMRT-esc): TD of 67.2 Gy. Mean dose and dose-volume histograms were compared using Student's t test. IMRT significantly (all p < 0.05) reduced the D(mean), V30, and V40 for all OAR in the adjuvant setting. The V45 was also significantly reduced for all OAR except the bladder. For patients treated in the def-group, all IMRT techniques significantly reduced the D(mean), V40, and V45 for all OAR. The mean femur doses with SIB-IMRT and SIB-IMRT-esc were 47% and 49% lower compared with 3D-CRT. SIB IMRT-esc reduced the doses to the OAR compared with seq-3D-CRT but increased the D(max.) for the small bowel, rectum, and bladder. IMRT reduces the dose to the OAR compared with 3D-CRT in patients with vulvar cancer receiving irradiation to a volume covering the vulvar region and nodal areas without compromising the dosimetric coverage of the target volume. IMRT for vulvar cancer is feasible and an attractive option for dose escalation studies. PMID- 22317849 TI - [Biopathology of the synovial membrane in psoriatic arthritis]. AB - The study of the pathobiology of the synovium in psoriatic arthritis has identified morphological, cellular and molecular differences from rheumatoid arthritis. Here we review some processes that are more characteristic or have greater intensity in psoriatic arthritis, such as vascular patterns, angiogenesis and the role of the innate immune cells. We highlight in detail the finding that interleukin (IL) 17, whose role in the pathophysiology appears relevant, is produced mainly by mast cells and neutrophils in different target tissues of psoriatic arthritis, as well as the synovium, skin and axial joints. On the other hand, we try to understand the complexity of the study of the pathophysiology of psoriatic synovitis, which presents multiple interactions between cells and molecules that can vary depending on the phenotype and the stage of the disease in each patient and requires a complex methodological approach. PMID- 22317850 TI - Should we use poor prognosis factors to start early treatment in patients with rheumatoid arthritis? PMID- 22317851 TI - Safety and efficacy of methylprednisolone infiltration in anserine syndrome treatment. AB - OBJECTIVE: The anserine syndrome is a common cause of knee pain. Infiltration with glucocorticoids has been evaluated in studies with low level of evidence and there are no published clinical trials to determine its usefulness. The objective of this study was to determine the efficacy and safety of the infiltration of methylprednisolone in the treatment of Anserin Syndrome. METHODS: We conducted a clinical trial in 58 adult patients with anserin syndrome, which presented intra articular pathology ruled that reflected pain in the medial aspect of the knee. The WOMAC scale was assessed at baseline and patients were randomized to receive an infiltration of lidocaine plus 40 mg methylprednisolone acetate (group 1) versus xylocaine plus distilled water (group 2). Both groups received 100mg of diclofenac sodium for 10 days. The WOMAC scale was applied at 4 weeks and adverse events were recorded. RESULTS: Equivalence was demonstrated in both groups for demographic variables and initial clinical evaluation. There was no statistical difference in the three domains of assessment of the baseline WOMAC score. The median baseline WOMAC in group 1 was 32 and in group 2 was 25.5 points. At 4 weeks it was 8 and 6.5 points, which corresponded to an improvement of 61.6 and 62.8% respectively. CONCLUSION: The infiltration with methylprednisolone in anserin syndrome is not superior to placebo in patients taking diclofenac measured by the WOMAC scale at 4 weeks. The incidence of adverse events did not show any differences either. PMID- 22317852 TI - Are high doses of prednisone necessary for treatment of interstitial lung disease in systemic sclerosis? AB - INTRODUCTION: Interstitial lung disease (ILD) as part of systemic sclerosis (SS) is a leading cause of morbidity and mortality. OBJECTIVES: To evaluate the use of intravenous pulse cyclophosphamide combined with low and high doses of prednisone in the treatment of ILD in SS is equally effective. METHOD: An experimental, exploratory and randomized single-blind clinical trial was conducted at Hermanos Ameijeiras Clinical Surgical Hospital from September 2006 to December 2009, including 23 patients with SS and ILD. Two treatment schedules were evaluated and randomly assigned. Group A was composed of 13 patients with a monthly dose of cyclophosphamide (ev) for 6 months and a twice-monthly dose for the remaining 6 months, prednisone (1 mg * kg * day) 4 weeks and then the dose was lowered to 5mg every 2 weeks up to 10mg. Group B: 10 patients with cyclophosphamide (ev), oral prednisone 10mg daily. RESULTS: There are significant differences at onset of CVF and the honeycomb pattern between both groups, where the high dose group was at a disadvantage. At the end of treatment the low dose group achieved improvement of radiologic lesions and the Warrick index, unlike the high dose group. The remaining variables experienced improvement in both groups without marked inequality. Similarly, slight adverse reactions were present in both groups. Two patients dropped out of the study. CONCLUSIONS: A combination of low dose steroids with cyclophosphamide is effective in interstitial lung disease treatment especially in active disease, and results did not showe differences regarding the high dose group but the sample size and the evolutionary severity of high dose patients oblige other studies to verify this data. PMID- 22317853 TI - Benefits of order: the influence of item sequencing on metacognition in moderate and severe traumatic brain injury. AB - The ability to appraise one's own ability has been found to have an important role in the recovery and quality of life of clinical populations. Examinee and task variables have been found to influence metacognition in healthy students; however the effect of these variables on the metacognitive accuracy of adults with neurological insult, such as traumatic brain injury (TBI), remains unknown. Twenty-two adults with moderate and severe TBI and a matched sample of healthy adults participated in this study examining the influence of item sequencing on metacognitive functioning. Retrospective confidence judgments were collected while participants completed a modified version of the Matrix Reasoning subtest. Significant influence of item sequence order was found, revealing better metacognitive abilities and performance when participants completed tasks where item difficulty progressed in order from easy to difficult. We interpret these findings to suggest that the sequencing of item difficulty offers "anchors" for gauging and adjusting to task demands. PMID- 22317854 TI - Multiferroic properties-structure relationships in epitaxial Bi(2)FeCrO(6) thin films: recent developments. AB - We report recent developments in the growth and characterization of epitaxial Bi(2)FeCrO(6) (BFCO) thin films. The body of experimental data stemming mostly from our investigations, and also considering the few available reports from other groups, allows us to explain the origin(s) of the thickness dependence of the multiferroic properties observed. A drastic reduction of the films' magnetization is observed for film thicknesses larger than 80 nm. This decrease in magnetization is attributed to the formation of defects, such as antisites and antiphase boundaries, in the BFCO films. The change in magnetization is accompanied by a BFCO cell expansion, a consequence of the volume increase of the oxygen octahedra surrounding the Fe cations induced by the defects. BFCO films are ferroelectric for all the thicknesses investigated, ferroelectricity being only moderately affected by the film thickness. PMID- 22317855 TI - [Keratotic plaques on the hands]. PMID- 22317856 TI - The tobacco-specific carcinogen NNK induces DNA methyltransferase 1 accumulation in laryngeal carcinoma. AB - Over-expression of DNA methyltransferase 1 (DNMT1) correlates with hypermethylation of tumor suppressor genes (TSGs) in tobacco-induced cancers. The tobacco component nitrosamine 4-(methylnitro-samino)-1-(3-pyridyl)-1-butanone (NNK) increases protein levels of the DNMT1 in human lung cancer. However, the role of DNMT1 expression induced by NNK is not clear during laryngeal carcinogenesis. We investigated DNMT1 expression levels in 101 cases of human laryngeal carcinoma specimens and 54 cases clear surgical margin specimens by reverse transcription polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry (IHC) detection. Then, we analyzed the relationship between the DNMT1 expression and the smoking status of the patients with laryngeal carcinoma. Moreover, we investigated the effects of tobacco carcinogen NNK on DNMT1 expression in Hep-2 cells. We found that DNMT1 mRNA and protein expressions were up-regulated in laryngeal cancer tissues (p<0.05 and p<0.01, respectively). Among the 101 cases, DNMT1 protein from patients with heavier smoking habit had a significant trend of an increase with IHC scores (p<0.01). The overall survival rates of patients DNMT1-positive were significantly lower than those of patients DNMT1-negative (p<0.05). We observed that NNK increased DNMT1 protein levels, not mRNA levels, in cultured Hep-2 cells significantly in both dose- and time dependent manner (p<0.05). These results supported the idea that NNK-induced DNMT1 expression may result from protein stabilization. Increased DNMT1 protein expression may play a critical role in the malignant progression of larynx. PMID- 22317857 TI - Adoption of policies to prevent catheter-associated urinary tract infections in United States intensive care units. AB - BACKGROUND: Little is known about whether recommended strategies to prevent catheter-associated urinary tract infection (CAUTI) are being implemented in intensive care units (ICU) in the United States. OBJECTIVES: Our objectives were to describe the presence of and adherence to CAUTI prevention policies in ICUs, to identify variations in policies based on organizational characteristics, and to determine whether a relationship exists between prevention policies and CAUTI incidence rates. METHODS: Four hundred forty-one hospitals that participate in the National Healthcare Safety Network were surveyed in spring 2008. RESULTS: Two hundred fifty hospitals provided information for 415 ICUs (response rate, 57%). A small proportion of ICUs surveyed had policies supporting bladder ultrasound (26%, n = 106), condom catheters (20%, n = 82), catheter removal reminders (12%, n = 51), or nurse-initiated catheter discontinuation (10%, n = 39). ICUs in hospitals with >= 500 beds were half as likely as those in smaller hospitals to have adopted at least 1 CAUTI prevention policy (odds ratio, 0.52; 95% confidence interval: 0.33-0.86), and ICUs in hospitals where the infection control director reported always having access to key decision makers for planning were more than twice as likely as those with less access to have adopted a policy (odds ratio, 2.41; 95% confidence interval: 1.56-3.72). CONCLUSION: Little attention is currently placed on CAUTI prevention in ICUs in the United States. Further research is needed to elucidate relationships between adherence to CAUTI prevention recommendations and CAUTI incidence rates. PMID- 22317858 TI - Development and validation of rapid use scope test strips to determine the efficacy of manual cleaning for flexible endoscope channels. AB - BACKGROUND: Cleaning of flexible endoscopes is most commonly performed using manual methods that are often performed inadequately. The aim of this study was to validate the sample collection protocol and the Rapid Use Scope Test (RUST) and then assess its usefulness in clinical use. METHODS: The benchmarks for adequate cleaning were protein <6.4 MUg/cm(2), hemoglobin <2.2 MUg/cm(2), and carbohydrate <1.2 MUg/cm(2). Sample collection consisted of flushing 10 mL of sterile reverse osmosis water through the suction-biopsy port to the distal end. Validation of the RUST audit tool included simulated-use and in-use testing in 43 endoscopy clinics across Canada. RESULTS: Simulated-use testing validated that improperly cleaned endoscopes that exceeded the cleaning benchmarks would be flagged by the RUST test. The clinical-use study indicated that 96.6% of 1,489 scope channels tested were RUST negative; however, 19% and 12% of elevator guide wire channels and endoscopic retrograde colangiopancreatography channels, respectively, exceeded the benchmarks. The survey indicated that reprocessing personnel valued a rapid audit tool for assessing compliance with manual cleaning. CONCLUSION: The validated RUST test provides health care users with a rapid audit tool for manual cleaning that can be integrated into the quality program in endoscopy. PMID- 22317859 TI - Outcomes of a consultation service to emergency medicine clinicians for postexposure management of occupational bloodborne pathogen exposures. AB - Potential bloodborne pathogen exposures, many of which occur after hours and are evaluated by emergency medicine physicians, are an important occupational hazard. Emergency medicine physicians might not be as conversant with the latest US Public Health Service guidelines as occupational medicine physicians. This research presents an efficient model in which a single expert occupational medicine physician provides guidance to many emergency medicine clinicians. Outcomes evaluation indicates that the service was widely utilized and highly rated. PMID- 22317860 TI - The results of a 6-year epidemiologic surveillance for ventilator-associated pneumonia at a tertiary care intensive care unit in Saudi Arabia. AB - BACKGROUND: Ventilator-associated pneumonia (VAP) prevention is an important patient safety initiative. We describe the impact of a multidisciplinary surveillance program on VAP rates in a tertiary medical-surgical-trauma intensive care unit (ICU). METHODS: An epidemiologic surveillance program was established in 2003 as a joint project between ICU and Infection Prevention and Control Department to regularly report VAP rates to guide evidence-based VAP preventive strategies. VAP cases were diagnosed according to predefined criteria and prospectively recorded by a research physician. VAP microbiology, risk factors, and outcomes were noted. RESULTS: Of 2,812 ventilated patients, 433 (15.4%) developed VAP corresponding to 15.9 episodes per 1,000 ventilator-days. The rate decreased from 19.1 in 2003 to 6.3 per 1,000 ventilator-days in 2009. On multivariate analysis, VAP was associated with accidental extubation (hazard ratio [HR], 4.11; 95% confidence interval [CI]: 1.93-8.73), trauma versus medical diagnosis (HR, 2.59; 95% CI: 2.07-3.23), chronic obstructive pulmonary disease (HR, 1.55; 95% CI: 1.08-2.22), and neuromuscular blockade (HR, 1.39; 95% CI: 1.07 1.81). The most common isolated pathogens were Gram-negative organisms. VAP patients had longer mechanical ventilation duration, ICU and hospital length of stay, but similar ICU and hospital mortality compared with non-VAP patients. CONCLUSION: The study showed a reduction in VAP rates with active surveillance, reporting and evidence-based preventive strategies and identified several modifiable risk factors, which should be the focus of additional interventions. PMID- 22317861 TI - Creation and biochemical analysis of a broad-specific claudin binder. AB - Claudins (CL) are a family of tetra-transmembrane proteins that are the structural and functional components of tight junctions (TJ). CLs are promising targets for drug development because of their role in mucosal drug absorption and cancer. However, CL-targeted drug development has been delayed because CLs have low antigenicity and preparing CL proteins is difficult. We developed a CL binder by using the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) and a baculoviral display system. After screening CL binders from a C-CPE mutant displaying library by using CL-displaying budded baculovirus (BV) we isolated a C CPE mutant called m19, which bound to CL1, CL2, CL4 and CL5. A 3-dimensional analysis showed that m19 has a structural backbone similar to C-CPE. The charge density of the CL-binding domains of m19 and C-CPE differed, suggesting that electrostatic interactions may occur between m19 and CLs. Treatment of epithelial cells with m19 decreased the paracellular but not transcellular integrity, and m19 enhanced jejunal absorption. Thus, we successfully created a CL binder with broad specificity. These findings will contribute to future preparation of CL binders for CL-targeted drug development. PMID- 22317862 TI - [Annulo-aortic ectasia imaging]. PMID- 22317863 TI - [The Algarve Project: closest to achieving the aims of the Stent for Life initiative in Portugal]. PMID- 22317864 TI - Frequency of serous tubal intraepithelial carcinoma in various gynecologic malignancies: a study of 300 consecutive cases. AB - Serous tubal intraepithelial carcinoma (STIC) has been implicated in the pathogenesis of pelvic serous carcinoma. We hypothesized that, if this is the case, the frequency of STIC should be substantially lower in endometrial serous carcinomas, in nonserous gynecologic malignancies, and in benign gynecologic neoplasms than in ovarian or peritoneal serous carcinomas. From 2007 to 2009 the fallopian tubes of 342 consecutive gynecologic cases were entirely submitted for histology using the Sectioning and Extensively Examining the FIMbriated end protocol. This study included 300 of these cases (277 TAH-BSO, 23 BSO) after exclusion. The hematoxylin and eosin-stained slides from the fallopian tubes were independently reviewed by 2 gynecologic pathologists who were blinded to all other findings; disagreements were resolved by a third pathologist. Among 46 cases of ovarian malignancies, STIC was identified in 6 (18.8%) of 32 cases of serous carcinoma, but not in any other subtype. Similarly, STIC coexisted in 4 (14.3%) of 28 cases of endometrial serous carcinoma; however, no STIC was identified in any of the 74 cases of nonserous endometrial malignancies. STIC was identified in 2 (28.6%) of 7 cases of peritoneal serous carcinoma. No STIC was identified among 15 nongynecologic malignancies, 90 cases of benign conditions, and 27 cases of other conditions including 4 cases of cervical adenocarcinoma in situ and high-grade cervical intraepithelial lesions, 8 cases of endometrial atypical complex hyperplasias, and 15 cases of ovarian borderline tumors. In conclusion, the fallopian tube may be the origin of some pelvic serous carcinomas. Other possibilities that may explain the origin of pelvic high-grade serous carcinoma are discussed. Given that STIC coexisted with 14% of endometrial serous carcinomas, a more unifying theory may be that gynecologic serous carcinomas and STIC are multifocal lesions. PMID- 22317865 TI - A systematic review of papers examining the use of intraoperative frozen section in predicting the final diagnosis of ovarian lesions. AB - This systematic review assesses the accuracy of the frozen section classification of benign and borderline lesions or invasive carcinoma when compared with the final diagnosis on paraffin section. A Pubmed database search identified 18 retrospective cohort studies, published since 2005 that satisfied the criteria, on the critical appraisal sheet of the center for evidence-based medicine, The University of Oxford. The sensitivity, specificity, and negative and positive predictive values suggest that frozen section is more accurate at discriminating between benign lesions and invasive carcinoma than between benign and borderline or borderline lesions and invasive carcinoma and indicate a tendency to overcall benign tumors as borderline and borderline tumors as invasive malignancies. A narrative review of individual papers and abstracts suggests that this particular difficulty is encountered when dealing with clear cell carcinoma and mucinous lesions of all sorts. This may have greater importance in the future with the introduction of targeted chemotherapy requiring accurate typing to guide the use of genetic analysis. It would be beneficial if future researchers comparing the results of frozen section and paraffin sections presented their results in the context of preoperative assessment of the clinical and radiological findings or the intraoperative appearances of the tumor and abdominal cavity, which would allow the identification of those cases in which the frozen section allowed a refinement of the diagnoses made using these modalities. PMID- 22317866 TI - Histological grading of ovarian clear cell adenocarcinoma: proposal for a simple and reproducible grouping system based on tumor growth architecture. AB - In this study, we aimed to develop a histological grading system for ovarian clear cell adenocarcinoma (CCA), based on the tumor growth architectures. Cases were defined as Group A if >=90% of a tumor examined was composed of well differentiated tubulocystic and/or papillary architectures; Group C if at least 10% of the tumor was composed of very poorly differentiated histology (i.e. solid masses or individual infiltrating tumor cells with no or little glandular/papillary differentiation); and tumors not corresponding to the first 2 descriptions were defined as Group B. The interobserver reproducibility and prognostic value of the assigned groups were analyzed for 159 CCAs from 5 institutions. The level of agreement in assigning the groups between 2 pathologists was 88.7% (=0.82). After consensus was reached, 46 (29%), 79 (50%), and 34 (21%) tumors were classified in Groups A, B, and C, respectively. In early stage cases [International Federation of Gynecology and Obstetrics (FIGO) stage I II], Group A tumors had significantly better outcomes (100% 5-yr survival) than Group B tumors (82% 5-yr survival, P=0.024 by log-rank test) or Group C tumors (56% 5-yr survival, P=0.00054 by log-rank test). Moreover, early-stage Group B tumors had significantly better outcomes than Group C tumors (P<0.001 by a generalized Wilcoxon test). In advanced cases (FIGO stage III-IV), Group A tumors had significantly better outcomes than Group C tumors (52% vs. 16% 5-yr survival, respectively, P=0.043). Group A and C tumors defined with our system were identified to have favorable and unfavorable prognostic factors, respectively, independent of the clinical stage of the disease and presence of residual tumors after the initial surgery. The proposed grouping system could divide patients with CCA into 3 subgroups with distinct prognostic indications, providing a 3 tier histological grading system for ovarian CCA. PMID- 22317867 TI - Aberrant expression of WWOX protein in epithelial ovarian cancer: a clinicopathologic and immunohistochemical study. AB - Epithelial ovarian cancer is the most frequent cause of death from gynecologic cancer. The WW domain-containing oxidoreductase (WWOX) gene is located at 16q23.3 24.1, a region that spans the second most common human fragile site, FRA16D. Abnormalities affecting WWOX at the genomic and/or expression level(s) have been reported in numerous neoplasias and cancer-derived cell lines. The goal of the study was to evaluate WWOX protein expression in epithelial ovarian carcinoma tissues to determine whether they correlated with clincopathologic parameters. We performed WWOX expression analyses by means of immunohistochemistry on 112 epithelial ovarian carcinoma tissues, and ovarian carcinoma-derived SKOV3, 3AO cells. The basic significant level was fixed at P<0.05. Loss of WWOX expression was observed in 32 (28.6%) of 112 ovarian carcinoma samples and was positively correlated with negative estrogen receptor (ER) (P<0.001) and negative progesterone receptor (PR) (P=0.001). A statistically significant correlation was observed between the lack of WWOX expression and the advanced International Federation of Gynecology and Obstetrics (FIGO) stages (P=0.02). Furthermore, negative WWOX staining was significantly correlated with lymph node metastasis (P=0.013), whereas no significant differences were found between WWOX and HER 2/neu staining (P=0.79). WWOX protein expression was moderately detectable in SKOV3 cells but not in 3AO cells. Our results indicate that loss of WWOX expression in epithelial ovarian carcinomas correlates with negative ER, negative PR, advanced FIGO stages, and lymph node metastases. PMID- 22317868 TI - A detailed immunohistochemical analysis of 2 cases of papillary cystadenoma of the broad ligament: an extremely rare neoplasm characteristic of patients with von hippel-lindau disease. AB - We report 2 cases of papillary cystadenoma, a rare neoplasm characteristic of patients with Von Hippel-Lindau (VHL) disease, involving the pelvic soft tissues of women and probably arising within the broad ligament. In only one of the women was there a history of VHL disease. The other woman was investigated for VHL disease after the diagnosis of papillary cystadenoma and all tests were negative. There has been debate as to whether papillary cystadenomas in women are of mesonephric (Wolffian) or of Mullerian origin and to investigate this we undertook a detailed immunohistochemical analysis. Both tumors were positive with AE1/3, Ber EP4, epithelial membrane antigen, CK7, CD10, CA125, CA19.9, calretinin, and vimentin. One exhibited focal nuclear staining with WT1 and PAX8. The tumors were negative with estrogen receptor, progesterone receptor, androgen receptor, CK20, CEA, TTF1, inhibin, RCC marker, and hepatocyte nuclear factor 1beta. Although favoring a mesonephric origin, the immunohistochemical findings are essentially inconclusive and not definitive for either a mesonephric or a Mullerian origin. We believe that patients found to have papillary cystadenoma should be investigated for VHL disease if there is no history of this. This is the second reported example of papillary cystadenoma in a woman not known to have VHL disease and the first in which investigations have excluded this disease. PMID- 22317869 TI - Sclerosing peritonitis associated with a luteinized adult granulosa cell tumor. AB - Sclerosing peritonitis is an uncommon condition that has been reported in patients with luteinized ovarian thecomas, although some pathologists have suggested that the underlying ovarian pathology is not always neoplastic. We now report sclerosing peritonitis in a patient with an uncommon, luteinized variant of an adult granulosa cell tumor. To the best of our knowledge, this association has not been described previously. We suggest that sclerosing peritonitis may result from the release of substances by luteinized ovarian stromal cells, in the context of hyperplasia or neoplasia, which stimulate the proliferation of submesothelial fibroblasts. PMID- 22317870 TI - A surveillance conundrum: a case of 4 distinct primary malignancies in a BRCA-1 mutation carrier. AB - Women with HBOC syndrome present a unique challenge to the oncology community, as will many genetic cancer syndromes yet to be discovered as genetic testing increases in availability. Issues of management and, most importantly, implication are yet to be elucidated. After a diagnosis of epithelial ovarian carcinoma lifelong follow-up is recommended. Given the high recurrence rate and dismal long term prognosis of advanced epithelial ovarian carcinoma this recommendation is more often than not moot. There are no clear guidelines or recommendations for surveillance designed for women with disease free survival greater than five years. This case presents a unique scenario of a woman with predictable disease that remains unpreventable. PMID- 22317871 TI - Coexistence of struma ovarii and serous cystadenoma of the ovary. PMID- 22317873 TI - PAX2 loss by immunohistochemistry occurs early and often in endometrial hyperplasia. AB - Immunohistochemical markers to assist in the diagnosis and classification of hyperplastic endometrial epithelial proliferations would be of diagnostic use. To examine the possible use of PAX2 as a marker of hyperplastic endometrium, cases of normal endometrium, simple and complex hyperplasia without atypia, atypical hyperplasia, and International Federation of Gynecology and Obstetrics (FIGO) grade 1 endometrioid carcinomas were stained for PAX2. Two hundred and six endometrial samples were available for interpretation of PAX2 staining. The percentage of cases with complete PAX2 loss (0% of cells staining) increased with increasing severity of hyperplasia: 0% of normal proliferative and secretory endometrium (n=28), 17.4% of simple hyperplasia (n=23), 59.0% of complex hyperplasia (n=83), 74.1% of atypical hyperplasia (n=54), and 73.3% of FIGO grade 1 endometrioid cancers (n=15). Partial loss of PAX2 expression did occur in normal endometrium (17.9%) but in smaller proportions of tissue and was less frequent than in simple hyperplasia (47.8% with partial loss), complex hyperplasia (32.5%), atypical hyperplasia (22.2%), and FIGO grade 1 carcinomas (20.0%). Uniform PAX2 expression was rare in complex (8.4%) and atypical hyperplasia (3.7%) and carcinoma (6.7%). When evaluating loss of PAX2 in histologically normal endometrium adjacent to lesional endometrium in a given case, statistically significant differences in staining were observed for simple hyperplasia (P=0.011), complex hyperplasia (P<0.001), atypical hyperplasia (P<0.001), and FIGO grade 1 endometrioid cancer (P=0.003). In summary, PAX2 loss seems to occur early in the development of endometrial precancers and may prove useful in some settings as a diagnostic marker in determining normal endometrium from complex and atypical hyperplasia and low-grade carcinomas. However, it is not useful in distinguishing between these diagnostic categories. PMID- 22317874 TI - Endometrial intraepithelial neoplasia terminology in practice: 4-year experience at a single institution. AB - An alternative WHO classification system for endometrial precancers and hyperplasia separates a lesion called endometrial intraepithelial neoplasia (EIN) from diffuse hormonal effects and cancer, resulting in a 3-category system. EIN is a localized lesion with objective histologic criteria, characterized by monoclonal growth of mutated cells, and associated with a 45-fold elevated cancer risk. This study summarizes our department's experience with EIN diagnoses in the 4 years since conversion to the new terminology. We identified all reports from endometrial samples diagnosed as EIN or including the terms "gland crowding" or "atypia" since conversion and obtained follow-up information from subsequent pathology specimens or clinic notes (82%). The diagnoses were reported by a mixture of pathologists, the majority of whom are not subspecialized to gynecologic pathology and the slides were not reviewed. Overall, 17.1% of women with EIN had carcinoma and 34.9% had either carcinoma or persistent EIN. The proportion of women with EIN or cancer on follow-up did not trend with years since adoption of EIN terminology. The median age at the time of diagnosis was 55 years in an overall population of women who underwent sampling at a median age of 47 years. The median follow-up time was 4 months. All cancers were of endometrioid histology; all but 2 were International Federation of Gynecology and Obstetrics grade 1. In comparison with a previous reproducibility study among expert pathologists on a comparable population from our department, these results for general pathologists show a higher false positive rate for subsequent cancer. PMID- 22317875 TI - Myometrial xanthomatosis: possible relationship to prior pregnancy procedure. AB - We report 3 unique cases of extensive myometrial infiltration by foamy histiocytes in uteri removed for benign conditions. The histologic findings were similar and consisted of diffuse infiltration of myometrium by clusters, cords, and sheets of CD163-positive histiocytes with no other significant inflammatory cell component. Most of the histiocytes had pale, vacuolated, or foamy cytoplasm, but in 1 case eosinophilic granular cytoplasm was also present. In all cases, the nuclei were small and eccentric. No mitotic figures were identified. All cases involved young, parous women who had remote prior surgical interventions involving the uterus; 2 patients had a prior cesarean section and 1 had a prior therapeutic abortion. There was no associated neoplastic or infectious condition in any of the cases, and no patient had a prior history of pelvic inflammatory disease. Although we were unable to obtain more detailed obstetric history, an exuberant and persistent reaction to the surgical procedure and/or to a carrier substance for uterotonic intramyometrial injection may be the basis for this unusual reaction, which we designate as myometrial xanthomatosis. PMID- 22317876 TI - Uterine leiomyosarcoma producing granulocyte colony stimulating factor. AB - Uterine leiomyosarcoma associated with the paraneoplastic production of granulocyte-colony stimulating factor (GCSF) is extremely rare. No case has been reported to date in the English literature. We describe a case of a 56-year-old female with recurrent uterin leiomyosarcoma, associated with leukocytosis (19100/mm) and an elevated serum GCSF (33.0 pg/ml). Tumore histology was consistent with a well differentiated leiomyosarcoma with marked neutrophilic infiltration of the lung and spleen metastases. tumor cells were distinctly positive for GCSF on immunohistochemistry. These findings confirmed the diagnosis of a GCSF-producting uterine leiomyosarcoma with a paraneoplastic leukocytosis. PMID- 22317877 TI - Prevalence of human papillomavirus in women without cervical cancer: a population based study in Eastern India. AB - Despite the high incidence of cervical cancer, population-based data on prevalence of human papillomavirus (HPV) are limited in India. This study aimed to evaluate the prevalence of any HPV type and type-specific prevalence of HPV 16/18 in women without cervical cancer. HPV viral load was measured and correlated with cytologic abnormalities of the cervix. A total of 2501 women between 25 and 65 years of age and without cervical cancer were screened by pap smear cytology. HPV DNA was detected from cervical scrapes by nested polymerase chain reaction. Detection of HPV 16/18 was carried out by polymerase chain reaction using type-specific primers and was confirmed by Southern hybridization. Viral load was determined by absolute real-time polymerase chain reaction. Population prevalence of any HPV was found to be 9.9%. The risk of HPV infection was higher in women aged 25 to 34 years (odds ratio, 1.11), in married women below 20 years of age (odds ratio, 1.80), and in women with parity >=4 (odds ratio, 1.04). Prevalence of HPV 18 (1.4%) was greater than that of HPV 16 (0.6%) in the overall screened population. High-grade squamous intraepithelial lesion cytology was more frequent in women infected with HPV 16 than in those infected with HPV 18 and other types. A gradual increase in HPV copy numbers was associated with progressive cytologic severity. In this study, HPV prevalence is comparable to HPV prevalence reported by other studies among Indian and Asian women. Although the prevalence of HPV 18 was more than that of HPV 16, type 16 infection was associated with higher oncogenicity. PMID- 22317878 TI - Primary vaginal mucinous adenocarcinoma of gastric type arising in adenosis: a report of 2 cases, 1 associated with uterus didelphys. AB - We report 2 cases of primary vaginal mucinous adenocarcinoma arising in adenosis in nondiethylstilbestrol-exposed women, 1 with uterus didelphys. Both tumors exhibited morphologic and immunohistochemical features (MUC6 and/or HIK 1083 positivity) identical to the recently described cervical gastric-type adenocarcinoma, a subtype of mucinous adenocarcinoma that is non-human papillomavirus related and possibly related to adenoma malignum. Both neoplasms were intensely p53 positive, suggesting that TP53 mutation may be implicated in their development. We believe that the vaginal tumors arose from adenosis through atypical adenosis, as benign and atypical glands were present at the periphery of the neoplasms. In reporting these cases, we discuss atypical adenosis and other types of non-diethylstilbestrol-associated vaginal adenocarcinomas. At least 9 other examples of primary vaginal, or more uncommonly cervical, adenocarcinomas arising in non-diethylstilbestrol-exposed women with congenital genitourinary malformations have been reported, suggesting a probable causal association between congenital malformation, vaginal adenosis, and vaginal adenocarcinoma. PMID- 22317879 TI - Neurofibroma of the cervix presenting as cervical stenosis in a patient with neurofibromatosis type 1: a case report. AB - Neurofibromatosis type 1 is an autosomal dominant disorder characterized by the presence of cutaneous and subcutaneous neurofibromas as well as deep-seated plexiform neurofibromas. Although unusual, these lesions have been described in the gynecologic tract, including the cervix; however, when arising in this location, they are commonly asymptomatic or present with lower abdominal pain. Cervical neurofibromas presenting as cervical stenosis have not been described. Awareness by both the clinician and the pathologist of a patient's history is of great help when dealing with a specimen of a patient with neurofibromatosis type 1. PMID- 22317880 TI - Effects of the T-786C, G894T, and Intron 4 VNTR (4a/b) polymorphisms of the endothelial nitric oxide synthase gene on the risk of prostate cancer. AB - Several studies have shown that nitric oxide (NO) and nitric oxide synthase (NOS) system plays an important role in carcinogenesis. Endothelial nitric oxide synthase (eNOS) gene polymorphisms significantly affects serum NO concentrations. Studies addressing the relationship between eNOS gene polymorphisms and prostate cancer (CaP) are very scarce. We examined the association between the 3 eNOS gene polymorphisms (T-786C, G894T, and 4a/b) with risk and clinical features of CaP. One hundred seventy patients with CaP (mean age 63.6 +/- 12.4 years) and 340 age matched healthy controls (mean age 64.9 +/- 12.9 years) were recruited in this case-control study. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. For T-786C polymorphism, we found that CC genotype was associated to CaP risk [odds ratio (OR) = 3.62, 95% confidence interval (CI): 1.89-7.74, P = 0.002), high grade tumor (OR = 2.46, 95% CI:1.78-4.72; P = 0.006), and advanced disease (OR = 4.67, 95% CI: 2.64-8.61; P = 0.002). Neither the CaP risk nor clinical features of CaP were associated with the G894T polymorphism. It was found that, compared with 4a/b bb genotype, the 4a/b "a" variant genotypes were associated with an increased risk of CaP in an allele dose dependent manner (OR = 2.12, 95% CI: 1.68 3.44; P = 0.031 for 4a/b ab genotype, and OR = 4.32, 95% CI: 2.21-6.08; P = 0.001 for 4a/b aa genotype). In addition, genotypes with the "a" allele of the eNOS 4a/b polymorphism predispose the patients to high grade (OR = 4.76, 95% CI: 2.74 8.62; P = 0.001) and advanced CaP (OR = 5.28, 95% CI: 3.64-8.72; P = 0.001). Furthermore, the T-Asp-b and C-Asp-b haplotypes were associated with a significantly decreased risk of CaP (OR = 0.44, 95% CI: 0.33-0.77; P = 0.004, and OR = 0.39, 95% CI: 0.26-0.61; P = 0.001, respectively). We found significant differences in genotype distribution and allelic frequencies between CaP patients and controls for the T-786C, and 4a/b eNOS polymorphisms. PMID- 22317881 TI - Do antiplatelets increase the risk of bleeding after endoscopic submucosal dissection of gastric neoplasms? AB - BACKGROUND: It is rarely known whether antiplatelets increase the risk of bleeding after endoscopic submucosal dissection (ESD). OBJECTIVE: To evaluate the effect of antiplatelets on post-ESD bleeding. DESIGN: Retrospective study. SETTING: Single, tertiary-care referral center. PATIENTS: This study involved 1591 gastric neoplasms (815 adenomas and 776 early gastric cancers) in 1503 patients who had ESD between April 2005 and April 2010. INTERVENTION: ESD. MAIN OUTCOME MEASUREMENTS: Overt hematemesis/hematochezia, a drop of hemoglobin >2 g/dL from baseline, or requirement of endoscopic hemostasis, angiographic embolization, and/or transfusion. RESULTS: Of 1591 subjects, 274 took antiplatelets, among whom 102 discontinued them for 7 days or more before ESD. Post-ESD bleeding occurred in 94 subjects including 20 from the continuation group, 6 from the withdrawal group, and 68 from the no-antiplatelet group. In univariate analysis, antiplatelets, early gastric cancer (EGC), comorbidity, and specimen diameter were related to post-ESD bleeding. In multivariate analysis, EGC (odds ratio [OR] 1.839; 95% confidence interval [CI], 1.168-2.896; P = .009), comorbidity (OR 2.246; 95% CI, 1.280-3.939; P = .005), and specimen diameter (OR 2.315; 95% CI, 1.282-4.180; P = .005) were independent risk factors of post-ESD bleeding, whereas antiplatelet usage was not (OR 1.596; 95% CI, 0.877-2.903; P = .126). In subgroup analysis, continuous antiplatelet usage was not found to be an independent risk factor of post-ESD bleeding in multivariate analysis (OR 2.027; P = .146). Among 102 subjects who discontinued antiplatelets, 1 developed an acute cerebral infarction (1.0%). LIMITATION: A retrospective, single-center analysis. CONCLUSION: In ESD for antiplatelet users, continuous administration was not found to have an independent significant association with bleeding. PMID- 22317882 TI - Hyoscine N-butylbromide does not improve polyp detection during colonoscopy: a double-blind, randomized, placebo-controlled, clinical trial. AB - BACKGROUND: Colonoscopy is used for the detection of neoplastic polyps, although a significant miss rate has been reported. Limited data suggest that the administration of the antispasmodic hyoscine N-butylbromide during colonoscopy improves polyp detection. OBJECTIVE: To investigate whether the use of 20 mg hyoscine N-butylbromide intravenously during colonoscopy improves polyp detection or removal. DESIGN: A prospective, double-blind, placebo-controlled, randomized, clinical trial. SETTING: Nonacademic teaching hospital. PATIENTS: This study involved 674 patients who were routinely referred and accepted for either diagnostic or screening colonoscopy. INTERVENTION: Intravenous injection of either 1 mL hyoscine N-butylbromide (n = 340) or 0.9% NaCl solution (n = 334) when withdrawal was started. MAIN OUTCOME MEASUREMENTS: Polyp detection rate (PDR), adenoma detection rate (ADR), and the advanced lesion detection rate (ALDR), 5% trimmed mean number of polyps, mean withdrawal time. RESULTS: The cecal intubation rate was 96%. The PDR, ADR, and ALDR were 56% versus 60%, 30% versus 31%, and 14% versus 14% in the hyoscine N-butylbromide and placebo groups, respectively (all P values > .25). The means of the total number of detected, removed, and harvested polyps per patient were 1.13 versus 1.21, 1.03 versus 1.06, and 0.89 versus 0.89 in the hyoscine N-butylbromide and placebo groups, respectively (all P values > .37). Mean withdrawal time was 561 versus 584 seconds in the hyoscine N-butylbromide and placebo groups, respectively (P = .34). Multivariate analysis demonstrated no effect of hyoscine N-butylbromide on the investigated parameters. LIMITATIONS: Only experienced colonoscopists participated in the study. CONCLUSION: We found no evidence to support the use of hyoscine N-butylbromide during withdrawal of the colonoscope to improve polyp detection or removal. ( CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN25405865.). PMID- 22317883 TI - Targeted cyst wall puncture and aspiration during EUS-FNA increases the diagnostic yield of premalignant and malignant pancreatic cysts. AB - BACKGROUND: Characterization of pancreatic cysts by using EUS-FNA includes chemical and cytologic analysis. OBJECTIVE: To evaluate whether material obtained from FNA of the cyst wall increases diagnostic yield. DESIGN: Prospective series. SETTING: Tertiary referral center. PATIENTS: Consecutive patients with pancreatic cysts referred for EUS-FNA between March 2010 and March 2011. INTERVENTION: FNA was performed with aspiration of cyst fluid for carcinoembryonic antigen (CEA) and cytology, followed by cyst wall puncture (CWP). CWP is defined as puncturing the far wall of the cyst and moving the needle back and forth through the wall to sample the wall epithelium. MAIN OUTCOME MEASUREMENTS: The diagnostic yield for mucinous cystic pancreatic neoplasms by CEA and cytology obtained from cyst fluid compared with cytology obtained from CWP. CEA >=192 ng/mL was considered mucinous. RESULTS: A total of 69 pancreatic cysts from 66 patients were included. Adequate amounts of fluid were aspirated for CEA, amylase, and cytology in 60 cysts (81%). Cellular material adequate for cytologic assessment from CWP was obtained in 56 cysts (81%). Ten (30%) of 33 cysts with CEA <192 ng/mL and negative results of cyst fluid cytology had a mucinous diagnosis from CWP; 6 of 9 (67%) cysts with an insufficient amount of fluid for CEA analysis and cyst fluid cytology had a mucinous diagnosis from CWP. Furthermore, 4 malignant cysts were independently diagnosed by CWP cytology. The incremental diagnostic yield of CWP for mucinous or malignant cysts was therefore 29% (20 of 69 cysts, P = .0001). An episode of pancreatitis (1.45%) occurred. LIMITATION: Lack of surgical criterion standard. CONCLUSIONS: CWP during EUS-FNA is a safe and effective technique for improving the diagnostic yield for premalignant and malignant pancreatic cysts. PMID- 22317884 TI - Developmental physiology of late and moderate prematurity. AB - This is a brief review of the developmental physiology of selected organ and functional systems in moderate and late preterm infants. This outline provides a discussion of the physiological underpinnings for some of the clinical conditions seen in this group of infants, including hypothermia, hypoglycemia, respiratory distress syndrome, transient tachypnea, severe respiratory failure, apnea, feeding difficulties, jaundice, and increased susceptibility to infections. PMID- 22317885 TI - A slowly growing plaque on the lower back: challenge. PMID- 22317886 TI - Evaluation of the ICDP-UEMS Dermatopathology Examination. AB - A detailed analysis of the results of the international annual International Committee for Dermatopathology-Union Europeene des Medecins Specialistes dermatopathology examination was undertaken to identify clues for further improvement. The analysis covered 5 consecutive years (2006-2010) and involved a total of 860 questions (591 common questions and 269 uncommon questions) and 181 participants. It focused on the overall performance of the participants, the performance per part of the examination (theoretical or practical), the performance per format of question (multiple choice or open), the performance per dermatopathological topic, and the performance per professional background (dermatologist or pathologist). The overall performance of the participants was high (on average 75% correct answers in 2006 and 85% correct answers in the subsequent years). In the theoretical part of the examination, the topics of vascular diseases and lichenoid dermatoses scored better than the average of all topics, and the topics of cutaneous lymphoproliferative diseases and melanocytic disorders scored worse. In the first practical part (interpretation of images), dermatologists outperformed pathologists, especially on providing a diagnosis (open question format) of clinical images. In the second practical part (microscopical examination), the topics of vascular diseases, granulomatous diseases, including necrobiotic and degenerative and metabolic diseases scored better than the average of all topics, and the topic of infectious diseases scored worse. The results of this detailed analysis provide an excellent feedback to the examination committee that will be used to consider the adjustment of parts and/or topics of the examination that showed a deviant performance by the participants. In addition, it is recommended to give more attention to the postgraduate education of certain dermatopathological topics, including cutaneous lymphoproliferative diseases, melanocytic disorders, and infectious diseases. PMID- 22317887 TI - BRAF and KRAS mutations in sporadic glomus tumors. AB - Glomus tumors are rare soft tissue neoplasms resembling the normal glomus body, which is a specialized form of arteriovenous anastomosis that regulates heat. The molecular genetics of sporadic glomus tumors has not been studied. We genotyped tumors from 28 patients (16 female patients and 12 male patients) ranging from 13 to 77 years and correlated the results with the tumor site (15 finger/1 hand/4 arm/7 leg/1 eyelid), Ki-67 index, and clinical follow-up. Tumor DNA from paraffin embedded tissue was screened by multiplex polymerase chain reaction and mass spectroscopy, using a panel covering 370 mutations across 30 genes, including AKT1, BRAF, CTNNB1, EGFR, ERBB2, FGFR1/2/3, HRAS, KIT, KRAS, MEK1/2, NRAS, PDGFRA, and PIK3CA. A BRAF V600E mutation was identified in 3 cases, all of which occurred in proximal locations (upper shin, thigh, and upper arm). Two of the patients with BRAF-mutated tumors were quite young (21 and 13 years) and one of the BRAF-mutated tumors recurred in 3 years. A KRAS G12A mutation was found in tumor removed from the finger. Ki-67 index did not correlate with genotype. To our knowledge, this is the first report of oncogenic mutations in sporadic glomus tumors. PMID- 22317888 TI - A worrisome subcutaneous tumor on the forehead of a young woman: challenge. Pencil core granuloma. PMID- 22317889 TI - Pure apocrine nevus: a report of 4 cases. AB - Apocrine nevus is a rare tumor composed of increased mature apocrine glands and ductal structures within a fibrous stroma, located predominantly in the reticular dermis. They have been reported in association with apocrine carcinoma, extramammary Paget disease, and syringocystadenoma papilliferum; less commonly a pure apocrine nevus is identified, unassociated with another apocrine proliferation. Clinically apocrine nevi may appear as solitary or multiple nodules or plaques on the scalp, presternal skin, though they are seen most commonly in the axillae. We describe 4 cases of pure apocrine nevus, all of which appeared clinically as painless or mildly tender skin-colored axillary masses, 2 of which were bilateral. In each case, the lesions appeared in adulthood, and patients denied knowledge of congenital or childhood presence. Patients denied pruritis, discharge, bleeding, or antecedent trauma. Grossly, the specimens consisted of subcutaneous, multicystic ill-defined nodules. Biopsy showed prominent apocrine glands composed of irregularly columnar luminal cells with eosinophilic cytoplasm arranged in a somewhat organoid pattern filling the reticular dermis and extending into the subcutaneous adipose tissue. The glandular luminal cells displayed decapitation secretion. There was a paucity of pilosebaceous units. In one case, the overlying epidermis was papillomatous. The deepest portion of one specimen had lactational change simulating a lactational adenoma. No atypia was seen in either the glandular structures or the stroma. The adjacent sebaceous and eccrine structures were normal. The histologic features and immunohistochemical profile in relation to other apocrine lesions will be reviewed. PMID- 22317890 TI - Subdural hematoma after an epidural blood patch. AB - We report the case of a 37-year-old postpartum patient who developed a contained subacute spinal subdural hematoma causing mass effect on the cauda equina and severe spinal stenosis after undergoing an epidural blood patch for postdural puncture headache. Recovery occurred following administration of oral steroids. PMID- 22317891 TI - Tramadol in pregnancy and lactation. AB - Tramadol produces analgesic effects through both non-opioid and weak opioid activity and is commonly used to treat mild to moderate pain. It has been in use for over 30 years and has a well-established safety profile in the general population. Since tramadol is not licensed for use in pregnancy and lactation, there is limited clinical research on its use in this patient population. A systematic review was undertaken of articles published in English before June 2011, searching Pubmed, Medline, CINAHL, Embase and Cochrane databases using the terms 'tramadol and pregnancy', 'tramadol and breastfeeding', 'tramadol and lactation', and 'tramadol and neonate'. PMID- 22317892 TI - Sleep onset/maintenance difficulties and cognitive function in nondemented older adults: the role of cognitive reserve. AB - This study examined the relationship between cognitive function and sleep onset/maintenance difficulties (SO/MD) in nondemented older adults. We hypothesized that SO/MD negatively impacts cognition and that older adults with lower education would be especially vulnerable to its effects. The sample comprised 549 older adults from the Einstein Aging Study (EAS), a community-based cohort. Participants completed neuropsychological assessment and a sleep questionnaire. Univariate ANCOVAs were performed with cognitive performance as a dependent variable, SO/MD (present or absent) and education (lower: <= 12 years; higher: >12 years) as between-subjects factors, and age, ethnicity, gender, depression, and cardiovascular comorbidies as covariates. Participants were an average age of 79.7 +/- 5.0 years (range = 71-97 years). Fifty-seven percent (n = 314) of the sample met criteria for SO/MD. Among participants with SO/MD, those with lower education performed more poorly on a test of category fluency than participants with higher education (means: 35.2 vs. 41.0; p < .001); among older adults without SO/MD, educational attainment had no measurable effect on cognition (SO/MD * education interaction (F(1,536) = 14.5; p = .00)). Consistent with the cognitive reserve hypothesis, older adults with lower education appear selectively vulnerable to the negative effects of sleep onset/maintenance difficulties on tests of verbal fluency. PMID- 22317893 TI - Effect of antioxidant on the fatty acid composition and lipid oxidation of intramuscular lipid in pressurized pork. AB - To investigate the effect of antioxidants on lipid oxidation and fatty acid composition in pressurized pork, minced pork with or without 1% Na(2)EDTA was pressurized at 500MPa before 7days storage at 4 degrees C. TBARS value, lipid content and fatty acid composition in untreated and high-pressure (HP) treated samples were analyzed. HP treatment induced marked increases in TBARS values and lipolysis of partial phospholipids causing an increase of free fatty acid content. Preferential hydrolysis for polyunsaturated fatty acids (PUFA) in phospholipids resulted in the percentage of PUFA in phospholipids decreasing markedly and thereby that in free fatty acids increasing significantly. Addition of 1% Na(2)EDTA to minced pork before HP significantly decreased the TBARS values in pressurized samples, but did not inhibit the lipolysis of phospholipids, causing the fatty acid composition of phospholipids and free fatty acids to change similarly to those samples without Na(2)EDTA. PMID- 22317894 TI - The branching pattern of villous capillaries and structural changes of placental terminal villi in type 1 diabetes mellitus. AB - Maternal diabetes is associated with changes of the placental structure. These changes include great variability of vascularity manifested by strikingly hypovascular as well as hypervascular terminal villi. In this paper, normal placental terminal villi and pathological villi of type 1 diabetic placentas were compared concerning the structure of villous stroma, spatial arrangement of villous capillary bed and quantitative assessment of capillary branching pattern. Formalin fixed and paraffin embedded specimens of 14 normal and 17 Type 1 diabetic term placentas were used for picrosirius staining, vimentin and desmin immunohistochemistry and confocal microscopy. 3D models of villi and villous capillaries were constructed from stacks of confocal optical sections. Hypervascular as well as hypovascular villi of diabetic placenta displayed changed structure of villous stroma, i.e. the collagen envelope around capillaries looked thinner and the network of collagen fibers seemed less dense. The desmin immunocytochemistry has shown that stromal cells of hypervascular as well as hypovascular villi appeared nearly or completely void of desmin filaments. In comparison with normal villi, capillaries of hypovascular villi had a smaller diameter and displayed a markedly wavy course whereas in hypervascular villi numerous capillaries occurred in reduced stroma and often had a large diameter. The quantitative assessment of capillary branching has shown that villous capillaries are more branched in diabetic placentas. It is concluded that type 1 maternal diabetes enhances the surface area of the capillary wall by elongation, enlargement of diameter and higher branching of villous capillaries and disrupts the stromal structure of terminal villi. PMID- 22317895 TI - Thymic stromal lymphopoietin promotes the proliferation of human trophoblasts via phosphorylated STAT3-mediated c-Myc upregulation. AB - Our previous study has demonstrated that thymic stromal lymphopoietin (TSLP) stimulates trophoblast proliferation and invasion, suggesting TSLP plays an important role in the placentation in early human pregnancy, but the intracellular molecular mechanism is currently unknown. The present study is undertaken to investigate whether the STAT3-c-Myc signaling pathway is involved in TSLP-mediated trophoblast proliferation. Primary human first-trimester trophoblasts were treated with TSLP only, or TSLP combined with different signaling inhibitors (STAT3, STAT5, AKT, and ERK). The levels of STAT3 tyrosine phosphorylation and c-Myc expression were determined by using Western blot analysis, and the proliferation of trophoblasts was analyzed by BrdU cell proliferation assay. JEG-3 cells were transfected with siRNA targeting to c-Myc, and the proliferation was determined in JEG-3 cells treated with TSLP only, or TSLP combined with c-Myc silencing. It was revealed that treatment with TSLP significantly enhanced STAT3 phosphorylation and c-Myc expression in human trophoblasts. The effect of TSLP upregulation on trophoblast proliferation was abrogated completely by either STAT3 inhibitor or c-Myc siRNA silence. We further found that the upregulation of TSLP on c-Myc expression was abrogated completely by the STAT3 inhibitor, which suggests that the intracellular STAT3 phosphorylation is an upstream signal of c-Myc expression in the TSLP-stimulated trophoblast proliferation. These results suggest that TSLP may upregulate c-Myc expression through activation of STAT3 pathway, thereby inducing trophoblast proliferation. PMID- 22317896 TI - Diagnostic flexible bronchoscopy and accessory techniques. AB - We reviewed the most important diagnostic procedures implemented by means of flexible bronchoscopy, including bronchoalveolar lavage, bronchial brushing and biopsy, transbronchial lung biopsy and transbronchial needle aspiration. We reviewed the tools, techniques and potential complications of this examination. PMID- 22317897 TI - Asymmetric magnetoresistance in an exchange bias Co/CoO bilayer. AB - Magnetoresistance (MR) measurements are carried out on a Co(8 nm)/CoO(3.5 nm) bilayer in the exchange bias (EB) state prepared by molecular beam epitaxy. With the applied magnetic field parallel to the current, the EB MR curves show an asymmetric behavior about the minimum, in contrast to the symmetric one for non EB systems. We generalize a well-known analytical expression used for the field dependence of the MR of paramagnets. Our generalization incorporates coercivity and EB in a new phenomenological MR expression. Excellent fits of the latter to the experimental MR data are achieved, showing the way to use MR techniques for the quantitative characterization of EB systems. Furthermore, the temperature dependence of the EB field obtained from MR loops can be described with a power law, which yields a value of 96.6 K for the EB blocking temperature, which is significantly below the Neel temperature of 293 K for bulk CoO. PMID- 22317898 TI - Reversible increase in smoking after withdrawal of ventral capsule/ventral striatum deep brain stimulation in a depressed smoker. PMID- 22317899 TI - Postmenopausal hormone therapy and ductal carcinoma in situ: a population-based case-control study. AB - BACKGROUND AND AIM: The relationship between hormone therapy (HT) and invasive breast cancer has been extensively investigated, but the relationship between HT and in situ breast cancer has received relatively little attention. We examined the relationship between HT and ductal carcinoma in situ (DCIS) among postmenopausal women who participated in a population-based case-control study in Connecticut, USA. METHODS: This analysis included 1179 post-menopausal women (603 controls and 576 cases), who comprised a subset of a population-based case control study that included all incident cases of breast carcinoma in situ (BCIS) in Connecticut and frequency-matched controls by 5-year age intervals. RESULTS: We found no association between DCIS and ever use of any HT (adjusted odds ratio (OR)=0.85, 95% confidence interval (CI): 0.65-1.11); of estrogen alone (adjusted OR=0.93; 95% CI: 0.68-1.29) or of estrogen and progesterone (adjusted OR=0.75; 95% CI: 0.52-1.08). There was also no association between DCIS and current use of these hormones. In addition, estimated risk of DCIS did not increase with duration of use of these preparations. CONCLUSIONS: These results add to a small literature that remains inconclusive. To determine whether HT poses risk of in situ breast cancer, larger studies with greater power and precise control of important covariates (e.g., mammography screening) are needed, as are meta analyses of available data. PMID- 22317900 TI - The kidney in heart failure: friend or foe? AB - Heart failure constitutes a significant source of morbidity and mortality in the United States and its incidence and prevalence continue to grow, increasing its burden on the health care system. Renal dysfunction in patients with heart failure is common and has been associated with adverse clinical outcomes. This complex interaction is characterized by a pathophysiological disequilibrium between the heart and the kidney, in which cardiac malfunction promotes renal impairment, which in turn feeds back for further deterioration of cardiovascular function. Multiple neurohumoral and hemodynamic mechanisms are involved in this cardiorenal dyshomeostasis, including the deficiency of and/or resistance to compensatory natriuretic peptides, leading to sodium retention, volume overload and organ remodeling. Management of patients with cardiorenal dysfunction can be challenging and should be individualized. Emerging therapies must address the impairment of both organs to secure better clinical outcomes. To this end, a multidisciplinary approach is warranted to achieve optimal results. PMID- 22317901 TI - Heart failure with preserved left ventricular function: diagnostic and therapeutic challenges in patients with diastolic heart failure. AB - Heart failure associated with preserved left ventricular ejection fraction (HFpEF) is a condition of increasing importance, not only due to its rising prevalence but also due to the lack of clinical evidence for pharmacologic therapies that are beneficial. Thus, a recent case encountered at the Vanderbilt University Medical Center illustrates the clinical challenges one may encounter in patients with HFpEF. A careful review of the diagnostic challenges of HFpEF or diastolic heart failure, current recommendations for management and a glimpse of upcoming research are presented. PMID- 22317902 TI - A paradigm shift in the treatment of advanced non-small cell lung cancer. AB - Lung cancer is the most common cause of cancer death for men and women worldwide. Nonsmall cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Systemic chemotherapy is a cornerstone of treatment in the management of stage IV NSCLC. First-line chemotherapy typically consists of a platinum-based treatment. The optimum approach to long-term treatment beyond 4 to 6 cycles of chemotherapy is still evolving. Second-line chemotherapy given at the time of disease progression has shown clear survival advantages when compared with best supportive care alone. With the recent increase in the number of active and more tolerable agents available to treat NSCLC, there is renewed interest in the role of continuation of antineoplastic agents (continuation maintenance) or switching to a different agent (switch maintenance) after first-line chemotherapy. This case-based review discusses the role of maintenance chemotherapy in the long-term management of advanced NSCLC. PMID- 22317903 TI - Is TEVAR an answer for long term solution in chronic aortic type B diseases? PMID- 22317904 TI - Identification of intermediates involved in the biosynthetic pathway of 3 mercaptohexan-1-ol conjugates in yellow passion fruit (Passiflora edulis f. flavicarpa). AB - Yellow passion fruit is one of the most well-known tropical fruits and much of its success comes from its typical aroma. Key compounds in explaining yellow passion fruit scent are volatile thiols. These molecules are reported to be present in several fruits and originate from non-volatile precursors. Such free thiols are particularly appreciated in white wines and considerable efforts have been made to try to maximise their production and understand their biosynthesis. Two main precursors have been identified so far: S-glutathionylated and S cysteinylated precursors, the latter originating in the breaking down of the glycyl and glutamyl moieties of the former. Improving knowledge about this pathway is currently one of the main challenges in the field of aroma chemistry. Only S-cysteinylated precursors have been reported in the literature for yellow passion fruit, thus much of the biochemical pathway remains unknown. In this paper a combination of organic synthesis, MS and NMR experiments was developed in order to investigate this pathway in yellow passion fruit. The three missing stages leading to the S-cysteinylated precursor were clearly identified. Both intermediate species between S-glutathionyl and S-cysteinyl 3-mercaptohexan-1-ol were found, suggesting that the plant is capable of activating both metabolic routes. The information gained would appear to be crucial for study of this important pathway and for potentially extending this knowledge to other plants, in particular the grapevine. PMID- 22317905 TI - 5-formylfurfuryl esters from Duabanga grandiflora. AB - 5-Formylfurfuryl esters, duabanganals A-D, together with sixteen known compounds, a known 5-formylfurfuryl ester, latifolinal, eight pentacyclic triterpenes, a benzofuran derivative, an ellagic acid derivative, vanillin, beta-sitosterol, beta-sitosterol glucoside, 3-hydroxy-4-methoxycinnamaldehyde, and 5 formylfurfurol, were isolated from the stem bark of Duabanga grandiflora. The structures of these compounds were elucidated on the basis of spectroscopic analysis. Several of these metabolites were evaluated for cytotoxic activities against six cancer cell lines. PMID- 22317906 TI - Dietary trends in the Middle East and North Africa: an ecological study (1961 to 2007). AB - OBJECTIVE: Middle Eastern and North African countries are undergoing nutrition transition, a transition which is associated with an increased burden of non communicable diseases. This necessitates the evaluation of dietary patterns in these regions. The present study aimed to assess changes in dietary patterns in Middle Eastern and North African countries between 1961 and 2007. DESIGN: Availability of energy and fifteen main food items during 1961-2007 was examined using FAO food balance sheets from the FAOSTAT database. SETTING: Fifteen countries including nine in the Middle East and six in North Africa were selected and the average availability of total energy and different food items in these regions were compared. RESULTS: Over the 47 years studied, energy and food availability (apart from animal fats and alcoholic beverages) has increased in the Middle East and North Africa. In both regions the proportion of energy derived from meat and vegetable oils has increased significantly while that from cereals decreased significantly. In addition, the proportion of energy from milk and dairy products and vegetables has shown an ascending trend in North Africa while the proportion of energy from fruits has shown a descending trend in the Middle East. CONCLUSIONS: The study results reveal an unfavourable trend towards a Westernized diet in the Middle East and, to a certain extent, in North Africa. Tailored nutritional education encouraging healthy eating for prevention of the burden of chronic diseases in these countries seems essential. PMID- 22317907 TI - Detection of human rhinovirus C in fecal samples of children with gastroenteritis. AB - BACKGROUND: Despite recent discovery of the novel human rhinovirus species, HRV C, little is known about the association of HRV-C in diseases other than respiratory tract infections. OBJECTIVES: To investigate the presence of HRV-C in fecal samples of children with gastroenteritis. STUDY DESIGN: 734 fecal samples from hospitalized children with gastroenteritis were subject to picornavirus detection by RT-PCR of the conserved 5'-NCR. Positive samples were subject to VP4 and 3D(pol) gene analysis for species determination. The clinical and molecular epidemiology of HRV-C and other picornaviruses was analyzed. RESULTS: Picornaviruses were detected in 113 (15.4%) of 734 fecal samples from children with gastroenteritis by RT-PCR of 5'-NCR, with 58 containing potential HRVs and 55 containing other enteroviruses. PCR of the VP4 and 3D(pol) regions was positive in 21 and 19 samples respectively (both regions positive in 8 samples). Sequencing analysis showed the presence of HRV-C in four samples, and diverse picornaviruses including HRV-A (n=2), HEV-A (n=2), HEV-B (n=2), HEV-C (n=21) and HPeV (n=2) in other samples, with co-detection of HRV-C and HPeV in one sample. Of the four children with HRV-C detected in fecal samples, three presented with diarrhea in the absence of respiratory symptoms, while one also had acute bronchiolitis. The four HRV-C strains from fecal samples belonged to the existing clade of diverse HRV-C genotypes, indistinguishable from previous respiratory strains. CONCLUSIONS: HRV-C can be detected in fecal samples of children with gastroenteritis, in the absence of respiratory symptoms. This study also represented the first to detect HPeV in our population. PMID- 22317908 TI - HIV-1 mother-to-child transmission and drug resistance among Brazilian pregnant women with high access to diagnosis and prophylactic measures. AB - BACKGROUND: A high-coverage public health prenatal program (70,000 women/year) from central western Brazil/Goias State has represented a unique opportunity for the early diagnosis of HIV-1 and implementation of strategies to prevent mother to-child transmission (MTCT). OBJECTIVES: To investigate MTCT among a prospective cohort of HIV-1 infected mothers/exposed infants. STUDY DESIGN: 142 mothers/their 149 infants (2008-2010) were investigated regarding maternal viral load, CD4(+)cell counts, HIV-1 pol sequences; infants' HIV-1 RNA tests (30/120 days), sequential anti-HIV-1/2 serology. HIV-1 subtypes were assigned by REGA. Transmitted drug resistance was identified by the Calibrated Population Resistance tool, secondary resistance by Stanford HIV-1 Drug Resistance/International AIDS Society databases. RESULTS: Mothers (median age=24 years; 25/142 adolescents) were diagnosed during prenatal care (2008-2010) or previously (1994-2007). Recent cases were younger, mostly asymptomatic. Undetectable viremia and MTCT prophylaxis predominated in formerly diagnosed mothers. Recent cases had higher subtype C prevalence. One naive patient had transmitted resistance; ten antiretroviral-experienced patients had secondary resistance: 6 from MTCT prophylaxis, 4 under HAART. Late disclosure of diagnosis, vaginal delivery, breastfeeding, lack of oral zidovudine were observed in the three MTCT cases (3/149; 2.01%). Two of three infected infants harbored subtype C; infected infants/mothers did not have drug resistance mutations. Two of the transmitting-mothers had viremia <1000 copies/ml. Among exposed-uninfected infants the median time to seroreversion was 12 months. CONCLUSIONS: In this study delayed disclosure of diagnosis, partial/no preventive measures, drug resistance among asymptomatic women under prophylaxis and MTCT in low viremic mothers raise concerns. The expansion of subtype C infection corroborates surveillance of HIV-1 diversity in this region. PMID- 22317909 TI - RP1 and retinitis pigmentosa: report of novel mutations and insight into mutational mechanism. AB - BACKGROUND/AIM: Retinitis pigmentosa (RP) is the commonest form of retinal dystrophy and is usually inherited as a monogenic trait but with remarkable genetic heterogeneity. RP1 is one of the earliest identified disease genes in RP with mutations in this gene known to act both recessively and dominantly although the mutational mechanism remains unclear. This study is part of our ongoing effort to characterise RP in Saudi Arabia at the molecular level. METHODS: Homozygosity mapping and candidate gene analysis. RESULTS: The authors have identified four novel mutations, all recessive, in a number of families with a typical RP phenotype. CONCLUSION: The distribution of these novel and previously reported RP1 mutations makes it challenging to describe a unifying mutational mechanism for dominant versus recessive RP1-related RP. PMID- 22317910 TI - Corneal chalcosis following blast injury. PMID- 22317911 TI - Test--retest variability of Randot stereoacuity measures gathered in an unselected sample of UK primary school children. AB - AIM: To determine the test-retest reliability of the Randot stereoacuity test when used as part of vision screening in schools. METHODS: Randot stereoacuity (graded-circles) and logMAR visual acuity measures were gathered in an unselected sample of 139 children (aged 4-12, mean 8.1+/-2.1 years) in two schools. Randot testing was repeated on two occasions (average interval between successive tests 8 days, range: 1-21 days). Three Randot scores were obtained in 97.8% of children. RESULTS: Randot stereoacuity improved by an average of one plate (ie, one test level) on repeat testing but was little changed when tested on the third occasion. Within-subject variability was up to three test levels on repeat testing. When stereoacuity was categorised as 'fine', 'intermediate' or 'coarse', the greatest variability was found among younger children who exhibited 'intermediate' or 'coarse'/nil stereopsis on initial testing. Whereas 90.8% of children with 'fine' stereopsis (<=50 arc-seconds) on the first test exhibited 'fine' stereopsis on both subsequent tests, only ~16% of children with 'intermediate' (>50 but <=140 arc-seconds) or 'coarse'/nil (>=200 arc-seconds) stereoacuity on initial testing exhibited stable test results on repeat testing. CONCLUSIONS: Children exhibiting abnormal stereoacuity on initial testing are very likely to exhibit a normal result when retested. The value of a single, abnormal Randot graded-circles stereoacuity measure from school screening is therefore questionable. PMID- 22317912 TI - Blindness and visual impairment due to uncorrected refractive error in sub Saharan Africa: review of recent population-based studies. AB - AIM: The authors aimed to review published data on uncorrected refractive error (URE) as a cause of blindness and visual impairment in adults aged >=40 years in sub-Saharan Africa (SSA). METHODS: Data were extracted from population-based prevalence surveys measuring presenting visual acuity (PVA). Results from 11 surveys performed in 10 countries in SSA, encompassing 39,458 people aged >=40 years and older, are presented. RESULTS: The prevalence of blindness (PVA<3/60 in better eye) ranged from 1.1% in an urban district of Cameroon to 7.9% in a rural district in Ethiopia. More than half of studies (6/11) reported no blindness due to URE. The proportion of moderate visual impairment (PVA <=6/60 and >6/18) due to URE ranged from 12.3% to 57.1%. Excluding two studies that included uncorrected aphakia as part of URE, the highest proportion of blindness and severe visual impairment due to uncorrected aphakia was found in Gambia (15.2%) and Nigeria (15.8%), respectively. CONCLUSION: Although URE is a leading cause of visual impairment, it does not represent a major cause of blindness in SSA. PMID- 22317913 TI - Cionni ring and in-the-bag intraocular lens implantation for subluxated lenses: a prospective case series. AB - PURPOSE: To report the intraoperative performance and postoperative outcomes of the Cionni-modified capsule tension ring (CTR) implantation in eyes with subluxated lenses. DESIGN: Prospective, observational case series. METHODS: This study was carried out at Iladevi Cataract & IOL Research Centre, Ahmedabad, India. The study population comprised 41 eyes with subluxated lenses that underwent lens extraction, capsular bag fixation with modified CTR, and in-the bag single-piece AcrySof intraocular lens (IOL) implantation. Main outcome measures were intraoperative performance and postoperative best-corrected visual acuity (BCVA), IOL centration, and complications. RESULTS: The mean age was 29.46 +/- 16.16 years (3-68 years). Mean extent of subluxation was 6.1 +/- 1.0 clock hours. Preoperatively, vitreous was detected in the anterior chambers of 5 eyes (12.2%). Two-port anterior chamber vitrectomy was performed in 2 eyes. Mean follow-up was 45.8 +/- 2.9 months. Mean preoperative BCVA was 0.66 +/- 0.22 logMAR (35 eyes). Mean postoperative BCVA at final follow-up was 0.33 +/- 0.21 logMAR (41 eyes) (P < .001). BCVA improved in 35 eyes (85.4%) at the last follow up. In 3 eyes (7.3%) IOL decentration was noted and repositioning was required in 2 eyes. Posterior capsule opacification developed in 14 eyes (34.2%); 12 eyes (29.3%) required Nd:YAG capsulotomy. Other complications included cystoid macular edema in 1 eye (2.4%), posterior synechiae in 1 eye (2.4%), and retinal detachment in 1 eye (2.4%). CONCLUSION: In-the-bag implantation of a Cionni modified CTR with IOL appears to be a safe option in eyes with subluxated cataract, ensuring a stable IOL with few complications. PMID- 22317914 TI - Combining structural and functional measurements to improve estimates of rates of glaucomatous progression. AB - PURPOSE: To evaluate whether a combination of topographic optic disc measurements and visual field data may improve the estimation of rates of structural and functional progression in glaucoma and the prediction of future outcomes in the disease. DESIGN: Observational cohort study. METHODS: The study included 242 eyes of 179 glaucoma patients followed for an average of 6.4 +/- 1.1 years. Subjects were longitudinally monitored with standard automated perimetry (SAP) and confocal scanning laser ophthalmoscopy (CSLO). Slopes of functional and structural change over time were evaluated by the parameters mean deviation (MD) and rim area, respectively. For each eye, the follow-up time was divided into 2 equal periods: the first half was used to obtain the slopes of change and the second period was used to test the predictions. Slopes of change were calculated using 2 methods, the conventional approach of ordinary least squares linear regression and a Bayesian joint regression model integrating structural and functional information. The mean square error (MSE) of the predictions was used to compare the predictive performance of the different methods. RESULTS: Bayesian slopes were more accurate than those obtained by the ordinary least squares method in predicting future MD (MSE: 5.13 vs 11.2, respectively; P < .001) and rim area values (MSE: 0.016 vs 0.027, respectively; P < .01). CONCLUSION: A Bayesian joint regression model combining structure and function resulted in more accurate and precise estimates of slopes of change compared to the conventional method of ordinary least squares linear regression. PMID- 22317915 TI - The effect of corneal wavefront aberrations on corneal pseudoaccommodation. AB - PURPOSE: To determine the effect on corneal pseudoaccommodation of anterior corneal wavefront aberrations in normal corneas and corneas with prior myopic or hyperopic photorefractive keratectomy (PRK) or laser-assisted in situ keratomileusis (LASIK). DESIGN: Theoretical study. METHODS: In 220 normal eyes, 102 myopic-PRK eyes, and 106 hyperopic-LASIK/PRK eyes, anterior corneal higher order aberrations (HOAs, third to sixth order, 6- and 4-mm pupils) were computed from the Atlas corneal elevation data using the VOL-CT program. Using the ZernikeTool, corneal optical image quality was evaluated by the polychromatic modulation transfer function with Stiles-Crawford effect. Defocus from -3.0 diopters (D) to +3.0 D was added to corneal HOAs, and depth of focus was defined as the ranges over which the polychromatic modulation transfer function maintains 80% of the peak value (DOF80) and 50% of the peak value (DOF50). The depth of focus values between groups were compared, stepwise multiple regression was used to assess if any Zernike terms significantly contributed to the depth of focus, and correlation analysis was performed to evaluate the correlation between depth of focus and corneal HOAs. RESULTS: The depth of focus varied widely between corneas, especially in corneas with prior hyperopic-LASIK/PRK. For 6-mm pupil, mean depth of focus values in myopic-PRK and hyperopic-LASIK/PRK corneas were significantly greater than those for normal corneas, and for 4-mm pupil, depth of focus values in hyperopic-LASIK/PRK corneas were greater than those in normal and myopic-PRK corneas. Zernike terms significantly contributing to both DOF80 and DOF50 were fourth- and sixth-order spherical aberration and fourth- and sixth order astigmatism in normal corneas, third-order vertical coma and fourth-order tetrafoil in myopic-PRK corneas, and third-order vertical coma and fourth-order astigmatism in hyperopic-LASIK/PRK corneas. Depth of focus had weak to moderate positive correlation with HOAs (Pearson correlation coefficient r ranged from 0.300 to 0.583). CONCLUSION: These theoretical calculations suggest that certain corneal wavefront aberrations affect corneal pseudoaccommodation. To predict corneal pseudoaccommodation, the most important Zernike term is spherical aberration in normal eyes and coma in eyes with prior laser corneal surgery. PMID- 22317916 TI - Proteome folding and aggregation. AB - The description of protein folding at the proteome level requires further principles in addition to those that govern this phenomenon for individual molecules. An important aspect of the increased complexity of the folding process in the cellular environment is that proteins tend to be metastable against aggregation, as they are often expressed at levels at which they are poorly soluble. The maintenance of the solubility of the proteome requires the coordinated intervention of a range of quality control mechanisms, which include molecular chaperones, trafficking and degradation pathways, post-translational modifications and transcriptional and translational control. As these regulatory mechanisms should always be active to keep proteins in their soluble state, their impairment upon ageing or environmental stress can lead to the disruption of protein homeostasis resulting in uncontrolled widespread aggregation and disease. PMID- 22317917 TI - Effect of pressure on itinerant magnetism and spin disorder in cubic FeGe. AB - The results of ab initio calculations of the pressure dependence of Fe magnetism in cubic FeGe are presented. We find that when the pressure-volume scale is set by means of generalized gradient approximation total energies and magnetism is described by means of the local density approximation, the critical pressure at which the magnetic phase transition occurs is estimated at ~18 GPa, which is in good agreement with experiments. Using the disordered local moment method we find a localized to itinerant model cross-over of Fe magnetism in cubic FeGe, as a function of volume. Moreover, our calculations also suggest subtle signatures of longitudinal spin fluctuations in cubic FeGe, and that the stiffness parameter softens with increasing pressure. We associate the retention of metallicity in FeGe under pressure with the spin-disorder scattering. The effect of spin-orbit coupling on the electronic structure is also discussed. PMID- 22317918 TI - The B cell receptor-induced calcium flux involves a calcium mediated positive feedback loop. AB - The B cell receptor (BCR)-elicited calcium flux results in activation of mature B cells. We have recently shown that the adaptor protein Swiprosin-1/EFhd2 (EFhd2) amplifies the BCR-induced calcium flux in B cell lines. EFhd2 is a calcium binding adaptor protein with two predicted EF-hands. Here we asked whether these domains are functional and control its function. Using a blot-overlay assay with radioactive calcium we show that both EF-hands of EFhd2 have an intrinsic capacity to bind calcium. Equilibrium centrifugation confirmed that EFhd2 binds 2 calcium ions, with an apparent Kd of 110 MUM. Point mutations revealed that the conserved residues E116 and E152, which reside in the canonical calcium binding loop in EF-hands 1 and 2, are essential for calcium binding by EFhd2. These mutations as well as deletion of the EF-hands, in particular EF-hand 1, abolished the ability of EFhd2 to restore BCR-induced calcium signaling in EFhd2-deficient WEHI231 cells. N-terminal deletions, but not C-terminal deletions, acted similarly. Thus, the N-terminal part of EFhd2 as well as calcium binding to its EF-hands control the intracellular calcium concentration in response to BCR stimulation in WEHI231 cells. Hence, EFhd2 regulates the BCR-elicited calcium flux through a calcium-dependent positive feedback mechanism in WEHI231 cells. PMID- 22317919 TI - Calcium channel types contributing to chromaffin cell excitability, exocytosis and endocytosis. AB - Voltage gated Ca(2+) channels are effective voltage sensors of plasma membrane which convert cell depolarizations into Ca(2+) signaling. The chromaffin cells of the adrenal medulla utilize a large number of Ca(2+) channel types to drive the Ca(2+)-dependent release of catecholamines into blood circulation, during normal or stress-induced conditions. Some of the Ca(2+) channels expressed in chromaffin cells (L, N, P/Q, R and T), however, do not control only vesicle fusion and catecholamine release. They also subserve a variety of key activities which are vital for the physiological and pathological functioning of the cell, like: (i) shaping the action potentials of electrical oscillations driven either spontaneously or by ACh stimulation, (ii) controlling the action potential frequency of tonic or bursts firing, (iii) regulating the compensatory and excess endocytosis following robust exocytosis and (iv) driving the remodeling of Ca(2+) signaling which occurs during stressors stimulation. Here, we will briefly review the well-established properties of voltage-gated Ca(2+) channels accumulated over the past three decades focusing on the most recent discoveries on the role that L (Cav1.2, Cav1.3) and T-type (Cav3.2) channels play in the control of excitability, exocytosis and endocytosis of chromaffin cells in normal and stress mimicking conditions. PMID- 22317920 TI - An "inordinate fondness for transporters" explained? AB - An often-asked question is, Why are there so many different transporters in a cell to take up a particular substrate? At least part of the answer comes from work on the possible competitive advantage of dual-transporter systems. In such systems, low-affinity transporters function when a nutrient is plentiful in the environment, and the abundance of high-affinity transporters is increased when that nutrient becomes scarce. A dual-transporter system enabled a long "preparation phase" to occur during which cells induce gene expression as they become increasingly starved. Surprisingly, the preparation phase is important not for growth under low-nutrient conditions but rather for fluctuating nutrient amounts as commonly occurs in nature. Thus, this creative study provides a previously unconsidered explanation for the abundance of dual-transporter systems in biology. PMID- 22317921 TI - Protein kinase CK2 triggers cytosolic zinc signaling pathways by phosphorylation of zinc channel ZIP7. AB - The transition element zinc, which has recently been identified as an intracellular second messenger, has been implicated in various signaling pathways, including those leading to cell proliferation. Zinc channels of the ZIP (ZRT1- and IRT1-like protein) family [also known as solute carrier family 39A (SLC39A)] transiently increase the cytosolic free zinc (Zn(2+)) concentration in response to extracellular signals. We show that phosphorylation of evolutionarily conserved residues in endoplasmic reticulum zinc channel ZIP7 is associated with the gated release of Zn(2+) from intracellular stores, leading to activation of tyrosine kinases and the phosphorylation of AKT and extracellular signal regulated kinases 1 and 2. Through pharmacological manipulation, proximity ligation assay, and mutagenesis, we identified protein kinase CK2 as the kinase responsible for ZIP7 activation. Together, the present results show that transition element channels in eukaryotes can be activated posttranslationally by phosphorylation, as part of a cell signaling cascade. Our study links the regulated release of zinc from intracellular stores to phosphorylation of kinases involved in proliferative responses and cell migration, suggesting a functional role for ZIP7 and zinc signals in these events. The connection with proliferation and migration, as well as the activation of ZIP7 by CK2, a kinase that is antiapoptotic and promotes cell division, suggests that ZIP7 may provide a target for anticancer drug development. PMID- 22317922 TI - PTEN directly activates the actin depolymerization factor cofilin-1 during PGE2 mediated inhibition of phagocytosis of fungi. AB - Macrophage ingestion of the yeast Candida albicans requires its recognition by multiple receptors and the activation of diverse signaling programs. Synthesis of the lipid mediator prostaglandin E(2) (PGE(2)) and generation of cyclic adenosine monophosphate (cAMP) also accompany this process. Here, we characterized the mechanisms underlying PGE(2)-mediated inhibition of phagocytosis and filamentous actin (F-actin) polymerization in response to ingestion of C. albicans by alveolar macrophages. PGE(2) suppressed phagocytosis and F-actin formation through the PGE(2) receptors EP2 and EP4, cAMP, and activation of types I and II protein kinase A. Dephosphorylation and activation of the actin depolymerizing factor cofilin-1 were necessary for these inhibitory effects of PGE(2). PGE(2) dependent activation of cofilin-1 was mediated by the protein phosphatase activity of PTEN (phosphatase and tensin homolog deleted on chromosome 10), with which it directly associated. Because enhanced production of PGE(2) accompanies many immunosuppressed states, the PTEN-dependent pathway described here may contribute to impaired antifungal defenses. PMID- 22317923 TI - In utero and lactational exposure to low-dose genistein-vinclozolin mixture affects the development and growth factor mRNA expression of the submandibular salivary gland in immature female rats. AB - It has been suggested that hormonally controlled submandibular salivary gland (SSG) development and secretions may be affected by endocrine disruptor compounds. We investigated the effects of oral gestation-lactation exposure to 1 mg/kg body weight daily dose of the estrogenic soy-isoflavone genistein and/or the anti-androgenic food contaminant vinclozolin in female rats. The SSGs of female offspring were collected at postnatal day 35 to study gland morphogenesis and mRNA expression of sex-hormone receptors and endocrine growth factors as sex dependent biomarkers. Because of high expression in neonatal SSG, mRNA expression of transforming growth factor alpha was also studied. Exposure to genistein, vinclozolin, or a genistein+vinclozolin mixture resulted in significantly lower numbers of striated ducts linked to an increase in their area and lower acinar proliferation (Ki-67-positive nuclei). Exposure to the mixture had the highest significant effects, which were particularly associated with repression of epidermal growth factor, nerve growth factor, and transforming growth factor alpha expression. In conclusion, early exposure to low doses of genistein and vinclozolin can affect glandular structure and endocrine gene mRNA expression in prepubertal SSG in female rats, and the effects are potentialized by the genistein+vinclozolin mixture. Our study provides the first evidence that SSG are targeted by both estrogenic and anti-androgenic disrupting compounds and are more sensitive to mixtures. PMID- 22317924 TI - Immunohistochemical features of 3,3',4,4'-tetrachloroazobenzene-induced rat gingival lesions. AB - Gingival lesions of squamous hyperplasia, cystic keratinizing hyperplasia (CKH), and squamous cell carcinoma (SCC) can be induced in rats treated by chronic gavage with 10-100 mg/kg 3,3',4,4'-tetrachloroazobenzene. We evaluated gingival squamous hyperplasia (GSH), CKH, and SCC for the immunohistochemical pattern of expression of carcinogenesis-associated markers. The 3 types of lesions and controls were stained with proliferation markers (proliferating cell nuclear antigen [PCNA] and cyclin-D1), tumor-suppressor markers (beta-catenin and mammary serine protease inhibitor [maspin]) and stroma-related markers (alpha-smooth muscle actin [SMA] and osteonectin/SPARC). The lesions had common immunohistochemical characteristics that differed in their expression patterns among the various diagnoses. PCNA and cyclin-D1 expression was higher in GSH, CKH, and SCC than in controls. The normal membranous expression of beta-catenin was lower in GSH, and almost absent in CKH and SCC. Maspin expression was similar in GSH and controls, whereas both CKH and SCC showed decreased expression. SMA and/or osteonectin/SPARC were seen in stromal cells in CKH and SCC. Collectively, there appears to be a progression from hyperplastic and cystic lesions toward malignancy based on the morphological changes, supported by the expression of carcinogenesis-associated proteins. The exact sequence of events leading to SCC remains to be defined in a time-dependent manner. PMID- 22317925 TI - Technical guide for nervous system sampling of the cynomolgus monkey for general toxicity studies. AB - For general toxicity studies, a technique was designed to consistently sample the most important neuroanatomic regions of the brain, spinal cord, and peripheral nerve of cynomolgus monkeys using a limited number of blocks and slides. Using the most rostral portion of the pons as a landmark, the entire fixed brain was cut dorsoventrally into cross-sectional slabs 4 mm in thickness. For microscopic evaluation, six blocks of the brain at the levels of the frontal pole, anterior commissure, rostral thalamus, caudal thalamus, middle cerebellum with brainstem, and occipital lobe were trimmed to fit in standard tissue cassettes. Cross- and oblique sections of the spinal cord including the dorsal root ganglion and dorsal and ventral nerve roots were obtained at the levels of C1-C4, T10-T12, and L1-L4. Cross- and longitudinal sections of the sciatic nerve were also obtained. This technique offers a consistent and reliable method to routinely sample most of the important regions of the central and peripheral nervous system of monkeys using ten blocks. This method is readily adaptable to other species of nonhuman primates, dogs, and minipigs and can be quickly learned by the technicians performing the trimming procedures. PMID- 22317926 TI - Starting 2012: Sod2, DGAT1, p53, SPARC, QTL and reprogramming in aging. PMID- 22317927 TI - Hypertension and acute myocardial infarction: an overview. AB - History of hypertension is a frequent finding in patients with acute myocardial infarction (AMI) and its recurring association with female sex, diabetes, older age, less frequent smoking and more frequent vascular comorbidities composes a risk profile quite distinctive from the normotensive ischemic counterpart.Antecedent hypertension associates with higher rates of death and morbid events both during the early and long-term course of AMI, particularly if complicated by left ventricular dysfunction and/or congestive heart failure. Renin-angiotensin-aldosterone system blockade, through either angiotensin converting enzyme inhibition, angiotensin II receptor blockade or aldosterone antagonism, exerts particular benefits in that high-risk hypertensive subgroup.In contrast to the negative implications carried by antecedent hypertension, higher systolic pressure at the onset of chest pain associates with lower mortality within 1 year from coronary occlusion, whereas increased blood pressure recorded after hemodynamic stabilization from the acute ischemic event bears inconsistent relationships with recurring coronary events in the long-term follow-up.Whether antihypertensive treatment in post-AMI hypertensive patients prevents ischemic relapses is uncertain. As a matter of fact, excessive diastolic pressure drops may jeopardize coronary perfusion and predispose to new acute coronary events, although the precise cause-effect mechanisms underlying this phenomenon need further evaluation. PMID- 22317928 TI - Anterior myocardial infarction in a patient with dual left anterior descending coronary artery. AB - The incidence of dual left anterior descending coronary artery (LAD) in normal hearts has been reported to range from 0.13 to 1%. Type IV dual LAD differs from the other three types in the origination of the long LAD from the right coronary sinus. We present a case of type IV dual LAD in a patient with anterior myocardial infarction related to the short LAD. PMID- 22317929 TI - Re-operation for failed gastro-esophageal fundoplication. What results to expect? AB - The aim of this study is to evaluate short and medium term results of re operation for failed fundoplication in a retrospective monocentric cohort of 47 patients. PATIENTS AND METHODS: Between 1995 and 2011, 595 patients underwent a laparoscopic primary fundoplication (PFP) for gastroesophageal reflux disease (GERD). During the same period, 47 patients required a re-operative fundoplication (RFP). In 11 patients, the original wrap had herniated into the thorax. All these revisions consisted of a complete takedown of the original wrap before constructing a tension-free wrap using a standardized technique. Patients with a follow-up of at least 2 years were matched to patients who had been operated only once to assess satisfaction and quality of life. RESULTS: Short term: All patients were operated by laparoscopy with no conversion. There was no mortality. Two postoperative complications necessitating re-operation were observed (morbidity 4.3%): one complete aphagia and one gastric perforation. Long term: 29 re-operated patients with a follow-up of at least 2 years (mean: 4,5 years) (Group RFP) were compared to a matched group of 29 patients operated only once (Group PFP). These groups were comparable in age, sex ratio, BMI and follow up. In both groups, all patients were operated by laparoscopy without conversion. Morbidity was 3.5% in the RFP group, none in the PFP group. There was no mortality in either group. The length of stay and operative time were significantly higher in the RFP group (4.6 vs. 2.6 days, p<0.05). Two RFP patients (5%) required re-operation at three and seven months vs. none in the PFP group. The long-term satisfaction was comparable in the two groups (78% vs. 85%, p=NS). Quality of life assessed by the GIQLI was significantly better in the PFP group (104 vs. 84, p<0.05). CONCLUSION: Re-do fundoplication is a safe procedure and is feasible by laparoscopy. In the long-term, patient satisfaction is comparable to primary intervention with, however, a slightly poorer quality of life. PMID- 22317930 TI - Central pancreatectomy: comparison of results according to the type of anastomosis. AB - INTRODUCTION: The mild pancreatic tumors are more and more treated by central pancreatectomy (CP) in alternative with the widened pancreatectomies. Indeed, their morbidity is lesser but they are however burdened by a rate of important postoperative fistulas. The purpose of our study is to compare pancreatico jejunal anastomosis and pancreatico-gastric anastomosis. METHODS: This work was realized in a bicentric retrospective way. Twenty-five CP were included and classified according to two groups according to the pancreatic anastomosis (group 1 for pancreatico-jejunal anastomosis and group 2 for the pancreatico-gastric anastomosis). CP was realized according to a protocol standardized in both centers and the complications were classified according to the classification of Clavien and Dindo and the fistulas according to the classification of Bassi. RESULTS: Both groups were comparable. The duration operating and the blood losses were equivalent in both groups. There was a significant difference (P=0,014) as regards the rate of fistula. The pancreatico-gastric anastomosis complicated more often of a low-grade fistula. However, in both groups, the treatment was mainly medical. Our results were comparable with those found in the literature and confirmed the advantages of the CP with regard to the cephalic duodeno pancreatectomy (DPC) or to the distal pancreatectomy (DP). However, in the literature, a meta-analysis did not report difference between both types of anastomosis but this one concerned only the DPC. CONCLUSIONS: This work showed a less important incidence of low-grade fistula after pancreatico-jejunal anastomosis in the fall of a PM. This result should be confirmed by a later study on a more important sample of PM. PMID- 22317931 TI - Repeat hepatectomy for liver metastases from colorectal primary cancer: a review of the literature. AB - INTRODUCTION: After hepatectomy for metastases from colorectal cancer (CRC), approximately 50% to 70% of patients develop recurrent hepatic metastases. This recurrence is limited to the liver in about one-third of cases. The purpose of this study is to report a comprehensive review of the literature concerning the results of repeat hepatectomy for recurrent liver metastases from CRC. METHODS: An electronic literature search was conducted to identify all medical articles published concerning repeat hepatectomy for liver metastases of colorectal origin during the period January 1990 to December 2010. RESULTS: After a second hepatectomy, the mean mortality was 1.4% and the mean morbidity rate was 21.3%. The 5-year survival ranged from 16% to 55%. After a third or fourth hepatectomy, the mean mortality rate was 0% and the mean morbidity rate was 24.5%. After a third hepatectomy, the 5-year survival ranged from 23.8% to 37.9%. After a fourth hepatectomy, the 5-year survival was 9.3% to 36%. CONCLUSION: Repeat hepatectomy seems justified, since it may result in prolonged survival with acceptable rates of morbidity and mortality, results similar to those seen after initial hepatectomy. PMID- 22317932 TI - Infections in acute older stroke inpatients undergoing rehabilitation. AB - OBJECTIVE: The present study compares the incidence of various infections among patients in acute and rehabilitation wards and examines the risk factors and pathogens involved in rehabilitation ward infections. DESIGN: The study included 341 acute stroke patients (age, >=65 yrs). The assessment of risk factors was done by comparison of patients with or without infection, urinary tract infection, and pneumonia. Possible precipitating factors in each comparison were included in the statistical analysis. RESULTS: Ninety-five (27.9%) patients experienced infections, and the most common type in the rehabilitation ward was urinary tract infection. The frequency of incidence of pneumonia in the rehabilitation ward (6.7%) was significantly lower than in the acute ward (23.8%) (P < 0.001). Patients with infection had a longer rehabilitation ward stay compared with those without infection (30.9 vs. 18.8 days, P = 0.002). A postvoid residual urine volume greater than 50 ml (odds ratio, 2.314; 95% CI, 1.204-4.448, P = 0.012) was found to be the most important risk factor for infection. CONCLUSIONS: Infection may prolong the length of stay in acute stroke patients in a rehabilitation ward. The present study provides important information for clinicians to help identify risk factors for infection. PMID- 22317933 TI - Medical rehabilitation of people with spinal cord injury during 40 years of academic physiatric practice. AB - There are many different paths that lead to an academic physiatric career and a lifelong interest in spinal cord injury (SCI) medicine. It is unfortunate that after decades of cellular-based research in multiple laboratories, there are still no interventions available that can reverse the neurologic loss that follows SCI. In contrast, medical rehabilitation research during the last 40 yrs has led to remarkable improvements in the lives of persons with SCI as evident in their increased life expectancy, shorter hospitalizations, fewer rehospitalizations, and more effective treatments for male sexual dysfunction and fertility, as well as spasticity, heterotrophic ossification, and neuropathic pain. Application of modern technology has improved the mobility of persons with SCI with better designed wheelchairs, decreased their dependency on others, facilitated their access to information, made communication and community integration easier, and so on. Although deaths related to urinary tract complications are now rare, better methods of managing the neurogenic bladder are still needed. Furthermore, better management methods are also needed for the neurogenic bowel, SCI pain, and osteoporosis of the paralyzed limbs. Even with proper prophylaxis, deep vein thrombosis and pulmonary embolism are still common, and clinicians have paid too little attention to reducing the risk for persons with SCI of developing obesity, diabetes mellitus, and cardiovascular disease. These challenges need to be met by medical rehabilitation research, by advocating for insurance policies that support the healthcare needs of persons with SCI, and by developing comprehensive disability policies, all with the support and leadership of academic physiatrists. PMID- 22317934 TI - Unreduced congenital dislocation of both hips in an adult woman. PMID- 22317935 TI - RE: Electrodiagnosis in cancer treatment and rehabilitation. PMID- 22317936 TI - RE: Inpatient rehabilitation improved functional status in asthenic patients with solid and hematologic malignancies. PMID- 22317937 TI - RE: Underlying pathology and associated factors of hemiplegic shoulder pain. PMID- 22317938 TI - RE: Cervical cord injury after massage. PMID- 22317940 TI - Re: Ulnar neuropathy at the elbow in diabetes. PMID- 22317942 TI - Re: Assessing weakness in patients with ulnar neuropathy: comparison between a custom hand muscle dynamometer and a pinch dynamometer. PMID- 22317944 TI - Efficacy of vitamins C, E, and their combination for treatment of restless legs syndrome in hemodialysis patients: a randomized, double-blind, placebo-controlled trial. AB - BACKGROUND: Restless legs syndrome (RLS) is a common disorder in hemodialysis patients that leads to insomnia and impaired quality of life. Because high oxidative stress has been implicated in the pathogenesis of RLS, we sought to evaluate the efficacy of vitamins C and E and their combination in reducing the severity of RLS symptoms in hemodialysis patients in this randomized, double blind, placebo-controlled, four-arm parallel trial. METHODS: Sixty stable hemodialysis patients who had all four diagnostic criteria for RLS developed by the International Restless Legs Syndrome Group with no acute illness or history of renal stone were randomly allocated to four fifteen-patient parallel groups to receive vitamin C (200 mg) and vitamin E (400 mg), vitamin C (200 mg) and placebo, vitamin E (400 mg) and placebo, and double placebo daily for eight weeks. International Restless Legs Scale (IRLS) scores were measured for all patients at baseline and at the end of treatment phase. The primary outcome was absolute change in IRLS sum score from baseline to the end of treatment phase. RESULTS: Means of IRLS sum score decreased significantly in the vitamins C and E (10.3 +/- 5.3, 95% CI: 7.4-13.3), vitamin C and placebo (10 +/- 3.5, 95% CI: 8.1 11.9), and vitamin E and placebo groups (10.1 +/- 6, 95% CI: 6.8-13.5) compared with the double placebo group (3.1 +/- 3, 95% CI: 1.5-4.8), (P<0.001); however, no differences were observed between these treatment groups. CONCLUSIONS: Vitamins C and E and their combination are safe and effective treatments for reducing the severity of RLS in hemodialysis patients over the short-term. PMID- 22317945 TI - Comparison of actigraphy and polysomnography to assess effects of zolpidem in a clinical research unit. AB - OBJECTIVE: This study sought to compare devices that use actigraphy for measuring sleep endpoints in the clinical research unit (CRU) and home environment. The abilities of polysomnography (PSG) and actigraphy monitors to detect drug effects in a CRU were also investigated. METHODS: Eleven healthy subjects were recruited and monitored with PSG for four consecutive nights in a CRU after receiving no treatment (night 1, N1), and then placebo or 5 mg day(-1) or 10 mg day(-1) zolpidem in a randomised, cross-over design. Subjects wore two devices that use actigraphy (a Respironics(r) Actiwatch(r) on the wrist and a BodyMedia(r) Sensewear(r) Armband on the upper-arm) on the non-dominant arm for five nights at home and four nights in the CRU during PSG. RESULTS: Wake after sleep onset (WASO) and total sleep time (TST) measured by PSG and estimates of WASO by the Actiwatch decreased significantly with 5mg but not 10mg of zolpidem versus placebo. Direct activity (counts/min) with the Actiwatch decreased in response to zolpidem (both 5 and 10 mg day(-1)) versus placebo. Armband recordings of direct activity were similar to the Actiwatch but not significantly different versus placebo. Both actigraphy device estimates of TST were approximately 1h longer in CRU versus home. Agreement between actigraphy estimates of TST and WASO and PSG values of TST and WASO were closer during nights with zolpidem treatment. CONCLUSIONS: PSG can detect the effects of zolpidem on sleep in a CRU setting. Actigraphy can provide useful assessment of sleep, but direct activity endpoints may be more effective than estimates of TST and WASO. PMID- 22317946 TI - World Congress of Epidemiology 2011: themes and highlights. AB - Modern-day epidemiologists are confronted with huge changes, such as the rise in the global population due to reduced mortality, migration within and across countries, massive shifts in economic standing and lifestyles, and environmental degradation. With over 1000 posters, more than 100 oral presentations, 16 workshops, four lunchtime symposia, many exhibitions and immeasurable discussions, the task of capturing all highlights of the International Epidemiology Association (IEA) World Congress of Epidemiology 2011 is impossible, but this article has provided a sample. Many presenters showed that the challenges facing global health are complex, changing and in demand of measurement, and they demonstrated the central role of epidemiology. The cutting edge methodologies theme promised the emergence of a more transparent, better balanced, but also more critical approach to dealing with bias. Preceding the United Nations high-level meeting on non-communicable diseases (New York, 19th 20th September 2011), the Congress's chronic diseases stream was especially timely. The neglected conditions theme illustrated inspiring work battling against apathy, inertia and ignorance; perhaps the special challenge of the 'neglected conditions epidemiologist'. Translating epidemiology's insights into effective policies and programmes to prevent diseases or reduce their impact is not easy. Speakers highlighted the common failure of epidemiologists to contribute actively to improving the health of the populations they serve, especially the poor and disadvantaged, but also provided many examples where they had done so. The 'other' theme ensured that important studies were not lost from the programme just because they did not fit easily into the specific themes. The studies focused on identified risk factors throughout the life course. A variety of methods were used to identify factors that altered the rate of birth, disease and death. Ongoing epidemiology is not only broad but is also deep, and ever more so as collaborative pooling of expertise, data, populations and ideas has emerged, accelerated by modern-day communication technologies. Epidemiology, and epidemiologists, seem poised for tomorrow's world. PMID- 22317947 TI - Complications after flexor tendon repair: a systematic review and meta-analysis. AB - PURPOSE: Although outcomes after flexor tendon repair have reportedly improved with modern treatment, complications are common. The purpose of this study was to determine the incidence of these complications and the potential contributory factors within the published literature. METHODS: We performed a systematic review of the available literature to identify publications in which patients with flexor tendon ruptures were surgically treated. We extracted demographics, zone of injury, core suture technique (only modified Kessler or a combination of techniques), use of epitendinous suture, and date of publication (before or after January 1, 2000). We excluded articles if they did not report information on reoperation, rupture, or adhesions. We used unadjusted pooled meta-analysis to report the incidence of complications, and meta-regression to describe the potential contributory factors for each complication while controlling for age, gender, and zone of injury. RESULTS: Unadjusted meta-analysis revealed rates of re-operation of 6%, rupture of 4%, and adhesions of 4%. Meta-regression analysis of 29 studies showed that core suture technique or use of an epitendinous suture does not influence rupture. However, the presence of an epitendinous suture decreases re-operation by 84%. Adhesion development is 57% lower when the modified Kessler technique is used. The incidence of complications did not vary with publication date. CONCLUSIONS: The published literature supports use of the modified Kessler repair technique with an epitendinous suture to minimize complications. Although complication rates are low, our data suggest that there has been no definitive improvement in reported complications before and after 2000. PMID- 22317948 TI - Disparity in the management of Graves' disease observed at an urban county hospital: a decade-long experience. AB - BACKGROUND: The objective of this study was to determine whether health care disparities exist in management of Graves' disease. METHODS: Patients treated for Graves' disease from 1999 to 2009 were divided into medical and surgical treatment groups. A comparative analysis of age, sex, race, health insurance, and income was completed. Address and/or zip code were geocoded and median income was determined from census data. RESULTS: A total of 634 patients were treated for Graves' disease; 535 (84%) medically and 99 (16%) surgically. Mean age (40 +/- 15 vs 43 +/- 11 y), percentage of women (84% vs 91%), and racial distribution were similar in the 2 groups (P > .05). In the surgical group, median income was lower ($31,530 vs $34,404; P = .07) and 52% of patients were uninsured compared with 30% of patients treated medically (P < .0001). CONCLUSIONS: A disproportionate number of uninsured patients underwent thyroidectomy for Graves' disease. Social and economic factors may have a role in determining definitive therapy for Graves' disease. PMID- 22317949 TI - Author's reply: To PMID 21943947. PMID- 22317950 TI - Health-care sector and complementary medicine: practitioners' experiences of delivering acupuncture in the public and private sectors. AB - AIM: The aim was to identify similarities and differences between private practice and the National Health Service (NHS) in practitioners' experiences of delivering acupuncture to treat pain. We wished to identify differences that could affect patients' experiences and inform our understanding of how trials conducted in private clinics relate to NHS clinical practice. BACKGROUND: Acupuncture is commonly used in primary care for lower back pain and is recommended in the National Institute for Health and Clinical Excellence's guidelines. Previous studies have identified differences in patients' accounts of receiving acupuncture in the NHS and in the private sector. The major recent UK trial of acupuncture for back pain was conducted in the private sector. METHODS: Semi-structured qualitative interviews were conducted with 16 acupuncturists who had experience of working in the private sector (n = 7), in the NHS (n =3), and in both the sectors (n = 6). The interviews lasted between 24 and 77 min (median=49 min) and explored acupuncturists' experiences of treating patients in pain. Inductive thematic analysis was used to identify similarities and differences across private practice and the NHS. FINDINGS: The perceived effectiveness of acupuncture was described consistently and participants felt they did (or would) deliver acupuncture similarly in NHS and in private practice. In both the sectors, patients sought acupuncture as a last resort and acupuncturist-patient relationships were deemed important. Acupuncture availability differed across sectors: in the NHS it was constrained by Trust policies and in the private sector by patients' financial resources. There were greater opportunities for autonomous practice in the private sector and regulation was important for different reasons in each sector. In general, NHS practitioners had Western-focussed training and also used conventional medical techniques, whereas private practitioners were more likely to have Traditional Chinese training and to practise other complementary therapies in addition to acupuncture. Future studies should examine the impact of these differences on patients' clinical outcomes. PMID- 22317951 TI - Evaluation of paclitaxel/carboplatin in a dose dense or weekly regimen in 66 patients with recurrent or primary metastatic cervical cancer. AB - BACKGROUND AND AIMS: To evaluate paclitaxel/carboplatin in a dose dense (TCdd) and weekly (TCw) regimen in recurrent or primary metastatic cervical cancer. METHODS: Six courses of paclitaxel (90 mg/m(2)) and carboplatin (area under the curve (AUC) 4) were administered on d1, d8 q3 wks in TCdd. Eighteen courses of paclitaxel (60 mg/m(2)) and carboplatin (AUC 2.7) were administered weekly in TCw. Response rates were determined using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria. Toxicity was evaluated according to the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) Criteria. RESULTS: Sixty-six patients were included (44 TCdd and 22 TCw). TCdd and TCw were administered as first-line chemotherapy in 48% and 41%, second-line in 43% and 18%, and third/fourth-line in 9% and 41%, respectively. Response (confirmed or unconfirmed) was observed in 58% and 36% for TCdd and TCw, respectively. As first line, the response rates for TCdd and TCw were the same (55%). As second or more line, the response rates for TCdd and TCw were 61% and 29%, respectively. In patients, receiving TCdd as first-line systemic treatment, median overall survival (OS) and progression-free survival (PFS) was 10 and 5 months. As first line, the median OS for TCw also was 10 months (median PFS not reached). There was no statistical difference in PFS or OS between patients treated with TCw or TCdd. Grade 3-4 toxicity was mostly bone-marrow related and was more common with TCdd. Febrile neutropenia was observed in 0% and 12% of the patients treated with TCw and TCdd, respectively. CONCLUSIONS: Combination of paclitaxel and carboplatin in a dose dense regimen or weekly regimen resulted in favourable response rate and toxicity profile compared with cisplatin-based combination regimens. TCdd appears to be more toxic than TCw, but resulted in higher response rates than TCw in patients with recurrent metastatic cervical cancer who received prior chemotherapy. PMID- 22317952 TI - Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: results of the randomised GEFCAPI 02 trial. AB - PURPOSE: To compare the overall survival rates of good-prognosis carcinomas of an unknown primary site (CUPS) patients treated with cisplatin alone (C) or in combination with gemcitabine (CG). PATIENTS AND METHODS: Good prognosis was defined according to the GEFCAPI (Groupe d'Etude Francais des Carcinomes de site Primitif Inconnu) classification by PS (Performance Status) <= 1 and LDH (Lactate Deshydrogenase) within the normal range. Patients were randomly assigned to receive C or CG. Patients in the C arm received cisplatin 100 mg/m(2) repeated every 3 weeks. In the CG arm, chemotherapy consisted of gemcitabine 1250 mg/m(2) on days 1 and 8 and cisplatin 100 mg/m(2) IV on day 1, repeated every 3 weeks. The original plan was to accrue 192 patients in order to detect a 20% difference in overall survival. RESULTS: Fifty-two patients were enrolled (arm A: 25; arm B: 27). The trial was stopped early due to insufficient accrual. The median overall survival (OS) rate was 11 months [95% confidence interval: 9-20] and 8 months [95%CI: 6-12], in the CG arm and in the C arm, respectively. The 1-year survival rate was 46% [95%CI: 28-64] in the combination arm and 35% [95%CI: 19-56] in the C arm (log rank test: p=0.73). The median progression-free survival (PFS) rate was 5 [95%CI: 3-11] and 3 [95%CI: 1-8] months in the CG and in the C arm, respectively. The 1-year PFS rate was 29% [95%CI: 15-48] in the combination arm and 15% [95%CI: 5-35] in the C arm (log rank test: p=0.27). No toxic deaths occurred. Grade 3-4 neutropenia (63% versus 12%) and grade 3-4 thrombocytopenia (37% versus 4%) were more frequent in the CG arm than in the C arm. CONCLUSION: A non-significantly better outcome was observed with CG as compared to C in patients with CUP and a non-unfavourable prognosis. The toxicity profile of the combined arm was represented by haematologic toxicity with thrombocytopenia and leuconeutropenia. International collaboration is required to conduct phase III trials in patients with CUP. PMID- 22317953 TI - Increased incidence and survival for oesophageal cancer but not for gastric cardia cancer in the Netherlands. AB - INTRODUCTION: A worldwide increasing incidence is seen for oesophageal adenocarcinoma, but not for oesophageal squamous cell carcinoma (SCC) and gastric cardia adenocarcinoma. Purposes of the current study were to evaluate the changing incidence rates of oesophageal and gastric cardia cancer, and to assess survival trends. PATIENTS AND METHODS: Patients diagnosed with oesophageal adenocarcinoma (N=12,195) or SCC (N=9046), or gastric cardia adenocarcinoma (N=9900) between 1989 and 2008 in the Netherlands were included. Changes in European Standard Population (ESP) and relative survival over time were evaluated. RESULTS: Incidence rates for oesophageal adenocarcinoma increased in males (+7.5%, P<0.001) and females (+5.2%, P<0.001), while the incidence for oesophageal SCC remained stable in males (-0.2%, P=0.6) and slightly increased in females (+1.7%, P=0.001). The incidence for gastric cardia cancer decreased in males (-1.2%, P<0.006), and remained stable in females (-0.2%, P=0.7). Five-year survival for both M0 and M1 oesophageal carcinoma doubled over the last 20 years. No significant changes in survival were found for M0 and M1 gastric cardia carcinoma. DISCUSSION: In the Netherlands, a rising incidence is seen for oesophageal adenocarcinoma, but not for gastric cardia adenocarcinoma. This finding most likely reflects true changes in disease burden, rather than being the result of changes in diagnosis or classification. The increased survival for oesophageal carcinoma can be attributed to centralisation of surgery, and an increased use of multimodality therapy, factors hardly acknowledged for gastric cancer. PMID- 22317955 TI - In vivo confocal microscopy findings in central toxic keratopathy. AB - Central toxic keratopathy is an uncommon complication after laser in situ keratomileusis. We report the confocal microscopy findings in a case of central toxic keratopathy that confirm loss of keratocytes from the corneal stromal bed in the acute phase, with gradual repopulation over the following year. PMID- 22317956 TI - Effect of interaction of macroaberrations and scattered light on objective quality of vision in pseudophakic eyes with aspheric monofocal intraocular lenses. AB - PURPOSE: To assess the impact of wavefront ocular aberrations on objective vision quality and depth of focus in pseudophakic patients. SETTING: University Hospital Bretonneau of Tours, Francois Rabelais Medicine Faculty of Tours, France. DESIGN: Cohort study. METHODS: Consecutive eyes having implantation of an aspheric monofocal intraocular lens (IOL) (Acri.Smart) were studied. Aberrometry measurements were performed under mesopic conditions with a 6.0 mm pupil using a Wavescan aberrometer. Objective evaluation of optical vision quality was performed using the Optical Quality Analysis System II. The 3 measurements were the modulation transfer function values (MTF cutoff); objective depth of focus, which was computed as the focus range at which Strehl ratio did not fall below 50% of the maximum; and the objective scatter index. RESULTS: Fifty-four eyes (30 patients) were enrolled. Six months postoperatively, MTF cutoff values were increased with decreasing total ocular spherical aberration, ocular trefoil, and 2nd-order astigmatism (P<.05). Objective depth of focus was positively correlated with 2nd-order astigmatism (r(2) = 0.171, P<.001) and total spherical aberration (r(2) = 0.091, P=.028). Objective scatter was more beneficial for depth of focus, with a significantly positive correlation with this parameter (r(2) = 0.28, P=.002), than compromising of optical quality (no significant correlation with MTF measurements in same multiple regression analysis). CONCLUSION: Three ocular aberrations (2nd-order astigmatism, trefoil, spherical aberration) seemed to interact with objective contrast sensitivity and depth of focus, whereas residual spherical aberration exerted opposite effects on image quality in individual patients. PMID- 22317957 TI - Selective neutralization of APP-C99 with monoclonal antibodies reduces the production of Alzheimer's Abeta peptides. AB - The toxic amyloid-beta (Abeta) peptides involved in Alzheimer's disease (AD) are produced after processing of the amyloid precursor protein-C-terminal fragment APP-C99 by gamma-secretase. Thus, major therapeutic efforts have been focused on inhibiting the activity of this enzyme. However, preclinical and clinical trials testing gamma-secretase inhibitors revealed adverse side effects most likely attributed to impaired processing of the Notch-1 receptor, a gamma-secretase substrate critically involved in cell fate decisions. Here we report an innovative approach to selectively target the gamma-secretase-mediated processing of APP-C99 with monoclonal antibodies neutralizing this substrate. Generated by immunizing mice with natively folded APP-C99, these antibodies bound N- or C terminal accessible epitopes of this substrate, and decorated extracellular amyloid deposits in AD brain tissues. In cell-based assays, the same antibodies impaired APP-C99 processing by gamma-secretase, and reduced Abeta production. Furthermore, they significantly decreased brain Abeta levels in the APPPS1 mouse model of AD after intracerebroventricular injection. Together, our findings support APP-C99 substrate-targeting antibodies as new immunotherapeutic and Notch sparing agents to lower the levels of Abeta peptides implicated in AD. PMID- 22317958 TI - [Focal malignant peritoneal mesothelioma: a case report and review of the literature]. PMID- 22317959 TI - Influence of chronic administration of antidepressant drugs on mRNA for galanin, galanin receptors, and tyrosine hydroxylase in catecholaminergic and serotonergic cell-body regions in rat brain. AB - Activity of locus coeruleus (LC) neurons and release of the peptide galanin (GAL), which is colocalized with norepinephrine (NE) in LC neurons, has been implicated in depression and, conversely, in antidepressant action. The present study examined the influence of chronic administration (for 14days, via subcutaneously-implanted minipump) of antidepressant (AD) drugs representing three different classes (tricyclic [desipramine], selective serotonin reuptake inhibitor [SSRI] [paroxetine], and monoamine oxidase inhibitor [MAOI] [phenelzine]) on mRNA for GAL, GAL receptors (GalR1, GalR2, and GalR3), and tyrosine hydroxylase (TH), the rate-limiting enzyme for NE synthesis, in four brain regions--LC, A1/C1, dorsal raphe (DRN), and ventral tegmentum (VTA) of rats. Consistent with previous findings that chronic administration of AD drugs decreases activity of LC neurons, administration of AD drugs reduced mRNA for both GAL and TH in LC neurons. GAL and TH mRNA in LC neurons was highly correlated. AD drugs also reduced GAL and TH mRNA in A1/C1 and VTA but effects were smaller than in LC. The largest change in mRNA for GAL receptors produced by AD administration was to decrease mRNA for GalR2 receptors in the VTA region. Also, mRNA for GalR2 and GalR3 receptors was significantly (positively) correlated in all three predominantly catecholaminergic brain regions (LC, A1/C1, and VTA). Relative to these three brain regions, unique effects were seen in the DRN region, with the SSRI elevating GAL mRNA and with mRNA for GalR1 and GalR3 being highly correlated in this brain region. The findings show that chronic administration of AD drugs, which produces effective antidepressant action, results in changes in mRNA for GAL, GAL receptors, and TH in brain regions that likely participate in depression and antidepressant effects. PMID- 22317960 TI - Using a discrete choice experiment to elicit the demand for a nutritious food: willingness-to-pay for orange maize in rural Zambia. AB - Using a discrete choice experiment, this paper estimates the willingness to pay for biofortified orange maize in rural Zambia. The study design has five treatment arms, which enable an analysis of the impact of nutrition information, comparing the use of simulated radio versus community leaders in transmitting the nutrition message, on willingness to pay, and to account for possible novelty effects in the magnitude of premiums or discounts. The estimation strategy also takes into account lexicographic preferences of a subset of our respondents. The results suggest that (a) orange maize is not confused with yellow maize, and has the potential to compete with white maize in the absence of a nutrition campaign, (b) there is a premium for orange maize with nutrition information, and (c) different modes of nutritional message dissemination have the same impact on consumer acceptance. PMID- 22317961 TI - Oxnerella micra sp. n. (Oxnerellidae fam. n.), a tiny naked centrohelid, and the diversity and evolution of heliozoa. AB - We describe a new tiny naked centrohelid heliozoan, Oxnerella micra, and sequenced its 18S and 28S rRNA genes. Its extremely slender axopodia have prominent extrusomes and are normally stretched across the substratum like those of many tiny granofilosean Cercozoa. Phylogenetic analysis of 18S rDNA shows that Oxnerella does not branch within any of the six known centrohelid families but very deeply in the order Pterocystida, between Choanocystidae and Pterocystidae; therefore we place it in a new family, Oxnerellidae. Oxnerella arose from ancestors with siliceous scales by losing them; as independently did Heterophryidae and Marophryidae, which replaced them by organic spicules, and Chlamydaster that is not truly naked but retains a mucilage coat and nests extremely shallowly within Pterocystidae. 28S rDNA has a group I intron. Concatenated Bayesian 18S/28S rRNA phylogeny shows centrohelids weakly as sisters to the naked non-centrohelid heliozoan Microheliella maris (Microhelida: Heliozoa). The centrohelid Marophrys marina possesses an elongation factor alpha like (EFL) protein related to that of Polyplacocystis; Microheliella also has EFL. We also analysed Hsp90 and 18S rDNA sequences from 'Pinaciophora sp.' ATCC50355; they must be from a centrohelid, probably misidentified as Pinaciophora, the rDNA sequence branching deeply within Pterocystida. We reclassify two Polyplacocystis, Luffisphaera, Phaeodaria and Rotosphaerida. PMID- 22317962 TI - Asian Americans in leadership positions in academic surgery. AB - OBJECTIVE: To examine Asian American (Chinese, Japanese, Korean, Indian subcontinent, Southeast Asian, Philippine and South Pacific Islands, and Middle East) representation in national organizations and editorial boards important in US academic surgery. BACKGROUND: Asian Americans are overrepresented in academic departments of surgery relative to their demographic proportion of US population. Not examined is their involvement in leadership positions in the field. STUDY DESIGN: Current rosters were surveyed for surgeons with Asian American surnames with federally supported research, members of leading surgical specialty organizations, residency review committees for surgical specialties, surgical boards of the American Board of Medical Specialties, and editorial boards of leading surgical journals. RESULTS: Asian Americans are principal investigators in 18.9% of National Institutes of Health-supported grants in departments of surgery, and 7.7% of Society of University Surgeons and 3.2% of American Surgical Association memberships. Asian American representation on governing boards of professional organizations is only 2.3%, and none on the Boards of Regents of the American College of Surgeons, the various American Board of Medical Specialties surgical boards and councils, the residency review committees for surgery, and governing councils of 7 of 10 professional organizations. Of 302 US surgeons on the editorial boards of 5 leading surgical journals, 6 were Asian Americans (2.0%). CONCLUSIONS: Asian American academic surgeons are absent from the governing boards of surgical organizations and peer-reviewed surgical journals, a situation that mentorship and the development of effective social networks though an Asian American surgeons' association may correct. PMID- 22317963 TI - Publications, public policy, and scientific opportunity: a few personal thoughts. PMID- 22317964 TI - Interview with Michael Ristow. AB - Interview with Michael Ristow on his highly cited paper on his highly cited paper: Ristow M, Zarse K, Oberbach A, Kloting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Bl?her M. "Antioxidants prevent health-promoting effects of physical exercise in humans". Proc Natl Acad Sci U S A. 2009 May 26; 106(21):8665 70. By January 2012, "Antioxidants prevent health-promoting effects of physical exercise in humans" was cited more than 177 times. At the time of the interview it was 125 times so it is ranked as number 5 among 100,000 papers on aging in 2009. PMID- 22317965 TI - Banana as a relevant source of anthocyani(di)ns in European populations? PMID- 22317966 TI - Effect of omega-3 fatty acids supplementation on endothelial function: a meta analysis of randomized controlled trials. AB - OBJECTIVE: Inverse association was reported between omega-3 fatty acids (FAs) supplementation and the risk of cardiovascular disease. Identifying the effect of omega-3 FAs on endothelial function may contribute to explain the association. We conducted a meta-analysis to assess the effect of omega-3 FAs supplementation on endothelial function, as measured by flow-mediated dilation (FMD) and endothelium independent vasodilation (EIV). METHODS: Randomized placebo-controlled trials (RCTs) were identified from the databases of PubMed, EMBASE and Cochrane library by two investigators and the pooled effects were measured by weighted mean difference (WMD), together with 95% confidence intervals (CIs). Subgroup and meta regression analyses were used to explore the source of between-study heterogeneity. RESULTS: Totally 16 eligible studies involving 901 participants were finally included in meta-analysis. Compared with placebo, omega-3 FAs supplementation significantly increased FMD by 2.30% (95% CI: 0.89-3.72%, P = 0.001), at a dose ranging from 0.45 to 4.5 g/d over a median of 56 days. Subgroup analyses suggested that the effect of omega-3 FAs on FMD might be modified by the health status of the participants or the dose of supplementation. Sensitivity analyses indicated that the protective effect of omega-3 on endothelial function was robust. No significant change in EIV was observed after omega-3 FAs supplementation (WMD: 0.57%; 95% CI: -0.88 to 2.01%; P = 0.442). CONCLUSION: Supplementation of omega-3 fatty acids significantly improves the endothelial function without affecting endothelium-independent dilation. PMID- 22317967 TI - Choosing the optimal wall shear parameter for the prediction of plaque location-A patient-specific computational study in human left coronary arteries. AB - OBJECTIVE: While the correlation of atherosclerotic plaque locations with local wall shear stress magnitude has been evaluated previously by other investigators in both right (RCA) and left coronary arteries (LCA), the relative performance of average wall shear stress (AWSS), average wall shear stress gradient (AWSSG), oscillatory shear index (OSI) and relative residence time (RRT) as indicators of potential atherosclerotic plaque locations has not been studied for the LCA. Here we determine the performance of said wall shear parameters in the LCA for the prediction of plaque development locations and compare these results to those previously found in the RCA. METHODS: We obtained 30 patient-specific geometries (mean age 67.1 (+/- 9.2) years, all with stable angina) of the LCA using dual source computed tomography and virtually removed any plaque present. We then performed computational fluid dynamics simulations to calculate the wall shear parameters. RESULTS: For the 96 total plaques, AWSS had a higher sensitivity for the prediction of plaque locations (86 +/- 25%) than AWSSG (65 +/- 37%, p<0.05), OSI (67 +/- 32%, p<0.01) or RRT (48 +/- 38%, p<0.001). RRT had a higher PPV (49 +/- 36%) than AWSS (31 +/- 20%, p<0.05) or AWSSG (16 +/- 12%, p<0.001). Segment 5 of the LCA presented with overall low values for sensitivity and PPV. Parameter performance in the remainder of the LCA was comparable to that in the RCA. CONCLUSIONS: AWSS features remarkably high sensitivity, but does not reach the PPV of RRT. This may indicate that while low wall shear stress is necessary for plaque formation, its presence alone is not sufficient to predict future plaque locations. Time dependent factors have to be taken into account as well. PMID- 22317969 TI - Perioperative immunonutrition for gastrointestinal cancer: a systematic review of randomized controlled trials. AB - BACKGROUND: To improve the clinical outcome, immunonutrition (IN) was usually used in the patients undergoing elective gastrointestinal caner surgery. However, its effectiveness remains uncertain. METHODS: Randomized controlled trials (RCTs) published between 1995 and 2011 were identified and extracted by two reviewers independently from electronic databases, including PubMed, EMBASE, and Cochrane Library. The quality of included trials was assessed according to the handbook for Cochrane reviewer (V5.0.1). Statistical analysis was carried out with RevMan software. RESULTS: Nineteen RCTs involving a total of 2331 patients were included in our meta-analysis. The results showed perioperative IN significantly reduced length of hospital stay (WMD, -2.62; 95% CI, -3.26 to -1.97; P < 0.01) and morbidity of postoperative infectious complication (RR, 0.44; 95% CI, 0.32 to 0.60; P < 0.01) compared with standard diet. Moreover, perioperative IN also significantly decreased morbidity of postoperative non-infectious complication in comparison with standard diet (RR, 0.72; 95% CI, 0.54 to 0.97; P = 0.03). CONCLUSION: Perioperative IN is effective and safe to reduce postoperative infection, non-infection complication and length of hospital stay. PMID- 22317970 TI - Multiple meiotic errors caused by predivision of chromatids in women of advanced maternal age undergoing in vitro fertilisation. AB - Chromosome aneuploidy is a major cause of pregnancy loss, abnormal pregnancy and live births following both natural conception and in vitro fertilisation (IVF) and increases exponentially with maternal age in the decade preceding the menopause. Molecular genetic analysis following natural conception and spontaneous miscarriage demonstrates that trisomies arise mainly in female meiosis and particularly in the first meiotic division. Here, we studied copy number gains and losses for all chromosomes in the two by-products of female meiosis, the first and second polar bodies, and the corresponding zygotes in women of advanced maternal age undergoing IVF, using microarray comparative genomic hybridisation (array CGH). Analysis of the segregation patterns underlying the copy number changes reveals that premature predivision of chromatids rather than non-disjunction of whole chromosomes causes almost all errors in the first meiotic division and unlike natural conception, over half of aneuploidies result from errors in the second meiotic division. Furthermore, most abnormal zygotes had multiple aneuploidies. These differences in the aetiology of aneuploidy in IVF compared with natural conception may indicate a role for ovarian stimulation in perturbing meiosis in ageing oocytes. PMID- 22317971 TI - Permutation-based approaches do not adequately allow for linkage disequilibrium in gene-wide multi-locus association analysis. AB - Additional information about risk genes or risk pathways for diseases can be extracted from genome-wide association studies through analyses of groups of markers. The most commonly employed approaches involve combining individual marker data by adding the test statistics, or summing the logarithms of their P values, and then using permutation testing to derive empirical P-values that allow for the statistical dependence of single-marker tests arising from linkage disequilibrium (LD). In the present study, we use simulated data to show that these approaches fail to reflect the structure of the sampling error, and the effect of this is to give undue weight to correlated markers. We show that the results obtained are internally inconsistent in the presence of strong LD, and are externally inconsistent with the results derived from multi-locus analysis. We also show that the results obtained from regression and multivariate Hotelling T(2) (H-T2) testing, but not those obtained from permutations, are consistent with the theoretically expected distributions, and that the H-T2 test has greater power to detect gene-wide associations in real datasets. Finally, we show that while the results from permutation testing can be made to approximate those from regression and multivariate Hotelling T(2) testing through aggressive LD pruning of markers, this comes at the cost of loss of information. We conclude that when conducting multi-locus analyses of sets of single-nucleotide polymorphisms, regression or multivariate Hotelling T(2) testing, which give equivalent results, are preferable to the other more commonly applied approaches. PMID- 22317972 TI - Characterization of the intronic portion of cadherin superfamily members, common cancer orchestrators. AB - Cadherins are cell-cell adhesion proteins essential for the maintenance of tissue architecture and integrity, and their impairment is often associated with human cancer. Knowledge regarding regulatory mechanisms associated with cadherin misexpression in cancer is scarce. Specific features of the intronic-structure and intronic-based regulatory mechanisms in the cadherin superfamily are unidentified. This study aims at systematically characterizing the intronic portion of cadherin superfamily members and the identification of intronic regions constituting putative targets/triggers of regulation, using a bioinformatic approach and biological data mining. Our study demonstrates that the cadherin superfamily genes harbour specific characteristics in comparison to all non-cadherin genes, both from the genomic and transcriptional standpoints. Cadherin superfamily genes display higher average total intron number and significantly longer introns than other genes and across the entire vertebrate lineage. Moreover, in the human genome, we observed an uncommon high frequency of MIR (mammalian-wide interspersed repeats) and MaLR (mammalian-wide interspersed repeats, a subtype of LTR) regulatory-associated repetitive elements at 5' located introns, concomitantly with increased de novo intronic transcription. Using this approach, we identified cadherin intronic-specific sites that may constitute novel targets/triggers of cadherin superfamily expression regulation. These findings pinpoint the need to identify mechanisms affecting particularly MIR and MaLR elements located in introns 2 and 3 of human cadherin genes, possibly important in the expression modulation of this superfamily in homeostasis and cancer. PMID- 22317973 TI - C4ST-1/CHST11-controlled chondroitin sulfation interferes with oncogenic HRAS signaling in Costello syndrome. AB - Costello syndrome is a pediatric genetic disorder linked to oncogenic germline mutations in the HRAS gene. The disease is characterized by multiple developmental abnormalities, as well as predisposition to malignancies. Our recent observation that heart tissue from patients with Costello syndrome showed a loss of the glycosaminoglycan chondroitin-4-sulfate (C4S) inspired our present study aimed to explore a functional involvement of the chondroitin sulfate (CS) biosynthesis gene Carbohydrate sulfotransferase 11/Chondroitin-4-sulfotransferase 1 (CHST11/C4ST-1), as well as an impaired chondroitin sulfation balance, as a downstream mediator of oncogenic HRAS in Costello syndrome. Here we demonstrate a loss of C4S, as well as a reduction in C4ST-1 mRNA and protein expression, in primary fibroblasts from Costello syndrome patients. We go on to show that expression of oncogenic HRAS in normal fibroblasts can repress C4ST-1 expression, whereas interference with oncogenic HRAS signaling in Costello syndrome fibroblasts elevated C4ST-1 expression, thus identifying C4ST-1 as a negatively regulated target gene of HRAS signaling. Importantly, we show that forced expression of C4ST-1 in Costello fibroblasts could rescue the proliferation and elastogenesis defects associated with oncogenic HRAS signaling in these cells. Our results indicate reduced C4ST-1 expression and chondroitin sulfation imbalance mediating the effects of oncogenic HRAS signaling in the pathogenesis of Costello syndrome. Thus, our work identifies C4ST-1-dependent chondroitin sulfation as a downstream vulnerability in oncogenic RAS signaling, which might be pharmacologically exploited in future treatments of not only Costello syndrome and other RASopathies, but also human cancers associated with activating RAS mutations. PMID- 22317974 TI - The 12S rRNA A1555G mutation in the mitochondrial haplogroup D5a is responsible for maternally inherited hypertension and hearing loss in two Chinese pedigrees. AB - We reported here clinical, genetic evaluations and molecular analysis of mitochondrial DNA (mtDNA) in two Han Chinese families carrying the known mitochondrial 12S rRNA A1555G mutation. In contrast with the previous data that hearing loss as a sole phenotype was present in the maternal lineage of other families carrying the A1555G mutation, matrilineal relatives among these two Chinese families exhibited both hearing loss and hypertension. Of 21 matrilineal relatives, 9 subjects exhibited both hearing loss and hypertension, 2 individuals suffered from only hypertension and 1 member had only hearing loss. The average age at onset of hypertension in the affected matrilineal relatives of these families was 60 and 46 years, respectively, whereas those of hearing loss in these two families were 33 and 55 years, respectively. Molecular analysis of their mtDNA identified distinct sets of variants belonging to the Eastern Asian haplogroup D5a. In contrast, the A1555G mutation occurred among other mtDNA haplogroups D, B, R, F, G, Y, M and N, respectively. Our data further support that the A1555G mutation is necessary but by itself insufficient to produce the clinical phenotype. The other modifiers are responsible for the phenotypic variability of matrilineal relatives within and among these families carrying the A1555G mutation. Our investigation provides the first evidence that the 12S rRNA A1555G mutation leads to both of hearing loss and hypertension. Thus, our findings may provide the new insights into the understanding of pathophysiology and valuable information for management and treatment of maternally inherited hearing loss and hypertension. PMID- 22317975 TI - An exploration of genetic health professionals' experience with direct-to consumer genetic testing in their clinical practice. AB - Direct-to-consumer genetic testing (DTC-GT) allows individuals to obtain genetic tests directly from companies without necessarily involving health professionals. This study explores genetic health professionals' opinions of health-related DTC GT and the reported frequency of individuals presenting to clinical genetics services after undertaking testing. Genetic counsellors and clinical geneticists, members of the Human Genetics Society of Australasia, completed an online survey in mid 2011. The 130 genetic counsellors (estimated response fraction=43%) and 38 clinical geneticists (estimated response fraction=46%) had mixed opinions regarding DTC-GT, with only 7% confident in accurately interpreting and explaining DTC-GT results. Nineteen respondents (11%) reported one or more client(s) referred to them after undertaking DTC-GT. Descriptions of 25 clients were extracted from responses, and respondents reported that all clients were concerned for the health of either themselves or family members. Most clients presented to genetic clinics specifically as a result of their DTC-GT (96%) and were self or GP referred (92%). Respondents perceived that their clients typically undertook DTC-GT because they wanted to identify monogenic conditions, including carrier testing and/or know their susceptibility or predisposition for complex conditions (88%). The majority of clients needed help interpreting DTC-GT results (80%), however in general were not questioning the validity of their DTC GT results (92%) nor seeking further genetic testing (84%). Currently, DTC-GT is not a major reason for referral to clinical genetics services in Australia and New Zealand and the majority of genetic health professionals lack confidence in being able to accurately interpret and explain DTC-GT results. PMID- 22317976 TI - Gross deletions in TCOF1 are a cause of Treacher-Collins-Franceschetti syndrome. AB - Treacher-Collins-Franceschetti syndrome (TCS) is an autosomal dominant craniofacial disorder characterised by midface hypoplasia, micrognathia, downslanting palpebral fissures, eyelid colobomata, and ear deformities that often lead to conductive deafness. A total of 182 patients with signs consistent with a diagnosis of TCS were screened by DNA sequence and dosage analysis of the TCOF1 gene. In all, 92 cases were found to have a pathogenic mutation by sequencing and 5 to have a partial gene deletion. A further case had a novel in frame deletion in the alternatively spliced exon 6A of uncertain pathogenicity. The majority of the pathogenic sequence changes were found to predict premature protein termination, however, four novel missense changes in the LIS1 homology motif at the 5' end of the gene were identified. The partial gene deletions of different sizes represent ~5.2% of all the pathogenic TCOF1 mutations identified, indicating that gene rearrangements account for a significant proportion of TCS cases. This is the first report of gene rearrangements resulting in TCS. These findings expand the TCOF1 mutation spectrum indicating that dosage analysis should be performed together with sequence analysis, a strategy that is predicted to have a sensitivity of 71% for patients in whom TCS is strongly suspected. PMID- 22317978 TI - Immunoproteomics analysis of whole cell bacterial proteins of Riemerella anatipestifer. AB - Riemerella antipestifer is one of the most important duck pathogens. It has worldwide distribution, and the lack of the information on bacteria-host interactions and an effective vaccine are limitations on the control of this infection. In this study, an immunoproteomic assay was used to identify immunogenic proteins among the whole cell bacterial proteins of R. anatipestifer virulent strain Th4. Duck antiserum against R. anatipestifer Th4 recognized 64 protein spots which were transferred from two-dimensional electrophoresis (2-DE) gel of the whole cell bacterial proteins onto polyvinylidene fluoride (PVDF) membrane. Immunogenic proteins on a duplicate gel were excised and identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) and peptide mass fingerprinting (PMF), a total of 34 immunogenic proteins were found. With the exception of OmpA and GroEL, the other 32 proteins were newly recognized immunogenic antigens of R. anatipestifer. In addition, TonB dependent outer membrane receptor was found to be a cross immunogenic antigen among serotypes 1, 2 and 10 of R. anatipestifer. Bioinformatics analysis showed that most of the immunogenic proteins were located in the outer membrane and cytoplasm, and were involved in cellular processes and metabolism. The newly identified immunogenic proteins of R. anatipestifer may help us to uncover the pathogenesis of the bacteria, develop novel vaccine candidates and serological diagnosis marker. PMID- 22317979 TI - Identification and molecular characterization of a novel flavivirus isolated from Pekin ducklings in China. AB - A flavivirus-associated disease of egg-laying ducks was observed in eastern China in 2010, and a novel mosquito-borne flavivirus, Tembusu virus (TMUV), was isolated (Cao et al., 2011). Following up on the earlier study, a virus similar to TMUV was isolated recently from ducklings and characterized. We report that (1) the recently isolated virus, TMUV ZJ-6, replicated in vertebrate cells (DF-1, BHK-21) as well as in mosquito cells (C6/36) and caused cytopathic effect (CPE) in the cell lines tested; (2) extracellular viral particles examined by electron microscopy were approximately 45 nm in diameter and enveloped; (3) the full length genome of the virus was determined, showing that the TMUV ZJ-6 is more closely related to the Ntaya group of viruses than other members of the Flaviviridae based on the data of phylogenetic analyses. Most importantly, the disease of ducklings was reproducible after administration of plaque-purified virus by intracerebral (i.c.), subcutaneous (s.c.) or intranasal (i.n.) inoculation. This is the first report that TMUV infects not only egg-laying ducks but also 3-21 days-old ducklings. The findings extend our understanding of how the virus spreads and causes disease. PMID- 22317977 TI - Proximal microdeletions and microduplications of 1q21.1 contribute to variable abnormal phenotypes. AB - Chromosomal band 1q21.1 can be divided into two distinct regions, proximal and distal, based on segmental duplications that mediate recurrent rearrangements. Microdeletions and microduplications of the distal region within 1q21.1, which are susceptibility factors for a variety of neurodevelopmental phenotypes, have been more extensively studied than proximal microdeletions and microduplications. Proximal microdeletions are known as a susceptibility factor for thrombocytopenia absent radius (TAR) syndrome, but it is unclear if these proximal microdeletions have other phenotypic consequences. Therefore, to elucidate the clinical significance of rearrangements of the proximal 1q21.1 region, we evaluated the phenotypes in patients identified with 1q21.1 rearrangements after referral for clinical microarray testing. We report clinical information for 55 probands with copy number variations (CNVs) involving proximal 1q21.1: 22 microdeletions and 20 reciprocal microduplications limited to proximal 1q21.1 and 13 microdeletions that include both the proximal and distal regions. Six individuals with proximal microdeletions have TAR syndrome. Three individuals with proximal microdeletions and two individuals with larger microdeletions of proximal and distal 1q21.1 have a 'partial' TAR phenotype. Furthermore, one subject with TAR syndrome has a smaller, atypical deletion, narrowing the critical deletion region for the syndrome. Otherwise, phenotypic features varied among individuals with these microdeletions and microduplications. The recurrent, proximal 1q21.1 microduplications are enriched in our population undergoing genetic testing compared with control populations. Therefore, CNVs in proximal 1q21.1 can be a contributing factor for the development of abnormal phenotypes in some carriers. PMID- 22317980 TI - A novel three-way variant t(4;17;5)(p16;q23;q31) in a case of secondary plasma cell leukemia. PMID- 22317981 TI - Sonographic measurement of renal size in normal Indian children. AB - OBJECTIVES: To determine the renal size in normal Indian children by sonography. SETTINGS: Pediatric teaching hospital, Mumbai, India. DURATION: 1.5 years. DESIGN: Cross-sectional observational study. PARTICIPANTS: 1000 normal Indian children aged 1 month to 12 years. METHODS: Sonographic assessment of renal size (length, width and thickness) was performed using Philips real time mechanical sector scanner of 3.5-5 MHz frequency with electronic caliper. The mean renal dimensions and volume were calculated for each age group with +/- 2SD. The renal length and calculated renal volume were correlated with somatic parameters like age, weight, height and body surface area. Regression equations were derived for each pair of dependent and independent variables. RESULTS: No statistical difference was found in renal size between sexes and between right and left kidney. A strong correlation was seen between renal size with various somatic parameters, the best correlation was between renal size length and body height (coefficient of correlation=0.9). CONCLUSION: This study provides values of renal length (mean +/- 2SD) in normal Indian children. Renal length can be easily calculated by derived linear regression equation. PMID- 22317982 TI - Patent ductus arteriosus in infants <29 weeks gestation--outcomes and factors affecting closure. AB - OBJECTIVE: To determine Patent ductus arteriosus (PDA) closure rates for extremely preterm infants in a tertiary care centre, factors affecting response to indomethacin and outcomes of these infants relative to their PDA status. SETTING: Neonatal intensive care unit in tertiary-care children's hospital. DESIGN: Retrospective medical record review. METHODS: A retrospective chart review of all infants <29 weeks gestation between 1st Jan 2003 and 30th June 2006 was carried out. Multiple courses of standard intravenous indomethacin (dose: 0.2 mg/kg 12 hourly; 3 doses) followed by a tail course (0.1 mg/kg/day; 3 doses) were used to treat PDA depending on clinical and hemodynamic status. Data on demographic characteristics, PDA status, use of indomethacin, and outcome factors such as chronic lung disease and mortality were collected. RESULTS: A total of 166 infants were identified in the study period, of which 15 were excluded. The median gestation was 27 weeks [IQR (25, 28)] and the mean (SD) birthweight was 950 (244) grams. The remaining infants (n=151) were divided into three groups. Group1 (n=47): no or non-significant PDA, Group 2 (n=91): significant PDA closed after indomethacin treatment (= 1 course) and Group 3 (n=13): significant PDA not responding to indomethacin. The closure rate of PDA with indomethacin treatment (group 2) was 87%. A low gestational age < 26 weeks (OR 5.6, 95% CI 1.6-19.9) and female sex (OR 5.8, 95% CI 1.5-22.8) was associated with poor response to indomethacin in our study population. CONCLUSIONS: Multiple indomethacin courses using the standard dosing approach result in high PDA closure rates for infants < 29 weeks gestation. PMID- 22317983 TI - Blood levels of pyrazinamide in children at doses administered under the Revised National Tuberculosis Control Program. AB - OBJECTIVES: To evaluate the blood levels, pharma-cokinetics and pharmacodynamic indices of pyrazinamide (PZA) in children suffering from tuberculosis, at doses administered under the weight band system of Revised National Tuberculosis Control Program of India (RNTCP) of India. DESIGN: Prospective, open-label, non randomized single-dose study. SETTING: 20 children in the age group 5-12 years attending out-patient tuberculosis clinic of a tertiary hospital. OUTCOME MEASURES: Blood levels of pyrazinamide after single dose administration, as per the weight band system of RNTCP. RESULTS: Group I (n=7) included children who received pyrazinamide within the recommended 30-35 mg/kg dose (mean 31.9 +/- 0.8 mg/kg) and Group II (n=13) included those who received a dose lower than 30 -35 mg/kg (mean 28.1 +/- 0.3 mg/kg). The Cmax (95% CI of difference 2.2, 13.2; P=0.008) and AUC (95% CI of difference 28.6, 208.1; P=0.01) were significantly lower in Group II. The duration of time for which the concentration was maintained above 25 ug ml-1 was 4-8 h in Group I and 3-5.5 h in Group II (95% CI of difference 0.1, 2.0; P=0.03). The half life, elimination rate constant, clearance and volume of distribution were comparable in the two groups. The ratios of Cmax and AUC to MIC (25 ug ml-1) in children were lower than that recommended for PZA in adults. CONCLUSIONS: Lower blood concentrations are being attained in children receiving PZA doses under the existing weight band system of RNTCP of India. The weight bands may need to be revised and dose recommendations be based on pharmacokinetic and efficacy data in children. PMID- 22317984 TI - Incidence of acute kidney injury in hospitalized children. AB - OBJECTIVE: To determine the incidence and outcome of acute kidney injury (AKI) in hospitalized patients. DESIGN: Prospective, observational. SETTING: Tertiary care center in North India. PARTICIPANTS/PATIENTS: Inpatients, 1 month to 18 yrs. INTERVENTION: None. MAIN OUTCOME MEASURES: Incidence of AKI based on the serum creatinine criteria proposed by the AKI Network. RESULTS: During February to September 2008, thirty nine of 108 (36.1%) critically ill patients and 34 of 378 (9.0%) patients who were not critically ill developed AKI (P<0.001); the respective incidence densities were 45.1 and 11.7 cases/1000 patient days, respectively. The maximal stage of AKI was stage 1 in 48 (65.8%) patients, stage 2 in 13 (17.8%) and stage 3 in 12 (16.4%) patients; 11 (15.1%) required dialysis. Patients with AKI had a significantly longer duration of hospital stay (9 days vs 7 days, P<0.02) and higher mortality (37% vs 8.7%; hazard ratio, HR 2.73; 95% CI 1.64, 4.54). Independent risk factors for AKI were young age (HR 0.89; 95% CI 0.83, 0.95), shock (HR 2.65; 95% CI 1.32, 5.31), sepsis (HR 3.64; 95% CI 2.20, 6.01), and need for mechanical ventilation (2.18; 95% CI 1.12, 4.26). Compared to patients without AKI, the mortality was higher for AKI stage 2 (HR 5.18; 95% CI 2.59, 10.38) and stage 3 (HR 4.34; 95% CI 2.06, 9.16). Shock was an independent risk factor for mortality (HR 10.7; 95% CI 4.96, 22.98). CONCLUSIONS: AKI is common in critically ill children, especially younger patients with septicemia and shock, and results in increased hospital stay and high mortality. PMID- 22317985 TI - Waist to height ratio and elevated blood pressure among children in Taiwan. AB - OBJECTIVES: To study the association of waist to height ratio (WHtR) and elevated blood pressure (BP) in children. STUDY DESIGN: Cross-sectional study. SETTING: Six elementary schools in Taipei, Taiwan. PARTICIPANTS: All children aged 7 years at first grade. METHODS: We measured anthropometrics and BP during the regular health examinations among children. MAIN OUTCOME MEASURES: Elevated BP in children was defined as an average systolic BP or diastolic BP greater than or equal to the gender, age, and height-percentile-specific 95th percentile BP value. RESULTS: Among 2,334 eligible school children, the averages of systolic BP and diastolic BP increased with quartiles of WHtR. The prevalence of elevated BP in children among the first quartile of WHtR was 8.8% and increased to 31.2% among the fourth quartile of WHtR (P < 0.0001). Children among the first quartile of WHtR being reference, the adjusted odds ratio of elevated BP for children among the fourth quartile of WHtR was 3.10. The odds ratio of elevated BP with per 0.01 increase of WHtR was 1.11. CONCLUSIONS: WHtR, simple to measure, is an important factor associated with elevated BP in children. PMID- 22317986 TI - Validity of two point of care glucometers in the diagnosis of neonatal hypoglycemia. AB - OBJECTIVE: To estimate validity of two point of care glucometers for the diagnosis of neonatal hypoglycemia and to determine the glucometers cut off values for which standard laboratory confirmatory test are no longer needed. DESIGN: Prospective study. SETTINGS: A tertiary care, university hospital in Bangkok, Thailand. PARTICIPANTS: The study included 180 blood specimens from 166 high risk neonates aged between 1-24 hours. RESULTS: On average, most of the blood glucose read-outs from the Nova StatStrip and SureStep were higher than laboratory plasma glucose throughout the glucose range with mean differences (SD) of 11.2 (8.4) mg/dL and 13.7 (6.8) mg/dL, respectively. Sensitivity of Nova StatStrip and SureStep were 62% and 53.3%, respectively. Specificity and positive predictive value of both glucometers were 100%. Negative predictive values of both glucometers were approximately 85%. The cut-off levels with 100% negative predictive values were 63 mg/dL and 62 mg/dL for Nova StatStrip and SureStep, respectively. CONCLUSIONS: None of the glucometers in this study has sufficient validity to replace laboratory testing in diagnosing hypoglycemia. Confirmatory plasma glucose for diagnosis of hypoglycemia is needed when POC readings are between 39 and 63 mg/dL for Nova StatStrip and between 39 and 62 mg/dL for SureStep. PMID- 22317987 TI - Maintaining reduced noise levels in a resource-constrained neonatal intensive care unit by operant conditioning. AB - OBJECTIVE: To evaluate the efficacy of operant conditioning in sustaining reduced noise levels in the neonatal intensive care unit (NICU). DESIGN: Quasi experimental study on quality of care. SETTING: Level III NICU of a teaching hospital in south India. PARTICIPANTS: 26 staff employed in the NICU. (7 Doctors, 13 Nursing staff and 6 Nursing assistants). INTERVENTION: Operant conditioning of staff activity for 6 months. This method involves positive and negative reinforcement to condition the staff to modify noise generating activities. MAIN OUTCOME MEASURES: Comparing noise levels in decibel: A weighted [dB (A)] before conditioning with levels at 18 and 24 months after conditioning. Decibel: A weighted accounts for noise that is audible to human ears. RESULTS: Operant conditioning for 6 months sustains the reduced noise levels to within 62 dB in ventilator room 95% CI: 60.4 - 62.2 and isolation room (95% CI: 55.8 - 61.5). In the preterm room, noise can be maintained within 52 dB (95% CI: 50.8 - 52.6). This effect is statistically significant in all the rooms at 18 months (P = 0.001). At 24 months post conditioning there is a significant rebound of noise levels by 8.6, 6.7 and 9.9 dB in the ventilator, isolation and preterm room, respectively (P =0.001). CONCLUSION: Operant conditioning for 6 months was effective in sustaining reduced noise levels. At 18 months post conditioning, the noise levels were maintained within 62 dB (A), 60 dB (A) and 52 dB (A) in the ventilator, isolation and pre-term room, respectively. Conditioning needs to be repeated at 12 months in the ventilator room and at 18 months in the other rooms. PMID- 22317988 TI - Form, function and evolution of the mouthparts of blood-feeding Arthropoda. AB - This review compares the mouthparts and their modes of operation in blood-feeding Arthropoda which have medical relevance to humans. All possess piercing blood sucking proboscides which exhibit thin stylet-shaped structures to puncture the host's skin. The tips of the piercing structures are serrated to provide anchorage. Usually, the piercing organs are enveloped by a soft sheath-like part which is not inserted. The piercing process includes either back and forth movements of the piercing structures, or sideways cutting motions, or the apex of the proboscis bears teeth-like structures which execute drilling movements. Most piercing-proboscides have a food-canal which is separate from a salivary canal. The food-canal is functionally connected to a suction pump in the head that transports blood into the alimentary tract. The salivary canal conducts saliva to the tip of the proboscis, from where it is discharged into the host. Piercing blood-sucking proboscides evolved either from (1) generalized biting-chewing mouthparts, (2) from piercing mouthparts of predators, or plant sap or seed feeders, (3) from lapping or sponging mouthparts. Representatives of one taxon of Acari liquefy skin tissue by enzymatic action. During feeding, many blood-feeding arthropods inadvertently transmit pathogens, which mostly are transported through the discharged saliva into the host. PMID- 22317989 TI - [Maxillary sinusitis of odontogenic origin: surgical treatment]. AB - PURPOSE: The frequency of maxillary sinusitis of dental origin (MSDO) is under estimated. The medical and surgical treatment has improved thanks to endoscopic guidance. We report our experience and strategy in the treatment of MSDO. PATIENTS AND METHODS: Twenty-two patients presenting with MSDO were treated between 1998 and 2008. The results were evaluated on clinical, functional, sinusal, and odontologic signs. RESULTS: MSDO accounted for 16% of surgically managed sinusitis. CT was performed in 95% of cases. The etiologies were apical leakage in seven patients, migration of a tooth or root during extraction, or presence of ectopic tooth in the sinus in nine patients, a cyst in three patients, and oroantral communication in three patients. Surgery was performed after antibiotic and NSAID treatment. The first surgical step was the treatment of the odontogenic source. The second step was sinus drainage by endoscopic treatment in 64%, Caldwell-Luc in 23%, and drainage by oroantral communication enlarged then closed in the same operative time in 13%. The follow up ranged from 3 months to 10 years. Early postoperative superinfection was observed in two patients. Two patients presented with recurrent sinusitis. The postoperative sequels were hyposmia in three patients, dental pulpotomy, and trigeminal neuralgia in five patients treated by Caldwell-Luc surgery. DISCUSSION: Nasal endoscopy has improved the surgical management of MSDO. It makes curettage and exclusion of sinus cavities obsolete. It is reliable and has a low rate of complications. The best treatment remains prevention. PMID- 22317990 TI - Home blood pressure monitoring may make office measurements obsolete. PMID- 22317991 TI - Can ambulatory blood pressure serve as a biomarker for presence of chronic kidney disease? PMID- 22317992 TI - The mutual exacerbation of decreased kidney function and hypertension. PMID- 22317993 TI - Selective renin inhibition in obese hypertensive patients: perspectives from tissue penetration. PMID- 22317994 TI - What are the real determinants of the ambulatory arterial stiffness index? PMID- 22317995 TI - Microcirculation and left-ventricular hypertrophy. PMID- 22317996 TI - Full health coverage improves compliance of 50%. PMID- 22317997 TI - A simple test to appreciate compliance with antihypertensive drug therapy. PMID- 22317999 TI - Nitric oxide and hypertension. PMID- 22318001 TI - Angiotensin II type 2 receptors mediating both vasoconstriction and vasodilation in humans: support from data in a human model of endogenous angiotensin II type 1 receptor antagonism. PMID- 22318002 TI - Health-related quality of life and awareness of hypertension. PMID- 22318003 TI - New insights on the relationship between pseudotumor cerebri and secondary hyperaldosteronism in children. PMID- 22318004 TI - Synthesis of molecularly imprinted polymer using attapulgite as matrix by ultrasonic irradiation for simultaneous on-line solid phase extraction and high performance liquid chromatography determination of four estrogens. AB - A molecularly imprinted polymer was synthesized by ultrasonic irradiation, with attapulgite as matrix using beta-naphthol as the template molecule, acryloyl-beta cyclodextrin as the functional monomer, and N,N-methylenebiacrylamide as the cross-linking agent, respectively. The imprinted polymer was characterized by infrared spectroscopy and transmission electron microscopy. Compared to polymers prepared by traditional heat sources, the molecularly imprinted polymer synthesized by ultrasonic irradiation had better selectivity and faster adsorption kinetics to estriol, estradiol, estrone and diethylstilbestrol. Using the imprinted polymer as the packing material for on-line solid-phase extraction, the above four estrogens in milk samples were concentrated and analyzed. The limits of detection for these estrogens were in the range of 1-8 ng g(-1) and reproducibility were less than 5.1% as RSDs (n=6) with milk samples spiked at 100 and 1000 ng g(-1) of each analyte. PMID- 22318005 TI - Development of a hydrophilic interaction liquid chromatography-mass spectrometry method for detection and quantification of urea thermal decomposition by-products in emission from diesel engine employing selective catalytic reduction technology. AB - The use of urea based selective catalytic reduction (SCR) technology for the reduction of NOx from the exhaust of diesel-powered vehicles has the potential to emit at least six thermal decomposition by-products, ammonia, and unreacted urea from the tailpipe. These compounds may include: biuret, dicyandiamine, cyanuric acid, ammelide, ammeline and melamine. In the present study, a simple, sensitive and reliable hydrophilic interaction liquid chromatography (HILIC)-electrospray ionization (ESI)/mass spectrometry (MS) method without complex sample pre treatment was developed for identification and determination of urea decomposition by-products in diesel exhaust. Gradient separation was performed on a SeQuant ZIC-HILIC column with a highly polar zwitterionic stationary phase, and using a mobile phase consisting of acetonitrile (eluent A) and 15 mM ammonium formate (pH 6; eluent B). Detection and quantification were performed using a quadrupole ESI/MS operated simultaneously in negative and positive mode. With 10 MUL injection volume, LODs for all target analytes were in the range of 0.2-3 MUg/L. The method showed a good inter-day precision of retention time (RSD<0.5%) and peak area (RSD<3%). Satisfactory extraction recoveries from spiked blanks ranged between 96 and 98%. Analyses of samples collected during transient chassis dynamometer tests of a bus engine equipped with a diesel particulate filter (DPF) and urea based SCR technology showed the presence of five target analytes with cyanuric acid and ammelide the most abundant compounds in the exhaust. PMID- 22318006 TI - Evaluation of the influence of mobile data terminal location on physical exposures during simulated police patrol activities. AB - Prolonged occupational police driving combined with use of an in-vehicle computer elicits awkward, sustained postures in a scenario that lacks the adjustability to accommodate many mobile officer anthropometries and job-specific components. Twenty participants performed simulated police patrol sessions at five mobile data terminal (MDT) locations and using two seats: standard police vehicle seat and modified seat designed for police use. An MDT location self-selected prior to the session reduced perceived discomfort by up to 50% in the low back (p < .0001) and 68% in the right shoulder (p < .0001) compared to other tested locations, including the most common currently used location recorded from a representative police force. Muscle activity was lowest at the self-selected and current MDT locations for all muscles, significantly so for posterior deltoid (p < .0001) and supraspinatus (p < .0001). The modified seat reduced low back discomfort from the standard seat by 28% (p < .0001). Combining a self-selected MDT location and modified driver seat generated lower discomfort and physical loading than the currently used configuration. PMID- 22318007 TI - Vasopressor use in adult patients. AB - Vasopressors are a heterogeneous potent class of medications designed to increase blood pressure in emergent hypotensive situations. The goal of therapy is to increase blood pressure and maintain adequate perfusion, allowing nutrient and oxygen delivery to vital organs. Norepinephrine, phenylephrine, dopamine, epinephrine, and vasopressin are five vasopressors available in the United States. All vasopressors, with the exception of vasopressin, are titratable and dosed on a continuum according to clinical effect. With their different clinical features, adverse effects, and range of potency, the clinical situation usually guides therapy. Outcome data comparing different vasopressors have not demonstrated a clear mortality benefit of any one vasopressor over another, and physician preference also guides therapy. Norepinephrine, nonetheless, remains one of the preferred choices for a variety of hypotensive states, including cardiogenic and septic shock. PMID- 22318008 TI - Effects of ethinylestradiol and of an environmentally relevant mixture of xenoestrogens on steroidogenic gene expression and specific transcription factors in zebrafish. AB - In natural environments fish are exposed to endocrine disrupting compounds (EDCs) present at low concentrations and with different modes of actions. Here, adult zebrafish of both sexes were exposed for 21 days to an estrogenic mixture (Mix) of eleven EDCs previously quantified in Douro River estuary (Portugal) and to 100 ng/L 17alpha-ethinylestradiol (EE2) as positive control. Vitellogenin mRNA and HSI in males confirmed both exposure regimes as physiologically active. Potential candidates for estrogenic disturbance of steroidogenesis were identified (StAR, 17beta-HSD1, cyp19a1), but Mix only affected cyp19a1 in females. Significant differences in the response of FSHbeta, cypa19a2, 20beta-HSD were observed between EE2 and Mix. Mtf-1 and tfap2c transcription factor binding sites were discovered in the putative promoter regions and corresponding transcription factors were found to be differentially expressed in response to Mix and EE2. The results suggest that "non-classical effects" of estrogenic EDC in fish are mediated via transcription factors. PMID- 22318009 TI - Comparison of the various lipid ratios and indices for risk assessment in patients of myocardial infarction. AB - OBJECTIVES: Coronary artery disease (CAD) has emerged as the major cause of morbidity and mortality among Asian Indians in the recent past. The following study was undertaken to assess the predictive value of novel biomarkers of dyslipidemia for risk assessment for CAD in the Indian population. DESIGN AND METHODS: The study group comprised of 100 clinically assessed patients of myocardial infarction and 100 age and sex matched healthy controls. Apolipoprotein-A (Apo-AI) and Apolipoprotein-B (Apo-B) were estimated and small dense LDL was derived mathematically. RESULTS: The cases showed significantly high levels of total serum cholesterol, triglycerides, LDL cholesterol, Apo-B, sdLDL, and non-HDL cholesterol. On carrying out multivariate regression analysis, Lp(a)/HDL ratio emerged as the best determinant of CAD risk CONCLUSION: The above data clearly underlines the role of these novel biomarkers in the risk assessment for CAD in the Indian context. PMID- 22318010 TI - Why genies don't go back into bottles. PMID- 22318011 TI - Big pharma upheavals cast shadow across biotech sector. PMID- 22318013 TI - Sangamo's lead zinc-finger therapy flops in diabetic neuropathy. PMID- 22318016 TI - Enbrel patent surfaces. PMID- 22318018 TI - Toll-like receptor blocker slows beta cell death in type 1 diabetes. PMID- 22318020 TI - UK government unveils innovation booster. PMID- 22318022 TI - Life Technologies promises $1,000 genome. PMID- 22318024 TI - Fresh from the biotech pipeline--2011 [corrected]. PMID- 22318025 TI - Planning for the exit. PMID- 22318026 TI - PRIDE Inspector: a tool to visualize and validate MS proteomics data. PMID- 22318027 TI - OpenVigil--free eyeballs on AERS pharmacovigilance data. PMID- 22318028 TI - The blinded buyer. PMID- 22318029 TI - Personal medicine--the new banking crisis. PMID- 22318030 TI - Funding and performance at the US Patent and Trademark Office. PMID- 22318032 TI - Smooth muscle diversity from human pluripotent cells. PMID- 22318033 TI - Complex binding sites made to order. PMID- 22318034 TI - Gene-based passive antibody protection from HIV. PMID- 22318050 TI - The appendiceal stump closure during laparoscopy: historical, surgical, and future perspectives. AB - During a laparoscopic appendectomy, the closure of the appendiceal stump is an important step because of postoperative complications from its inappropriate management. The development of life-threatening events such as stercoral fistulas, postoperative peritonitis, and sepsis is feared and unwanted. The tactical modification of the appendiceal stump closure with a single endoligature, replacing the invaginating suture, adjusted very well to laparoscopic appendectomy, and nowadays is the procedure of choice, whenever possible. Among the alternatives that do not make use of an invaginating suture, studies advocate the use of an endostapler, endoligature (endo-loop), metal clips, bipolar endocoagulation, and polymeric clips. All alternatives have advantages and disadvantages against the different clinical stages of acute appendicitis, and it should be noted that the different forms of appendiceal stump closure have never been assessed in prospective randomized studies. Knowledge about and appropriate use of all of them are important for a safe and more cost-effective procedure. PMID- 22318051 TI - Lymph node harvested in laparoscopic versus open colorectal cancer approaches: a meta-analysis. AB - Increasing researches have reported the safety and efficacy of laparoscopic versus open approach for colorectal cancer resection; however, the number of lymph nodes harvested in the 2 approaches is still unclear. This meta-analysis is to compare the number of lymph node harvested in these 2 methods. We searched the PUBMED, the EMBASE, and the Cochrane Library up to July 1, 2011 for relevant studies. Twenty-four randomized controlled trials, comprising 6264 participants, met our criterion. We found no difference in the number of lymph nodes harvested in these 2 approaches (weighted mean difference=-0.25; 95% confidence interval, 0.57 to 0.08; P=0.542), as well as in subgroups of colon cancer and of rectal cancer. Our meta-analysis suggests that laparoscopic surgery could achieve the same effectiveness with open surgery in relation to lymph node harvested. Surgeons should pay appropriate attention on the excision of lymph nodes, which are associated with long-term benefits of patients. PMID- 22318052 TI - Single-incision laparoscopic cholecystectomy versus laparoscopic cholecystectomy: a prospective randomized study. AB - This prospective randomized study compared single-incision laparoscopic cholecystectomy (SILC) and laparoscopic cholecystectomy (LC) with respect to estimated blood loss, operative time, postoperative pain levels, and complications. Thirty-four study patients were divided into 2 groups: 17 patients underwent SILC and 17 underwent LC. Operative time was longer for SILC than for LC, and the difference was statistically significant (P<0.001). There was no statistically significant difference in the relationship of body mass index with operative time between SILC and LC (P=0.613, P=0.983, respectively). The 2 groups had no statistically significant differences with respect to visual analog scale scores, estimated blood loss, shoulder pain, or complications (P>0.05). SILC can be the treatment of choice for gallbladder disease. Although the surgeon's first several attempts at SILC require a longer operative time compared with LC, there are no differences in hospital length of stay, blood loss, complication rates, or pain scores between SILC and LC. PMID- 22318053 TI - Single-incision laparoscopic cholecystectomy using glove port in comparison with standard laparoscopic cholecystectomy SILC using glove port. AB - PURPOSE: Surgery with minimal scar has become a widely used surgical method during the last decade. Single-incision laparoscopic cholecystectomy (SILC) promises better cosmetic results and probably less pain compared with conventional laparoscopy. METHODS: In a period of 5 months, data were collected and analyzed from patients, who underwent SILC using the Glove port. Another group of patients who underwent standard laparoscopic cholecystectomy during the same period has been taken as control group. Demographic data, operative time, successfulness of operation, length of hospital stay, and postoperative findings were collected. RESULTS: Twenty-five patients underwent SILC and 30 patients underwent the standard procedure. There were no conversions to open procedure in either group. No major complications occurred. Operative time in SILC cases was significantly more than the standard technique, whereas postoperative pain in the SILC group was considerably less. CONCLUSIONS: It seems that in selected patients (with a low risk of adhesions or technical difficulty), SILC can be an acceptable alternative to standard laparoscopic cholecystectomy with acceptable results. PMID- 22318054 TI - Systemic inflammatory response after single-incision laparoscopic surgery versus standard laparoscopic approach. AB - PURPOSE: The extent of surgical trauma is reflected by systemic inflammatory response (SIR). The aim of this study was to assess SIR after single-incision laparoscopic surgery (SILS) versus the standard laparoscopic approach. MATERIALS AND METHODS: Twenty pigs were assigned into 4 groups: SILS (group SILS), laparoscopy using 4 trocars (group LAPSC), pneumoperitoneum (group PNE), or a sham-operation (group Sham) group. Blood samples were taken at 0, 1, 3, 6, 24, and 48 hours and 1 week postoperation to measure tumor necrosis factor-alpha, interleukin (IL)-6, IL-18, and C-reactive protein serum levels. RESULTS: No significant changes were noted among groups for each time point studied regarding tumor necrosis factor-alpha, IL-6, and IL-18. C-reactive protein levels were significantly lower (P<0.05) in group PNE compared with the other groups at 24 hours, 48 hours, and 1 week. CONCLUSIONS: There is no difference in SIR after SILS versus the standard laparoscopic approach. PMID- 22318055 TI - Comparison of postoperative pain between single-incision laparoscopic cholecystectomy and conventional laparoscopic cholecystectomy: prospective case control study. AB - BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) is an emerging technique used in cholecystectomy. Nevertheless, studies on the difference in postoperative pain between SILC and conventional laparoscopic cholecystectomy are lacking in the literature. PATIENT AND METHODS: From August 2009 to July 2010, 20 consecutive patients who underwent SILC (SILC group) were compared with a prospective cohort of 20 patients who underwent conventional 4-port laparoscopic cholecystectomy (LC group) during the same period. Standard postoperative analgesic protocol was applied to all patients. Pain scores were registered before operation and one day after operation using visual analog scale. Satisfactory score was self-assessed by all patients one month after surgery using visual analog scale. RESULTS: There was no significant difference in the baseline characteristics, preoperative pain score, and intraoperative opioid usage between the 2 groups. The postoperative pain score was significantly lower in the SILC group (2.9+/-1.6 in SILC group vs. 4.8+/-1.5 in LC group, P<0.01). There was also a lower analgesic consumption and a higher satisfactory score in the SILC group although the results did not reach statistical significance. CONCLUSIONS: SILC resulted in significantly less postoperative pain than conventional laparoscopic cholecystectomy. It is a safe alternative to conventional laparoscopic cholecystectomy. PMID- 22318056 TI - Single-center comparative study of laparoscopic versus open colorectal surgery: a 2-year experience. AB - AIM: To examine the change in practice from open to laparoscopic practice in our local trust, a national training colorectal unit. METHODS: Retrospective comprehensive review of clinical case notes of all colorectal resections between October 2007 and October 2009. Patients were identified through clinical coding and data were analyzed using SPSS. RESULTS: Comparison of 113 open versus 103 laparoscopic colorectal surgeries for various indications and short-term outcomes was made. There was an expected overall increase in the laparoscopic colorectal resections. The mean age was 73 years for open and 68 years for laparoscopic surgeries. There was no significant difference between the 2 groups with respect to age, sex, and the American Society of Anaesthesiologists. Of the 103 patients who were initially treated with laparoscopy-assisted colectomy, 12 (11.7%) were shifted to open procedures. Perioperative recovery was faster in the laparoscopic surgery group than in the open-colectomy group, as reflected by a shorter hospital stay (median, 8 vs. 13 d). The overall complication rate was significantly less in the laparoscopy-assisted colectomy group than in the open colectomy group (33% vs. 46%, P=0.05). CONCLUSIONS: Our local hospital practices support the many benefits of laparoscopic colorectal surgery. Substantial improvements in rates of hospital stay and wound infection were noted, hence shifting our practice safely in a district general hospital. PMID- 22318057 TI - Adequacy of lymphadenectomy in laparoscopic colorectal cancer surgery: a single centre, retrospective study. AB - PURPOSE: This study aimed at evaluating the lymph node (LN) harvest after both open and laparoscopic colorectal cancer surgery. METHODS: In the period between 1996 and 2009, 404 patients with colorectal cancer underwent open resection, whereas 147 patients underwent laparoscopic surgery. RESULTS: The overall number of harvested LNs was significantly higher in the laparoscopic group than in the open one (16.5 vs. 14.3, P<0.001). A higher number of LNs was found in moderately differentiated tumors of the laparoscopic group when compared with the open surgery group (16.7 vs. 14.2, P<0.01). The numbers of harvested LNs in the proximal tumors and in stage II and III tumors were higher in the laparoscopic group than in the open group (18.9 vs. 15.4, P<0.001; 17.9 vs. 14.2, P=0.002; 17.3 vs. 15.3, P=0.02, respectively). CONCLUSIONS: Laparoscopic surgery for colorectal cancer can achieve LN retrieval similar to that achieved by the open approach. PMID- 22318058 TI - Laparoscopic colorectal cancer surgery by a colon lifting-up technique that decreases the number of access ports: comparison by propensity scoring of short term and long-term outcomes with standard multiport laparoscopic surgery. AB - BACKGROUND: Laparoscopic colectomy for colorectal cancer has become established as a minimally invasive surgical approach. However, many disposable instruments are required, and there is an associated disadvantage of cost. We have developed a new technique, which uses a suture string to lift up the colon. This method is expected to reduce the number of access ports required without compromising the radical cure. OPERATIVE PROCEDURE: A suture string piercing the abdominal wall is passed through the mesocolon. The colon is retracted anteriorly and is fixed at the abdominal wall. The main mesenteric vessels are under tension, and lymph node dissection is performed easily by a medial approach. The working space is more stable because the colon is fixed to the abdominal wall. METHODS: This study examined the short-term and long-term surgical outcomes of laparoscopic resection for colorectal cancer using our colon lifting-up technique (CLT), compared with the standard multiport technique. The study design was a case-matched control by propensity scoring. Analyzed variables were sex, age, American Society of Anesthesiologists score, cancer in a different organ, multiple colorectal cancer, operator, operative year, tumor location, operative procedure, adjuvant chemotherapy, and International Union Against Cancer TNM stage. RESULTS: From 2000 to 2010, 301 patients underwent CLT and 436 standard multiport technique, 148 patients were matched by propensity score and analyzed. Regarding short-term outcomes, there was no difference between the 2 groups. The mean number of ports needed was 3.37+/-0.48 for CLT (93 with 3 ports, 55 with 4). There were no differences in recurrence-free survival and overall survival in long-term follow up results for each stage. There were neither recurrences nor complications due to CLT. CONCLUSIONS: The CLT facilitated laparoscopic colectomy without compromising cure rates. It is a useful method to keep a stable view and to conserve medical resources. PMID- 22318059 TI - The prevalence and extent of gastroesophageal reflux disease correlates to the type of lung transplantation. AB - BACKGROUND: Evidence is increasingly convincing that lung transplantation is a risk factor of gastroesophageal reflux disease (GERD). However, it is still not known if the type of lung transplant (unilateral, bilateral, or retransplant) plays a role in the pathogenesis of GERD. STUDY DESIGN: The records of 61 lung transplant patients who underwent esophageal function tests between September 2008 and May 2010, were retrospectively reviewed. These patients were divided into 3 groups based on the type of lung transplant they received: unilateral (n=25); bilateral (n=30), and retransplant (n=6). Among these groups we compared: (1) the demographic characteristics (eg, sex, age, race, and body mass index); (2) the presence of Barrett esophagus, delayed gastric emptying, and hiatal hernia; and (3) the esophageal manometric and pH-metric profile. RESULTS: Distal and proximal reflux were more prevalent in patients with bilateral transplant or retransplant and less prevalent in patients after unilateral transplant, regardless of the cause of their lung disease. The prevalence of hiatal hernia, Barrett esophagus, and the manometric profile were similar in all groups of patients. CONCLUSIONS: Although our data show a discrepancy in prevalence of GERD in patients with different types of lung transplantation, we cannot determine the exact cause for these findings from this study. We speculate that the extent of dissection during the transplant places the patients at risk for GERD. On the basis of the results of this study, a higher level of suspicion of GERD should be held in patients after bilateral or retransplantation. PMID- 22318060 TI - Multivariate evaluation of the technical difficulties in performing laparoscopic anterior resection for rectal cancer. AB - BACKGROUND: Although the laparoscopic approach is accepted for the treatment of colon cancer, its value for low rectal cancer is unknown. We sought to evaluate the technical feasibility of laparoscopic low anterior resection (Lap-AR) by determining short-term clinical outcomes and identifying the corresponding predictive factors. METHODS: A retrospective single-institution study was carried out on 82 patients in whom Lap-AR had been attempted for rectal cancer during the period spanning April 2001 to December 2009. Patient characteristics, operative outcomes, and postoperative morbidities and mortalities were analyzed. RESULTS: The median operative time and the intraoperative blood loss were 300 minutes and 72.5 g, respectively. Overall morbidity and mortality rates were 11.0% and 0%, respectively. Complications included wound infection (6.1%, n=5), anastomotic leakage (1.2%, n=1), ileus (1.2%, n=1), and pneumonia (2.4%, n=2). A multivariate analysis indicated that the important risk factor associated with an operative time of >300 minutes was the T factor, and the risk factor associated with intraoperative blood loss was a body mass index (BMI) of >25 kg/m(2). CONCLUSIONS: Lap-AR is a technically feasible, safe, and effective method for treating patients with rectal cancer. A BMI>25 kg/m(2) and the T factor related to operative blood loss and operative time, respectively. Assessment of high BMI and, in particular, advanced tumor depth, should alert surgeons to the increased technical difficulty of Lap-AR. PMID- 22318061 TI - A randomized clinical trial comparing Ligasure versus stapled hemorrhoidectomy. AB - Stapled hemorrhoidectomy (SH) and Ligasure hemorrhoidectomy (LH) are standard for hemorrhoidal disease treatment, but the surgical principle is different. This randomized clinical trial compared the 2 methods. We included 98 patients with grade 3 hemorrhoidal disease: 46 patients treated by SH and 52 patients by LH. Incidence of complications, recurrence, postoperative pain, wound healing time, and time off everyday activity were observed. The follow-up period was 24 months. We found that LH has a significantly shorter wound healing time. The recurrence rate and the overall postoperative complication rate was higher after SH but not significantly (recurrence LH vs. SH: 1.9% vs. 11.1%; complications LH vs. SH: 13.5% vs. 23.9%). Postoperative pain level, analgesic consumption, and time off everyday activity were practically the same in both groups. Both procedures can be used to treat grade 3 hemorrhoidal disease with the same efficacy, but analysis of recurrence after SH is necessary. PMID- 22318062 TI - Pleural abrasion for mechanical pleurodesis in surgery for primary spontaneous pneumothorax: is it effective? AB - PURPOSE: Some patients with primary spontaneous pneumothorax suffer from recurrence of bullous lesions of the lung after resection. Mechanical pleurodesis by pleural abrasion is one of the standard procedures to prevent recurrence. However, there is actually little evidence that pleural abrasion reduces the recurrence of primary spontaneous pneumothorax. Our aim was to evaluate the efficacy of mechanical pleurodesis by pleural abrasion during thoracoscopic procedures for primary pneumothorax. METHODS: From January 2003 to December 2009, 263 patients underwent 294 initial thoracoscopic wedge resections with or without pleural abrasion for primary spontaneous pneumothorax at the Samsung Medical Center. Medical records of patients were reviewed retrospectively. RESULTS: Thirty-one patients were excluded from the study due to various comorbidities. The remaining 232 patients underwent 257 thoracoscopic wedge resections with (165) or without (92) pleural abrasion. No mortality was observed. Seven additional chemical pleurodesis and 3 reoperations were performed due to persistent air leakage after initial surgery. There were 18 instances of recurrence, and the overall recurrence rate was 7.1%. Twelve additional wedge resections were performed because of recurrence after initial surgery. The mean duration of postoperative pleural drainage was 2.86 days. There were no significant differences in the recurrence rate (P=0.9499), and duration of chest tube drainage (P=0.5200) between the patients with and without pleural abrasion. Younger patients, especially below 17 years of age, had significant risk of recurrence (P<0.0001). CONCLUSIONS: Thoracoscopic wedge resection alone successfully controlled primary spontaneous pneumothorax. Additional pleural abrasion did not decrease the recurrence of pneumothorax after wedge resection of bullae for primary spontaneous pneumothorax. Younger age was associated with higher risk of recurrence. PMID- 22318063 TI - Intraoperative endoscopy for the assessment of circular-stapled anastomosis in laparoscopic colon surgery. AB - INTRODUCTION: Anastomotic bleeding after a circular-stapled anastomosis in laparoscopic colon resections is a rare but extremely aggravating complication. An intraoperative endoscopic assessment of the anastomosis allows immediate evaluation regarding bleeding and possible leakage. The aim of the study was to evaluate the impact of routine intraoperative endoscopy on postoperative complications. METHODS: Since May 1999, data of all laparoscopic colon resections were collected in a prospective database. Since July 2007, we assessed every circular-stapled anastomosis with a flexible endoscope for bleeding, integrity of mucosa, and leakage. The patients with (+) and without (-) routine endoscopic assessment were compared regarding postoperative complications. RESULTS: Group(-) consisted of 253 patients [133 male, 120 female; mean age, 60 years (25 to 86 y)] and group(+) consisted of 85 patients [44 male, 41 female; mean age, 62 years (22 to 87 y), P=not significant] In group(-), postoperative anastomotic bleeding was diagnosed in 11 patients (4.3%) and 7 (2.8%) of these patients required endoscopic assessment and clipping. In group(+), endoscopy showed anastomotic bleeding in 5 patients (5.9%) at the time of surgery, which required clipping. Anastomotic leak was observed in 2 patients (2.4%): in one patient the circular staple line was oversewn and in the other patient anastomosis was redone. Two (2.4%) patients in group(+) had postoperative anastomotic bleeding requiring reendoscopy and clipping. The postoperative leakage rate was not significantly different in both the groups [(-)1.6%, (+)1.2%, P= not significant]. CONCLUSIONS: Intraoperative endoscopic assessment of circular-stapled anastomosis can detect early anastomotic bleeding and leakage. Although the postoperative rate of bleeding and leakage was not significantly reduced in our study, we still recommend endoscopic assessment of the circular-stapled anastomosis as a routine procedure in colorectal surgery, as the benefits outweigh the risks. PMID- 22318064 TI - Comparison between endoscope-assisted partial mastectomy with filling of dead space using absorbable mesh and conventional conservative method on cosmetic outcome in patients with stage I or II breast cancer. AB - BACKGROUND: Studies comparing cosmetic outcome between conventional conservative method (CCM) and endoscope-assisted partial mastectomy (EAPM) are scarce. PATIENTS AND METHODS: A total of 111 patients with stage I or II breast cancer who underwent CCM (n=51) or EAPM (n=60) were reviewed. Evaluation of cosmetic outcome consisted of a 3-level scoring method; breast retraction assessment (0 2), nipple deviation (0-2), atrophy (0-2), skin change (0-2), and scar (0-2). Total scores >=7 were considered satisfactory. Score 2 was considered satisfactory for analysis by each scoring criterion. RESULTS: EAPM had a higher rate of satisfactory results compared with CCM (71.7% vs. 52.9%; P=0.042), particularly for atrophy (55.0% vs. 29.4%; P=0.007), and scar (55.0% vs. 31.4%; P=0.012) and for location B (70.0% vs. 12.5%; P=0.025). CONCLUSIONS: EAPM is superior to CCM for postoperative cosmetic outcome with respect to atrophy, scar, and lower tumor location. PMID- 22318065 TI - Psychological and physical stress among experienced and inexperienced surgeons during laparoscopic cholecystectomy. AB - PURPOSE: Surgical procedures are mentally and physically demanding, and stress during surgery may compromise patient safety. We investigated the impact of surgical experience on surgeons' stress levels and how perioperative sleep quality may influence surgical performance. METHODS: Eight experienced and 8 inexperienced surgeons each performed 1 laparoscopic cholecystectomy. Questionnaires measuring perioperative mental and physical strain using validated visual analog scale and Borg scales were completed. Preoperative and postoperative sleep quality of the surgeon was registered and correlated to perioperative strain parameters. RESULTS: Preoperative to postoperative frustration among experienced surgeons was significantly reduced and this was not found in the inexperienced surgeons (visual analog scale: preoperative 13 (2-65) mm, postoperative 4 (0-51) mm vs. preoperative 5(0-10) mm, postoperative 5(1-46) mm; P=0.04). Physical strain was significantly induced in both groups in the upper extremities. Preoperative and postoperative sleep quality was significantly correlated to postoperative mental strain parameters. CONCLUSIONS: Perioperative frustration levels were different among inexperienced and experienced surgeons. Perioperative sleep quality may influence postoperative mental strain and should be considered in studies examining surgeons' stress. PMID- 22318066 TI - Laparoscopic adrenalectomy in children for neuroblastoma: report of case series. AB - BACKGROUND: Neuroblastoma is one of the most common solid tumors in the pediatric population and the adrenal gland is the main abdominal site of this tumor. The laparoscopic approach has become the standard of care for most benign adrenal tumors in adults, but the role of laparoscopic adrenalectomy in children for malignant tumor is still a point of controversy. However, there is a growing experience with laparoscopic neuroblastoma resection of small lesions and the use of minimally invasive techniques for the initial management of infiltrative neuroblastoma in the last years. The aim of this study is to describe our initial experience with laparoscopic adrenalectomy for neuroblastoma in children, based on surgical outcomes. METHODS: A retrospective review of 7 laparoscopic adrenalectomies performed in a single institution between October 2008 and October 2009. We focused our analysis on early surgical outcomes. RESULTS: The mean tumoral size was 2.8+/-0.9 cm, the average surgical time was 138.6+/-65.5 minutes, and the mean hospital stay was 2.9+/-1.6 days. One stage IV patient was submitted to conversion due to bleeding and needed blood transfusion. There were no late complications or deaths and the mean follow-up time was 18.8+/-6.1 months. CONCLUSIONS: The laparoscopic approach for adrenal neuroblastoma resection is feasible in children with good outcomes, but should be reserved to patients with small, well-circumscribed adrenal lesions, without invasive or infiltrative disease. PMID- 22318067 TI - Intraoperative NOTES endosonography and identification of mock hepatic lesions. AB - PURPOSE: Intraoperative ultrasound is commonly used during standard transabdominal surgery. The feasibility of endoscopic ultrasound (EUS) through Natural Orifice Translumenal Endoscopic Surgery (NOTES) for identification of abdominal lesions with a flexible echoendoscope has not been studied. AIM: To test the feasibility of NOTES-EUS for abdominal exploration and identification of mock hepatic lesions. METHODS: Five pigs underwent transvaginal or transcolonic NOTES and endosonographic exploration. In 3 anesthetized pigs, mock hepatic lesions were created and NOTES-EUS was then performed to identify these mock lesions. Necropsy was performed in all cases. RESULTS: All target organs were consistently identified by NOTES-EUS in all animals. Mock hepatic lesions were successfully created in 3 animals and were able to be located by NOTES-EUS. No complications were observed at necropsy. CONCLUSIONS: Abdominal exploration and localization of mock lesions by NOTES-EUS is technically feasible. As natural orifice surgery evolves, intraoperative NOTES-EUS would be an essential addition to the NOTES armamentarium. PMID- 22318068 TI - One port laparoscopic technique for interval placement of intraperitoneal chemotherapy port under direct visualization. AB - PURPOSE: In an effort to minimize catheter-related complications we present a 1 port laparoscopic procedure for interval placement of an intraperitoneal chemotherapy catheter under direct visualization. METHODS: A single 5-mm laparoscopic port is placed in the umbilicus. A 5-cm incision is made in the midaxillary line and a pocket is created to hold the intraperitoneal chemotherapy port. The introducer is then tunneled from the pocket towards the umbilicus and is used to pierce the fascia under direct visualization. It is then tunneled towards the camera and removed through the umbilical port. The catheter is cut and allowed to fall back into the abdomen under direct visualization. RESULTS: No patient had their chemotherapy regimen altered because of catheter-related complications. Specifically, there were no other infections, leakage, blockage, or access problems. CONCLUSIONS: In selected patients, this may be considered as a new minimally invasive option. PMID- 22318069 TI - Laparoscopy-assisted distal gastrectomy in a patient with early gastric cancer and polysplenia. AB - A 44-year-old woman is presented who was referred for further evaluation and surgical treatment of gastric cancer detected on a routine health evaluation. Endoscopic examination with biopsy revealed about a 1-cm early gastric cancer of signet-ring cell type at the lesser curvature side of the antrum. A computed tomography scan of the abdomen confirmed the findings of intestinal malrotation, polysplenia, and a large enhancing mass in the uterus. The results of blood testing and echocardiography were within normal limits. The patient underwent laparoscopy-assisted distal gastrectomy and transvaginal hysterectomy for early gastric cancer and uterine myoma. A lobulated spleen in several parts, intestinal malrotation, and a very large uterine mass were identified during the laparoscopic surgery. The postoperative course was uneventful. This case illustrates the importance of thorough preoperative anatomic assessment, especially for laparoscopic surgery in patients with anatomic abnormalities. PMID- 22318070 TI - Laparoscopic diagnosis and management of an acute jejunal diverticulitis. AB - Jejunal diverticulitis is a rare clinical entity with a high degree of clinical variability and nonspecific radiographic findings, making it a diagnostic challenge. Definitive diagnosis is typically not made until surgery is undertaken, most commonly by laparotomy. We present a case of laparoscopic diagnosis and management of an elderly man with an acute jejunal diverticulitis. The use of a laparoscopic approach provided for an effective therapy without any perioperative morbidity. Clear visualization of the extent of the disease allowed us to avoid intestinal resections. Laparoscopic washout and postoperative bowel rest and intravenous antibiotics seem to be sufficient for acute nonperforated jejunal diverticulitis. Despite his advanced age, our management allowed for a speedy and uneventful recovery in our patient. As a result, we advocate that diagnostic laparoscopy should be considered in most cases of suspected acute jejunal diverticulitis. In addition to facilitating a correct diagnosis, laparoscopic exploration and washout may provide effective management of the acute attack while obviating the need for major abdominal explorations and resections. PMID- 22318071 TI - Laparoscopic management of gastric angiomyolipoma: case report and review of literature. AB - Angiomyolipoma of stomach is extremely rare. Only 1 case has been reported earlier. We report a case of 40-year-old female who presented with gastrointestinal bleeding. Upper gastrointestinal endoscopy suggested a polypoidal growth in the stomach. Biopsy from the growth was suggestive of mesenchymal tumor. The contrast-enhanced computed tomography of abdomen revealed a pedunculated 4*3 cm, intramural lesion at the junction of first and second parts of duodenum, likely lipoma. The stalk seemed to be arising from distal stomach. At laparoscopy, a highly mobile lesion was observed arising from the posterior wall of stomach. Wedge resection of the lesion was performed laparoscopically after doing an anterior gastrotomy. The final diagnosis on histopathology was a gastric angiomyolipoma. PMID- 22318072 TI - Pseudoaneurysm of the inferior epigastric artery: a rare complication of laparoscopic ventral hernia repair. AB - Pseudoaneurysm of the inferior epigastric artery (IEA) is a recognized complication of surgery; however, it is a very rare clinical occurrence. The anatomic position of the IEA subjects patients to possible IEA injury during abdominal wall procedures that are close to the artery, such as insertions of drains, Tenckhoff catheters, laparoscopic trocars, or paracentesis. Treatment options include open surgery, percutaneous coil embolization, embolization with N butyl cyanoacrylate, sonographic-guided thrombin injection, or sonographic-guided compression. We report the first case of a pseudoaneurysm arising from the IEA after a laparoscopic ventral hernia repair. To our knowledge, 17 IEA pseudoaneurysms have been reported, only 3 of which were spontaneous. The pseudoaneurysm in our patient was successfully treated by percutaneous injection of thrombin by interventional radiology. PMID- 22318073 TI - Laparoscopic repair of a left paraduodenal hernia presenting with acute bowel obstruction: report of a case. AB - An internal hernia is any protrusion of a solid organ or a hollow viscus through a defect within the abdominal cavity. Paraduodenal hernias (PDHs) are rare; however, they are the most common form of internal hernias. We present a case of a left PDH in a 59-year-old healthy woman who presented with acute bowel obstruction. The PDH was diagnosed preoperatively using computed tomography scan. Laparoscopic exploration of the abdomen was then performed for reduction of the hernia. Using this approach, we managed to close the defect with intracorporeal continuous suturing with the aim of avoiding future incarceration. The patient was discharged 60 hours postoperation in a good condition, compared with 3 to 28 days postoperation reported in most of the literature. Our search of the english language literature revealed only 16 reported cases of laparoscopic repair of PDH. We believe that laparoscopic treatment of PDH in experienced hands is recommended in selected cases as it decreases the morbidity and significantly shortens the hospital stay. PMID- 22318074 TI - Periappendiceal abscess mimicking appendiceal cancer. AB - Appendiceal cancer was strongly suspected in this case because of its unique colonoscopic, radiologic, and intraoperative presentation. Hence, laparoscopic enbloc right hemicolectomy and peritonectomy were performed. The diagnosis of periappendiceal abscess was confirmed later after the operation. Appendiceal disease is hard to differentiate because of the wide spectrum of differential diagnosis. So, when there is a strong suspicion of appendiceal cancer, laparoscopic right colectomy, which is minimally invasive and potentially curative can be the treatment of choice. PMID- 22318075 TI - Trocar site hernia after the use of 12-mm bladeless trocar in robotic colorectal surgery. AB - Bladeless trocar decreases accidental injuries and incisional hernia; further a closure of fascial defect is considered to be unnecessary if a 12-mm bladeless trocar is used at nonmidline. We present a case of bowel herniation after using 12-mm bladeless trocar in robotic colorectal surgery. A 67-year-old woman had rectal cancer and underwent a robot-assisted low anterior resection. The facial defect after using 12-mm bladeless trocar was closed with the routine procedure. On postoperative day 7, her hernia of the trocar site was diagnosed by an abdominal computed tomography. The herniation was reduced with laparoscopic surgery. In conclusion, a trocar site hernia can occur after using a 12-mm bladeless trocar in robotic surgery. PMID- 22318076 TI - Laparoscopic management of pseudocyst of the pancreas in a pregnant patient. AB - Gallstone pancreatitis is a rare problem in pregnant patients. A primigravida with persistent symptoms of abdomen pain, nausea, vomiting, and inability to tolerate oral diet presented at 5 weeks of pregnancy. A laparoscopic cystogastrostomy with cholecystectomy was performed at 13 weeks of pregnancy. There are only 10 case reports in literature of pseudocyst in pregnancy and in none of them ante partum surgical management was done. PMID- 22318077 TI - Laparoscopic diverticulectomy for massive hemorrhage in a duodenal diverticulum. AB - Hemorrhagic duodenal diverticula are rare and are treated by endoscopy or open diverticulectomy, especially when there is a massive hemorrhage. We report what we believe to be the first instance of urgent laparoscopic diverticulectomy of a large, inflamed duodenal diverticulum with massive hemorrhage. An elderly patient had a screening colonoscopy and additional upper gastrointestinal endoscopy because of vague upper gastrointestinal symptoms; however, both were reported to be normal. She subsequently developed massive hematemesis. Clinical examination revealed a tender right upper quadrant mass and imaging confirmed a large duodenal diverticulum with surrounding inflammatory changes. Urgent laparoscopic diverticulectomy was performed with an uneventful recovery and follow-up. Laparoscopic diverticulectomy should be considered in managing hemorrhagic duodenal diverticula. PMID- 22318078 TI - A severe case of xanthogranulomatous cholecystitis along with a review of CT indications for nonoperative management including percutaneous drainage. AB - BACKGROUND: Xanthogranulomatous cholecystitis is a rare but severe presentation of cholecystitis characterized by extensive inflammation of the gallbladder wall with characteristic histopathological features. Frequently, the inflammatory mass resembles gallbladder cancer macroscopically, which further complicates therapeutic decisions. CASE PRESENTATION: We report a case of xathogranulomatous cholecystitis with characteristic computed tomography findings, which was managed by percutaneous drainage of the gallbladder, giving the opportunity for a delayed elective cholocystectomy with an excellent postoperative outcome. DISCUSSION: Recent studies give emphasis on certain criteria for the differential diagnosis of xanthogranulomatous cholecystitis against carcinoma. Characteristic computed tomography features are usually sufficient to establish the diagnosis with safety and decide a nonoperative management of the disease in the acute phase. Percutaneous gallbladder drainage is regarded as a safe and an efficient method for the initial treatment of severe cases. PMID- 22318079 TI - Pyoderma gangrenosum postlaparoscopy: a rare complication. AB - Pyoderma gangrenosum (PG) is a rare, chronic, often destructive, inflammatory skin disease in which a painful nodule or pustule breaks down to form a progressively enlarging ulcer. There are only 4 reported cases of postlaparoscopic PG and the purpose of this case report is to describe a patient found to have the disease after elective laparoscopy. Although rare, the occurrence of PG after surgery, even where incisions are small such as in laparoscopic surgery, is a diagnosis that cannot be neglected, especially due to the high morbidity, which increases if the diagnosis is not made and the patient is subjected to debridement. PMID- 22318080 TI - Alternative salvage technique for removing large sharp foreign body near upper esophageal sphincter. AB - Removing sharp foreign bodies located in the esophagus can be dangerous and challenging. Proper apparatus and appropriate technique should be employed to avoid life-threatening complications such as perforation and mediastinitis. A 59 year-old man came to the emergency department with foreign body sensation in the upper esophagus which proved to be a large sharp fish bone impacted near upper esophageal sphincter. With the ordinary upper endoscope, the foreign body could not be retrieved even with the assistance of a cap. Foreign body removal was attempted again using a colonoscope with cap fitted at the end. Larger caliber of the scope rendered more stable support within the lumen enabling better maneuver of the scope tip to secure wider working space, and application of the cap permitted better visual field. Herein, we report the first case of successful removal of a large sharp fish bone impacted near the upper esophageal sphincter using cap assisted colonoscope. PMID- 22318081 TI - Laparoscopic hybrid NOTES liver resection for metastatic colorectal cancer. AB - BACKGROUND: Abdominal wound extraction site continues to be a major source of morbidity after laparoscopic-assisted surgery. METHODS: A 59-year-old African American woman with a past history of T3N2M1 colon cancer, who underwent laparoscopic sigmoid colectomy and wedge liver resection (segment IV A) followed by adjuvant chemotherapy was our subject for this study. Twelve months later, she was found to have a positron emission tomography positive liver lesion of 6.5 cm at the left lateral liver segment. A combined laparoscopic-transvaginal approach was used. Four 5-mm trocars were used. The liver parenchyma was divided using the harmonic scalpel, whereas the left hepatic vein was transected using the laparoscopic transvaginal vascular stapler. The specimen was placed in an endobag and extracted transvaginally. The specimen size was 14*8*3.5 cm and that of the lesion was 6.5*5.7*4 cm. The patient was discharged on postoperative day 2. RESULTS: Operative time was 120 minutes and blood loss was minimal. The patient was discharged on postoperative day 2. No postoperative complications were found after 30 days. CONCLUSIONS: Laparoscopic-assisted natural orifice transluminal endoscopic surgery results in quicker recovery, less postoperative pain, and potential wound-related complications. This technique is safe and effective with excellent aesthetic results. (Video, Supplemental Digital Content 1, http://links.lww.com/SLE/A54). PMID- 22318082 TI - Retroperitoneal minimally invasive pancreatic necrosectomy using single-port access. AB - Infected pancreatic necrosis is a life-threatening complication of acute pancreatitis that has been traditionally managed with open surgical debridement. Over the last decade, minimally invasive techniques have been increasingly used for the treatment of infected pancreatic necrosis and their results are encouraging. Percutaneous retroperitoneal pancreatic necrosectomy is one of the minimally invasive approaches used for debridement of pancreatic necrosis. We report our technique of retroperitoneoscopic necrosectomy using a single-port access. PMID- 22318083 TI - Impact of the herbicide (RS)-MCPP on an anaerobic membrane bioreactor performance under different COD/nitrate ratios. AB - The degradation of (RS)-MCPP was investigated in an anaerobic membrane bioreactor (AnMBR) using nitrate as an available electron acceptor under different COD/NO(3)(-)-N ratios. Results showed high soluble COD removal efficiency (80 93%) when the reactor was operated at high COD/NO(3)(-)-N ratios. However, the COD removal started to decline (average 15%) at high nitrate concentrations coinciding with a drop in nitrate removal efficiency to 37%, suggesting that the denitrification activity dropped and affected the AnMBR performance when nitrate was the predominant electron acceptor. Additionally, the removal efficiency of (RS)-MCPP increased from 2% to 47% with reducing COD/NO(3)(-)-N ratios, whilst the (RS)-MCPP specific utilisation rate (SUR) was inversely proportional to the COD/NO(3)(-)-N ratio, suggesting that a lower COD/NO(3)(-)-N ratios had a positive influence on the (RS)-MCPP SUR. Although nitrate had a major impact on methane production rates, the methane composition was stable (approximately 80%) for COD/NO(3)(-)-N ratios of 23 or more. PMID- 22318084 TI - Fermentative biohydrogen production from lactate and acetate. AB - In this study, a continuous-flow stirred tank reactor (CSTR) fed with lactate and acetate was operated to enrich hydrogen-producing bacteria. By varying the influent substrate concentrations and hydraulic retention times (HRT), the volumetric loading rate (VLR) of 55.64 kg-COD/m(3)/day seemed to be optimum for this enriched culture for fermentative hydrogen production from lactate and acetate. The results of batch experiments confirmed that the enriched culture tended to fulfill the e(-) equiv requirement for cell growth at a lower VLR condition (21.77 kg-COD/m(3)/day), while it could largely distribute the e(-) equiv for hydrogen production at a higher VLR condition. However, a maximum lactate/acetate concentration allowed for enriching this culture existed, especially at a lower HRT condition in which wash-out can be an issue for this enriched culture. Finally, the results of cloning and sequencing indicated that Clostridium tyrobutyricum was considered the major hydrogen-producing bacteria in the CSTR fed with lactate and acetate. PMID- 22318085 TI - [Primary hepatic carcinoid tumor: an unusual localization]. PMID- 22318086 TI - [Need for coordinated, multidisciplinary care in the Spanish population at elevated risk of colorectal cancer]. PMID- 22318087 TI - Responsibility Without Blame: Empathy and the Effective Treatment of Personality Disorder. AB - Effective treatment of personality disorder (PD) presents a clinical conundrum. Many of the behaviors constitutive of PD cause harm to self and others. Encouraging service users to take responsibility for this behavior is central to treatment. Blame, in contrast, is detrimental. How is it possible to hold service users responsible for harm to self and others without blaming them? A solution to this problem is part conceptual, part practical. I offer a conceptual framework that clearly distinguishes between ideas of responsibility, blameworthiness, and blame. Within this framework, I distinguish two sorts of blame, which I call 'detached' and 'affective.' Affective, not detached, blame is detrimental to effective treatment. I suggest that the practical demand to avoid affective blame is largely achieved through attention to PD service users' past history. Past history does not eliminate responsibility and blameworthiness. Instead, it directly evokes compassion and empathy, which compete with affective blame. PMID- 22318088 TI - Decentralised water systems: emotional influences on resource decision making. AB - The study of emotion has gathered momentum in the field of environmental science, specifically in the context of community resource decision-making. Of particular interest in this review is the potential influence of emotion, risk and threat perception on individuals' decisions to acceptance and adopt decentralised water systems, such as rainwater tanks and greywater systems. The role of message framing is also considered in detail, as well as the influences that different types of framing can have on decision making. These factors are considered as possible predictors for analysing community acceptance of decentralised water in urban environments. Concepts believed to be influenced by emotion, such as trust and framing, are also discussed as potentially meaningful contributors to an overall model of community acceptance of decentralised water. Recommendations are made for how emotion-based concepts, such as risk and threat, can be targeted to facilitate widespread adoption of decentralised systems and how researchers can explore different types of emotions that influence decision making in distinct ways. This review is an important theoretical step in advancing the psycho-social understanding of acceptance and adoption of on-site water sources. Avenues for future research are recommended, including the need for greater theoretical development to encourage future social science research on decentralised systems. PMID- 22318089 TI - Zinc finger nucleases: looking toward translation. AB - Genetic engineering has emerged as a powerful mechanism for understanding biological systems and a potential approach for redressing congenital disease. Alongside, the emergence of these technologies in recent decades has risen the complementary analysis of the ethical implications of genetic engineering techniques and applications. Although viral-mediated approaches have dominated initial efforts in gene transfer (GT) methods, an emerging technology involving engineered restriction enzymes known as zinc finger nucleases (ZFNs) has become a powerful new methodology for gene editing. Given the advantages provided by ZFNs for more specific and diverse approaches in gene editing for basic science and clinical applications, we discuss how ZFN research can address some of the ethical and scientific questions that have been posed for other GT techniques. This is of particular importance, given the momentum currently behind ZFNs in moving into phase I clinical trials. This study provides a historical account of the origins of ZFN technology, an analysis of current techniques and applications, and an examination of the ethical issues applicable to translational ZFN genetic engineering in early phase clinical trials. PMID- 22318090 TI - Potent antitumor activity of oncolytic adenovirus-mediated SOCS1 for hepatocellular carcinoma. AB - Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in diverse cancers, which contributes to the proliferation and survival of cancer cells by upregulating apoptosis inhibitors and cell cycle regulators. Suppressor of cytokine signaling 1 (SOCS1) is an important negative regulator of STAT pathways and is frequently silenced in many types of cancers. In this study, we used oncolytic adenoviral vector to deliver SOCS1 gene (AdCN305-SOCS1) to treat hepatocellular carcinoma (HCC). Our data showed that SOCS1 was downregulated in HCC cells by hypermethylation. AdCN305-SOCS1 was found selectively replicated, which led to SOCS1 overexpression in HCC cells. Infection of HCC cells with AdCN305-SOCS1 resulted in inhibition of STAT3 phosphorylation and downregulation of survivin, cyclin D1, Bcl-xL and C-myc. AdCN305-SOCS1 exhibited strong cytotoxicity to HCC cells by inducing apoptosis in vitro and in vivo. This study suggests that transfer of SOCS1 by an oncolytic adenovirus may be a potent antitumor approach for cancer therapy. PMID- 22318091 TI - Combination gene therapy targeting on interleukin-1beta and RANKL for wear debris induced aseptic loosening. AB - This study investigated the efficacy of a combination gene therapy to repress interleukin-1 (IL-1) and receptor activator of nuclear factor NF-kappa B ligand (RANKL) for the treatment of particulate debris-induced aseptic loosening, and tried to explore the molecular mechanism of the exogenous gene modifications on osteoclastogenesis. RAW cells activated by titanium particles were transduced with DFG-IL-1Ra (retroviral vector encoding IL-1 receptor antagonist) and AAV-OPG (adeno-associated viral vectors-osteoprotegerin) individually or in combination for 4 weeks. Pro-inflammatory cytokines in culture media were determined by enzyme-linked immunosorbent assay, and gene expressions of RANK, IL-1beta, c-Fos, TRAF6, JNK1 and CPK were examined using real-time PCR. An established knee implant-failure mouse model was employed to evaluate the efficacy of the in vivo double-gene therapy. The surgical implantation of a titanium alloy pin into the proximal tibia was followed by monthly challenge with titanium debris. Peri implant gene transfers of IL-1Ra and OPG (respectively or in combination) were given 3 weeks after surgery. The combination of OPG and IL-1Ra gene transfer exhibited strong synergetic effects in blockage of inflammation and osteoclastogenesis at 8 weeks after gene modification. The combination therapy reversed peri-implant bone resorption and restored implant stability when compared with either single gene transduction. Real-time PCR data indicated that the action of IL-1Ra gene therapy may be mediated via the JNK1 pathway, while the reduction of osteoclastogenesis by OPG gene modification may be regulated by c Fos expression. In addition, both gene modifications resulted in significant diminishment of TRAF6 expression. PMID- 22318093 TI - The association of chronic kidney disease with brain lesions on MRI or CT: a systematic review. AB - BACKGROUND AND PURPOSE: This review reports on the association between chronic kidney disease (CKD) established with glomerular filtration rate (GFR) and brain lesions established with MRI or CT. METHODS: Literature was searched combining synonyms of kidney function, brain lesions and terms for the definitions thereof, and MRI or CT. This resulted in 1507 articles, of which 20 were finally included. RESULTS: Cross-sectional studies found an association between GFR and white matter lesions (WML) with 7 out of 11 associations significant (odds ratios (OR) GFR, continuous variable: 0.84-0.89 per 10 ml/min/1.73 m(2)). Most significant results were found in studies including subjects from the general population. GFR was associated with silent cerebral infarcts (SCI) with 9 out of 12 associations significant (OR GFR, continuous variable: 0.96-0.99 per ml/min/1.73 m(2)). Brain atrophy was reported significant 4 out of 5 associations (OR GFR, continuous variable: 0.64 per 10 ml/min/1.73 m(2)). Additionally, 2 follow up studies were included. One established that serum creatinine at baseline is a significant predictor of the presence of SCI; the other that the presence of SCI at baseline is a significant predictor of a decrease in GFR. CONCLUSION: The results from this review show that CKD is associated with brain lesions. These brain lesions include WML, SCI and brain atrophy. This finding is of clinical importance because these brain lesions are predictive of stroke, cognitive decline and dementia. Additional follow up studies should be performed to better understand the causative pathway and to establish whether screening and preventive programs are beneficial. PMID- 22318092 TI - Progress in gene therapy of dystrophic heart disease. AB - The heart is frequently afflicted in muscular dystrophy. In severe cases, cardiac lesion may directly result in death. Over the years, pharmacological and/or surgical interventions have been the mainstay to alleviate cardiac symptoms in muscular dystrophy patients. Although these traditional modalities remain useful, the emerging field of gene therapy has now provided an unprecedented opportunity to transform our thinking/approach in the treatment of dystrophic heart disease. In fact, the premise is already in place for genetic correction. Gene mutations have been identified and animal models are available for several types of muscular dystrophy. Most importantly, innovative strategies have been developed to effectively deliver therapeutic genes to the heart. Dystrophin-deficient Duchenne cardiomyopathy is associated with Duchenne muscular dystrophy (DMD), the most common lethal muscular dystrophy. Considering its high incidence, there has been a considerable interest and significant input in the development of Duchenne cardiomyopathy gene therapy. Using Duchenne cardiomyopathy as an example, here we illustrate the struggles and successes experienced in the burgeoning field of dystrophic heart disease gene therapy. In light of abundant and highly promising data with the adeno-associated virus (AAV) vector, we have specially emphasized on AAV-mediated gene therapy. Besides DMD, we have also discussed gene therapy for treating cardiac diseases in other muscular dystrophies such as limb-girdle muscular dystrophy. PMID- 22318094 TI - Bone loss associated with prevention of breast cancer. PMID- 22318096 TI - Child abuse and neglect: Asia Pacific Conference and the Delhi Declaration. PMID- 22318095 TI - Bone density and structure in healthy postmenopausal women treated with exemestane for the primary prevention of breast cancer: a nested substudy of the MAP.3 randomised controlled trial. AB - BACKGROUND: Exemestane can prevent breast cancer in postmenopausal women. Because of potential widespread use, we examined the safety of exemestane on bone health. METHODS: In this nested safety substudy of the MAP.3 trial (a randomised, placebo controlled, double-blind trial of exemestane 25 mg a day for the primary prevention of breast cancer), we included postmenopausal women from five centres who were eligible to participate in MAP.3, not osteoporotic, not receiving drugs for bone-related disorders, with baseline lumbar spine, total hip, and femoral neck T-scores above -2.0. The primary endpoint was percent change from baseline to 2 years in total volumetric bone mineral density (BMD) at the distal radius by high-resolution peripheral quantitative CT. The primary analysis was per protocol using a non-inferiority margin. This analysis was done earlier than originally planned because of the impending announcement of MAP.3 results and subsequent unmasking of patients to treatment assignment. This study is registered with ClinicalTrials.gov, number NCT01144468, and has been extended to 5 years of unmasked follow-up. FINDINGS: 351 women (176 given exemestane, 175 given placebo; median age 61.3 years [IQR 59.2-64.9]) met our inclusion criteria and completed baseline assessment. At the time of clinical cutoff, 242 women had completed 2 year follow-up (124 given exemestane, 118 given placebo). From baseline to 2 years, the mean percent change in total volumetric BMD at the distal radius was 6.1% (95% CI -7.0 to -5.2) in the exemestane group and -1.8% (-2.4 to -1.2) in the placebo group (difference -4.3%, 95% CI -5.3 to -3.2; p<0.0001). The lower limit of the 95% CI was lower than our non-inferiority margin of negative 4% (one sided test for non-inferiority p=0.70), meaning the hypothesis that exemestane was inferior could not be rejected. At the distal tibia, the mean percent change in total volumetric BMD from baseline to 2 years was -5.0% (95% CI -5.5 to -4.4) in the exemestane group and -1.3% (-1.7 to -1.0) in the placebo group (difference -3.7%, 95% CI -4.3 to -3.0; p<0.0001). The mean percent change in cortical thickness was -7.9% (SD 7.3) in the exemestane group and -1.1% (5.7) in the placebo group at the distal radius (difference -6.8%, 95% CI -8.5 to -5.0; p<0.0001) and -7.6% (SD 5.9) in the exemestane group and -0.7% (4.9) in the placebo group at the distal tibia (difference -6.9%, -8.4 to -5.5; p<0.0001). Decline in areal BMD, as measured by dual-energy x-ray absorptiometry, in the exemestane group compared with the placebo group occurred at the lumbar spine ( 2.4% [95% CI -3.1 to -1.7] exemestane vs -0.5% [-1.1 to 0.2] placebo; difference 1.9%, 95% CI -2.9 to -1.0; p<0.0001), total hip (-1.8% [-2.3 to -1.2] exemestane vs -0.6% [-1.1 to -0.1] placebo; difference -1.2%, -1.9 to -0.4; p=0.004), and femoral neck (-2.4% [-3.2 to -1.7] exemestane vs -0.8% [-1.5 to 0.1] placebo; difference -1.6%, -2.7 to -0.6; p=0.002). INTERPRETATION: 2 years of treatment with exemestane worsens age-related bone loss in postmenopausal women despite calcium and vitamin D supplementation. Women considering exemestane for the primary prevention of breast cancer should weigh their individual risks and benefits. For women taking exemestane, regular bone monitoring plus adequate calcium and vitamin D supplementation are important. To assess the effect of our findings on fracture risk, long-term follow-up is needed. FUNDING: Canadian Breast Cancer Research Alliance (Canadian Institutes of Health Research/Canadian Cancer Society). PMID- 22318097 TI - Iron deficiency, febrile seizures and brain development. PMID- 22318098 TI - Childhood mood disorders: myth or reality. PMID- 22318099 TI - The ignominy of low birth weight in South Asia. PMID- 22318100 TI - Clofibrate for unconjugated hyperbilirubinemia in neonates: a systematic review. AB - OBJECTIVE: To evaluate the effect of clofibrate for unconjugated hyperbilirubinemia in neonates. METHODS: A systematic review with meta-analysis of randomized controlled trials or quasi-randomized controlled trials was conducted to evaluate the clofibrate treatment in neonates with unconjugated hyperbilirubinemia. We followed the guidelines from the Cochrane review group and the PRISMA statement. RESULTS: Of 148 studies identified, a total of 13 studies on 867 infants were included. A single oral administration of clofibrate was associated with decreased need of phototherapy (RR:.38, 95% CI: 0.21 to 0.68), shortened duration of phototherapy (mean duration: 23.88 h, 95% CI: 33.03 to 14.72 h) and reduced peak total serum bilirubin (mean duration: -1.62 mg/dL, 95% CI: 2.13 to -1.11 mg/dL). These effects were especially obvious in term infants and infants without hemolytic diseases. Data regarding mortality or kernicterus were not available from included studies. CONCLUSIONS: Clofibrate may have short term benefits for the infants with hyperbilirubinaemia, especially for population of term infants and infants without hemolytic diseases. Large RCTs with long-term followup are required to verify the safety of clofibrate and assess its long-term effects. PMID- 22318101 TI - Tick induced facial palsy. AB - We report a 3-year old boy with acute onset of left sided facial palsy secondary to tick infestation in the left ear. On 7th day of follow-up, following tick removal, the facial palsy had resolved. PMID- 22318102 TI - Microvillous inclusion disease diagnosed by gastric biopsy. AB - Protracted diarrhea in neonates is uncommon and usually requires an intestinal biopsy for etiological diagnosis. Gastric biopsy has not been used in the routine diagnosis of this condition. We report the first documented patient with microvillous inclusion disease from India, where the diagnosis was established by a gastric biopsy. PMID- 22318103 TI - Venovenous hemodiafiltration and hypothermia for treatment of cerebral edema associated with hyperammonemia. AB - We report a 50 hour old newborn with inborn urea cycle disorder and hyperammonia of 2320 umol/L. The pharmacological treatment of the first metabolic crisis was combined with venovenous hemodiafiltration and therapeutic hypothermia to rescue the patient from a life-threatening cerebral edema. PMID- 22318104 TI - Infantile systemic hyalinosis. AB - Infantile systemic hyalinosis is a rare disorder characterized by widespread deposition of hyaline. They usually present with skin lesions, joint contractures, and intractable diarrhea. We report a 2 year 4 month old boy with growth retardation, typical facial appearance, gingival enlargement, generalized stiff skin, joint contractures, and intermittent diarrhea. Skin biopsy revealed deposition of hyaline. PMID- 22318105 TI - Fenestrated angiocatheter for extensive subcutaneous emphysema. AB - A minimally invasive technique using fenestrated angiocatheters has been described in adult literature for the treatment of extensive subcutaneous emphysema. Here we report a 30 month old infant who developed extensive subcutaneous emphysema and pneumomediastinum, which was relieved by application of microdrainage catheters. PMID- 22318106 TI - Disseminated rhabdomyosarcoma presenting as hypercalcemia. AB - Hypercalcemia may be seen in children with malignancy. We report a 4 year old child with rhabdomyosarcoma that initially presented with signs of hypercalcemia and bone involvement. PMID- 22318107 TI - An unusual cause of acute confusional state. PMID- 22318108 TI - Unusual cause of neonatal respiratory distress. PMID- 22318109 TI - Tetanus vaccine in UIP in India. PMID- 22318111 TI - Unusual reason for chronic musculoskeletal pain. PMID- 22318112 TI - Community based newborn care. PMID- 22318114 TI - Whole body cooling in newborn infants with perinatal asphyxial encephalopathy. PMID- 22318116 TI - Cutaneous Langerhans cell histiocytosis. PMID- 22318117 TI - Angiokeratoma circumscriptum neviforme. PMID- 22318118 TI - Occupational therapy and sensory integration for children with autism: a feasibility, safety, acceptability and fidelity study. AB - OBJECTIVE: To examine the feasibility, safety, and acceptability of a manualized protocol of occupational therapy using sensory integration principles for children with autism. METHODS: Ten children diagnosed with autism spectrum disorder ages 4-8 years received intensive occupational therapy intervention using sensory integration principles following a manualized protocol. Measures of feasibility, acceptability and safety were collected from parents and interveners, and fidelity was measured using a valid and reliable fidelity instrument. RESULTS: The intervention is safe and feasible to implement, acceptable to parents and therapist, and therapists were able to implement protocol with adequate fidelity. These data provide support for implementation of a randomized control trial of this intervention and identify specific procedural enhancements to improve study implementation. PMID- 22318119 TI - Quality of life of caregivers of children with autism in Qatar. AB - INTRODUCTION: Caring for a child diagnosed with autism could affect the quality of life of the caregiver in various different ways. No previous research has assessed the quality of lives of caregivers of children with autism in Qatar. METHODS: Caregivers of a child with autism between 3 and 17 years old were recruited from child rehabilitation clinics in Qatar. The non-autism group was represented by caregivers of a typically growing child visiting a primary health care facility for a routine medical examination. Data collected from both groups included demographic and quality of life information for caregivers. RESULTS: A total of 98 participants consented to take part in the study. Fifty-six of these were caregivers of a child with autism and 42 were caregivers of a typically growing child. There was no significant difference between quality of life domains between the two groups of caregivers, but caregivers of autistic children rated their health as poor and likely to get worse (p < 0.05). CONCLUSIONS: This study provided some evidence for the impact of caring for a child with autism on the life of the caregiver. The findings should help health policy-makers in Qatar to provide better and more focused support to children with autism and their caregivers. PMID- 22318120 TI - Preparation of core-shell CaCO3 capsules via Pickering emulsion templates. AB - Micron size and food grade pristine CaCO(3) particles were used to stabilize an oil in water Pickering emulsion. The particles also acted as nucleation sites for the subsequent crystallization of CaCO(3) with the addition of CaCl(2) and CO(2) gas as precursors. After the controllable crystallization process, a dense CaCO(3) shell with a few microns in thickness was formed. The CaCO(3) shell was proven to be calcite without the presence of crystallization modifiers. The crystallization speed and the shell integrity were controlled by manipulating the addition of CaCl(2) amount during the different crystallization stages; therefore, the homogeneous nucleation in the bulk was almost inhibited, and the heterogeneous nucleation at the oil-water interface on pristine CaCO(3) particles was the main contribution to the growth of the shell. The encapsulated limonene flavor in CaCO(3) capsules showed a prolonged release in neutral water at 85 degrees C, while a burst release at pH 2 water as expected. The method is a simple and scalable process for creating inorganic core-shell capsules and can be used for producing food grade capsules for controlling the flavor release or masking undesirable taste in mouth. PMID- 22318121 TI - Rapid clearance of supplemented tetrahydrobiopterin is driven by high-capacity transporters in the kidney. AB - Tetrahydrobiopterin (BH(4)) is an essential cofactor of aromatic amino acid hydroxylases and NO synthase. Supplementation of BH(4) potentially targets cardiovascular dysfunction as well as inherited BH(4) deficiencies and BH(4) responsive phenylketonuria. However, the high cost/effect ratio of the recommended daily dose of BH(4) supplementation acts against further popularization of this therapy. The aim of this study was to attenuate urinary excretion with the intention of improving efficacy of BH(4) supplementation. The rapid excretion of BH(4) in the urine was confirmed to be the major route of supplemented BH(4) loss. In addition to glomerular filtration into the urine, a dominant rapid exclusion by renal secretion was observed in rats (T((1/2))=16 min) when the plasma BH(4) was higher than about 1 nmol/mL (more than 10 times higher than normal), due to BH(4) supplementation. The rapidity of the process was slowed by prior administration of cyclosporin A, a representative anti excretory drug, and the excretion decelerated to a moderate rate (T((1/2))=53 min). By the combined administration of BH(4) plus cyclosporin A, the blood BH(4) levels were dramatically elevated. It was hypothesized that the drug interfered with kidney excretion of BH(4) rather than by attenuating organ tissue distribution by inhibiting biopterin uptake from the plasma. Consistent with this hypothesis, biopterin levels after BH(4) administration were elevated in major organs in the presence of anti-excretory drugs without notable change in their BH(4) fraction which was consistently 95% or higher regardless of combined administration with the drugs. Targeting these putative transporters would be a promising approach for improving the efficiency of BH(4) supplementation therapy. PMID- 22318122 TI - Alteration of the cerebral zinc pool in a mouse model of Alzheimer disease. AB - Synaptic vesicle Zn is regulated by zinc transporter 3 (ZnT3) and is involved in neurotransmission and synaptic plasticity. Here, we describe extensive alterations of ZnT3-regulated Zn pools in the brains of human amyloid precursor protein-transgenic (Tg2576) mice. In contrast to wild-type littermates in which ZnT3 expression and synaptic Zn increased with age, there were age-dependent reductions in ZnT3 expression and synaptic Zn levels in the hippocampal mossy fiber area of Tg2576 mice. In these mice, a novel Zn pool and ZnT3 expression were colocalized and appeared along dystrophic neurites surrounding compact amyloid plaques that were identified by in situ blue fluorescence, congophilic birefringence, and Abeta42 immunoreactivity. Zn-specific histofluorescence and ZnT3 immunofluorescence in dystrophic neurites were also colocalized with the delta-subunit of adaptor protein complex 3, lysosome-associated membrane protein, cathepsin D, and neurofilament-containing hyperphosphorylated paired helical filaments. The synaptic vesicle marker protein synaptophysin and vesicle associated membrane protein were not found in these neurites, suggesting a role of ZnT3 distinct from itsnormal role in synaptic Zn. ZnT3 immunoreactivity and Zn histofluorescence were also evident in activated astrocytes. These datasuggest that extensive modifications of the cerebral Zn pool, particularly synaptic Zn, may underlie neuronal dysfunction characteristic of Alzheimer disease. PMID- 22318123 TI - Differential detection and distribution of microglial and hematogenous macrophage populations in the injured spinal cord of lys-EGFP-ki transgenic mice. AB - The acute inflammatory response that follows spinal cord injury (SCI) contributes to secondary injury that results in the expansion of the lesion and further loss of neurologic function. A cascade of receptor-mediated signaling events after SCI leads to activation of innate immune responses including the migration of microglia and active recruitment of circulating leukocytes. Because conventional techniques do not always distinguish macrophages derived from CNS-resident microglia from blood-derived monocytes, the role that each macrophage type performs cannot be assessed unambiguously in these processes. We demonstrate that, in the normal and spinal cord-injured lys-EGFP-ki transgenic mouse, enhanced green fluorescent protein (EGFP) is expressed only in mature hematopoietic granulomyelomonocytic cells and not in microglia. This allowed us to assess the temporal and spatial relationships between microglia-derived and hematogenous macrophages as well as neutrophils during a period of 6 weeks after clip compression SCI. Within the lesion, EGFP-positive monocyte-derived macrophages were found at the epicenter surrounded by EGFP-negative-activated microglia and microglia-derived macrophages. Neutrophils were not present when EGFP-positive monocyte-derived macrophages were depleted, indicating that neutrophil persistence in the lesion depended on the presence of these monocytes. Thus, these 2 distinct macrophage populations can be independently identified and tracked, thereby allowing their roles in acute and chronic stages of SCI associated inflammation to be defined. PMID- 22318124 TI - Unmyelinated axons show selective rostrocaudal pathology in the corpus callosum after traumatic brain injury. AB - Axonal injury is consistently observed after traumatic brain injury (TBI). Prior research has extensively characterized the post-TBI response in myelinated axons. Despite evidence that unmyelinated axons comprise a numerical majority of cerebral axons, pathologic changes in unmyelinated axons after TBI have not been systematically studied. To identify morphologic correlates of functional impairment of unmyelinated fibers after TBI, we assessed ultrastructural changes in corpus callosum axons. Adult rats received moderate fluid percussion TBI, which produced diffuse injury with no contusion. Cross-sectional areas of 13,797 unmyelinated and 3,278 intact myelinated axons were stereologically measured at survival intervals from 3 hours to 15 days after injury. The mean caliber of unmyelinated axons was significantly reduced at 3 to 7 days and recovered by 15 days, but the time course of this shrinkage varied among the genu, mid callosum, and splenium. Relatively large unmyelinated axons seemed to be particularly vulnerable. Injury-induced decreases in unmyelinated fiber density were also observed, but they were more variable than caliber reductions. By contrast, no significant morphometric changes were observed in myelinated axons. The finding of a preferential vulnerability in unmyelinated axons has implications for current concepts of axonal responses after TBI and for development of specifically targeted therapies. PMID- 22318125 TI - Intraneuronal immunoreactivity for the prion protein distinguishes a subset of E200K genetic from sporadic Creutzfeldt-Jakob Disease. AB - Recently, we reported widespread intraneuronal prion protein (PrP) immunoreactivity in genetic Creutzfeldt-Jakob disease (CJD) associated with the E200K mutation. Here, we evaluated 6 cases ofsporadic CJD MM type 1, 5 MV type 2, and 7 VV type 2 and compared their anatomical appearance with that of 29 E200K genetic CJD (gCJD) cases. We also performed double immunolabeling for ubiquitin, p62, early endosomal marker rab5, and immunogold electronmicroscopy in 3 cases. We identified 4 morphological types of intraneuronal PrP immunoreactivity: one type, defined as multiple globular structures, was significantly associated with a subset of E200K gCJD cases and was distinct from the intraneuronal small dotlike PrP immunoreactivity seen in sporadic CJD. Whereas the latter colocalized with rab5, there were single large (7.5 MUm-15 MUm) globular inclusion body-like structures detected predominantly but not exclusively in E200K gCJD; these were immunoreactive in part for ubiquitin and p62 and showed focal gamma-tubulin immunoreactivity, suggesting aggresome features. Ultrastructural examination using immunogold revealed PrP localization in aggresome-like structures and in autophagic vacuoles. These findings suggest that the permanent production of mutant PrP in the E200K gCJD cases overwhelms the ubiquitin-proteasome system and shifts the balance toward selectivemacroautophagy and/or to ubiquitinated inclusion body and aggresome formation as a cytoprotective effort to sequester the mutant protein. PMID- 22318126 TI - The earliest stage of cognitive impairment in transition from normal aging to Alzheimer disease is marked by prominent RNA oxidation in vulnerable neurons. AB - Although neuronal RNA oxidation is a prominent and established feature in age associated neurodegenerative disorders such as Alzheimer disease (AD), oxidative damage to neuronal RNA in aging and in the transitional stages from normal elderly to the onset of AD has not been fully examined. In this study, we used an in situ approachto identify an oxidized RNA nucleoside 8-hydroxyguanosine (8OHG) in the cerebral cortex of 65 individuals without dementia ranging in age from 0.3 to 86 years. We also examined brain samples from 20 elderly who were evaluated for their premortem clinicaldementia rating score and postmortem brain pathologic diagnoses to investigate preclinical AD and mild cognitive impairment. Relative density measurements of 8OHG-immunoreactivity revealed a statistically significant increase in neuronal RNA oxidation during aging in the hippocampus and the temporal neocortex. In subjects with mild cognitive impairment but not preclinical AD, neurons of the temporal cortex showed a higher burden of oxidized RNA compared to age-matched controls. These results indicate that, although neuronal RNA oxidation fundamentally occurs as an age-associated phenomenon, more prominent RNA damage than in normal aging correlates with the onset of cognitive impairment in the prodromal stage of AD. PMID- 22318127 TI - Expression and activation of EphA4 in the human brain after traumatic injury. AB - Glial scars that consist predominantly of reactive astrocytes create a major barrier to neuronal regeneration after traumatic brain injury (TBI). In experimental TBI, Eph receptors and their ephrin ligands are upregulated on reactive astrocytes at injury sites and inhibit axonal regeneration, but very little is known about Eph receptors in the human brain after TBI. A better understanding of the functions of glial cells and their interactions with inflammatory cells and injured axons will allow the development of treatment strategies that may promote regeneration. We analyzed EphA4 expression and activation in postmortem brain tissue from 19 patients who died after acute closed head injury and had evidence of diffuse axonal injury and 8 controls. We also examined downstream pathways that are mediated by EphA4 in human astrocyte cell cultures. Our results indicate that, after TBI in humans, EphA4 expression is upregulated and is associated with reactive astrocytes. The expression was increased shortly after the injury and remained activated for several days. EphA4 activation induced under inflammatory conditions in vitro was inhibited using unclustered EphA4 ligand. These results suggest that blocking EphA4 activation may represent a therapeutic approach for TBI and other types of brain injuries in humans. PMID- 22318128 TI - Microglial reaction in axonal crossroads is a hallmark of noncystic periventricular white matter injury in very preterm infants. AB - Disabilities after brain injury in very preterm infants have mainly been attributed to noncystic periventricular white matter injury (PWMI). We analyzed spatiotemporal patterns of PWMI in the brains of 18 very preterm infants (25-29 postconceptional weeks [pcw]), 7 preterm infants (30-34 pcw), and 10 preterm controls without PWMI. In very preterm infants, we examined PWMI in detail in 2 axonal crossroad areas in the frontal lobe: C1 (lateral to the lateral angle of the anterior horn of the lateral ventricle, at the exit of the internal capsule radiations) and C2 (above the corpus callosum and dorsal angle of the anterior horn). These brains had greater microglia-macrophage densities and activation but lesser astroglial reaction (glial fibrillary acidic protein and monocarboxylate transporter 1 expression) than in preterm cases with PWMI. In preterm infants, scattered necrotic foci were rimmed by axonal spheroids and ionized calcium binding adaptor molecule 1-positive macrophages. Diffuse lesions near these foci consisted primarily of hypertrophic and reactive astrocytes associated with fewer microglia. No differences in Olig2-positive preoligodendrocytes between noncystic PWMI and control cases were found. These data show that the growing axonal crossroad areas are highly vulnerable to PWMI in very preterm infants and highlight differences in glial activation patterns between very preterm and preterm infants. PMID- 22318129 TI - Is Roesleria subterranea a primary pathogen or a minor parasite of grapevines? Risk assessment and a diagnostic decision scheme. AB - In the past the root rot pathogen Roesleria subterranea (Ascomycota) was generally considered as a minor parasite, a view with which we were often confronted during field work in German wine-growing regions where this ascomycete recently caused serious problems in established vineyards and at replant sites. To irrevocably demonstrate that R. subterranea is not a minor, but a primary pathogen of grapevines (and fruit trees) a pest risk analysis was carried out according to the guidelines defined by EPPO standard series PM 5, which defines the information needed, and contains standardised, detailed key questions and a decision support scheme for risk analysis. Following the provided decision scheme, it becomes apparent that R. subterranea must be considered as a serious, primary pathogen for grapevines and fruit trees that can cause massive economic losses. Based on the literature, the pathogen seems to be ubiquitous in wine growing regions in cool climates of the northern hemisphere. It is likely that because of its growth below ground, the small fruiting bodies, and ambiguous symptoms above ground, R. subterranea has been overlooked in the past and therefore, has not been considered as primary pathogen for grapevine. Available published information together with experience from field trials was implemented into a diagnostic decision scheme which will, together with the comprehensive literature provided, be the basis (a) to implement quick and efficient diagnosis of this pathogen in the field and (b) to conduct risk analysis and management in areas where R. subterranea has not established yet. PMID- 22318130 TI - Suboptimal coronary blood flow after primary percutaneous coronary intervention for acute myocardial infarction: incidence, a simple risk score, and prognosis. AB - BACKGROUND: The aim of the present study is to investigate incidence, predictors, and long-term outcomes of suboptimal coronary flow after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) in a large population. METHODS: A total of 2056 consecutive patients with STEMI (mean age 56.2+/-11.7 years, 1738 men, 318 women) undergoing primary PCI were retrospectively enrolled in the present study. Patients were grouped as optimal [thrombolysis in myocardial infarction (TIMI) 3 flow, n=1939] and suboptimal (TIMI<=2 flow, n=117) according to the TIMI classification in the infarct-related artery at final coronary angiography after primary PCI, and were followed for in hospital and long-term outcomes for a mean period of 1.9+/-1.3 years (median of 22 months). RESULTS: Suboptimal coronary flow was observed in 5.7% (n=117) of the patients. Four variables, selected from the multivariate analysis, were weighted proportionally to their respective odds ratio for suboptimal coronary flow [predilatation before stenting (three points), Killip class 2/3 (two points), glomerular filtration rate<60 ml/min/1.73 m (two points), and anterior myocardial infarction (one point)]. Two strata of risk were defined (low risk, score 0-3; and high risk, score 4-8) and had a strong association with suboptimal coronary flow, and in-hospital and long-term cardiovascular mortalities. The suboptimal group had a higher prevalence of in-hospital mortality compared with the optimal group (22.2 vs. 1.2%, respectively, P<0.001). Long-term cardiovascular mortality was four-fold more in the suboptimal group than the optimal group (15.9 vs 3.7%, respectively, P<0.001). CONCLUSION: Suboptimal coronary flow after primary PCI in STEMI is strongly related with increased in-hospital and long-term cardiovascular mortalities. Predilatation before stenting is the most powerful predictor of suboptimal coronary flow. PMID- 22318131 TI - Postural instability and gait impairment during obstacle crossing in Parkinson's disease. AB - OBJECTIVE: To examine whether Parkinson's disease (PD) affects gait behavior and stability while walking over an obstacle. DESIGN: Parallel group comparisons were completed in which participants completed 5 trials of normal walking and 5 trials of obstacle crossing while gait kinematics and kinetics were collected. SETTING: University biomechanics laboratory. PARTICIPANTS: Individuals with PD (n=10) and age- and sex-matched healthy older adults (n=10). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Gait parameters, obstacle clearance parameters, and center of mass motion were calculated during normal walking and obstacle crossing. RESULTS: Results revealed that decrements in gait performance in individuals with PD were amplified during obstacle crossing, suggesting that due to disease related degradation, individuals with PD chose a more conservative strategy for obstacle crossing. Moreover, an increased duration of single limb support (18% increase), a decrease in anteroposterior range of motion (20% decrease), and an increase in mediolateral range of motion (36% increase, though not significant) coupled with the reduction in the distance between the center of pressure and center of mass (mean of 21% decrease across toe-off and heel strike) and increase in margin of stability (31% increase at toe-off and 71% increase at heel strike) may suggest that deficits in muscle strength and balance may contribute to this impairment. CONCLUSIONS: Persons with PD alter their behavior to reduce the mechanical demands and increase dynamic stability during obstacle avoidance tasks. PMID- 22318132 TI - Posterior reversible encephalopathy syndrome as a revealing manifestation of Guillain-Barre syndrome. AB - We report a patient with a Guillain-Barre syndrome (GBS) revealed by a posterior reversible encephalopathy syndrome (PRES). The PRES is typically associated with bilateral parieto-occipital T2 and FLAIR hyperintense MRI lesions and observed in various etiologic conditions leading to acute arterial hypertension. PRES results from a breakdown of the circulatory autoregulation, many in the posterior cerebral territories. GBS can be considered as an independent risk factor of PRES, due to acute dysautonomia and pain with consecutive arterial hypertension, as well as to cytokine production changing capillary permability. Such patients with PRES-revealed GBS may be treated with intravenous immunoglobulin therapy only after exclusion of any ischemic or hemorrhagic cerebral complications, and after control of the blood pressure and of the encephalopathic signs and symptoms. PMID- 22318133 TI - Plasmacytoid dendritic cells reduce HIV production in elite controllers. AB - HIV elite controllers (EC) are a rare group of HIV-infected patients who are able to maintain undetectable viral loads during a long period of time in the absence of antiretroviral treatment. Adaptive immunity and host genetic factors, although implicated, do not entirely explain this phenomenon. On the other hand, plasmacytoid dendritic cells (pDCs) are the principal type I interferon (IFN) producers in response to viral infection, and it is unknown whether pDCs are involved in the control of HIV infection in EC. In our study, we analyzed peripheral pDC levels and IFN-alpha production by peripheral blood mononuclear cells (PBMCs) in EC compared to other groups of HIV-infected patients, the ability of pDCs to reduce HIV production in vitro, and the mechanisms potentially involved. We showed preserved pDC counts and IFN-alpha production in EC. We also observed a higher capacity of pDCs from EC to reduce HIV production and to induce T cell apoptosis, whereas pDCs from viremic patients barely responded without previous Toll-like receptor 9 (TLR-9) stimulus. The preserved functionality of pDCs from EC to reduce viral production may be one of the mechanisms involved in the control of HIV viremia in these subjects. These results demonstrate the importance of innate immunity in HIV pathogenesis, and an understanding of pDC mechanisms would be helpful for the design of new therapies. PMID- 22318134 TI - Discovery of retroviral homologs in bats: implications for the origin of mammalian gammaretroviruses. AB - Gammaretroviruses infect a wide range of vertebrate species where they are associated with leukemias, neurological diseases and immunodeficiencies. However, the origin of these infectious agents is unknown. Through a phylogenetic analysis of viral gene sequences, we show that bats harbor an especially diverse set of gammaretroviruses. In particular, phylogenetic analysis places Rhinolophus ferrumequinum retrovirus (RfRV), a new gammaretrovirus identified by de novo analysis of the Rhinolophus ferrumequinum transcriptome, and six other gammaretroviruses from different bat species, as basal to other mammalian gammaretroviruses. An analysis of the similarity in the phylogenetic history between the gammaretroviruses and their bat hosts provided evidence for both host virus codivergence and cross-species transmission. Taken together, these data provide new insights into the origin of the mammalian gammaretroviruses. PMID- 22318135 TI - Superior induction of T cell responses to conserved HIV-1 regions by electroporated alphavirus replicon DNA compared to that with conventional plasmid DNA vaccine. AB - Vaccination using "naked" DNA is a highly attractive strategy for induction of pathogen-specific immune responses; however, it has been only weakly immunogenic in humans. Previously, we constructed DNA-launched Semliki Forest virus replicons (DREP), which stimulate pattern recognition receptors and induce augmented immune responses. Also, in vivo electroporation was shown to enhance immune responses induced by conventional DNA vaccines. Here, we combine these two approaches and show that in vivo electroporation increases CD8(+) T cell responses induced by DREP and consequently decreases the DNA dose required to induce a response. The vaccines used in this study encode the multiclade HIV-1 T cell immunogen HIVconsv, which is currently being evaluated in clinical trials. Using intradermal delivery followed by electroporation, the DREP.HIVconsv DNA dose could be reduced to as low as 3.2 ng to elicit frequencies of HIV-1-specific CD8(+) T cells comparable to those induced by 1 MUg of a conventional pTH.HIVconsv DNA vaccine, representing a 625-fold molar reduction in dose. Responses induced by both DREP.HIVconsv and pTH.HIVconsv were further increased by heterologous vaccine boosts employing modified vaccinia virus Ankara MVA.HIVconsv and attenuated chimpanzee adenovirus ChAdV63.HIVconsv. Using the same HIVconsv vaccines, the mouse observations were supported by an at least 20 fold-lower dose of DNA vaccine in rhesus macaques. These data point toward a strategy for overcoming the low immunogenicity of DNA vaccines in humans and strongly support further development of the DREP vaccine platform for clinical evaluation. PMID- 22318136 TI - The human respiratory syncytial virus matrix protein is required for maturation of viral filaments. AB - An experimental system was developed to generate infectious human respiratory syncytial virus (HRSV) lacking matrix (M) protein expression (M-null virus) from cDNA. The role of the M protein in virus assembly was then examined by infecting HEp-2 and Vero cells with the M-null virus and assessing the impact on infectious virus production and viral protein trafficking. In the absence of M, the production of infectious progeny was strongly impaired. Immunofluorescence (IF) microscopy analysis using antibodies against the nucleoprotein (N), attachment protein (G), and fusion protein (F) failed to detect the characteristic virus induced cell surface filaments, which are believed to represent infectious virions. In addition, a large proportion of the N protein was detected in viral replication factories termed inclusion bodies (IBs). High-resolution analysis of the surface of M-null virus-infected cells by field emission scanning electron microscopy (SEM) revealed the presence of large areas with densely packed, uniformly short filaments. Although unusually short, these filaments were otherwise similar to those induced by an M-containing control virus, including the presence of the viral G and F proteins. The abundance of the short, stunted filaments in the absence of M indicates that M is not required for the initial stages of filament formation but plays an important role in the maturation or elongation of these structures. In addition, the absence of mature viral filaments and the simultaneous increase in the level of the N protein within IBs suggest that the M protein is involved in the transport of viral ribonucleoprotein (RNP) complexes from cytoplasmic IBs to sites of budding. PMID- 22318137 TI - Immunodominant "asymptomatic" herpes simplex virus 1 and 2 protein antigens identified by probing whole-ORFome microarrays with serum antibodies from seropositive asymptomatic versus symptomatic individuals. AB - Herpes simplex virus 1 (HSV-1) and HSV-2 are medically significant pathogens. The development of an effective HSV vaccine remains a global public health priority. HSV-1 and HSV-2 immunodominant "asymptomatic" antigens (ID-A-Ags), which are strongly recognized by B and T cells from seropositive healthy asymptomatic individuals, may be critical to be included in an effective immunotherapeutic HSV vaccine. In contrast, immunodominant "symptomatic" antigens (ID-S-Ags) may exacerbate herpetic disease and therefore must be excluded from any HSV vaccine. In the present study, proteome microarrays of 88 HSV-1 and 84 HSV-2 open reading frames(ORFs) (ORFomes) were constructed and probed with sera from 32 HSV-1-, 6 HSV-2-, and 5 HSV-1/HSV-2-seropositive individuals and 47 seronegative healthy individuals (negative controls). The proteins detected in both HSV-1 and HSV-2 proteome microarrays were further classified according to their recognition by sera from HSV-seropositive clinically defined symptomatic (n = 10) and asymptomatic (n = 10) individuals. We found that (i) serum antibodies recognized an average of 6 ORFs per seropositive individual; (ii) the antibody responses to HSV antigens were diverse among HSV-1- and HSV-2-seropositive individuals; (iii) panels of 21 and 30 immunodominant antigens (ID-Ags) were identified from the HSV 1 and HSV-2 ORFomes, respectively, as being highly and frequently recognized by serum antibodies from seropositive individuals; and (iv) interestingly, four HSV 1 and HSV-2 cross-reactive asymptomatic ID-A-Ags, US4, US11, UL30, and UL42, were strongly and frequently recognized by sera from 10 of 10 asymptomatic patients but not by sera from 10 of 10 symptomatic patients (P < 0.001). In contrast, sera from symptomatic patients preferentially recognized the US10 ID-S-Ag (P < 0.001). We have identified previously unreported immunodominant HSV antigens, among which were 4 ID-A-Ags and 1 ID-S-Ag. These newly identified ID-A-Ags could lead to the development of an efficient "asymptomatic" vaccine against ocular, orofacial, and genital herpes. PMID- 22318138 TI - Mucosal simian immunodeficiency virus transmission in African green monkeys: susceptibility to infection is proportional to target cell availability at mucosal sites. AB - African green monkeys (AGMs) are naturally infected with a simian immunodeficiency virus (SIVagm) that is nonpathogenic in its host. Although SIVagm is common and widespread, little is known about the mechanisms that govern its transmission. Since the earliest virus-host interactions may provide key insights into the nonpathogenic phenotype of SIVagm, we developed a mucosal transmission model for this virus. Using plasma from an acutely infected AGM as the virus inoculum, we exposed adult and juvenile AGMs, as well as pigtailed macaques (PTMs) as a nonnatural host control, by mucosal routes to increasing titers of virus and compared the doses needed to establish a productive infection. Four juvenile and four adult AGMs as well as two PTMs were intrarectally (IR) exposed, while two additional adult female AGMs were intravaginally (IVAG) exposed. No animal became infected following exposure to 10(5) RNA copies. Both PTMs but none of the AGMs became infected following exposure to 10(6) RNA copies. Finally, all adult AGMs and two of the four juvenile AGMs became infected following exposure to 10(7) RNA copies, acquiring either one (2 IR infected juveniles, 1 IR infected adult, 2 IVAG infected adults) or two (3 IR infected adults) transmitted founder viruses. These results were consistent with immunophenotypic data, which revealed a significant correlation between the percentage of CD4(+) T cells expressing CCR5 in the mucosa and the susceptibility to infection, in terms of both the viral dose and the numbers of transmitted founder viruses. Moreover, studies of uninfected AGMs showed that the fraction of CCR5-expressing CD4(+) T cells increased significantly with age. These results indicate that (i) AGMs are readily infected with SIVagm by both intrarectal and intravaginal routes, (ii) susceptibility to infection is proportional to the number of available CCR5(+) CD4(+) target cells in the mucosa, and (iii) the paucity of CCR5(+) CD4(+) target cells in infant and juvenile AGMs may explain the near absence of vertical transmission. PMID- 22318139 TI - PB1-F2 modulates early host responses but does not affect the pathogenesis of H1N1 seasonal influenza virus. AB - In the context of infections with highly pathogenic influenza A viruses, the PB1 F2 protein contributes to virulence and enhances lung inflammation. In contrast, its role in the pathogenesis of seasonal influenza viral strains is less clear, especially in the H1N1 subtype, where strains can have a full-length 87- to 90 amino-acid protein, a truncated 57-amino-acid version, or lack the protein altogether. Toward this, we introduced the full-length 1918 PB1-F2, or prevented PB1-F2 expression, in H1N1 A/USSR/90/77, a seasonal strain that naturally expresses a truncated PB1-F2. All viruses replicated with similar efficiency in ferret or macaque ex vivo lung cultures and elicited similar cytokine mRNA profiles. In contrast, the virus expressing the 1918 PB1-F2 protein caused a delay of proinflammatory responses in ferret blood-derived macrophages, while the PB1-F2 knockout virus resulted in a more rapid response. A similar but less pronounced delay in innate immune activation was also observed in the nasal wash cells of ferrets infected with the 1918 PB1-F2-expressing virus. However, the three viruses did not differ in their virulence or clinical course in ferrets, supporting speculations that PB1-F2 is of limited importance for the pathogenesis of primary viral infection with human seasonal H1N1 viruses. PMID- 22318140 TI - The majority of freshly sorted simian immunodeficiency virus (SIV)-specific CD8(+) T cells cannot suppress viral replication in SIV-infected macrophages. AB - Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) primarily infect activated CD4(+) T cells but can infect macrophages. Surprisingly, ex vivo tetramer-sorted SIV-specific CD8(+) T cells that eliminated and suppressed viral replication in SIV-infected CD4(+) T cells failed to do so in SIV-infected macrophages. It is possible, therefore, that while AIDS virus infected macrophages constitute only a small percentage of all virus-infected cells, they may be relatively resistant to CD8(+) T cell-mediated lysis and continue to produce virus over long periods of time. PMID- 22318141 TI - Restoration of TLR3-activated myeloid dendritic cell activity leads to improved natural killer cell function in chronic hepatitis B virus infection. AB - There is increasing evidence that the function of NK cells in patients with chronic hepatitis B (CHB) infection is impaired. The underlying mechanism for the impaired NK cell function is still unknown. Since myeloid dendritic cells (mDC) are potent inducers of NK cells, we investigated the functional interaction of mDC and NK cells in CHB and the influence of antiviral therapy. Blood BDCA1(+) mDC and NK cells were isolated from 16 healthy controls or 39 CHB patients at baseline and during 6 months of antiviral therapy. After activation of mDC with poly(I . C) and gamma interferon (IFN-gamma), mDC were cocultured with NK cells. Phenotype and function were analyzed in detail by flow cytometry and enzyme linked immunosorbent assay. Our findings demonstrate that on poly(I . C)/IFN gamma-stimulated mDC from CHB patients, the expression of costimulatory molecules was enhanced, while cytokine production was reduced. In cocultures of poly(I . C)/IFN-gamma-stimulated mDC and NK cells obtained from CHB patients, reduced mDC induced NK cell activation (i.e., CD69 expression) and IFN-gamma production compared to those in healthy individuals was observed. Antiviral therapy normalized mDC activity, since decreased expression of CD80 and CD86 on DC and of HLA-E on NK cells was observed, while poly(I . C)/IFN-gamma-induced cytokine production by mDC was enhanced. In parallel, successful antiviral therapy resulted in improved mDC-induced NK cell activation and IFN-gamma production. These data demonstrate that CHB patients display a diminished functional interaction between poly(I . C)/IFN-gamma activated mDC and NK cells due to impaired mDC function, which can be partially restored by antiviral therapy. Enhancing this reciprocal interaction could reinforce the innate and thus the adaptive T cell response, and this may be an important step in achieving effective antiviral immunity. PMID- 22318142 TI - Nonstructural proteins 7 and 8 of feline coronavirus form a 2:1 heterotrimer that exhibits primer-independent RNA polymerase activity. AB - Nonstructural proteins 7 and 8 of severe acute respiratory syndrome coronavirus (SARS-CoV) have previously been shown by X-ray crystallography to form an 8:8 hexadecamer. In addition, it has been demonstrated that N-terminally His(6) tagged SARS-CoV Nsp8 is a primase able to synthesize RNA oligonucleotides with a length of up to 6 nucleotides. We present here the 2.6-A crystal structure of the feline coronavirus (FCoV) Nsp7:Nsp8 complex, which is a 2:1 heterotrimer containing two copies of the alpha-helical Nsp7 with conformational differences between them, and one copy of Nsp8 that consists of an alpha/beta domain and a long-alpha-helix domain. The same stoichiometry is found for the Nsp7:Nsp8 complex in solution, as demonstrated by chemical cross-linking, size exclusion chromatography, and small-angle X-ray scattering. Furthermore, we show that FCoV Nsp8, like its SARS-CoV counterpart, is able to synthesize short oligoribonucleotides of up to 6 nucleotides in length when carrying an N-terminal His(6) tag. Remarkably, the same protein harboring the sequence GPLG instead of the His(6) tag at its N terminus exhibits a substantially increased, primer independent RNA polymerase activity. Upon addition of Nsp7, the RNA polymerase activity is further enhanced so that RNA up to template length (67 nucleotides) can be synthesized. Further, we show that the unprocessed intermediate polyprotein Nsp7-10 of human coronavirus (HCoV) 229E is also capable of synthesizing oligoribonucleotides up to a chain length of six. These results indicate that in case of FCoV as well as of HCoV 229E, the formation of a hexadecameric Nsp7:Nsp8 complex is not necessary for RNA polymerase activity. Further, the FCoV Nsp7:Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length. PMID- 22318143 TI - The histone deacetylase inhibitor valproic acid lessens NK cell action against oncolytic virus-infected glioblastoma cells by inhibition of STAT5/T-BET signaling and generation of gamma interferon. AB - Tumor virotherapy has been and continues to be used in clinical trials. One barrier to effective viral oncolysis, consisting of the interferon (IFN) response induced by viral infection, is inhibited by valproic acid (VPA) and other histone deacetylase inhibitors (HDACi). Innate immune cell recruitment and activation have been shown to be deleterious to the efficacy of oncolytic herpes simplex virus (oHSV) infection, and in this report we demonstrate that VPA limits this deleterious response. VPA, administered prior to oHSV inoculation in an orthotopic glioblastoma mouse model, resulted in a decline in NK and macrophage recruitment into tumor-bearing brains at 6 and 24 h post-oHSV infection. Interestingly, there was a robust rebound of recruitment of these cells at 72 h post-oHSV infection. The observed initial decline in immune cell recruitment was accompanied by a reduction in their activation status. VPA was also found to have a profound immunosuppressive effect on human NK cells in vitro. NK cytotoxicity was abrogated following exposure to VPA, consistent with downmodulation of cytotoxic gene expression of granzyme B and perforin at the mRNA and protein levels. In addition, suppression of gamma IFN (IFN-gamma) production by VPA was associated with decreased STAT5 phosphorylation and dampened T-BET expression. Despite VPA-mediated immune suppression, mice were not at significantly increased risk for HSV encephalitis. These findings indicate that one of the avenues by which VPA enhances oHSV efficacy is through initial suppression of immune cell recruitment and inhibition of inflammatory cell pathways within NK cells. PMID- 22318144 TI - Enhanced susceptibility of Ago1/3 double-null mice to influenza A virus infection. AB - RNA interference (RNAi) is a critical component of many cellular antiviral responses in plants, invertebrates, and mammals. However, its in vivo role in host protection from the negative-sense RNA virus influenza virus type A (flu) is unclear. Here we have examined the role of RNAi in host defense to flu by analyzing Argonaute 1 and 3 double-knockout mice deficient in components of the RNA-induced silencing complex. Compared to littermate controls, flu-infected double-knockout mice exhibited increased mortality, consistent with more severe alveolitis and pneumonitis. These data indicate that optimal resistance to flu requires Argonaute 1 and/or 3. Enhanced mortality of double-knockout mice was not associated either with increased viral replication or with differential pulmonary recruitment or function of innate and adaptive immune cells. Given the absence of detectable immune defects, our results support the notion that the enhanced flu susceptibility of double-knockout mice arises from an intrinsic impairment in the ability of lung cells to tolerate flu-elicited inflammation. PMID- 22318145 TI - Tiled microarray identification of novel viral transcript structures and distinct transcriptional profiles during two modes of productive murine gammaherpesvirus 68 infection. AB - We applied a custom tiled microarray to examine murine gammaherpesvirus 68 (MHV68) polyadenylated transcript expression in a time course of de novo infection of fibroblast cells and following phorbol ester-mediated reactivation from a latently infected B cell line. During de novo infection, all open reading frames (ORFs) were transcribed and clustered into four major temporal groups that were overlapping yet distinct from clusters based on the phorbol ester-stimulated B cell reactivation time course. High-density transcript analysis at 2-h intervals during de novo infection mapped gene boundaries with a 20-nucleotide resolution, including a previously undefined ORF73 transcript and the MHV68 ORF63 homolog of Kaposi's sarcoma-associated herpesvirus vNLRP1. ORF6 transcript initiation was mapped by tiled array and confirmed by 5' rapid amplification of cDNA ends. The ~1.3-kb region upstream of ORF6 was responsive to lytic infection and MHV68 RTA, identifying a novel RTA-responsive promoter. Transcription in intergenic regions consistent with the previously defined expressed genomic regions was detected during both types of productive infection. We conclude that the MHV68 transcriptome is dynamic and distinct during de novo fibroblast infection and upon phorbol ester-stimulated B cell reactivation, highlighting the need to evaluate further transcript structure and the context-dependent molecular events that govern viral gene expression during chronic infection. PMID- 22318146 TI - Hepatitis C virus induces CD81 and claudin-1 endocytosis. AB - Hepatitis C virus (HCV) leads to progressive liver disease and hepatocellular carcinoma. Current treatments are only partially effective, and new therapies targeting viral and host pathways are required. Virus entry into a host cell provides a conserved target for therapeutic intervention. Tetraspanin CD81, scavenger receptor class B member I, and the tight-junction proteins claudin-1 and occludin have been identified as essential entry receptors. Limited information is available on the role of receptor trafficking in HCV entry. We demonstrate here that anti-CD81 antibodies inhibit HCV infection at late times after virus internalization, suggesting a role for intracellular CD81 in HCV infection. Several tetraspanins have been reported to internalize via motifs in their C-terminal cytoplasmic domains; however, CD81 lacks such motifs, leading several laboratories to suggest a limited role for CD81 endocytosis in HCV entry. We demonstrate CD81 internalization via a clathrin- and dynamin-dependent process, independent of its cytoplasmic domain, suggesting a role for associated partner proteins in regulating CD81 trafficking. Live cell imaging demonstrates CD81 and claudin-1 coendocytosis and fusion with Rab5 expressing endosomes, supporting a role for this receptor complex in HCV internalization. Receptor specific antibodies and HCV particles increase CD81 and claudin-1 endocytosis, supporting a model wherein HCV stimulates receptor trafficking to promote particle internalization. PMID- 22318147 TI - Live attenuated herpes simplex virus 2 glycoprotein E deletion mutant as a vaccine candidate defective in neuronal spread. AB - A herpes simplex virus 2 (HSV-2) glycoprotein E deletion mutant (gE2-del virus) was evaluated as a replication-competent, attenuated live virus vaccine candidate. The gE2-del virus is defective in epithelial cell-to-axon spread and in anterograde transport from the neuron cell body to the axon terminus. In BALB/c and SCID mice, the gE2-del virus caused no death or disease after vaginal, intravascular, or intramuscular inoculation and was 5 orders of magnitude less virulent than wild-type virus when inoculated directly into the brain. No infectious gE2-del virus was recovered from dorsal root ganglia (DRG) after multiple routes of inoculation; however, gE2-del DNA was detected by PCR in lumbosacral DRG at a low copy number in some mice. Importantly, no recurrent vaginal shedding of gE2-del DNA was detected in immunized guinea pigs. Intramuscular immunization outperformed subcutaneous immunization in all parameters evaluated, although individual differences were not significant, and two intramuscular immunizations were more protective than one. Immunized animals had reduced vaginal disease, vaginal titers, DRG infection, recurrent genital lesions, and recurrent vaginal shedding of HSV-2 DNA; however, protection was incomplete. A combined modality immunization using live virus and HSV-2 glycoprotein C and D subunit antigens in guinea pigs did not totally eliminate recurrent lesions or recurrent vaginal shedding of HSV-2 DNA. The gE2-del virus used as an immunotherapeutic vaccine in previously HSV-2-infected guinea pigs greatly reduced the frequency of recurrent genital lesions. Therefore, the gE2 del virus is safe, other than when injected at high titer into the brain, and is efficacious as a prophylactic and immunotherapeutic vaccine. PMID- 22318148 TI - RNA synthesis by the brome mosaic virus RNA-dependent RNA polymerase in human cells reveals requirements for de novo initiation and protein-protein interaction. AB - Brome mosaic virus (BMV) is a model positive-strand RNA virus whose replication has been studied in a number of surrogate hosts. In transiently transfected human cells, the BMV polymerase 2a activated signaling by the innate immune receptor RIG-I, which recognizes de novo-initiated non-self-RNAs. Active-site mutations in 2a abolished RIG-I activation, and coexpression of the BMV 1a protein stimulated 2a activity. Mutations previously shown to abolish 1a and 2a interaction prevented the 1a-dependent enhancement of 2a activity. New insights into 1a-2a interaction include the findings that helicase active site of 1a is required to enhance 2a polymerase activity and that negatively charged amino acid residues between positions 110 and 120 of 2a contribute to interaction with the 1a helicase-like domain but not to the intrinsic polymerase activity. Confocal fluorescence microscopy revealed that the BMV 1a and 2a colocalized to perinuclear region in human cells. However, no perinuclear spherule-like structures were detected in human cells by immunoelectron microscopy. Sequencing of the RNAs coimmunoprecipitated with RIG-I revealed that the 2a-synthesized short RNAs are derived from the message used to translate 2a. That is, 2a exhibits a strong cis preference for BMV RNA2. Strikingly, the 2a RNA products had initiation sequences (5'-GUAAA-3') identical to those from the 5' sequence of the BMV genomic RNA2 and RNA3. These results show that the BMV 2a polymerase does not require other BMV proteins to initiate RNA synthesis but that the 1a helicase domain, and likely helicase activity, can affect RNA synthesis by 2a. PMID- 22318149 TI - Functional hierarchy of herpes simplex virus 1 viral glycoproteins in cytoplasmic virion envelopment and egress. AB - Herpes simplex virus 1 (HSV-1) viral glycoproteins gD (carboxyl terminus), gE, gK, and gM, the membrane protein UL20, and membrane-associated protein UL11 play important roles in cytoplasmic virion envelopment and egress from infected cells. We showed previously that a recombinant virus carrying a deletion of the carboxyl terminal 29 amino acids of gD (gDDeltact) and the entire gE gene (DeltagE) did not exhibit substantial defects in cytoplasmic virion envelopment and egress (H. C. Lee et al., J. Virol. 83:6115-6124, 2009). The recombinant virus DeltagM2, engineered not to express gM, produced a 3- to 4-fold decrease in viral titers and a 50% reduction in average plaque sizes in comparison to the HSV-1(F) parental virus. The recombinant virus containing all three mutations, gDDeltact DeltagM2-DeltagE, replicated approximately 1 log unit less efficiently than the HSV-1(F) parental virus and produced viral plaques which were on average one third the size of those of HSV-1(F). The recombinant virus DeltaUL11-DeltagM2, engineered not to express either UL11 or gM, replicated more than 1 log unit less efficiently and produced significantly smaller plaques than UL11-null or gM-null viruses alone, in agreement with the results of Leege et al. (T. Leege et al., J. Virol. 83:896-907, 2009). Analyses of particle-to-PFU ratios, relative plaque size, and kinetics of virus growth and ultrastructural visualization of glycoprotein-deficient mutant and wild-type virions indicate that gDDeltact, gE, and gM function in a cooperative but not redundant manner in infectious virion morphogenesis. Overall, comparisons of single, double, and triple mutant viruses generated in the same HSV-1(F) genetic background indicated that lack of either UL20 or gK expression caused the most severe defects in cytoplasmic envelopment, egress, and infectious virus production, followed by the double deletion of UL11 and gM. PMID- 22318150 TI - Prasinoviruses of the marine green alga Ostreococcus tauri are mainly species specific. AB - Prasinoviruses infecting unicellular green algae in the order Mamiellales (class Mamiellophyceae) are commonly found in coastal marine waters where their host species frequently abound. We tested 40 Ostreococcus tauri viruses on 13 independently isolated wild-type O. tauri strains, 4 wild-type O. lucimarinus strains, 1 Ostreococcus sp. ("Ostreococcus mediterraneus") clade D strain, and 1 representative species of each of two other related species of Mamiellales, Bathycoccus prasinos and Micromonas pusilla. Thirty-four out of 40 viruses infected only O. tauri, 5 could infect one other species of the Ostreococcus genus, and 1 infected two other Ostreococcus spp., but none of them infected the other genera. We observed that the overall susceptibility pattern of Ostreococcus strains to viruses was related to the size of two host chromosomes known to show intraspecific size variations, that genetically related viruses tended to infect the same host strains, and that viruses carrying inteins were strictly strain specific. Comparison of two complete O. tauri virus proteomes revealed at least three predicted proteins to be candidate viral specificity determinants. PMID- 22318151 TI - CRM1-dependent trafficking of retroviral Gag proteins revisited. AB - We analyzed the nuclear trafficking ability of Gag proteins from six retroviral genera. Contrary to a previous report, human immunodeficiency virus type 1 (HIV 1) Gag showed no propensity to cycle through the nucleus. The only Gag protein that displayed CRM1-dependent nuclear cycling was that of Rous sarcoma virus (RSV). Surprisingly, this cycling could be eliminated without compromising infectivity by replacing the RSV Gag N-terminal matrix (MA) domain with HIV MA. PMID- 22318152 TI - Nuclear export and expression of human T-cell leukemia virus type 1 tax/rex mRNA are RxRE/Rex dependent. AB - Human T-cell leukemia virus type 1 (HTLV-1) is a complex retrovirus associated with the lymphoproliferative disease adult T-cell leukemia/lymphoma (ATL) and the neurodegenerative disorder tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). Replication of HTLV-1 is under the control of two major trans-acting proteins, Tax and Rex. Previous studies suggested that Tax activates transcription from the viral long terminal repeat (LTR) through recruitment of cellular CREB and transcriptional coactivators. Other studies reported that Rex acts posttranscriptionally and allows the cytoplasmic export of unspliced or incompletely spliced viral mRNAs carrying gag/pol and env only. As opposed to HIV's Rev-responsive element (RRE), the Rex-responsive element (RxRE) is present in all viral mRNAs in HTLV-1. However, based on indirect observations, it is believed that nuclear export and expression of the doubly spliced tax/rex RNA are Rex independent. In this study, we demonstrate that Rex does stimulate Tax expression, through nuclear-cytoplasmic export of the tax/rex RNA, even though a Rex-independent basal export mechanism exists. This effect was dependent upon the RxRE element and the RNA-binding activity of Rex. In addition, Rex-mediated export of tax/rex RNA was CRM1 dependent and inhibited by leptomycin B treatment. RNA immunoprecipitation (RNA-IP) experiments confirmed Rex binding to the tax/rex RNA in both transfected cells with HTLV-1 molecular clones and HTLV-1-infected T cells. Since both Rex and p30 interact with the tax/rex RNA and with one another, this may offer a temporal and dynamic regulation of HTLV-1 replication. Our results shed light on HTLV-1 replication and reveal a more complex regulatory network than previously anticipated. PMID- 22318153 TI - The latent membrane protein 1 (LMP1) oncogene of Epstein-Barr virus can simultaneously induce and inhibit apoptosis in B cells. AB - The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) regulates its own expression and the expression of human genes via its two functional moieties; the transmembrane domains of LMP1 are required to regulate its expression via the unfolded protein response (UPR) and autophagy in B cells, and the carboxy terminal domain of LMP1 activates cellular signaling pathways that affect cellular proliferation and survival. An apparent anomaly in the complex regulation of the UPR and autophagy by LMP1 is that the induction of either pathway can lead to cellular death, yet neither EBV-infected B cells nor B cells expressing only LMP1 die. Thus, we sought to understand how B cells that express LMP1 survive. The transmembrane domains of LMP1 activated apoptosis in B cells, the apoptosis required the UPR, and the carboxy-terminal domain of LMP1 blocked this apoptosis. The expression of the mRNA of Bcl2a1, encoding an antiapoptotic homolog of BCL2, correlated directly with the expression of LMP1 in EBV-positive B-cell strains, and its expression inhibited the apoptosis induced by the transmembrane domains of LMP1. These findings illustrate how the carboxy-terminal domain of LMP1 supports survival of B cells in the presence of the deleterious effects of the complex regulation of this viral oncogene. PMID- 22318154 TI - Discovery of potential diagnostic and vaccine antigens in herpes simplex virus 1 and 2 by proteome-wide antibody profiling. AB - Routine serodiagnosis of herpes simplex virus (HSV) infections is currently performed using recombinant glycoprotein G (gG) antigens from herpes simplex virus 1 (HSV-1) and HSV-2. This is a single-antigen test and has only one diagnostic application. Relatively little is known about HSV antigenicity at the proteome-wide level, and the full potential of mining the antibody repertoire to identify antigens with other useful diagnostic properties and candidate vaccine antigens is yet to be realized. To this end we produced HSV-1 and -2 proteome microarrays in Escherichia coli and probed them against a panel of sera from patients serotyped using commercial gG-1 and gG-2 (gGs for HSV-1 and -2, respectively) enzyme-linked immunosorbent assays. We identified many reactive antigens in both HSV-1 and -2, some of which were type specific (i.e., recognized by HSV-1- or HSV-2-positive donors only) and others of which were nonspecific or cross-reactive (i.e., recognized by both HSV-1- and HSV-2-positive donors). Both membrane and nonmembrane virion proteins were antigenic, although type-specific antigens were enriched for membrane proteins, despite being expressed in E. coli. PMID- 22318155 TI - Decreased anandamide transporter activity and calcitonin gene-related peptide production in spontaneously hypertensive rats: role of angiotensin II. AB - In the present study, we investigated the role of angiotensin II in regulating the anandamide transporter activity and resultant calcitonin gene-related peptide (CGRP) production in spontaneously hypertensive rats (SHRs). Systolic blood pressure, plasma levels of anandamide, angiotensin II and CGRP, CGRP mRNA expression in dorsal root ganglion and anandamide transporter activity in peripheral blood lymphocytes were measured in SHRs treated with selective angiotensin II type 1 receptor antagonist losartan. Rat peripheral blood lymphocytes were isolated to examine the effect of exogenous angiotensin II on anandamide-induced CGRP mRNA expression, anandamide transporter activity and intracellular reactive oxygen species production in presence or absence of losartan and antioxidant n-acetyl-cysteine. In SHRs, the plasma level of angiotensin II and anandamide was elevated, but the anandamide transporter activity was attenuated concomitantly with decreased CGRP production. Treatment with losartan for 2weeks produced depressor effect, restored the reduced anandamide transporter activity, decreased the plasma anandamide level and increased the plasma level and mRNA expression of CGRP in SHRs. In cultured lymphocytes, up-regulation of CGRP mRNA expression by exogenous administration of anandamide was inhibited by anandamide transporter blocker and angiotensin II. Angiotensin II also inhibited the anandamide transporter activity concentration dependently while increased intracellular reactive oxygen species production, which was reversed by pretreatment with losartan or n-acetyl-cysteine. The present findings suggest that angiotensin II plays a critical role in mediating the decrease in anandamide transporter activity and CGRP production in SHRs, which is likely due to activation angiotensin II type 1 receptor and resultant reactive oxygen species production. PMID- 22318156 TI - Discovery and hit-to-lead optimization of pyrrolopyrimidines as potent, state dependent Na(v)1.7 antagonists. AB - Herein we describe the discovery, optimization, and structure-activity relationships of novel potent pyrrolopyrimidine Na(v)1.7 antagonists. Hit-to-lead SAR studies of the pyrrolopyrimidine core, head, and tail groups of the molecule led to the identification of pyrrolopyrimidine 48 as exceptionally potent Na(v)1.7 blocker with good selectivity over hERG and improved microsomal stability relative to our hit molecule and pyrazolopyrimidine 8 as a promising starting point for future optimization efforts. PMID- 22318157 TI - Design, synthesis, single-crystal and preliminary antitumor activity of novel arenesulfonylimidazolidin-2-ones. AB - Novel series of 1-(arenesulfonyl)imidazolidin-2-one (3a-i) and 1,3 bis(arenesulfonyl)imidazolidin-2-one (5a-i) have been synthesized and tested for their antitumor activity against 60 tumor cell lines taken from nine different organs. A significant inhibition for cancer cells was observed with series 5a-i compounds compared with the series 3a-i which showed a weak inhibition. Compounds 5a-i showed good inhibitory effect at the lung cancer HOP-92 and renal cancer CAKI-1 and UO-31 cell lines. Compound 5e showed remarkable broad-spectrum antitumor activity. PMID- 22318158 TI - Synthesis and evaluation of cytotoxic effects of novel alpha-methylenelactone tetracyclic diterpenoids. AB - A series of tetracyclic diterpenoids bearing the alpha-methylenelactone group have been synthesized and screened for their in vitro anti-tumor activities against six human cancer cell lines. The results showed that compounds 1c, 2a and 2b exhibited significant cytotoxicity superior to the positive control doxorubicin hydrochloride against MDA-MB-231, K562 and HepG2 cell lines. In particular, compound 2b was identified as the most promising anticancer agent against HepG2 cells with IC(50) value of 0.09MUM. PMID- 22318159 TI - 3,5-Disubstituted indole derivatives as selective human neuronal nitric oxide synthase (nNOS) inhibitors. AB - A series of 3,5-disubstituted indole derivatives was designed, synthesized and evaluated as inhibitors of human nitric oxide synthase (NOS). Various guanidine isosteric groups were explored at the 5-position of the indole ring, while keeping the basic amine side chain such as N-methylpiperidine ring, fixed at the 3-position of the indole ring. Compounds having 2-thiophene amidine and 2-furanyl amidine groups (7, 8, 10 and 12) showed increased activity for human neuronal NOS and good selectivity over endothelial and inducible NOS isoforms. Compound 8 was shown to reverse (10mg/kg, ip) thermal hyperalgesia in the L(5)/L(6) spinal nerve ligation (neuropathic pain) model and was devoid of any significant drug-drug interaction potential due to cytochrome P450 inhibition or cardiovascular liabilities associated with the inhibition of endothelial NOS. PMID- 22318160 TI - Radiosynthesis of PET radiotracer as a prodrug for imaging group II metabotropic glutamate receptors in vivo. AB - Group II metabotropic glutamate receptors (mGluRs) have been implicated in a variety of neurological and psychiatric disorders in recent studies. As a noninvasive medical imaging technique and a powerful tool in neurological research, positron emission tomography (PET) offers the possibility to visualize and study group II mGluRs in vivo under physiologic and pathologic conditions. We synthesized a PET tracer, (S,S,S)-2-(2-carboxycyclopropyl)-2-(3 [(11)C]methoxyphenethyl) glycine dimethyl ester ([(11)C]CMGDE), as a prodrug for group II mGluRs, and studied its preliminary biological properties in Sprague Dawley rats to visualize group II mGluRs. The microPET studies demonstrated that [(11)C]CMGDE readily penetrated into the brain and the radiotracer generated from [(11)C]CMGDE had fast reversible binding in the group II mGluRs rich regions including striatum, hippocampus and different cortical areas. Blocking studies with LY341495 showed 20-30% decrease of binding of the radiotracer generated from [(11)C]CMGDE in all brain areas with the highest decrease in the striatum 31.5+/ 3.2%. The results show [(11)C]CMGDE is the first PET tracer that is brain penetrating and can be used to image group II mGluRs in vivo. PMID- 22318162 TI - Determining the optimal newborn screening protocol for cystic fibrosis. PMID- 22318161 TI - Significance of the microbiome in obstructive lung disease. AB - The composition of the lung microbiome contributes to both health and disease, including obstructive lung disease. Because it has been estimated that over 70% of the bacterial species on body surfaces cannot be cultured by currently available techniques, traditional culture techniques are no longer the gold standard for microbial investigation. Advanced techniques that identify bacterial sequences, including the 16S ribosomal RNA gene, have provided new insights into the depth and breadth of microbiota present both in the diseased and normal lung. In asthma, the composition of the microbiome of the lung and gut during early childhood development may play a key role in the development of asthma, while specific airway microbiota are associated with chronic asthma in adults. Early bacterial stimulation appears to reduce asthma susceptibility by helping the immune system develop lifelong tolerance to innocuous antigens. By contrast, perturbations in the microbiome from antibiotic use may increase the risk for asthma development. In chronic obstructive pulmonary disease, bacterial colonisation has been associated with a chronic bronchitic phenotype, increased risk of exacerbations, and accelerated loss of lung function. In cystic fibrosis, studies utilising culture-independent methods have identified associations between decreased bacterial community diversity and reduced lung function; colonisation with Pseudomonas aeruginosa has been associated with the presence of certain CFTR mutations. Genomic analysis of the lung microbiome is a young field, but has the potential to define the relationship between lung microbiome composition and disease course. Whether we can manipulate bacterial communities to improve clinical outcomes remains to be seen. PMID- 22318163 TI - Cheyne-Stokes respiration: friend or foe? AB - BACKGROUND: Orthopnoea and paroxysmal nocturnal dyspnoea are common entities regularly confronting thoracic physicians, particularly those with an interest in sleep medicine or non-invasive ventilatory support. One major cause is heart failure (HF), usually associated with abnormal lung function tests, and either obstructive or central sleep apnoea with Cheyne-Stokes respiration (CSA-CSR). Whereas obstructive apnoea is considered injurious to the cardiovascular system, the effects of CSA-CSR are less clear and may be a compensatory response to severe HF. AIM: To determine whether there are compensatory or possibly beneficial aspects caused by CSA-CSR in HF. METHODS: Literature review. RESULTS: CSA-CSR can be detrimental in terms of intermittent hypoxaemia, arousals and autonomic dysregulation. However, it is also associated with the beneficial effects of hyperventilation-related increases in end-expiratory lung volume, intrinsic positive airway pressure, assistance to stroke volume, attenuation of excessive sympathetic nervous activity, avoidance of hypercapnic acidosis and finally the provision of periodic rest to fatigue-prone respiratory pump muscles. CONCLUSIONS: CSA-CSR has physiological features more likely to be compensatory and beneficial than injurious in HF. Some aspects of CSA-CSR are similar to those seen with positive airway pressure. PMID- 22318164 TI - Dihydroxylated 2,4,6-triphenyl pyridines: synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study. AB - Twelve dihydroxylated 2,4,6-triphenyl pyridines were designed and synthesized which contain hydroxyl groups at ortho, meta or para position of 2- and 6-phenyl, or 2- and 4-phenyl rings attached to the central pyridine. They were evaluated for topoisomerase I and II inhibitory activity, and cytotoxicity against several human cancer cell lines for the development of novel anticancer agents. Generally, dihydroxylated 2,4,6-triphenyl pyridines exhibited stronger topoisomerase II inhibitory activity, and cytotoxicity compared to those of monohydroxylated 2,4,6-triphenyl pyridines. The concrete structure-activity relationship was observed that dihydroxylated 2,4,6-triphenyl pyridines with hydroxyl group at meta or para position of 2-phenyl ring displayed significant topoisomerase II inhibitory activity as well as cytotoxicity. Positive correlation between topoisomerase II inhibitory activity and cytotoxicity was observed for compounds 10, 12, 13, 17-20 and 22. PMID- 22318165 TI - Exploration of alpha-aminophosphonate N-derivatives as novel, potent and selective inhibitors of protein tyrosine phosphatases. AB - Seventeen alpha-aminophosphonates are synthesized. Their compositions and structures are established by EA, UV, FT-IR, (1)H NMR, (13)C NMR, (31)P NMR and ESI-MS. Compounds 1-4 are confirmed by X-ray crystallography. PTP inhibition shows compounds 1-5, 12, 15 are moderate competitive inhibitors with some selectivity. The most potent inhibitor is compound 5 with the lowest IC(50) value about 6.64 MUM against PTP1B, about 2-fold and 25-fold stronger than against TCPTP and PTP-MEG2 while it doesn't inhibit SHP-1 and SHP-2. The binding constant of 5 to PTP1B is 2.23 * 10(5) M(-1) and binding ratio approximates 1:1. Cell viability and apoptosis assays indicate 5 is cell permeable with lower cytotoxicity. The results indicate alpha-aminophosphonates are possibly developed to effective and selective inhibitors of PTPs. PMID- 22318166 TI - Synthesis, evaluation and docking studies on 3-alkoxy-4-methanesulfonamido acetophenone derivatives as non ulcerogenic anti-inflammatory agents. AB - A series of 3-alkoxy-4-methanesulfonamido acetophenone derivatives were synthesized and evaluated for their anti-inflammatory activity in carrageenan induced rat paw edema model. The synthesized compounds were also investigated for their gastric ulcerogenic potential. The compounds 4a, 4c and 4d showed comparable anti-inflammatory activity to rofecoxib and indomethacin, the standard drugs taken in both studies and were also non ulcerogenic at the test doses. In silico (docking studies) were done to investigate the hypothetical binding mode of the target compounds to the cyclooxygenase isoenzyme (COX-2). A binding model has been proposed based on the docking studies. Selected physicochemical properties were calculated for theoretical ADME profiling of the compounds and excellent compliance was shown with Lipinski's rules. PMID- 22318169 TI - Ocular gene therapy: introduction to the special issue. PMID- 22318170 TI - A Hybrid Bayesian Network/Structural Equation (BN/SEM) Modeling Approach for Detecting Physiological Networks for Obesity-related Genetic Variants. AB - GWAS studies have been successful in finding genetic determinants of obesity. To translate discovered genetic variants into new therapies or prevention strategies, molecular or physiological mechanisms need to be discovered. One strategy is to perform data mining of data sets with detailed phenotypic data, such as those present in dbGAP (database of Genotypes and Phenotypes) for hypothesis generation. We propose a novel technique that combines the power and computational efficiency of existing Bayesian Network (BN) learning algorithms with the statistical rigor of Structural Equation Modeling (SEM) to produce an overall system that searches the space of potential networks and evaluates promising candidates using standard SEM model selection criteria. We demonstrate our method using the analysis of a candidate SNP data set from the AMERICO sample, a multi-ethnic cross-sectional cohort of roughly three hundred children with detailed obesity-related phenotypes. We demonstrate our approach by showing genetic mechanisms for three obesity-related SNPs. PMID- 22318171 TI - Control of dopants/modifiers in differential mobility spectrometry using a piezoelectric injector. AB - A piezoelectric injector has been interfaced to a differential mobility spectrometer to enable fast and reversible control of dopant/transport-gas modifier levels within the reaction region of the instrument. Operating at 1 Hz with optimised bipolar waveforms for the piezoelectric injector and gas flows within the injector, steady-state 2-butanol mass fluxes of 21 to 1230 ng min(-1) and 1-bromohexane mass fluxes of 149 to 2644 ng min(-1) were delivered to the differential mobility cell. Control of split-flow and transport-gas flow rates enabled rapid and flexible control of the dopant concentrations. The system was consistently reproducible with a relative standard deviation (RSD) of 7.9% at every mass- flux level studied. Stable responses were achieved between 3 to 5 s following a change in the control levels and no significant hysteresis effects were observed. In the positive mode it was possible to control the extent of formation protonated monomer and proton bound cluster ions, tentatively assigned to{C(4)H(9)OH(H(2)O)(n)H}(+) and {(C(4)H(9)OH)(2)(H(2)O)(n)H}(+) and similar control was possible in the negative mode where the concentration relationship for the formation of bromide clusters indicated the presence of multiple ionisation mechanisms. A dopant formulation for the simultaneous control of ions in both the positive and negative modes was demonstrated by the injection of a 50%/50% v/v solution of 2-butanol/1-bromohexane with mass fluxes of 2-butanol in the mixture of between 11 and 1161 ng min(-1) and between 13 and 1325 ng min(-1) for 1-bromohexane. PMID- 22318172 TI - [Editorial. Biochemical recurrence of prostate cancer after radical treatment]. PMID- 22318173 TI - [Biochemical recurrence criteria after radical prostatectomy. Natural history of the disease]. AB - OBJECTIVES: To analyze biochemical recurrence criteria, attending to different PSA-cut-points referred in the literature, and to review prostate cancer natural history. METHODS: Review of the literature through a Medline search. CONCLUSIONS: A PSA of 0.4 ng/ml followed by a value higher than the first, are the values that better define metastatic progression, while a PSA of 0.2 ng/ml followed by a value higher than the first could be more appropriate to define patients about to receive salvage radiotherapy. Nevertheless we need new markers in order to improve prognostic and natural history knowledge. PMID- 22318174 TI - [Biochemical recurrence criteria after radiotherapy (external beam, brachytherapy). Natural history of the disease after radiotherapy]. AB - Prostate specific antigen (PSA) is the main tool in the follow-up of prostate cancer patients after definitive therapy. It's widely used as an early marker to value treatment success. Biochemical recurrence predicts metastatic disease progression and prostate cancer-specific mortality. In 1996, the American Society for Therapeutic Radiology and Oncology (ASTRO) provided a definition of biochemical failure after radiotherapy, based on three consecutive increases in PSA after nadir. As more experience was gained using the proposed definition and follow up duration in the PSA era matured, deficiencies and controversial issues emerged, so more recently proposed candidate definitions have provided consistent outcome. In view of the criticisms, a second consensus conference was held on 2005, with "nadir + 2 ng/ml" accepted as standard definition. The natural history and evidence of PSA kinetic parameters and different definitions of biochemical failure after external beam radiation therapy and/or brachytherapy are reviewed in the following article. PMID- 22318175 TI - [PSA bounce phenomenon after local treatment with radiation for prostate cancer]. AB - Radiotherapy is a curative treatment for localized prostate cancer in its modalities of brachytherapy (BT) and external beam radiotherapy (EBRT). A temporary increase in prostate-specific antigen (PSA) values following a radiotherapy treatment coupled with a decrease without therapeutic intervention may happen in 30% of the patients. This phenomenon is known as PSA bounce and lacks prognostic effect in relation to tumor control. Additionally, it produces anxiety in the patient because of the fear of failure, and in the physicists due to the uncertainty about the state of the tumor. The etiology and pathogenesis are still unknown. Several factors associated with the tumor and the treatments have been evaluated in the studies which analyze this phenomenon, the age is the only observed factor with the highest consistency as a bounce predictor. The definition of biologic failure (BF)after EBRT or BT with or without androgenic deprivation (ADT) according to Phoenix criteria, which considers an increase of at least 2 ng/ml over PSA nadir, enables better taking the bounce phenomenon into account, although is not free from false BF that may affect to the relapse-free survival in patients with follow-up shorter than 3 years. PMID- 22318176 TI - [Predictive models for biochemical recurrence of prostate cancer after local treatment. Nomograms]. AB - In this narrative review we present the concept of nomogram in the context of predictive models in prostate cancer. In fact we try to answer the following questions from a practical and critical point of view: What is a nomogram? How to read and evaluate nomograms? What nomograms predict biochemical relapse in prostate cancer after local treatment, either surgery or radiotherapy? Why are nomograms better than risk groups stratification? And, finally, why don't clinicians use nomograms in fact? PMID- 22318177 TI - [Imaging diagnosis for prostate cancer biochemical recurrence after radical treatment]. AB - The recent development in the imaging diagnostic techniques have improved the diagnosis of prostate cancer recurrence, mainly if it is local. Nowadays, the use of MRI based morphologic and functional techniques has a better sensitivity for the diagnosis of local recurrence. Integration of MR imaging data with ultrasound guided transrectal biopsies has improved the accuracy in the diagnosis of local recurrence of the disease. However, there is a need for new or better methods that enable the detection of secondary systemic disease, the conventional methods being (CT and bone scintigraphy) insufficiently sensitive. Nowadays the PET-CT is the most promising technique, for which the use of new radio-pharmaceuticals (on experimental phases) would allow the diagnosis of systemic disease more accurately. The combined and complimentary use of the different imaging techniques available, will permit to diagnose relapsing disease earlier and better, setting the field up for more adequate treatments, reducing morbility and giving the opportunity to offer local, less aggressive treatments. PMID- 22318178 TI - [Molecular markers as predictive factors biochemical failure after radical treatment of prostate cancer]. AB - Clinical nomograms based on Gleason grade, tumor stage, and serum PSA are still the best predictors of prostate cancer (PC) outcome. The biotechnological advancements achieved in the last decade represent a remarkable source for new prognostic and predictive tissue and serum molecular biomarkers. In this review, we will summarize conventional PC prognostic biomarkers and focus on novel identified biomarkers for PC early diagnosis and progression that might be used in the future. Although they are not ready for widespread, routine use, there are reasons to believe that future models will combine these markers with traditional pretreatment and treatment-related variables and will improve our ability to predict outcome and select the optimal treatment. PMID- 22318179 TI - [Management of prostate cancer biochemical recurrence in the clinical guidelines]. AB - OBJECTIVE: Review of the Guidelines which have major impact on the urological field, in order to compare and to know their recommendations in the diagnosis and management of biochemical relapse after a healing treatment of prostate cancer (radical prostatectomy or radiotherapy). METHODS: We review the Guidelines of the European Urological Association (EAU), the American Urological Association (AUA), of the National Comprehensive Cancer Network (NCCN) and those of the National Institute for Health and Clinical Excellence (NICE), as well as the scientific evidence on which they are based. RESULTS: In this paper we state the complexity of the subject being dealt with and coincidences and differences among them. The definition of relapse varies depending on whether the patient has undergone either radical prostatectomy or radiotherapy. Regarding treatment, in the first case early radiotherapy is the treatment of choice, but recommendations after radiotherapy are not so specific. CONCLUSION: Clinical Guidelines represent a great aid in decision making for the professional. Guidelines give recommendations with a higher o lower degree of scientific evidence and must be evaluated regularly to include new evidences which are coming through. PMID- 22318180 TI - [Radical prostatectomy after radiotherapy]. AB - Radical prostatectomy is an excellent salvage method for patients with prostatic cancer when radical radiotherapy or brachytherapy fail. To define local failure is not always reliable; nevertheless, performing a prostatic biopsy two years after treatment could reach an early diagnosis. Another accepted attitude is to perform the biopsy after biochemical recurrence, but sometimes the pathological stage is already locally advanced tumor. It is also difficult to determine which patients are suitable for this rescue treatment, probably those with locally confined tumors and with favorable PSA kinetics, PSA velocity below 2.0 or a PSA doubling time over 12 months, and in whom detectable PSA is reached 2 years after treatment. These patients are suitable for radical prostatectomy if they have a live expectancy of more than 10 years. Although rescue radical prostatectomy has a higher rate of complications and worse functional results, cancer-specific survival rates are high, and remain high after 15 years of follow-up. Currently, new surgical improvements and new radiotherapy technology are diminishing surgical complications and improving functional results. In summary radical prostatectomy is a feasible rescue procedure after radiotherapy failure although the complications rate remains higher than prostatectomy as initial therapy. PMID- 22318181 TI - [Rescue cryotherapy for prostate cancer after radiotherapy]. AB - Radical Radiotherapy constitutes a useful therapeutic option for localized prostate cancer. Almost one third of prostate cancer patients choose this alternative to treat the disease. Despite modifications in the technique as intensity modulation, 3D conformational radiotherapy or computer-assisted brachytherapy, a significant percentage of these patients will show an increase in PSA values after radiation. Local relapse without distant disease and PSA less than 10 ng/ml are candidates for salvage therapy. Cryotherapy has already become a curative treatment option in this group of patients. Recent technological as well as surgical advances in salvage-cryotherapy have reduced dramatically complications and progressively increase the interest on this alternative. PMID- 22318182 TI - [Salvage high energy focalized ultrasound (HIFU) in prostate cancer after radiotherapy]. AB - OBJECTIVES: To evaluate the efficacy and safety of High Intensity Focused Ultrasound (HIFU) as salvage treatment after radical radiotherapy in prostate cancer (PC). METHODS: We reviewed the literature through databases and published articles that refer to this treatment between 2000 and 2010. We evaluated oncological results and adverse effects, compared with those published in conjunction with other therapies. RESULTS: We evaluated the different series, which include the results of the two devices currently available, all with their initial results and those that are in the process of dose adjustment. Generally, it can be said that the biggest problem of all is that initial morbidity is reduced as the surgeon gains experience with the treatment. We must stress the importance of the short series that are evaluated, especially in follow-up time and number of patients. Also, except for a recently published systematic review, no prospective studies are published. The results from different series are compared with existing literature regarding to other PC treatments. CONCLUSIONS: In spite of published results, the treatment with HIFU for prostate cancer recurrence after radiotherapy is an option that should be considered. Especially considering that, it is important to delay the development of the disease in these patients, and there are no other alternatives that have proven to be effective. Further research is needed to explore the use of HIFU in the treatment of PC. Anyway, it is essential to publish comparative prospective series and series with more patients and longer follow-up to draw definitive conclusions. PMID- 22318183 TI - [Hormonal treatment in biochemical recurrence after radical prostatectomy]. AB - To date, the role of hormonal therapy (HT) after biochemical failure, when to initiate it, the therapeutic scheme and duration remains controversial due to the absence of well designed randomized trials analyzing the overall survival of patients. In clinical practice, the most widely spread treatment in this scenario is hormonal therapy with LH-RH analogues. However, the scientific support for this issue is very weak. We are extrapolating the benefits proven for early vs delayed HT in advanced prostate cancer, to asymptomatic patients presenting just an increase in PSA. These patients usually have a long time disease-history until development of metastasis. It should also be noticed the harmful secondary effects acquired with the time of employment of hormotherapy. Probably patients suffering a Gleason score >8 and PSA doubling time <12 months could obtain a benefit from an early castration treatment, even more if they are young (grade 2c). Except in selected cases of local treatment as radiotherapy, the decision for early or delayed hormonal therapy should be taken carefully with patient consensus. The alternatives for hormonal treatment to preserve sexual function, as intermittent treatment, antiandrogen monotherapy, or antiandrogen plus 5 alpha reductase inhibitors, are very attractive in this scenario. However due to the short time experience with these modalities of treatment should be evaluated with caution. PMID- 22318184 TI - [Salvage external beam radiotherapy for prostate cancer biochemical recurrence after radical prostatectomy]. AB - We review salvage external beam radiotherapy for biochemical recurrence after radical prostatectomy. Having defined recurrence, we analyze the risk factors of local recurrence and systemic evaluation of patients scheduled to undergo salvage radiotherapy. New techniques in external radiation, doses and volumes help us to define the areas minimizing treatment toxicity and improving the quality of the patient. We analyzed the literature to improve the therapeutic approach, based on currently known data, pending completion of further clinical trials. We describe a review about radiotherapy in biochemical failure after radical prostatectomy. PMID- 22318185 TI - [Salvage brachytherapy for prostate cancer biochemical recurrence after radiotherapy]. AB - The best treatment option for patients with prostate cancer who experience local relapse after external beam radiation therapy remains uncertain. Salvage brachytherapy, cryotherapy, HIFU and radical prostatectomy have shown varying biochemical and quality-of-life outcomes according to disease-related and patient related factors, but follow-up data are still short. It seems clear that careful patient selection for salvage brachytherapy is essential for good clinical and quality-of-life outcomes. We present a review of the currently available experiences of brachytherapy as salvage treatment after failure to external beam radiotherapy. PMID- 22318186 TI - [Risk factors for biochemical recurrence after radical prostatectomy in patients with clinically localized prostate cancer. Implications of adjuvant treatment]. AB - To evaluate the pathological variables predictive of biochemical recurrence after radical prostatectomy and their implications for decision making in the adjuvant setting. METHODS: 684 patients with localized prostate cancer who were treated with radical prostatectomy between 1996 and 2007. Before surgery they were classified according to D'Amico risk groups for recurrence. Following prostatectomy the following variables were collected: Gleason score, pathological stage, capsular invasion, surgical margins, perineural invasion and percentage of involvement in the piece. Univariate analysis was performed and subsequently adjusted using a Cox proportional hazards model (method enter). RESULTS: The median follow up of the series was 61 months. 29.1% of patients had biochemical recurrence. Overall mortality of the series was 4.9% and cancer-specific mortality 1.2%. In univariate analysis the Gleason score of surgical specimens, capsular invasion, perineural invasion, involvement of surgical margins, pathological stage and percentage of involvement of the piece had statistically significant (p <0.001) relation with biochemical recurrence. In multivariate analysis, a Gleason score >= 8 in the surgical specimen (HR = 3.08), existence of affected surgical margins (HR = 2.98), pT3 stage (HR = 1.61) and involvement of more than 50% of the piece by cancer (HR = 3.39) were identified as independent predictors of biochemical recurrence. Stratifying by independent predictors of biochemical recurrence (pT, Gleason score and margin), patients with at least 2 of these factors had an incidence of biochemical recurrence at 5 years exceeding 50%. CONCLUSIONS: Patients who have a Gleason score >= 8, positive margins, pT3 tumour or a percentage of >50% after prostatectomy have an increased risk of biochemical recurrence. Patients with at least 2 predictors of relapse have a probability of recurrence over 50% in the first 5 years of recurrence and should therefore be candidates for adjuvant radiotherapy. PMID- 22318187 TI - [Incidence and prognostic factors for biochemical recurrence after radical radiotherapy]. AB - OBJECTIVES: The aim of this study is to analyze the outcomes obtained after External-Beam Radiotherapy (3D EBRT)in patients with prostate cancer. METHODS: The study includes 503 patients (p) treated at the Hospital General Universitario Gregorio Maranon in Madrid, diagnosed between 2000-2007, with low, intermediate or high risk prostate cancer (D'Amico risk groups), treated with 3D EBRT. Biochemical recurrence (BR) was defined as nadir +2 following Phoenix's criterion. The median follow-up was 59 months (range 3.4-104.2). RESULTS: Biochemical relapse-free survival (bRFS) rates at 5 and 8 years were 88 +/- 2% and 76 +/- 3%, respectively. Multivariate analysis indicated initial PSA (p <0.02), perineural invasion in biopsy specimen (p <0.00), EBRT dose (p = 0.01) and the use of androgen deprivation therapy (ADT)(p = 0.00) to be independent predictors of relapse. Nadir PSA value <0.3 ng/ml was associated with the best 5 year bRFS (96.6% versus 56.5% if nadir PSA > 1.3 ng/ml). Late urinary and rectal toxicity >= 3 was lower than 5%. Active rescue treatment was indicated in 85% of patients. Only 10 patients died of prostate cancer. CONCLUSION: The biochemical failure rate is determined by classical pretreatment features (initial PSA level, risk group, perineural invasion) and low- dose EBRT (<= 72 Gy), nadir PSA value and the use of ADT in intermediate and high risk groups. PMID- 22318188 TI - [Biochemical recurrence in patients with prostate cancer after radical treatment. Comparative study of prostatectomy vs. radiotherapy]. AB - OBJECTIVES: To compare the biochemical relapse-free survival between radical prostatectomy and radiotherapy in patients with localized prostate cancer of low and intermediate recurrence risk. METHODS: A retrospective study of 435 patients with localized prostate cancer, radical prostatectomy was performed in 65% of patients and radiotherapy was in 35%. The Kaplan-Meier Estimator was used to assess the biochemical relapse-free survival and long-rank test, Breslow and Tarone-Ware to evaluate the differences between the groups with confidence intervals at 95%. RESULTS: The median follow-up of the series was 60 months (3 106). Biochemical recurrence was diagnosed in 21% of patients: 22% of those were treated with prostatectomy and 19% with radiotherapy (p = 0.47). No significant differences were observed according to risk group (p = 0.60 in the low risk and p = 0.32 in the intermediate risk). Tree, five and seven-year actuarial biochemical recurrence-free survival for prostatectomy were 84%, 75%and 70%, while for radiotherapy were 97%, 84% and 64% respectively. CONCLUSIONS: There are no significant differences in actuarial biochemical recurrence free survival in patients with localized prostate cancer of low and intermediate risk treated with prostatectomy or radiation therapy. Due to the crossing of the survival curves we do not rule out that with longer follow-up these results could be modified. PMID- 22318189 TI - [Treatment of the patient with castration-resistant biochemical progression of prostate cancer]. AB - Castration resistant prostatic carcinoma (CRPC) is defined as tumor progression despite an effective castration (serum testosterone levels < 50 ng/dL). Biochemical progression requires at least two successive increases from the previous lowest value of serum prostate-specific antigen (PSA) spaced at least a week, and with a minimum value of 2 ng/mL. In patients receiving complete androgen blockade, antiandrogen should be discontinued prior to diagnosis of CRPC. CPRC is a heterogeneous entity. Baseline PSA and PSA velocity seem to be the most important prognostic factors in patients with biochemical relapse as the only manifestation of CRPC. Some of these patients can be followed without treatment until disease progression. Because of a large proportion of tumors progressing under androgen deprivation therapy remain hormone-dependent, the use of other hormonal therapies has been the preferred treatment for the majority of these patients. Besides inhibitors of adrenal steroidogenesis, other novel hormonal approaches are currently under investigation to avoid the effect of the activated androgenic receptor on the tumor cell. In recent years there has been an important development of immunotherapy, which has demonstrated to increase survival in CRPC oligosymptomatic patients. First and second line chemotherapy in CRPC are associated with an increase in overall survival, but they are usually recommended for patients with metastases. Until the results of ongoing trials are available, the type and timing of the treatment for patients with CRPC and biochemical recurrence should be individualized. PMID- 22318190 TI - [Quality of life after biochemical recurrence in patients with prostate cancer. How and how long do patients live after biochemical recurrence?]. AB - Routine monitoring of PSA in patients with localized prostate cancer radically treated permits to identify those with biochemical recurrence only. Treatment options for biochemical failure include observation, surgery, radiotherapy alone or combined with hormonal therapy, brachytherapy, cryotherapy and hormone therapy exclusively. These treatments determine a specific pattern of changes (urinary function, bowel, sexual and hormonal) that can negatively impact the quality of life, so that the indication must be made in a judicious way and always in consonance with patient's expectations and preferences. Decisions on how and when to treat biochemical failure are complicated and the impact of salvage therapy on clinical outcome is unknown. Rates of prostate cancer control after salvage therapy with prostatectomy, brachytherapy or cryotherapy vary between 20-80% of cases according to selected patient characteristics. Because individuals with BF may be clinically asymptomatic for many years without treatment, it is essential that physicians and patients have a clear understanding of the potential impact of these on the quality of life. PMID- 22318191 TI - Effect of 12-week administration of 20-mg long-acting methylphenidate on Glu/Cr, NAA/Cr, Cho/Cr, and mI/Cr ratios in the prefrontal cortices of school-age children in Indonesia: a study using 1H magnetic resonance spectroscopy (MRS). AB - OBJECTIVES: Recent studies on the neurobiology of attention-deficit/hyperactivity disorder (ADHD) have suggested that there is dysregulation of dopamine-mediated neurotransmission, particularly in the prefrontal cortex and basal ganglia, and that treatment with methylphenidate reverses this dysregulation. Using methodology similar to previous studies involving putative markers of brain functioning, we used 1H magnetic resonance spectroscopy to study the effect of 12 week treatment with daily 20-mg long-acting methylphenidate on the glutamate/creatine, N-acetyl-aspartate/creatine, choline/creatine, and myoinositol/creatine ratios in the prefrontal cortices of medication-naive children with ADHD. METHOD: This was a prospective study, using a pretest and posttest design, on a single group of 21 children (mean age, 8.52 years; 17 males and 4 females) with a diagnosis of ADHD. A low time echo (TE) magnetic resonance spectroscopic scans sampled voxels of interest (1.5 * 1.5 * 2.0) from both the right and left prefrontal cortices. RESULTS: After treatment, the N-acetyl aspartate/creatine ratio increased 18.8% in the right prefrontal cortex (P = 0.001) and 10% in the left prefrontal cortex (P = 0.007); the glutamate/creatine ratio decreased 15% in the right prefrontal cortex (P = 0.005) and 14.1% in the left prefrontal cortex (P = 0.005); the choline/creatine ratio decreased 12.4% in the right prefrontal cortex (P = 0.037) and 16% in the left prefrontal cortex (P = 0.006); and the myoinositol/creatine ratio decreased 14.7% in the left prefrontal cortex (P = 0.011) and 7.7% in the right prefrontal cortex (P = 0.129). CONCLUSION: Notwithstanding the limitations of this pilot study, we found, after stimulant treatment, significant neurochemical changes (thought to reflect functional improvement and improved neuroplasticity) in the prefrontal cortices of children with ADHD. PMID- 22318192 TI - Sustained efficacy of natalizumab in the treatment of relapsing-remitting multiple sclerosis independent of disease activity and disability at baseline: real-life data from a Swiss cohort. AB - OBJECTIVES: Therapy for relapsing-remitting multiple sclerosis with natalizumab (Tysabri; Biogen Idec) has been shown to be effective in the reduction of the clinical relapse rate and disability progression. However, real-life longitudinal data, including years before baseline, are rare. METHODS: An observational single center study was carried out. We analyzed data from 64 consecutive patients with multiple sclerosis. RESULTS: After 1 year of treatment (n = 64), score on the Expanded Disability Status Scale (EDSS) decreased by 0.47 points (P = 0.047) and the annualized relapse rate (ARR) decreased by 82% (P < 0.001). After 2 years (n = 41), EDSS score was still reduced by 0.28 (not significant) and ARR was reduced by 69% (P < 0.001). After 3 years (n = 23), EDSS score was reduced by 0.26 (not significant), and ARR was reduced by 77% (P < 0.001). Reduction of EDSS score and ARR did not depend on baseline ARR (1-2 vs >2) or EDSS score and was not biased by exceptional high disease activity or relapses around baseline. CONCLUSIONS: These real-life data reinforce that natalizumab is effective over years, reduces ARR, and stabilizes EDSS score independent of baseline ARR, baseline EDSS score, or baseline treatment. PMID- 22318193 TI - Pramipexole may be an effective treatment option in essential tremor. AB - OBJECTIVES: To perform a pilot study assessing possible efficacy, safety, and optimal dosage of pramipexole in essential tremor. METHODS: Twenty-nine patients with essential tremor were enrolled into this 16-week-long study. After recording baseline condition, 2 different dosages of immediate-release formulation of pramipexole were evaluated (1.05 mg/d and 2.1 mg/d in 3 identical dosages). Subsequently, immediate- and extended-release formulations were compared. The Fahn-Tolosa-Marin Tremor Rating Scale, Activities of Daily Living, the EuroQol instrument for detecting health-related outcome, and Clinical Global Impression of Improvement Scale were obtained. After completing the study, a rater blinded to the treatment reassessed the tremor rating scales based on video recordings. RESULTS: Twenty-four patients (82.6%) completed the study. Causes for discontinuation were adverse effects of pramipexole: intolerable nausea (n = 3), daytime sleepiness (n = 1), and anxiety (n = 1). Twenty-one patients had a score of less than 3 on the Clinical Global Impression of Improvement Scale (treatment responders, 72.4%). All the major outcome values demonstrated significant improvement. The severity of tremor was reduced by 52.0% (43.7 vs 20.8 points, Fahn-Tolosa-Marin Tremor Rating Scale), and the EuroQol instrument for detecting health-related outcome score improved from 0.69 to 0.91 (P < 0.01). The dose of 2.1 mg was more effective than that of 1.05 mg; however, both the immediate- and extended-release formulations were equally efficacious. After completion of the study, 15 patients (51.7% of the enrolled patients) wanted to remain on pramipexole treatment. CONCLUSIONS: This pilot study suggests that pramipexole may be effective in the treatment of essential tremor. However, further controlled studies are required. PMID- 22318195 TI - Reduced gamma-aminobutyric acid in occipital and anterior cingulate cortices in primary insomnia: a link to major depressive disorder? AB - Insomnia is closely related to major depressive disorder (MDD) both cross sectionally and longitudinally, and as such, offers potential opportunities to refine our understanding of the neurobiology of both sleep and mood disorders. Clinical and basic science data suggest a role for reduced gamma-aminobutyric acid (GABA) in both MDD and primary insomnia (PI). Here, we have utilized single voxel proton magnetic spectroscopy (1H-MRS) at 4 Tesla to examine GABA relative to total creatine (GABA/Cr) in the occipital cortex (OC), anterior cingulate cortex (ACC), and thalamus in 20 non-medicated adults with PI (12 women) and 20 age- and sex-matched healthy sleeper comparison subjects. PI subjects had significantly lower GABA/Cr in the OC (p=0.0005) and ACC (p=0.03) compared with healthy sleepers. There was no significant difference in thalamic GABA/Cr between groups. After correction for multiple comparisons, GABA/Cr did not correlate significantly with insomnia severity measures among PI subjects. This study is the first to demonstrate regional reductions of GABA in PI in the OC and ACC. Reductions in GABA in similar brain regions in MDD using 1H-MRS suggest a common reduction in cortical GABA among PI and mood disorders. PMID- 22318196 TI - Physical exercise and antidepressants enhance BDNF targeting in hippocampal CA3 dendrites: further evidence of a spatial code for BDNF splice variants. AB - Brain-derived neurotrophic factor (BDNF) is encoded by multiple BDNF transcripts, whose function is unclear. We recently showed that a subset of BDNF transcripts can traffic into distal dendrites in response to electrical activity, while others are segregated into the somatoproximal domains. Physical exercise and antidepressant treatments exert their beneficial effects through upregulation of BDNF, which is required to support survival and differentiation of newborn dentate gyrus (DG) neurons. While these DG processes are required for the antidepressant effect, a role for CA1 in antidepressant action has been excluded, and the effect on CA3 neurons remains unclear. Here, we show for the first time that physical exercise and antidepressants induce local increase of BDNF in CA3. Voluntary physical exercise for 28 consecutive days, or 2-week treatment with 10 mg/kg per day fluoxetine or reboxetine, produced a global increase of BDNF mRNA and protein in the neuronal somata of the whole hippocampus and a specific increase of BDNF in dendrites of CA3 neurons. This increase was accounted for by BDNF exon 6 variant. In cultured hippocampal neurons, application of serotonin or norepinephrine (10-50 MUM) induced increase in synaptic transmission and targeting of BDNF mRNA in dendrites. The increased expression of BDNF in CA3 dendrites following antidepressants or exercise further supports the neurotrophin hypothesis of antidepressants action and confirms that the differential subcellular localization of BDNF mRNA splice variants provides a spatial code for a selective expression of BDNF in specific subcellular districts. This selective expression may be exploited to design more specific antidepressants. PMID- 22318197 TI - Modulation of social influence by methylphenidate. AB - The ability to infer value from the reactions of other people is a common and essential ability with a poorly understood neurobiology. Commonly, social learning matches one's values and behavior to what is perceived as normal for one's social group. This is known as conformity. Conformity of value correlates with neural activity shared by cognitions that depend on optimum catecholamine levels, but catecholamine involvement in conformity has not been tested empirically. Methylphenidate (MPH) is an indirect dopamine and noradrenalin agonist, commonly used for the treatment of attention-deficit hyperactivity disorder for which it reduces undesirable behavior as evaluated by peers and authority figures, indicative of increased conformity. We hypothesized that MPH might increase conformity of value. In all, 38 healthy adult females received either a single oral 20 mg dose of MPH or placebo (PL). Each subject rated 153 faces for trustworthiness followed immediately by the face's mean rating from a group of peers. After 30 min and a 2-back continuous-performance working-memory task, subjects were unexpectedly asked to rate all the faces again. Both the groups tended to change their ratings towards the social norm. The MPH group exhibited twice the conformity effect of the PL group following moderate social conflict, but this did not occur following large conflicts. This suggests that MPH might enhance signals that would otherwise be too weak to evoke conformity. MPH did not affect 2-back performance. We provide a new working hypothesis of a neurocognitive mechanism by which MPH reduces socially disruptive behavior. We also provide novel evidence of catecholamine mediation of social learning [corrected]. PMID- 22318198 TI - Trait impulsive choice predicts resistance to extinction and propensity to relapse to cocaine seeking: a bidirectional investigation. AB - Despite the strong association between impulsivity and addiction in humans, it is still a matter of debate whether impulsive choice predisposes to, or results from, drug dependence. Furthermore, it is unknown whether treating impulsivity can protect against relapse propensity. Therefore, this study explored the bidirectional relationship between impulsive choice and cocaine taking and seeking in rat behavioral models. In experiment 1, to determine whether impulsive choice predisposes to cocaine taking or seeking, rats were selected based on trait impulsivity in a delayed reward task and subsequently compared on various stages of cocaine self-administration (SA). To examine the consequence of cocaine intake on impulsive choice, impulsivity was monitored once a week throughout various stages of cocaine SA. To determine whether treating impulsive choice can protect against relapse propensity, in experiment 2, impulsive choice was manipulated by pharmacological interventions and cocaine-associated contextual cues. Trait impulsive choice as determined in experiment 1 predicted high extinction resistance and enhanced propensity to context-induced relapse in the cocaine SA model, whereas cocaine intake did not alter impulsive choice. Furthermore, acute changes in impulsive choice were not related to rates of context-induced relapse. Taken together, the current data indicate that trait impulsive choice predicts persistent cocaine seeking during extinction and enhanced propensity to relapse, whereas acute manipulations of impulsive choice had no favorable outcomes on relapse measures. These observations suggest that trait impulsivity can be used as a predictive factor for addiction liability, but treating this impulsivity does not necessarily protect against relapse. PMID- 22318200 TI - Quantitative differences in HTLV-I antibody responses: classification and relative risk assessment for asymptomatic carriers and ATL and HAM/TSP patients from Jamaica. AB - Adult T-cell leukemia (ATL) and human T-cell lymphotropic virus type I (HTLV-I) associated myelopathy/tropical spastic paraparesis (HAM/TSP) are known to be caused by HTLV-I infection. However, current methods used to determine HTLV-I infection do not differentiate between HTLV-I asymptomatic carriers (ACs) and ATL and HAM/TSP patients. Using the luciferase immunoprecipitation system, a highly sensitive, quantitative technology that can efficiently detect HTLV-I Ab responses, we examined Ab responses for HTLV-I in serum/plasma samples from 439 subjects in Jamaica, including HTLV-I-seronegative donors, ACs, and ATL and HAM/TSP patients. The Ab responses of HTLV-I-infected subjects differed significantly from those of seronegative donors for all 3 immunodominant proteins, Gag, Env, and Tax. HAM/TSP patients had significantly higher Ab responses for Gag and Env compared with ACs, and Ab responses for all 3 Ags were higher in HAM/TSP patients than in ATL patients. Moreover, immunoreactivities for HTLV-I Ags as determined by the luciferase immunoprecipitation system could distinguish HAM/TSP patients from ACs at a true-positive rate of 85.42% and from ATL patients at a true-positive rate of 75.00%, and modeled in conjunction with subject information to distinguish HAM/TSP patients from ACs (odds ratio = 14.12) and from ATL patients (odds ratio = 7.00). The relative risk assessment resulting from these significant differences between Ab responses in HTLV-I-infected groups may be a useful diagnostic tool in the future. PMID- 22318199 TI - Stroke With Transfusions Changing to Hydroxyurea (SWiTCH). AB - Stroke is a devastating complication of sickle cell anemia (SCA) with high recurrence if untreated. Chronic transfusions reduce recurrent strokes but have associated morbidities including iron overload. Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) was a multicenter phase 3 randomized trial comparing standard treatment (transfusions/chelation) to alternative treatment (hydroxyurea/phlebotomy) for children with SCA, stroke, and iron overload. SWiTCH was a noninferiority trial with a composite primary end point, allowing an increased stroke risk but requiring superiority for removing iron. Subjects on standard treatment received monthly transfusions plus daily deferasirox iron chelation. Subjects on alternative treatment received hydroxyurea plus overlap transfusions during dose escalation to maximum tolerated dose (MTD), followed by monthly phlebotomy. Subjects on standard treatment (N = 66) maintained 30% sickle hemoglobin (HbS) and tolerated deferasirox at 28.2 +/- 6.0 mg/kg/d. Subjects on alternative treatment (N = 67) initiated hydroxyurea and 60 (90%) reached MTD at 26.2 +/- 4.9 mg/kg/d with 29.1% +/- 6.7% fetal hemoglobin (HbF). Adjudication documented no strokes on transfusions/chelation but 7 (10%) on hydroxyurea/phlebotomy, still within the noninferiority stroke margin. The National Heart, Lung, and Blood Institute closed SWiTCH after interim analysis revealed equivalent liver iron content, indicating futility for the composite primary end point. Transfusions and chelation remain a better way to manage children with SCA, stroke, and iron overload. PMID- 22318201 TI - Perspectives on chronic inflammation in essential thrombocythemia, polycythemia vera, and myelofibrosis: is chronic inflammation a trigger and driver of clonal evolution and development of accelerated atherosclerosis and second cancer? AB - The morbidity and mortality of patients with the chronic Philadelphia-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia, polycythemia vera, and primary myelofibrosis are mainly caused by cardiovascular diseases, thrombohemorrhagic complications, and bone marrow failure because of myelofibrosis and leukemic transformation. In the general population, chronic inflammation is considered of major importance for the development of atherosclerosis and cancer. MPNs are characterized by a state of chronic inflammation, which is proposed to be the common denominator for the development of "premature atherosclerosis," clonal evolution, and second cancer in patients with MPNs. Chronic inflammation may both initiate clonal evolution and catalyze its expansion from early disease stage to the myelofibrotic burnt-out phase. Furthermore, chronic inflammation may also add to the severity of cardiovascular disease burden by accelerating the development of atherosclerosis, which is well described and recognized in other chronic inflammatory diseases. A link between chronic inflammation, atherosclerosis, and second cancer in MPNs favors early intervention at the time of diagnosis (statins and interferon-alpha2), the aims being to dampen chronic inflammation and clonal evolution and thereby also diminish concurrent disease-mediated chronic inflammation and its consequences (accelerated atherosclerosis and second cancer). PMID- 22318202 TI - TCR affinity and specificity requirements for human regulatory T-cell function. AB - We investigated whether TCRs restricted to the more ubiquitously expressed MHC class I molecules could be used to redirect human regulatory T cells (Tregs). Using a series of HLA-A2-restricted TCRs that recognize the same peptide-MHC class I complex (pMHC) with affinities varying up to 3500 fold, we observed that TCR affinity had no effect on the ability of the introduced TCRs to confer potent Ag-specific suppressive activity. Surprisingly, we found a naturally occurring, low-affinity MHC class I-restricted TCR specific for an NY-ESO-1 epitope that was unable to redirect a functional CD4 T-effector cell response could confer potent antigen-specific suppressive activity when expressed in Tregs and severely impair the expansion of highly functional HIV-1(GAG)-specific CD8 T cells expressing a high-affinity TCR. This suppressive activity was only observed when both Ags were presented by the same cell, and no suppression was observed when the target Ags were put in distinct cells. These studies underscore the clinical utility of using MHC class I-restricted TCRs to endow Tregs with specificity to control autoimmune disease and highlight the conditions in which this approach would have most therapeutic benefit. PMID- 22318203 TI - Functional features of RUNX1 mutants in acute transformation of chronic myeloid leukemia and their contribution to inducing murine full-blown leukemia. AB - The BCR-ABL fusion protein generated by t(9;22)(q34;q11) in chronic myeloid leukemia (CML) plays an essential role in the pathogenesis of the myeloproliferative disorder status at the chronic phase of the disease, but progression from the chronic phase to blast crisis (BC) is believed to require additional mutations. To explore the underlying mechanisms for BC, which is characterized by a blockage of blood cell differentiation, we screened several genes crucial to hematopoiesis and identified 10 types of mutations in RUNX1 among 11 of 85 (12.9%) patients with acute transformation of CML. Most of the mutations occurred in the runt homology domain, including H78Q, W79C, R139G, D171G, R174Q, L71fs-ter94, and V91fs-ter94. Further studies indicated that RUNX1 mutants not only exhibited decreased transactivation activity but also had an inhibitory effect on the WT RUNX1. To investigate the leukemogenic effect of mutated RUNX1, H78Q and V91fs-ter94 were transduced into 32D cells or BCR-ABL harboring murine cells, respectively. Consistent with the myeloblastic features of advanced CML patients with RUNX1 mutations, H78Q and V91fs-ter94 disturbed myeloid differentiation and induced a BC or accelerated phase-like phenotype in mice. These results suggest that RUNX1 abnormalities may promote acute myeloid leukemic transformation in a subset of CML patients. PMID- 22318204 TI - Association of severe hypertension with pneumonia in elderly patients with acute ischemic stroke. AB - Pneumonia is one of the most frequent complications in elderly patients with acute ischemic stroke. Although severe hypertension is often observed in the early phase of acute stroke, there are few studies of acute hypertension as a factor influencing the incidence of stroke-associated pneumonia (SAP) in elderly subjects with acute ischemic stroke. To assess the association of acute phase blood-pressure elevation with the incidence of SAP, we compared 10 elderly patients with acute ischemic stroke complicated with severe hypertension (>= 200/120 mm Hg) with 43 patients with moderate hypertension (160-199/100-119 mm Hg), as well as with 65 control normotensive or mildly hypertensive (<160/100 mm Hg) controls on admission. Data were collected on known risk factors, type of ischemic stroke and underlying chronic conditions. The significance of differences in risk factors was analyzed using univariate and multivariate comparisons of 38 SAP cases and others, 8 SAP death cases and others, and 28 patients with poor outcome associated with in-hospital death or artificial feeding at discharge and others. After adjustment for potential confounding factors, the relative risk estimates for SAP, SAP death and poor outcome were 2.83 (95% confidence interval 1.14-7.05), 5.20 (1.01-26.8) and 6.84 (1.32-35.4), respectively, for severe hypertension relative to normotensive or mildly hypertensive controls. We conclude that severe hypertension on admission is an independent predictive factor for SAP in elderly patients with acute ischemic stroke. PMID- 22318205 TI - Short-term ACE inhibition confers long-term protection against target organ damage. AB - Angiotensin converting enzyme (ACE) inhibitors reduce left ventricular (LV) hypertrophy and cardiovascular-renal fibrosis. Experimentally, changes in the LV and kidney persist even after cessation of treatment. The present study investigates whether brief ACE inhibition in spontaneously hypertensive rats (SHR) provides long-term protection against the LV and kidney damage induced by the nitric oxide synthase inhibitor N-omega-nitro-L-arginine-methyl ester (L NAME). SHR received the ACE inhibitor enalapril (n = 36) or tap water (n = 36). In all, 12 control and treated SHR were sacrificed after 2 weeks and remaining rats were taken off-treatment. After a 2-week washout, 12 controls or previously treated SHR were sacrificed and remaining rats were treated with L-NAME ((control (Con)+L, enalapril (Enal)+L) for 10 days. At sacrifice, blood pressure was recorded via carotid artery cannulation in anesthetized rats, and blood, the kidney and LV were isolated for analysis. LV mass and arterial pressure were significantly reduced by enalapril. LV mass showed a persistent reduction throughout the study. In LV, prior enalapril treatment provided significant (P<0.05) protection against L-NAME-induced increases in proliferating cells (Con+L: 11 +/- 10.0 mm(2) vs. Enal+L: 4 +/- 4.4 mm(2)), interstitial fibrosis (Con+L: 3 +/- 2.5% vs. Enal+L: 1 +/- 1.0%) and tissue macrophages (Con+L: 12 +/- 9 mm(2) vs. Enal+L: 5 +/- 3.6 mm(2)). In the kidney, prior enalapril treatment protected against L-NAME-induced interstitial fibrosis and vascular injury. There was no difference in glomerular size or glomerulosclerosis regardless of prior treatment. Plasma creatinine and urea were significantly increased in L-NAME treated rats. This study suggests that brief ACE inhibition confers protection against future heart and kidney injury, even in the absence of continued antihypertensive treatment. PMID- 22318206 TI - Effect of a single session of aerobic walking exercise on arterial pressure in community-living elderly individuals. AB - Several studies have demonstrated that one exercise session (ES) on a cycloergometer or ergometric treadmill causes a reduction in blood pressure (BP). However, there are few similar studies on walking, which is the exercise modality most available to the elderly. We investigated the immediate and 24-h effects of walking on BP in independent, community-living elderly individuals. Volunteers participated in a single ES and resting control session (CS). Before and after each session, BP was measured by auscultatory and oscillometric methods. After each session, 24-h ambulatory blood pressure monitoring was conducted. An accelerometer was installed 48 h before the sessions and left in place for 5 days. The mean volunteer age was 67.7+/-3.5 years; 11 were hypertensive patients under treatment, and 12 were normotensive. In the total sample, there were immediate 14mm Hg and 12 mm Hg reductions in systolic BP (SBP) after the ES according to the auscultatory and oscillometric methods, respectively. Diastolic BP (DBP) was reduced by 4 mm Hg after the ES according to both methods. SBP during wakefulness and sleep and DBP during wakefulness were lower after the ES than after the CS (P<0.01), when wakefulness and sleep were determined individually (variable-time pattern) using data from the activity monitors and provided by the volunteers. The variable-time pattern was more effective in detecting reductions in BP than the fixed-time pattern. PMID- 22318207 TI - An observational study to evaluate factors responsible and actions taken for hypertensive patients who are not at blood pressure goal: i-target Goal Study. AB - To evaluate the percentage of hypertensive patients who could achieve target blood pressure (TBP) according to the guidelines in the context of recommended measures and the factors responsible for failure. A total of 589 hypertensive patients (59.0% female; mean age: 57.7 +/- 10.4 years) were assessed twice for TBP achievement based on 2007 ESH/ESC guidelines and the investigators' view, in addition to the recommended measures and possible causes of failure in hypertension management in this national multi-center (n = 99), non interventional observational study. Only 29.5% of the patients at the first visit and 46.8% at the second visit achieved the TBP levels specified by the guidelines. However, the investigators' evaluation indicated a higher achievement rate at the first (43.5%) as well as the second (69.1%) visit when compared with the guideline-based assessments (P < 0.001). The primary reasons identified by the investigators for the failure to reach TBP were non-compliance with dietary recommendations (61.6%) at the first visit and non-compliance with treatment (63.92%) at the second visit. Recommendations for lifestyle were the most commonly identified treatment plan by the investigators at both visits (62.9% and 66.1%, respectively). Although more patients achieved the TBP levels specified by the guidelines for the second visit compared with the first, effective blood pressure control was achieved only in 29.5% of our patients. Interestingly, the investigators had a more optimistic view about their patients' control of hypertension, which may have contributed to a poor achievement of TBP. PMID- 22318208 TI - Veterans service organization engagement in 'POWER,' a peer-led hypertension intervention. AB - OBJECTIVES: The purpose of this study was to determine the influence of program factors on participant engagement in POWER, a peer-led intervention designed to reduce hypertension, increase hypertension knowledge, and improve other relevant health behaviors, such as diet and exercise, among US veterans involved in veterans service organizations throughout Southeastern Wisconsin. METHODS: Two hundred and nineteen hypertensive members from 58 VSOs participated in a year long peer-led intervention designed to improve hypertension knowledge, disease self-management behaviors, and health outcomes. This study represents a qualitative evaluation of post and participant engagement in this intervention. We triangulated data collected via three qualitative approaches (observations, focus groups, and in-depth interviews) from intervention posts to derive a model of engagement. RESULTS: Our findings indicate that discrete characteristics of the peer leaders, post members, posts, and the intervention itself contributed to intervention engagement. DISCUSSION: We make suggestions for future research studies, particularly as related to understanding how peer leader identities and cultural norms within VSOs might contribute to peer-led health intervention success. PMID- 22318209 TI - Peripheral neuropathies in Sjogren's syndrome: a critical update on clinical features and pathogenetic mechanisms. AB - Sjogren's syndrome is a systemic autoimmune disease that, apart from exocrine glands, may affect every organ or system. Involvement of different sections of the peripheral nervous system results in a wide spectrum of neuropathic manifestations. Based on distinct clinical, electrophysiological and histological criteria, the types of neuropathies seen in Sjogren's syndrome include: a) pure sensory which presents with distal symmetric sensory loss due to axonal degeneration of sensory fibers; sensory ataxia due to loss of proprioceptive large fibers (ganglionopathy); or with painful dysethesias (small fiber sensory neuropathy) due to degeneration of cutaneous axons. The latter appears to be the most common neuropathy in Sjogren's syndrome and requires skin biopsy for diagnosis to document loss or reduction of nerve fiber density; b) sensorimotor polyneuropathy affecting sensory and motor axons, often associated with severe systemic or pro-lymhomatous manifestations, such as palpable purpura and cryoglobulinemia, and c) rare types that include autoimmune demyelinating neuropathy, mononeuropathy, mononeuropathy multiplex and autonomic neuropathy. In this review, the frequency, prevalence and diagnostic criteria for each neuropathy subset are discussed and possible pathogenetic mechanisms are outlined. PMID- 22318210 TI - [Spontaneous Achilles tendon rupture as early manifestation of systemic lupus erythematosus]. AB - Spontaneous tendon rupture is rare in the course of systemic lupus erythematosus (SLE). Its incidence rate remains unknown. The pathogenesis of this manifestation is complex and poorly understood. We report a 39-year-old woman who presented with a spontaneous Achilles tendon rupture as the presenting presentation of SLE, before any corticosteroid therapy. All the patients previously published were receiving corticosteroids and reported in some an associated traumatism. Risk factors are prolonged disease duration, chronic therapy with corticosteroids, deforming arthropathy of the hands, and inactive disease. PMID- 22318211 TI - [Enteric nervous system and Parkinson's disease]. AB - It has become increasingly evident over the last years that Parkinson's disease is a multicentric neurodegenerative disease that affects several neuronal structures outside the substantia nigra, among which is the enteric nervous system. The aims of the present article are to discuss the role of the enteric nervous system lesions in pathology spreading (Braak's hypothesis) and in the gastrointestinal dysfunction encountered in Parkinson's disease. Owing to its accessibility to biopsies, we further discuss the use of the enteric nervous system as an original source of biomarker in Parkinson's disease. PMID- 22318212 TI - Word-finding intervention for children with specific language impairment: a multiple single-case study. AB - PURPOSE: This study examined the effectiveness of a combined phonological and semantic intervention for children with specific language impairment who had word finding difficulties (WFDs). METHOD: To evaluate the intervention, a multiple single-case design was implemented with 4 children, ages 9;6 (years;months) to 13;9, who had WFDs. Some items were trained using a phonological intervention; others were trained using a semantic one. Lexical access outcomes were measured using a picture-naming test at pre- and posttesting. RESULTS: Three children exhibited a significant reduction in WFDs on the intervention words after 6 sessions. These effects were present at posttest and 6 months later for the treated words only and not the control words. Each child responded differently to the intervention, and these response patterns seemed to be related to each child's linguistic profile. CONCLUSION: This intervention seemed to achieve long lasting reductions in children's WFDs. The differential responses to phonological and semantic intervention imply the need to tailor intervention for differing children by matching it to their linguistic profile. PMID- 22318214 TI - In situ Raman spectroscopy of surfaces modified by ion soft landing. AB - The design and characterization of a system for in situ Raman analysis of surfaces prepared by ion soft landing (SL) is described. The performance of the new high vacuum compatible, low cost, surface analysis capability is demonstrated with surface enhanced Raman spectroscopy (SERS) of surfaces prepared by soft landing of ions of crystal violet, Rhodamine 6G, methyl orange and copper phthalocyanine. Complementary in situ mass spectrometric information is recorded for the same surfaces using a previously implemented secondary ion mass spectrometer (SIMS). Imaging of the modified surfaces is achieved using 2D Raman imaging as demonstrated for the case of Rhodamine 6G soft landing. The combination of the powerful molecular characterization tools of SERS and SIMS in a single instrument fitted with in-vacuum sample transport capabilities, facilitates in situ analysis of surfaces prepared by ion SL. In particular, information is provided on the charge state of the soft landed species. In the case of crystal violet the SERS data suggest that the positively charged ions being landed retain their charge state on the surface under vacuum. By contrast, in the case of methyl orange which is landed as an anion, the SERS spectra suggest that the SL species has been neutralized. PMID- 22318215 TI - Should complex mitral valve repair be routinely performed using a minimally invasive approach? AB - PURPOSE OF REVIEW: To review selected recent publications on minimally invasive mitral valve surgery to help answer the question as to whether the minimally invasive approach should be routinely used in complex mitral valve repairs. RECENT FINDINGS: Other than cosmesis, there have not been demonstrable reproducible benefits of the minimally invasive approach. Although some workers report excellent results, there are other data that raise concern that complex repairs are less likely to be undertaken via the minimal access approach, resulting in lower repair rates, and also that the incidence of residual regurgitation may be higher. Some complications, such as stroke, may occur with greater frequency in patients having the minimally invasive approach. SUMMARY: The minimally invasive approach for complex mitral valve repair requires continued development and investigation, and current application should probably be largely restricted to high-volume reference minimally invasive surgery centers. PMID- 22318216 TI - New sutureless aortic valve prosthesis: another tool in less invasive aortic valve replacement. AB - PURPOSE OF REVIEW: Sutureless aortic valve prosthesis is a new and promising tool for treatment of aortic valve stenosis. It could increase applicability of surgical aortic valve replacement in the elderly with severe comorbidities. RECENT FINDINGS: Three devices are currently available. The 3f Enable (ATS, Minneapolis, USA) and the Perceval S (Sorin, Saluggia, Italy) have a CE mark, whereas the Intuity (Edwards Lifesciences, Irvine, California) is still under investigation. We present the above valves, focusing on the Perceval S, which was used in our institution. Indications, contraindications, technical considerations and patient selection are described. The potential advantages of sutureless valve technology over conventional aortic and percutaneous valves are discussed. We emphasize new perspectives offered by sutureless valves in the aortic replacement field. SUMMARY: This new technology may offer improved results. Cost effectiveness and fine-tuning of patient selection are two aspects that future investigation should address. PMID- 22318217 TI - Heart failure with normal left ventricular ejection fraction: role of echocardiography. AB - PURPOSE OF REVIEW: Nearly half of patients presenting with heart failure have a preserved left ventricular ejection fraction (LVEF), previously known as diastolic heart failure. The diagnosis requires fulfillment of three criteria: signs or symptoms of heart failure, presence of a normal LVEF, and evidence of diastolic dysfunction. Two of the criteria can be evaluated by echocardiography. This article reviews the echocardiographic approach to the patient with suspected heart failure with a normal left ventricular ejection fraction (HFNEF). RECENT FINDINGS: Echocardiography is the primary modality for evaluating left ventricular (LV) systolic and diastolic function in heart failure patients. Measurements of LVEF from two-dimensional echocardiography can have significant variability despite the use of quantitative methods. The use of contrast agents and three-dimensional echocardiography can improve the accuracy. Newer modalities of tissue Doppler imaging and deformation imaging are challenging the concept that systolic function is preserved in HFNEF. Evaluation of diastolic function with echocardiography requires a comprehensive approach using multiple modalities to quantitate transmitral flow, pulmonary venous flow, mitral annular motion, myocardial deformation, and cardiac structure. The clinical applicability of parameters used for evaluating diastolic function and filling pressures is dependent on the LVEF, necessitating a unique approach in patients with suspected HFNEF. SUMMARY: A comprehensive examination with knowledge of the potential limitations of echocardiography is required to accurately interpret LV systolic and diastolic function in patients with suspected HFNEF. PMID- 22318218 TI - The treatment of venous thromboembolism with low-molecular-weight heparins. A meta-analysis. AB - The currently recommended method of venous thromboembolism (VTE) treatment is the application of vitamin K antagonists (VKA) in most patients, and low-molecular weight heparins (LMWH) in selected groups. The VKA dose adjustment is difficult which might well render the treatment ineffective. The study aimed to compare LMWH with VKA in treating VTE in terms of efficacy and safety. A systematic review of literature and the meta-analysis of the treatment results were performed. The main differences between LMWH and VKA in terms of their respective effectiveness in treating VTE consist in appreciably more advantageous effects of LMWH in preventing deep venous thrombosis (DVT). The key difference in terms of respective safety is the greater effectiveness of LMWH inpreventing minor bleedings. The advantage of LMWH in cancer patients consists predominantly in a significantly better protection against DVT episodes, whereas the advantage of LMWH in non-cancer patients is mainly owed to better protection against minor bleedings. In none of the analysed outcomes of VTE treatment, the application of VKA proved to hold any advantage over LMWH. Although, arguably, there might well be sufficient medical grounds to propose more widespread use of LMWH, it still remains a debatable issue whether the currently used therapeutic standard should also be modified accordingly. Apart from the actual findings of the present meta analysis, pertinent economic considerations must also be addressed. PMID- 22318219 TI - Determinants of low-density lipoprotein particle diameter during antiretroviral therapy including protease inhibitors in HIV-1-infected patients. AB - BACKGROUND: Lipid disorders are frequent in HIV-1-infected patients taking combination antiretroviral therapy (cART) that includes protease inhibitors (PIs). The presence of small dense low-density lipoprotein particles might be an important predictive marker of cardiovascular disease in this setting. This cross sectional substudy of the ANRS 126 trial was designed to identify variables influencing LDL diameter. METHODS: We studied 81 stable HIV-1-infected patients with dyslipidaemia (LDL-cholesterol >4.1 mmol/l, triglycerides <8.8 mmol/l) receiving PI-including cART regimens and no lipid-lowering drugs. LDL diameter was assessed by gradient gel electrophoresis. Relationships between LDL diameter and demographic, metabolic and HIV-related variables were identified by using non parametric univariate tests and multiple linear regression models. RESULTS: In univariate analysis, LDL diameter was related to demographic variables, triglyceride (TG) levels, high-density lipoprotein cholesterol (HDL-c) levels, and the numbers and duration of exposure to nucleoside reverse transcriptase inhibitors and PIs. In multivariable linear regression analysis, LDL diameter was negatively associated with the TG level (P<0.0001) and positively associated with the HDL-c level (P<0.0001). For each 1-mmol/l increase in TG, LDL diameter fell by 0.281 nm. Conversely, for each 1-mmol/l increase in HDL-c, LDL diameter rose by 1.175 nm. CONCLUSIONS: Higher TG and lower HDL-c levels are associated with smaller LDL particle diameter. Small-diameter LDL particles could contribute to early atherogenic processes in HIV-1-infected patients on cART. PMID- 22318220 TI - Variation in water potential, hydraulic characteristics and water source use in montane Douglas-fir and lodgepole pine trees in southwestern Alberta and consequences for seasonal changes in photosynthetic capacity. AB - Tree species response to climate change-induced shifts in the hydrological cycle depends on many physiological traits, particularly variation in water relations characteristics. We evaluated differences in shoot water potential, vulnerability of branches to reductions in hydraulic conductivity, and water source use between Pinus contorta Dougl. ex Loud. var. latifolia Engelm. (lodgepole pine) and Pseudotsuga menziesii (Mirb.) Franco (interior Douglas-fir), and determined the consequences for seasonal changes in photosynthetic capacity. The Douglas-fir site had soil with greater depth, finer texture and higher organic matter content than soil at the lodgepole pine site, all factors that increased the storage of soil moisture. While the measured xylem vulnerability curves were quite similar for the two species, Douglas-fir had lower average midday shoot water potentials than did lodgepole pine. This implied that lodgepole pine exhibited stronger stomatal control of transpiration than Douglas-fir, which helped to reduce the magnitude of the water potential gradient required to access water from drying soil. Stable hydrogen isotope measurements indicated that Douglas-fir increased the use of groundwater during mid-summer when precipitation inputs were low, while lodgepole pine did not. There was a greater reduction of photosynthetic carbon gain in lodgepole pine compared with Douglas-fir when the two tree species were exposed to seasonal declines in soil water content. The contrasting patterns of seasonal variation in photosynthetic capacity observed for the two species were a combined result of differences in soil characteristics at the separate sites and the inherent physiological differences between the species. PMID- 22318221 TI - The Latarjet procedure: the patient population makes all the difference: commentary on an article by Anup A. Shah, MD, et al.: "Short-term complications of the Latarjet procedure". PMID- 22318222 TI - Short-term complications of the Latarjet procedure. AB - BACKGROUND: Although the results of the Latarjet procedure have been reported previously, there is little literature regarding the early complications of this procedure. The purpose of this study was to report our experience with the Latarjet procedure for glenohumeral instability and to highlight the initial complications that may occur following this procedure. METHODS: Forty-seven patients (forty-eight shoulders) underwent the Latarjet procedure for anterior glenohumeral instability between January 2005 and January 2010. All shoulders had some osseous deficiency of the anterior glenoid rim or had undergone an unsuccessful prior soft-tissue Bankart repair. The minimum duration of patient follow-up was six months. RESULTS: Forty-five shoulders were available for follow up. The overall complication rate was 25% (twelve of the original forty-eight shoulders). Complications were divided into three groups: infection, recurrent glenohumeral instability, and neurologic injury. A superficial infection developed in three shoulders (6%); in all cases, the infection resolved following irrigation and debridement and administration of antibiotics for up to four weeks. Four shoulders (8%) developed recurrent glenohumeral instability; this occurred within eight months in two shoulders and at nineteen and forty-two months postoperatively in the other two. Five procedures (10%) resulted in a neurologic injury. Two of these involved the musculocutaneous nerve, one involved the radial nerve, and two involved the axillary nerve. The three musculocutaneous and radial nerve injuries involved sensory neurapraxia that resolved fully within two months. Both of the patients with axillary nerve dysfunction continued to have persistent sensory disturbances and one continued to have residual weakness that had not yet resolved fully at the time of the final follow-up. CONCLUSIONS: The overall complication rate of 25% is higher than that reported in the literature. Although most of these complications resolved completely, two patients continued to have residual neurologic symptoms. Patients should be informed of the risk of complications associated with the Latarjet procedure, although most of the potential complications will resolve. PMID- 22318223 TI - Recognizing and preventing acute stroke in women. PMID- 22318225 TI - An essential role for a mammalian SWI/SNF chromatin-remodeling complex during male meiosis. AB - Germ cell development and gametogenesis require genome-wide transitions in epigenetic modifications and chromatin structure. These changes include covalent modifications to the DNA and histones as well as remodeling activities. Here, we explore the role of the mammalian SWI/SNF chromatin-remodeling complex during spermatogenesis using a conditional allele of the ATPase subunit, brahma-related gene 1 (Brg1, or Smarca4). Not only do BRG1 levels peak during the early stages of meiosis, genetic ablation of Brg1 in murine embryonic gonocytes results in arrest during prophase of meiosis I. Coincident with the timing of meiotic arrest, mutant spermatocytes accumulate unrepaired DNA and fail to complete synapsis. Furthermore, mutant spermatocytes show global alterations to histone modifications and chromatin structure indicative of a more heterochromatic genome. Together, these data demonstrate a requirement for BRG1 activity in spermatogenesis, and suggest a role for the mammalian SWI/SNF complex in programmed recombination and repair events that take place during meiosis. PMID- 22318224 TI - PRMT5 and the role of symmetrical dimethylarginine in chromatoid bodies of planarian stem cells. AB - Planarian flatworms contain a population of adult stem cells (neoblasts) that proliferate and generate cells of all tissues during growth, regeneration and tissue homeostasis. A characteristic feature of neoblasts is the presence of chromatoid bodies, large cytoplasmic ribonucleoprotein (RNP) granules morphologically similar to structures present in the germline of many organisms. This study aims to reveal the function, and identify additional components, of planarian chromatoid bodies. We uncover the presence of symmetrical dimethylarginine (sDMA) on chromatoid body components and identify the ortholog of protein arginine methyltransferase PRMT5 as the enzyme responsible for sDMA modification in these proteins. RNA interference-mediated depletion of planarian PRMT5 results in defects in homeostasis and regeneration, reduced animal size, reduced number of neoblasts, fewer chromatoid bodies and increased levels of transposon and repetitive-element transcripts. Our results suggest that PIWI family member SMEDWI-3 is one sDMA-containing chromatoid body protein for which methylation depends on PRMT5. Additionally, we discover an RNA localized to chromatoid bodies, germinal histone H4. Our results reveal new components of chromatoid bodies and their function in planarian stem cells, and also support emerging studies indicative of sDMA function in stabilization of RNP granules and the Piwi-interacting RNA pathway. PMID- 22318226 TI - The cyclophilin DIAGEOTROPICA has a conserved role in auxin signaling. AB - Auxin has a fundamental role throughout the life cycle of land plants. Previous studies showed that the tomato cyclophilin DIAGEOTROPICA (DGT) promotes auxin response, but its specific role in auxin signaling remains unknown. We sequenced candidate genes in auxin-insensitive mutants of Physcomitrella patens and identified mutations in highly conserved regions of the moss ortholog of tomato DGT. As P. patens and tomato diverged from a common ancestor more than 500 million years ago, this result suggests a conserved and central role for DGT in auxin signaling in land plants. In this study we characterize the P. patens dgt (Ppdgt) mutants and show that their response to auxin is altered, affecting the chloronema-to-caulonema transition and the development of rhizoids. To gain an understanding of PpDGT function we tested its interactions with the TIR1/AFB dependent auxin signaling pathway. We did not observe a clear effect of the Ppdgt mutation on the degradation of Aux/IAA proteins. However, the induction of several auxin-regulated genes was reduced. Genetic analysis revealed that dgt can suppress the phenotype conferred by overexpression of an AFB auxin receptor. Our results indicate that the DGT protein affects auxin-induced transcription and has a conserved function in auxin regulation in land plants. PMID- 22318227 TI - Morphogen-based simulation model of ray growth and joint patterning during fin development and regeneration. AB - The fact that some organisms are able to regenerate organs of the correct shape and size following amputation is particularly fascinating, but the mechanism by which this occurs remains poorly understood. The zebrafish (Danio rerio) caudal fin has emerged as a model system for the study of bone development and regeneration. The fin comprises 16 to 18 bony rays, each containing multiple joints along its proximodistal axis that give rise to segments. Experimental observations on fin ray growth, regeneration and joint formation have been described, but no unified theory has yet been put forward to explain how growth and joint patterns are controlled. We present a model for the control of fin ray growth during development and regeneration, integrated with a model for joint pattern formation, which is in agreement with published, as well as new, experimental data. We propose that fin ray growth and joint patterning are coordinated through the interaction of three morphogens. When the model is extended to incorporate multiple rays across the fin, it also accounts for how the caudal fin acquires its shape during development, and regains its correct size and shape following amputation. PMID- 22318228 TI - SIK3 is essential for chondrocyte hypertrophy during skeletal development in mice. AB - Chondrocyte hypertrophy is crucial for endochondral ossification, but the mechanism underlying this process is not fully understood. We report that salt inducible kinase 3 (SIK3) deficiency causes severe inhibition of chondrocyte hypertrophy in mice. SIK3-deficient mice showed dwarfism as they aged, whereas body size was unaffected during embryogenesis. Anatomical and histological analyses revealed marked expansion of the growth plate and articular cartilage regions in the limbs, accumulation of chondrocytes in the sternum, ribs and spine, and impaired skull bone formation in SIK3-deficient mice. The primary phenotype in the skeletal tissue of SIK3-deficient mice was in the humerus at E14.5, where chondrocyte hypertrophy was markedly delayed. Chondrocyte hypertrophy was severely blocked until E18.5, and the proliferative chondrocytes occupied the inside of the humerus. Consistent with impaired chondrocyte hypertrophy in SIK3-deficient mice, native SIK3 expression was detected in the cytoplasm of prehypertrophic and hypertrophic chondrocytes in developing bones in embryos and in the growth plates in postnatal mice. HDAC4, a crucial repressor of chondrocyte hypertrophy, remained in the nuclei in SIK3-deficient chondrocytes, but was localized in the cytoplasm in wild-type hypertrophic chondrocytes. Molecular and cellular analyses demonstrated that SIK3 was required for anchoring HDAC4 in the cytoplasm, thereby releasing MEF2C, a crucial facilitator of chondrocyte hypertrophy, from suppression by HDAC4 in nuclei. Chondrocyte specific overexpression of SIK3 induced closure of growth plates in adulthood, and the SIK3-deficient cartilage phenotype was rescued by transgenic SIK3 expression in the humerus. These results demonstrate an essential role for SIK3 in facilitating chondrocyte hypertrophy during skeletogenesis and growth plate maintenance. PMID- 22318229 TI - Mirror represses pipe expression in follicle cells to initiate dorsoventral axis formation in Drosophila. AB - Dorsoventral (DV) axis formation in Drosophila begins with selective activation of EGFR, a receptor tyrosine kinase (RTK), in dorsal-anterior (DA) ovarian follicle cells. A critical event regulated by EGFR signaling is the repression of the sulfotransferase-encoding gene pipe in dorsal follicle cells, but how this occurs remains unclear. Here we show that Mirror (Mirr), a homeodomain transcription factor induced by EGFR signaling in DA follicle cells, directly represses pipe expression by binding to a conserved element in the pipe regulatory region. In addition, we find that the HMG-box protein Capicua (Cic) supports pipe expression in ventral follicle cells by repressing Mirr in this region. Interestingly, this role of Cic resembles its function in regulating anteroposterior (AP) body patterning, where Cic supports gap gene expression in central regions of the embryo by repressing Tailless, a repressor induced by RTK signaling at the embryonic poles. Thus, related RTK-Cic repressor circuits regulate the early stages of Drosophila DV and AP body axis formation. PMID- 22318230 TI - The CDC25B phosphatase shortens the G2 phase of neural progenitors and promotes efficient neuron production. AB - During embryonic development, changes in cell cycle kinetics have been associated with neurogenesis. This observation suggests that specific cell cycle regulators may be recruited to modify cell cycle dynamics and influence the decision between proliferation and differentiation. In the present study, we investigate the role of core positive cell cycle regulators, the CDC25 phosphatases, in this process. We report that, in the developing chicken spinal cord, only CDC25A is expressed in domains where neural progenitors undergo proliferative self-renewing divisions, whereas the combinatorial expression of CDC25A and CDC25B correlates remarkably well with areas where neurogenesis occurs. We also establish that neural progenitors expressing both CDC25A and CDC25B have a shorter G2 phase than those expressing CDC25A alone. We examine the functional relevance of these correlations using an RNAi-based method that allows us to knock down CDC25B efficiently and specifically. Reducing CDC25B expression results in a specific lengthening of the G2 phase, whereas the S-phase length and the total cell cycle time are not significantly modified. This modification of cell cycle kinetics is associated with a reduction in neuron production that is due to the altered conversion of proliferating neural progenitor cells to post-mitotic neurons. Thus, expression of CDC25B in neural progenitors has two functions: to change cell cycle kinetics and in particular G2-phase length and also to promote neuron production, identifying new roles for this phosphatase during neurogenesis. PMID- 22318231 TI - Differential distribution of competence for panplacodal and neural crest induction to non-neural and neural ectoderm. AB - It is still controversial whether cranial placodes and neural crest cells arise from a common precursor at the neural plate border or whether placodes arise from non-neural ectoderm and neural crest from neural ectoderm. Using tissue grafting in embryos of Xenopus laevis, we show here that the competence for induction of neural plate, neural plate border and neural crest markers is confined to neural ectoderm, whereas competence for induction of panplacodal markers is confined to non-neural ectoderm. This differential distribution of competence is established during gastrulation paralleling the dorsal restriction of neural competence. We further show that Dlx3 and GATA2 are required cell-autonomously for panplacodal and epidermal marker expression in the non-neural ectoderm, while ectopic expression of Dlx3 or GATA2 in the neural plate suppresses neural plate, border and crest markers. Overexpression of Dlx3 (but not GATA2) in the neural plate is sufficient to induce different non-neural markers in a signaling-dependent manner, with epidermal markers being induced in the presence, and panplacodal markers in the absence, of BMP signaling. Taken together, these findings demonstrate a non-neural versus neural origin of placodes and neural crest, respectively, strongly implicate Dlx3 in the regulation of non-neural competence, and show that GATA2 contributes to non-neural competence but is not sufficient to promote it ectopically. PMID- 22318232 TI - The role of Hes genes in intestinal development, homeostasis and tumor formation. AB - Notch signaling regulates intestinal development, homeostasis and tumorigenesis, but its precise downstream mechanism remains largely unknown. Here we found that inactivation of the Notch effectors Hes1, Hes3 and Hes5, but not Hes1 alone, led to reduced cell proliferation, increased secretory cell formation and altered intestinal structures in adult mice. However, in Apc mutation-induced intestinal tumors, inactivation of Hes1 alone was sufficient for reducing tumor cell proliferation and inducing differentiation of tumor cells into all types of intestinal epithelial cells, but without affecting the homeostasis of normal crypts owing to genetic redundancy. These results indicated that Hes genes cooperatively regulate intestinal development and homeostasis and raised the possibility that Hes1 is a promising target to induce the differentiation of tumor cells. PMID- 22318233 TI - Role of motoneuron-derived neurotrophin 3 in survival and axonal projection of sensory neurons during neural circuit formation. AB - Sensory neurons possess the central and peripheral branches and they form unique spinal neural circuits with motoneurons during development. Peripheral branches of sensory axons fasciculate with the motor axons that extend toward the peripheral muscles from the central nervous system (CNS), whereas the central branches of proprioceptive sensory neurons directly innervate motoneurons. Although anatomically well documented, the molecular mechanism underlying sensory motor interaction during neural circuit formation is not fully understood. To investigate the role of motoneuron on sensory neuron development, we analyzed sensory neuron phenotypes in the dorsal root ganglia (DRG) of Olig2 knockout (KO) mouse embryos, which lack motoneurons. We found an increased number of apoptotic cells in the DRG of Olig2 KO embryos at embryonic day (E) 10.5. Furthermore, abnormal axonal projections of sensory neurons were observed in both the peripheral branches at E10.5 and central branches at E15.5. To understand the motoneuron-derived factor that regulates sensory neuron development, we focused on neurotrophin 3 (Ntf3; NT-3), because Ntf3 and its receptors (Trk) are strongly expressed in motoneurons and sensory neurons, respectively. The significance of motoneuron-derived Ntf3 was analyzed using Ntf3 conditional knockout (cKO) embryos, in which we observed increased apoptosis and abnormal projection of the central branch innervating motoneuron, the phenotypes being apparently comparable with that of Olig2 KO embryos. Taken together, we show that the motoneuron is a functional source of Ntf3 and motoneuron-derived Ntf3 is an essential pre-target neurotrophin for survival and axonal projection of sensory neurons. PMID- 22318235 TI - RB: mitotic implications of a tumour suppressor. AB - RB, a well known tumour suppressor that functions in the control of cell cycle progression and proliferation, has recently been shown to have additional functions in the maintenance of genomic stability, such that inactivation of RB family proteins promotes chromosome instability (CIN) and aneuploidy. Several studies have provided potential explanations for these phenomena that occur following RB loss, and they suggest that this new function of RB may contribute to its role in tumour suppression. PMID- 22318236 TI - Navigating uncharted territory. PMID- 22318238 TI - Hybridization chain reaction-based aptameric system for the highly selective and sensitive detection of protein. AB - We introduce here a novel assay for the detection of platelet-derived growth factor BB (PDGF-BB) via hybridization chain reaction (HCR) based on an aptameric system, where stable DNA monomers assemble only upon exposure to a target PDGF-BB aptamer. In this process, two complementary stable species of biotinylated DNA hairpins coexist in solution until the introduction of initiator aptamer strands triggers a cascade of hybridization events that yields nicked double helices analogous to alternating copolymers. In detail, the aptamer firstly opens the hairpins in the solution, creating long concatemers, and then reacts with the antibody captured PDGF-BB on the well surface. Moreover, several experimental conditions including different PDGF-BB aptamers, the spacer length of the selected aptamer and hairpin, etc. are investigated and optimized. Our results show that the coupling of HCR to aptamer triggers for the amplification detection of PDGF-BB achieves a better performance in the fluorescence detection of PDGF-BB as compared to the traditional antibody-antigen-aptamer assays. Upon modification, the approach presented herein could be extended to detect other types of targets. We believe such advancements will represent a significant step towards improved diagnostics and more personalized medical treatment and environmental monitoring. PMID- 22318239 TI - Using residents' perceptions to improve park-people relationships in Chatthin Wildlife Sanctuary, Myanmar. AB - The complex and context-specific relationships that local residents have with neighboring protected areas present many challenges for protected area (PA) management. While long-term, interdisciplinary approaches may be necessary to fully understand park-people relationships within a particular PA, the reality is that management decisions for the majority of PAs in the world are made by protected area staff with little or no external assistance. One potential entry point for management to understand park-people relationships and improve management is through understanding people's perceptions of PAs. This paper presents a study from Chatthin Wildlife Sanctuary in central Myanmar designed to explore the impact of using residents' attitudes to directly inform management strategies. We conducted a survey to determine attitudes and determinants of attitudes toward CWS. In response to the survey, the warden made changes to the Sanctuary's management strategy to accommodate local needs and perceptions. Four years later, we repeated the survey to explore the effects of the management changes on people's perceptions and found that people were significantly more likely to like the sanctuary, less likely to mention problems, and more likely to mention benefits. People's negative perceptions of management conflicts and crop damage decreased and their positive perceptions of conservation and ecosystem service benefits and extraction benefits increased. This study demonstrates that residents' perceptions can be used by management as a starting point to improve park-people relationships through feasible and targeted interventions that are meaningful to local communities and their relationships with PAs. PMID- 22318237 TI - The role of peroxisome proliferator-activated receptors in carcinogenesis and chemoprevention. AB - Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that are involved in regulating glucose and lipid homeostasis, inflammation, proliferation and differentiation. Although all of these functions might contribute to the influence of PPARs in carcinogenesis, there is a distinct need for a review of the literature and additional experimentation to determine the potential for targeting PPARs for cancer therapy and cancer chemoprevention. As PPAR agonists include drugs that are used for the treatment of metabolic diseases, a more complete understanding of the roles of PPARs in cancer will aid in determining any increased cancer risk for patients undergoing therapy with PPAR agonists. PMID- 22318240 TI - Electrocoagulation of commercial naphthalene sulfonates: process optimization and assessment of implementation potential. AB - The commercially important naphthalene sulfonate K-acid (C(10)H(9)NO(9)S(3); 2 naphthylamine 3,6,8-tri sulfonic acid) was subjected to electrocoagulation employing stainless steel electrodes. An experimental design tool was used to mathematically describe and optimize the single and combined influences of major process variables on K-acid and its organic carbon (COD and TOC) removal efficiencies as well as electrical energy consumption. Current density, followed by treatment time were found to be the parameters affecting process responses most significantly, whereas initial K-acid concentration had the least influence on the electrocoagulation performance. Process economics including sludge generation, electrode consumption, and electrochemical efficiency, as well as organically bound adsorbable halogen formation and toxicity evolution were primarily considered to question the feasibility of K-acid electrocoagulation. Considering process economics and ecotoxicological parameters, process implementation appeared to be encouraging. PMID- 22318244 TI - A comparison of data quality control protocols for atmospheric mercury speciation measurements. AB - Significant advances in the measurement of atmospheric mercury species have been made in the past 10 years yet limited protocols on quality control (QC) and assurance on this data have been published in the literature. Recently, considerable work has been done to develop quality control and assurance programs within North America. Environment Canada and the National Atmospheric Deposition Network (NADP) independently developed programs, RDMQTM and AMQC, respectively, to QC atmospheric mercury speciation data (including gaseous elemental mercury (GEM), reactive gaseous mercury (RGM) and mercury associated to particles (PHg)). These 2 programs were assessed by the criteria on which the data is QCed and comparability of the final data products. Results show that the criteria used to flag data compare well within the 4 tested sites and that the number of flags for each criterion is generally comparable. The QC programs were applied to 2 distinct data sets and the final QCed data was compared. From a mid-latitude site, the final data sets compare very well and showed there to be a 0.3, 8.6 and 15% difference in the mean GEM, RGM and PHg concentrations post QC of each program. It is recommended that either the RDMQ or the AMQC programs be employed for a typical mid-latitude site. When the QC programs were applied to highly variable data, the data do not compare as well for RGM and PHg. Results showed a 2.7, 27 and 33% difference in the mean GEM, RGM and PHg concentrations, respectively, post QC of each program. It is recommended that RDMQ be used for data that is highly variable with high RGM/PHg concentrations as it allows for more manual correction over the QCed data. This investigation of 2 QC programs produced comparable data and that either of these programs can be used as standard methods for the quality control of atmospheric mercury speciation data. PMID- 22318246 TI - Effect of everolimus on left ventricular hypertrophy of de novo kidney transplant recipients: a 1 year, randomized, controlled trial. AB - BACKGROUND: Although conversion from calcineurin inhibitors to mammalian target of rapamycin inhibitors proved to be effective in regressing left ventricular hypertrophy (LVH) in renal transplant recipients (RTRs) with chronic allograft dysfunction, there are currently no reports of randomized trials on this issue involving de novo RTRs administered everolimus (EVL). METHODS: This randomized, open-label, controlled trial evaluated the effect of EVL on the left ventricular mass index (LVMi) of 30 nondiabetic RTRs (21 men; age 28-65 years). Ten were allocated to EVL plus reduced-exposure cyclosporine A (CsA), and 20 to standard dose CsA. LVMi was assessed by echocardiography both at baseline and 1 year later. Blood pressure (BP), hemoglobin, serum creatinine, lipids, trough levels of immunosuppressive drugs, and daily proteinuria were also evaluated twice monthly. Antihypertensive therapy that did not include renin-angiotensin system blockers was administered to achieve BP less than or equal to 130/80 mm Hg. RESULTS: Changes in BP were similar in the two groups (between group difference 1.2 +/- 5.7 mm Hg, P=0.84 for systolic, and -1.5 +/- 3.7, P=0.69, for diastolic BP), whereas LVMi significantly decreased in the EVL group alone (between group difference 9.2 +/- 3.1 g/m(2.7), P=0.005), due to a reduction in both the interventricular septum and the left ventricular posterior wall thickness. EVL therapy together with baseline LVMi were the only significant predictors of LVH regression according to a multivariate model that explained 49% of the total LVMi variance (P=0.0015). CONCLUSIONS: An immunosuppressive regimen consisting of EVL plus reduced exposure CsA proved to be effective in regressing LVH in RTRs regardless of BP, mainly by reducing left ventricular wall thickness. PMID- 22318245 TI - A new enzyme mixture to increase the yield and transplant rate of autologous and allogeneic human islet products. AB - BACKGROUND: The optimal enzyme blend that maximizes human islet yield for transplantation remains to be determined. In this study, we evaluated eight different enzyme combinations (ECs) in an attempt to improve islet yield. The ECs consisted of purified, intact or truncated class 1 (C1) and class 2 (C2) collagenases from Clostridium histolyticum (Ch), and neutral protease (NP) from Bacillus thermoproteolyticus rokko (thermolysin) or Ch (ChNP). METHODS: We report the results of 249 human islet isolations, including 99 deceased donors (research n=57, clinical n=42) and 150 chronic pancreatitis pancreases. We prepared a new enzyme mixture (NEM) composed of intact C1 and C2 collagenases and ChNP in place of thermolysin. The NEM was first tested in split pancreas (n=5) experiments and then used for islet autologous (n=21) and allogeneic transplantation (n=10). Islet isolation outcomes from eight different ECs were statistically compared using multivariate analysis. RESULTS: The NEM consistently achieved higher islet yields from pancreatitis (P<0.003) and deceased donor pancreases (P<0.001) than other standard ECs. Using the NEM, islet products met release criteria for transplantation from 8 of 10 consecutive pancreases, averaging 6510 +/- 2150 islet equivalent number/gram (IEQ/g) pancreas and 694,681 +/- 147,356 total IEQ/transplantation. In autologous isolation, the NEM yielded more than 200,000 IEQ from 19 of 21 pancreases (averaging 422,893 +/- 181,329 total IEQ and 5979 +/ 1469 IEQ/kg recipient body weight) regardless of the severity of fibrosis. CONCLUSIONS: A NEM composed of ChNP with CIzyme high intact C1 collagenase recovers higher islet yield from deceased and pancreatitis pancreases while retaining islet quality and function. PMID- 22318247 TI - Altered plantar-receptor stimulation impairs postural control in those with chronic ankle instability. AB - CONTEXT: Postural control as assessed via time-to-boundary (TTB) measures has been shown to be impaired in those with chronic ankle instability (CAI). Foot orthotics have been shown to improve postural control, although it is not clear if this is via mechanical or sensorimotor mechanisms. OBJECTIVE: To assess the effect of textured shoe inserts that provide no mechanical support on postural control as assessed by TTB measures in subjects with CAI. DESIGN: A crossover design to examine the effects of a textured insole on postural control in individuals with unilateral CAI. The independent variables were vision (eyes open, eyes closed) and texture (textured insole, sham insole, control). SETTING: Laboratory. PARTICIPANTS: 20 physically active individuals, 12 men, 8 women, age 18-45 y (21.5 +/- 5.51) with self-reported CAI. INTERVENTION: Each subject balanced in shod single-limb stance with eyes open and eyes closed under 3 conditions (control, sham, and textured insole). The order of testing under the 3 shoe conditions and 2 vision conditions was counterbalanced. MAIN OUTCOME MEASURES: The mean of TTB minima and the standard deviation of TTB minima in the mediolateral (ML) and anteroposterior directions. RESULTS: There were significant reductions in TTB ML magnitude and variability found in the textured condition compared with the control and sham conditions. In the textured condition, subjects failed significantly more trials than any other condition. CONCLUSIONS: Stimulating the plantar surface of the foot, via a textured insole, has an effect in the broad spectrum of postural-control maintenance in individuals with CAI. PMID- 22318257 TI - Telocytes in the interstitium of human exocrine pancreas: ultrastructural evidence. AB - OBJECTIVES: Pancreatic interstitial cells are located among acini, ducts, nerves, and blood vessels. They are essential for pancreas development, physiology, and for oncogenic microenvironment. We identified cells with characteristic ultrastructural features of telocytes in pancreatic interstitium. Telocytes were initially described as interstitial Cajal-like cells, but it gradually became clear that they were a distinct novel cell type not directly related to canonical interstitial Cajal cells. METHODS: Serial ultrathin sections of human pancreatic tissue were studied by transmission electron microscopy. Computer analysis software was used to obtain 2-dimensional compositions from serial micrographs and to perform morphometry. RESULTS: Pancreatic telocytes appear as small-body cells with prolongations called telopodes. The ultrastructural features of telopodes are the following: (a) number: 1 to 3; (b) length: tens of micrometers; (c) moniliform aspect: with podoms (thicker portions) and podomers (thin segments, with a mean width of 60 nm, undetectable by light microscopy); (d) dichotomous branching forming a network; (e) establish homocellular and heterocellular junctions; (f) release of microvesicles/multivesicular bodies. Telopodes pass close to blood vessels, nerves, and pancreatic acinar cells and ducts. CONCLUSIONS: Telocytes are present as distinct interstitial cells in the exocrine pancreatic stroma. They act as important players in intercellular signaling via stromal synapses and shed vesicle transfer. PMID- 22318258 TI - X-ray fluorescence holography. AB - X-ray fluorescence holography (XFH) is a method of atomic resolution holography which utilizes fluorescing atoms as a wave source or a monitor of the interference field within a crystal sample. It provides three-dimensional atomic images around a specified element and has a range of up to a few nm in real space. Because of this feature, XFH is expected to be used for medium-range local structural analysis, which cannot be performed by x-ray diffraction or x-ray absorption fine structure analysis. In this article, we explain the theory of XFH including solutions to the twin-image problem, an advanced measuring system, and data processing for the reconstruction of atomic images. Then, we briefly introduce our recent applications of this technique to the analysis of local lattice distortions in mixed crystals and nanometer-size clusters appearing in the low-temperature phase of a shape-memory alloy. PMID- 22318259 TI - Lessons learned. PMID- 22318260 TI - The HDE: what is it good for? Absolutely nothing? PMID- 22318261 TI - Introduction to point-counterpoint. PMID- 22318262 TI - Medical treatment of intracranial atherosclerosis has been shown to be superior. PMID- 22318263 TI - Intracranial stenting for intracranial atherosclerotic disease: still much to learn. PMID- 22318265 TI - Re: Perez et al 'Intracranial thrombectomy using the Solitaire stent: a historical vignette'. PMID- 22318267 TI - The cover. Dynamism of a human body. PMID- 22318268 TI - NIH program helps developers navigate path to new drugs for neglected diseases. PMID- 22318269 TI - Heart disease and stroke deaths fall, but some fear a reverse in the trend. PMID- 22318270 TI - Physicians' offices play key role in promoting vaccination to adult patients. PMID- 22318271 TI - Cognitive behavior therapy for pediatric obsessive-compulsive disorder. PMID- 22318272 TI - Differences in an author's conflict of interest disclosures. PMID- 22318273 TI - Levels of plasma trans-fatty acids in non-Hispanic white adults in the United States in 2000 and 2009. PMID- 22318274 TI - The harms of screening: new attention to an old concern. PMID- 22318275 TI - Nocebo effects, patient-clinician communication, and therapeutic outcomes. PMID- 22318276 TI - Integrating technology into health care: what will it take? PMID- 22318277 TI - A piece of my mind. What would Patsy Mink think? PMID- 22318278 TI - Immunogenicity and tolerability of recombinant serogroup B meningococcal vaccine administered with or without routine infant vaccinations according to different immunization schedules: a randomized controlled trial. AB - CONTEXT: In the absence of an effective vaccine, serogroup B Neisseria meningitidis (MenB) remains a major cause of invasive disease in early childhood in developed countries. OBJECTIVE: To determine the immunogenicity and reactogenicity of a multicomponent MenB vaccine (4CMenB) and routine infant vaccines when given either concomitantly or separately. DESIGN, SETTING, AND PARTICIPANTS: Phase 2b, multicenter, open-label, parallel-group, randomized controlled study of 1885 infants enrolled at age 2 months from August 2008 to July 2010 in Europe. INTERVENTION: Participants were randomized 2:2:1:1 to receive (1) 4CMenB at 2, 4, and 6 months with routine vaccines (7-valent pneumococcal and combined diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B, Haemophilus influenzae type b vaccines); (2) 4CMenB at 2, 4, and 6 months and routine vaccines at 3, 5, and 7 months; (3) 4CMenB with routine vaccines at 2, 3, and 4 months; or (4) routine vaccines alone at 2, 3, and 4 months. MAIN OUTCOME MEASURES: Percentage of participants with human complement serum bactericidal activity (hSBA) titer of 1:5 or greater against 3 MenB strains specific for vaccine antigens (NZ98/254, 44/76-SL, and 5/99). RESULTS: After three 4CMenB vaccinations, 99% or more of infants developed hSBA titers of 1:5 or greater against strains 44/76-SL and 5/99. For NZ98/254, this proportion was 79% (95% CI, 75.2%-82.4%) for vaccination at 2, 4, and 6 months with routine vaccines, 86.1% (95% CI, 82.9%-89.0%) for vaccination at 2, 4, and 6 months without routine vaccines, and 81.7% (95% CI, 76.6%-86.2%) for vaccination at 2, 3, and 4 months with routine vaccines. Responses to routine vaccines given with 4CMenB were noninferior to routine vaccines alone for all antigens, except for the responses to pertactin and serotype 6B pneumococcal polysaccharide. Fever was seen following 26% (158/602) to 41% (247/607) of 4CMenB doses when administered alone, compared with 23% (69/304) to 36% (109/306) after routine vaccines given alone and 51% (306/605) to 61% (380/624) after 4CMenB and routine vaccines administered together. CONCLUSION: A 4CMenB vaccine is immunogenic against reference strains when administered with routine vaccines at 2, 4, and 6 or at 2, 3, and 4 months of age, producing minimal interference with the response to routine infant vaccinations. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00721396. PMID- 22318279 TI - Cefpodoxime vs ciprofloxacin for short-course treatment of acute uncomplicated cystitis: a randomized trial. AB - CONTEXT: Although fluoroquinolones remain the most reliable urinary antimicrobial, resistance rates have increased and effective fluoroquinolone sparing antimicrobials are needed. OBJECTIVE: To determine whether cefpodoxime is noninferior to ciprofloxacin for treatment of acute cystitis. DESIGN, SETTING, AND PATIENTS: Randomized, double-blind trial of 300 women aged 18 to 55 years with acute uncomplicated cystitis comparing ciprofloxacin (n = 150) with cefpodoxime (n = 150); patients were from a student health center in Seattle, Washington, and a referral center in Miami, Florida. The study was conducted from 2005 to 2009 and outcomes were assessed at 5 to 9 days and 28 to 30 days after completion of therapy. Intent-to-treat and per-protocol analyses were performed; 15 women in the ciprofloxacin group and 17 women in the cefpodoxime group were lost to follow-up. INTERVENTIONS: Patients were given 250 mg of ciprofloxacin orally twice daily for 3 days or 100 mg of cefpodoxime proxetil orally twice daily for 3 days. MAIN OUTCOME MEASURES: Overall clinical cure (defined as not requiring antimicrobial treatment during follow-up) at the 30-day follow-up visit. Secondary outcomes were clinical and microbiological cure at the first follow-up visit and vaginal Escherichia coli colonization at each follow-up visit. The hypothesis that cefpodoxime would be noninferior to ciprofloxacin by a 10% margin (ie, for the difference in the primary outcome for ciprofloxacin minus cefpodoxime, the upper limit of the confidence interval would be <10%) was formulated prior to data collection. RESULTS: The overall clinical cure rate at the 30-day visit with the intent-to-treat approach in which patients lost to follow-up were considered as having clinical cure was 93% (139/150) for ciprofloxacin compared with 82% (123/150) for cefpodoxime (difference of 11%; 95% CI, 3%-18%); and for the intent-to-treat approach in which patients lost to follow-up were considered as having not responded to treatment, the clinical cure rate was 83% (124/150) for ciprofloxacin compared with 71% (106/150) for cefpodoxime (difference of 12%; 95% CI, 3%-21%). The microbiological cure rate was 96% (123/128) for ciprofloxacin compared with 81% (104/129) for cefpodoxime (difference of 15%; 95% CI, 8%-23%). At first follow-up, 16% of women in the ciprofloxacin group compared with 40% of women in the cefpodoxime group had vaginal E coli colonization. CONCLUSIONS: Among women with uncomplicated cystitis, a 3-day regimen of cefpodoxime compared with ciprofloxacin did not meet criteria for noninferiority for achieving clinical cure. These findings, along with concerns about possible adverse ecological effects associated with other broad-spectrum beta-lactams, do not support the use of cefpodoxime as a first line fluoroquinolone-sparing antimicrobial for acute uncomplicated cystitis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00194532. PMID- 22318280 TI - Association between age at diagnosis and disease-specific mortality among postmenopausal women with hormone receptor-positive breast cancer. AB - CONTEXT: In addition to classic tumor-related prognostic factors, patient characteristics may be associated with breast cancer outcome. OBJECTIVE: To assess the association between age at diagnosis and breast cancer outcome in postmenopausal women with hormone receptor-positive breast cancer. DESIGN, SETTING, AND PATIENTS: Study analysis of 9766 patients enrolled in the TEAM (Tamoxifen Exemestane Adjuvant Multinational) randomized clinical trial between January 2001 and January 2006. Age at diagnosis was categorized as younger than 65 years (n=5349), 65 to 74 years (n=3060), and 75 years or older (n=1357). MAIN OUTCOME MEASURES: Primary end point was disease-specific mortality; secondary end points were other-cause mortality and breast cancer relapse. RESULTS: During median follow-up of approximately 5.1 years, there were a total of 1043 deaths. Disease-specific mortality, as a proportion of all-cause mortality, decreased with categorical age group (78% [<65 years], 56% [65-74 years], and 36% [>=75 years]; P < .001). In multivariable analyses, compared with patients younger than 65 years, disease-specific mortality increased with age for patients aged 65 to 74 years (hazard ratio [HR], 1.25; 95% CI, 1.01-1.54); and patients aged 75 years or older (HR, 1.63; 95% CI, 1.23-2.16) (P < .001). Similarly, breast cancer relapse increased with age for patients aged 65-74 years (HR, 1.07; 95% CI, 0.91 1.25 and patients aged 75 years or older (HR, 1.29; 95% CI, 1.05-1.60) (P = .06). Other-cause mortality increased with age in patients aged 65 to 74 years (HR, 2.66; 95% CI, 1.96-3.63) and patients aged 75 years or older (HR, 7.30; 95% CI, 5.29-10.07) (P < .001). CONCLUSION: Among postmenopausal women with hormone receptor-positive breast cancer, increasing age was associated with a higher disease-specific mortality. PMID- 22318281 TI - Risk of intussusception following administration of a pentavalent rotavirus vaccine in US infants. AB - CONTEXT: Current rotavirus vaccines were not associated with intussusception in large prelicensure trials. However, recent postlicensure data from international settings suggest the possibility of a low-level elevated risk, primarily in the first week after the first vaccine dose. OBJECTIVE: To examine the risk of intussusception following pentavalent rotavirus vaccine (RV5) in US infants. DESIGN, SETTING, AND PATIENTS: This cohort study included infants 4 to 34 weeks of age, enrolled in the Vaccine Safety Datalink (VSD) who received RV5 from May 2006-February 2010. We calculated standardized incidence ratios (SIRs), relative risks (RRs), and 95% confidence intervals for the association between intussusception and RV5 by comparing the rates of intussusception in infants who had received RV5 with the rates of intussusception in infants who received other recommended vaccines without concomitant RV5 during the concurrent period and with the expected number of intussusception visits based on background rates assessed prior to US licensure of the RV5 (2001-2005). MAIN OUTCOME MEASURE: Intussusception occurring in the 1- to 7-day and 1- to 30-day risk windows following RV5 vaccination. RESULTS: During the study period, 786,725 total RV5 doses, which included 309,844 first doses, were administered. We did not observe a statistically significant increased risk of intussusception with RV5 for either comparison group following any dose in either the 1- to 7-day or 1- to 30-day risk window. For the 1- to 30-day window following all RV5 doses, we observed 21 cases of intussusception compared with 20.9 expected cases (SIR, 1.01; 95% CI, 0.62-1.54); following dose 1, we observed 7 cases compared with 5.7 expected cases (SIR, 1.23; 95% CI, 0.5-2.54). For the 1- to 7-day window following all RV5 doses, we observed 4 cases compared with 4.3 expected cases (SIR, 0.92; 95% CI, 0.25-2.36); for dose 1, we observed 1 case compared with 0.8 expected case (SIR, 1.21; 95% CI, 0.03-6.75). The upper 95% CI limit of the SIR (6.75) from the historical comparison translates to an upper limit for the attributable risk of 1 intussusception case per 65,287 RV5 dose-1 recipients. CONCLUSION: Among US infants aged 4 to 34 weeks who received RV5, the risk of intussusception was not increased compared with infants who did not receive the rotavirus vaccine. PMID- 22318282 TI - Does this patient have an infection of a chronic wound? AB - CONTEXT: Chronic wounds (those that have not undergone orderly healing) are commonly encountered, but determining whether wounds are infected is often difficult. The current reference standard for the diagnosis of infection of a chronic wound is a deep tissue biopsy culture, which is an invasive procedure. OBJECTIVES: To determine the accuracy of clinical symptoms and signs to diagnose infection in chronic wounds and to determine whether there is a preferred noninvasive method for culturing chronic wounds. DATA SOURCES: We searched multiple databases from inception through November 18, 2011, to identify studies focusing on diagnosis of infection in a chronic wound. STUDY SELECTION: Original studies were selected if they had extractable data describing historical features, symptoms, signs, or laboratory markers or were radiologic studies compared with a reference standard for diagnosing infection in patients with chronic wounds. Of 341 studies initially retrieved, 15 form the basis of this review. These studies include 985 participants with a total of 1056 chronic wounds. The summary prevalence of wound infection was 53%. DATA EXTRACTION: Three authors independently assigned each study a quality grade, using previously published criteria. One author abstracted operating characteristic data. DATA SYNTHESIS: An increase in the level of pain (likelihood ratio range, 11-20) made infection more likely, but its absence (negative likelihood ratio range, 0.64 0.88) did not rule out infection. Other items in the history and physical examination, in isolation or in combination, appeared to have limited utility when infection was diagnosed in chronic wounds. Routine laboratory studies had uncertain value in predicting infection of a chronic wound. CONCLUSIONS: The presence of increasing pain may make infection of a chronic wound more likely. Further evidence is required to determine which, if any, type of quantitative swab culture is most diagnostic. PMID- 22318283 TI - Rash in an immunocompromised patient. PMID- 22318284 TI - Inching toward a serogroup B meningococcal vaccine for infants. PMID- 22318285 TI - JAMA patient page. Intussusception. PMID- 22318286 TI - Urokinase-type plasminogen activator and plasminogen mediate activation of macrophage phagocytosis during liver repair in vivo. AB - Urokinase-type plasminogen activator (u-PA) and plasminogen play a primary role in liver repair through the accumulation of macrophages and alteration of their phenotype. However, it is still unclear whether u-PA and plasminogen mediate the activation of macrophage phagocytosis during liver repair. Herein, we investigated the morphological changes in macrophages that accumulated at the edge of damaged tissue induced by a photochemical reaction or hepatic ischaemia reperfusion in mice with u-PA ( u-PA-/- ) or plasminogen ( Plg-/- ) gene deficiency by using transmission electron and fluorescence microscopy. In wild type mice, the macrophages aligned at the edge of the damaged tissue and extended a large number of long pseudopodia. These macrophages clearly engulfed cellular debris and showed well-developed organelles, including lysosome-like vacuoles, nuclei, and Golgi complexes. In wild-type mice, the distribution of the Golgi complex in these macrophages was biased towards the direction of the damaged tissue, indicating the extension of their pseudopodia in this direction. Conversely, in u-PA-/- and Plg-/- mice, the macrophages located at the edge of the damaged tissue had few pseudopodia and less developed organelles. The Golgi complex was randomly distributed in these macrophages in u-PA-/- mice. Furthermore, interferon gamma and IL-4 were expressed at a low level at the border region of the damaged tissue in u-PA-/- mice. Our data provide novel evidence that u-PA and plasminogen are essential for the phagocytosis of cellular debris by macrophages during liver repair. Furthermore, u-PA plays a critical role in the induction of macrophage polarity by affecting the microenvironment at the edge of damaged tissue. PMID- 22318287 TI - The Trouble with Being Sincere. PMID- 22318289 TI - Prostate cancer: PSA screening--more data, more debate. PMID- 22318290 TI - Social Support from Sponsorships as a Moderator of Acculturative Stress: Predictors of Effects on Refugees and Asylum Seekers. AB - N = 63 refugees and asylum seekers, 27 women and 36 men with a mean age of 33.08 years (SD = 10.3) from Chechnya and Afghanistan were granted sponsorships for six months and were randomized to an intervention and a waiting-list control group. Only participants with a history of traumatization benefited from the intervention. For the traumatized sub-sample, sponsorships led to a significant and stable decrease in anxiety, depression, and psychological problems as compared to the control group, with effect sizes comparable to those of psychotherapy. The effects being rather palliative than instrumental, however, sponsorships did not instigate improvements in acculturation, societal contact, or coping capability. Women benefited more from the intervention than men, and Afghans more than Chechen. PMID- 22318291 TI - Measurement of antifungal drug levels in cerebrospinal fluid for cryptococcal meningoencephalitis. AB - We report a rare case of cryptococcal meningoencephalitis in which antifungal therapy was monitored by measuring the cerebrospinal fluid (CSF) levels of the antifungal drugs. A 78-year-old man with diabetes mellitus being treated with oral agents. He had no history of human immunodeficiency virus infection. The patient showed abnormal behavior and fever (>38 degrees C) on November 20, 2009, and was admitted for disturbance of consciousness on November 24. CSF examination showed an increased cell count, and a yeast-like fungus, suggesting cryptococcal meningoencephalitis, was observed by India ink staining. Initial treatment was liposomal amphotericin B (L-AMB) plus flucytosine. Cryptococcus neoformans was isolated by CSF culture on day 2. MIC was 0.25 MUg/ml for amphotericin B (AMPH B), 4 MUg/ml for flucytosine, 4 MUg/ml for fluconazole (FLCZ), and 0.03 MUg/ml for voriconazole (VRCZ). Despite treatment, his disturbance of consciousness persisted. The CSF level of AMPH-B was <=0.05 MUg/ml on day 8. Therefore, L-AMB was switched to fosfluconazole. The CSF level of FLCZ was sufficient (22.6 MUg/ml) on day 25, but there was a decrease in glucose and the fungus could still be detected in CSF smears. Consequently, FLCZ was switched to VRCZ. On day 47, CSF level of VRCZ was 1.97 MUg/ml, exceeding its MIC, so treatment was continued. On day 77, the patient was generally lucid, and CSF smears did not detect any fungi. The patient was then transferred for rehabilitation. On day 84, voriconazole was discontinued, with no evidence of fungal recurrence. PMID- 22318292 TI - A case report: successful pregnancy after controlled ovarian hyperstimulation by using short-acting gonadotropin releasing hormone agonist only. PMID- 22318293 TI - Effect of male age on the outcome of in vitro fertilization: oocyte donation as a model. AB - PURPOSE: To assess the influence of male age on the outcome of oocyte donation cycles. MATERIALS AND METHODS: A total 103 oocyte donation cycles of 70 couples (male aged 26 to 57) were examined, all of which were performed with conventional in vitro fertilization using fresh ejaculation sperm. Main outcome measures were fertilization rate, clinical pregnancy, live birth rates and pregnancy loss. RESULTS: A total 122 cryopreserved embryo transfer were performed, resulting in 34 cycles resulted in clinical pregnancy and 27 live births. No significant correlation was found between male age and fertilization rate. No significant difference was found in male age between the patients who achieved clinical pregnancy and live birth and those who did not. All the pregnancy loss occurred in cycles where the male was older than 37, however, when the cycles were divided into two groups according to whether or not male age older than 37, no statistically significant difference was not found in pregnancy loss rate. CONCLUSIONS: Aging of the male has no significant impact on fertilization, pregnancy or live birth in oocyte donation cycles, but may be associated with pregnancy loss. PMID- 22318294 TI - Case report: elevated sperm aneuploidy levels in an infertile Robertsonian translocation t(21;21) carrier with possible interchromosomal effect. PMID- 22318295 TI - Patient confidentiality and treating physician participation in informal interviews with defense counsel: guidance and recommendations. PMID- 22318296 TI - Promoting breastfeeding in the healthcare environment. PMID- 22318297 TI - Responding to requests for non-beneficial treatment. PMID- 22318298 TI - Announcing the 2012 Edward J. III Excellence in Medicine Awards(r). PMID- 22318299 TI - Challenges to diagnosis and treatment of depression in men. PMID- 22318300 TI - Travel-related health risks part 1: trauma and complications from underlying health problems. PMID- 22318301 TI - Facebook dos and don'ts for medical professionals. PMID- 22318302 TI - Rabies shots, the Newark boys and the American origins of the modern medical breakthrough. PMID- 22318303 TI - Point of view: national guidelines to manage sports-related concussions and New Jersey legislation extended to cheerleaders: important wins for student-athletes. PMID- 22318304 TI - Biogeochemical conditions determine virulence of black band disease in corals. AB - The microenvironmental dynamics of the microbial mat of black band disease (BBD) and its less virulent precursor, cyanobacterial patch (CP), were extensively profiled using microsensors under different light intensities with respect to O(2), pH and H(2)S. BBD mats exhibited vertical stratification into an upper phototrophic and lower anoxic and sulphidic zone. At the progression front of BBD lesions, high sulphide levels up to 4977 MUM were measured in darkness along with lower than ambient levels of pH (7.43+/-0.20). At the base of the coral-BBD microbial mat, conditions were hypoxic or anoxic depending on light intensity exposure. In contrast, CP mats did not exhibit strong microchemical stratification with mostly supersaturated oxygen conditions throughout the mats at all light intensities and with levels of pH generally higher than in BBD. Two of three replicate CP mats were devoid of sulphide, while the third replicate showed only low levels of sulphide (up to 42 MUM) present in darkness and at intermediate light levels. The level of oxygenation and sulphide correlated well with lesion migration rates, that is virulence of the mats, which were greater in BBD than in CP. The results suggest that biogeochemical microgradients of BBD shaped by the complex microbial community, rather than a defined pathogen, are the major trigger for high virulence and the associated derived coral mortality of this disease. PMID- 22318305 TI - Global distribution and diversity of marine Verrucomicrobia. AB - Verrucomicrobia is a bacterial phylum that is commonly detected in soil, but little is known about the distribution and diversity of this phylum in the marine environment. To address this, we analyzed the marine microbial community composition in 506 samples from the International Census of Marine Microbes as well as 11 coastal samples taken from the California Current. These samples from both the water column and sediments covered a wide range of environmental conditions. Verrucomicrobia were present in 98% of the analyzed samples, and thus appeared nearly ubiquitous in the ocean. Based on the occurrence of amplified 16S ribosomal RNA sequences, Verrucomicrobia constituted on average 2% of the water column and 1.4% of the sediment bacterial communities. The diversity of Verrucomicrobia displayed a biogeography at multiple taxonomic levels and thus, specific lineages appeared to have clear habitat preference. We found that subdivision 1 and 4 generally dominated marine bacterial communities, whereas subdivision 2 was more frequent in low salinity waters. Within the subdivisions, Verrucomicrobia community composition were significantly different in the water column compared with sediment as well as within the water column along gradients of salinity, temperature, nitrate, depth and overall water column depth. Although we still know little about the ecophysiology of Verrucomicrobia lineages, the ubiquity of this phylum suggests that it may be important for the biogeochemical cycle of carbon in the ocean. PMID- 22318306 TI - Protective effects of thymoquinone on vancomycin-induced nephrotoxicity in rats. AB - AIM: Oxidative stress has been implicated as a potential responsible mechanism in the pathogenesis of vancomycin (VCM)-induced renal toxicity. Therefore, we aimed to investigate the protective effect of thymoquinone (TQ) against VCM-induced nephrotoxicity by tissue oxidant/antioxidant parameters and histological changes in rats. MATERIALS AND METHODS: Wistar albino rats were randomly separated into four groups consisting of seven rats per group. The groups had normal saline (control group), VCM, VCM and TQ and TQ, respectively. VCM was injected intraperitoneally at a dose of 200 mg/kg and continued at 12-h intervals for 7 days. TQ was injected intraperitoneally at a dose of 10 mg/kg and continued at 24 h intervals for 8 days. Animals were killed and blood samples were analyzed for the levels of serum blood urea nitrogen (BUN) and creatinine (Cr). Kidney specimens were analyzed for levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as for histopathological changes. RESULTS: We found that the levels of serum BUN, Cr and kidney tissue MDA were increased in the VCM group. Activities of SOD and GSH-Px in kidney tissue were decreased. TQ administration ameliorated significantly these changes. CONCLUSION: These results indicate that the TQ produces a protective mechanism against VCM-induced nephrotoxicity and suggest a role of oxidative stress in pathogenesis. PMID- 22318307 TI - D-Limonene modulates inflammation, oxidative stress and Ras-ERK pathway to inhibit murine skin tumorigenesis. AB - D-Limonene, a common monoterepene has been shown to have antiproliferative, apoptosis-inducing and chemopreventive effects. In the present study, we have investigated the effects of D-limonene on the growth of 7,12 dimethylbenz[a]anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13 acetate (TPA)-promoted skin tumor development. We found that D-limonene (50 and 100 mg/kg body weight) treatments to the mouse skin significantly reduced the TPA induced (a) edema and hyperplasia (p < 0.001); (b) expression of cyclooxygenase 2; (c) ornithine decarboxylase activity (p < 0.001); and (d) [(3)H] thymidine incorporation into DNA (p < 0.001). In addition, treatment of D-limonene effectively restored the level of reduced glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, catalase and malondialdehyde production in TPA-treated mouse skin. In a two-stage skin tumorigenesis study, D limonene significantly reduced the tumor burden (p < 0.005) and tumor incidence as compared to DMBA/TPA-treated mice. D-Limonene treatment also extended the latency period of tumor development from 4 to 9 weeks. D-Limonene treatment decreased the expression level of Ras, Raf and phosphorylation of extracellular signal-regulated protein kinase 1/2 in DMBA/TPA-induced tumors. A decrease in the expression of Bcl-2 and an increase in Bax expression were also observed in tumor tissues of mice treated with D-limonene. Taken together, our findings suggest that D-limonene may exert its chemopreventive activity through the inhibition of inflammation, oxidative stress and Ras-signaling as well as the induction of pro apoptotic state during TPA-mediated promotion of DMBA-induced skin cancer in mouse model. PMID- 22318308 TI - Protective effect of curcumin, silymarin and N-acetylcysteine on antitubercular drug-induced hepatotoxicity assessed in an in vitro model. AB - Tuberculosis (TB) is highly endemic in India. The first-line anti-TB therapy (ATT) involving isoniazid (INH), rifampicin and pyrazinamide causes hepatotoxicity in approximately 11.5% of Indian patients. Studies have shown that ATT-induced hepatotoxicity is primarily due to oxidative stress caused by the drugs and metabolites. Herbal drugs with antioxidative properties have been tested in animal studies and clinical trials for the management of hepatotoxicity. The objective of this study was to investigate the role of curcumin (CUR), silymarin (SILY) and N-acetylcysteine (N-ACET) on hepatotoxicity by ATT drugs using an in vitro model of human hepatocellular carcinoma cell line (HepG2). HepG2 cells were treated with ATT drugs alone or along with CUR, SILY or N-ACET for a 48-h duration. The cells were monitored for viability, morphology, respiring mitochondria and cell cycle. Our results suggest that the presence of hepatoprotective drugs during treatment of HepG2 cells with ATT drugs lowers the hepatotoxic effect of the latter. This is observed in terms of (a) increased cell viability, (b) healthy-looking cell morphology as revealed by phase contrast microscopy, (c) active respiring cells as observed with confocal microscopy upon staining with a mitochondrial membrane-specific dye, MitoTracker((r)) Red, and reduction in the sub-G(1) peak in cell cycle analysis by flow cytometry. Our results suggest that these hepatoprotective drugs need to be further explored as potential adjuvant therapy along with ATT drugs. PMID- 22318309 TI - Bio-monitoring for uranium using stream-side terrestrial plants and macrophytes. AB - This study evaluated the abilities of various plant species to act as bio monitors for environmental uranium (U) contamination. Vegetation and soil samples were collected from a U processing facility. The water-way fed from facility storm and processing effluents was the focal sample site as it represented a primary U transport mechanism. Soils and sediments from areas exposed to contamination possessed U concentrations that averaged 630 mg U kg(-1). Aquatic mosses proved to be exceptional accumulators of U with dry weight (dw) concentrations measuring as high as 12,500 mg U kg(-1) (approximately 1% of the dw mass was attributable to U). The macrophytes (Phragmites communis, Scripus fontinalis and Sagittaria latifolia) were also effective accumulators of U. In general, plant roots possessed higher concentrations of U than associated upper portions of plants. For terrestrial plants, the roots of Impatiens capensis had the highest observed levels of U accumulation (1030 mg kg(-1)), followed by the roots of Cyperus esculentus and Solidago speciosa. The concentration ratio (CR) characterized dry weight (dw) vegetative U levels relative to that in associated dw soil. The plant species that accumulated U at levels in excess of that found in the soil were: P. communis root (CR, 17.4), I. capensis root (CR, 3.1) and S. fontinalis whole plant (CR, 1.4). Seven of the highest ten CR values were found in the roots. Correlations with concentrations of other metals with U were performed, which revealed that U concentrations in the plant were strongly correlated with nickel (Ni) concentrations (correlation: 0.992; r-squared: 0.984). Uranium in plant tissue was also strongly correlated with strontium (Sr) (correlation: 0.948; r-squared: 0.899). Strontium is chemically and physically similar to calcium (Ca) and magnesium (Mg), which were also positively-correlated with U. The correlation with U and these plant nutrient minerals, including iron (Fe), suggests that active uptake mechanisms may influence plant U accumulation. PMID- 22318311 TI - The impact of obesity on balance control in community-dwelling older women. AB - Older individuals have impaired balance control, particularly those that are frail and/or have sensory deprivations. Obese individuals show faster body sway during upright stance than normal weight individuals, suggesting that they also have difficulty controlling balance even if they do not have the same sensory issues as the older people. Therefore, the objective of this study was to examine if obesity is associated to a decreased balance control in older women. Postural sway of normal weight (n = 15, age = 70.8 +/- 5.5 years; BMI = 22.2 +/- 1.9 kg/m(2)), overweight (n = 15, age = 71.7 +/- 4.3 years; BMI = 27.3 +/- 1.3 kg/m(2)), and obese (n = 15, age = 71.1 +/- 4.3 years; BMI = 33.1 +/- 3.4 kg/m(2)) women was measured with a force platform for normal quiet stance lasting for 30 s in opened and closed eyes conditions. The obese group oscillated at a faster speed than the normal weight group (vision 0.99 +/- 0.29 cm/s vs. 0.70 +/- 0.16 cm/s, p < 0.01; no vision 1.43 +/- 0.50 cm/s vs. 0.87 +/- 0.23 cm/s, p < 0.01). The obese group exhibited greater range in both axes without vision compared to the normal weight group (p < 0.05). When observing sway density parameters, the obese group also spent less time in stability zones (2 mm radius area in which the center of pressure is relatively stable), and the distance between these stability zones are greater than the normal weight group in both visual conditions (p < 0.01 and p < 0.05, respectively). Obesity clearly affects postural control in older women. Our results suggest that obesity has a negative impact on the capacity of older woman to adequately use proprioceptive information for posture control. As postural instability or balance control deficits are identified as a risk factor for falling, our results also suggest that obesity in older women could be considered as another potential contributing factor for falling. PMID- 22318312 TI - Prediction of thrombus resolution after intravenous thrombolysis assessed by CT based thrombus imaging. AB - The degree of thrombus resolution directly indicates the effectiveness of a thrombolytic drug. We investigated the degree of thrombus resolution and factors associated with thrombus resolution after intravenous (IV) recombinant tissue plasminogen activator (rt-PA) using thin-section noncontrast computed tomography (NCT). Thin-section NCTs were performed before and immediately after IV rt-PA infusion in acute stroke patients. The thrombus volume and Hounsfield unit were measured using three-dimensional imaging software. Immediate recanalisation was assessed immediately after IV rt-PA infusion using CT angiography. During a three year study period, 130 patients were prospectively enrolled. On baseline thin section NCT, no thrombi were found in 30 patients (23%). Among the 100 patients with confirmed thrombus, the median volume decreased by 20% on the follow-up NCT. The thrombus was completely resolved in 8%. Of note, an increase in thrombus volume was observed in 20 patients. Independent predictors of thrombus resolution were total rt-PA dose, thrombus location in the M2 segment of the middle cerebral artery, and time from baseline to follow-up NCT. Thrombus resolution increased by 9% per each 10-mg increase in rt-PA (p = 0.045). Immediate complete recanalisation was achieved in 12% of patients. Total dose of rt-PA was independently associated with complete recanalisation [odds ratio [OR] 4.52, 95% confidence interval [CI] 1.345-15.184) and good functional outcome at three months (modified Rankin scale score <3, OR 2.34, 95% CI 1.104-4.962). In conclusion, rt-PA dose was associated with the degree of thrombus resolution, immediate complete recanalisation, and good outcome at three months. CT-based thrombus imaging may be helpful in determining thrombolysis effectiveness. PMID- 22318313 TI - Young adults' performance in a low-intensity weight loss campaign. AB - Young adults (YA) are underrepresented in behavioral weight loss programs and achieve poorer outcomes than older adults (OA). There has been a call to develop programs specifically targeting this age group. This study examined the performance of YA enrolled in a low-intensity, team-based weight loss campaign and compared their outcomes to OA to determine the utility of such an approach for weight loss in this population. Shape Up Rhode Island (SURI) 2009 was a 12 week online team-based weight loss and exercise competition (N = 6,795, 81% female, 94% white, age = 44.7 +/- 11.2, BMI = 29.4 +/- 5.9). YA was defined as 18 35 years and OA as >35 years; YA and OA were compared on enrollment, retention, weight loss, and change in steps. A total of 1,562 YA enrolled and 715 completed the program. Fewer YA completed compared with OA (46 vs. 62%, P < 0.001). However, among completers, YA achieved greater percent weight loss (-4.5 +/- 4.0 vs. -3.8 +/- 3.2%) and greater daily step change (+1,578.2 +/- 3,877.2 vs. +1,342.2 +/- 3,645.7) than OA (P's < 0.001). Further, more YA completers achieved a >= 5% weight loss (40 vs. 29%, P < 0.001). Findings were consistent in the overweight/obese (OW/OB) subsample, and using <= 25 years of age as the cut off for YA. Weight losses among YA in this low-intensity weight loss campaign were quite promising, with over 700 YA completing the program and on average achieving a 4.5% weight loss. Indeed, the potential public health impact of such an approach is substantial; future efforts to develop programs for this age group may benefit from using a low-intensity, team-based approach. PMID- 22318314 TI - Escalating coverage of obesity in UK newspapers: the evolution and framing of the "obesity epidemic" from 1996 to 2010. AB - Obesity is one of the fastest growing and most serious public health challenges facing the world in the 21st century. Correspondingly, over the past decade there has been increased interest in how the obesity epidemic has been framed by the media. This study offers the first large-scale examination of the evolution and framing of the obesity epidemic in UK newspapers, identifying shifts in news coverage about the causal drivers of and potential solutions to the obesity epidemic. Seven UK newspapers were selected and 2,414 articles published between 1 January 1996 and 31 December 2010 were retrieved from electronic databases using keyword searches. The thematic content of articles was examined using manifest content analysis. Over the 15-year period there was an increase in media reporting on obesity and in particular on childhood obesity. There was evidence of a trend away from a focus on individuals towards a greater level of reporting on societal solutions such as regulatory change, with the greatest shift in reporting occurring in mid-market and serious newspapers. Given that the media have a huge influence in shaping public opinion, this shift in reporting might be an early indicator to policymakers of a growing public discourse around a need for regulatory change to tackle the obesogenic environment. PMID- 22318315 TI - Adropin deficiency is associated with increased adiposity and insulin resistance. AB - Adropin is a secreted peptide that improves hepatic steatosis and glucose homeostasis when administered to diet-induced obese mice. It is not clear if adropin is a peptide hormone regulated by signals of metabolic state. Moreover, the significance of a decline in adropin expression with obesity with respect to metabolic disease is also not clear. We investigated the regulation of serum adropin by metabolic status and diet. Serum adropin levels were high in chow-fed conditions and were suppressed by fasting and diet-induced obesity (DIO). High adropin levels were observed in mice fed a high-fat low carbohydrate diet, whereas lower levels were observed in mice fed a low-fat high carbohydrate diet. To investigate the role of adropin deficiency in metabolic homeostasis, we generated adropin knockout mice (AdrKO) on the C57BL/6J background. AdrKO displayed a 50%-increase in increase in adiposity, although food intake and energy expenditure were normal. AdrKO also exhibited dyslipidemia and impaired suppression of endogenous glucose production (EndoR(a)) in hyperinsulinemic euglycemic clamp conditions, suggesting insulin resistance. While homo- and heterozygous carriers of the null adropin allele exhibited normal DIO relative to controls, impaired glucose tolerance associated with weight gain was more severe in both groups. In summary, adropin is a peptide hormone regulated by fasting and feeding. In fed conditions, adropin levels are regulated dietary macronutrients, and increase with dietary fat content. Adropin is not required for regulating food intake, however, its functions impact on adiposity and are involved in preventing insulin resistance, dyslipidemia, and impaired glucose tolerance. PMID- 22318316 TI - Lentiviral vector mediates exogenous gene expression in adult rat DRG following peripheral nerve remote delivery. AB - The primary sensory neurons with cell bodies in the dorsal root ganglion (DRG) have been extensively used as models in neurobiology and provide a useful model to study the mechanism of neural regeneration. Therefore, efficient and stable gene delivery to these postmitotic cells has significant therapeutic potential. Various studies involving the viral vector systems capable of neuronal transduction have been extensively evaluated in the cultured DRG neurons by adeno associated virus. In the present study, we investigated the transduction performance of the lentiviral vector that mediates the catalytic subunit of protein kinase A (PKAc) and green fluorescent protein (GFP) expression in the DRG by sciatic nerve retrograde transport and tested whether PKAc expression in the DRG could inhibit the activation of RhoA after spinal cord injury. Five days after sciatic nerve remote delivery of lentiviral vector (LV)/PKAc-internal ribosome entry site (IRES)-GFP or LV/GFP, the L4-L6 DRGs were dissected for primary culture or immunostaining to observe the exogenous gene expression, or transecting the dorsal part of lumbar enlargement was performed, and 16 h later, the function of the exogenous gene was tested by RhoA pull-down analysis. The results showed that the lentiviral vector could mediate exogenous gene PKAc expression in the DRG and then inhibit spinal cord injury-induced RhoA activation by remote delivery of LV/PKAc-IRES-GFP through the sciatic nerve. PMID- 22318317 TI - Role of complement in dengue virus infection: protection or pathogenesis? AB - Dengue viruses (DENV) cause a spectrum of disease in humans, ranging from dengue fever (DF) to a severe, life-threatening syndrome called dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Despite the global morbidity and mortality associated with DENV infection, mechanisms of immune control and viral pathogenesis are poorly understood. In a recent article, Avirutnan et al. [mBio 2(6):e00276-11, 2011] demonstrated that DENV can be directly neutralized via the mannose binding lectin (MBL) pathway of the complement system and that deficiency in MBL level or activity due to host polymorphisms in the MBL2 gene correlates with reduced levels of DENV neutralization. These findings implicate a role for the MBL pathway in controlling DENV infections and modulating DHF/DSS manifestations. PMID- 22318318 TI - A critical phenylalanine residue in the respiratory syncytial virus fusion protein cytoplasmic tail mediates assembly of internal viral proteins into viral filaments and particles. AB - Respiratory syncytial virus (RSV) is a single-stranded RNA virus in the Paramyxoviridae family that assembles into filamentous structures at the apical surface of polarized epithelial cells. These filaments contain viral genomic RNA and structural proteins, including the fusion (F) protein, matrix (M) protein, nucleoprotein (N), and phosphoprotein (P), while excluding F-actin. It is known that the F protein cytoplasmic tail (FCT) is necessary for filament formation, but the mechanism by which the FCT mediates assembly into filaments is not clear. We hypothesized that the FCT is necessary for interactions with other viral proteins in order to form filaments. In order to test this idea, we expressed the F protein with cytoplasmic tail (CT) truncations or specific point mutations and determined the abilities of these variant F proteins to form filaments independent of viral infection when coexpressed with M, N, and P. Deletion of the terminal three FCT residues (amino acids Phe-Ser-Asn) or mutation of the Phe residue resulted in a loss of filament formation but did not affect F-protein expression or trafficking to the cell surface. Filament formation could be restored by addition of residues Phe-Ser-Asn to an FCT deletion mutant and was unaffected by mutations to Ser or Asn residues. Second, deletion of residues Phe Ser-Asn or mutation of the Phe residue resulted in a loss of M, N, and P incorporation into virus-like particles. These data suggest that a C-terminal Phe residue in the FCT mediates assembly through incorporation of internal virion proteins into virus filaments at the cell surface. IMPORTANCE: Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis and pneumonia in infants and the elderly worldwide. There is no licensed RSV vaccine and only limited therapeutics for use in infected patients. Many aspects of the RSV life cycle have been studied, but the mechanisms that drive RSV assembly at the cell surface are not well understood. This study provides evidence that a specific residue in the RSV fusion protein cytoplasmic tail coordinates assembly into viral filaments by mediating the incorporation of internal virion proteins. Understanding the mechanisms that drive RSV assembly could lead to targeted development of novel antiviral drugs. Moreover, since RSV exits infected cells in an ESCRT (endosomal sorting complexes required for transport)-independent manner, these studies may contribute new knowledge about a general strategy by which ESCRT-independent viruses mediate outward bud formation using viral protein mediated mechanisms during assembly and budding. PMID- 22318319 TI - Host cell nucleolin is required to maintain the architecture of human cytomegalovirus replication compartments. AB - Drastic reorganization of the nucleus is a hallmark of herpesvirus replication. This reorganization includes the formation of viral replication compartments, the subnuclear structures in which the viral DNA genome is replicated. The architecture of replication compartments is poorly understood. However, recent work with human cytomegalovirus (HCMV) showed that the viral DNA polymerase subunit UL44 concentrates and viral DNA synthesis occurs at the periphery of these compartments. Any cellular factors involved in replication compartment architecture are largely unknown. Previously, we found that nucleolin, a major protein component of nucleoli, associates with HCMV UL44 in infected cells and is required for efficient viral DNA synthesis. Here, we show that nucleolin binds to purified UL44. Confocal immunofluorescence analysis demonstrated colocalization of nucleolin with UL44 at the periphery of replication compartments. Pharmacological inhibition of viral DNA synthesis prevented the formation of replication compartments but did not abrogate association of UL44 and nucleolin. Thus, association of UL44 and nucleolin is unlikely to be a nonspecific effect related to development of replication compartments. No detectable colocalization of 5-ethynyl-2'-deoxyuridine (EdU)-labeled viral DNA with nucleolin was observed, suggesting that nucleolin is not directly involved in viral DNA synthesis. Small interfering RNA (siRNA)-mediated knockdown of nucleolin caused improper localization of UL44 and a defect in EdU incorporation into viral DNA. We propose a model in which nucleolin anchors UL44 at the periphery of replication compartments to maintain their architecture and promote viral DNA synthesis. IMPORTANCE: Human cytomegalovirus (HCMV) is an important human pathogen. HCMV infection causes considerable rearrangement of the structure of the nucleus, largely due to the formation of viral replication compartments within the nucleus. Within these compartments, the virus replicates its DNA genome. We previously demonstrated that nucleolin is required for efficient viral DNA synthesis and now find that the nucleolar protein nucleolin interacts with a subunit of the viral DNA polymerase, UL44, specifically at the periphery of replication compartments. Moreover, we find that nucleolin is required to properly localize UL44 at this region. Nucleolin is, therefore, involved in the organization of proteins within replication compartments. This, to our knowledge, is the first report identifying a cellular protein required for maintaining replication compartment architecture. PMID- 22318320 TI - Kinetics of uropathogenic Escherichia coli metapopulation movement during urinary tract infection. AB - The urinary tract is one of the most frequent sites of bacterial infection in humans. Uropathogenic Escherichia coli (UPEC) strains are the leading cause of urinary tract infections (UTIs) and are responsible for greater than 80% of uncomplicated cases in adults. Infection of the urinary tract occurs in an ascending manner, with colonization of the bladder leading to possible kidney infection and bacteremia. The goal of this study was to examine the population dynamics of UPEC in vivo using a murine model of ascending UTI. To track individual UPEC lineages within a host, we constructed 10 isogenic clones of UPEC strain CFT073 by inserting unique signature tag sequences between the pstS and glmS genes at the attTn7 chromosomal site. Mice were transurethrally inoculated with a mixture containing equal numbers of unique clones. After 4 and 48 h, the tags present in the bladders, kidneys, and spleens of infected mice were enumerated using tag-specific primers and quantitative real-time PCR. The results indicated that kidney infection and bacteremia associated with UTI are most likely the result of multiple rounds of ascension and dissemination from motile UPEC subpopulations, with a distinct bottleneck existing between the kidney and bloodstream. The abundance of tagged lineages became more variable as infection progressed, especially after bacterial ascension to the upper urinary tract. Analysis of the population kinetics of UPEC during UTI revealed metapopulation dynamics, with lineages that constantly increased and decreased in abundance as they migrated from one organ to another. IMPORTANCE: Urinary tract infections are some of the most common infections affecting humans, and Escherichia coli is the primary cause in most uncomplicated cases. These infections occur in an ascending manner, with bacteria traveling from the bladder to the kidneys and potentially the bloodstream. Little is known about the spatiotemporal population dynamics of uropathogenic E. coli within a host. Here we describe a novel approach for tracking lineages of isogenic tagged E. coli strains within a murine host by the use of quantitative real-time PCR. Understanding the in vivo population dynamics and the factors that shape the bacterial population may prove to be of significant value in the development of novel vaccines and drug therapies. PMID- 22318322 TI - Chiral flavanones from Amygdalus lycioides Spach: structural elucidation and identification of TNFalpha inhibitors by bioactivity-guided fractionation. AB - Phytochemical investigation on the Amygdalus lycioides Spach branchelets resulted in the isolation of four chiral flavanones: (2R,3R)-Taxifolin, (2R,3R) aromadendrin, (S)-5,7,3',5'-tetrahydroxyflavanone and (S)-naringenin. The flavanones were isolated by semi-preparative HPLC, their structures elucidated based on spectroscopic data and their absolute configuration assigned. As a part of our ethnobotanical-directed search for novel TNFalpha inhibitors, the bioassay guided fractionation of the n-hexane-acetone (n-Hex-Ac, 1:1 v/v) Amygdalus lycioides Spach branchelets extract was performed. In this way, (S)-naringenin was identified as the constituent responsible for the TNFalpha blocking effect, being effective in vitro and in vivo after oral administration. This is the first investigation on bioactive secondary metabolites of Amygdalus lycioides Spach branchelets. PMID- 22318323 TI - Multicomponent synthesis of 3,6-dihydro-2H-1,3-thiazine-2-thiones. AB - Non-fused 3,6-dihydro-2H-1,3-thiazine-2-thiones constitute a so far rather unexplored class of compounds, with the latest report dating back more than two decades. Thiazine-2-thiones contain an endocyclic dithiocarbamate group, which is often found in pesticides, in substrates for radical chemistry and in synthetic intermediates towards thioureas and amidines. We now report the multicomponent reaction (MCR) of in situ-generated 1-azadienes with carbon disulfide. With this reaction, a one-step protocol towards the potentially interesting 3,6-dihydro-2H 1,3-thiazine-2-thiones was established and a small library was synthesized. PMID- 22318324 TI - Phytochemical and antioxidant-related investigations on bark of Abies spectabilis (D. Don) Spach. from Nepal. AB - The bark of several coniferous species, a waste product of the timber industry, contains significant amounts of natural antioxidants. In our ongoing studies of Nepalese medicinal plants, we examined the bark from Abies spectabilis as the starting material for extracting antioxidant compounds. In vitro antioxidant activity evaluated by means of three antioxidant methods, namely 2,2-diphenyl-1 picrylhydrazyl (DPPH), Briggs-Rauscher oscillating reaction (BR) and Trolox Equivalent Antioxidant Capacity (TEAC) and total phenol contents with the Folin Ciocalteau reagent; the ferrous iron chelating capacity was also assessed. The methanol extract of A. spectabilis showed significant antioxidant activity and polyphenol contents (IC(50) 4.13 ug/mL, 0.20 MUg/mL eq. resorcinol, 4.22 mM eq. Trolox, 3.9 ug/g eq. gallic Acid in the DPPH, BR, TEAC and Folin-Ciocalteau tests, respectively) and weak Fe(2+) chelating capacity. Phytochemical studies were also carried out with 1D- and 2D NMR experiments and DI-ESI-MS, HPLC-DAD and LC-MSn measurements. Oligomeric C-type proanthocyanidins, mainly trimeric gallocatechin derivatives, were the most abundant compounds (16% of extract expressed as procyanindin B1). Gallocatechin oligomers (up to six units) and prodelphynidin-gallocatechin polymers were also identified in the extract. Prodelphynidin B4, cyclograndisolide and trans-docosanil ferulate were also isolated and characterized by NMR and MS spectroscopy. PMID- 22318325 TI - Statistical platform to discern spatial and temporal coordination of endothelial sprouting. AB - Many biological processes, including angiogenesis, involve intercellular feedback and temporal coordination, but inference of these relations is often drowned in low sample sizes or noisy population data. To address this issue, a methodology was developed to statistically study spatial lateral inhibition and temporal synchronization in one specific biological process, endothelial sprouting mediated by Notch signaling. Notch plays an essential role in the development of organized vasculature, but the effects of Notch on the temporal characteristics of angiogenesis are not well understood. Results from this study showed that Notch lateral inhibition operates at distances less than 31 MUm. Furthermore, combining time lapse microscopy with an intraclass correlation model typically used to analyze family data showed intrinsic temporal synchronization among endothelial sprouts originating from the same microcarrier. Such synchronization was reduced with Notch inhibitors, but was enhanced with the addition of Notch ligands. These results indicate that Notch plays a critical role in the temporal regulation of angiogenesis, as well as spatial control, and this method of analysis will be of significant utility in studies of a variety of other biological processes. PMID- 22318326 TI - Adjuvant intensity-modulated proton therapy in malignant pleural mesothelioma. A comparison with intensity-modulated radiotherapy and a spot size variation assessment. AB - PURPOSE: Intensity-modulated radiation therapy (IMRT) is the state-of-the-art treatment for patients with malignant pleural mesothelioma (MPM). The goal of this work was to assess whether intensity-modulated proton therapy (IMPT) could further improve the dosimetric results allowed by IMRT. PATIENTS AND METHODS: We re-planned 7 MPM cases using both photons and protons, by carrying out IMRT and IMPT plans. For both techniques, conventional dose comparisons and normal tissue complication probability (NTCP) analysis were performed. In 3 cases, additional IMPT plans were generated with different beam dimensions. RESULTS: IMPT allowed a slight improvement in target coverage and clear advantages in dose conformity (p < 0.001) and dose homogeneity (p = 0.01). Better organ at risk (OAR) sparing was obtained with IMPT, in particular for the liver (D(mean) reduction of 9.5 Gy, p = 0.001) and ipsilateral kidney (V(20) reduction of 58%, p = 0.001), together with a very large reduction of mean dose for the contralateral lung (0.2 Gy vs 6.1 Gy, p = 0.0001). NTCP values for the liver showed a systematic superiority of IMPT with respect to IMRT for both the esophagus (average NTCP 14% vs. 30.5%) and the ipsilateral kidney (p = 0.001). Concerning plans obtained with different spot dimensions, a slight loss of target coverage was observed along with sigma increase, while maintaining OAR irradiation always under planning constraints. CONCLUSION: Results suggest that IMPT allows better OAR sparing with respect to IMRT, mainly for the liver, ipsilateral kidney, and contralateral lung. The use of a spot dimension larger than 3 * 3 mm (up to 9 * 9 mm) does not compromise dosimetric results and allows a shorter delivery time. PMID- 22318327 TI - Radiotherapy in elderly patients with inoperable esophageal cancer. Is there a benefit? AB - BACKGROUND: Radiation oncologists increasingly face elderly cancer patients impaired by comorbidities and reduced performance status. As less data are available for this particular group of patients, the aim of the study was to assess the prognosis of inoperable esophageal cancer patients >= 70 years undergoing definitive radiotherapy or radiochemotherapy. PATIENTS AND TREATMENT PROTOCOL: Patients aged >= 70 with inoperable carcinoma of the esophagus undergoing definitive radio(chemo)therapy between 1995 and 2006 at the University of Cologne were included retrospectively. Maximal total dose of radiotherapy administered was 63 Gy (5 * 1.8 Gy/week). Chemotherapy consisted of cisplatin (20 mg/m(2) on days 1-5 and days 29-33) and 5-fluorouracil (650-1,000 mg/m(2) on days 1-5 and days 29-33). Efficacy was compared with a cohort of 152 patients < 70 years treated with the same protocol during the same time period. RESULTS: A total of 51 patients aged >= 70 with inoperable cancer of the esophagus undergoing definitive therapy were identified (stage I/II 23.5%, stage III 56.9%, stage IV 9.8%; squamous cell carcinoma 74.5%, adenocarcinoma 25.5%). While 15 patients (29.4%) received combined radiochemotherapy (RCT), 40 patients (70.6%) were treated with radiotherapy alone (RT). Median progression-free survival (PFS) was 9.5 months; median overall survival (OS) was 13.9 months. Patients treated with RCT had a 2-year OS rate of 53.3% compared with 16.7% for RT patients (p = 0.039). The 2-year OS for clinically lymph node negative patients was 38.5% compared with 21.2% for lymph node positive patients (p = 0.072). Median OS was not significantly different between patients >= 70 years versus the patient cohort (n = 152) aged < 70 years (13.9 vs. 7.2 months, p = 0.072) but PFS showed a significant difference (4.9 vs. 9.5 months, p = 0.026) in favor of the > 70 years group. CONCLUSION: Prognosis in elderly patients with inoperable esophageal cancer undergoing definitive radiotherapy/radiochemotherapy is limited, although it is not inferior to patients < 70 years. PMID- 22318328 TI - Re-irradiation combined with capecitabine in locally recurrent squamous cell carcinoma of the head and neck. A prospective phase II trial. AB - BACKGROUND: We performed a prospective phase II trial to investigate the safety and efficacy of radiotherapy combined with capecitabine in patients suffering from a recurrence of a squamous cell carcinoma of the head and neck (SCCHN) within a previously irradiated field. PATIENTS AND METHODS: A total of 31 evaluable patients with recurrent SCCHN received re-irradiation with a total dose of 50 Gy (25 fractions over 5 weeks) up to a maximum of 60 Gy combined with 900 mg/m(2)/day capecitabine given on the days of radiotherapy. RESULTS: The median time to relapse after the first course of radiotherapy was 15 months. The overall response rate in our study was 68% including 6 patients with a complete response. The median overall survival was 8.4 months. Grade 3 or 4 mucositis occurred in 4 patients and 1 patient, respectively. No grade 4 hematological toxicities were observed; 1 patient had grade 3 anemia. The cumulative median lifetime dose was 116 Gy. CONCLUSION: Capecitabine combined with re-irradiation is a well-tolerated treatment in patients with recurrent SCCHN. In light of its good tolerability, it appears to be a potential option for patients with a reduced performance status and may also serve as a basis for novel treatment concepts, such as in combination with targeted therapies. PMID- 22318329 TI - Risk factors related to interfractional variation in whole pelvic irradiation for locally advanced pelvic malignancies. AB - PURPOSE: The goal of the present study was to demonstrate risk factors affecting the interfractional variation in whole pelvic irradiation. PATIENTS AND METHODS: Daily image acquisitions of 101 patients with locally advanced pelvic malignancy were undertaken using a kilo-voltage orthogonal on-board imager. The baseline deviation (the shift between the initial treatment and each fraction; Value(Base)) and day-to-day variation (the shift between the previous treatment and each fraction; Value(DD)) were measured. The standard deviations (SD) along the x- (right-left), y- (cranial-caudal), and z- (anterior-posterior) axes (SD[x], SD[y], and SD[z], respectively), the 3D vector of the SD (SD[3D]), and the mean of 3D shift (mean[3D]) were calculated in each patient. Various clinical factors, lumbar pelvic balance and rotation, and the shift of 5 consecutive fractions from the initial treatment (Value(5Fx)) were investigated as risk factors. RESULTS: The prone set-up showed a larger mean(Base)[3D] than in the supine position (p =0 .063). A body mass index (BMI) >= 30 kg/m(2) resulted in the largest mean(DD)[3D] (p = 0.078) and SD(DD)[3D] (p = 0.058). All the SD(5Fx) along the x-, y-, and z-axes had moderate linear relationships with SD(Base) and SD(DD) (p < 0.001). The SD(5Fx)[3D] also had a moderate linear relationship with the mean(Base)[3D], mean(DD)[3D], SD(Base)[3D], and SD(DD)[3D] (p < 0.001). In multivariate analysis, the SD(5Fx) had the same significant relationship with SD(Base) and SD(DD) (p < 0.001). A BMI >= 30 kg/m(2) was associated with the largest SD(DD)[x] (p = 0.003). CONCLUSION: Close surveillance through high quality and frequent image guidance is recommended for patients with extensive variations of the initial five consecutive fractions or obesity. PMID- 22318330 TI - Basal HIF-1alpha expression levels are not predictive for radiosensitivity of human cancer cell lines. AB - BACKGROUND AND PURPOSE: High levels of hypoxia inducible factor (HIF)-1alpha in tumors are reported to be associated with tumor progression and resistance to therapy. To examine the impact of HIF-1alpha on radioresistance under normoxia, the sensitivity towards irradiation was measured in human tumor cell lines that differ significantly in their basal HIF-1alpha levels. MATERIAL AND METHODS: HIF 1alpha levels were quantified in lysates of H1339, EPLC-272H, A549, SAS, XF354, FaDu, BHY, and CX- tumor cell lines by ELISA. Protein levels of HIF-1alpha, HIF 2alpha, carbonic anhydrase IX (CA IX), and GAPDH were assessed by Western blot analysis. Knock-down experiments were performed using HIF-1alpha siRNA. Clonogenic survival after irradiation was determined by the colony forming assay. RESULTS: According to their basal HIF-1alpha status, the tumor cell lines were divided into low (SAS, XF354, FaDu, A549, CX-), intermediate (EPLC-272H, BHY), and high (H1339) HIF-1alpha expressors. The functionality of the high basal HIF 1alpha expression in H1339 cells was proven by reduced CA IX expression after knocking-down HIF-1alpha. Linear regression analysis revealed no correlation between basal HIF-1alpha levels and the survival fraction at either 2 or 4 Gy in all tumor cell lines investigated. CONCLUSION: Our data suggest that basal HIF 1alpha levels in human tumor cell lines do not predict their radiosensitivity under normoxia. PMID- 22318331 TI - Concerning the final report "Hyperthermia: a systematic review" of the Ludwig Boltzmann Institute for Health Technology Assessment, Vienna, March 2010. PMID- 22318332 TI - Deletion of gene encoding methyltransferase (gidB) confers high-level antimicrobial resistance in Salmonella. AB - The glucose-inhibited division gene (gid)B, which resides in the gid operon, was thought to have a role in the modulation of genes similar to that of gidA. Recent studies have indicated that GidB is a methyltransferase enzyme that is involved in the methylation of the 16S ribosomal RNA (rRNA) in Escherichia coli. In this study, we investigated the role of GidB in susceptibility to antibiotics and the overall biology of Salmonella. A gidB isogenic mutant of Salmonella was constructed and subsequently characterized under different conditions. Our data indicated that growth and invasion characteristics of the gidB mutant were similar to those of the wild type (WT). The gidB mutant was outgrown by the WT in a competitive growth assay, indicating a compromised overall bacterial fitness. Under the stress of nalidixic acid, the gidB mutant's motility was significantly reduced. Similarly, the mutant showed a filamentous morphology and smaller colony size compared with the rod-shaped and large colonies of the WT in the presence of nalidixic acid. Most importantly, deletion of gidB conferred high-level resistance to the aminoglycoside antibiotics streptomycin and neomycin. A primer extension assay determined the methylation site for the WT to be at G527 of the 16S rRNA. A lack of methylation in the mutant indicated that GidB is required for this methylation. Taken together, these data indicate that the GidB enzyme has a significant role in the alteration of antibiotic susceptibility and the modulation of growth and morphology under stress conditions in Salmonella. PMID- 22318333 TI - Synthesis and properties of a novel brominated oligomycin A derivative. PMID- 22318334 TI - Benzomalvin E, an indoleamine 2,3-dioxygenase inhibitor isolated from Penicillium sp. FN070315. PMID- 22318335 TI - Radiographic remodeling of the shoulder joint in a patient with rheumatoid arthritis after 4 years of treatment with etanercept. PMID- 22318336 TI - Herpesviruses enhance fibrin clot lysis. AB - The incorporation of virus- and host-derived procoagulant factors initiates clotting directly on the surface of herpesviruses, which is an explanation for their correlation to vascular disease. The virus exploits the resulting thrombin to enhance infection by modulating the host cell through protease activated receptor (PAR) 1 signalling. Prior reports demonstrated that at least one herpesvirus expresses surface annexin A2 (A2), a cofactor for tissue plasminogen activator (tPA)-dependent activation of plasminogen to plasmin. Since plasmin is both a fibrinolytic protease and PAR agonist, we investigated whether herpesviruses enhance fibrinolysis and the effect of plasmin on cell infection. Herpes simplex virus types 1 (HSV1) and 2, and cytomegalovirus (CMV) purified from various cell lines each accelerated the proteolytic activation of plasminogen to plasmin by tPA. Ligand blots identified A2 as one of several plasminogen binding partners associated with the virus when compared to an A2 deficient virus. This was confirmed with inhibitory A2-antibodies. However, A2 was not required for virus-enhanced plasmin generation. HSV1, HSV2 and CMV accelerated tPA-dependent fibrin clot lysis by up to 2.8-fold. Modest plasmin generation and fibrinolysis was detected independent of exogenous tPA, which was inhibited by plasminogen activator inhibitor type-1 and epsilon-aminocaproic acid; however, the molecular basis remains speculative. Up to a ~6-fold enhancement of infection was provided by plasmin-mediated cell infection. Inhibitory antibodies revealed that plasmin increased HSV1 infection through a mechanism involving PAR2. Thus, virus-enhanced fibrinolysis may help explain the paradox of the highly procoagulant in vitro herpesvirus surface eliciting only relatively weak independent vascular disease risk. PMID- 22318337 TI - Abnormal bihemispheric responses in schizophrenia patients following cathodal transcranial direct stimulation. AB - Post-mortem and in vivo studies provide evidence for a link between reduced plasticity and dysconnectivity in schizophrenia patients. It has been suggested that the association between plasticity and connectivity contributes to the pathophysiology and symptomatology of schizophrenia. However, little is known about the impact of glutamate-dependent long-term depression (LTD)-like cortical plasticity on inter-hemispheric connectivity in schizophrenia patients. The aim of the present study was to investigate LTD-like cortical plasticity following excitability-diminishing cathodal transcranial direct current stimulation (tDCS) of the left primary motor cortex (M1) and its effects on the non-stimulated right M1. Eighteen schizophrenia patients and 18 matched (age, gender, handedness, and smoking status) control subjects were investigated in this study. Corticospinal excitability changes following tDCS and intra-cortical inhibitory circuits were monitored with transcranial magnetic stimulation. On the stimulated hemisphere, cathodal tDCS increased resting motor thresholds (RMT) in both groups and decreased motor-evoked potential (MEP) sizes in healthy controls to a greater extent compared to schizophrenia patients. On the non-stimulated hemisphere, RMTs were increased and MEPs were decreased only in the healthy control group. Our results confirm previous findings of reduced LTD-like plasticity in schizophrenia patients and offer hypothetical and indirect in vivo evidence for an association between LTD-like cortical plasticity and inter-hemispheric connectivity in schizophrenia patients. Moreover, our findings highlight the impact of plasticity on connectivity. Dysfunctional N-methyl D-aspartate receptors or modulation of dopaminergic transmission can explain these findings. Nevertheless, the effects of antipsychotic medication still need to be considered. PMID- 22318339 TI - Synthesis of graphene film from fullerene rods. AB - Here we demonstrate a facile approach to grow uniform and large area single layer graphene directly over polycrystalline metal foil from fullerene, where fullerene molecules formed rod-like polycrystals in the toluene solvent. The generated pressure on sandwich structures has enhanced the density (scalable) as well as quality of graphene at partially low temperatures. PMID- 22318340 TI - Predictive value of endoscopic findings in the diagnosis of active intestinal amebiasis. AB - Endoscopic diagnosis of amebic colitis can be difficult because its appearance may mimic other forms of colonic disease. The aim of this study was to identify predictive endoscopic findings for amebic colitis. Patients with suspected amebic colitis based on distinctive endoscopic findings such as aphthae or erosions, ulcers, exudates, or a bump, were included in the study. A total of 157 patients were selected, 50 of whom had amebic colitis. The sensitivity and specificity of endoscopic findings that were significantly associated with amebic colitis were: cecal lesions (80% and 54%), multiple number of lesions (96% and 29%), presence of aphthae or erosions (84% and 37%), and presence of exudate (88% and 74%). Multivariate analysis revealed that the best combination of findings to predict amebic colitis was the presence of cecal lesions, multiple lesions, and exudates, which corresponded to an area under the receiver operating characteristic curve of 0.89 (95% confidence interval 0.82-0.95). PMID- 22318342 TI - Functional porphyrinic metal-organic frameworks: crystal engineering and applications. AB - Metal-organic frameworks (MOFs) are a kind of material which are able to integrate functional groups on their framework backbones. The tunable functionalities let MOFs be applied in various fields of luminescence, gas storage, sensing, magnetics, catalysis and biomedical imaging. Because of their interesting properties of structural robustness, catalysis, charge and energy transformations, using porphyrins and metalloporphyrins as synthons for the fabrication of functional MOFs has attracted considerable interest. Many efficient strategies have been established for the construction of functional porphyrinic MOFs, and some of them present interesting properties for potential applications. This perspective is aimed to summarize recent progress on porphyrinic MOFs, including new synthesis strategies and applications. PMID- 22318341 TI - Neuroprotective properties of Loranthus parasiticus aqueous fraction against oxidative stress-induced damage in NG108-15 cells. AB - Loranthus parasiticus, a Chinese folk medicine, has been widely used for the treatment of brain diseases, particularly in southwest China. Hence, the present neuroprotection model was designed to investigate its neuroprotective properties against H(2)O(2)-induced oxidative stress in NG108-15 cells. L. parasiticus aqueous fraction (LPAF), which was selected in the present study, had proved to be the most active fraction among the other tested extracts and fractions in our previous screening. The restoration of depleted intracellular glutathione (GSH), a major endogenous antioxidant, by LPAF was observed after H(2)O(2) insult. Pretreatment with LPAF substantially reduced the production of intracellular reactive oxygen species generated from H(2)O(2). Apoptotic features such as externalization of phosphatidylserine and disruption of mitochondrial membrane potential were significantly attenuated by LPAF. In addition, cell cycle analysis revealed a prominent decrease in the H(2)O(2)-induced sub-G(1) population by LPAF. Moreover, apoptotic morphological analysis by DAPI nuclear staining demonstrated that NG108-15 cells treated with H(2)O(2) exhibited apoptotic features, while such changes were greatly reduced in cells pretreated with LPAF. Taken together, these findings confirmed that LPAF exerts marked neuroprotective activity, which raises the possibility of potential therapeutic application of LPAF for managing oxidative stress-related neurological disorders and supports the traditional use of L. parasiticus in treating brain-related diseases. PMID- 22318343 TI - Redox-dependent conformational changes in eukaryotic cytochromes revealed by paramagnetic NMR spectroscopy. AB - Cytochrome c (Cc) is a soluble electron carrier protein, transferring reducing equivalents between Cc reductase and Cc oxidase in eukaryotes. In this work, we assessed the structural differences between reduced and oxidized Cc in solution by paramagnetic NMR spectroscopy. First, we have obtained nearly-complete backbone NMR resonance assignments for iso-1-yeast Cc and horse Cc in both oxidation states. These were further used to derive pseudocontact shifts (PCSs) arising from the paramagnetic haem group. Then, an extensive dataset comprising over 450 measured PCSs and high-resolution X-ray and solution NMR structures of both proteins were used to define the anisotropic magnetic susceptibility tensor, Deltachi. For most nuclei, the PCSs back-calculated from the Deltachi tensor are in excellent agreement with the experimental PCS values. However, several contiguous stretches-clustered around G41, N52, and A81-exhibit large deviations both in yeast and horse Cc. This behaviour is indicative of redox-dependent structural changes, the extent of which is likely conserved in the protein family. We propose that the observed discrepancies arise from the changes in protein dynamics and discuss possible functional implications. PMID- 22318344 TI - Bilateral anterior dislocation of the shoulders at the start of a backstroke competition. AB - Bilateral anterior dislocation of the shoulders is very rare. A 20-year-old man presented with bilateral anterior shoulder dislocation as a result of a diving incident. He complained of pain and restriction of movement in both shoulders with abducted and externally rotated arms. Radiographs revealed that the shoulders were dislocated. The patient was treated with closed reduction and was able to resume swimming 3 months later. To our knowledge, this is the first bilateral anterior dislocation of the shoulders during a backstroke swimming competition that was caused by this mechanism of injury. The rarity of this lesion and its uncommon mechanism prompted us to relate this observation. PMID- 22318345 TI - A genome-wide association study identifies SNP in DCC is associated with gallbladder cancer in the Japanese population. AB - Gallbladder cancer (GC) is a relatively uncommon cancer with higher incidence in certain areas including Japan. Because of the difficulty in diagnosis, prognosis of GC is very poor. To identify genetic determinants of GC, we conducted a genome wide association study (GWAS) in 41 GC patients and 866 controls. Association between each single-nucleotide polymorphism (SNP) with GC susceptibility was evaluated by multivariate logistic regression analysis conditioned on age and gender of subjects. SNPs that showed suggestive association (P<1 * 10(-4)) with GC were further examined in 30 cases and 898 controls. SNP rs7504990 in the DCC (deleted in colorectal cancer, 18q21.3) that encodes a netrin 1 receptor achieved a combined P-value of 7.46 * 10(-8) (OR=6.95; 95% CI=3.43-14.08). Subsequent imputation analysis identified multiple SNPs with similarly strong associations in an adjacent genomic region, where loss of heterozygosity was reported in GC and other cancers. Reduced expression of DCC was indicated to be associated with the poorly differentiated histological type, increased proliferation and metastasis through loss of adhesiveness. However, due to the limited sample size investigated here, further replication study and functional analysis would be necessary to further confirm the result of the association. PMID- 22318346 TI - Prevalence of inositol 1, 4, 5-triphosphate receptor type 1 gene deletion, the mutation for spinocerebellar ataxia type 15, in Japan screened by gene dosage. AB - Spinocerebellar ataxia type 15 (SCA15) is an autosomal dominant neurodegenerative disorder clinically characterized by late-onset, slowly progressive pure cerebellar ataxia. This disease is caused by a heterozygous deletion of the inositol 1, 4, 5-triphosphate receptor type 1 (ITPR1) gene, suggesting that haploinsufficiency of the receptor function is the plausible disease mechanism. To clarify the prevalence of SCA15 in Japan, we designed four sets of probes and primers in different regions of ITPR1 and performed TaqMan PCR assay to search for gene deletions in 226 index SCA patients excluded for repeat expansion disorders. Deletion was found in only one patient, in whom gait ataxia started at 51 years of age and progressed to show cerebellar ataxia. This study demonstrates a simple but efficient method for screening ITPR1 deletion. We also conclude that ITPR1 gene deletions are much rare in Japan than in Europe, comprising only 0.3% in all SCAs in Japan. PMID- 22318347 TI - On the trail of EHEC/EAEC--unraveling the gene regulatory networks of human pathogenic Escherichia coli bacteria. AB - Pathogenic Escherichia coli, such as Enterohemorrhagic E. coli (EHEC) and Enteroaggregative E. coli (EAEC), are globally widespread bacteria. Some may cause the hemolytic uremic syndrome (HUS). Varying strains cause epidemics all over the world. Recently, we observed an epidemic outbreak of a multi-resistant EHEC strain in Western Europe, mainly in Germany. The Robert Koch Institute reports >4300 infections and >50 deaths (July, 2011). Farmers lost several million EUR since the origin of infection was unclear. Here, we contribute to the currently ongoing research with a computer-aided study of EHEC transcriptional regulatory interactions, a network of genetic switches that control, for instance, pathogenicity, survival and reproduction of bacterial cells. Our strategy is to utilize knowledge of gene regulatory networks from the evolutionary relative E. coli K-12, a harmless strain mainly used for wet lab studies. In order to provide high-potential candidates for human pathogenic E. coli bacteria, such as EHEC, we developed the integrated online database and an analysis platform EhecRegNet. We utilize 3489 known regulations from E. coli K-12 for predictions of yet unknown gene regulatory interactions in 16 human pathogens. For these strains we predict 40,913 regulatory interactions. EhecRegNet is based on the identification of evolutionarily conserved regulatory sites within the DNA of the harmless E. coli K-12 and the pathogens. Identifying and characterizing EHEC's genetic control mechanism network on a large scale will allow for a better understanding of its survival and infection strategies. This will support the development of urgently needed new treatments. EhecRegNet is online via http://www.ehecregnet.de. PMID- 22318348 TI - Expression of interleukin-18 in a rat model of deep vein thrombosis. AB - AIM: Interleukin-18 (IL-18) is an important proinflammatory cytokine. However, little is known about the roles of IL-18 in the process of venous thrombosis. This study aimed to investigate the roles of IL-18 during deep vein thrombosis (DVT). METHODS: Fifty rats were randomly divided into 0 (control group), 12, 24, 36 and 48 h groups (10 rats in each group) by observation time. The inferior vena cava (IVC) was ligated to establish the DVT model. Serum samples were extracted to determine the levels of IL-18, tumor necrosis factor-alpha (TNF-alpha), thromboxane B2 (TXB2) and 6-keto-prostaglandin Fl alpha (6-keto-PG Flalpha) by enzyme-linked immunosorbent assay (ELISA). The weight and length of IVC was also measured. RESULTS: The DVT model was successfully established by ligating IVC. The injury of vein endothelium was observed in the model groups. IL-18, TNF alpha, TXB2, TXB2/6-keto-PG Flalpha levels and thrombus weight were significantly increased in the model groups as compared with the control group, and peaked at 24 h after IVC ligation. 6-keto-PG F1alpha slightly decreased in the model groups comparing with the control group. IL-18 was positively correlated with TNF-alpha, TXB2, TXB2/6-keto-PG Flalpha ratio and thrombus weight. However, IL-18 was negatively correlated with 6-keto-PG Flalpha. There was a positive correlation between TXB2/6-keto-PG Flalpha ratio and thrombus weight. CONCLUSION: Serum IL-18 level increased in the process of DVT, which might impair venous endothelial cells and result in venous thrombosis. IL-18 might be a new potential therapeutic target of DVT prevention. PMID- 22318349 TI - Relationships between climate, productivity and vegetation in southern Mongolian drylands. AB - We assessed the relationship between open-source data on net primary production and precipitation for the southern Mongolian Gobi, and related this information to data obtained from a set of 1418 vegetation releves sampled in the region. Gradients determining plant community diversity and composition were examined, and the relation between alpha-diversity and key environmental parameters was tested.The correlation between net primary production and precipitation within our working area was fairly high (r(2) = 0.66). The variance of the net primary production was related to the average annual precipitation; at sites with more than ~220 mm/a precipitation the median coefficient of variation in productivity data decreased, indicating a rather gradual shift from a non-equilibrium ecosystem towards an equilibrium ecosystem with increasing moisture. A DCA ordination showed that the main gradient in plant community composition was closely correlated to environmental variables for altitude, precipitation and net primary production. All three parameters were also significant predictors of the species diversity. The final model, which included an additional quadratic term for longitude, predicted local plant biodiversity at r(2) = 0.57.The results can be directly applied to both resource management and nature conservation within the area. For future studies a closer focus on the characterisation of non equilibrium rangelands based on modelled productivity layers is suggested. PMID- 22318350 TI - Value of diffusion-weighted images in differentiating mid-course responders to chemotherapy for osteosarcoma compared to the histological response: preliminary results. AB - BACKGROUND: Preoperative diffusion-weighted MRI (DW-MRI) has been described as an efficient method to differentiate good and poor responders to chemotherapy in osteosarcoma patients. A DW-MRI performed earlier during treatment could be helpful in monitoring chemotherapy. OBJECTIVE: To assess the accuracy of DW-MRI in evaluating response to chemotherapy in the treatment of osteosarcoma, more specifically at mid-course of treatment. MATERIALS AND METHODS: This study was carried out on a prospective series of adolescents treated for long-bone osteosarcoma. MR examinations were performed at diagnosis (MRI-1), at mid-course of chemotherapy (MRI-2), and immediately before surgery (MRI-3). A DW sequence was performed using diffusion gradients of b0 and b900. The apparent diffusion coefficients (ADC1, ADC2, ADC3, respectively), their differentials (ADC2 - ADC1 and ADC3 - ADC1), and their variation (ADC2 - ADC1/ADC1 and ADC3 - ADC1/ADC1) were calculated for each of these three time points. RESULTS: Fifteen patients were included. Patients with no increase in ADC showed a poor response to chemotherapy on their histology results. At mid-course, the three calculated values were significantly different between good and poor responders. ADC2 - ADC1 enabled us to detect, with 100% specificity, four out of seven of the poor responders. There was no significant difference in the values at MRI-3 between the two groups. CONCLUSION: DW-MRI performed both at baseline and mid-course of neoadjuvant chemotherapy is an efficient method to predict further histological response of osteosarcoma. This method could be used as an early prognostic factor to monitor preoperative chemotherapy. PMID- 22318351 TI - Biosimilar rhG-CSFs: how similar are they? AB - Biosimilars are more affordable copycat versions of originator biological products in much the same way as generics are copies of small molecule pharmaceuticals. However, while generics are approved on the basis of structural and pharmacokinetic equivalence, the intricate structure of biological medicinal products and the complex nature of their manufacturing process in living organisms impose a separate, and more stringent, regulatory approval process. The aims of this article are (a) to discuss key aspects of the development process and authorization requirements for biosimilars in Europe using published comparative physicochemical and clinical data for EU-approved recombinant human granulocyte colony stimulating factor (rhG-CSF) biosimilars, the most recent addition to the therapeutic category of hematopoietic growth factors, and (b) to demonstrate that the rigorous scientific evaluation process is designed to ensure that their clinical safety and efficacy is not compromised by the abbreviated development program. PMID- 22318352 TI - [Regional and social disparities in tobacco use in the 2009 Microcensus: results in the population of North Rhine-Westphalia and its communities]. AB - INTRODUCTION: Tobacco smoking is the single greatest cause of avoidable morbidity and mortality. The official Microcensus is one of the most important sources of systematic reporting about smoking in Germany. METHODS: The selection rate of the random sample survey was 1% of the population in the 2009 Microcensus in North Rhine-Westphalia. Most of the information was given under statutory obligations. Providing health information in the health supplementary programme was optional with response of about four-fifths of the interviewees. RESULTS: According to the 2009 Microcensus regional file, 37% of the men and 28% of the women of employable age (15-64 years) are smokers in North Rhine-Westphalia (N=9 219 thousand). Tobacco smoking prevalence is associated with influencing social factors. The probability of current smoking rises with the decrease of the socioeconomic status and the level of education. Job-seekers have a significantly elevated odds ratio for smoking, the chance of quitting smoking is minimised. The analyses show that the percentages of smokers and ex-smokers varied widely between the communities in North Rhine-Westphalia. The prevalence of current tobacco smoking increases highly in the communities with rates of inhabitants who receive government financial aid or unemployment benefits to secure their basic livelihood. CONCLUSION: The Microcensus reveals distinct disparities in adult smoking prevalence between the regions and additionally strong social disparities in adult smoking prevalence. The nicotine addiction accelerates health inequalities. The Microcensus may have potential for monitoring tobacco use in Germany and in the regions and communities and for evaluating the effectiveness of tobacco control programmes over time. The Microcensus analyses can be used for the development of primary and secondary tobacco prevention strategies. PMID- 22318353 TI - Secondary acute myeloid leukemia occurring after successful treatment of acute promyelocytic leukemia. PMID- 22318354 TI - Clinical impact and predictors of carotid artery in-stent restenosis. AB - To assess the incidence and clinical significance as well as predictors of in stent restenosis (ISR) after carotid artery stenting (CAS) diagnosed with serial duplex sonography investigations. We analyzed 215 CAS procedures that had clinical and serial carotid duplex ultrasound investigations. The incidence of in stent restenosis (ISR) and periprocedural as well as long-term clinical complications were recorded. The influence of an ISR on clinical complication was analyzed using Kaplan-Meier curves and clinical risk factors for the development of an ISR with multivariate logistic regression. During a median follow-up time of 33.4 months (interquartile range 15.3-53.7) an ISR of >=70% was detected in 12 (6.1%) of 215 arteries (mean age of 68.1 +/- 9.8 years, 71.6% male). The combined stroke and death rate during long-term follow-up was significantly higher in the group with an ISR [odds ratio (OR): 3.59, 95% confidence interval (CI): 1.50 8.59, p = 0.004]. After applying multivariate logistic regression analysis contralateral carotid occlusion (OR 10.11, 95% CI 2.06-49.63, p = 0.004), carotid endarterectomy (CEA) restenosis (OR 8.87, 95% CI 1.68-46.84, p = 0.010) and postprocedural carotid duplex ultrasound with a PSV >=120 cm/s (OR 6.33, 95% CI 1.27-31.44, p = 0.024) were independent predictors of ISR. ISR after CAS during long-term follow-up is associated with a higher proportion of clinical complications. A close follow-up is suggested especially in those patients with the aforementioned independent predictors of an ISR. Against the background of a lacking established treatment of ISR, these findings should be taken into account when offering CAS as a treatment alternative to CEA. PMID- 22318355 TI - Focal CT hypoperfusion in HaNDL. PMID- 22318356 TI - 3-Bromopyruvate antagonizes effects of lactate and pyruvate, synergizes with citrate and exerts novel anti-glioma effects. AB - Oxidative stress-energy depletion therapy using oxidative stress induced by D amino acid oxidase (DAO) and energy depletion induced by 3-bromopyruvate (3BP) was reported recently (El Sayed et al., Cancer Gene Ther., 19, 1-18, 2012). Even in the presence of oxygen, cancer cells oxidize glucose preferentially to produce lactate (Warburg effect) which seems vital for cancer microenvironment and progression. 3BP is a closely related structure to lactate and pyruvate and may antagonize their effects as a novel mechanism of its action. Pyruvate exerted a potent H(2)O(2) scavenging effect to exogenous H(2)O(2), while lactate had no scavenging effect. 3BP induced H(2)O(2) production. Pyruvate protected against H(2)O(2)-induced C6 glioma cell death, 3BP-induced C6 glioma cell death but not against DAO/D-serine-induced cell death, while lactate had no protecting effect. Lactate and pyruvate protected against 3BP-induced C6 glioma cell death and energy depletion which were overcome with higher doses of 3BP. Lactate and pyruvate enhanced migratory power of C6 glioma which was blocked by 3BP. Pyruvate and lactate did not protect against C6 glioma cell death induced by other glycolytic inhibitors e.g. citrate (inhibitor of phosphofructokinase) and sodium fluoride (inhibitor of enolase). Serial doses of 3BP were synergistic with citrate in decreasing viability of C6 glioma cells and spheroids. Glycolysis subjected to double inhibition using 3BP with citrate depleted ATP, clonogenic power and migratory power of C6 glioma cells. 3BP induced a caspase-dependent cell death in C6 glioma. 3BP was powerful in decreasing viability of human glioblastoma multiforme cells (U373MG) and C6 glioma in a dose- and time dependent manner. PMID- 22318357 TI - Bromopyruvate mediates autophagy and cardiolipin degradation to monolyso cardiolipin in GL15 glioblastoma cells. AB - The GL15 glioblastoma cell line undergoes viability loss upon treatment with bromopyruvate. The biochemical mechanisms triggered by the antiglycolytic agent indicate the activation of an autophagic pathway. Acridine orange stains acidic intracellular vesicles already 60 min after bromopyruvate treatment, whereas autophagosomes engulfing electron dense material are well evidenced 18 h later. The autophagic process is accompanied by the expression of the early autophagosomal marker Atg5 and by LC3-II formation, a late biochemical marker associated with autophagosomes. In agreement with the autophagic route activation, the inhibitory and the activator Akt and ERK signaling pathways are depressed and enhanced, respectively. In spite of the energetic collapse suffered by bromopyruvate-treated cells, MALDI-TOF mass spectrometry lipid analysis does not evidence a decrease of the major phospholipids, in accordance with the need of phospholipids for autophagosomal membranes biogenesis. Contrarily, mitochondrial cardiolipin decreases, accompanied by monolyso-cardiolipin formation and complete cytochrome c degradation, events that could target mitochondria to autophagy. However, in our experimental conditions cytochrome c degradation seems to be independent of the autophagic process. PMID- 22318358 TI - Flow cytometric evaluation of the effects of 3-bromopyruvate (3BP) and dichloracetate (DCA) on THP-1 cells: a multiparameter analysis. AB - Two human leukemia cells K562 and THP-1, the breast cancer lines MCF-7 and ZR-75 1, and the melanoma line MDA-MB-435S were compared by flowcytometry for their behaviour at increasing levels of 3BP. K562 and THP-1 responded to 3BP by membrane depolarization and increased ROS; MCF-7 and ZR-75-1 showed decreased polarization and low ROS increase; MDA-MB-435S had limited depolarization and no ROS increase. THP-1 cells exposed to a range of 3BP concentrations in combination with DCA showed increase of polarization, slight ROS increase, and weakened nuclear integrity. 3BP and DCA show no synergism, but have complementary destructive effects on THP-1 cells. The data led to the conclusion that the THP-1 cells do not carry a functional membrane monocarboxylate transporter (MCT) or that 3BP circumvents MCT binding and can enter these cells independently. PMID- 22318359 TI - ATAD3, a vital membrane bound mitochondrial ATPase involved in tumor progression. AB - ATAD3 (ATPase family AAA Domain-containing protein 3) is a mitochondrial membrane bound ATPase whose function has not yet been discovered but its role is essential for embryonic development. The ATAD3 gene has existed since the pluri-cellular organisms with specialized tissues and has remained unique until vertebrates. In primates and human, two other genes have appeared (called ATAD3B and ATAD3C versus ATAD3A the ancestral gene). ATAD3 knock-down in different non-transformed cell lines is associated with drastic changes in the mitochondrial network, inhibition of proliferation and modification of the functional interactions between mitochondria and endoplasmic reticulum. However, the analysis of the cellular properties of ATAD3A and ATAD3B in different human cancer cell lines shows on the contrary that they can present anti-proliferative and chemoresistant properties. ATAD3 may therefore be implicated in an unknown but essential and growth-linked mitochondrial function existing since pluri-cellular organization and involved in tumorigenesis. PMID- 22318360 TI - [The effects of hormone replacement therapy on mind and brain]. AB - Hormonal fluctuations during the perimenopausal transition lead to physical discomfort but are also frequently accompanied by mood swings, depressive symptoms, anxiety and sleeping disorders. The important role of the neurotransmitter serotonin in the pathogenesis of anxiety disorders and major depression is unquestioned, but only little is known about the influence of sex hormones on the serotonergic system. This review provides an overview of potential risk factors for the occurrence of affective disorders in the menopausal transition and discusses possible therapeutic options. Current research findings from longitudinal studies testing the efficacy of hormone replacement therapy and antidepressants with effects on the serotonergic neurotransmission on physical and mental discomforts during menopause are presented. Furthermore, studies using positron emission tomography and genetic methods that explore the effects of sex steroids on different components of the serotonergic system are shown. The interactions between estrogen, progesterone and the serotonergic system are described, and possible neurobiological and endocrinological mechanisms underlying depressive symptoms in the perimenopause are elucidated. PMID- 22318361 TI - [Psychosocial integration of inpatients with borderline personality disorder: reflection of a health care system focused on symptom remission]. AB - BACKGROUND: Borderline personality disorder (BPD) is characterized by a profound instability of identity, by stress and affect dysregulation and impulsivity, and by cognitive-perceptual disturbances. These deficits seriously impair interpersonal experiences and social interaction. The typical impulsive style and psychosocial malfunctioning of these patients lead to grave disturbances in their everyday areas of life with numerous break-ups in all relevant areas of life and entail inadequate vocational placement. Despite vast demands on the health care system, BPD attracts little attention of care process research and reintegration measures as, for instance, exist for schizophrenia. At the LVR-Klinikum Dusseldorf as representative of a large clinic in North Rhein-Westphalia, we analysed socio-demographic characteristics of BPD inpatients. The aims of the study were to substantiate the high impact of the disease on patient's social and vocational integration and to sensitize for significant aspects of disease specific therapy and care. METHODS: A retrospective analysis of DGPPN-BADO of all patients (n = 9,425) who were admitted between January 2004 and December 2009 to the LVR-Klinikum Dusseldorf, department of psychiatry and psychotherapy, Heinrich Heine University Hospital, Germany. Data analysis involved the divisions general psychiatry and addictive disorders and covered 999 patients with BPD (ICD-10: F60.3) and 1,937 patients with schizophrenia (ICD-10: F20). The defined characteristics of DGPPN-BADO that depict psychosocial integration were "living situation at admission", "highest academic/professional degree achieved", "working situation" und "livelihood". Besides descriptive statistics of the elected variables, comparative analysis of the diagnoses BPD and schizophrenia involved calculating group differences after adjusting the groups for sex and age. Statistical analysis was performed by the chi2-test. RESULTS: The comparative analysis of psychosocially relevant BADO characteristics reveals a significantly stronger impairment of patients with BPD concerning their academic and professional qualification than patients with schizophrenia. Nevertheless they more often hold a job or cover their living expenses without subsidy, respectively. CONCLUSION: The data suggest a lack of general awareness in the significance of social and vocational disturbances in BPD. The interactional deficits of patients with BPD affect all areas of life but their illness-related nature seems to be disregarded in relevant life areas, such as educational processes and the vocational situation. Furthermore, the impact of BPD on earning capacity is not given adequate consideration in the assessment of pensions or subsidies. Consistent with the recent literature, our socio-demographic data indicate significant deficits of the present health system in handling BPD. PMID- 22318363 TI - Clinical application of prismatic lenses in the rehabilitation of neglect patients. A randomized controlled trial. AB - BACKGROUND: Many studies reveal that neglect is a major cause of disability in stroke patients, and two months from onset neglect is still present in approximately 50% of individuals with a right brain lesion. Among the various methods of neglect rehabilitation, we have turned our attention to the prism adaptation treatment, developed by Rossetti in 1998. This treatment uses prismatic lenses, which produce a deviation of the fixation point of the visual field of 10 degrees to the right, 5 degrees below the coordinates of reference resulting from neglect. AIM: To set out the possible effectiveness of less powerful lenses, we studied the response of a group of neglect patients treated with prismatic lenses that produce a deviation of the fixation point of only 5 degrees to the right, comparing them with a group of patients receiving placebo lenses. DESIGN: Randomized controlled trial. SETTING: Outpatients. POPULATION: The study involved 29 patients with left visual neglect. METHODS: All patients were assessed with a battery of seven visual-spatial tests. All patients were randomized by the pilot center and assigned to two different groups: "A" treated with pointing exercises and prismatic lenses of 5 degrees to the right; "B" treated with pointing exercises and neutral lenses. Each group was treated with 5 rehabilitation sessions, lasting about 30 minutes each, from Monday to Friday for one week in the morning, by the same investigator, in each center. CONCLUSION: The results showed that the prismatic lenses of only five degrees, used for the study, did not contribute to the variation in performance. Thus, this deviation of the fixation point of the visual field to the right is not sufficient to create a therapeutic effect. The improvement observed within the two groups, seems likely to be correlated with the pointing exercises, which force the subject to perform a visuomotor task with the healthy arm also in the neglected side. CLINICAL REHABILITATION IMPACT: We believe that in order to carry out an effective treatment with prismatic lenses they must have a grade of at least 20 prism diopters. Lower grades are unable to determine an effect. Finally, because of the severe impact of neglect on the work of the rehabilitation team, and since our data shows that only five sessions are sufficient to demonstrate a change in performance, we believe that it is appropriate to use this method, especially in the acute phase of the disease. PMID- 22318364 TI - A model for low dose effects of low-LET radiation delivered at high dose rates. AB - In vitro studies show that protective tumour-reducing effects occur for low dose rates (mGy per minute). To account for these phenomena, we have previously developed stochastic and deterministic multi-stage cancer models that include radiation-induced adaptations in DNA repair processes and radical scavenging. Here, these models are extended to account for the induction of radioprotective mechanisms for low doses of low LET radiation delivered at high dose rates. Cellular adaptations in DNA repair are related to temporal changes in the amount of DNA damage in a cell. The combined effects of endogenous DNA damage, background radiation and artificial irradiation are considered. PMID- 22318365 TI - Imagination and society: the role of visual sociology. AB - The paper presents the field of Visual Sociology as an approach that makes use of photographs, films, documentaries, videos, to capture and assess aspects of social life and social signals. It overviews some relevant works in the field, it deals with methodological and epistemological issues, by raising the question of the relation between the observer and the observed, and makes reference to some methods of analysis, such as those proposed by the Grounded Theory, and to some connected tools for automatic qualitative analysis, like NVivo. The relevance of visual sociology to the study of social signals lies in the fact that it can validly integrate the information, introducing a multi-modal approach in the analysis of social signals. PMID- 22318366 TI - MicroRNAs in the regulation of immune cell functions--implications for atherosclerotic vascular disease. AB - Regarded as a chronic inflammatory disease of the vessel wall, the development of atherosclerotic lesions is shaped by immune responses and their regulation. Macrophages and dendritic cells are positioned at the crossroad of innate and adaptive immune responses by sensing atherogenic danger signals and by taking up and presenting antigens. T helper cells and auto-antibodies produced by B cells, together with their cytokine responses in turn modulate atheroprogression. In addition, platelets contribute to atherosclerosis by multiple pathways. microRNAs (miRNAs) that post-transcriptionally regulate gene expression may thus critically control immune cell differentiation and functions during plaque evolution. This review summarises the role of miRNAs in regulating lipid uptake and expression of inflammatory mediators in monocytes/macrophages and dendritic cells, in lymphocyte functions with a focus on T helper cell responses, as well as in platelet biology, and the implications of altering these functions in vascular pathology and atherosclerosis. T systematically survey miRNA functions in controlling molecular mechanisms and immune responses in atherosclerosis holds potential for the development of novel miRNA-based strategies for therapies targeting inflammation and immunity in atherosclerosis. PMID- 22318367 TI - Reversible transient hydrogen storage in a fuel cell-supercapacitor hybrid device. AB - A new concept is investigated for hydrogen storage in a supercapacitor based on large-surface-area carbon material (Black Pearls 2000). Protons and electrons of hydrogen are separated on a fuel cell-type electrode and then stored separately in the electrical double layer, the electrons on the carbon and the protons in the aqueous electrolyte of the supercapacitor electrode. The merit of this concept is that it works spontaneously and reversibly near ambient pressure and temperature. This is in pronounced contrast to what has been known as electrochemical hydrogen storage, which does not involve hydrogen gas and where electrical work has to be spent in the loading process. With the present hybrid device, a H(2) storage capacity of 0.13 wt% was obtained, one order of magnitude more than what can be stored by conventional physisorption on large-surface-area carbons at the same pressure and temperature. Raising the pressure from 1.5 to 3.5 bar increased the capacity by less than 20%, indicating saturation. A capacitance of 11 MUF cm(-2), comparable with that of a commercial double layer supercapacitor, was found using H(2)SO(4) as electrolyte. The chemical energy of the stored H(2) is almost a factor of 3 larger than the electrical energy stored in the supercapacitor. Further developments of this concept relate to a hydrogen buffer integrated inside a proton exchange membrane fuel cell to be used in case of peak power demand. This serial setup takes advantage of the suggested novel concept of hydrogen storage. It is fundamentally different from previous ways of operating a conventional supercapacitor hooked up in parallel to a fuel cell. PMID- 22318368 TI - A microfluidic device for high throughput bacterial biofilm studies. AB - Bacteria are almost always found in ecological niches as matrix-encased, surface associated, multi-species communities known as biofilms. It is well established that soluble chemical signals produced by the bacteria influence the organization and structure of the biofilm; therefore, there is significant interest in understanding how different chemical signals are coordinately utilized for community development. Conventional methods for investigating biofilm formation such as macro-scale flow cells are low-throughput, require large volumes, and do not allow spatial and temporal control of biofilm community formation. Here, we describe the development of a PDMS-based two-layer microfluidic flow cell (MUFC) device for investigating bacterial biofilm formation and organization in response to different concentrations of soluble signals. The MUFC device contains eight separate microchambers for cultivating biofilms exposed to eight different concentrations of signals through a single diffusive mixing-based concentration gradient generator. The presence of pneumatic valves and a separate cell seeding port that is independent from gradient-mixing channels offers complete isolation of the biofilm microchamber from the gradient mixer, and also performs well under continuous, batch or semi-batch conditions. We demonstrate the utility of the MUFC by studying the effect of different concentrations of indole-like biofilm signals (7-hydroxyindole and isatin), either individually or in combination, on biofilm development of pathogenic E. coli. This model can be used for developing a fundamental understanding of events leading to bacterial attachment to surfaces that are important in infections and chemicals that influence the biofilm formation or inhibition. PMID- 22318369 TI - Altered expression of sialylated glycoproteins in breast cancer using hydrazide chemistry and mass spectrometry. AB - Sialylation is one of the altered protein glycosylations associated with cancer development. The sialoglycoproteins in cancer cells, however, largely remain unidentified because of the lack of a method for quantitative analysis of sialoglycoproteins. This manuscript presents a high throughput method for quantitative analysis of N-linked sialoglycoproteins using conditional hydrazide chemistry, liquid chromatography, and tandem mass spectrometry. We further applied the sialoglycoproteomic method to the profiling of breast cancer tissues and compared findings with the results from the total glycoproteomic analysis using the original hydrazide chemistry method. We identified altered expression of sialoglycoproteins, as well as the total glycoprotein changes associated with breast cancer. Using lectin and Western blot analysis, we characterized one of the sialoglycoproteins, versican, and confirmed that versican was most sialylated and elevated in breast cancer. Furthermore, we showed that versican was detected in both cancer epithelial cells and peritumoral stromal cells using immunohistochemistry. Tissue microarray analysis revealed that epithelial expression of versican had significant relations to lymph node metastasis and pathological stages. This is the first quantitative sialoglycoproteomic and glycoproteomic analysis of breast cancer and noncancerous tissues. These findings present a significant addition of the method to the identification of altered expression of sialylated glycoproteins associated with breast cancer development. PMID- 22318370 TI - msCompare: a framework for quantitative analysis of label-free LC-MS data for comparative candidate biomarker studies. AB - Data processing forms an integral part of biomarker discovery and contributes significantly to the ultimate result. To compare and evaluate various publicly available open source label-free data processing workflows, we developed msCompare, a modular framework that allows the arbitrary combination of different feature detection/quantification and alignment/matching algorithms in conjunction with a novel scoring method to evaluate their overall performance. We used msCompare to assess the performance of workflows built from modules of publicly available data processing packages such as SuperHirn, OpenMS, and MZmine and our in-house developed modules on peptide-spiked urine and trypsin-digested cerebrospinal fluid (CSF) samples. We found that the quality of results varied greatly among workflows, and interestingly, heterogeneous combinations of algorithms often performed better than the homogenous workflows. Our scoring method showed that the union of feature matrices of different workflows outperformed the original homogenous workflows in some cases. msCompare is open source software (https://trac.nbic.nl/mscompare), and we provide a web-based data processing service for our framework by integration into the Galaxy server of the Netherlands Bioinformatics Center (http://galaxy.nbic.nl/galaxy) to allow scientists to determine which combination of modules provides the most accurate processing for their particular LC-MS data sets. PMID- 22318372 TI - Osteoinduction: a review of old concepts with new standards. AB - Since the discovery of osteoinduction in the early 20th century, innovative biomaterials with osteoinductive potential have emerged. Over the last 50 years, however, our ability to describe biological phenomena accurately has been improved dramatically by advancements in cell and molecular biology. The aim of this review is to divide the osteoinduction phenomenon into 3 principles: (1) mesenchymal cell recruitment, (2) mesenchymal differentiation to bone-forming osteoblasts, and (3) ectopic bone formation in vivo. Furthermore, this review formulates guidelines for in vitro and in vivo experimental testing for accurately defining new biomaterials as osteoinductive. The use of growth factors with osteoinductive potential in periodontal and oral surgery is discussed. These concepts and guidelines aim to guide the future direction of emerging biomaterials in bone regeneration. PMID- 22318371 TI - Survivin SNP-carcinogen interactions in oral cancer. AB - In Taiwan, oral cancer is causally associated with environmental carcinogens. Survivin is an anti-apoptotic protein and is generally considered a marker of malignancy. The current study explored the combined effect of survivin gene polymorphisms and environmental carcinogens on the risk and clinico-pathological development of oral cancer. Five single-nucleotide polymorphisms (SNPs) of survivin genes from 439 male patients with oral cancer and 424 male control participants (who did not have cancer) were analyzed. The survivin -31GG, +9194 GG, and +9809 TT homozygotes exhibited higher risk for oral cancer compared with the corresponding ancestral genotype, after adjustment for related confounders. The survivin -31, +9194, and +9809 SNPs combined with betel quid chewing and/or tobacco consumption could robustly elevate susceptibility to oral cancer. The distribution frequency of the -31 G: +9194 A: +9809 T haplotype was significantly higher in oral cancer patients than in control participants. These results suggest that survivin gene polymorphisms and their interactions with environmental carcinogens may increase susceptibility to oral cancer in Taiwanese men. ABBREVIATIONS: AOR, adjusted odds ratio; CI, confidence intervals; PCR, polymerase chain-reaction; SNP, single-nucleotide polymorphisms. PMID- 22318373 TI - Randomized controlled trial on physical therapy for TMJ closed lock. AB - This study evaluated the one-year effect of physical therapy on pain and mandibular dysfunction associated with anterior disc displacement without reduction of the temporomandibular joint (closed lock). Forty-nine individuals were randomly assigned to either a physical therapy group [n = 23, mean age (SD) 34.7 (14.0) yrs] or a control group [n = 26, mean age 38.5 (15.1) yrs]. At baseline and after 3, 6, 12, 26, and 52 wks, pain and mandibular function were evaluated. All patients received extensive information about avoiding parafunctions and oral habits on all evaluation days. The physical therapy group received, in a 6-week period, 9 sessions of physical therapy, including joint mobilization, exercises, and massage, and the information on avoiding parafunctions and oral habits was repeated each time. All pain variables decreased, and all function variables increased significantly over time for both groups. The interaction between time and treatment group was not significant. Hence, physical therapy had no significant additional effect in patients with anterior disc displacement, without reduction, of the temporomandibular joint (ClinicalTrials.gov number, CT01475630). PMID- 22318374 TI - Description of a large urban school-located 2009 pandemic H1N1 vaccination campaign, New York City 2009-2010. AB - In the spring of 2009, New York City (NYC) experienced the emergence and rapid spread of pandemic influenza A H1N1 virus (pH1N1), which had a high attack rate in children and caused many school closures. During the 2009 fall wave of pH1N1, a school-located vaccination campaign for elementary schoolchildren was conducted in order to reduce infection and transmission in the school setting, thereby reducing the impact of pH1N1 that was observed earlier in the year. In this paper, we describe the planning and outcomes of the NYC school-located vaccination campaign. We compared consent and vaccination data for three vaccination models (school nurse alone, school nurse plus contract nurse, team). Overall, >1,200 of almost 1,600 eligible schools participated, achieving 26.8% consent and 21.5% first-dose vaccination rates, which did not vary significantly by vaccination model. A total of 189,902 doses were administered during two vaccination rounds to 115,668 students at 998 schools included in the analysis; vaccination rates varied by borough, school type, and poverty level. The team model achieved vaccination of more children per day and required fewer vaccination days per school. NYC's campaign is the largest described school located influenza vaccination campaign to date. Despite substantial challenges, school-located vaccination is feasible in large, urban settings, and during a public health emergency. PMID- 22318375 TI - Predictors of suicide and suicide attempt in subway stations: a population-based ecological study. AB - Suicidal behavior on the subway often involves young people and has a considerable impact on public life, but little is known about factors associated with suicides and suicide attempts in specific subway stations. Between 1979 and 2009, 185 suicides and 107 suicide attempts occurred on the subway in Vienna, Austria. Station-specific suicide and suicide attempt rates (defined as the frequency of suicidal incidents per time period) were modeled as the outcome variables in bivariate and multivariate Poisson regression models. Structural station characteristics (presence of a surveillance unit, train types used, and construction on street level versus other construction), contextual station characteristics (neighborhood to historical sites, size of the catchment area, and in operation during time period of extensive media reporting on subway suicides), and passenger-based characteristics (number of passengers getting on the trains per day, use as meeting point by drug users, and socioeconomic status of the population in the catchment area) were used as the explanatory variables. In the multivariate analyses, subway suicides increased when stations were served by the faster train type. Subway suicide attempts increased with the daily number of passengers getting on the trains and with the stations' use as meeting points by drug users. The findings indicate that there are some differences between subway suicides and suicide attempts. Completed suicides seem to vary most with train type used. Suicide attempts seem to depend mostly on passenger-based characteristics, specifically on the station's crowdedness and on its use as meeting point by drug users. Suicide-preventive interventions should concentrate on crowded stations and on stations frequented by risk groups. PMID- 22318376 TI - Brief review: The LMA SupremeTM supraglottic airway. AB - PURPOSE: This article is a review of the efficacy and safety of the Laryngeal Mask Airway (LMA) SupremeTM as a stand-alone supraglottic airway during general anesthesia and as a conduit for tracheal intubation. Relevant articles were obtained using MEDLINE (1948-July 2011) and EMBASE (1980-July 2011). Only original studies with adult human patients and published in English were selected. PRINCIPAL FINDINGS: The LMA Supreme was found to be comparable with the LMA ProsealTM with regard to success rate, insertion time, and complications. However, in three studies, oropharyngeal leak pressure was higher with the LMA Proseal than with the LMA Supreme. The LMA Supreme was superior to the LMA ClassicTM with regard to insertion time and oropharyngeal seal pressure. The LMA Supreme was also used successfully in two difficult airway cases, and it has been used as a conduit for tracheal intubation by utilizing an intubation introducer (gum elastic bougie) and subsequently railroading an endotracheal tube over the bougie into the trachea. Techniques for achieving tracheal intubation include the use of the Aintree Intubation Catheter(r), a guidewire-exchange catheter, a gum elastic bougie, and a small (<6.0 mm internal diameter) endotracheal tube. CONCLUSION: The LMA Supreme has been shown to be a safe and efficacious device as a stand-alone supraglottic airway and may also be used as a conduit for tracheal intubation. Further trials are needed to determine the efficacy of the LMA Supreme compared with other supraglottic airways in both elective and emergent airway management situations. PMID- 22318378 TI - [Peer review and impact factor as well as preferential reading give hint to authors of papers for clinical issues]. PMID- 22318379 TI - [Rating and ranking of medical journals: a randomised controlled evaluation of impact factor and number of listed journals]. AB - BACKGROUND: The impact factor is a purely bibliometric parameter built on a number of publications and their citations that occur within clearly defined periods. Appropriate interpretation of the impact factor is important as it is also used worldwide for the evaluation of research performance. RESEARCH QUESTION: It is assumed that the number of medical journals reflects the extent of diseases and patient populations involved and that the number is correlated with the level of the impact factor. METHOD: 174 category lists (Subject Categories) are included in the area Health Sciences of the ISI Web of Knowledge of Thomson Reuters, 71 of which belong to the field of medicine and 50 of which have a clinical and/or application-oriented focus. These alphabetically arranged 50 category lists were consecutively numbered, randomized by odd and even numbers, respectively, into 2 equal-sized groups and then grouped according to organ specialities, sub-specialities and cross-disciplinary fields. By tossing up a coin it was decided which group should be evaluated first. Only then the category lists were downloaded and the number of journals, as well as the impact factors of journals ranking number 1 and 2, as well as the impact factors of journals at the end of the first third and at the end of the first half of each category list were compared. RESULTS: The number of journals per category list varies considerably between 5 and 252. The lists of organ specialties and cross disciplinary fields include more than three times as many journals as those of the sub-specialities; the highest numbers of journals are listed for the cross disciplinary fields. The level of impact factor of journals that rank number 1 in the lists varies considerably and ranges from 3,058 to 94,333; a similar variability exists for the journals at rank 2. On the other hand, the impact factor of journals at the end of the first third of the lists varies from 1,214 and 3,953, and for those journals at the end of the first half of a respective category list it varies from 0,609 and 2,872. The slope of the straight correlation line between the level of impact factors of journals at rank 1 and 2 with the number of listed journals varies from 0,0756 and 0,2651 (correlation coefficients between 0,49 and 0,96). For the journals ranking further down in the lists the straight correlation lines run almost horizontally or with inverse slope. CONCLUSIONS: This current analysis adds to the knowledge for an appropriate interpretation of the impact factor. Generally, greater importance should be given to the ranking of a journal within a corresponding category list. PMID- 22318380 TI - Sequential self-assembly in metal-organic frameworks. AB - This perspective discusses the use of sequential self-assembly in the construction of metal-organic frameworks through the systematic insertion, replacement, and removal of organic structural building units. We review previous works that can be classified as such sequential self-assembly in multidimensional MOFs. PMID- 22318381 TI - Disruption of TNF-alpha/TNFR1 function in resident skin cells impairs host immune response against cutaneous vaccinia virus infection. AB - One strategy adopted by vaccinia virus (VV) to evade the host immune system is to encode homologs of TNF receptors (TNFRs) that block TNF-alpha function. The response to VV skin infection under conditions of TNF-alpha deficiency, however, has not been reported. We found that TNFR1-/- mice developed larger primary lesions, numerous satellite lesions, and higher skin virus levels after VV scarification. Following their recovery, VV-scarified TNFR1-/- mice were fully protected against challenge with a lethal intranasal dose of VV, suggesting these mice had developed an effective memory immune response. A functional systemic immune response was further demonstrated by enhanced production of VV-specific IFN-gamma and VV-specific CD8(+) T cells in spleens and draining lymph nodes. Interestingly, bone marrow (BM)-reconstitution studies using wild-type (WT) BM in TNFR1-/- host mice, but not TNFR1-/- BM in WT host mice, reproduced the original results seen in TNFR1-/- mice, indicating that TNFR1 deficiency in resident skin cells, rather than hematopoietic cells, accounts for the impaired cutaneous immune response. Our data suggest that lack of TNFR1 leads to a skin-specific immune deficiency, and that resident skin cells have a crucial role in mediating an optimal immune defense to VV cutaneous infection via TNF-alpha/TNFR1 signaling. PMID- 22318382 TI - The double-stranded RNA analogue polyinosinic-polycytidylic acid induces keratinocyte pyroptosis and release of IL-36gamma. AB - IL-36 is the common name for the three IL-1 family members IL-36alpha, IL-36beta, and IL-36gamma, formerly known as IL-1F6, IL-1F8, and IL-1F9, respectively. IL-36 appears to have pro-inflammatory activities; however, the physiological function of these cytokines remains unknown. Expression of IL-36 by keratinocytes implies its possible involvement in innate immune responses in the skin. We observed that, of the three IL-36 isoforms, human keratinocytes express high levels of IL 36gamma. IL-36gamma mRNA expression was dramatically induced by the Toll-like receptor ligands polyinosinic-polycytidylic acid (poly(I:C)) and flagellin. Surprisingly, the IL-36gamma protein was released by cells treated with poly(I:C), but remained intracellular in cells treated with flagellin only. poly(I:C), but not flagellin, induced cell death and caspase-3/7 activation. Inhibition of caspase-3/7 and caspase-1 blocked extracellular release of IL 36gamma from poly(I:C)-treated cells. Furthermore, caspase-1 inhibition prevented poly(I:C)-induced caspase-3/7 activation. Interestingly, transcription of the gene IL36G was dependent on caspase-1, but not caspase-3/7, activation. This demonstrates that the pathways leading to IL36G transcription and caspase-3/7 activation branch after caspase-1. This divergence of the pathways allows the cells to enter a state of de novo protein synthesis before committing to pyroptosis. Overall, our observations suggest that IL-36gamma may be an alarmin that signals the cause, e.g., viral infection, of cell death. PMID- 22318383 TI - Tretinoin and the prevention of keratinocyte carcinoma (Basal and squamous cell carcinoma of the skin): a veterans affairs randomized chemoprevention trial. AB - Keratinocyte carcinoma (KC) is the most common cancer in the United States, with no proven means for prevention other than systemic retinoids, which have significant toxicity, and sunscreen. Topical tretinoin has been used for KC chemoprevention, although this use is unproven. Hence, we conducted the randomized Veterans Affairs Topical Tretinoin Chemoprevention Trial of high-dose topical tretinoin for KC prevention. We randomized 1,131 patients to topical 0.1% tretinoin or a matching vehicle control for 1.5-5.5 years. The primary outcomes were time to development of new basal cell carcinoma (BCC) and new invasive squamous cell carcinoma (SCC) on the face or ears. The effects were not significant (P=0.3 for BCC and P=0.4 for SCC). The proportions of the tretinoin and control groups who developed a BCC at 5 years were 53 and 54% and an invasive SCC at 5 years were 28 and 31%. These differences (95% confidence intervals) were: for BCC, 1.0% (-6.5, 8.6%); for SCC, 3.6% (-3.1, 10.3%). No differences were observed in any cancer-related end points or in actinic keratosis counts. The only quality of life difference was worse symptoms in the tretinoin group at 12 months after randomization. This trial in high-risk patients demonstrates that high-dose topical tretinoin is ineffective at reducing risk of KCs. PMID- 22318384 TI - Mutations in the SASPase gene (ASPRV1) are not associated with atopic eczema or clinically dry skin. PMID- 22318385 TI - Lack of evidence for association of VEGF polymorphisms in Swedish patients with psoriasis. PMID- 22318386 TI - Modulation of activated leukocyte cell adhesion molecule-mediated invasion triggers an innate immune gene response in melanoma. AB - Activated leukocyte cell adhesion molecule (ALCAM/CD166) is a progression marker of a variety of cancers, including melanoma, and is a marker for mesenchymal stem cells. ALCAM expression triggers matrix metalloproteinase activity and correlates with the transition between superficial melanoma growth and deep dermal invasion in vivo. We previously showed that manipulating ALCAM functionality could both decrease and increase melanoma invasion, depending on the manner by which ALCAM function was altered. How ALCAM exerts these opposing invasive phenotypes remained elusive. In the present study, we analyzed differences in melanoma cell gene expression in two- and three-dimensional cultures as function of ALCAM mediated adhesion. We identified a cluster of genes highly responsive to ALCAM functionality and relevant for melanoma invasion. This cluster is characterized by known invasion-related genes similar to L1 neuronal cell adhesion molecule and showed a remarkable induction of several innate immune genes. Unexpectedly, we identified major variations in the expression of genes related to an immunological response when modulating ALCAM function, including complement factors C1r and C1s. The expression and function of these proteinases were confirmed in protein assays and in vivo. Together, our results demonstrate a link between ALCAM functionality and the immune transcriptome, and support the assumption that ALCAM-ALCAM interactions could function as a cell signaling complex to promote melanoma tumor invasion. PMID- 22318387 TI - ORAI1 Ca(2+) channels control endothelin-1-induced mitogenesis and melanogenesis in primary human melanocytes. AB - UV radiation of the skin triggers keratinocytes to secrete endothelin-1 (ET-1) that binds to endothelin receptors on neighboring melanocytes. Melanocytes respond with a prolonged increase in intracellular Ca(2+) concentration ([Ca(2+)](i)), which is necessary for proliferation and melanogenesis. A major fraction of the Ca(2+) signal is caused by entry through Ca(2+)-permeable channels of unknown identity in the plasma membrane. ORAI Ca(2+) channels are molecular determinants of Ca(2+) release-activated Ca(2+) (CRAC) channels and are expressed in many tissues. Here, we show that ORAI1-3 and their activating partners stromal interaction molecules 1 and 2 (STIM1 and STIM2) are expressed in human melanocytes. Although ORAI1 is the predominant ORAI isoform, STIM2 mRNA expression exceeds STIM1. Inhibition of ORAI1 by 2-aminoethoxydiphenyl borate (2 APB) or downregulation of ORAI1 by small interfering RNA (siRNA) reduced Ca(2+) entry and CRAC current amplitudes in activated melanocytes. In addition, suppression of ORAI1 caused reduction in the ET-1-induced cellular viability, melanin synthesis, and tyrosinase activity. Our results imply a role for ORAI1 channels in skin pigmentation and their potential involvement in UV-induced stress responses of the human skin. PMID- 22318388 TI - Irradiation of skin with visible light induces reactive oxygen species and matrix degrading enzymes. AB - Daily skin exposure to solar radiation causes cells to produce reactive oxygen species (ROS), which are a primary factor in skin damage. Although the contribution of the UV component to skin damage has been established, few studies have examined the effects of non-UV solar radiation on skin physiology. Solar radiation comprises <10% of UV, and thus the purpose of this study was to examine the physiological response of skin to visible light (400-700 nm). Irradiation of human skin equivalents with visible light induced production of ROS, proinflammatory cytokines, and matrix metalloproteinase (MMP)-1 expression. Commercially available sunscreens were found to have minimal effects on reducing visible light-induced ROS, suggesting that UVA/UVB sunscreens do not protect the skin from visible light-induced responses. Using clinical models to assess the generation of free radicals from oxidative stress, higher levels of free radical activity were found after visible light exposure. Pretreatment with a photostable UVA/UVB sunscreen containing an antioxidant combination significantly reduced the production of ROS, cytokines, and MMP expression in vitro, and decreased oxidative stress in human subjects after visible light irradiation. Taken together, these findings suggest that other portions of the solar spectrum aside from UV, particularly visible light, may also contribute to signs of premature photoaging in skin. PMID- 22318389 TI - Intrinsic gene expression subsets of diffuse cutaneous systemic sclerosis are stable in serial skin biopsies. AB - Skin biopsy gene expression was analyzed by DNA microarray from 13 diffuse cutaneous systemic sclerosis (dSSc) patients enrolled in an open-label study of rituximab, 9 dSSc patients not treated with rituximab, and 9 healthy controls. These data recapitulate the patient "intrinsic" gene expression subsets described previously, including fibroproliferative, inflammatory, and normal-like groups. Serial skin biopsies showed consistent and non-progressing gene expression over time, and importantly, the patients in the inflammatory subset do not move to the fibroproliferative subset, and vice versa. We were unable to detect significant differences in gene expression before and after rituximab treatment, consistent with an apparent lack of clinical response. Serial biopsies from each patient stayed within the same gene expression subset, regardless of treatment regimen or the time point at which they were taken. Collectively, these data emphasize the heterogeneous nature of SSc and demonstrate that the intrinsic subsets are an inherent, reproducible, and stable feature of the disease that is independent of disease duration. Moreover, these data have fundamental importance for the future development of personalized therapy for SSc; drugs targeting inflammation are likely to benefit those patients with an inflammatory signature, whereas drugs targeting fibrosis are likely to benefit those with a fibroproliferative signature. PMID- 22318390 TI - Natural gene therapy may occur in all patients with generalized non-Herlitz junctional epidermolysis bullosa with COL17A1 mutations. AB - Mutations in the type XVII collagen gene (COL17A1) result in the blistering disorder non-Herlitz junctional epidermolysis bullosa (JEB-nH). The incidence of revertant mosaicism, also called "natural gene therapy", was identified in a cohort of 14 patients with JEB-nH caused by COL17A1 mutations in the Netherlands. Five different in vivo reversions, all correcting the germ-line COL17A1 mutation c.2237delG in exon 30, were found in four mosaic JEB-nH patients. The correcting DNA changes involved a wide variety of somatic mutations, from which an indel mutation (c.2228-101_2263+70delins15) and a large deletion of 2,165 base pairs (c.2227+153_2336-318del) have not been previously observed in patients with revertant mosaicism. Our results show that there is no preference for a repair mechanism. Moreover, revertant mosaicism was confirmed on a DNA level in 6 out of 10 generalized JEB-nH patients. Further, photo-material and clinical history of the other four generalized JEB-nH patients demonstrated that each patient has revertant skin patches. In contrast, revertant mosaicism was not detected in the four localized JEB-nH patients. The fact that so many, if not all, generalized JEB-nH COL17A1 patients have revertant patches offers opportunities for cell therapies in which the patient's own naturally corrected cells are used as a source. PMID- 22318391 TI - Differential IgG recognition of desmoglein 3 by paraneoplastic pemphigus and pemphigus vulgaris sera. PMID- 22318392 TI - Validation of GWAS loci for atopic dermatitis in a Singapore Chinese population. PMID- 22318393 TI - Primary B-CLL resistance to NK cell cytotoxicity can be overcome in vitro and in vivo by priming NK cells and monoclonal antibody therapy. AB - Despite recent advances with monoclonal antibody therapy, chronic lymphocytic leukemia (CLL) remains incurable. Natural killer (NK) cells are potent antitumoral effectors, particularly against hematological malignancies. Defective recognition of B-CLL leukemic cells by NK cells has been previously described. Here, we deciphered the mechanisms that hamper NK cell-mediated clearance of B CLL and evaluated the potential of NK cells as therapeutic tools for treatment of CLL. First of all, leukemic B cells resemble to normal B cells with a weak expression of ligands for NK receptors. Conversely, NK cells from B-CLL patients were functionally and phenotypically competent, despite a decrease of expression of the activating receptor NKp30. Consequently, resting allogeneic NK cells were unable to kill leukemic B cells in vitro. These data suggest that patients' NK cells cannot initiate a proper immune reaction due to a lack of leukemic cell recognition. We next set up a xenotransplantation mouse model to study NK-CLL cell interactions. Together with our in vitro studies, in vivo data revealed that activation of NK cells is required in order to control B-CLL and that activated NK cells synergize to enhance rituximab effect on tumor load. This study points out the requirements for immune system manipulation for treatment of B-CLL in combination with monoclonal antibody therapy. PMID- 22318394 TI - Safety and immunogenicity of multimeric-001--a novel universal influenza vaccine. AB - OBJECTIVE: A new vaccine, Multimeric-001, containing conserved linear epitopes from the HA, NP, and M1 proteins of influenza type A and type B strains was designed to protect against seasonal and pandemic influenza virus strains, regardless of mutations. We assessed its safety and tolerability and characterized humoral and cellular immune responses elicited by its administration. METHODS: Sixty healthy volunteers received either 250 or 500 MUg injections, with or without adjuvant (Montanide ISA 51VG), or matching placebo. Two intramuscular injections were administered, 21 days apart. RESULTS: Treatment was well tolerated and no significant adverse events were noted. Forty-two days after first injection, there was a 50-fold and 37-fold increase in IgG titers against Multimeric-001 protein, following the adjuvanted 500 and 250 MUg doses, respectively. Sera from immunized subjects lysed MDCK cells infected with strains of influenza representing the major strains that infect humans: H1N1, H3N2, and influenza B. Proliferation of peripheral blood mononuclear cells as well as increase in IL-2 and IFN-gamma secretion occurred following incubation with the vaccine. CONCLUSION: This vaccine model differs fundamentally from the current influenza virus vaccines, as it does not contain the variable regions of the virus hemagglutinin and hence does not induce hemagglutination inhibition antibodies that serve as surrogate markers for protection. In order to demonstrate the potential efficacy of the Multimeric-001, an alternative assay was employed, in which the lysis of MDCK cells infected with different virus strains was shown, with the involvement of the complement mechanism. The humoral and cellular responses suggest a cross-immunity of the vaccine toward influenza virus strains regardless of mutations. These results corroborate the protective effect of the vaccine, previously shown in animals. Larger-scale studies are under way to further substantiate the safety and efficacy of the vaccine candidate. PMID- 22318395 TI - A methodology for detecting field potentials from the external ear canal: NEER and EVestG. AB - An algorithm called the neural event extraction routine (NEER) and a method called Electrovestibulography (EVestG) for extracting field potentials (FPs) from artefact rich and noisy ear canal recordings is presented. Averaged FP waveforms can be used to aid detection of acoustic and or vestibular pathologies. FPs were recorded in the external ear canal proximal to the ear drum. These FPs were extracted using an algorithm called NEER. NEER utilises a modified complex Morlet wavelet analysis of phase change across multiple scales and a template matching (matched filter) methodology to detect FPs buried in noise and biological and environmental artefacts. Initial simulation with simulated FPs shows NEER detects FPs down to -30 dB SNR (power) but only 13-23% of those at SNR's <-6 dB. This was deemed applicable to longer duration recordings wherein averaging could be applied as many FPs are present. NEER was applied to detect both spontaneous and whole body tilt evoked FPs. By subtracting the averaged tilt FP response from the averaged spontaneous FP response it is believed this difference is more representative of the vestibular response. Significant difference (p < 0.05) between up and down whole body (supine and sitting) movements was achieved. Pathologic and physiologic evidence in support of a vestibular and acoustic origin is also presented. PMID- 22318396 TI - In vitro characterization of bicuspid aortic valve hemodynamics using particle image velocimetry. AB - The congenital bicuspid aortic valve (BAV) is associated with increased leaflet calcification, ascending aortic dilatation, aortic stenosis (AS) and regurgitation (AR). Although underlying genetic factors have been primarily implicated for these complications, the altered mechanical environment of BAVs could potentially accelerate these pathologies. The objective of the current study is to characterize BAV hemodynamics in an in vitro system. Two BAV models of varying stenosis and jet eccentricity and a trileaflet AV (TAV) were constructed from excised porcine AVs. Particle Image Velocimetry (PIV) experiments were conducted at physiological flow and pressure conditions to characterize fluid velocity fields in the aorta and sinus regions, and ensemble averaged Reynolds shear stress and 2D turbulent kinetic energy were calculated for all models. The dynamics of the BAV and TAV models matched the characteristics of these valves which are observed clinically. The eccentric and stenotic BAV showed the strongest systolic jet (V = 4.2 m/s), which impinged on the aortic wall on the non-fused leaflet side, causing a strong vortex in the non fused leaflet sinus. The magnitudes of TKE and Reynolds stresses in both BAV models were almost twice as large as comparable values for TAV, and these maximum values were primarily concentrated around the central jet through the valve orifice. The in vitro model described here enables detailed characterization of BAV flow characteristics, which is currently challenging in clinical practice. This model can prove to be useful in studying the effects of altered BAV geometry on fluid dynamics in the valve and ascending aorta. These altered flows can be potentially linked to increased calcific responses from the valve endothelium in stenotic and eccentric BAVs, independent of concomitant genetic factors. PMID- 22318397 TI - OMNI Scale of Perceived Exertion: mixed gender and race validation for Singapore children during cycle exercise. AB - The children's OMNI Scale of Perceived Exertion (RPE) has not been validated for children of Asian origin. The purpose was to validate the RPE for Singapore children, 12-15 years. 81 children of male and female of Chinese, Malay, and Indian ethnicities participated in the study. A cross-sectional, perceptual estimation paradigm using a multistage cycle ergometer protocol was used. Oxygen consumption ([Formula: see text]; ml min(-1)), heart rate (HR; beats min(-1)), and RPE for the Overall body (RPE-O), Legs (RPE-L), and Chest (RPE-C) were determined at the end of each continuously administered 3-min power output stage (PO) starting at 25 W with 25 W increments until exhaustion. For validation, linear regression analysis for all PO revealed that RPE-O, RPE-L, and RPE-C for each of the six gender-race and combined cohort distributed as positive linear functions of both [Formula: see text] (ml min(-1), ml kg(-1) min(-1)) and HR (beats min(-1)). All regression functions were statistically significant (P < 0.01). Differences between undifferentiated (RPE-O) and differentiated (RPE-L and RPE-C) at each PO stage were examined separately for the male (up to PO 8 [200 W]) and female (up to PO 5 [125 W]) cohorts. For the males, RPE-L was greater (P < 0.05) than both RPE-C and RPE-O only at PO 8. For the females, RPE-O was greater (P < 0.05) than RPE-C only at PO 3 and 4. OMNI Scale validity was established for male and female Asian children of Chinese, Malay, and Indian origin. Male and female children did not perceive the intensity of exertional perceptions to differ between the legs and the chest. As there were no differences between the undifferentiated and differentiated perceptual responses, a dominant signal was not observed. PMID- 22318398 TI - Inheritance and genetic mapping of two nuclear genes involved in nuclear cytoplasmic incompatibility in peas (Pisum sativum L.). AB - Genetic analysis was performed to finely map and assess the mode of inheritance of two unlinked nuclear genes Scs1 and Scs2 involved in incompatibility of the nuclear genome of the cultivated pea Pisum sativum subsp. sativum with the cytoplasm of the wild pea of the subspecies P. sativum subsp. elatius, accession VIR320. Based on the segregation of genotypes in the progeny of the test-crosses, we concluded that if the cytoplasm was inherited from the wild pea VIR320, the Scs1 allele from the cultivated pea was gametophyte lethal and sporophyte recessive lethal. The Scs2 allele from the cultivated pea reduced male gametophyte viability. In homozygote, Scs2 from cultivated parent brought about nuclear-cytoplasmic conflict manifested as chlorophyll deficiency, reduction of blade organs, and low pollen fertility of about 20%. In heterozygote, Scs1 and Scs2 genes reduced pollen fertility by ca 50 and 30%, respectively. The Scs1 and Scs2 genes involved in nuclear-cytoplasmic incompatibility were genetically mapped. The distance between the markers bordering Scs1 comprised about 2.5 cM on linkage group III. The map distance between the bordering markers in the neighborhood of Scs2 varied substantially from cross to cross in the range of 2.0 15.1 cM on linkage group V. PMID- 22318399 TI - Properties of metastable linkage NO isomers in Na2[Fe(CN)5NO].2H2O incorporated in mesopores of silica xerogels. AB - We study the properties of photoinduced metal-nitrosyl linkage isomers in sodium nitroprusside (SNP) as a function of particle size. By embedding the molecular complex at various concentrations into mesopores of silica xerogels the size of the particles can be adjusted. The ground state is characterized by X-ray diffraction, absorption and infrared spectroscopy. The physical properties of the photoswitched molecules were analysed by steady-state low-temperature absorption, infrared spectroscopy and by nanosecond transient absorption spectroscopy. The electronic structure as well as the activation energies of the metastable linkage isomers are independent of the particle size down to single isolated molecules, indicating that the SNP complexes are quasi-free inside the pores of the gel. PMID- 22318400 TI - Factors associated with failure to correct the international normalised ratio following fresh frozen plasma administration among patients treated for warfarin related major bleeding. An analysis of electronic health records. AB - This study assessed the frequency and factors associated with failure to correct international normalised ratio (INR) in patients administered fresh frozen plasma (FFP) for warfarin-related major bleeding. This retrospective database analysis used electronic health records from an integrated health system. Patients who received FFP between 01/01/2004 and 01/31/2010, and who met the following criteria were selected: major haemorrhage diagnosis the day before to the day after initial FFP administration; INR >=2 on the day before or the day of FFP and another INR result available; warfarin prescription within 90 days. INR correction (defined as INR <=1.3) was evaluated at the last available test up to one day following FFP. A total of 414 patients met selection criteria (mean age 75 years, 53% male, mean Charlson score 2.5). Patients presented with gastrointestinal bleeding (58%), intracranial haemorrhage (38%) and other bleed types (4%). The INR of 67% of patients remained uncorrected at the last available test up to one day following receipt of FFP. In logistic regression analysis, the INR of patients who were older, those with a Charlson score of 4 or greater, and those with non-ICH bleeds (odds ratio vs. intracranial bleeding 0.48; 95% confidence interval 0.31-0.76) were more likely to remain uncorrected within one day following FFP administration. In an alternative definition of correction, (INR <=1.5), 39% of patients' INRs remained uncorrected. For a substantial proportion of patients, the INRs remain inadequately or uncorrected following FFP administration, with estimates varying depending on the INR threshold used. PMID- 22318401 TI - Evaluation of CTLA-4 expression and relevance as a novel prognostic factor in patients with non-small cell lung cancer. AB - The role of CTLA-4 in negative regulation of T-cell mediated immune response is particularly well established. Much less is known about its expression and function in tumour cells, and to our knowledge, no data are available on its possible impact on prognosis of NSCLC patients. We investigated CTLA-4 expression and prognostic role in 81 patients with radically resected stage I-III NSCLC. The analysis was performed by tissue microarray immunohistochemistry, and the median H-score of 20 was used as a threshold to define CTLA-4 overexpressing tumours. Correlation with standard prognostic factors was performed by using absolute and relative fold change indexes. Hazard ratios (HR) and corresponding 95% confidence limits (95% CL) were computed through the Cox model. A higher frequency of CTLA-4 overexpression (>20) was found in non-squamous than in squamous NSCLC (52.8 vs. 35.7%) and in Ki67 <= 15 expressing tumours, as compared to those with Ki67 > 15 (51.5 vs. 38.7%). A reduced death rate was found in CTLA-4 overexpressing tumours (HR = 0.60, 95% CL = 0.28/1.23), and a further decrease was observed when considering tumours with CTLA-4 > 20 and Ki67 <= 15, in comparison with tumours with CTLA-4 <= 20 and Ki67 > 15 (HR = 0.41; 95% CL = 0.15/1.13). Our observational and exploratory study provides a first and promising indication for an independent prognostic effect of CTLA-4 overexpression in radically resected NSCLC. We presume that this effect relies on modulation of the interaction of microscopic disease with CTLA-4-ligands expressing cells leading to NSCLC cell death. PMID- 22318402 TI - The influence of anesthesia on cardiac repolarization. AB - The drugs and techniques used in contemporary anaesthesia may provoke numerous side effects, including cardiac rhythm disturbances. The prolongation of the repolarization time, reflected by the QT interval in a surface electrocardiogram, is one of the mechanisms that lead to the occurrence of arrhythmias. In the paper, we present the primary mechanism that is responsible for QT interval prolongation and subsequent torsade de pointes ventricular tachycardia. The influence of anesthetics, regional anesthesia and perioperative supportive therapy on cardiac repolarization is described. PMID- 22318403 TI - Is simulation efficient to improve anesthetists' performance and patient outcome? PMID- 22318404 TI - Expedient synthesis of pseudo-Pro-containing peptides: towards constrained peptidomimetics and foldamers. AB - The reaction of sulfonyl peptides containing L- or D-configured Ser or Thr with bis(succinimidyl) carbonate in the presence of a catalytic amount of a base affords, in solution or in the solid phase, the corresponding peptides with one or two, consecutive or alternate oxazolidin-2-ones (Oxd). The Oxd ring can be regarded to as a pseudo-Pro with an exclusively trans conformation of the preceding peptide bond; homochiral Oxd-containing peptides adopt extended conformations, while the presence of a D-configured Oxd favours folded conformations. PMID- 22318405 TI - Microfluidic biomechanical assay for red blood cells parasitized by Plasmodium falciparum. AB - Red blood cells parasitized by Plasmodium falciparum can be distinguished from uninfected cells and characterized on the basis of reduced deformability. To enable improved and simplified analysis, we developed a microfluidic device to measure red blood cell deformability using precisely controlled pressure. Individual red blood cells are deformed through multiple funnel-shaped constrictions with openings ranging from 5 down to 1 MUm. Precisely controlled pressures are generated on-chip using a microfluidic circuit that attenuates an externally applied pressure by a factor of 100. The pressures required to squeeze each cell through the constriction are used as a readout to determine the intrinsic stiffness of each cell. Using this method, parasitized cells from ring through schizont stages were shown to be 1.5 to 200 times stiffer than uninfected cells. The measured deformability values of uninfected and parasitized cells showed clearly distinct distributions, demonstrating the potential of using this technique to study the pathophysiology of this disease, and the effect of potential drugs. PMID- 22318406 TI - Modeling of biocide action against biofilm. AB - We consider the mathematical model of dynamic antimicrobial action against bacterial biofilms. A mixture model is used in which the biofilm consisting of live and dead bacteria is modeled as one fluid component, while the solvent containing biocide is modeled as the other, and each component is represented by its volume fraction. The whole system is assumed to be an incompressible fluid and the velocity is governed by the Navier-Stokes equation. Biocide kills the live bacteria and its transport is governed by an advection-reaction-diffusion equation. Certain biocide also weakens the mechanical cohesiveness of the biofilm and results in biofilm removal under the shear stress of the external flow. Spatial and temporal patterns of antimicrobial action of three different biocides are considered and numerical simulation results by finite difference method are presented. PMID- 22318407 TI - Revealing barriers and facilitators to use a new genetic test: comparison of three user involvement methods. AB - We compared three common user involvement methods in revealing barriers and facilitators from intended users that might influence their use of a new genetic test. The study was part of the development of a new genetic test on the susceptibility to hand eczema for nurses. Eighty student nurses participated in five focus groups (n = 33), 15 interviews (n = 15) or questionnaires (n = 32). For each method, data were collected until saturation. We compared the mean number of items and relevant remarks that could influence the use of the genetic test obtained per method, divided by the number of participants in that method. Thematic content analysis was performed using MAXQDA software. The focus groups revealed 30 unique items compared to 29 in the interviews and 21 in the questionnaires. The interviews produced more items and relevant remarks per participant (1.9 and 8.4 pp) than focus groups (0.9 and 4.8 pp) or questionnaires (0.7 and 2.3 pp). All three involvement methods revealed relevant barriers and facilitators to use a new genetic test. Focus groups and interviews revealed substantially more items than questionnaires. Furthermore, this study suggests a preference for the use of interviews because the number of items per participant was higher than for focus groups and questionnaires. This conclusion may be valid for other genetic tests as well. PMID- 22318408 TI - Decision to evacuate a hospital during an emergency: the safe way or the leader's way? AB - Hospitals have frequently been evacuated because of natural or man-made disasters. In this article, we identify elements to be considered when confronted with the possibility of hospital evacuation. Hospital evacuation may have a significant impact on the surrounding community and the overall population. When the patients in a hospital are placed at risk, hospital leadership often decides to evacuate the facility to safeguard the well-being of both patients and staff. Such a decision is not likely to be criticized. We present various considerations. The effect of evacuation on patients, hospital staff, family members, the community, and even the nation as a whole, as well as repercussions affecting potential patients should be integral to the decision-making process and parallel to the risk assessment. PMID- 22318409 TI - Pulse-plethysmographic variables in hemodynamic assessment during mannitol infusion. AB - Plethysmographic signal using pulse oximetry may be used to assess fluid status of patients during surgery as it resembles arterial pressure waveform. This will avoid placement of invasive arterial lines. This study was designed to find out whether intravascular volume changes induced by mannitol bolus in neurosurgical patients are detected by variations in arterial pressure and plethysmographic waveforms and also to assess the strength of correlation between different variables derived from these two waveforms. The time difference between the onset of arterial and plethysmographic waveforms as means of significant hemodynamic changes was also evaluated. Forty one adult ASA I and II neurosurgical patients requiring mannitol infusion were recruited. Arterial line and plethysmographic probe were placed in the same limb. Digitized waveforms were collected before, at the end, and 15, 30 and 60 min after mannitol infusion. Using MATLAB, the following parameters were collected for three consecutive respiratory cycles, systolic pressure variation (SPV), pulse pressure variation (PPV), plethysmographic peak variation (Pl-PV), plethysmographic amplitude variation (Pl AV) and blood pressure-plethysmographic time lag (BP-Pleth time lag). Changes in above parameters over the study period were studied using repeated measure analysis of variance. Correlation between the parameters was analysed. SPV and Pl PV showed significant increase at 15, 30 and 60 min compared to end of mannitol infusion (P < 0.01 for SPV; P < 0.05 for Pl-PV). PPV and Pl-AV showed significant increase only at 30 min (P < 0.05). The correlation between ?SPV-?Pl-PV, ?PPV-?Pl AV and ?SPV-?BP-Pleth time lag were significant (r = 0.3; P < 0.01). SPV and time lag had no significant interaction. Pl-PV correlates well with SPV following mannitol infusion and can be used as an alternative to SPV. (BP-Pleth) time-lag promises to be an important parameter in assessing the state of peripheral vascular resistance and deserves further investigation. PMID- 22318410 TI - Quasiclassical trajectory calculations of hydrogen absorption in the (NaAlH4)2Ti system on a model analytical potential energy surface. AB - We performed a quasiclassical trajectory dynamics study on a model analytical 21 dimensional (7 active atoms) potential energy surface (PES) to examine in detail the mechanism of the hydrogen absorption in a simple (NaAlH(4))(2)Ti model system. The reaction involves a capture of H(2) by the Ti centre and formation of the (eta(2)-H(2))Ti(NaAlH(3))(2) coordination complex containing the side-on bonded dihydrogen ligand. The calculated rate constant corresponds to a very fast capture of H(2) by the Ti coordination sphere without a demonstrable barrier. This implies that this step is not the rate-determining step in the complex multi step process of the NaAlH(4) recovery. The model analytical PES captures the essence of this reaction well and the corresponding energy contours compare favourably to those based on the all-atom hybrid density functional theory calculations. PMID- 22318411 TI - A 12-year-old boy with severe mucositis: extrapulmonary manifestation of Mycoplasma pneumoniae infection. PMID- 22318412 TI - Mapping of alpha-neo-endorphin- and neurokinin B-immunoreactivity in the human brainstem. AB - We have studied the distribution of alpha-neo-endorphin- or neurokinin B immunoreactive fibres and cell bodies in the adult human brainstem with no prior history of neurological or psychiatric disease. A low density of alpha-neo endorphin-immunoreactive cell bodies was only observed in the medullary central gray matter and in the spinal trigeminal nucleus (gelatinosa part). Alpha-neo endorphin-immunoreactive fibres were moderately distributed throughout the human brainstem. A high density of alpha-neo-endorphin-immunoreactive fibres was found only in the solitary nucleus (caudal part), in the spinal trigeminal nucleus (caudal part), and in the gelatinosa part of the latter nucleus. Neurokinin B immunoreactive cell bodies (low density) were found in the periventricular central gray matter, the reticular formation of the pons and in the superior colliculus. The distribution of the neurokinin-immunoreactive fibres was restricted. In general, for both neuropeptides the density of the immunoreactive fibres was low. In the human brainstem, the proenkephalin system was more widely distributed than the prodynorphin system, and the preprotachykinin A system (neurokinin A) was more widely distributed than the preprotachykinin B system (neurokinin B). PMID- 22318413 TI - Forced to be free? Increasing patient autonomy by constraining it. AB - It is universally accepted in bioethics that doctors and other medical professionals have an obligation to procure the informed consent of their patients. Informed consent is required because patients have the moral right to autonomy in furthering the pursuit of their most important goals. In the present work, it is argued that evidence from psychology shows that human beings are subject to a number of biases and limitations as reasoners, which can be expected to lower the quality of their decisions and which therefore make it more difficult for them to pursue their most important goals by giving informed consent. It is further argued that patient autonomy is best promoted by constraining the informed consent procedure. By limiting the degree of freedom patients have to choose, the good that informed consent is supposed to protect can be promoted. PMID- 22318414 TI - Wish-fulfilling medicine in practice: a qualitative study of physician arguments. AB - There has been a move in medicine towards patient-centred care, leading to more demands from patients for particular therapies and treatments, and for wish fulfilling medicine: the use of medical services according to the patient's wishes to enhance their subjective functioning, appearance or health. In contrast to conventional medicine, this use of medical services is not needed from a medical point of view. Boundaries in wish-fulfilling medicine are partly set by a physician's decision to fulfil or decline a patient's wish in practice. In order to develop a better understanding of how wish-fulfilling medicine occurs in practice in The Netherlands, a qualitative study (15 semistructured interviews and 1 focus group) was undertaken. The aim was to investigate the range and kind of arguments used by general practitioners and plastic surgeons in wish fulfilling medicine. These groups represent the public funded realm of medicine as well as privately paid for services. Moreover, GPs and plastic surgeons can both be approached directly by patients in The Netherlands. The physicians studied raised many arguments that were expected: they used patient autonomy, risks and benefits, normality and justice to limit wish-fulfilling medicine. In addition, arguments new to this debate were uncovered, which were frequently used to justify compliance with a patient's request. Such arguments seem familiar from conventional medicine, including empathy, the patient-doctor relationship and reassurance. Moreover, certain arguments that play a significant role in the literature on wish-fulfilling medicine and enhancement were not mentioned, such as concepts of disease and the enhancement-treatment dichotomy and 'suspect norms'. PMID- 22318415 TI - Acute distal tibiofibular syndesmosis injury: a systematic review of suture button versus syndesmotic screw repair. AB - PURPOSE: Recently, a new suture-button fixation device has emerged for the treatment of acute distal tibiofibular syndesmotic injuries and its use is rapidly increasing. The current systematic review was undertaken to compare the biomechanical properties, functional outcome, need for implant removal, and the complication rate of syndesmotic disruptions treated with a suture-button device with the current 'gold standard', i.e. the syndesmotic screw. METHOD: A literature search in the electronic databases of the Cochrane Library, EMbase, Pubmed Medline, and Google Scholar, between January 1st 2000 to December 1st 2011, was conducted to identify studies in which unstable ankle fractures with concomitant distal tibiofibular syndesmotic injury were treated with either a syndesmotic screw or a suture-button device. RESULTS: A total of six biomechanical studies, seven clinical full-text studies and four abstracts on the TightRope system, and 27 studies on syndesmotic screw or bolt fixation were identified. The AOFAS of 133 patients treated with TightRope was 89.1 points, with an average study follow-up of 19 months. The AOFAS score in studies with 253 patients treated with syndesmotic screws (metallic and absorbable) or bolts was 86.3 points, with an average study follow-up of 42 months. Two studies reported an earlier return to work in the TightRope group. Implant removal was reported in 22 (10%) of 220 patients treated with a TightRope (range, 0-25%), in the screw or bolt group the average was 51.9% of 866 patients (range, 5.8-100%). CONCLUSION: The TightRope system has a similar outcome compared with the syndesmotic screw or bolt fixation, but might lead to a quicker return to work. The rate of implant removal is lower than in the syndesmotic screw group. There is currently insufficient evidence on the long-term effects of the TightRope and more uniform outcome reporting is desirable. In addition, there is a need for studies on cost effectiveness of the treatment of acute distal tibiofibular syndesmotic disruption treated with a suture-button device. PMID- 22318416 TI - Infections of the spine are still a great problem. PMID- 22318419 TI - Effects of atmospheric nitrogen deposition on remote freshwater ecosystems. AB - We review known and hypothesized effects of nitrogen (N) deposition owing to human activities on the chemistry, organisms, and ecosystem processes of remote oligotrophic freshwaters. Acidification is the best-known effect of N deposition on water chemistry, but additional effects include increased nutrient availability and alteration of the balance between N and other nutrients. Our synthesis of the literature, framed in a comprehensive model for the effects of N deposition on natural ecosystems, shows that all these effects can reduce biological diversity and alter ecosystem processes in remote freshwaters. N deposition is projected to grow worldwide in the near future and will interact with other global changes. Present effects on these fragile ecosystems may be only early signs of more radical impacts ahead. PMID- 22318420 TI - Erythropoietin, but not the correction of anemia alone, protects from chronic kidney allograft injury. AB - Anemia can contribute to chronic allograft injury by limiting oxygen delivery to tissues, particularly in the tubulointerstitium. To determine mechanisms by which erythropoietin (EPO) prevents chronic allograft injury we utilized a rat model of full MHC-mismatched kidney transplantation (Wistar Furth donor and Lewis recipients) with removal of the native kidneys. EPO treatment entirely corrected post-transplant anemia. Control rats developed progressive proteinuria and graft dysfunction, tubulointerstitial damage, inflammatory cell infiltration, and glomerulosclerosis, all prevented by EPO. Normalization of post-transplant hemoglobin levels by blood transfusions, however, had no impact on chronic allograft injury, indicating that EPO-mediated graft protection went beyond the correction of anemia. Compared to syngeneic grafts, control allografts had loss of peritubular capillaries, higher tubular apoptosis, tubular and glomerular oxidative injury, and reduced expression of podocyte nephrin; all prevented by EPO treatment. The effects of EPO were associated with preservation of intragraft expression of angiogenic factors, upregulation of the anti-apoptotic factor p-Akt in tubuli, and increased expression of Bcl-2. Inhibition of p-Akt by Wortmannin partially antagonized the effect of EPO on allograft injury and tubular apoptosis, and prevented EPO-induced Bcl-2 upregulation. Thus non-erythropoietic derivatives of EPO may be useful to prevent chronic renal allograft injury. PMID- 22318422 TI - Uremic solutes from colon microbes. AB - There is renewed interest in identifying organic waste solutes that are normally excreted by the kidneys and must be removed by renal replacement therapy when the kidneys fail. A large number of these waste solutes are produced by colon microbes. Mass spectrometry is expanding our knowledge of their chemical identity, and DNA sequencing technologies are providing new knowledge of the microbes and metabolic pathways by which they are made. There is evidence that the most extensively studied of the colon-derived solutes, indoxyl sulfate and p cresol sulfate, are toxic. Much more study is required to establish the toxicity of other solutes in this class. Because they are made in an isolated compartment by microbes, their production may prove simpler to suppress than the production of other waste solutes. To the extent that they are toxic, suppressing their production could improve the health of renal failure patients without the need for more intensive or prolonged dialysis. PMID- 22318421 TI - The kallikrein-kinin system in diabetic nephropathy. AB - Diabetic nephropathy is the major cause of end-stage renal disease worldwide. Although the renin-angiotensin system has been implicated in the pathogenesis of diabetic nephropathy, angiotensin I-converting enzyme inhibitors have a beneficial effect on diabetic nephropathy independently of their effects on blood pressure and plasma angiotensin II levels. This suggests that the kallikrein kinin system (KKS) is also involved in the disease. To study the role of the KKS in diabetic nephropathy, mice lacking either the bradykinin B1 receptor (B1R) or the bradykinin B2 receptor (B2R) have been commonly used. However, because absence of either receptor causes enhanced expression of the other, it is difficult to determine the precise functions of each receptor. This difficulty has recently been overcome by comparing mice lacking both receptors with mice lacking each receptor. Deletion of both B1R and B2R reduces nitric oxide (NO) production and aggravates renal diabetic phenotypes, relevant to either lack of B1R or B2R, demonstrating that both B1R and B2R exert protective effects on diabetic nephropathy presumably via NO. Here, we review previous epidemiological and experimental studies, and discuss novel insights regarding the therapeutic implications of the importance of the KKS in averting diabetic nephropathy. PMID- 22318423 TI - Lipopolysaccharide-pretreated plasmacytoid dendritic cells ameliorate experimental chronic kidney disease. AB - Plasmacytoid dendritic cells play important roles in inducing immune tolerance, preventing allograft rejection, and regulating immune responses in both autoimmune disease and graft-versus-host disease. In order to evaluate a possible protective effect of plasmacytoid dendritic cells against renal inflammation and injury, we purified these cells from mouse spleens and adoptively transferred lipopolysaccharide (LPS)-treated cells, modified ex vivo, into mice with adriamycin nephropathy. These LPS-treated cells localized to the kidney cortex and the lymph nodes draining the kidney, and protected the kidney from injury during adriamycin nephropathy. Glomerulosclerosis, tubular atrophy, interstitial expansion, proteinuria, and creatinine clearance were significantly reduced in mice with adriamycin nephropathy subsequently treated with LPS-activated plasmacytoid dendritic cells as compared to the kidney injury in mice given naive plasmacytoid dendritic cells. In addition, LPS-pretreated cells, but not naive plasmacytoid dendritic cells, convert CD4+CD25- T cells into Foxp3+ regulatory T cells and suppress the proinflammatory cytokine production of endogenous renal macrophages. This may explain their ability to protect against renal injury in adriamycin nephropathy. PMID- 22318424 TI - An update on the pathogenesis and treatment of IgA nephropathy. AB - Over the past two decades significant progress has been made in unravelling the complex pathogenesis of immunoglobulin A nephropathy (IgAN). Excess amounts of poorly galactosylated immunoglobulin (Ig)A1 in the serum appear to be the trigger for generation of glycan-specific IgG and IgA autoantibodies, resulting in the formation of circulating IgA immune complexes, which are pivotal to the development of nephritis. It remains unclear why there is an increase in poorly galactosylated IgA1 molecules in the serum in IgAN. One intriguing possibility is that this IgA is derived from displaced mucosal B cells, which have mis-homed from their mucosal induction sites to systemic sites, where they secrete polymeric, poorly galactosylated IgA directly into the circulation rather than onto mucosal surfaces. Lack of a clear appreciation of the origins of poorly galactosylated IgA1 and an incomplete understanding of immune complex formation have hampered development of specific therapeutic strategies to prevent mesangial IgA deposition. Clinicians have therefore been left to manage patients with generic therapies, mainly by control of blood pressure and renin-angiotensin blockade. A paucity of high-quality clinical trials has meant that evaluation of additional therapies, particularly immunosuppressive regimens, has been difficult and there remains a great deal of confusion over the optimum treatment of patients at high risk of progressive chronic kidney disease. PMID- 22318426 TI - Engineers are from PDMS-land, Biologists are from Polystyrenia. AB - As the integration of microfluidics into cell biology research proceeds at an ever-increasing pace, a critical question for those working at the interface of both disciplines is which device material to use for a given application. While PDMS and soft lithography methods offer the engineer rapid prototyping capabilities, PDMS as a material has characteristics that have known adverse effects on cell-based experiments. In contrast, while polystyrene (PS), the most commonly used thermoplastic for laboratory cultureware, has provided decades of grounded and validated research conclusions in cell behavior and function, PS as a material has posed significant challenges in microfabrication. These competing issues have forced microfluidics engineers and biologists to make compromises in how they approach specific research questions, and furthermore, have attenuated the impact of microfluidics on biological research. In this review, we provide a comparison of the attributes of PDMS and PS, and discuss reasons for their popularity in their respective fields. We provide a critical evaluation of the strengths and limitations of PDMS and PS in relation to the advancement and future impact on microfluidic cell-based studies and applications. We believe that engineers have a responsibility to overcome any challenges associated with microfabrication, whether with PS or other materials, and that engineers should provide options and solutions that assist biologists in their experimental design. Our goal is not to advocate for any specific material, but provide guidelines for researchers who desire to choose the most suitable material for their application, and suggest important research directions for engineers working at the interface between microfabrication technology and biological application. PMID- 22318427 TI - Presence of luminal neutrophil extracellular traps in atherosclerosis. PMID- 22318428 TI - How big is a Cp? Cycloheptatrienyl zirconium complexes with bulky cyclopentadienyl and indenyl ligands. AB - A combination of phase-transfer and traditional alkylation strategies has been employed to synthesise sterically encumbered 1,3-di(cyclohexyl) and 1,3-di(tert butyl) substituted indenes in multi-gram quantities. These indenyl ligands and sterically demanding alkyl cyclopentadienyl ligands have been used to prepare a series of [(eta(7)-C(7)H(7))Zr(eta(5)-L)] (L = Cp and Ind) complexes by straightforward salt metathesis between [(eta(7)-C(7)H(7))ZrCl(tmeda)] and the corresponding sodium indenide or cyclopentadienide. All of these Zr complexes have been characterized by elemental analysis, NMR spectroscopy and single crystal X-ray diffraction. The structural information derived from these studies was employed to evaluate the steric demand of these ligands in a realistic manner. PMID- 22318429 TI - Predictive power of "a minima" models in biology. AB - Many apparently complex mechanisms in biology, especially in embryology and molecular biology, can be explained easily by reasoning at the level of the "efficient cause" of the observed phenomenology: the mechanism can then be explained by a simple geometrical argument or a variational principle, leading to the solution of an optimization problem, for example, via the co-existence of a minimization and a maximization problem (a min-max principle). Passing from a microscopic (or cellular) level (optimal min-max solution of the simple mechanistic system) to the macroscopic level often involves an averaging effect (linked to the repetition of a large number of such microscopic systems with possible random choice of the parameters of each of them) that gives birth to a global functional feature (e.g. at the tissue level). We will illustrate these general principles by building in four different domains of application "a minima" models and showing the main properties of their solutions: (1) extraction of a minimal RNA structure functioning as the first "peptidic machine," a kind of ancestral ribosome; (2) study of a genetic regulatory network of Drosophila centred on Engrailed gene and expressing successively two genes inside a limit cycle; (3) study of a genetic network regulating neural activity and proliferation in mammals; and (4) study of a simple geometric model of epiboly in zebrafish. PMID- 22318430 TI - PD-L1 co-stimulation, ligand-induced TCR down-modulation and anti-tumor immunotherapy. AB - PD-1 engagement on the surface of effector T cells strongly suppresses their cytotoxic function, which constitutes a major obstacle for T cell-mediated anti tumor activities. Surprisingly, PD-1 is strongly upregulated in T cells, engaging its ligand PD-L1 during antigen presentation. However, our recent published data may provide an explanation for this apparent contradiction. PMID- 22318431 TI - Asymmetric homogeneous hydrogenations at scale. AB - Asymmetric hydrogenations are increasingly being used to introduce stereogenic centres into products used in the life sciences industries. There are a number of potential pitfalls when moving from a laboratory reaction to a manufacturing process, not least of which is safety. Time-to-market pressure leads to short development times, which in the past could be a large barrier for the implementation of catalytic steps; now there are new ways to minimise this problem. The potential problems associated with impurities and other methods that can shut down the hydrogenation reactions are highlighted in this critical review (353 references). PMID- 22318432 TI - Clinical practice: Contraception in adolescents. AB - In affluent societies, median age at menarche has dropped to below 13 years. Younger age at menarche is associated with earlier sexual activity. To avoid unintended teenage pregnancies, barriers to contraception provision must be kept low, i.e. availability without prescription or through a low-threshold prescription system, low-cost options and long-term prescriptions or easy refills. Since many adolescents are (over)concerned about side effects, these should be addressed. A gynaecological examination prior to prescription is no longer recommended. All effective reversible contraceptive methods are available to adolescents: user-based hormonal contraceptives, trimonthly depot medroxyprogesterone acetate (DMPA), and long-acting reversible contraception (LARC). User-based hormonal contraceptives carry a small absolute risk of venous thromboembolism (~4 per 10,000 patient-years), but the risk is more than tenfold higher among young women with an inherited clotting defect. DMPA reduces bone mineral accumulation, but this is a reversible effect; the metabolic risks, including weight gain and insulin resistance, appear to be greater. LARC, including intrauterine contraceptive devices and the progestogen-containing implant, is gaining popularity among teenagers; abnormal bleeding is the main side effect. Any effective contraceptive should preferably be combined with consistent condom use to prevent sexually transmitted infections ("the double Dutch"). PMID- 22318433 TI - Stability of plant defensive traits among populations in two Eucalyptus species under elevated carbon dioxide. AB - Plant secondary metabolites (PSMs) mediate a wide range of ecological interactions. Investigating the effect of environment on PSM production is important for our understanding of how plants will adapt to large scale environmental change, and the extended effects on communities and ecosystems. We explored the production of PSMs under elevated atmospheric carbon dioxide ([CO(2)]) in the species rich, ecologically and commercially important genus Eucalyptus. Seedlings from multiple Eucalyptus globulus and E. pauciflora populations were grown in common glasshouse gardens under elevated or ambient [CO(2)]. Variation in primary and secondary chemistry was determined as a function of genotype and treatment. There were clear population differences in PSM expression in each species. Elevated [CO(2)] did not affect concentrations of individual PSMs, total phenolics, condensed tannins or the total oil yield, and there was no population by [CO(2)] treatment interaction for any traits. Multivariate analysis revealed similar results with significant variation in concentrations of E. pauciflora oil components between populations. A [CO(2)] treatment effect was detected within populations but no interactions were found between elevated [CO(2)] and population. These eucalypt seedlings appear to be largely unresponsive to elevated [CO(2)], indicating stronger genetic than environmental (elevated [CO(2)]) control of expression of PSMs. PMID- 22318434 TI - Can the severity of menopausal symptoms be predicted? PMID- 22318435 TI - Health symptoms during midlife in relation to menopausal transition: British prospective cohort study. AB - OBJECTIVE: To characterise symptoms experienced by women during the transition into natural menopause, to classify women into distinct symptom profiles or trajectories, and to relate these profiles to sociodemographic factors and health behaviours. DESIGN: Nationally representative cohort study. SETTING: England, Scotland, and Wales. PARTICIPANTS: 695 women followed-up since birth in 1946 and annually from age 47 to 54 who experienced natural menopause and reported on 20 common health symptoms. MAIN OUTCOME MEASURE: Longitudinal profiles for reported bothersome symptoms. RESULTS: Of 20 individual symptoms, 18 formed into four stable symptom groups: psychological, somatic, vasomotor, and sexual discomfort. Using latent class analyses, all except the somatic group of symptoms showed a clear relation with the timing of menopause for some women. A small proportion of women (10%, n=63) had a severe psychological symptom profile that peaked at or in the year after menopause. For vasomotor symptoms, 14% of women (n=83) had the early severe profile that also peaked around early postmenopause and then declined noticeably; 11% (n=67) had the late severe profile of bothersome symptoms that increased rapidly in perimenopause and remained high for four years or more after menopause. Women were less likely to have a profile for severe vasomotor symptoms if they were from a non-manual social class (odds ratio 0.79, 95% confidence interval 0.57 to 1.01) or had degree level qualifications (0.37, 0.18 to 0.77). The 14% of women (n=85) who had the late severe profile for sexual discomfort showed a similar increase in symptoms until menopause, with symptoms persisting after menopause. Married women were more likely to have the late severe or late moderate profile than women of other marital status (2.40, 1.30 to 4.41). Four profiles each were identified for somatic symptoms (mild, moderate, severe, and very severe), although these did not vary by chronological age or age at menopause. CONCLUSION: Profiles for psychological, vasomotor, and sexual discomfort symptoms relative to age at menopause could help health professionals to tailor their advice for women with natural menopause. PMID- 22318436 TI - Investigating focal liver lesions. PMID- 22318437 TI - Would you like your telomeres tested? PMID- 22318438 TI - Hormone therapy for menopausal symptoms. PMID- 22318439 TI - Extreme measures: the history of breast cancer surgery. PMID- 22318440 TI - Interactions. PMID- 22318441 TI - Migrant healthcare: public health versus politics. PMID- 22318442 TI - Clinical commissioning groups and councils must have single process for commissioning services for elderly, say MPs. PMID- 22318443 TI - Expatriate surgeons have helped advance orthopaedic care in Africa. PMID- 22318444 TI - Continuity is never out of fashion. PMID- 22318445 TI - [Facial nerve disorders]. PMID- 22318446 TI - Endovascular treatment of infrarenal abdominal aortic lesions with or without common iliac artery involvement. AB - PURPOSE: To evaluate the results of stent placement for obstructive atherosclerotic aortic disease with or without involvement of the common iliac artery. MATERIALS AND METHODS: Forty patients had self-expanding stents primarily or after balloon dilatation in the abdominal aorta between January 2005 and May 2011. All patients had trouble walking. Follow-up examinations were performed with clinical visits; these included color Doppler ultrasonography and computed tomographic angiography. RESULTS: Technical, clinical, and hemodynamic success was achieved in all patients. None of the patients underwent reintervention during the follow-up period, which ranged from 3 months to 6 years (median 24 months). Nine complications occurred in six patients. Of the nine complications, four were distal thromboembolisms, which were successfully treated with catheter directed thrombolysis or anticoagulation therapy. CONCLUSION: Endovascular treatment of the obstructive aortic disease using self-expanding stents was safe and effective, with high technical success and long-term patency. Thromboembolic complications were high even though direct stenting was considered protective for thromboembolism formation. Particularly for infrarenal aortic stenosis, it can be recommended as the first-line treatment option for patients with obstructive atherosclerotic aortic disease. PMID- 22318447 TI - Changes in renal function following Roux-en-Y gastric bypass: a prospective study. AB - BACKGROUND: Studies of the impact of Roux-en-Y gastric bypass (RYGB) on renal function have shown mixed results. We constructed this prospective repeated measures controlled study to characterize this response and identify the best method of gauging renal function in this setting. METHODS: Clinical data, serum creatinine (SC), and 24-h urine were collected 1 week before and 6 months following RYGB. Glomerular filtration rate (GFR) was calculated utilizing the Modification of Diet in Renal Disease formula. Creatinine clearance (CCL) was measured as a 24-h collection (24 CCL) and calculated by the Cockcroft-Gault (CG) formula. RESULTS: The study population of 37 patients (81% women) had a mean age of 47 +/- 11 years, had mean BMI of 47.6 +/- 6.3 kg/m(2), and achieved a mean % excess weight loss (EWL) of 60.9 +/- 17.1%. SC decreased from 0.83 +/- 0.21 mg/dl to 0.72 +/- 0.16 mg/dl (p < 0.001) and mean GFR improved from 91.6 +/- 29.7 ml/min/1.73 m(2) to 104.9 +/- 23.5 ml/min/1.73 m(2) (p < 0.01). Preoperatively, CG significantly overestimated CCL when compared with 24 CCL (197.1 +/- 88.2 ml/min vs. 136.5 +/- 53.0 ml/min, p < 0.001). In all patients, improvement in 24 CCL correlated with EWL (r = 0.32) and %EWL (r = 0.16), and significantly correlated with decrease in BMI (r = 0.51, p < 0.005). In hypertensive patients, improvement in 24 CCL significantly correlated with EWL (r = 0.43, p < 0.05), %EWL (r = 0.40, p < 0.05), and decrease in BMI (r = 0.60, p < 0.001) and was negatively correlated with age (r = -0.45, p < 0.05). CONCLUSIONS: This study demonstrates that renal function improves following RYGB and is best identified by change in GFR. Improvement in 24 CCL is correlated with the EWL success of the patient, especially hypertensive patients. PMID- 22318448 TI - Heating Affects Structure, Enterocyte Adsorption and Signalling, As Well as Immunogenicity of the Peanut Allergen Ara h 2. AB - Previous studies have indicated that specific molecular properties of proteins may determine their allergenicity. Allergen interaction with epithelia as the first contact site could be decisive for a resulting immune response. We investigate here for the major peanut allergen Ara h 2 whether thermal processing results in structural changes which may impact the protein's molecular interactions with enterocytes, subsequent cellular signalling response, and immunogenicity.Ara h 2 was heat processed and analyzed in terms of patient IgE binding, structural alterations, interaction with human enterocytes and associated signalling as well as immunogenicity in a food allergy mouse model.Heating of Ara h 2 led to significantly enhanced binding to Caco-2/TC7 human intestinal epithelial cells. Structural analyses indicated that heating caused persistent structural changes and led to the formation of Ara h 2 oligomers in solution. Heated protein exhibited a significantly higher immunogenic potential in vivo as determined by IgG and IgE serum antibody levels as well as IL-2 and IL-6 release by splenocytes. In human Caco-2/TC7 cells, Ara h 2 incubation led to a response in immune- and stress signalling related pathway components at the RNA level, whereas heated allergen induced a stress-response only.We suggest from this peanut allergen example that food processing may change the molecular immunogenicity and modulate the interaction capacity of food allergens with the intestinal epithelium. Increased binding behaviour to enterocytes and initiation of signalling pathways could trigger the epimmunome and influence the sensitization capacity of food proteins. PMID- 22318449 TI - Molecular and cellular effects of oncogene cooperation in a genetically accurate AML mouse model. AB - Biallelic CEBPA mutations and FMS-like tyrosine kinase receptor 3 (FLT3) length mutations are frequently identified in human acute myeloid leukemia (AML) with normal cytogenetics. However, the molecular and cellular mechanisms of oncogene cooperation remain unclear because of a lack of disease models. We have generated an AML mouse model using knockin mouse strains to study cooperation of an internal tandem duplication (ITD) mutation in the Flt3 gene with commonly observed CCAAT/enhancer binding protein alpha (C/EBPalpha) mutations. This study provides evidence that FLT3 ITD cooperates in leukemogenesis by enhancing the generation of leukemia-initiating granulocyte-monocyte progenitors (GMPs) otherwise prevented by a block in differentiation and skewed lineage priming induced by biallelic C/EBPalpha mutations. These cellular changes are accompanied by an upregulation of hematopoietic stem cell and STAT5 target genes. By gene expression analysis in premalignant populations, we further show a role of FLT3 ITD in activating genes involved in survival/transformation and chemoresistance. Both multipotent progenitors and GMP cells contain the potential to induce AML similar to corresponding cells in human AML samples showing that this model resembles human disease. PMID- 22318450 TI - Efficient transduction of healthy and malignant plasma cells by lentiviral vectors pseudotyped with measles virus glycoproteins. AB - A lot of genes deregulated in malignant plasma cells (PCs) involved in multiple myeloma have been reported these last years. The expression of some of these genes is associated with poor survival. A critical step is to elucidate the biological mechanisms triggered by these gene products. Such studies are hampered by the difficulty to obtain malignant PCs and to genetically modify them. Usual lentiviral vectors (LVs) pseudotyped with vesicular stomatitis virus envelope glycoprotein poorly transduced healthy and malignant PCs. Here, we report that LVs pseudotyped with the hemagglutinin and fusion glycoproteins from the measles Edmonston strain (H/F-LVs) can efficiently and stably transduce healthy and primary malignant PCs, without modifying their main phenotypic characteristics. Both LV pseudotypes efficiently transduced human myeloma cell lines. Importantly, both healthy and malignant PCs expressed CD46 and SLAMF1/CD150 membrane proteins, which are critical receptors for binding and productive genetic modification by H/F-LVs. The ability to efficiently introduce and express a given gene into PCs opens the possibility to study in detail PC biology. PMID- 22318451 TI - Application of click chemistry to the production of DNA microarrays. AB - The copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction was applied as the novel method of DNA immobilization on a modified solid support. The CuAAC click reaction enables the covalent binding of DNA modified with pentynyl groups at its 5'-end to azide-loaded slides. Click microarrays were produced using this approach and successfully employed in biological/model experiments. PMID- 22318453 TI - Cortisol response to repeated psychosocial stress. AB - Psychosocial stress plays a major role in the etiology and the course of mental disorders that often show an altered activation of the hypothalamus-pituitary adrenal (HPA) axis. The Trier Social Stress Test (TSST) reliably activates the HPA axis and reflects real life stress exposure. However, habituation may confound the results of clinical trials that apply TSST. The present study investigates the cortisol response after repeated psychosocial stress induction with short-term and long-term intervals between repeated testing sessions. Forty one healthy subjects were exposed to the TSST four times with an interval of 24 h between the first and the second testing session (t1 and t2). The 3rd and the 4th testing session (t3 and t4) were also separated by a 24-hour interval whereas there were 10 weeks between t2 and t3. A significant decrease in the salivary cortisol responses was noticed from testing session t1 to t2 as well as from testing session t3 to t4. By contrast, there were no differences in the HPA axis reactivity between testing session t2 and t3. Our results demonstrated the habituation of the HPA axis to a standardized psychosocial stress test when testing was repeated after 24 h. By contrast, a renewed challenge with a ten-week interval in-between activated the HPA axis in a similar manner as before. It is suggested that studies designed to investigate the HPA axis activity under repeated psychosocial stress conditions should apply the TSST three times in order to separate habituation from intervention effects. PMID- 22318454 TI - Magnetic nanoparticles for the manipulation of proteins and cells. AB - In the rapidly developing areas of nanobiotechnology, magnetic nanoparticles (MNPs) are one type of the most well-established nanomaterials because of their biocompatibility and the potential applications as alternative contrast enhancing agents for magnetic resonance imaging (MRI). While the development of MNPs as alternative contrast agents for MRI application has moved quickly to testing in animal models and clinical trials, other applications of biofunctional MNPs have been explored extensively at the stage of qualitative or conceptual demonstration. In this critical review, we summarize the development of two straightforward applications of biofunctional MNPs--manipulating proteins and manipulating cells--in the last five years or so and hope to provide a relatively comprehensive assessment that may help the future developments. Specifically, we start with the examination of the strategy for the surface functionalization of MNPs because the applications of MNPs essentially depend on the molecular interactions between the functional molecules on the MNPs and the intended biological targets. Then, we discuss the use of MNPs for manipulating proteins since protein interactions are critical for biological functions. Afterwards, we evaluate the development of the use of MNPs to manipulate cells because the response of MNPs to a magnetic field offers a unique way to modulate cellular behavior in a non-contact or "remote" mode (i.e. the magnet exerts force on the cells without direct contact). Finally, we provide a perspective on the future directions and challenges in the development of MNPs for these two applications. By reviewing the examples of the design and applications of biofunctional MNPs, we hope that this article will provide a reference point for the future development of MNPs that address the present challenges and lead to new opportunities in nanomedicine and nanobiotechnology (137 references). PMID- 22318455 TI - Emotional states and future risk of venous thromboembolism: the Tromso Study. AB - Emotional states of depression and loneliness are reported to be associated with higher risk and optimism with lower risk of arterial cardiovascular disease (CVD) and death. The relation between emotional states and risk of venous thromboembolism (VTE) has not been explored previously. We aimed to investigate the associations between self-reported emotional states and risk of incident VTE in a population-based, prospective study. The frequency of feeling depressed, lonely and happy/optimistic were registered by self-administered questionnaires, along with major co-morbidities and lifestyle habits, in 25,964 subjects aged 25 96 years, enrolled in the Tromso Study in 1994-1995. Incident VTE-events were registered from the date of inclusion until September 1, 2007. There were 440 incident VTE-events during a median of 12.4 years of follow-up. Subjects who often felt depressed had 1.6-fold (95% CI:1.02-2.50) higher risk of VTE compared to those not depressed in analyses adjusted for other risk factors (age, sex , body mass index, oestrogens), lifestyle (smoking, alcohol consumption, educational level) and co-morbidities (diabetes, CVD, and cancer). Often feeling lonely was not associated with VTE. However, the incidence rate of VTE in subjects who concurrently felt often lonely and depressed was higher than for depression alone (age-and sex-adjusted incidence rate: 3.27 vs. 2.21). Oppositely, subjects who often felt happy/optimistic had 40% reduced risk of VTE (HR 0.60, 95% CI: 0.41-0.87). Our findings suggest that self-reported emotional states are associated with risk of VTE. Depressive feelings were associated with increased risk, while happiness/optimism was associated with reduced risk of VTE. PMID- 22318456 TI - Amino acid-mediated aldolase immobilisation for enhanced catalysis and thermostability. AB - To improve the properties of the immobilised 2-deoxy-D-ribose-5-phosphate aldolase (DERA), unreacted functional groups on support surface were blocked with amino acids. The relative activities of the immobilised enzyme were 144.7 and 141.9% when the post-immobilisation modification was done with Arg and Phe, respectively. The residual activity of immobilised DERA after heating at 60 degrees C for 120 min was 65.1% when Phe and Val were used as the blocking amino acids, a 2.0- and 2.87-fold increase over that of the immobilised (no post immobilisation blocking) and free DERA. Immobilised DERA maintained maximal activity in 2-deoxyribose-5-phosphate (DR5P) synthesis up to 600 mM of acetaldehyde, which was much higher than the amount of acetaldehyde tolerated by free enzyme (300 mM). This superior resistance to high acetaldehyde concentrations would accelerate the DR5P reaction by shifting the reaction equilibrium towards the product. The results from this study suggest that the novel immobilised DERA may be useful for industrial applications. PMID- 22318457 TI - Foreword in honour of a pioneer of medical law: Professor Margaret Brazier OBE QC FMedSci. PMID- 22318458 TI - Still hazy after all these years: the law regulating surrogacy. AB - In 1997, Margaret Brazier was asked by the then Government to chair a review of the laws regulating surrogacy. The subsequent Brazier Report made a number of recommendations, including the need for greater regulation and the tightening of 'expenses' payments. Fifteen years on, the limitations in the legal regulation of surrogacy have become increasingly clear. Yet, none of Brazier's recommendations have been adopted, despite the clear opportunity for revisiting the regulation of surrogacy offered during the passage of the Human Fertilisation and Embryology Act (2008). In this paper, we revisit the Brazier Report in the light of subsequent developments and assess to what extent its key findings remain salient. Brazier's recommendations will thus provide a jumping off point for a critical analysis of the current state of the law regarding surrogacy. PMID- 22318459 TI - Customer-centered careflow modeling based on guidelines. AB - In contemporary society, customer-centered health care, which stresses customer participation and long-term tailored care, is inevitably becoming a trend. Compared with the hospital or physician-centered healthcare process, the customer centered healthcare process requires more knowledge and modeling such a process is extremely complex. Thus, building a care process model for a special customer is cost prohibitive. In addition, during the execution of a care process model, the information system should have flexibility to modify the model so that it adapts to changes in the healthcare process. Therefore, supporting the process in a flexible, cost-effective way is a key challenge for information technology. To meet this challenge, first, we analyze various kinds of knowledge used in process modeling, illustrate their characteristics, and detail their roles and effects in careflow modeling. Secondly, we propose a methodology to manage a lifecycle of the healthcare process modeling, with which models could be built gradually with convenience and efficiency. In this lifecycle, different levels of process models are established based on the kinds of knowledge involved, and the diffusion strategy of these process models is designed. Thirdly, architecture and prototype of the system supporting the process modeling and its lifecycle are given. This careflow system also considers the compatibility of legacy systems and authority problems. Finally, an example is provided to demonstrate implementation of the careflow system. PMID- 22318460 TI - Tests enhance retention and transfer of spatial learning. AB - Many studies have reported that tests are beneficial for learning (e.g., Roediger & Karpicke, 2006a). However, the majority of studies on the testing effect have been limited to a combination of relatively simple verbal tasks and final tests that assessed memory for the same material that had originally been tested. The present study explored whether testing is beneficial for complex spatial memory and whether these benefits hold for both retention and transfer. After encoding a three-dimensional layout of objects presented in a virtual environment, participants completed a judgment-of-relative-direction (JRD) task in which they imagined standing at one object, facing a second object, and pointed to a third object from the imagined perspective. Some participants completed this task by relying on memory for the previously encoded layout (i.e., the test conditions), whereas for others the location of the third object was identified ahead of time, so that retrieval was not required (i.e., the study condition). On a final test assessing their JRD performance, the participants who learned through test outperformed those who learned through study. This was true even when corrective feedback was not provided on the initial JRD task and when the final test assessed memory from vantage points that had never been practiced during the initial JRD. PMID- 22318461 TI - Tuning redox potentials of bis(imino)pyridine cobalt complexes: an experimental and theoretical study involving solvent and ligand effects. AB - The structure and electrochemical properties of a series of bis(imino)pyridine Co(II) complexes (NNN)CoX(2) and [(NNN)(2)Co][PF(6)](2) (NNN = 2,6-bis[1-(4-R phenylimino)ethyl]pyridine, with R = CN, CF(3), H, CH(3), OCH(3), N(CH(3))(2); NNN = 2,6-bis[1-(2,6-(iPr)(2)-phenylimino)ethyl]pyridine and X = Cl, Br) were studied using a combination of electrochemical and theoretical methods. Cyclic voltammetry measurements and DFT/B3LYP calculations suggest that in solution (NNN)CoCl(2) complexes exist in equilibrium with disproportionation products [(NNN)(2)Co](2+) [CoCl(4)](2-) with the position of the equilibrium heavily influenced by both the solvent polarity and the steric and electronic properties of the bis(imino)pyridine ligands. In strong polar solvents (e.g., CH(3)CN or H(2)O) or with electron donating substituents (R = OCH(3) or N(CH(3))(2)) the equilibrium is shifted and only oxidation of the charged products [(NNN)(2)Co](2+) and [CoCl(4)](2-) is observed. Conversely, in nonpolar organic solvents such as CH(2)Cl(2) or with electron withdrawing substituents (R = CN or CF(3)), disproportionation is suppressed and oxidation of the (NNN)CoCl(2) complexes leads to 18e(-) Co(III) complexes stabilized by coordination of a solvent moiety. In addition, the [(NNN)(2)Co][PF(6)](2) complexes exhibit reversible Co(II/III) oxidation potentials that are strongly dependent on the electron withdrawing/donating nature of the N-aryl substituents, spanning nearly 750 mV in acetonitrile. The resulting insight on the regulation of redox properties of a series of bis(imino)pyridine cobalt(II) complexes should be particularly valuable to tune suitable conditions for reactivity. PMID- 22318462 TI - [The first clinical use of an Dynamic Registration Tool for Navigation in FESS]. AB - BACKGROUND: The effective register accuracy in an situs issues a challenge to the employment of instrument navigation in the ENT Surgery. The idea of the initially determined process Dynamic Registration Supply (DRS) is to improve the register accuracy by the automatic, and interoperability of the register. MATERIALS AND METHODS: The aim was to determine clinical use of DRS. Opto-electrical system Navigation Panel Unit, vs. 4.0.0 with the functionality DRS was used. Experiments were carried out on 95 patients who had so called FESS. The data of a control group were available to researchers. The measuring log includes among other things following parameters: retooling time, cutting-suture time, frequency of use of the navigated pointer, frequency of additional registration. RESULTS: At least once during the procedure DRS has been activated in 85 of 95 interventions (89.5). The time required increased by 15% accumulated 189 s per intervention. The most frequently used additional registration was in the region of sphenoid sinus. The surgeons underlined that out of 95 surveys in 75 cases the DRS rendered the instrument navigation more precise, while 1% of 93 cases considered this function as unwanted. CONCLUSION: The first clinical study for use of an automatic algorithm for recognition and reduction of faulty registration of a CT, navigation was successful. The findings suggest that by using automatic intraoperative registration DRS consisting inaccuracy can be reduced. In practice this means an efficient quality improvement of the Navigation. PMID- 22318463 TI - [The role of sex in voice restoration and emotional functioning after laryngectomy]. AB - BACKGROUND: Data on psychosocial factors of laryngectomized women is rare. All means of alaryngeal voice production sound male due to low fundamental frequency and roughness, which makes postlaryngectomy voice rehabilitation especially challenging to women. Aim of this study was to investigate whether women use alaryngeal speech more seldomly and therefore are more emotionally distressed. MATERIAL AND METHODS: In a cross-sectional multi-centred study 12 female and 138 male laryngectomees were interviewed. To identify risc factors on seldom use of alaryngeal speech and emotional functioning, logistic regression was used and odds ratios were adjusted to age, time since laryngectomy, physical functioning, social activity and feelings of stigmatization. RESULTS: Esophageal speech was used by 83% of the female and 57% of the male patients, prosthetic speech was used by 17% of the female and 20% of the male patients and electrolaryngeal speech was used by 17% of the female and 29% of the male patients. There was a higher risk for laryngectomees to be more emotionally distressed when feeling physically bad (OR=2,48; p=0,02) or having feelings of stigmatization (OR=3,94; p<=0,00). Besides more women tended to be socially active than men (83% vs. 54%; p=0,05). CONCLUSIONS: There was no influence of sex neither on use of alaryngeal speech nor on emotional functioning. Since there is evidence for a different psychosocial adjustment in laryngectomized men and women, more investigation including bigger sample sizes will be needed on this special issue. PMID- 22318464 TI - [Acalculia after a summer holiday]. PMID- 22318465 TI - [Registration strategies for the application of the navigation system Fiagon at the lateral scull base]. AB - OBJECTIVE: The aim of this study was to evaluate a new navigation system (Fiagon GmbH) at the lateral skull base. MATERIAL AND METHODS: We performed repeated measurements and registrations on titanium screws, which were attached to specific anatomical locations on 5 temporal bone specimens. The focus of the investigation is to determinate the Target Registration Error and a comparison of different registration methods. RESULTS: Use of the navigation system seems to be practicable at the lateral scull base. For a registration strategy with 3 onesided attached Fiducials the Target Registration Error is 0.8 mm on the surface of the mastoid and in the mastoid cavity. The measurements at the inner ear canal showed a mean deviation of greater than 1.6 mm. In the comparison of different registration methods the best results were found for registration on titanium screws attached on both sides of the head, followed by surface registration at the face including laterobasis followed by registration in the mastoid cavity only. CONCLUSION: The measured values correspond to our clinical expectations and can be used if the existing Target Registration Error is known and respected. An intra-operative imaging may allow the application of titanium screws for navigation (gold standard) within the same general anesthesia during surgery. PMID- 22318466 TI - Susceptibility of people with long term illness to depression and anxiety is not recognised, report says. PMID- 22318467 TI - Abstracts of the Sylvester O'Halloran Meeting. March 2-3, 2012. Limerick, Ireland. PMID- 22318468 TI - N-acetylcysteine reduces oxidative stress in sickle cell patients. AB - Oxidative stress is of importance in the pathophysiology of sickle cell disease (SCD). In this open label randomized pilot study the effects of oral N acetylcysteine (NAC) on phosphatidylserine (PS) expression as marker of cellular oxidative damage (primary end point), and markers of hemolysis, coagulation and endothelial activation and NAC tolerability (secondary end points) were studied. Eleven consecutive patients (ten homozygous [HbSS] sickle cell patients, one HbSbeta(0)-thalassemia patient) were randomly assigned to treatment with either 1,200 or 2,400 mg NAC daily during 6 weeks. The data indicate an increment in whole blood glutathione levels and a decrease in erythrocyte outer membrane phosphatidylserine exposure, plasma levels of advanced glycation end-products (AGEs) and cell-free hemoglobin after 6 weeks of NAC treatment in both dose groups. One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose. During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications. These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress. PMID- 22318469 TI - A qualitative study of heterosexual women's attempts to renegotiate sexual relationships in the context of severe sexual problems. AB - Previous qualitative research on women's sexual problems has documented the ways in which they can impact psychological well-being as well as women's close interpersonal relationships. However, little attention has been paid to the ways that women with sexual problems negotiate sexual contact in the context of a relationship where sexual activity has a central role. This article draws on qualitative data from in-depth interviews with 23 heterosexual women who experienced sexual desire loss or vulvar pain. The data were analyzed within a material-discursive framework and this identified the centrality of relational and broader social factors in women's sexual negotiation. Key findings included: avoiding potentially intimate situations; engaging in intercourse when it was painful or the women had no desire to; and mentally planning and preparing themselves for sex. Other sexual activities were almost always regarded as a prelude to intercourse, yet around half of the sample had adapted their sexual repertoire to compensate for an absence of intercourse. The implications for future research and treatment in the area of women's sexual problems are discussed. PMID- 22318470 TI - Severe methemoglobinemia and hemolytic anemia from aniline purchased as 2C-E (4 ethyl-2,5-dimethoxyphenethylamine), a recreational drug, on the Internet - Oregon, 2011. AB - In August 2011, two men in Oregon drank a liquid they believed to be 2C-E (4 ethyl-2,5-dimethoxyphenethylamine), a psychoactive stimulant used as a recreational drug, after purchasing it on the Internet. Fifteen minutes after ingestion, the men became cyanotic and subsequently were treated for refractory methemoglobinemia and hemolytic anemia. The Oregon Poison Center, Oregon Public Health Division, Drug Enforcement Administration (DEA), and Food and Drug Administration (FDA) jointly investigated to determine the cause of the poisoning and identify other cases. The Oregon Poison Center and Oregon Public Health Division promptly alerted health-care providers and public health agencies and searched for additional cases. DEA confiscated all product remaining in the men's possession, and FDA identified the substance as aniline, an industrial solvent known to cause methemoglobinemia. One patient reported purchasing the substance from the Internet site of a Chinese chemical company. No additional cases were identified by investigators. Purchase of chemicals from unregulated Internet sources poses a serious risk to purchasers from product contamination and substitution. PMID- 22318471 TI - CDC grand rounds: dietary sodium reduction - time for choice. AB - Excess dietary sodium is a major contributor to hypertension (high blood pressure) and a critical public health issue in the United States. Nearly one in three U.S. adults, or 68 million persons, has hypertension, and half of those do not have their condition under control. Hypertension is a major contributor to cardiovascular diseases, which are a leading cause of death, disability, and health-care costs in the United States. The average sodium intake among persons in the United States aged >=2 years is 3,266 mg/day (excluding table salt). Current dietary guidelines recommend that reducing consumption of sodium to <2,300 mg/day, and that blacks, persons aged >=51 years, and persons of any age with hypertension, diabetes, or chronic kidney disease (about half of the U.S. population and the majority of adults) further reduce intake to 1,500 mg/day. Regardless of age or sex, sodium intake by most U.S. residents considerably exceeds recommended levels. Reducing sodium intake to 2,300 mg/day potentially could prevent 11 million cases of hypertension and save billions of dollars in health-care expenditures; reducing sodium intake further would yield additional benefits. To achieve those reductions and help consumers make healthful choices, expanded educational efforts and monitoring of the sodium content of the food supply are needed. Increased availability of lower sodium products and reductions in the amount of sodium in foods served or sold in the marketplace also are needed. PMID- 22318472 TI - Vital signs: food categories contributing the most to sodium consumption - United States, 2007-2008. AB - BACKGROUND: Most of the U.S. population consumes sodium in excess of daily guidelines (<2,300 mg overall and 1,500 mg for specific populations). Excessive sodium consumption raises blood pressure, which is a major risk factor for heart disease and stroke, the nation's first and fourth leading causes of death. Identifying food categories contributing the most to daily sodium consumption can help reduction. METHODS: Population proportions of sodium consumption from specific food categories and sources were estimated among 7,227 participants aged >=2 years in the What We Eat in America, National Health and Nutrition Examination Survey, 2007-2008. RESULTS: Mean daily sodium consumption was 3,266 mg, excluding salt added at the table. Forty-four percent of sodium consumed came from 10 food categories: bread and rolls, cold cuts/cured meats, pizza, poultry, soups, sandwiches, cheese, pasta mixed dishes, meat mixed dishes, and savory snacks. For most of these categories, >70% of the sodium consumed came from foods obtained at a store. For pizza and poultry, respectively, 51% and 27% of sodium consumed came from foods obtained at fast food/pizza restaurants. Mean sodium consumption per calorie consumed was significantly greater for foods and beverages obtained from fast food/pizza or other restaurants versus stores. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Average sodium consumption is too high, reinforcing the importance of implementing strategies to reduce U.S. sodium intake. Nationwide, food manufacturers and restaurants can strive to reduce excess sodium added to foods before purchase. States and localities can implement policies to reduce sodium in foods served in institutional settings (e.g., schools, child care settings, and government cafeterias). Clinicians can counsel most patients to check food labels and select foods lower in sodium. PMID- 22318474 TI - Integrated three-dimensional filter separates nanoscale from microscale elements in a microfluidic chip. AB - We report on the integration of a size-based three-dimensional filter, with micrometre-sized pores, in a commercial microfluidic chip. The filter is fabricated inside an already sealed microfluidic channel using the unique capabilities of two-photon polymerization. This direct-write technique enables integration of the filter by post-processing in a chip that has been fabricated by standard technologies. The filter is located at the intersection of two channels in order to control the amount of flow passing through the filter. Tests with a suspension of 3 MUm polystyrene spheres in a Rhodamine 6G solution show that 100% of the spheres are stopped, while the fluorescent molecules are transmitted through the filter. We demonstrate operation up to a period of 25 minutes without any evidence of clogging. Preliminary validation of the device for plasma separation from whole blood is shown. Moreover, the filter can be cleaned and reused by reversing the flow. PMID- 22318475 TI - Non-viral infections in children after renal transplantation. AB - Renal transplantation has long been recognised as the gold standard treatment for children with end-stage renal failure. There has been an improvement over the years in patient and renal allograft survival because of improved immunosuppression, surgical techniques and living kidney donation. Despite reduced acute allograft rejection rates, non-viral infections continue to be a serious complication for paediatric renal transplant recipients (RTR). The risk of infections in RTR is determined by the pre-transplantation immunisation status, post-transplant exposure to potential pathogens and the amount of immunosuppression. The greatest risk of life-threatening and Cytomegalovirus infections is during the first 6 months post-transplant owing to a high immunosuppressive burden. The potential sources of bacterial infections are donor derived, transplant medium fluid, peritoneal and haemodialysis catheter and transplant ureteric stent. Urinary tract infections are frequent in patients with lower urinary tract dysfunction and can result in renal allograft damage. This review outlines the incidence, timing, risk factors, prevention and treatment of non-viral infections in paediatric RTR by critically reviewing current immunosuppressive regimens, their risk-benefit ratio in order to optimise renal allograft survival with reduced rates of rejection and infectious complications. PMID- 22318476 TI - Analyzing functional brain connectivity by means of commute times: a new approach and its application to track event-related dynamics. AB - There is growing interest in studying the association of functional connectivity patterns with particular cognitive tasks. The ability of graphs to encapsulate relational data has been exploited in many related studies, where functional networks (sketched by different neural synchrony estimators) are characterized by a rich repertoire of graph-related metrics. We introduce commute times (CTs) as an alternative way to capture the true interplay between the nodes of a functional connectivity graph (FCG). CT is a measure of the time taken for a random walk to setout and return between a pair of nodes on a graph. Its computation is considered here as a robust and accurate integration, over the FCG, of the individual pairwise measurements of functional coupling. To demonstrate the benefits from our approach, we attempted the characterization of time evolving connectivity patterns derived from EEG signals recorded while the subject was engaged in an eye-movement task. With respect to standard ways, which are currently employed to characterize connectivity, an improved detection of event-related dynamical changes is noticeable. CTs appear to be a promising technique for deriving temporal fingerprints of the brain's dynamic functional organization. PMID- 22318477 TI - Unsupervised segmentation and quantification of anatomical knee features: data from the Osteoarthritis Initiative. AB - This paper presents a fully automated method for segmenting articular knee cartilage and bone from in vivo 3-D dual echo steady state images. The magnetic resonance imaging (MRI) datasets were obtained from the Osteoarthritis Initiative (OAI) pilot study and include longitudinal images from controls and subjects with knee osteoarthritis (OA) scanned twice at each visit (baseline, 24 month). Initially, human experts segmented six MRI series. Five of the six resultant sets served as reference atlases for a multiatlas segmentation algorithm. The methodology created precise knee segmentations that were used to extract articular cartilage volume, surface area, and thickness as well as subchondral bone plate curvature. Comparison to manual segmentation showed Dice similarity coefficient (DSC) of 0.88 and 0.84 for the femoral and tibial cartilage. In OA subjects, thickness measurements showed test-retest precision ranging from 0.014 mm (0.6%) at the femur to 0.038 mm (1.6%) at the femoral trochlea. In the same population, the curvature test-retest precision ranged from 0.0005 mm(-1) (3.6%) at the femur to 0.0026 mm(-1) (11.7%) at the medial tibia. Thickness longitudinal changes showed OA Pearson correlation coefficient of 0.94 for the femur. In conclusion, the fully automated segmentation methodology produces reproducible cartilage volume, thickness, and shape measurements valuable for the study of OA progression. PMID- 22318478 TI - A weighted power framework for integrating multisource information: gene function prediction in yeast. AB - Predicting the functions of unannotated genes is one of the major challenges of biological investigation. In this study, we propose a weighted power scoring framework, called weighted power biological score (WPBS), for combining different biological data sources and predicting the function of some of the unclassified yeast Saccharomyces cerevisiae genes. The relative power and weight coefficients of different data sources, in the proposed score, are estimated systematically by utilizing functional annotations [yeast Gene Ontology (GO)-Slim: Process] of classified genes, available from Saccharomyces Genome Database. Genes are then clustered by applying k-medoids algorithm on WPBS, and functional categories of 334 unclassified genes are predicted using a P-value cutoff 1 *10(-5). The WPBS is available online at http://www.isical.ac.in/~ shubhra/WPBS/WPBS.html, where one can download WPBS, related files, and a MATLAB code to predict functions of unclassified genes. PMID- 22318479 TI - Noninvasive measurement of physiological signals on a modified home bathroom scale. AB - A commercial bathroom scale with both handlebar and footpad electrodes was modified to enable measurement of four physiological signals: the ballistocardiogram (BCG), electrocardiogram (ECG), lower body impedance plethysmogram (IPG), and lower body electromyogram (EMG). The BCG, which describes the reaction of the body to cardiac ejection of blood, was measured using the strain gauges in the scale. The ECG was detected using handlebar electrodes with a two-electrode amplifier. For the lower body IPG, the two electrodes under the subject's toes were driven with an ac current stimulus, and the resulting differential voltage across the heels was measured and demodulated synchronously with the source. The voltage signal from the same two footpad electrodes under the heels was passed through a passive low-pass filter network into another amplifier, and the output was the lower body EMG signal. The signals were measured from nine healthy subjects, and the average signal-to-noise ratio (SNR) while the subjects were standing still was estimated for the four signals as follows: BCG, 7.6 dB; ECG, 15.8 dB; IPG, 10.7 dB. During periods of motion, the decrease in SNR for the BCG signal was found to be correlated to the increase in rms power for the lower body EMG (r = 0.89, p <; 0.01). The EMG could, thus, be used to flag noise-corrupted segments of the BCG, increasing the measurement robustness. This setup could be used for monitoring the cardiovascular health of patients at home. PMID- 22318480 TI - Visualisation of biomechanical data to assist therapeutic rehabilitation. AB - PURPOSE: The biomechanics community have to date had limited success in communicating complex biomechanical data and analyses outside of their field. The authors have created an innovative prototype software tool to visualise objective dynamic movement data captured from older adults undertaking activities of daily living (ADLs). Evaluation of this tool has shown it to be a successful way of communicating the complexity of older adult mobility data in an accessible manner for non-biomechanical specialists and lay audiences(1,2). METHODS: A software tool was developed, which generates a 3D animated human 'stick figure', on which the biomechanical demands of ADLs are represented visually at the joints as a percentage of each individual's maximum capability using a continuous colour gradient from green at 0%, amber at 50%, through to red at 100% (Figure 1). The tool was evaluated using a qualitative methodology of interviews and focus groups, where older adults and professionals viewed a series of visualisations of dynamic movement data(3). RESULTS AND DISCUSSION: Analysis of focus group discussions facilitated by the visualizations revealed new kinds of dialogues about biomechanical issues. The method of visualising and presenting the data clearly enabled people without training in biomechanics, both professionals and lay older people, to access and interpret the biomechanical information, based on their background, knowledge of a field or their personal experience. Further, the common visual medium enabled the sharing of different insights without recourse to specialist terminology or knowledge. New kinds of dialogues occurred in focus groups between older people and professionals about their experiences, based on real understanding of where the mobility problems were occurring. New dialogues also emerged between professionals from a range of different disciplines, crucial for different aspects of the care, wellbeing or design of the built environment for older people. Neither of these would have been possible using current conventions of presenting biomechanical data. The visualisations also appear to allow a deeper understanding of the issues within professions, both in healthcare and in design. These findings have led to new research with five discrete yet complementary studies covering a range of clinical applications of this method for: i) mobility and exercise advice for the healthy older adult; ii) falls prevention; iii) rehabilitation of total knee replacement; iv) to enhance early mobilisation of acute stroke patients and v) to enhance biomechanical diagnosis and fitting of ankle foot orthoses (AFO) in late stage stroke. PMID- 22318481 TI - The role of intravascular ultrasound in the determination of progression and regression of coronary artery disease. AB - New imaging techniques have been used to examine surrogate markers of atherosclerotic burden to determine the effects of pharmacologic intervention. In this review, we discuss the role of intravascular ultrasound (IVUS) in the determination of progression and regression of coronary artery disease. Several methodologic issues are discussed (selection of segments to analyze, measurement error, high drop out rate, and optimal IVUS variables). Usefulness of new IVUS derived variables (plaque composition by radiofrequency analysis, deformability by palpography, and endothelial shear stress by three-dimensional coronary anatomy reconstructed from IVUS and angiography) will be determined. Based on comparisons between IVUS and clinical studies, IVUS variables seem to be a valid surrogate in studies using atorvastatin in patients with dyslipidemia. It remains unclear whether IVUS variables are valid surrogates for other drugs/diseases. As such, further studies are needed to determine whether IVUS can serve as an efficient surrogate for clinical events in coronary disease trials. PMID- 22318482 TI - [Characteristics of university students using stimulants for cognitive enhancement: a pilot study]. AB - OBJECTIVE: Little is known regarding characteristics of subjects using substances exclusively for the purpose of pharmacological neuroenhancement (PN). Aim of this pilot study was to characterize students in Germany who use methylphenidate (MPH) and/or amphetamines (AMPH) for PN. METHODS: Semi-structured interviews among 20 students who reported the use of MPH/AMPH for PN and 20 matched controls. RESULTS: Subjects using stimulants for PN had significant better knowledge about further illicit substances for PN than controls. Users of AMPH more frequently used further illicit substances for PN than MPH users. Regarding prescription substances for PN no difference was found between MPH and AMPH users. AMPH users predominantly used AMPH intranasally for PN purposes. Stimulant users for PN used illicit substances (not for PN) more frequently with significantly higher rates of diagnoses of substance misuse of alcohol and THC (no difference between AMPH and MPH users). CONCLUSIONS: Larger epidemiological studies are needed to elucidate the risk of misuse and addiction in subjects using stimulants for PN. PMID- 22318483 TI - [Info-pocket-guide as a contribution to the prevention of mental illnesses]. AB - OBJECTIVE: To assess how Info-Pocket-Guides (IPG) are judged as an overall concept, with specific consideration for their content and design in terms of a successful contribution to the prevention of mental illnesses. METHODS: Altogether, eight student focus groups were conducted and differentiated according to sex, age, and educational system. RESULTS: Mainly, the respondents consider the IPGs as an appealing design, as well as a convenient and well-liked source of information. Some amendments regarding the range of topics were suggested. CONCLUSIONS: While there were doubts on the direct benefit of IPGs for the affected person, they were considered highly valuable for relatives and friends. For the acceptance of IPGs, an age-appropriate and context-involving mediation was found decisive. PMID- 22318484 TI - Automatic detection of gadolinium-enhancing multiple sclerosis lesions in brain MRI using conditional random fields. AB - Gadolinium-enhancing lesions in brain magnetic resonance imaging of multiple sclerosis (MS) patients are of great interest since they are markers of disease activity. Identification of gadolinium-enhancing lesions is particularly challenging because the vast majority of enhancing voxels are associated with normal structures, particularly blood vessels. Furthermore, these lesions are typically small and in close proximity to vessels. In this paper, we present an automatic, probabilistic framework for segmentation of gadolinium-enhancing lesions in MS using conditional random fields. Our approach, through the integration of different components, encodes different information such as correspondence between the intensities and tissue labels, patterns in the labels, or patterns in the intensities. The proposed algorithm is evaluated on 80 multimodal clinical datasets acquired from relapsing-remitting MS patients in the context of multicenter clinical trials. The experimental results exhibit a sensitivity of 98% with a low false positive lesion count. The performance of the proposed algorithm is also compared to a logistic regression classifier, a support vector machine and a Markov random field approach. The results demonstrate superior performance of the proposed algorithm at successfully detecting all of the gadolinium-enhancing lesions while maintaining a low false positive lesion count. PMID- 22318485 TI - On the Mechanism of T cell receptor down-modulation and its physiological significance. AB - Effective, long-lasting immune responses largely depend upon T cell reponses. Antigen-specific T lymphocytes are activated and differentiate into effector T cells after antigen presentation by professional antigen presenting cells (APCs). However, T cell responses are tightly regulated to prevent T cell hyperactivation which may end up in autoimmune pathology. One of these regulatory mechanisms is ligand-induced TCR down-modulation, a process by which TCRs are removed from the T cell surface shortly after engagement with their cognate antigenic peptide associated to MHC molecules on the APC. TCR down-modulation is a complicated process. Here we briefly describe the three main models that attempt to clarify this mechanism in the context of T cell activation and function. PMID- 22318486 TI - [Amyloidosis of the heart]. AB - Amyloidosis is a heterogeneous group of diseases characterized by the pathological deposition of autologous proteins in an antiparallel beta-sheet confirmation forming non-branching linear fibrils of indefinite length and an approximate diameter of 10-12 nm. Cardiac amyloidosis is caused by deposits in the heart and may lead to cardiac arrhythmia and low output failure. Following the diagnosis, classification of the amyloid protein and evaluation of further organ involvement is mandatory. Treatment approaches are based on reduction of the production of amyloid precursor proteins. Standard heart failure treatment is usually not well tolerated and the underlying disease remains unaffected. Cardiac amyloidosis, especially of the light chain type, is associated with a poor outcome. The clinical picture is uncharacteristic, therefore correct diagnosis of cardiac amyloidosis is often delayed in many patients. Combination of clinical symptoms of different organ systems should alert the physician to the diagnosis of amyloidosis. PMID- 22318487 TI - [Histopathological aspects of pulmonary hypertension]. AB - In pulmonary hypertension there is a discrepancy between the dramatic but unspecific clinical presentation and the remodeling of mostly only limited segments of the vascular compartment of pulmonary parenchyma. Clinical diagnosis relies for the most part on invasive procedures, such as right heart catheterization. Therefore, morphology can provide a reliable etiopathogenetic classification only in close cooperation with the clinical partner disciplines involved. Moreover, the histopathological approach requires intimate knowledge of the vascular anatomy of the lungs and assessment of the parenchyma to be able to diagnose pulmonary hypertension and differentiate between the various types. PMID- 22318488 TI - Cultured senescent myoblasts derived from human vastus lateralis exhibit normal mitochondrial ATP synthesis capacities with correlating concomitant ROS production while whole cell ATP production is decreased. AB - The free radical theory of aging says that increased oxidative stress and mitochondrial dysfunction are associated with old age. In the present study we have investigated the effects of cellular senescence on muscle energetic by comparing mitochondrial content and function in cultured muscle satellite cells at early and late passage numbers. We show that cultured muscle satellite cells undergoing senescence express a reduced mitochondrial mass, decreased whole cell ATP level, normal to increased mitochondrial ATP production under ATP utilization, increased mitochondrial membrane potential and increased superoxide/mitochondrial mass and hydrogen peroxide/mitochondrial mass ratios. Moreover, the increased ROS production correlates with the corresponding mitochondrial ATP production. Thus, myotubes differentiated from human myoblasts undergoing senescence have a reduced mitochondrial content, but the existent mitochondria express normal to increased functional capabilities. The present data suggest that the origin of aging lies outside the mitochondria and that a malfunction in the cell might be preceding and initiating the increase of mitochondrial ATP synthesis and concomitant ROS production in the single mitochondrion in response to decreased mitochondrial mass and reduced extra mitochondrial energy supply. This then can lead to the increased damage of DNA, lipids and proteins of the mitochondria as postulated by the free radical theory of aging. PMID- 22318490 TI - Multiview face recognition: from TensorFace to V-TensorFace and K-TensorFace. AB - Face images under uncontrolled environments suffer from the changes of multiple factors such as camera view, illumination, expression, etc. Tensor analysis provides a way of analyzing the influence of different factors on facial variation. However, the TensorFace model creates a difficulty in representing the nonlinearity of view subspace. In this paper, to break this limitation, we present a view-manifold-based TensorFace (V-TensorFace), in which the latent view manifold preserves the local distances in the multiview face space. Moreover, a kernelized TensorFace (K-TensorFace) for multiview face recognition is proposed to preserve the structure of the latent manifold in the image space. Both methods provide a generative model that involves a continuous view manifold for unseen view representation. Most importantly, we propose a unified framework to generalize TensorFace, V-TensorFace, and K-TensorFace. Finally, an expectation maximization like algorithm is developed to estimate the identity and view parameters iteratively for a face image of an unknown/unseen view. The experiment on the PIE database shows the effectiveness of the manifold construction method. Extensive comparison experiments on Weizmann and Oriental Face databases for multiview face recognition demonstrate the superiority of the proposed V- and K TensorFace methods over the view-based principal component analysis and other state-of-the-art approaches for such purpose. PMID- 22318491 TI - Fast graph-based relaxed clustering for large data sets using minimal enclosing ball. AB - Although graph-based relaxed clustering (GRC) is one of the spectral clustering algorithms with straightforwardness and self-adaptability, it is sensitive to the parameters of the adopted similarity measure and also has high time complexity O(N(3)) which severely weakens its usefulness for large data sets. In order to overcome these shortcomings, after introducing certain constraints for GRC, an enhanced version of GRC [constrained GRC (CGRC)] is proposed to increase the robustness of GRC to the parameters of the adopted similarity measure, and accordingly, a novel algorithm called fast GRC (FGRC) based on CGRC is developed in this paper by using the core-set-based minimal enclosing ball approximation. A distinctive advantage of FGRC is that its asymptotic time complexity is linear with the data set size N. At the same time, FGRC also inherits the straightforwardness and self-adaptability from GRC, making the proposed FGRC a fast and effective clustering algorithm for large data sets. The advantages of FGRC are validated by various benchmarking and real data sets. PMID- 22318492 TI - Changes in antigen-specific T-cell number and function during oral desensitization in cow's milk allergy enabled with omalizumab. AB - Food allergy is a major public health problem, for which there is no effective treatment. We examined the immunological changes that occurred in a group of children with significant cow's milk allergy undergoing a novel and rapid high dose oral desensitization protocol enabled by treatment with omalizumab (anti immunoglobulin (Ig)E monoclonal antibodies). Within a week of treatment, the CD4(+) T-cell response to milk was nearly eliminated, suggesting anergy in, or deletion of, milk-specific CD4(+) T cells. Over the following 3 months while the subjects remained on high doses of daily oral milk, the CD4(+) T-cell response returned, characterized by a shift from interleukin-4 to interferon-gamma production. Desensitization was also associated with reduction in milk-specific IgE and a 15-fold increase in milk-specific IgG4. These studies suggest that high dose oral allergen desensitization may be associated with deletion of allergen specific T cells, without the apparent development of allergen-specific Foxp3(+) regulatory T cells. PMID- 22318493 TI - Oral tolerance to food protein. AB - Oral tolerance is the state of local and systemic immune unresponsiveness that is induced by oral administration of innocuous antigen such as food proteins. An analogous but more local process also regulates responses to commensal bacteria in the large intestine and, together, mucosally induced tolerance appears to prevent intestinal disorders such as food allergy, celiac disease, and inflammatory bowel diseases. Here we discuss the anatomical basis of antigen uptake and recognition in oral tolerance and highlight possible mechanisms underlying the immunosuppression. We propose a model of stepwise induction of oral tolerance in which specialized populations of mucosal dendritic cells and the unique microenvironment of draining mesenteric lymph nodes combine to generate regulatory T cells that undergo subsequent expansion in the small intestinal lamina propria. The local and systemic effects of these regulatory T cells prevent potentially dangerous hypersensitivity reactions to harmless antigens derived from the intestine and hence are crucial players in immune homeostasis. PMID- 22318494 TI - Mucosal correlates of isolated HIV semen shedding during effective antiretroviral therapy. AB - Effective antiretroviral therapy (ART) suppresses the blood HIV RNA viral load (VL) below the level of detection. However, some individuals intermittently shed HIV RNA in semen despite suppression of viremia, a phenomenon termed "isolated HIV semen shedding (IHS)". In a previously reported clinical study, we collected blood and semen samples from HIV-infected men for 6 months after ART initiation, and documented IHS at >=1 visit in almost half of the participants, independent of ART regimen or semen drug levels. We now report the mucosal immune associations of IHS in these men. Blood and semen plasma cytokine levels were assayed by multiplex enzyme-linked immunosorbent assay, T-cell populations were evaluated by flow cytometry in freshly isolated blood and semen mononuclear cells, and semen cytomegalovirus (CMV) DNA levels were measured by PCR. Although IHS was not associated with altered blood or semen cytokine levels, the phenomenon was associated with a transient, dramatic increase in CD4+ and CD8+ T cell activation that was restricted to the semen compartment. All participants were CMV infected, and although semen CMV reactivation was common despite ART, this was not associated with T-cell activation or IHS. Further elucidation of the causes of compartmentalized mucosal T-cell activation and IHS may have important public health implications. PMID- 22318495 TI - Cytosolic flagellin receptor NLRC4 protects mice against mucosal and systemic challenges. AB - Bacterial flagellin is a dominant innate immune activator of the intestine. Therefore, we examined the role of the intracellular flagellin receptor, NLRC4, in protecting the gut and/or driving inflammation. In accordance with NLRC4 acting through transcription-independent pathways, loss of NLRC4 did not reduce the rapid robust changes in intestinal gene expression induced by flagellin administration. Loss of NLRC4 did not alter basal intestinal homeostasis nor predispose mice to development of colitis upon administration of an anti interleukin (IL)-10R monoclonal antibody. However, epithelial injury induced by dextran sulfate sodium in mice lacking NLRC4 resulted in a more severe disease, indicating a role for NLRC4 in protecting the gut. Moreover, loss of NLRC4 resulted in increased mortality in response to flagellate, but not aflagellate Salmonella infection. Thus, despite not being involved in rapid intestinal gene remodeling upon detection of flagellin, NLRC4-mediated inflammasome activation results in production of IL-1beta and IL-18, two cytokines that protect mice from mucosal and systemic challenges. PMID- 22318496 TI - Lymphotoxin and the amazing technicolor circus of intestinal homeostasis. AB - Recently a new lymphocyte subset called innate lymphoid cells has emerged and it includes key producers of interleukin (IL)-17 and IL-22 in the mucosal environment. Using Citrobacter rodentium infection to deliver a pathogenic insult to the colon, two studies have revealed an underlying role for lymphotoxin-beta receptor signaling in the generation of IL-22 by these cells. This observation links a system well known for its ability to organize lymphoid microenvironments into a basic mucosal response. PMID- 22318497 TI - A distinct cytokine and chemokine profile at the genital mucosa is associated with HIV-1 protection among HIV-exposed seronegative commercial sex workers. AB - The predominance of HIV-1 sexual transmission requires a greater understanding of the interaction between HIV-1 and the mucosal immune system. The study of HIV-1 exposed seronegative (HESN) individuals serves as a model to identify the correlates of protection and to aid in microbicide development. A total of 22 cytokines/chemokines were analyzed at the systemic and mucosal compartments in 57 HESN, 51 HIV-1-negative, and 67 HIV-1-infected commercial sex workers from Nairobi, Kenya. HESN individuals had significantly lower expression of monokine induced by interferon-gamma (MIG), interferon-gamma-induced protein 10 (IP-10), and interleukin-1alpha (IL-1alpha) in their genital mucosa compared with controls. HESN cytokine expression also distinctly correlates with mucosal antiproteases, suggesting that HESN individuals have a unique pattern of mucosal chemokine/cytokine expression, which may result in reduced trafficking at the mucosa. These data support the immune quiescence model of protection, whereby lower T-cell activation/recruitment at the mucosal compartment reduces HIV-1 target cell numbers and is an important component of natural protection from HIV 1. PMID- 22318498 TI - In God and CAM we trust. Religious faith and use of complementary and alternative medicine (CAM) in a nationwide cohort of women treated for early breast cancer. AB - Turning to faith in God or a higher spiritual power is a common way of coping with life-threatening disease such as cancer. Little, however, is known about religious faith among cancer patients in secular societies. The present study aimed at exploring the prevalence of religious faith among Danish breast cancer patients and at identifying whether socio-demographic, pre-cancer health status, clinical, and health behavior characteristics, including their use of complementary and alternative medicine (CAM), were associated with their degree of faith. Information on faith in God or a higher spiritual power and use of CAM was provided by a nationwide sample of 3,128 recurrence-free Danish women who had received surgery for early-stage breast cancer 15-16 months earlier. Socio demographic, clinical, and health status variables were obtained from national longitudinal registries, and health behaviors had been assessed at 3-4 months post-surgery. Of the women, 47.3% reported a high degree of faith (unambiguous believers), 35.9% some degree of faith (ambiguous believers), while the remaining 16.8% were non-believers. Unambiguous believers were more likely than ambiguous believers to experience their faith as having a positive impact on their disease and their disease-related quality-of-life. When compared to non-believers, unambiguous believers were also older, had poorer physical function, and were more frequent users of CAM, and more inclined to believe that their use of CAM would have a beneficial influence on their cancer. Disease- and treatment-related variables were unrelated to faith. While overall religious faith appears equally prevalent among Danish and US breast cancer patients, the majority of Danish breast cancer patients experienced ambiguous faith, whereas the majority of US patients have been found to express unambiguous faith. Our results suggest that future studies may benefit from exploring the role of faith for health behaviors, adherence to conventional treatment, and impact upon quality of life. PMID- 22318499 TI - Hepatocyte growth factor: molecular biomarker and player in cardioprotection and cardiovascular regeneration. AB - The liver possesses impressive regenerative capacities. Grafts of embryonic liver explants and liver explant-conditioned media have been shown to enhance the mitotic activity of hepatocytes. Hepatocyte growth factor (HGF), also named scatter factor (SF), has been identified as a primary candidate in promoting and regulating liver regeneration. Although initially thought to be a liver-specific mitogen, HGF was later reported to have mitogenic, motogenic, morphogenic, and anti-apoptotic activities in various cell types. By promoting angiogenesis and inhibiting apoptosis, endogenous HGF may play an important role in cardioprotection as well as in the regeneration of endothelial cells and cardiomyocytes after myocardial infarction. Since serum concentration of HGF increases in the early phase of myocardial infarction and in heart failure, HGF may also play a key role as a prognostic and diagnostic biomarker of cardiovascular disease. Here we discuss the role of HGF as a biomarker and mediator in cardioprotection and cardiovascular regeneration. PMID- 22318500 TI - Low-complexity image processing for real-time detection of neonatal clonic seizures. AB - In this paper, we consider a novel low-complexity real-time image-processing based approach to the detection of neonatal clonic seizures. Our approach is based on the extraction, from a video of a newborn, of an average luminance signal representative of the body movements. Since clonic seizures are characterized by periodic movements of parts of the body (e.g., the limbs), by evaluating the periodicity of the extracted average luminance signal it is possible to detect the presence of a clonic seizure. The periodicity is investigated, through a hybrid autocorrelation-Yin estimation technique, on a per window basis, where a time window is defined as a sequence of consecutive video frames. While processing is first carried out on a single window basis, we extend our approach to interlaced windows. The performance of the proposed detection algorithm is investigated, in terms of sensitivity and specificity, through receiver operating characteristic curves, considering video recordings of newborns affected by neonatal seizures. PMID- 22318501 TI - On-chip molecular communication: analysis and design. AB - We consider a confined space molecular communication system, where molecules or information carrying particles are used to transfer information on a microfluidic chip. Considering that information-carrying particles can follow two main propagation schemes: passive transport, and active transport, it is not clear which achieves a better information transmission rate. Motivated by this problem, we compare and analyze both propagation schemes by deriving a set of analytical and mathematical tools to measure the achievable information rates of the on-chip molecular communication systems employing passive to active transport. We also use this toolbox to optimize design parameters such as the shape of the transmission area, to increase the information rate. Furthermore, the effect of separation distance between the transmitter and the receiver on information rate is examined under both propagation schemes, and a guidepost to design an optimal molecular communication setup and protocol is presented. PMID- 22318502 TI - Functional status and health-related quality of life among allogeneic transplant patients at hospital discharge: a comparison of sociodemographic, disease, and treatment characteristics. AB - PURPOSE: The purpose of this paper is to report the findings of a study of hematopoietic cell transplant patients, describing the needs of allogeneic transplant patients at the time of discharge in regard to their functional status, quality of life (QOL), and caregiver information and comparing these needs across a number of sociodemographic, disease, and treatment characteristics. The findings of this study are part of a larger mixed-methods study, representing one data time point of the larger study. METHODS: This paper will discuss the baseline data collected at the time of discharge for 282 allogeneic transplant patients, which include sociodemographic data combined with disease, treatment, functional status, and QOL data to present a comprehensive portrait of the transplant patient at discharge. RESULTS: Mean age was 48 years, males represented 52%, and 22% of the patients were Hispanic. The majority of the patients had acute leukemia (55%), were diagnosed within the last 3 years, and had matched unrelated (52%) transplants. The time from transplant to discharge averaged 30 days. Mean scores for QOL (scale = 1-10, with 10 = best QOL) included a low score of 5.7 for both psychological and social well-being, 6.3 for overall QOL, and 7.1 for both physical and spiritual well-being. Males had significantly higher QOL than females, as did non-Hispanics. Patients with Hodgkin's disease had significantly lower overall QOL scores. CONCLUSIONS: Our results highlight the physical, psychological, social, and spiritual challenges which present for patients and their caregivers at the time of hospital discharge following allogeneic transplant. PMID- 22318503 TI - A new selective fluorogenic probe for trivalent cations. AB - A new selective chromo-fluorogenic probe for Fe(3+), Cr(3+) and Al(3+) is reported. Detection limits are in the MUM range and the fluorogenic sensing ability could be observed by the naked eye when illuminated with UV-light. No response is observed with divalent cations. PMID- 22318504 TI - Epidemiology of obesity, the metabolic syndrome, and chronic kidney disease. AB - The prevalence of obesity and metabolic syndrome (MetS) has increased over the past several decades and is expected to continue to increase. Although the individual components of MetS have previously been associated with chronic kidney disease (CKD) and end-stage renal disease (ESRD), until recently there were few data on the relationship between MetS itself and incident CKD and ESRD. A recent meta-analysis demonstrated an association between MetS and CKD. When pooling 10 prospective cohort studies, MetS was associated with an increased odds ratio for an estimated glomerular filtration rate (eGFR) less than 60 mL/ min per 1.73 m2 (OR, 1.55; 95% CI, 1.34-1.80). Additionally, published data suggest an association between MetS and albuminuria. Evidence suggests that lifestyle modifications such as weight reduction, reduced dietary fat intake and cholesterol, and pharmacologic treatments may reduce the burden of MetS and thus the risk for CKD, albuminuria, and ESRD. PMID- 22318506 TI - Droplet microfluidics for high-throughput biological assays. AB - Droplet microfluidics offers significant advantages for performing high throughput screens and sensitive assays. Droplets allow sample volumes to be significantly reduced, leading to concomitant reductions in cost. Manipulation and measurement at kilohertz speeds enable up to 10(8) samples to be screened in one day. Compartmentalization in droplets increases assay sensitivity by increasing the effective concentration of rare species and decreasing the time required to reach detection thresholds. Droplet microfluidics combines these powerful features to enable currently inaccessible high-throughput screening applications, including single-cell and single-molecule assays. PMID- 22318507 TI - Iron toxicity in neurodegeneration. AB - Iron is an essential element for life on earth, participating in a plethora of cellular processes where one-electron transfer reactions are required. Its essentiality, coupled to its scarcity in aqueous oxidative environments, has compelled living organisms to develop mechanisms that ensure an adequate iron supply, at times with disregard to long-term deleterious effects derived from iron accumulation. However, iron is an intrinsic producer of reactive oxygen species, and increased levels of iron promote neurotoxicity because of hydroxyl radical formation, which results in glutathione consumption, protein aggregation, lipid peroxidation and nucleic acid modification. Neurons from brain areas sensitive to degeneration accumulate iron with age and thus are subjected to an ever increasing oxidative stress with the accompanying cellular damage. The ability of these neurons to survive depends on the adaptive mechanisms developed to cope with the increasing oxidative load. Here, we describe the chemical and thermodynamic peculiarities of iron chemistry in living matter, review the components of iron homeostasis in neurons and elaborate on the mechanisms by which iron homeostasis is lost in Parkinson's disease, Alzheimer's disease and other diseases in which iron accumulation has been demonstrated. PMID- 22318509 TI - Pre- and post-operative diffusion tensor imaging of the median nerve in carpal tunnel syndrome. AB - OBJECTIVES: To use pre- and post-operative diffusion tensor imaging (DTI) to monitor median nerve integrity in patients suffering from carpal tunnel syndrome (CTS). METHODS: Diffusivity and anisotropy images along the median nerve were compared among 12 patients, 12 age-matched and 12 young control subjects and correlated with electrophysiological neurography results. Slice-wise DTI parameter values were calculated to focus on local changes. RESULTS: Results of pre-operative patients and age-matched control subjects differed only in the distal nerve. Moreover, pre-operative patients differed significantly from young controls and post-operative patients. The main abnormalities were increased diffusivity and decreased anisotropy in the carpal tunnel and distal median nerve. Post-operative clinical improvement was reflected in diffusivity, but not in anisotropy. Slice-wise analysis showed high pre-operative diffusivity at the distal nerve. All groups had relatively large inter-subject variation in both diffusivity and anisotropy. CONCLUSIONS: DTI can provide information complementary to clinical examination, electrophysiological recordings and anatomical MRI of diseases and injuries of peripheral nerves. However, similar age-related changes in diffusivity and anisotropy may weaken DTI specificity. Slice-wise analysis is necessary for detection of local changes in nerve integrity. KEY POINTS: * Diffusion tensor magnetic resonance imaging provides information complementary to conventional diagnostic methods. * Age caused similar changes to diffusivity and anisotropy as carpal tunnel syndrome. * Post operative clinical improvement was reflected in diffusivity, but not in anisotropy. * Inter-subject variation in diffusivity and anisotropy was considerable. PMID- 22318508 TI - Physiologic implications of metal-ion transport by ZIP14 and ZIP8. AB - Zinc, iron, and manganese are essential trace elements that serve as catalytic or structural components of larger molecules that are indispensable for life. The three metal ions possess similar chemical properties and have been shown to compete for uptake in a variety of tissues, suggesting that they share common transport proteins. Two likely candidates are the recently identified transmembrane proteins ZIP14 and ZIP8, which have been shown to mediate the cellular uptake of a number of divalent metal ions including zinc, iron, manganese, and cadmium. Although knockout and transgenic mouse models are beginning to define the physiologic roles of ZIP14 and ZIP8 in the handling of zinc and cadmium, their roles in the metabolism of iron and manganese remain to be defined. Here we review similarities and differences in ZIP14 and ZIP8 in terms of structure, metal transport, tissue distribution, subcellular localization, and regulation. We also discuss potential roles of these proteins in the metabolism of zinc, iron, manganese, and cadmium as well as recent associations with human diseases. PMID- 22318510 TI - Predictive value for mortality of the double product at rest obtained by home blood pressure measurement: the Ohasama study. AB - BACKGROUND: To clarify whether the double product (DP) (product of systolic blood pressure (SBP) and pulse rate (PR)) at rest based on home blood pressure (HBP) measurement has prognostic value for mortality. METHODS: HBP data of 2,583 participants from a Japanese general population (40% men) >=35 years of age (mean, 59 years) without a history of cardiovascular disease (CVD) were obtained. The prognostic significance for a 1,000 mm Hg * beats/min elevation in the DP was determined by Cox proportional hazard regression analysis. The association between mortality and the DP was compared to that between mortality and the SBP or the PR using the likelihood ratio (LR) test. RESULTS: During a mean follow-up of 12.0 years, 454 total deaths, 153 CVD deaths (85 cardiac diseases, 68 strokes), and 301 non-CVD deaths occurred. The DP was positively and significantly associated with total, CVD, cardiac, stroke, and non-CVD mortality. The LR test showed that the DP was more strongly associated with total mortality, mortality from cardiac disease, and non-CVD than SBP. Similarly, the DP was more strongly associated with total death, CVD death, and death from stroke than PR. CONCLUSIONS: The home DP was significantly associated with mortality, and the LR test indicated that the association between the DP and mortality would be stronger than that between mortality and SBP or PR. These findings are preliminary, and further study is needed to confirm the usefulness of the DP in risk stratification. PMID- 22318511 TI - Global cardiovascular risk associated with hypertension and extent of treatment and control according to risk group. AB - BACKGROUND: Hypertension (HTN) confers increased cardiovascular disease (CVD) risk; however, the variation in risk and how treatment and control rates may differ according to extent of risk needs clarification. We examined CVD risk distribution and treatment and control patterns according to risk group. METHODS: We estimated 10-year Framingham global risk in 1,509 U.S. persons aged >=30 years from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 with HTN and the proportion of subjects in low (<10%), intermediate (10-20%), and high (>20%) risk groups, or with pre-existing CVD, or who otherwise had high cardiometabolic risk according to European Society of Hypertension (ESH) criteria (diabetes (DM), metabolic syndrome (MetS), stage 3 HTN, or 3 additional CVD risk factors). We also examined HTN treatment and control rates by risk group. RESULTS: From Framingham risk assessment, 24% of subjects were low risk, 21% intermediate risk, 23% high risk, and 32% had CVD. An additional 39% of low and 51% of intermediate risk subjects were at high or very high risk based on European criteria, for a total of 80% classified high risk or with CVD by either criterion. Treatment rates across Framingham risk groups ranged from 58 to 75%. HTN control rates were over 80% for lower risk persons, but under 50% for higher risk subjects. CONCLUSIONS: There is a wide variation in CVD risk in persons with HTN with control rates still suboptimal in higher risk subjects. Future guidelines should consider risk stratification combining shorter and longer-term risk assessment to best identify those who have the greatest CVD risk. PMID- 22318512 TI - Early treatment with olmesartan prevents juxtamedullary glomerular podocyte injury and the onset of microalbuminuria in type 2 diabetic rats. AB - BACKGROUND: Studies were performed to determine if early treatment with an angiotensin II (Ang II) receptor blocker (ARB), olmesartan, prevents the onset of microalbuminuria by attenuating glomerular podocyte injury in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with type 2 diabetes mellitus. METHODS: OLETF rats were treated with either a vehicle, olmesartan (10 mg/kg/day) or a combination of nonspecific vasodilators (hydralazine 15 mg/kg/day, hydrochlorothiazide 6 mg/kg/day, and reserpine 0.3 mg/kg/day; HHR) from the age of 7-25 weeks. RESULTS: OLETF rats were hypertensive and had microalbuminuria from 9 weeks of age. At 15 weeks, OLETF rats had higher Ang II levels in the kidney, larger glomerular desmin-staining areas (an index of podocyte injury), and lower gene expression of nephrin in juxtamedullary glomeruli, than nondiabetic Long-Evans Tokushima Otsuka (LETO) rats. At 25 weeks, OLETF rats showed overt albuminuria, and higher levels of Ang II in the kidney and larger glomerular desmin-staining areas in superficial and juxtamedullary glomeruli compared to LETO rats. Reductions in mRNA levels of nephrin were also observed in superficial and juxtamedullary glomeruli. Although olmesartan did not affect glucose metabolism, it decreased blood pressure and prevented the renal changes in OLETF rats. HHR treatment also reduced blood pressure, but did not affect the renal parameters. CONCLUSIONS: This study demonstrated that podocyte injury occurs in juxtamedullary glomeruli prior to superficial glomeruli in type 2 diabetic rats with microalbuminuria. Early treatment with an ARB may prevent the onset of albuminuria through its protective effects on juxtamedullary glomerular podocytes. PMID- 22318513 TI - Cardiovascular and cerebrovascular events pre- and post-earthquake of 6 April 2009: the Abruzzo's experience. AB - BACKGROUND: On 6 April 2009, an earthquake occurred in Abruzzo, a small region in the middle-east of Italy. Its chief town, L'Aquila, was the epicenter. We carried out an observational analysis to evaluate the potential association between the earthquake and the rate of cardiovascular and cerebrovascular admissions of the residents in the province of L'Aquila. METHODS: We used administrative discharge data, extracting all admissions made from 6 April to 31 July 2008 (pre-earthquake control period) or from 6 April to 31 July 2009 (post-earthquake period), assigned to diagnosis-related groups (DRGs) related to cardiovascular or cerebrovascular diseases. RESULTS: The overall number of hospitalizations for cardio- or cerebrovascular diseases by residents in L'Aquila before and after the earthquake was 10,833. In the whole region, the hospitalization rate was slightly lower in 2009 (-0.9%), whereas only in the local health unit (LHU) of L'Aquila it showed an increase by +13.2% (P < 0.01), essentially due to cardiovascular diseases (+21.9%) in elderly people (+26.9%; P < 0.01). The proportion of the main comorbidities in the admissions for cardiovascular diseases of the residents in L'Aquila significantly increased (P = 0.03), but no significant differences could be observed for each comorbidity separately. CONCLUSIONS: Our study supports previous findings of an association between earthquakes and an increase in cardiovascular diseases in the elderly. PMID- 22318514 TI - Dabigatran etexilate for stroke prevention in patients with atrial fibrillation: resolving uncertainties in routine practice. AB - Dabigatran etexilate is a new oral anticoagulant recently approved in Europe for the prevention of stroke or systemic embolism in adult patients with non-valvular atrial fibrillation (AF) and at least one risk factor for stroke. With a fast onset of action and a predictable anticoagulant effect obviating the need for coagulation monitoring, dabigatran etexilate offers practical advantages over vitamin K antagonists in clinical practice. However, clinicians may have questions about practical aspects of dabigatran etexilate use including monitoring anticoagulant efficacy, interruption for surgical or invasive procedures and management of bleeding. This review article aims to address these concerns and provide guidance on the use of dabigatran etexilate in special situations, such as acute coronary syndromes and cardiac revascularisation. In addition, cut-off values for different coagulation assay results associated with an increased risk of bleeding are given. PMID- 22318515 TI - Outgrowth of single oncogene-expressing cells from suppressive epithelial environments. AB - Tumorigenesis is a clonal evolution process that is initiated from single cells within otherwise histologically normal tissue. It is unclear how single, sporadic mutant cells that have sustained oncogenic alterations evolve within a tightly regulated tissue environment. Here we investigated the effects of inducing oncogene expression in single cells in organotypic mammary acini as a model to elucidate the processes by which oncogenic alterations initiate clonal progression from organized epithelial environments. Sporadic cells induced to overexpress oncogenes that specifically perturb cell-cycle checkpoints (for example, E7 from human papilloma virus 16, and cyclin D1), deregulate Myc transcription or activate AKT signalling remained quiescent within growth arrested acini. By contrast, single cells that overexpress ERBB2 initiated a cellular cascade involving cell translocation from the epithelial layer, as well as luminal outgrowth that is characteristic of neoplastic progression in early stage epithelial tumours. In addition, ERBB2-mediated cell translocation to the lumen was found to depend on extracellular-regulated kinase and matrix metalloproteinase activities, and genetic alterations that perturb local cell matrix adhesion drove cell translocation. We also provide evidence that luminal cell translocation may drive clonal selection by promoting either the death or the expansion of quiescent oncogene-expressing cells, depending on whether the pre-existing alterations allow anchorage-independent survival and growth. Our data show that the initial outgrowth of single oncogene-expressing cells from organized epithelial structures is a highly regulated process, and we propose that a cell translocation mechanism allows sporadic mutant cells to evade suppressive micro-environments and elicits clonal selection for survival and proliferative expansion outside the native niches of these cells. PMID- 22318516 TI - Climate change: Shrinking glaciers under scrutiny. PMID- 22318517 TI - Expression of tumour-specific antigens underlies cancer immunoediting. AB - Cancer immunoediting is a process by which immune cells, particularly lymphocytes of the adaptive immune system, protect the host from the development of cancer and alter tumour progression by driving the outgrowth of tumour cells with decreased sensitivity to immune attack. Carcinogen-induced mouse models of cancer have shown that primary tumour susceptibility is thereby enhanced in immune compromised mice, whereas the capacity for such tumours to grow after transplantation into wild-type mice is reduced. However, many questions about the process of cancer immunoediting remain unanswered, in part because of the known antigenic complexity and heterogeneity of carcinogen-induced tumours. Here we adapted a genetically engineered, autochthonous mouse model of sarcomagenesis to investigate the process of cancer immunoediting. This system allows us to monitor the onset and growth of immunogenic and non-immunogenic tumours induced in situ that harbour identical genetic and histopathological characteristics. By comparing the development of such tumours in immune-competent mice with their development in mice with broad immunodeficiency or specific antigenic tolerance, we show that recognition of tumour-specific antigens by lymphocytes is critical for immunoediting against sarcomas. Furthermore, primary sarcomas were edited to become less immunogenic through the selective outgrowth of cells that were able to escape T lymphocyte attack. Loss of tumour antigen expression or presentation on major histocompatibility complex I was necessary and sufficient for this immunoediting process to occur. These results highlight the importance of tumour specific-antigen expression in immune surveillance, and potentially, immunotherapy. PMID- 22318518 TI - Single-molecule imaging of DNA pairing by RecA reveals a three-dimensional homology search. AB - DNA breaks can be repaired with high fidelity by homologous recombination. A ubiquitous protein that is essential for this DNA template-directed repair is RecA. After resection of broken DNA to produce single-stranded DNA (ssDNA), RecA assembles on this ssDNA into a filament with the unique capacity to search and find DNA sequences in double-stranded DNA (dsDNA) that are homologous to the ssDNA. This homology search is vital to recombinational DNA repair, and results in homologous pairing and exchange of DNA strands. Homologous pairing involves DNA sequence-specific target location by the RecA-ssDNA complex. Despite decades of study, the mechanism of this enigmatic search process remains unknown. RecA is a DNA-dependent ATPase, but ATP hydrolysis is not required for DNA pairing and strand exchange, eliminating active search processes. Using dual optical trapping to manipulate DNA, and single-molecule fluorescence microscopy to image DNA pairing, we demonstrate that both the three-dimensional conformational state of the dsDNA target and the length of the homologous RecA-ssDNA filament have important roles in the homology search. We discovered that as the end-to-end distance of the target dsDNA molecule is increased, constraining the available three-dimensional (3D) conformations of the molecule, the rate of homologous pairing decreases. Conversely, when the length of the ssDNA in the nucleoprotein filament is increased, homology is found faster. We propose a model for the DNA homology search process termed 'intersegmental contact sampling', in which the intrinsic multivalent nature of the RecA nucleoprotein filament is used to search DNA sequence space within 3D domains of DNA, exploiting multiple weak contacts to rapidly search for homology. Our findings highlight the importance of the 3D conformational dynamics of DNA, reveal a previously unknown facet of the homology search, and provide insight into the mechanism of DNA target location by this member of a universal family of proteins. PMID- 22318519 TI - Recent contributions of glaciers and ice caps to sea level rise. AB - Glaciers and ice caps (GICs) are important contributors to present-day global mean sea level rise. Most previous global mass balance estimates for GICs rely on extrapolation of sparse mass balance measurements representing only a small fraction of the GIC area, leaving their overall contribution to sea level rise unclear. Here we show that GICs, excluding the Greenland and Antarctic peripheral GICs, lost mass at a rate of 148 +/- 30 Gt yr(-1) from January 2003 to December 2010, contributing 0.41 +/- 0.08 mm yr(-1) to sea level rise. Our results are based on a global, simultaneous inversion of monthly GRACE-derived satellite gravity fields, from which we calculate the mass change over all ice-covered regions greater in area than 100 km(2). The GIC rate for 2003-2010 is about 30 per cent smaller than the previous mass balance estimate that most closely matches our study period. The high mountains of Asia, in particular, show a mass loss of only 4 +/- 20 Gt yr(-1) for 2003-2010, compared with 47-55 Gt yr(-1) in previously published estimates. For completeness, we also estimate that the Greenland and Antarctic ice sheets, including their peripheral GICs, contributed 1.06 +/- 0.19 mm yr(-1) to sea level rise over the same time period. The total contribution to sea level rise from all ice-covered regions is thus 1.48 +/- 0.26 mm (-1), which agrees well with independent estimates of sea level rise originating from land ice loss and other terrestrial sources. PMID- 22318520 TI - Extrathymically generated regulatory T cells control mucosal TH2 inflammation. AB - A balance between pro- and anti-inflammatory mechanisms at mucosal interfaces, which are sites of constitutive exposure to microbes and non-microbial foreign substances, allows for efficient protection against pathogens yet prevents adverse inflammatory responses associated with allergy, asthma and intestinal inflammation. Regulatory T (T(reg)) cells prevent systemic and tissue-specific autoimmunity and inflammatory lesions at mucosal interfaces. These cells are generated in the thymus (tT(reg) cells) and in the periphery (induced (i)T(reg) cells), and their dual origin implies a division of labour between tT(reg) and iT(reg) cells in immune homeostasis. Here we show that a highly selective blockage in differentiation of iT(reg) cells in mice did not lead to unprovoked multi-organ autoimmunity, exacerbation of induced tissue-specific autoimmune pathology, or increased pro-inflammatory responses of T helper 1 (T(H)1) and T(H)17 cells. However, mice deficient in iT(reg) cells spontaneously developed pronounced T(H)2-type pathologies at mucosal sites--in the gastrointestinal tract and lungs--with hallmarks of allergic inflammation and asthma. Furthermore, iT(reg)-cell deficiency altered gut microbial communities. These results suggest that whereas T(reg) cells generated in the thymus appear sufficient for control of systemic and tissue-specific autoimmunity, extrathymic differentiation of T(reg) cells affects commensal microbiota composition and serves a distinct, essential function in restraint of allergic-type inflammation at mucosal interfaces. PMID- 22318521 TI - Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. AB - Cancer immunoediting, the process by which the immune system controls tumour outgrowth and shapes tumour immunogenicity, is comprised of three phases: elimination, equilibrium and escape. Although many immune components that participate in this process are known, its underlying mechanisms remain poorly defined. A central tenet of cancer immunoediting is that T-cell recognition of tumour antigens drives the immunological destruction or sculpting of a developing cancer. However, our current understanding of tumour antigens comes largely from analyses of cancers that develop in immunocompetent hosts and thus may have already been edited. Little is known about the antigens expressed in nascent tumour cells, whether they are sufficient to induce protective antitumour immune responses or whether their expression is modulated by the immune system. Here, using massively parallel sequencing, we characterize expressed mutations in highly immunogenic methylcholanthrene-induced sarcomas derived from immunodeficient Rag2(-/-) mice that phenotypically resemble nascent primary tumour cells. Using class I prediction algorithms, we identify mutant spectrin beta2 as a potential rejection antigen of the d42m1 sarcoma and validate this prediction by conventional antigen expression cloning and detection. We also demonstrate that cancer immunoediting of d42m1 occurs via a T-cell-dependent immunoselection process that promotes outgrowth of pre-existing tumour cell clones lacking highly antigenic mutant spectrin-beta2 and other potential strong antigens. These results demonstrate that the strong immunogenicity of an unedited tumour can be ascribed to expression of highly antigenic mutant proteins and show that outgrowth of tumour cells that lack these strong antigens via a T-cell dependent immunoselection process represents one mechanism of cancer immunoediting. PMID- 22318522 TI - Introduction to the special section: the anthropology of psychopharmaceuticals: cultural and pharmacological efficacies in context. PMID- 22318523 TI - Targeted therapy for biliary tract cancers. AB - Biliary tract cancers (BTCs) are a heterogeneous group of malignancies, with a historically poor prognosis as a whole. Until recently, the development of effective therapeutics was hampered by the relatively low incidence, heterogeneity in patients and tumors, and correspondingly poor clinical trial enrollments. With the publication of the landmark phase III ABC-02 trial demonstrating the superiority of gemcitabine and cisplatin combination chemotherapy, the landscape changed for the development of new agents. Despite this progress, there are currently no approved targeted agents for BTC. This review will focus on recent developments in targeted therapeutics, directed against several key signaling pathways in BTC, including epidermal growth factor receptor, angiogenesis, and the mitogen-activated protein kinase pathway. Data from recent phase I and II trials will be discussed, along with a preview of upcoming trials involving targeted therapies. PMID- 22318524 TI - [Current treatment of acute myeloid leukaemia in adults]. AB - Recent cytogenetical findings and novel molecular biology results of acute myeloid leukaemia have shed new lights of our understanding in the diagnosis and treatment of the disease. Acute myeloid leukaemia is not only represented by the wide variety of morphological and immunophenotypic diversity but also demonstrates cytogenetical and molecular biological heterogeneity of its own. It has an unfavorable prognosis, especially in the elderly. Overall survival of younger patients (<50-60 years) has increased in the past years due to high dose chemotherapy (daunorubicine, cytarabine). But in case of unfavorable prognostic factors (not only cytogenetical but also molecular biological characters of the disease), allogeneic stem cell transplantation is needed for successful overall outcome. Better understanding the biology of acute myeloid leukaemia could establish novel targeted therapies and help us eventually to cure the disease. PMID- 22318525 TI - [Physicians' workforce and the current impact of international migration in Hungary]. AB - After 1989, as a result of the free international migration, there were significant changes in the physicians' workforce of Hungary. Nevertheless, the real breakthrough happened only after 1 May, 2004, when Hungary joined the European Union. The last free market restrictions imposed by Austria and Germany (on the new member states who joined in 2004) were lifted on 1 May, 2011. AIMS: Since no scientific or comprehensive evaluation dealt with the physicians' recent migration after 2004, let alone the day-to-day mass media communication, this study presents and analyses the changes between 1 January, 2006 and 31 December, 2010. METHODS: Data were obtained from the health care administration and by the national demographic statistics. RESULTS: It is clearly indicated that Hungary lost about 3,900 physicians in the course of these 5 years. CONCLUSIONS: There is clear evidence of a disturbed workforce balance and it must be taken into account that without any measures a serious lack of doctors will emerge in the following 1-2 years. PMID- 22318526 TI - [Carbon/carbon implants in oral and maxillofacial surgery -- part 1]. AB - Over the past 20-30 years various carbon implant materials have become more interesting, because they are well accepted by the biological environment. The traditional carbon-based polymers give rise to many complications. The polymer complication may be eliminated through carbon fibres bound by pyrocarbon (carbon/carbon). AIM: The aim of this study is to present the long-term results of carbon/carbon implants. METHODS: Mandibular reconstruction was performed with pure (99.99%) carbon implants in 16 patients. Predominantly tumorous cases were included (10 malignant tumors, 4 large cystic lesions and 2 augmentative processes). RESULTS: Because the interventions had been performed 6-8 years before the last follow-up visit, the authors report long-term results. Of the 16 patients, the implants had to be removed earlier in 5 patients because of the defect that arose on the oral mucosa above the carbon plates. The most probable cause of this complication was the strain in the oral mucosa and disturbances in its blood supply (previous surgery, irradiated tissue, etc.). During the long term follow-up, plate fracture, loosening of screws, infection or inflammation around the carbon/carbon implants were not observed. After 8 years one carbon implant was substituted with an autogenous bone. CONCLUSIONS: The clinical conclusion is that if the soft part cover is appropriate, the carbon implants are cosmetically and functionally more suitable than titanium plates. The structural and chemical investigation of the removed implant will be published in the near future. PMID- 22318527 TI - [Enzyme replacement therapy for Gaucher disease introduced in late adulthood]. AB - Gaucher disease is the most prevalent lysosomal storage disorder caused by recessive mutation of the beta-glucocerebrosidase gene, which leads to massive lysosomal accumulation of glucocerebrosids especially in macrophages of bone marrow, liver and spleen. The most common presenting signs and symptoms are hepatosplenomegaly, bone pain, pathologic fractures, fatigue, bleeding tendency and recurrent infections. Regular enzyme replacement therapy which is available since 1992 in Hungary successfully reverses the symptoms of the disorder, including hematological abnormalities, bone infiltration and hepatosplenomegaly. Authors present here two cases diagnosed in late adulthood to emphasize the importance of early diagnosis and treatment. PMID- 22318528 TI - [A new designer drug: methylone related death]. AB - This report presents a fatal case related to the consumption of methylone, a relatively new cathinone type designer drug. A 16-year-old boy suddenly lost his consciousness in a party. Resuscitation had been continued for about 1.5 hours at the intensive care unit, but it was unsuccessful. His previous history included cardiac malformation detected at infancy and bronchial asthma had been diagnosed one year before his death. Signs of sudden cardiac death were observed during autopsy. Methylone intake was proved in blood and liver extract using gas chromatography/mass spectrometry; its concentration was 272 ng/ml in the blood, and 387 ng/g in the liver. Pathohistology revealed microvascular steatosis in the liver, which raised the possibility of chronic use of toxic substances. In addition, striated heart muscle damage was observed, which could be due to the use of an amphetamine-like substance. The authors presume that steatosis of the heart muscle, congenital heart disease and bronchial asthma could be predisposing factors for sudden cardiac death that occurred in the presence of relatively low levels of methylone. Access to various designer drugs is easy, fast and broad. Consequently, the potential abuse or overdose should be taken into consideration in the emergency practice. The use of "non-illicit" drugs does not require formal intervention by the authorities, but the medical service must alarm the stakeholders. PMID- 22318530 TI - The effect of time-of-day and Ramadan fasting on anaerobic performances. AB - This study was designed to assess the effects of Ramadan-intermittent-fasting (RIF) and time-of-day on muscle power and fatigue during the Wingate test. In a randomized design, 10 football players completed a Wingate test at 07:00 and 17:00 h on 3 different occasions: one week before Ramadan (BR), the second week of Ramadan (SWR) and the fourth week of Ramadan (ER). There was an interval of 36 h between any 2 successive tests. During the Wingate test, peak power (PP), mean power (MP) and the fatigue index (FI) were recorded. While PP, MP and FI were greater in the evening than in the morning during BR (p<0.001), these diurnal variations in muscle power disappeared during the month of Ramadan (i. e., SWR and ER) due to a significant decrease in PP and MP in the evening (p<0.001). However, the diurnal variation in FI when measured at 17:00 h increased during this month (p<0.001). In addition, ratings of perceived exertion and fatigue were higher in the evening during Ramadan in comparison with BR. These results suggest that Ramadan might modify the circadian rhythm of muscle power and fatigue during the Wingate test by decreasing power output and increasing muscle fatigue at the time of the acrophase. PMID- 22318531 TI - Motives for and barriers to physical activity in twin pairs discordant for leisure time physical activity for 30 years. AB - Long-term persistent physical activity is important in the prevention of chronic diseases, but a large number of people do not participate in physical activity to obtain health benefits. The purpose of this study was to examine the motives and perceived barriers to long-term engagement in leisure time physical activity. Same-sex twin pairs (N=16, mean age 60) discordant for physical activity over 30 years were identified from the Finnish Twin Cohort. We evaluated participants' physical activity motivation with the 73-item Recreational Exercise Motivation Measure and assessed barriers to physical activity with a 25-item questionnaire. The characteristics of physical activity motivation and perceived barriers between the active and inactive co-twins were analysed using paired tests. Motives related to the sub-dimensions of enjoyment and physical fitness and psychological state were the most important reasons for participation in physical activity among all the twin individuals analysed. The sub-dimensions mastery (p=0.018, Cohen's d=0.76), physical fitness (p=0.029, Cohen's d=0.69), and psychological state (p=0.039, Cohen's d=0.65) differed significantly between active and inactive co-twins. More than half of the participants reported no reasons for not being physically active. If reasons existed, participation in physical activity was deterred mostly by pain and various health problems. This study found no differences in perceived barriers between active and inactive co twins. We conclude from our results that the main factors promoting persistent leisure time physical activity were participants' wish to improve or maintain their physical skills or techniques, a feeling that exercise would improve their mental and physical health and that they found the activity enjoyable. This study helps us understand the importance of the role of motives and the minor role of perceived barriers for engagement in persistent physical activity. PMID- 22318533 TI - Controlling the growth morphology of carbon nanotubes: from suspended bridges to upright forests. AB - We have developed two strategies to produce carbon nanotubes (CNTs) from low density surface growth to high-density forest growth. We have demonstrated that by introducing a C(2)H(2) pulse at the beginning of the growth, where methane is still used as the main carbon feeding gas, the growth tendency of CNTs can be changed and the resulting growth morphology will vary from surface growth to forest growth. Similarly, the growth morphology can be changed when the growth temperature is raised. The further characterization via Raman spectroscopy indicates that an increasing C(2)H(2) pulse time will lead to a rise of the D peak for as-grown CNTs, due to the formation of more multi-walled CNTs and the amorphous carbon contamination introduced by extra C(2)H(2), while a high growth temperature tends to produce high-quality CNTs and to reduce the amorphous carbon contamination. Furthermore, by appropriately adjusting the growth temperature and controlling the C(2)H(2) pulse time, we have managed to produce both suspended CNT bridges and upright forests within a single growth procedure and to form suspended pristine CNT transistors with a relatively high yield. In addition, the electrical properties of these CNT nanostructures have been investigated by electrical transport and scanning photocurrent measurements. PMID- 22318538 TI - Neurodiagnostic techniques in neonatal critical care. AB - This article reviews recent advances in the neurodiagnostic tools available to clinicians practicing in neonatal critical care. The advent of induced mild hypothermia for acute neonatal hypoxic-ischemic encephalopathy in 2005 has been responsible for renewed urgency in the development of precise and reliable neonatal neurodiagnostic techniques. Traditional evaluations of bedside head ultrasounds, head computed tomography scans, and routine electroencephalograms (EEGs) have been upgraded in most tertiary pediatric centers to incorporate protocols for MRI, continuous EEG monitoring with remote bedside access, amplitude-integrated EEG, and near-infrared spectroscopy. Meanwhile, recent studies supporting the association between placental pathology and neonatal brain injury highlight the need for closer examination of the placenta in the neurodiagnostic evaluation of the acutely ill newborn. As the pursuit of more effective neuroprotection moves into the "hypothermia plus" era, the identification, evaluation, and treatment of the neurologically affected newborn in the neonatal intensive care unit has increasing significance. PMID- 22318539 TI - Preferential control of induced regulatory T cell homeostasis via a Bim/Bcl-2 axis. AB - Apoptosis has an essential role in controlling T cell homeostasis, especially during the contraction phase of an immune response. However, its contribution to the balance between effector and regulatory populations remains unclear. We found that Rag1(-/-) hosts repopulated with Bim(-/-) conventional CD4(+) T cells (Tconv) resulted in a larger induced regulatory T cell (iTreg) population than mice given wild-type (WT) Tconv. This appears to be due to an increased survival advantage of iTregs compared with activated Tconv in the absence of Bim. Downregulation of Bcl-2 expression and upregulation of Bim expression were more dramatic in WT iTregs than activated Tconv in the absence of IL-2 in vitro. The iTregs generated following Tconv reconstitution of Rag1(-/-) hosts exhibited lower Bcl-2 expression and higher Bim/Bcl-2 ratio than Tconv, which indicates that iTregs were in an apoptosis-prone state in vivo. A significant proportion of the peripheral iTreg pool exhibits low Bcl-2 expression indicating increased sensitivity to apoptosis, which may be a general characteristic of certain Treg subpopulations. In summary, our data suggest that iTregs and Tconv differ in their sensitivity to apoptotic stimuli due to their altered ratio of Bim/Bcl-2 expression. Modulating the apoptosis pathway may provide novel therapeutic approaches to alter the balance between effector T cells and Tregs. PMID- 22318540 TI - Inhibition of Casein kinase-2 induces p53-dependent cell cycle arrest and sensitizes glioblastoma cells to tumor necrosis factor (TNFalpha)-induced apoptosis through SIRT1 inhibition. AB - Glioblastoma multiforme (GBM) are resistant to TNFalpha-induced apoptosis and blockade of TNFalpha-induced NF-kappaB activation sensitizes glioma cells to apoptosis. As Casein kinase-2 (CK2) induces aberrant NF-kappaB activation and as we observed elevated CK2 levels in GBM tumors, we investigated the potential of CK2 inhibitors (CK2-Is) - DRB and Apigenin in sensitizing glioma cells to TNFalpha-induced apoptosis. CK2-Is and CK2 small interfering RNA (siRNA) reduced glioma cell viability, inhibited TNFalpha-mediated NF-kappaB activation, and sensitized cell to TNFalpha-induced apoptosis. Importantly, CK2-Is activated p53 function in wild-type but not in p53 mutant cells. Activation of p53 function involved its increased transcriptional activation, DNA-binding ability, increased expression of p53 target genes associated with cell cycle progression and apoptosis. Moreover, CK2-Is decreased telomerase activity and increased senescence in a p53-dependent manner. Apoptotic gene profiling indicated that CK2 Is differentially affect p53 and TNFalpha targets in p53 wild-type and mutant glioma cells. CK2-I decreased MDM2-p53 association and p53 ubiquitination to enhance p53 levels. Interestingly, CK2-Is downregulated SIRT1 activity and over expression of SIRT1 decreased p53 transcriptional activity and rescued cells from CK2-I-induced apoptosis. This ability of CK2-Is to sensitize glioma to TNFalpha induced death via multiple mechanisms involving abrogation of NF-kappaB activation, reactivation of wild-type p53 function and SIRT1 inhibition warrants investigation. PMID- 22318541 TI - Aortic annulus dimension assessment by computed tomography for transcatheter aortic valve implantation: differences between systole and diastole. AB - Accurate assessment of aortic annular dimensions is essential for successful transcatheter aortic valve implantation (TAVI). Annular dimensions are conventionally measured in mid-systole by multidetector computed tomography (MDCT), echocardiography and angiography. Significant differences in systolic and diastolic aortic annular dimensions have been demonstrated in cohorts without aortic stenosis (AS), but it is unknown whether similar dynamic variation in annular dimensions exists in patients with severe calcific AS in whom aortic compliance is likely to be substantially reduced. We investigated the variation in aortic annular dimensions between systole and diastole in patients with severe calcific AS. Patients with severe calcific AS referred for TAVI were evaluated by 128-slice MDCT. Aortic annular diameter was measured during diastole and systole in the modified coronal, modified sagittal, and basal ring planes (maximal, minimal and mean diameters). Differences between systole and diastole were analysed by paired t test. Fifty-nine patients were included in the analysis. Three of the five aortic dimensions measured increased significantly during systole. The largest change was a 0.75 mm (3.4%) mean increase in the minimal diameter of the basal ring during systole (p = 0.004). This corresponds closely to the modified sagittal view, which also increased by mean 0.42 mm (1.9%) during systole (p = 0.008). There was no significant change in the maximal diameter of the basal ring or the modified coronal view during systole (p > 0.05). There is a small magnitude but statistically significant difference in aortic annulus dimensions of patients with severe AS referred for TAVI when measured in diastole and systole. This small difference is unlikely to alter clinical decisions regarding prosthesis size or suitability for TAVI. PMID- 22318542 TI - Evidence for prospective ECG-triggering coronary CT angiography in routine practice. PMID- 22318543 TI - Chirality induction in metal-induced achiral polythiophene aggregates assisted by optically active amines and polythiophene. AB - A regioregular achiral polythiophene bearing oxazoline pendant groups formed a unique optically active metal-induced supramolecular aggregate upon complexation with chiral amines or in the presence of a chiral polythiophene in a good solvent for the polymers, thus showing an induced circular dichroism. PMID- 22318544 TI - Ectopic expression of glucagon receptor in skeletal muscles improves glucose homeostasis in a mouse model of diabetes. AB - AIMS/HYPOTHESIS: Excessive secretion of glucagon partially contributes to the development of diabetic hyperglycaemia. However, complete blocking of glucagon action will lead to adverse effects, since glucagon exerts certain beneficial effects via its receptor in many organs. We aimed to study the effects of a 'decoy receptor' for circulating glucagon on modulating beta cell function and glucose homeostasis in mice by over-producing the glucagon receptor (GCGR) in skeletal muscles. METHODS: We generated transgenic mice in which the expression of Gcgr is driven by the muscle specific creatine kinase (Mck) promoter, and assessed the effects of glucagon on the modulation of glucose homeostasis under conditions of extremes of glucose influx or efflux. RESULTS: Mck/Gcgr mice showed increased circulating levels of glucagon and insulin, resulting in an unchanged ratio of glucagon-to-insulin. The levels of hepatic glucose-6-phosphatase (G6PC) and fructose-1,6-bisphosphatase (F1,6P2ase) were significantly decreased, whereas the phosphorylation level of pancreatic cAMP-response-element-binding-protein (CREB) was significantly increased in these transgenic mice. Under basal conditions, the mice displayed normal blood glucose levels and unchanged glucose tolerance and insulin sensitivity when compared with their age-matched wild-type (WT) littermates. However, following multiple low-dose streptozotocin injections, Mck/Gcgr mice exhibited a delay in the onset of hyperglycaemia compared with the WT controls. This was associated with preserved beta cell mass and beta cell secretory capacity in response to glucose challenge. CONCLUSIONS/INTERPRETATION: We suggest that mild and chronic hyperglucagonaemia, through a strategy involving neutralising peripheral glucagon action, provides beneficial effects on beta cell function and glucose homeostasis. Mck/Gcgr mice thus represent a novel mouse model for studying the physiological effects of glucagon. PMID- 22318545 TI - Inter and intra-ethnic differences in the distribution of the molecular variants of TPMT, UGT1A1 and MDR1 genes in the South Indian population. AB - Molecular variants of polymorphic drug metabolizing enzymes and drug transporters are attributed to differences in individual's therapeutic response and drug toxicity in different populations. We sought to determine the genotype and allele frequencies of polymorphisms for major phase II drug-metabolizing enzymes (TPMT, UGT1A1) and drug transporter (MDR1) in South Indians. Allelic variants of TPMT (*2,*3A,*3B,*3C & *8), UGT1A1 (TA)6>7 and MDR1 (2677G>T/A & 3435C>T) were evaluated in 450-608 healthy South Indian subjects. Genomic DNA was extracted by phenol-chloroform method and genotype was determined by PCR-RFLP, qRT-PCR, allele specific PCR, direct sequencing and SNaPshot techniques. The frequency distributions of TPMT, UGT1A1 and MDR1 gene polymorphisms were compared between the individual 4 South Indian populations viz., Tamilian, Kannadiga, Andhrite and Keralite. The combined frequency distribution of the South Indian populations together, was also compared with that of other major populations. The allele frequencies of TPMT*3C, UGT1A1 (TA)7, MDR1 2677T, 2677A and 3435T were 1.2, 39.8, 60.3, 3.7, and 61.6% respectively. The other variant alleles such as TPMT*2, *3A, *3B and *8 were not identified in the South Indian population. Sub-population analysis showed that the distribution of UGT1A1 (TA)6>7 and MDR1 allelic variants differed between the four ethnic groups. However, the frequencies of TPMT*3C allele were similar in the four South Indian populations. The distribution of TPMT, UGT1A1 and MDR1 gene polymorphisms of the South Indian population was significantly different from other populations. PMID- 22318546 TI - PDTC attenuate LPS-induced kidney injury in systemic lupus erythematosus-prone MRL/lpr mice. AB - Lipopolysaccharide (LPS) from bacteria can accelerate and exacerbate lupus nephritis (LN) and induce infiltrating inflammatory cells in kidney in animal models. Pyrrolidine dithiocarbamate (PDTC) is known to exert anti-inflammatory effects. Monocyte chemoattractant protein-1(MCP-1) is upregulated by various stimuli, including LPS, high glucose, and hyperosmolality. However, the molecular mechanisms of transcriptional regulation of the MCP-1 protein expression with LPS are poorly understood. Expression of MCP-1 was examined by western blot and enzyme-linked immunosorbent assay, respectively. The activity of nuclear factor (NF)-kappaB was measured by western blot. These mice have uncontrolled proliferation of T cells, an impaired response to T cell mitogen and produce autoantibodies against nuclear antigens, including DNA. We found that after LPS treatment for 14 weeks, LPS increased MCP-1 protein expression in kidney, which was significantly suppressed by antioxidant PDTC. The expression of NF-kappaB, pERK, pJNK and MCP-1 were increased, pp38 expression was decreased significantly, concomitantly with sera anti-dsDNA, MCP-1 and the acceleration of severity of autoimmune kidney injury. LPS induce markedly neutrophil infiltration in the glomerulus, especially around the mesangial region. PDTC reduced the number of infiltrating inflammatory cells and severity of kidney injury via inhibiting NF kappaB and p38 MAPK activity. They also markedly prevented LPS-induced pJNK and MCP-1. Therefore, MCP-1 may be responsible for the recruitment and activation of leukocytes in diseased kidneys in female MRL/lpr mice. In this study, the long term administration of PDTC had impacts on the prevention of end-stage organ damage induced by LPS treated. We demonstrated that PDTC inhibited LPS-induced monocyte migration and attenuated LPS-induced p38 MAPK activation. Based on these data we infer that PDTC inhibits LPS-induced MCP-1 expression, secretion and function through inhibition of NF-kappaB and p38 MAPK activity. Our study suggests that MAPK is an important therapeutic target of monocyte recruitment and accumulation within the glomerulus in inflammatory renal disease. These results suggest that PDTC protects against kidney inflammation of SLE at least in part via NF-kappaB and MAPK signaling pathways induction, and that inhibitory action on anti-dsDNA may be associated with the protective mechanism of PDTC. In summary, PDTC pretreatment attenuates LPS-induced kidney injury in female MRL/lpr mice through regulating NF-kappaB and MAPK signaling pathways. Our results indicate that LPS induces MCP-1 mainly through activating NF-kappaB and its downstream MAPK, and that such effect was inhibited by PDTC, suggesting the efficacy of PDTC in preventing kidney fibrosis in lupus-prone mice. Therefore, appropriate inhibition of NF-kappaB activation may attenuate the kidney injury in lupus-prone mice. PMID- 22318547 TI - Analysis of expressed sequence tags from grapevine flower and fruit and development of simple sequence repeat markers. AB - A total of 6,230 EST sequences were produced from 7,561 clones in a cDNA library generated from grapevine (Vitis vinifera cv. 'Summer Black') flower and fruit tissues in this study. After cluster and assembly analysis of the datasets, 3,582 unigenes (GenBank accession numbers GW836604-GW840185) were established, among which 381 were new grapevine EST sequences. Out of the 381 new ESTs, 289 could be mapped on the 19 grapevine chromosomes. 913 unique ESTs with known or putative functions were assigned to 11 putative cellular roles. 540 potentially workable grapevine EST-SSRs were developed from 3,582 unigenes and about 42.6% of these unigenes were identified as true-to-type SSR loci and could amplify polymorphic bands from 22 individual plants of V. vinifera L, indicating that grapevine EST datasets are a valuable source for the development of functional simple sequence repeat (SSR) markers. PMID- 22318548 TI - Role of fibrogenic markers in chronic hepatitis C and associated hepatocellular carcinoma. AB - Detection and follow up of fibrogenesis in chronic hepatitis C (CHC) is mandatory for early treatment and risk stratification. The current study included 120 patients with CHC, of whom 30 had liver cirrhosis (LC) and 30 had hepatocellular carcinoma (HCC). 15 wedge liver biopsies, taken during laparoscopic cholecystectomy, were included as normal controls. Cases were subjected to laboratory investigations, serologic markers for viral hepatitis and assessment of circulating levels of hyaluronic acid (HA) and platelet-derived growth factor (PDGF). Immunohistochemical expression of connective tissue growth factor (CTGF), PDGF and transforming growth factor-beta1 (TGF-beta1) was also carried out. A significant increase (p < 0.01) in serum HA was noticed in CHC, LC and HCC compared to controls. Although, a significant decrease in serum PDGF was detected in CHC and LC compared to controls, HCC values were comparable. A significant up regulation of CTGF was detected in CHC, LC and HCC (p < 0.01) in contrast to its limited mild expression in normal livers. Intense PDGF positive staining was noticed in CHC, LC and HCC compared to scattered faint expression in controls. The significant expression and marked intensity of PDGF staining matched the progress to tumorigenesis. A positive TGF-beta1 immunostaining was also noticed in CHC, LC and HCC. An intense and extensive cytoplasmic expression of TGF-beta1 was encountered in patients with LC revealing that CTGF, PDGF and TGF-beta1 act synergistically in LC. Data revealed that HA and CTGF may be implicated as important diagnostic parameters for assessment of hepatic fibrosis and PDGF for monitoring malignant transformation in CHC. PMID- 22318549 TI - Molecular cloning and expression analysis of IFN-beta promoter stimulator 1 in Tibetan pigs. AB - IFN-beta promoter stimulator 1 (IPS-1) is an important adaptor protein linking RIG-I/MDA5 to the downstream signaling molecules and plays the pivotal role in type I interferons induction. In this study, we cloned and characterized Tibetan porcine IPS-1, investigated the tissue distribution, compared different messenger RNA expression for IPS-1 between Tibetan and Crossbred (Duroc * Yorkshire * Landrace) pigs (DLY). The Tibetan porcine IPS-1 gene was first cloned from spleen. The entire open reading frame (ORF) of the IPS-1 is 1,575 bp and encodes for 524 amino acid residues, has 1 putative transmembrane domains, with a higher degree of sequence similarity with common pig (99.37%) and cattle (81.23%) than with human (70.20%) or mouse (63.44%). Real-time quantitative PCR analysis indicated that Tibetan porcine IPS-1 mRNA was most abundant in the liver and kidney. The expression of IPS-1 of Tibetan pigs in most tissues was higher than DLY pigs. PMID- 22318550 TI - Gene expression and pathologic response to neoadjuvant chemotherapy in breast cancer. AB - Pathologic complete response after neoadjuvant systemic treatment appears to be a valid surrogate for better overall survival in breast cancer patients. Currently, together with standard clinicopathologic assessment, novel molecular biomarkers are being exhaustively tested in order to look into the heterogeneity of breast cancer. The aim of our study was to examine an association between 23-gene real time-PCR expression assay including ABCB1, ABCC1, BAX, BBC3, BCL2, CASP3, CYP2D6, ERCC1, FOXC1, GAPDH, IGF1R, IRF1, MAP2, MAPK 8, MAPK9, MKI67, MMP9, NCOA3, PARP1, PIK3CA, TGFB3, TOP2A, and YWHAZ receptor status of breast cancer core biopsies sampled before neoadjuvant chemotherapy (anthracycline and taxanes) and pathologic response. Core-needle biopsies were collected from 42 female patients with inoperable locally advanced breast cancer or resectable tumors suitable for downstaging, before any treatment. Expressions of 23 genes were determined by means of TagMan low density arrays. Analysis of variance was used to select genes with discriminatory potential between receptor subtypes. We introduced a correction for false discovery rates (presented as q values) due to multiple hypothesis testing. Statistical analysis showed that seven genes out of a 23-gene real-time-PCR expression assay differed significantly in relation to pathologic response regardless of breast cancer subtypes. Among these genes, we identified: BAX (p = 0.0146), CYP2D6 (p = 0.0063), ERCC1 (p = 0.0231), FOXC1 (p = 0.0048), IRF1 (p = 0.0022), MAP2 (p = 0.0011), and MKI67 (p = 0.0332). The assessment of core biopsy gene profiles and receptor-based subtypes, before neoadjuvant therapy seems to predict response or resistance and to define new signaling pathways to provide more powerful classifiers in breast cancer, hence the need for further research. PMID- 22318551 TI - Isolation and characterization of two hydroperoxide lyase genes from grape berries : HPL isogenes in Vitis vinifera grapes. AB - C6 compounds are the major fraction of the volatile profiles of grape berries, contributing the typical 'green' aroma to the grape and wine. Hydroperoxide lyase (HPL) catalyzes the cleavage of fatty acid hydroperoxides to produce C6 compounds. Two hypothetical genes, VvHPL1 and VvHPL2 were cloned from grape berries (Vitis vinifera L. Cabernet Sauvignon). Bioinformatics analysis revealed that the proteins encoded by these two genes both belong to subfamily of cytochrome P450 and contain typical conserved domains of HPLs, and have high identity with HPLs from other plants. Prokaryotically-expressed VvHPL1 and VvHPL2 with thioredoxin-6xHis-fusion partner were confirmed to have enzymatic activity. VvHPL1 is specific for 13-HPOD (T) producing C6 aldehydes with relatively higher activity and VvHPL2 catalyzes the cleavage of both 9- and 13-hydroperoxides producing C6 aldehydes and C9 aldehydes respectively. Analysis of real time-PCR showed that VvHPL2 was highly expressed in the leaves and the flowers of the grapes, while relatively low transcript abundance was detected in the berries, tendril and stems; VvHPL1 had high expression in all detected tissues. During grape berry development, the expression of these two isogenes presented similar trends with a rapid increase after veraison and a decrease at full-ripen stage, which roughly corresponded to the accumulation of their volatile products. These data lay an essential foundation for further study on the accumulation and control of C6 volatiles in grape berries. PMID- 22318552 TI - Biochemical evaluation of a synthesized isoflavone-selenium complex by molecular spectra. AB - A coordination compound of 5, 7-dihydrox-4'-methoxyisoflavone and selenium was synthesized and its structure was identified by IR, LC-MS and (1)H-NMR. Its biochemical effects were investigated using bovine serum albumin (BSA) as a target protein molecule, in which process three-dimensional (3D) fluorescence spectra, ultraviolet spectra, circular dichroism (CD) spectra and fluorescence probe techniques were employed. The interaction of SEIF and BSA was discussed by fluorescence quenching method and Forster non-radiation energy transfer theory. The thermodynamic parameters DeltaH (theta), DeltaG (theta), DeltaS (theta) at different temperatures were calculated according to Van't Hoff isobaric equation and the results indicated the interaction was an exothermic as well as a spontaneous process. The binding site was explored by fluorescence probe method using warfarin and ibuprofen as markers. Intramolecular forces which are responsible for maintaining the binding were mainly hydrogen bond and van der Waals power. The average distance from the tryptophan residue in domain II of BSA (donor) to SEIF (acceptor) is 3.57 nm at body temperature. The conformation changes of BSA were investigated by 3D fluorescence and CD spectra. PMID- 22318553 TI - Adjustable structure transition and improved gases (H2, CO2) adsorption property of metal-organic framework MIL-53 by encapsulation of BNHx. AB - The structure transition of flexible MOF (MIL-53) can be adjusted by confinement of BNH(x) into MIL-53 channels. Hydrogen and carbon dioxide adsorption properties are also improved by incorporating BNH(x). At 77 K and 1 atm pressure hydrogen storage capacity can reach 2.0 wt% and CO(2) adsorption capacity is 4.5 mmol g( 1) at 273 K 1 atm. PMID- 22318554 TI - Case report: central venous catheterization via internal jugular vein with associated formation of perioperative venous thrombosis during surgery in the prone position. AB - An unusual case of central venous catheter (CVC)-related thrombosis during supine surgery in the prone position is presented. A 76-year-old woman was scheduled for elective surgery to repair a broken lumbar instrument. A single-lumen CVC was inserted via the right internal jugular vein. Surgery was performed in the prone position, with the patient's face directed downward in the standard median position (i.e., no rotation), but with slight forward flexion at the neck. After the surgery, the external jugular vein was dilated, and a postoperative X-ray revealed an infiltrative shadow in the right thoracic cavity. Because cervical echography showed dilated cervical veins with a "moyamoya-type" echo, possibly indicating a thrombus, contrast-enhanced computed tomography was performed, revealing a venous thrombus in the right internal jugular vein. An internal jugular venous-velocity measurement suggested that her slightly flexed neck position and her prone position during surgery may have kinked the internal jugular vein, causing engorgement with venous blood. The presence of the internal jugular venous catheter may have created thrombogenic conditions. A patient's position during surgery can reduce deep venous-flow velocity, and venous blood may stagnate, contributing greatly to thrombogenicity. We should consider a patient's position during surgery as a risk factor for thrombus formation, and a careful preoperative evaluation should be made as to which route should be chosen for CVC. PMID- 22318555 TI - Variation of activity demands in small-sided soccer games. AB - The aim of the present study was to examine the physical and technical activity during different periods within small-sided soccer games (SSGs). 20 elite players completed 3 different SSGs (2-a-side, 3-a-side and 4-a-side games) in which the number of ball touches per individual possession was fixed at a maximum of 2. The duration and the pitch size of each SSG were strictly controlled (2 min, 3 min, 4 min, respectively; 1:75 m2) with each period repeated 4 times (P1, P2, P3, P4). The physical and technical activities, heart rate responses, blood lactate concentration and rating of perceived exertion (RPE) were analysed. The results showed a decrease of high and very high-intensity activities (from - 26.2% to - 37.7%, P<0.001), an increase of blood lactate concentration (from + 28.0% to + 76.9%), RPE (from + 29.0% to + 32.8%), and heart rate responses (~ 6.6%), and a significant alteration of technical activities from P1 to P4 in each SSG. The greatest differences from P1 and P4 were observed for the 2-a-side game when compared to the 3-a-side and 4-a-side games (P<0.05) for each variable analysed . In conclusion, the variation of the player's activity throughout the periods indicates that the duration and number of exercise periods used within SSGs is an important variable in determining the training stimulus in soccer-specific training. PMID- 22318556 TI - Comparison of estimated anterior cruciate ligament tension during a typical and flexed knee and hip drop landing using sagittal plane knee modeling. AB - Noncontact mechanisms, such as landing from a jump, account for over 70% of all anterior cruciate ligament injuries. Increased knee and hip flexion during landing has been suggested to decrease anterior cruciate ligament tension; however, current literature utilizing knee modeling approaches has not investigated this. Our purpose was to compare estimated anterior cruciate ligament tension in females between a typical and flexed knee and hip drop landing performance. A sagittal plane knee model based on kinematic, kinetic, electromyography, and cadaveric data was used to estimate forces on the anterior cruciate ligament during a typical and flexed drop landing for 23 females. Model estimated peak anterior cruciate ligament tension decreased by 10% during the flexed landing performance (p=0.008). This was accounted for by an increase in hamstring shear force by 6% of body weight and a reduction in patellar tendon shear force and femur-tibia shear force by 3% of body weight each. Results suggest that simple verbal cues for increased knee and hip flexion during landing may be effective in reducing anterior cruciate ligament tension and potential risk of injury during landing. PMID- 22318557 TI - Intracycle velocity variation of the body centre of mass in front crawl. AB - Our aim was to determine the 3-dimensional intracycle velocity variation (IVV) of the body centre of mass during a 200-m front crawl event, and to analyse its relation with the segmental hand kinematics and the velocity (v) changes. 10 high level male swimmers performed a 200-m front crawl swim at maximal intensity. 2 above- and 4 underwater cameras were used to record one complete non-breathing cycle for each 50-m lap, and APASystem was used for imaging processing. The coefficient of variation was calculated to assess the IVV in the horizontal (x), vertical (y), and lateral (z) axes; hand kinematics was also computed. IVV remained stable across the 200 m, and significant correlations were found between vx and vmaxx (r=0.55), vminx (r = 0.68), IVVx (r = -0.45), and IVVz (r = -0.45) (all p<=0.01). In addition, IVVx was correlated with the backward horizontal amplitude normalized to stroke length (r = 0.54), IVVy with hand angular velocity (r = -0.40), and IVVz with the elbow angle range in the pull phase (r = - 0.37) (all p<0.05). This study shows the stability of the IVV (x,y,z), the inverse relation of the IVV (x, z) with v, the direct relation of the vmaxx and vminx with v, and the influence of the hand kinematics in the IVV. PMID- 22318558 TI - Growth hormone does not stimulate early healing in rat tendons. AB - Growth Hormone stimulates bone growth and fracture repair. It acts mainly by increasing the systemic levels of IGF-1. Local treatment with IGF-1 appears to stimulate tendon healing. We therefore hypothesized that systemic treatment with Growth Hormone would also stimulate tendon healing. Rat Achilles tendons were transected and left to heal. 4 groups were studied. Intramuscular injections of botulinum toxin A (Botox) were used to reduce loading in 2 groups. The animals were randomized to twice daily injections of Growth Hormone (n=2*10) or saline (n=2*10), and killed after 10 days. Healing was assessed by mechanical testing. Muscle paralysis induced by Botox reduced the strength of the healing tendon by two thirds. Growth Hormone increased femoral and tibial length in the unloaded, and femoral and tibial weight in the loaded group. Body weight and muscle weight were increased in both. In contrast, there was no increase in the strength of the healing tendons, regardless of mechanical loading status. An increase in peak force of the loaded healing tendons by more than 5% could be excluded with 95% confidence. In spite of its stimulatory effects on other tissues, Growth Hormone did not appear to stimulate tendon or tendon repair. PMID- 22318559 TI - Effect of different pushing speeds on bench press. AB - The purpose of this study was to investigate the effect on muscular strength after a 3-week training with the bench-press at a fixed pushing of 80-100% maximal speed (FPS) and self-selected pushing speed (SPS). 20 resistance-trained subjects were divided at random in 2 groups differing only regarding the pushing speed: in the FPS group (n=10) it was equal to 80-100% of the maximal speed while in the SPS group (n=10) the pushing speed was self-selected. Both groups were trained twice a week for 3 weeks with a load equal to 85% of 1RM and monitored with the encoder. Before and after the training we measured pushing speed and maximum load. Significant differences between and within the 2 groups were pointed out using a 2-way ANOVA for repeated measures. After 3 weeks a significant improvement was shown especially in the FPS group: the maximum load improved by 10.20% and the maximal speed by 2.22%, while in the SPS group the effect was <1%. This study shows that a high velocity training is required to increase the muscle strength further in subjects with a long training experience and this is possible by measuring the individual performance speed for each load. PMID- 22318560 TI - Acute effects of distribution of rest between repetitions. AB - The purpose of this study was to compare acute mechanical and metabolic effects of 2 sessions of resistance training equated by volume and total resting time but with different set configuration: sets to failure (FS) vs. distribution of rest between each repetition (NFS). 10 male judoists completed a session consisting of 3 sets to failure of parallel back squat with 4 repetitions at maximum load, and a rest of 3 min between the sets. At least 72 h later subjects developed the same volume, but total resting time was distributed among individual repetitions. Before and after sessions isometric force and mean propulsive velocity with load corresponding to maximum propulsive power were assessed. Results showed that in respect to FS, NFS showed an 18.94% (+/- 17.98) higher average mean propulsive velocity during session (0.42 +/- 0.04 vs. 0.35 +/- 0.08 m.s - 1; p=0.009), lower blood lactate concentration after session (maximum average value 1.52 +/- 0.77 vs. 3.95 +/- 1.82; session effect: p=0.001) and higher mean propulsive velocity with load corresponding to maximum propulsive power (mean propulsive velocity immediately after session 0.64 +/- 0.09 vs. 0.59 +/- 0.12 m.s - 1; session effect: p=0.019). These data show that distribution of rest in sessions equated for volume and total resting time determines differences in performance during sessions and mechanical or metabolic acute effects. PMID- 22318561 TI - Detraining decreases Hb(mass) of triathletes. AB - Haemoglobin mass (Hbmass) determination using CO rebreathing may assist to detect illegal blood doping practices, however variations in Hbmass with periods of intensive training and detraining must be quantified. This study aimed to determine the effect of a 30-day period of detraining on Hbmass in ultra endurance triathletes. 9 male recreational triathletes (29-44 years) participated in the study. Hbmass was assessed using CO rebreathing 30 days and 10 days before an ultra-endurance triathlon and after ~10, 20 and 30 days of detraining following the race. VO2max was assessed 10 days before the race and also after the 30-day detraining period, which consisted of an 87% reduction in training hours. After 30-days of detraining there was a 3.1% decrease in mean Hbmass from 868+/-99 to 840+/-94 g, (p=0.03), and a 4.7% decrease in mean VO2max from 4.83+/ 0.29 to 4.61+/-0.41 L/min as well as a 2.8% increase of body mass from 75.1+/-6.4 to 77.1+/-6.1 kg and a 28% increase in skinfold total from 43.9+/-14.2 to 55.1+/ 14.0 mm. Individual decreases in Hbmass following detraining would need to be considered if using Hbmass for anti-doping purposes. PMID- 22318562 TI - No effect of intravenous Actovegin(r) on peak aerobic capacity. AB - There is much speculation that Actovegin(r) is ergogenic, but no scientific work has been published in this field. 8 participants [mean(+/- SD) age, height and mass of 24 (7) years, 1.76 (0.07) m and 80.1 (9.1) kg, respectively] completed 3 exhaustive arm crank ergometry tests. Following Baseline testing 2 further tests were performed 2 h following the injection of either 40 ml of Actovegin(r) or a saline Placebo. Peak power (Wpeak), peak physiological responses, concentrations of blood glucose and lactate, exercise efficiency (%), VO2 gain (ml.W-1), and the respiratory compensation point (RCP) were determined. Repeated measures ANOVA tests were used to analyse data with significance accepted at p<=0.05. Values of mean (+/-90% CI) bias were calculated to further explore quantitative differences between trials. Strong trends for variations in Wpeak (p=0.054) and RCP (p=0.054) were evident; likely meaningful effects existed between the Baseline and both injection trials, but only a trivial effect was noted between Placebo and Actovegin(r) (bias: Wpeak 0.8+/-3.2 and RCP; 2.5+/-4.7 W). Concentrations of blood lactate and glucose changed across time, but did not differ between the 3 trials. Our data suggests the Actovegin(r) is not ergogenic and did not influence functional capacity in the context of the exhaustive, upper-body test employed. PMID- 22318563 TI - Predictability of anthrax infection in the Serengeti, Tanzania. AB - Anthrax is endemic throughout Africa, causing considerable livestock and wildlife losses and severe, sometimes fatal, infection in humans. Predicting the risk of infection is therefore important for public health, wildlife conservation and livestock economies. However, because of the intermittent and variable nature of anthrax outbreaks, associated environmental and climatic conditions, and diversity of species affected, the ecology of this multihost pathogen is poorly understood.We explored records of anthrax from the Serengeti ecosystem in north west Tanzania where the disease has been documented in humans, domestic animals and a range of wildlife. Using spatial and temporal case-detection and seroprevalence data from wild and domestic animals, we investigated spatial, environmental, climatic and species-specific associations in exposure and disease.Anthrax was detected annually in numerous species, but large outbreaks were spatially localized, mostly affecting a few focal herbivores.Soil alkalinity and cumulative weather extremes were identified as useful spatial and temporal predictors of exposure and infection risk, and for triggering the onset of large outbreaks.Interacting ecological and behavioural factors, specifically functional groups and spatiotemporal overlap, helped to explain the variable patterns of infection and exposure among species.Synthesis and applications. Our results shed light on ecological drivers of anthrax infection and suggest that soil alkalinity and prolonged droughts or rains are useful predictors of disease occurrence that could guide risk-based surveillance. These insights should inform strategies for managing anthrax including prophylactic livestock vaccination, timing of public health warnings and antibiotic provision in high-risk areas. However, this research highlights the need for greater surveillance (environmental, serological and case-detection-orientated) to determine the mechanisms underlying anthrax dynamics. PMID- 22318564 TI - Facing up to flu. PMID- 22318565 TI - Gas and air. PMID- 22318566 TI - Hypocritical oaths. PMID- 22318567 TI - Finding the true value of US climate science. PMID- 22318579 TI - Air sampling reveals high emissions from gas field. PMID- 22318580 TI - Fission power back on NASA's agenda. PMID- 22318581 TI - Lab flu may not aid vaccines. PMID- 22318582 TI - Japan finds a key to unlock philanthropy. PMID- 22318583 TI - Drug bests cystic-fibrosis mutation. PMID- 22318584 TI - Duplicate-grant case puts funders under pressure. PMID- 22318585 TI - Human experiments: First, do harm. PMID- 22318590 TI - Public health: Use snail ecology to assess dam impact. PMID- 22318591 TI - Policy-making: Scientists cannot compete as lobbyists. PMID- 22318592 TI - Whaling: Quota trading won't work. PMID- 22318593 TI - Marine management: Expand Australia's sustainable fisheries. PMID- 22318594 TI - Asian medicine: A way to compare data. PMID- 22318595 TI - Thermodynamics: The fridge gate. PMID- 22318596 TI - Genetics: How intelligence changes with age. PMID- 22318597 TI - Extrasolar planets: An Earth-sized duo. PMID- 22318598 TI - Infectious disease: Genomics decodes drug action. PMID- 22318599 TI - Quantum optics: Controlling the light. PMID- 22318600 TI - Cell biology: Destruction deconstructed. PMID- 22318602 TI - A tidally distorted dwarf galaxy near NGC 4449. AB - NGC 4449 is a nearby Magellanic irregular starburst galaxy with a B-band absolute magnitude of -18 and a prominent, massive, intermediate-age nucleus at a distance from Earth of 3.8 megaparsecs (ref. 3). It is wreathed in an extraordinary neutral hydrogen (H I) complex, which includes rings, shells and a counter rotating core, spanning ~90 kiloparsecs (kpc; refs 1, 4). NGC 4449 is relatively isolated, although an interaction with its nearest known companion--the galaxy DDO 125, some 40 kpc to the south--has been proposed as being responsible for the complexity of its H I structure. Here we report the presence of a dwarf galaxy companion to NGC 4449, namely NGC 4449B. This companion has a V-band absolute magnitude of -13.4 and a half-light radius of 2.7 kpc, with a full extent of around 8 kpc. It is in a transient stage of tidal disruption, similar to that of the Sagittarius dwarf near the Milky Way. NGC 4449B exhibits a striking S-shaped morphology that has been predicted for disrupting galaxies but has hitherto been seen only in a dissolving globular cluster. We also detect an additional arc or disk ripple embedded in a two-component stellar halo, including a component extending twice as far as previously known, to about 20 kpc from the galaxy's centre. PMID- 22318601 TI - The Drosophila melanogaster Genetic Reference Panel. AB - A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics. PMID- 22318603 TI - Electromagnetically induced transparency with resonant nuclei in a cavity. AB - The manipulation of light-matter interactions by quantum control of atomic levels has had a profound impact on optical sciences. Such manipulation has many applications, including nonlinear optics at the few-photon level, slow light, lasing without inversion and optical quantum information processing. The critical underlying technique is electromagnetically induced transparency, in which quantum interference between transitions in multilevel atoms renders an opaque medium transparent near an atomic resonance. With the advent of high-brilliance, accelerator-driven light sources such as storage rings or X-ray lasers, it has become attractive to extend the techniques of optical quantum control to the X ray regime. Here we demonstrate electromagnetically induced transparency in the regime of hard X-rays, using the 14.4-kiloelectronvolt nuclear resonance of the Mossbauer isotope iron-57 (a two-level system). We exploit cooperative emission from ensembles of the nuclei, which are embedded in a low-finesse cavity and excited by synchrotron radiation. The spatial modulation of the photonic density of states in a cavity mode leads to the coexistence of superradiant and subradiant states of nuclei, respectively located at an antinode and a node of the cavity field. This scheme causes the nuclei to behave as effective three level systems, with two degenerate levels in the excited state (one of which can be considered metastable). The radiative coupling of the nuclear ensembles by the cavity field establishes the atomic coherence necessary for the cancellation of resonant absorption. Because this technique does not require atomic systems with a metastable level, electromagnetically induced transparency and its applications can be transferred to the regime of nuclear resonances, establishing the field of nuclear quantum optics. PMID- 22318604 TI - Thresholdless nanoscale coaxial lasers. AB - The effects of cavity quantum electrodynamics (QED), caused by the interaction of matter and the electromagnetic field in subwavelength resonant structures, have been the subject of intense research in recent years. The generation of coherent radiation by subwavelength resonant structures has attracted considerable interest, not only as a means of exploring the QED effects that emerge at small volume, but also for its potential in applications ranging from on-chip optical communication to ultrahigh-resolution and high-throughput imaging, sensing and spectroscopy. One such strand of research is aimed at developing the 'ultimate' nanolaser: a scalable, low-threshold, efficient source of radiation that operates at room temperature and occupies a small volume on a chip. Different resonators have been proposed for the realization of such a nanolaser--microdisk and photonic bandgap resonators, and, more recently, metallic, metallo-dielectric and plasmonic resonators. But progress towards realizing the ultimate nanolaser has been hindered by the lack of a systematic approach to scaling down the size of the laser cavity without significantly increasing the threshold power required for lasing. Here we describe a family of coaxial nanostructured cavities that potentially solve the resonator scalability challenge by means of their geometry and metal composition. Using these coaxial nanocavities, we demonstrate the smallest room-temperature, continuous-wave telecommunications-frequency laser to date. In addition, by further modifying the design of these coaxial nanocavities, we achieve thresholdless lasing with a broadband gain medium. In addition to enabling laser applications, these nanoscale resonators should provide a powerful platform for the development of other QED devices and metamaterials in which atom field interactions generate new functionalities. PMID- 22318605 TI - Supercontinent cycles and the calculation of absolute palaeolongitude in deep time. AB - Traditional models of the supercontinent cycle predict that the next supercontinent--'Amasia'--will form either where Pangaea rifted (the 'introversion' model) or on the opposite side of the world (the 'extroversion' models). Here, by contrast, we develop an 'orthoversion' model whereby a succeeding supercontinent forms 90 degrees away, within the great circle of subduction encircling its relict predecessor. A supercontinent aggregates over a mantle downwelling but then influences global-scale mantle convection to create an upwelling under the landmass. We calculate the minimum moment of inertia about which oscillatory true polar wander occurs owing to the prolate shape of the non hydrostatic Earth. By fitting great circles to each supercontinent's true polar wander legacy, we determine that the arc distances between successive supercontinent centres (the axes of the respective minimum moments of inertia) are 88 degrees for Nuna to Rodinia and 87 degrees for Rodinia to Pangaea--as predicted by the orthoversion model. Supercontinent centres can be located back into Precambrian time, providing fixed points for the calculation of absolute palaeolongitude over billion-year timescales. Palaeogeographic reconstructions additionally constrained in palaeolongitude will provide increasingly accurate estimates of ancient plate motions and palaeobiogeographic affinities. PMID- 22318607 TI - Functional genomics: The changes that count. PMID- 22318606 TI - Functional dissection of lysine deacetylases reveals that HDAC1 and p300 regulate AMPK. AB - First identified as histone-modifying proteins, lysine acetyltransferases (KATs) and deacetylases (KDACs) antagonize each other through modification of the side chains of lysine residues in histone proteins. Acetylation of many non-histone proteins involved in chromatin, metabolism or cytoskeleton regulation were further identified in eukaryotic organisms, but the corresponding enzymes and substrate-specific functions of the modifications are unclear. Moreover, mechanisms underlying functional specificity of individual KDACs remain enigmatic, and the substrate spectra of each KDAC lack comprehensive definition. Here we dissect the functional specificity of 12 critical human KDACs using a genome-wide synthetic lethality screen in cultured human cells. The genetic interaction profiles revealed enzyme-substrate relationships between individual KDACs and many important substrates governing a wide array of biological processes including metabolism, development and cell cycle progression. We further confirmed that acetylation and deacetylation of the catalytic subunit of the adenosine monophosphate-activated protein kinase (AMPK), a critical cellular energy-sensing protein kinase complex, is controlled by the opposing catalytic activities of HDAC1 and p300. Deacetylation of AMPK enhances physical interaction with the upstream kinase LKB1, leading to AMPK phosphorylation and activation, and resulting in lipid breakdown in human liver cells. These findings provide new insights into previously underappreciated metabolic regulatory roles of HDAC1 in coordinating nutrient availability and cellular responses upstream of AMPK, and demonstrate the importance of high-throughput genetic interaction profiling to elucidate functional specificity and critical substrates of individual human KDACs potentially valuable for therapeutic applications. PMID- 22318609 TI - beta-arrestin-1 participates in thrombosis and regulates integrin aIIbbeta3 signalling without affecting P2Y receptors desensitisation and function. AB - beta-arrestin-1 (beta-arr1) and beta-arrestin-2 (beta-arr2) are cytosolic proteins well-known to participate in G protein-coupled receptor desensitisation and signalling. We used genetically-inactivated mice to evaluate the role of beta arr1 or beta-arr2 in platelet function, P2Y receptor desensitisation, haemostasis and thrombosis. Platelet aggregation, soluble fibrinogen binding and P-selectin exposure induced by various agonists were near normal in beta-arr1-/- and beta arr2-/- platelets. In addition, deficiency in beta-arr1 or beta-arr2 was not critical for P2Y receptors desensitisation. A functional redundancy between beta arr1 and beta-arr2 may explain these unchanged platelet responses. Interestingly, beta-arr1-/- but not beta-arr2-/- mice were protected against laser- and FeCl3 induced thrombosis. The tail bleeding times, number of rebleeds and volume of blood loss were unchanged in beta-arr1-/- and beta-arr2-/- mice, suggesting no defect in haemostasis. beta-arr1-/- platelet activation upon adhesion to immobilised fibrinogen was inhibited, as attested by a 37 +/- 5% (n = 3, p<0.0001) decrease in filopodia extension, suggesting defective signalling through integrin alphaIIbbeta3. beta-arr1 appeared to be located downstream of Src family kinases and to regulate alphaIIbbeta3 signalling by increasing Akt phosphorylation. Overall, this study supports a role for beta-arr1 in promoting thrombus formation, in part through its participation in alphaIIbbeta3 signalling, and no role of beta-arr1 and beta-arr2 in agonist-induced platelet activation and P2Y receptors desensitisation. PMID- 22318610 TI - Is EPCR a multi-ligand receptor? Pros and cons. AB - In the last decade, the endothelial cell protein C/activated protein C receptor (EPCR) has received considerable attention. The role initially attributed to EPCR, i.e. the enhancement of protein C (PC) activation by the thrombin thrombomodulin complex on the surface of the large vessels, although important, did not go beyond the haemostasis scenario. However, the discovery of the cytoprotective, anti-inflammatory and anti-apoptotic features of the activated PC (APC) and the required involvement of EPCR for APC to exert such actions did place the receptor in a privileged position in the crosstalk between coagulation and inflammation. The last five years have shown that PC/APC are not the only molecules able to interact with EPCR. Factor VII/VIIa (FVII/VIIa) and factor Xa (FXa), two other serine proteases that play a central role in haemostasis and are also involved in signalling processes influencing wound healing, tissue remodelling, inflammation or metastasis, have been reported to bind to EPCR. These observations have paved the way for an exploration of unsuspected new roles for the receptor. This review aims to offer a new image of EPCR in the light of its extended panel of ligands. A brief update of what is known about the APC evoked EPCR-dependent cell signalling mechanisms is provided, but special care has been taken to assemble all the information available about the interaction of EPCR with FVII/VIIa and FXa. PMID- 22318611 TI - In situ TEM observation of lithium nanoparticle growth and morphological cycling. AB - Lithium fluoride crystals were subjected to electron beam irradiation at 200 and 300 keV using transmission electron microscopy in order to study in situ fabrication of Li nanostructures. We observed that LiF crystals decompose in a unique way different to all other metal halides: Fluorine ablation and salt-to metal conversion is non-local and due to a rapid lateral diffusion of Li, the life cycle from nucleation to annihilation of fresh Li nano-crystals can be observed at a distance from the Li-source, the irradiated salt. Growth, shape transition and annihilation of Li nanostructures follow at slow enough speed for live video recording with resolution of 25 frames per second. The equilibrium shapes of pure Li nano-crystals range from cubic to rod-shaped and ball-shaped and up to 300 nm size. By varying the e-beam flux of irradiation, transitions from cube to spherical shape can be induced cyclically. PMID- 22318613 TI - 'Materiality, Belief, Ritual - Archaeology and Material Religion'. An Introduction. PMID- 22318612 TI - Prostate cancer pain management: EAU guidelines on pain management. AB - CONTEXT: The first publication of the European Association of Urology (EAU) guidelines on Pain Management in Urology dates back to 2003. Since then, these guidelines have been revised several times with the most recent update achieved in 2010. OBJECTIVE: Given the scope of the full text guidelines, condensing the entire document was no option in this context. This paper presents a summary of the section of pain management in prostate cancer, a topic considered of direct relevance for the practicing urologist. EVIDENCE ACQUISITION: A multidisciplinary expert panel (urologists, anaesthesiologists, radio-oncologists) compiled this document based on a comprehensive consultation of the literature. Data were identified through a structured search, covering the time frame 2000 through 2010, using Medline and Embase as well as the Cochrane Library of systematic reviews. The scientific papers were weighed by the expert panel and a level of evidence (LE) assigned. Recommendations have been graded as a means to provide transparency between the underlying evidence and the guidance provided. Pain can occur in each stage of prostate cancer. It could be caused by the cancer itself (77%), be related to the cancer treatment (19%) or be unrelated to either (3%). The incidence of pain rises to 90% as patients enter the terminal phase of their illness. The physician's task is to discover and treat the cause of pain and the pain itself, to determine whether or not the underlying cause is treatable, to provide pain relief and palliative care. These tasks more often than not require a multidisciplinary team. Pain management involves mainly pharmacotherapy, including direct anticancer therapy such as androgen deprivation and chemotherapy, as well as analgetics, for instance non-steroidal anti-inflammatory drugs (NSAIDs) or opioids. In case of local impairment due to the cancer or its metastases, primary treatments like surgery, radiotherapy or radionuclides can provide adequate pain relief. In addition, in palliative care, functional, psychosocial and spiritual support are essential components. The EAU guidelines on Pain Management in Urology are available in a number of different formats through the EAU Central Office and the EAU website ( http://www.uroweb.org/guidelines/online-guidelines/ ). CONCLUSION: The mainstay of pain management in prostate cancer is involvement of and collaboration between experts from a number of disciplines to be able to achieve a complete pain evaluation and to offer the full range of treatment options. Prostate cancer related pain can, in most cases, be managed effectively, but it requires careful monitoring where a balance should be found between pain relief and potential side effects of treatment and quality of life (QoL). PMID- 22318614 TI - Impediments to clinical research in the United States. AB - Clinical trials are essential to the evaluation of promising scientific discoveries, but they are becoming unsustainably burdensome, threatening to deprive patients and health-care providers of new therapies and new evidence to guide the use of existing treatments. Regulations are often blamed for impeding clinical research, but there are other elements of the clinical trials enterprise that also have the potential to add burdens, through either imposed requirements or incentives that do not favor clinical research (Figure 1). PMID- 22318615 TI - The prevention and treatment of missing data in clinical trials: an FDA perspective on the importance of dealing with it. AB - At the request of the Food and Drug Administration (FDA) and with its funding, the Panel on the Handling of Missing Data in Clinical Trials was created by the National Research Council's Committee on National Statistics. This panel recently published a report(1) with recommendations that will be of use not only to the FDA but also to the entire clinical trial community so that the latter can take measures to improve the conduct and analysis of clinical trials. PMID- 22318616 TI - The role of physiologically based pharmacokinetic modeling in regulatory review. AB - During regulatory review of clinical pharmacology data in new drug applications and biologics license applications, questions are routinely asked about how intrinsic factors (e.g., organ dysfunction, age, and genetics) and extrinsic factors (e.g., drug-drug interactions) might influence dose-response and exposure response and about the impact of these individual factors on the efficacy and safety of the candidate compound. Physiologically based pharmacokinetic (PBPK) modeling and simulation is one of the tools that can be used to address these critical questions. PMID- 22318617 TI - The state of the art in the development of biosimilars. AB - The development of biologic therapeutics using advanced technology to copy and improve on nature's design of complex peptides, proteins, and glycoproteins has enabled the treatment of diseases in entirely new ways and brought unique and lifesaving treatments to many people. However, at least in part because of cost pressures, access to these truly amazing products has not been uniformly available; many patients do not qualify for these treatments, or the treatment is postponed until disabilities accumulate. The development of biosimilars- essentially copies of the original biologic drugs after patent expiration--allows for wider and, as important, earlier access to these agents because of their lower cost and consequently greater affordability. The development and commercialization of biosimilars can help address unmet medical needs by improving access to well-established therapeutic interventions while improving health-care affordability. PMID- 22318619 TI - The innovative medicines initiative: a European response to the innovation challenge. AB - The Innovative Medicines Initiative (IMI) was launched in 2008 as a large-scale public-private partnership between the European Commission and the European Federation of Pharmaceutical Industries and Associations (EFPIA). With a total budget of ?2 billion, the IMI aims to boost the development of new medicines across Europe by implementing new collaborative endeavors between large pharmaceutical companies and other key actors in the health-care ecosystem, i.e., academic institutions, small and medium enterprises, patients, and regulatory authorities. Projects conducted by IMI consortia have already delivered meaningful results, providing proof-of-concept evidence for the efficiency of this new model of collaboration. In this article we review recent achievements of the IMI consortia and discuss the growing interest in the IMI as a best-practice model to reinvigorate drug development. PMID- 22318618 TI - Induction of CYP2C19 and CYP3A activity following repeated administration of efavirenz in healthy volunteers. AB - Drug-drug interactions involving efavirenz are of major concern in clinical practice. We evaluated the effects of multiple doses of efavirenz on omeprazole 5 hydroxylation (CYP2C19) and sulfoxidation (CYP3A). Healthy volunteers (n = 57) were administered a single 20 mg oral dose of racemic omeprazole either with a single 600 mg oral dose of efavirenz or after 17 days of administration of 600 mg/day of efavirenz. The concentrations of racemic omeprazole, 5 hydroxyomeoprazole (and their enantiomers), and omeprazole sulfone in plasma were measured using a chiral liquid chromatography-tandem mass spectrometry method. Relative to single-dose treatment, multiple doses of efavirenz significantly decreased (P < 0.0001) the area under the plasma concentration-time curve from 0 to infinity (AUC(0-infinity)) of racemic-, R- and S-omeprazole (2.01- to 2.15 fold) and the corresponding AUC(0-infinity) metabolic ratio (MR) for 5 hydroxyomeprazole (1.36- to 1.44-fold) as well as the MR for omeprazole sulfone (~2.0) (P < 0.0001). The significant reduction in the AUC of 5-hydroxyomeprazole after repeated efavirenz dosing suggests induction of sequential metabolism and mixed inductive/inhibitory effects of efavirenz on CYP2C19. In conclusion, efavirenz enhances omeprazole metabolism in a nonstereoselective manner through induction of CYP3A and CYP2C19 activity. PMID- 22318620 TI - Effect of the market withdrawal of carisoprodol on use of other prescribed drugs with abuse potential. AB - Carisoprodol, a centrally acting muscle relaxant indicated for acute lower back pain, has been available in Europe and the United States since 1959. Studies indicating increased risk of abuse or addiction led to withdrawal of the drug from the market in Norway and other EU countries in 2008. In this nationwide longitudinal prescription study of 53,116 individuals in Norway, previous users of carisoprodol switched, to a limited extent, to other prescribed drugs with abuse potential after the withdrawal. PMID- 22318621 TI - APEC Harmonization Center: challenges and issues relating to multiregional clinical trials in the APEC region. AB - The Asia-Pacific Economic Cooperation (APEC) Harmonization Center (AHC) was established in 2009 with the purpose of promoting harmonization of regulatory processes for drugs and medical devices. The AHC held three training workshops on multiregional clinical trials (MRCTs); these workshops provided forums for discussing the value and potential benefits of MRCTs. Participants from regulatory agencies, the pharmaceutical industry, and academia identified many issues and made recommendations for resolving major challenges with the aim of improving the capacity of the Asia-Pacific region to carry out MRCTs. PMID- 22318622 TI - Germaindacenodithiophene based low band gap polymers for organic solar cells. AB - We report the first synthesis of a fused germaindacenodithiophene monomer and its polymerisation with 2,1,3-benzothiadiazole by Suzuki polycondensation. The resulting polymer, PGeTPTBT, is semicrystalline, despite the presence of four bulky 2-ethylhexyl groups. Blends with P(70)CBM afford solar cells with efficiencies of 5.02%. PMID- 22318623 TI - Axial (spinal) gout. AB - Gout is a common metabolic disorder resulting from supersaturation of uric acid in extracellular fluid and deposition of monosodium urate crystals in tissues. Gouty arthritis typically affects the peripheral joints of the appendicular skeleton, especially the feet and hands. Gouty involvement of the spine, however, is not as rare as generally perceived. Although it may be asymptomatic, tophaceous axial gout is also a well-documented cause of acute back pain, radiculopathy, and frank cord compression. As with the appendicular skeleton, it takes several years of gout before radiological evidence of erosive change or tophi is apparent in the axial skeleton. This is best detected by CT imaging. The sequelae of cord compression can be reversed with timely surgical intervention and maintenance of uric acid-lowering therapy. The long-term effects of urate lowering therapies on axial gout have not been studied. PMID- 22318625 TI - Retinoic acid signalling during development. AB - Retinoic acid (RA) is a vitamin A-derived, non-peptidic, small lipophilic molecule that acts as ligand for nuclear RA receptors (RARs), converting them from transcriptional repressors to activators. The distribution and levels of RA in embryonic tissues are tightly controlled by regulated synthesis through the action of specific retinol and retinaldehyde dehydrogenases and by degradation via specific cytochrome P450s (CYP26s). Recent studies indicate that RA action involves an interplay between diffusion (morphogen-like) gradients and the establishment of signalling boundaries due to RA metabolism, thereby allowing RA to finely control the differentiation and patterning of various stem/progenitor cell populations. Here, we provide an overview of the RA biosynthesis, degradation and signalling pathways and review the main functions of this molecule during embryogenesis. PMID- 22318624 TI - Human pre-implantation embryo development. AB - Understanding human pre-implantation development has important implications for assisted reproductive technology (ART) and for human embryonic stem cell (hESC) based therapies. Owing to limited resources, the cellular and molecular mechanisms governing this early stage of human development are poorly understood. Nonetheless, recent advances in non-invasive imaging techniques and molecular and genomic technologies have helped to increase our understanding of this fascinating stage of human development. Here, we summarize what is currently known about human pre-implantation embryo development and highlight how further studies of human pre-implantation embryos can be used to improve ART and to fully harness the potential of hESCs for therapeutic goals. PMID- 22318626 TI - Cis-regulatory properties of medaka synexpression groups. AB - During embryogenesis, tissue specification is triggered by the expression of a unique combination of developmental genes and their expression in time and space is crucial for successful development. Synexpression groups are batteries of spatiotemporally co-expressed genes that act in shared biological processes through their coordinated expression. Although several synexpression groups have been described in numerous vertebrate species, the regulatory mechanisms that orchestrate their common complex expression pattern remain to be elucidated. Here we performed a pilot screen on 560 genes of the vertebrate model system medaka (Oryzias latipes) to systematically identify synexpression groups and investigate their regulatory properties by searching for common regulatory cues. We find that synexpression groups share DNA motifs that are arranged in various combinations into cis-regulatory modules that drive co-expression. In contrast to previous assumptions that these genes are located randomly in the genome, we discovered that genes belonging to the same synexpression group frequently occur in synexpression clusters in the genome. This work presents a first repertoire of synexpression group common signatures, a resource that will contribute to deciphering developmental gene regulatory networks. PMID- 22318627 TI - Musculin and TCF21 coordinate the maintenance of myogenic regulatory factor expression levels during mouse craniofacial development. AB - The specification of the skeletal muscle lineage during craniofacial development is dependent on the activity of MYF5 and MYOD, two members of the myogenic regulatory factor family. In the absence of MYF5 or MYOD there is not an overt muscle phenotype, whereas in the double Myf5;MyoD knockout branchiomeric myogenic precursors fail to be specified and skeletal muscle is not formed. The transcriptional regulation of Myf5 is controlled by a multitude of regulatory elements acting at different times and anatomical locations, with at least five operating in the branchial arches. By contrast, only two enhancers have been implicated in the regulation of MyoD. In this work, we characterize an enhancer element that drives Myf5 expression in the branchial arches from 9.5 days post coitum and show that its activity in the context of the entire locus is dependent on two highly conserved E-boxes. These binding sites are required in a subset of Myf5-expressing cells including both progenitors and those which have entered the myogenic pathway. The correct levels of expression of Myf5 and MyoD result from activation by musculin and TCF21 through direct binding to specific enhancers. Consistent with this, we show that in the absence of musculin the timing of activation of Myf5 and MyoD is not affected but the expression levels are significantly reduced. Importantly, normal levels of Myf5 expression are restored at later stages, which might explain the absence of particular muscles in the Msc;Tcf21 double-knockout mice. PMID- 22318628 TI - Regulation of cochlear convergent extension by the vertebrate planar cell polarity pathway is dependent on p120-catenin. AB - The vertebrate planar cell polarity (PCP) pathway consists of conserved PCP and ciliary genes. During development, the PCP pathway regulates convergent extension (CE) and uniform orientation of sensory hair cells in the cochlea. It is not clear how these diverse morphogenetic processes are regulated by a common set of PCP genes. Here, we show that cellular contacts and geometry change drastically and that the dynamic expression of N-cadherin and E-cadherin demarcates sharp boundaries during cochlear extension. The conditional knockout of a component of the adherens junctions, p120-catenin, leads to the reduction of E-cadherin and N cadherin and to characteristic cochlear CE defects but not misorientation of hair cells. The specific CE defects in p120-catenin mutants are in contrast to associated CE and hair cell misorientation defects observed in common PCP gene mutants. Moreover, the loss-of-function of a conserved PCP gene, Vangl2, alters the dynamic distribution of N-cadherin and E-cadherin in the cochlea and causes similar abnormalities in cellular morphology to those found in p120-catenin mutants. Conversely, we found that Pcdh15 interacts genetically with PCP genes to regulate the formation of polar hair bundles, but not CE defects in the cochlea. Together, these results indicate that the vertebrate PCP pathway regulates CE and hair cell polarity independently and that a p120-catenin-dependent mechanism regulates CE of the cochlea. PMID- 22318629 TI - Dual transcriptional activities of SIX proteins define their roles in normal and ectopic eye development. AB - The SIX family of homeodomain-containing DNA-binding proteins play crucial roles in both Drosophila and vertebrate retinal specification. In flies, three such family members exist, but only two, Sine oculis (So) and Optix, are expressed and function within the eye. In vertebrates, the homologs of Optix (Six3 and Six6) and probably So (Six1 and Six2) are also required for proper eye formation. Depending upon the individual SIX protein and the specific developmental context, transcription of target genes can either be activated or repressed. These activities are thought to occur through physical interactions with the Eyes absent (Eya) co-activator and the Groucho (Gro) co-repressor, but the relative contribution that each complex makes to overall eye development is not well understood. Here, we attempt to address this issue by investigating the role that each complex plays in the induction of ectopic eyes in Drosophila. We fused the VP16 activation and Engrailed repressor domains to both So and Optix, and attempted to generate ectopic eyes with these chimeric proteins. Surprisingly, we find that So and Optix must initially function as transcriptional repressors to trigger the formation of ectopic eyes. Both factors appear to be required to repress the expression of non-retinal selector genes. We propose that during early phases of eye development, SIX proteins function, in part, to repress the transcription of non-retinal selector genes, thereby allowing induction of the retina to proceed. This model of repression-mediated induction of developmental programs could have implications beyond the eye and might be applicable to other systems. PMID- 22318630 TI - Org-1, the Drosophila ortholog of Tbx1, is a direct activator of known identity genes during muscle specification. AB - Members of the T-Box gene family of transcription factors are important players in regulatory circuits that generate myogenic and cardiogenic lineage diversities in vertebrates. We show that during somatic myogenesis in Drosophila, the single ortholog of vertebrate Tbx1, optomotor-blind-related-gene-1 (org-1), is expressed in a small subset of muscle progenitors, founder cells and adult muscle precursors, where it overlaps with the products of the muscle identity genes ladybird (lb) and slouch (slou). In addition, org-1 is expressed in the lineage of the heart-associated alary muscles. org-1 null mutant embryos lack Lb and Slou expression within the muscle lineages that normally co-express org-1. As a consequence, the respective muscle fibers and adult muscle precursors are either severely malformed or missing, as are the alary muscles. To address the mechanisms that mediate these regulatory interactions between Org-1, Lb and Slou, we characterized distinct enhancers associated with somatic muscle expression of lb and slou. We demonstrate that these lineage- and stage-specific cis-regulatory modules (CRMs) bind Org-1 in vivo, respond to org-1 genetically and require T-box domain binding sites for their activation. In summary, we propose that org-1 is a common and direct upstream regulator of slou and lb in the developmental pathway of these two neighboring muscle lineages. Cross-repression between slou and lb and combinatorial activation of lineage-specific targets by Org-1-Slou and Org-1 Lb, respectively, then leads to the distinction between the two lineages. These findings provide new insights into the regulatory circuits that control the proper pattering of the larval somatic musculature in Drosophila. PMID- 22318631 TI - Nematostella vectensis achaete-scute homolog NvashA regulates embryonic ectodermal neurogenesis and represents an ancient component of the metazoan neural specification pathway. AB - achaete-scute homologs (ash) regulate neural development in all bilaterian model animals indicating that they represent a component of the ancestral neurogenic pathway. We test this by investigating four ash genes during development of a basal metazoan, the cnidarian sea anemone Nematostella vectensis. Spatiotemporal expression of ash genes in the early embryo and larval stages suggests that they regulate neurogenesis. More specifically, NvashA is co-expressed with neural genes in the embryonic ectoderm. Knockdown of NvashA results in decreased expression of eight neural markers, including the six novel neural targets identified here. Conversely, overexpression of NvashA induces increased expression of all eight genes, but only within their normal axial domains. Overexpression of NvashB-D differentially increases expression of NvashA targets. The expression patterns and differential ability of ash genes to regulate neural gene expression reveals surprising molecular complexity in these 'simple' animals. These data suggest that achaete-scute homologs functioned in the ancestral metazoan neurogenic pathway and provide a foundation to investigate further the evolution of neurogenesis and the origin of complex central nervous systems. PMID- 22318633 TI - Sharpening of the anterior neural border in the chick by rostral endoderm signalling. AB - The anterior border of the neural plate, presumed to contain the prospective peripheral portion (roof) of the prospective telencephalon, emerges within a vaguely defined proneural ectodermal region. Fate maps carried out at HH4 in the chick reveal that this region still produces indistinctly neural, placodal and non-neural derivatives; it does not express neural markers. We examined how the definitive anterior border domain of the rostral forebrain becomes established and comes to display a neural molecular profile, whereas local non-neural derivatives become separated. The process, interpreted as a border sharpening mechanism via intercalatory cell movements, was studied using fate mapping, time lapse microscopy and in situ hybridization. Separation of neural and non-neural domains proceeds along stages HH4-HH4+, is well advanced at HH5, and is accompanied by a novel dorsoventral intercalation, oriented orthogonal to the border, that distributes transitional cells into molecularly distinct neural and non-neural fields. Meanwhile, neuroectodermal Sox2 expression spreads peripherally from the neighbourhood of the node, reaching the nascent anterior border domain at HH5. We also show that concurrent signals from the endodermal layer are necessary to position and sharpen the neural border, and suggest that FGF8 might be a component of this signalling. PMID- 22318632 TI - Initiation of synapse formation by Wnt-induced MuSK endocytosis. AB - In zebrafish, the MuSK receptor initiates neuromuscular synapse formation by restricting presynaptic growth cones and postsynaptic acetylcholine receptors (AChRs) to the center of skeletal muscle cells. Increasing evidence suggests a role for Wnts in this process, yet how muscle cells respond to Wnt signals is unclear. Here, we show that in vivo, wnt11r and wnt4a initiate MuSK translocation from muscle membranes to recycling endosomes and that this transition is crucial for AChR accumulation at future synaptic sites. Moreover, we demonstrate that components of the planar cell polarity pathway colocalize to recycling endosomes and that this localization is MuSK dependent. Knockdown of several core components disrupts MuSK translocation to endosomes, AChR localization and axonal guidance. We propose that Wnt-induced trafficking of the MuSK receptor to endosomes initiates a signaling cascade to align pre- with postsynaptic elements. Collectively, these findings suggest a general mechanism by which Wnt signals shape synaptic connectivity through localized receptor endocytosis. PMID- 22318634 TI - Non-invasive ventilation in community-acquired pneumonia and severe acute respiratory failure. AB - PURPOSE: The use of non-invasive ventilation (NIV) in severe acute respiratory failure (ARF) due to community-acquired pneumonia (CAP) is controversial, and the risk factors for NIV failure in these patients are not well known. We assessed the characteristics and predictors of outcome of patients with CAP and severe ARF treated with NIV. METHODS: We prospectively assessed 184 consecutive patients; 102 had "de novo" ARF, and 82 previous cardiac or respiratory disease. We defined successful NIV as avoidance of intubation and intensive care unit (ICU) survival at least 24 h in the ward. We assessed predictors of NIV failure and hospital mortality in multivariate analyses. RESULTS: Patients with "de novo" ARF failed NIV more frequently than patients with previous cardiac or respiratory disease (47, 46% versus 21, 26%, p = 0.007). Worsening radiologic infiltrate 24 h after admission, maximum Sepsis-Related Organ Failure Assessment (SOFA) score and, after 1 h of NIV, higher heart rate and lower PaO(2)/FiO(2) and bicarbonate independently predicted NIV failure. Likewise, maximum SOFA, NIV failure and older age independently predicted hospital mortality. Among intubated patients with "de novo" ARF, NIV duration was shorter in hospital survivors than non survivors (32 +/- 24 versus 78 +/- 65 h, p = 0.014). In this group, longer duration of NIV before intubation was associated with decreased hospital survival (adjusted odds ratio 0.978, 95% confidence interval 0.962-0.995, p = 0.012). This association was not observed in patients with previous cardiac or respiratory disease. CONCLUSIONS: Successful NIV was strongly associated with better survival. If predictors for NIV failure are present, avoiding delayed intubation of patients with "de novo" ARF would potentially minimise mortality. PMID- 22318635 TI - Sleep and other factors associated with mental health and psychological distress after intensive care for critical illness. AB - PURPOSE: Some patients who survive intensive care unit (ICU) treatment report psychological sequelae during recovery. This study examined factors associated with psychological outcomes of former ICU patients up to 6 months after hospital discharge. METHODS: Participants (n = 195) were adult survivors of ICU enrolled in a multicenter trial of physical rehabilitation after hospital discharge. The 36-Item Short-Form Health Survey (SF-36), the Impact of Events Scale (IES) and the Depression, Anxiety and Stress Scales were completed, and sleep rated on a five-point scale at weeks 1, 8 and 26; clinical and demographic data were obtained from patient records. RESULTS: Participants were 41% females with mean +/- standard deviation (SD) age of 57 +/- 16 years and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of 19 +/- 7; median lengths of mechanical ventilation and ICU stay were 89 h and 6 days, respectively. Impaired mental health, depression, anxiety, stress and psychological distress significantly improved after week 1. Female gender, younger age and sleeping problems were associated with impaired psychological outcomes on bivariate analyses. Age; gender; week 1 anxiety, depression and stress; week 26 sleeping; and rehabilitation study group were entered into multiple linear regression analyses for week 26 IES and SF-36 Mental Component Summary (MCS) outcomes. IES scores were associated (p < 0.05) with gender, week 1 stress and week 26 sleep but not study group; MCS scores were associated (p < 0.05) with week 1 stress and week 26 sleep but not study group. CONCLUSION: Female gender, early levels of increased stress and problems sleeping are associated with worse psychological recovery for survivors of critical illness. PMID- 22318636 TI - Susceptibilities to amphotericin B, fluconazole and voriconazole of Trichosporon clinical isolates. AB - A total of 35 Trichosporon isolates were collected from the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) project from 1999 to 2006, and their identifications as well as drug susceptibilities were determined. The most frequently isolated species was T. asahii (62.9%), and the most common clinical sample that yielded Trichosporon isolates was urine (37.1%). The etiology of all seven invasive trichosporonosis was T. asahii. For the 22 T. asahii isolates, the MIC(50) and MIC(90) for amphotericin B were 0.25 and 1 MUg/mL, respectively. Those for fluconazole were 2 and 4 MUg/mL, respectively, and for voriconazole 0.031 and 0.063 MUg/mL, respectively. When the intraclass correlation coefficients (ICCs) and agreements were calculated, we found that the MICs of fluconazole obtained from different methods were similar and the inter-method discrepancies were low. Nevertheless, no unanimous MIC of amphotericin B and voriconazole was obtained among different methods. PMID- 22318637 TI - Partial debranching hybrid stent graft for distal aortic arch aneurysms. AB - PURPOSE: To evaluate the early outcomes of treating distal aortic arch aneurysms (DAAAs) with a partial debranching hybrid stent graft, and to analyze the morphology of distances among the supra-aortic branches. METHODS: We used this stent graft to treat DAAA in 12 patients, by debranching the left common carotid artery (LCCA) and the left subclavian artery (LSA). With computed tomography (CT) data on the collective total 28 thoracic aortic aneurysms, the distances from the LSA to the LCCA and those from the LSA to the brachiocephalic artery (BA) were measured using multiplanar reconstruction (MPR) and centerline of flow (CLF) methods. RESULTS: All procedures were done in two stages and all stent grafts were deployed in zone-1. The devices used were the TALENT in seven patients and the TAG in five patients. There were no operative deaths, paraplegia, or type-1 or -3 endoleaks. One patient suffered minor cerebral infarction. The distance from the LSA to the BA was longer than that from the LSA to the LCCA by 10 mm in the CLF method and by 13 mm in the MPR method. CONCLUSIONS: It was possible to achieve a longer proximal landing zone by debranching two supra-aortic branches, the LCCA and the LSA. The partial debranching hybrid stent graft was less invasive and more effective for DAAAs. PMID- 22318638 TI - Necrotizing fasciitis caused by a primary appendicocutaneous fistula. AB - We report a case of necrotizing fasciitis in the loin of a 76-year old man with several coexisting or past health issues, including diabetes mellitus, hypertension, alcohol-related liver cirrhosis, gastrectomy for gastric cancer, subarachnoid hemorrhage, normal pressure hydrocephalus, and cerebral infarction. Incision of the necrotizing fasciitis was successful, but it revealed an appendicocutaneous fistula; thus, we performed appendectomy and fistulectomy. We think that the necrotizing fasciitis was caused by appendicitis perforation involving the retroperitoneum, inducing the formation of an appendicocutaneous fistula. Necrotizing fasciitis and appendicocutaneous fistulae are rare complications of appendicitis. Moreover, to our knowledge, this is the first report of fluoroscopic examination demonstrating that a primary appendicocutaneous fistula had caused necrotizing fasciitis. Our search of the literature found 12 cases of necrotizing fasciitis caused by preoperative appendicitis. We discuss the characteristics and findings of these cases. PMID- 22318644 TI - Platelet-mediated proteolytic down regulation of the anticoagulant activity of protein S in individuals with haematological malignancies. AB - The natural anticoagulant protein S contains a so-called thrombin- sensitive region (TSR), which is susceptible to proteolytic cleavage. We have previously shown that a platelet-associated protease is able to cleave protein S under physiological plasma conditions in vitro . The aim of the present study was to investigate the relation between platelet-associated protein S cleaving activity and in vivo protein S cleavage, and to evaluate the impact of in vivo protein S cleavage on its anticoagulant activity. Protein S cleavage in healthy subjects and in thrombocytopenic and thrombocythaemic patients was evaluated by immunological techniques. Concentration of cleaved and intact protein S was correlated to levels of activated protein C (APC)-dependent and APC-independent protein S anticoagulant activity. In plasma from healthy volunteers 25% of protein S is cleaved in the TSR. While in plasma there was a clear positive correlation between levels of intact protein S and both APC-dependent and APC independent protein S anticoagulant activities, these correlations were absent for cleaved protein S. Protein S cleavage was significantly increased in patients with essential thrombocythaemia (ET) and significantly reduced in patients with chemotherapy-induced thrombocytopenia. In ET patients on cytoreductive therapy, both platelet count and protein S cleavage returned to normal values. Accordingly, platelet transfusion restored cleavage of protein S to normal values in patients with chemotherapy-induced thrombocytopenia. In conclusion, proteases from platelets seem to contribute to the presence of cleaved protein S in the circulation and may enhance the coagulation response in vivo by down regulating the anticoagulant activity of protein S. PMID- 22318645 TI - The role of prostanoid receptors in mediating the effects of PGE3 on human platelet function. PMID- 22318646 TI - Survival following laparoscopic versus open resection for colorectal cancer. AB - BACKGROUND: This study aimed to compare the overall and disease specific survivals of patients who underwent laparoscopic and open resection of colorectal cancer in a high volume tertiary center. METHODS: Consecutive patients who underwent elective resection for colorectal cancer (open resection, n = 1,197; laparoscopic resection, n = 814) from January 2000 to December 2009 were included. The operative details, postoperative complications, postoperative outcomes, and survival data were collected prospectively. Comparison was made between patients who had laparoscopic and open surgery. RESULTS: The age, gender, medical morbidity, and American Society of Anesthesiologists status were similar in the two groups. Laparoscopic resection was associated with significantly less blood loss and a shorter hospital stay. The operating mortality and morbidity were significantly lower in the laparoscopic group. The qualities of the specimens in terms of the distal resection margin and the number of lymph nodes examined were not inferior in the laparoscopic group. With the median follow-up of 40.3 months, the 5-year overall survival (74.1% vs. 65.5%, p < 0.001) and disease specific survival (81.9% vs. 75.2%, p = 0.002) were significantly better in patients with non-disseminated disease in the laparoscopic group. The operative approach was an independent prognostic factor in the overall (risk ratio 1.36, 95% CI 1.093-1.700, p = 0.006) and disease specific (risk ratio 1.32, 95% CI 1.005-1.738, p = 0.048) survivals in multivariate analysis. CONCLUSION: Laparoscopic resection for colorectal cancer is associated with more favorable overall and disease specific survivals when compared with open resection in a high volume tertiary center. PMID- 22318647 TI - Kinetics and mechanism of the reactions of Au(III) complexes with some biologically relevant molecules. AB - The kinetics of the substitution reactions between the mono-functional Au(III) complexes, [Au(dien)Cl](2+) and [Au(terpy)Cl](2+) (dien = 3-azapentane-1,5 diamine, terpy = 2,2';6',2''-terpyridine) and bi-functional Au(III) complexes, [Au(bipy)Cl(2)](+) and [Au(dach)Cl(2)](+) (bipy = 2.2'-bipyridine, dach = (1R,2R) 1,2-diaminocyclohexane) and biologically relevant ligands such as l-histidine (l His), inosine (Ino), inosine-5'-monophosphate (5'-IMP) and guanosine-5' monophosphate (5'-GMP), were studied in detail. All kinetic studies were performed in 25 mM Hepes buffer (pH = 7.2) in the presence of NaCl to prevent the spontaneous hydrolysis of the chloride complexes. The reactions were followed under pseudo-first order conditions as a function of ligand concentration and temperature using stopped-flow UV-vis spectrophotometry. The results showed that the mono-functional complexes react faster than the bi-functional complexes in all studied reactions. The [Au(terpy)Cl](2+) complex is more reactive than the [Au(dien)Cl](2+) complex, which was confirmed by quantum chemical (DFT) calculations. A more than 50% lower activation energy for the terpy than for the dien based complex was found. The bi-functional [Au(bipy)Cl(2)](+) complex is more reactive than the [Au(dach)Cl(2)](+) complex. The reactivity of the studied nucleophiles follows the same order for all studied systems, viz. l-His > 5'-GMP > 5'-IMP > Ino. According to the measured activation parameters, all studied reactions follow an associative substitution mechanism. Quantum chemical calculations (B3LYP/LANL2DZp) suggest that ligand substitution in [Au(terpy)Cl](2+) and [Au(dien)Cl](2+) by imidazole follows an interchange mechanism with a significant degree of associative character. The results demonstrate the strong connection between the reactivity of the complexes toward biologically relevant ligands and their structural and electronic characteristics. Therefore, the binding of gold(III) complexes to 5'-GMP, constituent of DNA, is of particular interest since this interaction is thought to be responsible for their anti-tumour activity. PMID- 22318648 TI - Unrestricted consumption of fruits and vegetables in phenylketonuria: no major impact on metabolic control. AB - BACKGROUND/OBJECTIVES: The treatment of phenylketonuria (PKU) requires consistent restriction of protein intake from natural sources. Therefore, protein from all foods has to be accounted for, even the small amounts in fruits and vegetables. We studied whether free consumption of fruits and vegetables containing less than 75 mg phenylalanine (phe) per 100 g affects metabolic control in children with PKU. SUBJECTS/METHODS: Fourteen children (2-10 years) were included in a cross over study, with a two-week period of conventional treatment (accounting for protein from fruits and vegetables) and a two-week period with free fruit and vegetable consumption. The instruction to follow liberal fruit and vegetable consumption in the first or second study period was randomized. Detailed daily dietary records were obtained throughout the study. Phe and nutrient content was calculated. Dried-blood phe concentration was monitored daily. RESULTS: Although total phe intake increased by an average of 58 mg per day (P=0.037) during the 2 weeks of free fruit and vegetable consumption, dried-blood phe concentrations were unchanged. Total intake of fruits and vegetables did not increase, but patients instead used the higher phe tolerance to consume more of other foods, which were calculated and accounted for. CONCLUSION: Free consumption of fruits and vegetables does not impair metabolic control in PKU patients over a 2-week period. PMID- 22318649 TI - Effect of magnesium supplementation on blood pressure: a meta-analysis. AB - To date, there has been inconclusive evidence regarding the effect of magnesium supplements on blood pressure (BP). This meta-analysis was conducted to assess the effect of magnesium supplementation on BP and to establish the characteristics of trials showing the largest effect size. Primary outcome measures were systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the end of the follow-up period. One hundred and forty-one papers were identified, of which 22 trials with 23 sets of data (n=1173), with 3 to 24 weeks of follow-up met the inclusion criteria, with a supplemented elemental magnesium range of 120-973 mg (mean dose 410 mg). 95% confidence intervals (CI) were calculated using DerSimonian and Laird's random-effects model, with effect size calculated using Hedges G. Combining all data, an overall effect of 0.36 and 0.32 for DBP and SBP, respectively, was observed (95% CI 0.27-0.44 for DBP and 0.23 0.41 for SBP), with a greater effect being seen for the intervention in crossover trials (DBP 0.47, SBP 0.51). Effect size increased in line with increased dosage. Although not all individual trials showed significance in BP reduction, combining all trials did show a decrease in SBP of 3-4 mm Hg and DBP of 2-3 mm Hg, which further increased with crossover designed trials and intake >370 mg/day. To conclude, magnesium supplementation appears to achieve a small but clinically significant reduction in BP, an effect worthy of future prospective large randomised trials using solid methodology. PMID- 22318650 TI - Dietary calcium intake and risk of type 2 diabetes: possible confounding by magnesium. AB - This study examined the association of dietary calcium intake with incident type 2 diabetes by a meta-analysis and explored the potential confounding by magnesium. Potential studies were identified by searching the PubMed database in September 2011. Prospective cohort studies that reported relative risks (RR) with 95% confidence intervals (CI) of type 2 diabetes for dietary calcium intake were selected. Results were combined using either a fixed- or random-effects model. Six prospective cohort studies comprising 264268 participants and 11225 reported cases were included. All combined random-effects meta-analysis yielded a significant pooled RR of 0.85 (95% CI 0.75-0.97). However, a sensitivity analysis limited to four studies with control for magnesium yielded an attenuated, nonsignificant pooled RR of 0.94 (95% CI 0.85-1.05). In conclusion, dietary calcium intake was not independently associated with risk of type 2 diabetes. The inverse association in prior observational studies may be partially confounded by magnesium intake. PMID- 22318651 TI - Late micronutrient deficiency and neurological dysfunction after laparoscopic sleeve gastrectomy: a case report. AB - Although the micronutrient deficiencies and the related neurological manifestations are widely reported after malabsorbitive weight loss surgery, little is known about cerebral dysfunction secondary to micronutrient impairment in subjects undergoing restrictive interventions (that is, sleeve gastrectomy). We describe a case of a 27-year-old woman with a late development of a Wernicke's encephalopathy (WE) and of severe polyneuropathy following a sleeve gastrectomy without any sleeve stenosis. The impact of WE after bariatric surgery is significantly underestimated. Such a risk should be taken into consideration also after restrictive weight loss surgery. Thus, surgeon/clinicians involved in bariatric patients management must be aware of neurological sequelae related to this intervention. PMID- 22318652 TI - Iranian Breast Cancer Bio-Bank: the activity and challenging issues. AB - The information gained from the Human Genome Project has facilitated molecular as well as cellular studies not only to find the origins of Breast Cancer (BC), but also to create novel, and effective treatments. In order to provide an infrastructure for local and international research in this area, Iranian Center for Breast Cancer (ICBC) has established a Bio-Bank (BB) for BC. This article describes the aim, structure, and activities in general, and the challenging issues confronting the bank as a model for the establishment of Bio-Banks in developing countries in particular. The methods employed by the Bank could be explained in the following categories: Blood and Tissue sampling, Preparation and Banking of collected Samples, Clinical and Histopathology data collection, Collaboration Protocol, Challenging issues, and the programs to confront the problems. During the five-year activity of the bank, 110 families were enrolled for genetic counseling, from whom 600 biologic samples were obtained, including 387 blood samples and 213 tissue samples. Of 387 blood samples, 317 (82%) were found to belong to the BC patients and the remaining 70 (18%) belonged to their available relatives. The number of samples increased over the study period partly as a result of the programs designed to confront the problems. During the study period, there were some finished research studies using the samples of BB, and many other studies which are still ongoing. ICBC-BB is a model of biologic sample banking which provides a significant number of biological samples for local and international collaborative research projects regarding molecular and cellular aspects of BC. In establishing the ICBC-BB we have experienced problems and challenges, some general and some local. Some were expected and others not, but we have identified solutions. PMID- 22318653 TI - Tissue banking training courses: Polish experience. AB - Personnel directly involved in the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells should be appropriately qualified and provided with timely and relevant training according to EU directives. In the time of new tissue and cells regulations implementation such a training system existed in Poland only at a local level. The first training programme outlines for various groups of health professionals engaged in tissue banking practice was created in co-operation with the Institute for LifeLong Learning at University of Barcelona in 2006. This initial training courses were financially supported by EU Transition Facility Programme 2004. Then, starting from 2006, based on previous experience, system of advanced training courses was created. This training programme was financially supported by the National Programme for the Development of Transplantation Medicine 2006 2009-POLGRAFT financed by Polish Ministry of Health. During 2006 and 2007 first set of tissue banking initial training courses were provided according to TF 2004 project. Over 200 pathologists, forensic medicine specialists and other medical doctors responsible for donor screening and classification, medical directors of tissue establishments, technical staff; tissue graft users: orthopaedic surgeons, neurosurgeons, cardiosurgeons and ophthalmologists were trained. Between 2006 and 2009 there were organized 8 advanced tissue banking training courses according to POLGRAFT programme. There were organized both theoretical and practical courses on various aspects of tissue for over 350 persons. We present our experience in organisation of international and national tissue banking training courses. PMID- 22318654 TI - Variable composition of heme oxygenases with different regiospecificities in Pseudomonas species. AB - Heme oxygenases (HO) degrade heme yielding iron, carbon monoxide and one of four possible biliverdin (BV) isomers. Pseudomonas aeruginosa PAO1 is thus far the only organism to contain two HOs with different regiospecificities: BphO and PigA. While BphO cleaves heme to exclusively yield BV IXalpha, PigA produces the BV isomers IXbeta and IXdelta. We bioinformatically identified putative HOs in diverse Pseudomonas strains, tested their enzymatic functionality and determined their regiospecificity. Surprisingly, even high amino acid sequence identities to the P. aeruginosa HOs were not sufficient to correctly predict the HO regiospecificity in all cases. Based on our results, Pseudomonas strains differ in their HO composition containing either BphO or PigA or both HO types. Concomitantly with the existence of bphO is the occurrence of at least one gene encoding a bacterial phytochrome implying that only BV IXalpha is the sufficient phytochrome chromophore. In contrast, pigA genes are organized in gene clusters associated with iron utilization implying a role of PigA in iron acquisition. However, at least in strains containing no PigA this function maybe fulfilled by BphO. Only a combination of homology searches and analyses of genetic environments is appropriate for a reliable prediction of the regiospecificity of Pseudomonas HOs. PMID- 22318655 TI - The interplay of structural and optical properties in individual ZnO nanostructures. AB - Semiconductor nanostructures exhibit unique properties distinct from their bulk counterparts by virtue of nanoscale dimensions; in particular, exceptionally large surface area-to-volume ratios relative to that of the bulk produce variations in surface state populations that have numerous consequences on materials properties. Of the low-dimensional semiconductor nanostructures, nanowires offer a unique prospect in nanoscale optoelectronics due to their one dimensional architecture. Already, many devices based upon individual nanowires have been demonstrated, but questions about how nano-size and structural variations affect the underlying materials properties still remain unanswered. Here, we focus on understanding the growth mechanism and kinetics of ZnO nanowires and related nanowalls, and their effects on nanoscale structural and optical properties. PMID- 22318656 TI - Interindividual variability in hepatic expression of the multidrug resistance associated protein 2 (MRP2/ABCC2): quantification by liquid chromatography/tandem mass spectrometry. AB - Multidrug-associated protein 2 (MRP2) is an efflux transporter that is expressed at the bile canalicular membrane. To allow in vitro to in vivo extrapolation of the contribution of MRP2 toward hepatic disposition of its substrates, data on the interindividual variability of hepatic MRP2 protein expression are required. Therefore, we quantified the expression of MRP2 in the University of Washington (UW) human liver bank (n = 51) using a modified version of a previously validated liquid chromatography/tandem mass spectrometry assay. An unlabeled (LTIIPQDPILFSGSLR) and stable isotope-labeled (LTIIPQDPILFSGSL[(13)C(6)(15)N(1)]R) surrogate peptide for MRP2 were used as the calibrator and internal standard, respectively. After isolation of the membrane fraction from the liver tissue, in-solution tryptic digestion was conducted. Quality control samples created by spiking human serum albumin or pooled human liver (n = 51) matrix with three different MRP2 synthetic peptide concentrations generated error and precision values of less than 15%. As determined by the surrogate peptide, the average MRP2 expression in the UW liver bank samples was 1.54 +/- 0.64 fmol/MUg liver membrane protein and was found to be independent of age (7-63 years) or sex. A single nucleotide polymorphism in the promoter region (rs717620), previously thought to affect MRP2 expression, did not influence hepatic expression of MRP2. In contrast, the single nucleotide polymorphism 21214G>A (V417I; rs2273697) was associated with significantly higher hepatic MRP2 expression. PMID- 22318657 TI - Adiposity, insulin resistance and cardiovascular risk factors in 9-10-year-old Indian children: relationships with birth size and postnatal growth. AB - Lower birthweight, and rapid childhood weight gain predict elevated cardiovascular risk factors in children. We examined associations between serial, detailed, anthropometric measurements from birth to 9.5 years of age and cardiovascular risk markers in Indian children. Children (n = 663) born at the Holdsworth Memorial Hospital, Mysore, India were measured at birth and 6-12 monthly thereafter. At 9.5 years, 539 (255 boys) underwent a 2-h oral glucose tolerance test, and blood pressure (BP) and fasting lipid concentrations were measured. Insulin resistance was calculated using the HOMA equation. These outcomes were examined in relation to birth measurements and changes in measurements (growth) during infancy (0-2 years), 2-5 years and 5-9.5 years using conditional s.d. scores. Larger current weight, height and skinfold thickness were associated with higher risk markers at 9.5 years (P < 0.05). Lower weight, smaller length and mid-arm circumference at birth were associated with higher fasting glucose concentrations at 9.5 years (P ? 0.01). After adjusting for current weight/height, there were inverse associations between birthweight and/or length and insulin concentrations, HOMA, systolic and diastolic BP and plasma triglycerides (P < 0.05). Increases in conditional weight and height between 0-2, 2-5 and 5-9.5 years were associated with higher insulin concentrations, HOMA and systolic BP. In conclusion, in 9-10-year-old Indian children, as in other studies, cardiovascular risk factors were highest in children who were light or short at birth but heavy or tall at 9 years. Greater infant and childhood weight and height gain were associated with higher risk markers. PMID- 22318658 TI - A histopathological diagnostic marker for human spinal astrocytoma: expression of glial fibrillary acidic protein-delta. AB - Although histopathological diagnosis of spinal cord astrocytomas is important for postoperative treatment planning and prognosis, there is a lack of reliable immunohistochemical markers. The purpose of our study was to assess the expression pattern of GFAP-delta in spinal cord astrocytomas in human patients and to evaluate the utility of GFAP-delta as an immunohistochemical diagnostic marker. A total of 22 patients with spinal cord astrocytic tumors were included in this study. Patients were classified according to the WHO designation of human astrocytic tumors; three patients had grade 1 astrocytomas, 14 had grade 2, and five had Grade 3. Normal control spinal cord tissues were obtained at autopsy from the cervical spinal cords of ten patients with no history of cervical trauma or neurological disease. We evaluated BRAF, IDH1, GFAP, and GFAP-delta immunoreactivity in control tissues and astrocytomas. In normal control tissues, GFAP immunoreactivity was detected in astrocytes whereas GFAP-delta immunoreactivity was observed in very few astrocytes adjacent to the subpial layer of the spinal cord. GFAP-delta immunoreactivity was significantly correlated with spinal cord astrocytoma grade in astrocytomas compared to that in normal control tissues. The optical density of GFAP-delta increased significantly with astrocytoma grade (correlation coefficient, R (2) = 0.680). Also, BRAF and IDH1 immunoreactivity were detected in astrocytoma. We suggest that GFAP-delta may be an additional, reliable histopathological diagnostic marker for spinal cord astrocytomas. PMID- 22318659 TI - Ecological segregation drives fine-scale cytotype distribution of Senecio carniolicus in the Eastern Alps. AB - In order to uncover patterns and processes of segregation of co-existing cytotypes, we investigated a zone in the eastern Alps (Austria) where diploid and hexaploid individuals of the alpine herb Senecio carniolicus Willd. (Asteraceae) co-occur. Linking the fine-scale distribution of cytotypes to environmental and spatial factors revealed segregation along an ecological gradient, which was also reflected in the cytotype-associated plant assemblages. Compared to diploids, hexaploids are found in more species-rich and denser communities. This may be due to their better competitive ability and lower tolerance of abiotic stress compared to the diploids. The lack of any intermediate cytotypes suggests the presence of strong reproductive isolation mechanisms, whose nature is, however, elusive. PMID- 22318660 TI - Comparison of cognitive decline between dementia with Lewy bodies and Alzheimer's disease: a cohort study. AB - OBJECTIVES: Dementia with Lewy bodies (DLB) accounts for 10%-15% of dementia cases at autopsy and has distinct clinical features associated with earlier institutionalisation and a higher level of carer distress than are seen in Alzheimer's disease (AD). At present, there is on-going debate as to whether DLB is associated with a more rapid cognitive decline than AD. An understanding of the rate of decline of cognitive and non-cognitive symptoms in DLB may help patients and carers to plan for the future. DESIGN: In this cohort study, the authors compared 100 AD and 58 DLB subjects at baseline and at 12-month follow-up on cognitive and neuropsychiatric measures. SETTING: Patients were recruited from 40 European centres. PARTICIPANTS: Subjects with mild-moderate dementia. Diagnosis of DLB or AD required agreement between consensus panel clinical diagnosis and visual rating of 123I-FP-CIT (dopamine transporter) single photon emission computed tomography neuroimaging. OUTCOME MEASURES: The Cambridge Cognitive Examination including Mini-Mental State Examination and Neuropsychiatric Inventory (NPI). RESULTS: The AD and DLB groups did not differ at baseline in terms of age, gender, Clinical Dementia Rating score and use of cholinesterase inhibitors or memantine. NPI and NPI carer distress scores were statistically significantly higher for DLB subjects at baseline and at follow-up, and there were no differences between AD and DLB in cognitive scores at baseline or at follow-up. There was no significant difference in rate of progression of any of the variables analysed. CONCLUSIONS: DLB subjects had more neuropsychiatric features at baseline and at follow-up than AD, but the authors did not find any statistically significant difference in rate of progression between the mild-moderate AD and DLB groups on cognitive or neuropsychiatric measures over a 12-month follow-up period. PMID- 22318661 TI - Clinical decision making in a high-risk primary care environment: a qualitative study in the UK. AB - OBJECTIVE: Examine clinical reasoning and decision making in an out of hours (OOH) primary care setting to gain insights into how general practitioners (GPs) make clinical decisions and manage risk in this environment. DESIGN: Semi structured interviews using open-ended questions. SETTING: A 2-month qualitative interview study conducted in Oxfordshire, UK. PARTICIPANTS: 21 GPs working in OOH primary care. RESULTS: The most powerful themes to emerge related to dealing with urgent potentially high-risk cases, keeping patients safe and responding to their needs, while trying to keep patients out of hospital and the concept of 'fire fighting'. There were a number of well-defined characteristics that GPs reported making presentations easy or difficult to deal with. Severely ill patients were straightforward, while the older people, with complex multisystem diseases, were often difficult. GPs stopped collecting clinical information and came to clinical decisions when high-risk disease and severe illness requiring hospital attention has been excluded; they had responded directly to the patient's needs and there was a reliable safety net in place. Learning points that GPs identified as important for trainees in the OOH setting included the importance of developing rapport in spite of time pressures, learning to deal with uncertainty and learning about common presentations with a focus on critical cues to exclude severe illness. CONCLUSIONS: The findings support suggestions that improvements in primary care OOH could be achieved by including automated and regular timely feedback system for GPs and individual peer and expert clinician support for GPs with regular meetings to discuss recent cases. In addition, trainee support and mentoring to focus on clinical skills, knowledge and risk management issues specific to OOH is currently required. Investigating the stopping rules used for diagnostic closure may provide new insights into the root causes of clinical error in such a high-risk setting. PMID- 22318662 TI - Treading carefully: a qualitative ethnographic study of the clinical, social and educational uses of exercise ECG in evaluating stable chest pain. AB - OBJECTIVE: To examine functions of the exercise ECG in the light of the recent National Institute for Health and Clinical Excellence guidelines recommending that it should not be used for the diagnosis or exclusion of stable angina. DESIGN: Qualitative ethnographic study based on interviews and observations of clinical practice. SETTING: 3 rapid access chest pain clinics in England. PARTICIPANTS: Observation of 89 consultations in chest pain clinics, 18 patient interviews and 12 clinician interviews. MAIN OUTCOME MEASURE: Accounts and observations of consultations in chest pain clinics. RESULTS: The exercise ECG was observed to have functions that extended beyond diagnosis. It was used to clarify a patient's story and revise the initial account. The act of walking on the treadmill created an additional opportunity for dialogue between clinician and patient and engagement of the patient in the diagnostic process through precipitation of symptoms and further elaboration of symptoms. The exercise ECG facilitated reassurance in relation to exercise capacity and tolerance, providing a platform for behavioural advice particularly when exercise was promoted by the clinician. CONCLUSIONS: Many of the practices that have been built up around the use of the exercise ECG are potentially beneficial to patients and need to be considered in the re-design of services without that test. Through its contribution to the patient's history and to subsequent advice to the patient, the exercise ECG continues to inform the specialist assessment and management of patients with new onset stable chest pain, beyond its now marginalised role in diagnosis. PMID- 22318663 TI - Change in physical activity and weight in relation to retirement: the French GAZEL Cohort Study. AB - OBJECTIVES: To examine the trajectories of physical activity from preretirement to postretirement and to further clarify whether the changes in physical activity are associated with changes in body weight. DESIGN: Prospective. SETTING: French national gas and electricity company (GAZEL cohort). PARTICIPANTS: From the original sample of 20 625 employees, only those retiring between 2001 and 2008 on a statutory basis were selected for the analyses (analysis 1: n=2711, 63% men; analysis 2: n=3812, 75% men). Persons with data on at least one preretirement and postretirement measurement of the outcome were selected. PRIMARY AND SECONDARY OUTCOME MEASURES: All outcome data were gathered by questionnaires. In analysis 1, the annual prevalence of higher physical activity (walking >=5 km/week) 4 years before and after retirement was analysed. In analysis 2, changes in leisure time sport activities (engagement, frequency and manner) from preretirement to postretirement were analysed with simultaneous changes in body weight (kilogram). RESULTS: In analysis 1 (n=2711), prevalence estimates for 4 years before and 4 years after retirement showed that higher leisure-time physical activity (walking at least 5 km/week) increased by 36% in men and 61% in women during the transition to retirement. This increase was also observed among people at a higher risk of physical inactivity, such as smokers and those with elevated depressive symptoms. In a separate sample (analysis 2, n=3812), change in weight as a function of preretirement and postretirement physical activity was analysed. Weight gain preretirement to postretirement was 0.85 (95% CI 0.48 to 1.21) to 1.35 (0.79 to 1.90) kg greater among physically inactive persons (decrease in activity or inactive) compared with those physically active (p<0.001). CONCLUSIONS: Retirement transition may be associated with beneficial changes in lifestyle and may thus be a good starting point to preventive interventions in various groups of individuals in order to maintain long-term changes. PMID- 22318664 TI - A qualitative study of manufacturers' submissions to the UK NICE single technology appraisal process. AB - OBJECTIVES: As part of the National Institute for Health and Clinical Excellence (NICE) Single Technology Appraisal (STA) process, manufacturers present submissions outlining the clinical and cost-effectiveness of new technologies. These submissions are critically appraised by Evidence Review Groups (ERGs), who produce a report, which forms part of the evidence considered by the NICE Appraisal Committees. The purpose of this research was first to identify common issues and concerns identified by the ERGs in their analyses of manufacturers' submissions (MS). The aim was then to use these as a basis to develop feedback for manufacturers. DESIGN: A qualitative study using a content analysis approach to examine two sources of evidence, the first 30 ERG reports and 21 clarification letters associated with these STAs. SETTING: UK HTA programme. PRIMARY AND SECONDARY OUTCOME MEASURES: Common issues and concerns in MS. RESULTS: There were positive comments regarding the quality of the MS, many of which were clearly written. The majority, however, were generally of poor quality and issues and concerns identified across the ERG reports and clarification letters included: criticisms related to the data being used especially data employed in the cost effectiveness model, failure to perform a necessary analysis and poor reporting of processes used in the MS. Aspects of the decision problem were also often poorly or inadequately addressed by manufacturers. The majority of points raised for clarification related to the economic data analysis. Internal inconsistencies between the clinical and economic sections of the submission were frequently highlighted. These were used as the basis for the development of 12 suggestions for manufacturers. CONCLUSIONS: Much can be done to improve the quality of MS in the NICE STA process. Suggestions include the need for clear and transparent reporting of methods and analyses. PMID- 22318665 TI - Clustering of substance use and sexual risk behaviour in adolescence: analysis of two cohort studies. AB - OBJECTIVES: The authors aimed to examine whether changes in health risk behaviour rates alter the relationships between behaviours during adolescence, by comparing clustering of risk behaviours at different time points. DESIGN: Comparison of two cohort studies, the Twenty-07 Study ('earlier cohort', surveyed in 1987 and 1990) and the 11-16/16+ Study ('later cohort', surveyed 1999 and 2003). SETTING: Central Clydeside Conurbation around Glasgow City. PARTICIPANTS: Young people who participated in the Twenty-07 and 11-16/16+ studies at ages 15 and 18-19. PRIMARY AND SECONDARY OUTCOMES MEASURES: The authors analysed data on risk behaviours in both early adolescence (started smoking prior to age 14, monthly drinking and ever used illicit drugs at age 15 and sexual intercourse prior to age 16) and late adolescence (age 18-19, current smoking, excessive drinking, ever used illicit drugs and multiple sexual partners) by gender and social class. RESULTS: Drinking, illicit drug use and risky sexual behaviour (but not smoking) increased between the earlier and later cohort, especially among girls. The authors found strong associations between substance use and sexual risk behaviour during early and late adolescence, with few differences between cohorts, or by gender or social class. Adjusted ORs for associations between each substance and sexual risk behaviour were around 2.00. The only significant between-cohort difference was a stronger association between female early adolescent smoking and early sexual initiation in the later cohort. Also, relationships between illicit drug use and both early sexual initiation and multiple sexual partners in late adolescence were significantly stronger among girls than boys in the later cohort. CONCLUSIONS: Despite changes in rates, relationships between adolescent risk behaviours remain strong, irrespective of gender and social class. This indicates a need for improved risk behaviour prevention in young people, perhaps through a holistic approach, that addresses the broad shared determinants of various risk behaviours. PMID- 22318666 TI - Incentivising safe sex: a randomised trial of conditional cash transfers for HIV and sexually transmitted infection prevention in rural Tanzania. AB - OBJECTIVE: The authors evaluated the use of conditional cash transfers as an HIV and sexually transmitted infection prevention strategy to incentivise safe sex. DESIGN: An unblinded, individually randomised and controlled trial. SETTING: 10 villages within the Kilombero/Ulanga districts of the Ifakara Health and Demographic Surveillance System in rural south-west Tanzania. PARTICIPANTS: The authors enrolled 2399 participants, aged 18-30 years, including adult spouses. INTERVENTIONS: Participants were randomly assigned to either a control arm (n=1124) or one of two intervention arms: low-value conditional cash transfer (eligible for $10 per testing round, n=660) and high-value conditional cash transfer (eligible for $20 per testing round, n=615). The authors tested participants every 4 months over a 12-month period for the presence of common sexually transmitted infections. In the intervention arms, conditional cash transfer payments were tied to negative sexually transmitted infection test results. Anyone testing positive for a sexually transmitted infection was offered free treatment, and all received counselling. MAIN OUTCOME MEASURES: The primary study end point was combined prevalence of the four sexually transmitted infections, which were tested and reported to subjects every 4 months: Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and Mycoplasma genitalium. The authors also tested for HIV, herpes simplex virus 2 and syphilis at baseline and month 12. RESULTS: At the end of the 12-month period, for the combined prevalence of any of the four sexually transmitted infections, which were tested and reported every 4 months (C trachomatis, N gonorrhoeae, T vaginalis and M genitalium), unadjusted RR for the high-value conditional cash transfer arm compared to controls was 0.80 (95% CI 0.54 to 1.06) and the adjusted RR was 0.73 (95% CI 0.47 to 0.99). Unadjusted RR for the high-value conditional cash transfer arm compared to the low-value conditional cash transfer arm was 0.76 (95% CI 0.49 to 1.03) and the adjusted RR was 0.69 (95% CI 0.45 to 0.92). No harm was reported. CONCLUSIONS: Conditional cash transfers used to incentivise safer sexual practices are a potentially promising new tool in HIV and sexually transmitted infections prevention. Additional larger study would be useful to clarify the effect size, to calibrate the size of the incentive and to determine whether the intervention can be delivered cost effectively. TRIAL REGISTRATION NUMBER: NCT00922038 ClinicalTrials.gov. PMID- 22318667 TI - Does landmark selection affect the reliability of tibial tubercle-trochlear groove measurements using MRI? AB - BACKGROUND: A lateralized tibial tubercle is one potential cause of patellar instability. The tibial tubercle-trochlear groove (TT-TG) distance using CT is a reliable measure and considered the gold standard. Using MRI for this purpose has increased, although the reliability of doing so is not well studied. QUESTIONS/PURPOSES: We sought to (1) determine variability in the insertion of the patellar tendon relative to the tibial tubercle and whether this affects the measurement on MRI of the traditional TT-TG distance versus the functional patellar tendon-trochlear groove (PT-TG) distance, (2) determine the reliability of measuring the osseous TT-TG distance, (3) determine the reliability of measuring the soft tissue PT-TG distance, and (4) compare the reliabilities of using osseous (TT-TG) versus soft tissue (PT-TG) landmarks. METHODS: Four observers measured the TT-TG and the PT-TG distances of 50 MR images of knees obtained for any reason. Each observer repeated these measurements 30 days later. The interobserver and intraobserver reliabilities, measurements per observer that varied from the group mean by greater than 2 mm, and the limit of agreement were calculated. RESULTS: The TT-TG and PT-TG differed by as little as 0.11 mm and by as much as 4.18 mm with an average difference of 1.37 mm. The interobserver and intraobserver reliabilities were greater than 90% for the PT-TG and TT-TG distances. The PT-TG distance was less variable in that this measurement showed interobserver and intraobserver reliabilities of 0.977 and 0.972 respectively, versus 0.913 and 0.961 for the TT-TG measurement. Additionally, the PT-TG measurements resulted in a lower average difference to the mean for each observer, less number of knees per observer where the difference to the mean was greater than 2 mm, and improved limit of agreement. CONCLUSIONS: The TT-TG and the PT-TG distances were not identical and differed by as much as 4.18 mm; as such they are not interchangeable when measuring this distance. Both methods are reliable for measuring lateral offset of the extensor mechanism, but the use of soft tissue landmarks is less variable and thus would provide a more reliable measurement for surgical planning. LEVEL OF EVIDENCE: Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID- 22318668 TI - Can lumbopelvic fixation salvage unstable complex sacral fractures? AB - BACKGROUND: Traditional screw or plate fixation options can be used to fix the majority of sacral fractures. However, these techniques are unreliable with dysmorphic upper sacral segments, U-fractures, osseous compression of neural elements, and previously failed fixation. Lumbopelvic fixation can potentially address these injuries but is a technically demanding procedure requiring spinal and pelvic fixation and it is unclear whether it reliably corrects the deformity and restores function. QUESTIONS/PURPOSES: We therefore assessed reduction quality and loss of fixation, pain related to prominent hardware, subjective dysfunction measured by the Short Musculoskeletal Function Assessment (SMFA), and complications. METHODS: We retrospectively reviewed 15 patients with unstable sacral fractures treated with lumbopelvic fixation between 2002 and 2010. Patients had radiographic monitoring regarding reduction quality and loss of fixation and clinical followup using the SMFA. The minimum followup was 12 months (mean, 23 months; range, 12-41 months). RESULTS: Posterior reduction quality was 11 of 15 with less than 5 mm persistent displacement and four of 15 with 5 to 10 mm displacement. Loss of fixation was observed in one patient as a result of a technical error. Prominent hardware resulted in greater pain. Despite daily activity and bother subscores improving over time, we found long-term dysfunction in the SMFA. Eleven of the 15 patients were able to return to previous work or activities. CONCLUSION: Complex posterior pelvic ring injuries of the sacrum not amenable to traditional fixation options can be salvaged with adherence to the technical details of lumbopelvic fixation. Hardware prominence and pain are markedly reduced with screw head recession. Long-term impairment is noted in patients with complex pelvic ring injuries requiring lumbopelvic fixation compared with normative data. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 22318669 TI - Disruption of PF4/H multimolecular complex formation with a minimally anticoagulant heparin (ODSH). AB - Recent studies have shown that ultra-large complexes (ULCs) of platelet factor 4 (PF4) and heparin (H) play an essential role in the pathogenesis of heparin induced thrombocytopenia (HIT), an immune-mediated disorder caused by PF4/H antibodies. Because antigenic PF4/H ULCs assemble through non-specific electrostatic interactions, we reasoned that disruption of charge-based interactions can modulate the immune response to antigen. We tested a minimally anticoagulant compound (2-O, 3-O desulfated heparin, ODSH) with preserved charge to disrupt PF4/H complex formation and immunogenicity. We show that ODSH disrupts complexes when added to pre-formed PF4/H ULCs and prevents ULC formation when incubated simultaneously with PF4 and UFH. In other studies, we show that excess ODSH reduces HIT antibody (Ab) binding in immunoassays and that PF4/ODSH complexes do not cross-react with HIT Abs. When ODSH and unfractionated heparin (UFH) are mixed at equimolar concentrations, we show that there is a negligible effect on amount of protamine required for heparin neutralisation and reduced immunogenicity of PF4/UFH in the presence of ODSH. Taken together, these studies suggest that ODSH can be used concurrently with UFH to disrupt PF4/H charge interactions and provides a novel strategy to reduce antibody mediated complications in HIT. PMID- 22318670 TI - Double 1,4-rhodium migration cascade in rhodium-catalysed arylative ring opening/spirocyclisation of (3-arylcyclobutylidene)acetates. AB - 1,4-Rhodium migration occurs twice during the course of the rhodium-catalysed arylative ring-opening/spirocyclisation reaction of (3 arylcyclobutylidene)acetates with sodium tetraarylborates to afford ketones possessing a 1,1'-spirobiindane skeleton. PMID- 22318671 TI - Identification of structural defects in graphitic materials by gas-phase anisotropic etching. AB - We developed a method of identifying the structural defects in graphitic materials by an anisotropic etching technique. Intrinsic and oxygen- or argon- plasma induced artificial defects' density and domain size can be obtained easily and precisely. It was inferred, through our investigations, that the grade ZYA highly oriented pyrolytic graphite (HOPG) sample has a better crystal quality, with a lower defect density, while the Kish graphite has a larger grain size and higher defect density. Defect types and lattice orientations can also be extracted by this technique. Furthermore, this method could apply to various graphitic materials including graphene. PMID- 22318672 TI - Etiology and epidemiology of viral diarrhea in children under the age of five hospitalized in Tianjin, China. AB - Viral diarrhea is a great threat to children's health in developing countries. We conducted a prospective surveillance study of acute diarrhea of young children at Tianjin Children's Hospital from April 2008 to April 2009. Viral infections were detected in 356 of the total 766 collected stool specimens (46.48%). Rotavirus infections were the most common (27.94%; predominant type G1), followed by adenovirus infections (17.62%; predominant type Ad41), norovirus infections (5.87%; predominant type GII-4/2006 b), and astrovirus infections (3.15%; only HAstV-1). Children younger than 1 year old were the most susceptible population to viral infections (87.9%). Diarrhea, vomiting, and fever were the most frequent clinical symptoms among the infected patients. The viral infections had no age, sex, or regional differences. Most infection rates were higher in the autumn, winter, and spring. This study supported that the rotavirus vaccine should be included in the Expanded Programme on Immunization in China. PMID- 22318673 TI - Sex-specific time trends in first admission to hospital for peripheral artery disease in Scotland 1991-2007. AB - BACKGROUND: This study examined trends for all first hospital admissions for peripheral artery disease (PAD) in Scotland from 1991 to 2007 using the Scottish Morbidity Record. METHODS: First admissions to hospital for PAD were defined as an admission to hospital (inpatient and day-case) with a principal diagnosis of PAD, with no previous admission to hospital (principal or secondary diagnosis) for PAD in the previous 10 years. RESULTS: From 1991 to 2007, 41,593 individuals were admitted to hospital in Scotland for the first time for PAD. Some 23,016 (55.3 per cent) were men (mean(s.d.) age 65.7(11.7) years) and 18,577 were women (aged 70.4(12.8) years). For both sexes the population rate of first admissions to hospital for PAD declined over the study interval: from 66.7 per 100,000 in 1991-1993 to 39.7 per 100,000 in 2006-2007 among men, and from 43.5 to 29.1 per 100,000 respectively among women. After adjustment, the decline was estimated to be 42 per cent in men and 27 per cent in women (rate ratio for 2007 versus 1991: 0.58 (95 per cent confidence interval 0.55 to 0.62) in men and 0.73 (0.68 to 0.78) in women). The intervention rate fell from 80.8 to 74.4 per cent in men and from 77.9 to 64.9 per cent in women. The proportion of hospital admissions as an emergency or transfer increased, from 23.9 to 40.7 per cent among men and from 30.0 to 49.5 per cent among women. CONCLUSION: First hospital admission for PAD in Scotland declined steadily and substantially between 1991 and 2007, with an increase in the proportion that was unplanned. PMID- 22318674 TI - Restoration of dystrophin expression using the Sleeping Beauty transposon. AB - The Sleeping beauty (SB) system is a non-viral DNA based vector that has been used to stably integrate therapeutic genes into disease models. Here we report the SB system is capable of stably integrating the DeltaR4-R23/CTDelta micro dystrophin gene into a conditionally immortal dystrophin deficient muscle cell line, H2K SF1, a murine cell model for Duchenne muscular dystrophy. Genetically corrected H2K SF1 cells retained their myogenic properties in vitro. Moreover, upon transplantation DeltaR4-R23/CTDelta micro-dystrophin expression was detected within mdx nu/nu mice. Our data suggests the SB system is an effective way of stably integrating therapeutic genes into myogenic cells. PMID- 22318675 TI - Mortality in a cardiac intensive care unit. AB - OBJECTIVE: There are no reliable data on mortality and morbidity of adult patients in modern university-based cardiac intensive care units. Therefore, the present study was aimed to provide complete data in respect to mortality and morbidity of all patients admitted between 1 January 2008 and 31 December 2009 to the newly opened cardiac intensive care unit of the Heart Centre of the Cologne University Hospital. METHODS: All patients admitted to the 6-bed intensive care unit of the Heart Centre of the University of Cologne between January 1 2008 and December 31 2009 were included in this study. RESULTS: A total of 684 patients were investigated. The majority of patients (71.1%) were male. The overall in hospital mortality was 32.5%. The most frequent diagnosis was acute coronary syndrome (43.6%). Coronary angiography was performed in 45.5% of all patients. Cardiopulmonary resuscitation was the reason for admission in 30.8%, the in hospital mortality of those patients (46.0%) was much higher compared to the overall mortality. CONCLUSIONS: Our data demonstrate that despite state-of-the art university-based intensive care medicine with modern equipment the mortality remains high. These findings will help in calculating the resources required to meet the increasing demand for intensive care medicine. PMID- 22318677 TI - Duckweed rising at Chengdu: summary of the 1st International Conference on Duckweed Application and Research. AB - Duckweeds, plants of the Lemnaceae family, have the distinction of being the smallest angiosperms in the world with the fastest doubling time. Together with its naturally ability to thrive on abundant anthropogenic wastewater, these plants hold tremendous potential to helping solve critical water, climate and fuel issues facing our planet this century. With the conviction that rapid deployment and optimization of the duckweed platform for biomass production will depend on close integration between basic and applied research of these aquatic plants, the first International Conference on Duckweed Research and Applications (ICDRA) was organized and took place in Chengdu, China, from October 7th to 10th of 2011. Co-organized with Rutgers University of New Jersey (USA), this Conference attracted participants from Germany, Denmark, Japan, Australia, in addition to those from the US and China. The following are concise summaries of the various oral presentations and final discussions over the 2.5 day conference that serve to highlight current research interests and applied research that are paving the way for the imminent deployment of this novel aquatic crop. We believe the sharing of this information with the broad Plant Biology community is an important step toward the renaissance of this excellent plant model that will have important impact on our quest for sustainable development of the world. PMID- 22318676 TI - The Arabidopsis thaliana transcriptional activator STYLISH1 regulates genes affecting stamen development, cell expansion and timing of flowering. AB - SHORT-INTERNODES/STYLISH (SHI/STY)-family proteins redundantly regulate development of lateral organs in Arabidopsis thaliana. We have previously shown that STY1 interacts with the promoter of the auxin biosynthesis gene YUCCA (YUC)4 and activates transcription of the genes YUC4, YUC8 and OCTADECANOID-RESPONSIVE ARABIDOPSIS AP2/ERF (ORA)59 independently of protein translation. STY1 also affects auxin levels and auxin biosynthesis rates. Here we show that STY1 induces the transcription of 16 additional genes independently of protein translation. Several of these genes are tightly co-expressed with SHI/STY-family genes and/or down-regulated in SHI/STY-family multiple mutant lines, suggesting them to be regulated by SHI/STY proteins during plant development. The majority of the identified genes encode transcription factors or cell expansion-related enzymes and functional studies suggest their involvement in stamen and leaf development or flowering time regulation. PMID- 22318678 TI - Role of early growth response 1 in arteriogenesis: impact on vascular cell proliferation and leukocyte recruitment in vivo. AB - Based on previous findings that early growth response 1 (Egr-1) participates in leukocyte recruitment and cell proliferation in vitro, this study was designed to investigate its mode of action during arteriogenesis in vivo. In a model of peripheral arteriogenesis, Egr-1 was significantly upregulated in growing collaterals of wild-type (WT) mice, both on mRNA and protein level. Egr-1(-/-) mice demonstrated delayed arteriogenesis after femoral artery ligation. They further showed increased levels of monocytes and granulocytes in the circulation, but reduced levels in adductor muscles under baseline conditions. After femoral artery ligation, elevated numbers of macrophages were detected in the perivascular zone of collaterals in Egr-1(-/-) mice and mRNA of leukocyte recruitment mediators was upregulated. Other Egr family members (Egr-2 to -4) were significantly upregulated only in Egr-1(-/-) mice, suggesting a mechanism of counterbalancing Egr-1 deficiency. Moreover, splicing factor-1, downregulated in WT mice after femoral artery ligation in the process of increased vascular cell proliferation, was upregulated in Egr-1(-/-) mice. alphaSM-actin on the other hand, significantly downregulated in WT mice, showed no differential expression in Egr-1(-/-) mice. While cell cycle regulator cyclin E and cdc20 were upregulated in Egr-1(-/-) mice, cyclin D1 expression decreased below the detection limit in collaterals, and the proliferation marker ki67 was not differentially expressed. In conclusion, compensation for deficiency in Egr-1 function in leukocyte recruitment can presumably be mediated by other transcription factors; however, Egr-1 is indispensable for effective vascular cell cycle progression in arteriogenesis. PMID- 22318684 TI - Solvent-induced single-crystal to single-crystal transformation of a 2D coordination network to a 3D metal-organic framework greatly enhances porosity and hydrogen uptake. AB - Exposure to CH(2)Cl(2) at room temperature induces single-crystal to single crystal transformation of the 2D coordination network [Zn(2)L(DMF)(4)].2DMF.4H(2)O to the 3D metal-organic framework [Zn(2)L(H(2)O)(2)].xsolv via dimerization of the metal-connecting points, leading to significant enhancement in framework stability, porosity, and H(2) uptake capacity. PMID- 22318685 TI - Role of transcriptional and posttranscriptional regulation of methionine adenosyltransferases in liver cancer progression. AB - Down-regulation of the liver-specific MAT1A gene, encoding S-adenosylmethionine (SAM) synthesizing isozymes MATI/III, and up-regulation of widely expressed MAT2A, encoding MATII isozyme, known as MAT1A:MAT2A switch, occurs in hepatocellular carcinoma (HCC). Here we found Mat1A:Mat2A switch and low SAM levels, associated with CpG hypermethylation and histone H4 deacetylation of Mat1A promoter, and prevalent CpG hypomethylation and histone H4 acetylation in Mat2A promoter of fast-growing HCC of F344 rats, genetically susceptible to hepatocarcinogenesis. In HCC of genetically resistant BN rats, very low changes in the Mat1A:Mat2A ratio, CpG methylation, and histone H4 acetylation occurred. The highest MAT1A promoter hypermethylation and MAT2A promoter hypomethylation occurred in human HCC with poorer prognosis. Furthermore, levels of AUF1 protein, which destabilizes MAT1A messenger RNA (mRNA), Mat1A-AUF1 ribonucleoprotein, HuR protein, which stabilizes MAT2A mRNA, and Mat2A-HuR ribonucleoprotein sharply increased in F344 and human HCC, and underwent low/no increase in BN HCC. In human HCC, Mat1A:MAT2A expression and MATI/III:MATII activity ratios correlated negatively with cell proliferation and genomic instability, and positively with apoptosis and DNA methylation. Noticeably, the MATI/III:MATII ratio strongly predicted patient survival length. Forced MAT1A overexpression in HepG2 and HuH7 cells led to a rise in the SAM level, decreased cell proliferation, increased apoptosis, down-regulation of Cyclin D1, E2F1, IKK, NF-kappaB, and antiapoptotic BCL2 and XIAP genes, and up-regulation of BAX and BAK proapoptotic genes. In conclusion, we found for the first time a post-transcriptional regulation of MAT1A and MAT2A by AUF1 and HuR in HCC. Low MATI/III:MATII ratio is a prognostic marker that contributes to determine a phenotype susceptible to HCC and patients' survival. CONCLUSION: Interference with cell cycle progression and I-kappa B kinase (IKK)/nuclear factor kappa B (NF-kappaB) signaling contributes to the antiproliferative and proapoptotic effect of high SAM levels in HCC. PMID- 22318686 TI - Implementation of a smoke-free policy in subsidized multiunit housing: effects on smoking cessation and secondhand smoke exposure. AB - INTRODUCTION: We studied the impact of implementing a comprehensive smoke-free policy in multiunit housing in the Portland, Oregon metropolitan area. Among low income tenants living in a subset of subsidized multiunit buildings, we evaluated cessation-related behaviors, policy knowledge and compliance, and secondhand smoke (SHS) exposure. METHODS: We mailed a self-administered questionnaire to a random sample of 839 current tenants of 17 subsidized buildings 4 months after policy implementation in January 2008 and sent another questionnaire to participants 1 year later. Results are based on 440 tenants who completed both surveys. RESULTS: We observed a self-reported annualized quit rate of 14.7% over the study period (95% CI = 7.9%-21.6%) compared with a historical quit rate in this population of 2.6% (95% CI = 0.6%-4.5%). Almost half of ongoing smokers reduced their cigarette consumption. More smokers correctly reported policy rules for indoor settings than for outdoor settings; self-reported indoor smoking decreased significantly from 59% to 17%. Among nonsmokers, frequent indoor SHS exposure (multiple times per week) decreased significantly from 41% prepolicy to 17% postpolicy. CONCLUSIONS: The implementation of a smoke-free policy was associated with positive changes in cessation-related behaviors and reduced SHS exposure in this population of low-income adults. PMID- 22318687 TI - Hookah use among U.S. college students: results from the National College Health Assessment II. AB - INTRODUCTION: Tobacco use is the leading cause of morbidity and mortality in the United States. Hookah use is a growing tobacco trend among young adults; yet little is known about how young adult college student hookah smokers differ from nonsmokers or cigarette smokers. METHODS: Results from 18- to 24-year-old participants in the Fall 2008-Spring 2009 National College Health Assessment II (N = 82,155) were used in multinomial logistic regression models to compare nonsmokers, cigarette-only smokers, hookah-only smokers, and dual (cigarette and hookah) users. RESULTS: Ten percent of the sample reported hookah use in the last 30 days. Compared with nonsmokers, cigarette, hookah, and dual users were more likely to be younger, male, White, and use other substances (including alcohol). Compared with nonsmokers, hookah and dual users were more likely to be members of fraternities/sororities (odds ratio [OR] = 1.17 and 1.14, respectively), live in the West (OR = 1.49 and 1.31, respectively), and attend larger institutions. Compared with cigarette-only smokers, hookah and dual users were more likely to be younger, male, live on campus, live in the West, attend large institutions, and were less likely to attend public institutions. Compared with cigarette-only smokers, hookah-only users were more likely to be non-White and less likely to use marijuana or other drugs. CONCLUSIONS: Hookah-only and dual users are demographically different than cigarette-only or nonsmoking college students. Interventions for tobacco use on college campuses should address the demographic differences among tobacco users (including polysubstance use) and attempt to recruit students as entering freshman to provide education and prevent hookah use uptake. PMID- 22318688 TI - Reliability of adult self-reported smoking history: data from the tobacco use supplement to the current population survey 2002-2003 cohort. AB - INTRODUCTION: This study examined the reliability of self-reported smoking history measures. The key measures of interest were time since completely quitting smoking among former smokers; age at which fairly regular smoking was initiated among former and current smokers; the number of cigarettes smoked per day and the number of years of daily smoking among former smokers; and never smoking. Another goal was to examine sociodemographic factors and interview method as potential predictors of the odds of strict agreement in responses. METHODS: Data from the 2002-2003 Tobacco Use Supplement to the Current Population Survey were examined. Descriptive analysis was performed to detect discrepant data patterns, and intraclass and Pearson correlations and kappa coefficients were used to assess reporting consistency over the 12-month interval. Multiple logistic regression models with replicate weights were built and fitted to identify factors influencing the logit of agreement for each measure of interest. RESULTS: All measures revealed at least moderate levels of overall agreement. However, upon closer examination, a few measures also showed some considerable differences in absolute value. The highest percentage of these differences was observed for former smokers' reports of the number of years smoking every day. CONCLUSIONS: Overall, the data suggest that self-reported smoking history characteristics are reliable. The logit of agreement over a 12-month period is shown to depend on a few sociodemographic characteristics as well as their interactions with each other and with interview method. PMID- 22318689 TI - Systematic biases in cross-sectional community studies may underestimate the effectiveness of stop-smoking medications. AB - INTRODUCTION: Randomized, controlled trials typically indicate stop-smoking medications (SSMs: e.g., Varenicline, Bupropion, and over-the-counter nicotine replacement therapies) to be effective, whereas cross-sectional community-based studies have found them to be less effective, ineffective, or even associated with higher risk of relapse. Consequently, some critics have suggested SSMs have no useful applications in "real-world" settings. This discrepancy may, however, be due to systematic biases affecting cross-sectional survey outcomes. Namely, failed quit attempts where SSMs were used may be better recalled than failed unassisted attempts. Moreover, smokers who choose to quit using SSMs may be more addicted and thus less likely to succeed. Either of these factors would lead to an over-representation of failed quit attempts among SSM users in cross-sectional surveys even if there were real benefits. METHODS: We report on data from the International Tobacco Control 4-country cohort study to examine the relationship between SSM use, level of nicotine addiction, and the reported date since the start of participants' (N = 1,101) most recent quit attempt. RESULTS: The last quit attempt was reported to have begun longer ago among participants who used SSMs than those who did not. Scores on the Heaviness of Smoking Index, measuring addiction severity, were also higher among SSM users, with no interactions. CONCLUSION: Better recall of quit attempts and stronger addiction to nicotine are two characteristics found more often among smokers using SSMs compared with self quitters, which could potentially bias the assessed effects of SSMs on cessation outcomes in cross-sectional surveys. PMID- 22318690 TI - Specifying evidence-based behavior change techniques to aid smoking cessation in pregnancy. AB - INTRODUCTION: Behavioral support aids smoking cessation in pregnancy. However, it remains unclear which component behavior change techniques (BCTs) contribute to effectiveness or the extent to which these are applied in practice. This study aimed to examine (a) which BCTs were included in effective behavioral support interventions for pregnant smokers (b) the prevalence of use of these BCTs by the English Stop Smoking Services (SSSs). METHODS: From a Cochrane review of smoking cessation behavioral support in pregnancy, 7 interventions were identified as effective in that they increased the odds of cessation by at least 50%, and differences between intervention and control conditions were statistically significant. BCTs in each intervention were identified using an established taxonomy of BCTs. Thirteen treatment manuals from SSSs were coded for inclusion of BCTs. RESULTS: Thirty-seven BCTs were identified across trials of behavioral support for pregnant smokers, with an average of 8 BCTs, and a range of 6-34 BCTs, per intervention. Eleven BCTs were present in at least 2 effective interventions (e.g., facilitate goal setting [n = 6], advise on social support [n = 2], action planning [n = 5], provide rewards contingent on successfully stopping smoking [n = 4]). Only 15.4% of treatment manuals from SSSs contained all 11 BCTs; 53.8% contained at least 6 of them. CONCLUSIONS: While BCTs associated with effective interventions can be identified from systematically reviewed literature, English SSSs appear to use only a limited proportion of these in practice. PMID- 22318691 TI - Rapid smoking may not be aversive in schizophrenia. AB - INTRODUCTION: Aversive smoking has been investigated as a smoking cessation technique that involves rapid smoking in a clinic or laboratory and typically involves (a) puffing every 6-10 s or (b) smoking 3 or more cigarettes sequentially in 8-20 min. Rapid smoking usually results in dizziness, sore throat, nausea, and other unpleasant feelings. METHODS: To explore rapid smoking, 161 smokers (75 with schizophrenia [SS]; 86 controls [CON]) were assessed in a single day (24 +/- 2 hr), ad libitum smoking topography session using the Clinical Research Support System micro portable topography device. RESULTS: SS smoked significantly more cigarettes in the 24-hr period versus CON and the time between puffs, or interpuff interval (IPI) was shorter in SS versus CON by an average of 6.5 s (p < .001). The median IPI was also significantly shorter in SS versus CON (9.3 vs.15.7 s; p < .001). SS were twice as likely to have IPIs <= 6 s than CON (OR = 2.32, 95% CI = 1.68, 3.20; p < .001). SS were also more likely to smoke 3 or more cigarettes in any 20 min during a 24-hr topography session (OR = 2.32, 95% CI = 1.03, 2.44; p < .001). Rapid smoking was associated with baseline characteristics of smoking more cigarettes per day, higher Fagerstrom score, and higher carbon monoxide level but not with serum cotinine values or trans-3' hydroxycotinine/cotinine ratios. CONCLUSIONS: Using either definition, SS exhibit patterns of rapid smoking that they seemingly do not experience as aversive, since it reflects their naturalistic pattern of smoking, outside of the laboratory. PMID- 22318692 TI - Smokeless tobacco marketing and sales practices in Appalachian Ohio following federal regulations. AB - INTRODUCTION: Smokeless tobacco (ST) use is increasingly prevalent among poor and vulnerable groups, especially rural males. Access to tobacco products, as well as marketing messages, is associated with tobacco usage. In June 2010, the Tobacco Control Act (TCA) marked the beginning of federal regulation of the sale and marketing of tobacco products--including ST. The goal of this study was to describe marketing practices over time and to provide early assessment of the federal regulation in rural tobacco-licensed retail outlets. METHODS: Observational data were collected from a sample of retail outlets within three Ohio Appalachian counties. From an estimated 300 retail establishments, a stratified random sample was drawn (n = 86). Trained observers surveyed the sales and marketing of tobacco products. Baseline surveys were conducted between November 2009 and May 2010 before the TCA; follow-up surveys were repeated in August 2010. RESULTS: Follow-up surveys were completed for 79 tobacco-licensed retail outlets. The majority of retail outlets were gas stations or convenience stores. Compared with baseline, there was a significant reduction in the frequency of exterior and interior advertisements observed after the TCA (p < .01). Despite the lack of change in the proportion of stores advertising ST, the number of ST brands being advertised doubled between baseline and follow-up. CONCLUSION: Initial compliance with certain elements of the federal restrictions appears to be high in Appalachian Ohio. The significant increase in ST brands advertised suggests that advertising remains a clear presence in retail outlets in Appalachian Ohio. PMID- 22318693 TI - Adolescent cigarette smokers' and non-cigarette smokers' use of alternative tobacco products. AB - INTRODUCTION: This study uses the most recent data from the nationally representative National Youth Tobacco Survey (NYTS) to examine the use of alternative tobacco products among U.S. cigarette smokers and non-cigarette smokers aged 14-17. Alternative tobacco product use is defined as use of one or more of the following products: smokeless tobacco, cigars, pipes, bidis, or kreteks. METHODS: Using the results from the 2004, 2006, and 2009 NYTS, multivariate logistic regressions were used to investigate separately the extent of alternative tobacco product use in current cigarette smokers and in those who reported not smoking cigarettes controlling for demographic and other independent influences. RESULTS: The results indicate that for adolescent smokers and nonsmokers, the use of one type of alternative tobacco product made it much more likely the individual would use one or more of the other alternative tobacco products. Non-cigarette smokers using these tobacco products appeared to exhibit symptoms of nicotine dependence comparable to those of cigarette smokers. CONCLUSIONS: More information on adolescent use of alternative tobacco products is needed. Current cigarette use declined 3.4% annually over 2004-2009 for the NYTS 14- to 17-year-old population, but this cohort's use of alternative tobacco products was unchanged. The number of adolescents aged 14-17 who did not smoke cigarettes but used alternative tobacco products increased 5.9% per year over the same period. Current surveillance measures need to be expanded in order to gain a more comprehensive understanding of adolescent alternative tobacco use. PMID- 22318694 TI - Is the intergenerational transmission of smoking from mother to child mediated by children's behavior problems? AB - INTRODUCTION: A previous paper used latent class analysis to assign individuals to 1 of 4 adolescent/young adult smoking trajectory classes and then established an association between maternal smoking before, during, and after pregnancy and these classes. In this paper, we examine one possible pathway for this relationship: that maternal smoking during pregnancy may set off a behavioral trajectory which increases the likelihood of problem behaviors generally, of which smoking is one manifestation. METHODS: We used the Behavior Problems Index measure from age 8 through age 12 as a potential mediator. We used a path analysis modeling approach within a multinomial logistic regression (using Mplus) to estimate direct and indirect effects (via behavioral problems) between maternal smoking pattern and child trajectory class. RESULTS: We found small but statistically significant indirect effects via behavioral problems from maternal smoking to child smoking trajectory for membership in all 3 smoking classes, relative to the nonsmoking trajectory, indicating partial mediation. Mediated effects were associated with maternal smoking after pregnancy, no statistically significant mediated effects were found for smoking before or during pregnancy. CONCLUSIONS: The results provided no evidence that the effects of maternal smoking during pregnancy on child smoking trajectory are mediated by problem behavior. Effects from smoking after birth to child smoking trajectory appear to be partially mediated by problem behavior, supporting a behavioral rather than physiological effect of smoking during pregnancy but not ruling out more complex physiological pathways. PMID- 22318695 TI - Tobacco use and suicidality: latent patterns of co-occurrence among black adolescents. AB - INTRODUCTION: Tobacco use is responsible for a considerable portion of the health disparities experienced by Blacks. In addition to its physiological effects, tobacco use has consistently been shown to be associated with suicidality among adolescents. The purpose of the present study is to describe the association between specific patterns of tobacco use behavior and those of suicidality among a nationally representative sample of Black high school students. METHODS: Responses from Black adolescents (N = 2,931) who completed the 2007 Youth Risk Behavior Surveillance Survey were included. Latent class analysis was utilized to identify typologies based on two domains: (a) lifetime and recent tobacco use and (b) suicidality. The association between tobacco use class membership and suicidality class membership as well as the direct effects of age and gender on class membership was also investigated. RESULTS: A significant proportion of Black youth reported smoking and suicidal behaviors. A 4-class model provided the best overall fit to the data for tobacco use behavior (nonsmokers, former smokers, light current smokers, and frequent current smokers); a 3-class model provided the best overall fit to the data for suicidality (not suicidal, mild suicidality, suicidal). Smoking status was associated with suicidality class membership, with more intense patterns of smoking related to increased probability of identification with both mild suicidality and being classified as suicidal compared with not suicidal. CONCLUSIONS: The results of this study indicate that any current smoking status increases the likelihood of suicidality at least 5-fold and provides incentive to target this specific portion of the population of Black adolescent smokers. PMID- 22318696 TI - Qualitative detection of desmopressin in plasma by liquid chromatography-tandem mass spectrometry. AB - This work describes a liquid chromatography-electrospray tandem mass spectrometry method for detection of desmopressin in human plasma in the low femtomolar range. Desmopressin is a synthetic analogue of the antidiuretic hormone arginine vasopressin and it might be used by athletes as a masking agent in the framework of blood passport controls. Therefore, it was recently added by the World Anti Doping Agency to the list of prohibited substances in sport as a masking agent. Mass spectrometry characterization of desmopressin was performed with a high resolution Orbitrap-based mass spectrometer. Detection of the peptide in the biological matrix was achieved using a triple-quadrupole instrument with an electrospray ionization interface after protein precipitation, weak cation solid phase extraction and high performance liquid chromatography separation with an octadecyl reverse-phase column. Identification of desmopressin was performed using three product ions, m/z 328.0, m/z 120.0, and m/z 214.0, from the parent ion, m/z 535.5. The extraction efficiency of the method at the limit of detection was estimated as 40% (n = 10), the ion suppression as 5% (n = 10), and the limit of detection was 50 pg/ml (signal-to-noise ratio greater than 3). The selectivity of the method was verified against several endogenous and synthetic desmopressin related peptides. The performance and the applicability of the method were tested by analysis of clinical samples after administration of desmopressin via intravenous, oral, and intranasal routes. Only after intravenous administration could desmopressin be successfully detected. PMID- 22318697 TI - Analytical methods for determination of new fluoroquinolones in biological matrices and pharmaceutical formulations by liquid chromatography: a review. AB - Fluoroquinolones are one of the most promising and intensively studied drugs of contemporary anti-infective chemotherapy. New fluoroquinolone antibacterials with improved pharmacokinetic properties and a broad spectrum of activity have been developed, opening new windows of opportunity for clinical use. To our knowledge, no comprehensive and critical review of the analytical methods for the determination of these agents, which correspond to the third- and fourth generation quinolones, has yet been published. This work summarizes for the first time most of the liquid chromatographic methods reported in the literature for the separation and quantification of the new fluoroquinolones in biological matrices and pharmaceutical formulations. A systematic and detailed survey of physicochemical properties, sample preparation procedures, and chromatographic and detection conditions is presented herein. In the course of this review several liquid chromatographic methods are discussed: reversed-phase high performance liquid chromatography (RP-HPLC), ion-exchange high-performance liquid chromatography (IEX-HPLC), hydrophilic interaction liquid chromatography (HILIC), high-performance thin-layer chromatography (HPTLC) and other chiral chromatographic methods. Their advantages, applicability and limitations are also examined. PMID- 22318698 TI - Separation and quantitative determination of 6alpha-hydroxycortisol and 6beta hydroxycortisol in human urine by high-performance liquid chromatography with ultraviolet absorption detection. AB - The present study developed an high-performance liquid chromatography (HPLC) method for the simultaneous determination of urinary metabolites of endogenous cortisol, 6alpha-hydroxycortisol (6alpha-OHF) and 6beta-hydroxycortisol (6beta OHF), in human urine, using 6alpha-hydroxycorticosterone as internal standard. 6alpha-OHF and 6beta-OHF were extracted from urine with ethyl acetate by using a Sep-Pak C(18) plus cartridge. Separation of the stereoisomers was achieved on a reversed-phase hybrid column by a gradient elution of (A) 0.05 M KH(2)PO(4)-0.01 M CH(3)COOH (pH 3.77) and (B) 0.05 M KH(2)PO(4)-0.01 M CH(3)COOH/acetonitrile (2:3, v/v). 6alpha-OHF and 6beta-OHF were well separated on an XTerra MS C(18) 5 MUm column using two types of stepwise gradient elution program (programs 2 and 3). Resolutions of 6alpha-OHF and 6beta-OHF were Rs = 4.41 for program 2 and Rs = 4.60 for program 3. The analysis was performed within 23~26 min, monitored by UV absorbance at 239 nm. The lower limits of detection of 6alpha-OHF and 6beta-OHF were 0.80 ng per injection (s/n = ca. 8), and the lower limits of quantification were 5.02 ng/ml for 6alpha-OHF and 41.08 ng/ml for 6beta-OHF, respectively. The within-day reproducibilities in the amounts of 6alpha-OHF and 6beta-OHF determined were in good agreement with the actual amounts added, the relative errors being -5.37% and -3.73% (gradient 2) and -5.69% and -3.96% (gradient 3) for both 6alpha-OHF and 6beta-OHF, respectively. The inter-assay precisions (RSDs) for 6alpha-OHF and 6beta-OHF were less than 1.99% (gradient 2) and 2.61% (gradient 3), respectively. The present HPLC method was applied to the measurement of 6alpha-OHF and 6beta-OHF in urine to evaluate the time courses of 6alpha-hydroxylation and 6beta-hydroxylation clearances of cortisol during 40 days for phenotyping CYP3A in a healthy subject. PMID- 22318699 TI - Chemometric approach for development, optimization, and validation of different chromatographic methods for separation of opium alkaloids. AB - The excessive and continuously growing interest in the simultaneous determination of poppy alkaloids imposes the development and optimization of convenient high throughput methods for the assessment of the qualitative and quantitative profile of alkaloids in poppy straw. Systematic optimization of two chromatographic methods (gas chromatography (GC)/flame ionization detector (FID)/mass spectrometry (MS) and reversed-phase (RP)-high-performance liquid chromatography (HPLC)/diode array detector (DAD)) for the separation of alkaloids from Papaver somniferum L. (Papaveraceae) was carried out. The effects of various conditions on the predefined chromatographic descriptors were investigated using chemometrics. A full factorial linear design of experiments for determining the relationship between chromatographic conditions and the retention behavior of the analytes was used. Central composite circumscribed design was utilized for the final method optimization. By conducting the optimization of the methods in very rational manner, a great deal of excessive and unproductive laboratory research work was avoided. The developed chromatographic methods were validated and compared in line with the resolving power, sensitivity, accuracy, speed, cost, ecological aspects, and compatibility with the poppy straw extraction procedure. The separation of the opium alkaloids using the GC/FID/MS method was achieved within 10 min, avoiding any derivatization step. This method has a stronger resolving power, shorter analysis time, better cost/effectiveness factor than the RP-HPLC/DAD method and is in line with the "green trend" of the analysis. The RP HPLC/DAD method on the other hand displayed better sensitivity for all tested alkaloids. The proposed methods provide both fast screening and an accurate content assessment of the six alkaloids in the poppy samples obtained from the selection program of Papaver strains. PMID- 22318700 TI - A contribution to the lichenized fungi of Bosnia and Herzegovina. AB - A list of 27 species of lichenized fungi from Bosnia and Herzegovina is presented, based on herbarium specimens kept in GZU. Six species are new to Bosnia and Herzegovina: Fuscopannaria sampaiana, Lecidea tessellata, Micarea melaena, Rinodina polysporoides, Usnea barbata, and Xanthoparmelia verruculifera. PMID- 22318701 TI - A facile route to flavone and neoflavone backbones via a regioselective palladium catalyzed oxidative Heck reaction. AB - A straightforward and atom-economical base-free palladium-catalyzed regioselective direct arylation of coumarins and chromenones is devised. This protocol is compatible with a wide variety of electron-donating and -withdrawing substituents and allows construction of various biologically important flavone and neoflavone backbones. PMID- 22318702 TI - Effects of vitamins, probiotics, and protein level on semen traits and some seminal plasma macro- and microminerals of male broiler breeders after zinc induced molting. AB - This study was conducted to investigate the effects of vitamin E, vitamin C, probiotics, dietary protein level, and their combination on semen traits and seminal plasma macro- and microminerals in 65-week-old male broiler breeders after zinc-induced molting. One hundred eighty birds were induced to molt by mixing zinc oxide (3,000 mg/kg) in the diet. The birds were divided into six groups (five replicates) by completely randomized design. One group was kept as control (16% CP), while the other five were supplemented with vitamin E (100 IU/kg feed), vitamin C (500 IU/kg feed) probiotics (50 mg/L), protein level (14% CP), and their combination. Semen samples were weekly collected for determination of semen volume, sperm concentration, motility, and dead sperm percentage. Analyses of Na, K, Ca and Mg, Zn, Fe, Mn, and Cu in seminal plasma were also performed. Overall, mean semen volume was significantly high in vitamin E and C supplemented groups compared to control. Overall mean sperm motility was significantly higher in vitamin E supplemented group, whereas dead sperm percentage was significantly lower in the vitamin C group compared to control. Mineral analyses revealed that overall mean seminal plasma Mg increased significantly in vitamin E and C supplemented groups compared to control. Similarly, significantly high overall mean seminal plasma Cu concentration was observed in vitamins E and C and combination groups. It can be concluded that vitamins have a vital role in improving semen quality and bioavailability of Mg and Cu in seminal plasma of the post-molt cockerels. PMID- 22318703 TI - Regulation of microRNA biogenesis and function. AB - MicroRNAs (miRNAs) are considered as key regulators of literally all cellular pathways. Therefore, miRNA biosynthesis and their individual cellular functions must be tightly regulated as well. MiRNAs are transcribed as primary transcripts, which are processed to mature miRNAs in two consecutive maturation steps. Finally, the mature miRNA is incorporated into a miRNA-protein complex, where it directly interacts with a member of the Argonaute (Ago) protein family. The miRNA guides such protein complexes to partial complementary target sites, which are typically located in the 3' untranslated region (UTR) of mRNAs leading to inhibition of gene expression. MiRNA activity and abundance is regulated on various levels ranging from transcription and processing to target site binding and miRNA stability. Recent advances in our understanding of how miRNA activity is regulated in mammalian cells are summarised and discussed in this review article. PMID- 22318704 TI - Fine structural organization of the hemiellipsoid body of the land hermit crab, Coenobita clypeatus. AB - Electron microscopical observations of the hemiellipsoid bodies of the land hermit crab Coenobita clypeatus resolve microglomerular synaptic complexes that are comparable to those observed in the calyces of insect mushroom bodies and which characterize olfactory inputs onto intrinsic neurons. In an adult hermit crab, intrinsic neurons and one class of efferent neurons originate from neuronal somata of globuli cells covering the hemiellipsoid bodies. Counts of their nucleoli show that about 120,000 globuli cells supply each hemiellipsoid body in an adult hermit crab. This number is comparable to the number of globuli cells supplying mushroom bodies of certain insects, such as honey bees and cockroaches. Counts of axons in tracts leading from the olfactory lobes to the hemiellipsoid bodies resolve 20,000 afferent axons, however, an order of magnitude greater than known for any insect. These afferent axons provide numerous swollen varicosities, each presynaptic to many small profiles, and thus comparable to the microglomeruli that characterize insect mushroom body calyces. Also, common to mushroom bodies and hemiellipsoid bodies are arrangements of intrinsic neurons, afferent neurons containing dense core vesicles, and systems of serial synaptic complexes that relate to postsynaptic profiles of efferent neurons. Together, the ultrastructural organization of the hemiellipsoid bodies of C. clypeatus supports the proposition that this center may share a common origin with the insect mushroom body despite obvious divergent evolution of overall shape. PMID- 22318705 TI - Digital image analysis of radial shrinkage of fresh spruce (Picea abies L.) wood. AB - Contact-free digital image analysis was performed of the radial shrinkage of fresh, fully saturated small spruce wood beams. An experimental test set-up was developed to ensure constant distance from the charge-coupled device camera to the sample surface as well as constant climate and light conditions during the whole experiment. Dimensional changes were observed immediately after the drying process began. An unexpected distinct effect could be observed which could not be explained by drying surface layers only. After a fast initial radial shrinkage a slowing down of the dimensional changes occurred at high mean moisture contents. A complete interruption of any dimensional changes followed. Finally, a recovery from shrinkage was even observed. It is assumed that strong negative pressure occurred in the fully saturated capillaries owing to dehydration which led to additional dimensional changes. As a consequence, the break of the water column and aeration in these capillaries finally resulted in a recovery period in the shrinkage rate due to the pressure release. After this effect, the dehydration was characterized by a phase of fast and almost linear shrinkage due to drying surface layers. Finally, the shrinkage slowed down to zero when reaching equilibrium moisture content. PMID- 22318706 TI - Erythropoietin-induced progenitor cell mobilisation in patients with acute ST segment-elevation myocardial infarction and restenosis. AB - Erythropoietin improves myocardial function and enhances re-endothelialisation. Aim of this study was to analyse progenitor cell mobilisation and restenosis in patients from the Regeneration of Vital Myocardium in ST-Segment Elevation Myocardial Infarction by Erythropoietin (REVIVAL-3) study. Patients with STEMI undergoing percutaneous coronary intervention (PCI) were randomly assigned to Epoetin beta (EPO) (n=68) or placebo (n=70). Drug-eluting stents (DES) were utilised in 93% of patients receiving EPO and in 95% of patients receiving placebo (p=0.83). Serial venous blood samples were drawn; CD133+ progenitor cells were quantified by four-colour flow cytometry and cytokines interleukin (IL) 1beta, IL-6, IL-8, IL-10, IL-12 and tumour necrosis factor (TNF) alpha were analysed by cytometric bead array. Forty-eight hours after PCI a significant increase in CD133+ progenitor cells was observed in the EPO group. Yet, no differences in plasma cytokines were found. Quantitative coronary angiography after six months revealed an increase in segment diameter stenosis in the EPO group (32 +/- 19% vs. 26 +/- 14%, p=0.046). However, this increase in neointima generation was not associated with progenitor cell mobilisation. EPO in patients with STEMI treated with PCI is associated with an increase in diameter stenosis that is not associated with circulating progenitor cells. PMID- 22318711 TI - Evaluation of participant satisfaction with community therapy: a mental health strategy in primary care. AB - Actions aimed at health promotion and disease prevention must prioritize the entry point to the health system. In this sense, it is proposed that Community Therapy (CT) be inserted as a mental health care tool in Primary Care. The purpose of this study is to assess user satisfaction with CT in Primary Care. It is assessment, cross-sectional study with a representative sample of users of CT services in Primary Care in the municipality of Joao Pessoa, Paraiba, Brazil. Of the 198 interviewees, 165 (83.3%) of the sample reported that they were always respected, evidenced by aspects of respect and dignity; 109 (55.1%) individuals stated they were listened to, revealing internal consistency of 0.7187, and in turn, exhibiting the true validity of the user satisfaction construct with respect to CT. Thus, users displayed positive satisfaction, reflected by respect, dignity, receptiveness, resolution, listening and comprehension received at CT, where empathy is exhibited and mental suffering is relieved. Moreover, CT is an important mental health tool in primary care. PMID- 22318712 TI - Risk of anastomotic leakage with non-steroidal anti-inflammatory drugs in colorectal surgery. AB - BACKGROUND: With the implementation of multimodal analgesia regimens in fast track surgery programmes, non-steroidal anti-inflammatory drugs (NSAIDs) are being prescribed routinely. However, doubts have been raised concerning the safety of NSAIDs in terms of anastomotic healing. METHODS: Data on patients who had undergone primary colorectal anastomosis at two teaching hospitals between January 2008 and December 2010 were analysed retrospectively. Exact use of NSAIDs was recorded. Rates of anastomotic leakage were compared between groups and corrected for known risk factors in both univariable and multivariable analyses. RESULTS: A total of 795 patients were divided into four groups according to NSAID use: no NSAIDs (471 patients), use of non-selective NSAIDs (201), use of selective cyclo-oxygenase (COX) 2 inhibitors (79), and use of both selective and non-selective NSAIDs (44). The overall leak rate was 9.9 per cent (10.0 per cent for right colonic, 8.7 per cent for left colonic and 12.4 per cent for rectal anastomoses). Known risk factors such as smoking and use of steroids were not significantly associated with anastomotic leakage. Stapled anastomosis was identified as an independent predictor of leakage in multivariable analysis (odds ratio (OR) 2.22, 95 per cent confidence interval 1.30 to 3.80; P = 0.003). Patients on NSAIDs had higher anastomotic leakage rates than those not on NSAIDs (13.2 versus 7.6 per cent; OR 1.84, 1.13 to 2.98; P = 0.010). This effect was mainly due to non-selective NSAIDs (14.5 per cent; OR 2.13, 1.24 to 3.65; P = 0.006), not selective COX-2 inhibitors (9 per cent; OR 1.16, 0.49 to 2.75; P = 0.741). The overall mortality rate was 4.2 per cent, with no significant difference between groups (P = 0.438). CONCLUSION: Non-selective NSAIDs may be associated with anastomotic leakage. PMID- 22318713 TI - Ab initio and density functional theoretical design and screening of model crown ether based ligand (host) for extraction of lithium metal ion (guest): effect of donor and electronic induction. AB - The structures, energetic and thermodynamic parameters of model crown ethers with different donor, cavity and electron donating/ withdrawing functional group have been determined with ab initio MP2 and density functional theory in gas and solvent phase. The calculated values of binding energy/ enthalpy for lithium ion complexation are marginally higher for hard donor based aza and oxa crown compared to soft donor based thia and phospha crown. The calculated values of binding enthalpy for lithium metal ion with 12C4 at MP2 level of theory is in good agreement with the available experimental result. The binding energy is altered due to the inductive effect imparted by the electron donating/ withdrawing group in crown ether, which is well correlated with the values of electron transfer. The role of entropy for extraction of hydrated lithium metal ion by different donor and functional group based ligand has been demonstrated. The HOMO-LUMO gap is decreased and dipole moment of the ligand is increased from gas phase to organic phase because of the dielectric constant of the solvent. The gas phase binding energy is reduced in solvent phase as the solvent molecules weaken the metal-ligand binding. The theoretical values of extraction energy for LiCl salt from aqueous solution in different organic solvent is validated by the experimental trend. The study presented here should contribute to the design of model host ligand and screening of solvent for metal ion recognition and thus can contribute in planning the experiments. PMID- 22318714 TI - Ascorbate antagonizes nickel ion to regulate JMJD1A expression in kidney cancer cells. AB - Abnormal expression of histone demethylase Jumonji domain-containing protein 1A (JMJD1A) is associated with many kinds of cancers. JMJD1A is also a hypoxic response gene and its expression is regulated by hypoxia-inducible factor-1alpha (HIF-1alpha). In this study, we determined the role of JMJD1A in development and hypoxia pathway. We also measured the expression of JMJD1A and two hypoxia factors glucose transporter 1 (GLUT1) and vascular endothelial growth factor (VEGF) in 786-0 and HEK293 cells treated with different concentrations of NiCl(2) (2.5-100 MUM) for 24 h, and found that JMJD1A mRNA and protein were up-regulated with increased concentrations of NiCl(2). We then observed that ascorbate could retard the up-regulated effect of NiCl(2)-induced JMJD1A expression in a dose dependent manner through decreasing the stability of HIF-1alpha protein. Immunohistochemical analysis further demonstrated ascorbate antagonized Ni(2+) induced up-regulation of JMJD1A expression in 786-0, HEK293, and OS-RC-2 cells. These findings suggest that both Ni(2+) and ascorbate can regulate the expression of histone demethylase JMJD1A, which is important for cancer development or inhibition. PMID- 22318715 TI - Enhanced learning and memory in GAT1 heterozygous mice. AB - gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. The termination of GABA transmission is through the action of a family of membrane proteins, called GABA transporters (GAT1-4). It is well established that GABA system is involved in the modulation of memory. Our previous study showed that homozygous GAT1(-/-) mice exhibited impaired hippocampus-dependent learning and memory. To evaluate the impact of endogenous reduced GABA reuptake on mice cognitive behaviors, the ability of learning and memory of heterozygous GAT1(+/-) mice was detected by the passive avoidance paradigm and Morris water maze. The hole board paradigm was also used to measure changes in anxiety-related behavior or exploratory behavior in such mice. As one form of synaptic plasticity, long-term potentiation was recorded in the mouse hippocampal CA1 area. We found that GAT1(+/-) mice displayed increased learning and memory, decreased anxiety-like behaviors, and highest synaptic plasticity compared with wild-type and homozygous GAT1(-/-) mice. Our results suggest that a moderate reduction in GAT1 activity causes the enhancement of learning and memory in mice. PMID- 22318716 TI - Structure insights into mechanisms of ATP hydrolysis and the activation of human heat-shock protein 90. AB - The activation of molecular chaperone heat-shock protein 90 (Hsp90) is dependent on ATP binding and hydrolysis, which occurs in the N-terminal domains of protein. Here, we have determined three crystal structures of the N-terminal domain of human Hsp90 in native and in complex with ATP and ATP analog, providing a clear view of the catalytic mechanism of ATP hydrolysis by Hsp90. Additionally, the binding of ATP leads the N-terminal domains to be an intermediate state that could be used to partially explain why the isolated N-terminal domain of Hsp90 has very weak ATP hydrolytic activity. PMID- 22318717 TI - Hepatic androgen receptor suppresses hepatocellular carcinoma metastasis through modulation of cell migration and anoikis. AB - Early reports suggested androgen/androgen receptor (AR) signals promote hepatocarcinogenesis. However, all antiandrogen clinical trials failed in advanced hepatocellular carcinoma (HCC) without reasonable explanations. We examined AR functions in HCC cancer metastasis in this study. We examined hepatic AR roles in HCC metastasis by comparing liver hepatocyte AR knockout and wildtype in a carcinogen-induced HCC mouse model. We examined tumor histology, cancer metastatic risks, and cancer survival in vivo, as well as cell anoikis and migration using primary hepatic tumor culture in vitro. We also examined therapeutic potentials of AR expression combined with the molecular targeting agent sorafenib in an HCC metastasis mouse model. We found a novel cancer phenotype in which mice lacking hepatic AR developed more undifferentiated tumors and larger tumor size at the metastatic stage. These mice also died earlier with increased lung metastasis, suggesting that hepatic AR may play dual yet opposite roles to promote HCC initiation but suppress HCC metastasis. Mechanistic dissection found that hepatic AR could enhance anoikis and suppress migration of HCC cells by way of suppression of p38 phosphorylation/activation and the nuclear factor kappa B (NF-kappaB)/matrix metallopeptidase 9 (MMP9) pathway, respectively. In addition, the in vivo preclinical trials concluded that a combination therapy of increased AR expression and reduced multiple-kinase inhibitor (sorafenib) exhibited better therapeutic efficacy. CONCLUSION: Our study demonstrates that AR could orchestrate intrahepatic signaling hierarchies and cellular behaviors, consequently affect HCC progression. Results from combination therapy shed light on developing new therapeutic paradigms for battling HCC at later metastatic stages. PMID- 22318718 TI - Proteomics shows new faces for the old penicillin producer Penicillium chrysogenum. AB - Fungi comprise a vast group of microorganisms including the Ascomycota (majority of all described fungi), the Basidiomycota (mushrooms or higher fungi), and the Zygomycota and Chytridiomycota (basal or lower fungi) that produce industrially interesting secondary metabolites, such as beta-lactam antibiotics. These compounds are one of the most commonly prescribed drugs world-wide. Since Fleming's initial discovery of Penicillium notatum 80 years ago, the role of Penicillium as an antimicrobial source became patent. After the isolation of Penicillium chrysogenum NRRL 1951 six decades ago, classical mutagenesis and screening programs led to the development of industrial strains with increased productivity (at least three orders of magnitude). The new "omics" era has provided the key to understand the underlying mechanisms of the industrial strain improvement process. The review of different proteomics methods applied to P. chrysogenum has revealed that industrial modification of this microorganism was a consequence of a careful rebalancing of several metabolic pathways. In addition, the secretome analysis of P. chrysogenum has opened the door to new industrial applications for this versatile filamentous fungus. PMID- 22318719 TI - Crystallography, evolution, and the structure of viruses. AB - My undergraduate education in mathematics and physics was a good grounding for graduate studies in crystallographic studies of small organic molecules. As a postdoctoral fellow in Minnesota, I learned how to program an early electronic computer for crystallographic calculations. I then joined Max Perutz, excited to use my skills in the determination of the first protein structures. The results were even more fascinating than the development of techniques and provided inspiration for starting my own laboratory at Purdue University. My first studies on dehydrogenases established the conservation of nucleotide-binding structures. Having thus established myself as an independent scientist, I could start on my most cherished ambition of studying the structure of viruses. About a decade later, my laboratory had produced the structure of a small RNA plant virus and then, in another six years, the first structure of a human common cold virus. Many more virus structures followed, but soon it became essential to supplement crystallography with electron microscopy to investigate viral assembly, viral infection of cells, and neutralization of viruses by antibodies. A major guide in all these studies was the discovery of evolution at the molecular level. The conservation of three-dimensional structure has been a recurring theme, from my experiences with Max Perutz in the study of hemoglobin to the recognition of the conserved nucleotide-binding fold and to the recognition of the jelly roll fold in the capsid protein of a large variety of viruses. PMID- 22318720 TI - Cdc73 subunit of Paf1 complex contains C-terminal Ras-like domain that promotes association of Paf1 complex with chromatin. AB - The conserved Paf1 complex localizes to the coding regions of genes and facilitates multiple processes during transcription elongation, including the regulation of histone modifications. However, the mechanisms that govern Paf1 complex recruitment to active genes are undefined. Here we describe a previously unrecognized domain within the Cdc73 subunit of the Paf1 complex, the Cdc73 C domain, and demonstrate its importance for Paf1 complex occupancy on transcribed chromatin. Deletion of the C-domain causes phenotypes associated with elongation defects without an apparent loss of complex integrity. Simultaneous mutation of the C-domain and another subunit of the Paf1 complex, Rtf1, causes enhanced mutant phenotypes and loss of histone H3 lysine 36 trimethylation. The crystal structure of the C-domain reveals unexpected similarity to the Ras family of small GTPases. Instead of a deep nucleotide-binding pocket, the C-domain contains a large but comparatively flat surface of highly conserved residues, devoid of ligand. Deletion of the C-domain results in reduced chromatin association for multiple Paf1 complex subunits. We conclude that the Cdc73 C-domain probably constitutes a protein interaction surface that functions with Rtf1 in coupling the Paf1 complex to the RNA polymerase II elongation machinery. PMID- 22318721 TI - Peptidyl-prolyl isomerase Pin1 controls down-regulation of conventional protein kinase C isozymes. AB - The down-regulation or cellular depletion of protein kinase C (PKC) attendant to prolonged activation by phorbol esters is a widely described property of this key family of signaling enzymes. However, neither the mechanism of down-regulation nor whether this mechanism occurs following stimulation by physiological agonists is known. Here we show that the peptidyl-prolyl isomerase Pin1 provides a timer for the lifetime of conventional PKC isozymes, converting the enzymes into a species that can be dephosphorylated and ubiquitinated following activation induced by either phorbol esters or natural agonists. The regulation by Pin1 requires both the catalytic activity of the isomerase and the presence of a Pro immediately following the phosphorylated Thr of the turn motif phosphorylation site, one of two C-terminal sites that is phosphorylated during the maturation of PKC isozymes. Furthermore, the second C-terminal phosphorylation site, the hydrophobic motif, docks Pin1 to PKC. Our data are consistent with a model in which Pin1 binds the hydrophobic motif of conventional PKC isozymes to catalyze the isomerization of the phospho-Thr-Pro peptide bond at the turn motif, thus converting these PKC isozymes into species that can be efficiently down-regulated following activation. PMID- 22318722 TI - Rpn1 and Rpn2 coordinate ubiquitin processing factors at proteasome. AB - Substrates tagged with (poly)ubiquitin for degradation can be targeted directly to the 26 S proteasome where they are proteolyzed. Independently, ubiquitin conjugates may also be delivered by bivalent shuttles. The majority of shuttles attach to the proteasome through a ubiquitin-like domain (UBL) while anchoring cargo at a C-terminal polyubiquitin-binding domain(s). We found that two shuttles of this class, Rad23 and Dsk2, dock at two different receptor sites embedded within a single subunit of the 19 S proteasome regulatory particle, Rpn1. Their association/dissociation constants and affinities for Rpn1 are similar. In contrast, another UBL-containing protein, the deubiquitinase Ubp6, is also anchored by Rpn1, yet it dissociates slower, thus behaving as an occasional proteasome subunit that is distinct from the transiently associated shuttles. Two neighboring subunits, Rpn10 and Rpn13, show a marked preference for polyubiquitin over UBLs. Rpn10 attaches to the central solenoid portion of Rpn1, although this association is stabilized by the presence of a third subunit, Rpn2. Rpn13 binds directly to Rpn2. These intrinsic polyubiquitin receptors may compete with substrate shuttles for their polyubiquitin-conjugate cargos, thereby aiding release of the emptied shuttles. By binding multiple ubiquitin-processing factors simultaneously, Rpn1 is uniquely suited to coordinate substrate recruitment, deubiquitination, and movement toward the catalytic core. The broad range of affinities for ubiquitin, ubiquitin-like, and non-ubiquitin signals by adjacent yet nonoverlapping sites all within the base represents a hub of activity that coordinates the intricate relay of substrates within the proteasome, and consequently it influences substrate residency time and commitment to degradation. PMID- 22318723 TI - Amino acid templating mechanisms in selection of nucleotides opposite abasic sites by a family a DNA polymerase. AB - Cleavage of the N-glycosidic bond that connects the nucleobase to the backbone in DNA leads to abasic sites, the most frequent lesion under physiological conditions. Several DNA polymerases preferentially incorporate an A opposite this lesion, a phenomenon termed "A-rule." Accordingly, KlenTaq, the large fragment of Thermus aquaticus DNA polymerase I, incorporates a nucleotide opposite an abasic site with efficiencies of A > G > T > C. Here we provide structural insights into constraints of the active site during nucleotide selection opposite an abasic site. It appears that these confines govern the nucleotide selection mainly by interaction of the incoming nucleotide with Tyr-671. Depending on the nucleobase, the nucleotides are differently positioned opposite Tyr-671 resulting in different alignments of the functional groups that are required for bond formation. The distances between the alpha-phosphate and the 3'-primer terminus increases in the order A < G < T, which follows the order of incorporation efficiency. Additionally, a binary KlenTaq structure bound to DNA containing an abasic site indicates that binding of the nucleotide triggers a remarkable rearrangement of enzyme and DNA template. The ability to resolve the stacking arrangement might be dependent on the intrinsic properties of the respective nucleotide contributing to nucleotide selection. Furthermore, we studied the incorporation of a non-natural nucleotide opposite an abasic site. The nucleotide was often used in studying stacking effects in DNA polymerization. Here, no interaction with Tyr-761 as found for the natural nucleotides is observed, indicating a different reaction path for this non-natural nucleotide. PMID- 22318724 TI - Structural basis for selective vascular endothelial growth factor-A (VEGF-A) binding to neuropilin-1. AB - Neuropilin-1 (Nrp1) is an essential receptor for angiogenesis that binds to VEGF A. Nrp1 binds directly to VEGF-A with high affinity, but the nature of their selective binding has remained unclear. Nrp1 was initially reported to bind to the exon 7-encoded region of VEGF-A and function as an isoform-specific receptor for VEGF-A(164/165). Recent data have implicated exon 8-encoded residues, which are found in all proangiogenic VEGF-A isoforms, in Nrp binding. We have determined the crystal structure of the exon 7/8-encoded VEGF-A heparin binding domain in complex with the Nrp1-b1 domain. This structure clearly demonstrates that residues from both exons 7 and 8 physically contribute to Nrp1 binding. Using an in vitro binding assay, we have determined the relative contributions of exon 7- and 8-encoded residues. We demonstrate that the exon 8-encoded C-terminal arginine is essential for the interaction of VEGF-A with Nrp1 and mediates high affinity Nrp binding. Exon 7-encoded electronegative residues make additional interactions with the L1 loop of Nrp1. Although otherwise conserved, the primary sequences of Nrp1 and Nrp2 differ significantly in this region. We further show that VEGF-A(164) binds 50-fold more strongly to Nrp1 than Nrp2. Direct repulsion between the electronegative exon 7-encoded residues of the heparin binding domain and the electronegative L1 loop found only in Nrp2 is found to significantly contribute to the observed selectivity. The results reveal the basis for the potent and selective binding of VEGF-A(164) to Nrp1. PMID- 22318725 TI - Ubiquitin- and MDM2 E3 ligase-independent proteasomal turnover of nucleostemin in response to GTP depletion. AB - Nucleostemin (NS) is a nucleolar GTP-binding protein essential for ribosomal biogenesis, proliferation, and animal embryogenesis. It remains largely unclear how this protein is regulated. While working on its role in suppression of MDM2 and activation of p53, we observed that NS protein (but not mRNA) levels decreased drastically in response to GTP depletion. When trying to further elucidate the molecular mechanism(s) underlying this unusual phenomenon, we found that NS was degraded independently of ubiquitin and MDM2 upon GTP depletion. First, depletion of GTP by treating cells with mycophenolic acid decreased the level of NS without apparently affecting the levels of other nucleolar proteins. Second, mutant NS defective in GTP binding and exported to the nucleoplasm was much less stable than wild-type NS. Although NS was ubiquitinated in cells, its polyubiquitination was independent of Lys-48 or Lys-63 in the ubiquitin molecule. Inactivation of E1 in E1 temperature-sensitive mouse embryonic fibroblast (MEF) cells failed to prevent the proteasomal degradation of NS. The proteasomal turnover of NS was also MDM2-independent, as its half-life in p53/MDM2 double knock-out MEF cells was the same as that in wild-type MEF cells. Moreover, NS ubiquitination was MDM2-independent. Mycophenolic acid or doxorubicin induced NS degradation in various human cancerous cells regardless of the status of MDM2. Hence, these results indicate that NS undergoes a ubiquitin- and MDM2-independent proteasomal degradation when intracellular GTP levels are markedly reduced and also suggest that ubiquitination of NS may be involved in regulation of its function rather than stability. PMID- 22318726 TI - Insulin and insulin-like growth factor II differentially regulate endocytic sorting and stability of insulin receptor isoform A. AB - The insulin receptor isoform A (IR-A) binds both insulin and insulin-like growth factor (IGF)-II, although the affinity for IGF-II is 3-10-fold lower than insulin depending on a cell and tissue context. Notably, in mouse embryonic fibroblasts lacking the IGF-IR and expressing solely the IR-A (R-/IR-A), IGF-II is a more potent mitogen than insulin. As receptor endocytosis and degradation provide spatial and temporal regulation of signaling events, we hypothesized that insulin and IGF-II could affect IR-A biological responses by differentially regulating IR A trafficking. Using R-/IR-A cells, we discovered that insulin evoked significant IR-A internalization, a process modestly affected by IGF-II. However, the differential internalization was not due to IR-A ubiquitination. Notably, prolonged stimulation of R-/IR-A cells with insulin, but not with IGF-II, targeted the receptor to a degradative pathway. Similarly, the docking protein insulin receptor substrate 1 (IRS-1) was down-regulated after prolonged insulin but not IGF-II exposure. Similar results were also obtained in experiments using [NMeTyr(B26)]-insulin, an insulin analog with IR-A binding affinity similar to IGF-II. Finally, we discovered that IR-A was internalized through clathrin dependent and -independent pathways, which differentially regulated the activation of downstream effectors. Collectively, our results suggest that a lower affinity of IGF-II for the IR-A promotes lower IR-A phosphorylation and activation of early downstream effectors vis a vis insulin but may protect IR-A and IRS-1 from down-regulation thereby evoking sustained and robust mitogenic stimuli. PMID- 22318727 TI - Role of basic science in the development of new medicines: examples from the eicosanoid field. AB - The role of basic science in the development of health care has received more and more attention. In my own area of research involving the so-called eicosanoids, there are many examples of how studies of structure and function of small molecules, as well as proteins and genes, have led to new therapeutic agents for treatment of a variety of diseases. In most of the cases, the discoveries have resulted in the recognition of novel therapeutic targets amenable to modulation by small molecules. However, there are also examples in which the molecular mechanisms of actions of drugs, discovered by phenotypic screening, have been elucidated. The majority of the examples in this article consist of approved drugs; however, in some cases, ongoing developments of potential therapeutics are cited. PMID- 22318728 TI - Remarkable transglycosylation activity of glycosynthase mutants of endo-D, an endo-beta-N-acetylglucosaminidase from Streptococcus pneumoniae. AB - Endo-beta-N-acetylglucosaminidase from Streptococcus pneumoniae (Endo-D) is an endoglycosidase capable of hydrolyzing the Fc N-glycan of intact IgG antibodies after sequential removal of the sialic acid, galactose, and internal GlcNAc residues in the N-glycan. Endo-D also possesses transglycosylation activity with sugar oxazoline as the donor substrate, but the transglycosylation yield is low due to enzymatic hydrolysis of the donor substrate and the product. We report here our study on the hydrolytic and transglycosylation activity of recombinant Endo-D and its selected mutants. We found that Endo-D preferred core-fucosylated N-glycan for hydrolysis but favored nonfucosylated GlcNAc acceptor for transglycosylation. Several mutants showed significantly enhanced transglycosylation efficiency over the wild type enzyme. Two mutants (N322Q and N322A) were identified as typical glycosynthases that demonstrated remarkable transglycosylation activity with only marginal or no product hydrolysis activity. Kinetic studies revealed that the N322Q [corrected]and N322A glycosynthases had much higher catalytic efficiency for glycosylating the nonfucosylated GlcNAc acceptor. In comparison, the N322Q was much more efficient than N322A for transglycosylation. However, N322Q and N322A [corrected] could not take more complex N-glycan oxazoline as substrate for transglycosylation, indicating their strict substrate specificity. The usefulness of the N322Q glycosynthase was exemplified by its application for efficient glycosylation remodeling of IgG-Fc domain. PMID- 22318729 TI - STAT5 protein negatively regulates T follicular helper (Tfh) cell generation and function. AB - Recent work has identified a new subset of CD4(+) T cells named as Tfh cells that are localized in germinal centers and critical in germinal center formation. Tfh cell differentiation is regulated by IL-6 and IL-21, possibly via STAT3 factor, and B cell lymphoma 6 (Bcl6) is specifically expressed in Tfh cells and required for their lineage specification. In the current study, we characterized the role of STAT5 in Tfh cell development. We found that a constitutively active form of STAT5 effectively inhibited Tfh differentiation by suppressing the expression of Tfh-associated factors (CXC motif) receptor 5 (CXCR5), musculoaponeurotic fibrosarcoma (c-Maf), Bcl6, basic leucine zipper transcription factor ATF-like (Batf), and IL-21, and STAT5 deficiency greatly enhanced Tfh gene expression. Importantly, STAT5 regulated the expression of Tfh cell suppressor factor B lymphocyte-induced maturation protein 1 (Blimp-1); STAT5 deficiency impaired Blimp-1 expression and resulted in elevated expression of Tfh-specific genes. Similarly, inhibition of IL-2 potentiated Tfh generation, associated with dampened Blimp-1 expression; Blimp-1 overexpression inhibited Tfh gene expression in Stat5-deficient T cells, suggesting that the IL-2/STAT5 axis functions to regulate Blimp-1 expression. In vivo, deletion of STAT5 in CD4(+) T cells resulted in enhanced development of Tfh cells and germinal center B cells and led to an impairment of B cell tolerance in a well defined mouse tolerance model. Taken together, this study demonstrates that STAT5 controls Tfh differentiation. PMID- 22318730 TI - Sequence-specific recruitment of heterochromatin protein 1 via interaction with Kruppel-like factor 11, a human transcription factor involved in tumor suppression and metabolic diseases. AB - Heterochromatin protein 1 (HP1) proteins are "gatekeepers" of epigenetic gene silencing that is mediated by lysine 9 of histone H3 methylation (H3K9me). Current knowledge supports a paradigm whereby HP1 proteins achieve repression by binding to H3K9me marks and interacting to H3K9 histone methyltransferases (HMTs), such as SUV39H1, which methylate this residue on adjacent nucleosomes thereby compacting chromatin and silencing gene expression. However, the mechanism underlying the recruitment of this epigenetic regulator to target gene promoters remains poorly characterized. In the current study, we reveal for the first time a mechanism whereby HP1 is recruited to promoters by a well characterized Kruppel-like transcription factor (KLF), in a sequence-specific manner, to mediate complex biological phenomena. A PXVXL HP1-interacting domain identified at position 487-491 of KLF11 mediates the binding of HP1alpha and KLF11 in vitro and in cultured cells. KLF11 also recruits HP1alpha and its histone methyltransferase, SUV39H1, to promoters to limit KLF11-mediated gene activation. Indeed, a KLF11DeltaHP1 mutant derepresses KLF11-regulated cancer genes, by inhibiting HP1-SUV39H1 recruitment, decreasing H3K9me3, while increasing activation-associated marks. Biologically, impairment of KLF11 mediated HP1-HMT recruitment abolishes tumor suppression, providing direct evidence that HP1-HMTs act in a sequence-specific manner to achieve this function rather than its well characterized binding to methylated chromatin without intermediary. Collectively, these studies reveal a novel role for HP1 as a cofactor in tumor suppression, expand our mechanistic understanding of a KLF associated to human disease, and outline cellular and biochemical mechanisms underlying this phenomenon, increasing the specificity of targeting HP1-HMT complexes to gene promoters. PMID- 22318731 TI - Plasticity in structural and functional interactions between the phosphoprotein and nucleoprotein of measles virus. AB - The measles virus (MeV) phosphoprotein (P) tethers the polymerase to the nucleocapsid template for transcription and genome replication. Binding of P to nucleocapsid is mediated by the X domain of P (XD) and a conserved sequence (Box 2) within the C-terminal domain of the nucleoprotein (N(TAIL)). XD binding induces N(TAIL) alpha-helical folding, which in turn has been proposed to stabilize the polymerase-nucleocapsid complex, with cycles of binding and release required for transcription and genome replication. The current work directly assessed the relationships among XD-induced N(TAIL) folding, XD-N(TAIL) binding affinity, and polymerase activity. Amino acid substitutions that abolished XD induced N(TAIL) alpha-helical folding were created within Box-2 of Edmonston MeV N(TAIL). Polymerase activity in minireplicons was maintained despite a 35-fold decrease in XD-N(TAIL) binding affinity or reduction/loss of XD-induced N(TAIL) alpha-helical folding. Recombinant infectious virus was recovered for all mutants, and transcriptase elongation rates remained within a 1.7-fold range of parent virus. Box-2 mutations did however impose a significant cost to infectivity, reflected in an increase in the amount of input genome required to match the infectivity of parent virus. Diminished infectivity could not be attributed to changes in virion protein composition or production of defective interfering particles, where changes from parent virus were within a 3-fold range. The results indicated that MeV polymerase activity, but not infectivity, tolerates amino acid changes in the XD-binding region of the nucleoprotein. Selectional pressure for conservation of the Box-2 sequence may thus reflect a role in assuring the fidelity of polymerase functions or the assembly of viral particles required for optimal infectivity. PMID- 22318732 TI - MUC1-C oncoprotein induces TCF7L2 transcription factor activation and promotes cyclin D1 expression in human breast cancer cells. AB - MUC1 is a heterodimeric glycoprotein that is overexpressed in breast cancers. The present studies demonstrate that the oncogenic MUC1 C-terminal subunit (MUC1-C) associates with the TCF7L2 transcription factor. The MUC1-C cytoplasmic domain (MUC1-CD) binds directly to the TCF7L2 C-terminal region. MUC1-C blocks the interaction between TCF7L2 and the C-terminal-binding protein (CtBP), a suppressor of TCF7L2-mediated transcription. TCF7L2 and MUC1-C form a complex on the cyclin D1 gene promoter and MUC1-C promotes TCF7L2-mediated transcription by the recruitment of beta-catenin and p300. Silencing MUC1-C in human breast cancer cells down-regulated activation of the cyclin D1 promoter and decreased cyclin D1 expression. In addition, a MUC1-C inhibitor blocked the interaction with TCF7L2 and suppressed cyclin D1 levels. These findings indicate that the MUC1-C oncoprotein contributes to TCF7L2 activation and thereby promotes cyclin D1 expression in breast cancer cells. PMID- 22318733 TI - Transport of influenza virus neuraminidase (NA) to host cell surface is regulated by ARHGAP21 and Cdc42 proteins. AB - Influenza virus neuraminidase (NA) is transported to the virus assembly site at the plasma membrane and is a major viral envelope component that plays a critical role in the release of progeny virions and in determination of host range restriction. However, little is known about the host factors that are involved in regulating the intracellular and cell surface transport of NA. Here we identified the Cdc42-specific GAP, ARHGAP21 differentially expressed in host cells infected with influenza A virus using cDNA microarray analysis. Furthermore, we have investigated the involvement of Rho family GTPases in NA transport to the cell surface. We found that expression of constitutively active or inactive mutants of RhoA or Rac1 did not significantly affect the amount of NA that reached the cell surface. However, expression of constitutively active Cdc42 or depletion of ARHGAP21 promoted the transport of NA to the plasma membranes. By contrast, cells expressing shRNA targeting Cdc42 or overexpressing ARHGAP21 exhibited a significant decrease in the amount of cell surface-localized NA. Importantly, silencing Cdc42 reduced influenza A virus replication, whereas silencing ARHGAP21 increased the virus replication. Together, our results reveal that ARHGAP21- and Cdc42-based signaling regulates the NA transport and thereby impacts virus replication. PMID- 22318734 TI - Proteasomal inhibition restores biological function of mis-sense mutated dysferlin in patient-derived muscle cells. AB - Dysferlin is a transmembrane protein implicated in surface membrane repair of muscle cells. Mutations in dysferlin cause the progressive muscular dystrophies Miyoshi myopathy, limb girdle muscular dystrophy 2B, and distal anterior compartment myopathy. Dysferlinopathies are inherited in an autosomal recessive manner, and many patients with this disease harbor mis-sense mutations in at least one of their two pathogenic DYSF alleles. These patients have significantly reduced or absent dysferlin levels in skeletal muscle, suggesting that dysferlin encoded by mis-sense alleles is rapidly degraded by the cellular quality control system. We reasoned that mis-sense mutated dysferlin, if salvaged from degradation, might be biologically functional. We used a dysferlin-deficient human myoblast culture harboring the common R555W mis-sense allele and a DYSF null allele, as well as control human myoblast cultures harboring either two wild type or two null alleles. We measured dysferlin protein and mRNA levels, resealing kinetics of laser-induced plasmalemmal wounds, myotube formation, and cellular viability after treatment of the human myoblast cultures with the proteasome inhibitors lactacystin or bortezomib (Velcade). We show that endogenous R555W mis-sense mutated dysferlin is degraded by the proteasomal system. Inhibition of the proteasome by lactacystin or Velcade increases the levels of R555W mis-sense mutated dysferlin. This salvaged protein is functional as it restores plasma membrane resealing in patient-derived myoblasts and reverses their deficit in myotube formation. Bortezomib and lactacystin did not cause cellular toxicity at the regimen used. Our results raise the possibility that inhibition of the degradation pathway of mis-sense mutated dysferlin could be used as a therapeutic strategy for patients harboring certain dysferlin mis sense mutations. PMID- 22318735 TI - Mapping human protease-activated receptor 4 (PAR4) homodimer interface to transmembrane helix 4. AB - Thrombin activates platelets by binding and cleaving protease-activated receptors 1 and 4 (PAR1 and PAR4). Because of the importance of PAR4 activation on platelets in humans and mice and emerging roles for PAR4 in other tissues, experiments were done to characterize the interaction between PAR4 homodimers. Bimolecular fluorescence complementation and bioluminescence resonance energy transfer (BRET) were used to examine the PAR4 homodimer interface. In bimolecular fluorescence complementation experiments, PAR4 formed homodimers that were disrupted by unlabeled PAR4 in a concentration-dependent manner, but not by rhodopsin. In BRET experiments, the PAR4 homodimers showed a specific interaction as indicated by a hyperbolic BRET signal in response to increasing PAR4-GFP expression. PAR4 did not interact with rhodopsin in BRET assays. The threshold maximum BRET signal was disrupted in a concentration-dependent manner by unlabeled PAR4. In contrast, rhodopsin was unable to disrupt the BRET signal, indicating that the disruption of the PAR4 homodimer is not due to nonspecific interactions. A panel of rho-PAR4 chimeras and PAR4 point mutants has mapped the dimer interface to hydrophobic residues in transmembrane helix 4. Finally, mutations that disrupted dimer formation had reduced calcium mobilization in response to the PAR4 agonist peptide. These results link the loss of dimer formation to a loss of PAR4 signaling. PMID- 22318736 TI - The cellular composition of neurogenic periventricular zones in the adult zebrafish forebrain. AB - A central goal of adult neurogenesis research is to characterize the cellular constituents of a neurogenic niche and to understand how these cells regulate the production of new neurons. Because the generation of adult-born neurons may be tightly coupled to their functional requirement, the organization and output of neurogenic niches may vary across different regions of the brain or between species. We have undertaken a comparative study of six (D, Vd, Vv, Dm, Dl, Ppa) periventricular zones (PVZs) harboring proliferative cells present in the adult forebrain of the zebrafish (Danio rerio), a species known to possess widespread neurogenesis throughout life. Using electron microscopy, we have documented for the first time the detailed cytoarchitecture of these zones, and propose a model of the cellular composition of pallial and subpallial PVZs, as well as a classification scheme for identifying morphologically distinct cell types. Immunolabeling of resin-embedded tissue confirmed the phenotype of three constitutively proliferating (bromodeoxyuridine [BrdU]+) cell populations, including a radial glial-like (type IIa) cell immunopositive for both S100beta and glutamine synthetase (GS). Our data revealed rostrocaudal differences in the density of distinct proliferative populations, and cumulative labeling studies suggested that the cell cycle kinetics of these populations are not uniform between PVZs. Although the peak numbers of differentiated neurons were generated after ~2 weeks among most PVZs, niche-specific decline in the number of newborn neurons in some regions occurred after 4 weeks. Our data suggest that the cytoarchitecture of neurogenic niches and the tempo of neuronal production are regionally distinct in the adult zebrafish forebrain. PMID- 22318737 TI - What's the "go to" anticoagulant for stroke prevention in atrial fibrillation? PMID- 22318738 TI - A method for screening for the risk of chronic effects of surface water pollution. AB - The article describes a method for screening for the risk of chronic surface water pollution which was developed at the T. G. Masaryk Water Research Institute. The approach, which is based on exotoxicological analyses, can be classed as a rapid method of assessment. The degree of risk of chronic effects surface water pollution is determined from an evaluation of two major parameters toxicity and genotoxicity. As the method utilizes relative simple procedures for sample collection, pretreatment of the sample, chemical analyses, bioassays and results assessment, this approach is suitable for widespread practical use. Extensive utilization of this approach for assessing river basins in the Czech Republic has proved its suitability for a more sophisticated detection of the biological impact of surface water pollution. This is documented in the article where the method is used in a study of the Bilina River, and in the overview of the results of the risk assessment of chronic effects of surface water pollution in selected sections of three international river basins in the Czech Republic. PMID- 22318739 TI - Modelling geosmin concentrations in three sources of raw water in Quebec, Canada. AB - The presence of off-flavour compounds such as geosmin, often found in raw water, significantly reduces the organoleptic quality of distributed water and diverts the consumer from its use. To adapt water treatment processes to eliminate these compounds, it is necessary to be able to identify them quickly. Routine analysis could be considered a solution, but it is expensive and delays associated with obtaining the results of analysis are often important, thereby constituting a serious disadvantage. The development of decision-making tools such as predictive models seems to be an economic and feasible solution to counterbalance the limitations of analytical methods. Among these tools, multi-linear regression and principal component regression are easy to implement. However, due to certain disadvantages inherent in these methods (multicollinearity or non-linearity of the processes), the use of emergent models involving artificial neurons networks such as multi-layer perceptron could prove to be an interesting alternative. In a previous paper (Parinet et al., Water Res 44: 5847-5856, 2010), the possible parameters that affect the variability of taste and odour compounds were investigated using principal component analysis. In the present study, we expand the research by comparing the performance of three tools using different modelling scenarios (multi-linear regression, principal component regression and multi-layer perceptron) to model geosmin in drinking water sources using 38 microbiological and physicochemical parameters. Three very different sources of water, in terms of quality, were selected for the study. These sources supply drinking water to the Quebec City area (Canada) and its vicinity, and were monitored three times per month over a 1-year period. Seven different modelling methods were tested for predicting geosmin in these sources. The comparison of the seven different models showed that simple models based on multi-linear regression provide sufficient predictive capacity with performance levels comparable to those obtained with artificial neural networks. The multi-linear regression model (R(2) = 0.657, <0.001) used only four variables (phaeophytin, sum of green algae, chlorophyll-a and potential Redox) in comparison with ten variables (potassium, heterotrophic bacteria, organic nitrogen, total nitrogen, phaeophytin, total organic carbon, sum of green algae, potential Redox, UV absorbance at 254 nm and atypical bacteria) for the best model obtained with artificial neural networks (R(2) = 0.843). PMID- 22318740 TI - Evaluating the metallic pollution of riverine water and sediments: a case study of Aras River. AB - Metallic pollution caused by elements Zn, Cu, Fe, Pb, Ni, Cd, and Hg in water and sediments of Aras River within a specific area in Ardabil province of Iran is considered. Water and sediment samples were collected seasonally and once respectively from the five selected stations. Regarding WHO published permissible values, only Ni concentration in spring and summer water samples has exceeded the acceptable limit up to four times greater than the limit. The concentration of metals Ni, Pb, and Fe in river water shows a direct relationship with river water discharge and the amount of precipitation. Enhanced soil erosion, bed load dissolution, and runoffs may play a key role in remarkable augmentation of metallic ions concentration. Furthermore, excessive use of pesticides which contain a variety of metallic ions (mainly Cu) in spring and summer may also result in an increase in the metals' concentration. The potential risk of Ni exposure to the water environment of the study area is assigned to juice, dairy products, edible oil, and sugar cane factories as well as soybean crop lands which are located within the sub-basin of Aras River in the study area. Regarding the sediment samples, the bioavailable metal concentrations indicate an ascending order from the first station towards the last one. In comparison with earth crust, sedimental and igneous rocks the reported metallic concentration values, except for Cd, lie within the low-risk status. Regarding Cd, the reported values in some stations (S2, S4, and S5) are up to ten times greater than that of shale which may be considered as a remarkable risk potential. The industrial and municipal wastewater generated by Parsabad moqan industrial complex and residential areas, in addition to the discharges of animal husbandry centers, may be addressed as the key factors in the sharp increase of metallic pollution potential in stations 4 and 5. PMID- 22318741 TI - Heavy metal concentration in sediment, benthic, benthopelagic, and pelagic fish species from Musa Estuary (Persian Gulf). AB - The concentration of Cd, Co, Cu, Ni, and Pb was measured in sediment and three fish species collected from Musa Estuary, Persian Gulf. The concentration order of heavy metals in sediment were Ni > Co > Cu > Pb > Cd >. Concentrations of the heavy metals in the fish were apparently different among the three species. The concentrations of Cd and Ni in fish were Johnius belangerii > Euryglossa orientalis > Liza abu, while the Co and Cu levels were L. abu > E. orientalis > J. belangerii and E. orientalis > L. abu > J. belangerii, respectively. Result of regression analysis showed that there were no significant relationships between metal concentration in fish tissues and sediment, except for Ni concentration in the J. belangerii liver. The concentrations of studied metals in fish muscle were below the permissible limits proposed by FAO, WHO, and EC. PMID- 22318742 TI - Comparing effects of lacidipine, ramipril, and valsartan against experimentally induced myocardial infarcted rats. AB - In this study, the effects of lacidipine (LAC), ramipril (RAM), and valsartan (VAL) on biochemical and histopathologic changes in heart tissue were studied in rats with isoproterenol-induced (ISO-induced) myocardial infarction (MI). LAC, RAM, and VAL had been administered via oral gavage at 3, 3, and 30 mg/kg doses, respectively, once per day during a 30-day time period. On days 29 and 30, the drug treatment group and the control group (with the exception of the intact control group, in which no medications were given, and ISO was not administered) were administered 180 mg/kg ISO subcutaneously over an interval of 24 h. After this period, the hearts of the rats were removed and processed for biochemical and histopathologic studies. The antioxidant parameters superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were estimated. A diagnosis of MI was confirmed with antioxidant parameters and histopathologic findings. In MI control groups, histopathologic indicators were found to be statistically higher than those in drug groups; an increase in histopathologic indicators of MI correlates with significant decreases in SOD and CAT levels, and an increase in MDA level. Histopathologic grades of MI indicators were significantly higher in MI group that did not receive any cardioprotective medications in comparison with MI groups that received LAC, RAM, and VAL. Each of the three medications favorably modulated most of the biochemical and histopathologic parameters observed. No significant difference existed with regard to any of the estimated parameters in the rat groups that received medications without MI induction. In conclusion, results indicate that LAC, RAM, and VAL significantly reduced myocardial injury and emphasize the cardioprotective nature of these agents. PMID- 22318743 TI - Reduced bone mineral density in patients with haemophilia A and B in Northern Greece. AB - Haemophilia A and B has been associated with increased prevalence of low bone mass (67-86%). The aim of this study was to estimate the prevalence of bone disease in haemophiliacs and its association with potential risk factors. Adult patients with haemophilia A and B followed-up in the Haemophilia Centre of Northern Greece were included. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA) in lumbar spine (LS), femoral neck (FN), total hip (TH) and great trochanter (GT). One-hundred four male patients (aged 45.8 +/- 15.1 years) and 50 controls (aged 44.9 +/- 12.8 years) were screened. Low BMD was diagnosed in 28 patients (26.9%) and 10 controls (20%) (p=0.0001). Patients had lower BMD in TH (p=0.007), FN (p=0.029) and GT (p=0.008) than controls, without differences in LS. BMD was positively associated with the severity of haemophilia, history of herpes virus C or human immunodeficiency virus and level of physical activity, and negatively with the level of arthropathy. In multiple regression analysis, only the level of physical activity and 25-hydroxyvitamin D [25(OH)D] significantly predicted BMD. Half of the patients had vitamin D deficiency. In conclusion, our study showed increased prevalence of low BMD in haemophiliacs. The levels of physical activity and 25(OH)D independently predicted low BMD. PMID- 22318744 TI - Counting the cost of cancer surgery for advanced and metastatic disease. PMID- 22318745 TI - Volatile compounds and antioxidative activity of Porophyllum tagetoides extracts. AB - Porophyllum tagetoides is an annual warm-weather herb that has an intense typical smell. Its leaves are commonly used in soup preparation and traditional medicine for treatment of inflammatory diseases. Its volatile compounds and antioxidant properties were evaluated in crude, aqueous and ethanol leaf extract and an oil emulsion using different antioxidant assays in vitro, such as: DPPH radical scavenging activity, redox potential, polyphenol content, reducing power and optical density. A high antioxidative activity was found when comparing leaves with stems. The crude extract from leaves showed a very high reducing power (2.88 +/- 0.20 O.D.) and DPPH radical-scavenging activity (54.63 +/- 4.80%), in concordance with a major concentration of vitamin C (23.97 +/- 0.36 mg/100 g). Instead, the highest polyphenol content (264.54 +/- 2.17 mg GAE/g of sample) and redox potential (561.23 +/- 0.15 mV) were found by the ethanol and aqueous extract, respectively. Aldehydes and terpenes such as nonanal, decanal, trans pineno, beta-myrcene and D-limonene were the major volatiles found. This study suggests that Porophyllum tagetoides extracts could be used as antioxidants. PMID- 22318746 TI - Fifteen years of GH replacement increases bone mineral density in hypopituitary patients with adult-onset GH deficiency. AB - OBJECTIVE: Few studies have determined the effects of more than 5-10 years of GH replacement in adults on bone mineral content (BMC) and bone mineral density (BMD). DESIGN/PATIENTS: In this prospective, single-centre, open-label study, the effects of 15 years of GH replacement on BMC and BMD, measured using dual-energy X-ray absorptiometry, were determined in 126 hypopituitary adults (72 men) with adult-onset GH deficiency (GHD). Mean age was 49.4 (range 22-74) years at the initiation of the study. RESULTS: The mean initial GH dose of 0.63 (s.e.m. 0.03) mg/day was gradually lowered to 0.41 (0.01) mg/day after 15 years. The mean serum IGF1 SDS increased from -1.69 (0.11) at baseline to 0.63 (0.16) at the study end (P<0.001 vs baseline). The 15 years of GH replacement induced a sustained increase in total body BMC (+5%, P<0.001) and BMD (+2%, P<0.001). Lumbar (L2-L4) spine BMC increased by 9% (P<0.001) and BMD by 5% (P<0.001). In femur neck, a peak increase in BMC and BMD of 7 and 3%, respectively, was observed after 7 years (both P<0.001). After 15 years, femur neck BMC was 5% above the baseline value (P<0.01), whereas femur neck BMD had returned to the baseline level. In most variables, men had a more marked response to GH replacement than women. CONCLUSIONS: Fifteen-year GH replacement in GHD adults induced a sustained increase in total body and lumbar (L2-L4) spine BMC and BMD. In femur neck, BMC and BMD peaked at 7 years and then decreased towards baseline values. PMID- 22318747 TI - Functional and total IGFBP3 for the assessment of disorders of the GH/IGF1 axis in children with chronic kidney disease, GH deficiency, or short stature after SGA status at birth. AB - OBJECTIVE: IGFBP3 immunoreactivity may appear elevated in patients with chronic kidney disease (CKD), in part due to accumulation of low molecular fragments. The importance of these IGFBP3 variants for binding and inactivation of IGF1 and their relevance for the impaired growth of uremic children are unclear. Nevertheless, IGFBP3, measured as total (t-)IGFBP3, is frequently used as a diagnostic parameter in pediatric CKD patients. A new assay for functional (f )IGFBP3 exclusively detects IGFBP3 capable of IGF binding. The aim of the study was to evaluate the significance of f-IGFBP3 measurements for the assessment of uremic abnormalities of the GH/IGF1 axis. DESIGN: Prospective cross-sectional study. METHODS: t-IGFBP3, f-IGFBP3, and IGF1 were measured in pediatric CKD patients, including patients with CKD stage 3-4 not on dialysis (CKD, n=33), on dialysis treatment (DT, n=26), patients after renal transplantation (RTx, n=89), healthy children (n=29), children with GH deficiency (GHD, n=42), and small for gestational age (SGA) children (SGA, n=34). RESULTS: Mean t-IGFBP3 SDS was elevated in CKD, DT, and RTx children compared with controls and GHD patients (P<=0.0004). Highest values were reached in DT (P<0.0001 vs all groups). In contrast, mean f-IGFBP3 was similar in all groups (P=0.30). CONCLUSIONS: Pediatric CKD patients displayed elevated serum concentrations of t-IGFBP3 but not f-IGFBP3, supporting the hypothesis that IGFBP3 fragments not binding IGF1 accumulate during uremia. f-IGFBP3 is an indicator of IGFBP3 fragmentation and seems to reflect IGF1 binding in CKD better than t-IGFBP3. However, the role of f IGFBP3 for the diagnosis of disturbances of the GH/IGF hormonal axis appears to be limited. PMID- 22318748 TI - Effects of growth environments and two environmental endocrine disruptors on children with idiopathic precocious puberty. AB - OBJECTIVE: The incidence of idiopathic precocious puberty (IPP) might have an increasing trend. But the causes and risk factors of IPP are unknown. The objective of our study is to evaluate the effects of growth environments and two environmental endocrine disruptors (EDCs), zearalenone (ZEA), and 1,1-dichloro 2,2,bisethylene (p,p'-DDE), on patients with IPP. DESIGN: Case-control study. METHODS: The study consisted of 78 IPP patients at diagnosis and 100 control children matched for age and sex. A questionnaire was designed to collect data on growth environments, and serum ZEA and p,p'-DDE were tested in all subjects. We analyzed data on growth environments, two EDCs, and biological interaction between growth environments and EDCs. RESULTS: In growth environments, small for gestational age, maternal physical disease during pregnancy, early maternal menarche, early puberty of same-degree relatives, and father's absence in 4- to 6 year olds were risk factors for children with IPP (P<0.05). Serum ZEA concentration, ZEA, and p,p'-DDE-positive rates in the IPP group were significantly higher than those in the control group (P<0.05). There was a biological interaction between growth environments and ZEA (relative excess risk due to interaction =34.562, attributable proportion due to interaction =0.745, synergy index =4.193). CONCLUSIONS: Results suggest possible effects of growth environments and two EDCs on the development of IPP. In addition, growth environments and ZEA have biological interaction that might increase the risk of developing IPP. PMID- 22318751 TI - Body mass index and the risk for developing invasive breast cancer among high risk women in NSABP P-1 and STAR breast cancer prevention trials. AB - High body mass index (BMI) has been associated with an increased risk for breast cancer among postmenopausal women. However, the relationship between BMI and breast cancer risk in premenopausal women has remained unclear. Data from two large prevention trials conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) were used to explore the relationship between baseline BMI and breast cancer risk. The analyses included 12,243 participants with 253 invasive breast cancer events from the Breast Cancer Prevention Trial (P-1) and 19,488 participants with 557 events from the Study of Tamoxifen and Raloxifene (STAR). Both studies enrolled high-risk women (Gail score >= 1.66) with no breast cancer history. Women in P-1 were pre- and postmenopausal, whereas women in STAR (P-2) were all postmenopausal at entry. Using Cox proportional hazards regression, we found slight but nonsignificant increased risks of invasive breast cancer among overweight and obese postmenopausal participants in STAR and P-1. Among premenopausal participants, an increased risk of invasive breast cancer was significantly associated with higher BMI (P = 0.01). Compared with BMI less than 25, adjusted HRs for premenopausal women were 1.59 for BMI 25 to 29.9 and 1.70 for BMI 30 or more. Our investigation among annually screened, high-risk participants in randomized, breast cancer chemoprevention trials showed that higher levels of BMI were significantly associated with increased breast cancer risk in premenopausal women older than 35 years, but not postmenopausal women. PMID- 22318752 TI - Oncogenic function and early detection potential of miRNA-10b in oral cancer as identified by microRNA profiling. AB - The miRNA participates in a variety of biologic processes, and dysregulation of miRNA is associated with malignant transformation. In this study, we determined specific profile of miRNA associated with oral cancer by using miRNA array screening method. There were 23 miRNAs found with considerably differential expressions between six oral cancer cell lines and five lines of normal oral keratinocytes, in which, 10 miRNAs showed the highest significant difference after independent examination by reverse transcription quantitative PCR. Eight molecules were upregulated, miR-10b, miR-196a, miR-196b, miR-582-5p, miR-15b, miR 301, miR-148b, and miR-128a, and two molecules, miR-503 and miR-31, were downregulated. The most upregulated miR-10b was further examined, and its functions were characterized in two oral cancer cell lines. The miR-10b actively promotes cell migration (2.6- to 3.6-fold) and invasion (1.7- to 1.9-fold) but has minimal effect on cell growth or chemo-/radiosensitivity. Furthermore, miR 10b was considerably elevated in the plasma of xenografted tumor mice (20-fold). This upregulation of miR-10b in plasma was further shown in the patients with oral cancer [P < 0.0001, area under curve (AUC) = 0.932] and precancer lesions (P < 0.0001, AUC = 0.967), suggesting that miR-10b possesses a high potential to discriminate the normal subjects. In conclusion, we have identified at least 10 miRNAs significantly associated with oral cancer, including the most elevated miR 10b. The miR-10b actively participates in cancer formation by promoting cell migration and invasion. Our study using clinical samples suggests that plasma miR 10b has high potential as an early detection marker for oral cancer. PMID- 22318753 TI - Protection of humans by plant glucosinolates: efficiency of conversion of glucosinolates to isothiocyanates by the gastrointestinal microflora. AB - Plant-based diets rich in crucifers are effective in preventing cancer and other chronic diseases. Crucifers contain very high concentrations of glucosinolates (GS; beta-thioglucoside-N-hydroxysulfates). Although not themselves protective, GS are converted by coexisting myrosinases to bitter isothiocyanates (ITC) which defend plants against predators. Coincidentally, ITC also induce mammalian genes that regulate defenses against oxidative stress, inflammation, and DNA-damaging electrophiles. Consequently, the efficiency of conversion of GS to ITC may be critical in controlling the health-promoting benefits of crucifers. If myrosinase is heat-inactivated by cooking, the gastrointestinal microflora converts GS to ITC, a process abolished by enteric antibiotics and bowel cleansing. When single oral doses of GS were administered as broccoli sprout extracts (BSE) to two dissimilar populations (rural Han Chinese and racially mixed Baltimoreans) patterns of excretions of urinary dithiocarbamates (DTC) were very similar. Individual conversions in both populations varied enormously, from about 1% to more than 40% of dose. In contrast, administration of ITC (largely sulforaphane) containing BSE resulted in uniformly high (70%-90%) conversions to urinary DTC. Despite the remarkably large range of conversion efficiencies between individuals, repeated determinations within individuals were much more consistent. The rates of urinary excretion (slow or fast) were unrelated to the ultimate magnitudes (low or high) of these conversions. Although no demographic factors affecting conversion efficiency have been identified, there are clearly diurnal variations: conversion of GS to DTC was greater during the day, but conversion of ITC to DTC was more efficient at night. PMID- 22318754 TI - Effects of menthol on the pharmacokinetics of bupropion among Black smokers. AB - INTRODUCTION: Despite the widespread use of mentholated cigarettes, lower cessation rates, and disproportionately high smoking-related morbidity among Blacks, the possible role of menthol in smokers' response to pharmacotherapy has not been well-studied. This study examined the effects of menthol on the pharmacokinetic (PK) profiles of bupropion and its principal metabolites, hydroxybupropion, threohydrobupropion, and erythrohydrobupropion among Black smokers. METHODS: After a 7-day placebo run-in period, participants received 150 mg bid sustained-release bupropion for 20-25 days. Blood samples were drawn for PK analysis on 2 occasions, 10-15 days after the commencement of bupropion while participants were still smoking (smoking phase) and at days 20-25 when they were asked not to smoke (nonsmoking phase). RESULTS: 18 smokers of nonmenthol cigarettes and 23 smokers of menthol cigarettes were enrolled in this study. No differences were found by menthol smoking status in the Cmax and area under the plasma concentration versus time curve (AUC) of bupropion and its metabolites in the smoking or nonsmoking phases. However, among menthol smokers, the AUC ratios of metabolite/bupropion were lower in the nonsmoking phase compared with the smoking phase (hydro/bup = 31.49 +/- 18.84 vs. 22.95 +/- 13.27, p = .04; erythro/bup = 1.99 +/- 1.02 vs. 1.76 +/- 0.75, p = .016; threo/bup = 11.77 +/- 8.90 vs. 10.44 +/- 5.63, p = .034). No significant differences were found in the metabolite/bup ratios between smoking and nonsmoking conditions among nonmenthol smokers. CONCLUSIONS: We did not find a significant effect of menthol compared with nonmenthol cigarette smoking on the PKs of bupropion and metabolites at steady state. More research is needed to advance the understanding of mechanisms underlying disparities in smoking cessation outcomes related to smoking of menthol cigarettes. PMID- 22318755 TI - Evidence-based practice: a critical appraisal. PMID- 22318757 TI - Atrial fibrillation and acid reflux disease. AB - To date, the precise mechanism of atrial fibrillation (AF) as a possible cause of reflux disease remains uncertain, although some possibilities can be postulated. Inflammation and vagal stimulation may have a key role linking these 2 common diseases. There is some evidence in the form of case reports and limited observational studies reporting that reflux disease, and more specifically esophagitis, can cause paroxysmal AF, and various mechanisms have been proposed. Some studies have demonstrated that acid suppressive therapy by proton pump inhibitors (PPIs) may help ameliorate symptoms associated with AF and also facilitate conversion to normal sinus rhythm in a subset of patients. Further prospective studies are needed to determine if a true causal mechanism exists between the two and assess whether the mechanism is dependent on a specific subtype of AF. In addition, the response of AF-related symptoms to PPI therapy and the potential for PPI therapy to reduce the development of AF merits further investigation. PMID- 22318756 TI - Bisphosphonates: effects on osteoblast. AB - PURPOSE: Bisphosphonates are synthetic analogues of pyrophosphate usually used in treating bone disorders such as osteoporosis, Paget's disease, fibrous dysplasia, hypercalcemia of malignancy, and inflammation-related bone loss. Though therapeutic effects of bisphosphonates depend primarily on their inhibitory effect on osteoclasts, increasing attention is being given to other effector cells, such as osteoblasts. This review focuses on the presumed effect of bisphosphonates on osteoblasts. METHODS: A review of the literature was conducted to evaluate the pharmacodynamic effects of bisphosphonates including inhibition of osteoclasts and apoptosis of osteocytes and osteoblasts as well as their potential stimulatory effects on the proliferation of osteoblasts. RESULTS: Studies have demonstrated that bisphosphonates may stimulate proliferation of osteoblasts and inhibit apoptosis of osteocytes and osteoblasts. CONCLUSION: Considering that osteoblasts may be involved in bone disorders, such as osteoporosis, osteopetrosis, osteogenesis imperfecta, and Paget's disease, and that bisphosphonates may stimulate proliferation of osteoblasts and inhibit apoptosis of osteocytes and osteoblasts, it is conceivable that a role for bisphosphonates exists in these diseases beyond merely the osteoclast influence. PMID- 22318758 TI - Very-low-calorie diet: a quick therapeutic tool to improve beta cell function in morbidly obese patients with type 2 diabetes. AB - BACKGROUND: Caloric restriction in obese diabetic patients quickly improves glucose control, independently from weight loss. However, the early effects of a very-low-calorie diet (VLCD) on insulin sensitivity and insulin secretion in morbidly obese patients with type 2 diabetes are still unclear. OBJECTIVE: The objective was to study the relative contributions of insulin sensitivity, insulin secretion, or both to improvement in glucose metabolism, after 1 wk of caloric restriction, in severely obese diabetic patients. DESIGN: Hyperglycemic clamps were performed in 14 severely obese (BMI, in kg/m(2): >40) patients with type 2 diabetes in good glucose control (glycated hemoglobin < 7.5%) before and after 7 d of a VLCD (400 kcal/d). RESULTS: The VLCD caused a 3.22 +/- 0.56% weight loss (P < 0.001), 42.0% of which was fat loss, accompanied by decreases in fasting plasma glucose (P < 0.05) and triglycerides (P < 0.01). In parallel, the Disposition Index, which measures the body's capability to dispose of a glucose load, increased from 59.0 +/- 6.3 to 75.5 +/- 6.3 mL. min(-1) . m(-2) body surface area (P < 0.01), because of improvements in indexes of both first- and second-phase insulin secretion (P < 0.02), but with no changes in insulin sensitivity (P = 0.33). CONCLUSION: The marked improvement in metabolic profile, observed in severely obese patients with type 2 diabetes after a 7-d VLCD, was primarily due to the amelioration of beta cell function, whereas no contribution of insulin sensitivity was shown. This trial was registered at www.clinicaltrials.gov as NCT01447524. PMID- 22318759 TI - Effect of hereditary haemochromatosis genotypes and iron overload on other trace elements. AB - PURPOSE: Hereditary haemochromatosis is a common genetic disorder involving dysregulation of iron absorption. There is some evidence to suggest that abnormal iron absorption and metabolism may influence the status of other important trace elements. In this study, the effect of abnormal HFE genotypes and associated iron overload on the status of other trace elements was examined. METHODS: Dietary data and blood samples were collected from 199 subjects (mean age = 55.4 years; range = 21-81 years). Dietary intakes, serum selenium, copper and zinc concentrations and related antioxidant enzymes (glutathione peroxidase and superoxide dismutase) in subjects with normal HFE genotype (n = 118) were compared to those with abnormal HFE genotype, with both normal iron status (n = 42) and iron overload (n = 39). RESULTS: For most dietary and biochemical variables measured, there were no significant differences between study groups. Red cell GPx was significantly higher in male subjects with normal genotypes and normal iron status compared to those with abnormal genotypes and normal iron status (P = 0.03) or iron overload (P = 0.001). Red cell GPx was also highest in normal women and significantly lower in the abnormal genotype and normal iron group (P = 0.016), but not in the iron overload group (P = 0.078). CONCLUSION: Although it may not be possible to exclude a small effect between the genotype groups on RBC GPx, overall, haemochromatosis genotypes or iron overload did not appear to have a significant effect on selenium, copper or zinc status. PMID- 22318760 TI - Motor and tactile-perceptual skill differences between individuals with high functioning autism and typically developing individuals ages 5-21. AB - We examined motor and tactile-perceptual skills in individuals with high functioning autism (IHFA) and matched typically developing individuals (TDI) ages 5-21 years. Grip strength, motor speed and coordination were impaired in IHFA compared to matched TDI, and the differences between groups varied with age. Although tactile-perceptual skills of IHFA were impaired compared to TDI on several measures, impairments were significant only for stereognosis. Motor and tactile-perceptual skills should be assessed in children with IHFA and intervention should begin early because these skills are essential to school performance. Impairments in coordination and stereognosis suggest a broad though selective under-development of the circuitry for higher order abilities regardless of domain that is important in the search for the underlying disturbances in neurological development. PMID- 22318761 TI - Measurement of epithelial thickness within the oral cavity using optical coherence tomography. AB - BACKGROUND: The purpose of the present study was to determine normal values of epithelial thickness within the oral cavity by using optical coherence tomography (OCT). METHODS: In a total of 143 healthy test persons, epithelial thickness of the oral mucosa was determined with the help of OCT separately for each side at 7 different locations. Special attention was directed to those sites having the highest incidence for the development of dysplasias and carcinomas. RESULTS: The epithelium demonstrated a varying thickness depending on its location within the oral cavity. The highest values were found in the region of the buccal mucosa (294 MUm) and the hard palate (239 MUm), whereas the thinnest epithelium was measured at the floor of the mouth (99 MUm). CONCLUSION: Our data serve as reference values for detecting oral malignancy and determining the approximate grade of dysplasia. In this circumstance, a differentiated view of the different regions is important due to a variation in thickness of the epithelium within the oral cavity. PMID- 22318762 TI - Resting amygdala and medial prefrontal metabolism predicts functional activation of the fear extinction circuit. AB - OBJECTIVE: Individual differences in a person's ability to control fear have been linked to activation in the dorsal anterior cingulate cortex, the ventromedial prefrontal cortex, and the amygdala. This study investigated whether functional variance in this network can be predicted by resting metabolism in these same regions. METHOD: The authors measured resting brain metabolism in healthy volunteers with positron emission tomography using [18F]fluorodeoxyglucose. This was followed by a 2-day fear conditioning and extinction training paradigm using functional MRI to measure brain activation during fear extinction and recall. The authors used skin conductance response to index conditioned responding, and they used resting metabolism in the amygdala, the dorsal anterior cingulate cortex, and the ventromedial prefrontal cortex to predict responses during fear extinction and extinction recall. RESULTS: During extinction training, resting amygdala metabolism positively predicted activation in the ventromedial prefrontal cortex and negatively predicted activation in the dorsal anterior cingulate cortex. In contrast, during extinction recall, resting amygdala metabolism negatively predicted activation in the ventromedial prefrontal cortex and positively predicted activation in the dorsal anterior cingulate cortex. In addition, resting metabolism in the dorsal anterior cingulate cortex predicted fear expression (as measured by skin conductance response) during extinction recall. CONCLUSIONS: Resting brain metabolism predicted neuronal reactivity and skin conductance changes associated with the recall of the fear extinction memory. PMID- 22318763 TI - The interaction of parental history of suicidal behavior and exposure to adoptive parents' psychiatric disorders on adoptee suicide attempt hospitalizations. AB - OBJECTIVE: The authors examined the risk of suicide attempt or other psychiatric hospitalization among adoptees whose biological parents died from or were hospitalized for suicidal behavior (BPSB) relative to adoptees whose biological parents had a psychiatric hospitalization but never for suicide attempt (BPPH). The authors examined whether risk was moderated by having an adoptive parent who had a psychiatric hospitalization during the adoptee's childhood or adolescence. METHOD: This retrospective cohort study used national longitudinal population based Swedish registry data from 1973 to 2003 to identify 2,516 adoptees with BPSB and 5,875 adoptees with BPPH. Cox regression models compared the risk for suicide attempt and other psychiatric hospitalization in the two groups. RESULTS: The interaction of BPSB with adoptive mothers' psychiatric hospitalization while the adoptee was younger than 18 years old increased the risk for an adoptee's suicide attempt. Neither BPSB nor psychiatric hospitalization among adoptive mothers alone placed adoptees at greater risk for suicide attempt hospitalizations. The interaction results were specific to adoptee suicide attempt. CONCLUSIONS: Exposure to the hospitalization of an adoptive mother because of a psychiatric disorder amplified an adoptee's risk for suicide attempt hospitalization among those adoptees at high genetic risk of suicide or suicide attempt. These results imply that suicide attempts among those at biological risk might be prevented with the early recognition and care of parental psychiatric illness. PMID- 22318764 TI - Peroxisome proliferator-activated receptor alpha induction of uncoupling protein 2 protects against acetaminophen-induced liver toxicity. AB - Acetaminophen (APAP) overdose causes acute liver failure in humans and rodents due in part to the destruction of mitochondria as a result of increased oxidative stress followed by hepatocellular necrosis. Activation of the peroxisome proliferator-activated receptor alpha (PPARalpha), a member of the nuclear receptor superfamily that controls the expression of genes encoding peroxisomal and mitochondrial fatty acid beta-oxidation enzymes, with the experimental ligand Wy-14,643 or the clinically used fibrate drug fenofibrate, fully protects mice from APAP-induced hepatotoxicity. PPARalpha-humanized mice were also protected, whereas Ppara-null mice were not, thus indicating that the protection extends to human PPARalpha and is PPARalpha-dependent. This protection is due in part to induction of the PPARalpha target gene encoding mitochondrial uncoupling protein 2 (UCP2). Forced overexpression of UCP2 protected wildtype mice against APAP induced hepatotoxicity in the absence of PPARalpha activation. Ucp2-null mice, however, were sensitive to APAP-induced hepatotoxicity despite activation of PPARalpha with Wy-14,643. Protection against hepatotoxicity by UCP2-induction through activation of PPARalpha is associated with decreased APAP-induced c-jun and c-fos expression, decreased phosphorylation of JNK and c-jun, lower mitochondrial H(2)O(2) levels, increased mitochondrial glutathione in liver, and decreased levels of circulating fatty acyl-carnitines. These studies indicate that the PPARalpha target gene UCP2 protects against elevated reactive oxygen species generated during drug-induced hepatotoxicity and suggest that induction of UCP2 may also be a general mechanism for protection of mitochondria during fatty acid beta-oxidation. PMID- 22318765 TI - Presacral Extramedullary Hematopoiesis in a Patient with Rectal Adenocarcinoma: Report of a Case and Literature Review. PMID- 22318766 TI - Cosolvent effects on the drug release and depot swelling in injectable in situ depot-forming systems. AB - Although injectable depot-forming solutions have been commercialized, the factors that influence the overall release kinetics from such systems are still not fully understood. In this work, we address the effect of cosolvent on the issue of excessive burst release of potent bioactives from injectable depot-forming solutions. Specifically, we have evaluated the influence of addition of a relatively hydrophobic cosolvent (triacetin) to more hydrophilic biocompatible solvents such as dimethyl sulfoxide (DMSO) and N-methyl-2-pyrrolidone (NMP) on the burst release. Drug release and solvent release results demonstrate that high burst release that occurred when only hydrophilic solvent was used as solvent was significantly reduced by adding triacetin as a cosolvent. The profiles of drug release were in good agreement with the profiles of the hydrophilic solvent DMSO or NMP release, and the suppression of the burst by triacetin addition is due to the suppression of the solvent release. Surprisingly, the swelling of the depot increased with triacetin amount and the depot morphology became more porous compared with the absence of triacetin. Usage of hydrophobic solvent as a cosolvent to reduce the burst release was shown to be more effective on the hydrophobic PdlLA depot and less effective on the relatively hydrophilic RG502 depot. PMID- 22318767 TI - Construction and expression of anti-Tn-antigen-specific single-chain antibody genes from hybridoma producing MLS128 monoclonal antibody. AB - Anti-Tn-antigen monoclonal antibody MLS128 has affinity for three consecutive Tn antigens (Tn3) more than Tn2. The major aim of this study was to isolate genes encoding MLS128 variable domains to produce a large quantity of recombinant MLS128 antibodies, in turn, allowing the conduct of studies on precise interactions between Tn3- or Tn2-epitopes and MLS128. This study describes cloning of the variable region genes of MLS128, construction of the variable region genes in single-chain variable fragments (scFv) and two scFvs conjugated with human IgG(1) hinge and Fc regions (scFv-Fc) types, and their respective expression in bacterial and mammalian cell. MLS128 scFv protein with the expected specificity and affinity was successfully prepared from inclusion bodies accumulating in Escherichia coli. Construction, expression and purification of two types of MLS128-scFv-Fc proteins with differing linker lengths in Chinese hamster ovary cells demonstrated that the purified scFv-Fc proteins had binding activity specific to the glycoprotein-expressing Tn-antigen clusters. These results revealed that VL and VH genes cloned from the hybridoma represent those of MLS128 and that recombinant antibodies produced from these genes should provide sufficient amounts of binding domains for use in 3D structural studies such as NMR and X-ray analysis. PMID- 22318768 TI - The prevalence of bovine venereal campylobacteriosis in cattle herds in the Lake Chad basin of Nigeria. AB - The prevalence of bovine venereal campylobacteriosis (BVC) was investigated in the Lake Chad basin of Nigeria. Preputial washings and cervico-vaginal mucus samples were obtained from 270 cattle presenting a history of abortion and lowered fertility, kept in traditional and institutional farms. All the samples investigated were cultured using standard bacteriological technique. Campylobacter fetus was isolated from six bulls and four cows. In all cattle sampled, the isolation rates were 2.2% for C. fetus subsp. venerealis and 1.5% for C. fetus subsp. fetus; the herd and within-herd prevalence rates for C. fetus were 22.2% and 3.4%, respectively, while the overall active infectivity rate was 3.7%. BVC probably contributes to lowered fertility and abortions found in cattle in the Lake Chad basin of Nigeria, associated more with C. fetus subsp. venerealis than C. fetus subsp. fetus. PMID- 22318769 TI - Detection of Pasteurella multocida isolates from local pigs of India by polymerase chain reaction and their antibiogram. AB - Pasteurella multocida has been recognized as an important veterinary pathogen for over a century. Conventional methods for diagnosis of pasteurellosis rely on the detection of the organism by microscopy and its isolation and identification. However, as far as pasteurellosis is concerned, it is not just sufficient to know the identity of the organism. To constitute effective control measures, it is important to know the serotype of the organism. A study was undertaken to characterize the Pasteurella isolates from local pigs in India with clinical respiratory disease by determination of their capsule types and presence or absence of toxin gene. Pasteurella could be isolated from 66.70% of pigs with clinical respiratory disease. All the isolates were confirmed through biochemical characterization and P. multocida-specific polymerase chain reaction. It has also been observed that all the isolates belonged to capsular type D. All the isolates were sensitive to chloramphenicol, chlortetracycline, doxycycline, and enrofloxacin, while the rest of the antibiotics were less effective. It has also been observed that all isolates were resistant to cephalexin, penicillin G, and sulphadiazine. The study revealed the detection of P. multocida serotype D from clinical respiratory diseases of local pigs of India, which could be one of the important respiratory tract pathogens responsible for mortality of local pigs in India. PMID- 22318771 TI - Density gradient multilayer polymerization for creating complex tissue. AB - An adaptable density gradient multilayer polymerization (DGMP) method facilitates simple fabrication of complex multicompartment scaffolds with structurally continuous interfaces. Solvent density liquid-liquid phase segregation compartmentalizes varied mechanical and chemical cues independently. Bulk photopolymerization produces stratified three-dimensional and two-dimensional matrices. Cells attach to patterned adhesion peptides on biomimetic 2D substrates. PMID- 22318772 TI - Disparities in periodontitis prevalence among chronic kidney disease patients. PMID- 22318774 TI - Quantitative analysis of perfumes in talcum powder by using headspace sorptive extraction. AB - Quantitative analysis of perfume dosage in talcum powder has been a challenge due to interference of the matrix and has so far not been widely reported. In this study, headspace sorptive extraction (HSSE) was validated as a solventless sample preparation method for the extraction and enrichment of perfume raw materials from talcum powder. Sample enrichment is performed on a thick film of poly(dimethylsiloxane) (PDMS) coated onto a magnetic stir bar incorporated in a glass jacket. Sampling is done by placing the PDMS stir bar in the headspace vial by using a holder. The stir bar is then thermally desorbed online with capillary gas chromatography-mass spectrometry. The HSSE method is based on the same principles as headspace solid-phase microextraction (HS-SPME). Nevertheless, a relatively larger amount of extracting phase is coated on the stir bar as compared to SPME. Sample amount and extraction time were optimized in this study. The method has shown good repeatability (with relative standard deviation no higher than 12.5%) and excellent linearity with correlation coefficients above 0.99 for all analytes. The method was also successfully applied in the quantitative analysis of talcum powder spiked with perfume at different dosages. PMID- 22318775 TI - Mastery Without Mystery: Why there is no Promethean Sin in Enhancement. AB - Several authors have suggested that we cannot fully grapple with the ethics of human enhancement unless we address neglected questions about our place in the world, questions that verge on theology but can be pursued independently of religion. A prominent example is Michael Sandel, who argues that the deepest objection to enhancement is that it expresses a Promethean drive to mastery which deprives us of openness to the unbidden and leaves us with nothing to affirm outside our own wills. Sandel's argument against enhancement has been criticized, but his claims about mastery and the unbidden, and their relation to religion, have not yet received sufficient attention. I argue that Sandel misunderstands the notions of mastery and the unbidden and their significance. Once these notions are properly understood, they have surprising implications. It turns out that the value of openness to the unbidden is not just independent of theism, as Sandel claims, but is in fact not even fully compatible with it. But in any case that value cannot support Sandel's objection to enhancement.This is because it is not enhancement but certain forms of opposition to enhancement that are most likely to express a pernicious drive to mastery. PMID- 22318776 TI - Minimal intervention concept: a new paradigm for operative dentistry. AB - The current treatment philosophy is to prevent and detect dental disease at the earliest stage in order to avoid invasive treatment. With the current understanding of the nature of dental disease and its process, the treatment philosophy is now changing to a more conservative approach and the concept of minimal intervention is gaining popularity in modern dentistry throughout the world. It is now established that demineralized but non-cavitated enamel and dentine can be healed and traditional surgical approach of drilling and filling may no longer be necessary as this only treats the symptoms of the disease and not the cause. However, when surgical intervention is indicated, the least invasive techniques such as preventive resin restoration and minimal cavity preparation are utilized. The aim of this article is to give dental professionals an overview of the concepts of minimal intervention dentistry and recent innovations in dental technology in both the diagnosis and treatment of dental caries. PMID- 22318777 TI - [HIV infection rates--an update]. PMID- 22318778 TI - Neisseria gonorrhoeae pilus attenuates cytokine response of human fallopian tube explants. AB - BACKGROUND: A role for pilus during attachment of Neisseria gonorrhoeae to epithelia of the female reproductive tract is currently assumed. However, Pil- gonococci have been observed during infection of the reproductive tract, which prompted us to examine the effect of pili on the dynamics of infection and the inflammatory responses of mucosal explants of the human fallopian tube. METHODS: Mucosal explants were infected in vitro with Opa negative Pil- and Pil+N. gonorrhoeae strains. RESULTS: Piliation enhanced gonococcal adherence to the epithelium within 3 h of infection (P < 0.05) but thereafter did not offer advantage to gonococci to colonize the epithelial cell surface (P > 0.05). No differences were found between the strains in numbers of gonococci inside epithelial cells. Pil- bacteria induced higher levels (P < 0.05) of IL-1beta, TNF alpha, GM-CSF, MCP-1, and MIP-1beta than Pil+ bacteria. There were no differences between both strains in LOS pattern, and Pil expression did not change after coincubation with mucosal strips. CONCLUSIONS: Results show that gonococcal invasion of the human fallopian tube can occur independently of pilus or Opa expression, and suggest that pilus, by inhibition of several key elements of the initial inflammatory response, facilitates sustained infection of this organ. PMID- 22318779 TI - New insight puts CRAF in sight as a therapeutic target. AB - By selectively depleting components of the RAF-MEK-ERK pathway in transgenic mice, it is now shown in 2 studies that CRAF is critical for signaling to MEK downstream of oncogenic Kras and that BRAF is not required. PMID- 22318780 TI - Comparison of 64-row and 16-row multidetector CT in the perfusion CT evaluation of acute ischemic stroke patients receiving intravenous thrombolytic therapy. AB - INTRODUCTION: Perfusion computed tomography (PCT) is increasingly performed in multimodal CT evaluation of acute ischemic stroke. We compared the technical quality of perfusion studies performed with a 16-row and a 64-row scanner and analyzed the differences between the scanners in their ability to detect perfusion defects. METHODS: We analyzed retrospectively the clinical and imaging data of 140 consecutive acute (<3 h) stroke patients who underwent multimodal CT evaluation and received intravenous rtPA. Alberta Stroke Program Early CT Score (ASPECTS) was assigned to PCT maps. Clinical and imaging parameters were compared between the two scanners. RESULTS: There were more motion artifacts in the 16-row studies (p = 0.04), and the analysis software was able to completely correct significantly fewer of these (p < 0.001). Both ASPECTS levels were optimally covered in only 29% of the 16-row studies, whereas in the 64-row studies, both levels were invariably optimally visualized (p < 0.001). This significantly decreased the sensitivity of the 16-row scanner to detect perfusion defects in the upper ASPECTS level (p = 0.02). The 64-row scanner was able to detect more perfusion defects that were located entirely outside the ASPECTS regions (p = 0.03). There was no significant difference in the 3-month functional outcome. CONCLUSIONS: The 16-row scanner suffered from limited anatomic coverage that decreased the sensitivity to detect perfusion defects in the cranial parts of the middle cerebral artery region. The 16-row studies had poorer technical quality that was in part attributable to higher sampling frequency and smaller slice thickness making the imaging more sensitive to small-scale movement of the patient. PMID- 22318781 TI - Pretreatment levels of peripheral neutrophils and lymphocytes as independent prognostic factors in patients with nasopharyngeal carcinoma. AB - BACKGROUND: The purpose of this study was to evaluate the counts and percentages of differential leukocytes as prognostic indicators in patients with nasopharyngeal carcinoma (NPC). METHODS: This study consisted of 1410 cases identified from an established prospective cohort of 1533 patients with NPC between October 2005 and October 2007 in the Sun Yat-Sen University Cancer Center. Multivariate Cox proportional hazards analyses were applied. RESULTS: A high percentage of lymphocyte was significantly associated with a favorable prognosis of NPC (highest vs lowest quartile, hazard ratio [HR], 95% confidence interval [CI] for overall and progression-free survival, HR, 0.71; 95% CI, 0.48 1.06; HR, 0.61; 95% CI, 0.43-0.86, respectively), whereas a high neutrophil percentage (HR, 1.62; 95% CI, 1.06-2.46; HR, 1.55; 95% CI, 1.10-2.18, respectively), and a neutrophil/lymphocyte ratio (NLR; HR, 1.57; 95% CI, 1.04 2.39; HR, 1.68; 95% CI, 1.19-2.38, respectively), were significantly related to a poor prognosis of NPC. CONCLUSION: Pretreatment NLR and percentages of lymphocyte and neutrophil are independent prognostic factors and may serve as clinically convenient and useful biomarkers for survival of patients with NPC. PMID- 22318782 TI - A phase I trial of S-1 with concurrent radiotherapy in patients with locally recurrent rectal cancer. AB - BACKGROUND: The purpose of this phase I trial of S-1 chemotherapy in combination with pelvic radiotherapy for locally recurrent rectal cancer was to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose-limiting toxicity (DLT) of S-1. METHODS: We enrolled 9 patients between April 2005 and March 2009. Radiotherapy (total dose, 60 Gy in 30 fractions) was given to the gross local recurrent tumor and pelvic nodal metastases using three-dimensional radiotherapy planning. We administered oral S-1 twice a day on days 1-14 and 22-35 during radiotherapy. The dose of S-1 was initially 60 mg/m(2)/day and was increased to determine the MTD and RD for this regimen. RESULTS: DLT appeared at dose level 2 (70 mg/m(2)/day) in 2 patients, who experienced grade 3 enterocolitis and consequently required suspension of S-1 administration for longer than 2 weeks. Hematological toxicity was mild and reversible. At the initial evaluation, complete regression and partial regression were seen in 1 patient (11%) and 2 patients (22%), respectively. CONCLUSION: This phase I trial of S-1 chemotherapy with pelvic radiotherapy for locally recurrent rectal cancer revealed that the MTD for S-1 was 70 mg/m(2)/day and the RD was 60 mg/m(2)/day. PMID- 22318783 TI - S100A8/A9 aggravates post-ischemic heart failure through activation of RAGE dependent NF-kappaB signaling. AB - The extracellular heterodimeric protein S100A8/A9 activates the innate immune system through activation of the receptor of advanced glycation end products (RAGE) and Toll-like receptors. As activation of RAGE has recently been associated with sustained myocardial inflammation and heart failure (HF) we studied the role of S100A8/A9 in the development of post-ischemic HF. Hypoxia led to sustained induction of S100A8/A9 accompanied by increased nuclear factor (NF )kappaB binding activity and increased expression of pro-inflammatory cytokines in cardiac fibroblasts and macrophages. Knockdown of either S100A8/A9 or RAGE rescued the induction of pro-inflammatory cytokines and NF-kappaB activation after hypoxia. In a murine model of post-ischemic HF both cardiac RNA and protein levels of S100A8/A9 were elevated as soon as 30 min after hypoxia with sustained activation up to 28 days after ischemic injury. Treatment with recombinant S100A8/A9 resulted in reduced cardiac performance following ischemia/reperfusion. Chimera experiments after bone marrow transplantation demonstrated the importance of RAGE expression on immune cells for their recruitment to the injured myocardium aggravating post-ischemic heart failure. Signaling studies in isolated ventricles indicated that MAP kinases JNK, ERK1/2 as well as NF-kappaB mediate signals downstream of S100A8/A9-RAGE in post-ischemic heart failure. Interestingly, cardiac performance was not affected by administration of S100A8/A9 in RAGE(-/-)-mice, which demonstrated significantly improved cardiac recovery compared to WT-mice. Our study provides evidence that sustained activation of S100A8/A9 critically contributes to the development of post ischemic HF driving the progressive course of HF through activation of RAGE. PMID- 22318784 TI - Energy expenditure in obstructive sleep apnea: validation of a multiple physiological sensor for determination of sleep and wake. AB - PURPOSE: Obstructive sleep apnea (OSA) may be associated with increased energy expenditure (EE) during sleep. As actigraphy is inaccurate at estimating EE from body movement counts alone, we aimed to compare a multiple physiological sensor with polysomnography for determination of sleep and wake, and to test the hypothesis that OSA is associated with increased EE during sleep. METHODS: We studied 50 adults referred for routine overnight polysomnography. In addition to polysomnography, the SenseWear Pro3 Armband(TM) (Bodymedia Inc.) was placed on the upper right arm. Epoch-by-epoch agreement rate between the measures of sleep versus wake was calculated. Linear regression analyses were performed for EE against apnea-hypopnea index (AHI), 3% oxygen desaturation index (ODI), body mass index (BMI), waist-hip ratio (WHR), gender, age, and average heart rate during sleep. RESULTS: The epoch-by-epoch agreement rate was high (79.9 +/- 1.6%) and the ability of the SenseWear to estimate sleep was very good (sensitivity, 88.7 +/- 1.5%). However, it was less accurate in determining wake (specificity 49.9 +/ 3.6%). Sleep EE was associated with AHI, 3% ODI, BMI, WHR, and male gender (p < 0.001 for all). Stepwise multiple linear regression however revealed that BMI, male gender, age, and average heart rate during sleep were independent predictors of EE (Model R (2) = 0.78). CONCLUSIONS: The SenseWear armband provides a reasonable estimation of sleep but a poor estimation of wake. Furthermore, in a selected population of OSA patients, increasing OSA severity is associated with increased EE during sleep, although primarily through an association with increased BMI. However, as our data are not adjusted for fat-free mass and the SenseWear has yet to be validated for EE in OSA patients, these data should be interpreted with caution. PMID- 22318786 TI - Management of acute paracetamol (acetaminophen) toxicity: a standardised proforma improves risk assessment and overall risk stratification by emergency medicine doctors. AB - BACKGROUND: Paracetamol (acetaminophen) poisoning is the most common toxicological presentation in the UK. Doctors managing patients with paracetamol poisoning need to assess the risk of their patient developing hepatotoxicity before determining appropriate treatment. Patients deemed to be at 'high risk' of hepatotoxicity have lower treatment thresholds than those deemed to be at 'normal risk'. Errors in this process can lead to harmful or potentially fatal under or over treatment. AIM: To determine how well treating doctors assess risk factor status and whether a standardised proforma is useful in the risk stratification process. METHODS: Retrospective 12-month case note review of all patients presenting with paracetamol poisoning to our large inner-city emergency department. Data were collected on the documentation of risk factors, the presence of a local hospital proforma and treatment outcomes. RESULTS: 249 presentations were analysed and only 59 (23.7%) had full documentation of all the risk factors required to make a complete risk assessment. 56 of the 59 (94.9%) had the local hospital proforma included in the notes; the remaining 3 (5.1%) had full documentation of risk factors despite the absence of a proforma. A local hospital proforma was more likely to be included in the emergency department notes in those with 'adequate documentation' (78 out of 120 (65%)) than for those with 'inadequate documentation' (16 out of 129 (12.4%)); X(2), p<0.001. CONCLUSIONS: Despite a low overall uptake of the proforma, use of a standardised proforma significantly increased the likelihood of documentation of the risk factors which increase risk for hepatotoxicity following paracetamol poisoning. PMID- 22318787 TI - The formation of furfural compounds in selected saccharide- and polysaccharide based pharmaceutical excipients. AB - The acid hydrolysis of various selected saccharide- and polysaccharide-based pharmaceutical excipients under acid hydrolysis and the formation of degradation compounds were studied. New degradation products formed from these excipients were discovered. Liquid chromatography-mass spectrometry and nuclear magnetic resonance techniques were employed to identify and fully characterize these unknown compounds. The degradation products were identified as [(5-formylfuran-2 yl)methoxy]acetic acid, 5-[(propan-2-yloxy)methyl]furan-2-carbaldehyde, along with the previously identified 5-(methoxymethyl)furan-2-carbaldehyde. On the basis of the identification of these degradation products, a reasonable mechanism for their formation can be proposed. Temperature and pH affect the hydrolysis rates of saccharides and polysaccharides, which in turn affects the rate of formation of furfural compounds. PMID- 22318788 TI - Experience, perception, and depression. PMID- 22318789 TI - ADHD pharmacotherapy: rates of stimulant use and cardiovascular risk. PMID- 22318790 TI - Advances in the genetics of ADHD. PMID- 22318791 TI - Cognitive bias modification: an intervention approach worth attending to. PMID- 22318792 TI - Antidepressant treatment during pregnancy. PMID- 22318793 TI - John Cade. PMID- 22318794 TI - Abnormal thyroid function tests in psychiatric patients: a red herring? AB - Thyroid abnormalities can induce mood, anxiety, psychotic, and cognitive disorders. Thus, thyroid function tests are routinely checked in psychiatric patients. However, up to one-third of psychiatric patients may demonstrate thyroid function test abnormalities that do not reflect true thyroid disease, but rather are a manifestation of secondary effects on one or more levels of the hypothalamic-pituitary-thyroid (HPT) axis. Originally termed the euthyroid sick syndrome, this phenomenon is now more commonly referred to as "non-thyroidal illness." In psychiatric patients with non-thyroidal illness, patterns of thyroid function test abnormalities may vary considerably based upon factors such as the underlying psychiatric disorder, the presence of substance abuse, or even the use of certain psychiatric medications. Thus, any abnormal thyroid function tests in psychiatric patients should be viewed with skepticism. Given the fact that thyroid function test abnormalities seen in non-thyroidal illness usually resolve spontaneously, treatment is generally unnecessary, and may even be potentially harmful. PMID- 22318795 TI - Methylphenidate and risk of serious cardiovascular events in adults. AB - OBJECTIVE: The authors sought to determine whether use of methylphenidate in adults is associated with elevated rates of serious cardiovascular events compared with rates in nonusers. METHOD: This was a cohort study of new users of methylphenidate based on administrative data from a five-state Medicaid database and a 14-state commercial insurance database. All new methylphenidate users with at least 180 days of prior enrollment were identified. Users were matched on data source, state, sex, and age to as many as four comparison subjects who did not use methylphenidate, amphetamines, or atomoxetine. A total of 43,999 new methylphenidate users were identified and matched to 175,955 nonusers. Events of primary interest were 1) sudden death or ventricular arrhythmia, 2) stroke, 3) myocardial infarction, and 4) a composite endpoint of stroke or myocardial infarction. RESULTS: The age-standardized incidence rate per 1,000 person-years of sudden death or ventricular arrhythmia was 2.17 (95% CI=1.63-2.83) in methylphenidate users and 0.98 (95% CI=0.89-1.08) in nonusers, for an adjusted hazard ratio of 1.84 (95% CI=1.33-2.55). Dosage was inversely associated with risk. Adjusted hazard ratios for stroke, myocardial infarction, and the composite endpoint of stroke or myocardial infarction did not differ statistically from 1. CONCLUSIONS: Although initiation of methylphenidate was associated with a 1.8 fold increase in risk of sudden death or ventricular arrhythmia, the lack of a dose-response relationship suggests that this association may not be a causal one. PMID- 22318796 TI - The impact of internet coverage of the March 2011 Japan earthquake on sleep and posttraumatic stress symptoms: an international perspective. PMID- 22318797 TI - Conceptual issues in psychiatric gene-environment interaction research. PMID- 22318807 TI - Linear self-assembly of nanoparticles within liquid crystal defect arrays. AB - In the presence of oriented smectic liquid crystal defects, hybrid systems of nanoparticles/liquid crystals form straight chains of nanoparticles of length longer than tens of micrometers and width equal to one single nanoparticle. The interparticle distance in a chain can be varied between a few micrometers and 1.5 nm, highlighting the control of optical absorption by light polarization monitored by gold nanoparticle concentration. PMID- 22318808 TI - Automated analysis of lidocaine and its metabolite in plasma by in-tube solid phase microextraction coupled with LC-UV for pharmacokinetic study. AB - A sensitive, selective, and reproducible in-tube solid-phase microextraction and liquid chromatographic (in-tube SPME/LC-UV) method for determination of lidocaine and its metabolite monoethylglycinexylidide (MEGX) in human plasma has been developed, validated, and further applied to pharmacokinetic study in pregnant women with gestational diabetes mellitus (GDM) subjected to epidural anesthesia. Important factors in the optimization of in-tube SPME performance are discussed, including the draw/eject sample volume, draw/eject cycle number, draw/eject flow rate, sample pH, and influence of plasma proteins. The limits of quantification of the in-tube SPME/LC method were 50 ng/mL for both metabolite and lidocaine. The interday and intraday precision had coefficients of variation lower than 8%, and accuracy ranged from 95 to 117%. The response of the in-tube SPME/LC method for analytes was linear over a dynamic range from 50 to 5000 ng/mL, with correlation coefficients higher than 0.9976. The developed in-tube SPME/LC method was successfully used to analyze lidocaine and its metabolite in plasma samples from pregnant women with GDM subjected to epidural anesthesia for pharmacokinetic study. PMID- 22318809 TI - Autophagy in innate recognition of pathogens and adaptive immunity. AB - Autophagy is a specialized cellular pathway involved in maintaining homeostasis by degrading long-lived cellular proteins and organelles. Recent studies have demonstrated that autophagy is utilized by immune systems to protect host cells from invading pathogens and regulate uncontrolled immune responses. During pathogen recognition, induction of autophagy by pattern recognition receptors leads to the promotion or inhibition of consequent signaling pathways. Furthermore, autophagy plays a role in the delivery of pathogen signatures in order to promote the recognition thereof by pattern recognition receptors. In addition to innate recognition, autophagy has been shown to facilitate MHC class II presentation of intracellular antigens to activate CD4 T cells. In this review, we describe the roles of autophagy in innate recognition of pathogens and adaptive immunity, such as antigen presentation, as well as the clinical relevance of autophagy in the treatment of human diseases. PMID- 22318810 TI - Current management and future strategies of gastric cancer. AB - The overall prognosis of gastric cancer has gradually improved over the past decades with growing awareness of potential carcinogens, surveillance programs and early diagnosis, as well as advances in surgical techniques and multimodality treatments. Nevertheless, the outcome of advanced stage disease still remains poor with currently available treatments, and a worldwide consensus on the standard management thereof has not been established. To improve prognosis and quality of life in gastric cancer patients, both standardization and individualization of managements are imperative. Diagnostic tests and surgical procedures need to be further sophisticated and standardized based on more recent evidences from ongoing and future randomized controlled trials, while comprehensive management should be individualized to each patient. Future challenges lie with how to optimize personalized therapies by deciphering biological complexity of gastric cancer and incorporating molecular biomarkers in clinical practice to forecast prognosis and to guide targeted therapeutics in adjunct to current standards of care. PMID- 22318811 TI - Role of inflammation in the pathogenesis of arterial stiffness. AB - Increased arterial stiffness is an independent predictor of cardiovascular disease independent from blood pressure. Recent studies have shed new light on the importance of inflammation on the pathogenesis of arterial stiffness. Arterial stiffness is associated with the increased activity of angiotensin II, which results in increased NADPH oxidase activity, reduced NO bioavailability and increased production of reactive oxygen species. Angiotensin II signaling activates matrix metalloproteinases (MMPs) which degrade TGFbeta precursors to produce active TGFbeta, which then results in increased arterial fibrosis. Angiotensin II signaling also activates cytokines, including monocyte chemoattractant protein-1, TNF-alpha, interleukin-1, interleukin-17 and interleukin- 6. There is also ample clinical evidence that demonstrates the association of inflammation with increased arterial stiffness. Recent studies have shown that reductions in inflammation can reduce arterial stiffness. In patients with rheumatoid arthritis, increased aortic pulse wave velocity in patients was significantly reduced by anti tumor necrosis factor-alpha therapy. Among the major classes of anti hypertensive drugs, drugs that block the activation of the RAS system may be more effective in reducing the progression of arterial stiffness. Thus, there is rationale for targeting specific inflammatory pathways involved in arterial stiffness in the development of future drugs. Understanding the role of inflammation in the pathogenesis of arterial stiffness is important to understanding the complex puzzle that is the pathophysiology of arterial stiffening and may be important for future development of novel treatments. PMID- 22318812 TI - Kawasaki disease: laboratory findings and an immunopathogenesis on the premise of a "protein homeostasis system". AB - Kawasaki disease (KD) is a self-limited systemic inflammatory illness, and coronary artery lesions (CALs) are a major complication determining the prognosis of the disease. Epidemiologic studies in Asian children suggest that the etiologic agent(s) of KD may be associated with environmental changes. Laboratory findings are useful for the diagnosis of incomplete KD, and they can guide the next-step in treatment of initial intravenous immunoglobulin non-responders. CALs seem to develop in the early stages of the disease before a peak in inflammation. Therefore early treatment, before the peak in inflammation, is mandatory to reduce the risk of CAL progression and severity of CALs. The immunopathogenesis of KD is more likely that of acute rheumatic fever than scarlet fever. A hypothetical pathogenesis of KD is proposed under the premise of a "protein homeostasis system"; where innate and adaptive immune cells control pathogenic proteins that are toxic to host cells at a molecular level. After an infection of unknown KD pathogen(s), the pathogenic proteins produced from an unknown focus, spread and bind to endothelial cells of coronary arteries as main target cells. To control the action of pathogenic proteins and/or substances from the injured cells, immune cells are activated. Initially, non-specific T cells and non specific antibodies are involved in this reaction, while hyperactivated immune cells produce various cytokines, leading to a cytokine imbalance associated with further endothelial cell injury. After the emergence of specific T cells and specific antibodies against the pathogenic proteins, tissue injury ceases and a repair reaction begins with the immune cells. PMID- 22318813 TI - Sequential involvement of the nervous system in subacute combined degeneration. AB - PURPOSE: Subacute combined degeneration (SCD) involves progressive degeneration of the spinal cord, optic nerve, and peripheral nerves. Vitamin B12 (VB12) is a co-factor in myelin synthesis. Because each cell that constitutes the myelin component in the central nervous system and peripheral nervous system is different, it is improbable that these cells undergo simultaneous degeneration. However, the sequence of degeneration in SCD has not been established. MATERIALS AND METHODS: In this study, we analysed medical records and electrophysiological data of patients who showed neurological symptoms and whose serum VB12 levels were lower than 200 pg/mL. RESULTS: We enrolled 49 patients in this study. Their mean VB12 level was 68.3 pg/mL. Somatosensory evoked potential (SEP) study showed abnormal findings in 38 patients. Of the 40 patients who underwent visual evoked potential (VEP) study, 14 showed abnormal responses. Eighteen patients showed abnormal findings on a nerve conduction study (NCS). In this study, abnormal posterior tibial nerve SEPs only were seen in 16 patients, median nerve SEPs only were seen in 3 patients, abnormal VEPs only in two, and abnormal NCS responses in one patient. No patient complained of cognitive symptoms. CONCLUSION: In SCD, degeneration appears to progress in the following order: lower spinal cord, cervical spinal cord, peripheral nerve/optic nerve, and finally, the brain. PMID- 22318814 TI - Electroanatomical characteristics of idiopathic left ventricular tachycardia and optimal ablation target during sinus rhythm: significance of preferential conduction through Purkinje fibers. AB - PURPOSE: We hypothesized that Purkinje potential and their preferential conduction to the left ventricle (LV) posteroseptum during sinus rhythm (SR) are part of reentrant circuits of idiopathic left ventricular tachycardia (ILVT) and reentry anchors to papillary muscle. MATERIALS AND METHODS: In 14 patients with ILVT (11 men, mean age 31.5+/-11.1 years), we compared Purkinje potential and preferential conduction during SR with VT by non-contact mapping (NCM). If clear Purkinje potential(SR) was observed in the LV posteroseptum and the earliest activation site (EA) of preferential conduction at SR (EA(SR)) was well matched with that of VT (EA(VT)), EA(SR) was targeted for radiofrequency catheter ablation (RFCA). Also, the anatomical locations of successful ablation sites were evaluated by echocardiography in five additional patients. RESULTS: 1) All induced VTs exhibited clear Purkinje potential(VT) and preferential conduction in the LV posteroseptum. The Purkinje potential(VT) and EA(VT) was within 5.8+/-8.2 mm of EA(SR). However, the breakout sites of VT were separated by 30.2+/-12.6 mm from EA(VT) to the apical side. 2) Purkinje potential(SR) demonstrated a reversed polarity to Purkinje potential(VT), and the interval of Purkinje potential(SR) QRS was longer than the interval of Purkinje potential(VT)-QRS (p<0.02) 3) RFCA targeting EA(SR) eliminated VT in all patients without recurrence within 23.3+/ 7.5 months, and the successful ablation site was discovered at the base of papillary muscle in the five additional (100%) patients. CONCLUSION: NCM-guided localization of EA(SR) with Purkinje potential(SR) matches well with EA(VT) with Purkinje potential(VT) and provides an effective target for RFCA, potentially at the base of papillary muscle in patients with ILVT. PMID- 22318815 TI - The influence of exogenous fat and water on lumbar spine bone mineral density in healthy volunteers. AB - PURPOSE: Changes in human body composition can affect the accuracy of spine bone mineral density (BMD) measurements. The purpose of this study was to evaluate whether fat and water in the soft tissue of the abdomen influence lumbar spine BMD measurements obtained using dual energy X-ray absorptiometry (DXA). MATERIALS AND METHODS: Duplicate BMD measurements were carried out on healthy volunteers (10 men and 10 women) and the Hologic anthropomorphic spine phantom had on the same day before and after placement of following 3 materials in the abdominal area: lard 900 g, 1.5 cm thick; oil 1.4 liters in a vinyl bag; and water 1.2 liters in a vinyl bag. RESULTS: In the case of human participants, following the placement of exogenous water to mimic extracellular fluid (ECF), there was a significant decrease in lumbar spine BMD (-0.012 g/cm2, p=0.006), whereas the placement of exogenous lard and oil to mimic abdominal fat produced a slight increase in lumbar spine BMD (0.006 g/cm2, p=0.301; 0.008 g/cm2, p=0.250, respectively). The average percentage of lumbar spine BMD change with and without exogenous lard, oil, and water showed increase of 0.51%, and 0.67%, and decrease of 1.02%, respectively. Using the phantom, BMD decreased with the placement of both lard (-0.002 g/cm2, p=0.699) and water (-0.006 g/cm2, p=0.153); however, there was no difference in BMD after oil placement. CONCLUSION: These results suggest that in cases where changes in fat and ECF volume are similar, ECF exerts a greater influence than fat on DXA lumbar BMD measurements. PMID- 22318816 TI - Effects of N-acetylcysteine on nicotinamide dinucleotide phosphate oxidase activation and antioxidant status in heart, lung, liver and kidney in streptozotocin-induced diabetic rats. AB - PURPOSE: Hyperglycemia increases reactive oxygen species (ROS) and the resulting oxidative stress plays a key role in the pathogenesis of diabetic complications. Nicotinamide dinucleotide phosphate (NADPH) oxidase is one of the major sources of ROS production in diabetes. We, therefore, examined the possibility that NADPH oxidase activation is increased in various tissues, and that the antioxidant N acetylcysteine (NAC) may have tissue specific effects on NADPH oxidase and tissue antioxidant status in diabetes. MATERIALS AND METHODS: Control (C) and streptozotocin-induced diabetic (D) rats were treated either with NAC (1.5 g/kg/day) orally or placebo for 4 weeks. The plasma, heart, lung, liver, kidney were harvested immediately and stored for biochemical or immunoblot analysis. RESULTS: levels of free 15-F(2t)-isoprostane were increased in plasma, heart, lung, liver and kidney tissues in diabetic rats, accompanied with significantly increased membrane translocation of the NADPH oxidase subunit p67phox in all tissues and increased expression of the membrane-bound subunit p22phox in heart, lung and kidney. The tissue antioxidant activity in lung, liver and kidney was decreased in diabetic rats, while it was increased in heart tissue. NAC reduced the expression of p22phox and p67phox, suppressed p67phox membrane translocation, and reduced free 15-F(2t)-isoprostane levels in all tissues. NAC increased antioxidant activity in liver and lung, but did not significantly affect antioxidant activity in heart and kidney. CONCLUSION: The current study shows that NAC inhibits NADPH oxidase activation in diabetes and attenuates tissue oxidative damage in all organs, even though its effects on antioxidant activity are tissue specific. PMID- 22318817 TI - The box simulator is useful for training novice endoscopists in basic endoscopic techniques. AB - PURPOSE: The present study was aimed at evaluating the usefulness of box simulators for training novice endoscopists. MATERIALS AND METHODS: An explanation of the goals, contents, and features of the simulator was given to study participants. The participants then received "hands-on training" in gastrointestinal endoscopy techniques using a box simulator. Subsequently, they were asked to answer 19 structured questions about the simulator. Ratings were scored on a scale from 1 to 5 for questions concerning their first impression of the simulator. Questions on the usefulness of the simulator and the training course were answered as "agree", "disagree", or "no opinion". RESULTS: A total of 32 participants filled out the questionnaire. The mean scores on the simulator's usefulness, features, and realistic movements before the training were between 1.5 and 2.0. There were no significant differences between the mean values of the scores given by novice users compared to non-novice users. However, after receiving training on the simulator, 90.6% of the participants considered the box simulator a generally useful tool for learning basic endoscopic techniques, and 90.6% agreed that the simulator was useful for improving hand-eye coordination. CONCLUSION: Box simulators may be useful for training novice endoscopists in basic gastrointestinal endoscopic techniques. PMID- 22318818 TI - Endoscopist specialty is associated with high-quality endoscopy in Korea. AB - PURPOSE: The present study was aimed to determine whether endoscopist specialty is associated with high-quality endoscopy. MATERIALS AND METHODS: We prospectively collected endoscopy quality related data based on the Endoscopy Quality Rating Scale (EQRS) of 277 endoscopy units in a hospital setting from the National Cancer Screening Program of Korea in 2009. Gastroenterology medical professors (n=154) from university hospitals visited each endoscopy unit and graded the unit according to the EQRS. The scores from the EQRS were analyzed and compared in relation to endoscopy training during residency and endoscopy subspecialist certification. RESULTS: After excluding data from 3 endoscopy units, EQRS data from 274 endoscopy units were analyzed: 263 esophagogastroduodenoscopy (EGD) screening units and 90 colonoscopy screening units. There were no significant differences in the scores of EQRS with respect to endoscopy training during residency (p=no significance), except for scores of EGDs for "Facility and Equipment" (p=0.030). However, EQRS scores were significantly higher in the endoscopy units where endoscopy subspecialists performed the endoscopies than those where Endoscopy Subspecialists did not perform the endoscopies (p<0.05, except p=0.08 for the "Process" criteria of EGD). CONCLUSION: Endoscopist specialty is an important determinant of high quality endoscopy in Korea. PMID- 22318819 TI - Acute variceal hemorrhage in patients with liver cirrhosis: weekend versus weekday admissions. AB - PURPOSE: Little is known about the impact of weekend admission on acute variceal hemorrhage (AVH). Thus, we investigated whether day of admission due to AVH influenced in-hospital mortality. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 294 patients with cirrhosis admitted between January 2005 and February 2009 for the management of AVH. Clinical characteristics were compared between patients with weekend and weekday admission, and independent risk factors for in-hospital mortality were determined by multivariate binary logistic regression analysis. RESULTS: No demographic differences were observed between patients according to admission day or in the clinical course during hospitalization. Seventeen (23.0%) of 74 patients with weekend admission and 48 (21.8%) of 220 with weekday admission died during hospitalization (p=0.872). Univariate and subsequent multivariate analysis showed that initial presentation with hematochezia [p=0.042; hazard ratio (HR), 2.605; 95% confidence interval (CI), 1.038-6.541], in-patient status at the time of bleeding (p=0.003; HR, 4.084; 95% CI, 1.598-10.435), Child-Pugh score (p<0.001; HR, 1.877; 95% CI, 1.516-2.324), and number of endoscopy sessions for complete hemostasis (p=0.001; HR, 3.864; 95% CI, 1.802-8.288) were independent predictors for in-hospital mortality. CONCLUSION: Weekend admission did not influence in hospital mortality in patients with cirrhosis who presented AVH. PMID- 22318820 TI - Spontaneous bacterial peritonitis in patients with hepatitis B virus-related liver cirrhosis: community-acquired versus nosocomial. AB - PURPOSE: Spontaneous bacterial peritonitis (SBP) frequently develops in patients with liver cirrhosis; however, there is little data to suggest whether the acquisition site of infection influences the prognosis. This study compared the bacteriology, clinical characteristics and treatment outcomes of community acquired SBP (CA-SBP) and nosocomial SBP (N-SBP). MATERIALS AND METHODS: The medical records of 130 patients with hepatitis B virus (HBV)-related liver cirrhosis, who had experienced a first episode of SBP between January 1999 and December 2008, were reviewed. RESULTS: The study population included 111 (85.4%) patients with CA-SBP and 19 (14.6%) patients with N-SBP. Baseline and microbiological characteristics as well as clinical course, including in-hospital mortality, did not differ between patients with CA-SBP and those with N-SBP (all p>0.05). The median survival time was 6.5 months, and 117 (90.0%) patients died during the follow-up period. Patients with CA-SBP and N-SBP survived for median periods of 6.6 and 6.2 months, respectively, without significant difference (p=0.569). Time to recurrence did not differ between patients with CA-SBP and N SBP (4.7 vs. 3.6 months, p=0.925). CONCLUSION: The acquisition site of infection did not affect clinical outcomes for patients with HBV-related liver cirrhosis who had experienced their first episode of SBP. Third-generation cephalosporins may be effective in empirically treating these patients, regardless of the acquisition site of the infection. PMID- 22318821 TI - How many valid measurements are necessary to assess liver fibrosis using FibroScan(r) in patients with chronic viral hepatitis? An analysis of subjects with at least 10 valid measurements. AB - PURPOSE: Using FibroScan(r) to obtain a reliable liver stiffness measurement (LSM) may require more than 10 valid measurements (VMs), according to the manufacturer's recommendations. However, this requirement lacks scientific evidence in support thereof. We investigated the minimal number of VMs required to assess liver fibrosis without significant loss of accuracy in patients with chronic hepatitis B (CHB) and C (CHC) and predictors of discordance between LSM and liver biopsy (LB). MATERIALS AND METHODS: Between January 2005 and December 2009, we prospectively enrolled 182 patients with CHB and 68 patients with CHC who were to undergo LB and LSM before starting antiviral treatment. Only LSMs with at least 10 VMs were considered reliable. The Batts and Ludwig scoring system was used for histologic assessment. RESULTS: The mean age and body mass index were 46.0 years and 23.4 kg/m2 in patients with CHB and 49.7 years and 23.1 kg/m2 in those with CHC, respectively. The median elasticity scores from the first 3, first 5, and all VMs taken significantly predicted fibrosis stages >=F2 and F4 (all p<0.05) without significant differences (all p>0.05 by DeLong's method). Alanine aminotransferase (ALT) was the only predictor of discordance in fibrosis stage as estimated by the median elasticity score from the first 3 VMs and by LB in patients with CHB, whereas no significant predictor was identified in those with CHC. CONCLUSION: After comparison of patients who had more than 10 valid measurements for LSM, three VMs may be enough to assess liver fibrosis using LSM without significant loss of accuracy in patients with CHC and patients with CHB. However, ALT should be considered when interpreting LSM for patients with CHB. PMID- 22318822 TI - Berberine inhibited the growth of thyroid cancer cell lines 8505C and TPC1. AB - PURPOSE: Thyroid cancer is the most common malignancy in Korean females and can be treated with good prognosis. However, drugs to treat aggressive types of thyroid cancer such as poorly differentiated or anaplastic thyroid cancer have not yet been established. To that end, we analyzed the effects of berberine on human thyroid cancer cell lines to determine whether this compound is useful in the treatment of aggressive thyroid cancer. MATERIALS AND METHODS: The two thyroid cancer cell lines 8505C and TPC1, under adherent culture conditions, were treated with berberine and analyzed for changes in cell growth, cell cycle duration, and degree of apoptosis. RESULTS: Following berberine treatment, both cell lines showed a dose-dependent reduction in growth rate. 8505C cells showed significantly increased levels of apoptosis following berberine treatment, whereas TPC1 cells showed cell cycle arrest at the G0/G1 phase. Immunobloting of p-27 expression following berberine treatment showed that berberine induced a little up-regulation of p-27 in 8505c cells but relatively high up-regulation of p-27 in TPC1 cells. CONCLUSION: These results suggest that berberine treatment of thyroid cancer can inhibit proliferation through apoptosis and/or cell cycle arrest. Thus, berberine may be a novel anticancer drug for the treatment of poorly differentiated or anaplastic thyroid cancer. PMID- 22318823 TI - Treatment outcome of patients with anaplastic thyroid cancer: a single center experience. AB - PURPOSE: Anaplastic thyroid cancer is known to have a poor prognosis due to its aggressive and rapid metastasis with median survival of less than 6 months. Multimodal treatment involving surgery and chemoradiotherapy has been used to improve the survival of patients. Here, we retrospectively review of treatment outcome of 13 consecutive patients who were treated at a single center. MATERIALS AND METHODS: We retrospectively reviewed medical records of 13 anaplastic thyroid cancer patients who received multidisciplinary treatment between 2006 and 2010. Kaplan-Meier survival curve was used to analyze progression-free survival and overall survival of patients. RESULTS: The median patient age at diagnosis was 69 years, and six patients had stage IVc diseases. Eight patients received primary surgery followed by radiotherapy or concurrent chemoradiotherapy (CCRT). Five patients received weekly doxorubicin-based definitive CCRT, but only one patient's condition remained stable, while the rest experienced rapid disease progression. The median progression-free survival was 2.8 months (95% CI, 1.2-4.4 months), and the median overall survival was 3.8 months (95% CI, 3.0-4.6 months). CONCLUSION: Patients with anaplastic thyroid cancer showed poor prognosis despite multimodality treatment. Therefore, identification of novel therapeutic targets is warranted to take an effective mode of treatment. PMID- 22318824 TI - Are clinically insignificant prostate cancers really insignificant among Korean men? AB - PURPOSE: We aimed to determine whether 12 core-extended biopsies of the prostate could predict insignificant prostate cancer (IPCa) in Koreans reliably enough to recommend active surveillance. MATERIALS AND METHODS: Two hundred and ninety seven patients who underwent radical prostatectomy after 12 core-extended prostate biopsies were retrospectively reviewed. 38 cases (12.8%) were shown to be IPCa. RESULTS: The average age was 65.2 years, serum PSA was 5.49 ng/dL, and the PSA density was 0.11. The Gleason scores (GS) were 6 (3+3) in 31, 5 (3+2) in 4, and 4 (2+2) in 3. After radical prostatectomy, higher GS was given in 16 (42.1%), whereas lower GS was given in 1 case (2.6%), as compared with the GS obtained from biopsy. 11 (28.9%) had GS of 7 (3+4) and 5 (13.2%) had GS of 7 (4+3). 6 in GS 7 (4+3) and 1 in GS 7 (3+4) showed prostate capsule invasion and 1 in GS 7 (4+3) had seminal vesicle invasion. Prostate capsule invasion was observed in 1 with GS 6 (3+3). The rate of inaccuracy of the contemporary Epstein criteria was 42.1%. Only PSA density was a reliable indicator of clinically IPCa (odds ratio=1.384, 95% CI, 1.103 to 2.091). CONCLUSION: Diagnosis of IPCa from a prostate biopsy underestimated the true nature of prostate cancer in as many as 42.1% of Koreans. PMID- 22318825 TI - Application of a new spirometric reference equation and its impact on the staging of Korean chronic obstructive pulmonary disease patients. AB - PURPOSE: A new spirometric reference equation was recently developed from the first national chronic obstructive pulmonary disease (COPD) survey in Korea. However, Morris' equation has been preferred for evaluating spirometric values instead. The objective of this study was to evaluate changes in severity staging in Korean COPD patients by adopting the newly developed Korean equation. MATERIALS AND METHODS: We evaluated the spirometric data of 441 COPD patients. The presence of airflow limitation was defined as an observed post-bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) less than 0.7, and the severity of airflow limitation was assessed according to GOLD stages. Spirometric values were reassessed using the new Korean equation, Morris' equation and other reference equations. RESULTS: The severity of airflow limitation was differently graded in 143 (32.4%) patients after application of the new Korean equation when compared with Morris' equation. All 143 patients were reallocated into more severe stages (49 at mild stage, 65 at moderate stage, and 29 at severe stage were changed to moderate, severe and very severe stages, respectively). Stages according to other reference equations were changed in 18.6 49.4% of the patients. CONCLUSION: These results indicate that equations from different ethnic groups do not sufficiently reflect the airflow limitation of Korean COPD patients. The Korean reference equation should be used for Korean COPD patients in order to administer proper treatment. PMID- 22318826 TI - Serum vascular endothelial growth factor and angiopoietin-2 are associated with the severity of systemic inflammation rather than the presence of hemoptysis in patients with inflammatory lung disease. AB - PURPOSE: Vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) are major mediators of angiogenesis and are induced by tissue inflammation and hypoxia. The purpose of this study was to investigate whether serum VEGF and Ang 2 are associated with the presence of hemoptysis and the extent of systemic inflammation in patients with inflammatory lung diseases. MATERIALS AND METHODS: We prospectively enrolled 52 patients with inflammatory lung disease between June 2008 and October 2009. RESULTS: The median values of VEGF and Ang-2 were 436 pg/mL and 2383 pg/mL, respectively. There was a significant positive correlation between serum Ang-2 and VEGF levels. VEGF levels were not significantly different according to the presence of hemoptysis. C-reactive protein (CRP) and Ang-2 level were significantly higher in patients without hemoptysis (n=26) than in those with hemoptysis (n=26; p<0.001 and p<0.001, respectively). CRP and arterial oxygen tension (PaO2) were significantly correlated with both serum VEGF (p=0.032 and p=0.016, respectively) and Ang-2 levels (p<0.001 and p=0.041, respectively), after adjusting for other factors. Age and the absence of hemoptysis were factors correlated with serum Ang-2 levels. CONCLUSION: Our study suggests that serum VEGF and Ang-2 levels are associated with PaO2 and the severity of inflammation rather than the presence of hemoptysis in patients with inflammatory lung diseases. Thus, hemoptysis may not be mediated by increased serum levels of VEGF and Ang-2 in patients with inflammatory lung diseases, and further studies are required to determine the mechanisms of hemoptysis. PMID- 22318827 TI - CpG array analysis of histone H3 lysine 4 trimethylation by chromatin immunoprecipitation linked to microarrays analysis in peripheral blood mononuclear cells of IgA nephropathy patients. AB - PURPOSE: The purpose of the present study was to investigate the aberrance of histone H3 lysine 4 trimethylation (H3K4me3) in patients with IgA Nephropathy (IgAN). MATERIALS AND METHODS: In this study, H3K4me3 variations in peripheral blood mononuclear cells (PBMCs) from 15 IgAN patients and 15 healthy subjects were analyzed using chromatin immunoprecipitation linked to microarrays analysis (ChIP-chip). ChIP real-time PCR was used to validate the microarray results. Expression analysis by quantitative real-time PCR (qRT-PCR) revealed correlations between mRNA and H3K4me3 levels. DNA methylation status was analyzed by quantitative methylation-specific PCR. RESULTS: We found that 321 probes displayed significant H3K4me3 differences in IgAN patients compared with healthy controls. Among these probes, 154 probes displayed increased H3K4me3 and 167 probes demonstrated decreased H3K4me3. For further validation, we selected 4 key relevant genes (FCRL4, GALK2, PTPRN2 and IL1RAPL1) to study. The results of ChIP real-time PCR coincided well with the microarray data. Quantitative RT-PCR revealed the correlations between the mRNA expression and the methylation levels of H3K4me3. Different degrees of DNA methylation alterations appeared on the selected positive genes. CONCLUSION: Our studies indicated that there were significant alterations in H3K4me3 in IgAN patients. These findings may help to explain the disturbed immunity and abnormal glycosylation involved in IgAN patients. PMID- 22318828 TI - Hydrodynamic relationship between color Doppler ultrasonography findings and the number of internal spermatic veins in varicoceles. AB - PURPOSE: The improvement of testicular volume, testosterone levels and sperm concentration was suggested to be significantly associated with the number of internal spermatic veins (ISVs) ligated during varicocelectomy. Herein, we investigated preoperative color Doppler ultrasonography (CDU) findings as potential preoperative predictors of the number of ISVs requiring ligation during microsurgical subinguinal varicocelectomy. MATERIALS AND METHODS: In a prospective evaluation of 40 patients, maximal vein size and maximal reflux velocity were measured, while the total cross-sectional area of the affected testicular veins during a Valsalva maneuver was calculated using CDU by a single uroradiologist. Microsurgical subinguinal varicocelectomies were performed by one urologist. RESULTS: Among the semen parameters, semen morphology showed significant improvement (p=0.033), which was much clearer in the patients with a higher number of ISVs ligated than a lower number of ISVs ligated. Among the various preoperative variables, maximal reflux velocity and total cross-sectional area on CDU were related to the number of ISVs ligated (r=-0.442, p=0.004; r=0.594, p=0.000, respectively). Furthermore, univariate and multivariate linear regression analyses showed that maximal reflux velocity and total cross-sectional area on CDU were independent predictive factors of the number of ISVs ligated. CONCLUSION: Maximal reflux velocity and total cross-sectional area on CDU were related to the number of ISVs ligated. This means that the maximal reflux velocity and total cross-sectional area measured by preoperative CDU can predict the number of ISVs requiring ligation during microsurgical subinguinal varicocelectomy, which might be related to significant improvement of semen parameters after varicocelectomy. PMID- 22318829 TI - Cytomegalovirus infection according to cell source after hematopoietic cell transplantation in pediatric patients. AB - PURPOSE: This study was performed in order to evaluate the incidence and characteristics of cytomegalovirus (CMV) infection in children with acute leukemia according to donor source and graft type. MATERIALS AND METHODS: We retrospectively identified children with acute leukemia who had received allogeneic hematopoietic cell transplantation at Samsung Medical Center in Korea from October 1998 to December 2009. RESULTS: In total, 134 recipients were identified. The patients were classified into the following three groups: unrelated cord blood (CB, n=36), related bone marrow or peripheral blood stem cells (RD, n=41), and unrelated bone marrow or peripheral blood stem cells (UD, n=57). The 365-day cumulative incidence of CMV antigenemia was not significantly different among the three groups (CB 67% vs. RD 49% vs. UD 65%, p=0.17). However, CB recipients had the highest median value of peak antigenemia (CB 160/2*105 leukocytes vs. RD 7/2*105 leukocytes vs. UD 19/2*105 leukocytes, p<0.01) and the longest duration of CMV antigenemia than the other stem cell source recipients (CB 87 days vs. RD 17 days vs. UD 28 days, p<0.01). In addition, the 730-day cumulative incidence of CMV disease was the highest in the CB recipients (CB 36% vs. RD 2% vs. UD 5%, p<0.01). Thirteen CB recipients developed CMV disease, in which five of them had more than one organ involvement. Two patients, who were CB recipients, died of CMV pneumonia. CONCLUSION: This study suggests that CB recipients had both longer and higher cumulative incidences of CMV infection. Therefore, a more aggressive and effective strategy of CMV management should be considered in CB recipients. PMID- 22318830 TI - Herpes simplex virus 2 infection rate and necessity of screening during pregnancy: a clinical and seroepidemiologic study. AB - PURPOSE: This study determined the seroprevalence of herpes virus 2 in gravidas and the differences between herpes virus 2-infected and healthy gravidas. The need to screen gravidas for herpes virus 2 was also evaluated. MATERIALS AND METHODS: A retrospective analysis involving 500 gravidas who underwent herpes virus 2 serologic testing and delivery in our hospital between January 2009 and August 2010 was performed. All patients in the study group were classified as herpes simplex virus 2 (HSV2) positive, and all cases were analyzed with respect to the clinical course of the pregnancy, pregnancy outcome, obstetric complications, and neonatal outcomes. SPSS software (version 14.0) was used for statistical analysis. A chi-square test and Student's t-test were used for statistical analysis. RESULTS: In the current study, the herpes virus 2 seroprevalence rate in gravidas was 17%. There was no significant difference in the rates of preterm delivery, premature rupture of membranes, preterm labor, and intrauterine growth restriction between the herpes virus 2-infected gravidas and the healthy control group. The rates of spontaneous abortion and sexually transmitted disease were higher in the herpes virus 2 infection group than the healthy control group. CONCLUSION: After educating gravidas on genital herpes and, if gravidas thereafter consent to herpes virus 2 screening, the risk of neonatal herpes virus 2 infections can be reduced. In addition, examination of gravidas for sexually transmitted diseases would increase as would appropriate treatment. PMID- 22318831 TI - Treatment of femoral shaft fracture with an interlocking humeral nail in older children and adolescents. AB - PURPOSE: Rigid interlocking nailing for femoral shaft fracture is ideal for use in adolescents in terms of stability of the fracture and convenience for the patient. However, numerous authors have reported that rigid interlocking nailing has some limitations in this age group due to the risk of complications. We evaluated the results of intramedullary nailing for femoral shaft fractures with an interlocking humeral nail in older children and adolescents. MATERIALS AND METHODS: We retrospectively reviewed records of patients treated with an interlocking humeral nail. Radiographs were examined for proximal femoral change and evidence of osteonecrosis. Outcomes were assessed by major or minor complications that occurred after operative treatment. RESULTS: Twenty-four femoral shaft fractures in 23 patients were enrolled. The mean age at the time of operation was 12 years and 8 months and the mean follow- up period was 21 months. Bony union was achieved in all patients without any complications related to the procedure such as infection, nonunion, malalignment and limb length discrepancy. All fractures were clinically and radiographically united within an average eight weeks. No patients developed avascular necrosis of the femoral head and coxa valga. CONCLUSION: Intramedullary nailing through the greater trochanter using a rigid interlocking humeral nail is effective and safe for the treatment of femoral shaft fractures in older children and adolescents. PMID- 22318832 TI - Clinical incidence of sacroiliac joint arthritis and pain after sacropelvic fixation for spinal deformity. AB - PURPOSE: Sacroiliac fixation using iliac screws for highly unstable lumbar spine has been reported with an improved fusion rate and clinical results. On the other hand, there is a potential for clinical problems related to iliac fixation, including late sacroiliac joint arthritis and pain. MATERIALS AND METHODS: Twenty patients were evaluated. Degenerative scoliosis was diagnosed in 7 patients, failed back syndrome in 6 patients, destructive spondyloarthropathy in 4 patients, and Charcot spine in 3 patients. All patients underwent posterolateral fusion surgery incorporating lumbar, S1 and iliac screws. We evaluated the pain scores, bone union, and degeneration of sacroiliac joints by X-ray imaging and computed tomography before and 3 years after surgery. For evaluation of low back and buttock pain from sacroiliac joints 3 years after surgery, lidocaine was administered in order to examine pain relief thereafter. RESULTS: Pain scores significantly improved after surgery. All patients showed bone union at final follow-up. Degeneration of sacroiliac joints was not seen in the 20 patients 3 years after surgery. Patients showed slight low back and buttock pain 3 years after surgery. However, not all patients showed relief of the low back and buttock pain after injection of lidocaine into the sacroiliac joint, indicating that their pain did not originate from sacroiliac joints. CONCLUSION: The fusion rate and clinical results were excellent. Also, degeneration and pain from sacroiliac joints were not seen within 3 years after surgery. We recommend sacroiliac fixation using iliac screws for highly unstable lumbar spine. PMID- 22318833 TI - Anterior pelvic plating and sacroiliac joint fixation in unstable pelvic ring injuries. AB - PURPOSE: To analyze the effectiveness of anterior pelvic plating and subsequent percutaneous sacroiliac joint screw fixation in patients with unstable pelvic ring injuries. MATERIALS AND METHODS: Thirty-two patients were included with twenty-one males and eleven females. The mean age was 41 years (range, 19-76). The mean follow-up period was 51 months (range, 36-73). According to AO-OTA classification, there were 11 cases of B2 injuries, 8 cases of B3 injuries, 9 cases of C1 injuries, 2 cases of C2 injuries and 2 cases of C3 injuries. In the posterior lesions, there were 20 cases of sacral fractures and 12 cases of sacroiliac joint disruptions or dislocations. Anterior pelvic plating and subsequent percutaneous sacroiliac joint fixation were performed. RESULTS: The clinical results were 16 cases of excellent, 10 cases of good, 4 cases of moderate and 2 cases of poor functional results. The 2 cases out of 7 moderate reductions had poor functional results with residual neurologic symptoms. The radiological results were 16 cases of anatomic, 9 cases of nearly anatomic and 7 cases of moderate reduction. All patients were healed except 3 cases of nonunion at the pubic ramus. The complications encountered were 3 cases of screw loosening, 2 cases of anterior plate breakage and 1 case of postoperative infection. CONCLUSION: In patients with unstable pelvic ring injuries, anterior pelvic plating and subsequent percutaneous sacroiliac joint screw fixation may be a useful surgical option. The radiological results and residual neurologic symptoms had effects on its functional results. PMID- 22318834 TI - Beneficial effects of adding ketamine to intravenous patient-controlled analgesia with fentanyl after the Nuss procedure in pediatric patients. AB - PURPOSE: The aim of this prospective, double-blind, randomized study was to investigate the analgesic effects of low-dose ketamine on intravenous patient controlled analgesia (IV-PCA) with fentanyl for pain control in pediatric patients following the Nuss procedure for pectus excavatum. MATERIALS AND METHODS: Sixty pediatric patients undergoing the Nuss procedure were randomly assigned to receive fentanyl (Group F, n=30) or fentanyl plus ketamine (Group FK, n=30). Ten minutes before the end of surgery, following the loading dose of each solution, 0.5 MUg/kg/hr of fentanyl or 0.5 MUg/kg/hr of fentanyl plus 0.15 mg/kg/hr of ketamine was infused via an IV-PCA pump (basal rate, 1 mL/hr; bolus, 0.5 mL; lock out interval, 30 min). Fentanyl consumption, pain score, ketorolac use, nausea/vomiting, ondansetron use, pruritus, respiratory depression, hallucination, dreaming, and parent satisfaction with pain control were measured throughout the 48 hours following surgery. RESULTS: The pain scores, ketorolac use, and fentanyl consumption of Group FK were significantly lower than in Group F (p<0.05). The incidence of nausea/vomiting and ondansetron use in Group FK was significantly lower than in Group F (p<0.05). There were no reports of respiratory depression, hallucination or dreaming. Parent satisfaction with pain control was similar between the two groups. CONCLUSION: We concluded that low dose ketamine added to IV-PCA with fentanyl after the Nuss procedure in pediatric patients can reduce pain scores, consumption of fentanyl, and incidence of nausea/vomiting without increasing side effects. PMID- 22318835 TI - South Korean military service promotes smoking: a quasi-experimental design. AB - PURPOSE: The South Korean (SK) government monopolizes the tobacco industry and is accused of pushing smoking on captive military personnel. However, estimating the association between military service and smoking is difficult, since military service is required for all SK men and the few civilian waivers are usually based on smoking determinants, e.g., social status. MATERIALS AND METHODS: Using a quasi-experimental design we validly estimate the association between military service and smoking. Military service was assigned by immigration patterns to the United States, instead of an experimenter, by comparing Korean Americans who happened to immigrate before or after the age(s) of mandated service. Smoking promotion in the military was also described among SK veterans, to identify the probable mechanisms for veterans' smoking tendencies. RESULTS: Veterans were 15% [95% confidence interval (CI), 4 to 27] more likely to ever-puff and 10% (95% CI, 0 to 23) more likely to ever-smoke cigarettes, compared to a similar group of civilians. Among veterans, 92% (95% CI, 89 to 95) recalled cigarettes were free, 30% (95% CI, 25 to 35) recalled smokers were given more work breaks and 38% (95% CI, 32 to 43) felt explicit "social pressure" to smoke. Free cigarettes was the strongest mechanism for veterans' smoking tendencies, e.g., veterans recalling free cigarette distribution were 16% (95% CI, 1 to 37) more likely to ever-smoke than veterans not recalling. CONCLUSION: These patterns suggest military service is strongly associated with smoking, and differences between veterans and civilians smoking may carry over long after military service. Given military service remains entirely in government purview, actively changing military smoking policies may prove most efficacious. This highlights the importance of recent bans on military cigarette distribution, but policies eliminating other smoking encouragements described by veterans are necessary and could effectively reduce the smoking prevalence by as much as 10% in SK. PMID- 22318836 TI - Antimicrobial susceptibility of Stenotrophomonas maltophilia isolates from a Korean tertiary care hospital. AB - We determined the antimicrobial susceptibility of 90 clinical isolates of Stenotrophomonas maltophilia collected in 2009 at a tertiary care hospital in Korea. Trimethoprim-sulfamethoxazole, minocycline, and levofloxacin were active against most of the isolates tested. Moxifloxacin and tigecycline were also active and hold promise as therapeutic options for S. maltophilia infections. PMID- 22318837 TI - Transumbilical single port laparoscopic adrenalectomy: a technical report on right and left adrenalectomy using the glove port. AB - Recently, single port laparoscopic surgery has been the focus of attention due to the advanced laparoscopic skills accumulated from experience and developments in laparoscopic instruments. Herein, we present two cases of initial single port laparoscopic adrenalectomies. Case 1 was a 38-year-old female patient diagnosed with primary hyperaldosteronism because of a the right adrenal 2.5-cm sized adenoma, and case 2 was a 31-year-old female patient diagnosed with primary adrenal Cushing's syndrome because of a left adrenal 2.9-cm sized adenoma. Both patients successfully underwent single port laparoscopic adrenalectomies via a transumbilical transperitoneal approach. There was no estimated blood loss and the total operating times were 60 and 70 minutes, respectively. Both patients recovered uneventfully. We believe that this technique presented could provide potential benefits (lesser wound pain, better cosmetic satisfaction, and shorter convalescence) if the indications are carefully selected. PMID- 22318838 TI - A case of acute polyneuropathy with nephrotic syndrome showing transient proximal sensory conduction defects. AB - Acute sensorimotor polyneuropathy that resembles Guillain-Barre syndrome (GBS) is rarely accompanied with nephrotic syndrome, and its underlying immunological mechanisms are unclear. A 56-year-old man presented with simultaneous acute progressive symmetric sensorimotor polyneuropathy and proteinuria. A kidney biopsy revealed focal segmental glomerulosclerosis. Serial electrophysiologic studies showed only a transient proximal conduction block in the median nerve, stimulated somatosensory evoked potential and prolonged terminal latencies of the median and peroneal nerves. The patient's neurologic deficits and kidney dysfunction recovered with corticosteroid treatment. Our case showed that somatosensory evoked potential study can be an important objective tool in the diagnosis of acute polyneuropathy with normal distal nerve conduction and that corticosteroids should be considered in the initial treatment of GBS-resembling polyneuropathy associated with nephrotic syndrome. PMID- 22318839 TI - Identification of vulnerable plaque in a stented coronary segment 17 years after implantation using optical coherence tomography. AB - A patient presented with exertional chest pain two months prior to admission. Coronary angiography revealed a subocclusive stenosis within the boundaries of the stent. Optical coherence tomography showed remarkable intimal growth inside the stent, which demonstrated a heterogeneous appearance including low-intensity areas. These findings were congruent with the morphology of fibroatheroma in the native coronary artery and suggested that new atherosclerotic progression of the intima within the stent had occurred over 17 years following bare metal stent implantation. To the best of our knowledge, this is one of the most delayed instances of a bare metal stent restenosis described in the medical literature. PMID- 22318840 TI - The first case of familial Mediterranean fever associated with renal amyloidosis in Korea. AB - Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterized by periodic episodes of fever and recurrent polyserositis. It is caused by a dysfunction of pyrin (or marenostrin) as a result of a mutation within the MEFV gene. It occurs mostly in individuals of Mediterranean origin; however, it has also been reported in non-Mediterranean populations. In this report, we describe the first case of FMF in a Korean child. As eight-year-old boy presented recurrent febrile attacks from an unknown cause, an acute scrotum and renal amyloidosis. He also showed splenomegaly, lymphadenopathy, pleural effusion, ascites and elevated acute phase reactants. After MEFV gene analysis, he was diagnosed as FMF combined with amyloidosis. PMID- 22318841 TI - Self-assembly of borane end-functionalized polystyrene through tris(1 pyrazolyl)borate (Tp) iron(II) linkages. AB - Treatment of trimethylsilane-terminated polystyrenes with BBr(3) resulted in the formation of dibromoboryl-functionalized mono- or ditelechelic styrene polymers. Subsequently, the borane moieties were selectively converted to tris(1 pyrazolyl)borate (Tp) moieties capable of transition metal coordination. These novel telechelic polymers assemble into redox-active supramolecular polymer structures upon reaction with Fe(II) as indicated by GPC, UV-vis, and cyclic voltammetry studies. PMID- 22318842 TI - [Influence of vascular comorbidities on the antioxidant defense system in Alzheimer's disease]. AB - BACKGROUND AND AIM: Oxidative stress is a critical factor in the pathophysiology of dementia, but the role of oxidant/antioxidant imbalance in relation to vascular pathology in the onset and progression of Alzheimer's disease (AD) is poorly understood. The aim of this study was the identification of an association between vascular comorbidities/vascular risk factors and plasma levels of antioxidant micronutrients in patients with AD. PATIENTS AND METHODS: 41 patients with AD and 34 controls were included in the study. Atherosclerosis (increased intima-media thickness of the common carotid artery) and/or type 2 diabetes mellitus were diagnosed in 21 AD patients (AD Plus group). 20 patients with AD were free of vascular comorbidities and risk factors (AD group). A neuropsychological assessment (Mini-Mental State Examination, MMSE; Clock drawing test; DemTect) and the measurement of plasma levels of lipophilic micronutrients including retinol (vitamin A), alpha-tocopherol (vitamin E), lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene and beta-carotene by HPLC were performed in all study subjects. RESULTS: Plasma levels of retinol, vitamin E, lutein, zeaxanthin, lycopene and beta-carotene were significantly lower in the AD Plus group than in controls. Furthermore, vitamin A levels were correlated with MMSE scores and the levels of vitamin E, lutein, zeaxanthin and lycopene were correlated with all neuropsychological tests. CONCLUSION: The depletion of circulating antioxidant micronutrients observed in AD patients is associated with vascular comorbidities and risk factors. The vascular comorbidities of patients with AD should also be identified in light of the presence and degree of depletion of the antioxidant defense system of the organism. This might lead to a better lifestyle-related counselling of patients with AD and their caregivers, with possible positive preventive effects on worsening in the long run. Further studies with a larger patient sample are needed to verify the negative effect of vascular pathology in AD-related oxidative stress. PMID- 22318843 TI - [From mice to men - insights from the hantavirus epidemic in 2010]. AB - HISTORY AND ADMISSION FINDINGS: With 2017 notified cases the largest hantavirus epidemic in Germany has occurred in 2010. We report on two interesting cases illustrating the wide range of the individual clinical course and the diagnostic problems in hantavirus disease. The first patient was a seriously ill 44-year-old man who needed dialysis after an onset of flu-like symptoms with oliguria. An initially negative result of a hantavirus serology focused attention on rapidly progressive glomerulonephritis. The second patient, a 22-year-old man, presented with severe neurological symptoms with seizures. TREATMENT AND COURSE: Pathological examination of the renal-biopsy specimen in Case 1 reportedly showed the typical pattern of tubulointerstitial damage in the renal cortex and the outer medulla as in hantavirus infection. In a repeated analysis Puumala virus RNA as a marker of acute infection was found. After dialysis and administration of higher-dose systemic glucocorticoids the patient slowly recovered. In Case 2 the severe neurological symptoms caused a complete neurological diagnostic with lumbar puncture and MRI before the detection of specific antibodies and Puumala virus RNA showed that nephropathia epidemica was the disease. The patient recovered after 10 days. CONCLUSION: Because of the variability of symptoms and the extrarenal manifestations of the disease the nephropathia epidemica can occasionally cause problems of differential diagnosis. A rapid diagnosis is important because of the urgent differentiation of other renal diseases with bad prognosis. PMID- 22318844 TI - [Progredient dyspnea and poor drainage in a peritoneal dialysis patient - case 2/2012]. AB - HISTORY AND ADMISSION FINDINGS: We report on a peritoneal dialysis patients who presented with dyspnea, poor drainage and weight gain. INVESTIGATIONS: A chest x ray showed a large pleural effusion on the right side. Thoracocentesis revealed a clear protein-devoid fluid with a glucose concentration greater than that of plasma. By intraperitoneal administration of toluidine blue, a pleuroperitoneal leakage was proven. DIAGNOSIS, TREATMENT AND COURSE: The patient underwent video assisted thoracoscopy revealing a total of four spots of pleuroperitoneal leakage on the diaphragm after intraperitoneal administration of toluidine blue. Closure was attempted with the aid of a prolene patch which was stiched onto the diaphragm inducing adhesion to the lung. After three months bridging with hemodialysis, the peritoneal dialysis was commenced again without a recurrence of the leakage. CONCLUSIONS: Pleuroperitoneal leakage can occur during the course of peritoneal dialysis treatment leading to hydrothorax. Video-assisted thoracoscopy and patching of the diaphragm with a prolene mesh can be used to treat these patients. PMID- 22318845 TI - [71-year-old patient on dialysis with necrosis of the skin]. PMID- 22318846 TI - [Chronobiology of blood pressure and chronopharmacotherapy of arterial hypertension]. AB - Arterial blood pressure is subject to a circadian rhythm that results in a fall of blood pressure during the night. In patients with diabetes, renal insufficiency, left-ventricular hypertrophy, sleep apnea, hypertension of pregnancy, and different forms of secondary hypertension a nocturnal fall of blood pressure is even abandoned or reverted. Diagnosis is made using 24-h blood pressure measurement, which is however used not frequently enough for a clinical assessment or adjustment of therapy. An adaption of the selection or the time of administration of antihypertensive drugs with respect to the circadian rhythm is beneficial to control blood pressure and reduce cardiovascular morbidity. This is particularly true for patients with an a non- or inverted dipping blood pressure pattern, in which the bedtime dosing may result in a normalization of blood pressure and restoration of a normal circadian rhythm. The present manuscript reviews the chronopharmacotherapy of arterial hypertension and grant practical recommendations for their translation into clinical practice. PMID- 22318847 TI - [The role of stem cells in acute kidney injury: myths and potential]. PMID- 22318848 TI - [Secondary osteoporosis - relevant clinical characteristics in diagnosis and therapy]. AB - Osteoporosis is a systemic skeletal disease causing increased fracture risk. According to pathogenesis, primary (70 - 80 %) and secondary osteoporosis (20 - 30 %) are distinguished. Secondary osteoporosis comprises all entities in which osteoporosis is predominantly and causally associated with certain diseases or conditions. The aim of this review article is to put attention to special features in diagnosis, prophylaxis and treatment of secondary osteoporosis in general and to demonstrate some forms of secondary osteoporosis which seem particularly important during clinical practice. The manuscript refers to the guidelines of the DVO 2009 for prevention, diagnosis and therapy of osteoporosis and selective original papers considering the special types of secondary osteoporosis. History, clinical examination and basic laboratory tests are indicative for the diagnosis of secondary osteoporosis. Its clinical presentation is frequently characterized by rapid development and multiple fractures. Therefore, early diagnosis, prophylaxis and causal treatment is decisive. If causal treatment is impossible, risk adaption of bone mineral density (BMD) for osteoporosis specific treatment is essential. Common causes are medications, endocrine, gastrointestinal and hematologic diseases. Glucocorticoid induced osteoporosis, antihormonal therapy (aromatase inhibitor in women with breast cancer, androgen deprivation therapy in men with prostate cancer) and vitamin D deficiency causing secondary hyperparathyroidism are presented in detail. History and basic laboratory testing are decisive to identify possible causes for secondary osteoporosis and to initiate early diagnostic procedures. The risk of severe osteoporosis can be reduced by early and causal treatment or by risk stratified early bone specific medication if causal therapy is impossible. PMID- 22318849 TI - [Platinum-based chemotherapy in triple negative breast cancer]. AB - Since its first market authorisation 40 years ago, cisplatin is an important constituent of cytostatic chemotherapy regimens. Some tumour entities even lost their fright after introduction of cisplatin into the therapeutic armamentarium. For instance, cure rates of up to 95 % are reported for testicular cancer depending on the tumour-stage at the time of diagnosis. In the first-line breast cancer therapy cisplatin is regarded only a cytostatic reserve at present. However, platinum-based therapy regimes are widely used in anthracyclin- and/or taxan-refractory situations. In addition, platinum-based therapy is well established in the palliative treatment of breast cancer.Breast cancer is the most common female cancer type and triple negative breast cancer (TNBC) has the poorest prognosis. Therapy options are limited to surgery, radiotherapy, and polychemotherapy since targeted therapies, which are based on a molecular interaction with a target protein, are not amenable at present. However, triple negative breast cancer specimens show good initial response to platinum-based chemotherapy. Therefore, clinical research of cisplatin therapy in BRCA-mutated triple negative breast cancer is currently intensified. However, despite successful first treatment, the tumour often reappears quickly, a phenomenon designated as the triple negative paradox. Throughout this article, current indications and possible future development to a potentially new indication is outlined. PMID- 22318850 TI - Seroprevalence of feline immunodeficiency virus, feline leukaemia virus and Toxoplasma gondii in stray cat colonies in northern Italy and correlation with clinical and laboratory data. AB - Stray cat colonies in urban and rural areas of Lombardy, northern Italy, were surveyed for seroprevalence of feline immunodeficiency virus (FIV) antibodies, feline leukaemia virus (FeLV) antigen and Toxoplasma gondii IgG. Of 316 cats tested, 6.6% were positive for FIV and 3.8% were positive for FeLV infection; 203 cats were tested for T gondii IgG antibodies and a prevalence of 30.5% was detected. Statistical analysis tested the influence of provenience, age, gender, health status and laboratory results on seroprevalence and found male gender and adult age were risk factors for FIV infection. FIV-infected cats were more likely to have a decreased red blood cell count than FIV seronegative cats. No predictors were significantly associated with FeLV and T gondii seropositivity. Colony cats in this study posed a limited risk for retrovirus infection to pet cats allowed outdoors, whereas toxoplasmosis exposure was comparable with the worldwide data. PMID- 22318851 TI - Muscle mass scaling in primates: an energetic and ecological perspective. AB - Body composition is known to vary dramatically among mammals, even in closely related species, yet this issue has never been systematically investigated. Here, we examine differences in muscle mass scaling among mammals, and explore how primate body composition compares to that of nonprimate mammals. We use a literature-based sample of eutherian and metatherian mammals, and combine this with new dissection-based data on muscularity in a variety of strepsirrhine primates and the haplorhine, Tarsius syrichta. Our results indicate an isometric scaling relationship between total muscle mass and total body mass across mammals. However, we documented substantial variation in muscularity in mammals (21-61% of total body mass), which can be seen both within and between taxonomic groups. We also found that primates are under-muscled when compared to other mammals. This difference in body composition may in part reflect the functional consequences of arboreality, as arboreal species have significantly lower levels of muscularity than terrestrial species. PMID- 22318852 TI - Sudden cardiac death and malignant arrhythmias: the scope of the problem in adult congenital heart patients. AB - A key component of recognizing sudden cardiac death (SCD) risk in the adult congenital heart disease (ACHD) patient is the recognition of heart failure risk for each physiology. The risk of SCD is an accrued phenomenon, representing the influences of anatomy, genetics, surgical and catheter interventions, and long term sequelae of residual hemodynamic issues. These all lead to a substrate for tachyarrhythmia. It is beneficial in thinking about all of the potential combinations of CHD anatomy and physiologies to categorize SCD risk for the ACHD patient in terms of systemic left-ventricular failure, systemic right-ventricular failure, subpulmonary ventricular failure, the dyssynchronous contractility states due to bundle branch block, and single-site ventricular pacing. This article reviews important issues in arrhythmogenesis for ACHD patients with all of these physiologies and discusses potential cardiac rhythm device-management needs. PMID- 22318853 TI - Identifying arrhythmias in adults with congenital heart disease by 24-h ambulatory electrocardiography. AB - Adults with congenital heart disease (CHD) are at risk for the development of arrhythmias. This study aimed to assess the incidence of unsuspected arrhythmias among adults with CHD identified on electrocardiograms (ECGs) and 24-h ambulatory electrocardiographic monitoring (Holter monitoring). A review of the cardiology database at the authors' institution from July 2004 through December 2007 identified all clinic patients 18 years old or older who had a recent ECG and Holter monitoring. Data collection included diagnosis, ECG and Holter monitoring results, arrhythmias, and the presence or absence of symptoms. The review identified 140 patients. Analysis of the ECGs showed that 15% of the patients had an arrhythmia. These arrhythmias consisted of ectopy (6%), supraventricular tachycardia (SVT) (3%), pacemaker issues (2%), and previously unrecognized atrioventricular block (AVB) (1%). The majority of the patients with arrhythmias were asymptomatic (76%). Analysis of the Holter monitoring results showed that 31% of the patients had arrhythmias consisting of ectopy (17%), SVT (12%), ventricular tachycardia (7%), high-grade AVB (5%), and pacemaker issues (3%). Of the patients with arrhythmias, 80% were asymptomatic. Among the patients without arrhythmias on ECG, 26% had arrhythmias noted on Holter monitoring. Of the patients with multiple Holter monitorings performed, 34% had a new arrhythmia noted on repeat monitoring. In conclusion, arrhythmias were present in a significant number of adults with CHD, but the majority were asymptomatic. Among adults with CHD, even those with normal ECGs, arrhythmias were frequently detected on Holter monitoring. In addition, repeat Holter monitoring may identify significant arrhythmias over time. PMID- 22318854 TI - Optineurin immunoreactivity in neuronal nuclear inclusions of polyglutamine diseases (Huntington's, DRPLA, SCA2, SCA3) and intranuclear inclusion body disease. PMID- 22318855 TI - Intercage electron transfer driven by electric field in Robin-Day-type molecules. AB - A new class of isomers, namely, intercage electron-transfer isomers, is reported for fluorinated double-cage molecular anion e(-)@C(20)F(18)(NH)(2)C(20)F(18) with C(20)F(18) cages: 1 with the excess electron inside the left cage, 2 with the excess electron inside both cages, and 3 with the excess electron inside the right cage. Interestingly, the C(20)F(18) cages may be considered as two redox sites existing in a rare nonmetal mixed-valent (0 and -1) molecular anion. The three isomers with two redox sites may be the founding members of a new class of mixed-valent compounds, namely, nonmetal Robin-Day Class II with localized redox centers for 1 and 3, and Class III with delocalized redox centers for 2. Two intercage electron-transfers pathways involving transfer of one or half an excess electron from one cage to the other are found: 1) Manipulating the external electric field (-0.001 a.u. for 1->3 and -0.0005 a.u. for 1->2) and 2) Exciting the transition from ground to first excited state and subsequent radiationless transition from the excited state to another ground state for 1 and 3. For the exhibited microscopic electron-transfer process 1->3, 2 may be the transition state, and the electron-transfer barrier of 6.021 kcal mol(-1) is close to the electric field work of 8.04 kcal mol(-1). PMID- 22318856 TI - Influence of acid hydrolysis on thermal and rheological properties of amaranth starches varying in amylose content. AB - BACKGROUND: The granules of amaranth starch are very small compared with starches from other sources. In the current work, amaranth starches with different amylose contents were treated with hydrochloric acid as a function of time in order to study the effect of acid treatments on starches. Differential scanning calorimetry and dynamic oscillation in shear were employed to analyse the thermal and rheological properties of acid-modified amaranth starch. RESULTS: Results showed that gelatinisation temperatures and enthalpy change of gelatinisation (DeltaH) decreased steeply initially, and had a slight increase with further treatment up to 12 h then decreased, an outcome that reflected distinct resistance to acid with various amylose contents. Rheological parameters of storage and loss moduli during heating, cooling and frequency sweep of modified starches reflected the differential scanning calorimetry results by decreasing in value as the time of acid hydrolysis increased. CONCLUSION: With amylose content increase, the effects of acid hydrolysis on gelatinisation temperatures became less pronounced. Nevertheless, prolonged acid hydrolysis decreased the storage and loss moduli, with the starch pastes becoming more liquid-like. PMID- 22318857 TI - Anisotropic wetting surfaces with one-dimensional and directional structures: fabrication approaches, wetting properties and potential applications. AB - This review article provides a brief summary of recent research progress on anisotropic wetting on one-dimensional (1D) and directionally patterned surfaces, as well as the technical importance in various applications. Inspiration from natural structures exhibiting anisotropic wetting behavior is first discussed. Development of fabrication techniques for topographically and chemically 1D patterned surfaces and directional nanomaterials are then reviewed, with emphasis on anisotropic behavior with topographically (structurally) patterned surfaces. The basic investigation of anisotropic wetting behavior and theoretical simulations for anisotropic wetting are also further reviewed. Perspectives concerning future direction of anisotropic wetting research and its potential applications in microfluidic devices, lab-on-a-chip, sensor, microreactor and self-cleaning are presented. PMID- 22318858 TI - Quantum molecular mechanics-a noniterative procedure for the fast ab Initio calculation of closed shell systems. AB - In this article, we advance the foundations of a strategy to develop a molecular mechanics method based not on classical mechanics and force fields but entirely on quantum mechanics and localized electron-pair orbitals, which we call quantum molecular mechanics (QMM). Accordingly, we introduce a new manner of calculating Hartree-Fock ab initio wavefunctions of closed shell systems based on variationally preoptimized nonorthogonal electron pair orbitals constructed by linear combinations of basis functions centered on the atoms. QMM is noniterative and requires only one extremely fast inversion of a single sparse matrix to arrive to the one-particle density matrix, to the electron density, and consequently, to the ab initio electrostatic potential around the molecular system, or cluster of molecules. Although QMM neglects the smaller polarization effects due to intermolecular interactions, it fully takes into consideration polarization effects due to the much stronger intramolecular geometry distortions. For the case of methane, we show that QMM was able to reproduce satisfactorily the energetics and polarization effects of all distortions of the molecule along the nine normal modes of vibration, well beyond the harmonic region. We present the first practical applications of the QMM method by examining, in detail, the cases of clusters of helium atoms, hydrogen molecules, methane molecules, as well as one molecule of HeH(+) surrounded by several methane molecules. We finally advance and discuss the potentialities of an exact formula to compute the QMM total energy, in which only two center integrals are involved, provided that the fully optimized electron-pair orbitals are known. PMID- 22318859 TI - Microwave-assisted extraction combined with dispersive liquid-liquid microextraction as a new approach to determination of chlorophenols in soil and sediments. AB - A new method was applied for extraction of five chlorophenols from soil and marine sediment samples. Microwave-assisted extraction coupled with dispersive liquid-liquid microextraction followed by semi-automated in-syringe back extraction technique was used as an extraction technique. Microwave-assisted extraction was performed by using 2.0 mL of alkaline water at pH 10.0. After extraction, the pH of extraction solution was adjusted at 6.0 and dispersive liquid-liquid microextraction procedure was done using 1.0 mL of acetone as a disperser solvent and 37.0 MUL of chlorobenzene as extraction solvent. About 20.0 +/- 0.5 MUL sedimented phase was collected after centrifugation step. Then, chlorophenols were back extracted into 20 MUL of alkaline water at pH 12.0 within the microsyringe. Finally, 20.0 MUL of aqueous solution was injected into high performance liquid chromatography with ultra violet detection for analysis. The obtained recovery and preconcentration factors for the analytes were in the range of 68.0-82.0% and 25-30, respectively, with relative standard deviations <=7.6%. The limits of the detection were found in the range of 0.0005-0.002 mg/kg. The method provides a simple and fast procedure for the extraction and determination of chlorophenols in soil and marine sediment samples. PMID- 22318860 TI - Biological glucose metabolism regulated peptide self-assembly as a simple visual biosensor for glucose detection. AB - A glucose oxidase (GOx)-mediated glucose metabolism was in vitro mimicked and employed to regulate the self-assembly of peptide-based building blocks. In this new stimuli-responsive self-assembly system, two peptide-based building blocks, respectively, having aspartic acid (gelator 1) and lysine (gelator 2) residues were designed and prepared. When adding glucose and GOx to the aqueous solution of gelator 1 or the self-assembled fibrillar hydrogel of gelator 2 to construct glucose metabolism system, the metabolic product (gluconic acid) can trigger the protonation of the peptide molecules and induce the phase transitions of gelators 1 (sol-gel) and 2 (gel-sol). Because this glucose metabolism regulated peptide self-assembly is built on the oxidation of glucose, it can be used as a simple visual biosensor for glucose detection. PMID- 22318862 TI - Arabidopsis type-III phosphatidylinositol 4-kinases beta1 and beta2 are upstream of the phospholipase C pathway triggered by cold exposure. AB - Phosphatidylinositol-4-phosphate (PtdIns4P) is the most abundant phosphoinositide in plants and the precursor of phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P(2)]. This lipid is the substrate of phosphoinositide-dependent phospholipase C (PI-PLC) that produces diacylglycerol (DAG) which can be phosphorylated to phosphatidic acid (PtdOH). In plants, it has been suggested that PtdIns4P may also be a direct substrate of PI-PLC. Whether PtdIns4P is the precursor of PtdIns(4,5)P(2) or a substrate of PI-PLC, its production by phosphatidylinositol-4-kinases (PI4Ks) is the first step in generating the phosphoinositides hydrolyzed by PI-PLC. PI4Ks can be divided into type-II and type-III. In plants, the identity of the PI4K upstream of PI-PLC is unknown. In Arabidopsis, cold triggers PI-PLC activation, resulting in PtdOH production which is paralleled by decreases in PtdIns4P and PtdIns(4,5)P(2). In suspension cells, both the PtdIns4P decrease and the PtdOH increase in response to cold were impaired by 30 MUM wortmannin, a type-III PI4K inhibitor. Type-III PI4Ks include AtPI4KIIIalpha1, beta1 and beta2 isoforms. In this work we show that PtdOH resulting from the PI-PLC pathway is significantly lowered in a pi4kIIIbeta1beta2 double mutant exposed to cold stress. Such a decrease was not detected in single pi4kIIIbeta1 and pi4kIIIbeta2 mutants, indicating that AtPI4KIIIbeta1 and AtPI4KIIIbeta2 can both act upstream of the PI-PLC. Although several short-term to long-term responses to cold were unchanged in pi4kIIIbeta1beta2, cold induction of several genes was impaired in the double mutant and its germination was hypersensitive to chilling. We also provide evidence that de novo synthesis of PtdIns4P by PI4Ks occurs in parallel to PI-PLC activation. PMID- 22318863 TI - Nitrate addition alleviates ammonium toxicity without lessening ammonium accumulation, organic acid depletion and inorganic cation depletion in Arabidopsis thaliana shoots. AB - When ammonium is the sole nitrogen (N) source, plant growth is suppressed compared with the situation where nitrate is the N source. This is commonly referred to as ammonium toxicity. It is widely known that a combination of nitrate and ammonium as N source alleviates this ammonium toxicity (nitrate dependent alleviation of ammonium toxicity), but the underlying mechanisms are still not completely understood. In plants, ammonium toxicity is often accompanied by a depletion of organic acids and inorganic cations, and by an accumulation of ammonium. All these factors have been considered as possible causes for ammonium toxicity. Thus, we hypothesized that nitrate could alleviate ammonium toxicity by lessening these symptoms. We analyzed growth, inorganic N and cation content and various primary metabolites in shoots of Arabidopsis thaliana seedlings grown on media containing various concentrations of nitrate and/or ammonium. Nitrate-dependent alleviation of ammonium toxicity was not accompanied by less depletion of organic acids and inorganic cations, and showed no reduction in ammonium accumulation. On the other hand, shoot growth was significantly correlated with the nitrate concentration in the shoots. This suggests that nitrate-dependent alleviation of ammonium toxicity is related to physiological processes that are closely linked to nitrate signaling, uptake and reduction. Based on transcript analyses of various genes related to nitrate signaling, uptake and reduction, possible underlying mechanisms for the nitrate dependent alleviation are discussed. PMID- 22318864 TI - Comparison of plasma membrane proteomic changes of Arabidopsis suspension cultured cells (T87 Line) after cold and ABA treatment in association with freezing tolerance development. AB - The plasma membrane (PM) is the primary site of freezing injury in plants. To determine global changes in PM protein profiles in association with freezing tolerance development, proteome analysis of the purified PM of Arabidopsis suspension-cultured cells (T87 line) was conducted with label-free protein quantification technology. Freezing tolerance of Arabidopsis cells at the lag growth phase (8 d old) increased after cold acclimation (CA) or ABA treatment. Proteome analysis assigned 658 proteins in the PM in total, of which 45.3% (298 proteins) were predicted to have transmembrane domains. They were classified into several functional categories, with the primary categories being proteins in transporters, signal transduction, protein destination and storage, and cell structure. After CA, 271 proteins increased and 111 proteins decreased. ABA treatment resulted in 185 increased and 56 decreased proteins. Of these, 139 increased and 49 decreased proteins were identified in common after both CA and ABA treatment. In addition, there were proteins specifically expressed in cold- (132 increased and 62 decreased) or ABA- (46 increased and 7 decreased) treated cells. Collectively, our results clearly show that (i) responses of the PM proteome to CA and ABA treatment overlap substantially but, at the same time, some proteins exhibited different response patterns in each treatment; and (ii) the majority of ABA-responsive proteins are CA-responsive proteins but not vice versa, suggesting complex interactions of CA and ABA signaling pathways in the PM proteome responses. PMID- 22318865 TI - Differential WNT activity in colorectal cancer confers limited tumorigenic potential and is regulated by MAPK signaling. AB - Colorectal cancers (CRC) express the WNT effector protein beta-catenin in a heterogeneous subcellular pattern rather than uniformly in the nucleus. In this study, we investigated this important aspect of molecular heterogeneity in CRCs by analyzing its basis and relationship with tumor-initiating capability. CRC cells with the highest WNT levels showed only a marginal increase in tumor initiation capacity. Notably, high WNT activity correlated with a coincident activation of robust mitogen-activated protein kinase (MAPK) signaling, which when upregulated by KRAS expression or downregulated by epidermal growth factor receptor inhibition elicited parallel effects on WNT activity. These findings suggested that on its own high WNT activity may not be a reliable signifier of tumor-initiating potential or stem-like potential. Furthermore, they suggest that MAPK signaling is a critical modifier of intratumoral heterogeneity that contributes significantly to determining the impact of WNT activity on stemness phenotypes in colon cancer cells. PMID- 22318866 TI - Intracellular tumor-associated antigens represent effective targets for passive immunotherapy. AB - Monoclonal antibody (mAb) therapy against tumor antigens expressed on the tumor surface is associated with clinical benefit. However, many tumor antigens are intracellular molecules that generally would not be considered suitable targets for mAb therapy. In this study, we provide evidence challenging this view through an investigation of the efficacy of mAb directed against NY-ESO-1, a widely expressed immunogen in human tumors that is expressed intracellularly rather than on the surface of cells. On their own, NY-ESO-1 mAb could neither augment antigen specific CD8(+) T-cell induction nor cause tumor eradication. To facilitate mAb access to intracellular target molecules, we combined anti-NY-ESO-1 mAb with anticancer drugs to accentuate the release of intracellular NY-ESO-1 from dying tumor cells. Strikingly, combination therapy induced a strong antitumor effect that was accompanied by the development of NY-ESO-1-specific effector/memory CD8(+) T cells that were not elicited by single treatments alone. The combinatorial effect was also associated with upregulation of maturation markers on dendritic cells, consistent with the organization of an effective antitumor T cell response. Administration of Fc-depleted F(ab) mAb or combination treatment in Fcgamma receptor-deficient host mice abolished the therapeutic effect. Together, our findings show that intracellular tumor antigens can be captured by mAbs and engaged in an efficient induction of CD8(+) T-cell responses, greatly expanding the possible use of mAb for passive cancer immunotherapy. PMID- 22318867 TI - An evaluation of the efficacy of video displays for use with chimpanzees (Pan troglodytes). AB - Video displays for behavioral research lend themselves particularly well to studies with chimpanzees (Pan troglodytes), as their vision is comparable to humans', yet there has been no formal test of the efficacy of video displays as a form of social information for chimpanzees. To address this, we compared the learning success of chimpanzees shown video footage of a conspecific compared to chimpanzees shown a live conspecific performing the same novel task. Footage of an unfamiliar chimpanzee operating a bidirectional apparatus was presented to 24 chimpanzees (12 males, 12 females), and their responses were compared to those of a further 12 chimpanzees given the same task but with no form of information. Secondly, we also compared the responses of the chimpanzees in the video display condition to responses of eight chimpanzees from a previously published study of ours, in which chimpanzees observed live models. Chimpanzees shown a video display were more successful than those in the control condition and showed comparable success to those that saw a live model. Regarding fine-grained copying (i.e. the direction that the door was pushed), only chimpanzees that observed a live model showed significant matching to the model's methods with their first response. Yet, when all the responses made by the chimpanzees were considered, comparable levels of matching were shown by chimpanzees in both the live and video conditions. PMID- 22318868 TI - Expression and localization of ryanodine receptors in the frog semicircular canal. AB - Several experiments suggest an important role for store-released Ca2+ in hair cell organs: drugs targeting IP3 and ryanodine (RyRs) receptors affect release from hair cells, and stores are thought to be involved in vesicle recycling at ribbon synapses. In this work we investigated the semicircular canal distribution of RyRs by immunofluorescence, using slice preparations of the sensory epithelium (to distinguish cell types) and flat mounts of the simpler nonsensory regions. RyRs were present in hair cells, mostly in supranuclear spots, but not in supporting cells; as regards nonsensory regions, they were also localized in dark cells and cells from the ductus. No labeling was found in nerve terminals, although nerve branches could be observed in proximity to hair cell RyR spots. The differential expression of RyR isoforms was studied by RT-PCR and immunoblotting, showing the presence of RyRalpha in both ampulla and canal arm and RyRbeta in the ampulla only. PMID- 22318869 TI - Materializing Performance and Ritual: Decoding the Archaeology of Movement in Tallensi Shrines in Northern Ghana. AB - Within much archaeological interpretation and conceptualization in relation to ritual and religion the static is often given prominence. This is potentially due to the fact that static material residues are being considered and, in turn, this static image is transferred onto the ritual practices, beliefs, and communities that generated the archaeological material. Instead some of the material encountered archaeologically might be structured by much more dynamic, fluid, and active ritual behaviors. Considering performance, movement, and bodily understandings in relation to space and material culture offers a potential mechanism to begin to explore this, and will be considered with reference to the Golib festival and the archaeology of Tallensi shrines in the Tongo Hills of the Upper East Region in Northern Ghana. PMID- 22318870 TI - Association of serum 25-hydroxyvitamin D with type 2 diabetes and markers of insulin resistance in a general older population in Finland. AB - BACKGROUND: Vitamin D insufficiency and type 2 diabetes are both common in Finland, and low vitamin D status has been suggested as a risk factor for type 2 diabetes. Our aim was to study the associations between serum 25-hydroxyvitamin D [25(OH)D], a marker of vitamin D status, and glucose homeostasis and type 2 diabetes in a general population sample in Eastern Finland. METHODS: Cross sectional analysis in the Kuopio Ischaemic Heart Disease Risk Factor Study. A total of 850 men and 906 women, aged 53-73 years, were analysed. Relative risk (RR) of prevalent diabetes was estimated as odds ratios by logistic regression. Associations between serum 25(OH)D and markers of impaired glucose metabolism in tertiles of serum 25(OH)D concentration were assessed by linear regression. RESULTS: The mean serum 25(OH)D concentration was 43.4 nmol/L (SD 17.6, range 8.5 122.8 nmol/L) in the study population. Serum 25(OH)D concentration <50 nmol/L were observed in 65.5% of the participants. Serum 25(OH)D was inversely associated with fasting serum insulin, fasting blood glucose and oral glucose tolerance test (OGTT) 2-h glucose levels after adjustment for age, gender and examination year. Association with the OGTT 2-h glucose remained statistically significant after multivariate adjustments. The RR (95% confidence interval) for type 2 diabetes in tertiles of serum 25(OH)D were 1, 1.26 (0.86, 1.85) and 1.44 (0.96, 2.15) after multivariate adjustments (p for trend = 0.08). CONCLUSIONS: Our results suggest that low serum 25(OH)D is associated with impaired glucose and insulin metabolism. PMID- 22318871 TI - Non linear optical microscopy of adipose-derived stem cells induced towards osteoblasts and adipocytes. AB - Adipose-derived stem cells (ADSCs) are adult stem cells isolated from lipoaspirates. They are a good candidate for autologuous cell therapy and tissue engineering. For these applications, label-free imaging could be critical to assess noninvasively the efficiency of stem cell (SC) differentiation. We report on the development and application of a multimodal microscope to monitor and quantify ADSC differentiation into osteoblasts and adipocytes. PMID- 22318872 TI - Estimate of deaths due to valvular insufficiency attributable to the use of benfluorex in France. AB - PURPOSE: To estimate the number of deaths from valvular insufficiency caused by the use of the fenfluramine-derivative benfluorex during the period 1976-2009 in France. METHODS: Our calculation was based on (i) the exposure level to benfluorex in the French population, derived from sales figures for the period 1976-2009 and from the main characteristics of benfluorex use provided by the French health products safety agency; (ii) the relative risk of hospitalization for valvular insufficiency among exposed compared with unexposed individuals with diabetes, originating from a cohort study based on a French medico-administrative database, with benfluorex exposure assessed in 2006; (iii) the incidence of hospitalization for valvular insufficiency among exposed individuals, originating from the same database; and (iv) the mortality associated with valvular heart disease. RESULTS: In France, use of benfluorex during the period 1976-2009 is likely to be responsible for around 3100 hospitalizations and 1300 deaths due to valvular insufficiency. These figures may be underestimations. CONCLUSIONS: The grave consequences benfluorex use have had for many people lend support to the public investigation, which has been set to understand the reasons that have contributed to the delay in withdrawing benfluorex from the French market. PMID- 22318873 TI - The influence of iron availability on human salivary microbial community composition. AB - It is a well-recognized fact that the composition of human salivary microbial community is greatly affected by its nutritional environment. However, most studies are currently focused on major carbon or nitrogen sources with limited attention to trace elements like essential mineral ions. In this study, we examined the effect of iron availability on the bacterial profiles of an in vitro human salivary microbial community as iron is an essential trace element for the survival and proliferation of virtually all microorganisms. Analysis via a combination of PCR with denaturing gradient gel electrophoresis demonstrated a drastic change in species composition of an in vitro human salivary microbiota when iron was scavenged from the culture medium by addition of the iron chelator 2,2'-bipyridyl. This shift in community profile was prevented by the presence of excessive ferrous iron (Fe(2+)). Most interestingly, under iron deficiency, the in vitro grown salivary microbial community became dominated by several hemolytic bacterial species, including Streptococcus spp., Gemella spp., and Granulicatella spp. all of which have been implicated in infective endocarditis. These data provide evidence that iron availability can modulate host-associated oral microbial communities, resulting in a microbiota with potential clinical impact. PMID- 22318874 TI - Mesoporous silica-coated gold nanorods as a light-mediated multifunctional theranostic platform for cancer treatment. AB - Mesoporous silica-coated gold nanorods (Au@SiO(2)) are developed as a promising and versatile theranostic platform for cancer treatment. Intracellular localization of Au@SiO(2) is visualized through two-photon imaging. With doxorubicin hydrochloride loaded, Au@SiO(2)-DOX show two light-mediated therapeutic modes: low power density laser-triggered drug release for chemotherapy, and high power density laser-induced hyperthermia, which suggest the potential for in-vivo applications. PMID- 22318875 TI - Solubilization of a pi-conjugating hydrophobic dendrimer in aqueous media. AB - Phenylazomethine dendrimers, which can be used as the template for precise metal nanoparticles, are soluble only in aprotic media. The use of a specific surfactant enabled their solubilization in aqueous solutions. Under dilute condition, they formed discrete micelles with a size close to the that of the dendrimer. Condensation resulted in their aggregation; however, they remained in a homogeneous solution without precipitation. Furthermore, each micelle was well isolated. The triplet-excited state of the zinc porphyrin core in the micelles was significantly stable, suggesting the formation of rigid core-shell micelles preventing any external molecules from approaching to the core. PMID- 22318876 TI - (sigma3,lambda5)-Phosphoranes versus (sigma3,lambda3)-thiaphosphiranes: quantum chemical investigation of products of phosphaalkene sulfurization. AB - By sulfurization of phosphaalkenes (a) either (sigma(3),lambda(5))-phosphoranes (b) or (sigma(3),lambda(3))-thiaphosphiranes (c) are formed. In this study, Density Functional Theory (DFT) and coupled cluster (CCSD(T)) calculations have been carried out for model and experimental structures of (sigma(3),lambda(5)) phosphoranes and (sigma(3),lambda(3))-thiaphosphiranes to elucidate the factors influencing relative stabilities of b and c. According to the results of quantum chemical calculations, sterically bulky substituents make the phosphorane form more favored. Conversely, electronic effects of the most substituents provide higher stability for thiaphosphirane isomers. The only exception has been found in the cases where the substituent at the phosphorus atom possesses pi-donor and sigma-acceptor properties (e.g., in the case of amino group) and the substituents at carbon atom exhibit sigma-donor/pi-acceptor effects (e.g., silyl groups). The stability of the cyclic form c decreases further, if the substituents at the carbon atom are amino groups. In this case, a quite unusual structure has been theoretically predicted, which is considerably different from those of the hitherto known phosphoranes. It indicates a pyramidal configuration at the phosphorus atom and can be conventionally presented as a donor-acceptor adduct of diaminocarbene with thioxophosphine. PMID- 22318877 TI - In vivo relevance of citrullinated proteins and the challenges in their detection. AB - Citrullination is a posttranslational modification of arginine. It plays both a physiological role, for instance during apoptosis and epigenetics, and a pathological role in cancer or diseases of the central nervous system. Most research on citrullination to date focuses on its role in auto-immune diseases such as multiple sclerosis and rheumatoid arthritis. In this context, the exact knowledge of citrullination sites in a protein can provide invaluable information about the etiological importance of these citrullinated proteins. However, few techniques exist that can accurately detect citrullination on the peptide level. This review aims to give an overview of the different methods available to date for the detection of citrullinated proteins and peptides. These include 2D-SDS PAGE and immunodetection, as well as specific mass spectrometry (MS) approaches, both labeled and unlabeled. These MS approaches have been developed to pinpoint the exact location of citrullination on the peptide level. Improving the currently existing detection strategies while focusing on the role of citrullinated proteins will be invaluable to elucidate the importance of this posttranslational modification in vivo. PMID- 22318878 TI - Antioxidant and antimicrobial potentials of Serbian red wines produced from international Vitis vinifera grape varieties. AB - BACKGROUND: Antioxidant and antimicrobial potentials of Serbian red wines produced from different international Vitis vinifera grape varieties and their correlation with contents of phenolic compounds were studied by spectrophotometric and chromatographic methods. The antioxidant activity of red wines was estimated through their ability to scavenge 2,2'-diphenyl-1 picrylhydrazyl free radical (DPPH(*) ). The red wines, gallic acid, (+)-catechin and quercetin were screened in vitro for antimicrobial activity against Gram positive and Gram-negative strains using microdilution and disc diffusion techniques. RESULTS: Excellent correlations between the contents of quercetin-3 glucoside (R(2) = 0.9463) and quercetin (R(2) = 0.9337) and DPPH(*) -scavenging ability of the red wines were found. Serbian red wines exhibited significant activity against Staphylococcus aureus, Listeria inocua, Micrococcus flavus, Sarcina lutea, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis and Shigella sonnei strains, which was in correlation with their phenolic composition and antioxidant activity. The compounds gallic acid, quercetin and (+)-catechin showed high activity against B. subtilis, S. aureus, S. lutea and M. flavus Gram-positive and S. enteritidis and P. aeruginosa Gram negative strains. CONCLUSION: The results show that quercetin-3-glucoside and quercetin concentrations can be used as markers for the determination of antioxidant and antimicrobial potentials of red wines. PMID- 22318879 TI - Factors associated with antiretroviral medication adherence among HIV-positive adults accessing highly active antiretroviral therapy (HAART) in British Columbia, Canada. AB - BACKGROUND: Among those accessing treatment, highly active antiretroviral therapy (HAART) has transformed HIV into a chronic and manageable condition. However, high levels of adherence are required to derive a sustained, long-term clinical benefit. The aim of this study was to examine the predictors of adherence based on prescription refill among persons on HAART in British Columbia, Canada. METHODS: This study utilizes data collected between July 2007 and January 2010, as part of the Longitudinal Investigations into Supportive and Ancillary health services (LISA) cohort, which is a study of HIV-positive persons who have accessed antiretroviral therapy (ART) in British Columbia. Participants were considered optimally adherent if they were dispensed >=95% of their prescribed antiretrovirals. RESULTS: Of a total of 566 participants, only 316 (55.8%) were optimally adherent to HAART. Independent predictors of optimal adherence were increasing age (adjusted odds ratio [AOR] = 1.84, 95% confidence interval [CI]: 1.44-2.33), male gender (AOR = 1.68, 95% CI: 1.07-2.64), and being enrolled in a comprehensive adherence assistance program (AOR = 4.26, 95% CI: 2.12-8.54). Having an annual income <$15 000 (AOR = 0.47, 95% CI: 0.31-0.72) and both former and current injection drug use (AOR = 0.46, 95% CI: 0.29-0.73 and AOR = 0.35, 95% CI: 0.20-0.58, respectively) were independently associated with suboptimal (<95%) adherence. CONCLUSIONS: We found that women and people who inject drugs are at increased risk of being suboptimally adherent to HAART. Optimal adherence remains a significant public health and clinical goal in the context of rapidly expanding access to HAART. PMID- 22318880 TI - Hormonal and experiential predictors of infant survivorship and maternal behavior in a monogamous primate (Callicebus cupreus). AB - To better understand the roles that hormones and experience play in infant survival and maternal behavior in a biparental primate species, we analyzed urinary estrone (E(1)C) and pregnanediol glucuronide (PdG) from 24 socially housed titi monkey (Callicebus cupreus) females over 54 pregnancies (N = 1,430 samples). Pregnancies were categorized according to whether the infant survived (N = 35) or not (N = 19), and by maternal parity (primiparous: N = 9; multiparous: N = 45). Mothers of infants that survived had a significantly greater drop in PdG from the third trimester to the first week postpartum than mothers of infants that did not survive. Multiparous mothers had a greater increase in PdG from the first to the third trimester as well as greater increases in the E(1)C:PdG ratio from the first to the third trimester and from the third trimester to the first week postpartum. There were positive relationships between third trimester PdG and maternal carrying and nursing during the first week postpartum, and between maternal age and carrying during the infant's first month of life. There was a negative correlation between maternal age and PdG during the third trimester. These results suggest that elevated progesterone during late pregnancy followed by progesterone withdrawal immediately following parturition is associated with greater probability of infant survivorship and maternal behavior in this species, and that older females engage in more postpartum maternal care. PMID- 22318881 TI - Empiric pacemaker compared with a monitoring strategy in patients with syncope and bifascicular conduction block--rationale and design of the Syncope: Pacing or Recording in ThE Later Years (SPRITELY) study. AB - AIM: This study seeks to identify the optimal management strategy for patients with syncope in the context of bifascicular block and preserved left ventricular systolic function. METHODS AND RESULTS: This multicentre, randomized, open label, parallel group pragmatic randomized trial will test the hypothesis that a strategy of empiric permanent pacemaker implantation in patients with syncope and bifascicular heart block improves future outcome more effectively than a strategy of therapy guided by prolonged monitoring with an implantable loop recorder (ILR). A total of 120 patients with bifascicular block, preserved left ventricular function, and >= 1 syncopal spell in the preceding year will be randomized to receive a permanent pacemaker or ILR in at least 20 centres in Canada, the USA, Asia, and Europe. The primary outcome measure will be a composite of Major Adverse Study-Related Events (MASRE) in a 2-year observation period, wherein the events are death, syncope, symptomatic bradycardia, asymptomatic diagnostic bradycardia, and acute and chronic device complications. Prespecified secondary endpoints will include syncope symptoms, quality of life, and economic burden. CONCLUSION: This trial will provide high-level and generalizable evidence for the use of either permanent pacing or implantable loop recorders as a first line intervention for patients with syncope, preserved systolic function, and bifascicular block. PMID- 22318882 TI - Density functional theory calculation of cyclic carboxylic phosphorus mixed anhydrides as possible intermediates in biochemical reactions: implications for the Pro-Tide approach. AB - Cyclic acyl phosphoramidates (CAPAs) are important components in several fundamental biological reactions such as protein synthesis and phosphorylation. These structures are particularly interesting in the nucleotide pro-drug approach, Pro-Tide, since they are putative intermediates in one of the hydrolysis steps required for activation. The central role played by the amino acid carboxylate function suggests first the formation of a cyclic mixed phosphorus anhydride, rapidly followed by water attack. To investigate such speculations, we performed quantum mechanical calculations using the B3LYP/6 311+G** level of theory for the plausible mechanisms of action considered. In the five-membered ring case, transition state theory demonstrated how the overall, gas-phase, mechanism of action could be split into two in-line addition elimination (A-E) steps separated by a penta-coordinate phosphorane intermediate. The difference between five-membered and six-membered ring first A-E was also explored, revealing a single step, unimolecular reaction for the six-membered ring A-E profile. Implicit solvent contribution further confirmed the importance of CAPAs as reactive intermediates in such kind of reactions. Lastly, the second A-E pathway was analyzed to understand the complete pathway of the reaction. This analysis is the first attempt to clarify the putative mechanism of action involved in the activation of Pro-Tides and casts light also on the possible mechanism of action involved in primordial protein syntheses, strengthening the hypothesis of a common cyclic mixed phosphorus anhydride species as a common intermediate. PMID- 22318883 TI - Sulfur-tolerant redox-reversible anode material for direct hydrocarbon solid oxide fuel cells. AB - A novel composite anode material consisting of K(2) NiF(4) -type structured Pr(0.8) Sr(1.2) (Co,Fe)(0.8) Nb(0.2) O(4+delta) (K-PSCFN) matrix with homogenously dispersed nano-sized Co-Fe alloy (CFA) has been obtained by annealing perovskite Pr(0.4) Sr(0.6) Co(0.2) Fe(0.7) Nb(0.1) O(3-delta) (P-PSCFN) in H(2) at 900 degrees C. The K-PSCFN-CFA composite anode is redox-reversible and has demonstrated similar catalytic activity to Ni-based cermet anode, excellent sulfur tolerance, remarkable coking resistance and robust redox cyclability. PMID- 22318884 TI - Diabetes and cancer: the mechanistic implications of epidemiological analyses from the Hong Kong Diabetes Registry. AB - Diabetes is a disorder of energy metabolism associated with increased cancer risk, but the underlying mechanism is poorly understood. In a prospective cohort of patients enrolled in the Hong Kong Diabetes Registry, we explored risk factors for cancer including drug usage in type 2 diabetes. In a series of published papers, we reported a linear risk association of cancer with glycated haemoglobin with a threshold at 6.0%-6.5% and non-linear risk associations of body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride and white blood cell (WBC) count in V-shaped or A-shaped manners. Detailed pharmacoepidemiological analysis revealed markedly attenuated cancer risk in patients treated with insulin and oral anti-diabetic drugs compared with non-users of these drugs. We further observed significant drug-subphenotype interactions with attenuated cancer risk in metformin users with low high-density lipoprotein cholesterol, renin-angiotensin system (RAS) inhibitor users with high WBC count and statin users with co-presence of low low-density lipoprotein cholesterol plus albuminuria or low triglyceride. These novel observations corroborate with experimental findings of possible consequences of hyperglycaemia on dysregulation of cholesterol metabolism, renin-angiotensin system and adenosine 5'-monophosphate-activated protein kinase pathways, all of which may be implicated in carcinogenesis. On the basis of these epidemiological and experimental findings, we argue for the strong need to strengthen the health care system to ensure that type 2 diabetes subjects receive appropriate drugs to optimize internal milieu to reduce all events including cancer. Apart from mechanistic studies, large-scale, randomized clinical trials using medications such as statin, renin-angiotensin system inhibitors and metformin in patients with risk-conferring subphenotypes are needed to confirm their anti-cancer effects. PMID- 22318885 TI - Gelation on heating of supercooled gelatin solutions. AB - Diluted (1.0-1.5 wt%) aqueous gelatin solutions have been cooled to -10 degrees C at a cooling rate 20 degrees C min(-1) without freezing and detectable gelation. When heated at a constant heating rate (0.5 -2 degrees C min(-1)), the obtained supercooled solutions demonstrate an atypical process of gelation that has been characterized by regular and stochastically modulated differential scanning calorimetry (DSC) as well as by isoconversional kinetic analysis. The process is detectable as an exothermic peak in the total heat flow of regular DSC and in the nonreversing heat flow of stochastically modulated DSC. Isoconversional kinetic analysis applied to DSC data reveals that the effective activation energy of the process increases from approximately 75 to 200 kJ mol( 1) as a supercooled solution transforms to gel on continuous heating. PMID- 22318886 TI - Variability and relationship among Mixolab and Falling Number evaluation based on influence of fungal alpha-amylase addition. AB - BACKGROUND: In bread-making technology, alpha-amylase activity is routinely measured with a Falling Number device to predict wheat flour quality. The aim of this study was to determine the possibility of using Mixolab parameters to assess the Falling Number (FN) index. The effects of different doses of fungal alpha amylase addition on the Mixolab characteristics and FN index values were investigated. RESULTS: Principal component analysis was performed in order to illustrate the relationships between the Mixolab parameters and the FN index. To highlight the linear combination between the FN index values and the Mixolab parameters used to evaluate starch pasting properties (C3, C4, C5 and point differences C34 and C54), a multivariate prediction model was developed. Greatest precision (R = 0.728) was obtained for the linear regression FN = f(C4, C54) model. This model was tested on a different sample set than the one on which it was built. A high correlation was obtained between predictive model and measured FN index values (r = 0.896, P = 0.01). CONCLUSION: The model provides a framework to predict the evolution of the FN index, which is predicted by the torque for cooking stability (C4) and the difference between points C5 and C4 (C54). The obtained results suggested that the Mixolab device could be a reliable instrument for evaluation of the FN index values. PMID- 22318887 TI - PASSEL: the PeptideAtlas SRMexperiment library. AB - Public repositories for proteomics data have accelerated proteomics research by enabling more efficient cross-analyses of datasets, supporting the creation of protein and peptide compendia of experimental results, supporting the development and testing of new software tools, and facilitating the manuscript review process. The repositories available to date have been designed to accommodate either shotgun experiments or generic proteomic data files. Here, we describe a new kind of proteomic data repository for the collection and representation of data from selected reaction monitoring (SRM) measurements. The PeptideAtlas SRM Experiment Library (PASSEL) allows researchers to easily submit proteomic data sets generated by SRM. The raw data are automatically processed in a uniform manner and the results are stored in a database, where they may be downloaded or browsed via a web interface that includes a chromatogram viewer. PASSELenables cross-analysis of SRMdata, supports optimization of SRMdata collection, and facilitates the review process of SRMdata. Further, PASSELwill help in the assessment of proteotypic peptide performance in a wide array of samples containing the same peptide, as well as across multiple experimental protocols. PMID- 22318888 TI - Juggling priorities: female mating tactics in Phayre's leaf monkeys. AB - Extended sexual receptivity in primates is thought to facilitate paternity confusion, thus decreasing the risk of infanticide. However, females might also provide some indication of ovulation to attract preferred males during fertile periods. We examined female mate preferences across defined receptive periods (N = 59) in a group of wild Phayre's leaf monkeys (Trachypithecus phayrei crepusculus) at Phu Khieo Wildlife Sanctuary (February-September 2006; 2,603 contact hours). The group contained seven cycling adult females and three reproductively active males (one adult and two adolescents). We predicted that females would prefer the adult male during periovulatory (POP) receptive periods, but the adolescent males during nonperiovulatory (NPOP) and postconceptive (PC) periods. We collected focal and ad libitum data on sexual and agonistic behaviors to determine female preferences and male awareness of female fertility. We also determined the degree of mating overlap to assess if males were capable of monopolizing females. Our results indicate that females were more frequently proceptive and receptive toward the adult male during POP. By contrast, females were more proceptive and receptive toward one of the adolescent males during PC periods, but rarely interacted with the other adolescent. Patterns of attractivity and agonism across receptive periods suggested that the adult male could detect fertility, while the preferred adolescent could not. Finally, we found a high degree of overlap in total receptive period days, but a low degree of overlap in POP receptive days, suggesting that the adult male might have monopolized females, especially since he seemed to be aware of female fertility. Although these results suggest that females provide some information on ovulation, they also suggest that females attempt to confuse paternity, perhaps capitalizing on male differences in the ability to detect fertility. PMID- 22318889 TI - A [Fe(CB6)] platform for binding of small molecules: insights from DFT calculations. AB - The viability of making [Fe(CB(6))L] (L = H(2), N(2), O(2), nitric oxide [NO(-), NO, and NO(+)], CO(2), and hydrocarbons [CH(4), C(2)H(6), C(2)H(4), and C(6)H(6)]) has been investigated by density functional theory (DFT) calculations. The complexes 2-18 are thermodynamically stable and may be synthesized. The small molecules are activated to some extent after complexation. Molecular orbital and DeltaG calculation revealed that the molecular hydrogen and hydrocarbons can be chemically adsorbed and desorbed on [Fe(CB(6))] without any significant chemical modification and therefore [Fe(CB(6))] may serve as a storage material. The N(2), O(2), and nitric oxide (NO(-), NO, and NO(+)) can be activated using [Fe(CB(6))]. Proton, carbon, boron, and nitrogen NMR chemical shift calculation predicts drastic chemical shift difference before and after the complexation of [Fe(CB(6))] with small molecules. This new findings suggest that the CB(6)(2-) ligand-based complex may provide several applications in the future. PMID- 22318890 TI - Epiphytic lichens and lichenicolous fungi from the northern part of Montenegro. AB - A list of 120 taxa of lichens (117 species) and three species of lichenicolous fungi from the northern part of Montenegro is presented. The lichens Biatora chrysantha, Caloplaca monacensis, Candelariella efflorescens, Loxospora elatina, Micarea adnata, Ochrolechia arborea, O. microstictoides, Phaeophyscia nigricans, Physconia enteroxantha, Ph. grisea, Rinodina capensis, R. polysporoides, R. pyrina, Scoliciosporum umbrinum var. corticolum, Xanthoria candelaria, X. ulophyllodes and the lichenicolous fungi Lichenodiplis lecanorae, Telogalla olivieri, and Xanthoriicola physciae are new to Montenegro. PMID- 22318891 TI - Combination studies of Eucalyptus torelliana F. Muell. leaf extracts and clarithromycin on Helicobacter pylori. AB - Helicobacter pylori is a Gram-negative bacillus that is associated with the development of gastritis and peptic ulcer disease (PUD). In Nigeria, leaf extracts of Eucalyptus torelliana F. Muell. are used in traditional medicine to treat PUD and other gastrointestinal ailments. The additive and synergistic effects of E. torelliana leaf extracts, in combination with clarithromycin, were investigated using two types of H. pylori strains (ATCC 43629, ATCC 43579) and four clinical isolates of H. pylori (Ed, A2, G1-1, 5514) in the checkerboard assay and the fractional inhibitory concentration (FIC) index. A time-kill study was also performed on the strain ATCC 43579. The results showed that the E. torelliana extract inhibited the growth of all H. pylori strains, and the addition of one of the isolated active compounds, namely compound 2 (a substituted pyrenyl ester) enhanced the activity of clarithromycin. The minimum inhibitory concentration values of clarithromycin and the botanical compound were reduced twofold (from 0.125 to 0.0625 ug/mL and > 100 to 50 ug/mL respectively). A 100% reduction in CFU/mL of H. pylori ATCC 43579 was observed with the combination of 0.25 ug/mL clarithromycin and 100 ug/mL and 200 ug/mL compound 2 after 3 h of exposure. The results of the investigation showed that the combination of botanical compounds and antibiotics may be beneficial in the treatment of H. pylori infections. PMID- 22318893 TI - Nanomedicines based on recombinant fusion proteins for targeting therapeutic siRNA oligonucleotides. AB - The enormous promise of siRNA technology for rational and targeted therapy can only be realized if the inherent problems in terms of pharmaceutical development are overcome. Besides liposomal and polymeric nanoparticles, fusion proteins hold great potential for cell-type specific delivery of siRNA. Consisting of a protein binder and an oligonucleotide complexing domain, fusion proteins are designed for targeted delivery to a certain tissue or organ and subsequent release of the siRNA after cellular uptake. This article focuses on the possibilities and importance of targeting and complexing domains, including polymers and dendrimers. In vitro and in vivo evaluations are discussed with an in-depth view on pharmacokinetic properties. Remaining challenges concerning specificity on the tissue and molecular levels are highlighted. PMID- 22318894 TI - Heteroleptic ruthenium(II) complex-containing polymers and their bandgap tuning and photosensitizing properties. AB - A new synthetic route to novel ruthenium-containing polymers is reported. [Ru(L)(L')Cl(2)] type complexes (L and L' = bidentate N^N ligands) with a dibromo substituted ligand were polymerized by Stille cross-coupling reaction. The subsequent displacement of chloride ligands by thiocyanate was highly effective and the structures of the target polymers were fully characterized. The main chain absorption showed a significantly red-shift upon metal coordination and the metal-to-ligand charge transfer (MLCT) band of the complex enhanced the photon harvesting ability of the polymer. The extent of pi-electron delocalization of the ancillary ligands also showed interesting effects on the electronic properties of the polymers. The photosensitizing and bandgap tuning properties of these Ru(II) complexes demonstrated a new avenue to develop new classes of optoelectronic materials. PMID- 22318896 TI - Application of denaturing gradient gel electrophoresis to microbial diversity analysis in Chinese Douchi. AB - BACKGROUND: Douchi is a traditional Chinese soybean food which has been consumed for thousands years as an important protein source and flavouring ingredient. Studies have rarely been carried out to investigate its microbial composition and these are urgently required for the commercial labels and safety considerations. RESULTS: Microbial counts were statistically significant different among Douchi samples. Although the maximum diversity indexes of bacterial, bacillus and fungal polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) patterns were only 79%, 70% and 64%, some microorganisms, e.g. Bacillus subtilis, Bacillus amyloliquefaciens, Pseudomonas sp., Saccharomyces cerevisiae and Pichia farinose, were found to share dominant positions in most Douchi samples. In addition, some pathogens, e.g. Staphylococcus saprophyticus, Pantoea sp., Staphylococcus sciuri, Enterobacter sp. and Staphylococcus sp., were also identified. CONCLUSION: The PCR-DGGE technique was used for the first time as an effective method to assess the microbial communities in different Chinese Douchi samples. This information may be useful in improving the product quality, reformatting production methods, extending shelf life and scaling up the fermentation process. PMID- 22318895 TI - Inhibition of Streptococcus gordonii metabolic activity in biofilm by cranberry juice high-molecular-weight component. AB - Previous studies demonstrated that a cranberry high-molecular-mass, nondialyzable material (NDM) can inhibit adhesion of numerous species of bacteria and prevents bacterial coaggregation of bacterial pairs. Bacterial coaggregation leads to plaque formation leading to biofilm development on surfaces of oral cavity. In the present study, we evaluated the effect of low concentrations of NDM on Streptococcus gordonii metabolic activity and biofilm formation on restorative dental surfaces. We found that the NDM selectively inhibited metabolic activity of S. gordonii, without affecting bacterial viability. Inhibiting the metabolic activity of bacteria in biofilm may benefit the health of the oral cavity. PMID- 22318897 TI - Bone tissue engineering using bone marrow stromal cells and an injectable sodium alginate/gelatin scaffold. AB - To investigate the potential application of bone marrow stromal cells (BMSCs) and an injectable sodium alginate/gelatin scaffold for bone tissue engineering (BTE). The phenotype of osteogenic BMSCs was examined by mineralized nodules formation and type I collagen expression. Cell proliferation was evaluated by MTT assay. The biocompatibility of scaffold and osteogenic cells were examined by hematoxylin and eosin (H&E) staining. Ectopic bone formation as well as closure of rabbit calvarial critical-sized defects following scaffold-cell implantation were analyzed by histological examination and computed tomography (CT) scanning. Spindle-shaped osteogenic cells of high purity were derived from BMSCs. The osteogenic cells and sodium alginate/gelatin (2:3) scaffold presented fine biocompatibility following cross-linking with 0.6% of CaCl(2). After implantation, the scaffold-cell construct promoted both ectopic bone formation and bone healing in the rabbit calvarial critical-sized defect model. Our data demonstrated that the sodium alginate/gelatin scaffold could be a suitable biomaterial for bone engineering, and the scaffold-osteogenic cells construct is a promising alternative approach for the bone healing process. PMID- 22318898 TI - Trends in digestive cancer mortality, Cuba 1987-2008. AB - BACKGROUND: Gastrointestinal malignancies are among the most common cancers suffered by Cubans. The purpose of our study is to analyse the evolution of digestive cancer mortality in Cuba. METHODS: Mortality data for this study were obtained from the National Medical Records and Health Statistic Bureau. Trends (1987-2008) in age-standardized cancer mortality were described using joinpoint regression. RESULTS: In the data set of digestive cancer mortality, in the period 1987-2008, colorectal/anal cancer was the most frequent cause of cancer mortality in males and females. In men, a rise in mortality was observed for cancer of the oesophagus between 2001 and 2008, and pancreatic cancer showed a slight mortality rise for the period 1987-2008. In women, colorectal/anal cancer increased from 1989 to 2001. A mortality increase was observed for oesophageal cancer in the period 2005-08. The result of the joinpoint analysis for the age group of 35-64 years was consistent with those for overall mortality. CONCLUSION: The trend in mortality from digestive cancer in Cuba shows differences depending on sex, age and type of tumour. The Cuban health system has seen improvements in diagnostic systems, which has contributed even better diagnoses of digestive diseases. PMID- 22318900 TI - Reducing the barriers to relationships and sexuality education for persons with intellectual disabilities. AB - Opportunities for persons with intellectual disabilities to participate in relationships and sexuality education (RSE) are often constrained by the attitudes and perceptions of family carers, frontline support workers and professional staff. In order to understand how the barriers might be reduced, a study was undertaken in Northern Ireland with samples drawn from these three stakeholder groups, involving nearly 100 persons and using group and individual interviews. Although there was agreement on the need for RSE, four barriers were commonly reported: the need to protect vulnerable persons; the lack of training; the scarcity of educational resources; and cultural prohibitions. The impact of these barriers could be lessened through partnership working across these groups involving the provision of training and information about RSE, the development of risk management procedures and the empowerment of people with intellectual disabilities. PMID- 22318899 TI - Toward deciphering proteomes of formalin-fixed paraffin-embedded (FFPE) tissues. AB - Formalin-fixed paraffin-embedded (FFPE) tissue specimens comprise a potentially valuable resource for both prospective and retrospective biomarker discovery. Unlocking the proteomic profile of clinicopathological FFPE tissues is a critically essential step for annotating clinical findings and predicting biomarkers for ultimate disease prognosis and therapeutic follow-up. PMID- 22318902 TI - Long Noncoding RNAs: Insights from Biological Features and Functions to Diseases. AB - Over the past decade, genome-wide transcriptomic studies have shown that the mammalian genome is pervasively transcribed and produces many thousands of transcriptomes without bias from previous genome annotations. This finding, together with the discovery of a plethora of unexpected RNAs that have no obvious coding capacities, have challenged the traditional views that proteins are the main protagonists of cellular functions and that RNA is merely an intermediary between DNA sequence and its encoded protein. There are many different kinds of products that are generated by this pervasive transcription; this review focuses on long noncoding RNAs (lncRNAs) that have shown spatial and temporal specific patterns of expression and regulation in a wide variety of cells and tissues, adding significant complexity to the understanding of their biological roles. Recent research has shed new light onto the biological function significance of lncRNAs. Here, we review the rapidly advancing field of lncRNAs, describing their biological features and their roles in regulation of gene expression. Moreover, we highlight some recent advances in our understanding of ncRNA-mediated regulation of stem cell pluripotency, morphogenesis, and development, focusing mainly on the regulatory roles of lncRNAs. Finally, we consider the potential medical implications, and the potential use of lncRNAs in drug development and discovery and in the identification of molecular markers of diseases, including cancer. PMID- 22318903 TI - Effect of linalool on morphine tolerance and dependence in mice. AB - Linalool, a terpene alcohol, has been shown to interact with the opioid system and N-methyl-D-aspartate (NMDA) receptor. Therefore, the effect of linalool on morphine dependence and tolerance was studied. Dependence and tolerance were induced in mice using subcutaneous morphine injections, three times a day (50, 50 and 75 mg/kg /day) for 3 days. To evaluate the effect of agents on the induction of morphine dependence and tolerance, linalool (50, 75 and 100 mg/kg), clonidine (positive control), alpha-2 receptor agonist, (0.1 mg/kg), memantine, NMDA receptor antagonist (positive control), (30 mg/kg) and saline were injected intraperitoneally three times a day for 3 days. To determine the expression of morphine dependence and tolerance, all compounds were injected once intraperitoneally on the day of experiment. The effect of linalool and other agents on dependence were evaluated by counting the number of jumps (induced by naloxone 5 mg/kg). The tolerance was evaluated by the tail-flick test. The results showed that linalool in the induction and expression phase increased the nociception threshold. Linalool (48% and 95.6% at doses 75 and 100 mg/kg, respectively), clonidine and memantine reduced the severity of withdrawal signs in the induction and expression phases. This study indicated that linalool has a significant effect on morphine tolerance and dependence. This effect may be mediated partially through the inhibition of NMDA receptors. PMID- 22318901 TI - Plasma thrombospondin-1 is increased during acute sickle cell vaso-occlusive events and associated with acute chest syndrome, hydroxyurea therapy, and lower hemolytic rates. AB - Platelets are activated in sickle cell disease (SCD), and particularly during vaso-occlusive episodes (VOE). Thrombospondin-1 (TSP1), a major secretory product of activated platelets, is increased in the circulation in VOE and binds to sickle red blood cells (RBC) promoting vascular adhesion. Thus, we hypothesized that TSP1 may represent a plasma biomarker of disease severity in SCD. We tested the plasma collected from patients in steady state (n = 27) and VOE (n = 14), as well as healthy controls (n = 17) at the University of Pittsburgh Medical Center (UPMC), and from patients in steady state enrolled in the walk-PHaSST clinical trial (n = 483). We found that TSP1 levels were increased in VOE in the UPMC cohort. Among steady-state patients at UPMC, TSP1 values correlated positively with lifetime history of acute chest syndrome (r = 0.72, P < 0.0001) and hemoglobin concentration (r = 0.49, P = 0.01), and negatively with markers of hemolysis, such as LDH (r = -0.50, P = 0.009). Analysis of the walk-PHaSST cohort also showed a positive association between TSP1 levels and hydroxyurea use (r = 0.14, P = 0.003), and confirmed the negative associations with the severity of hemolysis. Our results suggest that TSP1 levels are associated with more VOE, hydroxyurea use and lower rates of hemolysis. High TSP1 concentrations may indicate higher risk of the viscosity/vaso-occlusion phenotype of SCD. PMID- 22318904 TI - Polymer nanostructures made by scanning probe lithography: recent progress in material applications. AB - Scanning probe lithography (SPL) is a series of techniques that utilizes a scanning probe or an array of probes for surface patterning. Recent developments of new material systems and patterning approaches have made SPL a promising, low cost, bench-top, and versatile tool for fabricating various polymer nanostructures, with extraordinary importance in physical sciences, life sciences and nanotechnology. This feature article highlights the recent progress in four material applications: polymer resists, polymeric carriers for patterning functional materials, electronically active polymers and polymer brushes for tailoring surface morphology and functionality. An overview of future possibilities, with regard to challenges and opportunities in this field, is given at the end of the paper. PMID- 22318905 TI - Combining Fourier transform nuclear quadrupole resonance (FT-NQR) spectroscopy and mass spectrometry (MS) to study the electronic structure of titanocene dichlorides. AB - A combination of nuclear quadrupole resonance spectroscopy (NQR) and mass spectrometry (MS) has been used to observe trends in electronic structure in three titanocenes: bis(cyclopentadienyl) titanium dichloride (eta(5) C(5)H(5))(2)TiCl(2), bis(pentamethylcyclopentadienyl) titanium dichloride (eta(5) C(5)(CH(3))(5))(2)TiCl(2) and dimethylsilylene-bridged ansa bis(cyclopentadienyl) titanium dichloride Si(CH(3))(2)(eta(5)-C(5)H(5))(2)TiCl(2). Using MS, electron ionisation mass spectra of these compounds are presented within the context of the entire homologous series with one to five methyl groups on each cyclopentadienyl ligand. A dedicated NQR spectrometer was constructed for this study with a sensitivity sufficient to precisely determine the NQR resonant frequency of (35)Cl atoms using 3 g samples of these titanocenes. The observed frequencies are thus 11.784, 11.930 and 10.863 MHz at 298 K. The results demonstrate that NQR using a relatively simple apparatus can be used as a sensitive and cost effective probe into the molecular structure of organometallic chlorides, which complements the information inferred from the mass spectra. PMID- 22318906 TI - Disruption of Staphylococcus epidermidis biofilm formation using a targeted cationic peptide. AB - This study reports the use of a targeted cationic peptide with the ability to disrupt Staphylococcus epidermidis biofilm formation. Complications due to nosocomial infections of implanted medical devices pose a significant health risk to patients, with Staphylococcus epidermidis often implicated in the case of blood-contacting biomaterials. S. epidermidis virulence relies mainly on its ability to form a biofilm, the main component of which is polysaccharide intercellular adhesin (PIA). We utilized the synthetic beta6-20 peptide, known to specifically bind S. epidermidis, in order to deliver a cationic polylysine peptide (G(3)K(6)) to the bacterial surface and disrupt the charge-charge interactions needed for PIA retention and biofilm stability. The effects of the beta6-20-G(3)K(6) peptide on biofilm formation were assessed using optical density, fluorescently labeled wheat germ agglutinin, nucleic acid stain (SYTO 9), and a metabolic assay (XTT, 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H tetrazolium-5-carboxanilide inner salt). Biofilms formed in the presence of beta6 20-G(3)K(6) peptide (100 MUM) resulted in a 37.9% reduction in PIA content and a 17.5% reduction of adherent bacteria relative to biofilms grown in the absence of peptide. These studies demonstrate the targeting ability of the beta6-20 peptide towards biomaterial-adherent S. epidermidis, and highlight the potential for disrupting the early stages of biofilm formation. PMID- 22318907 TI - Combined effect of electrical stimulation, aging time and marination on quality of chicken breast fillet processed under commercial conditions. AB - BACKGROUND: Electrical stimulation (ES) in poultry processing is reported in the literature with varying degrees of effectiveness. Furthermore, the combined effects of ES and polyphosphate marination are not completely known. The objective of this study was to evaluate the combined effect of ES, aging time prior to deboning and phosphate marination on meat quality of broiler breast fillets. RESULTS: The implementation of ES accelerated pH decline in fillets at any aging time studied regardless of marination treatment, but no differences (P > 0.05) were found in pH of fillets deboned without aging. Warner-Bratzler (WB) shear values of ES fillets significantly decreased (P < 0.05) at 2 h of aging whereas WB of non-ES fillets decreased at 6 h of aging in breast meat, with or without marination. In non-marinated fillets the ES treatment reduced (P < 0.05) cooking loss in meat aged 0, 2 and 4 h. In marinated fillets the ES treatment decreased cooking loss at 2, 4, 6 and 8 h of aging. CONCLUSION: ES in carcasses aged 2 or 4 h improves tenderness and reduces cooking loss. Marination improves tenderness in both stimulated and non-stimulated fillets, at all aging times. PMID- 22318908 TI - Genetic variants within ultraconserved elements and susceptibility to right- and left-sided colorectal adenocarcinoma. AB - We investigated whether single nucleotide polymorphisms within ultraconserved elements (UCEs) are associated with susceptibility to overall colorectal cancer (CRC) and susceptibility to tumor site-specific CRC. The study included 787 CRC patients and 551 healthy controls. The study comprised of a training set (520 cases and 341 controls) and a replication set (267 cases and 210 controls). We observed associations in rs7849 and rs1399685 with CRC risk. For example, a dose dependent trend (per-allele odds ratio (OR), 0.78; 95% confidence interval (CI), 0.63-1.00; P for trend = 0.05) associated with the variant allele of rs7849 in the training set. The significant trend toward a decrease in CRC risk was confirmed in the replication set (per-allele OR, 0.72; 95% CI, 0.52-0.99; P for trend = 0.044). When stratified by tumor location, for left-sided CRC (LCRC) risk, significant association was observed for the variant-containing genotypes of rs1399685 (OR, 1.77; 95% CI, 1.02-3.06) and the risk was replicated in the replication population (OR, 2.04; 95% CI, 1.02-4.07). The variant genotypes of rs9784100 and rs7849 conferred decreased risk but the associations were not replicated. Three right-sided CRC (RCRC) susceptibility loci were identified in rs6124509, rs4243289 and rs12218935 but none of the loci was replicated. Joint effects and potential higher order gene-gene interactions among significant variants further categorized patients into different risk groups. Our results strongly suggest that several genetic variants in the UCEs may contribute to CRC susceptibility, individually and jointly, and that different genetic etiology may be involved in RCRC and LCRC. PMID- 22318909 TI - Leukocyte telomere length predicts overall survival in hepatocellular carcinoma treated with transarterial chemoembolization. AB - Previous studies have reported that telomere length in peripheral blood leukocytes can predict the clinical outcome of several cancers. However, whether leukocyte telomere length is associated with the prognosis of hepatocellular carcinoma (HCC) remains to be determined. In this study, relative telomere length (RTL) in peripheral blood leukocytes was measured using a real-time PCR-based method for 269 HCC patients treated with transarterial chemoembolization (TACE) from two independent hospitals. The association between RTL and the overall survival (OS) of HCC was analyzed. The immunological function of the HCC patients with different leukocyte RTLs was evaluated. Multivariate analyses indicated that long leukocyte RTL was significantly associated with poor OS of HCC patients, with a hazard ratio of 2.04 (95% confidence interval, 1.46-2.86; P < 0.001). Kaplan-Meier analyses showed a significant difference of median survival time between patients with long and short RTL (log rank P < 0.001). Fluorescence activated cell sorting analyses showed that the long RTL group had a significantly increased percentage of CD4(+)CD25(+)FOXP3(+) Treg in CD4(+) T cells compared with short RTL group (P = 0.002). In conclusion, our results suggest that leukocyte RTL may serve as an independent prognostic marker for HCC patients treated with TACE. PMID- 22318910 TI - Internal anatomy and ultrastructure of the male reproductive system of the Norway lobster Nephrops norvegicus (Decapoda: Astacidea). AB - The Norway lobster (Nephrops norvegicus) is economically important in Europe. However, apart from the female reproductive system, very little is known about its internal anatomy. This article focuses on studying the internal anatomy and ultrastructure of the male reproductive system. This system follows the general pattern found among decapod crustaceans, with several peculiarities. Testes are composed of lobular sperm ducts in which the spermatozoa are fully constituted. The spermatozoa present three lateral arms and a long acrosome, which gives a false appearance of flagellated spermatozoa. The two testes form a double H under the heart, and the vas deferens (VD) arise from each side at the posterior edge of the double H. The main characteristic of the VD is the presence of a sphincter in the enlarged area of the distal end of the middle VD. The MVD here shows an increase in musculature of the wall as compared to the VD, which regulates the passage of the sperm cord to the distal VD (DVD) and thence to the thelycum of the female. The wall of the spermatophore is formed in the distal part of the proximal VD, which surrounds the unique sperm cord present in the VD. Isolated spermatophores are not observed in the VD. The sperm cord is pinched off during copulation by the musculature of the DVD. Then, a portion of the sperm cord is transferred from each VD to form the isolated spermatophores. The wall of the spematophores and the spermatozoa that are observed inside the thelycum have the same morphology as those observed in the VD. PMID- 22318911 TI - Hydroxysafflor yellow A attenuates lymphostatic encephalopathy-induced brain injury in rats. AB - Hydroxysafflor yellow A (HSYA) is a main chemical component of the flower of Carthamus tinctorius. The present study investigated whether HSYA could attenuate brain injury induced by lymphostatic encephalopathy (LE). This was induced in adult male Wistar rats by cervical lymphatic blockade (CLB). Heart rate variability (HRV) was used as an indirect measurement of the regulatory function of the autonomic nervous system by recording the ECG signals from rats. It was shown that treatment with HSYA (5 mg/kg, i.p.) significantly alleviated the neurological deficits observed in rats with LE. Histological staining revealed that HSYA treatment attenuated LE-induced cell apoptosis in the rostral ventrolateral medullus (RVLM). Animals in the LE groups exhibited impaired regulatory roles of the autonomic nervous system in cardiovascular function, which was suppressed by pretreatment with HSYA. Additionally, HSYA administration significantly prevented the decrease of endothelial nitric oxide synthase (eNOS) mRNA and protein expression in the RVLM of rats with LE. These findings suggest that HSYA might provide neuroprotection against LE-induced brain injury and the associated functional alterations, which is likely regulated by the nitric oxide pathway. PMID- 22318912 TI - Anisotropic ionic mobility of lithium salts in lamellar liquid crystalline polymer networks. AB - New mesogens presenting smectic A (SmA) phases and capable of hosting lithium salts are designed. The mesogens comprise a vinyl-functionalized spacer to allow further reaction to the polymer backbone, an aromatic core and ethylene oxide chains, able to coordinate lithium ions. Copolymerizing these monomers with a suitable crosslinker yields the first lithium containing liquid crystalline elastomers (LCEs). The SmA structure where the ethylene oxide chains are microphase separated in layers is fixed by the crosslinking and permanent macroscopic orientation is obtained. Diffusion and conductivity measurements of the monomer sample show a large anisotropy of the ion mobility (100 for the cation and 400 for the anion). In the elastomer the anisotropy of the lithium mobility is comparable to that in the monomers. PMID- 22318913 TI - Lichens from the Una National Park (Bosnia and Herzegovina). AB - A list of 57 taxa of lichens (56 species) from the Una National Park in the north western part of Bosnia and Herzegovina is presented. Bacidia subincompta, Buellia griseovirens, Candelariella reflexa, Cetrelia monachorum, Fulgensia subbacteata, Lecanora subcarpinea, L. subrugosa, and Trapeliopsis viridescens are new for Bosnia and Herzegovina. PMID- 22318915 TI - The association between pharmacologic drug intoxication and forensic-specific intent. AB - Two criminal cases are presented in which the counsel for the defendants requested an expert witness to opine whether their drug-intoxicated clients were capable of forming the specific intent necessary to commit the felonies for which they were charged. Intent from a legal standpoint is often times a poorly understood concept among expert witnesses. The application of a criminal defense of intoxication depends upon the nature of the crime the defendant is accused. The intoxication defense cannot be applied to general intent crimes. In cases where specific intent crimes are charged against the defendant, voluntary intoxication may be used to prove that the defendant could not possess the capacity to formulate the intent as a necessary element of the crime. Voluntary intoxication may be used as a defense in specific intent crimes to negate the critical element of intent required for the prosecution to prove in criminal cases. Without being able to prove intent, the prosecution has not met their burden of proving that every element of the crime has been met, thus resulting in an acquittal. PMID- 22318914 TI - An fMRI investigation of responses to peer rejection in adolescents with autism spectrum disorders. AB - Peer rejection is particularly pervasive among adolescents with autism spectrum disorders (ASD). However, how adolescents with ASD differ from typically developing adolescents in their responses to peer rejection is poorly understood. The goal of the current investigation was to examine neural responses to peer exclusion among adolescents with ASD compared to typically developing adolescents. Nineteen adolescents with ASD and 17 typically developing controls underwent fMRI as they were ostensibly excluded by peers during an online game called Cyberball. Afterwards, participants reported their distress about the exclusion. Compared to typically developing adolescents, those with ASD displayed less activity in regions previously linked with the distressing aspect of peer exclusion, including the subgenual anterior cingulate and anterior insula, as well as less activity in regions previously linked with the regulation of distress responses during peer exclusion, including the ventrolateral prefrontal cortex and ventral striatum. Interestingly, however, both groups self-reported equivalent levels of distress. This suggests that adolescents with ASD may engage in differential processing of social experiences at the neural level, but be equally aware of, and concerned about, peer rejection. Overall, these findings contribute new insights about how this population may differentially experience negative social events in their daily lives. PMID- 22318916 TI - Thailand's Work and Health Transition. AB - Thailand has experienced a rapid economic transition from agriculture to industry and services, and from informal to formal employment. It has much less state regulation and worker representation relative to developed nations, who underwent these transitions more slowly and sequentially, decades earlier. We examine the strengthening of Thai government policy and legislation affecting worker's health, responding to international norms, a new democratic constitution, fear of foreign importer embargos and several fatal workplace disasters. We identify key challenges remaining for Thai policy makers, including legislation enforcement and the measurement of impacts on worker's mental and physical health. PMID- 22318917 TI - FTIR microscopy of biological cells and tissue: data analysis using resonant Mie scattering (RMieS) EMSC algorithm. AB - Transmission and transflection infrared microscopy of biological cells and tissue suffer from significant baseline distortions due to scattering effects, predominantly resonant Mie scattering (RMieS). This scattering can also distort peak shapes and apparent peak positions making interpretation difficult and often unreliable. A correction algorithm, the resonant Mie scattering extended multiplicative signal correction (RMieS-EMSC), has been developed that can be used to remove these distortions. The correction algorithm has two key user defined parameters that influence the accuracy of the correction. The first is the number of iterations used to obtain the best outcome. The second is the choice of the initial reference spectrum required for the fitting procedure. The choice of these parameters influences computational time. This is not a major concern when correcting individual spectra or small data sets of a few hundred spectra but becomes much more significant when correcting spectra from infrared images obtained using large focal plane array detectors which may contain tens of thousands of spectra. In this paper we show that, classification of images from tissue can be achieved easily with a few (<10) iterations but a reliable interpretation of the biochemical differences between classes could require more iterations. Regarding the choice of reference spectrum, it is apparent that the more similar it is to the pure absorption spectrum of the sample, the fewer iterations required to obtain an accurate corrected spectrum. Importantly however, we show that using three different non-ideal reference spectra, the same unique correction solution can be obtained. PMID- 22318918 TI - General shame and bodily shame in eating disorders: a 2.5-year longitudinal study. AB - OBJECTIVE: Studies have established a link between shame and eating disorder symptoms but have generally been cross-sectional or failed to differentiate between general shame and bodily shame. The present study addressed both these issues. DESIGN: This study used a longitudinal panel design. METHOD: Fifty-five women with a past or current eating disorder participated. They completed measures of eating pathology, depression, general shame (internal and external) and bodily shame (current feelings of bodily shame as well as bodily shame that is anticipated were the individual to gain weight) and were followed up over 2.5 years. RESULTS: Bodily shame uniquely predicted an increase in anorexic (but not bulimic) symptoms. Current bodily shame predicted an increase in the degree of underweight and the misperception of body size. Anticipated bodily shame predicted an increase in fear of weight gain. DISCUSSION: Current versus anticipated bodily shame predicts different anorexic symptoms. Both therefore should be considered in developing interventions and aetiological models of anorexia nervosa. PMID- 22318919 TI - Collagen scaffolds derived from fresh water fish origin and their biocompatibility. AB - Collagen, a major component of native extracellular matrix, has diverse biomedical applications. However, its application is limited due to lack of cost effective production and risk of disease transmission from bovine sources currently utilized. This study describes fabrication and characterization of nano/micro fibrous scaffolds utilizing collagen extracted from fresh water fish origin. This is the first time collagen extracted from fresh water fish origin was studied for their biocompatibility and immunogenicity. The nano/micro fibrous collagen scaffolds were fabricated through self-assembly owing to its amphiphilic nature and were subsequently cross-linked. In vitro degradation study revealed higher stability of the cross-linked scaffolds with only ~50% reduction of mass in 30 days, while the uncross-linked one degraded completely in 4 days. Further, minimal inflammatory response was observed when collagen solution was injected in mice with or without adjuvant, without significant dilution of sera. The fish collagen scaffolds exhibited considerable cell viability and were comparable with that of bovine collagen. SEM and fluorescence microscopic analysis revealed significant proliferation rate of cells on the scaffolds and within 5 days the cells were fully confluent. These findings indicated that fish collagen scaffolds derived from fresh water origin were highly biocompatible in nature. PMID- 22318921 TI - Meat fatty acid and cholesterol level of free-range broilers fed on grasshoppers on alpine rangeland in the Tibetan Plateau. AB - BACKGROUND: Meat safety and nutrition are major concerns of consumers. The development of distinctive poultry production methods based on locally available natural resources is important. Grasshoppers are rich in important nutrients and occur in dense concentrations in most rangelands of northern China. Foraging chickens could be used to suppress grasshopper infestations. However, knowledge of the fatty acid content of meat from free-range broilers reared on alpine rangeland is required. RESULTS: Rearing conditions and diet did not significantly (P > 0.05) affect concentrations of saturated fatty acid (SFA), arachidonic acid, docosahexaenoic acid or the ratio of total n-6 to total n-3 fatty acids. Breast muscle of chickens that had consumed grasshoppers contained significantly (P < 0.05) less monounsaturated fatty acid, but the ratio of polyunsaturated fatty acids (PUFA)/SFA and contents of total n-3, total n-6 and PUFA were significantly (P > 0.05) higher than intensively reared birds. Compared with meat from intensively reared birds, meat from free-range broilers had less cholesterol and higher concentrations of total lipid and phospholipids. CONCLUSION: Chickens eating grasshoppers in rangeland produce superior quality meat and reduce the grasshopper populations that damage the pastures. This provides an economic system of enhanced poultry-meat production, which derives benefits from natural resources rather than artificial additives. PMID- 22318920 TI - Fibronectin is essential for survival but is dispensable for proliferation of hepatocytes in acute liver injury in mice. AB - Acute liver injury causes massive hepatocyte apoptosis and/or fatal liver damage. Fibronectin, an extracellular matrix glycoprotein, is prominently expressed during adult tissue repair. However, the extent of fibronectin dependence on hepatocyte response to acute liver damage remains to be defined. Because identification of hepatic survival factors is critical for successful therapeutic intervention in liver failure, this relationship has been investigated using a fibronectin-deficient mouse model of acute liver injury. Here, we show that lack of fibronectin induces significantly increased hepatocyte apoptosis, which is accompanied by significant down-regulation of the antiapoptotic protein, B-cell lymphoma-extra large (Bcl-xL). Furthermore, fibronectin deficiency leads to a significantly elevated production of hepatocyte growth factor in hepatic stellate cells postinjury, which, in turn, results in an earlier onset and acceleration of hepatocyte regeneration. Primary hepatocytes on fibronectin are protected from reactive oxygen species-induced cellular damage, retaining the expression of Bcl xL, whereas those on type I collagen are not. This retained expression of Bcl-xL is inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. CONCLUSION: We provide evidence that fibronectin-mediated matrix survival signals for hepatocytes are transduced through the PI3K/Bcl-xL-signaling axis in response to injury. This work defines fibronectin as a novel antiapoptotic factor for hepatocytes after acute liver injury, but demonstrates that fibronectin is not essential for subsequent hepatocyte proliferation. PMID- 22318923 TI - Ginseng as a potential novel addition to the antikeloid weaponry. AB - Keloid scars are large protruding claw-shaped lesions that develop beyond the confines of the wound and uniquely appears only in humans. For thousands of years ginseng has been used in the traditional medicine in oriental countries. It occupies a prominent position in the list of the best-selling medicinal herbs in the world. Panax ginseng often called Asian or Korean ginseng, is the most extensively used and the best grade of ginseng and the term of 'ginseng' generally refers to Panax ginseng. Previous studies have revealed that ginseng inhibits NF-kappa B, TGF-beta, IL-6, ACE and MMP-2 and these factors play a pivotal role in keloid formation pathogenesis. Therefore it could be reasoned that ginseng could be effective for the treatment of the keloid scars. Clinical studies by topical applications of iPanax notoginseng (800 ug/ml) are warranted. PMID- 22318922 TI - Catalytic diastereoselective tandem conjugate addition-elimination reaction of Morita-Baylis-Hillman C adducts by C-C bond cleavage. AB - Through the cleavage of the C-C bond, the first catalytic tandem conjugate addition-elimination reaction of Morita-Baylis-Hillman C adducts has been presented. Various S(N)2'-like C-, S-, and P-allylic compounds could be obtained with exclusive E configuration in good to excellent yields. The Michael product could also be easily prepared by tuning the beta-C-substituent group of the alpha methylene ester under the same reaction conditions. Calculated relative energies of various transition states by DFT methods strongly support the observed chemoselectivity and diastereoselectivity. PMID- 22318924 TI - Thermal and photochemical crosslinking of hyperbranched polyphenylene with organic azides. AB - Here, we report on the first example of crosslinking (CL) hyperbranched polyphenylene (hb-PPh) with a small molecule crosslinker 1,3,5 tris(azidomethyl)benzene (TAMB). It was successfully shown that CL of the hb PPh/TAMB (9:1) film is possible either thermally or photochemically making use of fundamentally different reaction mechanisms. Starting from a model reaction to prove the feasibility of the thermal CL reaction, we went on to check both the thermal and the photochemical crosslinkability of micrometer thick films. IR spectroscopy was furthermore used to confirm the CL process. Finally, the thin film morphology of the films before and after CL was investigated by AFM, revealing that the surface morphology was unaffected by the CL processes. PMID- 22318925 TI - Quinoa starch granules: a candidate for stabilising food-grade Pickering emulsions. AB - BACKGROUND: Particle-stabilised emulsions, so-called Pickering emulsions, are known to possess many beneficial properties, including being extremely stable. Starch granules isolated from quinoa have been used as emulsion stabilising particles. The granules were intact, 1-3 um in diameter and modified with octenyl succinic anhydride to increase their hydrophobicity. Starch granules, as opposed to most other particles used to generate Pickering emulsions, are edible, abundant and derived from natural sources. RESULTS: Emulsions produced by high shear homogenisation had droplet sizes of 9-70 um depending on the starch-to-oil ratio. Droplet size decreased with increasing starch-to-oil ratio, but was unaffected by the oil phase volume over a range of 5-33% oil (v/v). Although the drops were large and subject to creaming, their size remained unchanged over a period of 7 days. By adjusting the starch-to-oil ratio drops could be made to be buoyancy neutral to prevent creaming. Rheological characterisation indicated a gel structure with an elastic modulus in the range 200-2000 Pa depending on droplet size. CONCLUSION: This work has demonstrated the successful use of starch granules to stabilise emulsions which may find applications beyond that of food, for example in cosmetics and pharmaceutical formulations. PMID- 22318926 TI - Hepatitis C virus selectively perturbs the distal cholesterol synthesis pathway in a genotype-specific manner. AB - Hepatitis C virus (HCV) subverts host cholesterol metabolism for key processes in its lifecycle. How this interference results in the frequently observed, genotype dependent clinical sequelae of hypocholesterolemia, hepatic steatosis, and insulin resistance (IR) remains incompletely understood. Hypocholesterolemia typically resolves after sustained viral response (SVR), implicating viral interference in host lipid metabolism. Using a targeted cholesterol metabolomic platform we evaluated paired HCV genotype 2 (G2) and G3 patient sera for changes in in vivo HCV sterol pathway metabolites. We compared HCV genotypic differences in baseline metabolites and following antiviral treatment to assess whether sterol perturbation resolved after HCV eradication. We linked these metabolites to IR and urine oxidative stress markers. In paired sera from HCV G2 (n = 13) and G3 (n = 20) patients, baseline sterol levels were lower in G3 than G2 for distal metabolites (7-dehyrocholesterol (7DHC) 0.017 versus 0.023 mg/dL; P(adj) = 0.0524, cholesterol 140.9 versus 178.7 mg/dL; P(adj) = 0.0242) but not the proximal metabolite lanosterol. In HCV G3, SVR resulted in increased levels of distal metabolites (cholesterol [Delta55.2 mg/dL; P(adj) = 0.0015], 7DHC [Delta0.0075 mg/dL; P(adj) = 0.0026], lathosterol [Delta0.0430 mg/dL P(adj) = 0.0405]). In contrast, lanosterol was unchanged after SVR (P = 0.9515). CONCLUSION: HCV G3, but not G2, selectively interferes with the late cholesterol synthesis pathway, evidenced by lower distal sterol metabolites and preserved lanosterol levels. This distal interference resolves with SVR. Normal lanosterol levels provide a signal for the continued proteolysis of 3-hydroxyl-3 methylglutaryl coenzyme A reductase, which may undermine other host responses to increase cholesterol synthesis. These data may provide a hypothesis to explain why hypocholesterolemia persists in chronic HCV infection, particularly in HCV G3, and is not overcome by host cholesterol compensatory mechanisms. PMID- 22318927 TI - Cooperative hierarchical self-assembly of peptide dendrimers and linear polypeptides into nanoarchitectures mimicking viral capsids. PMID- 22318928 TI - A pilot study evaluating multiple risk factor interventions by community pharmacists to prevent cardiovascular disease: the PAART CVD pilot project. AB - BACKGROUND: There is insufficient evidence for the efficacy of comprehensive multiple risk factor interventions by pharmacists in the primary prevention of cardiovascular disease (CVD). Given the proven benefits of pharmacist interventions for individual risk factors, it is essential that evidence for a comprehensive approach to care be generated so that pharmacists remain key members of the health care team for individuals at risk of initial onset of CVD. OBJECTIVE: To establish the feasibility of an intervention delivered by community pharmacists to reduce the risk of primary onset of CVD. METHODS: A single-cohort intervention study was undertaken in 2008-2009. Twelve community pharmacists from 10 pharmacies who were trained to provide lifestyle and medicine management support to reduce CVD risk recruited 70 at-risk participants aged 50-74 years who were free from diabetes or CVD. Participants received a baseline assessment to establish CVD risk and health behaviors. An assessment report provided to patients and pharmacists was used to collaboratively establish treatment goals and, over 5 sessions, implement treatment strategies. Follow-up assessment at 6 months measured changes in baseline parameters. The primary outcome was the average change to overall 5-year risk of CVD onset. RESULTS: Sixty-seven participants were included in the analysis. The mean participant age was 60 years and 73% were female. We observed a 25% (95% CI 17 to 33) proportional risk reduction in overall CVD risk. Significant reductions also occurred in mean blood pressure (-11/-5 mm Hg) and waist circumference (-1.3 cm), with trends toward improvement for most other observed risk factors. CONCLUSIONS: Findings support previous evidence of positive cardiovascular health outcomes following pharmacist intervention in other patient groups; we recommend generating randomized controlled trial evidence for a primary prevention population. PMID- 22318929 TI - Assessment of prescribers' knowledge of the cost of medications. AB - BACKGROUND: In 2003, the World Health Organization reported that 50% of patients are adherent to long-term therapies. Frequently, the reason for a patient's nonadherence is the cost of medications. Even with prescription insurance coverage, patients may not be able to afford their medications. OBJECTIVE: To assess prescriber knowledge of the cost of commonly prescribed medications including atorvastatin, gabapentin, levofloxacin, losartan, pantoprazole, pioglitazone, and quetiapine. Secondary objectives were to evaluate how often prescribers consult a discounted drug list and a patient's prescription insurance coverage. METHODOLOGY: One hundred prescribers from the Medical University of South Carolina were surveyed from November 2010 to January 2011. Prescribers consisted of medical residents, attending physicians, fellows, nurse practitioners, and physician assistants. Wholesale prices of medications were determined using the Red Book, and prescription insurance prices were calculated from an average of the top 3 prescription insurance companies' copayments. RESULTS: Medical residents made up 72% of those surveyed, fellows 3%, attending physicians 12%, physician assistants 3%, and nurse practitioners 10%. The prescriber groups were unable to correctly determine the cost of medications of more than 50% of total possible responses. The majority of prescribers rarely asked about a patient's prescription insurance coverage or consulted a discounted drug list before writing a prescription. CONCLUSIONS: Prescribers are more likely to know the cost of medications for patients who have prescription insurance coverage versus those who do not. PMID- 22318930 TI - Fidaxomicin for the treatment of Clostridium difficile infections. AB - OBJECTIVE: To evaluate the pharmacology, microbiology, safety, and efficacy of fidaxomicin for treatment of Clostridium difficile infections (CDI). DATA SOURCES: Literature was identified through Ovid MEDLINE (1948-December 2011) and International Pharmaceutical Abstracts (1970-December 2011) using the search terms fidaxomicin, OPT-80, PAR-101, OP-118, difimicin, tiacumicin, lipiarmycin, Clostridium difficile, Clostridium difficile infection, Clostridium difficile associated diarrhea, and cost. Drug monographs were retrieved from manufacturers' Web pages, and the Red Book component of Micromedex was used for cost information. STUDY SELECTION AND DATA EXTRACTION: All pertinent Phase 1, 2, and 3 studies published in English were included. DATA SYNTHESIS: Fidaxomicin is a macrocyclic compound bactericidal against C. difficile and inhibits toxin and spore production. It has poor oral absorption with high fecal concentrations. Available Phase 2 and 3 data with fidaxomicin 200 mg orally every 12 hours demonstrate similar effectiveness in treating CDI compared to oral vancomycin. Fidaxomicin was shown to have less frequency of recurrent infections. Adverse effects are uncommon and occur at similar rates as with oral vancomycin. The most frequently reported adverse effects are gastrointestinal, hematologic, and electrolyte disorders. Available data are lacking in several areas, including the efficacy and safety of fidaxomicin compared to established regimens for mild-to moderate, life-threatening, and recurrent CDIs. The cost of a 10-day course of fidaxomicin is significantly more than that of metronidazole and vancomycin for treatment of mild-to-moderate CDI. CONCLUSIONS: Fidaxomicin appears to be an effective and safe alternative to oral vancomycin for treatment of mild-to moderate and severe CDI. Data on its use compared to guideline-recommended therapies for mild-to-moderate and life-threatening CDI are needed. Further data assessing the cost-effectiveness of fidaxomicin are needed. Currently, it cannot be recommended over vancomycin for treatment of CDI. However, it may be considered for treatment of recurrent infections. PMID- 22318931 TI - Institutionalization as a risk factor for inappropriate drug use in the elderly: a Swedish nationwide register-based study. AB - BACKGROUND: Few studies have investigated institutionalization as a potential risk factor for potentially inappropriate drug use (PIDU). Sweden now has unique possibilities for comparisons of drug use in large populations of institutionalized and home-dwelling elderly through linkage of the Swedish Prescribed Drug Register (SPDR) with the Swedish Social Services Register. OBJECTIVE: To compare PIDU in institutionalized versus home-dwelling elderly persons in Sweden. METHODS: We conducted a cross-sectional retrospective study of 1,260,843 home-dwelling and 86,721 institutionalized elderly individuals. We analyzed data on age, sex, and dispensed drugs for individuals aged 65 years or older registered in the SPDR from July to September 2008. Data on type of housing were retrieved from the Social Services Register. The main outcome measures of PIDU were use of anticholinergic drugs, long-acting benzodiazepines, concurrent use of 3 or more psychotropics, and potentially serious drug-drug interactions (DDIs). RESULTS: Thirty percent of the institutionalized and 12% of the home dwelling elderly were exposed to PIDU. Living in an institution was strongly associated with overall PIDU (OR 2.36; 95% CI 2.29 to 2.44), use of anticholinergic drugs (OR 2.58; 95% CI 2.48 to 2.68), long-acting benzodiazepines (OR 1.50; 95% CI 1.41 to 1.60), and concurrent use of 3 or more psychotropics (OR 7.26; 95% CI 6.96 to 7.59), after controlling for age, sex, and number of drugs (used as proxy for comorbidity). However, institutionalization was associated with a lower probability of potentially serious DDIs (OR 0.60; 95% CI 0.55 to 0.65). CONCLUSIONS: Our results indicate that institutionalization is a potential risk factor for PIDU. This implies that more cautious prescribing is warranted in institutions, where the frailest and most vulnerable elderly individuals reside. Research is needed to identify underlying risk factors for PIDU within these settings. PMID- 22318932 TI - Pharmacology, efficacy, and safety of linagliptin for the treatment of type 2 diabetes mellitus. AB - OBJECTIVE: To review the pharmacology, pharmacokinetics, and clinical efficacy and safety of linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor recently approved in the US for use as a treatment for type 2 diabetes mellitus. DATA SOURCES: English-language articles in the PubMed database to October 2011 (selected using the search terms linagliptin, alogliptin, sitagliptin, saxagliptin, vildagliptin, and pharmacokinetics, pharmacodynamics, or diabetes) were identified for review. Reference lists from identified articles were reviewed for additional references of interest. Abstracts published at relevant meetings were also evaluated, and information was obtained from the manufacturer. STUDY SELECTION AND DATA EXTRACTION: Publications reporting the pharmacology, pharmacokinetics, and clinical efficacy and safety of linagliptin were reviewed. DATA SYNTHESIS: Linagliptin therapy results in clinically meaningful reductions in hemoglobin A(1c), as well as fasting and postprandial plasma glucose levels in patients with type 2 diabetes mellitus. It contrasts with other agents in its class by not requiring dosage adjustment in patients with renal or hepatic impairment. Oral doses of linagliptin 5 mg once daily have been shown to be clinically effective, well tolerated, and weight-neutral. An increased rate of hypoglycemia when linagliptin was used in combination with an insulin secretagogue compared to placebo was noted in clinical trials. CONCLUSIONS: Linagliptin provides an additional therapeutic option for type 2 diabetes mellitus and, in contrast to other agents in the DPP-4 class, can be used without dose adjustment in patients with any degree of declining renal function. PMID- 22318934 TI - Osteoblast activity on carbonated hydroxyapatite. AB - Hydroxyapatite (HA), has been used commonly as a bone substitute and as a scaffold in bone tissue engineering. However it has certain drawbacks such as limited biodegradability and osteointegration properties. Other forms of HA, for example, carbonated hydroxyapatite (CHA) could prove to have enhanced bioactivity as they more closely mimic the chemical composition of the apatite found in human bone. The aim of this study was to test the efficacy of CHA in comparison to HA used as a control. The CHA (4.9 wt %) and the HA discs were seeded with MC3T3-E1 osteoblastic cells. Results revealed a trend of increased cell attachment on the HA discs at day 0, however, the cell proliferation on the CHA discs at 7 and 28 days showed no significant difference in comparison to the HA control. SEM of the CHA discs showed surface irregularities at 7 days indicating dissolution. Also at 7 days, SEM demonstrated cell attachment and extracellular matrix production on both the CHA and HA samples. There was no significant difference in the total amount of collagen produced in the CHA samples relative to the HA control samples at 28 days as evaluated by the hydroxyproline assay. Real time PCR revealed mRNA increase by 2.08, 7.62, and 9.86 fold for collagen I a1, collagen III a1, and osteocalcin respectively on the CHA as compared to the HA discs. This study demonstrates the use of CHA as a biocompatible material that has potentially increased biodegradation properties and osteogenic capability in comparison to HA. PMID- 22318935 TI - The radiative decay rates tune the emissive properties of ruthenium(II) polypyridyl complexes: a computational study. PMID- 22318936 TI - Adjuvant early and late cardioprotective therapy: access to the heart. AB - Coronary heart disease is still the leading cause of death in industrialized nations, occurring either as acute coronary occlusion and myocardial infarction or as chronic ischaemic cardiomyopathy caused by continuous obstruction of one or more coronary arteries. Even after successful reperfusion, an additional loss of otherwise vital cardiomyocytes may occur in the primary ischaemic area, called lethal reperfusion injury. In experimental settings, delivery of therapeutic agents targeting the reperfusion injury reduces the infarct size by 30%. In addition to the choice of therapeutic agent and time point, the mode of application may be crucial for the therapeutic success. Therefore, this review focuses on the current and future administration techniques for early and late post-myocardial infarction therapies. PMID- 22318937 TI - Review focus on the role of microRNA in cardiovascular biology and disease. PMID- 22318938 TI - A novel triterpene extract from mistletoe induces rapid apoptosis in murine B16.F10 melanoma cells. AB - The European mistletoe Viscum album L. is a plant used for remedies in cancer treatment. The benefit of commonly used aqueous extracts is controversial but the plant contains water insoluble triterpene acids providing interesting anticancer properties. Triterpene extracts (TE) from plants and single triterpenoids such as oleanolic acid (OA) or betulinic acid (BA) are known for their cytotoxic effects on cancer cell lines in vitro. We report here cytotoxic effects of a novel OA rich triterpene extract from mistletoe (V. album L., Santalaceae) solubilized by 2-hydroxypropyl-beta-cyclodextrin (2-HP-beta-CD) on B16.F10 mouse melanoma cells. The 2-HP-beta-CD solubilized triterpene extract (STE) was highly cytotoxic by causing DNA fragmentation, followed by loss of membrane integrity and intracellular adenosine-5'-triphosphate (ATP). Blocking the caspase machinery by inhibitors aborted DNA fragmentation and delayed the cytotoxic effects but did not prevent cell death. The solubilization by 2-HP-beta-CD allows a solvent-free application of triterpene extracts in the in vitro setting. These findings suggest the use of STE from mistletoe as a solvent-free anticancer drug for preclinical animal experiments and clinical trials. PMID- 22318939 TI - Synthesis of beta-cyclodextrin containing copolymer via "click" chemistry and its self-assembly in the presence of guest compounds. AB - We report the synthesis of a hydrophilic copolymer with one polyethylene glycol (PEG) block and one beta-cyclodextrin (beta-CD) containing block by a "click" reaction between azido-substituted beta-CD and propargyl flanking copolymer. (1)H NMR study suggested a highly efficient conjugation of beta-CD units by this approach. The obtained copolymer was used as a host macromolecule to construct assemblies in the presence of hydrophobic guests. For assemblies containing a hydrophobic polymer, their size can be simply adjusted by simply changing the content of hydrophobic component. By serving as a guest molecule, hydrophobic drugs can also be loaded accompanying the formation of nanoparticles, and the drug payload is releasable. Therefore, the copolymer synthesized herein can be employed as a carrier for drug delivery. PMID- 22318940 TI - Screening of the antioxidant properties and polyphenol composition of aromatised green tea infusions. AB - BACKGROUND: Aromatised green teas are widely sold and popular owing to their fragrance. In this study the antioxidant activity of six commercial green tea infusions was assessed by three complementary assays. RESULTS: In order to evaluate the tea infusions as antioxidant sources, their phenolic content (Folin Ciocalteu assay), cupric ion-reducing antioxidant capacity (CUPRAC) and 2,2 diphenyl-1-picryhydrazyl (DPPH) radical-scavenging ability were determined. Their content of polyphenols was also determined by high-performance liquid chromatography/mass spectrometry (HPLC/MS) in negative electrospray ionisation mode. Some teas with citrus aroma, besides having a relatively high content of catechins, also contain other phenolic compounds such as naringin and hesperidin. The three assays used to evaluate the antioxidant capacity of the tea infusions gave different rank orders. Therefore an antioxidant index was calculated for better correlation of the results, and its highest value was obtained for Clear Green Mint tea infusion. CONCLUSION: The studied teas, besides having a relatively high content of catechins, also contain naringin and hesperidin, which are not present in 'pure' green tea. It is important to run multiple assays to get a better estimate of the antioxidant capacity of a given sample. PMID- 22318941 TI - Stat3-mediated activation of microRNA-23a suppresses gluconeogenesis in hepatocellular carcinoma by down-regulating glucose-6-phosphatase and peroxisome proliferator-activated receptor gamma, coactivator 1 alpha. AB - Considerable effort has been made in elucidating the mechanism and functional significance of high levels of aerobic glycolysis in cancer cells, commonly referred to as the Warburg effect. Here we investigated whether the gluconeogenic pathway is significantly modulated in hepatocarcinogenesis, resulting in altered levels of glucose homeostasis. To test this possibility, we used a mouse model (mice fed a choline-deficient diet) that develops nonalcoholic steatohepatitis (NASH), preneoplastic nodules, and hepatocellular carcinoma (HCC), along with human primary HCCs and HCC cells. This study demonstrated marked reduction in the expressions of G6pc, Pepck, and Fbp1 encoding the key gluconeogenic enzymes glucose-6-phosphatase, phosphoenolpyruvate carboxykinase, fructose-1,6 phosphatase, respectively, and the transcription factor Pgc-1alpha in HCCs developed in the mouse model that correlated with reduction in serum glucose in tumor-bearing mice. The messenger RNA (mRNA) levels of these genes were also reduced by ~80% in the majority of primary human HCCs compared with matching peritumoral livers. The expression of microRNA (miR)-23a, a candidate miR targeting PGC-1alpha and G6PC, was up-regulated in the mouse liver tumors as well as in primary human HCC. We confirmed PGC-1alpha and G6PC as direct targets of miR-23a and their expressions negatively correlated with miR-23a expression in human HCCs. G6PC expression also correlated with tumor grade in human primary HCCs. Finally, this study showed that the activation of interleukin (IL)-6-Stat3 signaling caused the up-regulation of miR-23a expression in HCC. CONCLUSION: Based on these data, we conclude that gluconeogenesis is severely compromised in HCC by IL6-Stat3-mediated activation of miR-23a, which directly targets PGC 1alpha and G6PC, leading to decreased glucose production. PMID- 22318942 TI - Multifunctional ferromagnetic carbon-nanotube arrays prepared by pulse-injection chemical vapor deposition. PMID- 22318943 TI - An imidazolium-based fluorescent cyclophane for the selective recognition of iodide. PMID- 22318944 TI - Age-dependent renal cortical microvascular loss in female mice. AB - Renal function and blood flow decline during aging in association with a decrease in the number of intrarenal vessels, but if loss of estrogen contributes to this microvascular, rarefaction remains unclear. We tested the hypothesis that the decreased renal microvascular density with age is aggravated by loss of estrogen. Six-month-old female C57/BL6 mice underwent ovariectomy (Ovx) or sham operation and then were allowed to age to 18-22 mo. Another comparable group was replenished with estrogen after Ovx (Ovx+E), while a 6-mo-old group served as young controls. Kidneys were then dissected for evaluation of microvascular density (by micro-computed tomography) and angiogenic and fibrogenic factors. Cortical density of small microvessels (20-200 MUm) was decreased in all aged groups compared with young controls (30.3 +/- 5.8 vessels/mm2, P < 0.05), but tended to be lower in sham compared with Ovx and Ovx+E (9.9 +/- 1.7 vs. 17.2 +/- 4.2 and 18 +/- 3.0 vessels/mm2, P = 0.08 and P = 0.02, respectively). Cortical density of larger microvessels (200-500 MUm) decreased only in aged sham (P = 0.04 vs. young control), and proangiogenic signaling was attenuated. On the other hand, renal fibrogenic mechanisms were aggravated in aged Ovx compared with aged sham, but blunted in Ovx+E, in association with downregulated transforming growth factor-beta signaling and decreased oxidative stress in the kidney. Therefore, aging induced in female mice renal cortical microvascular loss, which was likely not mediated by loss of endogenous estrogen. However, estrogen may play a role in protecting the kidney by decreasing oxidative stress and attenuating mechanisms linked to renal interstitial fibrosis. PMID- 22318945 TI - Deficiency of lymphotoxin-alpha does not exacerbate high-fat diet-induced obesity but does enhance inflammation in mice. AB - Lymphotoxin-alpha (LTalpha) is secreted by lymphocytes and acts through tumor necrosis factor-alpha receptors and the LTbeta receptor. Our goals were to determine whether LT has a role in obesity and investigate whether LT contributes to the link between obesity and adipose tissue lymphocyte accumulation. LT deficient (LT(-/-)) and wild-type (WT) mice were fed standard pelleted rodent chow or a high-fat/high-sucrose diet (HFHS) for 13 wk. Body weight, body composition, and food intake were measured. Glucose tolerance was assessed. Systemic and adipose tissue inflammatory statuses were evaluated by quantifying plasma adipokine levels and tissue macrophage and T cell-specific gene expression in abdominal fat. LT(-/-) mice were smaller (20%) and leaner (25%) than WT controls after 13 wk of HFHS diet feeding. LT(-/-) mice showed improved glucose tolerance, suggesting that, in WT mice, LT may impair glucose metabolism. Surprisingly, adipose tissue from rodent chow- and HFHS-fed LT(-/-) mice exhibited increased T lymphocyte and macrophage infiltration compared with WT mice. Despite the fact that LT(-/-) mice exhibited an enhanced inflammatory status at the systemic and tissue level even when fed rodent chow, they were protected from enhanced diet-induced obesity and insulin resistance. Thus, LT contributes to body weight and adiposity and is required to modulate the accumulation of immune cells in adipose tissue. PMID- 22318946 TI - Mass spectrometry for the molecular imaging of angiotensin metabolism in kidney. AB - To better understand the tissue distribution and activity of enzymes involved in angiotensin II (Ang II) processing, we developed a novel molecular imaging method using matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. Mouse kidney sections (12 MUm) were incubated with 10-1,000 MUmol/l Ang II for 5-15 min at 37 degrees C. The formed peptides Ang III and Ang-(1-7) were identified by MALDI-TOF/TOF. A third metabolite, Ang-(1-4), was generated from further degradation of Ang-(1-7). Enzymatic processing of Ang II was dose and time dependent and absent in heat-treated kidney sections. Distinct spatial distribution patterns (pseudocolor images) were observed for the peptides. Ang III was localized in renal medulla, whereas Ang-(1-7)/Ang-(1-4) was present in cortex. Regional specific peptide formation was confirmed using microdissected cortical and medullary biopsies. In vitro studies with recombinant enzymes confirmed activity of peptidases known to generate Ang III or Ang-(1-7) from Ang II: aminopeptidase A (APA), Ang-converting enzyme 2 (ACE2), prolyl carboxypeptidase (PCP), and prolyl endopeptidase (PEP). Renal medullary Ang III generation was blocked by APA inhibitor glutamate phosphonate. The ACE2 inhibitor MLN-4760 and PCP/PEP inhibitor Z-pro-prolinal reduced cortical Ang-(1-7) formation. Our results establish the power of MALDI imaging as a highly specific and information-rich analytical technique that will further aid our understanding of the role and site of Ang II processing in cardiovascular and renal pathologies. PMID- 22318947 TI - The phosphodiesterases type 5 inhibitor tadalafil reduces the activation of the hypothalamus-pituitary-adrenal axis in men during cycle ergometric exercise. AB - Phosphodiesterase type 5 inhibitors may influence human physiology, health, and performance by also modulating endocrine pathways. We evaluated the effects of a 2-day tadalafil administration on adenohypophyseal and adrenal hormone adaptation to exercise in humans. Fourteen healthy males were included in a double-blind crossover trial. Each volunteer randomly received two tablets of placebo or tadalafil (20 mg/day with a 36-h interval) before a maximal exercise was performed. After a 2-wk washout, the volunteers were crossed over. Blood samples were collected at -30 and -15 min and immediately before exercise, immediately after, and during recovery (+15, +30, +60, and +90 min) for adrenocorticotropin (ACTH), beta-endorphin, growth hormone (GH), prolactin, cortisol (C), corticosterone, dehydroepiandrosterone-sulfate (DHEAS), and cortisol binding globulin (CBG) assays. C-to-CBG (free cortisol index, FCI) and DHEAS-to-C ratios were calculated. Exercise intensity, perceived exertion rate, O2 consumption, and CO2 and blood lactate concentration were evaluated. ACTH, GH, C, corticosterone, and CBG absolute concentrations and/or areas under the curve (AUC) increased after exercise after both placebo and tadalafil. Exercise increased DHEAS only after placebo. Compared with placebo, tadalafil administration reduced the ACTH, C, corticosterone, and FCI responses to exercise and was associated with higher beta-endorphin AUC and DHEAS-to-C ratio during recovery, without influencing cardiorespiratory and performance parameters. Tadalafil reduced the activation of the hypothalamus-pituitary-adrenal axis during exercise by probably influencing the brain's nitric oxide- and cGMP-mediated pathways. Further studies are necessary to confirm our results and to identify the involved mechanisms, possible health risks, and potential clinical uses. PMID- 22318948 TI - Enhanced effect of daytime restricted feeding on the circadian rhythm of streptozotocin-induced type 2 diabetic rats. AB - There is increasing awareness of the link between impaired circadian clocks and multiple metabolic diseases. However, the impairment of the circadian clock by type 2 diabetes has not been fully elucidated. To understand whether and how the function of circadian clock is impaired under the diabetic condition, we examined not only the expression of circadian genes in the heart and pineal gland but also the behavioral rhythm of type 2 diabetic and control rats in both the nighttime restricted feeding (NRF) and daytime restricted feeding (DRF) conditions. In the NRF condition, the circadian expression of clock genes in the heart and pineal gland was conserved in the diabetic rats, being similar to that in the control rats. DRF shifted the circadian phases of peripheral clock genes more efficiently in the diabetic rats than those in the control rats. Moreover, the activity rhythm of rats in the diabetic group was completely shifted from the dark phase to the light phase after 5 days of DRF treatment, whereas the activity rhythm of rats in the control group was still under the control of the suprachiasmatic nucleus (SCN) after the same DRF treatment. Furthermore, the serum glucose rhythm of type 2 diabetic rats was also shifted and controlled by the external feeding schedule, ignoring the SCN rhythm. Therefore, DRF shows stronger effect on the reentrainment of circadian rhythm in the type 2 diabetic rats, suggesting that the circadian system in diabetes is unstable and more easily shifted by feeding stimuli. PMID- 22318949 TI - Hypothalamic Fkbp51 is induced by fasting, and elevated hypothalamic expression promotes obese phenotypes. AB - To discover hypothalamic genes that might play a role in regulating energy balance, we carried out a microarray screen for genes induced by a 48-h fast in male C57Bl/6J mouse hypothalamus. One such gene was Fkbp51 (FK506 binding protein 5; Locus NP_034350). The product of this gene is of interest because it blocks glucocorticoid action, suggesting that fasting-induced elevation of this gene in the hypothalamus may reduce glucocorticoid negative feedback, leading to elevated glucocorticoid levels, thus promoting obese phenotypes. Subsequent analysis demonstrated that a 48-h fast induces Fkbp51 in ventromedial, paraventricular, and arcuate hypothalamic nuclei of mice and rats. To assess if hypothalamic Fkbp51 promotes obesity, the gene was transferred to the hypothalamus via an adeno-associated virus vector. Within 2 wk following Fkbp51 overexpression, mice on a high-fat diet exhibited elevated body weight, without hyperphagia, relative to mice receiving the control mCherry vector. Body weight remained elevated for more than 8 wk and was associated with elevated corticosterone and impaired glucose tolerance. These studies suggest that elevated hypothalamic Fkbp51 promotes obese phenotypes. PMID- 22318950 TI - Mammary gland serotonin regulates parathyroid hormone-related protein and other bone-related signals. AB - Breast cells drive bone demineralization during lactation and metastatic cancers. A shared mechanism among these physiological and pathological states is endocrine secretion of parathyroid hormone-related protein (PTHrP), which acts through osteoblasts to stimulate osteoclastic bone demineralization. The regulation of PTHrP has not been accounted for fully by any conventional mammotropic stimuli or tumor growth factors. Serotonin (5-HT) synthesis within breast epithelial cells is induced during lactation and in advancing breast cancer. Here we report that serotonin deficiency (knockout of tryptophan hydroxylase-1) results in a reduction of mammary PTHrP expression during lactation, which is rescued by restoring 5-HT synthesis. 5-HT induced PTHrP expression in lactogen-primed mammary epithelial cells from either mouse or cow. In human breast cancer cells 5 HT induced both PTHrP and the metastasis-associated transcription factor Runx2/Cbfa1. Based on receptor expression and pharmacological evidence, the 5-HT2 receptor type was implicated as being critical for induction of PTHrP and Runx2. These results connect 5-HT synthesis to the induction of bone-regulating factors in the normal mammary gland and in breast cancer cells. PMID- 22318951 TI - Lack of myostatin alters intermyofibrillar mitochondria activity, unbalances redox status, and impairs tolerance to chronic repetitive contractions in muscle. AB - Loss of myostatin (mstn) function leads to a decrease in mitochondrial content, a reduced expression of cytochrome c oxidase, and a lower citrate synthase activity in skeletal muscle. These data suggest functional or ultrastructural mitochondrial abnormalities that can impact on muscle endurance characteristics in such phenotype. To address this issue, we investigated subsarcolemmal and intermyofibrillar (IMF) mitochondrial activities, skeletal muscle redox homeostasis, and muscle fiber endurance quality in mstn-deficient mice [mstn knockout (KO)]. We report that lack of mstn induced a decrease in the coupling of IMF mitochondria respiration, with significantly higher basal oxygen consumption. No lysis of mitochondrial cristae or excessive swelling were observed in mstn KO mice compared with wild-type (WT) mice. Concerning redox status, mstn KO gastrocnemius exhibited a significant decrease in lipid peroxidation levels ( 56%; P < 0.01 vs. WT) together with a significant upregulation of the antioxidant glutathione system. In contrast, superoxide dismutase and catalase activities were altered in mstn KO, gastrocnemius and soleus with a reduction of up to 80% compared with WT animals. The force production observed after contractile endurance test was significantly lower in extensor digitorum longus and soleus muscles of mstn KO mice compared with the controls (17 +/- 3 and 36 +/- 5% vs. 28 +/- 4 and 56 +/- 5%, respectively, P < 0.05). Together, these findings indicate that, besides an increased skeletal muscle mass, genetic mstn inhibition has differential effects on redox homeostasis and mitochondrial function that would have functional consequences on muscle response to endurance exercise. PMID- 22318952 TI - Thr649Ala-AS160 knock-in mutation does not impair contraction/AICAR-induced glucose transport in mouse muscle. AB - AS160 and its closely related protein TBC1D1 have emerged as key mediators for both insulin- and contraction-stimulated muscle glucose uptake through regulating GLUT4 trafficking. Insulin increases AS160 phosphorylation at multiple Akt/PKB consensus sites, including Thr(649), and promotes its binding to 14-3-3 proteins through phospho-Thr(649). We recently provided genetic evidence that AS160 Thr(649) phosphorylation/14-3-3 binding plays a key role in mediating insulin stimulated glucose uptake in muscle. Contraction has also been proposed to increase phosphorylation of AS160 and TBC1D1 via AMPK, which could be detected by a generic phospho-Akt substrate (PAS) antibody. Here, analysis of AS160 immunoprecipitates from muscle extracts with site-specific phospho-antibodies revealed that contraction and AICAR caused no increase but rather a slight decrease in phosphorylation of the major PAS recognition site AS160-Thr(649). In line with this, contraction failed to enhance 14-3-3 binding to AS160. Consistent with previous reports, we also observed that in situ contraction stimulated the signal intensity of PAS antibody immunoreactive protein of ~150-160 kDa in muscle extracts. Using a TBC1D1 deletion mutant mouse, we showed that TBC1D1 protein accounted for the majority of the PAS antibody immunoreactive signals of ~150-160 kDa in extracts of contracted muscles. Consistent with the proposed role of AS160 Thr(649) phosphorylation/14-3-3 binding in mediating glucose uptake, AS160 Thr(649)Ala knock-in mice displayed normal glucose uptake upon contraction and AICAR in isolated muscles. We conclude that the previously reported PAS antibody immunoreactive band ~150-160 kDa, which were increased upon contraction, does not represent AS160 but TBC1D1, and that AS160-Thr(649)Ala substitution impairs insulin- but neither contraction- nor AICAR-stimulated glucose uptake in mouse skeletal muscle. PMID- 22318953 TI - Update on adipose tissue blood flow regulation. AB - According to Fick's principle, any metabolic or hormonal exchange through a given tissue depends on the product of the blood flow to that tissue and the arteriovenous difference. The proper function of adipose tissue relies on adequate adipose tissue blood flow (ATBF), which determines the influx and efflux of metabolites as well as regulatory endocrine signals. Adequate functioning of adipose tissue in intermediary metabolism requires finely tuned perfusion. Because metabolic and vascular processes are so tightly interconnected, any disruption in one will necessarily impact the other. Although altered ATBF is one consequence of expanding fat tissue, it may also aggravate the negative impacts of obesity on the body's metabolic milieu. This review attempts to summarize the current state of knowledge on adipose tissue vascular bed behavior under physiological conditions and the various factors that contribute to its regulation as well as the possible participation of altered ATBF in the pathophysiology of metabolic syndrome. PMID- 22318954 TI - A new transgenic rat model overexpressing the angiotensin II type 2 receptor provides evidence for inhibition of cell proliferation in the outer adrenal cortex. AB - This study aimed to elucidate the role of the AT(2) receptor (AT(2)R), which is expressed and upregulated in the adrenal zona glomerulosa (ZG) under conditions of increased aldosterone production. We developed a novel transgenic rat (TGR; TGRCXmAT(2)R) that overexpresses the AT(2)R in the adrenal gland, heart, kidney, brain, skeletal muscle, testes, lung, spleen, aorta, and vein. As a consequence the total angiotensin II (Ang II) binding sites increased 7.8-fold in the kidney, 25-fold in the heart, and twofold in the adrenals. The AT(2)R number amounted to 82-98% of total Ang II binding sites. In the ZG of TGRCXmAT(2)R, the AT(2)R density was elevated threefold relative to wild-type (WT) littermates, whereas AT(1)R density remained unchanged. TGRCXmAT(2)R rats were viable and exhibited normal reproduction, blood pressure, and kidney function. Notably, a slightly but significantly reduced body weight and a moderate increase in plasma urea were observed. With respect to adrenal function, 24-h urinary and plasma aldosterone concentrations were unaffected in TGRCXmAT(2)R at baseline. Three and 14 days of Ang II infusion (300 ng.min(-1).kg(-1)) increased plasma aldosterone levels in WT and in TGR. These changes were completely abolished by the AT(1)R blocker losartan. Of note, glomerulosa cell proliferation, as indicated by the number of Ki-67-positive glomerulosa cells, was stimulated by Ang II in TGR and WT rats; however, this increase was significantly attenuated in TGR overexpressing the AT(2)R. In conclusion, AT(2)R in the adrenal ZG inhibits Ang II-induced cell proliferation but has no obvious lasting effect on the regulation of the aldosterone production at the investigated stages. PMID- 22318955 TI - Rise and fall of oral health products with Canadian bloodroot extract. AB - The rhizome of Sanguinaria canadensis (SC, bloodroot) contains an active principle with antimicrobial, antiinflammatory, antioxidative and immunomodulatory effects. For this reason SC extract has been added to toothpastes and mouthwashes in various concentrations. When tested separately, neither the toothpastes nor the mouthwashes with SC extract had any demonstrable clinical effectiveness against dental plaque and gingivitis. Although using them together twice a day seemed more effective than using placebo, more recent studies have shown conflicting results. Preclinical safety studies up to 2000, which did not include studies longer than 6 months, were thought not to indicate any appreciable potential for harm - to the oral mucosa in particular. In 2003, the FDA Subcommittee on Oral Health Care Drug Products for Over-the-Counter Human Use concluded from a review that using SC-containing products is safe. However, for reasons unknown, the review failed to consider publications between 1999 and 2001 that suggested a possible link between the use of SC-containing products and the pre-neoplastic lesion, leukoplakia. As it happened, bloodroot had already been removed (in 2001) from the formula of one of the most widely used products in question and the brand has since then disappeared altogether from the worldwide market. PMID- 22318956 TI - Helical polymer as mimetic enzyme catalyzing asymmetric aldol reaction. AB - This Communication reports optically active helical substituted polyacetylenes which solely catalyzed asymmetric Aldol reaction between cyclohexanone and p nitrobenzaldehyde; more importantly the helical structures are found to play crucial roles in the asymmetric catalysis, with a remarkable yield and ee (both up to 80%). A synergic effect is observed between the helical structures in the polymer main chains and the pendent prolinamide moieties for successfully catalyzing the asymmetric reaction. The role of the helical polymer backbones is further verified by tuning the relative helical structure content. PMID- 22318957 TI - Balloon-occluded retrograde transvenous obliteration for the treatment of gastric varices. PMID- 22318964 TI - Body composition analysis in critically ill survivors: a comparison of bioelectrical impedance spectroscopy devices. AB - BACKGROUND: Body composition is commonly altered in response to critical illness and can be estimated at the bedside with bioelectrical impedance spectroscopy (BIS). Different electrode configurations may be used to mitigate assumptions of the technique, but the reliability of tetra-polar and octo-polar arrangements has yet to be established. This study aimed to compare both configurations, in a prospective observational study of 17 critically ill survivors and 12 healthy controls. METHODS: Weight, supine body length, and BIS on both tetra-polar and octo-polar configured devices were recorded, then repeated 2 days later. Bioelectrical impedance vector analysis was subsequently performed using data from the tetra-polar device at a frequency of 50 kHz. RESULTS: Test-retest agreement was acceptable for the tetra-polar device (intraclass correlation coefficient range, patients: 0.876-0.988 vs controls: 0.983-0.998, P <= 0.001). However, lower and wider ranging test-retest intraclass correlation coefficients were obtained with the octo-polar instrument in both groups. Furthermore, there was a difference in the mass/volume of body compartments measured on each device in both patients (P <= .017) and controls (P <= .045). A change in the composition profile of critically ill males was evident between measurement occasions, which was reflected by a reduction in body weight of 1.6 (1.5) kg (P <= 0.001) across the sample over the same period. CONCLUSIONS: BIS devices should not be used interchangeably in the clinical setting. The reliability of the tetra polar instrument was good, but daily fluctuations in body weight may have affected the results. PMID- 22318965 TI - Markers of inflammation and coagulation may be modulated by enteral feeding strategy. AB - BACKGROUND: Although enteral nutrition (EN) is provided to most mechanically ventilated patients, the effect of specific feeding strategies on circulating markers of coagulation and inflammation is unknown. METHODS: Markers of inflammation (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, interferon [IFN]-gamma, IL-6, IL-8, IL-10, IL-12) and coagulation (tissue factor [TF], plasminogen activator inhibitor-1) were measured at baseline (n = 185) and 6 days (n = 103) in mechanically ventilated intensive care unit patients enrolled in a randomized controlled study of trophic vs full-energy feeds to test the hypothesis that trophic enteral feeds would be associated with decreases in markers of inflammation and coagulation compared to full-energy feeds. RESULTS: There were no differences in any of the biomarkers measured at day 6 between patients who were randomized to receive trophic feeds compared to full-energy feeds. However, TF levels decreased modestly in patients from baseline to day 6 in the trophic feeding group (343.3 vs 247.8 pg/mL, P = .061) but increased slightly in the full-calorie group (314.3 vs 331.8 pg/mL). Lower levels of TF at day 6 were associated with a lower mortality, and patients who died had increasing TF levels between days 0 and 6 (median increase of 39.7) compared to decreasing TF levels in patients who lived (median decrease of 95.0, P = .033). CONCLUSIONS: EN strategy in critically ill patients with acute respiratory failure does not significantly modify inflammation and coagulation by day 6, but trophic feeds may have some modest effects in attenuating inflammation and coagulation. PMID- 22318966 TI - Fried-potato diet causes vitamin A deficiency in an autistic child. AB - A 5-year-old boy with autism developed dry eye and xerophthalmia. Serum vitamin A was undetectable. Dietary history revealed a markedly altered intake consisting of only fried potatoes and rice balls for 2 years. Fried potatoes contain no vitamin A. Autism is a multifaceted developmental disorder infrequently accompanied by abnormal eating practices. To the authors' knowledge, most children with autism who develop dietary vitamin A deficiency have consumed an excess of fried potatoes. Attention to possible vitamin A deficiency is essential when fried potatoes are consumed exclusively. PMID- 22318967 TI - Anti-inflammatory effects of beta2 adrenergic receptor agonists in experimental acute lung injury. AB - These studies were undertaken to extend emerging evidence that beta(2) adrenergic receptor (beta(2)AR) agonists, in addition to their bronchorelaxing effects, may have broad anti-inflammatory effects in the lung following onset of experimental acute lung injury (ALI). Young male C57BL/6 mice (25 g) developed ALI following airway deposition of bacterial LPS or IgG immune complexes in the absence or presence of appropriate stereoisomers (enantiomers) of beta(2)AR agonists, albuterol or formoterol. Endpoints included albumin leak into lung and buildup of polymorphonuclear neutrophils and cytokines/chemokines in bronchoalveolar fluids. Both beta(2)AR agonists suppressed lung inflammatory parameters (IC(50)=10(-7) M). Similar effects of beta(2)AR agonists on mediator release were found when mouse macrophages were stimulated in vitro with LPS. The protective effects were associated with reduced activation (phosphorylation) of JNK but not of other signaling proteins. Collectively, these data suggest that beta(2)AR agonists have broad anti-inflammatory effects in the setting of ALI. While beta(2)AR agonists suppress JNK activation, the extent to which this can explain the blunted lung inflammatory responses in the ALI models remains to be determined. PMID- 22318968 TI - New experimental data linking secondhand smoke exposure to lung cancer in nonsmokers. AB - Secondhand smoke (SHS) exposure is a known risk factor for lung cancer development in lifelong nonsmokers; however, the mechanistic involvement of SHS in the genesis of this malignancy remains elusive. The present study is the first comprehensive investigation of SHS mutagenicity in vivo, in which we have established the mutagenic effects of SHS in transgenic Big Blue mice, and subsequently found correlations between our experimental findings and those obtained from our analysis of the largest database of mutations in human TP53, which is the most frequently mutated gene in human lung cancer. We demonstrate that whole-body SHS exposure of mice for 5 h/d, 5 d/wk for a duration of 2 or 4 mo elicits a significant mutagenic response in the lung, trachea, and bladder of exposed animals, as reflected by the elevation of background cII mutant frequency in the respective organs. The organ-specific mutagenicity of SHS is most pronounced in the lung and remains persistent both in the lung and bladder of SHS exposed animals after a 1-mo recovery in clean air. The induced cII mutagenesis in the lung of SHS-exposed mice perfectly recapitulates our analysis of the TP53 mutations in human lung cancer in nonsmokers. Remarkably, the relative frequencies of all types of mutations in the TP53 gene of nonsmokers' lung tumors and in the cII transgene of lung cellular DNA from SHS-exposed mice are indistinguishable from one another. We provide the first verification of a mechanistic mode of action for SHS of relevance for carcinogenesis and the first experimental evidence linking SHS exposure to lung cancer in nonsmokers. PMID- 22318969 TI - Ortho-trifluoromethylation of functionalized aromatic triazenes. PMID- 22318970 TI - Mesenchymal stromal cells improve the osteogenic capabilities of mineralized agarose gels in a rat full-thickness cranial defect model. AB - The authors previously created HAp or CaCO(3) formed on or in agarose gels (HAp and CaCO(3) gels, respectively) as biocompatible and biodegradable bone graft materials. However, these gels have limitations for bone regeneration. Mesenchymal stromal cells (MSCs) have osteogenic potential and are considered useful for bone tissue engineering. The purpose of this study was to clarify the osteogenic abilities of MSCs loaded in HAp or CaCO(3) gels (MSC/HAp and MSC/CaCO(3) gels, respectively) using a rat cranial defect model compared to HAp and CaCO(3) gels alone. HAp, CaCO(3) , MSC/Hap, and MSC/CaCO(3) gels were prepared for in vivo analyses and implanted into full-thickness bone defects created in the rat cranium. All samples were assessed radiologically and histologically at 4 and 8 weeks after implantation. Using microfocus-computed tomography, an increase in bone formation was observed in the MSC-loaded gels compared to the gels alone. In addition, peripheral quantitative computed tomography revealed higher bone mineral contents in the MSC-loaded gels compared to the gels alone. After transmission X-ray diffraction analyses, the degree of apatite c-axis orientation as a bone quality index of newly formed bone in the MSC-loaded gels was close to that of living cranial bone. Histologically, more extensive bone formation was detected in the MSC-loaded gels compared to gels alone. Overall, MSC/HAp and MSC/CaCO(3) gels showed equivalent efficacy for bone regeneration. These findings demonstrate that loading of MSCs into the gels strengthened their osteogenic ability and improved the quality of the newly formed bone. As a result, MSC-loaded gels could represent viable therapeutic biomaterials for bone tissue engineering. PMID- 22318971 TI - Good modeling practice guidelines for applying multimedia models in chemical assessments. AB - Multimedia mass balance models of chemical fate in the environment have been used for over 3 decades in a regulatory context to assist decision making. As these models become more comprehensive, reliable, and accepted, there is a need to recognize and adopt principles of Good Modeling Practice (GMP) to ensure that multimedia models are applied with transparency and adherence to accepted scientific principles. We propose and discuss 6 principles of GMP for applying existing multimedia models in a decision-making context, namely 1) specification of the goals of the model assessment, 2) specification of the model used, 3) specification of the input data, 4) specification of the output data, 5) conduct of a sensitivity and possibly also uncertainty analysis, and finally 6) specification of the limitations and limits of applicability of the analysis. These principles are justified and discussed with a view to enhancing the transparency and quality of model-based assessments. PMID- 22318972 TI - What Contributes to the (Im)Balanced Division of Family Work Between the Sexes? AB - This study examines a comprehensive set of variables that have been proposed as explaining the imbalance of the division of family work between the sexes. The analyses use survey data of 735 dual-earner couples from Austria, the Netherlands, and Portugal. The results support theoretical explanations referring to time availability, gender ideology, relative resources, and the importance of characteristics of the family system. No support was obtained for the doing gender perspective. Additional findings suggest that increased consideration of psychological concepts adds to the understanding of why women do more family work than men. The analyses revealed similarities, but also differences between the factors that contribute to the division of household labor and childcare. PMID- 22318973 TI - Anti-idiotypic Fab Fragments Image a Conserved N-terminal Epitope Patch of Grass Pollen Allergen Phl p 1. AB - BACKGROUND AND AIMS: Naturally occurring anti-idiotypic antibodies structurally mimic the original antibody epitope. Anti-idiotypes, therefore, are interesting tools for the portrayal of conformational B-cell epitopes of allergens. In this study we used this strategy particularly for major timothy grass pollen (Phleum pratense) allergen Phl p 1. METHODS AND RESULTS: We used a combinatorial phage display library constructed from the peripheral IgG repertoire of a grass pollen allergic patient which was supposed to contain anti-idiotypic Fab specificities. Using purified anti-Phl p 1 IgG for biopanning, several Fab displaying phage clones could be isolated. 100 amplified colonies were screened for their binding capacity to anti-Phl p 1-specific antibodies, finally resulting in four distinct Fab clones according to sequence analysis. Interestingly, heavy chains of all clones derived from the same germ line sequence and showed high homology in their CDRs. Projecting their sequence information on the surface of the natural allergen Phl p 1 (PDB ID: 1N10) indicated matches on the N-terminal domain of the homo-dimeric allergen, including the bridging region between the two monomers. The resulting epitope patches were formed by spatially distant sections of the primary allergen sequence. CONCLUSION: In this study we report that anti idiotypic specificities towards anti-Phl p 1 IgG, selected from a Fab library of a grass pollen allergic patient, mimic a conformational epitope patch being distinct from a previously reported IgE epitope area. PMID- 22318974 TI - High-resolution single nucleotide polymorphism analysis distinguishes recrudescence and reinfection in recurrent invasive nontyphoidal Salmonella typhimurium disease. AB - BACKGROUND: Bloodstream infection with invasive nontyphoidal Salmonella (iNTS) is common and severe among human immunodeficiency virus (HIV)-infected adults throughout sub-Saharan Africa. The epidemiology of iNTS is poorly understood. Survivors frequently experience multiply recurrent iNTS disease, despite appropriate antimicrobial therapy, but recrudescence and reinfection have previously been difficult to distinguish. METHODS: We used high-resolution single nucleotide polymorphism (SNP) typing and whole-genome phylogenetics to investigate 47 iNTS isolates from 14 patients with multiple recurrences following an index presentation with iNTS disease in Blantyre, Malawi. We isolated nontyphoidal salmonellae organisms from blood (n = 35), bone marrow (n = 8), stool (n = 2), urine (n = 1), and throat (n = 1) samples; these isolates comprised serotypes Typhimurium (n = 43) and Enteritidis (n = 4). RESULTS: Recrudescence with identical or highly phylogenetically related isolates accounted for 78% of recurrences, and reinfection with phylogenetically distinct isolates accounted for 22% of recurrences. Both recrudescence and reinfection could occur in the same individual, and reinfection could either precede or follow recrudescence. The number of days to recurrence (23-486 d) was not different for recrudescence or reinfection. The number of days to recrudescence was unrelated to the number of SNPs accumulated by recrudescent organisms, suggesting that there was little genetic change during persistence in the host, despite exposure to multiple courses of antibiotics. Of Salmonella Typhimurium isolates, 42 of 43 were pathovar ST313. CONCLUSIONS: High-resolution whole-genome phylogenetics successfully discriminated recrudescent iNTS from reinfection, despite a high level of clonality within and among individuals, giving insights into pathogenesis and management. These methods also have adequate resolution to investigate the epidemiology and transmission of this important African pathogen. PMID- 22318975 TI - Characteristics and early outcomes of patients with Xpert MTB/RIF-negative pulmonary tuberculosis diagnosed during screening before antiretroviral therapy. AB - BACKGROUND: A proportion of patients with tuberculosis diagnosed by sputum culture during screening before antiretroviral therapy (ART) have false-negative Xpert MTB/RIF assay results (Xpert-negative tuberculosis). We determined the characteristics and early ART program outcomes of such patients. METHODS: Adult patients who enrolled in a South African township ART service were systematically screened for pulmonary tuberculosis regardless of symptoms by testing paired sputum samples with Xpert MTB/RIF and liquid culture. The ART service provided follow-up for all patients, and early (90-day) programmatic outcomes were determined. RESULTS: Among 602 patients screened, 523 had >=1 Xpert and culture result, yielding 89 culture-positive tuberculosis diagnoses. Of these, 37 (42%) of the patients with tuberculosis were Xpert-negative when a single sputum sample was tested, compared with 25 (28%) when 2 samples were tested. Compared with patients with Xpert-positive tuberculosis, those with Xpert-negative tuberculosis (using either definition) had substantially higher CD4 cell counts, lower plasma viral loads, higher hemoglobin concentrations, and higher body mass index. Their tuberculosis was also less advanced, with a lower frequency of prolonged cough (>=2 weeks), less extensive radiographic abnormalities, and a lower frequency of detectable lipoarabinomannan antigenuria and mycobacteriuria. Xpert-negative cases were all sputum smear negative with prolonged time to culture positivity (median, 21 days). Despite greater delays in starting tuberculosis treatment, Xpert-negative patients were less likely to die during follow-up. CONCLUSIONS: Compared to patients with Xpert-positive tuberculosis diagnosed during pre-ART screening, Xpert-negative cases had less advanced immunosuppression and less advanced tuberculosis and did not have adverse outcomes despite substantial delays in starting tuberculosis treatment. PMID- 22318976 TI - Neuroethics: A New Way of Doing Ethics. AB - The aim of this article is to argue, by example, for neuroethics as a new way of doing ethics. Rather than simply giving us a new subject matter-the ethical issues arising from neuroscience-to attend to, neuroethics offers us the opportunity to refine the tools we use. Ethicists often need to appeal to the intuitions provoked by consideration of cases to evaluate the permissibility of types of actions; data from the sciences of the mind give us reason to believe that some of these intuitions are less reliable than others. I focus on the doctrine of double effect to illustrate my case, arguing that experimental results suggest that appeal to it might be question-begging. The doctrine of double effect is supposed to show that there is a moral difference between effects that are brought about intentionally and those that are merely foreseen; I argue that the data suggest that we regard some effects as merely foreseen only because we regard bringing them about as permissible. Appeal to the doctrine of double effect therefore cannot establish that there are such moral differences. PMID- 22318977 TI - Bioactivity-guided fractionation of Phyllanthus orbicularis and identification of the principal anti HSV-2 compounds. AB - The antiherpes virus properties of Phyllanthus orbicularis Kunth, a Cuban-endemic medicinal plant, have been reported previously but data on its phytochemical profile and identification of antiviral metabolites as well as their mechanisms of action are still lacking. In this work, a bioactivity-guided phytochemical analysis was performed in order to isolate anti HSV-2 compounds. P. orbicularis contained mainly phenolic acids derivatives and flavonoids. The antiviral effects were attributed to (-)-epicatechin-3-O-gallate (EC(50) = 11.7 ug/mL), procyanidins B1 and B2 (EC(50) = 32.8 ug/mL and 24.2 ug/mL, respectively) as well as oligomeric and polymeric procyanidins and their gallate derivatives. The antiviral mechanisms of the active P. orbicularis extracts and fractions were also investigated and the inhibition of several HSV-2 early replication events and DNA synthesis were observed. This is the first study of extensive fractionation and phytochemical characterization of phenolic compounds from this species. PMID- 22318978 TI - Effects of block length in copolymers based on regioregular oligothiophenes linked with electron-accepting units. AB - Copolymers with an alternating structure of regioregular oligo(3-hexylthiophene) (O3HT) with different lengths and 2,5-dibutyl-3,6-di(thiophen-2-yl)pyrrolo[3,4 c]pyrrole-1,4(2H,5H)-dione (DPP) were synthesized through Stille coupling reaction. The light absorption of the copolymers can be rationally tuned to have a broad spectrum across the visible region by adjusting the length of O3HT. Organic solar cells fabricated with the copolymers and PCBM showed a broad photoresponse and a comparable efficiency to that of poly(3-hexylthiophene) (P3HT):PCBM cells. The external quantum efficiency and fluorescence spectra suggested that the intrachain energy transfer from the O3HT block to the vicinity of the DPP unit could limit the photovoltaic performance of the copolymers. PMID- 22318982 TI - Early diagnosis of hepatocellular carcinoma: it's not a matter of opinion. PMID- 22318983 TI - Integrin alpha4 impacts on differential adhesion of preadipocytes and stem cells on synthetic polymers. AB - Stem cells represent an ideal cell source for tissue engineering and regenerative medicine, because they can be readily isolated, expanded, differentiated and transplanted. For stem cell-based therapies, biomaterials are required to allow for a spatial distribution of the stem cells within a defined area in the body. In our recent studies, we analysed the interaction of a large panel of stem cell types with an array of biomaterials and demonstrated that a rational prediction of stem cell behaviour on a specific biomaterial is so far not possible. Interestingly, even ontogenetically related stem cell types, such as mesenchymal stem cells (MSCs), preadipocytes and dental pulp stem cells (DPSCs), exhibit distinct adhesion properties on the very same biomaterial surface. Therefore, we investigated integrin and extracellular matrix (ECM) protein expression of stem cells to relate gene expression to adhesion behaviour. MSCs, preadipocytes and DPSCs were cultured on selected synthetic polymers, such as Texin, a thermoplastic polyurethane, poly(dimethyl siloxane) (PDMS), poly-d,l-lactic acid (PDLLA) and l-lactic acid-trimehylene carbonate (Resomer(r) LT706). Integrins and ECM proteins were analysed by RT-PCR, real-time PCR and immunohistochemistry. Analysis of several adhesion molecules yielded that only one molecule, integrin alpha4, might play a significant role in differential adhesion on polymers for preadipocytes compared to DPSCs and MSCs. Thus, our studies on the molecular interactions of stem cells and polymers are expected to lead to a more profound understanding of the stem cell-biomaterial interactions to eventually allow for a rational biomaterial design. PMID- 22318984 TI - Oxidative annulation of beta-aminoporphyrins into pyrazine-fused diporphyrins. PMID- 22318985 TI - Congenital heart defects in a novel recurrent 22q11.2 deletion harboring the genes CRKL and MAPK1. AB - The proximal region of the long arm of chromosome 22 is rich in low copy repeats (LCR). Non-allelic homologous recombination (NAHR) between these substrates explains the high prevalence of recurrent rearrangements within this region. We have performed array comparative genomic hybridization in a normally developing girl with growth delay, microcephaly, and truncus arteriosus, and have identified a novel recurrent 22q11 deletion that spans LCR22-4 and partially affects the common 22q11.2 deletion syndrome and the distal 22q11 deletion syndrome. This deletion is atypical as it did not occur by NAHR between any of the major LCRs found on 22q11.2. However, the breakpoint containing regions coincide with highly homologous regions. An identical imbalance was reported previously in a patient with striking phenotypic similarity. Computational gene prioritization methods and biological evidence denote the genes CRKL and MAPK1 as the highest ranking candidates for causing congenital heart disease within the deleted region. PMID- 22318986 TI - P2X4 receptor channels form large noncytolytic pores in resting and activated microglia. AB - P2X4 ATP-gated cation channels have been shown to contribute to the microglial component of central sensitization, making their functional regulation a key element in chronic pain pathologies. Here we show that prolonged activation of native P2X4 receptor channels by ATP induces opening of a pore permeable to NMDG(+) and large fluorescent dyes in BV-2 microglial cells and primary murine microglia. This intrinsic pore formation mechanism is potentiated by LPS treatment, known to upregulate P2X4 expression in microglial cells and to mimic the microglial activation observed in neuropathic pain states. Sustained activation of the P2X7 channel subtype, also expressed in microglia, induces a pore formation that requires pannexin hemichannels and leads to plasma membrane blebbing and cytotoxicity. In contrast, P2X4 pore formation is unaffected by the pannexin blocker carbenoxolone, does not induce cytoskeletal rearrangements and does not lead to cell death. Furthermore, we show that P2X4 pore dilation is modulated by phosphoinositides (PIP(n) ) levels as it is inhibited by wortmannin, a blocker of PIP(n) synthesis, suggesting possible regulation by phospholipase C coupled pathways. Nonlethal P2X4 pore dilation could play a role in neuropathic pain by allowing the flux of large organic molecules in microglia. Different outcomes of P2X4 and P2X7 membrane permeabilization point to subtype-specific microglial responses to ATP in normal and pathological neuro-immune crosstalks. PMID- 22318990 TI - Ion-specific self-assembly of low-dimension aggregate structures of conjugated polymer at two-phase interface. AB - A novel and facile approach to manipulate the morphology of Cu(2+)-ion-specific assembly of conjugated polymer by coordinative interaction at an oil-water two phase interface is present. The application of increasing importance is the use of pi-conjugated polymers as receptors, exploiting their ability to selectively form complexes, which can obviously change the optical properties in solution and induce the formation of varied solid nano/microstructures. By this method, microtubes are formed through self-rolling of a strained ionic bilayer film at the oil/water interface. PMID- 22318991 TI - Major vault protein: a virus-induced host factor against viral replication through the induction of type-I interferon. AB - Major vault protein (MVP) is the major constituent of vaults and is involved in multidrug resistance, nucleocytoplasmic transport, and cell signaling. However, little is known about the role of MVP during viral infections. In this study, high levels of MVP were found in peripheral blood mononuclear cells, sera, and liver tissue from patients infected with hepatitis C virus (HCV) relative to healthy individuals. HCV infections resulted in elevated levels of MVP messenger RNA (mRNA) and protein expression in the hepatocyte cell lines Huh7.5.1 and Huh7. Further studies demonstrated that the nuclear factor kappa B (NF-kappaB) and Sp1 pathways are involved in the induction of MVP expression by HCV. Interestingly, MVP expression suppressed HCV replication and protein synthesis by way of induction of type-I interferon mRNA expression and protein secretion. Upon investigating the mechanisms behind this event, we found that MVP enhanced the expression of interferon regulatory factor 7 (IRF7), but not IRF3. Translocation of activated IRF7 and NF-kappaB from the cytosol to the nucleus was involved in this process. Furthermore, vesicular stomatitis virus, influenza A virus, and enterovirus 71 also induced MVP production, and MVP in turn hampered viral replication and production. CONCLUSION: MVP is a novel virus-induced host factor and its expression up-regulates type-I interferon production, leading to cellular antiviral responses. PMID- 22318992 TI - Differences in metabolomic profiles of male db/db and s/s, leptin receptor mutant mice. AB - Leptin, a protein hormone secreted by adipose tissue, plays an important role in regulating energy metabolism and the immune response. Despite similar extremes of adiposity, mutant mouse models, db/db, carrying spontaneous deletion of the active form of the leptin receptor (LEPR-B) intracellular signaling domain, and the s/s, carrying a specific point mutation leading to a dysfunctional LEPR-B STAT3 signaling pathway, have been shown to have robust differences in glucose homeostasis. This suggests specific effects of leptin, mediated by non-STAT3 LEPR B pathways. Differences in the LEPR-B signaling pathways in these two LEPR-B mutant mice models are expected to lead to differences in metabolism. In the current study, the hypothesized differences in metabolism were investigated using the metabolomics approach. Proton nuclear magnetic resonance spectroscopy ((1)HNMR) was conducted on 24 h urine samples in deuterium oxide using a 500 MHz instrument at 25 degrees C. Principle Component Analysis showed clear separation of urine NMR spectra between the groups (P < 0.05). The CHENOMX metabolite database was used to identify several metabolites that differed between the two mouse models. Significant differences (P < 0.05) in metabolites associated with the glycine, serine, and homocysteine metabolism were observed. The results demonstrate that the metabolomic profile of db/db and s/s mice are fundamentally different and provide insight into the unique metabolic effects of leptin exerted through non-STAT3 LEPR-B pathways. PMID- 22318993 TI - Activation of IKK/NF-kappaB provokes renal inflammatory responses in guanylyl cyclase/natriuretic peptide receptor-A gene-knockout mice. AB - The present study was aimed at determining the consequences of the disruption of guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) gene (Npr1) on proinflammatory responses of nuclear factor kappa B, inhibitory kappa B kinase, and inhibitory kappa B alpha (NF-kappaB, IKK, IkappaBalpha) in the kidneys of mutant mice. The results showed that the disruption of Npr1 enhanced the renal NF kappaB binding activity by 3.8-fold in 0-copy (-/-) mice compared with 2-copy (+/+) mice. In parallel, IKK activity and IkappaBalpha protein phosphorylation were increased by 8- and 11-fold, respectively, in the kidneys of 0-copy mice compared with wild-type mice. Interestingly, IkappaBalpha was reduced by 80% and the expression of proinflammatory cytokines and renal fibrosis were significantly enhanced in 0-copy mice than 2-copy mice. Treatment of 0-copy mice with NF-kappaB inhibitors andrographolide, pyrrolidine dithiocarbamate, and etanercept showed a substantial reduction in renal fibrosis, attenuation of proinflammatory cytokines gene expression, and significantly reduced IKK activity and IkBalpha phosphorylation. These findings indicate that the systemic disruption of Npr1 activates the renal NF-kappaB pathways in 0-copy mice, which transactivates the expression of various proinflammatory cytokines to initiate renal remodeling; however, inhibition of NF-kappaB pathway repairs the abnormal renal pathology in mutant mice. PMID- 22318994 TI - Human gene copy number spectra analysis in congenital heart malformations. AB - The clinical significance of copy number variants (CNVs) in congenital heart disease (CHD) continues to be a challenge. Although CNVs including genes can confer disease risk, relationships between gene dosage and phenotype are still being defined. Our goal was to perform a quantitative analysis of CNVs involving 100 well-defined CHD risk genes identified through previously published human association studies in subjects with anatomically defined cardiac malformations. A novel analytical approach permitting CNV gene frequency "spectra" to be computed over prespecified regions to determine phenotype-gene dosage relationships was employed. CNVs in subjects with CHD (n = 945), subphenotyped into 40 groups and verified in accordance with the European Paediatric Cardiac Code, were compared with two control groups, a disease-free cohort (n = 2,026) and a population with coronary artery disease (n = 880). Gains (>=200 kb) and losses (>=100 kb) were determined over 100 CHD risk genes and compared using a Barnard exact test. Six subphenotypes showed significant enrichment (P <= 0.05), including aortic stenosis (valvar), atrioventricular canal (partial), atrioventricular septal defect with tetralogy of Fallot, subaortic stenosis, tetralogy of Fallot, and truncus arteriosus. Furthermore, CNV gene frequency spectra were enriched (P <= 0.05) for losses at: FKBP6, ELN, GTF2IRD1, GATA4, CRKL, TBX1, ATRX, GPC3, BCOR, ZIC3, FLNA and MID1; and gains at: PRKAB2, FMO5, CHD1L, BCL9, ACP6, GJA5, HRAS, GATA6 and RUNX1. Of CHD subjects, 14% had causal chromosomal abnormalities, and 4.3% had likely causal (significantly enriched), large, rare CNVs. CNV frequency spectra combined with precision phenotyping may lead to increased molecular understanding of etiologic pathways. PMID- 22318996 TI - Effect of Salvia miltiorrhiza hydrophilic extract on the endothelial biomarkers in diabetic patients with chronic artery disease. AB - The aim of this pilot study was to investigate whether the administration of Salvia miltiorrhiza hydrophilic extract (SMHE) reduced the level of soluble vascular cell adhesion molecule-1 (sVCAM-1) and von Willebrand factor (vWF) in diabetic patients with coronary heart disease (CHD). Sixty-two diabetic patients with CHD were recruited and randomly assigned into placebo and treatment groups. Patients were given SMHE for 60 days. Levels of sVCAM-1, vWF and oxidative low density lipoprotein (oxLDL) were determined by using enzyme linked immunosorbent assay (ELISA). The results showed that the levels of VCAM-1 and vWF positively correlated with the level of oxLDL in diabetic patients with CHD. Levels of sVCAM 1 and vWF in serum were reduced significantly in patients receiving SMHE treatment at day 60 in comparison with the baseline. Administration of SMHE also led to a clear decrease in the levels of oxLDL in diabetic patients with CHD. In summary, this study suggests that SMHE has a potential protective effect on the development of diabetic cardiovascular disease. PMID- 22318995 TI - Interleukin-1beta modulates smooth muscle cell phenotype to a distinct inflammatory state relative to PDGF-DD via NF-kappaB-dependent mechanisms. AB - Smooth muscle cell (SMC) phenotypic modulation in atherosclerosis and in response to PDGF in vitro involves repression of differentiation marker genes and increases in SMC proliferation, migration, and matrix synthesis. However, SMCs within atherosclerotic plaques can also express a number of proinflammatory genes, and in cultured SMCs the inflammatory cytokine IL-1beta represses SMC marker gene expression and induces inflammatory gene expression. Studies herein tested the hypothesis that IL-1beta modulates SMC phenotype to a distinct inflammatory state relative to PDGF-DD. Genome-wide gene expression analysis of IL-1beta- or PDGF-DD-treated SMCs revealed that although both stimuli repressed SMC differentiation marker gene expression, IL-1beta distinctly induced expression of proinflammatory genes, while PDGF-DD primarily induced genes involved in cell proliferation. Promoters of inflammatory genes distinctly induced by IL-1beta exhibited over-representation of NF-kappaB binding sites, and NF-kappaB inhibition in SMCs reduced IL-1beta-induced upregulation of proinflammatory genes as well as repression of SMC differentiation marker genes. Interestingly, PDGF-DD-induced SMC marker gene repression was not NF-kappaB dependent. Finally, immunofluorescent staining of mouse atherosclerotic lesions revealed the presence of cells positive for the marker of an IL-1beta-stimulated inflammatory SMC, chemokine (C-C motif) ligand 20 (CCL20), but not the PDGF-DD induced gene, regulator of G protein signaling 17 (RGS17). Results demonstrate that IL-1beta- but not PDGF-DD-induced phenotypic modulation of SMC is characterized by NF-kappaB-dependent activation of proinflammatory genes, suggesting the existence of a distinct inflammatory SMC phenotype. In addition, studies provide evidence for the possible utility of CCL20 and RGS17 as markers of inflammatory and proliferative state SMCs within atherosclerotic plaques in vivo. PMID- 22318997 TI - When social networking is not working: individuals with low self-esteem recognize but do not reap the benefits of self-disclosure on Facebook. AB - The popular media have publicized the idea that social networking Web sites (e.g., Facebook) may enrich the interpersonal lives of people who struggle to make social connections. The opportunity that such sites provide for self disclosure-a necessary component in the development of intimacy--could be especially beneficial for people with low self-esteem, who are normally hesitant to self-disclose and who have difficulty maintaining satisfying relationships. We suspected that posting on Facebook would reduce the perceived riskiness of self disclosure, thus encouraging people with low self-esteem to express themselves more openly. In three studies, we examined whether such individuals see Facebook as a safe and appealing medium for self-disclosure, and whether their actual Facebook posts enabled them to reap social rewards. We found that although people with low self-esteem considered Facebook an appealing venue for self-disclosure, the low positivity and high negativity of their disclosures elicited undesirable responses from other people. PMID- 22318998 TI - Innovation relies on the obscure: a key to overcoming the classic problem of functional fixedness. AB - A recent analysis of real-world problems that led to historic inventions and insight problems that are used in psychology experiments suggests that during innovative problem solving, individuals discover at least one infrequently noticed or new (i.e., obscure) feature of the problem that can be used to reach a solution. This observation suggests that research uncovering aspects of the human semantic, perceptual, and motor systems that inhibit the noticing of obscure features would enable researchers to identify effective techniques to overcome those obstacles. As a critical step in this research program, this study showed that the generic-parts technique can help people unearth the types of obscure features that can be used to overcome functional fixedness, which is a classic inhibitor to problem solving. Subjects trained on this technique solved on average 67% more problems than a control group did. By devising techniques that facilitate the noticing of obscure features in order to overcome impediments to problem solving (e.g., design fixation), researchers can systematically create a tool kit of innovation-enhancing techniques. PMID- 22318999 TI - Omental grafting: a cell-based therapy for blood vessel repair. AB - Clinicians regularly transplant omental pedicles to repair a wide variety of injured tissues, but the basic mechanism underlying this efficacious procedure is not understood. One possibility that has not been addressed is the ability of omentum to directly contribute regenerative cells to injured tissues. We hypothesized that if omental progenitor cells could be mobilized to incorporate into damaged tissue, the power of this therapy would be greatly expanded. Labelled omental grafts were transplanted into a murine carotid artery injury model. Selected grafts were treated with thymosin beta4 (Tbeta4) prior to transplantation to investigate the effects of chemical potentiation on healing. We found treatment of grafts with Tbeta4-induced progenitor cells to fully integrate into the wall of injured vessels and differentiate into vascular smooth muscle. Myographic studies determined that arteries receiving Tbeta4-stimulated grafts were functionally indistinguishable from uninjured controls. Concurrent in vitro analyses showed that Tbeta4 promoted proliferation, migration and trans differentiation of cells via AKT signalling. This study is the first to demonstrate that omentum can provide progenitor cells for repair, thus revealing a novel and naturally occurring source of vascular smooth muscle for use in cell based therapies. Furthermore, our data show that this system can be optimized with inducing factors, highlighting a more powerful therapeutic potential than that of its current clinical application. This is a paradigm-setting concept that lays the foundation for the use of chemical genetics to enhance therapeutic outcomes in a myriad of fields. PMID- 22319000 TI - Insights into the mechanistic pathway of the Pantoea agglomerans phenylalanine aminomutase. PMID- 22319001 TI - Teratogenicity of mycophenolate confirmed in a prospective study of the European Network of Teratology Information Services. AB - After maternal exposure to mycophenolate in pregnancy a high number of fetal losses and a specific pattern of birth defects consisting of microtia, cleft lip, and other anomalies have been reported. However, so far, prospective data on pregnancy outcome allowing quantitative risk assessment are missing. We report on 57 prospectively ascertained pregnancies after maternal therapy with mycophenolate (mycophenolate mofetil or mycophenolate sodium) identified by European Teratology Information Services (ETIS) through their risk consultation process. The outcome of these prospective pregnancies was as follows: 16 spontaneous abortions, 12 elective terminations of pregnancy (ETOP) (including two late terminations for multiple malformations consistent with mycophenolate embryopathy), and 29 liveborn infants. The probability of spontaneous abortion was about 45% (95% CI 29 to 66%) estimated using survival analysis technique. Six out of 29 live born infants had major congenital defects: Two with external auditory canal atresia (EACA) (with and without microtia), one with tracheo esophageal atresia, one with severe hydronephrosis, one with an atrial septal defect (ASD) and one with a myelomeningocele. Thus, at least four fetuses/infants of our prospective case series had a clinical phenotype consistent with mycophenolate embryopathy. Our results confirm a high incidence of major malformations (26%) after first trimester exposure to mycophenolate. Apart from exposure to mycophenololate, the underlying maternal disease and concomitant medication may also have contributed to the other poor pregnancy outcomes such as a high rate of spontaneous abortions, prematurity (62%), and low birth weight (31%). PMID- 22319002 TI - Medullary thyroid carcinoma and 2q37 deletion in a patient with nevoid basal cell carcinoma syndrome: clinical description and genetic analysis. AB - BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS) is a rare, inheritable, multisystem disorder characterized by numerous basal cell carcinomas (BCCs), maxillary keratocyst, and musculoskeletal malformations. Occasionally, it is associated with malignancies like rhabdomyoma, melanoma, and sinonasal undifferentiated carcinoma, to name a few. METHODS: A patient presented with NBCCS with a medullary thyroid carcinoma. Clinical, surgical details, and germline genetic analysis are herein described. RESULTS: A 32-year-old woman was referred to our department with suspicion of medullary thyroid carcinoma, which was confirmed by histopathological examination. The patient was diagnosed as also having NBCCS. Germline mutation analysis indicated wild-type genes PTCH1 and RET. DNA copy number analysis by high resolution microarray comparative genomic hybridization (CGH) revealed a small interstitial loss at chromosomal band 2q37.3. CONCLUSION: To our knowledge, this is the first described patient with NBCCS carrying a medullary thyroid carcinoma and a 2q37 deletion, which confirms that this syndrome can be associated with many different malignancies. PMID- 22319003 TI - Regulation of CCL20 expression in astrocytes by IL-6 and IL-17. AB - Astrocytes have an important role in the regulation of inflammation within the central nervous system (CNS). In neuroinflammatory conditions such as multiple sclerosis, numerous cytokines and chemokines are elevated including IL-6, IL-17, and CCL20. IL-17 enhances IL-6 signaling and subsequent IL-6 expression in astrocytes. CCL20 is a CC motif chemokine that functions as a chemoattractant to facilitate the recruitment of CCR6-expressing cells, including Th17 cells. In this study, we examined the role of IL-6 and IL-17 on CCL20 production in primary murine astrocytes. IL-6 in combination with the IL-6 soluble receptor (sIL-6R) stimulated CCL20 expression in part through STAT3 activation, whereas IL-17 alone had no effect. However, the combination of IL-6, sIL-6R, and IL-17 led to a robust increase in CCL20 production. IL-17 increased the activation-associated phosphorylation of NF-kappaB, and inhibition of the NF-kappaB pathway significantly inhibited the enhancement of CCL20 expression by IL-17. In addition, chromatin immunoprecipitation revealed that stimulation of primary astrocytes with IL-6 plus the sIL-6R induced STAT3 binding to the CCL20 promoter. Combined stimulation with IL-6, sIL-6R, and IL-17 increased the recruitment of phosphorylated NF-kappaB to the CCL20 promoter, increased binding of coactivators such as p300 and CBP, and enhanced H3 and H4 histone acetylation, consistent with a transcriptionally active gene. The astrocyte-produced CCL20 increased T cell migration as determined by transwell migration assay. Collectively, these results suggest that astrocytes, in response to IL-6, sIL-6R, and IL-17, may shift chemokine production to that favoring T cell recruitment to the CNS. PMID- 22319004 TI - Reliable identification of "truly low" thromboembolic risk in patients initially diagnosed with "lone" atrial fibrillation: the Belgrade atrial fibrillation study. AB - BACKGROUND: The CHA(2)DS(2)-VASc (Congestive heart failure, Hypertension, Age >=75 years, Diabetes mellitus, previous Stroke/transient ischemic attack [TIA], Vascular disease, Age 65-74 years, and Sex category [female gender]) schema recently has been introduced to complement the CHADS(2) (Congestive heart failure, Hypertension, Age >75 years, Diabetes mellitus, and previous stroke or TIA) score and improve the identification of atrial fibrillation (AF) patients at "truly low risk" for thromboembolism. We tested the predictive ability of the CHA(2)DS(2)-VASc, CHADS(2), and van Walraven risk stratification schemes in a cohort of "lone" AF patients with a 12-year follow-up. METHODS AND RESULTS: We conducted a registry-based, observational cohort study of 345 patients initially diagnosed with "lone" AF between 1992 and 2007. At baseline, all patients had the CHADS(2) and van Walraven scores of 0, and 262 (75.9%) had a CHA(2)DS(2)-VASc score of 0. During follow-up (or within a year prior to stroke), 228 (66.1%), 234 (67.8%), and 150 patients (43.5%) retained the CHADS(2), van Walraven, and CHA(2)DS(2)-VASc scores of 0, respectively. The overall rate of ischemic stroke was 0.19 (95% CI: 0.18-0.20) per 100 patient years. In the multivariable analysis, only the CHA(2)DS(2)-VASc score of 0 was significantly related to the absence of stroke (odds ratio 5.1, 95% CI: 1.5-16.8, P=0.008). Only the CHA(2)DS(2)-VASc score had a significant prediction ability (c-statistic 0.72 [0.61-0.84], P=0.031). CONCLUSIONS: The CHA(2)DS(2)-VASc score reliably identified the "lone" AF patients who were at "truly low risk" for thromboembolism, and was the only tested risk stratification scheme with a significant predictive ability for thromboembolism among lone AF patients. PMID- 22319005 TI - Relation of the HAS-BLED bleeding risk score to major bleeding, cardiovascular events, and mortality in anticoagulated patients with atrial fibrillation. AB - BACKGROUND: Stroke risk in atrial fibrillation (AF) using oral vitamin K antagonists is closely related to bleeding risk. The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR [international normalized ratio], elderly, drugs/alcohol concomitantly) bleeding score has demonstrated usefulness in assessing major bleeding risk in patients with AF. However, risk factors for warfarin-associated bleeding also predict stroke risk in patients with AF. We tested the usefulness of the HAS-BLED score for predicting both major bleeding and cardiovascular events in a cohort of anticoagulated patients with AF. METHODS AND RESULTS: We recruited 965 consecutive anticoagulated outpatients with permanent or paroxysmal AF who were stabilized for at least 6 months on oral anticoagulation (international normalized ratio, 2.0-3.0). Medical history and HAS-BLED score were assessed. Cox regression models were used to determine the association between clinical risk factors and bleeding episodes, adverse cardiovascular events, and mortality. The median HAS-BLED score was 2 (range, 0-6; 29% with a score >=3 [ie, high risk]). Median follow-up was 861 days (range, 718-1016 days). Independent predictors for major bleeding were age >=75 years (hazard ratio [HR], 1.74; 95% CI, 1.05-2.87; P=0.030), male sex (HR, 1.70; 95% CI, 1.03-2.80; P=0.036), renal impairment (HR, 2.12; 95% CI, 1.20-3.73; P=0.010), previous bleeding episode (HR, 6.00; 95% CI, 3.73-9.67; P<0.001), current alcohol consumption (HR, 2.28; 95% CI, 1.03-5.06; P=0.043), and concomitant malignant disease (HR, 2.17; 95% CI, 1.13-4.18; P=0.020). Independent predictors for adverse cardiovascular events were age >75 years (HR, 2.20; 95% CI, 1.40-3.46; P=0.001), heart failure (HR, 1.78; 95% CI, 1.20-2.86; P=0.001), and previous stroke (HR, 1.85; 95% CI, 1.20-2.86; P<0.001). The HAS-BLED score was highly predictive for major bleeding events (HR, 2.04; 95% CI, 1.68-2.49; P<0.001) and adverse cardiovascular events (HR, 1.51; 95% CI, 1.27 1.81; P<0.001). The incidence of both bleeding and adverse cardiovascular events was higher as HAS-BLED score increased, and crude bleeding rates only exceeded thrombotic events at a HAS-BLED score >3. The HAS-BLED score also predicted all cause mortality (HR, 1.68; 95% CI, 1.40-2.01; P<0.001). CONCLUSIONS: The HAS-BLED score not only is useful in the assessment of bleeding risk, but also shows some predictive value for cardiovascular events and mortality in anticoagulated patients with AF, consistent with the relationship between thrombosis and bleeding. Nonetheless, the HAS-BLED score has been designed for predicting bleeding risk rather than thrombotic events per se, and specific risk scores for cardiovascular events and mortality should be applied for these events. PMID- 22319006 TI - In vitro inhibition of CYP3A4 by the multiherbal commercial product Sambucus Force and its main constituents Echinacea purpurea and Sambucus nigra. AB - The multiherbal product Sambucus Force contains Echinacea purpurea and Sambucus nigra as its main constituents. The aims of this study were to evaluate Sambucus Force's inhibition potential and inhibition mechanisms towards CYP3A4, and to evaluate the inhibitory co-contribution of E. purpurea and S. nigra. Metabolic studies were performed with recombinant human CYP3A4, with testosterone as substrate. Sambucus Force inhibited CYP3A4 activity with a mean (95% confidence interval) half maximal inhibitory concentration (IC(50) ) value of 1192 (1091 1302) ug/mL. The inhibitory potency seems exclusively to be exerted by E. purpurea, implicating an insignificant inhibition by S. nigra. The inhibition by E. purpurea as a single herb was in agreement with mechanism-based inhibition with heterotropic positive cooperative effects. Echinacea purpurea acted differently in the multiherbal product, which showed a dual inhibition profile with both an uncompetitive (substrate-dependent) inhibition and a time-dependent (substrate-independent) inhibitory mechanism. These mechanistic differences are suggested to be caused by herb-herb interactions in the multiherbal product. The CYP3A4 inhibition of Sambucus Force in vitro is considered relatively weak, but recommended high herbal dosages might enhance the potential for clinical interactions. PMID- 22319007 TI - Control of the timing and dosage of IGF-I delivery from encapsulated cells. AB - We report here on the development and characterization of a cell-based system for the regulated delivery of bioactive insulin-like growth factor I (IGF-I). A stable mammalian cell line, CHO-K1 Tet-IGFI, was genetically modified to have tetracycline-induced transcription of the human IGF-I gene. Cells were activated to express IGF-I in the presence of doxycycline (DOX), a tetracycline derivative, while expression was inactivated in the absence of DOX. Temporal, or on-off, release of IGF-I from cells encapsulated within Ca2+-alginate hydrogels was demonstrated in a pilot study over the course of 10 days in culture. Released growth factor was bioactive, exhibiting a proliferative effect comparable to recombinant purified IGF-I protein. The dosage levels and temporal control of IGF I release from encapsulated cells meet the requirements of orthopedic wound repair, making this approach an attractive means for the controlled synthesis and delivery of growth factors in situ for wound healing. PMID- 22319008 TI - Small-molecule inhibitors of NMO-IgG binding to aquaporin-4 reduce astrocyte cytotoxicity in neuromyelitis optica. AB - Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of spinal cord and optic nerve caused by pathogenic autoantibodies (NMO-IgG) against astrocyte aquaporin-4 (AQP4). We developed a high-throughput screen to identify blockers of NMO-IgG binding to human AQP4 using a human recombinant monoclonal NMO-IgG and transfected Fisher rat thyroid cells stably expressing human M23 AQP4. Screening of ~60,000 compounds yielded the antiviral arbidol, the flavonoid tamarixetin, and several plant-derived berbamine alkaloids, each of which blocked NMO-IgG binding to AQP4 without affecting AQP4 expression, array assembly, or water permeability. The compounds inhibited NMO-IgG binding to AQP4 in NMO patient sera and blocked NMO-IgG-dependent complement- and cell-mediated cytotoxicity with IC(50) down to ~5 MUM. Docking computations identified putative sites of blocker binding at the extracellular surface of AQP4. The blockers did not affect complement-dependent cytotoxicity caused by anti-GD3 antibody binding to ganglioside GD3. The blockers reduced by >80% the severity of NMO lesions in an ex vivo spinal cord slice culture model of NMO and in mice in vivo. Our results provide proof of concept for a small-molecule blocker strategy to reduce NMO pathology. Small-molecule blockers may also be useful for other autoimmune diseases caused by binding of pathogenic autoantibodies to defined targets. PMID- 22319009 TI - Ablation of Pparg2 impairs lipolysis and reveals murine strain differences in lipolytic responses. AB - We investigate the role of PPARg2 as a regulator of lipolysis and its interaction with specific genetic backgrounds as determinants of the severity of the metabolic phenotype. This question was prompted by our previous characterization of Pparg2-knockout (KO) mice that revealed striking genetic background differences in the severity of their adipose tissue development impairment and dysfunction. Analysis is done of pharmacological lipolytic responses combined with protein and mRNA expression analysis in isolated adipocytes from the gonadal pad of Pparg2-KO mice in 2 different backgrounds (129S6/SvEv and C57BL/6). We provide evidence of the prolipolytic role of PPARg2 and how these effects are modulated by genetic background, leading to differential severity of metabolic syndrome. Specifically, ablation of Pparg2 reduced both basal and stimulated lipolysis as a result of impaired beta(3)-AR signaling, a general defect at downstream lipases, and increased insulin-mediated antilipolytic action. Of note, the C57BL/6 Pparg2-KO mice exhibited more active lipolytic response to catecholamines than 129S6/SvEv Pparg2-KO mice with respect to their wild-type controls. Pparg2-KO mice exhibit metabolic inflexibility resulting from the combined effects of impaired lipid deposition coupled with impaired lipolytic lipid mobilization. The genetic background-dependent differences in lipolysis may account for Pparg2-KO background-specific differences in the severity of their metabolic disturbances. Our findings identify the isoform Pparg2 as an integrator of the adipose lipid metabolism coordinating both anabolic and catabolic processes. PMID- 22319010 TI - Dynamics of the subcellular localization of RalBP1/RLIP through the cell cycle: the role of targeting signals and of protein-protein interactions. AB - The small G protein Ras regulates many cell processes, such as gene expression, proliferation, apoptosis, and cell differentiation. Its mutations are associated with one-third of all cancers. Ras functions are mediated, at least in part, by Ral proteins and their downstream effector the Ral-binding protein 1 (RalBP1). RalBP1 is involved in endocytosis and in regulating the dynamics of the actin cytoskeleton. It also regulates early development since it is required for the completion of gastrulation in Xenopus laevis. RalBP1 has also been reported to be the main transporter of glutathione electrophiles, and it is involved in multidrug resistance. Such a variety of functions could be explained by a differential regulation of RalBP1 localization. In this study, we have detected endogenous RalBP1 in the nucleus of interphasic cells. This nuclear targeting is mediated by nuclear localization sequences that map to the N-terminal third of the protein. Moreover, in X. laevis embryos, a C-terminal coiled-coil sequence mediates RalBP1 retention in the nucleus. We have also observed RalBP1 at the level of the actin cytoskeleton, a localization that depends on interaction of the protein with active Ral. During mitosis RalBP1 also associates with the mitotic spindle and the centrosome, a localization that could be negatively regulated by active Ral. Finally, we demonstrate the presence of post transcriptional and post-translational isoforms of RalBP1 lacking the Ral-binding domain, which opens new possibilities for the existence of Ral-independent functions. PMID- 22319011 TI - Dye molecules for simple co-sensitization process: fabrication of mixed-dye sensitized solar cells. PMID- 22319012 TI - Contribution to the lichen biota of Slovenia XII. Some lichens from Logarska dolina. AB - A list of 94 species is presented including Bacidia subacerina and Lopadium disciforme as new for Slovenia and Bilimbia accedens, Lecanora leptyrodes, Megalaria grossa, Mycobilimbia epixanthoides, Rinodina efflorescens, and Sclerophora peronella as new for the alpine phytogeographical region of Slovenia. PMID- 22319013 TI - Voice outcomes after concurrent chemoradiotherapy for advanced nonlaryngeal head and neck cancer: a prospective study. AB - BACKGROUND: The voice impact of treatment for nonlaryngeal head and neck primary sites remains unknown. METHODS: We conducted a prospective study of a consecutive sample of patients undergoing chemoradiation for nonlaryngeal head and neck cancer. The Voice Symptom Scale (VoiSS) was completed, and voice recordings were made at 3 time-points. RESULTS: Of 42 recruited patients, 34 completed the measures before and in the early posttreatment phase (mean 16.5 weeks), while 21 patients were assessed at the final time-point (mean, 20.4 months). VoiSS scores showed statistically significant progressive deterioration in the total score (p = .02) and impairment subscale (p < .0001) through to the final assessment. Acoustic measures and perceptual ratings deteriorated significantly (p < .001) in the early posttreatment weeks and improved at the final assessment, but not to the baseline. Interrater agreement was excellent for expert measures. CONCLUSION: To the best of our knowledge, this is the first prospective study to show that chemoradiation therapy for nonlaryngeal head and neck cancer has a significant effect on the patients' self-reported voice quality, even in the long term. PMID- 22319014 TI - Raman spectroscopy and CARS microscopy of stem cells and their derivatives. AB - The characterisation of stem cells is of vital importance to regenerative medicine. Failure to separate out all stem cells from differentiated cells before therapies can result in teratomas - tumours of multiple cell types. Typically, characterisation is performed in a destructive manner with fluorescent assays. A truly non-invasive method of characterisation would be a major breakthrough in stem cell-based therapies. Raman spectroscopy has revealed that DNA and RNA levels drop when a stem cell differentiates into other cell types, which we link to a change in the relative sizes of the nucleus and cytoplasm. We also used Raman spectroscopy to investigate the biochemistry within an early embryo, or blastocyst, which differs greatly from colonies of embryonic stem cells. Certain cell types that differentiate from stem cells can be identified by directly imaging the biochemistry with CARS microscopy; examples presented are hydroxyapatite - a precursor to bone, and lipids in adipocytes. PMID- 22319015 TI - The magnitude of the antigen-specific T cell response is separated from the severity of spinal cord histopathology in remitting-relapsing experimental autoimmune encephalomyelitis. AB - Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system. The remitting-relapsing experimental autoimmune encephalomyelitis (EAE) in the SJL mouse strain is a common animal model for MS and similar to the human disease it is considered to be T helper cell mediated. Besides interferon-gamma secreting T(H)1 cells in particular the T(H)17 subset is believed to be highly pathogenic. Spreading of the T(H)1 and T(H)17 response to newly emerging determinants has been used to explain clinical disease relapse, but if the magnitude of the T(H)1/T(H)17 response is linked to clinical relapse severity has remained unresolved. Here, we assessed clinical EAE severity, the extent of spinal cord histopathology and the magnitude of the antigen-specific T helper cell and autoantibody response in proteolipid protein peptide 139-151 (PLP:139-151) immunized SJL mice in clinical remission and relapse. We demonstrate that spinal cord histopathology comprised inflammation, demyelination as well as axonal loss and correlated well with clinical disease severity. Although the degree of spinal cord histopathology and clinical severity was separated from the PLP:139-151 specific T(H)1/T(H)17 cell and antibody response, it was linked to the number of infiltrating macrophages and activated microglia. In particular, there was a correlation between their secretion product interleukin-1beta and the degree of axonal loss. Although CD4(+) T cells seem to be mainly involved in disease initiation, we suggest that it is the downstream activation of the innate immune response that defines the magnitude of the disease outcome. PMID- 22319016 TI - OMIP-006: phenotypic subset analysis of human T regulatory cells via polychromatic flow cytometry. AB - This panel was optimized for the enumeration and phenotypic characterization of T regulatory cells (Tregs) within the CD4+ T-cell pool using human peripheral blood mononuclear cells (PBMC) using intranuclear and intracellular staining methods. The panel was optimized for HIV+ clinical trial specimens through the use of HIV infected and normal donor PBMC. Because the panel is to be used in the context of testing cryopreserved PBMC obtained from multiple sites participating in clinical trials, it was essential to develop an assay that performed well using cryopreserved PBMC. Other tissue types have not been tested. PMID- 22319017 TI - Platinum-catalyzed hydrosilylations of internal alkynes: harnessing substituent effects to achieve high regioselectivity. PMID- 22319018 TI - Are mould hepatotoxins responsible for kava hepatotoxicity? AB - Previous studies with kava components such as kavalactones, pipermethystine and flavokavain B have demonstrated hepatotoxicity from these constituents. Regardless, there has recently been speculation that adulterants or impurities such as the mould hepatotoxin aflatoxin are a more likely cause of kava hepatotoxicity, despite a paucity of supporting evidence. Although there is limited similarity between acute kava hepatotoxicity and acute aflatoxicosis, and background levels of aflatoxin have been detected in kava samples, unless epidemiological investigations can uncover direct evidence implicating mould hepatotoxins, it remains more likely that chemical constituents of kava are the cause of the hepatotoxicity from kava. PMID- 22319019 TI - Second primary lung cancer after head and neck squamous cell cancer: population based study of risk factors. AB - BACKGROUND: Patients with head and neck squamous cell cancer (HNSCC) are at risk of developing second primary lung cancer (SPLC). METHODS: Among 61,883 patients with HNSCC from the Surveillance, Epidemiology and End Results (SEER) database, 4522 developed SPLC (any histology) >=2 months after HNSCC. We correlated risk with demographic and tumor-related parameters. RESULTS: The risk of SPLC after HNSCC was 5.8%, 11.4%, and 16.4% at 5, 10, and 15 years, respectively. From Cox regression, significantly adverse (p < .0001) risk factors for SPLC included: regional versus localized HNSCC stage (hazard ratio [HR] = 1.16), hypopharyngeal or supraglottic laryngeal site (HR = 1.57), increased age (HR = 1.26/decade), black race (HR = 1.27), and male sex (HR = 1.26). Glottic (HR = 0.75) and tonsillar or oral cavity sites (HR = 0.80) were associated with significantly (p < .0001) lower risks of SPLC. CONCLUSION: From population-based actuarial analyses, HNSCCs with more aggressive clinicopathologic features were more apt to develop SPLC, suggestive of similar environmental and/or host factors for these cancers. PMID- 22319020 TI - A genome-wide association study for coronary artery disease identifies a novel susceptibility locus in the major histocompatibility complex. AB - BACKGROUND: Recent genome-wide association studies (GWAS) have identified several novel loci that reproducibly associate with coronary artery disease (CAD) and/or myocardial infarction risk. However, known common CAD risk variants explain only 10% of the predicted genetic heritability of the disease, suggesting that important genetic signals remain to be discovered. METHODS AND RESULTS: We performed a discovery meta-analysis of 5 GWAS involving 13 949 subjects (7123 cases, 6826 control subjects) imputed at approximately 5 million single nucleotide polymorphisms, using pilot 1000 Genomes-based haplotypes. Promising loci were followed up in an additional 5 studies with 11 032 subjects (5211 cases, 5821 control subjects). A novel CAD locus on chromosome 6p21.3 in the major histocompatibility complex (MHC) between HCG27 and HLA-C was identified and achieved genome-wide significance in the combined analysis (rs3869109; p(discovery)=3.3*10(-7), p(replication)=5.3*10(-4)p(combined)=1.12*10(-9)). A subanalysis combining discovery GWAS showed an attenuation of significance when stringent corrections for European population structure were used (P=4.1*10(-10) versus 3.2*10(-7)), suggesting that the observed signal is partly confounded due to population stratification. This gene dense region plays an important role in inflammation, immunity, and self-cell recognition. To determine whether the underlying association was driven by MHC class I alleles, we statistically imputed common HLA alleles into the discovery subjects; however, no single common HLA type contributed significantly or fully explained the observed association. CONCLUSIONS: We have identified a novel locus in the MHC associated with CAD. MHC genes regulate inflammation and T-cell responses that contribute importantly to the initiation and propagation of atherosclerosis. Further laboratory studies will be required to understand the biological basis of this association and identify the causative allele(s). PMID- 22319021 TI - Cytotoxic functions and susceptibility to apoptosis of human CD56(bright) NK cells differentiated in vitro from CD34+ hematopoietic progenitors. AB - Cytotoxic functions and susceptibility to apoptosis are crucial aspects of NK cells suitable to counter cancer after infusion in oncologic patients. To test the feasibility and the usefulness of infusing in vitro generated NK cells, these two features were investigated in NK cells developed in vitro from CD34+ hematopoietic progenitors. Purified CD34+ cells were cultured for 15-30 days with FLT-3 ligand (FLT3-L) and IL-15 with or without IL-21. To induce terminal differentiation, NK cells were cultured for further 15 days with IL-15, IL-21, or their combination. A CD56(dim) /CD16+ NK subset, expressing high level of perforin, granzymes, and LFA-1, appeared early in cultures with FLT3-L, IL-15, and IL-21, but it quickly died, indicating its predisposition to apoptosis. On the contrary, CD56(bright) NK cells generated after 30 days of culture with FLT3 L plus IL-15 did not show a considerable apoptosis, nevertheless only a subset of these cells expressed granzyme-B, perforin, LFA-1, and CD94-CD159a heterodimer, indicating a functional immaturity. Interestingly, further 15 days of culture with IL-21 plus IL-15 did not induce the generation of CD56(dim) cells from the CD56(bright) subset and actually inhibited IL-15-induced maturation/activation of this latter subset. In fact, IL-15 alone upregulated granzyme-B, TRAIL, Fas ligand, CD94-CD159a, LFA-1, CD16, KIRs, and TRAIL-R2 on CD56(bright) NK cells. Our results suggest that during differentiation CD56(bright) NK cells, similarly to mature activated NK cells, become highly cytotoxic and are relatively resistant to apoptosis induced by TNF family members. PMID- 22319022 TI - From esters to alcohols and back with ruthenium and osmium catalysts. AB - There and back again: hydrogenation of esters and the reverse reaction of dehydrogenative coupling of alcohols are efficiently catalyzed by dimeric complexes of Ru and Os under neutral conditions. The Os dimer is an outstanding catalyst for the hydrogenation of alkenoates and triglycerides, and allows production of fatty alcohols from olive oil. This complex converts ethanol into ethyl acetate and hydrogen under reflux. PMID- 22319023 TI - Ecological roles of the parasitic phytomyxids (plasmodiophorids) in marine ecosystems - a review. AB - Phytomyxea (plasmodiophorids) is an enigmatic group of obligate biotrophic parasites. Most of the known 41 species are associated with terrestrial and freshwater ecosystems. However, the potential of phytomyxean species to influence marine ecosystems either directly by causing diseases of their hosts or indirectly as vectors of viruses is enormous, although still unexplored. In all, 20% of the currently described phytomyxean species are parasites of some of the key primary producers in the ocean, such as seagrasses, brown algae and diatoms; however, information on their distribution, abundance and biodiversity is either incomplete or lacking. Phytomyxean species influence fitness by altering the metabolism and/or the reproductive success of their hosts. The resulting changes can (1) have an impact on the biodiversity within host populations, and (2) influence microbial food webs because of altered availability of nutrients (e.g. changed metabolic status of host, transfer of organic matter). Also, phytomyxean species may affect their host populations indirectly by transmitting viruses. The majority of the currently known single-stranded RNA marine viruses structurally resemble the viruses transmitted by phytomyxean species to crops in agricultural environments. Here, we explore possible ecological roles of these parasites in marine habitats; however, only the inclusion of Phytomyxea in marine biodiversity studies will allow estimation of the true impact of these species on global primary production in the oceans. PMID- 22319024 TI - Fish liver and seagull eggs, vitamin D-rich foods with a shadow: results from the Norwegian Fish and Game Study. AB - SCOPE: Fish liver, fish liver oil, oily fish and seagull eggs have been major sources of vitamin D for the coastal population of Norway. They also provide dioxin and polychlorinated dioxin-like compounds (dl-compounds), which may interfere with vitamin D homeostasis. We investigated whether serum 25 hydroxyvitamin D (25(OH)D) might be compromised by concomitant intake of dl compounds. METHODS AND RESULTS: We studied 182 adults participating in the Norwegian Fish and Game Study. Participants who consumed fish liver and/or seagull eggs had higher dl-compound intake and blood concentrations than non consumers (p < 0.001). Vitamin D intake was higher (p < 0.001), whereas serum 25(OH)D was lower (p = 0.029) in consumers than in non-consumers. Among non consumers, vitamin D intake was associated with serum 25(OH)D (beta=1.06; 95% CI: 0.48, 1.63). This association was weaker among consumers (beta = 0.52; 95% CI: 0.05, 1.08), but strengthened when adjusted for retinol intake (beta = 0.66; 95% CI: 0.12, 1.21). The association between vitamin D intake and serum 25(OH)D did not seem to be compromised by intake of dl-compounds. CONCLUSION: To secure adequate vitamin D status while keeping the intake of dioxins and dl polychlorinated biphenyls low, a healthy diet should include both supplemental vitamin D and oily fish. Despite high nutrient content, dietary fish liver and seagull eggs should be restricted, due to dl-compounds and possible vitamin A-D antagonism. PMID- 22319025 TI - Sexual perceptions and practices of young people in Northern Thailand. AB - This study draws together survey and qualitative data on sexual practices among more than 1,750 young Northern Thai people aged 17-20 years. The survey data indicate that sexually active young people frequently engage in, or are subjected to, risk-taking behaviours that may expose them to sexually transmitted infections and unwanted pregnancies. These include having multiple sexual partners and quite frequent partner turnover. High percentages also engage in unprotected sexual intercourse with various types of sexual partner (steady, casual and paid), and young women especially had often experienced sexual coercion. Qualitative data revealed a mixture of perceptions and practices affecting sexual intercourse among the young, such as having unplanned sex, engaging in sexual relations to display love or cement committed relationships, and having serial relationships, both monogamous and non-monogamous. We conclude that condom use should be a central focus of activities aimed at preventing adverse sexual health outcomes, but that new intervention approaches to encourage use of other contraceptives are also needed. Changes in sexual norms among young people also need to be acknowledged and accepted by older Thai generations in order for programs and interventions to combat negative sexual and reproductive health consequences to be more effective. PMID- 22319026 TI - Development and validation of Hong Kong Rapid Estimate of Adult Literacy in Dentistry. AB - AIM: To develop and validate an instrument, the Hong Kong Rapid Estimate of Adult Literacy in Dentistry (HKREALD-30). METHODS: The Rapid Estimate of Adult Literacy in Dentistry (REALD-99) was translated into Chinese and modified in the pretest. A total of 200 parents of pediatric dental patients were interviewed using this modified scale and administered additional three sets of self-reported questionnaires. The 99 items of the scale were reduced to 30 (HKREALD-30). Concurrent validity was tested by comparing the HKREALD-30 scores with the participants' educational level, pattern of dental visits and reading habits. Convergent validity was tested by examining the association between HKREALD-30 and the Test of Functional Health Literacy in Dentistry (TOFHLiD). The test retest reliability and internal consistency of HKREALD-30 were also evaluated. RESULTS: A significant correlation (P < 0.01) was found between HKREALD-30 and participants' reading habits. HKREALD-30 was also highly correlated with TOFHLiD (Spearman's rho = 0.693, P < 0.01). In the regression model, HKREALD-30 was positively associated with TOFHLiD (P < 0.05) after controlling for participants' characteristics. The intra-class correlation coefficient of HKREALD-30 was 0.78 and the Cronbach's alpha was 0.84. CONCLUSION: Initial testing of HKREALD-30 suggested that it is a valid and reliable instrument for the basic screening of oral health literacy among Chinese people in Hong Kong. PMID- 22319027 TI - An approach to the site-selective deoxygenation of hydroxy groups based on catalytic phosphoramidite transfer. PMID- 22319028 TI - Pattern of adrenal hormonal secretion in patients with adrenal adenomas: the relevance of aldosterone in arterial hypertension. AB - CONTEXT: Approximately 10% of hypertensives are considered to exhibit autonomous aldosterone secretion (AAS). Although adrenal incidentalomas (AI) can be found in up to 19% of hypertensive individuals, data on the incidence of AAS in hypertensive patients with AI remain scarce. OBJECTIVE: The aim was to study adrenal aldosterone (ALD) secretory pattern in patients with adrenal adenomas with and without arterial hypertension. DESIGN AND SETTING: We conducted a case control study in a tertiary general hospital. PATIENTS AND MAIN OUTCOME MEASURES: We investigated 72 normotensive subjects with normal adrenal morphology and 191 subjects divided in three groups: 46 normotensive individuals with an AI (NAI), 89 hypertensive patients with an AI (HAI), and 56 hypertensive patients with an adrenal adenoma identified after investigation for arterial hypertension (HAA). Evaluation of autonomous cortisol secretion was based on a low-dose dexamethasone suppression test. Autonomous ALD secretion was based on a modified saline infusion test (MSI). Normal cutoff levels were obtained from the control matched population. RESULTS: Post-MSI ALD levels and the ALD/renin (REN) ratios were significantly elevated in HAI and HAA patients compared to NAI subjects. To evaluate the prevalence of AAS, we applied the combination of post-MSI ALD level and the ALD/REN ratio simultaneously (post-MSI cutoffs, ALD levels, 2.41 ng/dl; ALD/REN ratio, 0.35 ng/dl/MUU/ml). Based on these cutoffs, 12% of NAI, 36.4% of HAI, and 54.2% of HAA patients had AAS. The prevalence of autonomous cortisol secretion did not differ among the three groups. CONCLUSIONS: Using a MSI test, we found a remarkably increased prevalence of AAS in hypertensive patients with adrenal adenomas, even when the latter represented an incidental finding. PMID- 22319029 TI - Adipocytes as a source of increased circulating levels of nicotinamide phosphoribosyltransferase/visfatin in active acromegaly. AB - BACKGROUND: Nicotinamide phosphoribosyltransferase (NAMPT)/visfatin is a widely expressed protein with various effects on glucose and lipid metabolism, cell survival, and inflammation. AIM: We hypothesized that NAMPT was related to metabolic disturbances in active acromegaly. METHODS: Body composition, glucose metabolism, and NAMPT levels were measured in 47 patients with active, untreated acromegaly and 24 age-, sex-, and body mass index-matched controls. The in vitro effects of GH/IGF-I on NAMPT expression in human sc adipocytes (SCA), visceral adipocytes, osteoblasts, and hepatocytes were studied. The effects of overnight incubation with the highly specific NAMPT inhibitor FK866 on the GH-stimulated monocyte chemotactic protein-1 and IL-6 expression in mature SCA were evaluated. RESULTS: NAMPT was increased in active acromegaly (P = 0.004) and correlated negatively with limb (arms + legs) fat percentage (% fat, r = -0.32; P = 0.032). After adjusting for age, gender, leptin, and GH, the circulating NAMPT correlated negatively with limb and total body fat percentage (% fat limbs, r = -0.43, P = 0.006; % fat total body, r = -0.36, P = 0.022) and correlated positively with limb and total body lean percentage (% lean limbs, r = 0.31, P = 0.047; % lean total body, r = 0.33, P = 0.034). No correlation between NAMPT and glucose metabolic parameters was found. In vitro studies revealed that GH increased NAMPT expression in adipocytes. The inhibition of NAMPT enzymatic activity attenuated GH-induced monocyte chemotactic protein-1 expression in SCA. CONCLUSIONS: NAMPT is increased in active acromegaly and may be an inflammatory mediator that causes monocyte infiltration in adipose tissue. PMID- 22319030 TI - A concomitant false-negative 18F-FDG PET imaging in an adrenocortical carcinoma and a high uptake in a corresponding liver metastasis. PMID- 22319031 TI - Unusual complication of a pancreatic neuroendocrine tumor presenting with malignant hypercalcemia. AB - CONTEXT: Hypersecretion of PTHrP is a relatively common cause of malignancy related hypercalcemia but has only been described in a few cases of neuroendocrine tumors (NET). OBJECTIVE: The aim of this case report is to describe the clinical syndrome, complex therapeutic interventions, and unusual complications caused by persistent PTHrP hypersecretion in a patient with a pancreatic NET. CASE ILLUSTRATION: A 58-yr-old male patient presented with nonspecific abdominal pain and was found to have severe hypercalcemia secondary to a well-differentiated NET of the pancreas associated with extensive liver metastases. Elevated ionized calcium levels accompanied by low serum PTH and remarkably elevated PTHrP concentrations were consistent with PTHrP-related hypercalcemia that proved to be resistant to various chemotherapeutic regimens and supportive therapy. Partial control of the humoral syndrome was obtained only after the application of cytoreductive interventions and the introduction of various molecular targeted therapies. Due to persistent PTHrP action, bone disease emerged in the form of brown tumors. DISCUSSION: The manifestation of paraneoplastic syndrome due to PTHrP hypersecretion, despite its rareness in NET, should be considered in the differential diagnosis of hypercalcemia in such tumors. Moreover, the appearance of bone lesions in this setting may be in the context of metabolic bone disease and could be misdiagnosed as bone metastases. PMID- 22319032 TI - Serum 24,25-dihydroxyvitamin D concentrations in osteogenesis imperfecta: relationship to bone parameters. AB - BACKGROUND: Several studies suggest that 24,25-dihydroxyvitamin D [24,25(OH)2D] may have an effect on bone mass and metabolism. OBJECTIVE: We evaluated the relationship between serum 24,25(OH)2D levels and bone density and bone metabolism in children with a primary bone disorder-osteogenesis imperfecta (OI). MATERIALS AND METHODS: The study included 132 patients (age, 1.1 to 17.9 yr; 67 girls) with OI types I, III, or IV who had not received bisphosphonate treatment at the time of analysis. RESULTS: Serum 24,25(OH)2D levels were significantly higher in OI type III than in OI type I or IV. Serum 24,25(OH)2D concentrations were positively correlated with serum 25-hydroxyvitamin D (25OHD) levels and negatively correlated with serum PTH levels, and were not correlated with serum 1alpha,25-dihydroxyvitamin D [1,25(OH)2D]. The ratio between serum 24,25(OH)2D and 25OHD was negatively correlated with age and was independent of serum 25OHD concentrations. Regression analysis revealed that OI severity (P = 0.04), serum 25OHD levels (P < 0.001), and serum PTH concentrations (P = 0.045), but not age, gender, or serum 1,25(OH)2D, were independent predictors of serum 24,25(OH)2D levels. No correlation was found between serum 24,25(OH)2D levels or the ratio between serum 24,25(OH)2D and 25OHD and lumbar spine bone mineral density z scores or bone marker levels (serum osteocalcin and urinary collagen type I N telopeptide) after adjusting for OI type, age, and gender. CONCLUSION: Patients with more severe OI type had higher 24,25(OH)2D serum levels and higher serum 24,25(OH)2D to 25OHD ratios, suggesting an increased 25OHD-24-hydroxylase activity. PMID- 22319033 TI - Germline AIP mutations in apparently sporadic pituitary adenomas: prevalence in a prospective single-center cohort of 443 patients. AB - CONTEXT: Germline mutations of the AIP (aryl-hydrocarbon receptor interacting protein) gene are associated with a predisposition to pituitary adenomas. Such mutations are found in about half of patients with familial acromegaly, but penetrance is incomplete. OBJECTIVE: We studied the prevalence of germline AIP mutations in a large cohort of patients with apparently sporadic pituitary adenomas. PATIENTS AND SETTING: A total of 443 patients with pituitary adenomas of all histotypes, who had no familial history of pituitary adenomas or multiple endocrine neoplasia and who were examined at Bicetre University Hospital, a tertiary referral center, between 2007 and 2010, were enrolled in this prospective study. METHODS: The entire coding sequence of the AIP gene was screened for germline mutations. A subgroup of patients were screened for large deletions or duplications of the AIP and MEN1 genes by multiplex ligation dependent probe amplification. RESULTS: AIP mutations were detected in 16 (3.6%) of the 443 patients, comprising six of 148 patients with acromegaly (4.1%), six of 132 patients with prolactinomas (4.5%), one of 113 patients with nonfunctioning adenomas (0.9%), three of 44 patients with corticotropic adenomas (6.8%), and none of the six patients with thyrotropic adenomas. This is the first report of an AIP mutation leading to a truncated protein in a patient with Cushing's disease. Patients with AIP mutation were younger at diagnosis (24.1 vs. 42.8 yr) and had predominantly macroadenoma (12 of 16). No mutations were found in patients diagnosed after age 40 yr, whereas the prevalence before this age was 7.2% (16 of 222). Studies of seven of the AIP-mutated patients' families showed that one asymptomatic parent carried the same mutation in each case. CONCLUSION: This large prospective cohort study confirms the very low prevalence of germline AIP mutations in patients with apparently sporadic pituitary adenomas. We propose to limit AIP testing to patients diagnosed before age 40 yr with apparently sporadic large pituitary adenomas, especially GH- or PRL-secreting adenomas. PMID- 22319034 TI - Impaired incretin-induced amplification of insulin secretion after glucose homeostatic dysregulation in healthy subjects. AB - OBJECTIVE: The insulinotropic effect of the incretin hormones, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1) is impaired in patients with type 2 diabetes. It remains unclear whether this impairment is a primary pathophysiological trait or a consequence of developing diabetes. Therefore, we aimed to investigate the insulinotropic effect of GIP and GLP-1 compared with placebo before and after 12 d of glucose homeostatic dysregulation in healthy subjects. RESEARCH DESIGN AND METHODS: The insulinotropic effect was measured using hyperglycemic clamps and infusion of physiological doses of GIP, GLP-1, or saline in 10 healthy Caucasian males before and after intervention using a high-calorie diet, sedentary lifestyle, and administration of prednisolone (37.5 mg once daily) for 12 d. RESULTS: The intervention resulted in increased insulin resistance according to the homeostatic model assessment (1.2 +/- 0.2 vs. 2.6 +/- 0.5, P = 0.01), and glucose tolerance deteriorated as assessed by the area under curve for plasma glucose during a 75-g oral glucose tolerance test (730 +/- 30 vs. 846 +/- 57 mm for 2 h, P = 0.021). The subjects compensated for the change in insulin resistance by significantly increasing their postintervention insulin responses during saline infusion by 2.9 +/- 0.5 fold (P = 0.001) but were unable to do so in response to incretin hormones (which caused insignificant increases of only 1.78 +/- 0.3 and 1.38 +/- 0.3-fold, P value not significant). CONCLUSIONS: These data show that impairment of the insulinotropic effect of both GIP and GLP-1 can be induced in healthy male subjects without risk factors for type 2 diabetes, indicating that the reduced insulinotropic effect of the incretin hormones observed in type 2 diabetes most likely is a consequence of insulin resistance and glucose intolerance rather than a primary event causing the disease. PMID- 22319035 TI - Gender difference in the neuroendocrine regulation of growth hormone axis by selective estrogen receptor modulators. AB - CONTEXT: In men, GH secretion is stimulated by estradiol derived locally from aromatization of testosterone. Recently, we showed that local estrogen also plays a major role in the central regulation of GH secretion in women. Tamoxifen and raloxifene are selective estrogen receptor modulators (SERMs), drugs that block central estrogen action but exert estrogen-like effects in the liver, inhibiting hepatic IGF-I production. The relative impact of SERMs on the GH-IGF-I axis in men and women has not been investigated. OBJECTIVE: The aim of the study was to determine whether there is a gender difference in the impact of SERMs on the GH IGF-I axis. DESIGN: We conducted a comparative, randomized, open-label, crossover study of tamoxifen and raloxifene. PATIENTS AND INTERVENTION: Ten healthy postmenopausal women and ten healthy men were randomized to 2-wk sequential treatment with tamoxifen (10 and 20 mg/d) and raloxifene (60 and 120 mg/d) with a washout of 2 wk between treatments. MAIN OUTCOME MEASURES: The GH response to arginine, IGF-I, testosterone, and SHBG was measured. RESULTS: In women, but not in men, tamoxifen significantly attenuated the GH response to arginine. The GH response was not significantly blunted by raloxifene in both sexes. Both SERMs significantly reduced mean IGF-I levels to a similar degree in men and women. In men, both SERMs significantly increased LH and testosterone levels. CONCLUSIONS: In summary, GH secretion was blunted by tamoxifen in women in the face of reduced IGF-I feedback inhibition but not in men in whom the gonadal axis was stimulated. We conclude that potential blunting of GH secretion in men by SERMs was counteracted by concomitant central stimulation of GH secretion by testosterone. In therapeutic doses, tamoxifen may induce detrimental metabolic effects in women, but not men. PMID- 22319036 TI - Homozygous thyroid hormone receptor beta-gene mutations in resistance to thyroid hormone: three new cases and review of the literature. AB - CONTEXT: The most common cause of resistance to thyroid hormone (RTH) is heterozygous thyroid hormone receptor beta (THRB) gene mutations. Homozygous mutations in the THRB gene are a rare event. OBJECTIVE: In this study, the clinical findings of three new patients (belonging to two families) homozygous for mutations in the THRB gene are compared to three other families in which affected individuals lack a normal TRbeta. METHODS: We conducted clinical studies and genetic analyses. RESULTS: The clinical presentation in all three homozygous subjects was unusually severe; their phenotype was characterized by compromised intellectual development, tachycardia, goiter, growth retardation, and hearing loss. This was comparable with one other reported patient homozygous for mutant TRbeta, but not in RTH due to THRB gene deletions. CONCLUSION: We report three new subjects, from two families, in whom RTH was associated with homozygous mutations in the THRB gene. They represent an important addition to the single known patient homozygous for a mutant TRbeta. The clinical and laboratory abnormalities indicate a strong dominant-negative effect and are in agreement with data obtained from mice expressing a mutant Thrb in both alleles. This report strengthens the concept that the mutated TRbeta interferes with the function of the TRalpha1 in humans. PMID- 22319037 TI - Low 25-hydroxyvitamin D is associated with increased mortality in female nursing home residents. AB - CONTEXT: Vitamin D deficiency contributes to skeletal diseases and is highly prevalent among institutionalized elderly patients. Whether low 25-hydroxyvitamin D (25[OH]D) concentrations are an independent risk factor for mortality in these patients is, however, unclear. OBJECTIVE: We aimed to evaluate whether 25(OH)D concentrations are associated with mortality. DESIGN, SETTING, AND PARTICIPANTS: This is a prospective cohort study among elderly female patients (age >70 yr) recruited from 95 nursing homes in Austria. MAIN OUTCOME MEASURES: We calculated Cox proportional hazard ratios (HR) for all-cause mortality according to 25(OH)D quartiles. RESULTS: We examined 961 study participants (age 83.7 +/- 6.1 yr). Median 25(OH)D concentration was 17.5 (interquartile range 13.7-25.5) nmol/liter, and 93% of our cohort had 25(OH)D levels below 50 nmol/liter. During a mean follow-up time of 27 +/- 8 months, 284 patients died. Compared with the fourth quartile (25[OH]D >25.5 nmol/liter), the age-adjusted HR (with 95% confidence interval) was 1.49 (1.07-2.10) in the first 25(OH)D quartile (25[OH]D <14.0 nmol/liter), and this association remained significant after multivariate adjustments (HR = 1.56; 95% confidence interval = 1.01-2.40). CONCLUSIONS: This Austrian study suggests that the majority of institutionalized female patients are vitamin D deficient during winter and that there was an inverse association of 25(OH)D and mortality. These data underscore the urgent need for effective strategies for the prevention and treatment of vitamin D deficiency, in particular in the setting of nursing homes. PMID- 22319038 TI - Genetic overlap in Kallmann syndrome, combined pituitary hormone deficiency, and septo-optic dysplasia. AB - CONTEXT: Kallmann syndrome (KS), combined pituitary hormone deficiency (CPHD), and septo-optic dysplasia (SOD) all result from development defects of the anterior midline in the human forebrain. OBJECTIVE: The objective of the study was to investigate whether KS, CPHD, and SOD have shared genetic origins. DESIGN AND PARTICIPANTS: A total of 103 patients with either CPHD (n = 35) or SOD (n = 68) were investigated for mutations in genes implicated in the etiology of KS (FGFR1, FGF8, PROKR2, PROK2, and KAL1). Consequences of identified FGFR1, FGF8, and PROKR2 mutations were investigated in vitro. RESULTS: Three patients with SOD had heterozygous mutations in FGFR1; these were either shown to alter receptor signaling (p.S450F, p.P483S) or predicted to affect splicing (c.336C>T, p.T112T). One patient had a synonymous change in FGF8 (c.216G>A, p.T72T) that was shown to affect splicing and ligand signaling activity. Four patients with CPHD/SOD were found to harbor heterozygous rare loss-of-function variants in PROKR2 (p.R85G, p.R85H, p.R268C). CONCLUSIONS: Mutations in FGFR1/FGF8/PROKR2 contributed to 7.8% of our patients with CPHD/SOD. These data suggest a significant genetic overlap between conditions affecting the development of anterior midline in the human forebrain. PMID- 22319039 TI - Markers of recurrence and long-term morbidity in craniopharyngioma: a systematic analysis of 171 patients. AB - CONTEXT: Craniopharyngiomas are often associated with an unfavorable prognosis, but data on their long-term consequences are sparse. OBJECTIVE: The aim of the study was to identify markers of recurrence and factors associated with compromised social rehabilitation and altered quality of life in a large cohort of patients with either childhood-onset (CO) or adult-onset craniopharyngioma. METHODS: Retrospective analysis was performed for 171 patients treated for craniopharyngioma in two academic centers in France between 1972 and 2009. For each subject, data were collected concerning clinical presentation, imaging features, visual sequelae, endocrine and metabolic impact, treatment modalities (surgery, radiotherapy), recurrence-free survival rate, and social insertion, as well as answers to the WHO-QOL BREF questionnaire. RESULTS: A total of 65 CO and 106 adult-onset patients were reviewed. If CO was diagnosed before the age of 10 yr, this was associated with a higher incidence of obesity, blindness, and panhypopituitarism, and only 40.7% of subjects had adequate work or school attendance compared to 72.4% of patients with later disease onset. Initial symptoms of intracranial hypertension (SIHT), pterional surgery, and multiple surgery were associated with obesity and poorer social insertion. No determinant of quality of life was identified. In the subgroup of patients treated in the 1990s and later, the progression rate was 59.4% in patients with residual tumor on magnetic resonance imaging compared with a 19.8% recurrence rate in the group with apparently complete resection. Recurrence/progression correlates significantly with male gender, early onset (before 10 yr), and SIHT, but only SIHT at presentation remained a significant predictor with multivariate analysis. CONCLUSIONS: Craniopharyngioma continues to be associated with severe outcomes. Higher morbidity rates are found in patients with early-onset disease (before 10 yr), initial SIHT, or in whom pterional surgery was required. Markers of recurrence are difficult to identify, with SIHT being the most powerful predictor. PMID- 22319040 TI - Neurodevelopment in children born to hypothyroid mothers restored to normal thyroxine (T4) concentration by late pregnancy in Japan: no apparent influence of maternal T4 deficiency. AB - CONTEXT: The importance of maternal T4 for brain development prior to the onset of fetal thyroid function has been suggested in basic studies, and a correlation between mild maternal T4 deficiency in early gestation and disturbance of neurodevelopment in progenies has been shown in large case-control studies. These findings suggest that maternal T4 deficiency in early pregnancy potentially affects neurointellectual development. On the other hand, no apparent adverse effect in children born to mothers with overt hypothyroidism in Japan has been reported where maternal T4 had been restored to normal by late pregnancy. OBJECTIVE: We report five cases in Japan showing no apparent effect of maternal T4 deficiency on neurodevelopment in progenies where low T4 levels had been corrected by late pregnancy. METHODS: Five women with overt hypothyroidism detected at 6-16 wk gestation initiated T4 treatment. Four women restored euthyroidism by the 20th week. One remained in a subclinical hypothyroid state. Developmental scores of their children were evaluated between 25 months and 11 yr of age by either the Tsumori-Inage Infant's Developmental Test or the Wechsler Intelligence Scale for Children-Third Edition and compared to those of corresponding siblings with no exposure to maternal hypothyroidism. RESULTS: The development scores of all the children turned out to be either normal or advanced. CONCLUSIONS: In iodine-sufficient areas, maternal T4 deficiency in early pregnancy does not necessarily affect neurodevelopment. Therefore, other potential factors altering neurodevelopment, such as iodine deficiency, must be investigated. PMID- 22319041 TI - Serum level of the phosphaturic factor FGF23 is associated with abdominal aortic calcification in men: the STRAMBO study. AB - CONTEXT: Calcification inhibitor deficiencies, mineral imbalance, and phenotypic transformation of vascular cells to osteogenic cells initiate and sustain vascular calcification. Fibroblast growth factor-23 (FGF23) is a key molecule regulating mineral homeostasis. OBJECTIVE: Our objective was to assess the association of serum FGF23 levels with mineral metabolism parameters and abdominal aortic calcification (AAC) in men. DESIGN: This was a cross-sectional analysis in the STRAMBO cohort. SETTING: Men holding a private health insurance cover with Mutuelle de Travailleurs de la Region Lyonnaise were included in the study. PARTICIPANTS: Participants included male volunteers aged 20-87 (n = 1130). INTERVENTIONS: Nonfasting blood collection was done. AAC was semiquantitatively assessed from vertebral fracture assessment scans obtained using dual-energy x ray absorptiometry. MAIN OUTCOME MEASURES: We evaluated the association between FGF23 concentration and AAC severity in men. RESULTS: In 350 men aged 60 yr or younger, FGF23 levels decreased with age (r = -0.21; P < 0.001) but were not associated with any other parameter. In 780 men aged over 60 yr, serum FGF23 correlated with age (r = 0.37; P < 0.001) and, after adjustment for confounders, with glomerular filtration rate (r = -0.31; P < 0.001) and PTH levels (r = 0.25; P < 0.001). After adjustment for confounders, self-reported ischemic heart disease, diabetes mellitus as well as higher concentrations of C-reactive protein and osteoprotegerin were all associated with higher FGF23 levels. After adjustment for confounders, subjects in the highest FGF23 quartile had higher prevalence of severe AAC compared with the three lower quartiles combined (odds ratio = 1.88; 95% confidence interval = 1.22-2.85; P < 0.005). CONCLUSIONS: In healthy older men, circulating FGF23 is associated with parameters of mineral metabolism, including bone metabolism-regulating cytokines, and with severe AAC independent of traditional risk factors. PMID- 22319042 TI - Risk factors for neck nodal metastasis in papillary thyroid microcarcinoma: a study of 1066 patients. AB - CONTEXT: The surgical management of papillary thyroid microcarcinoma (PTMC), especially regarding the necessity of central lymph node dissection, remains controversial. OBJECTIVE: The objective of the study was to describe the clinicopathological features of PTMC and to identify the risk factors for central lymph node metastasis (CLNM) that can guide surgical strategies for patients with PTMC. DESIGN: In this retrospective cross-sectional study, risk factors and outcome variables were assessed at the time of surgery for the primary tumor. SETTING: The study was conducted at a university-based tertiary care cancer hospital. PATIENTS: Data from the medical records of 1066 consecutive patients diagnosed with PTMC over a 5-yr period were analyzed. RESULTS: Our multivariate logistic regression analysis found male gender, younger age (<=45 yr of age), multifocal lesions, extrathyroidal extension, and larger size of the primary tumor (>6 mm) to be associated with CLNM; multifocal lesions were associated with the highest risk (odds ratio 4.476, 95% confidence interval 2.975-6.735). Extrathyroidal extension, multifocal lesions, and CLNM were associated with lateral neck lymph node metastasis (LLNM). In patients with a solitary primary tumor, tumor location in the upper third of the thyroid lobe was associated with a lower risk of CLNM and a higher risk of LLNM. CONCLUSIONS: Prophylactic central lymph node dissection need be considered in PTMC patients presenting with risk factors. In PTMC patients with a solitary primary tumor, tumor location can assist in the evaluation of LLNM. We recommend multicenter research and long-term follow-up to better understand the risk factors and surgical management of PTMC. PMID- 22319043 TI - Relationship between MRI-measured bone marrow adipose tissue and hip and spine bone mineral density in African-American and Caucasian participants: the CARDIA study. AB - CONTEXT: An increasing number of studies suggest that bone marrow adipose tissue (BMAT) might play a role in the pathogenesis of osteoporosis. Our previous study of Caucasian women demonstrated that there is an inverse relationship between BMAT and whole-body bone mineral density (BMD). It is unknown whether visceral adipose tissue (VAT), sc adipose tissue (SAT), and skeletal muscle had an effect on the relationship between BMAT and BMD. OBJECTIVE: In the present study we investigated the relationship between pelvic, hip, and lumbar spine BMAT with hip and lumbar spine BMD in the population-based Coronary Artery Risk Development in Young Adults (CARDIA) sample with adjustment for whole-body magnetic resonance imaging (MRI)-measured VAT, SAT, and skeletal muscle. DESIGN: T1-weighted MRI was acquired for 210 healthy African-American and Caucasian men and women (age 38-52 yr). Hip and lumbar spine BMD were measured by dual-energy x-ray absorptiometry. RESULTS: Pelvic, hip, and lumbar spine BMAT had negative correlations with hip and lumbar spine BMD (r = -0.399 to -0.550, P < 0.001). The inverse associations between BMAT and BMD remained strong after adjusting for demographics, weight, skeletal muscle, SAT, VAT, total adipose tissue (TAT), menopausal status, lifestyle factors, and inflammatory markers (standardized regression coefficients = -0. 296 to -0.549, P < 0.001). Among body composition measures, skeletal muscle was the strongest correlate of BMD after adjusting for BMAT (standardized regression coefficients = 0.268-0.614, P < 0.05), with little additional contribution from weight, SAT, VAT, or total adipose tissue. CONCLUSION: In this middle-aged population, a negative relationship existed between MRI-measured BMAT and hip and lumbar spine BMD independent of demographics and body composition. These observations support the growing evidence linking BMAT with low bone density. PMID- 22319044 TI - ATLANTIC-DIP: raised maternal body mass index (BMI) adversely affects maternal and fetal outcomes in glucose-tolerant women according to International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. AB - CONTEXT: Raised maternal body mass index (BMI) in association with hyperglycemia is associated with adverse pregnancy outcome. The contribution of raised BMI as an independent risk factor for adverse pregnancy outcome is of growing concern and increasing prevalence. OBJECTIVE: The aim of this study was to investigate the effects of raised maternal BMI on pregnancy outcome in glucose-tolerant women using the International Association of Diabetes and Pregnancy Study Groups criteria. PARTICIPANTS AND SETTING: We studied a cohort of glucose-tolerant, pregnant women (n = 3656) who were attending antenatal obstetric clinics and were recruited to a universal screening program for gestational diabetes under the ATLANTIC-DIP partnership. DESIGN: We conducted a prospective observational study of pregnancy outcome. Maternal outcomes include glucose, delivery mode, pregnancy induced hypertension, preeclampsia, antepartum hemorrhage, and postpartum hemorrhage. Fetal outcomes included birthweight, congenital malformation, fetal death, neonatal jaundice, hypoglycemia, and respiratory distress. RESULTS: Increasing maternal BMI was associated with adverse pregnancy outcomes: higher cesarean section rates, preeclampsia, pregnancy-induced hypertension, increased birth weight, and congenital malformation. The association of glucose with adverse pregnancy outcome was weak and did not interact with raised BMI. A BMI threshold of 28 kg/m(2) was associated with a significant rise in adverse pregnancy outcome. CONCLUSIONS: Raised maternal BMI, within the overweight range, is associated with adverse pregnancy outcomes. These adverse effects of BMI occur independently of maternal glucose. It is apparent that pregnancy unmasks an underlying unhealthy metabolic milieu in obese and overweight women. PMID- 22319045 TI - Association of leukocyte telomere length with type 2 diabetes in mainland Chinese populations. AB - CONTEXT: Telomeres are structures at the ends of eukaryotic chromosomes. They help maintain genomic stability. High oxidative stress can lead to accelerated telomere shortening, which causes premature cell senescence. This is implicated in the development of type 2 diabetes (T2D). For this reason, we hypothesize that telomere shortening can characterize T2D. METHODS: We investigated the association between leukocyte telomere length (LTL) and T2D in a retrospective case-control study with a sample of 4016 Chinese Han subjects (1936 unrelated T2D cases and 2080 controls). Logistic regression analysis was performed to evaluate the association between LTL and T2D, adjusted for age and gender. Multivariate linear regression analysis was used to test for any association of LTL with a number of clinical, demographic, and diabetes-associated variables. RESULTS: Telomere repeat length (T)/copy number of a single-copy gene (S) ratios (T/S) of LTL were found to be significantly shorter in T2D cases [1.00 T/S, 95% confidence interval (CI) = 0.99-1.02] compared with controls (1.08 T/S, 95% CI = 1.06-1.09) over a wide age range (odds ratio of diabetes for a 1-U decrease in ln transformed TL = 1.52; 95% CI = 1.23-1.88; P = 0.0001). CONCLUSION: Our research demonstrates association between shorter LTL and T2D in a population from mainland China. Our study suggests that shorter LTL might be associated with T2D in a manner independent of smoking and drinking habits or the time of T2D onset time. PMID- 22319046 TI - Cerebral perturbations during exercise in hypoxia. AB - Reduction of aerobic exercise performance observed under hypoxic conditions is mainly attributed to altered muscle metabolism due to impaired O(2) delivery. It has been recently proposed that hypoxia-induced cerebral perturbations may also contribute to exercise performance limitation. A significant reduction in cerebral oxygenation during whole body exercise has been reported in hypoxia compared with normoxia, while changes in cerebral perfusion may depend on the brain region, the level of arterial oxygenation and hyperventilation induced alterations in arterial CO(2). With the use of transcranial magnetic stimulation, inconsistent changes in cortical excitability have been reported in hypoxia, whereas a greater impairment in maximal voluntary activation following a fatiguing exercise has been suggested when arterial O(2) content is reduced. Electromyographic recordings during exercise showed an accelerated rise in central motor drive in hypoxia, probably to compensate for greater muscle contractile fatigue. This accelerated development of muscle fatigue in moderate hypoxia may be responsible for increased inhibitory afferent signals to the central nervous system leading to impaired central drive. In severe hypoxia (arterial O(2) saturation <70-75%), cerebral hypoxia per se may become an important contributor to impaired performance and reduced motor drive during prolonged exercise. This review examines the effects of acute and chronic reduction in arterial O(2) (and CO(2)) on cerebral blood flow and cerebral oxygenation, neuronal function, and central drive to the muscles. Direct and indirect influences of arterial deoxygenation on central command are separated. Methodological concerns as well as future research avenues are also considered. PMID- 22319047 TI - Renal responses to furosemide are significantly attenuated in male sheep at 6 months of age following fetal uninephrectomy. AB - We have previously shown that fetal uninephrectomy (uni-x) at 100 days of gestation (term = 150 days) in male sheep results in a 30% nephron deficit, reduction in glomerular filtration rate (GFR) and renal blood flow, and elevation in arterial pressure at 6 mo of age. Furthermore, in response to an acute 0.9% saline load, sodium excretion was significantly delayed in uni-x animals leading us to speculate that tubuloglomerular feedback (TGF) activity was reset in uni-x animals. In the present study, we induced TGF blockade by furosemide administration (1.5 mg/kg iv over 90 min) and determined GFR, effective renal plasma flow, and urine and sodium excretion responses in 6-mo-old male sheep. In response to furosemide, a significant diuresis and natriuresis was observed in the sham group; however, the response was significantly delayed and reduced in uni-x animals (both, P(treatment*time) < 0.001). Cummulative urinary and sodium output was significantly less in the uni-x compared with the sham sheep (both, P(treatment*time) < 0.001). GFR was increased in the sham but not the uni-x sheep (P(treatment*time) < 0.0001). In conclusion, the excretory response to furosemide was attenuated in the uni-x sheep, and this suggests a rightward resetting of the TGF operating point. The TGF mechanism is important in the fine tuning of sodium homeostasis and is likely a contributing factor for the dysfunction in sodium regulation we have previously observed in the uni-x animals. PMID- 22319048 TI - Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice. AB - Consumption of high levels of fructose in humans and animals leads to metabolic and cardiovascular dysfunction. There are questions as to the role of the autonomic changes in the time course of fructose-induced dysfunction. C57/BL male mice were given tap water or fructose water (100 g/l) to drink for up to 2 mo. Groups were control (C), 15-day fructose (F15), and 60-day fructose (F60). Light dark patterns of arterial pressure (AP) and heart rate (HR), and their respective variabilities were measured. Plasma glucose, lipids, insulin, leptin, resistin, adiponectin, and glucose tolerance were quantified. Fructose increased systolic AP (SAP) at 15 and 60 days during both light (F15: 123 +/- 2 and F60: 118 +/- 2 mmHg) and dark periods (F15: 136 +/- 4 and F60: 136 +/- 5 mmHg) compared with controls (light: 111 +/- 2 and dark: 117 +/- 2 mmHg). SAP variance (VAR) and the low-frequency component (LF) were increased in F15 (>60% and >80%) and F60 (>170% and >140%) compared with C. Cardiac sympatho-vagal balance was enhanced, while baroreflex function was attenuated in fructose groups. Metabolic parameters were unchanged in F15. However, F60 showed significant increases in plasma glucose (26%), cholesterol (44%), triglycerides (22%), insulin (95%), and leptin (63%), as well as glucose intolerance. LF of SAP was positively correlated with SAP. Plasma leptin was correlated with triglycerides, insulin, and glucose tolerance. Results show that increased sympathetic modulation of vessels and heart preceded metabolic dysfunction in fructose-consuming mice. Data suggest that changes in autonomic modulation may be an initiating mechanism underlying the cluster of symptoms associated with cardiometabolic disease. PMID- 22319050 TI - Hormonal responses to extreme fasting in subantarctic fur seal (Arctocephalus tropicalis) pups. AB - Surviving prolonged fasting implies closely regulated alterations in fuel provisioning to meet metabolic requirements, while preserving homeostasis. Little is known, however, of the endocrine regulations governing such metabolic adaptations in naturally fasting free-ranging animals. The hormonal responses to natural prolonged fasting and how they correlate to the metabolic adaptations observed, were investigated in subantarctic fur seal (Arctocephalus tropicalis) pups, which, because of the intermittent pattern of maternal attendance, repeatedly endure exceptionally long fasting episodes throughout their development (1-3 mo). Phase I fasting was characterized by a dramatic decrease in plasma insulin, glucagon, leptin, and total l-thyroxine (T(4)) associated with reductions in mass-specific resting metabolic rate (RMR), plasma triglycerides, glycerol, and urea-to-creatine ratio, while nonesterified fatty acids (NEFA) and beta-OHB increased. In contrast, the metabolic steady-state of phase II fasting reached within 6 days was associated with minimal concentrations of insulin, glucagon, and leptin; unchanged cortisol and triiodothyronine (T(3)); and moderately increased T(4). The early fall in insulin and leptin may mediate the shift to the strategy of energy conservation, protein sparing, and primary reliance on body lipids observed in response to the cessation of feeding. In contrast to the typical mammalian starvation response, nonelevated cortisol and minimal glucagon levels may contribute to body protein preservation and downregulation of catabolic pathways, in general. Furthermore, thyroid hormones may be involved in a process of energy conservation, independent of pups' nutritional state. These original hormonal settings might reflect an adaptation to the otariid repeated fasting pattern and emphasize the crucial importance of a tight physiological control over metabolism to survive extreme energetic constraints. PMID- 22319049 TI - Homeostatic regulation of protein intake: in search of a mechanism. AB - Free-living organisms must procure adequate nutrition by negotiating an environment in which both the quality and quantity of food vary markedly. Recent decades have seen marked progress in our understanding of neural regulation of feeding behavior. However, this progress has occurred largely in the context of energy intake, despite the fact that food intake is influenced by more than just the energy content of the diet. A large number of behavioral studies indicate that both the quantity and quality of dietary protein can markedly influence food intake. High-protein diets tend to reduce intake, low-protein diets tend to increase intake, and rodent models seem to self-select between diets in order to meet protein requirements and avoid diets that are imbalanced in amino acids. Recent work suggests that the amino acid leucine regulates food intake by altering mTOR and AMPK signaling in the hypothalamus, while activation of GCN2 within the anterior piriform cortex contributes to the detection and avoidance of amino acid-imbalanced diets. This review focuses on the role that these and other signaling systems may play in mediating the homeostatic regulation of protein balance, and in doing so, highlights our lack of knowledge regarding the physiological and neurobiological mechanisms that might underpin such a regulatory phenomenon. PMID- 22319051 TI - Glycerol uptake is by passive diffusion in the heart but by facilitated transport in RBCs at high glycerol levels in cold acclimated rainbow smelt (Osmerus mordax). AB - Rainbow smelt (Osmerus mordax) is a small fish that accumulates glycerol at low winter seawater temperatures. In laboratory-held fish, glycerol concentration typically reaches 225 mM in plasma and in all cells. Glycerol uptake by the heart and red blood cells (RBCs) was assessed by tracking [(14)C(U)]glycerol into the acid-soluble pool. In fish acclimated to 9-10 degrees C a decrease in perfusion/incubation temperature from 8 to 1 degrees C resulted in a decrease in glycerol uptake with a Q(10) of 3.2 in heart and 2.4 in RBCs. Acclimation to ~1.5 degrees C did not result in an adaptive enhancement of glycerol uptake as rates were unchanged in heart and RBCs. Glycerol uptake at 1 degrees C was by passive diffusion in heart as evidenced by a linear relationship between glycerol uptake and extracellular glycerol concentration and a lack of inhibition by phloretin. In contrast, in RBCs, glycerol uptake with respect to glycerol concentration showed two linear relationships with a transition point around 50 mM extracellular glycerol. The slope of the second phase was much steeper and eliminated with the inclusion of phloretin. In RBCs from Atlantic salmon (Salmo salar), a related species that does not accumulate glycerol, glycerol uptake showed only a single linear curve and was not inhibited by phloretin. The data imply a strong facilitated component to glycerol uptake in rainbow smelt RBCs at high glycerol concentrations. We propose this is related to cyclic changes in RBC glycerol content involving a loss of glycerol at the gill and a reaccumulation during passage through the liver. PMID- 22319052 TI - Initial steps of photosystem II de novo assembly and preloading with manganese take place in biogenesis centers in Synechocystis. AB - In the cyanobacterium Synechocystis sp PCC 6803, early steps in thylakoid membrane (TM) biogenesis are considered to take place in specialized membrane fractions resembling an interface between the plasma membrane (PM) and TM. This region (the PratA-defined membrane) is defined by the presence of the photosystem II (PSII) assembly factor PratA (for processing-associated TPR protein) and the precursor of the D1 protein (pD1). Here, we show that PratA is a Mn(2+) binding protein that contains a high affinity Mn(2+) binding site (K(d) = 73 MUM) and that PratA is required for efficient delivery of Mn(2+) to PSII in vivo, as Mn(2+) transport is retarded in pratA(-). Furthermore, ultrastructural analyses of pratA(-) depict changes in membrane organization in comparison to the wild type, especially a semicircle-shaped structure, which appears to connect PM and TM, is lacking in pratA(-). Immunogold labeling located PratA and pD1 to these distinct regions at the cell periphery. Thus, PratA is necessary for efficient delivery of Mn(2+) to PSII, leading to Mn(2+) preloading of PSII in the periplasm. We propose an extended model for the spatial organization of Mn(2+) transport to PSII, which is suggested to take place concomitantly with early steps of PSII assembly in biogenesis centers at the cell periphery. PMID- 22319053 TI - PPR2263, a DYW-Subgroup Pentatricopeptide repeat protein, is required for mitochondrial nad5 and cob transcript editing, mitochondrion biogenesis, and maize growth. AB - RNA editing plays an important role in organelle gene expression in various organisms, including flowering plants, changing the nucleotide information at precise sites. Here, we present evidence that the maize (Zea mays) nuclear gene Pentatricopeptide repeat 2263 (PPR2263) encoding a DYW domain-containing PPR protein is required for RNA editing in the mitochondrial NADH dehydrogenase5 (nad5) and cytochrome b (cob) transcripts at the nad5-1550 and cob-908 sites, respectively. Its putative ortholog, MITOCHONDRIAL EDITING FACTOR29, fulfills the same role in Arabidopsis thaliana. Both the maize and the Arabidopsis proteins show preferential localization to mitochondria but are also detected in chloroplasts. In maize, the corresponding ppr2263 mutation causes growth defects in kernels and seedlings. Embryo and endosperm growth are reduced, leading to the production of small but viable kernels. Mutant plants have narrower and shorter leaves, exhibit a strong delay in flowering time, and generally do not reach sexual maturity. Whereas mutant chloroplasts do not have major defects, mutant mitochondria lack complex III and are characterized by a compromised ultrastructure, increased transcript levels, and the induction of alternative oxidase. The results suggest that mitochondrial RNA editing at the cob-908 site is necessary for mitochondrion biogenesis, cell division, and plant growth in maize. PMID- 22319054 TI - Somatic and reproductive cell development in rice anther is regulated by a putative glutaredoxin. AB - The switch from mitosis to meiosis is one of the most pivotal events in eukaryotes undergoing sexual reproduction. However, the mechanisms orchestrating meiosis initiation remain elusive, particularly in plants. Flowering plants are heterosporous, with male and female spore genesis adopting different developmental courses. We show here that plant pollen mother cells contain a specific meiosis initiation machinery through characterization of a rice (Oryza sativa) gene, MICROSPORELESS1 (MIL1). The mil1 mutant does not produce microspores in anthers but has the normal female fertility. Detailed molecular and cytological investigations demonstrate that mil1 anthers are defective in the meiotic entry of sporogenous cell progenies and in the differentiation of surrounding somatic cell layers, resulting in locules filled with somatic cells instead of microspores. Furthermore, analysis of mil1 msp1 double mutants reveals that due to the absence of MIL1, the cells in their anther locule center do not activate meiotic cell cycle either, generating a similar anther phenotype to mil1. MIL1 encodes a plant-specific CC-type glutaredoxin, which could interact with TGA transcription factors. These results suggest meiotic entry in microsporocytes is directed by an anther-specific mechanism, which requires MIL1 activity, and redox regulation might play important roles in this process. PMID- 22319055 TI - Analysis of the Arabidopsis shoot meristem transcriptome during floral transition identifies distinct regulatory patterns and a leucine-rich repeat protein that promotes flowering. AB - Flowering of Arabidopsis thaliana is induced by exposure to long days (LDs). During this process, the shoot apical meristem is converted to an inflorescence meristem that forms flowers, and this transition is maintained even if plants are returned to short days (SDs). We show that exposure to five LDs is sufficient to commit the meristem of SD-grown plants to flower as if they were exposed to continuous LDs. The MADS box proteins SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) and FRUITFULL (FUL) play essential roles in this commitment process and in the induction of flowering downstream of the transmissible FLOWERING LOCUS T (FT) signal. We exploited laser microdissection and Solexa sequencing to identify 202 genes whose transcripts increase in the meristem during floral commitment. Expression of six of these transcripts was tested in different mutants, allowing them to be assigned to FT-dependent or FT-independent pathways. Most, but not all, of those dependent on FT and its paralog TWIN SISTER OF FT (TSF) also relied on SOC1 and FUL. However, this dependency on FT and TSF or SOC1 and FUL was often bypassed in the presence of the short vegetative phase mutation. FLOR1, which encodes a leucine-rich repeat protein, was induced in the early inflorescence meristem, and flor1 mutations delayed flowering. Our data contribute to the definition of LD-dependent pathways downstream and in parallel to FT. PMID- 22319056 TI - Pre-existent Hsp72 contributes to glutamine-induced hepatic hsp72 gene activation during heat shock recovery period in rat. AB - SCOPE: Functional maintenance of liver is very important at all times for personal health. Hsp induction is associated with the protection of the organ. Glutamine, a nutrient inducer of Hsps, enhances cellular survival via Hsp72 induction in several organs, but not in the liver. The present study showed a novel approach to facilitate glutamine-induced hepatic Hsp72 synthesis and its possible mechanisms were discussed. METHODS AND RESULTS: Sprague-Dawley rats were used as the experimental animals and the livers were the targets. Glutamine was administered via tail-vein injection, and its effects on hsp72 gene activation, including Hsp72 expression, heat shock factor-1 (HSF-1) phosphorylation and DNA binding activation, were evaluated. The results showed that Hsp72 itself played a critical role in glutamine-induced hepatic Hsp72 synthesis during HS recovery period in a dose-dependent manner of preexistent Hsp72. The peak value of HSF-1 phosphorylation, HSF-1 DNA-binding activity, hsp72 mRNA accumulation, and Hsp72 synthesis was detected at 8 h after glutamine administration. CONCLUSION: Glutamine switched on alteration pathway in inducing hsp72 gene activation. The existence of Hsp72 plays a critical role in the reactivation of hsp72 gene. Glutamine sustained the induction of intracellular Hsp72, which could be beneficial in protecting the liver from various injuries. PMID- 22319058 TI - Glycosphingolipid profile of the apical pole of human placental capillaries: the relevancy of the observed data to Fabry disease. AB - A series of six full-term placentas and umbilical cords were examined using the in situ detection of globotriaosylceramide (Gb3Cer), GM1 ganglioside (GM1), GM3 ganglioside (GM3), cholesterol and caveolin 1. Immunohistochemical study showed uniform distinct staining of the apical membrane of villous capillary endothelial cells for Gb3Cer, GM1, GM3 and cholesterol. There was also a strong signal for caveolin 1. The immunophenotype suggests the presence of caveola-associated raft microdomains. The immunophenotype was almost completely shared with the extravillous intravascular trophoblast in the basal plate. It was absent in the endothelial cells of umbilical vessels and in the capillaries of somatic structures (heart, lung, skeletal muscle and skin) in neonates as well as in adults, including capillaries of the proliferative endometrium. Results of in situ analyses were confirmed by lipid chromatographic analysis of tissue homogenates and by tandem mass spectrometry. Lysosomal Gb3Cer turnover was followed in three placentas including umbilical cords from Fabry disease (alpha galactosidase A deficiency). Lysosomal storage was restricted to vascular smooth muscle cells and to endothelial cells of umbilical vessels. Placental villous capillary endothelial cells displaying a strong non-lysosomal staining for Gb3Cer were free of lysosomal storage. PMID- 22319059 TI - Cross talk between primary human renal tubular cells and endothelial cells in cocultures. AB - Interactions between renal tubular epithelial cells and adjacent endothelial cells are essential for normal renal functions but also play important roles in renal disease and repair. Here, we investigated cocultures of human primary renal proximal tubular cells (HPTC) and human primary endothelial cells to address the cross talk between these cell types. HPTC showed improved proliferation, marker gene expression, and enzyme activity in cocultures. Also, the long-term maintenance of epithelia formed by HPTC was improved, which was due to the secretion of transforming growth factor-beta1 and its antagonist alpha2 macroglobulin. HPTC induced endothelial cells to secrete increased amounts of these factors, which balanced each other functionally and only displayed in combination the observed positive effects. In addition, in the presence of HPTC endothelial cells expressed increased amounts of hepatocyte growth factor and vascular endothelial growth factor, which have well-characterized effects on renal tubular epithelial cells as well as on endothelial cells. Together, the results showed that HPTC stimulated endothelial cells to express a functionally balanced combination of various factors, which in turn improved the performance of HPTC. The results give new insights into the cross talk between renal epithelial and endothelial cells and suggest that cocultures could be also useful models for the analysis of cellular communication in renal disease and repair. Furthermore, the characterization of defined microenvironments, which positively affect HPTC, will be helpful for improving the performance of this cell type in in vitro applications including in vitro toxicology and kidney tissue engineering. PMID- 22319060 TI - Therapeutic Environments and the Religious Society of Friends. AB - The work of members of the Religious Society of Friends, also known as Quakers, in therapeutic environments has often been commented on but not discussed in detail. While several of the pioneers of planned environment therapy, therapeutic education and therapeutic communities have discussed their Quaker faith in the context of their work, very little of the practical role of Quaker governors and trustees for therapeutic environments has been written about. This paper aims to explore some of the reasons why therapeutic environment work and Quaker principles are compatible, and how Quakers and non-Quakers have been able to work together to establish and maintain effective social-based methods of therapy and management. PMID- 22319061 TI - Alcohol use and health-related quality of life among hospital outpatients in South Africa. AB - AIMS: This study examined the association of alcohol use and health-related quality of life (HRQOL) in a clinic population in South Africa. METHODS: A probability sample of 1532 (56.4% men and women 43.6%) patients from different hospital outpatient departments completed the Alcohol Use Disorder Identification Test and the social functioning (SF)-12 Health Survey. Physical and Mental Health Component Summaries and primary scales of the SF-12 were used as measures of HRQOL. RESULTS: The study did not find a significant association between alcohol use disorders and HRQoL [Physical Component Summary (PCS) and Mental health Component Summary (MCS)] in this clinic population. However, probable alcohol dependence was associated with poorer quality of life in three areas of functioning measured by the SF-12 (physical functioning, general health and mental health) compared with patients not meeting the criteria of alcohol dependence. The magnitude of the decrement in the PCS and MCS for daily or almost daily tobacco use, severe psychological distress and the number of other chronic conditions was significantly greater than for alcohol abuse or dependence. CONCLUSION: It appears that hospital outpatients in this study did not experience a diminished quality of life related to their alcohol use compared with other attenders at these clinics. Also, intervention studies with hazardous drinkers may not be able to identify treatment-related changes in global HRQoL. PMID- 22319062 TI - Tissue factor pathway inhibitor in paediatric patients with nephrotic syndrome. AB - BACKGROUND: Tissue factor pathway inhibitor is an endogenous protease inhibitor that regulates the initiation of the extrinsic coagulation pathway by producing factor Xa-mediated feedback inhibition of the tissue factor/factor VIIa (TF/VIIA) catalytic complex. OBJECTIVES: To evaluate plasma TFPI levels in paediatric patients with nephrotic syndrome and its correlation with disease activity. SUBJECTS AND METHODS: Fifteen nephrotic patients in relapse (proteinuria>40mg/m2/hour, hypoalbuminemia, and edema) before initiating steroid therapy (Group I), and another15 nephrotic patients in remission after withdrawal of steroid therapy (Group II) were compared to 15 age- and sex-matched healthy children (Group III). Besides clinical evaluation and routine laboratory investigations of nephrotic syndrome, tissue factor pathway inhibitor levels in plasma were measured by ELISA. RESULTS: Plasma TFPI level was higher in nephrotic patients during relapse (Group I) and during remission (Group II) [102.53+/-14.23 and 82.93+/-3.83ng/ml respectively] compared to that in the control group (62.40 +/- 7.53 ng/ml) (p< 0.0001). In children with nephrotic syndrome Plasma TFPI level was higher during relapse (Group I) compared to that in remission (Group II) (p< 0.0001). There was a negative correlation between plasma TFPI level and total protein and serum albumin, and there was a positive correlation between plasma TFPI level and urine protein /creatinine ratio with a statistically significant difference (p< 0.05). CONCLUSION: Nephrotic syndrome was associated with increased level of plasma tissue factor pathway inhibitor in comparison to control group and the increase was more apparent in patients with active disease. PMID- 22319063 TI - Vascular tissue reaction to acute malapposition in human coronary arteries: sequential assessment with optical coherence tomography. AB - BACKGROUND: The vascular tissue reaction to acute incomplete stent apposition (ISA) is not well known. The aim of this study was to characterize the vascular response to acute ISA in vivo and to look for predictors of incomplete healing. METHODS AND RESULTS: Optical coherence tomography studies of 66 stents of different designs, implanted in 43 patients enrolled in 3 randomized trials, were analyzed sequentially after implantation and at 6 to 13 months. Seventy-eight segments with acute ISA were identified in 36 of the patients and matched with the follow-up study by use of fiduciary landmarks. The morphological pattern of healing in the ISA segments was categorized as homogeneous, layered, crenellated, bridged, partially bridged, or bare, depending on the persistence of ISA and on the coverage. After 6 months, acute ISA volume decreased significantly, and 71.5% of the ISA segments were completely integrated into the vessel wall. Segments with acute ISA had higher risk of delayed coverage than well-apposed segments (relative risk 2.37, 95% confidence interval 2.01-2.78). Acute ISA size (estimated as ISA volume or maximum ISA distance per strut) was an independent predictor of ISA persistence and of delayed healing at follow-up. CONCLUSIONS: Neointimal healing tends to reduce ISA, with the malapposed stent struts often integrated completely into the vessel wall, resulting in characteristic morphological patterns. Coverage of ISA segments is delayed with respect to well apposed segments. The larger the acute ISA, the greater the likelihood of persistent malapposition at follow-up and delayed healing. PMID- 22319064 TI - Prehospital abciximab in ST-segment elevation myocardial infarction: results of the randomized, double-blind MISTRAL study. AB - BACKGROUND: The value of prehospital initiation of glycoprotein IIb/IIIa inhibitors remains a controversial issue. We sought to investigate whether in ambulance initiation of abciximab in patients with ST-segment elevation myocardial infarction (STEMI) improves ST-segment elevation resolution (STR) after primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: MISTRAL (Myocardial Infarction with ST-elevation Treated by Primary Percutaneous Intervention Facilitated by Early Reopro Administration in Alsace) is a prospective, randomized, double-blind study. Two hundred and fifty-six patients with acute STEMI were allocated to receive abciximab either in the ambulance (ambulance group, n=127) or in the catheterization laboratory (hospital group, n=129). The primary end point was complete (>70%) STR after PCI. Complete STR was not significantly different between the 2 groups (before PCI, 21.6% versus 15.5%, P=0.28; after PCI, 70.3% versus 65.8%, P=0.49). Thrombolysis In Myocardial Infarction (TIMI) 2 to 3 flow rates before PCI tended to be higher in the ambulance group (46.8% versus 35%, P=0.08) but not after PCI (70.3% versus 65.8%, P=0.49). Slow flow tended to be lower (5.6% versus 13.4%, P=0.07), and distal embolization occurred significantly less often in the ambulance group (8.1% versus 21.1%, P=0.008). One- and 6-month major adverse cardiac event rates were low and similar in both groups. CONCLUSIONS: Early ambulance administration of abciximab in STEMI did not improve either STR or TIMI flow rate after PCI. However, it tended to improve TIMI flow pre-PCI and decreased distal embolization during procedure. Larger studies are needed to confirm these results. PMID- 22319065 TI - Percutaneous femoral arteriovenous shunt creation for advanced chronic obstructive pulmonary disease: a single-center safety and efficacy study. AB - BACKGROUND: Advanced chronic obstructive pulmonary disease causes a significant reduction in functional capacity because of dyspnea and fatigue, partially related to hypoxemia and compromised oxygen delivery. Percutaneous creation of an arteriovenous shunt may increase oxygen delivery and, hence, improve patients' functional capacity. METHODS AND RESULTS: This is a prospective, single-center, proof-of-concept pilot study. Patients with advanced chronic obstructive pulmonary disease underwent percutaneous arteriovenous shunt creation. End points were the change in 6-minute walking distance; quality of life, measured by St George's Respiratory Questionnaire; and physiological parameters at 12-week follow-up. Fifteen patients underwent percutaneous arteriovenous shunt creation. Cardiac output and oxygen delivery increased significantly from 4.1 L/min at baseline to 5.9 L/min at 12 weeks (P<0.01) and from 751 mL/min at baseline to 972 mL/min at 12 weeks (P<0.01), respectively; however, there was a trend toward a significant decrease in the 6-minute walking distance between baseline (338 m) and 12-week follow-up (294 m) (P=0.07). There was no significant difference in the St George's Respiratory Questionnaire score, oxygen saturation, or lung function tests. Lower extremity edema, venous stenosis, right heart failure, and deep venous thrombosis occurred in 10, 7, 4, and 4 patients, respectively. CONCLUSIONS: Though it causes a significant increase in cardiac output and oxygen delivery , the creation of an arteriovenous shunt in the setting of severe chronic obstructive pulmonary disease did not improve functional capacity or quality of life. A significant number of adverse events occurred. This concept cannot be recommended for routine clinical use in unselected patients with advanced chronic obstructive pulmonary disease. PMID- 22319066 TI - Is there a clinically significant interaction between calcium channel antagonists and clopidogrel?: results from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial. AB - BACKGROUND: Clopidogrel is an inactive prodrug; it is converted to its active metabolite through the cytochrome P450 (CYP3A4) pathway, which also metabolizes calcium channel blockers (CCBs). Several studies have reported that CCBs reduce the ability of clopidogrel to inhibit platelet aggregability; one suggested that CCBs reduce the efficacy of clopidogrel. METHODS AND RESULTS: We performed a post hoc analysis of the Clopidogrel for the Reduction of Events During Observation (CREDO) study to compare the treatment effect of clopidogrel in patients on CCBs versus not on CCBs. In CREDO, 2116 patients were randomly assigned to pretreatment with 300 mg clopidogrel 3-24 hours before a planned percutaneous coronary intervention followed by 1 year of 75 mg/d clopidogrel, versus 75 mg clopidogrel at the time of the procedure and continued for 28 days only. The primary end points were a combined end point of death, myocardial infarction, and stroke at 28 days and 1 year. Among the 580 patients (27%) on CCBs at enrollment, at 28 days, the combined end point was reached in 17 patients (6%) on clopidogrel versus 28 (9%) on placebo (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.39-1.29). At 1 year, the combined end point was reached in 27 patients (10%) on clopidogrel versus 46 (15%) on placebo (HR, 0.68; 95% CI, 0.42-1.09). The treatment effect of clopidogrel was similar in patients not on CCBs at 1 year (HR, 0.78; 95% CI, 0.56-1.09). After adjustment for differences between patients on and not on CCB, there was still no evidence of an interaction between clopidogrel treatment and CCB (HR for patients not on CCBs, 0.87; 95% CI, 0.62 1.23; HR for patients on CCBs, 0.74; 95% CI, 0.45-1.21). CONCLUSIONS: In CREDO, there was no evidence that CCBs decrease the efficacy of clopidogrel. PMID- 22319067 TI - Long-term clinical outcome after fractional flow reserve-guided percutaneous coronary revascularization in patients with small-vessel disease. AB - BACKGROUND: Small coronary vessels supply small myocardial territories. The clinical significance of small-vessel stenoses is therefore questionable. Moreover, percutaneous coronary intervention (PCI) of nonfunctionally significant lesions does not improve clinical outcome and might be associated with potential procedural or stent related risks. The aim of this study was to assess the clinical outcome of fractional flow reserve (FFR)-guided PCI in the treatment of small coronary vessel lesions as compared with an angio-guided PCI. METHODS AND RESULTS: From January 2004 to December 2008, all patients treated with PCI for stable or unstable angina in small native coronary vessels (reference vessel diameter and stent size <3 mm) were retrospectively analyzed. Patients were divided into angio-guided and an FFR-guided PCI groups. A total of 717 patients were enrolled (495 angio-guided, 222 FFR-guided). End points were death, nonfatal myocardial infarction (MI), combined death or nonfatal MI, target vessel revascularization (TVR), and procedure costs. Major adverse cardiac events (MACE) were defined as death, nonfatal MI, and TVR. Clinical follow-up was obtained in 97.5% (median follow-up: 3.3 [from 0.01-5] years) of the patients. Seventy-eight patients (35%) had a significant FFR (<0.80) and underwent PCI. Using a propensity score adjusted Cox analysis, patients treated with FFR-guided PCI had significantly lower combined death or nonfatal MI (hazard ratio [HR], 0.413; 95% confidence interval [CI], 0.227-0.750; P=0.004), nonfatal MI (HR, 0.063; 95% CI, 0.009-0.462; P=0.007), TVR (HR, 0.517; 95% CI, 0.323-0.826; P=0.006), and MACE (HR, 0.458; 95% CI, 0.310-0.679; P<0.001). No difference was observed in mortality alone (HR, 0.684; 95% CI, 0.355-1.316; P=0.255). Procedure costs were also reduced in the FFR guided strategy (3253+/-102 Euros versus 4714+/-37 Euros, P<0.0001). CONCLUSIONS: FFR-guided PCI of small coronary arteries is safe and results in better clinical outcomes when compared with an angio-guided PCI. PMID- 22319068 TI - When collateral supply is accounted for epicardial stenosis does not increase microvascular resistance. AB - BACKGROUND: The relationship between epicardial stenosis and microvascular resistance remains controversial. Exploring the relationship is critical, as many tools used in interventional cardiology imply minimal and constant resistance. However, variable collateralization may impact well on these measures. We hypothesized that when collateral supply was accounted for, microvascular resistance would be independent of epicardial stenosis. METHODS AND RESULTS: Forty patients with stable angina were studied before and following percutaneous intervention. A temperature and pressure sensing guide wire was used to derive microvascular resistance using the index of microcirculatory resistance (IMR), defined as the hyperemic distal pressure multiplied by the hyperemic mean transit time. Lesion severity was assessed using fractional flow reserve. For comparison, evaluation of an angiographically normal reference vessel from the same subject also was undertaken. Both simple IMR (sIMR) and IMR corrected for collateral flow (cIMR) were calculated. When collateral supply was not accounted for, there was a significant difference in IMR values between the culprit, the post PCI, and nonculprit values (culprit sIMR 26.68+/-2.06, nonculprit sIMR 18.37+/-1.89, P=0.002; post percutaneous intervention sIMR 18.5+/-1.94 versus culprit sIMR 26.68+/-2.06, P<0.0001). However, when collateral supply was accounted for there was no difference observed (cIMR 16.96+/-1.78 versus nonculprit sIMR 18.37+/ 1.89, P=0.52; post percutaneous intervention sIMR 18.5+/-1.94 versus cIMR 16.96+/ 1.78, P=0.42). CONCLUSIONS: When collateral supply is accounted for, epicardial stenosis does not increase microvascular resistance in patients with stable angina. PMID- 22319069 TI - Clinical outcomes and treatment after drug-eluting stent failure: the absence of traditional risk factors for in-stent restenosis. AB - BACKGROUND: The optimal percutaneous treatment of drug-eluting stent (DES) in stent restenosis (ISR) and the correlates for recurrent DES ISR remain unclear. METHODS AND RESULTS: From 2003 to 2008, 563 patients presenting with recurrent symptoms of ischemia and angiographic ISR after DES implantation were included. Of these, 327 were treated with re-DES (58.1%), 132 underwent vascular brachytherapy (23.4%), and 104 were treated with conventional balloon angioplasty (18.5%). Variables associated with target lesion revascularization at 1 year were explored by individual proportional hazard models. This population presents a high prevalence of comorbidities, including diabetes (43.7%), previous myocardial infarction (MI) (45.8%), coronary bypass graft surgery (39.2%), chronic renal failure (18.8%), and heart failure (17.3%). Baseline clinical characteristics were balanced among the 3 groups; however, patients undergoing vascular brachytherapy presented with more complex lesions and a higher prevalence of prior stent/vascular brachytherapy failure than did the rest of the population. The overall incidence of recurrent DES failure at 1-year follow-up was 12.2%, which was similar among the 3 groups (P=0.41). The rate of the composite end point (death, Q-wave-MI and target lesion revascularization) at 1-year follow-up was 14.1% for re-DES, 17.5% for vascular brachytherapy, and 18.0% for conventional balloon angioplasty (P=0.57). After univariable analysis tested the traditional known covariates related to ISR, none of them were associated with repeat target lesion revascularization. CONCLUSIONS: Recurrence of ISR after DES treatment failure is neither infrequent nor benign, and optimal therapy remains unclear and challenging. Given the absence of traditional risk factors for ISR in this population, further research is required to elucidate both the correlates involved in DES ISR and the optimal treatment for this condition. PMID- 22319070 TI - Gaining confidence in cross-species annotation transfer: from simple molecular function to complex phenotypic traits. AB - Cross-species annotation transfer is a widely used approach for transferring information about simple molecular functions or pathways from one protein in one species to its ortholog in another species. In crop species, the phenotypic traits of interest, such as grain yield, are very complex and are often related to multiple biological processes and systems. It is still unclear to what extent the high level annotations describing phenotypic traits can also be reliably transferred across species. In this work, we have developed a procedure to measure precisely the transferability of these functional annotations from one species to another and demonstrate its application to Arabidopsis and several crop species. This comparative analysis is a step towards assigning higher level biological function to genes and gene networks as part of the wider genotype to phenotype challenge. PMID- 22319071 TI - Response to Open Peer Commentaries on "Neuroethics: A New Way of Doing Ethics" PMID- 22319072 TI - Type III secretion and effectors shape the survival and growth pattern of Pseudomonas syringae on leaf surfaces. AB - The bacterium Pseudomonas syringae pv syringae B728a (PsyB728a) uses a type III secretion system (T3SS) to inject effector proteins into plant cells, a process that modulates the susceptibility of different plants to infection. Analysis of GREEN FLUORESCENT PROTEIN-expressing PsyB728a after spray inoculation without additives under moderate relative humidity conditions permitted (1) a detailed analysis of this strain's survival and growth pattern on host (Nicotiana benthamiana) and nonhost (tomato [Solanum lycopersicum]) leaf surfaces, (2) an assessment of the role of plant defenses in affecting PsyB728a leaf surface (epiphytic) growth, and (3) the contribution of the T3SS and specific effectors to PsyB728a epiphytic survival and growth. On host leaf surfaces, PsyB728a cells initially persist without growing, and show an increased population only after 48 h, unless plants are pretreated with the defense-inducing chemical benzothiazole. During the persistence period, some PsyB728a cells induce a T3SS reporter, whereas a T3SS-deficient mutant shows reduced survival. By 72 h, rare invasion by PsyB728a to the mesophyll region of host leaves occurs, but endophytic and epiphytic bacterial growths are not correlated. The effectors HopZ3 and HopAA1 delay the onset of epiphytic growth of PsyB728a on N. benthamiana, whereas they promote epiphytic survival/growth on tomato. These effectors localize to distinct sites in plant cells and likely have different mechanisms of action. HopZ3 may enzymatically modify host targets, as it requires residues important for the catalytic activity of other proteins in its family of proteases. Thus, the T3SS, HopAA1, HopZ3, and plant defenses strongly influence epiphytic survival and/or growth of PsyB728a. PMID- 22319073 TI - Fission yeast HMT1 lowers seed cadmium through phytochelatin-dependent vacuolar sequestration in Arabidopsis. AB - Much of our dietary uptake of heavy metals is through the consumption of plants. A long-sought strategy to reduce chronic exposure to heavy metals is to develop plant varieties with reduced accumulation in edible tissues. Here, we describe that the fission yeast (Schizosaccharomyces pombe) phytochelatin (PC)-cadmium (Cd) transporter SpHMT1 produced in Arabidopsis (Arabidopsis thaliana) was localized to tonoplast, and enhanced tolerance to and accumulation of Cd2+, copper, arsenic, and zinc. The action of SpHMT1 requires PC substrates, and failed to confer Cd2+ tolerance and accumulation when glutathione and PC synthesis was blocked by L-buthionine sulfoximine, or only PC synthesis is blocked in the cad1-3 mutant, which is deficient in PC synthase. SpHMT1 expression enhanced vacuolar Cd2+ accumulation in wild-type Columbia-0, but not in cad1-3, where only approximately 35% of the Cd2+ in protoplasts was localized in vacuoles, in contrast to the near 100% found in wild-type vacuoles and approximately 25% in those of cad2-1 that synthesizes very low amounts of glutathione and PCs. Interestingly, constitutive SpHMT1 expression delayed root to-shoot metal transport, and root-targeted expression confirmed that roots can serve as a sink to reduce metal contents in shoots and seeds. These findings suggest that SpHMT1 function requires PCs in Arabidopsis, and it is feasible to promote food safety by engineering plants using SpHMT1 to decrease metal accumulation in edible tissues. PMID- 22319074 TI - A peroxidase-dependent apoplastic oxidative burst in cultured Arabidopsis cells functions in MAMP-elicited defense. AB - Perception by plants of so-called microbe-associated molecular patterns (MAMPs) such as bacterial flagellin, referred to as pattern-triggered immunity, triggers a rapid transient accumulation of reactive oxygen species (ROS). We previously identified two cell wall peroxidases, PRX33 and PRX34, involved in apoplastic hydrogen peroxide (H2O2) production in Arabidopsis (Arabidopsis thaliana). Here, we describe the generation of Arabidopsis tissue culture lines in which the expression of PRX33 and PRX34 is knocked down by antisense expression of a heterologous French bean (Phaseolus vulgaris) peroxidase cDNA construct. Using these tissue culture lines and two inhibitors of ROS generation, azide and diphenylene iodonium, we found that perxoxidases generate about half of the H2O2 that accumulated in response to MAMP treatment and that NADPH oxidases and other sources such as mitochondria account for the remainder of the ROS. Knockdown of PRX33/PRX34 resulted in decreased expression of several MAMP-elicited genes, including MYB51, CYP79B2, and CYP81F2. Similarly, proteomic analysis showed that knockdown of PRX33/PRX34 led to the depletion of various MAMP-elicited defense related proteins, including the two cysteine-rich peptides PDF2.2 and PDF2.3. Knockdown of PRX33/PRX34 also led to changes in the cell wall proteome, including increases in enzymes involved in cell wall remodeling, which may reflect enhanced cell wall expansion as a consequence of reduced H2O2-mediated cell wall cross linking. Comparative metabolite profiling of a CaCl2 extract of the PRX33/PRX34 knockdown lines showed significant changes in amino acids, aldehydes, and keto acids but not fatty acids and sugars. Overall, these data suggest that PRX33/PRX34-generated ROS production is involved in the orchestration of pattern triggered immunity in tissue culture cells. PMID- 22319075 TI - Identification of candidate genes underlying an iron efficiency quantitative trait locus in soybean. AB - Prevalent on calcareous soils in the United States and abroad, iron deficiency is among the most common and severe nutritional stresses in plants. In soybean (Glycine max) commercial plantings, the identification and use of iron-efficient genotypes has proven to be the best form of managing this soil-related plant stress. Previous studies conducted in soybean identified a significant iron efficiency quantitative trait locus (QTL) explaining more than 70% of the phenotypic variation for the trait. In this research, we identified candidate genes underlying this QTL through molecular breeding, mapping, and transcriptome sequencing. Introgression mapping was performed using two related near-isogenic lines in which a region located on soybean chromosome 3 required for iron efficiency was identified. The region corresponds to the previously reported iron efficiency QTL. The location was further confirmed through QTL mapping conducted in this study. Transcriptome sequencing and quantitative real-time-polymerase chain reaction identified two genes encoding transcription factors within the region that were significantly induced in soybean roots under iron stress. The two induced transcription factors were identified as homologs of the subgroup lb basic helix-loop-helix (bHLH) genes that are known to regulate the strategy I response in Arabidopsis (Arabidopsis thaliana). Resequencing of these differentially expressed genes unveiled a significant deletion within a predicted dimerization domain. We hypothesize that this deletion disrupts the Fe-DEFICIENCY INDUCED TRANSCRIPTION FACTOR (FIT)/bHLH heterodimer that has been shown to induce known iron acquisition genes. PMID- 22319076 TI - Supervision quartets. PMID- 22319077 TI - Do great local minds think alike? Comparing perceptions of the social determinants of health between non-profit and governmental actors in two Canadian cities. AB - Cities are important sites for intervention on social determinants of health (SDOH); yet, little is known about how influential local actors, namely workers in municipal governments (GOVs) and community-based organizations (CBOs), perceive the SDOH. Capturing and comparing perceptions between these groups are important for assessing how SDOH discourse has permeated local actors' thinking- a meaningful endeavour as local-level health equity action often invokes inter institutional partnerships. This paper compares SDOH perceptions between CBO workers in Hamilton, Ontario, with politicians and senior-level staff in GOVs in Vancouver, British Columbia, based on two studies with surveys containing identical questions on SDOH perceptions. Overall, there was high comparability between the groups in their relative ratings of the SDOH. Both groups assigned high levels of 'influence' and 'priority' to 'healthy lifestyles' and 'clean air and water' and lower levels to 'strong community' and 'income'. Given the importance of a shared vision in collaborative enterprises, the comparability of perceptions between the groups found here holds promise for the prospect of inter institutional partnerships. However, the low rating assigned to more structural health determinants suggests that more work is needed from researchers and advocates to effectively advance a health equity agenda at the local level in Canada. PMID- 22319078 TI - The sensitivity and specificity of pain diagrams in rheumatic disease referrals. AB - OBJECTIVES: To determine patterns on pain diagrams and corresponding diagnoses in patients referred to a rheumatology clinic and their sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively). METHODS: All new adult patient referrals from two rheumatologists over 6 years were reviewed and eligible if a pain diagram had been completed and they were not previously diagnosed with a rheumatic disease. Pain diagrams completed by the patient were organized into patterns based on the location of joint and/or soft tissue areas by two independent observers. RESULTS: A total of 1101 patients were included. Five major patterns evolved: soft tissue (widespread pain or regional pain such as an entire arm) (n = 236), symmetrical articular (n = 647), asymmetrical articular (n = 136), monoarticular (n = 35) and back (n = 46); 480 had inflammatory arthritis, of whom 121 had RA, 35 PsA, 46 SpAs and 63 crystal arthropathy. FM or chronic pain also occurred in 63 and 25 had PMR. The sensitivity, specificity, PPV and NPV for polyarticular symmetrical pattern in RA was 87.6, 44.7, 16.4 and 96.7% and for inflammatory arthritis with symmetrical or asymmetrical pattern was 82.3, 37.4, 50.4 and 73.2%; and a back pattern in AS was 10.9, 98.9, 41.7 and 96.2%. Inter-rater reliability was high for monoarticular, symmetrical and asymmetrical patterns (intra-class correlation coefficient >= 0.777). CONCLUSION: Pain diagram patterns may help to increase the likelihood of various rheumatic diagnoses including polyarticular pattern and inflammatory arthritis, and there was high inter-rater reliability. However, testing the value of pain diagrams in addition to a referral note is necessary to determine if they have added value. PMID- 22319079 TI - Stepping into the state of rheumatology in East Africa. PMID- 22319080 TI - Assessing early performance in the patient-doctor relationship in dental education. AB - In addition to current admissions criteria, the assessment of qualities related to humanistic medicine may help predict clinical and academic performance in dental education. The objective of this feasibility study was to develop and assess the reliability of a coding scheme to quantify and rate qualitative formative narratives describing individual student performance in a medical interview course that utilizes principles of humanistic medicine. A mixed method, using focus groups and individual interviews, was used to develop a coding strategy. Three coders retrospectively rated 209 formative narratives evaluating first-year students at the Harvard School of Dental Medicine to determine high and low performance in this course. Interrater reliability was tested. The focus groups yielded the use of superlatives to identify high performance, with their absence indicating low performance. This study found a high level of calibration among independent coders (Cronbach's alpha 0.75). Twenty-four (11.5 percent) of the narrative evaluations were coded as "high performers" and seven (3.3 percent) as "low performers." The results demonstrate the feasibility of quantifying narrative evaluations to determine high and low performance in a patient-centered course for dental students. It may be that humanistic qualities taught in a patient-centered medical interview course are more significant competencies than previously thought. PMID- 22319081 TI - Association between students' dental admission test scores and performance on comprehensive clinical exams. AB - This study examined the association between Dental Admission Test (DAT) scores and the comprehensive exams conducted at Harvard School of Dental Medicine. The authors hypothesized that students who scored high on the DAT would also perform well on the comprehensive examinations. Sixty-six students from the graduating classes of 2005 and 2006 were included. The outcome variable of interest was the final composite grade obtained by the students in the three comprehensive examinations. The main independent variable of interest was the individual component scores on the DAT. Multivariable logistic regression analysis using the maximum likelihood methods was used to examine the association between comprehensive exam grades and DAT scores. Effects of age, gender, and race/ethnicity were adjusted in the regression models. On the first comprehensive examination, seventeen students obtained an Honors grade, while thirteen did so on the second comprehensive examination and fifteen on the third comprehensive examination. None of the DAT component scores were significantly associated with Honors grades on the first comprehensive examination. On the second comprehensive examination, quantitative reasoning scores (OR=2.48, 95 percent CI=1.09-5.68, p=0.03) and total science scores (OR=14.17, 95 percent CI=1.89-106.80, p=0.01) were significantly associated with Honors grades. Reading comprehension score was associated with increased odds of obtaining Honors grade on the third comprehensive examination (OR=1.81, 95 percent CI=1.13-2.92, p=0.01). Students who scored well on the quantitative reasoning, total science, and reading comprehension sections of the DAT had higher odds of receiving an Honors grade on the second and third comprehensive examinations. These factors may be associated with the problem-solving/critical thinking components in the school's PBL curriculum. PMID- 22319082 TI - Can patients help teach professionalism and empathy to dental students? Adding patient videos to a lecture course. AB - A key aspect of predoctoral dental education involves ethics/professionalism and interpersonal communications. Empathy is an integral aspect of both. This study at the Schulich School of Medicine and Dentistry, University of Western Ontario, examined predoctoral students' perspectives to determine the impact of new educational methodologies designed to integrate patients' voices into a patient management lecture course. Videos of patients describing their dental experiences were added along with classroom discussion and students' reflective journals on the topics raised. Early results indicate that students perceived this innovation enhanced the teaching of professionalism, raised their awareness of the importance of empathy, and was a well-received addition to the course. PMID- 22319083 TI - Leadership training for oral health professionals: a call to action. AB - With dramatic changes in the scope and mode of delivering oral health care on the horizon, a strategic approach to addressing the emerging opportunities and challenges is required. Such an approach will demand new and sustained initiatives to develop leaders with the skills, knowledge, and passion to guide oral health care into the future. The purpose of this position paper is to define the need for leadership training programs for dental and dental hygiene students to become future leaders. Whether these oral health professionals become leaders within a solo or group practice or at the local or national level of their profession, they must be given the mindset and tools to lead. This position paper will describe goals for leadership training and give examples of some programs that currently exist in dental education and other professional settings as the background for a call to action for dental education to provide leadership training opportunities for its students. PMID- 22319084 TI - Program design considerations for leadership training for dental and dental hygiene students. AB - Since leadership is an essential part of the oral health professions, oral health educators can play an essential role in establishing a culture of leadership and in mentoring students to prepare them for future leadership roles within the profession. However, leadership training for oral health professionals is a relatively new concept and is frequently not found within dental and dental hygiene curricula. The purpose of this article is to propose several models for leadership training that are specific to the oral health professions. The authors hope that providing an overview of leadership programs in academic dental institutions will encourage all U.S. and Canadian dental schools to begin developing a culture that promotes leadership development. PMID- 22319085 TI - Mental health of postgraduate orthodontic students in India: a multi-institution survey. AB - The aim of this study was to evaluate the mental health of postgraduate orthodontic students in India by assessing the extent of three common negative affective states: depression, anxiety, and stress. Three hundred and thirty postgraduate students from thirty-two dental colleges across India anonymously completed the short version of the Depression Anxiety Stress Scale (DASS21). The statistical analysis included summary statistics, nonparametric tests for intergroup comparisons, and logistic regressions to evaluate the influence of age, gender, year of study, and marital status on these mental states. In comparison to the general population, the students experienced mildly elevated levels of depression and anxiety (11+/-5.1 and 8.2+/-4.1, respectively) and a moderately elevated level of psychological stress (22+/-5.2). A moderate or higher level of coexisting symptoms of all three affective states was seen in 15.8 percent of the students. Female students reported a higher level of depression than males and were two and half times more likely to experience depression to a moderate or higher level. First-year students exhibited lower levels in all three states than those in the second and third years and had lower odds than third-year students of developing a moderate or higher level of any of the three affective states. Marriage had a significant buffering potential against all these states. The results clearly indicate a suboptimal level of mental health in these postgraduate students of the specialty and the need to improve their mental resilience and the academic climate. PMID- 22319086 TI - Dental students' regard for patients from often-stigmatized populations: findings from an Indian dental school. AB - The aim of this study was to evaluate and compare a group of Indian dental students' attitudes toward HIV-positive status, substance misuse, intellectual disability, acute mental illness, and lesbian, gay, bisexual, transgender (LGBT) orientation. Two hundred and twelve students at various stages in the dental curriculum anonymously completed the Medical Condition Regard Scale (MCRS) for these conditions. Friedman and Kruskal-Wallis tests were used, respectively, to analyze the intrastage and interstage differences in MCRS scores. The results revealed that the regard of dental students was considerably positive for all the conditions except LGBT, for which it was just borderline positive. Intellectual disability received the highest regard among all the conditions and LGBT the least. An intermediary and comparable regard was noted for acute mental illness and HIV-positive status followed by substance misuse. While the regard for LGBT remained consistent throughout the curriculum, those for other conditions showed a marginal decrease at the completion of the clinical training. Active curricular reforms are required to ensure a more inclusive and nondiscriminatory dental care environment for patients from such often-stigmatized populations, especially those with LGBT orientation and substance misuse. PMID- 22319093 TI - Selective bird predation on the peppered moth: the last experiment of Michael Majerus. AB - Colour variation in the peppered moth Biston betularia was long accepted to be under strong natural selection. Melanics were believed to be fitter than pale morphs because of lower predation at daytime resting sites on dark, sooty bark. Melanics became common during the industrial revolution, but since 1970 there has been a rapid reversal, assumed to have been caused by predators selecting against melanics resting on today's less sooty bark. Recently, these classical explanations of melanism were attacked, and there has been general scepticism about birds as selective agents. Experiments and observations were accordingly carried out by Michael Majerus to address perceived weaknesses of earlier work. Unfortunately, he did not live to publish the results, which are analysed and presented here by the authors. Majerus released 4864 moths in his six-year experiment, the largest ever attempted for any similar study. There was strong differential bird predation against melanic peppered moths. Daily selection against melanics (s ~ 0.1) was sufficient in magnitude and direction to explain the recent rapid decline of melanism in post-industrial Britain. These data provide the most direct evidence yet to implicate camouflage and bird predation as the overriding explanation for the rise and fall of melanism in moths. PMID- 22319094 TI - Primate communication in the pure ultrasound. AB - Few mammals-cetaceans, domestic cats and select bats and rodents-can send and receive vocal signals contained within the ultrasonic domain, or pure ultrasound (greater than 20 kHz). Here, we use the auditory brainstem response (ABR) method to demonstrate that a species of nocturnal primate, the Philippine tarsier (Tarsius syrichta), has a high-frequency limit of auditory sensitivity of ca 91 kHz. We also recorded a vocalization with a dominant frequency of 70 kHz. Such values are among the highest recorded for any terrestrial mammal, and a relatively extreme example of ultrasonic communication. For Philippine tarsiers, ultrasonic vocalizations might represent a private channel of communication that subverts detection by predators, prey and competitors, enhances energetic efficiency, or improves detection against low-frequency background noise. PMID- 22319095 TI - Plant radiation history affects community assembly: evidence from the New Zealand alpine. AB - The hypothesis that early plant radiations on islands dampen diversification and reduce habitat occupancy of later radiations via niche pre-emption has never, to our knowledge, been tested. We investigated clade-level dynamics in plant radiations in the alpine zone, New Zealand. Our aim was to determine whether radiations from older colonizations influenced diversification and community dominance of species from later colonizations within a common bioclimatic zone over the past ca 10 Myr. We used stem ages derived from the phylogenies of 17 genera represented in alpine plant communities in the Murchison Mountains, Fiordland, and assessed their presence and cover in 262 (5 * 5 m) vegetation plots. Our results show clear age-related community assembly effects, whereby congenerics from older colonizing genera co-occur more frequently and with greater cover per unit area than those from younger colonizing genera. However, we find no evidence of increased species richness with age of colonization in the alpine zone. The data support priority effects via niche pre-emption among plant radiations influencing community assembly. PMID- 22319096 TI - Delayed song maturation and territorial aggression in a songbird. AB - Asymmetries in competitive ability can determine the outcome of social interactions in animals and are often expressed through differences in sexual traits. Competitive ability (resource holding potential, RHP), trait expression and ultimately reproductive success may vary with an individual's age or experience. In some species, reproductively mature males delay acquisition of some adult traits and thereby signal their young age. Theory on animal contests predicts that individuals assess the RHP of an opponent relative to their own, such that escalation is more common between evenly matched opponents. Here, we test predictions from this hypothesis that males respond to a territorial intruder based on their RHP relative to the intruder's RHP. We simulated white crowned sparrows (Zonotrichia leucophrys) intruding into the territory of a recruit or return. Playback of a song repertoire simulating a young male (recruit) elicited a weaker response from established territory holders (return), but a stronger response from recruits. Playback of a single song type simulating an older male elicited the opposite responses. This indicates that males distinguished between simulated young and old intruders based on song, and responded differently depending on their own experience. Our study highlights the possibility that receiver as well as sender traits should be considered when interpreting animal interactions. PMID- 22319097 TI - Discordant patterns of nuclear and mitochondrial introgression in Iberian populations of the European common frog (Rana temporaria). AB - Amphibians often show complex histories of intraspecific and interspecific genetic introgression, which might differ in mitochondrial and nuclear genes. In our study of the genetic differentiation of the European common frog, Rana temporaria (159 specimens from 23 populations were analyzed for 24 presumptive allozyme loci; 82 specimens were sequenced for a 540-bp fragment of the mitochondrial 16S rRNA gene), multilocus correspondence analysis (CA) and Bayesian assignment tests of the nuclear data were concordant in identifying 2 population groups corresponding to 1) the Pyrenees in the east and 2) the Galicia and Asturias regions in the west, the latter corresponding to the subspecies R. temporaria parvipalmata. Geographically intermediate populations were genetically intermediate in the allozyme CA and, less clearly in the Bayesian assignment, with mitochondrial haplotypes exclusively belonging to the parvipalmata group. This indicates different degrees of introgression in the mitochondrial and nuclear genomes. Although Pyrenean high-altitude populations are morphologically distinct from low-altitude populations, these 2 groups were not separate clusters in any analysis. This suggests that the morphological differences may be due to fast adaptation to elevational gradients, likely under maintenance of gene flow, and that the underlying genetic changes are not detectable by the analyzed markers. We argue that a parsimonious explanation for the observed pattern along the east-west axis in northern Spain may be competition between invading and resident populations, with no need to invoke selection. However, in order to conclusively rule out selective processes, additional and finer scale data are required to test for asymmetric mating preference/behaviour, sex-biased gene flow, or sex-biased survival of potential hybrids. PMID- 22319098 TI - Genetic population substructure in bison at Yellowstone National Park. AB - The Yellowstone National Park bison herd is 1 of only 2 populations known to have continually persisted on their current landscape since pre-Columbian times. Over the last century, the census size of this herd has fluctuated from around 100 individuals to over 3000 animals. Previous studies involving radiotelemetry, tooth wear, and parturition timing provide evidence of at least 2 distinct groups of bison within Yellowstone National Park. To better understand the biology of Yellowstone bison, we investigated the potential for limited gene flow across this population using multilocus Bayesian clustering analysis. Two genetically distinct and clearly defined subpopulations were identified based on both genotypic diversity and allelic distributions. Genetic cluster assignments were highly correlated with sampling locations for a subgroup of live capture individuals. Furthermore, a comparison of the cluster assignments to the 2 principle winter cull sites revealed critical differences in migration patterns across years. The 2 Yellowstone subpopulations display levels of differentiation that are only slightly less than that between populations which have been geographically and reproductively isolated for over 40 years. The identification of cryptic population subdivision and genetic differentiation of this magnitude highlights the importance of this biological phenomenon in the management of wildlife species. PMID- 22319099 TI - Awareness and behavior of oncologists and support measures in medical institutions related to ongoing employment of cancer patients in Japan. AB - OBJECTIVE: Improved outcomes of cancer treatment allow patients to undergo treatment while working. However, support from oncologists and medical institutions is essential for patients to continue working. This study aimed to clarify oncologists' awareness and behavior regarding patients who work during treatment, support in medical institutions and their association. METHODS: A questionnaire was mailed to all 453 diplomates and faculty of the subspecialty board of medical oncology in the Japanese Society of Medical Oncology and all 1016 surgeons certified by the Japanese Board of Cancer Therapy living in the Kanto area. The questionnaire assessed demographics, oncologist awareness and behavior regarding patient employment and support measures at their medical institutions. Logistic regression analysis was used to examine the association of awareness and behavior of oncologists with support measures at their institutions. RESULTS: A total of 668 individuals participated. The overall response rate was 45.5%. Only 53.6% of respondents advised patients to tell their supervisors about prospects for treatment and ask for understanding. For medical institutions, 28.8% had a nurse-involved counseling program and adjustments in radiation therapy (28.0%) and chemotherapy (41.9%) schedules to accommodate patients' work. There was a significant correlation between awareness and behavior of oncologists and medical institutions' measures to support employed cancer patients. CONCLUSIONS: There is room for improvement in awareness and behavior of oncologists and support in medical institutions for cancer patients continuing to work. Oncologists could support working patients by exerting influence on their medical institutions. Conversely, proactive development of support measures by medical institutions could alter the awareness and behavior of oncologists. PMID- 22319101 TI - The benefits of planar circular mouths on suction feeding performance. AB - Suction feeding is the most common form of prey capture across aquatic feeding vertebrates and many adaptations that enhance efficiency and performance are expected. Many suction feeders have mechanisms that allow the mouth to form a planar and near-circular opening that is believed to have beneficial hydrodynamic effects. We explore the effects of the flattened and circular mouth opening through computational fluid dynamics simulations that allow comparisons with other mouth profiles. Compared to mouths with lateral notches, we find that the planar mouth opening results in higher flow rates into the mouth and a region of highest flow that is positioned at the centre of the mouth aperture. Planar mouths provide not only for better total fluid flow rates through the mouth but also through the centre of the mouth near where suction feeders position their prey. Circular mouths are shown to provide the quickest capture times for spherical and elliptical prey because they expose the prey item to a large region of high flow. Planar and circular mouths result in higher flow velocities with peak flow located at the centre of the mouth opening and they maximize the capacity of the suction feeders to exert hydrodynamic forces on the prey. PMID- 22319100 TI - Two decades of studying non-covalent biomolecular assemblies by means of electrospray ionization mass spectrometry. AB - Mass spectrometry (MS) is a recognized approach for characterizing proteins and the complexes they assemble into. This application of a long-established physico chemical tool to the frontiers of structural biology has stemmed from experiments performed in the early 1990s. While initial studies focused on the elucidation of stoichiometry by means of simple mass determination, developments in MS technology and methodology now allow researchers to address questions of shape, inter-subunit connectivity and protein dynamics. Here, we chart the remarkable rise of MS and its application to biomolecular complexes over the last two decades. PMID- 22319102 TI - Glial progenitor cell recruitment drives aggressive glioma growth: mathematical and experimental modelling. AB - Currently available glioma treatments remain unsuccessful at prolonging disease free remission. Recent evidence suggests that tumour recruitment of glial progenitor cells by platelet-derived growth factor (PDGF) may play a role in the development and progression of these tumours. Building upon our recent experimental results and previous proliferation-invasion (PI) reaction-diffusion model, in this study, we created a proliferation-invasion-recruitment (PIR) model that includes a mechanism for progenitor cell recruitment, wherein paracrine PDGF signalling stimulates migration and proliferation of progenitors derived from the local brain environment. Parametrizing this mathematical model with data obtained from the PDGF-driven rat glioma model, we explored the consequences of recruitment, using the PIR model to compare the effects of high versus low PDGF secretion rates on tumour growth and invasion dynamics. The mathematical model predicts correlation between high levels of recruitment and both increased radial velocity of expansion on magnetic resonance imaging and less diffusely invasive edges. Thus, the PIR model predicts that PDGF levels correlate with tumour aggressiveness, and results are consistent with both human and experimental data, demonstrating that the effects of progenitor cell recruitment provide a novel mechanism to explain the variability in the rates of proliferation and dispersion observed in human gliomas. PMID- 22319103 TI - Capture of cell-derived microvesicles (exosomes and apoptotic bodies) by human plasmacytoid dendritic cells. AB - cDCs and pDCs differ in multiple aspects. Among those, antigen capture is a recognized feature of cDCs, whereas pDCs display poor capacity to capture cell derived antigens. However, animal models of organ transplantation suggested a role for pDCs in tolerance induction via phagocytosis of donor antigens. In a transplantation setting, microvesicles, such as apoptotic bodies and exosomes secreted by the graft, may be potential sources of alloantigen. Here, we tested the capacity of human pDCs to capture exosomes and apoptotic bodies from Jurkat T cells. Exosomes and apoptotic bodies were indeed captured by pDCs, although required longer times of incubation when compared with the highly endocytic cDCs. In cDCs and pDCs, exosome capture was more efficient than apoptotic bodies. Endocytosis inhibitors clearly impaired exosome capture by cDCs, although this could not be verified in pDCs as a result of cellular toxicity. Functionally, capture of Jurkat-derived exosomes did not induce nor prevent pDC maturation, and exosome-loaded pDCs induced T cell proliferation, suggesting a link between capture and presentation. Thus, exosomes and apoptotic bodies may be sources of antigen for human pDCs. PMID- 22319104 TI - CD66b overexpression and homotypic aggregation of human peripheral blood neutrophils after activation by a gram-positive stimulus. AB - Neutrophils represent the main component of innate immunity in the clearance of bacterial infections. To pass the tissue and to localize and reach the site of infection, the peripheral blood neutrophils have to pass through a complex receptor-mediated interaction with the endothelial layer. Under pathophysiological conditions, such as severe sepsis, this process is impaired and often characterized by neutrophil aggregation. In this study, we examined the impact of three different Staphylococcus aureus strains on the activation status of human peripheral blood neutrophils by coincubation of bacterial culture supernatant with whole blood. This complex interaction of a gram-positive stimulus with blood components leads to a special neutrophil activation phenotype, which is characterized by an overexpression of the cell-surface molecule CD66b. The process is accompanied by a strong increase of homotypic aggregates and seems to be initialized by a massive activation impulse caused by the interplay of plasma components. This maximum activation of neutrophils prior to the complex and highly regulated activation required for transmigration might play a key role in the neutrophil dysfunction in gram-positive sepsis. PMID- 22319105 TI - Admission international normalized ratio levels, early treatment strategies, and major bleeding risk among non-ST-segment-elevation myocardial infarction patients on home warfarin therapy: insights from the National Cardiovascular Data Registry. AB - BACKGROUND: Non-ST-segment-elevation myocardial infarction patients on home warfarin pose treatment concerns because of their potential increased risk of bleeding. Expert opinion from the American College of Cardiology/American Heart Association guidelines suggest holding anticoagulants and initiating antiplatelet therapy among therapeutically anticoagulated non-ST-segment-elevation myocardial infarction patients. Yet, little is known about contemporary treatment patterns and bleeding risks in this population. METHODS AND RESULTS: We stratified 5787 non-ST-segment-elevation myocardial infarction patients on home warfarin therapy using data from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines by admission international normalized ratio (INR) levels: subtherapeutic (INR <2), therapeutic (INR, 2-3), and supratherapeutic (INR >3). Multivariable logistic generalized estimating equations models were constructed to examine the associations between admission INR level, early antithrombotic treatment and invasive therapy, and risk of in-hospital major bleeding. Among these patients, 46%, 35%, and 19% had subtherapeutic, therapeutic, and supratherapeutic admission INR levels, respectively. Risk of major bleeding was higher among patients with therapeutic (15%; adjusted odds ratio, 1.25; 95% confidence interval [CI], 1.03 1.50) and supratherapeutic (22%; odds ratio, 1.60; 95% CI, 1.30-1.97) anticoagulation compared with the subtherapeutic group (12%). Among patients with admission INR >=2, 45% were treated with early (within 24 hours) heparin, 35% with early clopidogrel, 14% with early glycoprotein IIb/IIIa inhibitor, and 36% with early invasive strategy. Early antithrombotic treatment was associated with increased bleeding risk (odds ratio, 1.40 [95% CI, 1.14-1.72] for heparin; 1.50 [95% CI, 1.22-1.84] for clopidogrel; and 1.82 [95% CI, 1.43-2.32] for glycoprotein IIb/IIIa inhibitor); however, an early invasive strategy was not (odds ratio, 1.09; 95% CI, 0.86-1.37). No significant interactions were observed between INR level and use of each early treatment in its association with bleeding. CONCLUSIONS: National patterns of early antithrombotic treatment for non-ST-segment-elevation myocardial infarction patients on home warfarin diverge from expert opinion provided by current practice guidelines. Early antithrombotic treatment was associated with increased bleeding risk regardless of admission INR level. PMID- 22319106 TI - Long-term effects of sildenafil in a rat model of chronic mitral regurgitation: benefits of ventricular remodeling and exercise capacity. AB - BACKGROUND: We tested the hypothesis that chronic treatment with sildenafil attenuates left ventricular (LV) remodeling and prevents exercise intolerance in chronic mitral regurgitation (MR). METHODS AND RESULTS: MR was created in Sprague Dawley rats by making a hole on the mitral leaflet. Two weeks after MR creation, MR and LV dilatation were confirmed by echocardiography, and rats were randomly assigned to sildenafil treatment (MR+sildenafil group; 50 mg/kg PO twice a day; n=16) or normal saline only (MR group; n=16) and continued for 4 months. Sixteen sham rats were compared with MR rats. After 4 months, LV size was smaller in the MR+sildenafil compared with the MR group (LV end-systolic dimension, 4.7+/-0.3 for sham versus 5.9+/-0.3 for MR+sildenafil versus 7.4+/-0.5 mm for MR; P<0.05; LV end-diastolic dimension, 8.3+/-0.4 versus 10.5+/-0.2 versus 11.7+/-0.61 mm, respectively; P<0.05). LV ejection fraction was greater in the MR+sildenafil group than in the MR group (70.2+/-2.2 for sham versus 67.0+/-4.2 for MR+sildenafil versus 58.9+/-2.5 for MR; P=0.01). Serial treadmill test revealed that exercise capacity was reduced in the MR but not in the MR+sildenafil group. Transcriptional profiling of cardiac apical tissues revealed that gene sets related to inflammatory response, DNA damage response, cell cycle checkpoint, and cellular signaling pathways were significantly enriched by genes with reciprocal changes. Pathological analysis showed that perivascular fibrosis was more prominent in the MR than in the MR+sildenafil group and that the percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells was 2-fold greater in the MR compared with the MR+sildenafil group. CONCLUSIONS: Sildenafil significantly attenuates LV remodeling and prevents exercise intolerance in a rat model of chronic MR. This benefit may be associated with the antiapoptotic, anti-inflammatory effects of sildenafil. PMID- 22319107 TI - Is inhibition of phosphodiesterase type 5 by sildenafil a promising therapy for volume-overload heart failure? PMID- 22319108 TI - The uremic myocardium and ischemic tolerance: a world of difference. PMID- 22319109 TI - Ischemic conditioning protects the uremic heart in a rodent model of myocardial infarction. AB - BACKGROUND: Outcomes after acute myocardial infarction in patients with chronic kidney disease are extremely poor. Ischemic conditioning techniques are among the most powerful cytoprotective strategies discovered to date. However, experimental data suggest that comorbidity may attenuate the protective effects of ischemic conditioning. METHODS AND RESULTS: We conducted investigations into the effects of chronic uremia on myocardial infarct size and the protective effects of ischemic preconditioning (IPC), remote ischemic preconditioning, and ischemic postconditioning in 2 rodent models of chronic uremia. In addition, a limited investigation into the signaling mechanisms involved in cardioprotection after IPC was performed in both uremic and nonuremic animals. Myocardial infarct size was increased in uremic animals, but all 3 conditioning strategies (IPC, remote IPC, ischemic postconditioning) proved highly efficacious in reducing myocardial infarct size (relative reduction, 86%, 39%, and 65% [P<0.005, P<0.05, and P<0.05], respectively). Moreover, some protocols (IPC and ischemic postconditioning) appeared to be more effective in uremic than in sham (nonuremic) animals. Analysis of the signaling mechanisms revealed that components of both the reperfusion injury salvage kinase and survivor activating factor enhancement pathways were similarly upregulated in both uremic and nonuremic animals after an IPC stimulus. CONCLUSION: Conditioning strategies may present the best opportunity to improve outcomes for patients with chronic kidney disease after an acute coronary syndrome. PMID- 22319110 TI - Experiments and theory of undulatory locomotion in a simple structured medium. AB - Undulatory locomotion of micro-organisms through geometrically complex, fluidic environments is ubiquitous in nature and requires the organism to negotiate both hydrodynamic effects and geometrical constraints. To understand locomotion through such media, we experimentally investigate swimming of the nematode Caenorhabditis elegans through fluid-filled arrays of micro-pillars and conduct numerical simulations based on a mechanical model of the worm that incorporates hydrodynamic and contact interactions with the lattice. We show that the nematode's path, speed and gait are significantly altered by the presence of the obstacles and depend strongly on lattice spacing. These changes and their dependence on lattice spacing are captured, both qualitatively and quantitatively, by our purely mechanical model. Using the model, we demonstrate that purely mechanical interactions between the swimmer and obstacles can produce complex trajectories, gait changes and velocity fluctuations, yielding some of the life-like dynamics exhibited by the real nematode. Our results show that mechanics, rather than biological sensing and behaviour, can explain some of the observed changes in the worm's locomotory dynamics. PMID- 22319111 TI - Lost at sea: genetic, oceanographic and meteorological evidence for storm-forced dispersal. AB - For many species, there is broad-scale dispersal of juvenile stages and/or long distance migration of individuals and hence the processes that drive these various wide-ranging movements have important life-history consequences. Sea turtles are one of these paradigmatic long-distance travellers, with hatchlings thought to be dispersed by ocean currents and adults often shuttling between distant breeding and foraging grounds. Here, we use multi-disciplinary oceanographic, atmospheric and genetic mixed stock analyses to show that juvenile turtles are encountered 'downstream' at sites predicted by currents. However, in some cases, unusual occurrences of juveniles are more readily explained by storm events and we show that juvenile turtles may be displaced thousands of kilometres from their expected dispersal based on prevailing ocean currents. As such, storms may be a route by which unexpected areas are encountered by juveniles which may in turn shape adult migrations. Increased stormy weather predicted under climate change scenarios suggests an increasing role of storms in dispersal of sea turtles and other marine groups with life-stages near the ocean surface. PMID- 22319112 TI - A composite computational model of liver glucose homeostasis. II. Exploring system behaviour. AB - Using a composite model of the glucose homeostasis system, consisting of seven interconnected submodels, we enumerate the possible behaviours of the model in response to variation of liver insulin sensitivity and dietary glucose variability. The model can reproduce published experimental manipulations of the glucose homeostasis system and clearly illustrates several important properties of glucose homeostasis-boundedness in model parameters of the region of efficient homeostasis, existence of an insulin sensitivity that allows effective homeostatic control and the importance of transient and oscillatory behaviour in characterizing homeostatic failure. Bifurcation analysis shows that the appearance of a stable limit cycle can be identified. PMID- 22319113 TI - High-resolution microrheology in the pericellular matrix of prostate cancer cells. AB - Many cells express a membrane-coupled external mechanical layer, the pericellular matrix (PCM), which often contains long-chain polymers. Its role and properties are not entirely known, but its functions are believed to include physical protection, mechanosensing, chemical signalling or lubrication. The viscoelastic response of the PCM, with polysaccharides as the main structural components, is therefore crucial for the understanding of its function. We have here applied microrheology, based on optically trapped micrometre-sized colloids, to the PCM of cultured PC3 prostate cancer cells. This technology allowed us to measure the extremely soft response of the PCM, with approximately 1 um height resolution. Exogenously added aggrecan, a hyaluronan-binding proteoglycan, caused a remarkable increase in thickness of the viscoelastic layer and also triggered filopodia-like protrusions. The viscoelastic response of the PCM, however, did not change significantly. PMID- 22319114 TI - The well-tuned blues: the role of structural colours as optical signals in the species recognition of a local butterfly fauna (Lepidoptera: Lycaenidae: Polyommatinae). AB - The photonic nanoarchitectures responsible for the blue colour of the males of nine polyommatine butterfly species living in the same site were investigated structurally by electron microscopy and spectrally by reflectance spectroscopy. Optical characterization was carried out on 110 exemplars. The structural data extracted by dedicated software and the spectral data extracted by standard software were inputted into an artificial neural network software to test the specificity of the structural and optical characteristics. It was found that both the structural and the spectral data allow species identification with an accuracy better than 90 per cent. The reflectance data were further analysed using a colour representation diagram built in a manner analogous to that of the human Commission Internationale de l'Eclairage diagram, but the additional blue visual pigment of lycaenid butterflies was taken into account. It was found that this butterfly-specific colour representation diagram yielded a much clearer distinction of the position of the investigated species compared with previous calculations using the human colour space. The specific colours of the investigated species were correlated with the 285 flight-period data points extracted from museum collections. The species with somewhat similar colours fly in distinct periods of the year such that the blue colours are well tuned for safe mate/competitor recognition. This allows for the creation of an effective pre-zygotic isolation mechanism for closely related synchronic and syntopic species. PMID- 22319115 TI - Broiler chickens can benefit from machine learning: support vector machine analysis of observational epidemiological data. AB - Machine-learning algorithms pervade our daily lives. In epidemiology, supervised machine learning has the potential for classification, diagnosis and risk factor identification. Here, we report the use of support vector machine learning to identify the features associated with hock burn on commercial broiler farms, using routinely collected farm management data. These data lend themselves to analysis using machine-learning techniques. Hock burn, dermatitis of the skin over the hock, is an important indicator of broiler health and welfare. Remarkably, this classifier can predict the occurrence of high hock burn prevalence with accuracy of 0.78 on unseen data, as measured by the area under the receiver operating characteristic curve. We also compare the results with those obtained by standard multi-variable logistic regression and suggest that this technique provides new insights into the data. This novel application of a machine-learning algorithm, embedded in poultry management systems could offer significant improvements in broiler health and welfare worldwide. PMID- 22319121 TI - The penetrance of an epigenetic trait in mice is progressively yet reversibly increased by selection and environment. AB - Natural selection acts on variation that is typically assumed to be genetic in origin. But epigenetic mechanisms, which are interposed between the genome and its environment, can create diversity independently of genetic variation. Epigenetic states can respond to environmental cues, and can be heritable, thus providing a means by which environmentally responsive phenotypes might be selectable independent of genotype. Here, we have tested the possibility that environment and selection can act together to increase the penetrance of an epigenetically determined phenotype. We used isogenic A(vy) mice, in which the epigenetic state of the A(vy) allele is sensitive to dietary methyl donors. By combining methyl donor supplementation with selection for a silent A(vy) allele, we progressively increased the prevalence of the associated phenotype in the population over five generations. After withdrawal of the dietary supplement, the shift persisted for one generation but was lost in subsequent generations. Our data provide the first demonstration that selection for a purely epigenetic trait can result in cumulative germline effects in mammals. These results present an alternative to the paradigm that natural selection acts only on genetic variation, and suggest that epigenetic changes could underlie rapid adaptation of species in response to natural environmental fluctuations. PMID- 22319122 TI - Multiple losses of flight and recent speciation in steamer ducks. AB - Steamer ducks (Tachyeres) comprise four species, three of which are flightless. The flightless species are believed to have diverged from a flying common ancestor during the Late Pleistocene; however, their taxonomy remains contentious. Of particular interest is the previously unstudied population of flying steamer ducks in the Falkland Islands. We present the first genetic data from this insular population, and illustrate that the flying and flightless steamer ducks on the Falkland Islands are genetically indistinguishable, in contrast to their traditional classification as separate species. The three species that reside in continental South America form a genetically distinct lineage from the Falkland Island ducks. The Falkland steamer ducks diverged from their continental relatives 2.2-0.6 million years ago, coincident with a probable land bridge connecting the Falkland Islands to the mainland. The three continental species share a common ancestor approximately 15 000 years ago, possibly owing to isolation during a recent glacial advance. The continental steamer duck species are not reciprocally monophyletic, but show some amount of genetic differentiation between them. Each lineage of Tachyeres represents a different stage between flight and flightlessness. Their phylogenetic relationships suggest multiple losses of flight and/or long-term persistence of mixed-flight capability. As such, steamer ducks may provide a model system to study the evolution of flightlessness. PMID- 22319123 TI - Multilocus genetic analyses differentiate between widespread and spatially restricted cryptic species in a model ascidian. AB - Elucidating the factors that shape species distributions has long been a fundamental goal in ecology and evolutionary biology. In spite of significant theoretical advancements, empirical studies of range limits have lagged behind. Specifically, little is known about how the attributes that allow species to expand their ranges and become widespread vary across phylogenies. Here, we studied the ascidian Botryllus schlosseri, a worldwide invasive species that is also characterized by marked genetic subdivision. Our study includes phylogenetic and population genetic data based on mitochondrial and nuclear genes, as well as polymorphic microsatellites for B. schlosseri colonies sampled from the southern and northern coasts of Europe and the eastern and western coasts of North America. We demonstrate that this well-known model organism comprises three highly divergent and probably reproductively isolated cryptic species (A, D and E), with two more (B and C) being suggested by data retrieved from GenBank. Among these, species A, recovered in all of the surveyed regions, is by far the most common and widespread. By contrast, species B-E, occurring mostly in sites from northern Europe, are considerably more geographically restricted. These findings, along with inferences made on transport opportunity, suggest that divergent evolutionary histories promoted differences in invasive potential between B. schlosseri sibling species, indicating that attributes that facilitate dramatic shifts in range limits can evolve more easily and frequently than previously thought. We propose environmental disturbance as a selective force that could have shaped the evolution of invasiveness in the B. schlosseri complex. PMID- 22319124 TI - To feed or to breed: morphological constraints of mouthbrooding in coral reef cardinalfishes. AB - Functionally coupled biomechanical systems are widespread in nature and are viewed as major constraints on evolutionary diversification, yet there have been few attempts to explore the implications of performing multiple functions within a single anatomical structure. Paternally mouthbrooding cardinalfishes present an ideal system to investigate the constraints of functional coupling as the oral jaws of male fishes are directly responsible for both feeding and reproductive functions. To test the effects of (i) mouthbrooding on feeding and (ii) feeding on reproductive potential we compared the feeding apparatus between sexes of nine species of cardinalfish and compared brood characteristics among species from different trophic groups, respectively. Mouthbrooding was strongly associated with the morphology of the feeding apparatus in males. Male cardinalfishes possessed longer heads, snouts and jaws than female conspecifics irrespective of body size, trophic group or evolutionary history. Conversely, reproductive potential also appeared to be related to trophic morphology. Piscivorous cardinalfishes produced larger, but fewer eggs, and had smaller brood volumes than species from the two invertebrate feeding groups. These interrelationships suggest that feeding and reproduction in the mouth of cardinalfishes may be tightly coupled. If so this may, in part, have contributed to the limited morphological diversification exhibited by cardinalfishes. PMID- 22319125 TI - Distinguishing geology from biology in the Ediacaran Doushantuo biota relaxes constraints on the timing of the origin of bilaterians. AB - The Ediacaran Doushantuo biota has yielded fossils that include the oldest widely accepted record of the animal evolutionary lineage, as well as specimens with alleged bilaterian affinity. However, these systematic interpretations are contingent on the presence of key biological structures that have been reinterpreted by some workers as artefacts of diagenetic mineralization. On the basis of chemistry and crystallographic fabric, we characterize and discriminate phases of mineralization that reflect: (i) replication of original biological structure, and (ii) void-filling diagenetic mineralization. The results indicate that all fossils from the Doushantuo assemblage preserve a complex melange of mineral phases, even where subcellular anatomy appears to be preserved. The findings allow these phases to be distinguished in more controversial fossils, facilitating a critical re-evaluation of the Doushantuo fossil assemblage and its implications as an archive of Ediacaran animal diversity. We find that putative subcellular structures exhibit fabrics consistent with preservation of original morphology. Cells in later developmental stages are not in original configuration and are therefore uninformative concerning gastrulation. Key structures used to identify Doushantuo bilaterians can be dismissed as late diagenetic artefacts. Therefore, when diagenetic mineralization is considered, there is no convincing evidence for bilaterians in the Doushantuo assemblage. PMID- 22319126 TI - Why are there so few fish in the sea? AB - The most dramatic gradient in global biodiversity is between marine and terrestrial environments. Terrestrial environments contain approximately 75-85% of all estimated species, but occupy only 30 per cent of the Earth's surface (and only approx. 1-10% by volume), whereas marine environments occupy a larger area and volume, but have a smaller fraction of Earth's estimated diversity. Many hypotheses have been proposed to explain this disparity, but there have been few large-scale quantitative tests. Here, we analyse patterns of diversity in actinopterygian (ray-finned) fishes, the most species-rich clade of marine vertebrates, containing 96 per cent of fish species. Despite the much greater area and productivity of marine environments, actinopterygian richness is similar in freshwater and marine habitats (15 150 versus 14 740 species). Net diversification rates (speciation-extinction) are similar in predominantly freshwater and saltwater clades. Both habitats are dominated by two hyperdiverse but relatively recent clades (Ostariophysi and Percomorpha). Remarkably, trait reconstructions (for both living and fossil taxa) suggest that all extant marine actinopterygians were derived from a freshwater ancestor, indicating a role for ancient extinction in explaining low marine richness. Finally, by analysing an entirely aquatic group, we are able to better sort among potential hypotheses for explaining the paradoxically low diversity of marine environments. PMID- 22319127 TI - Floral to green: mating switches moth olfactory coding and preference. AB - Mating induces profound physiological changes in a wide range of insects, leading to behavioural adjustments to match the internal state of the animal. Here, we show for the first time, to our knowledge, that a noctuid moth switches its olfactory response from food to egg-laying cues following mating. Unmated females of the cotton leafworm (Spodoptera littoralis) are strongly attracted to lilac flowers (Syringa vulgaris). After mating, attraction to floral odour is abolished and the females fly instead to green-leaf odour of the larval host plant cotton, Gossypium hirsutum. This behavioural switch is owing to a marked change in the olfactory representation of floral and green odours in the primary olfactory centre, the antennal lobe (AL). Calcium imaging, using authentic and synthetic odours, shows that the ensemble of AL glomeruli dedicated to either lilac or cotton odour is selectively up- and downregulated in response to mating. A clear cut behavioural modulation as a function of mating is a useful substrate for studies of the neural mechanisms underlying behavioural decisions. Modulation of odour-driven behaviour through concerted regulation of odour maps contributes to our understanding of state-dependent choice and host shifts in insect herbivores. PMID- 22319128 TI - A new algorithm quantifies the roles of wind and midge flight activity in the bluetongue epizootic in northwest Europe. AB - The 2006 bluetongue (BT) outbreak in northwestern Europe had devastating effects on cattle and sheep in that intensively farmed area. The role of wind in disease spread, through its effect on Culicoides dispersal, is still uncertain, and remains unquantified. We examine here the relationship between farm-level infection dates and wind speed and direction within the framework of a novel model involving both mechanistic and stochastic steps. We consider wind as both a carrier of host semio-chemicals, to which midges might respond by upwind flight, and as a transporter of the midges themselves, in a more or less downwind direction. For completeness, we also consider midge movement independent of wind and various combinations of upwind, downwind and random movements. Using stochastic simulation, we are able to explain infection onset at 94 per cent of the 2025 affected farms. We conclude that 54 per cent of outbreaks occurred through (presumably midge) movement of infections over distances of no more than 5 km, 92 per cent over distances of no more than 31 km and only 2 per cent over any greater distances. The modal value for all infections combined is less than 1 km. Our analysis suggests that previous claims for a higher frequency of long distance infections are unfounded. We suggest that many apparent long-distance infections resulted from sequences of shorter-range infections; a 'stepping stone' effect. Our analysis also found that downwind movement (the only sort so far considered in explanations of BT epidemics) is responsible for only 39 per cent of all infections, and highlights the effective contribution to disease spread of upwind midge movement, which accounted for 38 per cent of all infections. The importance of midge flight speed is also investigated. Within the same model framework, lower midge active flight speed (of 0.13 rather than 0.5 m s(-1)) reduced virtually to zero the role of upwind movement, mainly because modelled wind speeds in the area concerned were usually greater than such flight speed. Our analysis, therefore, highlights the need to improve our knowledge of midge flight speed in field situations, which is still very poorly understood. Finally, the model returned an intrinsic incubation period of 8 days, in accordance with the values reported in the literature. We argue that better understanding of the movement of infected insect vectors is an important ingredient in the management of future outbreaks of BT in Europe, and other devastating vector-borne diseases elsewhere. PMID- 22319129 TI - Evidence that ship noise increases stress in right whales. AB - Baleen whales (Mysticeti) communicate using low-frequency acoustic signals. These long-wavelength sounds can be detected over hundreds of kilometres, potentially allowing contact over large distances. Low-frequency noise from large ships (20 200 Hz) overlaps acoustic signals used by baleen whales, and increased levels of underwater noise have been documented in areas with high shipping traffic. Reported responses of whales to increased noise include: habitat displacement, behavioural changes and alterations in the intensity, frequency and intervals of calls. However, it has been unclear whether exposure to noise results in physiological responses that may lead to significant consequences for individuals or populations. Here, we show that reduced ship traffic in the Bay of Fundy, Canada, following the events of 11 September 2001, resulted in a 6 dB decrease in underwater noise with a significant reduction below 150 Hz. This noise reduction was associated with decreased baseline levels of stress-related faecal hormone metabolites (glucocorticoids) in North Atlantic right whales (Eubalaena glacialis). This is the first evidence that exposure to low-frequency ship noise may be associated with chronic stress in whales, and has implications for all baleen whales in heavy ship traffic areas, and for recovery of this endangered right whale population. PMID- 22319130 TI - Sea lice as a density-dependent constraint to salmonid farming. AB - Fisheries catches worldwide have shown no increase over the last two decades, while aquaculture has been booming. To cover the demand for fish in the growing human population, continued high growth rates in aquaculture are needed. A potential constraint to such growth is infectious diseases, as disease transmission rates are expected to increase with increasing densities of farmed fish. Using an extensive dataset from all farms growing salmonids along the Norwegian coast, we document that densities of farmed salmonids surrounding individual farms have a strong effect on farm levels of parasitic sea lice and efforts to control sea lice infections. Furthermore, increased intervention efforts have been unsuccessful in controlling elevated infection levels in high salmonid density areas in 2009-2010. Our results emphasize host density effects of farmed salmonids on the population dynamics of sea lice and suggest that parasitic sea lice represent a potent negative feedback mechanism that may limit sustainable spatial densities of farmed salmonids. PMID- 22319131 TI - Environmental radioactivity studies in the proposed Lambapur and Peddagattu uranium mining areas of Andhra Pradesh, India. AB - The present work was aimed at the establishment of baseline radioactive data in the proposed Lambapur and Peddagattu uranium mining areas in the Andhra Pradesh state, India. The background concentrations of naturally occurring radioactivity in the near-surface soils of the study areas were estimated and the results were analysed. The (238)U concentration in the near-surface soil of the study area was found to vary from 100 to 176 Bq kg(-1), with a mean of 138+/-24 Bq kg(-1). (232)Th in the study area soils was found to vary between 64 and 116 Bq kg(-1), with a mean of 83+/-15 Bq kg(-1). The (40)K concentration was found to vary between 309 and 373 Bq kg(-1), with a mean of 343+/-20 Bq kg(-1). The mean natural background radiation levels were also measured with thermoluminescence (TL) dosimetry technique and with a uR-survey meter, in the villages of the study area. Dose rates measured by TL are found to vary from 1287 to 3363 MUGy y(-1), with a mean of 2509 +/- 424 MUGy y(-1). The dose rates measured in the same villages with a MUR-survey meter were found to be in the range of 1211-3255 MUGy y(-1), with a mean of 2524 +/- 395 MUGy y(-1). The mean radiation levels in the study area are found to be relatively high when compared with (Indian) national and international averages. Correlations among radon, thoron and gamma dose rates were found to be poor. The pre-operational data produced in this work will be useful for comparison with future radiation levels during the proposed uranium mining operations. PMID- 22319132 TI - The prevalence of coronary artery variations on coronary computed tomography angiography. AB - BACKGROUND: Coronary computed tomography angiography (CCTA) can delineate the coronary artery anatomy precisely. Basic knowledge of the normal coronary artery anatomy and familiarity with its common variations are essential in order to assess CCTA accurately. PURPOSE: To determine the prevalence of coronary artery variations detected by 64-slice mutidetector CT. MATERIAL AND METHODS: CCTA images of 2096 patients were evaluated retrospectively. Relatively unusual coronary artery morphological features that were seen in greater than 1% of the study population were classified as variations. RESULTS: Coronary artery circulation was right dominant in 86.6%, left dominant in 9.6%, and balanced in 3.8% of patients. The conus artery arose from the right coronary artery in 83%, or directly from the aorta with a separate ostium in 17% of cases which was much more common in men than women. The sinoatrial node artery originated from the right coronary artery (65.6%) or the circumflex artery (33.7%). The atrioventricular node artery originated from the right coronary artery in 86.4% or the circumflex artery in 13.6% of cases. The left main coronary artery was shorter than 0.5 cm in 4.7% of cases and trifurcated into the intermediate artery in 31.3% of cases. A myocardial bridge was observed in 21.6%, coronary ectasia aneurysm in 2%, dual left anterior descending artery (LAD) type 1 in 1.38%, and a variant of type 1 in 0.1% of cases. The presence of coronary atherosclerosis was higher in patients with coronary ectasia-aneurysm than the patients who did not have coronary ectasia-aneurysm (90.5% vs. 72.2%, P = 0.000). CONCLUSION: CCTA is a non-invasive imaging modality for the depiction of variations of the coronary arteries. The incidence of coronary artery variations is high and various, and readers should be familiar and looking for these conditions during interpretation of CCTA examinations. PMID- 22319133 TI - Assessment of global left ventricular function with dual-source computed tomography in patients with valvular heart disease. AB - BACKGROUND: Left ventricular (LV) function is a vital parameter for prognosis, therapy guidance, and follow-up of cardiovascular disease. Dual-source computed tomography (DSCT) provides an accurate analysis of global LV function. PURPOSE: To assess the performance of DSCT in the determination of global LV functional parameters in comparison with cardiovascular magnetic resonance (CMR) and two dimensional transthoracic echocardiography (2D-TTE) in patients with valvular heart disease (VHD). MATERIAL AND METHODS: A total of 111 patients (58 men, mean age 49.9 years) with known VHD and who underwent DSCT, 2D-TTE, and CMR a period of 2 weeks before undergoing valve surgery were included in this study. LV end systolic volume (ESV), end-diastolic volume (EDV), stroke volume (SV), and ejection fraction (EF) were calculated by DSCT using the threshold-based technique, by 2D-TTE using a modified Simpson's method, and by CMR using Simpson's method. Agreement for parameters of LV global function was determined with the Pearson's correlation coefficient (r) and Bland-Altman analysis. All the DSCT and CMR data-sets were assessed independently by two readers. RESULTS: Fifty of the total 111 patients had aortic VHD, 29 patients had mitral VHD, and 32 patients had mixed aortic and mitral VHD. An excellent inter-observer agreement was seen for the assessment of global LV function using DSCT (r = 0.910-0.983) and CMR (r = 0.854-0.965). An excellent or good correlation (r = 0.93, 0.95, 0.87, and 0.71, respectively, P < 0.001) was noted between the DSCT and 2D-TTE values for EDV, ESV, SV, and EF. EDV (33.7 mL, P < 0.001), ESV (12.1 mL, P < 0.001), SV (21.2 mL, P < 0.001), and EF (1.6%, P = 0.019) were significantly overestimated by DSCT when compared with 2D-TTE. An excellent correlation (r = 0.96, 0.97, 0.91, and 0.94, respectively, P < 0.001) between DSCT and CMR was seen in the evaluation of EDV, ESV, SV, and EF. EDV (15.9 mL, P < 0.001), ESV (7.3 mL, P < 0.001), and SV (8.5 mL, P < 0.001) were significantly underestimated, but EF (1.1%, P = 0.002) was significantly overestimated by DSCT when compared with CMR. CONCLUSION: Our study showed that DSCT measurements of global LV function using the threshold-based technique were highly reproducible and compared more favorably with CMR measurements using Simpson's method than those of 2D-TTE using the modified Simpson's method. DSCT enables accurate quantification of global LV function in patients with VHD. PMID- 22319134 TI - Evolution of the genetic machinery of the visual cycle: a novelty of the vertebrate eye? AB - The discovery in invertebrates of ciliary photoreceptor cells and ciliary (c) opsins established that at least two of the three elements that characterize the vertebrate photoreceptor system were already present before vertebrate evolution. However, the origin of the third element, a series of biochemical reactions known as the "retinoid cycle," remained uncertain. To understand the evolution of the retinoid cycle, I have searched for the genetic machinery of the cycle in invertebrate genomes, with special emphasis on the cephalochordate amphioxus. Amphioxus is closely related to vertebrates, has a fairly prototypical genome, and possesses ciliary photoreceptor cells and c-opsins. Phylogenetic and structural analyses of the amphioxus sequences related with the vertebrate machinery do not support a function of amphioxus proteins in chromophore regeneration but suggest that the genetic machinery of the retinoid cycle arose in vertebrates due to duplications of ancestral nonvisual genes. These results favor the hypothesis that the retinoid cycle machinery was a functional innovation of the primitive vertebrate eye. PMID- 22319135 TI - Transcriptomic evidence for the expression of horizontally transferred algal nuclear genes in the photosynthetic sea slug, Elysia chlorotica. AB - Analysis of the transcriptome of the kleptoplastic sea slug, Elysia chlorotica, has revealed the presence of at least 101 chloroplast-encoded gene sequences and 111 transcripts matching 52 nuclear-encoded genes from the chloroplast donor, Vaucheria litorea. These data clearly show that the symbiotic chloroplasts are translationally active and, of even more interest, that a variety of functional algal genes have been transferred into the slug genome, as has been suggested by earlier indirect experiments. Both the chloroplast- and nuclear-encoded sequences were rare within the E. chlorotica transcriptome, suggesting that their copy numbers and synthesis rates are low, and required both a large amount of sequence data and native algal sequences to find. These results show that the symbiotic chloroplasts residing inside the host molluscan cell are maintained by an interaction of both organellar and host biochemistry directed by the presence of transferred genes. PMID- 22319136 TI - The TRAMP complex shows tRNA editing activity in S. cerevisiae. AB - Transfer RNA (tRNA) editing is a widespread processing phenomenon that alters the sequence of primary transcripts by base substitutions as well as nucleotide deletions and insertions at internal or terminal transcript positions. In the corresponding tRNAs, these events are an important prerequisite for the generation of functional transcripts. Although many editing events are well characterized at the reaction level, it is unclear in most cases from which ancestral activities the modern editing enzymes evolved. Here, we show that in Saccharomyces cerevisiae, the noncanonical poly(A) polymerase Trf4p in the TRAMP complex can be recruited for such an editing reaction at an introduced tRNA transcript. As a distributive polymerase involved in RNA surveillance and quality control, it has a broad substrate spectrum and binds only transiently to the transcripts, limiting the number of added nucleotides at the editing position. These features exactly meet the criteria for an ancestral enzyme of a modern editing activity. Accordingly, our observations are a strong experimental support for the hypothesis that enzymatic promiscuity serves as an evolutionary starting point for the emergence of new functions and activities. PMID- 22319137 TI - Independent domestication of Asian rice followed by gene flow from japonica to indica. AB - Results from studies on the domestication process of Asian rice Oryza sativa have been controversial because of its complicated evolutionary history. Previous studies have yielded two alternative hypotheses about the origin(s) of the two major groups of O. sativa: japonica and indica. One study proposes a single common wild ancestor, whereas the other suggests that there were multiple domestication events of different types of wild rice. Here, we provide clear evidence of the independent domestication of japonica and indica obtained via high-throughput sequencing and a large-scale comparative analysis of two wild rice accessions (W1943 and W0106) and two cultivars (a japonica cultivar called "Nipponbare" and an indica cultivar called "Guangluai-4"). The different domestication processes of the two cultivar groups appear to have led to distinct patterns of molecular evolution in protein-coding regions. The intensity of purifying selection was relaxed only in the japonica group, possibly because of a bottleneck effect. Moreover, a genome-wide comparison between Nipponbare, Guangluai-4, and another indica cultivar (93-11) suggests multiple hybridization events between japonica and indica, both before and after the divergence of the indica cultivars. We found that a large amount of genomic DNA, including domestication-related genes, was transferred from japonica to indica, which might have been important in the development of modern rice. Our study provides an overview of the dynamic process of Asian rice domestication, including independent domestication events and subsequent gene flow. PMID- 22319138 TI - Impact of genetic architecture on the relative rates of X versus autosomal adaptive substitution. AB - Molecular evolutionary theory predicts that the ratio of autosomal to X-linked adaptive substitution (K(A)/K(x)) is primarily determined by the average dominance coefficient of beneficial mutations. Although this theory has profoundly influenced analysis and interpretation of comparative genomic data, its predictions are based upon two unverified assumptions about the genetic basis of adaptation. The theory assumes that 1) the rate of adaptively driven molecular evolution is limited by the availability of beneficial mutations, and 2) the scaling of evolutionary parameters between the X and the autosomes (e.g., the beneficial mutation rate, and the fitness effect distribution of beneficial alleles, per X-linked versus autosomal locus) is constant across molecular evolutionary timescales. Here, we show that the genetic architecture underlying bouts of adaptive substitution can influence both assumptions, and consequently, the theoretical relationship between K(A)/K(x) and mean dominance. Quantitative predictions of prior theory apply when 1) many genomically dispersed genes potentially contribute beneficial substitutions during individual steps of adaptive walks, and 2) the population beneficial mutation rate, summed across the set of potentially contributing genes, is sufficiently small to ensure that adaptive substitutions are drawn from new mutations rather than standing genetic variation. Current research into the genetic basis of adaptation suggests that both assumptions are plausibly violated. We find that the qualitative positive relationship between mean dominance and K(A)/K(x) is relatively robust to the specific conditions underlying adaptive substitution, yet the quantitative relationship between dominance and K(A)/K(x) is quite flexible and context dependent. This flexibility may partially account for the puzzlingly variable X versus autosome substitution patterns reported in the empirical evolutionary genomics literature. The new theory unites the previously separate analysis of adaptation using new mutations versus standing genetic variation and makes several useful predictions about the interaction between genetic architecture, evolutionary genetic constraints, and effective population size in determining the ratio of adaptive substitution between autosomal and X-linked genes. PMID- 22319139 TI - Efficient selection of branch-specific models of sequence evolution. AB - The analysis of extant sequences shows that molecular evolution has been heterogeneous through time and among lineages. However, for a given sequence alignment, it is often difficult to uncover what factors caused this heterogeneity. In fact, identifying and characterizing heterogeneous patterns of molecular evolution along a phylogenetic tree is very challenging, for lack of appropriate methods. Users either have to a priori define groups of branches along which they believe molecular evolution has been similar or have to allow each branch to have its own pattern of molecular evolution. The first approach assumes prior knowledge that is seldom available, and the second requires estimating an unreasonably large number of parameters. Here we propose a convenient and reliable approach where branches get clustered by their pattern of molecular evolution alone, with no need for prior knowledge about the data set under study. Model selection is achieved in a statistical framework and therefore avoids overparameterization. We rely on substitution mapping for efficiency and present two clustering approaches, depending on whether or not we expect neighbouring branches to share more similar patterns of sequence evolution than distant branches. We validate our method on simulations and test it on four previously published data sets. We find that our method correctly groups branches sharing similar equilibrium GC contents in a data set of ribosomal RNAs and recovers expected footprints of selection through dN/dS. Importantly, it also uncovers a new pattern of relaxed selection in a phylogeny of Mantellid frogs, which we are able to correlate to life-history traits. This shows that our programs should be very useful to study patterns of molecular evolution and reveal new correlations between sequence and species evolution. Our programs can run on DNA, RNA, codon, or amino acid sequences with a large set of possible models of substitutions and are available at http://biopp.univ montp2.fr/forge/testnh. PMID- 22319140 TI - Evolution of CRISPs associated with toxicoferan-reptilian venom and mammalian reproduction. AB - Cysteine-rich secretory proteins (CRISPs) are glycoproteins found exclusively in vertebrates and have broad diversified functions. They are hypothesized to play important roles in mammalian reproduction and in reptilian venom, where they disrupt homeostasis of the prey through several mechanisms, including among others, blockage of cyclic nucleotide-gated and voltage-gated ion channels and inhibition of smooth muscle contraction. We evaluated the molecular evolution of CRISPs in toxicoferan reptiles at both nucleotide and protein levels relative to their nonvenomous mammalian homologs. We show that the evolution of CRISP gene in these reptiles is significantly influenced by positive selection and in snakes (omega = 3.84) more than in lizards (omega = 2.33), whereas mammalian CRISPs were under strong negative selection (CRISP1 = 0.55, CRISP2 = 0.40, and CRISP3 = 0.68). The use of ancestral sequence reconstruction, mapping of mutations on the three-dimensional structure, and detailed evaluation of selection pressures suggests that the toxicoferan CRISPs underwent accelerated evolution aided by strong positive selection and directional mutagenesis, whereas their mammalian homologs are constrained by negative selection. Gene and protein-level selection analyses identified 41 positively selected sites in snakes and 14 sites in lizards. Most of these sites are located on the molecular surface (nearly 76% in snakes and 79% in lizards), whereas the backbone of the protein retains a highly conserved structural scaffold. Nearly 46% of the positively selected sites occur in the cysteine-rich domain of the protein. This directional mutagenesis, where the hotspots of mutations are found on the molecular surface and functional domains of the protein, acts as a diversifying mechanism for the exquisite biological targeting of CRISPs in toxicoferan reptiles. Finally, our analyses suggest that the evolution of toxicoferan-CRISP venoms might have been influenced by the specific predatory mechanism employed by the organism. CRISPs in Elapidae, which mostly employ neurotoxins, have experienced less positive selection pressure (omega = 2.86) compared with the "nonvenomous" colubrids (omega = 4.10) that rely on grip and constriction to capture the prey, and the Viperidae, a lineage that mostly employs haemotoxins (omega = 4.19). Relatively lower omega estimates in Anguimorph lizards (omega = 2.33) than snakes (omega = 3.84) suggests that lizards probably depend more on pace and powerful jaws for predation than venom. PMID- 22319141 TI - Resequencing data provide no evidence for a human bottleneck in Africa during the penultimate glacial period. AB - Based on the accumulation of genetic, climatic, and fossil evidence, a central theory in paleoanthropology stipulates that a demographic bottleneck coincided with the origin of our species Homo Sapiens. This theory proposes that anatomically modern humans--which were only present in Africa at the time- experienced a drastic bottleneck during the penultimate glacial age (130-190 kya) when a cold and dry climate prevailed. Two scenarios have been proposed to describe the bottleneck, which involve either a fragmentation of the range occupied by humans or the survival of one small group of humans. Here, we analyze DNA sequence data from 61 nuclear loci sequenced in three African populations using Approximate Bayesian Computation and numerical simulations. In contrast to the bottleneck theory, we show that a simple model without any bottleneck during the penultimate ice age has the greatest statistical support compared with bottleneck models. Although the proposed bottleneck is ancient, occurring at least 130 kya, we can discard the possibility that it did not leave detectable footprints in the DNA sequence data except if the bottleneck involves a less than a 3-fold reduction in population size. Finally, we confirm that a simple model without a bottleneck is able to reproduce the main features of the observed patterns of genetic variation. We conclude that models of Pleistocene refugium for modern human origins now require substantial revision. PMID- 22319142 TI - Origin and evolution of laminin gene family diversity. AB - Laminins are a family of multidomain glycoproteins that are important contributors to the structure of metazoan extracellular matrices. To investigate the origin and evolution of the laminin family, we characterized the full complement of laminin-related genes in the genome of the sponge, Amphimedon queenslandica. As a representative of the Demospongiae, a group consistently placed within the earliest diverging branch of animals by molecular phylogenies, Amphimedon is uniquely placed to provide insight into early steps in the evolution of metazoan gene families. Five Amphimedon laminin-related genes possess the conserved molecular features, and most of the domains found in bilaterian laminins, but all display domain architectures distinct from those of the canonical laminin chain types known from model bilaterians. This finding prompted us to perform a comparative genomic analysis of laminins and related genes from a choanoflagellate and diverse metazoans and to conduct phylogenetic analyses using the conserved Laminin N-terminal domain in order to explore the relationships between genes with distinct architectures. Laminin-like genes appear to have originated in the holozoan lineage (choanoflagellates + metazoans + several other unicellular opisthokont taxa), with several laminin domains originating later and appearing only in metazoan (animal) or eumetazoan (placozoans + ctenophores + cnidarians + bilaterians) laminins. Typical bilaterian alpha, beta, and gamma laminin chain forms arose in the eumetazoan stem and another chain type that is conserved in Amphimedon, the cnidarian, Nematostella vectensis, and the echinoderm, Strongylocentrotus purpuratus, appears to have been lost independently from the placozoan, Trichoplax adhaerens, and from multiple bilaterians. Phylogenetic analysis did not clearly reconstruct relationships between the distinct laminin chain types (with the exception of the alpha chains) but did reveal how several members of the netrin family were generated independently from within the laminin family by duplication and domain shuffling and by domain loss. Together, our results suggest that gene duplication and loss and domain shuffling and loss all played a role in the evolution of the laminin family and contributed to the generation of lineage-specific diversity in the laminin gene complements of extant metazoans. PMID- 22319143 TI - Inferring divergence of context-dependent substitution rates in Drosophila genomes with applications to comparative genomics. AB - Nucleotide substitution is a major evolutionary driving force that can incrementally and stochastically give rise to broad divergence patterns among species. The substitution process at each genomic position is frequently modeled independently of the other positions, although complex interactions between nearby bases are known to significantly affect mutation rates. Here, we study the evolution of 12 fly genomes using new algorithms for accurate inference of parameter-rich substitution models. By comparing models between lineages, we reveal the evolutionary histories of substitution rates at different flanking nucleotide contexts. We demonstrate these driving forces of molecular evolution to be constantly changing, suggesting that neutral drift of mutation rates is an important factor in the evolution of genomes and their sequence composition. This observation is used to develop a scalable approach for parameter-rich comparative genomics. By screening short DNA sequences, we demonstrate how homeoboxes and other transcription factor binding motifs are highly conserved based on our parameter-rich models but not according to standard conservation assays. With the increasing availability of genome sequences, rich substitution models become an attractive and practical approach for evolutionary analysis in general and comparative genomics in particular. PMID- 22319144 TI - Low evolutionary diversification in a widespread and abundant uncultured protist (MAST-4). AB - Recent culture-independent studies of marine planktonic protists have unveiled a large diversity at all phylogenetic scales and the existence of novel groups. MAST-4 represents one of these novel uncultured lineages, and it is composed of small (~2 MUm) bacterivorous eukaryotes that are widely distributed in marine systems. MAST-4 accounts for a significant fraction of the marine heterotrophic flagellates at the global level, playing key roles in the marine ecological network. In this study, we investigated the diversity of MAST-4, aiming to assess its limits and structure. Using ribosomal DNA (rDNA) sequences obtained in this study (both pyrosequencing reads and clones with large rDNA operon coverage), complemented with GenBank sequences, we show that MAST-4 is composed of only five main clades, which are well supported by small subunit and large subunit phylogenies. The differences in the conserved regions of the internal transcribed spacers 1 and 2 (ITS1 and ITS2) secondary structures strongly suggest that these five clades are different biological species. Based on intraclade divergence, ITS secondary structures and comparisons of ITS1 and ITS2 trees, we did not find evidence of more than one species within clade A, whereas as many as three species might be present within other clades. Overall, the genetic divergence of MAST-4 was surprisingly low for an organism with a global population size estimated to be around 10(24), indicating a very low evolutionary diversification within the group. PMID- 22319146 TI - Multihost experimental evolution of a plant RNA virus reveals local adaptation and host-specific mutations. AB - For multihost pathogens, adaptation to multiple hosts has important implications for both applied and basic research. At the applied level, it is one of the main factors determining the probability and the severity of emerging disease outbreaks. At the basic level, it is thought to be a key mechanism for the maintenance of genetic diversity both in host and pathogen species. Using Tobacco etch potyvirus (TEV) and four natural hosts, we have designed an evolution experiment whose strength and novelty are the use of complex multicellular host organism as hosts and a high level of replication of different evolutionary histories and lineages. A pattern of local adaptation, characterized by a higher infectivity and virulence on host(s) encountered during the experimental evolution was found. Local adaptation only had a cost in terms of performance on other hosts in some cases. We could not verify the existence of a cost for generalists, as expected to arise from antagonistic pleiotropy and other genetic mechanisms generating a fitness trade-off between hosts. This observation confirms that this classical theoretical prediction lacks empirical support. We discuss the reasons for this discrepancy between theory and experiment in the light of our results. The analysis of full genome consensus sequences of the evolved lineages established that all mutations shared between lineages were host specific. A low degree of parallel evolution was observed, possibly reflecting the various adaptive pathways available for TEV in each host. Altogether, these results reveal a strong adaptive potential of TEV to new hosts without severe evolutionary constraints. PMID- 22319145 TI - The voltage-gated potassium channel subfamily KQT member 4 (KCNQ4) displays parallel evolution in echolocating bats. AB - Bats are the only mammals that use highly developed laryngeal echolocation, a sensory mechanism based on the ability to emit laryngeal sounds and interpret the returning echoes to identify objects. Although this capability allows bats to orientate and hunt in complete darkness, endowing them with great survival advantages, the genetic bases underlying the evolution of bat echolocation are still largely unknown. Echolocation requires high-frequency hearing that in mammals is largely dependent on somatic electromotility of outer hair cells. Then, understanding the molecular evolution of outer hair cell genes might help to unravel the evolutionary history of echolocation. In this work, we analyzed the molecular evolution of two key outer hair cell genes: the voltage-gated potassium channel gene KCNQ4 and CHRNA10, the gene encoding the alpha10 nicotinic acetylcholine receptor subunit. We reconstructed the phylogeny of bats based on KCNQ4 and CHRNA10 protein and nucleotide sequences. A phylogenetic tree built using KCNQ4 amino acid sequences showed that two paraphyletic clades of laryngeal echolocating bats grouped together, with eight shared substitutions among particular lineages. In addition, our analyses indicated that two of these parallel substitutions, M388I and P406S, were probably fixed under positive selection and could have had a strong functional impact on KCNQ4. Moreover, our results indicated that KCNQ4 evolved under positive selection in the ancestral lineage leading to mammals, suggesting that this gene might have been important for the evolution of mammalian hearing. On the other hand, we found that CHRNA10, a gene that evolved adaptively in the mammalian lineage, was under strong purifying selection in bats. Thus, the CHRNA10 amino acid tree did not show echolocating bat monophyly and reproduced the bat species tree. These results suggest that only a subset of hearing genes could underlie the evolution of echolocation. The present work continues to delineate the genetic bases of echolocation and ultrasonic hearing in bats. PMID- 22319147 TI - Collodictyon--an ancient lineage in the tree of eukaryotes. AB - The current consensus for the eukaryote tree of life consists of several large assemblages (supergroups) that are hypothesized to describe the existing diversity. Phylogenomic analyses have shed light on the evolutionary relationships within and between supergroups as well as placed newly sequenced enigmatic species close to known lineages. Yet, a few eukaryote species remain of unknown origin and could represent key evolutionary forms for inferring ancient genomic and cellular characteristics of eukaryotes. Here, we investigate the evolutionary origin of the poorly studied protist Collodictyon (subphylum Diphyllatia) by sequencing a cDNA library as well as the 18S and 28S ribosomal DNA (rDNA) genes. Phylogenomic trees inferred from 124 genes placed Collodictyon close to the bifurcation of the "unikont" and "bikont" groups, either alone or as sister to the potentially contentious excavate Malawimonas. Phylogenies based on rDNA genes confirmed that Collodictyon is closely related to another genus, Diphylleia, and revealed a very low diversity in environmental DNA samples. The early and distinct origin of Collodictyon suggests that it constitutes a new lineage in the global eukaryote phylogeny. Collodictyon shares cellular characteristics with Excavata and Amoebozoa, such as ventral feeding groove supported by microtubular structures and the ability to form thin and broad pseudopods. These may therefore be ancient morphological features among eukaryotes. Overall, this shows that Collodictyon is a key lineage to understand early eukaryote evolution. PMID- 22319148 TI - A trans-specific polymorphism in ZC3HAV1 is maintained by long-standing balancing selection and may confer susceptibility to multiple sclerosis. AB - The human ZC3HAV1 gene encodes an antiviral protein. The longest splicing isoform of ZC3HAV1 contains a C-terminal PARP-like domain, which has evolved under positive selection in primates. We analyzed the evolutionary history of this same domain in humans and in Pan troglodytes. We identified two variants that segregate in both humans and chimpanzees; one of them (rs3735007) does not occur at a hypermutable site and accounts for a nonsynonymous substitution (Thr851Ile). The probability that the two trans-specific polymorphisms have occurred independently in the two lineages was estimated to be low (P = 0.0054), suggesting that at least one of them has arisen before speciation and has been maintained by selection. Population genetic analyses in humans indicated that the region surrounding the shared variants displays strong evidences of long-standing balancing selection. Selection signatures were also observed in a chimpanzee population sample. Inspection of 1000 Genomes data confirmed these findings but indicated that search for selection signatures using low-coverage whole-genome data may need masking of repetitive sequences. A case-control study of more than 1,000 individuals from mainland Italy indicated that the Thr851Ile SNP is significantly associated with susceptibility to multiple sclerosis (MS) (odds ratio [OR] = 1.47, 95% confidence intervals [CI]: 1.08-1.99, P = 0.011). This finding was confirmed in a larger sample of 4,416 Sardinians cases/controls (OR = 1.18, 95% CI: 1.037-1.344, P = 0.011), but not in a population from Belgium. We provide one of the first instances of human/chimpanzee trans-specific coding variant located outside the major histocompatibility complex region. The selective pressure is likely to be virus driven; in modern populations, this variant associates with susceptibility to MS, possibly via the interaction with environmental factors. PMID- 22319149 TI - Phylogeography and population dynamics of dengue viruses in the Americas. AB - Changes in Dengue virus (DENV) disease patterns in the Americas over recent decades have been attributed, at least in part, to repeated introduction of DENV strains from other regions, resulting in a shift from hypoendemicity to hyperendemicity. Using newly sequenced DENV-1 and DENV-3 envelope (E) gene isolates from 11 Caribbean countries, along with sequences available on GenBank, we sought to document the population genetic and spatiotemporal transmission histories of the four main invading DENV genotypes within the Americas and investigate factors that influence the rate and intensity of DENV transmission. For all genotypes, there was an initial invasion phase characterized by rapid increases in genetic diversity, which coincided with the first confirmed cases of each genotype in the region. Rapid geographic dispersal occurred upon each genotype's introduction, after which individual lineages were locally maintained, and gene flow was primarily observed among neighboring and nearby countries. There were, however, centers of viral diversity (Barbados, Puerto Rico, Colombia, Suriname, Venezuela, and Brazil) that were repeatedly involved in gene flow with more distant locations. For DENV-1 and DENV-2, we found that a "distance informed" model, which posits that the intensity of virus movement between locations is inversely proportional to the distance between them, provided a better fit than a model assuming equal rates of movement between all pairs of countries. However, for DENV-3 and DENV-4, the more stochastic "equal rates" model was preferred. PMID- 22319150 TI - Allelic imbalance in Drosophila hybrid heads: exons, isoforms, and evolution. AB - Unraveling how regulatory divergence contributes to species differences and adaptation requires identifying functional variants from among millions of genetic differences. Analysis of allelic imbalance (AI) reveals functional genetic differences in cis regulation and has demonstrated differences in cis regulation within and between species. Regulatory mechanisms are often highly conserved, yet differences between species in gene expression are extensive. What evolutionary forces explain widespread divergence in cis regulation? AI was assessed in Drosophila melanogaster-Drosophila simulans hybrid female heads using RNA-seq technology. Mapping bias was virtually eliminated by using genotype specific references. Allele representation in DNA sequencing was used as a prior in a novel Bayesian model for the estimation of AI in RNA. Cis regulatory divergence was common in the organs and tissues of the head with 41% of genes analyzed showing significant AI. Using existing population genomic data, the relationship between AI and patterns of sequence evolution was examined. Evidence of positive selection was found in 30% of cis regulatory divergent genes. Genes involved in defense, RNAi/RISC complex genes, and those that are sex regulated are enriched among adaptively evolving cis regulatory divergent genes. For genes in these groups, adaptive evolution may play a role in regulatory divergence between species. However, there is no evidence that adaptive evolution drives most of the cis regulatory divergence that is observed. The majority of genes showed patterns consistent with stabilizing selection and neutral evolutionary processes. PMID- 22319151 TI - Younger genes are less likely to be essential than older genes, and duplicates are less likely to be essential than singletons of the same age. AB - Recently duplicated genes are believed to often overlap in function and expression. A priori, they are thus less likely to be essential. Although this was indeed observed in yeast, mouse singletons and duplicates were reported to be equally often essential. This contradiction can only partly be explained by experimental biases. We herein show that older genes (i.e., genes with earlier phyletic origin) are more likely to be essential, regardless of their duplication status. At a given phyletic gene age, duplicates are always less likely to be essential compared with singletons. The "paradoxical" high essentiality among mouse gene duplicates is then caused by different age profiles of singletons and duplicates, with the latter tending to be derived from older genes. PMID- 22319152 TI - Sampling the conformational energy landscape of a hyperthermophilic protein by engineering key substitutions. AB - Proteins exist as a dynamic ensemble of interconverting substates, which defines their conformational energy landscapes. Recent work has indicated that mutations that shift the balance between conformational substates (CSs) are one of the main mechanisms by which proteins evolve new functions. In the present study, we probe this assertion by examining phenotypic protein adaptation to extreme conditions, using the allosteric tetrameric lactate dehydrogenase (LDH) from the hyperthermophilic bacterium Thermus thermophilus (Tt) as a model enzyme. In the presence of fructose 1, 6 bis-phosphate (FBP), allosteric LDHs catalyze the conversion of pyruvate to lactate with concomitant oxidation of nicotinamide adenine dinucleotide, reduced form (NADH). The catalysis involves a structural transition between a low-affinity inactive "T-state" and a high-affinity active "R-state" with bound FBP. During this structural transition, two important residues undergo changes in their side chain conformations. These are R171 and H188, which are involved in substrate and FBP binding, respectively. We designed two mutants of Tt-LDH with one ("1-Mut") and five ("5-Mut") mutations distant from the active site and characterized their catalytic, dynamical, and structural properties. In 1-Mut Tt-LDH, without FBP, the K(m)(Pyr) is reduced compared with that of the wild type, which is consistent with a complete shifting of the CS equilibrium of H188 to that observed in the R-state. By contrast, the CS populations of R171, k(cat) and protein stability are little changed. In 5-Mut Tt LDH, without FBP, K(m)(Pyr) approaches the values it has with FBP and becomes almost temperature independent, k(cat) increases substantially, and the CS populations of R171 shift toward those of the R-state. These changes are accompanied by a decrease in protein stability at higher temperature, which is consistent with an increased flexibility at lower temperature. Together, these results show that the thermal properties of an enzyme can be strongly modified by only a few or even a single mutation, which serve to alter the equilibrium and, hence, the relative populations of functionally important native-state CSs, without changing the nature of the CSs themselves. They also provide insights into the types of mutational pathways by which protein adaptation to temperature is achieved. PMID- 22319153 TI - Multiple adaptive losses of alanine-glyoxylate aminotransferase mitochondrial targeting in fruit-eating bats. AB - The enzyme alanine-glyoxylate aminotransferase 1 (AGT) functions to detoxify glyoxylate before it is converted into harmful oxalate. In mammals, mitochondrial targeting of AGT in carnivorous species versus peroxisomal targeting in herbivores is controlled by two signal peptides that correspond to these respective organelles. Differential expression of the mitochondrial targeting sequence (MTS) is considered an adaptation to diet-specific subcellular localization of glyoxylate precursors. Bats are an excellent group in which to study adaptive changes in dietary enzymes; they show unparalleled mammalian dietary diversification as well as independent origins of carnivory, frugivory, and nectarivory. We studied the AGT gene in bats and other mammals with diverse diets and found that the MTS has been lost in unrelated lineages of frugivorous bats. Conversely, species exhibiting piscivory, carnivory, insectivory, and sanguinivory possessed intact MTSs. Detected positive selection in the AGT of ancestral fruit bats further supports adaptations related to evolutionary changes in diet. PMID- 22319154 TI - Evolution of bioluminescence in marine planktonic copepods. AB - Copepods are the dominant taxa in zooplankton communities of the ocean worldwide. Although bioluminescence of certain copepods has been known for more than a 100 years, there is very limited information about the structure and evolutionary history of copepod luciferase genes. Here, we report the cDNA sequences of 11 copepod luciferases isolated from the superfamily Augaptiloidea in the order Calanoida. Highly conserved amino acid residues in two similar repeat sequences were confirmed by the multiple alignment of all known copepod luciferases. Copepod luciferases were classified into two groups of Metridinidae and Heterorhabdidae/Lucicutiidae families based on phylogenetic analyses, with confirmation of the interrelationships within the Calanoida using 18S ribosomal DNA sequences. The large diversity in the specific activity of planktonic homogenates and copepod luciferases that we were able to express in mammalian cultured cells illustrates the importance of bioluminescence as a protective function against predators. We also discuss the relationship between the evolution of copepod bioluminescence and the aspects of their ecological characteristics, such as swimming activity and vertical habitat. PMID- 22319155 TI - Crohn's disease risk alleles on the NOD2 locus have been maintained by natural selection on standing variation. AB - Risk alleles for complex diseases are widely spread throughout human populations. However, little is known about the geographic distribution and frequencies of risk alleles, which may contribute to differences in disease susceptibility and prevalence among populations. Here, we focus on Crohn's disease (CD) as a model for the evolutionary study of complex disease alleles. Recent genome-wide association studies and classical linkage analyses have identified more than 70 susceptible genomic regions for CD in Europeans, but only a few have been confirmed in non-European populations. Our analysis of eight European-specific susceptibility genes using HapMap data shows that at the NOD2 locus the CD-risk alleles are linked with a haplotype specific to CEU at a frequency that is significantly higher compared with the entire genome. We subsequently examined nine global populations and found that the CD-risk alleles spread through hitchhiking with a high-frequency haplotype (H1) exclusive to Europeans. To examine the neutrality of NOD2, we performed phylogenetic network analyses, coalescent simulation, protein structural prediction, characterization of mutation patterns, and estimations of population growth and time to most recent common ancestor (TMRCA). We found that while H1 was significantly prevalent in European populations, the H1 TMRCA predated human migration out of Africa. H1 is likely to have undergone negative selection because 1) the root of H1 genealogy is defined by a preexisting amino acid substitution that causes serious conformational changes to the NOD2 protein, 2) the haplotype has almost become extinct in Africa, and 3) the haplotype has not been affected by the recent European expansion reflected in the other haplotypes. Nevertheless, H1 has survived in European populations, suggesting that the haplotype is advantageous to this group. We propose that several CD-risk alleles, which destabilize and disrupt the NOD2 protein, have been maintained by natural selection on standing variation because the deleterious haplotype of NOD2 is advantageous in diploid individuals due to heterozygote advantage and/or intergenic interactions. PMID- 22319156 TI - Dozens of toxin-related genes are expressed in a nontoxic strain of the dinoflagellate Heterocapsa circularisquama. AB - The dinoflagellate Heterocapsa circularisquama is lethal to a variety of marine organisms, in particular, commercially important farmed bivalves. Unlike most dinoflagellate toxins, which are polyketides, the only described toxin from H. circularisquama (H2-a) is a porphyrin derivative that functions in light. It is unknown whether H2-a is produced specifically for its lytic properties. We searched for toxin-related genes in the transcriptome of a nontoxic strain of H. circularisquama, and surprisingly found the richest set of toxin-related genes yet described in dinoflagellates. There are 87 distinct expressed sequence tag contigs that encode polyketide synthases and nonribosomal peptide synthases, as well as 8 contigs that are involved in porphyrin biosynthesis. Phylogenomic analysis shows that many toxin-related genes are widely distributed among dinoflagellates. Our data likely indicate a variety of unknown metabolic functions for the toxin-related genes in H. circularisquama because they were identified in a nontoxic strain raised in unialgal culture. PMID- 22319157 TI - Global genetic variation at OAS1 provides evidence of archaic admixture in Melanesian populations. AB - Recent analysis of DNA extracted from two Eurasian forms of archaic human shows that more genetic variants are shared with humans currently living in Eurasia than with anatomically modern humans in sub-Saharan Africa. Although these genome wide average measures of genetic similarity are consistent with the hypothesis of archaic admixture in Eurasia, analyses of individual loci exhibiting the signal of archaic introgression are needed to test alternative hypotheses and investigate the admixture process. Here, we provide a detailed sequence analysis of the innate immune gene OAS1, a locus with a divergent Melanesian haplotype that is very similar to the Denisova sequence from the Altai region of Siberia. We resequenced a 7-kb region encompassing the OAS1 gene in 88 individuals from six Old World populations (San, Biaka, Mandenka, French Basque, Han Chinese, and Papua New Guineans) and discovered previously unknown and ancient genetic variation. The 5' region of this gene has unusual patterns of diversity, including 1) higher levels of nucleotide diversity in Papuans than in sub-Saharan Africans, 2) very deep ancestry with an estimated time to the most recent common ancestor of >3 myr, and 3) a basal branching pattern with Papuan individuals on either side of the rooted network. A global geographic survey of >1,500 individuals showed that the divergent Papuan haplotype is nearly restricted to populations from eastern Indonesia and Melanesia. Polymorphic sites within this haplotype are shared with the draft Denisova genome over a span of ~90 kb and are associated with an extended block of linkage disequilibrium, supporting the hypothesis that this haplotype introgressed from an archaic source that likely lived in Eurasia. PMID- 22319158 TI - Sex chromosomes evolved from independent ancestral linkage groups in winged insects. AB - The evolution of a pair of chromosomes that differ in appearance between males and females (heteromorphic sex chromosomes) has occurred repeatedly across plants and animals. Recent work has shown that the male heterogametic (XY) and female heterogametic (ZW) sex chromosomes evolved independently from different pairs of homomorphic autosomes in the common ancestor of birds and mammals but also that X and Z chromosomes share many convergent molecular features. However, little is known about how often heteromorphic sex chromosomes have either evolved convergently from different autosomes or in parallel from the same pair of autosomes and how universal patterns of molecular evolution on sex chromosomes really are. Among winged insects with sequenced genomes, there are male heterogametic species in both the Diptera (e.g., Drosophila melanogaster) and the Coleoptera (Tribolium castaneum), female heterogametic species in the Lepidoptera (Bombyx mori), and haplodiploid species in the Hymenoptera (e.g., Nasonia vitripennis). By determining orthologous relationships among genes on the X and Z chromosomes of insects with sequenced genomes, we are able to show that these chromosomes are not homologous to one another but are homologous to autosomes in each of the other species. These results strongly imply that heteromorphic sex chromosomes have evolved independently from different pairs of ancestral chromosomes in each of the insect orders studied. We also find that the convergently evolved X chromosomes of Diptera and Coleoptera share genomic features with each other and with vertebrate X chromosomes, including excess gene movement from the X to the autosomes. However, other patterns of molecular evolution--such as increased codon bias, decreased gene density, and the paucity of male-biased genes on the X--differ among the insect X and Z chromosomes. Our results provide evidence for both differences and nearly universal similarities in patterns of evolution among independently derived sex chromosomes. PMID- 22319159 TI - Flagellin perception varies quantitatively in Arabidopsis thaliana and its relatives. AB - Much is known about the evolution of plant immunity components directed against specific pathogen strains: They show pervasive functional variation and have the potential to coevolve with pathogen populations. However, plants are effectively protected against most microbes by generalist immunity components that detect conserved pathogen-associated molecular patterns (PAMPs) and control the onset of PAMP-triggered immunity. In Arabidopsis thaliana, the receptor kinase flagellin sensing 2 (FLS2) confers recognition of bacterial flagellin (flg22) and activates a manifold defense response. To decipher the evolution of this system, we performed functional assays across a large set of A. thaliana genotypes and Brassicaceae relatives. We reveal extensive variation in flg22 perception, most of which results from changes in protein abundance. The observed variation correlates with both the severity of elicited defense responses and bacterial proliferation. We analyzed nucleotide variation segregating at FLS2 in A. thaliana and detected a pattern of variation suggestive of the rapid fixation of a novel adaptive allele. However, our study also shows that evolution at the receptor locus alone does not explain the evolution of flagellin perception; instead, components common to pathways downstream of PAMP perception likely contribute to the observed quantitative variation. Within and among close relatives, PAMP perception evolves quantitatively, which contrasts with the changes in recognition typically associated with the evolution of R genes. PMID- 22319160 TI - An improved likelihood ratio test for detecting site-specific functional divergence among clades of protein-coding genes. AB - Maximum likelihood codon substitution models have proven useful for studying when and how protein function evolves, but they have recently been criticized on a number of fronts. The strengths and weaknesses of such methods must therefore be identified and improved upon. Here, using simulations, we show that the Clade model C versus M1a test for functional divergence among clades is prone to false positives under simple evolutionary conditions. We then propose a new null model (M2a_rel) that better accounts for among-site variation in selective constraint. We show that the revised test has an improved false-positive rate and good power. Applying this test to previously analyzed data sets of primate ribonucleases and mammalian rhodopsins reveals that some conclusions may have been misled by the original method. The improved test should prove useful for identifying patterns of divergence in selective constraint among paralogous gene families and among orthologs from ecologically divergent species. PMID- 22319161 TI - Evidence for widespread positive and purifying selection across the European rabbit (Oryctolagus cuniculus) genome. AB - The nearly neutral theory of molecular evolution predicts that the efficacy of both positive and purifying selection is a function of the long-term effective population size (N(e)) of a species. Under this theory, the efficacy of natural selection should increase with N(e). Here, we tested this simple prediction by surveying ~1.5 to 1.8 Mb of protein coding sequence in the two subspecies of the European rabbit (Oryctolagus cuniculus algirus and O. c. cuniculus), a mammal species characterized by high levels of nucleotide diversity and N(e) estimates for each subspecies on the order of 1 * 10(6). When the segregation of slightly deleterious mutations and demographic effects were taken into account, we inferred that >60% of amino acid substitutions on the autosomes were driven to fixation by positive selection. Moreover, we inferred that a small fraction of new amino acid mutations (<4%) are effectively neutral (defined as 0 < N(e)s < 1) and that this fraction was negatively correlated with a gene's expression level. Consistent with models of recurrent adaptive evolution, we detected a negative correlation between levels of synonymous site polymorphism and the rate of protein evolution, although the correlation was weak and nonsignificant. No systematic X chromosome-autosome difference was found in the efficacy of selection. For example, the proportion of adaptive substitutions was significantly higher on the X chromosome compared with the autosomes in O. c. algirus but not in O. c. cuniculus. Our findings support widespread positive and purifying selection in rabbits and add to a growing list of examples suggesting that differences in N(e) among taxa play a substantial role in determining rates and patterns of protein evolution. PMID- 22319162 TI - Phylo-MCOA: a fast and efficient method to detect outlier genes and species in phylogenomics using multiple co-inertia analysis. AB - Full genome data sets are currently being explored on a regular basis to infer phylogenetic trees, but there are often discordances among the trees produced by different genes. An important goal in phylogenomics is to identify which individual gene and species produce the same phylogenetic tree and are thus likely to share the same evolutionary history. On the other hand, it is also essential to identify which genes and species produce discordant topologies and therefore evolve in a different way or represent noise in the data. The latter are outlier genes or species and they can provide a wealth of information on potentially interesting biological processes, such as incomplete lineage sorting, hybridization, and horizontal gene transfers. Here, we propose a new method to explore the genomic tree space and detect outlier genes and species based on multiple co-inertia analysis (MCOA), which efficiently captures and compares the similarities in the phylogenetic topologies produced by individual genes. Our method allows the rapid identification of outlier genes and species by extracting the similarities and discrepancies, in terms of the pairwise distances, between all the species in all the trees, simultaneously. This is achieved by using MCOA, which finds successive decomposition axes from individual ordinations (i.e., derived from distance matrices) that maximize a covariance function. The method is freely available as a set of R functions. The source code and tutorial can be found online at http://phylomcoa.cgenomics.org. PMID- 22319163 TI - Retroposon insertion patterns of neoavian birds: strong evidence for an extensive incomplete lineage sorting era. AB - More than 150 Ma, the avian lineage separated from that of other dinosaurs and later diversified into the more than 10,000 species extant today. The early neoavian bird radiations most likely occurred in the late Cretaceous (more than 65 Ma) but left behind few if any molecular signals of their archaic evolutionary past. Retroposed elements, once established in an ancestral population, are highly valuable, virtually homoplasy-free markers of species evolution; after applying stringent orthology criteria, their phylogenetically informative presence/absence patterns are free of random noise and independent of evolutionary rate or nucleotide composition effects. We screened for early neoavian orthologous retroposon insertions and identified six markers with conflicting presence/absence patterns, whereas six additional retroposons established before or after the presumed major neoavian radiation show consistent phylogenetic patterns. The exceptionally frequent conflicting retroposon presence/absence patterns of neoavian orders are strong indicators of an extensive incomplete lineage sorting era, potentially induced by an early rapid successive speciation of ancestral Neoaves. PMID- 22319165 TI - Plastid sequences contribute to some plant mitochondrial genes. AB - DNA of plastid (chloroplast) origin comprises between 1% and 10% of the mitochondrial genomes of higher plants, but functions are currently considered to be limited to rare instances where plastid tRNA genes have replaced their mitochondrial counterparts, where short patches of mitochondrial genes evolved using their homologous plastidic copies by gene conversion or where a new promoter region is created. Here, we show that, in some angiosperms, plastid derived DNA in mitochondrial genomes (also called mtpt for mitochondrial plastid DNA) contributes codons to unrelated mitochondrial protein-coding sequences and may also have a role in posttranscriptional RNA processing. We determined that these transfers of plastid DNA occurred a few to 150 Ma and that mtpts can sometimes remain dormant many millions of years before contributing to the mitochondrial proteome. PMID- 22319164 TI - Evolution of the globin gene family in deuterostomes: lineage-specific patterns of diversification and attrition. AB - In the Metazoa, globin proteins display an underlying unity in tertiary structure that belies an extraordinary diversity in primary structures, biochemical properties, and physiological functions. Phylogenetic reconstructions can reveal which of these functions represent novel, lineage-specific innovations, and which represent ancestral functions that are shared with homologous globin proteins in other eukaryotes and even prokaryotes. To date, our understanding of globin diversity in deuterostomes has been hindered by a dearth of genomic sequence data from the Ambulacraria (echinoderms + hemichordates), the sister group of chordates, and the phylum Xenacoelomorpha, which includes xenoturbellids, acoelomorphs, and nemertodermatids. Here, we report the results of a phylogenetic and comparative genomic analysis of the globin gene repertoire of deuterostomes. We first characterized the globin genes of the acorn worm, Saccoglossus kowalevskii, a representative of the phylum Hemichordata. We then integrated genomic sequence data from the acorn worm into a comprehensive analysis of conserved synteny and phylogenetic relationships among globin genes from representatives of the eight lineages that comprise the superphylum Deuterostomia. The primary aims were 1) to unravel the evolutionary history of the globin gene superfamily in deuterostomes and 2) to use the estimated phylogeny to gain insights into the functional evolution of deuterostome globins. Results of our analyses indicate that the deuterostome common ancestor possessed a repertoire of at least four distinct globin paralogs and that different subsets of these ancestral genes have been retained in each of the descendant organismal lineages. In each major deuterostome group, a different subset of ancestral precursor genes underwent lineage-specific expansions of functional diversity through repeated rounds of gene duplication and divergence. By integrating results of the phylogenetic analysis with available functional data, we discovered that circulating oxygen-transport hemoglobins evolved independently in several deuterostome lineages and that intracellular nerve globins evolved independently in chordates and acoelomorph worms. PMID- 22319166 TI - Cryptic MHC polymorphism revealed but not explained by selection on the class IIb peptide-binding region. AB - The immune genes of the major histocompatibility complex (MHC) are characterized by extraordinarily high levels of nucleotide and haplotype diversity. This variation is maintained by pathogen-mediated balancing selection that is operating on the peptide-binding region (PBR). Several recent studies have found, however, that some populations possess large clusters of alleles that are translated into virtually identical proteins. Here, we address the question of how this nucleotide polymorphism is maintained with little or no functional variation for selection to operate on. We investigate circa 750-850 bp of MHC class II DAB genes in four wild populations of the guppy Poecilia reticulata. By sequencing an extended region, we uncovered 40.9% more sequences (alleles), which would have been missed if we had amplified the exon 2 alone. We found evidence of several gene conversion events that may have homogenized sequence variation. This reduces the visible copy number variation (CNV) and can result in a systematic underestimation of the CNV in studies of the MHC and perhaps other multigene families. We then focus on a single cluster, which comprises 27 (of a total of 66) sequences. These sequences are virtually identical and show no signal of selection. We use microsatellites to reconstruct the populations' demography and employ simulations to examine whether so many similar nucleotide sequences can be maintained in the populations. Simulations show that this variation does not behave neutrally. We propose that selection operates outside the PBR, for example, on linked immune genes or on the "sheltered load" that is thought to be associated to the MHC. Future studies on the MHC would benefit from extending the amplicon size to include polymorphisms outside the exon with the PBR. This may capture otherwise cryptic haplotype variation and CNV, and it may help detect other regions in the MHC that are under selection. PMID- 22319168 TI - Partitionfinder: combined selection of partitioning schemes and substitution models for phylogenetic analyses. AB - In phylogenetic analyses of molecular sequence data, partitioning involves estimating independent models of molecular evolution for different sets of sites in a sequence alignment. Choosing an appropriate partitioning scheme is an important step in most analyses because it can affect the accuracy of phylogenetic reconstruction. Despite this, partitioning schemes are often chosen without explicit statistical justification. Here, we describe two new objective methods for the combined selection of best-fit partitioning schemes and nucleotide substitution models. These methods allow millions of partitioning schemes to be compared in realistic time frames and so permit the objective selection of partitioning schemes even for large multilocus DNA data sets. We demonstrate that these methods significantly outperform previous approaches, including both the ad hoc selection of partitioning schemes (e.g., partitioning by gene or codon position) and a recently proposed hierarchical clustering method. We have implemented these methods in an open-source program, PartitionFinder. This program allows users to select partitioning schemes and substitution models using a range of information-theoretic metrics (e.g., the Bayesian information criterion, akaike information criterion [AIC], and corrected AIC). We hope that PartitionFinder will encourage the objective selection of partitioning schemes and thus lead to improvements in phylogenetic analyses. PartitionFinder is written in Python and runs under Mac OSX 10.4 and above. The program, source code, and a detailed manual are freely available from www.robertlanfear.com/partitionfinder. PMID- 22319167 TI - Evolution of a membrane protein regulon in Saccharomyces. AB - Expression variation is widespread between species. The ability to distinguish regulatory change driven by natural selection from the consequences of neutral drift remains a major challenge in comparative genomics. In this work, we used observations of mRNA expression and promoter sequence to analyze signatures of selection on groups of functionally related genes in Saccharomycete yeasts. In a survey of gene regulons with expression divergence between Saccharomyces cerevisiae and S. paradoxus, we found that most were subject to variation in trans-regulatory factors that provided no evidence against a neutral model. However, we identified one regulon of membrane protein genes controlled by unlinked cis- and trans-acting determinants with coherent effects on gene expression, consistent with a history of directional, nonneutral evolution. For this membrane protein group, S. paradoxus alleles at regulatory loci were associated with elevated expression and altered stress responsiveness relative to other yeasts. In a phylogenetic comparison of promoter sequences of the membrane protein genes between species, the S. paradoxus lineage was distinguished by a short branch length, indicative of strong selective constraint. Likewise, sequence variants within the S. paradoxus population, but not across strains of other yeasts, were skewed toward low frequencies in promoters of genes in the membrane protein regulon, again reflecting strong purifying selection. Our results support a model in which a distinct expression program for the membrane protein genes in S. paradoxus has been preferentially maintained by negative selection as the result of an increased importance to organismal fitness. These findings illustrate the power of integrating expression- and sequence-based tests of natural selection in the study of evolutionary forces that underlie regulatory change. PMID- 22319169 TI - Life history shapes trait heredity by accumulation of loss-of-function alleles in yeast. AB - A fundamental question in biology is whether variation in organisms primarily emerges as a function of adaptation or as a function of neutral genetic drift. Trait variation in the model organism baker's yeast follows population bottlenecks rather than environmental boundaries suggesting that it primarily results from genetic drift. Based on the yeast life history, we hypothesized that population-specific loss-of-function mutations emerging in genes recently released from selection is the predominant cause of trait variation within the species. As retention of one functional copy of a gene in diploid yeasts is typically sufficient to maintain completely unperturbed performance, we also conjectured that a crossing of natural yeasts from populations with different loss-of-function mutations would provide a further efficient test bed for this hypothesis. Charting the first species-wide map of trait inheritance in a eukaryotic organism, we found trait heredity to be strongly biased toward diploid hybrid performance exactly mimicking the performance of the best of the parents, as expected given a complete dominance of functional over nonfunctional alleles. Best parent heterosis, partial dominance, and negative nonadditivity were all rare phenomena. Nonadditive inheritance was observed primarily in crosses involving at least one very poor performing parent, most frequently of the West African population, and when molecularly dissected, loss-of-function alleles were identified as the underlying cause. These findings provide support for that population-specific loss-of-function mutations do have a strong impact on genotype-phenotype maps and underscores the role of neutral genetic drift as a driver for trait variation within species. PMID- 22319170 TI - Evolutionary conservation of histone modifications in mammals. AB - Histone modification is an important mechanism of gene regulation in eukaryotes. Why many histone modifications can be stably maintained in the midst of genetic and environmental changes is a fundamental question in evolutionary biology. We obtained genome-wide profiles of three histone marks, H3 lysine 4 tri-methylation (H3K4me3), H3 lysine 4 mono-methylation (H3K4me1), and H3 lysine 27 acetylation (H3K27ac), for several cell types from human and mouse. We identified histone modifications that were stable among different cell types in human and histone modifications that were evolutionarily conserved between mouse and human in the same cell type. We found that histone modifications that were stable among cell types were also likely to be conserved between species. This trend was consistently observed in promoter, intronic, and intergenic regions for all of the histone marks tested. Importantly, the trend was observed regardless of the expression breadth of the nearby gene, indicating that slow evolution of housekeeping genes was not the major reason for the correlation. These regions showed distinct genetic and epigenetic properties, such as clustered transcription factor binding sites (TFBSs), high GC content, and CTCF binding at flanking sides. Based on our observations, we proposed that TFBS clustering in or near a histone modification plays a significant role in stabilizing and conserving the histone modification because TFBS clustering promotes TFBS conservation, which in turn promotes histone modification conservation. In summary, the results of this study support the view that in mammalian genomes a common mechanism maintains histone modifications against both genetic and environmental (cellular) changes. PMID- 22319171 TI - An ancestral miR-1304 allele present in Neanderthals regulates genes involved in enamel formation and could explain dental differences with modern humans. AB - Genetic changes in regulatory elements are likely to result in phenotypic effects that might explain population-specific as well as species-specific traits. MicroRNAs (miRNAs) are posttranscriptional repressors involved in the control of almost every biological process. These small noncoding RNAs are present in various phylogenetic groups, and a large number of them remain highly conserved at the sequence level. MicroRNA-mediated regulation depends on perfect matching between the seven nucleotides of its seed region and the target sequence usually located at the 3' untranslated region of the regulated gene. Hence, even single changes in seed regions are predicted to be deleterious as they may affect miRNA target specificity. In accordance to this, purifying selection has strongly acted on these regions. Comparison between the genomes of present-day humans from various populations, Neanderthal, and other nonhuman primates showed an miRNA, miR-1304, that carries a polymorphism on its seed region. The ancestral allele is found in Neanderthal, nonhuman primates, at low frequency (~5%) in modern Asian populations and rarely in Africans. Using miRNA target site prediction algorithms, we found that the derived allele increases the number of putative target genes for the derived miRNA more than ten-fold, indicating an important functional evolution for miR-1304. Analysis of the predicted targets for derived miR-1304 indicates an association with behavior and nervous system development and function. Two of the predicted target genes for the ancestral miR-1304 allele are important genes for teeth formation, enamelin, and amelotin. MicroRNA overexpression experiments using a luciferase-based assay showed that the ancestral version of miR-1304 reduces the enamelin- and amelotin-associated reporter gene expression by 50%, whereas the derived miR-1304 does not have any effect. Deletion of the corresponding target sites for miR-1304 in these dental genes avoided their repression, which further supports their regulation by the ancestral miR-1304. Morphological studies described several differences in the dentition of Neanderthals and present-day humans like slower dentition timing and thicker enamel for present-day humans. The observed miR-1304-mediated regulation of enamelin and amelotin could at least partially underlie these differences between the two Homo species as well as other still-unraveled phenotypic differences among modern human populations. PMID- 22319172 TI - The functional A allele was resurrected via recombination in the human ABO blood group gene. AB - Functional A and B alleles are distinguished at two critical sites in exon 7 of the human ABO blood group gene. The most frequent nonfunctional O alleles have one-base deletion in exon 6 producing a frameshift, and it has the A type signature in two critical sites in exon 7. Previous studies indicated that B and O alleles were derived from A allele in human lineage. In this study, we conducted a phylogenetic network analysis using six representative haplotypes: A101, A201, B101, O01, O02, and O09. The result indicated that the A allele, possibly once extinct in the human lineage a long time ago, was resurrected by a recombination between B and O alleles less than 300,000 years ago. PMID- 22319173 TI - Coalescent-based analysis distinguishes between allo- and autopolyploid origin in Shepherd's Purse (Capsella bursa-pastoris). AB - Polyploidization plays an important role in plant speciation. The most recent estimates report that up to 15% of angiosperm speciation events and 31% in ferns are accompanied by changes in ploidy level. Polyploids can arise either through autopolyploidy, when the sets of chromosomes originate from a single species, or through allopolyploidy, when they originate from different species. In this study, we used two different coalescent-based methods to determine the date and mode of the polyploidization event that led to the tetraploid cosmopolitan weed, Capsella bursa-pastoris. We sampled 78 C. bursa-pastoris accessions, and 53 and 43 accessions from the only two other members of this genus, C. grandiflora and C. rubella, respectively, and sequenced these accessions at 14 unlinked nuclear loci with locus-specific primers in order to be able to distinguish the two homeologues in the tetraploid. A large fraction of fixed differences between homeologous genes in C. bursa-pastoris are segregating as polymorphisms in C. grandiflora, consistent with an autopolyploid origin followed by disomic inheritance. To test this, we first estimated the demographic parameters of an isolation-with-migration model in a pairwise fashion between C. grandiflora and both genomes of C. bursa-pastoris and used these parameters in coalescent simulations to test the mode of origin of C. bursa-pastoris. Second, we used Approximate Bayesian Computation to compare an allopolyploid and an autopolyploid model. Both analyses led to the conclusion that C. bursa-pastoris originated less than 1 Ma by doubling of the C. grandiflora genome. PMID- 22319174 TI - Concatenation and concordance in the reconstruction of mouse lemur phylogeny: an empirical demonstration of the effect of allele sampling in phylogenetics. AB - The systematics and speciation literature is rich with discussion relating to the potential for gene tree/species tree discordance. Numerous mechanisms have been proposed to generate discordance, including differential selection, long-branch attraction, gene duplication, genetic introgression, and/or incomplete lineage sorting. For speciose clades in which divergence has occurred recently and rapidly, recovering the true species tree can be particularly problematic due to incomplete lineage sorting. Unfortunately, the availability of multilocus or "phylogenomic" data sets does not simply solve the problem, particularly when the data are analyzed with standard concatenation techniques. In our study, we conduct a phylogenetic study for a nearly complete species sample of the dwarf and mouse lemur clade, Cheirogaleidae. Mouse lemurs (genus, Microcebus) have been intensively studied over the past decade for reasons relating to their high level of cryptic species diversity, and although there has been emerging consensus regarding the evolutionary diversity contained within the genus, there is no agreement as to the inter-specific relationships within the group. We attempt to resolve cheirogaleid phylogeny, focusing especially on the mouse lemurs, by employing a large multilocus data set. We compare the results of Bayesian concordance methods with those of standard gene concatenation, finding that though concatenation yields the strongest results as measured by statistical support, these results are found to be highly misleading. By employing an approach where individual alleles are treated as operational taxonomic units, we show that phylogenetic results are substantially influenced by the selection of alleles in the concatenation process. PMID- 22319175 TI - Informatics research to enable clinically relevant, personalized genomic medicine. PMID- 22319176 TI - Importance of multi-modal approaches to effectively identify cataract cases from electronic health records. AB - OBJECTIVE: There is increasing interest in using electronic health records (EHRs) to identify subjects for genomic association studies, due in part to the availability of large amounts of clinical data and the expected cost efficiencies of subject identification. We describe the construction and validation of an EHR based algorithm to identify subjects with age-related cataracts. MATERIALS AND METHODS: We used a multi-modal strategy consisting of structured database querying, natural language processing on free-text documents, and optical character recognition on scanned clinical images to identify cataract subjects and related cataract attributes. Extensive validation on 3657 subjects compared the multi-modal results to manual chart review. The algorithm was also implemented at participating electronic MEdical Records and GEnomics (eMERGE) institutions. RESULTS: An EHR-based cataract phenotyping algorithm was successfully developed and validated, resulting in positive predictive values (PPVs) >95%. The multi-modal approach increased the identification of cataract subject attributes by a factor of three compared to single-mode approaches while maintaining high PPV. Components of the cataract algorithm were successfully deployed at three other institutions with similar accuracy. DISCUSSION: A multi modal strategy incorporating optical character recognition and natural language processing may increase the number of cases identified while maintaining similar PPVs. Such algorithms, however, require that the needed information be embedded within clinical documents. CONCLUSION: We have demonstrated that algorithms to identify and characterize cataracts can be developed utilizing data collected via the EHR. These algorithms provide a high level of accuracy even when implemented across multiple EHRs and institutional boundaries. PMID- 22319177 TI - Incorporating molecular and functional context into the analysis and prioritization of human variants associated with cancer. AB - BACKGROUND AND OBJECTIVE: With recent breakthroughs in high-throughput sequencing, identifying deleterious mutations is one of the key challenges for personalized medicine. At the gene and protein level, it has proven difficult to determine the impact of previously unknown variants. A statistical method has been developed to assess the significance of disease mutation clusters on protein domains by incorporating domain functional annotations to assist in the functional characterization of novel variants. METHODS: Disease mutations aggregated from multiple databases were mapped to domains, and were classified as either cancer- or non-cancer-related. The statistical method for identifying significantly disease-associated domain positions was applied to both sets of mutations and to randomly generated mutation sets for comparison. To leverage the known function of protein domain regions, the method optionally distributes significant scores to associated functional feature positions. RESULTS: Most disease mutations are localized within protein domains and display a tendency to cluster at individual domain positions. The method identified significant disease mutation hotspots in both the cancer and non-cancer datasets. The domain significance scores (DS-scores) for cancer form a bimodal distribution with hotspots in oncogenes forming a second peak at higher DS-scores than non-cancer, and hotspots in tumor suppressors have scores more similar to non-cancers. In addition, on an independent mutation benchmarking set, the DS-score method identified mutations known to alter protein function with very high precision. CONCLUSION: By aggregating mutations with known disease association at the domain level, the method was able to discover domain positions enriched with multiple occurrences of deleterious mutations while incorporating relevant functional annotations. The method can be incorporated into translational bioinformatics tools to characterize rare and novel variants within large-scale sequencing studies. PMID- 22319178 TI - Multiplex meta-analysis of RNA expression to identify genes with variants associated with immune dysfunction. AB - OBJECTIVE: We demonstrate a genome-wide method for the integration of many studies of gene expression of phenotypically similar disease processes, a method of multiplex meta-analysis. We use immune dysfunction as an example disease process. DESIGN: We use a heterogeneous collection of datasets across human and mice samples from a range of tissues and different forms of immunodeficiency. We developed a method integrating Tibshirani's modified t-test (SAM) is used to interrogate differential expression within a study and Fisher's method for omnibus meta-analysis to identify differentially expressed genes across studies. The ability of this overall gene expression profile to prioritize disease associated genes is evaluated by comparing against the results of a recent genome wide association study for common variable immunodeficiency (CVID). RESULTS: Our approach is able to prioritize genes associated with immunodeficiency in general (area under the ROC curve = 0.713) and CVID in particular (area under the ROC curve = 0.643). CONCLUSIONS: This approach may be used to investigate a larger range of failures of the immune system. Our method may be extended to other disease processes, using RNA levels to prioritize genes likely to contain disease associated DNA variants. PMID- 22319179 TI - A comparison of cataloged variation between International HapMap Consortium and 1000 Genomes Project data. AB - BACKGROUND: Since publication of the human genome in 2003, geneticists have been interested in risk variant associations to resolve the etiology of traits and complex diseases. The International HapMap Consortium undertook an effort to catalog all common variation across the genome (variants with a minor allele frequency (MAF) of at least 5% in one or more ethnic groups). HapMap along with advances in genotyping technology led to genome-wide association studies which have identified common variants associated with many traits and diseases. In 2008 the 1000 Genomes Project aimed to sequence 2500 individuals and identify rare variants and 99% of variants with a MAF of <1%. METHODS: To determine whether the 1000 Genomes Project includes all the variants in HapMap, we examined the overlap between single nucleotide polymorphisms (SNPs) genotyped in the two resources using merged phase II/III HapMap data and low coverage pilot data from 1000 Genomes. RESULTS: Comparison of the two data sets showed that approximately 72% of HapMap SNPs were also found in 1000 Genomes Project pilot data. After filtering out HapMap variants with a MAF of <5% (separately for each population), 99% of HapMap SNPs were found in 1000 Genomes data. CONCLUSIONS: Not all variants cataloged in HapMap are also cataloged in 1000 Genomes. This could affect decisions about which resource to use for SNP queries, rare variant validation, or imputation. Both the HapMap and 1000 Genomes Project databases are useful resources for human genetics, but it is important to understand the assumptions made and filtering strategies employed by these projects. PMID- 22319180 TI - Translating Mendelian and complex inheritance of Alzheimer's disease genes for predicting unique personal genome variants. AB - OBJECTIVE: Although trait-associated genes identified as complex versus single gene inheritance differ substantially in odds ratio, the authors nonetheless posit that their mechanistic concordance can reveal fundamental properties of the genetic architecture, allowing the automated interpretation of unique polymorphisms within a personal genome. MATERIALS AND METHODS: An analytical method, SPADE-gen, spanning three biological scales was developed to demonstrate the mechanistic concordance between Mendelian and complex inheritance of Alzheimer's disease (AD) genes: biological functions (BP), protein interaction modeling, and protein domain implicated in the disease-associated polymorphism. RESULTS: Among Gene Ontology (GO) biological processes (BP) enriched at a false detection rate <5% in 15 AD genes of Mendelian inheritance (Online Mendelian Inheritance in Man) and independently in those of complex inheritance (25 host genes of intragenic AD single-nucleotide polymorphisms confirmed in genome-wide association studies), 16 overlapped (empirical p=0.007) and 45 were similar (empirical p<0.009; information theory). SPAN network modeling extended the canonical pathway of AD (KEGG) with 26 new protein interactions (empirical p<0.0001). DISCUSSION: The study prioritized new AD-associated biological mechanisms and focused the analysis on previously unreported interactions associated with the biological processes of polymorphisms that affect specific protein domains within characterized AD genes and their direct interactors using (1) concordant GO-BP and (2) domain interactions within STRING protein-protein interactions corresponding to the genomic location of the AD polymorphism (eg, EPHA1, APOE, and CD2AP). CONCLUSION: These results are in line with unique-event polymorphism theory, indicating how disease-associated polymorphisms of Mendelian or complex inheritance relate genetically to those observed as 'unique personal variants'. They also provide insight for identifying novel targets, for repositioning drugs, and for personal therapeutics. PMID- 22319182 TI - Re: "Asthma and caries: a systematic review and meta-analysis". PMID- 22319183 TI - Re: "Asthma and caries: a systematic review and meta-analysis". PMID- 22319184 TI - Medical biography: the philatelic record. PMID- 22319185 TI - The other Dr Hooker: William Dawson Hooker (1816-40). AB - William Hooker and his son Joseph were famous as botanists and as the creators of the Royal Botanic Gardens in Kew. Joseph was famous also as the friend and mentor of Charles Darwin. But there was another brother, a little older than Joseph, also a doctor and naturalist. He went to Jamaica in the interests of his health and soon died there of yellow fever. His life was short and tragic with a medical conundrum at its end but its story also illustrates many of the beliefs and concerns that preoccupied doctors in this early Victorian era. It also illustrates the close relationship between medicine and botany that prevailed then. PMID- 22319186 TI - Henry Ingersoll Bowditch (1808-82): American physician, public health advocate and social reformer. AB - Henry Ingersoll Bowditch, a Bostonian physician from the mid-19th century, lived a passionate life full of commitment and devotion to various noble causes--he was a champion of public health, an advocate for inclusion of women in medicine and a staunch abolitionist, all unpopular social perspectives at that time in medical and political history. Seemingly difficult personality traits including his stubbornness and moralistic outlook were likely 'adaptive' as he confronted the political reality of major institutional change. His interest in statistical trends and environmental influences and his inductive reasoning led to a deeper understanding of consumption (tuberculosis), the widespread diagnostic use of the stethoscope and thoracocentesis. PMID- 22319187 TI - Father of the modern hip replacement: Professor Sir John Charnley (1911-82). AB - Professor Sir John Charnley was a British orthopaedic surgeon, inventor and skilled craftsman. He is best known for his development of the first truly successful operation for total arthroplasty of the hip, the low-friction arthroplasty. As well as publishing significant works on closed fracture management and compression arthrodesis, he can also be accredited with pioneering work in the development of clean-air operating conditions and body-exhaust suits. PMID- 22319188 TI - Philibert Joseph Roux (1780-1854). AB - Philibert Joseph Roux (1780-1854), a French surgeon, was a student and friend of Marie Xavier Francois Bichat, the father of modern pathology and histology. He was assigned as a surgeon to the Hopital Beaujon (1806), the Hopital de la Charite (1810) and to Hotel-Dieu de Paris (1835), where he succeeded to Guillaume Dupuyrten, a French anatomist, as a Chief Surgeon. Roux is best known for having performed the surgical repair of a cleft palate and for having been the first surgeon to stitch a ruptured female perineum. His contribution to surgery has also included the publication of Quarante annees de pratique chirurgicale. Roux was awarded the grade of Chevalier of the National Order of the legion of Honor and that of Officer. He also served as a President of the Academy of Sciences. He died of a stroke on 3 March 1854. PMID- 22319189 TI - Johns Hopkins Hospital notables portrayed on philatelic material. AB - The philatelic medium is an extensive repository of the portraits of doctors of many nations. Using an electronic matching system to identify links between the lists of alumni and faculties register of Johns Hopkins Hospital in Baltimore and that of three stamp catalogues, 14 notable persons have been identified in the philatelic record. The Johns Hopkins Hospital was established in Baltimore in 1889 and instituted the revolutionary concept of combining patient care with research and teaching. Its founder Johns Hopkins (1795-1873) and 13 among alumni and faculties have been portrayed on postage stamps and first day covers of USA, Canada, Antigua, Barbuda, Palau, Maldives, Canada and Sweden. Five of them--du Vigneaud (1901-78), Smith (b. 1931), Nathans (1928-99), Hubel (b. 1926) and Wiesel (b. 1924)--were awarded the Nobel Prize for Medicine or Physiology. By means of the philatelic medium, portraits of Hopkins scientists and doctors, including Sir William Osler (1849-1919) and Dr Virgina Apgar (1909-74), are distributed in their many tens of thousands on envelopes sent not only to recipients in the USA but to the wider world. PMID- 22319190 TI - Wanda Ossowska (1912-2001) and Stanislawa Leszczynska (1896-1974): Polish nurses working under Nazi occupation. AB - Poland was invaded by Nazi Germany on 1 September 1939 and World War II began on 3 September. Polish nurses have their place in this difficult history. In the first months of occupation, nurses focused on caring for wounded soldiers. In order to protect them from prisoner-of-war camps and execution, nurses sought safe havens for the wounded in private homes and transported them there. After their regular jobs, the nurses visited them, changed their dressings and provided them with civilian clothes so that soldiers could eventually escape. This paper describes the work of two of these nurses, Wanda Ossowska and Stanislawa Leszczynska. The first three authors (BD, SH, AJS) were nurses in Poland at that time and they present some of the information in this paper as primary source data. PMID- 22319191 TI - Medicine in Dr Samuel Johnson's Dictionary of the English Language. AB - When compiling the Dictionary of the English Language, Johnson read and annotated over two hundred thousand passages from innumerable English authors of various disciplines across four centuries. Most of the literary anecdotes came from Shakespeare, Milton, Dryden and Pope. The medical and scientific anecdotes came from 31 scientists, physicians, pharmacologists and surgeons. This reflects Johnson's admiration for science and its benefit to the public. He told Boswell, 'Why Sir, if you have but one book with you upon a journey let it be a book of science. When you read through a book of entertainment, you know it, and it can do no more for you, but a book of science is inexhaustible'. PMID- 22319192 TI - Arthur Neve (1859-1919) and a Mission Hospital in Srinagar, Kashmir. AB - Mark Harrison has said that hospitals occupy a central place within health-care systems, not only on account of their curative functions but also as centres of teaching and research. The indigenous system of medicine practised by Hakims in Kashmir is the Unani. The Mission Hospital in Srinagar, Kashmir became the most important hospital attracting patients, not only within Kashmir but also in the surrounding countries and not only because of the curative facilities provided at the hospital but also because of the humane approach of its physicians, outstanding among them being Arthur Neve. The patients represented every class of society. Patients come from villages scattered throughout Kashmir and the Plains of India, and a few from Tibet, Afghanistan, Yarkand and Khostan. According to Neve, in 1912 there were 23,642 new outpatients and 1979 inpatients. Physical, socio-cultural and political conditions hinder access to the Mission Hospital. Neve's younger brother Ernest F Neve (1861-1946) made significant contributions when an earthquake struck and during cholera outbreaks in Kashmir at the end of the 19th century. PMID- 22319193 TI - William Cadogan (1711-97): colossus of child care. PMID- 22319194 TI - Ronald Ross' opposition to Battista Grassi's malaria research. PMID- 22319196 TI - Species comparison and pharmacological characterization of human, monkey, rat, and mouse TRPA1 channels. AB - The transient receptor potential ankyrin-1 (TRPA1) channel has emerged as an attractive target for development of analgesic and anti-inflammatory drugs. However, drug discovery efforts targeting TRPA1 have been hampered by differences between human and rodent species. Many compounds have been identified to have antagonist activity at human TRPA1 (hTRPA1), but when tested at rat TRPA1 (rTRPA1) and mouse TRPA1 (mTRPA1), they show reduced potency as antagonists, no effect, or agonist activity. These compounds are excluded from further drug development because they cannot be tested in preclinical studies using conventional rat/mouse models. To broaden our understanding of species-specific differences, we cloned and functionally characterized rhesus monkey TRPA1 (rhTRPA1) and compared its pharmacological profile to hTRPA1, rTRPA1, and mTRPA1 channels. The functional activities of a diverse group of TRPA1 ligands (both reactive and nonreactive) were determined in a fluorescent Ca2+ influx assay, using transiently transfected human embryonic kidney 293-F cells. 4-Methyl-N [2,2,2-trichloro-1-(4-nitro-phenylsulfanyl)-ethyl]-benzamide, menthol, and caffeine displayed species-specific differential pharmacology at TRPA1. The pharmacological profile of the rhTRPA1 channel was found to be similar to the hTRPA1 channel. In contrast, the rTRPA1 and mTRPA1 channels closely resembled each other but were pharmacologically distinct from either hTRPA1 or rhTRPA1 channels. Our findings reveal that TRPA1 function differs between primate and rodent species and suggest that rhesus monkey could serve as a surrogate species for humans in preclinical studies. PMID- 22319197 TI - Effects of the GABAB receptor-positive modulators CGP7930 and rac-BHFF in baclofen- and gamma-hydroxybutyrate-discriminating pigeons. AB - In vivo effects of GABA(B) receptor-positive modulators suggest them to have therapeutic potential to treat central nervous system disorders such as anxiety and drug abuse. Although these effects are thought to be mediated by positive modulation of GABA(B) receptors, such modulation has been examined primarily in vitro. This study further examined the in vivo properties of the GABA(B) receptor positive modulators 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl) phenol (CGP7930) and (R,S)-5,7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2 one (rac-BHFF). In pigeons discriminating baclofen from saline, gamma hydroxybutyrate (GHB) produced 100% baclofen-appropriate responding, and the GABA(B) antagonist 3-aminopropyl(dimethoxymethyl) phosphinic acid (CGP35348) blocked the effects of both drugs. CGP7930 and rac-BHFF produced at most 41 and 74% baclofen-appropriate responding, respectively, and enhanced the discriminative stimulus effects of baclofen, but not of GHB. In pigeons discriminating GHB from saline, CGP7930 and rac-BHFF produced at most 1 and 49% GHB-appropriate responding, respectively, and enhanced the effects of baclofen, but not of GHB. Enhancement of the discriminative stimulus effects of baclofen by rac-BHFF and CGP7930 is further evidence of their effectiveness as GABA(B) receptor-positive modulators in vivo. Furthermore, lack of complete substitution of the positive modulators rac-BHFF and CGP7930 for baclofen and GHB suggests that their discriminative stimulus effects differ from those of GABA(B) receptor agonists. Finally, together with converging evidence that the GABA(B) receptor populations mediating the effects of baclofen and GHB are not identical, the present findings suggest that these populations differ in their susceptibility to positive modulatory effects. Such differences could allow for more selective therapeutic targeting of the GABA(B) system. PMID- 22319198 TI - Complement activation in acetaminophen-induced liver injury in mice. AB - Overdose with acetaminophen (APAP) results in acute liver failure in humans and experimental animals. Complement comprises more than 30 proteins that can participate in tissue injury and/or repair, but the role of complement activation in APAP-induced hepatotoxicity has not been evaluated. Treatment of male, C57BL6J mice with APAP (200-400 mg/kg) resulted in liver injury as evidenced by increased activity of alanine aminotransferase (ALT) in plasma and hepatocellular necrosis. Plasma concentration of the complement component C3 was significantly reduced 6 h after treatment with APAP, indicating complement activation, and C3b (detected by immunostaining) accumulated in the centrilobular areas of liver lobules. Pretreatment with cobra venom factor (CVF; 15 U/mouse) to deplete complement components abolished APAP-mediated C3b accumulation, and this was accompanied by reductions in plasma ALT activity, hepatocellular necrosis, hepatic neutrophil accumulation, and expression of inflammatory genes (interleukin-6, interleukin 10, and plasminogen activation inhibitor-1) at 24 h after APAP treatment. Loss of hepatocellular GSH was similar in APAP-treated mice pretreated with either saline or CVF, suggesting that CVF pretreatment did not affect APAP bioactivation. Mice with a genetic deficiency in C3 had reduced ALT activity 6 and 12 h after APAP administration compared with wild-type animals. These results reveal a key role for complement activation in hepatic inflammation and progression of injury during the pathogenesis of APAP-induced hepatotoxicity. PMID- 22319199 TI - CEP-32496: a novel orally active BRAF(V600E) inhibitor with selective cellular and in vivo antitumor activity. AB - Mutations in the BRAF gene have been identified in approximately 7% of cancers, including 60% to 70% of melanomas, 29% to 83% of papillary thyroid carcinomas, 4% to 16% colorectal cancers, and a lesser extent in serous ovarian and non-small cell lung cancers. The V600E mutation is found in the vast majority of cases and is an activating mutation, conferring transforming and immortalization potential to cells. CEP-32496 is a potent BRAF inhibitor in an in vitro binding assay for mutated BRAF(V600E) (K(d) BRAF(V600E) = 14 nmol/L) and in a mitogen-activated protein (MAP)/extracellular signal-regulated (ER) kinase (MEK) phosphorylation (pMEK) inhibition assay in human melanoma (A375) and colorectal cancer (Colo-205) cell lines (IC(50) = 78 and 60 nmol/L). In vitro, CEP-32496 has multikinase binding activity at other cancer targets of interest; however, it exhibits selective cellular cytotoxicity for BRAF(V600E) versus wild-type cells. CEP-32496 is orally bioavailable in multiple preclinical species (>95% in rats, dogs, and monkeys) and has single oral dose pharmacodynamic inhibition (10-55 mg/kg) of both pMEK and pERK in BRAF(V600E) colon carcinoma xenografts in nude mice. Sustained tumor stasis and regressions are observed with oral administration (30 100 mg/kg twice daily) against BRAF(V600E) melanoma and colon carcinoma xenografts, with no adverse effects. Little or no epithelial hyperplasia was observed in rodents and primates with prolonged oral administration and sustained exposure. CEP-32496 benchmarks favorably with respect to other kinase inhibitors, including RAF-265 (phase I), sorafenib, (approved), and vemurafenib (PLX4032/RG7204, approved). CEP-32496 represents a novel and pharmacologically active BRAF inhibitor with a favorable side effect profile currently in clinical development. PMID- 22319200 TI - Serine-305 phosphorylation modulates estrogen receptor alpha binding to a coregulator peptide array, with potential application in predicting responses to tamoxifen. AB - With current techniques, it remains a challenge to assess coregulator binding of nuclear receptors, for example, the estrogen receptor alpha (ERalpha). ERalpha is critical in many breast tumors and is inhibited by antiestrogens such as tamoxifen in cancer therapy. ERalpha is also modified by acetylation and phosphorylation that affect responses to the antiestrogens as well as interactions with coregulators. Phosphorylation of ERalpha at Ser305 is one of the mechanisms causing tamoxifen resistance. Detection of resistance in patient samples would greatly facilitate clinical decisions on treatment, in which such patients would receive other treatments such as aromatase inhibitors or fulvestrant. Here we describe a coregulator peptide array that can be used for high-throughput analysis of full-length estrogen receptor binding. The peptide chip can detect ERalpha binding in cell and tumor lysates. We show that ERalpha phosphorylated at Ser305 associates stronger to various coregulator peptides on the chip. This implies that ERalphaSer305 phosphorylation increases estrogen receptor function. As this is also detected in a breast tumor sample of a tamoxifen-insensitive patient, the peptide array, as described here, may be applicable to detect tamoxifen resistance in breast tumor samples at an early stage of disease and contribute to personalized medicine. PMID- 22319201 TI - NMS-P937, an orally available, specific small-molecule polo-like kinase 1 inhibitor with antitumor activity in solid and hematologic malignancies. AB - Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase considered to be the master player of cell-cycle regulation during mitosis. It is indeed involved in centrosome maturation, bipolar spindle formation, chromosome separation, and cytokinesis. PLK1 is overexpressed in a variety of human tumors and its overexpression often correlates with poor prognosis. Although five different PLKs are described in humans, depletion or inhibition of kinase activity of PLK1 is sufficient to induce cell-cycle arrest and apoptosis in cancer cell lines and in xenograft tumor models. NMS-P937 is a novel, orally available PLK1-specific inhibitor. The compound shows high potency in proliferation assays having low nanomolar activity on a large number of cell lines, both from solid and hematologic tumors. NMS-P937 potently causes a mitotic cell-cycle arrest followed by apoptosis in cancer cell lines and inhibits xenograft tumor growth with clear PLK1-related mechanism of action at well-tolerated doses in mice after oral administration. In addition, NMS-P937 shows potential for combination in clinical settings with approved cytotoxic drugs, causing tumor regression in HT29 human colon adenocarcinoma xenografts upon combination with irinotecan and prolonged survival of animals in a disseminated model of acute myelogenous leukemia in combination with cytarabine. NMS-P937, with its favorable pharmacologic parameters, good oral bioavailability in rodent and nonrodent species, and proven antitumor activity in different preclinical models using a variety of dosing regimens, potentially provides a high degree of flexibility in dosing schedules and warrants investigation in clinical settings. PMID- 22319202 TI - Nanobodies targeting the hepatocyte growth factor: potential new drugs for molecular cancer therapy. AB - Hepatocyte growth factor (HGF) and its receptor c-Met are associated with increased aggressiveness of tumors and poor prognostic outcome of patients with cancer. Here, we report the development and characterization of therapeutic anti HGF (alphaHGF)-Nanobodies and their potential for positron emission tomographic (PET) imaging to assess HGF expression in vivo. Two alphaHGF-Nanobodies designated 1E2 and 6E10 were identified, characterized, and molecularly fused to an albumin-binding Nanobody unit (Alb8) to obtain serum half-life extension. The resulting Nanobody formats were radiolabeled with the positron emitter zirconium 89 ((89)Zr, t(1/2;) = 78 hours), administered to nude mice bearing U87 MG glioblastoma xenografts, and their biodistribution was assessed. In addition, their therapeutic effect was evaluated in the same animal model at doses of 10, 30, or 100 MUg per mouse. The (89)Zr-Nanobodies showed similar biodistribution with selective tumor targeting. For example, 1E2-Alb8 showed decreased blood levels of 12.6%ID/g +/- 0.6%ID/g, 7.2%ID/g +/- 1.0%ID/g, 3.4%ID/g +/- 0.3%ID/g, and 0.3%ID/g +/- 0.1%ID/g at 1, 2, 3, and 7 days after injection, whereas tumor uptake levels remained relatively stable at these time points: 7.8%ID/g +/- 1.1%ID/g, 8.9%ID/g +/- 1.0%ID/g, 8.7%ID/g +/- 1.5%ID/g, and 7.2%ID/g +/-1.6%ID/g. Uptake in normal tissues was lower than in tumor, except for kidneys. In a therapy study, all Nanobody-treated mice showed tumor growth delay compared with the control saline group. In the 100-MUg group, four of six mice were cured after treatment with 1E2-Alb8 and 73 days follow-up, and three of six mice when treated with 6E10-Alb8. These results provide evidence that Nanobodies 1E2-Alb8 and 6E10 Alb8 have potential for therapy and PET imaging of HGF-expressing tumors. PMID- 22319203 TI - Honokiol in combination with radiation targets notch signaling to inhibit colon cancer stem cells. AB - Cancer stem cells are implicated in resistance to ionizing radiation (IR) and chemotherapy. Honokiol, a biphenolic compound has been used in traditional Chinese medicine for treating various ailments. In this study, we determined the ability of honokiol to enhance the sensitivity of colon cancer stem cells to IR. The combination of honokiol and IR suppressed proliferation and colony formation while inducing apoptosis of colon cancer cells in culture. There were also reduced numbers and size of spheroids, which was coupled with reduced expression of cancer stem cell marker protein DCLK1. Flow cytometry studies confirmed that the honokiol-IR combination reduced the number of DCLK1+ cells. In addition, there were reduced levels of activated Notch-1, its ligand Jagged-1, and the downstream target gene Hes-1. Furthermore, expression of components of the Notch 1 activating gamma-secretase complex, presenilin 1, nicastrin, Pen2, and APH-1 was also suppressed. On the other hand, the honokiol effects were mitigated when the Notch intracellular domain was expressed. To determine the effect of honokiol IR combination on tumor growth in vivo, nude mice tumor xenografts were administered honokiol intraperitoneally and exposed to IR. The honokiol-IR combination significantly inhibited tumor xenograft growth. In addition, there were reduced levels of DCLK1 and the Notch signaling-related proteins in the xenograft tissues. Together, these data suggest that honokiol is a potent inhibitor of colon cancer growth that targets the stem cells by inhibiting the gamma-secretase complex and the Notch signaling pathway. These studies warrant further clinical evaluation for the combination of honokiol and IR for treating colon cancers. PMID- 22319204 TI - SKLB1206, a novel orally available multikinase inhibitor targeting EGFR activating and T790M mutants, ErbB2, ErbB4, and VEGFR2, displays potent antitumor activity both in vitro and in vivo. AB - Anti-epidermal growth factor receptor (EGFR) treatment has been successfully applied in clinical cancer therapy. However, the clinical efficacy of first generation reversible EGFR inhibitors, such as gefitinib and erlotinib, is limited by the development of drug-resistant mutations, including the gatekeeper T790M mutation and upregulation of alternative signaling pathways. Second generation irreversible EGFR inhibitors that were designed to overcome the drug resistance due to the T790M mutation have thus far had limited success. Here, we report a novel reversible EGFR inhibitor, SKLB1206, which has potent activity against EGFR with gefitinib-sensitive and -resistant (T790M) mutations. In addition, SKLB1206 has also considerable inhibition potency against some other related oncokinases, including ErbB2, ErbB4, and VEGF receptor 2 (VEGFR2). SKLB1206 exhibited highly antiproliferative activity against a range of EGFR mutant cell lines, including gefitinib-sensitive and -resistant cell lines, and EGFR or ErbB2-overexpressing cell lines. SKLB1206 also showed a potent antiangiogenesis effect in vitro, in a zebrafish embryonic angiogenesis assay, and in an alginate-encapsulate tumor cell assay. In vivo, oral administration of SKLB1206 showed complete tumor regression in gefitinib-sensitive HCC827 and PC-9 xenograft models and showed a considerable antitumor effect on the gefitinib resistant H1975 model as well as other EGFR/ErbB2-overexpressing or -dependent tumor models including A431, LoVo, and N87 established in athymic mice. SKLB1206 also showed a very good oral bioavailability (50.1%). Collectively, these preclinical evaluations may support clinical development of SKLB1206 for cancers with EGFR-activating/resistance mutations or EGFR/ErbB2 overexpressed. PMID- 22319205 TI - Nuclear factor-kappaB mediates placental growth factor induced pro-labour mediators in human placenta. AB - Prostaglandins, pro-inflammatory cytokines, extracellular matrix remodelling enzymes and nuclear factor-kappa B (NF-kappaB) are involved in the mechanisms of term and preterm parturition. Recent studies have reported an increase in angiogenesis-related genes during term and preterm labour, including placental growth factor (PLGF). In non-gestational tissues, PLGF induces inflammation via NF-kappaB. The aim of this study was to determine the effect of PLGF on the gene expression and release of pro-labour mediators in human placenta. Samples were obtained from normal pregnancies at the time of Caesarean section. Human placenta was incubated in the absence (basal control) or presence of a 10 ng/ml PLGF for 24 h. Inflammatory gene expression was analysed by quantitative RT-PCR, concentration of pro-inflammatory cytokines and prostaglandins was quantified by ELISA, and secretory matrix metalloproteinases (MMPs) activity by zymography. NF kappaB DNA-binding activity and IkappaB-alpha (inhibitor of NF-kappaB) protein degradation were analysed by ELISA and Western blotting, respectively. PLGF significantly increased interleukin (IL)-6 and IL-8 gene expression and secretion, cyclooxygenase-2 expression and resultant prostaglandin (PG) E(2) and PGF(2alpha) release, and MMP-9 gene expression and enzyme production. PLGF induced the degradation of IkappaB-alpha whilst increasing NF-kappaB p65 DNA binding activity. The PLGF-induced pro-labour responses were abrogated by co treatment with the NF-kappaB inhibitor BAY 11-7082. In summary, the pro inflammatory and pro-labour effects of PLGF in human placenta are mediated by NF kappaB. PMID- 22319206 TI - mRNA transcript diversity creates new opportunities for pharmacological intervention. AB - Most protein coding genes generate multiple RNA transcripts through alternative splicing, variable 3' and 5'UTRs, and RNA editing. Although drug design typically targets the main transcript, alternative transcripts can have profound physiological effects, encoding proteins with distinct functions or regulatory properties. Formation of these alternative transcripts is tissue-selective and context-dependent, creating opportunities for more effective and targeted therapies with reduced adverse effects. Moreover, genetic variation can tilt the balance of alternative versus constitutive transcripts or generate aberrant transcripts that contribute to disease risk. In addition, environmental factors and drugs modulate RNA splicing, affording new opportunities for the treatment of splicing disorders. For example, therapies targeting specific mRNA transcripts with splice-site-directed oligonucleotides that correct aberrant splicing are already in clinical trials for genetic disorders such as Duchenne muscular dystrophy. High-throughput sequencing technologies facilitate discovery of novel RNA transcripts and protein isoforms, applications ranging from neuromuscular disorders to cancer. Consideration of a gene's transcript diversity should become an integral part of drug design, development, and therapy. PMID- 22319207 TI - Quantitative variation in water-use efficiency across water regimes and its relationship with circadian, vegetative, reproductive, and leaf gas-exchange traits. AB - Drought limits light harvesting, resulting in lower plant growth and reproduction. One trait important for plant drought response is water-use efficiency (WUE). We investigated (1) how the joint genetic architecture of WUE, reproductive characters, and vegetative traits changed across drought and well watered conditions, (2) whether traits with distinct developmental bases (e.g. leaf gas exchange versus reproduction) differed in the environmental sensitivity of their genetic architecture, and (3) whether quantitative variation in circadian period was related to drought response in Brassica rapa. Overall, WUE increased in drought, primarily because stomatal conductance, and thus water loss, declined more than carbon fixation. Genotypes with the highest WUE in drought expressed the lowest WUE in well-watered conditions, and had the largest vegetative and floral organs in both treatments. Thus, large changes in WUE enabled some genotypes to approach vegetative and reproductive trait optima across environments. The genetic architecture differed for gas-exchange and vegetative traits across drought and well-watered conditions, but not for floral traits. Correlations between circadian and leaf gas-exchange traits were significant but did not vary across treatments, indicating that circadian period affects physiological function regardless of water availability. These results suggest that WUE is important for drought tolerance in Brassica rapa and that artificial selection for increased WUE in drought will not result in maladaptive expression of other traits that are correlated with WUE. PMID- 22319208 TI - Flap endonucleases pass 5'-flaps through a flexible arch using a disorder-thread order mechanism to confer specificity for free 5'-ends. AB - Flap endonucleases (FENs), essential for DNA replication and repair, recognize and remove RNA or DNA 5'-flaps. Related to FEN specificity for substrates with free 5'-ends, but controversial, is the role of the helical arch observed in varying conformations in substrate-free FEN structures. Conflicting models suggest either 5'-flaps thread through the arch, which when structured can only accommodate single-stranded (ss) DNA, or the arch acts as a clamp. Here we show that free 5'-termini are selected using a disorder-thread-order mechanism. Adding short duplexes to 5'-flaps or 3'-streptavidin does not markedly impair the FEN reaction. In contrast, reactions of 5'-streptavidin substrates are drastically slowed. However, when added to premixed FEN and 5'-biotinylated substrate, streptavidin is not inhibitory and complexes persist after challenge with unlabelled competitor substrate, regardless of flap length or the presence of a short duplex. Cross-linked flap duplexes that cannot thread through the structured arch react at modestly reduced rate, ruling out mechanisms involving resolution of secondary structure. Combined results explain how FEN avoids cutting template DNA between Okazaki fragments and link local FEN folding to catalysis and specificity: the arch is disordered when flaps are threaded to confer specificity for free 5'-ends, with subsequent ordering of the arch to catalyze hydrolysis. PMID- 22319209 TI - Analysis of MRE11's function in the 5'-->3' processing of DNA double-strand breaks. AB - The resection of DNA double-strand breaks (DSBs) into 3' single-strand tails is the initiating step of homology-dependent repair pathways. A key player in this process is the MRE11-RAD50-NBS1 complex, but its contribution to and mechanistic role in resection are not well understood. In this study, we took advantage of the Xenopus egg extract system to address these questions. We found that depletion of MRE11 caused a dramatic inhibition of 5'-resection, even for the first nucleotide at the 5'-end. Depletion of Xenopus CtIP also inhibited 5' strand resection, but this inhibition could be alleviated by excess MRN. Both MRE11 and CtIP could be bypassed by a DNA that carried a 3'-ss-tail. Finally, using purified proteins, we found that MRN could stimulate both the WRN-DNA2-RPA pathway and the EXO1 pathway of resection. These findings provide important insights into the function of MRE11 in 5'-strand resection. PMID- 22319210 TI - Genome-wide analyses reveal the extent of opportunistic STAT5 binding that does not yield transcriptional activation of neighboring genes. AB - Signal Transducers and Activators of Transcription (STAT) 5A/B regulate cytokine inducible genes upon binding to GAS motifs. It is not known what percentage of genes with GAS motifs bind to and are regulated by STAT5. Moreover, it is not clear whether genome-wide STAT5 binding is modulated by its concentration. To clarify these issues we established genome-wide STAT5 binding upon growth hormone (GH) stimulation of wild-type (WT) mouse embryonic fibroblasts (MEFs) and MEFs overexpressing STAT5A more than 20-fold. Upon GH stimulation, 23 827 and 111 939 STAT5A binding sites were detected in WT and STAT5A overexpressing MEFs, respectively. 13 278 and 71 561 peaks contained at least one GAS motif. 1586 and 8613 binding sites were located within 2.5 kb of promoter sequences, respectively. Stringent filtering revealed 78 genes in which the promoter/upstream region (-10 kb to +0.5 kb) was recognized by STAT5 both in WT and STAT5 overexpressing MEFs and 347 genes that bound STAT5 only in overexpressing cells. Genome-wide expression analyses identified that the majority of STAT5-bound genes was not under GH control. Up to 40% of STAT5-bound genes were not expressed. For the first time we demonstrate the magnitude of opportunistic genomic STAT5 binding that does not translate into transcriptional activation of neighboring genes. PMID- 22319211 TI - Ebp2 and Brx1 function cooperatively in 60S ribosomal subunit assembly in Saccharomyces cerevisiae. AB - The yeast protein Ebp2 is required for early steps in production of 60S ribosomal subunits. To search for cofactors with which Ebp2 functions, or substrates on which it acts, we screened for mutants that were synthetically lethal (sl) with the ebp2-14 mutation. Four different mutant alleles of the 60S ribosomal subunit assembly factor Brx1 were found. To investigate defects of the double mutant, we constructed strains conditional for the ebp2-14 brx1- synthetic lethal phenotype. These ebp2-14 brx1 mutants were defective in processing of 27S pre-rRNA and production of 60S subunits, under conditions where each single mutant was not. Ebp2 and Brx1 exhibit a strong two-hybrid interaction, which is eliminated by some combinations of brx1 and ebp2 mutations. In one such mutant, Ebp2 and Brx1 can still associate with pre-ribosomes, but subunit maturation is perturbed. Depletion of either Ebp2 or Brx1 revealed that Brx1 requires Ebp2 for its stable association with pre-ribosomes, but Ebp2 does not depend on the presence of Brx1 to enter pre-ribosomes. These results suggest that assembly of 60S ribosomal subunits requires cooperation of Ebp2 with Brx1, together with other molecules present in pre-ribosomes, potentially including several found in assembly subcomplexes with Brx1 and Ebp2. PMID- 22319212 TI - CUX1 transcription factor is required for optimal ATM/ATR-mediated responses to DNA damage. AB - The p110 Cut homeobox 1 (CUX1) transcription factor regulates genes involved in DNA replication and chromosome segregation. Using a genome-wide-approach, we now demonstrate that CUX1 also modulates the constitutive expression of DNA damage response genes, including ones encoding ATM and ATR, as well as proteins involved in DNA damage-induced activation of, and signaling through, these kinases. Consistently, RNAi knockdown or genetic inactivation of CUX1 reduced ATM/ATR expression and negatively impacted hallmark protective responses mediated by ATM and ATR following exposure to ionizing radiation (IR) and UV, respectively. Specifically, abrogation of CUX1 strongly reduced ATM autophosphorylation after IR, in turn causing substantial decreases in (i) levels of phospho-Chk2 and p53, (ii) gamma-H2AX and Rad51 DNA damage foci and (iii) the efficiency of DNA strand break repair. Similarly remarkable reductions in ATR-dependent responses, including phosphorylation of Chk1 and H2AX, were observed post-UV. Finally, multiple cell cycle checkpoints and clonogenic survival were compromised in CUX1 knockdown cells. Our results indicate that CUX1 regulates a transcriptional program that is necessary to mount an efficient response to mutagenic insult. Thus, CUX1 ensures not only the proper duplication and segregation of the genetic material, but also the preservation of its integrity. PMID- 22319213 TI - DNA polymerase zeta is required for proliferation of normal mammalian cells. AB - Unique among translesion synthesis (TLS) DNA polymerases, pol zeta is essential during embryogenesis. To determine whether pol zeta is necessary for proliferation of normal cells, primary mouse fibroblasts were established in which Rev3L could be conditionally inactivated by Cre recombinase. Cells were grown in 2% O(2) to prevent oxidative stress-induced senescence. Cells rapidly became senescent or apoptotic and ceased growth within 3-4 population doublings. Within one population doubling following Rev3L deletion, DNA double-strand breaks and chromatid aberrations were found in 30-50% of cells. These breaks were replication dependent, and found in G1 and G2 phase cells. Double-strand breaks were reduced when cells were treated with the reactive oxygen species scavenger N acetyl-cysteine, but this did not rescue the cell proliferation defect, indicating that several classes of endogenously formed DNA lesions require Rev3L for tolerance or repair. T-antigen immortalization of cells allowed cell growth. In summary, even in the absence of external challenges to DNA, pol zeta is essential for preventing replication-dependent DNA breaks in every division of normal mammalian cells. Loss of pol zeta in slowly proliferating mouse cells in vivo may allow accumulation of chromosomal aberrations that could lead to tumorigenesis. Pol zeta is unique amongst TLS polymerases for its essential role in cell proliferation. PMID- 22319214 TI - A transposase strategy for creating libraries of circularly permuted proteins. AB - A simple approach for creating libraries of circularly permuted proteins is described that is called PERMutation Using Transposase Engineering (PERMUTE). In PERMUTE, the transposase MuA is used to randomly insert a minitransposon that can function as a protein expression vector into a plasmid that contains the open reading frame (ORF) being permuted. A library of vectors that express different permuted variants of the ORF-encoded protein is created by: (i) using bacteria to select for target vectors that acquire an integrated minitransposon; (ii) excising the ensemble of ORFs that contain an integrated minitransposon from the selected vectors; and (iii) circularizing the ensemble of ORFs containing integrated minitransposons using intramolecular ligation. Construction of a Thermotoga neapolitana adenylate kinase (AK) library using PERMUTE revealed that this approach produces vectors that express circularly permuted proteins with distinct sequence diversity from existing methods. In addition, selection of this library for variants that complement the growth of Escherichia coli with a temperature-sensitive AK identified functional proteins with novel architectures, suggesting that PERMUTE will be useful for the directed evolution of proteins with new functions. PMID- 22319215 TI - Prebiotically plausible mechanisms increase compositional diversity of nucleic acid sequences. AB - During the origin of life, the biological information of nucleic acid polymers must have increased to encode functional molecules (the RNA world). Ribozymes tend to be compositionally unbiased, as is the vast majority of possible sequence space. However, ribonucleotides vary greatly in synthetic yield, reactivity and degradation rate, and their non-enzymatic polymerization results in compositionally biased sequences. While natural selection could lead to complex sequences, molecules with some activity are required to begin this process. Was the emergence of compositionally diverse sequences a matter of chance, or could prebiotically plausible reactions counter chemical biases to increase the probability of finding a ribozyme? Our in silico simulations using a two-letter alphabet show that template-directed ligation and high concatenation rates counter compositional bias and shift the pool toward longer sequences, permitting greater exploration of sequence space and stable folding. We verified experimentally that unbiased DNA sequences are more efficient templates for ligation, thus increasing the compositional diversity of the pool. Our work suggests that prebiotically plausible chemical mechanisms of nucleic acid polymerization and ligation could predispose toward a diverse pool of longer, potentially structured molecules. Such mechanisms could have set the stage for the appearance of functional activity very early in the emergence of life. PMID- 22319216 TI - Dataset integration identifies transcriptional regulation of microRNA genes by PPARgamma in differentiating mouse 3T3-L1 adipocytes. AB - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a key transcription factor in mammalian adipogenesis. Genome-wide approaches have identified thousands of PPARgamma binding sites in mouse adipocytes and PPARgamma upregulates hundreds of protein-coding genes during adipogenesis. However, no microRNA (miRNA) genes have been identified as primary PPARgamma-targets. By integration of four separate datasets of genome-wide PPARgamma binding sites in 3T3-L1 adipocytes we identified 98 miRNA clusters with PPARgamma binding within 50 kb from miRNA transcription start sites. Nineteen mature miRNAs were upregulated >=2-fold during adipogenesis and for six of these miRNA loci the PPARgamma binding sites were confirmed by at least three datasets. The upregulation of five miRNA genes miR-103-1 (host gene Pank3), miR-148b (Copz1), miR-182/96/183, miR-205 and miR-378 (Ppargc1b) followed that of Pparg. The PPARgamma-dependence of four of these miRNA loci was demonstrated by PPARgamma knock-down and the loci of miR-103-1 (Pank3), miR-205 and miR-378 (Ppargc1b) were also responsive to the PPARgamma ligand rosiglitazone. Finally, chromatin immunoprecipitation analysis validated in silico predicted PPARgamma binding sites at all three loci and H3K27 acetylation was analyzed to confirm the activity of these enhancers. In conclusion, we identified 22 putative PPARgamma target miRNA genes, showed the PPARgamma dependence of four of these genes and demonstrated three as direct PPARgamma target genes in mouse adipogenesis. PMID- 22319217 TI - Arteriolar vascular smooth muscle cell differentiation in benign nephrosclerosis. AB - BACKGROUND: Benign nephrosclerosis (bN) is the most prevalent form of hypertensive damage in kidney biopsies. It is defined by early hyalinosis and later fibrosis of renal arterioles. Despite its high prevalence, very little is known about the contribution of arteriolar vascular smooth muscle cells (VSMCs) to bN. We examined classical and novel candidate markers of the normal contractile and the pro-fibrotic secretory phenotype of VSMCs in arterioles in bN. METHODS: Sixty-three renal tissue specimens with bN and eight control specimens were examined by immunohistochemistry for the contractile markers caldesmon, alpha-smooth muscle actin (alpha-SMA), JunB, smoothelin and the secretory marker S100A4 and by double stains for caldesmon or smoothelin with S100A4. RESULTS: Smoothelin immunostaining showed an inverse correlation with hyalinosis and fibrosis scores, while S100A4 correlated with fibrosis scores only. Neither caldesmon, alpha-SMA nor JunB correlated with hyalinosis or fibrosis scores. Cells in the arteriolar wall were exclusively positive either for caldesmon/smoothelin or S100A4. CONCLUSIONS: This is the first systematic analysis of VSMC differentiation in bN. The results suggest that smoothelin is the most sensitive marker for the contractile phenotype and that S100A4 could be a novel marker for the secretory phenotype in vivo. The other markers did not seem to differentiate these phenotypes in bN. Thus, VSMC phenotype markers should be defined in the context of the vessel segment and disease under examination. S100A4 could not only be a marker of pro-fibrotic secretory VSMCs in bN but also an important mediator of arteriolar fibrosis. PMID- 22319218 TI - Hyporesponsiveness to erythropoiesis-stimulating agents and renal survival in non dialysis CKD patients. AB - BACKGROUND: Lower responsiveness to erythropoiesis-stimulating agents (ESA-R) predicts cardiovascular (CV) events. Whether ESA-R also affects the risk of end stage renal disease (ESRD) is unknown. METHODS: We evaluated ESA-R in 194 consecutive chronic kidney disease (CKD) patients, regularly seen in outpatient nephrology clinics, who started erythropoiesis-stimulating agent (ESA) therapy between 2002-06. Exclusion criteria were causes of anaemia other than CKD or recent transfusion. ESA-R was calculated as (Hb1-Hb0)/time/ESA dose (g/dL/month/10 MUg/week of ESA). Patients were classified, from lower to higher tertile of ESA-R, as poor, intermediate and good responders. Time to ESRD was the primary outcome. RESULTS: Age was 64+/-16 years, 48% were male, 34% had diabetes and 32% had CV disease, glomerular filtration rate (GFR) 24+/-13 mL/min/1.73 m2 and proteinuria 0.6 g/dL (interquartile range 0.2-1.9). First ESA dose was 23.7+/ 10.8 MUg/week; haemoglobin (Hb) increased from 9.9+/-0.8 g/dL to 11.0+/-1.2 g/dL at first control, obtained after 1.4+/-0.4 months. These changes corresponded to an ESA-R of 0.37+/-0.38 g/dL/month/10 MUg/week of ESA and tertiles limits were 0.17 and 0.47. Poor responders were younger and had lower GFR and higher proteinuria than intermediate and good responders. During the first 6 months of ESA therapy, poor responders showed lower Hb levels and sustained longer periods of Hb level<11 g/dL. During follow-up (median 3.0 years), 99 patients reached ESRD. At multivariable Cox's analysis, poor responsiveness was associated with higher risk of ESRD (hazard ratio 2.49, 95% confidence interval 1.28-4.84). CONCLUSION: ESA-R predicts renal prognosis in CKD patients followed in nephrology practice, where ESRD is the predominant outcome and ESA is commonly used at low dose. PMID- 22319220 TI - Temporal changes in magnetic resonance imaging characteristics of Gliadel wafers and of the adjacent brain parenchyma. AB - Carmustine is used in the treatment of glioblastomas as locally applied chemotherapy in the form of biodegradable wafers, which are lined on the walls of the resection cavity at the end of the resection, to increase local concentrations and decrease systemic toxicity. A total of 44 patients with glioblastoma with gross macroscopic tumor removal were included. MRIs were performed at various times postoperatively (within 24 hours, 1 week, 1 month, 2 months, 3 months, 6 months, 9 months, and 1 year). MR protocols included a T2-, diffusion-weighted, and T1-weighted sequences with and without intravenous administration of gadolinium. On T1, the wafers change from their initial hypointense to an isointense appearance after a period during which they appear to be hypointense, with a hyperintense rim most prominent less than 1 month postoperatively. On T2 they change from a hypointense to an isointense appearance. Restricted diffusivity reshaping the silhouette of the wafer's surface at the rim of the resection cavity can be found as early as day 1 postoperatively; however, 1 month after implantation, they all show areas of restricted diffusion, which may remain up to 1 year. Contrast enhancement at the rim of the resection cavity can already be found at day 1 postoperatively, with a peak shortly after 1 month after surgery. These changes can easily be mistaken for an abscess and hamper the early differentiation between residual tumor tissue and normal postoperative changes. However, early changes in either appearance do not predict overall survival or the progression free interval. PMID- 22319221 TI - ? AB - A multidisciplinary study was performed on a c. 30 m thick, limnic-deltaic sequence in the Styrian Basin (Austria). Geophysical (gamma ray activity, rock magnetism), geochemical (organic carbon, sulphur) and sedimentological observations were combined with palaeontological information (mainly ostracods). On this base, several ecological factors were deduced (terrigenous influx, salinity, water depth and oxygenation). Based on integrated stratigraphy as well as on palaeomagnetic results the whole section is set to Chron C5r.2r-1n (11.308 11.263 Ma) and covers a period of less than 45 kyr. In addition to the long-term record, we analysed short-term changes by high-resolution sampling (5 mm sample interval; ostracods, magnetic susceptibility). This ~ 2.3 m-thick interval spans in total < 3500 yr with an individual sample resolution of a few years only. The combination of these data permit the description of the palaeoenvironmental evolution of the section in detail: at the base of the section, the development of a conifer swamp on the lakeside of Lake Pannon is documented. This almost freshwater swamp existed for some centuries before it became extinct within a few decades due to a rise of the water-table. The drowning is related to a transgression of Lake Pannon, which triggered the establishment of a brackish water fauna as well as greigite formation in the lake sediments. In general, the ongoing transgression favoured benthic life due to increased salinity (up to mesohaline conditions). The high-resolution ostracod and magnetic susceptibility record reflect short-term fluctuations in bottom-water ventilation. These oscillations probably range in the order of centuries and decades and are possibly related to climatic shifts. Later, the successive deepening of the lake resulted in a significant faunal turnover. A meromictic system with a well established, oxygen-depleted hypolimnion developed. Finally, the limnic phase was replaced by a prograding deltaic system, where the amplified input of coarse grained material and freshwater also affected benthic life. Periodic changes in clay (illite) content were detected by the gamma ray-log throughout the entire section. The observed cycles (5-12 kyr) of the gamma ray-log may reflect a super ordinate modulation of the sedimentary record by climatically forced changes in precipitation or run-off. PMID- 22319219 TI - Consensus on the role of human cytomegalovirus in glioblastoma. AB - The human cytomegalovirus (HCMV) and glioma symposium was convened on April 17, 2011 in Washington, DC, and was attended by oncologists and virologists involved in studying the relationship between HCMV and gliomas. The purpose of the meeting was to reach a consensus on the role of HCMV in the pathology of gliomas and to clarify directions for future research. First, the group summarized data that describe how HCMV biology overlaps with the key pathways of cancer. Then, on the basis of published data and ongoing research, a consensus was reached that there is sufficient evidence to conclude that HCMV sequences and viral gene expression exist in most, if not all, malignant gliomas, that HCMV could modulate the malignant phenotype in glioblastomas by interacting with key signaling pathways; and that HCMV could serve as a novel target for a variety of therapeutic strategies. In summary, existing evidence supports an oncomodulatory role for HCMV in malignant gliomas, but future studies need to focus on determining the role of HCMV as a glioma-initiating event. PMID- 22319222 TI - Real-time production of arguments and adjuncts in normal and agrammatic speakers. AB - Two eyetracking experiments examined the real-time production of verb arguments and adjuncts in healthy and agrammatic aphasic speakers. Verb argument structure has been suggested to play an important role during grammatical encoding (Bock & Levelt, 1994) and in speech deficits of agrammatic aphasic speakers (Thompson, 2003). However, little is known about how adjuncts are processed during sentence production. The present experiments measured eye movements while speakers were producing sentences with a goal argument (e.g., the mother is applying lotion to the baby) and a beneficiary adjunct phrase (e.g., the mother is choosing lotion for the baby) using a set of computer-displayed written words. Results showed that the sentence production system experiences greater processing cost for producing adjuncts than verb arguments and this distinction is preserved even after brain-damage. In Experiment 1, healthy young speakers showed greater gaze durations and gaze shifts for adjuncts as compared to arguments. The same patterns were found in agrammatic and older speakers in Experiment 2. Interestingly, the three groups of speakers showed different time courses for encoding adjuncts: young speakers showed greater processing cost for adjuncts during speech, consistent with incremental production (Kempen & Hoenkamp, 1987). Older speakers showed this difference both before speech onset and during speech, while aphasic speakers appeared to preplan adjuncts before speech onset. These findings suggest that the degree of incrementality may be affected by speakers' linguistic capacity. PMID- 22319223 TI - ? AB - Protective coatings for high temperature applications, as present e.g. during cutting and milling operations, require excellent mechanical and thermal properties during work load. The Ti(1 - x)Al(x)N system is industrially well acknowledged as it covers some of these requirements, and even exhibits increasing hardness with increasing temperature in its cubic modification, known as age hardening. The thermally activated diffusion at high temperatures however enables for the formation of wurtzite AlN, which causes a rapid reduction of mechanical properties in Ti(1 - x)Al(x)N coatings. The present work investigates the possibility to increase the formation temperature of w-AlN due to Hf alloying up to 10 at.% at the metal sublattice of Ti(1 - x)Al(x)N films. Ab initio predictions on the phase stability and decomposition products of quaternary Ti(1 x - y)Al(x)Hf(y)N alloys, as well as the ternary Ti(1 - x)Al(x)N, Hf(1 - x)Al(x)N and Ti(1 - z)Hf(z)N systems, facilitate the interpretation of the experimental findings. Vacuum annealing treatments from 600 to 1100 degrees C indicate that the isostructural decomposition, which is responsible for age hardening, of the Ti(1 - x - y)Al(x)Hf(y)N films starts at lower temperatures than the ternary Ti(1 - x)Al(x)N coating. However, the formation of a dual phase structure of c-Ti(1 - z)Hf(z)N (with z = y/(1 - x)) and w-AlN is shifted to ~ 200 degrees C higher temperatures, thus retaining a film hardness of ~ 40 GPa up to ~ 1100 degrees C, while the Hf free films reach the respective hardness maximum of ~ 38 GPa already at ~ 900 degrees C. Additional annealing experiments at 850 and 950 degrees C for 20 h indicate a substantial improvement of the oxidation resistance with increasing amount of Hf in Ti(1 - x - y)Al(x)Hf(y)N. PMID- 22319224 TI - ? AB - Transition metal aluminium nitride (TM-Al-N) thin films are valued for their excellent mechanical (e.g. hardness) as well as protective (e.g. oxidation resistance) properties. This paper addresses the structure and phase stability of group IVB TM-Al-N systems Ti(1-x)Al(x)N, Zr(1-x)Al(x)N, and Hf(1-x)Al(x)N. The predicted stability regions of the rock salt cubic structures are x <= 0.7, x <= 0.45, and x <= 0.45, respectively, while the wurtzite-type single phase field is obtained for x >= 0.7, x >= 0.68, and x >= 0.62 respectively. The predicted phase stability regions and the broad dual-phase transition regions in the case of Zr(1 x)Al(x)N and Hf(1-x)Al(x)N are validated by experiments. Furthermore, the phase transition from cubic to wurtzite with increasing Al content in the alloys is correlated with changes of electronic structure and bonding in the systems. PMID- 22319225 TI - Real-time production of unergative and unaccusative sentences in normal and agrammatic speakers: An eyetracking study. AB - BACKGROUND: Speakers with agrammatic aphasia have greater difficulty producing unaccusative (float) compared to unergative (bark) verbs (Kegl, 1995; Lee & Thompson, 2004; Thompson, 2003), putatively because the former involve movement of the theme to the subject position from the post-verbal position, and are therefore more complex than the latter (Burzio, 1986; Perlmutter, 1978). However, it is unclear if and how sentence production processes are affected by the linguistic distinction between these two types of verbs in normal and impaired speakers. AIMS: This study examined real-time production of sentences with unergative (the black dog is barking) vs unaccusative (the black tube is floating) verbs in healthy young speakers and individuals with agrammatic aphasia, using eyetracking. METHODS #ENTITYSTARTX00026; PROCEDURES: Participants' eye movements and speech were recorded while they produced a sentence using computer displayed written stimuli (e.g., black, dog, is barking). OUTCOMES #ENTITYSTARTX00026; RESULTS: Both groups of speakers produced numerically fewer unaccusative sentences than unergative sentences. However, the eye movement data revealed significant differences in fixations between the adjective (black) vs the noun (tube) when producing unaccusatives, but not when producing unergatives for both groups. Interestingly, whereas healthy speakers showed this difference during speech, speakers with agrammatism showed this difference prior to speech onset. CONCLUSIONS: These findings suggest that the human sentence production system differentially processes unaccusatives vs unergatives. This distinction is preserved in individuals with agrammatism; however, the time course of sentence planning appears to differ from healthy speakers (Lee & Thompson, 2010). PMID- 22319226 TI - A Hepatocellular Adenoma in a Diet-induced Obese Mouse. AB - A hepatic nodule was noted in a C57BL/6J mouse with diet-induced obesity at 53 weeks of age. Macroscopically, a protruding yellowish white nodule was observed on the visceral surface of the left lateral lobe. Light microscopy demonstrated clear demarcation from the compressed adjacent parenchyma, with loss of the distinct lobular pattern. The proliferating cells of the lesion varied in shape and showed cellular atypia and prominent nucleoli along with vacuoles of various sizes. Some of the cells contained various-sized eosinophilic inclusion bodies in their cytoplasm, and electron microscopy revealed the presence of lipid droplets in the rough endoplasmic reticulum. Eosinophilic inclusions were observed as electron dense granular material in the rough endoplasmic reticulum, with one or a few low density central cores. A diagnosis of hepatocellular adenoma was made based on these findings. PMID- 22319227 TI - The First Case of Feline Infectious Peritonitis-like Pyogranuloma in a Ferret Infected by Coronavirus in Japan. AB - A male ferret, which was purchased from abroad at 9 months of age, had shown significant weight loss starting at 13 months of age. The ferret subsequently showed decreasing motor activity and recumbency and was euthanized at 14 months of age. At necropsy, a white, quail egg-sized mass was found in the mesentery. Histopathologically, multifocal granulomas consisting of necrotic foci, macrophages, fibroblasts and plentiful fibrous connective tissues were observed in the mesenteric mass. Surrounding the granulomas, inflammatory cell infiltration consisting of neutrophils, lymphocytes and plasmacytes was observed diffusely and significantly. Immunohistochemistry revealed small numbers of macrophages around necrotic foci that were positively stained for anti-mouse feline coronavirus. Electron microscopically, the cytoplasm of the macrophages contained viral particles, which were identified as coronavirus. The histopathological features in this ferret were similar to those in cats with feline infectious peritonitis (FIP). This was the first case in ferrets in Japan. PMID- 22319228 TI - Spontaneous extraskeletal osteosarcoma in the stomach of an aged f344 rat. AB - Extraskeletal osteosarcoma is a very rare tumor in humans and animals including rats. This paper describes a case of extraskeletal osteosarcoma observed in the glandular stomach of an aged female Fischer 344 rat. Grossly, a whitish solid mass was observed at the greater curvature of the glandular stomach. Histologically, the tumor consisted of both atypical polygonal and pleomorphic spindle-shaped cells, with pleomorphic nuclei, and it contained variable amounts of osteoids and small clumps of mature bone tissue. In addition, mitotic figures were frequently observed. Neither invasion of the muscle layer or vessels in the stomach nor metastasis to distant organs was detected. There were no skeletal tumors in the body. Immunohistochemically, the tumor cells were positive for osteocalcin, osteonectin, vimentin and S-100 protein. Judging from these results, the present tumor was diagnosed as extraskeletal osteosarcoma. This is the first report of spontaneous extraskeletal osteosarcoma arising from the stomach in a rat. PMID- 22319229 TI - Bilateral cataract in a cynomolgus monkey. AB - Severe bilateral cataract was found in a 7 year-old naive female cynomolgus monkey (Macaca fascicularis) 3 months before necropsy. During macroscopic examination, severe opacity and thinning of the lens were observed in both eyes. Histopathology revealed that the lens nuclei and majority of cortex lens fibers had disappeared and become excavated, while the lens fibers in the subcapsular area were swollen and distorted. Other observations included atrophy and vacuolation in the lens epithelial cells and proliferation of spindle cells and collagen fiber beneath the anterior capsule of the right eye. Immunohistochemical staining of these spindle cells revealed the presence of vimentin, cytokeratin and alpha-smooth muscle actin (alpha-SMA), which were considered to be derived from lens epithelial cells. This is a rare case of spontaneous, bilateral, hypermature cataract in a cynomolgus monkey. PMID- 22319230 TI - High susceptibility to zymbal gland and intestinal carcinogenesis in diabetic Otsuka long-evans Tokushima Fatty rats. AB - Diabetes mellitus (DM) and obesity are believed to be risk factors for colorectal cancer in humans. In experiment 1, male nondiabetic Long-Evans Tokushima Otsuka (LETO) rats and Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model animal of type 2 DM, were whole-body X-irradiated (4 Gy) at 6 and 8 weeks of age and euthanized at 78 weeks of age (n=15, respectively). The incidences of small intestine adenocarcinoma in LETO and OLETF rats were 0% and 30%, respectively. In experiment 2, male LETO and OLETF rats (n=24, respectively) were given s.c. injections of 15 mg/kg azoxymethane (AOM) once weekly for 3 weeks and euthanized at 36 weeks of age. The incidences of Zymbal gland tumors in LETO and OLETF rats were 0% and 67%, respectively (P<0.001), whereas those of small intestine adenocarcinoma were 0% and 43% (P<0.001) and those of cecum/colon adenocarcinoma were 46% and 79% (P<0.05), respectively. Fatty change of hepatocytes was common in OLETF rats (63%) but not in LETO rats. Serum triglyceride and free fatty acid levels in OLETF rats were significantly higher than in LETO rats at sacrifice, whereas serum insulin levels in OLETF rats were very diverse. These data suggest that hyperlipidemia plays a significant role in high susceptibility to lower intestinal tract carcinogenesis in OLETF rats; this strain is susceptible to AOM induced Zymbal gland carcinogenesis. PMID- 22319231 TI - Background Data for General Toxicology Parameters in RccHan:WIST Rats at 8, 10, 19 and 32 Weeks of Age. AB - Recently, RccHan(TM):WIST (Wistar Hannover) rats were introduced to toxicity studies in Japan. The present study was performed to obtain control data for general toxicological parameters as an aid for interpretation of results in toxicity studies using this strain of rats. Four test groups comprising of 25 male and 25 female RccHan(TM):WIST rats were housed for 2, 4, 13 or 26 weeks from 6 weeks of age and observed and examined for clinical observation, body weight, food consumption, urinalysis, hematology, blood chemistry, organ weight, necropsy and/or histopathology. Ophthalmological examination was not conducted in this study, and the data in this report were obtained from an ongoing 104-week background study in RccHan(TM):WIST rats. These data were compared with the historical control data of CD(SD) (Sprague-Dawley) and/or F344 (Fischer) rats. The body weights of RccHan(TM):WIST rats were lower than those of CD(SD) rats and higher than those of F344 rats. The ophthalmological examination revealed a greater incidence of focal corneal opacity. Histopathology revealed focal mineralization of the cornea and Berlin blue-positive pigmentation in the epididymal interstitium as well as hepatocytes. Other than the above, some minor differences were found in urinalysis, hematology, blood chemistry and organ weights as compared with CD(SD) rats. PMID- 22319232 TI - Concordance between Results of Medium-term Liver Carcinogenesis Bioassays and Long-term Findings for Carcinogenic 2-Nitropropane and Non-carcinogenic1 Nitropropane in F344 Rats. AB - This study was conducted to determine the concordance of results for a pair of structural isomers, 2-nitropropane (2-NP) and 1-nitropropane (1-NP), using the rat medium-term liver carcinogenesis bioassay (Ito test) and previously published long-term carcinogenicity tests. Male F344 rats were given a single intraperitoneal injection of DEN (200 mg/kg b.w.) to initiate hepatocarcinogenesis. After 2 weeks, they received per os 0, 0.8, 4 or 20 mg/kg/day of 2-NP or 1-NP six times a week and were subjected to two-thirds partial hepatectomy at week 3. Non-initiated groups receiving 0 or 20 mg/kg/day were also included. The animals were sacrificed for quantitative analysis of GST P-positive foci at week 8. With the highest dose of 2-NP, significantly increased numbers and areas of GST-P-positive foci were demonstrated as compared with the respective control but were not noted with 1-NP. In the non-DEN-initiated groups, many small GST-P-positive foci of less than 0.2 mm in diameter were also induced in the rats treated with 2-NP at 20 mg/kg/day but were lacking with 1-NP. These results strongly support that 2-NP is a complete hepatocarcinogen with a potent initiation activity, whereas 1-NP is not. PMID- 22319233 TI - Fetal and neonatal goiter in cynomolgus monkeys following administration of the antithyroid drug thiamazole at high doses to dams during pregnancy. AB - To evaluate morphologic alterations in the thyroid gland in the second generation in cynomolgus monkeys, pregnant dams were exposed to high doses of thiamazole. In Experiment A, dams received thiamazole intragastrically via a nasogastric catheter from gestation day (GD) 50 to GD 150 or on the day before delivery. Initially, the dose level was 20 mg/kg/day (10 mg/kg twice daily); however, the dose level was subsequently decreased to 5 mg/kg/day (2.5 mg/kg twice daily), since deteriorated general conditions were observed in two dams. Six out of seven neonates died on the day of birth. The cause of neonatal death was tracheal compression and suffocation from goiter. The transplacental exposure to thiamazole affected the fetal thyroid glands and induced goiter in all neonates. The surviving neonate was necropsied 767 days after discontinuation of thiamazole exposure and showed reversibility of the induced changes. In Experiment B, dams were intragastrically administered thiamazole at 5 mg/kg/day (2.5 mg/kg twice daily) for treatment periods from GDs 51 to 70, 71 to 90, 91 to 110, 111 to 130 and 131 to 150. All fetuses showed enlarged thyroid glands but were viable. Histopathologically, hypertrophy and/or hyperplastic appearance of the follicular epithelium of the thyroid gland was observed at the end of each treatment period. The most active appearance of the follicular epithelium, consisting of crowded pedunculated structure, was demonstrated at end of the treatment period from GD 131 to 150. This is the first report on the morphology of fetal and neonatal goiter in the cynomolgus monkey. PMID- 22319234 TI - Protective Effects of Platycodon grandiflorum Aqueous Extract on Thioacetamide induced Fulminant Hepatic Failure in Mice. AB - The aim of the present study was to evaluate the protective activity of aqueous extract from Platycodon grandiflorum (BC703) on thioacetamide (TA)-induced hepatotoxicity in mice. We found that BC703 significantly decreased mortality and the change in serum transaminase following TA administration. The group treated with BC703 at doses of 1, 5, and 10 mg/kg produced significant hepatoprotective effects against TA-induced liver damage by decreasing the activities of serum enzymes, nitric oxide and lipid peroxidation in dose-dependent manners. Histopathological studies further substantiated the protective effect of BC703. These results show the hepatoprotective activity of aqueous extract from Platycodon grandiflorum on thioacetamide-induced fulminant hepatic failure. PMID- 22319235 TI - Spontaneous vacuolar degeneration of the thyroid follicular epithelium in cynomolgus monkeys. AB - Vacuolar degeneration of the thyroid follicular epithelium was observed in two untreated female cynomolgus monkeys assigned to control groups. In light microscopy, large vacuoles containing a homogenous substance occupied the basal region of the epithelium, and the nuclei had shifted toward the apical region. The vacuoles showed negative reactions to PAS and thyroglobulin. Electron microscopic observation revealed dilatation of the rough endoplasmic reticulum corresponding to the vacuoles. The plasma TSH, T3 and T4 levels determined for the samples kept frozen were within the normal ranges, suggesting that the thyroid function was kept intact. PMID- 22319236 TI - A collision tumor consisting of granular cell tumor and adenocarcinoma in the uterus of an aged djungarian hamster. AB - A neoplastic nodular lesion consisting of an admixture of granular cell tumor and adenocarcinoma was found in the uterus of a 26-month-old Djungarian hamster. Neoplastic cells of the uterine adenocarcinoma showed an epithelial nature in their growth patterns and by cytokeratin-immunopositive reaction, exhibiting nuclear pleomorphism. The granular cells had an abundant amount of fine granular eosinophilic cytoplasm and eccentric or central nuclei with no nuclear atypia; the granular structures were positive for periodic acid-Schiff with diastase resistance and were confirmed as lysosomes/autophagosomes by electron microscopy; immunohistochemically, the cells reacted to desmin, vimentin and alpha-smooth muscle actin and negatively for neurogenic, histiocyte/macrophage or epithelial markers, indicating smooth muscle origin. Because these tumors were generated from different cell origins, a diagnosis of collision tumor was made. PMID- 22319237 TI - Spontaneous Subcutaneous Sarcoma in a 50-week-old Male Wistar Hannover GALAS Rat. AB - A subcutaneous mass was noted in the abdomen of a 50-week-old male Wistar Hannover GALAS rat. Histologically, the tumor was composed of vimentin-positive small round cells with scant cytoplasm arranged in a trabecular, sheet or pericytoma-like pattern and spindle cells arranged in a bundle pattern and vimentin-negative round cells proliferating in an island-shaped pattern. Argentophilic thin fibers were observed to wrap up the individual cells, and some of the tumor cells showed coexpression of vimentin and cytokeratin that formed juxtanuclear globes in the cytoplasm by double immunohistostaining. Transmission electron microscopy did not reveal any characteristic features suggesting cellular differention toward a specific cell type. Based on these findings, it was difficult to specify the origin, and the tumor was diagnosed as a poorly differentiated mesenchymal tumor and classified as a sarcoma, NOS (not otherwise specified). PMID- 22319238 TI - Immunohistochemical and ultrastructural analyses of cytoplasmic blood plasma inclusions of rat hepatocytes. AB - In the present study, we investigated the histological, immunohistochemical and ultrastructural characteristics of cytoplasmic blood plasma inclusions that spontaneously occurred in a rat liver. Histologically, a number of cytoplasmic inclusions were observed in the liver of an 8-week-old female SD rat. These inclusions were strongly positive for PAS staining and resistant to diastase digestion. Immunohistochemical analyses revealed that these inclusions were positive for albumin and IgG; however, most of them were negative for LAMP-1 and LAMP-2. Ultrastructurally, the inclusions were surrounded by limiting membranes and composed of moderately electron dense, homogenous materials. These characteristics described here represent valuable information for pathological examination in toxicity studies. PMID- 22319239 TI - A Case Report of a Malignant Fibrous Histiocytoma in a T-cell Receptor beta Chain and p53 Double-knockout Mouse. AB - A subcutaneous tumor was found in the right abdomen of a 16-week-old male TCRbeta and p53 double-knockout mouse. The tumor had indistinct borders with the surrounding tissue. The cut surface after formalin fixation was pale yellowish white, partially dark red and partly white. Histologically, the tumor was composed of three distinct regions. The first region showed pleomorphic cells arranged in sheets. The second region showed spindle cells arranged in interlacing fascicles. The final region contained a mixture of the above mentioned two types of cells. Furthermore, a small amount of collagen fibers, round cells, multinucleated giant cells, and cells with eosinophilic granules were observed between these tumor cells. Immunohistochemical examination and electron microscopy identified that the pleomorphic cells and spindle cells were histiocytes and fibroblasts, respectively, and that the round cells were undifferentiated mesenchymal cells. Based on these findings, the tumor was diagnosed as a malignant fibrous histiocytoma. PMID- 22319240 TI - Immunohistochemical Expressions of Main PGE(2) Biosynthesis-related Enzymes and PGE(2) Receptor in Rat Nephrogenesis. AB - Endogenous prostaglandin (PG) E(2) plays important roles in renal homeostasis. Immunoexpressions of PGE(2) biosynthesis-related enzymes, cyclooxygenase (COX)-2 and microsomal PGE(2) synthetase (mPGES)-1 and EP4 (a PGE(2) receptor), were investigated in renal development. Kidney tissues were obtained from fetuses on gestation days 18 and 21 and neonates on days 1 to 18. In fetuses and early neonates, the expressions of COX-2, mPGES-1 and EP4 were observed in developing renal tubules, indicating that COX-2 and its product, PGE(2), play important roles in blastemal cell-derived renal tubular development via EP4. Cyclin D1 expression was seen in both the nucleus and cytoplasm of the developing tubules. These findings differed from the decreased COX-2 expression and exclusive nuclear expression of cyclin D1 seen in abnormal epithelial regeneration of injured renal tubules in cisplatin-treated rats in our previous articles. Collectively, PGE(2), induced by COX-2, regulates renal tubular epithelial formation via EP4. PMID- 22319241 TI - Synergistic applications of MD and NMR for the study of biological systems. AB - Modern biological sciences are becoming more and more multidisciplinary. At the same time, theoretical and computational approaches gain in reliability and their field of application widens. In this short paper, we discuss recent advances in the areas of solution nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations that were made possible by the combination of both methods, that is, through their synergistic use. We present the main NMR observables and parameters that can be computed from simulations, and how they are used in a variety of complementary applications, including dynamics studies, model-free analysis, force field validation, and structural studies. PMID- 22319242 TI - Thin-layer hydroxyapatite deposition on a nanofiber surface stimulates mesenchymal stem cell proliferation and their differentiation into osteoblasts. AB - Pulsed laser deposition was proved as a suitable method for hydroxyapatite (HA) coating of coaxial poly-E-caprolactone/polyvinylalcohol (PCL/PVA) nanofibers. The fibrous morphology of PCL/PVA nanofibers was preserved, if the nanofiber scaffold was coated with thin layers of HA (200 nm and 400 nm). Increasing thickness of HA, however, resulted in a gradual loss of fibrous character. In addition, biomechanical properties were improved after HA deposition on PCL/PVA nanofibers as the value of Young's moduli of elasticity significantly increased. Clearly, thin-layer hydroxyapatite deposition on a nanofiber surface stimulated mesenchymal stem cell viability and their differentiation into osteoblasts. The optimal depth of HA was 800 nm. PMID- 22319243 TI - Adult bone marrow: which stem cells for cellular therapy protocols in neurodegenerative disorders? AB - The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs). In this paper, we will review all information available concerning NCSC from adult tissues and their possible use in regenerative medicine. Moreover, as multiple recent studies showed the beneficial effect of bone marrow stromal cells in neurodegenerative diseases, we will discuss which stem cells isolated from adult bone marrow should be more suitable for cell replacement therapy. PMID- 22319244 TI - BMP9-induced osteogenetic differentiation and bone formation of muscle-derived stem cells. AB - Efficient osteogenetic differentiation and bone formation from muscle-derived stem cells (MDSCs) should have potential clinical applications in treating nonunion fracture healing or bone defects. Here, we investigate osteogenetic differentiation ability of MDSCs induced by bone morphogenetic protein 9 (BMP9) in vitro and bone formation ability in rabbit radius defects repairing model. Rabbit's MDSCs were extracted by type I collagenase and trypsin methods, and BMP9 was introduced into MDSCs by infection with recombinant adenovirus. Effects of BMP9-induced osteogenetic differentiation of MDSCs were identified with alkaline phosphatase (ALP) activity and expression of later marker. In stem-cell implantation assay, MDSCs have also shown valuable potential bone formation ability induced by BMP9 in rabbit radius defects repairing test. Taken together, our findings suggest that MDSCs are potentiated osteogenetic stem cells which can be induced by BMP9 to treat large segmental bone defects, nonunion fracture, and/or osteoporotic fracture. PMID- 22319245 TI - An elevated D-dimer value: a burden on our patients and hospitals. AB - With 200,000 annual deaths in the United States due to pulmonary embolism (PE), efficient and accurate diagnosis is mandatory. Since negative D-dimer values are only useful in ruling out PE, elevated values alone should not result in excessive testing. This study assessed the diagnostic and financial yield of the D-dimer in diagnosing PE. This retrospective review of 220 medical records of patients at a South Chicago Community Hospital explored the extent of the work-up following an elevated D-dimer for a suspected PE. Patients were randomly selected with no exclusion criteria. Five of the 118 (4.2%) patients with elevated D-dimer values were diagnosed with a PE. Tests ordered based on elevated D-dimer values were billed for more than $200,000. The current diagnostic approach has been medically and financially inefficient. Patients should not be worked-up for a PE based primarily on an elevated D-dimer value. Two prominent factors, independent of PE, that result in elevated D-dimer values and were pertinent to the studied population, are age and African-American origin. Implementing a scoring system, like the revised-Geneva scale, will establish a better index of suspicion to improve both the physician's diagnostic approach and the yield of the work-up. PMID- 22319246 TI - Surgical treatment of postintubation tracheal stenosis: Iranian experience of effect of previous tracheostomy. AB - BACKGROUND: Postintubation tracheal stenosis remains the most common indication for tracheal surgery. In the event of a rapid and progressive course of the disease after extubation, surgical approaches such as primary resection and anastomosis or various methods of tracheoplasty should be selected. We report our experience with surgical management of moderate to severe postintubation tracheal stenosis. We also compared intraoperative variables in postintubation tracheal stenosis between those with and without previous tracheostomy. METHODS: Over a 5 year period from June 2005 to July 2010, 50 patients aged 14-64 years with moderate (50%-70% of the lumen) to severe (>70%) postintubation tracheal stenosis underwent resection and primary anastomosis. Patients were followed up to assess the surgical outcome. To study the effect of previous tracheostomy on treatment, surgical variables were compared between patients with previous tracheostomy (group A, n = 27) and those without previous tracheostomy (group B, n = 23). RESULTS: Resection and primary anastomosis was performed via either cervical incision (45 patients) or right thoracotomy (five patients). In two patients with subglottic stenosis, complete resection of the tracheal lesion and anterior portion of cricoid cartilage was performed, and the remaining trachea was anastomosed to the thyroid cartilage using a Montgomery T-tube. There was only one perioperative death in a patient with a tracheo-innominate fistula. The length of the resected segment, number of resected rings, and subsequent duration of surgery were significantly greater in group A compared with group B (P < 0.05). Six months after surgery, the outcome was satisfactory to excellent in 47 (95.9%) patients. CONCLUSION: This surgical approach leads to highly successful results in the treatment of moderate to severe postintubation tracheal stenosis. In addition, previous tracheostomy might prolong the duration of surgery and increase the need for postoperative interventions due to an increase in the length and number of resected tracheal segments. Therefore, in the event of emergency tracheostomy in postintubation tracheal stenosis, insertion of the tracheostomy tube close to the stenotic segment is recommended. PMID- 22319247 TI - Sensitivity and specificity of median nerve ultrasonography in diagnosis of carpal tunnel syndrome. AB - BACKGROUND: Although controversial, recent studies have demonstrated advantages of sonographic techniques in the diagnosis of carpal tunnel syndrome (CTS). The purpose of this study was to assess the utility of median nerve ultrasonography in the diagnosis of CTS in Iranian patients. METHODS: Ninety patents with clinically suspected CTS were studied. Based on gold standard electromyography/nerve conduction velocity studies, wrists with CTS were divided into three groups on the basis of severity of CTS, ie, mild, moderate, and severe. In addition, both sides of the wrist were examined using sonography. Transverse images of the median nerve were obtained and median nerve cross section areas were measured at three levels, ie, immediately proximal to the carpal tunnel inlet, at the carpal tunnel inlet, and at the carpal tunnel outlet. Furthermore, flexor retinaculum thickness was evaluated. RESULTS: The mean age of the studied patients was 48.52 +/- 12.17 years. Median values of the median nerve cross-section at the carpal tunnel inlet, carpal tunnel outlet, and proximal carpal tunnel significantly differed between the wrists with and without CTS (P < 0.05). Comparisons between the CTS groups (mild, moderate, and severe) and non CTS wrists demonstrated that the median cross-sections of median nerve at the carpal tunnel inlet, carpal tunnel outlet, and inlet proximal carpal tunnel were significantly greater in the severe CTS group than in the other three groups (P < 0.05). The results showed that the median nerve cross-section at the three levels of carpal tunnel could only fairly differentiate severe CTS from other cases. CONCLUSION: The present study demonstrated that median nerve ultrasonography cannot replace the gold standard test (nerve conduction velocity) for the diagnosis of CTS because of low overall sensitivity and specificity, although it might provide useful information in some patients. PMID- 22319248 TI - Acute radiation syndrome (ARS) - treatment of the reduced host defense. AB - BACKGROUND: The current radiation threat from the Fukushima power plant accident has prompted rethinking of the contingency plan for prophylaxis and treatment of the acute radiation syndrome (ARS). The well-documented effect of the growth factors (granulocyte colony-stimulating factor [G-CSF] and granulocyte-macrophage colony-stimulating factor [GM-CSF]) in acute radiation injury has become standard treatment for ARS in the United States, based on the fact that growth factors increase number and functions of both macrophages and granulocytes. METHODS: Review of the current literature. RESULTS: The lungs have their own host defense system, based on alveolar macrophages. After radiation exposure to the lungs, resting macrophages can no longer be transformed, not even during systemic administration of growth factors because G-CSF/GM-CSF does not penetrate the alveoli. Under normal circumstances, locally-produced GM-CSF receptors transform resting macrophages into fully immunocompetent dendritic cells in the sealed-off pulmonary compartment. However, GM-CSF is not expressed in radiation injured tissue due to defervescence of the macrophages. In order to maintain the macrophage's important role in host defense after radiation exposure, it is hypothesized that it is necessary to administer the drug exogenously in order to uphold the barrier against exogenous and endogenous infections and possibly prevent the potentially lethal systemic infection, which is the main cause of death in ARS. RECOMMENDATION: Preemptive treatment should be initiated after suspected exposure of a radiation dose of at least <2 Gy by prompt dosing of 250 400 MUg GM-CSF/m(2) or 5 MUg/kg G-CSF administered systemically and concomitant inhalation of GM-CSF < 300 mcg per day for at least 14-21 days. CONCLUSION: The present United States standard for prevention and treatment of ARS standard intervention should consequently be modified into the combined systemic administration of growth factors and inhaled GM-CSF to ensure the sustained systemic and pulmonary host defense and thus prevent pulmonary dysfunction. PMID- 22319249 TI - Initial assessment and treatment with the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach. AB - The Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach is applicable in all clinical emergencies for immediate assessment and treatment. The approach is widely accepted by experts in emergency medicine and likely improves outcomes by helping health care professionals focusing on the most life threatening clinical problems. In an acute setting, high-quality ABCDE skills among all treating team members can save valuable time and improve team performance. Dissemination of knowledge and skills related to the ABCDE approach are therefore needed. This paper offers a practical "how-to" description of the ABCDE approach. PMID- 22319250 TI - Epigenetic regulation of fetal bone development and placental transfer of nutrients: progress for osteoporosis. AB - Osteoporosis is a common age-related disorder and causes acute and long-term disability and economic cost. Many factors influence the accumulation of bone minerals, including heredity, diet, physical activity, gender, endocrine functions, and risk factors such as alcohol, drug abuse, some pharmacological drugs or cigarette smoking. The pathology of bone development during intrauterine life is a factor for osteoporosis. Moreover, the placental transfer of nutrients plays an important role in the building of bones of fetuses. The importance of maternal calcium intake and vitamin D status are highlighted in this review. Various environmental factors including nutrition state or maternal stress may affect the epigenetic state of a number of genes during fetal development of bones. Histone modifications as histone hypomethylation, histone hypermethylation, hypoacetylation, etc. are involved in chromatin remodeling, known to contribute to the epigenetic landscape of chromosomes, and play roles in both fetal bone development and osteoporosis. This review will give an overview of epigenetic modulation of bone development and placental transfer of nutrients. In addition, the data from animal and human studies support the role of epigenetic modulation of calcium and vitamin D in the pathogenesis of osteoporosis. We review the evidence suggesting that various genes are involved in regulation of osteoclast formation and differentiation by osteoblasts and stem cells. Epigenetic changes in growth factors as well as cytokines play a rol in fetal bone development. On balance, the data suggest that there is a link between epigenetic changes in placental transfer of nutrients, including calcium and vitamin D, abnormal intrauterine bone development and pathogenesis of osteoporosis. PMID- 22319251 TI - Toxicological aspects of the use of phenolic compounds in disease prevention. AB - The consumption of a diet low in fat and enhanced by fruits and vegetables, especially rich in phenolic compounds, may reduce risks of many civilization diseases. The use of traditional medicines, mainly derived from plant sources, has become an attractive segment in the management of many lifestyle diseases. Concerning the application of dietary supplements (based on phenolic compounds) in common practice, the ongoing debate over possible adverse effects of certain nutrients and dosage levels is of great importance. Since dietary supplements are not classified as drugs, their potential toxicities and interactions have not been thoroughly evaluated. First, this review will introduce phenolic compounds as natural substances beneficial for human health. Second, the potential dual mode of action of flavonoids will be outlined. Third, potential deleterious impacts of phenolic compounds utilization will be discussed: pro-oxidant and estrogenic activities, cancerogenic potential, cytotoxic effects, apoptosis induction and flavonoid-drug interaction. Finally, future trends within the research field will be indicated. PMID- 22319252 TI - Trichosanthes dioica root extract induces tumor proliferation and attenuation of antioxidant system in albino mice bearing Ehrlich ascites carcinoma. AB - Trichosanthes dioica Roxb. (Cucurbitaceae), called pointed gourd in English, is a dioecious climber grown widely in the Indian subcontinent. The present study assessed the influence of treatment of hydroalcoholic extract of Trichosanthes dioica root (TDA) on Ehrlich ascites carcinoma (EAC) in Swiss albino mice with effects on antioxidant systems. Twenty-four hours after intraperitoneal inoculation of tumor (EAC) cells in mice, TDA was administered at 25 and 50 mg/kg for 8 consecutive days. On the 9(th) day, half of the mice were sacrificed for estimation of tumor proliferation, hematological, and hepatic antioxidative parameters. The rest were kept for assessment of survival parameters. TDA exhibited dose dependent and significant increase in tumor weight, tumor volume, packed cell volume and viable cells and reduced non-viable cells and life span of EAC bearing animals. Hematological parameters were significantly worsened in TDA treated mice. TDA treatment significantly aggravated the hepatic antioxidative parameters. The present study demonstrated that T. dioica root possessed tumor promoting activity in EAC bearing albino mice, plausibly mediated by attenuation of endogenous antioxidant systems. PMID- 22319253 TI - Effects of reactive oxygen species and neutrophils on endothelium-dependent relaxation of rat thoracic aorta. AB - Reactive oxygen species (ROS) are produced in different metabolic processes including the respiratory burst of neutrophils accompanying local inflammation. The aim of this study was to analyze the effects of N-formyl-methionyl-leucyl phenylalanine (FMLP)-activated neutrophils, isolated from the guinea pig peritoneal cavity, on isolated rings of a large (conduit) artery, the rat thoracic aorta. FMLP-activated neutrophils enhanced the basal tension increased by alpha(1)-adrenergic stimulation. In phenylephrine-precontracted aortae, they elicited marked contraction, while in noradrenaline-precontracted rat aortal rings they caused a biphasic response (contraction-relaxation). To eliminate interaction of activated neutrophils with catecholamines, in the subsequent experiments the basal tension was increased by KCl-induced depolarization. Activated neutrophils evoked a low-amplitude biphasic response (relaxation contraction) on the KCl-induced contraction. Not only the acetylcholine- and A(23187)-induced relaxations but also the catalase sensitive hydrogen peroxide (H(2)O(2)) elicited contractions were endothelium-dependent. Even though the acetylcholine-induced relaxation was changed by activated neutrophils and by the ROS studied, their effects differed significantly, yet none of them did eliminate fully the endothelium-dependent acetylcholine relaxation. The effect of activated neutrophils resembled the effect of superoxide anion radical (O(2) (*-)) produced by xanthine/xanthine oxidase (X/XO) and differed from the inhibitory effects of Fe(2)SO(4)/H(2)O(2)-produced hydroxyl radical ((*)OH) and H(2)O(2). Thus O(2) (* ) produced either by activated neutrophils or X/XO affected much less the endothelium-dependent acetylcholine-activated relaxation mechanisms than did (*)OH and H(2)O(2). In the large (conduit) artery, the effects of activated neutrophils and various ROS (O(2) (*-), (*)OH and H(2)O(2)) seem to be more dependent on muscle tension than on endothelial mechanisms. PMID- 22319254 TI - Unrecorded alcohol consumption in Russia: toxic denaturants and disinfectants pose additional risks. AB - In 2005, 30% of all alcohol consumption in Russia was unrecorded. This paper describes the chemical composition of unrecorded and low cost alcohol, including a toxicological evaluation. Alcohol products (n=22) from both recorded and unrecorded sources were obtained from three Russian cities (Saratov, Lipetsk and Irkutsk) and were chemically analyzed. Unrecorded alcohols included homemade samogons, medicinal alcohols and surrogate alcohols. Analysis included alcoholic strength, levels of volatile compounds (methanol, acetaldehyde, higher alcohols), ethyl carbamate, diethyl phthalate (DEP) and polyhexamethyleneguanidine hydrochloride (PHMG). Single samples showed contamination with DEP (275-1269 mg/l) and PHMG (515 mg/l) above levels of toxicological concern. Our detailed chemical analysis of Russian alcohols showed that the composition of vodka, samogon and medicinal alcohols generally did not raise major public health concerns other than for ethanol. It was shown, however, that concentration levels of DEP and PHMG in some surrogate alcohols make these samples unfit for human consumption as even moderate drinking would exceed acceptable daily intakes. PMID- 22319255 TI - Acute toxicity studies of aqueous leaf extract of Phyllanthus niruri. AB - Phyllanthus niruri is a plant with medicinal properties. It is often used to treat mild malaria and the elimination of renal stones. However, studies on its toxicity are scarce. The study was carried out to determine if the aqueous leaf extract of P. niruri administered to female Sprague-Dawley rats would illicit evidence of toxicity. Fifteen female rats weighing 150-200 g were divided into 3 groups. Rats in Group 1 were given a single low dose (LD) of 2000 mg/kg b.w. of the extract by oral gavage within 24 hrs. Rats in Group 2 were given a single high dose (HD) of 5000 mg/kg b.w. of the extract by oral gavage within 24 hrs. Rats in Group 3 were not given any extract but drinking water and served as the control group (C). All the rats were observed for signs of toxidromes for 14 days. On the 15(th) day, all the rats were sacrificed. Body organs were harvested for macroscopic examination. Urine and blood samples were drawn and analyzed. Hematological tests performed included full blood count and hemoglobin. Biochemical examinations included bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin, globulin, alkaline phosphatse (ALP), gamma-glutamyltranspeptidase (GGT), urea, and creatinine. The results of the three groups were not significantly different. Examination of the various body organs did not show any abnormality. Thus no toxicity was observed at the levels administered. The LD(50) of the aqueous extract is>5000 mg/kg. b.w. PMID- 22319256 TI - Anxiolytic activity of pyridoindole derivatives SMe1EC2 and SMe1M2: behavioral analysis using rat model. AB - Anxiety and mood disorders have become very significant affections in the last decades. According to WHO at least one mental disease occurred per year in 27% of EU inhabitants (more than 82 mil. people). It is estimated that by 2020, depression will be the main cause of morbidity in the developed countries. These circumstances call for research for new prospective drugs with anxiolytic and antidepressive properties exhibiting no toxicity and withdrawal effect and possessing beneficial properties, like antioxidant and/or neuroprotective effects. The aim of this study was to obtain information about psychopharmacological properties of pyridoindole derivatives SMe1EC2 and SMe1M2, using non-invasive behavioral methods in rats.The battery of ethological tests (open field, elevated plus-maze, light/dark box exploration, forced swim test) was used to obtain information about anxiolytic and antidepressant activity of the pyridoindole derivatives. The substances were administered intraperitoneally 30 minutes before the tests at doses of 1, 10 and 25 mg/kg.In the behavioral tests, SMe1EC2 was found to exert anxiolytic activity in elevated plus maze with no affection of locomotor activity. The highest dose of SMe1M2 increased the time spent in the lit part of the Light/Dark box, however this result was influenced by inhibition of motor activity of the rats. Similar findings were observed also in elevated plus-maze, although these results were not statistically significant.In conclusion, from the results of our study it is evident that both pyridoindoles acted on the CNS. In the highest dose, SMe1M2 was found to possess rather sedative than anxiolytic or antidepressant activity. PMID- 22319257 TI - Estimation of biological oxygen demand and chemical oxygen demand for combined sewer systems using synchronous fluorescence spectra. AB - Real-time monitoring of water quality for sewer system is required for efficient sewer network design because it provides information on the precise loading of pollutant to wastewater treatment facilities and the impact of loading on receiving water. In this study, synchronous fluorescence spectra and its first derivatives were investigated using a number of wastewater samples collected in sewer systems in urban and non-urban areas, and the optimum fluorescence feature was explored for the estimation of biochemical oxygen demand (BOD) and chemical oxygen demand (COD) concentrations of sewer samples. The temporal variations in BOD and COD showed a regular pattern for urban areas whereas they were relatively irregular for non-urban areas. Irrespective of the sewer pipes and the types of the areas, two distinct peaks were identified from the synchronous fluorescence spectra, which correspond to protein-like fluorescence (PLF) and humic-like fluorescence (HLF), respectively. HLF in sewer samples appears to be associated with fluorescent whitening agents. Five fluorescence characteristics were selected from the synchronous spectra and the first-derivatives. Among the selected fluorescence indices, a peak in the PLF region (i.e., Index I) showed the highest correlation coefficient with both BOD and COD. A multiple regression approach based on suspended solid (SS) and Index I used to compensate for the contribution of SS to BOD and COD revealed an improvement in the estimation capability, showing good correlation coefficients of 0.92 and 0.94 for BOD and COD, respectively. PMID- 22319258 TI - Development of a low-cost attitude and heading reference system using a three axis rotating platform. AB - A development procedure for a low-cost attitude and heading reference system (AHRS) with a self-developed three-axis rotating platform has been proposed. The AHRS consists of one 3-axis accelerometer, three single-axis gyroscopes, and one 3-axis digital compass. Both the accelerometer and gyroscope triads are based on micro electro-mechanical system (MEMS) technology, and the digital compass is based on anisotropic-magnetoresistive (AMR) technology. The calibrations for each sensor triad are readily accomplished by using the scalar calibration and the least squares methods. The platform is suitable for the calibration and validation of the low-cost AHRS and it is affordable for most laboratories. With the calibrated parameters and data fusion algorithm for the orientation estimation, the self-developed AHRS demonstrates the capabilities of compensating for the sensor errors and outputting the estimated orientation in real-time. The validation results show that the estimated orientations of the developed AHRS are within the acceptable region. This verifies the practicability of the proposed development procedure. PMID- 22319259 TI - DFB lasers between 760 nm and 16 MUm for sensing applications. AB - Recent years have shown the importance of tunable semiconductor lasers in optical sensing. We describe the status quo concerning DFB laser diodes between 760 nm and 3,000 nm as well as new developments aiming for up to 80 nm tuning range in this spectral region. Furthermore we report on QCL between 3 MUm and 16 MUm and present new developments. An overview of the most interesting applications using such devices is given at the end of this paper. PMID- 22319261 TI - The comparison of environmental effects on michelson and fabry-perot interferometers utilized for the displacement measurement. AB - The optical structure of general commercial interferometers, e.g., the Michelson interferometers, is based on a non-common optical path. Such interferometers suffer from environmental effects because of the different phase changes induced in different optical paths and consequently the measurement precision will be significantly influenced by tiny variations of the environmental conditions. Fabry-Perot interferometers, which feature common optical paths, are insensitive to environmental disturbances. That would be advantageous for precision displacement measurements under ordinary environmental conditions. To verify and analyze this influence, displacement measurements with the two types of interferometers, i.e., a self-fabricated Fabry-Perot interferometer and a commercial Michelson interferometer, have been performed and compared under various environmental disturbance scenarios. Under several test conditions, the self-fabricated Fabry-Perot interferometer was obviously less sensitive to environmental disturbances than a commercial Michelson interferometer. Experimental results have shown that induced errors from environmental disturbances in a Fabry-Perot interferometer are one fifth of those in a Michelson interferometer. This has proved that an interferometer with the common optical path structure will be much more independent of environmental disturbances than those with a non-common optical path structure. It would be beneficial for the solution of interferometers utilized for precision displacement measurements in ordinary measurement environments. PMID- 22319262 TI - A multi-point sensor based on optical fiber for the measurement of electrolyte density in lead-acid batteries. AB - This article describes a multi-point optical fiber-based sensor for the measurement of electrolyte density in lead-acid batteries. It is known that the battery charging process creates stratification, due to the different densities of sulphuric acid and water. In order to study this process, density measurements should be obtained at different depths. The sensor we describe in this paper, unlike traditional sensors, consists of several measurement points, allowing density measurements at different depths inside the battery. The obtained set of measurements helps in determining the charge (SoC) and state of health (SoH) of the battery. PMID- 22319260 TI - State-of-the-art of (bio)chemical sensor developments in analytical Spanish groups. AB - (Bio)chemical sensors are one of the most exciting fields in analytical chemistry today. The development of these analytical devices simplifies and miniaturizes the whole analytical process. Although the initial expectation of the massive incorporation of sensors in routine analytical work has been truncated to some extent, in many other cases analytical methods based on sensor technology have solved important analytical problems. Many research groups are working in this field world-wide, reporting interesting results so far. Modestly, Spanish researchers have contributed to these recent developments. In this review, we summarize the more representative achievements carried out for these groups. They cover a wide variety of sensors, including optical, electrochemical, piezoelectric or electro-mechanical devices, used for laboratory or field analyses. The capabilities to be used in different applied areas are also critically discussed. PMID- 22319263 TI - Vertical guidance performance analysis of the L1-L5 dual-frequency GPS/WAAS user avionics sensor. AB - This paper investigates the potential vertical guidance performance of global positioning system (GPS)/wide area augmentation system (WAAS) user avionics sensor when the modernized GPS and Galileo are available. This paper will first investigate the airborne receiver code noise and multipath (CNMP) confidence (sigmaair). The sigmaair will be the dominant factor in the availability analysis of an L1-L5 dual-frequency GPS/WAAS user avionics sensor. This paper uses the MATLAB Algorithm Availability Simulation Tool (MAAST) to determine the required values for the sigmaair, so that an L1-L5 dual-frequency GPS/WAAS user avionics sensor can meet the vertical guidance requirements of APproach with Vertical guidance (APV) II and CATegory (CAT) I over conterminous United States (CONUS). A modified MAAST that includes the Galileo satellite constellation is used to determine under what user configurations WAAS could be an APV II system or a CAT I system over CONUS. Furthermore, this paper examines the combinations of possible improvements in signal models and the addition of Galileo to determine if GPS/WAAS user avionics sensor could achieve 10 m Vertical Alert Limit (VAL) within the service volume. Finally, this paper presents the future vertical guidance performance of GPS user avionics sensor for the United States' WAAS, Japanese MTSAT-based satellite augmentation system (MSAS) and European geostationary navigation overlay service (EGNOS). PMID- 22319264 TI - Following enzyme activity with infrared spectroscopy. AB - Fourier transform infrared (FTIR) spectroscopy provides a direct, "on-line" monitor of enzymatic reactions. Measurement of enzymatic activity is based on the fact that the infrared spectra of reactants and products of an enzymatic reaction are usually different. Several examples are given using the enzymes pyruvate kinase, fumarase and alcohol dehydrogenase. The main advantage of the infrared method is that it observes the reaction of interest directly, i.e., no activity assay is required to convert the progress of the reaction into an observable quantity. PMID- 22319265 TI - Sensing and tactile artificial muscles from reactive materials. AB - Films of conducting polymers can be oxidized and reduced in a reversible way. Any intermediate oxidation state determines an electrochemical equilibrium. Chemical or physical variables acting on the film may modify the equilibrium potential, so that the film acts as a sensor of the variable. The working potential of polypyrrole/DBSA (Dodecylbenzenesulfonic acid) films, oxidized or reduced under constant currents, changes as a function of the working conditions: electrolyte concentration, temperature or mechanical stress. During oxidation, the reactive material is a sensor of the ambient, the consumed electrical energy being the sensing magnitude. Devices based on any of the electrochemical properties of conducting polymers must act simultaneously as sensors of the working conditions. Artificial muscles, as electrochemical actuators constituted by reactive materials, respond to the ambient conditions during actuation. In this way, they can be used as actuators, sensing the surrounding conditions during actuation. Actuating and sensing signals are simultaneously included by the same two connecting wires. PMID- 22319266 TI - Development of X-Y servo pneumatic-piezoelectric hybrid actuators for position control with high response, large stroke and nanometer accuracy. AB - This study aims to develop a X-Y dual-axial intelligent servo pneumatic piezoelectric hybrid actuator for position control with high response, large stroke (250 mm, 200 mm) and nanometer accuracy (20 nm). In each axis, the rodless pneumatic actuator serves to position in coarse stroke and the piezoelectric actuator compensates in fine stroke. Thus, the overall control systems of the single axis become a dual-input single-output (DISO) system. Although the rodless pneumatic actuator has relatively larger friction force, it has the advantage of mechanism for multi-axial development. Thus, the X-Y dual-axial positioning system is developed based on the servo pneumatic-piezoelectric hybrid actuator. In addition, the decoupling self-organizing fuzzy sliding mode control is developed as the intelligent control strategies. Finally, the proposed novel intelligent X-Y dual-axial servo pneumatic-piezoelectric hybrid actuators are implemented and verified experimentally. PMID- 22319267 TI - Infrared spectroscopy on smoke produced by cauterization of animal tissue. AB - In view of in vivo surgical smoke studies a difference-frequency-generation (DFG) laser spectrometer (spectral range 2900-3144 cm(-1)) and a Fourier-transform infrared (FTIR) spectrometer were employed for infrared absorption spectroscopy. The chemical composition of smoke produced in vitro with an electroknife by cauterization of different animal tissues in different atmospheres was investigated. Average concentrations derived are: water vapor (0.87%), methane (20 ppm), ethane (4.8 ppm), ethene (17 ppm), carbon monoxide (190 ppm), nitric oxide (25 ppm), nitrous oxide (40 ppm), ethyne (50 ppm) and hydrogen cyanide (25 ppm). No correlation between smoke composition and the atmosphere or the kind of cauterized tissue was found. PMID- 22319268 TI - In/out status monitoring in mobile asset tracking with wireless sensor networks. AB - A mobile asset with a sensor node in a mobile asset tracking system moves around a monitoring area, leaves it, and then returns to the region repeatedly. The system monitors the in/out status of the mobile asset. Due to the continuous movement of the mobile asset, the system may generate an error for the in/out status of the mobile asset. When the mobile asset is inside the region, the system might determine that it is outside, or vice versa. In this paper, we propose a method to detect and correct the incorrect in/out status of the mobile asset. To solve this problem, our approach uses data about the connection state transition and the battery lifetime of the mobile node attached to the mobile asset. The connection state transition is used to classify the mobile node as normal or abnormal. The battery lifetime is used to predict a valid working period for the mobile node. We evaluate our method using real data generated by a medical asset tracking system. The experimental results show that our method, by using the estimated battery life time or by using the invalid connection state, can detect and correct most cases of incorrect in/out statuses generated by the conventional approach. PMID- 22319270 TI - A time tree medium access control for energy efficiency and collision avoidance in wireless sensor networks. AB - This paper presents a medium access control and scheduling scheme for wireless sensor networks. It uses time trees for sending data from the sensor node to the base station. For an energy efficient operation of the sensor networks in a distributed manner, time trees are built in order to reduce the collision probability and to minimize the total energy required to send data to the base station. A time tree is a data gathering tree where the base station is the root and each sensor node is either a relaying or a leaf node of the tree. Each tree operates in a different time schedule with possibly different activation rates. Through the simulation, the proposed scheme that uses time trees shows better characteristics toward burst traffic than the previous energy and data arrival rate scheme. PMID- 22319269 TI - Oxidant sensing by protein kinases a and g enables integration of cell redox state with phosphoregulation. AB - The control of vascular smooth muscle contractility enables regulation of blood pressure, which is paramount in physiological adaptation to environmental challenges. Maintenance of stable blood pressure is crucial for health as deregulation (caused by high or low blood pressure) leads to disease progression. Vasotone is principally controlled by the cyclic nucleotide dependent protein kinases A and G, which regulate intracellular calcium and contractile protein calcium sensitivity. The classical pathways for activation of these two kinases are well established and involve the formation and activation by specific cyclic nucleotide second messengers. Recently we reported that both PKA and PKG can be regulated independently of their respective cyclic nucleotides via a mechanism whereby the kinases sense cellular oxidant production using redox active thiols. This novel redox regulation of these kinases is potentially of physiological importance, and may synergise with the classical regulatory mechanisms. PMID- 22319271 TI - Acquiring authentic data in unattended wireless sensor networks. AB - An Unattended Wireless Sensor Network (UWSN) can be used in many applications to collect valuable data. Nevertheless, due to the unattended nature, the sensors could be compromised and the sensor readings would be maliciously altered so that the sink accepts the falsified sensor readings. Unfortunately, few attentions have been given to this authentication problem. Moreover, existing methods suffer from different kinds of DoS attacks such as Path-Based DoS (PDoS) and False Endorsement-based DoS (FEDoS) attacks. In this paper, a scheme, called AAD, is proposed to Acquire Authentic Data in UWSNs. We exploit the collaboration among sensors to address the authentication problem. With the proper design of the collaboration mechanism, AAD has superior resilience against sensor compromises, PDoS attack, and FEDoS attack. In addition, compared with prior works, AAD also has relatively low energy consumption. In particular, according to our simulation, in a network with 1,000 sensors, the energy consumed by AAD is lower than 30% of that consumed by the existing method, ExCo. The analysis and simulation are also conducted to demonstrate the superiority of the proposed AAD scheme over the existing methods. PMID- 22319272 TI - DRDT: distributed and reliable data transmission with cooperative nodes for lossy wireless sensor networks. AB - Recent studies have shown that in realistic wireless sensor network environments links are extremely unreliable. To recover from corrupted packets, most routing schemes with an assumption of ideal radio environments use a retransmission mechanism, which may cause unnecessary retransmissions. Therefore, guaranteeing energy-efficient reliable data transmission is a fundamental routing issue in wireless sensor networks. However, it is not encouraged to propose a new reliable routing scheme in the sense that every existing routing scheme cannot be replaced with the new one. This paper proposes a Distributed and Reliable Data Transmission (DRDT) scheme with a goal to efficiently guarantee reliable data transmission. In particular, this is based on a pluggable modular approach so that it can be extended to existing routing schemes. DRDT offers reliable data transmission using neighbor nodes, i.e., helper nodes. A helper node is selected among the neighbor nodes of the receiver node which overhear the data packet in a distributed manner. DRDT effectively reduces the number of retransmissions by delegating the retransmission task from the sender node to the helper node that has higher link quality to the receiver node when the data packet reception fails due to the low link quality between the sender and the receiver nodes. Comprehensive simulation results show that DRDT improves end-to-end transmission cost by up to about 45% and reduces its delay by about 40% compared to existing schemes. PMID- 22319273 TI - Development of a chemiresistor sensor based on polymers-dye blend for detection of ethanol vapor. AB - The conductive blend of the poly (3,4-ethylene dioxythiophene) and polystyrene sulfonated acid (PEDOT-PSS) polymers were doped with Methyl Red (MR) dye in the acid form and were used as the basis for a chemiresistor sensor for detection of ethanol vapor. This Au | Polymers-dye blend | Au device was manufactured by chemical vapor deposition and spin-coating, the first for deposition of the metal electrodes onto a glass substrate, and the second for preparation of the organic thin film forming ~1.0 mm2 of active area. The results obtained are the following: (i) electrical resistance dependence with atmospheres containing ethanol vapor carried by nitrogen gas and humidity; (ii) sensitivity at 1.15 for limit detection of 26.25 ppm analyte and an operating temperature of 25 degrees C; and (iii) the sensing process is quickly reversible and shows very a low power consumption of 20 MUW. The thin film morphology of ~200 nm thickness was analyzed by Atomic Force Microscopy (AFM), where it was observed to have a peculiarly granulometric surface favorable to adsorption. This work indicates that PEDOT-PSS doped with MR dye to compose blend film shows good performance like resistive sensor. PMID- 22319274 TI - Performance analysis and improvement of WPAN MAC for home networks. AB - The wireless personal area network (WPAN) is an emerging wireless technology for future short range indoor and outdoor communication applications. The IEEE 802.15.3 medium access control (MAC) is proposed to coordinate the access to the wireless medium among the competing devices, especially for short range and high data rate applications in home networks. In this paper we use analytical modeling to study the performance analysis of WPAN (IEEE 802.15.3) MAC in terms of throughput, efficient bandwidth utilization, and delay with various ACK policies under error channel condition. This allows us to introduce a K-Dly-ACK-AGG policy, payload size adjustment mechanism, and Improved Backoff algorithm to improve the performance of the WPAN MAC. Performance evaluation results demonstrate the impact of our improvements on network capacity. Moreover, these results can be very useful to WPAN application designers and protocol architects to easily and correctly implement WPAN for home networking. PMID- 22319275 TI - Active ground optical remote sensing for improved monitoring of seedling stress in nurseries. AB - Active ground optical remote sensing (AGORS) devices mounted on overhead irrigation booms could help to improve seedling quality by autonomously monitoring seedling stress. In contrast to traditionally used passive optical sensors, AGORS devices operate independently of ambient light conditions and do not require spectral reference readings. Besides measuring red (590-670 nm) and near-infrared (>760 nm) reflectance AGORS devices have recently become available that also measure red-edge (730 nm) reflectance. We tested the hypothesis that the additional availability of red-edge reflectance information would improve AGORS of plant stress induced chlorophyll breakdown in Scots pine (Pinus sylvestris). Our results showed that the availability of red-edge reflectance information improved AGORS estimates of stress induced variation in chlorophyll concentration (r2>0.73, RMSE<1.69) when compared to those without (r2=0.57, RMSE=2.11). PMID- 22319276 TI - Galvanostatic entrapment of penicillinase into polytyramine films and its utilization for the potentiometric determination of penicillin. AB - A sensitive and reliable potentiometric biosensor for determination of penicillin has been developed by exploiting the self-limiting growth of the non-conducting polymer, polytyramine. Optimum polytyramine-penicillinase (PTy-PNCnase) films for potentiometric detection of penicillin were accomplished with monomer solutions which contained 0.03 M tyramine, 37 U/mL penicillinase, 0.01 M KNO3, and 3 mM penicillin with an applied current density of 0.8 mA/cm2 and an electropolymerisation time of 40 seconds. The potentiometric biosensor gave a linear concentration range of 3-283 MUM for penicillin and achieved a minimum detectable concentration of 0.3 MUM. The biosensor was successfully utilized for the detection of Amoxycillin and gave an average percentage recovery of 102+/-6%. Satisfactory recoveries of penicillin G were also achieved in milk samples with the potentiometric biosensor when concentrations are >=20 ppm. PMID- 22319277 TI - Discriminant analysis of Raman spectra for body fluid identification for forensic purposes. AB - Detection and identification of blood, semen and saliva stains, the most common body fluids encountered at a crime scene, are very important aspects of forensic science today. This study targets the development of a nondestructive, confirmatory method for body fluid identification based on Raman spectroscopy coupled with advanced statistical analysis. Dry traces of blood, semen and saliva obtained from multiple donors were probed using a confocal Raman microscope with a 785-nm excitation wavelength under controlled laboratory conditions. Results demonstrated the capability of Raman spectroscopy to identify an unknown substance to be semen, blood or saliva with high confidence. PMID- 22319278 TI - Real-time occlusion handling in augmented reality based on an object tracking approach. AB - To produce a realistic augmentation in Augmented Reality, the correct relative positions of real objects and virtual objects are very important. In this paper, we propose a novel real-time occlusion handling method based on an object tracking approach. Our method is divided into three steps: selection of the occluding object, object tracking and occlusion handling. The user selects the occluding object using an interactive segmentation method. The contour of the selected object is then tracked in the subsequent frames in real-time. In the occlusion handling step, all the pixels on the tracked object are redrawn on the unprocessed augmented image to produce a new synthesized image in which the relative position between the real and virtual object is correct. The proposed method has several advantages. First, it is robust and stable, since it remains effective when the camera is moved through large changes of viewing angles and volumes or when the object and the background have similar colors. Second, it is fast, since the real object can be tracked in real-time. Last, a smoothing technique provides seamless merging between the augmented and virtual object. Several experiments are provided to validate the performance of the proposed method. PMID- 22319279 TI - Investigation on reliability and scalability of an FBG-based hierarchical AOFSN. AB - The reliability and scalability of large-scale based optical fiber sensor networks (AOFSN) are considered in this paper. The AOFSN network consists of three-level hierarchical sensor network architectures. The first two levels consist of active interrogation and remote nodes (RNs) and the third level, called the sensor subnet (SSN), consists of passive Fiber Bragg Gratings (FBGs) and a few switches. The switch architectures in the RN and various SSNs to improve the reliability and scalability of AOFSN are studied. Two SSNs with a regular topology are proposed to support simple routing and scalability in AOFSN: square-based sensor cells (SSC) and pentagon-based sensor cells (PSC). The reliability and scalability are evaluated in terms of the available sensing coverage in the case of one or multiple link failures. PMID- 22319280 TI - Adaptive-compression based congestion control technique for wireless sensor networks. AB - Congestion in a wireless sensor network causes an increase in the amount of data loss and delays in data transmission. In this paper, we propose a new congestion control technique (ACT, Adaptive Compression-based congestion control Technique) based on an adaptive compression scheme for packet reduction in case of congestion. The compression techniques used in the ACT are Discrete Wavelet Transform (DWT), Adaptive Differential Pulse Code Modulation (ADPCM), and Run Length Coding (RLC). The ACT first transforms the data from the time domain to the frequency domain, reduces the range of data by using ADPCM, and then reduces the number of packets with the help of RLC before transferring the data to the source node. It introduces the DWT for priority-based congestion control because the DWT classifies the data into four groups with different frequencies. The ACT assigns priorities to these data groups in an inverse proportion to the respective frequencies of the data groups and defines the quantization step size of ADPCM in an inverse proportion to the priorities. RLC generates a smaller number of packets for a data group with a low priority. In the relaying node, the ACT reduces the amount of packets by increasing the quantization step size of ADPCM in case of congestion. Moreover, in order to facilitate the back pressure, the queue is controlled adaptively according to the congestion state. We experimentally demonstrate that the ACT increases the network efficiency and guarantees fairness to sensor nodes, as compared with the existing methods. Moreover, it exhibits a very high ratio of the available data in the sink. PMID- 22319281 TI - Dynamic characteristics of a hydraulic amplification mechanism for large displacement actuators systems. AB - We have developed a hydraulic displacement amplification mechanism (HDAM) and studied its dynamic response when combined with a piezoelectric actuator. The HDAM consists of an incompressible fluid sealed in a microcavity by two largely deformable polydimethylsiloxane (PDMS) membranes. The geometry with input and output surfaces having different cross-sectional areas creates amplification. By combining the HDAM with micro-actuators, we can amplify the input displacement generated by the actuators, which is useful for applications requiring large deformation, such as tactile displays. We achieved a mechanism offering up to 18 fold displacement amplification for static actuation and 12-fold for 55 Hz dynamic actuation. PMID- 22319282 TI - Development of an indoor location based service test bed and geographic information system with a wireless sensor network. AB - In order to provide the seamless navigation and positioning services for indoor environments, an indoor location based service (LBS) test bed is developed to integrate the indoor positioning system and the indoor three-dimensional (3D) geographic information system (GIS). A wireless sensor network (WSN) is used in the developed indoor positioning system. Considering the power consumption, in this paper the ZigBee radio is used as the wireless protocol, and the received signal strength (RSS) fingerprinting positioning method is applied as the primary indoor positioning algorithm. The matching processes of the user location include the nearest neighbor (NN) algorithm, the K-weighted nearest neighbors (KWNN) algorithm, and the probabilistic approach. To enhance the positioning accuracy for the dynamic user, the particle filter is used to improve the positioning performance. As part of this research, a 3D indoor GIS is developed to be used with the indoor positioning system. This involved using the computer-aided design (CAD) software and the virtual reality markup language (VRML) to implement a prototype indoor LBS test bed. Thus, a rapid and practical procedure for constructing a 3D indoor GIS is proposed, and this GIS is easy to update and maintenance for users. The building of the Department of Aeronautics and Astronautics at National Cheng Kung University in Taiwan is used as an example to assess the performance of various algorithms for the indoor positioning system. PMID- 22319283 TI - Optical flow in a smart sensor based on hybrid analog-digital architecture. AB - The purpose of this study is to develop a motion sensor (delivering optical flow estimations) using a platform that includes the sensor itself, focal plane processing resources, and co-processing resources on a general purpose embedded processor. All this is implemented on a single device as a SoC (System-on-a Chip). Optical flow is the 2-D projection into the camera plane of the 3-D motion information presented at the world scenario. This motion representation is widespread well-known and applied in the science community to solve a wide variety of problems. Most applications based on motion estimation require work in real-time; hence, this restriction must be taken into account. In this paper, we show an efficient approach to estimate the motion velocity vectors with an architecture based on a focal plane processor combined on-chip with a 32 bits NIOS II processor. Our approach relies on the simplification of the original optical flow model and its efficient implementation in a platform that combines an analog (focal-plane) and digital (NIOS II) processor. The system is fully functional and is organized in different stages where the early processing (focal plane) stage is mainly focus to pre-process the input image stream to reduce the computational cost in the post-processing (NIOS II) stage. We present the employed co-design techniques and analyze this novel architecture. We evaluate the system's performance and accuracy with respect to the different proposed approaches described in the literature. We also discuss the advantages of the proposed approach as well as the degree of efficiency which can be obtained from the focal plane processing capabilities of the system. The final outcome is a low cost smart sensor for optical flow computation with real-time performance and reduced power consumption that can be used for very diverse application domains. PMID- 22319284 TI - Implementation and evaluation of the WADGPS system in the Taipei Flight Information Region. AB - This paper describes the implementation of the Wide Area Differential Global Positioning System (WADGPS) system in order to evaluate the operational performance of a satellite based aviation navigation system within Taipei Flight Information Region (FIR). The main objective of the WADGPS is to provide real time integrity information regarding the use of GPS for civil aviation applications. This paper uses the e-GPS observation stations operated by the Taiwan Ministry of Interior (MOI) as the WADGPS reference stations to collect the L1-L2 dual-frequency GPS measurements. A WADGPS master station is also implemented to process all GPS measurements sent from each reference station, and then generate the vector corrections. These vector corrections consist of the satellite ephemeris and clock errors, and a grid of ionospheric delays. The data stream also includes confidence bounds for the corrections and "Use/Do Not Use" messages to provide integrity. These messages are then passed to the WADGPS user through the Internet. This paper discusses the WADGPS system architecture and the system performance analysis. A five-day operation performance in Taipei Flight Information Region (FIR) is presented in this paper. The results show that the WADGPS can improve the accuracy performance of GPS positioning and fulfill the integrity performance required by Non-Precision Approach (NPA) defined by the International Civil Aviation Organization (ICAO). PMID- 22319285 TI - Data centric storage technologies: analysis and enhancement. AB - This paper surveys the most relevant works of Data Centric Storage (DCS) for Wireless Sensor Networks. DCS is a research area that covers data dissemination and storage inside an ad-hoc sensor network. In addition, we present a Quadratic Adaptive Replication (QAR) scheme for DCS, which is a more adaptive multi replication DCS system and outperforms previous proposals in the literature by reducing the overall network traffic that has a direct impact on energy consumption. Finally, we discuss the open research challenges for DCS. PMID- 22319286 TI - The assessment for sensitivity of a NO2 gas sensor with ZnGa2O4/ZnO core-shell nanowires--a novel approach. AB - The application of novel core-shell nanowires composed of ZnGa2O4/ZnO to improve the sensitivity of NO2 gas sensors is demonstrated in this study. The growth of ZnGa2O4/ZnO core-shell nanowires is performed by reactive evaporation on patterned ZnO:Ga/SiO2/Si templates at 600 degrees C. This is to form the homogeneous structure of the sensors investigated in this report to assess their sensitivity in terms of NO2 detection. These novel NO2 gas sensors were evaluated at working temperatures of 25 degrees C and at 250 degrees C, respectively. The result reveals the ZnGa2O4/ZnO core-shell nanowires present a good linear relationship (R2>0.99) between sensitivity and NO2 concentration at both working temperatures. These core-shell nanowire sensors also possess the highest response (<90 s) and recovery (<120 s) values with greater repeatability seen for NO2 sensors at room temperature, unlike traditional sensors that only work effectively at much higher temperatures. The data in this study indicates the newly-developed ZnGa2O4/ZnO core-shell nanowire based sensors are highly promising for industrial applications. PMID- 22319287 TI - Evaluation of performance and uncertainty of infrared tympanic thermometers. AB - Infrared tympanic thermometers (ITTs) are easy to use and have a quick response time. They are widely used for temperature measurement of the human body. The accuracy and uncertainty of measurement is the importance performance indicator for these meters. The performance of two infrared tympanic thermometers, Braun THT-3020 and OMRON MC-510, were evaluated in this study. The cell of a temperature calibrator was modified to serve as the standard temperature of the blackbody. The errors of measurement for the two meters were reduced by the calibration equation. The predictive values could meet the requirements of the ASTM standard. The sources of uncertainty include the standard deviations of replication at fixed temperature or the predicted values of calibration equation, reference standard values and resolution. The uncertainty analysis shows that the uncertainty of calibration equation is the main source for combined uncertainty. Ambient temperature did not have the significant effects on the measured performance. The calibration equations could improve the accuracy of ITTs. However, these equations did not improve the uncertainty of ITTs. PMID- 22319288 TI - Design and instrumentation of a measurement and calibration system for an acoustic telemetry system. AB - The Juvenile Salmon Acoustic Telemetry System (JSATS) is an active sensing technology developed by the U.S. Army Corps of Engineers, Portland District, for detecting and tracking small fish. It is used primarily for evaluating behavior and survival of juvenile salmonids migrating through the Federal Columbia River Power System to the Pacific Ocean. It provides critical data for salmon protection and development of more "fish-friendly" hydroelectric facilities. The objective of this study was to design and build a Measurement and Calibration System (MCS) for evaluating the JSATS components, because the JSATS requires comprehensive acceptance and performance testing in a controlled environment before it is deployed in the field. The MCS consists of a reference transducer, a water test tank lined with anechoic material, a motion control unit, a reference receiver, a signal conditioner and amplifier unit, a data acquisition board, MATLAB control and analysis interface, and a computer. The fully integrated MCS has been evaluated successfully at various simulated distances and using different encoded signals at frequencies within the bandwidth of the JSATS transmitter. The MCS provides accurate acoustic mapping capability in a controlled environment and automates the process that allows real-time measurements and evaluation of the piezoelectric transducers, sensors, or the acoustic fields. The MCS has been in use since 2009 for acceptance and performance testing of, and further improvements to, the JSATS. PMID- 22319289 TI - Energy-aware scheduling of surveillance in wireless multimedia sensor networks. AB - Wireless sensor networks involve a large number of sensor nodes with limited energy supply, which impacts the behavior of their application. In wireless multimedia sensor networks, sensor nodes are equipped with audio and visual information collection modules. Multimedia contents are ubiquitously retrieved in surveillance applications. To solve the energy problems during target surveillance with wireless multimedia sensor networks, an energy-aware sensor scheduling method is proposed in this paper. Sensor nodes which acquire acoustic signals are deployed randomly in the sensing fields. Target localization is based on the signal energy feature provided by multiple sensor nodes, employing particle swarm optimization (PSO). During the target surveillance procedure, sensor nodes are adaptively grouped in a totally distributed manner. Specially, the target motion information is extracted by a forecasting algorithm, which is based on the hidden Markov model (HMM). The forecasting results are utilized to awaken sensor node in the vicinity of future target position. According to the two properties, signal energy feature and residual energy, the sensor nodes decide whether to participate in target detection separately with a fuzzy control approach. Meanwhile, the local routing scheme of data transmission towards the observer is discussed. Experimental results demonstrate the efficiency of energy aware scheduling of surveillance in wireless multimedia sensor network, where significant energy saving is achieved by the sensor awakening approach and data transmission paths are calculated with low computational complexity. PMID- 22319291 TI - A method for clustering and cooperation in wireless multimedia sensor networks. AB - Wireless multimedia sensor nodes sense areas that are uncorrelated to the areas covered by radio neighbouring sensors. Thus, node clustering for coordinating multimedia sensing and processing cannot be based on classical sensor clustering algorithms. This paper presents a clustering mechanism for Wireless Multimedia Sensor Networks (WMSNs) based on overlapped Field of View (FoV) areas. Overlapping FoVs in dense networks cause the wasting of power due to redundant area sensing. The main aim of the proposed clustering method is energy conservation and network lifetime prolongation. This objective is achieved through coordination of nodes belonging to the same cluster to perform assigned tasks in a cooperative manner avoiding redundant sensing or processing. A paradigm in this concept, a cooperative scheduling scheme for object detection, is presented based on the proposed clustering method. PMID- 22319290 TI - Environmentally sensitive fluorescent sensors based on synthetic peptides. AB - Biosensors allow the direct detection of molecular analytes, by associating a biological receptor with a transducer able to convert the analyte-receptor recognition event into a measurable signal. We review recent work aimed at developing synthetic fluorescent molecular sensors for a variety of analytes, based on peptidic receptors labeled with environmentally sensitive fluorophores. Fluorescent indicators based on synthetic peptides are highly interesting alternatives to protein-based sensors, since they can be synthesized chemically, are stable, and can be easily modified in a site-specific manner for fluorophore coupling and for immobilization on solid supports. PMID- 22319292 TI - Novel anti co-channel interference scheme for sensor networks. AB - With improvement of the automation level, wireless sensors are widely used, but various kinds of interference lead to problems in the application. In order to deal with co-channel interference, a throughput efficient scheme based on Extended Binary Phase Shift Keying (EBPSK) modulation is introduced in physical layer. On this basis, the corresponding transmission scheme and the important impacting filter are presented. Effects of co-channel interference on the EBPSK waveform in different cases are analyzed. Simulation results illustrate the excellent anti-interference performance of the EBPSK system itself, when the initial phase of the co-channel interference is small. PMID- 22319293 TI - A new myohaptic instrument to assess wrist motion dynamically. AB - The pathophysiological assessment of joint properties and voluntary motion in neurological patients remains a challenge. This is typically the case in cerebellar patients, who exhibit dysmetric movements due to the dysfunction of cerebellar circuitry. Several tools have been developed, but so far most of these tools have remained confined to laboratories, with a lack of standardization. We report on a new device which combines the use of electromyographic (EMG) sensors with haptic technology for the dynamic investigation of wrist properties. The instrument is composed of a drivetrain, a haptic controller and a signal acquisition unit. Angular accuracy is 0.00611 rad, nominal torque is 6 N.m, maximal rotation velocity is 34.907 rad/sec, with a range of motion of -1.0472 to +1.0472 rad. The inertia of the motor and handgrip is 0.004 kg.m2. This is the first standardized myohaptic instrument allowing the dynamic characterization of wrist properties, including under the condition of artificial damping. We show that cerebellar patients are unable to adapt EMG activities when faced with an increase in damping while performing fast reversal movements. The instrument allows the extraction of an electrophysiological signature of a cerebellar deficit. PMID- 22319294 TI - Evaluation of tunable data compression in energy-aware wireless sensor networks. AB - Energy is an important consideration in wireless sensor networks. In the current compression evaluations, traditional indices are still used, while energy efficiency is probably neglected. Moreover, various evaluation biases significantly affect the final results. All these factors lead to a subjective evaluation. In this paper, a new criterion is proposed and a series of tunable compression algorithms are reevaluated. The results show that the new criterion makes the evaluation more objective. Additionally it indicates the situations when compression is unnecessary. A new adaptive compression arbitration system is proposed based on the evaluation results, which improves the performance of compression algorithms. PMID- 22319296 TI - Wireless health data exchange for home healthcare monitoring systems. AB - Ubiquitous home healthcare systems have been playing an increasingly significant role in the treatment and management of chronic diseases, such as diabetes and hypertension, but progress has been hampered by the lack of standardization in the exchange of medical health care information. In an effort to establish standardization, this paper proposes a home healthcare monitoring system data exchange scheme between the HL7 standard and the IEEE1451 standard. IEEE1451 is a standard for special sensor networks, such as industrial control and smart homes, and defines a suite of interfaces that communicate among heterogeneous networks. HL7 is the standard for medical information exchange among medical organizations and medical personnel. While it provides a flexible data exchange in health care domains, it does not provide for data exchange with sensors. Thus, it is necessary to develop a data exchange schema to convert data between the HL7 and the IEEE1451 standard. This paper proposes a schema that can exchange data between HL7 devices and the monitoring device, and conforms to the IEEE 1451 standard. The experimental results and conclusions of this approach are presented and show the feasibility of the proposed exchange schema. PMID- 22319295 TI - Visual pathways serving motion detection in the mammalian brain. AB - Motion perception is the process through which one gathers information on the dynamic visual world, in terms of the speed and movement direction of its elements. Motion sensation takes place from the retinal light sensitive elements, through the visual thalamus, the primary and higher visual cortices. In the present review we aim to focus on the extrageniculo-extrastriate cortical and subcortical visual structures of the feline and macaque brain and discuss their functional role in visual motion perception. Special attention is paid to the ascending tectofugal system that may serve for detection of the visual environment during self-motion. PMID- 22319297 TI - Multi-camera sensor system for 3D segmentation and localization of multiple mobile robots. AB - This paper presents a method for obtaining the motion segmentation and 3D localization of multiple mobile robots in an intelligent space using a multi camera sensor system. The set of calibrated and synchronized cameras are placed in fixed positions within the environment (intelligent space). The proposed algorithm for motion segmentation and 3D localization is based on the minimization of an objective function. This function includes information from all the cameras, and it does not rely on previous knowledge or invasive landmarks on board the robots. The proposed objective function depends on three groups of variables: the segmentation boundaries, the motion parameters and the depth. For the objective function minimization, we use a greedy iterative algorithm with three steps that, after initialization of segmentation boundaries and depth, are repeated until convergence. PMID- 22319298 TI - GFZ wireless seismic array (GFZ-WISE), a wireless mesh network of seismic sensors: new perspectives for seismic noise array investigations and site monitoring. AB - Over the last few years, the analysis of seismic noise recorded by two dimensional arrays has been confirmed to be capable of deriving the subsoil shear wave velocity structure down to several hundred meters depth. In fact, using just a few minutes of seismic noise recordings and combining this with the well known horizontal-to-vertical method, it has also been shown that it is possible to investigate the average one dimensional velocity structure below an array of stations in urban areas with a sufficient resolution to depths that would be prohibitive with active source array surveys, while in addition reducing the number of boreholes required to be drilled for site-effect analysis. However, the high cost of standard seismological instrumentation limits the number of sensors generally available for two-dimensional array measurements (i.e., of the order of 10), limiting the resolution in the estimated shear-wave velocity profiles. Therefore, new themes in site-effect estimation research by two-dimensional arrays involve the development and application of low-cost instrumentation, which potentially allows the performance of dense-array measurements, and the development of dedicated signal-analysis procedures for rapid and robust estimation of shear-wave velocity profiles. In this work, we present novel low cost wireless instrumentation for dense two-dimensional ambient seismic noise array measurements that allows the real-time analysis of the surface-wavefield and the rapid estimation of the local shear-wave velocity structure for site response studies. We first introduce the general philosophy of the new system, as well as the hardware and software that forms the novel instrument, which we have tested in laboratory and field studies. PMID- 22319299 TI - Laser photoacoustic detection of CO2 in old disc tree-rings. AB - A homemade CO2-laser photoacoustic spectrometer has been used for monitoring CO2 in gas samples extracted under vacuum from the wood of old spruce disc tree-rings for a ~60 year series. The experimental results show that (1) the CO2 concentration exhibits annual trends correlated with an increase in atmospheric CO2 in a number of cases; (2) at the time when the annual CO2 trend changes from positive to negative, the annual tree-ring stable carbon isotope ratios (delta13C) of CO2 change as well; (3) the disc tree-ring widths are observed to decrease in most cases where the annual CO2 increased; (4) simultaneously with the annual CO2 variation, annual H2O distribution was detected in gas samples of the wood tree-rings of one spruce disc. The observed patterns of the annual CO2 distribution in the disc tree-rings are assumed to be the evidence of the impact of the atmospheric CO2 increase. In other words, a change in the concentration gradient between the stem and the atmospheric CO2 may lead to a gradual CO2 accumulation in the stem because of a decrease in the diffusion rate and to a change in the tree parameters. PMID- 22319300 TI - A FDR sensor for measuring complex soil dielectric permittivity in the 10-500 MHz frequency range. AB - Mechanical details as well as electrical models of FDR (frequency domain reflectometry) sensors for the measurement of the complex dielectric permittivity of porous materials are presented. The sensors are formed from two stainless steel parallel waveguides of various lengths. Using the data from VNA (vector network analyzer) with the connected FDR sensor and selected models of the applied sensor it was possible obtain the frequency spectrum of dielectric permittivity from 10 to 500 MHz of reference liquids and soil samples of various moisture and salinity. The performance of the analyzed sensors were compared with TDR (time domain reflectometry) ones of similar mechanical construction. PMID- 22319301 TI - Optimal filters with multiple packet losses and its application in wireless sensor networks. AB - This paper is concerned with the filtering problem for both discrete-time stochastic linear (DTSL) systems and discrete-time stochastic nonlinear (DTSN) systems. In DTSL systems, an linear optimal filter with multiple packet losses is designed based on the orthogonal principle analysis approach over unreliable wireless sensor networks (WSNs), and the experience result verifies feasibility and effectiveness of the proposed linear filter; in DTSN systems, an extended minimum variance filter with multiple packet losses is derived, and the filter is extended to the nonlinear case by the first order Taylor series approximation, which is successfully applied to unreliable WSNs. An application example is given and the corresponding simulation results show that, compared with extended Kalman filter (EKF), the proposed extended minimum variance filter is feasible and effective in WSNs. PMID- 22319302 TI - Multiplexed electrochemical detection of Yersinia pestis and staphylococcal enterotoxin B using an antibody microarray. AB - The CombiMatrix antibody microarray is a versatile, sensitive detection platform based on the generation and transduction of electrochemical signals following antigen binding to surface antibodies. The sensor chip described herein is comprised of microelectrodes coupled to an adjacent bio-friendly matrix coated with antibodies to the biological pathogens Yersinia pestis and Bacillus anthracis, and the bacterial toxin staphylococcal enterotoxin B (SEB). Using this system, we were able to detect SEB and inactivated Y. pestis individually as well as in two-plex assays at concentrations as low as 5 pg/mL and 10(6) CFU/mL, respectively. We also introduce super avidin-biotin system (SABS) as a viable and effective means to enhance assay signal responses and lower detection limits. Together these technologies represent substantial advances in point-of-care and point-of-use detection applications. PMID- 22319303 TI - Sensor fabrication method for in situ temperature and humidity monitoring of light emitting diodes. AB - In this work micro temperature and humidity sensors are fabricated to measure the junction temperature and humidity of light emitting diodes (LED). The junction temperature is frequently measured using thermal resistance measurement technology. The weakness of this method is that the timing of data capture is not regulated by any standard. This investigation develops a device that can stably and continually measure temperature and humidity. The device is light-weight and can monitor junction temperature and humidity in real time. Using micro-electro mechanical systems (MEMS), this study minimizes the size of the micro temperature and humidity sensors, which are constructed on a stainless steel foil substrate (40 MUm-thick SS-304). The micro temperature and humidity sensors can be fixed between the LED chip and frame. The sensitivities of the micro temperature and humidity sensors are 0.06+/-0.005 (Omega/ degrees C) and 0.033 pF/%RH, respectively. PMID- 22319304 TI - FPGA-based fused smart-sensor for tool-wear area quantitative estimation in CNC machine inserts. AB - Manufacturing processes are of great relevance nowadays, when there is a constant claim for better productivity with high quality at low cost. The contribution of this work is the development of a fused smart-sensor, based on FPGA to improve the online quantitative estimation of flank-wear area in CNC machine inserts from the information provided by two primary sensors: the monitoring current output of a servoamplifier, and a 3-axis accelerometer. Results from experimentation show that the fusion of both parameters makes it possible to obtain three times better accuracy when compared with the accuracy obtained from current and vibration signals, individually used. PMID- 22319305 TI - Speedy routing recovery protocol for large failure tolerance in wireless sensor networks. AB - Wireless sensor networks are expected to play an increasingly important role in data collection in hazardous areas. However, the physical fragility of a sensor node makes reliable routing in hazardous areas a challenging problem. Because several sensor nodes in a hazardous area could be damaged simultaneously, the network should be able to recover routing after node failures over large areas. Many routing protocols take single-node failure recovery into account, but it is difficult for these protocols to recover the routing after large-scale failures. In this paper, we propose a routing protocol, referred to as ARF (Adaptive routing protocol for fast Recovery from large-scale Failure), to recover a network quickly after failures over large areas. ARF detects failures by counting the packet losses from parent nodes, and upon failure detection, it decreases the routing interval to notify the neighbor nodes of the failure. Our experimental results indicate that ARF could provide recovery from large-area failures quickly with less packets and energy consumption than previous protocols. PMID- 22319306 TI - Advanced taste sensors based on artificial lipids with global selectivity to basic taste qualities and high correlation to sensory scores. AB - Effective R&D and strict quality control of a broad range of foods, beverages, and pharmaceutical products require objective taste evaluation. Advanced taste sensors using artificial-lipid membranes have been developed based on concepts of global selectivity and high correlation with human sensory score. These sensors respond similarly to similar basic tastes, which they quantify with high correlations to sensory score. Using these unique properties, these sensors can quantify the basic tastes of saltiness, sourness, bitterness, umami, astringency and richness without multivariate analysis or artificial neural networks. This review describes all aspects of these taste sensors based on artificial lipid, ranging from the response principle and optimal design methods to applications in the food, beverage, and pharmaceutical markets. PMID- 22319307 TI - Information warfare-worthy jamming attack detection mechanism for wireless sensor networks using a fuzzy inference system. AB - The proposed mechanism for jamming attack detection for wireless sensor networks is novel in three respects: firstly, it upgrades the jammer to include versatile military jammers; secondly, it graduates from the existing node-centric detection system to the network-centric system making it robust and economical at the nodes, and thirdly, it tackles the problem through fuzzy inference system, as the decision regarding intensity of jamming is seldom crisp. The system with its high robustness, ability to grade nodes with jamming indices, and its true-detection rate as high as 99.8%, is worthy of consideration for information warfare defense purposes. PMID- 22319308 TI - Webcams for bird detection and monitoring: a demonstration study. AB - Better insights into bird migration can be a tool for assessing the spread of avian borne infections or ecological/climatologic issues reflected in deviating migration patterns. This paper evaluates whether low budget permanent cameras such as webcams can offer a valuable contribution to the reporting of migratory birds. An experimental design was set up to study the detection capability using objects of different size, color and velocity. The results of the experiment revealed the minimum size, maximum velocity and contrast of the objects required for detection by a standard webcam. Furthermore, a modular processing scheme was proposed to track and follow migratory birds in webcam recordings. Techniques such as motion detection by background subtraction, stereo vision and lens distortion were combined to form the foundation of the bird tracking algorithm. Additional research to integrate webcam networks, however, is needed and future research should enforce the potential of the processing scheme by exploring and testing alternatives of each individual module or processing step. PMID- 22319309 TI - Levelling profiles and a GPS network to monitor the active folding and faulting deformation in the Campo de Dalias (Betic Cordillera, southeastern Spain). AB - The Campo de Dalias is an area with relevant seismicity associated to the active tectonic deformations of the southern boundary of the Betic Cordillera. A non permanent GPS network was installed to monitor, for the first time, the fault- and fold-related activity. In addition, two high precision levelling profiles were measured twice over a one-year period across the Balanegra Fault, one of the most active faults recognized in the area. The absence of significant movement of the main fault surface suggests seismogenic behaviour. The possible recurrence interval may be between 100 and 300 y. The repetitive GPS and high precision levelling monitoring of the fault surface during a long time period may help us to determine future fault behaviour with regard to the existence (or not) of a creep component, the accumulation of elastic deformation before faulting, and implications of the fold-fault relationship. PMID- 22319310 TI - Structures and encapsulation motifs of functional molecules probed by laser spectroscopic and theoretical methods. AB - We report laser spectroscopic and computational studies of host/guest hydration interactions between functional molecules (hosts) and water (guest) in supersonic jets. The examined hosts include dibenzo-18-crown-6-ether (DB18C6), benzo-18 crown-6-ether (B18C6) and calix[4]arene (C4A). The gaseous complexes between the functional molecular hosts and water are generated under jet-cooled conditions. Various laser spectroscopic methods are applied for these species: the electronic spectra are observed by laser-induced fluorescence (LIF), mass-selected resonance enhanced multiphoton ionization (REMPI) and ultraviolet-ultraviolet hole-burning (UV-UV HB) spectroscopy, whereas the vibrational spectra for each individual species are observed by infrared-ultraviolet double resonance (IR-UV DR) spectroscopy. The obained results are analyzed by first principles electronic structure calculations. We discuss the conformations of the host molecules, the structures of the complexes, and key interactions forming the specific complexes. PMID- 22319311 TI - Plasma plume oscillations monitoring during laser welding of stainless steel by discrete wavelet transform application. AB - The plasma optical radiation emitted during CO2 laser welding of stainless steel samples has been detected with a Si-PIN photodiode and analyzed under different process conditions. The discrete wavelet transform (DWT) has been used to decompose the optical signal into various discrete series of sequences over different frequency bands. The results show that changes of the process settings may yield different signal features in the range of frequencies between 200 Hz and 30 kHz. Potential applications of this method to monitor in real time the laser welding processes are also discussed. PMID- 22319312 TI - Potential for development of an Escherichia coli-based biosensor for assessing bioavailable methionine: a review. AB - Methionine is an essential amino acid for animals and is typically considered one of the first limiting amino acids in animal feed formulations. Methionine deficiency or excess in animal diets can lead to sub-optimal animal performance and increased environmental pollution, which necessitates its accurate quantification and proper dosage in animal rations. Animal bioassays are the current industry standard to quantify methionine bioavailability. However, animal based assays are not only time consuming, but expensive and are becoming more scrutinized by governmental regulations. In addition, a variety of artifacts can hinder the variability and time efficacy of these assays. Microbiological assays, which are based on a microbial response to external supplementation of a particular nutrient such as methionine, appear to be attractive potential alternatives to the already established standards. They are rapid and inexpensive in vitro assays which are characterized with relatively accurate and consistent estimation of digestible methionine in feeds and feed ingredients. The current review discusses the potential to develop Escherichia coli-based microbial biosensors for methionine bioavailability quantification. Methionine biosynthesis and regulation pathways are overviewed in relation to genetic manipulation required for the generation of a respective methionine auxotroph that could be practical for a routine bioassay. A prospective utilization of Escherichia coli methionine biosensor would allow for inexpensive and rapid methionine quantification and ultimately enable timely assessment of nutritional profiles of feedstuffs. PMID- 22319313 TI - Optical fiber LSPR biosensor prepared by gold nanoparticle assembly on polyelectrolyte multilayer. AB - This article provides a novel method of constructing an optical fiber localized surface plasmon resonance (LSPR) biosensor. A gold nanoparticle (NP) assembled film as the sensing layer was built on the polyelectrolyte (PE) multilayer modified sidewall of an unclad optical fiber. By using a trilayer PE structure, we obtained a monodisperse gold NP assembled film. The preparation procedure for this LSPR sensor is simple and time saving. The optical fiber LSPR sensor has higher sensitivity and outstanding reproducibility. The higher anti-interference ability for response to an antibody makes it a promising method in application as a portable immuno-sensor. PMID- 22319314 TI - Flexible temperature sensor array based on a graphite-polydimethylsiloxane composite. AB - This paper presents a novel method to fabricate temperature sensor arrays by dispensing a graphite-polydimethylsiloxane composite on flexible polyimide films. The fabricated temperature sensor array has 64 sensing cells in a 4*4 cm2 area. The sensor array can be used as humanoid artificial skin for sensation system of robots. Interdigitated copper electrodes were patterned on the flexible polyimide substrate for determining the resistivity change of the composites subjected to ambient temperature variations. Polydimethylsiloxane was used as the matrix. Composites of different graphite volume fractions for large dynamic range from 30 degrees C to 110 degrees C have been investigated. Our experiments showed that graphite powder provided the composite high temperature sensitivity. The fabricated temperature sensor array has been tested. The detected temperature contours are in good agreement with the shapes and magnitudes of different heat sources. PMID- 22319315 TI - Relaxation time estimation from complex magnetic resonance images. AB - Magnetic Resonance (MR) imaging techniques are used to measure biophysical properties of tissues. As clinical diagnoses are mainly based on the evaluation of contrast in MR images, relaxation times assume a fundamental role providing a major source of contrast. Moreover, they can give useful information in cancer diagnostic. In this paper we present a statistical technique to estimate relaxation times exploiting complex-valued MR images. Working in the complex domain instead of the amplitude one allows us to consider the data bivariate Gaussian distributed, and thus to implement a simple Least Square (LS) estimator on the available complex data. The proposed estimator results to be simple, accurate and unbiased. PMID- 22319316 TI - DMP: detouring using multiple paths against jamming attack for ubiquitous networking system. AB - To successfully realize the ubiquitous network environment including home automation or industrial control systems, it is important to be able to resist a jamming attack. This has recently been considered as an extremely threatening attack because it can collapse the entire network, despite the existence of basic security protocols such as encryption and authentication. In this paper, we present a method of jamming attack tolerant routing using multiple paths based on zones. The proposed scheme divides the network into zones, and manages the candidate forward nodes of neighbor zones. After detecting an attack, detour nodes decide zones for rerouting, and detour packets destined for victim nodes through forward nodes in the decided zones. Simulation results show that our scheme increases the PDR (Packet Delivery Ratio) and decreases the delay significantly in comparison with rerouting by a general routing protocol on sensor networks, AODV (Ad hoc On Demand Distance Vector), and a conventional JAM (Jammed Area Mapping) service with one reroute. PMID- 22319317 TI - A miniature system for separating aerosol particles and measuring mass concentrations. AB - We designed and fabricated a new sensing system which consists of two virtual impactors and two quartz-crystal microbalance (QCM) sensors for measuring particle mass concentration and size distribution. The virtual impactors utilized different inertial forces of particles in air flow to classify different particle sizes. They were designed to classify particle diameter, d, into three different ranges: d<2.28 MUm, 2.28 MUm<=d<=3.20 MUm, d>3.20 MUm. The QCM sensors were coated with a hydrogel, which was found to be a reliable adhesive for capturing aerosol particles. The QCM sensor coated with hydrogel was used to measure the mass loading of particles by utilizing its characteristic of resonant frequency shift. An integrated system has been demonstrated. PMID- 22319318 TI - Localization of mobile robots using odometry and an external vision sensor. AB - This paper presents a sensor system for robot localization based on the information obtained from a single camera attached in a fixed place external to the robot. Our approach firstly obtains the 3D geometrical model of the robot based on the projection of its natural appearance in the camera while the robot performs an initialization trajectory. This paper proposes a structure-from motion solution that uses the odometry sensors inside the robot as a metric reference. Secondly, an online localization method based on a sequential Bayesian inference is proposed, which uses the geometrical model of the robot as a link between image measurements and pose estimation. The online approach is resistant to hard occlusions and the experimental setup proposed in this paper shows its effectiveness in real situations. The proposed approach has many applications in both the industrial and service robot fields. PMID- 22319319 TI - Quantitative modeling of coupled piezo-elastodynamic behavior of piezoelectric actuators bonded to an elastic medium for structural health monitoring: a review. AB - Elastic waves, especially guided waves, generated by a piezoelectric actuator/sensor network, have shown great potential for on-line health monitoring of advanced aerospace, nuclear, and automotive structures in recent decades. Piezoelectric materials can function as both actuators and sensors in these applications due to wide bandwidth, quick response and low costs. One of the most fundamental issues surrounding the effective use of piezoelectric actuators is the quantitative evaluation of the resulting elastic wave propagation by considering the coupled piezo-elastodynamic behavior between the actuator and the host medium. Accurate characterization of the local interfacial stress distribution between the actuator and the host medium is the key issue for the problem. This paper presents a review of the development of analytical, numerical and hybrid approaches for modeling of the coupled piezo-elastodynamic behavior. The resulting elastic wave propagation for structural health monitoring is also summarized. PMID- 22319320 TI - A new automatic system for angular measurement and calibration in radiometric instruments. AB - This paper puts forward the design, construction and testing of a new automatic system for angular-response measurement and calibration in radiometric instruments. Its main characteristics include precision, speed, resolution, noise immunity, easy programming and operation. The developed system calculates the cosine error of the radiometer under test by means of a virtual instrument, from the measures it takes and through a mathematical procedure, thus allowing correcting the radiometer with the aim of preventing cosine error in its measurements. PMID- 22319321 TI - Authentication and key establishment in dynamic wireless sensor networks. AB - When a sensor node roams within a very large and distributed wireless sensor network, which consists of numerous sensor nodes, its routing path and neighborhood keep changing. In order to provide a high level of security in this environment, the moving sensor node needs to be authenticated to new neighboring nodes and a key established for secure communication. The paper proposes an efficient and scalable protocol to establish and update the authentication key in a dynamic wireless sensor network environment. The protocol guarantees that two sensor nodes share at least one key with probability 1 (100%) with less memory and energy cost, while not causing considerable communication overhead. PMID- 22319322 TI - A multiwell electrochemical biosensor for real-time monitoring of the behavioural changes of cells in vitro. AB - We report the development of a multiwell biosensor for detecting changes in the electrochemical open circuit potential (OCP) generated by viable human cells in vitro. The instrument features eight culture wells; each containing three gold sensors around a common silver/silver chloride reference electrode, prepared using screen-printed conductive inks. The potential applications of the device were demonstrated by monitoring rheumatoid synovial fibroblasts (RSF) and HepG2 hepatocarcinoma cells in response to chemical and biological treatments. This technology could provide an alternative to conventional end-point assays used in the fields of chemotherapy, toxicology and drug discovery. PMID- 22319323 TI - Error analysis in a stereo vision-based pedestrian detection sensor for collision avoidance applications. AB - This paper presents an analytical study of the depth estimation error of a stereo vision-based pedestrian detection sensor for automotive applications such as pedestrian collision avoidance and/or mitigation. The sensor comprises two synchronized and calibrated low-cost cameras. Pedestrians are detected by combining a 3D clustering method with Support Vector Machine-based (SVM) classification. The influence of the sensor parameters in the stereo quantization errors is analyzed in detail providing a point of reference for choosing the sensor setup according to the application requirements. The sensor is then validated in real experiments. Collision avoidance maneuvers by steering are carried out by manual driving. A real time kinematic differential global positioning system (RTK-DGPS) is used to provide ground truth data corresponding to both the pedestrian and the host vehicle locations. The performed field test provided encouraging results and proved the validity of the proposed sensor for being used in the automotive sector towards applications such as autonomous pedestrian collision avoidance. PMID- 22319324 TI - Development of an emergency locking unit for a belt-in-seat (BIS) system using a MEMS acceleration sensor. AB - This paper proposes an emergency locking unit (ELU) for a seat belt retractor which is mounted on the back frame of a vehicle seat. The proposed unit uses a recliner sensor based on a MEMS acceleration sensor and solenoid mechanism. The seat has an upper frame supported to tilt on a lower frame. The retractor in belt in seat (BIS) system is supported by the upper frame. The proposed recliner sensor based on a MEMS acceleration sensor comprises orientation means for maintaining a predetermined orientation of emergency relative to the lower frame independently of the force of gravity when the upper frame tilts on the lower frame. Experimental results show that the developed recliner sensor unit operates effectively with respect to rollover angles. Thus, the developed unit will have a considerable potential to offer a new design concept in BIS system. PMID- 22319325 TI - Optoelectronic capillary sensors in microfluidic and point-of-care instrumentation. AB - This paper presents a review, based on the published literature and on the authors' own research, of the current state of the art of fiber-optic capillary sensors and related instrumentation as well as their applications, with special emphasis on point-of-care chemical and biochemical sensors, systematizing the various types of sensors from the point of view of the principles of their construction and operation. Unlike classical fiber-optic sensors which rely on changes in light propagation inside the fiber as affected by outside conditions, optical capillary sensors rely on changes of light transmission in capillaries filled with the analyzed liquid, which opens the possibility of interesting new applications, while raising specific issues relating to the construction, materials and instrumentation of those sensors. PMID- 22319326 TI - Alternative sensor system and MLP neural network for vehicle pedal activity estimation. AB - It is accepted that the activity of the vehicle pedals (i.e., throttle, brake, clutch) reflects the driver's behavior, which is at least partially related to the fuel consumption and vehicle pollutant emissions. This paper presents a solution to estimate the driver activity regardless of the type, model, and year of fabrication of the vehicle. The solution is based on an alternative sensor system (regime engine, vehicle speed, frontal inclination and linear acceleration) that reflects the activity of the pedals in an indirect way, to estimate that activity by means of a multilayer perceptron neural network with a single hidden layer. PMID- 22319327 TI - Optical sensor for characterizing the phase transition in salted solutions. AB - We propose a new optical sensor to characterize the solid-liquid phase transition in salted solutions. The probe mainly consists of a Raman spectrometer that extracts the vibrational properties from the light scattered by the salty medium. The spectrum of the O-H stretching band was shown to be strongly affected by the introduction of NaCl and the temperature change as well. A parameter SD defined as the ratio of the integrated intensities of two parts of this band allows to study the temperature and concentration dependences of the phase transition. Then, an easy and efficient signal processing and the exploitation of a modified Boltzmann equation give information on the phase transition. Validations were done on solutions with varying concentration of NaCl. PMID- 22319328 TI - On BER performance of EBPSK-MODEM in AWGN channel. AB - In order to satisfy the higher and higher demand for communication systems, an Extended Binary Phase Shift Keying (EBPSK) system with very high spectra efficiency has been proposed. During the research, a special kind of filters was found, which can amplify the signal characteristics and remove utmost noise, i.e., at the point of the phase jumping corresponding to code "1", produce the amplitude impulse much higher than code "0", therefore, the aim of our study was to analyze the BER performance of the impacting filter assisted EBPSK-MODEM. Considering the receiver filtered "0" and "1"signal with Rice amplitude distribution, just having different mean values, so the BER performance of EBPSK is deduced based on the classic detection theory, and compared with the traditional BPSK modulation both in spectra efficiency and in BER performance, which lays the theoretical foundation for the feasibility of Ultra Narrow Band communications based on EBPSK modulation. PMID- 22319329 TI - Design, fabrication, and testing of a bulk micromachined inertial measurement unit. AB - A bulk micromachined inertial measurement unit (MIMU) is presented in this paper. Three single-axis accelerometers and three single-axis gyroscopes were simultaneously fabricated on a silicon wafer using a bulk micromachining process; the wafer is smaller than one square centimeter. In particular, a global area optimization method based on the relationship between the sensitivity and layout area was proposed to determine the layout configuration of the six sensors. The scale factors of the X/Y-axis accelerometer and Z-axis accelerometer are about 213.3 mV/g and 226.9 mV/g, respectively. The scale factors of the X/Y-axis gyroscope and Z-axis gyroscope are about 2.2 mV/ degrees /s and 10.8 mV/ degrees /s, respectively. The bias stability of the X/Y-axis gyroscope and the Z-axis gyroscope are about 2135 deg/h and 80 deg/h, respectively. Finally, the resolutions of X/Y-axis accelerometers, Z-axis accelerometers, X/Y-axis gyroscopes, and Z-axis gyroscopes are 0.0012 g/?Hz, 0.0011 g/?Hz, 0.314 degrees /s/?Hz, and 0.008 degrees /s/?Hz, respectively. PMID- 22319330 TI - Carbon nanotube integration with a CMOS process. AB - This work shows the integration of a sensor based on carbon nanotubes using CMOS technology. A chip sensor (CS) was designed and manufactured using a 0.30 MUm CMOS process, leaving a free window on the passivation layer that allowed the deposition of SWCNTs over the electrodes. We successfully investigated with the CS the effect of humidity and temperature on the electrical transport properties of SWCNTs. The possibility of a large scale integration of SWCNTs with CMOS process opens a new route in the design of more efficient, low cost sensors with high reproducibility in their manufacture. PMID- 22319331 TI - Spectroscopic interpretation of PAH-spectra in minerals and its possible application to soil monitoring. AB - In order to properly assess the feasibility of using Laser-Induced Fluorescence (LIF) spectroscopy for soil monitoring, the variation of fluorescence intensity due to the heterogeneity and complexity of soil media was investigated. Different soil minerals showed fluorescence spectral structures distinguishable from the contaminants, implying dissimilar interactions or the binding of contaminants on mineral surfaces. More interestingly, solvent and water addition showed different responses in the fluorescence spectral structure showing their effect on the interactions between contaminants and minerals. These results support the claim that the spectral structure contains information on contaminant-mineral interactions; therefore contaminants can be used as a fluorescence probe for these interactions. PMID- 22319332 TI - Metal oxide sensors for electronic noses and their application to food analysis. AB - Electronic noses (E-noses) use various types of electronic gas sensors that have partial specificity. This review focuses on commercial and experimental E-noses that use metal oxide semi-conductors. The review covers quality control applications to food and beverages, including determination of freshness and identification of contaminants or adulteration. Applications of E-noses to a wide range of foods and beverages are considered, including: meat, fish, grains, alcoholic drinks, non-alcoholic drinks, fruits, milk and dairy products, olive oils, nuts, fresh vegetables and eggs. PMID- 22319333 TI - BARI+: a biometric based distributed key management approach for wireless body area networks. AB - Wireless body area networks (WBAN) consist of resource constrained sensing devices just like other wireless sensor networks (WSN). However, they differ from WSN in topology, scale and security requirements. Due to these differences, key management schemes designed for WSN are inefficient and unnecessarily complex when applied to WBAN. Considering the key management issue, WBAN are also different from WPAN because WBAN can use random biometric measurements as keys. We highlight the differences between WSN and WBAN and propose an efficient key management scheme, which makes use of biometrics and is specifically designed for WBAN domain. PMID- 22319334 TI - A monitoring and advisory system for diabetes patient management using a rule based method and KNN. AB - Diabetes is difficult to control and it is important to manage the diabetic's blood sugar level and prevent the associated complications by appropriate diabetic treatment. This paper proposes a system that can provide appropriate management for diabetes patients, according to their blood sugar level. The system is designed to send the information about the blood sugar levels, blood pressure, food consumption, exercise, etc., of diabetes patients, and manage the treatment by recommending and monitoring food consumption, physical activity, insulin dosage, etc., so that the patient can better manage their condition. The system is based on rules and the K Nearest Neighbor (KNN) classifier algorithm, to obtain the optimum treatment recommendation. Also, a monitoring system for diabetes patients is implemented using Web Services and Personal Digital Assistant (PDA) programming. PMID- 22319335 TI - Greatly improved small inductance measurement using quartz crystal parasitic capacitance compensation. AB - Generally, quartz crystal inductance frequency pulling in oscillators is very low and therefore is not often used in practice. The new method of improving frequency pullability uses inductance to compensate for quartz stray capacitances. To this end, a special AT fundamental quartz crystal working near the antiresonance frequency is selected. By modifying its equivalent circuit with load inductance and series tuning capacitance, the magnetic sensing of the circuit can be highly improved. The experimental results show that the new approach using the quartz crystal stray capacitance compensation method increases the frequency pulling range (from ?2 kHz/MUH to ?600 kHz/MUH) by *300 depending on the type of oscillator, making possible the measurement of nano-magnetic changes. PMID- 22319336 TI - Spectral identification of lighting type and character. AB - We investigated the optimal spectral bands for the identification of lighting types and the estimation of four major indices used to measure the efficiency or character of lighting. To accomplish these objectives we collected high resolution emission spectra (350 to 2,500 nm) for forty-three different lamps, encompassing nine of the major types of lamps used worldwide. The narrow band emission spectra were used to simulate radiances in eight spectral bands including the human eye photoreceptor bands (photopic, scotopic, and "meltopic") plus five spectral bands in the visible and near-infrared modeled on bands flown on the Landsat Thematic Mapper (TM). The high-resolution continuous spectra are superior to the broad band combinations for the identification of lighting type and are the standard for calculation of Luminous Efficacy of Radiation (LER), Correlated Color Temperature (CCT) and Color Rendering Index (CRI). Given the high cost that would be associated with building and flying a hyperspectral sensor with detection limits low enough to observe nighttime lights we conclude that it would be more feasible to fly an instrument with a limited number of broad spectral bands in the visible to near infrared. The best set of broad spectral bands among those tested is blue, green, red and NIR bands modeled on the band set flown on the Landsat Thematic Mapper. This set provides low errors on the identification of lighting types and reasonable estimates of LER and CCT when compared to the other broad band set tested. None of the broad band sets tested could make reasonable estimates of Luminous Efficacy (LE) or CRI. The photopic band proved useful for the estimation of LER. However, the three photoreceptor bands performed poorly in the identification of lighting types when compared to the bands modeled on the Landsat Thematic Mapper. Our conclusion is that it is feasible to identify lighting type and make reasonable estimates of LER and CCT using four or more spectral bands with minimal spectral overlap spanning the 0.4 to 1.0 um region. PMID- 22319337 TI - Challenges in the assembly and handling of thin film capped MEMS devices. AB - This paper discusses the assembly challenges considering the design and manufacturability of a Wafer Level Thin Film Package in MEMS applications. The assembly processes are discussed. The loads associated with these processes are illustrated and evaluated. Numerical calculations are combined with experimental observations in order to estimate the assembly risks. Our results emphasize the need for concurrent design for assembly. PMID- 22319338 TI - In situ roughness measurements for the solar cell industry using an atomic force microscope. AB - Areal roughness parameters always need to be under control in the thin film solar cell industry because of their close relationship with the electrical efficiency of the cells. In this work, these parameters are evaluated for measurements carried out in a typical fabrication area for this industry. Measurements are made using a portable atomic force microscope on the CNC diamond cutting machine where an initial sample of transparent conductive oxide is cut into four pieces. The method is validated by making a comparison between the parameters obtained in this process and in the laboratory under optimal conditions. Areal roughness parameters and Fourier Spectral Analysis of the data show good compatibility and open the possibility to use this type of measurement instrument to perform in situ quality control. This procedure gives a sample for evaluation without destroying any of the transparent conductive oxide; in this way 100% of the production can be tested, so improving the measurement time and rate of production. PMID- 22319340 TI - Design and analysis of impedance pumps utilizing electromagnetic actuation. AB - This study designs and analyzes an impedance pump utilizing an electromagnetic actuator. The pump is designed to have three major components, namely a lower glass substrate patterned with a copper micro-coil, a microchannel, and an upper glass cover plate attached a magnetic PDMS diaphragm. When a current is passed through the micro-coil, an electromagnetic force is established between the coil and the magnetic diaphragm. The resulting deflection of the PDMS diaphragm creates an acoustic impedance mismatch within the microchannel, which results in a net flow. In performing the analysis, simulated models of the magnetic field, the diaphragm displacement and the flow rate are developed using Ansoft/Maxwell3D, ANSYS FEA and FLUENT 6.3 CFD software, respectively. Overall, the simulated results reveal that a net flow rate of 52.8 MUL/min can be obtained using a diaphragm displacement of 31.5 MUm induced by a micro-coil input current of 0.5 A. The impedance pump proposed in this study provides a valuable contribution to the ongoing development of Lab-on-Chips (LoCs) systems. PMID- 22319339 TI - Phototactic and chemotactic signal transduction by transmembrane receptors and transducers in microorganisms. AB - Microorganisms show attractant and repellent responses to survive in the various environments in which they live. Those phototaxic (to light) and chemotaxic (to chemicals) responses are regulated by membrane-embedded receptors and transducers. This article reviews the following: (1) the signal relay mechanisms by two photoreceptors, Sensory Rhodopsin I (SRI) and Sensory Rhodopsin II (SRII) and their transducers (HtrI and HtrII) responsible for phototaxis in microorganisms; and (2) the signal relay mechanism of a chemoreceptor/transducer protein, Tar, responsible for chemotaxis in E. coli. Based on results mainly obtained by our group together with other findings, the possible molecular mechanisms for phototaxis and chemotaxis are discussed. PMID- 22319341 TI - Fluorescence-based comparative binding studies of the supramolecular host properties of PAMAM dendrimers using anilinonaphthalene sulfonates: unusual host dependent fluorescence titration behavior. AB - This work describes the fluorescence enhancement of the anilinonaphthalene sulfonate probes 1,8-ANS, 2,6-ANS, and 2,6-TNS via complexation with PAMAM dendrimer hosts of Generation 4, 5 and 6. The use of this set of three very closely related probes allows for comparative binding studies, with specific pairs of probes differing only in shape (1,8-ANS and 2,6-ANS), or in the presence of a methyl substituent (2,6-TNS vs. 2,6-ANS). The fluorescence of all three probes was significantly enhanced upon binding with PAMAM dendrimers, however in all cases except one, a very unusual spike was consistently observed in the host fluorescence titration plots (fluorescence enhancement vs. host concentration) at low dendrimer concentration. This unprecedented fluorescence titration curve shape makes fitting the data to a simple model such as 1:1 or 2:1 host: guest complexation very difficult; thus only qualitative comparisons of the relative binding of the three guests could be made based on host titrations. In the case of G4 and G5 dendrimers, the order of binding strength was qualitatively determined to be 1,8-ANS<2,6-ANS indicating that the more streamlined 2,6 substituted probes are a better match for the dendrimer cavity shape than the bulkier 1,8-substituted probe. This order of binding strength was also indicated by double fluorometric titration experiments, involving both host and guest titrations. Further double fluorometric titration experiments on 2,6-ANS in G4 dendrimer revealed a host concentration-dependent change in the nature of the host: guest complexation, with multiple guests complexed per host molecule at very low host concentrations, but less than one guest per host at higher concentrations. PMID- 22319342 TI - Towards fully integrated wireless impedimetric sensors. AB - We report on the design and characterization of the building blocks of a single chip wireless chemical sensor fabricated with a commercial complementary metal oxide-silicon (CMOS) technology, which includes two types of transducers for impedimetric measurements (4-electrode array and two interdigitated electrodes), instrumentation circuits, and a metal coil and circuits for inductive power and data transfer. The electrodes have been formed with a polycrystalline silicon layer of the technology by a simple post-process that does not require additional deposition or lithography steps, but just etching steps. A linear response to both conductivity and permittivity of solutions has been obtained. Wireless communication of the sensor chip with a readout unit has been demonstrated. The design of the chip was prepared for individual block characterization and not for full system characterization. The integration of chemical transducers within monolithic wireless platforms will lead to smaller, cheaper, and more reliable chemical microsensors, and will open up the door to numerous new applications where liquid mediums that are enclosed in sealed receptacles have to be measured. PMID- 22319343 TI - One-dimensional oxide nanostructures as gas-sensing materials: review and issues. AB - In this article, we review gas sensor application of one-dimensional (1D) metal oxide nanostructures with major emphases on the types of device structure and issues for realizing practical sensors. One of the most important steps in fabricating 1D-nanostructure devices is manipulation and making electrical contacts of the nanostructures. Gas sensors based on individual 1D nanostructure, which were usually fabricated using electron-beam lithography, have been a platform technology for fundamental research. Recently, gas sensors with practical applicability were proposed, which were fabricated with an array of 1D nanostructures using scalable micro-fabrication tools. In the second part of the paper, some critical issues are pointed out including long-term stability, gas selectivity, and room-temperature operation of 1D-nanostructure-based metal-oxide gas sensors. PMID- 22319344 TI - Ultra-high-speed image signal accumulation sensor. AB - Averaging of accumulated data is a standard technique applied to processing data with low signal-to-noise ratios (SNR), such as image signals captured in ultra high-speed imaging. The authors propose an architecture layout of an ultra-high speed image sensor capable of on-chip signal accumulation. The very high frame rate is enabled by employing an image sensor structure with a multi-folded CCD in each pixel, which serves as an in situ image signal storage. The signal accumulation function is achieved by direct connection of the first and the last storage elements of the in situ storage CCD. It has been thought that the multi folding is achievable only by driving electrodes with complicated and impractical layouts. Simple configurations of the driving electrodes to overcome the difficulty are presented for two-phase and four-phase transfer CCD systems. The in situ storage image sensor with the signal accumulation function is named Image Signal Accumulation Sensor (ISAS). PMID- 22319345 TI - FPGA-based fused smart sensor for dynamic and vibration parameter extraction in industrial robot links. AB - Intelligent robotics demands the integration of smart sensors that allow the controller to efficiently measure physical quantities. Industrial manipulator robots require a constant monitoring of several parameters such as motion dynamics, inclination, and vibration. This work presents a novel smart sensor to estimate motion dynamics, inclination, and vibration parameters on industrial manipulator robot links based on two primary sensors: an encoder and a triaxial accelerometer. The proposed smart sensor implements a new methodology based on an oversampling technique, averaging decimation filters, FIR filters, finite differences and linear interpolation to estimate the interest parameters, which are computed online utilizing digital hardware signal processing based on field programmable gate arrays (FPGA). PMID- 22319346 TI - Design and simulation of a MEMS control moment gyroscope for the sub-kilogram spacecraft. AB - A novel design of a microelectromechanical systems (MEMS) control moment gyroscope (MCMG) was proposed in this paper in order to generate a torque output with a magnitude of 10(-6) N.m. The MCMG consists of two orthogonal angular vibration systems, i.e., the rotor and gimbal; the coupling between which is based on the Coriolis effect and will cause a torque output in the direction perpendicular to the two vibrations. The angular rotor vibration was excited by the in-plane electrostatic rotary comb actuators, while the angular gimbal vibration was driven by an out-of-plane electrostatic parallel plate actuator. A possible process flow to fabricate the structure was proposed and discussed step by step. Furthermore, an array configuration using four MCMGs as an effective element, in which the torque was generated with a phase difference of 90 degrees between every two MCMGs, was proposed to smooth the inherent fluctuation of the torque output for a vibrational MCMG. The parasitic torque was cancelled by two opposite MCMGs with a phase difference of 180 degrees. The designed MCMG was about 1.1 cm*1.1 cm*0.04 cm in size and 0.1 g in weight. The simulation results showed that the maximum torque output of a MCMG, the resonant frequency of which was approximately 1,000 Hz, was about 2.5*10(-8) N.m. The element with four MCMGs could generate a torque of 5*10(-8) N.m. The torque output could reach a magnitude of 10(-6) N.m when the frequency was improved from 1,000 Hz to 10,000 Hz. Using arrays of 4*4 effective elements on a 1 kg spacecraft with a standard form factor of 10 cm*10 cm*10 cm, a 10 degrees attitude change could be achieved in 26.96 s. PMID- 22319347 TI - Corrosion sensor for monitoring the service condition of chloride-contaminated cement mortar. AB - A corrosion sensor for monitoring the corrosion state of cover mortar was developed. The sensor was tested in cement mortar, with and without the addition of chloride to simulate the adverse effects of chloride-contaminated environmental conditions on concrete structures. In brief, a linear polarization resistance method combined with an embeddable reference electrode was utilized to measure the polarization resistance (Rp) using built-in sensor electrodes. Subsequently, electrochemical impedance spectroscopy in the frequency range of 1 kHz to 50 kHz was used to obtain the cement mortar resistance (Rs). The results show that the polarization resistance is related to the chloride content and Rs; ln (Rp) is linearly related to the Rs values in mortar without added chloride. The relationships observed between the Rp of the steel anodes and the resistance of the surrounding cement mortar measured by the corrosion sensor confirms that Rs can indicate the corrosion state of concrete structures. PMID- 22319348 TI - Non-linearity analysis of depth and angular indexes for optimal stereo SLAM. AB - In this article, we present a real-time 6DoF egomotion estimation system for indoor environments using a wide-angle stereo camera as the only sensor. The stereo camera is carried in hand by a person walking at normal walking speeds 3-5 km/h. We present the basis for a vision-based system that would assist the navigation of the visually impaired by either providing information about their current position and orientation or guiding them to their destination through different sensing modalities. Our sensor combines two different types of feature parametrization: inverse depth and 3D in order to provide orientation and depth information at the same time. Natural landmarks are extracted from the image and are stored as 3D or inverse depth points, depending on a depth threshold. This depth threshold is used for switching between both parametrizations and it is computed by means of a non-linearity analysis of the stereo sensor. Main steps of our system approach are presented as well as an analysis about the optimal way to calculate the depth threshold. At the moment each landmark is initialized, the normal of the patch surface is computed using the information of the stereo pair. In order to improve long-term tracking, a patch warping is done considering the normal vector information. Some experimental results under indoor environments and conclusions are presented. PMID- 22319349 TI - A refrigerated web camera for photogrammetric video measurement inside biomass boilers and combustion analysis. AB - This paper describes a prototype instrumentation system for photogrammetric measuring of bed and ash layers, as well as for flying particle detection and pursuit using a single device (CCD) web camera. The system was designed to obtain images of the combustion process in the interior of a domestic boiler. It includes a cooling system, needed because of the high temperatures in the combustion chamber of the boiler. The cooling system was designed using CFD simulations to ensure effectiveness. This method allows more complete and real time monitoring of the combustion process taking place inside a boiler. The information gained from this system may facilitate the optimisation of boiler processes. PMID- 22319350 TI - Preparation of mesoporous and/or macroporous SnO2-based powders and their gas sensing properties as thick film sensors. AB - Mesoporous and/or macroporous SnO(2)-based powders have been prepared and their gas-sensing properties as thick film sensors towards H(2) and NO(2) have been investigated. The mesopores and macropores of various SnO(2)-based powders were controlled by self-assembly of sodium bis(2-ethylhexyl)sulfosuccinate and polymethyl-methacrylate (PMMA) microspheres (ca. 800 nm in diameter), respectively. The introduction of mesopores and macropores into SnO(2)-based sensors increased their sensor resistance in air significantly. The additions of SiO(2) and Sb(2)O(5) into mesoporous and/or macroporous SnO(2) were found to improve the sensing properties of the sensors. The addition of SiO(2) into mesoporous and/or macroporous SnO(2) was found to increase the sensor resistance in air, whereas doping of Sb(2)O(5) into mesoporous and/or macroporous SnO(2) was found to markedly reduce the sensor resistance in air, and to increase the response to 1,000 ppm H(2) as well as 1 ppm NO(2) in air. Among all the sensors tested, meso-macroporous SnO(2) added with 1 wt% SiO(2) and 5 wt% Sb(2)O(5), which were prepared with the above two templates simultaneously, exhibited the largest H(2) and NO(2) responses. PMID- 22319351 TI - Energy-efficiency analysis of a distributed queuing medium access control protocol for biomedical wireless sensor networks in saturation conditions. AB - The aging population and the high quality of life expectations in our society lead to the need of more efficient and affordable healthcare solutions. For this reason, this paper aims for the optimization of Medium Access Control (MAC) protocols for biomedical wireless sensor networks or wireless Body Sensor Networks (BSNs). The hereby presented schemes always have in mind the efficient management of channel resources and the overall minimization of sensors' energy consumption in order to prolong sensors' battery life. The fact that the IEEE 802.15.4 MAC does not fully satisfy BSN requirements highlights the need for the design of new scalable MAC solutions, which guarantee low-power consumption to the maximum number of body sensors in high density areas (i.e., in saturation conditions). In order to emphasize IEEE 802.15.4 MAC limitations, this article presents a detailed overview of this de facto standard for Wireless Sensor Networks (WSNs), which serves as a link for the introduction and initial description of our here proposed Distributed Queuing (DQ) MAC protocol for BSN scenarios. Within this framework, an extensive DQ MAC energy-consumption analysis in saturation conditions is presented to be able to evaluate its performance in relation to IEEE 802.5.4 MAC in highly dense BSNs. The obtained results show that the proposed scheme outperforms IEEE 802.15.4 MAC in average energy consumption per information bit, thus providing a better overall performance that scales appropriately to BSNs under high traffic conditions. These benefits are obtained by eliminating back-off periods and collisions in data packet transmissions, while minimizing the control overhead. PMID- 22319352 TI - Active integrated filters for RF-photonic channelizers. AB - A theoretical study of RF-photonic channelizers using four architectures formed by active integrated filters with tunable gains is presented. The integrated filters are enabled by two- and four-port nano-photonic couplers (NPCs). Lossless and three individual manufacturing cases with high transmission, high reflection, and symmetric couplers are assumed in the work. NPCs behavior is dependent upon the phenomenon of frustrated total internal reflection. Experimentally, photonic channelizers are fabricated in one single semiconductor chip on multi-quantum well epitaxial InP wafers using conventional microelectronics processing techniques. A state space modeling approach is used to derive the transfer functions and analyze the stability of these filters. The ability of adapting using the gains is demonstrated. Our simulation results indicate that the characteristic bandpass and notch filter responses of each structure are the basis of channelizer architectures, and optical gain may be used to adjust filter parameters to obtain a desired frequency magnitude response, especially in the range of 1-5 GHz for the chip with a coupler separation of ~9 mm. Preliminarily, the measurement of spectral response shows enhancement of quality factor by using higher optical gains. The present compact active filters on an InP-based integrated photonic circuit hold the potential for a variety of channelizer applications. Compared to a pure RF channelizer, photonic channelizers may perform both channelization and down-conversion in an optical domain. PMID- 22319353 TI - Photo-EMF sensitivity of porous silicon thin layer-crystalline silicon heterojunction to ammonia adsorption. AB - A new method of using photo-electromotive force in detecting gas and controlling sensitivity is proposed. Photo-electromotive force on the heterojunction between porous silicon thin layer and crystalline silicon wafer depends on the concentration of ammonia in the measurement chamber. A porous silicon thin layer was formed by electrochemical etching on p-type silicon wafer. A gas and light transparent electrical contact was manufactured to this porous layer. Photo-EMF sensitivity corresponding to ammonia concentration in the range from 10 ppm to 1,000 ppm can be maximized by controlling the intensity of illumination light. PMID- 22319354 TI - Carbon paste electrodes made from different carbonaceous materials: application in the study of antioxidants. AB - This work describes the sensing properties of carbon paste electrodes (CPES) prepared from three different types of carbonaceous materials: graphite, carbon microspheres and carbon nanotubes. The electrochemical responses towards antioxidants including vanillic acid, catechol, gallic acid, L-ascorbic acid and L-glutathione have been analyzed and compared. It has been demonstrated that the electrodes based on carbon microspheres show the best performances in terms of kinetics and stability, whereas G-CPEs presented the smallest detection limit for all the antioxidants analyzed. An array of electrodes has been constructed using the three types of electrodes. As demonstrated by means of Principal Component Analysis, the system is able to discriminate among antioxidants as a function of their chemical structure and reactivity. PMID- 22319355 TI - A trust evaluation algorithm for wireless sensor networks based on node behaviors and D-S evidence theory. AB - For wireless sensor networks (WSNs), many factors, such as mutual interference of wireless links, battlefield applications and nodes exposed to the environment without good physical protection, result in the sensor nodes being more vulnerable to be attacked and compromised. In order to address this network security problem, a novel trust evaluation algorithm defined as NBBTE (Node Behavioral Strategies Banding Belief Theory of the Trust Evaluation Algorithm) is proposed, which integrates the approach of nodes behavioral strategies and modified evidence theory. According to the behaviors of sensor nodes, a variety of trust factors and coefficients related to the network application are established to obtain direct and indirect trust values through calculating weighted average of trust factors. Meanwhile, the fuzzy set method is applied to form the basic input vector of evidence. On this basis, the evidence difference is calculated between the indirect and direct trust values, which link the revised D-S evidence combination rule to finally synthesize integrated trust value of nodes. The simulation results show that NBBTE can effectively identify malicious nodes and reflects the characteristic of trust value that 'hard to acquire and easy to lose'. Furthermore, it is obvious that the proposed scheme has an outstanding advantage in terms of illustrating the real contribution of different nodes to trust evaluation. PMID- 22319356 TI - Preparation and electrochemical characterization of a carbon ceramic electrode modified with ferrocenecarboxylic acid. AB - The present paper describes the characterization of a carbon ceramic electrode modified with ferrocenecarboxylic acid (designated as CCE/Fc) by electrochemical techniques and its detection ability for dopamine. From cyclic voltammetric experiments, it was observed that the CCE/Fc presented a redox pair at E(pa) = 405 mV and E(pc) = 335 mV (DeltaE = 70 mV), related to the ferrocene/ferrocenium process. Studies showed a considerably increase in the redox currents at the same oxidation potential of ferrocene (E(pa) = 414 mV vs. Ag/AgCl) in the presence of dopamine (DA), differently from those observed when using only the unmodified CCE, in which the anodic peak increase was considerably lower. From SWV experiments, it was observed that the AA (ascorbic acid) oxidation at CCE/Fc occurred in a different potential than the DA oxidation (with a peak separation of approximately 200 mV). Moreover, CCE/Fc did not respond to different AA concentrations, indicating that it is possible to determine DA without the AA interference with this electrode. PMID- 22319357 TI - A simple fiber Bragg grating-based sensor network architecture with self protecting and monitoring functions. AB - A novel fiber Bragg grating (FBG)-based passive sensor architecture, which can be used to protect the fiber cut and monitor the multiple sensors simultaneously, is proposed and experimentally demonstrated. Here, we employ a wavelength-tunable erbium-doped fiber (EDF) laser scheme with 25 km cavity length acting as the detecting light source in central office (CO). Each FBG sensor, serving as a feedback element, is used in proposed sensor architecture. By tuning the tunable bandpass filter (TBF) placing inside cavity to match the corresponding Bragg wavelength of FBG over the amplification bandwidth, we can retrieve the related wavelength lasing for the FBG sensing and monitoring simultaneously. Moreover, the survivability and capacity of the passive FBG sensor architecture can be also enhanced. PMID- 22319358 TI - A study of IEEE 802.15.4 security framework for wireless body area networks. AB - A Wireless Body Area Network (WBAN) is a collection of low-power and lightweight wireless sensor nodes that are used to monitor the human body functions and the surrounding environment. It supports a number of innovative and interesting applications, including ubiquitous healthcare and Consumer Electronics (CE) applications. Since WBAN nodes are used to collect sensitive (life-critical) information and may operate in hostile environments, they require strict security mechanisms to prevent malicious interaction with the system. In this paper, we first highlight major security requirements and Denial of Service (DoS) attacks in WBAN at Physical, Medium Access Control (MAC), Network, and Transport layers. Then we discuss the IEEE 802.15.4 security framework and identify the security vulnerabilities and major attacks in the context of WBAN. Different types of attacks on the Contention Access Period (CAP) and Contention Free Period (CFP) parts of the superframe are analyzed and discussed. It is observed that a smart attacker can successfully corrupt an increasing number of GTS slots in the CFP period and can considerably affect the Quality of Service (QoS) in WBAN (since most of the data is carried in CFP period). As we increase the number of smart attackers the corrupted GTS slots are eventually increased, which prevents the legitimate nodes to utilize the bandwidth efficiently. This means that the direct adaptation of IEEE 802.15.4 security framework for WBAN is not totally secure for certain WBAN applications. New solutions are required to integrate high level security in WBAN. PMID- 22319359 TI - Path renewal method in filtering based wireless sensor networks. AB - In applications of wireless sensor networks, there are many security issues. Attackers can create false reports and transmit the reports to the networks. These false reports can lead not only false alarms, but also the depletion of limited energy resources. In order to filter out such false reports during the forwarding process, Ye et al. proposed the statistical en-route filtering (SEF). Several research efforts to enhance the efficiency of SEF have been made. Especially, the path selection method proposed by Sun et al. can improve the detection power of SEF by considering the information on the filtering keys of and distances of upstream paths. However, such selection mechanism could lead to favored paths in heavy traffic, which would result in unbalanced energy consumption. In this paper, we propose a path renewal method to provide load balancing for sensor networks in terms of energy consumption. In our method, a node renews its upstream path to save energy resources if the remaining energy of and the communication traffic of the node exceed some threshold values. We show the effectiveness of the proposed method in terms of balanced energy consumption and filtering power by providing simulation results. PMID- 22319360 TI - The averaging effect of odorant mixing as determined by air dilution sensory tests: a case study on reduced sulfur compounds. AB - To learn more about the effects of mixing different odorants, a series of air dilution sensory (ADS) tests were conducted using four reduced sulfur compounds [RSC: hydrogen sulfide (H(2)S), methanethiol (CH(3)SH), dimethylsulfide (DMS), and dimethyldisulfide (DMDS)] at varying concentration levels. The tests were initially conducted by analyzing samples containing single individual RSCs at a wide range of concentrations. The resulting data were then evaluated to define the empirical relationship for each RSC between the dilution-to-threshold (D/T) ratio and odor intensity (OI) scaling. Based on the relationships defined for each individual RSC, the D/T ratios were estimated for a synthetic mixture of four RSCs. The effect of mixing was then examined by assessing the relative contribution of each RSC to those estimates with the aid of the actually measured D/T values. This stepwise test confirmed that the odor intensity of the synthetic mixture is not governed by the common theoretical basis (e.g., rule of additivity, synergism, or a stronger component model) but is best represented by the averaged contribution of all RSC components. The overall results of this study thus suggest that the mixing phenomenon between odorants with similar chemical properties (like RSC family) can be characterized by the averaging effect of all participants. PMID- 22319361 TI - A novel method for in-situ monitoring of local voltage, temperature and humidity distributions in fuel cells using flexible multi-functional micro sensors. AB - In this investigation, micro voltage, temperature and humidity sensors were fabricated and integrated for the first time on a stainless steel foil using micro-electro-mechanical systems (MEMS). These flexible multi-functional micro sensors have the advantages of high temperature resistance, flexibility, smallness, high sensitivity and precision of location. They were embedded in a proton exchange membrane fuel cell (PEMFC) and used to simultaneously measure variations in the inner voltage, temperature and humidity. The accuracy and reproducibility of the calibrated results obtained using the proposed micro sensors is excellent. The experimental results indicate that, at high current density and 100%RH or 75%RH, the relative humidity midstream and downstream saturates due to severe flooding. The performance of the PEM fuel cell can be stabilized using home-made flexible multi-functional micro sensors by the in-situ monitoring of local voltage, temperature and humidity distributions within it. PMID- 22319362 TI - MEMS-based power generation techniques for implantable biosensing applications. AB - Implantable biosensing is attractive for both medical monitoring and diagnostic applications. It is possible to monitor phenomena such as physical loads on joints or implants, vital signs, or osseointegration in vivo and in real time. Microelectromechanical (MEMS)-based generation techniques can allow for the autonomous operation of implantable biosensors by generating electrical power to replace or supplement existing battery-based power systems. By supplementing existing battery-based power systems for implantable biosensors, the operational lifetime of the sensor is increased. In addition, the potential for a greater amount of available power allows additional components to be added to the biosensing module, such as computational and wireless and components, improving functionality and performance of the biosensor. Photovoltaic, thermovoltaic, micro fuel cell, electrostatic, electromagnetic, and piezoelectric based generation schemes are evaluated in this paper for applicability for implantable biosensing. MEMS-based generation techniques that harvest ambient energy, such as vibration, are much better suited for implantable biosensing applications than fuel-based approaches, producing up to milliwatts of electrical power. High power density MEMS-based approaches, such as piezoelectric and electromagnetic schemes, allow for supplemental and replacement power schemes for biosensing applications to improve device capabilities and performance. In addition, this may allow for the biosensor to be further miniaturized, reducing the need for relatively large batteries with respect to device size. This would cause the implanted biosensor to be less invasive, increasing the quality of care received by the patient. PMID- 22319363 TI - A Parkinson's disease measurement system using laser lines and a CMOS image sensor. AB - This paper presents a non-invasive, non-contact system for the measurement of the arterial dorsum manus vibration waveforms of Parkinson disease patients. The laser line method is applied to detect the dorsum manus vibration in rest and postural situations. The proposed measurement system mainly consists of a laser diode and a low cost complementary metal-oxide semiconductor (CMOS) image sensor. Laser line and centroid methods are combined with the Fast Fourier Transform (FFT) in this study. The shape and frequency and relative frequency of the dorsum manus vibration waveforms can be detected rapidly using our Parkinson's disease measurement system. A laser line near the wrist joint is used as the testing line. The experimental results show an obvious increase in the amplitude and frequency of dorsum manus variation in the measured region in patients suffering from Parkinson's disease, indicating the obvious effects of the disease. Both in postural and rest state measurements, as the patient disease age increases the vibration frequency increases. The measurement system is well suited for evaluating and pre-diagnosing early stage Parkinson's disease. PMID- 22319364 TI - Resonant photonic biosensors with polarization-based multiparametric discrimination in each channel. AB - In this paper, we describe guided-mode resonance biochemical sensor technology. We briefly discuss sensor fabrication and show measured binding dynamics for example biomaterials in use in our laboratories. We then turn our attention to a particularly powerful attribute of this technology not possessed by competing methods. This attribute is the facile generation of multiple resonance peaks at an identical physical location on the sensor surface. These peaks respond uniquely to the biomolecular event, thereby enriching the data set available for event quantification. The peaks result from individual, polarization-dependent resonant leaky modes that are the foundation of this technology. Thus, by modeling the binding event and fitting to a rigorous electromagnetic formalism, we can determine individual attributes of the biolayer and its surroundings and avoid a separate reference site for background monitoring. Examples provide dual polarization quantification of biotin binding to a silane-coated sensor as well as binding of the cancer biomarker protein calreticulin to its monoclonal IgG capture antibody. Finally, we present dual-polarization resonance response for poly (allylamine hydrochloride) binding to the sensor with corresponding results of backfitting to a simple model; this differentiates the contributions from biolayer adhesion and background changes. PMID- 22319365 TI - Estimating three-dimensional orientation of human body parts by inertial/magnetic sensing. AB - User-worn sensing units composed of inertial and magnetic sensors are becoming increasingly popular in various domains, including biomedical engineering, robotics, virtual reality, where they can also be applied for real-time tracking of the orientation of human body parts in the three-dimensional (3D) space. Although they are a promising choice as wearable sensors under many respects, the inertial and magnetic sensors currently in use offer measuring performance that are critical in order to achieve and maintain accurate 3D-orientation estimates, anytime and anywhere. This paper reviews the main sensor fusion and filtering techniques proposed for accurate inertial/magnetic orientation tracking of human body parts; it also gives useful recipes for their actual implementation. PMID- 22319366 TI - Advances in SXFA-coated SAW chemical sensors for organophosphorous compound detection. AB - A polymer-coated surface acoustic wave (SAW)-based chemical sensor for organophosphorous compound sensing at extremely low concentrations was developed, in which a dual-delay-line oscillator coated with fluoroalcoholpolysiloxane (SXFA) acted as the sensor element. Response mechanism analysis was performed on the SXFA-coated chemical sensor, resulting in the optimal design parameters. The shear modulus of the SXFA, which is the key parameter for theoretical simulation, was extracted experimentally. New designs were done on the SAW devices to decrease the insertion loss. Referring to the new phase modulation approach, superior short-term frequency stability (+/-2 Hz in seconds) was achieved from the SAW oscillator using the fabricated 300 MHz delay line as the feedback element. In the sensor experiment on dimethylmethylphosphonate (DMMP) detection, the fabricated SXFA-coated chemical sensor exhibited an excellent threshold detection limit up to 0.004 mg/m(3) (0.7 ppb) and good sensitivity (~485 Hz/mg/m(3) for a DMMP concentration of 2~14 mg/m(3)). PMID- 22319367 TI - An autonomous wearable system for predicting and detecting localised muscle fatigue. AB - Muscle fatigue is an established area of research and various types of muscle fatigue have been clinically investigated in order to fully understand the condition. This paper demonstrates a non-invasive technique used to automate the fatigue detection and prediction process. The system utilises the clinical aspects such as kinematics and surface electromyography (sEMG) of an athlete during isometric contractions. Various signal analysis methods are used illustrating their applicability in real-time settings. This demonstrated system can be used in sports scenarios to promote muscle growth/performance or prevent injury. To date, research on localised muscle fatigue focuses on the clinical side and lacks the implementation for detecting/predicting localised muscle fatigue using an autonomous system. Results show that automating the process of localised muscle fatigue detection/prediction is promising. The autonomous fatigue system was tested on five individuals showing 90.37% accuracy on average of correct classification and an error of 4.35% in predicting the time to when fatigue will onset. PMID- 22319368 TI - Long period gratings in random hole optical fibers for refractive index sensing. AB - We have demonstrated the fabrication of long period gratings in random hole optical fibers. The long period gratings are fabricated by a point-by-point technique using a CO(2) laser. The gratings with a periodicity of 450 MUm are fabricated and a maximum coupling efficiency of -9.81 dB has been achieved. Sensing of different refractive indices in the surrounding mediums is demonstrated by applying standard liquids with refractive indices from 1.400 to 1.440 to the long period grating. PMID- 22319369 TI - Overview of the characteristics of micro- and nano-structured surface plasmon resonance sensors. AB - The performance of bio-chemical sensing devices has been greatly improved by the development of surface plasmon resonance (SPR) based sensors. Advancements in micro- and nano-fabrication technologies have led to a variety of structures in SPR sensing systems being proposed. In this review, SPR sensors (from typical Kretschmann prism configurations to fiber sensor schemes) with micro- or nano structures for local light field enhancement, extraordinary optical transmission, interference of surface plasmon waves, plasmonic cavities, etc. are discussed. We summarize and compare their performances and present guidelines for the design of SPR sensors. PMID- 22319370 TI - Sensor and display human factors based design constraints for head mounted and tele-operation systems. AB - For mobile imaging systems in head mounted displays and tele-operation systems it is important to maximize the amount of visual information transmitted to the human visual system without exceeding its input capacity. This paper aims to describe the design constraints on the imager and display systems of head mounted devices and tele-operated systems based upon the capabilities of the human visual system. We also present the experimental results of methods to improve the amount of visual information conveyed to a user when trying to display a high dynamic range image on a low dynamic range display. PMID- 22319371 TI - Secure chaotic map based block cryptosystem with application to camera sensor networks. AB - Recently, Wang et al. presented an efficient logistic map based block encryption system. The encryption system employs feedback ciphertext to achieve plaintext dependence of sub-keys. Unfortunately, we discovered that their scheme is unable to withstand key stream attack. To improve its security, this paper proposes a novel chaotic map based block cryptosystem. At the same time, a secure architecture for camera sensor network is constructed. The network comprises a set of inexpensive camera sensors to capture the images, a sink node equipped with sufficient computation and storage capabilities and a data processing server. The transmission security between the sink node and the server is gained by utilizing the improved cipher. Both theoretical analysis and simulation results indicate that the improved algorithm can overcome the flaws and maintain all the merits of the original cryptosystem. In addition, computational costs and efficiency of the proposed scheme are encouraging for the practical implementation in the real environment as well as camera sensor network. PMID- 22319372 TI - PCF-based cavity enhanced spectroscopic sensors for simultaneous multicomponent trace gas analysis. AB - A multiwavelength, multicomponent CRDS gas sensor operating on the basis of a compact photonic crystal fibre supercontinuum light source has been constructed. It features a simple design encompassing one radiation source, one cavity and one detection unit (a spectrograph with a fitted ICCD camera) that are common for all wavelengths. Multicomponent detection capability of the device is demonstrated by simultaneous measurements of the absorption spectra of molecular oxygen (spin forbidden b-X branch) and water vapor (polyads 4v, 4v + delta) in ambient atmospheric air. Issues related to multimodal cavity excitation, as well as to obtaining the best signal-to-noise ratio are discussed together with methods for their practical resolution based on operating the cavity in a "quasi continuum" mode and setting long camera gate widths, respectively. A comprehensive review of multiwavelength CRDS techniques is also given. PMID- 22319373 TI - Mobile location with NLOS identification and mitigation based on modified Kalman filtering. AB - In order to enhance accuracy and reliability of wireless location in the mixed line-of-sight (LOS) and non-line-of-sight (NLOS) environments, a robust mobile location algorithm is presented to track the position of a mobile node (MN). An extended Kalman filter (EKF) modified in the updating phase is utilized to reduce the NLOS error in rough wireless environments, in which the NLOS bias contained in each measurement range is estimated directly by the constrained optimization method. To identify the change of channel situation between NLOS and LOS, a low complexity identification method based on innovation vectors is proposed. Numerical results illustrate that the location errors of the proposed algorithm are all significantly smaller than those of the iterated NLOS EKF algorithm and the conventional EKF algorithm in different LOS/NLOS conditions. Moreover, this location method does not require any statistical distribution knowledge of the NLOS error. In addition, complexity experiments suggest that this algorithm supports real-time applications. PMID- 22319374 TI - The properties of terrestrial laser system intensity for measuring leaf geometries: a case study with Conference Pear trees (Pyrus communis). AB - Light Detection and Ranging (LiDAR) technology can be a valuable tool for describing and quantifying vegetation structure. However, because of their size, extraction of leaf geometries remains complicated. In this study, the intensity data produced by the Terrestrial Laser System (TLS) FARO LS880 is corrected for the distance effect and its relationship with the angle of incidence between the laser beam and the surface of the leaf of a Conference Pear tree (Pyrus commmunis) is established. The results demonstrate that with only intensity, this relationship has a potential for determining the angle of incidence with the leaves surface with a precision of +/-5 degrees for an angle of incidence smaller than 60 degrees , whereas it is more variable for an angle of incidence larger than 60 degrees . It appears that TLS beam footprint, leaf curvatures and leaf wrinkles have an impact on the relationship between intensity and angle of incidence, though, this analysis shows that the intensity of scanned leaves has a potential to eliminate ghost points and to improve their meshing. PMID- 22319375 TI - IJA: an efficient algorithm for query processing in sensor networks. AB - One of main features in sensor networks is the function that processes real time state information after gathering needed data from many domains. The component technologies consisting of each node called a sensor node that are including physical sensors, processors, actuators and power have advanced significantly over the last decade. Thanks to the advanced technology, over time sensor networks have been adopted in an all-round industry sensing physical phenomenon. However, sensor nodes in sensor networks are considerably constrained because with their energy and memory resources they have a very limited ability to process any information compared to conventional computer systems. Thus query processing over the nodes should be constrained because of their limitations. Due to the problems, the join operations in sensor networks are typically processed in a distributed manner over a set of nodes and have been studied. By way of example while simple queries, such as select and aggregate queries, in sensor networks have been addressed in the literature, the processing of join queries in sensor networks remains to be investigated. Therefore, in this paper, we propose and describe an Incremental Join Algorithm (IJA) in Sensor Networks to reduce the overhead caused by moving a join pair to the final join node or to minimize the communication cost that is the main consumer of the battery when processing the distributed queries in sensor networks environments. At the same time, the simulation result shows that the proposed IJA algorithm significantly reduces the number of bytes to be moved to join nodes compared to the popular synopsis join algorithm. PMID- 22319376 TI - The effect of tensile hysteresis and contact resistance on the performance of strain-resistant elastic-conductive webbing. AB - To use e-textiles as a strain-resistance sensor they need to be both elastic and conductive. Three kinds of elastic-conductive webbings, including flat, tubular, and belt webbings, made of Lycra fiber and carbon coated polyamide fiber, were used in this study. The strain-resistance properties of the webbings were evaluated in stretch-recovery tests and measured within 30% strain. It was found that tensile hysteresis and contact resistance significantly influence the tensile elasticity and the resistance sensitivity of the webbings. The results showed that the webbing structure definitely contributes to the tensile hysteresis and contact resistance. The smaller the friction is among the yarns in the belt webbing, the smaller the tensile hysteresis loss. However the close proximity of the conductive yarns in flat and tubular webbings results in a lower contact resistance. PMID- 22319377 TI - Design and implementation of a wireless sensor network-based remote water-level monitoring system. AB - The proposed remote water-level monitoring system (RWMS) consists of a field sensor module, a base station module, a data center module and a WEB releasing module. It has advantages in real time and synchronized remote control, expandability, and anti-jamming capabilities. The RWMS can realize real-time remote monitoring, providing early warning of events and protection of the safety of monitoring personnel under certain dangerous circumstances. This system has been successfully applied in Poyanghu Lake. The cost of the whole system is approximately 1,500 yuan (RMB). PMID- 22319378 TI - Leg motion classification with artificial neural networks using wavelet-based features of gyroscope signals. AB - We extract the informative features of gyroscope signals using the discrete wavelet transform (DWT) decomposition and provide them as input to multi-layer feed-forward artificial neural networks (ANNs) for leg motion classification. Since the DWT is based on correlating the analyzed signal with a prototype wavelet function, selection of the wavelet type can influence the performance of wavelet-based applications significantly. We also investigate the effect of selecting different wavelet families on classification accuracy and ANN complexity and provide a comparison between them. The maximum classification accuracy of 97.7% is achieved with the Daubechies wavelet of order 16 and the reverse bi-orthogonal (RBO) wavelet of order 3.1, both with similar ANN complexity. However, the RBO 3.1 wavelet is preferable because of its lower computational complexity in the DWT decomposition and reconstruction. PMID- 22319379 TI - Sensing phosphatidylserine in cellular membranes. AB - Phosphatidylserine, a phospholipid with a negatively charged head-group, is an important constituent of eukaryotic cellular membranes. On the plasma membrane, rather than being evenly distributed, phosphatidylserine is found preferentially in the inner leaflet. Disruption of this asymmetry, leading to the appearance of phosphatidylserine on the surface of the cell, is known to play a central role in both apoptosis and blood clotting. Despite its importance, comparatively little is known about phosphatidylserine in cells: its precise subcellular localization, transmembrane topology and intracellular dynamics are poorly characterized. The recent development of new, genetically-encoded probes able to detect phosphatidylserine within live cells, however, is leading to a more in-depth understanding of the biology of this phospholipid. This review aims to give an overview of the current methods for phosphatidylserine detection within cells, and some of the recent realizations derived from their use. PMID- 22319380 TI - A stereovision matching strategy for images captured with fish-eye lenses in forest environments. AB - We present a novel strategy for computing disparity maps from hemispherical stereo images obtained with fish-eye lenses in forest environments. At a first segmentation stage, the method identifies textures of interest to be either matched or discarded. This is achieved by applying a pattern recognition strategy based on the combination of two classifiers: Fuzzy Clustering and Bayesian. At a second stage, a stereovision matching process is performed based on the application of four stereovision matching constraints: epipolar, similarity, uniqueness and smoothness. The epipolar constraint guides the process. The similarity and uniqueness are mapped through a decision making strategy based on a weighted fuzzy similarity approach, obtaining a disparity map. This map is later filtered through the Hopfield Neural Network framework by considering the smoothness constraint. The combination of the segmentation and stereovision matching approaches makes the main contribution. The method is compared against the usage of simple features and combined similarity matching strategies. PMID- 22319381 TI - Measurement of blood pressure using an arterial pulsimeter equipped with a Hall device. AB - To measure precise blood pressure (BP) and pulse rate without using a cuff, we have developed an arterial pulsimeter consisting of a small, portable apparatus incorporating a Hall device. Regression analysis of the pulse wave measured during testing of the arterial pulsimeter was conducted using two equations of the BP algorithm. The estimated values of BP obtained by the cuffless arterial pulsimeter over 5 s were compared with values obtained using electronic or liquid mercury BP meters. The standard deviation between the estimated values and the measured values for systolic and diastolic BP were 8.3 and 4.9, respectively, which are close to the range of values of the BP International Standard. Detailed analysis of the pulse wave measured by the cuffless radial artery pulsimeter by detecting changes in the magnetic field can be used to develop a new diagnostic algorithm for BP, which can be applied to new medical apparatus such as the radial artery pulsimeter. PMID- 22319382 TI - Land use dynamics of the fast-growing Shanghai Metropolis, China (1979-2008) and its implications for land use and urban planning policy. AB - Through the integrated approach of remote sensing and geographic information system (GIS) techniques, four Landsat TM/ETM+ imagery acquired during 1979 and 2008 were used to quantitatively characterize the patterns of land use and land cover change (LULC) and urban sprawl in the fast-growing Shanghai Metropolis, China. Results showed that, the urban/built-up area grew on average by 4,242.06 ha yr(-1). Bare land grew by 1,594.66 ha yr(-1) on average. In contrast, cropland decreased by 3,286.26 ha yr(-1) on average, followed by forest and shrub, water, and tidal land, which decreased by 1,331.33 ha yr(-1), 903.43 ha yr(-1), and 315.72 ha yr(-1) on average, respectively. As a result, during 1979 and 2008 approximately 83.83% of the newly urban/built-up land was converted from cropland (67.35%), forest and shrub (9.12%), water (4.80%), and tidal land (2.19%). Another significant change was the continuous increase in regular residents, which played a very important role in contributing to local population growth and increase in urban/built-up land. This can be explained with this city's huge demand for investment and qualified labor since the latest industrial transformation. Moreover, with a decrease in cropland, the proportion of population engaged in farming decreased 13.84%. Therefore, significant socio economic transformation occurred, and this would lead to new demand for land resources. However, due to very scarce land resources and overload of population in Shanghai, the drive to achieve economic goals at the loss of cropland, water, and the other lands is not sustainable. Future urban planning policy aiming at ensuring a win-win balance between sustainable land use and economic growth is urgently needed. PMID- 22319383 TI - Optically defined modal sensors incorporating spiropyran-doped liquid crystals with piezoelectric sensors. AB - We integrated a piezoelectric sensing layer lamina containing liquid crystals (LC) and spiropyran (SP) in a LC/SP mixture to create an optically reconfigurable modal sensor for a cantilever beam. The impedance of this LC/SP lamina was decreased by UV irradiation which constituted the underlying mechanism to modulate the voltage externally applied to the piezoelectric actuating layer. Illuminating a specific pattern onto the LC/SP lamina provided us with a way to spatially modulate the piezoelectric vibration signal. We showed that if an UV illuminated pattern matches the strain distribution of a specific mode, a piezoelectric modal sensor can be created. Since UV illumination can be changed in situ in real-time, our results confirm for the first time since the inception of smart sensors, that an optically tailored modal sensor can be created. Some potential applications of this type of sensor include energy harvesting devices, bio-chips, vibration sensing and actuating devices. PMID- 22319384 TI - High-performance piezoresistive MEMS strain sensor with low thermal sensitivity. AB - This paper presents the experimental evaluation of a new piezoresistive MEMS strain sensor. Geometric characteristics of the sensor silicon carrier have been employed to improve the sensor sensitivity. Surface features or trenches have been introduced in the vicinity of the sensing elements. These features create stress concentration regions (SCRs) and as a result, the strain/stress field was altered. The improved sensing sensitivity compensated for the signal loss. The feasibility of this methodology was proved in a previous work using Finite Element Analysis (FEA). This paper provides the experimental part of the previous study. The experiments covered a temperature range from -50 degrees C to +50 degrees C. The MEMS sensors are fabricated using five different doping concentrations. FEA is also utilized to investigate the effect of material properties and layer thickness of the bonding adhesive on the sensor response. The experimental findings are compared to the simulation results to guide selection of bonding adhesive and installation procedure. Finally, FEA was used to analyze the effect of rotational/alignment errors. PMID- 22319385 TI - An energy-efficient MAC protocol using dynamic queue management for delay tolerant mobile sensor networks. AB - Conventional MAC protocols for wireless sensor network perform poorly when faced with a delay-tolerant mobile network environment. Characterized by a highly dynamic and sparse topology, poor network connectivity as well as data delay tolerance, delay-tolerant mobile sensor networks exacerbate the severe power constraints and memory limitations of nodes. This paper proposes an energy efficient MAC protocol using dynamic queue management (EQ-MAC) for power saving and data queue management. Via data transfers initiated by the target sink and the use of a dynamic queue management strategy based on priority, EQ-MAC effectively avoids untargeted transfers, increases the chance of successful data transmission, and makes useful data reach the target terminal in a timely manner. Experimental results show that EQ-MAC has high energy efficiency in comparison with a conventional MAC protocol. It also achieves a 46% decrease in packet drop probability, 79% increase in system throughput, and 25% decrease in mean packet delay. PMID- 22319386 TI - Sensor proxy mobile IPv6 (SPMIPv6)--a novel scheme for mobility supported IP WSNs. AB - IP based Wireless Sensor Networks (IP-WSNs) are gaining importance for their broad range of applications in health-care, home automation, environmental monitoring, industrial control, vehicle telematics and agricultural monitoring. In all these applications, mobility in the sensor network with special attention to energy efficiency is a major issue to be addressed. Host-based mobility management protocols are not suitable for IP-WSNs because of their energy inefficiency, so network based mobility management protocols can be an alternative for the mobility supported IP-WSNs. In this paper we propose a network based mobility supported IP-WSN protocol called Sensor Proxy Mobile IPv6 (SPMIPv6). We present its architecture, message formats and also evaluate its performance considering signaling cost, mobility cost and energy consumption. Our analysis shows that with respect to the number of IP-WSN nodes, the proposed scheme reduces the signaling cost by 60% and 56%, as well as the mobility cost by 62% and 57%, compared to MIPv6 and PMIPv6, respectively. The simulation results also show that in terms of the number of hops, SPMIPv6 decreases the signaling cost by 56% and 53% as well as mobility cost by 60% and 67% as compared to MIPv6 and PMIPv6 respectively. It also indicates that proposed scheme reduces the level of energy consumption significantly. PMID- 22319387 TI - A target coverage scheduling scheme based on genetic algorithms in directional sensor networks. AB - As a promising tool for monitoring the physical world, directional sensor networks (DSNs) consisting of a large number of directional sensors are attracting increasing attention. As directional sensors in DSNs have limited battery power and restricted angles of sensing range, maximizing the network lifetime while monitoring all the targets in a given area remains a challenge. A major technique to conserve the energy of directional sensors is to use a node wake-up scheduling protocol by which some sensors remain active to provide sensing services, while the others are inactive to conserve their energy. In this paper, we first address a Maximum Set Covers for DSNs (MSCD) problem, which is known to be NP-complete, and present a greedy algorithm-based target coverage scheduling scheme that can solve this problem by heuristics. This scheme is used as a baseline for comparison. We then propose a target coverage scheduling scheme based on a genetic algorithm that can find the optimal cover sets to extend the network lifetime while monitoring all targets by the evolutionary global search technique. To verify and evaluate these schemes, we conducted simulations and showed that the schemes can contribute to extending the network lifetime. Simulation results indicated that the genetic algorithm-based scheduling scheme had better performance than the greedy algorithm-based scheme in terms of maximizing network lifetime. PMID- 22319388 TI - Detection of hydrofluoric acid by a SiO2 sol-gel coating fiber-optic probe based on reflection-based localized surface plasmon resonance. AB - A novel fiber-optic probe based on reflection-based localized surface plasmon resonance (LSPR) was developed to quantify the concentration of hydrofluoric acid (HF) in aqueous solutions. The LSPR sensor was constructed with a gold nanoparticle-modified PMMA fiber, integrated with a SiO(2) sol-gel coating. This fiber-sensor was utilized to assess the relationship between HF concentration and SiO(2) sol-gel layer etching reduction. The results demonstrated the LSPR sensor was capable of detecting HF-related erosion of hydrofluoric acid solutions of concentrations ranging from 1% to 5% using Relative RI Change Rates. The development of the LSPR sensor constitutes the basis of a detector with significant sensitivity for practical use in monitoring HF solution concentrations. PMID- 22319389 TI - Effect of TiO2 on the gas sensing features of TiO2/PANi nanocomposites. AB - A nanocomposite of titanium dioxide (TiO(2)) and polyaniline (PANi) was synthesized by in-situ chemical polymerization using aniline (ANi) monomer and TiCl(4) as precursors. SEM pictures show that the nanocomposite was created in the form of long PANi chains decorated with TiO(2) nanoparticles. FTIR, Raman and UV-Vis spectra reveal that the PANi component undergoes an electronic structure modification as a result of the TiO(2) and PANi interaction. The electrical resistor of the nanocomposite is highly sensitive to oxygen and NH(3) gas, accounting for the physical adsorption of these gases. A nanocomposite with around 55% TiO(2) shows an oxygen sensitivity of 600-700%, 20-25 times higher than that of neat PANi. The n-p contacts between TiO(2) nanoparticles and PANi matrix give rise to variety of shallow donors and acceptor levels in the PANi band gap which enhance the physical adsorption of gas molecules. PMID- 22319390 TI - Effect of neuromuscular electrical muscle stimulation on energy expenditure in healthy adults. AB - Weight loss/weight control is a major concern in prevention of cardiovascular disease and the realm of health promotion. The primary aim of this study was to investigate the effect of neuromuscular electrical stimulation (NMES) at different intensities on energy expenditure (oxygen and calories) in healthy adults. The secondary aim was to develop a generalized linear regression (GEE) model to predict the increase of energy expenditure facilitated by NMES and identify factors (NMES stimulation intensity level, age, body mass index, weight, body fat percentage, waist/hip ratio, and gender) associated with this NMES induced increase of energy expenditure. Forty sedentary healthy adults (18 males and 22 females) participated. NMES was given at the following stimulation intensities for 10 minutes each: sensory level (E1), motor threshold (E2), and maximal intensity comfortably tolerated (E3). Cardiopulmonary gas exchange was evaluated during rest, NMES, and recovery stage. The results revealed that NMES at E2 and E3 significantly increased energy expenditure and the energy expenditure at recovery stage was still significantly higher than baseline. The GEE model demonstrated that a linear dose-response relationship existed between the stimulation intensity and the increase of energy expenditure. No subject's demographic or anthropometric characteristics tested were significantly associated with the increase of energy expenditure. This study suggested NMES may be used to serve as an additional intervention for weight loss programs. Future studies to develop electrical stimulators or stimulation electrodes to maximize the comfort of NMES are recommended. PMID- 22319391 TI - Forest cover classification by optimal segmentation of high resolution satellite imagery. AB - This study investigated whether high-resolution satellite imagery is suitable for preparing a detailed digital forest cover map that discriminates forest cover at the tree species level. First, we tried to find an optimal process for segmenting the high-resolution images using a region-growing method with the scale, color and shape factors in Definiens((r)) Professional 5.0. The image was classified by a traditional, pixel-based, maximum likelihood classification approach using the spectral information of the pixels. The pixels in each segment were reclassified using a segment-based classification (SBC) with a majority rule. Segmentation with strongly weighted color was less sensitive to the scale parameter and led to optimal forest cover segmentation and classification. The pixel-based classification (PBC) suffered from the "salt-and-pepper effect" and performed poorly in the classification of forest cover types, whereas the SBC helped to attenuate the effect and notably improved the classification accuracy. As a whole, SBC proved to be more suitable for classifying and delineating forest cover using high-resolution satellite images. PMID- 22319392 TI - One-to-one embedding between honeycomb mesh and Petersen-Torus networks. AB - As wireless mobile telecommunication bases organize their structure using a honeycomb-mesh algorithm, there are many studies about parallel processing algorithms like the honeycomb mesh in Wireless Sensor Networks. This paper aims to study the Peterson-Torus graph algorithm in regard to the continuity with honeycomb-mesh algorithm in order to apply the algorithm to sensor networks. Once a new interconnection network is designed, parallel algorithms are developed with huge research costs to use such networks. If the old network is embedded in a newly designed network, a developed algorithm in the old network is reusable in a newly designed network. Petersen-Torus has been designed recently, and the honeycomb mesh has already been designed as a well-known interconnection network. In this paper, we propose a one-to-one embedding algorithm for the honeycomb mesh (HMn) in the Petersen-Torus PT(n,n), and prove that dilation of the algorithm is 5, congestion is 2, and expansion is 5/3. The proposed one-to-one embedding is applied so that processor throughput can be minimized when the honeycomb mesh algorithm runs in the Petersen-Torus. PMID- 22319393 TI - Optical microcavity: sensing down to single molecules and atoms. AB - This review article discusses fundamentals of dielectric, low-loss, optical micro resonator sensing, including figures of merit and a variety of microcavity designs, and future perspectives in microcavity-based optical sensing. Resonance frequency and quality (Q) factor are altered as a means of detecting a small system perturbation, resulting in realization of optical sensing of a small amount of sample materials, down to even single molecules. Sensitivity, Q factor, minimum detectable index change, noises (in sensor system components and microcavity system including environments), microcavity size, and mode volume are essential parameters to be considered for optical sensing applications. Whispering gallery mode, photonic crystal, and slot-type microcavities typically provide compact, high-quality optical resonance modes for optical sensing applications. Surface Bloch modes induced on photonic crystals are shown to be a promising candidate thanks to large field overlap with a sample and ultra-high-Q resonances. Quantum optics effects based on microcavity quantum electrodynamics (QED) would provide novel single-photo-level detection of even single atoms and molecules via detection of doublet vacuum Rabi splitting peaks in strong coupling. PMID- 22319394 TI - Compact on-chip temperature sensors based on dielectric-loaded plasmonic waveguide-ring resonators. AB - The application of a waveguide-ring resonator based on dielectric-loaded surface plasmon-polariton waveguides as a temperature sensor is demonstrated in this paper and the influence of temperature change to the transmission through the waveguide-ring resonator system is comprehensively analyzed. The results show that the roundtrip phase change in the ring resonator due to the temperature change is the major reason for the transmission variation. The performance of the temperature sensor is also discussed and it is shown that for a waveguide-ring resonator with the resonator radius around 5 MUm and waveguide-ring gap of 500 nm which gives a footprint around 140 MUm(2), the temperature sensitivity at the order of 10(-2) K can be achieved with the input power of 100 MUW within the measurement sensitivity limit of a practical optical detector. PMID- 22319395 TI - Fabrication of a microbial biosensor based on QD-MWNT supports by a one-step radiation reaction and detection of phenolic compounds in red wines. AB - An Acaligense sp.-immobilized biosensor was fabricated based on QD-MWNT composites as an electron transfer mediator and a microbe immobilization support by a one-step radiation reaction and used for sensing phenolic compounds in commercial red wines. First, a quantum dot-modified multi-wall carbon nanotube (QD-MWNT) composite was prepared in the presence of MWNT by a one-step radiation reaction in an aqueous solution at room temperature. The successful preparation of the QD-MWNT composite was confirmed by XPS, TEM, and elemental analysis. Second, the microbial biosensor was fabricated by immobilization of Acaligense sp. on the surface of the composite thin film of a glassy carbon (GC) electrode, which was prepared by a hand casting method with a mixture of the previously obtained composite and Nafion solution. The sensing ranges of the microbial biosensor based on CdS-MWNT and Cu(2)S-MWNT supports were 0.5-5.0 mM and 0.7-10 mM for phenol in a phosphate buffer solution, respectively. Total concentration of phenolic compounds contained in commercial red wines was also determined using the prepared microbial immobilized biosensor. PMID- 22319396 TI - Energy saving effects of wireless sensor networks: a case study of convenience stores in Taiwan. AB - Wireless sensor network (WSN) technology has been successfully applied to energy saving applications in many places, and plays a significant role in achieving power conservation. However, previous studies do not discuss WSN costs and cost recovery. The application of WSNs is currently limited to research and laboratory experiments, and not mass industrial production, largely because business owners are unfamiliar with the possible favorable return and cost-recovery on WSN investments. Therefore, this paper focuses on the cost-recovery of WSNs and how to reduce air conditioning energy consumption in convenience stores. The WSN used in this study provides feedback to the gateway and adopts the predicted mean vote (PMV) and computational fluid dynamics (CFD) methods to allow customers to shop in a comfortable yet energy-saving environment. Four convenience stores in Taipei have used the proposed WSN since 2008. In 2008, the experiment was initially designed to optimize air-conditioning for energy saving, but additions to the set up continued beyond 2008, adding the thermal comfort and crowds peak, off-peak features in 2009 to achieve human-friendly energy savings. Comparison with 2007 data, under the same comfort conditions, shows that the power savings increased by 40% (2008) and 53% (2009), respectively. The cost of the WSN equipment was 500 US dollars. Experimental results, including three years of analysis and calculations, show that the marginal energy conservation benefit of the four convenience stores achieved energy savings of up to 53%, recovering all costs in approximately 5 months. The convenience store group participating in this study was satisfied with the efficiency of energy conservation because of the short cost-recovery period. PMID- 22319397 TI - Ultra wide-band localization and SLAM: a comparative study for mobile robot navigation. AB - In this work, a comparative study between an Ultra Wide-Band (UWB) localization system and a Simultaneous Localization and Mapping (SLAM) algorithm is presented. Due to its high bandwidth and short pulses length, UWB potentially allows great accuracy in range measurements based on Time of Arrival (TOA) estimation. SLAM algorithms recursively estimates the map of an environment and the pose (position and orientation) of a mobile robot within that environment. The comparative study presented here involves the performance analysis of implementing in parallel an UWB localization based system and a SLAM algorithm on a mobile robot navigating within an environment. Real time results as well as error analysis are also shown in this work. PMID- 22319398 TI - Design and implementation of a CMOS light pulse receiver cell array for spatial optical communications. AB - A CMOS light pulse receiver (LPR) cell for spatial optical communications is designed and evaluated by device simulations and a prototype chip implementation. The LPR cell consists of a pinned photodiode and four transistors. It works under sub-threshold region of a MOS transistor and the source terminal voltage which responds to the logarithm of the photo current are read out with a source follower circuit. For finding the position of the light spot on the focal plane, an image pixel array is embedded on the same plane of the LPR cell array. A prototype chip with 640 * 240 image pixels and 640 * 240 LPR cells is implemented with 0.18 MUm CMOS technology. A proposed model of the transient response of the LPR cell agrees with the result of the device simulations and measurements. Both imaging at 60 fps and optical communication at the carrier frequency of 1 MHz are successfully performed. The measured signal amplitude and the calculation results of photocurrents show that the spatial optical communication up to 100 m is feasible using a 10 * 10 LED array. PMID- 22319399 TI - Observing GLUT4 translocation in live L6 cells using quantum dots. AB - The glucose transporter 4 (GLUT4) plays a key role in maintaining whole body glucose homeostasis. Tracking GLUT4 in space and time can provide new insights for understanding the mechanisms of insulin-regulated GLUT4 translocation. Organic dyes and fluorescent proteins were used in previous studies for investigating the traffic of GLUT4 in skeletal muscle cells and adipocytes. Because of their relative weak fluorescent signal against strong cellular autofluorescence background and their fast photobleaching rate, most studies only focused on particular segments of GLUT4 traffic. In this study, we have developed a new method for observing the translocation of GLUT4 targeted with photostable and bright quantum dots (QDs) in live L6 cells. QDs were targeted to GLUT4myc specifically and internalized with GLUT4myc through receptor-mediated endocytosis. Compared with traditional fluorescence dyes and fluorescent proteins, QDs with high brightness and extremely photostability are suitable for long-term single particle tracking, so individual GLUT4-QD complex can be easily detected and tracked for long periods of time. This newly described method will be a powerful tool for observing the translocation of GLUT4 in live L6 cells. PMID- 22319400 TI - Fuzzy adaptive interacting multiple model nonlinear filter for integrated navigation sensor fusion. AB - In this paper, the application of the fuzzy interacting multiple model unscented Kalman filter (FUZZY-IMMUKF) approach to integrated navigation processing for the maneuvering vehicle is presented. The unscented Kalman filter (UKF) employs a set of sigma points through deterministic sampling, such that a linearization process is not necessary, and therefore the errors caused by linearization as in the traditional extended Kalman filter (EKF) can be avoided. The nonlinear filters naturally suffer, to some extent, the same problem as the EKF for which the uncertainty of the process noise and measurement noise will degrade the performance. As a structural adaptation (model switching) mechanism, the interacting multiple model (IMM), which describes a set of switching models, can be utilized for determining the adequate value of process noise covariance. The fuzzy logic adaptive system (FLAS) is employed to determine the lower and upper bounds of the system noise through the fuzzy inference system (FIS). The resulting sensor fusion strategy can efficiently deal with the nonlinear problem for the vehicle navigation. The proposed FUZZY-IMMUKF algorithm shows remarkable improvement in the navigation estimation accuracy as compared to the relatively conventional approaches such as the UKF and IMMUKF. PMID- 22319401 TI - Olfaction and hearing based mobile robot navigation for odor/sound source search. AB - Bionic technology provides a new elicitation for mobile robot navigation since it explores the way to imitate biological senses. In the present study, the challenging problem was how to fuse different biological senses and guide distributed robots to cooperate with each other for target searching. This paper integrates smell, hearing and touch to design an odor/sound tracking multi-robot system. The olfactory robot tracks the chemical odor plume step by step through information fusion from gas sensors and airflow sensors, while two hearing robots localize the sound source by time delay estimation (TDE) and the geometrical position of microphone array. Furthermore, this paper presents a heading direction based mobile robot navigation algorithm, by which the robot can automatically and stably adjust its velocity and direction according to the deviation between the current heading direction measured by magnetoresistive sensor and the expected heading direction acquired through the odor/sound localization strategies. Simultaneously, one robot can communicate with the other robots via a wireless sensor network (WSN). Experimental results show that the olfactory robot can pinpoint the odor source within the distance of 2 m, while two hearing robots can quickly localize and track the olfactory robot in 2 min. The devised multi-robot system can achieve target search with a considerable success ratio and high stability. PMID- 22319402 TI - Effects of calcination temperature and acid-base properties on mixed potential ammonia sensors modified by metal oxides. AB - Mixed potential sensors were fabriated using yttria-stabilized zirconia (YSZ) as a solid electrolyte and a mixture of Au and various metal oxides as a sensing electrode. The effects of calcination temperature ranging from 600 to 1,000 degrees C and acid-base properties of the metal oxides on the sensing properties were examined. The selective sensing of ammonia was achieved by modification of the sensing electrode using MoO(3), Bi(2)O(3) and V(2)O(5), while the use of WO(3,) Nb(2)O(5) and MgO was not effective. The melting points of the former group were below 820 degrees C, while those of the latter group were higher than 1,000 degrees C. Among the former group, the selective sensing of ammonia was strongly dependent on the calcination temperature, which was optimum around melting point of the corresponding metal oxides. The good spreading of the metal oxides on the electrode is suggested to be one of the important factors. In the former group, the relative response of ammonia to propene was in the order of MoO(3) > Bi(2)O(3) > V(2)O(5), which agreed well with the acidity of the metal oxides. The importance of the acidic properties of metal oxides for ammonia sensing was clarified. PMID- 22319403 TI - 3-D modeling of tomato canopies using a high-resolution portable scanning lidar for extracting structural information. AB - In the present study, an attempt was made to produce a precise 3D image of a tomato canopy using a portable high-resolution scanning lidar. The tomato canopy was scanned by the lidar from three positions surrounding it. Through the scanning, the point cloud data of the canopy were obtained and they were co registered. Then, points corresponding to leaves were extracted and converted into polygon images. From the polygon images, leaf areas were accurately estimated with a mean absolute percent error of 4.6%. Vertical profile of leaf area density (LAD) and leaf area index (LAI) could be also estimated by summing up each leaf area derived from the polygon images. Leaf inclination angle could be also estimated from the 3-D polygon image. It was shown that leaf inclination angles had different values at each part of a leaf. PMID- 22319405 TI - Ultrasonic and LIDAR sensors for electronic canopy characterization in vineyards: advances to improve pesticide application methods. AB - Canopy characterization is a key factor to improve pesticide application methods in tree crops and vineyards. Development of quick, easy and efficient methods to determine the fundamental parameters used to characterize canopy structure is thus an important need. In this research the use of ultrasonic and LIDAR sensors have been compared with the traditional manual and destructive canopy measurement procedure. For both methods the values of key parameters such as crop height, crop width, crop volume or leaf area have been compared. Obtained results indicate that an ultrasonic sensor is an appropriate tool to determine the average canopy characteristics, while a LIDAR sensor provides more accuracy and detailed information about the canopy. Good correlations have been obtained between crop volume (C(VU)) values measured with ultrasonic sensors and leaf area index, LAI (R(2) = 0.51). A good correlation has also been obtained between the canopy volume measured with ultrasonic and LIDAR sensors (R(2) = 0.52). Laser measurements of crop height (C(HL)) allow one to accurately predict the canopy volume. The proposed new technologies seems very appropriate as complementary tools to improve the efficiency of pesticide applications, although further improvements are still needed. PMID- 22319406 TI - Self-mixing thin-slice solid-state laser metrology. AB - This paper reviews the dynamic effect of thin-slice solid-state lasers subjected to frequency-shifted optical feedback, which led to the discovery of the self mixing modulation effect, and its applications to quantum-noise-limited versatile laser metrology systems with extreme optical sensitivity. PMID- 22319407 TI - Application of flexible micro temperature sensor in oxidative steam reforming by a methanol micro reformer. AB - Advances in fuel cell applications reflect the ability of reformers to produce hydrogen. This work presents a flexible micro temperature sensor that is fabricated based on micro-electro-mechanical systems (MEMS) technology and integrated into a flat micro methanol reformer to observe the conditions inside that reformer. The micro temperature sensor has higher accuracy and sensitivity than a conventionally adopted thermocouple. Despite various micro temperature sensor applications, integrated micro reformers are still relatively new. This work proposes a novel method for integrating micro methanol reformers and micro temperature sensors, subsequently increasing the methanol conversion rate and the hydrogen production rate by varying the fuel supply rate and the water/methanol ratio. Importantly, the proposed micro temperature sensor adequately controls the interior temperature during oxidative steam reforming of methanol (OSRM), with the relevant parameters optimized as well. PMID- 22319408 TI - Development of a stereo vision measurement system for a 3D three-axial pneumatic parallel mechanism robot arm. AB - In this paper, a stereo vision 3D position measurement system for a three-axial pneumatic parallel mechanism robot arm is presented. The stereo vision 3D position measurement system aims to measure the 3D trajectories of the end effector of the robot arm. To track the end-effector of the robot arm, the circle detection algorithm is used to detect the desired target and the SAD algorithm is used to track the moving target and to search the corresponding target location along the conjugate epipolar line in the stereo pair. After camera calibration, both intrinsic and extrinsic parameters of the stereo rig can be obtained, so images can be rectified according to the camera parameters. Thus, through the epipolar rectification, the stereo matching process is reduced to a horizontal search along the conjugate epipolar line. Finally, 3D trajectories of the end effector are computed by stereo triangulation. The experimental results show that the stereo vision 3D position measurement system proposed in this paper can successfully track and measure the fifth-order polynomial trajectory and sinusoidal trajectory of the end-effector of the three- axial pneumatic parallel mechanism robot arm. PMID- 22319409 TI - Comparison between Normalised and Unnormalised 454-Sequencing Libraries for Small Scale RNA-Seq Studies. AB - Next-generation sequencing of transcriptomes (RNA-Seq) is being used increasingly in studies of nonmodel organisms. Here, we evaluate the effectiveness of normalising cDNA libraries prior to sequencing in a small-scale study of the zebra finch. We find that assemblies produced from normalised libraries had a larger number of contigs but used fewer reads compared to unnormalised libraries. Considerably more genes were also detected using the contigs produced from normalised cDNA, and microsatellite discovery was up to 73% more efficient in these. There was a positive correlation between the detected expression level of genes in normalised and unnormalised cDNA, and there was no difference in the number of genes identified as being differentially expressed between blood and spleen for the normalised and unnormalised libraries. We conclude that normalised cDNA libraries are preferable for many applications of RNA-Seq and that these can also be used in quantitative gene expression studies. PMID- 22319410 TI - Predicting poor outcomes in heart failure. AB - BACKGROUND: Health plans must prioritize disease management efforts to reduce hospitalization and mortality rates in heart failure patients. METHODS AND RESULTS: We developed a risk model to predict the 5-year risk of mortality or hospitalization for heart failure among patients at a large health maintenance organization. We identified 4696 patients who had an echocardiogram and a heart failure diagnosis from 1999 to 2004.We observed a 56% five-year risk of hospitalization for heart failure or death (95% confidence interval, 54% to 58%). The hazard ratios for echocardiogram data contributed statistically significantly to the model, but echocardiogram findings did not improve our ability to predict risk accurately once we had accounted for demographic characteristics and clinical findings. A more complex model demonstrated a modest capacity to accurately predict risk. Our risk model discriminated the highest- and lowest risk patients with limited success-the observed risk was 3 times higher in the highest risk quintile, compared with the lowest-risk quintile. CONCLUSIONS: Using data available from electronic health records, we developed a series of risk prediction models for poor outcomes in patients with heart failure. We found that a relatively simple model is as effective as a more complex model, but that all the models predict with only modest accuracy. Until better prediction variables are available for heart failure patients, our prediction model may be valuable for prioritizing centralized disease management program efforts by stratifying patients according to their absolute risk of poor outcomes. PMID- 22319411 TI - Napa Immunization Study: Immunization Rates for Children with Publicly Funded Insurance Compared with those with Private Health Insurance in a Suburban Medical Office. AB - INTRODUCTION: Healthy People 2020 set a goal to increase the proportion of children who receive the recommended doses of Diphtheria Tetanus and Pertussis, polio, measles mumps and rubella, Haemophilus influenzae type b, hepatitis B, varicella and pneumococcal conjugate vaccines to 80% from the 2009 baseline rate of 69%. The purpose of this study is to compare the recommended immunization rates for low-income children insured through publicly funded health insurance (PFI) to the rates for children with private health insurance (PHI) in a suburban medical office. METHODS: The immunization rates and health access measures of 109 children ages 24 to 48 months who had PFI were compared with 300 children of the same age with PHI in the same medical practice. RESULTS: Overall immunization rates for the study population were very high and exceeded the Healthy People 2020 goals for full immunization. Children with PFI had lower rates of immunization and fluoride prescriptions; however the differences were only significant in the cohort of children age two years. By three years of age, the immunization rates and the fluoride prescription rates were similar. There were no significant differences in health outcomes for Spanish-speaking compared with English-speaking children. DISCUSSION: Barriers to successful immunization practices and strategies to overcome those barriers are discussed. CONCLUSION: The successful immunization practices and secondary outcomes in this study are a reflection of the integrated care model in this practice that facilitates comprehensive, coordinated, and accessible care for patients and allows physicians and support staff to practice culturally sensitive and compassionate care-the definition of a medical home. PMID- 22319412 TI - A Single-Blinded, Direct Observational Study of PGY-1 Interns and PGY-2 Residents in Evaluating their History-Taking and Physical-Examination Skills. AB - BACKGROUND: Internal Medicine residents and interns are often the first contact for newly admitted patients in a teaching hospital. The proper evaluation, diagnosis, and treatment may depend on this initial encounter. OBJECTIVES: To evaluate the history-taking and physical-examination skills of interns/residents on new admissions to the medical floors; to compare data from the patient encounter to the chart for evidence of accuracy; to measure the time spent on the initial encounter. METHODS: An independent medical observer used a yes/no checklist with 60 variables in a single-blinded observational study. Frequency tables were generated and results were based on descriptive statistics. RESULTS: In 7 categories specifically aimed at chart review for accuracy, discrepancies were found between what medical post-graduate year (PGY)-1 interns and PGY-2 residents (interns/residents) recorded in the patient's chart and the observed actions during the patient encounter. There were 25 encounters observed. In 64%, the time spent on history taking was <7 minutes. In 68%, the time spent for the physical examination was <5 minutes. In 72%, patients were notasked about family medical history. None ofthe observed interns/residents took their own measurements of the patient's blood pressure. No intern/resident asked about recent weight loss, weight gain, level of salt intake, despite patients with history of hypertension; nor did they perform any examinations of the eye fundi and accommodation, thyroid, carotids, or hearing. The majority of patients were asked about chest pain, cough, nausea, vomiting, chief complaint, and the onset of symptoms. CONCLUSIONS: This study documents the poor overall performance in the quality of history-taking and physical-examination skills on newly admitted patients. PMID- 22319413 TI - Early detection of colon cancer-the kaiser permanente northwest 30-year history: how do we measure success? Is it the test, the number of tests, the stage, or the percentage of screen-detected patients? AB - INTRODUCTION: Colorectal cancer (CRC) is the fourth most common malignancy in the Kaiser Permanente Northwest (KPNW) Region. The goals of CRC screening are early diagnosis of cancer in the preclinical state, down-staging of tumors, and increasing survival. This historical review summarizes the screening strategies since 1980 and their impact on early diagnosis, stage, and survival. During this period, the KPNW Tumor Registry documented the stage and survival, and screen detection status of patients. We have observed that the percentage of screen detected case measure has provided critical information that has contributed to the present success. CRC screening efforts by the end of 2010 had provided early diagnosis for one-third of patients. METHODS: KPNW membership has undergone more than 540,000 fecal blood tests, an estimated 130,000 flexible sigmoidoscopies (FS), and more than 100,000 colonoscopies. Since 1980 members older than age 50 years have increased from 48,627 to 137,617. This report represents a review of 5458 patients. Since 1980, 5 distinct periods of CRC screening have been compared. In 1980, the CRC screening practice was primarily office-based fecal occult blood testing (FOBT) and proctosigmoidoscopy. Data from the initial home based FOBT testing initiative (1985), transitioning to an FS program (1995), adoption of colonoscopy (2005), and subsequent reintroduction of FOBT testing (2006) allows examination of results by period. After ever-increasing promotion of endoscopy, the goal of screening shifted from "screen detection to prevention by polypectomy." RESULTS: By reexamining the outcomes of the CRC strategies from 1980-2005, the nature of the colonoscopy label of "gold standard" was questioned leading to a return to FOBT testing. Since then, the percentage of screen detected patients exceeded expectations with a 6-fold increase (5% to 33%) allowing KPNW to reach its highest level of early detection. DISCUSSION: By examining the KPNW experience, we have come to better understand the significance of effectiveness measures: number of tests, stage of disease, percentage of screen-detected cancers and their relationship to survival. We examined the measures used to assess success and conclude that the current metrics-the number of examinations and disease stage-do not accurately reflect the effectiveness of screening efforts. Early detection of CRC saves lives when a program tests the most at-risk people. Using a good test (FOBT/fecal immunochemical test) that is able to reach more people, rather than the "perfect test" that reaches fewer people, transforms an ineffective program into a successful one. A critical element was the transition of the individual testing to population screening. PMID- 22319414 TI - Centering parenting: pilot implementation of a group model for teaching family medicine residents well-child care. PMID- 22319415 TI - Regional expansion of minimally invasive surgery for hysterectomy: implementation and methodology in a large multispecialty group. AB - INTRODUCTION: Approximately 600,000 hysterectomies are performed in the US each year, making hysterectomy the second most common major operation performed in women. Several methods can be used to perform this procedure. In 2009, a Cochrane Review concluded "that vaginal hysterectomy should be performed in preference to abdominal hysterectomy, where possible. Where vaginal hysterectomy is not possible, a laparoscopic approach may avoid the need for an abdominal hysterectomy. Risks and benefits of different approaches may however be influenced by the surgeon's experience. More research is needed, particularly to examine the long-term effects of the different types of surgery."This article reviews the steps that a large multispecialty group used to teach non-open hysterectomy methods to improve the quality of care for their patients and to decrease the number of inpatient procedures and therefore costs. The percentages of each type of hysterectomy performed yearly between 2005 and 2010 were calculated, as well as the length of stay (LOS) for each method. METHODS: A structured educational intervention with both didactic and hands-on exercises was created and rolled out to 12 medical centers. All patients undergoing hysterectomy for benign conditions through the Southern California Permanente Medical Group (a large multispecialty group that provides medical care to Kaiser Permanente patients in Southern California) between 2005 and 2010 were included. This amounted to 26,055 hysterectomies for benign conditions being performed by more than 350 obstetrician/gynecologists (Ob/Gyns). RESULTS: More than 300 Ob/Gyns took the course across 12 medical centers. On the basis of hospital discharge data, the total number of hysterectomies, types of hysterectomies, and LOS for each type were identified for each year. Between 2005 and 2010, the rate of non-open hysterectomies has increased 120% (from 38% to 78%) and the average LOS has decreased 31%. PMID- 22319416 TI - Quality measurement and improvement in general surgery. AB - Increasing emphasis is being placed on health care quality measurement and improvement in the US. Within general surgery, several sophisticated quality measurement and outcomes systems have been developed. These include the National Surgical Quality Improvement Program, the use of selective referral and centers of excellence, the Surgical Care Improvement Project, and the World Health Organization Surgical Safety Checklist. This article reviews each of these quality-improvement initiatives, highlights their relative contributions, and discusses future directions of quality improvement within general surgery. PMID- 22319417 TI - New technology review process: the laparoscopic adjustable gastric band. AB - The Interregional New Technologies Committee (INTC) is one evaluation route for new medical technologies or technologies with expanded indications within Kaiser Permanente (KP). The primary focus of the INTC is to consider all available published evidence on a particular technology, surgical technique, or implantable device for a specific clinical indication and provide a recommendation on the sufficiency of the evidence for determining net medical benefit to Permanente Medical Group leaders and Kaiser Foundation Health Plan management throughout KP Regions. This iterative process provides an objective, evidence-based assessment to inform decision making by physicians and support the most appropriate care for KP members. This overview illustrates the INTC process and how it supports clinical decision making using implantation of laparoscopic adjustable gastric bands (LAGBs) as an example. In February 2011, the US Food and Drug Administration (FDA) approved lowering the acceptable body mass index for the Lap Band from 35 to 30 kg/m(2) for patients with at least one comorbid condition. It is difficult to find published studies on medical technologies that have been recently approved by the FDA. The manufacturer often submits clinical data to the FDA, but details are frequently not publicly available at the time of approval. The LAGB example demonstrates the complex issues addressed by the INTC, particularly when there is some evidence of short-term improvement in outcomes with a medical device but little if any confirmation of long-term safety or effectiveness. PMID- 22319418 TI - A case of an abdominal mass: follicular lymphoma. AB - Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin lymphoma. The disease usually affects older individuals, with the average age at diagnosis being 63.5 years. Only in 4% of cases is the disease diagnosed in individuals younger than age 40 years. The case presented in this report describes the diagnosis of FL in a 38-year-old woman and highlights the variability of this disease. Tumor grading, disease staging, and the Follicular Lymphoma International Prognostic Index score can be valuable aids in prognosis. Treatment consists of close observation or radiation therapy for early-stage disease, and rituximab with combination chemotherapy regimens for more advanced disease. Cure is rare. Treatment is predominately handled by oncologists, but these patients will likely first present to their primary care physicians. Symptoms can be subtle at times, so it is essential to be able to recognize them to provide the patient with timely treatment. PMID- 22319419 TI - Does my patient have asthma? PMID- 22319420 TI - Suppressed wound healing in a patient with rheumatoid arthritis taking leflunomide (arava). AB - Although patients with rheumatoid arthritis taking disease-modifying antirheumatic drugs (DMARDs) are monitored for various medication adverse events, DMARDs, and leflunomide in particular, have effects that are not observed clinically, specifically adverse effects on wound healing. PMID- 22319421 TI - ECG Diagnosis: Pulmonary Embolism. PMID- 22319422 TI - Dermatology image: erythema multiforme. PMID- 22319423 TI - Image diagnosis: ultrasound in right lower quadrant pain. PMID- 22319424 TI - Physician-assisted suicide and euthanasia: can you even imagine teaching medical students how to end their patients' lives? AB - The peer-reviewed literature includes numerous well-informed opinions on the topics of euthanasia and physician-assisted suicide. However, there is a paucity of commentary on the interface of these issues with medical education. This is surprising, given the universal assumption that in the event of the legalization of euthanasia, the individuals on whom society expects to confer the primary responsibility for carrying out these acts are members of the medical profession. Medical students and residents would inevitably and necessarily be implicated. It is my perspective that everyone in the profession, including those charged with educating future generations of physicians, has a critical interest in participating in this ongoing debate. I explore potential implications for medical education of a widespread sanctioning of physician-inflicted and physician-assisted death. My analysis, which uses a consequential-basis approach, leads me to conclude that euthanasia, when understood to include physician aid in hastening death, is incommensurate with humanism and the practice of medicine that considers healing as its overriding mandate. I ask readers to imagine the consequences of being required to teach students how to end their patients' lives and urge medical educators to remain cognizant of their responsibility in upholding long-entrenched and foundational professional values. PMID- 22319425 TI - Bridging physician-patient perspectives following an adverse medical outcome. PMID- 22319426 TI - Patient-centered research from electronic medical records. PMID- 22319427 TI - Humanity before Science: Narrative Medicine, Clinical Practice, and Medical Education. PMID- 22319428 TI - Human visual search does not maximize the post-saccadic probability of identifying targets. AB - Researchers have conjectured that eye movements during visual search are selected to minimize the number of saccades. The optimal Bayesian eye movement strategy minimizing saccades does not simply direct the eye to whichever location is judged most likely to contain the target but makes use of the entire retina as an information gathering device during each fixation. Here we show that human observers do not minimize the expected number of saccades in planning saccades in a simple visual search task composed of three tokens. In this task, the optimal eye movement strategy varied, depending on the spacing between tokens (in the first experiment) or the size of tokens (in the second experiment), and changed abruptly once the separation or size surpassed a critical value. None of our observers changed strategy as a function of separation or size. Human performance fell far short of ideal, both qualitatively and quantitatively. PMID- 22319429 TI - In silico experimentation of glioma microenvironment development and anti-tumor therapy. AB - Tumor cells do not develop in isolation, but co-evolve with stromal cells and tumor-associated immune cells in a tumor microenvironment mediated by an array of soluble factors, forming a complex intercellular signaling network. Herein, we report an unbiased, generic model to integrate prior biochemical data and the constructed brain tumor microenvironment in silico as characterized by an intercellular signaling network comprising 5 types of cells, 15 cytokines, and 69 signaling pathways. The results show that glioma develops through three distinct phases: pre-tumor, rapid expansion, and saturation. We designed a microglia depletion therapy and observed significant benefit for virtual patients treated at the early stages but strikingly no therapeutic efficacy at all when therapy was given at a slightly later stage. Cytokine combination therapy exhibits more focused and enhanced therapeutic response even when microglia depletion therapy already fails. It was further revealed that the optimal combination depends on the molecular profile of individual patients, suggesting the need for patient stratification and personalized treatment. These results, obtained solely by observing the in silico dynamics of the glioma microenvironment with no fitting to experimental/clinical data, reflect many characteristics of human glioma development and imply new venues for treating tumors via selective targeting of microenvironmental components. PMID- 22319430 TI - Positive evolutionary selection of an HD motif on Alzheimer precursor protein orthologues suggests a functional role. AB - HD amino acid duplex has been found in the active center of many different enzymes. The dyad plays remarkably different roles in their catalytic processes that usually involve metal coordination. An HD motif is positioned directly on the amyloid beta fragment (Abeta) and on the carboxy-terminal region of the extracellular domain (CAED) of the human amyloid precursor protein (APP) and a taxonomically well defined group of APP orthologues (APPOs). In human Abeta HD is part of a presumed, RGD-like integrin-binding motif RHD; however, neither RHD nor RXD demonstrates reasonable conservation in APPOs. The sequences of CAEDs and the position of the HD are not particularly conserved either, yet we show with a novel statistical method using evolutionary modeling that the presence of HD on CAEDs cannot be the result of neutral evolutionary forces (p<0.0001). The motif is positively selected along the evolutionary process in the majority of APPOs, despite the fact that HD motif is underrepresented in the proteomes of all species of the animal kingdom. Position migration can be explained by high probability occurrence of multiple copies of HD on intermediate sequences, from which only one is kept by selective evolutionary forces, in a similar way as in the case of the "transcription binding site turnover." CAED of all APP orthologues and homologues are predicted to bind metal ions including Amyloid like protein 1 (APLP1) and Amyloid-like protein 2 (APLP2). Our results suggest that HDs on the CAEDs are most probably key components of metal-binding domains, which facilitate and/or regulate inter- or intra-molecular interactions in a metal ion-dependent or metal ion concentration-dependent manner. The involvement of naturally occurring mutations of HD (Tottori (D7N) and English (H6R) mutations) in early onset Alzheimer's disease gives additional support to our finding that HD has an evolutionary preserved function on APPOs. PMID- 22319431 TI - Stochastic de-repression of Rhodopsins in single photoreceptors of the fly retina. AB - The photoreceptors of the Drosophila compound eye are a classical model for studying cell fate specification. Photoreceptors (PRs) are organized in bundles of eight cells with two major types - inner PRs involved in color vision and outer PRs involved in motion detection. In wild type flies, most PRs express a single type of Rhodopsin (Rh): inner PRs express either Rh3, Rh4, Rh5 or Rh6 and outer PRs express Rh1. In outer PRs, the K(50) homeodomain protein Dve is a key repressor that acts to ensure exclusive Rh expression. Loss of Dve results in de repression of Rhodopsins in outer PRs, and leads to a wide distribution of expression levels. To quantify these effects, we introduce an automated image analysis method to measure Rhodopsin levels at the single cell level in 3D confocal stacks. Our sensitive methodology reveals cell-specific differences in Rhodopsin distributions among the outer PRs, observed over a developmental time course. We show that Rhodopsin distributions are consistent with a two-state model of gene expression, in which cells can be in either high or basal states of Rhodopsin production. Our model identifies a significant role of post transcriptional regulation in establishing the two distinct states. The timescale for interconversion between basal and high states is shown to be on the order of days. Our results indicate that even in the absence of Dve, the Rhodopsin regulatory network can maintain highly stable states. We propose that the role of Dve in outer PRs is to buffer against rare fluctuations in this network. PMID- 22319432 TI - Early warning signals for critical transitions: a generalized modeling approach. AB - Critical transitions are sudden, often irreversible, changes that can occur in a large variety of complex systems; signals that warn of critical transitions are therefore highly desirable. We propose a new method for early warning signals that integrates multiple sources of information and data about the system through the framework of a generalized model. We demonstrate our proposed approach through several examples, including a previously published fisheries model. We regard our method as complementary to existing early warning signals, taking an approach of intermediate complexity between model-free approaches and fully parameterized simulations. One potential advantage of our approach is that, under appropriate conditions, it may reduce the amount of time series data required for a robust early warning signal. PMID- 22319433 TI - OptCom: a multi-level optimization framework for the metabolic modeling and analysis of microbial communities. AB - Microorganisms rarely live isolated in their natural environments but rather function in consolidated and socializing communities. Despite the growing availability of high-throughput sequencing and metagenomic data, we still know very little about the metabolic contributions of individual microbial players within an ecological niche and the extent and directionality of interactions among them. This calls for development of efficient modeling frameworks to shed light on less understood aspects of metabolism in microbial communities. Here, we introduce OptCom, a comprehensive flux balance analysis framework for microbial communities, which relies on a multi-level and multi-objective optimization formulation to properly describe trade-offs between individual vs. community level fitness criteria. In contrast to earlier approaches that rely on a single objective function, here, we consider species-level fitness criteria for the inner problems while relying on community-level objective maximization for the outer problem. OptCom is general enough to capture any type of interactions (positive, negative or combinations thereof) and is capable of accommodating any number of microbial species (or guilds) involved. We applied OptCom to quantify the syntrophic association in a well-characterized two-species microbial system, assess the level of sub-optimal growth in phototrophic microbial mats, and elucidate the extent and direction of inter-species metabolite and electron transfer in a model microbial community. We also used OptCom to examine addition of a new member to an existing community. Our study demonstrates the importance of trade-offs between species- and community-level fitness driving forces and lays the foundation for metabolic-driven analysis of various types of interactions in multi-species microbial systems using genome-scale metabolic models. PMID- 22319434 TI - Viral proteins acquired from a host converge to simplified domain architectures. AB - The infection cycle of viruses creates many opportunities for the exchange of genetic material with the host. Many viruses integrate their sequences into the genome of their host for replication. These processes may lead to the virus acquisition of host sequences. Such sequences are prone to accumulation of mutations and deletions. However, in rare instances, sequences acquired from a host become beneficial for the virus. We searched for unexpected sequence similarity among the 900,000 viral proteins and all proteins from cellular organisms. Here, we focus on viruses that infect metazoa. The high-conservation analysis yielded 187 instances of highly similar viral-host sequences. Only a small number of them represent viruses that hijacked host sequences. The low conservation sequence analysis utilizes the Pfam family collection. About 5% of the 12,000 statistical models archived in Pfam are composed of viral-metazoan proteins. In about half of Pfam families, we provide indirect support for the directionality from the host to the virus. The other families are either wrongly annotated or reflect an extensive sequence exchange between the viruses and their hosts. In about 75% of cross-taxa Pfam families, the viral proteins are significantly shorter than their metazoan counterparts. The tendency for shorter viral proteins relative to their related host proteins accounts for the acquisition of only a fragment of the host gene, the elimination of an internal domain and shortening of the linkers between domains. We conclude that, along viral evolution, the host-originated sequences accommodate simplified domain compositions. We postulate that the trimmed proteins act by interfering with the fundamental function of the host including intracellular signaling, post translational modification, protein-protein interaction networks and cellular trafficking. We compiled a collection of hijacked protein sequences. These sequences are attractive targets for manipulation of viral infection. PMID- 22319435 TI - Novel approach to meta-analysis of microarray datasets reveals muscle remodeling related drug targets and biomarkers in Duchenne muscular dystrophy. AB - Elucidation of new biomarkers and potential drug targets from high-throughput profiling data is a challenging task due to a limited number of available biological samples and questionable reproducibility of differential changes in cross-dataset comparisons. In this paper we propose a novel computational approach for drug and biomarkers discovery using comprehensive analysis of multiple expression profiling datasets.The new method relies on aggregation of individual profiling experiments combined with leave-one-dataset-out validation approach. Aggregated datasets were studied using Sub-Network Enrichment Analysis algorithm (SNEA) to find consistent statistically significant key regulators within the global literature-extracted expression regulation network. These regulators were linked to the consistent differentially expressed genes.We have applied our approach to several publicly available human muscle gene expression profiling datasets related to Duchenne muscular dystrophy (DMD). In order to detect both enhanced and repressed processes we considered up- and down-regulated genes separately. Applying the proposed approach to the regulators search we discovered the disturbance in the activity of several muscle-related transcription factors (e.g. MYOG and MYOD1), regulators of inflammation, regeneration, and fibrosis. Almost all SNEA-derived regulators of down-regulated genes (e.g. AMPK, TORC2, PPARGC1A) correspond to a single common pathway important for fast-to-slow twitch fiber type transition. We hypothesize that this process can affect the severity of DMD symptoms, making corresponding regulators and downstream genes valuable candidates for being potential drug targets and exploratory biomarkers. PMID- 22319436 TI - Developmental maturation of dynamic causal control signals in higher-order cognition: a neurocognitive network model. AB - Cognitive skills undergo protracted developmental changes resulting in proficiencies that are a hallmark of human cognition. One skill that develops over time is the ability to problem solve, which in turn relies on cognitive control and attention abilities. Here we use a novel multimodal neurocognitive network-based approach combining task-related fMRI, resting-state fMRI and diffusion tensor imaging (DTI) to investigate the maturation of control processes underlying problem solving skills in 7-9 year-old children. Our analysis focused on two key neurocognitive networks implicated in a wide range of cognitive tasks including control: the insula-cingulate salience network, anchored in anterior insula (AI), ventrolateral prefrontal cortex and anterior cingulate cortex, and the fronto-parietal central executive network, anchored in dorsolateral prefrontal cortex and posterior parietal cortex (PPC). We found that, by age 9, the AI node of the salience network is a major causal hub initiating control signals during problem solving. Critically, despite stronger AI activation, the strength of causal regulatory influences from AI to the PPC node of the central executive network was significantly weaker and contributed to lower levels of behavioral performance in children compared to adults. These results were validated using two different analytic methods for estimating causal interactions in fMRI data. In parallel, DTI-based tractography revealed weaker AI-PPC structural connectivity in children. Our findings point to a crucial role of AI connectivity, and its causal cross-network influences, in the maturation of dynamic top-down control signals underlying cognitive development. Overall, our study demonstrates how a unified neurocognitive network model when combined with multimodal imaging enhances our ability to generalize beyond individual task activated foci and provides a common framework for elucidating key features of brain and cognitive development. The quantitative approach developed is likely to be useful in investigating neurodevelopmental disorders, in which control processes are impaired, such as autism and ADHD. PMID- 22319437 TI - Integrating flux balance analysis into kinetic models to decipher the dynamic metabolism of Shewanella oneidensis MR-1. AB - Shewanella oneidensis MR-1 sequentially utilizes lactate and its waste products (pyruvate and acetate) during batch culture. To decipher MR-1 metabolism, we integrated genome-scale flux balance analysis (FBA) into a multiple-substrate Monod model to perform the dynamic flux balance analysis (dFBA). The dFBA employed a static optimization approach (SOA) by dividing the batch time into small intervals (i.e., ~400 mini-FBAs), then the Monod model provided time dependent inflow/outflow fluxes to constrain the mini-FBAs to profile the pseudo steady-state fluxes in each time interval. The mini-FBAs used a dual-objective function (a weighted combination of "maximizing growth rate" and "minimizing overall flux") to capture trade-offs between optimal growth and minimal enzyme usage. By fitting the experimental data, a bi-level optimization of dFBA revealed that the optimal weight in the dual-objective function was time-dependent: the objective function was constant in the early growth stage, while the functional weight of minimal enzyme usage increased significantly when lactate became scarce. The dFBA profiled biologically meaningful dynamic MR-1 metabolisms: 1. the oxidative TCA cycle fluxes increased initially and then decreased in the late growth stage; 2. fluxes in the pentose phosphate pathway and gluconeogenesis were stable in the exponential growth period; and 3. the glyoxylate shunt was up regulated when acetate became the main carbon source for MR-1 growth. PMID- 22319438 TI - The role of animal models for research on severe malaria. PMID- 22319439 TI - Selecting an invertebrate model host for the study of fungal pathogenesis. PMID- 22319440 TI - Discrete cyclic di-GMP-dependent control of bacterial predation versus axenic growth in Bdellovibrio bacteriovorus. AB - Bdellovibrio bacteriovorus is a Delta-proteobacterium that oscillates between free-living growth and predation on Gram-negative bacteria including important pathogens of man, animals and plants. After entering the prey periplasm, killing the prey and replicating inside the prey bdelloplast, several motile B. bacteriovorus progeny cells emerge. The B. bacteriovorus HD100 genome encodes numerous proteins predicted to be involved in signalling via the secondary messenger cyclic di-GMP (c-di-GMP), which is known to affect bacterial lifestyle choices. We investigated the role of c-di-GMP signalling in B. bacteriovorus, focussing on the five GGDEF domain proteins that are predicted to function as diguanylyl cyclases initiating c-di-GMP signalling cascades. Inactivation of individual GGDEF domain genes resulted in remarkably distinct phenotypes. Deletion of dgcB (Bd0742) resulted in a predation impaired, obligately axenic mutant, while deletion of dgcC (Bd1434) resulted in the opposite, obligately predatory mutant. Deletion of dgcA (Bd0367) abolished gliding motility, producing bacteria capable of predatory invasion but unable to leave the exhausted prey. Complementation was achieved with wild type dgc genes, but not with GGAAF versions. Deletion of cdgA (Bd3125) substantially slowed predation; this was restored by wild type complementation. Deletion of dgcD (Bd3766) had no observable phenotype. In vitro assays showed that DgcA, DgcB, and DgcC were diguanylyl cyclases. CdgA lacks enzymatic activity but functions as a c-di-GMP receptor apparently in the DgcB pathway. Activity of DgcD was not detected. Deletion of DgcA strongly decreased the extractable c-di-GMP content of axenic Bdellovibrio cells. We show that c-di-GMP signalling pathways are essential for both the free-living and predatory lifestyles of B. bacteriovorus and that obligately predatory dgcC- can be made lacking a propensity to survive without predation of bacterial pathogens and thus possibly useful in anti-pathogen applications. In contrast to many studies in other bacteria, Bdellovibrio shows specificity and lack of overlap in c-di-GMP signalling pathways. PMID- 22319441 TI - Viral cyclins mediate separate phases of infection by integrating functions of distinct mammalian cyclins. AB - Gammaherpesvirus cyclins have expanded biochemical features relative to mammalian cyclins, and promote infection and pathogenesis including acute lung infection, viral persistence, and reactivation from latency. To define the essential features of the viral cyclin, we generated a panel of knock-in viruses expressing various viral or mammalian cyclins from the murine gammaherpesvirus 68 cyclin locus. Viral cyclins of both gammaherpesvirus 68 and Kaposi's sarcoma-associated herpesvirus supported all cyclin-dependent stages of infection, indicating functional conservation. Although mammalian cyclins could not restore lung replication, they did promote viral persistence and reactivation. Strikingly, distinct and non-overlapping mammalian cyclins complemented persistence (cyclin A, E) or reactivation from latency (cyclin D3). Based on these data, unique biochemical features of viral cyclins (e.g. enhanced kinase activation) are not essential to mediate specific processes during infection. What is essential for, and unique to, the viral cyclins is the integration of the activities of several different mammalian cyclins, which allows viral cyclins to mediate multiple, discrete stages of infection. These studies also demonstrated that closely related stages of infection, that are cyclin-dependent, are in fact genetically distinct, and thus predict that cyclin requirements may be used to tailor potential therapies for virus-associated diseases. PMID- 22319442 TI - Enhancement of chemokine function as an immunomodulatory strategy employed by human herpesviruses. AB - Herpes simplex virus (HSV) types 1 and 2 are highly prevalent human neurotropic pathogens that cause a variety of diseases, including lethal encephalitis. The relationship between HSV and the host immune system is one of the main determinants of the infection outcome. Chemokines play relevant roles in antiviral response and immunopathology, but the modulation of chemokine function by HSV is not well understood. We have addressed the modulation of chemokine function mediated by HSV. By using surface plasmon resonance and crosslinking assays we show that secreted glycoprotein G (SgG) from both HSV-1 and HSV-2 binds chemokines with high affinity. Chemokine binding activity was also observed in the supernatant of HSV-2 infected cells and in the plasma membrane of cells infected with HSV-1 wild type but not with a gG deficient HSV-1 mutant. Cell binding and competition experiments indicate that the interaction takes place through the glycosaminoglycan-binding domain of the chemokine. The functional relevance of the interaction was determined both in vitro, by performing transwell assays, time-lapse microscopy, and signal transduction experiments; and in vivo, using the air pouch model of inflammation. Interestingly, and in contrast to what has been observed for previously described viral chemokine binding proteins, HSV SgGs do not inhibit chemokine function. On the contrary, HSV SgGs enhance chemotaxis both in vitro and in vivo through increasing directionality, potency and receptor signaling. This is the first report, to our knowledge, of a viral chemokine binding protein from a human pathogen that increases chemokine function and points towards a previously undescribed strategy of immune modulation mediated by viruses. PMID- 22319443 TI - Msb2 shedding protects Candida albicans against antimicrobial peptides. AB - Msb2 is a sensor protein in the plasma membrane of fungi. In the human fungal pathogen C. albicans Msb2 signals via the Cek1 MAP kinase pathway to maintain cell wall integrity and allow filamentous growth. Msb2 doubly epitope-tagged in its large extracellular and small cytoplasmic domain was efficiently cleaved during liquid and surface growth and the extracellular domain was almost quantitatively released into the growth medium. Msb2 cleavage was independent of proteases Sap9, Sap10 and Kex2. Secreted Msb2 was highly O-glycosylated by protein mannosyltransferases including Pmt1 resulting in an apparent molecular mass of >400 kDa. Deletion analyses revealed that the transmembrane region is required for Msb2 function, while the large N-terminal and the small cytoplasmic region function to downregulate Msb2 signaling or, respectively, allow its induction by tunicamycin. Purified extracellular Msb2 domain protected fungal and bacterial cells effectively from antimicrobial peptides (AMPs) histatin-5 and LL 37. AMP inactivation was not due to degradation but depended on the quantity and length of the Msb2 glycofragment. C. albicans msb2 mutants were supersensitive to LL-37 but not histatin-5, suggesting that secreted rather than cell-associated Msb2 determines AMP protection. Thus, in addition to its sensor function Msb2 has a second activity because shedding of its glycofragment generates AMP quorum resistance. PMID- 22319444 TI - Immune subversion and quorum-sensing shape the variation in infectious dose among bacterial pathogens. AB - Many studies have been devoted to understand the mechanisms used by pathogenic bacteria to exploit human hosts. These mechanisms are very diverse in the detail, but share commonalities whose quantification should enlighten the evolution of virulence from both a molecular and an ecological perspective. We mined the literature for experimental data on infectious dose of bacterial pathogens in humans (ID50) and also for traits with which ID50 might be associated. These compilations were checked and complemented with genome analyses. We observed that ID50 varies in a continuous way by over 10 orders of magnitude. Low ID50 values are very strongly associated with the capacity of the bacteria to kill professional phagocytes or to survive in the intracellular milieu of these cells. Inversely, high ID50 values are associated with motile and fast-growing bacteria that use quorum-sensing based regulation of virulence factors expression. Infectious dose is not associated with genome size and shows insignificant phylogenetic inertia, in line with frequent virulence shifts associated with the horizontal gene transfer of a small number of virulence factors. Contrary to previous proposals, infectious dose shows little dependence on contact-dependent secretion systems and on the natural route of exposure. When all variables are combined, immune subversion and quorum-sensing are sufficient to explain two thirds of the variance in infectious dose. Our results show the key role of immune subversion in effective human infection by small bacterial populations. They also suggest that cooperative processes might be important for successful infection by bacteria with high ID50. Our results suggest that trade-offs between selection for population growth-related traits and selection for the ability to subvert the immune system shape bacterial infectiousness. Understanding these trade-offs provides guidelines to study the evolution of virulence and in particular the micro-evolutionary paths of emerging pathogens. PMID- 22319445 TI - The CTLA-4 and PD-1/PD-L1 inhibitory pathways independently regulate host resistance to Plasmodium-induced acute immune pathology. AB - The balance between pro-inflammatory and regulatory immune responses in determining optimal T cell activation is vital for the successful resolution of microbial infections. This balance is maintained in part by the negative regulators of T cell activation, CTLA-4 and PD-1/PD-L, which dampen effector responses during chronic infections. However, their role in acute infections, such as malaria, remains less clear. In this study, we determined the contribution of CTLA-4 and PD-1/PD-L to the regulation of T cell responses during Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (ECM) in susceptible (C57BL/6) and resistant (BALB/c) mice. We found that the expression of CTLA-4 and PD-1 on T cells correlates with the extent of pro-inflammatory responses induced during PbA infection, being higher in C57BL/6 than in BALB/c mice. Thus, ECM develops despite high levels of expression of these inhibitory receptors. However, antibody-mediated blockade of either the CTLA-4 or PD-1/PD L1, but not the PD-1/PD-L2, pathways during PbA-infection in ECM-resistant BALB/c mice resulted in higher levels of T cell activation, enhanced IFN-gamma production, increased intravascular arrest of both parasitised erythrocytes and CD8(+) T cells to the brain, and augmented incidence of ECM. Thus, in ECM resistant BALB/c mice, CTLA-4 and PD-1/PD-L1 represent essential, independent and non-redundant pathways for maintaining T cell homeostasis during a virulent malaria infection. Moreover, neutralisation of IFN-gamma or depletion of CD8(+) T cells during PbA infection was shown to reverse the pathologic effects of regulatory pathway blockade, highlighting that the aetiology of ECM in the BALB/c mice is similar to that in C57BL/6 mice. In summary, our results underscore the differential and complex regulation that governs immune responses to malaria parasites. PMID- 22319446 TI - Genetic pathway in acquisition and loss of vancomycin resistance in a methicillin resistant Staphylococcus aureus (MRSA) strain of clonal type USA300. AB - An isolate of the methicillin-resistant Staphylococcus aureus (MRSA) clone USA300 with reduced susceptibility to vancomycin (SG-R) (i.e, vancomycin-intermediate S. aureus, VISA) and its susceptible "parental" strain (SG-S) were recovered from a patient at the end and at the beginning of an unsuccessful vancomycin therapy. The VISA phenotype was unstable in vitro generating a susceptible revertant strain (SG-rev). The availability of these 3 isogenic strains allowed us to explore genetic correlates of antibiotic resistance as it emerged in vivo. Compared to the susceptible isolate, both the VISA and revertant strains carried the same point mutations in yycH, vraG, yvqF and lspA genes and a substantial deletion within an intergenic region. The revertant strain carried a single additional frameshift mutation in vraS which is part of two component regulatory system VraSR. VISA isolate SG-R showed complex alterations in phenotype: decreased susceptibility to other antibiotics, slow autolysis, abnormal cell division and increased thickness of cell wall. There was also altered expression of 239 genes including down-regulation of major virulence determinants. All phenotypic properties and gene expression profile returned to parental levels in the revertant strain. Introduction of wild type yvqF on a multicopy plasmid into the VISA strain caused loss of resistance along with loss of all the associated phenotypic changes. Introduction of the wild type vraSR into the revertant strain caused recovery of VISA type resistance. The yvqF/vraSR operon seems to function as an on/off switch: mutation in yvqF in strain SG-R turns on the vraSR system, which leads to increase in vancomycin resistance and down-regulation of virulence determinants. Mutation in vraS in the revertant strain turns off this regulatory system accompanied by loss of resistance and normal expression of virulence genes. Down-regulation of virulence genes may provide VISA strains with a "stealth" strategy to evade detection by the host immune system. PMID- 22319447 TI - Absence of HIV-1 evolution in the gut-associated lymphoid tissue from patients on combination antiviral therapy initiated during primary infection. AB - Mucosal mononuclear (MMC) CCR5+CD4+ T cells of the gastrointestinal (GI) tract are selectively infected and depleted during acute HIV-1 infection. Despite early initiation of combination antiretroviral therapy (cART), gut-associated lymphoid tissue (GALT) CD4+ T cell depletion and activation persist in the majority of HIV 1 positive individuals studied. This may result from ongoing HIV-1 replication and T-cell activation despite effective cART. We hypothesized that ongoing viral replication in the GI tract during cART would result in measurable viral evolution, with divergent populations emerging over time. Subjects treated during early HIV-1 infection underwent phlebotomy and flexible sigmoidoscopy with biopsies prior to and 15-24 months post initiation of cART. At the 2(nd) biopsy, three GALT phenotypes were noted, characterized by high, intermediate and low levels of immune activation. A representative case from each phenotype was analyzed. Each subject had plasma HIV-1 RNA levels <50 copies/ml at 2(nd) GI biopsy and CD4+ T cell reconstitution in the peripheral blood. Single genome amplification of full-length HIV-1 envelope was performed for each subject pre- and post-initiation of cART in GALT and PBMC. A total of 280 confirmed single genome sequences (SGS) were analyzed for experimental cases. For each subject, maximum likelihood phylogenetic trees derived from molecular sequence data showed no evidence of evolved forms in the GALT over the study period. During treatment, HIV-1 envelope diversity in GALT-derived SGS did not increase and post-treatment GALT-derived SGS showed no substantial genetic divergence from pre-treatment sequences within transmitted groups. Similar results were obtained from PBMC derived SGS. Our results reveal that initiation of cART during acute/early HIV-1 infection can result in the interruption of measurable viral evolution in the GALT, suggesting the absence of de-novo rounds of HIV-1 replication in this compartment during suppressive cART. PMID- 22319448 TI - Phagosomal rupture by Mycobacterium tuberculosis results in toxicity and host cell death. AB - Survival within macrophages is a central feature of Mycobacterium tuberculosis pathogenesis. Despite significant advances in identifying new immunological parameters associated with mycobacterial disease, some basic questions on the intracellular fate of the causative agent of human tuberculosis in antigen presenting cells are still under debate. To get novel insights into this matter, we used a single-cell fluorescence resonance energy transfer (FRET)-based method to investigate the potential cytosolic access of M. tuberculosis and the resulting cellular consequences in an unbiased, quantitative way. Analysis of thousands of THP-1 macrophages infected with selected wild-type or mutant strains of the M. tuberculosis complex unambiguously showed that M. tuberculosis induced a change in the FRET signal after 3 to 4 days of infection, indicating phagolysosomal rupture and cytosolic access. These effects were not seen for the strains M. tuberculosisDeltaRD1 or BCG, both lacking the ESX-1 secreted protein ESAT-6, which reportedly shows membrane-lysing properties. Complementation of these strains with the ESX-1 secretion system of M. tuberculosis restored the ability to cause phagolysosomal rupture. In addition, control experiments with the fish pathogen Mycobacterium marinum showed phagolysosomal translocation only for ESX-1 intact strains, further validating our experimental approach. Most importantly, for M. tuberculosis as well as for M. marinum we observed that phagolysosomal rupture was followed by necrotic cell death of the infected macrophages, whereas ESX-1 deletion- or truncation-mutants that remained enclosed within phagolysosomal compartments did not induce such cytotoxicity. Hence, we provide a novel mechanism how ESX-1 competent, virulent M. tuberculosis and M. marinum strains induce host cell death and thereby escape innate host defenses and favor their spread to new cells. In this respect, our results also open new research directions in relation with the extracellular localization of M. tuberculosis inside necrotic lesions that can now be tackled from a completely new perspective. PMID- 22319449 TI - Viral mediated redirection of NEMO/IKKgamma to autophagosomes curtails the inflammatory cascade. AB - The early host response to viral infections involves transient activation of pattern recognition receptors leading to an induction of inflammatory cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha). Subsequent activation of cytokine receptors in an autocrine and paracrine manner results in an inflammatory cascade. The precise mechanisms by which viruses avert an inflammatory cascade are incompletely understood. Nuclear factor (NF)-kappaB is a central regulator of the inflammatory signaling cascade that is controlled by inhibitor of NF-kappaB (IkappaB) proteins and the IkappaB kinase (IKK) complex. In this study we show that murine cytomegalovirus inhibits the inflammatory cascade by blocking Toll-like receptor (TLR) and IL-1 receptor dependent NF-kappaB activation. Inhibition occurs through an interaction of the viral M45 protein with the NF-kappaB essential modulator (NEMO), the regulatory subunit of the IKK complex. M45 induces proteasome-independent degradation of NEMO by targeting NEMO to autophagosomes for subsequent degradation in lysosomes. We propose that the selective and irreversible degradation of a central regulatory protein by autophagy represents a new viral strategy to dampen the inflammatory response. PMID- 22319450 TI - Biochemical properties of highly neuroinvasive prion strains. AB - Infectious prions propagate from peripheral entry sites into the central nervous system (CNS), where they cause progressive neurodegeneration that ultimately leads to death. Yet the pathogenesis of prion disease can vary dramatically depending on the strain, or conformational variant of the aberrantly folded and aggregated protein, PrP(Sc). Although most prion strains invade the CNS, some prion strains cannot gain entry and do not cause clinical signs of disease. The conformational basis for this remarkable variation in the pathogenesis among strains is unclear. Using mouse-adapted prion strains, here we show that highly neuroinvasive prion strains primarily form diffuse aggregates in brain and are noncongophilic, conformationally unstable in denaturing conditions, and lead to rapidly lethal disease. These neuroinvasive strains efficiently generate PrP(Sc) over short incubation periods. In contrast, the weakly neuroinvasive prion strains form large fibrillary plaques and are stable, congophilic, and inefficiently generate PrP(Sc) over long incubation periods. Overall, these results indicate that the most neuroinvasive prion strains are also the least stable, and support the concept that the efficient replication and unstable nature of the most rapidly converting prions may be a feature linked to their efficient spread into the CNS. PMID- 22319451 TI - A bacterial acetyltransferase destroys plant microtubule networks and blocks secretion. AB - The eukaryotic cytoskeleton is essential for structural support and intracellular transport, and is therefore a common target of animal pathogens. However, no phytopathogenic effector has yet been demonstrated to specifically target the plant cytoskeleton. Here we show that the Pseudomonas syringae type III secreted effector HopZ1a interacts with tubulin and polymerized microtubules. We demonstrate that HopZ1a is an acetyltransferase activated by the eukaryotic co factor phytic acid. Activated HopZ1a acetylates itself and tubulin. The conserved autoacetylation site of the YopJ / HopZ superfamily, K289, plays a critical role in both the avirulence and virulence function of HopZ1a. Furthermore, HopZ1a requires its acetyltransferase activity to cause a dramatic decrease in Arabidopsis thaliana microtubule networks, disrupt the plant secretory pathway and suppress cell wall-mediated defense. Together, this study supports the hypothesis that HopZ1a promotes virulence through cytoskeletal and secretory disruption. PMID- 22319452 TI - Reduction of NADPH-oxidase activity ameliorates the cardiovascular phenotype in a mouse model of Williams-Beuren Syndrome. AB - A hallmark feature of Williams-Beuren Syndrome (WBS) is a generalized arteriopathy due to elastin deficiency, presenting as stenoses of medium and large arteries and leading to hypertension and other cardiovascular complications. Deletion of a functional NCF1 gene copy has been shown to protect a proportion of WBS patients against hypertension, likely through reduced NADPH oxidase (NOX)-mediated oxidative stress. DD mice, carrying a 0.67 Mb heterozygous deletion including the Eln gene, presented with a generalized arteriopathy, hypertension, and cardiac hypertrophy, associated with elevated angiotensin II (angII), oxidative stress parameters, and Ncf1 expression. Genetic (by crossing with Ncf1 mutant) and/or pharmacological (with ang II type 1 receptor blocker, losartan, or NOX inhibitor apocynin) reduction of NOX activity controlled hormonal and biochemical parameters in DD mice, resulting in normalized blood pressure and improved cardiovascular histology. We provide strong evidence for implication of the redox system in the pathophysiology of the cardiovascular disease in a mouse model of WBS. The phenotype of these mice can be ameliorated by either genetic or pharmacological intervention reducing NOX activity, likely through reduced angII-mediated oxidative stress. Therefore, anti-NOX therapy merits evaluation to prevent the potentially serious cardiovascular complications of WBS, as well as in other cardiovascular disorders mediated by similar pathogenic mechanism. PMID- 22319453 TI - Evaluation of the role of functional constraints on the integrity of an ultraconserved region in the genus Drosophila. AB - Why gene order is conserved over long evolutionary timespans remains elusive. A common interpretation is that gene order conservation might reflect the existence of functional constraints that are important for organismal performance. Alteration of the integrity of genomic regions, and therefore of those constraints, would result in detrimental effects. This notion seems especially plausible in those genomes that can easily accommodate gene reshuffling via chromosomal inversions since genomic regions free of constraints are likely to have been disrupted in one or more lineages. Nevertheless, no empirical test has been performed to this notion. Here, we disrupt one of the largest conserved genomic regions of the Drosophila genome by chromosome engineering and examine the phenotypic consequences derived from such disruption. The targeted region exhibits multiple patterns of functional enrichment suggestive of the presence of constraints. The carriers of the disrupted collinear block show no defects in their viability, fertility, and parameters of general homeostasis, although their odorant perception is altered. This change in odorant perception does not correlate with modifications of the level of expression and sex bias of the genes within the genomic region disrupted. Our results indicate that even in highly rearranged genomes, like those of Diptera, unusually high levels of gene order conservation cannot be systematically attributed to functional constraints, which raises the possibility that other mechanisms can be in place and therefore the underpinnings of the maintenance of gene organization might be more diverse than previously thought. PMID- 22319454 TI - The Williams-Beuren Syndrome-a window into genetic variants leading to the development of cardiovascular disease. PMID- 22319455 TI - The mitochondrial chaperone protein TRAP1 mitigates alpha-Synuclein toxicity. AB - Overexpression or mutation of alpha-Synuclein is associated with protein aggregation and interferes with a number of cellular processes, including mitochondrial integrity and function. We used a whole-genome screen in the fruit fly Drosophila melanogaster to search for novel genetic modifiers of human [A53T]alpha-Synuclein-induced neurotoxicity. Decreased expression of the mitochondrial chaperone protein tumor necrosis factor receptor associated protein 1 (TRAP1) was found to enhance age-dependent loss of fly head dopamine (DA) and DA neuron number resulting from [A53T]alpha-Synuclein expression. In addition, decreased TRAP1 expression in [A53T]alpha-Synuclein-expressing flies resulted in enhanced loss of climbing ability and sensitivity to oxidative stress. Overexpression of human TRAP1 was able to rescue these phenotypes. Similarly, human TRAP1 overexpression in rat primary cortical neurons rescued [A53T]alpha Synuclein-induced sensitivity to rotenone treatment. In human (non)neuronal cell lines, small interfering RNA directed against TRAP1 enhanced [A53T]alpha Synuclein-induced sensitivity to oxidative stress treatment. [A53T]alpha Synuclein directly interfered with mitochondrial function, as its expression reduced Complex I activity in HEK293 cells. These effects were blocked by TRAP1 overexpression. Moreover, TRAP1 was able to prevent alteration in mitochondrial morphology caused by [A53T]alpha-Synuclein overexpression in human SH-SY5Y cells. These results indicate that [A53T]alpha-Synuclein toxicity is intimately connected to mitochondrial dysfunction and that toxicity reduction in fly and rat primary neurons and human cell lines can be achieved using overexpression of the mitochondrial chaperone TRAP1. Interestingly, TRAP1 has previously been shown to be phosphorylated by the serine/threonine kinase PINK1, thus providing a potential link of PINK1 via TRAP1 to alpha-Synuclein. PMID- 22319456 TI - Loss of function of the Cik1/Kar3 motor complex results in chromosomes with syntelic attachment that are sensed by the tension checkpoint. AB - The attachment of sister kinetochores by microtubules emanating from opposite spindle poles establishes chromosome bipolar attachment, which generates tension on chromosomes and is essential for sister-chromatid segregation. Syntelic attachment occurs when both sister kinetochores are attached by microtubules from the same spindle pole and this attachment is unable to generate tension on chromosomes, but a reliable method to induce syntelic attachments is not available in budding yeast. The spindle checkpoint can sense the lack of tension on chromosomes as well as detached kinetochores to prevent anaphase onset. In budding yeast Saccharomyces cerevisiae, tension checkpoint proteins Aurora/Ipl1 kinase and centromere-localized Sgo1 are required to sense the absence of tension but are dispensable for the checkpoint response to detached kinetochores. We have found that the loss of function of a motor protein complex Cik1/Kar3 in budding yeast leads to syntelic attachments. Inactivation of either the spindle or tension checkpoint enables premature anaphase entry in cells with dysfunctional Cik1/Kar3, resulting in co-segregation of sister chromatids. Moreover, the abolished Kar3-kinetochore interaction in cik1 mutants suggests that the Cik1/Kar3 complex mediates chromosome movement along microtubules, which could facilitate bipolar attachment. Therefore, we can induce syntelic attachments in budding yeast by inactivating the Cik1/Kar3 complex, and this approach will be very useful to study the checkpoint response to syntelic attachments. PMID- 22319457 TI - Down-regulating sphingolipid synthesis increases yeast lifespan. AB - Knowledge of the mechanisms for regulating lifespan is advancing rapidly, but lifespan is a complex phenotype and new features are likely to be identified. Here we reveal a novel approach for regulating lifespan. Using a genetic or a pharmacological strategy to lower the rate of sphingolipid synthesis, we show that Saccharomyces cerevisiae cells live longer. The longer lifespan is due in part to a reduction in Sch9 protein kinase activity and a consequent reduction in chromosomal mutations and rearrangements and increased stress resistance. Longer lifespan also arises in ways that are independent of Sch9 or caloric restriction, and we speculate on ways that sphingolipids might mediate these aspects of increased lifespan. Sch9 and its mammalian homolog S6 kinase work downstream of the target of rapamycin, TOR1, protein kinase, and play evolutionarily conserved roles in regulating lifespan. Our data establish Sch9 as a focal point for regulating lifespan by integrating nutrient signals from TOR1 with growth and stress signals from sphingolipids. Sphingolipids are found in all eukaryotes and our results suggest that pharmacological down-regulation of one or more sphingolipids may provide a means to reduce age-related diseases and increase lifespan in other eukaryotes. PMID- 22319458 TI - The empirical power of rare variant association methods: results from sanger sequencing in 1,998 individuals. AB - The role of rare genetic variation in the etiology of complex disease remains unclear. However, the development of next-generation sequencing technologies offers the experimental opportunity to address this question. Several novel statistical methodologies have been recently proposed to assess the contribution of rare variation to complex disease etiology. Nevertheless, no empirical estimates comparing their relative power are available. We therefore assessed the parameters that influence their statistical power in 1,998 individuals Sanger sequenced at seven genes by modeling different distributions of effect, proportions of causal variants, and direction of the associations (deleterious, protective, or both) in simulated continuous trait and case/control phenotypes. Our results demonstrate that the power of recently proposed statistical methods depend strongly on the underlying hypotheses concerning the relationship of phenotypes with each of these three factors. No method demonstrates consistently acceptable power despite this large sample size, and the performance of each method depends upon the underlying assumption of the relationship between rare variants and complex traits. Sensitivity analyses are therefore recommended to compare the stability of the results arising from different methods, and promising results should be replicated using the same method in an independent sample. These findings provide guidance in the analysis and interpretation of the role of rare base-pair variation in the etiology of complex traits and diseases. PMID- 22319459 TI - Raf1 Is a DCAF for the Rik1 DDB1-like protein and has separable roles in siRNA generation and chromatin modification. AB - Non-coding transcription can trigger histone post-translational modifications forming specialized chromatin. In fission yeast, heterochromatin formation requires RNAi and the histone H3K9 methyltransferase complex CLRC, composed of Clr4, Raf1, Raf2, Cul4, and Rik1. CLRC mediates H3K9 methylation and siRNA production; it also displays E3-ubiquitin ligase activity in vitro. DCAFs act as substrate receptors for E3 ligases and may couple ubiquitination with histone methylation. Here, structural alignment and mutation of signature WDxR motifs in Raf1 indicate that it is a DCAF for CLRC. We demonstrate that Raf1 promotes H3K9 methylation and siRNA amplification via two distinct, separable functions. The association of the DCAF Raf1 with Cul4-Rik1 is critical for H3K9 methylation, but dispensable for processing of centromeric transcripts into siRNAs. Thus the association of a DCAF, Raf1, with its adaptor, Rik1, is required for histone methylation and to allow RNAi to signal to chromatin. PMID- 22319460 TI - Inter-homolog crossing-over and synapsis in Arabidopsis meiosis are dependent on the chromosome axis protein AtASY3. AB - In this study we have analysed AtASY3, a coiled-coil domain protein that is required for normal meiosis in Arabidopsis. Analysis of an Atasy3-1 mutant reveals that loss of the protein compromises chromosome axis formation and results in reduced numbers of meiotic crossovers (COs). Although the frequency of DNA double-strand breaks (DSBs) appears moderately reduced in Atasy3-1, the main recombination defect is a reduction in the formation of COs. Immunolocalization studies in wild-type meiocytes indicate that the HORMA protein AtASY1, which is related to Hop1 in budding yeast, forms hyper-abundant domains along the chromosomes that are spatially associated with DSBs and early recombination pathway proteins. Loss of AtASY3 disrupts the axial organization of AtASY1. Furthermore we show that the AtASY3 and AtASY1 homologs BoASY3 and BoASY1, from the closely related species Brassica oleracea, are co-immunoprecipitated from meiocyte extracts and that AtASY3 interacts with AtASY1 via residues in its predicted coiled-coil domain. Together our results suggest that AtASY3 is a functional homolog of Red1. Since studies in budding yeast indicate that Red1 and Hop1 play a key role in establishing a bias to favor inter-homolog recombination (IHR), we propose that AtASY3 and AtASY1 may have a similar role in Arabidopsis. Loss of AtASY3 also disrupts synaptonemal complex (SC) formation. In Atasy3-1 the transverse filament protein AtZYP1 forms small patches rather than a continuous SC. The few AtMLH1 foci that remain in Atasy3-1 are found in association with the AtZYP1 patches. This is sufficient to prevent the ectopic recombination observed in the absence of AtZYP1, thus emphasizing that in addition to its structural role the protein is important for CO formation. PMID- 22319461 TI - Kurtosis-based blind source extraction of complex non-circular signals with application in EEG artifact removal in real-time. AB - A new class of complex domain blind source extraction algorithms suitable for the extraction of both circular and non-circular complex signals is proposed. This is achieved through sequential extraction based on the degree of kurtosis and in the presence of non-circular measurement noise. The existence and uniqueness analysis of the solution is followed by a study of fast converging variants of the algorithm. The performance is first assessed through simulations on well understood benchmark signals, followed by a case study on real-time artifact removal from EEG signals, verified using both qualitative and quantitative metrics. The results illustrate the power of the proposed approach in real-time blind extraction of general complex-valued sources. PMID- 22319462 TI - Social Anxiety Modulates Risk Sensitivity through Activity in the Anterior Insula. AB - Decision neuroscience offers the potential for decomposing differences in behavior across individuals into components of valuation intimately tied to brain function. One application of this approach lies in novel conceptualizations of behavioral attributes that are aberrant in psychiatric disorders. We investigated the relationship between social anxiety and behavior in a novel socially determined risk task. Behaviorally, higher scores on a social phobia inventory (SPIN) among healthy participants were associated with an increase in risky responses. Furthermore, activity in a region of the dorsal anterior insula (dAI) scaled in proportion to SPIN score in risky versus non-risky choices. This region of the insula was functionally connected to areas in the intraparietal sulcus and anterior cingulate cortex that were related to decision-making across all participants. Overall, social anxiety was associated with decreased risk aversion in our task, consistent with previous results investigating risk taking in many everyday behaviors. Moreover, this difference was linked to the anterior insula, a region commonly implicated in risk attitudes and socio-emotional processes. PMID- 22319463 TI - Risk, reward, and decision-making in a rodent model of cognitive aging. AB - Impaired decision-making in aging can directly impact factors (financial security, health care) that are critical to maintaining quality of life and independence at advanced ages. Naturalistic rodent models mimic human aging in other cognitive domains, and afford the opportunity to parse the effects of age on discrete aspects of decision-making in a manner relatively uncontaminated by experiential factors. Young adult (5-7 months) and aged (23-25 months) male F344 rats were trained on a probability discounting task in which they made discrete trial choices between a small certain reward (one food pellet) and a large but uncertain reward (two food pellets with varying probabilities of delivery ranging from 100 to 0%). Young rats chose the large reward when it was associated with a high probability of delivery and shifted to the small but certain reward as probability of the large reward decreased. As a group, aged rats performed comparably to young, but there was significantly greater variance among aged rats. One subgroup of aged rats showed strong preference for the small certain reward. This preference was maintained under conditions in which large reward delivery was also certain, suggesting decreased sensitivity to reward magnitude. In contrast, another subgroup of aged rats showed strong preference for the large reward at low probabilities of delivery. Interestingly, this subgroup also showed elevated preference for probabilistic rewards when reward magnitudes were equalized. Previous findings using this same aged study population described strongly attenuated discounting of delayed rewards with age, together suggesting that a subgroup of aged rats may have deficits associated with accounting for reward costs (i.e., delay or probability). These deficits in cost-accounting were dissociable from the age-related differences in sensitivity to reward magnitude, suggesting that aging influences multiple, distinct mechanisms that can impact cost-benefit decision-making. PMID- 22319464 TI - Switching between Manual Control and Brain-Computer Interface Using Long Term and Short Term Quality Measures. AB - Assistive devices for persons with limited motor control translate or amplify remaining functions to allow otherwise impossible actions. These assistive devices usually rely on just one type of input signal which can be derived from residual muscle functions or any other kind of biosignal. When only one signal is used, the functionality of the assistive device can be reduced as soon as the quality of the provided signal is impaired. The quality can decrease in case of fatigue, lack of concentration, high noise, spasms, tremors, depending on the type of signal. To overcome this dependency on one input signal, a combination of more inputs should be feasible. This work presents a hybrid Brain-Computer Interface (hBCI) approach where two different input signals (joystick and BCI) were monitored and only one of them was chosen as a control signal at a time. Users could move a car in a game-like feedback application to collect coins and avoid obstacles via either joystick or BCI control. Both control types were constantly monitored with four different long term quality measures to evaluate the current state of the signals. As soon as the quality dropped below a certain threshold, a monitoring system would switch to the other control mode and vice versa. Additionally, short term quality measures were applied to check for strong artifacts that could render voluntary control impossible. These measures were used to prohibit actions carried out during times when highly uncertain signals were recorded. The switching possibility allowed more functionality for the users. Moving the car was still possible even after one control mode was not working any more. The proposed system serves as a basis that shows how BCI can be used as an assistive device, especially in combination with other assistive technology. PMID- 22319465 TI - Learning to select actions with spiking neurons in the Basal Ganglia. AB - We expand our existing spiking neuron model of decision making in the cortex and basal ganglia to include local learning on the synaptic connections between the cortex and striatum, modulated by a dopaminergic reward signal. We then compare this model to animal data in the bandit task, which is used to test rodent learning in conditions involving forced choice under rewards. Our results indicate a good match in terms of both behavioral learning results and spike patterns in the ventral striatum. The model successfully generalizes to learning the utilities of multiple actions, and can learn to choose different actions in different states. The purpose of our model is to provide both high-level behavioral predictions and low-level spike timing predictions while respecting known neurophysiology and neuroanatomy. PMID- 22319467 TI - GSK-3 and Wnt Signaling in Neurogenesis and Bipolar Disorder. AB - The canonical Wnt signaling pathway is critical for development of the mammalian central nervous system and regulates diverse processes throughout adulthood, including adult neurogenesis. Glycogen synthase kinase-3 (GSK-3) antagonizes the canonical Wnt pathway and therefore also plays a central role in neural development and adult neurogenesis. Lithium, the first line of therapy for bipolar disorder, inhibits GSK-3, activates Wnt signaling and stimulates adult neurogenesis, which may be important for its therapeutic effects. GSK-3 also regulates other critical signaling pathways which may contribute to the therapeutic effects of lithium, including growth factor/neurotrophin signaling downstream of Akt. Here we will review the roles of GSK-3 in CNS development and adult neurogenesis, with a focus on the canonical Wnt pathway. We will also discuss the validation of GSK-3 as the relevant target of lithium and the mechanisms downstream of GSK-3 that influence mammalian behavior. PMID- 22319468 TI - Selective Changes of GABA(A) Channel Subunit mRNAs in the Hippocampus and Orbitofrontal Cortex but not in Prefrontal Cortex of Human Alcoholics. AB - Alcohol dependence is a common chronic relapsing disorder. The development of alcohol dependence has been associated with changes in brain GABA(A) channel mediated neurotransmission and plasticity. We have examined mRNA expression of the GABA(A) channel subunit genes in three brain regions in individuals with or without alcohol dependence using quantitative real-time PCR assay. The levels of selective GABA(A) channel subunit mRNAs were altered in specific brain regions in alcoholic subjects. Significant increase in the alpha1, alpha4, alpha5, beta1, and gamma1 subunit mRNAs in the hippocampal dentate gyrus region, and decrease in the beta2 and delta subunit mRNAs in the orbitofrontal cortex were identified whereas no changes in the dorsolateral prefrontal cortex were detected. The data increase our understanding of the role of GABA(A) channels in the development of alcohol dependence. PMID- 22319466 TI - gp130 cytokines are positive signals triggering changes in gene expression and axon outgrowth in peripheral neurons following injury. AB - Adult peripheral neurons, in contrast to adult central neurons, are capable of regeneration after axonal damage. Much attention has focused on the changes that accompany this regeneration in two places, the distal nerve segment (where phagocytosis of axonal debris, changes in the surface properties of Schwann cells, and induction of growth factors and cytokines occur) and the neuronal cell body (where dramatic changes in cell morphology and gene expression occur). The changes in the axotomized cell body are often referred to as the "cell body response." The focus of the current review is a family of cytokines, the glycoprotein 130 (gp130) cytokines, which produce their actions through a common gp130 signaling receptor and which function as injury signals for axotomized peripheral neurons, triggering changes in gene expression and in neurite outgrowth. These cytokines play important roles in the responses of sympathetic, sensory, and motor neurons to injury. The best studied of these cytokines in this context are leukemia inhibitory factor (LIF) and interleukin (IL)-6, but experiments with conditional gp130 knockout animals suggest that other members of this family, not yet determined, are also involved. The primary gp130 signaling pathway shown to be involved is the activation of Janus kinase (JAK) and the transcription factors Signal Transducers and Activators of Transcription (STAT), though other downstream pathways such as mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) may also play a role. gp130 signaling may involve paracrine, retrograde, and autocrine actions of these cytokines. Recent studies suggest that manipulation of this cytokine system can also stimulate regeneration by injured central neurons. PMID- 22319469 TI - State-dependent modulation of gap junction signaling by the persistent sodium current. AB - THALAMIC NEURONS FLUCTUATE BETWEEN TWO STATES: a hyperpolarized state associated with burst firing and sleep spindles, and a depolarized state associated with tonic firing and rapid, reliable information transmission between the sensory periphery and cortex. The thalamic reticular nucleus (TRN) plays a central role in thalamocortical processing by providing feed-forward and feedback inhibition to thalamic relay cells; TRN cells participate in the generation of sleep spindles, and have been suggested to focus the neural "searchlight" of attention. The mechanisms underlying synchrony in the TRN during different behavioral states are largely unknown. TRN cells are densely interconnected by electrical synapses. Here we show that activation of the persistent sodium current (I(NaP)) by depolarization causes up to fourfold changes in electrical synaptic efficacy between TRN neurons. We further show that amplification of electrical synaptic responses strongly enhances tonic spike synchrony but, surprisingly, does not affect burst coordination. We use a Hodgkin-Huxley model to gain insight into the differences between the effects of burstlets, spikelets, and amplification on burst and spike times. PMID- 22319470 TI - Intracerebral transplantation for neurological disorders. Lessons from developmental, experimental, and clinical studies. AB - The use of human pluripotent stem cells (PSCs) for cell therapy faces a number of challenges that are progressively answered by results from clinical trials and experimental research. Among these is the control of differentiation before transplantation and the prediction of cell fate after administration into the human brain, two aspects that condition both the safety and efficacy of the approach. For neurological disorders, this includes two steps: firstly, the identification of the optimal maturation stage for transplantation along the continuum that transforms PSCs into fully differentiated neural cell types, together with the derivation of robust protocols for large-scale production of biological products, and, secondly, the understanding of the effects of environmental cues and their possible interference with transplanted cells commitment. This review will firstly summarize our knowledge on developmental processes that have been applied to achieve robust in vitro differentiation of PSCs into neural progenitors. In a second part, we summarize results from experimental and clinical transplantation studies that help understanding the dialogue that establishes between transplanted cells and their host brain. PMID- 22319471 TI - GABA Potency at GABA(A) Receptors Found in Synaptic and Extrasynaptic Zones. AB - The potency of GABA is vitally important for its primary role in activating GABA(A) receptors and acting as an inhibitory neurotransmitter. Although numerous laboratories have presented information, directly or indirectly, on GABA potency, it is often difficult to compare across such studies given the inevitable variations in the methods used, the cell types studied, whether native or recombinant receptors are examined, and their relevance to native synaptic and extrasynaptic GABA(A) receptors. In this review, we list the most relevant isoforms of synaptic and extrasynaptic GABA(A) receptors that are thought to assemble in surface membranes of neurons in the central nervous system. Using consistent methodology in one cell type, the potencies of the endogenous neurotransmitter GABA are compared across a spectrum of GABA(A) receptors. The highest potency for GABA is measured when activating extrasynaptic-type alpha6 subunit-containing receptors, whereas synaptic-type alpha2beta3gamma2 and alpha3beta3gamma2 receptors exhibited the lowest potency, and other GABA(A) receptor subtypes that are found both in synaptic and extrasynaptic compartments, showed intermediate sensitivities to GABA. The relatively simple potency relationship between GABA and its target receptors is important as it serves as one of the major determinants of GABA(A) receptor activation, with consequences for the development of inhibition, either by tonic or phasic mechanisms. PMID- 22319472 TI - GABA Not Only a Neurotransmitter: Osmotic Regulation by GABA(A)R Signaling. AB - Mature macroglia and almost all neural progenitor types express gamma aminobutyric (GABA) A receptors (GABA(A)Rs), whose activation by ambient or synaptic GABA, leads to influx or efflux of chloride (Cl(-)) depending on its electro-chemical gradient (E(Cl)). Since the flux of Cl(-) is indissolubly associated to that of osmotically obliged water, GABA(A)Rs regulate water movements by modulating ion gradients. In addition, since water movements also occur through specialized water channels and transporters, GABA(A)R signaling could affect the movement of water by regulating the function of the channels and transporters involved, thereby affecting not only the direction of the water fluxes but also their dynamics. We will here review recent observations indicating that in neural cells GABA(A)R-mediated osmotic regulation affects the cellular volume thereby activating multiple intracellular signaling mechanisms important for cell proliferation, maturation, and survival. In addition, we will discuss evidence that the osmotic regulation exerted by GABA may contribute to brain water homeostasis in physiological and in pathological conditions causing brain edema, in which the GABAergic transmission is often altered. PMID- 22319473 TI - The reciprocal regulation of stress hormones and GABA(A) receptors. AB - Stress-derived steroid hormones regulate the expression and function of GABA(A) receptors (GABA(A)Rs). Changes in GABA(A)R subunit expression have been demonstrated under conditions of altered steroid hormone levels, such as stress, as well as following exogenous steroid hormone administration. In addition to the effects of stress-derived steroid hormones on GABA(A)R subunit expression, stress hormones can also be metabolized to neuroactive derivatives which can alter the function of GABA(A)Rs. Neurosteroids allosterically modulate GABA(A)Rs at concentrations comparable to those during stress. In addition to the actions of stress-derived steroid hormones on GABA(A)Rs, GABA(A)Rs reciprocally regulate the production of stress hormones. The stress response is mediated by the hypothalamic-pituitary-adrenal (HPA) axis, the activity of which is governed by corticotropin releasing hormone (CRH) neurons. The activity of CRH neurons is largely controlled by robust GABAergic inhibition. Recently, it has been demonstrated that CRH neurons are regulated by neurosteroid-sensitive, GABA(A)R delta subunit-containing receptors representing a novel feedback mechanism onto the HPA axis. Further, it has been demonstrated that neurosteroidogenesis and neurosteroid actions on GABA(A)R delta subunit-containing receptors on CRH neurons are necessary to mount the physiological response to stress. Here we review the literature describing the effects of steroid hormones on GABA(A)Rs as well as the importance of GABA(A)Rs in regulating the production of steroid hormones. This review incorporates what we currently know about changes in GABA(A)Rs following stress and the role in HPA axis regulation. PMID- 22319474 TI - Cell-type specific regulation of cortical excitability through the allatostatin receptor system. AB - Recent technical advances enable the regulation of neuronal circuit activity with high spatial and temporal resolution through genetic delivery of molecular activation or inactivation systems.Among them, the allatostatin receptor (AlstR)/ligand system has been developed for selective and quickly reversible silencing of mammalian neurons. However, targeted AlstR-mediated inactivation of specific neuronal types, particularly diverse types of inhibitory interneurons, remains to be established. In the present study, we achieved Cre-directed expression of AlstRs to excitatory and inhibitory cell-types in the cortex, and found that the AlstR-mediated inactivation was specific and robust at single-cell and neuronal population levels. Bath application of the allatostatin peptide markedly reduced spiking activity of AlstR-expressing excitatory and inhibitory neurons in response to intrasomatic current injections and laser photostimulation via glutamate uncaging, but control neurons without AlstR expression were not affected. As for the cortical network activity, the peptide application constrained photostimulation-evoked excitatory activity propagation detected by fast voltage-sensitive dye (VSD) imaging of the slices expressing AlstRs selectively in excitatory neurons, while it augmented excitatory activity in those slices with inhibitory neurons expressing AlstRs. In addition, AlstR mediated inactivation effectively suppressed pharmacologically induced seizure activity in the slices targeting AlstRs to excitatory neurons. Taken together, our work demonstrated that the genetic delivery of AlstRs can be used for regulation of cortical excitability in a cell-type specific manner, and suggested that the AlstR system can be potentially used for fast seizure control. PMID- 22319475 TI - Human Processing of Short Temporal Intervals as Revealed by an ERP Waveform Analysis. AB - To clarify the time course over which the human brain processes information about durations up to ~300 ms, we reanalyzed the data that were previously reported by Mitsudo et al. (2009) using a multivariate analysis method. Event-related potentials were recorded from 19 scalp electrodes on 11 (nine original and two additional) participants while they judged whether two neighboring empty time intervals - called t1 and t2 and marked by three tone bursts - had equal durations. There was also a control condition in which the participants were presented the same temporal patterns but without a judgment task. In the present reanalysis, we sought to visualize how the temporal patterns were represented in the brain over time. A correlation matrix across channels was calculated for each temporal pattern. Geometric separations between the correlation matrices were calculated, and subjected to multidimensional scaling. We performed such analyses for a moving 100-ms time window after the t1 presentations. In the windows centered at <100 ms after the t2 presentation, the analyses revealed the local maxima of categorical separation between temporal patterns of perceptually equal durations versus perceptually unequal durations, both in the judgment condition and in the control condition. Such categorization of the temporal patterns was prominent only in narrow temporal regions. The analysis indicated that the participants determined whether the two neighboring time intervals were of equal duration mostly within 100 ms after the presentation of the temporal patterns. A very fast brain activity was related to the perception of elementary temporal patterns without explicit judgments. This is consistent with the findings of Mitsudo et al. and it is in line with the processing time hypothesis proposed by Nakajima et al. (2004). The validity of the correlation matrix analyses turned out to be an effective tool to grasp the overall responses of the brain to temporal patterns. PMID- 22319476 TI - Sex differences in counting and timing. PMID- 22319477 TI - A unified model of time perception accounts for duration-based and beat-based timing mechanisms. AB - Accurate timing is an integral aspect of sensory and motor processes such as the perception of speech and music and the execution of skilled movement. Neuropsychological studies of time perception in patient groups and functional neuroimaging studies of timing in normal participants suggest common neural substrates for perceptual and motor timing. A timing system is implicated in core regions of the motor network such as the cerebellum, inferior olive, basal ganglia, pre-supplementary, and supplementary motor area, pre-motor cortex as well as higher-level areas such as the prefrontal cortex. In this article, we assess how distinct parts of the timing system subserve different aspects of perceptual timing. We previously established brain bases for absolute, duration based timing and relative, beat-based timing in the olivocerebellar and striato thalamo-cortical circuits respectively (Teki et al., 2011). However, neurophysiological and neuroanatomical studies provide a basis to suggest that timing functions of these circuits may not be independent. Here, we propose a unified model of time perception based on coordinated activity in the core striatal and olivocerebellar networks that are interconnected with each other and the cerebral cortex through multiple synaptic pathways. Timing in this unified model is proposed to involve serial beat-based striatal activation followed by absolute olivocerebellar timing mechanisms. PMID- 22319478 TI - Sleep, circadian rhythms, and interval timing: evolutionary strategies to time information. PMID- 22319479 TI - A novel, variable angle guide grid for neuronal activity studies. AB - INTRODUCTION: Surgically implanted chambers with removable grids are routinely used for studying patterns of neuronal activity in primate brains; however, accessing target tissues is significantly constrained by standard grid designs. Typically, grids are configured with a series of guide holes drilled vertically, parallel to the walls of the chamber, thus targeted sites are limited to those in line vertically with one of the guide holes. METHODS: By using the three dimensional modeling software, a novel grid was designed to reach the targeted sites far beyond the standard reach of the chamber. The grid was fabricated using conventional machining techniques and three-dimensional printing. RESULTS: A pilot study involving microinjection of the magnetic resonance (MR) contrast agent gadolinium into the discrete regions of interest (ROIs) in the temporal cortex of an awake, behaving monkey demonstrated the effectiveness of this new design of the guide grid. Using multiple different angles of approach, we were readily able to access 10 injection sites, which were up to 5 mm outside the traditional, orthogonal reach of the chamber. PMID- 22319480 TI - Why the Transitivity of Perceptual Simultaneity Should be Taken Seriously. PMID- 22319481 TI - Molecular mechanisms underlying memory consolidation of taste information in the cortex. AB - The senses of taste and odor are both chemical senses. However, whereas an organism can detect an odor at a relatively long distance from its source, taste serves as the ultimate proximate gatekeeper of food intake: it helps in avoiding poisons and consuming beneficial substances. The automatic reaction to a given taste has been developed during evolution and is well adapted to conditions that may occur with high probability during the lifetime of an organism. However, in addition to this automatic reaction, animals can learn and remember tastes, together with their positive or negative values, with high precision and in light of minimal experience. This ability of mammalians to learn and remember tastes has been studied extensively in rodents through application of reasonably simple and well defined behavioral paradigms. The learning process follows a temporal continuum similar to those of other memories: acquisition, consolidation, retrieval, relearning, and reconsolidation. Moreover, inhibiting protein synthesis in the gustatory cortex (GC) specifically affects the consolidation phase of taste memory, i.e., the transformation of short- to long-term memory, in keeping with the general biochemical definition of memory consolidation. This review aims to present a general background of taste learning, and to focus on recent findings regarding the molecular mechanisms underlying taste-memory consolidation in the GC. Specifically, the roles of neurotransmitters, neuromodulators, immediate early genes, and translation regulation are addressed. PMID- 22319482 TI - Increased Entorhinal-Prefrontal Theta Synchronization Parallels Decreased Entorhinal-Hippocampal Theta Synchronization during Learning and Consolidation of Associative Memory. AB - Memories are thought to be encoded as a distributed representation in the neocortex. The medial prefrontal cortex (mPFC) has been shown to support the expression of memories that initially depend on the hippocampus (HPC), yet the mechanisms by which the HPC and mPFC access the distributed representations in the neocortex are unknown. By measuring phase synchronization of local field potential (LFP) oscillations, we found that learning initiated changes in neuronal communication of the HPC and mPFC with the lateral entorhinal cortex (LEC), an area that is connected with many other neocortical regions. LFPs were recorded simultaneously from the three brain regions while rats formed an association between an auditory stimulus (CS) and eyelid stimulation (US) in a trace eyeblink conditioning paradigm, as well as during retention 1 month following learning. Over the course of learning, theta oscillations in the LEC and mPFC became strongly synchronized following presentation of the CS on trials in which rats exhibited a conditioned response (CR), and this strengthened synchronization was also observed during remote retention. In contrast, CS-evoked theta synchronization between the LEC and HPC decreased with learning. Our results suggest that communication between the LEC and mPFC are strengthened with learning whereas the communication between the LEC and HPC are concomitantly weakened, suggesting that enhanced LEC-mPFC communication may be a neuronal correlate for theoretically proposed neocortical reorganization accompanying encoding and consolidation of a memory. PMID- 22319483 TI - Onset rivalry: the initial dominance phase is independent of ongoing perceptual alternations. AB - Binocular rivalry has been used to study a wide range of visual processes, from the integration of low-level features to the selection of signals that reach awareness. However, many of these studies do not distinguish between early and late phases of rivalry. There is clear evidence that the "onset" stage of rivalry is characterized by stable, yet idiosyncratic biases that are not evident in the average dominance of sustained rivalry viewing. Low-level stimulus features also have robust effects in the onset phase that are not seen in sustained rivalry, suggesting these phases may be driven at least partly by different neural mechanisms. The effects of high-level cognitive and affective factors at onset are less clear but also show differences from their effects in sustained viewing. These findings have important implications for the interpretation of any rivalry experiments using brief presentation paradigms and for understanding how the brain copes with binocular discrepancies in natural viewing conditions in which our eyes constantly move around an ever-changing environment. This review will summarize current research and explore the factors influencing this "onset" stage. PMID- 22319484 TI - Quantities, amounts, and the numerical core system. PMID- 22319485 TI - Baseline gamma power during auditory steady-state stimulation in schizophrenia. AB - Several studies have reported deficits in gamma oscillatory activity elicited by sensory stimulation or cognitive processes in schizophrenia patients (SZ) compared to healthy control subjects (HC). However, the evidence for cortical hyperexcitability and reduced function of N-methyl-D-aspartate receptors (NMDARs) on parvalbumin-expressing inhibitory interneurons in schizophrenia leads to the prediction that gamma activity should rather be increased in SZ, but data supporting this hypothesis have been lacking. One possibility is that baseline induced gamma power is increased, an effect that might have gone unnoticed in studies of stimulus-locked oscillations. Here we addressed this question by re analyzing the data from a previously published study on the 40 Hz auditory steady state response (ASSR) in schizophrenia in which dipole source localization was used to examine gamma responses in the left and right auditory cortices. Subjects were 16 HC and 18 chronic SZ, who listened to trains of clicks presented at 40 Hz during electroencephalogram recording. Independent component analysis was used to remove ocular artifacts. Power spectra were computed for the pre-stimulus baseline period. We found that baseline power was higher in SZ than HC at 40 Hz in the left auditory cortex. Baseline 40 Hz power in the left auditory cortex was also correlated with ASSR evoked power in SZ. Thus, gamma oscillation abnormalities in schizophrenia may include abnormal increases in baseline power as well as deficits in evoked oscillations. These baseline increases could be the sign of NMDAR hypofunction on parvalbumin-expressing inhibitory interneurons, which would be consistent with acute NMDAR antagonism and genetic ablation models of schizophrenia. PMID- 22319486 TI - A statistical description of neural ensemble dynamics. AB - The growing use of multi-channel neural recording techniques in behaving animals has produced rich datasets that hold immense potential for advancing our understanding of how the brain mediates behavior. One limitation of these techniques is they do not provide important information about the underlying anatomical connections among the recorded neurons within an ensemble. Inferring these connections is often intractable because the set of possible interactions grows exponentially with ensemble size. This is a fundamental challenge one confronts when interpreting these data. Unfortunately, the combination of expert knowledge and ensemble data is often insufficient for selecting a unique model of these interactions. Our approach shifts away from modeling the network diagram of the ensemble toward analyzing changes in the dynamics of the ensemble as they relate to behavior. Our contribution consists of adapting techniques from signal processing and Bayesian statistics to track the dynamics of ensemble data on time scales comparable with behavior. We employ a Bayesian estimator to weigh prior information against the available ensemble data, and use an adaptive quantization technique to aggregate poorly estimated regions of the ensemble data space. Importantly, our method is capable of detecting changes in both the magnitude and structure of correlations among neurons missed by firing rate metrics. We show that this method is scalable across a wide range of time-scales and ensemble sizes. Lastly, the performance of this method on both simulated and real ensemble data is used to demonstrate its utility. PMID- 22319487 TI - Mitral cell spike synchrony modulated by dendrodendritic synapse location. AB - On their long lateral dendrites, mitral cells of the olfactory bulb form dendrodendritic synapses with large populations of granule cell interneurons. The mitral-granule cell microcircuit operating through these reciprocal synapses has been implicated in inducing synchrony between mitral cells. However, the specific mechanisms of mitral cell synchrony operating through this microcircuit are largely unknown and are complicated by the finding that distal inhibition on the lateral dendrites does not modulate mitral cell spikes. In order to gain insight into how this circuit synchronizes mitral cells within its spatial constraints, we built on a reduced circuit model of biophysically realistic multi-compartment mitral and granule cells to explore systematically the roles of dendrodendritic synapse location and mitral cell separation on synchrony. The simulations showed that mitral cells can synchronize when separated at arbitrary distances through a shared set of granule cells, but synchrony is optimally attained when shared granule cells form two balanced subsets, each subset clustered near to a soma of the mitral cell pairs. Another constraint for synchrony is that the input magnitude must be balanced. When adjusting the input magnitude driving a particular mitral cell relative to another, the mitral-granule cell circuit served to normalize spike rates of the mitral cells while inducing a phase shift or delay in the more weakly driven cell. This shift in phase is absent when the granule cells are removed from the circuit. Our results indicate that the specific distribution of dendrodendritic synaptic clusters is critical for optimal synchronization of mitral cell spikes in response to their odor input. PMID- 22319488 TI - Simulation of cholinergic and noradrenergic modulation of behavior in uncertain environments. AB - Attention is a complex neurobiological process that involves rapidly and flexibly balancing sensory input and goal-directed predictions in response to environmental changes. The cholinergic and noradrenergic systems, which have been proposed to respond to expected and unexpected environmental uncertainty, respectively, play an important role in attention by differentially modulating activity in a multitude of cortical targets. Here we develop a model of an attention task that involves expected and unexpected uncertainty. The cholinergic and noradrenergic systems track this uncertainty and, in turn, influence cortical processing in five different, experimentally verified ways: (1) nicotinic enhancement of thalamocortical input, (2) muscarinic regulation of corticocortical feedback, (3) noradrenergic mediation of a network reset, (4) locus coeruleus (LC) activation of the basal forebrain (BF), and (5) cholinergic and noradrenergic balance between sensory input and frontal cortex predictions. Our results shed light on how the noradrenergic and cholinergic systems interact with each other and a distributed set of neural areas, and how this could lead to behavioral adaptation in the face of uncertainty. PMID- 22319489 TI - LORIS: a web-based data management system for multi-center studies. AB - Longitudinal Online Research and Imaging System (LORIS) is a modular and extensible web-based data management system that integrates all aspects of a multi-center study: from heterogeneous data acquisition (imaging, clinical, behavior, and genetics) to storage, processing, and ultimately dissemination. It provides a secure, user-friendly, and streamlined platform to automate the flow of clinical trials and complex multi-center studies. A subject-centric internal organization allows researchers to capture and subsequently extract all information, longitudinal or cross-sectional, from any subset of the study cohort. Extensive error-checking and quality control procedures, security, data management, data querying, and administrative functions provide LORIS with a triple capability (1) continuous project coordination and monitoring of data acquisition (2) data storage/cleaning/querying, (3) interface with arbitrary external data processing "pipelines." LORIS is a complete solution that has been thoroughly tested through a full 10 year life cycle of a multi-center longitudinal project and is now supporting numerous international neurodevelopment and neurodegeneration research projects. PMID- 22319490 TI - PLDAPS: A Hardware Architecture and Software Toolbox for Neurophysiology Requiring Complex Visual Stimuli and Online Behavioral Control. AB - Neurophysiological studies in awake, behaving primates (both human and non-human) have focused with increasing scrutiny on the temporal relationship between neural signals and behaviors. Consequently, laboratories are often faced with the problem of developing experimental equipment that can support data recording with high temporal precision and also be flexible enough to accommodate a wide variety of experimental paradigms. To this end, we have developed a MATLAB toolbox that integrates several modern pieces of equipment, but still grants experimenters the flexibility of a high-level programming language. Our toolbox takes advantage of three popular and powerful technologies: the Plexon apparatus for neurophysiological recordings (Plexon, Inc., Dallas, TX, USA), a Datapixx peripheral (Vpixx Technologies, Saint-Bruno, QC, Canada) for control of analog, digital, and video input-output signals, and the Psychtoolbox MATLAB toolbox for stimulus generation (Brainard, 1997; Pelli, 1997; Kleiner et al., 2007). The PLDAPS ("Platypus") system is designed to support the study of the visual systems of awake, behaving primates during multi-electrode neurophysiological recordings, but can be easily applied to other related domains. Despite its wide range of capabilities and support for cutting-edge video displays and neural recording systems, the PLDAPS system is simple enough for someone with basic MATLAB programming skills to design their own experiments. PMID- 22319491 TI - Glomerular latency coding in artificial olfaction. AB - Sensory perception results from the way sensory information is subsequently transformed in the brain. Olfaction is a typical example in which odor representations undergo considerable changes as they pass from olfactory receptor neurons (ORNs) to second-order neurons. First, many ORNs expressing the same receptor protein yet presenting heterogeneous dose-response properties converge onto individually identifiable glomeruli. Second, onset latency of glomerular activation is believed to play a role in encoding odor quality and quantity in the context of fast information processing. Taking inspiration from the olfactory pathway, we designed a simple yet robust glomerular latency coding scheme for processing gas sensor data. The proposed bio-inspired approach was evaluated using an in-house SnO(2) sensor array. Glomerular convergence was achieved by noting the possible analogy between receptor protein expressed in ORNs and metal catalyst used across the fabricated gas sensor array. Ion implantation was another technique used to account both for sensor heterogeneity and enhanced sensitivity. The response of the gas sensor array was mapped into glomerular latency patterns, whose rank order is concentration-invariant. Gas recognition was achieved by simply looking for a "match" within a library of spatio-temporal spike fingerprints. Because of its simplicity, this approach enables the integration of sensing and processing onto a single-chip. PMID- 22319492 TI - Sensor selection and chemo-sensory optimization: toward an adaptable chemo sensory system. AB - Over the past two decades, despite the tremendous research on chemical sensors and machine olfaction to develop micro-sensory systems that will accomplish the growing existent needs in personal health (implantable sensors), environment monitoring (widely distributed sensor networks), and security/threat detection (chemo/bio warfare agents), simple, low-cost molecular sensing platforms capable of long-term autonomous operation remain beyond the current state-of-the-art of chemical sensing. A fundamental issue within this context is that most of the chemical sensors depend on interactions between the targeted species and the surfaces functionalized with receptors that bind the target species selectively, and that these binding events are coupled with transduction processes that begin to change when they are exposed to the messy world of real samples. With the advent of fundamental breakthroughs at the intersection of materials science, micro- and nano-technology, and signal processing, hybrid chemo-sensory systems have incorporated tunable, optimizable operating parameters, through which changes in the response characteristics can be modeled and compensated as the environmental conditions or application needs change. The objective of this article, in this context, is to bring together the key advances at the device, data processing, and system levels that enable chemo-sensory systems to "adapt" in response to their environments. Accordingly, in this review we will feature the research effort made by selected experts on chemical sensing and information theory, whose work has been devoted to develop strategies that provide tunability and adaptability to single sensor devices or sensory array systems. Particularly, we consider sensor-array selection, modulation of internal sensing parameters, and active sensing. The article ends with some conclusions drawn from the results presented and a visionary look toward the future in terms of how the field may evolve. PMID- 22319493 TI - Mobile robots for localizing gas emission sources on landfill sites: is bio inspiration the way to go? AB - Roboticists often take inspiration from animals for designing sensors, actuators, or algorithms that control the behavior of robots. Bio-inspiration is motivated with the uncanny ability of animals to solve complex tasks like recognizing and manipulating objects, walking on uneven terrains, or navigating to the source of an odor plume. In particular the task of tracking an odor plume up to its source has nearly exclusively been addressed using biologically inspired algorithms and robots have been developed, for example, to mimic the behavior of moths, dung beetles, or lobsters. In this paper we argue that biomimetic approaches to gas source localization are of limited use, primarily because animals differ fundamentally in their sensing and actuation capabilities from state-of-the-art gas-sensitive mobile robots. To support our claim, we compare actuation and chemical sensing available to mobile robots to the corresponding capabilities of moths. We further characterize airflow and chemosensor measurements obtained with three different robot platforms (two wheeled robots and one flying micro-drone) in four prototypical environments and show that the assumption of a constant and unidirectional airflow, which is the basis of many gas source localization approaches, is usually far from being valid. This analysis should help to identify how underlying principles, which govern the gas source tracking behavior of animals, can be usefully "translated" into gas source localization approaches that fully take into account the capabilities of mobile robots. We also describe the requirements for a reference application, monitoring of gas emissions at landfill sites with mobile robots, and discuss an engineered gas source localization approach based on statistics as an alternative to biologically inspired algorithms. PMID- 22319494 TI - Changes in Physiology before, during, and after Yawning. AB - The ultimate function of yawning continues to be debated. Here, we examine physiological measurements taken before, during, and after yawns in humans, in an attempt to identify key proximate mechanisms associated with this behavior. In two separate studies we measured changes in heart rate, lung volume, eye closure, skin conductance, ear pulse, respiratory sinus arrhythmia, and respiratory rate. Data were depicted from 75 s before and after yawns, and analyzed at baseline, during, and immediately following yawns. Increases in heart rate, lung volume, and eye muscle tension were observed during or immediately following yawning. Patterns of physiological changes during yawning were then compared to data from non-yawning deep inhalations. In one study, respiration period increased following the execution of a yawn. Much of the variance in physiology surrounding yawning was specific to the yawning event. This was not the case for deep inhalation. We consider our findings in light of various hypotheses about the function of yawning and conclude that they are most consistent with the brain cooling hypothesis. PMID- 22319495 TI - Continuity, divergence, and the evolution of brain language pathways. AB - Recently, the assumption of evolutionary continuity between humans and non-human primates has been used to bolster the hypothesis that human language is mediated especially by the ventral extreme capsule pathway that mediates auditory object recognition in macaques. Here, we argue for the importance of evolutionary divergence in understanding brain language evolution. We present new comparative data reinforcing our previous conclusion that the dorsal arcuate fasciculus pathway was more significantly modified than the ventral extreme capsule pathway in human evolution. Twenty-six adult human and twenty-six adult chimpanzees were imaged with diffusion-weighted MRI and probabilistic tractography was used to track and compare the dorsal and ventral language pathways. Based on these and other data, we argue that the arcuate fasciculus is likely to be the pathway most essential for higher-order aspects of human language such as syntax and lexical semantics. PMID- 22319496 TI - Mental state attribution and body configuration in women. AB - Body configuration is a sexually dimorphic trait. In humans, men tend to have high shoulder-to-hip ratios. Women in contrast, often have low waist-to-hip ratios (WHR); i.e., narrow waists and broad hips that approximate an hour-glass configuration. Women with low WHR's are rated as more attractive, healthier, and more fertile. They also tend to have more attractive voices, lose their virginity sooner, and have more sex partners. WHR has also been linked with general cognitive performance. In the present study we expand upon previous research examining the role of WHR in cognition. We hypothesized that more feminine body types, as indexed by a low WHR, would be associated with cognitive measures of the female "brain type," such as mental state attribution and empathy because both may depend upon the activational effects of estrogens at puberty. We found that women with low WHRs excel at identifying emotional states of other people and show a cognitive style that favors empathizing over systemizing. We suggest this relationship may be a byproduct of greater gluteofemoral fat stores which are high in the essential fatty acids needed to support brain development and cellular functioning. It is interesting to note that our findings suggest lower WHR females, who are more likely to be targeted for dishonest courtship, may be better at identifying disingenuous claims of commitment. PMID- 22319497 TI - Sirtuins and disease: the road ahead. AB - Sirtuins represent a promising new class of conserved histone deacetylases, originally identified in yeast. The activity of the sirtuin (SirT) family - made up of seven members (SirT1-7) - is NAD(+) dependent. Sirtuins target a wide range of cellular proteins in nucleus, cytoplasm, and mitochondria for post translational modification by acetylation (SirT1, 2, 3, and 5) or ADP ribosylation (SirT4 and 6). Sirtuins regulate responses to stress and ensure that damaged DNA is not propagated, thus contrasting the accumulation of mutations. To date, sirtuins have emerged as potential therapeutic targets for treatment of human pathologies such as metabolic, cardiovascular and neurodegenerative diseases, and cancer. SirT1 is the founding member of this class of enzymes and is currently the best known of the group. SirT1 acts in various cellular processes, deacetylating both chromatin and non-histone proteins, and its role in cancer and aging has been extensively studied. SirT1 may play a critical role in tumor initiation and progression as well as drug resistance by blocking senescence and apoptosis, and by promoting cell growth and angiogenesis. Recently, growing interest in sirtuin modulation has led to the discovery and characterization of small molecules able to modify sirtuin activity. The present review highlights SirT mechanism(s) of action and deregulation in cancer, focusing on the therapeutic potential of SirT modulators both in cancer prevention and treatment. PMID- 22319498 TI - Aldo-Keto Reductase 1B10 and Its Role in Proliferation Capacity of Drug-Resistant Cancers. AB - The human aldo-keto reductase AKR1B10, originally identified as an aldose reductase-like protein and human small intestine aldose reductase, is a cytosolic NADPH-dependent reductase that metabolizes a variety of endogenous compounds, such as aromatic and aliphatic aldehydes and dicarbonyl compounds, and some drug ketones. The enzyme is highly expressed in solid tumors of several tissues including lung and liver, and as such has received considerable interest as a relevant biomarker for the development of those tumors. In addition, AKR1B10 has been recently reported to be significantly up-regulated in some cancer cell lines (medulloblastoma D341 and colon cancer HT29) acquiring resistance toward chemotherapeutic agents (cyclophosphamide and mitomycin c), suggesting the validity of the enzyme as a chemoresistance marker. Although the detailed information on the AKR1B10-mediated mechanisms leading to the drug resistance process is not well understood so far, the enzyme has been proposed to be involved in functional regulations of cell proliferation and metabolism of drugs and endogenous lipids during the development of chemoresistance. This article reviews the current literature focusing mainly on expression profile and roles of AKR1B10 in the drug resistance of cancer cells. Recent developments of AKR1B10 inhibitors and their usefulness in restoring sensitivity to anticancer drugs are also reviewed. PMID- 22319499 TI - Gene Cloning and mRNA Expression of Glutamate Dehydrogenase in the Liver, Brain, and Intestine of the Swamp Eel, Monopterus albus (Zuiew), Exposed to Freshwater, Terrestrial Conditions, Environmental Ammonia, or Salinity Stress. AB - The swamp eel, Monopterus albus, is an obligatory air-breathing teleost which can undergo long period of emersion, has high environmental and tissue ammonia tolerance, and can survive in brackish water. We obtained a cDNA sequence of glutamate dehydrogenase (gdh), which consisted of a 133-bp 5' UTR, a complete coding sequence region spanning 1629 bp and a 3' UTR of approximately 717 bp, from the liver, intestine, and brain of M. albus. The translated Gdh amino acid sequence had 542 residues, and it formed a monophyletic clade with Bostrychus sinensis Gdh1a, Tetraodon nigroviridis Gdh1a, Chaenocephalus aceratus Gdh1a, Salmo salar Gdh1a1 and Gdh1a2, and O. mykiss Gdh1a. One day of exposure to terrestrial conditions or 75 mmol l(-1) NH(4)Cl, but not to water at salinity 20, resulted in a significant increase in mRNA expression of gdh1a and Gdh amination activity in the liver of M. albus. However, exposure to brackish water, but not to terrestrial conditions or 75 mmol l(-1) NH(4)Cl, led to a significant increase in the mRNA expression of gdh1a and Gdh amination activity in the intestine. By contrast, all the three experimental conditions had no significant effects on the mRNA expression of gdh1a in the brain of M. albus, despite a significant decrease in the Gdh amination activity in the brain of fish exposed to 75 mmol l(-1) NH(4)Cl for 6 days. Our results indicate for the first time that the mRNA expression of gdh1a was differentially up-regulated in the liver and intestine of M. albus in response to ammonia toxicity and salinity stress, respectively. The increases in mRNA expression of gdh1a and Gdh amination activity would probably lead to an increase in glutamate production in support of increased glutamine synthesis for the purpose of ammonia detoxification or cell volume regulation under these two different environmental conditions. PMID- 22319500 TI - The recognition of chaos in host-pathogen response. PMID- 22319501 TI - The dreaming brain/mind: a role in understanding complex mental disorders? PMID- 22319502 TI - Nature or nurture in finger counting: a review on the determinants of the direction of number-finger mapping. AB - The spontaneous use of finger counting has been for long recognized as critical to the acquisition of number skills. Recently, the great interest on space-number associations shifted attention to the practice of finger counting itself, and specifically, to its spatial components. Besides general cross-cultural differences in mapping numbers onto fingers, contrasting results have been reported with regard to the directional features of this mapping. The key issue we address is to what extent directionality is culturally mediated, i.e., linked to the conventional reading-writing system direction, and/or biologically determined, i.e., linked to hand dominance. Although the preferred starting-hand for counting seems to depend on the surveyed population, even within the same population high inter-individual variability minimizes the role of cultural factors. Even if so far largely overlooked, handedness represents a sound candidate for shaping finger counting direction. Here we discuss adults and developmental evidence in support of this view and we reconsider the plausibility of multiple and coexistent number-space mapping in physical and representational space. PMID- 22319503 TI - The nature of belief-directed exploratory choice in human decision-making. AB - In non-stationary environments, there is a conflict between exploiting currently favored options and gaining information by exploring lesser-known options that in the past have proven less rewarding. Optimal decision-making in such tasks requires considering future states of the environment (i.e., planning) and properly updating beliefs about the state of the environment after observing outcomes associated with choices. Optimal belief-updating is reflective in that beliefs can change without directly observing environmental change. For example, after 10 s elapse, one might correctly believe that a traffic light last observed to be red is now more likely to be green. To understand human decision-making when rewards associated with choice options change over time, we develop a variant of the classic "bandit" task that is both rich enough to encompass relevant phenomena and sufficiently tractable to allow for ideal actor analysis of sequential choice behavior. We evaluate whether people update beliefs about the state of environment in a reflexive (i.e., only in response to observed changes in reward structure) or reflective manner. In contrast to purely "random" accounts of exploratory behavior, model-based analyses of the subjects' choices and latencies indicate that people are reflective belief updaters. However, unlike the Ideal Actor model, our analyses indicate that people's choice behavior does not reflect consideration of future environmental states. Thus, although people update beliefs in a reflective manner consistent with the Ideal Actor, they do not engage in optimal long-term planning, but instead myopically choose the option on every trial that is believed to have the highest immediate payoff. PMID- 22319504 TI - Selectivity of face distortion aftereffects for differences in expression or gender. AB - The perceived configuration of a face can be strongly biased by prior adaptation to a face with a distorted configuration. These aftereffects have been found to be weaker when the adapt and test faces differ along a number of dimensions. We asked whether the adaptation shows more transfer between faces that share a common identity, by comparing the strength of aftereffects when the adapt and test faces differed either in expression (a configural change in the same face identity) or gender (a configural change between identities). Observers adapted to expanded or contracted images of either male or female faces with either happy or fearful expressions, and then judged the perceived configuration in either the same faces or faces with a different gender and/or expression. The adaptation included exposure to a single face (e.g., expanded happy) or to alternated faces where the distortion was contingent on the attribute (e.g., expanded happy versus contracted fearful). In all cases the aftereffects showed strong transfer and thus only weak selectivity. However, selectivity was equal or stronger for the change in expression than gender. Our results thus suggest that the distortion aftereffects between faces can be weakly modulated by both variant and invariant attributes of the face. PMID- 22319505 TI - Surgical management of cavernous malformations presenting with drug-resistant epilepsy. AB - Cerebral cavernous malformations (CMs) are dynamic lesions characterized by continuous size changes and repeated bleeding. When involving cortical tissue, CMs pose a significant risk for the development of drug-resistant epilepsy, which is thought to be result of an altered neuronal network caused by the lesion itself and its blood degradation products. Preoperative evaluation should comprise a complete seizure history, neurological examination, epilepsy-oriented MRI, EEG, video-EEG, completed with SPECT, PET, functional MRI, and/or invasive monitoring as needed. Radiosurgery shows variable rates of seizure freedom and a high incidence of complications, thus microsurgical resection remains the optimal treatment for CMs presenting with drug-resistant epilepsy. Two thirds of patients reach Engel I class at 3-year follow-up, regardless of lobar location. Those with secondarily generalized seizures, a higher seizure frequency, and generalized abnormalities on preoperative or postoperative EEG, show poorer outcomes, while factors such as gender, duration of epilepsy, lesion size, age, bleeding at the time of surgery, do not correlate consistently with seizure outcome. Electrocorticography and a meticulous removal of all cortical hemosiderin - beyond pure lesionectomy - reduce the risk of symptomatic recurrences. PMID- 22319506 TI - The effect of pupil size on stimulation of the melanopsin containing retinal ganglion cells, as evaluated by monochromatic pupillometry. AB - PURPOSE: To evaluate the influence of the size of the light exposed pupil in one eye on the pupillary light reflex of the other eye. METHOD: Using a monochromatic pupillometer, the left eye in each of 10 healthy subjects was exposed to 20 s of monochromatic light of luminance 300 cd/m(2), first red (660 nm) and in a following session, blue (470 nm) light. The consensual pupillary diameter in the right eye was continuously measured before, during, and after light exposure. Subsequently, Tropicamide 1% or Pilocarpine 2% was instilled into the left eye and when the pupil was either maximally dilated or contracted, the entire sequence of red and blue light exposure repeated. After at least 3 days, when the effect of the eye drop had subsided, the entire experiment was repeated, this time employing the other substance. RESULTS: Prior dilatation of the left pupil augmented the post light contraction to blue (p < 0.0001), but not to red light. The contraction during light exposure did not change. Prior contraction of the left pupil decreased the post-stimulus contraction to blue light (p < 0.04). CONCLUSION: The size of the light exposed pupil influences the magnitude of the response to blue, but not to red light. Prior dilatation may therefore prove useful, when the response to blue light - as a marker of melanopsin containing retinal ganglion cell function - is of interest, especially when this response is weak. PMID- 22319507 TI - Association of skin with the pathogenesis and treatment of neurodegenerative amyloidosis. AB - Amyloidosis are a large group of conformational diseases characterized by abnormal protein folding and assembly which results in the accumulation of insoluble protein aggregates that may accumulate systemically or locally in certain organs or tissue. In local amyloidosis, amyloid deposits are restricted to a particular organ or tissue. Alzheimer's, Parkinson's disease, and amyotrophic lateral sclerosis are some examples of neurodegenerative amyloidosis. Local manifestation of protein aggregation in the skin has also been reported. Brain and skin are highly connected at a physiological and pathological level. Recently several studies demonstrated a strong connection between brain and skin in different amyloid diseases. In the present review, we discuss the relevance of the "brain-skin connection" in different neurodegenerative amyloidosis, not only at the pathological level, but also as a strategy for the treatment of these diseases. PMID- 22319508 TI - Gamma band activity in the reticular activating system. AB - This review considers recent evidence showing that cells in three regions of the reticular activating system (RAS) exhibit gamma band activity, and describes the mechanisms behind such manifestation. Specifically, we discuss how cells in the mesopontine pedunculopontine nucleus (PPN), intralaminar parafascicular nucleus (Pf), and pontine subcoeruleus nucleus dorsalis (SubCD) all fire in the beta/gamma band range when maximally activated, but no higher. The mechanisms behind this ceiling effect have been recently elucidated. We describe recent findings showing that every cell in the PPN have high-threshold, voltage dependent P/Q-type calcium channels that are essential, while N-type calcium channels are permissive, to gamma band activity. Every cell in the Pf also showed that P/Q-type and N-type calcium channels are responsible for this activity. On the other hand, every SubCD cell exhibited sodium-dependent subthreshold oscillations. A novel mechanism for sleep-wake control based on well-known transmitter interactions, electrical coupling, and gamma band activity is described. The data presented here on inherent gamma band activity demonstrates the global nature of sleep-wake oscillation that is orchestrated by brainstem thalamic mechanism, and questions the undue importance given to the hypothalamus for regulation of sleep-wakefulness. The discovery of gamma band activity in the RAS follows recent reports of such activity in other subcortical regions like the hippocampus and cerebellum. We hypothesize that, rather than participating in the temporal binding of sensory events as seen in the cortex, gamma band activity manifested in the RAS may help stabilize coherence related to arousal, providing a stable activation state during waking and paradoxical sleep. Most of our thoughts and actions are driven by pre-conscious processes. We speculate that continuous sensory input will induce gamma band activity in the RAS that could participate in the processes of pre-conscious awareness, and provide the essential stream of information for the formulation of many of our actions. PMID- 22319510 TI - Long-Term Persistent GBV-B Infection and Development of a Chronic and Progressive Hepatitis C-Like Disease in Marmosets. AB - It has been shown that infection of GB virus B (GBV-B), which is closely related to hepatitis C virus, develops acute self-resolving hepatitis in tamarins. In this study we sought to examine longitudinally the dynamics of viral and immunological status following GBV-B infection of marmosets and tamarins. Surprisingly, two of four marmosets but not tamarins experimentally challenged with GBV-B developed long-term chronic infection with fluctuated viremia, recurrent increase of alanine aminotransferase and plateaued titers of the antiviral antibodies, which was comparable to chronic hepatitis C in humans. Moreover, one of the chronically infected marmosets developed an acute exacerbation of chronic hepatitis as revealed by biochemical, histological, and immunopathological analyses. Of note, periodical analyses of the viral genomes in these marmosets indicated frequent and selective non-synonymous mutations, suggesting efficient evasion of the virus from antiviral immune pressure. These results demonstrated for the first time that GBV-B could induce chronic hepatitis C-like disease in marmosets and that the outcome of the viral infection and disease progression may depend on the differences between species and individuals. PMID- 22319511 TI - Measles virus hemagglutinin: structural insights into cell entry and measles vaccine. AB - Measles is one of the most contagious viral diseases, and remains a major cause of childhood morbidity and mortality worldwide. The measles virus (MV), a member of the family Paramyxoviridae, enters cells through a cellular receptor, the signaling lymphocyte activation molecule (SLAM), CD46 or nectin-4. Entry is mediated by two MV envelope glycoproteins, the hemagglutinin (H) and the fusion (F) protein. The H protein mediates receptor attachment, while the F protein causes membrane fusion. The interaction between the H and F proteins is essential to initiate the cell entry process. Recently determined crystal structures of the MV-H protein unbound and bound to SLAM or CD46 have provided insights into paramyxovirus entry and the effectiveness of measles vaccine. PMID- 22319509 TI - Sympathetic and catecholaminergic alterations in sleep apnea with particular emphasis on children. AB - Sleep is involved in the regulation of major organ functions in the human body, and disruption of sleep potentially can elicit organ dysfunction. Obstructive sleep apnea (OSA) is the most prevalent sleep disorder of breathing in adults and children, and its manifestations reflect the interactions between intermittent hypoxia, intermittent hypercapnia, increased intra-thoracic pressure swings, and sleep fragmentation, as elicited by the episodic changes in upper airway resistance during sleep. The sympathetic nervous system is an important modulator of the cardiovascular, immune, endocrine and metabolic systems, and alterations in autonomic activity may lead to metabolic imbalance and organ dysfunction. Here we review how OSA and its constitutive components can lead to perturbation of the autonomic nervous system in general, and to altered regulation of catecholamines, both of which then playing an important role in some of the mechanisms underlying OSA-induced morbidities. PMID- 22319512 TI - Role of Shrimp Chitin in the Ecology of Toxigenic Vibrio cholerae and Cholera Transmission. AB - Seasonal plankton blooms correlate with occurrence of cholera in Bangladesh, although the mechanism of how dormant Vibrio cholerae, enduring interepidemic period in biofilms and plankton, initiates seasonal cholera is not fully understood. In this study, laboratory microcosms prepared with estuarine Mathbaria water (MW) samples supported active growth of toxigenic V. cholerae O1 up to 7 weeks as opposed to 6 months when microcosms were supplemented with dehydrated shrimp chitin chips (CC) as the single source of nutrient. Bacterial counting and detection of wbe and ctxA genes were done employing culture, direct fluorescent antibody (DFA) assay, and multiplex-polymerase chain reaction methods. In MW microcosm, the aqueous phase became clear as the non-culturable cells settled, whereas the aqueous phase of the MW-CC microcosm became turbid from bacterial growth stimulated by chitin. Bacterial chitin degradation and biofilm formation proceeded from an initial steady state to a gradually declining bacterial culturable count. V. cholerae within the microenvironments of chitin and chitin-associated biofilms remained metabolically active even in a high acidic environment without losing either viability or virulence. It is concluded that the abundance of chitin that occurs during blooms plays an important role in the aquatic life cycle of V. cholerae and, ultimately, in the seasonal transmission of cholera. PMID- 22319513 TI - Bottlenecks in the transferability of antibiotic resistance from natural ecosystems to human bacterial pathogens. AB - It is generally accepted that resistance genes acquired by human pathogens through horizontal gene transfer originated in environmental, non-pathogenic bacteria. As a consequence, there is increasing concern on the roles that natural, non-clinical ecosystems, may play in the evolution of resistance. Recent studies have shown that the variability of determinants that can provide antibiotic resistance on their expression in a heterologous host is much larger than what is actually found in human pathogens, which implies the existence of bottlenecks modulating the transfer, spread, and stability of antibiotic resistance genes. In this review, the role that different factors such as founder effects, ecological connectivity, fitness costs, or second-order selection may have on the establishment of a specific resistance determinant in a population of bacterial pathogens is analyzed. PMID- 22319514 TI - CTL Escape and Viral Fitness in HIV/SIV Infection. AB - Cytotoxic T lymphocyte (CTL) responses exert a suppressive effect on HIV and simian immunodeficiency virus (SIV) replication. Under the CTL pressure, viral CTL escape mutations are frequently selected with viral fitness costs. Viruses with such CTL escape mutations often need additional viral genome mutations for recovery of viral fitness. Persistent HIV/SIV infection sometimes shows replacement of a CTL escape mutation with an alternative escape mutation toward higher viral fitness. Thus, multiple viral genome changes under CTL pressure are observed in the chronic phase of HIV/SIV infection. HIV/SIV transmission to HLA/MHC-mismatched hosts drives further viral genome changes including additional CTL escape mutations and reversions under different CTL pressure. Understanding of viral structure/function and host CTL responses would contribute to prediction of HIV evolution and control of HIV prevalence. PMID- 22319515 TI - Prospects for the study of evolution in the deep biosphere. AB - Since the days of Darwin, scientists have used the framework of the theory of evolution to explore the interconnectedness of life on Earth and adaptation of organisms to the ever-changing environment. The advent of molecular biology has advanced and accelerated the study of evolution by allowing direct examination of the genetic material that ultimately determines the phenotypes upon which selection acts. The study of evolution has been furthered through examination of microbial evolution, with large population numbers, short generation times, and easily extractable DNA. Such work has spawned the study of microbial biogeography, with the realization that concepts developed in population genetics may be applicable to microbial genomes (Martiny et al., 2006; Manhes and Velicer, 2011). Microbial biogeography and adaptation has been examined in many different environments. Here we argue that the deep biosphere is a unique environment for the study of evolution and list specific factors that can be considered and where the studies may be performed. This publication is the result of the NSF-funded Center for Dark Energy Biosphere Investigations (C-DEBI) theme team on Evolution (www.darkenergybiosphere.org). PMID- 22319516 TI - Kaposi's Sarcoma Associated Herpesvirus Entry into Target Cells. AB - Herpesvirus infection of target cells is a complex process involving multiple host cell surface molecules (receptors) and multiple viral envelope glycoproteins. Kaposi's sarcoma associated herpesvirus (KSHV or HHV-8) infects a variety of in vivo target cells such as endothelial cells, B cells, monocytes, epithelial cells, and keratinocytes. KSHV also infects a diversity of in vitro target cells and establishes in vitro latency in many of these cell types. KSHV interactions with the host cell surface molecules and its mode of entry in the various target cells are critical for the understanding of KSHV pathogenesis. KSHV is the first herpesvirus shown to interact with adherent target cell integrins and this interaction initiates the host cell pre-existing signal pathways that are utilized for successful infection. This chapter discusses the various aspects of the early stage of KSHV infection of target cells, receptors used and issues that need to be clarified, and future directions. The various signaling events triggered by KSHV infection and the potential role of signaling events in the different stages of infection are summarized providing the framework and starting point for further detailed studies essential to fully comprehend the pathogenesis of KSHV. PMID- 22319517 TI - Inhibition of bacterial ammonia oxidation by organohydrazines in soil microcosms. AB - Hydroxylamine oxidation by hydroxylamine oxidoreductase (HAO) is a key step for energy-yielding in support of the growth of ammonia-oxidizing bacteria (AOB). Organohydrazines have been shown to inactivate HAO from Nitrosomonas europaea, and may serve as selective inhibitors to differentiate bacterial from archaeal ammonia oxidation due to the absence of bacterial HAO gene homolog in known ammonia-oxidizing archaea (AOA). In this study, the effects of three organohydrazines on activity, abundance, and composition of AOB and AOA were evaluated in soil microcosms. The results indicate that phenylhydrazine and methylhydrazine at the concentration of 100 MUmol g(-1) dry weight soil completely suppressed the activity of soil nitrification. Denaturing gradient gel electrophoresis fingerprinting and sequencing analysis of bacterial ammonia monooxygenase subunit A gene (amoA) clearly demonstrated that nitrification activity change is well paralleled with the growth of Nitrosomonas europaea-like AOB in soil microcosms. No significant correlation between AOA community structure and nitrification activity was observed among all treatments during the incubation period, although incomplete inhibition of nitrification activity occurred in 2-hydroxyethylhydrazine-amended soil microcosms. These findings show that the HAO-targeted organohydrazines can effectively inhibit bacterial nitrification in soil, and the mechanism of organohydrazine affecting AOA remains unclear. PMID- 22319518 TI - Quantification of Microbial Communities in Subsurface Marine Sediments of the Black Sea and off Namibia. AB - Organic-rich subsurface marine sediments were taken by gravity coring up to a depth of 10 m below seafloor at six stations from the anoxic Black Sea and the Benguela upwelling system off Namibia during the research cruises Meteor 72-5 and 76-1, respectively. The quantitative microbial community composition at various sediment depths was analyzed using total cell counting, catalyzed reporter deposition - fluorescence in situ hybridization (CARD-FISH) and quantitative real time PCR (Q-PCR). Total cell counts decreased with depths from 10(9) to 10(10) cells/mL at the sediment surface to 10(7)-10(9) cells/mL below one meter depth. Based on CARD-FISH and Q-PCR analyses overall similar proportions of Bacteria and Archaea were found. The down-core distribution of prokaryotic and eukaryotic small subunit ribosomal RNA genes (16S and 18S rRNA) as well as functional genes involved in different biogeochemical processes was quantified using Q-PCR. Crenarchaeota and the bacterial candidate division JS-1 as well as the classes Anaerolineae and Caldilineae of the phylum Chloroflexi were highly abundant. Less abundant but detectable in most of the samples were Eukarya as well as the metal and sulfate-reducing Geobacteraceae (only in the Benguela upwelling influenced sediments). The functional genes cbbL, encoding for the large subunit of RuBisCO, the genes dsrA and aprA, indicative of sulfate-reducers as well as the mcrA gene of methanogens were detected in the Benguela upwelling and Black Sea sediments. Overall, the high organic carbon content of the sediments goes along with high cell counts and high gene copy numbers, as well as an equal abundance of Bacteria and Archaea. PMID- 22319519 TI - Novel Degenerate PCR Method for Whole-Genome Amplification Applied to Peru Margin (ODP Leg 201) Subsurface Samples. AB - A degenerate polymerase chain reaction (PCR)-based method of whole-genome amplification, designed to work fluidly with 454 sequencing technology, was developed and tested for use on deep marine subsurface DNA samples. While optimized here for use with Roche 454 technology, the general framework presented may be applicable to other next generation sequencing systems as well (e.g., Illumina, Ion Torrent). The method, which we have called random amplification metagenomic PCR (RAMP), involves the use of specific primers from Roche 454 amplicon sequencing, modified by the addition of a degenerate region at the 3' end. It utilizes a PCR reaction, which resulted in no amplification from blanks, even after 50 cycles of PCR. After efforts to optimize experimental conditions, the method was tested with DNA extracted from cultured E. coli cells, and genome coverage was estimated after sequencing on three different occasions. Coverage did not vary greatly with the different experimental conditions tested, and was around 62% with a sequencing effort equivalent to a theoretical genome coverage of 14.10*. The GC content of the sequenced amplification product was within 2% of the predicted values for this strain of E. coli. The method was also applied to DNA extracted from marine subsurface samples from ODP Leg 201 site 1229 (Peru Margin), and results of a taxonomic analysis revealed microbial communities dominated by Proteobacteria, Chloroflexi, Firmicutes, Euryarchaeota, and Crenarchaeota, among others. These results were similar to those obtained previously for those samples; however, variations in the proportions of taxa identified illustrates well the generally accepted view that community analysis is sensitive to both the amplification technique used and the method of assigning sequences to taxonomic groups. Overall, we find that RAMP represents a valid methodology for amplifying metagenomes from low-biomass samples. PMID- 22319520 TI - There Must be an Acetogen Somewhere. PMID- 22319521 TI - An angiotensin II type 1 receptor blocker prevents renal injury via inhibition of the Notch pathway in Ins2 Akita diabetic mice. AB - Recently, it has been reported that the Notch pathway is involved in the pathogenesis of diabetic nephropathy. In this study, we investigated the activation of the Notch pathway in Ins2 Akita diabetic mouse (Akita mouse) and the effects of telmisartan, an angiotensin II type1 receptor blocker, on the Notch pathway. The intracellular domain of Notch1 (ICN1) is proteolytically cleaved from the cell plasma membrane in the course of Notch activation. The expression of ICN1 and its ligand, Jagged1, were increased in the glomeruli of Akita mice, especially in the podocytes. Administration of telmisartan significantly ameliorated the expression of ICN1 and Jagged1. Telmisartan inhibited the angiotensin II-induced increased expression of transforming growth factor beta and vascular endothelial growth factor A which could directly activate the Notch signaling pathway in cultured podocytes. Our results indicate that the telmisartan prevents diabetic nephropathy through the inhibition of the Notch pathway. PMID- 22319522 TI - Pentoxifylline attenuates methionine- and choline-deficient-diet-induced steatohepatitis by suppressing TNF-alpha expression and endoplasmic reticulum stress. AB - BACKGROUND: Pentoxifylline (PTX) anti-TNF properties are known to exert hepatoprotective effects in various liver injury models. The aim of this study was to investigate whether PTX has beneficial roles in the development of methionine- and choline-deficient-(MCD-) diet-induced NAFLD SD rats in vivo and TNF-alpha-induced Hep3B cells in vitro. METHODS: SD Rats were classified according to diet (chow or MCD diet) and treatment (normal saline or PTX injection) over a period of 4 weeks: group I (chow + saline, n = 4), group II (chow + PTX), group III (MCD + saline), and group IV (MCD + PTX). Hep3B cells were treated with 100 ng/ml TNF-alpha (24 h) in the absence or presence of PTX (1 mM). RESULTS: PTX attenuated MCD-diet-induced serum ALT levels and hepatic steatosis. In real-time PCR and western blotting analysis, PTX decreased MCD-diet induced TNF-alpha mRNA expression and proapoptotic unfolded protein response by ER stress (GRP78, p-eIF2, ATF4, IRE1alpha, CHOP, and p-JNK activation) in vivo. PTX (1 mM) reduced TNF-alpha-induced activation of GRP78, p-eIF2, ATF4, IRE1alpha, and CHOP in vitro. CONCLUSION: PTX has beneficial roles in the development of MCD-diet-induced steatohepatitis through partial suppression of TNF-alpha and ER stress. PMID- 22319523 TI - Frequency of Thyroid Nodules among Patients with Colonic Polyps. AB - Aim. Colonic polyps and thyroid nodules are common diseases and their frequency increases with age. In the literature, there is no study investigating the coexistence of colonic polyps and thyroid nodules. Therefore, this study was designed to investigate thyroid nodule prevalence in patients with colonic polyps. Material and Methods. Sixty-six patients with colonic polyps and 146 patients without colonic polyps enrolled into the study. Age and sex matched control group was composed from patients without colonic polyps. Colonoscopic examinations, thyroid ultrasonographies were performed in all patients, and TSH were measured. Results. Male/female ratio in polyp and control groups were 40/26 versus 68/78, respectively (P = 0.058). Mean ages were similar in both groups (53.3 +/- 11.4 versus, 51.8 +/- 11.4, P = 0.373). Thyroid nodule was detected in 44 (66.7%) patients with polyps and in 61 (41.8%) controls (P = 0.001). Patients with adenomatous polyps had 5 or more thyroid nodules compared to patients with hyperplastic polyps (P = 0.03). Thyroid nodules were more prevalent among patients aged 50 or older compared to 50 years or less (P = 0.023). Conclusion. Thyroid nodules were detected more common in patients with colonic polyps. Further studies are needed to clarify this coexistence. PMID- 22319524 TI - Confocal endomicroscopy of colorectal polyps. AB - Confocal laser endomicroscopy (CLE) is one of several novel methods that provide real-time, high-resolution imaging at a micron scale via endoscopes. CLE has the potential to be a disruptive technology in that it can change the current algorithms that depend on biopsy to perform surveillance of high-risk conditions. Furthermore, it allows on-table decision making that has the potential to guide therapy in real time and reduce the need for repeated procedures. CLE and related technologies are often termed "virtual biopsy" as they simulate the images seen in traditional histology. However, the imaging of living tissue allows more than just pragmatic convenience; it also allows imaging of living tissue such as active capillary circulation, cellular death, and vascular and endothelial translocation, thus extending beyond what is capable in traditional biopsy. Immediate potential applications of CLE are to guide biopsy sampling in Barrett's esophagus and inflammatory bowel disease surveillance, evaluation of colorectal polyps, and intraductal imaging of the pancreas and bile duct. Data on these applications is rapidly emerging, and more is needed to clearly demonstrate the optimal applications of CLE. In this paper, we will focus on the role of CLE as applied to colorectal polyps detected during colonoscopy. PMID- 22319525 TI - Effect of a CNS-Sensitive Anticholinesterase Methane Sulfonyl Fluoride on Hippocampal Acetylcholine Release in Freely Moving Rats. AB - Anticholinesterases (antiChEs) are used to treat Alzheimer's disease. The comparative effects of two antiChEs, methanesulfonyl fluoride (MSF) and donepezil, on the extracellular levels of ACh in the hippocampus were investigated by in vivo microdialysis in freely moving rats. MSF at 1 and 2 mg/kg produced a dose-dependent increase in ACh efflux from 10 min to at least 3 hrs after injection. At 2 mg/kg, the increase was still present at 24 hr. Donepezil at 1 mg/kg showed a similar but smaller effect, and, paradoxically, 2 mg/kg showed no consistent effect. MSF at 1 and 2 mg/kg decreased acetylcholinesterase activity in the hippocampus to 54.8 and 20.1% of control, respectively. These results suggest that MSF is a suitable candidate for the treatment of Alzheimer's disease. PMID- 22319526 TI - Molecular bases and phenotypic determinants of aromatase excess syndrome. AB - Aromatase excess syndrome (AEXS) is a rare autosomal dominant disorder characterized by gynecomastia. This condition is caused by overexpression of CYP19A1 encoding aromatase, and three types of cryptic genomic rearrangement around CYP19A1, that is, duplications, deletions, and inversions, have been identified in AEXS. Duplications appear to have caused CYP19A1 overexpression because of an increased number of physiological promoters, whereas deletions and inversions would have induced wide CYP19A1 expression due to the formation of chimeric genes consisting of a noncoding exon(s) of a neighboring gene and CYP19A1 coding exons. Genotype-phenotype analysis implies that phenotypic severity of AEXS is primarily determined by the expression pattern of CYP19A1 and the chimeric genes and by the structural property of the fused exons with a promoter function (i.e., the presence or the absence of a natural translation start codon). These results provide novel information about molecular mechanisms of human genetic disorders and biological function of estrogens. PMID- 22319527 TI - Male fertility and reduction in semen parameters: a single tertiary-care center experience. AB - Background. Infertility is both a clinical and a public problem, affecting the life of the couple, the healthcare services, and social environment. Standard semen analysis is the surrogate measure of male fertility in clinical practice. Objective. To provide information about the relationship between semen parameters and spontaneous conception. Methods. We evaluated retrospectively 453 pregnancies that occurred among 2935 infertile couples evaluated at an infertility clinic of a tertiary-care university hospital, between 2004 and 2009. Results. Normal semen analysis was present only in 158 patients; 295 subfertile patients showed alterations in at least one seminal parameter. A reduction in all seminal parameters was observed in 41 patients. Etiological causes of male infertility were identified in 314 patients. Conclusion. Our data highlights the possibility of a spontaneous conception with semen parameters below WHO reference values. Therefore, we support the importance of defining reference values on a population of fertile men. Finally, we analyzed the related ethical issues. PMID- 22319528 TI - Further evidence on the role of thyroid autoimmunity in women with recurrent miscarriage. AB - It has been twenty years since the first paper reporting the association between thyroid antibodies (TAIs) and spontaneous miscarriage was published. Following this observation, several studies have clearly demonstrated an increased prevalence of TAI in patients with recurrent miscarriage (RM). However, the exact mechanism underlying this association remains a matter of debate. The aim of the present study was to evaluate the thyroid function, throughout a specific test, in patient with RM and TAI focusing on the hypothesis that TAI should be an indirect sign of a mild thyroid dysfunction. 46 patients with RM and TAI were included in the study. All patients underwent short TRH stimulation test showing an abnormal response in the vast majority of cases (65%). Normal FT4 and FT3 mean values were found whereas TSH values were in the upper normal range (2.64 +/- 1.3 mUI/L). Our data support the hypothesis that in patients with RM the presence of TAI is an indirect sign of a subtle thyroid dysfunction detectable by a specific test. This test give the possibility to identify women with RM in which specific therapeutic approaches could effectively improve the possibility for a successful pregnancy. PMID- 22319529 TI - Periradicular Tissue Responses to Biologically Active Molecules or MTA When Applied in Furcal Perforation of Dogs' Teeth. AB - The aim of this study was the comparative evaluation of inflammatory reactions and tissue responses to four growth factors, or mineral trioxide aggregate (MTA), or a zinc-oxide-eugenol-based cement (IRM) as controls, when used for the repair of furcal perforations in dogs' teeth. Results showed significantly higher inflammatory cell response in the transforming growth factorbeta1 (TGFbeta1) and zinc-oxide-eugenol-based cement (IRM) groups and higher rates of epithelial proliferation in the TGFbeta1, basic fibroblast growth factor (bFGF), and insulin growth factor-I (IGF-I) groups compared to the MTA. Significantly higher rates of bone formation were found in the control groups compared to the osteogenic protein-1 (OP-1). Significantly higher rates of cementum formation were observed in the IGF-I and bFGF groups compared to the IRM. None of the biologically active molecules can be suggested for repairing furcal perforations, despite the fact that growth factors exerted a clear stimulatory effect on cementum formation and inhibited collagen capsule formation. MTA exhibited better results than the growth factors. PMID- 22319530 TI - Relationship between Color and Translucency of Multishaded Dental Composite Resins. AB - The aim of the present study was to compare the translucency of different shades of two highly aesthetic multilayered restorative composite resins. In total nine shades from Esthet.X and ten shades from Filtek Supreme composite resins were chosen. Discs of each shade were prepared (N = 3) and light-cured. Total and diffuse transmittance values for each sample were measured. Statistical analysis showed that the opaque dentine shades of both composites were the least translucent and the enamel shades had the highest translucency. There was a significant decrease in translucency from A2 to C2 of regular body shades and also from A4 to C4 of opaque dentine shades of Esthet.X composite resin. Grey enamel shade had a significantly higher diffuse translucency compared to clear and yellow enamel shades. There was a significant decrease in translucency from A2B to D2B and also in diffuse translucency from A4D to C6D shades of Filtek Supreme composite resin. It can be concluded that the color of the composite resins tested in this study had a significant effect on their translucency. Information on the translucency of different shades of composite resins can be very useful for the clinicians in achieving optimal esthetic restorative outcome. PMID- 22319531 TI - Turnover of focal adhesions and cancer cell migration. AB - Cells are usually surrounded by the extracellular matrix (ECM), and adhesion of the cells to the ECM is a key step in their migration through tissues. Integrins are important receptors for the ECM and form structures called focal adhesions (FAs). Formation and disassembly of FAs are regulated dynamically during cell migration. Adhesion to the ECM has been studied mainly using cells cultured on an ECM-coated substratum, where the rate of cell migration is determined by the turnover of FAs. However, the molecular events underlying the disassembly of FAs are less well understood. We have recently identified both a new regulator of this disassembly process and its interaction partners. Here, we summarize our understanding of FA disassembly by focusing on the proteins implicated in this process. PMID- 22319532 TI - Improving TCR Gene Therapy for Treatment of Haematological Malignancies. AB - Adoptive immunotherapy using TCR gene modified T cells may allow separation of beneficial Graft versus tumour responses from harmful GvHD. Improvements to this include methods to generate high avidity or high affinity TCR, improvements in vector design and reduction in mispairing. Following adoptive transfer, TCR transduced T cells must be able to survive and persist in vivo to give most effective antitumour responses. Central memory or naive T cells have both been shown to be more effective than effector cells at expanding and persisting in vivo. Lymphodepletion may enhance persistence of transferred T cell populations. TCR gene transfer can be used to redirect CD4 helper T cells, and these could be used in combination with CD8+ tumour specific T cells to provide help for the antitumour response. Antigen specific T regulatory T cells can also be generated by TCR gene transfer and could be used to suppress unwanted alloresponses. PMID- 22319533 TI - A role for bcl-2 in notch1-dependent transcription in thymic lymphoma cells. AB - Notch1 is a transcription factor important for T-cell development. Notch1 is active in double negative (DN) thymocytes, while being depressed in double positive (DP) thymocytes. Synchronously, the expression of Bcl-2 becomes downregulated during the transition from DN to DP thymocytes. We previously observed that overexpression of an intracellular active Notch1 (ICN) in Bcl-2 positive 2B4 T cells leads to the transcription of Notch1-regulated genes. However, these genes were not induced in Bcl-2-negative DP PD1.6 thymic lymphoma cells overexpressing ICN. Here we show that, when Bcl-2 is simultaneously introduced into these cells, Notch-regulated genes are transcribed. Only in the presence of both Bcl-2 and ICN, PD1.6 thymic lymphoma cells become resistant to glucocorticoid (GC)-induced apoptosis. Our data suggest that Bcl-2 plays a role in modulating Notch1 function in T cells. PMID- 22319534 TI - Molecular analysis of the bacterial communities in crude oil samples from two brazilian offshore petroleum platforms. AB - Crude oil samples with high- and low-water content from two offshore platforms (PA and PB) in Campos Basin, Brazil, were assessed for bacterial communities by 16S rRNA gene-based clone libraries. RDP Classifier was used to analyze a total of 156 clones within four libraries obtained from two platforms. The clone sequences were mainly affiliated with Gammaproteobacteria (78.2% of the total clones); however, clones associated with Betaproteobacteria (10.9%), Alphaproteobacteria (9%), and Firmicutes (1.9%) were also identified. Pseudomonadaceae was the most common family affiliated with these clone sequences. The sequences were further analyzed by MOTHUR, yielding 81 operational taxonomic units (OTUs) grouped at 97% stringency. Richness estimators also calculated by MOTHUR indicated that oil samples with high-water content were the most diverse. Comparison of bacterial communities present in these four samples using LIBSHUFF and Principal Component Analysis (PCA) indicated that the water content significantly influenced the community structure only of crude oil obtained from PA. Differences between PA and PB libraries were observed, suggesting the importance of the oil field as a driver of community composition in this habitat. PMID- 22319535 TI - Electron beam irradiation dose dependently damages the bacillus spore coat and spore membrane. AB - Effective control of spore-forming bacilli begs suitable physical or chemical methods. While many spore inactivation techniques have been proven effective, electron beam (EB) irradiation has been frequently chosen to eradicate Bacillus spores. Despite its widespread use, there are limited data evaluating the effects of EB irradiation on Bacillus spores. To study this, B. atrophaeus spores were purified, suspended in sterile, distilled water, and irradiated with EB (up to 20 kGy). Irradiated spores were found (1) to contain structural damage as observed by electron microscopy, (2) to have spilled cytoplasmic contents as measured by spectroscopy, (3) to have reduced membrane integrity as determined by fluorescence cytometry, and (4) to have fragmented genomic DNA as measured by gel electrophoresis, all in a dose-dependent manner. Additionally, cytometry data reveal decreased spore size, increased surface alterations, and increased uptake of propidium iodide, with increasing EB dose, suggesting spore coat alterations with membrane damage, prior to loss of spore viability. The present study suggests that EB irradiation of spores in water results in substantial structural damage of the spore coat and inner membrane, and that, along with DNA fragmentation, results in dose-dependent spore inactivation. PMID- 22319536 TI - Transtympanic Electrocochleography for the Diagnosis of Meniere's Disease. AB - This paper evaluated the diagnostic power of electrocochleography (ECochG) in detecting Meniere's disease (MD) as compared with two subjective assessment methods, including the clinical guidelines provided by the American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing Equilibrium and the Gibson score. A retrospective study of 250 suspected MD cases was conducted. The agreement between the three assessment methods was found to be relatively high, with a total reliability being higher than 70%. Participants who tested "positive" with ECochG exhibited a higher occurrence rate of asymmetric hearing threshold as well as the four MD symptoms, namely, vertigo, hearing loss, tinnitus, and aural fullness. The "positive" ECochG group also showed a high correlation between the ECochG measures in response to stimuli at adjacent frequency ranges, suggesting that the interfrequency ECochG correspondence may be sensitive to the presence of endolymphatic hydrops and thus may serve as a useful diagnostic marker for MD. PMID- 22319537 TI - Pure Motor Monoparesis in the Leg due to a Lateral Medullary Infarction. AB - A 76-year-old man with essential hypertension abruptly presented with slight left sided leg weakness, despite normal strength in the other extremities. Left-sided Babinski's reflex was detected. There were no other neurologic abnormalities. Cranial magnetic resonance imaging demonstrated a small infarction in the lower lateral medulla oblongata on the left side. Cranial magnetic resonance angiography demonstrated an absence of flow of the left vertebral artery. He became asymptomatic within 10 days under intravenous antiplatelet agent. The corticospinal tract fibers innervating the lower extremity caudal to the pyramidal decussation might be involved. We emphasize that this is a first reported case of pure motor monoparesis in the leg due to lateral medullary infarction. PMID- 22319538 TI - Reversible myocarditis after black widow spider envenomation. AB - Black widow spiders can cause variable clinical scenarios from local damage to very serious conditions including death. Acute myocardial damage is rarely observed and its prognostic significance is not known. We report a rare case of a 35-year-old man who developed an acute myocarditis with cardiogenic pulmonary edema requiring mechanical ventilation caused by black widow spider's envenomation. The patient was previously healthy. The clinical course was associated with systemic and cardiovascular complaints. His electrocardiogram revealed ST-segment elevation with T-wave amplitude. The plasma concentrations of cardiac enzymes were elevated. His first echocardiography showed hypokinesis of the left ventricle (left ventricle ejection fraction 48%). Magnetic resonance imaging showed also focal myocardial injury of the LV. There was progressive improvement in cardiac traces, biochemical and echocardiographical values (second left ventricle ejection fraction increased to 50%). Myocardial involvement after a spider bite is rare and can cause death. The exact mechanism of this myocarditis is unknown. We report a rare case of acute myocarditis with cardiogenic pulmonary edema requiring mechanical ventilation caused by black widow spider's envenomation. We objectively documented progressive clinical and electrical improvement. PMID- 22319539 TI - How can the microbiologist help in diagnosing neonatal sepsis? AB - Neonatal sepsis can be classified into two subtypes depending upon whether the onset of symptoms is before 72 hours of life (early-onset neonatal sepsis-EONS) or later (late-onset neonatal sepsis-LONS). These definitions have contributed greatly to diagnosis and treatment by identifying which microorganisms are likely to be responsible for sepsis during these periods and the expected outcomes of infection. This paper focuses on the tools that microbiologist can offer to diagnose and eventually prevent neonatal sepsis. Here, we discuss the advantages and limitation of the blood culture, the actual gold standard for sepsis diagnosis. In addition, we examine the utility of molecular techniques in the diagnosis and management of neonatal sepsis. PMID- 22319540 TI - Mechanisms of fetal programming in hypertension. AB - Events that occur in the early fetal environment have been linked to long-term health and lifespan consequences in the adult. Intrauterine growth restriction (IUGR), which may occur as a result of nutrient insufficiency, exposure to hormones, or disruptions in placental structure or function, may induce the fetus to alter its developmental program in order to adapt to the new conditions. IUGR may result in a decrease in the expression of genes that are responsible for nephrogenesis as nutrients are rerouted to the development of more essential organs. Fetal survival under these conditions often results in low birth weight and a deficit in nephron endowment, which are associated with hypertension in adults. Interestingly, male IUGR offspring appear to be more severely affected than females, suggesting that sex hormones may be involved. The processes of fetal programming of hypertension are complex, and we are only beginning to understand the underlying mechanisms. PMID- 22319541 TI - Infection by CXCR4-Tropic Human Immunodeficiency Virus Type 1 Is Inhibited by the Cationic Cell-Penetrating Peptide Derived from HIV-1 Tat. AB - Cell-penetrating peptides (CPP), which are short peptides that are capable of crossing the plasma membrane of a living cell, are under development as delivery vehicles for therapeutic agents that cannot themselves enter the cell. One well studied CPP is the 10-amino acid peptide derived from the human immunodeficiency virus type 1 (HIV-1) Tat protein. In experiments to test the hypothesis that multiple cationic amino acids within Tat peptide confer antiviral activity against HIV-1, introduction of Tat peptide resulted in concentration-dependent inhibition of HIV-1 IIIB infection. Using Tat peptide variants containing arginine substitutions for two nonionic residues and two lysine residues, HIV-1 inhibition experiments demonstrated a direct relationship between cationic charge and antiviral potency. These studies of Tat peptide as an antiviral agent raise new questions about the role of Tat in HIV-1 replication and provide a starting point for the development of CPPs as novel HIV-1 inhibitors. PMID- 22319543 TI - Usage and attitudes of physicians in Japan concerning traditional Japanese medicine (kampo medicine): a descriptive evaluation of a representative questionnaire-based survey. AB - Kampo medicine has been the primary medical model in Japan until the mid 1800s, regained a prominent role in today's Japanese medical system. Today, 148 herbal Kampo formulas can be prescribed under the national health insurance system, allowing physicians to integrate Kampo in their daily practice. This article aims to provide information about the extent to which Kampo is now used in clinics throughout Japan and about physician's current attitudes toward Kampo. We used the results of a 2008 survey that was administered to physicians throughout Japan (n = 684). The data showed that 83.5% of physicians currently use Kampo in the clinic, although the distribution of physicians who use Kampo differ widely depending on the specialty and provided a breakdown of Kampo usage by specialty. It will be interesting to see how each specialty incorporates Kampo into its respective field as Kampo continues to play a pertinent role in Japanese medical system. PMID- 22319544 TI - Mathematical Distinction in Action Potential between Primo-Vessels and Smooth Muscle. AB - We studied the action potential of Primo-vessels in rats to determine the electrophysiological characteristics of these structures. We introduced a mathematical analysis method, a normalized Fourier transform that displays the sine and cosine components separately, to compare the action potentials of Primo vessels with those for the smooth muscle. We found that Primo-vessels generated two types of action potential pulses that differed from those of smooth muscle: (1) Type I pulse had rapid depolarizing and repolarizing phases, and (2) Type II pulse had a rapid depolarizing phase and a gradually slowing repolarizing phase. PMID- 22319545 TI - Xiaoyaosan decoction, a traditional chinese medicine, inhibits oxidative-stress induced hippocampus neuron apoptosis in vitro. AB - Xiaoyaosan (XYS) decoction is a famous prescription for the treatment of mental disorders in China. In this experiment, we explored the way in which XYS decoction-reverse hippocampus neuron apoptosis in vitro. We used XYS decoction containing serum to treat oxidative-stress-induced hippocampus neuron apoptosis and used immunofluorescence to determine the concentration of free calcium, mitochondrial membrane potential, and apoptotic rate of neuron. Results showed that 3-hour oxidative stress decrease mitochondrial membrane potential, increase the concentration of free calcium and apoptotic rate of neuron via triggering pathological changes of nucleus such as karyorrhexis, karyopyknosis. Low, medium, high dose of XYS-decoction-containing serum could reverse these phenomenon, and the effect of low-dose XYS-decoction-containing serum was significant in improving mitochondrial membrane potential and apoptotic rate of neuron. These findings suggest that XYS decoction may be helpful in reducing oxidative-stress induced hippocampus neuron apoptosis. PMID- 22319542 TI - Exploiting the interplay between innate and adaptive immunity to improve immunotherapeutic strategies for Epstein-Barr-virus-driven disorders. AB - The recent demonstration that immunotherapeutic approaches may be clinically effective for cancer patients has renewed the interest for this strategy of intervention. In particular, clinical trials using adoptive T-cell therapies disclosed encouraging results, particularly in the context of Epstein-Barr-virus- (EBV-) related tumors. Nevertheless, the rate of complete clinical responses is still limited, thus stimulating the development of more effective therapeutic protocols. Considering the relevance of innate immunity in controlling both infections and cancers, innovative immunotherapeutic approaches should take into account also this compartment to improve clinical efficacy. Evidence accumulated so far indicates that innate immunity effectors, particularly NK cells, can be exploited with therapeutic purposes and new targets have been recently identified. We herein review the complex interactions between EBV and innate immunity and summarize the therapeutic strategies involving both adaptive and innate immune system, in the light of a fruitful integration between these immunotherapeutic modalities for a better control of EBV-driven tumors. PMID- 22319546 TI - Plant stem bark extractivism in the northeast semiarid region of Brazil: a new aport to utilitarian redundancy model. AB - We use the model of utilitarian redundancy as a basis for research. This model provides predictions that have not been tested by other research. In this sense, we sought to investigate the stem bark extraction between preferred and less preferred species by a rural community in Caatinga environment. In addition, we sought to explain local preferences to observe if preferred plants have a higher content of tannins than less-preferred species. For this, we selected seven preferred species and seven less-preferred species from information obtained from semistructured interviews applied to 49 informants. Three areas of vegetation around the community were also selected, in which individuals were tagged, and were measured the diameter at ground level (DGL) diameter at breast height (DBH), and measurements of available and extracted bark areas. Samples of bark of the species were also collected for the evaluation of tannin content, obtained by the method of radial diffusion. From the results, the preferred species showed a greater area of bark removed. However, the tannin content showed no significant differences between preferred and less-preferred plants. These results show there is a relationship between preference and use, but this preference is not related to the total tannins content. PMID- 22319547 TI - The cortical and striatal gene expression profile of 100 hz electroacupuncture treatment in 6-hydroxydopamine-induced Parkinson's disease model. AB - Electroacupuncture (EA), especially high-frequency EA, has frequently been used as an alternative therapy for Parkinson disease (PD) and is reportedly effective for alleviating motor symptoms in patients and PD models. However, the molecular mechanism underlying its effectiveness is not completely understood. To implement a full-scale search for the targets of 100 Hz EA, we selected rat models treated with 6-hydroxydopamine into the unilateral MFB, which mimic end-stage PD. High throughput microarray analysis was then used to uncover the regulated targets in the cortex and striatum after 4-week EA treatment. In the differentially regulated transcripts, the proportion of recovered expression profiles in the genes, the functional categories of targets in different profiles, and the affected pathways were analyzed. Our results suggested that the recovery of homeostasis in the transcript network and many regulated functional clusters in the cortex and striatum after EA treatment may contribute to the behavioral improvement of PD rats. PMID- 22319548 TI - The finite element method applied to a problem of blood flow in vessels. AB - We use the finite element method to solve a convection-diffusion equation when convection is dominating, a problem which describes the behavior of the concentration of a solute in a blood vessel. A new technique for computing the discrete problem is used. PMID- 22319549 TI - Simulation of spread and control of lesions in brain. AB - A simulation model for the spread and control of lesions in the brain is constructed using a planar network (graph) representation for the central nervous system (CNS). The model is inspired by the lesion structures observed in the case of multiple sclerosis (MS), a chronic disease of the CNS. The initial lesion site is at the center of a unit square and spreads outwards based on the success rate in damaging edges (axons) of the network. The damaged edges send out alarm signals which, at appropriate intensity levels, generate programmed cell death. Depending on the extent and timing of the programmed cell death, the lesion may get controlled or aggravated akin to the control of wild fires by burning of peripheral vegetation. The parameter phase space of the model shows smooth transition from uncontrolled situation to controlled situation. The simulations show that the model is capable of generating a wide variety of lesion growth and arrest scenarios. PMID- 22319550 TI - Functional magnetic resonance imaging for imaging neural activity in the human brain: the annual progress. AB - Functional magnetic resonance imaging (fMRI) is recently developed and applied to measure the hemodynamic response related to neural activity. The fMRI can not only noninvasively record brain signals without risks of ionising radiation inherent in other scanning methods, such as CT or PET scans, but also record signal from all regions of the brain, unlike EEG/MEG which are biased towards the cortical surface. This paper introduces the fundamental principles and summarizes the research progress of the last year for imaging neural activity in the human brain. Aims of functional analysis of neural activity from fMRI include biological findings, functional connectivity, vision and hearing research, emotional research, neurosurgical planning, pain management, and many others. Besides formulations and basic processing methods, models and strategies of processing technology are introduced, including general linear model, nonlinear model, generative model, spatial pattern analysis, statistical analysis, correlation analysis, and multimodal combination. This paper provides readers the most recent representative contributions in the area. PMID- 22319551 TI - Animal virus schemes for translation dominance. AB - Viruses have adapted a broad range of unique mechanisms to modulate the cellular translational machinery to ensure viral translation at the expense of cellular protein synthesis. Many of these promote virus-specific translation by use of molecular tags on viral mRNA such as internal ribosome entry sites (IRES) and genome-linked viral proteins (VPg) that bind translation machinery components in unusual ways and promote RNA circularization. This review describes recent advances in understanding some of the mechanisms in which animal virus mRNAs gain an advantage over cellular transcripts, including new structural and biochemical insights into IRES function and novel proteins that function as alternate met tRNA(i)(met) carriers in translation initiation. Comparisons between animal and plant virus mechanisms that promote translation of viral mRNAs are discussed. PMID- 22319554 TI - A Novel YY1-miR-1 regulatory circuit in skeletal myogenesis revealed by genome wide prediction of YY1-miRNA network. AB - microRNAs (miRNAs) are non-coding RNAs that regulate gene expression post transcriptionally, and mounting evidence supports the prevalence and functional significance of their interplay with transcription factors (TFs). Here we describe the identification of a regulatory circuit between muscle miRNAs (miR-1, miR-133 and miR-206) and Yin Yang 1 (YY1), an epigenetic repressor of skeletal myogenesis in mouse. Genome-wide identification of potential down-stream targets of YY1 by combining computational prediction with expression profiling data reveals a large number of putative miRNA targets of YY1 during skeletal myoblasts differentiation into myotubes with muscle miRs ranking on top of the list. The subsequent experimental results demonstrate that YY1 indeed represses muscle miRs expression in myoblasts and the repression is mediated through multiple enhancers and recruitment of Polycomb complex to several YY1 binding sites. YY1 regulating miR-1 is functionally important for both C2C12 myogenic differentiation and injury-induced muscle regeneration. Furthermore, we demonstrate that miR-1 in turn targets YY1, thus forming a negative feedback loop. Together, these results identify a novel regulatory circuit required for skeletal myogenesis and reinforce the idea that regulatory circuitries involving miRNAs and TFs are prevalent mechanisms. PMID- 22319555 TI - Anatomical and functional deficits in patients with amnestic mild cognitive impairment. AB - BACKGROUND: Anatomical and functional deficits have been studied in patients with amnestic mild cognitive impairment (MCI). However, it is unclear whether and how the anatomical deficits are related to the functional alterations. Present study aims to characterize the association between anatomical and functional deficits in MCI patients. METHODS: Seventeen amnestic MCI patients and 18 healthy aging controls were scanned using a T1 Weighted MPRAGE sequence and a gradient-echo echo-planar imaging sequence. Clinical severity of MCI patients was evaluated by using Clinical Dementia Rating, Mini Mental State Examination (MMSE), Clock Drawing Test, Auditory Verbal Learning Test and Activities of Daily Living. VBM with DARTEL was used to characterize the gray matter deficits in MCI. Regional amplitude of low-frequency (0.01-0.08 Hz) fluctuations (ALFF) was used to evaluate regional functional alteration in MCI and fractional ALFF(fALFF) in slow 4 (0.027-0.073 Hz) and slow 5 (0.01-0.027 Hz) were also calculated. RESULTS: Significantly decreased gray matter volume (GMV) was observed in amnestic MCI group mainly in bilateral prefrontal, left temporal and posterior cingulate cortex. Significant positive correlation was observed between the GMV in left inferior frontal gyrus and MMSE scores. Interestingly, decreased ALFF/fALFF was revealed in MCI group compared to controls mainly in prefrontal, left parietal regions and right fusiform gyrus, while the increased ALFF/fALFF was found in limbic and midbrain. Furthermore, the changes of fALFF in MCI in the slow-5 band were greater than those in the slow-4. No significant correlation was found between the morphometric and functional results. CONCLUSIONS: Findings from the study document that wide spread brain volume reduction accompanied with decreased and increased regional function in MCI, while the anatomical and functional changes were independently. Therefore, the combination of structural and functional MRI methods would provide complementary information and together advance our understanding of the pathophysiology underlying the symptoms of MCI. PMID- 22319556 TI - Investigation of the role of TNF-alpha converting enzyme (TACE) in the inhibition of cell surface and soluble TNF-alpha production by acute ethanol exposure. AB - Toll-like receptors (TLRs) play a fundamental role in the immune system by detecting pathogen associated molecular patterns (PAMPs) to sense host infection. Ethanol at doses relevant for humans inhibits the pathogen induced cytokine response mediated through TLRs. The current study was designed to investigate the mechanisms of this effect by determining whether ethanol inhibits TLR3 and TLR4 mediated TNF-alpha secretion through inhibition of transcription factor activation or post-transcriptional effects. In NF-kappaB reporter mice, activation of NF-kappaB in vivo by LPS was inhibited by ethanol (LPS alone yielded 170,000+/-35,300 arbitrary units of light emission; LPS plus ethanol yielded 56,120+/-16880, p = 0.04). Inhibition of protein synthesis by cycloheximide revealed that poly I:C- or LPS-induced secreted TNF-alpha is synthesized de novo, not released from cellular stores. Using real time RT-PCR, we found inhibition of LPS and poly I:C induced TNF-alpha gene transcription by ethanol. Using an inhibitor of tumor necrosis factor alpha converting enzyme (TACE), we found that shedding caused by TACE is a prerequisite for TNF-alpha release after pathogen challenge. Flow cytometry was used to investigate if ethanol decreases TNF-alpha secretion by inhibition of TACE. In cells treated with LPS, ethanol decreased both TNF-alpha cell surface expression and secretion. For example, 4.69+/-0.60% of untreated cells were positive for cell surface TNF alpha, LPS increased this to 25.18+/-0.85%, which was inhibited by ethanol (86.8 mM) to 14.29+/-0.39% and increased by a TACE inhibitor to 57.88+/-0.62%. In contrast, cells treated with poly I:C had decreased secretion of TNF-alpha but not cell surface expression. There was some evidence for inhibition of TACE by ethanol in the case of LPS, but decreased TNF-alpha gene expression seems to be the major mechanism of ethanol action in this system. PMID- 22319557 TI - Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is cytotoxic to lung cells. AB - Inhalation of Aspergillus fumigatus conidia can cause severe aspergillosis in immunosuppressed people. A. fumigatus produces a large number of secondary metabolites, some of which are airborne by conidia and whose toxicity to the respiratory tract has not been investigated. We found that spores of A. fumigatus contain five main compounds, tryptoquivaline F, fumiquinazoline C, questin, monomethylsulochrin and trypacidin. Fractionation of culture extracts using RP HPLC and LC-MS showed that samples containing questin, monomethylsulochrin and trypacidin were toxic to the human A549 lung cell line. These compounds were purified and their structure verified using NMR in order to compare their toxicity against A549 cells. Trypacidin was the most toxic, decreasing cell viability and triggering cell lysis, both effects occurring at an IC50 close to 7 uM. Trypacidin toxicity was also observed in the same concentration range on human bronchial epithelial cells. In the first hour of exposure, trypacidin initiates the intracellular formation of nitric oxide (NO) and hydrogen peroxide (H2O2). This oxidative stress triggers necrotic cell death in the following 24 h. The apoptosis pathway, moreover, was not involved in the cell death process as trypacidin did not induce apoptotic bodies or a decrease in mitochondrial membrane potential. This is the first time that the toxicity of trypacidin to lung cells has been reported. PMID- 22319558 TI - Effects of preoperative aspirin on cardiocerebral and renal complications in non emergent cardiac surgery patients: a sub-group and cohort study. AB - BACKGROUND AND OBJECTIVE: Postoperative cardiocerebral and renal complications are a major threat for patients undergoing cardiac surgery. This study was aimed to examine the effect of preoperative aspirin use on patients undergoing cardiac surgery. METHODS: An observational cohort study was performed on consecutive patients (n = 1879) receiving cardiac surgery at this institution. The patients excluded from the study were those with preoperative anticoagulants, unknown aspirin use, or underwent emergent cardiac surgery. Outcome events included were 30-day mortality, renal failure, readmission and a composite outcome--major adverse cardiocerebral events (MACE) that include permanent or transient stroke, coma, perioperative myocardial infarction (MI), heart block and cardiac arrest. RESULTS: Of all patients, 1145 patients met the inclusion criteria and were divided into two groups: those taking (n = 858) or not taking (n = 287) aspirin within 5 days preceding surgery. Patients with aspirin presented significantly more with history of hypertension, diabetes, peripheral arterial disease, previous MI, angina and older age. With propensity scores adjusted and multivariate logistic regression, however, this study showed that preoperative aspirin therapy (vs. no aspirin) significantly reduced the risk of MACE (8.4% vs. 12.5%, odds ratio [OR] 0.585, 95% CI 0.355-0.964, P = 0.035), postoperative renal failure (2.6% vs. 5.2%, OR 0.438, CI 0.203-0.945, P = 0.035) and dialysis required (0.8% vs. 3.1%, OR 0.230, CI 0.071-0.742, P = 0.014), but did not significantly reduce 30-day mortality (4.1% vs. 5.8%, OR 0.744, CI 0.376-1.472, P = 0.396) nor it increased readmissions in the patients undergoing cardiac surgery. CONCLUSIONS: Preoperative aspirin therapy is associated with a significant decrease in the risk of MACE and renal failure and did not increase readmissions in patients undergoing non-emergent cardiac surgery. PMID- 22319559 TI - Tissue-specific whole transcriptome sequencing in castor, directed at understanding triacylglycerol lipid biosynthetic pathways. AB - BACKGROUND: Storage triacylglycerols in castor bean seeds are enriched in the hydroxylated fatty acid ricinoleate. Extensive tissue-specific RNA-Seq transcriptome and lipid analysis will help identify components important for its biosynthesis. METHODOLOGY/FINDINGS: Storage triacylglycerols (TAGs) in the endosperm of developing castor (Ricinus communis) seeds are highly enriched in ricinoleic acid (18:1-OH). We have analysed neutral lipid fractions from other castor tissues using TLC, GLC and mass spectrometry. Cotyledons, like the endosperm, contain high levels of 18:1-OH in TAG. Pollen and male developing flowers accumulate TAG but do not contain 18:1-OH and leaves do not contain TAG or 18:1-OH. Analysis of acyl-CoAs in developing endosperm shows that ricinoleoyl CoA is not the dominant acyl-CoA, indicating that either metabolic channelling or enzyme substrate selectivity are important in the synthesis of tri-ricinolein in this tissue. RNA-Seq transcriptomic analysis, using Illumina sequencing by synthesis technology, has been performed on mRNA isolated from two stages of developing seeds, germinating seeds, leaf and pollen-producing male flowers in order to identify differences in lipid-metabolic pathways and enzyme isoforms which could be important in the biosynthesis of TAG enriched in 18:1-OH. This study gives comprehensive coverage of gene expression in a variety of different castor tissues. The potential role of differentially expressed genes is discussed against a background of proteins identified in the endoplasmic reticulum, which is the site of TAG biosynthesis, and transgenic studies aimed at increasing the ricinoleic acid content of TAG. CONCLUSIONS/SIGNIFICANCE: Several of the genes identified in this tissue-specific whole transcriptome study have been used in transgenic plant research aimed at increasing the level of ricinoleic acid in TAG. New candidate genes have been identified which might further improve the level of ricinoleic acid in transgenic crops. PMID- 22319560 TI - Gu-4 suppresses affinity and avidity modulation of CD11b and improves the outcome of mice with endotoxemia and sepsis. AB - BACKGROUND: Systemic leukocyte activation and disseminated leukocyte adhesion will impair the microcirculation and cause severe decrements in tissue perfusion and organ function in the process of severe sepsis. Gu-4, a lactosyl derivative, could selectively target CD11b to exert therapeutic effect in a rat model of severe burn shock. Here, we addressed whether Gu-4 could render protective effects on septic animals. METHODOLOGY/PRINCIPAL FINDINGS: On a murine model of endotoxemia induced by lipopolysaccharide (LPS), we found that the median effective dose (ED50) of Gu-4 was 0.929 mg/kg. In vivo treatment of Gu-4 after LPS challenge prominently attenuated LPS-induced lung injury and decreased lactic acid level in lung tissue. Using the ED50 of Gu-4, we also demonstrated that Gu-4 treatment significantly improved the survival rate of animals underwent sepsis induced by cecal ligation and puncture. By adhesion and transwell migration assays, we found that Gu-4 treatment inhibited the adhesion and transendothelial migration of LPS-stimulated THP-1 cells. By flow cytometry and microscopy, we demonstrated that Gu-4 treatment inhibited the exposure of active I-domain and the cluster formation of CD11b on the LPS-stimulated polymorphonuclear leukocytes. Western blot analyses further revealed that Gu-4 treatment markedly inhibited the activation of spleen tyrosine kinase in LPS-stimulated THP-1 cells. CONCLUSIONS/SIGNIFICANCE: Gu-4 improves the survival of mice underwent endotoxemia and sepsis, our in vitro investigations indicate that the possible underlying mechanism might involve the modulations of the affinity and avidity of CD11b on the leukocyte. Our findings shed light on the potential use of Gu-4, an interacting compound to CD11b, in the treatment of sepsis and septic shock. PMID- 22319561 TI - Dirichlet multinomial mixtures: generative models for microbial metagenomics. AB - We introduce Dirichlet multinomial mixtures (DMM) for the probabilistic modelling of microbial metagenomics data. This data can be represented as a frequency matrix giving the number of times each taxa is observed in each sample. The samples have different size, and the matrix is sparse, as communities are diverse and skewed to rare taxa. Most methods used previously to classify or cluster samples have ignored these features. We describe each community by a vector of taxa probabilities. These vectors are generated from one of a finite number of Dirichlet mixture components each with different hyperparameters. Observed samples are generated through multinomial sampling. The mixture components cluster communities into distinct 'metacommunities', and, hence, determine envirotypes or enterotypes, groups of communities with a similar composition. The model can also deduce the impact of a treatment and be used for classification. We wrote software for the fitting of DMM models using the 'evidence framework' (http://code.google.com/p/microbedmm/). This includes the Laplace approximation of the model evidence. We applied the DMM model to human gut microbe genera frequencies from Obese and Lean twins. From the model evidence four clusters fit this data best. Two clusters were dominated by Bacteroides and were homogenous; two had a more variable community composition. We could not find a significant impact of body mass on community structure. However, Obese twins were more likely to derive from the high variance clusters. We propose that obesity is not associated with a distinct microbiota but increases the chance that an individual derives from a disturbed enterotype. This is an example of the 'Anna Karenina principle (AKP)' applied to microbial communities: disturbed states having many more configurations than undisturbed. We verify this by showing that in a study of inflammatory bowel disease (IBD) phenotypes, ileal Crohn's disease (ICD) is associated with a more variable community. PMID- 22319562 TI - The earliest post-paleozoic freshwater bivalves preserved in coprolites from the karoo basin, South Africa. AB - BACKGROUND: Several clades of bivalve molluscs have invaded freshwaters at various times throughout Phanerozoic history. The most successful freshwater clade in the modern world is the Unionoida. Unionoids arose in the Triassic Period, sometime after the major extinction event at the End-Permian boundary and are now widely distributed across all continents except Antarctica. Until now, no freshwater bivalves of any kind were known to exist in the Early Triassic. PRINCIPAL FINDINGS: Here we report on a faunule of two small freshwater bivalve species preserved in vertebrate coprolites from the Olenekian (Lower Triassic) of the Burgersdorp Formation of the Karoo Basin, South Africa. Positive identification of these bivalves is not possible due to the limited material. Nevertheless they do show similarities with Unionoida although they fall below the size range of extant unionoids. Phylogenetic analysis is not possible with such limited material and consequently the assignment remains somewhat speculative. CONCLUSIONS: Bivalve molluscs re-invaded freshwaters soon after the End-Permian extinction event, during the earliest part of the recovery phase during the Olenekian Stage of the Early Triassic. If the specimens do represent unionoids then these Early Triassic examples may be an example of the Lilliput effect. Since the oldest incontrovertible freshwater unionoids are also from sub Saharan Africa, it is possible that this subcontinent hosted the initial freshwater radiation of the Unionoida. This find also demonstrates the importance of coprolites as microenvironments of exceptional preservation that contain fossils of organisms that would otherwise have left no trace. PMID- 22319563 TI - ECOMICS: a web-based toolkit for investigating the biomolecular web in ecosystems using a trans-omics approach. AB - Ecosystems can be conceptually thought of as interconnected environmental and metabolic systems, in which small molecules to macro-molecules interact through diverse networks. State-of-the-art technologies in post-genomic science offer ways to inspect and analyze this biomolecular web using omics-based approaches. Exploring useful genes and enzymes, as well as biomass resources responsible for anabolism and catabolism within ecosystems will contribute to a better understanding of environmental functions and their application to biotechnology. Here we present ECOMICS, a suite of web-based tools for ECosystem trans-OMICS investigation that target metagenomic, metatranscriptomic, and meta-metabolomic systems, including biomacromolecular mixtures derived from biomass. ECOMICS is made of four integrated webtools. E-class allows for the sequence-based taxonomic classification of eukaryotic and prokaryotic ribosomal data and the functional classification of selected enzymes. FT2B allows for the digital processing of NMR spectra for downstream metabolic or chemical phenotyping. Bm-Char allows for statistical assignment of specific compounds found in lignocellulose-based biomass, and HetMap is a data matrix generator and correlation calculator that can be applied to trans-omics datasets as analyzed by these and other web tools. This web suite is unique in that it allows for the monitoring of biomass metabolism in a particular environment, i.e., from macromolecular complexes (FT2DB and Bm-Char) to microbial composition and degradation (E-class), and makes possible the understanding of relationships between molecular and microbial elements (HetMap). This website is available to the public domain at: https://database.riken.jp/ecomics/. PMID- 22319564 TI - Bezielle selectively targets mitochondria of cancer cells to inhibit glycolysis and OXPHOS. AB - Bezielle (BZL101) is a candidate oral drug that has shown promising efficacy and excellent safety in the early phase clinical trials for advanced breast cancer. Bezielle is an aqueous extract from the herb Scutellaria barbata. We have reported previously that Bezielle was selectively cytotoxic to cancer cells while sparing non-transformed cells. In tumor, but not in non-transformed cells, Bezielle induced generation of ROS and severe DNA damage followed by hyperactivation of PARP, depletion of the cellular ATP and NAD, and inhibition of glycolysis. We show here that tumor cells' mitochondria are the primary source of reactive oxygen species induced by Bezielle. Treatment with Bezielle induces progressively higher levels of mitochondrial superoxide as well as peroxide-type ROS. Inhibition of mitochondrial respiration prevents generation of both types of ROS and protects cells from Bezielle-induced death. In addition to glycolysis, Bezielle inhibits oxidative phosphorylation in tumor cells and depletes mitochondrial reserve capacity depriving cells of the ability to produce ATP. Tumor cells lacking functional mitochondria maintain glycolytic activity in presence of Bezielle thus supporting the hypothesis that mitochondria are the primary target of Bezielle. The metabolic effects of Bezielle towards normal cells are not significant, in agreement with the low levels of oxidative damage that Bezielle inflicts on them. Bezielle is therefore a drug that selectively targets cancer cell mitochondria, and is distinguished from other such drugs by its ability to induce not only inhibition of OXPHOS but also of glycolysis. This study provides a better understanding of the mechanism of Bezielle's cytotoxicity, and the basis of its selectivity towards cancer cells. PMID- 22319565 TI - TANGLE: two-level support vector regression approach for protein backbone torsion angle prediction from primary sequences. AB - Protein backbone torsion angles (Phi) and (Psi) involve two rotation angles rotating around the C(alpha)-N bond (Phi) and the C(alpha)-C bond (Psi). Due to the planarity of the linked rigid peptide bonds, these two angles can essentially determine the backbone geometry of proteins. Accordingly, the accurate prediction of protein backbone torsion angle from sequence information can assist the prediction of protein structures. In this study, we develop a new approach called TANGLE (Torsion ANGLE predictor) to predict the protein backbone torsion angles from amino acid sequences. TANGLE uses a two-level support vector regression approach to perform real-value torsion angle prediction using a variety of features derived from amino acid sequences, including the evolutionary profiles in the form of position-specific scoring matrices, predicted secondary structure, solvent accessibility and natively disordered region as well as other global sequence features. When evaluated based on a large benchmark dataset of 1,526 non homologous proteins, the mean absolute errors (MAEs) of the Phi and Psi angle prediction are 27.8 degrees and 44.6 degrees , respectively, which are 1% and 3% respectively lower than that using one of the state-of-the-art prediction tools ANGLOR. Moreover, the prediction of TANGLE is significantly better than a random predictor that was built on the amino acid-specific basis, with the p-value<1.46e 147 and 7.97e-150, respectively by the Wilcoxon signed rank test. As a complementary approach to the current torsion angle prediction algorithms, TANGLE should prove useful in predicting protein structural properties and assisting protein fold recognition by applying the predicted torsion angles as useful restraints. TANGLE is freely accessible at http://sunflower.kuicr.kyoto u.ac.jp/~sjn/TANGLE/. PMID- 22319566 TI - CAPRG: sequence assembling pipeline for next generation sequencing of non-model organisms. AB - Our goal is to introduce and describe the utility of a new pipeline "Contigs Assembly Pipeline using Reference Genome" (CAPRG), which has been developed to assemble "long sequence reads" for non-model organisms by leveraging a reference genome of a closely related phylogenetic relative. To facilitate this effort, we utilized two avian transcriptomic datasets generated using ROCHE/454 technology as test cases for CAPRG assembly. We compared the results of CAPRG assembly using a reference genome with the results of existing methods that utilize de novo strategies such as VELVET, PAVE, and MIRA by employing parameter space comparisons (intra-assembling comparison). CAPRG performed as well or better than the existing assembly methods based on various benchmarks for "gene-hunting." Further, CAPRG completed the assemblies in a fraction of the time required by the existing assembly algorithms. Additional advantages of CAPRG included reduced contig inflation resulting in lower computational resources for annotation, and functional identification for contigs that may be categorized as "unknowns" by de novo methods. In addition to providing evaluation of CAPRG performance, we observed that the different assembly (inter-assembly) results could be integrated to enhance the putative gene coverage for any transcriptomics study. PMID- 22319567 TI - Defining the boundaries of normal thrombin generation: investigations into hemostasis. AB - In terms of its soluble precursors, the coagulation proteome varies quantitatively among apparently healthy individuals. The significance of this variability remains obscure, in part because it is the backdrop against which the hemostatic consequences of more dramatic composition differences are studied. In this study we have defined the consequences of normal range variation of components of the coagulation proteome by using a mechanism-based computational approach that translates coagulation factor concentration data into a representation of an individual's thrombin generation potential. A novel graphical method is used to integrate standard measures that characterize thrombin generation in both empirical and computational models (e.g max rate, max level, total thrombin, time to 2 nM thrombin ("clot time")) to visualize how normal range variation in coagulation factors results in unique thrombin generation phenotypes. Unique ensembles of the 8 coagulation factors encompassing the limits of normal range variation were used as initial conditions for the computational modeling, each ensemble representing "an individual" in a theoretical healthy population. These "individuals" with unremarkable proteome composition was then compared to actual normal and "abnormal" individuals, i.e. factor ensembles measured in apparently healthy individuals, actual coagulopathic individuals or artificially constructed factor ensembles representing individuals with specific factor deficiencies. A sensitivity analysis was performed to rank either individual factors or all possible pairs of factors in terms of their contribution to the overall distribution of thrombin generation phenotypes. Key findings of these analyses include: normal range variation of coagulation factors yields thrombin generation phenotypes indistinguishable from individuals with some, but not all, coagulopathies examined; coordinate variation of certain pairs of factors within their normal ranges disproportionately results in extreme thrombin generation phenotypes, implying that measurement of a smaller set of factors may be sufficient to identify individuals with aberrant thrombin generation potential despite normal coagulation proteome composition. PMID- 22319568 TI - Novel functional MAR elements of double minute chromosomes in human ovarian cells capable of enhancing gene expression. AB - Double minute chromosomes or double minutes (DMs) are cytogenetic hallmarks of extrachromosomal genomic amplification and play a critical role in tumorigenesis. Amplified copies of oncogenes in DMs have been associated with increased growth and survival of cancer cells but DNA sequences in DMs which are mostly non-coding remain to be characterized. Following sequencing and bioinformatics analyses, we have found 5 novel matrix attachment regions (MARs) in a 682 kb DM in the human ovarian cancer cell line, UACC-1598. By electrophoretic mobility shift assay (EMSA), we determined that all 5 MARs interact with the nuclear matrix in vitro. Furthermore, qPCR analysis revealed that these MARs associate with the nuclear matrix in vivo, indicating that they are functional. Transfection of MARs constructs into human embryonic kidney 293T cells showed significant enhancement of gene expression as measured by luciferase assay, suggesting that the identified MARS, particularly MARs 1 to 4, regulate their target genes in vivo and are potentially involved in DM-mediated oncogene activation. PMID- 22319569 TI - PET/CT imaging of c-Myc transgenic mice identifies the genotoxic N-nitroso diethylamine as carcinogen in a short-term cancer bioassay. AB - BACKGROUND: More than 100,000 chemicals are in use but have not been tested for their safety. To overcome limitations in the cancer bioassay several alternative testing strategies are explored. The inability to monitor non-invasively onset and progression of disease limits, however, the value of current testing strategies. Here, we report the application of in vivo imaging to a c-Myc transgenic mouse model of liver cancer for the development of a short-term cancer bioassay. METHODOLOGY/PRINCIPAL FINDINGS: MUCT and 18F-FDG MUPET were used to detect and quantify tumor lesions after treatment with the genotoxic carcinogen NDEA, the tumor promoting agent BHT or the hepatotoxin paracetamol. Tumor growth was investigated between the ages of 4 to 8.5 months and contrast-enhanced MUCT imaging detected liver lesions as well as metastatic spread with high sensitivity and accuracy as confirmed by histopathology. Significant differences in the onset of tumor growth, tumor load and glucose metabolism were observed when the NDEA treatment group was compared with any of the other treatment groups. NDEA treatment of c-Myc transgenic mice significantly accelerated tumor growth and caused metastatic spread of HCC in to lung but this treatment also induced primary lung cancer growth. In contrast, BHT and paracetamol did not promote hepatocarcinogenesis. CONCLUSIONS/SIGNIFICANCE: The present study evidences the accuracy of in vivo imaging in defining tumor growth, tumor load, lesion number and metastatic spread. Consequently, the application of in vivo imaging techniques to transgenic animal models may possibly enable short-term cancer bioassays to significantly improve hazard identification and follow-up examinations of different organs by non-invasive methods. PMID- 22319570 TI - Longitudinal assessment of antisaccades in patients with multiple sclerosis. AB - We have previously demonstrated that assessment of antisaccades (AS) provides not only measures of motor function in multiple sclerosis (MS), but measures of cognitive control processes in particular, attention and working memory. This study sought to demonstrate the potential for AS measures to sensitively reflect change in functional status in MS. Twenty-four patients with relapsing-remitting MS and 12 age-matched controls were evaluated longitudinally using an AS saccade task. Compared to control subjects, a number of saccade parameters changed significantly over a two year period for MS patients. These included saccade error rates, latencies, and accuracy measures. Further, for MS patients, correlations were retained between OM measures and scores on the PASAT, which is considered the reference task for the cognitive evaluation of MS patients. Notably, EDSS scores for these patients did not change significantly over this period. These results demonstrate that OM measures may reflect disease evolution in MS, in the absence of clinically evident changes as measured using conventional techniques. With replication, these markers could ultimately be developed into a cost-effective, non-invasive, and well tolerated assessment tool to assist in confirming progression early in the disease process, and in measuring and predicting response to therapy. PMID- 22319571 TI - Sequence heterogeneity in NS5A of hepatitis C virus genotypes 2a and 2b and clinical outcome of pegylated-interferon/ribavirin therapy. AB - Pegylated-interferon plus ribavirin (PEG-IFN/RBV) therapy is a current standard treatment for chronic hepatitis C. We previously reported that the viral sequence heterogeneity of part of NS5A, referred to as the IFN/RBV resistance-determining region (IRRDR), and a mutation at position 70 of the core protein of hepatitis C virus genotype 1b (HCV-1b) are significantly correlated with the outcome of PEG IFN/RBV treatment. Here, we aimed to investigate the impact of viral genetic variations within the NS5A and core regions of other genotypes, HCV-2a and HCV 2b, on PEG-IFN/RBV treatment outcome. Pretreatment sequences of NS5A and core regions were analyzed in 112 patients infected with HCV-2a or HCV-2b, who were treated with PEG-IFN/RBV for 24 weeks and followed up for another 24 weeks. The results demonstrated that HCV-2a isolates with 4 or more mutations in IRRDR (IRRDR[2a]>=4) was significantly associated with rapid virological response at week 4 (RVR) and sustained virological response (SVR). Also, another region of NS5A that corresponds to part of the IFN sensitivity-determining region (ISDR) plus its carboxy-flanking region, which we referred to as ISDR/+C[2a], was significantly associated with SVR in patients infected with HCV-2a. Multivariate analysis revealed that IRRDR[2a]>=4 was the only independent predictive factor for SVR. As for HCV-2b infection, an N-terminal half of IRRDR having two or more mutations (IRRDR[2b]/N>=2) was significantly associated with RVR, but not with SVR. No significant correlation was observed between core protein polymorphism and PEG-IFN/RBV treatment outcome in HCV-2a or HCV-2b infection. CONCLUSION: The present results suggest that sequence heterogeneity of NS5A of HCV-2a (IRRDR[2a]>=4 and ISDR/+C[2a]), and that of HCV-2b (IRRDR[2b]/N>=2) to a lesser extent, is involved in determining the viral sensitivity to PEG-IFN/RBV therapy. PMID- 22319572 TI - Coherence potentials encode simple human sensorimotor behavior. AB - Recent work has shown that large amplitude negative periods in the local field potential (nLFPs) are able to spread in saltatory manner across large distances in the cortex without distortion in their temporal structure forming 'coherence potentials'. Here we analysed subdural electrocorticographic (ECoG) signals recorded at 59 sites in the sensorimotor cortex in the left hemisphere of a human subject performing a simple visuomotor task (fist clenching and foot dorsiflexion) to understand how coherence potentials arising in the recordings relate to sensorimotor behavior. In all behaviors we found a particular coherence potential (i.e. a cascade of a particular nLFP wave pattern) arose consistently across all trials with temporal specificity. During contrateral fist clenching, but not the foot dorsiflexion or ipsilateral fist clenching, the coherence potential most frequently originated in the hand representation area in the somatosensory cortex during the anticipation and planning periods of the trial, moving to other regions during the actual motor behavior. While these 'expert' sites participated more consistently, other sites participated only a small fraction of the time. Furthermore, the timing of the coherence potential at the hand representation area after onset of the cue predicted the timing of motor behavior. We present the hypothesis that coherence potentials encode information relevant for behavior and are generated by the 'expert' sites that subsequently broadcast to other sites as a means of 'sharing knowledge'. PMID- 22319573 TI - The unconserved groucho central region is essential for viability and modulates target gene specificity. AB - Groucho (Gro) is a Drosophila corepressor required by numerous DNA-binding repressors, many of which are distributed in gradients and provide positional information during development. Gro contains well-conserved domains at its N- and C-termini, and a poorly conserved central region that includes the GP, CcN, and SP domains. All lethal point mutations in gro map to the conserved regions, leading to speculation that the unconserved central domains are dispensable. However, our sequence analysis suggests that the central domains are disordered leading us to suspect that the lack of lethal mutations in this region reflects a lack of order rather than an absence of essential functions. In support of this conclusion, genomic rescue experiments with Gro deletion variants demonstrate that the GP and CcN domains are required for viability. Misexpression assays using these same deletion variants show that the SP domain prevents unrestrained and promiscuous repression by Gro, while the GP and CcN domains are indispensable for repression. Deletion of the GP domain leads to loss of nuclear import, while deletion of the CcN domain leads to complete loss of repression. Changes in Gro activity levels reset the threshold concentrations at which graded repressors silence target gene expression. We conclude that co-regulators such as Gro are not simply permissive components of the repression machinery, but cooperate with graded DNA-binding factors in setting borders of gene expression. We suspect that disorder in the Gro central domains may provide the flexibility that allows this region to mediate multiple interactions required for repression. PMID- 22319574 TI - Clonal immune responses of Mycobacterium-specific gammadelta T cells in tuberculous and non-tuberculous tissues during M. tuberculosis infection. AB - BACKGROUND: We previously demonstrated that unvaccinated macaques infected with large-dose M.tuberculosis(Mtb) exhibited delays for pulmonary trafficking of Ag specific alphabeta and gammadelta T effector cells, and developed severe lung tuberculosis(TB) and "secondary" Mtb infection in remote organs such as liver and kidney. Despite delays in lungs, local immunity in remote organs may accumulate since progressive immune activation after pulmonary Mtb infection may allow IFNgamma-producing gammadelta T cells to adequately develop and traffic to lately infected remote organs. As initial efforts to test this hypothesis, we comparatively examined TCR repertoire/clonality, tissue trafficking and effector function of Vgamma2Vdelta2 T cells in lung with severe TB and in liver/kidney without apparent TB. METHODOLOGY/PRINCIPAL FINDINGS: We utilized conventional infection-immunity approaches in macaque TB model, and employed our decades-long expertise for TCR repertoire analyses. TCR repertoires in Vgamma2Vdelta2 T-cell subpopulation were broad during primary Mtb infection as most TCR clones found in lymphoid system, lung, kidney and liver were distinct. Polyclonally-expanded Vgamma2Vdelta2 T-cell clones from lymphoid tissues appeared to distribute and localize in lung TB granuloms at the endpoint after Mtb infection by aerosol. Interestingly, some TCR clones appeared to be more predominant than others in lymphocytes from liver or kidney without apparent TB lesions. TCR CDR3 spetratyping revealed such clonal dominance, and the clonal dominance of expanded Vgamma2Vdelta2 T cells in kidney/liver tissues was associated with undetectable or low-level TB burdens. Furthermore, Vgamma2Vdelta2 T cells from tissue compartments could mount effector function for producing anti-mycobacterium cytokine. CONCLUSION: We were the first to demonstrate clonal immune responses of mycobacterium-specific Vgamma2Vdelta2 T cells in the lymphoid system, heavily infected lungs and lately subtly-infected kidneys or livers during primary Mtb infection. While clonally-expanded Vgamma2Vdelta2 T cells accumulated in lately infected kidneys/livers without apparent TB lesions, TB burdens or lesions appeared to impact TCR repertoires and tissue trafficking patterns of activated Vgamma2Vdelta2 T cells. PMID- 22319575 TI - Activation and inhibition of transglutaminase 2 in mice. AB - Transglutaminase 2 (TG2) is an allosterically regulated enzyme with transamidating, deamidating and cell signaling activities. It is thought to catalyze sequence-specific deamidation of dietary gluten peptides in the small intestines of celiac disease patients. Because this modification has profound consequences for disease pathogenesis, there is considerable interest in the design of small molecule TG2 inhibitors. Although many classes of TG2 inhibitors have been reported, thus far an animal model for screening them to identify promising celiac drug candidates has remained elusive. Using intraperitoneal administration of the toll-like receptor 3 (TLR3) ligand, polyinosinic polycytidylic acid (poly(I?C)), we induced rapid TG2 activation in the mouse small intestine. Dose dependence was observed in the activation of TG2 as well as the associated villous atrophy, gross clinical response, and rise in serum concentration of the IL-15/IL-15R complex. TG2 activity was most pronounced in the upper small intestine. No evidence of TG2 activation was observed in the lung mucosa, nor were TLR7/8 ligands able to elicit an analogous response. Introduction of ERW1041E, a small molecule TG2 inhibitor, in this mouse model resulted in TG2 inhibition in the small intestine. TG2 inhibition had no effect on villous atrophy, suggesting that activation of this enzyme is a consequence, rather than a cause, of poly(I?C) induced enteropathy. Consistent with this finding, administration of poly(I?C) to TG2 knockout mice also induced villous atrophy. Our findings pave the way for pharmacological evaluation of small molecule TG2 inhibitors as drug candidates for celiac disease. PMID- 22319576 TI - Four waves of hepatocyte proliferation linked with three waves of hepatic fat accumulation during partial hepatectomy-induced liver regeneration. AB - Partial hepatectomy (PH) triggers hepatocyte proliferation-mediated liver repair and is widely used to study the mechanisms governing liver regeneration in mice. However, the dynamics of the hepatocyte proliferative response to PH remain unclear. We found that PH-induced mouse liver regrowth was driven by four consecutive waves of hepatocyte replication. The first wave exhibited the highest magnitude followed by two moderate waves and one minor wave. Underlying this continuous hepatocyte replication was persistent activation of cell cycle components throughout the period of liver regeneration. Hepatocyte mitotic activity in the first three proliferative cycles showed a circadian rhythm manifested by three corresponding mitosis peaks, which were always observed at Zeitgeber time 0. The Bmal1-Clock/Wee1/Cdc2 pathway has been proposed by others to govern the circadian rhythm of hepatocyte mitosis during liver regeneration. However, we did not observe the correlations in the expression or phosphorylation of these proteins in regenerating livers. Notably, Bmal1 protein displayed frequent changes in hepatic distribution and cellular localization as the liver regrowth progressed. Further, three waves of hepatic fat accumulation occurred during hepatic regeneration. The first started before and lasted through the first round of hepatocyte proliferation, whereas the second and third occurred concomitantly with the second and third mitotic peaks, respectively. CONCLUSION: PH-induced liver regeneration consists of four continuous waves of hepatocyte proliferation coupled with three waves of hepatic fat accumulation. Bmal1, Wee1, and Cdc2 may not form a pathway regulating the circadian rhythm of hepatocyte mitosis during liver regeneration. PMID- 22319577 TI - Accumulation of CCR4+CTLA-4 FOXP3+CD25(hi) regulatory T cells in colon adenocarcinomas correlate to reduced activation of conventional T cells. AB - BACKGROUND: Colorectal cancer usually gives rise to a specific anti-tumor immune response, but for unknown reasons the resulting immunity is not able to clear the tumor. Recruitment of activated effector lymphocytes to the tumor is important for efficient anti-tumor responses, while the presence of regulatory T cells (Treg) down-modulate tumor-specific immunity. We therefore aimed to determine homing mechanisms and activation stage of Treg and effector T cell infiltrating colon tumors compared to cells from the unaffected mucosa in patients suffering from colon adenocarcinoma. METHODOLOGY/PRINCIPAL FINDINGS: Lymphocytes were isolated from unaffected and tumor mucosa from patients with colon adenocarcinoma, and flow cytometry, immunohistochemistry, and quantitative PCR was used to investigate the homing mechanisms and activation stage of infiltrating Treg and conventional lymphocytes. We detected significantly higher frequencies of CD25(high)FOXP3+CD127(low) putative Treg in tumors than unaffected mucosa, which had a complete demethylation in the FOXP3 promotor. Tumor associated Treg had a high expression of CTLA-4, and some appeared to be antigen experienced effector/memory cells based on their expression of alphaEbeta7 (CD103). There were also significantly fewer activated T cells and more CTLA-4+ conventional T cells susceptible to immune regulation in the tumor-associated mucosa. In contrast, CD8+granzyme B+ putative cytotoxic cells were efficiently recruited to the tumors. The frequencies of cells expressing alpha4beta7 and the Th1 associated chemokine receptor CXCR3 were significantly decreased among CD4+ T cells in the tumor, while frequencies of CD4+CCR4+ lymphocytes were significantly increased. CONCLUSIONS/SIGNIFICANCE: This study shows that CCR4+CTLA4(hi) Treg accumulate in colon tumors, while the frequencies of activated conventional Th1 type T cells are decreased. The altered lymphocyte composition in colon tumors will probably diminish the ability of the immune system to effectively attack tumor cells, and reducing the Treg activity is an important challenge for future immunotherapy protocols. PMID- 22319578 TI - RDH10 oxidation of Vitamin A is a critical control step in synthesis of retinoic acid during mouse embryogenesis. AB - Retinoic Acid (RA) is a small lipophilic signaling molecule essential for embryonic development and adult tissue maintenance. Both an excess of RA and a deficiency of RA can cause pathogenic anomalies, hence it is critical to understand the mechanisms controlling the spatial and temporal distribution of RA. However, our current understanding of these processes remains incomplete. Vitamin A is metabolized to RA via two sequential enzymatic reactions. The first requires retinol dehydrogenase (RDH) activity to oxidize Vitamin A (retinol) to retinal, and the second requires retinaldehyde activity (RALDH) to oxidize retinal into RA. The first reaction has previously been attributed to the alcohol dehydrogenase (ADH) family, whose genes are ubiquitously or redundantly expressed. Consequently, the specificity of RA synthesis was thought to reside exclusively at the level of the second reaction. To better understand the metabolism of Vitamin A into RA during embryogenesis, we generated new mouse models that disrupt this process. Here we describe a new targeted knockout of Rdh10 in which RA synthesis is severely impaired, particularly at critical early embryonic stages. We also introduce a new mutant allele of Aldh1a2. Both mutations produce similar developmental defects resulting in lethality around embryonic day 10.5 (E10.5). The severity of the Rdh10 null phenotype demonstrates that embryonic oxidation of retinol is carried out primarily by RDH10 and that neither ADHs nor other enzymes contribute significantly to this reaction. We also show that reduced RA production results in upregulation of Rdh10. These data demonstrate that RDH10 plays a critical role in mediating the rate limiting RDH step of Vitamin A metabolism and functions as a nodal point in feedback regulation of RA synthesis. Moreover, RDH10-mediated oxidation of retinol plays as important a role in the control and regulation of RA production during embryogenesis as does the subsequent RALDH-mediated reaction. PMID- 22319579 TI - Ovotoxic effects of galactose involve attenuation of follicle-stimulating hormone bioactivity and up-regulation of granulosa cell p53 expression. AB - Clinical evidence suggests an association between galactosaemia and premature ovarian insufficiency (POI); however, the mechanism still remains unresolved. Experimental galactose toxicity in rats produces an array of ovarian dysfunction including ovarian development with deficient follicular reserve and follicular resistance to gonadotrophins that characterize the basic tenets of human POI. The present investigation explores if galactose toxicity in rats attenuates the bioactivity of gonadotrophins or interferes with their receptor competency, and accelerates the rate of follicular atresia. Pregnant rats were fed isocaloric food-pellets supplemented with or without 35% D-galactose from day-3 of gestation and continuing through weaning of the litters. The 35-day old female litters were autopsied. Serum galactose-binding capacity, galactosyltransferase (GalTase) activity, and bioactivity of FSH and LH together with their receptor competency were assessed. Ovarian follicular atresia was evaluated in situ by TUNEL. The in vitro effects of galactose were studied in isolated whole follicles in respect of generation of reactive oxygen species (ROS) and expression of caspase 3, and in isolated granulosa cells in respect of mitochondrial membrane potential, expression of p53, and apoptosis. The rats prenatally exposed to galactose exhibited significantly decreased serum GalTase activity and greater degree of galactose-incorporation capacity of sera proteins. LH biopotency and LH-FSH receptor competency were comparable between the control and study population, but the latter group showed significantly attenuated FSH bioactivity and increased rate of follicular atresia. In culture, galactose increased follicular generation of ROS and expression of caspase 3. In isolated granulosa cells, galactose disrupted mitochondrial membrane potential, stimulated p53 expression, and induced apoptosis in vitro; however co-treatment with either FSH or estradiol significantly prevented galactose-induced granulosa cell p53 expression. We conclude that the ovotoxic effects of galactose involves attenuation of FSH bioactivity that renders the ovary resistant to gonadotrophins leading to increased granulosa cell expression of p53 and follicular atresia. PMID- 22319580 TI - Routine antenatal anti-D prophylaxis in women who are Rh(D) negative: meta analyses adjusted for differences in study design and quality. AB - BACKGROUND: To estimate the effectiveness of routine antenatal anti-D prophylaxis for preventing sensitisation in pregnant Rhesus negative women, and to explore whether this depends on the treatment regimen adopted. METHODS: Ten studies identified in a previous systematic literature search were included. Potential sources of bias were systematically identified using bias checklists, and their impact and uncertainty were quantified using expert opinion. Study results were adjusted for biases and combined, first in a random-effects meta-analysis and then in a random-effects meta-regression analysis. RESULTS: In a conventional meta-analysis, the pooled odds ratio for sensitisation was estimated as 0.25 (95% CI 0.18, 0.36), comparing routine antenatal anti-D prophylaxis to control, with some heterogeneity (I2 = 19%). However, this naive analysis ignores substantial differences in study quality and design. After adjusting for these, the pooled odds ratio for sensitisation was estimated as 0.31 (95% CI 0.17, 0.56), with no evidence of heterogeneity (I2 = 0%). A meta-regression analysis was performed, which used the data available from the ten anti-D prophylaxis studies to inform us about the relative effectiveness of three licensed treatments. This gave an 83% probability that a dose of 1250 IU at 28 and 34 weeks is most effective and a 76% probability that a single dose of 1500 IU at 28-30 weeks is least effective. CONCLUSION: There is strong evidence for the effectiveness of routine antenatal anti-D prophylaxis for prevention of sensitisation, in support of the policy of offering routine prophylaxis to all non-sensitised pregnant Rhesus negative women. All three licensed dose regimens are expected to be effective. PMID- 22319581 TI - Interactions of adiponectin and lipopolysaccharide from Porphyromonas gingivalis on human oral epithelial cells. AB - BACKGROUND: Periodontitis is an inflammatory disease caused by pathogenic microorganisms, such as Porphyromonas gingivalis, and characterized by the destruction of the periodontium. Obese individuals have an increased risk for periodontitis and show decreased serum levels of adiponectin. This in-vitro study was established to examine whether adiponectin modulates critical effects of lipopolysaccharide (LPS) from P. gingivalis on oral epithelial cells (OECs). METHODOLOGY/PRINCIPAL FINDINGS: The presence of adiponectin and its receptors in human gingival tissue samples and OECs was analyzed by immunohistochemistry and PCR. Furthermore, OECs were treated with LPS and/or adiponectin for up to 72 h, and the gene expression and protein synthesis of pro- and anti-inflammatory mediators, matrix metalloproteinases (MMPs) and growth factors were analyzed by real-time PCR and ELISA. Additionally, cell proliferation, differentiation and in vitro wound healing were studied. The nuclear translocation of NFkappaB was investigated by immunofluorescence. Gingival tissue sections showed a strong synthesis of adiponectin and its receptors in the epithelial layer. In cell cultures, LPS induced a significant up-regulation of interleukin (IL) 1beta, IL6, IL8, MMP1 and MMP3. Adiponectin abrogated significantly the stimulatory effects of LPS on these molecules. Similarly, adiponectin inhibited significantly the LPS induced decrease in cell viability and increase in cell proliferation and differentiation. Adiponectin led to a time-dependent induction of the anti inflammatory mediators IL10 and heme oxygenase 1, and blocked the LPS-stimulated NFkappaB nuclear translocation. CONCLUSIONS/SIGNIFICANCE: Adiponectin may counteract critical actions of P. gingivalis on oral epithelial cells. Low levels of adiponectin, as observed in obese individuals, may increase the risk for periodontal inflammation and destruction. PMID- 22319582 TI - Diet and energy-sensing inputs affect TorC1-mediated axon misrouting but not TorC2-directed synapse growth in a Drosophila model of tuberous sclerosis. AB - The Target of Rapamycin (TOR) growth regulatory system is influenced by a number of different inputs, including growth factor signaling, nutrient availability, and cellular energy levels. While the effects of TOR on cell and organismal growth have been well characterized, this pathway also has profound effects on neural development and behavior. Hyperactivation of the TOR pathway by mutations in the upstream TOR inhibitors TSC1 (tuberous sclerosis complex 1) or TSC2 promotes benign tumors and neurological and behavioral deficits, a syndrome known as tuberous sclerosis (TS). In Drosophila, neuron-specific overexpression of Rheb, the direct downstream target inhibited by Tsc1/Tsc2, produced significant synapse overgrowth, axon misrouting, and phototaxis deficits. To understand how misregulation of Tor signaling affects neural and behavioral development, we examined the influence of growth factor, nutrient, and energy sensing inputs on these neurodevelopmental phenotypes. Neural expression of Pi3K, a principal mediator of growth factor inputs to Tor, caused synapse overgrowth similar to Rheb, but did not disrupt axon guidance or phototaxis. Dietary restriction rescued Rheb-mediated behavioral and axon guidance deficits, as did overexpression of AMPK, a component of the cellular energy sensing pathway, but neither was able to rescue synapse overgrowth. While axon guidance and behavioral phenotypes were affected by altering the function of a Tor complex 1 (TorC1) component, Raptor, or a TORC1 downstream element (S6k), synapse overgrowth was only suppressed by reducing the function of Tor complex 2 (TorC2) components (Rictor, Sin1). These findings demonstrate that different inputs to Tor signaling have distinct activities in nervous system development, and that Tor provides an important connection between nutrient-energy sensing systems and patterning of the nervous system. PMID- 22319583 TI - Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. AB - Most human pre-mRNAs are spliced into linear molecules that retain the exon order defined by the genomic sequence. By deep sequencing of RNA from a variety of normal and malignant human cells, we found RNA transcripts from many human genes in which the exons were arranged in a non-canonical order. Statistical estimates and biochemical assays provided strong evidence that a substantial fraction of the spliced transcripts from hundreds of genes are circular RNAs. Our results suggest that a non-canonical mode of RNA splicing, resulting in a circular RNA isoform, is a general feature of the gene expression program in human cells. PMID- 22319584 TI - Cupricyclins, novel redox-active metallopeptides based on conotoxins scaffold. AB - Highly stable natural scaffolds which tolerate multiple amino acid substitutions represent the ideal starting point for the application of rational redesign strategies to develop new catalysts of potential biomedical and biotechnological interest. The knottins family of disulphide-constrained peptides display the desired characteristics, being highly stable and characterized by hypervariability of the inter-cysteine loops. The potential of knottins as scaffolds for the design of novel copper-based biocatalysts has been tested by engineering a metal binding site on two different variants of an omega-conotoxin, a neurotoxic peptide belonging to the knottins family. The binding site has been designed by computational modelling and the redesigned peptides have been synthesized and characterized by optical, fluorescence, electron spin resonance and nuclear magnetic resonance spectroscopy. The novel peptides, named Cupricyclin-1 and -2, bind one Cu(2+) ion per molecule with nanomolar affinity. Cupricyclins display redox activity and catalyze the dismutation of superoxide anions with an activity comparable to that of non-peptidic superoxide dismutase mimics. We thus propose knottins as a novel scaffold for the design of catalytically-active mini metalloproteins. PMID- 22319585 TI - Successful shortening of tuberculosis treatment using adjuvant host-directed therapy with FDA-approved phosphodiesterase inhibitors in the mouse model. AB - Global control of tuberculosis (TB), an infectious disease that claims nearly 2 million lives annually, is hindered by the long duration of chemotherapy required for curative treatment. Lack of adherence to this intense treatment regimen leads to poor patient outcomes, development of new or additional drug resistance, and continued spread of M.tb. within communities. Hence, shortening the duration of TB therapy could increase drug adherence and cure in TB patients. Here, we report that addition of the United Stated Food and Drug Administration-approved phosphodiesterase inhibitors (PDE-Is) cilostazol and sildenafil to the standard TB treatment regimen reduces tissue pathology, leads to faster bacterial clearance and shortens the time to lung sterilization by one month, compared to standard treatment alone, in a murine model of TB. Our data suggest that these PDE-Is could be repurposed for use as adjunctive drugs to shorten TB treatment in humans. PMID- 22319586 TI - The integrative effects of cognitive reappraisal on negative affect: associated changes in secretory immunoglobulin A, unpleasantness and ERP activity. AB - Although the regulatory role of cognitive reappraisal in negative emotional responses is widely recognized, this reappraisal's effect on acute saliva secretory immunoglobulin A (SIgA), as well as the relationships among affective, immunological, and event-related potential (ERP) changes, remains unclear. In this study, we selected only people with low positive coping scores (PCSs) as measured by the Trait Coping Style Questionnaire to avoid confounding by intrinsic coping styles. First, we found that the acute stress of viewing unpleasant pictures consistently decreased SIgA concentration and secretion rate, increased perceptions of unpleasantness and amplitude of late positive potentials (LPPs) between 200-300 ms and 400-1000 ms. After participants used cognitive reappraisal, their SIgA concentration and secretion rate significantly increased and their unpleasantness and LPP amplitudes significantly decreased compared with a control condition. Second, we found a significantly positive correlation between the increases in SIgA and the decreases in unpleasantness and a significantly negative correlation between the increases in SIgA and the increases in LPP across the two groups. This study is the first to demonstrate that cognitive reappraisal reverses the decrease of SIgA. In addition, it revealed strong correlations among affective, SIgA and electrophysiological changes with convergent multilevel evidence. PMID- 22319587 TI - CCL2-expressing astrocytes mediate the extravasation of T lymphocytes in the brain. Evidence from patients with glioma and experimental models in vivo. AB - CCL2 is a chemokine involved in brain inflammation, but the way in which it contributes to the entrance of lymphocytes in the parenchyma is unclear. Imaging of the cell type responsible for this task and details on how the process takes place in vivo remain elusive. Herein, we analyze the cell type that overexpresses CCL2 in multiple scenarios of T-cell infiltration in the brain and in three different species. We observe that CCL2+ astrocytes play a part in the infiltration of T-cells in the brain and our analysis shows that the contact of T cells with perivascular astrocytes occurs, suggesting that may be an important event for lymphocyte extravasation. PMID- 22319588 TI - Influence of milk-feeding type and genetic risk of developing coeliac disease on intestinal microbiota of infants: the PROFICEL study. AB - Interactions between environmental factors and predisposing genes could be involved in the development of coeliac disease (CD). This study has assessed whether milk-feeding type and HLA-genotype influence the intestinal microbiota composition of infants with a family history of CD. The study included 164 healthy newborns, with at least one first-degree relative with CD, classified according to their HLA-DQ genotype by PCR-SSP DQB1 and DQA1 typing. Faecal microbiota was analysed by quantitative PCR at 7 days, and at 1 and 4 months of age. Significant interactions between milk-feeding type and HLA-DQ genotype on bacterial numbers were not detected by applying a linear mixed-model analysis for repeated measures. In the whole population, breast-feeding promoted colonization of C. leptum group, B. longum and B. breve, while formula-feeding promoted that of Bacteroides fragilis group, C. coccoides-E. rectale group, E. coli and B. lactis. Moreover, increased numbers of B. fragilis group and Staphylococcus spp., and reduced numbers of Bifidobacterium spp. and B. longum were detected in infants with increased genetic risk of developing CD. Analyses within subgroups of either breast-fed or formula-fed infants indicated that in both cases increased risk of CD was associated with lower numbers of B. longum and/or Bifidobacterium spp. In addition, in breast-fed infants the increased genetic risk of developing CD was associated with increased C. leptum group numbers, while in formula-fed infants it was associated with increased Staphylococcus and B. fragilis group numbers. Overall, milk-feeding type in conjunction with HLA-DQ genotype play a role in establishing infants' gut microbiota; moreover, breast feeding reduced the genotype-related differences in microbiota composition, which could partly explain the protective role attributed to breast milk in this disorder. PMID- 22319589 TI - Parallel evolution under chemotherapy pressure in 29 breast cancer cell lines results in dissimilar mechanisms of resistance. AB - BACKGROUND: Developing chemotherapy resistant cell lines can help to identify markers of resistance. Instead of using a panel of highly heterogeneous cell lines, we assumed that truly robust and convergent pattern of resistance can be identified in multiple parallel engineered derivatives of only a few parental cell lines. METHODS: Parallel cell populations were initiated for two breast cancer cell lines (MDA-MB-231 and MCF-7) and these were treated independently for 18 months with doxorubicin or paclitaxel. IC50 values against 4 chemotherapy agents were determined to measure cross-resistance. Chromosomal instability and karyotypic changes were determined by cytogenetics. TaqMan RT-PCR measurements were performed for resistance-candidate genes. Pgp activity was measured by FACS. RESULTS: All together 16 doxorubicin- and 13 paclitaxel-treated cell lines were developed showing 2-46 fold and 3-28 fold increase in resistance, respectively. The RT-PCR and FACS analyses confirmed changes in tubulin isofom composition, TOP2A and MVP expression and activity of transport pumps (ABCB1, ABCG2). Cytogenetics showed less chromosomes but more structural aberrations in the resistant cells. CONCLUSION: We surpassed previous studies by parallel developing a massive number of cell lines to investigate chemoresistance. While the heterogeneity caused evolution of multiple resistant clones with different resistance characteristics, the activation of only a few mechanisms were sufficient in one cell line to achieve resistance. PMID- 22319590 TI - STAT3 is activated by JAK2 independent of key oncogenic driver mutations in non small cell lung carcinoma. AB - Constitutive activation of STAT3 is a common feature in many solid tumors including non-small cell lung carcinoma (NSCLC). While activation of STAT3 is commonly achieved by somatic mutations to JAK2 in hematologic malignancies, similar mutations are not often found in solid tumors. Previous work has instead suggested that STAT3 activation in solid tumors is more commonly induced by hyperactive growth factor receptors or autocrine cytokine signaling. The interplay between STAT3 activation and other well-characterized oncogenic "driver" mutations in NSCLC has not been fully characterized, though constitutive STAT3 activation has been proposed to play an important role in resistance to various small-molecule therapies that target these oncogenes. In this study we demonstrate that STAT3 is constitutively activated in human NSCLC samples and in a variety of NSCLC lines independent of activating KRAS or tyrosine kinase mutations. We further show that genetic or pharmacologic inhibition of the gp130/JAK2 signaling pathway disrupts activation of STAT3. Interestingly, treatment of NSCLC cells with the JAK1/2 inhibitor ruxolitinib has no effect on cell proliferation and viability in two-dimensional culture, but inhibits growth in soft agar and xenograft assays. These data demonstrate that JAK2/STAT3 signaling operates independent of known driver mutations in NSCLC and plays critical roles in tumor cell behavior that may not be effectively inhibited by drugs that selectively target these driver mutations. PMID- 22319591 TI - Transcriptional analysis of Shewanella oneidensis MR-1 with an electrode compared to Fe(III)citrate or oxygen as terminal electron acceptor. AB - Shewanella oneidensis is a target of extensive research in the fields of bioelectrochemical systems and bioremediation because of its versatile metabolic capabilities, especially with regard to respiration with extracellular electron acceptors. The physiological activity of S. oneidensis to respire at electrodes is of great interest, but the growth conditions in thin-layer biofilms make physiological analyses experimentally challenging. Here, we took a global approach to evaluate physiological activity with an electrode as terminal electron acceptor for the generation of electric current. We performed expression analysis with DNA microarrays to compare the overall gene expression with an electrode to that with soluble iron(III) or oxygen as the electron acceptor and applied new hierarchical model-based statistics for the differential expression analysis. We confirmed the differential expression of many genes that have previously been reported to be involved in electrode respiration, such as the entire mtr operon. We also formulate hypotheses on other possible gene involvements in electrode respiration, for example, a role of ScyA in inter protein electron transfer and a regulatory role of the cbb3-type cytochrome c oxidase under anaerobic conditions. Further, we hypothesize that electrode respiration imposes a significant stress on S. oneidensis, resulting in higher energetic costs for electrode respiration than for soluble iron(III) respiration, which fosters a higher metabolic turnover to cover energy needs. Our hypotheses now require experimental verification, but this expression analysis provides a fundamental platform for further studies into the molecular mechanisms of S. oneidensis electron transfer and the physiologically special situation of growth on a poised-potential surface. PMID- 22319592 TI - Noradrenergic alpha1 receptor antagonist treatment attenuates positive subjective effects of cocaine in humans: a randomized trial. AB - BACKGROUND: Preclinical research implicates dopaminergic and noradrenergic mechanisms in mediating the reinforcing effects of drugs of abuse, including cocaine. The objective of this study was to evaluate the impact of treatment with the noradrenergic alpha(1) receptor antagonist doxazosin on the positive subjective effects of cocaine. METHODS: Thirteen non-treatment seeking, cocaine dependent volunteers completed this single-site, randomized, placebo-controlled, within-subjects study. In one study phase volunteers received placebo and in the other they received doxazosin, with the order counterbalanced across participants. Study medication was masked by over-encapsulating doxazosin tablets and matched placebo lactose served as the control. Study medication treatment was initiated at 1 mg doxazosin or equivalent number of placebo capsules PO/day and increased every three days by 1 mg. After receiving 4 mg doxazosin or equivalent number of placebo capsules participants received masked doses of 20 and 40 mg cocaine IV in that order with placebo saline randomly interspersed to maintain the blind. RESULTS: Doxazosin treatment was well tolerated and doxazosin alone produced minimal changes in heart rate and blood pressure. During treatment with placebo, cocaine produced dose-dependent increases in subjective effect ratings of "high", "stimulated", "like cocaine", "desire cocaine", "any drug effect", and "likely to use cocaine if had access" (p<.001). Doxazosin treatment significantly attenuated the effects of 20 mg cocaine on ratings of "stimulated", "like cocaine", and "likely to use cocaine if had access" (p<.05). There were trends for doxazosin to reduce ratings of "stimulated", "desire cocaine", and "likely to use cocaine if had access" (p<.10). CONCLUSIONS: Medications that block noradrenergic alpha1 receptors, such as doxazosin, may be useful as treatments for cocaine dependence, and should be evaluated further. TRIAL REGISTRATION: Clinicaltrials.gov NCT01062945. PMID- 22319593 TI - Introspective minds: using ALE meta-analyses to study commonalities in the neural correlates of emotional processing, social & unconstrained cognition. AB - Previous research suggests overlap between brain regions that show task-induced deactivations and those activated during the performance of social-cognitive tasks. Here, we present results of quantitative meta-analyses of neuroimaging studies, which confirm a statistical convergence in the neural correlates of social and resting state cognition. Based on the idea that both social and unconstrained cognition might be characterized by introspective processes, which are also thought to be highly relevant for emotional experiences, a third meta analysis was performed investigating studies on emotional processing. By using conjunction analyses across all three sets of studies, we can demonstrate significant overlap of task-related signal change in dorso-medial prefrontal and medial parietal cortex, brain regions that have, indeed, recently been linked to introspective abilities. Our findings, therefore, provide evidence for the existence of a core neural network, which shows task-related signal change during socio-emotional tasks and during resting states. PMID- 22319594 TI - Benzo[a]pyrene, aflatoxine B1 and acetaldehyde mutational patterns in TP53 gene using a functional assay: relevance to human cancer aetiology. AB - Mutations in the TP53 gene are the most common alterations in human tumours. TP53 mutational patterns have sometimes been linked to carcinogen exposure. In hepatocellular carcinoma, a specific G>T transversion on codon 249 is classically described as a fingerprint of aflatoxin B(1) exposure. Likewise G>T transversions in codons 157 and 158 have been related to tobacco exposure in human lung cancers. However, controversies remain about the interpretation of TP53 mutational pattern in tumours as the fingerprint of genotoxin exposure. By using a functional assay, the Functional Analysis of Separated Alleles in Yeast (FASAY), the present study depicts the mutational pattern of TP53 in normal human fibroblasts after in vitro exposure to well-known carcinogens: benzo[a]pyrene, aflatoxin B(1) and acetaldehyde. These in vitro patterns of mutations were then compared to those found in human tumours by using the IARC database of TP53 mutations. The results show that the TP53 mutational patterns found in human tumours can be only partly ascribed to genotoxin exposure. A complex interplay between the functional impact of the mutations on p53 phenotype and the cancer natural history may affect these patterns. However, our results strongly support that genotoxins exposure plays a major role in the aetiology of the considered cancers. PMID- 22319595 TI - Defining early human NK cell developmental stages in primary and secondary lymphoid tissues. AB - A better understanding of human NK cell development in vivo is crucial to exploit NK cells for immunotherapy. Here, we identified seven distinctive NK cell developmental stages in bone marrow of single donors using 10-color flow cytometry and found that NK cell development is accompanied by early expression of stimulatory co-receptor CD244 in vivo. Further analysis of cord blood (CB), peripheral blood (PB), inguinal lymph node (inLN), liver lymph node (liLN) and spleen (SPL) samples showed diverse distributions of the NK cell developmental stages. In addition, distinctive expression profiles of early development marker CD33 and C-type lectin receptor NKG2A between the tissues, suggest that differential NK cell differentiation may take place at different anatomical locations. Differential expression of NKG2A and stimulatory receptors (e.g. NCR, NKG2D) within the different subsets of committed NK cells demonstrated the heterogeneity of the CD56(bright)CD16+/- and CD56(dim)CD16+ subsets within the different compartments and suggests that microenvironment may play a role in differential in situ development of the NK cell receptor repertoire of committed NK cells. Overall, differential in situ NK cell development and trafficking towards multiple tissues may give rise to a broad spectrum of mature NK cell subsets found within the human body. PMID- 22319596 TI - Travel to school and physical activity levels in 9-10 year-old UK children of different ethnic origin; Child Heart and Health Study in England (CHASE). AB - BACKGROUND: Travel to school may offer a convenient way to increase physical activity levels in childhood. We examined the association between method of travel to school and physical activity levels in urban multi-ethnic children. METHODS AND FINDINGS: 2035 children (aged 9-10 years in 2006-7) provided data on their usual method of travel to school and wore an Actigraph-GT1M activity monitor during waking hours. Associations between method of travel and mean level of physical activity (counts per minute [CPM], steps, time spent in light, moderate or vigorous activity per day) were examined in models adjusted for confounding variables. 1393 children (69%) walked or cycled to school; 161 (8%) used public transport and 481 (24%) travelled by car. White European children were more likely to walk/cycle, black African Caribbeans to travel by public transport and South Asian children to travel by car. Children travelling by car spent less time in moderate to vigorous physical activity (-7 mins, 95%CI-9,-5), and had lower CPM (-32 CPM, 95%CI-44,-19) and steps per day (-813 steps, 95%CI, 1043,-582) than walkers/cyclists. Pupils travelling by public transport had similar activity levels to walkers/cyclists. Lower physical activity levels amongst car travellers' were especially marked at travelling times (school days between 8-9 am, 3-5 pm), but were also evident on weekdays at other times and at weekends; they did not differ by gender or ethnic group. CONCLUSION: Active travel to school is associated with higher levels of objectively measured physical activity, particularly during periods of travel but also at other times. If children travelling by car were to achieve physical activity levels (steps) similar to children using active travel, they would increase their physical activity levels by 9%. However, the population increase would be a modest 2%, because of the low proportion of car travellers in this urban population. PMID- 22319597 TI - Complexity of murine cardiomyocyte miRNA biogenesis, sequence variant expression and function. AB - microRNAs (miRNAs) are critical to heart development and disease. Emerging research indicates that regulated precursor processing can give rise to an unexpected diversity of miRNA variants. We subjected small RNA from murine HL-1 cardiomyocyte cells to next generation sequencing to investigate the relevance of such diversity to cardiac biology. ~40 million tags were mapped to known miRNA hairpin sequences as deposited in miRBase version 16, calling 403 generic miRNAs as appreciably expressed. Hairpin arm bias broadly agreed with miRBase annotation, although 44 miR* were unexpectedly abundant (>20% of tags); conversely, 33 -5p/-3p annotated hairpins were asymmetrically expressed. Overall, variability was infrequent at the 5' start but common at the 3' end of miRNAs (5.2% and 52.3% of tags, respectively). Nevertheless, 105 miRNAs showed marked 5' isomiR expression (>20% of tags). Among these was miR-133a, a miRNA with important cardiac functions, and we demonstrated differential mRNA targeting by two of its prevalent 5' isomiRs. Analyses of miRNA termini and base-pairing patterns around Drosha and Dicer cleavage regions confirmed the known bias towards uridine at the 5' most position of miRNAs, as well as supporting the thermodynamic asymmetry rule for miRNA strand selection and a role for local structural distortions in fine tuning miRNA processing. We further recorded appreciable expression of 5 novel miR*, 38 extreme variants and 8 antisense miRNAs. Analysis of genome-mapped tags revealed 147 novel candidate miRNAs. In summary, we revealed pronounced sequence diversity among cardiomyocyte miRNAs, knowledge of which will underpin future research into the mechanisms involved in miRNA biogenesis and, importantly, cardiac function, disease and therapy. PMID- 22319598 TI - Acute beneficial hemodynamic effects of a novel 3D-echocardiographic optimization protocol in cardiac resynchronization therapy. AB - BACKGROUND: Post-implantation therapies to optimize cardiac resynchronization therapy (CRT) focus on adjustments of the atrio-ventricular (AV) delay and ventricular-to-ventricular (VV) interval. However, there is little consensus on how to achieve best resynchronization with these parameters. The aim of this study was to examine a novel combination of doppler echocardiography (DE) and three-dimensional echocardiography (3DE) for individualized optimization of device based AV delays and VV intervals compared to empiric programming. METHODS: 25 recipients of CRT (male: 56%, mean age: 67 years) were included in this study. Ejection fraction (EF), the primary outcome parameter, and left ventricular (LV) dimensions were evaluated by 3DE before CRT (baseline), after AV delay optimization while pacing the ventricles simultaneously (empiric VV interval programming) and after individualized VV interval optimization. For AV delay optimization aortic velocity time integral (AoVTI) was examined in eight different AV delays, and the AV delay with the highest AoVTI was programmed. For individualized VV interval optimization 3DE full-volume datasets of the left ventricle were obtained and analyzed to derive a systolic dyssynchrony index (SDI), calculated from the dispersion of time to minimal regional volume for all 16 LV segments. Consecutively, SDI was evaluated in six different VV intervals (including LV or right ventricular preactivation), and the VV interval with the lowest SDI was programmed (individualized optimization). RESULTS: EF increased from baseline 23+/-7% to 30+/-8 (p<0.001) after AV delay optimization and to 32+/ 8% (p<0.05) after individualized optimization with an associated decrease of end systolic volume from a baseline of 138+/-60 ml to 115+/-42 ml (p<0.001). Moreover, individualized optimization significantly reduced SDI from a baseline of 14.3+/-5.5% to 6.1+/-2.6% (p<0.001). CONCLUSIONS: Compared with empiric programming of biventricular pacemakers, individualized echocardiographic optimization with the integration of 3-dimensional indices into the optimization protocol acutely improved LV systolic function and decreased ESV and can be used to select the optimal AV delay and VV interval in CRT. PMID- 22319599 TI - Feature-by-feature--evaluating de novo sequence assembly. AB - The whole-genome sequence assembly (WGSA) problem is among one of the most studied problems in computational biology. Despite the availability of a plethora of tools (i.e., assemblers), all claiming to have solved the WGSA problem, little has been done to systematically compare their accuracy and power. Traditional methods rely on standard metrics and read simulation: while on the one hand, metrics like N50 and number of contigs focus only on size without proportionately emphasizing the information about the correctness of the assembly, comparisons performed on simulated dataset, on the other hand, can be highly biased by the non-realistic assumptions in the underlying read generator. Recently the Feature Response Curve (FRC) method was proposed to assess the overall assembly quality and correctness: FRC transparently captures the trade-offs between contigs' quality against their sizes. Nevertheless, the relationship among the different features and their relative importance remains unknown. In particular, FRC cannot account for the correlation among the different features. We analyzed the correlation among different features in order to better describe their relationships and their importance in gauging assembly quality and correctness. In particular, using multivariate techniques like principal and independent component analysis we were able to estimate the "excess-dimensionality" of the feature space. Moreover, principal component analysis allowed us to show how poorly the acclaimed N50 metric describes the assembly quality. Applying independent component analysis we identified a subset of features that better describe the assemblers performances. We demonstrated that by focusing on a reduced set of highly informative features we can use the FRC curve to better describe and compare the performances of different assemblers. Moreover, as a by product of our analysis, we discovered how often evaluation based on simulated data, obtained with state of the art simulators, lead to not-so-realistic results. PMID- 22319600 TI - Identification of anti-malarial compounds as novel antagonists to chemokine receptor CXCR4 in pancreatic cancer cells. AB - Despite recent advances in targeted therapies, patients with pancreatic adenocarcinoma continue to have poor survival highlighting the urgency to identify novel therapeutic targets. Our previous investigations have implicated chemokine receptor CXCR4 and its selective ligand CXCL12 in the pathogenesis and progression of pancreatic intraepithelial neoplasia and invasive pancreatic cancer; hence, CXCR4 is a promising target for suppression of pancreatic cancer growth. Here, we combined in silico structural modeling of CXCR4 to screen for candidate anti-CXCR4 compounds with in vitro cell line assays and identified NSC56612 from the National Cancer Institute's (NCI) Open Chemical Repository Collection as an inhibitor of activated CXCR4. Next, we identified that NSC56612 is structurally similar to the established anti-malarial drugs chloroquine and hydroxychloroquine. We evaluated these compounds in pancreatic cancer cells in vitro and observed specific antagonism of CXCR4-mediated signaling and cell proliferation. Recent in vivo therapeutic applications of chloroquine in pancreatic cancer mouse models have demonstrated decreased tumor growth and improved survival. Our results thus provide a molecular target and basis for further evaluation of chloroquine and hydroxychloroquine in pancreatic cancer. Historically safe in humans, chloroquine and hydroxychloroquine appear to be promising agents to safely and effectively target CXCR4 in patients with pancreatic cancer. PMID- 22319601 TI - Endogenous urotensin II selectively modulates erectile function through eNOS. AB - BACKGROUND: Urotensin II (U-II) is a cyclic peptide originally isolated from the neurosecretory system of the teleost fish and subsequently found in other species, including man. U-II was identified as the natural ligand of a G-protein coupled receptor, namely UT receptor. U-II and UT receptor are expressed in a variety of peripheral organs and especially in cardiovascular tissue. Recent evidence indicates the involvement of U-II/UT pathway in penile function in human, but the molecular mechanism is still unclear. On these bases the aim of this study is to investigate the mechanism(s) of U-II-induced relaxation in human corpus cavernosum and its relationship with L-arginine/Nitric oxide (NO) pathway. METHODOLOGY/PRINCIPAL FINDINGS: Human corpus cavernosum tissue was obtained following in male-to-female transsexuals undergoing surgical procedure for sex reassignment. Quantitative RT-PCR clearly demonstrated the U-II expression in human corpus cavernosum. U-II (0.1 nM-10 uM) challenge in human corpus cavernosum induced a significant increase in NO production as revealed by fluorometric analysis. NO generation was coupled to a marked increase in the ratio eNOS phosphorilated/eNOS as determined by western blot analysis. A functional study in human corpus cavernosum strips was performed to asses eNOS involvement in U-II induced relaxation by using a pharmacological modulation. Pre-treatment with both wortmannin or geldanamycinin (inhibitors of eNOS phosphorylation and heath shock protein 90 recruitment, respectively) significantly reduced U-II-induced relaxation (0.1 nM-10 uM) in human corpus cavernosum strips. Finally, a co immunoprecipitation study demonstrated that UT receptor and eNOS co immunoprecipitate following U-II challenge of human corpus cavernosum tissue. CONCLUSION/SIGNIFICANCE: U-II is endogenously synthesized and locally released in human corpus cavernosum. U-II elicited penile erection through eNOS activation. Thus, U-II/UT pathway may represent a novel therapeutical target in erectile dysfunction. PMID- 22319602 TI - A miR-1207-5p binding site polymorphism abolishes regulation of HBEGF and is associated with disease severity in CFHR5 nephropathy. AB - Heparin binding epidermal growth factor (HBEGF) is expressed in podocytes and was shown to play a role in glomerular physiology. MicroRNA binding sites on the 3'UTR of HBEGF were predicted using miRWalk algorithm and followed by DNA sequencing in 103 patients diagnosed with mild or severe glomerulopathy. A single nucleotide polymorphism, miRSNP C1936T (rs13385), was identified at the 3'UTR of HBEGF that corresponds to the second base of the hsa-miR-1207-5p seed region. When AB8/13 undifferentiated podocytes were transfected with miRNA mimics of hsa miR-1207-5p, the HBEGF protein levels were reduced by about 50%. A DNA fragment containing the miRSNP allele-1936C was cloned into the pMIR-Report Luciferase vector and co-transfected with miRNA mimics of hsa-miR-1207-5p into AB8/13 podocytes. In agreement with western blot data, this resulted in reduced luciferase expression demonstrating the ability of hsa-miR-1207-5p to directly regulate HBEGF expression. On the contrary, in the presence of the miRSNP 1936T allele, this regulation was abolished. Collectively, these results demonstrate that variant 1936T of this miRSNP prevents hsa-miR-1207-5p from down-regulating HBEGF in podocytes. We hypothesized that this variant has a functional role as a genetic modifier. To this end, we showed that in a cohort of 78 patients diagnosed with CFHR5 nephropathy (also known as C3-glomerulopathy), inheritance of miRSNP 1936T allele was significantly increased in the group demonstrating progression to chronic renal failure on long follow-up. No similar association was detected in a cohort of patients with thin basement membrane nephropathy. This is the first report associating a miRSNP as genetic modifier to a monogenic renal disorder. PMID- 22319603 TI - Ecologically appropriate xenobiotics induce cytochrome P450s in Apis mellifera. AB - BACKGROUND: Honey bees are exposed to phytochemicals through the nectar, pollen and propolis consumed to sustain the colony. They may also encounter mycotoxins produced by Aspergillus fungi infesting pollen in beebread. Moreover, bees are exposed to agricultural pesticides, particularly in-hive acaricides used against the parasite Varroa destructor. They cope with these and other xenobiotics primarily through enzymatic detoxificative processes, but the regulation of detoxificative enzymes in honey bees remains largely unexplored. METHODOLOGY/PRINCIPAL FINDINGS: We used several approaches to ascertain effects of dietary toxins on bee susceptibility to synthetic and natural xenobiotics, including the acaricide tau-fluvalinate, the agricultural pesticide imidacloprid, and the naturally occurring mycotoxin aflatoxin. We administered potential inducers of cytochrome P450 enzymes, the principal biochemical system for Phase 1 detoxification in insects, to investigate how detoxification is regulated. The drug phenobarbital induces P450s in many insects, yet feeding bees with phenobarbital had no effect on the toxicity of tau-fluvalinate, a pesticide known to be detoxified by bee P450s. Similarly, no P450 induction, as measured by tau fluvalinate tolerance, occurred in bees fed xanthotoxin, salicylic acid, or indole-3-carbinol, all of which induce P450s in other insects. Only quercetin, a common pollen and honey constituent, reduced tau-fluvalinate toxicity. In microarray comparisons no change in detoxificative gene expression was detected in phenobarbital-treated bees. However, northern blot analyses of guts of bees fed extracts of honey, pollen and propolis showed elevated expression of three CYP6AS P450 genes. Diet did not influence tau-fluvalinate or imidacloprid toxicity in bioassays; however, aflatoxin toxicity was higher in bees consuming sucrose or high-fructose corn syrup than in bees consuming honey. CONCLUSIONS/SIGNIFICANCE: These results suggest that regulation of honey bee P450s is tuned to chemicals occurring naturally in the hive environment and that, in terms of toxicological capacity, a diet of sugar is not equivalent to a diet of honey. PMID- 22319604 TI - Dorsal striatum and its limbic connectivity mediate abnormal anticipatory reward processing in obesity. AB - Obesity is characterized by an imbalance in the brain circuits promoting reward seeking and those governing cognitive control. Here we show that the dorsal caudate nucleus and its connections with amygdala, insula and prefrontal cortex contribute to abnormal reward processing in obesity. We measured regional brain glucose uptake in morbidly obese (n = 19) and normal weighted (n = 16) subjects with 2-[18F]fluoro-2-deoxyglucose ([18F]FDG) positron emission tomography (PET) during euglycemic hyperinsulinemia and with functional magnetic resonance imaging (fMRI) while anticipatory food reward was induced by repeated presentations of appetizing and bland food pictures. First, we found that glucose uptake rate in the dorsal caudate nucleus was higher in obese than in normal-weight subjects. Second, obese subjects showed increased hemodynamic responses in the caudate nucleus while viewing appetizing versus bland foods in fMRI. The caudate also showed elevated task-related functional connectivity with amygdala and insula in the obese versus normal-weight subjects. Finally, obese subjects had smaller responses to appetizing versus bland foods in the dorsolateral and orbitofrontal cortices than did normal-weight subjects, and failure to activate the dorsolateral prefrontal cortex was correlated with high glucose metabolism in the dorsal caudate nucleus. These findings suggest that enhanced sensitivity to external food cues in obesity may involve abnormal stimulus-response learning and incentive motivation subserved by the dorsal caudate nucleus, which in turn may be due to abnormally high input from the amygdala and insula and dysfunctional inhibitory control by the frontal cortical regions. These functional changes in the responsiveness and interconnectivity of the reward circuit could be a critical mechanism to explain overeating in obesity. PMID- 22319605 TI - The Pseudomonas aeruginosa transcriptome in planktonic cultures and static biofilms using RNA sequencing. AB - In this study, we evaluated how gene expression differs in mature Pseudomonas aeruginosa biofilms as opposed to planktonic cells by the use of RNA sequencing technology that gives rise to both quantitative and qualitative information on the transcriptome. Although a large proportion of genes were consistently regulated in both the stationary phase and biofilm cultures as opposed to the late exponential growth phase cultures, the global biofilm gene expression pattern was clearly distinct indicating that biofilms are not just surface attached cells in stationary phase. A large amount of the genes found to be biofilm specific were involved in adaptation to microaerophilic growth conditions, repression of type three secretion and production of extracellular matrix components. Additionally, we found many small RNAs to be differentially regulated most of them similarly in stationary phase cultures and biofilms. A qualitative analysis of the RNA-seq data revealed more than 3000 putative transcriptional start sites (TSS). By the use of rapid amplification of cDNA ends (5'-RACE) we confirmed the presence of three different TSS associated with the pqsABCDE operon, two in the promoter of pqsA and one upstream of the second gene, pqsB. Taken together, this study reports the first transcriptome study on P. aeruginosa that employs RNA sequencing technology and provides insights into the quantitative and qualitative transcriptome including the expression of small RNAs in P. aeruginosa biofilms. PMID- 22319606 TI - Start position strongly influences fixation patterns during face processing: difficulties with eye movements as a measure of information use. AB - Fixation patterns are thought to reflect cognitive processing and, thus, index the most informative stimulus features for task performance. During face recognition, initial fixations to the center of the nose have been taken to indicate this location is optimal for information extraction. However, the use of fixations as a marker for information use rests on the assumption that fixation patterns are predominantly determined by stimulus and task, despite the fact that fixations are also influenced by visuo-motor factors. Here, we tested the effect of starting position on fixation patterns during a face recognition task with upright and inverted faces. While we observed differences in fixations between upright and inverted faces, likely reflecting differences in cognitive processing, there was also a strong effect of start position. Over the first five saccades, fixation patterns across start positions were only coarsely similar, with most fixations around the eyes. Importantly, however, the precise fixation pattern was highly dependent on start position with a strong tendency toward facial features furthest from the start position. For example, the often-reported tendency toward the left over right eye was reversed for the left starting position. Further, delayed initial saccades for central versus peripheral start positions suggest greater information processing prior to the initial saccade, highlighting the experimental bias introduced by the commonly used center start position. Finally, the precise effect of face inversion on fixation patterns was also dependent on start position. These results demonstrate the importance of a non-stimulus, non-task factor in determining fixation patterns. The patterns observed likely reflect a complex combination of visuo-motor effects and simple sampling strategies as well as cognitive factors. These different factors are very difficult to tease apart and therefore great caution must be applied when interpreting absolute fixation locations as indicative of information use, particularly at a fine spatial scale. PMID- 22319607 TI - Yohimbine-induced amygdala activation in pathological gamblers: a pilot study. AB - RATIONALE AND OBJECTIVES: There is evidence that drug addiction is associated with increased physiological and psychological responses to stress. In this pilot functional magnetic resonance imaging (fMRI) study we assessed whether a prototype behavioral addiction, pathological gambling (PG), is likewise associated with an enhanced response to stress. METHODS: We induced stress by injecting yohimbine (0.2-0.3 mg/kg, IV), an alpha-2 adrenoceptor antagonist that elicits stress-like physiological and psychological effects in humans and in laboratory animals, to four subjects with PG and to five non-gamblers mentally healthy control subjects. Their fMRI brain responses were assessed along with subjective stress and gambling urges ratings. RESULTS: Voxelwise analyses of data sets from individual subjects, utilizing generalized linear model approach, revealed significant left amygdala activation in response to yohimbine across all PG subjects. This amygdala effect was not observed in the five control individuals. Yohimbine elicited subjective stress ratings in both groups with greater (albeit not statically significantly) average response in the PG subjects. On the other hand, yohimbine did not induce urges to gamble. CONCLUSIONS: The present data support the hypothesis of brain sensitization to pharmacologically-induced stress in PG. PMID- 22319608 TI - Visualization and quantitative analysis of reconstituted tight junctions using localization microscopy. AB - Tight Junctions (TJ) regulate paracellular permeability of tissue barriers. Claudins (Cld) form the backbone of TJ-strands. Pore-forming claudins determine the permeability for ions, whereas that for solutes and macromolecules is assumed to be crucially restricted by the strand morphology (i.e., density, branching and continuity). To investigate determinants of the morphology of TJ-strands we established a novel approach using localization microscopy.TJ-strands were reconstituted by stable transfection of HEK293 cells with the barrier-forming Cld3 or Cld5. Strands were investigated at cell-cell contacts by Spectral Position Determination Microscopy (SPDM), a method of localization microscopy using standard fluorophores. Extended TJ-networks of Cld3-YFP and Cld5-YFP were observed. For each network, 200,000 to 1,100,000 individual molecules were detected with a mean localization accuracy of ~20 nm, yielding a mean structural resolution of ~50 nm. Compared to conventional fluorescence microscopy, this strongly improved the visualization of strand networks and enabled quantitative morphometric analysis. Two populations of elliptic meshes (mean diameter <100 nm and 300-600 nm, respectively) were revealed. For Cld5 the two populations were more separated than for Cld3. Discrimination of non-polymeric molecules and molecules within polymeric strands was achieved. For both subtypes of claudins the mean density of detected molecules was similar and estimated to be ~24 times higher within the strands than outside the strands.The morphometry and single molecule information provided advances the mechanistic analysis of paracellular barriers. Applying this novel method to different TJ-proteins is expected to significantly improve the understanding of TJ on the molecular level. PMID- 22319609 TI - Can phlorotannins purified extracts constitute a novel pharmacological alternative for microbial infections with associated inflammatory conditions? AB - Bacterial and fungal infections and the emerging multidrug resistance are driving interest in fighting these microorganisms with natural products, which have generally been considered complementary to pharmacological therapies. Phlorotannins are polyphenols restricted to brown seaweeds, recognized for their biological capacity. This study represents the first research on the antibacterial, antifungal, anti-inflammatory and antioxidant activity of phlorotannins purified extracts, which were obtained from ten dominant brown seaweeds of the occidental Portuguese coast.Phlorotannins content was determined by the specific dimethoxybenzaldehyde (DMBA) method and a yield between 75 and 969 mg/Kg phloroglucinol units (dry matter) was obtained. Fucus spiralis ranked first, followed by three Cystoseira species. The anti-inflammatory potential of the purified extracts was assessed via inhibitory effect on nitric oxide (NO) production by lipopolysaccharide-stimulated RAW 264.7 macrophage cells, Cystoseira tamariscifolia being the one showing promising activity for the treatment of inflammation. NO scavenging ability was also addressed in cell free systems, F. spiralis being the species with highest capacity. The antimicrobial potential of the extracts was checked against five Gram-positive and four Gram negative bacteria and three fungi strains, that commonly colonize skin and mucosa and are responsible for food contamination. The different extracts were more effective against Gram-positive bacteria, Staphylococcus epidermidis being the most susceptible species. Concerning antifungal activity, Trichophyton rubrum was the most sensitive species.Although the molecular mechanisms underlying these properties remain poorly understood, the results obtained turn phlorotannins purified extracts a novel and potent pharmacological alternative for the treatment of a wide range of microbial infections, which usually also present an inflammatory component. In addition to the biological properties demonstrated herein, phlorotannins extracts may also be preferred, in order to avoid side effects and allergic reactions commonly associated with synthetic drugs. PMID- 22319610 TI - NEFL mRNA expression level is a prognostic factor for early-stage breast cancer patients. AB - Neurofilament, light polypeptide (NEFL) was demonstrated to be ectopically expressed in breast cancer tissues and decreased in lymph node metastases compared to the paired primary breast cancers in our previous study. Moreover, in several studies, NEFL was regarded as a tumor suppressor gene, and its loss of heterozygosity (LOH) was related to carcinogenesis and metastasis in several types of cancer. To explore the role of NEFL in the progression of breast cancer and to evaluate its clinical significance, we detected the NEFL mRNA level in normal breast tissues, primary breast cancer samples and lymph node metastases, and then analyzed the association between the NEFL expression level and several clinicopathological parameters and disease-free survival (DFS). NEFL mRNA was found to be expressed in 92.3% of breast malignancies and down-regulated in lymph node metastases compared to the paired primary tumors. NEFL mRNA level was lower in primary breast cancers with positive lymph nodes than in cancers with negative lymph nodes. Moreover, a low expression level of NEFL mRNA indicated a poor five year DFS for early-stage breast cancer patients. Thus, NEFL mRNA is ectopically expressed in breast malignancies and could be a potential prognostic factor for early-stage breast cancer patients. PMID- 22319611 TI - Protein solubility, digestibility and fractionation after germination of sorghum varieties. AB - The changes in crude protein, free amino acids, amino acid composition, protein solubility, protein fractionation and protein digestibility after germination of sorghum were investigated. Sorghum varieties (Dorado, Shandaweel-6, Giza-15) were soaked for 20 h followed by germination for 72 h; the results revealed that crude protein and free amino acids in raw sorghum varieties ranged from 10.62 to 12.46% and 0.66 to 1.03 mg/g, respectively. Shandaweel-6 was the highest variety in crude protein and free amino acids content. After germination, crude protein was decreased and free amino acids were increased. There was an increase in content of valine and phenylalanine amino acids after germination. On the other hand, there was a decrease in most of amino acids after germination. After germination protein solubility was significantly increased. Regarding protein fractions, there was an increase in albumin, globulin and kafirin proteins and a decrease in cross linked kafirin and cross linked glutelin after germination. PMID- 22319612 TI - Serum from calorie-restricted rats activates vascular cell eNOS through enhanced insulin signaling mediated by adiponectin. AB - eNOS activation resulting in mitochondrial biogenesis is believed to play a central role in life span extension promoted by calorie restriction (CR). We investigated the mechanism of this activation by treating vascular cells with serum from CR rats and found increased Akt and eNOS phosphorylation, in addition to enhanced nitrite release. Inhibiting Akt phosphorylation or immunoprecipitating adiponectin (found in high quantities in CR serum) completely prevented the increment in nitrite release and eNOS activation. Overall, we demonstrate that adiponectin in the serum from CR animals increases NO* signaling by activating the insulin pathway. These results suggest this hormone may be a determinant regulator of the beneficial effects of CR. PMID- 22319613 TI - Heterokaryon incompatibility is suppressed following conidial anastomosis tube fusion in a fungal plant pathogen. AB - It has been hypothesized that horizontal gene/chromosome transfer and parasexual recombination following hyphal fusion between different strains may contribute to the emergence of wide genetic variability in plant pathogenic and other fungi. However, the significance of vegetative (heterokaryon) incompatibility responses, which commonly result in cell death, in preventing these processes is not known. In this study, we have assessed this issue following different types of hyphal fusion during colony initiation and in the mature colony. We used vegetatively compatible and incompatible strains of the common bean pathogen Colletotrichum lindemuthianum in which nuclei were labelled with either a green or red fluorescent protein in order to microscopically monitor the fates of nuclei and heterokaryotic cells following hyphal fusion. As opposed to fusion of hyphae in mature colonies that resulted in cell death within 3 h, fusions by conidial anastomosis tubes (CAT) between two incompatible strains during colony initiation did not induce the vegetative incompatibility response. Instead, fused conidia and germlings survived and formed heterokaryotic colonies that in turn produced uninucleate conidia that germinated to form colonies with phenotypic features different to those of either parental strain. Our results demonstrate that the vegetative incompatibility response is suppressed during colony initiation in C. lindemuthianum. Thus, CAT fusion may allow asexual fungi to increase their genetic diversity, and to acquire new pathogenic traits. PMID- 22319614 TI - Role of the HaHOG1 MAP kinase in response of the conifer root and butt rot pathogen (heterobasidion annosum) to osmotic and oxidative stress [corrected]. AB - The basidiomycete Heterobasidion annosum (Fr.) Bref. s.l. is a filamentous white rot fungus, considered to be the most economically important pathogen of conifer trees. Despite the severity of the tree infection, very little is known about the molecular and biochemical aspects related to adaptation to abiotic stresses. In this study, the osmotic and oxidative tolerance as well as the role of the HaHOG1 Mitogen Activated Protein Kinase (MAPK) gene were investigated. The transcript levels of the yeast orthologues GPD1, HSP78, STL1, GRE2 and the ATPase pumps ENA1, PMR1, PMC1 known to have an important role in osmotolerance were also quantified under salt osmotic conditions. The HaHOG1 gene was used for a heterologous expression and functional study in the Saccharomyces cerevisiae Deltahog1 strain. Moreover, the phosphorylation level of HaHog1p was studied under salt osmotic and oxidative stress. The result showed that H. annosum displayed a decreased growth when exposed to an increased concentration of osmotic and oxidative stressors. GPD1, HSP78, STL1 and GRE2 showed an induction already at 10 min after exposure to salt stress. Among the ATPase pumps studied, PMC1 was highly induced when the fungus was exposed to 0.2 M CaCl2 for 60 min. The heterologous expression of the HaHOG1 sequence in yeast confirmed that the gene is able to restore the osmotolerance and oxidative tolerance in the S. cerevisiae hog1Delta mutant strain. The HaHog1p was strongly phosphorylated in the presence of NaCl, KCl, H2O2 but not in the presence of CaCl2 and MgCl2. The GFP-HaHog1p fusion protein accumulated in the nuclei of the S. cerevisiae hog1Delta cells when exposed to high osmotic conditions but not under oxidative stress. These results provide the first insights about the response of H. annosum to osmotic and oxidative stress and elucidate the role of the HaHOG1 gene in such conditions. PMID- 22319615 TI - In situ oxygen dynamics in coral-algal interactions. AB - BACKGROUND: Coral reefs degrade globally at an alarming rate, with benthic algae often replacing corals. However, the extent to which benthic algae contribute to coral mortality, and the potential mechanisms involved, remain disputed. Recent laboratory studies suggested that algae kill corals by inducing hypoxia on the coral surface, through stimulated microbial respiration. METHODS/FINDINGS: We examined the main premise of this hypothesis by measuring in situ oxygen microenvironments at the contact interface between the massive coral Porites spp. and turf algae, and between Porites spp. and crustose coralline algae (CCA). Oxygen levels at the interface were similar to healthy coral tissue and ranged between 300-400 uM during the day. At night, the interface was hypoxic (~70 uM) in coral-turf interactions and close to anoxic (~2 uM) in coral-CCA interactions, but these values were not significantly different from healthy tissue. The diffusive boundary layer (DBL) was about three times thicker at the interface than above healthy tissue, due to a depression in the local topography. A numerical model, developed to analyze the oxygen profiles above the irregular interface, revealed strongly reduced net photosynthesis and dark respiration rates at the coral-algal interface compared to unaffected tissue during the day and at night, respectively. CONCLUSIONS/SIGNIFICANCE: Our results showed that hypoxia was not a consistent feature in the microenvironment of the coral-algal interface under in situ conditions. Therefore, hypoxia alone is unlikely to be the cause of coral mortality. Due to the modified topography, the interaction zone is distinguished by a thicker diffusive boundary layer, which limits the local metabolic activity and likely promotes accumulation of potentially harmful metabolic products (e.g., allelochemicals and protons). Our study highlights the importance of mass transfer phenomena and the need for direct in situ measurements of microenvironmental conditions in studies on coral stress. PMID- 22319616 TI - Comparing pandemic to seasonal influenza mortality: moderate impact overall but high mortality in young children. AB - BACKGROUND: We assessed the severity of the 2009 influenza pandemic by comparing pandemic mortality to seasonal influenza mortality. However, reported pandemic deaths were laboratory-confirmed - and thus an underestimation - whereas seasonal influenza mortality is often more inclusively estimated. For a valid comparison, our study used the same statistical methodology and data types to estimate pandemic and seasonal influenza mortality. METHODS AND FINDINGS: We used data on all-cause mortality (1999-2010, 100% coverage, 16.5 million Dutch population) and influenza-like-illness (ILI) incidence (0.8% coverage). Data was aggregated by week and age category. Using generalized estimating equation regression models, we attributed mortality to influenza by associating mortality with ILI-incidence, while adjusting for annual shifts in association. We also adjusted for respiratory syncytial virus, hot/cold weather, other seasonal factors and autocorrelation. For the 2009 pandemic season, we estimated 612 (range 266-958) influenza-attributed deaths; for seasonal influenza 1,956 (range 0-3,990). 15,845 years-of-life-lost were estimated for the pandemic; for an average seasonal epidemic 17,908. For 0-4 yrs of age the number of influenza-attributed deaths during the pandemic were higher than in any seasonal epidemic; 77 deaths (range 61-93) compared to 16 deaths (range 0-45). The >=75 yrs of age showed a far below average number of deaths. Using pneumonia/influenza and respiratory/cardiovascular instead of all-cause deaths consistently resulted in relatively low total pandemic mortality, combined with high impact in the youngest age category. CONCLUSION: The pandemic had an overall moderate impact on mortality compared to 10 preceding seasonal epidemics, with higher mortality in young children and low mortality in the elderly. This resulted in a total number of pandemic deaths far below the average for seasonal influenza, and a total number of years-of-life-lost somewhat below average. Comparing pandemic and seasonal influenza mortality as in our study will help assessing the worldwide impact of the 2009 pandemic. PMID- 22319617 TI - Hydroxyl radical modification of collagen type II increases its arthritogenicity and immunogenicity. AB - BACKGROUND: The oxidation of proteins by endogenously generated free radicals causes structural modifications in the molecules that lead to generation of neo antigenic epitopes that have implications in various autoimmune disorders, including rheumatoid arthritis (RA). Collagen induced arthritis (CIA) in rodents (rats and mice) is an accepted experimental model for RA. METHODOLOGY/PRINCIPAL FINDINGS: Hydroxyl radicals were generated by the Fenton reaction. Collagen type II (CII) was modified by *OH radical (CII-OH) and analysed by ultraviolet-visible (UV-VIS), fluorescence and circular dichroism (CD) spectroscopy. The immunogenicity of native and modified CII was checked in female Lewis rats and specificity of the induced antibodies was ascertained by enzyme linked immunosorbent assay (ELISA). The extent of CIA was evaluated by visual inspection. We also estimated the oxidative and inflammatory markers in the sera of immunized rats. A slight change in the triple helical structure of CII as well as fragmentation was observed after hydroxyl radical modification. The modified CII was found to be highly arthritogenic and immunogenic as compared to the native form. The CII-OH immunized rats exhibited increased oxidative stress and inflammation as compared to the CII immunized rats in the control group. CONCLUSIONS/SIGNIFICANCE: Neo-antigenic epitopes were generated on (*)OH modified CII which rendered it highly immunogenic and arthritogenic as compared to the unmodified form. Since the rodent CIA model shares many features with human RA, these results illuminate the role of free radicals in human RA. PMID- 22319618 TI - MG63 osteoblast-like cells exhibit different behavior when grown on electrospun collagen matrix versus electrospun gelatin matrix. AB - Electrospinning is a simple and efficient method of fabricating a non-woven polymeric nanofiber matrix. However, using fluorinated alcohols as a solvent for the electrospinning of proteins often results in protein denaturation. TEM and circular dichroism analysis indicated a massive loss of triple-helical collagen from an electrospun collagen (EC) matrix, and the random coils were similar to those found in gelatin. Nevertheless, from mechanical testing we found the Young's modulus and ultimate tensile stresses of EC matrices were significantly higher than electrospun gelatin (EG) matrices because matrix stiffness can affect many cell behaviors such as cell adhesion, proliferation and differentiation. We hypothesize that the difference of matrix stiffness between EC and EG will affect intracellular signaling through the mechano-transducers Rho kinase (ROCK) and focal adhesion kinase (FAK) and subsequently regulates the osteogenic phenotype of MG63 osteoblast-like cells. From the results, we found there was no significant difference between the EC and EG matrices with respect to either cell attachment or proliferation rate. However, the gene expression levels of OPN, type I collagen, ALP, and OCN were significantly higher in MG63 osteoblast-like cells grown on the EC than in those grown on the EG. In addition, the phosphorylation levels of Y397-FAK, ERK1/2, BSP, and OPN proteins, as well as ALP activity, were also higher on the EC than on the EG. We further inhibited ROCK activation with Y27632 during differentiation to investigate its effects on matrix-mediated osteogenic differentiation. Results showed the extent of mineralization was decreased with inhibition after induction. Moreover, there is no significant difference between EC and EG. From the results of the protein levels of phosphorylated Y397-FAK, ERK1/2, BSP and OPN, ALP activity and mineral deposition, we speculate that the mechanism that influences the osteogenic differentiation of MG63 osteoblast-like cells on EC and EG is matrix stiffness and via ROCK-FAK-ERK1/2. PMID- 22319619 TI - Persistence versus escape: Aspergillus terreus and Aspergillus fumigatus employ different strategies during interactions with macrophages. AB - Invasive bronchopulmonary aspergillosis (IBPA) is a life-threatening disease in immunocompromised patients. Although Aspergillus terreus is frequently found in the environment, A. fumigatus is by far the main cause of IBPA. However, once A. terreus establishes infection in the host, disease is as fatal as A. fumigatus infections. Thus, we hypothesized that the initial steps of disease establishment might be fundamentally different between these two species. Since alveolar macrophages represent one of the first phagocytes facing inhaled conidia, we compared the interaction of A. terreus and A. fumigatus conidia with alveolar macrophages. A. terreus conidia were phagocytosed more rapidly than A. fumigatus conidia, possibly due to higher exposure of beta-1,3-glucan and galactomannan on the surface. In agreement, blocking of dectin-1 and mannose receptors significantly reduced phagocytosis of A. terreus, but had only a moderate effect on phagocytosis of A. fumigatus. Once phagocytosed, and in contrast to A. fumigatus, A. terreus did not inhibit acidification of phagolysosomes, but remained viable without signs of germination both in vitro and in immunocompetent mice. The inability of A. terreus to germinate and pierce macrophages resulted in significantly lower cytotoxicity compared to A. fumigatus. Blocking phagolysosome acidification by the v-ATPase inhibitor bafilomycin increased A. terreus germination rates and cytotoxicity. Recombinant expression of the A. nidulans wA naphthopyrone synthase, a homologue of A. fumigatus PksP, inhibited phagolysosome acidification and resulted in increased germination, macrophage damage and virulence in corticosteroid-treated mice. In summary, we show that A. terreus and A. fumigatus have evolved significantly different strategies to survive the attack of host immune cells. While A. fumigatus prevents phagocytosis and phagolysosome acidification and escapes from macrophages by germination, A. terreus is rapidly phagocytosed, but conidia show long-term persistence in macrophages even in immunocompetent hosts. PMID- 22319620 TI - Multiple intravenous administrations of human umbilical cord blood cells benefit in a mouse model of ALS. AB - BACKGROUND: A promising therapeutic strategy for amyotrophic lateral sclerosis (ALS) is the use of cell-based therapies that can protect motor neurons and thereby retard disease progression. We recently showed that a single large dose (25 * 106 cells) of mononuclear cells from human umbilical cord blood (MNC hUCB) administered intravenously to pre-symptomatic G93A SOD1 mice is optimal in delaying disease progression and increasing lifespan. However, this single high cell dose is impractical for clinical use. The aim of the present pre-clinical translation study was therefore to evaluate the effects of multiple low dose systemic injections of MNC hUCB cell into G93A SOD1 mice at different disease stages. METHODOLOGY/PRINCIPAL FINDINGS: Mice received weekly intravenous injections of MNC hUCB or media. Symptomatic mice received 106 or 2.5 * 106 cells from 13 weeks of age. A third, pre-symptomatic, group received 106 cells from 9 weeks of age. Control groups were media-injected G93A and mice carrying the normal hSOD1 gene. Motor function tests and various assays determined cell effects. Administered cell distribution, motor neuron counts, and glial cell densities were analyzed in mouse spinal cords. Results showed that mice receiving 106 cells pre-symptomatically or 2.5 * 106 cells symptomatically significantly delayed functional deterioration, increased lifespan and had higher motor neuron counts than media mice. Astrocytes and microglia were significantly reduced in all cell-treated groups. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that multiple injections of MNC hUCB cells, even beginning at the symptomatic disease stage, could benefit disease outcomes by protecting motor neurons from inflammatory effectors. This multiple cell infusion approach may promote future clinical studies. PMID- 22319621 TI - In silico insights into the symbiotic nitrogen fixation in Sinorhizobium meliloti via metabolic reconstruction. AB - BACKGROUND: Sinorhizobium meliloti is a soil bacterium, known for its capability to establish symbiotic nitrogen fixation (SNF) with leguminous plants such as alfalfa. S. meliloti 1021 is the most extensively studied strain to understand the mechanism of SNF and further to study the legume-microbe interaction. In order to provide insight into the metabolic characteristics underlying the SNF mechanism of S. meliloti 1021, there is an increasing demand to reconstruct a metabolic network for the stage of SNF in S. meliloti 1021. RESULTS: Through an iterative reconstruction process, a metabolic network during the stage of SNF in S. meliloti 1021 was presented, named as iHZ565, which accounts for 565 genes, 503 internal reactions, and 522 metabolites. Subjected to a novelly defined objective function, the in silico predicted flux distribution was highly consistent with the in vivo evidences reported previously, which proves the robustness of the model. Based on the model, refinement of genome annotation of S. meliloti 1021 was performed and 15 genes were re-annotated properly. There were 19.8% (112) of the 565 metabolic genes included in iHZ565 predicted to be essential for efficient SNF in bacteroids under the in silico microaerobic and nutrient sharing condition. CONCLUSIONS: As the first metabolic network during the stage of SNF in S. meliloti 1021, the manually curated model iHZ565 provides an overview of the major metabolic properties of the SNF bioprocess in S. meliloti 1021. The predicted SNF-required essential genes will facilitate understanding of the key functions in SNF and help identify key genes and design experiments for further validation. The model iHZ565 can be used as a knowledge based framework for better understanding the symbiotic relationship between rhizobia and legumes, ultimately, uncovering the mechanism of nitrogen fixation in bacteroids and providing new strategies to efficiently improve biological nitrogen fixation. PMID- 22319622 TI - Iterative evolution of sympatric seacow (Dugongidae, Sirenia) assemblages during the past ~26 million years. AB - Extant sirenians show allopatric distributions throughout most of their range. However, their fossil record shows evidence of multispecies communities throughout most of the past ~26 million years, in different oceanic basins. Morphological differences among co-occurring sirenian taxa suggest that resource partitioning played a role in structuring these communities. We examined body size and ecomorphological differences (e.g., rostral deflection and tusk morphology) among sirenian assemblages from the late Oligocene of Florida, early Miocene of India and early Pliocene of Mexico; each with three species of the family Dugongidae. Although overlapping in several ecomorphological traits, each assemblage showed at least one dominant trait in which coexisting species differed. Fossil sirenian occurrences occasionally are monotypic, but the assemblages analyzed herein show iterative evolution of multispecies communities, a phenomenon unparalleled in extant sirenian ecology. As primary consumers of seagrasses, these communities likely had a strong impact on past seagrass ecology and diversity, although the sparse fossil record of seagrasses limits direct comparisons. Nonetheless, our results provide robust support for previous suggestions that some sirenians in these extinct assemblages served as keystone species, controlling the dominance of climax seagrass species, permitting more taxonomically diverse seagrass beds (and sirenian communities) than many of those observed today. PMID- 22319623 TI - Standardized terminology and potential taxonomic utility for hadrosaurid skin impressions: a case study for Saurolophus from Canada and Mongolia. AB - The characterization of palaeospecies typically relies on hard-tissue anatomy, such as bones or teeth that is more readily fossilized than soft parts. Among dinosaurs, skin impressions are commonly associated with partial and complete hadrosaurid skeletons, and consist of non-imbricating tubercles or scales. Skin impressions from various parts of the body of two species of the hadrosaurine Saurolophus (S. angustirostris from Mongolia and S. osborni from Canada) are described from multiple specimens. These species, recently validated on osteological grounds, can be differentiated based solely on soft-tissue anatomy, namely scale shape and pattern. This study demonstrates for the first time the applicability of soft-tissue (i.e., scale impressions) as a means to differentiate species within the Dinosauria. Differences are most spectacular in the tail, where S. angustirostris is differentiated by the presence of vertical bands of morphologically distinct scales, a grid-like arrangement of circular feature-scales, and tabular scales along the dorsal midline. Preliminary results indicate scale architecture remained consistent throughout ontogeny in S. angustirostris. These results support previous assertions that hadrosaurid scale architecture has a positive phylogenetic signal. As such, future taxonomic descriptions should include, where possible, the standardized description of skin impressions including the position and orientation of these impressions on the body. PMID- 22319624 TI - Preventive effects of omega-3 and omega-6 Fatty acids on peroxide mediated oxidative stress responses in primary human trabecular meshwork cells. AB - Pathologic processes in glaucoma include increased apoptosis, accumulation of extracellular material in the trabecular meshwork and optic nerve, condensations of the cytoskeleton and precocious cellular senescence. Oxidative stress was shown to generate these alterations in primary ocular cells. Fatty acids omega-3 and -6 are alleged to constitute a prophylaxis against these deleterious effects. Here, we tested actual preventive effects omega-3 and -6 against peroxide induced stress responses in primary human trabecular meshwork cells. Changes of mitochondrial activity, proliferation, heat shock proteins, extracellular matrix components, and inflammatory markers were evaluated. Alterations of the cytoskeleton were evaluated by phalloidin labeling. Here we report a repressive effect of omega-6 on metabolic activity and proliferation, which was not detected for omega-3. Both agents were able to prevent the anti-proliferative effect of H2O2, but only omega-3 prevented metabolic repression. Expression of heat shock protein 27 was unaltered by both fatty acids, whereas heat shock protein 90 was significantly induced by both. Omega-6 increased fibronectin and connective tissue growth factor synthesis, as well as the amount of secreted fibronectin. Omega-3, instead, induced plasminogen activator inhibitor 1 synthesis. H2O2 further increased fibronectin production in omega-6 supplemented cells, which was not the case in omega-3 treated cells. H2O2 stimulation of plasminogen activator inhibitor 1 and connective tissue growth factor was repressed by both fatty acids. Both fatty acids appeared to abolish H2O2 mediated stimulation of nuclear factor kappaB and IL-6, but not IL-1alpha and IL-8. H2O2 induced formation of cross-linked actin networks and stress fibers, which was reduced by preemptive application of omega-3. Omega-6, in contrast, had no protective effect on that, and even seemed to promote condensation. Based on the observed side effects of omega-6, omega-3 appears to be the more beneficial fatty acid in respect of prophylactic intake for prevention of a glaucomatous disease. PMID- 22319625 TI - Characterization of three novel SINE families with unusual features in Helicoverpa armigera. AB - Although more than 120 families of short interspersed nuclear elements (SINEs) have been isolated from the eukaryotic genomes, little is known about SINEs in insects. Here, we characterize three novel SINEs from the cotton bollworm, Helicoverpa armigera. Two of them, HaSE1 and HaSE2, share similar 5' -structure including a tRNA-related region immediately followed by conserved central domain. The 3' -tail of HaSE1 is significantly similar to that of one LINE retrotransposon element, HaRTE1.1, in H. armigera genome. The 3' -region of HaSE2 showed high identity with one mariner-like element in H. armigera. The third family, termed HaSE3, is a 5S rRNA-derived SINE and shares both body part and 3' tail with HaSE1, thus may represent the first example of a chimera generated by recombination between 5S rRNA and tRNA-derived SINE in insect species. Further database searches revealed the presence of these SINEs in several other related insect species, but not in the silkworm, Bombyx mori, indicating a relatively narrow distribution of these SINEs in Lepidopterans. Apart from above, we found a copy of HaSE2 in the GenBank EST entry for the cotton aphid, Aphis gossypii, suggesting the occurrence of horizontal transfer. PMID- 22319626 TI - Klotho lacks a vitamin D independent physiological role in glucose homeostasis, bone turnover, and steady-state PTH secretion in vivo. AB - Apart from its function as co-receptor for fibroblast growth factor-23 (FGF23), Klotho is thought to regulate insulin signaling, intracellular oxidative stress, and parathyroid hormone (PTH) secretion in an FGF23 independent fashion. Here, we crossed Klotho deficient (Kl-/-) mice with vitamin D receptor (VDR) mutant mice to examine further vitamin D independent functions of Klotho. All mice were fed a rescue diet enriched with calcium, phosphorus, and lactose to prevent hyperparathyroidism in VDR mutants, and were killed at 4 weeks of age after double fluorochrome labeling. Kl-/- mice displayed hypercalcemia, hyperphosphatemia, dwarfism, organ atrophy, azotemia, pulmonary emphysema, and osteomalacia. In addition, glucose and insulin tolerance tests revealed hypoglycemia and profoundly increased peripheral insulin sensitivity in Kl-/- mice. Compound mutants were normocalcemic and normophosphatemic, did not show premature aging or organ atrophy, and were phenocopies of VDR mutant mice in terms of body weight, bone mineral density, bone metabolism, serum calcium, serum phosphate, serum PTH, gene expression in parathyroid glands, as well as urinary calcium and phosphate excretion. Furthermore, ablation of vitamin D signaling in double mutants completely normalized glucose and insulin tolerance, indicating that Klotho has no vitamin D independent effects on insulin signaling. Histomorphometry of pancreas islets showed similar beta cell volume per body weight in all groups of animals. In conclusion, our findings cast doubt on a physiologically relevant vitamin D and Fgf23 independent function of Klotho in the regulation of glucose metabolism, bone turnover, and steady-state PTH secretion in vivo. PMID- 22319627 TI - Homocysteinylated albumin promotes increased monocyte-endothelial cell adhesion and up-regulation of MCP1, Hsp60 and ADAM17. AB - RATIONALE: The cardiovascular risk factor homocysteine is mainly bound to proteins in human plasma, and it has been hypothesized that homocysteinylated proteins are important mediators of the toxic effects of hyperhomocysteinemia. It has been recently demonstrated that homocysteinylated proteins are elevated in hemodialysis patients, a high cardiovascular risk population, and that homocysteinylated albumin shows altered properties. OBJECTIVE: Aim of this work was to investigate the effects of homocysteinylated albumin - the circulating form of this amino acid, utilized at the concentration present in uremia - on monocyte adhesion to a human endothelial cell culture monolayer and the relevant molecular changes induced at both cell levels. METHODS AND RESULTS: Treated endothelial cells showed a significant increase in monocyte adhesion. Endothelial cells showed after treatment a significant, specific and time-dependent increase in ICAM1 and VCAM1. Expression profiling and real time PCR, as well as protein analysis, showed an increase in the expression of genes encoding for chemokines/cytokines regulating the adhesion process and mediators of vascular remodeling (ADAM17, MCP1, and Hsp60). The mature form of ADAM17 was also increased as well as Tnf-alpha released in the cell medium. At monocyte level, treatment induced up-regulation of ICAM1, MCP1 and its receptor CCR2. CONCLUSIONS: Treatment with homocysteinylated albumin specifically increases monocyte adhesion to endothelial cells through up-regulation of effectors involved in vascular remodeling. PMID- 22319628 TI - Determinants of natural mating success in the cannibalistic orb-web spider Argiope bruennichi. AB - Monogynous mating systems (low male mating rates) occur in various taxa and have evolved several times independently in spiders. Monogyny is associated with remarkable male mating strategies and predicted to evolve under a male-biased sex ratio. While male reproductive strategies are well documented and male mating rates are easy to quantify, especially in sexually cannibalistic species, female reproductive strategies, the optimal female mating rate, and the factors that affect the evolution of female mating rates are still unclear. In this study, we examined natural female mating rates and tested the assumption of a male-biased sex ratio and female polyandry in a natural population of Argiope bruennichi in which we controlled female mating status prior to observations. We predicted variation in female mating frequencies as a result of spatial and temporal heterogeneity in the distribution of mature females and males. Females had a low average mating rate of 1.3 and the majority copulated only once. Polyandry did not entirely result from a male-biased sex-ratio but closely matched the rate of male bigamy. Male activity and the probability of polyandry correlated with factors affecting pheromone presence such as virgin females' density. We conclude that a strong sex ratio bias and high female mating rates are not necessary components of monogynous mating systems as long as males protect their paternity effectively and certain frequencies of bigyny stabilise the mating system. PMID- 22319629 TI - Reduced risk of malaria parasitemia following household screening and treatment: a cross-sectional and longitudinal cohort study. AB - BACKGROUND: In regions of declining malaria transmission, new strategies for control are needed to reduce transmission and achieve elimination. Artemisinin combination therapy (ACT) is active against immature gametocytes and can reduce the risk of transmission. We sought to determine whether household screening and treatment of infected individuals provides protection against infection for household members. METHODOLOGY/PRINCIPAL FINDINGS: The study was conducted in two areas in Southern Province, Zambia in 2007 and 2008/2009. To determine the impact of proactive case detection, households were randomly selected either to join a longitudinal cohort, in which participants were repeatedly screened throughout the year and those infected treated with artemether-lumefantrine, or a cross sectional survey, in which participants were visited only once. Cross-sectional surveys were conducted throughout the year. The prevalence of RDT positivity was compared between the longitudinal and cross-sectional households at baseline and during follow-up using multilevel logistic regression. In the 2007 study area, 174 and 156 participants enrolled in the cross-sectional and longitudinal groups, respectively. In the 2008/2009 study area, 917 and 234 participants enrolled in the cross-sectional and longitudinal groups, respectively. In both study areas, participants and households in the longitudinal and cross-sectional groups were similar on demographic characteristics and prevalence of RDT positivity at baseline (2007: OR = 0.97; 95% CI:0.46, 2.03 | 2008/2009: OR = 1.28; 95% CI:0.44, 3.79). After baseline, the prevalence of RDT positivity was significantly lower in longitudinal compared to cross-sectional households in both study areas (2007: OR = 0.44; 95% CI:0.20, 0.96 | 2008/2009: OR = 0.16; 95% CI:0.05, 0.55). CONCLUSIONS/SIGNIFICANCE: Proactive case detection, consisting of screening household members with an RDT and treating those positive with ACT, can reduce transmission and provide indirect protection to household members. A targeted test and treat strategy could contribute to the elimination of malaria in regions of low transmission. PMID- 22319630 TI - Melanoma cell expression of CD200 inhibits tumor formation and lung metastasis via inhibition of myeloid cell functions. AB - CD200 is a cell surface glycoprotein that functions through engaging CD200 receptor on cells of the myeloid lineage and inhibits their functions. Expression of CD200 has been implicated in a variety of human cancer cells including melanoma cells and has been thought to play a protumor role. To investigate the role of cancer cell expression of CD200 in tumor formation and metastasis, we generated CD200-positive and CD200-negative B16 melanoma cells. Subcutaneous injection of CD200-positive B16 melanoma cells inhibited tumor formation and growth in C57BL/6 mice but not in Rag1-/-C57BL/6 mice. However, i.v. injection of CD200-positive B16 melanoma cells dramatically inhibited tumor foci formation in the lungs of both C57BL/6 and Rag1-/-C57BL6 mice. Flow cytometry analysis revealed higher expression of CD200R in Gr1+ myeloid cells in the lung than in peripheral myeloid cells. Depletion of Gr1+ cells or stimulation of CD200R with an agonistic antibody in vivo dramatically inhibited tumor foci formation in the lungs. In addition, treatment with tumor antigen specific CD4 or CD8 T cells or their combination yielded a survival advantage for CD200 positive tumor bearing mice over mice bearing CD200-negative tumors. Taken together, we have revealed a novel role for CD200-CD200R interaction in inhibiting tumor formation and metastasis. Targeting CD200R may represent a novel approach for cancer immunotherapy. PMID- 22319631 TI - Variation in Hsp70 levels after cold shock: signs of evolutionary responses to thermal selection among Leptinotarsa decemlineata populations. AB - Individuals of widely spread species are expected to show local adaption in temperature tolerance as they encounter a range of thermal conditions. We tracked thermal adaptations of the Colorado potato beetle (Leptinotarsa decemlineata) that invaded Europe within the last 100 years. It has occupied various conditions although, like the majority of invasive species, it lost a measurable amount of neutral genetic variation due to bottleneck effect when it invaded Europe. We exposed diapausing beetles originated from three different latitudes (54 degrees N, 59 degrees N, 60 degrees N) to cold shock (-5 degrees C, 1.5 hrs) in order to test if beetles from the northern populations express differential levels of cold induced and constitutive Hsp70 compared to the beetles from milder temperature regime. The level of cold-induced Hsp70 was lowest in the northernmost beetle populations while the level of constitutive Hsp70 did not differ with the population. Moreover, the southernmost beetles were more plastic in their response to cold shock than the northernmost beetles. These results suggest that physiological adaptation, like the synthesis of Hsp70, can evolve very quickly. PMID- 22319632 TI - MicroRNA-520b inhibits growth of hepatoma cells by targeting MEKK2 and cyclin D1. AB - Growing evidence indicates that the deregulation of microRNAs (miRNAs) contributes to the tumorigenesis. We previously revealed that microRNA-520b (miR 520b) was involved in the complement attack and migration of breast cancer cells. In this report, we show that miR-520b is an important miRNA in the development of hepatocellular carcinoma (HCC). Our data showed that the expression levels of miR 520b were significantly reduced in clinical HCC tissues and hepatoma cell lines. We observed that the introduction of miR-520b dramatically suppressed the growth of hepatoma cells by colony formation assays, 5-ethynyl-2-deoxyuridine (EdU) incorporation assays and 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Moreover, ectopic expression of miR-520b was able to inhibit the growth of hepatoma cells in nude mice. Further studies revealed that the mitogen-activated protein kinase kinase kinase 2 (MEKK2) and cyclin D1 were two of direct target genes of miR-520b. Silencing of MEKK2 or cyclin D1 was able to inhibit the growth of hepatoma cells in vitro and in vivo, which is consistent with the effect of miR-520b overexpression on the growth of hepatoma cells. In addition, miR-520b significantly decreased the phosphorylation levels of c-Jun N terminal kinase (p-JNK, a downstream effector of MEKK2) or retinoblastoma (p-Rb, a downstream effector of cyclin D1). In conclusion, miR-520b is able to inhibit the growth of hepatoma cells by targeting MEKK2 or cyclin D1 in vitro and in vivo. Our findings provide new insights into the role of miR-520b in the development of HCC, and implicate the potential application of miR-520b in cancer therapy. PMID- 22319633 TI - Pentraxin-3 as a marker of advanced atherosclerosis results from the Bruneck, ARMY and ARFY Studies. AB - OBJECTIVE: Pentraxins like C-reactive protein are key components of the innate immune system. Recently, pentraxin-3 (PTX3) has been proposed to be a specific marker of vascular inflammation, yet its association with atherosclerosis is still unclear. METHODS AND RESULTS: PTX3 serum levels were measured in three independent studies of 132 young men (ARMY Study), 205 young women (ARFY Study) and 562 individuals 55 to 94 years old (Bruneck Study). In contrast to C-reactive protein, PTX3 showed little relationships with classic vascular risk factors and pro-inflammatory conditions. In the population based Bruneck Study, PTX3 level was independently associated with prevalent cardiovascular diseases (multivariable odds ratio [95%CI] 3.09 [1.65-5.79]; P<0.001). Moreover, PTX3 level correlated with the severity of carotid and femoral atherosclerosis and was highest in individuals with multiple vascular territories affected. In contrast, there was no association with elevated intima-media thickness, a precursor lesion of atherosclerosis, in any of the three populations investigated. CONCLUSIONS: Level of PTX3 is independently associated with atherosclerosis and manifest cardiovascular disease but not early vessel pathology. Unlike C-reactive protein, PTX3 is not a component of the classic acute phase response (systemic inflammation) but appears to be more specific for vascular inflammation. PMID- 22319634 TI - Seascape genetics of a globally distributed, highly mobile marine mammal: the short-beaked common dolphin (genus Delphinus). AB - Identifying which factors shape the distribution of intraspecific genetic diversity is central in evolutionary and conservation biology. In the marine realm, the absence of obvious barriers to dispersal can make this task more difficult. Nevertheless, recent studies have provided valuable insights into which factors may be shaping genetic structure in the world's oceans. These studies were, however, generally conducted on marine organisms with larval dispersal. Here, using a seascape genetics approach, we show that marine productivity and sea surface temperature are correlated with genetic structure in a highly mobile, widely distributed marine mammal species, the short-beaked common dolphin. Isolation by distance also appears to influence population divergence over larger geographical scales (i.e. across different ocean basins). We suggest that the relationship between environmental variables and population structure may be caused by prey behaviour, which is believed to determine common dolphins' movement patterns and preferred associations with certain oceanographic conditions. Our study highlights the role of oceanography in shaping genetic structure of a highly mobile and widely distributed top marine predator. Thus, seascape genetic studies can potentially track the biological effects of ongoing climate-change at oceanographic interfaces and also inform marine reserve design in relation to the distribution and genetic connectivity of charismatic and ecologically important megafauna. PMID- 22319635 TI - Multiple distant origins for green sea turtles aggregating off Gorgona Island in the Colombian eastern Pacific. AB - Mitochondrial DNA analyses have been useful for resolving maternal lineages and migratory behavior to foraging grounds (FG) in sea turtles. However, little is known about source rookeries and haplotype composition of foraging green turtle aggregations in the southeastern Pacific. We used mitochondrial DNA control region sequences to identify the haplotype composition of 55 green turtles, Chelonia mydas, captured in foraging grounds of Gorgona National Park in the Colombian Pacific. Amplified fragments of the control region (457 bp) revealed the presence of seven haplotypes, with haplotype (h) and nucleotide (pi) diversities of h = 0.300+/-0.080 and pi = 0.009+/-0.005 respectively. The most common haplotype was CMP4 observed in 83% of individuals, followed by CMP22 (5%). The genetic composition of the Gorgona foraging population primarily comprised haplotypes that have been found at eastern Pacific rookeries including Mexico and the Galapagos, as well as haplotypes of unknown stock origin that likely originated from more distant western Pacific rookeries. Mixed stock analysis suggests that the Gorgona FG population is comprised mostly of animals from the Galapagos rookery (80%). Lagrangian drifter data showed that movement of turtles along the eastern Pacific coast and eastward from distant western and central Pacific sites was possible through passive drift. Our results highlight the importance of this protected area for conservation management of green turtles recruited from distant sites along the eastern Pacific Ocean. PMID- 22319636 TI - InsR/FoxO1 signaling curtails hypothalamic POMC neuron number. AB - Insulin receptor (InsR) signaling through transcription factor FoxO1 is important in the development of hypothalamic neuron feeding circuits, but knowledge about underlying mechanisms is limited. To investigate the role of InsR/FoxO1 signaling in the development and maintenance of these circuits, we surveyed the pool of hypothalamic neurons expressing Pomc mRNA in different mouse models of impaired hypothalamic InsR signaling. InsR ablation in the entire hypothalamus did not affect Pomc-neuron number at birth, but resulted in a 25% increase, most notably in the middle arcuate nucleus region, in young adults. Selective restoration of InsR expression in POMC neurons in these mice partly reversed the abnormality, resulting in a 10% decrease compared to age-matched controls. To establish whether FoxO1 signaling plays a role in this process, we examined POMC neuron number in mice with POMC-specific deletion of FoxO1, and detected a 23% decrease in age-matched animals, consistent with a cell-autonomous role of InsR/FoxO1 signaling in regulating POMC neuron number, distinct from its established role to activate Pomc transcription. These changes in Pomc cells occurred in the absence of marked changes in humoral factors or hypothalamic NPY neurons. PMID- 22319637 TI - The gene expression analysis of blood reveals S100A11 and AQP9 as potential biomarkers of infective endocarditis. AB - BACKGROUND: The diagnostic and prognostic assessments of infective endocarditis (IE) are challenging. To investigate the host response during IE and to identify potential biomarkers, we determined the circulating gene expression profile using whole genome microarray analysis. METHODS AND RESULTS: A transcriptomic case control study was performed on blood samples from patients with native valve IE (n = 39), excluded IE after an initial suspicion (n = 10) at patient's admission, and age-matched healthy controls (n = 10). Whole genome microarray analysis showed that patients with IE exhibited a specific transcriptional program with a predominance of gene categories associated with cell activation as well as innate immune and inflammatory responses. Quantitative real-time RT-PCR performed on a selection of highly modulated genes showed that the expression of the gene encoding S100 calcium binding protein A11 (S100A11) was significantly increased in patients with IE in comparison with controls (P<0.001) and patients with excluded IE (P<0.05). Interestingly, the upregulated expression of the S100A11 gene was more pronounced in staphylococcal IE than in streptococcal IE (P<0.01). These results were confirmed by serum concentrations of the S100A11 protein. Finally, we showed that in patients with IE, the upregulation of the aquaporin-9 gene (AQP9) was significantly associated with the occurrence of acute heart failure (P = 0.02). CONCLUSIONS: Using transcriptional signatures of blood samples, we identified S100A11 as a potential diagnostic marker of IE, and AQP9 as a potential prognostic factor. PMID- 22319638 TI - Changes in cGMP levels affect the localization of EGL-4 in AWC in Caenorhabditis elegans. AB - The Protein Kinase G, EGL-4, is required within the C. elegans AWC sensory neurons to promote olfactory adaptation. After prolonged stimulation of these neurons, EGL-4 translocates from the cytosol to the nuclei of the AWC. This nuclear translocation event is both necessary and sufficient for adaptation of the AWC neuron to odor. A cGMP binding motif within EGL-4 and the Galpha protein ODR-3 are both required for this translocation event, while loss of the guanylyl cyclase ODR-1 was shown to result in constitutively nuclear localization of EGL 4. However, the molecular changes that are integrated over time to produce a stably adapted response in the AWC are unknown. Here we show that odor-induced fluctuations in cGMP levels in the adult cilia may be responsible in part for sending EGL-4 into the AWC nucleus to produce long-term adaptation. We found that reductions in cGMP that result from mutations in the genes encoding the cilia localized guanylyl cyclases ODR-1 and DAF-11 result in constitutively nuclear EGL 4 even in naive animals. Conversely, increases in cGMP levels that result from mutations in cGMP phosphodiesterases block EGL-4 nuclear entry even after prolonged odor exposure. Expression of a single phosphodiesterase in adult, naive animals was sufficient to modestly increase the number of animals with nuclear EGL-4. Further, coincident acute treatment of animals with odor and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) decreased the number of animals with nuclear EGL-4. These data suggest that reducing cGMP levels in AWC is necessary and even partially sufficient for nuclear translocation of EGL-4 and adaptation as a result of prolonged odor exposure. Our genetic analysis and chemical treatment of C. elegans further indicate that cilia morphology, as defined by fluorescent microscopic observation of the sensory endings, may allow for odor-induced fluctuations in cGMP levels and this fluctuation may be responsible for sending EGL-4 into the AWC nucleus. PMID- 22319639 TI - The role of circulating serotonin in the development of chronic obstructive pulmonary disease. AB - BACKGROUND: Cigarette smoking is a major risk factor in the development of age related chronic obstructive pulmonary disease (COPD). The serotonin transporter (SERT) gene polymorphism has been reported to be associated with COPD, and the degree of cigarette smoking has been shown to be a significant mediator in this relationship. The interrelation between circulating serotonin (5 hydroxytyptamine, 5-HT), cigarette smoking and COPD is however largely unknown. The current study aimed at investigating the mediation effects of plasma 5-HT on cigarette smoking-induced COPD and the relation between plasma 5-HT levels and age. METHODS: The association between plasma 5-HT, age and COPD was analyzed in a total of 62 COPD patients (ever-smokers) and 117 control subjects (healthy non smokers and ever-smokers). Plasma 5-HT levels were measured by enzyme-linked immuno assay (EIA). RESULTS: The elevated plasma 5-HT levels were significantly associated with increased odds for COPD (OR = 1.221, 95% CI = 1.123 to 1.319, p<0.0001). The effect remained significant after being adjusted for age and pack years smoked (OR = 1.271, 95% CI = 1.134 to 1.408, p = 0.0003). Furthermore, plasma 5-HT was found to mediate the relation between pack-years smoked and COPD. A positive correlation (r = 0.303, p = 0.017) was found between plasma 5-HT levels and age in COPD, but not in the control subjects (r = -0.149, p = 0.108). CONCLUSION: Our results suggest that cigarette smoke-induced COPD is partially mediated by the plasma levels of 5-HT, and that these become elevated with increased age in COPD. The elevated plasma 5-HT levels in COPD might contribute to the pathogenesis of this disease. PMID- 22319640 TI - Scientific standards and the regulation of genetically modified insects. PMID- 22319642 TI - Workshop attendees suggest methods to improve the number and advancement of women scientists in NanoScience/NanoTechnology. PMID- 22319641 TI - Comparative modeling of PON2 and analysis of its substrate binding interactions using computational methods. AB - Paraoxonase (PON) constitutes a family of calcium-dependent mammalian enzymes comprising of PON1, PON2, and PON3. PON family shares ~60% sequence homology. These enzymes exhibit multiple activities like paraoxonase, arylesterase, and lactonase in a substrate dependent manner. Decreased PON activity has been reported in diseases like cardiovascular disease, atherosclerosis, and diabetes. Even though, PON2 is the oldest member of the family, PON1 is the only member studied in silico. In this study, the structure of PON2 was modeled using MODELLER 9v7 and its interactions with relevant ligands and it's physiological substrate homocysteine thiolactone was performed using AutoDock 4.0. The results reveal that PON1 and PON2 share common ligand binding patterns for arylesterase and lactonase activity, whereas in case of paraoxon binding, the residues involved in the interactions were different. Interestingly, the substrate HCTL was found to have the lowest free energy of binding (DeltaG) and highest affinity for PON2 than PON1. PMID- 22319643 TI - New cardiovascular and pulmonary therapeutic strategies based on the Angiotensin converting enzyme 2/angiotensin-(1-7)/mas receptor axis. AB - Angiotensin (Ang)-(1-7) is now recognized as a biologically active component of the renin-angiotensin system (RAS). The discovery of the angiotensin-converting enzyme homologue ACE2 revealed important metabolic pathways involved in the Ang (1-7) synthesis. This enzyme can form Ang-(1-7) from Ang II or less efficiently through hydrolysis of Ang I to Ang-(1-9) with subsequent Ang-(1-7) formation. Additionally, it is well established that the G protein-coupled receptor Mas is a functional ligand site for Ang-(1-7). The axis formed by ACE2/Ang-(1-7)/Mas represents an endogenous counter regulatory pathway within the RAS whose actions are opposite to the vasoconstrictor/proliferative arm of the RAS constituted by ACE/Ang II/AT(1) receptor. In this review we will discuss recent findings concerning the biological role of the ACE2/Ang-(1-7)/Mas arm in the cardiovascular and pulmonary system. Also, we will highlight the initiatives to develop potential therapeutic strategies based on this axis. PMID- 22319644 TI - Phytoestrogens enhance the vascular actions of the endocannabinoid anandamide in mesenteric beds of female rats. AB - In rat isolated mesenteric beds that were contracted with NA as an in vitro model of the vascular adrenergic hyperactivity that usually precedes the onset of primary hypertension, the oral administration (3 daily doses) of either 10 mg/kg genistein or 20 mg/kg daidzein potentiated the anandamide-induced reduction of contractility to NA in female but not in male rats. Oral treatment with phytoestrogens also restored the vascular effects of anandamide as well as the mesenteric content of calcitonin gene-related peptide (CGRP) that were reduced after ovariectomy. The enhancement of anandamide effects caused by phytoestrogens was prevented by the concomitant administration of the estrogen receptor antagonist fulvestrant (2.5 mg/kg, s.c., 3 daily doses). It is concluded that, in the vasculature of female rats, phytoestrogens produced an estrogen-receptor dependent enhancement of the anandamide-vascular actions that involves the modulation of CGRP levels and appears to be relevant whenever an adrenergic hyperactivity occurs. PMID- 22319645 TI - Renoprotective Effects of AVE0991, a Nonpeptide Mas Receptor Agonist, in Experimental Acute Renal Injury. AB - Renal ischemia and reperfusion (I/R) is the major cause of acute kidney injury in hospitalized patients. Mechanisms underlying reperfusion-associated injury include recruitment and activation of leukocytes and release of inflammatory mediators. In this study, we investigated the renal effects of acute administration of AVE0991, an agonist of Mas, the angiotensin-(1-7) receptor, the angiotensin-(1-7) receptor, in a murine model of renal I/R. Male C57BL/6 wild type or Mas(-/-) mice were subjected to 30 min of bilateral ischemia and 24 h of reperfusion. Administration of AVE0991 promoted renoprotective effects, as seen by improvement of function, decreased tissue injury, prevention of local and remote leucocyte infiltration, and release of the chemokine, CXCL1. I/R injury was similar in WT and Mas(-/-) mice, suggesting that endogenous activation of this receptor does not control renal damage under baseline conditions. In conclusion, pharmacological interventions using Mas receptor agonists may represent a therapeutic opportunity for the treatment of renal I/R injury. PMID- 22319646 TI - Neurologic involvement in scleroderma en coup de sabre. AB - Localized scleroderma is a rare disease, characterized by sclerotic lesions. A variety of presentations have been described, with different clinical characteristics and specific prognosis. In scleroderma en coup de sabre (LScs) the atrophic lesion in frontoparietal area is the disease hallmark. Skin and subcutaneous are the mainly affected tissues, but case reports of muscle, cartilage, and bone involvement are frequent. These cases pose a difficult differential diagnosis with Parry-Romberg syndrome. Once considered an exclusive cutaneous disorder, the neurologic involvement present in LScs has been described in several case reports. Seizures are most frequently observed, but focal neurologic deficits, movement disorders, trigeminal neuralgia, and mimics of hemiplegic migraines have been reported. Computed tomography and magnetic resonance imaging have aided the characterization of central nervous system lesions, and cerebral angiograms have pointed to vasculitis as a part of disease pathogenesis. In this paper we describe the clinical and radiologic aspects of neurologic involvement in LScs. PMID- 22319647 TI - Diagnostic disagreements in bipolar disorder: the role of substance abuse comorbidities. AB - Substance abuse can produce symptoms similar to other psychiatric disorders, thus confusing the diagnostic picture. This paper attempts to elucidate how misdiagnosis in bipolar disorder might be explained by the presence of substance abuse comorbidities. The overlap of symptoms, limited information about symptom onset, and inexperienced clinicians can result in the misinterpretation of symptoms of substance abuse disorders for bipolar disorder. The present study found that the presence of a substance abuse comorbidity, the polarity of last episode (depressed, manic, mixed, not otherwise specified), and the total number of comorbidities affected the reliability of a bipolar disorder diagnosis. PMID- 22319648 TI - Antidepressant treatment for acute bipolar depression: an update. AB - While studies in the past have focused more on treatment of the manic phase of bipolar disorder (BD), recent findings demonstrate the depressive phase to be at least as debilitating. However, in contrast to unipolar depression, depression in bipolar patients exhibits a varying response to antidepressants, raising questions regarding their efficacy and tolerability. Methods. We conducted a MEDLINE and Cochrane Collaboration Library search for papers published between 2005 and 2011 on the subject of antidepressant treatment of bipolar depression. Sixty-eight articles were included in the present review. Results. While a few studies did advocate the use of antidepressants, most well-controlled studies failed to show a robust effect of antidepressants in bipolar depression, regardless of antidepressant class or bipolar subtype. There was no significant increase in the rate of manic/hypomanic switch, especially with concurrent use of mood stabilizers. Prescribing guidelines published in recent years rely more on atypical antipsychotics, especially quetiapine, as a first-line therapy. Conclusions. Antidepressants probably have no substantial role in acute bipolar depression. However, in light of conflicting results between studies, more well designed trials are warranted. PMID- 22319649 TI - Physicians' ability to predict hospital length of stay for patients admitted to the hospital from the emergency department. AB - Accurate predictions of patient length of stay (LOS) in the hospital can effectively manage hospital resources and increase efficiency of patient care. A study was done to assess emergency medicine physicians' ability of predicting the LOS of patients who enter the hospital through the ER. Results indicate that EM physicians are relatively accurate with their pediatric patients than any other age groups. In addition, as actual hospital LOS increases, the prediction accuracy decreases. Possible reasons may be due increasing medical complications associated with increasing age and this may lead to overall longer stays. Other variables such as the admitted service of the patient are not statistically significant in predicting LOS in this study. Future studies should be done in order to determine other variables that may affect LOS predictions. PMID- 22319650 TI - Surgical treatment of neuroendocrine liver metastases. AB - Management of Neuroendocrine liver metastases (NELM) is challenging. The presence of NELM worsens survival outcome and almost 10% of all liver metastases are neuroendocrine in origin. There is no firm consensus on the optimal treatment strategy for NELM. A systematic search of the PubMed database was performed from 1995-2010, to collate the current evidence and formulate a sound management algorithm. There are 22 case series with a total of 793 patients who had undergone surgery for NELM. The overall survival ranges from 46-86% at 5 years, 35-79% at 10 years, and the median survival ranges from 52-123 months. After successful cytoreductive surgery, the mean duration of symptom reduction is between 16-26 months, and the 5-year recurrence/progression rate ranges from 59 76%. Five studies evaluated the efficacy of a combination cytoreductive strategy reporting survival rate of ranging from 83% at 3 years to 50% at 10 years. To date, there is no level 1 evidence comparing surgery versus other liver-directed treatment options for NELM. An aggressive surgical approach, including combination with additional liver-directed procedures is recommended as it leads to long-term survival, significant long-term palliation, and a good quality of life. A multidisciplinary approach should be established as the platform for decision making. PMID- 22319651 TI - Hepatic arterial embolization for the treatment of metastatic neuroendocrine tumors. AB - Neuroendocrine tumors (NETs) have a high predilection for metastasizing to the liver and can cause severe debilitating symptoms adversely affecting quality of life. Although surgery remains the treatment of choice, many liver metastases are inoperable at presentation. Hepatic arterial embolization procedures take advantage of the arterial supply of NET metastases. The goals of these therapies are twofold: to increase overall survival by stabilizing tumor growth, and to reduce the morbidity in symptomatic patients. Patients treated with hepatic arterial embolization demonstrate longer progression-free survival and have 5 year survival rates of nearly 30%. The safety of repeat embolizations has also been proven in the setting of recurrent symptoms or progression of the disease. Despite not being curative, hepatic arterial embolization should be used in the management of NETs with liver metastases. Long-term survival is not uncommon, making aggressive palliation of symptoms an important component of treatment. PMID- 22319652 TI - Functional Relationships between Lipid Metabolism and Liver Regeneration. AB - The regenerative capacity of the liver is well known, and the mechanisms that regulate this process have been extensively studied using experimental model systems including surgical resection and hepatotoxin exposure. The response to primary mitogens has also been used to investigate the regulation of hepatocellular proliferation. Such analyses have identified many specific cytokines and growth factors, intracellular signaling events, and transcription factors that are regulated during and necessary for normal liver regeneration. Nevertheless, the nature and identities of the most proximal events that initiate hepatic regeneration as well as those distal signals that terminate this process remain unknown. Here, we review the data implicating acute alterations in lipid metabolism as important determinants of experimental liver regeneration and propose a novel metabolic model of regeneration based on these data. We also discuss the association between chronic hepatic steatosis and impaired regeneration in animal models and humans and consider important areas for future research. PMID- 22319654 TI - Letter from the Editor. PMID- 22319653 TI - Surgical treatment of liver metastases in neuroendocrine neoplasms. AB - Neuroendocrine neoplasms (NENs) are a distinctive entity, and nearly 10% of patients already have liver metastases at presentation. The management of neuroendocrine liver metastases (NEN-LM) is complex with differing patterns of metastatic presentation. An aggressive approach should be used to resect the primary tumor, to remove regional lymph nodes, and to resect or treat appropriate distant metastases (including liver tumors). Despite having an indolent course, NENs have a significantly reduced survival when liver metastases are untreated. Though a wide range of therapies are now available with a multimodal approach to the treatment, surgical treatment offers the only chance for a significant survival prolongation and/or improvement of symptoms and quality of life. A review of the existing surgical modalities for NEN-LM is discussed in this paper. PMID- 22319655 TI - Estrogens in male germ cells. AB - The biosynthesis of steroids and the production of spermatozoa are two major functions of the mammalian testis which are tightly controlled by gonadotropins and numerous locally produced factors. Among these are the estrogens that are produced within the seminiferous epithelium via the irreversible transformation of androgens (C19) into estrogens (C18) by aromatase. We have recently reported that male germ cells are the new source of estrogens in the testis. For instance, estrogen receptors (ER) are found mainly in spermatids that give rise to spermatozoa. Moreover, it is noteworthy that GPR 30 (a transmembrane ER) induces rapid responses after estradiol binding, which, in turn, modulates cyclins and proapoptotic factors (e.g., BAX) to affect germ cell cycle progression and apoptosis. In summary, at least in the animal species that were studied thus far, germ cells are the major source and the target of estrogens, affecting normal male gonadal development and spermatogenesis, in particular spermiogenesis. These findings have also shed new light on the possible adverse effects of endocrine disruptors having estrogenic activities that can cause abnormal development of the male genital tract. PMID- 22319656 TI - Acrosome biogenesis: Revisiting old questions to yield new insights. AB - The acrosome is a unique membranous organelle located over the anterior part of the sperm nucleus that is highly conserved throughout evolution. This acidic vacuole contains a number of hydrolytic enzymes that, when secreted, help the sperm penetrate the egg's coats. Although acrosome biogenesis is an important aspect of spermiogenesis, the molecular mechanism(s) that regulates this event remains unknown. Active trafficking from the Golgi apparatus is involved in acrosome formation, but experimental evidence indicates that trafficking of vesicles out of the Golgi also occurs during acrosomogenesis. Unfortunately, this second aspect of acrosome biogenesis remains poorly studied. In this article, we briefly discuss how the biosynthetic and endocytic pathways, assisted by a network of microtubules, tethering factors, motor proteins and small GTPases, relate and connect to give rise to the sperm-specific vacuole, with a particular emphasis placed on the endosomal compartment. It is hoped that this information will be useful to engage more studies on acrosome biogenesis by focusing attention towards suggested directions. PMID- 22319657 TI - Actin binding proteins and spermiogenesis: Some unexpected findings. AB - Drebrin E, an actin-binding protein lacking intrinsic activity in the regulation of actin dynamics (e.g., polymerization, capping, nucleation, branching, cross linking, bundling and severing), is known to recruit actin regulatory proteins to a specific cellular site. Herein, we critically evaluate recent findings in the field which illustrate that drebrin E works together with two other actin-binding proteins, namely Arp3 (actin-related protein 3, a component of the Arp2/3 complex that simultaneously controls actin nucleation for polymerization and branching of actin filaments) and Eps8 (epidermal growth factor receptor pathway substrate 8 that controls capping of the barbed ends of actin filaments, as well as actin filament bundling) to regulate the homeostasis of F-actin filament bundles at the ectoplasmic specialization (ES), a testis-specific atypical adherens junction (AJ) in the seminiferous epithelium. This is mediated by the strict temporal and spatial expression of these three actin-binding proteins at the apical and basal ES at the Sertoli cell-spermatid (step 8-19) and Sertoli-Sertoli cell interface, respectively, during the seminiferous epithelial cycle of spermatogenesis. In this Commentary, we put forth a possible model by which drebrin E may be acting as a platform upon which proteins (e.g., Arp3) that are needed to alter the conformation of actin filament bundles at the ES can be recruited to the site, thus facilitating changes in cell shape and cell position in the epithelium during spermiogenesis and spermiation. In short, drebrin E may be acting as a "logistic" distribution center to manage different regulatory proteins at the apical ES, thereby regulating the dynamics of actin filament bundles and modulating the plasticity of the apical ES. This would allow adhesion to be altered continuously throughout the epithelial cycle to accommodate spermatid movement in the seminiferous epithelium during spermiogenesis and spermiation. We also describe a hypothetical model, upon which functional studies can be designed in the future. PMID- 22319658 TI - Regulation of blood-testis barrier dynamics by desmosome, gap junction, hemidesmosome and polarity proteins: An unexpected turn of events. AB - The blood-testis barrier (BTB) is a unique ultrastructure in the mammalian testis. Unlike other blood-tissue barriers, such as the blood-brain barrier and the blood-ocular (or blood-retina) barrier which formed by tight junctions (TJ) between endothelial cells of the microvessels, the BTB is constituted by coexisting TJ, basal ectoplasmic specialization (basal ES), desmosomes and gap junctions between adjacent Sertoli cells near the basement membrane of the seminiferous tubule. The BTB also divides the seminiferous epithelium into the apical (or adluminal) and basal compartments so that meiosis I and II and post meiotic germ cell development can all take place in a specialized microenvironment in the apical compartment behind the BTB. While the unusual anatomical features of the BTB have been known for decades, the physiological function of the coexisting junctions, in particular the desmosome and gap junction, that constitute the BTB was unknown until recently. Based on recently published findings, we critically evaluate the role of the desmosome and gap junction that serve as a signaling platform to coordinate the "opening" and "closing" of the TJ-permeability barrier conferred by TJ and basal ES during the seminiferous epithelial cycle of spermatogenesis. This is made possible by polarity proteins working in concert with nonreceptor protein tyrosine kinases, such as focal adhesion kinase (FAK) and c-Src, at the site to regulate endosome mediated protein trafficking events (e.g., endocytosis, transcytosis, recycling or protein degradation). These events not only serve to destabilize the existing "old" BTB above preleptotene spermatocytes in transit in "clones" at the BTB, but also contribute to the assembly of "new" BTB below the transiting spermatocytes. Furthermore, hemidesmosomes at the Sertoli cell-basement membrane interface also contribute to the BTB restructuring events at stage VIII of the epithelial cycle. Additionally, the findings that a gap junction at the BTB provides a possible route for the passage of toxicants [e.g., bisphenol A (BPA)] and potential male contraceptives (e.g., adjudin) across the BTB also illustrate that these coexisting junctions, while helpful to maintain the immunological barrier integrity during the transit of spermatocytes, can be the "gateway" to making the BTB so vulnerable to toxicants and/or chemicals, causing male reproductive dysfunction. PMID- 22319659 TI - Testosterone signaling and the regulation of spermatogenesis. AB - Spermatogenesis and male fertility are dependent upon the presence of testosterone in the testis. In the absence of testosterone or the androgen receptor, spermatogenesis does not proceed beyond the meiosis stage. The major cellular target and translator of testosterone signals to developing germ cells is the Sertoli cell. In the Sertoli cell, testosterone signals can be translated directly to changes in gene expression (the classical pathway) or testosterone can activate kinases that may regulate processes required to maintain spermatogenesis (the non-classical pathway). Contributions of the classical and non-classical testosterone signaling pathways to the maintenance of spermatogenesis are discussed. Studies that may further elaborate the mechanisms by with the pathways support spermatogenesis are proposed. PMID- 22319660 TI - Enhanced chemiluminescence (ECL) for routine immunoblotting: An inexpensive alternative to commercially available kits. AB - Immunoblotting is an analytical technique used by many laboratories to study protein expression. It involves electrophoretic separation of proteins by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), immobilization of these proteins onto a membrane of either nitrocellulose or polyvinylidene difluoride, incubation of the membrane in a monoclonal or polyclonal antibody and detection by a standard method such as enhanced chemiluminescence (ECL). To achieve this, most laboratories opt to use commercially-available chemiluminescence kits which are acceptable but relatively expensive. In this technical report, we show that a self-prepared chemiluminescence reagent is superior to a commercially obtained kit in terms of sensitivity, duration of signal, ease-of-use and shelf-life but at a fraction of the cost of a kit. PMID- 22319662 TI - Testin and actin are key molecular targets of adjudin, an anti-spermatogenic agent, in the testis. AB - Earlier studies have shown adjudin to cause aspermatogenesis by depleting virtually all germ cells from the seminiferous epithelium, leading to transient infertility; spermatogenesis and fertility were re-established several weeks later after germ cell proliferation and differentiation were reinitiated by spermatogonia. While adjudin is known to exert its initial effects at the apical ectoplasmic specialization (a testis-specific atypical anchoring junction), thereby perturbing spermatid adhesion, its molecular target(s) at this site is not known. Herein, we report the production of a specific antibody against adjudin after this compound was conjugated to an adjuvant (i.e., keyhole limpet hemocyanin) to maximize immune response in rabbits. This antibody was utilized for co-immunoprecipitation by using an affinity resin to pull-down the binding partners of adjudin. Using this approach coupled with mass spectrometry and immunoblotting, we show testin (a protein largely restricted to the apical ES in the adult testis) and actin-myosin to be molecular targets of adjudin. These findings provide a platform for future functional studies, not only to better understand the molecular mechanism behind adjudin-induced germ cell loss from the seminiferous epithelium, but also to understand the molecular basis of spermiation. PMID- 22319661 TI - Actin-binding protein drebrin E is involved in junction dynamics during spermatogenesis. AB - The actin-based cytoskeleton plays a critical role in the seminiferous epithelium during spermatogenesis by conferring cell shape, adhesion, structural support and cell polarity to both Sertoli and developing germ cells, which are essential for spermatogonial stem cell renewal, maintenance of the stem cell niche, cell cycle progression, mitosis, meiosis, spermiogenesis and spermiation. However, few functional studies are found in the literature, which explore the functional significance of actin dynamics in these events. This by and large is due to a lack of information on the proteins that regulate actin dynamics. Herein, we report drebrin E is an integrated component of the apical ectoplasmic specialization (apical ES) and the basal ES at the blood-testis barrier (BTB) in the seminiferous epithelium of the adult rat testis. Using immunohistochemistry and dual-labeled immunofluorescence analysis, drebrin E was found to display a stage-specific localization at the apical ES, as well as at the basal ES at the BTB during the seminiferous epithelial cycle of spermatogenesis. Drebrin E was first detected in stage V tubules at the basal ES with the highest expression at the BTB at stages V and VI, but it diminished considerably by stages VII and VIII and was almost non-detectable until stage IV. At the apical ES, drebrin E was also first detected at stage V, surrounding the entire head of the elongating spermatid, but by stage VI its localization had "shifted" to localize most intensely and almost exclusively to the concave side of the spermatid head. In stage VII tubules, drebrin E co-localized with actin, as well as with two other actin regulatory proteins Eps8 (epidermal growth factor receptor pathway substrate 8, an actin capping and bundling protein) and Arp3 (actin-related protein 3, a component of the Arp2/3 complex known to regulate actin nucleation and branching). The localization of drebrin E at the apical ES was compromised following treatment of rats with adjudin, which is known to exert its destructive effects primarily at the apical ES by inducing premature loss of elongating/elongated spermatids from the epithelium, mimicking "spermiation." Instead of being restricted to the concave side of spermatid heads, drebrin E was found to be mis-localized in the seminiferous epithelium of adjudin-treated rats; it was also present on the convex side of elongating spermatids, but these cells were mis-oriented so that their heads no longer pointed toward the basement membrane. The expression of drebrin E by Sertoli cells was also found to be modulated by TGFbeta3 and TNFalpha. Since Arp3, but not Eps8, was found to bind drebrin E; and cytokines were also shown to affect the cellular distribution of drebrin E and enhance the interaction between drebrin E and Arp3, these findings illustrate that cytokines may regulate BTB dynamics during the epithelial cycle by recruiting drebrin E and Arp3 to the BTB microenvironment to induce changes in the configuration of actin filament bundles at the basal ES. In summary, these findings illustrate drebrin E is working in concert with Arp3 to regulate actin filament bundles at both the apical and the basal ES in the testis, conferring adhesion and cell polarity at both sites during spermatogenesis. PMID- 22319663 TI - Characterization of the porcine testis-expressed gene 11 (Tex11). AB - Testis expressed gene 11 (Tex11) is essential for meiosis and male fertility in the mouse. Currently, little is known about the control of spermatogenesis in non rodent animal models such as pigs. Here, we characterized the sequence and expression profile of the porcine Tex11 gene. We showed that the porcine Tex11 is an X-linked gene that is exclusively expressed in germ cells in the adult pig testis. The expression of porcine Tex11 is correlated with the onset of meiosis and the expression pattern is highly conserved between the Tex11 homologs in pig and mouse. The DNA sequence analysis and the estimated molecular weight also suggested a high level of homology across species. As the mouse Tex11 proved to be essential for male fertility, the important biological function during meiosis is likely conserved in the porcine Tex11. PMID- 22319664 TI - Expression of Itch in Sertoli cells is controlled via the interaction of E2F1/DP1 complex with E2F and GATA motifs. AB - Itch, an ubiquitin E3 ligase, has been implicated in the regulation of the permeability of tight junction (TJ) barriers in Sertoli cells. It is involved in cAMP-mediated TJ disruption by targeting occludin for proteasomal degradation in the testis. However, the molecular mechanisms governing its transcription remain enigmatic. By the transient transfection of Itch promoter luciferase construct in TM4 cells, we showed that the minimal Itch promoter was located between nucleotides -151 and -1 (relative to the translation start site). One E2F motif and two each of GATA and Nkx motifs were identified within the core promoter region. Mutation and overexpression analyses have shown that the E2F and GATA-a motifs are involved in Itch gene transcription, but play different roles. The E2F motif is the crucial cis-acting element that drives the basal gene transcription, while the GATA-a motif functionally co-operates with E2F motif. By electromobility shift assays, we confirmed that E2F1 and DP1 form heterodimers and binds to E2F and GATA-a motifs. Taken together, the GATA-a motif assists/strengthens the binding of E2F1/DP1 complex to the E2F motif, resulting in efficient looping of promoter region of Itch gene for transcription. PMID- 22319665 TI - The effects of glutathione, insulin and oxidative stress on cultured spermatogenic cysts. AB - Spermatogenesis is a series of cellular processes that leads to the development of motile, elongate sperm cells. Mitotic expansion of spermatogenic stem cells is followed by two meiotic cell divisions that yield haploid round spermatids which then transform from a spherical form into an elongate, highly polarized form. In Drosophila, spermatogenesis takes place within encapsulating cysts that contain spermatogenic cells. Spermatogenic cysts were isolated and grown in culture over the course of 96 hours. Cultures were treated with buthionine sulfoximine (BSO), glutathione (GSH), insulin and GSH+insulin in order to test the effects of these agents on cyst viability. The addition of glutathione and exogenous insulin to cultured spermatogenic cysts each appeared to have a positive effect on early spermatogenic cyst survival in vitro at some timepoints. The addition of GSH+insulin together had no significant effect on early spermatogenic cyst survival in vitro. Oxidative stress induced by BSO resulted in a significant decrease and/or complete loss of specific early spermatogenic cyst types and the abnormal development of elongating cysts in culture. This culture system offers the opportunity for high-resolution analysis of spermatogenic processes not previously possible. PMID- 22319666 TI - Interactions of laminin beta3 fragment with beta1-integrin receptor: A revisit of the apical ectoplasmic specialization-blood-testis-barrier-hemidesmosome functional axis in the testis. AB - Recent studies have demonstrated the presence of a functional axis that coordinates the events of spermiation and blood-testis barrier (BTB) restructuring which take place simultaneously at the opposite ends of the seminiferous epithelium at stage VIII of the epithelial cycle of spermatogenesis in the rat testis. In short, the disruption of the apical ectoplasmic specialization (apical ES) at the Sertoli cell-elongated spermatid interface, which facilitates the release of sperm at spermiation near the tubule lumen, is coordinated with restructuring at the BTB to accommodate the transit of preleptotene spermatocytes across the immunological barrier near the basement membrane. These two events are likely coordinated by a functional axis involving hemidesmosome at the Sertoli cell-basement membrane interface, and it was designated the apical ES-BTB-hemidesmosome axis. It was demonstrated that fragments of laminin chains (e.g., laminin beta3 or gamma3 chains) derived from the alpha6beta1-integrin-laminin333 protein complex at the apical ES, which were likely generated via the action of MMP-2 (matrix metalloprotease-2, MMP2) prior to spermiation, acted as biologically active peptides to perturb the BTB permeability function by accelerating protein endocytosis (e.g., occludin) at the site, thereby destabilizing the BTB integrity to facilitate the transit of preleptotene spermatocytes. These laminin fragments also perturbed hemidesmosome function via their action on beta1-integrin, a component of hemidesmosome in the testis, which in turn, sent a signal to further destabilize the BTB function. As such, the events of spermiation and BTB restructuring are coordinated via this functional axis. Recent studies using animal models treated with toxicants, such as mono-(2-ethylhexyl) phthalate (MEHP), or adjudin, a male contraceptive under investigation, have also supported the presence of this functional axis in the mouse. In this short review, we critically evaluate the role of this local functional axis in the seminiferous epithelium in spermatogenesis. We also provide molecular modeling information on the interactions between biologically active laminin fragments and beta1-integrin, which will be important to assist in the design of more potent laminin-based peptides to disrupt this axis, thereby perturbing spermatogenesis for male contraception and to understand the underlying biology that coordinates spermiation and BTB restructuring during spermatogenesis. PMID- 22319667 TI - c-kit and its related genes in spermatogonial differentiation. AB - Spermatogenesis is the process of production of male gametes from SSCs. The SSCs are the stem cells that differentiate into male gametes in the testis. in the mean time, the Spg are remarkable for their potential multiple trans differentiations, which make them greatly invaluable for clinical applications. However, the molecular mechanism controlling differentiation of the Spg is still not clear. Among the discovered spermatogenesis-related genes, c-kit seems to be expressed first by the Spgs thus may play a central role in switching on the differentiation process. Expression of Kit and the activation of the Kit/Kitl pathway coincide with the start of differentiation of Spgs. Several genes have been discovered to be related to the Kit/Kitl pathway. in this review, we have summarized the recent discoveries of c-kit and the Kit/Kitl pathway-related genes in the spermatogenic cells during different stages of spermatogenesis. PMID- 22319668 TI - The emerging role of matrix metalloproteases of the ADAM family in male germ cell apoptosis. AB - Constitutive germ cell apoptosis during mammalian spermatogenesis is a key process for controlling sperm output and to eliminate damaged or unwanted cells. An increase or decrease in the apoptosis rate has deleterious consequences and leads to low sperm production. Apoptosis in spermatogenesis has been widely studied, but the mechanism by which it is induced under physiological or pathological conditions has not been clarified. We have recently identified the metalloprotease ADAM17 (TACE) as a putative physiological inducer of germ cell apoptosis. The mechanisms involved in regulating the shedding of the ADAM17 extracellular domain are still far from being understood, although they are important in order to understand cell-cell communications. Here, we review the available data regarding apoptosis during mammalian spermatogenesis and the localization of ADAM proteins in the male reproductive tract. We propose an integrative working model where ADAM17, p38 MAPK, protein kinase C (PKC) and the tyrosine kinase c-Abl participate in the physiological signalling cascade inducing apoptosis in germ cells. In our model, we also propose a role for the Sertoli cell in regulating the Fas/FasL system in order to induce the extrinsic pathway of apoptosis in germ cells. This working model could be applied to further understand constitutive apoptosis in spermatogenesis and in pathological conditions (e.g., varicocele) or following environmental toxicants exposure (e.g., genotoxicity or xenoestrogens). PMID- 22319670 TI - Cytoskeletal track selection during cargo transport in spermatids is relevant to male fertility. AB - Spermatids generate diverse and unusual actin and microtubule populations during spermiogenesis to fulfill mechanical and cargo transport functions assisted by motor and non-motor proteins. Disruption of cargo transport may lead to teratozoospermia and consequent male infertility. How motor and non-motor proteins utilize the cytoskeleton to transport cargos during sperm development is not clear. Filamentous actin (F-actin) and the associated motor protein myosin Va participate in the transport of Golgi-derived proacrosomal vesicles to the acrosome and along the manchette. The acrosome is stabilized by the acroplaxome, a cytoskeletal plate anchored to the nuclear envelope. The acroplaxome plate harbors F-actin and actin-like proteins as well as several other proteins, including keratin 5/Sak57, Ran GTPase, Hook1, dynactin p150Glued, cenexin-derived ODF2, testis-expressed profilin-3 and profilin-4, testis-expressed Fer tyrosine kinase (FerT), members of the ubiquitin-proteasome system and cortactin. Spermatids express transcripts encoding the non-spliced form of cortactin, a F actin-regulatory protein. Tyrosine phosphorylated cortactin and FerT coexist in the acrosome-acroplaxome complex. Hook1 and p150Glued, known to participate in vesicle cargo transport, are sequentially seen from the acroplaxome to the manchette to the head-tail coupling apparatus (HTCA). The golgin Golgi microtubule associated protein GMAP210 resides in the cis-Golgi whereas the intraflagellar protein IFT88 localizes in the trans-Golgi network. Like Hook1 and p150Glued, GMAP210 and IFT88 colocalize at the cytosolic side of proacrosomal vesicles and, following vesicle fusion, become part of the outer and inner acrosomal membranes before relocating to the acroplaxome, manchette and HTCA. A hallmark of the manchette and axoneme is microtubule heterogeneity, determined by the abundance of acetylated, tysosinated and glutamylated tubulin isoforms produced by post-translational modifications. We postulate that the construction of the male gamete requires microtubule and F-actin tracks and specific molecular motors and associated non-motor proteins for the directional positioning of vesicular and non-vesicular cargos at specific intracellular sites. PMID- 22319669 TI - Cancer/testis (CT) antigens, carcinogenesis and spermatogenesis. AB - During spermatogenesis, spermatogonial stem cells, undifferentiated and differentiated spermatogonia, spermatocytes, spermatids and spermatozoa all express specific antigens, yet the functions of many of these antigens remain unexplored. Studies in the past three decades have shown that many of these transiently expressed genes in developing germ cells are proto-oncogenes and oncogenes, which are expressed only in the testis and various types of cancers in humans and rodents. As such, these antigens are designated cancer/testis antigens (CT antigens). Since the early 1980s, about 70 families of CT antigens have been identified with over 140 members are known to date. Due to their restricted expression in the testis and in various tumors in humans, they have been used as the target of immunotherapy. Multiple clinical trials at different phases are now being conducted with some promising results. Interestingly, in a significant number of cancer patients, antibodies against some of these CT antigens were detected in their sera. However, antibodies against these CT antigens in humans under normal physiological conditions have yet to be reported even though many of these antigens are residing outside of the blood-testis barrier (BTB), such as in the basal compartment of the seminiferous epithelium and in the stem cell niche in the testis. In this review, we summarize latest findings in the field regarding several selected CT antigens which may be intimately related to spermatogenesis due to their unusual restricted expression during different discrete events of spermatogenesis, such as cell cycle progression, meiosis and spermiogenesis. This information should be helpful to investigators in the field to study the roles of these oncogenes in spermatogenesis. PMID- 22319671 TI - Endocrine disrupting chemicals: Multiple effects on testicular signaling and spermatogenesis. AB - In the past 200 years, an enormous number of synthetic chemicals with diverse structural features have been produced for industrial, medical and domestic purposes. These chemicals, originally thought to have little or no biological toxicity, are widely used in our daily lives as well as are commonly present in foods. It was not until the first World Wildlife Federation Wingspread Conference held in 1994 were concerns about the endocrine disrupting (ED) effects of these chemicals articulated. The potential hazardous effects of endocrine disrupting chemicals (EDCs) on human health and ecological well-being are one of the global concerns that affect the health and propagation of human beings. Considerable numbers of studies indicated that endocrine disruption is linked to "the developmental basis of adult disease," highlighting the significant effects of EDC exposure on a developing organism, leading to the propensity of an individual to develop a disease or dysfunction in later life. In this review, we intend to provide environmental, epidemiological and experimental data to associate pollutant exposure with reproductive disorders, in particular on the development and function of the male reproductive system. Possible effects of pollutant exposure on the processes of embryonic development, like sex determination and masculinization are described. In addition, the effects of pollutant exposure on hypothalamus-pituitary-gonadal axis, testicular signaling, steroidogenesis and spermatogenesis are also discussed. PMID- 22319672 TI - Teasing out the role of aromatase in the healthy and diseased testis. AB - Scientific discoveries over the past decade have shifted the stereotypical view of androgens as male hormones and estrogens as female hormones. It is now recognized that a delicate balance of both androgens and estrogens, a process controlled by aromatase, is fundamental for normal testicular development and fertility. While the site-specific actions of these two classes of steroids within the testis are becoming better documented, the role and regulation of estrogen biosynthesis by aromatase within the testis remains unclear. The majority of data comes from a wide range of animal species, particularly genetically modified mouse models; aromatase knockout (ArKO) and overexpressing (AROM(+)), with limited information on humans, however the existence of congenital aromatase mutations has provided some insight into its effects on individual parameters of the testis. This review dissects out the localization and activity of aromatase in the healthy and diseased testis, addresses the cellular insult to the testis that occurs in its absence and over abundance and proposes potential molecular mechanisms of aromatase regulation in the testis. PMID- 22319673 TI - Reptilian spermatogenesis: A histological and ultrastructural perspective. AB - Until recently, the histology and ultrastructural events of spermatogenesis in reptiles were relatively unknown. Most of the available morphological information focuses on specific stages of spermatogenesis, spermiogenesis, and/or of the mature spermatozoa. No study to date has provided complete ultrastructural information on the early events of spermatogenesis, proliferation and meiosis in class Reptilia. Furthermore, no comprehensive data set exists that describes the ultrastructure of the entire ontogenic progression of germ cells through the phases of reptilian spermatogenesis (mitosis, meiosis and spermiogenesis). The purpose of this review is to provide an ultrastructural and histological atlas of spermatogenesis in reptiles. The morphological details provided here are the first of their kind and can hopefully provide histological information on spermatogenesis that can be compared to that already known for anamniotes (fish and amphibians), birds and mammals. The data supplied in this review will provide a basic model that can be utilized for the study of sperm development in other reptiles. The use of such an atlas will hopefully stimulate more interest in collecting histological and ultrastructural data sets on spermatogenesis that may play important roles in future nontraditional phylogenetic analyses and histopathological studies in reptiles. PMID- 22319674 TI - A study to assess the assembly of a functional blood-testis barrier in developing rat testes. AB - The blood-testis barrier (BTB) is an important ultrastructure in the seminiferous tubule of the mammalian testis that segregates the events of spermatogenesis, in particular post-meiotic germ cell development, from the harmful substances in the environment including toxicants and drugs, as well as from the unwanted hormones and biomolecules in the systemic circulation. It is known that the BTB is assembled by ~15-21 days postpartum (dpp) in rats coinciding with the onset of late cell cycle progression, namely the formation of zygotene and pachytene spermatocytes by day 15-18 dpp. This is to prepare for: (1) the differentiation/transformation of pachytene spermatocytes to diplotene and dictyate spermatocytes and (2) meiosis I and II, which take place by 23-26 and 26 dpp, respectively. Recent findings have shown spermatogonia/spermatogonial stem cells (SSC) in the tubules failed to re-initiate spermatogenesis by differentiating spermatogonia beyond type A spermatogonia in the absence of a functional BTB, leading to meiotic arrest. These studies thus illustrate that a functional BTB is crucial to the initiation and/or re-initiation of spermatogenesis. Herein, we sought to examine the precise time window when a functional and intact BTB is established in the developing rat testis during the final stage of cell cycle progression and meiosis. Using the techniques of: (1) dual-labeled immunofluorescence analysis to assess the distribution of integrated proteins at the tight junction (TJ), basal ectoplasmic specialization [basal ES, a testis-specific atypical adherens junction (AJ) type] and gap junction (GJ) at the BTB, (2) functional assay to assess the BTB integrity in vivo, (3) immunoblot analysis to monitor changes in steady-state levels of adhesion proteins at the BTB, and (4) co-immunoprecipitation to assess changes in protein-protein interactions at the BTB, it was shown that a BTB was being assembled by day 15-20 dpp, but a functional BTB was not fully established until day 25 dpp in Sprague Dawley rats, tightly associated with the onset of meiosis I and II. These findings thus illustrate the significance of the BTB on cell cycle progression and the preparation for meiosis, such as germ cell differentiation beyond type A spermatogonia. PMID- 22319675 TI - Development of Secreted Protein and Acidic and Rich in Cysteine (SPARC) Targeted Nanoparticles for the Prognostic Molecular Imaging of Metastatic Prostate Cancer. AB - Prostate cancer is the most commonly diagnosed non-skin malignancy in the United States and presents with a wide range of aggressiveness from extremely slow growing to highly aggressive. There is a clinical need to determine the metastatic potential of the primary tumor to design the most appropriate treatment plan ranging from watchful waiting to more aggressive, invasive surgical treatments. In this study we have developed a nanoparticle based imaging agent that targets SPARC (Secreted Protein Acidic Rich in Cysteine), a molecular marker of prostate cancer metastatic potential. Previous studies by this group used phage display to identify a peptide with high binding affinity and specificity for SPARC. In this study, the SPARC-targeted peptide sequence was used to design a biomaterial with improved pharmacokinetic properties by attaching it to a biocompatible nanoparticle that is also coupled to a fluorophore for in vivo imaging. Prostate cancer cell lines with varying degrees of SPARC expression were used to show the ability of the targeted nanoparticle to bind specifically to SPARC in vitro and in vivo including the clinically relevant bone and lung metastases. We show that in vivo imaging information correlates with the metastatic potential of the prostate tumor. This prognostic information could enable doctors to stratify patients and design personalized treatment strategies. PMID- 22319676 TI - The influence of core musculature engagement on hip and knee kinematics in women during a single leg squat. AB - PURPOSE/BACKGROUND: Excessive frontal plane motion and valgus torques have been linked to knee injuries, particularly in women. Studies have investigated the role of lower extremity musculature, yet few have studied the activation of trunk or "core" musculature on hip and knee kinematics. Therefore, this study evaluated the influence of intentional core engagement on hip and knee kinematics during a single leg squat. METHODS: Participants (n = 14) performed a single leg squat from a 6 inch step under 2 conditions: core intentionally engaged (CORE) and no intentional core engagement (NOCORE). Participants were also evaluated for core activation ability using Sahrmann's model, and the resulting scores were used to divide participants into low (LOWCORE) and high scoring (HIGHCORE) groups. All trials were captured using 3-D motion analysis, and data were normalized for height and time. Paired t-tests and repeated measures, mixed model MANOVAs were used to assess condition and group differences. RESULTS: The CORE condition, compared to NOCORE, was characterized by smaller right [t(13) = 3.03, p = .01] and left [t(13) = 3.04, p = .01] hip frontal plane displacement and larger knee flexion range of motion [t(13) = 3.08, p = .009]. Subsequent MANOVAs and follow up analyses revealed that: (1) the CORE condition demonstrated smaller right and left hip medial-lateral displacement in the LOWCORE group (p = .001), but not in the HIGHCORE group; (2) the CORE condition showed larger overall knee flexion range of motion across LOWCORE and HIGHCORE groups (p = .021); and (3) the HIGHCORE group exhibited less knee varus range of motion across CORE and NOCORE conditions (p = .028). CONCLUSIONS: Intentional core activation influenced hip and knee kinematics during single leg squats, with greater positive effect noted in the LOWCORE group. These findings may have implications for preventing and rehabilitating knee injuries among women. LEVEL OF EVIDENCE: 2B, Cohort laboratory study, mixed model design. PMID- 22319677 TI - Lateral abdominal muscle symmetry in collegiate single-sided rowers. AB - PURPOSE/BACKGROUND: Although side to side symmetry of lateral abdominal muscle thickness has been established in healthy individuals, it is unknown whether abdominal muscle symmetry exists in athletes with asymmetrical physiological demands, such as those of single-sided rowers. The purpose of this study was to examine the oarside versus the non-oarside lateral abdominal musculature thickness in collegiate single-sided rowers, as measured by ultrasound imaging (USI). METHODS: The study was a prospective, cross-sectional, observational design. Thirty collegiate crew team members (17 males, 13 females, age 19.8+/-1.2 years) characterized as single-sided rowers participated. Resting muscle thickness measurements of the transversus abdominis (TrA), internal oblique (IO), and external oblique (EO) muscles were obtained via USI. Comparisons of absolute and relative muscle thickness between oarside and non-oarside were performed using paired t-tests. Potential differences based on gender, rowing experience, and history of low back pain were investigated using mixed model analysis of variance. RESULTS: There were no clinically significant differences in absolute or relative thickness of the TrA, IO or EO on the oarside versus the non-oarside. There were no significant side to side differences in the relative muscle thickness of the TrA, IO or EO based on gender, rowing experience, or history of low back pain. CONCLUSIONS: In this sample of single-sided rowing athletes, no clinically significant side to side differences in lateral abdominal muscle thickness were observed. Despite the asymmetrical functional demands of single sided rowers in this study, thickness of the lateral abdominal muscles was symmetric. LEVEL OF EVIDENCE: 4. PMID- 22319678 TI - A randomized trial of isokinetic versus isotonic rehabilitation program after arthroscopic meniscectomy. AB - BACKGROUND: Although both isotonic and isokinetic exercises are commonly used in the rehabilitation of patients after arthroscopic meniscectomy no studies have compared their effect on strength recovery and functional outcomes. PURPOSE: The purpose of this study was to investigate the effects of two rehabilitation programs (isotonic and isokinetic) on muscle strength and functional performance after partial knee meniscectomy. A secondary purpose was to assess the correlation between isokinetic strength deficits and hop test performance deficits. METHODS: Twenty male patients who underwent arthroscopic partial meniscectomy volunteered for the study. Both isotonic and isokinetic training were performed with the same equipment thereby blinding subjects to the mode of exercise. Main outcome measures were collected on the 14th and 33rd postoperative days and included isokinetic strength of the knee extensors and flexors, functional performance (single, triple, and vertical hopping) and the Lysholm questionnaire. Multivariate and univariate analyses of variance were used to assess the effects of the independent variables on the isokinetic variables, functional tests, and Lysholm score. Pearson's correlation was used to assess the relationship between isokinetic strength deficits and functional performance deficits. RESULTS: Isokinetic measures, functional tests, and the Lysholm score all increased between initial and final assessment (p<=0.003). However, there were no group or group*time effects on any of the outcome variables (p>=0.33). Functional tests were better predictors of isokinetic deficits in the 14(th) compared to the 33(rd) postoperative day. CONCLUSION: No differences were found in the outcomes of patients treated using an isokinetic and an isotonic protocol for rehabilitation after arthroscopic meniscectomy. More than half of patients did not meet the 90% criterion in the hop tests for safe return to sports five weeks after meniscectomy. There were correlations between the hop tests and isokinetic deficits two weeks after meniscectomy but not at the fifth week. LEVEL OF EVIDENCE: 1b. PMID- 22319679 TI - A novel technique for determining scapulohumeral translation: a case-control and inter-rater reliability study. AB - BACKGROUND: Alterations in scapular and glenohumeral kinematics in patients with shoulder dysfunction have been recognized by this studies authors' and described in multiple other studies available in the literature. A reliability study was developed to assess a new technique for measuring scapulohumeral kinematics. Previous scapular position measuring techniques may require expensive equipment which decreases clinical utility. Other techniques require identification of multiple anatomic landmarks that may decrease accuracy, precision, and reliability. METHODS: A sample of asymptomatic controls and symptomatic study subjects were recruited. Each subject had markers placed on each acromion and stood at a standardized distance in front of a light. The shadow projected from the acromial marker onto a standardized, data collection board was measured during the resting, flexion, and scaption positions for bilateral shoulders. The horizontal and vertical translations of the shadows were measured compared to the resting point for both flexion and scaption. RESULTS: The scapula translated superiorly and medially during both flexion and scaption movements in all subjects and controls. There was good inter-rater reliability for measuring scapular translation with scaption (ICC= 0.81) and moderate reliability for measuring scapular translation with flexion (ICC = 0.62). There was increased superior and medial scapular translation in the subjects with flexion (p= 0.004 and p=0.002) and scaption (p= 0.01 and p=0.007) in the symptomatic shoulder compared to the asymptomatic shoulder. Superior scapular translation with flexion (p=0.0003) and scaption (p=0.006) and medial scapular translation with flexion (p<0.0001) and scaption (p<0.0001) was greater in the symptomatic subjects compared to controls. CONCLUSIONS: The scapula translates both superiorly and medially with flexion and scaption in asymptomatic and symptomatic subjects. After shoulder surgery, patients have increased superior and medial translation of the scapula compared to 1) their asymptomatic shoulder and 2) an asymptomatic control group. The current technique has good inter-rater reliability (ICC=0.81) when measuring scaption and moderate reliability when measuring flexion (ICC=0.62). LEVEL OF EVIDENCE: III Diagnostic Case-Control Study. PMID- 22319680 TI - Muscle activation of the torso during the modified razor curl hamstring exercise. AB - PURPOSE/BACKGROUND: The RAZOR curl has been introduced as a hamstring exercise. However, modifications to the exercise have been developed which are proposed to utilize some of the muscles of the lumbo-pelvic-hip complex. Thus, it was the purpose of this study to quantitatively examine the modified RAZOR curl using surface electromyography (sEMG), as an exercise that may recruit the trunk muscles of the lumbo-pelvic-hip complex. METHODS: Twenty-eight active male and female graduate students (24.2+/-1.3 years; 174.8+/-9.9 cm; 74.9+/-14.9 kg), consented to participate. Dependent variables were muscle activation of trunk musculature (dominant side gluteus medius, gluteus maximus, multifidus, longissimus, lower rectus abdominis, upper rectus abdominis, external obliques) reported as percent of maximum voluntary isometric contraction (%MVIC) during the exercise while the independent variable was the muscle selected. RESULTS: The multifidus and longissimus demonstrated moderately strong activation (35-50%MVIC) while the upper rectus abdominis demonstrated strong activation (20-35%MVIC) and the gluteus medius, gluteus maximus, lower rectus abdominis, and external obliques had minimal activation. CONCLUSIONS: These findings allow the practitioner to utilize an exercise that provides a functional training stimulus that activates not only the hamstrings but also some musculature of the trunk muscles of the lumbopelvic-hip complex at strong to moderately strong levels. LEVEL OF EVIDENCE: 5. PMID- 22319681 TI - The victorian institute of sports assessment - achilles questionnaire (visa-a) - a reliable tool for measuring achilles tendinopathy. AB - BACKGROUND: Achilles tendinopathy (AT) is a common pathology and the aetiology is unknown. For valid and reliable assessment The Victorian Institute of Sports Assessment has designed a self-administered Achilles questionnaire, the VISA-A. The aim of the present study was to evaluate VISA-A as an outcome measure in patients with AT. METHODS: A systematic search of the literature was conducted using MEDLINE, EMBASE, CINAHL, PEDro, Web of Science, and Cochrane Controlled trials to identify trials using VISA-A for patients with AT. This was followed by data mining and analysis of the obtained data. RESULTS: Twenty-six clinical trials containing 1336 individuals were included. Overall mean VISA-A scores ranged from 24 (severe AT) to 100 (healthy). Mean VISA-A scores in patients with AT ranged from 24 to 96.6. Healthy subjects scored a minimum of 96. Only two groups of participants from two different studies had a post-VISA-A score as high as healthy individuals, indicating full recovery of the AT. CONCLUSIONS: A VISA-A score lower than 24 is rarely attained in AT. Only few patients with AT reach an equivalent VISA-A score compared to uninjured healthy subjects following treatment. The VISA-A is a reliable tool when assessing AT patients, providing a good assessment of the actual condition from very poor, (score around 24) to excellent (a score of 90), which based on this systematic review and previous studies could be considered full recovery from AT. PMID- 22319682 TI - Non-surgical treatment of a professional hockey player with the signs and symptoms of sports hernia: a case report. AB - STUDY DESIGN: Case Report BACKGROUND: Injury or weakness of lower abdominal attachments and the posterior inguinal wall can be symptoms of a "sports hernia" and an underlying source of groin pain. Although several authors note conservative treatment as the initial step in the management of this condition, very little has been written on the specific description of non-surgical measures. Most published articles favoring operative care describe poor results related to conservative management; however they fail to report what treatment techniques comprise non-operative management. CASE PRESENTATION: The subject of this case report is a professional ice hockey player who sustained an abdominal injury in a game, which was diagnosed as a sports hernia. Following the injury, structured conservative treatment emphasized core control and stability with progressive peripheral demand challenges. Intrinsic core control emphasis continued throughout the treatment progression and during the functional training prior to return to sport. OUTCOME: The player completed his recovery with return to full competition seven weeks post injury, and continues to compete in the NHL seven years later. DISCUSSION: Surgical intervention has been shown to be effective in the treatment of the "sports hernia." However it is the authors' opinion that conservative care emphasizing evaluation of intrinsic core muscular deficits and rehabilitation directed at addressing these deficits is an appropriate option, and should be considered prior to surgical intervention. PMID- 22319683 TI - Low back pain in a competitive cricket athlete. AB - Physical therapists treating adolescent and young adult athletes with low back pain complaints should have a high level of clinical suspicion of the possibility for spondylolysis, spondylolisthesis, or developing stress reactions of the pars interarticularis. This case outlines the use of conventional radiography, computerized tomography, and Single photon emission computed tomography (SPECT) in the differential diagnosis for an adolescent cricket athlete with low back pain. PMID- 22319684 TI - Current concepts in muscle stretching for exercise and rehabilitation. AB - Stretching is a common activity used by athletes, older adults, rehabilitation patients, and anyone participating in a fitness program. While the benefits of stretching are known, controversy remains about the best type of stretching for a particular goal or outcome. The purpose of this clinical commentary is to discuss the current concepts of muscle stretching interventions and summarize the evidence related to stretching as used in both exercise and rehabilitation. PMID- 22319685 TI - Are all physical therapists qualified to provide sideline coverage of athletic events? AB - The new graduate, or the licensed physical therapist with general orthopedic experience, is not qualified to provide sideline coverage at athletic events. Additional or advanced training in emergency care is essential to provide aid in acute situations. Completion of the First Responder certification prepares an individual to react appropriately to any emergency on the sidelines, in the clinic, or in the community. The highest qualification that a physical therapist can attain to ensure adequate preparation for the practice of Sports Physical therapy is the ABPTS Sports Certified Specialist (SCS) designation. This professional designation indicates that this individual is highly qualified to care for athletes at any level, from on the sidelines, through rehabilitation and return to play, regardless of the injury, age of the athlete, or skill level. PMID- 22319687 TI - The location of maxillary sinus ostium and its clinical application. AB - The endoscopic sinus surgeons must have a detailed knowledge of inconsistent location of maxillary sinus openings in any interventional maxillary sinus surgeries as it relates to the orbital floor, ethmoid infundibulum and the nasolacrimal duct. Forty cadaver head and neck specimens had been cut sagittally through the nose, such that the lateral nasal wall had been preserved. The findings were documented with an emphasis on location of the maxillary sinus openings. In the present study maxillary sinus ostium opened more commonly into posterior third of the hiatus semilunaris. Accessory maxillary ostium was another variation seen in nearly three-fourths of the cases which opened into membranous meatus inferior to the uncinate process. PMID- 22319686 TI - Elevated DISC1 transcript levels in PBMCs during acute psychosis in patients with schizophrenia. AB - BACKGROUND: Severe mental disorders like schizophrenia are a leading cause of disability in people in the prime years of their lives (aged 15 to 44 years). Relapse is a primary contributor to schizophrenia disease burden and is frequently attributed to medication noncompliance and inadequate doses. Currently, a patient's neuroleptic dose is titrated to clinical response within recommended dose ranges. Use of unbiased biomarkers of effective neuroleptic treatment-response would greatly facilitate the identification of a person's lowest effective dose to minimize unsafe side effects and improve compliance. Biomarkers may allow precisely tailored adjustments of neuroleptic dose to reduce relapse due to variable disease course. METHODS AND FINDINGS: Biomarkers of active psychosis were sought among persons with schizophrenia hospitalized with acute psychosis. The transcriptional response of peripheral blood mononuclear cells (PBMCs) to treatment of psychosis was measured using RNA expression profiling in 12-paired samples from patients with schizophrenia. The paired samples were collected early after treatment initiation and again just before patients were released from the hospital. Patients showed significant improvement in positive symptoms of psychosis assessed at each sample collection using a brief psychiatric rating scale (BPRS) (P<0.05). Preliminary evidence is presented indicating that decreased transcript levels of isoforms of disrupted in schizophrenia 1 (DISC1) measured in PBMCs were associated with treatment in 91% of samples (P=0.037). CONCLUSION: Further studies are warranted to identify neuroleptic-response biomarkers and to replicate this initial finding of association of DISC1 transcript levels with treatment of psychosis. PMID- 22319688 TI - Accuracy of references in Indian journal of otolaryngology and head & neck surgery. AB - This study was done to observe the accuracy of references in articles published in Indian Journal of Otolaryngology and Head & Neck Surgery. There were 63 references randomly selected from different issues of Indian Journal of Otolaryngology and Head & Neck Surgery (IJOHNS). It includes: Volume 61, Number 4, December 2009 and Volume 62, Number 1, January 2010. References were examined in details by dividing them into six elements and they were compared with the original for accuracy. References not cited from indexed journals were excluded. Statistical analysis was done by using frequency and percentage. Results show that 30.1% references in Indian Journal of Otolaryngology and Head & Neck Surgery were incorrect. Most common errors were author's name and journal name. Author's names were found to be incorrect in 11.1% references while journal name were found to be incorrect in 6.3%. Errors in citing the references are also found in the Indian Journal of Otolaryngology and Head & Neck Surgery. The quoted error in this study is comparable to other international literatures. The majority of errors are avoidable. So, the authors, editors and the reviewers have to check for any errors seriously before publication in the journal. PMID- 22319689 TI - Speech recognition performance in children with cochlear implants using bimodal stimulation. AB - Cochlear implantees have considerably good speech understanding abilities in quiet surroundings. But, ambient noise poses significant difficulties in understanding speech for these individuals. Bimodal stimulation is still not used by many Indian implantees in spite of reports that bimodal stimulation is beneficial for speech understanding in noise as compared to cochlear implant alone and also prevents auditory deprivation in the un-implanted ear. The aim of the study is to evaluate the benefits of bimodal stimulation in children in an Indian cochlear implant clinic. A group of 14 children who have been using cochlear implants served as subjects in this study. They were fitted with advanced digital hearing aids in their un-implanted ears to provide bimodal stimulation. Results revealed that bimodal stimulation did not bring greater change in speech scores in quiet surroundings but have shown a noticeable improvement in noisy ambience. Hence the present study suggests that bimodal stimulation would benefit children with cochlear implants especially in adverse listening conditions. PMID- 22319690 TI - Otitis media with effusion in children and its correlation with foreign body in the external auditory canal. AB - Otitis Media with Effusion (OME) is difined as the chronic accumulation of mucus within the middle ear and sometimes the mastoid air cell system. Significant hearing loss may go unnoticed and may result in improper development of speech and language. Foreign bodies in the external auditory canal of paediatric patients are commonly encountered in day-to-day practice. The purpose was to see if there is any relation between foreign bodies in ears and otitis media with effusion. A prospective study of consecutive cases was conducted between August 2005 and August 2007 at a teaching hospital. All children presenting with the history of a foreign body in the external auditory canal were included in this study. 50/74 that is 67.8% of the children in the study group had abnormal findings in the tympanogram whereas only 28/74 that is 37.8% children from the control group had abnormal findings in tympanogram. This study indicates that significant eustachian tube dysfunction to frank OME, causes irritation and/or earache in children which may compel them to put things into the ear. So children with an external auditory foreign body must be followed up in an ENT clinic. This may be an early opportunity to diagnose an underlying undetected OME and/or eustachian tube dysfunction in children, preventing the development of any complication from the undetected OME. PMID- 22319691 TI - Effective treatment of acute otitis externa: a comparison of steroid antibiotic versus 10% ichthammol glycerine pack. AB - To compare the efficacy of treatment between steroid-antibiotic and 10% Ichthammol glycerine packs (IG packs) in acute otitis externa. A prospective, randomized clinical trial between steroid-antibiotic and 10% IG pack which was performed in department of ENT-HNS, Kathmandu University Hospital, Dhulikhel from July 2009 to December 2009 on 82 patients. Pain was assessed by Numerical Rating Scale (NRS) and edema was assessed by dividing the external auditory canal in four quadrant giving score of 25% for each on the day of presentation and subsequent visits till tragal tenderness and edema subsided. Age group among studied patients ranged from 10 to 60 years, with mean of 23.5 years. Out of which 42 (51.2%) were females and 40 (48.8%) were males. Average number of visits in 10% IG pack group (n = 41) was 5.4 days (2-5 visits) while in steroid antibiotic group (n = 41) it was 3.5 days (2-5 visits). There was statistically significant decrease in the number of visits in steroid group (P < 0.05). Similarly, decrease in pain score in second visit was statistically significant (P = 0.02) in steroid-antibiotic group as compared to 10% IG pack, while the edema score in second visit while comparing steroid-antibiotic group with 10% IG pack was statistically not significant (P = 0.07), whereas it was statistically highly significant on fourth visit (P = 0.001). Since the control of pain and edema is more and hence the number of visits is significantly less in steroid antibiotic packing group, so it is worthwhile to use steroid-antibiotic pack for effective treatment of acute otitis externa. PMID- 22319692 TI - Inverted papilloma: a clinico-pathological dilemma with special reference to recurrence and malignant transformation. AB - To study the clinicopathological profile, recurrence and malignant potential of the inverted papilloma of nose and paranasal sinuses in relation to the definitive diagnosis and the management undertaken. A total number of 52 cases of histologically proven inverted papilloma managed in our department of otolaryngology over a 10-year period (May 1998-April 2008) were followed up (until October 2009) and the results were analyzed retrospectively to find out any incidence of recurrence of these tumours. A total of 52 inverted papilloma cases were managed with different surgical interventions. Male:female ratio was found to be 10:1. The mean follow up period was 74 months (range 16 months-11 years). Recurrence was observed in 20 (38%) cases. 23% had recurrence without any specific histological pattern, 12% had recurrence with focal dysplasia and 4% had recurrence with malignant transformation into squamous cell carcinoma (SCC). Post operative radiotherapy was given to 8% (four cases) with malignant transformation. The management of inverted papilloma depends on its size and extension. Recurrence can be minimized by an appropriate surgical planning. Careful endoscopic assessment is essential to detect early recurrence. Recurrent inverted papilloma should be treated more aggressively. Malignant transformation in inverted papilloma should be managed like any aggressive sino-nasal malignancy. PMID- 22319693 TI - The enlarged translabyrinthine and transapical extension type I approach for large vestibular schwannomas. AB - To evaluate the results obtained by performing the enlarged translabyrinthine and transapical extension type I approaches for removal of large vestibular schwannomas and those with anterior extensions. An academic tertiary referral centre at Mumbai, India. Retrospective case review. 35 patients of vestibular schwannomas having size greater than 3 cm in extrameatal diameter with extension anterior to the internal auditory canal who underwent the enlarged translabyrinthine or transapical extension type I approach and with a minimum follow up of 1 year are considered. Other subjects who underwent translabyrinthine approach but did not fulfill the above criteria were excluded. Tumor was removed completely in 34 subjects (97.1%). Anatomic interruption of facial nerve occured in 4 cases (11.4%); 3 subjects underwent end to end anastomosis and 1 subject required a cable graft, these were done during the primary procedure itself. At 1 year follow up 28 subjects (80%) had good facial function (Grade I and II, House Brackmann Grading). Postoperative cerebrospinal fluid leak was encountered in 1 subject (2.9%). 34 subjects (97.1%) had a normal albeit slow gait by the sixth post-operative day. Complete tumor removal with a very low morbidity in our series suggest that the enlarged translabyrinthine and transapical extension type I approach offers excellent control of the neurovascular structures in the cerebellopontine angle as also of the large vestibular schwannoma itself aiding complete removal. It also offers the advantage of management of the interrupted facial nerve at the primary procedure itself since the proximal and distal segments are in the operative field. PMID- 22319694 TI - Retrospective and prospective study of singapore swing method on healing of mastoid cavity. AB - Chronic suppurative otitis media with cholesteatoma is a common problem. The majority of ENT surgeons find the canal wall down operation to be the safest and simplest means of treating cholesteatoma. The 'Singapore Swing' is a method of promoting healing of mastoid cavity. In this study our main objective was to do Singapore Swing technique in larger number of cases, have long term follow-up and to compare its results with other mastoid operations in which obliteration has not been used. Patients of cholesteatoma were divided into case group and control group. The case group (26 patients) was operated by canal wall down procedure with Singapore Swing obliteration while the control group (62 patients) was operated by same method without any obliteration. Both retrospective and prospective studies were done. Time period of drying of mastoid cavity, numbers of visits to the hospital and hearing status were observed. Subjective satisfaction score of patient (0-10) and Surgeon's satisfaction score (fully satisfied, partially satisfied and not satisfied at all) were measured in both the groups. The time of drying of cavity was <2 months in 88.5% of cases, while 27.5% of controls. Mean time of drying of cavity was 46 days (11/2 months) in case group, while it was 89 days (3 months) in control group. Gain in air conduction was 11-30 dB in 33.3% cases and 15.7% of controls. 2 patients in control group had deterioration of 1-10 dB in air conduction. Subjective satisfaction score was 8-10 in 42.4% patients in case group, while 25% in control group. Surgeon was fully satisfied in 73% patients of case group and 45% patients of control group. The study suggested that Singapore Swing technique provides a dry, small and stable cavity with better hearing in less time. PMID- 22319695 TI - Suboccipital retrosigmoid surgical approach for internal auditory canal--a morphometric anatomical study on dry human temporal bones. AB - Suboccipital retrosigmoid craniotomy with removal of posterior wall of internal auditory canal is preferred by many surgeons operating on acoustic neuromas, as it is a simple and safe approach. To study the topographic landmarks of the posterior surface of the temporal bone. We studied the surgical anatomy of 224 dry adult human temporal bones, measured the various distances on posterior wall of petrous bone relevant for suboccipital surgical approach to internal auditory canal. The internal auditory canal (IAC) lies within 32-44 mm from posterior wall of sigmoid sulcus and within 3-8 mm from the superior border of petrous bone. The point corresponding to highest point of jugular bulb was found between 4 and 9 mm away from the inferior border of IAC. The maximum distance found between bony orifice of vestibular aqueduct and IAC was 14 mm and the minimum distance was 6 mm.The vertical diameter of IAC ranged between 3 and 7 mm. These parameters may help the surgeons for better exposure of internal auditory canal and for avoiding damage to vital surrounding structures. PMID- 22319696 TI - Qualitative and quantitative representation of taste disturbances: how we do it by pentagon chart. AB - Taste is a chemical sense responding to chemical stimuli. In our daily practice as ENT practitioners or Neurologists we do come across patients complaining of taste disturbances. Tests for taste have to be performed regularly in the clinical centres as well as in neurological labs as a part of complete work up for neurotology cases. Assessment of taste sensation can be easily done in a neurological clinic by chemogustometry as described by Claussen. The stimuli used are chemicals, representative substances for the four qualities of sweet, salty, sour and bitter, in graded solutions. These semi-quantitative results are plotted on a pentagon scheme devised by Claussen. The points of the best results for glucose, sodium chloride, citric acid, phenylthio-urea and quinine then are connected with a coloured line. That gives a linked graphic structure, which can be read by the physician at one glance. Different patterns are obtained for normal taste, taste-blindness for phenylthio-urea, ageusia, partial ageusias for glucose, or sodium chloride or citric acid or quinine or their combinations and parageusias. In this article we present different patterns of taste disturbances depicted on the pentagon chart highlighting the easy interpretation of chemogustometry. PMID- 22319697 TI - Incidence and presentation of fungal sinusitis in patient diagnosed with chronic rhinosinusitis. AB - Significant number of patients diagnosed with chronic rhino sinusitis often tend to have a final diagnosis of fungal sinusitis. We wanted to find out (a) The incidence of patients with fungal sinusitis in those patients who were initially diagnosed as chronic rhinosinusitis. (b) The presentation of fungal sinusitis patients who were initially diagnosed as CRS. Retrospective chart review of 242 patients diagnosed as CRS from May 2006 to April 2009. The various symptoms and signs of those diagnosed initially as CRS, who were then diagnosed as fungal sinusitis were tabulated. Radiological and serological investigations were then analyzed. The microbiology of various species that were cultured in those identified as fungal sinusitis were also presented. Out of 242 patients diagnosed with CRS, 67 patients had clinical and radiological evidence of fungal sinusitis but only 24 of these patients had fungal organisms identified. Majority of them were Aspergillus fumigatus. Clinical suspicion of fungal sinusitis should be made in those patients presenting with CRS with the following signs and symptoms of nasal obstruction, discharge and polyps. Most of those fungus were Aspergillus fumigatus and responded well to treatment. PMID- 22319698 TI - Role of radiofrequency cautery in laryngomalacia: a study in 12 patients. AB - Laryngomalacia is the most common condition causing inspiratory stridor at or shortly after birth accounting for approximately 60% of cases. Inspiratory stridor typically occurs after few days or week and is initially mild, but over a period of 6-9 months it gets more pronounced. Spontaneous improvement usually occurs over a period of 18 months to 2 years. Although majority of cases of laryngomalacia have benign course without any long-term sequel. Typically symptoms are worse during sleep and supine position while the same improves in prone position. There are 12 cases in the present study with the average age of the baby was 4.74 months (142 days). Male to female ratio of 1:1. Those babies with life-threatening apnea, significant cyanotic (blue) spells, failure to thrive with feeding difficulty, significant chest wall and neck retractions with breathing and requires oxygen to breathe were included in the study. One patient presented with tracheostomy tube in place. Two babies were preterm. These preterm babies were initially kept on ventilator before the final diagnosis was made. The findings were different in all the cases. The common findings are cyclical collapse of supraglottic larynx with inspiration, short aryepiglottic folds, indrawing of cuneiform and corniculate cartilages forward over the laryngeal inlet resulting in prolapse during inspiration. The surgical procedures in laryngomalacia babies were combined according to the type of laryngomalacia. The procedures performed were supraglottoplasty (Unilateral/Bilateral), epiglottoplasty, aryepiglottoplasty, aryepiglottic fold division, epiglottopexy. The procedures were performed by radiofrequency cautery under general anesthesia. The average hospital stay in nine patients was less then 36 h and more then 7 days in remaining three patients. In tracheostomized patient second surgical procedure was done as after the first procedure failed to decannulate the child. The postoperative period was uneventful. The average follow up was 10 months. PMID- 22319699 TI - Management of juvenile nasopharyngeal angiofibroma: a five year retrospective study. AB - Juvenile nasopharyngeal angiofibroma is a pathologically benign yet locally aggressive and destructive vascular lesion of head and neck region typically affecting adolescent boys. The present article is a retrospective study of surgically treated patients of juvenile nasopharyngeal angiofibroma over a period of 5 years. The study discusses about most common presenting complaints, correlation of preoperative radiological and intraoperative staging and factors affecting recurrence of juvenile nasopharyngeal angiofibroma. PMID- 22319700 TI - Speech evoked auditory brainstem responses: a new tool to study brainstem encoding of speech sounds. AB - The neural encoding of speech sound begins in the auditory nerve and travels to the auditory brainstem. Non speech stimuli such as click or tone bursts stimulus are used to check the auditory neural integrity routinely. Recently Speech evoked Auditory Brainstem measures (ABR) are being used as a tool to study the brainstem processing of Speech sounds. The aim of the study was to study the Speech evoked ABR to a consonant vowel (CV) stimulus. 30 subjects with normal hearing participated for the study. Speech evoked ABR were measured to a CV stimulus in all the participants. The speech stimulus used was a 40 ms synthesized/da/sound. The consonant and vowel portion was analysed separately. Speech evoked ABR was present in all the normal hearing subjects. The consonant portion of the stimulus elicited peak V in response waveform. Response to the vowel portion elicited a frequency following response (FFR). The FFR further showed a coding of the fundamental frequency (F0) and the first formant frequency (F1). The results of the present study throw light on the processing of speech in brainstem. The understanding of speech evoked ABR has other applications both in research as well as in clinical purposes. Such understanding is specially important if one is interested in studying the central auditory system function. PMID- 22319701 TI - Comparative evaluation of middle meatus antrostomy with or without partial middle turbinectomy. AB - A considerable controversy surrounds the advisability and efficacy of middle turbinate resection in endoscopic sinus surgery. Some are in favor of middle turbinate preservation considering it to be important anatomic and physiological structure and others advocate middle turbinate resection as it improves nasal air flow and decreases synechiae formation. So a study was undertaken to evaluate the efficacy of middle turbinate resection in patients of chronic sinusitis undergoing Functional Endoscopic Sinus Surgery (FESS). 40 patients of chronic sinusitis were selected and divided into 2 groups, group I undergoing FESS with middle turbinate preservation and group II undergoing FESS along with middle turbinate resection. Final results were recorded 6 months after the operative procedure. 50% patients had relief in nasal obstruction in group I as compared to 88% in group II. Postoperative synechiae formation was seen in five patients in group I and in one patient in group II. PMID- 22319702 TI - Unilateral maxillary swelling: a retrospective study. AB - Unilateral maxillary swelling is a rare condition, however we being in tertiary care centre did see a large number of these cases. All patients presenting with unilateral maxillary seen during the last 3 years were included in this retrospective study and evaluated concerning histories, diagnostic and therapeutic approaches and achieved outcomes. A total of 31 patients were seen during this period. 27 of these were benign lesions and were subdivided as follows: odontogenic cystic lesions (11/27), fibro-osseous lesions (8/27), secondary to extensive allergic fungal sinusitis (5/27) and mucocele (2/27). The remaining five were malignant lesions, two each were squamous cell cancer and adenocarcinoma of the maxillary sinus, and one was rhabdomyosacroma. All patients received treatment with due merit of the underlying etiology. Understanding and recognizing key diagnostic features helps in appropriate management and reducing morbidity. PMID- 22319703 TI - Tracheo oesophageal puncture voice: an Indian perspective. AB - Author presents in this study 160 patients who underwent tracheoesophageal puncture (TEP) for voice rehabilitation after laryngectomy. This study represents authors experience in Indian perspective with regards to technique, timing of surgery, i.e., primary or secondary, effect of socioeconomic condition of the patients. Author also narrated complications secondary to the TEP voice and prosthesis, during long follow-up of 15 years. The primary and secondary TEP were compared in patients having good socio-economical status with that of relatively poor status patients. As compared to the western literature, this Indian study showed significant differences in success rate of achieving good TEP voice production and also continuing use of TEP voice. Author observed that despite, entirely different socio economic condition and lack of proper follow-up, the secondary TEP done after complete evaluation of the patient yields much better sustained results for successful voice acquisition and continuation of the use of acquired voice. Author has described in details about the surgical procedures for secondary TEP; the prosthesis, care of prosthesis, problems due to TEP and prosthesis and the ways to rectify these problems. PMID- 22319704 TI - Comparative Study of FNAC and Excisional Biopsy in Thyroid Swelling. AB - To study the FNAC and histopathological pattern of thyroid swelling, prevalence of thyroid malignancy, mode of treatment and associated surgical complications. A total of 100 patients of thyroid swelling were evaluated by FNAC preoperatively and histopathologically after surgery. Reports of FNAC and histopathology were similar in 73% patients while dissimilar in 27%. Among benign tumors diffuse colloid goiter was the most common presentation. Thyroid disease is endemic and colloid goiter is the most common presentation. FNAC is useful in preoperative planning but final diagnosis should be based upon histopathology. PMID- 22319705 TI - Role of microsatellites instability in carcinogenesis of postcricoid carcinoma on top of plummer-vinson syndrome. AB - To develop a molecular pattern that might help in understanding carcinogenesis of postcricoid carcinoma (PCC) on top of Plummer-Vinson syndrome (PVS) in a prospective controlled study. Twenty-four patients with PVS were diagnosed and followed up over a 4 year period, during which eight of them showed malignant change to PCC. Twenty volunteers free of neoplastic diseases were included as a control group. In the two groups, DNA extraction from mononuclear peripheral blood cells, and analysis of loss of heterozygosity (LOH) and microsatellite instability (MSI) using six paired simple tandem repeats (STRs) primers were done. The molecular weight of each STRs locus was scored and statistical correlations were performed. LOH occurred in 55.6 and 72.9% of PVS and PCC cases compared to 25% of control group. At loci D17S695, D9S753 and D9S171, LOH occurred in 54.2, 66.7, and 70.8% of PVS cases; and in 62.5% of PCC cases for each locus compared to 15, 25 and 45% of control cases. D3S1286 and CFS1-R displayed the highest frequency of LOH in PCC (100% for each) while recorded in 58.3 and 33.3% in PVS compared to 30 and 0% in control cases. Certain genetic events tend to occur as early and late events in malignant change of PVS to PCC. Detection of these events may help in understanding carcinogenesis and in early detection of malignancy. CFS1-R is the most informative marker of tumor progression. PMID- 22319706 TI - Ossicular chain status in chronic suppurative otitis media in adults. AB - This study was conducted to find out the status of the ossicles in cases of chronic suppurative otitis media (CSOM). One hundred and fifty cases of CSOM, who underwent surgery, were included and their intra-operative ossicular chain findings noted. Ossicular erosion was found to be much more common in unsafe CSOM than in safe CSOM. Malleus was found to be the most resistant ossicle to erosion whereas incus was found to be the most susceptible. PMID- 22319707 TI - Endoscopic adenoidectomy with microdebrider. AB - To describe endoscopic power assisted adenoidectomy and review the experience with the procedure demonstrating its safety and efficacy. Prospective study of 44 patients aged between 7 to 15 years undergoing power assisted adenoidectomy between Jan 2004 and July 2006. Tertiary care private teaching hospital. Forty four consecutive children with adenoid hypertrophy undergoing power assisted adenoidectomy. Therapeutic endoscopic adenoidectomy using microdebrider. Operative time, blood loss, complications, completeness and depth of removal, surgeon's satisfaction and recovery period. The average operative time was 12 min (range: 8-16 min) and average blood loss was 30 ml (range: 24-42 ml). Complete resection was possible under vision with few complications. The surgeon satisfaction was high and post-operative recovery good. Power assisted adenoidectomy is quick, precise and safe. There is good visualization during resection thus improving precision and ensuring complete removal of adenoid tissue. PMID- 22319708 TI - Endoscopic Approach to Fisch Stage II to III-b Juvenile Nasopharyngeal Angiofibroma. AB - Juvenile nasopharyngeal angiofibroma (JNA) are locally growing highly vascular tumours treated primarily by surgical excision (open approach as wide as a mid facial degloving or endoscopic approach). All our patients underwent exclusive endoscopic tumour excision after a pre-operative embolisation. The tumours were completely resected with acceptable blood loss and no recurrences or residual masses were seen. Post-operative morbidity was minimal without external scar marks. To conclude endoscopic excision is a very effective method to resect JNA even for extensive tumours. PMID- 22319709 TI - Topical beclomethasone in the therapy of smelling disorders-a new application technique. AB - Systemic corticosteroid is the first-line-treatment for olfactory dysfunction of sinonasal origin but is afflicted with many side-effects. Topic corticosteroid does not reach the same efficacy but has a remarkable safety profile. In this trial we investigated the efficacy of topic therapy with beclomethasone (BDP) spray. The drug was applied precisely to the olfactory cleft by a special spraying top-part. In addition we determined extinction and volume of a gelaspon sponge placed in the olfactory cleft to show the difference of the topical spray application. 18 patients with anosmia or hyposmia of different genesis and duration applied BDP-spray twice daily for four weeks. The olfactory function was determined using the TDI score ('Sniffin'-Sticks test battery'). Factors correlated with therapy efficacy were assessed. The median TDI score increased from 13.5 (0-25) at the beginning to 18.5 (1-26) after therapy of four weeks (P = 0.005). The extinction and volume in the moistened sponge was more than two times greater with the top-part than without. The direct application of BDP-spray to the olfactory cleft attained superior therapeutic effects than a usual applied mometasone spray, but did not perform as good as systemic corticosteroid treatment. PMID- 22319710 TI - The role of sensation in subjective and objective evaluation of nasal patency. AB - To assess if sensation of nasal mucosa affect the subjective sensation of nasal patency. This is a case control study with 50 patients, using 2% lignocaine as the active drug and normal saline as the placebo (2 groups of 25 patients each). Each subject had 2 ml of solution sprayed into the test nose. These subjects had no prior nasal symptoms, allergy or surgery. They were evaluated subjectively using Likert scale and objectively by acoustic rhinometry before and after lignocaine or normal saline. The patients in both normal saline and lignocaine groups demonstrated no significant change based upon Likert scale. The study also demonstrated the mean cross sectional area 1 (CSA1), mean cross sectional area 2 (CSA2), with mean Volume 1 and mean Volume 2, these results did not vary significantly in both groups with Acoustic Rhinometry. The analysis thus shows that the use of topical anesthetic spray on nasal mucosa produces no objective effect on nasal resistance or subjective sensation of altered nasal patency. Thus the study concludes that, tactile sensation of nasal mucosa does not play a role in the sensation of nasal obstruction. PMID- 22319711 TI - Ligation versus bipolar diathermy for hemostasis in tonsillectomy: a comparative study. AB - Tonsillectomy despite being less performed nowadays still is a very common surgery performed by ENT surgeons. The use of various modalities like bipolar diathermy, laser, cryosurgery, radiofrequency and ionic coblation for hemostasis in tonsillectomy remains controversial so far. A thorough scan of literature comparing the ligation with diathermy has been presented. In this prospective study, we analysed 50 patients undergoing tonsillectomy by dissection method. Right sided tonsillectomies act as study group (bipolar diathermy used) and left sided tonsillectomies as the control group (ligation for hemostasis used). The aim of our study is to compare the amount of blood loss, number of ligatures applied, average time taken and incidence of postoperative haemorrhage following the use of ligation and bipolar diathermy. The study found that diathermy hemostatic technique is associated with a quicker procedure, less intraoperative blood loss, comparable postoperative pain. PMID- 22319712 TI - A randomized control trial to verify the efficacy of pre-operative intra venous tranexamic Acid in the control of tonsillectomy bleeding. AB - Tonsillectomy is an age old surgery which is still very commonly done. Bleeding related to surgery is the major problem. This study is done to verify by randomized control trial the efficacy of preoperative intravenous tranexamic acid in the control of tonsillectomy bleeding. Hundred cases undergoing tonsillectomy were randomized into two groups, one of which received pre-operatively intra venous tranexamic acid, 10 mg kg(-1). The other group patients were given a placebo. Amount of bleeding was assessed in each case. The study group had statistically highly significant reduction in bleeding. There were no side effects of the drug. This finding is similar to that in other studies for tonsillectomy, other surgeries and other hemorrhagic conditions. Tranexamic acid in the dose of 10 mg kg(-1) given intra venous pre-operatively is effective in the control of tonsillectomy bleeding. PMID- 22319713 TI - Electroglottographic parameterization of the effects of gender, vowel and phonatory registers on vocal fold vibratory patterns: an Indian perspective. AB - In-depth study on laryngeal biomechanics and vocal fold vibratory patterns reveal that a single vibratory cycle can be divided into two major phases, the closed and open phase, which is subdivided into opening and closing phases. Studies reveal that the relative time course of abduction and adduction, which in turn is dependent on the relative relaxing and tensing of the vocal fold cover and body, to be the determining factor in production of a particular vocal register like the modal (or chest), falsetto, glottal fry registers. Studies further point out Electroglottography to be particularly suitable for the study of vocal vibratory patterns during register changes. However, to date, there has been limited study on quantitative parameterization of EGG wave form in vocal fry register. Moreover, contradictory findings abound in literature regarding effects of gender and vowel types on vocal vibratory patterns, especially during phonation at different registers. The present study endeavors to find out the effects of vowel and gender differences on the vocal fold vibratory patterns in different registers and how these would be reflected in standard EGG parameters of Contact Quotient (CQ) and Contact Index (CI), taking into consideration the Indian sociolinguistic context. Electroglottographic recordings of 10 young adults (5 males and 5 females) were taken while the subjects phonated the three vowels /a/,/i/,/u/ each in two vocal registers, modal and vocal fry. Obtained raw EGG were further normalized using the Derived EGG algorithm and theCQ and CI values were derived. Obtained data were subject to statistical analysis using the 3-way ANOVA with gender, vowel and vocal register as the three variables. Post-hoc Dunnett C multiple comparison analysis were also performed. Results reveal that CQ values are significantly higher in vocal fry than modal phonation for both males and females, indicating a relatively hyperconstricted vocal system during vocal fry. The males have significantly greater CQ values than females both at modal and vocal fry phonations which indicate that the males are predisposed to greater vocal fold constriction. Females demonstrated no significant increase in CI values in vocal fry state; and in some cases actually decrease in the CI values which suggest an inherently distinct vocal fold physiological adjustment from that in males. No vowel effects were found in any conditions. Perturbation values (CQP and CIP) are significantly more in vocal fry register than in modal register, and the increase was more in case of females than males. The findings give strong evidence to certain hypotheses in literature regarding effects of vowel, gender and phonatory register on vocal fold vibratory patterns. PMID- 22319714 TI - Perceptual and acoustic analysis of voice in individuals with total thyroidectomy: pre-post surgery comparison [corrected]. AB - Total thyroidectomy (TT) is a surgical procedure which involves complete removal of the thyroid gland, usually done in massive goitre compressing the trachea and esophagus, hyperthyroidism and carcinoma of thyroid gland. Laryngeal nerve damage is one of the most feared complications after TT which can lead to permanent changes in voice. Recent research suggests the occurrence of voice changes without any visible laryngeal nerve damage. Present study attempts to compare the pre and post-operative voice characteristics in individuals with total thyroidectomy without any laryngeal nerve damage. A total of 27 subjects (21 females and 6 males) who underwent total thyroidectomy participated in the study. Their recorded phonation of vowel/a/was subjected to two types of analyses viz. Perceptual analysis (using CAPE-V rating scale) and Acoustic analysis (using Multi Dimensional Voice Profile). Results of perceptual analysis indicated slight decrease in overall severity, roughness and breathiness and a slight increase in strainness, in only males. Acoustic analysis findings supported perceptual results with minimal changes in most of the parameters. The results suggest that after total thyroidectomy, in the absence of visible laryngeal nerve damage, functional changes in voice are minimal and temporary in nature. This study provides an insight to Otolaryngologists and Speech Language Pathologists about the voice characteristics in individuals with thyroidectomy, enabling them to formulate appropriate therapy protocol for this population. It further attempts to sensitize surgeons and physicians on the need for referral of this population to Speech Language Pathologist in the event of dysphonia. PMID- 22319715 TI - Improving Results in Endoscopic DCR. AB - The aim of presenting this article is to highlight the factors causing failure in endoscopic dacryocystorhinostomy (DCR). Understanding these factors will lead to an enhancement in the success rate of endoscopic DCR. Out of 600 cases done in a period of 10 years (from 1998 to 2008), 60 were revision cases. 60 patients referred over a period of 10 years, were selected. The aim was to study the factors causing failure in each case. The cases included were revised in a period of 10 years from 1998 to 2008. These were the cases that were unsuccessful for one or the other reason. The author presents a series of failed DCR cases referred over a period of 10 years. Patients had undergone primary surgery elsewhere and were referred due to the persistence of symptoms. Assessment of all the cases was done with the examination of Eyes and lids for any obvious deformity, watering or purulent discharge in the medial canthal area. ROPLAS test was done as a spot diagnosis for NLD block. This was followed by probing and syringing in the outdoor. All the cases were revised and the likely causes leading to failure of the first surgery were analyzed. It was found that the improper selection of cases accounted for 3.3% of total failed cases; Low rhinostomy accounted for 28.3% cases, inadequate sac opening for 38.3% cases, Pre existing canaliculitis for 1.6% of cases, contracture at the rhinostomy site in 10% cases. Laser burn canalicular scarring for 3.3% of total cases and laxity of the lids and atonic sac was responsible for failure in 3.3% cases. Most of the above factors are secondary to the false localization of the sac, inadequate removal of the sac wall, too much of mucosal removal leading to synaechia formation at the surgical site and inability to detect any additional block with NLD (Nasolacrimal duct) block. PMID- 22319716 TI - Peripheral auditory assessment in minor head injury: a prospective study in tertiary hospital. AB - Hearing loss is a common problem encountered in ENT practice. Hearing loss following head injury is a major medical problem in both adults and children, which may go unnoticed when it does not affect speech frequencies. Sensorineural hearing loss at high frequencies is a common finding in minor head injury. Patients with history suggestive of mild head injury (MHI) according to Glasgow coma scale score were evaluated. The most common cause of MHI was road traffic accidents involving two wheeler riders without helmets. Higher the frequencies affected, and severe the hearing loss, poorer was the prognosis. Distortion product oto-acoustic emissions assessment at 3000 and 4000 Hz were found to be significant and has a higher predictive value in assessing outer hair cell damage. PMID- 22319717 TI - Endoscopic sinus surgery in chronic rhinosinusitis and nasal polyposis: a comparative study. AB - Nasal polyposis are common presentations in patients of chronic rhinosinusitis and are considered to be associated with more severe forms of disease with poor treatment outcome. The presentation and treatment outcome after endoscopic sinus surgery in patients of chronic rhinosinusitis and nasal polyposis have been analysed in this study. A prospective analysis of 90 patients of chronic rhinosinusitis who were classified into two groups depending on presence and absence of nasal polyps was performed in the study. The two groups were evaluated using subjective (patient complaints) and objective (computed tomography scan and endoscopy scores) criteria. Preoperative data were compared with data obtained 12 months post endoscopic sinus surgery. The study included 38 patients of chronic rhinosinusitis and 52 patients of nasal polyps. The patients of nasal polyp group presented with increased severity of symptoms of nasal blockage, nasal discharge and reduced sense of smell as compared to the chronic rhinosinusitis group who had significantly higher presentation of headache and facial pain. The preoperative CT scan revealed significantly higher bilateral disease with increased involvement of multiple sinuses in nasal polyp group. Post endoscopic sinus surgery both the groups showed significant improvement in their symptoms with the nasal polyp group demonstrating reduction in improvement on 1 year follow up. In our study we have found the patients with chronic rhinosinusitis and nasal polyp have varied severity of symptoms with the nasal polyp group having higher nasal symptoms and increased severity as compared to chronic rhinosinusitis group. Though the universal rationale of management by adequate drainage and ventilation of sinus is similar in both groups, there is a reduction in both objective and subjective scores during 1 year follow up in the nasal polyp group. PMID- 22319718 TI - Comparison of Histopathological and CT Findings in Experimental Rabbit Sinusitis. AB - The aim of this study was to investigate and compare histopathological and computerized tomographic (CT) findings of experimental acute sinusitis in an animal model. The noses of five healthy rabbits were inoculated with a gelatin sponge impregnated with a solution containing Staphylococcus aureus, and one healthy rabbit acted as the control. The animals were sacrificed on the tenth day, following the acquisition of paranasal CT scans. Specimens were obtained from the lateral nasal walls, and the ethmoid and maxillary sinuses of the animals for histopathological examination. Histopathological and CT findings were compared. Various degrees of epithelial disorganization, foci of ruptured epithelial cells, and inflammatory cell infiltration in the lamina propria were seen in the histopathological examinations of the five study rabbits, and mucosal thickening and soft tissue density were noted in their CTs. There was no correlation between the histopathological and CT findings. It was shown that CT did not reflect the acute changes in the sinus mucosa. Patients with chronic sinusitis must be evaluated for a chronic process. Computerized tomographic scans should not be obtained in acute sinusitis cases. In this way, both unnecessary radiation exposure and economic waste can be avoided. PMID- 22319719 TI - "Ancient" schwannoma of hypopharynx: a case report with review of literature. AB - The "ancient" variant of schwannomas is a rare subtype of a benign encapsulated neoplasm of nerve sheath. A review of current literature has revealed several reported sites but not in the hypopharynx. Here we report such a hypopharyngeal tumour arising in a 32 year old man, paying particular attention to the potential diagnostic difficulties. PMID- 22319720 TI - Paragangliomas of the Head & Neck: the KMC experience. AB - To determine the clinical features, investigations, intra-operative findings, surgical approaches used and the results of the treatment for paragangliomas of the head and neck. Retrospective study of 14 cases of paragangliomas in head and neck seen over a period of 10 years including five carotid body tumors, seven glomus jugulares and two glomus tympanicums. HRCT scans and bilateral carotid angiography were done in all cases of glomus jugulare. Pre-operative embolization was done in most cases. The trans-cervical approach was used for all cases of carotid body. In three cases of Type B jugulare tumors, a post-aural tympanotomy was used. A Fisch Type A approach was done for three cases of Type D jugulare tumors. Postaural tympanotomy approach was used for both patients with glomus tympanicum. In one case of extratympanic glomus jugulare tumor with hypoglossal palsy, a neck exploration was done to isolate and excise the tumor. Five patients with carotid body tumors presented as unilateral, painless, pulsatile swelling in the upper neck. Intra-operatively, three of the tumors were classified into Shamlin's Grade II and one each into Grade III and Grade I. A carotid blow-out occurred in one of the patients with Grade II disease, which was managed. ECA resection had to be done in one case. Seven patients were diagnosed to have glomus jugulare and two with glomus tympanicum. Six glomus jugulare tumors presented with hearing loss, ear discharge and obvious swelling. Glomus tympanicums presented with hearing loss but no bleeding from the ear. On examination, tumors presented with an aural polyp with no VII nerve deficits. Both tympanicums were classified as Fisch Type A, three of the jugulares classified as Type B, two as Type D2 and one as Type D1. Tumors were found to be supplied predominantly by the ascending pharyngeal artery. In three cases of Type B jugulare tumors, a post-aural tympanotomy was used. A Fisch Type A approach was done for three cases of Type D jugulare. The transcanal approach was used for both patients with glomus tympanicum. Paragangliomas are uncommon tumors that need accurate diagnosis and skilled operative techniques. Though the surgical approaches may appear complicated, the removal provides good cure rates with minimal morbidity and recurrence. Lateral skull base approaches should be the armamentarium of every head and neck surgeon. PMID- 22319721 TI - Evaluation of audio-rhinological changes during pregnancy. AB - A number of physiological changes occur during pregnancy and amongst them, audiological and nasal changes are quite significant. These are mainly due to the changing levels of sex hormones and return to normal once the pregnancy is over. This study was conducted to document these changes. Forty (pregnant 40 and non pregnant 40) consenting subjects in age group of 20-35 years were assigned to test and control groups. They underwent complete ENT and Obstetric examination. In test group Pure Tone Audiometry was performed in all trimesters of pregnancy and within 3 months of delivery. The subjects in the control group underwent pure tone audiometry only once. The nasal patency was measured by Gertner's plate method. Results from each trimester and postpartum period were compared. A highly significant difference in pure tone thresholds was observed at frequencies ranging from 125 to 1000 Hz (P < 0.001). However frequencies higher than 1000 Hz demonstrated no significant correlation. Nasal patency as measured by mean area of vapour condensation in all trimesters and control groups was highly significant (P < 0.001). The results of this study confirm that these changes occur in the first trimester and gradually improve during the subsequent trimesters returning to normal in post partum period. However number of pregnancies bear no relationship with these changes. PMID- 22319722 TI - Selecting the best approach to the frontal sinus. AB - The Messerklinger technique is an endoscopic approach to sinus surgery designed to be minimally invasive and preserve mucosa and hence physiological function. More recently there have been advocates for more radical endoscopic approaches to the frontal sinus such as the Modified Lothrop. This review discusses different approaches to frontal sinus surgery including any advantages and disadvantages to each approach. After examining the evidence from the literature, meticulously performed endoscopic frontal sinusotomy with or without computer guidance appears to be the most effective minimally invasive procedure for treating chronic frontal sinusitis secondary to outflow tract obstruction. Properly performed, it is almost always effective in dealing with even the most diseased frontal sinus. It offers clear advantages in reducing complications and recurrence rates in frontal sinus disease, even for revision cases. PMID- 22319723 TI - Laryngeal amyloidosis: a case report. AB - We report a case of Amyloidosis of larynx in a 60-year-old adult who reported to us with hoarseness of voice of 3 years long duration and no other symptoms. Patient was treated successfully with endoscopic curettage of the mass with no inadvertent ill effects. PMID- 22319724 TI - Giant mucocoele of the maxillary antrum: a case report. AB - Maxillary antral mucocoeles have an incidence of only 3-10%. Mucocoeles are more commonly seen in the frontoethmoidal region. We present one such rare case of a 52-year-old lady who came to us with complaints of pain and swelling of the left cheek of 4 months duration. Clinical examination and investigation revealed a giant maxillary sinus mucocoele which was duly treated surgically. We discuss its classical presentation and management since such large mucocoeles are not often seen in the maxillary sinus. PMID- 22319725 TI - Cystic hygroma with extensive tongue involvement. AB - Cystic Hygroma is a congenital lymphangiomatous tumour. It commonly involves the neck but is rarely associated with lymphangioma of the tongue. Presenting here a rare case having extensive tongue involvement giving a terrifying look and severe anaemia but without respiratory distress. Herewith submitting a case report with a brief review of literature and various problems faced while managing the same. PMID- 22319726 TI - A case report of cervical thymic cyst and review of literature. AB - We are reporting a case of 10-year-old female child with an asymptomatic left sided cystic neck mass who underwent surgical excision. She was diagnosed as having a cervical thymic cyst based on histopathologic findings. The review of available literature on thymic cyst has shown that cervical thymic cyst is a rare occurrence, but should always be thought of in the differential diagnosis of cystic masses in the neck especially presenting in children. PMID- 22319727 TI - An unusual presentation of impacted foreign-body in the adult larynx. AB - Foreign-bodies in the aero-digestive tract are a frequent occurrence in ENT practice. The diagnosis and management are based on clinico-radiological findings. We report a case of a 50 paise coin impacted in the adult larynx where the patient came to us 3 days later with the symptom of change of voice and pain in the throat but, surprisingly no dyspnoea or stridor. PMID- 22319728 TI - Monopolar suction diathermy adenoidectomy: technical note. AB - Monopolar suction diathermy allows controlled resection of the adenoids in a near bloodless field. In this article the author describes some technical points to make the procedure safe. PMID- 22319729 TI - Abdominal compartment syndrome caused by a bulimic attack in a bulimia nervosa patient. AB - We present a rare case of abdominal compartment syndrome due to a bulimic attack in a 19-year-old female patient with bulimia nervosa. She was admitted to our emergency room with complaints of progressive abdominal pain following bulimia. Computed tomography showed dilated stomach with food and air pressed other visceral organs and major abdominal vessels. Decompression using nasogastric tube or gastric lavage tube failed. At laparotomy, we performed gastrotomy and decompression was performed. After decompression, she fell into hypovolemic shock due to bleeding in the intra-gastric and peritoneal cavity. Twelve hours after the operation, the patient died due to refractory hypovolemic shock from uncontrolled bleeding following decompression of abdominal compartment. It should keep in mind that binge-eating habits in patients with bulimic nervosa could cause abdominal compartment syndrome due to gastric distension and this may be a potentially fatal condition. PMID- 22319730 TI - Primary papillary carcinoma originated from a branchial cleft cyst. AB - Although branchial cleft cysts are common, papillary carcinomas arising from them are rare. Here we report a 41-year-old woman with papillary carcinoma originating from a right lateral branchial cleft cyst without any evidence of a papillary carcinoma in the thyroid gland. The patient underwent right lateral neck dissection followed by total thyroidectomy. We then confirmed papillary carcinoma arising from the branchial cleft cyst through microscopic and immunohistochemical staining with thyroglobulin (TG), thyroid-associated transcription factor-1 (TTF 1) and p63. It is the 10th case worldwide describing papillary carcinoma in a branchial cleft cyst with a review of the literature on the features of the disease and discussion of the role of immunohistochemical staining with TG, TTF 1 and p63. In conclusion, it should be emphasized that the surgeon must be cautioned of the possibility of primary papillary carcinoma in the branchial cleft cyst. PMID- 22319731 TI - Difficult evaluation of thyroid cancer due to cervical paraffin injection. AB - Paraffinoma is a well known complication of previous paraffin injection into the subcutaneous layer that presents as various conditions including firm mass formation, edema, induration, ulceration, and skin necrosis. Paraffinoma can mimic neoplasm on physical examination and imaging studies and may complicate ultrasonographic diagnoses due to typical posterior shadowing and high echogenicity. When paraffinomas involve around the thyroid gland, the diagnosis of thyroid tumors is very difficult. We present a case of thyroid cancer, the evaluation of which was complicated by the presence of cervical paraffinoma. PMID- 22319732 TI - Robot-assisted posterior retroperitoneoscopic adrenalectomy: single port access. AB - Laparoscopic adrenalectomy has become a gold standard in adrenal gland surgery. More recently, some minimally invasive trials have been conducted on single access surgery on the adrenal gland. In this study, we introduce our first experiences of robot-assisted posterior retroperitoneoscopic adrenalectomy using single-port access and the da Vinci system. PMID- 22319733 TI - Recurring gastrointestinal stromal tumor with splenic metastasis. AB - Malignant gastrointestinal stromal tumors (GISTs) are rare non-epithelial, mesenchymal neoplasms of the gastrointestinal tract that metastasize or recur in 30% of patients who undergo surgical resection with curative intent. A 59-year old man visited our hospital for an examination of a palpable mass in the left abdomen. Fourteen months prior to his visit, the patient underwent gastric wedge resection to remove a GIST of the gastric cardia. At the time of surgery, no evidence of metastatic disease was observed and the pathological interpretation was a high-risk GIST. A follow-up computed tomography scan of the abdomen revealed a partially necrotic solid mass (9.8 * 7.6 cm) and enhancing mass in the spleen (2.3 cm). On exploration, multiple masses were found in the liver, greater omentum, and mesentery. Here, we report a case of recurring GIST of the stomach that metastasized to the spleen. To the best of our knowledge, few reports of metastasis to the spleen exist. PMID- 22319734 TI - A case of anaphylactic shock attributed to latex allergy during gastric cancer surgery. AB - Latex allergy is a known cause of allergic contact dermatitis. It produces mild symptoms, including skin rash and itching, which usually subside in a few days. However, latex allergy can also induce anaphylaxis, a severe type I hypersensitivity reaction that can cause urticaria, angioedema, hypotension, tachycardia, and bronchospasm. We report a case of anaphylactic shock during gastric cancer surgery in a patient with no previous allergic history. Surgery was suspended when hypotension, tachycardia, and wheezing developed. A thorough workup revealed that the patient had a latex allergy. The patient subsequently underwent curative gastrectomy performed with latex-free procedures. PMID- 22319735 TI - Laparoscopy-assisted distal gastrectomy for early gastric cancer and laparoscopic cholecystectomy for gallstone with situs inversus totalis: a case report. AB - We report our case of laparoscopy-assisted distal gastrectomy with D1 + beta lymph node dissection for a patient with early gastric cancer and laparoscopic cholecystectomy for gallstone with situs inversus totalis. A superficial elevated lesion was found on the lesser curvature of the antrum. The preoperative diagnosis was cStage IA (cT1, cN0, cH0, cP0, cM0). A 1 cm-sized gallstone was found in the fundus through upper abdominal ultrasound. A laparoscopy-assisted distal gastrectomy with standard D2 lymph node dissection for early gastric cancer and laparoscopic cholecystectomy was successfully performed by not shifting the monitor to the left and right and not changing operator's position without additional blood loss and time. The number of retrieved lymph nodes was 36. We have not found any abnormal course of blood vessels except for the right/left inversion. Billroth I reconstruction was performed through end-to-side anastomosis. Based on a histopathological examination, a 1.5 * 1.5 cm, submucosal (sm3), moderately differentiated adenocarcinoma (pT1, pN0, sH0, sP0, sM0, stage IA) was diagnosed. The postoperative course was favorable and the patient was discharged on postoperative day 7. PMID- 22319736 TI - Edematous and painful external hemorrhoids following intersphincteric resection for low rectal cancer. AB - Intersphincteric resection (ISR) is the ultimate sphincter saving procedure for low rectal cancer. Hemorrhoids are a common benign condition. We present and discuss a case of ISR which developed painful edematous hemorrhoids after ISR. A 62-year-old female with low rectal cancer received neoadjuvant chemoradiotherapy with successful down staging of tumor before undergoing robot assisted ISR with coloanal hand-sewn anastomosis. She had pre-existing external hemorrhoids which were not excised. She developed painful and edematous external hemorrhoids 4 days after surgery. These were treated conservatively before discharge. Many colorectal surgeons performing ISR have experienced similar situations in their patients, but none have reported on this phenomenon. We discuss the possible factors that may contribute to this situation. A possible solution is prophylactic excision of the hemorrhoids during coloanal anastomosis. Painful hemorrhoids may occur after ISR and if managed conservatively, the outcome is skin tags. PMID- 22319737 TI - Metastasis to the breast from colonic adenocarcinoma. AB - A 63-year-old woman was referred to a breast surgeon with a breast mass discovered incidentally during follow-up study after colon cancer surgery. Invasive adenocarcinoma was revealed on core needle biopsy. Wide excision of the breast including the tumor was performed. On standard histological examination the tumor showed features of moderately differentiated adenocarcinoma. The immunohistochemistry study revealed positive results for cytokeratin (CK)20 and CDX2, but negative for CK7. These are typical characteristics for colon cancer. Considering her history of subtotal colectomy for sigmoid colon cancer, it is presumable that the mass in the breast was of colonic origin, and it was an extremely rare case of metastasis to the breast from primary colorectal neoplasm. Although the instance is rare, clinicians should keep the possibility of breast metastasis from colorectal cancer in mind for early and correct diagnosis. PMID- 22319738 TI - Torsion of a mucocele of the vermiform appendix: a case report and review of the literature. AB - Torsion of a mucocele of the vermiform appendix is an extremely rare condition and also a rare cause of an acute abdomen with a clinical presentation that is indistinguishable from acute appendicitis, and thus, the condition is diagnosed during operation. Here, the authors describe the case of a 78-year-old female, who presented with intermittent abdominal pain. The appendix had a pelvic position and the torsion was counterclockwise. In addition, the torsion was associated with mucocele of the appendix, which was considered a secondary factor of torsion. Appendectomy and drainage were performed. PMID- 22319739 TI - Mucinous cystadenoma of the liver with ovarian-like stroma: the need for complete resection. AB - Cystadenoma of the liver is a rare neoplasm. Although many cystadenomas are asymptomatic, symptoms can include abdominal pain, postprandial epigastric discomfort, and nausea. Dramatic changes in hepatic imaging techniques have been helpful for diagnosing cystic lesions of the liver, such as simple cyst, hydatid cyst, cystadenoma, cystadenocarcinoma, and metastatic neuroendocrine tumors. However, it remains difficult to differentiate cystadenoma from cystadenocarcinoma for multiseptated cystic hepatic lesions with papillary projection on computed tomography (CT) and magnetic resonance imaging (MRI). Here we report the case of a 47-year-old woman with several months of postprandial discomfort and abdominal fullness. CT and MRI revealed multiseptated cystic lesions with papillary excrescences. A left hemihepatectomy was performed. Histology showed a benign mucinous cystic tumor with ovarian-like stroma. PMID- 22319740 TI - Solid pseudopapillary tumor with hepatic metastasis. AB - Solid pseudopapillary tumor of the pancreas is a rare tumor that affects young females with low malignant potential and good prognosis with more than 90% survival at 5 years. Metastasis is very rare. We report the case of a 74-year-old female who had pancreatic solid-pseudopapillary tumor and synchronous hepatic metastasis. PMID- 22319741 TI - Aggressive hilar inflammatory myofibroblastic tumor with hilar bile duct carcinoma in situ. AB - Inflammatory myofibroblastic tumor (IMT) of the biliary tree is extremely rare and is generally a benign condition, though malignant change is possible. Making a differential diagnosis between this lesion and other malignant conditions is very difficult on preoperative imaging studies. Hence, the final diagnosis of IMT may be made during or after operation depending on the pathologic examination. We treated a 63-year-old woman who received right hepatectomy with caudate lobectomy under the suspicion of hilar cholangiocarcinoma. Frozen biopsy during the operation showed carcinoma in situ and there were stromal cells in the bile duct's resection margins. The postoperative hospital course was uneventful except for minor bile leakage. At postoperative month 4, she developed jaundice, ascites and pleural effusion. Computed tomography images showed a mass-like lesion in the porta hepatis with portal vein thrombosis and a right chest wall mass. Excisional biopsy was done and the pathology report was malignant spindle cell tumor suggestive of an aggressive form of IMT. Her condition rapidly deteriorated regardless of the best supportive care and she expired at postoperative month 5. Further investigation is necessary to clarify the reasons for recurrence and infiltration of this disease. PMID- 22319742 TI - Simultaneous forequarter amputation and radical mastectomy for metastatic breast carcinoma in a male patient: a case report. AB - Although the majority of forequarter amputations are performed for high-grade bone and soft tissue sarcomas or extensive osteomyelitis of the upper extremity, this radical operation may also be indicated for the curative treatment of recurrent breast cancer and for the palliation of locally advanced breast cancer. We report a male patient with metastatic breast adenocarcinoma who underwent simultaneous mastectomy and forequarter amputation for the management of both his primary and metastatic disease. PMID- 22319743 TI - Chylous ascites caused by acute pancreatitis with portal vein thrombosis. AB - Chylous ascites is defined as the accumulation of chyle in the peritoneum due to obstruction or rupture of the peritoneal or retroperitoneal lymphatic glands. Chylous ascites that arises from acute pancreatitis with portal vein thrombosis is very rare. We report here on a case of chylous ascite that was caused by acute pancreatitis with portal vein thrombosis, in which the patient showed an impressive response to conservative therapy with total parenteral nutrition and octerotide. We also review the relevant literature about chylous ascites with particular reference to the management of this rare disease. PMID- 22319744 TI - Primary leiomyosarcoma of the pancreas. AB - Primary sarcomas of the pancreas are extremely rare, accounting for 0.1% of malignant pancreatic (non-islet) neoplasms. Pancreatic leiomyosarcoma is a highly aggressive malignancy that spreads in a similar manner to gastric leiomyosarcoma, i.e., by adjacent organ invasion, hematogenous spread, and lymph node metastasis. These tumors are large at the time of diagnosis and are usually found at an advanced stage. We report a case of a 70-year-old female with intermittent right upper quadrant abdominal discomfort. Radiological, histopathological, and immunohistochemical studies revealed the tumor to be a primary leiomyosarcoma of the pancreas. Herein, we describe a patient with a primary leiomyosarcoma of the pancreas who presented with clinical and radiological findings indicative of a mass in the pancreatic head. PMID- 22319745 TI - Laparoscopic transabdominal extraperitoneal mesh repair of lumbar hernia. AB - Lumbar hernias are rare posterolateral abdominal wall defects that may be congenital or acquired. There are two types of lumbar hernia, the superior lumbar hernia through Grynfeltt triangle, and the inferior lumbar hernia through Petit triangle. Many techniques have been described for the surgical repair of lumbar hernias including primary repair, local tissue flaps, and conventional mesh repair. But these open techniques require a large skin incision. We report a case of superior lumbar hernia, which was successfully repaired using a laparoscopic approach. PMID- 22319746 TI - Successful hybrid operation of an acute mobile thrombus in the abdominal aorta induced by chemotherapy. AB - Acute mobile thrombus of the abdominal aorta after chemotherapy is a very unusual finding, which can be a potential source of arterial embolism. We report here on a case of an acute mobile aortic thrombus with renal infarction. We successfully treated the patient with hybrid operation-open surgical and endovascular approach. Our case shows that hybrid treatment using wire-directed balloon catheter thrombectomy is a feasible, minimally-invasive treatment for a mobile aortic thrombus. PMID- 22319747 TI - Spontaneous left external iliac vein rupture. AB - We report a 72-year-old female patient with spontaneous rupture of the left external iliac vein. She visited our hospital for abdominal and back pain. She had the abnormal finding of hemoperitoneum. We performed an emergency operation with diagnosis of left ovarian cyst rupture though she suffered from spontaneous rupture of the left external iliac vein. This case provides insight to the experience of spontaneous rupture of the left external iliac vein. PMID- 22319748 TI - Choledochal cyst with ectopic distal location of the papilla of Vater. AB - In cholangiographic techniques, the close relationship between choledochal cyst and anomalous union of pancreaticobiliary duct has attracted medical attention. There have been rare cases in which the papilla of Vater was found in a position other than its normal position, and such cases have been reported sporadically. However, such cases are interesting in the anatomical context. In this review, we present our experience of choledochal cyst in a 30-month-old boy in whom the papilla of Vater was positioned in the third portion of the duodenum. PMID- 22319749 TI - Dental plaque biofilm in oral health and disease. AB - Dental plaque is an archetypical biofilm composed of a complex microbial community. It is the aetiological agent for major dental diseases such as dental caries and periodontal disease. The clinical picture of these dental diseases is a net result of the cross-talk between the pathogenic dental plaque biofilm and the host tissue response. In the healthy state, both plaque biofilm and adjacent tissues maintain a delicate balance, establishing a harmonious relationship between the two. However, changes occur during the disease process that transform this 'healthy' dental plaque into a 'pathogenic' biofilm. Recent advances in molecular microbiology have improved the understanding of dental plaque biofilm and produced numerous clinical benefits. Therefore, it is imperative that clinicians keep abreast with these new developments in the field of dentistry. Better understanding of the molecular mechanisms behind dental diseases will facilitate the development of novel therapeutic strategies to establish a 'healthy dental plaque biofilm' by modulating both host and microbial factors. In this review, the present authors aim to summarise the current knowledge on dental plaque as a microbial biofilm and its properties in oral health and disease. PMID- 22319750 TI - Using DGGE and 16S rRNA gene sequence analysis to evaluate changes in oral bacterial composition. AB - OBJECTIVE: To investigate whether a standard dental prophylaxis followed by tooth brushing with an antibacterial dentifrice will affect the oral bacterial community, as determined by denaturing gradient gel electrophoresis (DGGE) combined with 16S rRNA gene sequence analysis. METHODS: Twenty-four healthy adults were instructed to brush their teeth using commercial dentifrice for 1 week during a washout period. An initial set of pooled supragingival plaque samples was collected from each participant at baseline (0 h) before prophylaxis treatment. The subjects were given a clinical examination and dental prophylaxis and asked to brush for 1 min with a dentifrice containing 0.3% triclosan, 2.0% PVM/MA copolymer and 0.243% sodium fluoride (Colgate Total). On the following day, a second set of pooled supragingival plaque samples (24 h) was collected. Total bacterial genomic DNA was isolated from the samples. Differences in the microbial composition before and after the prophylactic procedure and tooth brushing were assessed by comparing the DGGE profiles and 16S rRNA gene segments sequence analysis. RESULTS: Two distinct clusters of DGGE profiles were found, suggesting that a shift in the microbial composition had occurred 24 h after the prophylaxis and brushing. A detailed sequencing analysis of 16S rRNA gene segments further identified 6 phyla and 29 genera, including known and unknown bacterial species. Importantly, an increase in bacterial diversity was observed after 24 h, including members of the Streptococcaceae family, Prevotella, Corynebacterium, TM7 and other commensal bacteria. CONCLUSION: The results suggest that the use of a standard prophylaxis followed by the use of the dentifrice containing 0.3% triclosan, 2.0% PVM/MA copolymer and 0.243% sodium fluoride may promote a healthier composition within the oral bacterial community. PMID- 22319751 TI - Effects of ethanol-wet bonding technique on root dentine adhesion. AB - OBJECTIVE: To investigate the effects of ethanol-wet bonding on the adhesion of experimental hydrophobic and commercial hydrophilic adhesives to root dentine. METHODS: A total of 43 single-rooted integrated human premolars were selected and sectioned. Of the 86 initially obtained specimens, 66 were randomly and equally divided into water-wet bonding and ethanol-wet bonding groups (n = 33). The specimens of each group were subdivided into three subgroups (n = 11) based on different adhesives: two experimental hydrophobic adhesives (Bis-GMA/TEGDMA, BT; and UDMA/TEGDMA, UT) and one commercial hydrophilic adhesive (AdperTM Single Bond 2, SB). The root surfaces were ground, acid-etched and rinsed and resin composite applied. After storing in distilled water for 24 h at 37 degrees C, the shear bond strength (SBS) of each specimen was measured. A sample from each subgroup was randomly selected and prepared for scanning electron microscopy (SEM) analysis. The remaining 20 specimens were used in the contact angle (CA) experiment, and the values of CA were measured. SBS was analysed with two-way ANOVA/Tukey's multiple comparison test and CA with independent sample t test. RESULTS: A significant increase in SBS to root dentine was observed in the ethanol-wet bonding group compared with the traditional water-wet bonding group. The experimental hydrophobic adhesives (UT group) with ethanol-wet bonding presented the highest SBS (22.44 +/- 3.32 MPa). CA increased significantly after the dentine surfaces were dried, especially for the water-saturated group. CONCLUSION: The adhesion to root dentine surfaces with ethanol-wet bonding may be superior to water-wet bonding. PMID- 22319752 TI - Changes in mRNA expression of adenosine receptors in human chronic periodontitis. AB - OBJECTIVE: To elucidate the aetiology of periodontitis, this study focused on the adenosine receptor (AR) expression profiles (A1AR, A2AAR, A2BAR and A3AR) in periodontal diseased tissues. METHODS: Adenosine receptor gene expression levels in human gingiva from 15 patients with healthy gingival tissues (control group) and 15 patients who exhibited severe chronic periodontitis (test group) were measured using quantitative reverse transcription-polymerase chain reaction (RT PCR). RESULTS: The mRNA expression pattern changed in human chronic periodontitis: the A1AR decreased 20%, A2AAR increased 2.5-fold, A2BAR increased 3.7-fold and A3AR decreased 70% as compared with that of healthy gingiva. CONCLUSION: Inflammation of the gingival tissue is associated with (1) an unchanged expression of A1AR, (2) an increased expression of A2AAR and A2BAR, and (3) a decreased expression of A3AR. Logistic regression analysis indicated that the change in the expression patterns can be used to diagnose/predict periodontitis. This finding indicates that the adenosine receptor expression profile is changed in periodontitis with the potential for future clinical application. PMID- 22319753 TI - Mineral trioxide aggregate versus calcium hydroxide for pulpotomy in primary molars. AB - OBJECTIVE: To compare the effects of mineral trioxide aggregate (MTA) and calcium hydroxide (CH) for pulpotomy in primary molars. METHODS: A randomised, bilateral self-controlled clinical trial was designed to compare the clinical effect of MTA and CH in pulpotomies in primary molars in 4- to 9-year-old children. Children with two similar-sized cavities on bilateral primary molar counterparts requiring pulpotomies were included. The two contralateral molars in each patient were randomly assigned to MTA or CH treatment. Clinical and radiographic examinations were performed to evaluate the treatment results at post-treatment recall. RESULTS: Seventeen pairs of self-controlled contralateral teeth were available for follow-up evaluations. The success rate of MTA was 94.1% (16/17), while the success rate of CH was 64.7% (11/17). Internal root resorption was the most frequent reason for failure in the CH group. Crown discolouration was common in the MTA-treated group. CONCLUSION: MTA was more successful than CH for pulpotomies in primary molar teeth, and may be a suitable replacement for CH in primary molar pulpotomies. PMID- 22319754 TI - Clinical survey of cervical tooth lesions in first-appointment patients. AB - OBJECTIVE: To investigate the relationship between cervical lesions and patient age, brushing method and bruxism based on a clinical survey of first-appointment patients. METHODS: Two hundred and nine patients (118 male, 91 female) who had unfilled cervical lesions were examined. Information on patient age, teeth with lesions, classification of the lesions, brushing method and bruxism was obtained. The data were analysed statistically. RESULTS: Cervical lesions started to develop in the first premolar teeth in the early twenties and became more prevalent with age. A habit of bruxism was associated with an increase in cervical lesions. Brushing was not directly associated with the development of cervical lesions. CONCLUSION: This study suggests that cervical lesions should be treated at an early stage to prevent further problems. PMID- 22319755 TI - Effects of chlorhexidine, listerine and fluoride listerine mouthrinses on four putative root-caries pathogens in the biofilm. AB - OBJECTIVE: To investigate the effects of chlorhexidine (CHX), Listerine and Fluoride Listerine on putative root-caries pathogens in the biofilm in the artificial mouth model. METHODS: A total of 24 human dentine discs were prepared. A biofilm composed of Streptococcus mutans, Streptococcus sobrinus, Lactobacillus rhamnosus and Actinomyces naeslundii was cultured on the surfaces of human dentine discs in an artificial-mouth model. Sucrose was supplied by computer controlled release on a daily basis to simulate the real-life situation. Three treatment reagents, CHX, Listerine and Fluoride Listerine, were supplied at a flow rate of 15 ml/h for 6 min twice a day. The dentine discs with biofilm were removed from the artificial mouth after being cultured for 1, 2, 3, 4, 5 and 6 days. The bacteria in the biofilm were analysed by plating on BHIS agar and the colony-forming units of each species were counted. RESULTS: The total number of bacteria in the CHX group was significantly lower than in the other three groups (including control). There was no decline in the number of bacteria in the Listerine group. S. mutans was reduced significantly in the CHX group compared with the control group. The number and proportion of A. naeslundii in the CHX group were significantly lower than in the other three groups. The proportion of L. rhamnosus in the CHX group was significantly higher than in the other three groups. CONCLUSION: CHX has the most significant effect on inhibition of the putative root-caries bacteria, with the exception of L. rhamnosus. Both Listerine and a combination of fluoride and Listerine could not effectively reduce the numbers of bacteria in the biofilm. The effects of CHX, Listerine and Fluoride Listerine on root caries prevention need further investigation. PMID- 22319756 TI - Radiologic investigation of prevalence, associated pathologies and dental anomalies of non-third molar impacted teeth in Turkish oral patients. AB - OBJECTIVE: To investigate the prevalence and associated pathologies of impacted teeth in Turkish oral patients. METHODS: A retrospective survey was carried out in 12,129 patients who visited the Department of Oral Diagnosis and Radiology, Ondokuz Mayis University, Faculty of Dentistry, Turkey, from January 2003 to December 2007. The minimum age for inclusion was 14 years and third molar impactions were excluded from the study. To be enrolled in the study, the patient's chart had to contain a panoramic radiograph with supplemental periapical radiographs. One radiologist examined all radiographs to determine the number, orientation and types of impacted teeth and the presence of associated pathologies and developmental dental anomalies associated with this phenomenon. RESULTS: Of the 12,129 patients, 1117 (9.2%) patients aged 14 to 80 years had one or more dental impactions (in total 1356 impacted teeth). The male to female ratio was 1:1.4 (457:660). The maxillary canine teeth were the most commonly encountered (71.5%), followed by the mandibular premolars (8.6%). The analysis of the orientation of the impacted teeth showed that 480 impacted teeth were in a mesioangular position (35.4%), followed by vertical (28.9%), distoangular (18.9%), horizontal (16.5%) and buccolingual (0.3%) orientations. CONCLUSION: The prevalence of non-third molar impacted teeth was 9.2% among Turkish oral patients. The maxillary canines were the most frequent impacted teeth. The most common orientations of impacted teeth were the mesioangular position and vertical orientation. The most frequent associated pathologic change was cystic change. PMID- 22319757 TI - Open reduction and rigid internal fixation of dislocated condylar fractures: a long-term follow-up of 25 patients. AB - OBJECTIVE: To evaluate the long-term results of open reduction and rigid internal fixation for treatment of dislocated condylar process fractures. METHODS: Twenty five patients with dislocated condylar fracture who underwent open reduction and rigid internal fixation were followed up for an average of 4.5 years and evaluated on the basis of occlusion, temporomandibular joint (TMJ) function and radiographs. RESULTS: Clinically, both occlusion and TMJ function were satisfactory. Generally, the dislocated condyles were well repositioned into the glenoid fossa after rigid internal fixation and remained in the position during the follow-up on the radiographs. CONCLUSION: Open reduction and rigid internal fixation could achieve satisfactory results for the treatment of dislocated condylar fractures. PMID- 22319758 TI - A case report of six canals in a maxillary first molar. AB - Identifying the variations of root canal morphology is crucial prior to commencing any endodontic treatment. The advancement of current endodontic instrumentation and technology has greatly enhanced treatment outcomes, which are now more predictable. This clinical case report presents a case of a maxillary first molar showing six root canals and apical foramina, i.e. three mesiobuccal canals, two palatal canals and one distobuccal canal. The occurrence of bifurcation in the second mesiobuccal canal is also emphasised. PMID- 22319759 TI - Diagnosis and treatment of a hereditary gingival fibromatosis case. AB - Hereditary gingival fibromatosis (HGF) is a rare condition characterised by severe gingival hyperplasia, which could result in serious aesthetic and emotional problems and functional impairment. Here the present authors report a case of a 28-year-old female patient with generalised severe gingival enlargement covering almost all of the teeth and diagnosed as HGF. Her family history was of significance, since her father and 3-year-old daughter suffered from the same symptoms. Many studies have agreed that surgical removal should be used in the treatment of HGF, and gingivectomy is the most common method. This study tried both external and internal bevel incisions. The results suggest that the former is better for shaping gingival contour, if the attached gingiva is adequate. Correct physiological contour of the marginal gingiva, good oral hygiene and periodic recall can decrease recurrence risk. Post-surgical follow-up after 26 months demonstrated no recurrence and the patient was satisfied with her appearance. PMID- 22319760 TI - The seven year itch. PMID- 22319761 TI - Minimally invasive restoration of a maxillary central incisor with a partial veneer. AB - Minimally invasive treatment modalities allow for the preservation of sound tooth substance. However, by limiting the preparation to the extent of a defect, the transition between restoration and natural tooth may be moved to more visible areas. The materials available for the restoration of a limited defect in the anterior area are either resin composite materials or porcelain. A patient was presented who asked for the replacement of a discolored filling on the maxillary right central incisor. Tooth preparation was limited to the extent of the old filling, and a porcelain partial veneer restoration was fabricated. Despite the horizontal finish line in the middle of the clinical crown, a result could be achieved that was regarded as a success by the patient. This type of restoration proves to be a suitable alternative to direct composite restorations in the anterior area for the reconstruction of a limited defect, eg, due to a dental trauma. PMID- 22319762 TI - Multidisciplinary treatment plans in the adult patient - step by step and rationale. AB - Interdisciplinary, multidisciplinary and comprehensive treatment plans are now part of everyday practice. The interaction between different specialists can provide patients with better, more conservative and more pleasing results. This case report shows the step by step of a multidisciplinary treatment plan and the rationale for each part of a process where conservative dentistry, periodontics, orthodontics, implant dentistry and prosthetics are involved. PMID- 22319763 TI - Soft tissue remodeling technique as a non-invasive alternative to second implant surgery. AB - It is currently accepted that success in implant-supported restorations is based not only on osseointegration, but also on achieving the esthetic outcome of natural teeth and healthy soft tissues. The socalled "pink esthetic" has become the main challenge with implant-supported rehabilitations in the anterior area. This is especially difficult in the cases with two adjacent implants. Two components affect the final periimplant gingiva: a correct bone support, and a sufficient quantity and quality of soft tissues. Several papers have emphasized the need to regenerate and preserve the bone after extractions, or after the exposure of the implants to the oral environment. The classical implantation protocol entails entering the working area several times and always involves the surgical manipulation of peri-implant tissues. Careful surgical handling of the soft tissues when exposing the implants and placing the healing abutments (second surgery) helps the clinician to obtain the best possible results, but even so there is a loss of volume of the tissues as they become weaker and more rigid after each procedure. The present study proposes a new protocol that includes the connective tissue graft placement and the soft tissues remodeling technique, which is based on the use of the ovoid pontics. This technique may help to minimize the logical scar reaction after the second surgery and to improve the final emergence profile. PMID- 22319764 TI - Inlay-retained zirconia fixed dental prosthesis: clinical and laboratory procedures. AB - Many treatment options are currently available for single tooth replacement, such as metal-ceramic, all-ceramic, direct or indirect fiber-reinforced composite fixed dental prostheses (FDPs) or implants. Inlay-retained FDPs could be indicated especially when adjacent teeth have preexisting restorations and where implant placement is not possible or not indicated. In such cases, indication of both metal-ceramic and fiber-reinforced composite FDPs has certain disadvantages. This paper describes the use of all-ceramic inlay-retained FDPs with zirconia frameworks, veneered with a press-on technique. The retainer margins were made of pressed ceramic to make adhesive luting possible. In deep cavities, a full contour press-on ceramic all around the retainers increased the available surface area for the adhesive approach. PMID- 22319765 TI - Therapeutic effectiveness of a new enzymatic bleaching dentifrice. AB - BACKGROUND: Research into bleaching focuses on new products in order to minimize undesirable effects. This study evaluated the bleaching effectiveness of a new enzymatic-activated dentifrice. MATERIALS AND METHODS: A total of 20 volunteers were bleached with a dentifrice containing 5% lactoperoxidase and 3% carbamide peroxide applied three times a day for two minutes over 21 days. Color was recorded before and after the treatment using a spectrophotometer. CIELAB differences were calculated before and after treatment using the paired t test (P < 0.05). RESULTS: Lightness was significantly higher after treatment (P < 0.001), DeltaE was 5.14. The maxillary central incisors showed greater lightness than the laterals and canines, both before and after treatment, and a greater tendency towards green and blue; the same occurred in the mandibular central incisors in comparison to the canines and laterals. CONCLUSIONS: The use of brush-applied enzyme-activated carbamide peroxide at low concentrations with short exposure time is effective for whitening teeth. CLINICAL IMPLICATIONS: Enzymatic dental bleaching is able to increase the efficiency of low concentration peroxides, reducing the potential risk of peroxides on oral tissues. PMID- 22319766 TI - Surface characterization of SLActive dental implants. AB - The aim of the study was to characterize the surface chemistry, hydration capacity, topography and roughness of the root part of a hydrophilic sandblasted and acid-etched titanium dental implant (SLActive). Implants as received (SAR), after water rinsing (SAW) and after ultrasonication in water (SAU) were subjected to x-ray photoelectron spectroscopy (XPS) elemental and binding state analysis. Scanning electron microscopy plus energy dispersive x-ray microanalysis (SEM/EDX), reflection Fourier transform infrared microspectroscopy (RFTIRM) and hydration/ dehydration cycling by environmental scanning electron microscopy (ESEM), were performed in SAR, whereas SAU implants were subjected to 3D-optical profilometry and SEM. For all the experiments, a conventional sandblasted and acid-etched implant (SLA ) of the same manufacturer was used as control. XPS showed lower mean C content in SAR than SLA, but not significantly different. In SAW, the C and O contents were increased. Significantly reduced C and increased Ti and O contents were found in SAU. Residual Na phases, other than NaCl, were traced in all SLActive groups. SAR demonstrated higher [-OH]/O2- ratio than SLA . EDX documented higher O, Na, Cl and lower Ti content in SAR. More -OH contributions were probed on SAR in comparison with SLA by RFTI RM. Ti-O peaks assigned to anatase, rutile and amorphous phases were found in both implant groups. The ESEM study revealed a full rehydration capacity in SAR, in contrast to SLA. No differences were found in the topography of SAU and SLA implant surfaces under the SEM. However, significantly greater values in spatial and functional roughness parameters were encountered in SAU. The increased surface hydroxylated titanium content and the greater spatial and functional roughness parameters, may explain the enhanced biological activity documented for SLActive in comparison with SLA. PMID- 22319767 TI - Harvesting the biosphere: the human impact. AB - The human species has evolved to dominate the biosphere: global anthropomass is now an order of magnitude greater than the mass of all wild terrestrial mammals. As a result, our dependence on harvesting the products of photosynthesis for food, animal feed, raw materials, and energy has grown to make substantial global impacts. During the past two millennia these harvests, and changes of land use due to deforestation and conversions of grasslands and wetlands, have reduced the stock of global terrestrial plant mass by as much as 45 percent, with the twentieth-century reduction amounting to more than 15 percent. Current annual harvests of phytomass have been a significant share of the global net primary productivity (NPP, the total amount of new plant tissues created by photosynthesis). Some studies put the human appropriation of NPP (the ratio of these two variables) as high as 40 percent but the measure itself is problematic. Future population growth and improved quality of life will result in additional claims on the biosphere, but options to accommodate these demands exist without severely compromising the irreplaceable biospheric services. PMID- 22319768 TI - Comparing relative effects of education and economic resources on infant mortality in developing countries. AB - Research on the social determinants of health has often considered education and economic resources as separate indicators of socioeconomic status. From a policy perspective, however, it is important to understand the relative strength of the effect of these social factors on health outcomes, particularly in developing countries. It is also important to examine not only the impact of education and economic resources of individuals, but also whether community and country levels of these factors affect health outcomes. This analysis uses multilevel regression models to assess the relative effects of education and economic resources on infant mortality at the family, community, and country level using data from demographic and Health Surveys in 43 low-and lower-middle-income countries. We find strong effects for both per capita gross national income and completed secondary education at the country level, but a greater impact of education within families and communities. PMID- 22319769 TI - Son preference in rural China: patrilineal families and socioeconomic change. AB - This article draws on a survey conducted in six provinces in summer 2008 to investigate the determinants of son preference in rural China. The analysis confirms the conventional wisdom that son preference is embedded within patrilineal family structures and practices. We extend our analysis by exploring specific aspects of variation within patrilineal family culture. We find that the patrilineal group (clan) composition of villages and family participation in practices such as building ancestral halls and updating genealogies significantly influence son preference. Yet even though son preference is embedded within patrilineal family culture, our analysis suggests that over time the attenuation of son preference is likely. This is because determinants associated with socioeconomic change-for instance, higher levels of education, direct exposure to official policy education materials, higher income (a proxy for rural industrialization), and agricultural mechanization-all attenuate son preference. Being younger and female are also associated with weaker son preference, and both characteristics are likely to interact with education and industrialization to further dilute son preference in the longer term. Nevertheless, our findings suggest that concerted efforts are needed to ameliorate institutional discrimination against rural people in welfare provisioning and in labor markets, and to promote multiple dimensions of gender equality, including in land rights, wage rates, and education. PMID- 22319770 TI - Economic inequality and child stunting in Bangladesh and Kenya: an investigation of six hypotheses. AB - Consistent with the increasing focus on issues of equity in developing countries, I extend the literature analyzing the relationship between economic inequality and individual health to the developing world. Using survey data from Bangladesh and Kenya with economic status measured by a wealth index and with three different geographic definitions of community, I analyze six competing hypotheses for how economic inequality may be related to stunting among children younger than 5 years old. I find little support for the predominant hypothesis that economic inequality as measured by a Gini index is an important predictor of individual health. Instead, I find that the difference between a household's wealth and the mean household wealth in the community is the measure of economic inequality that is most closely related to stunting in these countries. In particular, a 1 standard deviation increase in household wealth relative to the community mean is associated with a 30-32 percent decrease in the odds of stunting in Bangladesh and a 16-21 percent decrease in the odds of stunting in Kenya. PMID- 22319771 TI - Population momentum across the demographic transition. AB - Population momentum is the main driver of global population growth today, and this makes an appreciation of momentum critical to understanding contemporary worldwide growth dynamics. This article traces population momentum along with two recently defined measures of momentum decomposed-stable and nonstable momentum across the demographic transition. We use historical data and population projections from 16 countries to illustrate some previously ignored empirical regularities of the demographic transition in both the developed and the developing world. We also demonstrate the dynamic nature of stable and nonstable momentum, as changes in stable momentum lead to predictable changes in current and future nonstable momentum. These results suggest that momentum, which by definition is measured at a point in time, can also be considered as a process that unfolds over time. PMID- 22319772 TI - The association of television and radio with reproductive behavior. AB - This note analyzes the association between media exposure and reproductive behavior in 48 developing countries. A summary of part of a more extensive Demographic and Health Surveys report, it shows strong connections between media exposure and the use of modern contraception, the number of children desired, and recent fertility. Television viewing is particularly important; it is assumed to expose viewers to aspects of modern life that compete with traditional attitudes toward the family and is associated with greater use of modern contraceptive methods, with a desire for fewer children, and with lower fertility. These relationships are particularly noteworthy because the data measure only the frequency of media exposure with no information about its content. PMID- 22319773 TI - The impact of the HIV/AIDS epidemic on kinship resources for orphans in Zimbabwe. AB - The extended family has been recognized as a major safety net for orphans in sub Saharan Africa. However, the mortality crisis associated with HIV/AIDS may drastically reduce the availability of relatives and thus undermine traditional forms of mutual support. In this article, the microsimulator SOCSIM is used to estimate and project quantities such as the number of living uncles, aunts, siblings, and grandparents available to orphans. The model is calibrated to the setting of Zimbabwe, using data from demographic and Health Surveys and estimates and projections of demographic rates from the United Nations. The article shows that there is a lag of more than ten years between the peak in orphanhood prevalence and the peak in scarcity of grandparents for orphans. The results indicate that a generalized HIV/AIDS epidemic has a prolonged impact on children and orphans that extends well beyond the peak in mortality. A rapid increase in the number of orphans is followed by a steady reduction in the number of living grandparents for orphans. Consequently, the burden of double orphans (both of whose parents have died) is likely to shift to uncles and aunts. In Zimbabwe, the number of living uncles and aunts per double orphan decreased between 1980 and 2010, but it is expected to increase progressively during the next few decades. Changes in kinship structure have important social consequences that should be taken into account when seeking to address the lack of care for orphans. PMID- 22319775 TI - Retraction. Roy B, Bose A, Bhaumik U, Das A, Chatterjee N, Ghosh A, Darbar S, Sarkar AK, Sengupta P, Pal TK. 2010. Convulsant activity and pharmacokinetic pharmacodynamic modeling of the electroencephalogram effect of gemifloxacin in rats. J Pharm Sci 99:1535-1547. PMID- 22319777 TI - Abstracts of the 101st Annual Meeting of the United States and Canadian Academy of Pathology. March 17-23, 2012, Vancouver, British Columbia, Canada. PMID- 22319776 TI - The sensory field and repeatability of the cutaneous trunci muscle reflex of the dog. AB - OBJECTIVE: To describe the cutaneous trunci muscle (CTM) reflex in dogs. STUDY DESIGN: Prospective descriptive study. ANIMALS: Normal dogs (n = 155) and 10 dogs with thoracolumbar myelopathies. METHODS: The CTM reflex caudal border was assessed from the ilial crests moving cranially until a CTM contraction was elicited. The lateral borders were evaluated at 4 levels and the distance from the midline to the lateral border was expressed asa percentage of the trunk hemicircumference. The caudal border was assessed in 10 dogs with myelopathies by 4 different observers and by 1 observer on 3 occasions;the inter- and intraobserver kappa coefficient was calculated. RESULTS: The CTM reflex was elicited in all dogs. Its caudal border was at L5 or L6 in 153 dogs and at L1 and L3 in 2 dogs. The lateral field of the reflex occupied>50%of the hemicircumference of the trunk at each level tested. The mean difference in measurement of the reflex caudal border was 0.55 cm between observers and 0.28 cm for the same observer. The inter- and intraobserver kappa coefficient was 0.67 and 0.87, respectively. CONCLUSIONS: The CTM reflex is elicited caudal to L5 in most normal dogs, and the lateral sensory field extends to 50% or more of the circumference of the trunk.Inter- and intraobserver differences in assessment of the caudal border are low. PMID- 22319779 TI - Abstracts of the 101st Annual Meeting of the United States and Canadian Academy of Pathology . March 17-23, 2012. Vancouver, British Columbia, Canada. PMID- 22319778 TI - Comparison of femoral angulation measurement between radiographs and anatomic specimens across a broad range of varus conformations. AB - OBJECTIVE: To determine if measurement of anatomic lateral distal femoral angle (aLDFA) from radiographs is valid across a broad range of femoral varus conformations. STUDY DESIGN: Radiographic and anatomic study. SAMPLE POPULATION: Large breed canine cadavers (n = 5) and femora (n = 10). METHODS: Cadavers were held in dorsal recumbency and 8 craniocaudal radiographic projections made of each femur: 1 image pre- and postosteotomy and at each of 6 progressive levels of induced distal varus deformity. Femurs were collected. Three blinded examiners independently measured varus on each radiograph (R-aLDFA) and femoral specimen (S aLDFA) on 3 separate occasions. Intra- and interobserver variance in R-aLDFA and S-aLDFA measurements were determined. The strength of relationship between R aLDFA and S-aLDFA and positive and negative predictive values for R-aLDFA were calculated. CONCLUSION: Intra- and interobserver variance in R-aLDFA (mean, 0.54% and 0.40%, respectively) and S-aLDFA (mean, 0.43% and 0.41%, respectively) were acceptable. The strength of relationship between R-aLDFA and S-aLDFA (adjusted R2 = 78.2%) was marginally below the acceptance criterion of 80%. Using aLDFA >= 102 degrees as an indication for corrective femoral osteotomy, radiography was successful in correctly identifying corrective femoral osteotomy candidates (positive predictive value) and noncandidates (negative predictive value) 72% and 96% of the time, respectively. PMID- 22319780 TI - Live and let die: a new suicide gene therapy moves to the clinic. PMID- 22319781 TI - Distinct role of calmodulin and calmodulin-dependent protein kinase-II in lipopolysaccharide and tumor necrosis factor-alpha-mediated suppression of apoptosis and antiapoptotic c-IAP2 gene expression in human monocytic cells. PMID- 22319783 TI - Cyclosporin A and FK506 inhibit IL-12p40 production through the calmodulin/calmodulin-dependent protein kinase-activated phosphoinositide 3 kinase in lipopolysaccharide-stimulated human monocytic cells. PMID- 22319782 TI - Activation of JNK-dependent pathway is required for HIV viral protein R-induced apoptosis in human monocytic cells. Involvement of antiapoptotic BCL2 and c-IAP1 genes. PMID- 22319784 TI - HIV-1 Nef inhibits lipopolysaccharide-induced IL-12p40 expression by inhibiting JNK-activated NFkappaB in human monocytic cells. PMID- 22319786 TI - A research institute at a turning point. Interview by Kathryn Claiborn. PMID- 22319787 TI - The true nature of alpha-synuclein unmasked! PMID- 22319788 TI - Dual left anterior descending coronary artery diagnosed with 128-slice dual source CT. PMID- 22319789 TI - The investigation of binary PPIs with the classical yeast two-hybrid (Y2H) approach, Y2H variants, and other in vivo methods for PPI mapping. PMID- 22319790 TI - Recognition of faciobrachial dystonic seizures allowing early intervention with and prevention of development of full-blown limbic encephalitis. PMID- 22319791 TI - Links between glucocerebrosidase and alpha-synuclein revealed. PMID- 22319792 TI - Learning PD from the lark. PMID- 22319793 TI - Minocycline-induced hyperpigmentation. PMID- 22319794 TI - When parents do not want their daughters on birth control pills: tips for navigating a difficult clinical situation. PMID- 22319795 TI - Image of the month: an unusual case of metastatic malignant melanoma. PMID- 22319796 TI - Image of the month: mouse colon staining. PMID- 22319811 TI - Place attachment among retirees in Greensburg, Kansas. AB - On 4 May 2007 an ef-5 tornado leveled 95 percent of Greensburg, Kansas. Because city leaders encouraged everyone to use "green" building techniques as they rebuilt their homes and businesses, not only has the return to normalcy been exceedingly slow, but some of the town's older residents feel that officials have overlooked their needs. These minor episodes of discord enabled us to learn what features are most important to people in retirement. The features include identifiable landmarks, a space in which to socialize, and age-specific businesses. We assert that the lessons learned in Greensburg are applicable to other communities with a sizable older population. As baby boomers rapidly enter retirement they will seek places to live that are elder friendly and enable them to effectively bond with place. As previous research attests, people who have a strong attachment to place commonly have a good quality of life. PMID- 22319812 TI - Making scents of transition: smellscapes and the everyday in "old" and "new" urban Poland. AB - In this article, the growing body of literature on transition within central and eastern Europe is developed by exploring how discussing the senses may illuminate the experience of change to post-socialism for urban dwellers. After situating the study within the rich ethnographic heritage on urban transition, the key tenets of 'geographies of smell' are outlined as a means of inquiry which emphasises the lived, sensually embodied experience of transition. The empirical study is focused upon the interrogation of the meanings created by, and attached to, olfactory experience in contemporary Poland, discussing three motifs that highlight the symbolic and transformative role of smell in relation to transition. In understanding smell as playing an active role in the creation of meaning, not only are current debates surrounding geographies of smell extended, but it is argued that addressing the relatively neglected sensual dimension of the social provides an avenue into more nuanced dimensions of urban transition. PMID- 22319813 TI - Neighbourhood disorder and social cohesiveness among immigrants in a new destination: Dominicans in Reading, PA. AB - Dominican immigrants are increasingly turning away from traditional metropolitan gateways to settle in relatively small and medium-sized cities in the Northeast US. This study examines their views about neighbourhood social disorder and cohesiveness in Reading, Pennsylvania. The results indicate that residents are divided about the pervasiveness of disorder-related problems in their neighbourhoods. Moreover, views about social disorder have implications for social cohesiveness, but neither of these dimensions of urban life can be understood apart from immigrant incorporation. Among those who live in areas without disorder, naturalised citizens are especially likely to feel that they live in a tight-knit neighbourhood and to interact with neighbours. The study concludes with an examination of perceptions of neighbourhood safety. PMID- 22319815 TI - Pharmaceutical high profits: the value of R&D, or oligopolistic rents? AB - Pharmaceutical firms attribute high prices and high profits to costs associated with researching and developing the next generation of life-saving drugs. Using data from annual reports, this article tests the validity of this claim. We find that while pharmaceutical firms do invest in R&D, they also enjoy strong rents; between 1988 and 2009, pharmaceuticals enjoyed profits of 3 to 37 times the all industry average, depending on the years, while investing proportionately less in R&D than other high-R&D firms. Costs of pharmaceutical drugs have successfully flown below the radar in much of the current health care debate, with producers managing to obstruct alternative sourcing as well as payment cuts. While health care is examined for savings in other areas, sustained high pharmaceutical profits suggest that as a new health care policy develops in the U.S., the pharmaceutical industry should not be excluded from examination for significant savings in health care costs. PMID- 22319816 TI - Treatment. Individual approach needed for co-infections. PMID- 22319817 TI - Research. Topical anal microbicide reduces risk of HIV transmission in trial. PMID- 22319818 TI - Policy. Routine testing, increased funding essential in HIV fight. PMID- 22319819 TI - Expand focus when addressing sexual health of MSM. PMID- 22319820 TI - Court orders disclosure of man's HIV-related medical records. PMID- 22319821 TI - Exposure. Class certification denied, man lacks standing to represent. PMID- 22319822 TI - Housing. Woman removed from facility for HIV, not incontinence. PMID- 22319823 TI - SSI. Court affirms ALJ's ruling denying benefits to man with HIV. PMID- 22319824 TI - Angioplasty a day after a heart attack not worth it. Medical therapy is better for late treatment. PMID- 22319825 TI - Preventing pacemaker, ICD infections now a priority. If one occurs, early detection and immediate action are crucial. PMID- 22319826 TI - Putting heart attack, stroke triggers in perspective. The brief boost in risk usually doesn't linger. PMID- 22319827 TI - Beta blockers: cardiac jacks of all trades. Uses for beta blockers range from lowering blood pressure to improving heart failure. PMID- 22319828 TI - Ask the doctor. My doctor recently put me on Tenormin because my blood pressure was getting high. Now, when I run or row, I can't get my heart rate much above 115 beats per minute even though my peak heart rate should be 136. Is the beta blocker keeping me from getting the full benefit of exercise? PMID- 22319829 TI - Healthy Eating Plate dishes out sound diet advice. More specific than MyPlate, it pinpoints the healthiest food choices. PMID- 22319830 TI - Leg workouts improve exercise capacity in people with heart failure. PMID- 22319831 TI - Just-in-case electrocardiogram not recommended. PMID- 22319832 TI - Any exercise better than none to thwart peripheral artery disease. PMID- 22319833 TI - Ask the doctor. You've emphasized that people generally eat too much sodium and not enough potassium. Could I solve both problems at once by replacing my regular table salt with a substitute containing potassium? PMID- 22319834 TI - Ask the doctor. I come from a long line of family members with heart disease. Right now, my HDL is 62 mg/dL [milligrams per deciliter], and my LDL is 115 mg/dL. My doctor isn't worried about my LDL, but shouldn't I shoot for an LDL level under 100mg/dL? PMID- 22319835 TI - [Current status on screening for breast cancer]. PMID- 22319836 TI - [Breast cancer-local treatment-]. PMID- 22319837 TI - [Chemotherapy for breast cancer]. PMID- 22319838 TI - [Diagnosis of sleep-disordered breathing]. PMID- 22319839 TI - FDA denies petitions to restrict livestock drug use. PMID- 22319840 TI - Putting the science into science-based medicine. PMID- 22319841 TI - Texas court says pet dog has sentimental value. PMID- 22319843 TI - IJME's 20th year: some new directions. PMID- 22319842 TI - The reliability of American Board of Family Medicine examinations: implications for test takers. PMID- 22319844 TI - The legacy of scandals and non-scandals in research and its lessons for bioethics in India. PMID- 22319845 TI - MCI's VISION 2015 and PG medical selection: continuing to produce square pegs for round holes? PMID- 22319846 TI - International collaborative trials, placebo controls and The Declaration of Helsinki: need for clarification in paragraph 32. AB - Inequities in socio-economic and healthcare systems between developed and developing countries have been thrown into sharp relief by globalisation. At the same time, pharmaceutical companies have started conducting clinical trials in developing countries in order to reduce their costs substantially. Together, these two developments create ethical challenges for sponsors and researchers of these trials. One such challenge is that of placebo-controlled trials (PCTs). In this paper we analyse Paragraph 32 of the Declaration of Helsinki referring to PCTs, identifying ambiguities in the wording, and then examine three arguments presented by sponsors of PCTs in developing countries, in defence of such trials. These arguments are: (i) a placebo control provides a definitive answer, and is therefore methodologically superior; (ii) placebo-controlled trials are ethical because they serve the principle of utility, and (iii) interpreting the "best current proven intervention" as the local standard of care allows PCTs to be conducted, if the local standard of care is "no treatment". We argue that PCTs are not methodologically superior; nor are they ethically defensible. Other trial designs conforming to the ethics of research are feasible; the reason for conducting PCTs is expediency. We further propose that, given the global applicability of the Declaration of Helsinki, it is imperative to remove the ambiguities in Paragraph 32. In the context of collaborative trials, when a treatment exists, conducting PCTs is ethically unacceptable, irrespective of the geographic location of the trial. Universal standards ought to be applied universally. PMID- 22319847 TI - Less equal than others? Experiences of AYUSH medical officers in primary health centres in Andhra Pradesh. AB - The National Rural Health Mission (NRHM) includes, inter alia, the establishment of an AYUSH (Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homoeopathy) component (practitioner, trained assistants, drugs and equipment) in every primary health centre (PHC). However, five years following the launch of the NRHM, the AYUSH mainstreaming scenario is below expectations, riddled with ethical and governance issues. Accounts from AYUSH practitioners at PHCs in various regions of the state of Andhra Pradesh reveal enormous lacunae in implementation: unfilled positions, inequitable emoluments, inadequate or absent infrastructure, assistance and supplies, unethical interpersonal arrangements, and limited support from non-AYUSH personnel. The widespread negative impact of these conditions undermines the value of AYUSH, demotivating both practitioners and patients, and failing to provide the intended support to the public health system. PMID- 22319848 TI - Continuing oversight through site monitoring: experiences of an institutional ethics committee in an Indian tertiary-care hospital. AB - WHO-TDR and the Indian Council of Medical Research recommend site visits by institutional ethics committees (IECs) for continued oversight, to ensure the ethical conduct of research. Our IEC conducted seven site visits in 2008-2009 using a standardised format to monitor adherence to protocol and the informed consent process. The study identified issues related to informed consent (6/7), deviation from protocol (5/7), reporting of study progress to the IEC (3/7), recruiting additional participants without IEC approval (2/7), reporting of serious adverse events (1/7), investigator's lack of awareness of protocol and the informed consent document (2/7) and other findings. Investigators were informed about the findings and were asked to submit an explanation. The IEC issued warnings about not repeating such lapses in the future (5/7), restricted enrollment of new participants (2/7), recommended continued good clinical practice training to the study team (4/7), advised the recruitment of additional study coordinators (2/7), and requested the submission of adverse event reports (2/7) or sponsors' audit reports (2/7). Our study showed that the ethical conduct of studies can be ensured by conducting routine site monitoring. PMID- 22319849 TI - Finding and using evidence that you can trust. AB - Much of the evidence-base from research is biased. Systematically assembled, quality-appraised, and appropriately summarised reviews of the effects of interventions from all relevant intervention studies are needed, in order to use research evidence to reliably inform health decisions. The Cochrane Library is an online collection of six searchable, up-to-date, evidence-based databases that is available free to access by anyone in India, thanks to a national subscription purchased by the Indian Council of Medical Research. This valuable resource contains the world's single largest collection of systematic reviews and controlled clinical trials, as well as bibliographic details and records of methodological research, health technology assessments and economic analyses. The robust and transparent methods pioneered and used in Cochrane systematic reviews, and independence from industry funding facilitate the detection of biased, deceptive and fraudulent research, and have earned these reviews the reputation of being trusted sources of evidence to inform health decisions. Cochrane reviews have had considerable impact on academic medicine; have informed health practices, policies and guidelines; improved health outcomes; and saved numerous lives. PMID- 22319850 TI - Hunger, ethics and the right to food. AB - The management of hunger has to look into the issues of availability, accessibility and adequacy of food supply. From an ethical perspective, this paper argues in favour of the right to food. But, for this to become viable, the state has to come up with an appropriate and effective bill on food and nutrition security, address the issue of inadequate provisioning of storage space by state agencies leading to rotting of food grains--a criminal waste when people are dying of hunger; and rely on local level institutions involving the community, that complement the administrative structure to identify the poor and reduce exclusion and inclusion errors. PMID- 22319851 TI - Attempts at regulation of medical education by the MCI: issues of unethical and dubious practices for compliance by medical colleges and some possible solutions. PMID- 22319852 TI - Disability certificates in India: a challenge to health privacy. AB - A "disability certificate" is necessary to access benefits afforded under the Persons with Disabilities Act (1995) in India. This paper analyses this requirement and concludes that it constitutes a major challenge to maintaining privacy of health information especially for persons with mental health disabilities in India and recommends modifications in the certificate's format and use, to reduce the magnitude of privacy infringement for those using the disability certificate to access benefits to which they are legally entitled. PMID- 22319853 TI - Ethical aspects of public health legislation: the Mental Health Care Bill, 2011. AB - A legal framework is essential to promote and safeguard the interests of persons with mental illness. Since the Indian Lunacy Act, 1912, mental health legislation has come a long way. Currently efforts are underway to modify the existing Mental Health Act taking into account the resolutions under the UN Convention on the Rights of Persons with Disabilities. The proposed Mental Health Care Bill, 2011 incorporates promising modifications, like "caregiver", "nominated representative", "consent", "support" for decision making, and "advance directive" for persons with mental illness in its rubric, which seems potentially beneficial to the patients. The proposed new bill should facilitate and strengthen a mental health policy which provides acceptable, accessible, and equitable mental health care. A law becomes meaningful when it is realistic, implementable and ethical in provisions. In this comment, we take a critical look at the proposed 'The Mental Health Care Bill, 2011' through the lens of ethical principles. PMID- 22319854 TI - Observational study of cervical cancer. PMID- 22319855 TI - Knowledge vs ethics in clinical research in resource-poor settings: a clinician's perspective. PMID- 22319856 TI - Lost opportunities. PMID- 22319857 TI - Observational research where it is most needed. PMID- 22319858 TI - Some ethical issues here: demands of informed consent and ethical justification for research. PMID- 22319859 TI - William Osler's medical ethics in the 21st century. PMID- 22319860 TI - Universal immunisation programme. PMID- 22319861 TI - Saving lives, or styling them? PMID- 22319862 TI - Ethics in animal experiments. PMID- 22319863 TI - Bridging the ethics gaps. PMID- 22319864 TI - Through a nurse's eyes. PMID- 22319865 TI - Studies on seed germination and growth in weed species of rice field under salinity stress. AB - An investigation was made to see the salt tolerance of 10 weed species of rice. Properly dried and treated seeds of weed species were placed on 9 cm diameter petridishes lined with Whatman No. 1 filter paper under 6 salinity regimes, viz. 0 (control), 4, 8, 16, 24 and 32 dS m(-1). The petri dishes were then kept in germinator at 25 +/- 1.0 degrees C and 12 hr light. The number of germinated seeds were recorded daily. The final germination percentage, germination index (GI), seedling vigour index, mean germination time and time for 50% germination were estimated. Root and shoot lengths of the weed seedlings were measured at 20 days after salt application and relative growth values were calculated. Results revealed that salinity decreased final germination percentage, seed of germination as measured by GI, and shoot and root length in all the species. Germination of most of the weed seeds was completely arrested (0) at 32 dS m(-1) salinity except in E. colona (12%) and C. iria (13.9%). The species C. iria, E. colona, J. linifolia and E. crusgalli showed better germination (above 30%) upto 24 dS m(-1) salinity level and were regarded as salt-tolerant weed species. J. linifolia, F. miliacea, L. chinensis and O. sativa L. (weedy rice) were graded as moderately tolerant and S. zeylanica, S. grosus and C. difformis were regarded as least tolerant weed species. PMID- 22319866 TI - Community structure of earthworms under rubber plantations and mixed forests in Tripura, India. AB - Studies on community structures of earthworms of rubber (Hevea brasiliensis) plantations and their adjacent mixed forests in West Tripura (India) revealed that both the studied sites harvoured 10 earthworm species. Nine species (Pontoscolex corethrurus, Kanchuria sp 1, Metaphire houlleti, Drawida papillifer papillifer, Drawida assamensis, Gordiodrilus elegans, Eutyphoeus assamensis, Eutyphoeus comillahnus and Eutyphoeus gigas) were common to both. While Octochaetona beatrixwas found only in the rubber plantations, Dichogaster affinis was restricted to the mixed forest only. Earthworms were found mostly within 15 cm depth of soils having mean temperature of 27 degrees C, moisture of 23%, pH of 4.57, organic matter of 1.34% and water holding capacity of 36%. Mean earthworm density in rubber plantations (115 ind. m(-2)) was significantly higher (p = 0.003, t = 3.83) than that in the mixed forests (69 ind. m(-2)) due to dominance of Pontoscolex corethrurus, an exotic species. Numbers of dominant species were two (P. corethrurus and D. assamensis) in the rubber plantations and five (P. corethrurus D. assamensis, D. papilliferpapillifer, M. houlleti and Kanchuria sp 1) in the mixed forests. Compared to the mixed forests, significantly low (p<0.05) Shannon diversity index (H) and species evenness and high index of dominance in the rubber plantation were evaluated. PMID- 22319867 TI - Evaluation of drought tolerance of new grapevine rootstock hybrids. AB - The drought tolerance is a very important property of grapevine rootstocks. For that reason the breeding and selection of new rootstock varieties is focused also on the evaluation of their drought tolerance. In this experiment, altogether 20 new hybrids and 4 existing rootstock varieties were compared and evaluated. The experimental scheme involved 3 variants of water supply. Evaluated were the following properties: growth intensity of annual shoots, CCI (chlorophyll content index) and visual characteristics of plants. The most resistant were hybrids from the pedigree groups C (Binova x Borner), D /Binova x/(Binova x Teleki 5C/) x Borner/, and F (Teleki5 Cx Borner). The following hybrids were classified as drought-tolerant: 17-1-6 (C); 17-1-9 (C); 17-6-2 (C); 17-6-9 (C); 17-8-2 (D) and 9-20-1 (F). Based on obtained experimental results and also on correlations existing between individual traits it can be concluded that practically all traits under study may be used when evaluating the resistance of plants to drought. The obtained results indicated that the Borner rootstock (and thus also the species Vitis cinerea) can be used as a suitable genetic resource for the purpose of the breeding grapevine rootstocks for tolerance to drought. PMID- 22319868 TI - Monthly changes in the abundance and biomass of zooplankton and water quality parameters in Kukkarahalli Lake of Mysore, India. AB - Zooplankton abundance and distribution are of ecological importance, as they are very sensitive to change, therefore zooplankton make ideal indicators of aquatic ecosystem. This study carried out on the abundance of rotifer, cladoceran, cyclopoid-copepod and ostracod zooplankton groups and biomass of total zooplankton were studied every month for one year. It is interesting and noteworthy to note that Calanoid and Harpacticoid zooplankton groups and free carbon dioxide were completely absent in all the four sampling sites throughout the study year. About 53% of the variation in the abundance of Cladoceran, 55% of variation in the Cyclopoid-copepod, 39% of variation in the ostracod and 53% of variation in the abundance of total zooplankton were mainly due to pH. Interestingly, negative relationship was found between the total zooplankton and concentration of phosphate as in this lake 67% decrease in wet biomass was mainly because of phosphate, where as 47% of dry biomass of total zooplankton was positively correlated with conductivity. PMID- 22319869 TI - Assessment of genetic variation in lucerne (Medicago sativa L.) using protease inhibitor activities and RAPD markers. AB - The aim of the present study is to identify and characterize lucerne lines resistance to weevil infestation. After three years of field screening for resistance to weevil infestation, 13 lines of lucerne were selected to assess the genotypic variations for lucerne weevil (Hypera postica Gyll.) at biochemical and molecular levels. Total phenols varied from 0.15 to 0.91 mg g (DM) in these genotypes. The highest trypsin (11.11 unit mg(-1) protein) and chymotrypsin (93.0 unit mg(-1) protein) inhibitors activities were recorded in G-1-02 and B-4-03 lines respectively, whereas highest alpha-amylases inhibitor activity (14.2 unit mg(-1) protein) in C-6-01. Zymogram patterns for trypsin inhibitor activity showed quantitative variations among the lines. In total 262 DNA fragments were generated when 45 deca-mer random primers were employed. Genetic variation in terms of genetic distance ranged from 0.65 to 0.85. Sequential Agglomerative Hierarchical and Nested (SAHN) clustering using the Un-weighted Pair Group Method with Arithmetic mean (UPGMA) algorithm yielded two clusters (cluster I and II) which converged at 72% similarity level. Cluster I contained most of the lines having low level of weevil infestation. High bootstrap values (>40) indicated the significance of nodes embodied in these two clusters. However, SDS-PAGE analysis of the leaf proteins of these 13 lines showed no major variations except minor difference in the protein bands of molecular weights between 14 to 20 kD. PMID- 22319870 TI - Influence of invasive plant Coreopsis grandiflora on functional diversity of soil microbial communities. AB - Biological invasions are increasingly attracting the ecologists' attention. Invasive plants threaten the natural ecosystems not only by competing with the native plants, but also by altering the structure and function of soil microbial communities belowground. In this study, we studied the effects of the invasive plant Coreopsis grandiflora (C. grandiflora) on the functional diversity of soil microbial communities in Laoshan mountain in the province of Shandong, North of China. We sampled soil from plots that were invaded or not invaded by C. grandiflora. The functional diversity of microbial communities in the sampled soils was assessed by the Biolog procedure test. By the ANOVA analysis of average well color development (AWCD), Shannon index (H'), Shannon evenness (E), principle components analysis of the level physiological profiles (CLPP) and correlation analysis between the studied parameters, we found that the invasive species C. grandiflora enhanced the functional diversity of soil microbial communities where the habitat was invaded by the C. grandiflora. The study indicated thatthe successful invasive plants have profound effects on the function of soil microbial communities. PMID- 22319871 TI - Effect of pH and salinity on pathogenicity of Flavobacterium columnare and Myxobacterium sp. in Indian cat fish, Clarias batrachus (Linn.) and Heteropneustes fossilis (Bloch.). AB - Flavobacterium columnare (FC) and Myxobacterium sp. recorded persistently associated in fish hatchery and culture system of Himalayan and Sub - Himalayan regions were found to be pathogenic. The pH and salinity played a significant role on the pathogenicity of these potent pathogens in case of Clarias batrachus and Heteropneustes fossilis. LD50 value of FC was 10(4.5) CFU in both the fishes and those of Myxobacterium sp it was 10(6) CFU ml(-1) fish(-1). Fish challenged with F. columnare and Myxobacterium sp. (@ 0.2 ml fish(-1)) individually consisting 10(5-6) cfu ml(-1) exhibited explicit symptoms of columnaris disease and marked with ulceration and saddle back lesion on the dorsal side of body. Maximum reisolation of inoculated bacteria was recorded at pH 7.0 and 7.5 and at 0.0-0.5 (F. columnare) and 0.0-1.0% (Myxobacterium sp.) salinity. Foregoing results elucidated that F. columnare was more sensitive to salinity in comparison to Myxobacterium sp. and their pathogenicity significantly (p<0.05) depends on the salinity and pH that might be one of the physical factors to control their proliferation. PMID- 22319872 TI - Effect of arbuscular mycorrhizal (AM) fungus and plant growth promoting rhizomicroorganisms (PGPR's) on medicinal plant Solanum viarum seedlings. AB - A green house nursery study was conducted to assess the interaction between arbuscular mycorrhizal (AM) fungus, Glomus aggregatum and some plant growth promoting rhizomicrooganisms (PGPR's), Bacillus coagulans and Trichoderma harzianum, in soil and their consequent effect on growth, nutrition and content of secondary metabolities of Solanum viarum seedlings. Triple inoculation of G. aggregatum+B. coagulans+T. harzainum with Solanum viarum in a green house nursery study resulted in maximum plant biomass (plant height 105 cm and plant dry weight 12.17 g), P, Fe, Zn, Cu and Mn and secondary metabolities [total phenols (129.6 microg g(-1) f.wt.), orthodihydroxy phenols (90.6 microg g(-1) f.wt.), flavonoids (3.94 microg g(-1) f.wt.), alkaloids (5.05 microg g(-1) f.wt.), saponins (5.05 microg g(-1) f.wt.) and tannins (0.324 microg g(-1) f.wt.)] of S. viarum seedlings. The mycorrhizal root colonization and spore numbers in the root zone soil of the inoculated plants increased. The enzyme activity namely acid phosphatase (53.44 microg PNP g(-1) soil), alkaline phosphatase (40.95 microg PNP g(-1) soil) and dehydrogenase (475.5 microg PNP g(-1) soil) and total population of B. coagulans (12.5x10(4) g(-1)) and T. harzianum (12.4 x 10(4) g(-1)), in the root zone soil was found high in the triple inoculation with G. aggregatum+B. coagulans+T. harzianum that proved to be the best microbial consortium. PMID- 22319873 TI - Effects of pitamin on growth performance, carcass characteristics and cecal microflora of broiler chicken. AB - The aim of this study is to determine the effect of dietary pitamin as an antibiotic replacement in broiler chicken. The treated groups were as follows: 1) the control, 2) the antibiotics (8 mg of avilamycin kg(-1) of diet) and 3) the pitamin (70 mg of pitamin kg(-1) of diet) groups. Body weight gain, feed intake, and feed efficiency were significantly higher in the pitamin group than in the antibiotics and control groups (p<0.05). Carcass weight, dressing percentage, and the weight of breast and thigh muscle recorded significantly higher levels in the pitamin group as compared to the other groups (p<0.05). The addition of pitamin to the diets for broilers reduced abdominal fat by 23.35% and stimulated the growth of the thymus, the spleen, and the bursa of Fabricius. TAG levels of the pitamin group declined by 12.03 and 10.45% as compared to the control and antibiotics groups, and their TC levels were reduced by 15.17 and 14.39%, and LDL. C levels were reduced by 10.56 and 11.24%, respectively. Serum IgG was increased significantly by 137.43 and 36.80% in the pitamin group as compared to the control and antibiotics groups, respectively (p<0.05). The numbers of Bifidobacterium and Lactobacillus on the cecum digesta were significantly higher in the pitamin group than in the antibiotics and control groups and the numbers of Escherichia coli and Salmonella tended to be reduced (p<0.05). In conclusion, when Korean red pine bark extract, pitamin, was added to the broiler diets at a concentration of 70 mg of pitamin kg(-1) of diet, it resulted in better growth performance as compared to the antibiotics by improving immunity and the cecal beneficial microfloral population. PMID- 22319874 TI - Chromium accumulation in submerged aquatic plants treated with tannery effluent at Kanpur, India. AB - Aquatic macrophytes have been widely studied because of their capability of absorbing contaminants from water and their subsequent use in biomonitoring. This study presents a comparison of Cr accumulating potential of submerged aquatic plants viz Vallisneria spiralis and Hydrilla verticillata. These plants were treated with various concentrations of treated tannery effluent collected from UASB, Jajmau, Kanpur under repeated exposure in controlled laboratory conditions in order to assess their maximum bioaccumulation potential. The maximum accumulation of 385.6 and 201.6 microg g(-1) dry weight was found in roots of V. spiralis and the whole plants of H. verticillata, respectively at 100% concentration after 9th day of effluent exposure. The chlorophyll and protein content of both species decreased with increase in effluent concentration and duration. At highest concentration and duration a maximum reduction of 67.4 and 62.66% in total chlorophyll content, 9.97 and 4.66% in carotenoid content and 62.66 and 59.36% in protein content was found in V. spiralis and H. verticillata respectively. Anatomical studies in both V. spiralis and H. verticillata was carried out to assess the effects of metal accumulation within the plants. Changes in the anatomical structures of both plants exhibits the capacity of these species to act as indicator of effluent toxicity. The high accumulation potential of Cr by both plants revealed their capability to remove pollutants from effluent. PMID- 22319875 TI - Population dynamics of earthworms in relation to soil physico-chemical parameters in agroforestry systems of Mizoram, India. AB - Earthworm population dynamics was studied in two agroforestry systems in the tropical hilly terrain of Mizoram, north-east India, over a period of 24 months, from July 2002 to June 2004. Two sites of agroforestry situated at Sakawrtuichhun (SKT) and Pachhunga University College (PUC) campus, Aizawl, having pineapple as the main crop, were selected for detail studies on population dynamics. Five of the total twelve species of earthworm reported from the state were recorded in the study sites. The density of earthworm ranged from 6 to 243 ind.m(-2) and biomass from 3.2 - 677.64 g.m(-2) in SKT. Comparatively the density and biomass in PUC, which is at relatively higher altitude were lowerwith a range of 0 to 176 ind.m(-2) and biomass from 0 - 391.36 g.m(-2) respectively. Population dynamics of earthworm was significantly correlated with rainfall and physical characters of the soil. Earthworm biomass was significantly affected by rainfall and moisture content of the soil. The influence of chemical factors was relatively less. PMID- 22319876 TI - Role of phosphate solubilizing bacteria on rock phosphate solubility and growth of aerobic rice. AB - Use of phosphate-solubilizing bacteria (PSB) as inoculants has concurrently increased phosphorous uptake in plants and improved yields in several crop species. The ability of PSB to improve growth of aerobic rice (Oryza sativa L.) through enhanced phosphorus (P) uptake from Christmas island rock phosphate (RP) was studied in glasshouse experiments. Two isolated PSB strains; Bacillus spp. PSB9 and PSB16, were evaluated with RP treatments at 0, 30 and 60 kg ha(-1). Surface sterilized seeds of aerobic rice were planted in plastic pots containing 3 kg soil and the effect of treatments incorporated at planting were observed over 60 days of growth. The isolated PSB strains (PSB9 and PSB16) solubilized significantly high amounts of P (20.05-24.08 mg kg(-1)) compared to non inoculated (19-23.10 mg kg(-1)) treatments. Significantly higher P solubilization (24.08 mg kg(-1)) and plant P uptake (5.31 mg plant(-1)) was observed with the PSB16 strain at the highest P level of 60 kg ha(-1). The higher amounts of soluble P in the soil solution increased P uptake in plants and resulted in higher plant biomass (21.48 g plant(-1)). PSB strains also increased plant height (80 cm) and improved root morphology in aerobic rice. The results showed that inoculation of aerobic rice with PSB improved phosphate solubilizing activity of incorporated RP. PMID- 22319877 TI - Effect of phosphogypsum amendment on soil physico-chemical properties, microbial load and enzyme activities. AB - Phosphogypsum (PG) is produced as a solid waste from phosphatic fertilizer plants. The waste slurry is disposed off in settling ponds or in heaps. This solid waste is now increasingly being used as a calcium supplement in agriculture. This study reports the effectof PG amendmenton soil physico chemical properties, bacterial and fungal count and activities of soil enzymes such as invertase, cellulase and amylase over an incubation period of 28 days. The highest mean percent carbon loss (55.98%) was recorded in 15% PG amended soil followed by (55.28%) in 10% PG amended soil and the minimum (1.68%) in control soil. The highest number of bacterial colonies (47.4 CFU g(-1) soil), fungal count (17.8 CFU g(-1) soil), highest amylase activity (38.4 microg g(-1) soil hr( 1)) and cellulase activity (38.37 microg g(-1) soil hr(-1)) were recorded in 10% amended soil. Statistically significant difference (p<0.05) has been recorded in the activities of amylase and cellulase over the period of incubation irrespective of amendments. Considering the bacterial and fungal growth and the activities of the three soil enzymes in the control and amended sets, it appears that 10% PG amendment is optimal for microbial growth and soil enzyme activities. PMID- 22319878 TI - Organic matrix based slow release fertilizer enhances plant growth, nitrate assimilation and seed yield of Indian mustard (Brassica juncea L.). AB - Field experiments were conducted to study the effect of organic matrix based slow release fertilizers (SRFs) on plant growth, nitrate assimilation and seed yield of Brassica juncea L. cv, pusa bold. The agro-waste materials like cow dung, clay soil, neem leaves and rice bran were mixed together in 2:2:1:1 ratio and used as organic matrix for the immobilization of chemical fertilizer nutrients with commercial grade saresh (Acacia gum, 15% solution) as binder. Different fertilizer treatments were organic matrix based slow release fertilizers, SRF-I (542.0 kg ha(-1)); SRF-II (736.5 kg ha(-1)) and chemical fertilizer combinations, boron (3 kg ha(-1))+sulphur (15 kg ha(-1))+nitrogen (80 kg ha(-1)) and boron (3 kg ha(-1)) + sulphur (15 kg ha(-1))+nitrogen (80 kg ha(-1))+phosphorus (15 kg ha( 1))+potassium (100 kg ha(-1)). Organic matrix based SRF-II released ammonium up to 50-d in wetsoil under laboratory conditions which showed maximum retention of the nutrients. Avery significant increase in plant growth, nitrate assimilation and seed yield was recorded in organic matrix based SRF-II applied plants. The maximum percent increase in biomass production was observed with organic matrix based SRF-II (increase of 65.8% in root fresh weight, 38.0% in root dry weight, 45.9% in leaf fresh weight plant(-1) and 27.5 % in leaf dry weight plant(-1) in 60-d old plants). It also increased the acquisition and assimilation of nitrate from the plant's rhizosphere which was evident by 45.6% increase in nitrate, 27.5% in nitrite and 11.7% in nitrate reductase activity (NRA) in leaves of 45-d old plants over control. The organic matrix based SRF-II significantly increased the seed yield by 28% in Indian mustard. Cost analysis revealed thatthis formulation is cost effective as it is based on agro waste materials. PMID- 22319879 TI - Influence of the local spring warming on the breeding phenology in blackcap (Sylvia atricapilla) in Croatia. AB - Recent papers have shown that climate change affects many species, including birds. Several papers from different areas have devoted attention to the negative correlation between the dates of breeding and year, and also negative correlation between the dates of breeding and air spring temperatures. Recent work give some firm evidence for postulating causal relationship between spring temperature and laying dates. We used 31 years (1979-2009) of data from blackcap Sylvia atricapilla in Mokrice area, Northwestern Croatia to assess whether there has been any systematic change in breeding phenology through time.Among environmental factors possibly affecting the breeding date, consideration was given to mean monthly air temperatures (April-May). Over the past three decades, the breeding date of blackcap in our study population has changed significantly: They started breeding progressively earlier (11.77 days). Two regression analysis with laying date as criterion variable showed that spring temperatures can significantly predict variation of laying date and that there are also some other unknown factors which significantly explain variation of laying date. We conclude that blackcaps across Northwestern Croatia are breeding earlier and that mean air spring temperatures is probably the most important factor causing it, among other factors. PMID- 22319880 TI - Effect of varying pH on protein composition and yield of amaranth seed (Amaranthus blitum). AB - The isolation procedure of the seed proteins of Amaranthus blitum have been analyzed at different pH conditions. Qualitative studies were carried out by using electrophoretic technique sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Mainly four protein fractions i.e. albumin, globulin, prolamin and glutelin were obtained. Protein isolates were prepared by (a) extraction at different alkaline pH (9, 10, 11 and 12) and precipitation atpH 5 and (b) extraction at pH 9 and precipitation atdifferentpH (4, 5, 6 and 7). The composition of isolates, prepared by method (a), depended on extraction pH. The isolate extracted at pH 8 was mainly composed of albumin and globulin, whereas at pH 9, 10 and 11 showed the presence of prolamin and glutelin. Electrophoretic pattern of different isolates had five major bands with molecular weight of 30, 45, 72, 84 and 90 kDt respectively. The increase of the extraction pH led to the increase in protein yield. With method (b) isolates obtained were variable in composition. At pH 7 albumin and prolamine were present, whereas at pH 4, 5 and 6 all 4 protein fractions were precipitated. According to the quantitative estimation of the albumin, globulin, prolamin and glutelin in the seed flour the contents were 26.4, 25, 5.81 and 42.7%, respectively. The results suggest that composition of protein isolates could be controlled by different extraction and precipitation pH. PMID- 22319881 TI - Studies on the reproductive biology of spiny eel, Macrognathus aral from upper Assam. AB - The one-stripe spiny eel, Macrognathus aral (Bloch and Schneider), has been gaining importance not only as a food fish but also as an aquarium fish for its body shape and behaviour. The overall M:F ratio recorded 1:0.27, both the males and females were mostly mature in May-August. The peak values of gonado somatic ratio (GSR) attained during May for males (1.3) and August forfemales (12.4) indicating that the fish have only one breeding season during summer. The range of ova diameter was found to vary from 0.3 to 1.4 mm, the absolute fecundity ranged from 250 (21.6 cm/27.4 g) to 5220.1 (27.2 cm/66.3 g) while relative fecundity ranged from 9.1 to 128.9. The 50% maturity is attained in length group of 10.1-14 cm for males and 14.1-18 cm for females. The species is a moderately fecund, isochronal spawner and having a restricted breeding season. The relationship between fecundity and body weight and length has also been discussed. PMID- 22319882 TI - Analysis of water quality factors influencing the speciation of inorganic nitrogen using GRA. AB - Based on the water quality data from 2006 to 2008, grey relational analysis (GRA) is used to analyze factors that may have influence on the speciation of inorganic nitrogen in the Chengdu section of middle Min river. The results show that water temperature, changing from 20.2 +/- 2.7, 13.4 +/- 5.7 and 16.8 +/- 5.6 degrees C, is the first restrictive factor for the speciation of inorganic nitrogen; it is negatively correlated with the ratio of total ammonia nitrogen to total inorganic nitrogen contents [m(AN)/m(TIN)] in three different periods of wet season, dry season and year-round. The average pH values for years, in wet and dry periods are 7.6 +/- 0.4, 7.3 +/- 0.3 and 7.8 +/- 0.2, respectively, and have different influences in different seasons. It is the second restrictive factor and positive correlation between pH and m(AN)/m(TIN) in wet season and through the year yet it is the fourth factor in dry seasons. The values of dissolved oxygen (DO), which are 4.6 +/- 1.4, 4.6 +/- 2.4, 4.6 +/- 2.0 respectively, is the third factor and negatively correlates with m(AN)/m(TIN) in third different periods. The chemical oxygen demand (COD) indirectly inhibits the nitrifying bacteria because the DO is depleted in the decomposition of organic matter by heterotrophic bacteria, showing the positive correlation.As the alkalinity can meet the requirement of nitrification in wet season and through the year, it is not restrictive factor. However, it is the second restrictive factor in dry season because of low content of alkalinity inhibiting the growth of nitrifying bacteria. PMID- 22319883 TI - Irrigation with domestic wastewater: responses on growth and yield of ladyfinger Abelmoschus esculentus and on soil nutrients. AB - Domestic wastewater is generated continuously and in large quantities. It can serve as an alternative water nutrient source for irrigation. In the present study Abelmoschus esculentus L. (Ladyfinger) was irrigated using untreated wastewater (T1), treated wastewater (T2) and rainwater (T3) in pot experiments. The effect was seen on nutrient fortication, growth and yield of the plant and the nutrient status of the soil. Additionally the build up of Cr, Cu and Zn from the irrigation water were anlayzed in different parts of the plant biomass and in the soil. The sapling survival rate was found to be 87% in T1 followed by T2 and T3. Root shoot ratio under different treatments was found in the order T3 (0.46) >T2 (0.35) >T1 (0.31). The chlorophyll a, b and carotene content in the leaves (mg g(-1)) was found to be 6.3, 0.5, 0.9 under T1, 4.8, 0.4, 0.8 under T2 and 3.2, 0.3, 0.5 under T3 respectively and all the three varied in the order T1>T2>T3. The same trend was found in case of total dry matter (g) T1 (6.3) >T2 (3.7) >T3 (2.3) at p < or = 0.05. There was a considerable increase in nutrients in the soil under T1 and T2 as compared to T3 after final harvest. The organic matter (%), NO3-N and PO4(3-) (mg kg(-1)) content post harvest soil was found to be 3.4, 71, 90 under T1 and 2.9, 52, 63 under T2 respectively. Also, there was an increase in cations Na, K, Ca and Mg in the soil irrigated with T1 and T2 after the final harvest. Thus irrigation with wastewater generally increased soil fertility. Only a small percentage of the heavy metal was bioaccumulated by the plant parts from the irrigation water. There was hardly any metal accumulation in fruits. Bulk of the metal ions remained in the soil. PMID- 22319884 TI - Active pharmaceutical ingredient (api) from an estuarine fungus, Microdochium nivale (Fr.). AB - Various marine habitats sustain variety of bio-sources of ecological and biotech potentials. Pharmaceutical potential compound Cyclosporine A was reported from marine fungus Microdochium nivale associated with Porteresia coarctata, a marine salt marsh grass from mangrove environment distributed along the Central West Coast (CWC) of India. This study involves association of M. nivale with P. coarctata plant, fermentation conditions, purification of Cyclosporine A, chemical characterization etc. Its antifungal inhibition and MIC (Minimum inhibitory concentration) against Aspergillus strains (A. niger, A. japonicus, A. fresenii), yeasts and dermatophytes (Candida sp., Cryptococcus neoformans, Trichophyton mentagrophytes, T. tonsurans, T. violaceum, Microsporium gypsum and Fusarium sp.) were evaluated. However, the MIC against A. japonicus, C. neoformans, Candida sp. and T. tonsurans were confirmed to be as low as 12.5-25 mg disc(-1). The antifungal properties of Cyclosporine A against Aspergillus species, yeast and dermatophytes revealed that CyclosporineAwould be a potential compound for life threatening diseases caused by above fungi in both human and animals. Furthermore, we have reported herewith another source of Cyclosporin Aderived from filamentous fungus, M. nivale. occurring in marine environment. PMID- 22319885 TI - Influence of lead on growth and nutrient accumulation in canola (Brassica napus L.) cultivars. AB - Canola (Brassica napus L.) is commonly used as a hyper-accumulator for phytoextraction of heavy metals from soil and water. Like many other heavy metals, lead (Pb) contaminates soil, water and air and thus it is a great problem. This study was conducted to investigate toxic effects of Pb on growth and nutrient uptake in four canola cultivars. Each of four cultivars of canola (Con-II, Con-III, Legend and Shiralee) was subjected to four levels of Pb (0, 30, 60 and 90 mg Pb kg(-1) of soil) from lead chloride [PbCl2]. Due to Pb toxicity, plant growth was adversely affected and relatively a severe reduction in root biomass (45.7%) was recorded. The Pb accumulation increased both in shoot and root, the highest being in root. The uptake of different nutrients, i.e., N, P, K, Ca, Mg, Zn, Cu and Mn was reduced (38.4, 32.8, 33.1, 49.6, 7.78, 52.0, 42.6 and 45.9%, respectively) in the shoots and that of N, Fe, Zn, and Cu in the roots (48.5, 33.2, 24.3 and 44.8%, respectively) of all canola cultivars. The root K, P, Zn and Mn and shoot P, Mg and Fe contents were less affected, the concentration of Pb, Ca and Mg in roots of all cultivars. Among canola cultivars Con-II and Con-III performed better than Legend and Shiralee in terms of growth (26.03%) and nutrient accumulation. Overall, plant growth and nutrient accumulation in the canola cultivars was hampered due to the presence of Pb. PMID- 22319886 TI - Causes of salinity and plant manifestations to salt stress: a review. AB - Salinity in agricultutal terms is the excess of salts above the level plant require. Most often it poses constrains in the growth hence productivity of the category of plants called glycophytes, wherein falls major crops, therefore is a serious concern. It is often recognized as excess of sodium ions (sodicity) that imparts life threatening consequences in plant due to mal-textured soil hindered porosity and aeration leads to physiological water deficit. Mingling with other edaphic/environmental factors viz. precipitation, temperature, flooding, soil profile, water table exaggerates the catastrophe synergistically. Improper irrigations system, leaching fraction added with land clearing and deforestation have been marked as the major cause. The present review underlines the different sources of salinity stress and their physiological manifestations, toxicity responses alongwith tolerance in plants and management strategies in affected landscapes. PMID- 22319887 TI - Awareness of the mother regarding child abuse and neglect. PMID- 22319888 TI - Evaluating the growth performance in 0-5 years slum children. PMID- 22319889 TI - The story of a poacher-turned-gamekeeper: a twist in animal evolution. PMID- 22319890 TI - Effects of vincristine on the bile flow in male albino rats. AB - Bile secretion is an important function served by the liver. The microtubular system integrity plays a key role in hepatic transport and excretion of several of bile constituents including phospholipids & cholesterol as well as detoxified xenobiotics. Furthermore, an alteration in bile secretion has been proposed as an important cause of enteritis, also a complication of microtubular inhibitors like Vincristine (VCR) that may occur following treatment as an anti cancer drug. The study aims to study the effects of microtubule inhibitor VCR on bile flow and bile composition in rats. For this purpose, male albino rats were studied. One group of five rats was infused with single IV dose of VCR (@1 mg/kg and the other received equal volume of IV vehicular fluid. For bile samples, animals were cannulated, bile flow examined at different time intervals before and after drug administration. Biliary composition studied at second hour post i/v administration. Single dose VCR treatment showed significant rise in the baseline excretion of bile in animals studied during first 2 hrs, although, there was a mild reduction in the biliary flow rate after few hours. Biliary total cholesterol was decreased and cation concentrations increased significantly in the second hour post VCR. The results indicate that the exposure of rats to VCR induces early alterations in biliary secretion. This study may prove useful for the purpose of understanding enteritis in patients undergoing chemotherapy. PMID- 22319891 TI - Myocardial performance in asymptomatic essential hypertension. AB - Prevalence, determinants, and prognostic value of left ventricular function in subjects with asymptomatic essential hypertension are still incompletely known. The goal of this study was to investigate the effects of asymptomatic untreated essential hypertension on left ventricular structure and function. The left ventricular functions were assessed among 127 hypertensive and 80 healthy subjects. American society of echocardiography (ASE) convention was applied to measure the stroke volume, percentage ejection fraction, percentage fractional fiber shortening, cardiac output and cardiac index. The stroke volume, cardiac output and cardiac index were normal but significantly high among hypertensive compared to normotensive subjects (P<0.05). The percentage ejection fraction and fractional fiber shortening were significantly reduced among hypertensives compared to normotensives (P<0.05). The significant impairment of percentage fractional fiber shortening is due to alteration in dimension of left ventricular wall thickness, left ventricular cavity and left ventricular geometry. This carries prognostic implication and requires further documentations, investigations and researches. Percentage ejection fraction and fractional fiber shortening is considered a hallmark of normal left ventricular function. The left ventricular contractile state was negatively correlated to left ventricular after load parameters. So the main objective of management of hypertensive subjects should be, to reduce the after load to improve the left ventricular contractile state. PMID- 22319892 TI - Pattern and prevalence of cardiovascular autonomic neuropathy in diabetics visiting a tertiary care referral center in India. AB - The cardiovascular autonomic neuropathy (CAN) is a known complication of long standing diabetes. In the present study, the prevalence of sympathetic and parasympathetic abnormalities in diabetic patients was evaluated on retrospective analysis of standard tests done for the assessment of CAN. Three different scoring systems were utilized for assessment of CAN namely, Ewing's crtieria, Bellavere's criteria and the criteria followed at the Autonomic Function Test laboratory. All the three criteria use different set of tests for classification. A total of 124 patients' laboratory data was analysed. The abnormality of single test ranged from 6.49% in Valsalva Maneuver to 47.41% in cold pressor test. When Bellavere's criteria was used only 53 patients had evidence of CAN while Ewing's criteria revealed that 100 patients had CAN however 69 of these patients could not be categorized. The criteria used by AFT laboratory revealed that isolated sympathetic (49 patients) and paraysmpathetic (10 patients) abnormality can be seen in CAN along with those with combined deficits (42 patients). If the Bellavere's criteria is used then patients with dominant sympathetic neuropathy are likely to be missed during testing. High prevalence of CAN in tertiary care referral centre suggests that the testing of autonomic functions in diabetics should be done routinely. It is recommended that full battery of test to evaluate both the arms of autonomic drive namely sympathetic and parasympathetic should be done and reported as such. PMID- 22319893 TI - Association of albumin-globulin ratio with sympathovagal imbalance in pregnancy induced hypertension. AB - The early prediction of pregnancy-induced hypertension (PIH) is based on the demonstration of increased sympathetic activity in early part of pregnancy. However, the mechanisms that increase sympathetic activity in PIH have not yet been fully elucidated. Therefore, in the present study we have investigated the link of albumin-globulin ratio (AGR) to sympathovagal imbalance in PIH patients. Spectral analysis of HRV was performed in three groups of subjects (Group I: normal pregnant women; Group II: pregnant women with risk factors for PIH, but did not develop PIH; Group III: pregnant women with risk factors and developed PIH) and their biochemical parameters including AGR were recorded. It was observed that LF-HF ratio, the most sensitive indicator of sympathovagal balance was significantly high (P < 0.01) since early pregnancy in group III compared to other groups, which was considerably correlated with AGR in group III (PIH subjects). It was suggested that alteration in AGR could have direct contribution to the sympathovagal imbalance that plays a critical role in the genesis of PIH. PMID- 22319894 TI - Effect of extended colostrum feeding on the plasma profile of insulin, thyroid hormones and blood glucose of crossbred pre-ruminant calves. AB - In the present study, the effect of extended colostrum feeding on certain physiological and endocrinological parameters of pre-ruminant crossbred calves from birth to one month of age was investigated. Estimation of blood glucose level, plasma concentration of anabolic hormones as thyroid hormones and insulin were performed and compared with control calves (G-I) which were fed with colostrum for the first three days of age and thereafter with the whole milk, till 30 days of age. There was steady increase in the blood glucose level (BGL) from birth to one month of age in both groups of calves, with the rise being slightly higher in the calves of G-II group, which is attributed to the action of glucagon by gluconeogenesis especially in the neonates. Intake and absorption of increased amounts of dietary proteins and amino acids in colostrum stimulated a significant increase in the plasma insulin concentration in G-II calves compared to G-I calves, over and above the accelerated tissue development of pancreas. Fluctuating levels of thyroid hormones in plasma of calves of both the groups suggested that the concentration of thyroid hormones were not influenced either by extended colostrum or whole milk feeding in calves, but rather followed a diurnal rhythm. PMID- 22319895 TI - Effect of gender on the association of adiposity with cardiovascular reactivity in Gujarati Indian adolescents. AB - Studies have reported that both gender and adiposity influence cardiovascular reactivity amongst adolescents. However, not much is known about the effect of gender on the association of adiposity with cardiovascular reactivity. The current study was conducted to learn how gender affects the association of adiposity with cardiovascular reactivity in the Gujarati Indian adolescents so as to develop preventive strategies for the local population. A cross-sectional study was conducted on 428 (Girls-173, Boys-255) Gujarati Indian adolescents of age group 16-19 years. Adiposity was assessed in terms of Body Mass Index (BMI), Body Fat Percentage (BF %), Fat Mass (FM), Fat Mass Index (FMI) and Waist Circumference (WC). Percentage Rise in Pulse Rate (%RPR) and Percentage Rise in Diastolic Blood Pressure (%RDBP) during Isometric Handgrip Test were used to assess the cardiovascular reactivity to acute sympathetic stress. Pearson's correlation coefficient was determined to find the association of adiposity with cardiovascular reactivity. Boys were found to have a significantly larger WC, higher physical fitness and greater %RDBP in comparison to girls while girls had a significantly higher BF% and FMI in comparison to boys. In both boys and girls, BMI, BF%, FMI and WC showed significant positive association with %RDBP with stronger correlationship found in girls. Girls also showed a significant negative correlationship between physical fitness and vascular reactivity. It could thus be concluded that gender affected the association of adiposity with vascular reactivity in Gujarati Indian adolescent such that girls tend to have a larger correlationship between adiposity and vascular reactivity than boys which is most likely due to lower physical fitness. PMID- 22319896 TI - Acute effects of deep breathing for a short duration (2-10 minutes) on pulmonary functions in healthy young volunteers. AB - Breathing is the most vital function for maintenance of life. Slow and deep breathing is an integral part of Pranayama and it reduces dead space ventilation and renews air throughout the lungs. The reported beneficial effects of deep breathing as a part of either long term or short term practice of Pranayama are well documented. However our knowledge about the effects of a few minutes' of deep breathing on human ventilatory parameters is poor. In the present study, we examined the relationship between exposure to short duration of deep breathing and performance on pulmonary function tests before and after the deep breathing. The study was conducted in a homogenous group of 12 volunteers containing 4 females and 8 males who were well trained in pulmonary function testing (PFT) before the start of the study. The volunteers performed deep breathing (DB) exercise for 2, 5 and 10 minutes at the rate of 6 breaths per minute under guidance, and the duration of DB exercise for that day was randomly selected for each group. PFT was done before and after the DB exercise. There was a significant (P < 0.05) increase in vital capacity (VC) after 2 and 5 minutes' DB exercise and a consistent improvement in tidal volume (TV) and minute ventilation (MV) after the DB exercise in all the three groups, though it wasn't statistically significant. There was a significant (P < 0.05) increase in forced vital capacity (FVC) after 2 minutes' of DB exercise and a consistent increase in all the three groups in forced inspiratory vital capacity (FIVC) and peak inspiratory flow rate (PIFR), though this increase was not statistically significant. This shows that deep breathing exercise, even for a few minutes' duration is beneficial for the lung functions. PMID- 22319897 TI - Study of short term memory status in adult bipolar disorder patients in south Indian population. AB - The present study was undertaken to establish short term memory status in bipolar disorder cases as compared with normal age and sex matched control group in Bijapur (Karnataka). Results showed that a significant decrease in short term memory status in bipolar disorder cases as compared to their control group .Loss of attention, decreased processing speed and executive function patterns may be the probable causes of such observations. PMID- 22319898 TI - Effect of different phases of menstrual cycle on physical working capacity in Indian population. AB - Women in large number are engaged in skilled and unskilled sectors of job and there is increasing participation of women in sports, Considering the fact that cyclical endocrine profile in females can have bearing on cardiovascular and respiratory function, in turn on physical capacity, The study of effects of phases of menstrual cycle on physical working capacity was undertaken in 40 female students of Bangalore Medical College. The subjects were instructed to come to the lab during each of three different phases of menstrual cycle. Resting heart rate (HR), respiratory rate (RR), BP were recorded. Subjects were made to exercise on Bicycle Ergometer and their maximum aerobic capacity was assessed as PWC170 (Physical working capacity at the heart rate 170). On statistical analysis we found resting RR and resting HR high during luteal phase with 'P' values of P < 0.01, P < 0.01 respectively. We also found PWC170 decreased during luteal and menstrual phase with 'P' values of P < 0.05 and P < 0.01. From the present study it can be concluded that resting HR and RR are increased during the luteal phase. Also PWC170 is decreased during the luteal and menstrual phases, this can have an adverse effect on the physical work output of females during these two phases. PMID- 22319899 TI - Reduction in lung functions in type-2 diabetes in Indian population: correlation with glycemic status. AB - The purpose of this study was to evaluate pulmonary functions in patients with Type-2 diabetes mellitus and to determine their correlation with glycemic status of diabetes in Indian population. Forty Type-2 diabetic patients, aged 30-60 years, with diabetic duration of 1-20 years, were included in the study. FVC, FEV1, & FEV1% are recorded by Benedict's Roth spirometer. PEFR and MEP were recorded by Wright's Peak flow meter & Modified Black's apparatus. Glycemic status of subjects was determined by FBS & PPBS by Glucose oxidase & peroxidase methods. And results were analyzed by calculating Mean +/- SD, using Student's t test, and Pearson correlation. All the respiratory parameters are reduced in Type 2 diabetic patients compared to control of which FEV1, FEV1%, & MEP show very highly significant reduction (P=0.000). Lung functions are negatively correlated with glycemic status & duration of diabetes. (r = -0.390, & -0.342) Reduction in dynamic lung functions and its negative correlation to glycemic status might be due to respiratory muscle weakness as indicated by highly significant reduction in MEP. Hence strict glycemic control and breathing exercises to strengthen the respiratory muscles may improve lung function in diabetics. PMID- 22319900 TI - Effect of methylphenidate on enhancement of spatial learning by novel alternated dual task. AB - The novel alternated dual task (ADT) arranged rats to learn T-maze spontaneous alternation task and radial arm maze (RAM) task alternatively, and by doing ADT, rats could acquire the tasks more easily than non alternated dual task (NADT) group. Also retention capacity of ADT group was significantly more and ADT help to learn a complex task faster than learning it in isolation from other tasks. In the present study effect of methylphenidate (MPD), a mood elevator, known to enhance learning and memory, on ADT procedure is assessed. Also effect of ADT procedure and MPD on spatial learning and memory are compared. Different groups were assigned by administering MPD (intraperitoneal injection at a dose of 3 mg/kg body weight) during different phases of behavioural experiments, and control groups received saline injection. MPD administration increased both acquisition and retention capacities. The amelioration attained for retention of complex task by ADT procedure, could be achieved by NADT rats only by administration of MPD. The influence of ADT procedure on acquisition and retention of TM and RAM tasks were similar to the effects of MPD, especially for the RAM task. MPD at low dose is found to enhance the learning and memory capacity in rats, than deteriorating it, supporting the use of MPD as a drug to treat attention deficit hyperactive disorder. The recent reports suggesting the effect of MPD only on retention and not on acquisition could not be confirmed, as enhancement for both acquisition and retention was found in this study. PMID- 22319901 TI - The effects of Sudarshan Kriya Yoga on some physiological and biochemical parameters in mild hypertensive patients. AB - An open label intervention study was undertaken on 26 mild hypertensives and 26 apparently healthy adults (30-60 y), for the effect of Sudarshan Kriya Yoga practice for two months as complementary therapy. In the hypertensives, there was a significant decrease in diastolic blood pressure (P < 0.01), serum urea (P < 0.01) and plasma MDA (malondialdehyde adducts) as oxidative stress marker (P < 0.05). Other parameters; viz.; plasma levels of cholesterol, triglycerides, glucose, did not change significantly (P > 0.1). The pattern of change in most of the study parameters was such that values above normal range were lowered but values within normal range were unaltered. The action of Yoga on diastolic blood pressure, malondialdehyde adducts and kidney function in hypertensives was of counteractive nature and felt to be distinctly different than the effect of drugs. PMID- 22319902 TI - Comparison of VO2max in obese and non-obese young Indian population. AB - Incidence of obesity in early life is increasing nowadays because of faulty food habits and lack of exercise. This study was aimed to find out whether obesity affects cardiorespiratory efficiency of young adults. As VO2max is the most accepted indicator of cardiorespiratory efficiency it was compared in 30 obese and 30 non-obese subjects aged around 18-20 years. VO2mx was estimated by Queen's college step test. Various other parameters measured and calculated are weight, height, BMI, skin fold thickness, percentage body fat, lean body mass, fat mass. The results showed that cardiorespiratory efficiency (absolute VO2max & VO2max/kg lean body mass) was not affected (P > 0.05) in obese group in both sexes. Ability to do exhausting work (VO2max/kg body weight) was less in obese group (P = 0.001) compared to non-obese group & in obese males (P < 0.01) as compared to non-obese males. Percentage body fat (r = -0.416), triceps skin fold thickness (r = -0.427) and calf skin fold thickness (r = -0.381) strongly correlate to VO2max/kg body weight. Therefore the exercise programs can be best designed to increase caloric expenditure and thus to decrease body fat rather than to improve aerobic fitness. PMID- 22319903 TI - Looking forward. PMID- 22319904 TI - Bariatric surgery studies exemplify the ACS' commitment to inspiring quality. PMID- 22319905 TI - The best time to be a surgeon. PMID- 22319906 TI - When things go wrong. PMID- 22319907 TI - Stress, burnout, and maladaptive coping: strategies for surgeon well-being. AB - Practicing physicians and surgeons, medical and surgical residents, and medical students dedicate their lives to providing optimum patient care, but doing so places them at significant risk for personal and professional stress and, ultimately, burnout. Of great concern is the fact that unrecognized stress and unmanaged burnout are more prevalent among residents than previously believed. Research shows that stress without conflict resolution may lead to burnout, which can contribute to impaired technical performance, medical errors, physical and mental health problems, and even increase the risk of suicide. Therefore, it is crucial that surgeons, and the organizations that train and employ them, recognize the early signs of stress and burnout, adopt adaptive coping strategies, and maintain a culture wherein work-life balance and surgeon well being are shared goals. PMID- 22319908 TI - Financial planning for residents. PMID- 22319909 TI - The psychosocial toll of a surgical career. PMID- 22319910 TI - The future of surgery: autonomy or employment? AB - History has shown that the professions of medicine and surgery have been in constant evolution. Physicians, including the historical barber surgeons, often remained focused only on medical practice and patient care. As a result, the medical profession had a reactionary response to the financial and political circumstances that developed over time. Subsequently, physicians have worked in environments designed by nonphysicians lacking the benefit of medical insight. The most poignant example of this in the U.S. was the rapid development of private insurance and Medicare. Due to the surrounding financial and political forces, these programs rapidly changed the practice environment of medicine. Physicians found that they needed to participate in these programs to remain financially solvent. Various countries around the world have faced similar challenges of increasing health care cost. As populations expand, the need for care increases, but is limited by available resources. These global experiences can lend insight into the effects of different models and how variations may or may not work within the U.S. The effects of those systems demonstrate the importance of physician input into the development of new models. A long-standing unwritten rule in medicine has taught generations of physicians to avoid discussing reimbursement and health care politics. Yet, in order to recruit the brightest minds with a compassionate bedside manner, excellent judgment, and high vigilance toward patient care, medical professionals need to discuss topics related to reimbursement. The government, insurance company administrations, and other lobby interest groups freely express their interests in these issues. Physicians must engage in health care politics to ensure an adequate physician pool in the future to take care of patients. By influencing the structure of the health care system, including physician reimbursement, all patient care can be positively influenced. PMID- 22319911 TI - Do simulator training and duty hour restrictions lead to safer surgery? PMID- 22319912 TI - Who will land the plane in the Hudson? PMID- 22319913 TI - The era of the simulated surgeon. PMID- 22319914 TI - Approaches to maintaining high-quality surgery training in the twenty-first century. PMID- 22319915 TI - It is time for a paradigm shift in surgical training regulation. PMID- 22319916 TI - Volume dictates outcomes. PMID- 22319918 TI - The "write" stuff: an interview with columnist and author Pauline W. Chen, MD, FACS. Interview by Tony Peregrin. PMID- 22319917 TI - External vs. internal motivators: against increasing requirements. PMID- 22319919 TI - ACS state chapter lobby day program. PMID- 22319920 TI - Robust Process Improvement at The Joint Commission. PMID- 22319921 TI - Looking forward. PMID- 22319922 TI - The CY 2012 Medicare physician fee schedule proposed rule. PMID- 22319923 TI - 2011 Executive Director's annual report. PMID- 22319924 TI - A year of inspiring change. PMID- 22319925 TI - Presidential address: Stewardship of our profession. PMID- 22319926 TI - Reflections on early surgical contributions to palliative care. PMID- 22319927 TI - Surgical coding across the spectrum. PMID- 22319928 TI - Medical malpractice reform in North Carolina. PMID- 22319929 TI - SGO releases national agenda for women's cancer research. PMID- 22319930 TI - The 2011 annual report shows improvement in surgical care measures. PMID- 22319931 TI - Looking forward. PMID- 22319932 TI - 2011 state legislative wrap-up. PMID- 22319933 TI - Surgical volunteerism in Vietnam: surgeons and educators strengthen the U.S. Vietnam relationship. PMID- 22319934 TI - Third annual RAS essay contest: My experience with a dying patient. PMID- 22319935 TI - Palliating who? PMID- 22319936 TI - Bond of shared humanity. PMID- 22319937 TI - Choices. PMID- 22319938 TI - Quality of life vs. quantity. PMID- 22319939 TI - Chain of souls. PMID- 22319940 TI - First encounters. PMID- 22319941 TI - Practical hippocrates. PMID- 22319942 TI - A sacred bond. PMID- 22319943 TI - "It's ok". PMID- 22319944 TI - Death is not failure. PMID- 22319945 TI - Sentinel lymph node mapping and its relation to biopsy. PMID- 22319946 TI - Burn care: are there sufficient providers and facilities? PMID- 22319947 TI - State legislatures attempt to shut down the pill mills. PMID- 22319948 TI - TJC's collaboration and partnership with the ACS. PMID- 22319949 TI - [Emotional display rules of Japanese and Koreans]. AB - Hypothetical stories designed to arouse feelings of happiness, sadness, or anger were presented to Japanese (n = 310) and Koreans (n = 286) university students. They were asked to rate the intensity of the emotion experienced, and to select the corresponding facial expression to display in an individual situation and in a social situation. Analyses of covariance were conducted on the rating scores of facial expression using the intensities of emotion as the covariance, except for happiness where the within-class regression coefficients were not homogeneous. The results showed that Japanese and Koreans shared the emotional display rules about the expressions of emotions in individual situations more than in social situations. Japanese thought that they should suppress emotions more than Koreans did. Moreover, the differences in facial expressions between Japanese and Koreans were greater in the individual situations than in the social situations. PMID- 22319950 TI - [Multiple mere exposure effect: category evaluation measured in the Go/No-go association task (GNAT)]. AB - The effect on likability of multiple subliminal exposures to the same person was investigated. Past studies on the mere exposure effect indicated a correlation between the frequency of repeated exposure to the same stimulus and likability. We proposed that exposure to various stimuli of the same person would have a stronger effect on likability. Participants were subliminally exposed to photographs of a person's face taken from seven angles (multi-angle-exposure) three times each (Experiment 1), or photographs of a person with seven facial expressions (multi-expression-exposure) three times each (Experiment 2). Then, the likability toward the exposed person was measured using the Go/No-go Association Task. The results indicated that the effect of the multiple exposures from various angles was equivalent to exposure to only one full-face photograph shown 21 times (Experiment 1). Moreover, likability was significantly higher in the case of exposure to various facial expressions than for exposure to only a single facial expression (Experiment 2). The results suggest that exposure to various stimuli in a category is more effective than repeated exposure to a single stimulus for increasing likability. PMID- 22319951 TI - [Contrast between vowel formants affects impressions of the speaker's personality and speech style]. AB - This study investigated the relationship between the distinctness of vowels in speech and impressions of the speaker's personality and speech style. Vowel sounds are considered to carry mainly phonetic information. For the experiment, formant frequencies of vowel sounds in original speech were altered to synthesize speech stimuli into four levels of formant contrast among different vowels. In Experiment 1, 36 university students listened to the speech stimuli and evaluated the speaker's personality using the Big Five scale. In Experiment 2, 35 participants evaluated the speech style. As the phonetic contrast between vowels became bigger, the trait evaluations of "conscientiousness" showed an asymptotic increase. "Agreeableness" was evaluated as high when the vowel contrast was somewhat bigger than the original before beginning to decrease. Regarding speech styles, "naturalness" and "fluency" were evaluated highest when vowel contrasts were somewhat bigger. "Pleasantness" was evaluated equally high for original and somewhat big contrasts, but lowest for the smallest contrast. In conclusion, vowel distinctness conveys not only phonetic information but also contributes to impressions of speech style and the speaker's personality systematically. PMID- 22319952 TI - [Scheffe-type paired comparison models for examining correlations between individual preferences for alternatives]. AB - It is difficult to estimate and examine correlations between individual preferences for alternatives using the present Scheffe-type paired comparison models. In this paper, we propose two models that address individual preferences for alternatives. One is a simple model that makes it possible to estimate correlations between individual preferences. The other is an improved model that makes it possible to extract independent components from those correlations. Paired comparison data were collected in a survey about preferences for several new product names. Analysis of this data shows that the proposed models enabled the estimation not only of average preferences for alternatives, but also correlations between individual preferences and loading matrices for independent components. The effectiveness of the proposed methods was confirmed by the interpretations of those estimates. PMID- 22319953 TI - [Valences of self-evaluation and approach-avoidance tendencies: research based on regulatory focus theory]. AB - Four studies were conducted to investigate the relationship between valences of self-evaluation and approach-avoidance tendencies. Based on regulatory focus theory (Higgins, 1997, 1998), we predicted that positivity of self-evaluation is related to the tendency to approach gains, while negativity of self-evaluation is related to the tendency to avoid losses. In Study 1, a self-report measure of behavioral tendencies for approaching gains and avoiding losses was developed. In Studies 2 to 4, correlations between these approach/avoidance tendencies and various kinds of self-evaluations were examined. Overall, the authors' predictions were supported. The results suggest that the self-evaluation system and the self-regulation system work in close cooperation with each other in controlling human behavior. PMID- 22319954 TI - [Effect of self-relevance of a non-critical item on physiological responding on the Concealed Information Test]. AB - The effect of self-relevance of a non-critical item in the Concealed Information Test (CIT) was investigated. Respiration, skin conductance response (SCR), heart rate, and normalized pulse volume were recorded while performing the CIT using a stimulus set composed of 4 items (with one self-relevant item). Thirty participants were instructed to recognize one item as critical and the remaining items as non-critical (positive group), and 33 participants were instructed to recognize all items as non-critical (negative group). In the positive group, a differential reactivity was observed between the critical and non-critical items, despite the self-relevance of the non-critical item. In the negative group, a differential reactivity between the self-relevant and non-self-relevant items was observed for SCR only. However, when individual data were analyzed, there was a differential reactivity between self-relevant and non-self-relevant items on physiological measures other than SCR for some participants in the negative group. These results suggest that the self-relevance of a non-critical item might cause false positive results in "negative" participants, particularly when only SCR is used to assess differential reactivity. PMID- 22319955 TI - [The relationship between trust in risk management and anxiety about risk: analyses based on a range of risks]. AB - The present research investigated the relationship between public anxiety about a variety of risks and trust in the management of each risk. Adults (N = 2,200) were selected from the residents' basic registers using a stratified two-step random sampling method. Of this sample, 1,192 (54.2%) rated their anxiety toward 51 kinds of risks and their trust in the management of each risk. Six-point scales were utilized for their ratings. The results demonstrated that the more the risk management was trusted, the less the risk was of concern. The basic statistics for the trust ratings are provided for the discussion of societal risk governance. The implications and limitations of the present findings are discussed. PMID- 22319956 TI - [Facilitating the acquisition of basic counseling skills by modeling and language]. AB - This study investigated the effect of verbalizing a model's performance for the acquisition of counseling skills. Paraphrasing, a counseling skill used in microcounseling, was used as an index of the acquisition of counseling skills. Undergraduate students (N= 56) were randomly assigned to one of the following groups: self-verbalization group (n= 18), experimenter-verbalization group (n = 21), and non-verbalization control group (n = 17). Pretests, posttests, and follow-up tests (one week later) were used to examine paraphrasing scores. Modeling was practiced after the pretest. From the pretest to the posttest, all three groups showed a performance gain, although the self-verbalization group showed a greater performance gain than the other two groups. From the posttest to the follow-up test, the control group showed a performance loss, while the performance of the other two groups remained at the same level. These findings suggest that verbalization of a model's performance in microcounseling improves the acquisition and the maintenance of the counseling skills. PMID- 22319957 TI - The effects of Teucrium polium on ionizing radiation-induced intestinal damage in rats. AB - BACKGROUND AND STUDY AIMS: Oxidative stress plays an important role in development of intestinal injury after abdomino-pelvic radiation therapy. Teucrium polium (TP) is a medicinal plant which has antioxidant and anti inflammatory properties. The aim of this study was to investigate the effect of TP on radiation-induced intestinal oxidative damage in rats. MATERIALS AND METHODS: Group 1 (n = 8), the control group; Group 2 (n = 8), the RAD (radiation) group in which each rat received a single whole-body 800 cGy radiation performed with a LINAC ; Group 3 (n = 8), the RAD + TP group in which rats were exposed to radiation as in Group 2, followed by intragastric administration of 0.5 g/kg/daily TP extract for 7 consecutive days; and Group 4 (n = 8), the TP group, rats received only intragastric TP for 7 days. RESULTS: Radiation led to intestinal damage, which was accompanied by an increase in intestinal thiobarbituric-acid-reactive substances (TBARS) and myeloperoxidase (MPO) levels, and a decrease in reduced glutathione (GSH) levels. Although TP significantly decreased intestinal MPO levels and inflammation scores, it neither reverted intestinal TBARS and GSH levels nor ameliorated other histological parameters of the disease. CONCLUSIONS: Our results suggest that TP reduces inflammation but does not ameliorate the increased oxidative stress conditions in radiation induced intestinal damage in rats. PMID- 22319958 TI - A comparative study between three noninvasive predictors of oesophageal varices in post hepatitis C virus liver cirrhosis in Egypt. AB - BACKGROUND AND AIM: The prevention of variceal bleeding is very important. The current guide lines recommend screening of all cirrhotic patients by endoscopy, to identify patients at risk of bleeding in whom prophylactic treatment should be started. Repeated endoscopic examinations are unpleasant for patients, and carry a high cost impact and burden on endoscopic units, while only 50% of cirrhotic patients have esophageal varices, 30% of whom have large varices. The aim of this study is to evaluate prospectively the spleen size, platelet count and platelet count/spleen diameter ratio as noninvasive predictors of oesophageal varices in post hepatitis C virus liver cirrhosis in Egypt. PATIENTS AND METHODS: One hundred patients with post hepatitis C virus liver cirrhosis were included in the study. All studied subjects underwent a detailed history taking, clinical examination, biochemical workup, upper gastrointestinal endoscopy and abdominal ultrasound. The platelet count to spleen diameter ratio was calculated. RESULTS: All the 3 predictors showed high statistically significant correlation with the presence, size and the grade of oesophageal varices (P < 0.01). Among the 3 noninvasive predictors the platelet count/spleen diameter ratio gave the highest accuracy (94%) at a cut-off value of 1326.58 followed by the spleen size (89%) at a cut-off value of 131.5 mm and lastly the platelet count (84%) at a cut-of value of 131000/mm3. CONCLUSION: The use of the three studied predictors in this study can help the physicians to restrict endoscopy to those who are highly suspected to have oesophageal varices. PMID- 22319959 TI - Risk factors for non-alcoholic fatty liver disease in a Chinese population. AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a serious health concern in China. The goal of this cross-sectional study was to determine the prevalence of NAFLD and identify the risk factors associated with this disease in Northern China. METHODS: In 2007, a total of 6063 adults from Dehui, a city in Northern China, were surveyed and demographic and social-economic characteristics, life behaviors, and medical history were recorded. Among them, 3850 subjects were randomly selected for physical examination, fasting plasma glucose (FPG) test, fasting lipid and liver function profiles, hepatitis B and C infection screening, and ultrasound examination. The frequency of NAFLD in this population was analyzed by the Chi-square test and the association of potential risk factors was analyzed by logistic regression. RESULTS: The prevalence of NAFLD was 15.9% in this population and the prevalence in females was significantly higher than that in males, particularly for the elderly subgroup. Obesity, hypertension, FPG, diabetes, and metabolic syndrome (MS)-related hyperlipidemia were significantly associated with NAFLD. The data indicate that MS-related multiple risk factors synergistically increase the risk for NAFLD. CONCLUSION: The prevalence of NAFLD is high in Northern China, which may be associated with the high incidence of diabetes, hypertension, and MS in this area. PMID- 22319960 TI - Ampulla of Vater tumors: impact of intraductal ultrasound and transpapillary endoscopic biopsies on diagnostic accuracy and therapy. AB - BACKGROUND AND STUDY AIMS: To evaluate the diagnostic impact of intraductal ultrasound (IDUS) and endoscopic transpapillary forceps biopsies (ETP) in ampullary tumors. PATIENTS AND METHODS: Seventy-two patients with suspected ampullary tumor were examined by ERCP, including IDUS and ETP. Histopathological correlation or long-term follow-up was available for all patients undergoing these procedures. Final diagnosis revealed ampullary adenoma in 40 patients and ampullary carcinoma in 32 cases. Sensitivity, specificity, accuracy rates as well as positive and negative predictive values (PPV, NPV) for each of the diagnostic measures were calculated including T and N stage accuracy. RESULTS: Four carcinomas were misclassified by IDUS giving sensitivity, specificity and accuracy rates of 87.5%, 92.5% and 90.2%, respectively. Using ETP a correct pre interventional diagnosis of ampullary carcinoma was achieved in 22 out of 32 patients resulting in a sensitivity, specificity and accuracy data of 68.7%, 100% and 86%, respectively. Improvement of sensitivity and accuracy to 97% and 94.5%, respectively, could be achieved by IDUS in combination with ETP. IDUS accuracy for T1, T2 and T3 stages was 86%, 71% and 86%, respectively. For NO and N1 stages accuracy of 75% each was calculated. CONCLUSIONS: IDUS+ETP substantiate the diagnosis and further management of ampullary tumors. ETP alone is not useful in detecting malignancy (false-negative rate of 31.3%). IDUS accurately predicts T and N stages in patients and is able to accurately predict cases which potentially are treatable endoscopically. PMID- 22319961 TI - Vascular invasion, perineural invasion, and tumour budding: predictors of outcome in colorectal cancer. AB - Tumour stage reflected by the AJCC/UICC TNM system is currently regarded as the most powerful prognostic parameter in patients with colorectal cancer. However, additional histopathological markers are required to improve clinical decision making with respect to follow-up scheduling and administration of adjuvant therapy. In this review we summarize the available literature regarding the prognostic impact of venous and lymphatic invasion, perineural invasion and tumour budding in colorectal cancer. Special emphasis was placed on patients with AJCC/UICC stage II disease, the risk of lymph node metastasis in early cancer and the prediction of local recurrence in rectal cancer. For each of the markers, the different methods of evaluation, implications resulting from different definitions used in previous studies as well as future perspectives are discussed in detail. PMID- 22319962 TI - The role of PET in predicting response to chemotherapy in oesophago-gastric cancer. AB - Treatment options for oesophago-gastric cancers reach from limited resection to multimodality treatment. An accurate clinical assessment and prognostic information are needed for selecting the most appropriate treatment approach. Positron emission tomography (PET) in combination with computed tomography (CT) in a hybrid imaging modality may ameliorate the staging accuracy and add prognostic information. Experiences from specialised centers indicate that PET also may aid to estimate and predict response to preoperative chemotherapy and chemoradiation. This article recapitulates the value of PET in the staging and multidisciplinary care of oesophago-gastric cancer. At this stage, it remains unclear if the prognosis of patients can be improved by implementing PET in the management of this disease. Prospective multicenter studies should be performed to validate metabolic cut-off values and to proof the benefit of PET-guided treatment decisions. PMID- 22319963 TI - Cajal beyond the gut: interstitial cells in the urinary system--towards general regulatory mechanisms of smooth muscle contractility? AB - Interstitial cells of Cajal (ICC), similar to GI pacemakers have been identified throughout the urinary system. Although each part of the system serves a different function, ranging from peristalsis of the ureters, storage of urine by the bladder, and a sphincteric action by the urethra, they share a common mechanism in being able to generate phasic myogenic contractions. Even the urethra, often considered to be a 'tonic' smooth muscle, achieves an apparently sustained contraction by averaging numerous small asynchronous 'phasic' contractions. This activity can occur in the absence of any neural input, implying the presence of an intrinsic pacemaker. Intracellular microelectrode recordings from urethral muscle strips reveal electrical slow waves similar to those of the GI tract. To study this further, we isolated single cells from rabbit urethra and found not only smooth muscle cells (SMC), but a second cell type comprising -10% of the total. The latter cells were branched and non contractile and closely resembled intestinal ICC. Electrophyiological studies revealed that, while the isolated smooth muscle cells were electrically quiescent, the 'ICC' fired electrical slow waves similar to those observed in the whole tissue. The basis of this difference was the presence of a large pacemaker current involving the activation of calcium-activated Cl channels by spontaneous intracellular Ca2+ waves. These, in turn, have been shown to be modulated by neurotransmitters such as nitric oxide, noradrenaline and ATP, thus providing a possible mechanism whereby neural regulation of the urethra, as well as spontaneous tone, may be mediated via ICC. PMID- 22319964 TI - How to prevent post-ERCP pancreatitis? AB - The incidence of post-ERCP pancreatitis (PEP) has remained constant since 30 years. During the last 10 years, large progresses have been made in the knowledge of (i) factors that predispose to PEP and (ii) measures that are effective to prevent PEP. Many of these measures have not yet been widely implemented. Complete recommendations for PEP prophylaxis are summarized in the review. For high-risk ERCPs, including ampullectomy, pancreatic sphincterotomy, precut biliary sphincterotomy, known or suspected sphincter of Oddi dysfunction, pancreatic guidewire-assisted biliary cannulation and endoscopic balloon sphincteroplasty, prophylactic pancreatic stent placement should be considered. For low-risk ERCPs, periprocedure rectal administration of NSAID is recommended. Prophylactic pancreatic stenting should be investigated in terms of education of endoscopists for insertion techniques, ease of stent insertion, reliability of spontaneous stent elimination and safety (demonstration of the absence of induced pancreatic changes). PMID- 22319965 TI - Early versus late immune mediated inflammatory diseases. AB - Immune mediated inflammatory diseases (IMIDs) are life long conditions that cause substantial morbidity and disability. Though increasingly common and intensely studied, the cellular and molecular mechanisms underlying their pathogenesis are still unclear. Despite this incomplete knowledge, it is becoming increasingly evident that IMIDs evolve over time, not only from a clinical perspective but also a pathophysiological one. Evidence is accumulating that the events responsible for inflammation and damage in the target organs are not necessarily the same during the evolution of the IMID, and that the immune response evolves in parallel with the clinical manifestations. This has crucial implications for therapy because immunomodulatory interventions aimed at early pathogenic events may no longer be effective when these events have changed due to a different composition of the immune response. Therefore, it is crucial to better understand why and how the IMID associated immune abnormalities evolve over time, so that time-dependent therapies may be rationally implemented for an improved clinical outcome. PMID- 22319966 TI - Transjugular intrahepatic portosystemic shunt--current status in 2011. AB - This article overviews principles of portal hypertension and the role of implantation of a transjugular intrahepatic postosystemic shunt (TIPS) in its management. Since TIPS is available for over 30 years, technical achievements have been made and knowledge about indications, contraindications and patient selection has been improved. Recent studies and guidelines may lead to an increase in TIPS implantation rates. This review aims to commemorate the merits and demerits of TIPS in current clinical practice. PMID- 22319967 TI - Solid pseudopapillary tumor of the pancreas in a pregnant woman. AB - Solid pseudopapillary tumor (SPT) of the pancreas is a rare neoplasm of low malignant potential that mostly affects young women in the second or third decade of life. The number of such patients reported in the literature has increased in recent years, while SPT in pregnancy is extremely rare. To the best of our knowledge, only one case of SPT in pregnancy has been reported in the English language literature. We herein report a case of asymptomatic SPT in a 26-year-old Chinese female in the 14th week of pregnancy, and present our experience of the surgical management of SPT in pregnancy. PMID- 22319968 TI - Mechanical ileus caused by a tablet of tralgit SR 100 stuck in a stenotic rectum affected by carcinoma: case report and literature survey. AB - A patient with an advanced carcinoma in the recto-sigmoideum was taken for urgent operation because of abdominal pain, significant distension of colon, clinical symptoms and radiological proofs of ileus. The cause of the complete obstruction of the proximal rectum which was significantly narrowed by a tumour was one tablet of Tralgit SR 100, which had been administered to the patient for 4 weeks after osteosynthesis of the right femur neck following fracture. According to the radiologist between 45 and 50 tablets of the medicament had been found in the digestive tract. The mechanical ileus was solved by operation according to Hartmann. This case has two aspects: 1) surgical--mechanical ileus resulting from a rare set of circumstances, and 2) pharmacological and metabolic--disorder of medicament absorption in the digestive tract. The cause of maldigestion (disorder of absorption) of the Tralgit tablets is further investigated. PMID- 22319969 TI - Delayed liver metastasis of a meningeal solitary fibrous tumor. AB - Solitary fibrous tumors (SFT's) are rare soft tissue neoplasms of mesenchymal origin, most commonly reported in the thoracic cavity. They exhibit an aggressive and infiltrative nature and have a tendency to recur either locally or distantly, the latter typically being a late event. Primary therapy consists of complete excision and prognosis is poor in case of recurrence. In this manuscript, we discuss the imaging features and treatment options for a patient presenting with delayed liver metastasis ten years after treatment for a meningeal SFT. PMID- 22319970 TI - Montelukast as a treatment modality for eosinophilic gastroenteritis. AB - Eosinophilic Gastroenteritis (EG) is a rare condition, caused by eosinophilic inflammatory infiltrates in the gastrointestinal tract. It is usually treated successfully with systemic glucocorticoids. Because of frequent relapses, however, there is need for alternatives. We describe a 38-year old man with steroid-dependent EG, who was successfully treated with montelukast, a leukotriene receptor antagonist. It inhibits leukotriene D4, an important cytokine in the inflammatory cascade. Although montelukast could not replace steroid therapy, it acted as a steroid sparing agent in our patient. Review of the literature shows that montelukast is efficient in the treatment of EG in a part of the patients. The low cost, the low number of side effects and its efficiency make it an interesting alternative in relapsing or steroid dependent EG. There is need for multicentric studies regarding the treatment of EG. PMID- 22319971 TI - Hepatic rhabdomyosarcoma in an adult: a rare primary malignant liver tumor. Case report and literature review. AB - Rhabdomyosarcomas are malignant tumors that display features of striated muscle differentiation. They are the most common soft-tissue sarcomas among children and young adults. In mature adults however there are very rare. The liver as a primary site in adults has only been described in 12 cases. We report a case of a primary alveolar rhabdomyosarcoma of the liver in a 59 year old female, confirmed by histological examination using immunohistochemical analysis (positive actin, desmin, vimentin and myogenin staining) and fluorescent in situ hybridization (FISH) analysis (positivity for PAX3/FOXO1A fusion). The patient underwent primary surgical resection, but presented a few weeks after surgery already with recurrent disease in the abdomen and bone metastasis. Despite initial good response to chemotherapy (doxorubicin/ifosfamide) and stable disease at 12 months after diagnosis, the patient died 31 months after the first presentation secondary to complicated abundant abdominal recurrent disease. We further present a review of the literature on published similar cases since 1979. PMID- 22319972 TI - Reversible sudden sensorineural hearing loss during chronic hepatitis C treatment with pegylated interferon/ribavirin. PMID- 22319973 TI - Ileocolonic involvement of follicular small cell lymphoma: a rare entity. PMID- 22319974 TI - Endoscopic and ultrasonographic diagnosis of intramural small bowel hematoma apparently caused by warfarin. PMID- 22319975 TI - Autoimmune hepatitis with anti SLA antibodies. PMID- 22319976 TI - Pegylated interferon associated lichen planus at the injection site. PMID- 22319977 TI - Military general practice-- the future for training and education. PMID- 22319978 TI - Role 2 afloat. PMID- 22319979 TI - The clinical outcome of UK military personnel who received a massive transfusion in Afghanistan during 2009. AB - OBJECTIVES: The UK Defence Medical Services has developed a Massive Transfusion Protocol (MTP) that forms part of the initial Damage Control Resuscitation process for severely injured combat casualties. The key objectives of this retrospective review of MTP recipients are to document the survival rates, level of critical care support required and the blood components transfused as part of the Massive Transfusion Protocol in Afghanistan during 2009. In addition to providing a measure of our current effectiveness it should also provide a reference point for future reviews as the MTP continues to evolve. METHODS: This was a collaborative project involving the Royal Centre for Defence Medicine and the Critical Care Department, University Hospitals Birmingham. It was limited to UK military personnel who were injured in 2009 and received massive transfusions (defined as the transfusion of 10 or more units of packed red blood cells over a 24-hour period) at Camp Bastion Role 3 Medical Facility, Afghanistan. RESULTS: During the 12-month period, 59 personnel received massive transfusions. 51 (86%) personnel survived to be discharged from hospital in the UK. 48 (92%) personnel required ventilatory support for a median of 3 (2-8) days. The longest period of ventilation was 40 days; 29 (55%) personnel required vasopressor support and eight personnel (15%) required renal replacement therapy. The median total transfusion of blood components was 45 (28.5-62) units. There were seven transfusions of more than 100 units. Five of the personnel in this group (including the recipient of a 237-unit transfusion) survived to be discharged from University Hospitals Birmingham. On average, 1.21 (SD 0.28) units of packed red blood cells were transfused for every unit of fresh frozen plasma. CONCLUSIONS: The use of the current MTP was associated with a high rate of survival. Survivors require a continuity of critical care with a median demand for 3 days. The early use of plasma and platelets can be successfully delivered in the battlefield despite operational and logistic constraints. PMID- 22319980 TI - Management of intestinal injury in deployed UK hospitals. AB - INTRODUCTION: Definitive laparotomy (DL), with completion of all surgical tasks at first laparotomy has traditionally been the basis of surgical care of severe abdominal trauma. Damage control surgery (DCS) with a goal of physiological normalisation achieved with termination of operation before completion of anatomical reconstruction, has recently found favour in management of civilian trauma. This study aims to characterise the contemporary UK military surgeon's approach to abdominal injury. PATIENTS AND METHODS: A retrospective analysis was performed on British service personnel who underwent a laparotomy for intestinal injury at UK forward hospitals from November 2003 to March 2008 as identified from the Joint Theatre Trauma Registry. Patient demographics, mechanism and pattern of injury and clinical outcomes were recorded. Surgical procedures at first and subsequent laparotomy were evaluated by an expert panel. RESULTS: 22 patients with intestinal injury underwent laparotomy and survived to be repatriated; all patients subsequently survived to hospital discharge. Mechanism of injury was GSW in seven and blast in 13. At primary laparotomy, as defined by the operating surgeon, 15/22 underwent DL and 7/22 underwent DCS. Mean Injury Severity Score (ISS) was 19 for DL patients compared to 29 for DCS patients (p = 0.021). Of the 15 patients undergoing DL nine had primary repair (suture or resection/ anastomosis), one of which subsequently leaked. Unplanned re-look was required in 4/15 of the DL cases. CONCLUSION: This review examines the activity of British military surgeons over a time period where damage control laparotomy has been introduced into regular practice. It is performed at a ratio of approximately 1:2 to DL and appears to be reserved, in accordance with military surgical doctrine, for the more severely injured patients. There is a high rate of unplanned relook procedures for DL suggesting DCS may still be underused by military surgeons. Optimal methods of selection and implementation of DCS after battle injury to the abdomen remain unclear. PMID- 22319981 TI - A brief history of war amputation. AB - Throughout the history of warfare, changes in weaponry have produced changes in the nature of war injury. The 16th century saw the introduction of firearms in conventional warfare, bringing the destructive power of weaponry to new and unseen heights with a dramatic increase in the severity and complexity of battle injuries. Destructive gunshot wounding associated with embedded foreign material often led to sepsis and demanded the more radical treatment of amputation. Over the past 500 years innumerable developments have taken place in anaesthesia, asepsis, transfusion therapy and resuscitation, antibiotic therapy, vascular surgery and wound management. Medical services have had to adapt in order to cope with the changing volume and changing nature of battle casualties resulting from modern weaponry. Despite the progress made, amputation is still a commonly performed operation following traumatic limb injury. In those cases where the decision to amputate is not so clearly and distinctly defined, history has shown that prevention of infection requires aggressive primary surgery and removal of all devitalised tissue. This paper examines the history of amputation in the management of the battlefield casualty suffering limb injury, beginning in the 16th century and continuing into present day. PMID- 22319982 TI - Use of hearing protection on military operations. AB - Noise Induced Hearing Loss (NIHL) continues to be a significant source of morbidity for UK service personnel. The Personal Interfaced Hearing Protection (PIHP) system was procured as an Urgent Operational Requirement primarily to provide a connection to the Personal Role Radio. Through its custom- mould design it was also expected to act as Personal Protective Equipment (PPE) against NIHL in a method that had not been possible previously. The aim of this paper was to evaluate user opinion of the four current methods of hearing protection including PIHP. 108 service personnel serving in a Forward Operating Base in Afghanistan were questioned anonymously using a paper-based questionnaire. The response rate was 78%, reflecting the difficulties in anonymous data collection in an environment such as this. PIHP was perceived to be more practical for use on the ranges or patrolling than the standard methods of hearing protection. Although only 4% were routinely wearing PIHP on patrol, this was related to understandable reluctance in wearing a new system that had only been issued immediately prior to this deployment. Early design problems highlighted by our study, such as changes in the design of the ear-piece to improve retention, have already been implemented. Compliance will be improved through a dedicated educational programme to explain its relevance. Despite the logistical difficulties in providing custom- made ear moulds, the PIHP system must be delivered to all service personnel early in their career so they are confident in its use long before operational deployment. Future research is required to ascertain the effectiveness of PIHP as a method of PPE in reducing the incidence of NIHL. PMID- 22319983 TI - General practice--reflection on five years of multidisciplinary training at Medical Centre Gutersloh. AB - BACKGROUND: Medical Centre Gutersloh is a primary care setting which provides the full range of general practice care for British Forces Germany Health Service (BFG HS). The aim of this article is to evaluate the multidisciplinary training organised by the author there, to exchange information and to provide suggestions for improvement and development. METHODS: Description of the training scheme and analysis of routinely collected management data. RESULTS: The training scheme is based on adult education principles with a focus on interactive learning. Over the period November 2005-July 2010 a total of 1201 members of staff from various disciplines participated in 86 documented training sessions. The majority of the attending staff considered the training to be relevant, interesting and well presented. A substantial proportion indicated that they would change their practice as a result of the training. These views remained stable over time. The majority of facilitators consisted of medical centre employees. CONCLUSIONS: This article provides an overview onfive years of multidisciplinary training in a general practice setting. Overall feedback from staff suggests that the training has been highly valued over those years. However, it is recognised that this evaluation has its limitations and suggestions are made regarding how these types of training schemes can be improved and developed further. PMID- 22319984 TI - General Duties Medical Officer with the British Forces in Cyprus. AB - The aim of this article is to describe the role and training of a General Duties Medical Officer (GDMO) based with the British Forces in Cyprus. PMID- 22319985 TI - Medical contribution to the comprehensive approach. AB - The coordination of the Military, Diplomatic and Economic/Development levers of power, the so-called "hard" and "soft" powers, to bring about the strategic aims of governments, supported by Non-Governmental Organisations and international organisations, is commonly known as the Comprehensive Approach (CA). The CA is now part of both NATO and UK military doctrine and concepts development. This article describes how medical branch HQ Allied Rapid Reaction Corp, as part of the HQs work to operationalise the CA, has sought and developed training opportunities to improve individual skill-sets to enable the branch to better contribute to the CA process. PMID- 22319986 TI - Don't forget the fragment! An unusual case of occult fragment embolisation following penetrating neck injury. AB - Fragment embolisation following vascular injury is uncommon. The case of a 31 year old soldier, who sustained a penetrating fragment injury to the neck with distal arterial embolisation, is presented and the discussion illustrates both the importance of expedient assessment and management of cervical vascular injuries and of thorough correlation of clinical and radiological findings to avoid missed emboli. PMID- 22319987 TI - Endoscopic evaluation of a complex ballistic injury. AB - The current conflict in Afghanistan is characterised by significant injuries resulting from the use of Improvised Explosive Devices. Increasing survivability from battlefield injury, escalating musculoskeletal ballistic trauma and the use of blast weaponry combine to produce an injury profile which defines contemporary combat casualty care. Such complex multi-system trauma challenges current wound care rationale. Ballistic injury of the perineum, often associated with proximal femoral injury and significant tissue loss, raises particular management difficulties. These cases demand an individualised, flexible approach due both to the extent of their wounds, logistical issues with positioning and often limited surgical approaches. Routine positioning and approaches around the pelvis may not be available to the surgical team due to presence of external fixators and tenuous skin bridges. The availability of donor skin to cover soft tissue defects is limited and as such, approaches to wounds with minimal additional tissue trauma are of particular use. We describe the benefits of endoscopic techniques and equipment in the evaluation and management of such an injury. PMID- 22319988 TI - Body contouring surgery for military personnel following massive weight loss. AB - The burgeoning global obesity epidemic extends to the military service, where 6 53% of military personnel are overweight. Obese military personnel who adhere to a strict training and diet regime may potentially achieve and maintain significant weight loss. They may however face physical problems such as excess skin folds causing discomfort, difficulty in uniform fitting, personal hygiene, interference with full physical activities and psychological issues such as body image dissatisfaction, low self esteem and difficulty in social acceptance. We present a case report of a highly motivated military conscript who achieved and maintained significant weight loss but had physical defects following Massive Weight Loss. Body contouring surgery was successfully utilised to correct his physical defects and allowed him to return to full physical duties. PMID- 22319989 TI - Proceedings of the DMS medical ethics symposium. AB - This article presents the proceedings of a symposium on medical ethics held at the Royal Centre for Defence Medicine in October 2010. The nature of current operations continually generates challenging ethical problems, many of which are unique to the military environment. This article is intended to generate a debate on these difficult issues and readers are encouraged to contribute to this debate by emailing the Editor. PMID- 22319990 TI - The wars in Africa--part 2. PMID- 22319991 TI - A review of dental injuries in a military hospital in Turkey. PMID- 22319992 TI - Collective and corporate memory in the defence medical services. PMID- 22319993 TI - Sickle cell trait and haemoglobinopathies. PMID- 22319994 TI - Extremity compartment syndrome with Sickle Cell Trait. PMID- 22319995 TI - A pre-hospital technique for controlling haemorrhage from traumatic perineal and high amputation injuries. AB - Perineal trauma resulting from the adaptive use of improvised explosive devices (IEDs) has become an increasingly common problem during current operational conflicts in Afghanistan. Control of haemorrhage from the perineum and high amputations is a particular challenge due to the bony anatomy, rich pelvic vascular supply and the difficulty in achieving haemostasis by direct pressure. In this article, the authors describe a potential pre-hospital solution for controlling haemorrhage from perineal and high amputation injuries. PMID- 22319996 TI - Expert evidence accountability: new developments and challenges. AB - A series of developments in relation to the accountability of expert witnesses and the admissibility of their opinions is taking place. This extends to encroachments in the United Kingdom on expert witness immunity, the imposition of disciplinary liability for registered health practitioners in Australia and the United Kingdom, and recommendations from the United Kingdom Law Commission for a systematised procedure for reliability determination as a prerequisite for admissibility rulings. This combination of measures is indicative of international concern about the contemporary role of expert witnesses. It highlights the need for both empirical information about whether the anecdotal and experiential concerns about expert evidence are well-founded and for the provision of better and clearer guidance to experts and litigators alike about the underpinnings and methodologies that are permissible for admissible and probative expert opinions. PMID- 22319997 TI - Laws to detain individuals with substance dependency: breaching human rights or restoring health? AB - At the turn of the 20th century in the United Kingdom and Australia, legislation was introduced to detain and treat "inebriates". Since that time, variations of such laws have continued to exist. This column examines current laws in Australia and New Zealand with a particular focus on recent law reform efforts in New South Wales and Victoria. The column raises some of the issues with these laws in relation to breaching human rights for the purpose of treatment. PMID- 22319998 TI - Access to expensive anti-cancer drugs. AB - Expensive anti-cancer drugs expose controversy underlying the process for resource allocation decisions, and intermittently result in marked publicity, emotive discussions about access to novel and expensive treatments, and political involvement which may override existing processes. This column outlines the methods of determining whether or not a treatment is considered appropriate to fund, and focuses upon the evidence of patient and doctor wishes. The existing research illustrates the complexity of patient and oncologist decision-making when these drugs are to be considered. Past litigation to obtain access to expensive treatments is discussed, along with the interactions between patients, pharmaceutical companies, health services and oncologists. This evolving field is being transformed by developments in molecular biology enabling targeted drugs, and amply demonstrates the complexity of funding decisions and how expensive treatments are considered by a range of stakeholders. PMID- 22319999 TI - Living and learning during an ethical crisis in medicine. AB - The Cartwright Report was released at a time of massive ethical change in New Zealand medicine, the shock waves spreading throughout the region as they caught the surge of interest in patient autonomy and patient rights. The mood was as revolutionary for health professionals as the late 1960s and 1970s were for society in general, with many established patterns of practice and everyday expectations about the nature of clinical care being challenged and disrupted. For some of us who witnessed the medico-legal impact of the report in Australasia, it revived memories of our time as medical students when the events reported on were being played out. Looking back now on a time of moral crisis in medicine has lessons to teach us which have a timeless quality about them as they recall the dim distant days of Semmelweiss and other doctors struggling at a political fringe of the profession. PMID- 22320000 TI - The growing role of carers in the administration of medications. AB - The roles of registered nurses, enrolled nurses, nurse practitioners and midwives in the administration of medications are subject to the legislation and regulation in their respective States and Territories in Australia. Underpinning this regulatory framework is a presumption that health professionals who come under the relevant legislation and regulations have attained the levels of competency, skill and knowledge consistent with professional standards and the protection of the public. This column considers the provisions of the Health (Drugs and Poisons) Regulation 1996 (Qld) addressing the administration of controlled and restricted drugs in light of a recent Queensland Civil and Administrative Tribunal decision. PMID- 22320001 TI - Condliff v North Staffordshire Primary Care Trust: can human rights redress inequities in United Kingdom and Australian cost-containment-driven health care reforms? AB - A recent case from the English Court of Appeal (R (on the application of Condliff) v North Staffordshire Primary Care Trust [2011] EWCA Civ 910, concerning denial by a regional health care rationing committee of laparoscopic gastric bypass surgery for morbid obesity) demonstrates the problems of attempting to rely post hoc on human rights protections to ameliorate inequities in health care reforms that emphasise institutional budgets rather than universal access. This column analyses the complexities of such an approach in relation to recent policy debates and legislative reform of the health systems in the United Kingdom and Australia. Enforceable human rights, such as those available in the United Kingdom to the patient Tom Condliff, appear insufficient to adequately redress issues of inequity promoted by such "reforms". Equity may fare even worse under Australian cost-containment health care reforms, given the absence of relevant enforceable human rights in that jurisdiction. PMID- 22320002 TI - Australian and New Zealand governments agree to proceed with the joint regulatory agency for therapeutic products. PMID- 22320003 TI - Global artificial photosynthesis project: a scientific and legal introduction. AB - With the global human population set to exceed 10 billion by 2050, its collective energy consumption to rise from 400 to over 500 EJ/yr and with the natural environment under increasing pressure from these sources as well as from anthropogenic climate change, political solutions such as the creation of an efficient carbon price and trading scheme may arrive too late. In this context, the scientific community is exploring technological remedies. Central to these options is artificial photosynthesis--the creation, particularly through nanotechnology, of devices capable to doing what plants have done for millions of years - transforming sunlight, water and carbon dioxide into food and fuel. This article argues that a Global Artificial Photosynthesis (GAP) project can raise the public profile and encourage the pace, complexity and funding of scientific collaborations in artificial photosynthesis research. The legal structure of a GAP project will be critical to prevent issues such as state sovereignty over energy and food resources and corporate intellectual monopoly privileges unduly inhibiting the important contribution of artificial photosynthesis to global public health and environmental sustainability. The article presents an introduction to the scientific and legal concepts behind a GAP project. PMID- 22320004 TI - Is there still a place for gene patents in Australia? Implications of recent United States and European case law. AB - This article considers the ramifications of recent United States and European litigation relating to patents claiming rights to genes associated with hereditary forms of breast cancer (the so-called BRCA genes) for recently commenced Australian litigation relating to the same subject matter. The article is contextualised with brief summaries of the relevant patent law, the science of genetics, the history of the BRCA genes and an overview of the activities of the patent holder. The analysis of first instance and appeal decisions on the validity of the United States BRCA patents shows the final outcome is still highly uncertain in that jurisdiction, while the European litigation provides little assistance in predicting the outcome of the Australian action. This article concludes that the outcome of the Australian litigation is an issue that cannot be determined with any certainty due to the lack of specific, relevant precedents both in Australia and in other jurisdictions. PMID- 22320005 TI - Legal impediments to data linkage. AB - Large numbers of electronic health data collections have been accumulated by both government and non-government agencies and organisations. Such collections primarily assist with the management of health services and the provision of health care programs, with only a minority of these data collections also intended for research purposes. A number of constraints are placed on access to such data for the purposes of research, including data linkage. This article examines those factors arising from the intricacies of Australia's privacy legislation landscape which impede access to such collections. The relevant issues discussed include issues relating to the existence of multiple privacy and health privacy Acts, the recommendations made by the Australian Law Reform Commission in relation to the Privacy Act 1988 (Cth) and the constraints placed on the conduct of data-linkage research which arise from legislation that relates specifically to certain data collections. PMID- 22320006 TI - Sub-Saharan African randomised clinical trials into male circumcision and HIV transmission: methodological, ethical and legal concerns. AB - In 2007, WHO/UNAIDS recommended male circumcision as an HIV-preventive measure based on three sub-Saharan African randomised clinical trials (RCTs) into female to-male sexual transmission. A related RCT investigated male-to-female transmission. However, the trials were compromised by inadequate equipoise; selection bias; inadequate blinding; problematic randomisation; trials stopped early with exaggerated treatment effects; and not investigating non-sexual transmission. Several questions remain unanswered. Why were the trials carried out in countries where more intact men were HIV-positive than in those where more circumcised men were HIV-positive? Why were men sampled from specific ethnic subgroups? Why were so many participants lost to follow-up? Why did men in the male circumcision groups receive additional counselling on safe sex practices? While the absolute reduction in HIV transmission associated with male circumcision across the three female-to-male trials was only about 1.3%, relative reduction was reported as 60%, but, after correction for lead-time bias, averaged 49%. In the Kenyan trial, male circumcision appears to have been associated with four new incident infections. In the Ugandan male-to-female trial, there appears to have been a 61% relative increase in HIV infection among female partners of HIV-positive circumcised men. Since male circumcision diverts resources from known preventive measures and increases risk-taking behaviours, any long-term benefit in reducing HIV transmission remains uncertain. PMID- 22320007 TI - Is it lawful to use Medicaid to pay for circumcision? AB - Since 1965, tens of millions of boys have been circumcised under the Medicaid program, most at birth, at a cost to the United States Federal Government, the States and taxpayers of billions of dollars. Although 18 States have ended coverage since 1982, the United States Government and 32 States continue to pay for non-therapeutic circumcision, even though no medical association in the world recommends it. Many cite American medical association policy that the procedure has potential medical benefits as well as disadvantages, and that the circumcision decision should be left to parents. This article shows that Medicaid coverage of circumcision is not a policy issue because it is prohibited by federal and State law. As American medical associations concede, non-therapeutic circumcision is unnecessary, elective, cosmetic surgery on healthy boys, usually performed for cultural, personal or religious reasons. The fundamental principle of Medicaid law is that Medicaid only covers necessary medical treatments after the diagnosis of a current medical condition. Physicians and hospitals face severe penalties for charging Medicaid for circumcisions. Medicaid officials and the Federal and State Governments are also required to end coverage. It is unlawful to circumcise and to allow the circumcision of healthy boys at the expense of the government and taxpayers. PMID- 22320008 TI - Psycho-social, ethical and legal arguments for and against the retrospective release of information about donors to donor-conceived individuals in Australia. AB - In the February 2011 report on its inquiry into the past and present practices of donor conception in Australia, the Australian Senate Legal and Constitutional Affairs References Committee called for the introduction of legislation to regulate donor conception in all jurisdictions that do not have it in place "as a matter of priority". It further called for the establishment, "as a matter of priority", of a national register of donors to enable donor-conceived individuals to access identifying information about their donor. The Senate Committee left open the question as to whether the legislation and central register should have retrospective effect. This article focuses upon that question. It shows that arguments concerning the privacy, confidentiality and anonymity of some donors who may wish to remain anonymous are outweighed by the manifest injustice faced by donor-conceived individuals who are denied access to such information, as well as their families and donors who wish to exchange this information, PMID- 22320009 TI - Balancing public health and practitioner accountability in cases of medical manslaughter: reconsidering the tests for criminal negligence-related offences in Australia after R v Patel. AB - In 2010 Dr Jayant Patel was convicted of several offences on the basis of criminal negligence. Following the Queensland Court of Appeal's 2011 endorsement of the trial judge's decision, the case provides a timely opportunity to review prosecutions for medical negligence criminal offences throughout Australia and to critically examine the tests in assessing whether the balance has been correctly struck. The author argues that the thresholds required for prosecutions for criminal negligence for medical manslaughter are problematic and unduly onerous, and do not adequately strike the balance between the utilitarian value in health care and patient safety, on the one hand, and practitioner accountability and deterrence, on the other. This article considers reforms to remedy the imbalance, including a reformulation of the Criminal Code (Qld) and common law thresholds, proposals for the enactment of a separate offence of criminally negligent manslaughter and the utilisation of corporate prosecutions for manslaughter liability to broaden accountability in health care and promote patient safety on a systemic level. PMID- 22320010 TI - Trafficking in persons and victim health in Australia. AB - This article explores the health problems experienced by victims of trafficking in persons in Australia and analyses the domestic support schemes established to assist these victims. It focuses specifically on the health of adult, female victims who constitute the majority of identified victims, and who are the principal recipients of government support services. Domestic experiences and support schemes are reviewed in the light of international law and best practice guidelines. Recommendations are made to improve the health services available to victims of trafficking in persons in Australia. PMID- 22320011 TI - Putting health first. PMID- 22320012 TI - Ancillary providers aren't always the answer. PMID- 22320013 TI - Internet based telepsychiatry: a pilot case in Somaliland. PMID- 22320014 TI - Iraqi community members' knowledge, attitude and practice of emergency medical care: assessing civilian emergency medicine in an area of conflict. AB - The objective of this article is to assess community member knowledge, attitude, and practice of emergency medical care in Baghdad, Iraq. We performed a randomized, cluster-based, household Knowledge, Attitude, and Practice (KAP) survey regarding pre-hospital and hospital-based emergency medical care among Baghdad community members. A total of 1172 individuals participated in the survey. While most (93.5%) understood that for a serious injury, one should go to the hospital within three hours, only half (50.6%) felt that ambulances were beneficial and only 5% knew that there was a number to call in case of medical emergency. Regarding attitudes, only half (50.2%) of those interviewed felt an ambulance would arrive within an hour, while higher proportions of people believed that paramedics (59.1%) and medical staff working in emergency departments were adequately trained (71.5%). In terms of practice, most Iraqis responded that they would seek care in a hospital (84.8-90.0%) by means other than an ambulance (98.0-99.2%). However, if an ambulance arrived, 77% would allow it to transport their friends/family and 73.5% would trust the medical staff in the hospital to appropriately treat them. Our conclusion is that emergency medical care in Iraq is still in the development phase. Although numerous ambulances have been commissioned, scores of paramedics have been trained, and staff working in Baghdad Emergency Departments have undergone updates in their practice, the public does not appear to be fully informed of these changes. Future developments in Iraqi emergency medical care should include targeted efforts to expand the public awareness of such services. PMID- 22320015 TI - Highly active anti-retroviral therapy in the prevention of mother-to-child transmission of HIV in rural Zimbabwe during the socio-economic crisis. AB - The purpose of this study is to evaluate the effectiveness of highly active antiretroviral therapy (HAART) in preventing mother-to-child transmission (PMTCT) of HIV in breastfeeding women in rural Zimbabwe. During a severe socio-economic crisis in 2005-2007, 82 eligible HIV-positive pregnant women between 14-36 weeks gestation were initiated on HAART with AZT/3TC/nelfinavir combination therapy at a rural hospital and continued through to six months post-partum. In addition, mothers also received intrapartum single-dose nevirapine (sdNVP). Infants received sdNVP/AZT in the first 72 hours and were assessed for HIV infection at six weeks of age. Results were compared to historical controls of HIV-positive pregnant women who received sdNVP only at the same center. Of the 67 infants with available data on HIV status at six weeks postpartum, three (4.4%) were HIV positive by HIV RNA assay in the HAART + sdNVP group compared to 49/297 (16.5%) in the sdNVP group (p = 0.01). HAART given to HIV-infected mothers in pregnancy and during breastfeeding along with intrapartum sdNVP resulted in a lower postnatal HIV transmission at six weeks postpartum compared to sdNVP treatment. Our HAART regimen demonstrates that PMTCT of HIV can be effective even during times of socioeconomic crisis in resource-poor rural settings. PMID- 22320016 TI - Evaluation of bloodsucking arthropod bite as possible risk co-factor in Human herpesvirus-8 transmission route. AB - Human herpesvirus-8 non-sexual transmission occurs primarily from mother-to child. The viral load in saliva is higher than in other human fluids. Moreover, there is evidence that bloodsucking arthropod bites induce an inflammatory/immune response that facilitates viral replication. We aim to explore possible risk factors in mother-to-child HHV-8 transmission associated with traditional methods which involve the use of saliva to relieve the irritation and skin reaction caused by arthropod bites. We administered questionnaires to 2244 children from several African countries and Italy. Descriptive statistics and logistic regression were used in the analysis of the answers to evaluate the relationships between the use of traditional methods and other risk factors. The use of traditional methods is high in Cameroon (63.0%) and Uganda (39.9%), intermediate in Senegal (26.7%) and Italy (21.7%), low in Madagascar (6.7%). Statistical analyses show significant direct relationships between the use of traditional methods, skin reactions to the bite and their duration in Cameroon, Uganda and Senegal. The use of saliva and herbs applied by the mothers on the child's skin, is a common habit in Africa. If this practice plays a role in the HHV-8 transmission, then, it could provide the basis for interventions capable of reducing the health impact of the infection in children in tropical areas. PMID- 22320017 TI - Malarial infections in sedentary and migratory passerine birds in Israel: description of new species. AB - Our objective was to investigate the diversity of Plasmodium species in birds of the Rift Valley section in Israel. Plasmodium merulae Corradetti & Scanga, 1973 was previously reported in blackbirds (Turdus merula Linnaeus, 1758), that are resident. We also report and describe three other species and seven new species of Plasmodium from migratory birds in the north, and from Eilat at the southernmost tip of the Jordan Valley. New species are: Plasmodium lusciniae sp. n., Plasmodium alloreticulatus sp. n. and Plasmodium paranuclearis sp. n. from Luscinia svecica (Linnaeus, 1758), Plasmodium phoenicuri sp. n., Plasmodium reticulatus sp. n. and Plasmodium synnuclearis sp. n. from Phoenicurus phoenicurus (Linnaeus, 1758), and Plasmodium bilobatus sp. n. from Acrocephalus schoenobaenus (Linnaeus, 1758). The morphological affinities among the new described species and between P merulae and Plasmodium vaughani Novy & MacNeal, 1904 are highlighted and discussed. The host birds belong to two families: Muscicapidae (Turdus merula, Luscinia svecica and Phoenicurus phoenicurus) and Sylviidae (Acrocephalus schoenobaenus). All the parasites species are affiliated to the so-called "vaughani complex" (Corradetti & Scanga 1973) which are small parasites that possess a characteristic refractile globule in their cytoplasm. PMID- 22320018 TI - Coccidiosis of wild and captive European mouflons (Ovis aries) living in a natural reserve of central Italy. AB - Between December 2005 and November 2006, a survey on coccidiosis of wild and captive mouflons living in the Orecchiella Natural Reserve (Tuscany, Italy) was performed on faecal samples collected approximately every two months. A total of 96 samples were collected, 55 of which from wild mouflons and 41 from captive mouflons. On these faecal samples qualitative and quantitative parasitological analyses were performed; moreover, faecal cultures were made in order to identify the involved Eimeria species. Significantly higher prevalence (%) and mean intensity (mean OPG +/- SD) of coccidian infection resulted for captive mouflons (73.17% and 814.6 +/- 1297.2 OPG) comparing to wild mouflons (36.73% and 112.7 +/ 268.7 OPG). Eimeria parva, E ovinoidalis, E. bakuensis, E. ahasata, E. intricata, E. crandallis, E. granulosa, E. faurei and an Eimeria species very similar to the descriptions previously reported for E. arloingi and E. yakimoffmatschoulsky, were isolated. PMID- 22320019 TI - Population fluctuation of soil and plant parasitic nematodes at Khangabok Wangbal Government silkfarm, Wangbal, Thoubal district Manipur, India. AB - The population fluctuation of nematodes around the rhizospheric regions of mulberrry plants at Khangabok Wangbal Government Silk farm, Wangbal, Thoubal District, Manipur, India was studied in relation to environmental factors like soil moisture content, soil pH, soil temperature, rainfall and moisture content of air for a consecutive period of three years, 2006-2008. During 2006, nematode population was highest in the month of May with very high rainfall (174.2 mm). Positive correlation of nematode population was found with soil temperature, soil pH, rainfall and relative humidity and negative correlation with soil moisture. During 2007, nematode population was highest in the month of May with least soil moisture and highest rainfall (15.1 p.c. and 190.6 mm). Nematode population had positive correlations with soil moisture, temperature, pH, rainfall and relative humidity of air. During 2008, nematode population was highest in the month of April with highest soil temperature of 24.8 degrees C, 66.0 p.c. moderate relative humidity and 21.0 mm rainfall. There were positive correlation with soil temperature and pH, and negative correlation with soil moisture, rainfall and relative humidity. Lowest nematode population was found during January (2006), and during December (2007, 2008) there were negligible rain and sometimes no rainfall at all. Among all dorylaimids, tylenchids, aphelenchids and mononchids, Helicotylenchus sp. pertain the most numerous nematode species in all the three years and seasons. PMID- 22320020 TI - Cutaneous myiasis in a geriatric patient. AB - Cutaneous myiasis in humans involving fly species endemic in Italy are uncommon and are not often present in the literature. In the present article we describe the case of cutaneous myiasis in a woman brought to the Emergency Department (ED) of the S. Croce e Carle General Hospital in Cuneo, northwest Italy. The patient was in precarious hygienic condition, and was suffering from localized ulcerated foot ulcers with significant inflammation extending up to the knee. Fly larvae, subsequently identified as Lucilia sericata (Meigen, 1826), were found in the lesions. The patient was admitted to the Department of Internal Medicine where she was treated with antibiotics and the lesions were medicated, resulting in full recovery. PMID- 22320021 TI - First record of Paradiplozoon amurensis (Monogenea: Diplozoidae) in Iraq from gills of the cyprinid fish Cyprinion macrostomum. AB - A survey of gill parasites was conducted in 164 Cyprinion macrostomum (Cyprinidae) collected from the Tigris River at Tikreet city, Salah Al-Deen province, in central Iraq, in 2009-2010. The monogenean Paradiplozoon amurensis Akhmerov, 1974 (Diplozoidae) was observed in the gills of 26.2% of these fishes with a mean intensity of 2.3. This is the first report of P amurensis in Iraq. A description and morphometrics of P amurensis specimens are presented. PMID- 22320022 TI - [Atti della Societa per gli Studi della Malaria. Vol. XI. 1910. On the pathogenesis of recurrence in malarial fever]. PMID- 22320023 TI - Beliefs and attitudes about prescribing opioids among healthcare providers seeking continuing medical education. AB - OBJECTIVE: The purpose of this study was to assess the beliefs and attitudes of healthcare providers about prescribing opioids for chronic pain. SETTING: The setting was a continuing medical education conference that was specifically designed to deliver content about chronic pain and prescription opioids to providers without specialty expertise in pain medicine. PARTICIPANTS: Conference attendees with prescribing privileges were eligible to participate, including physicians, physician assistants, and advance practice nurses. INTERVENTION: Study participants completed a questionnaire using an electronic response system. MAIN OUTCOME MEASURES: Study participants completed a validated questionnaire that was specifically developed to measure the beliefs and attitudes of healthcare providers about prescribing opioids for chronic pain. RESULTS: The questionnaire was completed by 128 healthcare providers. The majority (58 percent) indicated that they were "likely" to prescribe opioids for chronic pain. A significant proportion of respondents had favorable beliefs and attitudes toward improvements in pain (p < 0.001) and quality of life (p < 0.001) attributed to prescribing opioids. However, a significant proportion had negative beliefs and attitudes about medication abuse (p < 0.001) and addiction (p < 0.001). Respondents also indicated that prescribing opioids could significantly increase the complexity of patient care and could unfavorably impact several administrative aspects of clinical practice. CONCLUSIONS: The beliefs and attitudes identified in this study highlight important educational gaps that exist among healthcare providers about prescribing opioids. Knowledge of these educational gaps could build the capacity of medical educators to develop targeted educational materials that could improve the opioid prescribing practices of healthcare providers. PMID- 22320024 TI - Primary care survey of the value and effectiveness of the Washington State Opioid Dosing Guideline. AB - PURPOSE: To evaluate the acceptability and usefulness of the Washington State Opioid Dosing Guideline (Guideline) developed for primary care providers for the treatment of chronic noncancer pain. The Guideline contains innovative tools, such as an online dosing calculator, and recommendations to assist providers, including a "yellow flag" threshold of 120 mg/d morphine equivalent dose (MED) at which specialty consultation is recommended. METHODS: Using a convenience sample, an anonymous web-based survey was conducted among primary care providers in Washington (WA) state. Physician/ administrative leaders in four regional and two statewide healthcare systems and associations distributed the electronic links to primary care providers in their organizations. RESULTS: Six hundred fifty-five (n) providers completed the survey representing 20 percent of the total number contacted. The majority (89 percent) of providers in this sample treat chronic pain patients, and more than half (54 percent) have frequent concerns about addiction, tolerance, and diversion. Forty-five percent had read and applied the Guideline in their practice. The majority of these providers found the Guideline to be helpful and 86 percent find the threshold of 120 mg/d MED dose reasonable or too high. Some key best practices such as tracking pain and function using structured instruments and use of urine drug testing are infrequently used. CONCLUSIONS: Results from this survey suggest that the recommendations and tools given in the Guideline, including the threshold of 120 mg/day MED dose, are acceptable and useful to a large majority of primary care providers in WA state. Substantial additions to the Guideline based on needs identified in this survey were added in June 2010 and wider dissemination is planned. PMID- 22320025 TI - Improvement of pain physicians' practices of opioid management: population-based urinary excretion data. AB - BACKGROUND: Physicians treating patients for chronic pain have limited means of determining whether a person is taking their medications as prescribed and are not taking extra medication. Complicating patient treatment regimens is the fact that pain physicians' prescribing practices may come under scrutiny by the Drug Enforcement Agency and other licensing agencies. If questioned, doctors can be hard-pressed to substantiate that their particular practices meet the established standard of care. It would be helpful to establish that their patients adhere to medications when compared with other practices. Previous studies show that urinary excretion data transformed by mathematical models can produce a reliable range of expected values for pain medications and may be useful to help resolve the aforementioned issues. PURPOSE OF THE STUDY: To provide comparative urinary excretion information data on three commonly prescribed opioid medications (morphine, hydrocodone, and oxycodone). METHODS: This retrospective study involved quantitative analysis of300, 000 urine specimens for three test drugs using previously described methods. The results were analyzed as percent frequency distributions and logarithmic functions. RESULTS: The authors established a creatinine-normalized range of urinary concentration values for each drug. Results for two practices were compared with the meta-findings, providing quantitative evidence of overall standard of care prescription practice by that physician. CONCLUSIONS: Expected urinary drug excretion values for morphine, hydrocodone, and oxycodone can potentially benefit pain physicians by showing that they are within the expected standard of care, helping to establish patient compliance, and identifying patients whose metabolism of these drugs may put them at risk. PMID- 22320026 TI - Opioid-dependent error processing. AB - OBJECTIVE: To evaluate error processing in contrasting opioid treatment samples by finding the relative risk of fatal dosing errors leading to opioid overdose in a controlled cohort of detoxified patients with opioid dependence. METHODS: Data linkage was performed between the Western Australian deaths register and recorded admissions to the Perth Naltrexone Clinic and community-based methadone program. Death register and corresponding data of coronial findings for all the patients who were treated with rapid opioid detoxification under sedation and oral naltrexone were compared with corresponding data for all the patients who were prescribed methadone over a 2-year period. RESULTS: Data for naltrexone-treated patients (n = 1,097) and community-based methadone-treated patients (n = 2,520) showed mortality rates to be 2.6 percent per year for naltrexone treatment when compared with O.7 percent for methadone treatment (p < 0.001). This was due to 4.3 times the relative risk of death from opioid toxicity for naltrexone-treated patients (p < 0.001). CONCLUSIONS: Naltrexone increases vulnerability to overdose as enhanced opioid effects following neuroanatomical blockade can reverse behavioral tolerance and lead to greater fatal dosing errors on reinstatement of opioid dependence. PMID- 22320027 TI - Evaluation of the reinforcing and subjective effects of heroin in combination with dextromethorphan and quinidine. AB - OBJECTIVE: Studies have suggested that the N-methyl-D-aspartate antagonist dextromethorphan may be useful in the treatment of opioid dependence. DESIGN: This double-blinded, placebo-controlled inpatient study evaluated the effects of 0, 30, and 60 mg of dextromethorphan and quinidine (DMQ) on the reinforcing and subjective effects of heroin in recently detoxified heroin abusers. PARTICIPANTS: Nine heroin-dependent participants were admitted and then detoxified from heroin over the course of several days. INTERVENTIONS: Participants were subsequently stabilized on 0, 30, or 60 mg of DMQ. Each dose of DMQ was administered for two consecutive weeks, and the effects of heroin (0, 12.5, and 50 mg) were studied under each DMQ maintenance dose condition. DMQ and heroin dose were administered in random order both within and between participants. RESULTS: Planned comparisons revealed statistically significant increases in progressive ratio breakpoint values and positive subjective ratings as a function of heroin dose. There were no consistent changes in any of the responses as a function of DMQ maintenance dose, other than a modest reduction in craving. CONCLUSIONS: In summary, results from this study suggest that maintenance on dextromethorphan in combination with quinidine has a limited role in the treatment of opioid dependence. PMID- 22320028 TI - Plasma cyclic guanosine 3',5'-monophosphate levels: a marker of glutamate-nitric oxide-guanyl cyclase activity? AB - OBJECTIVES: Remifentanil-based anesthesia can lead to acute opioid tolerance and/or hyperalgesia. A low-dose intraoperative infusion of the N-methyl-D aspartate (NMDA) receptor antagonist ketamine did not result in reduced postoperative morphine consumption after remifentanil-based anesthesia in adolescents. This study investigates the potential role of the glutamate-nitric oxide-cyclic guanosine 3'5'-monophosphate (cyclic GMP) pathway in the failure of low-dose ketamine to prevent remifentanil-induced acute opioid tolerance and/or hyperalgesia. DESIGN AND SETTING: Prospective, double-blind, placebo-controlled randomized clinical trial at a university teaching hospital. PATIENTS, PARTICIPANTS, AND INTERVENTIONS: Thirty-four adolescents receiving remifentanil based anesthesia for surgical correction of idiopathic scoliosis were randomly assigned to receive either intraoperative ketamine administered as a bolus dose of 0.5 mg/kg in 10 mL of normal saline and a continuous intravenous infusion of 4.0 microg/kg/min or an equal volume of saline. MAIN OUTCOME MEASURES: Blood samples were collected before and after the administration of ketamine for analyzing the concentrations of cyclic GMP, ketamine, and norketamine. Blood samples were analyzed using high-performance liquid chromatography and an enzyme immunoassay. RESULTS: The median (interquartile range) value of the concentration of plasma cyclic GMP decreased from 23.7 (17.4-26.7) to 14.8 (14.0-17.3) nmol/L after ketamine infusion (p < 0.005) and from 23.9 (16.3-29.2) to 163 (14.5-18.6) nmol/L after saline infusion (p < 0.005). The median value of the concentration of plasma cyclic GMP at the end of ketamine infusion did not differ significantly when compared with that after saline infusion (p = 0.07). The concentration of plasma cyclic GMP was inversely correlated with the concentration of plasma ketamine (r = -0.61). CONCLUSIONS: This study suggests that the low dose of intraoperative ketamine infused was insufficient to suppress the NMDA receptor pathway. The concentrations of plasma cyclic GMP may serve as an indirect biological marker of ketamine-induced NMDA receptor antagonism. PMID- 22320029 TI - Assessment, stratification, and monitoring of the risk for prescription opioid misuse and abuse in the primary care setting. AB - OBJECTIVES: To evaluate potential for and incidence of aberrant drug-related behaviors among patients with chronic, moderate-to-severe pain in a primary care setting and to determine investigator compliance with universal precautions (UP) approach to pain management. DESIGN: Open label, multicenter. SETTING: Primary care centers (N = 281) across the United States. PATIENTS: Opioid naive and opioid experienced with chronic, moderate-to-severe pain (N = 1,487). INTERVENTIONS: Morphine sulfate extended-release capsules for < or = 4 months. Tools comprising UP approach were treatment agreement, card for obtaining/tracking prescriptions, Screener and Opioid Assessment for Patients with Pain-Revised questionnaire, pill counts, pain-patient follow-up tool, investigator assessment/plan, and urine drug screens (UDSs). OUTCOME MEASURES: Proportion of patients at low, moderate, and high risk of opioid misuse/abuse based on prespecified criteria and investigator judgment, proportion of patients with aberrant drug-related behaviors, and proportion of investigators compliant with UP approach. RESULTS: Patients were primarily white (87 percent), women (57 percent); mean age, 53 years (range, 21-92years). At baseline, 47 percent were considered low risk for opioid misuse/abuse, 52 percent moderate, and 1 percent high. UDSs were positive for illicit/nonprescribed drugs in a proportion of patients throughout the study. Overall, 64 percent of investigators were compliant with major components of UP approach in > or = 75 percent of their patients. However, there was a tendency for investigators to assign risk levels for opioid misuse/abuse as lower than protocol specified. CONCLUSIONS: Most patients in these primary care study centers were categorized as at least moderate risk for opioid misuse/abuse at baseline. Most primary care investigators complied with the UP approach to pain management and risk assessment. The completion of the brief training and clinical use of the tools during the study led to retained behavior change, but there was a tendency for investigators to assign lower risk levels than those that were protocol specified, suggesting a need for better understanding of factors influencing investigator decisions. PMID- 22320030 TI - Ideas and innovations: inclusion of pharmacists in chronic pain management services in a primary care practice. AB - Nonmalignant chronic pain management involves an ongoing process of complex evaluations including proper patient selection, proper prescribing, and careful monitoring. In the Pain Management Refill Clinic, patients are stabilized on an opioid regimen by either a pain specialist or a primary care physician (PCP). The PCP assumes long-term prescription of the regimen and proper follow-up. The inclusion of pharmacists in the management of patients suffering from chronic pain has allowed the physicians to improve opioid prescribing, documentation, and monitoring in accordance with chronic nonmalignant pain guidelines. PMID- 22320031 TI - [Tuberculosis pulmonum--"threaten us of epidemic"?]. AB - Tuberculosis (TB) remains a deadly infectious disease affecting millions of people worldwide with 95% of cases and 98% of deaths occuring in developing countries (9 milion new cases, 1 million deaths annually) vs.WHO. Tuberculosis is on the increase in developed countries, because of AIDS, the use of immunosuppresive drugs which depress the host defence mechanism, decreased socioeconomic conditions, as well as increased immigration of persons from areas of high endemicity. The major reason for this increase was because of rapid rise in cases from sub-Saharan Africa (due to AIDS) nad Russia. Incidense of tuberculosis in Poland 2007--the number of notified cases was 8014. Pulmonary cases represented 92.7% of total all TB cases and 628 cases of extrapulmonary TB. Chidren TB cases represented 0.9% (74 cases) of all cases notified in Poland. The incidence of tuberculosis increases with age from 1.1 in children do 41.2 among 65 and older. The incidence of men (31.5) was two times higher than in women- 14.5 per 100 000 respectivly. There were 716 deaths due to pulmonary TB and 23 from extrapulmonary TB. Multidrug resistance (MDR) of Mycobacterium tuberculosis is a major therapeutic problem, in the world, with a high mortality and occurs mainly in HIV-infected patients. The WHO estimates that around 50 million people are infected with MDR-TB! WHO suggest that a greater investment in the establishment treatment strategy of DOTS (Directly Observed Treatment Short course) into all posible regions. PMID- 22320032 TI - [Usefulness of examinations of serum levels of matrix metalloproteinases 1, MMP 3, MMP-9, tissue inhibitor of metalloproteinases 1, hyaluronic acid and antibodies against cyclic citrullinated peptide in Lyme arthritis, rheumatoid arthritis and patients with arthritic complaints]. AB - Lyme disease is a multisystem disease that can affect skin, nervous system, heart and joints. Lyme arthritis can develope in about 60% of "not treated" Lyme disease patients, 10% of patients may develope chronic arthritis. Lyme arhritis symptoms (especially chronic arthritis) is similar to rheumatoid arthritis. The purpose of this study was to establish the usefulness of examinations of serum levels of matrix metalloproteinases MMP-3, MMP-9, tissue inhibitor of metalloproteinases 1 (TIMP-1), hialuronic acid (HA) and antibodies against cyclic citrullinated peptide (anti-CCP) in Lyme arthritis, rheumatoid arthritis (RA) and patients with arthritic complaints. Plasma levels of MMP-3, HA and anti-CCP were significantly higher in RA group than in Lyme arthritis group and patients with arthritic complaints. There were no significant differences in serum levels of MMP-3, MMP-9, TIMP-1, HA, anti-CCP between Lyme arthritis patients and patients with arthritic complaints and these parameters are not usefull in differential diagnoses of Lyme arthritis. PMID- 22320033 TI - [Transverse myelitis]. AB - Transverse myelitis is a disease with various pathogenesis. It leads to a partial or total transverse lesion of the spinal cord structures resulting in an acute or subacute: motor (paralysis or paresis), sensory (most often with sensory level) and autonomic symptoms and signs. Its etiology is complex and sometimes difficult to establish explicitly. The most frequent reason of transverse myelitis is infection, but there are other factors like: postinfectious, neoplastic, paraneoplastic, demyelinating, immunological (connective tissue diseases), vascular and others. Idiopathic transverse myelitis accounts for about 10-40% of cases, and despite thorough diagnostics its aetiology cannot be established. Transeverse myelitis has been known for years, but it still poses a big problem both diagnostically and therapeuthically. Its course is frequently serious leading to persistent neurological damage and permanent disability. Diagnostic methods of choice are spinal cord MRI and CSF examination with assessment of oligoclonal bands, biomarkers of inflammatory process, 14-3-3 protein and neuronal specific enolase. Its treatment is determined by established aetiology. Many inconsistencies, no clear cut definition of the disease and lack of diagnostic criteria are being discussed by the group of experts working in Transverse Myelitis Consortium Group. PMID- 22320034 TI - [Invasive meningococcal disease--management and treatment]. AB - Invasive meningococcal disease is life threatening disease and in fulminant cases mortality rate may be as high as 70%. Rapid introduction of treatment and monitoring on intensive care unit is crucial for prognosis. The understanding of patomechanism responsible for sepsis development allow to introduce supportive treatment including glicocorticoids and recombinant human activated protein C. Very important is suitable prophylaxis among risk groups with, additional considering vaccination in the case of infection caused by A, C, Y, W-135 serogroups. PMID- 22320035 TI - [Antibiotic treatment in Lyme arthritis]. AB - Primary cause of Lyme arthritis (LA) is an invasion and survival of Borrelia burgdorferi s.l. spirochetes within joint tissues. Elimination of the pathogen is an effective treatment method in a great majority of patients and can be achieved by a number of antibiotic regimens of confirmed efficacy. Antibiotic therapy lasting for 2 to 4 weeks enables eradication of the infection, followed by resolution of arthritis within weeks to months. If insufficient, the course of therapy may be repeated up to 3 times in a few months' intervals, although effectiveness of repeated treatment is not so well confirmed and probably small. Further symptoms, persisting in spite of proper antibiotherapy, typically are not caused by ongoing infection, but rather by autoimmune phenomena or persistent damage to the joint, so further administration of antibiotics in such patients seems of no benefit. PMID- 22320036 TI - [Sepsis--perspectives regarding its prophylaxis, diagnosis and treatment]. AB - Actual criteria for diagnosis and classification of sepsis are presented, and the influence of an ongoing investigation of the pathogenesis of sepsis on the development of new diagnostic and therapeutic tools is discussed. Direct intervention in the innate immunity and systemic inflammatory response mechanisms seems promising therapeutic approach and some potential therapies are under development, including attempts to modulate function of innate immunity Toll-like receptors. PMID- 22320037 TI - [Seronegative Lyme arthritis]. AB - Serologic confirmation is required for diagnosis of Lyme borreliosis in all the patients except those with well confirmed and typical erythema migrans (EM) lesion. In patients with articular symptoms, the primary cause of seronegativity is performing a test at a very early stage of the disease, before detectable levels of anti-Borrelia burgdorferi s.l. antibodies build up. However, recent epidemiologic history and presence of primary skin lesion facilitate diagnosis in most patients at this stage of the infection. Secondly, insufficient antibiotic treatment of EM may halt development of humoral response without total eradication of the pathogen, which may result in the relapse of arthritis without detectable anti-B. burgdorferi s.l. antibodies for up to several months later--a rather rare phenomenon, which, however, must be taken into consideration in patients with a history of treated EM. A fe cases of seronegative Lyme arthritis not related to previous antibiotherapy have been reported, but i seems an extremely rare condition, and, if suspected, should be confirmed by histopathologic or molecular examination of the material from the affected joint. PMID- 22320038 TI - [Helicobacter pylori genome alleles S1 and S2 and morphological changes gastric mucosa in children and adults in the Bialystok province]. AB - Bacteria virulent proteins, among other vacA, have a significant role in the occurrence of gastric mucositis. AIM: The aim of the study was the evaluation of occurrence rate of alleles s1 and s2 of Helicobacter pylori vacA genome in children and adults, inhabitants of the Podlasie province. It was also to determine the correlation between infection with a determined s1 or s2 vacA genotype of the bacterium and the degree of severity and activity of antral mucositis. METHODS: 68-H. pylori infected persons (38 children and 30 adults) were examined, vacA genotypes of 70 H. pylori strain were evaluated. RESULTS: The degree of inflammatory changes in antral mucosa was differentiated and depended on vacA alleles of H. pylori strain. Allele s1 more frequently coexisted with moderate and severe antral mucositis in adults than in children (56.3% vs 50,0%, respectively). Allele s1 occurrence correlated with high activity inflammation in 47.5% of cases, medium activity--18.6%, and low activity--5.1%. CONCLUSIONS: Allele s1 was more frequently stated both in children and adults (86.8% and 81.3%, respectively) as compared to allele s2. Allele s1 also more frequently coexisted with low-activity inflammation or with no-activity inflammation of antral mucositis in children than in adults (36.8% vs 18.8%, respectively). PMID- 22320039 TI - [Clinical manifestation of Lyme borreliosis in children with positive and negatiwe western blot results]. AB - BACKGROUND: In the afforested area of North-Eastern Poland the risk of Borrelia burgdorferi infection seems to be higher compared to the other regions. Because of unspecific clinical manifestation of Lyme borreliosis in children the positive ELISA IgM results should be confirmed with Western blot IgM tests. OBJECTIVE: Retrospective analysis of clinical signs and symptoms of Lyme borreliosis in children with positive ELISA IgM and positive Western blot IgM results and in children with positive ELISA IgM and negative Western blot IgM results. MATERIAL AND METHODS: The study included 20 children reactive with ELISA IgM (Bellco Biomedica, Austria), hospitalized in Pediatric Infectious Diseases Clinic in 2007 due to probable diagnosis of Lyme disease. All children were tested with B. burgdorferi Western blot IgM and/or IgG assay (DRG, Diagnostics, Germany) as a second-step diagnosis. In 10 (50% females, 50% males) out of 20 children the results were positive (borreliosis) and in other 10 (80% females, 20% males) the results were negative (controls). In both groups of patients the retrospective analysis of signs and symptoms was done. RESULTS: The most often clinical manifestation of Lyme borreliosis in children was neuroborreliosis. Children presented Lyme meningitis (30%), facial nerve palsy (10%) and chronic or recurrent headaches (40%), associated with vertigo (20%), weakness (30%), fever (40%), and fatigue syndrome (30%). One patient presented Lyme arthritis. Children of control group presented with unspecific symptoms like isolated headaches (40%), arthralgias (70%), myalgias (10%) and abdomen pain (20%) CONCLUSIONS: (1) The most frequent clinical presentation of Lyme borreliosis in analyzed children was neuroborreliosis; (2) Isolated arthralgias in children reactive with B. burgdorferi ELISA IgM need to be confirmed with Western blot assay before implementing the antibiotic therapy. PMID- 22320040 TI - [The significance of immunoblot tests in diagnosis of Lyme borreliosis in children]. AB - OBJECTIVE: Verification of Lyme disease serodiagnosis in children by use of Western blot (WB) testing. MATERIAL AND METHODS: 24 children (8 males, 16 females) at the average age of 15,5y have been diagnosed from January 1st till December 31, 2007. All Lyme patients with positive or equivocal ELISA IgM and or ELISA IgG test results were included in the study. The ELISA (Bellco Biomedica, Austria)-Western blot (DRG, Diagnostics, Germany) two test protocol using sera of Lyme borreliosis patients was evaluated. RESULTS: Positive ELISA IgM results were confirmed in 20 out of 24 children (83,3%). In WB confirmation test, the positive results were obtained in 10 children (41,7%), equivocal results--in 22 (8.3%) and negative in 12 (50%) children. The quantitative accordance of both ELISA IgM-WB IgM tests was 50%. The higher quantitative accordance (96%) of both tests was obtained studying IgG serologic response. CONCLUSION: A positive ELISA IgM result very likely represents a false-positive result and should always be confirmed by WB assay and objective clinical signs of borreliosis before implementing the appropriate antimicrobial therapy. PMID- 22320041 TI - [Anti Yersinia enterocolitica antybodies titer in serum in patients with chronic Lyme arthritis]. AB - Yersiniosis is an acute infectious disease, which course may differ in dependence to age at which patient was infected. It may cause reactive arthritis in adults and seldom in children. The aim of the study was evaluation of anti Yersinia enterocolitica antibodies titer in group of patients with previously diagnosed Lyme disease. The subject of the study was group of 76 males, foresters from north-eastern Poland at the age of 26 to 60 years (x = 41), with long term history of Lyme disease. In 10% of examined patients positive anti Yersinia enterocolitica antibodies titer was observed. PMID- 22320042 TI - [Serum and cerebrospinal fluid concentration of vitamins A, E and C in patients with tick-borne encephalitis]. AB - We included in our study 18 patients hospitalized because of tick borne encephalitis (tbc) at the Departament of Infectious Diseases and Neuroinfections of Medical University of Bialystok. In this group, concentration of vitamins A, E and C in serum and cerebrospinal fluid (CSF) was measured before and after treatment. The control group consisted of 11 patients with no inflammatory changes in CSF were observed. We did not observe significant differences in concentration of vitamins in serum and CSF before and after treatment comparing to controls. However, we showed significant increase in concentration of vitamin E before and after treatment in both serum and CSF in patients with tbc in comparison with control group. PMID- 22320043 TI - [Molecular diagnostics of Babesia and Theileria]. AB - Protozoa Babesia and Theileria are a group of parasites transmitted by ticks and invading mammals' blood cells. Infections by these protozoa cause heavy losses among farm animals. Since human babesiosis was described forty years ago, the number of reported cases has been increasing. Conventional methods of parasitological diagnostics are unreliable in these diseases, especially in stages with low parasitemia. Methods of nucleic acids detection have been developing fast in recent years and are more and more specific and sensitive. Polymerase Chain Reaction (PCR) enables detection of DNA of Babesia and Theileria, even in parasitemia as low as a few organisms per milliliter. Real time PCR is useful especially in early stage of babesiosis when results of serological tests are negative and the blood smear does not reveal the pathogen or for distinction between intererythrocytic forms and Plasmodium. RLB is a method more sensitive than PCR and enabling detection of coinfections with different organisms. LAMB is a method of DNA amplification in isothermal conditions, offered as faster, easier, but still highly specific alternative to PCR. NASBA is a method where RNA of Babesia and Theileria is an initial template. The choice of a specific method highly depends on cost of laboratory equipment needed. PMID- 22320044 TI - [Favourable course of herpes simplex encephalitis in the 37-year-old woman in 26th weeks of pregnancy]. AB - Herpes simplex (HSV) encephalitis is a disease with a high mortality. HSV infections affect relatively young people. Characteristic neurological signs, MRI findings, PCR of cerebrospinal fluid (CSF) are useful tools in early recognition of HSV encephalitis. We present a case of HSV encephalitis with favourable course in 37-year-old woman in 26 week of pregnancy. PMID- 22320045 TI - [Ecologic study of the risk of tick-borne encephalitis in Poland--presentation of the method]. AB - Currently an ecologic study assessing the relationship between tick-borne encephalitis (TBE) with diverse environmental and social factors at the lowest administrative level is developed for Poland. Because the disease is affecting only part of the country, the authors will try to identify factors which could explain this uneven geographic distribution of the disease. To increase precision of the analysis we will utilize the highest possible resolution of the analysis, for which routinely collected data are available. Part of the data at the commune level will be obtained from the Polish communicable disease surveillance system and the Central Statistical Office, and part will be obtained using GIS tools from maps prepared by diverse institutions. The outcome studied will be TBE cases assigned to commune of residence or to place of exposure. The explanatory variables will be: land use categories (percent of commune area and their border length), meteorological variables (temperatures, rainfall), socio-economic status of communes (income per capita, unemployment rate), and Lyme borreliosis incidence (as a complex indicator of tick activity and human to tick exposure). PMID- 22320046 TI - [The spinal epidural abscess effective conservative treatment]. AB - We present a case of 61-years-old man admitted to our department because of a strong pain in lumbar area and lower extremities. There was no neurological deficit in physical examination. MRI showed multiple extradural abscesses in thoracic and lumbar spine. Patient was treated with intravenous antibiotics and intraspinal immunoglobulin infusions. We observed gradual improvement of patient's condition, with resolution of fever and pain. PMID- 22320047 TI - [Estimation of brain atrophic processes among patients with past history of TBE (with EEG evaluation)]. AB - The aim of the study was estimation of brain atrophic processes among patients with past history long lasting, or encephalitic course (8-10 years after) TBE with using planimetric measurements of CT scans in connection with EEG evaluation. 34 patients were enrolled to the study. First results suggest the presence of sequel past TBE as increased percentage pathology in EEG evaluation as well increasing of anterior horns lateral ventricules, dilatation the III ventricule as a result of fastened brain atrophy in relation to the age of the patients. PMID- 22320048 TI - [Underestimated problem of Chlamydia infections]. AB - Microorganisms which belong to Chlamydophila sp and Chlamydia sp genus are intracellular pathogens with characteristic life cycle. In humans the most common infections are caused by Chlamydophila pneumoniae i Chlamydia trachomatis.These pathogens are mainly responsible for infections of upper respiratory tract, infections of urinary tract and conjunctivitis. They are also considered to take part in patophysiology of Atherosclerosis, nervous system diseases and exacerbation of chronic respiratory tract diseases. PMID- 22320049 TI - [Lyme borreliosis--guidelines of treatment and expectations of patients]. AB - Clinical and patophysiological aspects of Lyme borreliosis influencing effectives of treatments are introduced. European recommendations--results of EUCALB export group (regarding European multistrains specificity), AAN-American Academy Neurology as well ILADS Working Group based on experience from North America supported of some important studies connected with duration of therapy are described. Expectations of patients are introduced. PMID- 22320050 TI - [Examination of intrathecal immunological response to Borrelia burgdorferi antigens in patients with suspected neuroborreliosis--a preliminary communication]. AB - 10 persons with suspected neuroborreliosis (in accordance with EUCALB recommendations), inpatients of Departament of Infectious Diseases and Neuroinfections were evaluated. Antibodies of IgM and IgG in CSF and serum against B. burgdorferi were tested with Western blot kits (Mikrogen, Germany). 3 of 10 tested CSF showed presence of additional bands in comparison with serum. Simultanously evaluation antibodies against B. burgdorferi in CSF and serum with Western blot kits patients with suspected neuroborreliosis is usefull to estimate intrathecal immunological response, with showing the differences between CSF and serum. Estimation of immunological response is Essentials in both classes especially in Elary phase of disease. PMID- 22320051 TI - [Encephalomeningitis caused by Listeria monocytogenes in patient infected by TBE virus--case report]. AB - The epidemiology of listeriosis is constantly changing towards higher incidence. The most endangered group of patients are people with immunodeficiency caused by coexisting diseases. In these cases listeriosis may take a very severe course. In this paper we present a case of a 76 year old female who suffered from encephalomeningitis caused by Listeria monocytogenes and additionally was infected by tick borne encephalitis virus and Borrelia burgdorferi. PMID- 22320052 TI - Mass-spring-damper modelling of the human body to study running and hopping--an overview. AB - Several mass-spring-damper models have been developed to study the response of the human body to the collision with the ground during hopping, trotting, or running. The mass, spring, and damper elements represent the masses, stiffness properties, and damping properties of hard and soft tissues. The masses that models are composed of are connected to each other via springs and dampers. The present paper reviews the various types of mass-spring-damper models including one-body and multi-body models. The models are further categorized as being either passive or active. In passive models, the mechanical properties (stiffness and damping) of soft tissues remain constant regardless of the type of footwear, ground stiffness, etc. In active models, the mechanical properties adapt to external loads. The governing equations of motion of all models as well as their parameters are presented. The specific ways that the models take account of the shoe-ground interactions are discussed as well. The methods used for determination of different modelling parameters are briefly surveyed. The advantages and disadvantages of the different types of mass-spring-damper models are also discussed. The paper concludes with a brief discussion of possible future research trends in the area of mass-spring-damper modelling. PMID- 22320053 TI - Future trends in the use of X-ray fluoroscopy for the measurement and modelling of joint motion. AB - Knowledge of three-dimensional skeletal kinematics during functional activities such as walking, is required for accurate modelling of joint motion and loading, and is important in identifying the effects of injury and disease. For example, accurate measurement of joint kinematics is essential in understanding the pathogenesis of osteoarthritis and its symptoms and for developing strategies to alleviate joint pain. Bi-plane X-ray fluoroscopy has the capacity to accurately and non-invasively measure human joint motion in vivo. Joint kinematics obtained using bi-plane X-ray fluoroscopy will aid in the development of more complex musculoskeletal models, which may be used to assess joint function and disease and plan surgical interventions and post-operative rehabilitation strategies. At present, however, commercial C-arm systems constrain the motion of the subject within the imaging field of view, thus precluding recording of motions such as overground gait. These fluoroscopy systems also operate at low frame rates and therefore cannot accurately capture high-speed joint motion during tasks such as running and throwing. In the future, bi-plane fluoroscopy systems may include computer-controlled tracking for the measurement of joint kinematics over entire cycles of overground gait without constraining motion of the subject. High-speed cameras will facilitate measurement of high-impulse joint motions, and computationally efficient pose-estimation software may provide a fast and fully automated process for quantification of natural joint motion. PMID- 22320054 TI - A cost-effective extracorporeal magnetically-levitated centrifugal blood pump employing a disposable magnet-free impeller. AB - In the field of rotary blood pumps, contactless support of the impeller by a magnetic bearing has been identified as a promising method to reduce blood damage and enhance durability. The authors developed a two-degrees-of-freedom radial controlled magnetic bearing system without a permanent magnet in the impeller in order that a low-cost disposable pump-head for an extracorporeal centrifugal blood pump could be manufactured more easily. Stable levitation and contactless rotation of the 'magnet-free' impeller were realized for a prototype blood-pump that made use of this magnetic bearing. The run-out of the impeller position at between 1000 r/min and 3000 r/min was less than 40 microm in the radial controlled directions. The total power consumption of the magnetic bearing was less than 1 W at the same rotational speeds. When the pump was operated, a flow rate of 5 l/min against a head pressure of 78.66 kPa was achieved at a rotational speed of 4000 r/min, which is sufficient for extracorporeal circulation support. The proposed technology offers the advantage of low-cost mass production of disposable pump heads. PMID- 22320055 TI - Two-dimensional finite element simulation of fracture and fatigue behaviours of alumina microstructures for hip prosthesis. AB - This paper describes a two-dimensional (2D) finite element simulation for fracture and fatigue behaviours of pure alumina microstructures such as those found at hip prostheses. Finite element models are developed using actual Al2O3 microstructures and a bilinear cohesive zone law. Simulation conditions are similar to those found at a slip zone in a dry contact between a femoral head and an acetabular cup of hip prosthesis. Contact stresses are imposed to generate cracks in the models. Magnitudes of imposed stresses are higher than those found at the microscopic scale. Effects of microstructures and contact stresses are investigated in terms of crack formation. In addition, fatigue behaviour of the microstructure is determined by performing simulations under cyclic loading conditions. It is shown that crack density observed in a microstructure increases with increasing magnitude of applied contact stress. Moreover, crack density increases linearly with respect to the number of fatigue cycles within a given contact stress range. Meanwhile, as applied contact stress increases, number of cycles to failure decreases gradually. Finally, this proposed finite element simulation offers an effective method for identifying fracture and fatigue behaviours of a microstructure provided that microstructure images are available. PMID- 22320056 TI - Mechanical characterization of fourth generation composite humerus. AB - Mechanical data on upper extremity surrogate bones, supporting use as biomechanical tools, is limited. The objective of this study was to characterize the structural behaviour of the fourth-generation composite humerus under simulated physiologic bending, specifically, stiffness, rigidity, and mid diaphysial surface strains. Three humeri were tested in four-point bending, in anatomically defined anteroposterior (AP) and mediolateral (ML) planes. Stiffness and rigidity were derived using load-displacement data. Principal strains were determined at the anterior, posterior, medial, and lateral surfaces in the humeral mid-diaphysial transverse plane of one specimen using stacked rosettes. Linear structural behaviour was observed within the test range. Average stiffness and rigidity were greater in the ML (918 +/- 18 N/mm; 98.4 +/- 1.9 Nm2) than the AP plane (833 +/- 16 N/mm; 89.3 +/- 1.6 Nm2), with little inter-specimen variability. The ML/AP rigidity ratio was 1.1. Surface principal strains were similar at the anterior (5.41 micro epsilon/N) and posterior (5.43 micro epsilon/N) gauges for AP bending, and comparatively less for ML bending, i.e. 5.1 and 4.5 micro epsilon/N, at the medial and lateral gauges, respectively. This study provides novel strain and stiffness data for the fourth-generation composite humerus and also adds to published construct rigidity data. The presented results support the use of this composite bone as a tool for modelling and experimentation. PMID- 22320057 TI - Kinematic modelling of a robotic gait device for early rehabilitation of walking. AB - Rehabilitation of walking is an essential element in the treatment of incomplete spinal cord injured (SCI) patients. During the early post injury period, patients find it challenging to practice upright walking. Simulating stepping movements in a supine posture may be easier and promote earlier rehabilitation. A robotic orthotic device for early intervention in spinal cord injury that does not require the patient to be in an upright posture has been modelled. The model comprises a two-bar mechanical system that is configured and powered to provide limb kinematics that approximate normal overground walking. The modelling work has been based on gait analysis performed on healthy subjects walking at 50 per cent, 75 per cent, and 100 per cent of normal cadence. Simulated angles of hip, knee, and ankle joints show a comparable range of motion (ROM) to the experimental walking data measured in healthy subjects. The model provides operating parameters for a prospective recumbent gait orthosis that could be used in early walking rehabilitation of incomplete SCI patients. PMID- 22320058 TI - A preliminary dual-energy X-ray absorptiometry-based finite element model for assessing osteoporotic hip fracture risk. AB - To more accurately assess osteoporotic hip fracture risk in a specific patient, a dual-energy X-ray absorptiometry (DXA)-based finite element model was constructed from the patient's femur DXA image. The outermost contour of the femur bone segmented from the DXA image was used to generate a finite element mesh. Bone mechanical properties, such as Young's modulus, are correlated with areal bone mineral density (BMD) captured in the DXA image. A quasi-static loading condition representing a sideway fall was applied to the finite element model. Three fracture risk indices were introduced and expressed as ratios of internal forces caused by impact forces occurring in sideway fall to bone ultimate cross-section strength at the three critical locations, i.e. the femoral neck, the intertrochanteric region, and the subtrochanteric region. The proposed finite element modelling procedure was validated against six representative clinical cases extracted from the Manitoba BMD database, where initial and follow-up DXA images have been taken to monitor longitudinal variation of areal BMD in individual patients. It was found from the clinical validation that variations in the proposed fracture risk indices have the same trends as those indicated by the conventional areal BMD and T-score. In addition, by the three proposed fracture risk indices it is possible to further identify the specific fracture location. It was also found that for the same subject, the variations in the three fracture risk indices have quite different magnitudes, with intertrochanteric region the largest and subtrochanteric region the smallest, which is probably owing to the different content of trabecular and cortical bones in the three regions. With further development, it is promising that the proposed DXA-based finite element model will be a useful tool for accurate assessment of osteoporosis development and for treatment monitoring. PMID- 22320059 TI - Concept for a gas-cell-driven drug delivery system for therapeutic applications. AB - This paper presents a concept for an implantable micro-pump based on hydrogen generating gas cells. The gas-generating cell is separated from the drug reservoir by an expandable latex membrane. The system offers linear drug delivery with flowrates ranging from 8 nl/s to 2 microl/s and a total delivery volume of up to 160 ml. Drugs can be dispensed over a wide backpressure range. The device is scalable based on the size of the gas-producing cell and requires no external energy source. Possible fields of application include in vivo local drug delivery for chemotherapy, diabetes, and pain management. PMID- 22320060 TI - Early childhood caries: a complex problem requiring a complex intervention. PMID- 22320061 TI - Why has oral health promotion and prevention failed children requiring general anaesthesia for dental extractions? AB - OBJECTIVES: Many children in the UK still require dental treatment under general anaesthesia (DGA). Why oral health promotion and prevention, in this cohort of children, has failed is poorly understood. By questioning the parents/carers of children undergoing DGA this study aimed to establish: 1 previous exposure to oral health education and promotion activities; 2 beliefs and behaviours about dental caries and prevention; and 3 what parents perceive useful in preventing dental caries. BASIC RESEARCH DESIGN: A cross-sectional questionnaire based study. CLINICAL SETTING: Dental general anaesthetic centres in Wales, UK. PARTICIPANTS: 207 consecutively attending parents of children aged < 10 years requiring a DGA. RESULTS: In total, 150 (76%) parents/carers claimed to have received previous oral health advice and 103 (52%) had received toothbrushing instruction from a dentist. Only 18 (9%) reported the application of topical fluoride. Sixty seven (34%) believed "tooth decay runs in families" and 53 (27%) it was simply bad luck that their child had dental decay. The majority (89%) believed that information leaflets on oral health would be useful and 133 (67%) would find information on a website helpful. CONCLUSIONS: This study suggests that there is a significant scope for increasing the exposure of high risk children to fluoride. A sense of fatalism and erroneous beliefs were evident amongst some parents/carers of children needing DGA. These issues need to be addressed in the future design of oral health promotion/prevention activities. PMID- 22320062 TI - The relationship between dental care and perceived oral health impacts. AB - BACKGROUND: Knowledge of the effect of dental care and dental visiting behavior on oral health impacts is important for effective resource allocation. OBJECTIVE: To determine the association between dental care, including the reason for dental attendance and time since last dental visit, with perceived oral health impacts among Australian adults. METHODS: Data were obtained from the Australian National Survey of Adult Oral Health 2004/06. Analysis was limited to 4,170 dentate adults who answered the Oral Health Impact Profile (OHIP-14) questions. Prevalence of frequent impacts was defined as the percentage of people reporting 'fairly often' or 'very often' to one or more of the OHIP-14 questions. RESULTS: Over half the dentate Australians (63.0%) visited a dentist in the past year. Unadjusted analysis showed a statistically significant association between the prevalence of frequent impacts and receipt of: extractions (prevalence ratio = 1.7, 95% CI = 1.2-2.2), scale/clean (0.7, 0.5-0.8), and denture care (1.6, 1.1-2.4). After adjustment for the usual reason for dental attendance there was no effect of any of the three treatments or the time since last visit on the prevalence of frequent impacts. CONCLUSION: The usual reason for dental attendance, and not the time since last visit or the type of dental care supplied, accounted for differences in perceived oral health impacts. PMID- 22320063 TI - Is the shortened dental arch an underused treatment strategy in the Republic of Ireland? AB - OBJECTIVES: To determine the proportion of Republic of Ireland 35-44 and 65+ year olds currently satisfying the criteria for a classic shortened dental arch (SDA) of 20 anterior teeth. RESEARCH DESIGN: Secondary analysis of data collected in the 2000/02 epidemiological survey of the oral health of Irish adults. CLINICAL SETTING: Participants underwent a clinical oral examination in health board dental clinics and completed a detailed interview pertaining to dental and general health. PARTICIPANTS: The analysis is based on a random sample of adults, aged 35 to 44 years (n = 978), and 65 years and older (n = 714). MAIN OUTCOME MEASURES: The SDA was measured as 20 teeth in the mouth in the positions normally described as from the left second premolar to the right second premolar in each arch. RESULTS: Only one of the 35-44 year-olds and none of the 65+ year-olds had teeth in their mouths in positions normally described as a classic SDA. However, of the 35-44 year old age group only five patients who had at least a premolar dentition of 20 contiguous teeth had been provided with a removable denture compared to one patient from the 65+ years group. CONCLUSIONS: Very few older patients in the Republic of Ireland have a SDA based on the measure used. However, very few have been provided with removable dentures where they already possess at least a premolar dentition of 20 contiguous teeth. Suggested reasons for this may include limitations of the data recorded, patient preferences and economic factors. PMID- 22320064 TI - Predictors of utilisation of dental care services in a nationally representative sample of adults. AB - OBJECTIVE: The objective of this study was to identify the predictors of utilisation of dental care services in Ireland. PARTICIPANTS: The 2007 Irish Survey of Lifestyle, Attitudes and Nutrition is a cross-sectional study, conducted in 2006/2007 (n = 10,364), by interviews at home to a representative sample of adults aged 18 years or over. MAIN OUTCOME MEASURES: Multivariate logistic regression was used to investigate the influence of socioeconomic, predisposing and enabling factors on the odds of males and females having a dental visit in the past year. RESULTS: The significant predictors of visiting the dentist in the past year were for males: having 3rd level education, employment status, earning 50,000 euros or more, location of residence, use of a car, brushing frequently, and dentition status. For females, the predictors were being between 25-34 or 55-64 years-old, education level, earning 50,000 euros or more, location of residence, use of a car, brushing frequently and dentition status. CONCLUSIONS: Predictors of the use of dental services vary by gender. Predictors common to both genders were education level, higher income, location of residence, use of a car, brushing frequently and dentition status. Many of the predictors of dental visiting in the past year are also related to social inequalities in health. These predictors may be useful markers of impact for policies designed to address inequalities in access to oral health services. PMID- 22320065 TI - Applicability of both dentist and patient perceptions of dentists' explanations to the evaluation of dentist-patient communication. AB - OBJECTIVES: Very little is known about dentist-patient communicative behaviours in actual practice. This study evaluated dentist and patient perceptions of dentist-patient communication and patient outcome. PARTICIPANTS: The subjects were 171 dentist-patient pairs in Kitakyushu, Japan. RESEARCH DESIGN: Dentists and patients answered the same questionnaire items using the same response categories to evaluate dentist-patient communication. Based on the scores of patient and dentist perceptions with respect to dentist-patient communication, patient-dentist pairs were categorised into one of 3 groups. Data analyses used one-way ANOVA, multiple linear regression analysis, and multiple logistic regression analysis. RESULTS: We found that, with respect to dentist-patient communication, patients in the 'patient better' group (i.e., the patient's evaluation was more positive than the dentist's evaluation) were more likely to have a positive outcome (e.g., 'improvement of health and fear,' 'satisfaction with care') than those in the other two groups. Patients in the 'doctor better' group (i.e., the dentist's evaluation was the more positive) were more likely to have a negative outcome than those in the other two groups. CONCLUSIONS: A positive patient outcome is more likely when the patient's evaluation is better than a dentist's evaluation with respect to dentist-patient communicative behaviours. The method based on patient and dentist perceptions with respect to dentist-patient communication might be effective in evaluating dentist-patient communication. PMID- 22320066 TI - Oral health behaviour of urban and semi-urban schoolchildren in the Lao PDR. AB - OBJECTIVE: To describe the oral health related knowledge, behaviour, and attitude towards health of 12-year old Lao schoolchildren; analyse how health risk factors relate to socio-demographic background; and determine the relative effect of living conditions on health and risk behaviour. METHODS: Cross sectional study of 12-year old schoolchildren chosen by multistage sampling to fit the objective of the study. The final sample comprised 621 children of 2nd grade of secondary schools in Vientiane, Lao Peoples Democratic Republic. Data were collected by structured questionnaire covering behaviour, attitudes and knowledge related to oral and general health and perception of own health. RESULTS: 69% of the children reported toothache during the previous 12 months and 38% reported school absenteeism due to toothache. Nevertheless, 77% stated frequent brushing and 91% the use of fluoridated toothpaste. Only 29% reported dental visits for this period while 42% had never seen a dentist. Fear of pain, cost and distance were stated as barriers for dental visits. Knowledge on caries prevention was high, aetiology of oral disease less known, and intake of hidden sugar surprisingly frequent. Socio-economic position and attitude towards health were important predictors for oral health behaviour and risk behaviour. CONCLUSIONS: Despite regular tooth brushing practice and widespread use of fluoridated toothpaste school absenteeism due to toothache is high. Significant socio-demographic gradient exists in risk factors for oral health. To reduce oral health inequality systematic oral health promotion should be implemented through the existing school health platform strengthening healthy behaviour and focussing on risk factors for oral as well as general health. PMID- 22320067 TI - Evaluation of a preventive program based on caries risk among mentally challenged children using the Cariogram model. AB - OBJECTIVES: To assess the caries risk and to evaluate the risk based preventive program at the end of 10 months amongst the mentally challenged children using the Cariogram model. BASIC RESEARCH DESIGN: Longitudinal field trial with before and after comparison. PARTICIPANTS: 54 children (7-17years old) with mild to severe mental disability constituted the study sample. CLINICAL SETTING: Brahmadutta School, for the mentally challenged children situated in Pimpri (Maharashtra) India. INTERVENTIONS: Phase I: Information of the Cariogram parameters (caries experience, diet content, diet frequency, plaque amount, mutans streptococci, fluoride program, saliva secretion and saliva buffer capacity) were collected, which were used to generate the individual caries profile, based on which the children were divided into 5 risk groups. Phase II: Risk based preventive program was implemented. Phase III: At the end of 10 months, caries profile was generated again. MAIN OUTCOME MEASURES: The effectiveness of the preventive program was assessed by comparing the baseline and follow-up caries profile. Wilcoxon Signed Ranks test was used for statistical analysis. RESULTS: As compared to the baseline, there was a 57% increase in the number of children in "low caries risk group" and for the caries risk factors diet content, diet frequency, plaque amount and Mutans streptococci count had significantly lower values. At follow-up, only 4 new carious lesions developed. CONCLUSION: The preventive program was effective in improving the caries risk factors and increasing the "chance to avoid caries" from a mean of 44% to 87%. PMID- 22320068 TI - The effect of a modified fluoride toothpaste technique on buccal enamel caries in adults with high caries prevalence: a 2-year clinical trial. AB - OBJECTIVE: To evaluate the preventive effect of a "modified fluoride (F) toothpaste technique" on the incidence and progression of buccal/ lingual enamel caries among Saudi adults with high caries prevalence. METHOD: Adults were randomly assigned to test and control groups. Test group patients were instructed to use the provided F toothpaste twice a day as follows: 1, use 2cm toothpaste; 2, brush for 2 min; 3, swish the toothpaste slurry around the teeth for about half a minute before spitting it out; and 4, no post-brushing water rinsing and no eating/drinking for 2hr. The patients in the control group (n = 57) were instructed to continue using their regular F toothpaste twice a day without any further instructions. The patients' compliance in the test group was assessed after 2 years. RESULTS: Of 175 adults, 113 completed the study. The test group (n = 56) had a lower enamel mean caries incidence 0.56 (sd 1.04) than the control group (n = 57), 1.01 (1.00) (p < 0.05), with a preventive fraction of 44%. There was no difference regarding enamel caries progression or arrested caries. The caries incidence in the test group was higher in the subgroup of patients who rinsed with water post-brushing and who only brushed once a day (p < 0.05). CONCLUSION: The "modified fluoride toothpaste technique", as practised over the 2 years in a Saudi population with high caries prevalence, had a preventive effect on the incidence of buccal/lingual enamel caries but not on the progression. PMID- 22320069 TI - Association of clinical oral health status with self-rated oral health and GOHAI in Japanese adults. AB - OBJECTIVE: The objective of this study was to investigate clinical oral health status relationships that affect quality of life (using the 12-item General Oral Health Assessment Index (GOHAI)) and self-rated oral health in a community of Japanese residents. METHODS: 459 residents of Yokote City, Japan aged 40-55 years had oral health examinations and completed self-administered questionnaires collecting data on age, gender, GOHAI items and self-rated oral health. Linear regression analysis was performed with GOHAI or self-rated oral health as a dependent variable and gender, age and indicators of oral health status as independent variables. RESULTS: The GOHAI indicated 42.7% of subjects were concerned about the appearance of their teeth, 30.1% were worried about teeth problems and 27.5% concerned about sensitive teeth. Analyses showed that gender, decayed teeth, oral dryness and missing teeth were significantly associated with variation in GOHAI scores, and that gender, decayed teeth, oral dryness and oral hygiene were significantly associated with variation in self-rated oral health. CONCLUSION: This study revealed that in this sample of Japanese adults aged 40-55 years, decayed teeth and oral dryness affected both GOHAI and self-rated oral health, whereas missing teeth affected GOHAI and oral hygiene affected self-rated oral health. Subjects did not recognise periodontal disease as a quality of life impacting condition or as a health problem. PMID- 22320070 TI - Prevalence of periodontopathogens in a black Brazilian secluded community matched with a black urban population. AB - OBJECTIVE: To evaluate the prevalence of periodontopathogens according to periodontal profile in a black Brazilian secluded community matched with an urban black population. PARTICIPANTS: A total of 84 subjects were selected, 42 (mean age 25.7 sd 18.0 years) from a secluded community called Santo Antonio do Guapore (SAG) and 42 (mean age 25.4 sd 18.1 years) from an urban area of Sao Paulo State (SPT). METHODS: Participants received clinical examinations as follows: periodontal pocket depth; clinical attachment loss; plaque and gingival indexes. After examination, the secluded population was classified as periodontal health (13), gingivitis (15) or periodontitis (14). Then, 182 urban volunteers were screened and 42 subjects were selected matched for the variables: periodontal diagnosis, age (+/- 2 years) and gender. Samples were taken for microbial analysis. Genomic DNA for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Campylobacter rectus, Tannerella forsythia and Prevotella intermedia was provided by polymerase chain reaction. RESULTS: Except for C. rectus, all pathogens were present in both groups with no statistically significant difference. In particular, C. rectus was more prevalent only in gingivitis subjects from the SPT group (p<0.05). A high frequency of periodontopathogens was related to the severity of periodontal disease. CONCLUSION: In general, the prevalence of the examined periodontopathogens in this study did not differ between a secluded black Brazilian population and an urban black population. PMID- 22320071 TI - Association of pulp stones with coronary artery stenosis. AB - BACKGROUND: Dental pulp stones are discrete calcifications in the pulp chamber which are often seen in deciduous and permanent teeth. It has been hypothesised that atherosclerosis can be associated with their development. OBJECTIVE: To determine whether a higher prevalence of dental pulp stones is correlated with coronary artery stenosis. CLINICAL SETTING: Sixty-one patients aged 20-55 years referred to Afshar Heart Center for invasive coronary angiography were invited to undergo panoramic dental radiography. The panoramic radiographs were independently examined for the presence of pulp stones. RESULTS: Pulp stones were present in 82% (31/38) of patients with at least one clinically significant coronary artery stenosis and in 48% (11/23) of patients with normal coronary angiography. They were present in 13% of the teeth in the former group and in 5% of the teeth in the latter. The findings show a statistically significant association between coronary artery stenosis and presence of pulp stones (odds ratio 4.83, 95% confidence interval 1.5-15.4). CONCLUSION: Coronary artery stenosis and dental pulp calcification are significantly associated. Dental radiography has the potential to be used as a rapid screening method for the early detection of coronary artery stenosis. PMID- 22320072 TI - Incisor trauma in a Turkish preschool population: prevalence and socio-economic risk factors. AB - OBJECTIVE: This study aimed to assess the prevalence of traumatic injuries of the primary incisors in preschool children from 2 to 5 years old in South-Eastern Anatolia, Turkey. Additionally, the relationship between traumatic dental injuries, parents' education level, family income, size of incisal overjet and the presence of anterior open bite were examined. BASIC RESEARCH DESIGN: A cross sectional survey CLINICAL SETTINGS: Data were collected through oral examinations and structured interviews, and included socio-economic indicators. PARTICIPANTS: A total of 727 children of both genders were included in the study. 122 of these children were aged 2; 183 aged 3; 178 aged 4 and 186 aged 5. RESULTS: The prevalence of dental injuries was 8.0% (n = 58). The highest frequency of trauma in the primary teeth was observed at the age of 4. Boys experienced more dental injuries than girls, 12.2% and 4.0%, respectively. The most common crown fracture was in enamel only (57%) followed by crown fracture of enamel and dentin (19%). CONCLUSION: The prevalence of dental injuries in Turkish preschool children was very low. The children with incisal overjet greater than 5mm and anterior open bite experienced more dental injuries in primary teeth than their counterparts with normal occlusion. Socio-economic indicators were not statistically significantly associated with the occurrence of traumatic dental injuries. PMID- 22320073 TI - Malocclusion and orthodontic treatment need measured by the dental aesthetic index and its association with dental caries in Indian schoolchildren. AB - OBJECTIVE: To assess prevalence of malocclusion and orthodontic treatment needs among 12 year old Indians using the Dental Aesthetic Index, and to find its association with dental caries. METHOD: 927 schoolchildren were randomly selected and their DAI and dentition status scores were recorded as per 1997 World Health Organization criteria. Clinical exams were carried out by one trained and calibrated examiner. The Chi-square test, Z-test and Spearman's correlation test were carried out. RESULTS: Mean DAI score was 19.2 (sd 6.8). Differences were found between male and female DAI scores (Z < or = 0.05). 82% of children had DAI scores < 26 with no or minor malocclusion requiring no or little treatment, 3.2% had DAI scores 31-35 with severe malocclusion requiring highly desirable treatment and 1.8% DAI scores > 35 with handicapping malocclusion requiring mandatory treatment. A mean DMFT of 1.15 (sd 1.62) was recorded. Severe and handicapping malocclusions were associated with dental caries. CONCLUSIONS: The distribution of DAI scores among Indian schoolchildren differs from that reported in other populations. Positive correlation was found between severe and handicapping malocclusion with dental caries. PMID- 22320074 TI - Nontarget screening methods for the analysis of contaminant residues in food matrixes by gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. PMID- 22320075 TI - Suitability of an orbitrap mass spectrometer for the screening of pesticide residues in extracts of fruits and vegetables. AB - For about 500 pesticides, the sensitivity of a benchtop high-resolution mass spectrometer using the Orbitrap for mass separation was compared to that of a widely used (low-resolution) tandem mass spectrometer. Both instruments were coupled to LC and used electrospray ionization. The selectivity of the Orbitrap in the full-scan acquisition mode without fragmentation was evaluated at a resolution of 100 000 full width at half maximum for all pesticides detectable with sufficient sensitivity. For this purpose, quasimolecular ions were extracted within 5 ppm windows from total ion chromatograms of two types of extracts of cucumber, lemon, wheat flour, raisin, and tea. In each of the obtained reconstructed ion chromatograms (individual chromatograms for 500 pesticides, each pesticide in 10 different extracts) the sum of signals not arising from the analyte was used to get a measure on selectivity. In addition, the target analyte list was checked for ions of similar mass. The influence of matrix on the ability to detect low concentrations of fortified pesticides was also studied, with the help of spiked extracts. This part of the survey tested whether analyte peaks were lost because of insufficient mass resolution or an early closing C-Trap (used to control the ion current into the Orbitrap). Finally, the stability of the ion ratio [M+H]+/[M+Na]+ was tested, which may be helpful to confirm the identity of an analyte. PMID- 22320076 TI - Evaluation of relevant time-of-flight-MS parameters used in HPLC/MS full-scan screening methods for pesticide residues. AB - An automatic screening method based on HPLC/time-of-flight (TOF)-MS (full scan) was used for the analysis of 103 non-European fruit and vegetable samples after extraction by the quick, easy, cheap, effective, rugged, and safe method. The screening method uses a database that includes 300 pesticides, their fragments, and isotopical signals (910 ions) that identified 210 pesticides in 78 positive samples, with the highest number of detection being nine pesticides/sample. The concentrations of 97 pesticides were <10 microg/kg, 53 were between 10 and 100 microg/kg, and 60 were at a concentration of >100 microg/kg. Several parameters of the automatic screening method were carefully studied to avoid false positives and negatives in the studied samples; these included peak filter (number of chromatographic peak counts) and search criteria (retention time and error window). These parameters were affected by differences in mass accuracy and sensitivity of the two HPLC/TOF-MS systems used with different resolution powers (15 000 and 7500), the capabilities of which for resolving the ions included in the database from the matrix ions were studied in four matrixes, viz., pepper, rice, garlic, and cauliflower. Both of these mass resolutions were found to be satisfactory to resolve interferences from the signals of interest in the studied matrixes. PMID- 22320077 TI - Applications of LC/ESI-MS/MS and UHPLC/Qq-TOF-MS for the determination of 141 pesticides in tea. AB - This paper presents the applications of LC-electrospray ionization (ESI)/MS/MS and ultra-HPLC (UHPLC)/ESI quadrupole (Qq)-time-of-flight (TOF) MS for the determination of 141 pesticides in tea. Pesticides were extracted and cleaned up from tea with a modified quick, easy, cheap, effective, rugged, and safe method using graphitized carbon black and primary-secondary amine sorbents. Quantification was achieved using matrix-matched standard calibration curves with isotopically labeled standards or a chemical analog as internal standards in an analytical range from 5 to 500 microg/kg. The LC/ESI-MS/MS served as a reliable tool to quantify the pesticides due to its superior sensitivity and good repeatability. Its method performance characteristics that include overall recovery, intermediate precision, and measurement uncertainty were evaluated according to a statistically designed experiment, i.e., a nested design. About 87% of the pesticides had recoveries between 81 and 110%; 94% had an intermediate precision < or = 20%; and 90% showed measurement uncertainty < or = 40%. About 92% of the pesticides were able to be detected at 5 microg/kg with an S/N > or = 3. The UHPLC/Qq-TOF-MS showed much less sensitivity and poorer repeatability compared to the LC/ESI-MS/MS, and, therefore, it was primarily used for confirmatory purposes based on the accurate mass measurement and isotopic patterns. PMID- 22320078 TI - Multiresidue analysis of plant growth regulators in grapes by triple quadrupole and quadrupole-time of flight-based liquid chromatography/mass spectrometry. AB - A selective and sensitive LC-MS/MS method is presented for simultaneous determination of 12 plant growth regulators, viz., indol-3-acetic acid, indol-3 butyric acid, kinetin, zeatin, 6-benzyl aminopurine, gibberellic acid, abscisic acid, chlormequat chloride, forchlorfenuron, paclobutrazole, daminozide, and 2,4 dichlorophenoxy acetic acid, in bud sprouts and grape berries. The sample preparation method involved extraction of homogenized sample (5 g) with 40 mL methanol (80%), and final determination was by LC-MS/MS in the multiple reaction monitoring (MRM) mode with time segmentation for quantification supported by complementary analysis by quadrupole-time of flight (Q-TOF) MS with targeted high resolution MS/MS scanning for confirmatory identification based on accurate mass measurements. The recovery of the test compounds ranged within 90-107% with precision RSD less than 5% (n = 6). The method could be successfully applied in analyzing incurred residue samples, and the strength of accurate mass analysis could be utilized in identifying the compounds in cases where the qualifier MRM ions were absent or at an S/N less than 3:1 due to low concentrations. PMID- 22320079 TI - Validation of automated library-based qualitative screening of pesticides by comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry. AB - A method for automated detection and reporting of pesticides in plant materials based on comprehensive two-dimensional GC/time-of-flight MS with library-based detection by software has been developed and validated. Optimum settings for detection parameters such as spectral match threshold and first and second dimension retention time tolerances were assessed with respect to occurrence of false detects and false negatives. Next the method was validated following European Union guidelines established for qualitative screening of pesticides. The validation was largely done in retrospect by using data obtained for spiked samples (235 pesticides, various crops, 0.01-0.2 mg/kg) that had been analyzed previously with routine samples over a period of 18 months. At 0.01 mg/kg, the required 95% confidence level (<5% false negatives) was met for 83 compounds. This increased to 185 compounds at the 0.2 mg/kg level. For a number of pesticides, especially at low levels, it had to be concluded that at this stage the method was not fit-for-purpose to reliably demonstrate the absence of pesticides in samples to be analyzed. On the other hand, the fact that the overall detection rate at 0.01 mg/kg was 71% clearly showed that the method does provide added value for the numerous pesticides that are not covered by quantitative methods because the infrequent occurrence does not justify inclusion in such methods. PMID- 22320080 TI - Multiresidue pesticide analysis in ginseng and spinach by nontargeted and targeted screening procedures. AB - Five different mass spectrometers interfaced to GC or LC were evaluated for their application to targeted and nontargeted screening of pesticides in two foods, spinach and ginseng. The five MS systems were capillary GC/MS/MS, GC-high resolution time-of-flight (GC/HR-TOF)-MS, TOF-MS interfaced with a comprehensive multidimensional GC (GCxGC/TOF-MS), an MS/MS ion trap hybrid mass (qTrap) system interfaced with an ultra-performance liquid chromatograph (UPLC-qTrap), and UPLC interfaced to an orbital trap high resolution mass spectrometer (UPLC/Orbitrap HR MS). Each MS system was tested with spinach and ginseng extracts prepared through a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) procedure. Each matrix was fortified at 10 and 50 ng/g for spinach or 25 and 100 ng/g for ginseng with subsets of 486 pesticides, isomers, and metabolites representing most pesticide classes. HR-TOF-MS was effective in a targeted search for characteristic accurate mass ions and identified 97% of 170 pesticides in ginseng at 25 ng/g. A targeted screen of either ginseng or spinach found 94-95% of pesticides fortified for analysis at 10 ng/g with GC/MS/MS or LC/MS/MS using multiple reaction monitoring (MRM) procedures. Orbitrap-MS successfully found 89% of 177 fortified pesticides in spinach at 25 ng/g using a targeted search of accurate mass pseudomolecular ions in the positive electrospray ionization mode. A comprehensive GCxGC/TOF-MS system provided separation and identification of 342 pesticides and metabolites in a single 32 min acquisition with standards. Only 67 or 81% of the pesticides were identified in ginseng and spinach matrixes at 25 ng/g or 10 ng/g, respectively. MS/MS or qTrap-MS operated in the MRM mode produced the lowest false-negative rates, at 10 ng/g. Improvements to instrumentation, methods, and software are needed for efficient use of nontargeted screens in parallel with triple quadrupole MS. PMID- 22320081 TI - Determination of astaxanthin in Haematococcus pluvialis by first-order derivative spectrophotometry. AB - A highly selective, convenient, and precise method, first-order derivative spectrophotometry, was applied for the determination of astaxanthin in Haematococcus pluvialis. Ethyl acetate and ethanol (1:1, v/v) were found to be the best extraction solvent tested due to their high efficiency and low toxicity compared with nine other organic solvents. Astaxanthin coexisting with chlorophyll and beta-carotene was analyzed by first-order derivative spectrophotometry in order to optimize the conditions for the determination of astaxanthin. The results show that when detected at 432 nm, the interfering substances could be eliminated. The dynamic linear range was 2.0-8.0 microg/mL, with a correlation coefficient of 0.9916. The detection threshold was 0.41 microg/mL. The RSD for the determination of astaxanthin was in the range of 0.01 0.06%; the results of recovery test were 98.1-108.0%. The statistical analysis between first-order derivative spectrophotometry and HPLC by T-testing did not exceed their critical values, revealing no significant differences between these two methods. It was proved that first-order derivative spectrophotometry is a rapid and convenient method for the determination of astaxanthin in H. pluvialis that can eliminate the negative effect resulting from the coexistence of astaxanthin with chlorophyll and beta-carotene. PMID- 22320082 TI - Spectrofluorimetric determination of some water-soluble vitamins. AB - Two simple and sensitive spectrofluorimetric methods were developed for determination of three water-soluble vitamins (B1, B2, and B6) in mixtures in the presence of cyanocobalamin. The first one was for thiamine determination, which depends on the oxidation of thiamine HCl to thiochrome by iodine in an alkaline medium. The method was applied accurately to determine thiamine in binary, ternary, and quaternary mixtures with pyridoxine HCl, riboflavin, and cyanocobalamin without interference. In the second method, riboflavin and pyridoxine HCl were determined fluorimetrically in acetate buffer, pH 6. The three water-soluble vitamins (B1, B2, and B6) were determined spectrofluorimetrically in binary, ternary, and quaternary mixtures in the presence of cyanocobalamin. All variables were studied in order to optimize the reaction conditions. Linear relationship was obeyed for all studied vitamins by the proposed methods at their corresponding lambda(exc) or lambda(em). The linear calibration curves were obtained from 10 to 500 ng/mL; the correlation ranged from 0.9991 to 0.9999. The suggested procedures were applied to the analysis of the investigated vitamins in their laboratory-prepared mixtures and pharmaceutical dosage forms from different manufacturers. The RSD range was 0.46 1.02%, which indicates good precision. No interference was observed from common pharmaceutical additives. Good recoveries (97.6 +/- 0.7-101.2 +/- 0.8%) were obtained. Statistical comparison of the results with reported methods shows excellent agreement and indicates no significant difference in accuracy and precision. PMID- 22320083 TI - Differentiation between sulfoaildenafil and its analogs. AB - An analog of aildenafil, which is a potent and highly selective inhibitor of phosphodiesterase 5, was found in a dietary supplement marketed for enhancement of sexual function. The compound was isolated by silica gel column chromatography, and its structure was identified by means of 13C-NMR spectrometry, 1H-NMR spectrometry, high-resolution MS, and X-ray structure determination. The compound was identified to be sulfoaildenafil (other names: thioaildenafil, dimethyl sildenafil thione, and thiomethisosildenafil). Sulfoaildenafil is very similar to the compound thiohomosildenafil. As it is difficult to distinguish between them by LC-photodiode array detector analysis, ultra-performance LC (UPLC)/MS, ion trap LC/MS/MS (LC/IT-MS/MS), and GC/MS were performed. The mass spectra of thiohomosildenafil by UPLC/MS and LC/IT-MS/MS showed mass fragments of m/z 58, 72, and 355, and the mass spectrum by GC/MS showed mass fragments of m/z 56, 72, and 420. Some of these fragments had low intensities, but they were useful for distinguishing between the two compounds. The relationship between aildenafil (other names: dimethylsildenafil and methisosildenafil) and homosildenafil is similar to that between sulfoaildenafil and thiohomosildenafil. Therefore, these compounds were also examined. PMID- 22320084 TI - Quality control of modified xiaoyao san through the determination of 22 active components by ultra-performance liquid chromatography. AB - A simple, sensitive, and reliable ultra-performance liquid chromatography (UPLC) method has been developed for simultaneous determination of 22 major constituents in modified xiaoyao san (MXS), a multiherbal formula. The chromatographic separation was performed on an ACQUITY UPLC BEH C18 column (150 x 2.1 mm, 1.7 microm, particle size), with an aqueous 0.5% acetic acid and acetonitrile mobile phase gradient. The method was validated for linearity (r2 >0.9937), intraday and interday precision (RSD <8.51%), recovery (91.18-107.73%), LOD (0.02-4.17 ng/mL), and LOQ (0.05-12.50 ng/mL). The established method was successfully applied to quantify the 22 marker compounds in MXS, which provided a useful basis of overall evaluation of the quality of MXS. PMID- 22320085 TI - High-performance column liquid chromatographic method for the simultaneous determination of buclizine, tryptophan, pyridoxine, and cyanocobalamin in tablets and oral suspension. AB - An HPLC method was developed and validated for the simultaneous determination of buclizine, tryptophan, pyridoxine, and cyanocobalamin in pharmaceutical formulations. The chromatographic separation was carried out on an RP-C18 column using a mobile phase gradient of methanol, 0.015 M phosphate buffer (pH 3.0), and 0.03 M phosphoric acid at a flow rate of 1.0 mL/min and UV detection at 230, 280, and 360 nm, respectively, for buclizine, tryptophan, pyridoxine, and cyanocobalamin. The method validation yielded good results with respect to linearity (r>0.999), specificity, precision, accuracy, and robustness. The RSD values for intraday and interday precision were below 1.82 and 0.63%, respectively, and recoveries ranged from 98.11 to 101.95%. The method was successfully applied for the QC analysis of buclizine, tryptophan, pyridoxine, and cyanocobalamin in tablets and oral suspension. PMID- 22320086 TI - Stability studies of clonazepam, diazepam, haloperidol, and doxepin with diverse polarities in an acidic environment. AB - Stability of clonazepam, diazepam, haloperidol, and doxepin was determined in acidic solutions. In addition, determination of the kinetic and thermodynamic properties of this stability was carried out. Reaction rate constants (k), half life times (t(0.1) and t(0.5)), and activation energy (Ea) were estimated for the drugs, which differed in polarity expressed with log P values. It was observed that estimated Ea values increased from 42.13 to 125.03 kJ/mol with an increase of lipophilicity (log P) beginning from the most hydrophilic drug (clonazepam, 2.70 log P) to the most lipophilic drug (doxepin, 4.10 log P). All degradation products were studied using an HPLC/electrospray ionization-MS technique in the positive ionization mode. PMID- 22320087 TI - Development and validation of a reversed-phase ultra-performance liquid chromatographic method for assay of lacidipine and related substances. AB - A simple isocratic, RP-ultra-performance LC method was developed and validated for the determination of lacidipine, three process impurities formed during synthesis, and three degradation products present in drug substance and the drug product. An efficient chromatographic separation was achieved on an Acquity BEH C18 column using pH 4.5 ammonium acetate-acetic acid buffer-methanol (70 + 30, v/v) mobile phase. The monitoring wavelength was 240 nm, and the flow rate 0.25 mL/min. Forced degradation studies using acid, alkali, peroxide, water, heat, and light were conducted, and all impurities were separated. The method was validated successfully for specificity, precision, linearity, accuracy, LOD, LOQ, and robustness, according to International Conference on Harmonization guidelines. The linearity of the calibration curve for lacidipine and each impurity was found to be very good (r2 > 0.999). This method is shown to be suitable for analysis of lacidipine to evaluate the quality of drug substance and a drug product. PMID- 22320088 TI - Microsized graphite sensors for potentiometric determination of cyclobenzaprine hydrochloride in pure powder, tablets, and plasma. AB - Two cyclobenzaprine hydrochloride (CZ) microsized graphite selective sensors were investigated with dibutylsebacate as a plasticizer in a polymeric matrix of carboxylated polyvinyl chloride (PVC-COOH) in the case of sensor 1, based on the interaction between the drug and the dissociated COOH groups in the PVC-COOH. Sensor 2 was based on the interaction between the drug and ammonium reineckate, which acted as anionic electroactive material in the presence of polyvinyl chloride matrix. The two sensors were constructed by using 2-hydroxy propyl beta cyclodextrin as an ionophore, which has a significant influence on increasing the membrane sensitivity and selectivity of both sensors. Fast and stable Nernstian responses of 1 x 10(-5) - 1 x 10(-2) and 1 x 10(-4) - 1 x 10(-2) M for the two sensors, respectively, with slopes of 58.6 and 55.5 mV/decade, respectively, over the pH range 2-4 were obtained. The proposed method displayed useful analytical characteristics for determination of CZ in its pure powder form with average recoveries 99.95 +/- 0.23 and 99.61 +/- 0.34% for sensors 1 and 2, respectively, and in plasma with good recoveries. The sensors were also used to determine the intact drug in the presence of its degradate and, thus, could be used as stability-indicating methods. The obtained results by the proposed methods were statistically analyzed and compared with those obtained by the U.S. Pharmacopeia method; no significant difference for either accuracy or precision was observed. Results obtained with the two electrodes revealed their performance characteristics, which were evaluated according to International Union of Pure and Applied Chemistry recommendations. PMID- 22320089 TI - Stability-indicating high-performance column liquid chromatography and high performance thin-layer chromatography methods for the determination of olopatadine hydrochloride in tablet dosage form. AB - This paper describes two simple, specific, accurate, and precise methods for estimation of olopatadine hydrochloride (OLO) in tablet dosage form. The first method is a stability-indicating isocratic RP-HPLC method. The analysis is performed on an RP-18 column using 0.1% orthophosphoric acid (adjusted to pH 4.5 with triethylamine)-acetonitrile (75 + 25, v/v) mobile phase at a flow rate of 1 mL/min. Paracetamol (PAR) was selected as the internal standard. Retention times of OLO and PAR were 11.30 +/- 0.02 and 4.70 +/- 0.03 min, respectively. For the HPTLC method, precoated silica gel 60 F254 aluminum sheets were used as the stationary phase; the mobile phase was methanol-chloroform-ammonia (8 + 2 + 0.1, v/v/v). The detection of the analyte band was carried out at 301 nm, and its Rf value was 0.46 +/- 0.03. The analytical methods were validated according to International Conference on Harmonization guidelines. Linear regression analysis data for the calibration plots showed a good linear relationship between response and concentration in the range of 0.1-1 microg/mL and 0.1-0.9 microg/band for HPLC and HPTLC, respectively. PMID- 22320090 TI - Evaluation of VIDAS Salmonella (SLM) easy Salmonella method for the detection of Salmonella in a variety of foods: collaborative study. AB - The VIDAS Salmonella (SLM) Easy Salmonella method is a specific enzyme-linked fluorescent immunoassay performed in the automated VIDAS instrument. The VIDAS Easy Salmonella method is a simple 2-step enrichment procedure, using pre enrichment followed by selective enrichment in a newly formulated broth, SX2 broth. This new method was compared in a multilaboratory collaborative study to the U.S. Food and Drug Administration's Bacteriological Analytical Manual, Chapter 5 method for five food matrixes (liquid egg, vanilla ice cream, spinach, raw shrimp, and peanut butter) and the U.S. Department of Agriculture's Microbiology Laboratory Guidebook 4.04 method for deli turkey. Each food type was artificially contaminated with Salmonella at three inoculation levels. A total of 15 laboratories representing government, academia, and industry, throughout the United States, participated. In this study, 1583 samples were analyzed, of which 792 were paired replicates and 791 were unpaired replicates. Of the 792 paired replicates, 285 were positive by both the VIDAS and reference methods. Of the 791 unpaired replicates, 341 were positive by the VIDAS method and 325 were positive by the cultural reference method. A Chi-square analysis of each of the six food types was performed at the three inoculation levels tested. For all foods evaluated, the VIDAS Easy SLM method demonstrated results comparable to those of the reference methods for the detection of Salmonella. PMID- 22320091 TI - Reveal E. coli 2.0 method for detection of Escherichia coli O157:H7 in raw beef. AB - Reveal E. coli 2.0 is a new lateral-flow immunodiagnostic test for detection of E. coli O157:H7 and O157:NM in raw beef trim and ground beef. Compared with the original Reveal E. coli O157:H7 assay, the new test utilizes a unique antibody combination resulting in improved test specificity. The device architecture and test procedure have also been modified, and a single enrichment protocol was developed which allows the test to be performed at any point during an enrichment period of 12 to 20 h. Results of inclusivity and exclusivity testing showed that the test is specific for E. coli serotypes O157:H7 and O157:NM, with the exception of two strains of O157:H38 and one strain of O157:H43 which produced positive reactions. In internal and independent laboratory trials comparing the Reveal 2.0 method to the U.S. Department of Agriculture-Food Safety and Inspection Service reference culture procedure for detection of E. coli O157:H7 in 65 and 375 g raw beef trim and ground beef samples, there were no statistically significant differences in method performance with the exception of a single internal trial with 375 g ground beef samples in which the Reveal method produced significantly more positive results. There were no unconfirmed positive results by the Reveal assay, for specificity of 100%. Results of ruggedness testing showed that the Reveal test produces accurate results even with substantial deviation in sample volume or device incubation time or temperature. However, addition of the promoter reagent to the test sample prior to introducing the test device is essential to proper test performance. PMID- 22320092 TI - BIOTECON diagnostics foodproof E. coli O157 detection kit, 5' nuclease for E. coli O157 in combination with foodproof ShortPrep II Kit. AB - The method describes the detection of Escherichia coli O157 in food. The method is based on real-time PCR using hydrolysis probes (5' Nuclease). This advanced PCR method was designed to reduce the time necessary to achieve results from PCR reactions and enable the user to monitor the amplification of the PCR product simultaneously in real time. After DNA isolation using the BIOTECON foodproof ShortPrep II Kit designed for the rapid preparation of E. coli O157 DNA for direct use in PCR, the real-time detection of E. coli O157 DNA is carried out using the foodproof E. coli O157 Detection Kit. The kit provides primers and hydrolysis probes for sequence-specific detection, convenient premixed reagents, and controls for reliable interpretation of results. For repeatability studies three different foods (egg salad, large bockwurst/frankfurter, and apple juice) were analyzed, chosen from the 15 food groups recommended by the AOAC Research Institute for E. coli O157 detection. From each food, 20 samples were inoculated with a low level (1-10 CFU/25 g) and 20 samples with a high level (10-50 CFU/25 g) ofE. coli O157. Additionally, five nonspiked samples were prepared from each food. Depending on the matrix, the food samples were examined with the test kits and compared with the cultural methods according to the U.S. Food and Drug Administration Bacteriological Analytical Manual or the U.S. Department of Agriculture/Food Safety and Inspection Service Microbiology Laboratory Guidebook. PMID- 22320093 TI - LC/MS method using cloud point extraction for the determination of permitted and illegal food colors in liquid, semiliquid, and solid food matrixes: single laboratory validation. AB - A cloud point extraction method is reported using LC/MS for the determination of regulated water-soluble food colors (Allura Red, Sunset Yellow, erythrosine, and tartrazine) and banned fat-soluble synthetic azo dyes (Sudan I, II, III, and IV; Red B; 7B; Black B; Red G; Metanil Yellow; and Rhodamine B). The extraction of all 14 colors was carried out with cloud point extraction using the nonionic surfactant Triton X 114. Optimized conditions for cloud point extraction were 3% Triton X 114 (w/v), 0.1 M ammonium acetate, and heating at 50 degrees C for 30 min. This approach proved effective in giving quantitative recoveries from a diverse range of food matrixes, and optimized LC gave baseline chromatographic separation for all colors including Sudan IV and Red B. Single-laboratory validation was performed with spiking into liquid matrixes (wine and homemade wine), semiliquid matrixes (sauce and homemade paprika paste), and solid matrixes (spice and homemade chili powder) using the respective blank matrixes for matrix matched calibration. The LOQ values for water-soluble colors were in the range of 15-150 mg/kg, and for the fat-soluble colors, 0.1-1.5 mg/kg. The mean recovery values were in the range of 69.6-116.0% (except Allura Red and Sunset Yellow in wine, for which recoveries were lower). The mean RSDs for colors were in the range of 4.0-14.8%. A small survey was conducted of samples of confectionery products, dried fruits, wines, bitter sodas, juices, sauces, pastes, and spices, which demonstrated the applicability of the method to a diverse selection of real food samples. Allura Red was detected in strawberry jelly and Sunset Yellow in artificial saffron. PMID- 22320094 TI - Sensitive detection of soy (Glycine max) by real-time polymerase chain reaction targeting the mitochondrial atpA gene. AB - Detection of trace amounts of allergens is essential for correct labeling of food products by the food industry. PCR-based detection methods currently used for this purpose are targeting sequences of DNA present in the cell nucleus. In addition to nuclear DNA, a substantial amount of mitochondrial DNA (mtDNA) copies are present in the cytoplasm of eukaryotic cells. The nuclear DNA usually consists of a set of DNA molecules present in two copies per cell, whereas mitochondrial DNA is present in a few hundred copies per cell. Thus, an increase in sensitivity can be expected when mtDNA is used as the target. In this study, we present a reporter probe-based real-time PCR method amplifying the mitochondrial gene of the alpha chain of adenosine triphosphate synthetase from soy. Increase in sensitivity was examined by determining the minimal amount of soy DNA detectable by mtDNA and nuclear DNA (nDNA) amplification. Additionally, the LOD of soy in a food matrix was determined for mtDNA amplification and compared to the LOD determined by nDNA amplification. As food matrix, a model spice spiked with soy flour was used. Sensitivity of PCR-based soy detection can be increased by using mtDNA as the target. PMID- 22320095 TI - A simple method for simultaneous determination of basic dyes encountered in food preparations by reversed-phase HPLC. AB - The present method utilizes a simple pretreatment step, cleanup on polyamide SPE cartridges, and HPLC resolution on reversed-phase C18 for the detection of the three basic nonpermitted dyes encountered in food matrixes. Polyamide cartridges were chosen because both acidic and basic dyes can be cleaned up due to their amphoteric nature. Analysis was performed on a reversed-phase C18 micro-Bondapak column using the isocratic mixture of acetonitrile-sodium acetate with a flow rate of 1.5 mL/min and a programmable lambda(max) specific visible detection to monitor colors, achieving higher sensitivity and expanded scope to test multicolor blends. All the colors showed linearity with the regression coefficient, from 0.9983 to 0.9995. The LOD and LOQ ranged between 0.107 and 0.754 mg/L and 0.371 and 2.27 mg/L or mg/kg, respectively. The intraday and interday precision gave good RSDs, and percentage recoveries in different food matrixes ranged from 75 to 96.5%. The study demonstrates that the use of a combination of a simple SPE cleanup and HPLC resolution with UV-Vis end point detection was successful in screening the presence of these three basic nonpermitted dyes individually or in blend, in a variety of food matrixes. PMID- 22320096 TI - Determination of some organophosphorus and azole group pesticides in water samples by dispersive liquid-liquid microextraction coupled with GC/MS. AB - A dispersive liquid-liquid microextraction (DLLME) procedure coupled with GC/MS detection is described for preconcentration and determination of some organophosphorus and azole group pesticides from water samples. Experimental conditions affecting the DLLME procedure were optimized by means of an experimental design. A mixture of 60 microL chlorobenzene (extraction solvent) and 750 microL acetonitrile (disperser solvent), 3.5 min extraction time, and 7.5 mL aqueous sample volume were chosen for the best recovery by DLLME. The linear range was 1.6-32 microg/L. The LOD ranged from 48.8 to 68.7 ng/L. The RSD values for organophosphorus and azole group pesticides at spiking levels of 3, 6, and 9 microg/L in water samples were in the range of 1.1-12.8%. The applicability and accuracy of the developed method were determined by analysis of spiked water samples, and the recoveries of the analyzed pesticides from artesian, stream, and tap waters at spiking levels of 3, 6, and 9 microg/L were 89.3-105.6, 89.5-103.0, and 92.0-111.3%, respectively. PMID- 22320097 TI - Simple analysis of naphthalene, fluorene, and anthracene in whole blood by gas chromatography/mass spectrometry after headspace-solid phase microextraction. AB - A simple and sensitive method for the simultaneous analysis of naphthalene, fluorene, and anthracene in whole blood was developed using headspace-solid-phase microextraction (SPME) and GC/MS. A 0.5 g whole blood sample, 5 microL naphthalene, fluorene, and anthracene (50 microg/mL) as spiked standards, and 0.5 mL sodium hydroxide were placed into a 12 mL vial and sealed rapidly. The vial was immediately heated to 70 degrees C in an aluminium block heater, the needle of the SPME device was inserted through the septum of the vial, and the extraction fiber was exposed to the headspace for 15 min. Afterwards, the compounds extracted by the fiber were desorbed simultaneously by exposing the fiber in the gas chromatograph injection port. No interferences were found, and the time for analysis was about 30 min for one sample. This method was applied to a suicide case in which the victim ingested naphthalene, fluorene, and anthracene. PMID- 22320098 TI - A new cadmium reduction device for the microplate determination of nitrate in water, soil, plant tissue, and physiological fluids. AB - A reusable catalytic reductor consisting of 96 copperized-cadmium pins attached to a microplate lid was developed to simultaneously reduce nitrate (NO3-) to nitrite (NO2-) in all wells of a standard microplate. The resulting NO2- is analyzed colorimetrically by the Griess reaction using a microplate reader. Nitrate data from groundwater samples analyzed using the new device correlated well with data obtained by ion chromatography (r2 = 0.9959). Soil and plant tissue samples previously analyzed for NO3- in an interlaboratory validation study sponsored by the Soil Science Society of America were also analyzed using the new technique. For the soil sample set, the data are shown to correlate well with the other methods used (r2 = 0.9976). Plant data correlated less well, especially for samples containing low concentrations of NO3-. Reasons for these discrepancies are discussed, and new techniques to increase the accuracy of the analysis are explored. In addition, a method is presented for analyzing NO3- in physiological fluids (blood serum and urine) after matrix modification with Somogyi's reagent. A protocol for statistical validation of data when analyzing samples with complex matrixes is also established. The simplicity, adaptability, and low cost of the device indicate its potential for widespread application. PMID- 22320099 TI - Homogeneity and stability studies during the preparation of a laboratory reference material of soy leaves for the determination of metals. AB - The homogeneity and stability of metals were tested in a candidate laboratory reference material of soy leaves. Inductively coupled plasma-optical emission spectrometry was used to quantify calcium, magnesium, manganese, iron, zinc, copper, and vanadium. A 6 kg amount of the material, which was dried, ground, and classified as mesh 60, was distributed among 100 bottles. The between-bottle homogeneity test was established by analyzing two subsamples from nine bottles. For the within-bottle test, five determinations of each element of a single bottle were performed. The stability test was performed at temperatures of -10, +27, and +40 degrees C, and after storage times of 4, 12, 24, and 52 weeks. The obtained results indicated that the material was homogeneous and stable under the conditions studied. PMID- 22320100 TI - Preparation and identification of generic antigens and broad-spectrum monoclonal antibodies for detection of organophosphorus pesticides. AB - A simple, rapid, and high-sensitivity assay was developed to detect the multiresidue of organophosphorus pesticides (OPs) in the environment and food. Two separate generic haptens (Hapten A and B) with same O,O-dimethyl phosphorothioate group and aromatic ring and different spacer arms were synthesized and conjugated to bovine serum albumin (BSA) for immunogens and to ovalbumin (OVA) for coating antigens to study the effect of hapten and coating antigen heterology on immunoassay sensitivity. A broad-spectrum monoclonal antibody (MAb) was produced and a competitive ELISA developed using Hapten B-BSA as the immunogen and Hapten A-OVA as the coating antigen for the multiresidue determination of OPs, including parathionmethyl, fenitrothion, fenthion, chlorthion, and fenchlorphos. Several assay conditions, including organic solvent, pH, ionic strength, and incubation time, were studied sequentially to optimize the immunoassay. Using the optimal assay, 50% inhibition concentration values were estimated to be 34.5, 47.5, 79.8, 125.2, and 373.1 ng/mL for parathionmethyl, fenitrothion, fenthion, chlorthion, and fenchlorphos, respectively. The results indicated that the MAb showed specificity to all the above five OPs, and the assay could be developed for multiresidue determinations. PMID- 22320101 TI - Polyacrylic acid-modified alumina for solid-phase extraction and preconcentration of trace iron and chromium from plant samples. AB - A new method is presented for simultaneous preconcentration of trace Fe(III) and Cr(III) by using polyacrylic acid-alumina as a sorbent. The separation/preconcentration conditions of analytes were investigated, including effect of pH, flow rate, elution conditions, sample volume, and interfering ions. At pH 4, the maximum sorption capacities of Fe3+ and Cr3+ were 8.0 and 13.0 mg/g, respectively, by the column method. The linearity was maintained in the concentration range of 0.175-6.0 x 10(3) ng/mL for iron and 0.175-8.0 x 10(3) ng/mL for chromium in the original solution. The RSD values under optimum conditions were +/- 1.73 and +/- 1.28% for 2.0 microg/mL Fe and Cr, respectively. The preconcentration factor was 400 for both of the elements, and detection limits were 0.025 and 0.023 ng/mL for Fe and Cr in the original solutions. The proposed method was successfully applied to the determination of trace amounts of Fe and Cr in plant samples. PMID- 22320102 TI - Preparation and characterization of porous calcium titanate-based coated glass fiber filter material and its application in determination of lead and cadmium ion concentrations in water. AB - Glass fiber filter coated with a porous block adsorption agent of calcium titanate (GPCTO) was prepared by the citric acid sol-gel method, and characterized by X-ray diffraction, scanning electron microscopy, and FTIR spectrophotometry. Its Pb2+ and Cd2+ adsorption properties from water were studied. Adsorption and elution were investigated under different conditions, as were the thermodynamics and kinetics of adsorption, using Cd ion as representative. Calcium titanate may react with glass fiber, forming Si-O-Ti and B-O-Ti bonds and becoming a composite adsorbent. The Pb and Cd ions were quantitatively retained at pH 4-9; their adsorption capacities by the GPCTO were 199.72 and 19.68 mg/g, respectively. The isothermal data were described by the Langmuir equation. The dynamic data followed the pseudo-second-order kinetic model well. The enthalpy change (AH) of the adsorption process was 37.160 kJ/mol. At various temperatures, Gibbs free energy changes (delta G) were negative, and entropy changes (delta S) were positive. The activation energy (Ea) was 38.127 kJ/mol for the adsorption. Cd ion adsorption by the GPCTO was endothermic and spontaneous. The adsorbed Pb and Cd ions were completely recovered by elution with 2 M HNO3. The Pb+ and Cd2+ concentration factors were up to 200. The method has been applied to the preconcentration for flame atomic absorption spectrometric determinations of trace Pb and Cd ions in water samples. The recoveries were 95.2 to 102.4% for Pb and 92.2 to 98.0% for Cd. PMID- 22320103 TI - [Genome, environment and plasticity of the brain underlying individual adaptation]. AB - Epigenetic mechanisms mediate the interaction between environment and genome. On molecular level, these mechanisms are active in plastic processes of the brain and influence brain function and the person's ability to adapt to the environment. Genomic variations provide individual options for this adaptation, and a spectrum of behavioral patterns necessary for species preservation. Adaptation processes may also be harmful in respect of individual health, leading even to psychiatric illnesses, but are still meaningful as seen through the person's inner experience, genome or environment. PMID- 22320104 TI - [Brain imaging of patients with memory disorders]. AB - Indications for brain imaging include potentially treatable intracranial causes (e.g. normal-pressure hydrocephalus, tumors, subdural hematoma) and especially characteristic features of memory disorders and differential diagnostics of such conditions. Since the primary structural changes in the most common progressive memory disorder, Alzheimer's disease, are seen in the inner temporal lobe, appropriate imaging of these structures is essential in early diagnosis. PMID- 22320105 TI - [Faecal calprotectin in inflammatory bowel disease]. AB - Calprotectin is a protein released especially from neutrophilic leukocytes and secreted into the intestine during inflammation of the intestinal mucosa. It can be assayed from the feces. Faecal calprotectin has proven to be a useful marker in the diagnostics and monitoring of inflammatory bowel diseases, and application of the assay has been extended from pediatric patients also to adults. Faecal calprotectin is highly elevated in active inflammatory bowel disease, and elevated values in symptomless patients seem to be predictive of exacerbation especially in ulcerative colitis and in Crohn's disease colitis. PMID- 22320106 TI - [Idiopathic pulmonary fibrosis -- progress in sight]. AB - The review presents the main aspects of a new international statement on idiopathic pulmonary fibrosis (IPF), therapeutic trials with a new drug, pirfenidone, and a new Finnish IPF register. It is desirable to have patients reported to the register with the best possible coverage in order to obtain a view about the prevalence of the disease in Finland. In the future, the register can be utilized to standardize the diagnostics and treatment of IPF, and to rapidly launch therapeutic trials and investigations with new drugs. PMID- 22320107 TI - [Fibrin glue in gastrointestinal fistulas]. AB - Gastrointestinal fistulas are relatively uncommon, and therefore difficult to diagnose. They occur after surgical procedures and result from various diseases or injuries. The diagnosis is usually based on contrast-enhanced computed tomography. When occurring, these fistulas are associated with considerable morbidity and even mortality. One third of the fistulas heal spontaneously, while the rest have usually been operated with varying success. During the last years, gastrointestinal fistulas have been successfully treated endoscopically with fibrin glue. PMID- 22320108 TI - [Inhalation of hypertonic saline: a promising therapy in bronchiectasis]. AB - BACKGROUND: Accumulation of mucus into the lungs in bronchiectasis lowers the patients' quality of life. Hypertonic aerosols stimulate the removal of mucus. MATERIAL AND METHODS: 37 bronchiectasis patients without cystic fibrosis inhaled 4 ml of a 6 per cent saline solution twice a day for three months. Amount of coughs, PEF values and oxygen saturation associated with the first inhalation were measured. Quality of life was assessed by the SGRQ (St George's Respiratory Questionnaire). RESULTS: Inhalation did not decrease oxygen saturation but did lower slightly the PEF value. SGRQ score decreased by 9.2 points on the average (p = 0.002) indicating clinically significant improvement in quality of life. CONCLUSIONS: Hypertonic saline inhalations in patients with brochiectasis are safe and may also improve quality of life. PMID- 22320110 TI - [Surgeons in the Czech Republic]. PMID- 22320109 TI - [Mycoplasma hominis may cause soft tissue infections]. AB - Mycoplasmas belong to the smallest micro-organisms that are independent of animal or plant cells. They are classified as bacteria, since their cultivation does not require any cells. Mycoplasma hominis is a commensal of the human urogenital region, but may sometimes cause even life-threatening, slow-healing soft tissue infections. Ureaplasma urealyticum may cause similar infections. It is important both for clinicians and the laboratory to suspect mycoplasma, when clinical picture indicates infection and the infectious agent cannot be shown by ordinary culturing methods. PMID- 22320111 TI - [High chronic ileus and subrenal aortic aneurysm -- an interesting case review]. AB - Ileus caused by small intestinal obturation due to an enterolith, as a complication of jejunal diverticulosis, is rare, however, a number of case reviews describing the conditions can be found in literature. The presented case review documents difficulties with entherolith ileus diagnostics and its management together with a growing abdominal aneurysm, as a single step procedure. PMID- 22320112 TI - [Pancreatic trauma]. AB - Injuries to the pancreas are relatively rare, occurring in around 10% of case involving serious trauma to the abdominal cavity, with 65% of such injuries resulting trauma occurs only exceptionally, involving only 5% of all injuries. The mortality of this entity is influenced by many factors, especially the age of the injured person, the seriousness of the injury, the duration of the shock, the potentially associated trauma, early diagnosis and correct selection of suitable treatment. The authors present here 4 case reports describing injuries to the pancreas and documenting the diagnostic and therapeutic approaches in cases of this very serious trauma. PMID- 22320113 TI - [Heterotopic pancreas in the stomach wall -- a rare histological diagnosis of submucous lesson -- casuistic report]. AB - Heterotopic pancreas (HP) is defraed as abnormally localized pancreatic tissue without any anatomical and vascular connection with pancreas. Incidence of HP is 0.2-0.5% of patients underwent upper medial laparotomy. The most common symptoms of HP are abdominal discomfort and pain, upper gastrointestinal bleeding and intermittent bowel obstruction. Gastroscopy is the most commonly used first diagnostic procedure. Ultrasound evaluation, computer tomography and namely endoscopic ultrasound evaluation are useful imaging procedures of HP. Casuistic report of patient with upper gastrointestinal bleeding is presented. Imaging procedures have recorded stomach tumor 3cm in diameter in back wall of stomach. Billroth II resection of stomach was performed. Histological evaluation of removed part of stomach recorded heterotopic pancreas type 1 of Heinrich classification. HP diagnosis before surgery is difficult because of submucous localization of lesion. Fine needle biopsy during gastroscopy is one of diagnostic possibilities without surgery. Endoscopic excision of lesion is possible if histological evaluation by fine needle biopsy is successful and anatomical localization is appropriate. The most of patients need surgical excision of HP. Peroperative histological evaluation allows a minimalization of excision area. Opinions of asymptomatic HP treatment are ambiguous. The most of published papers recommend excision of asymptomatic HP also, because of risk of next complications. PMID- 22320114 TI - [Percutaneous treatment of symptomatic massive bile ducts stones after previous surgery with biliodigestive anastomosis -- report of three cases]. AB - PURPOSE: Presentation of our own experience with percutaneous treatment of symptomatic bile-duct stones like late complication in patients with biliodigestive anastomosis. METHOD: Three symptomatic female patients with biliodigestive anastomosis and acutely symptomatic with proven bile-duct stones above anastomosis were treated with initial percutaneous transhepatic drainage and later via percutaneous route using of endoscopic lithotryptor with special technique. RESULTS: All procedures were successful without complication, the patients are free of biliary symptoms in the long term. CONCLUSION: Percutaneous removal of bile-duct stones in patients with biliodigestive anastomosis is safe and effective method which can be used as an alternative to surgery. PMID- 22320115 TI - [Thrombolytic therapy of acute peripheral arterial occlusions of limb arteries]. AB - INTRODUCTION: Thrombolytic therapy is a method of solution of thrombotic arterial occlusions of limbs using the physiological process of fibrinolysis. The severity of limb ischemia is the crucial for therapy. If immediate recanalization of arterial system is necessary than primarily surgical teratment is chosen. THE METHOD: The arterial closures in infrainguinal localization are indicated for thrombolysis. Especially occlusions of crural vessels and the closures of previous vascular reconstruction (bypass) are indicated. The methods of local intra-arterial thrombolysis with application of recombinant tissue plasminogen activator, (rt-PA Actilyse) through catheter introduced into the level of thrombotic occlusion by Seldinger's Metod are used in our department. RESULTS: The authors present retrospectively analyzed set of 51 patients (12 women and 39 men aged 33 to 85 years) with acute arterial occlusion solved with thrombolytic therapy in the period 02/2007 - 03/2010. Complete recanalization was achieved in 43 cases (patients) (84%), high amputation of limbs was performed in 3 cases (5.9%). PMID- 22320116 TI - [Legal requirements concerning textile medical products]. AB - Presently, more and more often the medical public is concerned with questions regarding use of textile products intended for multiple application at operating theatres. Such questions have been evoked especially by spreading information on restrictions regarding purchase and us of health care products or medical means made from cotton of intended for multiple application. Based on this information preference is given to significantly more expensive products intended for single use only. This decision is being reasoned by conditions given by European standard EN 13795 reportedly prohibiting the application of cotton within health care. Since this piece of information is not precise, we would like to sum-up legislative situation within this area. PMID- 22320117 TI - [Incisional hernia following laparoscopy, complicated by perforated gangrenic appendicitis -- a case review]. AB - Acute appendicitis is the commonest cause of acute abdomen. Early indication for surgery -- appendectomy, plays the key role in its therapy. The rate of incisional hernias (of all operated hernias) is high and they are, to a certain extent, caused by technical, mechanical factors and the patient himself. The authors present a case review of a female patient, presenting with atypical urgent abdomen, who was hospitalized with a diagnosis of advanced absces of the abdominal wall, resp. strangulated incisional hernia. Surgical revision confirmed that the condition was caused by perforated gangrenous appendicitis incisional hernia following laparoscopy. Acute appendicits is a very rare complication of the incisional hernia, and it is practically impossible to make its diagnosis based on clinical examination. Its diagnosis may be facilitated using visualization examination methods, however, its final diagnosis can only be made during surgical revision indicated for progressing acute abdomen. PMID- 22320118 TI - [Amyand's hernia -- a rare cause of acute abdomen]. AB - BACKGROUND: Amyand's hernia is a rare condition in which the appendix is positioned in the inguinal hernia sac. Acute appendicitis in this situation is a extremely rare and only a few reports are found in the literature. METHODS: Case report RESULTS AND CONCLUSION: We report a case of acute gangrenous appendicitis with the perforation at the tip of the appendix, which was incarcerated in the right groin. We conduct a review of the literature, emphasizing possible causes and suggesting a predisposing factor for the condition. PMID- 22320119 TI - Possible impact of hemodynamic factors on the development of recurrent reflux in primary varicose veins. AB - Definition of reflux as a centrifugal flow within an incompetent vein connecting both poles of the ambulatory pressure gradient and causing ambulatory venous hypertension is presented. Recurrent reflux occurs also after correctly performed crossectomy and stripping. Growth of new vessels (neo-angiogenesis) or dilatation of pre-existing venous channels (vascular remodelling) has been claimed to be the main cause of recurrences in these instances. Attempts to blockade the development of recurrent reflux in the groin by inserting mechanical barriers over the ligated saphenofemoral junction failed to prevent recurrences. The synergistic effect of two hemodynamic factors - pressure difference between the femoral vein and the saphenous remnant in the thigh on one side, and the propensity to restore centrifugal flow on the other side - may play a crucial role in the development of recurrent reflux. Pressure gradient apparently triggers the event. Restoration of centrifugal flow might be the pre-programmed phenomenon that improves compromised blood supply in arterial occlusions, but evokes recurrent reflux in incompetent superficial veins. In this way, it can be explained why recurrent reflux can occur after any therapeutic procedure. PMID- 22320120 TI - [Giant peritoneal loose bodies]. AB - Presentation of a very unusual case report "big bang" theory and references. PMID- 22320121 TI - Incorporation of heterocycles into the backbone of peptoids to generate diverse peptoid-inspired one bead one compound libraries. AB - Combinatorial libraries of peptoids (oligo-N-substituted glycines) have proven to be useful sources of protein ligands. Each unit of the peptoid oligomer is derived from 2-haloacetic acid and a primary amine. To increase the chemical diversity available in peptoid libraries, we demonstrate here that heterocyclic halomethyl carboxylic acids can be employed as backbone building blocks in the synthesis of peptoid-based oligomers. Optimized conditions are reported that allow the creation of large, high quality combinatorial libraries containing these units. PMID- 22320123 TI - Sulphur tales: a tribute on the occasion of the 90th birthday of Heimo Nielsen. PMID- 22320122 TI - Mycobacterium tuberculosis: success through dormancy. AB - Tuberculosis (TB) remains a major health threat, killing nearly 2 million individuals around this globe, annually. The only vaccine, developed almost a century ago, provides limited protection only during childhood. After decades without the introduction of new antibiotics, several candidates are currently undergoing clinical investigation. Curing TB requires prolonged combination of chemotherapy with several drugs. Moreover, monitoring the success of therapy is questionable owing to the lack of reliable biomarkers. To substantially improve the situation, a detailed understanding of the cross-talk between human host and the pathogen Mycobacterium tuberculosis (Mtb) is vital. Principally, the enormous success of Mtb is based on three capacities: first, reprogramming of macrophages after primary infection/phagocytosis to prevent its own destruction; second, initiating the formation of well-organized granulomas, comprising different immune cells to create a confined environment for the host-pathogen standoff; third, the capability to shut down its own central metabolism, terminate replication, and thereby transit into a stage of dormancy rendering itself extremely resistant to host defense and drug treatment. Here, we review the molecular mechanisms underlying these processes, draw conclusions in a working model of mycobacterial dormancy, and highlight gaps in our understanding to be addressed in future research. PMID- 22320125 TI - Quantum plasmonics: nonlinear effects in the field enhancement of a plasmonic nanoparticle dimer. AB - A fully quantum mechanical investigation using time-dependent density functional theory reveals that the field enhancement in a coupled nanoparticle dimer can be strongly affected by nonlinear effects. We show that both classical as well as linear quantum mechanical descriptions of the system fail even for moderate incident light intensities. An interparticle current resulting from the strong field photoemission tends to neutralize the plasmon-induced surface charge densities on the opposite sides of the nanoparticle junction. Thus, the coupling between the two nanoparticles and the field enhancement is reduced as compared to linear theory. A substantial nonlinear effect is revealed already at incident powers of 10(9) W/cm(2) for interparticle separation distances as large as 1 nm and down to the touching limit. PMID- 22320124 TI - Efficacy of three drugs for protecting against gentamicin-induced hair cell and hearing losses. AB - BACKGROUND AND PURPOSE Exposure to an ototoxic level of an aminoglycoside can result in hearing loss. In this we study investigated the otoprotective efficacy of dexamethasone (DXM), melatonin (MLT) and tacrolimus (TCR) in gentamicin (GM) treated animals and cultures. EXPERIMENTAL APPROACH Wistar rats were divided into controls (treated with saline); exposed to GM only (GM); and three GM-exposed groups treated with either DXM, MLT or TCR. Auditory function and cochlear surface preparations were studied. In vitro studies of oxidative stress, pro inflammatory cytokine mRNA levels, the MAPK pathway and caspase-3 activation were performed in organ of Corti explants from 3-day-old rats. KEY RESULTS DXM, MLT and TCR decreased levels of reactive oxygen species in GM-exposed explants. The mRNA levels of TNF-alpha, IL-1beta and TNF-receptor type 1 were significantly reduced in GM + DXM and GM + MLT groups. Phospho-p38 MAPK levels decreased in GM + MLT and GM + TCR groups, while JNK phosphorylation was reduced in GM + DXM and GM + MLT groups. Caspase-3 activation decreased in GM + DXM, GM + MLT and GM + TCR groups. These results were consistent with in vivo results. Local treatment of GM-exposed rat cochleae with either DXM, MLT or TCR preserved auditory function and prevented auditory hair cell loss. CONCLUSIONS AND IMPLICATIONS In organ of Corti explants, GM increased oxidative stress and initiated an inflammatory response that led to the activation of MAPKs and apoptosis of hair cells. The three compounds tested demonstrated otoprotective properties that could be beneficial in the treatment of ototoxicity-induced hearing loss. PMID- 22320126 TI - Pathogen reduction treatment of buffy coat platelet concentrates in additive solution induces proapoptotic signaling. AB - BACKGROUND: Pathogen reduction technology (PRT) can potentially reduce the risk of transfusion-transmitted infections. However, PRT treatment of platelet (PLT) concentrates also results in reduced PLT quality and increased markers of apoptosis during storage. The aim of this study was to investigate changes to the expression and activation of proteins involved in apoptosis signaling. STUDY DESIGN AND METHODS: Samples from riboflavin and ultraviolet light PRT-treated and untreated (control) buffy coat-derived PCs in 70% SSP+ and 30% plasma were taken on Days 1, 5, and 7 of storage. Phosphatidylserine (PS) exposure, expression of Bcl-2 family proteins, cytochrome c release, and cleavage of caspase-3 and caspase-3 substrates were analyzed using flow cytometry and Western blotting. RESULTS: Compared to untreated controls, markers of apoptosis signaling were increased after PRT and subsequent storage. PS exposure on the PLT outer membrane was significantly higher after PRT on Days 5 and 7 of storage (p < 0.05). Expression of proapoptotic Bak and Bax was higher after PRT and subsequent storage. Cytochrome c release and caspase-3 cleavage were also greater and occurred earlier in the PRT-treated PLTs. The cleavage of caspase-3 substrates gelsolin and ROCK I were also increased after PRT, compared to untreated controls. CONCLUSIONS: This study demonstrated an increase in proapoptotic signaling during PLT storage, which was exacerbated by PRT. Many of these differences emerged outside the current 5-day storage period. These changes may not currently influence PLT transfusion quality, but will need to be carefully evaluated when considering extending PLT storage beyond 5 days. PMID- 22320127 TI - Maximum principal strain correlates with spinal cord tissue damage in contusion and dislocation injuries in the rat cervical spine. AB - The heterogeneity of the primary mechanical mechanism of spinal cord injury (SCI) is not currently used to tailor treatment strategies because the effects of these distinct patterns of acute mechanical damage on long-term neuropathology have not been fully investigated. A computational model of SCI enables the dynamic analysis of mechanical forces and deformations within the spinal cord tissue that would otherwise not be visible from histological tissue sections. We created a dynamic, three-dimensional finite element (FE) model of the rat cervical spine and simulated contusion and dislocation SCI mechanisms. We investigated the relationship between maximum principal strain and tissue damage, and compared primary injury patterns between mechanisms. The model incorporated the spinal cord white and gray matter, the dura mater, cerebrospinal fluid, spinal ligaments, intervertebral discs, a rigid indenter and vertebrae, and failure criteria for ligaments and vertebral endplates. High-speed (~ 1 m/sec) contusion and dislocation injuries were simulated between vertebral levels C3 and C6 to match previous animal experiments, and average peak maximum principal strains were calculated for several regions at the injury epicenter and at 1-mm intervals from +5 mm rostral to -5 mm caudal to the lesion. Average peak principal strains were compared to tissue damage measured previously in the same regions via axonal permeability to 10-kD fluorescein-dextran. Linear regression of tissue damage against peak maximum principal strain for pooled data within all white matter regions yielded similar and significant (p<0.0001) correlations for both contusion (R(2)=0.86) and dislocation (R(2)=0.52). The model enhances our understanding of the differences in injury patterns between SCI mechanisms, and provides further evidence for the link between principal strain and tissue damage. PMID- 22320128 TI - Solar cell sensitizer models [Ru(bpy-R)2(NCS)2] probed by spectroelectrochemistry. AB - Complexes [Ru(bpy-R)(2)(NCS)(2)], where R = H (1), 4,4'-(CO(2)Et)(2) (2), 4,4' (OMe)(2) (3), and 4,4'-Me(2) (4), were studied by spectroelectrochemistry in the UV-vis and IR regions and by in situ electron paramagnetic resonance (EPR). The experimental information obtained for the frontier orbitals as supported and ascertained by density functional theory (DFT) calculations for 1 is relevant for the productive excited state. In addition to the parent 1, the ester complex 2 was chosen for its relationship to the carboxylate species involved for binding to TiO(2) in solar cells; the donor-substituted 3 and 4 allowed for better access to oxidized forms. Reflecting the metal-to-ligand (Ru -> bpy) charge-transfer characteristics of the compounds, the electrochemical and EPR results for compounds 1-4 agree with previous notions of one metal-centered oxidation and several (bpy-R) ligand-centered reductions. The first one-electron reduction produces extensive IR absorption, including intraligand transitions and broad ligand-to-ligand intervalence charge-transfer transitions between the one electron-reduced and unreduced bpy-R ligands. The electron addition to one remote bpy-R ligand does not significantly affect the N-C stretching frequency of the Ru(II)NCS unit. Upon oxidation of Ru(II) to Ru(III), however, the single N-C stretching band exhibits a splitting and a shift to lower energies. The DFT calculations serve to reproduce and understand these effects; they also suggest significant spin density on S for the oxidized form. PMID- 22320129 TI - Characterization of the conformational equilibrium between the two major substates of RNase A using NMR chemical shifts. AB - Following the recognition that NMR chemical shifts can be used for protein structure determination, rapid advances have recently been made in methods for extending this strategy for proteins and protein complexes of increasing size and complexity. A remaining major challenge is to develop approaches to exploit the information contained in the chemical shifts about conformational fluctuations in native states of proteins. In this work we show that it is possible to determine an ensemble of conformations representing the free energy surface of RNase A using chemical shifts as replica-averaged restraints in molecular dynamics simulations. Analysis of this surface indicates that chemical shifts can be used to characterize the conformational equilibrium between the two major substates of this protein. PMID- 22320130 TI - Management of 'double teeth' in children and adolescents. AB - BACKGROUND: Abnormally, large teeth are often referred to as 'double teeth'. These can pose numerous challenges for the clinician. There is no published protocol on the management of double teeth. AIM: To review the published literature and also patients managed at the Eastman Dental Hospital (EDH) and to develop a clinical protocol for the management of double teeth in children and adolescents. DESIGN: Literature was searched (Medline and Embase) and data collated. Patient notes of cases managed at the EDH were reviewed. RESULTS: Eighty-one teeth from 53 papers and 22 patients were included in the review. Success criteria were only reported in 32 papers and were variable. Twenty-three papers had no follow-up period. The main factor in determining the management of a double tooth was root and root canal system morphology. The treatment of choice in teeth with separate roots was hemisection and in those with a single root was crown modification or extraction. CONCLUSION: It was not possible to determine the best management strategies because of the variable reporting in the literature. The authors have proposed a protocol for management and a data collection sheet for essential information needed when reporting on double teeth cases. PMID- 22320133 TI - Tattoo and taboo: on the meaning of tattoos in the analytic process. AB - Tattooing projects a visual image in transference to form a backdrop for the most salient unconscious inner conflicts arising during an ongoing analytic process. Like a snapshot, the tattoo is a dialectic record of the mother-father relationship, of desires for closeness and distance, commonality and difference, identification and individuation. As Walter Benjamin famously stated about the nature of visual images in his Arcades Project, the tattoo represents "dialectics at a standstill." What seems paramount to the patient who participates in the act of tattooing is the need for stasis and immutability, as if bringing unconscious conflicts to "standstill" were to deliver a sense of stability. Unconsciously, the need is triggered by a threat to the inner stability resulting from fear of violating a taboo escalating to the point that fears of abandonment and fusion become unbearable. On the one hand, the tattoo is a visual symbolization of a taboo transgression; on the other hand, it activates the same through an act of self-injury that resembles the magical ritual acts of indigenous peoples' use of tattoos. The taboo thus serves as an ersatz for the actual violation of the taboo in real life, so that the tattoo may be ascribed a magical significance or totemic function. And yet the tattoo's success as a vehicle for constructing a transitional object is always contingent on the tangible manipulation of the skin conjoined with the creation of a symbolizing visual image. The image then acts like a "patch" to repair holes blown into Winnicott's "potential space" and to reconstruct it. PMID- 22320134 TI - Winnicott and Derrida: development of logic-of-play. AB - In this essay I develop the logic of play from the writings of the British psychoanalyst Donald W. Winnicott and the French philosopher Jacques Derrida. The logic of play serves as both a conceptual framework for theoretical clinical thinking and a space of experiencing in which the therapeutic situation is located and to which it aspires. I argue that both Winnicott and Derrida proposed a playful turn in Western thinking by their attitude towards oppositions, viewing them not as complementary or contradictory, but as 'peacefully-coexisting'. Derrida criticizes the dichotomous structure of Western thought, proposing playful movement as an alternative that does not constitute itself as a mastering construction. I will show that Winnicott, too, proposes playful logic through which he thinks and acts in the therapeutic situation. The therapeutic encounter is understood as a playful space in which analyst and analysand continuously coexist, instead of facing each other as exclusionary oppositions. I therefore propose the logic of play as the basis for the therapeutic encounter. The playful turn, then, is crucial for the thought and praxis expressed by the concept of two person psychology. I suggest the term playful psychoanalysis to characterize the present perspective of psychoanalysis in the light of the playful turn. I will first present Derrida's playful thought, go on to Winnicott's playful revolutionism, and conclude with an analysis of Winicott's clinical material in the light of the logic of play. PMID- 22320135 TI - What happens before and after acute enactments? An exercise in clinical validation and the broadening of hypotheses. AB - This paper seeks to validate clinical facts and theoretical hypotheses that have been discussed before and that address configurations involving chronic and acute enactments. Its validation process compares clinical material from psychoanalytic work in different psychoanalytic cultures - work from South America-Uruguay (Yardino), Europe-Spain (Sapisochin), South Africa (Ivey), Europe-UK (Bateman). It documents clinical facts described in four articles and confirms that during chronic enactments the analytic dyad gets caught up in a dual relationship that veils and congeals the triangular situation because acknowledging it would be traumatic. The lack of triangular space impedes the formation of symbols as well as dreaming and creates non-dreams-for-two. During chronic enactments analysts use their implicit alpha-function to assemble traumatic areas. These areas emerge as a mix of discharges and non-dreams that are dreamed through acute enactments. Acute enactments occur when chronic enactments dissolve and patients experience an abrupt contact with reality. The attenuated trauma is then dreamed alive. The linking of new symbols develops a network of symbolic thought and creates dreams for-two and broadens the patient's mental universe. The validation process has deepened our vision concerning clinical facts, especially in relation to: (1) the wavering between acute and chronic enactments, (2) analysts' inhibitions and feelings of guilt, and (3) the influence of analysts' personalities on the configurations they describe. These theoretical hypotheses have been confirmed and broadened not only in relation to the vicissitudes of dream work in traumatic areas, but also in relation to defenses such as thin or thick skin, and in relation to listening in countertransferential detours. PMID- 22320136 TI - Clinical issues in analyses over the telephone and the internet. AB - There is professional consensus that teleanalysis, the practice of psychoanalysis conducted remotely using the telephone and the Internet, is increasing in response to more mobility in the population. But there is controversy as to whether the use of technology leads to a dilution of analysis or to adaptive innovation that is clinically effective and true to the tenets of psychoanalysis. The author reviews the psychoanalytic literature and shows the development of analytic thinking about this technology-assisted practice of psychoanalysis. She summarizes analysts' perceptions and experiences of the advantages and disadvantages, and considers the indications and contra-indications. She focuses on the clinical concerns that arise in terms of the frame, resistance, and the development of analytic process through the unconscious communication of internal objects, unconscious fantasy, transference and countertransference. She gives vignettes from the analysis of a man with trauma-related depression to address the concerns raised and to support her argument that analysis using the telephone and the Internet is a viable, clinically effective alternative to traditional analysis where necessary. PMID- 22320137 TI - Comparing a narcissistic and an autistic retreat: 'looking through or at the window'. AB - In this paper I discuss two different forms of psychic retreats that I encountered in the treatment of a patient who suffered from two traumatic experiences: the loss of his mother when he was 2 years old and his 'near-death' experience when he was five. In the parasitic narcissistic retreat, using intensive projective identification enabled him to create an impasse in the form of a 'high tide - low tide' scenario in which alternating hope and disappointment kept the process going, yet paralyzed development. The autistic retreat, for its part, led to the collapse of projective identification mechanisms, dismantling and disrupting the transference/countertransference negotiations. The emerging state of non-communication and 'near death' seemed to act as a protection against the unbearable pain of abandonment and desolation. PMID- 22320138 TI - Fantasized recipient-donor relationships following lung transplantations: a qualitative case analysis based on patient narratives. AB - The present study examines the relationships between lung transplant recipients and their unknown, deceased donors. Out of 20 semi-structured interviews, eight narratives, by three female and three male recipients respectively, were identified in which the figure of the donor played a role. These narratives were examined using JAKOB, a qualitative research tool that analyses relational configurations and diagnoses psychodynamic conflicts. Analysis revealed a broad range of varying themes and relationships with equally varying wish and fear themes. All the narrators dealt either explicitly or implicitly with whether and how they are connected to their donors. In five narratives, specific personality traits were attributed to the figure of the donor; in four narratives, latent feelings of guilt concerning the donor's death were expressed. Indeed, the figure of the donor was not always perceived as an independent person, separate from the narrator's self: in two cases, the donor appears as part of the recipient's self, while in another case, the donor is presented as a transitional object for the recipient. The findings of the narrative analysis are discussed within a theoretical model of psychical organ integration. PMID- 22320139 TI - Affects in Melanie Klein. PMID- 22320140 TI - The ego according to Klein: return to Freud and beyond. AB - This paper explores fundamental dimensions of Melanie Klein's concept of the ego through a detailed study of the writings of Klein and her early colleagues (Paula Heimann, Susan Isaacs and Joan Riviere). The study examines three central issues: (a) the basic theoretical framework for Klein's conceptualization of the ego, and specifically how her conceptualization builds on Freud's structural and dual instinct models; (b) the processes involved in the development of the ego and its capacities (including the development from id to ego and from ego to superego); and (c) the view of the ego as an object of phantasy. Through this examination, the study demonstrates that Klein's conceptualization of the ego is firmly grounded both in Freud's formulations about the ego and in his theoretical and metapsychological approach to thinking about the ego. This counters the prevalent view that Klein was only focused on clinical understandings, unconcerned with theory and fuzzy in her abstract thinking. More specifically, it counters the view that Klein did not really have a concept of the ego in any well-structured sense of the term (Britton, 2003; Hinshelwood, 1994; Segal, 2001). The study considers the sources of these misconceived views. Finally, it argues that discarding such views allows us to appreciate better the richness of Klein's thinking, her theoretical affinities to Freud, and the role of theory in the development and justification of psychoanalysis. PMID- 22320141 TI - The thought of Hans W. Loewald. PMID- 22320142 TI - Infant observation and the French model. AB - Psychoanalytic training in the French Societies belonging to the International Psychoanalytic Association does not grant any place to the observation of babies as it exists in certain societies of other countries. Infant observation is even the object of sharp critiques by eminent French theoreticians. The reasons given for condemning infant observation and refusing to give it any place in the training programme lie in theoretical positions concerning the very nature of the Freudian discovery and its interpretation, which is more idealistic than empirical. The author discusses these reasons while drawing attention to the frequent confusion between a reference to empiricism and a reference to the experimental. The fear of a psychologizing deviation of metapsychology and of a denial of psychic reality leads, in the French model, to placing the emphasis on personal analytic experience during the candidate's psychoanalysis, prolonged by supervisions. It excludes any academic teaching of metapsychology or of related disciplines. The confusion between the empiricism of Esther Bick's method and the recourse to experimental procedures in developmental research stands in the way of making a place for infant observation and of recognizing its training value, not so much for the acquisition of new knowledge or the validation of metapsychological models, as for its usefulness in developing a mode of psychoanalytic observation and an increase in the candidates' containing capacities. PMID- 22320143 TI - Failures of the 'moral defence' in the films Shutter Island, Inception and Memento: narcissism or schizoid personality disorder? PMID- 22320144 TI - The European annuals of the International Journal of Psychoanalysis: the benefits of linguistic diversity. AB - This paper presents the Annuals of the International Journal of Psychoanalysis, which have been published in Europe since 2003, successively in French, Italian, German, Turkish and Russian. Like the Annuals published since 1985 in Latin America, these are designed to give non-Anglophone readers access to a selection of leading psychoanalytic articles. Each European Annual makes its own selection so the content varies from one Annual to another. Psychoanalysts on the various editorial committees translate the texts from English into their native target language on a voluntary basis. Beyond the geographical and cultural criteria, the desire to translate and the enjoyment of translating are among the key criteria. The Annual editors consider it important that the English language should continue to exist as a psychoanalytic lingua franca, without actually becoming its universal language, so that the richness and diversity of the psychoanalytic languages and terminologies can be preserved. The European Annuals in French, Italian, German, Turkish and Russian, with their linguistic and cultural characteristics, are then presented in turn. PMID- 22320145 TI - Increased cardiac troponin T levels are related to inflammatory markers and various indices of renal function in chronic renal disease patients. AB - BACKGROUND/OBJECTIVES: Cardiovascular disease begins early in the course of chronic kidney disease (CKD), and the glomerular filtration rate (GFR) is an independent risk factor for it. There is little information on cardiac troponin concentrations in patients with CKD who have not commenced dialysis. Factors associated with this deleterious process are not completely understood, and we aimed to determine associated laboratory abnormalities of increased cardiac troponin T (cTnT) in patients with CKD. METHODS: In this study, 104 patients (65 males and 39 females with mean age of 65 +/- 15 years) were recruited. A detailed clinical history was recorded and routine biochemical variables and cTnT levels were measured. GFR was estimated (44.62 +/- 14.38 mL/min/1.73 m(2)) using the modification of diet in renal disease study formula. RESULTS: cTnT is correlated with blood urea (r = 0.262, p < 0.05), uric acid (r = 0.399, p < 0.001), blood phosphorus (r = 0.550, p < 0.001), triglyceride (r = 0.329, p = 0.011), C reactive protein (CRP; r = 0.768, p < 0.001), renal resistive index (RRI; r = 0.412, p = 0.017), and GFR (r = -0.755, p = 0.011). On stepwise multiple regression analysis, increased CRP (>=12 mg/L), uric acid (>=5 mg/L), and RRI (>=0.70) were independent variables for increased cTnT status (r(2) = 0.053, p < 0.05). CONCLUSION: Increased cTnT not only shows ongoing inflammation but also is a sensitive marker of functioning renal mass. It is strongly correlated with factors influencing the decline in renal function; thus, it can be used as a renal risk parameter. PMID- 22320146 TI - Multilocus analysis of nucleotide variation in Drosophila madeirensis, an endemic species of the Laurisilva forest in Madeira. AB - Drosophila madeirensis is an endemic species of Madeira that inhabits the island Laurisilva forest. Nucleotide variation in D. madeirensis is analysed in six genomic regions and compared to that previously reported for the same regions in Drosophila subobscura, an abundant species in the Palearctic region that is closely related to D. madeirensis. The gene regions analysed are distributed along the O(3) inversion. The O(3) arrangement is monomorphic in D. madeirensis, and it was present in ancestral populations of D. subobscura but went extinct in this species after the origin of the derived O(ST) and O(3+4) arrangements. Levels of nucleotide polymorphism in D. madeirensis are similar to those present in the O(ST) and O(3+4) arrangements of D. subobscura, and the frequency spectrum is skewed towards rare variants. Purifying selection against deleterious nonsynonymous mutations is less effective in D. madeirensis. Although D. madeirensis and D. subobscura coexist at present in Madeira, no clear evidence of introgression was detected in the studied regions. PMID- 22320147 TI - The Renaissance Kidney-Nephrology in and about the Sixteenth Century. AB - The endeavor to understand the workings of the human body is as old as civilization; but it is in the intellectual movement of the Renaissance that its actual scientific study began in earnest and has not ceased growing since then. It was in the 16th century that the study of organs was launched and with it that of the kidney, which was then conceived as an accessory organ to clear the excess water ingested with food. The study of the structural basis of kidney function was launched by Bartolomeo Eustachio (1514-1574); the elements of its physiology and pathology were promulgated by Jean Fernel (1497-1558), and that of the chemical study of urine and of the principal cause of kidney disease then, calculi, instigated by Joan Baptista Van Helmont (1577-1644). The methodological approaches of these and their contemporary investigators, which were crystallized and formulated by Francis Bacon (1561-1626), opened the gates of the Scientific Revolution that followed in the 17th century, beginning with that of describing the circulation in 1628 by William Harvey (1564-1657) that would finally free the kidney from the shackles imposed on it as a mere accessory organ to the liver in Galen's physiology. PMID- 22320148 TI - Efficacy and safety of a 12-week treatment with twice-daily aclidinium bromide in COPD patients (ACCORD COPD I). AB - BACKGROUND: This Phase III study evaluated the efficacy and safety of twice-daily aclidinium 200 MUg and 400 MUg versus placebo in the treatment of moderate-to severe COPD. METHODS: In this 12-week, double-blind, multicenter trial, patients were randomized (1:1:1) to inhaled twice-daily aclidinium 200 MUg, aclidinium 400 MUg, or placebo. Primary and secondary endpoints were changes from baseline in trough FEV1 and peak FEV1 at Week 12, respectively. Health status (St. George's Respiratory Questionnaire [SGRQ]), COPD symptoms (Transitional Dyspnea Index [TDI], night and early morning symptoms), and safety were also assessed. RESULTS: A total of 561 patients (mean age, 64 +/- 9 years) with a mean baseline FEV1 of 1.36 +/- 0.54 L (47.2% of predicted value) were randomized. At Week 12, aclidinium 200 MUg and 400 MUg showed significant improvements from baseline in mean (95% CI) trough FEV1 compared with placebo by 86 (45, 127) mL and 124 (83,164) mL, respectively, and in peak FEV1 by 146 (101, 190) mL and 192 (148, 236) mL, respectively (p <= 0.0001 for all). Both aclidinium doses also provided significant improvements in SGRQ, TDI and almost all COPD symptom scores compared with placebo (p < 0.05 for all). Incidences of adverse events (AEs) were similar across treatment groups. The incidence of anticholinergic AEs was low and similar across groups (dry mouth: 0.5%-1.6%; constipation: 0%-1.1%). CONCLUSIONS: Treatment of moderate-to-severe COPD patients with twice-daily aclidinium 200 MUg and 400 MUg was associated with significant improvements in bronchodilation, health status, and COPD symptoms. Both doses were well tolerated and had safety profiles similar to placebo. TRIAL REGISTRATION: This ACCORD I study (AClidinium in Chronic Obstructive Respiratory Disease I) was registered on clinicaltrials.gov (NCT00891462) as "Efficacy and Safety of Aclidinium Bromide for Treatment of Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)". PMID- 22320149 TI - Integrating normal and abnormal personality structure: the Five-Factor Model. AB - It is evident that the conceptualization, diagnosis, and classification of personality disorder (PD) is shifting toward a dimensional model. The purpose of this special issue of Journal of Personality is to indicate how the Five-Factor Model (FFM) can provide a useful and meaningful basis for an integration of the description and classification of both normal and abnormal personality functioning. This introductory article discusses its empirical support and the potential advantages of understanding personality disorders, including those included within the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders and likely future PDs from the dimensional perspective of the FFM. PMID- 22320150 TI - Patient-practitioner-remedy: quantum interactions in living systems. PMID- 22320151 TI - On the applicability of elastic network normal modes in small-molecule docking. AB - Incorporating backbone flexibility into protein-ligand docking is still a challenging problem. In protein-protein docking, normal mode analysis (NMA) has become increasingly popular as it can be used to describe the collective motions of a biological system, but the question of whether NMA can also be useful in predicting the conformational changes observed upon small-molecule binding has only been addressed in a few case studies. Here, we describe a large-scale study on the applicability of NMA for protein-ligand docking using 433 apo/holo pairs of the Astex data sets. On the basis of sets of the first normal modes from the apo structure, we first generated for each paired holo structure a set of conformations that optimally reproduce its C(alpha) trace with respect to the underlying normal mode subspace. Using AutoDock, GOLD, and FlexX we then docked the original ligands into these conformations to assess how the docking performance depends on the number of modes used to reproduce the holo structure. The results of our study indicate that, even for such a best-case scenario, the use of normal mode analysis in small-molecule docking is restricted and that a general rule on how many modes to use does not seem to exist or at least is not easy to find. PMID- 22320152 TI - Silencing of connexin 43 suppresses invasion, migration and lung metastasis of rat hepatocellular carcinoma cells. AB - To reduce cancer mortality, understanding of mechanisms of cancer metastasis is crucial. We have established six rat hepatocellular carcinoma (HCC) cell lines, which exhibit differing metastatic potential to the lung after inoculation into the tail veins of nude mice. In the present experiment, we investigated the process of cell attachment to metastatic sites and possible regulating factors. One hour after inoculation, two of two HCC cell lines with high metastatic potential and one of two HCC cell lines with low metastatic potential exhibited many attached cells in the lung. One day after inoculation, lung metastatic foci were observed only with highly-metastatic cells with elevated connexin 43 (Cx43) expression as assessed by cDNA array analysis. Furthermore, 24 or 48 h after transfection of an siRNA targeting Cx43, in vitro invasion and migration were suppressed by 68% (P < 0.001) and 36% (P < 0.05) compared with control-siRNA transfected cells, despite no differences in cellular morphology, cell proliferation or apoptotic activity. Moreover, the number of metastatic nodules per lung area in nude mice was significantly (P < 0.01) reduced. In conclusion, suppression of Cx43 expression in tumor cells reduced in vitro migration and invasion capacity and in vivo metastatic ability so that Cx43 has potential as a molecular target for prevention of cancer metastasis with Cx43 overexpressing tumors. PMID- 22320153 TI - Using lean techniques to define the platelet (PLT) transfusion process and cost effectiveness to evaluate PLT dose transfusion strategies. AB - BACKGROUND: Platelet (PLT) doses of 1.1 * 10(11), 2.2 * 10(11), and 4.4 * 10(11) /m(2) body surface area are equally effective in preventing bleeding. These different dose strategies involve different numbers of transfusions. We conducted a cost analysis of three separate PLT dose therapies. STUDY DESIGN AND METHODS: A process map of preparation and administration of a PLT transfusion identified 46 steps (23 steps in the blood bank and 23 steps on the care unit). Time studies were conducted for these 46 steps. Supply costs and personnel costs were estimated based on time studies. We conducted a cost analysis of three separate treatment regimes involving 16 transfusions per patient for the low-dose, 12 transfusions for medium-dose, and eight transfusions for high-dose regimes. RESULTS: The time and the cost of the transfusion process for the blood bank were 32.41 minutes and $21.93 per unit, and for the patient care unit, 58.36 minutes and $57.71 per unit. The total cost for a course of PLT therapy per patient ranged from $4503.77 to $7014.59 for three different PLT doses. For a simulated bone marrow transplantation unit with 259 patients annually, there would be approximately a $700,000 difference among the clinically equivalent low-, medium , and high-dose treatment options. CONCLUSIONS: The overall cost of transfusion therapy is more influenced by the cost of the product than the cost of providing the transfusion. Depending on the cost adjustment by the supplier for different doses of PLTs, a low-dose transfusion strategy can be less costly. PMID- 22320154 TI - Nuclear translocation of pro-amphiregulin induces chemoresistance in gastric cancer. AB - Amphiregulin (AR) is derived from a membrane-anchored form (proAR) by ectodomain shedding, and is a ligand that activates epidermal growth factor receptor (EGFR). We have recently shown that proAR translocates from the plasma membrane to the nucleus after truncation of 11 amino acids at the C-terminus, which is independent of the conventional EGFR signaling pathway. Although proAR immunoreactivity has reportedly been detected in the nucleus of cancer cells, its biological meaning has never been investigated. This study was performed to investigate the roles of proAR nuclear translocation in human gastric cancer. We constructed proAR truncated 11 amino acids at the C-terminus (proARDeltaC11) that spontaneously translocates to the nucleus, and established proARDeltaC11 expression regulatable gastric cancer cells (MKN45, MKN28) using the tet-off system. Using these cells, we found that proAR nuclear translocation significantly induced chemoresistance in vitro and in vivo. Analyzing the relationship between immunoreactive localization of proAR and the clinical outcome for 46 advanced gastric cancer cases treated with chemotherapy, median survival time was 311 days in 16 patients with AR-positive staining in the nucleus and 387 days in 30 patients with AR-negative staining (P < 0.05). The present study demonstrates that proAR nuclear translocation increases resistance to anti-cancer drugs, which might be associated with poor prognosis in human gastric cancer. PMID- 22320155 TI - Cortisol release, heart rate and heart rate variability, and superficial body temperature, in horses lunged either with hyperflexion of the neck or with an extended head and neck position. AB - Bringing the head and neck of ridden horses into a position of hyperflexion is widely used in equestrian sports. In our study, the hypothesis was tested that hyperflexion is an acute stressor for horses. Salivary cortisol concentrations, heart rate, heart rate variability (HRV) and superficial body temperature were determined in horses (n = 16) lunged on two subsequent days. The head and neck of the horse was fixed with side reins in a position allowing forward extension on day A and fixed in hyperflexion on day B. The order of treatments alternated between horses. In response to lunging, cortisol concentration increased (day A from 0.73 +/- 0.06 to 1.41 +/- 0.13 ng/ml, p < 0.001; day B from 0.68 +/- 0.07 to 1.38 +/- 0.13 ng/ml, p < 0.001) but did not differ between days A and B. Beat-to beat (RR) interval decreased in response to lunging on both days. HRV variables standard deviation of RR interval (SDRR) and RMSSD (root mean square of successive RR differences) decreased (p < 0.001) but did not differ between days. In the cranial region of the neck, the difference between maximum and minimum temperature was increased in hyperflexion (p < 0.01). In conclusion, physiological parameters do not indicate an acute stress response to hyperflexion of the head alone in horses lunged at moderate speed and not touched with the whip. However, if hyperflexion is combined with active intervention of a rider, a stressful experience for the horse cannot be excluded. PMID- 22320157 TI - A bibliometric review of the Journal of Advanced Nursing, 1976-2010. PMID- 22320158 TI - Using disaster exercises to determine staff educational needs and improve disaster outcomes in rural hospitals: the role of the nursing professional development educator. AB - Using human potential in rural hospitals is vital to successful outcomes when handling disasters. Nursing professional development educators provide leadership and guiding vision during a time when few educational research studies demonstrate how to do so. This article explains the role of the rural nursing professional development educator as a disaster preparedness educator, facilitator, collaborator, researcher, and leader, using the American Nurses Association's Nursing Professional Development: Scope and Standards of Practice. PMID- 22320159 TI - Friends of nursing: a community of caring to promote excellence in nursing practice, education, and research. AB - More than 25 years ago, the name "Friends of Nursing" was adopted by an academic, community Magnet((r)) hospital to signify a model for community support of nursing. From inception, the intent was to recruit philanthropic dollars to promote recognition of and excellence in nursing practice, education, and research. Although philanthropy in health care settings is common, what is unique about this program is the long-standing, dedicated conceptual framework for nursing philanthropy and the very significant number of philanthropic dollars from literally thousands of donors to support a diverse range of activities to affect and advance the professional excellence of nurses and the quality of patient care. This model has been successfully replicated within a wide variety of other health care organizations and nursing services throughout the United States and abroad. PMID- 22320160 TI - The health and life priorities of individuals with spinal cord injury: a systematic review. AB - Determining the priorities of individuals with spinal cord injury (SCI) can assist in choosing research priorities that will ultimately improve their quality of life. This systematic review examined studies that directly surveyed people with SCI to ascertain their health priorities and life domains of importance. Twenty-four studies (a combined sample of 5262 subjects) that met the inclusion criteria were identified using electronic databases (Medline, EMBASE, CINAHL, and PsycINFO). The questionnaire methods and domains of importance were reviewed and described. While the questionnaires varied across studies, a consistent set of priorities emerged. Functional recovery priorities were identified for the following areas: motor function (including arm/hand function for individuals with tetraplegia, and mobility for individuals with paraplegia), bowel, bladder, and sexual function. In addition, health, as well as relationships, emerged as important life domains. The information from this study, which identified the priorities and domains of importance for individuals with SCI, may be useful for informing health care and research agenda-setting activities. PMID- 22320161 TI - Synthesis and characterization of beta-diketiminate germanium(II) compounds. AB - Reactions of LGeCl (L = CH[C(Me)N(Ar)](2); Ar = 2,6-iPr(2)C(6)H(3)) with KOtBu or LiR (R = 2-thienyl, N(H)Ar, PPh(2)) yielded the germanium(II) compounds LGeR [R = OtBu (1), 2-thienyl (2), N(H)Ar (3), PPh(2) (4)]. The reduction of (2 thienyl)(2)PCl with lithium afforded the diphosphane [(2-thienyl)(2)P](2) (5). The treatment of (2-thienyl)(2)PCl with LiAlH(4) or KHBtBu(3) led to the formation of (2-thienyl)(2)PH (6). The NHC-assisted reaction of LGeCl and 6 resulted in the isolation of LGeP(2-thienyl)(2) (7). This is the first example where NHC is used for eliminating HCl from compounds with P-H and Ge-Cl bonds. All solid products were characterized by elemental analysis, NMR and IR spectroscopy, and single-crystal X-ray structure determination. PMID- 22320162 TI - Chemobioinformatics: the advancing frontier of computer-aided drug design in the post-genomic era. PMID- 22320163 TI - Steroids and phenolic constituents from the fruiting bodies of the basidiomycete Sarcodon joedes. AB - Nine secondary metabolites, including four steroids, four phenolics and one cerebroside, were isolated from the methanol extract of the fruiting bodies of the basidiomycete Sarcodon joedes. The isolated compounds were identified by spectroscopic analyses as (22E,24R)-6beta-methoxyergosta-7,22-diene-3beta,5alpha diol (1), 2',3'-diacetoxy-3,4,5',6',4"-pentahydroxy-p-terphenyl (2), cerebroside B (3), ergosta-7,22-dien-3beta-ol (4), ergosterol peroxide (5), (22E,24R)-3beta hydroxy-ergosta-5,22-dien-7-one (6), benzoic acid (7), methyl p-hydroxybenzoate (8) and 3,4-dihydroxybenzoic acid (9). The cytotoxic activities of these compounds were evaluated. All these compounds were isolated from this fungus for the first time. PMID- 22320164 TI - Real-time droplet DNA amplification with a new tablet platform. AB - We present a novel droplet-based tablet platform for temporal polymerase chain reaction (PCR) in microliter droplets. The simple design of the device does not require extensive processing or external equipment, which allows for greater ease of use and integration as a point-of-care diagnostic. We demonstrate its functionality to perform both PCR and reverse-transcription PCR for lambda phage DNA and H3 influenza RNA with ramp rates and cycle times consistent with traditional PCR thermal cyclers. We additionally investigate the effect of performing PCR in small volumes on the reaction performance by specifically examining adsorption of reagents at the oil/water interface. We determined that adsorption of Taq polymerase at the biphasic interface reduces yield and impairs reaction performance at standard concentrations. Thus, microdroplet PCR reactions require additional polymerase to achieve sufficient amplification and we project for applications utilizing nanodroplets or picodroplets like digital applications, even greater concentrations of polymerase are required to achieve desired results. Following the adsorption investigation, we evaluated the sensitivity of lambda phage PCR on our platform to be less than 2.0 copies/MUL with an efficiency of 104.4% and similar sensitivity for reverse-transcription PCR for influenza H3 RNA. PMID- 22320165 TI - Hepatoprotective effects of S-adenosylmethionine and silybin on canine hepatocytes in vitro. AB - Inflammation and oxidative stress are associated with liver injury and development of liver disease. The transcription factors nuclear factor-kappa beta (NF-kappaB) and nuclear factor erythroid 2-related factor 2 (Nrf2) play critical roles in modulating liver injury and damage. Activation of NF-kappaB induces production of pro-inflammatory molecules including prostaglandin E2 (PGE2 ), interleukin-8 (IL-8) and macrophage chemotactic protein-1 (MCP-1). Nrf2 regulates genes controlling antioxidants. Our laboratory previously showed that hepatocytes, the primary functional cell type comprising liver tissue, respond to the cytokine interleukin-1 beta (IL-1beta) by increased production of PGE2 , IL-8 and MCP-1. This increase is associated with nuclear translocation of NF-kappaB. In this study, we evaluated whether primary canine hepatocytes pre-treated with the combination of S-adenosylmethionine (SAMe; 30 and 2000 ng/ml) and silybin (SB; 298 ng/ml), agents with known anti-inflammatory and antioxidant properties, could attenuate IL-1beta-induced inflammation and oxidative stress. The SAMe and SB combination reduced cytokine-induced PGE2 , IL-8 and MCP-1 production while also inhibiting NF-kappaB nuclear translocation. These changes were accompanied by increased antioxidant enzyme-reduced glutathione (GSH) comparable to control levels. The study shows for the first time that the SAMe and SB combination inhibits both inflammation and oxidative stress through two separate signalling pathways. PMID- 22320166 TI - Visual monitoring of solid-phase extraction using chromogenic fluorous synthesis supports. AB - Reductive aminations and further transformations of an azo dye and fluorous tagged aldehyde are described. The intensely colored 2,4-dialkoxybenzyl protected amines undergo Fmoc-based peptide coupling, Suzuki reactions, and sulfonamide formation with product isolation facilitated by visual monitoring of fluorous solid phase extraction. Target compounds are released from the supports in high yields and purities by treatment with trifluoroacetic acid (TFA). PMID- 22320167 TI - A case of Spider bite localized to the eyelid. AB - Loxosceles Spiders have a worldwide distribution and are considered one of the most medically important groups of Spiders. The venom from Spiders of the genus Loxosceles, the most famous being Loxosceles reclusa (brown recluse Spider), can promote severe local and systemic damages. This report describes a girl presenting with a Spider bite over her right upper eyelid. PMID- 22320168 TI - Comparative assessment of the global fate of alpha- and beta hexachlorocyclohexane before and after phase-out. AB - Technical hexachlorocyclohexane (HCH) was one of the most widely used pesticides during the 20th century. Although production and use were phased-out during the 1990s, two of its major components, alpha- and beta-HCH, are still ubiquitous in the environment. Here, we have collected and analyzed data on concentrations of alpha- and beta-HCH in the atmosphere and oceans, including spatial and temporal trends and seasonalities. We apply a global fate and transport model to both isomers over the period 1950 to 2050 to rationalize current levels and trends at remote locations with estimated emissions and to forecast into the near future. Our model results indicate that secondary emissions from soils and oceans are currently controlling the observed rates of decline in the atmosphere. beta-HCH is declining more slowly than alpha-HCH due to its higher persistence, and we hypothesize that it will eventually become the predominant isomer of HCH in the environment. The model reproduces over 70% of measured concentrations of alpha HCH in air and ocean water within factors of 3 and 5, respectively, and over 70% of measured concentrations of beta-HCH within factors of 8 and 20, respectively. The model results are only weakly sensitive to climate change-induced trends in Arctic sea-ice cover and temperature. PMID- 22320169 TI - Utilizing mobile networks for the detection of clinically relevant interactions between chemotherapy regimens and complementary and alternative medicines. AB - OBJECTIVES: Patients with cancer who use complementary and alternative medicines (CAMs) in conjunction with chemotherapy treatment are at risk of manifesting anticancer drug-CAM interactions (DCIs), which may lead to negative therapeutic outcomes. This article describes a novel iPhone application developed for the Mobile Internet, called OncoRx-MI, which identifies DCIs of single-agent and multiple-agent chemotherapy regimen (CReg) prescriptions. METHODS: Drug-, CAM-, and DCI-related information was compiled from various hardcopy and softcopy sources, and published literature from PubMed. Overall management plans for the CRegs were then developed. The iPhone Web documents were constructed using Adobe software and programming scripts, and mounted onto a third-party server. DCI searches are based on CReg acronyms, and OncoRx-MI is designed to fit the iPhone screen configuration for improved usability. A small usability study was also carried out and the user feedback presented. RESULTS: OncoRx-MI is able to detect over 2700 interactions between 256 CRegs and 166 CAMs, making up a total of over 4400 DCI pairs. The CAMs are classified into seven categories based on their uses in supportive care, and non-cancer-related CAMs are also included. The majority of the DCIs are pharmacokinetic in nature (79%), involving the induction and inhibition of the cytochrome P450 isozymes and p-glycoprotein. Pharmacodynamic DCIs include hepatotoxicity (39%), altered corticosteroid efficacies (30%), and increased risks of hypoglycemia (4%), hypertensive crisis (2%), bleeding, and serotonin syndrome (1% each). CONCLUSIONS: OncoRx-MI is the first mobile application of its kind that allows searching of DCIs for CRegs through 3G networks, and is intended to improve pharmaceutical care of patients with cancer by assisting health care practitioners in managing CReg interactions in their clinical practices. PMID- 22320170 TI - Treatment of burns with burns & wounds (B & W) ointment and leaf therapy. PMID- 22320171 TI - An unusual case of renal failure due to solitary plasmacytoma: parenchymal invasion of the kidney. AB - Solitary extramedullary plasmacytoma (EMP) is a rare plasma cell disorder mostly involving the upper airway; however, retroperitoneal infiltration is very rare. Kidney injury associated with EMP is exceptionally rare with only anecdotal reports. Herein we report a case of retroperitoneal EMP causing renal failure by the way of direct renal parenchymal infiltration. Renal parenchymal invasion should be considered in aggressive and refractory plasma cell dyscrasias with unexplained renal failure. PMID- 22320172 TI - Proton grease: an acid accelerated molecular rotor. AB - A molecular rotor was designed that rotates 7 orders of magnitude faster upon protonation. The quinoline rotor is based on a rigid N-arylimide framework that displays restricted rotation due to steric interaction between the quinoline nitrogen and imide carbonyls. At rt (23 degrees C), the rotor rotates slowly (t(1/2) = 26 min, DeltaG(?) = 22.2 kcal/mol). However, upon addition of 3.5 equiv of acid the rotor rotates rapidly (t(1/2) = 2.0 * 10(-4) s, DeltaG(?) = 12.9 kcal/mol). Mechanistic studies show that this dramatic acid catalyzed change is due to stabilization of the planar transition state by the formation of an intramolecular hydrogen bond between the protonated quinoline nitrogen (N(+)-H) and an imide carbonyl (O?C). The acid catalyzed acceleration is reversible and can be stopped by addition of base. PMID- 22320173 TI - Learning in a web of commitments. AB - Drawing on interviews and survey results from a national study of nursing education, this article discusses student learning related to professional responsibilities. It explores what is missing when students do not have the opportunity to reflect on the multiple commitments they will meet in nursing. Inspired by the moral philosopher Larry May's communitarian approach, we suggest students must learn a broad notion of professional responsibility. We demonstrate reasons why students need the opportunity to reflect on issues concerning the civic, moral, and societal dimensions of professional responsibility. We also indicate ways for students to reflect as part of their educational experience. PMID- 22320174 TI - Teaching in a web of commitments. AB - Drawing on interviews and survey results from a national study of nursing education, this article discusses teaching professional responsibilities in prelicensure nursing education and explores how to help students reflect on multiple commitments they will meet in nursing. Inspired by the moral philosopher Larry May's communitarian approach, we suggest strategies for teaching students a broad notion of professional responsibility, including the profession's moral and societal responsibilities. PMID- 22320175 TI - The lived experience of non-degree learners from a time-modified traditional baccalaureate nursing program. AB - An emerging trend to temper the nursing shortage is to accelerate the pace of traditional 4-year baccalaureate programs, with minimal curricular or programmatic changes, which we refer to as a Time-Modified Traditional Program (TMTP) study. Many students enrolled in a TMTP reflect the characteristics of entry-level, traditional nursing students. The purpose of this study was to gain an understanding of how those non-degree, traditional baccalaureate nursing students experience education in a TMTP. Van Manen's six research activities of hermeneutic phenomenology guided this study. Colaizzi's seven-step method was used for analyzing the research data. Eight main themes were identified that provide a description of the phenomenon. Due to the intensity and time requirements of the program, students become disengaged from their previous lifestyles and relationships. Building a strong support system with faculty and peers and assuming personal accountability for learning contributes to the overall success of the program. PMID- 22320176 TI - Shifting the clinical teaching paradigm in undergraduate nursing education to address the nursing faculty shortage. AB - To address the faculty shortage problem, schools of nursing are reexamining how they provide clinical education to undergraduate students to find ways to use faculty resources more efficiently and to maintain student enrollment. We describe a unique clinical teaching model implemented at the New York University College of Nursing. The new model currently being evaluated shifts from the traditional clinical education model, in which all clinical education is in a hospital or agency setting, to a model that substitutes high-fidelity human patient simulation for up to half of the clinical education experience. This article describes the clinical teaching model and its effects on nurse faculty capacity. PMID- 22320177 TI - Ferromagnetism in graphene nanoribbons: split versus oxidative unzipped ribbons. AB - Two types of graphene nanoribbons: (a) potassium-split graphene nanoribbons (GNRs), and (b) oxidative unzipped and chemically converted graphene nanoribbons (CCGNRs) were investigated for their magnetic properties using the combination of static magnetization and electron spin resonance measurements. The two types of ribbons possess remarkably different magnetic properties. While a low-temperature ferromagnet-like feature is observed in both types of ribbons, such room temperature feature persists only in potassium-split ribbons. The GNRs show negative exchange bias, but the CCGNRs exhibit a "positive exchange bias". Electron spin resonance measurements suggest that the carbon-related defects may be responsible for the observed magnetic behavior in both types of ribbons. Furthermore, information on the proton hyperfine coupling strength has been obtained from hyperfine sublevel correlation experiments performed on the GNRs. Electron spin resonance finds no evidence for the presence of potassium (cluster) related signals, pointing to the intrinsic magnetic nature of the ribbons. Our combined experimental results may indicate the coexistence of ferromagnetic clusters with antiferromagnetic regions leading to disordered magnetic phase. We discuss the possible origin of the observed contrast in the magnetic behaviors of the two types of ribbons studied. PMID- 22320178 TI - Hox gene evolution: multiple mechanisms contributing to evolutionary novelties. AB - Hox genes, which are important for determining regional identity in organisms as diverse as flies and humans, are typically considered to be under strong evolutionary constraints because large changes in body plan are usually detrimental to survival. Despite this, there is great body plan diversity in nature, and many of the mechanisms underlying this diversity have been attributed to changes in Hox genes. Over the past year, several studies have examined how Hox genes play a role in evolution of body plans and novelties. Here, we examine four distinct evolutionary mechanisms implicated in Hox gene evolution, which include changes in (1) Hox gene expression, (2) downstream Hox target gene regulation without change in Hox expression, (3) protein-coding sequence, and (4) posttranscriptional regulation of Hox gene function. We discuss how these types of changes in Hox genes--once thought to be evolutionarily static--underlie morphological diversification. We review recent studies that highlight each of these mechanisms and discuss their roles in the evolution of morphology and novelties. PMID- 22320179 TI - Computer-aided molecular design of asymmetric pyrazole derivatives with exceptional enantioselective recognition toward the Chiralcel OJ-H stationary phase. AB - A computer-aided design of novel asymmetric pyrazoles with improved enantioselective properties was performed by docking experiments starting from a model of Chiralcel OJ chiral in the stationary phase. Synthesis and HPLC experiments confirmed the theoretical prediction and led to a detailed investigation of the enantioselective recognition process. For the first time, looking at the time spent by each enantiomer in contact with the CSP during long molecular dynamic simulations, the experimental analytical trend has been reproduced. PMID- 22320180 TI - The red queen coupled with directional selection favours the evolution of sex. AB - Why sexual reproduction has evolved to be such a widespread mode of reproduction remains a major question in evolutionary biology. Although previous studies have shown that increased sex and recombination can evolve in the presence of host parasite interactions (the 'Red Queen hypothesis' for sex), many of these studies have assumed that multiple loci mediate infection vs. resistance. Data suggest, however, that a major locus is typically involved in antigen presentation and recognition. Here, we explore a model where only one locus mediates host-parasite interactions, but a second locus is subject to directional selection. Even though the effects of these genes on fitness are independent, we show that increased rates of sex and recombination are favoured at a modifier gene that alters the rate of genetic mixing. This result occurs because of selective interference in finite populations (the 'Hill-Robertson effect'), which also favours sex. These results suggest that the Red Queen hypothesis may help to explain the evolution of sex by contributing a form of persistent selection, which interferes with directional selection at other loci and thereby favours sex and recombination. PMID- 22320181 TI - Inhibition of airway hyper-responsiveness by TRPV1 antagonists (SB-705498 and PF 04065463) in the unanaesthetized, ovalbumin-sensitized guinea pig. AB - BACKGROUND AND PURPOSE Airway sensory nerves play a key role in respiratory cough, dyspnoea, airway hyper-responsiveness (AHR), all fundamental features of airway diseases [asthma and chronic obstructive pulmonary disease (COPD)]. Vagally mediated airway reflexes such as cough, bronchoconstriction and chest tightness originate from stimulation of airway sensory nerve endings. The transient receptor potential vanilloid 1 receptor (TRPV1) is present on peripheral terminals of airway sensory nerves and modulation of its activity represents a potential target for the pharmacological therapy of AHR in airway disease. EXPERIMENTAL APPROACH As guinea pig models can provide some of the essential features of asthma, including AHR, we have established the model with some classical pharmacological agents and examined the effect of the TRPV1 antagonists, SB-705498 and PF-04065463 on AHR to histamine evoked by ovalbumin (OA) in unanaesthetized sensitized guinea pigs restrained in a double chamber plethysmograph. Specific airway conductance (sGaw) derived from the airflow was calculated as a percentage of change from baseline. KEY RESULTS Cetirizine and salbutamol significantly inhibited OA-evoked bronchoconstriction [sGaw area under the curve (AUC): 70 and 78%, respectively]. Atropine, SB-705498 and PF-04065463 significantly inhibited OA-evoked AHR to histamine in unanaesthetized, OA sensitized guinea pigs (sGaw AUC: 94%, 57% and 73%, respectively). Furthermore, this effect was not related to antagonism of histamine's activity. CONCLUSION AND IMPLICATIONS These data suggest that TRPV1 receptors located on airway sensory nerves are important in the development of AHR and that modulation of TRPV1 receptor activity represents a potential target for the pharmacological therapy of AHR in airway disease. PMID- 22320182 TI - Fluoride content in toothpastes commercialized for children in Chile and discussion on professional recommendations of use. AB - BACKGROUND: In Chile, no information is available regarding the soluble fluoride (F) content in the toothpastes commercialized for children and the country's guidelines recommend the use of F in toothpastes in an age-dependent concentration. No global consensus has been reached on this subject. AIM: To determine the soluble F concentration in dentifrices for children sold in Chile and to discuss Chilean guidelines and professional recommendations of use. DESIGN: Three samples of twelve different dentifrices were purchased from drugstores. Toothpastes were analysed in duplicate using an ion-specific electrode. The concentrations of total F (TF) and total soluble F (TSF) were determined (MUg F/g). RESULTS: Measured TF was consistent with that declared by the manufacturer in eight products. Two dentifrices showed lower TF and two higher F concentrations than declared. A toothpaste, marketed as low-F (450 ppm), showed F concentration threefold higher. Most dentifrices exhibited TSF concentrations similar to the TF content, except one sample that displayed considerably lower TSF than TF. Recommendations on F toothpastes use in children widely vary from country to country. CONCLUSIONS: Most dentifrices for children match F content in the labelling, but recommendations are not supported by the best evidence available on the benefit/risk of F toothpastes use. PMID- 22320184 TI - Maladaptively high and low openness: the case for experiential permeability. AB - The domain of Openness within the Five-Factor Model (FFM) has received inconsistent support as a source for maladaptive personality functioning, at least when the latter is confined to the disorders of personality included within the American Psychiatric Association's (APA) Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR; APA, ). However, an advantage of the FFM relative to the DSM-IV-TR is that the former was developed to provide a reasonably comprehensive description of general personality structure. Rather than suggest that the FFM is inadequate because the DSM-IV-TR lacks much representation of Openness, it might be just as reasonable to suggest that the DSM-IV-TR is inadequate because it lacks an adequate representation of maladaptive variants of both high and low Openness. This article discusses the development and validation of a measure of these maladaptive variants, the Experiential Permeability Inventory. PMID- 22320183 TI - Pericellular pH homeostasis is a primary function of the Warburg effect: inversion of metabolic systems to control lactate steady state in tumor cells. AB - The Warburg effect describes a heightened propensity of tumor cells to produce lactic acid in the presence or absence of O(2) . A generally held notion is that the Warburg effect is related to energy. Using whole-genome, proteomic MALDI-TOF MS and metabolite analysis, we investigated the Warburg effect in malignant neuroblastoma N2a cells. The findings show that the Warburg effect serves a functional role in regulating acidic pericellular pH (pHe), which is mediated by metabolic inversion or a fluctuating dominance between glycolytic-rate substrate level phosphorylation (SLP) and mitochondrial (mt) oxidative phosphorylation (OXPHOS) to control lactic acid production. The results also show that an alkaline pHe caused an elevation in SLP/OXPHOS ratio (approximately 98% SLP/OXPHOS); while the ratio was approximately 56% at neutral pHe and approximately 93% in acidic pHe. Acidic pHe paralleled greater expression of mitochondrial biogenesis and OXPHOS genes, such as complex III-V (Uqcr10, Atp5 and Cox7c), mt Fmc1, Romo1, Tmem 173, Tomm6, aldehyde dehydrogenase, mt Sod2 mt biogenesis component PPAR-gamma co-activator 1 adjunct to loss of mt fission (Mff). Moreover, acidic pHe corresponded to metabolic efficiency evidenced by a rise in mTOR nutrient sensor GbetaL, its downstream target (Eif4ebp1), insulin modulators (Trib3 and Fetub) and loss of catabolic (Hadhb, Bdh1 and Pygl)/glycolytic processes (aldolase C, pyruvate kinase, Nampt and aldose reductase). In contrast, alkaline pHe initiated loss of mitofusin 2, complex II IV (Sdhaf1, Uqcrq, Cox4i2 and Aldh1l2), aconitase, mitochondrial carrier triple repeat 1 and mt biosynthetic (Coq2, Coq5 and Coq9). In conclusion, the Warburg effect might serve as a negative feedback loop that regulates the pHe toward a broad acidic range by altering lactic acid production through inversion of metabolic systems. These effects were independent of changes in O(2) concentration or glucose supply. PMID- 22320185 TI - Cytologic and immunohistochemical characterization of a primitive neuroectodermal tumor in the brain of a dog. AB - A 6-year-old intact female Pointer dog was presented for evaluation of acute onset of ataxia, circling, and head tilt. Neurologic assessment revealed overall decreased postural reaction, left-sided hemiparesis with incoordination, rigidity of fore- and hindlimbs, strabismus of the right eye, and bilateral horizontal nystagmus. Using magnetic resonance imaging, a mass lesion was identified in the cerebrum adjacent to the left side of the cerebellum compressing the brain stem ventrally. The mass was incompletely resected, and during surgery fine-needle aspiration and biopsy of the mass were performed. Cytologically, smears were highly cellular and contained predominantly small to medium-sized discrete round cells with high nuclear to cytoplasmic ratios and round nuclei with rare deep clefts or indentation, smooth chromatin, and indistinct nucleoli. Numerous cytoplasmic fragments were noted in the background. The primary diagnosis was lymphoma; other differential diagnoses included neuroendocrine tumor and poorly differentiated tumor of neural origin. The histologic diagnosis was lymphoma, and the lesion was presumed to be metastatic. On immunohistochemical analysis, the cells expressed neither CD3 nor CD79a. Re-examination of the histologic section revealed disorganized sheets of cells with multifocal palisading and perivascular arrangements of rosette-like structures. An expanded panel of antibodies to vimentin, cytokeratin, glial fibrillary acid protein (GFAP), neuron-specific enolase (NSE), synaptophysin (SYN), S-100, and CD45 was applied to histologic sections. Neoplastic cells were immunoreactive for vimentin, NSE, and S-100. Based on the histologic appearance and immunophenotype of the tumor, a diagnosis of primitive neuroectodermal tumor (PNET) was made. PNET, although rare in dogs, should be considered as a differential diagnosis for round cell tumors in the brain. PMID- 22320186 TI - Effects of myocardial postconditioning on the recruitment of endothelial progenitor cells. AB - BACKGROUND: Ischemic postconditioning (PostC), brief repetitive cycles of ischemia and reperfusion during early reperfusion, is suggested to protect the myocardium in patients with stent thrombosis-elevation myocardial infarction (STEMI) by improved endothelial dysfunction and alteration of cytokine release. These mechanisms are also of importance for the recruitment of endothelial progenitor cells (EPC), an endogenous repair mechanism for re-endothelialization and neoangiogenesis. The aim of this study was to investigate the effect of PostC on recruitment of EPC. METHODS: EPC were analyzed in 20 patients with STEMI randomized to receive four cycles of PostC following percutaneous coronary intervention (PCI) or conventional PCI. Different subpopulations of EPC were quantified immediately and on day 4 using flow cytometry. Myocardium at risk, and infarct size was determined by cardiovascular magnetic resonance. RESULTS: There was no influence of PostC on the number of different EPC (CD34(+) , CD133(+) , CD34(+) CD133(+) , CD34(+) KDR(+) , CD34(-) CD133(+) KDR(+) , CD34(+) CD133(+) KDR(+) ). Left ventricular ejection fraction, myocardium at risk, and infarct size did not correlate to the mobilization of EPC. There was an inverse correlation between the symptom-to-balloon time and the mobilization of progenitor precursor cells (CD34(+) cells: R =-0.527, P = 0.02; CD133(+) cells: R =-0.624, P = 0.004; CD34(+) CD133(+) cells: R =-0.466, P = 0.04). DISCUSSION: Ischemic PostC did not result in improved mobilization of EPC in STEMI patients. The recruitment of progenitor cells seems to be related to the duration of ischemia rather than the size of the ischemic myocardial area. More effort is needed to understand the changes of endothelial surface markers by PostC and their role in EPC recruitment and homing. PMID- 22320187 TI - Syntheses, structures, and magnetic analyses of a family of heterometallic hexanuclear [Ni4M2] (M = Gd, Dy, Y) compounds: observation of slow magnetic relaxation in the Dy(III) derivative. AB - We described the syntheses, crystal structures, and magnetic behavior of a novel series of heterometallic [Ni(4)M(2)] [M = Gd (1), Dy (2) and Y (3)] hexanuclear compounds afforded by the reaction of rare-earth(III) nitrate, nickel(II) acetate, and Schiff-base ligand 2-(2-hydroxy-3-methoxybenzylideneamino)phenol (H(2)L) in a mixture of ethanol and dichloromethane in the presence of triethylamine. Single-crystal X-ray diffraction measurements reveal that all three compounds have a metal core made up of two Ni(2)MO(4) defective cubanes. The magnetic properties of all compounds have been studied. Solid-state direct current magnetic susceptibility analyses demonstrate competing antiferromagnetic and ferromagnetic interactions within both compounds 1 and 3. Solid-state alternating-current magnetic susceptibility investigations show a frequency dependent out-of-phase signal for compound 2 below 4 K, suggestive of slow magnetic relaxation. PMID- 22320188 TI - Polymerase chain reaction-based tests for pan-species and species-specific detection of human Plasmodium parasites. AB - BACKGROUND: There is still a need to improve the sensitivity of polymerase chain reaction (PCR) tests for malaria to detect submicroscopic asexual stage Plasmodium infections during the early phase and chronic, asymptomatic phase of infection when the parasite burden is very low. STUDY DESIGN AND METHODS: The inhibitory effect of hemoglobin (Hb) on PCR limits the volume of blood that can be used in the PCR-based detection of intraerythrocytic Plasmodium parasites. We lysed red blood cells with saponin to reduce the Hb concentration in extracted nucleic acid and, as a result, significantly increased the volume of blood that can be tested by PCR. The analytical sensitivity of the PCR was determined using whole blood spiked with ring-stage Plasmodium falciparum parasites, and its clinical sensitivity by testing blood film-positive and blood film-negative samples from individuals living in an endemic area in Ghana. RESULTS: We have developed a pan-Plasmodium PCR that detects all five human Plasmodium species with the highest analytical sensitivity of two P. falciparum parasites/mL of whole blood and species-specific PCR tests that distinguished between the five human Plasmodium species. Pan-Plasmodium PCR detected 78 of 78 (100%) blood film positive and 19 of 101 (18.81%) blood film-negative samples from asymptomatic individuals living in Ghana. Pan-Plasmodium PCR was equally sensitive with samples collected as anticoagulated whole blood and clotted blood and in blood collected by finger stick into capillaries. CONCLUSION: We have developed PCR tests with the highest reported sensitivity to date for pan-Plasmodium diagnosis and species-specific diagnosis and detected blood film-negative asymptomatic infections in individuals living in malaria-endemic countries. PMID- 22320189 TI - Polymorphisms of the vascular endothelial growth factor gene and severe radiation pneumonitis in non-small cell lung cancer patients treated with definitive radiotherapy. AB - Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis and lung cancer progression. We hypothesized that VEGF polymorphisms may modulate the risk of radiation pneumonitis (RP) in non-small cell lung cancer (NSCLC) patients treated with definitive radiotherapy. We genotyped three potentially functional VEGF single nucleotide polymorphisms (-460 T > C [rs833061], -634 G > C [rs2010963] and +936 C > T [rs3025039]) and estimated the associations of their genotypes and haplotypes with severe radiation pneumonitis (RP >=grade 3) in 195 NSCLC patients. We found that the VEGF genotypes of rs2010963 and rs3025039 single nucleotide polymorphisms as well as the -460C/-634G/+936C haplotype were predictors of RP development (adjusted hazard ratio [adjHR] = 2.33, 95% confidence interval [CI], 1.01-5.37, P = 0.047 for CC vs GG genotypes; adjHR = 28.13, 95% CI, 5.24-151.02, P < 0.001 for TT vs CC genotypes; and adjHR = 2.51, 95% CI, 1.27-4.98, P = 0.008 for T-C-T vs C-G-C haplotypes). In addition, there was a trend towards reduced RP risk in patients carrying an increased number of protective VEGF genotypes. Our data suggest that VEGF polymorphisms can modulate the risk of radiation pneumonitis in NSCLC patients treated with definitive radiotherapy. Large and independent studies are needed to confirm our findings. PMID- 22320190 TI - Adsorption of acetaldehyde on ice as seen from computer simulation and infrared spectroscopy measurements. AB - Detailed investigation of the adsorption of acetaldehyde on I(h) ice is performed under tropospheric conditions by means of grand canonical Monte Carlo computer simulations and compared to infrared spectroscopy measurements. The experimental and simulation results are in a clear accordance with each other. The simulations indicate that the adsorption process follows Langmuir behavior in the entire pressure range of the vapor phase of acetaldehyde. Further, it was found that the adsorption layer is strictly monomolecular, and the adsorbed acetaldehyde molecules are bound to the ice surface by only one hydrogen bond, typically formed with the dangling H atoms at the ice surface, in agreement with the experimental results. Besides this hydrogen bonding, at high surface coverages dipolar attraction between neighboring acetaldehyde molecules also contributes considerably to the energy gain of the adsorption. The acetaldehyde molecules adopt strongly tilted orientations relative to the ice surface, the tilt angle being scattered between 50 degrees and 90 degrees (i.e., perpendicular orientation). The range of the preferred tilt angles narrows, and the preference for perpendicular orientation becomes stronger upon saturation of the adsorption layer. The CH(3) group of the acetaldehyde molecules points as straight away from the ice surface within the constraint imposed by the tilt angle adopted by the molecule as possible. The heat of adsorption at infinitely low coverage is found to be -36 +/- 2 kJ/mol from the infrared spectroscopy measurement, which is in excellent agreement with the computer simulation value of -34.1 kJ/mol. PMID- 22320191 TI - Association between traumatic brain injury and the subsequent risk of brain cancer. AB - This population-based study in Taiwan aimed to investigate the risk of having a diagnosis of malignant brain tumors within 3 years after a traumatic brain injury (TBI). This study used data from the Traumatic Brain Injury Registry and the National Health Insurance Research Database. The study cohort comprised 5007 patients who had visited ambulatory care centers or had been hospitalized with a diagnosis of TBI between 2001 and 2002. The comparison cohort was 25,035 randomly selected enrollees. Each patient's brain cancer status was individually tracked for a 3-year period following their index date. Stratified Cox proportional hazards regressions were performed for analyses. During the 3 years of follow-up, nine patients in each cohort, both the TBI and the non-TBI cohort, were diagnosed with brain cancer. As compared to those patients without TBI, patients with TBI were more likely to receive a diagnosis of malignant brain tumors within the 3 year period following their index date: the incidence rate of malignant brain tumors was 6.28 (95% CI: 3.06-11.53) per 10,000 person-years in patients with TBI and 1.25 (95% CI: 0.61-2.29) per 10,000 person-years in patients without TBI. After adjusting for sociodemographic characteristics, the hazard of being diagnosed with malignant brain tumors during the 3-year follow-up period was 4.67 (95% CI: 1.84-11.83) times greater for those who sustained a TBI than for patients in the comparison cohort. In addition, we found an association between TBI severity and malignant brain tumor among patients with TBI (p=0.033). Our findings suggest a positive correlation between TBI and the relatively short-term development of malignant neoplasms of the brain. PMID- 22320192 TI - Hopelessness as a predictor of attempted suicide among first admission patients with psychosis: a 10-year cohort study. AB - Little is known about the longitudinal relationship of hopelessness to attempted suicide in psychotic disorders. This study addresses this gap by assessing hopelessness and attempted suicide at multiple time-points over 10 years in a first-admission cohort with psychosis (n = 414). Approximately one in five participants attempted suicide during the 10-year follow-up, and those who attempted suicide scored significantly higher at baseline on the Beck Hopelessness Scale. In general, a given assessment of hopelessness (i.e., baseline, 6, 24, and 48 months) reliably predicted attempted suicide up to 4 to 6 years later, but not beyond. Structural equation modeling indicated that hopelessness prospectively predicted attempted suicide even when controlling for previous attempts. Notably, a cut-point of 3 or greater on the Beck Hopelessness Scale yielded sensitivity and specificity values similar to those found in nonpsychotic populations using a cut-point of 9. Results suggest that hopelessness in individuals with psychotic disorders confers information about suicide risk above and beyond history of attempted suicide. Moreover, in comparison with nonpsychotic populations, even relatively modest levels of hopelessness appear to confer risk for suicide in psychotic disorders. PMID- 22320193 TI - Precipitating events in adolescent suicidal crises: exploring stress-reactive and nonreactive risk profiles. AB - Factors distinguishing adolescents who experienced a precipitating event in the week preceding a suicidal crisis from those who did not were examined. Among 130 suicidal inpatients (mean age = 15.01 years), those who experienced a precipitating event reported significantly lower depressive symptom scores, better perceived problem solving, less suicidal intent, and a lower rate of prior suicide attempts than those without a precipitating event. Levels of trait impulsivity, suicidal ideation, and current attempt status did not differentiate groups. Findings provide preliminary evidence consistent with at least two possible pathways to a suicidal crisis. Clinical implications and future directions are discussed. PMID- 22320194 TI - National suicide prevention lifeline: enhancing mental health care for suicidal individuals and other people in crisis. AB - Linking at-risk callers to ongoing mental health care is a key goal of crisis hotline interventions that has not often been addressed in evaluations of hotlines' effectiveness. We conducted telephone interviews with 376 suicidal and 278 nonsuicidal crisis callers to the National Suicide Prevention Lifeline (Lifeline) to assess rates of mental health care utilization following Lifeline calls and to assess attitudinal and structural barriers to service utilization. Postcall utilization rates were approximately 50% for suicidal and crisis callers who received mental health care referrals. Lack of health insurance and callers' perceptions about mental health problems emerged as significant barriers to accessing continued help. PMID- 22320195 TI - Can serum gamma-glutamyltransferase levels be useful at diagnosing gestational diabetes mellitus? AB - OBJECTIVE: The aim of this study was to evaluate plasma gamma-glutamyltransferase (GGT) in gestational diabetes mellitus (GDM) in pregnant women at oral glucose tolerance test (OGTT) and the diagnosis of GDM and to explore whether this activity is associated with metabolic parameters. METHOD: This prospective control study included 37 women with GDM and 42 women with normal glucose tolerance in pregnancy (control group). In the study group (GDM), blood was taken for analyzing 100 g OGTT from women who have abnormal 50 g glucose challenge test (GCT). RESULTS: Compared with the controls, the GDM group had significantly higher mean values for serum fasting glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), triglyceride and GGT. Within the GDM group, GGT levels were only negatively correlated with high-density lipoprotein (r = -0.41, p = 0.01). GGT was determined to be an independent metabolic parameter for GDM. While performing analyses receiver operational curve analysis, GGT cutoff set was set at 16 IU/L, the sensitivity was calculated as 86%, and specificity was as 37%. CONCLUSION: The increase at GGT level is an independent risk factor for GDM and identified as high-risk women for diagnosis of GDM. PMID- 22320196 TI - Interferon-inducible genes, TNF-related apoptosis-inducing ligand (TRAIL) and interferon inducible protein 27 (IFI27) are negatively regulated in leiomyomas: implications for a role of the interferon pathway in leiomyoma development. AB - Uterine leiomyomas are the most common tumors in the human female pelvis and the leading indication for pelvic surgery. Lack of understanding of the molecular pathogenesis of leiomyoma has put severe limitations on the availability of alternative treatments. Using an oligonucleotide micro-array-based hybridisation analysis we observed a group of genes with a broad range of functional activity differentially expressed in smooth muscle cells (SMC) derived from leiomyomas when compared to matched myometrial cells. Among them, two IFNalpha inducible genes, TRAIL and IFI27, were underexpressed in leiomyoma vs. myometrial cells. Expression levels of TRAIL and IFI27 were also measured in myometrial and leiomyoma cells by real-time quantitative PCR in basal condition and after IFNalpha stimulation. In both cell types, the transcription of the two genes resulted induced by IFNalpha but the IFI27 transcription stimulation was weaker in leiomyoma than myometrial cells whereas the TRAIL transcription stimulation resulted stronger in leiomyoma respect myometrial cells. Based on this finding and on previous observations we have hypothesized that a reduced response to IFNalpha stimulation might be involved in leiomyoma formation and growth. PMID- 22320198 TI - A general approach to synthesize asymmetric hybrid nanoparticles by interfacial reactions. AB - Asymmetric multicomponent nanoparticles (AMNPs) offer new opportunities for new generation materials with improved or new synergetic properties not found in their individual components. There is, however, an urgent need for a synthetic strategy capable of preparing hybrid AMNPs with fine-tuned structural and compositional complexities. Herein, we report a new paradigm for the controllable synthesis of polymer/metal AMNPs with well-controlled size, shape, composition, and morphology by utilizing interfacial polymerization. The hybrid AMNPs display a new level of structural-architectural sophistication, such as controlled domain size and the number of each component of AMNPs. The approach is simple, versatile, cost-effective, and scalable for synthesizing large quantities of AMNPs. Our method may pave a new route to the design and synthesis of advanced breeds of building blocks for functional materials and devices. PMID- 22320199 TI - Trends in the prevalence of invasive fungal infections from an analysis of annual records of autopsy cases of Toho University. AB - Clinical diagnosis of invasive fungal infections (IFIs) is sometimes difficult, and obtaining an accurate assessment of trends concerning the prevalence of IFIs is a challenge. The aim of this study was to determine trends in the prevalence of IFIs from an autopsy survey. The retrospective review of autopsy records stored in Toho University was performed on all documented cases with fungal infection from 1955 to 2006. A total of 411 cases of IFIs were detected among 10 297 autopsies. The prevalence of candidiasis decreased from 3.6% (1981-93) to 2.0% (1994-2006), and that of aspergillosis increased throughout the 52-year period and reached 2.0% (1994-2006). The prevalence of IFIs in the patient group comprising haematological disorders was significantly higher (19.9%) than in other patient groups (2.9%), of which the odds ratio was 18.4 for mucormycosis and 10.0 for aspergillosis. The lung was the most common organ involved irrespective of major fungal species, and most cases with candidiasis showed multiple-organ infection. Results confirmed the increasing prevalence of aspergillosis and high risk of IFIs in the patient group with haematological disorders. IFIs were also detected in an immunocompromised state caused not only by primary disease but also by treatment with anti-tumour drugs and corticosteroids. PMID- 22320200 TI - Development of a paper-based analytical device for colorimetric detection of select foodborne pathogens. AB - Foodborne pathogens are a major public health threat and financial burden for the food industry, individuals, and society, with an estimated 76 million cases of food-related illness occurring in the United States alone each year. Three of the most important causative bacterial agents of foodborne diseases are pathogenic strains of Escherichia coli , Salmonella spp., and Listeria monocytogenes , due to the severity and frequency of illness and disproportionally high number of fatalities. Their continued persistence in food has dictated the ongoing need for faster, simpler, and less expensive analytical systems capable of live pathogen detection in complex samples. Culture techniques for detection and identification of foodborne pathogens require 5-7 days to complete. Major improvements to molecular detection techniques have been introduced recently, including polymerase chain reaction (PCR). These methods can be tedious; require complex, expensive instrumentation; necessitate highly trained personnel; and are not easily amenable to routine screening. Here, a paper-based analytical device (MUPAD) has been developed for the detection of E. coli O157:H7, Salmonella Typhimurium, and L. monocytogenes in food samples as a screening system. In this work, a paper-based microspot assay was created by use of wax printing on filter paper. Detection is achieved by measuring the color change when an enzyme associated with the pathogen of interest reacts with a chromogenic substrate. When combined with enrichment procedures, the method allows for an enrichment time of 12 h or less and is capable of detecting bacteria in concentrations in inoculated ready-to-eat (RTE) meat as low as 10(1) colony-forming units/cm(2). PMID- 22320201 TI - Cooperation between catalytic and DNA binding domains enhances thermostability and supports DNA synthesis at higher temperatures by thermostable DNA polymerases. AB - We have previously introduced a general kinetic approach for comparative study of processivity, thermostability, and resistance to inhibitors of DNA polymerases [Pavlov, A. R., et al. (2002) Proc. Natl. Acad. Sci. U.S.A.99, 13510-13515]. The proposed method was successfully applied to characterize hybrid DNA polymerases created by fusing catalytic DNA polymerase domains with various sequence nonspecific DNA binding domains. Here we use the developed kinetic analysis to assess basic parameters of DNA elongation by DNA polymerases and to further study the interdomain interactions in both previously constructed and new chimeric DNA polymerases. We show that connecting helix-hairpin-helix (HhH) domains to catalytic polymerase domains can increase thermostability, not only of DNA polymerases from extremely thermophilic species but also of the enzyme from a faculatative thermophilic bacterium Bacillus stearothermophilus. We also demonstrate that addition of Topo V HhH domains extends efficient DNA synthesis by chimerical polymerases up to 105 degrees C by maintaining processivity of DNA synthesis at high temperatures. We found that reversible high-temperature structural transitions in DNA polymerases decrease the rates of binding of these enzymes to the templates. Furthermore, activation energies and pre-exponential factors of the Arrhenius equation suggest that the mechanism of electrostatic enhancement of diffusion-controlled association plays a minor role in binding of templates to DNA polymerases. PMID- 22320202 TI - The relation between urinary angiotensinogen and proteinuria in renal AA amyloidosis patients. AB - OBJECTIVE: The aim of this study was to evaluate the relationship of local intrarenal renin angiotensin system (RAS) with proteinuria in patients with renal AA amyloidosis. METHODS: Thirty-two patients with renal AA amyloidosis (19 male, mean age: 45 +/- 13 years) and sixteen healthy controls (5 male, mean age: 32 +/- 5 years) were included in this study. Spot urine samples were obtained to measure urinary angiotensinogen (AGT) using human AGT-ELISA, urinary creatinine and protein levels. Logarithmic transformations of urinary AGT-creatinine ratio log(UAGT/Ucre) and urinary protein-to-creatinine ratio (UPCR) were done to obtain the normal distributions of these parameters. RESULTS: Log(UAGT/UCre) was significantly higher in patients compared with the controls (1.88 +/- 0.92 ug/g vs. 1.25 +/- 0.70 ug/g; p = 0.023). Importantly a significantly positive correlation was found between log(UAGT/Ucre) and logUPCR in patients (r = 0.595, p = 0.006). CONCLUSIONS: Urinary AGT levels are higher in renal AA amyloidosis patients than in controls. Also, there is a significant positive correlation between urinary AGT and proteinuria in renal AA amyloidosis. PMID- 22320203 TI - The impacts of nature experience on human cognitive function and mental health. AB - Scholars spanning a variety of disciplines have studied the ways in which contact with natural environments may impact human well-being. We review the effects of such nature experience on human cognitive function and mental health, synthesizing work from environmental psychology, urban planning, the medical literature, and landscape aesthetics. We provide an overview of the prevailing explanatory theories of these effects, the ways in which exposure to nature has been considered, and the role that individuals' preferences for nature may play in the impact of the environment on psychological functioning. Drawing from the highly productive but disparate programs of research in this area, we conclude by proposing a system of categorization for different types of nature experience. We also outline key questions for future work, including further inquiry into which elements of the natural environment may have impacts on cognitive function and mental health; what the most effective type, duration, and frequency of contact may be; and what the possible neural mechanisms are that could be responsible for the documented effects. PMID- 22320204 TI - DNA-linker-induced surface assembly of ultra dense parallel single walled carbon nanotube arrays. AB - Ultrathin film preparations of single-walled carbon nanotube (SWNT) allow economical utilization of nanotube properties in electronics applications. Recent advances have enabled production of micrometer scale SWNT transistors and sensors but scaling these devices down to the nanoscale, and improving the coupling of SWNTs to other nanoscale components, may require techniques that can generate a greater degree of nanoscale geometric order than has thus far been achieved. Here, we introduce linker-induced surface assembly, a new technique that uses small structured DNA linkers to assemble solution dispersed nanotubes into parallel arrays on charged surfaces. Parts of our linkers act as spacers to precisely control the internanotube separation distance down to <3 nm and can serve as scaffolds to position components such as proteins between adjacent parallel nanotubes. The resulting arrays can then be stamped onto other substrates. Our results demonstrate a new paradigm for the self-assembly of anisotropic colloidal nanomaterials into ordered structures and provide a potentially simple, low cost, and scalable route for preparation of exquisitely structured parallel SWNT films with applications in high-performance nanoscale switches, sensors, and meta-materials. PMID- 22320206 TI - Studies of the ligand effect on the synthesis of dialuminoxanes by various beta diketiminato ligands. AB - Reactions of LH (L = HC[C(Me)N(2,6-Me(2)C(6)H(3))](2)) with Me(n)AlCl(3-n) in diethyl ether afforded the adducts LH.AlMe(n)(Cl)(3-n) (n = 2, 3; 1, 4; 0, 5) in good yields. Treatment of 3 at elevated temperatures in toluene resulted in LAlMeCl (2) by intramolecular elimination of methane. The controlled hydrolysis of LAlMeCl (2) with equimolar amounts of water in the presence of N-heterocyclic carbene (NHC) gave a mixture of [LAl(Me)](2)(MU-O) (7) and dimeric [LAlMe(MU OH)](2) (8). A convenient route for the preparation of [LAlMe(MU-OH)](2) (8) was the NHC-assisted controlled hydrolysis of LAlMeI (9). Stepwise hydrolysis of LAlH(2) (11) gave dialuminoxane hydride [LAl(H)](2)(MU-O) (12) and dialuminoxane hydroxide [LAl(OH)](2)(MU-O) (13), respectively. Anhydrous treatment of LAlCl(2) (1) or LAlMeCl (2) with Ag(2)O afforded chlorinated dialuminoxane [LAl(Cl)](2)(MU O) (14) and [LAl(Me)](2)(MU-O) (7), respectively. PMID- 22320207 TI - A Five-Factor Model framework for understanding childhood personality disorder antecedents. AB - The present contribution reviews evidence that supports the relevance of childhood antecedents of personality disorders, and advocates that the validity of a Five-Factor Model framework for describing general trait differences in childhood can be extended towards the field of developmental personality difficulties. In addition, we suggest that several traditional childhood Axis I conditions include a substantial trait component that may be responsible for the recurring finding that childhood Axis I disorders are predictive for adult Axis II disorders. Given the valuable information provided by a trait assessment, we further propose to integrate dimensional personality and personality pathology measures as standard tools in mental health assessments at a young age. PMID- 22320208 TI - Reconstruction of cranial defects with individually formed cranial prostheses made of polypropylene polyester knitwear: an analysis of 48 consecutive patients. AB - This article presents a new method of cranioplasty in which polypropylene polyester knitwear was used as the filling material. The basis for prosthesis shaping was a three-dimensional model of the defect made according to the patient's CT scans. Previously, such material has never been a subject of computer-aided design and computer-aided manufacturing (CAD/CAM) individual forming. The process of the prosthesis design included CT bone scans and mold preparation for each patient. Such prostheses were implanted in 48 patients with cranial defects. The total number of prostheses applied was 51. The follow-up time was at least 6 months up to 36 months. The group of treated patients is described here, and sample pictures are shown to illustrate the results. The smallest defect had a size of 15 cm(2); the biggest, 178 cm(2). The coverage and the aesthetic results were very good in all cases. Two patients had postoperative complications. The cranioplastic solution described here is a valuable addition to the existing reconstructive methods, because of the low cost of the implant, the ease of its adjustment to the shape of the defect, and the short time of preparation. PMID- 22320209 TI - Acetaminophen and acetylcysteine dose and duration: past, present and future. AB - Acetylcysteine has been utilized successfully in the treatment of acetaminophen overdose since the 1970s. Although prospective trials as to efficacy and safety of acetylcysteine were conducted, there were no randomized controlled trials. This commentary addresses the reasons for this, and the background to choice of dose of acetylcysteine utilized in the oral and IV dosing regimens. Nomograms to predict possible hepatotoxicity based upon time of ingestion of acetaminophen were developed from a relatively arbitrary definition of toxicity as an aspartate aminotransferase/alanine aminotransferase (ALT/AST) greater than 1000 IU/L. While these have proved generally useful, patients still continue to develop hepatic damage after acetaminophen overdose, particularly if they present late after ingestion. The optimum management of these patients remains unclear, and one area of uncertainty is the dose and duration of acetylcysteine in various circumstances. This article discusses the issues that need to be elucidated to better target changes in acetylcysteine dose. The potential for measurements of other markers to improve treatment selection is the subject of further research. PMID- 22320210 TI - A healthy volunteer study to investigate trace element contamination of blood samples by stainless steel venepuncture needles. AB - CONTEXT: The trace elements cobalt (Co), chromium (Cr), manganese (Mn) and nickel (Ni) are normally present at low concentrations in blood. There has been a concern that stainless steel venepuncture needles typically used for collection of blood samples may contaminate these samples, leading to the masking of deficiency states or causing potential clinical confusion as to whether an individual has a "toxic" concentration. OBJECTIVE: To determine whether there is any difference between the concentrations of the trace elements obtained by different methods of blood sampling. METHODS: We took blood samples using a standard venepuncture needle, a "butterfly" winged infusion needle (three consecutive samples) and a plastic intravenous cannula (three consecutive samples) from 10 healthy volunteers. We measured the concentrations of Co, Cr, Mn and Ni in the samples using Inductively Coupled Plasma Mass Spectrometry, and used analysis of variance (ANOVA) to investigate if there was any difference between the methods of blood sampling. RESULTS: The mean +/- standard deviation blood metal concentrations were: Co 0.33 +/- 0.2 MUg/l, Cr 2.43 +/- 1.55 MUg/l, Mn 8.07 +/- 7.74 MUg/l and Ni 10.4 +/- 4.69 MUg/l. There was considerable variation between blood metal concentrations of individual subjects and a few sporadic high values. By ANOVA, there was no significant difference between the metal concentrations measured using different methods of blood collection. CONCLUSIONS: It is not necessary to routinely use a plastic cannula for blood sampling for trace element analysis. However, it is possible that sporadic contamination due to stainless steel needles may occur, so we would recommend that unexpected high concentrations are verified by taking a second sample taken through a plastic cannula. PMID- 22320211 TI - Emergency department visits due to pesticide poisoning in South Korea, 2006-2009. AB - OBJECTIVES: The objective of this study is to estimate the numbers and rate of emergency department visits in South Korea that are the result of pesticide poisoning and to describe their epidemiologic characteristics. MATERIALS AND METHODS: Data collected from the National Emergency Department Information System were used to estimate the number of emergency department visits due to pesticide poisoning in South Korea for the period spanning 2006 through 2009. Emergency department visits for pesticide poisoning were defined by ICD-10 codes (T60.0 T60.9). National estimates and their 95% confidence intervals were calculated per 100 000 population. RESULTS: Among the 65 877 total poisoning-related emergency department visits in the data, 11 985 (18.2%) were emergency department visits resulting from pesticide poisoning. During the study period, the annual average rate of emergency department visits for pesticide poisoning was 26.8 per 100 000 population. Intentional pesticide poisoning (51.4%) was more frequent than unintentional. The fatality rate from intentional pesticide poisoning was also higher than that from unintentional or cases where the intention was unknown. In terms of age-specific rates of emergency department visits for pesticide poisoning, they increased with age, as did the gap between men and women. CONCLUSIONS: This study provide estimates for emergency department visits due to pesticide poisoning at the national level and suggests that pesticide poisonings, both intentional and unintentional, require significant public health interventions in South Korea. PMID- 22320212 TI - Subperitoneal pelvic exposure of elemental mercury from a broken thermometer. AB - Subperitoneal pelvic exposure of elemental mercury from a broken thermometer is quite rare. The outcome and intervention for such a situation is uncertain. A 10 month-old boy was exposed to elemental mercury when a mercury thermometer was broken while being used to measure a central temperature rectally. Deposits of mercury were localized in the subperitoneal pelvic cavity, as seen on consecutive abdominal films and CT scan. Serum and urine mercury concentrations were elevated but no systemic symptoms or signs were found. Laparoscopic surgery removed most of the mercury deposits but failed to remove them completely. At the 11-month follow-up, serum and urine mercury concentrations normalized and no systemic toxicity was present. PMID- 22320213 TI - Quality of life of parents diagnosed with cancer: change over time and influencing factors. AB - Suffering from cancer while having parental responsibilities can amplify the psychosocial strain that the disease puts on the individual as well as on the whole family system. Our longitudinal study examines changes in the quality of life of cancer patients in relation to parenthood. The quality of life of cancer patients is assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item version during the initial treatment period (T1) and compared to the quality of life 2 years later (T2). Two groups of patients are compared: those who have children below the age of 18 years (n= 41) and those who do not have children (n= 28). Shortly after being diagnosed with cancer (T1), both groups report a similarly low quality of life. Two years later (T2), individuals with children below the age of 18 report better quality of life on the majority of the dimensions assessed. However, variance analysis did not show that this is an independent effect of parenthood. In fact, having a partner and being female proved to impact the quality of life. These findings support the existing body of research on the influence of social support and gender on quality of life. The resulting limitations and suggestions on how to overcome them in further research are discussed. PMID- 22320214 TI - A Monte Carlo simulation study of methane clathrate hydrates confined in slit shaped pores. AB - Monte Carlo simulations are used to study the structure, stability, and dissociation mechanisms of methane hydrate crystals inside carbon-like slit shaped pores. The simulation conditions used mimic experimental studies of the dissociation of methane and propane hydrates in mesoporous silica gels (Handa, Y. P.; Stupin, D. J. Phys. Chem. 1992, 96, 8599). Simulations are performed under conditions of fixed methane pressure and fixed water loading, with the temperature increased in steps, with long equilibrations at each temperature. The initial structures of the confined hydrates are taken to be bulk-like, and pore widths chosen to accommodate integer or half-integer numbers of hydrate unit cells. Density profiles and orientational order parameter profiles are obtained and used to understand the structural changes associated with hydrate dissociation. Three different common water models, SPC/E, TIP4P, and TIP4P/2005, are used and the results compared. For water modeled using either the TIP4P or TIP4P/2005 potentials, dissociation temperatures are depressed proportionally to the inverse pore width, as predicted by the macroscopic Gibbs-Thomson equation. This behavior is observed for pores small enough that only half-cages of the clathrate structure are present. Experimental work has verified Gibbs-Thomson behavior for pores as small as 2 nm (Seshadri, K.; Wilder, J. W.; Smith, D. H. J. Phys. Chem. B 2001, 105, 2627); micropores of the size studied here have not yet been studied by experiment. Interestingly, the dissociation of hydrates modeled using the SPC/E water potential does not display the predicted pore-size dependence, and the dissociation mechanisms in this model seem to be quite different than those in the TIP4P-type models. In the SPC/E hydrates, with increasing temperature, cage dissocation occurs before methane desorption. In TIP4P-type hydrates, these processes occur either at the same temperature (to within the resolution of this study) or with dissociation occurring at higher temperatures than desorption. These simulations show that a variety of interesting clathrate structures and phase behaviors may be accessed in suitably designed microporous materials, with potentially useful applications in gas storage or separations. PMID- 22320215 TI - Single origin of human commensalism in the house sparrow. AB - The current, virtually worldwide distribution of the house sparrow (Passer domesticus) is a result of its commensal relationship with humans. It has been suggested that long before the advent of agriculture, an early glacial advance resulted in two disjunct ranges of ancestral house sparrows - one in the Middle East and another on the Indian subcontinent. Differentiation during this period of isolation resulted in two major groups of subspecies: the domesticus group and the indicus group. According to this hypothesis, commensalism with humans would have evolved independently in the two regions and at least twice. An alternative hypothesis is that morphological differences between the subspecies represent very recent differentiation, following expansions from a single source. To test between these hypotheses, we analysed genetic variation at the mitochondrial DNA control region and at three nuclear loci from several house sparrow populations in Europe, Asia and North Africa. No differentiation between the indicus and domesticus groups was found, supporting the single origin hypothesis. One of the subspecies in the indicus group, P. d. bactrianus, differs ecologically from other house sparrows in being migratory and in preferentially breeding in natural habitat. We suggest that bactrianus represents a relict population of the ancestral, noncommensal house sparrow. When agricultural societies developed in the Middle East about 10 000 years ago, a local house sparrow population of the bactrianus type adapted to the novel environment and eventually became a sedentary, human commensal. As agriculture and human civilizations expanded, house sparrows experienced a correlated and massive expansion in range and numbers. The pattern of genetic variation analysed here is consistent with this scenario. PMID- 22320216 TI - Polyelectrolyte mediated interactions in colloidal dispersions: hierarchical screening, simulations, and a new classical density functional theory. AB - The pair interaction between two charged colloidal particles, in the presence of a polyelectrolyte as well as simple salt, is analyzed theoretically. Of particular interest is the way in which such a combination of salts can be used to induce a strong, long-range attraction, with at most a minor free energy barrier. We show that the nature of the simple salt is highly relevant, i.e., 2:1, 1:1, and 1:2 salts generate quite different particle interaction free energies at the same overall ionic strength. We adopt several different theoretical levels of description. Defining simulations at the primitive model level with explicit simple salt as our reference, we invoke stepwise coarse graining with careful evaluations of each approximation. Representing monovalent simple ions by the ionic screening they generate is one such simplification. In order to proceed further, with additional computational savings, we also develop a correlation-corrected classical density functional theory. We analyze the performance of this theory with explicit spherical particles as well as in a flat surface geometry, utilizing Derjaguin's approximation. The calculations are particularly fast in the latter case, facilitating computational savings of many (typically 5-7) orders of magnitude, compared to corresponding simulations with explicit salt. Yet, the predictions are remarkably accurate, and considering the crudeness of the model itself, the density functional theory is a very attractive alternative to simulations. PMID- 22320217 TI - miR-30c-1* promotes natural killer cell cytotoxicity against human hepatoma cells by targeting the transcription factor HMBOX1. AB - Natural killer (NK) cells play a critical role in antitumor immunity, and the activation of NK cells is regulated by a series of NK cell receptors. Here, we show that crosslinking CD226, an important NK cell receptor, with the anti-CD226 mAb LeoA1 on NKL cells, regulated the expression of several microRNA and transmembrane tumor necrosis factor-alpha. Among them, miR-30c-1(*) was noticed because overexpression of miR-30c-1(*) triggered upregulation of transmembrane tumor necrosis factor-alpha expression and enhanced NK cell cytotoxicity against hepatoma cell lines SMMC-7721 and HepG2. Furthermore, we proved that the inhibitory transcription factor HMBOX1, which depressed the activation of NK cells, was the direct target gene of miR-30c-1(*). In conclusion, our results revealed a novel regulatory mechanism: miR-30c-1(*) promoted NK cell cytotoxicity against hepatoma cells by targeting HMBOX1. PMID- 22320218 TI - Estimating Brownian motion dispersal rate, longevity and population density from spatially explicit mark-recapture data on tropical butterflies. AB - 1. We develop a Bayesian method for analysing mark-recapture data in continuous habitat using a model in which individuals movement paths are Brownian motions, life spans are exponentially distributed and capture events occur at given instants in time if individuals are within a certain attractive distance of the traps. 2. The joint posterior distribution of the dispersal rate, longevity, trap attraction distances and a number of latent variables representing the unobserved movement paths and time of death of all individuals is computed using Gibbs sampling. 3. An estimate of absolute local population density is obtained simply by dividing the Poisson counts of individuals captured at given points in time by the estimated total attraction area of all traps. Our approach for estimating population density in continuous habitat avoids the need to define an arbitrary effective trapping area that characterized previous mark-recapture methods in continuous habitat. 4. We applied our method to estimate spatial demography parameters in nine species of neotropical butterflies. Path analysis of interspecific variation in demographic parameters and mean wing length revealed a simple network of strong causation. Larger wing length increases dispersal rate, which in turn increases trap attraction distance. However, higher dispersal rate also decreases longevity, thus explaining the surprising observation of a negative correlation between wing length and longevity. PMID- 22320219 TI - Response and survival of patients with chronic graft-versus-host disease treated by extracorporeal photochemotherapy: a retrospective study according to classical and National Institutes of Health classifications. AB - BACKGROUND: Chronic graft-versus-host disease (cGVHD) classification has recently been improved by the National Institutes of Health (NIH); patients' stratification with those new criteria has implications for patients' prognosis. STUDY DESIGN AND METHODS: To assess whether the NIH consensus classification (NCC) better predicts survival and response to extracorporeal photochemotherapy (ECP), and to identify variables associated with response and survival, we retrospectively analyzed 102 patients with cGVHD reclassified according to NCC treated with ECP (1997-2010) at our center. Cox regression was used in univariate and multivariate models. RESULTS: Of the 102 patients, 64 (62.7%) had classic cGVHD, 24 (23.5%) had overlap cGVHD, and seven (6.9%) patients each had late and persistent acute GVHD. The cumulative ECP-specific follow-up was 2333.3 person years. Response was complete in 16 (15.7%), partial in 38 (37.3%), minimal in 28 (27.5%), and absent in 20 (19.6%). Of the 22 deaths, 15 (68.2%) occurred among patients with minimal or no response (p = 0.031). The only variables associated with response were nonmyeloablative transplant (hazard ratio, 3.5; 95% confidence interval [CI], 1.36-9.08; p = 0.009), donor lymphocyte infusion (hazard ratio, 2.58; 95% CI, 1.2-5.56; p = 0.015), and lung involvement (hazard ratio, 0.34; 95% CI, 0.12-0.94; p = 0.038). CONCLUSION: ECP is a safe and effective treatment for cGVHD and response to ECP is the only variable that influences survival. We found no correlation between response and NCC clinical subtype, number, or degree of organ involvement, except for lung, or the variables mentioned above. Prospective studies are needed to identify subsets of patients with higher probability of response. PMID- 22320220 TI - Optimised radiological diagnosis of hepatic fungal infection during the treatment of leukemia. AB - Hepatic fungal infection is a frequent complication in patients receiving intensive chemotherapy for acute leukaemia. Hepatic lesions may be detected using computerised tomographic (CT) scans, but there is no standardised CT protocol for the diagnosis and follow-up of hepatic fungal infection. We therefore retrospectively analysed the number and the volume of hepatic fungal lesions in 24 CT of 20 consecutive patients treated for acute leukaemia during late-arterial and porto-venous phase. The mean number of lesions per patient was 31 (range: 3 105) in the late-arterial and 26 (3-81) in the porto-venous CT (P = 0.026). The mean total volume of all lesions was 6.45 ml in the late-arterial and 4.07 ml in the porto-venous CT representing a 1.6fold difference between the two CT scans (P = 0.008). The total volume of the lesions negatively correlated to the absolute contrast difference between liver parenchyma and liver vein (Pearson correlation, r = -0.62; P = 0.002). In conclusion, the late-arterial CT provides a superior distinction of hepatic lesions due to a delayed perfusion of the outer rim of the fungal lesions resulting in an extended visibility. The late-arterial CT is superior to the porto-venous CT for initial diagnosis and follow-up of hepatic fungal infection. PMID- 22320221 TI - Hum interrupted: life, death, and afterward. PMID- 22320222 TI - A Ca2+-dependent chloride current and Ca2+ influx via Ca(v)1.2 ion channels play major roles in P2Y receptor-mediated pulmonary vasoconstriction. AB - BACKGROUND AND PURPOSE: ATP, UTP and UDP act at smooth muscle P2X and P2Y receptors to constrict rat intrapulmonary arteries, but the underlying signalling pathways are poorly understood. Here, we determined the roles of the Ca2+ dependent chloride ion current (I(Cl,Ca)), Ca(v)1.2 ion channels and Ca2+ influx. EXPERIMENTAL APPROACH: Isometric tension was recorded from endothelium-denuded rat intrapulmonary artery rings (i.d. 200-500 um) mounted on a wire myograph. KEY RESULTS: The I(Cl,Ca) blockers, niflumic acid and 4,4'-diisothiocyanatostilbene 2,2'-disulfonic acid and the Ca(v)1.2 channel blocker, nifedipine, reduced peak amplitude of contractions evoked by UTP and UDP by ~45-50% and in a non-additive manner. Ca2+-free buffer inhibited responses by ~70%. Niflumic acid and nifedipine similarly depressed contractions to ATP, but Ca2+-free buffer almost abolished the response. After peaking, contractions to UTP and UDP decayed slowly by 50-70% to a sustained plateau, which was rapidly inhibited by niflumic acid and nifedipine. Contractions to ATP, however, reversed rapidly and fully. Tannic acid contracted tissues per se and potentiated nucleotide-evoked contractions. CONCLUSIONS AND IMPLICATIONS: I (Cl,Ca) and Ca2+ influx via Ca(v)1.2 ion channels contribute substantially and equally to contractions of rat intrapulmonary arteries evoked by UTP and UDP, via P2Y receptors. ATP also activates these mechanisms via P2Y receptors, but the greater dependence on extracellular Ca2+ most likely reflects additional influx through the P2X1 receptor pore. The lack of a sustained response to ATP is probably due to it acting at P2 receptor subtypes that desensitize rapidly. Thus multiple signalling mechanisms contribute to pulmonary artery vasoconstriction mediated by P2 receptors. PMID- 22320223 TI - Novel magnetic Fe3O4@CdSe composite quantum dot-based electrochemiluminescence detection of thrombin by a multiple DNA cycle amplification strategy. AB - A novel small magnetic electrochemiluminescent Fe(3)O(4)@CdSe composite quantum dot (QD) was facilely prepared and successfully applied to sensitive electrochemiluminescence (ECL) detection of thrombin by a multiple DNA cycle amplification strategy for the first time. The as-prepared composite QDs feature intense ECL, excellent magnetism, strong fluorescence, and favorable biocompatibility, which offers promising advantages for ECL biosensing. ECL of the composite QDs was efficiently quenched by gold nanoparticles (NPs). Taking advantages of the unique and attractive ECL and magnetic characteristics of the composite QDs, a novel DNA-amplified detection method based on ECL quenching was thus developed for a sensitive assay of thrombin. More importantly, the DNA devices by cleavage reaction were cycled multiple rounds, which greatly amplified the ECL signal and much improve the detection sensitivity. This flexible biosensing system exhibits not only high sensitivity and specificity but also excellent performance in real human serum assay. The present work opens a promising approach to develop magnetic quantum dot-based amplified ECL bioassays, which has wider potential application with more favorable analytical performances than other ECL reagent-based systems. Moreover, the composite QDs are suitable for long-term fluorescent cellular imaging, which also highlights the promising directions for further development of QD-based in vitro and in vivo imaging materials. PMID- 22320224 TI - Pulmonary hypertension before first and second lung transplantation. AB - BACKGROUND: Pulmonary hypertension (PH) is frequently encountered in patients with advanced lung disease before the first and second lung transplantation. We sought to determine whether there is any relationship between pulmonary hemodynamics obtained before first and second lung transplantation. We also assessed whether PH has prognostic implications in lung transplant patients going for second transplantation. METHODS: We included consecutive adult (16-yr-old or older) patients who underwent lung re-transplantation, between 1997 and 2009, and had right heart catheterization before their first and second lung transplantation. RESULTS: Eighteen patients were included in the study. Age at first transplantation was 50.4 (SD 10.4) yr, and bronchiolitis obliterans syndrome (BOS) in the transplanted lung was the only indication for re transplantation. PH was observed in 39% of the patients before the first lung transplant and in 56% of the subjects before re-transplantation (p = 0.91). Pre capillary PH was present in 28% (n = 5) and 33% (n = 6) of the patients before first and second lung transplantation, respectively. None of the hemodynamic variables obtained before the first transplant predicted the development of PH before re-transplantation. PH before re-transplantation did not predict survival or development of BOS after re-transplantation. CONCLUSIONS: PH before initial lung transplantation did not predict the development of PH before the second transplantation. In our cohort, PH before second lung transplantation did not predict outcomes after re-transplantation. PMID- 22320225 TI - Structural and functional characterization of the product of disease-related factor H gene conversion. AB - Numerous complement factor H (FH) mutations predispose patients to atypical hemolytic uremic syndrome (aHUS) and other disorders arising from inadequately regulated complement activation. No unifying structural or mechanistic consequences have been ascribed to these mutants beyond impaired self-cell protection. The S1191L and V1197A mutations toward the C-terminus of FH, which occur in patients singly or together, arose from gene conversion between CFH encoding FH and CFHR1 encoding FH-related 1. We show that neither single nor double mutations structurally perturbed recombinant proteins consisting of the FH C-terminal modules, 19 and 20 (FH19-20), although all three FH19-20 mutants were poor, compared to wild-type FH19-20, at promoting hemolysis of C3b-coated erythrocytes through competition with full-length FH. Indeed, our new crystal structure of the S1191L mutant of FH19-20 complexed with an activation-specific complement fragment, C3d, was nearly identical to that of the wild-type FH19 20:C3d complex, consistent with mutants binding to C3b with wild-type-like affinity. The S1191L mutation enhanced thermal stability of module 20, whereas the V1197A mutation dramatically decreased it. Thus, although mutant proteins were folded at 37 degrees C, they differ in conformational rigidity. Neither single substitutions nor double substitutions increased measurably the extent of FH19-20 self-association, nor did these mutations significantly affect the affinity of FH19-20 for three glycosaminoglycans, despite critical roles of module 20 in recognizing polyanionic self-surface markers. Unexpectedly, FH19-20 mutants containing Leu1191 self-associated on a heparin-coated surface to a higher degree than on surfaces coated with dermatan or chondroitin sulfates. Thus, potentially disease-related functional distinctions between mutants, and between FH and FH-related 1, may manifest in the presence of specific glycosaminoglycans. PMID- 22320226 TI - Acute-phase serum amyloid A: perspectives on its physiological and pathological roles. AB - Serum amyloid A (SAA), a protein originally of interest primarily to investigators focusing on AA amyloidogenesis, has become a subject of interest to a very broad research community. SAA is still a major amyloid research topic because AA amyloid, for which SAA is the precursor, is the prototypic model of in vivo amyloidogenesis and much that has been learned with this model has been applicable to much more common clinical types of amyloid. However, SAA has also become a subject of considerable interest to those studying (i) the synthesis and regulation of acute phase proteins, of which SAA is a prime example, (ii) the role that SAA plays in tissue injury and inflammation, a situation in which the plasma concentration of SAA may increase a 1000-fold, (iii) the influence that SAA has on HDL structure and function, because during inflammation the majority of SAA is an apolipoprotein of HDL, (iv) the influence that SAA may have on HDL's role in reverse cholesterol transport, and therefore, (v) SAA's potential role in atherogenesis. However, no physiological role for SAA, among many proposed, has been widely accepted. None the less from an evolutionary perspective SAA must have a critical physiological function conferring survival-value because SAA genes have existed for at least 500 million years and SAA's amino acid sequence has been substantially conserved. An examination of the published literature over the last 40 years reveals a great deal of conflicting data and interpretation. Using SAA's conserved amino acid sequence and the physiological effects it has while in its native structure, namely an HDL apolipoprotein, we argue that much of the confounding data and interpretation relates to experimental pitfalls not appreciated when working with SAA, a failure to appreciate the value of physiologic studies done in the 1970-1990 and a current major focus on putative roles of SAA in atherogenesis and chronic disease. When viewed from an evolutionary perspective, published data suggest that acute-phase SAA is part of a systemic response to injury to recycle and reuse cholesterol from destroyed and damaged cells. This is accomplished through SAA's targeted delivery of HDL to macrophages, and its suppression of ACAT, the enhancement of neutral cholesterol esterase and ABC transporters in macrophages. The recycling of cholesterol during serious injury, when dietary intake is restricted and there is an immediate and critical requirement of cholesterol in the generation of myriads of cells involved in inflammation and repair responses, is likely SAA's important survival role. Data implicating SAA in atherogenesis are not relevant to its evolutionary role. Furthermore, in apoE(-/-) mice, domains near the N- and C- termini of SAA inhibit the initiation and progression of aortic lipid lesions illustrating the conflicting nature of these two sets of data. PMID- 22320227 TI - GSTP1 expression predicts poor pathological complete response to neoadjuvant chemotherapy in ER-negative breast cancer. AB - The purpose of the present study was to investigate the association of glutathione S-transferase P1 (GSTP1) expression with resistance to neoadjuvant paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (P-FEC) in human breast cancers. The relationship of GSTP1 expression and GSTP1 promoter hypermethylation with intrinsic subtypes was also investigated. In this study, primary breast cancer patients (n = 123, stage II-III) treated with neoadjuvant P FEC were analyzed. Tumor samples were obtained by vacuum-assisted core biopsy before P-FEC. GSTP1 expression was determined using immunohistochemistry, GSTP1 promoter methylation index (MI) using bisulfite methylation assay and intrinsic subtypes using DNA microarray. The pathological complete response (pCR) rate was significantly higher in GSTP1-negative tumors (80.0%) than GSTP1-positive tumors (30.6%) (P = 0.009) among estrogen receptor (ER)-negative tumors but not among ER positive tumors (P = 0.267). Multivariate analysis showed that GSTP1 was the only predictive factor for pCR (P = 0.013) among ER-negative tumors. Luminal A, luminal B and HER2-enriched tumors showed a significantly lower GSTP1 positivity than basal-like tumors (P = 0.002, P < 0.001 and P = 0.009, respectively), while luminal A, luminal B and HER2-enriched tumors showed a higher GSTP1 MI than basal like tumors (P = 0.076, P < 0.001 and P < 0.001, respectively). In conclusion, these results suggest the possibility that GSTP1 expression can predict pathological response to P-FEC in ER-negative tumors but not in ER-positive tumors. Additionally, GSTP1 promoter hypermethylation might be implicated more importantly in the pathogenesis of luminal A, luminal B and HER2-enriched tumors than basal-like tumors. PMID- 22320228 TI - Fe4 cluster and a buckled macrocycle complex from the reduction of [(dmgBF2)2Fe(L)2] (L = MeCN, (t)Bu(i)NC). AB - We report the syntheses, X-ray structures, and reductive electrochemistry of the Fe(II) complexes [(dmgBF(2))(2)Fe(MeCN)(2)] (1; dmg = dimethylglyoxime, MeCN = acetonitrile) and [(dmgBF(2))Fe((t)Bu(i)NC)(2)] (2; (t)Bu(i)NC = tert butylisocyanide). The reaction of 1 with Na/Hg amalgam led to isolation and the X ray structure of [(dmgBF(2))(2)Fe(glyIm)] (3; glyIm = glyimine), wherein the (dmgBF(2))(2) macrocyclic frame is bent to accommodate the binding of a bidentate apical ligand. We also report the X-ray structure of a rare mixed-valence Fe(4) cluster with supporting dmg-type ligands. In the structure of [(dmg(2)BF(2))(3)Fe(3)((1)/(2)dmg)(3)Fe(O)(6)] (4), the (dmgBF(2))(2) macrocycle has been cleaved, eliminating BF(2) groups. Density functional theory calculations and electron paramagnetic resonance data are in accordance with a central Fe(III) ion surrounded by three formally Fe(II)dmg(2)BF(2) units. PMID- 22320229 TI - Efficacy of clinical and radiological methods to identify second mesiobuccal canals in maxillary first molars. AB - INTRODUCTION: The success of endodontic treatment depends on the identification of all root canals. Technological advances have facilitated this process as well as the assessment of internal anatomical variations. The aim of this study was to compare the efficacy of clinical and radiological methods in locating second mesiobuccal canals (MB2) in maxillary first molars. METHODS: Fifty patients referred for analysis; access and clinical analysis; cone-beam endodontic treatment of their maxillary first molars were submitted to the following assessments: analysis; access and clinical analysis; cone-beam computed tomography (CBCT); post-CBCT clinical analysis; clinical analysis using an operating microscope; and clinical analysis after Start X ultrasonic inserts in teeth with negative results in all previous analyses. RESULTS: Periapical radiographic analysis revealed the presence of MB2 in four (8%) teeth, clinical analysis in 25 (50%), CBCT analysis in 27 (54%) and clinical analysis following CBCT and using an operating microscope in 27 (54%) and 29 (58%) teeth, respectively. The use of Start X ultrasonic inserts allowed one to detect two additional teeth with MB2 (62%). According to Vertucci's classification 48% of the mesiobuccal canals found were type I, 28% type II, 18% type IV and 6% type V. Statistical analysis showed no significant differences (p > 0.5) in the ability of CBCT to detect MB2 canals when compared with clinical assessment with or without an operating microscope. A significant difference (p < 0.001)was found only between periapical radiography and clinical/CBCT evaluations. CONCLUSION: Combined use of different methods increased the detection ofthe second canal in MB roots, but without statistical difference among CBCT, operating microscope, Start X and clinical analysis. PMID- 22320230 TI - Charged nanoparticle dynamics in water induced by scanning transmission electron microscopy. AB - Using scanning transmission electron microscopy we image ~4 nm platinum nanoparticles deposited on an insulating membrane, where the membrane is one of two electron-transparent windows separating an aqueous environment from the microscope's high vacuum. Upon receiving a relatively moderate dose of ~10(4) e/nm(2), initially immobile nanoparticles begin to move along trajectories that are directed radially outward from the center of the field of view. With larger dose rates the particle motion becomes increasingly dramatic. These observations demonstrate that, even under mild imaging conditions, the in situ electron microscopy of aqueous environments can produce electrophoretic charging effects that dominate the dynamics of nanoparticles under observation. PMID- 22320231 TI - The use of information theory in evolutionary biology. AB - Information is a key concept in evolutionary biology. Information stored in a biological organism's genome is used to generate the organism and to maintain and control it. Information is also that which evolves. When a population adapts to a local environment, information about this environment is fixed in a representative genome. However, when an environment changes, information can be lost. At the same time, information is processed by animal brains to survive in complex environments, and the capacity for information processing also evolves. Here, I review applications of information theory to the evolution of proteins and to the evolution of information processing in simulated agents that adapt to perform a complex task. PMID- 22320232 TI - Replication and infectivity of a novel genotype 1b hepatitis C virus clone. AB - Hepatitis C virus infection is a major public health problem because of an estimated 170 million carriers worldwide. Genotype 1b is the major subtype of HCV in many countries and is resistant to interferon therapy. Study of the viral life cycle is important for understanding the mechanisms of interferon resistance of genotype 1b HCV strains. For such studies, genotype 1b HCV strains that can replicate and produce infectious virus particles in cultured cells are required. In the present study, we isolated HCV cDNA, which we named the NC1 strain, from a patient with acute severe hepatitis. Subgenomic replicon experiments revealed that several mutations enhanced the colony-formation efficiency of the NC1 replicon. The full-length NC1 genome with these adaptive mutations could replicate in cultured cells and produce infectious virus particles. The density gradient profile and morphology of the secreted virus particles were similar to those reported for the JFH-1 virus. Further introduction of a combination of mutations of the NS3 and NS5a regions into the NC1 mutants further enhanced secreted core protein levels and infectious virus titers in the culture medium of HCV-RNA-transfected cells. However, the virus infection efficiency was not sufficient for autonomous virus propagation in cultured cells. In conclusion, we established a novel cell culture-adapted genotype 1b HCV strain, termed NC1, which can produce infectious virus when the viral RNA is transfected into cells. This system provides an important opportunity for studying the life cycle of the genotype 1b HCV. PMID- 22320233 TI - Factors affecting the turnaround time for manufacturing, testing, and release of cellular therapy products prepared at multiple sites in support of multicenter cardiovascular regenerative medicine protocols: a Cardiovascular Cell Therapy Research Network (CCTRN) study. AB - BACKGROUND: Cellular therapy studies are often conducted at multiple clinical sites to accrue larger patient numbers. In many cases this necessitates use of localized good manufacturing practices facilities to supply the cells. To assure consistent quality, oversight by a quality assurance group is advisable. In this study we report the findings of such a group established as part of the Cardiovascular Cell Therapy Research Network (CCTRN) studies involving use of autologous bone marrow mononuclear cells (ABMMCs) to treat myocardial infarction and heart failure. STUDY DESIGN AND METHODS: Factors affecting cell manufacturing time were studied in 269 patients enrolled on three CCTRN protocols using automated cell processing system (Sepax, Biosafe SA)-separated ABMMCs. The cells were prepared at five good manufacturing practices cell processing facilities and delivered to local treatment sites or more distant satellite centers. RESULTS: Although the Sepax procedure takes only 90 minutes, the total time for processing was approximately 7 hours. Contributing to this were incoming testing and device preparation, release testing, patient randomization, and product delivery. The mean out-of-body time (OBT), which was to be less than 12 hours, averaged 9 hours. A detailed analysis of practices at each center revealed a variety of factors that contributed to this OBT. CONCLUSION: We conclude that rapid cell enrichment procedures may give a false impression of the time actually required to prepare a cellular therapy product for release and administration. Institutional procedures also differ and can contribute to delays; however, in aggregate it is possible to achieve an overall manufacturing and testing time that is similar at multiple facilities. PMID- 22320234 TI - Synthesis of benzoylacetonitriles from Pd-catalyzed carbonylation of aryl iodides and trimethylsilylacetonitrile. AB - Palladium-catalyzed carbonylation of aryl iodides and trimethylsilylacetonitrile to produce benzoylacetonitrile derivatives through a one-pot, three-component reaction is described. This preparation method provides good yields of the carbonylated products without any additional ligands. It has a broad substrate scope with a high tolerance for a variety of functional groups. PMID- 22320235 TI - Cancer-associated orthotopic myofibroblasts stimulates the motility of gastric carcinoma cells. AB - Tumor progression has been recognized as the product of evolving crosstalk between cancer cells and the surrounding stromal cells. Cancer-associated orthotopic myofibroblasts may be linked to the progression of gastric carcinomas. To understand the significance of orthotopic myofibroblasts, we examined the effects of cancer-associated orthotopic myofibroblasts on the malignant phenotype of gastric cancer cells. Three human gastric cancer cell lines (OCUM-2MD3, OCUM 12, MKN-45) and four human gastric fibroblast cell lines (cancer-associated orthotopic fibroblast [CaF]-29, CaF-33, normal orthotopic fibroblast [NF]-29, NF 33) were used. The cancer-associated orthotopic fibroblast cell lines CaF-29 and CaF-33 were established from a tumoral gastric wall, and normal orthotopic fibroblast NF-29 and NF-33 were established from a non-tumoral gastric wall. Fibroblasts that were alpha-smooth muscle actin-positive were defined as myofibroblasts. We examined the effects of cancer-associated orthotopic myofibroblasts on the aggressiveness of gastric cancer cells by wound-healing assay, invasion assay, and RT-PCR. The ratios of myofibroblasts in CaF-29 (33%) and CaF-33 (46%) were significantly (P < 0.001) greater than those in NF-29 (11%) or NF-33 (13%). Although all four orthotopic fibroblast lines increased the motility of gastric cancer cells, including migration and invasion ability, the motility-stimulating activity of cancer-associated fibroblasts (CaF-29 and CaF 33) was significantly higher than that of normal fibroblasts (NF-29 and NF-33). These motility-stimulating activities of cancer-associated orthotopic fibroblasts were downregulated by Smad2 siRNA treatment and anti-transforming growth factor beta neutralizing antibody. These findings suggest that cancer-associated orthotopic myofibroblasts may play an important role in the progression of gastric cancers and that transforming growth factor-beta produced by myofibroblasts may be one of the factors associated with the aggressiveness of gastric carcinoma cells. PMID- 22320236 TI - Sequence-selective single-molecule alkylation with a pyrrole-imidazole polyamide visualized in a DNA nanoscaffold. AB - We demonstrate a novel strategy for visualizing sequence-selective alkylation of target double-stranded DNA (dsDNA) using a synthetic pyrrole-imidazole (PI) polyamide in a designed DNA origami scaffold. Doubly functionalized PI polyamide was designed by introduction of an alkylating agent 1-(chloromethyl)-5-hydroxy 1,2-dihydro-3H-benz[e]indole (seco-CBI) and biotin for sequence-selective alkylation at the target sequence and subsequent streptavidin labeling, respectively. Selective alkylation of the target site in the substrate DNA was observed by analysis using sequencing gel electrophoresis. For the single molecule observation of the alkylation by functionalized PI polyamide using atomic force microscopy (AFM), the target position in the dsDNA (~200 base pairs) was alkylated and then visualized by labeling with streptavidin. Newly designed DNA origami scaffold named "five-well DNA frame" carrying five different dsDNA sequences in its cavities was used for the detailed analysis of the sequence selectivity and alkylation. The 64-mer dsDNAs were introduced to five individual wells, in which target sequence AGTXCCA/TGGYACT (XY = AT, TA, GC, CG) was employed as fully matched (X = G) and one-base mismatched (X = A, T, C) sequences. The fully matched sequence was alkylated with 88% selectivity over other mismatched sequences. In addition, the PI polyamide failed to attach to the target sequence lacking the alkylation site after washing and streptavidin treatment. Therefore, the PI polyamide discriminated the one mismatched nucleotide at the single-molecule level, and alkylation anchored the PI polyamide to the target dsDNA. PMID- 22320237 TI - The impact of colorectal cancer and self-efficacy beliefs on work ability and employment status: a longitudinal study. AB - We examined how colorectal cancer patients' treatment and symptom management impacted perceptions of work ability and subsequent work decisions. Fifty patients completed questionnaires at baseline (post-surgery/pretreatment), 3 months and 6 months. Questionnaires assessed fatigue, depression, quality-of-life (QoL), cancer self-efficacy, job self-efficacy (JSE) and work ability. Factors related to perceived work ability were occupation (beta= 0.31, P= 0.0005) and QoL (beta= 0.42, P= 0.01) at baseline, treatment type (beta=-0.19, P= 0.05) at 3 months, and JSE at 3 months (beta= 0.57, P= 0.0005) and 6 months (beta= 0.50, P= 0.006). Factors related to being on sick leave were lower levels of JSE (OR = 2.20, 95% CI: 1.17-4.13) at baseline and being employed in a manual occupation (OR = 0.03, 95% CI: 0.00-0.86), and perceived work ability (OR = 3.05, 95% CI: 1.00-12.80) at 6 months. Along with self-assessed work ability at baseline (beta= 0.67, P= 0.0005), receiving chemotherapy or a combination of treatments (beta= 0.24, P= 0.05) were the strongest predictors of poorer perceptions of follow-up work ability. Self-efficacy beliefs may add to understanding and should be considered in future research. PMID- 22320238 TI - Double heterozygous mutations of MITF and PAX3 result in Waardenburg syndrome with increased penetrance in pigmentary defects. AB - Waardenburg syndrome (WS) is characterized by sensorineural hearing loss and pigmentary defects of the hair, skin, and iris. Heterozygous mutations of MITF and its transactivator gene PAX3 are associated with Waardenburg syndrome type II (WS2) and type I (WS1), respectively. Most patients with MITF or PAX3 mutations, however, show variable penetrance of WS-associated phenotypes even within families segregating the same mutation, possibly mediated by genetic background or specific modifiers. In this study, we reported a rare Waardenburg syndrome simplex family in which a pair of WS parents gave birth to a child with double heterozygous mutations of MITF and PAX3. Compared to his parents who carried a single mutation in either MITF or PAX3, this child showed increased penetrance of pigmentary defects including white forelock, white eyebrows and eyelashes, and patchy facial depigmentation. This observation suggested that the expression level of MITF is closely correlated to the penetrance of WS, and variants in transcription regulator genes of MITF may modify the relevant clinical phenotypes. PMID- 22320239 TI - Rorschach Comprehensive System (CS) reference data for Israeli adolescents. AB - This study presents Rorschach Comprehensive System (CS; Exner, 1974, 2003) data for a sample of 100 Israeli nonpatient adolescents divided into 2 age-based groups: 11-14 (n = 42) and 15-18 (n = 58). The data are compared to those derived from the international project of Meyer, Erdberg, and Shaffer (2007). The results suggest that contemporary Israeli adolescents demonstrate age-appropriate inclination to show excessive self-inspection (FD), to be overly individualistic, perceiving reality in a unique and unconventional manner (elevated Xu%; lowered X+% and P), and to be involved in scientific issues (elevated Sc). The age-based group of 11 to 14, however, also tends to show difficulties in affect modulation (C > 0). Nonetheless, Israeli nonpatient adolescents are quite unlikely and not more than nonpatient adults, to show elevation on the major CS constellations of psychopathological manifestations. Although these observations are mostly in agreement with data collected from their peers around the world, the Israeli youngsters seem to be more similar to adults than to youngsters from other countries as to various CS measures, including those pointing to openness and attentiveness to stimuli (i.e., Lambda, F%). The main conclusion is that with the exception of some age-appropriate deviations, the international reference data for adults can be used for evaluating psychopathology in adolescents. PMID- 22320240 TI - Nanouidic compaction of DNA by like-charged protein. AB - The effects of the like-charged proteins bovine serum albumin and hemoglobin on the conformation and compaction of single DNA molecules confined in rectangular nanochannels were investigated with fluorescence microscopy. The channels have lengths of 50 MUm and cross-sectional diameters in the range of 80-300 nm. In the wider channels, the DNA molecules are compressed and eventually condense into a compact form with increasing concentration of protein. In the narrow channels, no condensation was observed. The threshold concentration for condensation depends on the channel cross-sectional diameter as well as the ionic strength of the supporting medium. The critical values for full compaction are typically less than one-tenth of a millimolar. In the bulk phase and in the same environmental conditions, no condensation was observed. Anisotropic nanoconfinement hence facilitates compaction of DNA by negatively charged protein. We tentatively interpret this behavior in terms of enhanced depletion interaction between segments of the DNA molecule due to orientation order imposed by the channel walls. PMID- 22320241 TI - Early conversion to a sirolimus-based, calcineurin-inhibitor-free immunosuppression in the SMART trial: observational results at 24 and 36months after transplantation. AB - Early conversion to a calcineurin-inhibitor (CNI)-free maintenance immunosuppression with sirolimus (SRL), mycophenolate mofetil (MMF) and steroids was associated with an improved 1-year renal function as compared with a cyclosporine (CsA)-based regimen (SMART core-study). This observational follow-up describes 132 patients followed up within the SMART study framework for 36months. At 36months, renal function continued to be superior in SRL-treated patients [ITT eGFR(@36m) : 60.88 vs. 53.72 (CsA) ml/min/1.73m(2) , P=0.031]. However, significantly more patients discontinued therapy in the SRL group 59.4% vs.42.3% (CsA). Patient [99% (SRL) vs.97% (CsA) and graft 96% (SRL) vs.94% (CsA)] survival at 36months was excellent in both arms. There was no difference in late rejection episodes. Late infections and adverse events were similar in both arms except of a higher rate of hyperlipidemia in SRL and a higher incidence of malignancy in CsA-treated patients. In a multivariate analysis, donor age >60years, S creatinine at conversion >2mg/dl, CMV naive(-) recipients and immunosuppression with CsA were predictive of an impaired renal function at 36months. Early conversion to a CNI-free SRL-based immunosuppression is associated with a sustained improvement of renal function up to 36months after transplantation. Patient selection will be key to derive long-term benefit and avoid treatment failure using this mTOR-inhibitor-based immunosuppressive regimen. PMID- 22320242 TI - Plastic responses to parents and predators lead to divergent shoaling behaviour in sticklebacks. AB - Population divergence in antipredator defence and behaviour occurs rapidly and repeatedly. Genetic differences, phenotypic plasticity or parental effects may all contribute to divergence, but the relative importance of each of these mechanisms remains unknown. We exposed juveniles to parents and predators to measure how induced changes contribute to shoaling behaviour differences between two threespine stickleback species (benthics and limnetics: Gasterosteus spp). We found that limnetics increased shoaling in response to predator attacks, whereas benthics did not alter their behaviour. Care by limnetic fathers led to increased shoaling in both limnetic and benthic offspring. Shoaling helps limnetics avoid trout and avian predation; our results suggest that this adaptive behaviour is the result of a combination of paternal effects, predator-induced plasticity and genetic differences between species. These results suggest that plasticity substantially contributes to the rapid divergence in shoaling behaviour across the post-Pleistocene radiation of sticklebacks. PMID- 22320243 TI - Targeting G protein and phosphorylation dependent signalling molecules for anticancer therapy. PMID- 22320244 TI - An ROP screening dilemma: hereditary cataracts developing in a premature infant after birth. AB - A female infant born prematurely at 23 weeks' gestational age developed bilateral hereditary cataracts at post-menstrual age 33 weeks, which precluded retinopathy of prematurity screening. The infant underwent right cataract extraction 1 week later, and retinopathy of prematurity was monitored by examining the right eye. In the seventeenth week of life (post-menstrual age 40 weeks), the cataract was removed from the left eye. Visual outcome at 19 months of age was good in both eyes. Very early cataract extraction may be necessary in premature infants to allow ROP evaluations. PMID- 22320245 TI - Enamel properties after tooth bleaching with hydrogen/carbamide peroxides in association with a CPP-ACP paste. AB - BACKGROUND: This study evaluated the impact of bleaching teeth using blends of a CPP-ACP paste (MI Paste; MI) and carbamide/hydrogen peroxides in different proportions on surface properties of bleached enamel. METHODS: Ninety bovine incisors were bleached with 7.5% hydrogen peroxide (HP), 16% carbamide peroxide (CP), MI and blends of HP or CP:MI at three proportions (1:1, 2:1, 1:2). Hardness and roughness were measured at baseline and after bleaching. Enamel morphology was evaluated by Scanning Electron Microscopy (SEM). The data were analyzed by two-way ANOVA for repeated measurements and Tukey's test. RESULTS: Most of the samples bleached with MI in combination with peroxides presented increased hardness and roughness which were associated to mineral deposition, as observed by SEM images. Blends with higher fractions of MI did not offer superior benefits. CONCLUSIONS: The use of a CPP-ACP paste mixed to carbamide/hydrogen peroxides can decrease adverse side-effects from tooth bleaching on an enamel surface. PMID- 22320246 TI - Quality of life and stimulus perception in patients' rehabilitated with complete denture. AB - The objective of this study was to evaluate and correlate quality of life (QoL), and stimulus perception of complete denture users, before and after the insertion of new prostheses. We selected 60 patients using bimaxillary complete conventional dentures who needed to replace their prostheses. During anamnesis, we collected demographic data and applied the Oral Health Impact Profile for Edentulous Patients (OHIP-EDENT) questionnaire and stimulus perception questionnaire (PERCEPTION). Before installation of new prostheses, the patients responded to OHIP-EDENT questionnaire, and on the day of installation, they responded to PERCEPTION questionnaire. At the patients' 3-month follow-up, we re administered the OHIP-EDENT and PERCEPTION questionnaires. The Wilcoxon and MacNemar tests were used to compare patient responses between the time points analysed. Most of the OHIP-EDENT items showed a highly significant impact of the new prostheses on oral health (P <= 0.003). The PERCEPTION questionnaire data indicated that the patients experienced significant improvements (P < 0.05) in terms of their sensations with the new prostheses. Cross-lagged data analysis did not show any causality between the OHIP-EDENT and PERCEPTION questionnaires (ZPF test, P = 0.772). We concluded that the treatment was effective with respect to the patients' QoL and their adaptation to the new prostheses. PMID- 22320247 TI - Chemiluminescence imaging immunoassay of multiple tumor markers for cancer screening. AB - A sensitive chemiluminescence (CL) imaging immunoassay method for detection of multiple tumor markers with high throughput, easy operation, and low cost was developed. The immunosensor array was prepared by covalently immobilizing capture antibodies on corresponding sensing sites on a silanized disposable glass chip. Gold nanoparticle-based bioconjugates with a high molar ratio of horseradish peroxidase (HRP) to detection antibodies were used for signal amplification. Under a sandwich immunoassay, the CL signals triggered by HRP captured on each sensing cell were collected by a charge-coupled device for simultaneous measurement of biomarkers and combination diagnosis of certain tumors. As a proof of concept, the immunosensor array was applied to detect alpha-fetoprotein, carcinoma antigen 125, carbohydrate antigen 153, and carcinoembryonic antigen and to screen patients with liver, breast, or ovarian cancers. This method showed wide linear ranges over 5 orders of magnitude and much lower detection limits than previously reported multiplexed immunoassays. The high throughput and acceptable stability, reproducibility, and accuracy showed good applicability of the proposed multiplex CL imaging immunoassay in clinical diagnosis. PMID- 22320248 TI - Examining protein surface structure in highly conserved sequence variants with mass spectrometry. AB - A simple mass spectrometry-based method capable of examining protein structure called SNAPP (selective noncovalent adduct protein probing) is used to evaluate the structural consequences of point mutations in naturally occurring sequence variants from different species. SNAPP monitors changes in the attachment of noncovalent adducts to proteins as a function of structural state. Mutations that lead to perturbations to the electrostatic surface structure of a protein affect noncovalent attachment and are easily observed with SNAPP. Mutations that do not alter the tertiary structure or electrostatic surface structure yield similar results by SNAPP. For example, bovine, porcine, and human insulin all have very similar backbone structures and no basic or acidic residue mutations, and the SNAPP distributions for all three proteins are very similar. In contrast, four variants of cytochrome c (cytc) have varying degrees of sequence homology, which are reflected in the observed SNAPP distributions. Bovine and pigeon cytc have several basic or acidic residue substitutions relative to horse cytc, but the SNAPP distributions for all three proteins are similar. This suggests that these mutations do not significantly influence the protein surface structure. On the other hand, yeast cytc has the least sequence homology and exhibits a unique, though related, SNAPP distribution. Even greater differences are observed for lysozyme. Hen and human lysozyme have identical tertiary structures but significant variations in the locations of numerous basic and acidic residues. The SNAPP distributions are quite distinct for the two forms of lysozyme, suggesting significant differences in the surface structures. In summary, SNAPP experiments are relatively easy to perform, require minimal sample consumption, and provide a facile route for comparison of protein surface structure between highly homologous proteins. PMID- 22320249 TI - Novel method to measure serum levels of des-gamma-carboxy prothrombin for hepatocellular carcinoma in patients taking warfarin: a preliminary report. AB - Des-gamma-carboxy prothrombin (DCP) is a useful tumor marker for hepatocellular carcinoma (HCC), but its utility is limited in patients taking vitamin K antagonists. We evaluated the NX-DCP ratio, a newly developed method to measure serum DCP, for its ability to identify DCP elevation induced by HCC in this patient subpopulation. Conventional DCP measurements and the NX-DCP ratio were compared in patients with and without HCC, all of whom were taking the vitamin K antagonist warfarin. We found no differences in conventional DCP measurements between patients with and without HCC due to warfarin treatment. In contrast, the NX-DCP ratio was significantly higher in patients with HCC; the NX-DCP ratio in all patients without HCC was <1.50. When the cut-off was fixed at 1.50, sensitivity and specificity for HCC diagnosis were 60.0% and 100.0%, respectively, which are comparable to those of conventional DCP measurements in patients not taking warfarin. The novel NX-DCP ratio identifies patients on warfarin with elevated DCP due to HCC and is useful as a tumor marker for HCC in this patient subpopulation. PMID- 22320250 TI - Molecular screening of alcohol and polyol adsorption onto MFI-type zeolites. AB - Configurational-bias grand canonical Monte Carlo (CB-GCMC) simulations and expanded ensemble (EE)-CB-GCMC simulations were performed to obtain adsorption isotherms of alcohols and polyols onto MFI-type zeolites from the gas phase and aqueous solution. In adsorption from both phases, Henry's constants and heats of adsorption at infinite dilution for straight-chain alcohols, diols, and triols in silicalite-1 are found to increase, and the saturation loadings decrease with increasing carbon number. Adsorption of straight-chain alcohols is more favorable than that of branched-chain alcohols. Henry's constants increase with increasing number of hydroxyl groups for gas-phase adsorption but decrease for adsorption from aqueous solution due to the strong hydrophilic solvent effect of water. The location of the hydroxyls does not affect significantly the adsorption from aqueous solution but does so in gas-phase adsorption. The saturation pressures for gas-phase adsorption decrease by orders of magnitude from the alcohols to the triols. Nonframework cations increase the adsorption of the small alcohols by an order magnitude at low concentrations (<1 mg/mL), but result in only a factor of 2 increase for larger alcohols like butanol at low concentrations (<0.03 mg/mL), and then decrease the adsorption at higher concentrations. Overall, the simulated results are in reasonable agreement with available experimental data. PMID- 22320251 TI - Single-centre experience of liver transplantation for familial amyloidotic polyneuropathy of non-Val30Met variants in Chinese patients. AB - OBJECTIVE: To review our experience of liver transplantation (LT) for patients with non-Val30Met familial amyloidotic polyneuropathy (FAP) and patients receiving FAP livers. METHOD: Data of six FAP patients and five FAP liver recipients, all Chinese, were reviewed. RESULTS: Among the six FAP patients, five patients were of the V30A variant and one patient was of the G67E variant. One patient had malnutrition. Three patients had peripheral neuropathy. Four patients had orthostatic hypotension. Five patients had cardiac involvement. Two patients underwent living-donor LT and four patients underwent deceased-donor LT. One patient had progressive cardiac and neurological involvement after transplantation. Three patients showed either improvement or a static condition. All five FAP liver recipients had hepatitis-B-related hepatocellular carcinoma before transplantation. With a median follow-up period of 49 months, all of them survived without tumour recurrence. The first recipient developed systemic transthyretin amyloidosis six years after transplantation. Upper endoscopy confirmed the presence of gastric amyloidosis, and nerve conduction test showed evidence of axonal sensorimotor polyneuropathy. CONCLUSIONS: Most of the FAP patients and FAP liver recipients displayed satisfactory outcomes after transplantation. LT halted disease progression in the FAP patients who had early presentation of the disease. PMID- 22320252 TI - Life histories have a history: effects of past and present conditions on adult somatic growth rates in wild Trinidadian guppies. AB - 1. Environmental conditions in the present, more recent past and during the juvenile stage can have significant effects on adult performance and population dynamics, but their relative importance and potential interactions remain unexplored. 2. We examined the influence of food availability at the time of sampling, 2 months prior and during the juvenile stage on adult somatic growth rates in wild Trinidadian guppies (Poecilia reticulata). 3. We found that food availability during both the early and later parts of an individual's ontogeny had important consequences for adult growth strategies, but the direction of these effects differed among life stages and their magnitude, in some cases, depended on food levels experienced during other life stages. Current food levels and those 2 months prior to growth measurements had positive effects on adult growth rate; though, food levels 2 months prior had a greater effect on growth than current food levels. In contrast, the effects of food availability during the juvenile stage were higher in magnitude but opposite in direction to current food levels and those 2 months prior to growth rate measurements. Individuals recruiting under low food levels grew faster as adults than individuals recruiting during periods of high food availability. There was also a positive interaction between food levels experienced during the juvenile stage and 2 months prior such that the effects of juvenile food level diminished as the food level experienced 2 months prior increased. 4. These results suggest that the similar conditions occurring at different life stages can have different effects on short- and long-term growth strategies of individuals within a population. They also demonstrate that, while juvenile conditions can have lasting effects on adult performance, the strength of that effect can be dampened by environmental conditions experienced as an adult. 5. A simultaneous consideration of past events in both the adult and juvenile stage may therefore improve predictions for individual- and population-level responses to environmental change. PMID- 22320253 TI - Positive technology supports shift to preventive, integrative health. PMID- 22320256 TI - Ecology and conservation biology of avian malaria. AB - Avian malaria is a worldwide mosquito-borne disease caused by Plasmodium parasites. These parasites occur in many avian species but primarily affect passerine birds that have not evolved with the parasite. Host pathogenicity, fitness, and population impacts are poorly understood. In contrast to continental species, introduced avian malaria poses a substantial threat to naive birds on Hawaii, the Galapagos, and other archipelagoes. In Hawaii, transmission is maintained by susceptible native birds, competence and abundance of mosquitoes, and a disease reservoir of chronically infected native birds. Although vector habitat and avian communities determine the geographic distribution of disease, climate drives transmission patterns ranging from continuous high infection in warm lowland forests, seasonal infection in midelevation forests, and disease free refugia in cool high-elevation forests. Global warming is expected to increase the occurrence, distribution, and intensity of avian malaria across this elevational gradient and threaten high-elevation refugia, which is the key to survival of many susceptible Hawaiian birds. Increased temperatures may have already increased global avian malaria prevalence and contributed to an emergence of disease in New Zealand. PMID- 22320257 TI - Syntheses, X-ray crystal structures, and optical, fluorescence, and nonlinear optical characterizations of diphenylphosphino-substituted bithiophenes. AB - A series of bithiophene derivatives that are either symmetrically disubstituted with two Ph(2)(X)P groups (X = O, S, Se) or monosubstituted with one Ph(2)(X)P group (X = O, S, Se) and an organic functional group (H, CHO, CH(2)OH, CO(2)Me) have been synthesized. The X-ray crystal structures of Ph(2)(Se)P(C(4)H(2)S)(2)P(Se)Ph(2), Ph(2)(O)P(C(4)H(2)S)(2)H, Ph(2)(S)P(C(4)H(2)S)(2)H, and Ph(2)(O)P(C(4)H(2)S)(2)CH(2)OH exhibit very different solid-state structures depending on the type of intermolecular pi-pi interactions that occur. The compounds have been characterized by electronic absorption and fluorescence studies. Of particular interest is that the quantum yields of Ph(2)(O)P(C(4)H(2)S)(2)H, Ph(2)(O)P(C(4)H(2)S)(2)P(O)Ph(2), Ph(2)(O)P(C(4)H(2)S)(2)CO(2)Me, and Ph(2)(O)P(C(4)H(2)S)(2)CH(2)OH are significantly larger than that of bithiophene (factors of 13, 14, 14, and 22, respectively). This behavior is quite different from that of analogously substituted terthiophenes in which substitution results in only modest increases in the quantum yields over that of terthiophene (factors of 0.94, 2.7, 1.3, and 1.5, respectively). DFT studies of the emission process suggest that modifying the Ph(2)(X)P group affects both the fluorescence and nonradiative rate constants while modifications of the organic substituents primarily affect the nonradiative rate constants. The higher quantum yields of the substituted bithiophenes make them promising for application in organic light-emitting devices (OLED). The optical power limiting (OPL) performances of these Ph(2)(X)P-substituted bithiophenes were evaluated by nonlinear transmission measurements in the violet blue spectral region (430-480 nm) with picosecond laser pulses. The OPL performances are enhanced by heavier X groups and when by higher solubilities. Saturated chloroform solutions of Ph(2)(O)P(C(4)H(2)S)(2)H and Ph(2)(S)P(C(4)H(2)S)(2)H exhibit significantly stronger nonlinear absorption than any previously reported compounds and are promising candidates for use in broadband optical power limiters. PMID- 22320258 TI - Characterization of novel RHD alleles: relationship between phenotype, genotype, and trimeric architecture. AB - BACKGROUND: RH1 is one of the most clinically important blood group antigens in the field of transfusion and prevention of fetomaternal incompatibilities. New variant RHD alleles are regularly identified and their characterization is essential to ensuring patient safety. STUDY DESIGN AND METHODS: Blood samples with uncertain RhD phenotypes not resolved by our first-line SNaPshot assay were sequenced for all 10 RHD exons. RHD zygosity was investigated. Flow cytometry was performed to determine RhD antigen density and epitope pattern. RESULTS: Seven novel RHD alleles were identified. Six, that is, RHD(T55P), RHD(A85G), RHD(G132R), RHD(G132E), RHD(D403V), and DAR(T203A), resulted from nucleotide polymorphisms. The seventh, that is, RHD(S182WfsX46), resulted from a 4-bp deletion that led to a reading frame shift and the appearance of a premature stop codon. Study of RhD expression of the first five alleles at hemizygous state showed greatly reduced antigen densities ranging from 50 to 618 antigens per red blood cell (RBC). DAR(T203A) was classified as a partial D antigen with a weakened reactivity profile similar to that of DAR. As expected, no D antigen was detected on RBCs carrying the RHD(S182WfsX46) allele. In parallel, RhD expression of RHD(G336R)/weak D type 58, RHD(F410V), and suspected RHD(1-9)-CE was determined to be less than or equal to 50 antigens per RBC. RhAG/RhD(2) trimer model supports the observed phenotypes. CONCLUSION: Although the frequency of the new RHD alleles presented herein is low, their phenotypic and genotypic description adds to the repertoire of reported RHD alleles. These data can be useful for optimization of molecular screening tools. PMID- 22320259 TI - Effects of organic solvent and crystal water on gamma-chymotrypsin in acetonitrile media: observations from molecular dynamics simulation and DFT calculation. AB - The use of enzymes in nonaqueous solvent has been one of the most exciting facets of enzymology in recent times; however, the mechanism of how organic solvent and essential water influence on structure and function of enzyme has been not satisfactorily explained in experiments, which limit its further application. Herein, we used molecular dynamics (MD) simulation to study gamma-chymotrypsin in two types of media (viz., acetonitrile media with inclusion of 151 crystal water molecules and aqueous solution). On the basis of the MD result, the truncated active site modes containing two specific solvent molecules are furthered studied at the B3LYP/6-31+G(d,p) level of theory within the framework of PCM model. The results show that the acetontrile solvent gives rise to an extent deviation of enzyme structure from the native one, a drop in the flexibility and the total SASA of enzyme. The QM study further reveals that the structure variation of the active pocket caused by acetonitrile would lead to a weakened strength in the catalytic H-bond network, a drop in the pK(a) value of His57, and an increase in the proton transfer barriers from the Ser195 to the His57 residue, which may contribute to the drop in the enzymatic activity in acetontrile media. In addition, the crystal waters play an importance role in retaining the catalytic H bond network and weakening the acetonitrile-induced variations above, which may be associated with the fact that the enzyme could retain catalytic activity in microhydration acetonitrile media. PMID- 22320260 TI - Integrating medical, assistive, and universally designed products and technologies: assistive technology device classification (ATDC). AB - INTRODUCTION: ISO26000:2010 International Guidance Standard on Organizational Social Responsibility requires that effective organizational performance recognize social responsibility, including the rights of persons with disabilities (PWD), engage stakeholders and contribute to sustainable development. Millennium Development Goals 2010 notes that the most vulnerable people require special attention, while the World Report on Disability 2011 identifies improved data collection and removal of barriers to rehabilitation as the means to empower PWD. BACKGROUND: The Assistive Technology Device Classification (ATDC), Assistive Technology Service Method (ATSM) and Matching Person and Technology models provide an evidence-based, standardized, internationally comparable framework to improve data collection and rehabilitation interventions. The ATDC and ATSM encompass and support universal design (UD) principles, and use the language and concepts of the International Classification of Functioning, Disability and Health (ICF). PURPOSE: Use ATDC and ICF concepts to differentiate medical, assistive and UD products and technology; relate technology "types" to markets and costs; and support provision of UD products and technologies as sustainable and socially responsible behavior. CONCLUSION: Supply-side and demand-side incentives are suggested to foster private sector development and commercialization of UD products and technologies. Health and health-related professionals should be knowledgeable of UD principles and interventions. PMID- 22320261 TI - Optimal body fat percentage cut-offs for obesity in Chinese adults. AB - Obesity results in an increased risk of metabolic syndrome (MetS) and Type 2 diabetes (T2DM). Body fat percentage (BF%) is a common index of body composition. The aim of the present study was to determine the optimal BF% cut-offs for obesity to predict MetS and T2DM in Chinese adults. The baseline study group comprised 3916 Chinese adults (age 30-70 years of age); 2033 subjects without MetS or T2DM were followed up for a maximum of 5.5 years. The BF% was estimated using bioelectrical impedance analysis. Optimal BF% cut-offs were analysed by receiver operating characteristic (ROC) curves. Binary logistic regression analysis was performed to measure the association between obesity at baseline defined by BF% and newly developed MetS and T2DM. Mean BF% levels were lower in men than in women (23.9 +/- 6.1% vs 33.5 +/- 7.1%, respectively; P < 0.01). For men, the optimal BF% cut-offs for the prediction of MetS and T2DM were 25.45% and 26.65%, respectively; for women, the corresponding values were 34.95% and 36.55%. Subjects with high BF% (>= 25% in men; >= 35% in women) had higher risks of incident MetS or T2DM than those with low BF% (< 25% in men; < 35% in women). The relative risks were 3.43 (95% confidence intervals (CI) 2.59-4.54) and 2.92 (95% CI 1.85-4.60), respectively. The optimal BF% cut-offs for obesity for the prediction of MetS and T2DM in Chinese men and women were around 25% and 35%, respectively. PMID- 22320262 TI - Cytokine and chemokine modification by Toll-like receptor polymorphisms is associated with nasopharyngeal carcinoma. AB - Toll-like receptors (TLR) play a pivotal role in sensing a wide range of pathogens, including bacteria, fungi and viruses. A dysregulation of TLR signaling may increase the risk of developing chronic inflammatory diseases and cancers. The aim of this study was to investigate the association of TLR2 R753Q, TLR4 D299G, and T399I polymorphisms with nasopharyngeal carcinoma (NPC) and to explore the effects of these polymorphisms on cytokine and chemokine expression in NPC biopsies. The genotypes of the three loci among 236 patients with NPC and 287 healthy controls were determined by PCR-RFLP. Cytokines and chemokines mRNA and protein in NPC biopsies were measured by real-time quantitative PCR and ELISA, respectively. Results showed that the combined CT/TT genotype of T399I was associated with increased NPC risk, with an odds ratio of 1.853 (95% confidence interval: 1.184-2.961). Also, individuals with the T allele of T399I showed a 1.842-fold increase in NPC risk compared to those with the T399I C allele (95% confidence interval: 1.213-3.015). Messenger RNA levels of interleukin (IL) 1alpha, tumor necrosis factor-alpha and IL-10 were significantly elevated in patients with T399I combined CT/TT genotype; IL-1alpha and IL-10 protein concentration significantly increased in NPC patients with T399I combined CT/TT genotype compared to those with the T399I CC genotype. Our data suggest that TLR4 T399I modify cytokines and chemokines patterns and play a role in the development of NPC. PMID- 22320263 TI - Improved complementary polymer pair system: switching for enzyme activity by PEGylated polymers. AB - The development of technology for on/off switching of enzyme activity is expected to expand the applications of enzyme in a wide range of research fields. We have previously developed a complementary polymer pair system (CPPS) that enables the activity of several enzymes to be controlled by a pair of oppositely charged polymers. However, it failed to control the activity of large and unstable alpha amylase because the aggregation of the complex between anionic alpha-amylase and cationic poly(allylamine) (PAA) induced irreversible denaturation of the enzyme. To address this issue, we herein designed and synthesized a cationic copolymer with a poly(ethylene glycol) backbone, poly(N,N-diethylaminoethyl methacrylate) block-poly(ethylene glycol) (PEAMA-b-PEG). In contrast to PAA, alpha-amylase and beta-galactosidase were inactivated by PEAMA-b-PEG with the formation of soluble complexes. The enzyme/PEAMA-b-PEG complexes were then successfully recovered from the complex by the addition of anionic poly(acrylic acid) (PAAc). Thus, dispersion of the complex by PEG segment in PEAMA-b-PEG clearly plays a crucial role for regulating the activities of these enzymes, suggesting that PEGylated charged polymer is a new candidate for CPPS for large and unstable enzymes. PMID- 22320264 TI - Negative chemical ionization GC/MS determination of nitrite and nitrate in seawater using exact matching double spike isotope dilution and derivatization with triethyloxonium tetrafluoroborate. AB - The alkylation of nitrite and nitrate by triethyloxonium tetrafluoroborate allows determination of their ethyl esters by headspace gas chromatography/mass spectrometry (GC/MS). In the present study, significant improvement in analytical performance is achieved using negative chemical ionization providing detection limits of 150 ng/L for NO(2)(-) and 600 ng/L for NO(3)(-), an order of magnitude better than those achieved using electron impact ionization. The derivatization procedure was optimized and alkaline conditions adopted to minimize conversion of nitrite to nitrate (determined to be 0.07% at 100 mg/L NO(2)(-)) and to avoid the exchange of oxygen between the analytes and the solvent (water). Quantitation entails use of isotopically enriched standards (N(18)O(2)(-) and (15)NO(3)(-)), which also permits monitoring of potential conversion from nitrite to nitrate during the analysis (double spike isotope dilution). PMID- 22320265 TI - Assessing urine human papillomavirus polymerase chain reaction testing as a tool for screening anal HPV infection in HIV-positive MSM. AB - Multiple types of human papillomavirus (HPV) are responsible for most cervical cancers but also cause anal cancers-especially in HIV-positive patients. Furthermore, men who have sex with men (MSM) are twice as likely to develop anal cancers as non-MSM. A simple screening test for HPV infection would be useful in these patients. The aim of our study was to evaluate the detection of HPV by real time polymerase chain reaction (PCR) in urine as a marker of anal infection in MSM. The study included 52 HIV-positive MSM treated at Amiens University Hospital (Amiens, France). After obtaining informed consent, we performed an anal swab and gathered 10 mL of first-void urine. Samples were extracted and amplified in a real-time PCR. Genotypes were determined with a PapilloCheck((r)) system (Greiner Bio-One, Frickenhausen, Germany). The anal test was the gold standard for calculating the characteristics of the urine test. The sensitivity of the urine test for diagnosing anal HPV infection was 15%, the specificity was 66%, the positive predictive value was 87.5%, and negative predictive value was 4.5%. The prevalence of anal HPV infection in the study population was 94%. Genotype 42 was the most common. The anal HPV viral load was significantly lower in men in a stable relationship than in single men. However, there was no statistically significant relationship between anal viral load and anal intraepithelial lesions. We conclude that urine-based HPV is a poor predictor of anal HPV infection in HIV-positive MSM. PMID- 22320266 TI - Medication-related barriers to entering HIV care. AB - Early entry to HIV care and receipt of antiretroviral therapy improve the health of the individual and decrease the risk of transmission in the community. To increase the limited information on prospective decisions to enter care and how these decisions relate to beliefs about HIV medications, we analyzed interview data from the Never in Care Project, a multisite project conducted in Indiana, New Jersey, New York City, Philadelphia, and Washington State. From March 2008 through August 2010, we completed structured interviews with 134 persons with no evidence of HIV care entry, 48 of whom also completed qualitative interviews. Many respondents believed that HIV care entails the passive receipt of medications that may be harmful or unnecessary, resulting in reluctance to enter care. Respondents voiced concerns about prescription practices and preserving future treatment options, mistrust of medications and medical care providers, and ambivalence about the life-preserving properties of medications in light of an assumed negative impact on quality of life. Our results support the provision of information on other benefits of care (beyond medications), elicitation of concerns about medications, and assessment of psychosocial barriers to entering care. These tasks should begin at the time a positive test result is delivered and continue throughout the linkage-to-care process; for persons unwilling to enter care immediately, support should be provided in nonmedical settings. PMID- 22320267 TI - Differential MyD88/IRAK4 requirements for cross-priming and tumor rejection induced by heat shock protein 70-model antigen fusion protein. AB - Priming of CD8(+) T cells requires two signals, one produced by T-cell receptor recognition of antigen, and a second that is often provided by the innate immune response. In this context, antigens non-covalently or covalently associated with heat shock proteins (HSP) are internalized and processed in antigen-presenting cells (APC) to be presented by MHC I molecules to CD8(+) T cells, thus, signal 1 has been well characterized in this pathway of cross-presentation. Signal 2 is not fully understood, although there are reports that Toll-like receptors (TLRs) interact with HSP and activate APC. The ability of HSP to activate APC through TLRs is, however, controversial because of the possibility of endotoxin contamination. Using a variety of TLR KO mice, we present evidence that TLRs (TLR2, 3, 4, 7, and 9) and their adaptor molecules MyD88 and IRAK4 are dispensable in cross-priming by a mycobacterial HSP70-antigen (ovalbumin as a model antigen) fusion protein; in contrast, MyD88/IRAK4, but not TLRs, are required for tumor rejection induced by the same reagent. Our results indicate that HSP-mediated cross-priming uses a second signal produced by mechanisms other than TLR cascades. We hypothesize that efficient cross-priming by HSP70 alone is insufficient for tumor rejection and that MyD88/IRAK4-dependent inflammatory stimulation, which might contribute to maintenance of the initially primed effector cells, is required to eradicate tumor burden. PMID- 22320268 TI - Characterization of HmqF, a protein involved in the biosynthesis of unsaturated quinolones produced by Burkholderia thailandensis. AB - The opportunistic pathogen Burkholderia thailandensis produces a number of structurally similar unsaturated quinolones involved in quorum sensing. However, little is known about the biosynthesis of these unsaturated quinolones. In this study, we have characterized the starting point of the biosynthesis of unsaturated quinolone molecules produced in B. thailandensis. We have shown by using in vitro enzymology, liquid chromatography, and mass spectrometry that protein HmqF is involved in the biosynthesis of unsaturated quinolones produced by B. thailandensis. HmqF consists of three domains: an adenylation domain (A domain), a dehydrogenase domain (DH domain), and an acyl carrier domain (ACP). The three domains (A, DH, and ACP) were cloned and expressed individually in Escherichia coli, and their reactivity was studied using high-performance liquid chromatography (HPLC) and mass spectrometry (MS) based assays. Our in vitro studies show that the A domain catalyzes ATP-dependent activation of medium chain (C6-C14) fatty acids without activation by coenzyme A (CoA). Results from competition assays are consistent with decanoic acid being the preferred substrate. Incubation of the ACP domain with 4'-phosphopantetheine transferase and CoA led to the formation of phosphopantetheinylated ACP (Ppant-ACP). In a Ppant ejection assay using tandem MS (MS/MS), a mass consistent with the mass of a cyclic variant of dephosphorylated Ppant was detected. We further demonstrated that Ppant-ACP could be loaded with medium chain fatty acids in the presence of ATP and the A domain. MS analysis was consistent with the formation of Ppant-ACP thiol esters of the fatty acids. MS/MS Ppant ejection experiments confirmed the loss of 2H in samples of fatty acid-loaded Ppant-ACP in the presence of the DH domain. HPLC analysis of benzyl amide ligation products allowed us to conclude that dehydrogenation produced trans-beta,gamma-unsaturation in the fatty acid chains. Our results are in good agreement with naturally observed quinolone molecules produced by B. thailandensis, which predominately produce nine-carbon trans-beta,gamma-unsaturated alkyl chain quinolone molecules. PMID- 22320269 TI - Patients need patience. PMID- 22320270 TI - Universal post-arrival screening for child refugees in Australia: isn't it time? AB - It is known that the refugee population in Australia is at risk of tuberculosis (TB) and children with TB infection can develop active disease with devastating consequence. Currently, in New South Wales (NSW) and possibly other Australian States and Territories, there are different and complex health-screening pathways for newly arrived refugees. This is compounded by various factors, such as social and language difficulties for refugees to access healthcare and limited pre embarkation screening. In this Viewpoint article, we present a child refugee in Australia with TB and use this case to reason why a universal post-arrival health screening programme should be established. PMID- 22320271 TI - Sleep and academic performance in Indigenous Australian children from a remote community: an exploratory study. AB - AIM: Disruptions to sleep in childhood are associated with poor behaviour and deficits in academic performance and executive function. Although academic performance of indigenous children from remote communities in Australia is documented as well below that of non-indigenous children, the extent of sleep disruption and its contribution to academic performance among this population has not been assessed. This pilot study aimed to objectively assess the sleep of remote indigenous children and the association between sleep disruption and both academic performance and executive function. METHOD: Twenty-one children from a remote Australian indigenous community aged 6-13 years wore actigraphy for two consecutive nights, reported subjective sleepiness, and were objectively assessed for academic performance (Wechsler Individual Achievement Test, 2nd Edition) and executive function (NEuroloPSYcological Assessment-II). RESULTS: Results show marked reduction in sleep time, sleep fragmentation, academic performance and auditory attention compared with non-indigenous norms. Sleep duration was not associated with performance, possibly because of reduced sleep and performance observed across the entire group. Sleep fragmentation was associated with reduced reading and numerical skills (P < 0.05). CONCLUSIONS: The sleep of indigenous children in remote communities is an important area of future inquiry, and our initial findings of poor sleep and an association between sleep disruption and academic performance may have important implications for intervention strategies aimed at 'closing the gap'. Further studies should assess a broader range of demographic, social and economic factors to better understand the associations reported here and guide future intervention. PMID- 22320272 TI - Swiss-cheese appearance of the brain. PMID- 22320273 TI - The role of steroids in children with multiple recurrences of intussusception. AB - We describe the case of a boy who had 9 recurrences of intussusception, for which no pathological lesion at the leadpoint was identified. A contrast follow-through study revealed a follicular/nodular mucosal pattern, particularly prominent in the terminal ileum and caecum. Patients with multiple recurrences usually have an identifiable lesion at the leadpoint, but sometimes recurrences may be due to lymphoid hyperplasia, as presumed in our case. No further recurrences occurred after a two month tapering course of oral prednisolone. PMID- 22320275 TI - A strawberry in the nose. PMID- 22320276 TI - Cutaneous lesions in transient abnormal myelopoiesis. PMID- 22320277 TI - The views of Chinese parents on research participation and informed consent. PMID- 22320279 TI - Intolerance to food additives - does it exist? AB - 'Food intolerance' is often confused with a range of adverse symptoms which may be coincidental to ingestion of food. 'Food intolerance' is defined as a reaction in which symptoms must be objectively reproducible and not known to involve an immunological mechanism. A more precise term is non-allergic food hypersensitivity, which contrasts with food allergies which are due to an immunological mechanism. Some children will experience food reactions to food additives. Reported symptoms range from urticaria/angioedema to hyperactive behaviours. While parents/carers report that over one fifth of children experience of food reaction, only 1 in 20 of these are confirmed to have a non allergic food hypersensitivity on testing. PMID- 22320280 TI - Chromosome microarray in Australia: a guide for paediatricians. AB - Chromosomal microarray or molecular karyotype has become the first-line genetic investigation for children with intellectual disability, autistic spectrum disorder or multiple congenital anomalies. Chromosomal microarray increases the detection rate of pathogenic chromosome imbalances including submicroscopic deletions or duplications in patients with undiagnosed intellectual disability to approximately 15% compared with 3% with conventional cytogenetics. This review article summarises the diagnostic technique and highlights the advantages and limitations of chromosomal microarray. Our aim is to assist clinicians in providing pretest counselling and with interpretation of the result. PMID- 22320281 TI - PLP1 duplication at the breakpoint regions of an apparently balanced t(X;22) translocation causes Pelizaeus-Merzbacher disease in a girl. AB - PLP1 (proteolipid protein1 gene) mutations cause Pelizaeus-Merzbacher disease (PMD), characterized by hypomyelination of the central nervous system, and affecting almost exclusively males. We report on a girl with classical PMD who carries an apparently balanced translocation t(X;22)(q22;q13). By applying array based comparative genomic hybridization (a-CGH), we detected duplications at 22q13 and Xq22, encompassing 487-546 kb and 543-611 kb, respectively. The additional copies were mapped by fluorescent in situ hybridization to the breakpoint regions, on the derivative X chromosome (22q13 duplicated segment) and on the derivative 22 chromosome (Xq22 duplicated segment). One of the 14 duplicated X-chromosome genes was PLP1.The normal X chromosome was the inactive one in the majority of peripheral blood leukocytes, a pattern of inactivation that makes cells functionally balanced for the translocated segments. However, a copy of the PLP1 gene on the derivative chromosome 22, in addition to those on the X and der(X) chromosomes, resulted in two active copies of the gene, irrespective of the X-inactivation pattern, thus causing PMD. This t(X;22) is the first constitutional human apparently balanced translocation with duplications from both involved chromosomes detected at the breakpoint regions. PMID- 22320282 TI - Static micromixer-coaxial electrospray synthesis of theranostic lipoplexes. AB - Theranostic lipoplexes are an integrated nanotherapeutic system with diagnostic imaging capability and therapeutic functions. They hold great promise to improve current cancer treatments; however, producing uniform theranostic lipoplexes with multiple components in a reproducible manner is a highly challenging task. Conventional methods, such as bulk mixing, are not able to achieve this goal because of their macroscale and random nature. Here we report a novel technique, called the static micromixer-coaxial electrospray (MCE), to synthesize theranostic lipoplexes in a single step with high reproducibility. In this work, quantum dots (QD605) and Cy5-labeled antisense oligodeoxynucleotides (Cy5-G3139) were chosen as the model imaging reagent and therapeutic drug, respectively. Compared with bulk mixing, QD605/Cy5-G3139-loaded lipoplexes produced by MCE were highly uniform with polydispersity of 0.024 +/- 0.006 and mean diameter by volume of 194 +/- 15 nm. MCE also showed higher encapsulation efficiency of QD605 and Cy5-G3139. QD605 and Cy5 also formed the Forster resonance energy transfer pair, and thus the cellular uptake and intracellular fate of theranostic lipoplexes could be visualized by flow cytometry and confocal microscopy. The lipoplexes were efficiently delivered to A549 cells (non-small cell lung cancer cell line) and down-regulated the Bcl-2 gene expression by 48 +/- 6%. PMID- 22320283 TI - Contemporary profile of oral manifestations of HIV/AIDS and associated risk factors in a Southeastern US clinic. AB - BACKGROUND: Introduction of highly active antiretroviral therapy (HAART) has resulted in a significant decrease of oral manifestations (OMs). The profile and risk factors for OM in those individuals initiating HAART remain understudied in the Southeast of the United States, region of increasing HIV prevalence. OBJECTIVE: To determine clinical, socio-demographic, and laboratory characteristics associated with the presence of OM among patients initiating HAART. METHODS: Retrospective review of electronically captured data from patients initiating HAART at a Southeastern US clinic. Prevalence was determined, and risk factors for overall OM, oropharyngeal candidiasis (OPC), and all other OM were evaluated using logistic regression. RESULTS: In our sample (n = 744), majority of individuals were males (75 percent), African-American (50 percent), mean age of 39 years, 42 percent of which reported sex with men (MSM). Two hundred sixty-six had some type of OM. Compared with those without any OM, patients with OM had a lower mean baseline CD4+ T cells count (CD4 count) (331 +/ 260 versus 179 +/- 244 CD4 cells/mm(3) ) and higher mean baseline HIV-1 RNA viral load (4.0 +/- 1.34 log(10) versus 4.6 +/- 1.30 log(10) ) (P < 0.01). In the logistic regression models seeking to determine factors associated with an increased risk of OM and OPC, the only characteristic associated with the outcome was baseline CD4 value. Being male, African-American, and heterosexual showed a protective role for OM other than OPC. CONCLUSION: OM continues to be common despite HAART. General OM and OPC were closely associated with a low baseline CD4 count. Knowledge of risk factors for OM can potentially help clinicians target oral evaluation of HIV-positive individuals. PMID- 22320284 TI - Treatment decisions for deep carious lesions in the Public Health Service in Southern Brazil. AB - OBJECTIVES: The aim of the present study was to assess Public Health Service clinicians' treatment decisions about deep carious lesions in the city of Porto Alegre, Brazil. METHODS: Treatment decisions were assessed with a structured questionnaire (open/discursive and containing information about gender, university and year of college graduation, and college major) and three simulated clinical cases composed of teeth with primary deep carious lesion. All professionals working for the Public Health Service in the city were addressed. RESULTS: Out of 122 professionals, 54 participated in the study (response rate of 44 percent). There was no difference between respondents and non-respondents regarding gender, year of college graduation, or college major. The most commonly indicated procedure was direct complete excavation (71.1 percent), followed by stepwise excavation (17.6 percent), partial caries removal (8.8 percent), and pulp therapies (direct pulp capping, partial or complete pulpotomy, and endodontics) (2.5 percent). Year of college graduation was the only variable influencing treatment decision. Logistic regression analysis showed that professionals who had graduated after the year 2000 were significantly more likely to indicate a conservative treatment than were dentists who graduated through 1979 (odds ratio = 5.5). CONCLUSIONS: The most commonly proposed treatment is the one with the highest risk of pulp exposure, and consequently the poorest prognosis. Younger dentists tended to indicate more conservative approaches, compared with those indicated by older dentists. PMID- 22320285 TI - Dentists' familiarity with tobacco cessation programs in dental settings in Iran. AB - OBJECTIVES: The current study assessed Iranian dentists' practice, knowledge, perceived barriers, and attitudes toward helping patients to quit. We hypothesized that Iranian dentists would have limited knowledge and awareness of tobacco cessation methods or of their important role in encouraging patients to quit. We expected the combination of quantitative and qualitative research to yield important insights regarding effective methods of engaging Iranian dentists in tobacco intervention. METHODS: From a list of registered dentists following an initial screening, we randomly selected a total of 1,000 dental practices in 10 randomly selected provinces. Following an initial letter describing the study, we mailed a questionnaire. For the qualitative part of the study, we used a convenience purposeful sampling of 16 dentists. RESULTS: Despite repeated contacts, only 35 percent of those contacted returned completed surveys. Key findings not only included generally positive attitudes toward tobacco cessation programs, but also identification of major barriers including concerns about patient resistance, lack of supportive organization, and opportunities for training. Dentists were far more likely to ask patients about smoking than to provide actual cessation support. Female dentists were more likely to ask patients. The qualitative interviews shed further light on barriers to intervention. CONCLUSIONS: Interpretation of the findings is limited by the relatively low response rate. However, despite identified barriers to intervention, we are encouraged by dentists' overall knowledge and interest in tobacco cessation services. We plan to use the current findings to inform development of continuing education programs and incorporation of tobacco cessation counseling into dental school curricula in Iran. PMID- 22320286 TI - Chronicling the dental therapist movement in the United States. AB - There have been three attempts to introduce dental therapists (DTs) to the US dental workforce. This account will review early failed attempts to develop DTs, the recent successful Alaska initiative, the Minnesota legislature's authorization of DTs, state dental associations' deliberations on therapists in the workforce, and the efforts of national advocacy groups, foundations, and state legislatures to promote workforce innovation. It concludes with a discussion of the opposition to therapists from elements of organized dentistry. PMID- 22320287 TI - Longitudinal associations between children's dental caries and risk factors. AB - Dental caries is a common disease in children of all ages. It is desirable to know whether children with primary, mixed, and permanent dentitions share risk factors for cavitated and non-cavitated caries. OBJECTIVE: To assess the longitudinal associations between caries outcomes and modifiable risk factors. METHODS: One hundred and fifty-six children in the Iowa Fluoride Study met inclusion criteria of three dental examinations and caries-related risk factor assessments preceding each examination. Surface-specific counts of new non cavitated caries and cavitated caries at the primary (Exam 1: age 5), mixed (Exam 2: age 9) and permanent (Exam 3: age 13) dentition examinations were outcome variables. Explanatory variables were caries-related factors, including averaged beverage exposure frequencies, tooth brushing frequencies, and composite water fluoride levels collected from 3-5, 6-8, and 11-13 years, dentition category, socioeconomic status, and gender. Generalized linear mixed models (GLMMs) were used to explore the relationships between new non-cavitated or cavitated caries and caries-related variables. RESULTS: Greater frequency of 100 percent juice exposure was significantly associated with fewer non-cavitated and cavitated caries surfaces. Greater tooth brushing frequency and high socioeconomic status (SES) were significantly associated with fewer new non-cavitated caries. Children had significantly more new cavitated caries surfaces at the mixed dentition examination than at the primary and permanent dentition examinations. CONCLUSIONS: There were common caries-related factors for more new non-cavitated caries across the three exams, including less frequent 100 percent juice exposure, lower tooth brushing frequency and lower SES. Less frequent 100 percent juice exposures might be associated with higher exposures to several other cariogenic beverages. PMID- 22320288 TI - Body mass index measurement in schools: partnering with oral health. AB - OBJECTIVES: The purpose of this review was to examine methodological similarities and differences in states that have implemented joint school-based oral health/body mass index (BMI) surveillance. METHODS: Individuals in states with joint oral health/BMI surveillance were interviewed by e-mail and phone on the following: how the collaboration came about, survey methodology, rewards for participation, BMI data collection methods, data forms, BMI results, how BMI data were utilized, lessons learned, and challenges. RESULTS: Nine states were represented in this review (Colorado, Georgia, Illinois, Maine, New Hampshire, North Dakota, Ohio, Wisconsin, and Wyoming). All states collected surveillance data among third-grade children through selecting a random, stratified sample of elementary schools. These states also used state-specific BMI protocols, including use of standardized, calibrated equipment to measure height/weight. Many states also used local support to implement the surveillance program and used external sources for statistical support. Differences among these states included types of rewards used, mode of consent, and parties involved in the collaboration. The most common uses of the BMI data include: assessing the magnitude of the problem, informing programs, allocation of resources, identification of priority areas for prevention research, support for grant applications, and program evaluation. CONCLUSIONS: Although there are some minor differences among states that have implemented joint school-based oral health/BMI surveillance, there are overarching similarities such as survey design and standardization of BMI measures. States considering implementing BMI surveillance efforts can use this review as a starting point to consider attributes such as program effectiveness and methods to improve or enhance surveillance systems already in place. PMID- 22320289 TI - Oral health among white, black, and Mexican-American elders: an examination of edentulism and dental caries. AB - OBJECTIVES: To examine racial/ethnic disparities in oral health among older Americans. METHODS: Differences in frequency of edentulism and number of decayed, missing, and filled teeth were assessed in 2,679 non-Hispanic white, 742 non Hispanic black, and 934 Mexican-American individuals aged 60 and older from the National Health and Nutrition Examination Survey (1999-2004). RESULTS: Controlling for potential confounding variables, blacks and Mexican-Americans had significantly higher numbers of decayed teeth but fewer numbers of filled teeth than whites. Although blacks had a lower likelihood of being edentulous than whites, dentate blacks had a higher number of missing teeth. Compared with whites, Mexican-Americans were less likely to be edentulous, and dentate Mexican Americans had fewer missing teeth. Our study also showed that blacks and Mexican Americans had less frequent dental checkups than whites. CONCLUSIONS: Oral health disparities are persistent across racial/ethnic groups for older Americans despite the fact that the differences between groups typically diminish when socioeconomic, health-related, and behavioral factors are considered in the models. Our study suggests that reducing racial/ethnic oral health disparities requires multiple clinical approaches. PMID- 22320290 TI - Amount and type of alcohol consumption and missing teeth among community-dwelling older adults: findings from the Copenhagen Oral Health Senior study. AB - OBJECTIVES: To study if an association between total weekly intake of alcohol, type-specific weekly alcohol intake, alcoholic beverage preference, and the number of teeth among older people exists. METHODS: A cross-sectional study including a total of 783 community-dwelling men and women aged 65-95 years who were interviewed about alcohol drinking habits and underwent a clinical oral and dental examination. Multiple regression analyses were applied for studying the association between total weekly alcohol consumption, beverage-specific alcohol consumption, beverage preference (defined as the highest intake of one beverage type compared with two other types), and the number of remaining teeth (<= 20 versus >20 remaining teeth). RESULTS: The odds ratio (OR) of having a low number of teeth decreased with the total intake of alcohol in women, with ORs for a low number of teeth of 0.40 [95 percent confidence interval (CI) 0.22-0.76] in women drinking 1-14 drinks per week and 0.34 (95 percent CI 0.16-0.74) in women with an intake of more than 14 drinks per week compared with abstainers. Similar relations could also be obtained for type-specific alcohol intake of wine and for wine and spirits preference among women. Men who preferred beer showed a decreased risk for a low number of teeth compared with men with other alcohol preferences. CONCLUSION: In this study, alcohol consumption, wine drinking, and wine and spirits preference among women were associated with a higher number of teeth compared with abstainers. Among men, those who preferred beer also had a higher number of teeth. PMID- 22320291 TI - Income, dental insurance coverage, and financial barriers to dental care among Canadian adults. AB - OBJECTIVES: To explore the issue of affordability in dental care by assessing associations between income, dental insurance, and financial barriers to dental care in Canadian adults. METHODS: Data were collection from a national sample of adults 18 years and over using a telephone interview survey based on random digit dialing. Questions were asked about household income and dental insurance coverage along with three questions concerning cost barriers to accessing dental care. These were: "In the past three years...has the cost of dental care been a financial burden to you?...have you delayed or avoided going to a dentist because of the cost?...have you been unable to have all of the treatment recommended by your dentist because of the cost?" RESULTS: The survey was completed by 2,027 people, over half of which (56.0%) were covered by private dental insurance and 4.9 percent by public dental programs. The remainder, 39.1 percent, paid for dental care out-of-pocket. Only 19.3 percent of the lowest income group had private coverage compared with 80.5 percent of the highest income group (P < 0.001). Half (48.2%) responded positively to at least one of the three questions concerning cost barriers, and 14.8 percent responded positively to all three. Low income subjects (P < 0.001) and those without dental insurance (P < 0.001) were most likely to report financial barriers to care. While private dental insurance reduced financial barriers to dental care, it did not entirely eliminate it, particularly for those with low incomes. Those reporting such barriers visited the dentist less frequently and had poorer oral health outcomes after controlling for the effects of income and insurance coverage. CONCLUSIONS: Canadian adults report financial barriers to dental care, especially those of low income. These barriers appear to have negative effects with respect to dental visiting and oral health outcomes. For policy, appropriateness will be key, as clarity needs to be established in terms of what constitutes actual need, and thus which dental services can then be considered a public health response to affordability. PMID- 22320292 TI - Examiner training and reliability in two randomized clinical trials of adult dental caries. AB - OBJECTIVES: This report describes the training of dental examiners participating in two dental caries clinical trials and reports the inter- and intra-examiner reliability scores from the initial standardization sessions. METHODS: Study examiners were trained to use a modified International Caries Detection and Assessment System II system to detect the visual signs of non-cavitated and cavitated dental caries in adult subjects. Dental caries was classified as no caries (S), non-cavitated caries (D1), enamel caries (D2), and dentine caries (D3). Three standardization sessions involving 60 subjects and 3,604 tooth surface calls were used to calculate several measures of examiner reliability. RESULTS: The prevalence of dental caries observed in the standardization sessions ranged from 1.4 percent to 13.5 percent of the coronal tooth surfaces examined. Overall agreement between pairs of examiners ranged from 0.88 to 0.99. An intra class coefficient threshold of 0.60 was surpassed for all but one examiner. Inter examiner unweighted kappa values were low (0.23-0.35), but weighted kappas and the ratio of observed to maximum kappas were more encouraging (0.42-0.83). The highest kappa values occurred for the S/D1 versus D2/D3 two-level classification of dental caries, for which seven of the eight examiners achieved observed to maximum kappa values over 0.90. Intra-examiner reliability was notably higher than inter-examiner reliability for all measures and dental caries classifications employed. CONCLUSION: The methods and results for the initial examiner training and standardization sessions for two large clinical trials are reported. Recommendations for others planning examiner training and standardization sessions are offered. PMID- 22320293 TI - Fluorine transfer to alkyl radicals. AB - The development of new synthetic technologies for the selective fluorination of organic compounds has increased with the escalating importance of fluorine containing pharmaceuticals. Traditional methods potentially applicable to drug synthesis rely on the use of ionic forms of fluorine (F(-) or F(+)). Radical methods, while potentially attractive as a complementary approach, are hindered by a paucity of safe sources of atomic fluorine (F(*)). A new approach to alkyl fluorination has been developed that utilizes the reagent N fluorobenzenesulfonimide as a fluorine transfer agent to alkyl radicals. This approach is successful for a broad range of alkyl radicals, including primary, secondary, tertiary, benzylic, and heteroatom-stabilized radicals. Furthermore, calculations reveal that fluorine-containing ionic reagents are likely candidates for further expansion of this approach to polar reaction media. The use of these reagents in alkyl radical fluorination has the potential to enable powerful new transformations that otherwise would take multiple synthetic steps. PMID- 22320294 TI - Dihydro-alkoxyl-benzyl-oxopyrimidine derivatives (DABOs) as non-nucleoside reverse transcriptase inhibitors: an update review (2001-2011). AB - Numerous structurally different non-nucleoside compounds have been evaluated for their inhibitory effects against HIV replication, in which DABO derivatives, bearing the dihydro-alkoxyl-benzyl-oxopyrimidine scaffold, have been identified as a particular class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). The S-DABO, NH-DABO, -N-DABO, DATNO and DACO analogs represent various structural chemical modifications of the substituents on C2, C6 and C5 of the pyrimidine ring to obtain potentially higher potency and lower cytotoxicity. This review article describes the recent progress of the chemical modifications and structure-activity relationship studies of DABO derivatives and provides new clues for the design of new DABO congeners. PMID- 22320295 TI - Targeting mitogen-activated protein kinase phosphatase-1 (MKP-1): structure-based design of MKP-1 inhibitors and upregulators. AB - Mitogen-activated protein kinase phosphatases (MKPs) are dual specificity protein phosphatases (DUSPs) that dephosphorylate both phospho-tyrosine and phospho threonine residues on mitogen-activated protein kinases (MAPKs). Because the MAPK family of signalling molecules (phospho-p38 MAPK, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK)) play essential roles in cell signalling pathways that regulate cell growth and inflammation, controlling MAPK mediated pathways is a therapeutically attractive strategy. While small molecule MAPK inhibitors have utility, in this review we will focus on exploring the potential of targeting the endogenous MAPK deactivator--MKP-1. Importantly, there is a strong justification for developing both inhibitors and upregulators of MKP 1 because of the diverse roles played by MAPKs in disease: for example, in cancer, MKP-1 inhibitors may prove beneficial, as MKP-1 is overexpressed and is considered responsible for the failure of JNK-driven apoptotic pathways induced by chemotherapeutics; conversely, in inflammatory diseases such as asthma and arthritis, MKP-1 reduces MAPK-mediated signalling and developing novel ligands to upregulate MKP-1 levels would be a therapeutically attractive anti-inflammatory strategy. Thus, in this review we utilise MKP-1 homology modeling to highlight the structural features of MKP-1 inhibitors that permit potent and selective inhibition, and to provide insights into the structural requirements for selective MKP-1 upregulators. PMID- 22320296 TI - Recent progresses on AI-2 bacterial quorum sensing inhibitors. AB - Quorum sensing (QS) is a communication procedure that predominates gene expression in response to cell density and fluctuations in the neighboring environment as a result of discerning molecules termed autoinducers (AIs). It has been embroiled that QS can govern bacterial behaviors such as the secretion of virulence factors, biofilm formation, bioluminescence production, conjugation, sporulation and swarming motility. Autoinducer 2 (AI-2), a QS signaling molecule brought up to be involved in interspecies communication, exists in both gram negative and -positive bacteria. Therefore, novel approaches to interrupt AI-2 quorum sensing are being recognized as next generation antimicrobials. In the present review article, we summarized recent progresses on AI-2 bacterial quorum sensing inhibitors and discussed their potential as the antibacterial agents. PMID- 22320297 TI - Non-invasive biomarkers of lung inflammation in smoking subjects. AB - Cigarette smoking is the most important risk factor for the development of chronic obstructive pulmonary disease (COPD) and lung cancer, but only a part of smoking subjects develop these respiratory pathologies. Therefore, it is necessary to find sensible parameters to detect early lung alterations due to chronic tobacco smoke exposure. Long-term cigarette smoking is associated with a persistent inflammatory response in the lung that leads to tissue injury and dysfunction. Bronchoscopy and bronchial biopsies are the gold standard techniques for assessing pulmonary inflammation, but are invasive and not routinely used. Cellular analysis of induced sputum and measurement of fraction of exhaled nitric oxide (F(E)NO) are validated non-invasive techniques for assessing respiratory inflammation. Measurement of biomolecules in sputum supernatants and exhaled breath condensate (EBC) are used as a research tool, but require standardization of procedures and, generally, analytical validation. Electronic nose differentiates healthy smokers from healthy nonsmokers based on breath volatile organic compounds (VOC) patterns. These techniques are potentially useful for identifying biomarkers of pulmonary inflammation and oxidative stress. Induced sputum, F(E)NO, EBC and electronic nose are suitable for longitudinal sampling, thereby facilitating monitoring of lung damage process. This approach could enable an early identification of subgroups of healthy smokers at higher risk for tobacco-induced lung damage and prompt planning of secondary prevention strategies. PMID- 22320298 TI - Nonviral approach for targeted nucleic acid delivery. AB - Despite their relatively lower efficiency, nonviral approaches are emerging as safer alternatives in gene therapy to viral vectors. Delivery of nucleic acids to the target site is an important factor for effective gene expression (plasmid DNA) or knockdown (siRNA) with minimal side effects. Direct deposition at the target site by physical methods, including ultrasound, electroporation and gene gun, is one approach for local delivery. For less accessible sites, the development of carriers that can home into the target tissue is required. Cationic peptides, lipoplexes, polyplexes and nanoplexes have been used as carriers for delivery of nucleic acids. Targeting ligands, such as cell targeting peptides, have also been applied to decorate delivery vehicles in order to enhance their efficacy. This review focuses on delivery strategies and recent progress in non-viral carriers and their modifications to improve their performance in targeting and transfection. PMID- 22320299 TI - Exploring pharmacological significance of chalcone scaffold: a review. AB - Chalcones (1,3-diaryl-2-propen-1-ones) and their heterocyclic analogues, belong to the flavonoid family, which possess a number of interesting biological properties such as antioxidant, cytotoxic, anticancer, antimicrobial, antiprotozoal, antiulcer, antihistaminic and anti-inflammatory activities. Several pure chalcones have been approved for clinical use or tested in humans. Clinical trials have shown that these compounds reached reasonable plasma concentration and are well-tolerated. For this reason they are an object of continuously growing interest amongst the scientists. However, much of the pharmacological potential of chalcones is still not utilized. The purpose of this review is to provide an overview of the pharmacological activity of naturally occurring and synthetic chalcones. This review highlights more recent pharmacological screening of these compounds, their mechanisms of action and relevant structure-activity relationships. PMID- 22320300 TI - Specific noncovalent interactions at protein-ligand interface: implications for rational drug design. AB - Specific noncovalent interactions that are indicative of attractive, directional intermolecular forces have always been of key interest to medicinal chemists in their search for the "glue" that holds drugs and their targets together. With the rapid increase in the number of solved biomolecular structures as well as the performance enhancement of computer hardware and software in recent years, it is now possible to give more comprehensive insight into the geometrical characteristics and energetic landscape of certain sophisticated noncovalent interactions present at the binding interface of protein receptors and small ligands based on accumulated knowledge gaining from the combination of two quite disparate but complementary approaches: crystallographic data analysis and quantum-mechanical ab initio calculation. In this perspective, we survey massive body of published works relating to structural characterization and theoretical investigation of three kinds of strong, specific, direct, enthalpy-driven intermolecular forces, including hydrogen bond, halogen bond and salt bridge, involved in the formation of protein-ligand complex architecture in order to characterize their biological functions in conferring affinity and specificity for ligand recognition by host protein. In particular, the biomedical implications of raised knowledge are discussed with respect to potential applications in rational drug design. PMID- 22320301 TI - Recent researches in triazole compounds as medicinal drugs. AB - Triazole compounds containing three nitrogen atoms in the five-membered aromatic azole ring are readily able to bind with a variety of enzymes and receptors in biological system via diverse non-covalent interactions, and thus display versatile biological activities. The related researches in triazole-based derivatives as medicinal drugs have been an extremely active topic, and numerous excellent achievements have been acquired. Noticeably, a large number of triazole compounds as clinical drugs or candidates have been frequently employed for the treatment of various types of diseases, which have shown their large development value and wide potential as medicinal agents. This work systematically reviewed the recent researches and developments of the whole range of triazole compounds as medicinal drugs, including antifungal, anticancer, antibacterial, antitubercular, antiviral, anti-inflammatory and analgesic, anticonvulsant, antiparasitic, antidiabetic, anti-obesitic, antihistaminic, anti-neuropathic, antihypertensive as well as other biological activities. The perspectives of the foreseeable future in the research and development of triazole-based compounds as medicinal drugs are also presented. It is hoped that this review will serve as a stimulant for new thoughts in the quest for rational designs of more active and less toxic triazole medicinal drugs. PMID- 22320302 TI - Gyroxin and its biological activity: effects on CNS basement membranes and endothelium and protease-activated receptors. AB - Gyroxin is a glycoprotein isolated from rattlesnake venom, with known thrombin like serine protease properties and behavioral action in the CNS. The mechanism of the latter has eluded experimenters for three decades. In this paper about the in vitro chick retina we demonstrate an excitotoxic CNS action of Gyroxin by observing retinal Intrinsic Optical Signals (IOS). These show sudden dynamic changes in the intact tissue due to gyroxin action. The very fast kinetics of this response precludes deep tissue penetration by the protein, a mechanism of tissue response described here for the first time. At nanomolar concentrations, Gyroxin alters profoundly the optical profiles of retinal spreading depression waves (RSDs), suggesting modulation of ionic transport and metabolism. This effect is reversible in contrast with the acute cell lysis induced with gyroxin pulses at higher concentration. Because there may be more than one target of Gyroxine at the retinal inner limiting membrane, additional biochemical assays were performed to study a possible Na/K-ATPase blockade and PAR receptor activation. We conclude that the Gyroxin interaction with basement membranes of CNS and endothelium triggers conformational phase transitions at basement membranes, with multiple functional consequences. PMID- 22320303 TI - Neuroprotective properties of nicotine. AB - Utilizing the intrinsic optical signal (IOS) of retinal Spreading Depression (rSD) waves and the concomitant transparency changes of the tissue, we show that nicotine, in an in vivo near tissue preparation, has neuroprotective effects against the excitotoxic cell death, mediated through the activation of glutamate receptors. For this study the retinal tissue was treated with NMDA, an agonist for the NMDA-glutamate-receptor, being excitotoxic at higher concentrations, to induce tissue damage. The protective effects of nicotine against glutamate induced neurotoxicity are demonstrated, comparing the IOS with NMDA and NMDA + nicotine. We additionally present data about the decrease of the propagation velocity of rSD waves after nicotine application and show analogical effects obtained with epibatidine, a specific nicotinic acetylcholine receptor (nAChR) agonist. PMID- 22320304 TI - The pharmacological control of neuronal excitability in the retinal spreading depression model of migraine. AB - Spreading Depression is the underlying patho physiological mechanism for the neurological symptoms of migraine aura and is thought to play a major role in triggering migraine. Therefore it seems reasonable to use the Spreading Depression as a pharmacological tool for anti migraine drugs. Drugs that are able to alter parameters of Spreading Depression should also influence appearance and course of migraine attacks. Concerning the classification on the different mechanisms of drug action, especially the retinal Spreading Depression is useful, due to the separation of vascular and neuronal effects. In this study we investigated substances from different classes of common anti migraine drugs on different parameters of the retinal spreading depression. The results are discussed according to the classification of the drug. PMID- 22320305 TI - Intramolecular 1,3-dipolar cycloaddition of nitrile N-oxide accompanied by dearomatization. AB - Intramolecular 1,3-dipolar cycloaddition of 2-phenoxybenzonitrile N-oxides to benzene rings, accompanied by dearomatization, formed the corresponding isoxazolines in high yields. The X-ray single-crystal structure analysis revealed that the reaction formed the cis-adduct as a single isomer. The substituents on the benzene rings markedly affected the reaction rate, yield, and structure of the final product. PMID- 22320306 TI - From a marine neuropeptide to antimicrobial pseudopeptides containing aza-beta(3) amino acids: structure and activity. AB - Incorporation of aza-beta(3)-amino acids into an endogenous neuropeptide from mollusks (ALSGDAFLRF-NH(2)) with weak antimicrobial activity allows the design of new AMPs sequences. Depending on the nature of the substitution, this can render the pseudopeptides inactive or lead to a drastic enhancement of the antimicrobial activity without high cytotoxicity. Structural studies of the pseudopeptides carried out by NMR and circular dichroism show the impact of aza-beta(3)-amino acids on peptide structure. The first three-dimensional structures of pseudopeptides containing aza-beta(3)-amino acids in aqueous micellar SDS were determined and demonstrate that the hydrazino turn can be formed in aqueous solution. Thus, AMP activity can be modulated through structural modifications induced by the nature and the position of such amino acid analogues in the peptide sequences. PMID- 22320307 TI - Disentangling picosecond events that complicate the quantitative use of the calcium sensor YC3.60. AB - Yellow Cameleon 3.60 (YC3.60) is a calcium sensor based on Forster resonance energy transfer (FRET). This sensor is composed of a calmodulin domain and a M13 peptide, which are located in between enhanced cyan-fluorescent protein (ECFP) and the Venus variant of enhanced yellow-fluorescent protein (EYFP). Depending on the calcium concentration, the efficiency of FRET from donor ECFP to acceptor EYFP is changing. In this study, we have recorded time-resolved fluorescence spectra of ECFP, EYFP, and YC3.60 in aqueous solution with picosecond time resolution, using different excitation wavelengths. Detailed insight in the FRET kinetics was obtained by using global and target analyses of time- and wavelength resolved fluorescence of purified YC3.60 in calcium-free and calcium-bound conformations. The results clearly demonstrate that for both conformations, there are two distinct donor populations: a major one giving rise to FRET and a minor one not able to perform FRET. The transfer time for the calcium-bound conformation is 21 ps, whereas it is in the order of 1 ns for the calcium-free conformation. Ratio imaging of acceptor and donor fluorescence intensities of YC3.60 is usually applied to measure Ca(2+) concentrations in living cells. From the obtained results, it is clear that the intensity ratio is strongly influenced by the presence of donor molecules that do not take part in FRET, thereby significantly affecting the quantitative interpretation of the results. PMID- 22320308 TI - Thermodynamics of protein self-association and unfolding. The case of apolipoprotein A-I. AB - Protein self-association and protein unfolding are two temperature-dependent processes whose understanding is of utmost importance for the development of biological pharmaceuticals because protein association may stabilize or destabilize protein structure and function. Here we present new theoretical and experimental methods for analyzing the thermodynamics of self-association and unfolding. We used isothermal dilution calorimetry and analytical ultracentrifugation to measure protein self-association and introduced binding partition functions to analyze the cooperative association equilibria. In a second type of experiment, we monitored thermal protein unfolding with differential scanning calorimetry and circular dichroism spectroscopy and used the Zimm-Bragg theory to analyze the unfolding process. For alpha-helical proteins, the cooperative Zimm-Bragg theory appears to be a powerful alternative to the classical two-state model. As a model protein, we chose highly purified human recombinant apolipoprotein A-I. Self-association of Apo A-I showed a maximum at 21 degrees C with an association constant Ka of 5.6 * 10(5) M(-1), a cooperativity parameter sigma of 0.003, and a maximal association number n of 8. The association enthalpy was linearly dependent on temperature and changed from endothermic at low temperatures to exothermic above 21 degrees C with a molar heat capacity DeltaC(p) degrees of -2.76 kJ mol(-1) K(-1). Above 45 degrees C, the association could no longer be measured because of the onset of unfolding. Unfolding occurred between 45 and 65 degrees C and was reversible and independent of protein concentration up to 160 MUM. The midpoint of unfolding (T(0)) as measured by DSC was 52-53 degrees C; the enthalpy of unfolding (DeltaH(N)(U)) was 420 kJ/mol. The molar heat capacity (Delta(N)(U)C(p)) increased by 5.0 +/- 0.5 kJ mol(-1) K(-1) upon unfolding corresponding to a loss of 80-85 helical segments, which was confirmed by circular dichroism spectroscopy. Unfolding was highly cooperative with a nucleation parameter sigma of 4.4 * 10(-5). PMID- 22320309 TI - Cyclo- and carbophosphazene-supported ligands for the assembly of heterometallic (Cu2+/Ca2+, Cu2+/Dy3+, Cu2+/Tb3+) complexes: synthesis, structure, and magnetism. AB - The carbophosphazene and cyclophosphazene hydrazides, [{NC(N(CH(3))(2))}(2){NP{N(CH(3))NH(2)}(2)}] (1) and [N(3)P(3)(O(2)C(12)H(8))(2){N(CH(3))NH(2)}(2)] were condensed with o-vanillin to afford the multisite coordination ligands [{NC(N(CH(3))(2))}(2){NP{N(CH(3))N?CH C(6)H(3)-(o-OH)(m-OCH(3))}(2)}] (2) and [{N(2)P(2)(O(2)C(12)H(8))(2)}{NP{N(CH(3))N?CH-C (6)H(3)-(o-OH)(m-OCH(3))}(2)}] (3), respectively. These ligands were used for the preparation of heterometallic complexes [{NC(N(CH(3))(2))}(2){NP{N(CH(3))N?CH-C(6)H(3)-(o-O)(m OCH(3))}(2)}{CuCa(NO(3))(2)}] (4), [{NC(N(CH(3))(2))}(2){NP{N(CH(3))N?CH-C(6)H(3) (o-O)(m-OCH(3))}(2)}{Cu(2)Ca(2)(NO(3))(4)}].4H(2)O (5), [{NC(N(CH(3))(2))}(2){NP{N(CH(3))N?CH-C(6)H(3)-(o-O)(m OCH(3))}(2)}{CuDy(NO(3))(4)}].CH(3)COCH(3) (6), [{NP(O(2)C(12)H(8))}(2){NP{N(CH(3))N?CH-C(6)H(3)-(o-O)(m OCH(3))}(2)}{CuDy(NO(3))(3)}] (7), and [{NP(O(2)C(12)H(8))}(2){NP{N(CH(3))N?CH C(6)H(3)-(o-O)(m-OCH(3))}(2)}{CuTb(NO(3))(3)}] (8). The molecular structures of these compounds reveals that the ligands 2 and 3 possess dual coordination pockets which are used to specifically bind the transition metal ion and the alkaline earth/lanthanide metal ion; the Cu(2+)/Ca(2+), Cu(2+)/Tb(3+), and Cu(2+)/Dy(3+) pairs in these compounds are brought together by phenoxide and methoxy oxygen atoms. While 4, 6, 7, and 8 are dinuclear complexes, 5 is a tetranuclear complex. Detailed magnetic properties on 6-8 reveal that these compounds show weak couplings between the magnetic centers and magnetic anisotropy. However, the ac susceptibility experiments did not reveal any out of phase signal suggesting that in these compounds slow relaxation of magnetization is absent above 1.8 K. PMID- 22320310 TI - Caring for a daughter with intellectual disabilities in managing menstruation: a mother's perspective. AB - BACKGROUND: The concerns of mothers and their experiences while providing help to their daughters with intellectual disability (ID) and considerable support needs during menstruation have rarely been addressed. This qualitative study explored mothers' experiences and perceptions of managing their daughters' menstruation. METHOD: Twelve Taiwanese mothers of 13 daughters with ID (1 mother had twins) were interviewed to explore their experiences of providing help to their daughters with high support needs during menstruation. RESULTS: Support networks were limited and mothers developed their own strategies for managing their daughter's menstruation. Surgical hysterectomy or use of medication to cease or postpone menstrual bleeding was never considered by the mothers. The financial cost of menstrual pads and nappies was significant. CONCLUSIONS: Both an appropriate allowance for families involved in the menstrual care of women with ID and access to appropriate support are needed. More information and educational programs need to be provided to relevant professionals and carers. PMID- 22320311 TI - Surface shear rheology of adsorption layers from the protein HFBII hydrophobin: effect of added beta-casein. AB - The surface shear rheology of hydrophobin HFBII adsorption layers is studied in angle-ramp/relaxation regime by means of a rotational rheometer. The behavior of the system is investigated at different shear rates and concentrations of added beta-casein. In angle-ramp regime, the experimental data comply with the Maxwell model of viscoelastic behavior. From the fits of the rheological curves with this model, the surface shear elasticity and viscosity, E(sh) and eta(sh), are determined at various fixed shear rates. The dependence of eta(sh) on the rate of strain obeys the Herschel-Bulkley law. The data indicate an increasing fluidization (softening) of the layers with the rise of the shear rate. The addition of beta-casein leads to more rigid adsorption layers, which exhibit a tendency of faster fluidization at increasing shear rates. In relaxation regime, the system obeys a modified Andrade's (cubic root) law, with two characteristic relaxation times. The fact that the data comply with the Maxwell model in angle ramp regime, but follow the modified Andrade's low in relaxation regime, can be explained by the different processes occurring in the viscoelastic protein adsorption layer in these two regimes: breakage and restoration of intermolecular bonds at angle-ramp vs solidification of the layer at relaxation. PMID- 22320312 TI - Chiral metabonomics: 1H NMR-based enantiospecific differentiation of metabolites in human urine via direct cosolvation with beta-cyclodextrin. AB - Differences in molecular chirality remain an important issue in drug metabolism and pharmacokinetics for the pharmaceutical industry and regulatory authorities, and chirality is an important feature of many endogenous metabolites. We present a method for the rapid, direct differentiation and identification of chiral drug enantiomers in human urine without pretreatment of any kind. Using the well-known anti-inflammatory chemical ibuprofen as one example, we demonstrate that the enantiomers of ibuprofen and the diastereoisomers of one of its main metabolites, the glucuronidated carboxylate derivative, can be resolved by (1)H NMR spectroscopy as a consequence of direct addition of the chiral cosolvating agent (CSA) beta-cyclodextrin (betaCD). This approach is simple, rapid, and robust, involves minimal sample manipulation, and does not require derivatization or purification of the sample. In addition, the method should allow the enantiodifferentiation of endogenous chiral metabolites, and this has potential value for differentiating metabolites from mammalian and microbial sources in biofluids. From these initial findings, we propose that more extensive and detailed enantiospecific metabolic profiling could be possible using CSA-NMR spectroscopy than has been previously reported. PMID- 22320313 TI - Towards the identification of blood biomarkers for acute stroke in humans: a comprehensive systematic review. AB - AIMS: Identification of biomarkers for stroke will aid our understanding of its aetiology, provide diagnostic and prognostic indicators for patient selection and stratification, and play a significant role in developing personalized medicine. We undertook the largest systematic review conducted to date in an attempt to characterize diagnostic and prognostic biomarkers in acute ischaemic and haemorrhagic stroke and those likely to predict complications following thrombolysis. METHODS: A comprehensive literature search was carried out to identify diagnostic and prognostic stroke blood biomarkers. Mean differences (MDs) and 95% confidence intervals (CIs) were calculated for each biomarker. RESULTS: We identified a total of 141 relevant studies, interrogating 136 different biomarkers. Three biomarkers (C-reactive protein, P-selectin and homocysteine) significantly differentiated between ischaemic stroke and healthy control subjects. Furthermore, glial fibrillary acidic protein levels were significantly different between haemorrhagic stroke and ischaemic stroke patients (MD 224.58 ng l-1; 95% CI 25.84, 423.32; P= 0.03), high levels of admission glucose were a strong predictor of poor prognosis after ischaemic stroke and symptomatic intracerebral haemorrhage post-thrombolysis, glutamate was found to be an indicator of progressive (unstable) stroke (MD 172.65 umol l-1, 95% CI 130.54, 214.75; P= 0.00001), D-dimer predicted in-hospital death (MD 0.67 ug ml 1, 95% CI 0.35, 1.00; P= 0.0001), and high fibrinogen levels were associated with poor outcome at 3 months (MD 47.90 mg l-1, 95% CI 14.88, 80.93; P= 0.004) following ischaemic stroke. CONCLUSIONS: Few biomarkers currently investigated have meaningful clinical value. Admission glucose may be a strong marker of poor prognosis following acute thrombolytic treatment. However, molecules released in the bloodstream before, during or after stroke may have potential to be translated into sensitive blood-based tests. PMID- 22320314 TI - Stability of voxel values from cone-beam computed tomography for dental use in evaluating bone mineral content. AB - OBJECTIVES: The objective of this study was to investigate the stability of voxel values from cone-beam CT (CBCT) using a flat panel detector in changing surrounding circumstances mimicking clinical situations. MATERIALS AND METHODS: Seven hydroxyapatite (HA) rods (0, 40, 80, 120, 160, 199, and 239 mg Ca/cm(3) ) were set in a 16 cm diameter water phantom and scanned with CBCT (FineCube) and also with multislice CT (MSCT) used as reference. The voxel values from CBCT were measured by the obtained images with OsiriX software (http://www.osirix viewer.com), and compared with the CT numbers from MSCT. We examined the correlation between the voxel values and the HA contents, the variance of voxel values, and the influence of changing surrounding circumstances on the voxel values. RESULTS: The voxel values from CBCT were different from the CT numbers from MSCT, but there was a linear Pearson correlation between the voxel values and the HA contents. The voxel values were greatly influenced when the samples were scanned surrounded in air. However, the voxel values were not affected significantly in the existence of materials simulating oral hard tissues and/or a metal core post. CONCLUSIONS: There was a linear correlation between the voxel values of CBCT and the contents of HA rod samples. Our study indicated that it might be possible to evaluate bone mineral content(BMC) from the voxel values of CBCT for dental implant treatment. PMID- 22320315 TI - Downregulated Dicer expression predicts poor prognosis in chronic lymphocytic leukemia. AB - Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world. Alterations in microRNAs (miRNAs) expression have been proposed to play a role in CLL pathogenesis. Dicer and Drosha are the main regulators of miRNA biogenesis, and deregulation of their expression has been indicated as a possible cause of miRNA alterations observed in various cancers. To investigate the role of Dicer and Drosha in CLL, we assessed the expression of Dicer and Drosha and their correlation with other prognostic factors, including Binet stages, immunoglobulin heavy chain variable gene (IGHV) mutation status, TP53 mutation status, ZAP-70 protein and CD38 expression level in 165 CLL patients by using real-time polymerase chain reaction methods. Patients with unmutated IGHV genes had significantly lower expression of Dicer than patients with IGHV mutations. The lower expression level of Dicer was also significantly associated with higher level of CD38 and ZAP-70, and more aggressive Binet stage. We also analyzed Dicer expression in different cytogenetic subgroups. Lower Dicer level was found in patients with unfavorable cytogenetic aberrations (deletion in 17p13 or 11q22.3) in contrast to higher level in good risk cytogenetics (deletion in 13q14 as the sole abnormality). Furthermore, the lower expression of Dicer in CLL shows a strong association with shorter overall survival (OS) (P = 0.0046) as well as with reduced treatment free survival (TFS) (P = 0.0006). By contrast, no differences in the expression of Drosha among these groups of patients were observed. Our data suggest that Dicer expression may play an important role in the progression and prognosis of CLL. PMID- 22320316 TI - Age-specific incidence rates for breast cancer in carriers of BRCA1 mutations from Norway. AB - Incidence rates of breast cancer among women with a BRCA1 mutation vary according to their reproductive histories and country of residence. To measure cancer incidence, it is best to follow-up cohort of healthy women prospectively. We followed up a cohort of 675 women with a BRCA1 mutation who did not have breast or ovarian cancer before inclusion and who had a normal clinical examination and mammography at first visit. After a mean of 7.1 years, 98 incident cases of breast cancer were recorded in the cohort. Annual cancer incidence rates were calculated, and based on these, a penetrance curve was constructed. The average annual cancer risk for the Norwegian women from age 25 to 70 was 2.0%. Founder mutations had lower incidence rate (1.7%) than less frequent mutations (2.5%) (p = 0.03). The peak incidence (3.1% annual risk) was observed in women from age 50 to 59. The age-specific annual incidence rates and penetrance estimate were compared with published figures for women from North America and from Poland. The risk of breast cancer to age 70 was estimated to be 61% for women from Norway, compared with 55% for women from Poland and 69% for women from North America. PMID- 22320324 TI - Activities of topoisomerase I in its complex with SRSF1. AB - Human DNA topoisomerase I (topo I) catalyzes DNA relaxation and phosphorylates SRSF1. Whereas the structure of topo I complexed with DNA has been resolved, the structure of topo I in the complex with SRSF1 and structural determinants of topo I activities in this complex are not known. The main obstacle to resolving the structure is a contribution of unfolded domains of topo I and SRSF1 in formation of the complex. To overcome this difficulty, we employed a three-step strategy: identifying the interaction regions, modeling the complex, and validating the model with biochemical methods. The binding sites in both topo I and SRSF1 are localized in the structured regions as well as in the unfolded domains. One observes cooperation between the binding sites in topo I but not in SRSF1. Our results indicate two features of the unfolded RS domain of SRSF1 containing phosphorylated residues that are critical for the kinase activity of topo I: its spatial arrangement relative to topo I and the organization of its sequence. The efficiency of phosphorylation of SRSF1 depends on the length and flexibility of the spacer between the two RRM domains that uniquely determine an arrangement of the RS domain relative to topo I. The spacer also influences inhibition of DNA nicking, a prerequisite for DNA relaxation. To be phosphorylated, the RS domain has to include a short sequence recognized by topo I. A lack of this sequence in the mutants of SRSF1 or its spatial inaccessibility in SRSF9 makes them inadequate as topo I/kinase substrates. PMID- 22320325 TI - Overexpression of the DNA sensor proteins, absent in melanoma 2 and interferon inducible 16, contributes to tumorigenesis of oral squamous cell carcinoma with p53 inactivation. AB - The development of oral squamous cell carcinoma (OSCC) is a multistep process that requires the accumulation of genetic alterations. To identify genes responsible for OSCC development, we performed high-density single nucleotide polymorphism array analysis and genome-wide gene expression profiling on OSCC tumors. These analyses indicated that the absent in melanoma 2 (AIM2) gene and the interferon-inducible gene 16 (IFI16) mapped to the hematopoietic interferon inducible nuclear proteins. The 200-amino-acid repeat gene cluster in the amplified region of chromosome 1q23 is overexpressed in OSCC. Both AIM2 and IFI16 are cytoplasmic double-stranded DNA sensors for innate immunity and act as tumor suppressors in several human cancers. Knockdown of AIM2 or IFI16 in OSCC cells results in the suppression of cell growth and apoptosis, accompanied by the downregulation of nuclear factor kappa-light-chain-enhancer of activated B cells activation. Because all OSCC cell lines have reduced p53 activity, wild-type p53 was introduced in p53-deficient OSCC cells. The expression of wild-type p53 suppressed cell growth and induced apoptosis via suppression of nuclear factor kappa-light-chain-enhancer of activated B cells activity. Finally, the co expression of AIM2 and IFI16 significantly enhanced cell growth in p53-deficient cells; in contrast, the expression of AIM2 and/or IFI16 in cells bearing wild type p53 suppressed cell growth. Moreover, AIM2 and IFI16 synergistically enhanced nuclear factor kappa-light-chain-enhancer of activated B cells signaling in p53-deficient cells. Thus, expression of AIM2 and IFI16 may have oncogenic activities in the OSCC cells that have inactivated the p53 system. PMID- 22320326 TI - Double pulmonary vein response to a single atrial stimulation. PMID- 22320327 TI - Structure-based design of novel class II c-Met inhibitors: 2. SAR and kinase selectivity profiles of the pyrazolone series. AB - As part of our effort toward developing an effective therapeutic agent for c-Met dependent tumors, a pyrazolone-based class II c-Met inhibitor, N-(4-((6,7 dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3 dihydro-1H-pyrazole-4-carboxamide (1), was identified. Knowledge of the binding mode of this molecule in both c-Met and VEGFR-2 proteins led to a novel strategy for designing more selective analogues of 1. Along with detailed SAR information, we demonstrate that the low kinase selectivity associated with class II c-Met inhibitors can be improved significantly. This work resulted in the discovery of potent c-Met inhibitors with improved selectivity profiles over VEGFR-2 and IGF 1R that could serve as useful tools to probe the relationship between kinase selectivity and in vivo efficacy in tumor xenograft models. Compound 59e (AMG 458) was ultimately advanced into preclinical safety studies. PMID- 22320328 TI - Conformational distribution of trans-stilbene in solution investigated by liquid crystal NMR spectroscopy and compared with in vacuo theoretical predictions. AB - The basic question about the structure and the conformational distribution of a pi-conjugated, flexible organic molecule (interesting in itself, in relation to the balance of forces determining its torsional equilibrium) becomes a really intriguing problem in the case of trans-stilbene (t-St), a "fundamental" molecule from a chemical point of view, as well as the prototype fragment of a series of derivatives endowed with several important biological and technological properties. As a matter of fact, the problem of t-St planarity when the molecule is isolated or in solution is a particularly debated question. In the present paper we studied the conformational distribution of t-St in solution, by resorting to the powerful technique of liquid crystal NMR spectroscopy (LXNMR), and we compared the obtained experimental results with accurate theoretical calculations carried out in vacuo, by using the MP2/6-31G** method (allowing for bond lengths and angles relaxation every 3 degrees torsional steps). Our theoretical and experimental outcomes agree in indicating the nonplanarity of the molecule which, on the contrary, exhibits the coexistence of four stable rotamers, two by two symmetry related. In particular, we have found a couple of global minima corresponding to propeller-like C(2) symmetry conformations, where both the rings are "disrotated", with respect to the vinyl group, of about 17 degrees in solution and of 27 degrees in vacuo (theoretical value). Besides this, the presence of a couple of C(i) local minima, with both the rings "conrotated" of 17 degrees (fluid phase) or of 27 degrees (MP2/6-31G** calculations for the isolated molecule) has been determined. PMID- 22320329 TI - In situ optical microspectroscopy monitoring of binary colloidal crystal growth dynamics via evaporation-induced cooperative self-assembly. AB - Real-time monitoring of the binary colloidal crystal (bCC) growth via evaporation induced cooperative self-assembly (EICSA) was studied by an in situ optical microspectroscopy technique. Evolution of the recorded reflectance spectra reveals that the whole growth process of bCCs via EICSA could be separated into three different stages corresponding to that of unary colloidal crystals because of the same evaporation model. We show the detailed cooperative self-assembly information, including the evolution of the number of layers and filling factors of different components of the growing bCCs using the scalar wave approximation method. Furthermore, when the size ratio and number ratio of the two colloids were varied, the real-time optical properties of the bCCs with various stoichiometric configurations were investigated systematically. This study would be valuable in furthering the current understanding of the bCC growth dynamics via EICSA and tailoring optical properties of hierarchical materials for applications in many fields. PMID- 22320330 TI - Top-down FTICR MS for the identification of fluorescent labeling efficiency and specificity of the Cu-protein azurin. AB - Fluorescent protein labeling has been an indispensable tool in many applications of biochemical, biophysical, and cell biological research. Although detailed information about the labeling stoichiometry and exact location of the label is often not necessary, for other purposes, this information is crucial. We have studied the potential of top-down electrospray ionization (ESI)-15T Fourier transform ion cyclotron resonance (FTICR) mass spectrometry to study the degree and positioning of fluorescent labeling. For this purpose, we have labeled the Cu protein azurin with the fluorescent label ATTO 655-N-hydroxysuccinimide(NHS) ester and fractionated the sample using anion exchange chromatography. Subsequently, individual fractions were analyzed by ESI-15T FTICR to determine the labeling stoichiometry, followed by top-down MS fragmentation, to locate the position of the label. Results showed that, upon labeling with ATTO 655-NHS, multiple different species of either singly or doubly labeled azurin were formed. Top-down fragmentation of different species, either with or without the copper, resulted in a sequence coverage of approximately 50%. Different primary amine groups were found to be (potential) labeling sites, and Lys-122 was identified as the major labeling attachment site. In conclusion, we have demonstrated that anion exchange chromatography in combination with ultrahigh resolution 15T ESI FTICR top-down mass spectrometry is a valuable tool for measuring fluorescent labeling efficiency and specificity. PMID- 22320331 TI - Deposition of nanometer scaled calcium-phosphate crystals to implants with a dual acid-etched surface does not improve early tissue integration. AB - OBJECTIVE: To evaluate hard and soft tissue healing to implants with a dual acid etched surface with and without deposition of calcium-phosphate crystals. MATERIALS AND METHODS: Three months after extraction of mandibular premolars in six Labrador dogs, four osteotomy preparations, 8 mm deep and 3 mm wide, were performed. The prepared canals were widened in the marginal 4 mm zone to 3.74 mm. Implants with an 8 mm long and 3.75 mm wide intraosseous portion and a 5.0 mm high and 4.0 mm wide transmucosal part were placed in such a way that the base of the wider neck-portion of the implant coincided with the crestal bone. The implants were dual acid - etched (Osseotite((r)); Biomet 3i). The surface of the test implants was, in addition, modified by a discrete deposition of calcium phosphate crystals (NanotiteTM; Biomet 3i). Every second implant placed was a test unit. After 2 weeks the implant installation procedure was repeated in the opposite side of the mandible. Two weeks later the animals were euthanized and biopsies were obtained and prepared for histological analysis. RESULTS: The degree of bone-to implant contact (BIC%) was larger at implants without (Osseotite) than in those with (Nanotite) calcium-phosphate crystals. No differences were found regarding soft tissue dimensions and composition between the two types of implants. CONCLUSION: It is suggested that deposition of nanometer-sized calcium-phosphate crystals to implants with a dual acid-etched surface does not improve early tissue integration. PMID- 22320333 TI - Role of calcium in metalloenzymes: effects of calcium removal on the axial ligation geometry and magnetic properties of the catalytic diheme center in MauG. AB - MauG is a diheme enzyme possessing a five-coordinate high-spin heme with an axial His ligand and a six-coordinate low-spin heme with His-Tyr axial ligation. A Ca(2+) ion is linked to the two hemes via hydrogen bond networks, and the enzyme activity depends on its presence. Removal of Ca(2+) altered the electron paramagnetic resonance (EPR) signals of each ferric heme such that the intensity of the high-spin heme was decreased and the low-spin heme was significantly broadened. Addition of Ca(2+) back to the sample restored the original EPR signals and enzyme activity. The molecular basis for this Ca(2+)-dependent behavior was studied by magnetic resonance and Mossbauer spectroscopy. The results show that in the Ca(2+)-depleted MauG the high-spin heme was converted to a low-spin heme and the original low-spin heme exhibited a change in the relative orientations of its two axial ligands. The properties of these two hemes are each different than those of the heme in native MauG and are now similar to each other. The EPR spectrum of Ca(2+)-free MauG appears to describe one set of low spin ferric heme signals with a large g(max) and g anisotropy and a greatly altered spin relaxation property. Both EPR and Mossbauer spectroscopic results show that the two hemes are present as unusual highly rhombic low-spin hemes in Ca(2+)-depleted MauG, with a smaller orientation angle between the two axial ligand planes. These findings provide insight into the correlation of enzyme activity with the orientation of axial heme ligands and describe a role for the calcium ion in maintaining this structural orientation that is required for activity. PMID- 22320334 TI - Understanding pediatricians' views toward school-based BMI screening in Massachusetts: a pilot study. AB - BACKGROUND: Massachusetts (MA) mandated body mass index (BMI) screening in schools in 2010. However, little is known about pediatricians' views on school based screening or how the pediatricians' perspectives might affect the school based screening process. We assessed MA pediatricians' knowledge, attitudes, beliefs, and practices concerning BMI screening. METHODS: An anonymous Web-based survey was completed by 286 members of the MA Chapter of the American Academy of Pediatrics who provided primary care (40% response rate). RESULTS: Support for school-based BMI screening was mixed. While 16.1% strongly supported it, 12.2% strongly opposed it. About one fifth (20.2%) believed school-based screening would improve communication between schools and pediatricians; 23.0% believed school-based screening would help with patient care. More (32.2%) believed screening in schools would facilitate communication with families. In contrast, pediatricians embraced BMI screening in practice: 91.6% calculated and 85.7% plotted BMI at every well child visit. Pediatricians in urban practices, particularly inner city, had more positive attitudes toward BMI screening in schools, even when adjusting for respondent demographics, practice setting, and proportion of patients in the practice who were overweight/obese (p < .001). CONCLUSION: These data suggest MA pediatricians use BMI screening and support its clinical utility. However, support for school-based BMI screening was mixed. Urban-based pediatricians in this sample held more positive beliefs about screening in schools. Although active collaboration between schools and pediatricians would likely help to ensure that the screenings have a positive impact on child health regardless of location, it may be easier for urban-based schools and pediatricians to be successful in developing partnerships. PMID- 22320335 TI - Promoting the purchase of low-calorie foods from school vending machines: a cluster-randomized controlled study. AB - BACKGROUND: Vending machines account for food sales and revenue in schools. We examined 3 strategies for promoting the sale of lower-calorie food products from vending machines in high schools in the Netherlands. METHODS: A school-based randomized controlled trial was conducted in 13 experimental schools and 15 control schools. Three strategies were tested within each experimental school: increasing the availability of lower-calorie products in vending machines, labeling products, and reducing the price of lower-calorie products. The experimental schools introduced the strategies in 3 consecutive phases, with phase 3 incorporating all 3 strategies. The control schools remained the same. The sales volumes from the vending machines were registered. Products were grouped into (1) extra foods containing empty calories, for example, candies and potato chips, (2) nutrient-rich basic foods, and (3) beverages. They were also divided into favorable, moderately unfavorable, and unfavorable products. RESULTS: Total sales volumes for experimental and control schools did not differ significantly for the extra and beverage products. Proportionally, the higher availability of lower-calorie extra products in the experimental schools led to higher sales of moderately unfavorable extra products than in the control schools, and to higher sales of favorable extra products in experimental schools where students have to stay during breaks. Together, availability, labeling, and price reduction raised the proportional sales of favorable beverages. CONCLUSION: Results indicate that when the availability of lower-calorie foods is increased and is also combined with labeling and reduced prices, students make healthier choices without buying more or fewer products from school vending machines. Changes to school vending machines help to create a healthy school environment. PMID- 22320336 TI - The effect of school dismissal on rates of influenza-like illness in New York City schools during the spring 2009 novel H1N1 outbreak. AB - BACKGROUND: The effects of individual school dismissal on influenza transmission have not been well studied. During the spring 2009 novel H1N1 outbreak, New York City implemented an individual school dismissal policy intended to limit influenza transmission at schools with high rates of influenza-like illness (ILI). METHODS: Active disease surveillance data collected by the New York City Health Department on rates of ILI in schools were used to evaluate the impact. Sixty-four schools that met the Health Department's criteria for considering dismissal were included in the analysis. Twenty-four schools that met criteria subsequently dismissed all classes for approximately 1 school week. A regression model was fit to these data, estimating the effect of school dismissal on rates of in-school ILI following reconvening, adjusting for potential confounders. RESULTS: The model estimated that, on average, school dismissal reduced the rate of ILI by 7.1% over the entire average outbreak period. However, a large proportion of in-school ILI occurred before dismissal criteria were met. A separate model estimated that school absenteeism rates were not significantly affected by dismissal. CONCLUSION: Results suggest that individual school dismissal could be considered in situations where schools have a disproportionate number of high-risk students or may be unable to implement recommended preventive or infection control measures. Future work should focus on developing more sensitive indicators of early outbreak detection in schools and evaluating the impact of school dismissal on community transmission. PMID- 22320337 TI - The prevalence and determinants of tobacco use among adolescents in Saudi Arabia. AB - BACKGROUND: Adolescent tobacco use has been a serious public health issue, resulting in longer duration of tobacco use and higher nicotine dependence in adulthood. This study identified the current status of tobacco use among middle schools students in Jeddah, Saudi Arabia and the factors leading to tobacco use, to provide information on how to effectively prevent tobacco use among adolescents. METHODS: A cross-sectional survey was administered to measure the prevalence of tobacco use and profile tobacco users. School selection was stratified by region, gender, and type (public or private). Altogether, 1186 seventh- to ninth-grade students were selected. Of those, 1019 questionnaires were used for analysis. RESULTS: The mean age of the participants was 14.3 years (SD = 1.2) and boys comprised 54% of the sample. The prevalence of tobacco use among students was 9.72% with a significant difference between sexes (12.43% for boys and 6.65% for girls). Bivariate and multivariate analyses results showed that students whose families had higher income, had larger daily allowances, spent less time studying, skipped class more frequently, were less religious, spent more time out of home, drank more Coca-Cola, intended to use tobacco in the next year, and were males who were more likely to use tobacco. CONCLUSION: Prevention programs designed to reduce adolescent tobacco use need to consider these sociodemographic characteristics. Understanding the characteristics of adolescent tobacco users and the associated sociocultural context is critical for developing effective tobacco prevention programs targeted at adolescents. PMID- 22320338 TI - Comparison of indoor air quality management strategies between the school and district levels in New York State. AB - BACKGROUND: Good school indoor air quality (IAQ) can affect the health and functioning of school occupants. Thus, it is important to assess the degree to which schools and districts employ strategies to ensure good IAQ management. We examined and compared the patterns of IAQ management strategies between public elementary schools and their school districts in New York State. METHODS: District-level information obtained from surveys of district facilities managers in 326 districts was described and stratified by district size and socioeconomic status. School-level information obtained from surveys of head custodians in 770 elementary schools was then compared with the district-level information in 241 districts. RESULTS: About 47% of participating school districts reported having a district-wide IAQ program, with a large range in the prevalence of specific IAQ management strategies. Airing out newly painted areas was the most commonly reported (92%) and having a classroom animal policy was the least commonly reported (29%). Larger districts and districts with a district-wide IAQ program were more likely to report certain IAQ strategies than other districts. Elementary schools and their districts were most likely to report airing out newly painted areas (76%). The most common area of disagreement was construction after hours (50%). The top strategy not reported at either level was having an IAQ coordinator (53%). CONCLUSIONS: Many school districts lack key IAQ management strategies, and differences exist between district-level policy and school-level practice. Districts and schools should work together to formalize and expand existing IAQ policies and inform stakeholders about these strategies. PMID- 22320339 TI - An adaptive community-based participatory approach to formative assessment with high schools for obesity intervention*. AB - BACKGROUND: In the emerging debate around obesity intervention in schools, recent calls have been made for researchers to include local community opinions in the design of interventions. Community-based participatory research (CBPR) is an effective approach for forming community partnerships and integrating local opinions. We used CBPR principles to conduct formative research in identifying acceptable and potentially sustainable obesity intervention strategies in 8 New Mexico school communities. METHODS: We collected formative data from 8 high schools on areas of community interest for school health improvement through collaboration with local School Health Advisory Councils (SHACs) and interviews with students and parents. A survey based on formative results was created to assess acceptability of specific intervention strategies and was provided to SHACs. Quantitative data were analyzed using descriptive statistics while qualitative data were evaluated using an iterative analytic process for thematic identification. RESULTS: Key themes identified through the formative process included lack of healthy food options, infrequent curricular/extracurricular physical activity opportunities, and inadequate exposure to health/nutritional information. Key strategies identified as most acceptable by SHAC members included healthier food options and preparation, a healthy foods marketing campaign, yearly taste tests, an after-school noncompetitive physical activity program, and community linkages to physical activity opportunities. CONCLUSION: An adaptive CBPR approach for formative assessment can be used to identify obesity intervention strategies that address community school health concerns. Eight high school SHACs identified 6 school-based strategies to address parental and student concerns related to obesity. PMID- 22320341 TI - Drug-induced pemphigus after six years of treatment with phenytoin and carbamazepine. PMID- 22320342 TI - Pd-catalyzed dehydrogenative cross-coupling of polyfluoroarenes with heteroatom substituted enones. AB - The first example of intermolecular regioselective alpha-arylation of heteroatom substituted enones with polyfluoroarenes via twofold C-H bond functionalization using a palladium catalyst is reported. This approach provides rapid access to a wide range of alpha-fluoroarylated enones of interest in life science. PMID- 22320343 TI - Structure-based design of novel class II c-Met inhibitors: 1. Identification of pyrazolone-based derivatives. AB - Deregulation of c-Met receptor tyrosine kinase activity leads to tumorigenesis and metastasis in animal models. More importantly, the identification of activating mutations in c-Met, as well as MET gene amplification in human cancers, points to c-Met as an important target for cancer therapy. We have previously described two classes of c-Met kinase inhibitors (class I and class II) that differ in their binding modes and selectivity profiles. The class II inhibitors tend to have activities on multiple kinases. Knowledge of the binding mode of these molecules in the c-Met protein led to the design and evaluation of several new class II c-Met inhibitors that utilize various 5-membered cyclic carboxamides to conformationally restrain key pharmacophoric groups within the molecule. These investigations resulted in the identification of a potent and novel class of pyrazolone c-Met inhibitors with good in vivo activity. PMID- 22320344 TI - Inactivation of ovine cyclooxygenase-1 by bromoaspirin and aspirin: a quantum chemistry description. AB - The resulting noncovalent bonding of the salicylic acid to ovine COX-1 after bromoaspirin and aspirin acetylation by Ser530 is investigated within the scope of density functional theory considering a 6.5 A radius binding pocket. We have not only took full advantage of published X-ray structural data for the ovine COX 1 cocrystallized with bromoaspirin, but we also have improved that data through computation, finding good estimates for the hydrogen atom positions at the residues of the binding pocket, and repositioning the Ser530Ac[Br;H] lateral chain and salicylic acid by total energy minimization procedures employing LDA and GGA+D exchange-correlation functionals. Using bromoaspirin as a template, we have simulated the positioning of aspirin in the binding pocket, estimating its interaction energy with each of its neighbor COX-1 residues. We demonstrate that the binding energies of bromoaspirin and aspirin to COX-1 are very close when second-order quantum refinements of the structural data are performed, which points to an explanation on why the IC(50) values for the 126 MUM COX-1 activity of both bromoaspirin and aspirin are practically the same. Attracting and repelling residues were identified, being shown that Arg120 is the most effective residue attracting the salicylic acid, followed by Ala527, Leu531, Leu359, and Ser353. On the other hand, Glu524 was found the most effective repulsive residue (strength interaction comparable to Arg120). PMID- 22320346 TI - Antitumor effect of berberine against primary effusion lymphoma via inhibition of NF-kappaB pathway. AB - Primary effusion lymphoma (PEL) is an infrequent and distinct entity among the aggressive non-Hodgkin B cell lymphomas that occurs predominantly in patients with advanced AIDS. It shows serous lymphomatous effusion in body cavities, and is resistant to conventional chemotherapy with a poor prognosis. Thus, the optimal treatment for PEL is not well defined and there is a need for novel agents. PEL has been recognized as the tumor caused by Kaposi sarcoma-associated herpes virus/human herpes virus-8 (KSHV/HHV-8), and nuclear factor (NF)-kappaB activation plays a critical role in the survival and growth of PEL cells. In this study, we assessed the antitumor effect of berberine, a naturally occurring isoquinoline alkaloid, on this pathway. The methylthiotetrazole assay showed that cell proliferation in the PEL cell lines was inhibited by berberine. Berberine also induced caspase-dependent apoptosis and suppressed NF-kappaB activity by inhibiting IkappaB kinase (IKK) phosphorylation, IkappaB phosphorylation and IkappaB degradation, upstream targets of the NF-kappaB pathway, in PEL cells. In a xenograft mouse model that showed ascites and diffuse organ invasion of PEL cells, treatment with berberine inhibited the growth and invasion of PEL cells significantly compared with untreated mice. These results show that the suppression of NF-kappaB is a molecular target for treating PEL, and berberine is a potential antitumor agent for PEL. PMID- 22320347 TI - CO2 deactivation of supported amines: does the nature of amine matter? AB - Adsorption of CO(2) was investigated on a series of primary, secondary, and tertiary monoamine-grafted pore-expanded mesoporous MCM-41 silicas, referred to as pMONO, sMONO, and tMONO, respectively. The pMONO adsorbent showed the highest CO(2) adsorption capacity, followed by sMONO, whereas tMONO exhibited hardly any CO(2) uptake. As for the stability in the presence of dry CO(2), we showed in a previous contribution [J. Am. Chem. Soc.2010, 132, 6312-6314] that amine supported materials deactivate in the presence of dry CO(2) via the formation of urea linkages. Here, we showed that only primary amines suffered extensive loss in CO(2) uptake, whereas secondary and tertiary amines were stable even at temperature as high as 200 degrees C. The difference in the stability of primary vs secondary and tertiary amines was associated with the occurrence of isocyanate as intermediate species toward the formation of urea groups, since only primary amines can be precursors to isocyanate in the presence of CO(2). However, using a grafted propyldiethylenetriamine containing both primary and secondary amines, we demonstrated that while primary amines gave rise to isocyanate, the latter can react with either primary or secondary amines to generate di- and trisubstituted ureas, leading to deactivation of secondary amines as well. PMID- 22320348 TI - Cardiac resynchronization therapy in an infant with double outlet right ventricle and mechanical dyssynchrony. AB - Cardiac resynchronization therapy (CRT) is commonly used in adults with heart failure, poor left ventricular ejection fraction (LVEF), and wide QRS complex. CRT has rarely been applied in young patients. We report the case of a 10-month old infant with congenital heart disease, postsurgical complete atrioventricular block, and severe refractory heart failure. The patient showed a significant clinical improvement and was withdrawn from the heart transplant list 2 months after epicardially established CRT. PMID- 22320349 TI - Investigation of the haemodynamic effects of exenatide in healthy male subjects. AB - AIMS: In clinical studies of glucagon-like peptide-1 (GLP-1) agonists used in the management of patients with type 2 diabetes, there is often a small accompanying fall in blood pressure. The mechanism underlying this effect is not known, although exenatide, a GLP-1 mimetic, has acute regional vasodilator properties in rats. We have therefore studied the haemodynamic effects of exenatide in healthy male volunteers. METHODS: We compared the effects of a single 10 ug subcutaneous injection of exenatide with placebo in a double-blind, randomized, crossover study. For 2 h after dosing, haemodynamic measurements were made using a Finometer, venous occlusion plethysmography and Doppler ultrasound. The urine sodium : creatinine excretion ratio was determined. RESULTS: At the end of the study when exenatide was compared with placebo, heart rate had risen by a mean of 8.2 (95% CI 4.2, 12.2, P < 0.01) beats min(-1) , cardiac output by a mean of 1.2 (95% CI 0.42, 20.3, P < 0.05) l min(-1) and total peripheral resistance had fallen by 120 (95% CI -8, -233, P < 0.05) dyn s cm(-5) .There were no differences in blood pressure. The urinary sodium : creatinine ratio was increased by mean 12.4 (95% CI 4.6, 20.2, P < 0.05) mmol mmol(-1) when exenatide was compared with placebo. CONCLUSIONS: Exenatide has significant haemodynamic effects in healthy volunteers. The results of this study are consistent with exenatide having both vasodilator and natriuretic properties. The vascular changes may contribute to the hypotensive effect of exenatide when used chronically in patients with diabetes. PMID- 22320351 TI - Two translation products of Yersinia yscQ assemble to form a complex essential to type III secretion. AB - The bacterial flagellar C-ring is composed of two essential proteins, FliM and FliN. The smaller protein, FliN, is similar to the C-terminus of the larger protein, FliM, both being composed of SpoA domains. While bacterial type III secretion (T3S) systems encode many proteins in common with the flagellum, they mostly have a single protein in place of FliM and FliN. This protein resembles FliM at its N-terminus and is as large as FliM but is more like FliN at its C terminal SpoA domain. We have discovered that a FliN-sized cognate indeed exists in the Yersinia T3S system to accompany the FliM-sized cognate. The FliN-sized cognate, YscQ-C, is the product of an internal translation initiation site within the locus encoding the FliM-sized cognate YscQ. Both intact YscQ and YscQ-C were found to be required for T3S, indicating that the internal translation initiation site, which is conserved in some but not all YscQ orthologs, is crucial for function. The crystal structure of YscQ-C revealed a SpoA domain that forms a highly intertwined, domain-swapped homodimer, similar to those observed in FliN and the YscQ ortholog HrcQ(B). A single YscQ-C homodimer associated reversibly with a single molecule of intact YscQ, indicating conformational differences between the SpoA domains of intact YscQ and YscQ-C. A "snap-back" mechanism suggested by the structure can account for this. The 1:2 YscQ-YscQ-C complex is a close mimic of the 1:4 FliM-FliN complex and the likely building block of the putative Yersinia T3S system C-ring. PMID- 22320352 TI - Photocatalytic [2 + 2] cycloadditions of enones with cleavable redox auxiliaries. AB - alpha,beta-Unsaturated 2-imidazolyl ketones undergo [2 + 2] cycloaddition with a variety of Michael acceptors upon irradiation with visible light in the presence of Ru(bpy)(3)(2+). Cleavage of the imidazolyl auxiliary from the cycloadducts affords cyclobutane carboxamides, esters, thioesters, and acids that would not be accessible from direct cycloaddition of the corresponding unsaturated carbonyl compounds. PMID- 22320353 TI - Fungal melanonychia due to Candida albicans. PMID- 22320354 TI - Tubulin binding, protein-bound conformation in solution, and antimitotic cellular profiling of noscapine and its derivatives. AB - Noscapine and its 7-hydroxy and 7-amino derivatives were characterized for their binding to tubulin. A solution NMR structure of these compounds bound to tubulin shows that noscapine and its 7-aniline derivative do not compete for the same binding site nor does its small molecule crystal structure match its tubulin bound conformation. These compounds were also tested for their antiproliferative effects on a panel hepatocellular carcinoma cell lines. PMID- 22320355 TI - The use and abuse of heme in apicomplexan parasites. AB - SIGNIFICANCE: Heme is an essential prosthetic group for most life on Earth. It functions in numerous cellular redox reactions, including in antioxidant defenses and at several stages of the electron transport chain in prokaryotes and eukaryotic mitochondria. Heme also functions as a sensor and transport molecule for gases such as oxygen. Heme is a complex organic molecule and can only be synthesized through a multienzyme pathway from simpler precursors. Most free living organisms synthesize their own heme by a broadly conserved metabolic pathway. Parasites are adept at scavenging molecules from their hosts, and heme is no exception. RECENT ADVANCES: In this review we examine recent advances in understanding heme usage and acquisition in Apicomplexa, a group of parasites that include the causative agents of malaria, toxoplasmosis, and several major parasites of livestock. CRITICAL ISSUES: Heme is critical to the survival of Apicomplexa, although the functions of heme in these organisms remain poorly understood. Some Apicomplexa likely scavenge heme from their host organisms, while others retain the ability to synthesize heme. Surprisingly, some Apicomplexa may be able to both synthesize and scavenge heme. Several Apicomplexa live in intracellular environments that contain high levels of heme. Since heme is toxic at high concentrations, parasites must carefully regulate intracellular heme levels and develop mechanisms to detoxify excess heme. Indeed, drugs interfering with heme detoxification serve as major antimalarials. FUTURE DIRECTIONS: Understanding heme requirements and regulation in apicomplexan parasites promises to reveal multiple targets for much-needed therapeutic intervention against these parasites. PMID- 22320357 TI - Fatal outbreaks in dogs associated with pantropic canine coronavirus in France and Belgium. AB - Infection with pantropic canine coronavirus was detected during outbreaks in France and Belgium. This was concurrent in most cases with canine parvovirus 2c. One outbreak was a deadly acute systemic disease with a single pantropic canine coronavirus infection. This is the first report of a fatality associated with pantropic canine coronavirus alone outside Italy. PMID- 22320358 TI - Biomineralization of superhydrophilic vertically aligned carbon nanotubes. AB - Vertically aligned carbon nanotubes (VACNT) promise a great role for the study of tissue regeneration. In this paper, we introduce a new biomimetic mineralization routine employing superhydrophilic VACNT films as highly stable template materials. The biomineralization was obtained after VACNT soaking in simulated body fluid solution. Detailed structural analysis reveals that the polycrystalline biological apatites formed due to the -COOH terminations attached to VACNT tips after oxygen plasma etching. Our approach not only provides a novel route for nanostructured materials, but also suggests that COOH termination sites can play a significant role in biomimetic mineralization. These new nanocomposites are very promising as nanobiomaterials due to the excellent human osteoblast adhesion. PMID- 22320359 TI - Single unit attachments improve peri-implant soft tissue conditions in mandibular overdentures supported by four implants. AB - AIM: To evaluate the clinical performance as well as patients' and clinicians' satisfaction on two different prosthodontic retention systems for implant overdentures in the mandible. METHODS: In this retrospective study, patients provided with four intraforaminal implants with at least 12 months of follow-up since overdenture delivery were evaluated. A total of 39 patients were treated either with Locator((r)) attachment or with cad-cam milled bar. Clinical parameters such as Peri-implant Probing Depth (PPD), Plaque Index (PI), and Bleeding on Probing (BOP) were evaluated. Patients' and clinicians' perceptions regarding the outcome were assessed on visual analog scales (VAS). RESULTS: The mean follow-up was 13 months in the Locator((r)) group and 18 months in the Bar group and no implants were lost. The Locator group showed better results for PPD, PI, and BOP values. Patients' satisfaction was high in both groups, whereas the clinicians found better hygienic conditions and soft tissue health in the Locator group. CONCLUSIONS: Although the patients' satisfaction was similar in both groups the Locator((r)) system demonstrated better soft tissues scores because hygienic maintenance was more complicated around bars. This may increase the frequency of chronic inflammations around the implants. PMID- 22320360 TI - Restoration of critical-size defects in the rabbit mandible using porous nanohydroxyapatite-polyamide scaffolds. AB - Composite nanohydroxyapatite/polyamide (n-HA/PA) biomaterials have been indicated for bone defect reconstruction, where PA is added to enhance the toughness of n HA. However, a comprehensive understanding of the biological performance of this implant material remains to be determined. In this study, the biological activity of n-HA/PA biomaterials was characterized in vitro by assessing the growth of bone marrow stromal cells (BMSCs), and in an in vivo rabbit model. To evaluate the n-HA/PA performance under different osteogenic conditions in vivo, implants were inserted to critical-size bone defects in the angle and body of the rabbit mandible. To determine the necessity of ectogenic BMSC-n-HA/PA hybrids at different implantation sites, both raw n-HA/PA materials and BMSC-seeded n-HA/PA hybrids were implanted. Bone formation was detected by radiology and histological studies. The results showed that n-HA/PA composites had great bioactivity, demonstrating significant BMSC proliferation, active alkaline phosphatase secretion, and stimulating the expression of osteogenic proteins (bone morphogenetic protein 2 [BMP2], osteoprotegerin [OPG], osteopontin [OPN], collagen type I [Col I], and osteocalcin [OCN]), in comparison to the control (polyethylene). At marrow-rich implantation sites (mandibular body), the amount of new bone formation was significant, but was not enhanced by the presence of BMSCs in the BMSC-n-HA/PA hybrids. However, the BMSC-n-HA/PA hybrids were essential for promoting bone formation in marrow-poor sites (mandibular angle). In conclusion, n-HA/PA biomaterials, which offer the advantage of enhanced mechanical performance over n-HA, exhibit significant bioactivity, including the capacity for bone regeneration at marrow-poor sites when implanted in combination with BMSCs. PMID- 22320362 TI - Incidence of immediate hypersensitivity reaction and serum sickness following administration of Crotalidae polyvalent immune Fab antivenom: a meta-analysis. AB - OBJECTIVES: Crotalidae polyvalent immune Fab (ovine) (FabAV) is commonly used in the treatment of symptomatic North American crotaline snake envenomation. When approved by the U.S. Food and Drug Administration in 2000, the incidences of immediate hypersensitivity reactions and serum sickness were reported as 0.14 and 0.18, respectively. The objective of this meta-analysis was to evaluate the incidence of immediate hypersensitivity reactions and serum sickness reported in studies of patients treated with FabAV therapy after North American crotaline envenomation. METHODS: The authors searched PubMed, Ovid MEDLINE, and EMBASE from January 1, 1997, to September 20, 2010, for English-language medical literature and cross-referenced bibliographies of reviewed articles. The published abstracts of the major toxicology conferences were also searched. All prospective and retrospective cohort studies with patients receiving FabAV therapy for North American crotaline envenomations were eligible for data abstraction. Two content experts reviewed full-text articles and extracted relevant study design and outcome data. Proportions of immediate hypersensitivity and serum sickness for each study were analyzed in a random-effects model to produce an overall estimate of immediate hypersensitivity and serum sickness incidence associated with FabAV administration. RESULTS: The literature search revealed 11 unique studies of patients who received FabAV that contained information on immediate hypersensitivity reactions and serum sickness. The meta analysis produced a combined estimate of the incidence of immediate hypersensitivity of 0.08 (95% confidence interval [CI] = 0.05 to 0.11) and a combined estimate of the incidence of serum sickness of 0.13 (95% CI = 0.07 to 0.21). CONCLUSIONS: In this systematic literature review and meta-analysis, the combined estimates of the incidence of immediate hypersensitivity reactions and serum sickness from FabAV in the treatment of symptomatic North American crotaline envenomations appear to be lower than previously reported, at 0.08 and 0.13, respectively. PMID- 22320363 TI - Emergency department neurologic deterioration in patients with spontaneous intracerebral hemorrhage: incidence, predictors, and prognostic significance. AB - OBJECTIVES: The objective was to explore the incidence, predictors, and prognostic significance of emergency department (ED) neurologic deterioration in patients with spontaneous intracerebral hemorrhage (SICH). METHODS: This was a retrospective cohort study conducted at the ED, neurocritical care unit, and general intensive care unit of a university-affiliated medical center. Consecutive adult SICH patients treated in our ED from January 2002 through December 2009 were included, identified from the registered stroke data bank. These were cross-checked for coding with International Classification of Diseases, Ninth Revision, Clinical Modification 431 and 432.9. Enrolled patients had SICH with elapsed times of <12 hours and Glasgow Coma Scale (GCS) scores >= 13 on arrival. ED neurologic deterioration was defined as having a two-or-more point decrease in consciousness noted in any GCS score assessment between ED presentation and admission. Comparisons of numerical data were performed using an unpaired t-test (parametric data) or Mann-Whitney U-test (nonparametric data). Comparisons of categorical data were done by chi-square tests. Variables with p < 0.1 in univariate analysis were further analyzed using multiple logistic regression. No variable automated or manual selection methods were used. RESULTS: Among the 619 patients with SICH included in the study, 22.6% had ED neurologic deterioration. Independent predictors for ED neurologic deterioration included regular antiplatelet use, ictus to ED arrival time under 3 hours, initial body temperature >= 37.5 degrees C, intraparenchymal hemorrhage associated with intraventricular hemorrhage (IVH), and presence of a midline shift of greater than 2 mm on computed tomography (CT). ED neurologic deterioration was associated with 1-week mortality, 30-day mortality, and poor neurologic outcome on discharge. CONCLUSIONS: Nearly one-quarter of SICH patients with an initial GCS of 13 to 15 had a two points or more deterioration of their GCS while in the ED. ED neurologic deterioration was associated with death and poor neurologic outcomes on discharge. Several risk factors that are available early in the patients' courses appear to be associated with ED neurologic deterioration. By identifying patients at risk for early neurologic decline and intervening early, physicians may be able to improve patient outcomes. PMID- 22320364 TI - Identifying high-risk geographic areas for cardiac arrest using three methods for cluster analysis. AB - OBJECTIVES: The objective was to identify high-risk census tracts, defined as those areas that have both a high incidence of out-of-hospital cardiac arrest (OHCA) and a low prevalence of bystander cardiopulmonary resuscitation (CPR), by using three spatial statistical methods. METHODS: This was a secondary analysis of two prospectively collected registries in the city of Columbus, Ohio. Consecutive adult (>=18 years) OHCA patients, restricted to those of cardiac etiology and treated by emergency medical services (EMS) from April 1, 2004, to April 30, 2009, were studied. Three different spatial analysis methods (Global Empirical Bayes, Local Moran's I, and SaTScan's spatial scan statistic) were used to identify high-risk census tracts. RESULTS: A total of 4,553 arrests in 200 census tracts occurred during the study period, with 1,632 arrests included in the final sample after exclusions for no resuscitation attempt, noncardiac etiology, etc. The overall incidence for OHCA was 0.70 per 1,000 people for the 6 year study period (SD = +/-0.52). Bystander CPR occurred in 20.2% (n = 329), with 10.0% (n = 167) surviving to hospital discharge. Five high-risk census tracts were identified by all three analytic methods. CONCLUSIONS: The five high-risk census tracts identified may be possible sites for high-yield targeted community based interventions to improve CPR training and cardiovascular disease education efforts and ultimately improve survival from OHCA. PMID- 22320365 TI - Lack of sex disparity in cardiovascular testing after coronary computerized tomographic angiography. AB - OBJECTIVES: The authors assessed whether there was a sex disparity in testing of patients after coronary computerized tomographic angiography (CTA) was performed for emergency department (ED) patients with potential acute coronary syndromes (ACS). In theory, once coronary anatomy has been determined, any disparity in subsequent workup should not be the result of differences in presentation. METHODS: This was a prospective cohort study of ED patients who presented with potential ACS and received coronary CTAs at a university hospital. Demographics, history, cardiac risk factors, follow-up testing, and procedures were recorded. Follow-up at 30 days was obtained by structured record review and telephone contact. Patients were stratified by sex and coronary CTA results (max stenosis: none, 1% to 24%, 25% to 49%, 50% to 69%, and >=70%). Main outcome was the relative risk (RR) of a male receiving a stress test or catheterization within 30 days, stratified by categories of percent maximal stenosis. RESULTS: A total of 1,144 patients received coronary CTAs (mean +/- SD age = 47.8 +/- 8.7 years), 55% were female, and 64% were black or African American. Overall, 161 patients received follow-up testing within 30 days, 113 during their index visit. Men were more likely to receive further testing (RR = 1.51; 95% confidence interval [CI] = 1.14 to 1.99) compared to women. However, when stratified by percentage of stenosis, men were not more likely to receive further testing within 30 days after coronary CTA compared to women (RR = 1.14; 95% CI = 0.68 to 1.91). In multivariable modeling for risk of further testing, stenosis remained significant (adjusted relative risk [aRR] = 1.51; 95% CI = 1.19 to 1.91), while male sex, age, race, and Thrombolysis in Myocardial Infarction (TIMI) risk score were not. CONCLUSIONS: Male patients with potential ACS who receive a coronary CTA as a part of their ED evaluation were no more likely than female patients to receive further testing within 30 days. PMID- 22320366 TI - Ground emergency medical services requests for helicopter transfer of ST-segment elevation myocardial infarction patients decrease medical contact to balloon times in rural and suburban settings. AB - OBJECTIVES: ST-segment elevation myocardial infarction (STEMI) care is time dependent. Many STEMI patients require interhospital helicopter transfer for percutaneous coronary intervention (PCI) if ground emergency medical services (EMS) initially transport the patient to a non-PCI center. This investigation models potential time savings of ground EMS requests for helicopter EMS (HEMS) transport of a STEMI patient directly to a PCI center, rather than usual transport to a local hospital with subsequent transfer. METHODS: Data from a multicenter retrospective chart review of STEMI patients transferred for primary PCI by a single HEMS agency over 12 months were used to model medical contact to balloon times (MCTB) for two scenarios: a direct-to-scene HEMS response and hospital rendezvous after ground EMS initiation of transfer. RESULTS: Actual MCTB median time for 36 hospital-initiated transfers was 160 minutes (range = 116 to 321 minutes). Scene response MCTB median time was estimated as 112 minutes (range = 69 to 187 minutes). The difference in medians was 48 minutes (95% confidence interval [CI] = 33 to 62 minutes). Hospital rendezvous MCTB median time was estimated as 113 minutes (range = 74 to 187 minutes). The difference in medians was 47 minutes (95% CI = 32 to 62 minutes). No patient had an actual MCTB time of less than 90 minutes; in the scene response and hospital rendezvous scenarios, 2 of 36 (6%) and 3 of 36 (8%), respectively, would have had MCTB times under 90 minutes. CONCLUSIONS: In this setting, ground EMS initiation of HEMS transfers for STEMI patients has the potential to reduce MCTB time, but most patients will still not achieve MCTB time of less than 90 minutes. PMID- 22320367 TI - A qualitative assessment of factors that influence emergency medical services partnerships in prehospital research. AB - OBJECTIVES: Recent efforts to increase emergency medical services (EMS) prehospital research productivity by focusing on reducing systems-related barriers to research participation have had limited effect. The objective of this study was to explore the barriers and motivators to participating in research at the agency and provider levels and to solicit suggestions for improving the success of prehospital research projects. METHODS: The authors conducted a qualitative exploratory study of EMS personnel using focus group and focused interview methodology. EMS personnel affiliated with the Pediatric Emergency Care Applied Research Network (PECARN) hospitals were selected for participation using a purposive sampling plan. Exploratory questioning identified identified factors that influence participation in research and suggestions for ensuring successful research partnerships. Through iterative coding and analysis, the factors and suggestions that emerged from the data were organized into a behavioral change planning model. RESULTS: Fourteen focus groups were conducted, involving 88 EMS prehospital providers from 11 agencies. Thirty-five in-depth interviews with EMS administrators and researchers were also conducted. This sample was representative of prehospital personnel servicing the PECARN catchment area and was sufficient for analytical saturation. From the transcripts, the authors identified 17 barriers and 12 motivators to EMS personnel participation in research. Central to these data were patient safety, clarity of research purpose, benefits, liability, professionalism, research training, communication with the research team, reputation, administrators' support, and organizational culture. Interviewees also made 29 suggestions for increasing EMS personnel participation in research. During data analysis, the PRECEDE/PROCEED planning model was chosen for behavioral change to organize the data. Important to this model, factors and suggestions were mapped into those that predispose (knowledge, attitudes, and beliefs), reinforce (social support and norms), and/or enable (organizational) the participation in prehospital research. CONCLUSIONS: This study identified factors that influence the participation of EMS personnel in research and gathered suggestions for improvement. These findings were organized into the PRECEDE/PROCEED planning model that may help researchers successfully plan, implement, and complete prehospital research projects. The authors provide guidance to improve the research process including directly involving EMS providers throughout, a strong theme that emerged from the data. Future work is needed to determine the validity of this model and to assess if these findings are generalizable across prehospital settings other than those affiliated with PECARN. PMID- 22320368 TI - Geographical variation in ambulance calls is associated with socioeconomic status. AB - OBJECTIVES: The main objective was to explore the relationship between socioeconomic status and the spatial distribution of ambulance calls, as modeled in the island nation of Singapore, at the Development Guide Plan (DGP) level (equivalent to census tracts in the United States). METHODS: Ambulance call data came from a nationwide registry from January to May 2006. We used a conditional autoregressive (CAR) model to create smoothed maps of ambulance calls at the DGP level, as well as spatial regression models to evaluate the relationship between the risk of calls with regional measures of socioeconomic status, such as household type and both personal and household income. RESULTS: There was geographical correlation in the ambulance calls, as well as a socioeconomic gradient in the relationship with ambulance calls of medical related (but not trauma-related) reasons. For instance, the relative risk (RR) of medical ambulance calls decreased by a factor of 0.66 (95% credible interval [CrI] = 0.56 to 0.79) for every 10% increase in the proportion of those with monthly household income S$5000 and above. The top three DGPs with the highest risk of medical-related ambulance calls were Changi (RR = 29, 95% CrI = 24 to 35), downtown core (RR = 8, 95% CrI = 6 to 9), and Orchard (RR = 5, 95% CrI = 4 to 6). CONCLUSIONS: This study demonstrates the utility of geospatial analysis to relate population socioeconomic factors with ambulance call volumes. This can serve as a model for analysis of other public health systems. PMID- 22320369 TI - The retrospective pre-post: a practical method to evaluate learning from an educational program. AB - OBJECTIVES: Program evaluation remains a critical but underutilized step in medical education. This study compared traditional and retrospective pre-post self-assessment methods to objective learning measures to assess which correlated better to actual learning. METHODS: Forty-seven medical students participated in a 4-hour pediatric resuscitation course. They completed pre and post self assessments on pediatric resuscitation and two distracter topics. Postcourse, students also retrospectively rated their understanding as it was precourse (the "retrospective pre" instrument). Changes in traditional and retrospective pre- to postcourse self-assessment measures were compared to an objectives-based multiple choice exam. RESULTS: The traditional pre to post self-assessment means showed an increase from 1.9 of 5 to 3.7 of 5 (p < 0.001); the retrospective pre to post scores also increased from 1.9 of 5 to 3.7 of 5 (p < 0.001). Although the group means were the same, individual participants demonstrated a response shift by either increasing or decreasing their traditional pre to retrospective pre scores. Scores on the 22-item objective multiple choice test also increased, from a median score of 13.0 to 18.0 (p < 0.001). There was no correlation between the change in self-assessments and objective measures as demonstrated by a Spearman correlation of -0.02 and -0.13 for the traditional and retrospective pre-post methods, respectively. Students reported fewer changes on the two distracters using the retrospective pre-post versus the traditional method (11 vs. 29). CONCLUSIONS: Students were able to accurately identify, but not quantify, learning using either traditional or retrospective pre-post "self-assessment" measures. Retrospective pre-post self-assessment was more accurate in excluding perceived change in understanding of subject matter that was not taught. PMID- 22320370 TI - More science for the new subspecialty. PMID- 22320371 TI - Sex and the CT: an evolving story of the heart. PMID- 22320372 TI - A national model for developing, implementing, and evaluating evidence-based guidelines for prehospital care. AB - In 2007, the Institute of Medicine's (IOM's) Committee on the Future of Emergency Care recommended that a multidisciplinary panel establish a model for developing evidence-based protocols for the treatment of emergency medical systems (EMS) patients. In response, the National EMS Advisory Council (NEMSAC) and the Federal Interagency Committee on EMS (FICEMS) convened a panel of multidisciplinary experts to review current strategies for developing evidence-based guidelines (EBGs) and to propose a model for developing such guidelines for the prehospital milieu. This paper describes the eight-step model endorsed by FICEMS, NEMSAC, and a panel of EMS and evidence-based medicine experts. According to the model, prehospital EBG development would begin with the input of evidence from various external sources. Potential EBG topics would be suggested following a preliminary evidentiary review; those topics with sufficient extant foundational evidence would be selected for development. Next, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology would be used to determine a quality-of-evidence rating and a strength of recommendation related to the patient care guidelines. More specific, contextualized patient care protocols would then be generated and disseminated to the EMS community. After educating EMS professionals using targeted teaching materials, the protocols would be implemented in local EMS systems. Finally, effectiveness and uptake would be measured with integrated quality improvement and outcomes monitoring systems. The constituencies and experts involved in the model development process concluded that the use of such transparent, objective, and scientifically rigorous guidelines could significantly increase the quality of EMS care in the future. PMID- 22320373 TI - Electronic versus manual data processing: evaluating the use of electronic health records in out-of-hospital clinical research. AB - OBJECTIVES: The objective was to compare case ascertainment, agreement, validity, and missing values for clinical research data obtained, processed, and linked electronically from electronic health records (EHR) compared to "manual" data processing and record abstraction in a cohort of out-of-hospital trauma patients. METHODS: This was a secondary analysis of two sets of data collected for a prospective, population-based, out-of-hospital trauma cohort evaluated by 10 emergency medical services (EMS) agencies transporting to 16 hospitals, from January 1, 2006, through October 2, 2007. Eighteen clinical, operational, procedural, and outcome variables were collected and processed separately and independently using two parallel data processing strategies by personnel blinded to patients in the other group. The electronic approach included EHR data exports from EMS agencies, reformatting, and probabilistic linkage to outcomes from local trauma registries and state discharge databases. The manual data processing approach included chart matching, data abstraction, and data entry by a trained abstractor. Descriptive statistics, measures of agreement, and validity were used to compare the two approaches to data processing. RESULTS: During the 21-month period, 418 patients underwent both data processing methods and formed the primary cohort. Agreement was good to excellent (kappa = 0.76 to 0.97; intraclass correlation coefficient [ICC] = 0.49 to 0.97), with exact agreement in 67% to 99% of cases and a median difference of zero for all continuous and ordinal variables. The proportions of missing out-of-hospital values were similar between the two approaches, although electronic processing generated more missing outcomes (87 of 418, 21%, 95% confidence interval [CI] = 17% to 25%) than the manual approach (11 of 418, 3%, 95% CI = 1% to 5%). Case ascertainment of eligible injured patients was greater using electronic methods (n = 3,008) compared to manual methods (n = 629). CONCLUSIONS: In this sample of out-of hospital trauma patients, an all-electronic data processing strategy identified more patients and generated values with good agreement and validity compared to traditional data collection and processing methods. PMID- 22320374 TI - Multitasking in emergency medicine. PMID- 22320375 TI - Humans and multitask performance: let's give credit where credit is due. PMID- 22320376 TI - Clinical pathologic conference: A 65-year-old male with left-sided chest pain. A case of an unexpected occupational hazard. AB - The authors present a case of a 65-year-old male who presented four times to the emergency department (ED) with left-sided chest pain. On the first three visits, the patient was admitted with a different diagnosis related to his chest pain. On the final visit, an abnormality on an imaging study performed in the ED led to the ultimate diagnostic test revealing the cause of the patient's symptoms. The patient's clinical presentation and ultimate clinical course are summarized, and a discussion of the differential diagnoses of his condition is presented. PMID- 22320379 TI - Oxidative stress and persistent pulmonary hypertension of the newborn treated with inhaled nitric oxide and different oxygen concentrations. AB - OBJECTIVES: The aim of this study was to determine the effects of inhaled NO with different oxygen concentrations on the inflammatory cascade in newborns with hypoxic respiratory failure secondary to persistent pulmonary hypertension. METHODS: 60 newborns received iNO and 30 of them received an initial oxygen concentration of 45% (group 1), while the other 30 newborns received an initial oxygen concentration of 80% (group 2). The levels of inflammatory cytokines (IL 6, IL-8, TNF-alpha) were measured. The clinical outcome was also recorded. RESULTS: The findings show that interleukin concentrations (IL-6, IL-8, TNF alpha) were significantly decreased between 0 and 72 hours (p < 0.01) in the newborns exposed to initial oxygen concentration of 45% and significantly increased in the other group. CONCLUSIONS: When inhaled, NO was co-administered with concentration of O(2) <45%, anti-inflammatory responses occurred, in accord with evidence in the published literature. The benefits of iNO on the clinical outcome in the current study demonstrate that inhaled NO in both groups was associated with improved short-term oxygenation. PMID- 22320381 TI - Loss of 5-hydroxymethylcytosine is accompanied with malignant cellular transformation. AB - Dysregulated DNA methylation followed by abnormal gene expression is an epigenetic hallmark in cancer. DNA methylation is catalyzed by DNA methyltransferases, and the aberrant expression or mutations of DNA methyltransferase genes are found in human neoplasm. The enzymes for demethylating 5-methylcytosine were recently identified, and the biological significance of DNA demethylation is a current focus of scientific attention in various research fields. Ten-eleven translocation (TET) proteins have an enzymatic activity for the conversion from 5-methylcytosine to 5 hydroxymethylcytosine (5-hmC), which is an intermediate of DNA demethylation. The loss-of-function mutations of TET2 gene were reported in myeloid malignancies, suggesting that impaired TET-mediated DNA demethylation could play a crucial role in tumorigenesis. It is still unknown, however, whether DNA demethylation is involved in biological properties in solid cancers. Here, we show the loss of 5 hmC in a broad spectrum of solid tumors: for example, a significant reduction of 5-hmC was found in 72.7% of colorectal cancers (CRCs) and 75% of gastric cancers compared to background tissues. TET1 expression was decreased in half of CRCs, and a large part of them was followed by the loss of 5-hmC. These findings suggest that the amount of 5-hmC in tumors is often reduced via various mechanisms, including the downregulation of TET1. Consistently, in the in vitro experiments, the downregulation of TET1 was clearly induced by oncogene-dependent cellular transformation, and loss of 5-hmC was seen in the transformed cells. These results suggest the critical roles of aberrant DNA demethylation for oncogenic processes in solid tissues. PMID- 22320382 TI - Is a 'mini' uniform code just skirting around the issues? PMID- 22320383 TI - Synthesis of densely substituted alpha,beta,gamma,delta-dienones via the Pd(II) catalyzed allylation, H-migration, and aerobic oxidative delta-hydride elimination cascade. AB - A novel protocol for the highly stereoselective synthesis of E,E alpha,beta,gamma,delta-unsaturated dicarbonyl compounds is presented. Starting from the readily available allylic alcohols and 1,3-diketones, an array of E,E alpha,beta,gamma,delta-dienones can be efficiently synthesized in high yields via Pd-catalyzed dehydrative allylation, H-migration, and aerobic oxidative delta hydride elimination cascade. In addition to the novel reaction mechanism, the use of 1:1 allylic alcohol and 1,3-diketone as reactant, 5 mol % of PdCl(2) as catalyst, and 1 atm of environmentally benign O(2) as oxidant, as well as the generation of only H(2)O byproduct, makes this protocol rapid, simple, atom efficient, and clean. PMID- 22320384 TI - Combined granulomatous slack skin/folliculotropic mycosis fungoides: case report. PMID- 22320385 TI - Annotation of a serum N-glycan library for rapid identification of structures. AB - Glycosylation is one of the most common post-translational modifications of proteins and has been shown to change with various pathological states including cancer. Global glycan profiling of human serum based on mass spectrometry has already led to several promising markers for diseases. The changes in glycan structure can result in altered monosaccharide composition as well as in the linkages between the monosaccharides. High-throughput glycan structural elucidation is not possible because of the lack of a glycan template to expedite identification. In an effort toward rapid profiling and identification of glycans, we have constructed a library of structures for the serum glycome to aid in the rapid identification of serum glycans. N-Glycans from human serum glycoproteins are used as a standard and compiled into a library with exact structure (composition and linkage), liquid chromatography retention time, and accurate mass. Development of the library relies on highly reproducible nanoLC-MS retention times. Tandem MS and exoglycosidase digestions were used for structural elucidation. The library currently contains over 300 entries with 50 structures completely elucidated and over 60 partially elucidated structures. This database is steadily growing and will be used to rapidly identify glycans in unknown biological samples. PMID- 22320386 TI - Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor. AB - Delta-lactoferrin (DeltaLf) is a transcription factor of which the expression is downregulated in cancer. It is a healthy tissue marker and a high expression level of its transcripts was correlated with a good prognosis in breast cancer. DeltaLf results from alternative promoter usage of the hLf gene leading to the production of 2 isoforms with alternative N-termini: lactoferrin, which is secreted, and DeltaLf, its nucleocytoplasmic counterpart. DeltaLf possesses antiproliferative properties and induces cell cycle arrest. It is an efficient transcription factor interacting in vivo via a DeltaLf response element found in the Skp1, Bax, DcpS, and SelH promoters. Since DeltaLf possesses different target genes, modifications in its activity or concentration may have crucial effects on cell homeostasis. Posttranslational modifications modulate DeltaLf transcription factor activity. Our earlier investigations showed that O-GlcNAcylation negatively regulates DeltaLf transcriptional activity, whilst inhibiting its ubiquitination and increasing its half-life. On the other hand, phosphorylation potentiates DeltaLf transcriptional activity. Recently, we showed that DeltaLf is also modified by SUMOylation. Therefore, cooperation and (or) competition among SUMOylation, ubiquitination, phosphorylation, and O-GlcNAcylation may contribute to the establishment of a fine regulation of DeltaLf transcriptional activity depending on the type of target gene and cellular homeostasis. PMID- 22320387 TI - Dramatic changes in ectomycorrhizal community composition, root tip abundance and mycelial production along a stand-scale nitrogen deposition gradient. AB - * Nitrogen (N) availability is known to influence ectomycorrhizal fungal components, such as fungal community composition, biomass of root tips and production of mycelia, but effects have never been demonstrated within the same forest. * We measured concurrently the abundance of ectomycorrhizal root tips and the production of external mycelia, and explored the changes in the ectomycorrhizal community composition, across a stand-scale N deposition gradient (from 27 to 43 kg N ha-1 yr-1) at the edge of a spruce forest. The N status was affected along the gradient as shown by a range of N availability indices. * Ectomycorrhizal root tip abundance and mycelial production decreased five and 10 fold, respectively, with increasing N deposition. In addition, the ectomycorrhizal fungal community changed and the species richness decreased. The changes were correlated with the measured indices of N status, in particular N deposition and N leaching. * The relationship between the altered ectomycorrhizal community, root tip abundance and mycelial production is discussed in the context of the N parameters. We suggest that increased N deposition to forests will cause large changes in ectomycorrhizal fungal community structure and functioning, which, in turn, may result in reduced N uptake by roots and fungi, and increased losses of N by leaching. PMID- 22320388 TI - Development of Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) inhibitors with potent anti-toxoplasma activity. AB - Toxoplasmosis is a disease of prominent health concern that is caused by the protozoan parasite Toxoplasma gondii. Proliferation of T. gondii is dependent on its ability to invade host cells, which is mediated in part by calcium-dependent protein kinase 1 (CDPK1). We have developed ATP competitive inhibitors of TgCDPK1 that block invasion of parasites into host cells, preventing their proliferation. The presence of a unique glycine gatekeeper residue in TgCDPK1 permits selective inhibition of the parasite enzyme over human kinases. These potent TgCDPK1 inhibitors do not inhibit the growth of human cell lines and represent promising candidates as toxoplasmosis therapeutics. PMID- 22320389 TI - Differential effect of amelogenin peptides on osteogenic differentiation in vitro: identification of possible new drugs for bone repair and regeneration. AB - Enamel matrix proteins (EMP) have been shown to promote regeneration of periodontal ligament and root cementum, and sometimes to enhance the differentiation of bone-forming cells in vitro and new bone growth in vivo. However, the inconsistent and unpredictable effects of EMP that have been reported for bone regeneration may be due to the highly variable composition of this heterogeneous material, which is comprised mainly of amelogenin and amelogenin-derived peptides. The present study has therefore examined the effects of naturally occurring low-molecular-weight (LMW) and high-molecular-weight (HMW) fractions of Emdogain((r)) (EMD; Institut Straumann, Basel, Switzerland), a commercially available form of EMP, on osteogenic differentiation of bone precursor cells in vitro. In addition, the effects of chemically synthesized specific components of LMW and HMW-namely, the tyrosine-rich amelogenin peptide (TRAP), a specific amelogenin isoform derived by proteolytic clipping, and a leucine-rich amelogenin peptide (LRAP), an isoform derived by alternative splicing-on bone-forming cell activity were also investigated. Our findings demonstrate that while TRAP suppressed the formation of bone-like mineralized nodules, LRAP upregulated osteogenic differentiation. Furthermore, synthetically produced TRAP and its unique C-terminal 12 amino acid sequence (TCT) also suppressed bone-forming cells, whereas LRAP and its unique C-terminal 23 amino acid sequence (LCT) markedly enhanced terminal differentiation of bone-forming cells. These findings suggest that the differential effects of amelogenin-derived peptide sequences present in EMP could be of potential clinical value, with the novel bioactive TCT peptide as a useful tool for limiting pathological bone cell growth and the unique LCT sequence having therapeutic benefits in the treatment of periodontal and orthopedic diseases. PMID- 22320391 TI - Short implants (6 mm) installed immediately into extraction sockets: an experimental study in dogs. AB - AIM: To evaluate the effect of implant length (6 mm vs.11 mm) on osseointegration (bone-to-implant contact) of implants installed into sockets immediately after tooth extraction. MATERIAL AND METHODS: In six Labrador dogs, the pulp tissue of the mesial roots of (3) P(3) was removed and the root canals were filled. Flaps were elevated bilaterally, the premolars hemi-sectioned and the distal roots removed. Recipient sites were prepared in the distal alveolus and a 6 mm or an 11 mm long implant was installed at the test and control sites, respectively. Non submerged healing was allowed. After 4 months of healing, block sections of the implant sites were obtained for histological processing and peri-implant tissue assessment. RESULTS: No statistically significant differences were found between test and control sites both for hard and soft tissue parameters. The bone-to implant contact evaluated at the apical region of the implants was similar as well. Although not statistically significant, the location of the top of the bony crest at the buccal aspect was more apical in relation to the implant shoulder at the test compared with the control sites (2.0 +/- 1.4 and 1.2 +/- 1.1 mm, respectively). CONCLUSIONS: Shorter implants (6 mm) present with equal osseointegration than do longer implants (11 mm). PMID- 22320392 TI - Importance of biosy of a presumed solitary skeletal metastasis: enchondroma in a breast cancer patient. PMID- 22320393 TI - RCL2, a potential formalin substitute for tissue fixation in routine pathological specimens. AB - AIMS: To investigate RCL2 as a fixative for tissue fixation in routine histopathological examination and to assess tissue suitability for ancillary investigations. METHODS AND RESULTS: Forty-nine samples from 36 fresh specimens were cut into three equal pieces and fixed in RCL2 diluted in 100% ethanol, RCL2 in 95% ethanol, or neutral buffered formalin as control. Suitability for microtomy, quality of histomorphology, histochemistry, immunohistochemistry, fluorescent and silver in-situ hybridization analysis and extracted genomic DNA were assessed. Microtomy was straightforward in most tissue blocks, but there was difficulty in cutting in approximately a quarter of samples, which required careful handling by an experienced technician. There were no significant differences in tissue morphology between RCL2- and formalin-fixed tissues (P=0.08). Generally, the quality of histochemical staining, immunohistochemistry and in-situ hybridization were comparable to that of formalin-fixed tissues. Inconsistent immunoreactivity was noted, however, with antibodies against pan cytokeratin and progesterone receptor. Genomic DNA concentration was higher in RCL2-fixed tissues. Using RCL2 diluted in 95% ethanol did not affect fixation quality. CONCLUSION: RCL2 is a potential formalin substitute suitable as a fixative for use in routine histopathological examination; however, difficulty in microtomy and occasional discrepancies in immunohistochemical reactivity require further optimization of the methodology. PMID- 22320394 TI - Editorial: What has Florence Nightingale ever done for clinical nurses? PMID- 22320395 TI - Therapeutic hypothermia in a late preterm infant. AB - Therapeutic hypothermia is a recognized treatment for term infants with hypoxic ischemic encephalopathy (HIE) in reducing rate of death or neurodevelopmental disabilities. Little is known about applications of this treatment to preterm newborns. Studies in animal experimental models demonstrated the efficacy of hypothermia in preterm fetuses but clinical application to newborn infants are limited to restricted cases, as severe necrotizing enterocolitis (NEC). We present a case of therapeutic whole body cooling in a baby at 34 weeks and 6 days of gestational age with HIE. PMID- 22320396 TI - Cutaneous complications following transcatheter arterial chemoembolization. PMID- 22320397 TI - Design of NIR-absorbing simple asymmetric squaraine dyes carrying indoline moieties for use in dye-sensitized solar cells with Pt-free electrodes. AB - Novel near-infrared (NIR)-sensitizing (up to 800 nm) simple asymmetric squaraine dyes (Sq 31 and Sq 33) carrying indoline moieties that did not require the introduction of any linker groups were developed. DSSCs fabricated with Sq 33 exhibited remarkable characteristics in the long-wavelength visible and NIR region (up to 800 nm), such as a conversion efficiency of 3.75% (AM 1.5G) with an incident photon-to-current conversion efficiency of 63% (650 nm), a short-circuit photocurrent density of 13.64 mA, an open-circuit photovoltage of 0.48, and a fill factor of 0.57. PMID- 22320398 TI - Coexpression of MUC16 and mesothelin is related to the invasion process in pancreatic ductal adenocarcinoma. AB - The invasion process is a crucial step for pancreatic ductal adenocarcinoma (PDAC); however, the genes related to invasion remain unclear. To identify specific genes for the invasion process, we compared microarray data for infiltrating cancer and PanIN-3, which were harvested from an individual PDAC patient by microdissection. Furthermore, immunohistochemical, coimmunoprecipitation and invasion analyses were performed to confirm the biologic significance of molecules identified by expression profile. In the present study, we focused on MUC16 and mesothelin among 87 genes that were significantly upregulated in infiltrating components compared to PanIN-3 in all PDAC patients, because MUC16 was the most differently expressed between two regions, and mesothelin was reported as the receptor for MUC16. Immunohistochemical analysis revealed that MUC16 and mesothelin were expressed simultaneously only in infiltrating components and increased at the invasion front, and binding of MUC16 and mesothelin was found in PDAC by immunoprecipitation assay. The downregulation of MUC16 by shRNA and the blockage of MUC16 binding to mesothelin by antibody inhibited both invasion and migration of pancreatic cancer cell line. MUC16 high/mesothelin high expression was an independent prognostic factor for poor survival in PDAC patients. In conclusion, we identified two specific genes, MUC16 and mesothelin, associated with the invasion process in patients with PDAC. PMID- 22320399 TI - Role of individual phosphorylation sites for the 14-3-3-protein-dependent activation of yeast neutral trehalase Nth1. AB - Trehalases are important highly conserved enzymes found in a wide variety of organisms and are responsible for the hydrolysis of trehalose that serves as a carbon and energy source as well as a universal stress protectant. Emerging evidence indicates that the enzymatic activity of the neutral trehalase Nth1 in yeast is enhanced by 14-3-3 protein binding in a phosphorylation-dependent manner through an unknown mechanism. In the present study, we investigated in detail the interaction between Saccharomyces cerevisiae Nth1 and 14-3-3 protein isoforms Bmh1 and Bmh2. We determined four residues that are phosphorylated by PKA (protein kinase A) in vitro within the disordered N-terminal segment of Nth1. Sedimentation analysis and enzyme kinetics measurements show that both yeast 14-3 3 isoforms form a stable complex with phosphorylated Nth1 and significantly enhance its enzymatic activity. The 14-3-3-dependent activation of Nth1 is significantly more potent compared with Ca2+-dependent activation. Limited proteolysis confirmed that the 14-3-3 proteins interact with the N-terminal segment of Nth1 where all phosphorylation sites are located. Site-directed mutagenesis in conjunction with the enzyme activity measurements in vitro and the activation studies of mutant forms in vivo suggest that Ser60 and Ser83 are sites primarily responsible for PKA-dependent and 14-3-3-mediated activation of Nth1. PMID- 22320400 TI - Isolating a trimer intermediate in the self-assembly of E2 protein cage. AB - Understanding the self-assembly mechanism of caged proteins provides clues to develop their potential applications in nanotechnology, such as a nanoscale drug delivery system. The E2 protein from Bacillus stearothermophilus , with a virus like caged structure, has drawn much attention for its potential application as a nanocapsule. To investigate its self-assembly process from subunits to a spherical protein cage, we truncate the C-terminus of the E2 subunit. The redesigned protein subunit shows dynamic transition between monomer and trimer, but not the integrate 60-mer. The results indicate the role of the trimer as the intermediate and building block during the self-assembly of the E2 protein cage. In combination with the molecular dynamics simulations results, we conclude that the C-terminus modulates the self-assembly of the E2 protein cage from trimer to 60-mer. This investigation elucidates the role of the intersubunit interactions in engineering other functionalities in other caged structure proteins. PMID- 22320401 TI - Profiling and identification of cerebrospinal fluid proteins in a rat EAE model of multiple sclerosis. AB - The experimental autoimmune encephalomyelitis (EAE) model resembles certain aspects of multiple sclerosis (MScl), with common features such as motor dysfunction, axonal degradation, and infiltration of T-cells. We studied the cerebrospinal fluid (CSF) proteome in the EAE rat model to identify proteomic changes relevant for MScl disease pathology. EAE was induced in male Lewis rats by injection of myelin basic protein (MBP) together with complete Freund's adjuvant (CFA). An inflammatory control group was injected with CFA alone, and a nontreated group served as healthy control. CSF was collected at day 10 and 14 after immunization and analyzed by bottom-up proteomics on Orbitrap LC-MS and QTOF LC-MS platforms in two independent laboratories. By combining results, 44 proteins were discovered to be significantly increased in EAE animals compared to both control groups, 25 of which have not been mentioned in relation to the EAE model before. Lysozyme C1, fetuin B, T-kininogen, serum paraoxonase/arylesterase 1, glutathione peroxidase 3, complement C3, and afamin are among the proteins significantly elevated in this rat EAE model. Two proteins, afamin and complement C3, were validated in an independent sample set using quantitative selected reaction monitoring mass spectrometry. The molecular weights of the identified differentially abundant proteins indicated an increased transport across the blood-brain barrier (BBB) at the peak of the disease, caused by an increase in BBB permeability. PMID- 22320402 TI - Amine linked flavonoid dimers as modulators for P-glycoprotein-based multidrug resistance: structure-activity relationship and mechanism of modulation. AB - Here we report a great improvement in reversal potency of cancer drug resistance when flavonoid dimers possess a functionally substituted aminopolyethylene glycol linker. The most potent compound, 18, contains a N-benzyl group at the linker. It has many advantages including (1) high potencies in reversing P-glycoprotein (P gp) mediated resistance in LCC6MDR cells to various anticancer drugs with EC(50) in the nanomolar range, (2) low toxicity and high therapeutic index, and (3) preferential inhibition of P-gp over multidrug resistance protein 1 and breast cancer resistance protein. Compound 18 stimulates P-gp-ATPase activity by 2.7 fold and mediates a dose-dependent inhibition of doxorubicin (DOX) transport activity. Lineweaver-Burk and Dixon plots suggest that 18 is a competitive inhibitor to DOX in binding to P-gp with a K(i) of 0.28-0.34 MUM and a Hill coefficient of 1.17. Moreover, the LCC6MDR cell displays about 2.1-fold lower intracellular accumulation of 18 compared to the wild type, suggesting that 18 is a P-gp substrate as well. PMID- 22320404 TI - Effect of ultrasound-facilitated fixation on oral mucosa density and morphology. AB - We investigated the effects of ultrasound-facilitated fixation on oral mucosal morphology. Bovine dorsal tongue and porcine buccal (cheek) mucosa were sonicated for 0, 5, 10 or 15 min in a modified methacarn fixative, then incubated at 25 degrees C for 4 h. Initial mass, volume and density of each specimen were measured before and after treatment and fixation. Morphometric analysis of the scanning electron micrographs was used to quantify changes in mucosal structure and microtexture. Statistical methods were used to describe the relation between sonication time, tissue density and relative change in tissue density. Our results indicate a linear correlation between sonication time and density of the dorsal tongue specimens. The treatment caused contraction of the tongue tissue and expansion of the buccal mucosa. Differences between initial and final tongue densities and the relative change in tissue density of the tongue vs. buccal mucosa were statistically significant. Differences observed between initial and final buccal mucosa densities were not statistically significant. Changes in buccal mucosa density correlated inversely with sonication time by contrast to the tongue density, which was correlated directly with this factor. Our study illustrates that while preservation of mucosal morphology and biopolymers can be achieved by ultrasound-facilitated fixation, its effects on tissue density are both time-dependent and specific to certain regions of the mouth. PMID- 22320405 TI - Adhesive performance of silver-palladium-copper-gold alloy and component metals bonded with organic sulfur-based priming agents and a tri-n-butylborane initiated luting material. AB - OBJECTIVE: The purpose of the current study was to evaluate the effect of thione based metal priming agents on the adhesive behavior of a Ag-Pd-Cu-Au alloy and component metals bonded with an acrylic resin. MATERIALS AND METHODS: Disk specimens (10 mm in diameter by 3 mm thick) were prepared from a silver-palladium copper-gold (Ag-Pd-Cu-Au) alloy (Castwell M.C.12), high-purity silver, palladium, copper and gold. Four single-liquid priming agents containing organic sulfur compound (Alloy Primer, Metaltite, M.L. Primer and V-Primer) and three acidic priming agents (All Bond II Primer B, Estenia Opaque Primer and Super-Bond Liquid) were assessed. The metal specimens were flat-ground with abrasive papers, primed with one of the agents and bonded with a tri-n-butylborane initiated resin. The shear bond strengths were determined both before and after repeated thermocycling (5 degrees C and 55 degrees C, 1 min each, 20,000 cycles). The results were statistically analyzed with a non-parametric procedure (p = 0.05 level). RESULTS: The post-thermocycling bond strengths in MPa (median; n = 11) associated with the Alloy Primer, Metaltite, M.L. Primer and V-Primer materials were, respectively, 20.8, 22.8, 17.8 and 18.4 for the Ag-Pd-Cu-Au alloy; 19.6, 21.9, 14.4 and 20.1 for silver; 5.4, 4.5, 12.8 and 5.3 for palladium; 17.1, 19.2, 0.7 and 6.6 for copper; and 18.5, 17.7, 22.8 and 15.4 for gold. CONCLUSIONS: It can be concluded that the use of the four priming agents, which are based on organic sulfur compounds, effectively enhanced bonding to the Ag-Pd-Cu-Au alloy and the component metals, although the bonding performance varied among the priming agents and metal elements. The priming agents appeared to have more of an effect on the alloy, silver and gold than on the palladium and copper. PMID- 22320406 TI - alpha-6 integrin expression in bovine spermatogonial cells purified by discontinuous Percoll density gradient. AB - The study of spermatogonial stem cells (SSCs) provides a model to better understand adult stem cell biology. Besides the biomedical potential to perform studies of infertility in many species, SSCs hold a promising application at animal transgenesis. Because stem cells are thought to be associated with basement membranes, expression of alpha-6 integrin has been investigated as a marker of type A spermatogonial cells, which are considered SSCs because of their undifferentiated status and self-renewal ability. In this manner, the aim of this study was to isolate type A SSCs from adult bulls by a two-step enzymatic procedure followed by a discontinuous Percoll density gradient purification and verify the expression of alpha-6 integrin by flow cytometry and real-time RT-PCR before and after Percoll purification. Spermatogonial cells were successfully obtained using the two-step enzymatic digestion. An average of 1 * 10(5) viable cells per gram of testis was isolated. However, the discontinuous Percoll did not purify isolated cells regarding alpha-6 integrin expression. Flow cytometry analysis demonstrated no differences in the alpha-6 integrin expression between cell samples before and after Percoll purification (p = 0.5636). The same was observed in the real-time PCR analysis (p > 0.05). In addition to alpha-6 integrin, the expression of GFRa-1 and PGP9.5, known bovine SSCs markers, was detected in all samples studied. Considering that Percoll can reduce cell viability, it is possible to conclude that Percoll density gradient is not suitable to purify bovine SSC, according to alpha-6 integrin expression. PMID- 22320407 TI - Deletion of MP/ARF5 domains III and IV reveals a requirement for Aux/IAA regulation in Arabidopsis leaf vascular patterning. AB - Combinatorial interactions of AUXIN RESPONSE FACTORs (ARFs) and auxin/indole acetic acid (Aux/IAA) proteins through their common domains III and IV regulate auxin responses, but insight into the functions of individual proteins is still limited. As a new tool to explore this regulatory network, we generated a gain-of function ARF genotype by eliminating domains III and IV from the functionally well-characterized ARF MONOPTEROS(MP)/ARF5. This truncated version of MP, termed MPDelta, conferred complementing MP activity, but also displayed a number of semi dominant traits affecting auxin signaling and organ patterning. In MPDelta, the expression levels of many auxin-inducible genes, as well as rooting properties and vascular tissue abundance, were enhanced. Lateral organs were narrow, pointed and filled with parallel veins. This effect was epistatic over the vascular hypotrophy imposed by certain Aux/IAA mutations. Further, in MPDelta leaves, failure to turn off the procambium-selecting gene PIN1 led to the early establishment of oversized central procambial domains and very limited subsequent lateral growth of the leaf lamina. We conclude that MPDelta can selectively uncouple a single ARF from regulation by Aux/IAA proteins and can be used as a genetic tool to probe auxin pathways and explore leaf development. PMID- 22320408 TI - The association of 2-year-old training milestones with career length and racing success in a sample of Thoroughbred horses in New Zealand. AB - REASONS FOR PERFORMING STUDY: There is increasing evidence that exercise early in life has a positive effect on musculoskeletal health. At present, there is little whole population research investigating the effect of racing as 2-year-olds on future racing career. OBJECTIVES: To investigate the association between attaining training milestones as 2-year-olds with length of career and racing success in Thoroughbred horses in New Zealand. METHODS: Retrospective data were obtained of the 2001/02-born Thoroughbred foal crop. The 3 training milestones were: registered with a trainer, trialled and raced. The association of the training milestones with career length was measured using the outcomes: number of race starts and number of years raced, in a Cox regression model. Logistic regression models analysed the association of the training milestones with the outcomes: won or placed in a race. Linear regression was performed to assess the association of training milestones with total career earnings. RESULTS: Of 4683 horses in the population; 3152 horses were registered with a trainer, 2661 horses trialled and 2109 horses raced. Horses that raced as 2-year-olds had significantly (P<0.001) more race starts than those first raced as 3-year-olds or older, this was also true when the 2-year-old year data were omitted. Horses that raced as 2-year-olds had significantly (P<0.001) more years racing. Horses registered with a trainer, trialled or raced as 2-year-olds were more likely to have won or been placed in a race than those that achieved the milestones as 3 year-olds or older. Horses that first trialled and raced as 2-year-olds had greater total earnings than those that first trialled or raced at a later age. CONCLUSIONS AND POTENTIAL RELEVANCE: Two-year-old training milestones had a strong association with positive racing career outcomes. Horses in training or racing as 2-year-olds may have better musculoskeletal health throughout life than horses that are first in training or racing at a later age. PMID- 22320409 TI - Comparison of sedative drugs under peribulbar or topical anesthesia during phacoemulsification. AB - BACKGROUND AND OBJECTIVE: To compare dexmedetomidine and midazolam+fentanyl sedation primarily based on patient satisfaction during phacoemulsification under topical and peribulbar anesthesia. PATIENTS AND METHODS: Prospective, randomized, and double-blind study of 80 American Society of Anesthesiology grade I-II patients who underwent phacoemulsification with local anesthesia under sedation. Patients were divided into four groups (20 patients for each): dexmedetomidine and topical anesthesia, dexmedetomidine and peribulbar anesthesia, midazolam+fentanyl and topical anesthesia, and midazolam+fentanyl and peribulbar anesthesia. Patient and surgeon satisfaction were determined on a 5-point scale. The pain was determined by verbal pain scale intraoperatively and postoperatively. Drugs were given to a Ramsay sedation scale of 3. Topical and peribulbar anesthesia were performed by an ophthalmologist. Hemodynamic, respiratory, and intraocular pressure monitoring was done. Operative and recovery times were recorded. RESULTS: In the midazolam+fentanyl groups, better patient and surgeon satisfaction scores were obtained (P < .005), verbal pain scale scores were significantly lower (P < .001), and patients needed less postoperative analgesia. Ramsay sedation scale scores were between 3 and 4 in all patients and there were no significant differences. Intraocular pressure alterations were similar between groups. Recovery time was longer in the dexmedetomidine groups (P < .05). CONCLUSION: The study demonstrated that the midazolam+fentanyl combination provided high-level patient satisfaction scores, low-level pain scores, and shorter recovery time. Also, both of the peribulbar and topical anesthesia procedures showed similar efficiency. PMID- 22320410 TI - Nd:YAG laser treatment for epithelial ingrowth after laser refractive surgery. AB - Epithelial ingrowth under refractive surgery flaps occurs in primary treatment and in further flap lift. Nd:YAG treatment was first described in 2008. In the only series published to date, 100% of patients treated had topographic and symptomatic improvement. The authors pictorially illustrate two cases of epithelial ingrowth following laser in situ keratomileusis achieving complete symptomatic relief and marked microscopic improvement following Nd:YAG laser treatment. PMID- 22320412 TI - Multi-purpose extraocular forceps for small-gauge pars plana vitrectomy. AB - A multi-purpose titanium forceps has been developed for small-gauge pars plana vitrectomy surgery. These forceps were designed to provide the vitreoretinal surgeon with a single tool for the extraocular manipulations that are necessary for the placement and removal of 23- and 25-gauge trochars for small-incision, sutureless pars plana vitrectomy surgery. The forceps has been designed to allow for the atraumatic manipulation of the conjunctiva, measurement of distance from the limbus, and a strong purchase of the trochar for both its fixation and removal. PMID- 22320411 TI - Anterior segment dimensions in Asian and Caucasian eyes measured by optical coherence tomography. AB - BACKGROUND AND OBJECTIVE: To compare Asian and Caucasian anterior segment dimensions measured by optical coherence tomography (OCT). PATIENTS AND METHODS: Anterior segment OCT images were obtained in normal subjects. Four line scans were acquired at the 90 degrees , 45 degrees , 0 degrees , and 135 degrees meridians of each eye. Computer calipers acquired anterior segment dimensions of corneal diameter, anterior chamber width, corneal vault, and anterior chamber depth on OCT images. Univariate and multivariate analyses were performed to assess correlations. RESULTS: Corneal diameter was 0.5 mm narrower (P < .01), anterior chamber width was 0.46 mm narrower (P < .01), and corneal vault was 0.22 mm lower (P < .01) in Asian eyes. All anterior segment dimensions decreased with age. CONCLUSION: Asian eyes had smaller anterior segments compared to Caucasian eyes. Regardless of race, anterior segment dimensions were smaller in older subjects. Age-related changes may affect the tolerability of long-term implants such as phakic intraocular lenses. PMID- 22320413 TI - Macular hole surgery prognostic success rates based on macular hole size. AB - BACKGROUND AND OBJECTIVE: To evaluate the correlation between macular hole (MH) surgery outcomes and preoperative factors believed to affect surgical success rates. PATIENTS AND METHODS: A retrospective, consecutive case series was designed to evaluate the correlation between anatomic success and preoperative factors: MH duration prior to surgery, visual acuity (VA), and MH diameter measured by optical coherence tomography (OCT) at the base and the narrowest midpoint. RESULTS: A total of 153 eyes were enrolled. There was no significant difference in mean duration prior to surgery for MH success and failure (P = .13). Mean preoperative VA was significantly better for MH success than failure (P = .03). Mean mid-hole diameter (P < .001) and mean base-hole diameter (P < .001) were significantly less for MH success than failure. Failure rate was 0% among eyes with mid-hole diameter less than 500 microns and 14.9% with mid-hole 500 microns or greater (P < .001). Failure rate was 0% among eyes with base-hole diameter less than 500 microns, 1.4% with base-hole 500 to 999 microns, and 19.1% with base-hole of 1,000 microns or greater (P = .001). CONCLUSION: Preoperative VA, mid-hole diameter, and base-hole diameter are correlated with anatomic success in MH surgery. An excellent surgical prognosis exists for MHs with mid hole diameter less than 500 microns and base-hole less than 1,000 microns. PMID- 22320414 TI - Difference in morning and evening choroidal thickness in Japanese subjects with no chorioretinal disease. AB - BACKGROUND AND OBJECTIVE: To determine whether the choroidal thickness varies significantly according to the time of measurement in Japanese subjects without chorioretinal diseases. PATIENTS AND METHODS: Twelve eyes of 12 subjects were examined with enhanced depth imaging spectral-domain optical coherence tomography. The choroidal thickness was measured in the mornings (9:00 to 9:30 AM) and evenings (7:30 to 8:00 PM) at three locations: the fovea, 1.5 mm temporal to the fovea, and 1.5 mm nasal to the fovea. RESULTS: The mean age of the subjects was 62.6 +/- 14.5 years. For the morning measurements, the mean choroidal thickness was 308.5 +/- 74.4 MUm at the fovea, 276.2 +/- 84.6 MUm temporally, and 239.3 +/- 98.4 MUm nasally. For the evening measurements, the mean choroidal thickness was 328.8 +/- 85.6 MUm at the fovea, 284.8 +/- 91.6 MUm temporally, and 248.9 +/- 101.5 MUm nasally. The mean subfoveal (P < .0001) and nasal (P = .03) choroidal thicknesses were significantly thicker in the evenings than in the mornings. There was no significant difference in the mean temporal choroidal thickness (P = .08). CONCLUSION: The choroidal thickness varies according to the time of measurement. PMID- 22320415 TI - Staggered sub-Tenon's blocks: a novel anesthetic approach for bilateral strabismus surgery. AB - Bilateral strabismus surgery is usually performed under general anesthesia. However, sometimes general anesthesia is not in the best interest of patients presenting with advanced multiple comorbidities. These patients are best treated with local anesthesia instead. However, the bilateral nature of the surgery becomes an issue because bilateral akinetic needle blocks for ophthalmic surgery have not been described before. This article describes a novel approach for bilateral eye surgery in three patients who were at high risk from general anesthesia but needed to have the surgery performed in the same sitting. Staggered blunt needle sub-Tenon's blocks were chosen over sharp needle akinetic extraconal peribulbar or intraconal retrobulbar blocks on account of their predictability, relative safety, and efficacy. The potential systemic complications of bilateral injections were minimized by staggering the blocks. This technique may be an option for high-risk patients who are not candidates for general anesthesia but require bilateral ophthalmic surgery performed in a single surgical episode. PMID- 22320416 TI - Comparison of central corneal thickness measurements by Galilei Dual-Scheimpflug analyzer(r) and ultrasound pachymeter in myopic eyes. AB - BACKGROUND AND OBJECTIVE: To compare the central corneal thickness (CCT) measurements by Galilei Dual-Scheimpflug analyzer (GSA) (Ziemer Group, Port, Switzerland) and ultrasound pachymeter (UP) in myopic eyes. PATIENTS AND METHODS: In this prospective study, CCT of 161 myopic eyes of 81 refractive surgery candidates (35 female, 46 male; mean age: 23.18 +/- 4.08 years) were measured by GSA and UP consecutively. The data were analyzed statistically by paired t test, Bland-Altman plot, and Pearson correlation test to assess the agreement of the measurements. RESULTS: The mean CCTs obtained by GSA and UP were 559.85 +/- 30.87 and 560.41 +/- 34.45 MUm, respectively. No significant difference was found between the measurements (P = .684) and regression analysis showed a high correlation between the measurements obtained with both devices (r = 0.86; P < .001). A strong agreement between the two methods was also found by Bland-Altman plot. CONCLUSION: In myopic eyes, the CCT measurements of GSA and UP are similar and highly correlated. Because of high agreement between these devices, the GSA is a non-contact method that may be an alternative to UP for measurement of CCT. PMID- 22320417 TI - Diagnosis of Type-I hiatal hernia: a comparison of high-resolution manometry and endoscopy. AB - Sliding Type-I hiatal hernia is commonly diagnosed using upper endoscopy, barium swallow or less commonly, esophageal manometry. Current data suggest that endoscopy is superior to barium swallow or esophageal manometry. Recently, high resolution manometry has become available for the assessment of esophageal motility. This novel technology is capable of displaying spatial and topographic pressure profiles of gastroesophageal junction and crural diaphragm in real time. The objective of the current study was to compare the specificity and sensitivity of high-resolution manometry and endoscopy in the diagnosis of sliding hiatal hernia in patients with gastroesophageal reflux disease. Data were analyzed retrospectively for 83 consecutive patients (61% females, mean age 52 +/- 13.2 years) with objective gastroesophageal reflux disease who were considered for laparoscopic antireflux surgery between January 2006 and January 2009 and had preoperative high-resolution manometry and endoscopy. Manometrically, hiatal hernia was defined as separation of the gastroesophageal junction >2.0 cm from the crural diaphragm. Intraoperative diagnosis of hiatal hernia was used as the gold standard. Sensitivity, specificity and likelihood ratios of a positive test and a negative test were used to compare the performance of the two diagnostic modalities. Forty-two patients were found to have a Type-I sliding hiatal hernia (>2 cm) during surgery. Twenty-two patients had manometric criteria for a hiatal hernia by high-resolution manometry, and 36 patients were described as having a hiatal hernia by preoperative endoscopy. False positive results were significantly fewer (higher specificity) with high-resolution manometry as compared with endoscopy (4.88% vs. 31.71%, P= 0.01). There were no significant differences in the false negative results (sensitivity) between the two diagnostic modalities (47.62% vs. 45.24%, P= 0.62). Analysis of likelihood ratios of a positive and negative test demonstrated that high-resolution manometry is better than endoscopy both to rule out and rule in a hiatal hernia. A significant discordance was also observed between the two tests (P= 0.033). High-resolution manometry has better specificity and ability to rule out an overt Type-I sliding hiatal hernia (greater likelihood ratio of a positive test) in patients with GERD. Because of high false negative results, both high-resolution manometry and endoscopy are unreliable for ruling in a hiatal hernia. Negative result for a hiatal hernia by either modality mandates additional testing. PMID- 22320418 TI - Comparison of dorzolamide/timolol and latanoprost/timolol fixed combinations on diurnal intraocular pressure control in primary open-angle glaucoma. AB - PURPOSE: To compare the efficacy and safety of dorzolamide hydrochloride 2%/timolol maleate 0.5% fixed combination (DTFC) with latanoprost 0.005%/timolol maleate 0.5% fixed combination (LTFC) on diurnal intraocular pressure (IOP) in patients with primary open-angle glaucoma. METHODS: Thirty-three primary open angle glaucoma patients with IOP of 22-32 mmHg measured at any time were included. Patients were randomized to either DTFC twice daily or latanoprost 0.005%/timolol maleate 0.5% fixed combination (LTFC) once a day in the evening. After a 6-week treatment period with each combination, IOP were measured every 4 h during 24 h (first diurnal curve) and after 6 weeks of washout period, the patients were switched to the other treatment for 6 weeks of the second diurnal curve. RESULTS: The mean baseline IOP was 25.09+/-2.8 mmHg. After the treatment period, mean diurnal IOP was statistically lower with LTFC (16.3 mmHg) than with DTFC (17.3 mmHg), and the peak IOP value was 18.5 mmHg with LTFC and 19.9+/-2.6 mmHg with DTFC (P<0.05). No significant side effects were reported except stinging and bitter taste with the DTFC group. CONCLUSION: Mean diurnal IOP and peak IOP were lower with LTFC than with DTFC in patients with primary open-angle glaucoma. PMID- 22320419 TI - New mucoadhesive chitosan film for ophthalmic drug delivery of timolol maleate: in vivo evaluation. AB - PURPOSE: Chitosan, a cationic polysaccharide biopolymer with mucoadhesive properties, presents a promising future in the prolonged ocular delivery of drugs. The present study compared the efficacy and safety of chitosan-coated timolol maleate (TM) mucoadhesive film, using a 0.5% TM commercial ophthalmic solution in a rabbit model. In addition, this study investigates the maximum release time of these implants in vivo. METHODS: The mucoadhesive films were prepared by means of a casting and solvent evaporation technique performed in a 2 wt% acetic acid solution and distilled water. Physical properties were characterized by release and swelling studies, differential scanning calorimetry, and attenuated total reflectance fourier transformed infrared spectroscopy (ATR FTIR). The developed formulations were evaluated for their pharmacodynamics in ocular normotensive albino rabbits, in which the intraocular pressure (IOP) was measured by means of applanation tonometer on alternative days (13 h) for 11 weeks. For 15 days, 0.5% TM commercial ophthalmic solution was administered twice a day (n=5) and compared to chitosan-coated TM (n=5). In the control group (n=5), saline was used twice a day. The maximum TM release time from chitosan films were also recorded. After euthanasia, the right eyes were removed from the 3 groups for histological analyses. RESULTS: In an in vitro study, TM was released over a 4-week period, in which 85% of the drug was released over the first 2 weeks. However, the film's release of TM lowered the in vivo IOP levels over a 10-week period. No significant difference in the lowering of IOP in rabbits treated with 0.5% TM commercial ophthalmic solution, as compared to those that received the films (P<0.05), could be observed. No signs of ocular discomfort or irritations could be identified upon ophthalmic examination by slit-lamp biomicroscopy. Ophthalmic structures that came in direct contact with the films revealed no alterations within the histopathological studies. Moreover, the animals showed no signs of ocular discomfort during the experimental assays. CONCLUSION: These findings suggest that the TM-loaded chitosan film is safe and efficient and presents a promising future as an ocular drug delivery system in the treatment and prevention of glaucoma. PMID- 22320420 TI - Editorial: Learning is still the real business of the University. PMID- 22320421 TI - The ecology of Anopheles mosquitoes under climate change: case studies from the effects of deforestation in East African highlands. AB - Climate change is expected to lead to latitudinal and altitudinal temperature increases. High-elevation regions such as the highlands of Africa and those that have temperate climate are most likely to be affected. The highlands of Africa generally exhibit low ambient temperatures. This restricts the distribution of Anopheles mosquitoes, the vectors of malaria, filariasis, and O'nyong'nyong fever. The development and survival of larval and adult mosquitoes are temperature dependent, as are mosquito biting frequency and pathogen development rate. Given that various Anopheles species are adapted to different climatic conditions, changes in climate could lead to changes in species composition in an area that may change the dynamics of mosquito-borne disease transmission. It is important to consider the effect of climate change on rainfall, which is critical to the formation and persistence of mosquito breeding sites. In addition, environmental changes such as deforestation could increase local temperatures in the highlands; this could enhance the vectorial capacity of the Anopheles. These experimental data will be invaluable in facilitating the understanding of the impact of climate change on Anopheles. PMID- 22320422 TI - Can theophylline be an alternative antidote for amitriptyline toxicity? PMID- 22320423 TI - Elevated level of lysine 9-acetylated histone H3 at the MDR1 promoter in multidrug-resistant cells. AB - Failure of chemotherapy in breast cancer presents a major problem and is often due to elevated expression of ATP binding cassette (ABC)-type transporters, such as MDR1 protein. It has been shown that MDR1/ABCB1 gene expression is regulated at the chromatin level by DNA methylation and histone acetylation. However, the modified histone residues have not been identified and the role of various histone acetyl transferases (HATs) is not fully understood. By studying a breast carcinoma model cell line and its MDR1-overexpressing derivative, we show that the histone 3 lysine 9 (H3K9) acetylation level is elevated 100-fold in the promoter and first exon of the MDR1 gene in the drug-resistant cell line compared to the drug-sensitive cell line. The acetylation level of the other examined lysine residues (H3K4, H3K14, H4K8, and H4K12) is weakly or not at all elevated in the MDR1 locus, although their acetylation is generally increased genome-wide in the drug-resistant cell. Downregulation of the expression of HATs PCAF and GCN5 by RNAi effectively reduces the expression of MDR1. Unexpectedly, treatment with a p300-selective inhibitor (HAT inhibitor II) further increases MDR1 expression and drug efflux in the drug-resistant cells. Our data suggest that repeated exposure to chemotherapy may result in deregulated histone acetylation genome-wide and in the MDR1 promoter. PMID- 22320424 TI - Palladium-catalyzed direct hydroxymethylation of aryl halides and triflates with potassium acetoxymethyltrifluoroborate. AB - Suzuki-Miyaura cross-coupling reactions of aryl halides and triflates with potassium acetoxymethyltrifluoroborate afforded the corresponding aryl and heteroaryl methanol products in moderate to excellent yields. PMID- 22320426 TI - Crystal structure of the enzyme CapF of Staphylococcus aureus reveals a unique architecture composed of two functional domains. AB - CP (capsular polysaccharide) is an important virulence factor during infections by the bacterium Staphylococcus aureus. The enzyme CapF is an attractive therapeutic candidate belonging to the biosynthetic route of CP of pathogenic strains of S. aureus. In the present study, we report two independent crystal structures of CapF in an open form of the apoenzyme. CapF is a homodimer displaying a characteristic dumb-bell-shaped architecture composed of two domains. The N-terminal domain (residues 1-252) adopts a Rossmann fold belonging to the short-chain dehydrogenase/reductase family of proteins. The C-terminal domain (residues 252-369) displays a standard cupin fold with a Zn2+ ion bound deep in the binding pocket of the beta-barrel. Functional and thermodynamic analyses indicated that each domain catalyses separate enzymatic reactions. The cupin domain is necessary for the C3-epimerization of UDP-4-hexulose. Meanwhile, the N-terminal domain catalyses the NADPH-dependent reduction of the intermediate species generated by the cupin domain. Analysis by ITC (isothermal titration calorimetry) revealed a fascinating thermodynamic switch governing the attachment and release of the coenzyme NADPH during each catalytic cycle. These observations suggested that the binding of coenzyme to CapF facilitates a disorder-to-order transition in the catalytic loop of the reductase (N-terminal) domain. We anticipate that the present study will improve the general understanding of the synthesis of CP in S. aureus and will aid in the design of new therapeutic agents against this pathogenic bacterium. PMID- 22320427 TI - Intraspecific trait cospecialization of constitutive and inducible morphological defences in a marine snail from habitats with different predation risk. AB - 1. Studies examining the integration of constitutive and inducible aspects of multivariate defensive phenotypes are rare. 2. I asked whether marine snails (Nucella lamellosa) from habitats with and without abundant predatory crabs differed in constitutive and inducible aspects of defensive shell morphology. 3. I examined multivariate shell shape development of snails from each habitat in the presence and absence of waterborne cues from feeding crabs (Cancer productus). I also examined the influence of constitutive and inducible shell morphology on resistance to crushing. 4. Regardless of the presence of crabs, snails from high-risk (HR) habitats developed rotund, short-spired shells, while snails from low-risk habitats developed elongate shells, tall-spired shells, indicating among-habitat divergence in constitutive shell shape. Moreover, allometry analyses indicated that constitutive developmental patterns underlying this variation also differed between habitats. However, snails from HR habitats showed greater plasticity for apertural lip thickness and apertural area in the presence of crab cues, indicating among-habitat variation in defence inducibility. 5. Both shell shape and apertural lip thickness contributed to shell strength suggesting that constitutive shell shape development and inducible lip thickening have evolved jointly to form an effective defence in habitats where predation risk is high. PMID- 22320428 TI - Sweet's syndrome masquerading as figurate erythema. PMID- 22320429 TI - Levels and patterns of expression of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, glucose transporter-1 and CD105 in adenoid cystic carcinomas with high-grade transformation. AB - AIMS: To compare the expression of proteins regulated by hypoxia between adenoid cystic carcinoma (ACC) with and without high-grade transformation (HGT). METHODS AND RESULTS: In eight ACC-HGT and 18 ACC without HGT, expression of hypoxia inducible factor-1 (HIF-1alpha), vascular endothelial growth factor (VEGF), glucose transporter-1 (GLUT-1) and microvascular density (MVD) by CD105 (a hypoxia-inducible protein expressed in angiogenic endothelial cells) was determined. Expression levels of HIF-1alpha and VEGF as well as CD105-MVD did not differ significantly between: (i) transformed and conventional areas (TA and CA, respectively) of ACC-HGT, (ii) CA and ordinary ACC. HIF-1alpha was detected in 100% of cases and presented a diffuse expression pattern. No significant association was found between levels of HIF-1alpha expression and tumour size, metastasis and recurrence. GLUT-1 showed a prostromal expression pattern and was observed exclusively in TA (three of six cases) and in only three of 14 ACC. CONCLUSIONS: Both the absence of significant alterations in levels of expression of HIF-1alpha, VEGF and CD105 and the patterns of expression of HIF-1alpha and GLUT-1 suggest that hypoxia may not play a key role in the process of high-grade transformation of ACC. Although HIF-1alpha expression is a common finding in ACC, it cannot be used as a marker of tumour aggressiveness. PMID- 22320430 TI - Dereplication, residual complexity, and rational naming: the case of the Actaea triterpenes. AB - The genus Actaea (including Cimicifuga) has been the source of ~200 cycloartane triterpenes. While they are major bioactive constituents of complementary and alternative medicines, their structural similarity is a major dereplication problem. Moreover, their trivial names seldom indicate the actual structure. This project develops two new tools for Actaea triterpenes that enable rapid dereplication of more than 170 known triterpenes and facilitates elucidation of new compounds. A predictive computational model based on classification binary trees (CBTs) allows in silico determination of the aglycone type. This tool utilizes the Me (1)H NMR chemical shifts and has potential to be applicable to other natural products. Actaea triterpene dereplication is supported by a new systematic naming scheme. A combination of CBTs, (1)H NMR deconvolution, characteristic (1)H NMR signals, and quantitative (1)H NMR (qHNMR) led to the unambiguous identification of minor constituents in residually complex triterpene samples. Utilizing a 1.7 mm cryo-microprobe at 700 MHz, qHNMR enabled characterization of residual complexity at the 10-20 MUg level in a 1-5 mg sample. The identification of five co-occurring minor constituents, belonging to four different triterpene skeleton types, in a repeatedly purified natural product emphasizes the critical need for the evaluation of residual complexity of reference materials, especially when used for biological assessment. PMID- 22320431 TI - Raman-activated cell counting for profiling carbon dioxide fixing microorganisms. AB - Raman microspectroscopy is a label-free and nondestructive technique to measure the intrinsic chemical profile of single cells. The naturally weak Raman signals hampered the application of Raman spectroscopy for high-throughput measurements. Nearly all photosynthetic microorganisms contain carotenoids that are active molecules for resonance Raman at a 532 nm excitation wavelength. Hence, the acquisition time for a single photosynthetic microorganism can be as short as 1 ms. The carotenoid bands in Raman spectra of photosynthetic microorganisms utilizing (13)CO(2) shifted when compared to the spectra of cells utilizing (12)CO(2). Here, a mixture of (12)C- and (13)C-cyanobacterial cells were counted using a microfluidic-device-based Raman-activated cell counting procedure to prove the concept that Raman spectroscopy can be used as a high-throughput method to profile a cell population. PMID- 22320432 TI - Silk self-assembly mechanisms and control from thermodynamics to kinetics. AB - Silkworms and spiders generate fibers that exhibit high strength and extensibility. The underlying mechanisms involved in processing silk proteins into fiber form remain incompletely understood, resulting in the failure to fully recapitulate the remarkable properties of native fibers in vitro from regenerated silk solutions. In the present study, the extensibility and high strength of regenerated silks were achieved by mimicking the natural spinning process. Conformational transitions inside micelles, followed by aggregation of micelles and their stabilization as they relate to the metastable structure of silk are described. Subsequently, the mechanisms to control the formation of nanofibrous structures were elucidated. The results clarify that the self-assembly of silk in aqueous solution is a thermodynamically driven process where kinetics also play a key role. Four key factors, molecular mobility, charge, hydrophilic interactions, and concentration underlie the process. Adjusting these factors can balance nanostructure and conformational composition, and be used to achieve silk-based materials with properties comparable to native fibers. These mechanisms suggest new directions to design silk-based multifunctional materials. PMID- 22320434 TI - Mitral bioprosthesis hypertrophic scaring and native aortic valve fibrosis during benfluorex therapy. AB - The authors describe the case of a simultaneous mitral bioprosthesis hypertrophic scaring and native aortic valve fibrosis during benfluorex therapy in a 40-year old woman. Four years before, she underwent a mitral valve replacement after the diagnosis of mitral regurgitation during benfluorex treatment (150 mg/day). This drug was reintroduced postoperatively. She presented with exercise and sometimes resting dyspnoea. The bioprosthesis and aortic valves exhibited similar histopathological lesions. Thickening and plaque deposits made by smooth muscle alpha actin- and vimentin-positive cells in a glycosaminoglycan matrix were observed. The study discusses the putative contribution of circulating progenitor cells activated by 5-HT(2B) receptor agonists in the development of drug-induced heart disease. PMID- 22320435 TI - A microwell cell culture platform for the aggregation of pancreatic beta-cells. AB - Cell-cell contact between pancreatic beta-cells is important for maintaining survival and normal insulin secretion. Various techniques have been developed to promote cell-cell contact between beta-cells, but a simple yet robust method that affords precise control over three-dimensional (3D) beta-cell cluster size has not been demonstrated. To address this need, we developed a poly(ethylene glycol) (PEG) hydrogel microwell platform using photolithography. This microwell cell culture platform promotes the formation of 3D beta-cell aggregates of defined sizes from 25 to 210 MUm in diameter. Using this platform, mouse insulinoma 6 (MIN6) beta-cells formed aggregates with cell-cell adherin junctions. These naturally formed cell aggregates with controllable sizes can be removed from the microwells for macroencapsulation, implantation, or other biological assays. When removed and subsequently encapsulated in PEG hydrogels, the aggregated cell clusters demonstrated improved cellular viability (>90%) over 7 days in culture, while the beta-cells encapsulated as single cells maintained only 20% viability. Aggregated MIN6 cells also exhibited more than fourfold higher insulin secretion in response to a glucose challenge compared with encapsulated single beta-cells. Further, the cell aggregates stained positively for E-cadherin, indicative of the formation of cell junctions. Using this hydrogel microwell cell-culture method, viable and functional beta-cell aggregates of specific sizes were created, providing a platform from which other biologically relevant questions may be answered. PMID- 22320436 TI - Availability of CBCT and iatrogenic alveolar nerve injuries. AB - OBJECTIVE: To examine whether the rapid increase in the availability of cone-beam computed tomography (CBCT) has changed the number of inferior alveolar nerve (IAN) injuries related to the removal of mandibular third molars in Finland. The hypothesis was that the number of nerve injuries should diminish due to better imaging methods. MATERIALS AND METHODS: The number of CBCT devices, the annual number of CBCT examinations and the number of permanent IAN injuries occurring between 1997 and 2007 were analyzed. The data was collected from three national registers: the Radiation and Nuclear Safety Authority, the Social Insurance Institution and the Patient Insurance Centre. A detailed analysis was made from the cases of permanent IAN injuries. RESULTS: The first CBCT device was registered in 2002 and the cumulative number of these devices in 2009 was 22. There was an increase from 555 to 3160 in the number of annual CBCT examinations during the period 2004-2009. The total number of permanent IAN injuries during the years 1997-2007 was 129 and remained stable throughout the period (regression analysis, p = 0.974, r (2) = 0.01). CONCLUSIONS: Contrary to this hypothesis, the availability of CBCT devices has had no significant influence on the number of IAN injuries related to mandibular third molar removals in Finland. More education should be given to optimize the use of CBCT to cover difficult cases that may give rise to complications. PMID- 22320437 TI - Sustainable seaweed cutting? The rockweed (Ascophyllum nodosum) industry of Maine and the Maritime Provinces. AB - Burgeoning global demand for products derived from seaweeds is driving the increased removal of wild coastal seaweed biomass, an emerging low trophic level industry. These products are marketed as organic and "sustainable." Brown macroalgae, such as kelps (Laminariales) and rockweeds (Fucales), are foundational species that form underwater forests and thus support a diverse vertebrate, invertebrate, and algal community-including important commercial species-and deliver organic matter to coastal ecosystems. The measure of sustainability used by the rockweed (Ascophyllum nodosum (L.) LeJolis) industry, maximum sustainable yield, accounts for neither rockweed's role as habitat for 150+ species, including species of commercial or conservation significance, nor its role in coastal and estuarine ecosystems. To determine whether rockweed cutting is "sustainable" will require data on the long-term and ecosystem-wide impacts of cutting rockweed. Once a sustainable level of cutting is determined, strict regulation by resource managers will be required to protect rockweed habitat. Until sustainable levels of cutting and appropriate regulations are identified, commercial-scale rockweed cutting presents a risk to coastal ecosystems and the human communities that depend on those ecosystems. PMID- 22320438 TI - The mitochondrial genome of the arbuscular mycorrhizal fungus Gigaspora margarita reveals two unsuspected trans-splicing events of group I introns. AB - * Arbuscular mycorrhizal fungi (AMF) are ubiquitous organisms that benefit ecosystems through the establishment of an association with the roots of most plants: the mycorrhizal symbiosis. Despite their ecological importance, however, these fungi have been poorly studied at the genome level. * In this study, total DNA from the AMF Gigaspora margarita was subjected to a combination of 454 and Illumina sequencing, and the resulting reads were used to assemble its mitochondrial genome de novo. This genome was annotated and compared with those of other relatives to better comprehend the evolution of the AMF lineage. * The mitochondrial genome of G. margarita is unique in many ways, exhibiting a large size (97 kbp) and elevated GC content (45%). This genome also harbors molecular events that were previously unknown to occur in fungal mitochondrial genomes, including trans-splicing of group I introns from two different genes coding for the first subunit of the cytochrome oxidase and for the small subunit of the rRNA. * This study reports the second published genome from an AMF organelle, resulting in relevant DNA sequence information from this poorly studied fungal group, and providing new insights into the frequency, origin and evolution of trans-spliced group I introns found across the mitochondrial genomes of distantly related organisms. PMID- 22320439 TI - The relationship of nocturnal melatonin to estradiol and progesterone in depressed and healthy pregnant women. AB - PURPOSE: To assess the relationship between nocturnal plasma melatonin and serum estradiol (E(2)) and progesterone (P(4)) levels in depressed pregnant women (DW) and matched healthy women (HW). METHODS: We used analysis of variance (ANOVA) and linear regression analyses on data obtained from pregnant HW and DW. RESULTS: Log E(2) and log P(4) were positively correlated with measures of melatonin quantity in HW (p<0.05) but not DW, controlling for age. Log E(2) and log P(4) were positively correlated with melatonin offset and duration in DW (p<0.01) but not HW. CONCLUSIONS: Pregnant DW may be less sensitive than HW to modulation of melatonin secretion by E(2) and P(4). That melatonin timing measures are more sensitive to E(2) and P(4) variation in DW may reflect a circadian system more attuned to the need for realignment in DW than in HW. These altered sensitivities to reproductive hormones may reflect a biologic vulnerability that predisposes some pregnant women to depression. PMID- 22320440 TI - Effect of cationic ionophore monensin on the lipid composition and fluidity of rat epididymal spermatozoal membrane. AB - The present study was aimed at exploring the effect of monensin, an antibiotic carboxylic polyether ionophore specific for Na(+), on the structural, chemical, and physiological changes of the epididymal sperm of Wistar rats. Animals received monensin at the dose of 3.5 mg/kg body weight daily orally for 70 days, a treatment duration that corresponds to the spermatogenic cycle in rats. At the end of the treatment regime, three regions of the epididymis were separated and the spermatozoa were collected. The plasma membranes of the spermatozoa were isolated and lipid composition, such total lipid, phospholipid, cholesterol, and ganglioside-sialic acid, was studied. Membrane dynamic behavior was investigated by lipid translational fluidity by pyrene excimer formation and rotational diffusion by diphenyl hexatriene polarization and anisotropy parameter. Structural changes in membrane were also evaluated by the dye-binding study with anilino naphthalene sulphonic acid. The results showed marked changes in lipid compositions, fluidity parameters, and kinetics of fluorescent dye binding in the epididymis, and it can be concluded that monensin, by interfering with normal physiological changes in spermatozoal maturation, may provide the basis of certain molecular intervention in the fertilizing capability of the epididymal spermatozoa and thereby may induce antifertility properties in male rats. PMID- 22320441 TI - Isolation of functional dendritic cells from murine kidneys for immunological characterization. AB - AIM: The kidney is a complex organ, requiring the contributions of multiple cell types to perform its various functions. Within this system the dendritic cell has been demonstrated to play a key role in maintaining the immunological balance of the kidney. In this methods paper we aim to identify the best method for isolating murine renal dendritic cells. METHODS: The efficiency of isolating dendritic cells from enzymatically digested renal parenchyma by density centrifugation, MACS and FACS was compared. RESULTS: Density centrifugation enriched dendritic cells by only approximately two fold. However, MACS and FACS resulted in a much higher purity (80% versus 95% respectively). CONCLUSIONS: Although FACS gave the highest purity, MACS is the optimal method for isolating dendritic cells given cost and time factors. Isolation of a homogeneous population of renal dendritic cells will enable the molecular and functional dissection of these cells in both homeostasis and disease models. PMID- 22320442 TI - Localized hypertrichosis overlying neurofibroma. PMID- 22320443 TI - Is referral to the neuro-oncology MDT safe? AB - INTRODUCTION: Since 2006, National Institute for Health and Clinical Excellence (NICE) guidelines advise referral of any suspected brain tumour to a dedicated neuro-oncology multidisciplinary team (MDT). We investigated two aspects of MDT safety: whether time to operation was delayed and whether brain abscesses were inappropriately referred to the MDT. MATERIAL(S) AND METHODS: We reviewed the notes of 220 consecutive patients referred to our neuro-oncology service before and after implementation of a pre-operative MDT meeting. RESULTS: Median time to operation was similar for patients referred before and after introduction of the MDT (8 days pre-MDT, 9 days post-MDT). There were four abscesses referred via the MDT with a significantly longer median time to operation than in the pre-MDT era (6 days vs. 1 day), although no patient came to any apparent harm as a consequence. No lesion imaged with MRI was misdiagnosed. DISCUSSION: Pre operative MDT does not lengthen time to operation for patients with brain tumour. However, it may delay time to operation for abscesses inadvertently referred via the MDT route. We advocate the use of MRI to minimise the risk of misdiagnosis of cerebral abscesses. PMID- 22320444 TI - Functional outcomes of decompressive hemicraniectomy following malignant middle cerebral artery infarctions: a systematic review. AB - Decompressive hemicraniectomy has been used increasingly in recent years to treat malignant middle cerebral artery territory infarction. This review examines functional outcome data, with the novel analysis of outcomes according to temporal periods post-surgery. Case series data were pooled to determine significant correlates of outcome. Severe disability was frequently the outcome among survivors within one month post-surgery. Time and rehabilitation were later reflected, with fewer deaths and the emergence of mild to moderate disability increasing in prevalence. Mortality and severe disability were consistently more probable with increasing age. Presurgical clinical status in the form of additional cerebral artery involvement and midline shift also correlated with mortality within the 30-day period post-stroke. PMID- 22320445 TI - Doxorubicin-induced activation of NF-kappaB in melanoma cells is abrogated by inhibition of IKKbeta, but not by a novel IKKalpha inhibitor. AB - Drug resistance is arguably the most important challenge in cancer therapy. Here, doxorubicin induced profound of NF-kappaB activation in melanoma cells with a maximum (3.5-fold) at concentrations relevant in vivo. This was followed by transcriptional induction of several gene products involved in tumor progression. A novel IKKalpha inhibitor (BAY32-5915) was identified and characterized, and doxorubicin-induced NF-kappaB activation was assessed following inhibition of IKKalpha or IKKbeta by small-molecular compounds. While the IKKalpha inhibitor did not affect doxorubicin-induced NF-kappaB activation, this process was completely abrogated when the IKKbeta inhibitor, KINK-1, was used. Moreover, inhibition of IKKbeta, but not IKKalpha, led to significantly increased apoptosis in response to doxorubicin. Our results indicate that the net outcome of chemotherapy is difficult to predict and may even involve mechanisms conferring chemoresistance. In case of doxorubicin-induced NF-kappaB activation, blocking IKKbeta, but not IKKalpha, by small molecules can antagonize this activity and, thus, increase chemosensitivity. PMID- 22320446 TI - Accumulation of p62/SQSTM1 is associated with poor prognosis in patients with lung adenocarcinoma. AB - p62/SQSTM1 is a selective substrate of autophagy, and aberrant accumulation of p62 has been observed in various pathological conditions. To understand the roles p62 plays in non-small-cell lung cancer (NSCLC), we carried out immunohistochemical analyses of p62 expression in a cohort of patients with annotated clinicopathological data. As analyses of murine and human hepatocellular carcinomas suggested a correlation between p62 and Nrf2 accumulations, we also examined NRF2 expression in the same cohort. The expression of NRF2 and p62 was examined by immunohistochemical methods in 109 NSCLC cases, which included patients with adenocarcinoma (n = 72), squamous cell carcinoma (n = 31), and large cell carcinoma (n = 6). Accumulation of NRF2 and p62 was detected in 34% and 37% of NSCLC patients, respectively. The accumulations of p62 and NRF2 did not correlate with each other, but both were associated with worse lung cancer-specific survival (P = 0.0003 for NRF2; P = 0.0130 for p62). NRF2 status had an impact on NSCLC prognosis irrespective of histology types, but p62 status did so particularly in adenocarcinoma (P = 0.037). Multivariate analysis indicated that positive immunoreactivities of NRF2 and p62 were both independent factors predicting worse lung cancer-specific survival (P < 0.0001 for NRF2 and P = 0.04 for p62). This study revealed that both NRF2 and p62 are independent prognostic factors for NSCLC. The prognostic impact of p62 status was pronounced in adenocarcinoma patients, suggesting that molecular mechanisms underlying cancer evolution differ between adenocarcinoma and squamous cell carcinoma. PMID- 22320447 TI - Commentary: Replication, replication, replication: the continued need to substantiate GxE effects in child psychopathology--a response to Laucht et al. (2012). PMID- 22320448 TI - Phylogeography of a Tertiary relict plant, Meconopsis cambrica (Papaveraceae), implies the existence of northern refugia for a temperate herb. AB - The perennial herb Meconopsis cambrica, a western European endemic, is the only European species of the otherwise Himalayan genus Meconopsis and has been interpreted as a Tertiary relict species. Using rbcL and ITS sequence variation, we date the split between M. cambrica and its sister clade Papaver s.str. to the Middle to Upper Miocene (12.8 Myr, 6.4-19.2 Myr HPD). Within M. cambrica, cpDNA sequence variation reveals the existence of two groups of populations with a comparable level of genetic variation: a northern group from Great Britain, the Massif Central, the western Pyrenees and the Iberian System, and a southern group from the central and eastern Pyrenees. Populations from the Cantabrian Mountains were placed in both groups. Based on ITS sequence variation, the divergence between these two groups can be dated to 1.5 Myr (0.4-2.8 Myr HPD), and the age of the British populations is estimated as 0.37 Myr (0.0-0.9 Myr HPD). Amplified fragment length polymorphism results confirm the distinctive nature of the populations from Britain, the Massif Central and the central and eastern Pyrenees. These patterns of latitudinal variation of M. cambrica differ from patterns of longitudinal differentiation found in many other temperate species and imply glacial survival of the northern populations in northerly refugia. The primary differentiation into northern and southern cpDNA groups dates to near the onset of the Quaternary and suggests that an ancient phylogeographic pattern has survived through several glacial periods. Our data provide evidence that the species has persisted for a long period with a highly fragmented and probably very localized distribution. PMID- 22320449 TI - Cost-effectiveness analysis of early versus non-early intervention in acute migraine based on evidence from the 'Act when Mild' study. AB - BACKGROUND: In spite of the important progress made in the abortive treatment of acute migraine episodes since the introduction of triptans, reduction of pain and associated symptoms is in many cases still not as effective nor as fast as would be desirable. Recent research pays more attention to the timing of the treatment, and taking triptans early in the course of an attack when pain is still mild has been found more efficacious than the usual strategy of waiting for the attack to develop to a higher pain intensity level. OBJECTIVE: To investigate the cost effectiveness of early versus non-early intervention with almotriptan in acute migraine. METHODS: An economic evaluation was conducted from the perspectives of French society and the French public health system based on patient-level data collected in the AwM (Act when Mild) study, a placebo-controlled trial that compared the response to early and non-early treatment of acute migraine with almotriptan. Incremental cost-effectiveness ratios (ICERs) were determined in terms of QALYs, migraine hours and productive time lost. Costs were expressed in Euros (year 2010 values). Bootstrapping was used to derive cost-effectiveness acceptability curves. RESULTS: Early treatment has shown to lead to shorter attack duration, less productive time lost, better quality of life, and is, with 92% probability, overall cost saving from a societal point of view. In terms of drug costs only, however, non-early treatment is less expensive. From the public health system perspective, the (bootstrap) mean ICER of early treatment amounts to ?0.38 per migraine hour avoided, ?1.29 per hour of productive time lost avoided, and ?14,296 per QALY gained. Considering willingness-to-pay values of approximately ?1 to avoid an hour of migraine, ?10 to avoid the loss of a productive hour, or ?30,000 to gain one QALY, the approximate probability that early treatment is cost effective is 90%, 90% and 70%, respectively. These results remain robust in different scenarios for the major elements of the economic evaluation. CONCLUSIONS: Compared with non-early treatment, a strategy of early treatment of acute migraine with almotriptan when pain is still mild is, with high probability, cost saving from the French societal perspective and can be considered cost effective from the public health system point of view. PMID- 22320450 TI - Interferon-alpha modulates the chemosensitivity of CD133-expressing pancreatic cancer cells to gemcitabine. AB - Pancreatic cancer is a lethal disease as current chemotherapies with gemcitabine (GEM) are still insufficient. Accumulating evidence suggests that cancer stem cells (CSC) are responsible for chemoresistance and that CD133 is one of the CSC markers in pancreatic cancer. Interferon-alpha (IFN-alpha), a cytokine with pleiotropic effects, has direct cytotoxic and cytostatic effects on tumor cells. The aim of the present study was to investigate whether IFN-alpha can modulate the chemosensitivity of a human pancreatic cancer cell line, Capan-1, to GEM. Cell cycles were evaluated for response to GEM with and without IFN-alpha by BrdU assay. GEM inhibited Capan-1 cell growth in a dose-dependent manner. GEM (IC(50); 100 ng/mL) treatment reduced the number of both CD133(+) and CD133(-) cells in the S phase, induced apoptosis of CD133(-) cells more than that of CD133(+) cells and increased accumulation of CD133(+) cells into the G0/G1 phase. These results infer that CD133(+) cells take shelter into the G0/G1 phase from GEM treatment. IFN-alpha modulated CD133(+) cells from the G0/G1 phase to the S phase. Consequently, apoptosis was accelerated in both CD133(+) and CD133(-) cells after IFN-alpha combined with GEM treatment. Furthermore, GEM combined with IFN-alpha treatment showed a significant tumor suppressive effect in the in vivo study. Importantly, CD133(+) cells showed CSC-like properties, such as generation of spheres, highly invasive ability and high tumorigenesis. These results suggest that IFN-alpha, as a modulator, could contribute to the treatment of CD133(+) cancer cells and be effective in combined chemotherapies with GEM for pancreatic cancer stem-like cells. PMID- 22320451 TI - Rotigotine transdermal patch for the treatment of Parkinson's Disease. AB - Rotigotine, a non-ergot dopamine agonist, has been developed as a novel transdermal formulation. The rotigotine transdermal patch has received EMEA marketing authorization for the treatment of adult patients with early or advanced Parkinson's disease (PD) or with moderate to severe restless legs syndrome (RLS). FDA originally granted a marketing authorization for early PD, which was later suspended, and is now studying the authorization for RLS. The aim of this review is to review the pharmacokinetics, pharmacodynamics as well as the clinical efficacy and tolerability of the rotigotine transdermal patch in PD. Source material was identified using a PubMed search for the term 'rotigotine' and PD. Articles published up to January 2011 or abstract submitted to most relevant international neurology congresses were reviewed. The rotigotine transdermal patch is efficacious for the treatment of PD. Tolerability profile appears to be well within the range of that observed with other non-ergot dopamine agonists in PD. Application-site reactions were the most frequent adverse event, and they were considered mild to moderate in the majority of cases. The rotigotine transdermal patch offers a safe and efficacious alternative for the treatment of PD. Further studies should focus on the possibility that continuous dopamine stimulation by means of the transdermal patch has any influence on levodopa-related motor complications. PMID- 22320452 TI - The ancillary protein 1 of Streptococcus pyogenes FCT-1 pili mediates cell adhesion and biofilm formation through heterophilic as well as homophilic interactions. AB - Gram-positive pili are known to play a role in bacterial adhesion to epithelial cells and in the formation of biofilm microbial communities. In the present study we undertook the functional characterization of the pilus ancillary protein 1 (AP1_M6) from Streptococcus pyogenes isolates expressing the FCT-1 pilus variant, known to be strong biofilm formers. Cell binding and biofilm formation assays using S. pyogenes in-frame deletion mutants, Lactococcus expressing heterologous FCT-1 pili and purified recombinant AP1_M6, indicated that this pilin is a strong cell adhesin that is also involved in bacterial biofilm formation. Moreover, we show that AP1_M6 establishes homophilic interactions that mediate inter-bacterial contact, possibly promoting bacterial colonization of target epithelial cells in the form of three-dimensional microcolonies. Finally, AP1_M6 knockout mutants were less virulent in mice, indicating that this protein is also implicated in GAS systemic infection. PMID- 22320454 TI - Conformers, infrared spectrum and UV-induced photochemistry of matrix-isolated furfuryl alcohol. AB - The infrared spectra of furfuryl alcohol (2-furanmethanol, FFA) were investigated for FFA monomers isolated in low-temperature argon matrices. The structural interpretation of the obtained experimental spectra was assisted by analysis of the molecule's conformational landscape. According to the DFT(B3LYP)/6 311++G(d,p) calculations, five different minimum energy structures were found on the potential energy surface of the molecule. They can be defined by the orientation of the OCCO and CCOH dihedral angles: GG', GG, TG, TT, GT (G = +gauche, G' = -gauche, T = trans) and have a symmetry equivalent configuration: GG' = G'G, GG = G'G', TG = TG', GT = G'T. When zero-point energies are taken into account, only three (GG', GG, and TT) out of the five unique minima correspond to stable structures. The most stable conformer GG' (OCCO, 72.7 degrees ; CCOH, 59.3 degrees ), which in gas phase at room temperature accounts for ~65% of the total population, was the only form isolated in the argon matrices at 14 K. The other two relevant forms convert into conformer GG' during matrix deposition. The low temperature glassy and crystalline states of FFA were also obtained and their infrared spectra assigned, suggesting the sole existence of the GG' conformer also in these phases. The photochemical behavior of FFA induced in situ, by tunable UV-laser, was also studied. The longest wavelength resulting in photochemical changes in the structure of the irradiated sample was found to be lambda = 229 nm. Such UV irradiation of the matrix-isolated FFA led to production of formaldehyde and different isomeric C(4)H(4)O species. Cycloprop-2-ene-1 carbaldehyde and buta-2,3-dienal (two conformers) are the main initial C(4)H(4)O photoproducts formed upon short-time excitation at lambda = 229 nm. But-3-ynal (two conformers) was the principal photoproduct resulting from prolonged excitation at lambda= 229 nm, being consumed upon irradiation at shorter wavelengths (lambda < 227.5 nm). Vinyl ketene is produced from FFA in the trans conformation and undergoes isomerization to the cis form upon irradiation at lambda < 227.5 nm. Cyclopropene, propyne, allene, and CO were also identified in the irradiated matrices (in particular at the later stages of irradiation), suggesting that the photoproduced aldehydes partially decarbonylate during the performed photochemical experiments. PMID- 22320455 TI - Microarray analysis of gastric mucosa among children with Helicobacter pylori infection. AB - BACKGROUND: Although initial infection with Helicobacter pylori may occur before 5 years of age, the pediatric mucosal immune response against H. pylori is not clear. The aim of the present study was to evaluate immune responses in the H. pylori-infected gastric mucosa of children using microarray and real-time polymerase chain reaction (PCR) analysis of pediatric gastric samples. METHODS: Gastric samples were obtained from 12 patients undergoing routine endoscopy of chronic abdominal complaints. Six patients (three boys, three girls) aged 10.1 14.6 years had evidence of H. pylori infection, and the remaining six (three boys, three girls) aged 10.3-15.5 years had no evidence of infection and presented no histological changes associated with gastritis. Microarray and real time PCR analyses were performed, and the changes in gene expression-related immune response were also analyzed. RESULTS: Using microarray analysis, the total number of significantly upregulated and downregulated genes (fold change >5, P < 0.01) was 21 in the antrum and 16 in the corpus when comparing patients with or without infection. Using real-time PCR, the expression of lipocalin-2 (Lcn2), C-C motif chemokine ligand (CCL) 18, C-X-C motif chemokine ligand (CXCL) 9 and CXCL11 was upregulated, while the expression of pepsinogen (PG) I and PGII was downregulated when comparing patients with or without infection. CONCLUSIONS: Lcn2, CCL18, CXCL9, CXCL11, PGI and PGII play important roles in childhood H. pylori infection. PMID- 22320456 TI - A new perspective on the incentive-blood donation relationship: partnership, congruency, and affirmation of competence. AB - BACKGROUND: The Motivation Crowding-out Theory suggests that incentives undermine intrinsic motivation and thus blood donation behavior. While there is strong evidence showing the negative relationship between monetary incentives and blood donation, findings on the effect of nonmonetary incentives are mixed. Set in a voluntary, nonremunerated environment, this study explores aspects of the nonmonetary incentive-blood donation relationship not captured by the crowding out hypothesis. STUDY DESIGN AND METHODS: In-depth interviews were conducted to explore donors' attitudes toward nonmonetary incentives currently used or considered by the Australian Red Cross Blood Service (Blood Service). Transcripts were analyzed using an inductive, thematic approach. RESULTS: Of the nonmonetary incentives examined (i.e., health screening tests, branded tokens, paid time off work, recognition of key milestones, and postdonation refreshments), none were found to crowd out intrinsic motivation, although not all were viewed favorably. Donors who viewed branded tokens negatively considered the cost implications for the Blood Service, while donors who responded positively considered the public benefit of tokens in raising the profile of the Blood Service. Other nonmonetary incentives-paid time off work, postdonation refreshments, and health screening tests-were viewed positively because donors perceived them to be congruent to the effort expended in donating blood. Finally, donors expressed a preference for private over public recognition when acknowledging significant contributions. CONCLUSION: When operating in a voluntary, nonremunerated environment, blood services should view donors as supply partners rather than customers, only consider nonmonetary incentives that are congruent with the act of donation, and provide private rather than public recognition of key milestones. PMID- 22320659 TI - European Academy of Childhood Disability (EACD): Recommendations on the definition, diagnosis and intervention of developmental coordination disorder (pocket version). German-Swiss interdisciplinary clinical practice guideline S3 standard according to the Association of the Scientific Medical Societies in Germany. Pocket version. Definition, diagnosis, assessment, and intervention of developmental coordination disorder (DCD). PMID- 22320660 TI - Selecting the particle size distribution for drugs with low water solubility - mathematical model. AB - PURPOSE: To introduce guidelines in selecting the particle size distribution (n(0), cm(-1)) that will guarantee optimal oral absorption for drugs with low solubility. METHODS: Unlike other multi-compartmental models the gastrointestinal tract is modeled as a continuous tube with spatially varying properties. The transport through the intestinal lumen is described using the dispersion model. The model accounts for the dissolution of poly-dispersed powders. RESULTS: The model was used to examine the sensitivity of the absorption on permeability (P) and water solubility (C(s)) following administration in different log-normal powders. The absorption exhibits inverse sigmoidal dependence on the mean particle size (r(m), um) regardless of the administrated dose or drug properties. Thus, there is an optimal r(m) that maximizes the benefit-cost ratio of the formulation; finer particles do not improve the absorption while coarser particles decrease it. Using the model we find that the optimal r(m) depends mainly on the drug C(s) and on the geometrical standard deviation (gSTD). CONCLUSIONS: The results of this work provide the formulator with guidelines to select both r(m) and gSTD that guarantee optimal absorption. PMID- 22320661 TI - Synthesis of triptycene-derived macrotricyclic host containing two dibenzo-[18] crown-6 moieties and its complexation with paraquat derivatives: Li(+)-ion controlled binding and release of the guests in the complexes. AB - A new triptycene-derived macrotricyclic host containing two dibenzo-[18]-crown-6 moieties was synthesized and shown to form 1:1 complexes with paraquat derivatives in solution, in which the guests all thread the central cavity of the host. However, it was interestingly found that, depending on the paraquat derivatives with different functional groups, the host can form stable 1:1 or 1:2 complexes in different complexation modes in the solid state, which is significantly different from those of the macrotricyclic host containing two dibenzo-[24]-crown-8 moieties. The formation of the complexes was also proved by the ESI MS and electrochemical experiments. Moreover, it was found that the binding and release of the guests in the complexes could be easily controlled by the addition and removal of lithium ions. PMID- 22320662 TI - Cu(I) affinities of the domain 1 and 3 sites in the human metallochaperone for Cu,Zn-superoxide dismutase. AB - The delivery of copper by the human metallochaperone CCS is a key step in the activation of Cu,Zn-superoxide dismutase (SOD1). CCS is a three-domain protein with Cu(I)-binding CXXC and CXC motifs in domains 1 and 3, respectively. A detailed analysis of the binding of copper to CCS, including variants in which the Cys residues from domains 1 and 3 have been mutated to Ser, and also using separate domain 1 and 3 constructs, demonstrates that CCS is able to bind 1 equiv of Cu(I) in both of these domains. The Cu(I) affinity of domain 1 is approximately 5 * 10(17) M(-1) at pH 7.5, while that of domain 3 is at least 1 order of magnitude weaker. The CXXC site will therefore be preferentially loaded with Cu(I), suggesting that domain 1 plays a role in the acquisition of the metal. The delivery of copper to the target occurs via domain 3 whose structural flexibility and ability to be transiently metalated during copper delivery appear to be more important than the Cu(I) affinity of its CXC motif. The Cu(I) affinity of domain 1 of CCS is comparable to that of HAH1, another cytosolic copper metallochaperone. CCS and HAH1 readily exchange Cu(I), providing a mechanism whereby cross-talk can occur between copper trafficking pathways. PMID- 22320663 TI - Optimisation and validation of a quantitative and confirmatory method for residues of macrolide antibiotics and lincomycin in kidney by liquid chromatography coupled to mass spectrometry. AB - A solid phase extraction followed by a liquid chromatography (LC)-tandem mass spectrometry (MS/MS) detection method for the confirmatory analysis of lincomycin (LIN), clindamycin (CLI), tilmicosin (TIM), erythromycin (ERI) and tylosin (TYL) residues in kidney were optimised and validated for monitoring and controlling the use of these antibiotics in food producing-animals. The method optimisation was carried out by testing changes in the extraction buffer pH and in the ammonium/acetonitrile concentrations on SPE eluent solutions. The optimised extraction procedure involved the extraction of the analytes with a pH 8 phosphate buffer, clean-up on a reversed-phase mixed-cation exchange cartridge, followed by the elution of the analytes in a 98:2 acetonitrile/ammonia solution, concentration in air flow and re-dissolved with an 1:1 methanol/water solution. The analytes were detected in an LC-MS/MS system in electrospray positive ionisation mode. The validation was performed according to the European Commission Decision 2002/657/EC. Linearity was established for all analytes using the method of least weighted squares and CCalpha values ranged from 5.3% to 21.1% higher than the minimum residue limit (MRL) values. The addition levels varied from 0.5 to 1.50 MRL for all analytes, with recoveries exceeding 92.5%. The relative standard deviations (RSD%) in terms of repeatability (n = 54) and reproducibility (n = 108) for all analytes were less than 21.6% and 21.4%, respectively. The uncertainties were calculated by simplified methods using the calibration curve uncertainty and the intermediate precision to obtain the combined measurement uncertainty. The results of the validation process demonstrated that this method is suitable for the quantification and confirmation of antibiotic residues for the Brazilian Residue and Contaminant Control Plan (PNCR). PMID- 22320664 TI - Assessing the continuum of event-based biosurveillance through an operational lens. AB - This research follows the Updated Guidelines for Evaluating Public Health Surveillance Systems, Recommendations from the Guidelines Working Group, published by the Centers for Disease Control and Prevention nearly a decade ago. Since then, models have been developed and complex systems have evolved with a breadth of disparate data to detect or forecast chemical, biological, and radiological events that have a significant impact on the One Health landscape. How the attributes identified in 2001 relate to the new range of event-based biosurveillance technologies is unclear. This article frames the continuum of event-based biosurveillance systems (that fuse media reports from the internet), models (ie, computational that forecast disease occurrence), and constructs (ie, descriptive analytical reports) through an operational lens (ie, aspects and attributes associated with operational considerations in the development, testing, and validation of the event-based biosurveillance methods and models and their use in an operational environment). A workshop was held in 2010 to scientifically identify, develop, and vet a set of attributes for event-based biosurveillance. Subject matter experts were invited from 7 federal government agencies and 6 different academic institutions pursuing research in biosurveillance event detection. We describe 8 attribute families for the characterization of event-based biosurveillance: event, readiness, operational aspects, geographic coverage, population coverage, input data, output, and cost. Ultimately, the analyses provide a framework from which the broad scope, complexity, and relevant issues germane to event-based biosurveillance useful in an operational environment can be characterized. PMID- 22320665 TI - Sodium metabisulfite as a contact allergen--an example of a rare chemical mechanism for protein modification. AB - BACKGROUND: Skin-sensitizing chemicals that cause allergic contact dermatitis do so by reacting with self-proteins such that the modified structure becomes antigenic. The reaction chemistry involved is well characterized, but there are exceptions, such as the occasional allergen sodium metabisulfite. OBJECTIVES: To identify the potential in cutaneo reaction chemistry of sodium metabisulfite. METHODS: The established protein reaction chemistry associated with aqueous sulfite chemistry was explored in the context of the protein modification stage in allergic contact dermatitis. RESULTS: A probable mechanism for the in cutaneo modification of proteins by sodium metabisulfite involves the sulfite di-anion, acting as a nucleophile towards electrophilic centres in proteins, which is a rare mechanism, as most known skin-sensitizing chemicals behave as electrophiles. CONCLUSIONS: Sodium metabisulfite is an unusual but not infrequent contact allergen whose chemistry suggests a previously unrecognized protein modification mechanism involving nucleophilic attack by sulfite di-anions on target electrophilic centres in skin proteins. The chemical properties required for sensitization by nucleophilic attack on skin proteins are quite restrictive, so the domain of nucleophilic sensitizers is expected to be small. Thiourea derivatives are among the sensitizers likely to act by this mechanism. PMID- 22320666 TI - Contact allergy to sodium sulfite and its relationship to sodium metabisulfite. AB - BACKGROUND: Sulfites are in widespread use as preservatives/antioxidants. There is increasing recognition of allergic contact dermatitis caused by sodium metabisulfite; however, contact allergy to sodium sulfite is less well recognized. OBJECTIVES: We sought to establish the prevalence of positive patch test reactions to sodium sulfite in our patient population and investigate its relationship with sodium metabisulfite. METHODS: Over a 4-month period, 183 patients referred for patch testing were tested with sodium sulfite 1% pet. in addition to sodium metabisulfite 1% pet., which already forms part of our baseline series. RESULTS: Positive allergic reactions occurred to sodium metabisulfite in 5.5% of the tested patients and to sodium sulfite in 3.8% of the tested patients. Sixty per cent of patients with a positive reaction to sodium metabisulfite were positive to sodium sulfite. Only 1 patient (0.6%) with a negative reaction to sodium metabisulfite showed a positive reaction to sodium sulfite. CONCLUSIONS: This study shows that the majority of patients with positive reactions to sodium metabisulfite are also positive to sodium sulphite. Routinely patch testing with sodium sulfite is probably unnecessary, as most patients with positive reactions will also react to sodium metabisulfite. Clinicians should consider advising patients to avoid sodium sulfite and other sulfites when a positive allergic reaction to sodium metabisulfite occurs. PMID- 22320667 TI - Patch test concentrations (doses in mg/cm2 ) for the 12 non-mix fragrance substances regulated by European legislation. AB - BACKGROUND: According to EU legislation, 26 fragrance substance allergens must be labelled on cosmetic products. For 12 of them, the optimal patch test concentration/dose has not been evaluated. OBJECTIVES: To establish the optimal patch test doses in mg/cm2 for the 12 fragrance substances that are not included in fragrance mix I or II in the European baseline patch test series. MATERIALS AND METHODS: Patch testing with the 12 fragrance substances was performed in a stepwise manner encompassing up to five rounds in at least 100 dermatitis patients for each round. Before patch testing, an individual maximum concentration/dose was determined for each fragrance substance. RESULTS: The predetermined maximum patch test concentrations/doses could be tested for all 12 fragrance substances, with no observable adverse reactions being noted. CONCLUSIONS: For each fragrance substance investigated, it is recommended that half of the maximum patch test dose (mg/cm2) be used for aimed and screening patch testing. PMID- 22320668 TI - A pilot study aimed at finding a suitable eugenol concentration for a leave-on product for use in a repeated open application test. AB - BACKGROUND: Knowledge of sensitization and elicitation thresholds and the time dose relationship for elicitation of contact dermatitis is important in order to provide safe products for consumers. OBJECTIVE: Since previous studies performed with eugenol had showed negative results in a repeat open application study (ROAT) study, we wanted to perform a ROAT with higher concentration (maximum allowed) and longer ROAT. MATERIALS: 5 volunteers previously tested positive to eugenol were studied. They performed a ROAT test for maximum 4 weeks with four different solutions. Results. Four of five reacted to the maximum concentration of eugenol in the ROAT. CONCLUSION: In patients sensitized to eugenol, with the maximum allowed concentration of eugenol and given a prolonged ROAT (4 weeks), there is a clear risk of elicitating an allergic contact dermatitis. PMID- 22320669 TI - The detection of clinically relevant contact allergens with a standard screening tray of 28 allergens. AB - BACKGROUND: A standard method for diagnosing allergic contact dermatitis in the United States is the thin-layer rapid use epicutaneous (TRUE) test (TRUE TestTM), which consists of three panels containing 20 individual allergens and eight allergen mixes. Previous studies had raised concern regarding the adequacy of the initial two-panel TRUE TestTM system (16 individual allergens and seven allergen mixes) in fully assessing patients with possible allergic contact dermatitis. OBJECTIVES: We sought to investigate the effectiveness of the current three-panel TRUE TestTM as the sole diagnostic tool for detecting allergic contact dermatitis. PATIENTS/MATERIALS/METHODS: This study was a retrospective analysis of 2088 patients who underwent patch testing between 1995 and 2010. Study groups were analysed to determine whether positive reactions were to allergens and/or mixes present in the TRUE TestTM panels. RESULTS: Of the 2088 patch-tested patients, 1385 had at least one positive reaction. Among these 1385 patients, 27.6% were fully evaluated by use of only the TRUE TestTM series, 49.9% were partially evaluated, and 22.5% did not have any of their allergens detected. On assessment for clinical relevance, similar percentages were observed. CONCLUSION: In our study, the current TRUE TestTM series of 28 allergens would have completely identified allergens in only 27.6% of patients. Broadening the standard panel to include common allergens causing >50% of allergic contact dermatitis cases in a given geographical location and aim testing allergens on the basis of the patient's history will increase the test's sensitivity. PMID- 22320670 TI - Allergic contact dermatitis caused by the emulsifier triceteareth-4-phosphate. PMID- 22320671 TI - Allergic contact dermatitis caused by dexpanthenol: report of two cases. PMID- 22320672 TI - Allergic contact dermatitis to colophonium in a sanitary pad-an overlooked allergen? PMID- 22320673 TI - The reliability of visual scoring of patch test reactions revisited. PMID- 22320674 TI - Temporomandibular disorders after orthognathic surgery in patients with mandibular prognathism with depression as a risk factor. AB - OBJECTIVE: To examine the prevalence of temporomandibular disorders (TMD) after orthodontic-surgical treatment in patients with mandibular prognathism and analyze psychosocial variables related to TMD. MATERIALS AND METHODS: The case control study comprised 40 patients with mandibular prognathism who underwent combined orthodontic-surgical treatment (orthognathic surgery group). Forty-two patients with untreated mandibular prognathism served as a control group. Research diagnostic criteria for temporomandibular disorders was used in order to assess the clinical diagnosis of TMD (Axis I) and to estimate depression, somatization and patient's disability related to chronic pain (Axis II). RESULTS: The overall prevalence of TMD was not significantly different between the groups. Myofascial pain was significantly higher, while arthralgia, arthritis and arthrosis was significantly lower in the orthognathic group compared with the controls (90.5% vs 50.0%, 0.0% vs 27.8%, respectively) (p < 0.05). Females in orthognathic surgery group showed higher prevalence of TMD (p < 0.05) and myofascial pain (p < 0.01) and increased level of chronic pain (p < 0.05) in comparison with post-operative males. No significant difference in chronic pain, somatization and depression scores was found between investigated groups. With respect to presence of TMD within the groups depression was higher in untreated subjects with dysfunction (p < 0.05). CONCLUSION: Prevalence of TMD immediately after completion of orthodontic-surgical treatment for mandibular prognathism is similar to frequency of dysfunction in untreated subjects, is significantly higher in females and is most commonly myogenic. Furthermore, females show an increased level of chronic pain post-operatively. Somatization and depression levels do not differ between patients with corrected prognathism and untreated prognathic patients. PMID- 22320675 TI - Characterization of a new allele: HLA-A*03:134. AB - The new A*03:134 differs from A*03:01:01:01 by one amino acid change at codon 264. PMID- 22320676 TI - Inhibition of FAK prevents blister formation in the neonatal mouse model of pemphigus vulgaris. AB - Pemphigus vulgaris (PV) is an autoimmune blistering skin disease characterized by suprabasal acantholysis and by autoantibodies against desmoglein 3 localized on desmosomes. In addition, caspases also seem to participate in this blistering disease. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase involved in cytoskeleton remodelling and formation and disassembly of cell adhesion structures. We have previously demonstrated that HER (human epidermal growth factor receptor related) isoforms, Src (Rous sarcoma) and mammalian target of rapamycin (mTOR), three molecules implicated in signalling processes, take part in suprabasal acantholysis and apoptosis induced by PV-IgG in a mouse model. Our aim was to investigate whether upregulation of FAK is implicated in the development of PV lesions. Herein, using a mouse model, PV-IgG administration showed an increased level of FAK phosphorylated on 397 and 925 tyrosine residues in the basal layer of epidermis. When mice were pretreated with a FAK inhibitor (FI), the acantholysis of the basal layer of epidermis was absent. More interestingly, we observed that phosphorylated FAK (Y397/925) decreased when HER isoforms, Src, mTOR and pan-caspases inhibitors were employed before PV-IgG administration. In addition, pretreatment with the FI before PV-IgG injection prevented the changes in both Bax and Bcl-2 expression and caspase-9 and caspase 3 activities induced by PV-IgG. Finally, FI reduced the expression of phosphorylated Src and mTOR in the basal cells of epidermis. In conclusion, our data reveal a novel role of phosphorylated FAK (Y397/925) in PV development involving HER isoforms, Src and mTOR kinases. PMID- 22320677 TI - An unusual presentation of anti-Hu-associated paraneoplastic limbic encephalitis. AB - Paraneoplastic limbic encephalitis is a rare disorder characterized by personality changes, seizures, memory loss, and psychiatric symptoms often associated with antineuronal antibodies. It is well described in the adult literature but is still underreported in the pediatric literature. Symptoms are usually multifocal and subacute in presentation, occurring over days to weeks; however, in rare cases, symptom onset can be more gradual. We report the case of a 9-year-old male with anti-Hu-associated paraneoplastic limbic encephalitis that presented as episodic ataxia and behavioral changes evolving to intractable epilepsy and worsening behavioral changes over the course of a year. This case highlights the importance of considering a paraneoplastic disorder in the differential diagnosis for unexplained multifocal neurological symptoms of subacute or chronic onset as earlier detection and treatment may result in an improved outcome. PMID- 22320679 TI - Tumor-suppressive microRNA silenced by tumor-specific DNA hypermethylation in cancer cells. AB - MicroRNA (miRNA) genes, located in intergenic or intragenic non-coding regions of the genome, are transcribed and processed to small non-protein-coding RNA of approximately 22 nucleotides negatively regulating gene expression. Some miRNA have already been reported for their genetic alterations, aberrant expression and oncogenic or tumor-suppressive functions. After 2008, there has been a striking increase in the number of publications reporting tumor-suppressive miRNA (TS miRNA) silenced epigenetically in various types of cancers, suggesting important clinical applications for miRNA-based molecular diagnosis and therapy for cancers. Here, we introduce a correlation of the gene silencing of TS-miRNA through CpG island hypermethylation with the genomic distances between intergenic and intragenic miRNA genes or protein-coding host genes and CpG islands located around these genes. Furthermore, we also discuss the potential of miRNA replacement therapy for cancers using double-stranded RNA mimicking TS-miRNA. PMID- 22320680 TI - Paraneoplastic erythema annulare centrifugum eruption: PEACE. AB - Erythema annulare centrifugum is a reactive erythema of various possible etiologies including, although less often, an associated cancer. Cancer-related erythema annulare centrifugum is most commonly associated with lymphoproliferative malignancies, specifically lymphoma and leukemia. Malignancy associated erythema annulare centrifugum is more frequently seen in women than men and the presence of skin lesions usually precedes the clinical diagnosis of the underlying malignancy. Neoplasm-derived erythema annulare centrifugum lesions often resolve following treatment of the cancer. Recurrence of erythema annulare centrifugum may occur along with the relapse of the underlying malignancy. Paraneoplastic erythema annulare centrifugum eruption (PEACE) is speculated to be a result of a cytokine or other tumor-associated factors. PMID- 22320681 TI - Primary hepatocellular carcinoma of the pancreas: a case report and review of the heterogeneous group of pancreatic hepatoid carcinomas. PMID- 22320682 TI - Platelet concentrates prepared after a 20- to 24-hour hold of the whole blood at 22 degrees C. AB - BACKGROUND: The Food and Drug Administration (FDA) requires that red blood cells must be refrigerated within 8 hours of whole blood collection. Longer storage of whole blood at 22 degrees C before component preparation would have many advantages. STUDY DESIGN AND METHODS: Two methods of holding whole blood for 20 to 24 hours at room temperature were evaluated, refrigerated plates or a 23 degrees C incubator. After extended whole blood storage, platelet (PLT) concentrates were prepared from PLT-rich plasma on Day 1 postdonation, and the PLTs were stored for 6 more days. On Day 7 of PLT storage, blood was drawn from each subject to prepare fresh PLTs. The stored and fresh PLTs were radiolabeled and transfused into their donor. RESULTS: Eleven subjects' whole blood was stored using refrigerated butanediol plates (Compocool, Fresenius), and 10 using an incubator. Poststorage PLT recoveries averaged 47 +/- 13% versus 53 +/- 11% and survivals averaged 4.6 +/- 1.7 days versus 4.7 +/- 0.9 days for Compocool versus incubator storage, respectively (p = NS). With all results, poststorage PLT recoveries averaged 75 +/- 10% of fresh and survivals 57 +/- 13% of fresh; PLT recoveries met FDA guidelines for poststorage PLT viability but not survivals. CONCLUSION: Seven-day poststorage PLT viability is comparable when whole blood is stored for 22 +/- 2 hours at 22 degrees C using either refrigerated plates or an incubator to maintain temperature before preparing PLT concentrates. PMID- 22320683 TI - Brain metastases after definitive concurrent chemoradiotherapy in patients with stage III lung adenocarcinoma: carcinoembryonic antigen as a potential predictive factor. AB - The predictive factors for the development of brain metastases in patients with stage III non-small-cell lung cancer receiving concurrent chemoradiotherapy remain unclear. Several studies have suggested adenocarcinoma as a predictive factor of brain relapses. In the current analysis, we tried to identify the factors associated with brain metastases in stage III lung adenocarcinoma. The demographic and clinical characteristics, site and date of recurrence, and date of death were reviewed in patients with unresectable stage III lung adenocarcinoma who underwent concurrent platinum-based chemoradiotherapy. In total, 116 patients were identified with a median (range) age of 57 (35-74) years. Of these, 86 (74%) were men, all patients had platinum-based chemotherapy, and 100 (86%) received a total dose of 60 Gy in 30 fractions as definitive thoracic radiotherapy. Of the 95 patients with disease progression or recurrence, 19 (16%) developed brain metastases as the sole site of initial recurrence. A total of 43 (37%) patients developed brain metastases at some time during follow up. Time to brain metastases was significantly associated with the pretreatment carcinoembryonic antigen (CEA) value, with a hazard ratio (95% confidence interval) of 2.64 (1.39-5.02, P = 0.003). Patients who developed brain metastases as the first recurrent site had marginally better survival (log-rank test, P = 0.066) than those with metastases other than brain. In conclusion, stage III lung adenocarcinoma patients with an elevated CEA value before treatment had a higher risk of developing brain metastases after chemoradiotherapy. Further effort is mandatory to control brain metastases in this patient population by a therapeutic strategy based on the tumor histology and pretreatment CEA value. PMID- 22320684 TI - Enhanced photocatalytic reduction of aqueous Pb(II) over Ag loaded TiO2 with formic acid as hole scavenger. AB - In the present study, photocatalytic Pb(II) reduction over TiO(2) and Ag/TiO(2) catalysts in the presence of formic acid was explored to eliminate Pb(II) pollution in water. Ag/TiO(2) catalysts were prepared by the photo-deposition method and characterized using UV-Vis diffuse reflectance spectra, X-ray reflection diffraction, transmission electron microscopy and X-ray photoelectron spectroscopy. Ag deposition on TiO(2) led to enhanced photocatalytic Pb(II) reduction and the Ag/TiO(2) catalyst with a Ag loading amount of 0.99 wt.% exhibited the optimum photocatalytic activity. For Pb(II) reduction over Ag/TiO(2) with a Ag loading amount of 0.99 wt.%, initial Pb(II) reduction rate was found to be dependent on the initial concentrations of formic acid and Pb(II). Increasing initial Pb(II) concentration led to linearly increased initial Pb(II) reduction rate. At low formic acid concentration, in parallel, initial Pb(II) reduction rates increased with formic concentration, but remained nearly identical at high formic acid concentration. Solution pH impacted the photocatalytic Pb(II) reduction and after irradiation for 100 min Pb(II) was removed by 11.8%, 91.2% and 98.6% at pH of 0.8, 2.0 and 3.5, respectively, indicative of enhanced Pb(II) reduction with pH in the tested pH range. The results showed that Ag/TiO(2) displayed superior catalytic activity to TiO(2), highlighting the potential of using Ag/TiO(2) as a more effective catalyst for photocatalytic Pb(II) reduction. PMID- 22320685 TI - Optimization of hydrothermal synthesis of pure phase zeolite Na-P1 from South African coal fly ashes. AB - This study was aimed at optimizing the synthesis conditions for pure phase zeolite Na-P1 from three coal fly ashes obtained from power stations in the Mpumalanga province of South Africa. Synthesis variables evaluated were: hydrothermal treatment time (12-48 hours), temperature (100-160 degrees C) and varying molar quantities of water during the hydrothermal treatment step (H(2)O:SiO(2) molar ratio ranged between 0-0.49). The optimum synthesis conditions for preparing pure phase zeolite Na-P1 were achieved when the molar regime was 1 SiO(2): 0.36 Al(2)O(3): 0.59 NaOH: 0.49 H(2)O and ageing was done at 47 degrees C for 48 hours. The optimum hydrothermal treatment time and temperature was 48 hours and 140 degrees C, respectively. Fly ashes sourced from two coal-fired power plants (A, B) were found to produce nearly same high purity zeolite Na-P1 under identical conditions whereas the third fly ash (C) lead to a low quality zeolite Na-P1 under these conditions. The cation exchange capacity for the high pure phase was found to be 4.11 meq/g. These results highlight the fact that adjustment of reactant composition and presynthesis or synthesis parameters, improved quality of zeolite Na-P1 can be achieved and hence an improved potential for application of zeolites prepared from coal fly ash. PMID- 22320686 TI - Catalytic remediation of 2-propanol on Pt-Mn/gamma-Al2O3 bimetallic catalyst during catalytic combustion--experimental study and response surface methodology (RSM) modeling. AB - Process and composition variables of catalytic oxidation of 2-propanol on Pt Mn/gamma-Al(2)O(3) bimetallic catalysts were optimized and modeled by response surface methodology (RSM). 31 factorial experiments were designed by setting four factors at five levels: X (1) = amount of manganese loading (wt.% Mn = 1, 3, 5, 7, 9); X (2) = reaction temperature (25, 50, 75, 100, 125 degrees C); X (3) = calcination temperature (200, 300, 400, 500, 600 degrees C) and X (4) = calcination time (2, 3, 4, 5, 6 h). A second-order polynomial model and response surface were developed for 2-propanol conversion. The optimum conditions for 2 propanol complete conversion were 4.8wt.% manganese loading, 4h calcination time with 75 degrees C and 395 degrees C for reaction and calcination temperatures, respectively. A good correlation was found between experimental and predicted responses, confirming the reliability of the model. PMID- 22320687 TI - Bioaugmentation for polyacrylamide degradation in a sequencing batch reactor and contact oxidation reactor. AB - In the present study, one PAM degrading bacterial strain, originally named HWBI, was isolated from an activated sludge sample and used as an exogenous bacteria for bioaugmentation. The strain was primarily identified as Bacillus cereus. One contact oxidation reactor (COR) and one sequencing batch reactor (SBR) were bioaugmented with the HWBI, respectively, and the performance of the bioaugmented systems for PAM removal were investigated under long term operation. Results showed that for the COR augmented with HWBI, 70% of PAM was removed at the end of the 7th day after a single inoculation, and the removal efficiency remained at approximately 70% in the following 45 days after a single inoculation. For the SBR augmented with HWBI, 70% of PAM was removed at the end of the first operation cycle, and the removal remained at approximately 70% in the following eight cycles after a single inoculation. The results indicate that HWBI is an efficient exogenous bacteria for bioaugmentation for PAM removal. Although the COR and SBR were both appropriate reactors that may be used for treatment of PAM using bioaugmentation, the COR was found to be a more time-efficient method compared to the SBR. A molecular screening technique, terminal restriction fragment length polymorphism (T-RFLP), was applied to track the supplemented bacterial strain and to evaluate the effects of bioaugmentation on the microbial communities and to investigate the optimal bioaugmentation strategy. PMID- 22320688 TI - Assessment of the genotoxicity of heavy metals in Phaseolus vulgaris L. as a model plant system by Random Amplified Polymorphic DNA (RAPD) analysis. AB - Impact assessments of environmental pollutants are important in eco genotoxicology. A random amplified polymorphic DNA (RAPD) technique was used to detect genotoxicity-induced DNA damage in Phaseolus vulgaris L. from heavy metals at two different concentrations. The results from six 10-base pair (bp) random RAPD primers with 60-70% GC content used, showed a total of 295 RAPD fragments of 700-4000 bp in molecular size in the seedlings of untreated and treated samples, of which only 163 fragments were polymorphic. Polymorphisms became evident as the disappearance and/or appearance of DNA fragments in treated samples compared to the control. A dendrogram constructed using the Numerical Taxonomy and Multivariate Analysis System (NTSYSps), showed that the control group merged with groups treated with CuSO(4).5H(2)O (150 mg L(-1)) and MnSO(4).H(2)O (150 mg L( 1)) in a separate cluster. These groups were linked with all of the other samples treated with metals at concentrations of 150 mg L(-1) and CuSO(4).5H(2)O and Cd(NO(3))(2) at concentrations of 350 mg L(-1). Finally, the samples treated with metals at concentrations of 350 mg L(-1) together with NiSO(4) at the concentration of 150 mg L(-1), clustered separately. The DNA polymorphism detected by RAPD analysis offered a useful biomarker assay for the detection of toxic chemicals genotoxicity in plant model systems. PMID- 22320689 TI - Degradation of long-chain n-alkanes in soil microcosms by two actinobacteria. AB - The ability of two recently isolated actinobacteria, that degrade medium and long chain n-alkanes in laboratory water medium, was investigated in soil microcosms using different standard soils that were artificially contaminated with n-alkanes of different length (C(12)- C(20)- C(24)- C(30)). The two strains, identified as Nocardia sp. SoB and Gordonia sp. SoCp, revealed a similar high HC degradation efficiency with an average of 75% alkane degraded after 28 days incubation. A selectivity of bacteria towards n-alkanes of different length was detected as well as a consistent effect of soil texture and other soil physical chemical characteristics on degradation. It was demonstrated the specific aptitude of these selected strains towards specific environmental conditions. PMID- 22320690 TI - Computer controlled chamber measurements for clay adherence relevant for potential dioxin exposure through skin. AB - A computer-controlled mechanical chamber was used to control the contact between aluminum sheet samples laden with clay, and cotton sheet samples for the measurement of mass transfer. The contact parameters of pressure (20 to 60 kPa) and time (10 to 70 sec) were varied for 160 multiple experiments of mass soil transfer. Before log transformation the average transfer for 'First Transfer' of clay particles was 34.4 +/- 6.3 mg/8.97 cm(2) while that for 'Total Transfer' was 36.1 +/- 6.8 mg/8.97 cm(2). Second contact, therefore, resulted in an average transfer of 1.70 +/- 0.76 mg/8.97 cm(2). These values are well above adherence values measured for potting soil and sand as reported for previous experiments using the same methodologies. Based on the univariate analysis and the multiple regression analysis we were able to see some effect of parameters on the clay adherence values. The effect of pressure increases was significant for the higher levels of 50 and 60 kPa. In addition, we observed that increases in temperature were significant for 'First Transfer,' and less so for 'Total Transfer'. Past experiments using potting soil and play sand show high adherence values to human cadaver skin over cotton sample; the same scenario would be expected for clay. This data set can be used to improve estimates of dermal exposure to dioxins found in ball clays often used by artisans in the making of pottery. PMID- 22320691 TI - Levels and distribution of synthetic musks and polycyclic aromatic hydrocarbons in sludge collected from Guangdong Province. AB - The levels and distribution of six polycyclic musks, three nitromusks and 15 polycyclic aromatic hydrocarbons (PAHs) were investigated in sludge collected from 19 municipal wastewater treatment plants (WWTPs) in six cities in Guangdong Province, China. PAHs were detected in all of the sludge samples, and the levels of the total 15 PAHs ranged from 177.2-4421.8 MUg/kg dry weight (dw). Four polycyclic musks, 4-acetyl-1,1-dimethyl-6-tert-butylindan (ADBI), 6-acetyl 1,1,2,3,3,5-hexamethylindan (AHMI), 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8 hexamethylcyclopenta (g) -2-benzopyran (HHCB) and 7-acetyl -1,1,3,4,4,6 hexamethyl-1,2,3,4-tetrahydro naphthalene (AHTN), were found in these samples. The total concentrations of polycyclic musks varied from 794.4-12960.3 MUg/kg dw, with HHCB and AHTN being the main components. Of the three nitromusks, 2,6 dinitro-3-methoxy-4-tert- butyl - toluene (MA) was only found in one sludge sample at the limit of detection (LOD) level, while 1-tert-butyl-3,5-dimethyl 2,4,6-trinitrobenzene (Musk xylene, MX) and 4-acetyl-1-tert-butyl-3,5-dimethyl 2,6-dinitrobenzene (Musk ketone, MK) were found at levels ranging from the LOD to 65.8 MUg/kg dw and LOD to 172.7 MUg/kg dw, respectively, in most of the sludge samples. The PAHs, polycyclic musks and nitro musks were also shown to have various distribution patterns, possibly due to their different wastewater sources and wastewater treatment technology. PMID- 22320692 TI - The impact of bacteria of circulating water on apatite-nepheline ore flotation. AB - A new phenomenon has been identified and studied-the impact of bacteria on the benefication process of non-sulphide ores using circulating water supply-a case study of apatite-nepheline ore. It is shown that bacteria deteriorate the floatability of apatite due to their interaction with active centres of calcium containing minerals and intense flocculation, resulting in a decrease of the flotation process selectivity thus deteriorating the quality of concentrate. Based on the comparative analysis of primary sequences of 16S rRNA genes, there have been identified dominating bacteria species, recovered from the circulating water used at apatite-nepheline concentrating mills, and their phylogenetic position has been determined. All the bacteria were related to gamma Proteobacteria, including the Acinetobacter species, Pseudomonas alcaliphila, Ps. plecoglossicida, Stenotrophomonas rhizophila. A method of non-sulphide ores flotation has been developed with consideration of the bacterial factor. It consists in use of small concentrations of sodium hypochlorite, which inhibits the development of bacteria in the flotation of apatite-nepheline ores. PMID- 22320693 TI - Fractionation and availability of heavy metals in tannery sludge-amended soil and toxicity assessment on the fully-grown Phaseolus vulgaris cultivars. AB - This study was conducted to assess the effect of tannery sludge on the bush bean (Phaseolus vulgaris) cultivars fully-grown on a culture sandy soil, as tannery sludge is valuable to improve soil fertility but long term studies evaluating the effect on fully grown plants are scarce. Tannery sludge amendments (0, 0.77, 1.54, 3.08 and 6.16 g tannery sludge kg(-1) soil) were characterized and the main heavy metals identified (Cr, Mn, Fe, K, and Zn) later on sequentially and singly extracted, for soil fractionation and availability determination, respectively. Metals showed different fractionation and availability patterns, being the most toxic metal (Cr) found to primarily bind to the carbonate fraction in soil, while almost 10% of the total Cr was available for plant uptake. In the green house experiments, bush bean cultivars exposed to increasing tannery sludge amendments were evaluated at different plant stages. Metal accumulation and physiological parameters (chlorophyll, carotenoids, nitrate reductase activity and dry weight) were determined. Toxicity was primarily due to Cr, stimulating or affecting the response of physiological parameters and suppressing seed formation at the highest tannery sludge ratio. Metals were mainly accumulated in the roots of bush beans, diminishing in the upper part of the plants with minimal translocation to seeds, supposing little risk for human consumption. Additionally, important correlations, antagonistic and synergistic relationships were observed between the extracted metals and metal accumulation in plant tissues. PMID- 22320694 TI - Evaluation of natural zeolite as microorganism support medium in nitrifying batch reactors: influence of zeolite particle size. AB - An evaluation of natural zeolite as a microorganism carrier in nitrifying reactors operated in batch mode was carried out. Specifically, the influence of zeolite particle sizes of 0.5, 1.0 and 2.0 mm in diameter on microorganism adherence to zeolite, ammonium adsorption capacity and the identification of microbial populations were assessed. The greatest amount of total biomass adhered was observed for a zeolite particle size of 1 mm (0.289 g) which was achieved on the 12th day of operation. The highest ammonium adsorption capacity was observed for a zeolite particle size of 0.5 mm, which was 64% and 31% higher than that observed for particle sizes of 1.0 and 2.0 mm, respectively. The maximum de sorption values were also found for a zeolite particle size of 0.5 mm, although when equilibrium was reached the ammonium concentrations were similar to those observed for a zeolite particle size of 1.0 mm. It was also found that the experimental data on ammonium adsorption fitted very well to the Freundlich isotherm for the three particle sizes studied. Finally, the nitrifying reactors showed similar microbial populations independently of the particle size used as microorganism carrier. The dominant bacterial community was Gammaproteobacteria making up 80% of the total population found. Betaproteobacteria were also identified and made up 12% approx. of the total population. Ammonium Oxidant Betaproteobacteria and Nitrobacter were also detected. PMID- 22320695 TI - Determination of perfluorinated alkylated substances in sediments and sediment core from the Gulf of Gdansk, Baltic Sea. AB - Perfluorinated alkylated substances (PFAS) have been determined in surface sediments and sediment core from Gulf of Gdansk, Baltic Sea. Perfluorooctanesulphonate (PFOS), perfluorohexanesulphonate (PFHxS), perfluorodecanoate (PFDA), perfluoronanoate (PFNA), perfluorooctanoate (PFOA), perfluoroheptanoate (PFHpA), perfluoroundecanote (PFUnDA), perfluorododecanoate (PFDoDA) and perfluorohexanoate (PFHxA) were quantified after isotopic dilution ((13)C(4) PFOS and (13)C(4) PFOA), liquid-liquid extractions by methanol and acetonitrile, cleanup by Envi-Carb, OasisWAX and Envi-Carb and final measurement by HPLC-MS/MS. PFOS, PFHxS, PFUnDA, PFDA, PFNA and PFOA were found in Baltic Sea sediments in concentrations exceeding the method limit of quantification (LOQ) of 2 pg/g. PFOS was detected in concentration up to 0.896 ng/g dry weight and PFHxS up to 0.326 ng/g dw, which shows on a weak pollution. PFOS (48-74%) or PFHxS (45 56%) dominated in PFAS composition of sediments surveyed. Supplemental materials are available for this article. Go to the publisher's online edition of the Journal of Environmental Science and Health, Part A to view the free supplemental file. PMID- 22320696 TI - Oil refinery wastewater treatment using physicochemical, Fenton and Photo-Fenton oxidation processes. AB - The objective of this study was to investigate the application of advanced oxidation processes (AOPs) to the treatment of wastewaters contaminated with hydrocarbon oil. Three different oil-contaminated wastewaters were examined and compared: (i) a 'real' hydrocarbon wastewater collected from an oil refinery (Conoco-Phillips Whitegate refinery, County Cork, Ireland); (ii) a 'real' hydrocarbon wastewater collected from a car-wash facility located at a petroleum filling station; and (iii) a 'synthetic' hydrocarbon wastewater generated by emulsifying diesel oil and water. The AOPs investigated were Fe(2+)/H(2)O(2) (Fenton's reagent), Fe(2+)/H(2)O(2)/UV (Photo-Fenton's reagent) which may be used as an alternative to, or in conjunction with, conventional treatment techniques. Laboratory-scale batch and continuous-flow experiments were undertaken. The photo Fenton parametric concentrations to maximize COD removal were optimized: pH = 3, H(2)O(2) = 400 mg/L, and Fe(2+) = 40 mg/L. In the case of the oil-refinery wastewater, photo-Fenton treatment achieved approximately 50% COD removal and, when preceded by physicochemical treatment, the percentage removal increased to approximately 75%. PMID- 22320697 TI - QSPR models for prediction of the soil sorption coefficient (log KOC) values of 209 polychlorinated trans-azobenzenes (PCt-ABs). AB - The values of the soil sorption coefficient (K(OC)) have been computed for 209 environmentally relevant trans polychlorinated azobenzenes (PCABs) lacking experimental partitioning data. The quantitative structure-property relationship (QSPR) approach and artificial neural networks (ANN) predictive ability used in models based on geometry optimalization and quantum-chemical structural descriptors, which were computed on the level of density functional theory (DFT) using B3LYP functional and 6-311++G** basis set and of the semi-empirical quantum chemistry method for property parameterization (PM6) of the molecular orbital package (MOPAC). An experimentally available data on physical and chemical properties of PCDD/Fs and PCBs were used as reference data for the QSPR models and ANNs predictions in this study. Both calculation methods gave similar results in term of absolute log K(OC) values, while the PM6 model generated in the MOPAC was a much more efficient compared to the DFT model in GAUSSIAN. The estimated values of log K(OC) varied between 4.93 and 5.62 for mono-, 5.27 and 7.46 for di , 6.46 and 8.09 for tri-, 6.65 and 9.11 for tetra-, 6.75 and 9.68 for penta-, 6.44 and 10.24 for hexa-, 7.00 and 10.36 for hepta-, 7.09 and 9.82 octa-, 8.94 and 9.71 for nona-Ct-ABs, and 9.26 and 9.34 for deca-Ct-AB. Because of high log K(OC) values PCt-ABs could be classified as compounds with high affinity to the particles of soil, sediments and organic matter. PMID- 22320698 TI - Prediction of subcooled vapor pressures (log PL) of 399 polychlorinated trans azoxybenzenes by using the QSPR and ANN approach. AB - Environmentally relevant partitioning properties such as the sub-cooled vapor pressures (log PL) have been predicted for 399 congeners of chloro-trans azoxybenzene (C-t-AOBs) by two computational methods. The quantitative structure property relationship (QSPR), an approach which is based on geometry optimalization and quantum-chemical structural descriptors in RM1 and DFT methods and artificial neural networks (ANNs), an approach that predicts abilities that give similar results of estimated log P(L) and the accuracy of the methods was also similar. The RM1 method was less time consuming and less costly compared to calculations by the DFT method. Estimated from the RM1 and DFT methods of log P(L) values of 399 Ct-AOBs varied between -1.98 to -0.93 and -1.83 to -0.79 for Mono-, 3.12 to -1.46 and -3.00 to -1.46 for Di-, -4.03 to -1.39 and -3.53 to 1.67 for Tri-, -4.75 to -2.33 and -4.59 to -1.91 for Tetra-, -5.37 to -2.59 and 5.42 to -2.09 for Penta-, -5.82 to -2.88 and -5.66 to -2.58 for Hexa-, -5.88 to 3.24 and -5.60 to -2.93 for Hepta-, -6.28 to -4.33 and -5.60 to -4.29 for Octa-, 6.54 to -5.28 and -5.66 to -4.93 for NonaCt-AOBs, and -6.59 and -5.61 for DecaCt AOB. According to a common classification of environmental contaminants and by sub-cooled vapor pressure values, MonoCt-AOBs and a few of the Di- and TriCt-AOBs (log P(L)from -2 to 0) fall into the group of compounds that are relatively well mobile in the ambient environment, while most of the Di- to HeptaCt-AOBs (log P(L) < -4 to -2) mobility is relatively weak. Octa- and NonaCt-AOBs and DecaCt AOB (log P(L) < -4) are also weak mobile contaminants. PMID- 22320699 TI - Characterization and electrochemical treatment of landfill leachate. AB - A combined treatment approach using advanced oxidation, electrochemical methods and microwaves was developed and applied for the treatment of landfill leachate taken from Piskornica (Koprivnica, Croatia) sanitary landfill. Due to the complex nature of the effluent and extremely low bio-degradability (BOD(5)/COD ratio = 0.01) the purification of the leachate started with pre-treatment with ozone followed by simultaneous ozonation and electrocoagulation/electrooxidation using the set of iron and aluminum electrodes, and finally, the degradation of organic residue and ammonia with microwaves. Applied treatment approach resulted in clear, colorless and odorless effluent with the values of all measured parameters significantly lower compared to the upper permissible limit for discharge into the environment. The removal percentages of the parameters: color, turbidity, suspended solids, ammonia, COD and iron following the combined treatment were 98.43%, 99.48%, 98.96%, 98.80%, 94.17% and 98.56%, respectively. PMID- 22320700 TI - Biogas production from switchgrass under experimental conditions simulating U.S. digester operations. AB - Lignocellulosic feedstocks have high energy content and have been co-digested with sewage or manure biosolids in Europe for many years. However, it is unclear whether the current U.S. anaerobic digesters are capable of co-digesting lignocellulosic feedstocks without experiencing operational problems. We evaluated co-digestion of switchgrass with sewage biosolids under laboratory conditions similar to common U.S. digesters. Results indicated that finely-ground or ensiled switchgrass could be readily co-digested with sewage biosolids under typical U.S. digester conditions. Concentration up to 4% solids (representing up to 47% of VS added) achieved good specific methane yields and up to 74% energy conversion efficiency while maintaining acceptable VS removal. No evidence of solids accumulation, mixing problems, or floating debris was noted. However, fine grinding switchgrass is energy intensive and likely to be cost-prohibitive. Moreover, ensiling produced a wide array of particle sizes and the effects of ensiling could not be fully separated from effects due to smaller particle size. Coarsely ground switchgrass, however, did not digest well. It had a low specific methane yield and quickly led to digester operational problems, even at the 2% solids level. Further research is needed to identify pretreatment methods that are more practical than fine-grinding. Ensiling appears promising, and should be studied under full-scale ensiling and digestion conditions to assure that observed effects were not due to smaller particle sizes achieved under laboratory conditions. Other, low-cost pretreatment methods also deserve study as a means of allowing lignocellulosic feedstocks to be co-digested in current U.S. anaerobic digesters. PMID- 22320701 TI - Polonium, uranium and plutonium radionuclides in aquatic and land ecosystem of Poland. AB - This article presents the results of study about distribution, inflow and accumulation of polonium, uranium and plutonium in aquatic and land environment of Poland and the southern Baltic Sea. Radionuclides of (210)Po, (234)U and (238)U as well as (239+240)Pu and (241)Pu are strongly accumulated in Baltic organisms and plants and transferred through the trophic chain. The values of bioconcentration factor (BCF) in Baltic plants and animals are higher for polonium and plutonium in comparison with uranium. The principal source of radionuclides in the southern Baltic Sea is their inflow with rivers. Total annual runoff of polonium, uranium and plutonium from the Vistula and the Odra as well as the Pomeranian rivers were calculated at 95 GBq of (210)Po, 750 GBq of (234+238)U and 160 MBq of (238+239+240)Pu. Seasonal and spatial variability of (210)Po, (238)U and (239+240)Pu levels in the Vistula and the Odra drainage basins were assessed by application of neural-network based classification, especially cluster analysis (CA), principal component analysis (PCA) and self organizing maps (SOM). The result for the Vistula river indicated correlation between polonium and plutonium as well as polonium and uranium. In the Odra drainage basin, the biggest differences were observed in the case of (238)U. To assess if there are statistically significant differences in mean concentration values of (210)Po, (238)U and (239+240)Pu for the Vistula and the Odra rivers drainage basins were obtained by used of the non-parametric tests. Comparing to the Vistula catchment area, statistically differences concentration of (210)Po and (239+240)Pu in all year was observed for river samples collected on the Odra drainage basin. PMID- 22320702 TI - Nonylphenol polyethoxylate in hospital wastewater: a study of the subproducts of electrocoagulation. AB - Chromatographic procedures such as solid phase extraction and high performance liquid chromatography coupled with a fluorescence detector (SPE-HPLC-FLD), were carried out to determine the concentrations of the surfactant nonylphenol ethoxylate (9 ethylene oxide units, NP9EO) and its biodegradation product, 4 nonylphenol (NP), in samples collected from the wastewater treatment system at the University Hospital (HUSM) of the Federal University of Santa Maria. The results showed a high concentration of NP9EO in all the collected samples (0.075 4.12 mg L(-1)) and an almost complete absence of NP. In addition, electrocoagulation (EC) of NP9EO was carried out in aqueous solution and in the HUSM effluent. A NP9EO removal rate of 95 % was achieved from the aqueous solution, following a pseudo-first-order kinetics. Through LC-MS measurements in aqueous solutions, it was possible to determine the formation of short-chain nonylphenol ethoxylate (NPEO), such as nonyl-phenoxy acetic acid (NP1EC), after 30 min of EC. In the case of the HUSM wastewater, the NP9EO removal was 89 %, and the chemical oxygen demand (COD) abatement was 26 %. A respirometric test was conducted to measure the increase of biodegradability during the EC and the aqueous samples were found to be less readily biodegradable before the 30-min period of electrocoagulation than after it had been completed. PMID- 22320703 TI - Beneficial effects of beta-blockers on left ventricular function and cellular energy reserve in patients with heart failure. AB - Beta-blockers have been shown to improve left ventricular (LV) function in patients with heart failure. The aim of this study is to non-invasively assess, by means of in vivo 31P-magnetic resonance spectroscopy (31P-MRS), the effects of beta-blockers on LV cardiac phosphocreatine and adenosine triphosphate (PCr/ATP) ratio in patients with heart failure. Ten heart failure patients on full medical therapy were beta-blocked by either carvedilol or bisoprolol. Before and after 3 months of treatment, exercise testing, 2D echocardiography, MRS, New York Heart Association (NYHA) class, ejection fraction (EF), maximal rate-pressure product and exercise metabolic equivalent system (METS) were evaluated. Relative concentrations of PCr and ATP were determined by cardiac 31P-MRS. After beta blockade, NYHA class decreased (from 2.2 +/- 0.54 to 1.9 +/- 0.52, P = 0.05), whereas EF (from 33 +/- 7 to 44 +/- 6%, P = 0.0009) and METS (from 6.74 +/- 2.12 to 8.03 +/- 2.39, P = 0.01) increased. Accordingly, the mean cardiac PCr/ATP ratio increased by 33% (from 1.48 +/- 0.22 to 1.81 +/- 0.48, P = 0.03). Beta blockade-induced symptomatic and functional improvement in patients with heart failure is associated to increased PCr/ATP ratio, indicating preservation of myocardial high-energy phosphate levels. PMID- 22320704 TI - Spin-polarized Rb2 interacting with bosonic He atoms: potential energy surface and quantum structures of small clusters. AB - A new full-dimension potential energy surface of the three-body He Rb2(3Sigma(u)(+)) complex and a quantum study of small (4He)(N)-Rb2(3Sigma(u)(+)) clusters, 1 <= N <= 4, are presented. We have accurately fitted the ab initio points of the interaction to an analytical form and addressed the dopant's vibration, which is found to be negligible. A Variational approach and a Diffusion Monte Carlo technique have been applied to yield energy and geometric properties of the selected species. Our quantum structure calculations show a transition in the arrangements of the helium atoms from N = 2, where they tend to be separated across the diatomic bond, to N = 4, in which a closer packing of the rare gas particles is reached, guided by the dominance of the He-He potential over the weaker interaction of the latter adatoms with the doping dimer. The deepest well of the He-Rb2 interaction is placed at the T-shape configuration, a feature which causes the dopant to be located as parallel to the helium "minidroplet". Our results are shown to agree with previous findings on this and on similar systems. PMID- 22320705 TI - Development of an accelerated solvent extraction, ultrasonic derivatisation LC MS/MS method for the determination of the marker residues of nitrofurans in freshwater fish. AB - A rapid method using accelerated solvent extraction (ASE) and ultrasound enhanced derivatisation has been developed for the quantitative determination of metabolites of nitrofurans, namely 3-amino-2-oxalidinone (AOZ), 5 morpholinomethyl-3-amino-2-oxalidinone (AMOZ), 1-amino-hydantoin (AHD) and semicarbazide (SEM), in muscle and skin of carp and finless eel. The target analytes were extracted using ASE, ultrasonic derivatisation for 1 h and then purified by solid phase extraction. Averaged decision limits (CCalpha) and detection capability (CCbeta) of the method were in the range of 0.07-0.13 and 0.31-0.49 ug kg-1 in carp and finless eel, respectively. The accuracy in terms of recovery was in the range 77.2-97.4%. The simplified and traditional methods were compared with incurred residue samples. The simplified method reduced the derivatisation time and has been applied to the determination of nitrofurans residues in fish. PMID- 22320706 TI - Weight, body mass index and behaviour change in a commercially run lifestyle programme for young people. AB - BACKGROUND: There are few practical, scalable, community-based solutions that provide ongoing support to combat the recent rapid rise in obesity in young people. A commercial weight management organisation (CWMO) has developed a tailored version of its programme for young people. The present study assessed the programme's impact on self-reported body weight, body mass index (BMI; kg m( 2) ) and health-related behaviour changes in participating young people. METHODS: Seventy-nine current young members completed a web-based questionnaire on age, height, weight and self-reported eating and activity behaviours for when they joined the programme and at the time of survey. Inclusion criteria were age 11-15 years old and membership for at least 1 month. Subjects completed the questionnaire online via the CWMO website. This was a retrospective observational study without a control group. All data were self-reported. RESULTS: Mean (SD) age was 13.4 (1.4) years and start weight was 78.5 (16.7) kg; 67% were >99th centile for BMI. Mean (SD) attendance was 23 (19) weeks; weight change was -5.0 (4.5) kg; BMI change was -2.5 (2.0) kg m(-2) ; and BMI Z-score change was -0.5 (0.4) (all P < 0.001). Height increased by 0.01 (0.03) m (P < 0.01); however, height Z-score remained unchanged. Regression analysis showed that BMI Z-score change was related to increased fruit and vegetable intake (P = 0.012), as well as a decrease in avoidance of moderate and intense activity (both P < 0.003). CONCLUSIONS: This programme for overweight and obese young people helped implement behaviour and lifestyle changes that were associated with significant reductions in self-reported weight and BMI Z-score, without compromising growth in height. PMID- 22320707 TI - Neonatal candidiasis: results of an 8 year study. AB - BACKGROUND: The aim of the present study was to evaluate the risk factors, demographic features, treatment and clinical outcome associated with candidemia in a neonatal intensive care unit (NICU) within an 8 year period. METHODS: The data of infants who were diagnosed as having candidemia, were evaluated. RESULTS: Between January 2000 and December 2007, a total of 28 candidemia episodes were identified in 28 infants. A 1.1% candidemia incidence was documented in the neonatal intensive care unit (NICU). The species most frequently causing candidemia were Candida parapsilosis (57.1%), followed by C. albicans (42.9%). The main predisposing factors for candidemia with C. parapsilosis included presence of maternal pre-eclampsia, prematurity, prolonged mechanical ventilation, prolonged total parenteral nutrition and presence of jaundice. Retinopathy of prematurity and bronchopulmonary dysplasia were the most frequently seen underlying illnesses in infants with C. parapsilosis. In the present study, 13 infants (46.4%) had evidence of organ dissemination. The mortality rate was 42.8% in infants with candidemia. Mean leukocyte counts and mean C-reactive protein were significantly higher in neonates who died compared with those who survived. CONCLUSION: Candida parapsilosis (57.1%) was the leading causative organism, followed by C. albicans (42.9%) in infants. The rate of organ dissemination in the present cases was high. The mortality rate was 42.8% in infants with candidemia. PMID- 22320708 TI - Magnetic tuning of all-organic binary alloys between two stable radicals. AB - Mixtures of 2-(4,5,6,7-tetrafluorobenzimidazol-2-yl)-4,4,5,5-tetramethyl-4,5 dihydro-1H-imidazole-3-oxide-1-oxyl (F4BImNN) and 2-(benzimidazol-2-yl)-4,4,5,5 tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (BImNN) crystallize as solid solutions (alloys) across a wide range of binary compositions. (F4BImNN)(x)(BImNN)((1-x)) with x < 0.8 gives orthorhombic unit cells, while x >= 0.9 gives monoclinic unit cells. In all crystalline samples, the dominant intermolecular packing is controlled by one-dimensional (1D) hydrogen-bonded chains that lead to quasi-1D ferromagnetic behavior. Magnetic analysis over 0.4 300 K indicates ordering with strong 1D ferromagnetic exchange along the chains (J/k = 12-22 K). Interchain exchange is estimated to be 33- to 150-fold weaker, based on antiferromagnetic ordered phase formation below Neel temperatures in the 0.4-1.2 K range for the various compositions. The ordering temperatures of the orthorhombic samples increase linearly as (1 - x) increases from 0.25 to 1.00. The variation is attributed to increased interchain distance corresponding to decreased interchain exchange, when more F4BImNN is added into the orthorhombic lattice. The monoclinic samples are not part of the same trend, due to the different interchain arrangement associated with the phase change. PMID- 22320709 TI - Kin selection may contribute to lek evolution and trait introgression across an avian hybrid zone. AB - Understanding the mechanism(s) that favour cooperation among individuals competing for the same resources provides direct insights into the evolution of grouping behaviour. In a hybrid zone between golden-/yellow-collared (Manacus vitellinus) and white-collared (Manacus candei) manakins, males form aggregations composed of white and yellow males solely to attract females ('mixed leks'). Previous work shows that yellow males in these mixed leks experience a clear mating advantage over white males, resulting in the preferential introgression of yellow plumage allele(s) into the white species. However, the yellow male mating advantage only occurs in mixed leks with high frequencies of yellow males, and only a few of these males probably mate. Hence, it remains unclear why unsuccessful males join leks. Here, we used microsatellite markers to estimate pairwise relatedness among males within and between leks to test whether indirect genetic benefits of helping kin ('kin selection') can promote grouping. We found that yellow males are significantly more related to each other within than between leks, while relatedness among white males did not differ within and between leks. This suggests that yellow males may indirectly enhance their own reproductive success by preferentially lekking with relatives because yellow plumage is under positive frequency-dependent selection (positive FDS). Our results are consistent with the hypothesis that kin selection may promote grouping and facilitate positive FDS for yellow males, mediating the movement of yellow plumage across this hybrid zone. PMID- 22320710 TI - Polymeric optodes based on upconverting nanorods for fluorescent measurements of pH and metal ions in blood samples. AB - Optical thin films incorporating NaYF(4):Er,Yb upconverting nanorods and chromoionophore ETH 5418 in hydrophobic polymer matrixes have been developed for the first time to measure pH and metal ions based on the ion-exchange mechanism. The absorption spectra of protonated and unprotonated ETH 5418 overlap the two emission peaks of upconverting material, respectively, which makes the inert nanorods ion-sensitive. Optodes for pH and metal ions (Na(+), K(+), Ca(2+), and Cu(2+)) were investigated and exhibited excellent sensitivity, selectivity, and reproducibility. Because of excitation by the 980 nm laser source, detection in the near-infrared region at 656 nm, and high quantum yield of the nanorods in hydrophobic membrane, the proposed sensors have been successfully used in whole blood measurements with minimized background absorption and sample autofluorescence. PMID- 22320711 TI - Low glucose suspend: ready for prime time? PMID- 22320712 TI - Endothelin-1 induces neutrophil recruitment in adaptive inflammation via TNFalpha and CXCL1/CXCR2 in mice. AB - Endothelin mediates neutrophil recruitment during innate inflammation. Herein we address whether endothelin-1 (ET-1) is involved in neutrophil recruitment in adaptive inflammation in mice, and its mechanisms. Pharmacological treatments were used to determine the role of endothelin in neutrophil recruitment to the peritoneal cavity of mice challenged with antigen (ovalbumin) or ET-1. Levels of ET-1, tumour necrosis factor alpha (TNFalpha), and CXC chemokine ligand 1 (CXCL1) were determined by enzyme-linked immunosorbent assay. Neutrophil migration and flow cytometry analyses were performed 4 h after the intraperitoneal stimulus. ET 1 induced dose-dependent neutrophil recruitment to the peritoneal cavity. Treatment with the non-selective ET(A)/ET(B) receptor antagonist bosentan, and selective ET(A) or ET(B) receptor antagonists BQ-123 or BQ-788, respectively, inhibited ET-1- and ovalbumin-induced neutrophil migration to the peritoneal cavity. In agreement with the above, the antigen challenge significantly increased levels of ET-1 in peritoneal exudates. The ET-1- and ovalbumin-induced neutrophil recruitment were reduced in TNFR1 deficient mice, and by treatments targeting CXCL1 or CXC chemokine receptor 2 (CXCR2); further, treatment with bosentan, BQ-123, or BQ-788 inhibited ET-1- and antigen-induced production of TNFalpha and CXCL1. Furthermore, ET-1 and ovalbumin challenge induced an increase in the number of cells expressing the Gr1(+) markers in the granulocyte gate, CD11c(+) markers in the monocyte gate, and CD4(+) and CD45(+) (B220) markers in the lymphocyte gate in an ET(A)- and ET(B)-dependent manner, as determined by flow cytometry analysis, suggesting that ET-1 might be involved in the recruitment of neutrophils and other cells in adaptive inflammation. Therefore, the present study demonstrates that ET-1 is an important mediator for neutrophil recruitment in adaptive inflammation via TNFalpha and CXCL1/CXCR2-dependent mechanism. PMID- 22320713 TI - Porphyrin biodistribution in UV-exposed murine skin after methyl- and hexyl aminolevulinate incubation. AB - Topical photodynamic therapy (PDT) with methyl-aminolevulinate (MAL) is a well established treatment for precancerous skin lesions and non-melanoma skin cancer. Treatment outcomes are less effective for thick than for superficial lesions, which are presumed to be due to insufficient PpIX biodistribution in tumour tissue. Hexyl-aminolevulinate (HAL) is a more lipophilic photosensitizer precursor than MAL and may penetrate the skin to a greater depth and more homogeneously. We compared HAL- and MAL-induced PpIX accumulation in specific skin compartments using concentrations of 2%, 6% and 20% HAL and MAL on long-term UV-irradiated mouse skin. Furthermore, 20% HAL and 20% MAL were applied to non irradiated skin. Porphyrin fluorescence was measured by fluorescence microscopy in selected skin regions: the epidermis, superficial dermis, deep dermis and sebaceous gland epithelium down to a depth of 1 mm. We found higher PpIX fluorescence intensities in epidermis and sebaceous gland epithelium from 2%, 6% and 20% HAL (median 72-104 au) than in corresponding concentrations of MAL (median 35-69 au) (P < 0.01). Fluorescence intensities in the superficial (35 au) and deep dermis (32 au) were similar for HAL and MAL (P = 0.51) and lower than epidermal fluorescence intensities (P < 0.001). Significantly, higher median PpIX fluorescence intensities (64 au) were found in 20% MAL-incubated skin irradiated with UV than in non-irradiated skin (48 au) (P < 0.001). HAL-induced fluorescence intensities did not depend on UV exposure (HAL 20%, UV: 72 au, non-UV: 70 au) (P = 0.87). In conclusion, HAL express high affinity for epidermis and sebaceous gland epithelium, and MAL for actinically damaged skin, which raises future perspectives for improved selectivity in PDT. PMID- 22320714 TI - Effect of a third application of toothpastes (1450 and 5000 ppm F), including a 'massage' method on fluoride retention and pH drop in plaque. AB - OBJECTIVE: The aim was to investigate fluoride (F) retention in plaque, saliva and pH drop in plaque using high-F toothpaste (5000 ppm F) or standard toothpaste (1450 ppm F) twice a day or 3-times a day. A method using the toothpaste as a 'lotion' and massaging the buccal surfaces with the fingertip was also evaluated. MATERIALS AND METHODS: The investigation had a randomized, single-blinded, cross over design and 16 subjects participated in six brushing regimes: (1) 5000 ppm F; twice a day, (2) 5000 ppm; 3-times/day, (3) 5000 ppm; twice a day, plus the 'massage' method once a day, (4) 1450 ppm F; twice a day, (5) 1450 ppm; 3 times/day and (6) 1450 ppm; twice a day, plus the 'massage' method once a day. The outcome measure was F retention in plaque, saliva and the plaque-pH change after a sucrose rinse. RESULTS: The highest F concentration was found using high F toothpaste (No 1-3) and differed significantly from those with 1450 ppm (No 4 6). Brushing with high-F toothpaste 3-times a day (No 2) resulted in a 3.6-times higher F saliva value compared with standard toothpaste twice a day (No 4) (p < 0.001). Increasing the frequency of application, from twice to 3-times a day, increased the F retention in plaque significantly when the two methods for application 3-times a day were pooled (p < 0.05). Brushing with 5000 and 1450 ppm toothpastes twice a day plus the 'massage' once a day resulted in the same F concentration in saliva and plaque as brushing 3-times a day with the same paste. CONCLUSION: A third application of toothpaste is increasing the F retention and toothpaste as a 'lotion' and massaging the buccal surfaces with the fingertip may be a simple and inexpensive way of delivering F a third time during the day. PMID- 22320715 TI - Association of increased ligand cyclophilin A and receptor CD147 with hypoxia, angiogenesis, metastasis and prognosis of tongue squamous cell carcinoma. AB - AIMS: We evaluated the association of ligand cyclophilin A (CypA) and receptor CD147 with hypoxia, angiogenesis, lymph node metastasis and prognosis of patients with tongue squamous cell carcinoma (TSCC). METHODS AND RESULTS: We studied the expression of CypA, CD147, hypoxia-inducible factor 1alpha (HIF-1alpha), vascular endothelial growth factor A and C (VEGF-A and VEGF-C) protein by immunohistochemistry in 80 specimens of TSCC. CypA, CD147, HIF-1alpha, VEGF-A and VEGF-C were overexpressed in TSCCs, and were significantly higher than those in normal oral mucosa tissues (P<0.01). Increased ligand CypA and receptor CD147 correlated significantly with expression of HIF-1alpha, VEGF-A and VEGF-C. A significant relationship between VEGF-A and VEGF-C was also detected (P<0.01). Patients with overexpression of CypA, CD147, HIF-1alpha and VEGF-C had significantly worse overall survival (P<0.05) using Kaplan-Meier analysis. Multivariate Cox regression analysis showed that HIF-1alpha, recurrence and distant metastasis were independent prognostic factors on overall survival in TSCC patients. CONCLUSIONS: The association of expression of ligand CypA and receptor CD147 with carcinogenesis, hypoxia, angiogenesis, metastasis and prognosis of TSCC suggests that ligand CypA and receptor CD147 may have prognostic value and could be regarded as potential therapeutic targets in TSCC. PMID- 22320716 TI - Cumulative risk assessment of phthalate exposure of Danish children and adolescents using the hazard index approach. AB - Human risk assessment of chemicals is traditionally presented as the ratio between the actual level of exposure and an acceptable level of exposure, with the acceptable level of exposure most often being estimated by appropriate authorities. This approach is generally sound when assessing the risk of individual chemicals. However, several chemicals may concurrently target the same receptor, work through the same mechanism or in other ways induce the same effect(s) in the body. In these cases, cumulative risk assessment should be applied. The present study uses biomonitoring data from 129 Danish children and adolescents and resulting estimated daily intakes of four different phthalates. These daily intake estimates are used for a cumulative risk assessment with anti androgenic effects as the endpoint using Tolerable Daily Intake (TDI) values determined by the European Food Safety Authorities (EFSA) or Reference Doses for Anti-Androgenicity (RfD AA) determined by Kortenkamp and Faust [Int J Androl 33 (2010) 463] as acceptable levels of exposure. United States Environmental Protection Agency Reference Doses (US EPA RfD) could not be used as none of them identifies anti-androgenic effects as the most sensitive endpoint for the phthalates included in this article. Using the EFSA TDI values, 12 children exceeded the hazard quotient for the sum of di-n-butyl phthalate and di-iso-butyl phthalate (?DBP((i+n))) and one child exceeded the hazard quotient for di-(2 ethylhexyl)phthalate (DEHP). Nineteen children exceeded the cumulated hazard index for three phthalates. Using the RfD AA values, one child exceeded the hazard quotient for DEHP and the same child exceeded the cumulated hazard index for four phthalates. The EFSA TDI approach thus is more restrictive and identifies ?DBP((i+n)) as the compound(s) associated with the greatest risk, while DEHP is the compound associated with the greatest risk when using the RfD AA approach. PMID- 22320718 TI - Reviews, perspectives, features: what's the difference? PMID- 22320717 TI - Suppression of azoxymethane-induced colonic preneoplastic lesions in rats by 1 methyltryptophan, an inhibitor of indoleamine 2,3-dioxygenase. AB - The escape of preneoplastic cells from the immune system, which is caused by immune tolerance, occurs during the development of several types of tumors. Indoleamine 2,3-dioxygenase (IDO) plays a critical role in the induction of immune tolerance. In the present study we investigated the effects of 1 methyltryptophan (1-MT), an IDO inhibitor, and (-)-epigallocatechin gallate (EGCG), the major catechin in green tea, on the development of azoxymethane (AOM) induced colonic preneoplastic lesions by focusing on the inhibition of IDO. To induce colonic premalignant lesions, male F344 rats were injected with AOM (20 mg/kg body weight, s.c.) once a week for 2 weeks. They also received 0.2% 1-MT or 0.1% EGCG in their drinking water for 4 weeks, starting 1 week before the first dose of AOM. Both 1-MT and EGCG significantly decreased the total number of aberrant crypt foci and beta-catenin-accumulated crypts, which overexpressed IDO protein. Treatment with EGCG decreased IDO mRNA expression in both the colonic epithelium and stroma of rats induced by AOM. The AOM-induced increase in cyclooxygenase-2 mRNA expression in the colonic stroma was significantly decreased by EGCG. Furthermore, AOM-induced increases in IDO activity in the serum and stroma were significantly inhibited by 1-MT and EGCG. Inhibition of IDO activity by 1-MT and EGCG was also observed in cell-free assays. These findings suggest that upregulation of IDO activity is observed in the early stages of colon carcinogenesis and that the use of IDO inhibitors, such as 1-MT and EGCG, which suppress the occurrence of colonic preneoplastic lesions, could be a novel strategy for the chemoprevention of colon cancer. PMID- 22320719 TI - Quantum locality and equilibrium properties in low-temperature parahydrogen: a multiscale simulation study. AB - Parahydrogen is the spin-zero singlet state of molecular hydrogen, which at low temperature (between 14 and 25 K) is in a fluid state. A classical treatment of the system leads to unphysical freezing, and the inclusion of quantum delocalization of the molecule is then required to obtain a realistic description of its equilibrium properties. In the present work, we employ the classical quantum adaptive resolution method AdResS to investigate the spatial extension of quantum delocalization effects in the bulk fluid at low temperature. Specifically, we simulate a small, spherical region of the system in full quantum detail: this region is coupled to a bulk of coarse-grained particles with classical, quantum-derived effective interactions obtained from quantum simulations. The two regions are interfaced through open boundaries and in conditions of thermodynamic equilibrium. Structural properties of the fluid, namely, pair distribution functions, are measured for different sizes of the quantum region. The results of this work show that, for the thermodynamic conditions corresponding to the range of temperature between 14 and 25 K, the bead-based, quantum structural properties of low-temperature parahydrogen are deemed local and do not require the support of an explicit quantum bulk. PMID- 22320720 TI - Nuclear signatures on the molecular harmonic emission and the attosecond pulse generation. AB - In this paper, we theoretically investigate the nuclear signatures effects, i.e., the initial vibrational state and the isotopic effects on the generations of the molecular high-order harmonics and the attosecond pulses when the model H(2)(+)/D(2)(+) ions are exposed to a 5 fs/800 nm chirp pulse. The numerical solution of the time-dependent Schrodinger equation for these vibrating molecule ions shows that the intensities of the harmonic spectra are reinforced with the enhancement of the initial vibrational state. Moreover, through the investigation of the isotopic effect, we find that more intense harmonics are generated in the lighter nucleus. Furthermore, by optimizing the chirp pulse under the optimal initial vibrational state, an intense ultrabroad supercontinuum with a 325 eV bandwidth can be obtained. By properly superposing the harmonic spectrum, an attosecond pulse as short as 57 as (16 as) is generated without (with) phase compensation. PMID- 22320721 TI - Fitting properties from density functional theory based molecular dynamics simulations to parameterize a rigid water force field. AB - In the quest towards coarse-grained potentials and new water models, we present an extension of the force matching technique to parameterize an all-atom force field for rigid water. The methodology presented here allows to improve the matching procedure by first optimizing the weighting exponents present in the objective function. A new gauge for unambiguously evaluating the quality of the fit has been introduced; it is based on the root mean square difference of the distributions of target properties between reference data and fitted potentials. Four rigid water models have been parameterized; the matching procedure has been used to assess the role of the ghost atom in TIP4P-like models and of electrostatic damping. In the former case, burying the negative charge inside the molecule allows to fit better the torques. In the latter, since short-range interactions are damped, a better fit of the forces is obtained. Overall, the best performing model is the one with a ghost atom and with electrostatic damping. The approach shown in this paper is of general validity and could be applied to any matching algorithm and to any level of coarse graining, also for non-rigid molecules. PMID- 22320722 TI - Dressed adiabatic and diabatic potentials to study conical intersections for F + H2. AB - We follow a suggestion by Lipoff and Herschbach [Mol. Phys. 108, 1133 (2010)] and compare dressed and bare adiabatic potentials to get insight regarding the low energy dynamics (e.g., cold reaction) taking place in molecular systems. In this particular case, we are interested to study the effect of conical intersections (ci) on the interacting atoms. For this purpose, we consider vibrational dressed adiabatic and vibrational dressed diabatic potentials in the entrance channel of reactive systems. According to our study, the most one should expect, in case of F + H(2), is a mild effect of the (1, 2) ci on its reactive/exchange process--an outcome also supported by experiment. This happens although the corresponding dressed and bare potential barriers (and the corresponding van der Waals potential wells) differ significantly from each other. PMID- 22320723 TI - Iterative diagonalization in the state-averaged multi-configurational time dependent Hartree approach: excited state tunneling splittings in malonaldehyde. AB - An iterative block Lanczos-type diagonalization scheme utilizing the state averaged multi-configurational time-dependent Hartree (MCTDH) approach is introduced. Combining propagation in real and imaginary time and using a set of initial seed wavefunctions corresponding to excitations via the different components of the dipole moment vector, the scheme can favorably be used to selectively compute vibrational states which show high intensities in vibrational absorption spectra. Tunneling splitted vibrational states in double well systems can be described particularly efficient employing an increased set of seed wavefunctions which includes symmetric and anti-symmetric wavefunctions simultaneously. The new approach is used to study the tunneling splittings of the vibrationally excited states of malonaldehyde. Full-dimensional multi-layer MCTDH calculations are performed and results for the tunneling splittings of several excited vibrational states can be obtained. The calculated tunneling splittings agree reasonably well with available experimental data. Order of magnitude differences between tunneling splittings of different vibrationally excited states are found and interpreted. PMID- 22320724 TI - Effect of dimensionality on the continuum percolation of overlapping hyperspheres and hypercubes. AB - We show analytically that the [0, 1], [1, 1], and [2, 1] Pade approximants of the mean cluster number S for both overlapping hyperspheres and overlapping oriented hypercubes are upper bounds on this quantity in any Euclidean dimension d. These results lead to lower bounds on the percolation threshold density eta(c), which become progressively tighter as d increases and exact asymptotically as d -> infinity, i.e., eta(c) -> 2(-d). Our analysis is aided by a certain remarkable duality between the equilibrium hard-hypersphere (hypercube) fluid system and the continuum percolation model of overlapping hyperspheres (hypercubes). Analogies between these two seemingly different problems are described. We also obtain Percus-Yevick-like approximations for the mean cluster number S in any dimension d that also become asymptotically exact as d -> infinity. We infer that as the space dimension increases, finite-sized clusters become more ramified or "branch like." These analytical estimates are used to assess simulation results for eta(c) up to 20 dimensions in the case of hyperspheres and up to 15 dimensions in the case of hypercubes. Our analysis sheds light on the radius of convergence of the density expansion for S and naturally leads to an analytical approximation for eta(c) that applies across all dimensions for both hyperspheres and oriented hypercubes. Finally, we describe the extension of our results to the case of overlapping particles of general anisotropic shape in d dimensions with a specified orientational probability distribution. PMID- 22320725 TI - When does the non-variational nature of second-order Moller-Plesset energies manifest itself? All-electron correlation energies for open-shell atoms from K to Br. AB - All-electron correlation energies E(c) are not very well known for open-shell atoms with more than 18 electrons. The complete basis-set (CBS) limits of second order Moller-Plesset (MP2) perturbation theory energies are obtained for open shell atoms by computations in large basis sets combined with a knowledge of the MP2/CBS limit for the next larger closed-shell atom with the same valence shell structure. Then higher-order correlation corrections are found by coupled-cluster calculations using basis sets that are not quite as large. The method is validated for the open-shell atoms from Al to Cl for which E(c) is reasonably well established. Then, the method is used to obtain non-relativistic E(c) values, probably accurate to 3%, for the open-shell atoms of the fourth period: K, Sc-Cu, and Ga-Br. These energies are compared with the predictions of 19 density functionals and may be useful for the parameterization of new ones. The results show that MP2 overestimates |E(c)| for atoms heavier than Fe. PMID- 22320726 TI - Nonadiabatic excited-state molecular dynamics: numerical tests of convergence and parameters. AB - Nonadiabatic molecular dynamics simulations, involving multiple Born-Oppenheimer potential energy surfaces, often require a large number of independent trajectories in order to achieve the desired convergence of the results, and simulation relies on different parameters that should be tested and compared. In addition to influencing the speed of the simulation, the chosen parameters combined with the frequently reduced number of trajectories can sometimes lead to unanticipated changes in the accuracy of the simulated dynamics. We have previously developed a nonadiabatic excited state molecular dynamics methodology employing Tully's fewest switches surface hopping algorithm. In this study, we seek to investigate the impact of the number of trajectories and the various parameters on the simulation of the photoinduced dynamics of distyrylbenzene (a small oligomer of polyphenylene vinylene) within our developed framework. Various user-defined parameters are analyzed: classical and quantum integration time steps, the value of the friction coefficient for Langevin dynamics, and the initial seed used for stochastic thermostat and hopping algorithms. Common approximations such as reduced number of nonadiabatic coupling terms and the classical path approximation are also investigated. Our analysis shows that, at least for the considered molecular system, a minimum of ~400 independent trajectories should be calculated in order to achieve statistical averaging necessary for convergence of the calculated relaxation timescales. PMID- 22320727 TI - Trajectory-guided configuration interaction simulations of multidimensional quantum dynamics. AB - We propose an approach to modelling multidimensional quantum systems which uses direct-dynamics trajectories to guide wavefunction propagation. First, trajectory simulations are used to generate a sample of dynamically relevant configurations on the potential energy surface (PES). Second, the sampled configurations are used to construct an n-mode representation of the PES using a greedy algorithm. Finally, the time-dependent Schrodinger equation is solved using a configuration interaction expansion of the wavefunction, with individual basis functions derived directly from the 1-mode contributions to the n-mode PES. This approach is successfully demonstrated by application to a 20-dimensional benchmark problem describing tunnelling in the presence of coupled degrees of freedom. PMID- 22320728 TI - The sign problem and population dynamics in the full configuration interaction quantum Monte Carlo method. AB - The recently proposed full configuration interaction quantum Monte Carlo method allows access to essentially exact ground-state energies of systems of interacting fermions substantially larger than previously tractable without knowledge of the nodal structure of the ground-state wave function. We investigate the nature of the sign problem in this method and how its severity depends on the system studied. We explain how cancellation of the positive and negative particles sampling the wave function ensures convergence to a stochastic representation of the many-fermion ground state and accounts for the characteristic population dynamics observed in simulations. PMID- 22320729 TI - Stochastic mapping of the Michaelis-Menten mechanism. AB - The Michaelis-Menten mechanism is an extremely important tool for understanding enzyme-catalyzed transformation of substrates into final products. In this work, a computationally viable, full stochastic description of the Michaelis-Menten kinetic scheme is introduced based on a stochastic equivalent of the steady-state assumption. The full solution derived is free of restrictions on amounts of substance or parameter values and is used to create stochastic maps of the Michaelis-Menten mechanism, which show the regions in the parameter space of the scheme where the use of the stochastic kinetic approach is inevitable. The stochastic aspects of recently published examples of single-enzyme kinetic studies are analyzed using these maps. PMID- 22320730 TI - The multi-configuration electron-nuclear dynamics method applied to LiH. AB - The multi-configuration electron-nuclear dynamics (MCEND) method is a nonadiabatic quantum dynamics approach to the description of molecular processes. MCEND is a combination of the multi-configuration time-dependent Hartree (MCTDH) method for atoms and its antisymmetrized equivalent MCTDHF for electrons. The purpose of this method is to simultaneously describe nuclear and electronic wave packets in a quantum dynamical way, without the need to calculate potential energy surfaces and diabatic coupling functions. In this paper we present first exemplary calculations of MCEND applied to the LiH molecule, and discuss computational and numerical details of our implementation. PMID- 22320731 TI - Exploring the competition between localization and delocalization of the neutral soliton defect in polyenyl chains with the orbital optimized second order opposite spin method. AB - Theory and implementation of the analytical nuclear gradient is presented for orbital optimized scaled opposite-spin perturbation theory (O2). Evaluation of the O2 analytical gradient scales with the 4th power of molecular size, like the O2 energy. Since the O2 method permits optimization of the orbitals in the presence of wavefunction-based electron correlation, it is suitable for problems where correlation effects determine the competition between localization and delocalization of an odd electron, or hole. One such problem is the description of a neutral soliton defect on an all-trans polyacetylene chain with an odd number of carbon atoms. We show that the results of the O2 method compare well to benchmark values for small polyenyl radicals. O2 is also efficient enough to be applied to longer chains where benchmark coupled cluster methods are unfeasible. For C(41)H(43), unrestricted orbital O2 calculations yield a soliton length of about 9 carbon atoms, while other unrestricted orbital methods such as Hartree Fock, and the B3LYP and omegaB97X-D density functionals, delocalize the soliton defect over the entire chain. The O2 result is about half the width inferred experimentally. PMID- 22320732 TI - Quasi-variational coupled cluster theory. AB - We extend our previous work on the construction of new approximations of the variational coupled cluster method. By combining several linked pair functional transformations in such a way as to give appropriately balanced infinite-order contributions, in order to approximate (L) well at all orders, we formulate a new quantum chemical method, which we name quasi-variational coupled cluster. We demonstrate this method to be particularly robust in the regime of strong static electron correlation, improving significantly on our earlier approximate variational coupled cluster approach. PMID- 22320733 TI - Search for a small hole in a cavity wall by intermittent bulk and surface diffusion. AB - We study the search of a small round hole in the wall of a spherical cavity by a diffusing particle, which can reversibly bind to the cavity wall and diffuse on the surface being in the bound state. There are two channels for the particle first passage to the hole, through the bulk, and through the surface. We propose a coarse-grained model of the search process and use it to derive simple approximate formulas for the mean time required for the particle to reach the hole for the first time and for the probability of the first passage to the hole through the bulk channel. This is done for two distributions of the particle starting point: (1) Uniform distribution over the cavity volume and (2) uniform distribution over the cavity wall. We check the accuracy of the approximate formulas by comparing their predictions with the corresponding quantities found by solving the mixed bulk-surface diffusion problem numerically by the finite difference method. The comparison shows excellent agreement between the analytical and numerical results. PMID- 22320734 TI - Quadrupole-bound anions: efficacy of positive versus negative quadrupole moments. AB - A pseudopotential method is utilized to study the critical stability of model anions formed by long-range quadrupolar molecular potentials. Results indicate that critical quadrupole moments of simple point-charge triads do not serve well as predictors of real quadrupole-bound anions of systems with negative moments. PMID- 22320735 TI - Angle-resolved metastable fragment yields spectra of N2 and CO in K-edge excitation energy region. AB - Angle-resolved metastable fragments yields spectra have been measured in the N 1s ionization region of the N(2) and C 1s ionization region of CO. These spectra are compared with zero kinetic energy electron and photoelectron spectra. It has been shown that an isotropic metastable fragments yields spectra are almost identical with the ZEKE spectrum, whereas metastable fragments yields spectra with the Sigma-Sigma transition show similarity with photoelectron spectra. This means that these spectra clearly contain information about two shake-up mechanisms: conjugate and direct shake-up processes. All the peaks in the metastable photofragment spectra can be assigned as either satellite states or double/triple excitation states. Thus, it was shown that angle-resolved metastable photofragment spectroscopy could be used to help characterize multi-electron excitation states in general. PMID- 22320736 TI - Mg impurity in helium droplets. AB - Within the diffusion Monte Carlo approach, we have determined the structure of isotopically pure and mixed helium droplets doped with one magnesium atom. For pure (4)He clusters, our results confirm those of Mella et al. [J. Chem. Phys. 123, 054328 (2005)] that the impurity experiences a transition from a surface to a bulk location as the number of helium atoms in the droplet increases. Contrarily, for pure (3)He clusters Mg resides in the bulk of the droplet due to the smaller surface tension of this isotope. Results for mixed droplets are presented. We have also obtained the absorption spectrum of Mg around the 3s3p (1)P(1) <- 3s(2) (1)S(0) transition. PMID- 22320737 TI - Low energy collisions of CN(X2Sigma+) with He in magnetic fields. AB - A theoretical investigation of the He-CN((2)Sigma(+)) complex is presented. We perform ab initio calculations of the interaction potential energy surface and carry out accurate calculations of bound energy levels of the complex including the molecular fine structure. We find the potential has a shallow minimum and supports seven and nine bound levels in complex with (3)He and (4)He, respectively. Based on the potential the quantum scattering calculation is then implemented for elastic and inelastic cross sections of the magnetically trappable low-field-seeking state of CN((2)Sigma(+)) in collision with (3)He atom. The cold collision properties and the influence of the external magnetic field as well as the effect of the uncertainty of interaction potential on the collisionally induced Zeeman relaxation are explored and discussed in detail. The ratios of elastic to inelastic cross sections are large over a wide range of collision energy, magnetic field, and scaling factor of the potential, suggesting helium buffer gas loading and cooling of CN in a magnetic trap is a good prospect. PMID- 22320738 TI - Ultrafast ring opening in 1,3-cyclohexadiene investigated by simplex-based spectral unmixing. AB - We use spectral unmixing to determine the number of transient photoproducts and to track their evolution following the photo-excitation of 1,3-cyclohexadiene (CHD) to form 1,3,5-hexatriene (HT) in the gas phase. The ring opening is initiated with a 266 nm ultraviolet laser pulse and probed via fragmentation with a delayed intense infrared 800 nm laser pulse. The ion time-of-flight (TOF) spectra are analyzed with a simplex-based spectral unmixing technique. We find that at least three independent spectra are needed to model the transient TOF spectra. Guided by mathematical and physical constraints, we decompose the transient TOF spectra into three spectra associated with the presence of CHD, CHD(+), and HT, and show how these three species appear at different times during the ring opening. PMID- 22320739 TI - Dynamics of H+ + CO at E(Lab) = 30 eV. AB - The astrophysically relevant system H(+) + CO (v(i) = 0) -> H(+) + CO (v(f)) at E(Lab) = 30 eV is studied with the simplest-level electron nuclear dynamics (SLEND) method. This investigation follows previous successful SLEND studies of H(+) + H(2) and H(+) + N(2) at E(Lab) = 30 eV [J. Morales, A. Diz, E. Deumens, and Y. Ohrn, J. Chem. Phys. 103(23), 9968 (1995); C. Stopera, B. Maiti, T. V. Grimes, P. M. McLaurin, and J. A. Morales, J. Chem. Phys. 134(22), 224308 (2011)]. SLEND is a direct, time-dependent, variational, and non-adiabatic method that adopts a classical-mechanics description for the nuclei and a single determinantal wavefunction for the electrons. A canonical coherent-states (CS) procedure associated with SLEND reconstructs quantum vibrational properties from the SLEND classical dynamics. Present SLEND results include reactivity predictions, snapshots of the electron density evolution, average vibrational energy transfers, rainbow angle predictions, total and vibrationally resolved differential cross sections (DCS), and average vibrational excitation probabilities. SLEND results are compared with available data from experiments and vibrational close-coupling rotational infinite-order sudden (VCC-RIOS) approximation calculations. Present simulations employ four basis sets: STO-3G, 6 31G, 6-31G**, and cc-pVDZ to determine their effect on the results. SLEND simulations predict non-charge-transfer scattering and CO collision-induced dissociation as the main reactions. SLEND/6-31G, /6-31G**, and /cc-pVDZ predict rainbow angles and total DCS in excellent agreement with experiments and more accurate than their VCC-RIOS counterparts. SLEND/6-31G** and /cc-pVDZ predict vibrationally resolved DCS for v(f) = 0-2 in satisfactory experimental agreement, but less accurate than their comparable H(+) + CO VCC-RIOS and H(+) + H(2) and H(+) + N(2) SLEND results. SLEND/6-31G** and /cc-pVDZ predict qualitatively correct average vibrational excitation probabilities, which are quantitatively correct for v(f) = 2, but under(over)estimated for v(f) = 0(1). Discrepancies in some H(+) + CO SLEND vibrational properties, not observed in H(+) + H(2) and H(+) + N(2) SLEND results, are attributed to the moderately overestimated SLEND vibrational energy through its effect upon the canonical CS probabilities. Correction of that energy to its experimental values produces a remarkable improvement in the average vibrational excitation probabilities. Ways to obtain more accurate vibrational properties with higher-level versions of electron nuclear dynamics are discussed. PMID- 22320740 TI - Coupled-cluster, Moller Plesset (MP2), density fitted local MP2, and density functional theory examination of the energetic and structural features of hydrophobic solvation: water and pentane. AB - The interaction potentials between immiscible polar and non-polar solvents are a major driving force behind the formation of liquid:liquid interfaces. In this work, the interaction energy of water-pentane dimer has been determined using coupled-cluster theory with single double (triple) excitations [CCSD(T)], 2nd order Moller Plesset perturbation theory (MP2), density fitted local MP2 (DF LMP2), as well as density functional theory using a wide variety of density functionals and several different basis sets. The M05-2X exchange correlation functionals exhibit excellent agreement with CCSD(T) and DF-LMP2 after taking into account basis set superposition error. The gas phase water-pentane interaction energy is found to be quite sensitive to the specific pentane isomer (2,2-dimethylpropane vs. n-pentane) and relative orientation of the monomeric constituents. Subsequent solution phase cluster calculations of 2,2 dimethylpropane and n-pentane solvated by water indicate a positive free energy of solvation that is in good agreement with available experimental data. Structural parameters are quite sensitive to the density functional employed and reflect differences in the two-body interaction energy calculated by each method. In contrast, cluster calculations of pentane solvation of H(2)O solute are found to be inadequate for describing the organic solvent, likely due to limitations associated with the functionals employed (B3LYP, BHandH, and M05-2X). PMID- 22320741 TI - Cold collisions of complex polyatomic molecules. AB - We introduce a method for classical trajectory calculations to simulate collisions between atoms and large rigid asymmetric-top molecules. We investigate the formation of molecule-helium complexes in buffer-gas cooling experiments at a temperature of 6.5 K for molecules as large as naphthalene. Our calculations show that the mean lifetime of the naphthalene-helium quasi-bound collision complex is not long enough for the formation of stable clusters under the experimental conditions. Our results suggest that it may be possible to improve the efficiency of the production of cold molecules in buffer-gas cooling experiments by increasing the density of helium. In addition, we find that the shape of molecules is important for the collision dynamics when the vibrational motion of molecules is frozen. For some molecules, it is even more crucial than the number of accessible degrees of freedom. This indicates that by selecting molecules with suitable shape for buffer-gas cooling, it may be possible to cool molecules with a very large number of degrees of freedom. PMID- 22320742 TI - The electronic spectrum of the C(s)-C11H3 radical. AB - The electronic gas-phase absorption spectrum of the bent carbon-chain radical, HC(4)CHC(6)H with C(s) symmetry, is recorded in the 595 nm region by cavity ring down spectroscopy through an expanding hydrogen plasma. An unambiguous spectroscopic identification becomes possible from a systematic deuterium labeling experiment. A comparison of the results with recently reported spectra of the nonlinear HC(4)CHC(4)H and HC(4)C(C(2)H)C(4)H radicals with C(2v) symmetry provides a more comprehensive understanding of the molecular behavior of pi conjugated bent carbon-chain systems upon electronic excitation. We find that the electronic excitation in the bent carbon-chain HC(4)CHC(2n)H (n = 1-4) series exhibits a similar trend as in the linear HC(2n+1)H (n = 3-6) series, shifting optical absorptions towards longer wavelengths for increasing overall bent chain lengths. The pi-conjugation in bent HC(4)CHC(2n)H (n = 1-4) chains is found to be generally smaller than in the linear HC(2n+1)H (n = 3-6) case for equivalent numbers of C-atoms. The addition of an electron-donating group to the bent chain causes a slight decrease of the effective conjugation. PMID- 22320743 TI - Nonadiabatic dynamics of O(1D) + N2(X1Sigmag+) -> O(3P) + N2(X1Sigmag+) on three coupled potential surfaces: symmetry, Coriolis, spin-orbit, and Renner-Teller effects. AB - We present the spin-orbit (SO) and Renner-Teller (RT) quantum dynamics of the spin-forbidden quenching O((1)D) + N(2)(X(1)Sigma(g)(+)) -> O((3)P) + N(2)(X(1)Sigma(g)(+)) on the N(2)O X(1)A', a(3)A", and b(3)A' coupled PESs. We use the permutation-inversion symmetry, propagate coupled-channel (CC) real wavepackets, and compute initial-state-resolved probabilities and cross sections sigma(j(0)) for the ground vibrational and the first two rotational states of N(2), j(0) = 0 and 1. Labeling symmetry angular states by j and K, we report selection rules for j and for the minimum K value associated with any electronic state, showing that a(3)A" is uncoupled in the centrifugal-sudden (CS) approximation at j(0) = 0. The dynamics is resonance-dominated, the probabilities are larger at low K, sigma(j(0)) decrease with the collision energy and increase with j(0), and the CS sigma(0) is lower than the CC one. The nonadiabatic interactions play different roles on the quenching dynamics, because the X(1)A' b(3)A' SO effects are those most important while the a(3)A"-b(3)A' RT ones are negligible. PMID- 22320744 TI - Ultrafast resonance-enhanced multiphoton ionization in the azabenzenes: pyridine, pyridazine, pyrimidine, and pyrazine. AB - We report on the ultrafast photoionization of pyridine, pyridazine, pyrimidine, and pyrazine. These four molecules represent a systematic series of perturbations into the structure of a benzene ring which explores the substitution of a C-H entity with a nitrogen atom, creating a heterocyclic structure. Data are recorded under intense-field, single-molecule conditions. The pulses (50 fs, 800 nm) are focused into the molecular vapor, and ion mass spectra are recorded for intensities of ~10(13) W/cm(2) to ~10(15) W/cm(2). We measure ion yields in the absence of the focal volume effect without the need for deconvolution of the data. For all targets, stable singly- and doubly-charged parent ions (C(6-n)H(6 n)N(n)(+(+))) are observed with features suggesting resonance-enhanced ionization. From the intensity dependence of the ion yield, we infer that excitation occurs both through (1)pipi* transitions (remnants of the benzene structure) and through (1)npi* transitions, the latter being a result of Rydberg like excitations of the lone pair electrons of the nitrogen atoms. Stability against intense-field fragmentation is also discussed. PMID- 22320745 TI - Free energy landscapes for homogeneous nucleation of ice for a monatomic water model. AB - We simulate the homogeneous nucleation of ice from supercooled liquid water at 220 K in the isobaric-isothermal ensemble using the MW monatomic water potential. Monte Carlo simulations using umbrella sampling are performed in order to determine the nucleation free energy barrier. We find the Gibbs energy profile to be relatively consistent with that predicted by classical nucleation theory; the free energy barrier to nucleation was determined to be ~18 k(B)T and the critical nucleus comprised ~85 ice particles. Growth from the supercooled liquid gives clusters that are predominantly cubic, whilst starting with a pre-formed subcritical nucleus of cubic or hexagonal ice results in the growth of predominantly that phase of ice only. PMID- 22320746 TI - Cage occupancies in the high pressure structure H methane hydrate: a neutron diffraction study. AB - A neutron diffraction study was performed on the CD(4) : D(2)O structure H clathrate hydrate to refine its CD(4) fractional cage occupancies. Samples of ice VII and hexagonal (sH) methane hydrate were produced in a Paris-Edinburgh press and in situ neutron diffraction data collected. The data were analyzed with the Rietveld method and yielded average cage occupancies of 3.1 CD(4) molecules in the large 20-hedron (5(12)6(8)) cages of the hydrate unit cell. Each of the pentagonal dodecahedron (5(12)) and 12-hedron (4(3)5(6)6(3)) cages in the sH unit cell are occupied with on average 0.89 and 0.90 CD(4) molecules, respectively. This experiment avoided the co-formation of Ice VI and sH hydrate, this mixture is more difficult to analyze due to the proclivity of ice VI to form highly textured crystals, and overlapping Bragg peaks of the two phases. These results provide essential information for the refinement of intermolecular potential parameters for the water-methane hydrophobic interaction in clathrate hydrates and related dense structures. PMID- 22320747 TI - Investigation of intermolecular interactions in perylene films on Au(111) by infrared spectroscopy. AB - Intermolecular interactions in crystalline perylene films on Au(111) have been investigated by Fourier transform infrared spectroscopy. Dimer modes of vibrations are observed in the crystalline film, in contrast to the monomer modes found for isolated perylene molecules. These dimers are formed via hydrogen bonding in the sandwich herringbone structure of the crystalline alpha-phase. Davydov splitting of both the monomer and the dimer modes is observed due to resonance dynamic intermolecular interaction. The splitting of monomer modes into three distinct vibrations and the occurrence of the dimer modes confirm that the film crystallizes in the alpha phase, which is in line with the x-ray diffraction results. The frequency shift and band broadening at elevated temperature have been attributed to the cubic and quartic anharmonic interactions. PMID- 22320748 TI - Finite-difference time-domain simulation of light induced charge dynamics in silver nanoparticles. AB - We use a finite-difference time-domain (FDTD) approach to describe and control light-induced charge dynamics via two constructs consisting of nanoscale silver cylinders. The charge dynamics is found to be significantly different from the energy dynamics intensively studied in the past in similar systems. It is shown that two-color sources with a tunable relative phase introduce the opportunity to control the charge dynamics via a simple and interesting control mechanism, namely, the time evolution of the charge is directly tied to the instantaneous value of the source fields. Hence, our ability to shape laser pulses and tailor their relative phases and amplitudes translates directly into the possibility of manipulating charge oscillations within metal nanoparticle arrays. PMID- 22320749 TI - Coarse-grained models for the solvents dimethyl sulfoxide, chloroform, and methanol. AB - The time- and length-scale accessible to molecular dynamics simulations of biomolecular systems using atomic-level (AL) models is most limited by the calculation of the solvent-solvent interactions, which comprise the majority of the interactions and yet are seldom of specific interest. Coarse-graining (CG), in which multiple solvent molecules are subsumed into a single bead, provides a means of overcoming this limitation without resorting to implicit solvation models, which basically misrepresent the hydrophobic effect. Most existing CG models, however, do not explicitly include electrostatic interactions, and thus fail to reproduce important properties of the solvent such as dielectric screening. Moreover, CG models for one type of solvent molecule are seldom compatible with those for other solvents. Here, we develop polarizable CG models for the solvents dimethyl sulfoxide, chloroform, and methanol that are compatible with an existing CG model for water. The inclusion of polarizability greatly improves the reproduction of thermodynamic data measured experimentally and calculated from AL simulations for both the pure liquids and binary mixtures. PMID- 22320750 TI - Competing effects of rare gas atoms in matrix isolation spectroscopy: a case study of vibrational shift of BeO in Xe and Ar matrices. AB - We investigate the vibrational shift of beryllium oxide (BeO) in Xe matrix as well as in Ar matrix environments by mixed quantum-classical simulation and examine the origin of spectral shift in details. BeO is known to form strong chemical complex with single rare gas atom, and it is predicted from the gas phase calculations that vibrational frequencies are blueshifted by 78 cm(-1) and 80 cm(-1) upon formation of XeBeO and ArBeO, respectively. When the effects of other surrounding rare gas atoms are included by Monte Carlo simulations, it is found that the vibrational frequencies are redshifted by 21 cm(-1) and 8 cm(-1) from the isolated XeBeO and ArBeO complexes, respectively. The vibrational shift of XeBeO in Ar matrix is also calculated and compared with experimental data. In all simulations examined in this paper, the calculated vibrational frequency shifts from the isolated BeO molecule are in reasonable agreement with experimental values. The spectral shift due to the rare-gas-complex formation of RgBeO (Rg = Xe or Ar) is not negligible as seen in the previous studies, but it is shown in this paper that the effects of other surrounding rare gas atoms should be carefully taken into account for quantitative description of the spectral shifts and that these two effects are competing in vibrational spectroscopy of BeO in matrix environments. PMID- 22320751 TI - Structurally determined directionality identifies the boundary between mobile and immobile domains in a disordered material. AB - The structure and available degrees of freedom of an amorphous configuration can determine the location of dynamic heterogeneities. In the same way, these features can also determine the directionality of the particle motion. In this paper we propose that directionality can be attributed to those particles that only participate in a single unconstrained motion. The consequences of this suggestion in terms of the spatial distribution of particles with high directionality are explored using a random bond model. PMID- 22320752 TI - Methyl group rotation, 1H spin-lattice relaxation in an organic solid, and the analysis of nonexponential relaxation. AB - We report (1)H spin-lattice relaxation measurements in polycrystalline 4,4' dimethoxybiphenyl at temperatures between 80 and 300 K at NMR frequencies of omega(0)/2pi = 8.50, 22.5, and 53.0 MHz. The data are interpreted in terms of the simplest possible Bloch-Wangsness-Redfield methyl group hopping model. Different solid states are observed at low temperatures. The (1)H spin-lattice relaxation is nonexponential at higher temperatures where a stretched-exponential function fits the data very well, but this approach is phenomenological and not amenable to theoretical interpretation. (We provide a brief literature review of the stretched-exponential function.) The Bloch-Wangsness-Redfield model applies only to the relaxation rate that characterizes the initial (1)H magnetization decay in a high-temperature nonexponential (1)H spin-lattice relaxation measurement. A detailed procedure for determining this initial relaxation rate is described since large systematic errors can result if this is not done carefully. PMID- 22320753 TI - Photoluminescence spectroscopy of pure pentacene, perfluoropentacene, and mixed thin films. AB - We report detailed temperature dependent photoluminescence (PL) spectra of pentacene (PEN), perfluoropentacene (PFP), and PEN:PFP mixed thin films grown on SiO(2). PEN and PFP are particularly suitable for this study, since they are structurally compatible for good intermixing and form a model donor/acceptor system. The PL spectra of PEN are discussed in the context of existing literature and compared to the new findings for PFP. We analyze the optical transitions observed in the spectra of PEN and PFP using time-dependent density functional theory calculations. Importantly, for the mixed PEN:PFP film we observe an optical transition in PL at 1.4 eV providing evidence for coupling effects in the blend. We discuss a possible charge-transfer (CT) and provide a tentative scheme of the optical transitions in the blended films. PMID- 22320754 TI - Dispersion-corrected density functional theory calculations of the molecular binding of n-alkanes on Pd(111) and PdO(101). AB - We investigated the molecular binding of n-alkanes on Pd(111) and PdO(101) using conventional density functional theory (DFT) and the dispersion-corrected DFT-D3 method. In agreement with experimental findings, DFT-D3 predicts that the n alkane desorption energies scale linearly with the molecule chain length on both surfaces, and that n-alkanes bind more strongly on PdO(101) than on Pd(111). The desorption energies computed using DFT-D3 are slightly higher than the measured values for n-alkanes on Pd(111), though the agreement between computation and experiment is a significant improvement over conventional DFT. The measured desorption energies of n-alkanes on PdO(101) and the energies computed using DFT D3 agree to within better than 2.5 kJ/mol (< 5%) for chain lengths up to n butane. The DFT-D3 calculations predict that the molecule-surface dispersion energy for a given n-alkane is similar in magnitude on Pd(111) and PdO(101), and that dative bonding between the alkanes and coordinatively unsaturated Pd atoms is primarily responsible for the enhanced binding of n-alkanes on PdO(101). From analysis of the DFT-D3 results, we estimate that the strength of an alkane eta(2)(H, H) interaction on PdO(101) is ~16 kJ/mol, while a single eta(1) H-Pd dative bond is worth about 10 kJ/mol. PMID- 22320755 TI - Mobility matrix of a spherical particle translating and rotating in a viscous fluid confined in a spherical cell, and the rate of escape from the cell. AB - The mobility matrix of a spherical particle moving in a spherical cavity, filled with a viscous incompressible fluid, and with no-slip boundary condition at the wall of the cavity, is evaluated from the Oseen tensor for the cavity by the method used by Lorentz for a particle near a planar wall. For the case that the particle is a rigid sphere with no-slip boundary condition the comparison with exact calculations shows that the approximation is quite accurate, provided the radius of the particle is small relative to that of the cavity, and provided the particle is not too close to the wall. The translational mobility is used to derive the diffusion tensor of a Brownian particle via an Einstein relation. The approximate result for the diffusion tensor is employed to estimate the rate of escape of a Brownian particle from a cavity with semipermeable wall. PMID- 22320756 TI - Surface area controlled heterogeneous nucleation. AB - Heterogeneous nucleation of liquid from a gas phase on nanoparticles has been studied under various saturation ratios and nuclei size. The probability of liquid droplet nucleation, especially at a low degree of deviation from equilibrium, was measured for both atmospheric aerosol particles and engineered nanoparticles Cr(2)O(3). The concept of a critical saturation ratio and the validity of the one-to-one relationship between the nuclei number and the number of droplets were examined. A transient zone between no nucleation and established nucleation termed the surface area controlled nucleation was observed. In this zone, the probability of stable phase formation is determined by the surface area of nuclei. There are two distinctive features of the surface area controlled nucleation: the nucleation probability is much less than 1 and is proportional to the surface area of nuclei. For condensation particle counters (CPCs) counting nanoparticles, these features mean that counts measured are proportional to the surface area of nanoparticles and, therefore, the CPCs counts can be calibrated to measure the surface area. PMID- 22320757 TI - A model for codependent reversible/irreversible growth processes. AB - A model for codependent growth that combines reversible and irreversible bond formation is developed. The system is composed of two processes: A reversible process which is fast but does not lead to a stable growth by itself, while the irreversible process is stable but is too slow to occur by itself. Therefore, neither the reversible nor the irreversible growth processes will occur separately, but their combination is shown to yield a new type of stable, codependent growth. Using kinetic Monte Carlo techniques we simulate and analyze the general properties of this codependent growth. We discuss the general conditions for such growth and its applications to self-organization processes. PMID- 22320758 TI - Effect of the range of repulsions on the existence of a stable liquid phase. AB - Experimental and theoretical results have established that the range of the attraction plays a critical role in determining whether a particle system exhibits a stable liquid phase. Changes to the range of the repulsions can similarly affect the existence of a stable liquid phase; however, these effects have not been clearly elucidated. We demonstrate that an increase in the range of repulsions can either enhance or decrease the stability of the liquid phase, depending on the form of the interaction potential. For either case, the critical variable that controls the stability of the liquid phase is the ratio of the representative energies of the liquid and solid phases. PMID- 22320759 TI - Non-equilibrium umbrella sampling applied to force spectroscopy of soft matter. AB - Physical systems often respond on a timescale which is longer than that of the measurement. This is particularly true in soft matter where direct experimental measurement, for example in force spectroscopy, drives the soft system out of equilibrium and provides a non-equilibrium measure. Here we demonstrate experimentally for the first time that equilibrium physical quantities (such as the mean square displacement) can be obtained from non-equilibrium measurements via umbrella sampling. Our model experimental system is a bead fluctuating in a time-varying optical trap. We also show this for simulated force spectroscopy on a complex soft molecule--a piston-rotaxane. PMID- 22320760 TI - Effects of particles on stability of flow-induced precursors. AB - The effect of two colorant particles with different surface geometries on the stability of shear-induced precursors in isotactic polypropylene was studied after the cessation of shear flow at 140 degrees C. In the absence of particles, the shear-induced precursors survived for at least 100 s after the shear flow ended. The presence of particles was found to stabilize lower molecular weight chains assisting in the formation of additional shear-induced precursors. The precursors thus formed in the samples containing particles contained two oriented clusters with different molecular weights. Incorporation of lower molecular weight chains in the precursors led to increased dissolution rates of the shear induced precursors. Particle surface geometry was found to influence precursor dissolution, with planar particles stabilizing the shear-induced precursors to a much greater extent than curved particles. The particles investigated thus act like structural probes to follow quantitatively the dissolution process of precursors after shear and importantly to infer the formation of precursors during shear. PMID- 22320761 TI - Formation of dodecagonal quasicrystals in two-dimensional systems of patchy particles. AB - The behaviour of two-dimensional patchy particles with five and seven regularly arranged patches is investigated by computer simulation. For higher pressures and wider patch widths, hexagonal crystals have the lowest enthalpy, whereas at lower pressures and for narrower patches, lower density crystals with five nearest neighbours that are based on the (3(2),4,3,4) tiling of squares and triangles become lower in enthalpy. Interestingly, in regions of parameter space near to that where the hexagonal crystals become stable, quasicrystalline structures with dodecagonal symmetry form on cooling from high temperature. These quasicrystals can be considered as tilings of squares and triangles and are probably stabilized by the large configurational entropy associated with all the different possible such tilings. The potential for experimentally realizing such structures using DNA multi-arm motifs is also discussed. PMID- 22320762 TI - Conformational properties of macromolecular pyramoids and their potential use as nano-containers. AB - We study the macroscopic behavior of a pyramid-like nano-construct made of linear macromolecular chains. The average mean square end-to-end distances of the six edges of the pyramoid are evaluated by means of the Gaussian chain model and are found smaller than those of free chains because of architecture confinement. We also evaluate the average areas of the four faces which give a first estimate of the open windows towards the interior space of the macromolecular construct and its loading capacity. The average volume of the polymeric nano-container, which provides a measure of its interior emptiness and carrying ability, is estimated as well. The density of monomers at each point of the construct shows the three dimensional character of the nano-cage and the location of its entrances and voids. PMID- 22320763 TI - Combined depletion and electrostatic forces in polymer-induced membrane adhesion: a theoretical model. AB - We develop a semi-quantitative analytical theory to describe adhesion between two identical planar charged surfaces embedded in a polymer-containing electrolyte solution. Polymer chains are uncharged and differ from the solvent by their lower dielectric permittivity. The solution mimics physiological fluids: It contains 0.1 M of monovalent ions and a small number of divalent cations that form tight bonds with the headgroups of charged lipids. The components have heterogeneous spatial distributions. The model was derived self-consistently by combining: (a) a Poisson-Boltzmann like equation for the charge densities, (b) a continuum mean field theory for the polymer profile, (c) a solvation energy forcing the ions toward the polymer-poor regions, and (d) surface interactions of polymers and electrolytes. We validated the theory via extensive coarse-grained Molecular Dynamics (MD) simulations. The results confirm our analytical model and reveal interesting details not detected by the theory. At high surface charges, polymer chains are mainly excluded from the gap region, while the concentration of ions increases. The model shows a strong coupling between osmotic forces, surface potential and salting-out effects of the slightly polar polymer chains. It highlights some of the key differences in the behaviour of monomeric and polymeric mixed solvents and their responses to Coulomb interactions. Our main findings are: (a) the onset of long-ranged ion-induced polymer depletion force that increases with surface charge density and (b) a polymer-modified repulsive Coulomb force that increases with surface charge density. Overall, the system exhibits homeostatic behaviour, resulting in robustness against variations in the amount of charges. Applications and extensions of the model are briefly discussed. PMID- 22320764 TI - Correlated intermolecular coupling fluctuations in photosynthetic complexes. AB - The functioning and efficiency of natural photosynthetic complexes is strongly influenced by their embedding in a noisy protein environment, which can even serve to enhance the transport efficiency. Interactions with the environment induce fluctuations of the transition energies and couplings between the chlorophyll molecules, and due to the fact that different fluctuations will partially be caused by the same environmental factors, correlations between the various fluctuations will occur. We argue that fluctuations of the couplings should, in general, not be neglected, as these have a considerable impact on population transfer rates, decoherence rates, and the efficiency of photosynthetic complexes. Furthermore, while correlations between transition energy fluctuations have been studied, we provide the first quantitative study of the effect of correlations between coupling fluctuations and transition energy fluctuations, and of correlations between the various coupling fluctuations. It is shown that these additional correlations typically lead to changes in interchromophore transfer rates and population oscillations and can lead to a limited enhancement of the light harvesting efficiency. PMID- 22320765 TI - Point/counterpoint: vendor provided machine data should never be used as a substitute for fully commissioning a linear accelerator. PMID- 22320766 TI - A method to estimate the effect of deformable image registration uncertainties on daily dose mapping. AB - PURPOSE: To develop a statistical sampling procedure for spatially-correlated uncertainties in deformable image registration and then use it to demonstrate their effect on daily dose mapping. METHODS: Sequential daily CT studies are acquired to map anatomical variations prior to fractionated external beam radiotherapy. The CTs are deformably registered to the planning CT to obtain displacement vector fields (DVFs). The DVFs are used to accumulate the dose delivered each day onto the planning CT. Each DVF has spatially-correlated uncertainties associated with it. Principal components analysis (PCA) is applied to measured DVF error maps to produce decorrelated principal component modes of the errors. The modes are sampled independently and reconstructed to produce synthetic registration error maps. The synthetic error maps are convolved with dose mapped via deformable registration to model the resulting uncertainty in the dose mapping. The results are compared to the dose mapping uncertainty that would result from uncorrelated DVF errors that vary randomly from voxel to voxel. RESULTS: The error sampling method is shown to produce synthetic DVF error maps that are statistically indistinguishable from the observed error maps. Spatially correlated DVF uncertainties modeled by our procedure produce patterns of dose mapping error that are different from that due to randomly distributed uncertainties. CONCLUSIONS: Deformable image registration uncertainties have complex spatial distributions. The authors have developed and tested a method to decorrelate the spatial uncertainties and make statistical samples of highly correlated error maps. The sample error maps can be used to investigate the effect of DVF uncertainties on daily dose mapping via deformable image registration. An initial demonstration of this methodology shows that dose mapping uncertainties can be sensitive to spatial patterns in the DVF uncertainties. PMID- 22320767 TI - Development of a pixelated GSO gamma camera system with tungsten parallel hole collimator for single photon imaging. AB - PURPOSE: In small animal imaging using a single photon emitting radionuclide, a high resolution gamma camera is required. Recently, position sensitive photomultiplier tubes (PSPMTs) with high quantum efficiency have been developed. By combining these with nonhygroscopic scintillators with a relatively low light output, a high resolution gamma camera can become useful for low energy gamma photons. Therefore, the authors developed a gamma camera by combining a pixelated Ce-doped Gd(2)SiO(5) (GSO) block with a high quantum efficiency PSPMT. METHODS: GSO was selected for the scintillator, because it is not hygroscopic and does not contain any natural radioactivity. An array of 1.9 mm * 1.9 mm * 7 mm individual GSO crystal elements was constructed. These GSOs were combined with a 0.1-mm thick reflector to form a 22 * 22 matrix and optically coupled to a high quantum efficiency PSPMT (H8500C-100 MOD8). The GSO gamma camera was encased in a tungsten gamma-ray shield with tungsten pixelated parallel hole collimator, and the basic performance was measured for Co-57 gamma photons (122 keV). RESULTS: In a two-dimensional position histogram, all pixels were clearly resolved. The energy resolution was ~15% FWHM. With the 20-mm thick tungsten pixelated collimator, the spatial resolution was 4.4-mm FWHM 40 mm from the collimator surface, and the sensitivity was ~0.05%. Phantom and small animal images were successfully obtained with our developed gamma camera. CONCLUSIONS: These results confirmed that the developed pixelated GSO gamma camera has potential as an effective instrument for low energy gamma photon imaging. PMID- 22320768 TI - Gap compensation during PET image reconstruction by constrained, total variation minimization. AB - PURPOSE: Positron emission tomography (PET) is a noninvasive molecular imaging tool with various clinical and preclinical applications. The polygonal structure of small-diameter PET scanners that are designed for specific purposes can lead to gaps between the detector modules and result in loss of PET data during measurement. In the current study, the authors applied the compressed sensing (CS)-based total variation (TV) minimization method to PET image reconstructions to reduce the artifacts caused by gaps in small-diameter PET systems. METHODS: The first step in each iteration estimates whether an image is consistent with the measured PET data using the existing common reconstruction algorithms (ART, OSEM, and RAMLA). The second step recovers sparsity in the gradient domain of the image by minimizing the TV of an estimated image. The authors evaluated the gap compensable reconstruction algorithms with uniform disk and Shepp-Logan phantoms by simulating sinograms which contained Poisson random noise and a data loss due to detector gaps. In addition, these methods were applied to real high resolution research tomography (HRRT)-like sinograms of human brain and uniform phantom. A comparison with other methods for gap compensation prior to or during image reconstruction was also made. Quantitative evaluations were performed by computing the uniformity, root mean squared error, and difference between the reconstructed images of nongapped and gapped sinograms. RESULTS: The simulation results showed that the gap-compensable methods incorporating TV minimization could control gap artifacts, as well as Poisson random noise. In particular, OSEM TV and RAMLA-TV showed distinct potential via the properties of convergence and robustness to different noise levels and gap angle. CONCLUSIONS: A TV minimization strategy incorporated into commonly used PET reconstruction algorithms was useful for reducing the occurrence of artifacts due to gaps between detector modules in small-diameter PET scanners. PMID- 22320769 TI - A filtered backprojection algorithm with characteristics of the iterative landweber algorithm. AB - PURPOSE: In order to eventually develop an analytical algorithm with noise characteristics of an iterative algorithm, this technical note develops a window function for the filtered backprojection (FBP) algorithm in tomography that behaves as an iterative Landweber algorithm. METHODS: Based on the formulation of the iterative Landweber algorithm, a frequency domain window function is derived for each iteration of the Landweber algorithm. The resultant window function has an index k, emulating the characteristics of the Landweber algorithm at the kth iteration. The window function is used to modify the ramp filter in the FBP algorithm. RESULTS: Computer simulations show that the windowed FBP algorithm with window function index k and the iterative Landweber algorithm iteration number k give similar reconstructions in terms of resolution and noise. CONCLUSIONS: Analytical FBP algorithms are able to provide similar results to the iterative Landweber algorithm if the ramp filter in the FBP algorithm is modified by a set of specially designed window functions. PMID- 22320770 TI - Measured and calculated K-fluorescence effects on the MTF of an amorphous selenium based CCD x-ray detector. AB - PURPOSE: Theoretical reasoning suggests that direct conversion digital x-ray detectors based upon photoconductive amorphous-selenium (a-Se) could attain very high values of the MTF (modulation transfer function) at spatial frequencies well beyond 20 cycles mm(-1). One of the fundamental factors affecting resolution loss, particularly at x-ray energies just above the K-edge of selenium (12.66 keV), is the K-fluorescence reabsorption mechanism, wherein energy can be deposited in the detector at locations laterally displaced from the initial x-ray interaction site. This paper compares measured MTF changes above and below the Se K-edge of a CCD based a-Se x-ray detector with theoretical expectations. METHODS: A prototype 25 MUm sampling pitch (Nyquist frequency = 20 cycles mm(-1), 200 MUm thick a-Se layer based x-ray detector, utilizing a specialized CCD readout device (200 * 400 area array), was used to make edge images with monochromatic x-rays above and below the K-edge of Se. A vacuum double crystal monochromator, exposed to polychromatic x-rays from a synchrotron, formed the monochromatic x-ray source. The monochromaticity of the x-rays was 99% or better. The presampling MTF was determined using the slanted edge method. The theory modeling the MTF performance of the detector includes the basic x-ray interaction physics in the a Se layer as well as effects related to the operation of the CCD and charge trapping at a blocking layer present at the CCD/a-Se interface. RESULTS: The MTF performance of the prototype a-Se CCD was reduced from the theoretical value prescribed by the basic Se x-ray interaction physics, principally by the presence of a blocking layer. Nevertheless, the K-fluorescence reduction in the MTF was observed, approximately as predicted by theory. For the CCD prototype detector, at five cycles mm(-1), there was a 14% reduction of the MTF, from a value of 0.7 below the K-edge of Se, to 0.6 just above the K-edge. CONCLUSIONS: The MTF of an a-Se x-ray detector has been measured using monochromatic x-rays above and below the K-edge of selenium. The MTF is poorer above the K-edge by an amount consistent with theoretical expectations. PMID- 22320771 TI - Detection and correction for EPID and gantry sag during arc delivery using cine EPID imaging. AB - PURPOSE: Electronic portal imaging devices (EPIDs) have been studied and used for pretreatment and in-vivo dosimetry applications for many years. The application of EPIDs for dosimetry in arc treatments requires accurate characterization of the mechanical sag of the EPID and gantry during rotation. Several studies have investigated the effects of gravity on the sag of these systems but each have limitations. In this study, an easy experiment setup and accurate algorithm have been introduced to characterize and correct for the effect of EPID and gantry sag during arc delivery. METHODS: Three metallic ball bearings were used as markers in the beam: two of them fixed to the gantry head and the third positioned at the isocenter. EPID images were acquired during a 360 degrees gantry rotation in cine imaging mode. The markers were tracked in EPID images and a robust in-house developed MATLAB code was used to analyse the images and find the EPID sag in three directions as well as the EPID + gantry sag by comparison to the reference gantry zero image. The algorithm results were then tested against independent methods. The method was applied to compare the effect in clockwise and counter clockwise gantry rotations and different source-to-detector distances (SDDs). The results were monitored for one linear accelerator over a course of 15 months and six other linear-accelerators from two treatment centers were also investigated using this method. The generalized shift patterns were derived from the data and used in an image registration algorithm to correct for the effect of the mechanical sag in the system. The Gamma evaluation (3%, 3 mm) technique was used to investigate the improvement in alignment of cine EPID images of a fixed field, by comparing both individual images and the sum of images in a series with the reference gantry zero image. RESULTS: The mechanical sag during gantry rotation was dependent on the gantry angle and was larger in the in-plane direction, although the patterns were not identical for various linear-accelerators. The reproducibility of measurements was within 0.2 mm over a period of 15 months. The direction of gantry rotation and SDD did not affect the results by more than 0.3 mm. Results of independent tests agreed with the algorithm within the accuracy of the measurement tools. When comparing summed images, the percentage of points with Gamma index <1 increased from 85.4% to 94.1% after correcting for the EPID sag, and to 99.3% after correction for gantry + EPID sag. CONCLUSIONS: The measurement method and algorithms introduced in this study use cine-images, are highly accurate, simple, fast, and reproducible. It tests all gantry angles and provides a suitable automatic analysis and correction tool to improve EPID dosimetry and perform comprehensive linac QA for arc treatments. PMID- 22320772 TI - Design and evaluation of an optically-tracked single-CCD laser range scanner. AB - PURPOSE: Acquisition of laser range scans of an organ surface has the potential to efficiently provide measurements of geometric changes to soft tissue during a surgical procedure. A laser range scanner design is reported here which has been developed to drive intraoperative updates to conventional image-guided neurosurgery systems. METHODS: The scanner is optically-tracked in the operating room with a multiface passive target. The novel design incorporates both the capture of surface geometry (via laser illumination) and color information (via visible light collection) through a single-lens onto the same charge-coupled device (CCD). The accuracy of the geometric data was evaluated by scanning a high precision phantom and comparing relative distances between landmarks in the scans with the corresponding ground truth (known) distances. The range-of-motion of the scanner with respect to the optical camera was determined by placing the scanner in common operating room configurations while sampling the visibility of the reflective spheres. The tracking accuracy was then analyzed by fixing the scanner and phantom in place, perturbing the optical camera around the scene, and observing variability in scan locations with respect to a tracked pen probe ground truth as the camera tracked the same scene from different positions. RESULTS: The geometric accuracy test produced a mean error and standard deviation of 0.25 +/- 0.40 mm with an RMS error of 0.47 mm. The tracking tests showed that the scanner could be tracked at virtually all desired orientations required in the OR set up, with an overall tracking error and standard deviation of 2.2 +/- 1.0 mm with an RMS error of 2.4 mm. There was no discernible difference between any of the three faces on the lasers range scanner (LRS) with regard to tracking accuracy. CONCLUSIONS: A single-lens laser range scanner design was successfully developed and implemented with sufficient scanning and tracking accuracy for image-guided surgery. PMID- 22320773 TI - Small animal PET scanner based on monolithic LYSO crystals: performance evaluation. AB - PURPOSE: The authors have developed a small animal Positron emission tomography (PET) scanner based on monolithic LYSO crystals coupled to multi-anode photomultiplier tubes (MA-PMTs). In this study, the authors report on the design, calibration procedure, and performance evaluation of a PET system that the authors have developed using this innovative nonpixelated detector design. METHODS: The scanner is made up of eight compact modules forming an octagon with an axial field of view (FOV) of 40 mm and a transaxial FOV of 80 mm diameter. In order to fully determine its performance, a recently issued National Electrical Manufacturers Association (NEMA) NU-4 protocol, specifically developed for small animal PET scanners, has been followed. By measuring the width of light distribution collected in the MA-PMT the authors are able to determine depth of interaction (DOI), thus making the proper identification of lines of response (LORs) with large incidence angles possible. PET performances are compared with those obtained with currently commercially available small animal PET scanners. RESULTS: At axial center when the point-like source is located at 5 mm from the radial center, the spatial resolution measured was 1.65, 1.80, and 1.86 mm full width at half maximum (FWHM) for radial, tangential, and axial image profiles, respectively. A system scatter fraction of 7.5% (mouse-like phantom) and 13% (rat like phantom) was obtained, while the maximum noise equivalent count rate (NECR) was 16.9 kcps at 12.7 MBq (0.37 MBq/ml) for mouse-like phantom and 12.8 kcps at 12.4 MBq (0.042 MBq/ml) for rat-like phantom The peak absolute sensitivity in the center of the FOV is 2% for a 30% peak energy window. Several animal images are also presented. CONCLUSIONS: The overall performance of our small animal PET is comparable to that obtained with much more complex crystal pixelated PET systems. Moreover, the new proposed PET produces high-quality images suitable for studies with small animals. PMID- 22320774 TI - XCOM intrinsic dimensionality for low-Z elements at diagnostic energies. AB - PURPOSE: To determine the intrinsic dimensionality of linear attenuation coefficients (LACs) from XCOM for elements with low atomic number (Z = 1-20) at diagnostic x-ray energies (25-120 keV). H(0) (q), the hypothesis that the space of LACs is spanned by q bases, is tested for various q-values. METHODS: Principal component analysis is first applied and the LACs are projected onto the first q principal component bases. The residuals of the model values vs XCOM data are determined for all energies and atomic numbers. Heteroscedasticity invalidates the prerequisite of i.i.d. errors necessary for bootstrapping residuals. Instead wild bootstrap is applied, which, by not mixing residuals, allows the effect of the non-i.i.d residuals to be reflected in the result. Credible regions for the eigenvalues of the correlation matrix for the bootstrapped LAC data are determined. If subsequent credible regions for the eigenvalues overlap, the corresponding principal component is not considered to represent true data structure but noise. If this happens for eigenvalues l and l + 1, for any l <= q, H(0) (q) is rejected. RESULTS: The largest value of q for which H(0) (q) is nonrejectable at the 5%-level is q = 4. This indicates that the statistically significant intrinsic dimensionality of low-Z XCOM data at diagnostic energies is four. CONCLUSIONS: The method presented allows determination of the statistically significant dimensionality of any noisy linear subspace. Knowledge of such significant dimensionality is of interest for any method making assumptions on intrinsic dimensionality and evaluating results on noisy reference data. For LACs, knowledge of the low-Z dimensionality might be relevant when parametrization schemes are tuned to XCOM data. For x-ray imaging techniques based on the basis decomposition method (Alvarez and Macovski, Phys. Med. Biol. 21, 733-744, 1976), an underlying dimensionality of two is commonly assigned to the LAC of human tissue at diagnostic energies. The finding of a higher statistically significant dimensionality thus raises the question whether a higher assumed model dimensionality (now feasible with the advent of multibin x ray systems) might also be practically relevant, i.e., if better tissue characterization results can be obtained. PMID- 22320775 TI - Dosimetry concepts for scanner quality assurance and tissue dose assessment in micro-CT. AB - PURPOSE: At present, no established methods exist for dosimetry in micro computed tomography (micro-CT). The purpose of this study was therefore to investigate practical concepts for both dosimetric scanner quality assurance and tissue dose assessment for micro-CT. METHODS: The computed tomography dose index (CTDI) was adapted to micro-CT and measurements of the CTDI both free in air and in the center of cylindrical polymethyl methacrylate (PMMA) phantoms of 20 and 32 mm diameter were performed in a 6 month interval with a 100 mm pencil ionization chamber calibrated for low tube voltages. For tissue dose assessment, z-profile measurements using thermoluminescence dosimeters (TLDs) were performed and both profile and CTDI measurements were compared to Monte Carlo (MC) dose calculations to validate an existing MC tool for use in micro-CT. The consistency of MC calculations and TLD measurements was further investigated in two mice cadavers. RESULTS: CTDI was found to be a reproducible quantity for constancy tests on the micro-CT system under study, showing a linear dependence on tube voltage and being by definition proportional to mAs setting and z-collimation. The CTDI measured free in air showed larger systematic deviations after the 6 month interval compared to the CTDI measured in PMMA phantoms. MC calculations were found to match CTDI measurements within 3% when using x-ray spectra measured at our micro-CT installation and better than 10% when using x-ray spectra calculated from semi-empirical models. Visual inspection revealed good agreement for all z profiles. The consistency of MC calculations and TLD measurements in mice was found to be better than 10% with a mean deviation of 4.5%. CONCLUSIONS: Our results show the CTDI implemented for micro-CT to be a promising candidate for dosimetric quality assurance measurements as it linearly reflects changes in tube voltage, mAs setting, and collimation used during the scan, encouraging further studies on a variety of systems. For tissue dose assessment, MC calculations offer an accurate and fast alternative to TLD measurements allowing for dose calculations specific to any geometry and scan protocol. PMID- 22320776 TI - Correction method for in-air output ratio for output variations occurring with changes in backscattered radiation. AB - PURPOSE: The in-air output ratio (S(c)) for a rectangular field is usually obtained using an equivalent square field formula. However, it is well-known that S(c) obtained using an equivalent square field formula differs slightly from the measured S(c). Though several correction methods have been suggested for the monitor-backscatter effect, the authors propose a more simple correction method for a rectangular field. METHODS: For rectangular fields and equivalent square fields, the authors assumed that the output variation was the product of six output variations for each backscattering area at the top of the collimator jaws, and the correction factor was the ratio of the output variation for a rectangular field to the output variation for an equivalent square field. The output variation was measured by using a telescope measurement. RESULTS: The differences between the measured and corrected S(c) ranged from -0.20% to 0.28% for symmetric rectangular fields by applying the correction factor to S(c) obtained using an equivalent square field formula. This correction method is also available for asymmetric rectangular fields. CONCLUSIONS: The authors propose a method to correct S(c) obtained using an equivalent square field formula, and a method to obtain the output variation for a field defined by collimator jaws. PMID- 22320777 TI - Retrieval boosted computer-aided diagnosis of clustered microcalcifications for breast cancer. AB - PURPOSE: The authors propose an image-retrieval based approach for case-adaptive classifier design in computer-aided diagnosis (CADx). The conventional approach in CADx is to first train a pattern-classifier based on a set of existing training samples and then apply this classifier to subsequent new cases. The purpose of this work is to improve the classification accuracy of a CADx classifier by making use of a set of known cases retrieved from a reference library that are similar to the case under consideration. METHODS: In the proposed approach, the authors will first apply image-retrieval to obtain a set of lesion images from a library of known cases that have similar image features to a case being diagnosed (i.e., query). These retrieved cases are then used to optimize a pattern-classifier toward boosting its classification accuracy on the query case. The basic idea is to put more emphasis on those cases that are similar to the query. The proposed approach is demonstrated first using a linear classifier and then extended to a nonlinear classifier induced by kernel principal component analysis. RESULTS: The proposed retrieval-driven approach was tested on a library of mammogram images from 1006 cases (646 benign and 360 malignant) obtained from multiple institutions and was demonstrated to yield significant improvement in classification performance. Measured by the area under the receiver operating characteristic curve (AUC), the case-adaptive approach could boost the classification performance of a linear classifier from AUC = 0.7415 to AUC = 0.7807; similar improvement was also obtained for a nonlinear classifier, with AUC boosted from 0.7527 to 0.7838. CONCLUSIONS: Use of additional cases from a reference library that have similar image features can improve the classification accuracy of a CADx classifier on a query case. It can even outperform retraining the classifier with all the cases from the entire reference library. This implies that cases with similar image features are more relevant in defining the local decision boundary of the CADx classifier around the query. PMID- 22320778 TI - Multicriteria VMAT optimization. AB - PURPOSE: To make the planning of volumetric modulated arc therapy (VMAT) faster and to explore the tradeoffs between planning objectives and delivery efficiency. METHODS: A convex multicriteria dose optimization problem is solved for an angular grid of 180 equi-spaced beams. This allows the planner to navigate the ideal dose distribution Pareto surface and select a plan of desired target coverage versus organ at risk sparing. The selected plan is then made VMAT deliverable by a fluence map merging and sequencing algorithm, which combines neighboring fluence maps based on a similarity score and then delivers the merged maps together, simplifying delivery. Successive merges are made as long as the dose distribution quality is maintained. The complete algorithm is called VMERGE. RESULTS: VMERGE is applied to three cases: a prostate, a pancreas, and a brain. In each case, the selected Pareto-optimal plan is matched almost exactly with the VMAT merging routine, resulting in a high quality plan delivered with a single arc in less than 5 min on average. CONCLUSIONS: VMERGE offers significant improvements over existing VMAT algorithms. The first is the multicriteria planning aspect, which greatly speeds up planning time and allows the user to select the plan, which represents the most desirable compromise between target coverage and organ at risk sparing. The second is the user-chosen epsilon optimality guarantee of the final VMAT plan. Finally, the user can explore the tradeoff between delivery time and plan quality, which is a fundamental aspect of VMAT that cannot be easily investigated with current commercial planning systems. PMID- 22320779 TI - Investigation of the spatial resolution of an online dose verification device. AB - PURPOSE: The aim of this work is to characterize a new online dose verification device, COMPASS transmission detector array (IBA Dosimetry, Schwarzenbruck, Germany). The array is composed of 1600 cylindrical ionization chambers of 3.8 mm diameter, separated by 6.5 mm center-to-center spacing, in a 40 * 40 arrangement. METHODS: The line spread function (LSF) of a single ion chamber in the detector was measured with a narrow slit collimator for a 6 MV photon beam. The 0.25 * 10 mm(2) slit was formed by two machined lead blocks. The LSF was obtained by laterally translating the detector in 0.25 mm steps underneath the slit over a range of 24 mm and taking a measurement at each step. This measurement was validated with Monte Carlo simulation using BEAMnrc and DOSXYZnrc. The presampling modulation transfer function (MTF), the Fourier transform of the line spread function, was determined and compared to calculated (Monte Carlo and analytical) MTFs. Two head-and-neck intensity modulated radiation therapy (IMRT) fields were measured using the device and were used to validate the LSF measurement. These fields were simulated with the BEAMnrc Monte Carlo model, and the Monte Carlo generated incident fluence was convolved with the 2D detector response function (derived from the measured LSF) to obtain calculated dose. The measured and calculated dose distributions were then quantitatively compared using chi-comparison criteria of 3% dose difference and 3 mm distance-to agreement for in-field points (defined as those above the 10% maximum dose threshold). RESULTS: The full width at half-maximum (FWHM) of the measured detector response for a single chamber is 4.3 mm, which is comparable to the chamber diameter of 3.8 mm. The pre-sampling MTF was calculated, and the resolution of one chamber was estimated as 0.25 lp/mm from the first zero crossing. For both examined IMRT fields, the chi-comparison between measured and calculated data show good agreement with 95.1% and 96.3% of in-field points below chi of 1.0 for fields 1 and 2, respectively (with an average chi of 0.29 for IMRT field 1 and 0.24 for IMRT field 2). CONCLUSIONS: The LSF for a new novel online detector has been measured at 6 MV using a narrow slit technique, and this measurement has been validated by Monte Carlo simulation. The detector response function derived from line spread function has been applied to recover measured IMRT fields. The results have shown that the device measures IMRT fields accurately within acceptable tolerance. PMID- 22320780 TI - A phantom evaluation of Sentinel(TM), a commercial laser/camera surface imaging system for patient setup verification in radiotherapy. AB - PURPOSE: The aim of this study is to investigate the performance of Sentinel(TM), a patient setup verification device based on a laser/camera system, when used on rigid-body phantoms. METHODS: The Sentinel system consists of a scanner unit, containing the laser and the camera, and surface-matching registration software. For the registration procedure, both a computed tomography (CT) and a Sentinel image can be used as a reference. Tests were performed on phantoms using an Elekta Synergy((r)) beam modulator Linac equipped with a cone beam CT (CBCT), a HexaPOD RT couch top, and an iViewGT portal imaging system. Experiments conducted in this study tested reproducibility of the Sentinel surface acquisition and of set-up procedure, accuracy in quantifying known phantom mispositioning, and compared Sentinel, CBCT, and portal imaging system performance. RESULTS: Reproducibility of surface acquisition and setup procedure was better than 0.5 mm and 0.5 degrees and 1 mm and 0.4 degrees , respectively. The system accuracy was better than 1 mm and 1 degrees when a Sentinel image was used as reference. A global worsening of Sentinel performance was observed using as reference an external surface extracted from CT study. This effect is probably due to small differences in considered surfaces, caused by different imaging modalities. The results obtained by testing the system on rigid phantoms were comparable to those obtained using CBCT and better than those obtained with conventional portal imaging systems. CONCLUSIONS: The Sentinel setup verification device is a reproducible and consistent system able to detect misalignments with accuracy better than 1 mm and 1 degrees . When tested on rigid body phantoms, Sentinel and CBCT performed similarly. When compared to portal imaging, both Sentinel and CBCT were more accurate. PMID- 22320781 TI - Methods for monitor-unit-preserving adaptation of intensity modulated arc therapy techniques to the daily target-A simple comparison. AB - PURPOSE: For fast adaptation of step and shoot intensity modulated radiotherapy (IMRT) plans, monitor units (MU)-preserving methods which modify only the segment shapes have been proposed in the literature. In this work, two such adaptation methods are applied to intensity modulated arc therapy (IMAT) and their results are compared to that of a newly optimized IMAT plan. METHODS: In a simplified cylindrically symmetric model, the organ at risk (OAR) is surrounded by the planning target volume (PTV). For the initial plan, a steep dose gradient is produced by variants of double arc (IMAT) plans. To simulate situations which require adaptation, the OAR radius and the inner PTV radius have been varied. One adaptation method (Warp) is based on a mesh spanned over structures identified within the beam's eye view (BEV). Changes to the structure projections warp the mesh. For the adaptation, the segment shapes are fixed to the mesh. The other method (2-Step) uses geometrical 3D information from the computed tomography (CT). For comparison, the objective function representing the dose to the PTV as well as the mean and the maximum dose to the OAR is used. RESULTS: For the narrow segments that compensate the underdosage in the PTV areas proximate to the OAR, the Warp method suggests contrary adaptation rules compared to the 2-Step method. In contrast to Warp, the 2-Step method approximates the behavior of a newly optimized plan and leads to better dose homogeneity in the clinical target volume (CTV) and the PTV, whilst simultaneously sparing the OAR. CONCLUSIONS: For minor changes associated with less steep dose gradients, both Warp and 2-Step methods are suitable. However, the 2-Step method should be preferred for more challenging cases, where steep dose gradients between the OAR and the concave PTV are needed. For considerable interfractional reductions of the gap between the OAR and the PTV, where especially steep dose gradients have to be generated, MU-preserving adaptation techniques are not adequate. In this case, narrower segments in the initial plan can be used to facilitate the adaptation. Otherwise, non-MU preserving adaptation methods have to be applied. Further work is needed to include clinical cases with more complex geometries and expand the methods to IMRT techniques. PMID- 22320782 TI - Prostate brachytherapy postimplant dosimetry: seed orientation and the impact of dosimetric anisotropy in stranded implants. AB - PURPOSE: In postimplant dosimetry for prostate brachytherapy, dose is commonly calculated using the TG-43 1D formalism, because seed orientations are difficult to determine from CT images, the current standard for the procedure. However, the orientation of stranded seeds soon after implantation is predictable, as these seeds tend to maintain their relative spacing, and orient themselves along the implant trajectory. The aim of this study was to develop a method for determining seed orientations from reconstructed strand trajectories, and to use this information to investigate the dosimetric impact of applying the TG-43 2D formalism to clinical postimplant analysis. METHODS: Using in-house software, the preplan to postimplant seed correspondence was determined for a cohort of 30 patients during routine day-0 CT-based postimplant dosimetry. All patients were implanted with stranded-seed trains. Spline curves were fit to each set of seeds composing a strand, with the requirement that the distance along the spline between seeds be equal to the seed spacing within the strand. The orientations of the seeds were estimated by the tangents to the spline at each seed centroid. Dose distributions were then determined using the 1D and 2D TG-43 formalisms. These were compared using the TG-137 recommended dose metrics for the prostate, prostatic urethra, and rectum. RESULTS: Seven hundred and sixty one strands were analyzed in total. Defining the z-axis to be cranial-positive and the x-axis to be left-lateral positive in the CT coordinate system, the average seed had an inclination of 21 degrees +/- 10 degrees and an azimuth of -81 degrees +/- 57 degrees . These values correspond to the average strand rising anteriorly from apex to base, approximately parallel to the midsagittal plane. Clinically minor but statistically significant differences in dose metrics were noted. Compared to the 2D calculation, the 1D calculation underestimated prostate V100 by 1.1% and D90 by 2.3 Gy, while overestimating V150 and V200 by 1.6% and 1.3%, respectively. Urethral and rectal dose quantifiers tended to be underestimated by the 1D calculation. The most pronounced differences were in the urethral D30 and rectal D2cc, which rose by 3.8 and 1.9 Gy, respectively, using the 2D calculation. The total volume of the 100% isodose region as a percentage of the prostate volume was found to increase by 0.4%. CONCLUSIONS: Stranded seeds in the supine patient are not oriented in a uniformly random manner, nor are they aligned along the axis of the CT scanner. Instead, this study identified a consistent anterior pitch that is likely attributable to differences in patient pose between implant and CT imaging. The angle of the ultrasound probe with respect to the patient during implant may have also been a contributing factor. The dose metrics derived using the 1D formalism were found to be within 2%, on average, of those derived using the 2D formalism. For greater accuracy, 2D dosimetry can be pursued using the strand-fitting method described in this work. If a 1D representation is used, integrating over the empirically determined seed orientation density reported here may be more appropriate than assuming that seed inclinations are distributed uniformly. PMID- 22320783 TI - Automated lung segmentation in digital chest tomosynthesis. AB - PURPOSE: The purpose of this study was to develop an automated lung segmentation method for computerized detection of lung nodules in digital chest tomosynthesis. METHODS: The authors collected 45 digital tomosynthesis scans and manually segmented reference lung regions in each scan to assess the performance of the method. The authors automated the technique by calculating the edge gradient in an original image for enhancing lung outline and transforming the edge gradient image to polar coordinate space. The authors then employed a dynamic programming technique to delineate outlines of the unobscured lungs in the transformed edge gradient image. The lung outlines were converted back to the original image to provide the final segmentation result. The above lung segmentation algorithm was first applied to the central reconstructed tomosynthesis slice because of the absence of ribs overlapping lung structures. The segmented lung in the central slice was then used to guide lung segmentation in noncentral slices. The authors evaluated the segmentation method by using (1) an overlap rate of lung regions, (2) a mean absolute distance (MAD) of lung borders, (3) a Hausdorff distance of lung borders between the automatically segmented lungs and manually segmented reference lungs, and (4) the fraction of nodules included in the automatically segmented lungs. RESULTS: The segmentation method achieved mean overlap rates of 85.7%, 88.3%, and 87.0% for left lungs, right lungs, and entire lungs, respectively; mean MAD of 4.8, 3.9, and 4.4 mm for left lungs, right lungs, and entire lungs, respectively; and mean Hausdorrf distance of 25.0 mm, 25.5 mm, and 30.1 mm for left lungs, right lungs, and entire lungs, respectively. All of the nodules inside the reference lungs were correctly included in the segmented lungs obtained with the lung segmentation method. CONCLUSIONS: The method achieved relatively high accuracy for lung segmentation and will be useful for computer aided detection of lung nodules in digital tomosynthesis. PMID- 22320784 TI - Comprehensive validation of computational fluid dynamics simulations of in-vivo blood flow in patient-specific cerebral aneurysms. AB - PURPOSE: Recently, image-based computational fluid dynamic (CFD) simulations have been proposed to investigate the local hemodynamics inside human cerebral aneurysms. It was suggested that the knowledge of the computed three-dimensional flow fields can be used to assist clinical risk assessment and treatment decision making. Therefore, it was desired to know the reliability of CFD for cerebral blood flow simulation, and be able to provide clinical feedback. However, the validations were not yet comprehensive as they lack either patient-specific boundary conditions (BCs) required for CFD simulations or quantitative comparison methods. METHODS: In this study, based on a recently proposed in-vitro quantitative CFD evaluation approach via virtual angiography, the CFD evaluation was extended from phantom to patient studies. In contrast to previous work, patient-specific blood flow rates obtained by transcranial color coded Doppler ultrasound measurements were used to impose CFD BCs. Virtual angiograms (VAs) were constructed which resemble clinically acquired angiograms (AAs). Quantitative measures were defined to thoroughly evaluate the correspondence of the detailed flow features between the AAs and the VAs, and thus, the reliability of CFD simulations. RESULTS: The proposed simulation pipeline provided a comprehensive validation method of CFD simulation for reproducing cerebral blood flow, with a focus on the aneurysm region. Six patient cases were tested and close similarities were found in terms of spatial and temporal variations of contrast agent (CA) distribution between AAs and VAs. For patient #1 to #5, discrepancies of less than 11% were found for the relative root mean square errors in time intensity curve comparisons from characteristic vasculature positions. For patient #6, where the CA concentration curve at vessel inlet cannot be directly extracted from the AAs and given as a BC, deviations about 20% were found. CONCLUSIONS: As a conclusion, the reliability of the CFD simulations was well confirmed. Besides, it was shown that the accuracy of CFD simulations was closely related to the input BCs. PMID- 22320785 TI - Technical note: determination of the optimized image processing and template matching techniques for a patient intrafraction motion monitoring system. AB - PURPOSE: In this work, the authors determine the optimal template matching method and selection of pixel data for use in a system for monitoring patient intrafraction motion. METHODS: The motion monitoring system is based on optical tracking of a marker block placed on the patient. The temporal resolution of the system was evaluated with a respiratory motion phantom. The phantom moved the marker with a peak-to-peak amplitude of 0.6-4.0 cm and a period of 1, 3, and 6 s. Three template matching methods were applied: Sum of squared difference (SSD), sum of absolute difference (SAD), and normalized cross-correlation (NCC) using each of four pixel color data schemes (RGB and gray level modified by one of three image processing steps). An in-house algorithm called auto region-of interest (AutoROI) automatically reset the marker detection region-of-interest to improve the calculation speed. RESULTS: RGB and gray level temporal resolutions were 54.22 +/- 10.81 (1 SD) s and 12.70 +/- 3.87 (1 SD) s, respectively. The temporal resolution when using SSD and SAD was higher than when using NCC. Positional accuracy was within 1 mm. Both values were within the tolerance specified by AAPM Task Group 142. To avoid misidentification of the marker, a threshold-based self-validation within the marker recognition system was implemented and was found to improve the tracking of motion with a high amplitude and short period. CONCLUSIONS: An intrafraction motion monitoring system using SSD or SAD and applied to gray pixel data can achieve high temporal resolution and positional accuracy. PMID- 22320786 TI - A novel technique to enable experimental validation of deformable dose accumulation. AB - PURPOSE: To propose a novel technique to experimentally validate deformable dose algorithms by measuring 3D dose distributions under the condition of deformation using deformable gel dosimeters produced by a novel gel fabrication method. METHOD: Five gel dosimeters, two rigid control gels and three deformable gels, were manufactured and treated with the same conformal plan that prescribed 400 cGy to the isocenter. The control gels were treated statically; the deformable gels were treated while being compressed by an actuation device to simulate breathing motion (amplitude of compression = 1, 1.5, and 2 cm, respectively; frequency = 16 rpm). Comparison between the dose measured by the control gels and the corresponding static dose distribution calculated in the treatment planning system (TPS) has determined the intrinsic dose measurement uncertainty of the gel dosimeters. Doses accumulated using MORFEUS, a biomechanical model based deformable registration and dose accumulation algorithm, were compared with the doses measured by the deformable gel dosimeters to verify the accuracy of MORFEUS using dose differences at each voxel as well as the gamma index test. Flexible plastic wraps were used to contain and protect the deformable gels from oxygen infiltration, which inhibits the gels' dose sensitizing ability. Since the wraps were imperfect oxygen barrier, dose comparison between MORFEUS and the deformable gels was performed only in the central region with a received dose of 200 cGy or above to exclude the peripheral region where oxygen penetration had likely affected dose measurements. RESULTS: Dose measured with the control gels showed that the intrinsic dose measurement uncertainty of the gel dosimeters was 11.8 cGy or 4.7% compared to the TPS. The absolute mean voxel-by-voxel dose difference between the accumulated dose and the dose measured with the deformable gels was 4.7 cGy (SD = 36.0 cGy) or 1.5% (SD = 13.4%) for the three deformable gels. The absolute mean vector distance between the 250, 300, 350, and 400 cGy isodose surfaces on the accumulated and measured distributions was 1.2 mm (SD < 1.5 mm). The gamma index test that used the dose measurement precision of the control gels as the dose difference criterion and 2 mm as the distance criterion was performed, and the average pass rate of the accumulated dose distributions for all three deformable gels was 92.7%. When the distance criterion was relaxed to 3 mm, the average pass rate increased to 96.9%. CONCLUSION: This study has proposed a novel technique to manufacture deformable volumetric gel dosimeters. By comparing the doses accumulated in MORFEUS and the doses measured with the dosimeters under the condition of deformation, the study has also demonstrated the potential of using deformable gel dosimetry to experimentally validate algorithms that include deformations into dose computation. Since dose less than 200 cGy was not evaluated in this study, future investigations will focus more on low dose regions by either using bigger gel dosimeters or prescribing a lower dose to provide a more complete experimental validation of MORFEUS across a wider dose range. PMID- 22320787 TI - Use of internal scintillator radioactivity to calibrate DOI function of a PET detector with a dual-ended-scintillator readout. AB - PURPOSE: Positron emission tomography (PET) detectors that use a dual-ended scintillator readout to measure depth-of-interaction (DOI) must have an accurate DOI function to provide the relationship between DOI and signal ratios to be used for detector calibration and recalibration. In a previous study, the authors used a novel and simple method to accurately and quickly measure DOI function by irradiating the detector with an external uniform flood source; however, as a practical concern, implementing external uniform flood sources in an assembled PET system is technically challenging and expensive. In the current study, therefore, the authors investigated whether the same method could be used to acquire DOI function from scintillator-generated (i.e., internal) radiation. The authors also developed a method for calibrating the energy scale necessary to select the events within the desired energy window. METHODS: The authors measured the DOI function of a PET detector with lutetium yttrium orthosilicate (LYSO) scintillators. Radiation events originating from the scintillators' internal Lu 176 beta decay were used to measure DOI functions which were then compared with those measured from both an external uniform flood source and an electronically collimated external point source. The authors conducted these studies with several scintillators of differing geometries (1.5 * 1.5 and 2.0 * 2.0 mm(2) cross-section area and 20, 30, and 40 mm length) and various surface finishes (mirror-finishing, saw-cut rough, and other finishes in between), and in a prototype array. RESULTS: All measured results using internal and external radiation sources showed excellent agreement in DOI function measurement. The mean difference among DOI values for all scintillators measured from internal and external radiation sources was less than 1.0 mm for different scintillator geometries and various surface finishes. CONCLUSIONS: The internal radioactivity of LYSO scintillators can be used to accurately measure DOI function in PET detectors, regardless of scintillator geometry or surface finish. Because an external radiation source is not needed, this method of DOI function measurement can be practically applied to individual PET detectors as well as assembled systems. PMID- 22320788 TI - Magnetic shielding investigation for a 6 MV in-line linac within the parallel configuration of a linac-MR system. AB - PURPOSE: In our current linac-magnetic resonance (MR) design, a 6 MV in-line linac is placed along the central axis of the MR's magnet where the MR's fringe magnetic fields are parallel to the overall electron trajectories in the linac waveguide. Our previous study of this configuration comprising a linac-MR SAD of 100 cm and a 0.5 T superconducting (open, split) MR imager. It showed the presence of longitudinal magnetic fields of 0.011 T at the electron gun, which caused a reduction in target current to 84% of nominal. In this study, passive and active magnetic shielding was investigated to recover the linac output losses caused by magnetic deflections of electron trajectories in the linac within a parallel linac-MR configuration. METHODS: Magnetic materials and complex shield structures were used in a 3D finite element method (FEM) magnetic field model, which emulated the fringe magnetic fields of the MR imagers. The effects of passive magnetic shielding was studied by surrounding the electron gun and its casing with a series of capped steel cylinders of various inner lengths (26.5 306.5 mm) and thicknesses (0.75-15 mm) in the presence of the fringe magnetic fields from a commercial MR imager. In addition, the effects of a shield of fixed length (146.5 mm) with varying thicknesses were studied against a series of larger homogeneous magnetic fields (0-0.2 T). The effects of active magnetic shielding were studied by adding current loops around the electron gun and its casing. The loop currents, separation, and location were optimized to minimize the 0.011 T longitudinal magnetic fields in the electron gun. The magnetic field solutions from the FEM model were added to a validated linac simulation, consisting of a 3D electron gun (using OPERA-3d/scala) and 3D waveguide (using comsol Multiphysics and PARMELA) simulations. PARMELA's target current and output phase-space were analyzed to study the linac's output performance within the magnetic shields. RESULTS: The FEM model above agreed within 1.5% with the manufacturer supplied fringe magnetic field isoline data. When passive magnetic shields are used, the target current is recoverable to greater than 99% of nominal for shield thicknesses greater than 0.75 mm. The optimized active shield which resulted in 100% target current recovery consists of two thin current rings 110 mm in diameter with 625 and 430 A-turns in each ring. With the length of the passive shield kept constant, the thickness of the shield had to be increased to achieve the same target current within the increased longitudinal magnetic fields. CONCLUSIONS: A >=99% original target current is recovered with passive shield thicknesses >0.75 mm. An active shield consisting of two current rings of diameter of 110 mm with 625 and 430 A-turns fully recovers the loss that would have been caused by the magnetic fields. The minimal passive or active shielding requirements to essentially fully recover the current output of the linac in our parallel-configured linac-MR system have been determined and are easily achieved for practical implementation of the system. PMID- 22320789 TI - Technical note: spatial resolution of proton tomography: impact of air gap between patient and detector. AB - PURPOSE: Proton radiography and tomography were investigated since the early 1970s because of its low radiation dose, high density resolution, and ability to image directly proton stopping power. However, spatial resolution is still a limiting factor. In this note, preliminary results of the impact of an air gap between detector system and patient on spatial resolution are presented. METHODS: Spatial resolution of proton radiography and tomography is governed by multiple Coulomb scattering (MCS) of the protons in the patient. In this note, the authors employ Monte Carlo simulations of protons traversing a 20 cm thick water box. Entrance and exit proton coordinate measurements were simulated for improved spatial resolution. The simulations were performed with and without a 5 cm air gap in front of and behind the patient. Loss of spatial resolution due to the air gap was studied for protons with different initial angular confusion. RESULTS: It was found that spatial resolution is significantly deteriorated when a 5 cm air gap between the position sensitive detector and the patient is included. For a perfect parallel beam spatial resolution worsens by about 40%. Spatial resolution is getting worse with increasing angular confusion and can reach 80%. CONCLUSIONS: When proton radiographies are produced by measuring the entrance and exit coordinates of the protons in front of and behind the patient the air gap between the detector and the patient can significantly deteriorate the spatial resolution of the system by up to 80%. An alternative would be to measure in addition to the coordinates also the exit and entrance angles of each proton. In principle, using the air gap size and proton angle, images can be reconstructed with the same spatial resolution than without air gap. PMID- 22320790 TI - Spectral analysis of mammographic images using a multitaper method. AB - PURPOSE: Power spectral analysis in radiographic images is conventionally performed using a windowed overlapping averaging periodogram. This study describes an alternative approach using a multitaper technique and compares its performance with that of the standard method. This tool will be valuable in power spectrum estimation of images, whose content deviates significantly from uniform white noise. The performance of the multitaper approach will be evaluated in terms of spectral stability, variance reduction, bias, and frequency precision. The ultimate goal is the development of a useful tool for image quality assurance. METHODS: A multitaper approach uses successive data windows of increasing order. This mitigates spectral leakage allowing one to calculate a reduced-variance power spectrum. The multitaper approach will be compared with the conventional power spectrum method in several typical situations, including the noise power spectra (NPS) measurements of simulated projection images of a uniform phantom, NPS measurement of real detector images of a uniform phantom for two clinical digital mammography systems, and the estimation of the anatomic noise in mammographic images (simulated images and clinical mammograms). RESULTS: Examination of spectrum variance versus frequency resolution and bias indicates that the multitaper approach is superior to the conventional single taper methods in the prevention of spectrum leakage and variance reduction. More than four times finer frequency precision can be achieved with equivalent or less variance and bias. CONCLUSIONS: Without any shortening of the image data length, the bias is smaller and the frequency resolution is higher with the multitaper method, and the need to compromise in the choice of regions of interest size to balance between the reduction of variance and the loss of frequency resolution is largely eliminated. PMID- 22320791 TI - Physical evaluation of a needle photostimulable phosphor based CR mammography system. AB - PURPOSE: Needle phosphor based computed radiography (CR) systems promise improved image quality compared to powder phosphor based CR units for x-ray screening mammography. This paper compares the imaging performance of needle CR cassettes, powder based CR cassettes and a well established amorphous selenium (a-Se) based flat panel based mammography system, using consistent beam qualities. METHODS: Detector performance was assessed using modulation transfer function (MTF), normalized noise power spectrum (NNPS), and detective quantum efficiency (DQE). Mammography system performance was assessed against levels from the European Guidelines, including threshold gold thickness (c-d), relative signal difference to noise (SdNR) and mean glandular dose, for automatic exposure control settings suggested by the manufacturers. The needle based Agfa HM5.0 CR detector was compared against the single sided readout Agfa MM3.0R and dual sided readout Fuji Profect CS powder CR plates using a 28 kV Mo/Rh spectrum, while a 28 kV W/Rh spectrum was used to compare the Agfa HM5.0 against the Siemens MAMMOMAT Inspiration a-Se based system. RESULTS: MTF at 5 mm(-1) was 0.16 and 0.24 for the needle CR detector in the fast and slow scan directions, respectively, indicating a slight improvement (~20%) over the two powder CR systems but remained 50% lower than the result at 5 mm(-1) for the a-Se detector (~0.55). Structured screen noise was lower for the needle phosphor compared to the powder plates. CR system gain, estimated from the measured absorption fraction and NNPS results, was 6.3 for the (single sided) needle phosphor and 5.1 and 7.2 for the single sided and dual sided powder phosphor systems. Peak DQE at ~100 MUGy was 0.47 for the needle system compared to peak DQE figures of 0.33 and 0.46 for the single sided readout powder plates and dual sided readout plates. The high frequency DQE (at 5 mm(-1)) was 0.19 for the needle CR plates, a factor of approximately 3 greater than for the powder CR plates. At 28 kV W/Rh, 2 mm Al, peak DQE for the needle CR system was 0.45 against a value of 0.50 for the a-Se detector. The needle CR detector reached the Acceptable limit for 0.1 mm details in the European Guidelines at a mean glandular dose (MGD) of approximately 1.31 mGy imaged at 28 kV Mo/Rh, compared to figures of 2.19 and 1.43 mGy for the single sided and dual sided readout powder CR systems. The a-Se detector could reach the limit at 0.65 mGy using a 28 kV W/Rh spectrum, while the needle CR system required 1.09 mGy for the same spectrum. CONCLUSIONS: Imaging performance for the needle CR phosphor technology, characterized using MTF and DQE and threshold gold thickness demonstrated a clear improvement compared to both single and dual sided reading powder phosphor based CR systems. PMID- 22320792 TI - Empirical cupping correction for CT scanners with primary modulation (ECCP). AB - PURPOSE: X-ray CT measures the attenuation of polychromatic x-rays through an object. The raw data acquired, which are the negative logarithm of the relative x ray intensity behind the patient, must undergo water precorrection to linearize the measurement and to convert them into line integrals that are ready for reconstruction. The function to linearize the measured projection data depends on the detected spectrum of the ray. This spectrum may vary as a function of the detector position, e.g., in cases where the heel effect becomes relevant, where a bow-tie filter introduces channel-dependent beam hardening, or where a primary modulator is used to modulate the primary intensity of the spectrum. METHODS: The authors propose a new approach that allows to handle these effects in a highly convenient way. Their new empirical cupping correction for primary modulation (ECCP) corrects for artifacts, such as cupping artifacts or ring artifacts, which are induced by nonlinearities in the projection data due to spatially varying pre or postfiltration of the x-rays. To do so, ECCP requires only a simple scan of a homogeneous phantom of nearly arbitrary shape. Based on this information, coefficients of a polynomial series are calculated and stored for later use. RESULTS: Physical measurements demonstrate the quality of the precorrection that can be achieved using ECCP to remove the cupping artifacts and to obtain well calibrated CT values even in cases of strong primary modulation. A combination of ECCP with analytical techniques yielding a hybrid cupping correction method is possible and allows for channel-dependent correction functions. CONCLUSION: The proposed ECCP method is a very effective and easy to incorporate approach that compensates for even strong detector channel-dependent changes of the detected spectrum. (c) 2011 American Association of Physicists in Medicine. PMID- 22320793 TI - Ex vivo evaluation of a coherent normalization procedure to quantify in vivo finger strontium XRS measurements. AB - PURPOSE: Energy dispersive x-ray fluorescence spectroscopy (XRS) measurements were performed on human cadaver index fingers to measure bone strontium content in the presence of intact overlying soft-tissue. This work assesses the feasibility of applying a normalization procedure including soft-tissue correction of x-ray absorption as a means to quantify an ex vivo bone strontium XRS measurement. METHODS: Bone strontium measurements were made using an excitation-detection system incorporating an (125)I x-ray excitation source and an Ortec(r) Ametek-AMT Si(Li) detector in 180 degrees backscatter geometry. Spectral processing was accomplished using an in-house nonlinear least-squares Marquardt fitting routine. Bone strontium was quantified using an egs5 Monte Carlo based x-ray soft-tissue correction algorithm in conjunction with the normalization of strontium x-rays to the coherent scatter peaks of 35.5 keV (125)I gamma-rays. RESULTS: Comparison of tissue intact and bare bone finger XRS measurement quantification attempts revealed an overall discrepancy of 18.6% that is attributed primarily to the significant contribution of soft-tissue to coherent scatter of 35.5 keV source gamma-rays and to a lesser degree, inconsistencies with the simulated tissue correction model. Work toward the beginnings of an experimentally derived tissue correction model, as a means to validate the simulated model, have been reported. Two observations hinted at a systematic inflation of the observed Kbeta peak area. First, strontium concentrations estimated by Kalpha peak areas were less than the Kbeta peak areas by 28.6% (p < 0.0001) and 10.5% (p < 0.001) for tissue intact and bare bone measurements, respectively. Second, the Kalpha:Kbeta x-ray average ratios between tissue corrected (3.61 +/- 0.55) and bare bone predicted (4.4 +/- 0.4) did not agree (p < 0.0001) and pointed to shortcomings with the current processing treatment of strontium K x-ray peak area extraction. Through finger bone XRS measurements, bone strontium concentration in the Caucasian population was estimated at 95 +/- 15 MUg Sr/g dry bone. CONCLUSIONS: The discrepancies observed: between quantification attempts of tissue corrected and bare bone measurements, the inflated estimates of Kbeta relative to Kalpha peak concentrations and between observed and expected Kalpha:Kbeta ratios, have indicated that shortcomings with the bone strontium coherent normalization and tissue correction procedure exist. Coherent scatter contribution of soft-tissue overlying bone, tissue correction model limitations, and spectra processing issues are all mentioned as sources of observed discrepancies. PMID- 22320794 TI - Characteristics of Gafchromic XRQA2 films for kV image dose measurement. AB - PURPOSE: In this study, the relevant characteristics of the new Gafchromic XRQA2 film for its application in measuring kV cone beam computed tomography (CBCT) image doses were thoroughly investigated. METHODS: The film was calibrated free in air to air kerma levels between 0 and 9 cGy using 120 kVp photon beams produced by the x-ray volume imager. Films were scanned using transmission and reflection scanning modes with the Epson Expression 10000 XL flat-bed document scanner. The impact of film size, region of interest for the analysis, scan uniformity, scan resolution, scan orientation and alternate scanning sides on the analysis process were investigated. Energy dependence, postirradiation growth of reflectance with time and irradiation angular dependence of the film were tested at different air kerma levels. RESULTS: The net reflectance changed by ~3% when the size of the film piece changed from 1 cm * 2 cm to 10 cm * 11 cm and changed by ~1% when ROI changed from 0. 7 cm * 0. 7 cm to 8 cm * 8 cm, suggesting a good uniformity of the film. The film was successfully analyzed using the transmission scanning mode, calibration curves from both transmission and reflection scanning modes showed similar behavior. The calibration uncertainty was somewhat lower when the film was scanned using reflection mode (6% and 8% for reflection and transmission modes, respectively.) Higher scanning resolution came with increasing calibration uncertainty. The calibration uncertainty for reflection and transmission modes increased from ~3.5% to 7% and from ~3.5% to 9%, respectively when scanning resolution was changed from 50 to 400 dpi. Scanning the film on alternate sides using transmission mode led to variation of 16%-19% in the net optical density at doses commonly used for CBCT procedures. The film response changed by almost 10% when it was exposed to beams of two different energies (100 and 120 kVp.) Other features of the film such as film orientation, postexposure growth, and irradiation angular dependence were also investigated. CONCLUSIONS: The size of film piece and analysis ROI used for calibration slightly affected the film response. Both transmission and reflection scanning modes can be used to analyze the Gafchromic XRQA2, with the reflection mode having a somewhat lower calibration uncertainty. Scanning films on alternate sides using transmission mode significantly affects the optical density. The film response was shown to be energy dependent. The films reached stability in about 6 h after exposure. The film response was proven to be independent of irradiation angle except when the beam is parallel to the film surface. PMID- 22320795 TI - Three-dimensional lung tumor segmentation from x-ray computed tomography using sparse field active models. AB - PURPOSE: Manual segmentation of lung tumors is observer dependent and time consuming but an important component of radiology and radiation oncology workflow. The objective of this study was to generate an automated lung tumor measurement tool for segmentation of pulmonary metastatic tumors from x-ray computed tomography (CT) images to improve reproducibility and decrease the time required to segment tumor boundaries. METHODS: The authors developed an automated lung tumor segmentation algorithm for volumetric image analysis of chest CT images using shape constrained Otsu multithresholding (SCOMT) and sparse field active surface (SFAS) algorithms. The observer was required to select the tumor center and the SCOMT algorithm subsequently created an initial surface that was deformed using level set SFAS to minimize the total energy consisting of mean separation, edge, partial volume, rolling, distribution, background, shape, volume, smoothness, and curvature energies. RESULTS: The proposed segmentation algorithm was compared to manual segmentation whereby 21 tumors were evaluated using one-dimensional (1D) response evaluation criteria in solid tumors (RECIST), two-dimensional (2D) World Health Organization (WHO), and 3D volume measurements. Linear regression goodness-of-fit measures (r(2) = 0.63, p < 0.0001; r(2) = 0.87, p < 0.0001; and r(2) = 0.96, p < 0.0001), and Pearson correlation coefficients (r = 0.79, p < 0.0001; r = 0.93, p < 0.0001; and r = 0.98, p < 0.0001) for 1D, 2D, and 3D measurements, respectively, showed significant correlations between manual and algorithm results. Intra-observer intraclass correlation coefficients (ICC) demonstrated high reproducibility for algorithm (0.989-0.995, 0.996-0.997, and 0.999-0.999) and manual measurements (0.975-0.993, 0.985-0.993, and 0.980-0.992) for 1D, 2D, and 3D measurements, respectively. The intra-observer coefficient of variation (CV%) was low for algorithm (3.09%-4.67%, 4.85%-5.84%, and 5.65%-5.88%) and manual observers (4.20%-6.61%, 8.14%-9.57%, and 14.57%-21.61%) for 1D, 2D, and 3D measurements, respectively. CONCLUSIONS: The authors developed an automated segmentation algorithm requiring only that the operator select the tumor to measure pulmonary metastatic tumors in 1D, 2D, and 3D. Algorithm and manual measurements were significantly correlated. Since the algorithm segmentation involves selection of a single seed point, it resulted in reduced intra-observer variability and decreased time, for making the measurements. PMID- 22320796 TI - Automated detection of mass lesions in dedicated breast CT: a preliminary study. AB - PURPOSE: To develop an automated method to detect breast masses on dedicated breast CT (BCT) volumes and to conduct a preliminary evaluation of its performance. This method can be used in a computer-aided detection (CADe) system for noncontrast enhanced BCT. METHODS: The database included patient images, which were acquired under an IRB-approved protocol. The database in this study consisted of 132 cases. 50 cases contained 58 malignant masses, and 23 cases contained 24 benign masses. 59 cases did not contain any biopsy-proven lesions. Each case consisted of an unenhanced CT volume of a single breast. First, each breast was segmented into adipose and glandular tissues using a fuzzy c-means clustering algorithm. The glandular breast regions were then sampled at a resolution of 2 mm. At each sampling step, a 3.5-cm(3) volume-of-interest was subjected to constrained region segmentation and 17 characteristic features were extracted, yielding 17 corresponding feature volumes. Four features were selected using step-wise feature selection and merged with linear discriminant analysis trained in the task of distinguishing between normal breast glandular regions and masses. Detection performance was measured using free-response receiver operating characteristic analysis (FROC) with leave-one-case-out evaluation. RESULTS: The feature selection stage selected features that characterized the shape and margin strength of the segmented region. CADe sensitivity per case was 84% (std = 4.2%) at 2.6 (std = 0.06) false positives per volume, or 6 * 10(-3) per slice (at an average of 424 slices per volume in this data set). CONCLUSIONS: This preliminary study demonstrates the feasibility of our approach for CADe for BCT. PMID- 22320797 TI - Electron contamination modeling and skin dose in 6 MV longitudinal field MRIgRT: Impact of the MRI and MRI fringe field. AB - PURPOSE: In recent times, longitudinal field MRI-linac systems have been proposed for 6 MV MRI-guided radiotherapy (MRIgRT). The magnetic field is parallel with the beam axis and so will alter the transport properties of any electron contamination particles. The purpose of this work is to provide a first investigation into the potential effects of the MR and fringe magnetic fields on the electron contamination as it is transported toward a phantom, in turn, providing an estimate of the expected patient skin dose changes in such a modality. METHODS: Geant4 Monte Carlo simulations of a water phantom exposed to a 6 MV x-ray beam were performed. Longitudinal magnetic fields of strengths between 0 and 3 T were applied to a 30 * 30 * 20 cm(3) phantom. Surrounding the phantom there is a region where the magnetic field is at full MRI strength, consistent with clinical MRI systems. Beyond this the fringe magnetic field entering the collimation system is also modeled. The MRI-coil thickness, fringe field properties, and isocentric distance are varied and investigated. Beam field sizes of 5 * 5, 10 * 10, 15 * 15 and 20 * 20 cm(2) were simulated. Central axis dose, 2D virtual entry skin dose films, and 70 MUm skin depth doses were calculated using high resolution scoring voxels. RESULTS: In the presence of a longitudinal magnetic field, electron contamination from the linear accelerator is encouraged to travel almost directly toward the patient surface with minimal lateral spread. This results in a concentration of electron contamination within the x-ray beam outline. This concentration is particularly encouraged if the fringe field encompasses the collimation system. Skin dose increases of up to 1000% were observed for certain configurations and increases above Dmax were common. In nonmagnetically shielded cases, electron contamination generated from the jaw faces and air column is trapped and propagated almost directly to the phantom entry region, giving rise to intense dose hot spots inside the x-ray treatment field. These range up to 1000% or more of Dmax at the CAX, depending on field size, isocenter, and coil thickness. In the case of a fully magnetically shielded collimation system and the lowest MRI field of 0.25 T, the entry skin dose is expected to increase to at least 40%, 50%, 65%, and 80% of Dmax for 5 * 5, 10 * 10, 15 * 15, and 20 * 20 cm(2), respectively. CONCLUSIONS: Electron contamination from the linac head and air column may cause considerable skin dose increases or hot spots at the beam central axis on the entry side of a phantom or patient in longitudinal field 6 MV MRIgRT. This depends heavily on the properties of the magnetic fringe field entering the linac beam collimation system. The skin dose increase is also related to the MRI-coil thickness, the fringe field, and the isocenter distance of the linac. The results of this work indicate that the properties of the MRI fringe field, electron contamination production, and transport must be considered carefully during the design stage of a longitudinal MRI-linac system. PMID- 22320798 TI - A procedure to determine the planar integral spot dose values of proton pencil beam spots. AB - PURPOSE: Planar integral spot dose (PISD) of proton pencil beam spots (PPBSs) is a required input parameter for beam modeling in some treatment planning systems used in proton therapy clinics. The measurement of PISD by using commercially available large area ionization chambers, like the PTW Bragg peak chamber (BPC), can have large uncertainties due to the size limitation of these chambers. This paper reports the results of our study of a novel method to determine PISD values from the measured lateral dose profiles and peak dose of the PPBS. METHODS: The PISDs of 72.5, 89.6, 146.9, 181.1, and 221.8 MeV energy PPBSs were determined by area integration of their planar dose distributions at different depths in water. The lateral relative dose profiles of the PPBSs at selected depths were measured by using small volume ion chambers and were investigated for their angular anisotropies using Kodak XV films. The peak spot dose along the beam's central axis (D(0)) was determined by placing a small volume ion chamber at the center of a broad field created by the superposition of spots at different locations. This method allows eliminating positioning uncertainties and the detector size effect that could occur when measuring it in single PPBS. The PISD was then calculated by integrating the measured lateral relative dose profiles for two different upper limits of integration and then multiplying it with corresponding D(0). The first limit of integration was set to radius of the BPC, namely 4.08 cm, giving PISD(RBPC). The second limit was set to a value of the radial distance where the profile dose falls below 0.1% of the peak giving the PISD(full). The calculated values of PISD(RBPC) obtained from area integration method were compared with the BPC measured values. Long tail dose correction factors (LTDCFs) were determined from the ratio of PISD(full)/PISD(RBPC) at different depths for PPBSs of different energies. RESULTS: The spot profiles were found to have angular anisotropy. This anisotropy in PPBS dose distribution could be accounted in a reasonable approximate manner by taking the average of PISD values obtained using the in-line and cross-line profiles. The PISD(RBPC) values fall within 3.5% of those measured by BPC. Due to inherent dosimetry challenges associated with PPBS dosimetry, which can lead to large experimental uncertainties, such an agreement is considered to be satisfactory for validation purposes. The PISD(full) values show differences ranging from 1 to 11% from BPC measured values, which are mainly due to the size limitation of the BPC to account for the dose in the long tail regions of the spots extending beyond its 4.08 cm radius. The dose in long tail regions occur both for high energy beams such as 221.8 MeV PPBS due to the contributions of nuclear interactions products in the medium, and for low energy PPBS because of their larger spot sizes. The calculated LTDCF values agree within 1% with those determined by the Monte Carlo (MC) simulations. CONCLUSIONS: The area integration method to compute the PISD from PPBS lateral dose profiles is found to be useful both to determine the correction factors for the values measured by the BPC and to validate the results from MC simulations. PMID- 22320799 TI - Estimation of the weighted CTDI(infinity) for multislice CT examinations. AB - PURPOSE: The aim of this study was to examine the variations of CT dose index (CTDI) efficiencies, epsilon(CTDI(100))=CTDI(100)/CTDI(infinity), with bowtie filters and CT scanner types. METHODS: This was an extension of our previous study [Li, Zhang, and Liu, Phys. Med. Biol. 56, 5789-5803 (2011)]. A validated Monte Carlo program was used to calculate epsilon(CTDI(100)) on a Siemens Somatom Definition scanner. The epsilon(CTDI(100)) dependencies on tube voltages and beam widths were tested in previous studies. The influences of different bowtie filters and CT scanner types were examined in this work. The authors tested the variations of epsilon(CTDI(100)) with bowtie filters on the Siemens Definition scanner. The authors also analyzed the published CTDI measurements of four independent studies on five scanners of four models from three manufacturers. RESULTS: On the Siemens Definition scanner, the difference in epsilon(CTDI(W)) between using the head and body bowtie filters was 2.5% (maximum) in the CT scans of the 32-cm phantom, and 1.7% (maximum) in the CT scans of the 16-cm phantom. Compared with CTDI(W), the weighted CTDI(infinity) increased by 30.5% (on average) in the 32-cm phantom, and by 20.0% (on average) in the 16-cm phantom. These results were approximately the same for 80-140 kV and 1-40 mm beam widths (4.2% maximum deviation). The differences in epsilon(CTDI(100)) between the simulations and the direct measurements of four previous studies were 1.3%-5.0% at the center/periphery of the 16-cm/32-cm phantom (on average). CONCLUSIONS: Compared with CTDI(vol), the equilibrium dose for large scan lengths is 30.5% higher in the 32-cm phantom, and is 20.0% higher in the 16-cm phantom. The relative increases are practically independent of tube voltages (80-140 kV), beam widths (up to 4 cm), and the CT scanners covered in this study. PMID- 22320800 TI - Adaptation of a clustered lumpy background model for task-based image quality assessment in x-ray phase-contrast mammography. AB - PURPOSE: Since the introduction of clinical x-ray phase-contrast mammography (PCM), a technique that exploits refractive-index variations to create edge enhancement at tissue boundaries, a number of optimization studies employing physical image-quality metrics have been performed. Ideally, task-based assessment of PCM would have been conducted with human readers. These studies have been limited, however, in part due to the large parameter-space of PCM system configurations and the difficulty of employing expert readers for large scale studies. It has been proposed that numerical observers can be used to approximate the statistical performance of human readers, thus enabling the study of task-based performance over a large parameter-space. METHODS: Methods are presented for task-based image quality assessment of PCM images with a numerical observer, the most significant of which is an adapted lumpy background from the conventional mammography literature that accounts for the unique wavefield propagation physics of PCM image formation and will be used with a numerical observer to assess image quality. These methods are demonstrated by performing a PCM task-based image quality study using a numerical observer. This study employs a signal-known-exactly, background-known-statistically Bayesian ideal observer method to assess the detectability of a calcification object in PCM images when the anode spot size and calcification diameter are varied. RESULTS: The first realistic model for the structured background in PCM images has been introduced. A numerical study demonstrating the use of this background model has compared PCM and conventional mammography detection of calcification objects. The study data confirm the strong PCM calcification detectability dependence on anode spot size. These data can be used to balance the trade-off between enhanced image quality and the potential for motion artifacts that comes with use of a reduced spot size and increased exposure time. CONCLUSIONS: A method has been presented for the incorporation of structured breast background data into task-based numerical observer assessment of PCM images. The method adapts conventional background simulation techniques to the wavefield propagation physics necessary for PCM imaging. This method is demonstrated with a simple detection task. PMID- 22320801 TI - EBT2 film as a depth-dose measurement tool for radiotherapy beams over a wide range of energies and modalities. AB - PURPOSE: One of the fundamental parameters used for dose calculation is percentage depth-dose, generally measured employing ionization chambers. There are situations where use of ion chambers for measuring depth-doses is difficult or problematic. In such cases, radiochromic film might be an alternative. The EBT 2 model GAFCHROMICTM film was investigated as a potential tool for depth-dose measurement in radiotherapy beams over a broad range of energies and modalities. METHODS: Pieces of the EBT-2 model GAFCHROMICTM EBT2 film were exposed to x-ray, electron, and proton beams used in radiotherapy. The beams employed for this study included kilovoltage x-rays (75 kVp), (60)Co gamma-rays, megavoltage x-rays (18 MV), electrons (7 and 20 MeV), and pristine Bragg-peak proton beams (126 and 152 MeV). At each beam quality, film response was measured over the dose range of 0.4-8.0 Gy, which corresponds to optical densities ranging from 0.05 to 0.4 measured with a flat-bed document scanner. To assess precision in depth-dose measurements with the EBT-2 model GAFCHROMICTM film, uncertainty in measured optical density was investigated with respect to variation in film-to-film and scanner-bed uniformity. RESULTS: For most beams, percentage depth-doses measured with the EBT-2 model GAFCHROMICTM film show an excellent agreement with those measured with ion chambers. Some discrepancies are observed in case of (i) kilovoltage x-rays at larger depths due to beam-hardening, and (ii) proton beams around Bragg-peak due to quenching effects. For these beams, an empirical polynomial correction produces better agreement with ion-chamber data. CONCLUSIONS: The EBT-2 model GAFCHROMICTM film is an excellent secondary dosimeter for measurement of percentage depth-doses for a broad range of beam qualities and modalities used in radiotherapy. It offers an easy and efficient way to measure beam depth-dose data with a high spatial resolution. PMID- 22320802 TI - Clinical evaluations of an amplitude-based binning algorithm for 4DCT reconstruction in radiation therapy. AB - PURPOSE: Phase-binning algorithms are commonly utilized in 4DCT image reconstruction for characterization of tumor or organ shape and respiration motion, but breathing irregularities occurring during 4DCT acquisition can cause considerable image distortions. Recently, amplitude-binning algorithms have been evaluated as a potential improvement to phase-binning algorithms for 4DCT image reconstruction. The purpose of this study was to evaluate the performance of the first commercially available on-line retrospective amplitude-binning algorithm for comparison to the traditional phase-binning algorithm. METHODS: Both phantom and clinical data were used for evaluation. A phantom of known geometry was mounted on a 4D motion platform programmed with seven respiratory waves (two computer generated and five patient trajectories) and scanned with a Philips Brilliance Big bore 16-slice CT simulator. 4DCT images were reconstructed using commercial amplitude- and phase-binning algorithms. Image quality of the amplitude- and phase-binned image sets was compared by evaluation of shape and volume distortions in reconstructed images. Clinical evaluations were performed on 64 4DCT patient image sets in a blinded review process. The amplitude- and phase-binned 4DCT maximum intensity projection (MIP) images were further evaluated for 28 stereotactic body radiation therapy (SBRT) cases of total 64 cases. A preliminary investigation of the effects of respiratory amplitude and pattern irregularities on motion artifact severity was conducted. RESULTS: The phantom experiments illustrated that, as expected, maximum inhalation occurred at the 0% amplitude and maximum exhalation occurred at the 50% amplitude of the amplitude-binned 4DCT image sets. The phantom shape distortions were more severe in the images reconstructed from the phase-binning algorithm. In the clinical study, compared to the phase-binning algorithm, the amplitude-binning algorithm yielded fewer or less severe motion artifacts in 37.5% of the cases (24/64), comparable artifacts in 54.7% of the cases (35/64), and slightly greater artifacts in 7.8% of the cases (5/64). Evaluation of SBRT cases demonstrated that the reconstructed tumor sizes and locations were comparable in 96% (1/28) of the MIP image pairs generated from both amplitude- and phase-binning algorithms. In this case the amplitude-binned image set rendered a smaller tumor size, which was likely due to very shallow respiratory amplitudes occurring over several breathing cycles. CONCLUSIONS: Overall, the amplitude-binning algorithm for 4DCT reconstruction reduced the severity of tumor distortion and image artifacts compared to the phase-binning algorithm. However, the full range of motion may not be characterized using amplitude-binning algorithms. Despite superior performance, amplitude binning can still be susceptible to motion artifacts caused by large variations in amplitude of respiratory waves. PMID- 22320803 TI - Development of a semi-automated method for mitral valve modeling with medial axis representation using 3D ultrasound. AB - PURPOSE: Precise 3D modeling of the mitral valve has the potential to improve our understanding of valve morphology, particularly in the setting of mitral regurgitation (MR). Toward this goal, the authors have developed a user initialized algorithm for reconstructing valve geometry from transesophageal 3D ultrasound (3D US) image data. METHODS: Semi-automated image analysis was performed on transesophageal 3D US images obtained from 14 subjects with MR ranging from trace to severe. Image analysis of the mitral valve at midsystole had two stages: user-initialized segmentation and 3D deformable modeling with continuous medial representation (cm-rep). Semi-automated segmentation began with user-identification of valve location in 2D projection images generated from 3D US data. The mitral leaflets were then automatically segmented in 3D using the level set method. Second, a bileaflet deformable medial model was fitted to the binary valve segmentation by Bayesian optimization. The resulting cm-rep provided a visual reconstruction of the mitral valve, from which localized measurements of valve morphology were automatically derived. The features extracted from the fitted cm-rep included annular area, annular circumference, annular height, intercommissural width, septolateral length, total tenting volume, and percent anterior tenting volume. These measurements were compared to those obtained by expert manual tracing. Regurgitant orifice area (ROA) measurements were compared to qualitative assessments of MR severity. The accuracy of valve shape representation with cm-rep was evaluated in terms of the Dice overlap between the fitted cm-rep and its target segmentation. RESULTS: The morphological features and anatomic ROA derived from semi-automated image analysis were consistent with manual tracing of 3D US image data and with qualitative assessments of MR severity made on clinical radiology. The fitted cm-reps accurately captured valve shape and demonstrated patient-specific differences in valve morphology among subjects with varying degrees of MR severity. Minimal variation in the Dice overlap and morphological measurements was observed when different cm-rep templates were used to initialize model fitting. CONCLUSIONS: This study demonstrates the use of deformable medial modeling for semi-automated 3D reconstruction of mitral valve geometry using transesophageal 3D US. The proposed algorithm provides a parametric geometrical representation of the mitral leaflets, which can be used to evaluate valve morphology in clinical ultrasound images. PMID- 22320804 TI - iCycle: Integrated, multicriterial beam angle, and profile optimization for generation of coplanar and noncoplanar IMRT plans. AB - PURPOSE: To introduce iCycle, a novel algorithm for integrated, multicriterial optimization of beam angles, and intensity modulated radiotherapy (IMRT) profiles. METHODS: A multicriterial plan optimization with iCycle is based on a prescription called wish-list, containing hard constraints and objectives with ascribed priorities. Priorities are ordinal parameters used for relative importance ranking of the objectives. The higher an objective priority is, the higher the probability that the corresponding objective will be met. Beam directions are selected from an input set of candidate directions. Input sets can be restricted, e.g., to allow only generation of coplanar plans, or to avoid collisions between patient/couch and the gantry in a noncoplanar setup. Obtaining clinically feasible calculation times was an important design criterium for development of iCycle. This could be realized by sequentially adding beams to the treatment plan in an iterative procedure. Each iteration loop starts with selection of the optimal direction to be added. Then, a Pareto-optimal IMRT plan is generated for the (fixed) beam setup that includes all so far selected directions, using a previously published algorithm for multicriterial optimization of fluence profiles for a fixed beam arrangement Breedveld et al. [Phys. Med. Biol. 54, 7199-7209 (2009)]. To select the next direction, each not yet selected candidate direction is temporarily added to the plan and an optimization problem, derived from the Lagrangian obtained from the just performed optimization for establishing the Pareto-optimal plan, is solved. For each patient, a single one-beam, two-beam, three-beam, etc. Pareto-optimal plan is generated until addition of beams does no longer result in significant plan quality improvement. Plan generation with iCycle is fully automated. RESULTS: Performance and characteristics of iCycle are demonstrated by generating plans for a maxillary sinus case, a cervical cancer patient, and a liver patient treated with SBRT. Plans generated with beam angle optimization did better meet the clinical goals than equiangular or manually selected configurations. For the maxillary sinus and liver cases, significant improvements for noncoplanar setups were seen. The cervix case showed that also in IMRT with coplanar setups, beam angle optimization with iCycle may improve plan quality. Computation times for coplanar plans were around 1-2 h and for noncoplanar plans 4-7 h, depending on the number of beams and the complexity of the site. CONCLUSIONS: Integrated beam angle and profile optimization with iCycle may result in significant improvements in treatment plan quality. Due to automation, the plan generation workload is minimal. Clinical application has started. PMID- 22320805 TI - Automated teniae coli detection and identification on computed tomographic colonography. AB - PURPOSE: Computed tomographic colonography (CTC) is a minimally invasive technique for colonic polyps and cancer screening. Teniae coli are three bands of longitudinal smooth muscle on the colon surface. Teniae coli are important anatomically meaningful landmarks on human colon. In this paper, the authors propose an automatic teniae coli detection method for CT colonography. METHODS: The original CTC slices are first segmented and reconstructed to a 3D colon surface. Then, the 3D colon surface is unfolded using a reversible projection technique. After that the unfolded colon is projected to a 2D height map. The teniae coli are detected using the height map and then reversely projected back to the 3D colon. Since teniae are located at the junctions where the haustral folds meet, the authors apply 2D Gabor filter banks to extract features of haustral folds. The maximum response of the filter banks is then selected as the feature image. The fold centers are then identified based on local maxima and thresholding on the feature image. Connecting the fold centers yields a path of the folds. Teniae coli are extracted as lines running between the fold paths. The authors used the spatial relationship between ileocecal valve (ICV) and teniae mesocolica (TM) to identify the TM, then the teniae omentalis (TO) and the teniae libera (TL) can be identified subsequently. RESULTS: The authors tested the proposed method on 47 cases of 37 patients, 10 of the patients with both supine and prone CT scans. The proposed method yielded performance with an average normalized root mean square error (RMSE) ( +/- standard deviation [95% confidence interval]) of 4.87% ( +/- 2.93%, [4.05% 5.69%]). CONCLUSIONS: The proposed fully automated teniae coli detection and identification method is accurate and promising for future clinical applications. PMID- 22320806 TI - BEDVH-A method for evaluating biologically effective dose volume histograms: application to eye plaque brachytherapy implants. AB - PURPOSE: A method is introduced to examine the influence of implant duration T, radionuclide, and radiobiological parameters on the biologically effective dose (BED) throughout the entire volume of regions of interest for episcleral brachytherapy using available radionuclides. This method is employed to evaluate a particular eye plaque brachytherapy implant in a radiobiological context. METHODS: A reference eye geometry and 16 mm COMS eye plaque loaded with (103)Pd, (125)I, or (131)Cs sources were examined with dose distributions accounting for plaque heterogeneities. For a standardized 7 day implant, doses to 90% of the tumor volume ( (TUMOR)D(90)) and 10% of the organ at risk volumes ( (OAR)D(10)) were calculated. The BED equation from Dale and Jones and published alpha/beta and MU parameters were incorporated with dose volume histograms (DVHs) for various T values such as T = 7 days (i.e., (TUMOR) (7)BED(10) and (OAR) (7)BED(10)). By calculating BED throughout the volumes, biologically effective dose volume histograms (BEDVHs) were developed for tumor and OARs. Influence of T, radionuclide choice, and radiobiological parameters on (TUMOR)BEDVH and (OAR)BEDVH were examined. The nominal dose was scaled for shorter implants to achieve biological equivalence. RESULTS: (TUMOR)D(90) values were 102, 112, and 110 Gy for (103)Pd, (125)I, and (131)Cs, respectively. Corresponding (TUMOR) (7)BED(10) values were 124, 140, and 138 Gy, respectively. As T decreased from 7 to 0.01 days, the isobiologically effective prescription dose decreased by a factor of three. As expected, (TUMOR) (7)BEDVH did not significantly change as a function of radionuclide half-life but varied by 10% due to radionuclide dose distribution. Variations in reported radiobiological parameters caused (TUMOR) (7)BED(10) to deviate by up to 46%. Over the range of (OAR)alpha/beta values, (OAR) (7)BED(10) varied by up to 41%, 3.1%, and 1.4% for the lens, optic nerve, and lacrimal gland, respectively. CONCLUSIONS: BEDVH permits evaluation of the relative biological effectiveness for brachytherapy implants. For eye plaques, (TUMOR)BEDVH and (OAR)BEDVH were sensitive to implant duration, which may be manipulated to affect outcomes. PMID- 22320807 TI - Humidity effects on calibrations of radiation therapy electrometers. AB - PURPOSE: To eliminate variation in electrometer calibration results caused by high humidity and suboptimal connectors on the standard capacitors and to implement hardware that prevents overloading of the input stage of electrometers during calibration. METHODS: A humidity-controlled cabinet was installed to provide a low-humidity environment for the standard capacitors. All of the coaxial BNC connections were replaced with Triax (TRB) connectors with the exception of the output from the voltage source. A three-stage RC filter with cascaded RC low-pass sections was designed and tested. RESULTS: The installation of the humidity cabinet resulted in a major improvement in the stability and reproducibility of the electrometer calibration system. For the three years since this upgrade, the Ionizing Radiation Standards (IRS) electrometer calibration results have been consistent regardless of the ambient relative humidity in the lab. The connector replacements improved grounding in the calibration circuit. The three-stage filter allows the voltage at the output to rise in an S-shaped waveform, resulting in a smooth rise of the current through the isolation resistor from zero and back again, with no abrupt transition. For the filter design chosen, 99.99% of the charge is delivered within 6 s. CONCLUSIONS: A three way improvement to the calibration measurement system was successful in eliminating the observed variations, resulting in an electrometer calibration measurement system that is unaffected by humidity and allowing reliable year round calibrations of any electrometer encountered since the implementation of these changes. PMID- 22320808 TI - Quantitative classification based on CT histogram analysis of non-small cell lung cancer: correlation with histopathological characteristics and recurrence-free survival. AB - PURPOSE: Quantification of the CT appearance of non-small cell lung cancer (NSCLC) is of interest in a number of clinical and investigational applications. The purpose of this work is to present a quantitative five-category (alpha, beta, gamma, delta, and E) classification method based on CT histogram analysis of NSCLC and to determine the prognostic value of this quantitative classification. METHODS: Institutional review board approval and informed consent were obtained at the National Cancer Center Hospital. A total of 454 patients with NSCLC (maximum lesion size of 3 cm) were enrolled. Each lesion was measured using multidetector CT at the same tube voltage, reconstruction interval, beam collimation, and reconstructed slice thickness. Two observers segmented NSCLC nodules from the CT images by using a semi-automated three-dimensional technique. The two observers classified NSCLCs into one of five categories from the visual assessment of CT histograms obtained from each nodule segmentation result. Interobserver variability in the classification was computed with Cohen's kappa statistic. Any disagreements were resolved by consensus between the two observers to define the gold standard of the classification. Using a classification and regression tree (CART), the authors obtained a decision tree for a quantitative five-category classification. To assess the impact of the nodule segmentation on the classification, the variability in classifications obtained by two decision trees for the nodule segmentation results was also calculated with the Cohen's kappa statistic. The authors calculated the association of recurrence with prognostic factors including classification, sex, age, tumor diameter, smoking status, disease stage, histological type, lymphatic permeation, and vascular invasion using both univariate and multivariate Cox regression analyses. RESULTS: The kappa values for interobserver agreement of the classification using two nodule segmentation results were 0.921 (P < 0.001) and 0.903 (P < 0.001), respectively. The kappa values for the variability in the classification task using two decision trees were 0.981 (P < 0.001) and 0.981 (P < 0.001), respectively. All the NSCLCs were classified into one of five categories (type alpha, n = 8; type beta, n = 38; type gamma, n = 103; type delta, n = 112; type E, n = 193) by using a decision tree. Using a multivariate Cox regression analysis, the classification (hazard ratio 5.64; P = 0.008) and disease stage (hazard ratio 8.33; P < 0.001) were identified as being associated with an increased recurrence risk. CONCLUSIONS: The quantitative five-category classifier presented here has the potential to provide an objective classification of NSCLC nodules that is strongly correlated with prognostic factors. PMID- 22320809 TI - Gamma electron vertex imaging and application to beam range verification in proton therapy. AB - PURPOSE: This paper describes a new gamma-ray imaging method, "gamma electron vertex imaging (GEVI)," which can be used for precise beam range verification in proton therapy. METHODS: In GEVI imaging, the high-energy gammas from a source or nuclear interactions are first converted, by Compton scattering, to electrons, which subsequently are traced by hodoscopes to determine the location of the gamma source or the vertices of the nuclear interactions. The performance of GEVI imaging for use in-beam range verification was evaluated by Monte Carlo simulations employing geant4 equipped with the QGSP_BIC_HP physics package. RESULTS: Our simulation results show that GEVI imaging can determine the proton beam range very accurately, within 2-3 mm of error, even without any sophisticated analysis. The results were obtained under simplified conditions of monoenergetic pencil beams stopped in a homogeneous phantom and on the basis of the obtained results it is expected to achieve submillimeter accuracy in proton beam range measurement. CONCLUSIONS: If future experimental work confirms the simulated results presented in this paper, the use of GEVI imaging is expected to have a great potential in increasing the accuracy of proton beam range verification in a patient, resulting in significant improvement of treatment effectiveness by enabling tight conformation of radiation dose to the tumor volume and patient safety. PMID- 22320810 TI - Automated segmentation of a motion mask to preserve sliding motion in deformable registration of thoracic CT. AB - PURPOSE: Deformable registration generally relies on the assumption that the sought spatial transformation is smooth. Yet, breathing motion involves sliding of the lung with respect to the chest wall, causing a discontinuity in the motion field, and the smoothness assumption can lead to poor matching accuracy. In response, alternative registration methods have been proposed, several of which rely on prior segmentations. We propose an original method for automatically extracting a particular segmentation, called a motion mask, from a CT image of the thorax. METHODS: The motion mask separates moving from less-moving regions, conveniently allowing simultaneous estimation of their motion, while providing an interface where sliding occurs. The sought segmentation is subanatomical and based on physiological considerations, rather than organ boundaries. We therefore first extract clear anatomical features from the image, with respect to which the mask is defined. Level sets are then used to obtain smooth surfaces interpolating these features. The resulting procedure comes down to a monitored level set segmentation of binary label images. The method was applied to sixteen inhale exhale image pairs. To illustrate the suitability of the motion masks, they were used during deformable registration of the thorax. RESULTS: For all patients, the obtained motion masks complied with the physiological requirements and were consistent with respect to patient anatomy between inhale and exhale. Registration using the motion mask resulted in higher matching accuracy for all patients, and the improvement was statistically significant. Registration performance was comparable to that obtained using lung masks when considering the entire lung region, but the use of motion masks led to significantly better matching near the diaphragm and mediastinum, for the bony anatomy and for the trachea. The use of the masks was shown to facilitate the registration, allowing to reduce the complexity of the spatial transformation considerably, while maintaining matching accuracy. CONCLUSIONS: We proposed an automated segmentation method for obtaining motion masks, capable of facilitating deformable registration of the thorax. The use of motion masks during registration leads to matching accuracies comparable to the use of lung masks for the lung region but motion masks are more suitable when registering the entire thorax. PMID- 22320811 TI - Relationship between electron density and effective densities of body tissues for stopping, scattering, and nuclear interactions of proton and ion beams. AB - PURPOSE: In treatment planning of charged-particle radiotherapy, patient heterogeneity is conventionally modeled as variable-density water converted from CT images to best reproduce the stopping power, which may lead to inaccuracies in the handling of multiple scattering and nuclear interactions. Although similar conversions can be defined for these individual interactions, they would be valid only for specific CT systems and would require additional tasks for clinical application. This study aims to improve the practicality of the interaction specific heterogeneity correction. METHODS: The authors calculated the electron densities and effective densities for stopping power, multiple scattering, and nuclear interactions of protons and ions, using the standard elemental composition data for body tissues to construct the invariant conversion functions. The authors also simulated a proton beam in a lung-like geometry and a carbon-ion beam in a prostate-like geometry to demonstrate the procedure and the effects of the interaction-specific heterogeneity correction. RESULTS: Strong correlations were observed between the electron density and the respective effective densities, with which the authors formulated polyline conversion functions. Their effects amounted to 10% differences in multiple-scattering angle and nuclear interaction mean free path for bones compared to those in the conventional heterogeneity correction. Although their realistic effect on patient dose distributions would be generally small, it could be at the level of a few percent when a carbon-ion beam traverses a large bone. CONCLUSIONS: The present conversion functions are invariant and may be incorporated in treatment planning systems with a common function relating CT number to electron density. This will enable improved beam dose calculation while minimizing initial setup and quality management of the user's specific system. PMID- 22320812 TI - Impact of using linear optimization models in dose planning for HDR brachytherapy. AB - PURPOSE: Dose plans generated with optimization models hitherto used in high-dose rate (HDR) brachytherapy have shown a tendency to yield longer dwell times than manually optimized plans. Concern has been raised for the corresponding undesired hot spots, and various methods to mitigate these have been developed. The hypotheses upon this work is based are (a) that one cause for the long dwell times is the use of objective functions comprising simple linear penalties and (b) that alternative penalties, as these are piecewise linear, would lead to reduced length of individual dwell times. METHODS: The characteristics of the linear penalties and the piecewise linear penalties are analyzed mathematically. Experimental comparisons between the two types of penalties are carried out retrospectively for a set of prostate cancer patients. RESULTS: When the two types of penalties are compared, significant changes can be seen in the dwell times, while most dose-volume parameters do not differ significantly. On average, total dwell times were reduced by 4.2%, with a reduction of maximum dwell times by 25%, when the alternative penalties were used. CONCLUSIONS: The use of linear penalties in optimization models for HDR brachytherapy is one cause for the undesired long dwell times that arise in mathematically optimized plans. By introducing alternative penalties, a significant reduction in dwell times can be achieved for HDR brachytherapy dose plans. Although various measures for mitigating the long dwell times are already available, the observation that linear penalties contribute to their appearance is of fundamental interest. PMID- 22320813 TI - Quantitative accuracy of MAP reconstruction for dynamic PET imaging in small animals. AB - PURPOSE: Iterative reconstruction algorithms are becoming more commonly employed in positron emission tomography (PET) imaging; however, the quantitative accuracy of the reconstructed images still requires validation for various levels of contrast and counting statistics. METHODS: The authors present an evaluation of the quantitative accuracy of the 3D maximum a posteriori (3D-MAP) image reconstruction algorithm for dynamic PET imaging with comparisons to two of the most widely used reconstruction algorithms: the 2D filtered-backprojection (2D FBP) and 2D-ordered subsets expectation maximization (2D-OSEM) on the Siemens microPET scanners. The study was performed for various levels of count density encountered in typical dynamic scanning as well as the imaging of cardiac activity concentration in small animal studies on the Focus 120. Specially designed phantoms were used for evaluation of the spatial resolution, image quality, and quantitative accuracy. A normal mouse was employed to evaluate the accuracy of the blood time activity concentration extracted from left ventricle regions of interest (ROIs) within the images as compared to the actual blood activity concentration measured from arterial blood sampling. RESULTS: For MAP reconstructions, the spatial resolution and contrast have been found to reach a stable value after 20 iterations independent of the beta values (i.e., hyper parameter which controls the weight of the penalty term) and count density within the frame. The spatial resolution obtained with 3D-MAP reaches values of ~1.0 mm with a beta of 0.01 while the 2D-FBP has value of 1.8 mm and 2D-OSEM has a value of 1.6 mm. It has been observed that the lower the hyper parameter beta used in MAP, more iterations are needed to reach the stable noise level (i.e., image roughness). The spatial resolution is improved by using a lower beta value at the expense of higher image noise. However, with similar noise level the spatial resolution achieved by 3D-MAP was observed to be better than that by 2D-FBP or 2D OSEM. Using an image quality phantom containing hot spheres, the estimated activity concentration in the largest sphere has the expected concentration relative to the background area for all the MAP images. The obtained recovery coefficients have been also shown to be almost independent of the count density. 2D-FBP and 2D-OSEM do not perform as well, yielding recovery coefficients lower than those observed with 3D-MAP (approximately 33% lower for the smallest sphere). However, a small positive bias was observed in MAP reconstructed images for frames of very low count density. This bias is present in the uniform area for count density of less than 0.05 * 10(6) counts/ml. For the dynamic mouse study, it was observed that 3D-MAP (even gated at diastole) cannot predict accurately the blood activity concentration due to residual spill-over activity from the myocardium into the left ventricle (approximately 15%). However, 3D-MAP predicts blood activity concentration closer to blood sampling than 2D-FBP. CONCLUSIONS: The authors observed that 3D-MAP produces more accurate activity concentration estimates than 2D-FBP or 2D-OSEM at all practical levels of statistics and contrasts due to improved spatial resolution leading to lesser partial volume effect. PMID- 22320814 TI - Thoracic impedance change equation deduced on the basis of parallel impedance model and Ohm's law. AB - PURPOSE: The aim of the present study is to investigate an impedance change equation suited with the measurement of the impedance cardiograph (ICG). METHODS: Based on a parallel impedance model and Ohm's law, an impedance change equation differed from Nyboer's equation is deduced. It is verified with the experiments of the impedance cardiography in 100 healthy adults. RESULTS: This equation shows that the thoracic impedance change (DeltaZ) is directly proportional to the value of the volume change (DeltaV) of the blood vessel, to the ratio of the basic impedance to the body height (Z(0)/H), while it is inversely proportional to the square of the chest circumference (C(t) (2)). These are supported by the experimental results in the measurement of the ICG. CONCLUSIONS: The equation proposed in the present paper is coincident with the actual condition in the measurement of the ICG. PMID- 22320815 TI - The impact of audio-visual biofeedback on 4D PET images: results of a phantom study. AB - PURPOSE: Irregular breathing causes motion blurring artifacts in 4D PET images. Audiovisual (AV) biofeedback has been demonstrated to improve breathing regularity. To investigate the hypothesis that, compared with free breathing, motion blurring artifacts are reduced with AV biofeedback, the authors performed the first experimental phantom-based quantification of the impact of AV biofeedback on 4D PET image quality. METHODS: The authors acquired 4D PET dynamic phantom images with AV biofeedback and free breathing by moving a phantom programmed with AV biofeedback trained and free breathing respiratory traces of ten healthy subjects. The authors also acquired stationary phantom images for reference. The phantom was cylindrical with six hollow sphere targets (10, 13, 17, 22, 28, and 37 mm in diameter). The authors quantified motion blurring using the target diameter, Dice coefficient and recovery coefficient (RC) metrics to estimate the effect of motion. RESULTS: The average increase in target diameter for AV biofeedback was 0.6+/-1.6mm (4.7+/-13%), which was significantly (p<0.001) smaller than for free breathing 1.3+/-2.2mm (9.1+/-19%). The average Dice coefficient for AV biofeedback was 0.90+/-0.07, which was significantly (p<0.001) larger than for free breathing (0.88+/-0.10). The RCs for AV biofeedback were consistently higher than those for free breathing and comparable to those for stationary targets. However, for RCs the impact of target sizes was more dominant than that of motion. In addition, the authors observed large variations in the results with respect to target sizes, subject traces and respiratory bins due to partial volume effects and respiratory motion irregularity. CONCLUSIONS: The results indicate that AV biofeedback can significantly reduce motion blurring artifacts and may facilitate improved identification and localization of lung tumors in 4D PET images. The results justify proceeding with clinical studies to quantify the impact of AV biofeedback on 4D PET image quality and tumor detectability. PMID- 22320816 TI - Fast patient-specific Monte Carlo brachytherapy dose calculations via the correlated sampling variance reduction technique. AB - PURPOSE: To demonstrate potential of correlated sampling Monte Carlo (CMC) simulation to improve the calculation efficiency for permanent seed brachytherapy (PSB) implants without loss of accuracy. METHODS: CMC was implemented within an in-house MC code family (PTRAN) and used to compute 3D dose distributions for two patient cases: a clinical PSB postimplant prostate CT imaging study and a simulated post lumpectomy breast PSB implant planned on a screening dedicated breast cone-beam CT patient exam. CMC tallies the dose difference, DeltaD, between highly correlated histories in homogeneous and heterogeneous geometries. The heterogeneous geometry histories were derived from photon collisions sampled in a geometrically identical but purely homogeneous medium geometry, by altering their particle weights to correct for bias. The prostate case consisted of 78 Model-6711 (125)I seeds. The breast case consisted of 87 Model-200 (103)Pd seeds embedded around a simulated lumpectomy cavity. Systematic and random errors in CMC were unfolded using low-uncertainty uncorrelated MC (UMC) as the benchmark. CMC efficiency gains, relative to UMC, were computed for all voxels, and the mean was classified in regions that received minimum doses greater than 20%, 50%, and 90% of D(90), as well as for various anatomical regions. RESULTS: Systematic errors in CMC relative to UMC were less than 0.6% for 99% of the voxels and 0.04% for 100% of the voxels for the prostate and breast cases, respectively. For a 1 * 1 * 1 mm(3) dose grid, efficiency gains were realized in all structures with 38.1 and 59.8-fold average gains within the prostate and breast clinical target volumes (CTVs), respectively. Greater than 99% of the voxels within the prostate and breast CTVs experienced an efficiency gain. Additionally, it was shown that efficiency losses were confined to low dose regions while the largest gains were located where little difference exists between the homogeneous and heterogeneous doses. On an AMD 1090T processor, computing times of 38 and 21 sec were required to achieve an average statistical uncertainty of 2% within the prostate (1 * 1 * 1 mm(3)) and breast (0.67 * 0.67 * 0.8 mm(3)) CTVs, respectively. CONCLUSIONS: CMC supports an additional average 38-60 fold improvement in average efficiency relative to conventional uncorrelated MC techniques, although some voxels experience no gain or even efficiency losses. However, for the two investigated case studies, the maximum variance within clinically significant structures was always reduced (on average by a factor of 6) in the therapeutic dose range generally. CMC takes only seconds to produce an accurate, high-resolution, low uncertainly dose distribution for the low-energy PSB implants investigated in this study. PMID- 22320817 TI - Static and rotational step-and-shoot IMRT treatment plans for the prostate: a risk comparison study. AB - PURPOSE: For certain clinical applications, rotational intensity modulated radiation therapy (R-IMRT) techniques such as volumetric modulated arc therapy (VMAT) are capable of improved target dose coverage and shorter delivery time when compared to static, step-and-shoot IMRT. The authors performed a risk comparison study for two standard step-and-shoot IMRT plans and two step-and shoot Rotational IMRT plans that were designed specifically for a Siemens Primus linear accelerator. METHODS: CT images of a RANDO phantom were used to generate R IMRT and static IMRT plans. One simple and one complex prostate cases were created to investigate these techniques. The R-IMRT plans consisted of 72 single segmented 6 MV beams, equally spaced with beam angle separations of 5 degrees . The static IMRT plans employed seven multisegmented 6 MV beams. Both types of plans were optimized in Pinnacle(3) with the direct machine parameter optimization (DMPO) algorithm using the same set of optimization objectives. The plans were delivered to a RANDO phantom and thermoluminescent diode (TLD) dose measurements were performed at various locations throughout the phantom. Risk coefficients and organ weightings as defined by International Commission on Radiological Protection (ICRP) Publication 103 were used to calculate the resulting effective doses to various organs at risk, as well as the overall risk estimate for both techniques. RESULTS: For the simple prostate case, the R-IMRT technique provided a higher dose to organs at risk within the CT volume and a lower overall peripheral dose to remaining organs. The R-IMRT plan had a risk estimate of 4.56% when compared to the IMRT risk of 4.78%. For the complex prostate case, there was no significant difference in the lifetime risks of the IMRT (5.73%) and R-IMRT (5.74%) plans. CONCLUSIONS: R-IMRT is an approximation to VMAT and it was found that there is no clinically significant difference between lifetime risk estimates between R-IMRT and standard seven-beam IMRT for the prostate. PMID- 22320818 TI - Robust optimization of intensity modulated proton therapy. AB - PURPOSE: Intensity modulated proton therapy (IMPT) is highly sensitive to range uncertainties and uncertainties caused by setup variation. The conventional inverse treatment planning of IMPT optimized based on the planning target volume (PTV) is not often sufficient to ensure robustness of treatment plans. In this paper, a method that takes the uncertainties into account during plan optimization is used to mitigate the influence of uncertainties in IMPT. METHODS: The authors use the so-called "worst-case robust optimization" to render IMPT plans robust in the face of uncertainties. For each iteration, nine different dose distributions are computed-one each for +/- setup uncertainties along anteroposterior (A-P), lateral (R-L) and superior-inferior (S-I) directions, for +/- range uncertainty, and the nominal dose distribution. The worst-case dose distribution is obtained by assigning the lowest dose among the nine doses to each voxel in the clinical target volume (CTV) and the highest dose to each voxel outside the CTV. Conceptually, the use of worst-case dose distribution is similar to the dose distribution achieved based on the use of PTV in traditional planning. The objective function value for a given iteration is computed using this worst-case dose distribution. The objective function used has been extended to further constrain the target dose inhomogeneity. RESULTS: The worst-case robust optimization method is applied to a lung case, a skull base case, and a prostate case. Compared with IMPT plans optimized using conventional methods based on the PTV, our method yields plans that are considerably less sensitive to range and setup uncertainties. An interesting finding of the work presented here is that, in addition to reducing sensitivity to uncertainties, robust optimization also leads to improved optimality of treatment plans compared to the PTV-based optimization. This is reflected in reduction in plan scores and in the lower normal tissue doses for the same coverage of the target volume when subjected to uncertainties. CONCLUSIONS: The authors find that the worst-case robust optimization provides robust target coverage without sacrificing, and possibly even improving, the sparing of normal tissues. Our results demonstrate the importance of robust optimization. The authors assert that all IMPT plans should be robustly optimized. PMID- 22320819 TI - A pseudo-time EnKF incorporating shape based reconstruction for diffuse optical tomography. AB - PURPOSE: The authors aim at developing a pseudo-time, sub-optimal stochastic filtering approach based on a derivative free variant of the ensemble Kalman filter (EnKF) for solving the inverse problem of diffuse optical tomography (DOT) while making use of a shape based reconstruction strategy that enables representing a cross section of an inhomogeneous tumor boundary by a general closed curve. METHODS: The optical parameter fields to be recovered are approximated via an expansion based on the circular harmonics (CH) (Fourier basis functions) and the EnKF is used to recover the coefficients in the expansion with both simulated and experimentally obtained photon fluence data on phantoms with inhomogeneous inclusions. The process and measurement equations in the pseudo dynamic EnKF (PD-EnKF) presently yield a parsimonious representation of the filter variables, which consist of only the Fourier coefficients and the constant scalar parameter value within the inclusion. Using fictitious, low-intensity Wiener noise processes in suitably constructed "measurement" equations, the filter variables are treated as pseudo-stochastic processes so that their recovery within a stochastic filtering framework is made possible. RESULTS: In our numerical simulations, we have considered both elliptical inclusions (two inhomogeneities) and those with more complex shapes (such as an annular ring and a dumbbell) in 2-D objects which are cross-sections of a cylinder with background absorption and (reduced) scattering coefficient chosen as MU(a) (b)=0.01mm(-1) and MU(s) ('b)=1.0mm(-1), respectively. We also assume MU(a) = 0.02 mm(-1) within the inhomogeneity (for the single inhomogeneity case) and MU(a) = 0.02 and 0.03 mm(-1) (for the two inhomogeneities case). The reconstruction results by the PD EnKF are shown to be consistently superior to those through a deterministic and explicitly regularized Gauss-Newton algorithm. We have also estimated the unknown MU(a) from experimentally gathered fluence data and verified the reconstruction by matching the experimental data with the computed one. CONCLUSIONS: The PD EnKF, which exhibits little sensitivity against variations in the fictitiously introduced noise processes, is also proven to be accurate and robust in recovering a spatial map of the absorption coefficient from DOT data. With the help of shape based representation of the inhomogeneities and an appropriate scaling of the CH expansion coefficients representing the boundary, we have been able to recover inhomogeneities representative of the shape of malignancies in medical diagnostic imaging. PMID- 22320820 TI - Comparisons of treatment optimization directly incorporating systematic patient setup uncertainty with a margin-based approach. AB - PURPOSE: To develop a probabilistic treatment planning (PTP) method which is robust to systematic patient setup errors and to compare PTP plans with plans generated using a planning target volume (PTV) margin optimized to give the same target coverage probability as the PTP plan. METHODS: Plans adhering to the RTOG 0126 protocol are developed for 28 prostate patients using PTP and margin-based planning. For PTP, an objective function that simultaneously considers multiple possible patient positions is developed. PTP plans are optimized using clinical target volume (CTV) structures and organ at risk (OAR) structures. The desired CTV coverage probability is 95%. Plans that cannot achieve a 95% CTV coverage probability are re-optimized with a desired CTV coverage probability reduced by 5% until the desired CTV coverage probability is achieved. Margin-based plans are created which achieve the same CTV coverage probability as the PTP plans by iterative adjustment of the CTV-to-PTV margin. Postoptimization, probabilistic dose-volume coverage metrics are used to compare the plans. RESULTS: For equivalent target coverage probability, PTP plans significantly reduce coverage probability for rectum objectives (-17% for D(35) < 65 Gy, p = 0.0010; -23% for D(25) < 70 Gy, p < 0.0001; and -27% for D(15) < 75 Gy, p < 0.0001). Physician assessment indicates PTP plans are entirely preferred 71% of the time while margin-based plans are entirely preferred 7% of the time. CONCLUSIONS: For plans having the same target coverage probability, PTP has potential to reduce rectal doses while maintaining CTV coverage probability. In blind comparisons, physicians prefer PTP plans over optimized margin plans. PMID- 22320821 TI - Can volumetric modulated arc therapy with flattening filter free beams play a role in stereotactic body radiotherapy for liver lesions? A volume-based analysis. AB - PURPOSE: To compare volumetric modulated arc therapy with flattening filter free (FFF) and flattening filter (FF) beams in patients with hepatic metastases subject to hypofractionated radiotherapy (RT). METHODS: A planning study on 13 virtual lesions of increasing volume was performed. Two single arc plans were optimized with the RapidArc technique using either FFF or FF beams. A second planning study was performed on ten patients treated for liver metastases to validate conclusions. In all cases, a dose of 75 Gy in 3 fractions was prescribed to the planning target volume (PTV) and plans were evaluated in terms of coverage, homogeneity, conformity, mean dose to healthy liver and to healthy tissue. For each parameter, results were expressed in relative terms as the percentage ratio between FFF and FF data. RESULTS: In terms of PTV coverage, conformity index favored FFF for targets of intermediate size while FF resulted more suitable for small (<100 cm(3)) and large (>300 cm(3)) targets. Plans optimized with FFF beams resulted in increased sparing of healthy tissue in ~85% of cases. Despite the qualitative results, no statistically significant differences were found between FFF and FF results. Plans optimized with un flattened beams resulted in higher average MU/Gy than plans with FF beams. A remarkable and significant difference was observed in the beam-on time (BOT) needed to deliver plans. The BOT for FF plans was 8.2 +/- 1.0 min; for FFF plans BOT was 2.2 +/- 0.2 min. CONCLUSIONS: RapidArc plans optimized using FFF were dosimetrically equivalent to those optimized using FF beams, showing the feasibility of SBRT treatments with FFF beams. Some improvement in healthy tissue sparing was observed when using the FFF modality due to the different beam's profile. The main advantage was a considerable reduction of beam-on time, relevant for SBRT techniques. PMID- 22320822 TI - Irradiation of the prostate and pelvic lymph nodes with an adaptive algorithm. AB - PURPOSE: The simultaneous treatment of pelvic lymph nodes and the prostate in radiotherapy for prostate cancer is complicated by the independent motion of these two target volumes. In this work, the authors study a method to adapt intensity modulated radiation therapy (IMRT) treatment plans so as to compensate for this motion by adaptively morphing the multileaf collimator apertures and adjusting the segment weights. METHODS: The study used CT images, tumor volumes, and normal tissue contours from patients treated in our institution. An IMRT treatment plan was then created using direct aperture optimization to deliver 45 Gy to the pelvic lymph nodes and 50 Gy to the prostate and seminal vesicles. The prostate target volume was then shifted in either the anterior-posterior direction or in the superior-inferior direction. The treatment plan was adapted by adjusting the aperture shapes with or without re-optimizing the segment weighting. The dose to the target volumes was then determined for the adapted plan. RESULTS: Without compensation for prostate motion, 1 cm shifts of the prostate resulted in an average decrease of 14% in D-95%. If the isocenter is simply shifted to match the prostate motion, the prostate receives the correct dose but the pelvic lymph nodes are underdosed by 14% +/- 6%. The use of adaptive morphing (with or without segment weight optimization) reduces the average change in D-95% to less than 5% for both the pelvic lymph nodes and the prostate. CONCLUSIONS: Adaptive morphing with and without segment weight optimization can be used to compensate for the independent motion of the prostate and lymph nodes when combined with daily imaging or other methods to track the prostate motion. This method allows the delivery of the correct dose to both the prostate and lymph nodes with only small changes to the dose delivered to the target volumes. PMID- 22320823 TI - Metal artifact reduction for CT: development, implementation, and clinical comparison of a generic and a scanner-specific technique. AB - PURPOSE: To develop, implement, and compare two metal artifact reduction methods for CT. METHODS: Two methods for metal artifact reduction were developed. The first is based on applying corrections in a Radon transformation of the CT images. The second method is based on a forward projection of the CT images and applying corrections in the scanner's original raw data. The first method is generic since it does not depend on the scanner specifications. For the second method, detailed information on the design of the CT scanner and the raw data of the study is required. Clinical implementation and evaluation were performed using pre- and post-operative CT scans of four patients with shoulder prosthesis. For comparison of these methods, the authors developed a quantitative technique that compares improvement in image quality for the two metal artifact reduction techniques with the image quality of the uncorrected images. RESULTS: Metal artifact reduction using either of the two methods yields a decrease of noise and artifacts in CT scans of patients with shoulder prostheses. Artifacts that appeared as bright and dark streaks were reduced or eliminated and as a result image quality improved. Quantitative assessment of clinical images showed improved image quality for both techniques of metal artifact reduction, but the method based on correction in original raw data performed better in all comparisons. CONCLUSION: Both methods are effective for metal artifact reduction, but better performance was observed for the method that is based on correcting the original raw data. The used evaluation technique provides an objective way of evaluating the metal artifacts in clinical CT images. PMID- 22320824 TI - Determination of absorbed dose to water around a clinical HDR (192)Ir source using LiF:Mg,Ti TLDs demonstrates an LET dependence of detector response. AB - PURPOSE: Experimental radiation dosimetry with thermoluminescent dosimeters (TLDs), calibrated in a (60)Co or megavoltage (MV) photon beam, is recommended by AAPM TG-43U1for verification of Monte Carlo calculated absorbed doses around brachytherapy sources. However, it has been shown by Carlsson Tedgren et al. [Med. Phys. 38, 5539-5550 (2011)] that for TLDs of LiF:Mg,Ti, detector response was 4% higher in a (137)Cs beam than in a (60)Co one. The aim of this work was to investigate if similar over-response exists when measuring absorbed dose to water around (192)Ir sources, using LiF:Mg,Ti dosimeters calibrated in a 6 MV photon beam. METHODS: LiF dosimeters were calibrated to measure absorbed dose to water in a 6 MV photon beam and used to measure absorbed dose to water at distances of 3, 5, and 7 cm from a clinical high dose rate (HDR) (192)Ir source in a polymethylmethacrylate (PMMA) phantom. Measured values were compared to values of absorbed dose to water calculated using a treatment planning system (TPS) including corrections for the difference in energy absorption properties between calibration quality and the quality in the users' (192)Ir beam and for the use of a PMMA phantom instead of the water phantom underlying dose calculations in the TPS. RESULTS: Measured absorbed doses to water around the (192)Ir source were overestimated by 5% compared to those calculated by the TPS. Corresponding absorbed doses to water measured in a previous work with lithium formate electron paramagnetic resonance (EPR) dosimeters by Antonovic et al. [Med. Phys. 36, 2236 2247 (2009)], using the same irradiation setup and calibration procedure as in this work, were 2% lower than those calculated by the TPS. The results obtained in the measurements in this work and those obtained using the EPR lithium formate dosimeters were, within the expanded (k = 2) uncertainty, in agreement with the values derived by the TPS. The discrepancy between the results using LiF:Mg,Ti TLDs and the EPR lithium formate dosimeters was, however, statistically significant and in agreement with the difference in relative detector responses found for the two detector systems by Carlsson Tedgren et al. [Med. Phys. 38, 5539-5550 (2011)] and by Adolfsson et al. [Med. Phys. 37, 4946-4959 (2010)]. CONCLUSIONS: When calibrated in (60)Co or MV photon beams, correction for the linear energy transfer (LET) dependence of LiF:Mg,Ti detector response will be needed as to measure absorbed doses to water in a (192)Ir beam with highest accuracy. Such corrections will depend on the manufacturing process (MTS-N Poland or Harshaw TLD-100) and details of the annealing and read-out schemes used. PMID- 22320825 TI - MR-guided adaptive focusing of therapeutic ultrasound beams in the human head. AB - PURPOSE: This study aims to demonstrate, using human cadavers the feasibility of energy-based adaptive focusing of ultrasonic waves using magnetic resonance acoustic radiation force imaging (MR-ARFI) in the framework of non-invasive transcranial high intensity focused ultrasound (HIFU) therapy. METHODS: Energy based adaptive focusing techniques were recently proposed in order to achieve aberration correction. The authors evaluate this method on a clinical brain HIFU system composed of 512 ultrasonic elements positioned inside a full body 1.5 T clinical magnetic resonance (MR) imaging system. Cadaver heads were mounted onto a clinical Leksell stereotactic frame. The ultrasonic wave intensity at the chosen location was indirectly estimated by the MR system measuring the local tissue displacement induced by the acoustic radiation force of the ultrasound (US) beams. For aberration correction, a set of spatially encoded ultrasonic waves was transmitted from the ultrasonic array and the resulting local displacements were estimated with the MR-ARFI sequence for each emitted beam. A noniterative inversion process was then performed in order to estimate the spatial phase aberrations induced by the cadaver skull. The procedure was first evaluated and optimized in a calf brain using a numerical aberrator mimicking human skull aberrations. The full method was then demonstrated using a fresh human cadaver head. RESULTS: The corrected beam resulting from the direct inversion process was found to focus at the targeted location with an acoustic intensity 2.2 times higher than the conventional non corrected beam. In addition, this corrected beam was found to give an acoustic intensity 1.5 times higher than the focusing pattern obtained with an aberration correction using transcranial acoustic simulation-based on X-ray computed tomography (CT) scans. CONCLUSIONS: The proposed technique achieved near optimal focusing in an intact human head for the first time. These findings confirm the strong potential of energy-based adaptive focusing of transcranial ultrasonic beams for clinical applications. PMID- 22320826 TI - Comment on "QA procedures in radiation therapy are outdated and negatively impact the reduction of errors" [Med. Phys. 38, 5835 (2011)]. PMID- 22320829 TI - Validity and reliability of the Movement Assessment Battery for Children-2 Checklist for children with and without motor impairments. AB - AIM: The aim of this study was to investigate the validity and reliability of the Movement Assessment Battery for Children-2 Checklist (MABC-2). METHOD: Teachers completed the Checklist for 383 children (age range 5-8y; mean age 6y 9mo; 190 males; 193 females) and the parents of 130 of these children completed the Developmental Disorder Coordination Questionnaire 2007 (DCDQ'07). All children were assessed with the MABC-2 Test. The internal consistency of the 30 items of the Checklist was determined to measure reliability. Construct validity was investigated using factor analysis and discriminative validity was assessed by comparing the scores of children with and without movement difficulties. Concurrent validity was measured by calculating correlations between the Checklist, Test, and the DCDQ'07. Incremental validity was assessed to determine whether the Checklist was a better predictor of motor impairment than the DCDQ'07. Sensitivity and specificity were investigated using the MABC-2 Test as reference standard (cut-off 15th centile). RESULTS: The Checklist items measure the same construct. Six factors were obtained after factor analysis. This implies that a broad range of functional activities can be assessed with the Checklist, which renders the Checklist useful for assessing criterion B of the diagnostic criteria for DCD. The mean Checklist scores for children with and without motor impairments significantly differed (p<0.001). The scores for the Checklist/Test and DCDQ'07 were significantly correlated (r(S) =-0.38 and p<0.001, and r(S) = 0.36 and p<0.001, respectively). The Checklist better predicted motor impairment than the DCDQ'07. Overall, the sensitivity was low (41%) and the specificity was acceptable (88%). INTERPRETATION: The Checklist meets standards for validity and reliability. PMID- 22320830 TI - Pseudohypopyon as a clinical manifestation in metastatic lung carcinoma. AB - Pseudohypopyon is a rare clinical presentation of meta-static disease in the eye. The authors report a case of anterior chamber pseudohypopyon in a 74-year-old man with a history of primary central nervous system and spleen lymphoma, as well as lung, prostate, and bladder carcinoma. A diagnostic vitrectomy and anterior chamber paracentesis of the involved eye was performed that confirmed non-small cell carcinoma of lung primary. PMID- 22320831 TI - Retinal hemorrhages as a presenting sign of meningitis. AB - The association between retinal hemorrhages and meningitis has been previously documented; however, all of these cases were among critically ill patients with clinically progressive bacterial meningitis. This case report describes a patient with aseptic meningitis who presented with retinal hemorrhage. Physicians should consider meningitis in the work-up of patients presenting with retinal hemorrhage. PMID- 22320832 TI - High-penetration optical coherence tomography with enhanced depth imaging of polypoidal choroidal vasculopathy. AB - A combination of high-penetration spectral-domain optical coherence tomography (central wavelength: 1,020 nm) and an enhanced depth imaging protocol (HP-EDI OCT) was used to evaluate 5 eyes of 5 patients with polypoidal choroidal vasculopathy (PCV). In all eyes, HP-EDI-OCT provided high-contrast images of PCV lesions in the subretinal pigment epithelium (sub-RPE). In the space between the RPE line and Bruch's membrane, various PCV lesions, including vascular networks, polypoidal lesions, and sub-RPE hemorrhage, were clearly identified. The chorioscleral interface was clearly observed, and the entire structure of the choroid was readily identified. Thus, HP-EDI-OCT was useful for evaluating sub RPE lesions of PCV. PMID- 22320833 TI - tRNA ligase catalyzes the GTP-dependent ligation of RNA with 3'-phosphate and 5' hydroxyl termini. AB - The RNA ligase RtcB is conserved in all domains of life and is essential for tRNA maturation in archaea and metazoa. Here we show that bacterial and archaeal RtcB catalyze the GTP-dependent ligation of RNA with 3'-phosphate and 5'-hydroxyl termini. Reactions with analogues of RNA and GTP suggest a mechanism in which RtcB heals the 3'-phosphate terminus by forming a 2',3'-cyclic phosphate before joining it to the 5'-hydroxyl group of a second RNA strand. Thus, RtcB can ligate RNA cleaved by RNA endonucleases, which generate 2',3'-cyclic phosphate and then 3'-phosphate termini on one strand, and a 5'-hydroxyl terminus on another strand. PMID- 22320834 TI - Distinct distribution of killer-cell immunoglobulin-like receptor genes in the Mugil and Ilaita areas of Papua New Guinea. AB - The frequency of the killer-cell immunoglobulin-like receptor (KIR) genes and transmembrane alleles of KIR2DL4 were studied in coastal (Mugil community) and inland (Ilaita community) communities in Papua New Guinea. Linkage disequilibria between KIR genes and between alleles of KIR2DL4 and the KIR genes were similar to those found in other populations suggesting conservation of the usual gene order in Papua New Guinean haplotypes. Significant differences in the frequency of KIR genes were found between the two populations despite being separated by only 300 km. Examples of individuals who lacked the KIR2DL4 gene and others whose KIR2DL4 allele appeared to have 11 adenines in the polyadenine tract in exon 6 were identified. A relatively low frequency of the KIR A haplotype was found in both populations and particularly in the inland community. The KIR gene frequencies were consistent with the inland Ilaita community being closely related to Australian Aborigines and southern Indians, whereas the KIR gene frequencies of the coastal Mugil community appeared to have been influenced either by recent or ancient admixture from populations with a higher frequency of the KIR A haplotype. PMID- 22320835 TI - Adenovirus-mediated gene transfer of tissue factor pathway inhibitor-2 inhibits gallbladder carcinoma growth in vitro and in vivo. AB - Tissue factor pathway inhibitor-2 (TFPI-2) has been identified as a tumor suppressor gene in several types of cancers, but its role in gallbladder carcinoma (GBC) is yet to be determined. In the present study, TFPI-2 expression in GBC tissues was examined, and its inhibitory activities against GBC growth were evaluated in vitro and in vivo after adenovirus-mediated gene transfer of TFPI-2 (Ad5-TFPI-2) was constructed to restore the expression of TFPI-2 in GBC cell lines (GBC-SD, SGC-996, NOZ) and xenograft tumors. Immunohistochemical staining showed that TFPI-2 was significantly downregulated in GBC tissue specimens. Ad5-TFPI-2 could significantly inhibit GBC growth both in vitro and in vivo. Apoptosis analysis and western blotting assay demonstrated that Ad5-TFPI-2 could induce the apoptosis of both GBC cell lines and tissues by promoting the activities of cytochrome c, Bax, caspase-3 and -9 and suppressing Bcl-2 activity. These data indicated that TFPI-2 acts as a tumor suppressor in GBC, and may have a potential role in gene therapy for GBC. PMID- 22320836 TI - Cryopreservation of umbilical cord blood with a novel freezing solution that mimics intracellular ionic composition. AB - BACKGROUND: Cryopreservation protocols have remained relatively unchanged since the first umbilical cord blood banking program was established. This study evaluated the preservation efficacy of a novel intracellular-like cryopreservation solution (CryoStor, BioLife Solutions, Inc.), the rate of addition of two cryopreservation solutions to cord blood units (CBUs), and reduced final dimethyl sulfoxide (DMSO) concentration of 5%. STUDY DESIGN AND METHODS: Split-sample CBUs were cryopreserved with either an in-house 20% DMSO based cryopreservation solution or CryoStor CS10 at a rate of 1 mL/min (n = 10; i.e., slow addition) or as a bolus injection (n = 6; i.e., fast addition). Infrared images of exothermic effects of the cryopreservation solutions were monitored relative to the rate of addition. Prefreeze and postthaw colony-forming unit assays, total nucleated cells, and CD34+ cell counts were compared. RESULTS: Maximum temperature excursions observed were less than 6 degrees C, regardless of the rate of solution addition. Fast addition resulted in peak excursions approximately twice that of slow addition but the magnitude and duration were minimal and transient. Slow addition of CryoStor CS10 (i.e., final concentration <= 5% DMSO) resulted in significantly better postthaw CD34+ cell recoveries; no other metrics were significantly different. Fast addition of CryoStor resulted in similar postthaw metrics compared to slow addition of the in-house solution. CONCLUSION: Slow and fast addition of cryopreservation solutions result in mean temperature changes of approximately 3.3 to 4.45 degrees C. Postthaw recoveries with CryoStor were equivalent to or slightly better than with the in-house cryopreservation solution. CryoStor also provides several advantages including reduced processing time, formulation consistency, and reduced DMSO in the frozen product (<= 5%). PMID- 22320837 TI - Overweight and obesity in twenty-year-old Swedes in relation to birthweight and weight development during childhood. AB - AIM: To describe the frequency of overweight and obesity from birth to 20 years of age and analyse weight at 20 years of age in relation to weight and weight development during early childhood and adolescence. METHODS: A longitudinal, population-based study, which followed 496 children from birth to 20 years of age. Information about weight and height was collected from health records at child health centres and school health care. At 20 years of age, weight and height measurements were taken by one of the authors. RESULTS: At 20 years of age, 124 (25%) of the youth were obese or overweight. Of these youths, 60% had normal weight at 5.5 years. Of the teenagers who were overweight/obese at 15 years, 79% remained overweight/obese at 20 years of age. Out of the 124 overweight/obese at 20, 47% had normal weight at 15 years. [Corrections added after online publication on April 18, 2012: 'Out of the 124 obese at 20' has been changed to 'Out of the 124 overweight/obese at 20']. No relation was found between rapid weight gain during preschool age and overweight and obesity in 20 year-olds. CONCLUSIONS: The majority of those who were overweight/obese at 20 years of age were recruited after 5.5 years of age, and half of them in their late teens. Thus, during the preschool period, the entire population should be the target of primary prevention from overweight/obesity and, in the case of teenagers, prevention strategies should be developed for the whole population as well as treatment strategies for teenagers with established overweight/obesity. PMID- 22320838 TI - The growth of ionic crystals based on the halogenation of copper cluster anions. AB - We investigated the halogenation reactivity of copper cluster anions produced via a magnetron-sputter source after introduction into a fast-flow tube reaction apparatus simultaneously with chlorine gas. Interesting cluster products corresponding to [Cu(n)Cl(n+1)](-) (n = 1-6) were observed with notable stability, and the mass distribution of these clusters exhibits an exponential decay with increasing values of n. Reaction kinetics analysis is provided on the gas-phase reactivity of copper cluster anions with chlorine. First-principle calculations suggest a series of cubic-like structures for these species similar to the structure of alkali halide clusters due to their similar electronic configurations. These structures act as a starting point in the formation of ionic crystals. PMID- 22320839 TI - Are existing measures of overall diet quality associated with peak bone mass in young premenopausal women? AB - BACKGROUND: Low peak bone mass in young adulthood is associated with an increased risk of osteoporosis and fracture after menopause, and an understanding of the modifiable factors that contribute to low peak bone mass is important for fracture prevention. Diet is an important modifiable factor linked to bone health and, although studies have examined the role of individual dietary components in bone health, bone growth and maintenance are complex processes, and such studies may not adequately represent the role of diet in these processes. METHODS: To address this issue, a cross-sectional analysis of 226 healthy, premenopausal women aged 18-30 years was conducted to determine whether existing indices of overall diet quality are associated with bone density in premenopausal women nearing peak bone mass. Bone density was measured using dual-energy X-ray absorptiometry and diet quality was measured using two overall diet scores based on current dietary guidelines: the Recommended Food Score and the Alternate Healthy Eating Index (AHEI). RESULTS: In the multiple linear regression, bone density did not increase across quartiles of either diet quality score and was not associated with continuous diet quality variables. Furthermore, none of the individual AHEI components (e.g. fruit intake, vegetable intake) were associated with bone density. CONCLUSIONS: These findings suggest that existing diet quality scores are not appropriate for studies of peak bone mass, most likely because they do not give sufficient weight to foods and nutrients important to bone health. We recommend the development of a diet pattern index that better predicts bone mass measures. PMID- 22320840 TI - Development and criterion validity of a computerized text analysis measure of reflective functioning. AB - The Reflective Functioning scale (RF) is a narrative-based assessment of the capacity to coherently conceptualize one's own and others' subjective motivations, emotions, beliefs, and desires. We report the preliminary results of an effort to develop a computerized text analysis version (CRF) of the RF assessment system. A sample of 113 clinical and non-clinical Adult Attachment Interviews (AAI) were utilized to develop the CRF measure. Using the Marker Approach (Mergenthaler & Bucci, 1999), 54 linguistic markers of high RF language were identified. The associations between CRF and RF were significant in both a clinical sample of patients diagnosed with Borderline Personality Disorder (BPD) (Spearman rho=.57, p<.0001) and a non-clinical sample of adults (Spearman rho=.57, p=.002). These results suggest that a CRF rating scale is feasible, has preliminary criterion validity, and, therefore, has potential to facilitate the efficient assessment of RF. PMID- 22320841 TI - Risk prediction using a neonatal therapeutic intervention scoring system in VLBW and ELBW preterm infants. AB - BACKGROUND: The Neonatal Therapeutic Intervention Scoring System (NTISS) is a therapy-based severity-of-illness index, The aim of the present study was to evaluate whether: (i) NTISS can predict the severity of illness with the same accuracy both in very low-birthweight (VLBW) and extremely low-birthweight (ELBW) infants, using all parameters; and (ii) the performance of NTISS can be increased by using only the significant variables. METHODS: All inborns <1500 g, and all outborns <1500 g transferred in the first 12 h of postnatal life, were included. NTISS using 63 variables was assessed for all infants at the 24th hour. Predictive performance for the overall variables was assessed using area under the curve (AUC) for group 1 (500-1499 g), 2 (1000-1499 g) and 3 (500-999 g). Variables with good prediction were identified for each group and a second AUC was assessed using only sensitive variables. Receiver operating characteristic (ROC) curve area for all variables was compared with the ROC area for sensitive variables. RESULTS: A total of 364 preterm infants fulfilled the eligibility criteria. The AUC of groups 1, 2 and 3 with all variables were 0.851; 0.834 and 0.749, respectively. The number of parameters with good prediction was 33 in group 1, 30 in group 2 and 18 in group 3. The AUC for sensitive variables was 0.848 in group 1; 0.821 in group 2 and 0.823 in group 3. When compared, increase in the description of outcome was significant only for group 3 patients (P = 0.02). CONCLUSION: NTISS using all parameters seems to be less predictive in ELBW infants. It is probably related to the use of some interventions, done as a routine procedure in almost all ELBW preterm infants, therefore NTISS may be modified according to birthweight in order to obtain a more sensitive prediction. PMID- 22320843 TI - Carbon-ion radiation therapy for prostate cancer. AB - In 1994, carbon-ion radiotherapy was started at the National Institute of Radiological Sciences using the Heavy-Ion Medical Accelerator in Chiba. Between June 1995 and March 2000, two phase I/II dose escalation studies (protocols 9402 and 9703) of hypofractionated carbon-ion radiotherapy for both early- and advance stage prostate cancer patients had been carried out to establish radiotherapy technique and to determine the optimal radiation dose. To validate the feasibility and efficacy of hypofractionated carbon-ion radiotherapy, a phase II study (9904) was initiated in April 2000 using the shrinking field technique and the recommended dose fractionation (66 gray equivalents in 20 fractions over 5 weeks) obtained from the phase I/II studies, and was successfully completed in October 2003. The data from 175 patients in the phase II study showed the importance of an appropriate use of androgen deprivation therapy according to tumor risk group. Since November 2003, carbon-ion radiotherapy for prostate cancer was approved as "Highly Advanced Medical Technology" from the Ministry of Health, Labor, and Welfare, and since then approximately 1100 patients have received carbon-ion radiotherapy as of July 2011. In this review, we introduce our steps thorough three clinical trials carried out at National Institute of Radiological Sciences, and show the updated data of carbon-ion radiotherapy obtained from approximately 1000 prostate cancer patients. In addition, our recent challenge and future direction will be also described. PMID- 22320844 TI - Genetic variation in RTN4 3'-UTR and susceptibility to cervical squamous cell carcinoma. AB - Recent studies have suggested that RTN4 is a multifunctional gene, including inhibition of axonal regeneration, vascular remodeling, apoptosis, and tumor suppression. The TATC and CAA insertion/deletion polymorphisms of RTN4 3'-UTR have been linked to schizophrenia, depression, and dilated cardiomyopathy. To test whether these two polymorphisms are associated with cervical squamous cell carcinoma (CSCC), in this research, by using polymerase chain reaction polyacrylamide gel electrophoresis, we determined the genotypes of the TATC and CAA polymorphisms in 336 CSCC patients and 450 unrelated control subjects. Allele frequencies of TATC and CAA polymorphisms were not significantly different between CSCC patients and control subjects (odds ratio [OR]=1.22, 95% confidence interval [CI]=0.98-1.50 for TATC; OR=0.95, 95% CI=0.76-1.18 for CAA). Decreased CSCC risk was associated with TATC polymorphism in a recessive model (OR=0.49, 95% CI=0.30-0.77), while no significant association was observed between CAA polymorphism and CSCC in different genetic models. Results of stratified analysis revealed that both TATC and CAA polymorphisms were associated with high clinical stage, and CAA polymorphism was also associated with positive parametrial invasion (OR=0.69, 95% CI=0.48-0.98). The present study provides evidence that TATC and CAA insertion/deletion polymorphisms are associated with CSCC, indicating that genetic variation in RTN4 3'-UTR contributes to the susceptibility to CSCC. It is necessary to confirm these findings in ethnically different populations and with a larger sample. PMID- 22320845 TI - The relationship between antiglycation activity and procyanidin and phenolic content in commercial grape seed products. AB - Eight commercial grape seed products (GSPs) were assessed for their inhibition of the formation of advanced glycation end-products in vitro. All 8 commercial GSPs included in this study were potent inhibitors of advanced glycation end-product formation with IC(50) values ranging from 2.93 to 20.0 ug/mL. Total procyanidin content ranged from 60% to 73%. HPLC-DAD-ELSD results indicate that (+)-catechin, (-)-epicatechin, procyanidin B1, and procyanidin B2 were predominant and ubiquitously present in all the products under study, while gallic acid and procyanidin B4 were present in relatively minor amounts. The IC(50) values correlated with total phenolic content, and multiple regression analysis indicated that IC(50) is a linear function of the concentration of gallic acid and procyanidins B1, B2, and B4. Based on this study, GSPs have the potential to complement conventional diabetes medication toward disease management and prevention. PMID- 22320846 TI - A prospective randomized study to compare pelvic floor rehabilitation and dapoxetine for treatment of lifelong premature ejaculation. AB - Premature ejaculation (PE) is the most common male sexual disorder. We compared pelvic floor muscle rehabilitation to on-demand treatment with the selective serotonin reuptake inhibitor dapoxetine in 40 men with lifelong PE (baseline intra-vaginal ejaculatory latency time (IELT) <=1 min). Subjects were randomized into the following two treatment groups: (1) PFM rehabilitation or (2) 30 or 60 mg of on-demand dapoxetine. Total treatment time for both groups was 12 weeks, at the end of which, IELT mean values were calculated to compare the effectiveness of the two different therapeutic approaches. At the end of treatment, 11 of the 19 patients (57%) treated with rehabilitation were able to control the ejaculation reflex, with a mean IELT of 126.6 sec (range: 123.6-152.4 sec). In the dapoxetine group, after 12 weeks of therapy, 5 of 8 (62.5%) patients in the 30 mg subgroup and five of seven (72%) in the 60 mg subgroup had an IELT >180 sec (mean: 178.2 and 202.8 sec, respectively). The results obtained in the group treated with pelvic floor rehabilitation are promising, and this treatment represents an important cost reduction if compared to dapoxetine on-demand treatment. The present study confirms the data that are previously available in the literature on the efficacy and safety of the new inhibitor of serotonin reuptake, dapoxetine, as well as proposes and evaluates a new type of physical treatment that may be a viable therapeutic option for treatment of PE. PMID- 22320847 TI - Influence of finite-sites mutation, population subdivision and sampling schemes on patterns of nucleotide polymorphism for species with molecular hyperdiversity. AB - Molecular hyperdiversity has been documented in viruses, prokaryotes and eukaryotes. Such organisms undermine the assumptions of the infinite-sites mutational model, because multiple mutational events at a site comprise a non negligible portion of polymorphisms. Moreover, different sampling schemes of individuals from species with subdivided populations can profoundly influence resulting patterns and interpretations of molecular variation. Inspired by molecular hyperdiversity in the nematode Caenorhabditis sp. 5, which exhibits average pairwise differences among synonymous sites of >5% as well as modest population structure, we investigated via coalescent simulation the joint effects of a finite-sites mutation (FSM) process and population subdivision on the variant frequency spectrum. From many demes interconnected through a stepping stone migration model, we constructed local samples from a single deme, pooled samples from several demes and scattered samples of a single individual from numerous demes. Compared with a single panmictic population at equilibrium, we find that high population mutation rates induce a deficit of rare variants (positive Tajima's D) under a FSM model. Population structure also induces such a skew for local samples when migration is high and for pooled samples when migration is low. Contrasts of sampling schemes for C. sp. 5 imply high mutational input coupled with high migration. We propose that joint analysis of local, pooled and scattered samples for species with subdivided populations provides a means of improving inference of demographic history, by virtue of the partially distinct patterns of polymorphism that manifest when sequences are analyzed according to differing sampling schemes. PMID- 22320848 TI - Morphological distinction of cortisol-producing and aldosterone-producing adrenal cortical adenomas: not only possible but a critical clinical responsibility. PMID- 22320849 TI - Children's oral health-related knowledge, attitudes and beliefs as predictors of success in caries control during a 3.4-year randomized clinical trial. AB - OBJECTIVES: The aim of this study was to determine whether the baseline oral health-related knowledge, attitudes and beliefs of the participants in a randomized clinical trial (RCT) were associated with D(3)MFS increment. Additionally, the aim was to study whether the association was mediated by the two baseline behaviors, i.e. brushing teeth and eating candies. METHODS: Children in Pori, Finland (n = 493) aged 11-12 years, with active initial caries lesion(s) at baseline, were studied. The data were based on clinical examinations in 2001 and 2005 and on a questionnaire administered in 2001. Associations between success in caries control and baseline oral health-related knowledge, attitudes and the belief in keeping one's own teeth throughout life were evaluated using negative binomial regression analyses while considering the effects of the two baseline oral health behaviors. RESULTS: The degree of concern about getting decay in one's own teeth was associated with caries increment. The less concerned the child was about new caries lesions, the more likely he/she was to develop new cavities. This association was not mediated by the two behaviors. Those children who did not know whether or not their mother had cavities were more likely to fail in caries control than were children who knew about their mother's cavities. CONCLUSIONS: It is important to determine child's level of concern about getting cavities because children who are concerned about developing cavities are likely to succeed in caries control while the opposite is true for those children who do not share this concern. PMID- 22320850 TI - A novel pyrrolo[3, 2-d]pyrimidine derivative, as a vascular endothelial growth factor receptor and platelet-derived growth factor receptor tyrosine kinase inhibitor, shows potent antitumor activity by suppression of tumor angiogenesis. AB - We recently reported that compound 20d (comp.20d), a novel pyrrolo[3, 2 d]pyrimidine derivative, is a potent and selective inhibitor of tumor angiogenesis-related kinases, including vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR). In this study, we show that comp.20d potently blocks the VEGF- and PDGF-stimulated cellular phosphorylation (IC(50) = 2.5 and 3.6 nM, respectively) and proliferation of HUVECs and human coronary artery smooth muscle cells with IC(50) values of 2.8 and 9.6 nM, respectively, and potently inhibits the VEGF-induced tube formation of endothelial cells cocultured with fibroblasts (IC(50) = 3.3 nM). Given orally twice daily, comp.20d at the doses of 1.5-6 mg/kg showed antitumor effects in mice bearing various human cancer xenografts. Consistent with the anti-angiogenic mechanism of action, histological examination of tumors from comp. 20d-treated mice indicated a decrease in microvessel density and inhibition of pericyte recruitment to microvessels, and these were concomitant with decreased interstitial fluid pressure that allowed for therapeutic intratumoral uptake of CPT-11 (irinotecan hydrochloride). In conclusion, comp.20d is an extremely potent inhibitor of VEGFR/PDGFR kinases whose activities suggest therapeutic potential for the treatment of solid tumors that rely on angiogenesis for their survival. PMID- 22320851 TI - Postponing the morning dose of AEDs: effect on the epileptiform EEG activity. AB - BACKGROUND: The effects of postponing the morning dose of antiepileptic drugs (AEDs) before undergoing an electroencephalogram (EEG) on the likelihood of recording interictal epileptiform activity (IEA) in patients with epilepsy are unclear. METHODS: This was a prospective study on patients undergoing video-EEG monitoring. The 3-h recordings used for evaluation started at 08:00 am. Each subject received the usual AED dosage at 08:00 am on the first full day of recording but not until 11:00 am on the following day. IEA (spikes, sharp waves, and spike and wave complexes) was counted at 1-h intervals on each day and compared. Each subject served as his/her own control. The measureable serum drug levels were obtained at 10:00 am on both days. RESULTS: Fifty patients (age 32 +/ 11.7 years, 22 women) were enrolled. Forty-seven had focal epilepsy, and three had generalized epilepsy. Six were on monotherapy, and 44 were on polytherapy. The number of IEAs w/wo medication was similar throughout each hour. Twenty-five patients had IEA on the 1st day, and 28 had IEA on the 2nd day. Twenty-one had IEA on both days, while 18 had none on either day. Seven of the 25 without IEA on the 1st day had IEA on the 2nd day, and 4 of the 25 with IEA had no IEA on the 2nd day. Age, gender, epilepsy type, disease duration, seizure frequency, and AED type did not influence IEA. CONCLUSIONS: Delaying the morning dose of AEDs prior to an EEG tracing was not associated with increased IEA in patients with epilepsy. PMID- 22320852 TI - Active thermal tracer tests for improved hydrostratigraphic characterization. AB - Subsurface heterogeneity in hydraulic properties and processes is a fundamental challenge in hydrogeology. We have developed an improved method of borehole dilution testing for hydrostratigraphic characterization, in which distributed temperature sensing (DTS) is used to monitor advective heat movement. DTS offers many advantages over conventional technologies including response times in the order of seconds rather than minutes, the ability to profile temperature synoptically in a well without disturbing the fluid column, sensitivity to a wider range of flow rates than conventional spinner and heat pulse flow meters, and the ease of interpretation. Open-well thermal dilution tests in two multiaquifer wells near Madison, Wisconsin, provided detailed information on the borehole flow regimes, including flow rates and the locations of inflows from both fractures and porous media. The results led to an enhanced understanding of flow in a hydrostratigraphic unit previously conceptualized as homogenous and isotropic. PMID- 22320853 TI - A new PICTure of nucleolar stress. AB - Cell growth demands new protein synthesis, which requires nucleolar ribosomal functions. Ribosome biogenesis consumes a large proportion of the cell's resources and energy, and so is tightly regulated through an intricate signaling network to guarantee fidelity. Thus, events that impair ribosome biogenesis cause nucleolar stress. In response to this stress, several nucleolar ribosomal proteins (RPs) translocate to the nucleoplasm and bind to MDM2. MDM2-mediated ubiquitination and degradation of the tumor suppressor p53 is then blocked, resulting in p53 accumulation and the induction of p53-dependent cell cycle arrest and apoptosis. Nucleolar stress is therefore a quality control surveillance mechanism that monitors the synthesis and assembly of the rRNA and protein components of ribosomes. Although nucleolar stress signaling pathways have been extensively analyzed, critical questions remain about their regulatory mechanisms. For example, how do RPs translocate from the nucleolus to the nucleoplasm to exert their functions, and do these p53-regulating RPs influence the prognosis of human cancer patients? Our laboratory recently identified the nucleolar protein PICT1 as a novel regulator of nucleolar stress. PICT1 sequesters the ribosomal protein RPL11 in the nucleolus, preventing it from binding to MDM2. MDM2 is then free to degrade p53, favoring tumor cell growth. Accordingly, the level of PICT1 in a tumor is becoming a useful prognostic marker for human cancers. This review summarizes the evidence that links nucleolar stress to tumorigenesis, and casts PICT1 as an oncogenic player in human cancer biology. PMID- 22320854 TI - Cardiovascular disease risk assessment and prevention in blood donors. AB - BACKGROUND: Blood centers have implemented public health initiatives, including cardiovascular disease (CVD) screening, to improve donor and community health and serve as an incentive to donate. STUDY DESIGN AND METHODS: CVD risk screening and counseling were performed at mobile blood drives in diverse neighborhoods. Risk factors were determined by point-of-care testing (total cholesterol, high-density lipoprotein, and hemoglobin A1c levels), interviews, and physical examinations (body mass index, waist circumference, and blood pressure). Results were confidentially relayed to participant by health counselors. A 60-day follow-up survey was sent to some participants. RESULTS: Over 11 months, 2406 participants (44% male; mean age 28 +/- 16; 67% minority racial/ethnic group) were screened at 290 mobile drives. A total of 92% of participants had medical insurance. A total of 14% had none, 26% one, 33% two, and 27% three or more risk factors. A total of 72% of teenage participants had at least one risk factor. A total of 18% of participants who were taking medications for risks were poorly controlled. A total of 15% had newly identified risks. A total of 711 participants completed follow-up survey: 21% sought medical care, 51% were motivated to change their lifestyle, 81% were pleased with screening, 48% were more likely to donate, and 62% recommended donation to friends and family because of the screening. CONCLUSION: CVD risk screening and counseling can occur during a mobile blood drive. A majority of participants screened had risk factors. Follow-up surveys showed that the program was well received. Further studies are planned to evaluate long-term effects of the program on donor health and donor return rates. PMID- 22320855 TI - Current practice of pulse oxygen saturation targets and limits in neonatal intensive care units in Australia and New Zealand. PMID- 22320856 TI - Urban landscape genetics: canopy cover predicts gene flow between white-footed mouse (Peromyscus leucopus) populations in New York City. AB - In this study, I examine the influence of urban canopy cover on gene flow between 15 white-footed mouse (Peromyscus leucopus) populations in New York City parklands. Parks in the urban core are often highly fragmented, leading to rapid genetic differentiation of relatively nonvagile species. However, a diverse array of 'green' spaces may provide dispersal corridors through 'grey' urban infrastructure. I identify urban landscape features that promote genetic connectivity in an urban environment and compare the success of two different landscape connectivity approaches at explaining gene flow. Gene flow was associated with 'effective distances' between populations that were calculated based on per cent tree canopy cover using two different approaches: (i) isolation by effective distance (IED) that calculates the single best pathway to minimize passage through high-resistance (i.e. low canopy cover) areas, and (ii) isolation by resistance (IBR), an implementation of circuit theory that identifies all low resistance paths through the landscape. IBR, but not IED, models were significantly associated with three measures of gene flow (Nm from F(ST) , BayesAss+ and Migrate-n) after factoring out the influence of isolation by distance using partial Mantel tests. Predicted corridors for gene flow between city parks were largely narrow, linear parklands or vegetated spaces that are not managed for wildlife, such as cemeteries and roadway medians. These results have implications for understanding the impacts of urbanization trends on native wildlife, as well as for urban reforestation efforts that aim to improve urban ecosystem processes. PMID- 22320857 TI - Surface phosphatase in Rhinocladiella aquaspersa: biochemical properties and its involvement with adhesion. AB - Rhinocladiella aquaspersa is an etiologic agent of chromoblastomycosis, a subcutaneous chronic infectious disease. In the present work, we found that the three morphological forms of this fungus (conidia, mycelia and sclerotic bodies) expressed different levels of ecto-phosphatase activity. Our results demonstrated that surface conidial enzyme is an acid phosphatase, inhibited by sodium salts of molybdate, orthovanadate and fluoride and that the inhibition caused by orthovanadate and molybdate was irreversible. The conidial ecto-phosphatase efficiently released phosphate groups from different phosphorylated substrates, causing a higher rate of phosphate removal when p-nitrophenylphosphate was used as substrate. This ecto-enzyme of R. aquaspersa is modulated by Co(2 +) ions and inorganic phosphate (Pi). Accordingly, removal of Pi from the culture medium resulted in a marked (121-fold) increase of ecto-phosphatase activity. Surface phosphatase activity is apparently involved in fungal adhesive properties, since the attachment of R. aquaspersa to epithelial cells was reversed by the pre treatment of the conidia with orthovanadate, molybdate and anti-phosphatase antibody. Corroborating this finding, conidia with greater ecto-phosphatase activity (grown in Pi-depleted medium) showed higher adherence to epithelial cells than fungi cultivated in the presence of Pi. PMID- 22320858 TI - Suppression of mesoscopic order by complementary interactions in supramolecular polymers. AB - We show here that complementary interactions can suppress mesoscopic order and thus lead to a counterintuitive change in material properties. We present results for telechelic supramolecular polymers based on poly(propylene oxide) (PPO), thymine (Thy), and diaminotriazine (DAT). The self-complementary systems based on Thy exhibit lamellar order and 2D crystallization of Thy in the bulk. We show that the microphase segregation is inhibited by addition of DAT: the strong complementary Thy-DAT interaction inhibits crystallization of thymine in microdomains and lamellar structuration. As a result, the supramolecular polymer with only weakly self-complementary stickers is a solid, whereas the supramolecular polymer with strongly complementary stickers is a liquid. PMID- 22320859 TI - Calculation of exchange coupling constants in triply-bridged dinuclear Cu(II) compounds based on spin-flip constricted variational density functional theory. AB - The performance of the second-order spin-flip constricted variational density functional theory (SF-CV(2)-DFT) for the calculation of the exchange coupling constant (J) is assessed by application to a series of triply bridged Cu(II) dinuclear complexes. A comparison of the J values based on SF-CV(2)-DFT with those obtained by the broken symmetry (BS) DFT method and experiment is provided. It is demonstrated that our methodology constitutes a viable alternative to the BS-DFT method. The strong dependence of the calculated exchange coupling constants on the applied functionals is demonstrated. Both SF-CV(2)-DFT and BS DFT affords the best agreement with experiment for hybrid functionals. PMID- 22320860 TI - Influence of atorvastatin and carboxymethylated glucan on the serum lipoprotein profile and MMP activity of mice with lipemia induced by poloxamer 407. AB - The effects of atorvastatin and carboxymethylated beta-glucan (CMG) on the lipoprotein-cholesterol (LP-C) and lipoprotein-triglyceride (LP-TG) fractions and subfractions at the early stage of murine hyperlipidemia, and its pleiotropic anti-inflammatory effects, were studied. Atorvastatin and CMG were administered in ICR male mice with acute lipemia induced with a single injection of poloxamer 407 (P-407). A novel small-angle X-ray scattering method for the determination of fractional and subfractional composition of LP-C and LP-TG was used. In P-407 treated animals, there was a drastic increase of total cholesterol and especially TG. Atorvastatin decreased both the total cholesterol and TG, but not to control levels. CMG primarily decreased TG and was not as potent as atorvastatin. P-407 increased atherogenic LDL-C (IDL-C and LDL(1-3)-C subfractions) and very low density lipoprotein-C (VLDL-C) (VLDL(1-2)-C and VLDL(3-5)-C subfractions) fractions, with an increase of the total anti-atherogenic HDL-C fraction (HDL(2) C subfraction). Atorvastatin treatment of lipemia was followed by a decrease in the total LP-C, total LDL-C (LDL(1-3)-C subfraction), and the LDL(1-3)-TG subfraction. Additionally, atorvastatin treatment resulted in an increase in the serum matrix metalloproteases activity both in control and P-407-treated mice. In general, high-dose atorvastatin therapy exerts its lipid-lowering and pleiotropic effects in the early stages of acute lipemia induced in mice by treatment with P 407. PMID- 22320861 TI - Cup introduction, drink type and vitamin supplementation in preterm babies at 11 25 months. AB - BACKGROUND: To avoid adverse effects of prolonged bottle use, the recommendations are that full-term babies are introduced to cups from 6 months and discouraged bottles from 12 months old. There are no recommendations for preterm babies. In the UK, the Department of Heath recommends the introduction of vitamin supplements, alongside the transition from formula to cow's milk. The present study aimed to determine age of cup introduction in a group of preterm babies, identify drinks offered from bottles versus cups and the types of cups used, and establish the prevalence and appropriateness of vitamin supplementation. METHODS: A validated postal questionnaire was sent to the parents of 369 babies born <34 weeks of gestation at Queen Charlottes Neonatal Unit; 104 sent in 2003 and 265 sent in 2004-2005. The questionnaire was sent when the babies were calculated to be between 12 and 18 months (all ages stated are uncorrected). A separate questionnaire was sent for each baby from multiple pregnancies. RESULTS: The questionnaire return rate was 46% (n = 169). Length of gestation (P < 0.001), hospital stay (P = 0.009), birth weight (P = 0.002) and maternal age (P < 0.001) were significantly greater and more mothers were of European origin (P = 0.036) for those babies for whom questionnaires were returned compared to nonresponders. Infant gender did not differ. Fifty-seven percent had been introduced to a cup before 12 months, distribution was: 58% (n = 53) of singletons, 54% (n = 37) of twins and 67% (n = 6) of triplets. This rose to 80% before 13 months. Thirteen percent (n = 22) had not started drinking from a cup and 17% (n = 29) only used cups at the time of the questionnaire. Cow's milk had been introduced to 69% (n = 117) of all babies and 32% (n = 54) were still on formula (10 on both and eight were on neither; hence, the figures do not sum to 100%). Cow's milk was drunk from bottles by 56% (n = 95) and formula by 31% (n = 52). A significantly greater proportion of twins and triplets were drinking cow's milk compared to singletons [80% (n = 62) versus 60% (n = 55) P = 0.005] and significantly fewer were drinking formula [22% (n = 17) versus 40% (n = 37) P = 0.012]. Water was the drink most commonly given from a cup (80%) (n = 135) followed by juice, which was given to 64% (n = 108). Juice drinks were given by bottle in 16% (n = 27). Fifty-two percent (n = 88) used a 'spill-proof' cup some of the time. Vitamins were given as recommended in 18% (n = 31), given even though not recommended in 12% (n = 20), not given but recommended in 49% (n = 83) and appropriately not given in 21% (n = 35). A greater percentage of twins and triplets, compared to singletons, were not commenced on vitamins, even though they were no longer drinking formula. CONCLUSIONS: The present study reports baseline data on cup introduction in preterm babies both from singleton and multiple births. The data suggest that education about appropriate bottle drinks, timing of cup introduction, suitable cups and the correct use of vitamin drops is required. However, because the profile of responders differed from nonresponders, these results may not be applicable to all preterm babies. PMID- 22320862 TI - Grape juice concentrate modulates p16 expression in high fat diet-induced liver steatosis in Wistar rats. AB - PURPOSE: The goal of this study was to investigate whether subchronic treatment with grape juice concentrate is able to protect the liver from high fat diet injury in rats. The effects of grape juice concentrate treatment on histopathological changes, and immunohistochemistry for p53, p16 and p21 were evaluated. METHODS: Male Wistar rats (n = 18) were distributed into three groups: group 1: negative control; group 2: cholesterol at 1% (w/w) in their diet, treated during 5 weeks; and group 3: cholesterol at 1% in their chow during 5 weeks, and grape juice concentrate at 222 mg per day in their drinking-water in the last week only. RESULTS: The results pointed out that treatment with grape juice concentrate did not show remarkable differences regarding liver tissue in the cholesterol-exposed group when compared to group 2. However, grape juice concentrate was able to modulate p16 immunoexpression when compared to high fat diet group. p53 and p21 did not show any significant statistical differences among groups. CONCLUSION: Taken together, our results suggest that subchronic grape juice concentrate administration was able to modulate cell cycle control by downregulation of p16 immunoexpression in high fat diet-induced liver steatosis in rats. PMID- 22320863 TI - HIF-1alpha acts downstream of TNF-alpha to inhibit vasodilator-stimulated phosphoprotein expression and modulates the adhesion and proliferation of breast cancer cells. AB - Metastasis is the leading cause of death in breast cancer patients. Recent evidence suggests that inflammation-related cytokine tumor necrosis factor-alpha (TNF-alpha) is implicated in tumor invasion and metastasis, but the mechanism of its involvement remains elusive. In this study, we employed MCF-7 breast cancer cells as an experimental model to demonstrate that TNF-alpha inhibits breast cancer cell adhesion and cell proliferation through hypoxia inducible factor 1alpha (HIF-1alpha) mediated suppression of vasodilator-stimulated phosphoprotein (VASP). We observed that TNF-alpha treatment attenuated the adhesion and proliferation of MCF-7 cells it also dramatically increased HIF-1alpha expression and decreased VASP expression. Through a variety of approaches, including promoter assay, electrophoretic mobility shift assay (EMSA), and chromatin immunoprecipitation (ChIP), we identified VASP as a direct target gene of HIF 1alpha. In addition, we confirmed that HIF-1alpha mediated the repression of VASP expression by TNF-alpha in MCF-7 cells. We also demonstrated that exogenous VASP expression or knockdown of HIF-1alpha relieved TNF-alpha induced inhibition of cell adhesion and proliferation. We identified a novel TNF-alpha/HIF-1alpha/VASP axis in which HIF-1alpha acts downstream of TNF-alpha to inhibit VASP expression and modulate the adhesion and proliferation of breast cancer cells. These data provide new insight into the potential anti-tumor effects of TNF-alpha. PMID- 22320864 TI - Promoter variant-dependent mRNA expression of the MEF2A in longissimus dorsi muscle in cattle. AB - The myocyte enhancer factor 2A (MEF2A) gene encodes a member of the myocyte enhancer factor 2 (MEF2) protein family that is involved in vertebrate skeletal, cardiac, and smooth muscle development and differentiation during myogenesis. According to recent studies, MEF2 genes might be major regulators of postnatal skeletal muscle growth; thus, they are considered to be important, novel candidates for muscle development and body growth in farm animals. The aim of the present study was to search for polymorphisms in the bovine MEF2A gene and analyze their effect on the MEF2A mRNA expression level in the longissimus dorsi muscle of Polish Holstein-Fresian cattle. In total, 4094 bp of the whole coding sequence and the promoter region of MEF2A were re-sequenced in 30 animals, resulting in the detection of 6 novel variants as well as one previously reported SNP. Three linked mutations in the promoter region (-780T/G, g.-768T/G, and g. 222A/G) and only two genotypes were identified in two Polish breeds (TTA/TTA and TTA/GGG). Three SNPs in the coding region [g.1599G/A (421aa), g.1626G/A (429aa), and g.1641G/A (434aa)] appeared to be silent substitutions and segregated as two intragene haplotypes: GGG and AAA. Expression analysis showed that the mutations in the promoter region are highly associated with the MEF2A mRNA level in the longissimus dorsi muscle of bulls carrying two different genotypes. The higher MEF2A mRNA level was estimated in the muscle of bulls carrying the TTA/TTA (p<0.01) genotype as compared with those with TTA/GGG. The results obtained suggest that the nucleotide sequence mutation in MEF2A might be useful marker for body growth traits in cattle. PMID- 22320866 TI - Quantitative assessment of the influence of paraoxonase 1 activity and coronary heart disease risk. AB - Human paraoxonase 1 (PON1) is a calcium-dependent high-density lipoprotein associated ester hydrolase that has attracted considerable attention as a candidate factor for coronary heart disease (CHD) based on its function as a key factor in lipoprotein catabolism pathways. This meta-analysis aimed to clarify the inconsistency of published studies and to establish a comprehensive picture of the relationship between PON1 activity and CHD susceptibility. A systematic search was performed from PubMed, Web of Science, EMBASE, and CNKI databases. Ratio of means (RoM) between case and control and 95% confidence intervals (CIs) were calculated using a random-effects model. The source of heterogeneity was explored by subgroup analysis and meta-regression. We identified 47 eligible studies including a total of 9853 CHD cases and 11,408 controls. The pooled analysis showed that CHD patients had a 19% lower PON1 activity than did the controls (RoM=0.81; 95% CI: 0.74-0.89, p<10(-5)). In the subgroup analyses by CHD end points, a similar effect size was observed with coronary stenosis and myocardial infarction subgroups, with corresponding RoM of 0.81 (95% CI: 0.73 0.89, p<10(-4)) and 0.83 (95% CI: 0.74-0.93, p=0.001), respectively. Decreased PON1 activity associated with CHD risk was observed in almost all subgroup analysis according to ethnicity, sample size, study design, mean age of cases, source, and type of control. Decreased PON1 activity may act as a risk factor for the development of CHD. Progressive decrease in serum PON1 activity may exist for an individual with severe disease. However, larger studies using a prospective approach are needed to confirm our results. PMID- 22320865 TI - Inhibition of mammalian target of rapamycin signaling by CCI-779 (temsirolimus) induces growth inhibition and cell cycle arrest in Cashmere goat fetal fibroblasts (Capra hircus). AB - The mammalian target of rapamycin (mTOR) is a Ser/Thr kinase. It plays an evolutionarily conserved role in regulating cell growth, proliferation, survival, and metabolism via different cellular processes. The purpose of this study was to explore the inhibitory effects of CCI-779 (temsirolimus), a specific mTOR inhibitor, on mTOR signaling, and examine the mechanism of cell growth suppression by CCI-779 in Cashmere goat fetal fibroblasts (GFb cells). GFb cells were sensitive to CCI-779 and the survival rate of cells treated with >3.0 MUM of CCI-779 was significantly reduced compared with the control (p<0.01). CCI-779 inhibited the phosphorylation of mTOR (at Ser2448) and S6 (at Ser240/244), and the expression of mTOR, p70S6K, and S6. Thus, CCI-779 was toxic to GFb cells, and it induced a dose-dependent decrease in cell proliferation and caused G1/S cell cycle arrest. Taken together, these data show that CCI-779 can inhibit mTOR signaling and proliferation in GFb cells in vitro. Therefore, mTOR is an important regulator for GFb cell growth and proliferation. PMID- 22320867 TI - Prognostic significance of phosphorylated STAT-1 expression in premenopausal and postmenopausal patients with invasive breast cancer. AB - AIMS: STAT-1 is the first member of the family of signal transducers and activators of transcription (STATs). In breast cancer experimental models, an apoptotic and antiproliferative effect has been demonstrated. Our aim was to study the role of phosphorylated STAT-1 (pSTAT-1) in invasive breast carcinoma and its prognostic significance in premenopausal and postmenopausal patients. METHODS AND RESULTS: Immunohistochemistry was performed in 165 patients in order to detect the expression of pSTAT-1 and its correlation with oestrogen receptor (ER), progesterone receptor (PR), caspase-3, and pAkt. pSTAT-1 was immunodetected in the cytoplasm of the malignant cells (11.6%). In premenopausal patients, cytoplasmic pSTAT-1 was positively correlated with stage (P = 0.014), ER (P = 0.008), caspase-3 (P = 0.029), and pAkt (P = 0.045). Univariate analysis showed that cytoplasmic pSTAT-1 was associated with poor overall survival (P = 0.042) and the phenotype of pSTAT-1/ER or PR coexpression with shorter disease free survival (P = 0.012). In contrast, in postmenopausal patients, no association with clinicopathological parameters and survival was observed, except for the relationship of pSTAT-1/ER or PR coexpression with longer disease-free survival (P = 0.034). CONCLUSIONS: This is the first study examining the role of pSTAT-1 in premenopausal and postmenopausal women with invasive breast cancer. Our results suggest that pSTAT-1 is related to tumour progression in premenopausal patients through the advanced stage and worse survival. PMID- 22320868 TI - Clinical and social characteristics of Korean men with Klinefelter syndrome. AB - OBJECTIVES: To investigate the characteristics of Klinefelter syndrome in a consecutive series of men consulting for sexual as well as fertility problems in Korea. METHODS: A total of 179 men with non-mosaic 47,XXY Klinefelter syndrome of the 1876 azoospermic males who visited the fertility center of our university hospital between January 2002 and January 2010 were included in this analysis. Their semen characteristics, hormone profiles, size of the prostate gland, and education level were assessed and compared with an age-matched control group of 218 fertile males. Additionally, a histological evaluation was carried out. RESULTS: Prostate size, testicular volume, semen volume and symptom severity showed statistically significant differences in both groups (P < 0.0001). As the severity of signs and symptoms worsened, the education level decreased. Each degree of signs and symptoms was associated with a different level of education, as well as with significant differences in the level of testosterone and testicular volume (P < 0.05). Spearman's correlation coefficient showed the severity of signs and symptoms was associated with testosterone (P < 0.0001). CONCLUSIONS: Testosterone has the strongest negative association with the severity of signs and symptoms in patients with Klinefelter syndrome. It influences the reproductive capacity, as well as the manifested signs and symptoms of hypogonadism. Furthermore, it is also associated with various aspects of life in these patients. PMID- 22320869 TI - Gonadal and extragonadal germ cell tumours in the United States, 1973-2007. AB - Germ cell tumours (GCTs) most often arise in the gonads, but some develop extragonadally. The aim of this study was to examine gender- and race-specific trends in incidence and survival of gonadal (GGCTs) and extragonadal GCTs (EGCTs) in the US from 1973 to 2007. We also examined the topographical distribution of EGCTs by race and gender. We estimated age-specific and age-standardized incidence rates and 5-year relative survival rates (RSR) of GCTs using the Surveillance, Epidemiology and End Results (SEER) Program (SEER nine registries). GCTs and their topographical sites were identified using ICD-O morphology and topography codes. Of 21,170 GCTs among males, 5.7% were extragonadal (Whites 5.5%; Blacks 16.3%). Of 2093 GCTs among females, 39.3% were extragonadal (Whites, 36.9%; Blacks 51.0%). The incidence of GGCT was much higher among White (56.3/1,000,000) than Black males (10.0/1,000,000), while there was no difference in incidence between White and Black females (3.2/1,000,000). The rates of EGCT among men and women of both races were similar (range:1.9-3.4/1,000,000). The most frequent extragonadal sites were mediastinum among males and placenta among females. The 5-year RSR of testicular GCT was higher among Whites (97%) than Blacks (90%), as was the 5-year RSR of ovarian GCT (Whites, 92%; Blacks 85%). In general, the 5-year RSRs of EGCTs were lower than the 5-year RSRs of GGCTs. The different incidence trends of GGCTs and EGCTs and distinct age-specific incidence patterns by anatomical site of EGCTs suggest that GGCTs and EGCTs may have different aetiologies. PMID- 22320870 TI - Maternal childrearing anxiety reflects childrearing burden and quality of life. AB - BACKGROUND: The government of Japan has recently initiated public programs to allay maternal childrearing anxiety. The aim of the present study was to determine the prevalence of childrearing anxiety and describe its relationships with perceived childrearing burden and maternal quality of life (QOL). METHODS: A secondary analysis was done of survey data from 1229 mothers enrolled in the Seiiku Birth Cohort Study at the National Center for Child Health and Development between November 2003 and December 2006. Childrearing anxiety was determined by asking mothers, at infant age 3 months, 'Regarding childrearing, do you have any anxiety or worry?'. Childrearing burden was assessed in specific categories such as physical fatigue, household expenses, and personal time. The validated Japanese translation of the WHOQOL-BREF instrument was used to measure Maternal QOL. RESULTS: Sixty-four percent of mothers reported some and 9% much childrearing anxiety. In total, 73% percent of mothers reported any childrearing anxiety. As childrearing anxiety increased from 'none' to 'some' and 'much', the proportion of mothers who reported any childrearing burden increased from 75% to 99% (P < 0.001). QOL scores in each of four domains (physical, psychological, social relationships, and environment) decreased with increasing level of anxiety (P < 0.001). Primiparity, pregnant with more than a singleton and admission to the neonatal intensive care unit were associated with greater anxiety. CONCLUSIONS: The strong associations between childrearing anxiety and childrearing burden, and between childrearing anxiety and maternal QOL, suggest that childrearing anxiety is an empirically credible and measurable phenomenon. PMID- 22320871 TI - A new compression suture to prevent 'uterine sandwich' from sliding off. PMID- 22320872 TI - From new nurse practitioner to primary care provider: bridging the transition through FQHC-based residency training. AB - Community Health Center, Inc. (CHCI), a multi-site, federally qualified, health center (FQHC) in Connecticut, implemented a one-year-residency program for new nurse practitioners (NPs) in 2007. This residency program is specifically designed for family nurse practitioners intending to practice as primary care providers in federally qualified health centers. These centers comprise the nation's largest safety net setting; they are commonly referred to as community health centers. Supported in part by the Health Resources Service Administration, health centers are private nonprofit or public organizations serving populations with limited access to healthcare. They are located in designated, high need communities; governed by patient-majority boards of directors; and provide comprehensive, primary healthcare services. The author begins by reviewing the background and context for a nurse practitioner residency program, the importance of NP residency programs, and the recruitment and selection of NP residents. She explains how the residents are trained to a model of care and the content of care. She furthers the discussion by addressing program evaluation and outcomes and costs. Implications for national health policy, clinical practice, and nursing and areas for further research are presented. This article is timely in light of recent recommendations in the Institute of Medicine's 2010 report on the future of nursing recommending the development of residency programs for new, advanced practice registered nurses. PMID- 22320873 TI - Open access part II: the structure, resources, and implications for nurses. AB - Electronic publishing has changed the landscape for broadcasting scholarly information. Now Open Access is globalizing scholarly work. Open Access facilitates lifelong learning habits; enhances dissemination and distribution of information; impacts the informatics curriculum; supports active learning; and provides areas for nursing informatics research. In the last 10 years the Open Access Movement has formalized into a distinct publishing paradigm. Many free, full-text resources are now available to guide nursing practice. This article describes the Open Access structure, and provides suggestions for using Open Access resources in classroom and practice settings. The nursing community is only beginning to accept and use Open Access. Yet all nurses should be aware of the unique opportunity to obtain free, current, and scholarly information through a variety of avenues and also to incorporate this information into their daily practice. The resources presented in this article can be used to increase nursing knowledge and support evidence-based practice. PMID- 22320874 TI - Open access part I: the movement, the issues, and the benefits. AB - The advent of Open Access (OA) has changed the landscape of accessing digital information globally. OA offers valuable free, full-text, online resources for all health-related professionals, regardless of the practice setting. Because much scholarly information may now be accessed without charge, nurses worldwide can reach a higher level of information competency-a prime requirement for evidence-based practice. This article provides a brief account of the OA movement, introduces new terminology, discusses various publishing models, and elucidates issues surrounding the choice to publish in OA journals. Many stakeholders derive benefits from Open Access. Nursing must take action to participate in and promote the OA movement in order to derive the maximum gain for our science. PMID- 22320875 TI - Promoting safe use of medical devices. AB - Although patient safety initiatives in the clinical environment have focused primarily on medication errors to date, medical devices also contribute significantly to patient injuries and deaths. This article addresses the Food and Drug Administration's (FDA) efforts to promote safe use of medical devices by nurses at the point of care. The nurses with whom we have discussed the effects of medical devices, and also those surveyed by the medical device industry and professional nursing associations, are concerned about the profound effects, both desired and undesired, that medical devices have on patient outcomes. We believe that professional nurses, individually and through their professional associations, can help address these concerns by becoming aware of how to share their observations with the FDA and by working with their professional associations to develop position statements that focus on achieving safe and desired patient outcomes. In this article we will identify factors contributing to adverse events related to medical devices, address the need for more medical device adverse-event reporting, describe position statements that have already been made by some professional associations, and share insights regarding future directions along with ideas for educating staff to use medical devices safely. PMID- 22320876 TI - Ethics: ethics and pain management in hospitalized patients. PMID- 22320877 TI - The voice of Florence Nightingale on advocacy. AB - Modern nursing is complex, ever changing, and multi focused. Since the time of Florence Nightingale, however, the goal of nursing has remained unchanged, namely to provide a safe and caring environment that promotes patient health and well being. Effective use of an interpersonal tool, such as advocacy, enhances the care-giving environment. Nightingale used advocacy early and often in the development of modern nursing. By reading her many letters and publications that have survived, it is possible to identify her professional goals and techniques. Specifically, Nightingale valued egalitarian human rights and developed leadership principles and practices that provide useful advocacy techniques for nurses practicing in the 21st century. In this article we will review the accomplishments of Florence Nightingale, discuss advocacy in nursing and show how Nightingale used advocacy through promoting both egalitarian human rights and leadership activities. We will conclude by exploring how Nightingale's advocacy is as relevant for the 21st century as it was for the 19th century. PMID- 22320878 TI - Patient advocacy in the community and legislative arena. AB - Nurses have hundreds of patient experiences upon which to draw in order to impact public policy. It is our obligation to strengthen skills that enable us to influence public policy so we can better serve patients. This article provides examples of how nurses can translate their hands-on experience with patients into steps that will influence policy. We begin by describing advocacy and providing examples of how nurses can advocate in the community, specifically in economic matters and the educational and healthcare systems. Then we describe the process for advocating in the legislative arena. We conclude by noting that the public needs the voice of nursing in public policy and that now is the time to move forward to advocate for patients in these various arenas. PMID- 22320879 TI - Role of professional organizations in advocating for the nursing profession. AB - Professional organizations and associations in nursing are critical for generating the energy, flow of ideas, and proactive work needed to maintain a healthy profession that advocates for the needs of its clients and nurses, and the trust of society. In this article the author discusses the characteristics of a profession, reviews the history of professional nursing organizations, and describes the advocacy activities of professional nursing organizations. Throughout, she explains how the three foundational documents of the nursing profession emphasize nursing advocacy by the professional organizations as outlined in the American Nurses Association Code of Ethics for Nurses With Interpretive Statements. The author concludes by encouraging all nurses to engage in their professional organizations and associations, noting how these organizations contribute to the accountability and voice of the profession to society. PMID- 22320880 TI - Advocating for nurses and nursing. AB - Every nurse has the opportunity to make a positive impact on the profession through day-to-day advocacy for nurses and the nursing profession. In this article the author defines advocacy; describes advocacy skills every nurse can employ to advocate for a safe and healthy work environment; and explains how nurses can advocate for nursing as part of their daily activity whether they are point-of-care nurses, nurse managers, or nurse educators. The advocacy practices discussed are applicable whether advocating on one's own behalf, for colleagues at the unit level, or for issues at the organizational or system level. PMID- 22320881 TI - Advocating globally to shape policy and strengthen nursing's influence. AB - The International Council of Nurses is a federation of national nursing associations that works to enable nurses to speak with one voice so as to influence health policy and advance the profession of nursing. In this article the author highlights how nurses can advocate for the nursing profession by coordinating nursing actions to develop both public and healthcare-service policies. He addresses issues that are common in many parts of the world and provides examples drawn from real-life experiences that illustrate how nurses in El Salvador, Rwanda, Paraguay, Papua New Guinea, and Iran have worked in their countries to coordinate their actions and advocate for public and/or healthcare service policies within their countries. He concludes by noting that all nurses must do their part and use a wide range of opportunities creatively, and with clarity of intent, to improve the profession and the lives of the millions of people who depend upon us. PMID- 22320882 TI - Informatics: where is it? PMID- 22320883 TI - Field study of subsurface heterogeneity with steady-state hydraulic tomography. AB - Remediation of subsurface contamination requires an understanding of the contaminant (history, source location, plume extent and concentration, etc.), and, knowledge of the spatial distribution of hydraulic conductivity (K) that governs groundwater flow and solute transport. Many methods exist for characterizing K heterogeneity, but most if not all methods require the collection of a large number of small-scale data and its interpolation. In this study, we conduct a hydraulic tomography survey at a highly heterogeneous glaciofluvial deposit at the North Campus Research Site (NCRS) located at the University of Waterloo, Waterloo, Ontario, Canada to sequentially interpret four pumping tests using the steady-state form of the Sequential Successive Linear Estimator (SSLE) (Yeh and Liu 2000). The resulting three-dimensional (3D) K distribution (or K-tomogram) is compared against: (1) K distributions obtained through the inverse modeling of individual pumping tests using SSLE, and (2) effective hydraulic conductivity (K(eff) ) estimates obtained by automatically calibrating a groundwater flow model while treating the medium to be homogeneous. Such a K(eff) is often used for designing remediation operations, and thus is used as the basis for comparison with the K-tomogram. Our results clearly show that hydraulic tomography is superior to the inversions of single pumping tests or K(eff) estimates. This is particularly significant for contaminated sites where an accurate representation of the flow field is critical for simulating contaminant transport and injection of chemical and biological agents used for active remediation of contaminant source zones and plumes. PMID- 22320884 TI - MARVELD1 inhibited cell proliferation and enhance chemosensitivity via increasing expression of p53 and p16 in hepatocellular carcinoma. AB - We have previously found that expression of MARVELD1 was remarkably downregulated in multiple tumor tissues, but unclear in hepatocellular carcinoma (HCC) and its function has not been explored yet. In the present study, to uncover the underlying mechanism of MARVELD1 in the pathogenesis and development of HCC, we investigated the expression pattern of MARVELD1 and its effect on tumor proliferation in HCC. The results indicated the frequent downregulation of MARVELD1 in clinic samples and cell lines of HCC resulted from promoter methylation, as well as genetic deletion. Furthermore, treatment of MARVELD1 unexpressing Hep3B2.1-7 and PLC/PRF/5 cells with the demethylating agent 5-aza-2' deoxycytidine restored its expression. Overexpression of MARVELD1 suppressed the proliferation of HCC cells in vitro and in vivo, whereas downregulation of endogenous MARVELD1 by shRNAs significantly enhanced these characters. MARVELD1 overexpression could enhance chemosensitivity of HCC cells to epirubicin and 10 hydroxycamptothecin. Corresponding to these results, the expression of p-ERK1/2 and cyclin D1 were decreased, whereas p16 and p53 were increased in MARVELD1 transfected cells. We also demonstrated that knockdown of MARVELD1 resulted in upregulation of p-ERK1/2 and cyclin D1, and downregulation of p16 and p53. Moreover, the effect of the decreased cell growth rate was significantly reversed when MARVELD1-overexpressing cells were trasfected with p53 or p16 siRNA. Our findings suggest that MARVELD1 is a tumor suppressor by negatively regulating proliferation, tumor growth and chemosensitivity of HCC cells via increasing p53 and p16 in vitro and in vivo. MARVELD1 may be a potential target for HCC therapy. PMID- 22320885 TI - Link between inflammation and aquaporin-5 distribution in submandibular gland in Sjogren's syndrome? AB - OBJECTIVE: To determine whether a link exists between inflammation and aquaporin 5 distribution in submandibular glands from three animal models for Sjogren's syndrome: IQI/JIC, r1DeltaT/r2n and non-obese diabetic mice. METHODS: Mice of different ages were used. Inflammatory infiltrates were quantified using the focus score. Acinar aquaporin-5 subcellular distribution was determined by immunohistochemistry and quantified using labelling indices. RESULTS: Minor inflammatory infiltrates were present in r1f/r2n mice. Massive inflammatory infiltrates and acinar destruction were observed in 24-week-old non-obese diabetic mice, 10-and 13-month-old IQI/JIC mice and some r1DeltaT/r2n mice. Aquaporin-5 immunoreactivity was primarily apical in submandibular glands from 8- and 24-week-old Balb/C mice, 8-week-old non-obese diabetic mice, 2-, 4- and 7 month-old IQI/JIC mice and r1f/r2n mice. In contrast, decreased apical aquaporin 5 labelling index with concomitant increased apical-basolateral, apical cytoplasmic and/or apical-basolateral-cytoplasmic aquaporin-5 labelling indices was observed in 24-week-old non-obese diabetic, 10- and 13-month-old IQI/JIC and r1DeltaT/r2n mice with a focus score>=1. CONCLUSIONS: Altered aquaporin-5 distribution in submandibular acinar cells from IQI/JIC, non-obese diabetic and r1DeltaT/r2n mice with a focus score>=1 appears to be concomitant to the presence of inflammatory infiltrates and acinar destruction. PMID- 22320886 TI - Paramagnetic palladacycles with Pd(III) centers are highly active catalysts for asymmetric aza-Claisen rearrangements. AB - A combination of spectroscopic and electrochemical methods--XANES, EXAFS, X-ray, (1)H NMR, EPR, Mossbauer, and cyclic voltammetry--demonstrate that the most efficient Pd catalysts for the asymmetric rearrangement of allylic trifluoroacetimidates unexpectedly possess in the activated oxidized form a Pd(III) center bound to a ferrocene core which remains unchanged (Fe(II)) during the oxidative activation. These are the first recognized Pd(III) complexes acting as enantioselective catalysts. PMID- 22320887 TI - A British view on the Italian guidelines on urinary tract infection in young children. PMID- 22320888 TI - Determination of the shell permeability of microcapsules with a core of oil-based active ingredient. AB - An experimental and theoretical methodology is proposed to calculate the permeability of microcapsules that contain a core of oil-based active ingredient. Theoretical analysis is performed considering the polydispersity of the measurable capsule size, which allows the estimation of the permeability polydispersity via three different methods. The models proposed were applied in order to determine the permeability of melamine-formaldehyde microcapsules with hexyl salicylate as core oil. Release experiments were performed with four different co-solvents (ethanol, propan-1-ol, propan-2-ol and 1,3-butanediol) of different concentration. Permeability values were found to be constant, despite a two order magnitude of difference in the solubility concentrations. PMID- 22320889 TI - Feeding difficulties in children with inherited metabolic disorders: a pilot study. AB - BACKGROUND: In children with inherited metabolic disorders (IMD), feeding difficulties are often assumed to be inherent, although there is little evidence describing their frequency or severity. The present study aimed to describe feeding patterns/difficulties among children with IMD on protein-restricted diets from one centre. METHODS: Data from an observational, pilot study of 20 IMD children, nine females (median age, 2.7 years; range, 1-6 years) were compared with data obtained from a retrospective historical group of 15 healthy children (HC), 12 females, aged 1-5 years (median 3.0 years). Caregivers completed a feeding assessment questionnaire, and three separate video recordings were taken of each child eating at home. RESULTS: The main feeding problems identified by the caregivers' questionnaire in the IMD group (compared to HC) were: poor appetite (55% versus 7%; P = 0.004), limited food variety (55% versus 27%; P = 0.04) and lengthy mealtimes (70% versus 20%; P = 0.006). During mealtimes, children from the IMD group were more likely to vomit, exhibit negative behaviour, get distracted and self-feed less often. From video recordings of meals, although the median meal duration was similar for the two groups (18 min IMD versus 16 min HC), the HC ate twice the quantity of food (3.4 mouthfuls min( 1) versus 1.5 mouthfuls min(-1) ; P < 0.001). During mealtimes, IMD caregivers were less likely to talk to their children (median parent to child communications: IMD group, seven in 10 min; HC, 17 in 10 min). Eighty-three percent of IMD children regularly ate alone. CONCLUSIONS: In children with IMD on protein restrictions, severe feeding difficulties were common. Caregivers need to focus more attention on the social aspects of feeding. Further larger scale studies are required. PMID- 22320890 TI - Nanomaterial transformation and association with fresh and freeze-dried wastewater activated sludge: implications for testing protocol and environmental fate. AB - Engineered nanomaterials (ENMs) are an emerging class of contaminants entering wastewater treatment plants (WWTPs), and standardized testing protocols are needed by industry and regulators to assess the potential removal of ENMs during wastewater treatment. A United States Environmental Protection Agency (USEPA) standard method (OPPTS 835.1110) for estimating soluble pollutant removal during wastewater treatment using freeze-dried, heat-treated (FDH) activated sludge (AS) has been recently proposed for predicting ENM fate in WWTPs. This study is the first to evaluate the use of FDH AS in batch experiments for quantifying ENM removal from wastewater. While soluble pollutants sorbed equally to fresh and FDH AS, fullerene, silver, gold, and polystyrene nanoparticles' removals with FDH AS were approximately 60-100% less than their removals with fresh AS. Unlike fresh AS, FDH AS had a high concentration of proteins and other soluble organics in the liquid phase, an indication of bacterial membrane disintegration due to freeze drying and heat exposure. This cellular matter stabilized ENMs such that they were poorly removed by FDH AS. Therefore, FDH AS is not a suitable sorbent for estimating nanoparticle removal in WWTPs, whereas fresh AS has been shown to reasonably predict full-scale performance for titanium removal. This study indicates that natural or engineered processes (e.g., anaerobic digestion, biosolids decomposition in soils) that result in cellular degradation and matrices rich in surfactant-like materials (natural organic matter, proteins, phospholipids, etc.) may transform nanoparticle surfaces and significantly alter their fate in the environment. PMID- 22320891 TI - Spatial and temporal patterns of neutral and adaptive genetic variation in the endangered African wild dog (Lycaon pictus). AB - Deciphering patterns of genetic variation within a species is essential for understanding population structure, local adaptation and differences in diversity between populations. Whilst neutrally evolving genetic markers can be used to elucidate demographic processes and genetic structure, they are not subject to selection and therefore are not informative about patterns of adaptive variation. As such, assessments of pertinent adaptive loci, such as the immunity genes of the major histocompatibility complex (MHC), are increasingly being incorporated into genetic studies. In this study, we combined neutral (microsatellite, mtDNA) and adaptive (MHC class II DLA-DRB1 locus) markers to elucidate the factors influencing patterns of genetic variation in the African wild dog (Lycaon pictus); an endangered canid that has suffered extensive declines in distribution and abundance. Our genetic analyses found all extant wild dog populations to be relatively small (N(e) < 30). Furthermore, through coalescent modelling, we detected a genetic signature of a recent and substantial demographic decline, which correlates with human expansion, but contrasts with findings in some other African mammals. We found strong structuring of wild dog populations, indicating the negative influence of extensive habitat fragmentation and loss of gene flow between habitat patches. Across populations, we found that the spatial and temporal structure of microsatellite diversity and MHC diversity were correlated and strongly influenced by demographic stability and population size, indicating the effects of genetic drift in these small populations. Despite this correlation, we detected signatures of selection at the MHC, implying that selection has not been completely overwhelmed by genetic drift. PMID- 22320892 TI - Concordance of HER2 status assessed on needle core biopsy and surgical specimens of invasive carcinoma of the breast. AB - AIMS: Human epidermal growth factor receptor 2 (HER2) status of invasive breast cancers is vital for selection of patients for trastuzumab treatment. This study aimed to assess the level of agreement of HER2 status in core biopsy and excision specimens using immunohistochemistry, with in-situ hybridisation for equivocal cases. METHODS AND RESULTS: 300 consecutive invasive carcinomas with core biopsy and surgical specimens had HER2 assessed on both specimens. Immunohistochemistry was performed first. Fluorescence in-situ hybridization (FISH) was automatically performed if the immunohistochemistry was scored as equivocal (2+). There was agreement between the HER2 status of the two specimens in 294 tumours (98%). In two carcinomas the core was negative and the excision specimen showed focal strong staining with amplification. In four carcinomas the core biopsy was negative and the excision showed 2+ staining with amplification in at least one block (although in three there was no amplification in a second block). CONCLUSION: There is excellent agreement between HER2 assessed in core biopsy and surgical specimens. Discrepancies arise most frequently due to focal amplification or levels of gene amplification around the cut-off for defining positivity. PMID- 22320893 TI - Spectral analysis of target-appropriate /t/ and /k/ produced by phonologically disordered and normally articulating children. AB - Previous research (Forrest, Weismer, Hodge, Dinnsen and Elbert, 1990) has shown that some phonologically disordered children differentially mark seemingly homophonous phonemes; however, the resulting contrast may be spectrally distinct from that produced by normally articulating children of the same age. In the present investigation possible sources for these differences between normally articulating and phonologically disordered children's productions of target appropriate phonemes were pursued. Spectral characteristics of seemingly correct productions of /t/ and /k/ in word-initial position were analysed for four normally articulating and seven phonologically disordered children to assess the effect of recency of acquisition, depth of knowledge of the contrast and/or the effect of a phonological disorder on accuracy and variability of production. Results revealed that children who had acquired the velar-alveolar contrast more recently, and who had incomplete knowledge of that contrast, produced target appropriate /t/ and /k/ differently from their normally articulating peers and other phonologically disordered children with greater knowledge of the contrast. Further, the phonologically disordered children with incomplete knowledge of the velar-alveolar contrast were less variable than the other phonologically disordered or normally articulating children in the spectral characteristics across repeated productions. Analysis of the spectral characteristics of word initial /t/ and /k/ at a later point in time indicated similarities between all speaker groups in the spectral parameters that distinguished the velar from the alveolar stop. However, the stability of these parameters across repeated productions decreased for the phonologically disordered children with greater knowledge of the contrast. These effects are related to motor skill development and found to be consistent with previously demonstrated patterns of skill acquisition. PMID- 22320894 TI - The substitution of a click for sibilants: a case study. AB - In the case study presented in this paper a 4-year-old English-speaking girl showed an unusual phonological pattern of substituting a dental click for the sibilants /s, z, ?, I, t?, dI/. After two intervention sessions this pattern was eliminated from her speech and all the sibilants were produced correctly. In addition to providing an example of a child's contrastive use of a non-English segment, this case study provides evidence of a child's selection of a sound substitute on the basis of its auditory rather than articulatory similarity to the target phonemes. The rapid rate of change observed in the child's phonological system seems consistent with a phonological learning model in which the child has adult-like underlying phonological representations. PMID- 22320895 TI - Consonant inventories of young children from 8 to 25 months. AB - The results of a longitudinal study of seven children's consonant production are reported. Data were collected at monthly intervals between the ages of 8 and 25 months. All glossable and non-glossable utterances that occurred during data collection were combined to determine: (1) the number and types of consonants occurring in the children's syllable-initial and syllable-final inventories, and (2) the relative frequency of occurrence of the major manner and place sound classes. The results were comparable to those of previous investigations, although slightly larger and more diverse consonant types were noted in the children's earliest monthly inventories. The advantages of considering non glossed vocalizations when assessing a young child's phonetic abilities are discussed. PMID- 22320896 TI - Repetitiveness in language disorders: a new analytical procedure. AB - A common feature of a wide range of language disorders is the tendency to repeat a particular linguistic form-or set of forms-with abnormal frequency. A brief overview is given of the different ways in which disordered language can be repetitive, and the nature of stereotyped and repetitive language is discussed in terms of the reciprocal relationship between frequency of occurrence and productivity. It is argued that measures such as lexical type-token ratio provide only a partial picture of repetitive language, and that linguistic units larger than the word also need to be taken into consideration. An analytical framework incorporating such units is proposed, which is able to characterize and quantify the extent to which a sample of language is repetitive independently of its aetiology. An illustrative analysis is given of a language sample from a brain damaged adult, and the repetitiveness profiles of four different patients are compared. PMID- 22320898 TI - Involvement of angiotensin II type 1 receptor on pathological remodeling and dysfunction in obstructed bladder. AB - OBJECTIVES: To determine whether long-term administration of an angiotensin II type 1 receptor antagonist improves morphology and function in obstructed bladders. METHODS: Male Sprague-Dawley rats underwent surgery to produce bladder outlet obstruction (bladder outlet obstruction group; n = 32) or sham surgery (sham group; n = 16). A total of 2 weeks later, 16 bladder outlet obstruction rats were given the AT1 antagonist, candesartan, subcutaneously (candesartan group) using an osmotic pump for 4 weeks; the remaining bladder outlet obstruction-rats received vehicle (bladder outlet obstruction group). A total of 6 weeks after surgery, we compared continuous cystometry, bladder weight, strip contraction, histology and messenger ribonucleic acid expression of growth factors, nicotinamide adenine dinucleotide phosphate oxidase 1 and renin angiotensin system components among the three groups. RESULTS: Bladder weights markedly increased with bladder outlet obstruction (578 +/- 159 mg), and candesartan (344 +/- 111 mg) suppressed this increase. Micturition pressure, which was significantly higher with bladder outlet obstruction, was unaffected by candesartan. The shortened micturition interval and decreased micturition volume with bladder outlet obstruction were significantly prolonged and increased by candesartan. Candesartan also significantly decreased residual urine. Histologically, the collagen fiber-to-muscle ratio was significantly increased with bladder outlet obstruction (0.85 +/- 0.25) compared with the sham group (0.53 +/- 0.18); this increase was suppressed by candesartan (0.49 +/- 0.21). The messenger ribonucleic acid expression of heparin-binding epidermal growth factor like growth factor, transforming growth factor-beta1 and nicotinamide adenine dinucleotide phosphate oxidase 1 significantly increased with bladder outlet obstruction, but it was significantly reduced by candesartan. Compared with the bladder outlet obstruction group, candesartan increased the maximal contraction of bladder strips for all stimuli except for angiotensin II. CONCLUSION: These findings suggest that bladder angiotensin II type 1 receptors contribute to the pathophysiology of remodeling and dysfunction in obstructed bladder. PMID- 22320899 TI - First Danish single-institution experience with radical prostatectomy: impact of surgical margins on biochemical outcome. AB - OBJECTIVE: This study aimed to investigate the impact of positive surgical margins (PSMs), stratified by location and extension, on biochemical outcome after radical retropubic prostatectomy (RRP). MATERIAL AND METHODS: The study included data from 605 consecutive patients treated with RRP for localized prostate cancer. Patients with node-positive disease were excluded. Biochemical recurrence-free survival was calculated using the Kaplan-Meier method. Univariate and multivariate analysis was used to assess risk factors. RESULTS: The overall PSM rate was 35.4%. Eighty-three per cent (82.7%) of these had a single PSM, whereas 17.3% of patients had two or more PSMs. Apical PSMs were present in 42.5% and non-apical in 57.5%. The presence of any PSM had a significant impact on the risk of biochemical recurrence (BR) [hazard ratio (HR) = 3.3, p < 0.0001]. Compared with margin-negative patients, both apical and non-apical PSMs increased the risk of BR (HR = 2.1 and 4.2, p = 0.02 and p < 0.0001, respectively). The number of PSMs also influenced the risk of BR (one PSM: HR = 2.8, p < 0.0001, vs two or more PSMs: HR = 5.5, p < 0.0001). In multivariate analysis, pT category, PSA and prostatectomy Gleason score independently increased the risk of BR. In an exploratory multivariate analysis of pT2 tumours, the impact of apical PSMs on biochemical recurrence-free survival (BRFS) was not statistically significant, although with an HR of 2.1. Non-apical PSM was associated with a significantly increased risk of BR (HR = 3.4, p = 0.01). Number of PSMs did not influence the risk of BR in multivariate analysis. CONCLUSION: The presence of PSMs after RRP is associated with a higher risk of BR. Multiple and non-apical PSMs are associated with a significantly higher risk of BR compared to single and apical PSMs. PMID- 22320900 TI - Diving through the "-omics": the case for deep phenotyping and systems epidemiology. AB - Enabled by diverse high-throughput technologies, the rapidly evolving field of " omics sciences" offers the potential to study health and disease in breadth and depth at the human population level. We have recently linked genomics and metabolomics to present the first genome-wide association study of metabolic traits in human urine providing new insights into the functional background of chronic kidney disease. We propose systems epidemiology as a novel approach to study the complexities of human pathophysiology by integrating various population level omic-metrics and to identify new trans-omic biomarkers. PMID- 22320901 TI - Large summer weight gain in relatively overweight preschool Japanese children. AB - BACKGROUND: Children's lifestyles have changed recently in Japan. These changes are thought to be associated with their physical growth. The aim of the present paper was to describe and interpret the growth seasonality of children attending day-nurseries in Osaka Prefecture, Japan. METHODS: Results were based on a 6 year follow-up study of preschool children aged 0 at baseline to 6 years old at the end of the follow up. Longitudinal growth data for 148 boys and 113 girls, born between April 1990 and March 1991, attending day-nursery were obtained monthly from April 1990 through to March 1996. Children were divided into two groups: those with a normal (<17) or high (>= 17) body mass index (BMI) at 5 years of age. Weight and height seasonal gains were estimated for each group. RESULTS: Weight gain was higher during autumn among the group with a normal BMI at 5 years of age. Among high BMI group, weight gain was higher during autumn when they were 0 to 4 years of age, while it was higher during summer when they were 5 years of age. Height gain was higher in spring and summer in both BMI groups. Results were similar in boys and girls. CONCLUSION: Although the findings are consistent with previous studies for normal BMI children, the present study reports new findings for children with a high BMI at 5 years of age, for whom a large weight gain occurred during summer. PMID- 22320902 TI - Faecal short chain fatty acids in healthy subjects participating in a randomised controlled trial examining a soluble highly viscous polysaccharide versus control. AB - BACKGROUND: Short chain fatty acids (SCFA) are produced by the bacterial fermentation of dietary fibre and have been linked with intestinal health. The present study examined faecal SCFA concentrations in subjects consuming a novel soluble highly viscous polysaccharide (HVP) or control for 3 weeks. A total of 54 healthy adults participated in a randomised, double-blind, placebo-controlled study. METHODS: Subjects were randomised to consume HVP or control (skim milk powder). A dose of 5 g day(-1) was consumed in the first week, followed by 10 g day(-1) in the second and third weeks (n = 27 per group). The primary outcome was SCFA concentrations in faecal samples collected at baseline (visit 1, V1), at 1 week (V2) and at 3 week (V3). RESULTS: The reduction in faecal acetate from V1 to V3 in control subjects was not observed in subjects consuming HVP. There were no differences in propionate, butyrate, valerate or caproate concentrations. There was a significant treatment effect (P = 0.03) for total SCFA, with higher concentrations observed in subjects consuming HVP versus control. CONCLUSIONS: HVP is a viscous functional fibre that may influence gut microbial fermentation. Further work is warranted to examine the fermentative properties of HVP and possible links with appetite regulation and reduced serum low-density lipoprotein cholesterol concentrations. PMID- 22320903 TI - Identification of a novel role of Septin 10 in paclitaxel-resistance in cancers through a functional genomics screen. AB - Paclitaxel (also known as taxol) is a member of the taxane class of anticancer agents, which has a well-known mechanism that blocks cell mitosis and kills tumor cells, that is often used in clinics to treat cancer. However, some carcinomas such as breast, ovarian and non-small-cell lung cancers are often resistant to paclitaxel treatment. In this study, we used a lentiviral siRNA library against the entire human genomes to identify genes associated with sensitivity to paclitaxel. We isolated two paclitaxel-resistant clones carrying the siRNA specific to septin 10 (SEPT10) and to budding uninhibited by benzimidazoles 3. The relation of budding uninhibited by benzimidazoles 3 to paclitaxel sensitivity has already been established, but that of SEPT10 remains unknown. Interestingly, overexpression of SEPT10 increased cells' sensitivity to paclitaxel; we also found that SEPT10 is an important regulator for microtubule stability. Furthermore, we found that paclitaxel-resistant tumors had decreased expression of SEPT10. Thus, SEPT10 may be a novel candidate molecule that acts as a good indicator of paclitaxel-resistant carcinomas. PMID- 22320909 TI - Obesity, autophagy and the pathogenesis of liver and pancreatic cancers. AB - Liver and pancreatic cancers are both highly lethal diseases with limited to no therapeutic options for patients. Recent studies suggest that deregulated autophagy plays a role in the pathogenesis of these diseases by perturbing cellular homeostasis and laying the foundation for disease development. While accumulation of p62 upon impaired autophagy has been implicated in hepatocellular carcinoma, its role in pancreatic ductal adenocarcinoma remains less clear. This review will focus on recent studies illustrating the role of autophagy in liver and pancreatic cancers. The relationships between autophagy, nuclear factor kappaB signaling and obesity in hepatocellular carcinoma will be discussed, as well as the dual role of autophagy in pancreatic ductal adenocarcinoma. PMID- 22320910 TI - Biological and clinical relevance of stem cells in pancreatic adenocarcinoma. AB - Cancer stem cells (CSC) have been identified in a growing number of human malignancies. CSC are functionally defined by their ability to self-renew and recapitulate tumors in the ectopic setting, and a growing number of studies have shown that they display other functional characteristics, such as invasion and drug resistance. These unique functional properties implicate a role for CSC in clinical consequences, such as initial tumor formation, relapse following treatment, metastasis, and resistance, suggesting they are a major factor in directing clinical outcomes. Pancreatic adenocarcinoma is a highly-aggressive disease with a propensity for early metastasis and drug resistance. Tumorigenic pancreatic cancer cells have been identified using the cell surface antigens CD44, CD24, and CD133, as well as the high expression of aldehyde dehydrogenase (ALDH). In vitro and in vivo studies have shown that ALDH- and CD133-expressing pancreatic CSC have a greater propensity for metastasis, and ALDH-expressing CSC have been shown to be resistant to conventional chemotherapy. In clinical samples from patients with resected pancreatic adenocarcinoma, the presence of ALDH expressing CSC was associated with worse overall survival. The development of CSC targeting therapies might be important in changing the clinical outcomes of patients with this disease, and others and we have begun to identify novel compounds that block CSC function. This review will discuss the biological and clinical relevance of CSC in pancreatic cancer, and will discuss novel therapeutic strategies to target them. PMID- 22320911 TI - Cancer stem cells generated by alcohol, diabetes, and hepatitis C virus. AB - Cancer stem cells (tumor-initiating stem-like cells: TISCs) are resistant to chemotherapy and are associated with metastatic hepatocellular carcinoma (HCC), which is commonly observed in hepatitis C virus (HCV)-infected patients with obesity or alcohol abuse. However, it is unknown whether the TLR4-NANOG pathway serves as a universal oncogenic signaling in the genesis of TISCs and HCC. We aimed to determine whether Tlr4 is a putative proto-oncogene for TISCs in liver oncogenesis due to different etiologies and how Tlr4 is regulated at the transcriptional and epigenetic levels. CD133+/CD49f+ TISCs were isolated using FACS from HCC developed in HCV Core Tg mice fed alcohol, diethylnitrosamine treated mice, and alcoholic patients with or without HCV infection. CD133+/CD49f+ cells isolated from the animal models and patients are tumorigenic both in vitro and in a xenograft model, and Tlr4 or Nanog silencing with shRNA attenuates their tumor initiating property. Functional oncogene screening of a cDNA library identified the organ size control pathway targets Yap1 and AKT activator Igf2bp3 as NANOG-dependent genes that inhibit transforming growth factor-beta signaling in TISCs. Tlr4 expression is higher in TISCs compared with CD133-/CD49f+ cells. Taken together, Tlr4 may be a universal proto-oncogene responsible for the genesis of TLR4-NANOG dependent TISCs, and this pathway serves as a novel therapeutic target for HCC. PMID- 22320912 TI - Bone marrow-derived proangiogenic cells in pancreatic cancer. AB - Tumor-derived signals systemically induce an angiogenic switch that allows cancer cells to survive and grow. However, the vascular network in tumors is not well organized and fails to meet metabolic needs to maintain tissue homeostasis, resulting in significant hypoxia. Among various tumors, pancreatic ductal adenocarcinoma (PDAC) typically develops in an unusually disordered microenvironment, which contributes to its highly aggressive behavior. Since anti vascular endothelial growth factor (VEGF) (Avastin) has failed to demonstrate a survival benefit in PDAC, we need to re-visit the basic biology of this disease and understand what makes it so refractory to the anti-angiogenic approaches that are clinically effective in other neoplasms. To address this issue, we specifically focused on the process of neovascularization where bone marrow derived cells (BMDCs) play a role during pancreatic tumorigenesis. We have identified subsets of BMDCs that regulate key processes during development of the neovessels through paracrine Hedgehog signaling. Considering the importance of systemic responses occurring in tumor bearing hosts, we are currently using genetically engineered mice, which spontaneously develop PDAC, Pdx1-Cre;LSL Kras(G12D);p53(lox/+) strain, to clarify critical events that can trigger aberrant angiogenesis in pancreatic cancer. These studies allow us to provide insights into the cellular and molecular mechanisms of pancreatic tumorigenesis and have an implication for the design of therapies against this difficult disease. PMID- 22320913 TI - Impaired autophagy and organellar dysfunction in pancreatitis. AB - Recent findings from our group, obtained on experimental in vivo and ex vivo models of pancreatitis, reveal that this disease causes a profound dysfunction of key cellular organelles, lysosomes and mitochondria. We found that autophagy, the main cellular degradative, lysosome-driven process, is activated but also impaired in acute pancreatitis because of its' inefficient progression/resolution (flux) resulting from defective function of lysosomes. One mechanism underlying the lysosomal dysfunction in pancreatitis is abnormal processing (maturation) and activation of cathepsins, major lysosomal hydrolases; another is a decrease in pancreatic levels of key lysosomal membrane proteins LAMP-1 and LAMP-2. Our data indicate that lysosomal dysfunction plays an important initiating role in pancreatitis pathobiology. The impaired autophagy mediates vacuole accumulation in acinar cells; furthermore, the abnormal maturation and activation of cathepsins leads to increase in intra-acinar trypsin, the hallmark of pancreatitis; and LAMP-2 deficiency causes inflammation and acinar cell necrosis. Thus, the autophagic and lysosomal dysfunctions mediate key pathologic responses of pancreatitis. On the other hand, we showed that pancreatitis causes acinar cell mitochondria depolarization, mediated by the permeability transition pore (PTP). Genetic (via deletion of cyclophilin D) inactivation of PTP prevents mitochondrial depolarization and greatly ameliorates the pathologic responses of pancreatitis. Further, our data suggest that mitochondrial damage, by stimulating autophagy, increases the demand for efficient lysosomal degradation and therefore aggravates the pathologic consequences of lysosomal dysfunction. Thus, the combined autophagic, lysosomal and mitochondrial dysfunctions are key to the pathogenesis of pancreatitis. PMID- 22320915 TI - Iron and steatohepatitis. AB - As the main iron storage site in the body and the main source of the iron regulatory hormone, hepcidin, the liver plays a pivotal role in iron homeostasis. A variable degree of hepatic iron accumulation has long been recognized in a number of chronic liver diseases. Both alcoholic and non-alcoholic steatohepatitis display increased iron deposits in the liver, with an hepatocellular, mesenchymal, or mixed pattern, and recent reports have documented a concomitant aberrant hepcidin expression that could be linked to different coincidental pathogenic events (e.g. the etiological agent itself, necroinflammation, metabolic derangements, genetic predisposition). The present study reviews the pathogenic mechanisms of iron accumulation in steatohepatitis during alcoholic and non-alcoholic liver disease and the role of excess iron in chronic disease progression. PMID- 22320914 TI - Alcohol, insulin resistance and the liver-brain axis. AB - Chronic alcohol exposure inhibits insulin and insulin-like growth factor signaling in the liver and brain by impairing the signaling cascade at multiple levels. These alterations produced by alcohol cause severe hepatic and central nervous system insulin resistance as the cells fail to adequately transmit signals downstream through Erk/mitogen-activated protein kinase (MAPK), which is needed for DNA synthesis and liver regeneration, and phosphatidylinositol 3 kinase (PI3K), which promotes growth, survival, cell motility, glucose utilization, plasticity, and energy metabolism. The robust inhibition of insulin signaling in liver and brain is augmented by additional factors involving the activation of phosphatases such as phosphatase and tensin homologue (PTEN), which further impairs insulin signaling through PI3K/Akt. Thus, intact insulin signaling is important for neuronal survival. Chronic alcohol consumption produces steatohepatitis, which also promotes hepatic insulin resistance, oxidative stress and injury, with the attendant increased generation of "toxic lipids" such as ceramides that increase insulin resistance. The PI3K/Akt signaling cascade is altered by direct interaction with ceramides as well as through PTEN upregulation as a downstream target gene of enhanced p53 transcriptional activity. Cytotoxic ceramides transferred from the liver to the blood can enter the brain due to their lipid-soluble nature, and thereby exert neurodegenerative effects via a liver-brain axis. We postulate that the neurotoxic and neurodegenerative effects of liver-derived ceramides activate pro inflammatory cytokines and increase lipid adducts and insulin resistance in the brain to impair cognitive and motor function. These observations are discussed in the context of insulin sensitizers as potential cytoprotective agents against liver and brain injury induced by alcohol. PMID- 22320916 TI - Differential roles of inflammatory cells in pancreatitis. AB - The incidence of acute pancreatitis per 100,000 of population ranges from 5 to 80. Patients suffering from hemorrhagic-necrotizing pancreatitis die in 10-24% of cases. 80% of all cases of acute pancreatitis are etiologically linked to gallstone disease immoderate alcohol consumption. As of today no specific causal treatment for acute pancreatitis exists. Elevated C-reactive protein levels above 130,mg/L can also predict a severe course of acute pancreatitis. The essential medical treatment for acute pancreatitis is the correction of hypovolemia. Prophylactic antibiotics should be restricted to patients with necrotizing pancreatitis, infected necrosis or other infectious complications. However, as premature intracellular protease activation is known to be the primary event in acute pancreatitis. Severe acute pancreatitis is characterized by an early inflammatory immune response syndrome (SIRS) and a subsequent compensatory anti inflammatory response syndrome (CARS) contributing to severity as much as protease activation does. CARS suppresses the immune system and facilitates nosocomial infections including infected pancreatic necrosis, one of the most feared complications of the disease. A number of attempts have been made to suppress the early systemic inflammatory response but even if these mechanisms have been found to be beneficial in animal models they failed in daily clinical practice. PMID- 22320917 TI - Regulation of transglutaminase-mediated hepatic cell death in alcoholic steatohepatitis and non-alcoholic steatohepatitis. AB - BACKGROUND AND AIM: Transglutaminase 2 (TG2), catalyzing crosslinking between lysine and glutamine residues, is involved in many liver diseases. We previously reported that TG2, induced in the nucleus of ethanol- or free fatty acids (FFAs) treated hepatic cells, crosslinks and inactivates a transcription factor Sp1, leading to reduced expression of c-Met and thereby caspase independent hepatic apoptosis in culture systems, animal models, and both alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH) patients. FFAs increase endoplasmic reticulum (ER) stress, NFkB activation and nuclear TG2 (nTG2) through pancreatic ER kinase (PERK)-dependent pathway, whereas ethanol induces nTG2 via retinoid signaling. However, the molecular mechanism by which ethanol/FFAs induce nuclear localization of TG2 has been unclear. METHOD: A similar nTG2-mediated cell death is induced in acyclic retinoid (ACR)-treated hepatocellular carcinoma. Using cultured cells, we investigated how to control this novel apoptotic pathway by regulating nuclear localization of TG2. RESULTS: TG2 is composed of N-terminal b-sandwich, catalytic core, b-barrel 1, and C-terminal b-barrel 2 domains. In a previous work, we identified a 14 amino acid nuclear localization signal (NLS) within the b-barrel 1 domain and a putative leucine-rich nuclear export signal (NES) at position 657 to 664 (LHMGLHKL) near the C-terminus in the b-barrel 2 domain, and found that ACR downregulated exportin-1 levels, thereby accumulation of TG2 in the nucleus. Here, we found that both ethanol and FFAs provoked generation of truncated short form of TG2 (TG2-S) defects in the putative NES at least in part through alternative splicing, thereby causing accumulation of TG2-S in the nucleus. CONCLUSION: The generation of TG2-S in ethanol or FFAs-treated hepatic cells is a novel therapeutic target for prevention of hepatic cell death associated with ASH/NASH. PMID- 22320918 TI - Pathophysiology guided treatment of nonalcoholic steatohepatitis. AB - Nonalcoholic fatty liver disease is a spectrum that ranges from benign steatosis to steatohepatitis. It has become the most common cause of chronic liver disease, and yet there continues to be a lack of effective therapeutic options. This article reviews current concepts underlying the pathophysiological basis of nonalcoholic steatohepatitis from development of insulin resistance to the establishment of fibrosis. Then using a physiology-based approach, specific targeted therapeutics are reviewed along with their drawbacks. The evidence behind current therapies is based predominantly on small trials and, thus, no recommendations can be made until larger randomized trials are conducted. PMID- 22320919 TI - What's new in liver fibrosis? The origin of myofibroblasts in liver fibrosis. AB - Chronic liver injury of many etiologies produces liver fibrosis and may eventually lead to the formation of cirrhosis. Fibrosis is part of a dynamic process associated with the continuous deposition and resorption of extracellular matrix, mainly fibrillar collagen. Studies of fibrogenesis conducted in many organs including the liver demonstrate that the primary source of the extracellular matrix in fibrosis is the myofibroblast. Hepatic myofibroblasts are not present in the normal liver but transdifferentiate from heterogeneous cell populations in response to a variety of fibrogenic stimuli. Debate still exists regarding the origin of hepatic myofibroblasts. It is considered that hepatic stellate cells and portal fibroblasts have fibrogenic potential and are the major origin of hepatic myofibroblasts. Depending on the primary site of injury the fibrosis may be present in the hepatic parenchyma as seen in chronic hepatitis or may be restricted to the portal areas as in most biliary diseases. It is suggested that hepatic injury of different etiology triggers the transdifferentiation to myofibroblasts from distinct cell populations. Here we discuss the origin and fate of myofibroblast in liver fibrosis. PMID- 22320920 TI - Dangerous liaisons: pancreatic stellate cells and pancreatic cancer cells. AB - One of the characteristic features of the majority of pancreatic ductal adenocarcinomas is an abundant desmoplastic/stromal reaction. Until recently, this stroma had received little attention from researchers studying the pathogenesis of pancreatic cancer, with most of the research focus resting on the biology of tumor cells themselves. However, evidence is now accumulating that the stroma plays a critical role in pancreatic cancer progression. The cells responsible for producing the stromal reaction in pancreatic cancer are activated pancreatic stellate cells (PSCs, the key effector cells in pancreatic fibrogenesis). In vitro and in vivo studies have convincingly demonstrated a close bi-directional interaction between PSCs and pancreatic cancer cells, which facilitates local tumor growth as well as distant metastasis. PSCs also interact closely with endothelial cells to stimulate angiogenesis and are possibly involved in the known resistance of pancreatic cancer to chemotherapy and radiation. Most interestingly, it has recently been shown that PSCs from the primary tumor can travel to distant metastatic sites where they likely facilitate the seeding, survival, and proliferation of cancer cells. Thus, it is now recognized that the stroma is an important alternative therapeutic target in this disease and concerted pre-clinical research is underway to develop strategies to modulate/deplete the stromal reaction to inhibit cancer progression. The challenge is to translate these developments into clinically applicable treatments for patients. PMID- 22320921 TI - Retinoic acids and hepatic stellate cells in liver disease. AB - Quiescent hepatic stellate cells (HSCs) in healthy liver store 80% of total liver retinols and release them depending on the extracellular retinol status. However, HSCs activated by liver injury lose their retinols and produce a considerable amount of extracellular matrix, subsequently leading to liver fibrosis. Emerging evidence suggests that retinols and their metabolites such as retinoic acids (RAs) contribute to liver regeneration, fibrosis and tumor. However, it is not clear yet why HSCs lose retinol, which enzymes are involved in the retinol metabolism of HSCs and what function of retinol metabolites on HSCs upon liver injury. Recently, our group and collaborators have demonstrated that during activation, HSCs not only lose retinols but also metabolize them into RAs by alcohol dehydrogenases and retinaldehyde dehydrogenases. As transcriptional factors, metabolized RAs induce retinoic acid early inducible-1 and suppressor of cytokine signaling 1 in HSCs, which plays an important role in the interaction between HSCs and natural killer cells. In addition, RAs released from HSCs may induce hepatic cannabinoid receptor 1 expression in alcoholic liver steatosis or regulate immune responses upon liver inflammation. The present review summarizes the role of endogenous metabolized RAs on HSCs themselves and on other liver cells including hepatocytes and immune cells. Moreover, the effects of exogenous retinol and RA treatments on HSCs and liver disease are discussed. PMID- 22320922 TI - Hepatic stellate cell progenitor cells. AB - Hepatic stellate cells (HSCs) are recognized as a major player in liver fibrogenesis. Upon liver injury, HSCs differentiate into myofibroblasts and participate in progression of fibrosis and cirrhosis. Additional cell types such as resident liver fibroblasts/myofibroblasts or bone marrow cells are also known to generate myofibroblasts. One of the major obstacles to understanding the mechanism of liver fibrogenesis is the lack of knowledge regarding the developmental origin of HSCs and other liver mesenchymal cells. Recent cell lineage analyses demonstrate that HSCs are derived from mesoderm during liver development. MesP1-expressing mesoderm gives rise to the septum transversum mesenchyme before liver formation and then to the liver mesothelium and mesenchymal cells, including HSCs and perivascular mesenchymal cells around the veins during liver development. During the growth of embryonic liver, the mesothelium, consisting of mesothelial cells and submesothelial cells, migrates inward from the liver surface and gives rise to HSCs and perivascular mesenchymal cells, including portal fibroblasts, smooth muscle cells around the portal vein, and fibroblasts around the central vein. Cell lineage analyses indicate that mesothelial cells are HSC progenitor cells capable of differentiating into HSCs and other liver mesenchymal cells during liver development. PMID- 22320923 TI - Novel anti-fibrotic modalities for liver fibrosis: molecular targeting and regenerative medicine in fibrosis therapy. AB - Based on the cellular and molecular mechanisms underlying hepatic fibrogenesis, several kinds of approaches have been proposed to treat liver fibrosis. Among a number of growth factors and cytokines that regulate collagen metabolism, transforming growth factor (TGF)-beta is the most potent factor to accelerate liver fibrosis by activating hepatic stellate cells, stimulating collagen gene transcription, and suppressing matrix metalloproteinases expression. Thus, TGF beta as well as its intracellular mediators, Smad proteins, can be potential therapeutic targets for liver fibrosis. Constitutive phosphorylation and nuclear accumulation of Smad3 is the common feature of activated stellate cells. We have synthesized a novel small compound that inhibits Smad3-dependent collagen gene transcription by promoting nuclear import of a transcriptional repressor, YB-1. Another insight into anti-fibrotic strategies is the contribution of bone marrow derived cells to the regression of liver fibrosis. Administration of granulocyte colony stimulating factor enhanced the migration of bone marrow-derived cells into fibrotic liver tissue and accelerated the regression of experimental liver fibrosis. We have recently identified novel unknown factors expressed by bone marrow-derived cells that not only ameliorate liver fibrosis but also accelerate regeneration of fibrotic liver. PMID- 22320924 TI - Hepatoprotective and anti-inflammatory cytokines in alcoholic liver disease. AB - The activation of innate immunity by various factors (e.g. lipopolysaccharide and complements) plays an important role in initiating and promoting alcoholic liver injury via the stimulation of Kupffer cells to induce oxidative stress and to produce pro-inflammatory cytokines (e.g. tumor necrosis factor [TNF]-alpha) that cause hepatocellular damage. Accumulating evidence suggests that the activation of innate immunity also stimulates Kupffer cells to produce the hepatoprotective cytokine interleukin-6 (IL-6) and the anti-inflammatory cytokine IL-10 during alcoholic liver injury. IL-6 protects against alcoholic liver injury via the activation of signal transducer and activator of transcription 3 (STAT3) and the subsequent induction of a variety of hepatoprotective genes in hepatocytes. IL-10 inhibits alcoholic liver inflammation via the activation of STAT3 in Kupffer cells/macrophages and the subsequent inhibition of liver inflammation. Recent studies have suggested that IL-10 may play a dual role in controlling ethanol induced steatosis and liver injury via the inhibition of the pro-inflammatory cytokine TNF-alpha, thereby ameliorating alcoholic liver injury, or via the inhibition of the hepatoprotective cytokine IL-6, thereby potentiating alcoholic liver injury. IL-22 is another important hepatoprotective cytokine that protects against acute and chronic alcoholic liver injury by binding to a receptor complex composed of IL-10R2 and IL-22R chains on the surfaces of hepatocytes. Finally, IL 22 treatment is a potential therapeutic option for treating severe forms of alcoholic liver disease because of its antioxidant, antiapoptotic, antisteatotic, proliferative, and antimicrobial effects, as well as the potential added benefit of few side effects. PMID- 22320926 TI - Granulocytapheresis and plasma exchange for severe alcoholic hepatitis. AB - BACKGROUND AND AIM: Severe alcoholic hepatitis (SAH) is an inflammatory response with multiple morbidity factors like leucocytosis, hepatomegaly, renal failure, hepatic encephalopathy, endotoxemia, and a high mortality rate. Identifying therapeutic interventions that can improve prognosis is the goal of research. METHODS: Questionnaires were sent to 1234 medical institutions asking for information on patients with SAH during 2004 to 2008, including patients' demography, disease profile and the therapeutic interventions patients had received during hospitalization. RESULTS: Forty-five hospitals had treated SAH patients, and provided full demographic data on 98 patients. Forty-eight patients had received no treatment, 12 patients had received granulocytes/monocytes apheresis (GMA) to deplete elevated myeloid lineage leucocytes, the rest had received one or more of the following treatments, corticosteroids, plasma exchange (PE) and hemodialysis (HD). Further, 38 patients had died and 60 had survived within 100 days of hospitalization. Serum creatinine (Cr) was higher in patients who had died versus patients who had survived (P = 0.001). Likewise, patients with white blood cells (WBC) >= 10(4)/uL had higher mortality rate versus patients with WBC < 10(4)/uL (P = 0.018). GMA in patients with WBC >= 10(4)/uL showed improved prognosis versus in patients with WBC >= 10(4)/uL who did not receive GMA (P = 0.0006). Corticosteroids, plasma exchange and HD did not significantly impact prognosis of SAH patients. CONCLUSIONS: Our perception is that, patients with elevated myeloid leucocytes benefit most from GMA, while plasma exchange appears to support patients with coagulation deficiency or high plasma bilirubin and HD has indication in patients with high Cr. PMID- 22320925 TI - Morphogens and hepatic stellate cell fate regulation in chronic liver disease. AB - Hepatic stellate cells (HSC) are the liver mesenchymal cell type which responds to hepatocellular damage and participates in wound healing. Although HSC myofibroblastic trans-differentiation (activation) is implicated in excessive extracellular matrix deposition, molecular understanding of this phenotypic switch from the viewpoint of cell fate regulation is limited. Recent studies demonstrate the roles of anti-adipogenic morphogens (Wnt, Necdin, Shh) in epigenetic repression of the HSC differentiation gene Ppargamma as a causal event in HSC activation. These morphogens have positive cross-interactions which converge to epigenetic repression of Ppargamma involving the methyl-CpG binding protein MeCP2. However, these morphogens expressed by activated HSC may also participate in cross-talk between HSC and hepatoblasts/hepatocytes to support liver regeneration, and their aberrant regulation may contribute to liver tumorigenesis. Implications of HSC-derived morphogens in these possibilities are discussed. PMID- 22320927 TI - Autologous bone marrow cell infusions suppress tumor initiation in hepatocarcinogenic mice with liver cirrhosis. AB - We have previously reported the efficacy and safety of autologous bone marrow cell infusion (ABMi) therapy for liver cirrhosis patients without hepatocellular carcinoma in a multicenter clinical trial. However, since liver cirrhosis is highly oncogenic, evaluation of the effects of ABMi on the mechanisms of hepatocarcinogenesis is of great importance. Therefore, frequent ABMi was performed in hepatocarcinogenic mice, and its effects on hepatocarcinogenesis were analyzed. The N-nitrosodiethylamine (DEN)/green fluorescent protein (GFP) carbon tetrachloride (CCl(4) ) model was developed by administering DEN once, followed by repeated administration of CCl(4) intraperitoneally as for the control group. In the administration (ABMi) group, GFP-positive bone marrow cells were infused through a tail vein. The kinetics of hepatocarcinogenesis were evaluated histologically 4.5 months after DEN treatment. At 4.5 months, there was significantly lower incidence of foci and tumors in the ABMi group, and they were smaller in number, while their size was almost equal. No GFP-positive tumors were found in ABMi livers. Moreover, ABMi livers showed significantly reduced liver fibrosis, consistent with significantly lower 8-hydroxy-2'-deoxyguanosine levels, higher superoxide dismutase activity, and increased nuclear translocation of nuclear factor-erythroid 2 p45-related factor 2. These results demonstrate that frequent ABMi might contribute to suppressed tumor initiation during stages of hepatocarcinogenesis, consistent with improvements in liver fibrosis and stabilization of redox homeostasis. PMID- 22320928 TI - Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients. AB - Decompensated liver cirrhosis (LC), a life-threatening complication of chronic liver disease, is one of the major indications for liver transplantation. Recently, mesenchymal stem cell (MSC) transfusion has been shown to lead to the regression of liver fibrosis in mice and humans. This study examined the safety and efficacy of umbilical cord-derived MSC (UC-MSC) in patients with decompensated LC. A total of 45 chronic hepatitis B patients with decompensated LC, including 30 patients receiving UC-MSC transfusion, and 15 patients receiving saline as the control, were recruited; clinical parameters were detected during a 1-year follow-up period. No significant side-effects and complications were observed in either group. There was a significant reduction in the volume of ascites in patients treated with UC-MSC transfusion compared with controls (P < 0.05). UC-MSC therapy also significantly improved liver function, as indicated by the increase of serum albumin levels, decrease in total serum bilirubin levels, and decrease in the sodium model for end-stage liver disease scores. UC-MSC transfusion is clinically safe and could improve liver function and reduce ascites in patients with decompensated LC. UC-MSC transfusion, therefore, might present a novel therapeutic approach for patients with decompensated LC. PMID- 22320929 TI - Alcohol, smoking, and obesity epidemiology in Japan. AB - The health impact of alcohol drinking, cigarette smoking and obesity differs between Asian and Western countries. The epidemiology of cancer and death related to these lifestyles are described in this article. In Japan, heavy alcohol drinking and cigarette smoking are rather high in men. While there is a worldwide anti-smoking policy, Japan is still on the way to aiming at this goal, and this delay in health promotion has maintained the high impact of smoking, whether active or passive, on people's health in that country. Public health policy should focus more strongly on the control of smoking and heavy drinking, especially among men. Maintaining the consumption of alcohol at a level below 46 g a day in men and 23 g a day in women appears to minimize the risks of mortality and cancer in the Japanese population. On the other hand, the obesity rate is low and being underweight is common both in men and women. Proportions of cancer attributable to a body mass index of 25 or more are only 0.5% in men and 1.1% in women. Given that many previous studies in Japanese and Asian populations have associated a low body mass index with an increased risk of cancer, the impact of being underweight--not only obese--may warrant further investigation. PMID- 22320930 TI - Epidemiology, risk factors, and the promotion of pancreatic cancer: role of the stellate cell. AB - There are approximately 277,000 new cases of pancreatic cancer and 266,000 deaths from pancreatic cancer annually, indicating a mortality rate of 96% of the cases diagnosed. Because of the ineffectiveness of therapies, a major emphasis needs to be placed on prevention. This paper reviews the epidemiology and risk factors for pancreatic cancer, and uses this information to propose plausible research directions for determining the biological mechanisms mediating the effects of risk factors on the promotion of pancreatic cancer, with a focus on the pancreatic stellate cell. PMID- 22320931 TI - Interactions of alcohol and tobacco in gastrointestinal cancer. AB - Cancer prevention is based on the identification of specific etiologic factors. Acetaldehyde derived from the alcoholic beverage itself and formed from ethanol endogenously has recently been classified by the International Agency for Research on Cancer/World Health Organization as a group 1 carcinogen to humans. This is based on the uniform epidemiological and biochemical evidence derived from individuals carrying alcohol and aldehyde dehydrogenase gene mutations. After drinking alcohol, these mutations are associated with increased exposure of the upper digestive tract to acetaldehyde and as well with a remarkably increased risk for upper gastrointestinal (GI) tract cancers. Acetaldehyde is the key intermediate in alcoholic fermentation and ethanol oxidation. Therefore, it is widely present in our environment. Furthermore, it is the most abundant carcinogenic compound of tobacco smoke. Most of the known risk factors for upper digestive tract cancer appear to be associated with an enhanced exposure of GI mucosa to locally formed acetaldehyde. In these process microbes, salivary glands and even mucosal cells appear to play an essential role. Consequently, in the presence of ethanol mutagenic acetaldehyde concentrations are found in the saliva, achlorhydric stomach and colon. Equal acetaldehyde concentrations are seen in saliva also during active smoking. ALDH2-deficiency and high active ADH1C result in two- to threefold salivary acetaldehyde concentrations after a dose of alcohol and this prevails for as long as ethanol is present in the blood and saliva. Regarding cancer prevention, the good news is that acetaldehyde exposure can be markedly reduced. This can be achieved by giving high priority for regulatory measures and consumer guidance. PMID- 22320932 TI - Regioselective synthesis of 1,2-dihydropyridines by rhodium-catalyzed hydroboration of pyridines. AB - Pyridine undergoes addition of pinacolborane at 50 degrees C in the presence of a rhodium catalyst, giving N-boryl-1,2-dihydropyridine in a high yield. The selective 1,2-hydroboration also takes place in the reactions of substituted pyridines. In the reaction of 3-substituted pyridines, 3-substituted N-boryl-1,2 dihydropyridines are formed regioselectively. PMID- 22320933 TI - Differences in relationships among sleep apnoea, glucose level, sleep duration and sleepiness between persons with and without type 2 diabetes. AB - Obstructive sleep apnoea is common in patients with diabetes. Recently, it was reported that short sleep duration and sleepiness had deleterious effects on glucose metabolism. Thereafter, several reports showed relationships between glucose metabolism and obstructive sleep apnoea, sleep duration or sleepiness. But the interrelationships among those factors based on recent epidemiological data have not been examined. We analysed data on 275 male employees (age, 44+/ 8years; body mass index, 23.9+/-3.1kg m(-2) ) who underwent a cross-sectional health examination in Japan. We measured fasting plasma glucose, sleep duration using a sleep diary and an actigraph for 7days, and respiratory disturbance index with a type 3 portable monitor for two nights. Fifty-four subjects (19.6%) had impaired glucose metabolism, with 21 having diabetes. Of those 21 (body mass index, 25.9+/-3.8kgm(-2) ), 17 (81.0%) had obstructive sleep apnoea (respiratory disturbance index>=5). Regarding the severity of obstructive sleep apnoea, 10, four and three had mild, moderate and severe obstructive sleep apnoea, respectively. The prevalence of obstructive sleep apnoea was greater in those with than without diabetes (P=0.037). Multiple regression analyses showed that the respiratory disturbance index independently related to fasting plasma glucose only in the diabetic subjects. In patients with diabetes, after adjustment for age, waist circumference, etc. sleep fragmentation had a greater correlation with fasting plasma glucose than sleep duration, but without significance (P=0.10). Because the prevalence of obstructive sleep apnoea is extremely high in patients with diabetes, sufficient sleep duration with treatment for obstructive sleep apnoea, which ameliorates sleep fragmentation, might improve fasting plasma glucose. PMID- 22320934 TI - Changes in entrapped gas content and hydraulic conductivity with pressure. AB - Water table fluctuations continuously introduce entrapped air bubbles into the otherwise saturated capillary fringe and groundwater zone, which reduces the effective (quasi-saturated) hydraulic conductivity, K(quasi), thus impacting groundwater flow, aquifer recharge and solute and contaminant transport. These entrapped gases will be susceptible to compression or expansion with changes in water pressure, as would be expected with water table (and barometric pressure) fluctuations. Here we undertake laboratory experiments using sand-packed columns to quantify the effect of water table changes of up to 250 cm on the entrapped gas content and the quasi-saturated hydraulic conductivity, and discuss our ability to account for these mechanisms in ground water models. Initial entrapped air contents ranged between 0.080 and 0.158, with a corresponding K(quasi) ranging between 2 and 6 times lower compared to the K(s) value. The application of 250 cm of water pressure caused an 18% to 26% reduction in the entrapped air content, resulting in an increase in K(quasi) by 1.16 to 1.57 times compared to its initial (0 cm water pressure) value. The change in entrapped air content measured at pressure step intervals of 50 cm, was essentially linear, and could be modeled according to the ideal gas law. Meanwhile, the changes in K(quasi) with compression-expansion of the bubbles because of pressure changes could be adequately captured with several current hydraulic conductivity models. PMID- 22320935 TI - Interaction of social support and psychological stress on anxiety and depressive symptoms in breast cancer patients. AB - PURPOSE: The aim of the present study was to assess the association of psychological stress and social support with anxiety and depressive symptoms in Chinese newly diagnosed breast cancer patients. METHODS: Four hundred and one patients with breast cancer were recruited. Their demographic characteristics, psychological stress and social support were determined with a structured questionnaire, and their anxiety and depressive symptoms were assessed with the Hospital Anxiety and Depression Scale. RESULTS: Psychological stressors caused by breast cancer diagnosed originated from five major sources, as determined by factor analysis. These included "Worrying about health being harmed, " "Fear of decline of physical function, " "Fear of work being harmed, " "Worry about daily life and social relationship being restricted, " and "Fear of family being harmed. " Hierarchical linear regression analysis indicated that, after adjusting for gender, age, marital status, educational level, and duration of illness, solid social support can alleviate such symptoms. CONCLUSIONS: The results of this study suggest that there are strong associations between patients' needs and psychological distress with newly diagnosed breast cancer. Social support might affect these associations in Chinese women with breast cancer. PMID- 22320936 TI - Patient satisfaction survey of a self-paid physical checkup program for cancer screening. AB - INTRODUCTION: Early disease detection is an effective way to control diseases. Government sponsored health screening programs show their health value by increasing numbers of participants each year. Self-paid physical checkup programs may complement these programs. The purpose of this study was to examine participants' satisfaction with a self-paid physical checkup program for cancer screening. METHODS: This cross-sectional study consisted of two surveys with qualitative and quantitative questionnaires. A random sample of 1000 participants was collected from those who attended the self-paid physical checkup program in two periods. Their needs and expectations with the program with five point scores were analyzed. RESULTS: Data were collected during the period of January to June, 2001 and again in 2011. The response rates were 93.8% and 59%, and the effective rates were 94% and 71.4%, respectively. The results indicated that participants' items needed and items wished to cancel were similar in both surveys. The self paid physical checkup program met the needs of participants concerning gastrointestinal, colorectal and abdomen examinations. In contrast, dental, eye and physical examinations, and HIV screening were viewed as less interesting by participants, because of the lack of immediate post-checkup cares or they were not at high risk. CONCLUSIONS: Self-paid physical checkup programs add value to free cancer screening for health maintenance and help provide good physician patient relationships, health education and post-checkup cares. PMID- 22320937 TI - Radioprotective effects of troxerutin against gamma irradiation in V79 cells and mice. AB - The purpose of this study was to determine radioprotective effects of troxerutin. Cell experiments were carried out to test the cytotoxicity of troxerutin on V79 cells and to observe effects on apoptosis caused by 60CO gamma rays. A model of 8 Gy ray-caused damage of mice was established to observe the effect that troxerutin has on the physical symptom of irradiated mice and to calculate the 30 day survival rate. It showed that troxerutin had no obvious cytotoxicity at the level of less than 20 MUg/ml; but had a redioprotective effect in dose-dependence on viability of V79 cells at the range of 0.2-5 MUg/mL irradiated by 5 Gy ray of 60CO gamma ray. After the 8 Gy irradiation, the mice lost some weight, were dried up in fur and feather, low spirit, awkward in movement, shrinking in body and handicapped in sight, while mice with troxerutin were much better. So it was clear that troxerutin could increase the 30-day survival rates of irradiated mice dramatically. These results collectively indicate that troxerutin is an effective radioprotective agent. PMID- 22320938 TI - HLA-B*07 is a high risk allele for familial cervical cancer. AB - AIM: The purpose of this study was to investigate 50 women from eight families with familial cervical cancer in Wufeng County, Hubei Province, China, a region with a high incidence of cervical cancer. Eighty-nine healthy women, of similar age, location and ethnicity, were selected as a control group. METHODS: Blood samples were collected from both groups, and HLA-A, HLA-B, and HLA-DRB1 genotypes were profiled with the Multi-Analyte Profiling system (xMAP) (Luminex HLA-SSO) using a WAKFlow HLA typing kit. Results were analyzed with Luminex HLA typing software and showed good stability, reproducibility and specificity. RESULTS: We found several high risk alleles in women with familial cervical cancer, that associated with the highest risk being HLA-B*07 (OR = 8.7, 95% CI = 1.8-41.1). CONCLUSIONS: HLA-B*07 is a high risk allele for cervical cancer, and has strong potential for use as a molecular biomarker. PMID- 22320939 TI - Epidemiologic risk factors for esophageal cancer development. AB - In retrospective studies of esophageal cancer (EC), cigarettes and hookah smoking, nass use (a chewing tobacco product), opium consumption, hot tea drinking, poor oral health, low intake of fresh fruit and vegetables, and low socioeconomic status have been associated with a higher risk of esophageal squamous cell carcinoma. Barrett's esophagus is clearly recognized as a risk factor for EC, and dysplasia remains the only factor useful for identifying patients at increased risk, for the development of esophageal adenocarcinoma in clinical practice. Here, we review the epidemiologic studies that have investigated the epidemiologic patterns and causes of EC. PMID- 22320940 TI - Opportunity for breast cancer screening in limited resource countries: a literature review and implications for Iran. AB - Young age at occurrence and advanced tumour stage at diagnosis should urge health policy makers to focus on strategies that will help to reduce breast cancer burden in Iran. However, fundamental knowledge to select the optimal control strategy is limited. In this review paper we summarize considerations for launching a successful mass screening program in Iran using a thorough search of the literature focusing on screening activities for breast cancer in limited resource countries (LRCs). The Pubmed and Web of Knowledge databases were used for literature searches with the terms "breast neoplasm' and "screening' in combination with "limited resource countries', or "developing countries'. In addition, the bibliographies of selected references were also searched and utilized. More than 200 articles were found from 2005 to June 2011, of which 96 met the inclusion criteria. Papers were reviewed and categorized as follows: necessity and adoption of screening guidelines in LRCs (n=44); pilot implementation and barriers to screening program in LRCs (n=25); knowledge and attitudes on breast cancer and screening behaviour in LRCs (n=27). The results of the reviewed studies show that the rising trend of breast cancer incidence in LRCs has made it a health priority. Financial constraints to implement mammography screening in LRCs promote the use of alternative but less accurate screening modalities such as physical breast examination. Starting a breast cancer screening program in LRCs faces several challenges related to country's resources status, health service capacity and community awareness. Conservative attitudes toward women, fatalism and misconception on breast cancer risk factors and screening behaviour could seriously prohibit women's participation. In conclusion, given the lack of quantitative information and implementation research on breast cancer control in Iran, our ability to give a clear advice for breast cancer screening in Iran is limited. Iran should adopt a tailor-made strategy for mass screening with great emphasis on reducing the number of advanced stage tumours or "down-staging'. Combination of two approaches, clinical breast examination (CBE) and mammography would be promising given the increased competence of health care professional and public awareness. Equally important, a control plan should be started small and expanded gradually. PMID- 22320941 TI - Clinical observations on safety and efficacy of OxyContin(r) administered by rectal route in treating cancer related pain. AB - OBJECTIVE: To determine the efficacy and adverse reactions of OxyContin(r) administered by rectal route in advanced cancer patients. METHODS: Patients were enrolled into this study in which OxyContin was administered by the rectal route. The visual analogue scale (VAS) was applied to score pain intensity, separated into five degrees. National Cancer Institute-Common Toxicity Criteria (NCI-CTC) were adopted to record the side effects. RESULTS: VAS scores were 10 before treatment, and decreased to 5-6 after OxyContin application by the rectal route.The main side effects were constipation, flatulence and fatigue,with no elevation of transaminases and creatinine. CONCLUSION: OxyContin admistered by rectal route is safe for advanced cancer patients with satisfactory pain control effects, thus deserving further clinical observation. PMID- 22320942 TI - Updated meta-analysis of NFkappaB1 -94ins/Delattg promoter polymorphism and cancer risk based on 19 case-control studies. AB - OBJECTIVE: Recently, a common insertion/deletion (-94insertion/deletion ATTG, rs28362491) polymorphism in the NFkappaB1 promoter region has been extensively investigated for association with cancer risk but the results have been inconsistent. In order to clarify the effect of the promoter polymorphism we performed an update meta-analysis of published case-control studies to better compare the results between studies. METHODS: Relevant studies were identified via a thorough literature search on Medline and Embase database (up to August 10, 2011). The odds ratio (OR) and 95% confidence interval (95%CI) were used to investigate the strength of the association. RESULTS: A total of 5,196 cases and 6,614 controls in 19 case-control studies from 16 publications were included in this meta-analysis. Overall, the variant genotypes were associated with a moderately decreased risk of all cancer types (OR =0.74, 95%CI =0.57-0.97 for DD versus II; OR =0.79, 95%CI =0.66-0.95 for DD versus II/ID). In the stratified analyses, significantly decreased risk was found among Asians (OR =0.52, 95%CI =0.42-0.65 for DD versus II; OR =0.74, 95%CI =0.66-0.83 for ID versus II; OR =0.64, 95%CI =0.53-0.78 for DD versus II/ID; OR =0.68, 95%CI =0.61-0.75 for DD/ID versus II). The validity of this association was further strengthened by the sensitivity analysis. No publication bias was observed in this study. CONCLUSIONS: Our results suggested that the -94deletion ATTG promoter polymorphism in NFkappaB1 gene might be associated with a decreased cancer risk, especially for Asian population. PMID- 22320943 TI - Awareness about pictorial warnings on tobacco products and its impact on tobacco consumers in Bellary, India. AB - BACKGROUND: In India, 800,000-900,000 people will die annually due to diseases attributable to tobacco. The government of India has taken several measures, including legislation to control tobacco intake. Display of pictorial warnings on tobacco products was one of the legislative measures taken under The Cigarettes and Other Tobacco Products Act (COTPA) enacted in 2003, intended to discourage the consumption of tobacco. OBJECTIVES: 1) To study the factors influencing awareness among tobacco consumers about the pictorial warnings used on tobacco products; 2) To study the impact of the current pictorial warnings on tobacco consumers. MATERIALS AND METHODS: A cross sectional study was conducted from January 2011 to June 2011 at Bellary city, Karnataka. Data were collected with pre-tested and pre-designed semi-structured proforma. Univariate and multivariate analyses were conducted using Epi-info version 3.4.3. RESULTS: In our study out of 600 subjects 435 (72.5%) had seen the pictorial warnings. Among them 111 (25.5%) had interpreted correctly and 63 (14.5%) had given a thought/ tried to reduce or quit tobacco consumption. Younger age group, better educational status, people from urban area, upper socio economic class, lesser duration (< 5 years) of tobacco usage were found to have significant association with awareness about pictorial warnings on tobacco products. However, the impact of pictures on reducing/quitting tobacco consumption was very low. CONCLUSION: Awareness and its impact on tobacco consumption are poor among our study subjects. There is an urgent need for reconsideration for more effective pictorial warnings. PMID- 22320944 TI - HOGG1 Ser326Cys polymorphism and susceptibility to head and neck cancer: a meta analysis. AB - PURPOSE: Several research groups have investigated the influence of the human 8 oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys polymorphism on head and neck cancer (HNC) susceptibility. However, the results remain inconclusive and controversial. We therefore conducted the present meta-analysis. METHODS: Relevant studies were identified through a search of PubMed databases until July 2011 and selected on the basis of established inclusion criteria for publications. RESULTS: A total of 8 case-control studies on the association of hOGG1 Ser326Cys polymorphism with HNC risk were included in the present meta analysis. Overall significant associations were observed (G allele vs. C allele: OR=1.49, 95%CI=1.08-2.05, P<0.01 for heterogeneity; GG vs.CC: OR=2.30, 95%CI=1.05 5.05, P<0.01 for heterogeneity; CG vs. CC: OR=1.40, 95%CI=1.03-1.90, P<0.01 for heterogeneity; dominant model (GG+CG vs. CC): OR=1.52, 95%CI=1.06-2.16, P<0.01 for heterogeneity; recessive model (GG vs. CG+CC): OR=2.04, 95%CI=1.05-3.96, P=0.01 for heterogeneity) after excluding the studies that were not in agreement with HWE. On performance of a subgroup meta-analysis by ethnicity, significant associations were found (G allele vs. C allele: OR=1.40, 95%CI=1.001-1.95, P<0.01 for heterogeneity; GG vs.CC: OR=2.30, 95%CI=1.05-5.05, P<0.01 for heterogeneity; recessive model (GG vs. CG+CC): OR=2.04, 95%CI=1.05-3.96, P=0.01 for heterogeneity) in Caucasian populations after excluding one study not in agreement with HWE. CONCLUSIONS: Our results suggested that the G allele might be associated with an increased risk of HNC in Caucasian populations. PMID- 22320945 TI - Survey-based cancer mortality in the Lao PDR, 2007-08. AB - BACKGROUND: The Lao PDR is a landlocked country with 5,920,000 inhabitants for which very few epidemiological studies on cancer have been performed. The aim of the present study was to examine cancer mortality in 2007-2008. METHODS: A descriptive cancer epidemiology protocol was designed with a data collection form and guideline for both demographics and list of all deaths from all 757 local Health Centers of 17 provinces/ cities. Five indicators, name, age, sex, date of death and the cause of death (ICD-10), were collected for each case. The age specific cancer mortality rate and ASRs per 100,000 were estimated. RESULTS: There were 448 cancer cases reported from Health Centers within 7 of 17 provinces/cities. Number of person-years was 654,459 for the two-year period. Cancer mortality rates of all sites (ASR) were 116.7 and 97.2 per 100,000 in males and females, respectively. The five most common cancers causing mortality per 100,000 were liver (52.2), followed by colorectal (19.0), lung (17.3), stomach (6.9), and leukemia-lymphoma (7.2) in males and liver (28.4); followed by colorectal (19.0), lung (14.0), cervical uteri (9.2) and stomach (7.1) in females. CONCLUSIONS: Liver and colorectal cancers were the first and second most common, respectively, in both males and female. PMID- 22320946 TI - Induction of mitochondria-mediated apoptosis in human gastric adenocarcinoma SGC 7901 cells by kuraridin and Nor-kurarinone isolated from Sophora flavescens. AB - The study was designed as one of a series to find novel anticancer compounds from Chinese herbs. For this purpose, we screened an ethanol extract of 300 herbs against SGC-7901 cells. Sophora flavescen was included in those showing potential cytotoxic activity. Target compounds were therefore isolated and analyzed on analytical HPLC. Chromatography showed only one peak with a purity of 97%. The ESI-MS spectrum showed two molecular ions: m/z 424(M+) and 438(M+). Furthermore, combining the data of 1HNMR and 13CNMR, it was deduced that this product was a mixture of two compounds; kuraridin (1) and nor-kurarinone (2). The concentration was [1]:[2]=9:10, the chemical structural formulae are C25H28O6 and C26H30O6. In this study, mechanisms involved by the mixture of compounds 1 and 2-induced growth inhibition including apoptosis and G2/M phase arrest in human gastric adenocarcinoma SGC-7901 cells were examined for the first time. Triggering of the mitochondrial apoptotic pathway was demonstrated by loss of mitochondrial membrane potential, reduction in the Bcl-2/Bax ratio, and significant activation and cleavage of caspase-3. Additionally, the production of reactive oxygen species (ROS) was also increased. Taken together, our results indicated that the cytotoxic efficacy of the mixture of compounds 1 and 2 is mainly due to induction of cell cycle arrest and apoptosis. PMID- 22320947 TI - Epidemiology of oral and pharyngeal cancers in Khon Kaen, Thailand: a high incidence in females. AB - BACKGROUND: This study was aimed to describe incidence, trends, and survival of oral and pharyngeal cancers in Khon Kaen, the province situated in the northeast of Thai-land. METHODS: Data on oral and pharyngeal cancer cases diagnosed during 1985 - 2001 were retrieved from the population-based cancer registry of Khon Kaen. The final status of the patients was verified by database linkage and follow-up using postcards. RESULTS: Of 1,038 cases, 62.6% were female and 37.4% were male, with a mean age of 63 years. The age-standardized incidence rate (ASR) in females (6.2 per 100 000; 95%CI 5.7-6.7) was significantly higher than in males (3.9 per 100 000; 95%CI 3.5-4.4). Annual percent changes in ASR were 1.7 in females (p<0.05), but 1.2 in males. Lip and buccal cancers were the most common sites respectively; however, the incidence of tongue cancer was increasing in the last period. Eighty five percent of all cases were diagnosed in advanced stage (stage III and IV). The overall five-year relative survival was 43.1%. We found stage distribution and survival did not change during the study period. CONCLUSION: The considerably high incidence in female suggests a need for research on specific risk factors. Moreover, attempts should be made to detect oral cancers earlier in order to improve the outcomes of cancer control. PMID- 22320948 TI - Effects of aging and ethnicity on serum free prostate specific antigen. AB - Understanding the relationship between ethnicity and free prostate specific antigen (fPSA) could identify the population that should be targeted for intervention and prevention program regarding prostate disease. In this study, we therefore examine the effects of aging and ethnicity on fPSA, measured in serum by chemiluminescent assay (CLIA) method of 351 men visiting Tribhuvan University Teaching Hospital (TUTH) for fPSA test from December to March. Medicinal records abstracts were used to obtain information regarding the ethnicity and age of the cases. Those cases whose age and surname could not be obtained were excluded in our study. The subjects were stratified in four ethnic groups viz; Indo-Nepalese, Tibeto-Nepalese, Indigenous and Other based on the origin. The relationship between age and fPSA level was analysed using bivariate coorelation. The age and the fPSA level of the cases were expressed in Mean +/- SEM. The association among different age-group and ethnicity with fPSA were analysed using one way ANOVA. The mean fPSA and mean age of the subjects were 1.74 +/- 0.22 and 66.84 +/- 0.64 respectively. fPSA level was fairly correlated with the age (r=0.146, p=<0.01). The mean fPSA level (ng/ml) among the four age category (<45, 45-60, 60-75 and >75) were 0.49 +/- 0.13, 0.69 +/- 0.10, 1.94 +/- 0.04 and 2.33 +/- 0.43 respectively. The difference in mean fPSA level among four different age-groups was statistically significant (p=0.031). Analysis showed no correlation between the fPSA level and the ethnicity. These data suggest that the fPSA level is associated with the age. PMID- 22320949 TI - Cytoprotective activity of a trans-chalcone against hydrogen peroxide induced toxicity in hepatocellular carcinoma (HepG2) cells. AB - Dietary flavonoids have attracted attention as chemopreventive agents. Chalcones are abundantly present in nature starting from ferns to higher plants. Chemically 1,3-diphenyl-2-propen-1-ones, these are often cytotoxic in vitro. The cellular defense system (including glutathione, glutathione-related enzymes, and antioxidant and redox enzymes) plays a crucial role in cell survival and growth in aerobic organisms. In the present study, we aimed to evaluate the modulatory effect of trans-chalcone on protection from oxidative stress caused by hydrogen peroxide (H2O2) in hepatocellular carcinoma (HepG2) cells. Cell growth was evaluated by the 3-(4,5-dimethyl thiazol-2- yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Sub-toxic concentrations of compound (20 uM) increased cell survival and a decreased lipid peroxidation. The drug also decreased the H2O2 induction of glutathione related enzymes. Our results support the efficacy of trans-chalcone in offering protection against oxidative stress. PMID- 22320950 TI - Lateral lymph node dissection with radical surgery versus single radical surgery for rectal cancer: a meta-analysis. AB - OBJECTIVES: To assess the value of lateral lymph node dissection( LLND) in the radical surgery of rectal cancer. METHODS: The published Chinese and English literature was retrieved. A total of 15 papers fitted the selection criteria, including 4,858 patients. Among them 2,401 were in the LLND group and 2,457 in the non- LLND (NLLND) group. Evaluation parameters included 5-year survival rate recurrence rate, peri-operative outcomes, postoperative urinary and sexual functions. RESULTS: The operating time was significantly shorter in the NLLND group than that in the LLND group (weighted mean difference (WMD)=109 min, 95 confidence interval(CI):90-129, P <0.001). Intra-operative blood loss was greater in the LLND group, but the difference was not significant (WMD=429 mL, 95 CI:325 854, P = 0.05).The frequency of peri-operative morbidity(OR, 1.57 95 CI:1.06 2.33, P = 0.02) was also significantly higher in the LLND group. There were no significant differences in 5-year survival rate and recurrence rate between the two groups. Data from individual studies(three)showed that the frequency of male urinary dysfunction (OR=5.12, 95CI 2.15-12.19, P=0.0002) and sexual dysfunction (P < 0.05) were greatly lower in the NLLND group. CONCLUSION: Meta analysis showed that LLND did not have specific advantage in decreasing postoperative recurrence and prolonging survival time. Furthermore it was associated with prolonged operation time, increased blood loss and elevated incidence of peri operative complications and urinary and sexual dysfunction. PMID- 22320951 TI - Awareness and knowledge of breast cancer and mammography among a group of Malaysian women in Shah Alam. AB - OBJECTIVES: The aim of this study was to assess awareness and knowledge of breast cancer and mammography among Malaysian women in Shah Alam. METHODS: This cross sectional study was conducted among 250 Malaysian women. Data were collected using a self administrated questionnaire which included questions on socio demographic data, knowledge of breast cancer and awareness of mammography. RESULTS: Mean age of respondents was 28 +/- 9.2 with 69.2% aged 18 to 29 years. The majority had heard about breast cancer (81.2%) and indicated books, magazines and brochures as their source of information (55.2%). However, most did not know about signs and symptoms of breast cancer and many of its risk factors. On multivariate analysis, significant predictors of breast cancer knowledge were age, race, marital status, level of education, occupation, family size and family history of other cancers (p<0.05). Fifty percent of women were aware of mammography, significant predictors being age, occupation, marital status and knowledge of breast cancer (p<0.05). CONCLUSION: Most women were aware of breast cancer. However, the knowledge about signs and symptoms of breast cancer and awareness of mammography were inadequate. It is recommended that the level of knowledge should be raised among Malaysian women, particularly in the less educated young. PMID- 22320952 TI - A qualitative study on HPV vaccination from a nursing perspective in Hong Kong. AB - OBJECTIVE: To identify the perception on human papillomavirus (HPV) vaccination among female nursing students in Hong Kong. DATA SOURCES: Data were collected through focus group discussions and semi-structured in-depth interviews. All participants (n=28) were female nursing students of a university in Hong Kong. Tape recordings of individual interviews and focus group discussions were transcribed verbatim in Chinese, translated into English, and analyzed according to Colaizzi's phenomenological analysis. STUDY DESIGN: Four major themes emerged from the data: nursing students' understanding about HPV vaccine, nursing students' attitude on HPV vaccine, nursing students' perspective on HPV vaccination promotion, and nursing role on HPV vaccination. CONCLUSIONS: Government should take initiative in promotion with vaccine suppliers. The awareness and knowledge of HPV and HPV vaccination among women should be increased in order to raise the positive attitude of women towards HPV vaccination and prevention of cervical cancer. Health professionals should work together on HPV promotion among women and increase the HPV vaccination rates. Moreover, further studies regarding attitude and awareness of HPV vaccination among women in different age groups are needed in order to identify more associated factors affecting their perceptions towards HPV vaccination. PMID- 22320953 TI - Polymorphisms of DNA repair gene XRCC1 and risk of glioma: a case-control study in Southern China. AB - OBJECTIVE: This study aimed to examine associations between polymorphisms in the X-ray cross- complementing group 1 (XRCC 1) gene and risk of glioma in a Chinese population. METHODS: We performed a hospital-based case-control study with 271 cases and 289 controls in Guangdong province, China. Cases were patients newly diagnosed with pathologically confirmed glioma in two hospitals between June 2006 and May 2010. Controls were hospitalized individuals without cancer, frequency matched by sex and age. Three SNPs in XRCC1 gene, Arg399Gln (rs25487), Arg194Trp (rs1799782) and Arg280His (rs25489), were analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based method. Unconditional logistic regression was used to estimate the odds ratios (ORs) of polymorphisms in XRCC1 gene for glioma. RESULTS: The Arg399Gln polymorphism was significantly associated with risk of glioma. Individuals with the Gln/Gln genotype had a significantly increased likelihood of developing glioma compared with those with the Arg/Arg genotype (adjusted OR = 1.93, 95% CI: 1.04 - 3.58), especially among males and individuals aged 50 years or older. CONCLUSION: The XRCC1 Arg399Gln polymorphism may be a useful susceptibility biomarker for glioma. Further studies in Chinese populations with larger sample sizes are now warranted. PMID- 22320954 TI - Using salivary cotinine to validate self-reports of tobacco use by Indian youth living in low-income neighborhoods. AB - BACKGROUND: Self-reported tobacco use among young people can underestimate the actual prevalence of tobacco use. Biochemical validation of self-reports is particularly recommended for intervention studies where cessation outcomes are to be measured. Literature on biochemical validation of self-reports of multiple forms of tobacco use in India is sparse, particularly among young people. METHODS: The study was conducted during the baseline household survey of a community-based tobacco prevention and cessation intervention trial for youth (10 19 years old) residing in slum communities in Delhi, India in 2009. Salivary cotinine measurement on 1,224 samples showed that youth were under-reporting use of chewing and smoking tobacco. RESULTS: Self-reports had a low sensitivity (36.3%) and a positive predictive value of 72.6%. No statistically significant difference in under- reporting was found between youth in the control and intervention conditions of the trial, which will be taken into consideration in assessing intervention outcomes at a later time point. CONCLUSION: Biochemical validation of self-reported tobacco use should be considered during prevention and cessation studies among youth living in low-income settings in developing countries like India. IMPACT: The future results of biochemical validation from Project ACTIVITY (Advancing Cessation of Tobacco in Vulnerable Indian Tobacco Consuming Youth) will be useful to design validation studies in resource-poor settings. PMID- 22320955 TI - Effect of health belief model and health promotion model on breast cancer early diagnosis behavior: a systematic review. AB - Breast cancer is an important public health problem on the grounds that it is frequently seen and it is a fatal disease. The objective of this systematic analysis is to indicate the effects of interventions performed by nurses by using the Health Belief Model (HBM) and Health Promotion Model (HPM) on the breast cancer early diagnosis behaviors and on the components of the Health Belief Model and Health Promotion Model. The reveiw was created in line with the Centre for Reviews and Dissemination guide dated 2009 (CRD) and developed by York University National Institute of Health Researches. Review was conducted by using PUBMED, OVID, EBSCO and COCHRANE databases. Six hundred seventy eight studies (PUBMED: 236, OVID: 162, EBSCO: 175, COCHRANE:105) were found in total at the end of the review. Abstracts and full texts of these six hundred seventy eight studies were evaluated in terms of inclusion and exclusion criteria and 9 studies were determined to meet the criteria. Samplings of the studies varied between ninety four and one thousand six hundred fifty five. It was detected in the studies that educations provided by taking the theories as basis became effective on the breast cancer early diagnosis behaviors. When the literature is examined, it is observed that the experimental researches which compare the concepts of Health Belief Model (HBM) and Health Promotion Model (HPM) preoperatively and postoperatively and show the effect of these concepts on education and are conducted by nurses are limited in number. Randomized controlled studies which compare HBM and HPM concepts preoperatively and postoperatively and show the efficiency of the interventions can be useful in evaluating the efficiency of the interventions. PMID- 22320956 TI - The health seeking trajectories of Malaysian women and their husbands in delay cases of breast cancer: a qualitative study. AB - The aim of this study was to assess why women delay in getting treatment (i.e. surgery) for breast cancer, as well as to explore on what type of issues are involved in such delay cases. Basic interpretative of qualitative methodology was applied to construct the reality of delay phenomena, and its interaction with social worlds. Six themes were identified: new conception of breast cancer treatment, psychological defenses, health support system, symtomatology experience, model and barriers. The delay issue in breast cancer requires attention as a multidimensional problem as this will facilitate more comprehensive and effective intervention to reduce delay. PMID- 22320957 TI - Overexpression of Snail accelerates adriamycin induction of multidrug resistance in breast cancer cells. AB - In addition to several molecular and morphologic changes, epithelial-mesenchymal transition (EMT) cells also show variation in sensitivity to chemotherapeutics agents. The aim of this study was to investigate whether overexpression of Snail in MCF-7 cells is associated with facilitated acquisition of P-gp mediated multidrug resistance (MDR). The results demonstrated that over-expression of Snail indeed resulted in slight enhancement of adriamycin-induced MDR in MCF 7/Snail cells without detectable increase of P-gp. However, in the longer term, MCF-7 cells overexpressing Snail were prone to be resistant to adriamycin, in this case with increased expression of P-gp. These results provide evidence that a strategy involving Snail inhibition may be a useful and promising therapeutic aspect in modulating MDR. PMID- 22320958 TI - Clinical significance of mTOR and p-mTOR protein expression in human colorectal carcinomas. AB - AIM: To investigate the significance of mammalian target of rapamycin (mTOR) and its active form, p-mTOR in colorectal carcinomas. METHODS: Immunohistochemistry was used to detect the expression of mTOR and p-mTOR proteins in 108, 40 and 40 tissue samples from colorectal carcinoma, normal colonic mucosa and adenomatous polyps samples, respectively. The correlation of mTOR and p-mTOR expression with clinicopathological characteristics of colorectal carcinoma was analyzed. RESULTS: The positive rates of mTOR and p-mTOR were significantly higher in colorectal carcinoma (61.1% and 61.1%, respectively, p<0.05) than in normal colonic mucosa (7.5% and 2.5%) and adenomatous polyps (27.5% and 20%). Overexpression of total mTOR protein was significantly associated with T1/T2 stage tumors, lymph node metastasis, distal metastasis) and degree of differentiation. p-mTOR overexpression was additionaly linked with degree of differentiation and TNM stage. CONCLUSION: The overexpression of mTOR and p-mTOR may play important roles in colorectal carcinogenesis with relations to the degree of differentiation, invasiveness and metastasis. PMID- 22320959 TI - Needs for hepatocellular carcinoma control policy in the Asia-Pacific region. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is particularly burdensome in the Asia Pacific region, however, cross-country comparisons have been limited to somewhat unreliable epidemiological measures. We conducted a comparative needs assessment for HCC control policy to inform HCC control efforts in the Asia-Pacific region. The aims were to identify regional needs, to compare overall competence across the region, and to identify which needs were concordant across the region. METHOD: Using the self-explicated method, a stated-preference approach, clinical experts from Australia, China, Japan, Korea, Taiwan, and the United States valued ten previously identified dimensions of HCC control: clinical education; risk assessment; HBV strategy; HCV strategy; life-style risk factors; national statistics; funding for screening; funding for treatment; political awareness; and public awareness. Results were normalized and analyzed using Z-scores and ANOVA, with concordance of need across the region tested via the F-test. RESULTS: Seventy-two respondents, equally drawn from the study sites, completed the survey (response rate: 36%). Respondents were hepatologists (39%), oncologists (21%), radiologists (17%), surgeons (17%), and other specialists (7%) who were involved in liver cancer control at local/regional (35%) national (44%) or international (21%) levels. In aggregate, the most significant needs were political awareness, public awareness, and life-style risk factors (all p<0.001). Significant differences in aggregate competence were observed across the region (p<0.001), with better than expected competence reported by respondents from Taiwan (p<0.001), Japan (p=0.006), and Korea (0.041), and close to expected competence reported by respondents from Australia, China, and USA (all p>0.05). There were differences in the extent of needs across the region (p<0.05) on all dimensions except funding for screening, clinical education and life style risk factors. CONCLUSIONS: As the first comparative needs assessment for HCC for the Asia Pacific region, our results can inform national and cross-national priorities for intervention and facilitate the identification of best practices. Regional efforts to control HCC should adopt as objectives the needs for greater political and public awareness and improved management of lifestyle risk factors because these are the most significant needs, and are shared concerns across the region. PMID- 22320960 TI - Molecular mechanisms of celery seed extract induced apoptosis via s phase cell cycle arrest in the BGC-823 human stomach cancer cell line. AB - BACKGROUND: Mechanisms of apoptosis in tumor cells is an important field of tumor therapy and cancer molecular biology. Loss of cell cycle control, leading to uncontrolled proliferation, is common in cancer. Therefore, the identification of potent and selective cyclin dependent kinase inhibitors is a priority for anti cancer drug discovery. There are at least two major apoptotic pathways, initiated by caspase-8 and caspase-9, respectively, which can activate caspase cascades. Apoptosis triggered by activation of the mitochondrial-dependent caspase pathway represents the main programmed cell death mechanism. This is activated by various intracellular stresses that induce permeabilization of the mitochondrial membrane. Anti-tumor effects of celery seed extract (CSE) and related mechanisms regarding apoptosis were here investigated in human gastric cancer BGC-823 cells. METHODS: CSE was produced by supercritical fluid extraction. Cell viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl-tetrazolium bromide (MTT) assay and apoptosis by flow cytometry using Annexin/PI staining and DAPI staining and a laser scanning confocal microscope (LSCM). Cell cycling was evaluated using PI staining with flow cytometry and expression of cell cycle and apoptosis related proteins cyclin A, CDK2, bcl-2 and bax was assessed by immunohistochemical staining. RESULTS: CSE had an anti-proliferation effect on human gastric cancer BGC-823 cells in a dose- and time-dependent manner. After treatment, the apoptotic rate significantly increased, with morphological changes typical of apoptosis observed with LSCM by DAPI staining. Cell cycle and apoptosis related proteins, such as cyclin A, CDK2 and bcl-2 were all down regulated, whereas bax was up-regulated. CONCLUSIONS: The molecular determinants of inhibition of cell proliferation as well as apoptosis of CSE may be associated with cycle arrest in the S phase. PMID- 22320961 TI - Single nucleotide polymorphisms in the p21 and bcl2 cancer susceptibility genes and breast cancer risk in Saudi Arabia. AB - Certain single nucleotide polymorphisms (SNPs) in genes like p21 or bcl2 increase susceptibility to breast cancer but it has not, until now, been clear whether common polymorphic variants in the same genes also increase risk in Saudi Arabian population. The aim of this study was therefore to determine whether polymorphisms of p21 or Bcl2 might be associated with an increased risk of breast cancer in Saudi women. p21 (rs733590) C/T SNP was not found to be associated with breast cancer pathogenesis. However, we found that a reverse mutation T/C might be linked with breast cancer occurrence. Bcl2 genotypes were marginally associated overall with breast cancer risk. In addition, the alleles of this gene were significantly associated with risk of breast cancer. The allelic frequency of G was higher (0.68) in patients than in healthy women. AA vs. AG+GG genotype [OR=3.56 (1.24-10.68); P=0.008] was the dominant genotype. It is likely that these genes conferring measurably increased risks of breast cancer in our study population. PMID- 22320962 TI - Beginning level nursing students' experiences with cancer patients in their first clinical placement: a qualitative appraisal in Turkey. AB - OBJECTIVE: This study was conducted to evaluate beginning nursing students' point of view related to caring cancer patients in their first clinical placement. METHODS: Data were collected by evaluating the diaries kept by four beginning level nursing students who were assigned to do their fundamentals of nursing clinical practice in hematology clinic from February to May 2011. A qualitative research method was used and data were analyzed using inductive method. FINDINGS: Nursing students experienced anxiety, had difficulties while communicating with cancer patients and observed some negative practices related to patient care and treatment. CONCLUSIONS: During their clinical placement nursing students were able to differentiate right and wrong practices in clinical environment, they tried to tailor their theoretical knowledge to the clinical practice and reported decrease in their anxiety by the end of clinical rotation. Being assigned to care for cancer patients was a stressful experience for the first year students. According to these results, it can be said that clinics such as hematology can be used as a clinical placement only in mandatory conditions for beginning level nursing students because of their limited clinical experience and the knowledge requirement related to these patients. PMID- 22320963 TI - Methylation of secreted frizzled related protein gene in acute leukemia patients in China. AB - BACKGROUND: DNA methylation of CpG islands within the promoters of specific genes may play roles in tumor initiation and progression. It has been suggested such events may serve as critical check points. METHODS: The present study analyzed the methylation status of CpG islands within the promoters of secreted frizzled related proteins (SFRPs) in 87 acute leukemia (AL) patients, 20 normal controls, and four AL cell lines. 5-aza-2'- deoxycytidine (5-Aza-CdR), an inhibitor of DNA methylation, was employed to determine its effect on SFRP expression. RESULT: Methylation of at least one SFRP promoter was observed in 69% of the AL patients analyzed. In addition, methylation of all four SFRP promoters was observed in Molt-4, Jurkat, HL60 and NB4 cells. In Jurkat cells, methylation levels of four SFRP promoters decreased in a dose-dependent manner upon treatment with 5-Aza CdR, which coincided with increased mRNA expression. With increasing 5-Aza-CdR concentrations, the expression of DNA methyltransferases, DNMT3A and DNMT3B, significantly decreased in a dose-dependent manner. CONCLUSION: The present study demonstrated that SFRP gene methylation may be involved in AL progression, with a possible epigenetic mechanism influencing Wnt signaling. PMID- 22320964 TI - Meta-analysis of ALDH2 variants and esophageal cancer in Asians. AB - Alcohol drinking is considered a risk factor for esophageal cancer, and exposure to high levels of acetaldehyde, the principal metabolite of alcohol, may be responsible. Individuals homozygous for the *2 variant allele of aldehyde dehydrogenase 2 (ALDH2) are unable to metabolize acetaldehyde, which prevents them from alcohol drinking, whereas those with *1/*2 have a 6-fold higher blood acetaldehyde concentration postalcohol consumption with respect to *1*1. We carried out a meta-analysis of ALDH2 and esophageal cancer searching for relevant studies on Asians in Medline and EMbase up to May 2011, and investigated the association between this genotype variation and esophageal cancer risk. A total of 2,697 cases and ,6344 controls were retained for the analysis. The pooled OR (95% CI) for ALDH2*1/*2 was 2.47 (95%CI: 1.76-3.46) compared with ALDH2*1/*1. ALDH2*2/*2 showed a non-significant decreased risk for esophageal cancer with OR of 0.6 (0.26-1.38). ALDH2*1/*2 individuals showed a higher risk of esophageal cancer among moderate and heavy alcohol users [2.17(1.95-2.43) and 3.20(2.78 3.70), respectively]. Moderate drinkers with ALDH2*2/*2 showed strong esophageal cancer risk [OR(95%CI)=8.52(3.81-19.04)] compared with ALDH2*1/*1 carriers among heavy drinkers than non-drinkers and moderate drinkers (OR=7.05). Our finding showed that ALDH2*1/*2 genotype increases the risk of esophageal cancer, while the ALDH2*2/*2 genotype reduces the risk, presumably preventing people from consumption due to discomfort. Drinking clearly modifies the effect of ALDH2 on esophageal cancer risk in Asians. PMID- 22320965 TI - A higher number of circulating tumor cells (CTC) in peripheral blood indicates poor prognosis in prostate cancer patients--a meta-analysis. AB - OBJECTIVE: The prevalence of prostate cancer (PCa) is high and PCa is the most common cutaneous cancer in men worldwide. Despite extensive research efforts, very few biomarkers of PCa have been introduced to date in clinical practice. A meta-analysis was performed on the most recently reported CTC to assess its prognostic effect and to elucidate whether its detection in the peripheral blood of patients diagnosed with metastatic, castration-resistant prostate cancer (CPRC) and Hormone Refractory Prostate Cancer (HRPC) can be used as a prognostic factor for survival. METHODS: We searched Science Direct, EMBASE, PubMed, and Cell Research databases for studies that assessed the prognostic relevance of the presence number of circulating tumor cells (CTC) detection in the peripheral blood (PB). A fixed effects model with relative risk (RR) and 95% confidence interval (95% CI) is used for analysis. RESULTS: A total of 4 studies, including 486 patients, were eligible for final analysis. Pooled analysis indicated the presence number of CTC per 7.5 ml peripheral blood is associated with a poor survival rate (RR=2.51, 95% CI 1.96-3.21). CONCLUSION: The unfavorable count (presence of 5 or more CTCs per 7.5 ml peripheral blood) was associated with poor overall survival in patients with PCa. CTC counts can be used as an accurate and independent predictor of survival rate in patients with PCa. PMID- 22320966 TI - Changes in biological and virulent characteristics of Helicobacter pylori exposed to high salt. AB - The effect of high salt environments on biological characteristics of Helicobacter pylori is still unclear. In the present study, we therefore investigated biological characteristics of the bacterium exposed to high salt concentrations. H. pylori strain, L301, was cultured in media supplemented with different concentrations (3%, 15% and 30%) of sodium chloride (NaCl) under microaerophilic conditions for 48 h. Morphology was assessed by light microscopy, the ATP content was quantitated by single-tube fluorescent light-emission and the levels of CagA and UreB proteins were determined by Western blotting. After exposure to NaCl, H. pylori transformed from common spiral shape to U or even coccoid shapes. The ATP content was significantly higher in 30% NaCl group than in 15% and 3% NaCl group and the level of CagA protein increased with the salt concentration. The urease reaction was all strongly positive in H. pylori exposed to different salt concentrations. The level of 8-OHdG expression was significantly increased in GES-1 cells co-cultured with H. pylori exposed to high salt, compared with the level in uninfected cells. H. pylori survives under exposure to high salt concentrations up to 30%, exhibiting changes in mobility, morphology and CagA expression, associated with increased 8-OHdG in the gastric epithelial cells, indicative of DNA damage. PMID- 22320967 TI - Mammography screening uptake among hospital personnel in Kuala Lumpur tertiary hospital. AB - BACKGROUND: Breast cancer is the most common cancer among women in Malaysia. Of the total cancer cases registered in the National Cancer Registry for 2006, 3,525 were female breast cancer cases. The overall age standardized rate was 39.3 per 100,000 population in 2006. An estimated 30%-40% were diagnosed in the late stages and this had resulted in poor survival rates. The purpose of the study was to determine the factors and barriers related to mammography screening uptake among hospital personnel. METHODS: This mixed method explanatory study was carried out on a universal sampling of 707 female personnel aged 40 and above, from June 2007 until November 2007. The study was conducted at University Malaya Medical Centre, a tertiary hospital in Kuala Lumpur. Pre-tested self-administered questionnaires were mailed to eligible personnel. RESULTS: The prevalence of mammography screening uptake was 80.3% (95%CI: 76.8%,83.5%) among 534 respondents. Personnel who had physician recommendation had significantly higher odds of mammography screening uptake compared to those who did not have recommendation, adjusted odds ratio of 21.25 (95%CI:12.71,36.56). Reported barriers can be grouped into several themes; negative perception of the procedure like embarrassment due to the presence of male technicians/radiographers; low confidence with radiologist/radiographers in detecting abnormality; lack of coping skills in dealing with expected results and pain during procedure. CONCLUSIONS: The findings of this study highlighted that 20% of personnel did not undertake mammography screening although there is no cost incurred and the procedure is fully accessible to them. Opportunistic recommendation by physician and concerns on the procedure should be addressed. PMID- 22320968 TI - Prognosis of gingival squamous cell carcinoma diagnosed after invasive procedures. AB - Gingival squamous cell carcinoma (SCC) has a relatively poor prognosis, because differential diagnoses of periodontitis and osteomyelitis are difficult to exclude. As such, gingival SCC is usually diagnosed late, following invasive procedures such as extraction or curettage. The purpose of this study was to classify gingival SCC patients into two groups according to the location of their primary lesion: dentate and edentulous, and to determine the appropriate treatment strategy by comparing clinical and histological features as well as treatment results. The medical records of 76 patients diagnosed with gingival SCC and treated at one institute from 1 January 1993 to 31 December 2007 were reviewed. The overall 5-year survival rate was 60.7%, and the mean survival was 98 months. Factors affecting survival included bone invasion of the primary lesion (p = 0.035), neck node metastasis (p = 0.001), and local recurrence (p = 0.000). The results suggest that more aggressive treatment, such as setting a broad surgical field and enforcing preventive neck dissection, can improve outcome, although they are associated with increased rate of cancer bone invasion and neck metastasis in patients diagnosed with cancer after receiving invasive procedures. PMID- 22320969 TI - Altered expression of miR-21 and PTEN in human laryngeal and hypopharyngeal squamous cell carcinomas. AB - PURPOSE: The purpose of this study was to examine the expression of mir-21 and phosphatase and tensin homologue (PTEN) in laryngeal squamous cell carcinomas (LSCCs) and hypopharyngeal squamous cell carcinomas (HSCCs), and assess correlations between the two as well as with clinical characteristics of patients. METHODS: The expression of mir-21 in tumor and adjacent non-tumor tissues was investigated by real-time RT-PCR. Immunohistochemistry (IHC) was carried out to analyze PTEN protein levels. RESULTS: Mir-21 was up-regulated in LSCCs and HSCCs compared to adjacent non-tumor tissues (P < 0.05), and the up regulated expression of mir-21 was associated with clinical stage (P = 0.001), T classification (P = 0.007), pathologic differentiation (P = 0.025), and lymph node positivity (P = 0.002). In contrast, PTEN IHC staining was notably weaker in tumor tissues than in matched non-tumor tissues (P < 0.05), and the down regulated expression of PTEN was correlated with tumor staging (P = 0.025), the extent of tumor (P = 0.017), and lymph node positivity (P = 0.040). Furthermore, the level of mir-21 was reversely correlated with PTEN expression (P = 0.006). CONCLUSION: mir-21 and PTEN might play important roles in the progression of LSCC and HSCC, the two fcators demonstrating a negative correlation. PMID- 22320970 TI - Feature selection methods for optimizing clinicopathologic input variables in oral cancer prognosis. AB - The incidence of oral cancer is high for those of Indian ethnic origin in Malaysia. Various clinical and pathological data are usually used in oral cancer prognosis. However, due to time, cost and tissue limitations, the number of prognosis variables need to be reduced. In this research, we demonstrated the use of feature selection methods to select a subset of variables that is highly predictive of oral cancer prognosis. The objective is to reduce the number of input variables, thus to identify the key clinicopathologic (input) variables of oral cancer prognosis based on the data collected in the Malaysian scenario. Two feature selection methods, genetic algorithm (wrapper approach) and Pearson's correlation coefficient (filter approach) were implemented and compared with single-input models and a full-input model. The results showed that the reduced models with feature selection method are able to produce more accurate prognosis results than the full-input model and single-input model, with the Pearson's correlation coefficient achieving the most promising results. PMID- 22320971 TI - Comparing visual inspection with acetic acid plus random cervical biopsy plus endocervical curettage to colposcopic directed biopsy plus endocervical curettage in detecting cervical lesions in low-resource settings. AB - OBJECTIVE: To compare the sensitivity, specificity, positive and negative predictive values of visual inspection with acetic acid directed cervical biopsy (VDB) in combination with random cervical biopsy (VRB) and endocervical curettage (ECC) to colposcopic directed biopsy (CDB) plus ECC in detecting cervical lesions (HSIL or more) in Thailand. MATERIALS AND METHODS: A diagnostic-test study was carried out on 164 women with abnormal Pap smear at a tertiary care teaching hospital from March 2011 to June 2011. The women with abnormal Pap smears had further investigations such as; VDB and/or VRB, and CDB plus ECC, and/or loop electrosurgical excision procedure (LEEP). Either VDB plus VRB plus ECC or CDB plus ECC, sometimes LEEP, were used to diagnose cervical lesions. Severest histopathology from any means was taken as the gold standard. RESULTS: There were 164 patients included in analyses. The sensitivity of VDB plus VRB plus ECC to detect cervical lesions was 95.9% (95%CI, 91.4%-98.1%) compared to the sensitivity of CDB plus ECC of 97.3% (95%CI, 93.2%-98.9%). The two were very similar (mean difference -1.4%, 95%CI, -5.4%-2.6%, by Z-test). CONCLUSIONS: Thus VDB plus VRB plus ECC can substitute for CDB plus ECC in detecting cervical lesions in low-resource settings. PMID- 22320972 TI - Impact of body image on quality of life and mood in mastectomized patients and amputees in Turkey. AB - BACKGROUND: The aim was to investigate the impact of loss of the breast on body image, as well as the relationship of the body image with quality of life and severity of the depression, comparing mastectomized patients with those with an apparent limb loss (extremity amputation). METHODS: Demographic data, and the side of the tissue/limb loss for mastectomy and transtibial amputation patients were recorded. Postoperative shoulder range of motion limitations of the operated side in mastectomized patients, and postoperative knee flexion contracture in patients with amputation were evaluated. All patients were asked to complete Body Image Scale, Beck Depression Inventory, and Short Form-36. RESULTS: All of the 40 patients in the mastectomized group were female. In the amputation group, 4 (10.8%) patients were female and 33 (89.2%) were male. Body-image scores in mastectomized and amputation groups were 98.7 +/- 26.5, and 77.2 +/- 19.7, respectively (p<0.05). Physical- function scores of quality-of-life were significantly lower in the amputation group. For both groups, a significant positive relationship was evident between body-image and depression (r=0.327 and r=0.574, respectively). There were also significant negative relationships between body-image and physical role limitations (r=-0.395) and mental health (r= 0.335) in the mastectomized group, and between body-image, and emotional role limitations in the amputation group (p<0.05). CONCLUSIONS: Although mastectomy does not result in loss of physical function, distortion of body image perception is worse than that caused by extremity amputation, and distortion of the body image affects the quality of life and mood negatively in mastectomized patients. PMID- 22320973 TI - Mechanisms of TRAIL and gemcitabine induction of pancreatic cancer cell apoptosis. AB - The aim of this study was to investigate induction of apoptosis by the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and gemcitabine in the pancreatic cancer cell line SW1990. The sensitivity of SW1990 cells to TRAIL and/or gemcitabine-induced apoptosis and the rate of apoptosis were assessed by MTT assay and flow cytometry, respectively. We used Hoechst 33342 staining to observe apoptotic morphology and expression levels of proteins were analyzed by Western blottin. Growth inhibition and apoptosis rates on treatment with the combination of TRAIL and gemcitabine were significantly higher than with each drug alone (p<0.05). Pancreatic cancer cells exhibited a typical apoptosis morphology after treatment with TRAIL or gemcitabine. The levels of cellular apoptosis-associated proteins such as Smac/DIABLO, Cyto C, and the activated fragment of caspase-3 (P17) increased, but the expression of XIAP was significantly decreased after 24 h (p<0.05). SW1990 cells responded to TRAIL and/or gemcitabine-induction of apoptosis in a time and concentration-dependent manner. The mechanism of the apoptosis-sensitization effect appeared associated with significant up-regulation of Smac/DIABLO and cytochrome C, down-regulation of XIAP, and activation of caspase-3. PMID- 22320974 TI - Crocin inhibits proliferation and nucleic acid synthesis and induces apoptosis in the human tongue squamous cell carcinoma cell line Tca8113. AB - BACKGROUND: Cancer chemoprevention is a proven effective strategy for oral squamous cell carcinoma (OSCC). The present study was designed to investigate the effects of crocin, a potential chemopreventive agent, on growth and DNA and RNA content in a human tongue squamous cell carcinoma cell line, Tca8113. METHODS: Tca8113 cells were treated with crocin for 24, 48, 72, and 96 h at concentrations of 0.1, 0.2, 0.4, and 0.8 mM. Tumor cell viability was investigated using the 3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. In addition, Tca8113 cells were treated with 0.4 mM crocin and cytotoxic effects as an inducer of apoptosis were analyzed using flow cytometry. Furthermore, acridine orange (AO) staining and observation using laser scanning confocal microscopy (LSCM) were used to determine the effects of the drug on nucleic acid synthesis. RESULTS: Crocin decreased Tca8113 cell viability and growth remarkably at 24, 48, 72, and 96 h, in a concentration-dependent manner (P<0.05). In addition, 0.4 mM crocin significantly induced both early and late apoptosis of Tca8113 cells. Moreover, the cellular DNA and RNA content was significantly downregulated by 0.4 mM crocin compared with the negative control (P<0.01). CONCLUSIONS: Our observations support the feasibility of applying crocin as a chemoprophylactic agent and treatment for OSCCs. PMID- 22320975 TI - Vascular events in lung cancer. AB - BACKGROUND AND AIMS: In lung cancer, many factors have prognostic significance, including thrombocytosis, which is frequently observed. Associations between vascular events, which are the outcomes of paraneoplastic symptoms, and mortality and morbidity has been evaluated in many studies. The aim of the present study was to evaluate the relationship between thrombocytosis and vascular events. MATERIALS AND METHODS: In total, 281 patients, who were histopathologically diagnosed with lung cancer between March 2007 and August 2009, were evaluated retrospectively. Data analysis was performed using the Statistical Package for the Social Sciences (SPSS) software (ver. 11.5 for Windows). Analysis of the distribution of constant variance for normality was assessed using the Shapiro Wilk test. Nominal variables were evaluated using Pearson's chi-squared or Fisher's exact chi-squared tests. Significant correlations between continuous variables were investigated using Spearman's correlation test. RESULTS: Of the 281 patients, 234 (83.3%) were males and 47 (16.7%) were females, with a median age of 60.6 (31-83 years). Histopathologically, 40 (14.2%) were diagnosed with small-cell lung cancer and 241 (85.8%) with non-small cell lung cancer. In total, 17 (6.04%) vascular events were identified: 11 (64.7%) deep vein thromboses, three (17.6%) pulmonary thromboembolisms, one (5.9%) cerebral arterial thrombosis, and one (5.9%) vena cava superior thrombosis. Thrombocytosis was not determined during thrombosis, but during subsequent visits. CONCLUSIONS: Thrombocytosis is frequently observed in patients with lung cancer. Further prospective studies are required to evaluate the need for prophylactic anticoagulants in these patients. The association between vascular events and survival, the next step of the present study, will be evaluated prospectively. PMID- 22320976 TI - Detection and genotyping of high-risk HPV and evaluation of anti-oxidant status in cervical carcinoma patients in Tamil Nadu State, India--a case control study. AB - Cervical cancer is the second common type of cancer among women worldwide, with the human papillomavirus (HPV) recognized as the major causative agent. The HPV 16/18 prevalance in cervical cancer patients from the Trichy and Coimbatore districts of Tamil Nadu state, India, was evaluated in addition to an assessment of oxidative stress and antioxidant status. MDA, GSH, GPx, GST, SOD, vitamin C and vitamin E were estimated in the plasma and erythrocytes of the twenty patients and an equal number of age matched normal subjects as controls. 119 paraffin embedded tissue samples were collected to perform DNA extraction and genotyping of HPV 16/18 using specific primers. Plasma and erythrocyte TBARS level was significantly elevated in the cervical cancer patients compared to normal. It was observed that SOD, GPx, GSH levels in the erythrocyte and plasma was significantly lower in cervical cancer patients, as well as GST and Vitamins E and C levels in the plasma and catalase enzyme levels in the erythrocytes. Genotyping showed 57% positive for HPV16 and 18% for HPV18, indicating that vaccination against these two will effectively reduce the burden associated with the disease. These findings suggest possible use of antioxidant supplementation as prophylactic agents for prevention and treatment of cervical cancer. PMID- 22320977 TI - Protective effects of silymarin against doxorubicin-induced toxicity. AB - OBJECTIVES: The aim of the present study was to investigate the effect of silymarin on doxorubicin-induced toxicity to the rat kidney, heart, and liver. MATERIALS AND METHODS: A single dose of 10 mg/kg doxorubicin was injected intraperitoneally (ip) in the doxorubicin group. The silymarin group received silymarin (100mg/kg) every other day. In the doxorubicin + silymarin group, silymarin was injected ip at 100 mg/kg dose for 5 days before doxorubicin administration (10 mg/kg, single ip injection) and then continued daily thereafter until euthanization. On the seventh day after doxorubicin injection, eight animals from each group were decapitated and liver and heart samples were obtained. The remaining eight animals of each group continued to receive silymarin every other day, till euthanized on the twenty first day. Serum was separated for determination of superoxide dismutase (SOD), glutathione peroxidase (GSHPx), catalase (CAT), malondialdehyde (MDA), nitric oxide (NO), creatinine, urea, AST, ALT, lactate dehydrogenase (LDH) and creatinine phosphokinase (CPK) activities. Histopathological and electron microscopic examinations of heart, kidney and liver sections were also performed. RESULTS: Doxorubicin caused a significant increase in serum NO levels compared to controls. Silymarin pretreatment group lowered these. Histopathological and electron microscopic examinations of kidney, heart, and liver sections showed doxorubicin to cause myocardial and renal injury which was levv evident in silymarin treated rats. CONCLUSION(S): Results of the present study indicate that silymarin significantly protected doxorubicin-induced toxicities to the rat kidney, heart, and liver, thus suggesting its administration as a supportive care agent during anti-cancer treatment featuring doxorubicin. PMID- 22320978 TI - Endostar combined with chemotherapy versus chemotherapy alone for advanced NSCLCs: a meta-analysis. AB - To evaluate the clinical efficacy and safety of rh-endostatin (Endostar) combined with chemotherapy in the treatment of patients with non-small cell lung cancer (NSCLC), we selected data from the Cochrane Library, EMBASE, Medline, SCI, CBM, CNKI, etc to obtain all clinical controlled trials, including the addition of endostar to chemotherapy in advanced NSCLC patients. The quality of included trials was evaluated by two reviewers independently. The software RevMan 5.0 was provided by Cochrane Collaboration and used for meta-analyses. Fifteen trials with 1335 patients were included according to the including criterion. All trials were randomized controlled trials, and two trials were adequate in reporting randomization. Thirteen trials didn't mention the blinding methods. Meta-analysis indicated that the NPE arm (Vinorelbine+ cisplatin+Endostar) had a different response rate compared with NP(Vinorelbine+ cisplatin) arm (OR2.16, 95%CI 1.57 to 2.99). The incidences of severe Leukopenia (OR0.94, 95%CI 0.66 to 1.32) and severe thrombocytopenia (OR 1.00, 95%CI 0.64 to 1.57) and Nausea and vomiting (OR 0.85, 95%CI 0.61 to 1.20) were similar in the NPE arm compared with those in the NP arm. The NPE plus radiotherapy(RT) arm had a similar response rate compared with NP plus RT arm (OR 2.39, 95%CI 0.99 to 5.79). The incidences of Leukopenia (OR0.83, 95%CI 0.35 to 1.94) and thrombocytopenia (OR 0.78, 95%CI 0.19 to 3.16) and radiation esophagitis (OR 1.00, 95%CI 0.40 to 2.49)were similar in the NPE plus RT arm compared with those in the NP plus RT arm. Our results suggest that in the treatment of advanced NSCLCs, Endostar in combination with platinum-based chemotherapy can improve the response rate without obviously increasing side effects. PMID- 22320979 TI - The antitumor activity of exogenous and endogenous canstatin on colorectal cancer cells. AB - Colorectal cancer is the third most common malignancy and the third-leading cause of cancer-related deaths worldwide. In the last several years, recombinant DNA technology has made cancer gene therapy feasible in the clinic. In our studies, we used both exogenous and endogenous canstatin, a type IV collagen genetically distinct product. We detected the effects of canstatin on colorectal cancer cells HCT-15 and HCT-116. DAPI staining, FCM and migration analyse were used to detect the apoptotic cells, cell cycle and mobility. As shown in the results, the apoptotic cell numbers (p<0.05) and G1 arrest cell numbers (p<0.05) were higher than in the non- treatment case. The mobility of the cells was also decreased obviously (p<0.05). Simultaneously, combination effects of exogenous and endogenous canstatin were identified. PMID- 22320980 TI - Inhibition of proliferation, viability, migration and invasion of gastric cancer cells by Aurora-A deletion. AB - Accumulating evidence has demonstrated Aurora-A to be frequently overexpressed in many cancers, including gastric cancer. In order to study the effects of Aurora-A on gastric cancer cells, we detected the changes of cell phenotype after treatment with Aurora-A specific small interference RNA (siRNA). In addition, VX 680 was used simultaneously. RT-PCR and western-blot were used to determine the level of Aurora-A mRNA and protein in cells, including GES-1, SGC-7901, SGC-7901 lines treated with VX-680, SGC-7901 treated with DMSO, SGC- 7901 interfered using siRNA and SGC-7901 interfered using scrambled RNAi. MTT, PI staining and transwell assays were used respectively to analyze proliferation, viability, and migration and invasion of the cells. The results showed that deletion of Aurora-A may inhibit proliferation and induce G1 arrest. The transwell assay indicated that Aurora-A may promote metastasis of gastric cancer. Collectively, our findings support Aurora-A as an oncogene in gastric cancer. Deletion of Aurora-A may have potential as a therapeutic method for gastric cancer. PMID- 22320981 TI - Antitumor activity of NF-kB decoy oligodeoxynucleotides in a prostate cancer cell line. AB - BACKGROUND: Nuclear factor-kappaB (NF-kB), a transcription factor, is abundantly expressed in prostate cancer and regulates many tumor-related genes. Given the important roles of these genes in tumor control, the present study was conducted to test the hypothesis that there was different expression of NF-kB in androgen- dependent or androgen-independent prostate cancer cells. In addition NF-kB decoy oligodeoxynucleotides (ODNs) were transfected into two prostate cancer cells to determine affects on growth and apoptosis. METHODS: First, NF-kB decoy ODNs were designed according to the NF-kappaB elements in the promoter region of c-myc gene. Then, NF-kB and control decoy ODNs were transfected with lipofectamine. Their influence on prostate cancer cell line proliferative activity was detected by MTT assay. Cell apoptosis was determined by flow cytometric(FCM) analysis and AO/EB study. Thirdly, nuclear extracts were prepared from PC-3M cells and DNA protein interactions were examined by electrophoretic mobility shift assay (EMSA). Lastly, to confirm mechanisms of action, a pGL3-C-MYC luciferase expression vector containing a fragment of the c-myc promoter was constructed and co-transfected with NF-kB decoy ODNs into PC-3M cells with lipofectamineTM2000. Expression levels of related endogenous genes were assessed by western blotting. RESULTS: We found overexpression of NF-kB in the androgen-independent prostate cancer cell line PC-3M compared to the androgen-independent LNCaP. Treatment with NF-kB decoy ODNs resulted in strong suppression of proliferation, especially in the PC-3M case. Induction of apoptosis of PC-3M was observed in FCM and AO/EB studies. Activity of luciferase was significantly reduced in the NF-kB decoy transfected cells, but not in cells transfected with a control decoy. Furthermore, we found that expression of some endogenous genes was reduced, while other genes transcripts were induced. EMSA demonstrated specific binding of the NF-kB decoy to NF-kB protein. CONCLUSIONS: These findings indicate that NF-kB activation plays an important role in evolution of androgen-independent prostate cancer via manipulating expression of target genes. Inhibitors of NF-kB may thus offer promise as a therapeutic approach for the treatment of androgen-independent prostate cancer. NF-kB decoy ODNs may allow development of therapeutic and investigative tools for human malignancies. PMID- 22320982 TI - Clinicopathological features and survival of testicular tumours in a Southeast Asian university hospital: a ten-year review. AB - INTRODUCTION: Testicular cancer mainly affects young men worldwide. There is lack of published data on patients with this malignant condition from the Southeast Asian region. The aim of this study was therefore to determine the clinicopathologic features of testicular cancer patients treated in a Southeast Asian university hospital and their overall survival rate. MATERIALS AND METHODS: This was a retrospective study of testicular cancer patients treated between January 2001 and February 2011. Their epidemiological data, clinical presentation, pathologic diagnosis, stage of disease and treatment were gathered and the overall survival rate of this cohort was analyzed. RESULTS: Thirty-one patients were included in this study. The majority of them were of Malay ethnicity. The average age at presentation was 33.7 years. The commonest testicular cancer was non-seminomatous germ cell tumour, followed by seminoma, lymphoma and rhabdomyosarcoma. More than half of all testicular germ cell tumour (GCT) patients had some form of metastasis at diagnosis. All the patients were treated with radical orchidectomy. Adjuvant chemotherapy was given to those with metastatic disease. Four seminoma patients received radiotherapy to the para aortic lymph nodes. The 5-year survival rate for all testicular cancers in this cohort was 83.9%. The survival rate was 88.9% in 5 years when GCT were analyzed separately. CONCLUSION: GCT affects patients in their third and fourth decades of life while lymphoma patients are generally older. Most of the patients treated for GCT are of Malay ethnicity. The majority have late presentation for treatment. The survival rate of GCT patients treated here is comparable to other published series in other parts of the world. PMID- 22320983 TI - Promoter methylation and genetic polymorphism of glutathione S-transferase P1 gene (GSTP1) in Thai breast- cancer patients. AB - The GSTP1 gene encodes for a detoxification enzyme involved in protecting cells from carcinogens. In breast cancer, GSTP1 polymorphisms may produce lower effective enzyme detoxification properties and GSTP1 promoter hypermethylation may result in inactivation of GSTP1 expression. We therefore hypothesized an influence on progression of breast cancer. To study the effect of GSTP1 polymorphisms and CpG-island hypermethylation on GSTP1 promoter, PCR-RFLP and methylation-specific PCR techniques were used with 41 Thai breast-cancer patients. Associations between the codon 105 (A to G) genetic polymorphism, CpG island hypermethylation, and clinico-pathological parameters were analyzed. GSTP1 hypermethylation was found in 26% of cases and the GSTP1 polymorphism in 14%. GSTP1 hypermethylation was significantly associated with breast cancer; lymph node metastasis (P = 0.02) while GSTP1 polymorphism status significantly varied with progesterone receptor positivity (P = 0.04). No association was found between the GSTP1 polymorphism and methylation status. The results indicated that CpG-island hypermethylation of the GSTP1 promoter is associated with a biologically aggressive phenotype, but may not be related to the codon 105 (A to G) gene polymorphism in breast-cancer patients. PMID- 22320984 TI - The impact of mammographic breast cancer screening in Singapore: a comparison between screen-detected and symptomatic women. AB - BACKGROUND: Breast cancer is the leading cause of cancer death amongst Singapore women. There are few studies evaluating the impact of mammographic screening among Asian women. This study aimed to examine differences in disease stage at presentation and outcome between breast cancer patients who were detected by screening (screen-detected) and those who presented symptomatically (symptomatic) from the experience of a regional hospital in Singapore. We also sought to identify the demographic profile of patients who were less likely to be screen detected. METHODS: Retrospective data for female patients diagnosed with primary breast cancer and treated from January 2002 - December 2008 were analyzed. Univariate and multivariate analyses were performed to examine the profile of symptomatic as opposed to screen-detected patients and factors that influence presentation at an early disease stage. Survival and recurrence rates were computed by Kaplan-Meier method and compared by log rank test. RESULTS: The study population consisted of 82 screen-detected and 679 symptomatic patients. The screen-detected patients were more likely to present at an earlier stage and have better overall cancer-specific survival as compared to symptomatic patients. Malay women and those without a family history of breast cancer were less likely to be detected by screening. CONCLUSIONS: Mammographic screening appeared to enable the detection of oncologically more favorable lesions and conferred better overall cancer- specific survival in Singapore women. There is possibly room for more targeted education efforts to reach out to Malay women and those without a family history of breast cancer to enable earlier disease detection among these individuals through regular breast cancer screening. PMID- 22320985 TI - Loss of heterozygosity at 6p21 and HLA class I expression in esophageal squamous cell carcinomas in China. AB - BACKGROUND AND OBJECTIVE: The loss or downregulation of human leukocyte antigen ( HLA-I) has been proposed to contribute to immune evasion by cancer cells. Since the human leukocyte antigen (HLA-I) complex is located at 6p21.3, loss of heterozygosity of this region may alter HLA class I tumor phenotypes. The aim of this study was to analysis loss of heterozygosity (LOH) of chromosome 6p in ESCC samples and correlate this with HLA class I expression. MATERIALS AND METHODS: A total of 87 formalin-fixed, paraffin-embeded and frozen-fresh of ECSS lesions were collected. HLA-Iand antigen-processing machinery component expression was investigated by immunohistochemistry with anti-HLA class I monoclonal antibody and a panel of 49 ESCCs with downregulated HLA class I expression were selected for LOH studies using 3 microsatellite markers located at 6p21.3 (D6S105,D6S265,D6S273). RESULTS: HLA-Iantigen,TAP1 and LMP were lost or down regulated in 57.5, 29.8 and 47.0% of the ESCC lesions, respectively. In 23/49(46.9%) of the ESCCs, allelic loss for at least one locus at 6p21.3 was found. CONCLUSIONS: Our data show that downregulation of HLA class I expression is correlated with loss of heterozygosity regions at 6p21.3 in ESCC. PMID- 22320986 TI - Interaction between CYP19A1 polymorphisms and body mass index in the risk of endometrial cancer in postmenopausal Japanese women. AB - Extra-ovarian sex hormone production plays an important role in endometrial cancer in postmenopausal women. Aromatase, which is encoded by CYP19A1, is a key enzyme in estrogen biosynthesis after menopause. To examine the association between polymorphisms in CYP19A1 and endometrial cancer risk among postmenopausal Japanese women, we conducted a hospital-based case control study in 48 patients with histologically diagnosed incident endometrial cancer and 253 non-cancer control subjects. Information on lifestyle factors was obtained from a self administered questionnaire. Twenty-five tag SNPs (single nucleotide polymorphisms) of CYP19A1 were examined by TaqMan methods and haplotype blocks were identified by LD analysis. Associations were assessed by an unconditional logistic regression model adjusted for potential confounders. We found no significant association between CYP19A1 genotypes and haplotypes and endometrial cancer risk. However, among women with a BMI (body mass index) >23, significantly positive associations were observed for rs2899473, rs1865803, rs16964220, rs2008691, rs17647707, rs17647719, rs1902586, rs936306, and rs1004982, while negative associations were seen for rs1902585, rs752760 and rs2445768. These showed significant interactions with BMI. Further, of the six haplotype blocks identified, the haplotype CTT of block 1, GATA of block 5 and CA of block 6 showed statistically significant interactions with BMI. These results suggest that CYP19A1 polymorphisms might play an important role in the etiology of endometrial cancer, and that the effect of these polymorphisms might be influenced by BMI. PMID- 22320987 TI - Association and correlation of different chemotherapeutic regimens and doses with onset and severity of anemia among solid cancer patients. AB - INTRODUCTION: Anemia is considered as one of the most frequent hematological demonstration of malignant diseases, which lead to momentous impairment in every tissues and organs of cancer patients and put them under serious stress. This major problem may arise because of the underlining diseases (i.e., cancer diseases) or radiotherapy or chemotherapy treatment received. This present study tries to find the association between anemia onset and severity with different chemotherapeutics regimens used in the treatment of several solid cancers and to find the association of anemia onset and severity with different doses of these chemotherapeutics drugs. METHODS: This retrospective observational study was conducted in Penang General Hospital on 534 anemic solid cancer patients who were admitted between 2003 and 2009. The main statistical tests used were Chi-square test and Logistic regression test for categorical data. While for continues data the main statistical tests were Linear regression and correlation test. The significance of the result will be when the P<0.05, while the confidence interval for this study was 95%. RESULTS: FEC, 5-FU+5-FU, Docetaxel and Cisplatin+ 5-FU regimen has strong association and correlation with anemia onset and severity. However the associations and correlations with anemia severity were stronger than those with the onset. Different doses of 5-FU, cyclophosphamide, docetaxel and cisplatin play a critical role in anemia onset and severity. CONCLUSION: Monitoring and determination of hemoglobin levels for cancer patients treated with FEC, 5-FU+5-FU, Docetaxel, Cisplatin+ 5-FU specifically with high doses must be emphasized and a focus of particular attention. PMID- 22320988 TI - Lansoprazole induces collagenous colitis in the colon of Mongolian gerbils. AB - Collagenous colitis (CC) is an illness characterized by chronic diarrhea with possible effects on neoplastic development, but there have been no reports in animals. We therefore tried to establish CC development in a Mongolian gerbil (MG) model by long-term continuous lansoprazole (LPZ) administration and aimed to clarify the relationship between LPZ administration and CC occurrence. We divided 69 gerbils into 6 groups: Helicobacter pylori (Hp)-infected+high-dose LPZ, Hp infected+low-dose-LPZ, Hp-infected, high-dose-LPZ, low- dose-LPZ, and control. The gerbils were sacrificed and entire colons were excised at experimental weeks 27, 54, and 108. We examined colonic lesions by staining of Swiss-roll intestines pathologically. A total of 3 gerbils had CC-like lesions in the proximal colon. All MGs with CC-like lesions were from LPZ treated groups (3 of 35; 8.6%). The thickened subepithelial collagen band detected in these lesions strongly resembled that of human CC lesions. Immunohistochemical analysis indicated a tendency for more chromogranin A-positive cells in the upper layer of colonic crypt following continuous LPZ administration. In conclusion, we successfully established development of CC-like lesions in an MG model by continuous LPZ administration and determined that the ectopic endocrine cells that were induced by LPZ administration may influence the occurrence of these lesions in the colon. PMID- 22320989 TI - Mortality of oral cavity cancer in Iran. AB - BACKGROUND: Oral cavity cancer is the eighth most frequent cancer among men in the world. Its incidence varies widely geographically and two-thirds of the incident cases are diagnosed in developing countries. The aim of this study was to present the mortality trends from this cancer for Iranian population during a period of almost a decade, in order to provide update information regarding time trends for this cancer. METHODS: We analyzed National death Statistics reported by the Iranian Ministry of Health and Medical Education from 1995 to 2004, stratified by age group, sex, and cause of death. Oral cavity cancer [ICD-10; C00 08] was assessed for annual mortality rates/100,000, overall, by sex and by age group (<15, 15-49 and >= 50 years of age) and age standardized rates (ASR) were calculated. RESULTS: The age standardized mortality rate of oral cavity cancer increased dramatically during these years from 0.09 per 100,000 in 1995 to 0.59 per 100,000 in 2002. However, a sharp decrease was observed from 2002 to 2004. Moreover the mortality of oral cavity cancer was higher for males except from 2000-2002 during which the rate of female's death was close to male's. Age specific rates for oral cavity cancer indicated higher mortality rate for older age. CONCLUSION: In conclusion, this study provides comprehensive projection for burden of death due to oral cavity cancer, indicating that the trend of its mortality was increased in recent decade and then would be leveled off. While the burden of oral cavity cancer in Iran is lower than other Asian countries, further studies are required to establish risk factors or modifiers for this cancer in Iranian population in order to decrease its incidence and mortality. PMID- 22320990 TI - Lack of germ line changes in KISS1 and KAI1 genes in sporadic head and neck cancer patients of Pakistani origin. AB - BACKGROUND: Head and neck cancer is included among the top five most commonly prevailing cancers worldwide. Abnormalities of either genetic or epigenetic factors are found responsible for the development and progression of head and neck cancer. Metastasis is the leading cause of death in patients with head and neck cancer. Down regulation of metastasis suppressor genes (MSGs) expression have been frequently observed in advanced tumours. METHODOLOGY: The present study was designed to screen two of the most frequently down-regulated MSGs (KISS1 and KAI1) for mutations in 120 diagnosed head and neck cancer affected Pakistani patients. The questionnaire was filled for basic information about age, gender, smoking habits and area of cancer affected and other relevant details. Primers for both genes were designed using "Primer 3" software in such a way that both intron exon boundaries were included in this region. DNA isolation and estimation was done by using organic method and agarose gel electrophoresis. Single Strand conformational polymorphism technique was used after amplification of the respective genes. Mobility patterns were analyzed using BioDoc Analyzer. RESULTS: Data of patients were analyzed on the basis of age, sex and type of cancer as variables. The mean age of patients and controls was 44 years. There were 53% females and 47% males in this group of study, 63% nonsmokers and 37% smokers and larynx cancer was found to be most frequent type of cancer with a percentage of 64. Lack of germ line mutation was observed in the entire coding region in both coding regions as well as splice sites of the respective genes. CONCLUSION: Germ line mutations in KISS1 and KAI1 are thus considered to be a less frequent event in head and neck cancer patients. However, two polymorphisms in intronic region of exon 3 and exon 9 of KAI1 gene were observed in 1% of patients. In non coding region downstream of exon 3 (KAI1), there was a C 29166 T substitution and in intronic region upstream exon 9 of KAI1 gene, a C 52840 A substitution was observed. Both patients were females with ages 47 and 50 years respectively. A detailed analysis of regulatory mechanism is required to explore the genetic basis of down regulation of these MSGs for a better understanding of head and neck cancer progression. PMID- 22320991 TI - Genetic changes in the PTEN gene and their association with breast cancer in Pakistan. AB - The PTEN gene, a candidate tumor suppressor, is one of the more commonly inactivated and extensively studied genes in cancer. However, few data are available about the role of germ line mutations of this gene in sporadic breast cancer cases. The purpose of this study was to determine extent of involvement of this gene in breast cancer in Pakistan. To test the hypothesis that genetic variations of PTEN play a role in the etiology of breast cancer, a population based case-control study was conducted in 350 breast cancer patients along 400 healthy controls. After extracting DNA from blood, the whole coding sequence of PTEN along with intron/exon boundaries was genotyped by polymerase chain reaction single stranded conformational polymorphism. Sequencing analysis revealed nineteen different types of mutations in different regions of PTEN (in exon 2, 4, 5, 6, 7 and splicing sites of intron 2 and 4 and also in the 3' UTR region), including 3 silent, 8 missense, 2 frame shift and 6 splice site variations. Among the observed variations in this study, three missense mutations have already been reported i.e. 319G>A (Asp106Asn), 389G>A (Arg129Gln) and 482G>A (Arg160Lys) in different populations. The present results suggest that a wide range of germline PTEN mutations may play a role in the pathogenesis of breast cancer. PMID- 22320992 TI - OGG1 gene sequence variation in head and neck cancer patients in Pakistan. AB - In Pakistani culture tobacco use is very high and a well known risk factor for developing head and neck cancer (HNC), tobacco smoke containing high quantities of chemical carcinogens such as aromatic amines and reactive oxygen species. OGG1 is the primary enzyme in the base excision repair (BER) pathway, responsible for the excision of 7, 8-dihydro-8-oxoguanine, a mutagenic base byproduct that occurs as a result of exposure to reactive oxygen species. Groups of 300 already diagnosed HNC patients along with normal controls were included in this study. PCR-single-strand conformation polymorphism and DNA sequencing were used to analyze the whole coding region of OGG1 gene. Sequence analysis revealed eight novel mutations (six missense and two frame shift mutations). Frequencies of missense mutations, Asp267Asn, Ser279Gly and Ile253Phe were 0.12, 0.13 and 0.06 respectively. Frequencies of other missense mutations, 1578A> T, 1582C> T and Ala399Glu (1542C> A) were 0.13, 0.13 and 0.16, whereas values for the frame shift mutations 1582insG and 1543-1544delCT were 0.13 and 0.16. In our study, incidence of these mutations was found higher in oral cancers (p<0.002) and in smokers (p<0.002) when compared with other sites of HNC and nonsmokers, respectively. Our finding suggests that these germline mutations in OGG1 gene contribute to risk of developing HNC. PMID- 22320993 TI - Expressional alterations and transcript isoforms of metastasis suppressor genes (KAI1 and KiSS1) in breast cancer patients. AB - BACKGROUND: Metastasis suppressor genes are involved in the inhibition of a cancer cell's ability to metastasize. Down expression of such genes may contribute to pathogenesis of breast cancer. The aim of current study was firstly to evaluate expression of two examples, KAI1 and KISS1, and then to determine relationships with stages of breast cancer in a Pakistani population. METHODOLOGY: Fresh biopsy tissues were collected from different hospitals and oncology research institutes. The semi quantitative reverse transcriptase polymerase chain reaction was used to investigate KAI1 and KISS1 expression in 25 breast tumor tissues and 25 normal tissues. Statistical analysis was performed to explore its association with breast cancer risk. RESULTS: The present study revealed that KAI1 and KISS1 mRNA expression was markedly reduced in tissues of breast cancer compared to adjacent normal tissue. In present study a splice variant of KAI1 during a screen for its expression analysis was also observed. This splice variant has not been reported previously. CONCLUSIONS: Metastasis suppressor genes demonstrate reduced expression in breast cancers in Pakistan. PMID- 22320994 TI - Biliary brush cytology in the assessment of biliary strictures at a tertiary center in Iran. AB - BACKGROUND: Confirmation of cholangiocarcinoma and other malignant bile duct stenosis is challenging. The aim of the current study was to assess the accuracy of brush cytology for diagnosis of malignant biliary strictures. METHODS: 105 patients with hepatic biliary strictures undergoing ERCP were included in this study. Prospectively collected data included symptoms, results of biochemical testing and imaging procedures, as well as details of ERCP. Exclusion criteria were: 1) strictures that would not permit passage of guidewire and brush accession; and 2) post-operative strictures. Brushings of the bile duct strictures were performed. All patients were followed for at least 6 months. The final diagnosis was confirmed following surgery, histopathological diagnosis of the lesion, radiological infiltration of adjacent organs or metastases, or after at least a 6-month follow-up. RESULTS: 88 brush samples from 88 patients were of appropriate quality. The overall diagnostic sensitivity and specificity for malignant nature of biliary strictures were 40.7% and 100%, respectively. The sensitivity was 66.6 % for ampullary carcinomas, 36.3% for pancreatic cancer and 32.5% for cholangiocarcinomas. CONCLUSIONS: Despite the low sensitivity, due to the relative ease and safety, brush cytology should remain the first choice for diagnosis of causes of biliary strictures. PMID- 22320995 TI - Weekly TP regimen as a postoperative adjuvant chemotherapy for completely resected breast cancer in China: final result of a phase II trial. AB - OBJECTIVES: To investigate the safety and long-term survival with weekly paclitaxel combined with cisplatin (wTP) as a postoperative adjuvant chemotherapy regimen for breast cancer. METHODS: Patients with breast cancer were treated postoperatively with paclitaxel 40 mg/m2 intravenously on days 1, 8 and 15, cisplatin 25 mg/ m2 also intravenously on days 1,8 and 15, repeated every 21-28 days as a cycle. Toxicity and survival rate were evaluated after chemotherapy. RESULTS: Between September 1993 and August 2001, 20 patients were enrolled. Median age was 52 years (range, 35-71 years). According to the TNM stage system, all patients were staged II or III. Median number of chemotherapy cycles was 3 (range, 1-6), and 10 patients received 4 to 6 cycles of wTP. After a median follow-up of 83 months, 2 deaths and 6 relapses were documented. The five year overall survival rate was 90%. All patients could be evaluated with regard to toxicity. No treatment related deaths were recorded. Neutropenia occurred in 75% of patients during treatment, all recovering after G-CSF injection. Other symptoms included nausea/vomiting, elevation of transaminase, urea nitrogen/creatinine and alopecia. CONCLUSIONS: wTP is safe and effective at the doses tested. However, a randomized clinical trial is needed to compare wTP with other conventional adjuvant regimens of breast cancer postoperatively. PMID- 22320996 TI - Insufficient screening knowledge in Chinese interns: a survey in ten leading medical schools. AB - OBJECTIVE: This study aimed to investigate Chinese medical interns' cancer knowledge and associated factors, focusing on cancer screening. METHODS: A questionnaire survey was conducted in ten leading Chinese medical schools from June to July in 2011. Medical interns were invited to fill the questionnaire. RESULTS: Out of the 1350 copies sent, 1135 eligible responses were returned. Around 50% of interns had positive attitude toward oncology, but the knowledge score was low, particularly in screening. The percentages of scores were 44.8% (8.95/20) for overall and only 29.6% (2.07/7) for screening. The majority of internship length in oncology department was eight to fourteen days. Screening and prevention was ranked as third most taught, following diagnosis and treatment. Multivariate analysis showed that positive attitude to oncology correlated with positive self-evaluated overall (OR = 1.76, 95% CI (1.45, 2.12)) and screening (OR = 1.62, 95% CI (1.35, 1.95)) competence, but unexpectedly predicted lower screening score (OR = 0.77, 95% CI (0.61, 0.97)). Interns with positive self-evaluated screening competence were not found to possess higher cancer screening knowledge. CONCLUSION: Current medical education in Chinese medical schools fails to equip interns with optimal cancer knowledge, particularly in screening, even in interns who hold positive view to oncology. Interns' self-evaluated competence is not proportional to their knowledge scores. PMID- 22320997 TI - Never smokers with lung cancer: analysis of genetic variants. AB - It is well-known that tobacco smoke is a definite causative agent important for human health. Epidemiological research has proven that smoking is a cause of various serious and fatal diseases. However, never-smokers comprise a high proportion of non-small-cell lung cancer (NSCLC) patients. To determine whether lung cancer patients in never smokers have different genetic mutations from their counterparts in smokers, we comprehensively searched the Cochrane Library, Medline and EMbase from 1966 to Jun 2010 for the following terms: ("non- smoker" or "never-smoker") and ("lung cancer") and ("gene") limited to English and clinical trials. Although a significant fraction of lung cancers in never smokers may also be attributable to tobacco, many such cancers arise in the absence of detectable tobacco exposure, and may follow a very different molecular pathway of malignant formation, including EGFR gene mutation, P53 mutation and metabolic gene CYP1AIIle462Val polymorphism. These genes will help doctors to separate never-smoker lung cancer from smokers, and may present promising targets for therapy of never-smoker lung cancers. Future efforts should focus on further delineation of underlying biologic differences, identifying potential non-tobacco related risk factors, and refining treatment strategies for different groups of lung cancer patients. PMID- 22320998 TI - Distinctive characteristics of bronchial reticular basement membrane and vessel remodelling in chronic obstructive pulmonary disease (COPD) and in asthma: they are not the same disease. AB - AIMS: This study compared reticular basement membrane (Rbm) and vascular remodelling within the bronchial mucosa of subjects with chronic obstructive pulmonary disease (COPD) with those from patients with asthma, to test the 'Dutch hypothesis' of whether these are essentially the same or different pathological conditions. METHODS AND RESULTS: Bronchoscopic biopsies were stained with anti collagen IV antibody; 18 current smoking COPD, 10 symptomatic asthmatics and 13 healthy non-smoking controls were studied. The Rbm in COPD was fragmented, non homogeneous, variable in thickness and hypervascular, whereas in asthma the Rbm was compact and homogeneous with no evidence of increased vascularity compared to controls. Length of Rbm splitting presented as percentage of Rbm length was used to measure fragmentation; it was greater in COPD than in controls and asthmatics [median (range) 20.7% (0.4-68.5) versus 5.3% (0.0-21.7) versus 1.5% (0.0-15.1), P < 0.001]. The number of Rbm vessels/mm Rbm [median (range) 10.1 (1.6-23.0) versus 4.5 (0.0-26.4) versus 4.4 (0.4-8.1), P < 0.01] and area of Rbm vessels, MUm(2) /mm Rbm [median (range) 953 (115-2456) versus 462 (0-3263) versus 426 (32-2216), P < 0.05] was also increased in COPD compared to normal subjects and asthmatics. CONCLUSIONS: The characteristics of Rbm remodelling are quite different in asthma and COPD. PMID- 22320999 TI - Clinical and genetic outcome determinants of Internet- and group-based cognitive behavior therapy for social anxiety disorder. AB - OBJECTIVE: No study has investigated clinical or genetic predictors and moderators of Internet-based cognitive behavior therapy (ICBT) compared with cognitive behavioral group therapy for (CBGT) for SAD. Identification of predictors and moderators is essential to the clinician in deciding which treatment to recommend for whom. We aimed to identify clinical and genetic (5 HTTLPR, COMTval158met, and BDNFval66met) predictors and moderators of ICBT and CBGT. METHOD: We performed three types of analyses on data from a sample comprising participants (N = 126) who had undergone ICBT or CBGT in a randomized controlled trial. Outcomes were i) end state symptom severity, ii) SAD diagnosis, and iii) clinically significant improvement. RESULTS: The most stable predictors of better treatment response were working full time, having children, less depressive symptoms, higher expectancy of treatment effectiveness, and adhering to treatment. None of the tested gene polymorphisms were associated with treatment outcome. Comorbid general anxiety and depression were moderators meaning that lower levels were associated with a better treatment response in ICBT but not in CBGT. CONCLUSION: We conclude that demographic factors, symptom burden, adherence, and expectations may play an important role as predictors of treatment outcome. The investigated gene polymorphisms do not appear to make a difference. PMID- 22321000 TI - Do men with prostate abnormalities (prostatitis/benign prostatic hyperplasia/prostate cancer) develop immunity to spermatozoa or seminal plasma? AB - Prostate is an immunocompetent and not an immunoprivileged organ. It has an active immunologic armamentarium. There are three major prostate abnormalities namely, prostatitis, benign prostatic hyperplasia (BPH) and prostate cancer. In all these abnormalities, infection/inflammation has been implicated. As infection/inflammation of the male genital tract can also be involved in induction of antisperm antibodies (ASA), this study was conducted to examine if these prostate abnormalities lead to the formation of ASA. Sera were obtained from normal healthy men (n = 20), men with chronic prostatitis (n = 20), men with BPH (n = 25), men with prostate cancer (n = 25) and immunoinfertile men (n = 10). The presence of antisperm antibodies against lithium diiodosalicylate (LIS) solubilized human sperm extract (HSE), seminal plasma and synthetic peptides based upon sperm-specific antigens namely fertilization antigen (FA-1) and YLP(12), were analysed using the sperm immobilization technique (SIT), tray agglutination technique (TAT), enzyme-linked immunosorbent assay (ELISA) and indirect immunobead binding technique (IBT). All the sera from normal men and men with prostate abnormalities (chronic prostatitis/BPH/prostate cancer) were found to be negative in SIT and TAT. In ELISA, a few sera from men having prostate abnormalities (4-24%) showed a weak positive immunoreactivity (2-3 SD units) with some of the spermatozoa/seminal plasma antigens. Majority of the samples did not show any immunoreactivity (<2 SD units) in ELISA. Even the samples that showed a weak positive immunoreactivity in ELISA did not bind to live human sperm in IBT, indicating lack of sperm binding antibodies in these sera. In all these assays, the sera from immunoinfertile men were positive. Our findings indicate that chronic prostatitis, BPH and prostate cancer do not induce antibodies to spermatozoa, sperm-specific antigens and seminal plasma components. Although prostate is an immunologically competent organ, and its abnormalities cause a rise in circulating prostate-specific antigen (PSA), it appears that there is no concomitant induction of immunity to spermatozoa/seminal components including sperm-specific fertility-related antigens, thus not causing ASA-induced immunoinfertlity. This is the first study to our knowledge reporting the absence of ASA in men with BPH and prostate cancer. PMID- 22321001 TI - Oligonucleotide-directed gene-editing technology: mechanisms and future prospects. AB - INTRODUCTION: Gene editing, as defined here, uses short synthetic oligonucleotides to introduce small, site-specific changes into mammalian genomes, including repair of genetic point mutations. Early RNA-DNA oligonucleotides (chimeraplasts) were problematic, but application of single stranded all-DNA molecules (ssODNs) has matured the technology into a reproducible tool with therapeutic potential. AREAS COVERED: The review illustrates how gene-editing mechanisms are linked to DNA repair systems and DNA replication, and explains that while homologous recombination (HR) and nucleotide excision repair (NER) are implicated, the mismatch repair (MMR) system is inhibitory. Although edited cells often arrest in late S-phase or G2-phase, alternative ssODN chemistries can improve editing efficiency and cell viability. The final section focuses on the exciting tandem use of ssODNs with zinc finger nucleases to achieve high frequency genome editing. EXPERT OPINION: For a decade, changing the genetic code of cells via ssODNs was largely done in reporter gene systems to optimize methods and as proof-of-principle. Today, editing endogenous genes is advancing, driven by a clearer understanding of mechanisms, by effective ssODN designs and by combination with engineered endonuclease technologies. Success is becoming routine in vitro and ex vivo, which includes editing embryonic stem (ES) and induced pluripotent stem (iPS) cells, suggesting that in vivo organ gene editing is a future option. PMID- 22321002 TI - Does activation of the anti proton, rather than concertedness, determine the stereochemistry of base-catalyzed 1,2-elimination reactions? Anti stereospecificity in E1cB eliminations of beta-3-trifluoromethylphenoxy esters, thioesters, and ketones. AB - As part of a comprehensive investigation on the stereochemical aspects of base catalyzed 1,2-elimination reactions, we have studied a set of acyclic carbonyl substrates that react by an irreversible E1cB mechanism with largely anti stereospecificity. (2)H NMR data show that these reactions using KOH in EtOH/H(2)O under non-ion-pairing conditions produce a minimum of 85-89% anti elimination on stereospecifically labeled tert-butyl (2R*,3R*)- and (2R*,3S*)-3 (3-trifluoromethylphenoxy)-2,3-(2)H(2)-butanoate, S-tert-butyl (2R*,3R*)- and (2R*,3S*)-3-(3-trifluoromethylphenoxy)-2,3-(2)H(2)-butanethioate, and the related ketones, (4R*,5R*)- and (4R*,5S*)-5-(3-trifluoromethylphenoxy)-4,5-(2)H(2)-3 hexanone. With both diastereomers of each substrate available, the KIEs can be calculated and the innate stereoselectivities determined. The elimination reactions of the beta-3-trifluoromethylphenoxy substrates occur by E1cB mechanisms with diffusionally equilibrated enolate-anion intermediates. Thus, it is clear that anti elimination does not depend solely upon concerted E2 mechanisms. Negative hyperconjugation provides a satisfactory explanation for the anti stereospecificity exhibited by our carbonyl substrates, where the leaving group activates the anti proton, leading to the enolate intermediate. The activation of the anti proton by negative hyperconjugation may also play a role in the concerted pathways of E2 mechanisms. We have also measured the rates of the hydroxide-catalyzed elimination reactions of butanoate, thiobutanoate, and ketone substrates in EtOH/H(2)O, with beta-tosyloxy, acetoxy, and 3 trifluoromethylphenoxy nucleofuges. PMID- 22321003 TI - CTLA4-Ig prevents alloantibody production and BMT rejection in response to platelet transfusions in mice. AB - BACKGROUND: Platelet (PLT) transfusions can induce humoral and cellular alloimmunity. HLA antibodies can render patients refractory to subsequent transfusion, and both alloantibodies and cellular alloimmunity can contribute to subsequent bone marrow transplant (BMT) rejection. Currently, there are no approved therapeutic interventions to prevent alloimmunization to PLT transfusions other than leukoreduction. Targeted blockade of T-cell costimulation has shown great promise in inhibiting alloimmunity in the setting of transplantation, but has not been explored in the context of PLT transfusion. STUDY DESIGN AND METHODS: We tested the hypothesis that the costimulatory blockade reagent CTLA4-Ig would prevent alloreactivity against major and minor alloantigens on transfused PLTs. BALB/c (H-2(d)) mice and C57BL/6 (H-2(b)) mice were used as PLT donors and transfusion recipients, respectively. Alloantibodies were measured by indirect immunofluorescence using BALB/c PLTs and splenocytes as targets. BMTs were carried out under reduced-intensity conditioning using BALB.B (H-2(b) ) donors and C57BL/6 (H-2(b)) recipients to model HLA-identical transplants. Experimental groups were given CTLA4-Ig (before or after PLT transfusion) with control groups receiving isotype-matched antibody. RESULTS: CTLA4-Ig abrogated both humoral alloimmunization (H-2(d) antibodies) and transfusion-induced BMT rejection. Whereas a single dose of CTLA4-Ig at time of transfusion prevented alloimmunization to subsequent PLT transfusions, administration of CTLA4-Ig after initial PLT transfusion was ineffective. Delaying treatment until after PLT transfusion failed to prevent BMT rejection. CONCLUSIONS: These findings demonstrate a novel strategy using an FDA-approved drug that has the potential to prevent the clinical sequelae of alloimmunization to PLT transfusions. PMID- 22321004 TI - Evaluation of atmospheric PCDD/F depositions via automated and traditional water surface samplers in Taiwan. AB - Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) are a group of compounds of major environmental concern. Once emitted into the atmosphere, PCDD/Fs undergo photochemical reactions and enter other environmental compartments via wet and dry deposition. In this study, atmospheric PCDD/F depositions were collected via an automated PCDD/F deposition sampler and traditional cylindrical vessels, respectively, in northern, central, and southern Taiwan from 2008 to 2010. The automated PCDD/F precipitation sampler used in this study can prevent both resuspension and photodegradation of the PCDD/Fs collected and also effectively separates the PCDD/F samples into dry and wet contributions. The results indicate that the average atmospheric PCDD/F concentrations collected by the high-volume sampling trains were 13.6 +/- 10 (n = 10), 15.6 +/- 5.2 (n = 7), and 10.9 +/- 6.3 (n = 6) fg I-TEQ/m(3) in northern, central, and southern Taiwan, respectively. In addition, the results also indicate that the PCDD/F deposition flux collected with an automated PCDD/F sampler (1.84 +/- 0.90-8.68 +/ 5.1 pg I-TEQ/m(2)/day, n = 23) is significantly higher than that sampled with cylindrical vessels (1.11 +/- 0.69-5.64 +/- 5.2 pg I-TEQ/m(2)/day, n = 23). Based on the Mann-Whitney statistical analysis, the p value (0.037) of PCDD/F deposition flux between those two samplers measurement is lower than 0.05. The difference is attributed to the fact that part of the PCDD/F depositions collected by traditional cylindrical vessels is photodegraded and revolatilized. In addition, the wet deposition flux of PCDD/Fs (3.66 to 470 pg I-TEQ/m(2)/rainy day, n = 23) observed in Taiwan is significantly higher than the dry deposition flux (0.38 to 4.55 pg I-TEQ/m(2)/sunny day, n = 23). The results demonstrate that the wet deposition is the major PCDD/F removal mechanism in the atmosphere. Furthermore, the overall PCDD/Fs deposition velocity and scavenging (rainout) coefficient in Taiwan are calculated as 0.20 +/- 0.07 cm/s and 6.5 +/- 0.2 * 10(4), respectively. PMID- 22321005 TI - Plasmonic coupling in gold nanoring dimers: observation of coupled bonding mode. AB - We investigate the optical properties of gold nanoring (NR) dimers in both simulation and experiment. The resonance peak wavelength of gold NR dimers is strongly dependent on the polarization direction and gap distance. As the gold NR particles approach each other, exponential red shift and slight blue shift of coupled bonding (CB) mode in gold NR dimers for longitudinal and transverse polarizations are obtained. In finite element method analysis, a very strong surface plasmon coupling in the gap region of gold NR dimers is observed, whose field intensity at the gap distance of 10 nm is enhanced 23% compared to that for gold nanodisk (ND) dimers with the same diameter. In addition, plasmonic dimer system exhibits a great improvement in the sensing performance. Near-field coupling in gold NR dimers causes exponential increase in sensitivity to refractive index of surrounding medium with decreasing the gap distance. Compared with coupled dipole mode in gold ND dimers, CB mode in gold NR dimers shows higher index sensitivity. This better index sensing performance is resulted form the additional electric field in inside region of NR and the larger field enhancement in the gap region owing to the stronger coupling of collective dipole plasmon resonances for CB mode. These results pave the way to design plasmonic nanostructures for practical applications that require coupled metallic nanoparticles with enhanced electric fields. PMID- 22321006 TI - Evaluation of lactic acid bacterium from chilli waste as a potential antifungal agent for wood products. AB - AIMS: The aim of this study was to isolate lactic acid bacteria from chilli waste and evaluate metabolites produced for the ability to arrest wood decay. METHODS AND RESULTS: Using an optical density screening method, one bacterium (isolate C11) was identified as having pronounced antifungal properties against Oligoporus placenta. This isolate was identified as Lactobacillus brevis by 16S rRNA gene sequencing. To determine antifungal activity in wood, Pinus radiata blocks were impregnated with Lact. brevis [C11] cell-free supernatant and exposed to brown rot fungi O. placenta, Antrodia xantha and Coniophora puteana. The treated timber demonstrated resistance to degradation from all fungi. The antifungal metabolites were heat stable and not affected by proteinase K, but were affected by neutralization with NaOH suggesting the metabolites were of an acidic nature. The presence of lactic and acetic acid was confirmed by HPLC analysis. CONCLUSIONS: Lactobacillus brevis [C11] produced acidic metabolites that were able to inhibit the growth of wood decay fungi and subsequent wood decay. SIGNIFICANCE AND IMPACT OF THE STUDY: Traditional wood treatments are becoming an environmental issue as the public demands more benign options. The use of lactic acid bacteria which are considered safe for general use is a potential alternative to the conventional heavy metal chemicals currently in use. PMID- 22321007 TI - Practical guidelines on the use of paliperidone palmitate in schizophrenia. AB - OBJECTIVE: Paliperidone palmitate is an atypical long-acting injectable (LAI) antipsychotic that has been approved for use in the US, EU, Australia and numerous other countries for acute and maintenance therapy of schizophrenia. LAI antipsychotics are often viewed as a 'last-resort' treatment for difficult-to treat patients, however this article considers their role more broadly in the management of partial or non-adherence in schizophrenia. METHOD: A search of MedLine, CTR and PsychInfo was conducted to identify relevant publications and clinical trials (search term 'paliperidone palmitate', up to December 2010). The findings were discussed in a number of teleconferences and the manuscript was finalized with a face-to-face meeting of the authors group. MAIN FINDINGS: Relapse prevention in schizophrenia requires a comprehensive approach to treatment, which includes antipsychotic medication and psychosocial measures as well as family and/or carer involvement. Good symptom control and the interconnected issue of treatment adherence are arguably the most crucial factors for success. Carer and patient feedback should be carefully considered. Negotiation about commencing LAI therapy done early in course of disease is easier than many clinicians believe, although it is not often attempted in practice. Paliperidone palmitate is useful in both the acute and maintenance phases of treatment. COMMENTARY: A case-based approach is presented to suggest various opportunities where use of paliperidone palmitate could be considered within the disease course of schizophrenia. CONCLUSIONS: Paliperidone palmitate offers some advantages in terms of tolerability, simplicity of treatment initiation and long duration between injections. The consensus of the authors is that rather than reserving paliperidone palmitate for use in difficult-to-treat or refractory patients, it could be used to promote adherence and prevent relapse earlier in the course of the illness. PMID- 22321008 TI - Meta-analysis of alpha2-adrenergic agonists versus carbonic anhydrase inhibitors as adjunctive therapy. AB - OBJECTIVE: To evaluate the efficacy of alpha2-adrenergic agonist (AA) brimonidine and topical carbonic anhydrase inhibitors (CAIs) dorzolamide and brinzolamide in reducing intraocular pressure (IOP) when used as adjunctive therapy to beta blockers (BBs) or prostaglandin analogs (PGAs). RESEARCH DESIGN AND METHODS: Pertinent publications were identified through systematic searches of PubMed, EMBASE, and the Cochrane Controlled Trials Register. Randomized controlled trials comparing AA with CAIs in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT) who had inadequate IOP control with monotherapy of a BB or PGA. The weighted mean differences (WMD) of IOP-lowering efficacy were calculated by performing meta-analysis. MAIN OUTCOME MEASURES: The main efficacy measures were the reduction from baseline to end of treatment in IOP at peak, trough, and diurnal curve. RESULTS: Eleven published randomized clinical trials involving 1493 patients were included in the meta-analysis. As adjunctive therapy, the IOP reduction was greater in the brimonidine group than in the CAI group at peak (WMD: 0.99 mmHg [95% confidence interval, 0.45 to 1.53]) and diurnal curve (WMD: 0.62 mmHg [0.07 to 1.18]). As adjunctive therapy to BBs, brimonidine was more effective than CAIs in reducing IOP at peak (WMD: 0.85 mmHg [0.42 to 1.29]) and trough (WMD: 0.47 mmHg [0.12 to 0.83]). As adjunctive therapy to PGAs, brimonidine resulted greater reduction in peak IOP than CAIs (WMD: 1.04 mmHg [0.08 to 2.00]). CONCLUSIONS: Brimonidine provides greater IOP-lowering efficacy than topical carbonic anhydrase inhibitors as adjunctive therapy to BBs or PGAs. PMID- 22321009 TI - Ciprofloxacin photosensitized oxidation of 2'-deoxyguanosine-5'-monophosphate in neutral aqueous solution. AB - Laser flash photolysis studies have been carried out to investigate the reactions of ciprofloxacin (CPX) with 2'-deoxyguanosine-5'-monophosphate (dGMP), N, N, N', N'-tetramethyl-p-phenylenediamine (TMPD) and ferulic acid (FCA) in neutral aqueous solutions, respectively. CPX triplet state ((3)CPX*) can be quenched by TMPD, FCA and dGMP, with rate constants of 1.8 * 10(9), 1.5 * 10(9) and 5.8 * 10(7) dm(3) mol(-1) s(-1), respectively. TMPD radical cation (TMPD(.+)) and FCA radical cation (FCA(.+)) were observed directly. The formation rate of CPX radical anion (CPX(.-)) was determined to be 1.5 * 10(9) dm(3) mol(-1) s(-1). Redox reaction of dGMP was investigated through competing reactions using TMPD and FCA as probe. The triplet energy of CPX was determined to be 262 kJ mol(-1). Electron transfer from TMPD, FCA and dGMP to (3)CPX* was proposed. PMID- 22321010 TI - Integrated cellular pathology-systems biology of human diseases. PMID- 22321011 TI - Protein phosphatase 1alpha interacting proteins in the human brain. AB - Protein Phosphatase 1 (PP1) is a major serine/threonine-phosphatase whose activity is dependent on its binding to regulatory subunits known as PP1 interacting proteins (PIPs), responsible for targeting PP1 to a specific cellular location, specifying its substrate or regulating its action. Today, more than 200 PIPs have been described involving PP1 in panoply of cellular mechanisms. Moreover, several PIPs have been identified that are tissue and event specific. In addition, the diversity of PP1/PIP complexes can further be achieved by the existence of several PP1 isoforms that can bind preferentially to a certain PIP. Thus, PP1/PIP complexes are highly specific for a particular function in the cell, and as such, they are excellent pharmacological targets. Hence, an in-depth survey was taken to identify specific PP1alpha PIPs in human brain by a high throughput Yeast Two-Hybrid approach. Sixty-six proteins were recognized to bind PP1alpha, 39 being novel PIPs. A large protein interaction databases search was also performed to integrate with the results of the PP1alpha Human Brain Yeast Two-Hybrid and a total of 246 interactions were retrieved. PMID- 22321012 TI - A molecular case report of autosomal dominant retinitis pigmentosa: RP1/RHO sequence variants in a Turkish family. AB - Retinitis pigmentosa (RP) is an inherited progressive retinal disease with a complex inheritance pattern affecting about 1 in 3,500 people worldwide. To date, a large number of sequence changes in the causal contributor genes of wide spectrum heterogeneous RP were reported, including deletions, insertions, or substitutions that lead missense mutations or truncations. Here we present an association between the clinical presentations of adRP and sequence variants involving novel M216L mutation in the RHO gene together with nonsynonimous sequence changes R872H, N985Y, A1670T, S1691P, C2033Y, and synonimous Q1725Q with novel, N1521N, and T1733T SNPs in the RP1 gene of uncertain pathogenicity in a Turkish family with autosomal dominant retinitis pigmentosa. PMID- 22321013 TI - Cross-analysis of gene and miRNA genome-wide expression profiles in human fibroblasts at different stages of transformation. AB - We have developed a cellular system constituted of human telomerase immortalized fibroblasts that gradually underwent neoplastic transformation during propagation in culture. We exploited this cellular system to investigate gene and miRNA transcriptional programs in cells at different stages of propagation, representing five different phases along the road to transformation, from non transformed cells up to tumorigenic and metastatic ones. Here we show that gene and miRNA expression profiles were both able to divide cells according to their transformation phase. We identified more than 1,700 genes whose expression was highly modulated in cells at at least one propagation stage and we found that the number of modulated genes progressively increased at successive stages of transformation. These genes identified processes significantly deregulated in tumorigenic cells, such as cell differentiation, cell movement and extracellular matrix remodeling, cell cycle and apoptosis, together with upregulation of several cancer testis antigens. Alterations in cell cycle, apoptosis, and cancer testis antigen expression were particular hallmarks of metastatic cells. A parallel deregulation of a panel of 43 miRNAs strictly connected to the p53 and c Myc pathways and with oncogenic/oncosuppressive functions was also found. Our results indicate that cen3tel cells can be a useful model for human fibroblast neoplastic transformation, which appears characterized by complex and peculiar alterations involving both genetic and epigenetic reprogramming, whose elucidation could provide useful insights into regulatory networks underlying cancerogenesis. PMID- 22321014 TI - Integrating the Alzheimer's disease proteome and transcriptome: a comprehensive network model of a complex disease. AB - Network models combined with gene expression studies have become useful tools for studying complex diseases like Alzheimer's disease. We constructed a "Core" Alzheimer's disease protein interaction network by human curation of the primary literature. The Core network consisted of 775 nodes and 2,204 interactions. To our knowledge, this is the most comprehensive and accurate protein interaction network yet constructed for Alzheimer's disease. An "Expanded" network was computationally constructed by adding additional proteins that interacted with Core network proteins, and consisted of 4,945 nodes and 26,064 interactions. We then mapped existing gene expression studies to the Core network. This combined data model identified the MAPK/ERK pathway and clathrin-mediated receptor endocytosis as key pathways in Alzheimer's disease. Important proteins in the MAPK/ERK pathway that interacted in the Core network formed a downregulated cluster of nodes, whereas clathrin and several clathrin accessory proteins that interacted in the Core network formed an upregulated cluster of nodes. The MAPK/ERK pathway is a key component in synaptic plasticity and learning, processes disrupted in Alzheimer's. Clathrin and clathrin adaptor proteins are involved in the endocytosis of the APP protein that can lead to increased intracellular levels of amyloid beta peptide, contributing to the progression of Alzheimer's. PMID- 22321015 TI - Recombinant human prion protein fragment 90-231, a useful model to study prion neurotoxicity. AB - Transmissible spongiform encephalopathies (TSE), or prion diseases, are a group of fatal neurodegenerative disorders of animals and humans. Human diseases include Creutzfeldt-Jakob (CJD) and Gerstmann-Straussler-Scheinker (GSSD) diseases, fatal familial insomnia, and Kuru. Human and animal TSEs share a common histopathology with a pathognomonic triad: spongiform vacuolation of the grey matter, neuronal death, glial proliferation, and, more inconstantly, amyloid deposition. According to the "protein only" hypothesis, TSEs are caused by a unique post-translational conversion of normal, host-encoded, protease-sensitive prion protein (PrP(sen) or PrP(C)) to an abnormal disease-associated isoform (PrP(res) or PrP(Sc)). To investigate the molecular mechanism of neurotoxicity induced by PrP(Sc) we developed a protocol to obtain millimolar amounts of soluble recombinant polypeptide encompassing the amino acid sequence 90-231 of human PrP (hPrP90-231). This protein corresponds to the protease-resistant prion protein fragment that originates after amino-terminal truncation. Importantly, hPrP90-231 has a flexible backbone that, similar to PrP(C), can undergo to structural rearrangement. This peptide, structurally resembling PrP(C), can be converted in a PrP(Sc)-like conformation, and thus represents a valuable model to study prion neurotoxicity. In this article we summarized our experimental evidence on the molecular and structural mechanisms responsible of hPrP90-231 neurotoxicity on neuroectodermal cell line SHSY5Y and the effects of some PrP pathogen mutations identified in familial TSE. PMID- 22321016 TI - Cognitive disorders in mice: cytokine signaling pathways as therapeutic targets. AB - Surplus accumulation of regulatory T cells (Tregs) is known to be at the bottom of many morbid conditions, among them being neuropsychiatric diseases. In particular, Tregs may inhibit Th1 cells, including brain autoimmune lymphocytes, controlling the local microglial response and brain tissue homeostasis. The present study was undertaken in an attempt to suggest a novel approach for the treatment of maladaptation to mental stress associated with excessive Treg accumulation. Recently it was shown that alkylating drugs (ADs), such as melphalan and cyclophosphamide (Cy) in the dose 100-fold lower than cytostatic one are capable to disturb signal transduction by IL-2R. In this study we demonstrated that IL-2R is not a unique receptor, which may be blocked with ADs. Similar effect has been shown for two other surface receptors: TNFR and Fas. Molecular mechanisms of the receptor blockage were investigated on the model of TNF signaling. Study of NF-kappaB activity in nuclear extracts showed that alkylating agents act at the level of surface receptor or of the receptor platform. It was also shown that ADs administration in ultralow doses results in selective elimination of Tregs. In this study we used a new laboratory model of Treg accumulation in mice. Such Treg accumulation was associated with cognitive and behavioral abnormalities, which may be prevented by Cy administration. PMID- 22321017 TI - Post-extracorporeal shockwave lithotripsy residual stone fragments: clinical significance and management. AB - Although extracorporeal shockwave lithotripsy (ESWL) is one of the primary treatments for urolithiasis, very often residual fragments of the calculi are still present for a long time after the ESWL session. These fragments are usually asymptomatic and can be managed expectantly, but sometimes they can cause symptoms and require intervention. Secondary procedures are not routinely applied to all patients with residual fragments, but only to those with significant symptoms. Medical therapy may play an important role in the management of residual fragments, by correcting an underlying metabolic disorder and by preventing the growth of residual calculi and the formation of new ones. PMID- 22321018 TI - Contrast tuned responses in primary auditory cortex of the awake ferret. AB - Auditory neurons are often characterized by their spectro-temporal receptive field (STRF), a linear measure that captures overall trends of neural responses to modulations of the spectro-temporal envelopes of sounds. We have previously shown that primary auditory cortex neurons of the awake ferret are better characterized by STRFs followed by a non-trivial non-linearity. This non linearity is a half-wave rectification followed by a squaring function, indicating that cortical neurons probably encode higher-order statistics of the spectrum of sounds. In this article, we introduce the concept of a contrast receptive field (CRF) and show that neurons in the auditory cortex encode quadratic statistics of the spectro-temporal envelope of sounds, which we call auditory contrast. We reveal phase-dependent contrast tuning in single units. Most units with a reliable STRF also possess a reliable CRF, such that the response to stimulus contrast complements the linear response described by the STRF. The relationship between the STRF and the CRF is analyzed in terms of orthogonality, co-localization in time-frequency, feature orientation selectivity, and output non-linearity interdependence. Our study shows that contrast can be used by auditory cortex neurons to sharpen, in a noise-resistant fashion, their responses to dynamic spectral profiles. PMID- 22321019 TI - Comparative dynamics of four smoking withdrawal symptom scales. AB - AIMS: To examine the association of person-specific trajectories of withdrawal symptoms of urge-to-smoke, negative affect, physical symptoms and hunger during the first 7 days after smoking cessation with abstinence at end of treatment (EOT) and at 6 months. DESIGN: Hierarchical linear modeling (HLM) was used to model person-specific trajectory parameters (level, slope, curvature and volatility) for withdrawal symptoms. SETTING: University-based smoking cessation trials. PARTICIPANTS: Treatment-seeking smokers in clinical trials of transdermal nicotine versus nicotine spray (n = 514) and bupropion versus placebo (n = 421). MEASUREMENTS: Self-reported withdrawal symptoms for 7 days after the planned quit date, and 7-day point prevalence and continuous abstinence at EOT and 6 months. FINDINGS: In regressions that included trajectory parameters for one group of withdrawal symptoms, both urge-to-smoke and negative affect were predictive of abstinence while physical symptoms and hunger were generally not predictive. In stepwise regressions that included the complete set of trajectory parameters across withdrawal symptoms (for urge-to-smoke, negative affect, physical symptoms and hunger), with a single exception only the trajectory parameters for urge-to-smoke were predictive. Area under the receiver operator characteristic curve was 0.594 for covariates alone, and 0.670 for covariates plus urge-to-smoke trajectory parameters. CONCLUSIONS: Among a number of different withdrawal symptoms (urge-to-smoke, negative affect, physical symptoms and hunger) urge-to-smoke trajectory parameters (level, slope and volatility) over the first 7 days of smoking cessation show the strongest prediction of both short- and long-term relapse. Other withdrawal symptoms increase the predictive ability by negligible amounts. PMID- 22321020 TI - Orbital-resolved partial charge transfer from the methoxy groups of substituted pyrenes in complexes with tetracyanoquinodimethane--a NEXAFS study. AB - It is demonstrated that the near-edge X-ray absorption fine structure (NEXAFS) provides a powerful local probe of functional groups in novel charge transfer (CT) compounds and their electronic properties. Microcrystals of tetra /hexamethoxypyrene as donors with the strong acceptor tetracyano-p-quinodimethane (TMP/HMP-TCNQ) were grown by vapor diffusion. The oxygen and nitrogen K-edge spectra are spectroscopic fingerprints of the functional groups in the donor and acceptor moieties, respectively. The orbital selectivity of the NEXAFS pre-edge resonances allows us to precisely elucidate the participation of specific orbitals in the charge transfer process. Upon complex formation, the intensities of several resonances change substantially and a new resonance occurs in the oxygen K-edge spectrum. This gives evidence of a corresponding change of hybridization of specific orbitals in the functional groups of the donor (those derived from the frontier orbitals 2e and 6a(1) of the isolated methoxy group) and acceptor (orbitals b(3g), a(u), b(1g), and b(2u), all located at the cyano group) with pi*-orbitals of the ring systems. Along with this intensity effect, the resonance positions associated with the oxygen K-edge (donor) and nitrogen K edge (acceptor) shift to higher and lower photon energies in the complex, respectively. A calculation based on density functional theory qualitatively explains the experimental results. NEXAFS measurements shine light on the action of the functional groups and elucidate charge transfer on a submolecular level. PMID- 22321021 TI - Cartwheel retinopathy. AB - A case of Valsalva retinopathy is presented, with a discussion of treatment options. PMID- 22321022 TI - Dickkopf-1 inhibits epithelial-mesenchymal transition of colon cancer cells and contributes to colon cancer suppression. AB - This study aimed to determine the expression pattern of dickkopf-1 (Dkk1), a potent inhibitor of Wnt signaling, in colon cancer and to assess the function and mechanism of Dkk1 in tumor progression in vitro and in vivo. We detected the protein expression of Dkk1 and some epithelial-mesenchymal transition (EMT) associated markers (E-cadherin, vimentin and beta-catenin) in 217 tissue samples of human colon cancer, upregulated Dkk1 expression in HCT116 colon cancer cells, and established a nude mouse xenograft model. Dkk1 protein overexpression was inversely related to tumor grade and the presence of metastasis and recurrence of colon cancer. Notably, the expression of Dkk1 was concomitant with reduced immunohistochemical features of EMT (e.g. increased expression of epithelial marker E-cadherin, decreased expression of mesenchymal marker vimentin, and cytoplasmic distribution of beta-catenin). Furthermore, Dkk1 overexpression resulted in restoration of the epithelial phenotype, decreased expression of EMT transcription factors Snail and Twist, and decreased expression of markers suggestive of intestinal stem cells (e.g. cluster of differentiation 133 [CD133] and leucine-rich-repeat-containing G-protein-coupled receptor 5 [Lgr5]). Functional analysis showed overexpression of Dkk1 reduced proliferation, migration, and invasion of colon cancer cells. Moreover, upregulation of Dkk1 led to decreased tumor-initiating ability and suppressed colon tumor growth in nude mice. Our findings indicate that Dkk1 can suppress the progression of colon cancer, possibly through EMT inhibition, and could therefore serve as a target for tumor therapy. PMID- 22321023 TI - Postsynthetic on column RNA labeling via Stille coupling. AB - Stille Coupling is a versatile C-C bond forming reaction with high functional group tolerance under mild conditions. Our on column synthesis concept for RNA modification is based on the incorporation of iodo substituted nucleotide precursors to RNA during automated standard solid phase synthesis via TBDMS-, TC , and ACE- protecting group strategies. Subsequently, the RNA, still bound on solid support, is ready for orthogonal postsynthetic functionalization via Stille cross-couplings utilizing the advantages of solid phase synthesis. Several monomer test reactions were employed with 2-iodo adenosine and 5-iodo uridine and organostannanes as coupling partners under different conditions, changing the catalyst/ligand system, temperature, and reaction time as well as conventional heating and microwave irradiation. Finally, Stille cross-couplings under optimized conditions were transferred to fully protected 5-mer and 12-mer RNA oligonucleotides on-column. Deprotection and cleavage from solid support resulted in site-specifically labeled oligonucleotides. Derivatizations via Stille cross couplings were performed initially with vinyltributylstannane as well as later with 2-furanyl-, 2-thiophene-, and benzothiophene-2-tributylstannanes yielding fluorescently functionalized RNA. PMID- 22321024 TI - Recent progress toward understanding the physiological function of bone marrow mesenchymal stem cells. AB - Mesenchymal stem cells (MSCs) are multipotent cells that are being clinically explored as regenerative therapeutics. Cultured MSCs secrete various modulatory factors, which contribute to the immunosuppressive effects of transplanted MSCs as a therapy. Although the in vitro phenotype of MSCs has been well characterized, identification of MSCs in vivo is made difficult by the lack of specific markers. Current advances in murine MSC research provide valuable tools for studying the localization and function of MSCs in vivo. Recent findings suggest that MSCs exert diverse functions depending on tissue context and physiological conditions. This review focuses on bone marrow MSCs and their roles in haematopoiesis and immune responses. PMID- 22321025 TI - Quantifying the total and bioavailable polycyclic aromatic hydrocarbons and dioxins in biochars. AB - Biochar soil amendment is advocated to mitigate climate change and improve soil fertility. A concern though, is that during biochar preparation PAHs and dioxins are likely formed. These contaminants can possibly be present in the biochar matrix and even bioavailable to exposed organisms. Here we quantify total and bioavailable PAHs and dioxins in a suite of over 50 biochars produced via slow pyrolysis between 250 and 900 degrees C, using various methods and biomass from tropical, boreal, and temperate areas. These slow pyrolysis biochars, which can be produced locally on farms with minimum resources, are also compared to biochar produced using the industrial methods of fast pyrolysis and gasification. Total concentrations were measured with a Soxhlet extraction and bioavailable concentrations were measured with polyoxymethylene passive samplers. Total PAH concentrations ranged from 0.07 MUg g(-1) to 3.27 MUg g(-1) for the slow pyrolysis biochars and were dependent on biomass source, pyrolysis temperature, and time. With increasing pyrolysis time and temperature, PAH concentrations generally decreased. These total concentrations were below existing environmental quality standards for concentrations of PAHs in soils. Total PAH concentrations in the fast pyrolysis and gasification biochar were 0.3 MUg g(-1) and 45 MUg g( 1), respectively, with maximum levels exceeding some quality standards. Concentrations of bioavailable PAHs in slow pyrolysis biochars ranged from 0.17 ng L(-1) to 10.0 ng L(-1)which is lower than concentrations reported for relatively clean urban sediments. The gasification produced biochar sample had the highest bioavailable concentration (162 +/- 71 ng L(-1)). Total dioxin concentrations were low (up to 92 pg g(-1)) and bioavailable concentrations were below the analytical limit of detection. No clear pattern of how strongly PAHs were bound to different biochars was found based on the biochars' physicochemical properties. PMID- 22321026 TI - Elvitegravir: a once-daily inhibitor of HIV-1 integrase. AB - INTRODUCTION: Elvitegravir (EVG) is a potent inhibitor of HIV-1 integrase (IN) undergoing Phase III clinical trials. It blocks the strand-transfer step in a multi-step process that allows double-stranded cDNA to be irreversibly incorporated within the host DNA. It is the second member of the HIV-1 IN inhibitor class, following raltegravir. Co-administration with a CYP3A inhibitor, such as ritonavir or cobicistat, substantially increases EVG plasma exposure and prolongs elimination half-life. AREAS COVERED: A Medline review of Phase II and III trials involving EVG as well as a review of abstracts from major HIV and infectious disease conferences from 2010 to 2011 was conducted. EVG produces rapid and durable virologic suppression when combined with active background therapy. Trials investigating the efficacy of once-daily co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir (EVG/COBI/FTC/TDF) demonstrate a high rate of virologic suppression with fewer CNS and psychiatric adverse events compared with co-formulated efavirenz/emtricitabine/tenofovir. The resistance profile for EVG is similar to raltegravir. EXPERT OPINION: Co-formulated EVG/COBI/FTC/TDF is an option for the treatment of antiretroviral naive and experienced patients. Once-daily dosing offers an advantage over raltegravir, but the requirement for pharmacologic boosting increases regimen complexity. Dolutegravir in development offers a favorable resistance profile and no requirement for pharmacologic boosting. PMID- 22321027 TI - Preventing flow-metabolism uncoupling acutely reduces axonal injury after traumatic brain injury. AB - We have previously presented evidence that the development of secondary traumatic axonal injury is related to the degree of local cerebral blood flow (LCBF) and flow-metabolism uncoupling. We have now tested the hypothesis that augmenting LCBF in the acute stages after brain injury prevents further axonal injury. Data were acquired from rats with or without acetazolamide (ACZ) that was administered immediately following controlled cortical impact injury to increase cortical LCBF. Local cerebral metabolic rate for glucose (LCMRglc) and LCBF measurements were obtained 3 h post-trauma in the same rat via 18F-fluorodeoxyglucose and 14C iodoantipyrine co-registered autoradiographic images, and compared to the density of damaged axonal profiles in adjacent sections, and in additional groups at 24 h used to assess different populations of injured axons stereologically. ACZ treatment significantly and globally elevated LCBF twofold above untreated injured rats at 3 h (p<0.05), but did not significantly affect LCMRglc. As a result, ipsilateral LCMRglc:LCBF ratios were reduced by twofold to sham-control levels, and the density of beta-APP-stained axons at 24 h was significantly reduced in most brain regions compared to the untreated-injured group (p<0.01). Furthermore, early LCBF augmentation prevented the injury-associated increase in the number of stained axons from 3-24 h. Additional robust stereological analysis of impaired axonal transport and neurofilament compaction in the corpus callosum and cingulum underlying the injury core confirmed the amelioration of beta-APP axon density, and showed a trend, but no significant effect, on RMO14-positive axons. These data underline the importance of maintaining flow-metabolism coupling immediately after injury in order to prevent further axonal injury, in at least one population of injured axons. PMID- 22321028 TI - Endometrial response to concurrent treatment with vaginal progesterone and transdermal estradiol. AB - ABSTRACT Objective To describe the effect of the intermittent administration of vaginal progesterone and a low-dose estradiol patch on endometrial stability, as assessed by the rate of amenorrhea and endometrial stimulation. Methods This was an open study in which 64 moderately symptomatic, postmenopausal women were treated in the outpatient clinic of our University Hospital for different intervals up to 1 year. The treatment consisted of a combination of patches delivering 25 ug/day estradiol and intravaginal pills containing 100 mg of micronized progesterone. Patches and pills were administered concomitantly in a twice-a-week protocol. The endometrial response was assessed by endovaginal ultrasound completed with suction biopsy when required. Results Both cumulative amenorrhea and no-bleeding rates increased progressively and reached 88.9% and 100.0%, respectively, by the 12th month. Isolated or repetitive episodes of bleeding, bleeding and spotting, or only spotting were reported by three, four, and 12 women, respectively. Endometrial thickness remained unaltered. Endometrium was atrophic in the seven women in whom a biopsy was performed. Conclusion The substantially reduced progestogen load determined by this combination achieved an acceptable incidence of spotting or bleeding when associated with a low estrogenic dose. There was no apparent endometrial stimulation. Additional studies are required to confirm this observation. PMID- 22321029 TI - Effects of polypharmacy on outcome in patients with schizophrenia in routine psychiatric treatment. AB - OBJECTIVE: Evaluating the effects of different types of psychotropic polypharmacy on clinical outcomes and quality of life (QOL) in 374 patients with schizophrenia and schizoaffective disorder in routine care. METHOD: Psychotropic regimen, clinical outcomes, and QOL were assessed before discharge and after 6, 12, 18, and 24 months. Data were analyzed by mixed-effects regression models for longitudinal data controlling for selection bias by means of propensity scores. RESULTS: At baseline 22% of participants received antipsychotic monotherapy (APM) (quetiapine, olanzapine, or risperidone), 20% more than one antipsychotic drug, 16% received antipsychotics combined with antidepressants, 16% antipsychotics plus benzodiazepines, 11.5% had antipsychotics and mood stabilizers, and 16% psychotropic drugs from three or more subclasses. Patients receiving APM had better clinical characteristics and QOL at baseline. Patients receiving i) antipsychotics plus benzodiazepines or ii) antipsychotics plus drugs from at least two additional psychotropic drug categories improved less than patients with APM. CONCLUSION: Combinations of antipsychotics with other psychotropic drugs seem to be effective in special indications. Nevertheless, combinations with benzodiazepines and with compounds from multiple drug classes should be critically reviewed. It is unclear whether poorer outcomes in patients with such treatment are its result or its cause. PMID- 22321030 TI - Adverse reactions, psychological factors, and their effect on donor retention in men and women. AB - BACKGROUND: This study investigates the effect of a vasovagal reaction (VVR) or needle reaction (NR) on the risk of stopping as a blood donor, taking into account variables from the Theory of Planned Behavior (TPB). Is stopping risk solely related to the adverse reaction itself, or do the TPB variables play a role as well? Emphasis is placed on possible sex differences. STUDY DESIGN AND METHODS: TPB variables were assessed within 12,051 whole blood donors. Also, donors reported the occurrence of adverse reactions during or after their last donation. Blood bank records were used to determine whether donors stopped donating within the next 2 years. Logistic regression analyses were performed to estimate the effect of self-reported adverse reactions on stopping risk, adjusting for the TPB variables. Analyses were performed separately for both sexes. RESULTS: Men have a lower odds of reporting a NR or a VVR than women (odds ratio [OR] 0.34, 95% confidence interval [CI], 0.28-0.43; and OR 0.26, 95% CI 0.19-0.36, for NR and VVR, respectively). For both sexes, only a VVR was associated with stopping risk, which is higher in men (men, OR 3.95, 95% CI 2.19 7.11; women, OR 1.78, 95% CI 1.35-2.35). After adjusting for the TPB variables both ORs declined (men, OR 3.38, 95% CI 1.86-6.15; women, OR 1.58, 95% CI 1.17 2.14). Also, self-efficacy and affective attitude are negatively associated with adverse reactions. CONCLUSION: Female donors report more VVRs than male donors, but male donors have a higher stopping risk after a VVR than female donors. Coping differences and possible reporting tendencies might play a role. For donor retention purposes, prevention and coping techniques should take sex differences into account. PMID- 22321031 TI - Terpenoids of methanol extract of Clerodendrum infortunatum exhibit anticancer activity against Ehrlich's ascites carcinoma (EAC) in mice. AB - CONTEXT: Clerodendrum infortunatum Linn. is a widely used plant in the Indian indigenous system of medicine for the treatment of tumors. OBJECTIVE: The present study evaluated the anticancer activity of methanol extract of C. infortunatum (MECI) against Ehrlich's ascites carcinoma (EAC) bearing Swiss albino mice and isolation of bioactive terpenoids from it. METHODS: HPLC analysis of the methanol extract showed the presence of three major components. Out of those, two compounds were isolated and characterized as oleanolic acid and clerodinin A. The anticancer activity of MECI was assessed by measuring the tumor growth response, percentage increase of life span, study of hematological parameters, lipid peroxidation, antioxidant enzyme activity like glutathion and CAT. In vitro cytotoxicity assay was also performed using EAC cell lines. RESULT AND CONCLUSION: Treatment with MECI causes significant decrease in the tumor cell volume and increase in the life span. The median survival time (MST) of EAC control group was found as 19.42 +/- 0.91 d, whereas the MST was increased to 23.44 +/- 2.69 d and 27.57 +/- 2.57 d for the groups treated with MECI at 100 and 200 mg/kg, respectively. All the hematological parameters, malonaldehyde content and antioxidant enzymes' activity were restored towards the normal level. IC(50) value of MECI was found as 498.33 ug/mL in cytotoxicity study. The experimental results suggested that MECI has significant anticancer activity, which can be attributed to the presence of oleanolic acid and clerodinin A. PMID- 22321032 TI - Curative treatment with extracts of Bombax ceiba fruit reduces risk of calcium oxalate urolithiasis in rats. AB - CONTEXT: Drawbacks of presently available treatments for urolithiasis necessitate finding the treatment of hyperoxaluria specifically aimed at reduction in oxalate excretion. Interestingly, many Indian tribes use Bombax ceiba L. (Bombacaceae) fruits as a traditional medicine for the treatment of urinary stones. OBJECTIVE: The present study investigated the efficacy of B. ceiba fruit extracts as curative agents in experimentally induced calcium oxalate urolithiatic rats. MATERIALS AND METHODS: Calcium oxalate lithiasis was induced in rats by oral administration of 0.75% ethylene glycol for 14 consecutive days. Treatments with aqueous and ethanol extract of B. ceiba fruit (400 mg/kg body weight) was performed in the same manner for further 14 consecutive days. Cystone (750 mg/kg body weight) was used as reference antiurolithiatic drug. The urinary excretion and kidney deposition of offending salt components, and serum biochemical parameters were investigated. RESULTS: Oral administration of ethylene glycol resulted in hyperoxaluria and increased renal excretion of calcium and phosphate. However, supplementation with aqueous and ethanol extracts of B. ceiba fruit significantly (p < 0.05) reduced the elevated urinary oxalate, showing a regulatory action on endogenous oxalate synthesis. The increased deposition of stone forming constituents in kidneys of calculogenic rats was also significantly lowered with curative treatment of aqueous and ethanol extract. DISCUSSION AND CONCLUSION: The results indicate that the fruit of B. ceiba is endowed with lithontriptic activity warranting further development for curative treatment of urolithiasis. PMID- 22321033 TI - Laparoscopic or open cholecystectomy in cirrhosis: a systematic review of outcomes and meta-analysis of randomized trials. AB - BACKGROUND: Cholecystectomy is associated with increased risks in patients with cirrhosis. The well-established advantages of laparoscopic surgery may be offset by the increased risk for complications relating particularly to portal hypertension and coagulopathy. METHODS: A systematic search was undertaken to identify studies comparing open cholecystectomy (OC) and laparoscopic cholecystectomy (LC) in patients with cirrhosis. A meta-analysis was performed of the available randomized controlled trials (RCTs). RESULTS: Forty-four studies were analysed. These included a total of 2005 patients with cirrhosis who underwent laparoscopic (n= 1756) or open (n= 249) cholecystectomy, with mortality rates of 0.74% and 2.00%, respectively. A meta-analysis of three RCTs involving a total of 220 patients was conducted. There was a reduction in the overall incidences of postoperative complications and infectious complications and a shorter length of hospital stay in LC. However, frequencies of postoperative hepatic insufficiency did not differ significantly. CONCLUSIONS: There are few RCTs comparing OC and LC in patients with cirrhosis. These studies are small, heterogeneous in design and include almost exclusively patients with Child-Pugh class A and B disease. However, LC appears to be associated with shorter operative time, reduced complication rates and reduced length of hospital stay. PMID- 22321034 TI - Analysis of survival predictors in a prospective cohort of patients undergoing transarterial chemoembolization for hepatocellular carcinoma in a single Canadian centre. AB - BACKGROUND: Despite advances in the treatment of hepatocellular carcinoma (HCC), a great proportion of patients are eligible only for palliative therapy for reasons of advanced-stage disease or poor hepatic reserve. The use of transarterial chemoembolization (TACE) in the palliation of non-resectable HCC has shown a survival benefit in European and Asian populations. The aim of this study was to assess the efficacy of TACE by analysing overall 5-year survival, interval changes of tumour size and serum alpha-fetoprotein (AFP) levels in a prospective North American cohort. METHODS: From September 2005 to December 2010, 46 candidates for TACE were enrolled in the study. Collectively, they underwent 102 TACE treatments. Data on tumour response, serum AFP and survival were prospectively collected. RESULTS: In compensated cirrhotic patients, serial treatment with TACE had a stabilizing effect on tumour size and reduced serum AFP levels during the first 12 months. Overall survival rates at 1, 2 and 3 years were 69%, 58% and 20%, respectively. Younger individuals and patients with a lower body mass index, affected by early-stage HCC with involvement of a single lobe, had better survival in univariate analysis. After adjustment for risk factors, early tumour stage (T1 and T2 vs. T3 and T4) at diagnosis was the only statistically significant predictor for survival. CONCLUSIONS: In compensated cirrhotic patients, TACE is an effective palliative intervention and HCC stage at diagnosis seems to be the most important predictor of longterm outcomes. PMID- 22321035 TI - Outcome after laparoscopic enucleation for non-functional neuroendocrine pancreatic tumours. AB - BACKGROUND: Non-functional endocrine pancreatic tumours (NPT) of more than 2 cm have an increased risk of malignancy. The aim of the present study was: (i) to define the guidelines for laparoscopic enucleation (LapEn) in patients with a non functional NPT <=3 cm in diameter; (ii) to evaluate pancreas-related complications; and (iii) to present the long-term outcome. METHODS: Between April 1998 and September 2010, 30 consecutive patients underwent laparoscopic surgery for a non-functional NPT (median age 56.5 years, range 44-83). Only 13 patients with tumours <=3 cm in size underwent LapEn. Local lymph node dissection to exclude lymph node involvement was performed in all patients. RESULTS: The median tumour size, operative time and blood loss were 2.8 cm (range 2.8-3), 130 min (range 90-280) and 220 ml (range 120-300), respectively. A pancreatic fistula occurred in five patients: International Study Group of Pancreatic Fistula (ISGPF) A in two patients and ISGPF B in three patients. The median follow-up was 48 months (12-144). Three patients with well-differentiated carcinoma are free of disease 2, 3 and 4 years after LapEn and a regional lymphadenectomy. One patient, 5 years after a LapEn, presented with lymph node and liver metastases. CONCLUSIONS: The present study confirms the technical feasibility and acceptable morbidity associated with LapEn. Intra-operative lymph node sampling and frozen section examination should be performed at the time of LapEn; when a malignancy is confirmed, oncologically appropriate lymph node dissection should be performed. PMID- 22321036 TI - Helicobacter pylori in Thai patients with cholangiocarcinoma and its association with biliary inflammation and proliferation. AB - OBJECTIVES: To investigate whether Helicobacter spp. infection and the cagA of H. pylori are associated with hepatobiliary pathology, specifically biliary inflammation, cell proliferation and cholangiocarcinoma (CCA). METHODS: Helicobacter species including H. pylori, H. bilis and H. hepaticus were detected in the specimens using the polymerase chain reaction (PCR). Biliary inflammation of the liver and gallbladders was semi-quantitatively graded on hematoxylin and eosin (H&E)-stained slides. Biliary proliferation was evaluated by immunohistochemistry using the Ki-67-labelling index. RESULTS: Helicobacter pylori was found in 66.7%, 41.5% and 25.0% of the patients in the CCA, cholelithiasis and control groups (P < 0.05), respectively. By comparison, H. bilis was found in 14.9% and 9.4% of the patients with CCA and cholelithiasis, respectively (P > 0.05), and was absent in the control group. The cagA gene of H. pylori was detected in 36.2% and 9.1% of the patients with CCA and cholelithiasis, respectively (P < 0.05). Among patients with CCA, cell inflammation and proliferation in the liver and gallbladder were significantly higher among those DNA H. pylori positive than negative. CONCLUSIONS: The present findings suggest that H. pylori, especially the cagA-positive strains, may be involved in the pathogenesis of hepatobiliary diseases, especially CCA through enhanced biliary cell inflammation and proliferation. PMID- 22321037 TI - Longterm outcome of photodynamic therapy compared with biliary stenting alone in patients with advanced hilar cholangiocarcinoma. AB - OBJECTIVES: This study aimed to determine longterm outcomes and factors associated with increased survival after photodynamic therapy (PDT) compared with endoscopic biliary drainage alone in patients presenting with advanced hilar cholangiocarcinoma (CC). METHODS: A retrospective analysis of the institutional database identifying all patients who presented with a diagnosis of hilar CC between December 1999 and January 2011 was conducted. RESULTS: Of the 232 patients identified, 72 (31%) were treated with PDT (Group A) and 71 (31%) were treated with endoscopic biliary drainage alone (Group B). Median survival was 9.8 months [95% confidence interval (CI) 7.42-12.25] in Group A and 7.3 months (95% CI 4.79-9.88) in Group B (P= 0.029). On multivariate analysis, biliary drainage without PDT (P= 0.025) and higher T-stage (P= 0.002) were significant predictors of shorter survival in all patients. In a subgroup analysis of patients in the PDT group, lower pre-PDT bilirubin level (P= 0.005), multiple PDT treatments (P= 0.044) and shortened time to treatment after diagnosis (P= 0.013) were significant predictors of improved survival. Median metal stent patency was longer in Group A than in Group B (215 days vs. 181 days; P= 0.018). CONCLUSIONS: Photodynamic therapy with stenting resulted in longer survival than stenting alone. Early PDT after diagnosis and multiple PDT treatments were shown to have survival benefits. Metal stent patency was longer in patients receiving PDT. Higher T-stage appears to be a predictor of early mortality in advanced bile duct cancer treated with PDT. PMID- 22321038 TI - Role of quantification of hepatic steatosis and future remnant volume in predicting hepatic dysfunction and complications after liver resection for colorectal metastases: a pilot study. AB - OBJECTIVES: Accurate prediction of safe remnant liver volume to minimize complications following liver resection remains challenging. The aim of this study was to assess whether quantification of steatosis improved the predictive value of preoperative volumetric analysis. METHODS: Thirty patients undergoing planned right or extended right hemi-hepatectomy for colorectal metastases were recruited prospectively. Magnetic resonance imaging was used to assess the level of hepatic steatosis and future remnant liver volume. These data were correlated with data on postoperative hepatic insufficiency, complications and hospital stay. Correlations of remnant percentage, remnant mass to patient mass and remnant mass to body surface area with and without steatosis measurements were assessed. RESULTS: In 10 of the 30 patients the planned liver resection was altered. Moderate-severe postoperative hepatic dysfunction was seen in 17 patients. Complications arose in 14 patients. The median level of steatosis was 3.8% (range: 1.2-17.6%), but was higher in patients (n= 10) who received preoperative chemotherapy (P= 0.124), in whom the median level was 4.8% (range: 1.5-17.6%). The strongest correlation was that of remnant liver mass to patient mass (r= 0.77, P < 0.001). However, the addition of steatosis quantification did not improve this correlation (r= 0.76, P < 0.001). CONCLUSIONS: This is the first study to combine volumetric with steatosis quantifications. No significant benefit was seen in this small pilot. However, these techniques may be useful in operative planning, particularly in patients receiving preoperative chemotherapy. PMID- 22321039 TI - Discharge disposition after pancreatic resection for malignancy: analysis of national trends. AB - OBJECTIVES: The aim of this study is to analyse national trends in discharge disposition following pancreatic resection for malignancy in the USA. METHODS: The Nationwide Inpatient Sample database was queried for 1993-2005 to identify patients who underwent pancreatic resection for malignancy. The status of patients at discharge (to home, home with home health care or to another facility) was noted. RESULTS: A weighted total of 51 866 patients who underwent pancreatectomy for malignant neoplasm of the pancreas were identified. Patients who died in the postoperative period and patients without a specified discharge disposition were excluded, leaving 43 603 patients for inclusion in the study. Overall mortality improved over the period of the study from 7.1% in 1993 to 5.2% in 2005. The number of patients discharged to another facility increased significantly from 5.5% in 1993 to 13.3% in 2005. Similarly, the number of patients discharged to home with home health assistance increased from 20.0% in 1993 to 33.0% in 2005. This corresponded with a statistically significant decrease in the number of patients discharged to home without assistance, from 74.5% in 1993 to 53.7% in 2005 (P= 0.002). CONCLUSIONS: The results of our study demonstrate that following pancreatic resection for malignancy, nearly half the patients will require some assistance after discharge. PMID- 22321040 TI - Surgical treatment of liver metastases of gastric cancer: is local treatment in a systemic disease worthwhile? AB - OBJECTIVES: The prognosis of patients with liver metastases of gastric cancer (LMGC) is dismal, but little is known about prognostic factors in these patients; thus justification for surgical resection is still controversial. The purpose of this study was to review recent outcomes of hepatectomy for LMGC and to determine which patients represent suitable candidates for surgery by assessing surgical results and clinicopathologic features. METHODS: Outcomes in 21 patients with LMGC who underwent hepatectomy between 1998 and 2007 were assessed. Isolated metastases and potential to perform a curative resection were requisite indi cations for surgery. Surgical outcome and clinicopathologic features of the hepatic metastases were analysed. RESULTS: Overall 1-, 3- and 5-year survival rates after hepatic resection were 68%, 31% and 19%, respectively; three patients survived for >5 years without recurrence. Univariate analysis revealed a solitary metastasis, negative margin (R0) resection and the presence of a peritumoral fibrous capsule as significant favourable prognostic factors. These characteristics were present in all of the three patients who survived for >5 years. CONCLUSIONS: Solitary metastases from gastric cancer should be treated surgically and confer a better prognosis. Surgical resection should provide microscopically negative margins (R0). A new prognostic factor, the presence of a pseudocapsule, may be associated with improved prognosis. PMID- 22321041 TI - Technical description of a regional lymphadenectomy in radical surgery for gallbladder cancer. AB - BACKGROUND: The guidelines for resection of gallbladder cancer include a regional lymphadenectomy; yet it is uncommonly performed in practice and inadequately described in the literature. The present study describes the technique of a regional lymphadenectomy for gallbladder cancer, as practiced by the author. METHODS/TECHNIQUE: After confirming resectability, the duodenum is kocherized. The dissection starts from the posterior aspects of the duodenum and head of the pancreas and extends superiorly to the retroportal area. This is followed by dissection of the common hepatic artery and its branches, the bile duct and the anterior aspect of the portal vein until the hepatic hilum. Resection of the gallbladder with an appropriate liver resection completes the surgery. RESULTS: This technique was used for a regional lymphadenectomy in 27 patients, of which 14 underwent radical cholecystectomy upfront, and 13 had revisional surgery for incidentally detected gallbladder cancer. The median number of lymph nodes dissected on histopathology was 8 (range 3 to 18). Eleven patients had metastatic lymph nodes on histopathological examination. There was no post-operative mortality. Two patients had a bile leak which resolved with conservative management. CONCLUSION: A systematic approach towards a regional lymphadenectomy ensures a consistent nodal harvest in patients undergoing radical resection for gallbladder cancer. PMID- 22321043 TI - Impact of the deepwater horizon oil spill on bioavailable polycyclic aromatic hydrocarbons in Gulf of Mexico coastal waters. AB - An estimated 4.1 million barrels of oil and 2.1 million gallons of dispersants were released into the Gulf of Mexico during the Deepwater Horizon oil spill. There is a continued need for information about the impacts and long-term effects of the disaster on the Gulf of Mexico. The objectives of this study were to assess bioavailable polycyclic aromatic hydrocarbons (PAHs) in the coastal waters of four Gulf Coast states that were impacted by the spill. For over a year, beginning in May 2010, passive sampling devices were used to monitor the bioavailable concentration of PAHs. Prior to shoreline oiling, baseline data were obtained at all the study sites, allowing for direct before and after comparisons of PAH contamination. Significant increases in bioavailable PAHs were seen following the oil spill, however, preoiling levels were observed at all sites by March 2011. A return to elevated PAH concentrations, accompanied by a chemical fingerprint similar to that observed while the site was being impacted by the spill, was observed in Alabama in summer 2011. Chemical forensic modeling demonstrated that elevated PAH concentrations are associated with distinctive chemical profiles. PMID- 22321044 TI - Flash flow pyrolysis: mimicking flash vacuum pyrolysis in a high-temperature/high pressure liquid-phase microreactor environment. AB - Flash vacuum pyrolysis (FVP) is a gas-phase continuous-flow technique where a substrate is sublimed through a hot quartz tube under high vacuum at temperatures of 400-1100 degrees C. Thermal activation occurs mainly by molecule-wall collisions with contact times in the region of milliseconds. As a preparative method, FVP is used mainly to induce intramolecular high-temperature transformations leading to products that cannot easily be obtained by other methods. It is demonstrated herein that liquid-phase high-temperature/high pressure (high-T/p) microreactor conditions (160-350 degrees C, 90-180 bar) employing near- or supercritical fluids as reaction media can mimic the results obtained using preparative gas-phase FVP protocols. The high-T/p liquid-phase "flash flow pyrolysis" (FFP) technique was applied to the thermolysis of Meldrum's acid derivatives, pyrrole-2,3-diones, and pyrrole-2-carboxylic esters, producing the expected target heterocycles in high yields with residence times between 10 s and 10 min. The exact control over flow rate (and thus residence time) using the liquid-phase FFP method allows a tuning of reaction selectivities not easily achievable using FVP. Since the solution-phase FFP method does not require the substrate to be volatile any more--a major limitation in classical FVP--the transformations become readily scalable, allowing higher productivities and space-time yields compared with gas-phase protocols. Differential scanning calorimetry measurements and extensive DFT calculations provided essential information on pyrolysis energy barriers and the involved reaction mechanisms. A correlation between computed activation energies and experimental gas-phase FVP (molecule-wall collisions) and liquid-phase FFP (molecule-molecule collisions) pyrolysis temperatures was derived. PMID- 22321045 TI - Women ending marriage to a problem drinking partner decrease their own risk for problem drinking. AB - AIMS: Marital dissolution is associated with increased risk of problematic drinking. However, marriage to a problem drinker also increases this risk, and ending this type of relationship may actually decrease risk of problematic drinking. This study tested whether women ending their marriage to a problem drinker exhibited improvements in drinking. DESIGN: National Epidemiologic Survey on Alcohol and Related Conditions, a two-wave nationally representative survey of the US adult population. SETTING: In-person interviews conducted in US households. PARTICIPANTS: Females married or living as if married at wave 1 at least 18 years of age. MEASUREMENTS: Socio-demographics, drinking frequency, drinking quantity, alcohol use disorders, problem drinking, partner problem drinking and relationship dissolution. FINDINGS: Ending marriage to a non problem drinker predicted increased frequency of drinking [risk ratio (RR) = 1.55; 95% confidence interval (CI) = 1.43, 1.67], heavier drinking (RR = 1.30; 95% CI = 1.71, 1.45), more problematic drinking (RR = 2.45; 95% CI = 2.17, 2.77) and a greater likelihood of use disorder diagnosis [odds ratio (OR) = 2.2; 95% CI = 1.67, 2.91]. Ending a relationship with a problem drinker predicted less frequent drinking (RR = 0.94; 95% CI = 0.90, 0.98), less heavy drinking (RR = 0.84; 95% CI = 0.78, 0.90) and fewer alcohol-related problems (RR = 0.77; 95% CI = 0.62, 0.95). CONCLUSIONS: Ending a marriage with a husband who drinks problematically may decrease risk of alcohol-related problems among women, substantiating the need for alcohol treatments to address a problem drinking partner. PMID- 22321046 TI - Frequent inactivation of the BAP1 gene in epithelioid-type malignant mesothelioma. AB - In the present study, we analyzed genomic alterations of BRCA1-associated protein 1 (BAP1) in 23 malignant mesotheliomas (MMs), 16 epithelioid and seven non epithelioid, consisting of 18 clinical specimens and five established cell lines. In examining these samples for homozygous deletions and sequence-level mutations, we found biallelic BAP1 gene alterations in 14 of 23 MMs (61%). Seven of these 14 MMs had homozygous deletions of the partial or entire BAP1 gene, another five had sequence-level mutations, including small deletions, a nonsense mutation, and missense mutations with additional monoallelic deletions, and the remaining two had homozygous mutations without allelic loss. All but one of the 14 BAP1 gene mutations were found in the epithelioid-type MMs; BAP1 mutations were found in 13 of 16 epithelioid-type MMs, but in only one of seven non-epithelioid-type MMs (13/16 vs 1/7; P = 0.005). There was no BAP1 mRNA expression in MMs with biallelic deletion and repressed expression was confirmed in MM specimens with deletion/mutation as compared with Met5a, SV40-transformed normal mesothelial cells. Western blot showed that seven of eight epithelioid MMs analyzed were BAP1 negative. Immunostaining with anti-BAP1 antibody in normal lung tissues revealed clear nuclear staining of normal mesothelial cells. No nuclear staining was observed among BAP1 mutation-positive MM tumors, whereas nuclear staining was observed among BAP1 mutation-negative MM tumors. These results suggest that the lack of the tumor suppressor BAP1 may be more specifically involved in the pathogenesis of epithelioid MM rather than non-epithelioid MM, and would be useful for diagnosis of epithelioid-type MM. PMID- 22321047 TI - Risk adjusted benchmarking of clinical anastomotic leakage rate after total mesorectal excision in the context of an improvement project. AB - AIM: Anastomotic leakage (AL) after total mesorectal excision (TME) is a major adverse event. This study evaluates variability in AL between centres participating on a voluntary basis in PROCARE, a Belgian improvement project, and how further improvement of the AL rate might be achieved. METHOD: Between January 2006 and March 2011, detailed data on 1815 patients (mean age 65.5 years, 63% male) who underwent elective TME with colo-anal reconstruction for rectal cancer were registered by 48 centres. Variability in early clinical AL rate was analysed before and after adjustment for gender, age > 60 years, American Society of Anesthesiologists score of 3 or more and body mass index > 25 kg/m(2). RESULTS: The overall AL rate was 6.7% (95% CI 5.6%-7.9%). Early AL required reoperation in 86.8% of patients. It increased length of hospital stay from 14.7 days to 32.4 days and in-hospital mortality from 1.1% to 4.8%. Statistically significant variability in AL rate between centres was not observed, either before or after risk adjustment. Nonetheless, further improvement may be achievable in some centres by targeting the adjusted performance of better performing centres. These centres used neoadjuvant treatment, rectal irrigation, mobilization of the splenic flexure, resection of the sigmoid colon, side-to-end colo-anastomosis with or without pouch and defunctioning stoma at primary surgery in a significantly higher proportion of patients than less well performing centres. CONCLUSION: The overall AL rate was low but needs to be interpreted with caution because of incomplete registration. Further improvement might be achieved by adopting the approach of better performing centres. PMID- 22321048 TI - Bcl-2 and BLIMP-1 expression predict worse prognosis in gastric diffuse large B cell lymphoma (DLCBL) while other markers for nodal DLBCL are not useful. AB - AIMS: Previous studies have identified clinicopathological and immunohistochemical differences among diffuse large B cell lymphomas (DLBCL) as a function of disease location. Nevertheless, there is a continuing tendency to generalize the prognostic value of various identified markers without taking into account tumour site. Accordingly, we analysed the prognostic value of several of the immunohistochemical markers that have been proposed for nodal DLBCL in a group of patients with gastric DLBCL. METHODS AND RESULTS: Using histochemical methods, CD10, Bcl-6, Gcet1, MUM-1, Bcl-2 and BLIMP-1 expression was investigated in 43 cases of gastric DBLCL. As in nodal DLBCLs, expression of BLIMP-1, and of Bcl-2 in non-germinal centre B cell-like (non-GCB) patients, was associated with a worse prognosis. However, unlike nodal DBLCL, there was no significant association of prognosis with expression of CD10, Bcl-6, Gcet1 or MUM-1, or with categorization according to Hans or Muris algorithms. CONCLUSIONS: Although most markers of prognosis in nodal DLBCL are not useful indicators for gastric DLBCL, Bcl-2 or BLIMP-1 expression does correlate with worse prognosis. These data support the notion that clinicopathological features in DLBCL vary according to the disease location. PMID- 22321049 TI - Age- and gender-specific population attributable risks of metabolic disorders on all-cause and cardiovascular mortality in Taiwan. AB - BACKGROUND: The extent of attributable risks of metabolic syndrome (MetS) and its components on mortality remains unclear, especially with respect to age and gender. We aimed to assess the age- and gender-specific population attributable risks (PARs) for cardiovascular disease (CVD)-related mortality and all-cause mortality for public health planning. METHODS: A total of 2,092 men and 2,197 women 30 years of age and older, who were included in the 2002 Taiwan Survey of Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH), were linked to national death certificates acquired through December 31, 2009. Cox proportional hazard models were used to calculate adjusted hazard ratios and PARs for mortality, with a median follow-up of 7.7 years. RESULTS: The respective PAR percentages of MetS for all-cause and CVD-related mortality were 11.6 and 39.2 in men, respectively, and 18.6 and 44.4 in women, respectively. Central obesity had the highest PAR for CVD mortality in women (57.5%), whereas arterial hypertension had the highest PAR in men (57.5%). For all-cause mortality, younger men and post-menopausal women had higher PARs related to Mets and its components; for CVD mortality, post menopausal women had higher overall PARs than their pre-menopausal counterparts. CONCLUSIONS: MetS has a limited application to the PAR for all-cause mortality, especially in men; its PAR for CVD mortality is more evident. For CVD mortality, MetS components have higher PARs than MetS itself, especially hypertension in men and waist circumference in post-menopausal women. In addition, PARs for diabetes mellitus and low HDL-cholesterol may exceed 20%. We suggest differential control of risk factors in different subpopulation as a strategy to prevent CVD-related mortality. PMID- 22321050 TI - Can a cocktail designed for phenotyping pharmacokinetics and metabolism enzymes in human be used efficiently in rat? AB - We recently designed the CIME cocktail consisting of 10 drugs to assess the activity of the major human CYPs (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A), a phase II enzyme (UGT1A1/6/9), two drug transporters (P-gp and OATP1B1) and a component of the renal function ( Videau et al. 2010 ). The present work aimed at studying the usefulness of the CIME cocktail in the rat.The CIME cocktail was given per os to three male and three female rats, or incubated with rat liver microsomes. Parent substrates and metabolites were quantified by LC MS/MS in plasma, urine and hepatic microsomal media, and phenotyping index were subsequently calculated.The CIME cocktail could therefore be used in the rat to phenotype rapidly and simultaneously CYP3A1/2 with omeprazole/omeprazole-sulfone, midazolam/1'-hydroxymidazolam or 4-hydroxymidazolam and/or dextromethorphan/3 methoxymorphinan, CYP2C6/11 with tolbutamide/4-hydroxytolbutamide, CYP2D1/2 with omeprazole/5-hydroxyomeprazole or dextromethorphan/dextrorphan, and UGT1A6/7 with acetaminophen/acetaminophen-glucuronide. Our results confirmed also several known gender differences and brought new information on the urinary excretion of rosuvastatin. However, the major rat CYPs, CYP2C11 and CYP2C12, are not specifically assessed. An optimized version of the CIME cocktail should therefore be designed and would be of major importance to more largely phenotype DMPK enzymes in rats to study DMPK variability factors such as disease, age, or to exposure to inductors or inhibitors. PMID- 22321051 TI - Significance of xenobiotic metabolism for bioaccumulation kinetics of organic chemicals in Gammarus pulex. AB - Bioaccumulation and biotransformation are key toxicokinetic processes that modify toxicity of chemicals and sensitivity of organisms. Bioaccumulation kinetics vary greatly among organisms and chemicals; thus, we investigated the influence of biotransformation kinetics on bioaccumulation in a model aquatic invertebrate using fifteen (14)C-labeled organic xenobiotics from diverse chemical classes and physicochemical properties (1,2,3-trichlorobenzene, imidacloprid, 4,6-dinitro-o cresol, ethylacrylate, malathion, chlorpyrifos, aldicarb, carbofuran, carbaryl, 2,4-dichlorophenol, 2,4,5-trichlorophenol, pentachlorophenol, 4-nitrobenzyl chloride, 2,4-dichloroaniline, and sea-nine (4,5-dichloro-2-octyl-3 isothiazolone)). We detected and identified metabolites using HPLC with UV and radio-detection as well as high resolution mass spectrometry (LTQ-Orbitrap). Kinetics of uptake, biotransformation, and elimination of parent compounds and metabolites were modeled with a first-order one-compartment model. Bioaccumulation factors were calculated for parent compounds and metabolite enrichment factors for metabolites. Out of 19 detected metabolites, we identified seven by standards or accurate mass measurements and two via pathway analysis and analogies to other compounds. 1,2,3-Trichlorobenzene, imidacloprid, and 4,6 dinitro-o-cresol were not biotransformed. Dietary uptake contributed little to overall uptake. Differentiation between parent and metabolites increased accuracy of bioaccumulation parameters compared to total (14)C measurements. Biotransformation dominated toxicokinetics and strongly affected internal concentrations of parent compounds and metabolites. Many metabolites reached higher internal concentrations than their parents, characterized by large metabolite enrichment factors. PMID- 22321052 TI - Rates and clinical correlates of treatment non-adherence in schizoaffective bipolar patients. AB - OBJECTIVE: To analyze demographical, clinical, and therapeutic variables that may be associated with pharmacological non-adherence in a sample of schizoaffective patients, bipolar type. METHOD: Adherence to treatment and its clinical correlates were assessed at the end of a 10-year follow-up in 76 patients meeting DSM-IV-TR diagnosis of schizoaffective disorder, bipolar type. Adherent and poorly adherent patients were compared regarding clinical and therapeutic variables. RESULTS: The rate of poorly adherent patients was 32/76 (41.2%) of the sample. Adherent patients were more likely to have presented an affective episode at illness onset and to have fewer purely - non-affective - psychotic episodes. Demographic or other clinical variables were not found to be associated to treatment adherence. Family history for psychiatric disorders or suicide did not correlate either, and neither did any specific pharmacological agent. CONCLUSION: Rates of non-adherence in schizoaffective disorder are high. Adherence seems to be associated to a more affective course of illness (affective first episode and fewer purely psychotic episodes). Patients with more prominent schizophrenia-like characteristics could be at higher risk for poor adherence and need to be closely followed and monitored. Even when properly treated, schizoaffective disorder is a disabling and severe disorder with high risk for recurrences. PMID- 22321053 TI - Factors associated with the avoidance of red blood cell transfusion after hematopoietic stem cell transplantation. AB - BACKGROUND: Red blood cell (RBC) transfusion is required frequently for most patients after hematopoietic stem cell transplantation (HSCT). RBC transfusion, however, can be associated with adverse events including transfusion reactions, acquiring transmissible disease, and delayed recovery. Factors associated with avoidance of transfusion are not well documented. STUDY DESIGN AND METHODS: Data concerning RBC transfusions between Day 0 and Day +30 were analyzed for patients undergoing HSCT at a single Canadian transplant center between January 2002 and December 2007. RESULTS: Of 555 patients undergoing HSCT with complete RBC transfusion data, 59 patients (10.6%) did not require RBC transfusion in the first 30 days after HSCT. Univariate analysis showed no significant difference in age, graft source, donor type, or conditioning regimen between transfused and nontransfused patients. Factors that were significantly associated with avoidance of transfusion included male sex (p = 0.0013), diagnosis, specifically plasma cell dyscrasias (p < 0.0001), early-stage disease (p = 0.006), and higher baseline hemoglobin (Hb) at time of transplant (p < 0.0001). In multivariate analysis, higher pretransplant Hb, male sex, and early-stage disease remained significantly associated with avoidance of RBC transfusion. Pretransplant Hb correlated inversely with the number of RBC transfusions (r = -0.89). CONCLUSION: Increased pretransplant Hb, male sex, and early-stage disease are associated with avoidance of RBC transfusion after HSCT. Interventions aimed at improving pretransplant Hb levels require further study. PMID- 22321055 TI - Can transplantation be zero risk? AB - Proposed CDC guideline designed to thwart HIV, HBV and HCV transmission in organ donation may severely restrict organ availability. PMID- 22321054 TI - Circulating lymphocyte subsets in different clinical situations after renal transplantation. AB - Phenotypic characterization of T and B lymphocytes allows the discrimination of functionally different subsets. Here, we questioned whether changes in peripheral lymphocyte subset distribution reflect specific clinical and histopathological entities after renal transplantation. Sixty-five renal transplant recipients with either histologically proven (sub)clinical acute rejection or chronic allograft dysfunction, or without abnormalities were studied for their peripheral lymphocyte subset composition and compared with 15 healthy control individuals. Naive, memory and effector CD8(+) T-cell counts were measured by staining for CD27, CD28 and CD45RO/RA. In addition, we studied the CD25(+) CD4(+) T-cell population for its composition regarding regulatory Foxp3(+) CD45RO(+) CD127(-) cells and activated CD45RO(+) CD127(+) cells. Naive, non-switched and switched memory B cells were defined by staining for IgD and CD27. We found a severe decrease in circulating effector-type CD8(+) T cells in recipients with chronic allograft dysfunction at 5 years after transplantation. Percentages of circulating CD25(+) CD127(low) CD4(+) regulatory T cells after transplantation were reduced, but we could not detect any change in the percentage of CD127(+) CD45RO(+) CD4(+) activated T cells in patients at any time or condition after renal transplantation. Regardless of clinical events, all renal transplant recipients showed decreased total B-cell counts and a more differentiated circulating B-cell pool than healthy individuals. The changes in lymphocyte subset distribution probably reflect the chronic antigenic stimulation that occurs in these transplant recipients. To determine the usefulness of lymphocyte subset-typing in clinical practice, large cohort studies are necessary. PMID- 22321056 TI - Evaluation of Pentacam-Scheimpflug imaging of anterior segment parameters in patients with pseudoexfoliation syndrome and pseudoexfoliative glaucoma. AB - BACKGROUND: The aim was to evaluate anterior segment parameters in patients with pseudoexfoliation syndrome (PXS) or pseudoexfoliative glaucoma (PXG) with the Pentacam-Scheimpflug imaging system. METHODS: Eighty eyes of 53 patients with PXS (Group 1), 80 eyes of 57 patients with PXG (Group 2) and 80 eyes of 45 control cases (Group 3) were included in the study. Anterior chamber depth, volume (ACV), angle (ACA) width, central corneal thickness (CCT), central 3.0, 5.0 and 7.0 mm corneal volumes and pupil diameters were compared between groups. RESULTS: Although anterior chamber depths in the PXG group were significantly lower than the control group (p < 0.05), there was no statistically significant difference between the PXS group and the control group in means of anterior chamber depth values (p > 0.05). There were no statistically significant differences among PXS, PXG and the control group in mean values of ACV, ACA width, CCT, pupil diameters and central 3.0, 5.0 and 7.0 mm corneal volume (p > 0.05). conclusions: The anterior chamber depths of PXG patients were lower than those of healthy individuals. Although the difference in anterior chamber depth between PXG patients and normal patients was statistically significant, this finding is unlikely to be of clinical significance. The anterior chamber depths of PXS patients were similar to those of healthy individuals. There were no significant differences in the means of ACV, ACA width, CCT, pupil diameter and corneal volume values on central 3.0, 5.0 and 7.0 mm among patients with PXS, PXG and healthy individuals. PMID- 22321057 TI - Highly potent antidiuretic antagonists: conformational studies of vasopressin analogues modified with 1-naphthylalanine enantiomers at position 2. AB - In this paper, we investigated the structure-activity relationship of two vasopressin analogues, [Cpa(1),(L-1-Nal)(2) ]AVP (I) and [Cpa(1),(D-Nal)(2) ]AVP (II) by NMR spectroscopy and molecular modeling. Both peptides exhibit antioxytocic and antipressor potency. Inversion of configuration of the residue at position 2 converted a weak antidiuretic agonist (peptide I) into a highly potent antidiuretic antagonist (peptide II). For this reason, the purpose of our study was to explain the causes of different interactions of the analogues with V(2) receptors. The results have shown that both analogues display the tendency to adopt beta-turns in the 1-4 and 2-5 fragments, which is characteristic of OT and V(1a) receptors antagonists. In addition, the [Cpa(1),(L-1-Nal)(2) ]AVP (I) shows the propensity to assume beta-turn at position 7,8, which is believed to enhance antidiuretic activity, although not being crucial for its appearance. Moreover, the C-terminal amide group seems to be crucial for signal transduction. Its high accessibility in [Cpa(1),(L-1-Nal)(2) ]AVP (I) in contrast to [Cpa(1),(D 1-Nal)(2) ]AVP (II), probably results in V(2) receptor activation. PMID- 22321058 TI - Potential of an Er:YAG laser in the removal of calcium hydroxide from root canals. AB - OBJECTIVE: The purpose of this study was to assess the calcium hydroxide (CH) removal potential of an Er:YAG laser in combination with ethylenediaminetetraacetic acid (EDTA) and sodium hypochlorite (NaOCl) irrigation. BACKGROUND DATA: Removal of the CH dressing prior to the root canal filling is mandatory, as its remnants may mechanically block the apical area of the root canal system and also have an effect on the texture, viscosity, working time, penetration, and adhesion of root canal sealers. However, the removal of CH from the canal space is challenging, because it should ideally be placed deep and densely, so that its biological effects can be exerted in close proximity to the appropriate tissues. METHODS: In this study, the mandibular premolar teeth were embedded in acrylic blocks and sectioned longitudinally through the canal, forming two halves following shaping of the root canals with ProTaper (Maillefer, Ballaigues, Switzerland) rotary instruments. The teeth were reassembled after standard grooves created onto canal walls were filled with CH. In group 1, conventional irrigation was performed with 10 mL of 17% EDTA and 10 mL of 5% NaOCl, and in goup 2, Er:YAG laser following conventional irrigation was performed. Images of the grooves taken before and after irrigation were scored and the Mann-Whitney U test was used to statistically evaluate the results. RESULTS: The percentage of CH score reduction was 46.30% in group 1 and 60.58% in group 2. No significant difference was found between two groups (p>0.05). CONCLUSIONS: The laser did not improve the removal of CH during conventional root canal irrigation performed with NaOCl and EDTA under the conditions of current study. PMID- 22321059 TI - Effect of laser phototherapy on the hyalinization following orthodontic tooth movement in rats. AB - OBJECTIVE: We aimed to assess histologic changes after the use of laser phototherapy (LPT) during induced tooth movement with 40 g/F on young adult male rats. BACKGROUND DATA: Hyalinization is a sterile necrosis at the pressure zone of the periodontal ligament observed during the initial stages of the orthodontic movement, and extensive hyaline areas might cause an important delay in the tooth movement. The use of LPT is considered an enhancement factor for bone repair, as it stimulates microcirculation as well as the cellular metabolism. MATERIALS AND METHODS: Thirty animals were divided into two groups (n=15), named according to the time of animal death (7, 13, and 19 days). Half of the animals in each group were subjected to irradiation with infrared (IR) laser (lambda790 nm, round shaped beam, 40 mW, continuous wave (CW), diameter=2 mm (0.0314 cm(2)), 1.273 W/cm(2), time=2*112 sec+1*275 sec (total time 499 sec), 2*142.6/4.48 J+1*350/11 J, 635.2 J/cm(2)/20 J/ session), during orthodontic movement, the other half were used as nonirradiated controls. After animal death, specimens were sectioned, processed, and stained with hematoxylin and eosin (HE) and Sirius Red, and were used for semi-quantitative histologic analysis by light microscopy. Data were statistically analyzed. RESULTS: We demonstrated that LPT positively affected an important aspect of dental movement; the hyalinization. In the present study, we found a significant reduced expression of hyalinization after 19 days. On irradiated subjects, hyalinization was increased at day 7 with significant reduction at day 13. CONCLUSIONS: It is possible to conclude that the use of laser light caused histologic alterations during the orthodontic movement characterized by increased formation of areas of hyalinization at early stages, and late reduction when compared to nonirradiated animals. PMID- 22321060 TI - A carbohydrate supply and demand model of vegetative growth: response to temperature and light. AB - Photosynthesis is the limiting factor in crop growth models, but metabolism may also limit growth. We hypothesize that, over a wide range of temperature, growth is the minimum of the supply of carbohydrate from photosynthesis, and the demand of carbohydrate to synthesize new tissue. Biosynthetic demand limits growth at cool temperatures and increases exponentially with temperature. Photosynthesis limits growth at warm temperatures and decreases with temperature. Observations of tomato seedlings were used to calibrate a model based on this hypothesis. Model predictions were tested with published data for growth and carbohydrate content of sunflower and wheat. The model qualitatively fitted the response of growth of tomato and sunflower to both cool and warm temperatures. The transition between demand and supply limitation occurred at warmer temperatures under higher light and faster photosynthesis. Modifications were required to predict the observed non-structural carbohydrate (NSC). Some NSC was observed at warm temperatures, where demand should exceed supply. It was defined as a required reserve. Less NSC was found at cool temperatures than predicted from the difference between supply and demand. This was explained for tomato and sunflower, by feedback inhibition of NSC on photosynthesis. This inhibition was much less in winter wheat. PMID- 22321061 TI - Effects of exemestane and tamoxifen on hormone levels within the Tamoxifen Exemestane Adjuvant Multicentre (TEAM) trial: results of a German substudy. AB - AIM: The aim of this study was to compare the effects of exemestane and tamoxifen on hormone levels in postmenopausal patients with hormone receptor-positive breast cancer within a Germany substudy of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. METHODS: Within the TEAM trial, patients were randomized to receive adjuvant treatment with exemestane for 5 years or tamoxifen for 2.5-3 years followed by exemestane for 2-2.5 years. Serum levels of testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH) and parathyroid hormone (PTH) intact were measured at screening and after 3, 6 and 12 months of treatment. RESULTS: Data on hormone levels were available from 63 patients in the tamoxifen arm and 68 patients in the exemestane arm. Treatment with exemestane resulted in decreases from baseline in SHBG and PTH-intact levels, and increases from baseline in testosterone, DHEAS and FSH levels. Tamoxifen treatment resulted in increases from baseline in SHBG and PTH-intact, whereas levels of testosterone and FSH decreased and DHEAS levels did not change. At all time points assessed, the absolute change from baseline was significantly different between tamoxifen and exemestane for testosterone, SHBG, FSH and PTH-intact (all p < 0.0001). CONCLUSIONS: Exemestane and tamoxifen had statistically significantly different effects on hormone levels, including testosterone, SHBG, FSH and PTH-intact. PMID- 22321062 TI - Aliskiren for the treatment of essential hypertension under real-life practice conditions: design and baseline data of the prospective 3A registry. AB - BACKGROUND: The renin-angiotensin system (RAS) is a key target for blood pressure control and for cardiovascular and renal protection. Aliskiren is the first-in class direct oral inhibitor of renin that controls the rate-limiting step in the RAS cascade. So far little is known about the use and efficacy of aliskiren in the treatment of essential hypertension under clinical practice conditions. METHODS: The 3A registry was an open, prospective cohort study (observational registry) of 14,988 patients in 899 offices throughout Germany. Consecutive patients were eligible for inclusion if their physician had decided to modify their antihypertensive therapy. This included treatment with aliskiren or an angiotensin converting enzyme inhibitor (ACE-I)/angiotensin receptor blocker (ARB) or agents not blocking the RAS, alone or on top of an existing drug regimen. RESULTS: Mean age of patients was 65 years, their mean body mass index was 28.2 kg/m(2) 53.5% were men, 36% working, 90% in statutory health insurance and 26% in any disease management programme. Patients in the aliskiren and the RAS groups compared with the non-RAS group were older, more often men, had a longer history of hypertension, and had a higher prevalence of comorbidities (diabetes, chronic heart failure, ischaemic heart disease, renal disease). Mean systolic, but not diastolic blood pressure was substantially higher in the aliskiren group (158/91 mmHg vs. 154/89 mmHg in ACE-I/ARB vs. 152/89 mmHg in non RAS). Mean number of antihypertensive drugs was higher in the aliskiren group compared with the other groups (3.0 drugs vs. 2.5 in ACE-I/ARB vs. 1.6 in non RAS; p < 0.0001). CONCLUSIONS: In this large cohort of outpatients with hypertension, aliskiren was used mainly in patients with more severe stages of hypertension and those with concomitant diseases such as diabetes mellitus and impaired renal function. The 3A registry will provide important information about the use and efficacy of aliskiren in a real-life setting. PMID- 22321063 TI - Nuclear import of exogenous FGF1 requires the ER-protein LRRC59 and the importins Kpnalpha1 and Kpnbeta1. AB - Fibroblast growth factor 1 (FGF1) taken up by cells into endocytic vesicles can be translocated across vesicular membranes into the cytosol and the nucleus where it has a growth regulatory activity. Previously, leucine-rich repeat containing 59 (LRRC59) was identified as an intracellular binding partner of FGF1, but its biological role remained unknown. Here, we show that LRRC59 is strictly required for nuclear import of exogenous FGF1. siRNA-mediated depletion of LRRC59 did not inhibit the translocation of FGF1 into cytosol, but blocked the nuclear import of FGF1. We also found that an nuclear localization sequence (NLS) in FGF1, Ran GTPase, karyopherin-alpha1 (Kpnalpha1), and Kpnbeta1 were required for nuclear import of FGF1. Nuclear import of exogenous FGF2, which depends on CEP57/Translokin, was independent of LRRC59, but was dependent on Kpnalpha1 and Kpnbeta1, while the nuclear import of FGF1 was independent of CEP57. LRRC59 is a membrane-anchored protein that localizes to the endoplasmic reticulum (ER) and the nuclear envelope (NE). We found that LRRC59 possesses NLS-like sequences in its cytosolic part that can mediate nuclear import of soluble LRRC59 variants, and that the localization of LRRC59 to the NE depends on Kpnbeta1. We propose that LRRC59 facilitates transport of cytosolic FGF1 through nuclear pores by interaction with Kpns and movement of LRRC59 along the ER and NE membranes. PMID- 22321064 TI - Microplastics in the marine environment: a review of the methods used for identification and quantification. AB - This review of 68 studies compares the methodologies used for the identification and quantification of microplastics from the marine environment. Three main sampling strategies were identified: selective, volume-reduced, and bulk sampling. Most sediment samples came from sandy beaches at the high tide line, and most seawater samples were taken at the sea surface using neuston nets. Four steps were distinguished during sample processing: density separation, filtration, sieving, and visual sorting of microplastics. Visual sorting was one of the most commonly used methods for the identification of microplastics (using type, shape, degradation stage, and color as criteria). Chemical and physical characteristics (e.g., specific density) were also used. The most reliable method to identify the chemical composition of microplastics is by infrared spectroscopy. Most studies reported that plastic fragments were polyethylene and polypropylene polymers. Units commonly used for abundance estimates are "items per m(2)" for sediment and sea surface studies and "items per m(3)" for water column studies. Mesh size of sieves and filters used during sampling or sample processing influence abundance estimates. Most studies reported two main size ranges of microplastics: (i) 500 MUm-5 mm, which are retained by a 500 MUm sieve/net, and (ii) 1-500 MUm, or fractions thereof that are retained on filters. We recommend that future programs of monitoring continue to distinguish these size fractions, but we suggest standardized sampling procedures which allow the spatiotemporal comparison of microplastic abundance across marine environments. PMID- 22321065 TI - Diffuse large B cell lymphoma with an interfollicular pattern of proliferation shows a favourable prognosis: a study of the Osaka Lymphoma Study Group. AB - AIMS: Diffuse large B cell lymphoma (DLBCL) occasionally shows an interfollicular pattern of proliferation (DLBCL-IF) preserving lymphoid follicles. In this study, clinicopathological findings in 31 cases of DLBCL-IF were analysed. METHODS AND RESULTS: The study group comprised 20 males and 11 females, with ages ranging from 41 to 87 (median 69) years. The primary site was lymph node in 25 cases, and unknown in six due to advanced stage at diagnosis. Eight cases were clinical Stage I, 10 were Stage II, four Stage III, and nine Stage IV. A polymorphous pattern of proliferation containing large B cells and inflammatory cells was found in about 60% of cases. The overall survival rate of the DLBCL-IF patients was better than that of a DLBCL control group (log-rank test; P < 0.05). Multivariate analysis revealed that an interfollicular pattern of proliferation showed marginal significance for favourable prognosis (P = 0.069). Immunohistochemical double staining with antibodies for HLA-DR/CD68 (markers for M1-tumour-associated macrophage [M1-TAM]) or CD163/CD68 (M2-TAM) revealed that all DLBCL-IF patients with a low M2 count were alive at the end of observation. CONCLUSIONS: These findings suggest that DLBCL-IF is a clinicopathological entity distinct from ordinary DLBCL. The possible origin of tumour cells in DLBCL-IF from marginal zone B cells is discussed. PMID- 22321066 TI - Profiling of adhesive properties of the agglutinin-like sequence (ALS) protein family, a virulent attribute of Candida albicans. AB - Candida albicans is normally present in nearly all humans but can cause fatal diseases in immunocompromised patients. The agglutinin-like sequence (ALS) gene family of C. albicans has been suggested to be important for biofilm formation on medical devices. Here, we cloned all ALS genes and determined the binding properties of their gene products by cell surface engineering of Saccharomyces cerevisiae. Most of the ALS homologues had the ability to bind polypropylene, borosilicate glass and polyvinyl chloride, which are often used as materials in medical devices. However, ALS homologues were not able to bind polyurethane, polymethyl methacrylate, polytetrafluoroethylene or titanium. These findings will aid in the development of biofilm-resistant medical devices. PMID- 22321067 TI - Immunological evaluation of personalized peptide vaccination in refractory small cell lung cancer. AB - Since the prognosis of small cell lung cancer (SCLC) remains poor, development of new therapeutic approaches, including immunotherapies, would be desirable. In the current study, to evaluate immunological responses in refractory SCLC patients, we conducted a small scale phase II clinical trial of personalized peptide vaccination (PPV), in which vaccine antigens are selected based on pre-existing host immunity. Ten refractory SCLC patients, who had failed to respond to chemo- and/or chemoradiotherapies (median number of regimens, 2.5; median duration, 20.5 months), were enrolled. A maximum of four human leukocyte antigen (HLA)-matched peptides showing higher antigen-specific humoral responses were subcutaneously administered (weekly for six consecutive weeks and then bi-weekly thereafter). PPV was terminated before the 3rd administration in four patients because of rapid disease progression, whereas the remaining six patients completed at least one cycle (six times) of vaccinations. Peptide-specific immunological boosting was observed in all of the six patients at the end of the first cycle of vaccinations, with their survival time of 25, 24.5 (alive), 10 (alive), 9.5, 6.5, and 6 months. Number of previous chemotherapy regimens and frequency of CD3(+) CD26(+) cells in peripheral blood were potentially prognostic in the vaccinated patients (hazard ratio [HR] = 2.540, 95% confidence interval [CI] = 1.188-5.431, P = 0.016; HR = 0.941, 95% CI = 0.878-1.008, P = 0.084; respectively). Based on the feasible immune responses in refractory SCLC patients who received at least one cycle (six times) of vaccinations, PPV could be recommended for a next stage of larger-scale, prospective clinical trials. PMID- 22321068 TI - Actinomycosis of rectum: a bizarre complication of mesh rectopexy. PMID- 22321069 TI - Proteomic characterization of ovarian cancers identifying annexin-A4, phosphoserine aminotransferase, cellular retinoic acid-binding protein 2, and serpin B5 as histology-specific biomarkers. AB - Numerous studies have suggested that the different histological subtypes of ovarian carcinoma (i.e. clear cell, endometrioid, mucinous, and serous) have distinct clinical histories and characteristics; however, most studies that have aimed to determine biomarker have not performed comprehensive analyses based on subtype specificity. In the present study, we performed two-dimensional gel electrophoresis-based differential proteomic analysis of the different histological subtypes of ovarian carcinoma using tissue specimens from 39 patients. Seventy-seven protein spots (55 unique proteins) were found to be up- or downregulated in a subtype-specific manner. The most significant difference was observed for: (i) annexin-A4 (ANXA4) and phosphoserine aminotransferase (PSAT1), which are expressed strongly in clear cell carcinoma; (ii) cellular retinoic acid-binding protein 2 (CRABP2), which is expressed specifically in serous carcinoma; and (iii) serpin B5 (SPB5), which is upregulated in mucinous carcinoma. Validation of these candidates by western blotting using a 34 additional test sample set resulted in an expression pattern that was consistent with the screening and revealed that differential expression was independent of cancer stage or tumor grade within each subtype. Thus, the present study reinforces the notion that ovarian cancer subtypes can be clearly delineated on a molecular basis into four histopathological groups, and we propose that ANXA4, PSAT1, CRABP2, and SPB5 are candidate subtype-specific biomarkers that can help define the basis of tumor histology at a molecular level. PMID- 22321070 TI - Neural circuit competition in cocaine-seeking: roles of the infralimbic cortex and nucleus accumbens shell. AB - Following cocaine self-administration and extinction training, activity in the infralimbic cortex (IL) suppresses cocaine-seeking behavior. IL inactivation induces cocaine-seeking whereas activation suppresses cocaine-reinstated drug seeking. We asked how the suppression of cocaine-seeking induced by IL activation integrates with the circuitry promoting reinstated cocaine-seeking. Following cocaine self-administration and extinction training, rats underwent cue-induced reinstatement. In order to activate IL projections, microinjections of PEPA, a positive allosteric modulator of AMPA receptors, were made into the IL in combination with microinjections into a variety of nuclei known to regulate cocaine-seeking. Intra-IL PEPA administration suppressed cue-induced reinstatement without affecting locomotor activity. The suppression of cocaine seeking was reversed by activating dopamine neurons in the ventral tegmental area with microinjections of the MU-opioid receptor agonist DAMGO, and was partially reversed by dopamine microinjections into the prelimbic cortex or basolateral amygdala. Previous evidence suggests that the nucleus accumbens shell both promotes and suppresses cocaine-seeking. The suppression of cue-induced cocaine seeking by PEPA in the IL was reversed by intra-shell microinjections of either dopamine or the AMPA receptor antagonist CNQX, suggesting that the accumbens shell bidirectionally regulates cocaine-seeking depending on whether dopamine input is mimicked or glutamate input is inhibited. Together, these findings indicate that the IL acts 'upstream' from structures promoting cocaine-seeking, including from the mesolimbic dopamine projections to the prelimbic cortex and basolateral amygdala, and that the accumbens shell may be a crucial point of integration between the circuits that promote (ventral tegmental area) and inhibit (IL) reinstated cocaine-seeking. PMID- 22321071 TI - Stressing schizotypy: the modulating role of stress-relieving behaviours and intellectual capacity on functional hemispheric asymmetry. AB - Relative cognitive impairments are common along the schizophrenia spectrum reflecting potential psychopathological markers. Yet stress, a vulnerability marker in schizophrenia (including its spectrum), is likewise related to cognitive impairments. We investigated whether one such cognitive marker (attenuated functional hemispheric asymmetry) during stressful life periods might be linked to individuals' schizotypal features or rather to individuals' stress related experiences and behaviours. A total of 58 students performed a left hemisphere dominant (lateralised lexical decisions) and right hemisphere dominant (sex decisions on composite faces) task. In order to account for individual differences in stress sensitivity we separated participants into groups of high or low cognitive reserve according to their average current marks. In addition, participants filled in questionnaires on schizotypy (short O-LIFE), perceived stress, stress response, and a newly adapted questionnaire that enquired about potential stress compensation behaviour (elevated substance use). The most important finding was that enhanced substance use and cognitive disorganisation contributed to a right and left hemisphere shift in language dominance, respectively. We discuss that (i) former reports on right hemisphere shifts in language dominance with positive schizotypy might be explained by an associated higher substance use and (ii) cognitive disorganisation relates to unstable cognitive functioning that depend on individuals' life circumstances, contributing to published reports on inconsistent laterality-schizotypy relationships. PMID- 22321072 TI - Correlation of improved hepatitis B surface antigen detection limits with hepatitis B virus DNA nucleic acid test yield in blood donations. AB - BACKGROUND: This study provides data on the quantitative relationship between hepatitis B surface antigen (HBsAg; ng/mL) and hepatitis B virus (HBV) nucleic acid test (NAT; copies/mL) and addresses whether HBsAg assays with improved sensitivity would impact the detection of HBV-positive samples from occult or early seroconversion window period infections. STUDY DESIGN AND METHODS: Plasma samples were tested with an HBsAg assay (PRISM, Abbott Laboratories; sensitivity, 0.08-0.1 ng/mL) and with two HBsAg research prototype assays: HBsAg Prototype 1 (sensitivity, 0.032-0.045 ng/mL) and HBsAg Prototype 2 (sensitivity, 0.009-0.017 ng/mL); NAT assays were used to determine HBV DNA copy levels. RESULTS: Samples from 10 hepatitis B seroconversion panels covering the ramp-up phase were utilized to examine the relationship between detection of HBsAg using improved assays and viral load using quantitative HBV DNA polymerase chain reaction. For these samples, detection at the HBsAg assay cutoff (sample-to-cutoff ratio, 1.0) corresponded to 206 copies/mL HBV DNA for the HBsAg Prototype 1 assay and 329 copies/mL for the PRISM HBsAg assay. Compared to the PRISM HBsAg and HBsAg Prototype 1 assays, the HBsAg Prototype 2 assay detected two additional samples of 32 HBV DNA-positive samples obtained from blood donors with occult HBV and one of seven from blood donors with early window period infections. CONCLUSION: Increased sensitivity HBsAg assays result in the detection of samples containing lower viral loads. Improvements in the analytic sensitivity of HBsAg prototype assays allow the detection of additional HBV DNA-positive samples from donors with window period or occult infections compared to PRISM HBsAg. Improved HBsAg assays should allow for incremental detection of HBV infection. PMID- 22321073 TI - Extubation of the difficult airway--an important but neglected topic. PMID- 22321074 TI - Monitoring the brain in cardiac surgery--an evolving area for research. PMID- 22321075 TI - What is simulation for? PMID- 22321076 TI - A randomised, controlled trial comparing the AirtraqTM optical laryngoscope with conventional laryngoscopy in infants and children. AB - The Airtraq(TM) optical laryngoscope became available in paediatric sizes in the UK in May 2008. We conducted a randomised, controlled trial comparing the Airtraq with conventional laryngoscopy during routine anaesthesia in children. We hypothesised that the Airtraq laryngoscope would perform as well as conventional laryngoscopy. Sixty patients (20 infants and 40 children) were recruited. The mean (SD) intubation time using the Airtraq was longer than conventional laryngoscopy overall (47.3 (32.6) vs 26.3 (11.5) s; p=0.002), though the difference was only significant for children (p=0.003) and not for infants (p=0.29). The Airtraq provided a better view of the larynx compared with conventional laryngoscopy (in infants (percentage of glottic opening scores 100 (95-100 [90-100]) vs 77 (50-90 [40-100]), respectively; p=0.001; visual analogue scores for field of view 9.2 (9.2-9.5 [8.2-10.0]) vs 6.8 (5.1-8.0 [4.7-10.0]), respectively; p=0.001). In children, the Airtraq provided a similar view of the larynx (percentage of glottic opening scores 100 (100-100 [40-100]) vs 100 (90 100 [50-100]), respectively; visual analogue scores for field of view 9.2 (8.6 10.0 [7.0-10.0]) vs 9.2 (8.6-10.0 [5.6-10.0]), respectively; both p>0.05), compared with conventional laryngoscopy. PMID- 22321077 TI - Awake videolaryngoscopy-assisted tracheal intubation of the morbidly obese. AB - Awake videolaryngoscopy may be useful for the tracheal intubation of the morbidly obese. This prospective, observational study enrolled 50 patients undergoing bariatric surgery. After sedation and topical anaesthesia of the airway, awake tracheal intubation was attempted, assisted by videolaryngoscopy, and terminated if there was severe gagging, coughing, or inadequate laryngeal view. After three attempts the procedure was considered a failure. Twenty-seven intubations were successful on the first attempt, fifteen on the second, six on the third and two were not successful, giving a success rate of 96% (95% CI 86-100%). In one failure, inserting the tracheal tube caused severe gagging in spite of an adequate view of the larynx, and the trachea was intubated with the videolaryngoscope after induction of anaesthesia. The second failure was due to gagging, with subsequent tracheal intubation successful using fibreoptic bronchoscopy. When managing the morbidly obese airway, awake tracheal intubation using videolaryngoscopy may be considered. PMID- 22321078 TI - The precision of PiCCO(r) measurements in hypothermic post-cardiac arrest patients. AB - The aim of the present study was to determine the precision of the PiCCO((r)) system for post-cardiac arrest patients who underwent therapeutic hypothermia. The precision of the measurements for cardiac output, global end-diastolic volume, extravascular lung water and the pulmonary vascular permeability index was assessed using the least significant change; this was regarded as precise when less than 15%. A total of 462 measurement sets were prospectively performed on 88 patients following successful resuscitation after cardiac arrest. Using the mean value of three injections for a measurement, the least significant change for the cardiac output, global end-diastolic volume, extravascular lung water and pulmonary vascular permeability index measurements were found to be 7.8%, 8.5%, 7.8% and 12.1%, respectively. No significant differences between hypothermia (n=150) and non-hypothermia (n=312) were found. The PiCCO-derived variables were found to be precise for post-cardiac arrest patients even under conditions of varying body temperature. PMID- 22321079 TI - Effect of forced-air warming on the performance of operating theatre laminar flow ventilation. AB - Forced-air warming exhaust may disrupt operating theatre airflows via formation of convection currents, which depends upon differences in exhaust and operating room air temperatures. We investigated whether the floor-to-ceiling temperatures around a draped manikin in a laminar-flow theatre differed when using three types of warming devices: a forced-air warming blanket (Bair HuggerTM); an over-body conductive blanket (Hot DogTM); and an under-body resistive mattress (IndithermTM). With forced-air warming, mean (SD) temperatures were significantly elevated over the surgical site vs those measured with the conductive blanket (+2.73 (0.7) degrees C; p<0.001) or resistive mattress (+3.63 (0.7) degrees C; p<0.001). Air temperature differences were insignificant between devices at floor (p=0.339), knee (p=0.799) and head height levels (p=0.573). We conclude that forced-air warming generates convection current activity in the vicinity of the surgical site. The clinical concern is that these currents may disrupt ventilation airflows intended to clear airborne contaminants from the surgical site. PMID- 22321080 TI - Placement of coiled catheters into the paravertebral space. AB - There are conflicting results with regard to the use of catheter-based techniques for continuous paravertebral block. Local anaesthetic spread within the paravertebral space is limited and the clinical effect is often variable. Discrepancies between needle tip position and final catheter position can also be problematic. The aim of this proof-of-concept study was to assess the reliability of placing a newly developed coiled catheter in human cadavers. Sixty Tuohy needles and coiled catheters were placed under ultrasound guidance, three on each side of the thoracic vertebral column in 10 human cadavers. Computed tomography was used to assess needle tip and catheter tip locations. No catheter was misplaced into the epidural, pleural or prevertebral spaces. The mean (SD) distance between catheter tips and needle tips was 8.2 (4.9) mm. The median (IQR [range]) caudo-cephalad spread of contrast dye injectate through a subset of 20 catheters was 4 (4-5[3-8]) thoracic segments. All catheters were removed without incident. Precise paravertebral catheter placement can be achieved using ultrasound-guided placement of a coiled catheter. PMID- 22321081 TI - The effect of nitrous oxide on intra-ocular pressure in healthy adults. AB - Many anaesthetic agents affect intra-ocular pressure, yet little is known about nitrous oxide and intra-ocular pressure. This study assessed the effect of nitrous oxide on intra-ocular pressure in 20 healthy adult volunteers. The intra ocular pressure was measured at baseline, while breathing a 70:30 mix of nitrous oxide and oxygen for 12 min, and then while breathing room air for 15 min. A linear mixed effects model was used to assess change in intra-ocular pressure over time. There was no significant difference in intra-ocular pressure between baseline and during or after nitrous oxide inhalation. Several differences in intra-ocular pressure were noted between internal time-points: pressure increased by 2.4 mmHg between 3 and 6 min of breathing nitrous oxide (p=0.01); it increased by 1.4 mmHg between 3 and 9 min of breathing nitrous oxide (p=0.046); and it decreased by 2.2 mmHg between 6 min of breathing nitrous oxide and 15 min of breathing room air (p=0.035). This study indicates that nitrous oxide inhalation does not significantly change intra-ocular pressure from baseline values in a population of healthy adults. PMID- 22321082 TI - Tracheal intubation in morbidly obese patients: a comparison of the Intubating Laryngeal Mask AirwayTM and Laryngeal Mask Airway CTrachTM. AB - The aim of this study was to evaluate the efficacy of the Intubating Laryngeal Mask AirwayTM (ILMA) and Laryngeal Mask Airway CTrachTM (LMA CTrach) in facilitating tracheal intubation in morbidly obese patients. Eighty patients (body mass index >40 kg x m(-2)) were randomly allocated to the ILMA or the LMA CTrach. The median (IQR [range]) total time taken for tracheal intubation was shorter with the ILMA than with the LMA CTrach (78 (63-105 [40-265]) s vs 128 (98 221 [60-423]) s, respectively; p<0.001). Significantly more manoeuvres were applied for the satisfactory ventilation and viewing of the glottis with the LMA CTrach (25% vs 55% with the ILMA; p=0.006). During the postoperative period, there was more sore throat with the LMA CTrach (p<0.02). We conclude that the ILMA results in shorter intubation times with fewer manoeuvres and sore throat compared with the LMA CTrach in the morbidly obese. PMID- 22321083 TI - The role of sugammadex in the development and modification of an allergic response to rocuronium: evidence from a cutaneous model. AB - The availability of sugammadex as a selective encapsulating agent for rocuronium has led to speculation that it may be useful in mitigating rocuronium-induced anaphylaxis. Off-label use of sugammadex for this indication has already been documented in case reports although there are theoretical objections to the likelihood of an allergen-binding agent's being able to attenuate the immunological cascade of anaphylaxis. Using a cutaneous model of anaphylaxis in rocuronium-sensitised patients, we were unable to demonstrate that sugammadex was effective in attenuating the type-1 hypersensitivity reaction after it has been triggered by rocuronium, but we were able to demonstrate that these patients are anergic to sugammadex-bound rocuronium. These findings demonstrate that a cyclodextrin can bind an allergen and exclude it from interacting with the immune system, and may potentially lead to novel applications in other allergic diseases. However, there is no evidence that sugammadex should be used for the treatment of rocuronium-induced anaphylaxis, and clinical management should follow established protocols. PMID- 22321084 TI - Ability of non-invasive intermittent blood pressure monitoring and a continuous non-invasive arterial pressure monitor (CNAPTM) to provide new readings in each 1 min interval during elective caesarean section under spinal anaesthesia. AB - We compared the ability of automated non-invasive intermittent oscillometric blood pressure monitoring with a new device, CNAP(TM) (continuous non-invasive arterial pressure) to provide a new blood pressure reading in each 1-min interval between spinal anaesthesia and delivery during caesarean section. We also compared the accuracy of continuous non-invasive arterial pressure readings with non-invasive blood pressure measurements before spinal anaesthesia. Fifty-nine women participated. The non-invasive and continuous non-invasive monitors displayed new blood pressure readings in a mean of 82% (11%) and 83% (13%) (p = 0.97) of the one-minute intervals between spinal anaesthesia and delivery, respectively. Continuous non-invasive arterial pressure was more likely to fail on two or more consecutive minutes (p=0.001). From the pre-spinal readings, the mean bias, defined as non-invasive-continuous non-invasive arterial pressure, and limits of agreement (+/-2SD mean bias) for systolic, diastolic and mean blood pressure respectively were +1.3 (+/-26.0), -2.9 (+/-21.8) and +2.6 (+/-20.4) mmHg. The new monitor has disadvantages compared with conventional non-invasive intermittent blood pressure monitoring. PMID- 22321085 TI - A review of postoperative cognitive dysfunction and neuroinflammation associated with cardiac surgery and anaesthesia. AB - Postoperative cognitive dysfunction is receiving increasing attention, particularly as it mainly affects the (growing) elderly population. Until recently, cognitive deficits after cardiac surgery were thought to be caused by physiological disturbances associated with the cardiopulmonary bypass technique. Although the technique of 'off-pump' coronary revascularisation may potentially be associated with improved outcome, long-term follow-up studies have failed to demonstrate a significant reduction in the incidence of postoperative cognitive dysfunction. The focus of research is thus shifting from cardiopulmonary bypass to other factors common to both techniques, such as surgery, anaesthesia and patient-related predisposing factors. Priming of the immune system by ageing and atherosclerosis may result in an exaggerated systemic and cerebral inflammatory response to cardiac surgery and anaesthesia, causing neuronal loss or dysfunction resulting in cognitive dysfunction. We briefly discuss the evidence for cardiopulmonary bypass-related neuronal injuries in adult cardiac surgery patients, and review the evidence that immune priming is a key factor in the pathogenesis of cognitive dysfunction after cardiac surgery. PMID- 22321086 TI - Anaphylaxis to levobupivacaine--probably not. PMID- 22321087 TI - Anaphylaxis to levobupivacaine? Maybe.... PMID- 22321089 TI - In vitro performance of a new non-invasive extracorporeal saturation monitor. PMID- 22321091 TI - The correct dosing regimen for sugammadex in morbidly obese patients. PMID- 22321092 TI - Ethylene glycol poisoning and the lactate gap. PMID- 22321093 TI - Atropine and ephedrine: a significant waste in the operating theatre. PMID- 22321094 TI - Use of ultrasound to assess superior and recurrent laryngeal nerve function immediately after thyroid surgery. PMID- 22321095 TI - Postoperative hypothermia and outcomes after cardiac surgery. PMID- 22321096 TI - Is it good to share? Suction splitters in operating theatres. PMID- 22321097 TI - Anaphylaxis to dye during breast surgery. PMID- 22321099 TI - Failure of glass prefilled syringe. PMID- 22321101 TI - EpifuseTM failure causing epidural disconnection. PMID- 22321102 TI - Portex EpifuseTM connector blockages. PMID- 22321103 TI - Occluded Portex EpifuseTM epidural connector. PMID- 22321104 TI - Difficult Airway Society Guidelines for the management of tracheal extubation. AB - Tracheal extubation is a high-risk phase of anaesthesia. The majority of problems that occur during extubation and emergence are of a minor nature, but a small and significant number may result in injury or death. The need for a strategy incorporating extubation is mentioned in several international airway management guidelines, but the subject is not discussed in detail, and the emphasis has been on extubation of the patient with a difficult airway. The Difficult Airway Society has developed guidelines for the safe management of tracheal extubation in adult peri-operative practice. The guidelines discuss the problems arising during extubation and recovery and promote a strategic, stepwise approach to extubation. They emphasise the importance of planning and preparation, and include practical techniques for use in clinical practice and recommendations for post-extubation care. PMID- 22321105 TI - Sex-biased genetic component distribution among populations: additive genetic and maternal contributions to phenotypic differences among populations of Chinook salmon. AB - An approach frequently used to demonstrate a genetic basis for population-level phenotypic differences is to employ common garden rearing designs, where observed differences are assumed to be attributable to primarily additive genetic effects. Here, in two common garden experiments, we employed factorial breeding designs between wild and domestic, and among wild populations of Chinook salmon (Oncorhynchus tshawytscha). We measured the contribution of additive (V(A)) and maternal (V(M)) effects to the observed population differences for 17 life history and fitness-related traits. Our results show that, in general, maternal effects contribute more to phenotypic differences among populations than additive genetic effects. These results suggest that maternal effects are important in population phenotypic differentiation and also signify that the inclusion of the maternal source of variation is critical when employing models to test population differences in salmon, such as in local adaptation studies. PMID- 22321106 TI - Transcription factor network regulating CD(+)CD8(+) thymocyte survival. AB - More than 80% of thymocytes are CD4(+)CD8(+) double positive (DP) cells subject to positive/ negative selection. The lifespan of DP thymocytes is critical in shaping the peripheral T-cell repertoire essential for mounting immune responses against foreign, but not self, antigens. During T-cell maturation, if the first round of T-cell receptor (TCR) alpha chain rearrangement fails to generate a productive T-cell receptor, DP cells start another round of alpha chain rearrangement until positive selection or cell death intervenes. Thus, the lifespan of DP cells determines how many rounds of alpha chain rearrangement can be carried out, and influences the likelihood of completing positive selection. The antiapoptotic protein Bcl-x(L) is the ultimate effector regulating DP cell survival, and several transcription factors critical for T-cell development, such as TCF-1, E proteins, c-Myb, and RORgammat, regulate DP survival via a Bcl-x(L) dependent pathway. However, the relationship between these transcription factors in this process is largely unclear. Recent results are revealing an interactive network among these critical factors during regulation of DP thymocyte survival. This review will discuss how these transcription factors potentially work together to control DP thymocyte survival that is critical for successful completion of T-cell development. PMID- 22321107 TI - Induction and function of IFNbeta during viral and bacterial infection. AB - Since the discovery of the protein "interferon" over 50 years ago, IFNbeta, an antiviral cytokine, has been well studied. In particular, the pathways inducing this cytokine during viral infection have been characterized, leading to the discovery of a multitude of pattern recognition receptors. IFNbeta is also induced during bacterial infection, following recognition of bacterial ligands by the host viral and DNA sensors. However, the function of IFNbeta during bacterial infection is variable and sometimes detrimental to the host. This review discusses the currently identified receptors and pathways engaged in IFNbeta induction during infection, with emphasis on the role of IFNbeta during bacterial infection. PMID- 22321109 TI - Phytochemical composition, anti-inflammatory, and antiproliferative activity of whole wheat flour. AB - Whole wheat flour from five wheat cultivars was evaluated for phenolic, carotenoid, and tocopherol compositions as well as anti-inflammatory and antiproliferative activities against HT-29 cells. The total ferulic acid content ranged from 452 to 731 MUg/g among the five cultivars and was primarily present in the insoluble-bound form. Lutein was the only carotenoid detected and ranged from 1.5 to 4.0 MUg/g, and alpha-tocopherol levels ranged from 12 to 61 MUg/g. Extracts of four cultivars demonstrated significant anti-inflammatory activity, measured as inhibition of interleukin-1beta (IL-1beta) mRNA expression; however, none of the extracts inhibited tumor necrosis factor-alpha (TNF-alpha) mRNA expression, a second indicator of anti-inflammatory activity. Proliferation of HT 29 adenocarcinoma cells was inhibited by extracts from all cultivars at the dose of 100 mg botanical equivalent/mL. The cultivar WestBred 936 had the greatest antiproliferative activity at lower concentrations (20 and 50 mg botanical equivalent/mL), had the greatest anti-inflammatory effect against IL-1beta, and also had the highest levels of ferulic acid and alpha-tocopherol. This research shows that whole wheat flours of these five cultivars varied significantly in their contents of phenolics, carotenoids, and alpha-tocopherol as well as in their anti-inflammatory and antiproliferative potentials, suggesting the possibility that wheat varieties can be selected based on potential health benefits. PMID- 22321110 TI - Influence of systemic lupus erythematosus on procedure selection and outcomes of patients undergoing isolated mitral valve surgery. AB - BACKGROUND: Cardiovascular disease is the main cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). SLE as a risk factor for adverse outcomes during mitral surgery has not been studied. The purpose of this investigation was to compare procedure selection and outcomes of patients with and without SLE. METHODS: The 2005-2008 Nationwide Inpatient Sample database was searched to identify patients >=18 years of age undergoing isolated mitral repair or replacement. Patients with and without SLE were compared on baseline characteristics and hospital outcomes. Within patients with SLE, those undergoing repair and replacement were compared. RESULTS: SLE patients comprised 0.9% (620/70,969) of the isolated mitral valve surgery population. Patients with SLE were significantly younger, more likely to be female, less likely to be white, had higher Charlson comorbidity index, and less often presented electively. Patients with SLE had a higher incidence of prolonged hospitalization (LOS > 10 days; 44.4% vs. 34.7%, p = 0.0392). Mortality was similar for patients with and without SLE undergoing isolated mitral valve surgery (OR = 0.76, 95% CI 0.28 2.05, p = 0.5821). Patients with SLE were less likely to have mitral valve repair (27.1% vs. 45.6%, p = 0.0002). Baseline characteristics were similar between SLE repair and replacement subsets. Median LOS was higher for replacement (10 days vs. 7 days, p = 0.0014). Hospital mortality was 0% for SLE mitral repair patients and <4.0% for SLE replacement patients. CONCLUSIONS: Patients with SLE present for isolated mitral valve surgery at a much younger age and with worse preoperative profiles. Although mitral repair rates were lower in patients with SLE, hospital outcomes were excellent, and comparable to those of patients without SLE. PMID- 22321111 TI - Early and late results of surgical treatment for ventricular septal rupture with and without use of the infarction exclusion technique--experience with two- and three-sheet modification. AB - BACKGROUND: Ventricular septal rupture (VSR) is an infrequent but life threatening situation. Although outcomes have improved with the introduction of infarction exclusion, we have experienced difficulty in determining the optimal patch size and shape for obtaining good outcomes. Therefore, we modified the infarction exclusion technique. Herein, we review our experience on the basis of early closure of VSR with and without use of the infarction exclusion technique. METHODS: We retrospectively analyzed the hospital records of 33 patients who underwent surgical treatment for VSR. We employed Dagget's method from 1982 to 1995, and then introduced the infarction exclusion technique in 1995. We have developed two modifications: the two-sheet single-patch technique and the three sheet double-patch technique. RESULTS: Overall hospital mortality was 41.9% and that of the infarction exclusion group was significantly lower than the hospital mortality rate of the noninfarction exclusion group (21% and 63%, respectively, p = 0.0266). Late mortality of survivors was low in all groups during the observation period. The three-sheet double-patch group showed no residual shunt. This difference in outcomes between the single-patch and double-patch groups was statistically significant (p = 0.0174). CONCLUSIONS: The two-sheet method facilitates the restoration of ventricular geometry. A double-patch using the three-sheet method may be useful for reducing residual shunt. PMID- 22321112 TI - Aortic regurgitation caused by Behcet's disease: surgical experience during an 11 year period. AB - BACKGROUND AND AIM OF THE STUDY: Aortic regurgitation (AR) caused by Behcet's disease is a rare clinical condition and surgical experience is limited. Many patients undergoing simple aortic valve replacement (AVR) required a second or third operation as a result of prosthetic valve dehiscence. We analyze our experience with surgical management for AR in Behcet's disease during an 11-year period. METHODS: From April 1997 through December 2008, 10 male patients (mean age, 38.4 +/- 6.9 years) with AR caused by Behcet's disease underwent surgical treatment. The primary procedures were AVR in seven cases and aortic root replacement in three (two Bentall, one Cabrol). The duration of follow-up was 5.3 +/- 3.6 years. RESULTS: In the seven patients with simple AVR, valve dehiscence occurred in six after an interval of 2.9 +/- 1.7 months, necessitating 11 reoperations (four redo AVRs, one redo redo-AVR, four aortic root replacements, and two heart transplants) with one early death. In aortic root replacement patients, two Bentall patients survived and required no reintervention, and the Cabrol patient died from electromechanical uncoupling one year postoperatively. Of the seven survivors, the definite procedure was aortic root replacement in four cases, heart transplantation in two, and AVR in one. CONCLUSIONS: The rate of valve dehiscence was high after isolated AVR in patients with AR caused by Behcet's disease. At the first operation, aortic root replacement should be the procedure of choice, preferably with a homograft. Heart transplantation might be a feasible alternative to aortic root replacement in selected patients. PMID- 22321113 TI - Transventricular edge-to-edge repair of the mitral valve during surgical ventricular restoration: review of the literature. AB - BACKGROUND: Mitral valve surgery for functional ischemic mitral regurgitation (MR) in high-risk patients, including those requiring multiple concomitant cardiac operations, carries a significant risk of morbidity and mortality. In patients undergoing surgical ventricular restoration, transventricular edge-to edge repair provides an effective alternative to conventional mitral valve surgery. We report such a case. METHODS: A 67-year-old male with ischemic cardiomyopathy and severe left ventricular dysfunction presented to our institution with a 3-month history of dyspnea on exertion, angina, and leg edema. He was found to have triple-vessel coronary artery disease, a severely dilated left ventricle with an apical aneurysm, and moderate-to-severe MR (3+). In addition to coronary artery bypass graft surgery, an edge-to-edge mitral valve repair was undertaken via a longitudinal ventriculotomy performed for concomitant surgical ventricular restoration. RESULTS: Total cardiopulmonary bypass and aortic cross-clamp times were 101 minutes and 86 minutes, respectively. Postoperative transesophageal echocardiography revealed no MR, and the patient was discharged home on postoperative day 9. A follow-up transthoracic echocardiogram revealed trace MR on postoperative day 15. At 11 months postoperative, the patient remains in New York Heart Association functional class I. CONCLUSION: Transventricular edge-to-edge repair of the mitral valve in patients with ischemic cardiomyopathy and functional MR undergoing SVR is a safe and effective alternative to conventional valve surgery, and should be considered in this high-risk population. PMID- 22321114 TI - Surgery for acute type A aortic dissection in octogenarians. AB - BACKGROUND AND AIM: Emergency surgery for type A aortic dissection (AAD) is associated with high mortality rates. The published outcomes of such surgery in aging patients are controversial and the optimal management for elderly patients has not been established. Our study aimed to evaluate the outcomes of surgery for AAD in patients over the age of 80 years. MATERIALS AND METHODS: Between January 1996 and January 2010, 236 patients underwent surgery for AAD, of which 15 patients were older than 80 years. We evaluated the operative mortality in the whole cohort compared to the outcomes in the elderly subgroup. We assessed the preoperative risks factors and quality of life after surgery by performance status and the patients' ability to return home. RESULTS: Operative mortality was higher in patients aged >80 years (40% vs. 18%, p = 0.04). The survival rate for patients >80 years at one, three, and five years was 53.3% +/- 0.12%, 42.6% +/- 0.14%, and 42.6% +/- 0.12%, respectively. Of the survivors, six patients were able to return home (40%) and the postoperative performance status was "3" in one patient, "2" in six patients, and "1" in two patients. A preoperative level of 2 or greater was found to be a significant risk factor (p = 0.04). CONCLUSION: Survival in octogenarians undergoing surgery for AAD is possible, and some patients were able to return home with a reasonable level of autonomy. Larger series will be needed to define the optimal management for octogenarians presenting with AAD. PMID- 22321115 TI - Use of the Batista procedure to discontinue bypass following aortic reimplantation of an anomalous left coronary artery. AB - A four-month-old infant with anomalous origin of the left coronary artery from the pulmonary artery developed severe left ventricular failure after aortic reimplantation, despite prolonged supportive cardiopulmonary bypass with high level inotropic support and several abortive attempts for discontinuation. The Batista procedure was performed and the patient was successfully weaned from bypass. Postoperative recovery was uneventful, and at one-year follow-up she remains asymptomatic. PMID- 22321116 TI - Surgical management of persistent left superior vena cava associated with an absent right superior vena cava. AB - A case of persistent left with absent right superior vena cava accompanied with atrial septal defect in a six-year-old girl is presented. This rare venous malformation was diagnosed incidentally during surgery when the pericardium was incised. An L-shape cannula was directly inserted into the left superior vena cava for cardiopulmonary bypass. The atrial septal defect was closed with a fresh autologous pericardial patch. The surgical management of this rare anomaly is the subject of this review. PMID- 22321108 TI - Regulation of mast cell responses in health and disease. AB - Mast cells are multifunctional cells that initiate not only IgE-dependent allergic diseases but also play a fundamental role in innate and adaptive immune responses to microbial infection. They are also thought to play a role in angiogenesis, tissue remodeling, wound healing, and tumor repression or growth. The broad scope of these physiologic and pathologic roles illustrates the flexible nature of mast cells, which is enabled in part by their phenotypic adaptability to different tissue microenvironments and their ability to generate and release a diverse array of bioactive mediators in response to multiple types of cell-surface and cytosolic receptors. There is increasing evidence from studies in cell cultures that release of these mediators can be selectively modulated depending on the types or groups of receptors activated. The intent of this review is to foster interest in the interplay among mast cell receptors to help understand the underlying mechanisms for each of the immunological and non immunological functions attributed to mast cells. The second intent of this review is to assess the pathophysiologic roles of mast cells and their products in health and disease. Although mast cells have a sufficient repertoire of bioactive mediators to mount effective innate and adaptive defense mechanisms against invading microorganisms, these same mediators can adversely affect surrounding tissues in the host, resulting in autoimmune disease as well as allergic disorders. PMID- 22321117 TI - Temporary mechanical circulatory support for Takotsubo cardiomyopathy secondary to primary mediastinal B-cell lymphoma. AB - BACKGROUND: Left heart mechanical circulatory support (MCS) through the left chest via the pulmonary vein and descending thoracic aorta is a good option for patients with an inaccessible anterior mediastinum and/or poor peripheral access. MATERIALS AND METHODS: We report the case of a 19-year-old small female with a newly discovered bulky primary mediastinal diffuse large B-cell lymphoma (PMBL) who developed refractory inverted Takotsubo cardiomyopathy (TC) with cardiogenic shock. RESULTS: Temporary MCS was implemented in order to stabilize the patient and proceed with a chemotherapy treatment. Given the patient's oncologic "frozen" mediastinum and the presence of poor peripheral arterial access, the left heart temporary MCS was successfully implanted through a left mini-thoracotomy via the left inferior pulmonary vein and descending thoracic aorta. CONCLUSIONS: This is the first report of temporary MCS to treat inverted TC and diffuse PMBL. PMID- 22321118 TI - The Cohn felt plug: an effective HeartMate II(r) reimplantation technique. AB - We report the first documented case of HeartMate II(r) left ventricular assist device (LVAD) reimplantation following Cohn Teflon felt plug repair of the initial left ventricular apical cannulation site. This case highlights the current limitations of the predictability of myocardial recovery while describing an effective technique for possible future LVAD reimplantation. PMID- 22321119 TI - Aortic dissections following heart transplantations. AB - BACKGROUND: Aortic dissection in a cardiac allograft is an uncommon complication of heart transplantation with only few cases reported in the literature. METHOD: We report a case of 46-year-old female who underwent orthotopic heart transplantation for dilated cardiomyopathy 22 years earlier. During surveillance echocardiographic examination she was diagnosed with type A aortic dissection limited to the donor aorta. The aortic root was successfully replaced using a valve-sparing David procedure. The pathogenesis and surgical management of these dissections is reviewed. CONCLUSION: Appropriate surgical repair performed in a timely fashion leads to excellent results improving the prognosis of these patients. PMID- 22321120 TI - Relationship between left atrial volume and atrial fibrillation following coronary artery bypass grafting. AB - BACKGROUND: Atrial fibrillation (AF) is a common complication of coronary artery bypass grafting (CABG). However, limited information is available about the role of preoperative echocardiographic left atrial evaluation to predict AF occurrence after CABG. Thus, we prospectively compared the ability of echocardiographic measurements of left atrial volume to predict AF in this setting. METHODS: From January to December 2009, 220 patients (75% males, 66.8 +/- 10.0 years) met the inclusion criteria of our study (isolated and elective CABG, no valve surgery, no permanent AF, or other chronic atrial arrhythmias). The day before CABG a complete echocardiographic evaluation was performed with left atrial volume measurements. The primary endpoint of the study was postoperative AF (POAF) lasting >30 seconds. RESULTS: POAF was observed in 61 patients (27.7%). POAF patients showed increased left atrial M-mode anteroposterior dimension (41.2 +/- 6.4 mm vs. 43.6 +/- 7.3 mm; p = 0.020) and increased left atrial volume (59.0 +/- 18.3 mL vs. 70.6 +/- 28.1 mL; p = 0.0004). Left atrial volume was an independent risk factor for POAF (OR 10.03; 95% CI 10.01 to 10.05; p = 0.01), along with postoperative bleeding with hemoglobin levels below 8 g/dL (OR 20.84; 95% CI 10.12 to 70.19; p = 0.03) and preoperative left ventricular ejection fraction below 40% (OR 10.08; 95% CI 10.01 to 10.15; p = 0.02). Conversely, preoperative statin therapy exerted a protective role (OR 0.30; 95% CI 0.12 to 0.74; p = 0.009). CONCLUSION: Preoperative echocardiographic evaluation of patients with isolated CABG demonstrated that left atrium volume measurements were independently correlated to the occurrence of POAF. Further investigations should focus on the opportunity to target prophylactic antiarrhythmic treatments to patients with large left atrial volumes. PMID- 22321121 TI - The increasing prevalence of serologic markers for syphilis among Chinese blood donors in 2008 through 2010 during a syphilis epidemic. AB - BACKGROUND: In China, the growing syphilis epidemic parallels the spread of human immunodeficiency virus (HIV) in the general population. This study evaluated the prevalence and incidence of serologic markers for syphilis among donors at five Chinese blood centers. STUDY DESIGN AND METHODS: We examined whole blood and apheresis donations collected from January 2008 through December 2010. Postdonation testing of syphilis was conducted using two different Treponema pallidum antibody enzyme-linked immunosorbent assay kits. The prevalence of serologic markers for syphilis (%), and the rate of coinfection with HIV-1/2, hepatitis B virus (HBV), and hepatitis C virus (HCV) were calculated. A multivariable logistic regression analysis was conducted examining donor characteristics associated with positive syphilis serology. Seroconversion rate and syphilis incidence were estimated. RESULTS: Of 801,511 donations, 60% were from first-time donors and 40% were from repeat donors. There was a significant increase in syphilis serologic markers among first-time donors with 0.41, 0.45, and 0.57% positivity over 3 years (p < 0.001). Approximately 2.8, 0.8, and 0.5% of HIV-1/2-, HBV-, and HCV-positive donations also tested reactive for syphilis. Logistic regression results suggest that first-time donors were nine times more likely to be syphilis positive than repeat donors. Higher syphilis positivity was associated with donors older than 25 years and with less education. Estimated incidence among repeat donations was 33 (95% confidence interval, 29-39) per 100,000 person-years. CONCLUSION: The increase in syphilis serologic prevalence reflected the syphilis epidemic in the general population. Without screening, most of these syphilis-positive donations would get into the blood supply. Thus, during a syphilis epidemic, continued syphilis screening of blood donations may be important to maintain blood safety and public health. PMID- 22321122 TI - Development of a technique for efficient gene transfer to antral follicular cells in the mouse ovary. AB - Ovarian follicle development is a complex process mediated by interactions between oocytes and surrounding follicular cells. In an ovary, oocytes are ultimately released from Graafian follicles, which develop from antral follicles localized near the surface of an ovary. To examine the molecular interaction between these 2 cell types, direct gene transfer to follicular cells as well as oocytes appears to be a promising approach, but few studies have applied this technique. The aim of the present study was to develop a technique for gene transfer to antral follicle cells based on their accessibility near the surface of an ovary. B6C3F1 (a hybrid between C57BL6/N and C3H/HeN) female mice aged 4 or 8 w were anesthesized and their ovaries were exposed. About 100 nl of a solution containing reporter plasmid DNA (0.5 ug/MUl) and 0.1% trypan blue was injected into a follicle using a glass micropipette attached to the mouthpiece. A total of 6 follicles were injected per ovary. After injection, the ovary was immediately subjected to in vivo electroporation (EP) using an electroporator with 8 square electric pulses of 50 ms and 50 V. After 24 h, the treated ovaries were excised to examine the expression of reporter constructs by histochemistry. All the injected follicles expressed reporter genes to different extents. Inspection of cryostat sections of ovaries injected with the lacZ expression plasmid demonstrated that 50-100% of follicular cells within a follicle were successfully transfected. However, there were no oocytes within the antral follicles that were negative for such staining (15 follicles tested). Similar results were obtained when the enhanced green fluorescent protein expression plasmid was introduced. The present method based on in vivo EP was found to be very effective for transfection of follicular cells. This approach might be useful to explore the roles of genes related to oogenesis/folliculogenesis, and for reproductive manipulation targeted to antral follicles. PMID- 22321123 TI - Making sanitation count: developing and testing a device for assessing latrine use in low-income settings. AB - While efforts are underway to expand latrine coverage to an estimated 2.6 billion people who lack access to improved sanitation, there is evidence that actual use of latrines is suboptimal, limiting the potential health and environmental gains from containment of human excreta. We developed a passive latrine use monitor (PLUM) and compared its ability to measure latrine activity with structured observation. Each PLUM consisted of a passive infrared motion detector, microcontroller, data storage card, and batteries mounted in a small plastic housing that was positioned inside the latrine. During a field trial in Orissa, India, with ~115 households, the number of latrine events measured by the PLUMs was in good agreement with that measured by trained observers during 5 h of structured observation per device per week. A significant finding was that the presence of a human observer was associated with a statistically significant increase in the number of latrine events, i.e., the users modified their behavior in response to the observer. Another advantage of the PLUM was the ability to measure activity continuously for an entire week. A shortcoming of the PLUM was the inability to separate latrine events that occurred in immediate succession, leading to possible undercounting during high-traffic periods. The PLUM is a promising technology that can provide detailed measures of latrine use to improve the understanding of sanitation behaviors and how to modify them and for assessing the intended health, livelihood, and environmental benefits of improved sanitation. PMID- 22321124 TI - Insights from "Creating the Healthcare Workforce for the 21st Century" Conference. PMID- 22321125 TI - Care Continuum Alliance research update 2012. PMID- 22321126 TI - Response-guided therapy for patients with chronic hepatitis who have high viral loads of hepatitis C virus genotype 2. AB - AIM: We evaluated the efficacy of response-guided therapy in patients with hepatitis C virus (HCV) genotype 2. METHODS: We studied 105 patients with an HCV genotype 2 load of higher than 5.0 Log IU/mL who received more than 75% of the target dose of pegylated interferon plus ribavirin. Among patients with rapid viral response (RVR; no HCV RNA detected at week 4), 14 selected 16 weeks of therapy (group A), and 28 selected 24 weeks of therapy (group B). Among non-RVR patients, 40 selected 24 weeks of therapy (group C), and 19 selected 48 weeks of therapy (group D). RESULTS: All patients in group A and B achieved a sustained viral response (SVR). Clinical characteristics did not differ significantly between groups C and D. However, the proportion of patients in whom HCV RNA disappeared at a later week after starting treatment was higher in group D (P = 0.0578). SVR rate was 73% in C, and 79% in D. Among patients in whom HCV RNA disappeared between weeks 5 and 8, SVR was achieved in 28 (82%) of 34 patients in C and 10 (91%) of 11 patients in D. Among patients whose HCV RNA disappeared between weeks 9 and 12, SVR was achieved in one (20%) of five patients in C and five (63%) of eight patients in D (not statistically significant). CONCLUSIONS: 16 weeks of combination therapy could achieve an adequate antiviral effect for RVR patients. Extending therapy could not significantly improve SVR rate in non RVR patients. PMID- 22321127 TI - Myosin VI regulates actin dynamics and melanosome biogenesis. AB - Myosin VI has been implicated in various steps of organelle dynamics. However, the molecular mechanism by which this myosin contributes to membrane traffic is poorly understood. Here, we report that myosin VI is associated with a lysosome related organelle, the melanosome. Using an actin-based motility assay and video microscopy, we observed that myosin VI does not contribute to melanosome movements. Myosin VI expression regulates instead the organization of actin networks in the cytoplasm. Using a cell-free assay, we showed that myosin VI recruited actin at the surface of isolated melanosomes. Myosin VI is involved in the endocytic-recycling pathway, and this pathway contributes to the transport of a melanogenic enzyme to maturing melanosomes. We showed that depletion of myosin VI accumulated a melanogenic enzyme in enlarged melanosomes and increased their melanin content. We confirmed the requirement of myosin VI to regulate melanosome biogenesis by analysing the morphology of melanosomes in choroid cells from of the Snell's waltzer mice that do not express myosin VI. Together, our results provide new evidence that myosin VI regulates the organization of actin dynamics at the surface of a specialized organelle and unravel a novel function of this myosin in regulating the biogenesis of this organelle. PMID- 22321128 TI - A joint mixed effects dispersion model for menstrual cycle length and time-to pregnancy. AB - Menstrual cycle patterns are often used as indicators of female fecundity and are associated with hormonally dependent diseases such as breast cancer. A question of considerable interest is in identifying menstrual cycle patterns, and their association with fecundity. A source of data for addressing this question is prospective pregnancy studies that collect detailed information on reproductive aged women. However, methodological challenges exist in ascertaining the association between these two processes as the number of longitudinally measured menstrual cycles is relatively small and informatively censored by time to pregnancy (TTP), as well as the cycle length distribution being highly skewed. We propose a joint modeling approach with a mixed effects dispersion model for the menstrual cycle lengths and a discrete survival model for TTP to address this question. This allows us to assess the effect of important characteristics of menstrual cycle that are associated with fecundity. We are also able to assess the effect of fecundity predictors such as age at menarche, age, and parity on both these processes. An advantage of the proposed approach is the prediction of the TTP, thus allowing us to study the efficacy of menstrual cycle characteristics in predicting fecundity. We analyze two prospective pregnancy studies to illustrate our proposed method by building a model based on the Oxford Conception Study, and predicting for the New York State Angler Cohort Prospective Pregnancy Study. Our analysis has relevant findings for assessing fecundity. PMID- 22321129 TI - Heavy metal stress can prime for herbivore-induced plant volatile emission. AB - Heavy metals are important pollutants that can severely impact ecological foodwebs. In addition to direct toxic effects, these contaminants have been suggested to disrupt chemical communication channels between plants and insects that rely on volatile organic compounds (VOCs). We investigated how different concentrations of copper (Cu) and cadmium (Cd) stress affect the capacity of Zea mays to synthesize VOCs in the presence and absence of herbivorous insects. Hydroponically grown maize exposed to a high and low concentration of either Cu or Cd showed stunted growth and lower photosynthetic capacities. Herbivores feeding on stressed plants also had attenuated growth rates. Heavy metal treatment alone did not induce VOC emission in maize plants; however, the higher Cu dose was found to prime for enhanced volatile production that can be triggered by caterpillar feeding. Cu stress correlated with increased levels of reactive oxygen species in roots and priming of herbivore-induced jasmonic acid in leaves. Plants challenged with Cd and herbivory did not differ in responses compared with herbivore-damaged controls with no heavy metals added to the substrate. For Cu stress, our results support the 'single biochemical mechanism for multiple stressors' model which predicts overlapping signalling and responses to abiotic and biotic stress factors. PMID- 22321130 TI - Thermally induced degradation of sulfur-containing aliphatic glucosinolates in broccoli sprouts (Brassica oleracea var. italica) and model systems. AB - Processing reduces the glucosinolate (GSL) content of plant food, among other aspects due to thermally induced degradation. Since there is little information about the thermal stability of GSL and formation of corresponding breakdown products, the thermally induced degradation of sulfur-containing aliphatic GSL was studied in broccoli sprouts and with isolated GSL in dry medium at different temperatures as well as in aqueous medium at different pH values. Desulfo-GSL have been analyzed with HPLC-DAD, while breakdown products were estimated using GC-FID. Whereas in the broccoli sprouts structural differences of the GSL with regard to thermal stability exist, the various isolated sulfur-containing aliphatic GSL degraded nearly equally and were in general more stable. In broccoli sprouts, methylsulfanylalkyl GSL were more susceptible to degradation at high temperatures, whereas methylsulfinylalkyl GSL were revealed to be more affected in aqueous medium under alkaline conditions. Besides small amounts of isothiocyanates, the main thermally induced breakdown products of sulfur containing aliphatic GSL were nitriles. Although they were most rapidly formed at comparatively high temperatures under dry heat conditions, their highest concentrations were found after cooking in acidic medium, conditions being typical for domestic processing. PMID- 22321131 TI - Drug education in Victorian schools (DEVS): the study protocol for a harm reduction focused school drug education trial. AB - BACKGROUND: This study seeks to extend earlier Australian school drug education research by developing and measuring the effectiveness of a comprehensive, evidence-based, harm reduction focused school drug education program for junior secondary students aged 13 to 15 years. The intervention draws on the recent literature as to the common elements in effective school curriculum. It seeks to incorporate the social influence of parents through home activities. It also emphasises the use of appropriate pedagogy in the delivery of classroom lessons. METHODS/DESIGN: A cluster randomised school drug education trial will be conducted with 1746 junior high school students in 21 Victorian secondary schools over a period of three years. Both the schools and students have actively consented to participate in the study. The education program comprises ten lessons in year eight (13-14 year olds) and eight in year nine (14-15 year olds) that address issues around the use of alcohol, tobacco, cannabis and other illicit drugs. Control students will receive the drug education normally provided in their schools. Students will be tested at baseline, at the end of each intervention year and also at the end of year ten. A self completion questionnaire will be used to collect information on knowledge, patterns and context of use, attitudes and harms experienced in relation to alcohol, tobacco, cannabis and other illicit drug use. Multi-level modelling will be the method of analysis because it can best accommodate hierarchically structured data. All analyses will be conducted on an Intent-to-Treat basis. In addition, focus groups will be conducted with teachers and students in five of the 14 intervention schools, subsequent to delivery of the year eight and nine programs. This will provide qualitative data about the effectiveness of the lessons and the relevance of the materials. DISCUSSION: The benefits of this drug education study derive both from the knowledge gained by trialling an optimum combination of innovative, harm reduction approaches with a large, student sample, and the resultant product. The research will provide better understanding of what benefits can be achieved by harm reduction education. It will also produce an intervention, dealing with both licit and illicit drug use that has been thoroughly evaluated in terms of its efficacy, and informed by teacher and student feedback. This makes available to schools a comprehensive drug education package with prevention characteristics and useability that are well understood. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000079842. PMID- 22321132 TI - The economic benefits of negative pressure wound therapy in community-based wound care in the NHS. AB - The human and economic costs of wounds are of major concern within today's National Health Service. Advances in wound care technology have been shown to be beneficial both in healing and in relation to patient quality of life. Negative pressure has often been associated with high-cost care and restricted to use in the secondary care setting. There is growing use of negative pressure within the community, and this has the potential to benefit the patient and the service by providing quality care in the patient's home setting. Three community sites were chosen to monitor their use of negative pressure wound therapy (NPWT) over a period of 2 years, and this paper presents some of the key findings of this work. The data generated has been used to help target resources and prevent misuse of therapy. Cost per patient episode has been calculated, and this can be compared to similar costs in secondary care, showing significant savings if patients are discharged earlier from secondary care. There is also an increased demand for more patients with complex wounds to be cared for in the community, and in the future, it is likely that community initiated NPWT may become more common. Early analysis of the data showed that the average cost of dressing complex wounds would be significantly less than using traditional dressings, where increased nursing visits could increase costs. There is a compelling argument for more negative pressure to be used and initiated in the community, based not only on improved quality of life for patients but also on the economic benefits of the therapy. PMID- 22321133 TI - Language performance and auditory evoked fields in 2- to 5-year-old children. AB - Language development progresses at a dramatic rate in preschool children. As rapid temporal processing of speech signals is important in daily colloquial environments, we performed magnetoencephalography (MEG) to investigate the linkage between speech-evoked responses during rapid-rate stimulus presentation (interstimulus interval < 1 s) and language performance in 2- to 5-year-old children (n = 59). Our results indicated that syllables with this short stimulus interval evoked detectable P50m, but not N100m, in most participants, indicating a marked influence of longer neuronal refractory period for stimulation. The results of equivalent dipole estimation showed that the intensity of the P50m component in the left hemisphere was positively correlated with language performance (conceptual inference ability). The observed positive correlations were suggested to reflect the maturation of synaptic organisation or axonal maturation and myelination underlying the acquisition of linguistic abilities. The present study is among the first to use MEG to study brain maturation pertaining to language abilities in preschool children. PMID- 22321134 TI - Surveillance status and recent data for Mycoplasma pneumoniae infections in the European Union and European Economic Area, January 2012. AB - In January 2012, the European Centre for Disease Prevention and Control (ECDC) conducted an email based survey of European Union and European Economic Area countries to describe the existing surveillance activities for Mycoplasma pneumoniae infections, recent findings and existence of clinical guidelines for the treatment of M. pneumoniae infection. Of the 20 countries that participated in the survey, seven reported increases in M. pneumoniae infections observed during the autumn and winter of 2011. PMID- 22321135 TI - Increased incidence of Mycoplasma pneumoniae infection in Finland, 2010-2011. AB - The number of cases of Mycoplasma pneumoniae infection detected by laboratory based surveillance increased in Finland in late 2010. During 2011, the number of cases was four times higher than during the previous epidemic in 2005. The 2011 epidemic affected mostly school-age children. The increased number of cases was probably not due to changes in laboratory procedures, but public interest may have had an effect, since the number of Google queries followed closely the epidemic curve. PMID- 22321136 TI - Increased incidence of Mycoplasma pneumoniae infection in Norway 2011. AB - Epidemics of Mycoplasma pneumoniae have recently been reported from England and Wales and from Denmark. A similar increase in M. pneumoniae infections was noted in Norway late autumn 2011.The epidemic has resulted in shortage of erythromycin and the use of alternative antibiotics has been recommended. PMID- 22321137 TI - Epidemic of Mycoplasma pneumoniae infection in Denmark, 2010 and 2011. AB - Denmark experienced two waves of Mycoplasma pneumoniae infection during autumn and early winter in 2010 and 2011, respectively. Both affected the whole country. The proportion of positive results was almost the same for both, indicating that the two waves were probably of equal size. High macrolide consumption during the epidemics did not seem to affect levels of macrolide resistance in M. pneumoniae, which remain low in Demark (1% to 3%). PMID- 22321138 TI - Nationwide outbreak of Salmonella enterica serotype 4,[5],12:i:- infection associated with consumption of dried pork sausage, France, November to December 2011. AB - An outbreak of the monophasic variant of Salmonella enterica serotype 4,[5],12:i: occurred in November and December 2011 in France. Epidemiological investigation and food investigation with the help of supermarket loyalty cards suggested dried pork sausage from one producer as the most likely source of the outbreak. Despite the absence of positive food samples, control measures including withdrawal and recall were implemented. PMID- 22321139 TI - Outbreak of cryptosporidiosis in a child day-care centre in Gipuzkoa, Spain, October to December 2011. AB - From October to December 2011, an outbreak of 26 cases of cryptosporidiosis occurred in a day-care centre in Gipuzkoa, Spain. The infection spread from person to person and affected 24 children under two years of age (attack rate: 38%) and two caregivers. Cryptosporidium oocysts were observed in 10 of 15 samples. During 2010, only four cases of cryptosporidium were detected in Gipuzkoa, and 27 overall in Spain. PMID- 22321140 TI - An evidence-based review of peritonsillar abscess. AB - OBJECTIVE OF REVIEW: We present the current literature surrounding peritonsillar abscess management highlighting areas of controversy. TYPE OF REVIEW AND SEARCH STRATEGY: Literature review using Medline and Embase databases (search terms 'peritonsillar abscess', 'peritonsillar infection' and 'quinsy') limited to articles published from 1991 to 2011 (English language). RESULTS: (i) INVESTIGATIONS: Intraoral ultrasound has a sensitivity and specificity of between 89-95% and 79-100%, respectively, for correctly diagnosing peritonsillar abscess and is underutilised currently. (ii) Medical management: Steroids can effectively aid recovery, reducing hospitalisation time and improving symptom relief; however, further study is needed, especially related to risk and cost benefit. Penicillin and metronidazole are an effective combination in 98-99% of cases of peritonsillar abscess. (iii) Surgical management: Overall, there is no convincing evidence in favour of either aspiration or incision & drainage. Quinsy tonsillectomy is subject to great geographical variation, however, is a safe procedure and reduces overall recovery time when compared with interval tonsillectomy. (iv) Admission: peritonsillar abscess can be effectively managed as an outpatient in many cases. (v) Further management: Overall, the recurrence rate of peritonsillar abscess is poorly defined but estimated as 9-22% based on current evidence. Interval tonsillectomy may be indicated in selected groups of patients at high risk of recurrence. CONCLUSIONS: Peritonsillar abscess is a common condition with increasing incidence. We demonstrate the potential for evidence-based modifications in clinical management. However, lack of national consensus may mean that this evidence base is not being adequately exploited in current practice. A national audit of peritonsillar abscess management, in particular looking at recurrence rates and patient experience with different management strategies, appears indicated. PMID- 22321141 TI - Sternotomy following minimally invasive thoracoscopic procedures: a word of caution. AB - An increasing number of patients with previous minimally invasive thoracic procedures for anterior mediastinal tumors are now requiring cardiac surgery. This paper highlights the potential damage that can occur when standard sternal splitting techniques are used in these patients. PMID- 22321142 TI - Trypanosoma cruzi infection in North America and Spain: evidence in support of transfusion transmission. AB - BACKGROUND: The United States, Canada, and Spain perform selective testing of blood donors for Trypanosoma cruzi infection (Chagas disease) to prevent transfusion transmission. The donor, product, and patient characteristics associated with transfusion-transmitted infections are reviewed and the infectivity of components from donors with serologic evidence of infection is estimated. STUDY DESIGN AND METHODS: A systematic review of transfusion transmitted T. cruzi cases and recipient tracing undertaken in North America and Spain is described. Cases were assessed for the imputability of the evidence for transfusion transmission. RESULTS: T. cruzi infection in 20 transfusion recipients was linked to 18 serologically confirmed donors between 1987 and 2011, including 11 identified only by recipient tracing. Cases were geographically widely distributed and were not associated with incident or autochthonous infections. Index clinical cases were described only in immunocompromised patients. All definite transmissions (n = 11) implicated apheresis or whole blood derived platelets (PLTs), including leukoreduced and irradiated products. There is no evidence of transmission by red blood cells (RBCs) or frozen products, while transmission by whole blood transfusion remains a possibility. Recipient tracing reveals low component infectivity from serologically confirmed, infected donors of 1.7% (95% confidence interval [CI], 0.7%-3.5%) overall: 13.3% (95% CI, 5.6%-25.7%) for PLTs, 0.0% (95% CI, 0.0%-1.5%) for RBCs, and 0.0% (95% CI, 0% 3.7%) for plasma and cryoprecipitate. CONCLUSIONS: T. cruzi is transmitted by PLT components from some donors with serologic evidence of infection. Evidence of transmission before the implementation of widespread testing in the countries studied is sparse, and selective testing of only PLT and fresh whole blood donations should be considered. PMID- 22321143 TI - Perianal necrotizing fasciitis treated with a loose-seton technique. AB - AIM: The study evaluated the effect of a loose-seton technique for perianal necrotizing fasciitis. METHOD: The medical records of seven patients with perianal necrotizing fasciitis treated by the loose-seton technique between December 2005 and June 2010 were reviewed. Age, gender, status of diabetes mellitus, duration of symptoms, the length of hospital stay and number of debridements were investigated. RESULTS: Five of the patients were men. The mean age was 53 years and the range was 43-79 years. All seven patients had a past history of acute perianal abscess. Six (85.7%) patients had diabetes mellitus. The mean time for removal of the seton was 24 (14-32) days and the mean hospitalization time was 31 (23-45) days. All patients had primary wound healing. There was no mortality. At a median follow-up 18 (6-60) months one patient required inpatient treatment with cutting-seton for complex anal fistula after 11 months. All patients had normal faecal continence and none of them required a reconstructive procedure during the follow-up. CONCLUSION: The loose-seton technique is an effective treatment for perianal necrotizing fasciitis. The advantages include inhibiting the spread of inflammation, reducing the frequency of debridements, decreasing the area of the wound and limiting extensive scar formation. PMID- 22321144 TI - Investigation of the disparity between New York City and national prevalence of nonspecific psychological distress among Hispanics. AB - INTRODUCTION: In New York City, the age-adjusted prevalence of nonspecific psychological distress (NPD) among Hispanics is twice that of non-Hispanic whites; nationally, there is little Hispanic-white disparity. We aimed to explain the pattern of disparity in New York City. METHODS: Data came from the 2006 National Health Interview Survey and 2006 Community Health Survey in New York City. Respondents with scores higher than 12 on the K6, a brief scale used to screen for mental health disorders, were defined as having NPD. Multivariate analyses controlled for Hispanic ancestry, socioeconomic status (education, employment, and income), nativity, language of interview, and health characteristics. RESULTS: In New York City, the disparity between Hispanics and whites was fully explained after accounting for the disproportionate concentration of low socioeconomic status among Hispanics (odds ratio for NPD, 0.81; 95% confidence interval, 0.60-1.11). These factors also partially accounted for differences between Hispanics in New York City and the United States, but the prevalence of NPD overall in New York City remained elevated relative to the United States. CONCLUSION: Elevated NPD prevalence among New York City Hispanics was primarily attributable to large disparities in socioeconomic status; differences between New York City and the United States remained but were not specific to Hispanics. Interventions in New York City aimed at addressing racial/ethnic disparities in health may overlap with those addressing socioeconomic inequalities. Further study into the higher overall prevalence of NPD in New York City will be necessary to inform the design and targeting of interventions. PMID- 22321145 TI - Associations between sociodemographic characteristics and perceptions of the built environment with the frequency, type, and duration of physical activity among trail users. AB - INTRODUCTION: Rail trails are elements of the built environment that support the Task Force on Community Preventive Services' recommendation to create, or enhance access to, places for physical activity (PA). The purpose of this study was to examine the associations between sociodemographic characteristics and perceptions of the built environment with the frequency, type, and duration of PA among users of an urban, paved rail trail segment. METHODS: Interviewers conducted intercept surveys with 431 rail trail users and analyzed data by using logistic regression to estimate odds ratios between sociodemographic characteristics and perceptions of the built environment on the frequency, type, and duration of PA performed on the trail. RESULTS: Adults who used the trail in the cool months, traveled to the trail by a motorized vehicle, used the trail with others, and had some graduate school education visited the trail less often. Younger adults, men, whites, and those with some graduate school education were more likely to engage in vigorous activities on the trail. Adults who traveled to the trail by a motorized vehicle spent more time engaged in PA on the trail. CONCLUSION: Our results suggest that the most frequent users of a rail trail for PA are those who use the trail alone and travel to the trail by bicycle or on foot. Trails are an aspect of the built environment that supports active lifestyles, and future studies should evaluate different types of trails among more diverse populations and locations. PMID- 22321146 TI - A population approach to mitigating the long-term health effects of combat deployments. AB - A major focus of the mission of the US Department of Veterans Affairs (VA) is to respond to the needs of military personnel returning from war. Given the broad spectrum of the potential effects of combat deployment on the health and well being of service members, VA is increasingly oriented toward comprehensive postcombat support, health promotion, disease prevention, and proactive approaches to caring for combat veterans. This article briefly summarizes the health care needs of service members returning from Afghanistan and Iraq, describes VA's approaches to addressing their needs, and outlines VA's evolving vision for how to apply principles of population health management to ensure prompt and effective response to the postdeployment needs of veterans returning from future conflicts. At the heart of postcombat care will be population-based approaches oriented to health recovery using interdisciplinary, team-based platforms. PMID- 22321147 TI - Chronic diseases in male veterans with multiple sclerosis. AB - INTRODUCTION: Chronic disease risk may be high in people with multiple sclerosis (MS). Our objective was to identify chronic health conditions that may disproportionately affect male veterans with MS. METHODS: We collected primary survey data for male veterans with MS (n = 1,142) in 2003 and 2004 and compared the data with 2003 Behavioral Risk Factor Surveillance System secondary data for comparison groups without MS (veteran population, n = 31,500; general population = 68,357). We compared disease prevalence by group and identified variables associated with chronic diseases in male veterans with MS. RESULTS: Overall, veterans with MS had a high prevalence of hypercholesterolemia (49%), hypertension (47%), diabetes (16%), coronary heart disease (11%), and stroke (7%). Overall and for the subset of people aged 50 years or older, diabetes, hypertension, hypercholesterolemia, coronary heart disease, and stroke were significantly more prevalent among male veterans with MS than among the general population. Diabetes, hypertension, hypercholesterolemia, and stroke were more prevalent overall among male veterans with MS than among the general veteran population; however, except for stroke, differences were not significant for the group aged 50 or older. Explanatory variables (eg, age, education, race) and dynamic associations between conditions (higher odds for each when >= 1 of the other conditions were present) for chronic disease in men with MS were similar to findings in the general population literature for select conditions. CONCLUSION: These findings raise awareness of chronic disease in a veteran cohort and help bridge a gap in the literature on chronic disease epidemiology in men with MS. We identified chronic disease priorities that may benefit from focused interventions to reduce disparities. PMID- 22321148 TI - Childhood consumption of fruit and vegetables across England: a study of 2306 6-7 year-olds in 2007. AB - The School Fruit and Vegetable Scheme (SFVS) provides children in government-run schools in England with a free piece of fruit or a vegetable each school day for the first 3 years of school. The present study examines the impact of the SFVS, in terms of its contribution towards the total daily intake of fruit and vegetables by children across England. Quantitative dietary data were collected from 2306 children in their third year of school, from 128 schools, using a 24 h food diary. The data were examined at different spatial scales, and variations in the impact of the scheme across areas with different socio-economic characteristics were analysed using a deprivation index and a geodemographic classification. The uptake of the SFVS and the total intake of fruit and vegetables by children varied across different parts of England. Participation in the SFVS was positively associated with fruit and vegetable consumption. That is, in any one area, those children who participated in the SFVS consumed more fruit and vegetables. However, children living in deprived areas still consumed less fruit and vegetables than children living in more advantaged areas: the mean daily frequency of fruit and vegetables consumed, and rates of consumption of fruit or vegetables five times or more per d, decreased as deprivation increased (r -0.860; P = 0.001; r -0.842; P = 0.002). So the SFVS does not eliminate the socio-economic gradient in fruit and vegetable consumption, but it does help to increase fruit and vegetable consumption in deprived (and affluent) areas. PMID- 22321149 TI - Elevated expression of angiomodulin (AGM/IGFBP-rP1) in tumor stroma and its roles in fibroblast activation. AB - Angiomodulin (AGM/IGFBP-rP1), a glycoprotein of about 30 kDa, is overexpressed in tumor vasculature as well as some human cancer cell lines, but it has been suggested to be a tumor suppressor. To elucidate roles of angiomodulin (AGM) in tumor progression, we here examined distribution of AGM in three types of human cancer tissues by immunohistochemistry. The results showed that AGM was overexpressed in the stroma as well as the vasculature surrounding tumor cells in the human cancer tissues. AGM and alpha-smooth muscle actin (alpha-SMA) as an activated fibroblast marker were often colocalized in cancer-associated fibroblasts (CAFs). In vitro analysis indicated that transforming growth factor (TGF)-beta1 might be an important inducer of AGM in normal human fibroblasts. AGM strongly stimulated the expression of fibronectin and weakly that of alpha-SMA in normal fibroblasts. AGM significantly stimulated the proliferation and migration of fibroblasts. The AGM-induced expression of fibronectin and alpha-SMA was blocked by a TGF-beta signal inhibitor but neither the stimulation of cell growth nor migration. These results imply that AGM activates normal fibroblasts by TGF beta-dependent and independent mechanisms. These findings also suggest that AGM and TGF-beta1 cooperatively or complementarily contribute to the stromal activation and connective tissue formation in human cancer tissues, contributing to tumor progression. PMID- 22321150 TI - Cyclosporine-A inhibits MMP-2 and -9 activities in the presence of Porphyromonas gingivalis lipopolysaccharide: an experiment in human gingival fibroblast and U937 macrophage co-culture. AB - BACKGROUND AND OBJECTIVE: Studies have shown that bacterial plaque and the associated gingival inflammation increase the severity of gingival overgrowth induced by cyclosporine-A (CsA). This in vitro study aimed to evaluate the effect of CsA on the activities of MMPs from the co-culture of human gingival fibroblasts and U937 macrophages in the presence or absence of Porphyromonas gingivalis lipopolysaccharide (LPS). MATERIAL AND METHODS: Activities of pro-MMP 2, MMP-2 and pro-MMP-9 in the supernatants of independent cultures and co cultures were examined by zymography. RT-PCR was selected to evaluate the expression of mRNA for membrane type-1 (MT1) MMP in the co-cultures. RESULTS: Activities of MMPs in the co-cultures were significantly greater when compared with any of the independent cultures. Lipopolysaccharide significantly increased the MMP activities in a dose-dependent manner in the co-cultures, whereas CsA inhibited these activities. In the presence of both CsA and LPS, the MMP activities inhibited by CsA could still be observed in the co-cultures. In the individual cultures, in contrast, the CsA-inhibited MMP activities, in the presence of LPS, were minimally detected. The mRNA expression of MT1-MMP was significantly enhanced after LPS treatment; however, this enhancement was inhibited by CsA. CONCLUSION: This study demonstrated that, in co-cultures of human gingival fibroblasts and U937 macrophages, CsA could inhibit MMP activities in the presence of P. gingivalis LPS. It might be part of the underlying reason for the persistent overgrowth of gingiva seen when bacterial plaque and local inflammation are present during CsA therapy. PMID- 22321151 TI - Glycogenotic hepatocellular carcinoma with glycogen-ground-glass hepatocytes: histological, histochemical and microbiochemical characterization of the novel variant. PMID- 22321152 TI - QTLs for resistance to the false brome rust Puccinia brachypodii in the model grass Brachypodium distachyon L. AB - The potential of the model grass Brachypodium distachyon L. (Brachypodium) for studying grass-pathogen interactions is still underexploited. We aimed to identify genomic regions in Brachypodium associated with quantitative resistance to the false brome rust fungus Puccinia brachypodii . The inbred lines Bd3-1 and Bd1-1, differing in their level of resistance to P. brachypodii, were crossed to develop an F(2) population. This was evaluated for reaction to a virulent isolate of P. brachypodii at both the seedling and advanced growth stages. To validate the results obtained on the F(2), resistance was quantified in F(2)-derived F(3) families in two experiments. Disease evaluations showed quantitative and transgressive segregation for resistance. A new AFLP-based Brachypodium linkage map consisting of 203 loci and spanning 812 cM was developed and anchored to the genome sequence with SSR and SNP markers. Three false brome rust resistance QTLs were identified on chromosomes 2, 3, and 4, and they were detected across experiments. This study is the first quantitative trait analysis in Brachypodium. Resistance to P. brachypodii was governed by a few QTLs: two acting at the seedling stage and one acting at both seedling and advanced growth stages. The results obtained offer perspectives to elucidate the molecular basis of quantitative resistance to rust fungi. PMID- 22321153 TI - Tin oxide nanosheet assembly for hydrophobic/hydrophilic coating and cancer sensing. AB - Tin oxide nanosheets were crystallized on transparent conductive oxide substrates of fluorine-doped tin oxide in aqueous solutions. The nanosheets had chemical ratio of Sn:O:F = 1:1.85:0.076, suggesting fluorine doping into SnO(2). They were hydrophobic surfaces with contact angle of 140 degrees . They were converted to hydrophilic surfaces with contact angle of below 1 degrees by light irradiation. The simple water process will be applied to surface coating of polymers, metals, biomaterials, papers, etc. Furthermore, the tin oxide nanosheets were modified with dye-labeled monoclonal antibody. Monoclonal antibody reacts with human alpha fetoprotein in blood serum of hepatocellular cancer patient. Photoluminescence and photocurrent were obtained from the nanosheets under excitation light. Photoelectric conversion was an essence in the sensing system. The tin oxide nanosheets with dye-labeled prostate specific antigen will be used for electrodes of prostate cancer sensors. PMID- 22321154 TI - Epidermal growth factor receptor R521K polymorphism shows favorable outcomes in KRAS wild-type colorectal cancer patients treated with cetuximab-based chemotherapy. AB - The R521K polymorphism of epidermal growth factor receptor has attenuated affinity in ligand binding and proto-oncogene induction, which may affect the efficacy of cetuximab. We analyzed the effect of this polymorphism on the outcome of 112 patients with KRAS wild-type metastatic colorectal carcinoma treated with first-line cetuximab plus FOLFOX-4. The associations of this polymorphism with vascular endothelial growth factor (VEGF) expression and clinicopathologic characteristics were also examined. The results showed that the frequencies of the G/G, G/A, and A/A genotypes were 32.1% (n = 36), 42.9% (n = 48), and 25.0% (n = 28), respectively. A marked decrease in VEGF expression levels (66.7% vs 28.9%, P < 0.01) was observed in patients with 521A allele variants (Arg/Lys or Lys/Lys), which were associated with a decreased tumor size (55.6% vs 31.6%, P = 0.02), good histological differentiation (63.9% vs 85.5%, P = 0.01), decreased lymphovascular invasion (69.4% vs 39.5%, P < 0.01), and a higher response rate to cetuximab plus FOLFOX treatment (55.6% vs 78.9%, P = 0.01). In addition, this polymorphism was associated with a longer progression-free period (P = 0.001) and overall survival (P = 0.001). By multivariate analysis, this polymorphism was also identified as an independent prognostic factor. These data suggest that the R521K polymorphism of epidermal growth factor receptor, by reducing its activation and a consequential downregulation of its target genes, including VEGF, could be a key determinant of an increased response to cetuximab-based chemotherapy and a longer survival for KRAS wild-type colorectal carcinoma patients. PMID- 22321155 TI - Effect of whole-body vibration exercise on balance in women with fibromyalgia syndrome: a randomized controlled trial. AB - OBJECTIVES: This study evaluated the effectiveness of a 6-week "usual care" exercise program supplemented with whole-body vibration (WBV) to improve balance and strength in women with fibromyalgia (FM). DESIGN: This was a randomized controlled study. SETTINGS: The setting was a physical therapy department in an academic setting. SUBJECTS: The subjects were 30 postmenopausal women with FM (age: 59+/-7.90 years). INTERVENTIONS: Subjects were randomized into one of two groups: an experimental group (EG: n=15), which combined exercise training (2 days a week) with 3 days of WBV, and a control group (CG: n=15), who performed the same exercise training program (2 days a week) but without WBV. OUTCOME MEASURES: Balance and muscle strength were measured at baseline and after the 6 week intervention. RESULTS: Significant differences were found (p<0.05) between the study groups for the Medio-Lateral Stability Index (MLSI), when patients were assessed with their eyes open and closed. The effect size of the improvement was large with eyes closed (R2=0.260) and moderate when the eyes were open (R2=0.047). However, no significant differences were found (p>0.05) between the study groups for other outcomes. CONCLUSIONS: Women with FM may increase their MLSI by engaging in a 6-week traditional exercise program with supplementary WBV. This may have implications for falls prevention in this patient group. PMID- 22321156 TI - Human follicular dendritic cells promote the APC capability of B cells by enhancing CD86 expression levels. AB - Follicular dendritic cells (FDCs) are an essential cellular component of the germinal center (GC) and are believed to exert regulatory effects on the various stages of GC reactions. According to our previous reports, human FDCs express prostacyclin synthase, and prostacyclin analogues augment adhesion and co stimulatory molecules on the surface of activated B cells. These findings prompted us to investigate whether FDCs would contribute to the antigen presenting capability of B cells by using the well-established FDC-like cells, HK cells, and tonsillar B cells. Our results show that HK cells significantly enhance the expression levels of CD54, CD80, and CD86 on the surface of activated B cells. The enhancing effect of HK cells on CD86 is impeded by indomethacin and an EP4 antagonist, implying that a certain prostaglandin is mediating the up regulation. Prostacyclin indeed recapitulates the enhancing effect on CD86, which is inhibited by EP4 as well as IP antagonists. B cells co-cultured with HK cells exhibit an augmented APC activity, which is inhibited by CD86 neutralization. These results reveal another unrecognized function of human FDC. PMID- 22321157 TI - Assortative mating for relatedness in a large naturally occurring population of Drosophila melanogaster. AB - New theoretical work on kin selection and inclusive fitness benefits predicts that individuals will sometimes choose close or intermediate relatives as mates to maximize their fitness. However, empirical examples supporting such predictions are rare. In this study, we look for such evidence in a natural population of Drosophila melanogaster. We compared mating and nonmating individuals to test whether mating was nonrandom with respect to relatedness. Consistent with optimal inbreeding, males were more closely related to their mate than to randomly sampled females. However, all individuals collected mating showed higher relatedness and males were not significantly more related to their mate than to other mating females. We also found a negative relationship between relatedness and fecundity. Our results are consistent with the hypothesis that inclusive fitness benefits may drive inbreeding tolerance despite direct costs to fitness; however, an experimental approach is needed to investigate the link between mate preference and relatedness. PMID- 22321159 TI - Maladaptive variants of conscientiousness and agreeableness. AB - Although reasonably strong support has been obtained for the Five-Factor Model's (FFM) ability to account for the existing personality disorder (PD) constructs, the support for obsessive-compulsive PD (OCPD) and dependent PD (DPD) has been relatively less consistent. Specifically, the expected correlation between OCPD and the FFM trait of Conscientiousness has varied in magnitude across studies while DPD has, at times, also evinced rather weak relationships with FFM Agreeableness. We determined that these inconsistencies were due primarily to the reliance on FFM measures that lack adequate fidelity to assess the maladaptive aspects of high Conscientiousness and Agreeableness. When alternative measures were utilized, the correlations were generally large and in line with expectations. We conclude that OCPD and DPD can be fruitfully conceptualized within the FFM but encourage the use of measures that provide a comprehensive assessment of both the adaptive and maladaptive aspects of the FFM traits. PMID- 22321160 TI - Reliability of standardized patients used in a communication study on international nurses in the United States of America. AB - As an evaluation method, standardized patients have a long history in medical education and research yet are less established in nursing. This paper explores the reliability of using standardized patients as the evaluative method in a communication competence pilot study with international nurses. Standardized patients and second raters scored the same encounters. We examined the scores by intraclass correlation coefficients. Anecdotal comments by the two types of raters were assessed qualitatively to highlight similarities and areas of difference between them. The results of reliability analysis for standardized patients scores for the composite variables of Establishing Communicative Rapport, Therapeutic Communication, Non-Verbal Communication, and Overall Satisfaction ranged from 0.755 (P < 0.01) to 0.42 (P = 0.09). In this study, the results showed standardized patient evaluation has moderate to substantial reliability when compared to second raters of the same set of clinical encounters. This is similar to the reliability established over many decades of medical research. Greater use of this dynamic and interactive technique may be beneficial to nursing education and research. PMID- 22321161 TI - Obesity and erectile dysfunction of young men conscripted into the military in Taiwan. PMID- 22321162 TI - Hemiarthroplasty versus angle-stable locking compression plate osteosynthesis in the treatment of three- and four-part fractures of the proximal humerus in the elderly: design of a randomized controlled trial. AB - BACKGROUND: The optimal surgical management of dislocated three- and four-part fractures of the proximal humerus in elderly patients remains unclear. Most used techniques are hemiarthroplasty and angle-stable locking compression plate osteosynthesis. In the current literature there is no evidence available presenting superior results between hemiarthroplasty and angle-stable locking compression plate osteosynthesis in terms of speed of recovery, pain, patient satisfaction, functional outcome, quality of life or complications. METHODS/DESIGN: A randomized controlled multicenter trial will be conducted. Patients older than 60 years of age with a dislocated three- or four-part fracture of the proximal humerus as diagnosed by X-rays and CT-scans will be included. Exclusion criteria are a fracture older than 14 days, multiple comorbidity, multitrauma, a pathological fracture, previous surgery on the injured shoulder, severely deranged function caused by a previous disease, "head split" proximal humerus fracture and unwillingness or inability to follow instructions. Participants will be randomized between surgical treatment with hemiarthroplasty and angle-stable locking compression plate osteosynthesis. Measurements will take place preoperatively and 3 months, 6 months, 9 months, 12 months and 24 months postoperatively. Primary outcome measure is speed of recovery of functional capacity of the affected upper limb using the Disabilities of Arm, Shoulder and Hand score (DASH). Secondary outcome measures are pain, patient satisfaction, shoulder function, quality of life, radiological evaluation and complications. Data will be analyzed on an intention-to-treat basis, using univariate and multivariate analyses. DISCUSSION: Both hemiarthroplasty and angle stable locking compression plate osteosynthesis are used in the current treatment of dislocated three-and four-part fractures of the proximal humerus. There is a lack of level-1 studies comparing these two most-used surgical treatment options. This randomized controlled multicenter trial has been designed to determine which surgical treatment option provides the fastest recovery of functional capacity of the affected upper limb, and will provide better outcomes in pain, satisfaction, shoulder function, quality of life, radiological evaluation and complications. TRIAL REGISTRATION NUMBER: The trial is registered in the Netherlands Trial Registry (NTR2461). PMID- 22321163 TI - UK practice regarding reversal of vasectomy 2001-2010: relevance to best contemporary patient management. AB - Study Type - Practice trends (survey) Level of Evidence 2c What's known on the subject? and What does the study add? Approximately 6% of men who have had a vasectomy subsequently decide to have it reversed. For such men there are various options available, including vasal reconstruction, surgical sperm retrieval with assisted reproductive techniques, use of donated sperm or adoption. The decision making process with regard to the most appropriate management is challenging and the urologist requires both an intimate knowledge of the advantages and disadvantages of each of the available options and the opportunity to counsel a couple appropriately. The study confirms that patient management after previous vasectomy is a complex process, demanding detailed knowledge about the availability and outcomes of alternatives to vasectomy reversal. It recommends that couples should not be seen by urologists with diverse interests but by those with appropriate knowledge of all of the factors influencing outcome and the available management options and their costs. Urologists should also have appropriate facilities to offer intra-operative demonstration of and, potentially, storage of sperm. OBJECTIVES: To review the management of men presenting for reversal of vasectomy amongst consultant members of the British Association of Urological Surgeons (BAUS) between 2001 and 2010. * To make recommendations for contemporary practice. SUBJECTS AND METHODS: Three consecutive questionnaire-based surveys were undertaken by BAUS consultant members in 2001, 2005 and 2010. * Standard questionnaires were sent on each occasion asking urologists about their counselling of couples regarding options in achieving a conception, expectation of outcome from reconstructive surgery and the techniques of vaso-vasostomy used. * In 2005 additional information was obtained about the availability of fertility treatments and sub-specialization of the urologist and in 2010 about the eligibility criteria for in-vitro fertilization (IVF) treatment and synchronous sperm retrieval. RESULTS: Overall there was a 47% response rate with >80% of respondents still performing vaso vasostomy. * More than 75% of respondents were doing <15 procedures a year and <50% of respondents counselled couples about other management options. * Only 41% gave their personalized outcomes from vaso-vasostomy, whilst >80% were using some form of magnification intra-operatively. * Members of the BAUS section of andrology were more likely to discuss options for becoming a parent and criteria for IVF treatment, to present their individualized outcomes from vaso-vasotomy and to carry out >15 procedures a year than urologists with no andrological affiliation. CONCLUSIONS: * Patient management after previous vasectomy is a complex process necessitating detailed knowledge concerning the availability and outcomes of alternatives to vaso-vasostomy. * Couples should not be seen by urologists with diverse interests but by those with appropriate knowledge of all of the factors influencing outcome. * Vaso-vasostomy should no longer be seen as a procedure within the remit of any adequately trained urologist but as one option to be considered by a sub-specialist with access to appropriate micro surgical training and assisted reproductive technologies. PMID- 22321164 TI - Mathematical review of the energy transduction stoichiometries of C(4) leaf photosynthesis under limiting light. AB - A generalized model for electron (e(-) ) transport limited C(4) photosynthesis of NAD-malic enzyme and NADP-malic enzyme subtypes is presented. The model is used to review the thylakoid stoichiometries in vivo under strictly limiting light conditions, using published data on photosynthetic quantum yield and on photochemical efficiencies of photosystems (PS). Model review showed that cyclic e(-) transport (CET), rather than direct O(2) photoreduction, most likely contributed significantly to the production of extra ATP required for the C(4) cycle. Estimated CET, and non-cyclic e(-) transport supporting processes like nitrogen reduction, accounted for ca. 45 and 7% of total photosystem I (PSI) e(-) fluxes, respectively. The factor for excitation partitioning to photosystem II (PSII) was ca. 0.4. Further model analysis, in terms of the balanced NADPH: ATP ratio required for metabolism, indicated that: (1) the Q-cycle is obligatory; (2) the proton: ATP ratio is 4; and (3) the efficiency of proton pumping per e(-) transferred through the cytochrome b(6) /f complex is the same for CET and non cyclic pathways. The analysis also gave an approach to theoretically assess CO(2) leakiness from bundle-sheath cells, and projected a leakiness of 0.07-0.16. Compared with C(3) photosynthesis, the most striking C(4) stoichiometry is its high fraction of CET. PMID- 22321165 TI - Bioenergy potential of the United States constrained by satellite observations of existing productivity. AB - United States (U.S.) energy policy includes an expectation that bioenergy will be a substantial future energy source. In particular, the Energy Independence and Security Act of 2007 (EISA) aims to increase annual U.S. biofuel (secondary bioenergy) production by more than 3-fold, from 40 to 136 billion liters ethanol, which implies an even larger increase in biomass demand (primary energy), from roughly 2.9 to 7.4 EJ yr(-1). However, our understanding of many of the factors used to establish such energy targets is far from complete, introducing significgant uncertainty into the feasibility of current estimates of bioenergy potential. Here, we utilized satellite-derived net primary productivity (NPP) data-measured for every 1 km(2) of the 7.2 million km(2) of vegetated land in the conterminous U.S.-to estimate primary bioenergy potential (PBP). Our results indicate that PBP of the conterminous U.S. ranges from roughly 5.9 to 22.2 EJ yr( 1), depending on land use. The low end of this range represents the potential when harvesting residues only, while the high end would require an annual biomass harvest over an area more than three times current U.S. agricultural extent. While EISA energy targets are theoretically achievable, we show that meeting these targets utilizing current technology would require either an 80% displacement of current crop harvest or the conversion of 60% of rangeland productivity. Accordingly, realistically constrained estimates of bioenergy potential are critical for effective incorporation of bioenergy into the national energy portfolio. PMID- 22321166 TI - The phenotypic and genetic assessment of protein C deficiency. AB - This paper outlines the methods and approaches used for the laboratory detection and investigation of protein C (PC) deficiency. It does not make recommendations as to which patients should have thrombophilia testing performed; this should be done in line with local guidance. Interpretation of PC level is complicated because level varies with age, and many conditions can cause acquired deficiency. Protein C is most usually measured by chromogenic assay as a part of the thrombophilia screen. There exists, however, a very small group of individuals with significant PC deficiency, in whom the chromogenic PC assay is normal. The coagulometric assay of PC is more sensitive to these rare defects, but these assays may lack specificity. Genetic analysis allows definitive diagnosis and may be useful in confirming that deficiency is inherited and not acquired and is particularly valuable in families with severe PC deficiency. PMID- 22321167 TI - Influence of chronic stress on the compositions of hepatic cholesterol and triglyceride in male Wistar rats fed a high fat diet. AB - AIM: We determined the influence of chronic stress (CS) on the compositions of hepatic cholesterol and triglyceride (TG) in rats fed a high fat diet (HFD). METHODS: Male Wistar rats were fed either a standard diet or a HFD and half of the HFD fed rats were given CS (electric foot shock assisted with noise) for 8 weeks. RESULTS: Compared with the control group, the levels of hepatic total cholesterol (TC) and TG were significantly elevated in the HFD and HFD with chronic stress (HFD+CS) groups, and the more severe elevations of them were found in the HFD group. Inversely, the more severe elevations of hepatic water-soluble parts of TC and TG were found in the HFD+CS group, as the elevations of low density lipoprotein cholesterol, very low-density lipoprotein cholesterol in liver and serum, tumor necrosis factor-alpha, interleukin-1beta and malondialdehyde in liver. Meanwhile, downregulated mRNA expressions of hepatic liver X receptor-alpha (LXR-alpha) and peroxisome proliferator-activated receptor gamma (PPAR-gamma) were also more severe in the HFD+CS group. CONCLUSION: CS can aggravate the high levels of water-soluble compositions of hepatic TC and TG induced by HFD as it aggravates hepatic inflammation and oxidative stress; in spite of that, however, it cannot further promote hepatic lipidosis. This is consistent with the downregulated mRNA expressions of LXR-alpha and PPAR-gamma. PMID- 22321168 TI - Aromatic characterization of pot distilled kiwi spirits. AB - This study contributes fundamental knowledge that will help to develop a distillate of kiwi wine, made from kiwis of the Hayward variety grown in the southwest of Galicia (Spain). Two yeast strains, L1 (Saccharomyces cerevisiae ALB 6 from the EVEGA yeast collection) and L2 (S. cerevisiae Uvaferm BDX from Lallemand) were assessed to obtain a highly aromatic distillate. The kiwi spirits obtained were compared with other fruit spirits, in terms of higher alcohols, minor alcohols, monoterpenols, and other minor compounds, which are relevant in determining the quality and taste of the kiwi spirits. It was found that the kiwi juice fermented with yeast L1 produced a more aromatic distillate. In addition, kiwi distillates produced with both yeasts had the same ratio of trans-3-hexen-1 ol and cis-3-hexen-1-ol, which is lower than that found in other fruit distillates. PMID- 22321169 TI - Glucose control in diabetes: which target level to aim for? AB - The most important goal in the treatment of patients with diabetes is to lower the risk of long-term diabetes complications. Hyperglycaemia is the most important risk factor for microvascular complications in diabetes, but, in addition to hyperglycaemia, several other risk factors, particularly dyslipidaemia, elevated blood pressure and smoking, also determine the risk of macrovascular complications. In this review, we present evidence from longitudinal population-based studies that hyperglycaemia is an important risk factor for long-term complications of diabetes and discuss the results from clinical trials of the effects of the treatment of hyperglycaemia on the prevention of long-term micro- and macrovascular complications in type 1 and type 2 diabetes. An HbA(1c) target of <7.0% for the treatment of diabetes is generally accepted on the basis of evidence from several trials, whereas a target of <6.5% may be reasonable for patients with a short duration of type 2 diabetes and without extensive atherosclerosis. PMID- 22321170 TI - Effect of ZnO nanoparticle properties on dye-sensitized solar cell performance. AB - We have investigated the effect of ZnO nanoparticle properties on the dye sensitized solar cell performance. Nanoparticles with different sizes and optical properties were considered. We found that there is a complex relationship between native defects, dye adsorption, charge transport and solar cell performance. The presence of a high concentration of nonradiative defects was found to be detrimental to photovoltaic performance, whereas for radiative defects, samples displaying orange-red defect emission exhibited better performance compared to samples with green defect emission (when the samples had similar emission intensities). Detailed discussion of the nanoparticle properties and their relationship with dye adsorption, electron injection, electron lifetime, electron transport time, and solar cell performance is given. PMID- 22321171 TI - Under-representation of repetitive sequences in whole-genome shotgun sequence databases: an illustration using a recently acquired transposable element. AB - It is widely accepted in a conceptual framework that repetitive sequences, especially those with high sequence homogeneity among copies, tend to be under represented in whole-genome shotgun sequence databases, because of the difficulty of assembling sequence reads into contigs. Although this is easily inferred, there is no quantitative illustration of this phenomenon. An example using a currently used database is expected to contribute to the intuitive understanding of how serious the under-representation is. The present study provides the first quantitative example (in the case of 16 copies of virtually identical, 4.7-kb sequences in a genome of 7 * 10 (8) bp) by comparing the results of BLAST searches of a sequence database (contig N50; 9.8 kb) with those of Southern blot analysis of genomic DNA. This has revealed that the internal regions of the repetitive sequences are under-represented to a striking extent. PMID- 22321172 TI - Testing benthic foraminiferal distributions as a contemporary quantitative approach to biomonitoring estuarine heavy metal pollution. AB - Biomonitoring of estuarine pollution is the subject of active research, and benthic foraminifera are an attractive group to use for these purposes due to their ubiquitous presence in saline water and wide diversity. Here, we describe a case study of biomonitoring using benthic foraminifera in the French Mediterranean lagoon, Bages-Sigean lagoon. In this case, the major pollutants of interest are heavy metals in the sediment, particularly contaminated by Cu and Cd derived from industrial and agricultural sources. The foraminiferal assemblages of the Bages-Sigean lagoon are typical of normal paralic environments, but unusually almost completely lack agglutinated forms. The density of benthic foraminifera was shown to be more influenced by the sediment characteristics rather than heavy metal pollution. However, the relative abundance of Quinqueloculina bicostata was shown to increase in the most polluted areas and we propose that this taxon may be used as an indicator of heavy metal pollution. PMID- 22321173 TI - Antibiotic resistant pathogens versus human impacts: a study from three eco regions of the Chennai coast, southern India. AB - We assessed the occurrence of pollution indicators and antibiotic resistant bacterial isolates from water and sediment samples of three different eco-regions of the Chennai coast between March - May of 2010. Total of 960 bacterial strains belonging to four genera were isolated which show the highest frequencies of resistance to vancomycin (53.6%) and penicillin (52.6%) (except Enterococcus sp., which is highly resistant to erythromycin) and lowest frequencies of resistance to chloramphenicol (3.43%), ciprofloxacin (3.95%), gentamicin (4.68%), and tetracycline (6.97%). The E. coli, Vibrio sp., Salmonella sp. and Enterococcus sp. show high frequency of resistance to 2-5 antibacterials of 60.4%, 45.83%, 69.16% and 46.6%, respectively. High pollution indices (PI - 6.66-14.06) and antibiotic resistance indices (ARI - 0.29-0.343) indicate that the coastal environment is highly exposed to antibiotic sources that suggesting to avoid direct contact. PMID- 22321174 TI - [Focus on the diagnosis of interstitial lung diseases in children]. PMID- 22321175 TI - [Present status of research on bronchiolitis obliterans in children]. PMID- 22321176 TI - [Pay attention to birth defect disorders associated with maternal nutrition]. PMID- 22321177 TI - [Clinical study on interstitial lung disease in children of China]. AB - OBJECTIVE: Interstitial lung disease in children represents a heterogeneous group of disorders of both known and unknown causes. This study aimed to understand better the causes of the disease in children and to provide information on the current approach to diagnosis and management of the disease. METHOD: Through the Pediatric Diffuse Parenchymal Lung Disease/Pediatric Interstitial Lung Disease Cooperative Group of China, data of 93 cases of interstitial lung disease of children from 11 hospitals were collected with the same questionnaire in 2009. Respiratory tract secretions were obtained for bacterial culture. Respiratory virus antigen examination, mycoplasma antibody, EB virus, cytomegalovirus, and herpes simplex viruses antibody detection were performed. Cells in the sputum, gastric juice and bronchoalveolar lavage fluid (BALF) were tested for hemosiderin. The CT or high resolution CT (HRCT) of the lung and blood-gas analysis were also performed. Fourteen cases underwent lung biopsy and 25 cases underwent bronchomicrocopy. Data were then pooled and discussed through a series of meetings. RESULT: Fifty-three cases were male, 40 were female and their age ranged from 8 months to 14 years. Thirty-nine cases were diagnosed as bronchiolitis obliterans (BO); 39 as idiopathic pulmonary hemosiderosis (IPH); 7 as idiopathic interstitial pneumonia (IIP) of unknown causes, of whom 4 cases had non specific interstitial pneumonia, 1 case as acute interstitial pneumonia and 1 case as lymphocytic interstitial pneumonia, 1 case as idiopathic pulmonary fibrosis; 2 cases as secondary interstitial lung disease, one was secondary to SLE, one to human immunodeficiency virus (HIV) infection; 2 cases had hypersensitive pneumonitis; 2 cases had pulmonary alveolar proteinosis; 1 case had bronchiolitis obliterans organizing pneumonia; 1 case had lipoid pneumonia;1 case of diffuse panbronchiolitis; 1 case of microlithiasis alveolaris pulmonum. Forty two cases had cough, 24 of them also had tachypnea, 8 cases had clubbing. HRCT showed that 56 cases had groundglass-like opacification; 30 cases had mosaic appearance; 1 case had diffuse micronodular opacities, 1 case had diffuse reticulonodular opacities and cysts. CONCLUSION: Interstitial lung disease in children is a heterogeneous group of disorders. In this study diagnoses of 11 diseases were made, the top third diagnoses were BO, IPH and IIP, respectively. PMID- 22321178 TI - [Questionnaire-based survey of allergic diseases among children aged 0 - 14 years in the downtown of Beijing, Chongqing and Guangzhou]. AB - OBJECTIVE: In recent years, the incidence of allergic diseases in China is increasing. With serious influence on the patients' quality of life and even life threatening, now allergic diseases have become an important public health problem in our country. This survey aimed to obtain a general epidemic outline of children's major allergic diseases, i.e., childhood asthma, allergic rhinitis and eczema in the downtown of Beijing, Chongqing and Guangzhou. METHOD: Childhood asthma questionnaire was established by Delphi method based on guidelines for childhood asthma diagnosis and prevention made by Chinese medical association in 2008 with reference to the International Study of Asthma and Allergies in Childhood questionnaire (ISAAC). This study was carried out from Oct. 2008-Mar. 2009, in Beijing, Chongqing and Guangzhou by a multi-stage sampling method, covering a sample of 24 290 children aged 0 - 14 years by a multi-stage sampling method, the population of children surveyed in the downtown of Beijing Chongqing and Guangzhou was 10 372, 9874 and 4072 respectively; of whom males were 5545, 5258, 2159, and females were 4917, 4588, 1877; the ratio of males to females in the three cities were 1.11:1, 1.15:1, 1.15:1; the average age of surveyed children were 7.63, 8.74 and 8.30 years old. All the questionnaire was filled in by the parents of children or other guardian of children. RESULT: The self reported prevalence of asthma in Beijing, Chongqing and Guangzhou was 3.15%, 7.45%, 2.09%, the self-reported prevalence of allergic rhinitis was 14.46%, 20.42%, 7.83%, and the prevalence of eczema was 20.64%, 10.02%, 7.22%. In the survey, asthma combined with allergic rhinitis had the highest rate, 49.54%, 50.14%, 34.83%, respectively in the 3 cities. The self-reported prevalence of asthma and allergic rhinitis was significantly higher in male than female. Besides, the self-reported prevalences of asthma and allergic rhinitis were relatively lower in children under 1 year and over 10 years of age. CONCLUSION: The prevalence of asthma, allergic rhinitis and eczema and other allergic diseases in children 0 - 14 years of age in the three cities gradually increased, and the prevalence of allergic diseases in Chongqing was relatively higher. PMID- 22321179 TI - [Three years surveillance of viral etiology of acute lower respiratory tract infection in children from 2007 to 2010]. AB - OBJECTIVE: Viruses are common pathogens of acute lower respiratory tract infection (ALRTI) in children. There are few studies on consecutive monitoring of viral pathogens of ALRTI in a larger cohort during the past several years. The aim of this study was to investigate the viral pathogens of ALRTI in children of different age groups and to outline the epidemic feature of different viruses. METHOD: (1) Totally 1914 (1281 male and 709 female) children with clinical diagnosis of ALRTI during the period of March 2007 to March 2010 were recruited into this study. These patients were hospitalized patients in department of internal medicine or outpatients in emergency department in Beijing Children's Hospital. The patients were divided into four groups, including 1072 patients < 1 year old, 326 patients 1- < 3 years old, 158 patients 3- < 6 years old, 358 patients >= 6 years old. One nasopharyngeal aspirate specimen was collected from each patient. Reverse transcription (RT) PCR methods were applied to detect common respiratory viruses including respiratory syncytial virus (RSV), human rhinovirus (HRV), influenza virus type A, B and C (IFA, IFB, IFC), parainfluenza virus (PIV) type 1-4, adenovirus (ADV), enterovirus (EV), human coronavirus (HCOV), human metapneumovirus (HMPV) and human bocavirus (HBOV). RESULT: (1) The total positive rate of viruses was 70.3%. The positive rate was 83.0% (890/1072) in the group of < 1 year old, and 80.1% (261/326) in group of 1- < 3 years old, 60.8% (96/158) in group of 3- < 6 years old and 27.7% (99/358) in group of >= 6 years old, respectively. There was a significant difference in the positive rate among different age groups (chi2 = 2213.5, P = 0.000). The top three viruses were RSV, HRV and PIV; and the positive rates were 50.9%, 36.2% and 12.0% respectively in group of < 1 year old. (2) The epidemic seasons of RSV and HRV were winter and spring, and PIV infection was epidemic in spring and summer. (3) The detection rates of 2 or more viruses were 38.2%, 36.4%, 30.2% and 15.2% in groups of < 1 year old, 1- < 3 years old, 3- < 6 years old and >= 6 years old, respectively. There was a significant difference in the mixed infection rate among different age groups (chi2 = 1346.00, P = 0.000). CONCLUSION: RSV, HRV and PIV were the most predominant pathogens in younger children with ALRTI. Different viral infections had different seasonal features. Mixed infections with two or more viruses were detected in substantial proportion of patients with ALRTI, but further studies are needed to explore the clinical significance of mixed infection with viruses in patients with ALRTI. PMID- 22321180 TI - [Genotyping of Mycoplasma pneumoniae in nasopharyngeal aspirate from children with pneumonia in Zhejiang Province]. AB - OBJECTIVE: The P1 protein of Mycoplasma pneumoniae (MP) plays an important role in the pathogenesis of MP pneumonia. It mediates the attachment of the pathogen to host cells and elicits a strong humoral immune response during infection. In early studies, only two types of MP P1 genes were assumed to exist. Later, eight subtypes of MP P1 genes and some variations of P1 gene were reported. However, there are no related reports in China until now. This study aimed to understand epidemiology of MP subtype in Zhejiang province, China, as well as the relationship between MP subtype and clinical severity of MP pneumonia. METHOD: Clinical samples were collected by nasopharyngeal aspiration from children with MP pneumonia hospitalized in the Children's Hospital of Zhejiang University School of Medicine from February to December in 2009. P1 gene fragment was amplified by using PCR method (with primers of ADH1/ADH2 and ADH3/ADH4, respectively). Then ADH1/ADH2-generated fragments were digested with HaeIII, HpaII, Sau3A, and the ADH3/ADH4-generated fragments digested with HaeIII, Sau3A, HhaI, RsaI. The MP P1 subtypes were determined based on resulting fragments. Part of samples were selected for sequencing. The clinical data of different MP subtype pneumonia were compared. RESULT: A total of 300 hospitalized children with MP pneumonia were enrolled in this study. All the samples produced specific bands for MP P1 gene after PCR with primers of ADH1/ADH2 and ADH3/ADH4 respectively. By restrictive fragment length polymorphism analysis, 297 clinical specimens showed the characteristic band patterns for P1 type 1 identical to Mp129, and only 3 clinical specimens showed the characteristic band pattern for P1 type 2 identical to MP-FH. All P1 type 1 and P1 type 2 showed the same subtype bands respectively, as subtype 1b and 2a. After sequencing, one synonymous point mutation in P1 type 1 was identified relative to the MP129 P1 sequence at nucleotide position (nt) 208(G->A). Three cases with P1 type 2 MP pneumonia were found to have liver damage, and longer hospital stay and fever duration than P1 type 1, but no statistically significant difference was found. CONCLUSION: Clinical samples can be used directly for genotyping of MP. The dominating type of MP in Zhejiang Province was P1 type 1 subtype 1b. But whether there was any relationship between MP subtype and clinical severity remains to be clarified. PMID- 22321181 TI - [Value of exhaled nitric oxide in diagnosis and management of asthma]. PMID- 22321182 TI - [Erythropoietin and neonatal brain injury]. PMID- 22321183 TI - [Closing ductus treatments of patent ductus arteriosus in preterm infants]. PMID- 22321184 TI - [Screening for neonatal inborn errors of metabolism by electrospray ionization tandem mass spectrometry and follow-up]. AB - OBJECTIVE: To determine the impact of expanded newborn screening using tandem mass spectrometry (MS/MS) on the overall detection rate of inborn errors of metabolism in Zhejiang province and to assess the outcome of the patients who were diagnosed. METHOD: Blood spots were collected between days 3 and 6 of life from the newborns. All samples were subjected to MS/MS analysis using Waters Quattro API. Confirmation tests included amino acid analysis, urinary organic acids by GC-MS, routine blood analysis, biochemistry, blood gas analysis, blood glucose and ammonia tests, blood homocysteine, lactate and pyruvate tests, urine acetone tests, biotin and biotin enzyme profile and DNA analysis. Standard treatment protocol was given to the patients. Protein restricted diet, special powdered formula and medicines recommended for the patients with amino acidemias. Protein restricted diet and L-carnitine, folic acid and Vitamin B12 supplementation were given for the patients with organic acidemia. L-carnitine was given to the patients with primary carnitine deficiency. The overall epidemiology, prognosis, follow-up of the screening program were also investigated in the neonates. RESULT: A total of 129 415 neonates were investigated for 26 inborn errors of metabolism during the period. Twenty-three newborns were confirmed as having inborn errors of metabolism, including 13 with amino acidemias, 6 with organic acidemias and 4 with fatty acid oxidation disorders. The prevalence was 1:5626. Positive predictive value was 2.10%, specificity was 99.72% and sensitivity 100%. Seventeen children remain asymptomatic during the follow-up. Five patients had motor and mental developmental delay. One patient presented metabolic disorders during the follow up. No death occurred in this series of patients. CONCLUSION: This strategy represents a valuable preventive medicine approach by enabling diagnosis and treatment before the onset of symptoms. PMID- 22321185 TI - [Effect of aggressive nutritional support on preterm infants during hospitalization]. AB - OBJECTIVE: To explore the effect of aggressive nutritional support in early life on growth of preterm infants during hospitalization. METHOD: Two retrospective cohorts of preterm infants were compared; 81 infants of group A (born between January 1, 2005 and June 30, 2006) and 79 infants of group B (June 1, 2009 and November 30, 2010) with gestational age above 28 weeks and birth weight between 1000 g and 2000 g, transfered to NICU of PUMCH within 12 hours after birth, hospitalized for > or = 2 weeks, who were free of major congenital anomalies and survived to discharge were recruited. The comparison of enteral and parenteral nutrition, growth rate, biochemical indices during hospitalization between these both groups were made. RESULT: Compared to group A, group B was given greater volume of amino acid infusion on the 3(rd) and 7(th) day of life [2.00 (2.00, 2.50) g/kg vs 1.50 (1.50, 2.00) g/kg, 3.00 (2.00, 3.00) g/kg vs 2.00 (1.80, 2.60) g/kg, all P < 0.001], and Consumed more milk and total energy intake on the 3rd day of life [9.41(2.66, 18.74) ml/kg vs 14.47 (4.23, 30.77) ml/kg, P < 0.05, (64.87 +/- 16.04) kcal/kg vs (55.62 +/- 17.68) kcal/kg, P = 0.001]. Total energy intakes after a week of life were similar between the two groups. More infants received human milk fortifier in group B (62.8% vs 14.3%, P = 0.001). After stratification according to weight, both very low birth weight infants and infants with birth weight between 1500 g and 2000 g in group B grew more rapidly (P < 0.001). The percentage of growth retardation was increased after hospitalization in group A (65.4% vs 40.7%, P < 0.05), there were no statistically significant differences in group B. The mean Z scores at birth were comparable. The mean Z scores by discharge were higher in group B (-1.24 vs 1.54, P < 0.05). Serum albumin, prealbumin and urea values were similar in both groups at birth, but higher in group B after two weeks of life (P < 0.001). Before discharge, Serum albumin, prealbumin, and urea values in group B was higher (P < 0.001). CONCLUSION: Improvements in nutritional practices in early life of preterm infants effectively enhanced the growth and improved the nutritional status of preterm infants during hospitalization. PMID- 22321186 TI - [Effects of sodium valproate on neutrophils' oxidative metabolism and oxidant status in children with idiopathic epilepsy]. AB - OBJECTIVE: To evaluate the influence of VPA treatment on neutrophils' oxidative metabolism and oxidant status in epileptic children. METHOD: Twenty-six newly diagnosed epileptic children with idiopathic epilepsy and 30 healthy children were included in the study. The activation rates of neutrophils and stimulation indexes were detected in patients before and 6 months and 12 months after VPA treatment respectively and in all the healthy children by flow cytometry with dihydrorhodamine as fluorochrome. The activities of myeloperoxidase from neutrophils were also detected. Malondialdehyde as an indicator of lipid peroxidation and antioxidant enzymes including superoxide dismutase, catalase, and glutathione peroxidase were measured in plasma respectively. RESULT: The activation rates of neutrophils in patients treated with VPA after 6 and 12 months were (11.50 +/- 6.52)% and (14.31 +/- 5.76)% respectively, which were significantly higher than the data of control group (5.90 +/- 3.77)% and pretreatment level (7.42 +/- 3.15)%. The stimulation indexes 6 and 12 months after VPA therapy were (474.88 +/- 118.98) and (416.31 +/- 110.00) respectively, which were lower than the data of control group (544.83 +/- 140.83) and pretreatment level (535.23 +/- 111.55). The plasma MPO activities and levels of malondialdehyde in VPA treated patients were also higher while the activities of SOD and CAT were significantly lower than the control and untreated groups. GSH Px levels did not differ between the groups. Multiple linear regression analysis showed that the time of treatment and the activation rates of neutrophils were indicators which had positive correlation with the levels of plasma MDA and that SOD activities were inversely correlated with MDA levels. CONCLUSION: VPA which is frequently used in childhood epilepsy may activate the neutrophils of patients and cause oxidative stress and prolonged treatment may aggravate it. PMID- 22321187 TI - [Experimental study on expression of connective tissue growth factor in viral myocarditis in mice]. AB - OBJECTIVE: To study the expression of connective tissue growth factor (CTGF) in the myocardial tissue of mice with viral myocarditis (VMC). METHOD: Balb/c mice were infected with coxsackie virus B3 (CVB3) to establish VMC model. The mice were divided into control group (n = 50) and VMC group (n = 50). on days 4, 7, 14 and 21 after infection, heart specimens of 8 mice were randomly taken and examined after HE staining for myocardial necrosis and cellular infiltration. The area of positive Masson stained myocardium collagen fibers was measured, and collagen volume fraction (CVF) was measured. Then the level of serum creatine phosphokinase-MB (CKMB) was determined. The levels of CTGF and TGF-beta1 were detected by streptavidin peroxidase immunoperoxidase technique. Expression of CTGF and TGF-beta1 were detected with reverse transcription-polymerase chain reaction (RT-PCR). At the same time, the correlations were analyzed. RESULT: (1) The level of CKMB peaked on day 7, and decreased afterwards (455.45 +/- 37.95, 606.95 +/- 35.64, 573.62 +/- 42.90, 308.60 +/- 20.49, respectively, 4 - 21 d points), in which 4, 7, 14 d points, there was significant difference compared with control group (t = 6.144, 12.558, 11.182, respectively, P < 0.01). (2) CVF increased significantly on day 14 (8.22 +/- 1.95, t = 4.486, P < 0.01) and day 21 (9.46 +/- 1.87, t = 4.486, P < 0.01) in VMC group. (3) Measured by streptavidin peroxidase immunoperoxidase technique, the levels of CTGF (171.50 +/- 10.25, 141.70 +/- 10.863, 110.35 +/- 11.051, 81.05 +/- 10.190, respectively, 4 - 21 d points) and TGF-beta1 (184.90 +/- 11.480, 150.25 +/- 9.915, 103.50 +/- 10.455, 84.15 +/- 9.848, respectively, 4 - 21 d points) increased after day 4 in VMC (P < 0.01). (4) Measured by RT-PCR, the expression of CTGF mRNA and TGF-beta1 increased in VMC group, and the increase was enhanced with the disease development (P < 0.01). (5) The expression of CTGF and TGF-beta1 was positively linearly correlated (r = 0.987, P < 0.01), the expression of CTGF was negatively correlated with CVF (r = -0.901, P < 0.01), but the expression of CTGF was detected earlier than myocardial fibrosis. CONCLUSION: The increase of CTGF expression was associated with the severity of myocardial fibrosis in VMC. These results suggest that abnormal expression of CTGF may take part in the development of fibrosis in VMC. PMID- 22321188 TI - [Clinical analysis of 8 cases with acute invasive pulmonary aspergillosis in younger children]. AB - OBJECTIVES: To analyze the clinical features of acute invasive pulmonary aspergillosis in younger children, in order to improve the levels of early recognition, diagnosis and management of this disease. METHOD: Clinical data of 8 patients aged below 15 months who were diagnosed as acute invasive pulmonary aspergillosis from August 2010 to February 2011 in general pediatric wards in our hospital were retrospectively analyzed for the high-risk factors of the hosts, clinical manifestations, laboratory findings and lung CT imaging, the processes of diagnosis and treatment, and the outcomes. RESULT: Five cases were tested for serum GM test absorbent index (GMI) ranged from 1.92 to 3.27; in 2 cases sputum culture was positive for Aspergillus fumigatus for twice, and 1 infant was serum GMI 2.85 and a sputum culture was positive for Aspergillus fumigatus positive, all these findings were accordant with the clinical diagnosis. Seven cases had a history of receiving intravenously broad-spectrum antibiotics or plus corticosteroids (6 hospitalized, 1 out-patient), and one was only 1 month old, whose parents had severe tinea pedis. 4 patients of high-fever type had sustained high temperature, severe changes of lungs without obvious respiratory symptoms and signs in early phase, and significant increase of the rod granulocyte rate (0.25 - 0.68), which was apparently discordant with the normal WBC count and high sensitivity C-reactive protein (hs-CRP) value. Another 4 cases of non-high-fever type were present with normal WBC count, hs-CRP value and the percentage of rod granulocyte. Among them, 3 infants had low-grade fever, with serious respiratory symptoms and signs and changes of lungs CT. Another 1-month-old case only showed lower vigor and response. Lung CT imaging often showed multiple irregular large nodules, patches and streaks of density (6 cases) and unilateral lobar consolidation (1 case), with some involving the pleura; one appeared severe peri main bronchus lesions with stenoses of bilateral main bronchi. The first case died of multiple organ failure because of severe sepsis complication. Another 7 cases were treated with voriconazole promptly after clinical or suspected diagnosis, and the state of patients relieved rapidly within 1 - 3 d. CONCLUSION: The abuse of broad-spectrum antibiotics and corticosteroids may increase the risk of invasive pulmonary aspergillosis in younger children. There may be the risk of nosocomial infection and spread of aspergillus in general pediatric wards. Cases of high-fever type in early period of disease had two inconsistency: few symptoms and signs, while severe changes of lungs CT; apparent increase of peripheral rod granulocyte, while normal WBC count and hs-CRP value. Preemptive voriconazole therapy could obtain significant effect and reduce the mortality rate. PMID- 22321189 TI - [Clinical characteristics and changes in blood electrolyte and renal function of neonates with polycythemia at high altitude]. AB - OBJECTIVE: To analyze the relationship between neonatal hypoxia and polycythemia and to study clinical characteristics of Tibetan neonates whose family lived in Tibetan plateau for generations and Han neonates whose family moved to the plateau. METHOD: From Jan. 2005 to Oct. 2006, totally 739 patients were hospitalized in the ward of neonatology of the hospital. Of these patients, 40 (20 were Tibetan and the other 20 were Han) with neonatal polycythemia. The clinical features, transcutaneous oxygen saturation (TcSO2), peripheral routine tests and myocardial enzyme profile were studied. RESULT: The values of hemoglobin (Hb), hematocrit (HCT), and erythrocyte count (RBC) of the Han neonates were significantly higher than those of the Tibetan newborns. Han neonates with polycythemia had lower TcSPO2 than Tibetan neonates (P < 0.01). Comparison of myocardial enzymes showed that Han neonates had higher CKMB than that of Tibetan groups before treatment (P < 0.01), troponin was not significantly different between the Han and Tibetan groups before treatment (P > 0.05). The major common clinical manifestations of the Han and Tibetan newborns were tachypnea, cyanosis, irritability, weak reflexes and hypoxemia. The Han neonates additionally had poor responses, apnea, lower muscle tone, confusion and asphyxia. CONCLUSION: The clinical characteristics, TcSO2, peripheral blood routine tests and myocardial enzyme profile are helpful in diagnosis and treatment of neonatal polycythemia. Newborn infants born to mothers who moved to the plateau area may be more susceptible to neonatal polycythemia and are prone to impairments of other organs, esp. the functions of the heart and brain. PMID- 22321190 TI - [Neonatal withdrawal syndrome associated with maternal clozapine and haloperidol therapy]. PMID- 22321191 TI - [Chronic active EBV infection complicated with EBV-related central nervous system T-cell proliferative diseases: report of a case with five-year follow-up]. PMID- 22321192 TI - [Disinfectant-induced irritating cough in a child]. PMID- 22321193 TI - Papillary fibroelastoma of the aortic valve with atypical chest pain: late presentation with acute myocardial infarction and cardiac arrest. AB - We report a case of a 54-year-old female with papillary fibroelastoma of the aortic valve who presented with ST-elevation myocardial infarction and cardiac arrest. Though her initial symptom was only atypical chest pain, life-threatening complications such as acute myocardial infarction and cardiac arrest developed. After cardiopulmonary resuscitation, we promptly resected the fibroelastoma on cardiopulmonary bypass, and the patient was discharged without any other complications. PMID- 22321194 TI - beta-Amyloid exacerbates inflammation in astrocytes lacking fatty acid amide hydrolase through a mechanism involving PPAR-alpha, PPAR-gamma and TRPV1, but not CB1 or CB2 receptors. AB - BACKGROUND AND PURPOSE: The endocannabinoid system may regulate glial cell functions and their responses to pathological stimuli, specifically, Alzheimer's disease. One experimental approach is the enhancement of endocannabinoid tone by blocking the activity of degradative enzymes, such as fatty acid amide hydrolase (FAAH). EXPERIMENTAL APPROACH: We examined the role of FAAH in the response of astrocytes to the pathologic form of beta-amyloid (Abeta). Astrocytes from wild type mice (WT) and from mice lacking FAAH (FAAH-KO) were incubated with Abeta for 8, 24 and 48 h, and their inflammatory responses were quantified by elisa, western-blotting and real-time quantitative-PCR. KEY RESULTS: FAAH-KO astrocytes were significantly more responsive to Abeta than WT astrocytes, as shown by the higher production of pro-inflammatory cytokines. Expression of COX-2, inducible NOS and TNF-alpha was also increased in Abeta-exposed KO astrocytes compared with that in WTs. These effects were accompanied by a differential pattern of activation of signalling cascades involved in mediating inflammatory responses, such as ERK1/2, p38MAPK and NFkappaB. PPAR-alpha and PPAR-gamma as well as transient receptor potential vanilloid-1 (TRPV1), but not cannabinoid CB1 or CB2 receptors, mediate some of the differential changes observed in Abeta-exposed FAAH-KO astrocytes. The pharmacological blockade of FAAH did not render astrocytes more sensitive to Abeta. In contrast, exogenous addition of several acylethanolamides (anandamide, palmitoylethanolamide and oleoylethanolamide) induced an antiinflammatory response. CONCLUSIONS: The genetic deletion of FAAH in astrocytes exacerbated their inflammatory phenotype against Abeta in a process involving PPAR-alpha, PPAR-gamma and TRPV1 receptors. PMID- 22321195 TI - Maternal resveratrol treatment during pregnancy improves adverse fetal outcomes in a rat model of severe hypoxia. AB - Prenatal hypoxia is a common complication in pregnancy. We sought to determine whether resveratrol, a phytoalexin shown to improve health in several species, improves fetal outcomes associated with prenatal hypoxia in rats. Supplementation of maternal diets with resveratrol (4 g/kg diet) from gestational day (GD) 7 to GD21 almost completely reversed fetal demise in hypoxic (8.5% oxygen) pregnancies. We also show that resveratrol crosses the placenta, and may affect the fetus directly. PMID- 22321196 TI - Blood salvage and cancer surgery: a meta-analysis of available studies. AB - BACKGROUND: Intraoperative blood salvage (IBS) is a technique that is frequently used in major blood loss surgery. Classically, it is avoided during cancer surgery where a fear exists of entraining cancer cells into the shed blood. In this study, all reports of this practice were collected to determine if this fear is warranted. STUDY DESIGN AND METHODS: A literature search was performed including the search phrases "blood salvage,""intraoperative blood salvage,""cell salvage,""cell saver,""cell saving,""autotransfusion," and "autologous transfusion." Data extracted from suitable papers included the authors' names, publication year, cancer type, exclusion criteria, sample size, length of follow up, and the mean patient age. The primary endpoint of this meta-analysis was a comparison of the odds ratio (OR) for cancer recurrence or the development of metastases. RESULTS: Eleven studies were included in the analysis. The pooled summary of the OR was 0.65 (95% confidence interval, 0.43-0.98; p = 0.0391) using a random-effects model. Measures of heterogeneity, Q-statistics (p= 0.1615) and I(2) (30.90%), did not indicate a high degree of between-study variability. CONCLUSIONS: While significant variability existed between studies, this meta analysis suggests that outcomes after the use of IBS are not inferior to traditional intraoperative allogeneic transfusion. An adequately powered prospective, randomized trial of IBS use is required to determine its true risk during cancer surgery. PMID- 22321197 TI - The ethnic divide in breast reconstruction: a review of the current literature and directions for future research. AB - Ethnic disparities exist in many areas of breast cancer treatment. When a mastectomy is necessary, the next discussion in the overall surgical management often focuses on breast reconstruction. This review will examine breast reconstruction trends within different ethnic groups and will briefly discuss underlying factors influencing current disparities. The literature available on differences in breast reconstruction loosely fits into two general categories: (1) the decision making process for reconstruction and (2) the receipt, timing and type of breast reconstruction. This review will seek to highlight several areas for possible intervention as well as areas where further research is needed. PMID- 22321198 TI - Measuring substance use in the club setting: a feasibility study using biochemical markers. AB - BACKGROUND: During the last few decades the use of club drugs (e.g., cocaine, amphetamines) has been of increased concern in nightlife settings. Traditionally, surveys have been used to estimate the use of club drugs, however, they mostly rely on self-reports which may not be accurate. Recent advances have allowed for readily accessible drug testing methods such as oral fluid drug testing. Nevertheless, research using oral fluid sampling to measure the frequency of drug use in the club environment is scarce. The objective of this study is to evaluate the feasibility of measuring the frequency of alcohol and drug use among Swedish clubbers using breath alcohol and oral fluid drug testing. METHOD: The setting was a 40 hour electronic music dance event (EMDE) on a cruise ship on the Baltic Sea, departing from Sweden, with 875 passengers. Groups of participants at the EMDE were randomly invited to participate. Data were collected with face-to-face and self-administered questionnaires. Further, oral fluid samples were collected to determine illicit drug use, and blood alcohol concentration (BAC) levels were measured using a breath analyzer. RESULTS: A total of 422 passengers were asked to participate in the study whereof 21 declined (5.0% refusal rate). Of the 401 study participants (accounting for 45.8% of all attendees), 5 declined oral fluid drug testing. Results show that there was a discrepancy between self-reported and actual drug use as 10.1% of the participants were positive on illicit drug use (amphetamines, ecstasy/MDMA, cannabis, cocaine), while only 3.7% of the participants reported drug use during the last 48 hours. The average BAC level was 0.10% and 23.7% had BAC levels >= 0.15%, while 5.9% had levels below the detection limit. The mean BAC levels for the illicit drug users were significantly higher (p = 0.004) than for non-drug users (0.13% vs. 0.10%). Self reported AUDIT-C scores (using a threshold of >= 5 for men and >= 4 for women) revealed that 76.0% of the men and 80.7% of the women had risky alcohol consumption patterns. CONCLUSION: This study indicates that it is feasible to conduct breath alcohol and oral fluid drug testing in a Swedish club setting. PMID- 22321199 TI - A score that verifies adherence to a gluten-free diet: a cross-sectional, multicentre validation in real clinical life. AB - A dietary interview performed by expert personnel is the best method to check whether patients with coeliac disease follow a strict gluten-free diet (GFD). We previously developed a score based on four fast and simple questions that can be administered even by non-expert personnel. The aim of the present study is to verify the reliability of our questionnaire in a new cohort of patients. The questionnaire has a five-level score. From March 2008 to January 2011, the questionnaire was administered to 141 coeliac patients on a GFD, who were undergoing re-evaluation. The score obtained was compared with persistence of both villous atrophy and endomysial antibodies (EMA). The rate of lower scores was higher among the patients with persistence of either villous atrophy (Fisher's exact, P < 0.001; test for trend, P < 0.001) or positive EMA (Fisher's exact, P = 0.001; test for trend, P = 0.018). Given that the coeliac patients have been well instructed on what a GFD means and on how to follow it, our questionnaire is a reliable and simple method to verify compliance to a GFD. PMID- 22321200 TI - Biomechanical and magnetic resonance imaging evaluation of a single- and double row rotator cuff repair in an in vivo sheep model. AB - PURPOSE: To investigate the biomechanical and magnetic resonance imaging (MRI) derived morphologic changes between single- and double-row rotator cuff repair at different time points after fixation. METHODS: Eighteen mature female sheep were randomly assigned to either a single-row treatment group using arthroscopic Mason Allen stitches or a double-row treatment group using a combination of arthroscopic Mason-Allen and mattress stitches. Each group was analyzed at 1 of 3 survival points (6 weeks, 12 weeks, and 26 weeks). We evaluated the integrity of the cuff repair using MRI and biomechanical properties using a mechanical testing machine. RESULTS: The mean load to failure was significantly higher in the double row group compared with the single-row group at 6 and 12 weeks (P = .018 and P = .002, respectively). At 26 weeks, the differences were not statistically significant (P = .080). However, the double-row group achieved a mean load to failure similar to that of a healthy infraspinatus tendon, whereas the single-row group reached only 70% of the load of a healthy infraspinatus tendon. No significant morphologic differences were observed based on the MRI results. CONCLUSIONS: This study confirms that in an acute repair model, double-row repair may enhance the speed of mechanical recovery of the tendon-bone complex when compared with single-row repair in the early postoperative period. CLINICAL RELEVANCE: Double-row rotator cuff repair enables higher mechanical strength that is especially sustained during the early recovery period and may therefore improve clinical outcome. PMID- 22321201 TI - Results of carbon ion radiotherapy for head and neck cancer. AB - PURPOSE: To evaluate the efficacy of carbon ion radiotherapy for head-and-neck cancer in a phase II clinical trial. MATERIALS AND METHODS: Between April 1997 and February 2006, 236 patients with locally advanced, histologically proven, and new or recurrent cancer of the head and neck were treated with carbon ions. The treatment dose was 64.0 GyE/16 fractions/4 weeks (or 57.6 GyE/16 fractions/4 weeks when the wide-range skin was included in the target volume). RESULTS: There were grade 3 acute skin reactions in 6% and grade 3 acute mucosal reactions in 10% with no acute reactions worse than grade 3, and grade 2 late skin reactions in 3% and grade 2 late mucosal reactions in 2% with no late reactions worse than grade 2. The 5-year local control rate, by histological type, was 75% for the 85 patients with malignant melanoma, 73% for the 69 with adenoid cystic carcinoma, 73% for the 27 with adenocarcinoma, 61% for the 13 with papillary adenocarcinoma, 61% for the 12 with squamous cell carcinoma and 24% for the 14 with sarcomas. The 5-year over-all survival rate was 68% for adenoid cystic carcinoma, 56% for adenocarcinoma and 35% for malignant melanoma. CONCLUSIONS: Carbon ion radiotherapy for head and neck cancer showed the therapeutic effectiveness for malignant melanoma and adenoid cystic carcinoma without severe morbidity of the normal tissues. PMID- 22321202 TI - Long-term symptoms after radiotherapy of supraclavicular lymph nodes in breast cancer patients. AB - BACKGROUND AND PURPOSE: Irradiation of the supraclavicular lymph nodes has historically increased the risk of brachial plexopathy. We report long-term symptoms after modern radiotherapy (based on 3D dose planning) in breast cancer patients with or without irradiation of the supraclavicular lymph nodes. MATERIAL AND METHODS: We collected information from 814 women consecutively treated with adjuvant radiotherapy for breast cancer. The women had breast surgery with axillary dissection (AD) or sentinel node biopsy (SNB). The breast area was treated to 50 Gy in 2.0 Gy fractions. Women with >three lymph node metastases had regional radiotherapy (RRT) to the supraclavicular lymph nodes. Three to eight years after radiotherapy, they received a questionnaire asking about paraesthesia, oedema, pain, and strength in the upper limb. RESULTS: Paraesthesia was reported by 38/192 (20%) after AD with RRT compared to 68/505 (13%) after AD without RRT (relative risk [RR] 1.47; 95% confidence interval [CI] 1.02-2.11) and by 9/112 (8%) after SNB without RRT (RR 2.46; 95% CI 1.24-4.90). Corresponding risks adjusted for oedema (RR 1.28; 95% CI 0.93-1.76) and (RR 1.75; 95% CI 0.90 3.39). In women <= 49years with AD and RRT, 27% reported paraesthesia. No significant pain or decreased strength was reported after RRT. CONCLUSION: Radiotherapy to the supraclavicular lymph nodes after axillary dissection increases the occurrence of paraesthesia, mainly among younger women. When adjusted for oedema the contribution from radiotherapy is no longer formally statistically significant indicating that there is also an indirect effect mediated by the oedema. PMID- 22321203 TI - The Five-Factor Model of personality disorder and DSM-5. AB - The Five-Factor Model of personality disorders (FFMPD; Widiger & Mullins-Sweatt, ) developed from the recognition that the popular Five-Factor Model (FFM) of personality could be used to describe and understand the official personality disorder (PD) constructs from the American Psychiatric Association's (APA) diagnostic manuals (e.g., DSM-IV-TR, APA, ). This article provides an overview of the FFM, highlighting its validity and utility in characterizing PDs as well as its ability to provide a comprehensive account of personality pathology in general. In 2013, DSM-5 is scheduled to appear, and the "hybrid" PD proposal will emphasize a 25-personality trait model. I present the current version of this new model, compare it to the FFMPD, and discuss issues related to the implementation of the FFMPD. PMID- 22321204 TI - Examination of midlife women's attitudes toward menopause in Turkey. AB - This study used a cross-sectional descriptive design to examine the attitudes of 154 Turkish women aged >= 40 years towards menopause. A questionnaire and the Menopause Attitudes scale were used. The mean score of the attitudes was determined as 34.70 +/- 8.56. Most women in the study had negative attitudes towards menopause. The majority of women with positive attitudes were older, well educated and had used hormone replacement therapy (P < 0.05). Using multiple linear regression analysis, age and education level were found to be statistically significant (P < 0.001). A statistically significant difference was found between the women in the premenopausal and menopausal years in terms of sexuality after menopause (P < 0.05). This study suggests that Turkish women 40 years and older have negative attitudes towards menopause and their primary concern in the premenopausal period is sexuality after menopause. Counseling of women on menopause-related issues in gynecology clinics is recommended. PMID- 22321205 TI - Mesothelioma of tunica vaginalis testis and asbestos exposure. AB - Study Type - Therapy (case series). Level of Evidence 4. What's known on the subject? and What does the study add? Mesothelioma of the tunica vaginalis testis is a rare tumour. From 2000 to 2010, 13 mesothelioma of the tunica vaginalis testis cases were reported in the most populated and industrialized region in Italy. Asbestos exposure was documented in two-thirds of these cases. OBJECTIVE: * To describe cases of mesothelioma of the tunica vaginalis testis (MTVT) recorded in the Lombardy Mesothelioma Registry between 2000 and 2010. METHODS: * The Lombardy Mesothelioma Registry, established in 2000, collects data regarding all incident cases of mesothelioma of the pleura, peritoneum, pericardium and tunica vaginalis testis that have been diagnosed in the population of the Lombardy region. * These data include a detailed clinical report and a complete occupational history for each MTVT patient, with the latter including details of the industrial sector involved, the patient's job, and the specific tasks performed. To address the potential for asbestos exposure outside the work environment, the residential history, lifestyle habits and hobbies of the patient, as well as job information for all subjects living with the patient, are also collected. * Records were reviewed and discussed by a panel of experts. RESULTS: * Thirteen cases of MTVT were reported between 2000 and 2010. * The age standardized incidence rate of MTVT for the Lombardy region of Italy is 0.2 cases per million individuals/year. * Asbestos exposure was documented in 8 of the 12 (67%) interviewed cases. CONCLUSIONS: * Asbestos exposure was associated with a higher proportion of MTVT cases than previously reported in the literature. These results confirm the aetiological role for asbestos in the pathogenesis of MTVT. * The results of this study also highlight the importance of obtaining detailed occupational histories and lifestyle habits from patients, particularly by trained interviewers. PMID- 22321206 TI - Implications of the recent reductions in natural gas prices for emissions of CO2 from the US power sector. AB - CO(2) emissions from the US power sector decreased by 8.76% in 2009 relative to 2008 contributing to a decrease over this period of 6.59% in overall US emissions of greenhouse gases. An econometric model, tuned to data reported for regional generation of US electricity, is used to diagnose factors responsible for the 2009 decrease. More than half of the reduction is attributed to a shift from generation of power using coal to gas driven by a recent decrease in gas prices in response to the increase in production from shale. An important result of the model is that, when the cost differential for generation using gas rather than coal falls below 2-3 cents/kWh, less efficient coal fired plants are displaced by more efficient natural gas combined cycle (NGCC) generation alternatives. Costs for generation using NGCC decreased by close to 4 cents/kWh in 2009 relative to 2008 ensuring that generation of electricity using gas was competitive with coal in 2009 in contrast to the situation in 2008 when gas prices were much higher. A modest price on carbon could contribute to additional switching from coal to gas with further savings in CO(2) emissions. PMID- 22321207 TI - What is the impact on sexual function of laparoscopic treatment and subsequent combined oral contraceptive therapy in women with deep infiltrating endometriosis? AB - INTRODUCTION: Deep infiltrating endometriosis (DIE) is a form of endometriosis in which the lesion penetrates for more than 5 mm under the peritoneal surface. It is a chronic disease which can impair women's sexual function. There is a growing body of evidence supporting combined surgical/medical treatment in the management of DIE. AIMS: The aims of this article are to evaluate the impact of the laparoscopic full excision of endometriosis and postoperative combined oral contraceptives (COC) administration on sexual function in patients with DIE and to compare sexual function outcomes of women submitted to intestinal resection and nodule excision. METHODS: It is a prospective cohort study in a tertiary care university hospital on 106 sexually active women, with histologically confirmed DIE, managed by laparoscopy and subsequent COC therapy for 6 months. Patients filled preoperatively and 6-month postoperatively a quality of sexual life questionnaire, the Sexual Health Outcomes in Women Questionnaire (SHOW-Q) and they ranked their symptom intensity using a 10-point visual analogue scale (VAS). MAIN OUTCOME MEASURES: Sexual function was measured through the SHOW-Q scores and pain symptoms through VAS scores. Intraoperative details, type of intervention and perioperative complications were noted. RESULTS: Six months after surgery and postoperative COC treatment, a significant improvement was observed in the SHOW-Q domains of pelvic problem interference, sexual satisfaction and desire (P<0.05). Laparoscopic management of DIE did not change significantly the orgasm area of the sexual functioning (P=0.7). No significant difference was found in SHOW-Q scores between patients submitted to intestinal resection and patients submitted to intestinal nodule excision (P>0.05). CONCLUSIONS: Sexual desire, satisfaction with sex and pelvic problem interference with intercourse are significantly improved after 6 months from laparoscopic excision of DIE combined with postoperative COC therapy. No difference in sexual outcomes was detected between patients submitted to intestinal resection and nodule excision. PMID- 22321208 TI - Continuous venovenous hemofiltration and hemoperfusion in successful treatment of a patient with crush syndrome and acute pancreatitis. AB - In this article, we report a patient with crush syndrome (CS) who developed acute renal failure (ARF) and acute pancreatitis. Continuous venovenous hemofiltration (CVVH) and intermittent hemoperfusion (HP) were successfully performed in this patient and satisfactory effects were achieved. The treatment of this patient suggested that early intervention with continuous renal replacement therapy (CRRT) may be useful and a multiple-mode treatment may be a better choice. PMID- 22321209 TI - Complications of apheresis. AB - In general, therapeutic apheresis is a relatively safe procedure with the most commonly seen complications caused by citrate-induced hypocalcemia and urticarial reactions to the protein-containing replacement fluid. Depletion coagulopathy and immunoglobulin depletion must be anticipated when albumin is used as the replacement fluid and becomes more profound as the number of treatment increases. The most serious complications are seen when there is an anaphylactoid reaction to the multiple units of fresh frozen plasma required when used as the replacement fluid. The overall incidence of death is 0.05%, but many of these deaths were in patients with severe preexisting conditions in which the apheresis procedure, itself, may not have been the precipitating cause. As with all extracorporeal treatments requiring large bore vascular access, catheter-related trauma, clotting, infection, and bleeding may also occur. PMID- 22321210 TI - Characteristics of thawed autologous umbilical cord blood. AB - BACKGROUND: Autologous umbilical cord blood (AutoUCB) has historically been cryopreserved for potential use in hematopoietic transplantation. Increasingly, private AutoUCB banking is performed for therapies unavailable today. A Phase I trial using AutoUCB treatment for early pediatric Type 1 diabetes afforded us an opportunity to analyze characteristics of AutoUCBs. STUDY DESIGN AND METHODS: Twenty AutoUCBs from AABB-accredited private cord blood banks (CBBs) were evaluated for collection, processing, cryopreservation, and thaw characteristics. Using a standardized thaw-wash method, AutoUCBs were assessed for viable total nucleated cells (vTNCs), viable CD34+ (vCD34+), and colony-forming unit granulocyte-macrophage counts. Postthaw %vTNC recoveries were compared against processing characteristics and analyzed according to processing method, cryopreservation volume, concentration, container, and length of storage. RESULTS: AutoUCB collection volumes (19.9-170 mL), cryopreserved TNC counts (7.6 * 10(7) -3.34 * 10(9)), %TNC processing recoveries (39%-100%), postthaw %vTNC recoveries (58%-100%), and %vCD34+ recoveries (26%-96%) varied widely. Regarding cell dose requirements, only 11% of evaluable AutoUCBs achieved the minimum TNC count of at least 9.0 * 10(8) to meet the National Cord Blood Inventory banking threshold, and only 50% met the minimum of 5.0 * 10(8) TNC count for Food and Drug Administration cord blood licensure eligibility. %vTNC recoveries correlated with %vCD34+ recoveries (R = 0.7; p = 0.03). Length of storage, cryopreservation volume, concentration, and container type did not affect postthaw %vTNC recoveries. CBB processing method, however, was associated with %vTNC postprocessing recoveries, with unmanipulated and plasma-depleted AutoUCBs having the highest postthaw %vTNC recovery, followed by RBC-depleted and density gradient-separated AutoUCBs. CONCLUSION: The high variability and low counts found in AutoUCB banking suggest that further standardization of characterization, collection, and processing procedures is needed. PMID- 22321211 TI - Biochemical mapping of a ligand-binding domain within Arabidopsis BAM1 reveals diversified ligand recognition mechanisms of plant LRR-RKs. AB - Leucine-rich repeat receptor kinases (LRR-RKs) are the largest sub-family of transmembrane receptor kinases in plants. In several LRR-RKs, a loop-out region called an 'island domain', which intercepts the extracellular tandem LRRs at a position near the transmembrane domain, constitutes the ligand-binding pocket, but the absence of the island domain in numerous LRR-RKs raises questions about which domain recognizes the ligand in non-island domain LRR-RKs. Here, we used photoaffinity labeling followed by chemical and enzymatic digestion to show that BAM1, a CLV1/BAM-family LRR-RK whose extracellular domain comprises 22 consecutive LRRs, directly interacts with the small peptide ligand CLE9 at the LRR6-LRR8 region that is relatively distal from the transmembrane domain. Multiple sequence alignment and homology modeling revealed that the inner concave side of LRR6-LRR8 of CLV1/BAM-family LRR-RKs deviates slightly from the LRR consensus. In support of our findings, the clv1-4 mutant carries a missense mutation at the inner concave side of LRR6 of CLV1, and introduction of the corresponding mutation in BAM1 resulted in complete loss of ligand binding activity. Our results indicate that the ligand recognition mechanisms of plant LRR-RKs are more complex and diverse than anticipated. PMID- 22321212 TI - Reduced contact resistance in inkjet printed high-performance amorphous indium gallium zinc oxide transistors. AB - Solution processing of amorphous metal oxide materials to fabricate thin-film transistors (TFTs) has received great recent interest. We demonstrate here an optimized "ink" and printing process for inkjet patterning of amorphous indium gallium zinc oxide (a-IGZO) TFTs and investigate the effects of device structure on derived electron mobility. Bottom-gate top-contact (BGTC) TFTs are fabricated and shown to exhibit electron mobilities comparable to a-Si:H. Furthermore, a record electron mobility of 2.5 cm(2) V(-1) s(-1) is demonstrated for bottom-gate bottom-contact (BGBC) TFTs. The mechanism underlying such impressive performance is investigated using transmission line techniques, and it is shown that the semiconductor-source/drain electrode interface contact resistance is nearly an order of magnitude lower for BGBC transistors versus BGTC devices. PMID- 22321213 TI - Effect of alkyl chain length on sphingosine kinase 2 selectivity. AB - The conversion of sphingosine to sphingosine-1-phosphate is catalyzed by sphingosine kinase (SphK), which has been implicated in disease states such as cancer and fibrosis. Because SphK exists as two different isoforms, SphK1 and SphK2, understanding the physiological function of each isoenzyme is important. Of the two isoenzymes, SphK2 is significantly less understood, which is evident by the lack of selective small molecule inhibitors. Building on our initial work that focused on the structure-activity relationship study on an FTY720-derived cylohexylamine scaffold, we report that varying the alkyl chain length on the hydrophobic tail can impart selectivity toward SphK2 over SphK1. PMID- 22321214 TI - Discovery of 4-hydroxy-1,6-naphthyridine-3-carbonitrile derivatives as novel PDE10A inhibitors. AB - A series of 1,6-naphthyridine-based compounds was synthesized as potent phosphodiesterase 10A (PDE10A) inhibitors. Structure-based chemical modifications of the discovered chemotype served to further improve potency and selectivity over DHODH, laying the foundation for future optimization efforts. PMID- 22321215 TI - Anti-tumor activity of new orally bioavailable 2-amino-5-(thiophen-2-yl)benzamide series histone deacetylase inhibitors, possessing an aqueous soluble functional group as a surface recognition domain. AB - New orally bioavailable 5-(thiophen-2-yl)-substituted 2-aminobenzamide-series histone deacetylase inhibitors were synthesized. These compounds possess a morpholine or piperadine-derived moiety as an aqueous soluble functional group. Among them, 8b, having a 4-ethyl-2,3-dioxopiperazine-1-carboxamide group as a surface recognition domain, showed promising inhibitory activities against HCT116 cell growth and HDAC1/2. Notably, unlike MS-275, this compound did not induce apoptosis in the cell cycle tests. We therefore conducted antitumor tests of 8b and MS-275 against HCT116 cell xenografts in nude mice. Compound 8b reduced the volume of tumor mass to T/C: 60% and 47% at 45 and 80mg/kg over 16days, respectively. These values were comparable to the rate (T/C: 51% at 45mg/kg) for MS-275. Furthermore, 8b, at neither 45 nor 80mg/kg, induced the weight loss which was observed in the mice given MS-275 at 45mg/kg. PMID- 22321216 TI - Towards the preparation of radiolabeled 1-aryl-3-benzyl ureas: Radiosynthesis of [(11)C-carbonyl] AR-A014418 by [(11)C]CO(2) fixation. AB - The highly selective glycogen synthase kinase-3 (GSK-3) inhibitor N-(4 methoxybenzyl)-N'-(5-nitro-1,3-thiazol-2-yl)urea (AR-A014418) was radiolabeled with carbon-11 ((11)C; half-life=20.4min) at the urea moiety via [(11)C]CO(2) fixation. Reaction of [(11)C]CO(2) with 4-methoxybenzylamine in the presence of a CO(2) fixating base was followed by dehydration with POCl(3) and addition of 2 amino-5-nitrothiazole to prepare [(11)C-carbonyl] AR-A014418. This reaction resulted in an 8% uncorrected radiochemical yield, based on [(11)C]CO(2), with high specific activity (4Ci/MUmol) within 30min. An in vitro GSK-3beta enzyme activity assay revealed that AR-A014418 (K(i)=770nM) is not as potent as previously claimed. The [(11)C]CO(2) fixation methodology described herein should prove generally applicable to preparing 1-aryl-3-benzyl-[(11)C-carbonyl] ureas as radiotracers for positron emission tomography. PMID- 22321217 TI - Interlaboratory comparison of current high-performance methods for HbA2. AB - INTRODUCTION: Few data are available on the alignment of the different methods used for HbA(2) quantitation and recent external quality survey results show a consistent spread of HbA(2) values. To this aim, a comparison study among the actual best performing techniques for HbA(2) determination, comprising HPLC and CE methods, was performed. METHODS: A total of 80 blood samples collected from normal subjects and beta-thalassemia carriers were analyzed by different HPLC (Bio-Rad Variant I, Bio-Rad Variant II, Menarini HA-8160, Tosoh G7, Tosoh G8) and capillary electrophoresis (Beckman Coulter MDQ and ProteomeLab PA 800, Sebia Capillarys 2) methods. Patient's samples with clinically relevant hemoglobin variants (HbC, HbD, HbE, HbS, and delta-chain variants) were also tested by all methods. RESULTS: The mean within-run imprecision of HbA(2) measurement (expressed as CV, %) was between 0.5% and 4.4% (HPLC) and between 1.2% and 4.4% (capillary electrophoresis). The comparison study showed that the different methods were highly correlated (r between 0.974 and 0.997) although biased each other. HbA(2) determination in presence of abnormal hemoglobins was variously interfered by both HPLC and CE methods. Concerning HbF, the mean imprecision at HbF values >=1.5% was between 1.2% and 8.2% (as CVs). CONCLUSIONS: A poor alignment of routine methods for HbA(2) measurement was found. The need of a better standardization of HbA(2) measurement procedures was underlined. PMID- 22321218 TI - Abnormal circadian blood pressure regulation in liver transplanted children. AB - HT is a frequent cardiovascular risk factor in liver transplant recipients. However, there are only few studies in the literature regarding the risk of HT in liver transplanted children. The aim of this study was to assess the 24 h BP profiles of liver transplanted patients and to compare the results with healthy children. ABPM was performed on 20 liver transplanted patients and 27 healthy children aged 7.1 +/- 4.8 and 8.5 +/- 2.9 yr, respectively. HT was defined as SDS > 1.64 (i.e., >95th percentile) adjusted for gender and height. The mean duration of post-transplant follow-up was 32 +/- 19 months. Six (30%) patients were found to be hypertensive. The physiological nocturnal BP fall was attenuated significantly in the study group for diastolic BP (11.5 +/- 6.1 mmHg vs. 17.7 +/- 7.1 mmHg, p = 0.006). Specifically, the number of patients with high nighttime systolic and diastolic BP SDS (p = 0.02 and p = 0.004, respectively) as well as elevated nighttime systolic (p = 0.03) and diastolic (p = 0.003) BPLs was found to be significantly higher than those in the controls. Alteration of the "normal" circadian rhythm is very frequent in liver transplant recipients. Thus, it is recommended to perform ABPM on all liver transplanted children not to underdiagnose HT. PMID- 22321219 TI - Diabetes and the risk for colorectal cancer. AB - Diabetes mellitus has been reported to be associated with an increased risk for colorectal cancer. The review analyzes current epidemiological data on the association of diabetes and the risk for colorectal cancer. Hyperinsulinemia, hyperglycemia, and inflammation are suggested to play a key role in the pathophysiology of cancer in diabetes. Data regarding potential treatment-related risks, particularly in conjunction with the use of insulin and insulin analogues, are also presented. Furthermore, the impact of glycemic control and cardiorespiratory fitness on cancer prognosis is considered. Finally, the preventive potential of aspirin and other nonsteroidal anti-inflammatory drugs, and the recommendations concerning colonoscopy-screening are presented. PMID- 22321221 TI - [Current issues in atherosclerosis research]. PMID- 22321220 TI - Social adaptability index predicts overall mortality in patients with diabetes. AB - BACKGROUND: A quantifiable assessment of socioeconomic status and its bearing on clinical outcome in patients with diabetes is lacking. The social adaptability index (SAI) has previously been validated in the general population and in patients with chronic kidney disease, including those on dialysis and with kidney transplant. We hypothesize that SAI could be used in diabetes practice to identify a disadvantaged population at risk for inferior outcomes. METHODS: The NHANES-3 database of patients who have diabetes was analyzed. The association of the SAI (calculated as the linear combination of indicators of education status, employment, income, marital status, and substance abuse) with patient survival was evaluated using Cox model. RESULTS: The study population consisted of 1634 subjects with diabetes mellitus with mean age of 61.9+/-15.3 years; 40.9% males; 38.5% white, 27.7% African American, and 31.3% Mexican American. The highest SAI was in whites (6.9+/-2.5), followed by Mexican Americans (6.5+/-2.3), and then African Americans (6.1+/-2.6) (ANOVA, P<.001). SAI was higher in subjects living in metropolitan areas (6.8+/-2.6) compared to the rural population (6.3+/-2.4) (T test, P<.001). Also, SAI was greater in males (7.1+/-2.4) than in females (6.1+/ 2.4) (T test, P<.001). SAI had significant association with survival (hazard ratio 0.9, P<.001) in the entire study population and in most of the subgroups (divided by race, sex, and urban/rural location). Furthermore, SAI divided into tertiles (<=5, 6 to 8, >8) demonstrated a significant and "dose-dependent" association with survival. CONCLUSION: Social adaptability index is associated with mortality in the diabetic population and is useful in identifying individuals who are at risk for inferior outcomes. PMID- 22321222 TI - [Relationship between high triglyceride and risk of coronary heart disease]. PMID- 22321223 TI - [Clinical thinking on the intensive lipid-lowering therapy]. PMID- 22321224 TI - [Expert consensus on management of hypertriglyceridemia]. PMID- 22321225 TI - [Roles of monocyte chemoattractant protein-1, RANTES and Fractalkine on promoting vulnerability of atherosclerotic plaques]. AB - OBJECTIVE: To elucidate the roles of monocyte chemotactic factors (MCP-1, RANTES and Fractalkine) on the vulnerability of atherosclerotic plaques in patients with stable (SAP) and unstable angina pectoris (UAP). METHODS: Patients with SAP (n = 50) and UAP (n = 50) underwent coronary angiography (CAG) and intravenous ultrasound (IVUS) were included in the study. Monocyte chemotaxis was assayed by the transwell chamber. Concentrations of hs-CRP, MCP-1, RANTES and Fractalkine were measured by Enzyme-linked-immunosorbent assay (ELISA). mRNA expression of MCP-1, RANTES and Fractalkine in the monocytes was detected by RT-PCR. RESULTS: IVUS evidenced soft lipid plaques in 48% UAP patients and in 16% SAP patients (P < 0.05). SAP patients had mainly fibrous and mixed plaques. Plaque burden and vascular remodeling index were significantly higher in UAP patients than in SAP patients (P < 0.01). The averaged number of migrated monocytes in the UAP patients were higher than that in patients with SAP (P < 0.01). Concentration of hs-CRP, MCP-1, RANTES and Fractalkine were significantly higher in UAP patients than those of SAP patients (P < 0.05 or P < 0.01). mRNA expression of MCP-1, RANTES and Fractalkine in patients with UAP was significantly higher than those of SAP patients (P < 0.05). CONCLUSION: Upregulated monocyte chemotactic factors (MCP-1, RANTES and Fractalkine) might promote coronary plaque vulnerability in UAP patients. PMID- 22321226 TI - [Clinicopathologic analysis of vulnerable plaque in autopsy with acute coronary syndrome]. AB - OBJECTIVE: To observe pathohistological features of vulnerable plaques in coronary arteries. METHODS: Autopsy coronary samples from 67 patients died of acute coronary syndrome (ACS) and 60 patients of non-cardiac death from 1992 to 2006 in Beijing Hospital were examined. Morphological features of vulnerable plaques of ACS cases were evaluated in terms of thrombus, ratio of lipid core, the minimal thickness of fibrous cap and the density of inflammatory infiltration. RESULTS: (1) There are 305 plaques in ACS group and the incidence of big lipid core is 153 (50.16%), thin fibrous cap is 187(61.31%), inflammatory infiltration is 263 (86.23%), neovasculature conformation is 217 (71.15%), severe stenosis is 26 (8.52%), calcification is 238 (78.03%), superficial calcified nodule is 26 (8.52%), fissured plaque is 12 (3.93%), endothelial denudation is 3 (0.98%) and intraplaque hemorrhage is 54 (17.70%), which are significantly higher than control samples except endothelial denudation (P < 0.01). (2) The incidence of vulnerable plaques in ACS group is significantly higher than in the control group (89.51% vs. 21.98%, P < 0.01). There are 4.07 sections of vulnerable plaques with high density of inflammatory infiltration out of 4.55 sections reviewed in ACS patients, while there are 0.85 sections of vulnerable plaques with mild inflammatory infiltration out of 3.87 sections reviewed in the control cases. CONCLUSIONS: Formation of vulnerable plaque was an important pathological factor for the development of ACS. The major morphological characteristics of vulnerable plaque are big lipid core, thin fibrous cap, inflammatory infiltration, neovascularization, severe stenosis, plaque rupture, and endothelial denudation suggesting inflammation performed an important role in the formation of vulnerable plaque. PMID- 22321227 TI - [Association between high sensitivity C-reactive protein and contrast induced acute kidney injury in patients with acute coronary syndrome undergoing percutaneous coronary intervention: impact of atorvastatin]. AB - OBJECTIVE: To observe the association between preprocedural high sensitivity C reactive protein (hs-CRP) level and incidence of contrast induced acute kidney injury (CI-AKI) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) and the impact of atorvastatin pretreatment on CI AKI. METHODS: According to the level of preprocedural hs-CRP, 270 ACS patients were divided into three groups: high hs-CRP group (hs-CRP >= 3 mg/L, n = 176), moderate hs-CRP group (hs-CRP 1-3 mg/L, n = 60) and normal hs-CRP group (hs-CRP < 1 mg/L, n = 34). According to the dosage of preprocedural atorvastatin, the high hs-CRP group was further divided into 10 mg group (n = 49), 20 mg group (n = 66) and 40 mg group (n = 61). Serum creatinine (Scr), blood urea nitrogen (BUN), cystatin C (Cys C), hs-CRP were measured at before and 24 hours, 48 hours after PCI. CCr and GFR were calculated according to Scr and Cys C. Risk factors for CI AKI were determined by multivariate logistic regression analysis. RESULTS: (1) Cys C was significantly increased and GFR after PCI significantly reduced in high and moderate hs-CRP groups compared with normal hs-CRP group (P < 0.05). (2) Incidence of CI-AKI was 43.18%, 38.33%, 20.59% in high, moderate and normal hs CRP groups, respectively (P < 0.05). (3) In high hs-CRP group, postprocedural GFR was significantly higher while postprocedural Cys C and hs-CRP were significantly lower in 40 mg statin subgroup than 10 mg and 20 mg statin subgroups (P < 0.05), similar trends were documented when comparing 20 mg statin subgroup with 10 mg statin subgroup (P < 0.05). (4) Multivariate logistic regression analysis showed that pretreatment with high dose atorvastatin was a protective factor for post CI AKI (20 mg atorvastatin: OR = 0.15, 95%CI 0.06 - 0.33, P = 0.001; 40 mg atorvastatin: OR = 0.10, 95%CI 0.04 - 0.23, P = 0.001), while high levels of preprocedural hs-CRP (OR = 2.06, 95%CI 1.01 - 4.23, P = 0.048), diabetes mellitus (OR = 10.71, 95%CI 5.29 - 21.70, P = 0.001), advanced age (OR = 2.64, 95%CI 1.05 6.63, P = 0.038) and renal failure (OR = 5.14, 95%CI 1.13 - 23.39, P = 0.034) were independent risk factors of CI-AKI. CONCLUSION: High hs-CRP level is linked with the development of CI-AKI in ACS patients undergoing PCI and pretreatment with 40 mg atorvastatin is associated with lower incidence CI-AKI, possibly by reducing the postprocedural inflammation responses. PMID- 22321228 TI - [Clinical manifestations of 43 patients with acute myocardial infarction complicated by free wall rupture]. AB - OBJECTIVE: To analyze the clinical characteristics of patients with acute myocardial infarction (AMI) complicated by free wall rupture (FWR) and to define the independent risk factors for FWR. METHODS: Clinical and angiographic data of 6192 AMI patients admitted to our department between January 1995 and January 2010 were retrospectively reviewed, FWR was confirmed in 43 patients by post mortem examination. Multivariate logistic regression analysis was performed to identify risk factors for FWR. RESULTS: Rupture occurred at a median of 3.58 days after symptom onset. Risk factors associated with FWR were older age, female gender, delayed hospital admission, hypertension at admission and increased serum creatine level. Although patients with FWR had more single-vessel disease, their in-hospital mortality was very high (97.7%). Undue physical efforts were documented in 41.9% patients with FWR. CONCLUSION: Old age, female gender and prolonged time from the onset of symptoms to hospital, hypertension and high level of serum creatine at admission are independent factors of FWR. PMID- 22321229 TI - [Onset timing of acute ST segment elevation myocardial infarction in middle-aged and old patients]. AB - OBJECTIVE: To compare the differences on onset timing of acute ST segment elevation myocardial infarction (STEMI) in young and aged patients. METHODS: The exact onset time of symptoms was obtained from 1024 consecutive patients with STEMI admitted to our hospital between January 2000 and May 2010. Patients were classified as the middle-aged group [< 65 years old, mean (52.2 +/- 8.0) years, n = 536] and old group [>= 65 years old, (72.2 +/- 5.5) years, n = 488], the difference of the onset months, weeks, weekdays and hours between two groups was compared. RESULTS: The high onset timing of STEMI in middle-aged group was October and February, Friday, Saturday and Wednesday, at 10 A.m. and 10 P.m. The high onset timing of STEMI in old group was October, January and March, Friday, Sunday and Monday, at 6 A.m. and 2 A.m. The incidences of STEMI in the old group were significant higher than in the middle-aged group in March (11.89%), on Sunday (15.97%) and Monday (17.42%), at 6 A.m. (6.35%) and 2 A.m. (5.74%) (all P < 0.05) while the onset rate was significant higher in February (9.89%), On Saturday (16.98%), At 8 P.m. (4.86%) and 10 P.m. (5.78%) in the middle-aged group than old group (all P < 0.05). CONCLUSION: The onset timing of STEMI in old patients was significant different from the middle-aged patients suggesting the onset timing of STEMI changes with aging. PMID- 22321230 TI - [Pressure wave reflections and central blood pressure in treated hypertensive subjects]. AB - OBJECTIVE: To investigate the differences in pressure wave reflections and central blood pressure between brachial BP classification and the effect of antihypertensive drugs. METHOD: In 1371 chronically treated hypertensive subjects aged 33 - 87 years [679 males and 692 females, mean age (47.2 +/- 11.5) years], radial arterial augmentation index (rAI) and central systolic blood pressure were measured using an automated tonometric method. RESULTS: rAI gradually increased from the subgroup with the lower blood pressure to the higher blood pressure (P < 0.01), for each given brachial value, central systolic blood pressure was lower than the corresponding brachial pressure (P < 0.01). In multivariable linear regression models analysis revealed that the application of angiotensin converting enzyme inhibitor (beta = -0.09, P < 0.05), AT1 receptor blockade (beta = -0.07, P = 0.01), calcium channel blocker (beta = -0.12, P < 0.01) and diuretic (beta = 0.14, P = 0.04) were independent determinants of rAI. Central SBP significantly correlated to the application of ACEI (beta = -0.07, P = 0.02), ARB (beta = -0.08, P = 0.01) and CCB (beta = -0.15, P < 0.05). CONCLUSIONS: In chronically treated hypertensive individuals, tight blood pressure control would be effective in reducing the reflection wave and central BP. Antihypertensive treatment strategies with more beneficial effects on arterial properties are needed. PMID- 22321231 TI - [Impact of smoking and smoking cessation on long-term outcome of patients after coronary artery bypass grafting]. AB - OBJECTIVE: To determine the impact of smoking behaviors on long-term outcomes of coronary artery bypass grafting (CABG). METHODS: We conducted this survey in 2541 consecutive patients who underwent CABG in Fu Wai hospital from January 1, 2004 to December 30, 2005. The preoperative and postoperative smoking habits were obtained. The patients were divided into never smokers and ever smokers. The ever smokers were further divided into the current smokers who smoked before and after CABG and former smokers who stopped smoking before CABG, quitters who stopped smoking after CABG. Death, major adverse cardiovascular or cerebrovascular events and angina pectoris were observed. The relative risk of adverse events in different patients were analyzed by univariate and multivariate Cox analysis. RESULTS: The patients were followed up for 4.27 to 6.41 years (average 5.09 years). After CABG, the percentage of persistent smoking patients was 22.1%. After adjusting baseline characteristics, relative risk for tumor related death (RR: 2.38, 95%CI: 1.06 - 5.36), major adverse cardiovascular or cerebrovascular events (RR: 1.26, 95%CI: 1.01 - 1.57) and angina pectoris (RR: 1.29, 95%CI: 1.04 1.59) were significantly higher in ever smokers than in never smokers. Similarly, relative risk of death from all causes (RR: 2.60, 95%CI: 1.53 - 4.46), cardiac death (RR: 2.51, 95%CI: 1.32 - 4.78), tumor cause death (RR: 5.12, 95%CI: 2.08 - 12.59), major adverse cardiovascular or cerebrovascular events (RR: 1.83, 95%CI: 1.42 - 2.34) and angina pectoris (RR: 1.69, 95%CI: 1.33 - 2.16) were also significantly higher in current smokers than in never smokers. Outcome was similar between patients who stopped smoking and never smokers (all P > 0.05). CONCLUSIONS: Smoking prevalence is still high in patients after CABG in China. Persistent smoking is associated with higher rates of mortality and morbidity after CABG while smoking cessation is associated with reduction of morbidity and mortality in patients after CABG. PMID- 22321232 TI - [Value of cardiac CT examination in middle-aged and elderly patients with atrial septal defect before planned transcatheter closure]. AB - OBJECTIVE: To investigate the value of the cardiac CT examination for decision making in middle-aged and elderly patients before planned transcatheter atrial septal defect (ASD) closure. METHODS: Cardiac CT was performed in 63 adult patients [18 males, aged from 50 to 77 years, mean age (56.87 +/- 5.79) years] with ASD before planned transcatheter ASD closure. Coronary CT angiography was made for detection of associated cardiovascular diseases, followed by 3D reconstruction of ASD for determination of the defect size in the GE-workstation, results were compared between transthoracic echocardiography measurement, CT measurement, and atrial septal defect occluder waist diameter. RESULTS: Cardiac CT identified additional cardiovascular diseases in 14 patients and decision making was changed based on cardiac CT results. Coronary artery stenosis was detected in 8 patients by cardiac CT, and proved by coronary angiography, and all of them were given comprehensive management: percutaneous coronary intervention and transcatheter ASD closure were successively performed in 2 cases, and 1 case was referred to surgery for both coronary artery bypass graft and surgical ASD repair, and 5 patients were given pharmacological management for coronary artery disease besides transcatheter ASD closure. Cardiac CT identified large ASD with insufficient rim tissue in 2 cases and transcatheter closures were abandoned. Cardiac CT screened out 1 case from those with insufficient posterior inferior rim by transthoracic echocardiography, and transcatheter ASD closure was successfully performed. Cardiac CT ruled out ASD in 1 patient. In addition, cardiac CT detected 1 partial abnormal pulmonary vein connection and 1 ductus arteriosus in this cohort. A correlation on ASD measurements was found between CT size and TTE size (r = 0.80, P < 0.01; Y = 0.84X + 8.85, R(2) = 0.63, P < 0.05), and between ASO size and CT size (r = 0.92, P < 0.01;Y = 0.93X + 4.78, R(2) = 0.84, P < 0.05). CONCLUSION: In middle-aged and elderly patients with ASD for possible transcatheter closure, cardiac CT is valuable on determine ASD size and morphology and could provide incremental information for optimizing clinical management for ASD patients. PMID- 22321233 TI - [Clinic diagnosis and treatment of patients with Cantrell syndrome]. AB - OBJECTIVE: To analyze the diagnostic feature, treatment and prognosis of patients with Cantrell syndrome. METHODS: Clinical manifestation, diagnosis, operation and follow-up data of 5 patients with Cantrell syndrome were summarized in this retrospective analysis. RESULTS: The age of the 5 patients was 7 days-76 years, definite diagnosis was made in 3 cases and 2 cases presented feature of incomplete Cantrell syndrome. Three patients with full Cantrell syndrome were correctly diagnosed before operation and confirmed by operation. One patient with incomplete Cantrell syndrome (two-vessel stenosis) received bypass surgery. Another asymptomatic patient with incomplete Cantrell syndrome (apical diverticulum of the left ventricle) does not need operation and is under observation. During follow-up, 1 patient died at 60 months after operation and the remaining 4 patients are alive and well. CONCLUSIONS: With the development of modern imaging technology, it becomes easy to make correct diagnose Cantrell syndrome before operation. Prognosis is fine post timely operation and related intervention. PMID- 22321234 TI - [Dural modulation effects of mesenchymal stem cells implantation on myocardial collagen remodeling in a rat model of myocardial infarction]. AB - OBJECTIVE: To investigate the modulation effects of mesenchymal stem cells (MSCs) implantation on the collagen remodeling in myocardial infarction. METHODS: Acute myocardial infarction (AMI) was induced in SD rats by left anterior descending coronary artery ligation, and the animals were assigned randomly into the Sham group, MI + PBS group and MI + MSCs group. Echocardiography and hemodynamic examinations were performed to evaluate the cardiac function. HE staining and Masson trichrome staining were used to evaluate the myocardial infarction size. Infarcted area and infarcted expansion index were calculated. The expression of collagens in infarcted hearts was evaluated by immunohistochemistry, RT-PCR and Western blot. RESULTS: (1) Infarct area was significantly reduced post MSCs transplantation [MI + MSCs vs. MI + PBS: (38.27 +/- 2.70)% vs. (46.20 +/- 3.17)%, P < 0.001]. (2) Cardiac function was significantly improved post MSCs transplantation [MI + MSCs vs. MI + PBS: FS(%): 29.98 +/- 4.50 vs. 23.43 +/- 3.34, P = 0.005; LVSP (mm Hg, 1 mm Hg = 0.133 kPa): 113.63 +/- 10.81 vs. 99.25 +/ 16.76, P < 0.05; LVEDP (mm Hg): 12.10 +/- 4.28 vs. 20.08 +/- 4.26, P < 0.05; +dp/dtmax (mm Hg/s): 4616.63 +/- 363.34 vs. 3912.75 +/- 248.79, P < 0.05; dp/dtmax (mm Hg/s): 4254.63 +/- 324.34 vs. 3530.88 +/- 309.71, P < 0.05]. (3) Collagen synthesis was enhanced in infarcted area and decreased in non-infarcted area post MSCs transplantation (P < 0.05). CONCLUSIONS: MSCs transplantation could enhance the collagen synthesis in infarcted area while decrease the deposition of collagen in non-infarcted area in this MI model. This may be one of the mechanisms by which ventricular remodeling is attenuated post MSCs transplantation. PMID- 22321235 TI - [Ryanodine downregulates the expression of p-eNOS (Thr495) and improves the functions of rapamycin treated endothelial outgrowth cells]. AB - OBJECTIVE: To observe the effects of ryanodine on rapamycin treated endothelial outgrowth cells (EOCs). METHODS: The mononuclear cells were harvested from umbilical cord blood by Ficoll density gradient centrifugation, then induced into EOCs and expanded in vitro. The endothelial characteristics of EOCs were identified by immunostaining and fluorescent staining. The EOCs were pretreated with or without ryanodine (10 umol/L) for 1 h, and then treated with or without rapamycin (10 nmol/L) for 24 h. Proliferation was evaluated by CCK8 and migration was measured by Transwell. The protein expression of EOCs was evaluated by immunobloting technique with total eNOS antibody and phospho-eNOS (Thr495) antibody. RESULTS: Compared with control group, the proliferation and migration capacities of EOCs were significantly reduced while the phosphorylation of eNOS (Thr495) protein was significantly upregulated in rapamycin group (P < 0.05), expression of total eNOS was not affected by rapamycin (P > 0.05). Compared with rapamycin group, the proliferation and migration capacities of EOCs were significantly increased and the phosphorylation of eNOS (Thr495) protein was significantly downregulated in ryanodine + rapamycin group (P < 0.05). The proliferation and migration capacities, the phosphorylation of eNOS (Thr495) protein and the expression of total eNOS were not affected by ryanodine alone (P > 0.05). CONCLUSIONS: Rapamycin reduced proliferation and migration capacities while upregulated the phosphorylation of eNOS (Thr495) protein of EOCs and these effects could be partly reversed by cotreatment with ryanodine. PMID- 22321236 TI - [Prenatal exposure to lipopolysaccharide results in vascular renin-angiotensin system dysfunction in offspring rats]. AB - OBJECTIVE: To explore the impact of prenatal exposure to lipopolysaccharide on renin-angiotensin system of offspring rats. METHODS: Six pregnant SD rats were randomly divided into 2 groups. The rats in the lipopolysaccharide (LPS) group were treated with LPS 0.79 mg/kg (i.p.) on the 8th, 10th and 12th day of gestation, and rats in the control group were treated with saline at the same time points. The blood pressure of offspring rats was measured by the tail cuff method. Protein expression of Angiotensin II (AngII) in thoracic aorta vessel was determined by immunohistochemistry. Protein expressions of AngII type 1 and type 2 receptor in thoracic aorta vessel were detected by Western blot. RESULTS: Blood pressure of 12-week-old offspring rats of LPS group was significantly higher than that of 12-week-old offspring rats of control group (P < 0.01). The protein expression of AngII and AngII type 1 receptor in thoracic aorta vessel were significantly higher while protein expression of AngII type 2 receptor was lower in 15-week-old offspring rats of LPS group than in control group, resulting in a significant increase in the ratio of AngII type 1 receptor/AngII type 2 receptor in the aorta at 15-week-old of offspring rats than in 15-week-old offspring rats of control group (P < 0.01). CONCLUSION: Prenatal lipopolysaccharide exposure results vascular renin-angiotensin system dysfunction, which may play an important role on the pathogenesis of hypertension development in offspring rats. PMID- 22321237 TI - [Prevalence of abnormal ankle brachial index in Xinjiang adult population]. AB - OBJECTIVE: The aim of this study was to evaluate the prevalence of abnormal ankle brachial index(ABI) in Xinjiang adult population. METHOD: Random samples maternal age 35 and over were used to analyze the prevalence and distributing feature of self-reported abnormal ABI among different nationality in 7 municipalities and locality and 26 community and autonomous county in Xinjiang. RESULTS: A total of 14 618 adults were surveyed. The prevalence of abnormal ABI was 1.26%. The prevalence of abnormal ABI was 3.56%, 7.05% and 5.79% in Han, Uygur and Hazakh population, respectively. Incidence of abnormal ABI was significantly higher in females than in males (6.65% vs 3.74%, chi(2) = 58.79, P = 0.00). Gender, nationality, systolic blood pressure, body mass index were independent predictors for abnormal ABI. CONCLUSIONS: The results of this study showed higher prevalence rate of abnormal ABI, especially in females, in Xinjiang. Nationality and gender are predictors for abnormal ABI. PMID- 22321238 TI - [Epidemiological characteristics and control status of hypertension in rural area of the Three Gorges]. AB - OBJECTIVE: To evaluate the epidemiological features and control status of hypertension in rural area of The Three Gorges. METHODS: A cross-sectional survey was carried out in rural area of Yiling District, Yichang City, which was located north-west bank of Xiling Gorges in 2007. A standard structure questionnaire was used to collect data on the hypertension history and treatment, social-economic status and life-styles, and so on. Blood pressure was measured by trained observers using standardized mercury sphygmomanometer. Hypertension was defined as systolic blood pressure >= 140 mm Hg (1 mm Hg = 0.133 kPa) and/or diastolic >= 90 mm Hg, or current treatment with antihypertensive medications. Hypertension control was defined as blood pressure levels of less than 140/90 mm Hg. RESULTS: A total of 9618 residents aged 35 years and above were included (response rate: 81.3%), and 19.7% residents were the Three Gorges migrants. The age-adjusted prevalence of hypertension was 37.3% for all, and 21.3%, 39.8%, 58.0% for aged 35 - 44, 45 - 59, >= 60 years, respectively. The age-adjusted rate was higher in men for all (39.1%) and aged 35 - 44 years (27.0%) than in women (36.3% for all and 17.8% for aged 35 - 44 years, P < 0.01). The age-adjusted rate of awareness, treatment and control rates of hypertension were lower in men (18.5%, 9.0%, 0.9%, respectively) than in women (23.5%, 13.6%, 2.0%, respectively, all P < 0.01). Among the participants with treated hypertension, the control rate of hypertension was only 17.0%. Prevalence and rate of awareness, treatment and control of hypertension were similar between migrants and non-migrants. CONCLUSION: The prevalence of hypertension is high, but the awareness, treatment, control rates were low in rural area of Yiling District. Efforts should be made to reduce the prevalence rate and to improve the control rate of hypertension in this area. PMID- 22321239 TI - [Clinical characteristics of congenital ventricular aneurysm and diverticula in inland China]. AB - OBJECTIVE: To summarize the clinical characteristics of congenital ventricular aneurysm and diverticula in inland China. METHODS: To identify the literature of congenital aneurysm and diverticula from Wanfang, China National Knowledge Infrastructure (CNKI) and PubMed databases, and to analyze the clinical characteristics of congenital aneurysm and diverticula from January of 2001 to December of 2009. RESULTS: A total of 116 patients [78 men, 1 - 80 (33.5 +/- 21.3) years old] with congenital aneurysm or diverticula were included in 109 articles. Twenty-five patients (13 men) were congenital ventricular aneurysm, including a family of 4 patients. Ninety-one patients (65 men) were congenital ventricular diverticula. One hundred patients were detected by echocardiography during medical examination, 34 patients combined with other cardiac anomalies, 4 of which with extracardiac structures. There were 8 patients with ventricular arrhythmia, 8 patients with thrombosis, 2 patients died of cardiac rupture, 4 patients died of sudden death, surgical operation was performed in 46 patients and 3 patients received ablation procedure. All patient did not receive implantable cardioverter defibrillator (ICD) implantation. CONCLUSIONS: Congenital ventricular aneurysm or diverticulum is a rare cardiac malformation. Most congenital left ventricular aneurysms and diverticula are asymptomatic and detected by echocardiography. Congenital ventricular aneurysm or diverticulum may cause ventricular tachycardia, ventricular wall rupture, systemic embolization or sudden death, which had to be treated individually. PMID- 22321240 TI - [Quadricuspid aortic valve with aortic insufficiency: a case report]. PMID- 22321241 TI - [Silent three vessel coronary disease first diagnosed as arterial embolism in the extremities: a case report]. PMID- 22321242 TI - [Association between microRNAs and lipids metabolism]. PMID- 22321243 TI - [An update for the research progress of osteoprotegerin on coronary artery disease]. PMID- 22321244 TI - Sulphur stable isotope systematics in diagenetic pyrite from the North Sea hydrocarbon reservoirs revealed by laser combustion analysis. AB - Our study focuses on pyrite nodules developed in the Brent Group sandstones, which host the Brent Oilfield, one of the North Sea's greatest oil and gas producers. Timing of nodule formation is equivocal, but due to the forceful, penetrative textures that abound, it is considered late. This pyrite offers a research opportunity because it records the development of the supply of H(2)S in a hydrocarbon reservoir and its sulphur isotopic composition. Laser-based analysis of delta(34)S reveals an extraordinary diversity in values and patterns. The values range from-27 to+720/00, covering half the terrestrial range, with large variations at the submillimetre scale. Isotopically heavy (delta(34)S ~+300/00 or higher) sulphide is endemic, but low delta(34)S pyrite is also present and appears to represent a temporally though not spatially (on the ~cm scale) distinct pyritisation event. The distribution of delta(34)S values within individual concretions can be normal (Gaussian), but in some cases may reflect progressive isotope fractionation process(es), conceivably of Rayleigh type. The source of the sulphur and the identity of the isotope fractionation process(es) remain enigmatic. PMID- 22321245 TI - Detection of collagen triple helix repeat containing-1 and nuclear factor (erythroid-derived 2)-like 3 in colorectal cancer. AB - BACKGROUND: Collagen Triple Helix Repeat Containing-1 (CTHRC1) and Nuclear factor (erythroid-derived 2)-like 3 (NFE2L3) may be useful biomarker candidates for the diagnosis of colorectal cancer (CRC) since they have shown an increase messenger RNA transcripts (mRNA) expression level in adenomas and colorectal tumours when compared to normal tissues. METHODS: To evaluate CTHRC1 and NFE2L3 as cancer biomarkers, it was generated and characterised several novel specific polyclonal antibodies (PAb), monoclonal antibodies (MAbs) and soluble Fab fragments (sFabs) against recombinant CTHRC1 and NFE2L3 proteins, which were obtained from different sources, including a human antibody library and immunised animals. The antibodies and Fab fragments were tested for recognition of native CTHRC1 and NFE2L3 proteins by immunoblotting analysis and enzyme-linked immunosorbent assay (ELISA) in colorectal cell lines derived from tumour and cancer tissues. RESULTS: Both, antibodies and a Fab fragment showed high specificity since they recognised only their corresponding recombinant antigens, but not a panel of different unrelated- and related proteins.In Western blot analysis of CTHRC1, a monoclonal antibody designated CH21D7 was able to detect a band of the apparent molecular weight of a full-length CTHRC1 in the human colon adenocarcinoma cell line HT29. This result was confirmed by a double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) with the monoclonal antibodies CH21D7 and CH24G2, detecting CTHRC1 in HT29 and in the colon adenocarcinoma cell line SW620.Similar experiments were performed with PAb, MAbs, and sFab against NFE2L3. The immunoblot analysis showed that the monoclonal antibody 41HF8 recognised NFE2L3 in HT29, and leukocytes. These results were verified by DAS-ELISA assay using the pairs PAb/sFab E5 and MAb 41HF8/sFab E5.Furthermore, an immunoassay for simultaneous detection of the two cancer biomarkers was developed using a Dissociation-Enhanced Lanthanide Fluorescent Immunoassay technology (DELFIA). CONCLUSIONS: In conclusion, the antibodies obtained in this study are specific for CTHRC1 and NFE2L3 since they do not cross-react with unrelated- and related proteins and are useful for specific measurement of native CTHRC1 and NFE2L3 proteins. The antibodies and immunoassays may be useful for the analysis of CTHRC1 and NFE2L3 in clinical samples and for screening of therapeutic compounds in CRC. PMID- 22321246 TI - Ornithine-delta-aminotransferase and proline dehydrogenase genes play a role in non-host disease resistance by regulating pyrroline-5-carboxylate metabolism induced hypersensitive response. AB - Non-host disease resistance involves the production of hypersensitive response (HR), a programmed cell death (PCD) that occurs at the site of pathogen infection. Plant mitochondrial reactive oxygen species (ROS) production and red ox changes play a major role in regulating such cell death. Proline catabolism reactions, especially pyrroline-5-carboxylate (P5C) accumulation, are known to produce ROS and contribute to cell death. Here we studied important genes related to proline synthesis and catabolism in the defence against host and non-host strains of Pseudomonas syringae in Nicotiana benthamiana and Arabidopsis. Our results show that ornithine delta-aminotransferase (deltaOAT) and proline dehydrogenases (ProDH1 and ProDH2) are involved in the defence against non-host pathogens. Silencing of these genes in N. benthamiana delayed occurrence of HR and favoured non-host pathogen growth. Arabidopsis mutants for these genes compromised non-host resistance and showed a decrease in non-host pathogen induced ROS. Some of the genes involved in proline metabolism were also induced by a pathogen-carrying avirulence gene, indicating that proline metabolism is influenced during effector-triggered immunity (ETI). Our results demonstrate that deltaOAT and ProDH enzyme-mediated steps produce ROS in mitochondria and regulate non-host HR, thus contributing to non-host resistance in plants. PMID- 22321247 TI - Nutritional hepatic iron overload is not prevented by parenteral hepcidin substitution therapy in mice. AB - The peptide hormone hepcidin functions as a negative regulator of intestinal Fe absorption and Fe recycling. Since its discovery as a systemic negative regulator of Fe metabolism, hepcidin has attracted enormous interest as a potential drug for the treatment and/or prevention of several forms of Fe overload. We therefore tested whether multiple doses of intraperitoneally administered synthetic renatured hepcidin can prevent hepatic Fe loading in mice concurrently fed an Fe rich diet, and whether the same treatment affects hepatic Fe stores in mice fed a normal diet. Cohorts of male mice were fed either a normal defined diet (180 parts per million Fe) or an Fe-rich diet (the same diet supplemented with 2 % carbonyl iron for 2 weeks). Concurrently, half of the animals in each diet group received 100 MUg of renatured hepcidin intraperitoneally every 12 h, for the same 2-week period. The second half of the animals received PBS only. The renatured synthetic hepcidin demonstrated biological activity by significantly decreasing transferrin saturation, which lasted for up to 24 h after a single hepcidin dose. However, the 14 d intraperitoneal hepcidin therapy did not prevent hepatic Fe overload in mice fed the Fe-rich diet, nor did it affect hepatic Fe stores in mice fed the normal diet. Both hepcidin agonists and antagonists are expected to have broad therapeutic potential. The absence of an effect of biologically active hepcidin on hepatic Fe loading shows the need for thorough future studies on the hepcidin regulation of Fe absorption and tissue distribution. PMID- 22321248 TI - Injury characteristics and outcome of road traffic crash victims at Bugando Medical Centre in Northwestern Tanzania. AB - BACKGROUND: Road traffic crash is of growing public health importance worldwide contributing significantly to the global disease burden. There is paucity of published data on road traffic crashes in our local environment. This study was carried out to describe the injury characteristics and outcome of road traffic crash victims in our local setting and provide baseline data for establishment of prevention strategies as well as treatment protocols. METHODS: This was a prospective hospital based study of road traffic crash victims carried out at Bugando Medical Centre in Northwestern Tanzania between March 2010 and February 2011. After informed consent to participate in the study, all patients were consecutively enrolled into the study. Data were collected using a pre-tested questionnaire and analyzed using SPSS computer software version 15.0. RESULTS: A total of 1678 road traffic crash victims were studied. Their male to female ratio was of 2.1:1. The patients ages ranged from 3 to 78 years with the mean and median of 29.45 (+/- 24.22) and 26.12 years respectively. The modal age group was 21-30 years, accounting for 52.1% patients. Students (58.8%) and businessmen (35.9%) were the majority of road traffic crash victims. Motorcycle (58.8%) was responsible for the majority of road traffic crashes. Musculoskeletal (60.5%) and the head (52.1%) were the most common body region injured. Open wounds (65.9%) and fractures (26.3%) were the most common type of injuries sustained. The majority of patients (80.3%) were treated surgically. Wound debridement was the most common procedure performed in 81.2% of the patients. The complication rate was 23.7%. The overall average length of hospital stay (LOS) was 23.5 +/- 12.3 days. Mortality rate was 17.5%. According to multivariate logistic regression analysis, patients who had severe trauma (Kampala Trauma Score II <= 6) and those with long bone fractures stayed longer in the hospital and this was significant (P < 0.001) whereas the age of the patient, severe trauma (Kampala Trauma Score II <= 6), admission Systolic Blood Pressure < 90 mmHg and severe head injury (Glasgow Coma Score = 3-8) significantly influenced mortality (P < 0.001). CONCLUSION: Road traffic crashes constitute a major public health problem in our setting and contribute significantly to unacceptably high morbidity and mortality. Urgent preventive measures targeting at reducing the occurrence of road traffic crashes is necessary to reduce the morbidity and mortality resulting from these injuries. Early recognition and prompt treatment of road traffic injuries is essential for optimal patient outcome. PMID- 22321249 TI - Evolving trends in the initial locoregional management of male breast cancer. AB - The locoregional management of breast cancer in men has evolved over time. Multimodality treatment regimens currently in use are based primarily on large randomized trials that exclusively enrolled women with breast cancer. We retrospectively reviewed cases of male breast cancer treated with radiotherapy at Stanford University Medical Center with an emphasis on 22 patients treated with surgery and locoregional radiotherapy. We report trends in the surgical techniques as well as in the use of adjuvant radiotherapy, chemotherapy, and hormonal therapy. There were no isolated locoregional failures in this cohort, and 5-year disease-free survival was 65%. The use of contemporary surgical and radiotherapeutic techniques in men is discussed. We conclude that treatment guidelines designed for women should be applied to the locoregional management of breast cancer in men. However, large international prospective registries and inclusion of men in cooperative group randomized trials will be important to confirm the safety and efficacy of modern treatment modalities for male breast cancer. PMID- 22321250 TI - New trends in nuclear spectrometry. AB - An overview on the status and function of current spectrometry hardware, of detectors having energy-dispersive (spectrometric) properties as well as of the latest developments in quantitative spectrometry software is presented. Making extensive use of modern computing power, new strategies in high-precision spectrum analysis have been developed which enhance the quality of results and also open new fields of spectrometric applications. Three principles have been newly introduced to spectrum analysis software: PMID- 22321251 TI - Prioritization methodology for the decommissioning of nuclear facilities: a study case on the Iraq former nuclear complex. AB - There are a number of sites in Iraq which have been used for nuclear activities and which contain potentially significant amounts of radioactive waste. The principal nuclear site being Al-Tuwaitha. Many of these sites suffered substantial physical damage during the Gulf Wars and have been subjected to subsequent looting. All require decommissioning in order to ensure both radiological and non-radiological safety. However, it is not possible to undertake the decommissioning of all sites and facilities at the same time. Therefore, a prioritization methodology has been developed in order to aid the decision-making process. The methodology comprises three principal stages of assessment: i) a quantitative surrogate risk assessment ii) a range of sensitivity analyses and iii) the inclusion of qualitative modifying factors. A group of Tuwaitha facilities presented the highest risk among the evaluated ones, followed by a middle ranking grouping of Tuwaitha facilities and some other sites, and a relatively large group of lower risk facilities and sites. The initial order of priority is changed when modifying factors are taken into account. It has to be considered the Iraq's isolation from the international nuclear community over the last two decades and the lack of experienced personnel. Therefore it is appropriate to initiate decommissioning operations on selected low risk facilities at Tuwaitha in order to build capacity and prepare for work to be carried out in more complex and potentially high hazard facilities. In addition it is appropriate to initiate some prudent precautionary actions relating to some of the higher risk facilities. PMID- 22321252 TI - Heterogeneous ribonucleoprotein K and thymidine phosphorylase are independent prognostic and therapeutic markers for oral squamous cell carcinoma. AB - Oral squamous cell carcinoma (OSCC) is the major cancer of head and neck with increasing incidence and mortality in Taiwan. We investigate hnRNP K, TP and FLIP expression and assess the prognostic and therapeutic potential of these markers in oral squamous cell carcinoma (OSCC). We analyzed hnRNP K, TP, and FLIP expression in 110 OSCC patients by immunohistochemistry. Statistical analyses were applied to correlate nuclear and cytoplasmic hnRNP K with elevated TP and FLIP, and to determine the associations of these three markers with clinicopathological manifestations, and assess their prognostic and therapeutic significance. The therapeutic implication of elevated TP was determined by measuring the sensitivity of OSCC cells to the TP-targeting drug, 5-fluoro-5' deoxyuridine (5'-DFUR). We found that each of these proteins was overexpressed in OSCC tumors. Nuclear hnRNP K and cytoplasmic hnRNP K were strongly associated with TP (r(2)=0.344, P=0.0004) and FLIP (r(2)=0.201, P=0.035), respectively. High hnRNP K and TP levels were associated with clinicopathological parameters predictive of poorer treatment outcome. Multivariate analyses indicated that cytoplasmic hnRNP K and TP are independent predictors of overall survival (P=0.022 and 0.009, respectively) and disease-free survival (P=0.012 and 0.005, respectively). OSCC cells expressing high levels of TP were more sensitive to treatment with 5'-DFUR. Elevated cytoplasmic hnRNP K and TP overexpression are associated with poorer survival in OSCC patients. In vitro experiments suggest that OSCC tumors with high levels of TP are more sensitive to 5'-DFUR treatment. Thus, cytoplasmic hnRNP K and TP may be potential prognostic and therapeutic markers for OSCC. PMID- 22321253 TI - The effect of CCND1 +870A>G and VEGF +936C>T polymorphisms on oral cancer development and disease-free survival in a Taiwan population. AB - The association between polymorphisms in vascular endothelial growth factor (VEGF) +936C>T and cyclin D1 (CCND1) +870A>G genes, oral cancer risk, and disease free survival remains controversial. We found no association between polymorphisms in the CCND1 and VEGF genes and oral cancer development using multivariate logistic regression analysis. Clinical data indicated that the VEGF +936C>T polymorphisms were associated with larger tumor size and advanced cancer stage, but the chi(2) test did not show that CCND1 polymorphisms were associated with larger tumor size and advanced cancer stage. However, Cox proportional hazards model analysis showed no correlation between the VEGF +936C>T polymorphisms and poor disease-free survival. The CCND1 +870A>G polymorphisms (hazard ratio (HR)=1.62, 95% CI=1.10-2.46; adjusted HR=1.63, 95% CI=1.08-2.54) and larger tumor size were associated with poor 5-year disease-free survival by the log rank test and multivariate Cox proportional hazards model analysis. We hypothesized that polymorphisms in CCND1 +870A>G and VEGF +936C>T genes are not correlated with the development of oral cancer. We found the CCND1 +870G allele to be an independent risk factor for poor 5-year disease-free survival in oral cancer patients. VEGF +936C>T polymorphisms were not directly correlated with poor survival, but they might be associated with increased tumor size, which affected our disease-free survival results. PMID- 22321254 TI - Concerns about serum androgens monitoring during testosterone replacement treatments in hypogonadal male athletes: a pilot study. AB - INTRODUCTION: A well-tailored testosterone replacement treatment (TRT) in male hypogonadal athletes plays a pivotal role to restore physiological performances, to reduce health risks, and to guarantee the ethic of competition. Few studies evaluated individual androgens profiles during TRT in trained individuals. AIM: The aim of this article was to verify the efficacy in restoring eugonadal serum and urinary androgens profiles after testosterone enanthate (TE) and gel (TG) administration. METHODS: Ten male Caucasian-trained volunteers affected by severe hypotestosteronemia (<8 nmol/L) were included. Serum androgens and urinary testosterone metabolites were evaluated, in the same subjects, before and weekly for 5 weeks after both a single intramuscular TE injection (250 mg) and during a daily administration of TG (50 mg/die of testosterone), respectively. MAIN OUTCOME MEASURES: The main outcome measures of this article were serum total testosterone (TT), dihydrotestosterone (DHT), calculated free and bioavailable testosterone (cFT, cBioT), 17-beta-estradiol, and urinary glucuronide testosterone metabolites. RESULTS: Supraphysiological TT concentrations were observed in 50% of our volunteers until 7 days after TE and in the 4% of total samples after TG. Serum DHT was high both after TE (all volunteers on day 7 and 50% on day 14) and during TG (32% of total samples). A relatively low number of samples showed normal cFT and cBioT both after TE and TG (20-44%, respectively). Urinary metabolites were related to the type of treatment and to serum androgens profile and resulted in the normal ranges from 15% to 60% of total samples. CONCLUSION: Besides well-known variations of mean serum TT, we showed a high percentage of serum and urinary samples with abnormal androgens, being TG safer than TE. We conclude that monitoring TRT with TT only may be inaccurate because of abnormal fluctuations of other circulating androgens. Further studies to identify the appropriate markers of eugonadism during TRT are highly warranted both in athletes and in non-athletes. PMID- 22321255 TI - Light and abscisic acid signalling are integrated by MIZ1 gene expression and regulate hydrotropic response in roots of Arabidopsis thaliana. AB - Plant roots undergo tropic growth in response to environmental cues, and each tropic response is affected by several environmental stimuli. Even its importance, molecular regulation of hydrotropism has not been largely uncovered. Tropic responses including hydrotropism were impacted by other environmental signal. We found that hydrotropism was reduced in dark-grown seedling. Moreover, we found that the expression of MIZ1, an essential gene for hydrotropism, was regulated by light signal. From our genetic analysis, phytochrome A (phyA)-, phyB and HY5-mediated blue-light signalling play curial roles in light-mediated induction of MIZ1 and hydrotropism. In addition, we found that abscisic acid (ABA) also induced MIZ1 expression. ABA treatment could recover weak hydrotropism and MIZ1 expression level of hy5, and ABA synthesis inhibitor, abamineSG, further reduced hydrotropic curvature of hy5. In contrast, ABA treatment did not affect ahydrotropic phenotype of miz1. These results suggest that ABA signalling regulates MIZ1 expression independently from light signalling. Our results demonstrate that environmental signals, such as light and stresses mediated by ABA signalling, are integrated into MIZ1 expression and thus regulate hydrotropism. These machineries will allow plants to acquire sufficient amounts of water. PMID- 22321256 TI - Higher perioperative morbidity and in-hospital mortality in patients with end stage renal disease undergoing nephrectomy for non-metastatic kidney cancer: a population-based analysis. AB - What's known on the subject? and What does the study add? Patients with renal failure more frequently harbour RCC due to predisposing factors such as cystic disease of the kidney. The benefit of nephrectomy might be outweighed by adverse perioperative events, however, which may be more prevalent in patients with end stage renal disease (ESRD). In a population-based study focusing on patients after non-elective colorectal surgery, patients with ESRD had an increased risk of mortality and complications. To date, small-scale studies have reported complication rates in patients with ESRD after nephrectomy for RCC with conflicting results. However, no formal contemporary analysis has been compiled within a nephrectomy cohort of adequate size. The present population-based case control study showed that patients with ESRD are at substantially higher risk of in-hospital mortality and in-hospital complications. Specifically, we demonstrated higher cardiac-related complications, transfusion and haemorrhage/haematoma rates in patients with ESRD than in others. Moreover, patients with ESRD are more likely to have prolonged length of stay in hospital, and incur higher hospital charges. Based on the findings of the present study, use of biopsy and active surveillance for small, carefully selected renal masses might be considered in patients with ESRD at high risk of morbidity and mortality after surgery. OBJECTIVE: To examine the effect of end-stage renal disease (ESRD) on six short-term nephrectomy outcomes. PATIENTS AND METHODS: The Nationwide Inpatient Sample was used to assess the rates of blood transfusions, intra operative and postoperative complications, length of hospital stay (LOS) within the highest quartile (>5 days), total hospital charges within the highest quartile (>$33 391) and in-hospital mortality. Propensity-based matching was performed to adjust for potential baseline differences between patients with ESRD and others. Multivariable logistic regression analyses further adjusted for confounding variables. RESULTS: Overall, 46 225 patients underwent open radical, open partial, laparoscopic radical or laparoscopic partial nephrectomy for non metastatic kidney cancer between 1998 and 2007. Of those, 941 patients with ESRD were identified (2.0%). For patients with ESRD and others, the following rates were recorded, respectively: blood transfusions, 17.4 vs 9.1% (P < 0.001); intra operative complications, 3.5 vs 3.3% (P = 0.81); postoperative complications, 19.2 vs 15.6% (P = 0.007); length of stay within the highest quartile, 55.4 vs 30.1% (P < 0.001); total hospital charges within the highest quartile, 50.4 vs 26.3% (P < 0.001); in-hospital mortality, 2.4 vs 0.5% (P < 0.001). In multivariable logistic regression analyses, patients with ESRD were more likely to receive a blood transfusion (odds ratio [OR] = 2.05, P < 0.001), to experience any postoperative complication (OR = 1.25, P = 0.019), to have a LOS within the highest quartile (OR = 3.06, P < 0.001), to have hospital charges within the highest quartile (OR = 3.10, P < 0.001), and to die during hospitalization (OR = 4.85, P < 0.001). CONCLUSIONS: Patients with ESRD are at substantially higher risk of adverse outcomes after nephrectomy. Most importantly, the in-hospital mortality rate is fivefold higher. PMID- 22321257 TI - Concrete under sulphate attack: an isotope study on sulphur sources. AB - The formation of secondary sulphate minerals such as thaumasite, ettringite and gypsum is a process causing severe damage to concrete constructions. A major key to understand the complex reactions, involving concrete deterioration is to decipher the cause of its appearance, including the sources of the involved elements. In the present study, sulphate attack on the concrete of two Austrian tunnels is investigated. The distribution of stable sulphur isotopes is successfully applied to decipher the source(s) of sulphur in the deteriorating sulphate-bearing minerals. Interestingly, delta(34)S values of sulphate in local groundwater and in the deteriorating minerals are mostly in the range from+14 to+27 0/00. These delta(34)S values match the isotope patterns of regional Permian and Triassic marine evaporites. Soot relicts from steam- and diesel driven trains found in one of the tunnels show delta(34)S values from-3 to+5 0/00, and are therefore assumed to be of minor importance for sulphate attack on the concretes. In areas of pyrite-containing sedimentary rocks, the delta(34)S values of sulphate from damaged concrete range between-1 and+11 0/00. The latter range reflects the impact of sulphide oxidation on local groundwater sulphate. PMID- 22321258 TI - Reconstructing normality: characteristics of staff interactions with forensic mental health inpatients. AB - Forensic psychiatry is an area of priority for the Danish Government. As the field expands, this calls for increased knowledge about mental health nursing practice, as this is part of the forensic psychiatry treatment offered. However, only sparse research exists in this area. The aim of this study was to investigate the characteristics of forensic mental health nursing staff interaction with forensic mental health inpatients and to explore how staff give meaning to these interactions. The project included 32 forensic mental health staff members, with over 307 hours of participant observations, 48 informal interviews, and seven semistructured interviews. The findings show that staff interaction is typified by the use of trust and relationship-enabling care, which is characterized by the establishment and maintenance of an informal, trusting relationship through a repeated reconstruction of normality. The intention is to establish a trusting relationship to form behaviour and perceptual-corrective care, which is characterized by staff's endeavours to change, halt, or support the patient's behaviour or perception in relation to staff's perception of normality. The intention is to support and teach the patient normal behaviour by correcting their behaviour, and at the same time, maintaining control and security by staying abreast of potential conflicts. PMID- 22321259 TI - Medications in patients treated with therapeutic plasma exchange: prescription dosage, timing, and drug overdose. AB - Therapeutic plasma exchange (TPE) is an extracorporeal process commonly used in clinical medicine for the treatment of a variety of neurological, renal, hematological, dermatological, and other diseases. Inherent to the procedure, patients' plasma removal may lead to the extraction of drugs they are concurrently receiving. This review discusses the published literature assessing TPE's influence on different drug classes' disposition and, when applicable, sets forth management recommendations in cases where the drugs are used at the usual doses and in cases of drug overdose. PMID- 22321260 TI - Inkjet printing of sol-gel synthesized hydrated tungsten oxide nanoparticles for flexible electrochromic devices. AB - Tungsten oxide nanoparticles were synthesized via a sol-gel route using metallic tungsten as precursor, and were printed on a flexible electrode using inkjet printing in order to build solid-state electrochromic cells. Several spectroscopic techniques were used to characterize and compare tungsten oxide particles obtained from different origins. FTIR, Raman and X-ray diffraction spectroscopic measurements showed that the sol-gel synthesis described here produces nanoparticles mainly in an amorphous state with hexagonal crystalline domains and allowed the analysis of the hydration extent of those nanoparticles. The size was measured combining dynamic light scattering, sedimentation, and microscopic techniques (AFM), showing a consistent size of about 200 nm. The tungsten oxide nanoparticles were used to produce an ink formulation for application in inkjet printing. Solid-state electrochromic devices were assembled at room temperature, without sintering the tungsten oxide printed films, showing excellent contrast between on/off states. Electrochemical characterization of those films is described using cyclic voltammetry. The devices were then tested through spectroelectrochemistry by Visible/NIR absorption spectroscopy (400-2200 nm range), showing a dual spectroscopic response depending on the applied voltage. This phenomenon is attributed to the presence of two different crystalline states in accordance with results obtained from the spectroscopic characterization of the nanoparticles. The electrochromic cells had a good cycling stability showing high reversibility and a cyclability up to more than 50,000 cycles with a degradation of 25%. PMID- 22321261 TI - The anatomy of the proximal radius: implications on fracture implant design. AB - BACKGROUND: The proximal radius features a complex anatomy. Several studies have been published on the anatomy using different technical approaches; however, most of these studies were conducted with a special focus on parameters relevant to radial prosthetic design. The purpose of our study was to explore the complex geometry of the proximal radius with regard to fracture implant design. METHODS: Our computed tomography-based measurements of 78 multiplanar reformatted radii allow for exact assessment of its geometry and offer a scientific rationale towards the design of fracture implants. We conducted measurements on the radial head, the radial neck, the radial tuberosity, the radial head-to-neck angle, and the safe zone. RESULTS: A wide range of normal anatomy has been demonstrated for all parameters. Sex differences are statistically significant in all registered parameters, except the radial head-to-neck angle. Although measurements of maximum vs minimum radial head, neck, and tuberosity diameters show close correlation, diameter-to-length correlations, such as radial head diameter vs radial head height and radial neck diameter vs radial neck length, are low. CONCLUSIONS: Besides the wide range in size, intraindividual parameter variations have to be taken into account in the design of anatomically precontoured plates. The results of this study indicate that these plates will still need to offer the ability of "bend to match." PMID- 22321262 TI - The EDLL motif: a potent plant transcriptional activation domain from AP2/ERF transcription factors. AB - In plants, the ERF/EREBP family of transcriptional regulators plays a key role in adaptation to various biotic and abiotic stresses. These proteins contain a conserved AP2 DNA-binding domain and several uncharacterized motifs. Here, we describe a short motif, termed 'EDLL', that is present in AtERF98/TDR1 and other clade members from the same AP2 sub-family. We show that the EDLL motif, which has a unique arrangement of acidic amino acids and hydrophobic leucines, functions as a strong activation domain. The motif is transferable to other proteins, and is active at both proximal and distal positions of target promoters. As such, the EDLL motif is able to partly overcome the repression conferred by the AtHB2 transcription factor, which contains an ERF-associated amphiphilic repression (EAR) motif. We further examined the activation potential of EDLL by analysis of the regulation of flowering time by NF-Y (nuclear factor Y) proteins. Genetic evidence indicates that NF-Y protein complexes potentiate the action of CONSTANS in regulation of flowering in Arabidopsis; we show that the transcriptional activation function of CONSTANS can be substituted by direct fusion of the EDLL activation motif to NF-YB subunits. The EDLL motif represents a potent plant activation domain that can be used as a tool to confer transcriptional activation potential to heterologous DNA-binding proteins. PMID- 22321263 TI - Construct validation theory applied to the study of personality dysfunction. AB - The authors review theory validation and construct validation principles as related to the study of personality dysfunction. Historically, personality disorders have been understood to be syndromes of heterogeneous symptoms. The authors argue that the syndrome approach to description results in diagnoses of unclear meaning and constrained validity. The alternative approach of describing personality dysfunction in terms of homogeneous dimensions of functioning avoids the problems of the syndromal approach and has been shown to provide more valid description and diagnosis. The authors further argue that description based on homogeneous dimensions of personality function/dysfunction is more useful because it provides direct connections to validated treatments. PMID- 22321264 TI - Chromosomally integrated human herpesvirus-6 in transplant recipients. AB - Human herpesvirus-6 (HHV-6) is unique among human herpesviruses because of its ability to integrate into chromosomes. This entity, termed chromosomally integrated HHV-6 (CIHHV-6), is often mistaken for active infection and treated unnecessarily. The clinical significance of CIHHV-6 in transplant recipients is not defined. Herein, the clinical characteristics of 7 liver transplant patients with CIHHV-6 from our recent study, together with 14 other published cases of CIHHV-6 were reviewed. Of the 21 cases, CIHHV-6B was reported most commonly among solid organ transplant recipients, while CIHHV-6A was mostly seen in allogeneic hematopoietic stem cell recipients. None of the 21 patients developed clinical symptoms related to HHV-6 after transplantation. However, antiviral therapy was administered to 5 asymptomatic patients mistaken to have HHV-6 infection because of their very high HHV-6 DNA levels, 3 who developed symptomatic cytomegalovirus disease, and 1 with graft-versus-host disease that was mistaken for HHV-6 infection. In patients who received antiviral therapy, there was no apparent decline in HHV-6 DNA load, although change in viral kinetics is difficult to discern in the setting of high baseline HHV-6 DNA load. Clinicians should be aware of this entity of CIHHV-6 so that antiviral therapy can be considered in the proper clinical context. PMID- 22321265 TI - Role of DNA methyltransferase 3A mRNA expression in Egyptian patients with idiopathic thrombocytopenic purpura. AB - INTRODUCTION: Idiopathic thrombocytopenic purpura (ITP) is an organ-specific autoimmune hemorrhagic disease characterized by breakdown of self-tolerance and triggering autoreactive lymphocytes' response against platelets. The underlying etiology of ITP remains largely unknown. DNA methylation plays an essential role in maintaining T-cell function, and impaired methylation can lead to inappropriate gene expression and contribute to T-cell autoreactivity and autoimmunity. The aim of this study was to evaluate the role of DNA methyltransferase 3A gene expression in the pathogenesis of ITP. METHODS: This study included 60 subjects: 20 healthy volunteers as a control group, 20 patients with acute ITP, and 20 patients with chronic ITP. DNA methyltransferase 3A (DNMT3A) mRNA expression in peripheral blood mononuclear cells was measured by real-time quantitative polymerase chain reaction. Plasma S-adenosylhomocysteine (SAH) levels were assayed with reversed-phase high-performance liquid chromatography. RESULTS: DNMT3A mRNA expression was significantly decreased in patients with ITP as compared with that of the control group. Plasma SAH level was significantly elevated in patients with ITP than in healthy controls. However, no significant difference was found in DNMT3A mRNA expression or plasma SAH level between patients with acute and chronic ITP. CONCLUSIONS: Aberrant DNA methylation status reflected by decreased mRNA expression of DNMT3A and increased plasma SAH level may play an important role in the pathogenesis of ITP, although the precise underlying mechanisms still await further investigations, and extensive work in this field is clearly needed to provide novel therapeutic targets for ITP. PMID- 22321266 TI - [Enhance specialist training and improve the capabilities of management on pulmonary vascular diseases in China]. PMID- 22321267 TI - [Follow application indication to avoid overuse of percutaneous coronary intervention procedure]. PMID- 22321268 TI - [Update on the standardized management of acute pulmonary embolism]. PMID- 22321269 TI - [Chinese expert consensus for septal myocardial ablation of hypertrophic obstructive cardiomyopathy]. PMID- 22321270 TI - [Pay more attention to imaging assessments in patients with pulmonary hypertension]. PMID- 22321271 TI - [Clinical characteristics and survival of patients with pulmonary veno-occlusive disease]. AB - OBJECTIVE: To investigate the clinical presentation, diagnosis, treatment and outcome of patients with pulmonary veno-occlusive disease (PVOD). METHODS: Data from patients diagnosed as PVOD from May 2008 to May 2011 in Shanghai Pulmonary Hospital, Tongji University were retrospectively reviewed. RESULTS: During this period, 5 patients [4 female, aged from 12 to 42 (22 +/- 12) years old] were diagnosed as PVOD. The durations from symptoms onset to PVOD diagnosis was 2 to 50 (16 +/- 20) months and four of them were previously diagnosed as idiopathic pulmonary arterial hypertension. All patients at the time of PVOD diagnosis had a severely impaired WHO pulmonary hypertension functional class (3 in class III and 2 in class IV). Furthermore, all patients characterized by a typical sign of centrilobular ground-glass opacities in high-resolution computed tomography, a markedly reduction of diffusing capacity of the lung for carbon monoxide [(38 +/- 12)% of predicted value] in pulmonary functional test and severely compromised cardio-pulmonary hemodynamics identified by right heart catheterization. All patients received conventional and pulmonary arterial hypertension specific therapies, and then followed-up regularly. Up to now, 4 out of 5 patients died due to refractory right heart failure. The durations from symptoms onset to death and from PVOD establish to death were 5 - 65 (27 +/- 26) months and 1 - 16 (9 +/- 9) months, respectively. CONCLUSIONS: PVOD is a rare and malignant cardio pulmonary disorder that often be misdiagnosed as idiopathic pulmonary arterial hypertension. Given the poor responses to modern pulmonary arterial hypertension specific therapies, lung transplantation remains the treatment of choice. PMID- 22321272 TI - [Determination of pulmonary vascular resistance by improved right heart catheter in rat]. AB - OBJECTIVE: To establish an easy and repeatable method for determination of pulmonary vascular resistance in normal and pulmonary arterial hypertension (PAH) rats. METHODS: Forty-five Sprague-Dawley rats were randomly assigned into three groups: control group, low dose monocrotaline (MCT) group (50 mg/kg) and high dose MCT group (60 mg/kg). Rats in PAH groups received single subcutaneous injection of MCT. We measured pulmonary artery pressure by right heart catheterization using an improved hand-made PE-50 catheter. Cardiac output was calculated through thermodilution method. Pulmonary vascular resistance equals the mean pulmonary artery pressure divided by cardiac output. RESULTS: The total percentages of success to detect pulmonary artery pressure, cardiac output and pulmonary vascular resistance were 98%, 100% and 96% respectively in 3 groups. Twenty-one days after MCT injection, mean pulmonary artery pressure significantly increased in MCT group compared to control group [(43.1 +/- 0.8), (54.8 +/- 2.2) vs. (17.4 +/- 1.0) mm Hg (1 mm Hg = 0.133 kPa), P < 0.001], and the mPAP was also significantly higher in high dose MCT group than in low dose MCT group (P < 0.001). Cardiac output was significantly lower in PAH rats than in control rats [(77.5 +/- 6.9), (71.0 +/- 6.7) vs. (126.8 +/- 3.9) ml/min, P < 0.001]. Pulmonary vascular resistance was significantly increased in PAH rats compared with control rats [(0.56 +/- 0.06), (0.76 +/- 0.08) vs. (0.13 +/- 0.01) mm Hg*min(-1)*ml(-1), P < 0.001]. There were significant differences in both MCT-treated groups (P = 0.01). CONCLUSIONS: Pulmonary vascular resistance in rats could be reliably detected using the improved hand-made PE-50 right heart catheter. PMID- 22321273 TI - [Establishment of a cyanotic congenital heart defect porcine model with decreased pulmonary blood flow]. AB - OBJECTIVE: To establish a porcine model of congenital heart disease with decreased pulmonary blood to explore the morphological changes of immature pulmonary vascular vessels. METHODS: Twenty piglets (one to two-month-old) were randomly divided into three groups: sham-operated group (group S, n = 6), small incisions on the right chest, produced a transient reduction in pulmonary blood; Operation group 1(group T(1), n = 7), small incisions on the right chest, producing artificial atrial defect with self-made dilator and simultaneous banding pulmonary artery to generate a systolic pressure gradient between 20 - 30 mm Hg (1 m Hg = 0.133 kPa); Operation group 2(group T(2), n = 7): operation procedure was similar as group T(1) with systolic pressure gradient between 30 - 50 mm Hg. Lung tissue from right middle lobe (1.0 cm*0.8 cm*0.8 cm) was taken immediately after thoracotomy, at the end of surgery and at 2 months after operation and stained by Weigert (elastic fiber) and van Gieson (collagen) methods to observe the morphological changes. RESULTS: Five animals survived in Group S, 6 animals survived in group T(1) and 5 animals survived in group T(2). The inside diameter of pulmonary arterioles after thoracotomy and at the end of surgery was similar among the three groups (P > 0.05). At 2 months after operation, the inside diameter of pulmonary artery was significantly higher in group T(1) and T(2) than in group S (all P < 0.05) while the number of pulmonary small artery per square centimeter (APSC) of group T(1) and T(2) was significantly lower than that of group S (all P < 0.05). Tunica media of pulmonary artery was thinner and vascular lumen was larger in group T(1) and T(2) compared to those of group S. CONCLUSION: In this piglets model with reduced pulmonary blood, the pulmonary arterioles underwent dysplastic changes. Thus, pulmonary blood flow is an important determinant for the physiological development of pulmonary artery. PMID- 22321274 TI - [Novel mutations of cardiac troponin T in Chinese patients with hypertrophic cardiomyopathy]. AB - OBJECTIVE: To screen the cardiac troponin T (TNNT2) mutations in Chinese patients with hypertrophic cardiomyopathy (HCM) and to analyze the potential link between the genotype and the phenotype. METHODS: Clinical features of 100 probands with HCM and some family members were evaluated, 200 unrelated normal subjects served as control. The exons and flanking introns of TNNT2 were amplified with PCR and direct sequencing was used to screen TNNT2 mutations/polymorphisms. RESULTS: Two novel missense mutations were detected in 2 HCM patients: R92W and R286H. These 2 mutations were not found in 200 non-HCM controls. A five-basepair insertion/deletion polymorphism in intron 3 of TNNT2 was identified in this HCM cohort but was not related to the phenotype. CONCLUSIONS: Two missense mutations, R92W and R286H, were found in 2/100 patients with HCM, TNNT 2 mutation is relatively low in Chinese patients with HCM. PMID- 22321275 TI - [Value of cardiac magnetic resonance imaging for the diagnosis of cardiac amyloidosis]. AB - OBJECTIVE: To observe the clinical features and cardiac magnetic resonance imaging (CMR) characteristics of patients with endomyocardial biopsy (EMB)-proven cardiac amyloidosis (CA). METHODS: EMB proven CA patients underwent CMR examination from September 2006 to December 2010 were included. The findings of clinical manifestation, electrocardiogram, echocardiography and CMR were analyzed. RESULTS: Among the 18 patients with EMB verified CA, 5 patients underwent CMR. All 5 patients had heart failure symptoms and electrocardiogram was abnormal. Echocardiogram showed concentric left ventricular hypertrophy, granular appearance of the myocardium, left atrial enlargement and moderate to severe left ventricular diastolic dysfunction. CMR revealed increased thickness of the left ventricular wall (especially at the inter-ventricular septum), enlarged bilateral auricle, restricted left ventricular filling with normal or mild to moderate reduced systolic function. Pleural and pericardial effusions were observed in 2 patients. Abnormal late gadolinium enhancement (LGE) was detected in all 5 patients. CMR revealed different patterns of LGE. Left ventricular global subendocardial delayed gadolinium enhancement or transmural delayed gadolinium enhancement were found, and patients also showed line-, granular- or patchy-like enhancement. The degree and range of LGE paralleled the disease course and were consistent with electrocardiogram changes. CONCLUSIONS: As a noninvasive diagnostic tool, CMR is valuable in the diagnosis of CA. For patients with clinical suspicion of CA, CMR could be a helpful diagnostic tool, especially in the hospitals where EMB is not available. PMID- 22321276 TI - [Left ventricular longitudinal rotation changes in patients with dilated cardiomyopathy detected by two-dimensional speckle tracking imaging]. AB - OBJECTIVE: To assess the left ventricular longitudinal rotation (LR) in patients with dilated cardiomyopathy (DCM). METHODS: Conventional echocardiography (GE Vivid7) was performed in 35 healthy subjects and 42 DCM patients. Left atrial diameter was measured by M-mode echocardiography, left ventricular end-systolic, end-diastolic volume and left ventricular ejection fraction (LVEF) were calculated by bi-plane simpson's method. The peak velocity during early diastole (Ve) and late diastole (Va) of anterior mitral valve were measured by pulse-waved doppler, and the ratio Ve/Va was calculated. The peak radial systolic strain, strain rate in systolic, early and late diastolic periods were measured. Segmental LR and global LR were assessed using two-dimensional speckle tracking imaging (2D-STI). RESULTS: The peak radial systolic strain, strain rate in systolic, early and late diastolic periods in DCM group were significantly lower than in healthy subjects, the rotation degrees of the middle and base lateral, the apex and the base septum walls were significantly lower than those of the healthy subjects. A prominent counterclockwise LR (0.76 degrees +/- 2.63 degrees ) was shown in healthy subjects while prominent clockwise LR (-1.58 degrees +/- 3.42 degrees ) was present in DCM patients. The time delay between the left ventricular lateral wall and the base septum wall in DCM patients significantly correlated with the peak LR of the left ventricular (r = 0.409, P < 0.01; r = 0.396, P < 0.01). CONCLUSIONS: 2D-STI can be used to assess the LR in DCM patients and a clockwise LR is present in DCM patients which might be caused by the time delay between the left ventricular lateral wall and the base-septum wall. PMID- 22321277 TI - [Aspirin response and related factors in aged patients]. AB - OBJECTIVE: To explore clinical and laboratory factors associated aspirin response, and the association between gastrointestinal bleeding and aspirin response in aged patients. METHODS: A total of 136 patients aged 60 and over [mean age (74.9 +/- 7.0) years] with ischemic heart disease and at high risk for ischemic heart disease were included. Arachidonic acid induced platelet aggregation (AA-Ag) was measured before and at 7(th) day after taking aspirin (100 mg/d). Patients were followed for 6 months and incidence of gastrointestinal bleeding was obtained. RESULTS: Post-treatment AA-Ag was significantly reduced compared to baseline (13.29% +/- 5.52% vs. 73.20% +/- 7.32%, P < 0.05). A heterogeneous distributed post-treatment AA-Ag was observed (range 0.42% to 30.50%). Post-treatment AA-Ag was positively correlated with baseline AA-Ag (r = 0.493, P < 0.01). The level of post-treatment AA-Ag was significantly higher in the fourth quartile group at baseline than in the others quartile groups at baseline. Patients aged 80 years and over had significantly lower post-treatment AA-Ag (10.25% +/- 4.68%) compared with patients of 60 - 69 years (13.96% +/- 5.20%) and of 70 - 79 years (13.73% +/- 5.48%, all P < 0.01). The incidence of patients in the lowest quartile of post-treatment AA-Ag was significantly higher in patients >= 80 years (38.24%) than in patients of 60 - 69 years (11.1%) and of 70 - 79 years (24.0%). Multiple variable analysis revealed post-treatment AA-Ag was significantly influenced by baseline AA-Ag, >= 80 years old, diabetes mellitus and acute coronary syndrome. We observed 4 (2.9%) mild gastrointestinal bleeding during follow up. Post-treatment AA-Ag was in the lowest quartile in 3 patients with mild gastrointestinal bleeding. CONCLUSIONS: Increased baseline platelet reactivity as well as diabetes mellitus and acute coronary syndrome are associated with low aspirin response in the aged patients. Aspirin response is significantly higher in very old patients. PMID- 22321278 TI - [Impact of CYP2C9 and VKORC1 polymorphism on warfarin response during initiation of therapy]. AB - OBJECTIVE: To investigate potential contributions of genetic variants of cytochrome P-450 2C9 (CYP2C9) and vitamin K expoxide reductase (VKORC1) to the anticoagulation response during the initiation of warfarin therapy in the Han Chinese population. METHODS: A total of 798 Han Chinese patients received long term warfarin anticoagulant therapy orally after valve replacement in our hospital between 2000 and 2008 were included in this study. Nine single nucleotide polymorphism (SNP) loci [rs12572351 G > A, rs9332146 G > A, rs4917639 G > T, rs1057910 A > C (CYP2C9(*)3), rs1934967 G > T, rs1934968 G > A, rs9923231 C > T (VKORC1-1639 G > A), rs2359612 G > A and rs10871454 C > T] in 2 genes including CYP2C9 and VKORC1, which were possibly correlated with warfarin pharmacokinetics and pharmacodynamics through literature retrieval, were selected and analyzed. Warfarin steady-state dose requirement, time to the INR (the international normalized ratio) within the therapeutic range and percent of the INR of more than 3.5 were compared among genotype subgroups. SNaPshot technique was used to detect gene SNPs; Hardy-Weinberg genetic equilibrium test was used to test population representativeness. RESULTS: CYP2C9(*)3 genotype did not affect the required warfarin dose while it was associated with increased risk of bleeding when treated with routine dosage regimen during the initiation of treatment. The allelic mutation frequency at VKORC1 gene rs10871454G > A and VKORC1-1639G > A SNP loci was 92.04% and 88.03%, respectively and rs10871454 was in perfect linkage disequilibrium with-1639. Patients with VKORC1 rs10871454 genetic mutation required lower warfarin dose in the first 28 days of therapy. VKORC1-1639 genetic polymorphism was also associated with shorter time to the INR within the therapeutic range and increased risk of over-anticoagulation. CONCLUSION: Detecting genetic polymorphism of CYP2C9 and VKORC1 could guide clinical use of warfarin to reduce the risk of adverse reactions including bleeding in patients receiving chronic anticoagulation therapy. PMID- 22321279 TI - [The efficacy and safety of tolvaptan on treating heart failure patients with hyponatremia]. AB - OBJECTIVE: To evaluate the efficacy and safety of tolvaptan on treating congestive heart failure patients with hyponatremia. METHODS: This randomized double-blind placebo-controlled multicenter trial enrolled 65 patients with congestive heart failure and hyponatremia. On top of standard therapy, patients were randomized to receive either tolvaptan 15 - 60 mg daily or placebo according to the serum sodium concentration. The primary end points were the change of average daily serum sodium concentration from baseline to day 4 and to day 7 respectively. Patients' weight, urine volume, sign of heart failure, heart function, blood pressure, heart rate, and all adverse events were observed. RESULTS: The daily serum sodium concentration increase was significantly higher in tolvaptan group than in placebo group during the first 4 days [(5.6 +/- 3.5) mmol/L vs. (2.5 +/- 3.4) mmol/L, P < 0.05] and 7 days [(5.9 +/- 3.5) mmol/L vs. (2.8 +/- 3.3) mmol/L, P < 0.05]. Moreover, urine volume increase and body weight decrease were more significant in tolvaptan group than in placebo group (all P < 0.05). The change of sign of heart failure, heart function, blood pressure and heart rate was similar between two groups (P > 0.05). There were more drug related adverse events of thirst (11.4%) and hypernatremia (5.7%) in Tolvaptan group. One patient in tolvaptan group developed agranulocytosis during therapy period and recovered post therapy. CONCLUSIONS: Tolvaptan could effectively increase serum sodium concentration, urine volume, and improve liquid balance in heart failure patients with hyponatremia. Tolvaptan related serious adverse event was low and could be well tolerated by patients tested in this cohort. PMID- 22321280 TI - [Association between systemic inflammation and autoimmunity parameters and plasma lipid in patients with rheumatoid arthritis]. AB - OBJECTIVE: The purpose of this study was to observe the association between inflammation status/autoimmune antibodies and plasma lipid in patients with rheumatoid arthritis (RA). METHODS: A total of 402 RA patients were admitted into our hospital during January 2008 to March 2009 and 225 RA patients who met the inclusion criteria were selected to perform a full lipid profile examination including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti cyclic citrullinated peptide (anti-CCP), anti-keratin antibody (AKA), anti perinuclear factor autoantibody (APF) and complement (C) were also evaluated. Atherogenic index of plasma (AIP) was calculate by the formula Log (TG/HDL-C). RESULTS: (1) There were 12.9%, 10.2% and 14.2% patients with elevated TC, LDL-C and TC respectively, patients with reduced HDL-C accounted for 43.6%. (2) C(3) was higher in elevated TC group than normal TC group (P < 0.05). ESR and CRP were significantly higher in decreased HDL-C group than in normal HDL-C group (P < 0.05). CRP, C(3) and C(4) were significantly higher in elevated LDL-C group than in normal LDL-C group (P < 0.05). (3) Multiple stepwise regression analysis showed that C(3) was positively correlated with TC (R(2) = 0.067, P < 0.05). Both ESR and CRP were negative correlated with HDL-C (R(2) = 0.202, P < 0.05). CRP and anti-CCP were positively correlated with LDL-C (R(2) = 0.129, P < 0.05). ESR and C(4) were positively correlated with AIP (R(2) = 0.046, P < 0.05). CONCLUSION: This study showed that rheumatoid arthritis is associated with an abnormal lipid profile, especially in patients with increased inflammation markers and autoimmune antibodies. Moreover, ESR and C(4) were predictors of increased AIP in this cohort. PMID- 22321281 TI - [Resveratrol improves coronary collateral circulation in pigs with experimental acute coronary occlusion]. AB - OBJECTIVE: To evaluate the impact of resveratrol on coronary collateral circulation in pigs suffered from experimental acute coronary occlusion. METHODS: Eighteen healthy pigs were randomly divided into 3 groups: resveratrol group, nitroglycerin group and control group. Animal model of acute coronary occlusion was established through PTCA method, and the blood flow spectrum in the left circumflex artery (LCX) was detected using intracoronary Doppler ultrasound. RESULTS: The average peak velocity (APV) in infarction correlation artery (IRA) was significantly decreased immediately after coronary occlusion [(0.85 +/- 0.25) cm/s vs. (24.83 +/- 3.43) cm/s, P < 0.05]. The APV remained unchanged during 0, 30 and 60 minutes after the occlusion. Reversed or bidirectional blood flow was observed and the APV increased significantly [(9.22 +/- 0.80) cm/s vs. (0.84 +/- 0.21) cm/s, (8.93 +/- 1.28) cm/s vs. (0.86 +/- 0.26) cm/s respectively, P < 0.05] after the coronary injection of resveratrol (2 mg) or nitroglycerin (0.3 mg). There was no significant difference in peak APV between the resveratrol and nitroglycerin groups. The duration of increased APV was significantly longer in resveratrol group than that in nitroglycerin group [(58.83 +/- 6.15) min vs. (21.80 +/- 5.79) min, P < 0.05]. CONCLUSIONS: The collateral circulation after acute coronary occlusion was obviously insufficient in pigs. Resveratrol could significantly improve the blood flow in coronary collateral circulation after acute occlusion in this model. PMID- 22321282 TI - [Association between overweight, obesity and arterial stiffness in community residents]. AB - OBJECTIVE: To evaluate the relationship between overweight, obesity and arterial stiffness in community residents. METHODS: A total of 4585 community-dwelling adults in Jiangsu province, China were surveyed with the method of stratified and cluster sampling from 2007 to 2009. Overweight and obesity were defined by body mass index (BMI) and arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). Statistical analysis of arteriosclerosis included multivariate logistic regression testing among which BMI was viewed as continuous variable (1 kg/m(2) increasing to BMI) and categorical variables (underweight, normal, overweight and obesity) respectively. Odds ratio, population attributable risk percent and the optimal cut-off points for BMI to evaluate arteriosclerosis were analyzed using receiver operator characteristic (ROC) curve. RESULTS: (1) After age control, BMI of male or female were positively correlated with baPWV (r = 0.213, P < 0.01; r = 0.186, P < 0.01). baPWV and prevalence of arteriosclerosis were significantly higher in obese residents compared with normal body weight group (all P < 0.01). (2) As a continuous variable, the odds ratio value of BMI on predicting arteriosclerosis was 1.146 (95%CI: 1.117 - 1.175, P < 0.01) after adjusting of age, gender and hypertension. As categorical variables, the odds ratio value of BMI was 0.369 (95%CI: 0.141 - 0.962, P < 0.05) for underweight group, 1.576 (95%CI: 1.333 - 1.863) for overweight group and 2.087 (95%CI: 1.615 2.698) for obesity group (all P < 0.01). (3) The population attributable arteriosclerosis risk was 19.1% and 11.6% in overweight and obesity groups, respectively. The area under the ROC curve was 0.661 (95%CI: 0.645 - 0.678, P < 0.01) and the optimal cut-off point for BMI to evaluate arteriosclerosis was 24.25 kg/m(2). CONCLUSIONS: Overweight and obese residents faced higher risk for arteriosclerosis than normal population. Overweight and obesity are independent risk factors for arteriosclerosis after adjusting for age, gender and hypertension. PMID- 22321283 TI - [Association between marital status and prevalence of peripheral arterial disease among Beijing residents: a cross-sectional study]. AB - OBJECTIVE: To investigate the relationship between marital status and prevalence of peripheral arterial disease (PAD) among Beijing residents. METHODS: From May to August 2007, 10 054 residents were interviewed to collect demographic and biochemistry information. Generalized linear mixed model was used to determine the relationship between marital status and prevalence of PAD in terms of OR and corresponding 95% confidence intervals. RESULTS: After adjusting the traditional risk factors including age, area, lipid, serum glucose, blood pressure, central obesity, smoking, drinking and physical activities for PAD, relationship between marital status and prevalence of PAD was found both at the female and male groups of those with 45 years or older. Compared with married men, OR and 95% confidence interval of PAD for unmarried men were 1.56 (0.39 - 6.35) and 1.61 (0.77 - 3.35) for those with 45 years younger and older respectively, while compared with married women, OR and 95% confidence interval of PAD for unmarried women were 0.75 (0.22 - 2.57) and 1.78 (1.23 - 2.58) for those with 45 years younger and older respectively. Significant differences (all P < 0.01) were found between married and unmarried women of 45 years or older in terms of age, waist circumstances, systolic blood pressure, fasting glucose, total cholesterol, low density lipoprotein and smoking. CONCLUSIONS: Peripheral arterial disease was related to marital status for women of 45 years or older among Beijing residents. Estrogen level and the distribution of other PAD risk factors might contribute to the observed finding. PMID- 22321284 TI - [The current therapy of right ventricular dysfunction in pulmonary arterial hypertension]. PMID- 22321285 TI - [Update on apical hypertrophic cardiomyopathy]. PMID- 22321286 TI - [Potential link between follistatin-like protein and cardiovascular diseases]. PMID- 22321287 TI - Can a river heal itself? Natural attenuation of metal contamination in river sediment. AB - Sediment sampling of bed sediment from a large river contaminated by mining and smelting was used to determine rates of natural attenuation of metal concentrations. A "natural decay model" was developed from high-resolution temporal data and used to predict when restoration guidelines would be met without restoration and with various degrees of restoration success. The natural decay model estimates that in the most contaminated reaches it will take about 90 years for average concentrations of As, Cd, Cu, Pb, and Zn to fall below "probable effects concentrations" (PEC), i.e. levels above which we expect to see adverse environmental effects. At sites farther downstream, all metals will fall below PEC in <35 +/- 8 years. It will take longer to reach "threshold effects concentrations" (TEC), i.e. concentrations at which no effects are expected. But, even in the most contaminated reaches, Cd, Pb, and Zn will reach TEC in <80 +/- 57 years, while Cu and As will take ~200 years. Model simulations with different levels of remediation success show that recovery is highly dependent on source reduction and how far the goal is from the basin background concentration. Furthermore, beneficial effects of restoration may be unexpectedly small: for example a likely decrease of ~20% in the source concentration would shorten the time to reach the Cu PEC by only 13 years. We argue that conducting analyses like these can provide insight into remediation approaches and ultimately decrease the cost of restoration by identifying the role of natural attenuation in restoration design and implementation. PMID- 22321289 TI - BJN gets a new sister! PMID- 22321288 TI - Combination of probenecid-sulphadoxine-pyrimethamine for intermittent preventive treatment in pregnancy. AB - The antifolate sulphadoxine-pyrimethamine (SP) has been used in the intermittent prevention of malaria in pregnancy (IPTp). SP is an ideal choice for IPTp, however, as resistance of Plasmodium falciparum to SP increases, data are accumulating that SP may no longer provide benefit in areas of high-level resistance. Probenecid was initially used as an adjunctive therapy to increase the blood concentration of penicillin; it has since been used to augment concentrations of other drugs, including antifolates. The addition of probenecid has been shown to increase the treatment efficacy of SP against malaria, suggesting that the combination of probenecid plus SP may prolong the useful lifespan of SP as an effective agent for IPTp. Here, the literature on the pharmacokinetics, adverse reactions, interactions and available data on the use of these drugs in pregnancy is reviewed, and the possible utility of an SP probenecid combination is discussed. This article concludes by calling for further research into this potentially useful combination. PMID- 22321290 TI - Thymic hyperplasia in a patient with Grave's disease. AB - Hyperplastic changes of the thymus may be found in patients with Graves' disease. However, this rarely presents as an anterior mediastinal mass, particularly among adults. In this report, we describe a 46-year old woman with Graves' disease and thymic hyperplasia. PMID- 22321291 TI - Predicting division plane position and orientation. AB - Predicting cellular behavior is a major challenge in cell and developmental biology. Since the late nineteenth century, empirical rules have been formulated to predict the position and orientation of mitotic cleavage planes in plant and animal cells. Here, we review the history of division plane orientation rules and discuss recent experimental and theoretical studies that refine these rules and provide mechanistic insights into how division can be predicted. We describe why some of these rules may better apply to certain cell types and developmental contexts and discuss how they could be integrated in the future to allow the prediction of division positioning in tissues. PMID- 22321292 TI - Sexual function and distress in women treated for primary headaches in a tertiary university center. AB - INTRODUCTION: Primary headaches are common in women and impact on their quality of life and psychosocial functioning. Few data are available on sexuality in female headache sufferers. AIM: An observational pilot study was conducted to assess sexual function and distress in women treated for primary headaches in a tertiary university center. METHODS: From a total of 194 women consecutively observed over a 3-month period, 100 patients were recruited. Migraine with and without aura, and tension-type headache, both episodic and chronic (CTTH), were diagnosed according to the International Classification of Headache Disorders. A detailed pharmacological history was collected, and anxiety and depression were assessed using validated scales. The Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised were administered. MAIN OUTCOME MEASURES: The main outcome measures are sexual symptoms and distress in women treated for primary headaches. RESULTS: More than 90% of the women had a median FSFI full scale score under the validated cutoff, while 29% reported sexual distress. Hypoactive sexual desire disorder (HSDD) was diagnosed in 20% of the women and the pain domain score (median 2, score range 0-6) was highly affected by the head pain condition. However, the FSFI domain and full-scale scores did not significantly differ by headache diagnosis. The women with CTTH displayed a high rate of sexual distress (45.5%) and a strong negative correlation between desire, arousal, and full-scale FSFI score and number analgesics/month (r: -0.77, P=0.006; r: -0.76, P=0.006; and r: -0.68, P=0.02, respectively). Depression was positively correlated with sexual distress (r: 0.63, P=0.001) only in the women with CTTH. CONCLUSION: Women treated for primary headaches were found to display a high rate of sexual symptoms and distress. Both migraine and tension-type headache were associated with sexual pain and HSDD, but women with CTTH seem to be more prone to develop sexual distress. PMID- 22321293 TI - Prevalence, populations and pheno- and genotypic characteristics of Listeria monocytogenes isolated from ready-to-eat vegetables marketed in Sao Paulo, Brazil. AB - Listeria monocytogenes is a foodborne pathogen of great concern due to the high fatality rates of listeriosis. The consumption of RTE vegetables has increased in Brazil over the last two decades, but little is known about the risks associated to the consumption of these products. This study evaluated the prevalence and counts of L. monocytogenes in 512 packages of ready-to-eat vegetables marketed in Sao Paulo. The isolates were characterized for their serotypes, ribotypes, positivity for virulence genes inlA, inlC and inlJ, resistance to chlorine, growth rate variability and capability to form biofilm on stainless steel (AISI 304, #4) coupons. L. monocytogenes was detected in 3.1% of the samples. Only five samples presented countable levels, with counts between 1.0*10(1) and 2.6*10(2)CFU/g. Isolates belonged to serotypes 1/2b or 4b and most were positive for genes inlC and inlJ. Ribotypable isolates were grouped into four groups: 1038 (69.4%), 19175 (11.3%), 19191 (17.7%) and 18604 (one isolate). Most isolates survived to exposure to 125 ppm of a chlorine-based disinfectant for 3 min. All isolates were capable to attach to the coupons, reaching counts above 4 log(10) CFU/cm(2) and the growth rate (MU) at 25 degrees C of the majority of the isolates varied between 0.1 and 0.2 log OD/h, but for few strains the MU was as high as 0.26 log OD/h. Results of this survey indicate that RTE vegetables may be vehicles of L. monocytogenes strains with limited variation in serotype, ribotype and virulence factors but varying significantly in resistance to chlorine disinfectants, capability of forming biofilm and growth rate. Data obtained is of foremost importance to serve as baseline for the development of scientific-based policies to control the incidence of L. monocytogenes in RTE vegetables in Brazil. PMID- 22321294 TI - Evidence for a dual versus single origin of the MMNs evoked by cued versus cueless deviants. AB - OBJECTIVE: This study was designed to separately test the effect of the cued/cueless nature of deviant stimuli and that of temporal distance between sound and deviance onsets on the mismatch negativity (MMN) as well as to look for discrepancies between behavioural discrimination performances and MMN amplitude when deviants are cueless. METHODS: Ten healthy adults passively listened to stimuli that were contrasted by the presence or absence of a frequency sweep starting early or late within the sound. Discrimination performances were collected after the electrophysiological sessions. RESULTS: MMNs were much larger for cued than for cueless deviants. The temporal distance between sound and deviance onsets affected MMNs evoked by both cued and cueless deviants, even to the point of abolishing the MMN when cueless deviance occurred late in the stimulus. Behavioural data were at ceiling levels for all conditions, contrasting with the absence of MMN evoked by cueless deviants with late onset. CONCLUSIONS: Two mechanisms contribute to the MMN evoked by cued deviants: the memory comparison process and the adaptation/fresh-afferent one. Within the temporal window of integration, the delay at which each component disappears is different. SIGNIFICANCE: Comparing waveforms evoked by cued versus cueless deviants provides a fairly simple way of isolating the MMN memory-based component. PMID- 22321295 TI - Statistical evaluation of recurrence quantification analysis applied on single trial evoked potential studies. AB - OBJECTIVE: We evaluated the potential of recurrence quantification analysis (RQA) to improve the analysis of trial-by-trial-variability in event-related potentials (ERPs) experiments. METHODS: We use an acoustic oddball paradigm to compare the efficiency of RQA with a linear amplitude based analysis of single trial ERPs with regard to the power to distinguish responses to different tone types. We further probed the robustness of both analyses towards structured noise induced by parallel magnetic resonance imaging (MRI). RESULTS: RQA provided robust discrimination of responses to different tone types, even when EEG data were contaminated by structured noise. Yet, its power to discriminate responses to different tone types was not significantly superior to a linear amplitude analysis. RQA measures were only moderately correlated with EEG amplitudes, suggesting that RQA may extract additional information from single trial responses not detected by amplitude evaluation. CONCLUSIONS: RQA allows quantifying signal characteristics of single trial ERPs measured with and without noise induced by parallel MRI. RQA power to discriminate responses to different tone types was similar to linear amplitude based analysis. SIGNIFICANCE: RQA has the potential to detect differences of signal features in response to a standard oddball paradigm and provide additional trial-by-trial information compared to classical amplitude based analysis. PMID- 22321296 TI - Widening the horizon of neonatal neurophysiology. PMID- 22321297 TI - Radial and tangential components of dipolar sources and their magnetic fields. PMID- 22321298 TI - Reconstruction of quasi-radial dipolar activity using three-component magnetic field measurements. AB - OBJECTIVE: While standard magnetoencephalographic systems record only one component of the biomagnetic field, novel vector-biomagnetometers enable measurement of all three components of the field at each sensing point. Because information content in standard one-component magnetoencephalography (MEG) is often not adequate to reconstruct quasi-radial dipolar activity, we tested the hypothesis that quasi-radial activity can be estimated using three-component MEG. METHODS: We stimulated the right median nerve in 11 healthy volunteers and recorded the somatosensory evoked fields over the contralateral hemisphere using a novel vector-biomagnetometer system comprised of SQUID-based magnetometer triplets. Source reconstruction for the early cortical components N20m and P25m was subsequently performed. RESULTS: Both tangential and quasi-radial dipolar activity could be reconstructed in 10 of the 11 participants. Dipole locations were found in the vicinity of the central sulcus, and dipole orientations were predominantly tangential for N20m and quasi-radial for P25m. The mean location difference between the tangential and quasi-radial dipoles was 11.9 mm and the mean orientation difference was 97.5 degrees . CONCLUSIONS: Quasi-radial dipolar activity can be reconstructed from three-component magnetoencephalographic measurements. SIGNIFICANCE: Three-component MEG provides higher information content than does standard MEG. PMID- 22321299 TI - Motor unit number index (MUNIX) versus motor unit number estimation (MUNE): a direct comparison in a longitudinal study of ALS patients. AB - OBJECTIVE: To evaluate how the motor unit number index (MUNIX) is related to high density motor unit number estimation (HD-MUNE) in healthy controls and patients with amyotrophic lateral sclerosis (ALS). METHODS: Both MUNIX and HD-MUNE were performed on the thenar muscles in 18 ALS patients and 24 healthy controls. Patients were measured at baseline, within 2 weeks, and after 4 and 8 months. Clinical evaluation included Medical Research Council (MRC) scale and the ALS functional rating scale (ALSFRS). RESULTS: There was a significant positive correlation between MUNE and MUNIX values in ALS patients (r=0.49 at baseline; r=0.56 at 4 months; r=0.56 at 8 months, all p<0.05), but not in healthy controls. After 8 months, both MUNE and MUNIX values of the ALS patients decreased significantly more compared to MRC scale, ALS functional rating scale (ALSFRS) and compound muscle action potential (CMAP) (p<0.05). There was no significant difference in relative decline of MUNIX and HD-MUNE values. CONCLUSIONS: In ALS patients, MUNIX and HD-MUNE are significantly correlated. MUNIX has an almost equivalent potential in detecting motor neuron loss compared to HD-MUNE. SIGNIFICANCE: MUNIX could serve as a reliable and sensitive marker for monitoring disease progression in ALS. PMID- 22321300 TI - Iron content (PIXE) in competent and incompetent veins is related to the vein wall morphology and tissue antioxidant enzymes. AB - Impaired venous drainage of the lower extremities determines a cascade of pathologic events leading to chronic venous disease (CVD). It is believed that the one cause of CVD is red blood cell extravasation and local iron overload that could generate free radicals and iron-dependent inflammation. The aim of this study was to investigate the relationship between: the intracellular iron deposits in varicose veins and tissue oxidative state measured by: the Proton Induced X-ray Emission Spectroscopy (Fe(PIXE)), (tSOD), (tGPx), (tTBARs) and (boxDNA). Patients with diagnosed CVD were qualified for surgical procedure. Entire trunk of the great saphenous vein (GSV) was extracted. Part located near medial ankle was considered competent (C) in duplex ultrasonography (USG) examination. The incompetent (I) part was extracted from GSV where USG showed incompetent valves and massive venous reflux. The difference between local tFe(PIXE), tTBARS, boxDNA, tGPx, tSOD in incompetent and competent part of vein tissue was statistically significant. Intima/media ratio directly correlated with Fe(PIXE) C/I concentration. Iron deposition in competent vs incompetent part of vein was also related to the oxidative stress parameters (boxDNA). The findings from this pilot study suggest that Fe(PIXE) measurement may be useful for explaining the progression of chronic venous disease. PMID- 22321301 TI - Acute kidney injury after placement of an antibiotic-impregnated cement spacer during revision total knee arthroplasty. AB - We performed a retrospective cohort study of 84 patients to determine the incidence and predictors of acute kidney injury after antibiotic-impregnated cement spacer (ACS) placement for infected total knee arthroplasties. Acute kidney injury was defined as a more than 50% rise in serum creatinine from a preoperative baseline to a level greater than 1.4 mg/dL within 90 days postoperatively. Total incidence was 17% (n = 14; 95% confidence interval [CI], 10%-26%), and acute kidney injury was significantly associated with ACS tobramycin dose as both a dichotomous variable (>4.8 g; odds ratio, 5.87; 95% CI, 1.43-24.19; P = .01) and linear variable (odds ratio, 1.24 for every 1-g increase; 95% CI, 1.00-1.52; P = .049). Routine monitoring of serum creatinine and measurement of serum aminoglycoside levels in response to a threshold creatinine rise may be warranted after the placement of an aminoglycoside containing ACS. PMID- 22321302 TI - CT afferents. PMID- 22321303 TI - Current biology. PMID- 22321304 TI - Replication timing: the early bird catches the worm. AB - Different replication origins in eukaryotes are activated at different times during S phase. New work indicates that the time at which an origin fires is related to its ability to recruit replication initiation factors that are limiting within the cell. PMID- 22321305 TI - Fungal biogeochemistry: a central role in the environmental fate of lead. AB - Fungi play major roles in biogeochemistry and are responsible for many metal transformations during mineral weathering. A recent finding that fungi transform lead to chloropyromorphite highlights the importance of fungi in biogeochemical processes. PMID- 22321306 TI - Social neuroscience: more friends, more problems...more gray matter? AB - The social brain hypothesis generically posits that increasing social group size relates is associated with an increase in neocortex size. A new study identifies, within a species, the specific neural circuit that may confer the primate ability to manage social relationships as they increase in number. PMID- 22321307 TI - Plant self-incompatibility: ancient system becomes a new tool. AB - Expressing a pollen self-incompatibility gene from Papaver rhoeas (poppy) in Arabidopsis thaliana renders the latter sensitive to an exquisitely precise induced cell death response. This simple system may have wide application in biotechnology and research. PMID- 22321308 TI - Calcium signaling: deciphering the calcium-NFAT pathway. AB - Rapid cellular calcium oscillations activate gene expression hours later. How this temporal response amplification is achieved has until now been largely a mystery. An elegant combination of experimental strategies and a model that encompasses non-linear inputs and outputs now sheds new light on this long standing problem. PMID- 22321309 TI - Cortical development: the sources of spontaneous patterned activity. AB - A recent study has found that spontaneous neural activity in the developing visual cortex has two distinct origins - local intracortical circuits and spontaneous activity in the retina. PMID- 22321310 TI - Face recognition: lessons from a wasp. AB - The golden paper wasp is a social insect whose colony members have the remarkable ability to recognise each others' faces. New research shows that this species is singularly skilled at learning about faces, opening interesting perspectives on convergent evolution of specialist cognitive abilities in insects and vertebrates. PMID- 22321311 TI - Endosperm imprinting: a child custody battle? AB - Endosperm gene imprinting has long been speculated to control nutrient allocation to seeds. For the first time, an imprinted gene directly involved in this process has been identified. PMID- 22321312 TI - Actin filaments as tension sensors. AB - The field of mechanobiology has witnessed an explosive growth over the past several years as interest has greatly increased in understanding how mechanical forces are transduced by cells and how cells migrate, adhere and generate traction. Actin, a highly abundant and anomalously conserved protein, plays a large role in forming the dynamic cytoskeleton that is so essential for cell form, motility and mechanosensitivity. While the actin filament (F-actin) has been viewed as dynamic in terms of polymerization and depolymerization, new results suggest that F-actin itself may function as a highly dynamic tension sensor. This property may help explain the unusual conservation of actin's sequence, as well as shed further light on actin's essential role in structures from sarcomeres to stress fibers. PMID- 22321313 TI - Sulphur isotope fractionation during the reduction of elemental sulphur and thiosulphate by Dethiosulfovibrio spp. AB - Stable sulphur isotope fractionation was investigated during reduction of thiosulphate and elemental sulphur at 28 degrees C by growing batch cultures of the sulphur- and thiosulphate-reducing bacteria Dethiosulfovibrio marinus (type strain DSM 12537) and Dethiosulfovibrio russensis (type strain DSM 12538), using citrate as carbon and energy source. The cell-specific thiosulphate reduction rate in the growth phase was 7.4+/-3.9 fmol cell(-1) d(-1). The hydrogen sulphide produced was enriched in (32)S by 10.3+/-1 0/00 compared with total thiosulphate sulphur, close to previous experimental results observed for other sulphate- and non-sulphate-reducing bacteria. Elemental sulphur reduction yields sulphur isotope enrichment factors between-1.3 and-5.2 0/00 for D. russensis and-1.7 and 5.1 0/00 for D. marinus. The smaller fractionation effects are observed in the exponential growth phase (cellular rates between 5 and 70 fmol S degrees cell( 1) d(-1)) and enhanced discrimination under conditions of citrate depletion and cell lysis (cellular rates between 0.3 and 3 fmol S degrees cell(-1) d(-1)). PMID- 22321314 TI - Ocean acidification reduces coral recruitment by disrupting intimate larval-algal settlement interactions. AB - Ecology Letters (2012) 15: 338-346 ABSTRACT: Successful recruitment in shallow reef ecosystems often involves specific cues that connect planktonic invertebrate larvae with particular crustose coralline algae (CCA) during settlement. While ocean acidification (OA) can reduce larval settlement and the abundance of CCA, the impact of OA on the interactions between planktonic larvae and their preferred settlement substrate are unknown. Here, we demonstrate that CO2 concentrations (800 and 1300 MUatm) predicted to occur by the end of this century significantly reduce coral (Acropora millepora) settlement and CCA cover by >= 45%. The CCA important for inducing coral settlement (Titanoderma spp., Hydrolithon spp.) were the most deleteriously affected by OA. Surprisingly, the only preferred settlement substrate (Titanoderma) in the experimental controls was avoided by coral larvae as pCO2 increased, and other substrata selected. Our results suggest OA may reduce coral population recovery by reducing coral settlement rates, disrupting larval settlement behaviour, and reducing the availability of the most desirable coralline algal species for successful coral recruitment. PMID- 22321315 TI - A national study of risk and protective factors for substance use among youth in the child welfare system. AB - While child welfare services are intended, in part, to diminish maltreatment's negative impact on adolescents' development, there is evidence that receiving child welfare services affects adolescents' substance use adversely. The literature on the extent and correlates of this problem is still emerging. The present study aims to fill part of this gap by examining the association between baseline psychosocial risk and protective factors on engagement in substance use behavior over a period of 36 months for child welfare involved youth. It further compares substance use behavior between youth placed in out-of-home care and those who remained with their biological families. Data come from the National Survey of Child and Adolescent Well-Being (NSCAW), a national probability study of children and adolescents undergoing investigation for abuse or neglect. The sample for this analysis was restricted to 827 youth who were 11 years or older at baseline data collection. Key findings include a high rate of social substance use (47.7%) and illicit substance use (17.4%). There was a limited role of protective factors in mitigating risk behavior for social substance use (caregiver connectedness; OR=0.51, p<0.05). Avoiding foster care placement was a protective factor for illicit substance use (OR=0.43, p<0.05). Delinquency was a risk factor associated with both social substance use (OR=1.06, p<0.01) and hard substance use (OR=1.10, p<0.001). Given the high prevalence of substance use among child welfare involved youth, prevention efforts for this population require a better understanding of biological, psychological, and social protective factors. The child welfare system is an untapped resource that has the potential to be a gateway to and a platform for substance abuse prevention services that should be incorporated into child welfare safety and permanency interventions. PMID- 22321316 TI - The role of therapeutic apheresis in high immunologic risk renal transplantation: a review of current trends. AB - Immunologic sensitization, defined by the presence of antibodies directed against donor human leukocyte antigen (or so called donor-specific antibodies [DSA]), is common among those awaiting kidney transplantation, and is associated with worse outcomes following transplant. Existing DSA have historically been screened for pretransplant using complement-dependent cytotoxic crossmatching and their risk circumnavigated through policies that prohibit transplants between incompatible donor-recipient pairs. This risk avoidance strategy maximizes outcomes following transplant, but at the expense of limiting access to transplant for sensitized individuals. Over the last decade, the field of kidney transplantation has moved to actively modify the risks posed by DSA, rather than to simply avoid them. More sensitive detection methods have provided detailed immunologic risk stratification of potential donor-recipient pairs. Desensitization protocols, in which therapeutic aphaeresis plays a central role, have been used to reduce the potential harms posed by DSA. More recently, desensitization and paired donor exchange programs have been used in combination to expand transplantation to highly sensitized patients with incompatible living donors. It is likely that this combination of risk mitigation and avoidance strategies will be used together more often to both maximize individuals' access to transplant, and optimize patient and graft outcomes. PMID- 22321317 TI - Vertical subsigmoid osteotomy fixation with miniplates: a case report. PMID- 22321318 TI - Metabolome analysis of photosynthesis and the related primary metabolites in the leaves of transgenic rice plants with increased or decreased Rubisco content. AB - Because the comprehensive effects on metabolism by genetic manipulation of leaf Rubisco content are unknown, metabolome analysis was carried out on transgenic rice plants with increased or decreased Rubisco content using the capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS) technique. In RBCS sense plants, an increase in Rubisco content did not improve light-saturated photosynthesis. Glyceraldehyde 3-phosphate and sedoheputulose 7-phosphate levels increased, but ribulose bisphosphate (RuBP), ATP and ADP levels were not affected. It is considered from these results that RuBP regeneration independent of ATP supply became a bottleneck for photosynthesis. In RBCS-antisense plants, a decline in Rubisco content decreased photosynthesis with a substantial accumulation of RuBP. ATP and ADP levels also increased and were associated with increases in the diphosphate and triphosphate compounds of other nucleosides. These results imply that a decline in Rubisco content slowed down the Calvin cycle and that the resultant excess energy of ATP was transferred to other nucleoside diphosphates and triphosphates. The levels of amino acids tended to decline in RBCS-sense plants and increase in RBCS-antisense plants, probably reflecting the demand for Rubisco synthesis. Starch and carbohydrate levels decreased only in RBCS-antisense plants. Thus, genetic manipulation of Rubisco contents widely affected C and N metabolism in rice. PMID- 22321319 TI - Positive diversifying selection on Plasmodium vivax RON2 protein. AB - Plasmodium rhoptry neck protein 2 (RON2), which is released from the neck portion of the merozoite rhoptries and interacts with the microneme protein Apical Membrane Antigen 1 (AMA1), plays a crucial role in erythrocyte invasion. In this study, we sequenced the Plasmodium vivax RON2 gene from 19 P. vivax isolates collected in central China in order to establish whether this protein is under positive diversifying selection, which may occur as a result of protective host immune pressure?. In comparison with the P. vivax Sal-1 reference line, we found 10 amino acid substitutions dispersed throughout the open reading frame as well as indels caused by polymorphism in a repeat unit (21-23 repeats of (Q/E/K/N/H)(G/D)G(H/L/Y/P)G) in the second tandem repeat region located at amino acid positions 541-650. A McDonald-Kreitman test with RON2 sequences from the primate malaria parasite Plasmodium knowlesi, detected significant departure from neutrality in the PvRON2 3' region (nucleotide positions 2668-6609). These results suggest that the PvRON2 gene has evolved under positive diversifying selection. PMID- 22321320 TI - [The advancement of analgesia and sedation: from improving comfortability to protection of organ dysfunction in critically ill patients]. PMID- 22321321 TI - [A randomized, double blind, placebo-controlled, parallel and multicenter study to evaluate the safety and efficacy of pioglitazone with sulphonylurea in type 2 diabetic patients]. AB - OBJECTIVE: To evaluate the safety and efficacy of 30 mg pioglitazone hydrochloride combined with sulphonylurea in the treatment of type 2 diabetic patients. METHODS: A randomized, double blind, placebo-controlled, parallel group, multicenter study was performed. A total of 236 patients, who had fasting plasma glucose (FPG) 7.5 - 13.0 mmol/L and glycosylated hemoglobin A1c (HbA1c) 7.0% - 12.0%, treated with stable dosage of a sulphonylurea for at least 30 days previously, were randomized to receive placebo or pioglitazone 30 mg once daily for 16 weeks. The sulphonylurea and dosage remained unchanged. RESULTS: The patients who had been treated with pioglitazone 30 mg showed significant decrease than that in the placebo group on the average from baseline in FPG [(1.48 +/- 2.08) mmol/L vs (-0.17 +/- 1.92) mmol/L, P < 0.05], and in HbA1c [(0.92 +/- 0.10)% vs (0.28 +/- 0.11)%, P < 0.05]. Since fasting plasma insulin (FIns) levels decreased (0.24 +/- 0.04) mU/L and (0.09 +/- 0.04) mU/L in the two groups. The homeostatic model assessment insulin resistant (HOMA-IR) decreased 1.42 +/- 2.90 and 0.46 +/- 3.53 in two groups. The triglyceride level was decreased 0.36 mmol/L and 0.14 mmol/L, and the HDL-C level increased 0.17 mmol/L and 0.05 mmol/L in two groups. There were significant differences in two groups (all P < 0.05). CONCLUSIONS: The 16-week clinical study demonstrated that pioglitazone hydrochloride with a dosage of 30mg daily, could significantly improve the blood glucose control and enhance the insulin sensitivity, lower triglyceride and raise HDL-C level as an additional therapy to a stable-dose sulphonylurea in Chinese type 2 diabetic patients previously poorly controlled by single sulphonylurea therapy, and furthermore had good safety and compliance. PMID- 22321322 TI - [Radial augmentation index is associated with cardiovascular risk and arterial stiffness]. AB - OBJECTIVE: To investigate whether radial augmentation index (AI) associates with cardiovascular risk as well as arterial stiffness. METHODS: A total of 4985 subjects, 2417 men and 2568 women, aged 18 - 96 (50.9 +/- 14.7) years, were recruited. AI was measured in the left radial artery using tonometry Colin HEM 9000AI. Carotid-femoral PWV (CFPWV) and carotid-radial PWV (CRPWV) were examined by automatic pulse wave velocity (PWV) measuring system. Framingham risk score and Chinese ischemic cardiovascular disease risk score were applied upon subjects without cardiovascular disease to calculate individual cardiovascular risk respectively. RESULTS: Radial AI (rAI) was significantly higher in women than in men[ (83.18 +/- 12.36)% vs (71.93 +/- 15.22)%, P < 0.01]. Simple correlation analysis showed rAI was significantly correlated to two cardiovascular risk scores or CFPWV and CRPWV. After adjusted for multi-factors, rAI was still significantly correlated to Framingham risk score or Chinese ischemic cardiovascular disease risk score (r = 0.17 and 0.12) in men respectively (P < 0.05), while r were 0.09 and 0.08 in women respectively (P < 0.05). In multivariate analysis, there was a significant association between CFPWV and rAI (r = 0.14 in men, r = 0.10 in women, P < 0.01), whereas the relation ship between CRPWV and rAI was not found. The relationship between rAI and cardiovascular risk or PWV became weaker for those aged above 50 years. CONCLUSION: Augmentation index might be a useful marker of cardiovascular risk and arterial stiffness, which could be more feasible for younger subjects as a tool for risk differentiation. PMID- 22321323 TI - [C-reactive protein and non-valvula atrial fibrillation combining with thrombosis]. AB - OBJECTIVE: To investigate the alteration of plasma C-reactive protein(CRP) count in patients with non-valvula atrial fibrillation combining thrombosis. METHODS: A total of 154 patients with non-valvula atrial fibrillation were divided into thrombus group (n = 46) and non-thrombus group (n = 108) in accordance with transesophageal echocardiography (TEE) results. The concentration of CRP by scattering turbidimetry, D-dimer by immunoturbidmetry, left atrium diameter (LAd), fraction shortening (FS) and left ventricular ejection fraction (LVEF) by TEE or echocardiography were detected. Logistic multi-factors regression analysis was performed. RESULTS: There were significant differences in CRP [(5.77 +/- 6.37) mg/L vs (1.73 +/- 2.39) mg/L, P = 0.003], LAd [(59.86 +/- 10.70) mm vs (47.97 +/- 13.19) mm, P < 0.001] and LVEF [(58.75 +/- 8.28)% vs (64.10 +/- 6.75)%, P < 0.001] between thrombus group and non-thrombus group. The results of logistic regression analysis found CRP >= 1.33 mg/L (OR 2.856, 95%CI 1.235 - 6.600, P = 0.014) and LAd >= 54.5 mm (OR 4.236, 95%CI 1.877 - 9.562, P = 0.001) were independent risk factors of patients with non-valvula atrial fibrillation combining with thrombosis. CONCLUSIONS: CRP and LAd are independent risk factors for patients with non-valvula atrial fibrillation combining with thrombosis. Inflammation may involve with the formation of thrombosis. PMID- 22321324 TI - [The clinical characteristics of intra-acinar pulmonary artery inflammation and its effect on clinical parameters in smokers with normal lung function and patients with chronic obstructive pulmonary disease]. AB - OBJECTIVE: To study the pathological characteristics of intra-acinar pulmonary artery inflammation and its correlation with smoking index and disease progression in smokers with normal lung function and smokers with chronic obstructive pulmonary disease (COPD). METHODS: Patients requiring lung resection for peripheral lung cancer were divided into group A (nonsmokers with normal lung function, n = 10), group B (smokers with normal lung function, n = 13), and group C (smokers with stable COPD, n = 10). The lung tissue far away from tumor were resected to compare the pathological changes of intra-acinar pulmonary arteries and infiltration level of inflammatory cell in pulmonary non-muscularized arteries (NMA), pulmonary partially muscularized arteries (PMA) and muscularized arteries (MA) among the three groups. The correlation analysis was made among infiltration level, smoking index, percentage of predicted value of forced expiratory volume in one second (FEV(1)%Pred), six-minute-walk distance (6MWD) and BODE index. RESULTS: (1) Both group B and group C showed the intima and media thickness of MA was significantly higher, the lumen area of MA was narrower and the proportion of MA was higher, and collagenous fiber of MA adventitial proliferated and area increased in group C (P < 0.05 or P < 0.01). (2) In group B and group C, the percentage of the intra-acinar pulmonary arteries that contained leukocytes, T lymphocytes, CD(8)(+)T lymphocytes and the number of these positive cells infiltrating the intra-acinar pulmonary arteries were increased, especially an increased number of CD(8)(+)T lymphocytes infiltrating in the arterial adventitia as compared with group A, moreover there were significant difference between group C and group B (P < 0.05 or P < 0.01). In group B and group C, the degree of these positive cells infiltrating NMA, PMA and MA presented a decreasing sequence (P < 0.05 or P < 0.01). Among the intima, media and adventitia of MA, the infiltration of these positive cells was the highest in the adventitia. Among group A, group B and group C, infiltration degree of CD(4)(+)T lymphocyte, B lymphocyte, macrophage and neutrophil demonstrated no significant difference, also among NMA, PMA and MA (P > 0.05). (3) The number of leukocytes, T lymphocytes, CD(8)(+)T lymphocytes infiltrating MA showed a positive correlation with the thickness of MA (r = 0.563, 0.627, 0.589, P < 0.01, respectively) and smoking index (r = 0.551, 0.665, 0.600, P < 0.01, respectively), moreover the degree of these cells infiltrating MA demonstrated negative correlation with FEV(1)%Pred (r = -0.763, -0.703, -0.767, P < 0.01, respectively). Also infiltrating degree of T lymphocytes and CD(8)(+)T lymphocytes was positively correlated with BODE (r = 0.390, 0.476, P < 0.05, respectively). Furthermore the infiltrating degree of CD(8)(+)T lymphocytes had negative correlation with 6MWD (r = -0.356, P < 0.05). CONCLUSIONS: (1) Pulmonary arterial inflammation appears in smokers with normal lung function and smokers with COPD patients. It involves in all types of intra-acinar pulmonary arteries especially NMA and infiltrates whole layer of MA with a characteristic of CD(8)(+)T lymphocytes infiltrating in the adventitia of intra-acinar pulmonary arteries. (2) Pulmonary inflammation is closely correlated to cigarette smoking and clinical parameters such as BODE index, FEV(1)% pred and 6MWD. It is one of the key factors affecting the progression of COPD. PMID- 22321325 TI - [The effects of two health education models on psychological and nutritional profile of patients waiting for kidney transplantation]. AB - OBJECTIVE: To investigate the effects of two health education models on the psychology and nutrition of patients waiting for cadaveric renal transplantation. METHODS: A total of 125 patients waiting for cadaveric renal transplantations were involved in our study. They were diagnosed with chronic renal failure in our hospital during September 1, 2009 to August 30, 2010. The patients were randomly divided into control group (n = 62) and observational group (n = 63). Patients in the control group received traditional health education with routine preoperative education during hospitalization. In the observational group, full-time nurses assessed the nutrition status of each patient and monitored the data. The observational patients were followed up and were given dietary guidance and knowledge of transplantation. Various kinds of education formats were adopted in observational group to provide communication opportunities between patients and surgeons in charge as well as patients who underwent transplantation. Psychological testings of patients in both groups were tested by self-rating anxiety scale (SAS) and self-rating depression scale (SDS) before and after the health education. Triceps skinfold thickness (TSF), mid-arm muscle circumference (MAMC) and biochemistry index were also tested. Psychological and nutritional status of patients in the two groups was compared. RESULTS: There were no significant differences in scores of the SAS, SDS, TSF, Hb, and albumin (Alb) between the two groups (all P > 0.05) before health education. After health education, SAS and SDS in observational group were lower than those in the control group (40.02 +/- 9.05 vs 47.05 +/- 10.32, 42.70 +/- 10.01 vs 50.83 +/- 10.12; both P < 0.01). Both TSF and Hb were elevated after education (P < 0.001 or 0.05). Alb was significantly elevated in the observational group [(35.67 +/- 6.19) g/L vs (37.48 +/- 5.09) g/L, P < 0.01]. CONCLUSION: Comprehensive and various health education methods can significantly alleviate mental stress and improve nutrition of the patients waiting for kidney transplantation, which is helpful for patients facing disease positively and having a better quality of life. PMID- 22321326 TI - [Comparison of three anti-aquaporin 4 antibody detection methods in neuromyelitis optical]. AB - OBJECTIVE: To evaluate three methods of detecting anti-aquaporin 4(AQP4) antibody in neuromyelitis optical(NMO), including indirect immunofluorescence assay organization (IIF), cell immunofluorescence method (CBA) and ELISA. METHODS: The patients were divided into NMO group (n = 29), multiple sclerosis (MS) group (n = 23), and healthy controls group (n = 50). IIF, CBA and ELISA were used in 3 groups to detect serum anti-AQP4 antibody. The sensitivity and specificity as well as the consistency of positive results were compared. RESULTS: In the aspect of the sensitivity of the three anti-AQP4 antibody to diagnosis NMO, CBA (72.4%) > IIF (62.1%) > ELISA (51.7%); in the aspect of specificity, CBA (100.0%) > ELISA (98.6%) > IIF (97.3%). Kappa testing and evaluation method showed that the three detection methods were all in good consistency, particular in CBA and ELISA (P < 0.01). CONCLUSIONS: CBA method showed a highest specificity and sensitivity in all these three anti-AQP4 antibody detection methods. CBA and ELISA are in better consistency of positive results. PMID- 22321327 TI - [The correlation between NPHS2 polymorphism and IgA nephropathy in northern Chinese patients]. AB - OBJECTIVE: To examine the polymorphism in NPHS2 gene of IgA nephropathy in northern Chinese patients and to investigate the possible association of the NPHS2 polymorphism with the development of IgA nephropathy, as well as its clinical and histologic manifestations. METHODS: The polymorphism of NPHS2 was analyzed by direct DNA sequencing in 32 northern Chinese patients with IgA nephropathy (16 with heavy proteinuria and 16 with isolated hematuria). According to preliminary results, a total of 537 IgA nephropathy patients were genotyped for the NPHS2 C357T polymorphism by PCR combined with restriction fragment length polymorphism (PCR-RFLP). We collected clinical and histologic manifestations for gene analysis in patients with IgA nephropathy, such as age, sex, urine protein excretion and so on. RESULTS: Eight NPHS2 polymorphisms (-931A > T, -601C > T, 19G > T, 171A > G, 357C > T, IVS3-21C > T, 1023C > T and 1107A > G) were identified. The preliminary results of gene sequencing showed that the frequency of 357T allele in nephrotic syndrome group was obviously lower than isolated hematuria group (0.038 vs 0.125, P < 0.05). In 537 IgA nephropathy patients with clinical and histologic data, the average urinary protein excretion in the patients with the 357CT/TT genotype was less (P = 0.023). The incidence of urinary protein of more than 3.5 g/d was significantly lower in patients with T allele and TT/CT genotype, respectively (P = 0.017 and 0.011). The logistic regression analysis indicated that, even after adjusting for the effect of hypertension and age of patients, the CT/TT genotype of NPHS2 C357T was an independent protective factor for the urinary protein excretion more than 3.5 g/d (P = 0.012, OR = 0.485, 95%CI 0.275 - 0.84). CONCLUSIONS: Eight NPHS2 polymorphisms were identified in northern Chinese IgA nephropathy patients. The frequencies of NPHS2 T allele and TT/CT genotype were the protective factors for urinary protein, especially with that of more than 3.5 g/d. PMID- 22321328 TI - [Association between HLA-Cw polymorphism and inflammatory bowel disease]. AB - OBJECTIVE: To investigate the association of HLA-Cw alleles with inflammatory bowel disease(IBD), so as to identify IBD susceptibility gene. METHODS: The HLA Cw genotype were analyzed in 100 patients with ulcerative colitis (UC), 73 patients with Crohn's disease (CD) and 106 randomly ethnically matched healthy controls by sequence specific primer polymerase chain (PCR-SSP). RESULTS: HLA Cw*07 gene phenotype frequencies increased in patients with UC (0.430) compared with that in healthy controls (0.226), P = 0.002; while HLA-Cw*12 gene phenotype frequencies increased in patients with CD (0.356) compared with that in healthy controls (0.123), P = 0.000. CONCLUSION: HLA-Cw*07 allele and HLA-Cw*12 allele may be strongly associated with the susceptibility of UC and CD, respectively. PMID- 22321329 TI - [The relationship between polymorphism of genes XPA, XPC, XPD, XRCC1 and susceptibility to acute lymphoblastic leukemia]. AB - OBJECTIVE: To study the relationship between polymorphism of genes XPA, XPC, XPD, XRCC1 and susceptibility to acute lymphoblastic leukemia (ALL) in a Chinese population. METHODS: Polymorphism were determined by a case-control study through matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry method of Mass-ASSAY platform in 114 confirmed ALL cases and 169 age and sex-matched controls, so as to compare the relationship between different genotypes and ALL risk. RESULTS: Multivariate logistic regression analysis revealed that individuals carrying at least one 23G variant allele (AG/GG genotypes) had a significantly increased risk for ALL (adjusted OR 2.02; 95%CI 1.08 - 3.78) compared with the wild-type genotype (23AA), and evidence that positive interactions between the polymorphisms in XPC C499T and XPA A23G might occur. Furthermore, individuals with both putative risk genotypes had a significantly higher risk (adjusted OR 5.60; 95%CI 1.57 - 19.90), compared with those with both wild-genotypes. By contrast, no significant association was observed between the XPD T751G, XRCC1 G399A, C194T polymorphism and ALL risk. CONCLUSIONS: XPA A23G and XPC C499T polymorphism may contribute to the risk of developing ALL. There are significant combinations between XPC C499T and XPA A23G. PMID- 22321330 TI - [The protective effects of bifidobacterial adhesin on ischemic reperfusion injury of intestine in rats]. AB - OBJECTIVE: To investigate the protection effect of bifidobacterial adhesin for intestine ischemia/reperfusion (I/R) injury on gut barrier function in rat. METHODS: Seventy-two male SD rats were randomly divided into sham operation group (n = 24), I/R model group (n = 24) and pretreatment group of bifidobacterial adhesin (pretreatment group, n = 24). Six rats were anatomized at 6 h, 1 d, 4 d and 7d after inducing I/R model in each group, respectively. The pathological changes of the terminal ilea and the blood levels of TNFalpha, IL-6, IL-10, diamine oxidase (DAO), and the activity and content of D-lactic acid were observed. RESULTS: The blood levels of TNFalpha, IL-6, DAO and D-lactic acid in I/R model group were significantly higher than sham operation group at all time points (P < 0.05), while the blood level of IL-10 was no significantly change. The activity of IL-6 and DAO in pretreatment group was significantly lower than I/R model group at all time points (P < 0.05), the blood level of TNFalpha in pretreatment group was significantly lower than I/R model group at 1 d, the blood level of D-lactic was significantly lower than I/R model group at 4 d and 7 d (P < 0.05). Intestinal pathological damages were obviously milder in pretreatment group than I/R model group at all time points (Chiu's pathological scores: 6 h, 3.22 +/- 0.22 vs 3.57 +/- 0.20; 1 d, 3.77 +/- 0.13 vs 3.90 +/- 0.12; 4 d, 2.93 +/ 0.23 vs 3.07 +/- 0.21; 7 d, 2.10 +/- 0.30 vs 2.22 +/- 0.17, all P < 0.05). CONCLUSION: The pretreatment of bifidobacterial adhesin could protect the intestinal mucosa from I/R injury, and alleviate intestinal ischemic reperfusion injury. PMID- 22321331 TI - [The expression of the type I interferon system in muscle and lung of autoimmune myositis rat model]. AB - OBJECTIVE: To investigate the expression levels of the type I IFN system in muscle and lung of experimental autoimmune myositis (EAM) model and to evaluate whether the type I IFN system associates with the pathogenesis of the EAM model in rats. METHODS: The EAM model was established to determine creatine kinase (CK) in blood serum. The pathology of muscle and lung tissue was examined by hematoxylin-eosin staining. The concentration of type I IFN system mRNA in muscle and lung tissue was detected by real-time PCR. RESULTS: The concentration of CK in model group [(209.17 +/- 91.95) IU/L] was significantly higher than that of two control groups (P < 0.05). The scores of muscle and lung in EAM model were significantly higher than that of control groups (all P < 0.05). The expression levels of the type I IFN system in muscle of EAM model were significantly higher than that of control groups (all P < 0.05). The expression levels of the type I IFN system in muscle with EAM model were positively correlated with CK and the scores of muscle (all P < 0.05). The expression levels of IFNalpha, IFNbeta, IFNalphaR1, signal transducer and activator of transcription 1 (STAT1), myxovirus resistance protein 1 (MX1) in lung of EAM model were significantly higher than those of control groups (P < 0.05), but not seen in INF-induced protein with tetratricopeptide repeats 1 (IFIT1) and IFN-stimulated gene 15 (ISG15). The expression levels of IFNalpha, IFNbeta, IFNalphaR1, STAT1 and MX1 in lung with EAM model were positively correlated with the scores of lung pathology (all P < 0.05). CONCLUSION: The type I IFN system probably played a crucial role in the pathogenesis and the pathology of muscle and lung of EAM model. PMID- 22321332 TI - [The relationship between oxidative injury induced by low glucose and mitochondrial membrane potential in HUVEC-12 cells]. AB - OBJECTIVE: To investigate the relationship between the oxidative injury induced by low glucose and mitochondrial membrane potential in HUVEC-12 cells. METHODS: Human umbilical vein endothelial cells HUVEC-12 were cultured in low concentration glucose for 4 h. Cell viability of HUVEC-12 cell was assessed with MTT assay. Dihydroethidium (DHE) was used as a reactive oxygen species (ROS) capture, which was detected the mean fluorescence intensity of samples and Rhodamine 123 as a fluorescence detector was to measure the level of mitochondrial membrane potential (MMP) in cells. RESULTS: Comparing to HUVEC-12 cells viability in 5.5 mmol/L glucose group (96.80 +/- 3.20)%, cells exposed to 2.8 mmol/L glucose group (66.40 +/- 1.60)% and 0 mmol/L glucose group (58.93 +/- 1.67)% were decreased by 32% and 40% respectively (P < 0.01). ROS level of 5.5 mmol/L glucose group, 2.8 mmol/L glucose group and 0 mmol/L glucose group were 0.59 +/- 0.02, 0.74 +/- 0.04 and 0.88 +/- 0.05, respectively, increased by 25% in cells exposed to 2.8 mmol/L glucose and by 48% in cells without glucose exposure comparing to 5.5 mmol/L glucose group (P < 0.01); MMP levels of 5.5 mmol/L glucose group, 2.8 mmol/L glucose group and 0 mmol/L glucose group were 148.83 +/ 3.51, 271.07 +/- 19.54 and 357.74 +/- 51.32 respectively, increased to 1.8 times in cells exposed to 2.8 mmol/L glucose and to 2.4 times in cells without glucose exposure comparing to 5.5 mmol/L glucose group (P < 0.01). CONCLUSION: Low glucose leads to injury in HUVEC-12 cells, which is probably induced by the oxidative stress via the increasing MMP. PMID- 22321333 TI - Five-Factor Model personality disorder prototypes: a review of their development, validity, and comparison to alternative approaches. AB - In this article, the development of Five-Factor Model (FFM) personality disorder (PD) prototypes for the assessment of DSM-IV PDs are reviewed, as well as subsequent procedures for scoring individuals' FFM data with regard to these PD prototypes, including similarity scores and simple additive counts that are based on a quantitative prototype matching methodology. Both techniques, which result in very strongly correlated scores, demonstrate convergent and discriminant validity, and provide clinically useful information with regard to various forms of functioning. The techniques described here for use with FFM data are quite different from the prototype matching methods used elsewhere. PMID- 22321334 TI - Levetiracetam as alternative stage two antiepileptic drug in status epilepticus: a systematic review. AB - BACKGROUND: The role of new antiepileptic drugs (AED) in the treatment of status epilepticus (SE) is of interest, especially in benzodiazepine-resistant status epilepticus where phenytoin is deemed inappropriate due to allergy or comorbidity. Levetiracetam (LEV) is a new AED with few side effects. It is easy to administer. Reports exist of its use in SE in adults. AIMS: To clarify the evidence for use of LEV as an alternative stage two AED in treatment of SE by a systematic review of the literature. METHOD: An online MEDLINE search identified 118 articles. The abstracts were screened for studies written in English, in which (1) at least two adults had been treated, and (2) LEV had been administered intravenously as the first AED, on its own or together with benzodiazepines. Ten studies were included. RESULTS: Out of the ten studies, seven were retrospective observational, two prospective observational, and one prospective randomized. The studies described a total of 334 patients. The most common reason for administrating LEV was that standard treatment was deemed inappropriate. The efficacy ranged from 44% to 94%, with higher efficacy reported in the retrospective studies. CONCLUSIONS: The evidence for use of LEV as an alternative stage two AED in SE is limited. The higher efficacy reported in retrospective studies indicates possible publication bias, and caution is advised when the results of these retrospective studies are considered in clinical decision making. PMID- 22321335 TI - Risk of mortality among patients with epilepsy in southern Taiwan. AB - OBJECTIVE: Previous studies suggested a higher risk of all-cause mortality in patients with epilepsy than in the general population. However, information on the age- and sex-specific risk of mortality, as well as on the cause-specific risk of mortality has been sparse. This study aims to determine sex-, age-, and cause-specific risk of mortality among patients with epilepsy from southern Taiwan. METHODS: A total of 2180 patients treated in a tertiary hospital in southern Taiwan between 1989 and 2008 were compared to the general population of Taiwan for age-, sex- and cause-specific mortalities. The age-, sex-, and calendar year-standardized mortality ratios (SMRs) were calculated to estimate the relative risks of mortality associated with the epilepsy. RESULTS: There are 266 (12.2%) deaths noted in the study period. The patients with epilepsy experienced a significantly increased SMR of all-cause mortality (SMR, 2.5; 95% confidence interval (CI), 2.2-2.8). The most significantly elevated age-specific SMR was 51.8 (95% CI, 6.2-187.2) and 8.6 (95% CI, 4.4-14.9) for male patients aged 0-9 years and female patients aged 20-29 years, respectively. Additionally, the most increased cause-specific SMR was noted for brain tumor (SMR, 21.4; 95% CI, 9.23-23.1), followed by accidental drowning (SMR, 8.8; 95% CI, 3.5-9.6) and falls (SMR, 5.7; 95% CI, 2.2-6.1). CONCLUSION: Younger epilepsy should be the object of aggressive treatments. Advancement in treating brain tumors and prevention of accidental injuries may help improve the survival of patients with epilepsy. PMID- 22321336 TI - Malaria transmission in Libreville: results of a one year survey. AB - BACKGROUND: In Gabon, vector transmission has been poorly studied. Since the implementation of the Roll Back malaria recommendations, clinical studies have shown a decline in the burden of malaria in Libreville, the capital city of Gabon. To better understand the transmission dynamic in Libreville, an entomological survey was conducted in five districts of the city. METHODS: Mosquitoes were sampled by human landing collection during 1 year in five districts of Libreville: Alibandeng, Beausejour, Camp des Boys and Sotega. Mosquitoes were identified morphologically and by molecular methods. The Plasmodium falciparum circumsporozoite indices were measured by ELISA, and the entomological inoculation rates (EIR) were calculated for all areas. Molecular assessments of pyrethroid knock down resistance (kdr) and of insensitive acetylcholinesterase resistance were conducted. RESULTS: A total of 57,531 mosquitoes were caught during 341 person-nights (161 person-nights indoor and 180 person-nights outdoor) among which, 4,223 were Anopheles gambiae s.l. The average Human Biting Rate fell from 15.5 bites per person during the rainy season to 4.7 during the dry season. The An. gambiae complex population was composed of An. gambiae s.s molecular form S (99.5%), Anopheles melas (0.3%) and An. gambiae s.s. form M (0.2%). Thirty-three out of 4,223 An. gambiae s.l. were found to be infected by P. falciparum (CSP index = 0.78%). The annual EIR was estimated at 33.9 infected bites per person per year ranging from 13 in Alibandeng to 88 in Sotega. No insensitive AChE mutation was identified but both kdr-w and kdr-e mutations were present in An. gambiae molecular form S with a higher frequency of the kdr-w allele (76%) than the kdr-e allele (23.5%). CONCLUSION: Malaria transmission in Libreville occurred mainly during the rainy season but also during the dry season in the five districts. Transmission level is high and seems to be very heterogeneous in the town. Interestingly, the highest EIR was recorded in the most central and urbanized quarter and the lowest in a peripheral area. The decrease of transmission usually seen from peri-urban areas to urban centers is probably more dependent of the socio-economic level of a quarter than of its location in the city. Urban malaria control programmes need to consider the socio economic level of an area rather than the location in the city in order to determine the areas most favourable to malaria transmission. PMID- 22321337 TI - Synthesis and reactivity of an isolable cobalt(I) complex containing a beta diketiminate-based acyclic tetradentate ligand. AB - A model for cobalamin was synthesized using a new monoanionic tetradentate nitrogen donor ligand; 2-(4-tolyl)-1,3-bis(2-isopropylpyridyl)propenediimine (Tol BDI((2-pp)2)H) (1), which utilizes isopropylpyridines as pendant arms on a beta diketiminate (BDI) backbone. During the synthesis of 1, the rearrangement product, Tol-BDI((2-pp)(4-pp))H (2) was observed. Metalation of 1 with zinc iodide and cobalt chloride yielded the corresponding Tol-BDI((2-pp)2)ZnI (3) and Tol-BDI((2-pp)2)CoCl (4) complexes. The redox properties of 4 in comparison to cobalamin were examined through electrochemical studies. Electrochemical and bulk reduction of complex 4 gave a diamagnetic cobalt(I) complex, Tol-BDI((2-pp)2)Co (5). Reactivity of 5 toward C-X bonds was investigated using methyl iodide and 1 iodo-2-(trimethylsilyl)acetylene, yielding Tol-BDI((2-pp)2)Co(CH(3))I and Tol BDI((2-pp)2)Co(C(2)Si(CH(3))(3))I respectively. Synthesis and characterization details for these complexes, including the crystal structure of 3, are reported. PMID- 22321338 TI - Blood donors' helping behavior is driven by warm glow: more evidence for the blood donor benevolence hypothesis. AB - BACKGROUND: The benevolence hypothesis (both donor and recipient gain) suggests that blood donors, compared to non-blood donors have a general altruistic motivational preference based on warm glow (i.e., "I donate because it makes me feel good"). With objective behavioral economics tests of altruism and warm-glow giving, this paper offers the first direct experimental test of this hypothesis. The prediction that blood donors will be motivated in general by warm glow was compared to predictions from other theoretical models: strong reciprocity and empathy. STUDY DESIGN AND METHODS: Four experiments and one prospective study examined blood donors' and nondonors' motivations for general charitable giving and blood donation. Variants of the dictator game (DG; a charity DG [CDG] and a warm-glow version of a CDG) were used to provide objective measures of altruism. RESULTS: Blood donors gave less than nondonors on the CDG, but gave more on the warm-glow version. Blood donors' actual donations (in the CDGs and blood donation) were associated with feelings of warm glow. There was no evidence that blood donors were motivated by strong reciprocity or empathic concerns. CONCLUSIONS: This paper offers objective behavioral evidence that blood donors' charitable giving and blood donation, compared to non-blood donors, is more strongly motivated by warm glow. This provides additional support for the benevolence hypothesis of blood donation. PMID- 22321339 TI - Functional, cognitive and psychological outcomes, and recurrent vascular events in Pakistani stroke survivors: a cross sectional study. AB - BACKGROUND: There is little direct data describing the outcomes and recurrent vascular morbidity and mortality of stroke survivors from low and middle income countries like Pakistan. This study describes functional, cognitive and vascular morbidity and mortality of Pakistani stroke survivors discharged from a dedicated stroke center within a nonprofit tertiary care hospital based in a multiethnic city with a population of more than 20 million. METHODS: Patients with stroke, aged > 18 years, discharged alive from a tertiary care centre were contacted via telephone and a cross sectional study was conducted. All the discharges were contacted. Patients or their legal surrogate were interviewed regarding functional, cognitive and psychological outcomes and recurrent vascular events using standardized, pretested and translated scales. A verbal autopsy was carried out for patients who had died after discharge. Stroke subtype and risk factors data was collected from the medical records. Subdural hemorrhages, traumatic ICH, subarachnoid hemorrhage, iatrogenic stroke within hospital and all other diagnoses that presented like stroke but were subsequently found not to have stroke were also excluded. Composites were created for functional outcome variable and depression. Data were analyzed using logistic regression. RESULTS: 309 subjects were interviewed at a median of 5.5 months post discharge. 12.3% of the patients had died, mostly from recurrent vascular events or stroke complications. Poor functional outcome defined as Modified Rankin Score (mRS) of > 2 and a Barthel Index (BI) score of < 90 was seen in 51%. Older age (Adj-OR 2.1, p = 0.01), moderate to severe dementia (Adj-OR-19.1, p < 0.001), Diabetes (Adj-OR-2.1, p = 0.02) and multiple post stroke complications (Adj-OR-3.6, p = 0.02) were independent predictors of poor functional outcome. Cognitive outcomes were poor in 42% and predictors of moderate to severe dementia were depression (Adj-OR-6.86, p < 0.001), multiple post stroke complications (Adj-OR-4.58, p = 0.01), presence of bed sores (Adj-OR-17.13, p = 0.01) and history of atrial fibrillation (Adj-OR-5.12, p < 0.001). CONCLUSIONS: Pakistani stroke survivors have poor outcomes in the community, mostly from preventable complications. Despite advanced disability, the principal caretakers were family rarely supported by health care personnel, highlighting the need to develop robust home care support for caregivers in these challenging resource poor settings. PMID- 22321340 TI - Microsatellite resources for Passeridae species: a predicted microsatellite map of the house sparrow Passer domesticus. AB - We identified microsatellite sequences of potential utility in the house sparrow (Passer domesticus) and assigned their predicted genome locations. These sequences included newly isolated house sparrow loci, which we fully characterized. Many of the newly isolated loci were polymorphic in two other species of Passeridae: Berthelot's pipit Anthus berthelotii and zebra finch Taeniopygia guttata. In total, we identified 179 microsatellite markers that were either isolated directly from, or are of known utility in, the house sparrow. Sixty-seven of these markers were designed from unique sequences that we isolated from a house sparrow genomic library. These new markers were combined with 36 house sparrow markers isolated by other studies and 76 markers isolated from other passerine species but known to be polymorphic in the house sparrow. We utilized sequence homology to assign chromosomal locations for these loci in the assembled zebra finch genome. One hundred and thirty-four loci were assigned to 25 different autosomes and eight loci to the Z chromosome. Examination of the genotypes of known-sex house sparrows for 37 of the new loci revealed a W-linked locus and an additional Z-linked locus. Locus PdoMU2, previously reported as autosomal, was found to be Z-linked. These loci enable the creation of powerful and cost-effective house sparrow multiplex primer sets for population and parentage studies. They can be used to create a house sparrow linkage map and will aid the identification of quantitative trait loci in passerine species. PMID- 22321341 TI - Upstaging of urothelial cancer at the time of radical cystectomy: factors associated with upstaging and its effect on outcome. AB - What's known on the subject? and What does the study add? The reported discordance between staging on transurethral bladder resection and on radical cystectomy pathology in the literature ranges from 20 to 80%.Correct staging in bladder cancer has direct implications for its management. The upstaging from organ-confined (OC) to non-organ-confined (nOC) disease has been reported in 40% of cases. Lymphovascular invasion (LVI) is a factor known to be associated with poor clinical outcome. Pathological upstaging was observed in our cohort in 40% of cases and most cases (80%) were upstaged from OC to nOC disease. During the study period the frequency of upstaging observed increased. We found LVI (hazard ratio [HR]= 5.07, 95% CI = 3.0-8.3, P < 0.001) and any histological variant variant (HR = 2.77, 95% CI = 1.6-4.8, P < 0.001) to be strong independent predictors of upstaging. Patients with clinical T2 bladder cancer found with upstaging at the time of radical cystectomy had a poorer outcome than patients with no upstaging. Identification of patients at high risk of upstaging at radical cystectomy is key to improving their management and outcome. OBJECTIVES: To analyse the details of bladder cancer (BC) staging in a large combined radical cystectomy (RC) database from two academic centres. To study rate and time trends, as well as risk factors for upstaging, especially clinical factors associated with staging errors after RC. PATIENTS AND METHODS: Characteristics of patients undergoing RC at University Health Network, Toronto, Canada (1992-2010) and University of Turku, Turku, Finland (1986-2005) were analysed. RESULTS: Among 602 patients undergoing RC, 306 (51%) had a discordance in clinical and pathological stages. Upstaging occurred in 240 (40%) patients and 192 (32%) patients were upstaged from organ-confined (OC) to non-organ-confined (nOC) disease. During the study period, upstaging became more common in both centres. In multivariate analyses, T2 disease at initial presentation (P= 0.001, odds ratio [OR]= 2.62, 95% confidence interval [CI]: 1.44-4.77), high grade disease (P= 0.01, OR = 2.85, 95% CI: 1.21-6.7), lymphovascular invasion (LVI) (P < 0.001, OR = 5.17, 95% CI: 3.48-7.68), female gender (P= 0.038, OR = 0.6, 95% CI: 0.38 0.97, and histological variants (P < 0.001, OR = 2.77, 95% CI: 1.6-4.8) were associated with a risk of upstaging from OC to nOC disease. Upstaged patients had worse survival rates than patients with correct staging. This was especially significant among patients with carcinoma invading bladder muscle before undergoing RC (16% vs 46% 10-year disease-specific mortality, P < 0.001). CONCLUSIONS: Upstaging is a common problem and unfortunately no improvements have been observed during the last two decades. LVI and the presence of histological variants are strong predictors of upstaging at the time of RC. Pathologists should be encouraged to report LVI and any histological variant at the time of TURBT. PMID- 22321342 TI - [A proposed model of ovarian tumorigenesis and a new theory on the origin of ovarian cancer]. PMID- 22321343 TI - [Preliminary study on the relationship between tubal intraepithelial carcinoma of the fimbria and pelvic high-grade serous carcinoma]. AB - OBJECTIVE: To explore the relationship between tubal intraepithelial carcinoma (TIC) of the fimbria and pelvic high-grade serous carcinoma. METHODS: All 34 cases of pelvic high-grade serous carcinoma with clear fimbria were evaluated from January 2009 to June 2010, including ovarian carcinoma (n = 26), tubal carcinoma (n = 7) and peritoneal carcinoma (n = 1). Among of these ovarian carcinomas, 12 cases were surface deposits and the other 14 cases within ovarian parenchyma. All 42 cases of non high-grade serous carcinoma in this period including 13 endometrioid ovary carcinomas, 11 clear cell ovary carcinomas, 11 mucinous ovary carcinomas, 6 low-grade serous ovary carcinomas, 1 low-grade serous tubal carcinoma, were also collected as a reference. The presence of tubal intraepithelial carcinomas was assessed. Based on the presence of TIC, high-grade serous ovary carcinomas were divided into TIC positive(+) and TIC negative(-) groups, and the clinical and pathological features of them were also evaluated. RESULTS: Fifteen cases (44%) were identified TIC in 34 high-grade pelvic serous carcinomas, and all of them were in the fimbria only, while none of TIC was found in control cases. There were significant difference between the two groups (chi(2) = 23.086, P = 0.000). Eleven cases (42%) were identified TIC in all 26 high-grade ovarian serous carcinomas, in which 8 cases with unilateral ovary carcinomas were associated with ipsilateral TIC, 2 cases with bilateral ovary carcinomas associated with unilateral TIC and one case with bilateral ovary carcinoma was associated with bilateral TIC. Four TIC (4/7) were identified in 7 cases with high-grade tubal serous carcinomas, and there was no presence of TIC in the 1 high-grade serous peritoneal carcinoma. Of all 26 high-grade ovarian serous carcinomas, 6/11 cases were surface deposits, and 5/11 were parenchyma tumors in TIC(+) group while 6/15 cases were surface deposits and 9/15 were parenchyma tumors in TIC(-) group, in which there were correlated in distribution of TIC between the two groups (P > 0.05). The average diameter of ovarian cancer were 6.9 and 6.5 cm between the two groups with no significant differences (t = 0.409, P = 0.690). CONCLUSION: TIC is specific to high-grade serous carcinomas and maybe have something to do with the pathogenesis of pelvic serous carcinomas. PMID- 22321344 TI - [Origin of ovarian epithelial inclusions and its relationship with the development of low-grade serous carcinoma]. AB - OBJECTIVE: To investigate the possible origin of ovarian epithelial inclusions and its relationship with the low-grade ovarian serous carcinoma. METHODS: By comparatively evaluating the morphologic (secretory and ciliated cell distribution) and immunophenotypic [using paired box gene 8 (PAX8), tubulin, calretinin, and Ki-67 as first antibodies] attributes of ovarian epithelial inclusions, the normal tubal epithelium, and the ovarian tumors, all adnexal tissues from a total of 198 patients were studied, including 116 adnexae removed for non-neoplastic indications, 53 serous cystadenomas, 44 serous borderline tumors, and 41 low-grade serous carcinomas, which were collected from Qilu Hospital of Shandong University and University of Arizona in USA. Immunohistochemical single staining was used to detect the expressions of PAX8, tubulin, calretinin, and Ki-67 in the two groups, while immunohistochemical double staining of PAX8/calretinin was used to figure out the immunophenotype of various ovarian epithelial inclusions in a more intuitive way. RESULTS: With immunohistochemical single staining of PAX8 and calretinin, the vast majority (90%, 54/60) of ovarian surface epithelia displayed a mesothelial phenotype [calretinin(+), PAX8(-)], whereas 10% (6/60) of the cases displayed foci with tubal phenotype [calretinin(-), PAX8(+)]. In contrast, most (79%, 728/921) of the ovarian epithelial inclusions displayed a tubal phenotype, though 21% (193/921) of the ovarian epithelial inclusions showed a mesothelial phenotype. It was further proved by immunohistochemical double staining of PAX8/calretinin. Secretory and ciliated cells were found in the ovarian epithelial inclusions with tubal phenotype. There was a progressive increase in the secretory/ciliated cells ratio and proliferative index, from ovarian epithelial inclusions/cystadenomas to borderline tumors to low-grade serous carcinoma, according to the expression of tubulin and Ki-67. CONCLUSIONS: The findings make a strong argument that the ovarian epithelial inclusions displaying a tubal phenotype with PAX8(+), calretinin(-) is likely derived from fallopian tube rather than through Mullerian metaplasia from ovarian surface epithelium. The increasing trend of secretory/ciliated cells ratio and proliferative index from ovarian epithelial inclusions/cystadenomas to borderline tumors to low-grade serous carcinoma indicates that the latter is a clonal expansion of secretory cells. Genetic and molecular studies are needed to further confirm these findings. PMID- 22321345 TI - [Strategy against pitfall in obstetric and gynecologic diagnosis and surgery]. PMID- 22321346 TI - [Clinical significance of two-tier grading system of ovarian serous carcinoma]. PMID- 22321347 TI - [Analysis of the cause and clinical characteristics of maternal cardiac arrest]. AB - OBJECTIVE: To analyze the cause and clinical characteristics of maternal cardiac arrest. METHODS: The data of all cases of maternal cardiac arrest from January 2005 to December 2009 in Third Affiliated Hospital of Guangzhou Medical College was retrospectively studied. RESULTS: (1) A total of 41 maternal cardiac arrests (6 in prenatal period, 2 in the first stage of labor, 7 in the third stage of labor, 26 in postpartum period) were included. All patients regained spontaneous circulation after basic life support. Twelve (29%) mothers survived. Twelve cardiac arrests occurred in the hospital, and the total delivery number from January 2005 to December 2009 was 17 101, with occurrence rate of 1:1425. (2) The causes of arrest were hemorrhagic shock (12, 29%), amniotic fluid embolism (7, 17%), severe preeclampsia/eclampsia (7, 17%), septic shock (6, 15%), cardiac disease (2, 5%), unidentified cause (2, 5%) and other occasional causes. (3) Thirty-seven (90%) in-hospital maternal cardiac arrest occurred in operation room (16, 39%), ICU (7, 17%), maternity wards (6, 15%), delivery room (5, 12%) and the emergency room (3, 7%). Three (7%) arrest occurred out of hospital and one in the ambulance. Maternal survival rate was 2/3 in the emergency room, 8/16 in the operation room, 1/5 in the maternity wards, and 1/6 in the delivery room. No mother survived in ICU, ambulance or out of hospital. (4) Five of the 12 survived women showed ischemic encephalopathy after cardiac arrest and one of them developed cerebral infarction in the right corona radiate. (5) In 4 of the 8 cases of cardiac arrest in pregnancy, perimortem caesarean section (PMCS) was performed. In the four PMCS, 2 mothers and 2 children survived. In the 4 cases that PMCS was not carried out, no infant survived. CONCLUSIONS: Hemorrhagic shock, severe preeclampsia and eclampsia, amniotic fluid embolism are the major obstetric causes of maternal cardiac arrest. Septic shock and cardiac diseases are the major non-obstetric causes. Cardiac arrests occurred in emergency room and operation room has a higher maternal survival rate than those occurred in the delivery room and maternity wards. Timely PMCS may ensure the optimal outcome for mothers and fetuses. PMID- 22321348 TI - [Predictive value of cervical length by transvaginal sonography for preterm pregnancy during mid- and late-trimester of pregnancy]. AB - OBJECTIVE: To study the value of cervical length (CL) by transvaginal sonography in the mid-trimester and late-trimester for the prediction of preterm delivery. METHODS: The CL was measured by transvaginal sonography for 5277 pregnant women between 22 - 24 weeks and 28 - 32 weeks gestation, who were prenatal cared and delivered at the First Hospital of Peking University from June 2008 to November 2009. The pregnancy outcomes were followed, and the relationship between CL and preterm delivery and preterm premature rupture of membrane was studied. RESULTS: (1) The incidence of preterm delivery was 5.4% (289/5370) total, among of them the incidence of therapeutic preterm delivery was 1.7% (93/5370), spontaneously preterm delivery was 1.2% (62/5370), and preterm premature rupture of membrane was 2.5% (134/5370). There are 4 cases (4/5370) who occured late abortion. (2) Excluding the 93 women who had therapeutic preterm delivery, the mean CL of 22 - 24 weeks was (38.8 +/- 4.0) mm. The relative risk for preterm delivery when the CL < 30 mm was 5.2, when CL < 25 mm, the relative risk was 11.1, and when CL < 15 mm the relative risk for preterm delivery was 13.8. The average CL during 28-32 weeks of gestation was (34.6 +/- 4.8) mm, was significantly shorter than that of 22 - 24 weeks (P < 0.05). During this period the relative risk for preterm delivery when the CL < 30 mm was 6.9, when CL < 25 mm, the relative risk was 11.1, and when CL < 15 mm the relative risk for preterm delivery was 20.0. (3) A CL < 30 mm as the cut-off value for predicting preterm delivery during 22 - 24 weeks of gestation has only a 3% sensitivity and 19% positive predictive value, but had a 99% specificity and 96% negative predictive value. The sensitivity, positive predictive value, specificity and negative predictive value for a CL < 30 mm as the cut-off value for predicting preterm delivery during 28 - 32 weeks of gestation was 33%, 21%, 95% and 97% respectively. (4) The total number of preterm premature rupture of membrane pregnant women was 134 (2.5%), who had a mean CL of (38.4 +/- 4.7) mm during 22 - 24 weeks of gestation, was similar with the women without preterm premature rupture of membrane (PPROM), but during 28 - 32 weeks of gestation the women who occured PPROM had a mean cervical length of (30.6 +/- 8.1) mm, and was significantly shorter than that of women without PPROM (34.7 +/- 4.6) mm. CONCLUSIONS: (1) CL in 28 - 32 weeks of gestation is significantly shorter than that of in the mid-gestation, but more than 90% of women has a CL >= 30 mm. (2) The shorter the CL is, the greater the relative risk of preterm delivery. According to different CL for clinical consulting objective relative risk could be provide. (3) The CL during 28 - 32 weeks of gestation can also predict preterm delivery, the sensitivity is obviously better than that of 22 - 24 weeks of gestation. (4) The CL during 28 - 32 weeks of gestation is valuable for predicting of PPROM. PMID- 22321349 TI - [Relationship between factors of labour pain and delivery outcomes]. AB - OBJECTIVE: To evaluate factors associated with labor pain and delivery outcomes. METHODS: From Jul. to Dec. 2009, 111 normal singleton cephalic presentation pregnancies (including 5 elderly parturient) who delivered at the Department of Obstetrics and Gynecology, Second Affiliated Hospital, Zhejiang Chinese Medical University were enrolled in this study to evaluate the relationship between factors of labor pain and delivery outcomes. The labor pain of latent phase and active phase were scored by the visual analogue scale (VAS). Factors associated with pain included the age of parturient, the number of gravidity and parity, occupation, education profile, dwell location, etc. The questionnaire was designed by ourselves. Childbirth awareness, psychological preparation of delivery, emotional controllability, couple relationship, the relationship of parturient and mother-in-law, the relationship of parturient and parents, family economic status, use of sedative during the labor process and delivery outcomes were collected and analyzed. RESULTS: (1) Factors associated with pain: in the latent phase, the rate of moderate labour pain of 1/5 in women with more than 35 years old was statistically lower than 76.4% (81/106) in suitable age group (P < 0.05). The women with a good understanding about delivery had a statistically lower rate of moderate pain of 64.7% (44/68) than 88.4% (38/43) of those having a poor understanding (P < 0.05). The women who had a better couple relationship had a significantly higher rate of moderate pain of 77.2% (78/101) than 4/10 of those who had a general couple relationship (P < 0.05). There was significant difference in rate of moderate pain between pluripara group (50.0%, 11/22) and primipara group (79.8%, 71/89; P < 0.01). In the active phase, women with tense, scared or a poor emotion control expressed significantly severe labour pain (59.0%, 36/61) than 35.6% (16/45) in well-prepared group. The rate of severe labour pain in good control of emotion group of 44.8% (43/96) was a statistically lower than 9/10 in poor control group. There was a statistically lower severe labour pain in women given by sedatives (29.2%, 7/24) than 54.9% (45/82) in women without sedatives treatment (P < 0.05). (2) Delivery outcomes: in latent phase, the rates of fetal distress and cesarean section were 36.6% (30/82) and 39.0% (32/82) in moderate pain group, which were significantly higher than 13.8% (4/29) and 17.2% (5/29) in mild pain group. In active phase, the rate of fetal distress, cesarean section and postpartum hemorrhage were 36.5% (19/52), 40.4% (21/52) and 13.5% (7/52) in severe pain group, which were significantly higher than [18.5% (10/54); 20.4% (11/54); 0] in moderate pain group (P < 0.05). CONCLUSIONS: Women with poor understanding of delivery, tense, scared, poor emotion control, young age and uniparous have severe labour pain. Sedative use could alleviate pain in active phase. Women with mild labour pain have good delivery outcomes. PMID- 22321350 TI - [Relationship between the expression of human leukocyte antigen G and preeclampsia]. AB - OBJECTIVES: To detect the expression of human leukocyte antigen-G (HLA-G) in tissues from pregnant women with preeclampsia and discuss the relationship between HLA-G and preeclampsia. METHODS: Pregnant women with preeclampsia in Maternal and Child Health Hospital of Shaanxi Province from March 2009 to December 2009 were included. Eight were included into mild preeclampsia groups and 22 were included into severe preeclampsia group. And 30 age-matched normal pregnancies were referred as the control group. All women in the three groups received cesarean section. The soluble HLA-G (sHLA-G) levels in peripheral blood, umbilical blood and amniotic fluid were examined by ELISA; the expressions of HLA G protein in placenta, fetal membrane and umbilical cord were examined by western blot. RESULTS: (1) The sHLA-G levels in peripheral blood, umbilical blood and amniotic fluid in each group. The sHLA-G levels in peripheral blood in mild and severe preeclampsia group were (50 +/- 14) and (30 +/- 6) ug/L respectively, and the sHLA-G levels in umbilical blood were (34 +/- 10) and (26 +/- 8) ug/L respectively. All were significantly lower than those in the control group (P < 0.01), which were (100 +/- 16) and (70 +/- 9) ug/L respectively. There was also statistical difference between mild and severe preeclampsia group (P < 0.01). Although the sHLA-G level in umbilical blood of severe preeclampsia group was lower than that in mild preeclampsia group, there was no statistical difference (P > 0.05). The sHLA-G levels in amniotic fluid in mild and severe preeclampsia groups were (26 +/- 7) and (25 +/- 5) ug/L respectively, which were lower than that in the control group (27 +/- 6) ug/L, but the differences were not significant (P > 0.05). There was no statistical difference between mild and severe preeclampsia groups (P > 0.05). (2) The expression levels of HLA-G protein in placenta, fetal membrane and umbilical cord in each group. The expression levels of HLA-G in placenta and fetal membrane in the control group were 1.59 +/- 0.36 and 0.42 +/- 0.09 respectively. The expression of HLA-G in placenta was significantly higher than that in fetal membrane (P < 0.05). The expression level of HLA-G in umbilical cord in the control group was 0.24 +/- 0.17, statistically different from those in placenta and fetal membrane, respectively (P < 0.01). The expression levels of HLA-G in placenta in mild and severe preeclampsia groups were 0.78 +/- 0.21 and 0.29 +/- 0.17 respectively, significantly different from the control group (P < 0.01). There was no expression of HLA-G in fetal membrane and umbilical cord in mild and severe preeclampsia groups. CONCLUSIONS: The expressions of HLA-G in the peripheral blood, umbilical blood and placenta in women with preeclampsia are significantly lower than those in normal pregnant women. The abnormal expression of HLA-G might be associated with the pathogenesis of preeclampsia. PMID- 22321351 TI - [Study on association of functional polymorphisms in Foxp3 gene with the susceptibility to unexplained recurrent spontaneous abortion]. AB - OBJECTIVE: To investigate the association between the functional polymorphisms of Foxp3 gene and unexplained recurrent spontaneous abortion (URSA). METHODS: PCR restriction fragment length polymorphism (rs3761548, rs2294021) and PCR with sequence-specific primers (rs2232365, rs5902434) were used to detect four polymorphisms of Foxp3 in 146 URSA cases and 112 normal controls. RESULTS: (1) The frequencies of rs3761548A/C were 10.3%, 22.3% in genotype C/C, 38.4%, 40.2% in genotype A/C and 51.4%, 37.5% in genotype A/A between URSA patients and normal controls; the frequencies of rs2232365A/G were 5.5%, 15.2% in genotype A/A, 47.9%, 50.0% in genotype A/G, 46.6%, 34.8% in genotype G/G between URSA patients and normal controls; they all reached statistical difference (P < 0.05). The carriers of rs3761548A allele and rs2232365G allele increased the risk of URSA (OR = 1.73, 1.61;all P < 0.05). (2) There was no difference in the genotypic distribution of rs5902434del/ATT polymorphism between cases and controls (P = 0.10), but the frequency of del allele in URSA was statistically increased than that of controls (71.2%, 62.5%;OR = 1.49, P = 0.04). (3) There was no different distribution in 3 genotypes (C/C, T/C, T/T) and 2 alleles (T and C) of rs2294021T/C between URSA patients and normal controls (P = 0.18 and 0.08). (4) Estimated haplotype frequency distribution of rs5902434del/ATT, rs3761548A/C and rs22323565A/G showed haplotype del-A-G conferring the susceptibility to URSA (OR = 2.51, P < 0.01) but haplotype del-C-G and ATT-A-A could provide protection on URSA (OR = 0.18, 0.22; all P < 0.01). CONCLUSION: Functional polymorphisms of Foxp3 gene could probably confer the susceptibility to URSA, by altering Foxp3 function and (or) its expression. PMID- 22321352 TI - [Effect of the Wnt/LRP5/beta-catenin signaling pathway on the pathogenesis of postmenopausal osteoporosis]. AB - OBJECTIVE: To investigate the role of the Wnt/LRP5/beta-catenin signaling pathway in the pathogenesis of postmenopausal osteoporosis. METHODS: Fifty female Wistar rats aged 6-month-old, were randomly divided into control group (NS, n = 24) and ovariectomized group (NOVX, n = 26), NOVX underwent bilateral ovariectomy. At 0, 4 and 8 weeks, all of rats were measured blood estrogen (E(2)) and bone mineral density (BMD), 4 and 8 weeks, low density lipoprotein receptor-related protein 5 (LRP5), beta-catenin and Runx2 mRNA in bone were measured respectively by reverse transcription (RT)-PCR. RESULTS: In 4 and 8 weeks, compared with NS which had (117 +/- 29) and (114 +/- 15) pmol/L in E(2) level, (0.098 +/- 0.016) and (0.095 +/- 0.028) g/cm(2) in BMD, NOVX had significantly decreased to (92 +/- 15) and (95 +/- 22) pmol/L in E(2) level (P < 0.05), (0.076 +/- 0.016) and (0.052 +/- 0.013) g/cm(2) in BMD values (P < 0.01). And bone tissue LRP5, beta-catenin and Runx2 mRNA expression was 1.02 +/- 0.06, 1.04 +/- 0.05, 1.07 +/- 0.21 in NS, NOVX was significantly reduced to 0.97 +/- 0.04, 0.58 +/- 0.05, 0.86 +/- 0.03 (P < 0.05). CONCLUSION: Wnt/LRP5/beta-catenin signaling pathway may be important in the pathogenesis of postmenopausal osteoporosis. PMID- 22321353 TI - [Culture and identification of microvascular endothelial cells from human endometriosis]. AB - OBJECTIVE: To establish the methods of isolating and culturing human ovarian endometriosis-derived microvascular endothelial cells (OEMEC). METHODS: The tissues of human endometriotic cyst of ovary were finely minced with scissors, then digested by collagenase I, II and trypsin-ethylene diamine tetraacetic acid (EDTA). The cells were purified by using centrifugation of 2000 r/min speed. OEMEC were identified by light microscope and transmission electron microscope observing CD(34), FVIII-Rag and Weibel-Palade in microvascular endothelial cells. RESULTS: The OEMEC grew as confluent monolayer like cobblestones under light microscope. CD(34) and FVIII-Rag were expressed strongly, and the percentages of CD(34) and FVIII-Rag positive cells were 91.4% and 92.5%. Weibel-Palade bodies could be observed under transmission electron microscope. The time of cell doubling proliferation was 4.5 days. CONCLUSION: The established system of isolating OEMEC would provide lab base for studying the mechanisms of angiogenesis in endometriosis lesions. PMID- 22321354 TI - Astigmatism correction: Laser in situ keratomileusis versus posterior chamber collagen copolymer toric phakic intraocular lens implantation. AB - PURPOSE: To compare the stability and predictability of astigmatism correction between toric phakic intraocular lens (pIOL) implantation and laser in situ keratomileusis (LASIK). SETTING: Nagoya Eye Clinic, Nagoya, Japan. DESIGN: Comparative case series. METHODS: Consecutive patients who had Implantable Collamer Lens pIOL implantation or LASIK were divided into 3 subgroups according to the amount of refractive cylinder correction (low, 0.00 to 1.25 diopters [D]; moderate, 1.50 to 2.75 D; high, >= 3.00 D). Manifest refraction was measured preoperatively and 1, 3, 6, and 12 months postoperatively. Based on these data, the predictability and stability of the refractive cylinder correction, error of the refractive cylinder correction, and error of the refractive cylinder correction axis were evaluated. RESULTS: The study comprised 338 eyes (196 patients) in the toric pIOL group and 351 eyes (202 patients) in the LASIK group. In the moderate cylinder subgroup, more eyes were corrected within +/- 0.50 D of the postoperative refractive cylinder in the LASIK group (132 eyes [91%]) than in the toric pIOL group (111 eyes [79%]). In the high refractive cylinder subgroup, the error of the refractive cylinder correction in the LASIK group was significantly higher than in the toric pIOL group (P=.032). The postoperative manifest refractive cylinder did not change in either group during the follow-up period. CONCLUSIONS: The stability of the refractive cylinder after toric pIOL implantation was as high as after LASIK. Although predictability in the LASIK group was higher than in the toric pIOL group in eyes with moderate refractive cylinder, the toric pIOL group had higher predictability than the LASIK group in eyes with high refractive cylinder. PMID- 22321355 TI - Healing changes in clear corneal cataract incisions evaluated using Fourier domain optical coherence tomography. AB - PURPOSE: To evaluate the long-term wound-healing changes in clear corneal cataract incisions using Fourier-domain optical coherence tomography (OCT). SETTING: Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA. DESIGN: Case series. METHODS: Multiple OCT images were obtained in consecutive eyes that had phacoemulsification 1 day to 180 months previously. The incision midpoint was measured with OCT. The presence of Descemet membrane detachment, posterior wound gape, and posterior wound retraction was assessed. The depth of wound retraction along the incision and the radial length of the incision were measured. The percentage of wound retraction relative to radial incision length was calculated. RESULTS: Descemet membrane detachment was present in 37.1% of eyes 1 day postoperatively and in 4.5% of eyes at 1 to 3 months (P=.005); it was absent after 3 months. Posterior wound gape appeared in 85.7% of eyes at 1 day and in 31.8% at 1 to 3 months (P<.001); it was absent after 3 months. Posterior wound retraction appeared in 33.3% of eyes at 2 to 3 weeks, in 75.0% at 1 to 3 years, and in 90.5% after 3 years (P<.001). The mean wound retraction was 120 MUm +/- 46 (SD) (range 24 to 225 MUm), which was 7.5% +/- 3.1% (range 2.0% to 13.4%) of the radial incision length. CONCLUSION: Descemet membrane detachment and posterior wound gape appeared in the early postoperative period and persisted for up to 3 months, whereas posterior wound retraction developed later and was present in more than 90% of eyes after 3 years, indicating long-term wound remodeling. PMID- 22321356 TI - The influence of proximal ulnar morphology on elbow range of motion. AB - BACKGROUND: Physiologic dorsal apex angulation of the proximal ulna is present in 96% of the population. We hypothesize that a correlation exists between the physiologic dorsal ulnar angulation and elbow range of motion (ROM). METHODS: Fifty healthy adults underwent bilateral lateral elbow radiographs in neutral forearm rotation in the following positions: terminal flexion (TF), 90 degrees of flexion, and terminal extension (TE). The proximal ulna dorsal angulation (PUDA), TF, and TE were measured on the digital lateral radiographs by 2 independent observers. ROM was calculated as the difference between TF and TE measurements. Subjects were divided into 2 groups: those with PUDA measurements less than the median and those with PUDA measurements equal to or greater than the median. The relationship between the PUDA and TE, TF, and ROM was evaluated by use of Pearson correlation coefficients. RESULTS: The mean age of the cohort was 31 +/- 9 years, and there were 30 women among the 50 volunteers. The sample of 100 elbow radiographs had a mean TF of 150.8 degrees +/- 4.5 degrees , a mean TE (ie, flexion contracture) of 11.5 degrees +/- 7.3 degrees , and a mean ROM of 139.3 degrees +/- 8.4 degrees . The mean PUDA was 5.2 degrees +/- 2.8 degrees . Elbows with a greater PUDA had significantly less TE (r = 0.381, P <= .001) and ROM (r = -0.351, P <= .001). The group of elbows with a lesser PUDA had better TE (9.4 degrees vs 13.6 degrees , P = .004) and ROM (142.0 degrees vs 136.7 degrees , P = .001) than elbows with a greater PUDA. CONCLUSION: The increasing magnitude of the PUDA is associated with decreased maximal elbow extension and global elbow ROM. PMID- 22321357 TI - One-year efficacy and safety study of a 1.62% testosterone gel in hypogonadal men: results of a 182-day open-label extension of a 6-month double-blind study. AB - INTRODUCTION: A new formulation of testosterone gel (1.62% testosterone gel) with increased viscosity and reduced volume of application has been shown to be safe and efficacious after 182 days of use in a phase 3, double-blind study in adult hypogonadal males. AIM: The objective of this study was to evaluate the efficacy and safety of the 1.62% testosterone gel after daily application to the skin in a 182-day (6-month) open-label extension of the initial 182-day double-blind study. METHODS: One hundred and sixty-three subjects, aged 26 to 77 years, continued on active (Continuing Active subjects) 1.62% testosterone gel for the remainder of the study (364 days total). In 28 subjects who had previously received placebo (Formerly Placebo subjects), the dose was titrated to normal levels of serum total testosterone (300-1,000 ng/dL). Dose adjustments for both groups were allowed at specific visits to maintain serum testosterone within a normal range. MAIN OUTCOME MEASURE: The main outcome measure was the percentage of subjects with serum total testosterone average concentrations (C(av) ) within the normal range at day 364. RESULTS: On day 364, 77.9% (95% confidence interval: 70.0, 84.6) of the Continuing Active subjects and 87.0% (66.4, 97.2) of the Formerly Placebo subjects had C(av) values within the eugonadal range. The 1.62% testosterone gel was safe and well tolerated in this study. CONCLUSION: Treatment with 1.62% testosterone gel for up to 1 year (182 days for the Formerly Placebo subjects, 364 days for the Continuing Active subjects) was safe and efficacious, resulting in >77% of treated subjects achieving normal serum testosterone levels at final visit. PMID- 22321358 TI - Gamma-aminobutyric acid (GABA)-B receptor 1 in cerebellar cortex of essential tremor. AB - Some reports suggest cerebellar dysfunction as the basis of essential tremor (ET). Several drugs with the action of gamma-aminobutyric acid (GABA) are known to improve ET. Autopsy studies were performed on brains from nine former patients followed at the Movement Disorders Clinic Saskatchewan, Canada, and compared with five normal control brains. We aimed to measure the concentration of GABA B receptor 1 (GBR1) in the brains of patients who had had ET and to compare them to the GABA concentration in brains of controls. Western blot was used to determine the expression of GBR1 in cerebellar cortex tissue. We found that compared to the controls, the ET brains had three different patterns of GBR1 protein concentration--two with high, four comparable, and three with marginally low levels. There was no association between the age of onset, severity or duration of tremor, the response to alcohol or other drugs and GBR1 level. Thus, we conclude that our study does not support that GBR1 is involved in ET. Further studies are needed to verify these results. PMID- 22321359 TI - Imaging modalities in high-grade gliomas: pseudoprogression, recurrence, or necrosis? AB - High grade gliomas (HGG) frequently recur regardless of treatment. Radiological detection of progressive disease (PD) is challenging due to the possibility of therapy-related MRI changes including: pseudoprogression (PP) and radiation necrosis (RN). Both may mimic PD. We undertook a literature review to examine existing data regarding imaging modalities and their ability to distinguish between PP, RN and PD. The review revealed 26 articles comparing the value of imaging modalities used to differentiate PP, RN and PD. Overall, conventional MRI and (18)fluorine-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) were more sensitive, while thallium single photon emission CT (SPECT) was more specific in differentiating PD from PP and RN. However, further prospective studies comparing the clinical utility of MRI, PET, and SPECT are needed to establish the most reliable diagnostic tool for the differentiation of PP, RN and PD in HGG. PMID- 22321360 TI - Arachnoid cyst associated with painful tic convulsif. AB - Combined clinical presentation of hemifacial spasm and ipsilateral trigeminal neuralgia is known as painful tic convulsif (PTC). It is a rare condition and the most common cause is vascular compression. We report an arachnoid cyst of the posterior fossa that caused PTC in a 50-year-old woman. Her radiological evaluation revealed a median, well-circumscribed, cystic lesion of the posterior fossa suggestive of arachnoid cyst, pushing the cerebellum and brainstem anteriorly. Midline suboccipital craniotomy and marsupialization of cyst was performed with complete recovery of symptoms. To our knowledge, this is the first report of a retrocerebellar arachnoid cyst causing PTC. PMID- 22321361 TI - An endovascular approach to ruptured aneurysms of the circumferential branch of the basilar artery. AB - Aneurysms of the basilar perforating arteries are uncommon and those of the circumferential artery are particularly rare. Microsurgical clipping or trapping is the preferred treatment as these aneurysms are usually not accessible for endovascular treatment. We report two patients with ruptured aneurysms arising from the basilar circumferential artery. The first patient, a 66-year-old male, presented with a prepontine hematoma and a delayed filling aneurysm of the basilar circumferential artery. The second patient, a 28-year-old female, presented with a narrow-neck aneurysm of the basilar circumferential artery, associated with an arteriovenous malformation in the left cerebellum. Both patients were treated successfully with endovascular coiling, flow was preserved in the perforating parent vessels and the patients had excellent outcomes. This is the first report of this type of aneurysm being successfully treated by endovascular coiling. The treatment challenges regarding microsurgical and endovascular approaches are discussed. PMID- 22321362 TI - Corpectomy with titanium cage reconstruction in the cervical spine. AB - Multi-level anterior cervical discectomy and fusion (ACDF) has been utilized by many surgeons to address multi-level cervical disease with the use of autograft or allograft. High failure rates have been reported in three-level decompressions when autograft is used, which increases with the use of allograft. This has led many surgeons to advocate anterior cervical corpectomy with strut grafting where only two surfaces are needed for fusion compared to the multiple surfaces required for multi-level ACDF. We retrospectively evaluated the efficacy of titanium cage use with autologous bone graft (resected vertebral bodies) and anterior cervical plating in 38 consecutive patients (aged 18-73 years) undergoing cervical decompression and corpectomy. Medical records were examined along with an outcome interview conducted in-person or by phone. Postoperative immobilization was achieved with a rigid cervical collar. Fusion was assessed by antero-posterior (AP), lateral, and flexion-extension radiographs and cervical spine CT scans. Fusion was assessed by AP, lateral, and flexion-extension radiographs and cervical spine CT scans. Clinical results included an exit interview. Solid bony fusion with graft incorporation was found in 37 of 38 patients (97.5%) at six months and 100% in one year. Compared to preoperative levels, 84% of patients rated their overall quality of life to have improved by 50% or greater and would have the same surgery again given the same conditions. There were few complications. Thus, titanium cage reconstruction with the use of autologous bone from a corpectomy and the use of an anterior cervical plate is an effective means of reconstruction after decompressive cervical corpectomy, and we conclude this is a viable alternative to multi-level ACDF or to procedures involving long strut grafts obtained from the patient or bone bank. PMID- 22321363 TI - Slowly progressive Foix-Chavany-Marie syndrome as a precursor of a primary progressive aphasia. AB - Foix-Chavany-Marie syndrome (FCMS) is a rare neurological condition usually associated with bilateral ischemic lesions of the anterior frontoparietal operculum. Here, we present a patient with slowly progressive FCMS owing to focal brain atrophy who developed a language disorder similar to that seen in a primary progressive aphasia. PMID- 22321364 TI - Primary medulla oblongata germinoma in a male patient. AB - Germinoma mainly occurs in the pituitary stalk, pineal region, and basal ganglia. Sex predominance of the tumor in males in the pineal region and basal ganglia is well known. Primary germinoma of the medulla oblongata is rare, with only eight reports, mostly in females. We report the second male patient with primary medulla oblongata germinoma, without chromosomal abnormality, who was successfully treated with surgery, chemotherapy, and radiotherapy. PMID- 22321365 TI - An observational study on electrolyte disorders in the acute phase of ischemic stroke and their prognostic value. AB - Data on electrolyte disorders in neurological conditions and in acute stroke are somewhat scanty and not easily compared. In our Stroke Unit we studied patients hospitalized within six hours of the onset of an acute ischemic stroke and recorded their demographic and clinical data. Blood test results were recorded before any pharmacological therapy. A total of 475 individuals (256 M, 219 F; range: 14-96 years) treated over a period of 18 consecutive months, were selected. According to multiple logistic regression analysis, the baseline National Institute of Health Stroke Scale (NIHSS) score (odds ratio [OR]=1.33; 95% confidence interval [CI]: 1.22-1.44) and natremia alterations (OR=6.89; 95% CI=1.94-24.40) were associated with higher odds of death. Based on the ordinal logistic regression analysis, the baseline NIHSS score (OR=1.07; 95% CI=1.03 1.10) and baseline hypernatremia (OR=9.69; 95% CI=1.55-60.69) were related to early neurological worsening. Our work suggests an association between serum sodium alterations and mortality, and between high sodium levels and neurological clinical impairment, in the acute phase of an ischemic stroke. PMID- 22321366 TI - Clinical features and pathological characteristics of amygdala enlargement in mesial temporal lobe epilepsy. AB - Although the hippocampus is considered an important site of seizures in mesial temporal lobe epilepsy (mTLE), the amygdala may also have a significant role. Amygdala enlargement is occasionally found in patients with mTLE, and volumetric detection of amygdala enlargement has been documented in "image-negative" patients with TLE. However, only limited data have been reported on the clinical features, surgical outcomes, and pathological characteristics in patients with mTLE with amygdala enlargement. We recruited 12 patients who had undergone surgical treatment for refractory epilepsy with radiological evidence of amygdala enlargement, and 11 became seizure free. All patients showed homogenously increased amygdala volumes on MRI without enhancement and underwent surgical treatment for mTLE. Pathology results revealed that eight patients had focal cortical dysplasia (FCD), two had ganglioglioma, one had oligodendroglioma, and one had astrocytoma. The clinical features and MRI findings were largely indistinguishable between the patients with brain tumors and those with FCD, but the patients with brain tumors tended to be younger at the time of seizure onset. Our study shows that surgical treatment of epilepsy in patients with amygdala enlargement usually has a favorable outcome. FCD was the most frequent pathological diagnosis in these patients. However, a brain tumor should be considered in the differential diagnosis, especially in young patients, because it is often difficult to differentiate FCD from a brain tumor on radiological features. PMID- 22321367 TI - Unusual spinal metastases from an adenoid cystic carcinoma of the maxillary sinus. AB - Adenoid cystic carcinoma (ACC), the second most common cancer occurring in the sinonasal tract, is an aggressive malignancy with a poor five-year survival rate. Spinal metastases to the vertebral column related to this cancer are rare. This report presents a patient with maxillary sinus carcinoma with vertebral metastases at the thoracic level and compression of the spinal cord seven years after surgical resection of the primary tumor. Eleven years after detection of the primary tumor the patient is still able to walk. The role of decompression and/or fusion in spinal metastases with neurologic deficits is still under debate, although recent studies have confirmed the beneficial role of surgical intervention in selected patients. This report represents an example of modern individual treatment of an aggressive tumor in a palliative situation. The epidemiology, clinical findings, treatment and outcome of this atypical distant metastasis in long-term survivors are presented. PMID- 22321368 TI - Computed tomographic angiography for patients with acute spontaneous intracerebral hemorrhage. AB - With the advanced technology of multi-slice CT scans, we explored the effectiveness of CT angiography (CTA) in place of digital subtraction angiography (DSA) in patients with acute spontaneous intracerebral hemorrhage (ICH). We performed a computerized PubMed search of the literature from inception to 27 July 2011 to find reports of similar comparative studies and performed a meta analysis of diagnostic accuracy. The pooled sensitivity was 97.0% (95% confidence interval [CI]: 93.2-99.1%), specificity was 98.9% (95% CI: 97.0-99.7%), accuracy was 98.2% (95% CI: 96.6-99.2%), positive predictive value was 97.8% (95% CI: 94.2 99.5%) and negative predictive value was 98.5% (95% CI: 96.6-99.5%). The false negative rate was 1% (95% CI: 0.4-2.6%). We concluded that CTA with venography could replace DSA as the initial vascular investigation in patients presenting with spontaneous ICH during the acute phase. Future studies should focus on whether refinement of the techniques could preclude the false negative results. PMID- 22321369 TI - Increased expression of valosin-containing protein in the skin of patients with amyotrophic lateral sclerosis. AB - Valosin-containing protein (VCP) may have a pivotal role in ubiquitin-dependent protein degradation and is implicated in the pathogenesis of neurodegenerative diseases. Skin studies from patients with amyotrophic lateral sclerosis (ALS) have shown unique abnormalities. We undertook a quantitative immunohistochemical study of VCP in the skin from patients with ALS and control participants. The proportion of VCP-positive (VCP+) cells in the epidermis in patients with ALS was significantly higher (p<0.001) than in controls. There was a significant positive relationship (r=0.59, p<0.01) between this proportion and duration of illness in patients with ALS. The optical density of VCP+ cells in the epidermis in patients with ALS was higher (p<0.001) than in controls. There was a significant positive relationship (r=0.61, p<0.01) between the immunoreactivity and duration of illness in patients with ALS. These data suggest that changes in VCP identified in skin from patients with ALS are likely to be related to the disease process. PMID- 22321370 TI - Preservation of NADH ubiquinone-oxidoreductase activity by Src kinase-mediated phosphorylation of NDUFB10. AB - The tyrosine kinase Src is upregulated in several cancer cells. In such cells, there is a metabolic reprogramming elevating aerobic glycolysis that seems partly dependent on Src activation. Src kinase was recently shown to be targeted to mitochondria where it modulates mitochondrial bioenergetics in non-proliferative tissues and cells. The main goal of our study was to determine if increased Src kinase activity could also influence mitochondrial metabolism in cancer cells (143B and DU145 cells). We have shown that 143B and DU145 cells produce most of the ATP through glycolysis but also that the inhibition of OXPHOS led to a significant decrease in proliferation which was not due to a decrease in the total ATP levels. These results indicate that a more important role for mitochondria in cancer cells could be ensuring mitochondrial functions other than ATP production. This study is the first to show a putative influence of intramitochondrial Src kinase on oxidative phosphorylation in cancer cells. Indeed, we have shown that Src kinase inhibition led to a decrease in mitochondrial respiration via a specific decrease in complex I activities (NADH ubiquinone oxidoreductase). This decrease is associated with a lower phosphorylation of the complex I subunit NDUFB10. These results suggest that the preservation of complex I function by mitochondrial Src kinase could be important in the development of the overall phenotype of cancer. PMID- 22321371 TI - The role of Deinococcus radiodurans RecFOR proteins in homologous recombination. AB - Deinococcus radiodurans exhibits extraordinary resistance to the lethal effect of DNA-damaging agents, a characteristic attributed to its highly proficient DNA repair capacity. Although the D. radiodurans genome is clearly devoid of recBC and addAB counterparts as RecA mediators, the genome possesses all genes associated with the RecFOR pathway. In an effort to gain insights into the role of D. radiodurans RecFOR proteins in homologous recombination, we generated recF, recO and recR disruptant strains and characterized the disruption effects. All the disruptant strains exhibited delayed growth relative to the wild-type, indicating that the RecF, RecO and RecR proteins play an important role in cell growth under normal growth conditions. A slight reduction in transformation efficiency was observed in the recF and recO disruptant strains compared to the wild-type strain. Interestingly, disruption of recR resulted in severe reduction of the transformation efficiency. On the other hand, the recF disruptant strain was the most sensitive phenotype to gamma rays, UV irradiation and mitomycin C among the three disruptants. In the recF disruptant strain, the intracellular level of the LexA1 protein did not decrease following gamma irradiation, suggesting that a large amount of the RecA protein remains inactive despite being induced. These results demonstrate that the RecF protein plays a crucial role in the homologous recombination repair process by facilitating RecA activation in D. radiodurans. Thus, the RecF and RecR proteins are involved in the RecA activation and the stability of incoming DNA, respectively, during RecA-mediated homologous recombination processes that initiated the ESDSA pathway in D. radiodurans. Possible mechanisms that involve the RecFOR complex in homologous intermolecular recombination and homologous recombination repair processes are also discussed. PMID- 22321372 TI - Comments on type I bare lymphocyte syndrome. PMID- 22321373 TI - Using CF11 cellulose columns to inexpensively and effectively remove human DNA from Plasmodium falciparum-infected whole blood samples. AB - BACKGROUND: Genome and transcriptome studies of Plasmodium nucleic acids obtained from parasitized whole blood are greatly improved by depletion of human DNA or enrichment of parasite DNA prior to next-generation sequencing and microarray hybridization. The most effective method currently used is a two-step procedure to deplete leukocytes: centrifugation using density gradient media followed by filtration through expensive, commercially available columns. This method is not easily implemented in field studies that collect hundreds of samples and simultaneously process samples for multiple laboratory analyses. Inexpensive syringes, hand-packed with CF11 cellulose powder, were recently shown to improve ex vivo cultivation of Plasmodium vivax obtained from parasitized whole blood. This study was undertaken to determine whether CF11 columns could be adapted to isolate Plasmodium falciparum DNA from parasitized whole blood and achieve current quantity and purity requirements for Illumina sequencing. METHODS: The CF11 procedure was compared with the current two-step standard of leukocyte depletion using parasitized red blood cells cultured in vitro and parasitized blood obtained ex vivo from Cambodian patients with malaria. Procedural variations in centrifugation and column size were tested, along with a range of blood volumes and parasite densities. RESULTS: CF11 filtration reliably produces 500 nanograms of DNA with less than 50% human DNA contamination, which is comparable to that obtained by the two-step method and falls within the current quality control requirements for Illumina sequencing. In addition, a centrifuge free version of the CF11 filtration method to isolate P. falciparum DNA at remote and minimally equipped field sites in malaria-endemic areas was validated. CONCLUSIONS: CF11 filtration is a cost-effective, scalable, one-step approach to remove human DNA from P. falciparum-infected whole blood samples. PMID- 22321374 TI - Corrective force analysis for scoliosis from implant rod deformation. AB - BACKGROUND: Scoliosis is a serious disease in which a human spine is abnormally deformed in three dimensions with vertebral rotation. Surgical treatment is attained when the scoliotic spine is corrected into its normal shape by implant rods and screws fixed into the vertebrae. The three-dimensional corrective forces acting at the screws deformed the implant rod during the surgical treatment of scoliosis. The objective of this study was to propose a method to analyze the three-dimensional forces acting at the rod using the changes of implant rod geometry before and after the surgical treatment. METHODS: An inverse method based on Finite Element Analysis is proposed. The geometries of implant rod before and after the surgical treatment were measured three dimensionally. The implant rod before the surgical treatment was reconstructed using an elasto plastic finite element model. The three-dimensional forces were applied iteratively to the rod through the screws such that the rod is deformed the same after the surgical treatment of scoliosis. FINDINGS: The maximum force acting at the screw of each patient ranged from 198N to 439N. The magnitude of forces was clinically acceptable. The maximum forces occurred at the lowest fixation level of vertebra of each patient. INTERPRETATION: The three-dimensional forces distribution that deformed the rod can be evaluated using the changes of implant geometry. Although the current clinical cases are still few, this study demonstrated the feasibility of measuring the forces that deformed the implant rod after the surgical treatment of scoliosis. PMID- 22321375 TI - A grand scale challenge: vaccine discovery for helminth control in definitive hosts. PMID- 22321377 TI - Preparation and characterization of dexamethasone-immobilized chitosan scaffold. AB - Chitosan film (CSF), 2-dimensional scaffold, was modified with dexamethasone (DEX) in the present work via amino-alcohol forming reaction between amino group of chitosan and carbonyl group of DEX. Successful immobilization was identified by ATR-FTIR spectroscopy and, the immobilized amounts were determined by weighting methods (WM) and integrated area analysis method (AM) of HPLC. For experiments of cell culture of osteogenic differentiation, our results showed that DEX immobilization has more efficiency than the other group (such as both groups of CSF and CSF with free DEX, CSF/fDEX), which was demonstrated as indicated by cell image analysis and ALP activity assay. The results show, as AD MSCs cultured on DEX-CSF, its shape of cell transformed to polygonal or cubical. The ALP activity assay indicates that of DEX-CSF increase about 3.5 folds than that of CSF's. The results suggest that immobilization of DEX can make chitosan scaffolds to induce differentiation of AD-MSCs toward osteoblastic lineage for bone tissue engineering application. PMID- 22321378 TI - Evaluation of adhesiveness of Acinetobacter sp. Tol 5 to abiotic surfaces. AB - The toluene-degrading bacterium Acinetobacter sp. Tol 5 shows a highly adhesive and autoagglutinating nature through cell surface nanofibers. In the present study, various aspects of the adhesiveness of Tol 5 cells were evaluated, namely, the association with biofilm formation, the specificity, and the effects of additives. During growth, Tol 5 and Pseudomonas aeruginosa PAO1 cells showed high capacities to form biofilms. However, resting PAO1 cells barely adhered to a polystyrene (PS) surface, while a large number of resting Tol 5 cells rapidly adhered. This implies that Tol 5 cells are intrinsically adhesive and that their initial attachment ability is quite high and distinguishable from their ability to form biofilm. This high adhesiveness of Tol 5 cells was considered to be nonspecific because the cells adhered to various material surfaces from hydrophobic plastic surfaces to hydrophilic glass and metal surfaces. However, Tol 5 cells were found not to be adhesive to Escherichia coli cells. Although Tol 5 cells were capable of interspecies interaction and coagglutination with E. coli cells, at the surface of cell clumps, E. coli cells localized, suggesting that they disturbed autoagglutination of Tol 5 cells. Tol 5 has a hydrophobic cell surface. However, the addition of nonionic surfactant Triton X-100 and bovine serum albumin increased the adhesion of Tol 5 cells to a PS surface, in contrast to previous reports of hydrophobic bacteria. The results highlighted the interesting features of adhesiveness of Tol 5 cells. PMID- 22321379 TI - Clinical utility of the Five-Factor Model of personality disorder. AB - There exists a great deal of research regarding the validity of the Five-Factor Model (FFM) of personality disorder. One of the most common objections to this model is concern regarding clinical utility. This article discusses clinical utility in terms of three fundamental components (i.e., ease of usage, communication, and treatment). In addition, a considerable number of recent empirical studies have examined whether the FFM compares well to personality disorder diagnostic categories with respect to all three components of clinical utility. The purpose of the current article is to provide a description of the implications of each component of clinical utility as it relates to the FFM and to acknowledge and address the empirical findings. PMID- 22321376 TI - Biophysics of mitosis. AB - Mitosis is the process by which eukaryotic cells organize and segregate their chromosomes in preparation for cell division. It is accomplished by a cellular machine composed largely of microtubules (MTs) and their associated proteins. This article reviews literature on mitosis from a biophysical point of view, drawing attention to the assembly and motility processes required to do this complex job with precision. Work from both the recent and the older literature is integrated into a description of relevant biological events and the experiments that probe their mechanisms. Theoretical work on specific subprocesses is also reviewed. Our goal is to provide a document that will expose biophysicists to the fascination of this quite amazing process and provide them with a good background from which they can pursue their own research interests in the subject. PMID- 22321381 TI - Higher perioperative morbidity and in-hospital mortality in patients with end stage renal disease undergoing nephrectomy for non-metastatic kidney cancer: a population-based analysis. PMID- 22321380 TI - Hydroxyethyl disulfide as an efficient metabolic assay for cell viability in vitro. AB - Cell viability assays have a variety of well known practical and technical limitations. All the available approaches have disadvantages, such as non linearity, high background and cumbersome protocols. Several commonly used tetrazolium chemicals rely upon generation of a colored formazan product formed by mitochondrial reduction of these compounds via phenazine methosulfate (PMS). However, sensitivity is inherently limited because their reduction relies on mitochondrial bioreduction and cellular transport of PMS, as well as accessibility to tetrazolium chemicals. In this study, we identify hydroxethyldisulfide (HEDS) as an inexpensive probe that can measure cellular metabolic activity without the need of PMS. In tissue culture medium, HEDS accurately quantitated metabolically active live cells in a linear manner superior to tetrazolium based and other assays. Cell toxicity produced by chemotherapeutics (cisplatin, etoposide), oxidants (hydrogen peroxide, acetaminophen), toxins (phenyl arsine oxide, arsenite) or ionizing radiation was rapidly determined by the HEDS assay. We found that HEDS was superior to other commonly used assays for cell viability determinations in its solubility, membrane permeability, and intracellular conversion to a metabolic reporter that is readily transported into the extracellular medium. Our findings establish the use of HEDS in a simple, rapid and low cost assay to accurately quantify viable cells. PMID- 22321382 TI - Influence of sirolimus-loaded nanoparticles on physiological functions of native human polymorphonuclear neutrophils. AB - Sirolimus (SRL) is an immunosuppressive agent of high clinical relevance that has been associated with serious side effects. Biodegradable, SRL-loaded poly(d,l lactide) nanoparticles (SRL-PLA-NPs) are being investigated as a drug delivery system to improve drug targeting. Polymorphonuclear neutrophils (PMNs) are phagocytes for particulate xenobiotics and also important trigger cells of the primary immune response. Therefore, the effects of SRL, SRL-PLA-NPs, and plain PLA-NPs on the viability of human PMNs, their essential functions, and the secretion of relevant cytokines were determined and evaluated with respect to the intracellular concentrations assessed by liquid chromatography-mass spectrometry ultra-trace analysis. For the first time to our knowledge, incorporation of NPs into PMNs was monitored by flow cytometry using fluorescence-labeled NPs. SRL accumulated intracellularly, exceeding therapeutic blood levels by a factor of two to four. Phagocytic activity was promptly reduced but recovered within 3 hours. No other parameters of the PMNs were affected. Hence, PLA-NPs appear suitable as drug carriers for SRL, allowing for better control of drug release. FROM THE CLINICAL EDITOR: This team of authors describe the incorporation of sirolimus loaded florescent NPs into polymorphonuclear neutrophils, a process that has been monitored by flow cytometry utilizing the fluorescent properties of the polymeric NPs. SRL accumulated intracellularly, exceeding therapeutic blood levels by a factor of two to four, resulting in reduced phagocytic activity that recovered within 3 hours. PMID- 22321383 TI - N-trimethyl chitosan nanoparticle-encapsulated lactosyl-norcantharidin for liver cancer therapy with high targeting efficacy. AB - N-Trimethyl chitosan (TMC) was synthesized and used to prepare lactosyl norcantharidin TMC nanoparticles (Lac-NCTD-TMC-NPs) using an ionic cross-linkage process. Lac-NCTD-TMC-NPs with an average particle size of 120.6 +/- 1.7 nm were obtained, with an entrapment efficiency of 69.29% +/- 0.76%, and a drug-loading amount of 9.1% +/- 0.07%. The release of Lac-NCTD-TMC-NPs in vitro was investigated through a dialysis method, and its sustained effect was evident. In the human liver cancer cell line HepG2, the half-maximum inhibiting concentration (IC(50)) of TMC-encapsulated Lac-NCTD (Lac-NCTD-TMC-NPs) was only 24.2% that of free Lac-NCTD at 24 hours. Lac-NCTD induced HepG2 cell death by triggering apoptosis. In vitro cellular uptake and in vivo NIR fluorescence real-time imaging both indicated a high targeting efficacy. In comparison with Lac-NCTD and Lac-NCTD chitosan NPs (Lac-NCTD-CS-NPs ), Lac-NCTD-TMC-NPs had the strongest antitumor activity on the murine hepatocarcinoma 22 subcutaneous model. FROM THE CLINICAL EDITOR: In this article the preparation of N-trimethyl chitosan encapsulated lactosyl-norcantharidin nanoparticles is described that displayed efficient targeting and sustained release in a hepatocarcinoma SC murine model. PMID- 22321384 TI - A nanoscale drug delivery carrier using nucleic acid aptamers for extended release of therapeutic. AB - We have synthesized, characterized, and optimized a novel nano drug-delivery carrier that utilizes the versatile properties of nucleic acid for programmable and on-demand drug release. The drug-delivery carrier consists of 15 nm gold nanoparticles (AuNPs) functionalized with drug binding DNA aptamers via single stranded (ss) anchor DNA. The presence of anchor DNA makes the nanocarrier flexible to be reprogrammed with various aptamers. Under the optimum binding conditions (0.4 M NaCl and 4 MUM DNA), a maximum of 101 +/- 8 anchor DNA strands were conjugated per particle. On binding DNA-aptamer:drug complexes to AuNPs, a maximum of 35 neomycin molecules were bound per AuNP. Controlled and extended release of drug from the synthesized carrier was obtained by temperature and affinity modulations. Furthermore, for the first time, we demonstrated that neomycin could bind to DNA with very high affinity (K(d) = 98.101 nM). This DNA based nanocarrier, designed using the principles of molecular biology, is expected to impact a number of treatment strategies. FROM THE CLINICAL EDITOR: In this basic science work, the authors demonstrate the feasibility of utilizing a novel nano drug-delivery carrier with the versatile properties of nucleic acid for programmable and on-demand drug release. PMID- 22321385 TI - Diterpenoids and triterpenoids with potential anti-inflammatory activity from the leaves of Aglaia odorata. AB - Chemical investigation of the leaves of the oriental medicinal plant Aglaia odorata resulted in the isolation of five compounds: two dolabellane diterpenoids, two dammarane triterpenoids and a protostane triterpenoid, along with twenty known compounds. Their structures were elucidated on the basis of extensive spectroscopic analysis and by comparison of their NMR spectroscopic data with those reported in the literature. The anti-inflammatory activities of all compounds were evaluated as inhibitory activities against lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 cell lines. Eleven compounds possessed potent nitric oxide inhibitory activity with IC(50) values ranging from 2.1 to 14.2 MUM, these being better than that of the positive control, indomethacin (IC(50)=14.5 MUM). In addition, three compounds exhibited significant activity against PGE(2) release with IC(50) values of 2.6, 16.1 and 23.0 MUM. PMID- 22321386 TI - Prenylated cinnamate and stilbenes from Kangaroo Island propolis and their antioxidant activity. AB - A prenylated cinnamic acid derivative as well as six prenylated tetrahydroxystilbenes were isolated from the ethyl acetate extract of propolis that originated from Kangaroo Island, Australia. Furthermore, six known stilbenes and two known flavanones were also identified from the same sample. Stilbenes are not common in propolis; therefore, Kangaroo Island propolis is considered a unique type of propolis that is rich in prenylated stilbenes. Stilbene propolis from Kangaroo Island showed a stronger scavenging activity towards DPPH free radical than Brazilian green propolis. This strong activity can be explained by the presence of large number of stilbenes, most of them showed strong free radical scavenging activity. PMID- 22321387 TI - HLA molecules and nasal carriage of Staphylococcus aureus isolated from dialysis and kidney transplant patients at a hospital in Southern Brazil. AB - BACKGROUND: Healthy individuals can host Staphylococcus aureus in the nasopharynx, body surface and vagina. Most invasive infections by this bacterium are endogenous, caused by strains spread from the nasopharynx of carriers. S. aureus is a pathogen involved in the etiology of hospital- and community-acquired infections. Transplant and dialysis patients are at risk of colonization or infection by multi-resistant S. aureus. Infection is directly linked to individual immunity, and the major histocompatibility complex (MHC) plays a crucial role in determining susceptibility to diseases. Different MHC specificities have been shown to be more frequent in individuals suffering from certain diseases. This study aimed to investigate the association between HLA class I (HLA-A and -B) and class II (HLA-DRB1) molecules and nasal carriage of S. aureus in dialysis and kidney transplant patients at a hospital in Southern Brazil. RESULTS: The sample consisted of 70 dialysis and 46 kidney transplant patients, totaling 116 patients. All subjects were typed for HLA molecules using LABType(r) SSO (One Lambda). Nasal swab samples of S. aureus were isolated from the nasal cavity (both nostrils) of patients undergoing dialysis or kidney transplantation.In renal dialysis patients, HLA-A*02 was the most frequent allele in both carriers (25.5%) and non-carriers (21.2%) of S. aureus. Allele A*68 was not observed in the carrier group, but the allele was observed six times in the non-carrier group (p = 0.0097). Regarding HLA-B and HLA-DRB1, no allele was shown to be involved in protection against or susceptibility to carriage of S. aureus. In kidney transplant patients, allele A*03 was more frequent in the non-carrier (20.83%) than in the carrier (5.88%) group (p = 0.0486). HLA-B*15 was present in carriers (5.88%) and non-carriers (25%) (p = 0.0179). Regarding class II alleles, DRB1*03 appeared to be related to susceptibility to carriage of S. aureus (p = 0.0319). CONCLUSIONS: Our findings suggest that HLA-DRB1*03 may be involved in susceptibility to nasal carriage of S. aureus in transplant patients. In addition, HLA-A*68 (dialysis patients) and HLA-A*03 and HLA-B*15 (transplant patients) appear to be associated with increased resistance to S. aureus nasal carriage. PMID- 22321388 TI - Effects of vaginal prolapse surgery on sexuality in women and men; results from a RCT on repair with and without mesh. AB - INTRODUCTION: In pelvic organ prolapse (POP) repair, the use of synthetic mesh is not only increasing but also a subject of discussion. The focus shifts from anatomical toward functional outcome, with sexual function being an important parameter. One of the concerns with mesh usage in POP surgery is the possible negative effect on sexual function. AIM: To compare and assess sexual function in women and men after primary cystocele repair with or without trocar-guided transobturator mesh. METHODS: One hundred twenty-five women with a symptomatic cystocele stage >= II were included in this multicenter randomized controlled trial and assessed at baseline and 6-month follow-up. MAIN OUTCOME MEASURES: Female sexual function was measured by the Female Sexual Function Index (FSFI) and male sexual function by the Male Sexual Health Questionnaire. A subgroup analysis of women with a participating partner was performed. RESULTS: In the mesh group, 54/59 women vs. 53/62 in the anterior colporrhaphy group participated. In men, 29 vs. 30 participated. After surgery, FSFI scores were comparable for both treatment groups. However, within group analysis showed significant improvement on the domains pain (effect size = 0.5), lubrication (effect size = 0.4), and overall satisfaction (effect size = 0.5) in the colporrhaphy group. This improvement was not observed in the mesh group. A subgroup of women with a participating partner reported significantly higher baseline domain scores as compared with other women and did not report a significant improvement of sexual functioning irrespective of treatment allocation. Worsening of baseline sexual function was reported by 43% of women in the mesh group compared with 18% in anterior colporrhaphy group (P = 0.05). Male sexual functioning did not change in either group. CONCLUSIONS: Women after an anterior colporrhaphy report a significant and clinically relevant improvement of their sexual functioning, whereas women after a mesh procedure did not. PMID- 22321389 TI - Chondral fragment of the lateral femoral trochlea of the knee in adolescents. AB - Most injuries to the osteochondral region in adolescents have generally been believed to occur as osteochondral fractures. However, we report three cases of pure chondral fragments of the knee in adolescents. The patients were injured during sports activities and as a result had acute limitation of ROM of the knee joint. Only one case out of three could be diagnosed by MRI, and arthroscopic examinations were needed to make a final diagnosis in the remaining two cases. Re fixation of the fragments was performed using bio-absorbable pins. All the patients were eventually able to return to their previous level of sports activity. Two years after the operation they experienced no symptoms and MRI showed that the re-fixed fragments were continuous to the bed without any abnormal intervening signal area, suggesting successful healing. Moreover, the arthroscopic integration between the re-fixed fragment and the surrounding articular cartilage was acceptable. Chondral fragment of the lateral femoral trochlea in active adolescents should be recognized as a clear entity that can be successfully treated by re-fixation. PMID- 22321390 TI - A case study of arithmetic facts dyscalculia caused by a hypersensitivity-to interference in memory. AB - While the heterogeneity of developmental dyscalculia is increasingly recognized, the different profiles have not yet been clearly established. Among the features underpinning types of developmental dyscalculia suggested in the literature, an impairment in arithmetic fact retrieval is particularly prominent. In this paper, we present a case study of an adult woman (DB) with very good cognitive capacities suffering from a specific and developmental arithmetic fact retrieval deficit. We test the main hypotheses about developmental dyscalculia derived from literature. We first explore the influential hypothesis of an approximate number system deficit, through estimation tasks, comparison tasks and a priming comparison task. Secondly, we evaluate whether DB's mathematical deficiencies are caused by a rote verbal memory deficit, using tasks involving completion of expressions, and reciting automatic series such as the alphabet and the months of the year. Alternatively, taking into account the extreme similarity of the arithmetic facts, we propose that a heightened sensitivity to interference could have prevented DB from memorizing the arithmetic facts. The pattern of DB's results on different tasks supports this hypothesis. Our findings identify a new etiology of a specific impairment of arithmetic facts storage, namely a hypersensitivity-to-interference. PMID- 22321391 TI - Stereotypes of mental disorders differ in competence and warmth. AB - Theoretical models of public stigma toward mental illness have focused on factors that perpetuate stigma toward the general label of "mental illness" or toward a handful of specific illnesses, used more or less interchangeably. The current work used the Stereotype Content Model (Fiske, Cuddy, Glick, & Xu, 2002) to examine how one facet of public stigma--stereotype content--differs as a function of specific mental illnesses. Participants were recruited online from across the U.S. Study 1 demonstrated that the overarching category of people with mental illness was perceived as relatively incompetent, but not very hostile (i.e., relatively warm). Study 2 found that when the general label of mental illness was separated into thirteen individual disorders, distinct stereotype content toward four clusters of illnesses emerged. One cluster, typified by illnesses with psychotic features (e.g., schizophrenia), was perceived to be hostile and incompetent. A second cluster, comprised of mood and anxiety disorders, was perceived as average on both competence and warmth. A third cluster of illnesses with neuro-cognitive deficits was thought to be warm but incompetent. The fourth cluster included groups with sociopathic tendencies and was viewed as hostile but relatively competent. The results clearly demonstrate that the stereotype content that underlies public stigma toward individual mental illnesses is not the same for all disorders. Harnessing knowledge of differing stereotype content toward clusters of mental illnesses may improve the efficacy of interventions to counteract public stigma. PMID- 22321392 TI - Health insurance and health-seeking behavior: evidence from a randomized community-based insurance rollout in rural Burkina Faso. AB - In 2004, a community-based health insurance (CBI) scheme was introduced in Nouna district, Burkina Faso, with the primary objective of improving access to facility-based health services. In order to overcome self-selection issues in the analysis of the behavioral effects of insurance, we combine four waves of the Nouna Health District Household Survey into a panel data set, and use the randomized timing of insurance rollout to estimate the causal effect of insurance coverage on health-seeking behavior. While we find a generally positive association between CBI affiliation and treatment seeking, we cannot reject the null that the introduction of health insurance does not have any effect on treatment seeking in general, and utilization of facility-based professional care, in particular. Low levels of health care provider satisfaction, poor perceived quality of care by enrollees, and ambiguity in the coverage level of the CBI benefit package appear to have contributed to these weak results. Our findings imply that the basic notion of insurance mechanically increasing facility-based professional care is not necessarily true empirically, and likely contingent on a large number of contextual factors affecting health-seeking behavior within households and communities. PMID- 22321393 TI - Dietary restriction increases site-specific histone H3 acetylation in rat liver: possible modulation by sirtuins. AB - We studied dietary restriction (DR) related changes of site-specific acetylation of histone H3 in rat livers to explore a possible link to histone modifications and sirtuin levels with anti-aging effects of DR. The acetylation at lysine residue 9, 27 and 56 in H3 was 20-30% higher in DR animals compared with ad libitum fed counterparts. SIRT6, one of histone deacetylases, was significantly decreased by DR and thereby may be involved in an increase in the histone acetylation. Our findings suggest that upregulation of chromatin activities through increased histone acetylation is a mechanism of anti-aging effects of DR. PMID- 22321394 TI - Restoration of muscle fibers and satellite cells after isogenic MSC transplantation with microdystrophin gene delivery. AB - Duchenne muscular dystrophy is the most prevalent inheritable muscle disease. Transplantation of autologous stem cells with gene direction is an ideal therapeutic approach for the disease. The current study aimed to investigate the restoration of myofibers in mdx mice after mdx bone marrow-derived mesenchymal stem cell (mMSC) transplantation with human microdystrophin delivery. Possible mechanisms of action were also studied. In our research, mMSCs were successfully transduced by retrovirus carrying a functional human microdystrophin gene. Transplantation of transduced mMSCs enabled persistent dystrophin restoration in the skeletal muscle of mdx mice up to the 12th week after transplantation. Simultaneous coexpression of human microdystrophin and desmin showed that implanted mMSCs are capable of long-term survival as muscle satellite cells. PMID- 22321395 TI - Crystal structure of inactive form of Rab3B. AB - Rab proteins are the largest family of ras-related GTPases in eukaryotic cells. They act as directional molecular switches at membrane trafficking, including vesicle budding, cargo sorting, transport, tethering, and fusion. Here, we generated and crystallized the Rab3B:GDP complex. The structure of the complex was solved to 1.9A resolution and the structural base comparison with other Rab3 members provides a structural basis for the GDP/GTP switch in controlling the activity of small GTPase. The comparison of charge distribution among the members of Rab3 also indicates their different roles in vesicular trafficking. PMID- 22321396 TI - Calcitonin receptor-like receptor (CLR) influences posttranslational events of receptor activity-modifying proteins (RAMPs). AB - Adrenomedullins (AM) form a multifunctional subfamily of the calcitonin gene related peptide (CGRP) superfamily, the members of which exert their physiological roles through a 1:1 combination of calcitonin receptor-like receptors (CLRs) and receptor activity-modifying proteins (RAMPs). It has been shown that RAMPs can modify the biochemical properties of CLRs; for example, RAMP escorts CLR to the plasma membrane, affects glycosylation state of CLR, and transforms the ligand selectivity of CLR, but on the other hand the effects of CLRs on the biochemical and functional properties of the partner RAMPs are not well established. In this study, using pufferfish (mefugu, mf) homolog, we revealed that mfCLR1 could affect the post-translational modification and trafficking pathway of mfRAMP1. In addition, mfCLRs boosted mfRAMP1, mfRAMP2b, and mfRAMP3 translocation to cell surface. We further revealed that mfRAMPs, except mfRAMP1 and mfRAMP3, could be expressed as multimers on the plasma membrane. However, only monomeric form of mfRAMP2a, mfRAMP4, and mfRAMP5 could heteromerize with mfCLR1 but not with mfCLR2 or mfCLR3, which was consistent with their abilities to induce cAMP response. Collectively our results indicate that the glycosylation, subcellular trafficking, and pharmacological properties of the components of RAMP-CLR receptor complexes are regulated in an interdependent manner. PMID- 22321397 TI - Biodistribution and stability of CdSe core quantum dots in mouse digestive tract following per os administration: advantages of double polymer/silica coated nanocrystals. AB - CdSe-core, ZnS-capped semiconductor quantum dots (QDs) are of great potential for biomedical applications. However, applications in the gastrointestinal tract for in vivo imaging and therapeutic purposes are hampered by their sensitivity to acidic environments and potential toxicity. Here we report the use of coatings with a combination of polythiol ligands and silica shell (QDs PolyT-APS) to stabilize QDs fluorescence under acidic conditions. We demonstrated the stability of water-soluble QDs PolyT-APS both in vitro, in strong acidic solutions, and in vivo. The biodistribution, stability and photoluminescence properties of QDs in the gastrointestinal tract of mice after per os administration were assessed. We demonstrated that QDs coated with current traditional materials - mercapto compounds (QDs MPA) and pendant thiol group (QDs PolyT) - are not capable of protecting QDs from chemically induced degradation and surface modification. Polythiol ligands and silica shell quantum dots (QDs PolyT-APS) are suitable for biological and biomedical applications in the gastrointestinal tract. PMID- 22321398 TI - Engineering fibrotic tissue in pancreatic cancer: a novel three-dimensional model to investigate nanoparticle delivery. AB - Pancreatic cancer contains both fibrotic tissue and tumor cells with embedded vasculature. Therefore anti-cancer nanoparticles need to extravasate from tumor vasculature and permeate thick fibrotic tissue to target tumor cells. To date, permeation of drugs has been investigated in vitro using monolayer models. Since three-dimensional migration of nanoparticles cannot be analyzed in a monolayer model, we established a novel, three-dimensional, multilayered, in vitro model of tumor fibrotic tissue, using our hierarchical cell manipulation technique with K643f fibroblasts derived from a murine pancreatic tumor model. NIH3T3 normal fibroblasts were used in comparison. We analyzed the size-dependent effect of nanoparticles on permeation in this experimental model using fluorescent dextran molecules of different molecular weights. The system revealed permeation decreased as number of layers of cultured cells increased, or as molecule size increased. Furthermore, we showed changes in permeation depended on the source of the fibroblasts. Observations of this sort cannot be made in conventional monolayer culture systems. Thus our novel technique provides a promising in vitro means to investigate permeation of nanoparticles in fibrotic tissue, when both type and number of fibroblasts can be regulated. PMID- 22321399 TI - Many of the challenges that we faced in 2011 will continue to transform our healthcare delivery. PMID- 22321400 TI - Diagnosing PAD by calculating the ankle brachial index: adherence to the guidelines. PMID- 22321401 TI - Experiences of living with intermittent claudication. AB - Intermittent claudication is a symptom caused by peripheral arterial disease (PAD) and is associated with pain, impaired mobility and loss of control. Walking ability is reduced due to the pain, and both physical and social functions are often negatively affected, which may lead to patients feeling they are a burden to others. An interview study using a qualitative descriptive design to describe experiences of living with intermittent claudication caused by PAD was carried out during Winter and Spring 2009/2010. Fifteen people suffering from intermittent claudication were interviewed, and the interviews were analyzed using qualitative thematic analysis. Intermittent claudication greatly affects daily living. Six themes were identified: "Experiencing discomfort in the legs," "Moving around in a new way," "Feeling inconvenient when forced to stop," "Missing previous life," "Incorporating intermittent claudication in daily life," and "To lead a strenuous life." The main theme was "Adjusting to a restricted life." The findings show that intermittent claudication has a major impact on daily life. Apart from the severity of symptoms, how the illness is experienced differs among patients, depending on how active the ill person is or wants to be. These findings suggest that increased knowledge about living with intermittent claudication is important to understand the effects on the ill person's life, as a complement to physical examinations when planning individual treatment. PMID- 22321402 TI - Use of a three-curved rocker sole shoe modification to improve intermittent claudication calf pain--a pilot study. AB - This was a pilot study utilizing hospital-based walking trials to compare two footwear conditions. Two pairs of identical therapeutic shoes were ordered for volunteer claudicant subjects. One pair was adapted with a specifically designed three-curve rocker sole. Volunteer claudicant subjects (n = 8, mean age 66 +/- 9.9 years) with stable pain-free distances of 10-400 meters to calf claudication pain were recruited into the study. Walking trials were used to compare differences in both the pain-free distance to claudication and the intensity of the calf pain once claudicating exhibited by each subject while walking separately with the two footwear conditions during the same clinical session. The results demonstrated that claudicant pain-free walking distance was increased, and the intensity of claudication calf pain reduced when walking with the rocker soled in comparison with baseline. A specifically designed rocker sole has the potential to offer a reduction in the intensity of calf pain experienced by claudicants. A more extensive study is planned to determine the efficacy of this new footwear adaptation when the footwear is worn for extended periods. PMID- 22321403 TI - Sympathetic cardiac modulation and vascular worsening in arteritis: a case report. AB - Increases in sympathetic modulation have been associated with increased risk of acute cardiovascular events in some populations. However, whether altered cardiac autonomic modulation is related to peripheral vascular worsening has not yet been described. In this study, we assessed cardiac autonomic modulation by heart rate variability in two patients with arteritis who were followed up for 5 months. Only the subject who presented high cardiac sympathetic modulation had acute vascular worsening. This case report suggests that cardiac autonomic modulation may be related to vascular worsening in patients with arteritis. PMID- 22321404 TI - Quality of care of vascular access in hemodialysis patients in a hemodialysis center in Iran. AB - Because of the lack of study in the field of vascular access care for hemodialysis patients, an observational study was conducted on 110 patients undergoing chronic hemodialysis in the Isfahan's AliAsghar Hospital. Data were collected using a demographic questionnaire and a checklist related to vascular access care techniques. A total of 63 male and 47 female with an average of 40.02 months of hemodialysis were studied. In addition, 72 patients were under hemodialysis through arteriovenous fistula and 38 patients through subclavian catheters. The overall quality of care for vascular access site was moderate. Selecting an inappropriately high speed for the apparatus at the beginning of dialysis, needling of an aneurysm or needling near the fistula, and incomplete priming of the filter and the tubes were the most frequent inappropriate actions. Reinforcement of the nurses' continuing education programs and development of standard vascular access care protocols are recommended. PMID- 22321405 TI - Review of an article: Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial. Jill J.F. Belch, MD, FRCP, John Dormandy, MD, FRCS, and the CASPAR Writing Committee, Dundee and London, United Kingdom (J Vasc Surg 2010;52:825-33). PMID- 22321406 TI - Anti-tuberculosis prophylaxis following renal transplantation: acceptable variations? AB - BACKGROUND: Guidelines suggest tuberculosis (TB) prophylaxis in renal transplant recipients originating in endemic areas or in those at risk from non-endemic countries. Concern remains that these guidelines may fail to provide adequate prophylaxis for a cohort of patients who remain at potential risk. We aimed to determine variation patterns among different transplant units within the United Kingdom (UK) with regard to TB prophylaxis policy. METHODS: The renal pharmacist at each of the 25 UK renal transplant centers was contacted. Specific information was obtained relating to drug prophylaxis given, duration of treatment, as well as which transplant recipients were eligible for treatment. RESULTS: A 96% response rate (24/25 centers) was achieved. Prophylaxis regimens varied from no prophylaxis to isoniazid 300 mg given life-long. The most common duration of treatment was 6 months post transplantation (at 7 centers). Variations existed in the concurrent use of pyridoxine. A wide discrepancy was seen in the determination of who should receive prophylaxis, with no clear association with frequency of TB incidence in the region. CONCLUSIONS: A marked discrepancy exists among national renal transplant units in pharmacologic prophylaxis for TB, as well in the selection of individuals for this treatment. PMID- 22321407 TI - Determination of geniposidic acid in rat plasma by LC-MS/MS and its application to in vivo pharmacokinetic studies. AB - A simple, rapid and sensitive method for the determination of geniposidic acid (GSA) in rat plasma was developed using liquid chromatography tandem mass spectrometry (LC-MS/MS). Geniposide (GS) was used as the internal standard. Rat plasma pretreated by solid-phase extraction (SPE) was analyzed by LC-MS/MS with negative ion mode electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. The analytical column was C8 column and the mobile phase was methanol (A) and water (B). The flow rate was set at 0.8 mL/min with split ratio of 1:3, the total run time was 15 min. The MS/MS ion transitions monitored were m/z 373.3-211.1 for GSA and m/z 387.3-225.3 for GS. The quantification limit was 5 ng/mL within a linear range of 10-4000 ng/mL. The inter-day and intra-day accuracy and precision were within +/-10%. The method was fully validated for its sensitivity, selectivity, matrix effect, stability study and recovery. The data indicate that our LC-MS/MS assay is an effective method for the pharmacokinetics study of GSA in rat plasma. PMID- 22321408 TI - Development and validation of an LC-ESI-MS/MS method for the determination of nitidine chloride in rat plasma. AB - A new liquid chromatography-electrospray ionization-mass/mass spectrometry (LC ESI-MS/MS) assay method has been developed and validated for the quantification of nitidine chloride (NC), an anti-cancer bioactive substance of Zanthoxylum nitidum (Roxb.) DC. plants, in rat plasma using carbamazepine as an internal standard (I.S.). The NC and I.S. were extracted from rat plasma by acetonitrile protein procedure. Chromatographic separation was carried out with a C(18) column (2.1 mm * 150 mm, 3 MUm) with a security guard C18 column (4 mm * 20 mm, 3 MUm). The mobile phase consisted of acetonitrile-10 mM ammonium acetate buffer solution formic acid (35:65:0.2, v/v/v) and delivered at the flow rate of 0.25 mL/min. LC ESI-MS/MS was performed on a triple-quadrupole mass spectrometry equipped with electrospray ionization (ESI) and positive multiple reaction monitoring (MRM). Target ions were monitored at [M](+)m/z 348.2 for NC and [M]+ m/z 237.2 for I.S. The method was linear over the concentration range of 5.0-1500.0 ng/mL. The intra and inter-day relative standard deviations of the assay were less than 5.0%. The lower limit of quantification was 5.0 ng/mL. The developed method was successfully applied to the estimation of the pharmacokinetic parameters of NC by intravenous administration to rats. PMID- 22321409 TI - Revealing multi-binding sites for taspine to VEGFR-2 by cell membrane chromatography zonal elution. AB - A new high-expression vascular endothelial growth factor receptor-2 (VEGFR-2) cell membrane chromatography (CMC) method was developed to investigate the affinity of ligands for VEGFR-2. An HEK293 VEGFR-2/CMC system was applied to specifically recognize ligands acting on VEGFR-2. Sorafenib was used as a mobile phase additive to evaluate the effect of the marker's concentration on the retention of sorafenib and taspine, respectively. The relationship among the retention, the types of binding sites and the affinity of taspine binding to VEGFR-2 has also been concerned. The retention behavior indicated that sorafenib had two major binding regions on VEGFR-2, and that taspine might act as a multi target VEGFR-2 inhibitor with similar biological activity to sorafenib. The equilibrium dissociation constants (K(D)) obtained from the model are (5.25 +/- 0.31) * 10-7 and (9.88 +/- 0.54) * 10-5 mol L-1 for sorafenib at the high- and low-affinity sites, respectively, and the corresponding values for taspine are (3.88 +/- 0.31) * 10-6 and (7.04 +/- 0.49)*10-5 mol L-1. The two types of binding sites contributed about a 1:2 ratio on the retention of taspine. PMID- 22321410 TI - On-line continuous sampling dynamic microwave-assisted extraction coupled with high performance liquid chromatographic separation for the determination of lignans in Wuweizi and naphthoquinones in Zicao. AB - The on-line continuous sampling dynamic microwave-assisted extraction (on-line CSDMAE) coupled with high-performance liquid chromatographic separation and determination of the lignans in Wuweizi and naphthoquinones in Zicao was developed. The extraction, separation and determination of target analytes were simultaneously carried out. The experimental parameters, including type of extraction solvent, microwave extraction power, solvent flow rate, amount of sample and particle size of the sample, were evaluated by the univariate method and orthogonal screening. The detection limits for schisandrin A, schisantherin A, deoxyschizandrin, shikonin and beta,beta'-dimethylacrylshikonin are 0.86, 0.90, 0.27, 0.42 and 0.92 MUg mL-1, respectively. Compared with the conventional extraction methods, such as off-line continuous microwave-assisted extraction, ultrasound-assisted extraction and Soxhlet extraction, the proposed method is quicker and more effective. PMID- 22321411 TI - Persistence of fipronil and its risk assessment on cabbage, Brassica oleracea var. capitata L. AB - Persistence of fipronil in cabbage was studied following three applications of Jump 80 WG at 75 and 150 g a.i. ha(-1) at 7 day interval. The average initial deposits of total fipronil (fipronil and its metabolites) were 1.226 and 2.704 mg kg(-1) on the heads following 3rd application of fipronil at single and double the dosages, respectively. Desulfinyl was found to be the main metabolite followed by sulfone and sulfide. Metabolite amide was not detected in cabbage samples. Half-life periods for fipronil were found to be 3.43 and 3.21 day at single and double the application rates, respectively. Risk assessment of fipronil to the consumers was calculated on the basis of per capita 80 g consumption of cabbage and comparing it to its ADI for an adult of 55 kg which was found to be less than its ADI on 10th day at both the dosages. PMID- 22321412 TI - Interpretation of honeybees contact toxicity associated to acetylcholinesterase inhibitors. AB - The widespread use of different pesticides generates adverse effects on non target organisms like honeybees. Organophosphorous and carbamates kill honeybees through the inactivation of acetylcholinesterase (AChE), thereby interfering with nerve signaling and function. For this class of pesticides, it is fundamental to understand the relationship between their structures and the contact toxicity for honeybees. A Quantitative Structure-Activity Relationship (QSAR) study was carried out on 45 derivatives by a genetic algorithm approach starting from more than 2500 descriptors. In parallel, a new 3D model of AChE associated to honeybees was defined. Physicochemical properties of the receptor and docking studies of the derivatives allow understanding the meaningful of three descriptors and the implication of several amino acids in the overall toxicity of the pesticides. PMID- 22321413 TI - H1N1 influenza A virus neuraminidase modulates infectivity in mice. AB - In the 2years since the onset of the H1N1 2009 pandemic virus (H1N1pdm09), sporadic cases of oseltamivir-resistant viruses have been reported. We investigated the impact of oseltamivir-resistant neuraminidase from H1N1 Brisbane like (seasonal) and H1N1pdm09 viruses on viral pathogenicity in mice. Reassortant viruses with the neuraminidase from seasonal H1N1 virus were obtained by co infection of a H1N1pdm09 virus and an oseltamivir-resistant H1N1 Brisbane-like virus. Oseltamivir-resistant H1N1pdm09 viruses were also isolated from patients. After biochemical characterization, the pathogenicity of these viruses was assessed in a murine model. We confirmed a higher infectivity, in mice, of the H1N1pdm09 virus compared to seasonal viruses. Surprisingly, the oseltamivir resistant H1N1pdm09 virus was more infectious than its sensitive counterpart. Moreover, the association of H1N1pdm09 hemagglutinin and an oseltamivir-resistant neuraminidase improved the infectivity of reassortant viruses in mice, regardless of the NA origin: seasonal (Brisbane-like) or pandemic strain. This study highlights the need to closely monitor the emergence of oseltamivir-resistant viruses. PMID- 22321414 TI - [Development of nasal-orbital surgery]. PMID- 22321415 TI - [Clinical effect of orbit fracture reconstruction under nasal endoscope]. AB - OBJECTIVE: To investigate the clinical effect of orbit blowout fracture reconstruction under nasal endoscope. METHODS: Forty-one cases of orbit fracture were reconstructed for lost or damaged orbit under nasal endoscope through maxillary sinus, ethmoidal sinus or the both. RESULTS: Among the 35 cases of orbit blowout fracture, enophthalmos in 33 cases were completely improved, 29 cases were symmetrical to normal eye after operation without diplopia except that 6 cases had slight enophthalmos accompanied with slight diplopia. Among these 6 cases, 4 cases returned to normal without diplopia 6 months after operation. In the 6 cases of orbit non-blowout fracture, 4 cases were symmetrical to normal eye after operation without enophthalmos, diplopia and facial malformation. One case had slight enophthalmos and diplopia, 1 case had slight enophthalmos with slight facial malformation. CONCLUSIONS: The surgery under nasal endoscope is safe and credible. The method can be easily mastered and its complication is less. PMID- 22321416 TI - [Clinical research on nasal endoscopic surgery for rhinogenous optic function damage]. AB - OBJECTIVE: To explore the surgical treatment of rhinogenous optic function damage (ROFD) through transnasal endoscopic approach. METHODS: Twenty-three patients (25 eyes) with ROFD were retrospectively reviewed. All patients were operated on through transnasal endoscopic approach, and 9 patients underwent endoscopic optic nerve decompression. RESULTS: Four patients had bilateral pansinusitis, 6 patients had unilateral posterior ethmoidal sinusitis and sphenoiditis. One patient had frontal and ethmoidal sinusitis. Five patients had fungal sinusitis occurred in the sphenoid sinus and unilateral posterior ethmoid sinus. Two patients had unilateral pyocyst and cyst of the sphenoid and ethmoid sinus. The preoperative visual acuity preoperative were as follows: 2 patients (2 eyes) no light perception (NLP), 6 patients (7 eyes) hand movement (HM), 7 patients (7 eyes) fingers counting (FC) less than 20 cm and 8 patients (9 eyes) were vision impaired in different degree. One patient (1 eye) was ophthalmoptosis, direct and indirect light reflex vanished. Three patients (3 eyes) diplopia, 2 patients (2 eyes) abduction paralysis, 3 patients (3 eyes) defect of visual field. One patient ptosis of upper lid. The visual acuity postoperative: 2 eyes failed, 10 eyes cured;13 eyes improved from HM or FC to FC (30-60 cm). CONCLUSIONS: The endoscopic sinus surgery combined with appropriate medical therapy are effective to ROFD. Patients who suffered from severe visual damage and either unresponsive or intolerant to medical treatment should be administrated endoscopic sinus surgery including endoscopic optic nerve decompression. PMID- 22321417 TI - [Endoscopic trans-ethmoid medial orbital wall decompression combined with intraconal fat decompression for Graves' ophthalmopathy]. AB - OBJECTIVE: To present a new mini-invasive surgery for compressive optic neuropathy (CON) in Graves' ophthalmopathy (GO) by adequately decompressing the orbital apex and correcting proptosis, and to analyze its results. METHODS: A retrospective chart was reviewed in 29 patients receiving orbital decompression for the treatment of CON secondary to GO from October 2006 to May 2011. All patients diagnosed CON were in stable and inactive phase of GO at least for 6 months. All patients received endoscopic transethmoid medial orbital wall decompression to reduce the compression on the orbital apex. In the meanwhile, an endoscopic transethmoid intraconal fat-removal orbital decompression was performed to remove parts of intraconal fat with a special aspiration/cutting instrument to further reduce the proptosis. All patients were followed up periodically. RESULTS: of improvement of visual acuity (VA), color vision, and amount of proptosis reduction and incidence of induced diplopia 9 months after surgery was recorded for analysis its feasibility. RESULTS: Forty-five orbits of 29 patients were included in the study. At the 9 months review, 44 of 45 eyes (97.8%) improved their VA from -0.65+/-0.30 (x+/-s) preoperatively to -0.24+/ 0.22, with a mean improvement of 0.55+/-0.17 (t=-13.012, P<0.001), 23 of 29 eyes (79.3%) had improved color vision (P<0.001), and the mean reduction in proptosis was (7.07+/-1.59) mm (range 4-11 mm). Postoperative symmetry to within 2 mm were achieved in all patients. Except 1 patient complaining of deterioration in diplopia following surgery, no patients presented new on-set diplopia postoperatively. CONCLUSION: The endoscopic transethmoid medial orbital wall decompression combined with the endoscopic transethmoid intraconal fat-removal orbital decompression is an effective treatment with minimal morbidity for both visional recovery and improvement of proptosis for CON in GO. PMID- 22321418 TI - [Three-dimensional fluid attenuated inversion recovery imaging at 3T MRI in sudden deafness: its findings and relationship with the prognosis]. AB - OBJECTIVE: To investigate inner ear of patients with sudden deafness with three dimensional fluid attenuated inversion recovery (3D FLAIR) MRI, and the relationship between the results of 3D FLAIR and the prognosis. METHODS: Twenty three patients with sudden deafness received 3D FLAIR at 3T MRI, and the signals of inner ear were recorded. Hearing levels were evaluated at initial visit and after treatment. The relationship between 3D FLAIR findings and hearing prognosis was evaluated. RESULTS: Eight patients with sudden deafness showed high signals in the affected cochlea on 3D FLAIR, the others of affected cochlea and all of contralateral cochlea showed no signal on 3D FLAIR. The age, sex, affected side, period to initial visit and initial audiogram had no difference between cochlea no signal group and high signal group. The average auditory threshold (x+/-s) in cochlea high signal group (90+/-21) dB HL was significant higher than that in cochlea no signal group (60+/-28) dB HL, P<0.05 at patients' discharge. After treatment, in cochlea no signal group, two cases' hearing was complete recovered, remarkable improvement in five cases, slight improvement in two cases and no change in six cases. In cochlea high signal group, hearing was slight improvement in one case and no change in seven cases. The prognosis was significant difference between two groups. Five of seven patients with vertigo and sudden deafness showed high signal in affected side vestibule on 3D FLAIR, and the hearing of whom had no change after treatment. CONCLUSION: 3D FLAIR can show high signal in affected inner ear in sudden deafness patients, and which is related to a poor hearing prognosis. PMID- 22321419 TI - [Endoscopic maxillary sinus surgery through anterior or posterior nasolacrimal duct approach]. AB - OBJECTIVE: To explore the feasibility and effectiveness of the approaches and methodology of the endoscopic surgery for maxillary sinus lesions through the medial wall of the maxillary sinus. METHODS: From Jun. 2003 to Aug. 2010, endoscopic surgery through anterior or posterior nasolacrimal duct approaches to remove maxillary sinus lesions were conducted in 139 patients. Among them there were 43 cases with inverted papilloma, 63 cases with fungal maxillary sinusitis, 28 cases with maxillary sinus cyst, 3 cases with hemorrhagic necrotic polyps, and 2 cases with osteomas. All patients underwent preoperative CT scans, and patients with inverted papillomas also had MRI tests. Anterior-nasolacrimal canal paths included 3 ways: pyriform aperture, lacrimal bone recess (dissecting nasolacrimal duct or not were 2 subtypes), pyriform aperture-nasolacrimal duct approaches, and 97 patients were treated. Posterior-nasal lacrimal duct paths were also divided into 3 subtypes: the inferior turbinate flip flap, double pedicle inferior turbinate, single pedicle inferior turbinate, and 42 patients were treated. The postoperative effects were observed. RESULTS: All lesions were completely removed under endoscope, the nasolacrimal ducts and inferior turbinates were protected, no nasal lacrimal duct injury and inferior turbinate necrosis were found. Postoperative nasal congestion, headache, swelling discomfort, strange odor, dental pain and numbness and other symptoms gradually disappeared. Nine patients felt nasal dryness, and after nasal washing for about 1 month, the symptom gradually disappeared. Patients were followed up for 6 months to 79 months. In case of osteoma, and hemorrhagic and necrotic polyps, no recurrences were found. Apparent edema, hypertrophy of sinus mucosa could be seen during the surgery in all patients with fungal maxillary sinusitis, and the edema gradually disappeared after 3 months or so, with no relapse. Two cases of maxillary sinus cysts were found in other parts of the maxillary sinus 10 months and 18 months after the surgery, but the cysts were small and asymptomatic, so no further management needed, and they were still under follow-up. Three patients, recurred. In 1 case with inverted papilloma, a local lump on the opening were found 17 months after the surgery, and was removed in out-patient department and pathology showed papillary tumor recurrence, no relapse was found 1 year later; 1 patient had recurrence in anterior ethmoid sinus 15 months after operation, total ethmoidectomy was done and no relapse was found in 3 years. One patient had local recurrence in the posterolateral wall of the maxillary sinus 26 months after operation, and the secondary surgery was done via single pedicle inferior turbinate. The papilloma relapsed again after 1 year, an endoscopic Denker surgery was performed, with no recurrence after 18 months of follow-up. Three months after surgery, the maxillary sinus was scar-covered in all cases. Inferior turbinate maintained good shape, compared to those with inferior nasal meatus windowing surgery. Scars were significantly smaller, but no latch or obstruction of drainage were found. CONCLUSIONS: Endoscopic maxillary sinus surgery through anterior or posterior nasolacrimal duct approach can reduce the trauma, fully expose the sinuses, and facilitate postoperative treatment and review with a window. Retained inferior nasal turbinate is helpful to avoid dryness, crusting, headache and other complications due to too much removal of nasal exteral walls. PMID- 22321420 TI - [Long-term treatment outcome in patients undergoing cricohyoidoepiglottopexy for glottic carcinoma]. AB - OBJECTIVE: To investigate the long-term results of cricohyoidoepiglottopexy(CHEP) in the treatment of glottic carcinoma. METHODS: A retrospective chart review of 92 consecutive patients who underwent CHEP in the selected institut from January 1990 to December 2008. Of the 92 cases, 41 cases of stage I, 39 cases of stage II, 12 cases of stage III. The time for the decannulation and the removal of the nasal feeding and quality of phonation were used for evaluating postoperative functional rehabilitation. The estimated long-term survival rates were calculated by Kaplan-Meier method. RESULTS: Among 92 patients, 26 cases (27 sides) received neck dissection and lymph nodes were pathologically positive in 3 patients (11.1%). All final surgical margins were negative for tumor invasion. Seven patients had postoperative radiotherapy and one had chemoradiation. Thirteen patients (14.1%) were found local recurrence and nine patients (9.8%) had postoperative metastases. Overall 3-, 5- and 10-year survival rates were 90.0%, 84.5% and 67.0% respectively. Cox multivariate analysis showed that the recurrence had significant influences on the overall survival rate. CONCLUSION: CHEP not only is relatively easy to master, but also effective in the treatment of glottic carcinoma. PMID- 22321421 TI - [Functional reconstruction after total or near total glossectomy]. AB - OBJECTIVE: To evaluate the functional outcomes of patients who underwent total or near total glossectomy with pectoralis major myocutaneous flap (PMMF) or free flap (FF) reconstruction. METHODS: Retrospective study of 38 consecutive patients undergoing total or near total glossectomy with PMMF or FF reconstruction. The outcomes of decannulation, feeding and speech function recovery were compared. RESULTS: Near total glossectomy was performed in 33 patients and total glossectomy was performed in 5 patients. Twenty five patients underwent reconstruction with PMMF including 2 salvage reconstructions after free flaps failure. All PMMFs survived except one complete necrosis. The success rate of PMMF was 96.0% (24/25). Fifteen patients underwent reconstruction with FF. Two flaps developed complete necrosis and the success rate of FF was 86.7% (13/15). The difference in the rates between the two groups was not significant (P=0.545). In the PMMF and FF groups, the renewal of oral feeding were 65.2% (15/23) and 100% (13/13), P<0.05, and the tracheostomy decannulation were 52.2% (12/23) and 100% (12/12), P<0.05, respectively. Postoperative feeding function recovery was better in FF group than that in PMMF group (P=0.011). Single factor analysis showed that using FF and maintaining the continuity of the mandible were related to successful rate of renewal of oral feeding. Multivariate Logistic regression analysis showed that the continuity of the mandible was the only independent predictor for renewal of oral feeding. There was no significant difference in the postoperative speech functions between the two groups. CONCLUSIONS: The continuity of the mandible is the major factor to restore the functional outcomes in feeding after total or near total glossectomy. Compared with PMMF, using FF is more beneficial to retain or rebuild the continuity of the mandible. PMID- 22321422 TI - [Comparison of lateral arm flap and radial forearm flap in reconstruction after oral cancer ablation]. AB - OBJECTIVE: To compare the clinical application of lateral arm flap and radial forearm flap in reconstruction after oral cancer ablation. METHODS: The clinical data of 21 cases with lateral arm flap and 104 cases with radial forearm flap between 2007 and 2009 were reviewed. The flap harvest time, flap survival rate, donor site morbidity and postoperative oral function were compared and analyzed. RESULTS: The average flap harvest time of lateral arm flap and radial forearm flap were (46.4+/-7.6) min and (41.5+/-7.5) min (x+/-s) respectively. The flap survival rates of the two flaps were 90.5% (19/21) and 95.2% (99/104) respectively. There was no significant difference between the two flaps in the average flap harvest time and survival rate (P>0.05). The donor site of lateral arm flap could be primarily closed and radial nerve injury occurred in 2 patients. Skin graft was necessary for the donor site closure of radial forearm flap and conspicuous unattractive scar could be seen. All patients could have oral diet and no difficulty in speech intelligibility. CONCLUSION: The lateral arm flap is relatively safe and reliable alterative to the radial forearm flap for the defects reconstruction after oral cancer ablation. PMID- 22321423 TI - [Study on discrepant protein expression in rat auditory cortex under impulse noise exposure]. AB - OBJECTIVE: Impulse noise was adopted in adult rats to built acute deafferent animal model. Differential proteomics techniques were applied to detect the changes of protein expression in the auditory cortex before and after the noise exposure. METHODS: Thirty adult SD rats were divided into three groups: normal group, rats with acute noise exposure and rats 28 days recovery after noise exposure (n=10/group). All animals were exposed to impulse noise at 156 dB for 50 pulses with a rise-time of 100 us and duration of around 0.25 ms. ABR was used to evaluate the auditory function. The two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS) were used to identified the differential protein expression. RESULTS: Compared with the normal group, ABR thresholds were found significantly increased at 2, 4, 8, 16, 32 kHz (P<0.05) in the acute and recovery groups. There was a 40-60 dBSPL ABR threshold shift at all tested frequencies immediately after impulse noise exposure. There was a partial recovery of ABR thresholds at 7 day to 28 days after impulse noise exposure. In addition, it seemed that the thresholds were rather stable and no further ABR threshold recovery was observed from 14 day to 28 days after the impulse noise exposure. Using differential proteomic techniques, 36 spots containing 27 proteins were revealed and identified in auditory cortex. Those proteins are related to cytoskeleton, neurotransmission, energy supply, mitochondrial function and synaptic remolding. CONCLUSIONS: Impulse noise may influence the function of microtubule transport and cell metabolism, there after affect the neurotransmission of auditory neurons. The compensatory changes such as pre- and postsynaptic or such related functional changes may also happen in auditory cortex after the deafferentation treatment. PMID- 22321424 TI - [Effect of sildenafil on ABR thresholds shift to noise-induced hearing loss in guinea pigs]. AB - OBJECTIVE: To investigate the protective effects of sildenafil to noise-induced hearing loss in guinea pigs. METHODS: Guinea pigs were randomly divided into control group, noise exposure group and the sildenafil treatment group, with 10 in each group. One week after the exposure of 110 dB (A) white noise, sildenafil [10 mg/(kg*d)] and normal saline [4 ml/(kg*d)] were injected into guinea pigs of noise plus sildenafil group (NSG) and noise plus normal saline group(NNG) respectively. One week after noise exposure to four weeks continuous administration. ABR thresholds were measured respectively prior to the experiment, 1 week post-noise, 1, 2 and 4 weeks post-drugs. The changes of cochlea hair cells were also observed by scanning electron microscope (SEM). RESULTS: After noise exposure, the ABR threshold shifts in NSG were significantly fewer than that in the NNG. An average of 19.1 dB in NNG compared with 19.8 dB in NSG. Four weeks after exposure, the threshold shifts were become larger to 22.0 dB in NNG while become smaller to 4.8 dB in NSG. Compared NNG with NSG, in addition to noise exposure time point, there were statistically significant differences in the rest time points after administration of the ABR threshold (P<0.05). SEM showed that the inner and outer hair cells in NNG displayed mess, fusion and imperfections. In NSG, the hair cells displayed slight pathological changes, there was no significant difference when compared with control group. CONCLUSION: Sildenafil is able to reduce the ascending of ABR thresholds shift, and it can significantly protect against noise-induced hearing loss. PMID- 22321425 TI - [CT evaluation of bone remodeling in rabbit models with rhinosinusitis]. AB - OBJECTIVE: To evaluate the findings of computed tomography (CT) as objective markers of bone remodeling in rabbit models with chronic rhinosinusitis. METHODS: Forty-eight rabbit models were established by vaccination of staphylococcus aureus. The rabbits were divided into 3 groups according to the time of infection: group A, B and C (4, 8, 12 weeks after infection), 16 rabbits in each group. Each group was subdivided into the medication administration team and the control team, 8 rabbits in each team. All the rabbits were examined by CT before vaccination to rule out the disease of nasal cavity and sinuses, and the CT images were used as the negative control. No interference was given to the control teams which were only examined again by CT when reached the end week. Dexamethasone sodium phosphate were administered to the medication administration teams 2 weeks before the end of experiment, and were examined by CT at the end. The images of both horizontal position and coronal position by reconstruction were obtained. The Hounsfield unit (Hu) of the bone which was the thickest position in each image were measured. The data was analyzed by SPSS 16.0 software. The Hu was analyzed statistically to compare the situation of the bone remodeling in different periods and administration in the rabbit models with CRS. RESULTS: Average Hu (x+/-s) of normal rabbits was 810.0+/-99.7, average Hu at the end time: control team in group A was 964.0+/-84.6, medication administration team in group A was 833.0+/-92.5; control team in group B was 987.0+/-91.5, medication administration team in group B was 886.0+/-91.6; control team in group C was 1086.0+/-74.0, medication administration team in group C was 899.8+/-76.5. The Hu in all groups were higher than normal (t value were 2.747, 4.513 and 7.350 respectively, all P<0.05). No statistical difference was found between control teams of group A and B (t=0.423, P=0.667). The Hu in control team of group C was higher than group B (t=3.905, P=0.001); There was no statistical difference between medication administration teams of group A and B (t=0.892, P=0.384), and group B and C (t=0.886, P=0.385). The Hu of all medication administration teams in 3 groups were lower than all the control teams (t value were 2.717, 3.687, 8.379 respectively, all P<0.05). CONCLUSIONS: Bone remodeling was found in rabbit models with rhinosinusitis, and the phenomenon was more obvious if the period was lengthened. The Hu could reflect the degree of bone remodelling. Glucocorticoids could depress the bone remodeling in the rabbit models with rhinosinusitis. PMID- 22321426 TI - [Effects of combining tumor necrosis factor related apoptosis-inducing ligand with PI3-K-Akt inhibition on nasopharyngeal carcinoma cell]. AB - OBJECTIVE: To study the effects of combinative therapy of tumor necrosis factor related apoptosis-inducing ligand (TRAIL) and PI3-K-Akt inhibitor on the growth and apoptosis of nasopharyngeal carcinoma (NPC) cells and underlying mechanisms. METHODS: With cell growth assay, flow cytometric analysis and Western blotting, the effects of TRAIL and PI3-K-Akt special inhibitor (LY294002) on cell growth, apoptosis and related proteins expressions in CNE-2 cell lines were studied. RESULTS: When concentrate of TRAIL>1 ng/ml, viability rate of cells in combinative treatment group with TRAIL and LY294002 was higher than that in the single treatment group with TRAIL (all P<0.05). When concentrate of TRAIL were 10 ng/ml and 100 ng/ml, the combinative treatment induced CNE-2 apoptosis more obviously than single treatments (t were 7.167 and 7.206, all P<0.05). The combination group showed more cleavage of Caspase-8, Caspase-3, Caspase-9 than single treatment groups. CONCLUSIONS: Combinative application of TRAIL and PI3-K Akt pathway inhibitor inhibits the growth of CNE-2 and induces apoptosis. The mitochondrial dependent pathway is implicated for the underlying mechanism. PMID- 22321427 TI - [Efficacy of sublingual immunotherapy with dermatophagoides farinae drops in patients with allergic rhinitis]. AB - OBJECTIVE: To evaluate the efficacy of sublingual immunotherapy (SLIT) with dermatophagoides farinae drops in patients with allergic rhinitis (AR). METHODS: Two hundred and six patients with AR aged from 4 to 60 years were included in this study. Among them, 123 patients completed more than one year treatment, the number of patients completed one year, one year and a half, two years were 61, 41, 21 cases. Rhinitis symptom scores and medication scores of the three groups before and after treatment were compared. And rhinitis symptom scores and medication scores of patients with one year drug withdrawal after one and two years treatment were aslo compared. RESULTS: After SLIT one year, one year and a half, two years treatment, the symptoms in these patients were significantly improved compared with before. The symptom scores (x+/-s) were reduced from 6.00+/-2.27, 7.39+/-1.99 and 6.29+/-2.14 to 2.95+/-1.82, 3.28+/-2.58, 2.48+/ 1.99. The differences were statistically significant (t value was 8.19, 10.29, and 5.97, all P<0.01). The proportion of patients without drug treatment of the three group were 68.9%, 73.2% and 80.9%, there was statistical significance before and after treatment in every group (value was 50.391, 43.619, 27.776, all P<0.01). Symptom improvement of sneezing, runny nose, nasal congestion, nasal itching were similar after one year, one year and a half, two years SLIT treatment, the differences were not statistically significant (F values were 1.200, 1.276 and 2.333, all P>0.05). The proportion of patients without drug treatment in the group which stopped medication one year after two year SLIT (76.2%) was higher than group stopped medication one year after one year SLIT (61.3%). There was no statistical significance (chi2=1.263, P>0.05). CONCLUSION: The dust mite drops can relieve symptoms after one year treatment, but the proposed two years treatment is important for the consolidation of improved symptoms, especially for the effect of reducing the use of symptomatic medication. PMID- 22321428 TI - [Sinonasal teratocarcinosarcoma: 2 cases report]. PMID- 22321429 TI - [Case report: peritonsillar abscess with deep cervical space and mediastinal infection]. PMID- 22321430 TI - [One case: myeloid sarcoma of the tonsil]. PMID- 22321431 TI - [Resection of laryngeal chondroma and functional reconstruction: case report]. PMID- 22321432 TI - [Progress of reservation of laryngeal function after supracricoid partial laryngectomy]. PMID- 22321434 TI - [Surgery for thyroid cancer: experience of Memorial Sloan-Kettering Cancer Center (II)]. PMID- 22321433 TI - [The rules and experiences of endoscopic surgery for common nose-eye related diseases]. PMID- 22321435 TI - First initial community-acquired meningitis due to extended-spectrum beta lactamase producing Escherichia coli complicated with multiple aortic mycotic aneurysms. AB - We report the first case of extended-spectrum beta-lactamase producing E. coli community-acquired meningitis complicated with multiple aortic mycotic aneurysms. Because of the acute aneurysm expansion with possible impending rupture on 2 abdominal CT scan, the patient underwent prompt vascular surgery and broad spectrum antibiotic therapy but he died of a hemorrhagic shock. Extended-spectrum beta-lactamase producing E. coli was identified from both blood and cerebrospinal fluid culture before vascular treatment. The present case report does not however change the guidelines of Gram negative bacteria meningitis in adults. PMID- 22321436 TI - Construction of a robust, large-scale, collaborative database for raw data in computational chemistry: the Collaborative Chemistry Database Tool (CCDBT). AB - A robust metadata database called the Collaborative Chemistry Database Tool (CCDBT) for massive amounts of computational chemistry raw data has been designed and implemented. It performs data synchronization and simultaneously extracts the metadata. Computational chemistry data in various formats from different computing sources, software packages, and users can be parsed into uniform metadata for storage in a MySQL database. Parsing is performed by a parsing pyramid, including parsers written for different levels of data types and sets created by the parser loader after loading parser engines and configurations. PMID- 22321437 TI - Ulnar to radial dorsal fracture-dislocations of the wrist: a report of 2 cases. AB - This report describes 2 patients with apparent ulnar to radial dorsal fracture dislocation: 1 had a transtriquetrum, translunate fracture dislocation and the other had a reverse stage 2 lesser arc perilunate dislocation with fracture of the ulnar styloid at its base. PMID- 22321438 TI - The reverse posterior interosseous artery flap: technical considerations in raising an easier and more reliable flap. AB - PURPOSE: Major injuries of the hand with skin loss often require early flap cover, which should be versatile, simple in technique, and safe. The reverse posterior interosseus flap satisfies all of these requirements. Over the years, refinements in the technique of harvesting this flap have evolved to prevent venous congestion and flap necrosis. This study presents adaptations to avoid such complications and raise a successful flap. METHODS: A total of 21 patients underwent this flap reconstruction between January 2008 and November 2010 for injuries around the wrist and hand. The average follow-up period was 6 months; 19 were male and 2 were female. The average age was 33 years (range, 9-70 y). In 17 patients, the flap reconstructions were done for posttraumatic injuries, in 2 after skin defects following tumor resection, and 1 each after defects resulting from release of first web contracture in multiple congenital contractures and burns. Average size of the flap was 51 cm(2) (range, 90- 30 cm(2)). The donor area was covered by a split skin graft. RESULTS: All flaps survived without major complications. Generally the flap matched the surrounding skin except for palmar defects. No patients reported donor skin graft color mismatch. CONCLUSIONS: The reverse posterior interosseous flap is a reliable and safe flap for soft tissue cover to the wrist, palm, dorsum of hand, first web space, and metacarpophalangeal joints. Thorough attention to the technical details, including performing a proximo-distal flap dissection with the deep fascia, avoiding dissection of the anastomotic arc between posterior and anterior interosseous artery, creating a broad pedicle with a cutaneous handle, and avoiding its tunneling for inset, will contribute to survival of the flap. PMID- 22321439 TI - Incidence and characteristics of carpal fractures occurring concurrently with distal radius fractures. AB - PURPOSE: To investigate the incidence and characteristics of carpal fractures occurring concurrently with distal radius fractures and to determine the risk factors for this combination. METHODS: We retrospectively analyzed 161 consecutive patients with 170 distal radius fractures who were treated between 2007 and 2011. Posteroanterior, lateral, and oblique radiographs of the wrist were examined, as were computed tomography scans when available. We evaluated the incidence and characteristics of carpal fractures occurring concurrently with distal radius fractures and the patient factors of gender, age, AO/ASIF classification, and energy of the injury. RESULTS: Of the 170 distal radius fractures, 11 (7%) also had 1 or 2 carpal fractures. Of the 15 carpal fractures, 8 were scaphoid, 2 triquetrum, 2 pisiform, 1 capitate, 1 trapezium, and 1 hamate. Eleven of the 15 carpal fractures were diagnosed by computed tomography alone. Male gender, patients of lower mean age, AO/ASIF type B, and high-energy trauma significantly raised the risk of simultaneous fractures of the distal radius and carpals. CONCLUSIONS: The incidence of carpal fractures occurring concurrently with distal radius fractures was not negligible, and almost all carpal fractures had no or minimal displacement. Suspicion of carpal fractures occurring concurrently with distal radius fracture should be high, and computed tomography should be considered, in males, young patients, and those with AO/ASIF type B fractures and high energy trauma. PMID- 22321440 TI - Molecular phylogeny of tintinnid ciliates (Tintinnida, Ciliophora). AB - We investigated the phylogeny of tintinnids (Ciliophora, Tintinnida) with 62 new SSU-rDNA sequences from single cells of 32 marine and freshwater species in 20 genera, including the first SSU-rDNA sequences for Amphorides, Climacocylis, Codonaria, Cyttarocylis, Parundella, Petalotricha, Undella and Xystonella, and 23 ITS sequences of 17 species in 15 genera. SSU-rDNA phylogenies suggested a basal position for Eutintinnus, distant to other Tintinnidae. We propose Eutintinnidae fam. nov. for this divergent genus, keeping the family Tintinnidae for Amphorellopsis, Amphorides and Steenstrupiella. Tintinnopsis species branched in at least two separate groups and, unexpectedly, Climacocylis branched among Tintinnopsis sensu stricto species. Tintinnopsis does not belong to the family Codonellidae, which is restricted to Codonella, Codonaria, and also Dictyocysta (formerly in the family Dictyocystidae). The oceanic genus Undella branched close to an undescribed freshwater species. Metacylis, Rhabdonella and Cyttarocylis formed a well supported clade with several Tintinnopsis species at a basal position. Petalotricha ampulla and Cyttarocylis cassis SSU-rDNA and ITS sequences were identical or almost identical. Therefore, we propose Cyttarocylis ampulla comb. nov. for them. Intensive use of single-cell isolation and sequencing revealed unexpected complexity in the evolutionary history of these relatively well-studied ciliates. Notably, the diversity of freshwater forms suggests multiple marine-freshwater invasions. PMID- 22321441 TI - Metastatic adenosquamous carcinoma of the foot: a case report. AB - Metastasis of carcinoma to the bones of the foot is rare and carries with it a very poor prognosis for patients. Acrometastasis can be the initial manifestation of an occult cancer or widespread metastasis of a previously diagnosed cancer. A high level of suspicion and timely diagnosis are essential to the timely diagnosis and treatment of this condition. In this report, a case of metastatic non-small cell lung carcinoma to the first metatarsal, intially diagnosed as acute gout, is presented. PMID- 22321442 TI - Reciprocal relationship between social support and psychological distress among a national sample of older adults: an autoregressive cross-lagged model. AB - In this study we examined the longitudinal relationships between five dimensions of social support and psychological distress to determine whether (1) social support was related to subsequent psychological distress levels; or (2) if distress levels were related to subsequent social support levels; or (3) if distress and support had a reciprocal (bi-directional) relationship across time. Using bivariate autoregressive cross-lagged models, we analysed data from 2,564 older adults. We found support for the reciprocal relationship between affectionate support and distress. Higher psychological distress was related to subsequently higher levels of positive social interaction, and significantly related to subsequently higher emotional/informational support. No significant relationship was found between tangible and structural support and psychological distress. This study demonstrates that different types of support are associated in correspondingly different ways with psychological distress, and that psychological distress may be important in predicting levels of social support two years later. PMID- 22321444 TI - Assessment of maladaptive variants of Five-Factor Model traits. AB - Research has shown that the personality disorders (PDs) bear consistent relations to general models of personality functioning, particularly in relation to the Five-Factor Model (FFM). In addition to suggesting that the PDs might be understood as constellations of traits from the FFM, this research also suggests that these constellations might be used to assess the PDs. The present article reviews previous research using the NEO Personality Inventory-Revised (NEO PI-R; Costa & McCrae, ) to assess disordered personality and discusses some shortcomings of this approach. Next, I detail studies that have used what is known about the relations between the FFM and disordered personality to construct new assessments that are grounded in the basic science of personality but designed to assess the more pathological aspects. Finally, the advantages of this approach are outlined. PMID- 22321443 TI - MoSwi6, an APSES family transcription factor, interacts with MoMps1 and is required for hyphal and conidial morphogenesis, appressorial function and pathogenicity of Magnaporthe oryzae. AB - The Magnaporthe oryzae mitogen-activated protein kinase (MAPK) MoMps1 plays a critical role in the regulation of various developmental processes, including cell wall integrity, stress responses and pathogenicity. To identify potential effectors of MoMps1, we characterized the function of MoSwi6, a homologue of Saccharomyces cerevisiae Swi6 downstream of MAPK Slt2 signalling. MoSwi6 interacted with MoMps1 both in vivo and in vitro, suggesting a possible functional link analogous to Swi6-Slt2 in S. cerevisiae. Targeted gene disruption of MoSWI6 resulted in multiple developmental defects, including reduced hyphal growth, abnormal formation of conidia and appressoria, and impaired appressorium function. The reduction in appressorial turgor pressure also contributed to an attenuation of pathogenicity. The DeltaMoswi6 mutant also displayed a defect in cell wall integrity, was hypersensitive to oxidative stress, and showed a significant reduction in transcription and activity of extracellular enzymes, including peroxidases and laccases. Collectively, these roles are similar to those of MoMps1, confirming that MoSwi6 functions in the MoMps1 pathway to govern growth, development and full pathogenicity. PMID- 22321445 TI - An interdisciplinary learning experience in neuro-optics. AB - How can a Ph.D. student initially trained as a biologist take part in the development of a multineuronal recording method that requires cross interaction between physics, neurobiology and mathematics? Beyond student training in the laboratory, interdisciplinary research calls for a new style of academic training of young researchers. Here we present an innovative approach to graduate student academic training that fills the need for multidisciplinary knowledge and provides students, in addition, with a deeper understanding of the interdisciplinary approach to scientific research. PMID- 22321446 TI - [Imaging in primary pleuropulmonary synovial sarcoma]. PMID- 22321447 TI - [Coronary CT angiography using a prospective protocol. Comparison of image quality and radiation dose between dual source CT and single source CT]. AB - OBJECTIVE: To compare the image quality and radiation dose in a group of patients undergoing coronary CT angiography using a 128-slice dual source helical CT scanner with high pitch alto and prospective acquisition with those in a group of patients with similar clinical characteristics undergoing coronary CT angiography using a 128-slice single-source CT scanner with prospective sequential acquisition. MATERIAL AND METHODS: We included 80 patients with heart rates <=65 beats/min: 40 underwent sequential 128-slice single source CT with prospective synchronization and the other 40 underwent 128-slice dual source helical CT with high pitch and prospective synchronization. Two radiologists independently assessed the quality of the images of the coronary arteries on the 80 coronary CT angiograms: image quality was classified on a four-point scale in which 1 represented excellent and 4 deficient. The effective dose of radiation was also calculated. RESULTS: The clinical characteristics of the patients in the two groups were similar. The image quality obtained with dual source CT was significantly better than that obtained with single source CT (P=0.006). The mean effective dose of radiation in the group undergoing dual source CT was 36% lower than in the group undergoing single source CT (1.4+/-0.6 mSv vs. 2.2+/-0.9 mSv; P<0.01). CONCLUSION: Although both sequential 128-slice single source CT with prospective acquisition and 128-slice dual source helical CT with high pitch and prospective acquisition provide good image quality and low effective doses of radiation, 128-slice dual source helical CT with prospective acquisition provides better image quality and results in a lower effective dose of radiation. PMID- 22321448 TI - Computational prediction of MicroRNAs targeting GABA receptors and experimental verification of miR-181, miR-216 and miR-203 targets in GABA-A receptor. AB - BACKGROUND: GABA receptors are well known as the inhibitory receptors in the central nervous system and are also found in peripheral tissues. We have previously shown that GABA receptors are involved in lung development and fluid homeostasis. However, the microRNAs that regulate GABA receptors have not yet been identified. RESULTS: In this study, we used the online software, TargetScan and miRanda, to query the microRNAs that directly target GABA receptors and then selected some of them to verify experimentally using 3'-UTR reporter assays. Computational approaches predict many microRNA binding sites on the 3'-UTR of GABAA receptors, but not on GABAC receptors. 3'-UTR reporter assays only verified miR-181, miR-216, and miR-203 as the microRNAs that target GABA receptor alpha1 subunit among 10 microRNAs tested. CONCLUSIONS: Our studies reinforce that microRNA target prediction needs to be verified experimentally. The identification of microRNAs that target GABA receptors provides a basis for further studies of post-transcriptional regulation of GABA receptors. PMID- 22321449 TI - Molecular demonstration of Trypanosoma evansi and Trypanosoma lewisi DNA in wild rodents from Cambodia, Lao PDR and Thailand. AB - In this study, we investigated the molecular evidence of Trypanosoma evansi in wild rodents from Cambodia, Lao PDR and Thailand. Between November 2007 and June 2009, 1664 rodents were trapped at eight sites representative of various ecological habitats. Of those animals, 94 were tested by direct microscopic blood examination, 633 using the Card Agglutination Test for Trypanosomes (CATT/T. evansi) and 145 by Polymerase Chain Reaction (PCR) with two sets of primers: TRYP1 (amplifying ITS1 of ribosomal DNA of all trypanosomes) and TBR (amplifying satellite genomic DNA of Trypanozoon parasites). Using TRYP1, based on the size of the PCR products, 15 samples from the three countries were positive for Trypanosoma lewisi (two were confirmed by sequencing), and three were positive for Trypanozoon (one was confirmed by sequencing and three by TBR primers); the specificity of the primers failed as rodent DNA was amplified in some cases. Using TBR, six samples were positive for Trypanozoon (one was confirmed by sequencing); as T. evansi is the only species of the Trypanozoon sub-genus possibly present in Asian rodents, these results confirmed its presence in rodents from Thailand (Rattus tanezumi) and Cambodia (R. tanezumi, Niviventer fulvescens & Maxomys surifer). Further investigations are necessary to establish the situation in Lao PDR. None of the 16 samples most strongly positive to the CATT proved to be positive for Trypanozoon by PCR. The merits of the CATT for such studies were not confirmed. Studying the urban and rural circulation of these parasites in rodents will enable an evaluation of human exposure and infection risk, as human infections by T. evansi were recently described in India and by T. lewisi in India and Thailand. As sequencing PCR products is expensive, the development of new molecular and serological tools for rodents would be very useful. PMID- 22321450 TI - The cumulative effects of medication use, drug use, and smoking on erectile dysfunction among men who have sex with men. AB - INTRODUCTION: Erectile dysfunction (ED) is highly prevalent among human immunodeficiency virus-seropositive (HIV+) men who have sex with men (MSM). There is a need for additional research to determine the correlates of HIV+ and HIV seronegative (HIV-) MSM, especially regarding nonantiretroviral medication use. AIMS: This study examined the prevalence of ED and the sociodemographic, medical conditions, medication use, and substance use correlates of ED among HIV+ and HIV MSM. METHODS: A modified version of the International Index of Erectile Function (IIEF) for MSM was self-administered by participants enrolled in the Multicenter AIDS Cohort Study, an ongoing prospective study of the natural and treated histories of HIV infection among MSM in the United States. The study sample included 1,340 participants, including 612 HIV+ and 728 HIV- men. Poisson regression with robust error variance was used to estimate prevalence ratios of ED in multivariable models in combined (HIV+/-) and separate analyses. MAIN OUTCOME MEASURE: ED was determined by the summed scores of a modified version of the IIEF validated among MSM. RESULTS: Twenty-one percent of HIV+ MSM and 16% of HIV- MSM reported ED. Being >55 years of age, black race, cumulative pack years of smoking, cumulative antihypertensive use, and cumulative antidepressant use had significant positive associations with the prevalence of ED in the total sample. Among HIV+ men, duration of antihypertensive use and antidepressant use were significantly associated with increasing prevalence of ED. Among HIV- men, being >55 years of age, black race, and cigarette smoking duration were associated with increased prevalence of ED. CONCLUSION: Predictors of ED may differ by HIV status. Although smoking cessation and effective medication management may be important as possible treatment strategies for ED among all MSM, there may be a burden on sexual functioning produced by non-HIV medications for HIV+ men. PMID- 22321451 TI - Minimizing sleep deprivation effects in healthy adults by differential outcomes. AB - Sleep deprivation reduces vigilance or arousal levels, affecting the efficiency of certain cognitive functions such as learning and memory. Here we assessed whether the differential outcomes procedure (DOP), a learning procedure that has proved useful to ameliorate episodic memory deficits, can also improve memory performance in sleep-deprived participants. Photographs were presented as sample faces. A probe face was then presented for recognition after either short or long delays. In the differential outcomes condition a unique reinforcer followed correct responses. In the non-differential outcomes condition reinforcers were provided in a random manner. The results indicated that the DOP prevented the recognition memory to decrement during the long delay in the control group, replicating previous findings. The sleep-deprived group showed DOP benefits mainly with the short delay, when working memory could be affected by low arousal. These findings confirm that the DOP can overcome impaired recognition memory due to sleep deprivation conditions. PMID- 22321452 TI - The origin of children's implanted false memories: memory traces or compliance? AB - A longstanding question in false memory research is whether children's implanted false memories represent actual memory traces or merely result from compliance. The current study examined this question using a response latency based deception task. Forty-five 8-year-old children received narratives about a true (first day at school) and false event (hot air balloon ride). Across two interviews, 58/32% of the participants developed a partial/full false memory. Interestingly, these children also showed higher false recall on an unrelated DRM paradigm compared to children without a false memory. The crucial finding, however, was that the results of the deception task revealed that children with partial and full false memories were faster to confirm than to deny statements relating to the false event. This indicates that children's implanted false memories reflect actual memory traces, and are unlikely to be explained by mere compliance. PMID- 22321453 TI - The end-state comfort effect facilitates joint action. AB - Motor experts can accurately predict the future actions of others by observing their movements. This report describes three experiments that investigate such predictions in everyday object manipulations and test whether these predictions facilitate responses to the actions of others. Observing video excerpts showing an actor reaching for a vertically mounted dial, participants in Experiment 1 needed to predict how the actor would rotate it. Their predictions were specific to the direction and extent of the dial rotation and improved proportionate to the length of the video clip shown. Testing whether such predictions facilitate responses, in the subsequent experiments responders had to undo an actor's actions, back-rotating a dial (Exp 2) and a bar (Exp 3). The responders' actions were initiated faster when the actors' movements obeyed the so-called end-state comfort principle than when they did not. Our experiments show that humans exploit the end-state comfort effect to tweak their predictions of the future actions of others. The results moreover suggest that the precision of these predictions is mediated by perceptual learning rather than by motor simulation. PMID- 22321454 TI - Age-of-acquisition affects word naming in Italian only when stress is irregular. AB - In Italian, effects of age of acquisition (AoA) have been found in object naming, semantic categorization of words and lexical decision, but not in word naming (reading aloud). The lack of an AoA effect in Italian word naming is replicated in Experiment 1 which involved reading aloud two-syllable words which all have regular spelling-sound correspondences and regular stress patterns. Studies of English word naming have reported stronger effects of AoA for irregular or exception words than for words with regular, consistent spelling-sound correspondences. There are no grapheme-phoneme irregularities in Italian, but words containing three or more syllables can carry either regular stress on the penultimate syllable or irregular stress on the antepenultimate syllable. Experiment 2 found effects of AoA on reading three-syllable words for words with irregular stress. The results are interpreted in terms of the 'mapping hypothesis' of AoA, with effects arising as a result of a difficulty to generalize earlier-acquired patterns to irregular late-acquired words. PMID- 22321455 TI - The unique contributions of the facilitation of procedural memory and working memory to individual differences in intelligence. AB - Individual differences in working memory account for a substantial portion of individual differences in complex cognitive processes (e.g., comprehension) and fluid intelligence. However, a large portion of the variance in fluid intelligence and comprehension is unexplained. The current investigation was conducted to evaluate whether individual differences in the facilitation of procedural memory accounts for unique variance in intelligence not accounted for by working memory. To measure variability in the facilitation of procedural memory, we used a task that required participants to first classify exemplars of two categories; facilitation was then operationalized by subsequent improvements in the speed of classifying new exemplars from those categories (i.e., an operation-specific memory procedure). Three measures of each focal construct (facilitation in procedural memory, working memory, comprehension and fluid intelligence) were administered to 256 participants. We used structural equation modeling to examine the relationships among these latent variables. Working memory did account for variance in fluid intelligence and comprehension, but most important, individual differences in facilitation of procedural memory accounted for unique variance in fluid intelligence and comprehension. PMID- 22321456 TI - The perceptual span during foveally-demanding visual target localization. AB - Foveally-induced processing load deteriorates target localization performance in vision-guided tasks. Here, participants searched for a target embedded among coded distractors. High processing load was effected by instructing some participants to use the coded distractors to guide their search for the target. Other participants (in the low processing load condition) were not apprised of the code. The experiment examined whether increased processing load alters the span of effective processing (i.e. perceptual span) by (a) reducing its size, (b) altering its shape, or (c) reducing its size and altering its shape. The results demonstrated a reduction in the size of the perceptual span, with no significant change to its shape. It is argued that when distractors are processed beyond simply rejecting them as non targets, the perceptual span shrinks with increasing processing load. The findings are discussed in contrast to a general interference theory that predicts a change in vision-guided performance without a shrinking of the perceptual span. PMID- 22321457 TI - Spatial reversal learning is robust to total sleep deprivation. AB - Sleep deprivation affects cognitive functions that depend on the prefrontal cortex (PFC) such as cognitive flexibility, and the consolidation of newly learned information. The identification of cognitive processes that are either robustly sensitive or robustly insensitive to the same experimental sleep deprivation procedure, will allow us to better focus on the specific effects of sleep on cognition, and increase understanding of the mechanisms involved. In the present study we investigate whether sleep deprivation differentially affects the two separate cognitive processes of acquisition and consolidation of a spatial reversal task. After training on a spatial discrimination between two levers in a Skinner box, male Wistar rats were exposed to a reversal of the previously learned stimulus-response contingency. We first evaluated the effect of sleep deprivation on the acquisition of reversal learning. Performance on reversal learning after 12h of sleep deprivation (n=12) was compared to performance after control conditions (n=12). The second experiment evaluated the effect of sleep deprivation on the consolidation of reversal learning; the first session of reversal learning was followed by 3h of nap prevention (n=8) or undisturbed control conditions (n=8). The experiments had sufficient statistical power (0.90 and 0.81, respectively) to detect differences with medium effect sizes. Neither the acquisition, nor the consolidation, of reversal learning was affected by acute sleep deprivation. Together with previous findings, these results help to further delineate the role of sleep in cognitive processing. PMID- 22321459 TI - Isolation-induced behavioural changes in a genetic animal model of depression. AB - Depression is a heterogeneous disorder displaying a range of symptoms including feelings of despair and social withdrawal. Social isolation may complicate the progression of depression and have effects on both behaviour and physiology. The aim of this study was to investigate the effects of social isolation on behavioural and metabolic parameters in a genetic rat model of depression, the Flinders Sensitive and Resistant Line (FSL/FRL) rats. Rats were housed either individually (social isolation) or pair-housed for 5weeks, and subjected to behavioural testing and metabolic evaluation. We found that social isolation erased the characteristic difference in depressive-like behaviour, measured as immobility in the forced swim test, between the FSL and FRL rats. Social isolation affected both strains equally in impairing object recognition memory, while leading to an increased explorative behaviour in the elevated plus maze test. Surprisingly, single-housed FRL rats showed an increased food intake compared to pair-housed FRL rats, whereas no difference in food intake or body weight was evident in FSL rats. Our results indicate that social isolation for 5weeks causes behavioural alterations, independent of strain. As the changes in appetite were only observed in the FRL rats, this may suggest that this strain responds to the stress of isolation by a change in feeding behaviour. PMID- 22321458 TI - The role of the estrogen receptor alpha in the medial preoptic area in sexual incentive motivation, proceptivity and receptivity, anxiety, and wheel running in female rats. AB - Ovariectomized females were given an infusion in the medial preoptic area (MPOA) of a viral vector carrying either a shRNA directed against the estrogen receptor alpha (ERalpha) or luciferase. The females were subjected to a test for sexual incentive motivation immediately followed by a test for receptivity and proceptive behaviors. Two weeks later they were tested in the light/dark choice procedure, and after another 2 weeks they were subjected to a test in a brightly lit open field. Finally, the females were given free access to a running wheel for 88h. The females were treated with estradiol benzoate (EB), 18 or 1.5MUg/kg, in randomized order 52h before each test except the running wheel. In that experiment, they were given EB 48h after introduction into the wheel cage. They were given progesterone, 1mg/rat, about 4h before all tests, except the running wheel. The shRNA reduced the number of ERalpha with 83%. Females with few ERalpha in the MPOA showed increased lordosis quotient after the 1.5MUg/kg dose of EB. There was no effect on proceptive behaviors or on rejections. When given the 18MUg/kg EB dose, there was no difference between females with few preoptic ERalpha and controls. In the test for sexual incentive motivation, females with few preoptic ERalpha approached the castrated male incentive more than controls, regardless of EB dose. They also moved a shorter distance. In the light/dark choice test as well as in the open field, females with few ERalpha in the MPOA showed signs of reduced fear/anxiety, since they spent more time in the light part of the dark/light box and in the center of the open field. Finally, the data from the running wheel showed that females with few preoptic ERalpha failed to show enhanced activity after treatment with EB. These data show that the preoptic ERalpha inhibits lordosis in females with an intermediate level of receptivity while it fails to do so in fully receptive females. The ERalpha in the MPOA seems to be necessary for selective approach to a sexual incentive. Finally, activation of this receptor appears to have anxiogenic effects in the procedures employed here. A hypothesis for how all these actions of the preoptic ERalpha contributes to efficient reproductive behavior is outlined. PMID- 22321460 TI - Germline pharmacogenomics in oncology: decoding the patient for targeting therapy. AB - Pharmacogenomics is the study of genetic factors determining drug response or toxicity. The use of pharmacogenomics is especially desirable in oncology because the therapeutic index of oncology drugs is often narrow, the need for favorable drug response is often acute, and the consequences of drug toxicity can be life threatening. In this review, we examine the state of pharmacogenomics in oncology, focusing only on germline pharmacogenomic variants. We consider several critical points when assessing the quality of pharmacogenomic findings and their relevance to clinical use, and discuss potential confounding factors limiting interpretation and implementation. Several of the most extensively studied drug gene pairs (irinotecan and UGT1A1; tamoxifen and CYP2D6; 5-fluorouracil and DPYD) are inspected in depth as illustrations of both the state of advancement-and the current limitations of-present knowledge. We argue that there will likely soon be a critical mass of important germline pharmacogenomic biomarkers in oncology which deserve clinical implementation to provide optimal, personalized oncologic care. We conclude with a vision of how routine clinical testing of such germline markers could one day change the paradigm for cancer care. PMID- 22321461 TI - New perspectives in hepatic encephalopathy. AB - The terminology of hepatic encephalopathy (HE) remained poorly defined for decades. One major problem was the lack of definition of what constituted acute versus chronic HE. Chronic HE caused more confusion because it was proposed to signify any bout of HE in patients with chronic liver disease, whereas others thought it denoted a protracted period of loss of consciousness. Numerous other versions were rampant. This mass confusion was solved by the report of the Hepatic Encephalopathy Consensus Group at the World Congress of Gastroenterology in 1998. This new multi-axial definition led to standardization of diagnosis and explosion in the field of research in HE. PMID- 22321462 TI - Theories of the pathogenesis of hepatic encephalopathy. AB - The earliest hypothesis of the pathogenesis of HE implicated ammonia, although effects of appreciable concentrations of this neurotoxin did not resemble HE. Altered eurotransmission in the brain was suggested by similarities between increased GABA-mediated inhibitory neurotransmission and HE, specifically decreased consciousness and impaired motor function. Evidence of increased GABAergic tone in models of HE has accumulated; potential mechanisms include increased synaptic availability of GABA and accumulation of natural benzodiazepine receptor ligands with agonist properties. Pathophysiological concentrations of ammonia associated with HE, have the potential of enhancing GABAergic tone by mechanisms that involve its interactions with the GABAa receptor complex. PMID- 22321463 TI - Assessment and usefulness of clinical scales for semiquantification of overt hepatic encephalopathy. AB - Hepatic encephalopathy (HE) represents the effects of liver dysfunction on the brain. When HE is clinically obvious (eg, confusion, poor judgment, personality change), it is termed overt HE. The severity of HE is measured by different methods. Assessing the severity of HE is important for determining patient prognosis and effectiveness of therapy. This article discusses the different methods for grading HE, including clinical rating scales, neuropsychological tests, and neurophysiologic measures. PMID- 22321464 TI - Assessment of minimal hepatic encephalopathy (with emphasis on computerized psychometric tests). AB - Minimal hepatic encephalopathy (MHE) is associated with a high risk of development of overt hepatic encephalopathy, impaired quality of life, and driving accidents. The detection of MHE requires specialized testing because it cannot, by definition, be diagnosed on standard clinical examination. Psychometric and neurophysiologic techniques are often used to test for MHE. Paper-pencil psychometric batteries and computerized tests have proved useful in diagnosing MHE and predicting its outcomes. Neurophysiologic tests also provide useful information. The diagnosis of MHE is an important issue for clinicians and patients alike. Testing strategies depend on the normative data available, patient comfort, and local expertise. PMID- 22321465 TI - Brain imaging and hepatic encephalopathy. AB - Novel imaging techniques allow the investigation of structural and functional neuropathology of hepatic encephalopathy in greater detail, but limited techniques are applicable to the clinic. Computed tomography and magnetic resonance imaging (MRI) can rule out other diagnoses and, in MRI, give diagnostic features in widely available sequences. An internationally accepted diagnostic framework that includes an objective imaging test to replace or augment psychometry remains elusive. Quantitative MRI is likely to be the best candidate to become this test. The utility of MR and nuclear medical techniques to the clinic and results from recent research are described in this article. PMID- 22321466 TI - Management of overt hepatic encephalopathy. AB - Hepatic encephalopathy (HE) is a potentially reversible state of impaired cognitive function or altered consciousness in patients with liver disease or portosystemic shunting. Overt HE is a particularly pressing problem. Given the many targets of treatment and lack of a clear singular cause of overt HE, there is no consensus on a single best treatment. Over the past several years, high quality studies have been conducted on the various pharmacologic therapies for HE and, as more data emerge, hopefully HE will become a much more easily treated complication of decompensated liver disease. PMID- 22321467 TI - Management of covert hepatic encephalopathy. AB - Employability, driving capacity, and many domains of health-related quality of life are reduced in patients with minimal hepatic encephalopathy (HE). Moreover, once minimal HE is identified, more than 50% of patients develop overt HE within 30 months. Now that minimal HE has been shown to be associated with consequences, more studies are needed to assess the cost effectiveness to treat it. This article discusses the issues regarding diagnosis and management of minimal HE, now called "Covert HE." PMID- 22321469 TI - Hepatic encephalopathy after transjugular intrahepatic portosystemic shunt. AB - Transjugular intrahepatic portosystemic shunt (TIPS) has been used for more than 20 years to treat some of the complications of portal hypertension. When TIPS was initially proposed, it was claimed that the optimal calibration of the shunt could allow an adequate reduction of portal hypertension, avoiding, at the same time, the occurrence of hepatic encephalopathy (HE), a neurologic syndrome. However, several clinical observations have shown that HE occurred rather frequently after TIPS, and HE has become an important issue to be taken into consideration in TIPS candidates and a problem to be faced after the procedure. PMID- 22321470 TI - Extent of reversibility of hepatic encephalopathy following liver transplantation. AB - Although hepatic encephalopathy (HE) is prevalent in the cirrhotic population, it has also been considered a potentially reversible condition. Liver transplantation represents the ultimate reversal of the decompensated cirrhotic state and should provide the best option for the reversibility of HE. However, the neurologic compromise associated with HE in the cirrhotic patient may not be completely reversible. Theories regarding fixed structural and reversible metabolic deficits as well as persistence of the hyperdynamic state with continued portosystemic shunting have been proposed to explain this lack of complete reversibility. Whether this remnant neurologic deficit is clinically significant remains unclear. PMID- 22321471 TI - Hepatic encephalopathy and health-related quality of life. AB - The impact of overt hepatic encephalopathy on health-related quality of life is well defined, but it remains to be demonstrated how much the presence of minimal hepatic encephalopathy (MHE) might impair patients' perceived health status. MHE reduces cognitive abilities, with specific impairment in manual abilities, which can lead to a depressed mood that impairs perceived health status. Therefore, all subjects with cirrhosis should be systematically screened for MHE by validated tools. Early detection and treatment is mandatory to improve the quality of life of patients with advanced cirrhosis, their social isolation, and their daily lives. PMID- 22321468 TI - Malnutrition in cirrhosis: contribution and consequences of sarcopenia on metabolic and clinical responses. AB - Malnutrition is the most common, reversible complication of cirrhosis that adversely affects survival, response to other complications, and quality of life. Sarcopenia, or loss of skeletal muscle mass, and loss of adipose tissue and altered substrate use as a source of energy are the 2 major components of malnutrition in cirrhosis. Current therapies include high protein supplementation especially as a late evening snack. Exercise protocols have the potential of aggravating hyperammonemia and portal hypertension. Recent advances in understanding the molecular regulation of muscle mass has helped identify potential novel therapeutic targets including myostatin antagonists, and mTOR resistance. PMID- 22321472 TI - Hepatic encephalopathy: an update. Preface. PMID- 22321473 TI - Nonoperative management of contained retrohepatic caval injury. AB - Traumatic inferior vena cava (IVC) injuries are associated with high mortality rates, despite all improvements in the technical skills and prehospital and hospital care. Selective conservative management of the penetrating abdominal injuries involving IVC has not been widely discussed before. Here, we report a case of a young female with a single gunshot wound to her abdomen, who presented to our level 1 trauma center 10 minutes after injury and was hemodynamically stable. A computed tomographic scan revealed a large liver laceration with a trajectory through the liver and the IVC. The IVC was surrounded by a moderate amount of fluid, consistent with a contained retroperitoneal hematoma. We discuss the outcome of nonoperative management of this patient along with a review of the literature. PMID- 22321474 TI - Popliteal artery entrapment syndrome in a young girl: case report of a rare finding. AB - The popliteal artery (PA) entrapment syndrome, a rare cause of arterial thrombosis, is most often encountered in young male athletes. Here, we report a very unusual case of PA entrapment syndrome in a 14-year-old girl who presented with a 1-month history of calf claudication to our observation facility. Diagnostic work-up revealed obesity, sedentary lifestyle, and an aberrant accessory slip of the medial head of gastrocnemius around the PA. Arterial echo color Doppler ultrasonography and computed tomographic angiography studies were performed. Surgical treatment involved revascularization with resection of the medial head of gastrocnemius, the cause of the arterial entrapment, and enlargement angioplasty using an autologous saphenous vein patch, in combination with antiplatelet therapy, resulting in restitution ad integrum of the affected limb and, finally, an improved quality of life of the patient. This case underscores the importance of clinical suspicion, diagnosis, and treatment of lower-limb claudication in very young patients presenting with unusual symptoms. If missed, the condition may evolve dramatically. Prompt diagnosis and surgical treatment are key to complete recovery and the prevention of irreversible complications that may result in limb loss. PMID- 22321475 TI - Distalization of the anastomosis: an effective treatment for dialysis access associated steal syndrome. AB - Steal syndrome after arteriovenous fistula formation for dialysis access can cause ischemic pain and tissue loss. This is an indication for surgical revision, usually either banding (or ligation) or the distal revascularisation and interval ligation procedure. However, banding is inexact, and distal revascularisation and interval ligation can further compromise the arterial supply to the arm. We report three cases in which an alternative approach of moving the arteriovenous anastomosis distally was used, thereby protecting arterial inflow to the hand. In all three cases, the steal resolved and the fistula remained patent. PMID- 22321476 TI - Incidental findings in patients evaluated for thoracic aortic pathology using computed tomography angiography. AB - BACKGROUND: Computed tomography angiography (CTA) is routinely used to diagnose thoracic aortic pathology and for surveillance after thoracic endovascular aortic repair. The purpose of our study was to assess the prevalence of unsuspected disease identified on CTA examination for thoracic aortic pathology and to determine potential clinical significance of these findings. METHODS: A retrospective review of 242 patients (136 men and 106 women; mean age, 65.7 +/- 13.9 years) referred for clinical evaluation of thoracic aortic pathology during a 12-year period was performed. CTA was acquired after obtaining full written informed consent and injecting nonionic contrast Omnipaque 350 intravenously. Subsequently, axial images were obtained from the thoracic inlet through the pubic symphysis. The prevalence of incidental findings was recorded. A finding was judged potentially significant if a therapeutic intervention or radiologic follow-up was deemed advisable on the basis of the CTA findings. RESULTS: Prevalence of incidental findings were noncalcified pulmonary lesions (subcentimeter nodule [28, 11.57%], nodule >1 cm [16, 6.61%], and pulmonary mass >3 cm [4, 1.65%]), calcified pulmonary nodules (35, 14.46%), simple liver cysts (32, 13.22%), contrast-enhancing liver lesion (7, 2.89%), renal mass (7, 2.89%), and pancreatic mass (5, 2.06%). Subsequent diagnostic tests were recommended for 63 findings in 55 (22.72%) patients, which revealed 11 (4.5%) patients had metastatic disease-six primary lung cancer, one metastatic lesion (mets) to the lung, one renal cell carcinoma with mets in the lung, one primary pancreatic adenocarcinoma with mets in the liver, one unknown primary with mets in the liver, and one other poorly differential metastatic carcinoma with lesions in the pancreas, adrenal glands, kidneys, and small bowel with unknown primary. CONCLUSION: CTA evaluation in patient with aortic pathology may reveal a high rate of malignant lesions. Attention to the incidental finding of suspicious lesion on computed tomographic scans in the chest and abdomen and appropriate follow-up by the requesting surgeon is important in patients undergoing surveillance for aortic pathologies. PMID- 22321477 TI - Modified "stent-graft sandwich" technique for treatment of isolated common iliac artery aneurysm in patient with Marfan syndrome. AB - Isolated iliac artery aneurysms are rare in the general population (0.03%) and represent 2% of all abdominal aneurysms, and the association with Marfan syndrome is even rarer. We report a Marfan syndrome case with an isolated common iliac artery aneurysm treated by using a modified "stent-graft sandwich" technique, with preservation of the internal iliac artery perfusion. The modified "stent graft sandwich" technique involves building an appropriate proximal neck just in the common iliac artery for fittingly housing two new stent-grafts inside, both deployed simultaneously and each one going to both distal iliac arteries (internal and external). PMID- 22321478 TI - A case of extrinsic chronic cerebrospinal venous insufficiency in a patient with multiple sclerosis. AB - We aim to present a very rare case of chronic cerebrospinal venous insufficiency due to both brachiocephalic vein obstruction by aberrant right subclavian artery and internal jugular vein distal compression by first cervical vertebra transverse process, demonstrated by multislice computerized tomography in a patient with multiple sclerosis. PMID- 22321479 TI - Percutaneous mechanical thrombectomy for extensive acute lower-extremity deep venous thrombosis in a patient after double-lung transplantation. AB - Venous thromboembolism, which includes deep venous thrombosis (DVT) and pulmonary embolism (PE), has been estimated to affect 25% of patients after major surgery; however, the literature on venous thromboembolism after thoracic transplantation and optimal approach remains limited. We report the status of a 67-year-old female who developed massive right lower-extremity DVT after double-lung transplantation. Because her surgery had taken place a week before this event, it was decided that pharmaco-thrombolysis was contraindicated due to the high risk of bleeding complications in a fresh double-lung transplant recipient. The patient was taken emergently to the operating room for percutaneous mechanical thrombectomy, which provided grade III (complete lysis) and restored venous patency in the affected extremity. This report highlights the successful use of purely percutaneous mechanical thrombectomy for acute DVT in a double-lung recipient, and also advocates inferior vena cava filter placement to prevent embolic events during the mechanical thrombectomy. PMID- 22321480 TI - Benefit of a single dose of preoperative antibiotic on surgical site infection in varicose vein surgery. AB - BACKGROUND: Ligation and division of the saphenofemoral junction (L/D SFJ) can protect against the danger of venous thromboembolism (VTE) associated with greater saphenous vein (GSV) radiofrequency ablation (RFA). Although this procedure is regarded as clean from an infection standpoint, surgical site infection (SSI) can offset its thromboembolic benefit. We questioned whether SSI associated with L/D SFJ could be minimized by a single preoperative dose of antibiotic. METHODS: A retrospective cohort study was performed on 902 ambulatory surgery patients who underwent 953 consecutive RFAs of the GSV in combination with L/D SFJ. A single dose of preoperative antibiotic was administered 1 hour before incision to some patients (n = 449 extremities), with all other patients receiving no antibiotic (n = 504). Primary outcome measure was SSI categorized based on type of therapy required (1: oral antibiotic, 2: hospitalization for intravenous antibiotic and/or wound debridement), with a secondary outcome measure of VTE. RESULTS: VTE occurred in 10 patients (1%) and included three pulmonary emboli. The majority of VTE were calf deep vein thromboses (n = 7). SSI developed in 78 patients (8.2%) with groin, thigh, and calf distributions of 47%, 8%, and 45%, respectively. All category 2 infections (n = 8, 10%) occurred in control subjects, and the majority were located in the groin. Body mass index significantly increased risk for both overall (odds ratio [OR]: 1.09, 95% confidence interval [CI]: 1.05-1.14, P < 0.0001) and groin (OR: 1.08, 95% CI: 1.02-1.14, P = 0.01) SSI as well as VTE (OR: 1.17, 95% CI: 1.08-1.30, P = 0.003). Diabetes was a significant risk for groin SSI (OR: 5.13, 95% CI: 1.44-18.26, P = 0.01). Antibiotic was associated with a significantly reduced risk for both overall (OR: 0.54, 95% CI: 0.37-0.89, P = 0.02) and groin (OR: 0.34, 95% CI: 0.16 0.73, P = 0.01) SSI. Furthermore, prophylaxis eliminated category 2 infections (P = 0.008) and was associated with a significantly lower risk of VTE (OR: 0.11, 95% CI: 0.01-0.85, P = 0.01). Although SSI was noted more commonly in extremities with thromboembolic complications (20% [n = 2] vs. 8.1% [n = 76] in those without), this trend was not significant and could not account for the antibiotic effect on VTE. CONCLUSIONS: L/D SFJ combined with RFA of the GSV, when treated as a clean procedure and not prophylaxed with antibiotic, carries a significant risk of SSI. While diabetes and high body mass index are patient-associated SSI risk factors, a single dose of preoperative antibiotic significantly reduces the rate of all infection, eliminates the danger of serious infection, and is associated with minimal VTE. PMID- 22321481 TI - A comparison between the treatments of functional and nonfunctional carotid body tumors. AB - BACKGROUND: It is well known that carotid body tumors (CBTs) are rare and almost nonfunctional, and that functional CBTs are even less frequently seen, with or without catecholamine-induced symptoms. Objective of this study is to make comparison between the treatment effects on functional and nonfunctional CBTs. METHODS: The medical records of 46 patients (16 men and 30 women) of our unit who underwent surgical intervention for CBTs were retrospectively reviewed from January 2005 to July 2010. Patients were divided into two groups by function: group A (n = 5, functional CBTs) and group B (n = 41, nonfunctional CBTs). Perioperative and postoperative details were compared accordingly. RESULTS: All the patients successfully underwent tumor resection. Although symptoms were nonspecific, intraoperative hypertension (5/5, 100%) and persistent postoperative hypotension (3/5, 60%) were found in group A. No statistical difference was found in perioperative details and complications between two groups. No recurrence occurred in two groups during the follow-up period for a mean of 35.3 months (with a range of 12-60 months). CONCLUSION: Surgical resection is safe and effective even if the CBT is functional. Besides routine preparation, preoperative measurement of serum catecholamine, treatment with alpha- and beta adrenergic blockade and gentle manipulation during operation are necessary. PMID- 22321482 TI - A five-year review of management of upper-extremity arterial injuries at an urban level I trauma center. AB - BACKGROUND: Upper-extremity arterial injuries are relatively uncommon, but they may significantly impact patient outcome. Management of these injuries was reviewed to determine incidence, assess the current management strategy, and evaluate hospital outcome. METHODS: Upper-extremity trauma patients presenting with arterial injury between January 2005 and July 2010 were included in this retrospective review. Descriptive statistics were used to describe demographic, injury, treatment, and outcome data. These variables also were compared between blunt and penetrating arterial injuries and between proximal and distal arterial injuries. RESULTS: During a 5.6-year period, 135 patients with 159 upper extremity arterial injuries were admitted, yielding an incidence of 0.74% among trauma admissions. The majority of patients (78.5%) suffered concomitant upper extremity injuries. The most common injury mechanism was laceration by glass (26.4%). Arterial injuries were categorized into 116 penetrating (73.0%) and 43 blunt (27.0%) mechanisms. Arterial distribution involved was as follows: 13 axillary (8.2%), 40 brachial (25.2%), 52 radial (32.7%), 51 ulnar (32.1%), and 3 other (1.9%). The types of arterial injuries were as follows: 69 transection (43.4%), 68 laceration (42.8%), 16 occlusion (10.1%), 3 avulsion (1.9%), and 3 entrapment (1.9%). One patient (0.7%) required a primary above-elbow amputation. The majority of injuries (96.8%) receiving vascular management underwent surgical intervention--76 primary repair (49.7%), 41 ligation (26.8%), 31 bypass (20.3%), and 5 endovascular (3.3%). Conservative treatment was the primary strategy for five arterial injuries (3.3%). Of the patients receiving vascular intervention, three (2.2%) required major and three (2.2%) required minor amputations during hospitalization and no patients expired. CONCLUSION: The current multidisciplinary team management approach with prompt surgical management resulted in successful outcomes after upper-extremity arterial injuries. No outcome differences between penetrating and blunt or between proximal and distal arterial injuries were calculated. This management approach will continue to be used. PMID- 22321483 TI - Comparison of early and midterm results of open and endovascular treatment of popliteal artery aneurysms. AB - BACKGROUND: Aim of this study was to retrospectively compare perioperative (<30 days) and 2-year results of open and endovascular management of popliteal artery aneurysms (PAAs) in a single-center experience. METHODS: From January 2005 to December 2010, 64 PAAs in 59 consecutive patients were operated on at our institution; in 43 cases, open repair was performed (group 1), whereas the remaining 21 cases had an endovascular procedure (group 2). Data from all the interventions were prospectively collected in a dedicated database, which included main preoperative, intraoperative, and postoperative parameters. Early results in terms of mortality, graft thrombosis, and amputation rates were analyzed and compared by chi(2) text or Fisher exact text. The surveillance program consisted of clinical and ultrasonographic examinations at 1, 6, and 12 months and yearly thereafter. Follow-up results (survival, primary and secondary patency, limb salvage) were analyzed by Kaplan-Meier curves, and differences in the two groups were assessed by log-rank test. RESULTS: There were no differences between the two groups in terms of sex, age, risk factors for atherosclerosis, and comorbidities; PAAs were symptomatic in 48% of cases in group 1 and in 29% in group 2 (P = 0.1). Fifteen patients with mild-to-moderate acute ischemia due to PAA thrombosis underwent preoperative intra-arterial thrombolysis, 13 in group 1 and 2 in group 2. In open surgery group, nine cases were treated with aneurysmectomy and prosthetic graft interposition, and in seven cases, the aneurysm was opened and a prosthetic graft was placed inside the aneurysm. In 27 cases, ligation of the aneurysm with bypass grafting (21 prosthetic grafts and 6 autologous veins) was carried out. In group 2, 20 patients had endoprosthesis placement, whereas in the remaining patient, a multilayer nitinol stent was used. There was one perioperative death in a patient of group 2 who underwent concomitant endovascular aneurysm repair and PAA endografting. Cumulative 30-day death and amputation rate was 4.5% in group 1 and 4.7% in group 2 (P = 0.9). Follow-up was available in 61 interventions (96%) with a mean follow-up period of 22.5 months (range: 1-60). Estimated primary patency rates at 24 months were 78.1% in group 1 and 59.4% in group 2 (P = 0.1). Freedom from reintervention rates at 24 months were 79% in group 1 and 61.5% in group 2 (P = 0.2); estimated 24-month secondary patency rates were 81.6% in group 1 and 78.4% in group 2 (P = 0.9), and freedom from amputation rates were 92.7% and 95%, respectively (P = 0.7). CONCLUSIONS: Endovascular treatment of PAAs provided, in our initial experience, satisfactory perioperative and 1-year results, not significantly different from those obtained with prosthetic open repair in patients with similar clinical and anatomical status. There is, however, a trend toward poorer primary patency rates among patients endovascularly treated, who also seem to require more frequently a reintervention. PMID- 22321484 TI - Challenging treatment of multiple late complications after endovascular aneurysm repair. AB - BACKGROUND: To report a case of multiple additional procedures after successful endovascular treatment of abdominal aortic aneurysm. METHODS: An endovascular abdominal aortic aneurysm repair with a bifurcated aortic Vanguard endograft successfully performed in 1999 resulted in multiple complications, including endoleaks and a row separation, treated endovascularly. Subsequently, tuberculosis sepsis and prosthesis infection resulted in long-term antibiotic treatment. Additional graft leaks, aneurysm sack growth, and sack ruptures were also treated endovascularly because the patient consistently denied open repair. Endovascular procedures, however, did not solve the problem, turning to be increasingly challenging. The patient finally approved open graft removal and aortobifemoral reconstruction that were successfully performed 11 years after the initial endograft implantation. RESULTS: The patient has recovered from surgery well and is asymptomatic. No evidence of bacterial colonization was found according to the specimen taken during the laparotomy. CONCLUSION: Vanguard and other first-generation aortic endografts are associated with high incidence of complications and reinterventions. Open surgery is a method of choice in similar cases. PMID- 22321485 TI - Aortic graft preservation by debridement and omental wrapping. AB - BACKGROUND: Aortic graft infection is a rare, but grave, complication in vascular surgery. Graft removal together with extra-anatomical bypass or in situ graft replacement is usually advocated, but these procedures are associated with significant morbidity and mortality. METHODS AND RESULTS: Two cases of aortic graft infection in high-risk surgical candidates managed by open debridement and omental wrapping with graft preservation are described. Both remain well at 3 years without any adjunctive procedures. CONCLUSION: Debridement and omental wrapping may offer an alternative to graft removal and revascularization in selected patients. This relatively low-risk procedure may allow long-term survival. PMID- 22321486 TI - Aberrant right subclavian artery or arteria lusoria: a rare cause of dyspnea in children. AB - Aberrant right subclavian artery or arteria lusoria (AL) is the most frequent anomaly of the aortic arch, secondary to abnormal embryogenesis. It is usually asymptomatic and fortuitously discovered. It can compress neighboring structures and cause dysphagia or, more rarely, dyspnea. In symptomatic cases or in the presence of an aneurysm of the AL origin, it should be surgically treated. The case herein reported concerns a child presenting with respiratory symptomatology related to an AL that was surgically treated by right supraclavicular approach. PMID- 22321487 TI - Ten-year comparative analysis of bovine pericardium and autogenous vein for patch angioplasty in patients undergoing carotid endarterectomy. AB - BACKGROUND: To evaluate early and late clinical outcomes of carotid endarterectomy (CEA) with bovine pericardium patch in comparison with autogenous vein. METHODS: During a 10-year period, 456 CEAs were performed using patch closure of the arteriotomy with bovine pericardium (252 cases) and autogenous vein (204 cases). Retrospectively, surgical outcomes were evaluated and compared regarding CEA-related parameters, early and late mortality and morbidity rates, and the incidence of restenosis and aneurysmal dilatation between patients with bovine pericardium patch closure and those with autogenous vein closure. RESULTS: The two groups were comparable regarding basic demographics, clinical data, and anatomic data, except the incidence of coronary or peripheral arterial diseases. In patients with bovine pericardium patch closure, the total operating time and carotid clamping duration were statistically significantly shorter than in those with autogenous vein closure (P < 0.01). During the early postoperative period, 10 major (stroke and death) complications (2.2%) occurred without statistically significant difference between the two groups. The incidence of early minor postoperative complications was less with bovine pericardium patch closure (5.6% vs. 10.8%; P < 0.05). With a mean follow-up of 62 months for bovine pericardium patch closure and 67 months for autogenous vein closure, the incidence of restenosis was similar, but aneurysmal dilatation was higher in patients with autogenous vein closure with a statistically significant difference (0% vs. 2.0%; P < 0.05). CONCLUSION: CEA with bovine pericardium patch angioplasty showed excellent early and late clinical outcomes. Our results demonstrated bovine pericardium to be a suitable patch material for routine use in CEA. PMID- 22321488 TI - Combined emergency abdominal aortic aneurysm repair and valve replacement in a patient with severe aortic stenosis. AB - Simultaneous open surgery has been advocated in the elective management of abdominal aortic aneurysm patients with significant ischemic heart disease, as staged procedures risk worsening myocardial ischemia or aortic rupture, depending on which is the first intervention. The argument for combined aneurysm and valve repair is less established. We describe the case of a 70-year-old female who while awaiting aortic valve replacement suffered rupture of an abdominal aortic aneurysm. The patient was successfully managed with emergency combined open abdominal aortic aneurysm repair and open aortic valve replacement. We would advocate that such a strategy be considered as a salvage technique in similarly difficult management dilemmas. PMID- 22321489 TI - Middle colic artery aneurysm: a case report and review of the literature. AB - We report a case of a ruptured middle colic artery (MCA) aneurysm in a 48-year old previously healthy man. Coil embolization was attempted without success. The patient then underwent resection of the MCA and the transverse colon with a satisfactory outcome. Twenty-six previously published cases dating back to 1930 were reviewed, revealing the cause of the MCA aneurysm to be idiopathic in most cases. However, necrotizing arteritis, polyarteritis nodosa, and hypertension have been associated. The aneurysm is commonly managed with laparotomy, as well as arterial resection with or without transverse colectomy, although transcatheter arterial embolization has been successful in four published cases. PMID- 22321490 TI - Rupture of chronic type B aortic dissection in a Jehovah's Witness: successful surgical repair without blood transfusion. AB - The patient, a 55-year-old female Jehovah's Witness who had suffered type B aortic dissection since the age of 53 years, presented with enlargement of the false lumen in the distal aortic arch and was subsequently admitted to our hospital. While hospitalized, her enlarged false lumen ruptured and she underwent replacement of the distal aortic arch and descending thoracic aorta without blood transfusion. Blood conservation strategies for this patient included the following: 1) meticulous hemostasis when incising muscle or soft tissue, 2) minimal use of gauze and discard suckers, 3) exclusive use of a cell salvage device "from skin to skin," 4) low-prime cardiopulmonary bypass, 5) minimal laboratory blood sampling, and 6) preoperative and postoperative erythropoietin treatment. Hemoglobin (Hb) values were 12.5, 15.5, 10.0, and 9.7 g/dL on admission, before rupture, after rupture, and just after the operation, respectively. The patient had an uneventful postoperative course, except for prolonged rehabilitation. The postoperative lowest Hb value was 5.2 g/dL on postoperative day 5, and the Hb value at hospital discharge (postoperative day 55) was 11.0 g/dL. Our experience with blood conservation surgery on this Jehovah's Witness patient suggests that ruptured chronic type B aortic dissection can be safely repaired on bypass through a left thoracotomy with no blood transfusion if the preoperative Hb value is >10.0 g/dL. PMID- 22321491 TI - A digital approach to neutron-gamma imaging with a narrow tungsten collimator aperture and a fast organic liquid scintillator detector. AB - A digital neutron-gamma imaging technique for mixed radiation field is described. The imaging system is based upon an organic liquid scintillator detector, a narrow tungsten collimator, fast digitiser and adjustable equatorial mount. Radioactive sources have been attached to a vertical plane and the digitiser has been used to digitise neutron and gamma events. The digitised events have been discriminated using pulse gradient analysis and images have been generated of the count distribution in the source plane. PMID- 22321492 TI - [Esteem attitude as essential as techniques in the management of glaucoma]. AB - With the tremendous development of medical technology and translational medicine, the level of diagnosis and management for glaucoma has been advanced dramatically in the past decades. Presently, the viewpoint for glaucoma management from specialists in western developed countries has significantly changed, which includes emphasizing resource sharing, formation and generalization of clinical guidelines, and the individualization and humanization in consensus management of glaucoma patients. Such unprecedented importance has been also attached to all round qualities of glaucoma practitioners. The underlying reason for all these marked changes are that esteem attitude is as essential as techniques in the management of glaucoma. PMID- 22321493 TI - [Management of primary open angle glaucoma by paying attention to monitor intraocular pressure fluctuations]. AB - Higher intraocular pressure (IOP) is a risk factor for the development and progression of glaucomatous neuropathy. Increasing attention has been brought to IOP fluctuation in patients with primary open angle glaucoma (POAG) in recent years. IOP fluctuations include short-term (24-hour IOP fluctuations) and long term fluctuations, which may contribute to the progression of glaucoma. It is a big challenge for ophthalmologists in their busy daily clinical practice to deal with IOP fluctuation in patients with POAG. In this paper, the research progress in IOP fluctuation of POAG and its relationship with glaucomatous neuropathy was reviewed. Furthermore, how to monitor by useful measures and manage IOP fluctuation by effective medication were discussed. PMID- 22321494 TI - [Comparison of anterior segment changes before and after laser peripheral iridectomy by anterior segment optical coherence tomography in eyes with primary acute angle closure glaucoma]. AB - OBJECTIVE: To evaluate the changes of anterior segment configuration after surgical peripheral iridectomy (SPI) in patients with primary acute angle closure glaucoma (PAACG) by using anterior segment optical coherence tomography (AS-OCT). METHODS: This retrospective self control study consisted of thirty-seven eyes of 37 patients with PAACG who were consecutively recruited in Zhongshan Ophthalmic Center. The peripheral anterior synechiae (PAS) of these patients was less than 5 clock time point. Central anterior chamber depth (ACD), angle opening distance (AOD), trabecular iris area (TISA), angle recess area (ARA), anterior chamber width (ACW), anterior chamber volume (ACV), and crystalline lens rise (CLR) were measured using AS-OCT before and one month after SPI. RESULTS: After SPI, AOD (0.125 +/- 0.072) um, TISA (0.091 +/- 0.041) mm(2), ARA (0.095 +/- 0.042) mm(2), ACA (14.230 +/- 2.000) mm(2) and ACV (90.074 +/- 16.796) mm(3) were significantly increased compared with before SPI AOD (0.088 +/- 0.078) um, TISA (0.050 +/- 0.048) mm(2), ARA (0.059 +/- 0.057) mm(2), ACA (12.332 +/- 2.457) mm(2), ACV (73.131 +/- 16.976) mm(3) (t = -8.015 to 1.066, P = 0.001 to 0.044), respectively. There were no significantly changes in ACD, ACW and CLR (t = -1.505 to 0.516, P = 0.102 to 0.609). CONCLUSIONS: PAACG can be controlled by SPI resulting in an increase of AOD, TISA, ARA, ACA and ACV, but not ACD or CLR. PMID- 22321495 TI - [The blood-aqueous barrier changes after laser peripheral iridotomy or surgery peripheral iridectomy]. AB - OBJECTIVE: To investigate the ocular blood-aqueous barrier (BAB) alteration after laser peripheral iridotomy (LPI) or surgery peripheral iridectomy (SPI) in patients with primary chronic angle-closure glaucoma (PCACG). METHODS: This was a clinical randomized controlled trial. Sixty eyes of 60 subjects with early stage of PCACG were randomly received either LPI or SPI and followed up postoperatively at day 3, week 1, 2, 3, and 4. Aqueous flare in anterior chamber was measured by FC-2000 flare-cell photometry, intraocular pressure (IOP) measured by tonometer, central corneal endothelium cell counted by endothelioscopy, peripheral anterior synechiae (PAS) detected by gonioscopy. Data were analyzed by using two-way ANOVA for repeated measures, independent samples t-test, paired t-test, nonparametric test, and Spearman rank correlation test. RESULTS: On follow-ups of pre-operative and post-operative 3 days, 1 week (w), 2w, 3w and 4w respectively, the mean aqueous flare values for LPI group were (5.47 +/- 1.09), (11.96 +/- 3.07), (8.08 +/- 2.18), (5.68 +/- 0.83), (5.80 +/- 1.00), (5.69 +/- 1.12) PC/ms, and for SPI group were (5.43 +/- 1.13), (8.44 +/- 3.22), (6.42 +/- 1.77), (5.35 +/- 0.71), (5.53 +/- 1.26), (5.45 +/- 1.23) PC/ms. During post-operative 1w the flare values in both LPI and SPI groups were significantly higher than that on pre-operation (t = -12.753, -8.101, P < 0.05; t = -5.971, -3.870;P < 0.05) and LPI group had a significantly higher mean flare value than SPI group (t = 4.329, 3.231;P < 0.05). The IOP spike in LPI group was significantly (chi(2) = 5.079, 4.022, P < 0.05) higher than that in SPI group at week 1 of post-operation. Increased IOP was positively correlated with BAB damage (r = 0.899, 0.833; P < 0.05). The numbers of medications required to maintain IOP <= 21 mm Hg (1 mm Hg = 0.133 kPa) at week 4 of post-operation in LPI was significantly (Z = -1.984, P < 0.05) more than that in SPI group. There were no significant differences in central corneal endothelium cell count at week 1 (t = -0.696, 0.008) and in extension of PAS at week 4 (Z = -1.270, -1.490) of post-operation when compared to pre-operation (P > 0.05). No obvious complications occurred in both groups. CONCLUSIONS: Our results demonstrated that IOP spike in both of LPI and SPI is due, at least in part, to BAB damage, which appears to be more severe in LPI group and can recover within two weeks. PAS progression and central corneal endothelium cell loss are not aggravated in 1 month after operation. PMID- 22321496 TI - [Alteration of anterior chamber and angle structure in eyes with primary angle closure after laser peripheral iridotomy]. AB - OBJECTIVE: To quantitatively evaluate the long-term changes in anterior segment morphology by using ultrasound biomicroscopy (UBM) after laser peripheral iridotomy (LPI) in eyes with primary angle closure (PAC). METHODS: This was a clinical case series study. A total of 54 eyes with PAC of 31 consecutive patients were enrolled. Routine ophthalmic and UBM examination were performed at visit one (before LPI), 2 weeks, 6, and 12 months after LPI. The parameters of anterior chamber were measured by UBM and calculated. Results of each follow-up time were analyzed using repeated measures analysis of variance. Parameters of UBM measurement at 750 um anterior to the sclera spur and at 500 um counterpart were compared using paired student t-test. RESULTS: Compared to before LPI, anterior chamber depth (ACD) was deepened by approximate 0.10 mm after LPI, however, it was not statistically significant (F = 3.50, P > 0.05). Angle opening distance (AOD), trabecular-iris angle (TIA), angle recess area (ARA) and trabecular-ciliary process distance (TCPD) were significantly increased at 2 weeks, 6 and 12 months after LPI compared with respective baseline [AOD750: (165.0 +/- 70.3), (185.8 +/- 68.5), (196.1 +/- 77.7) um vs (66.2 +/- 51.6) um, F = 92.60; TIA750: 14.1 degrees +/- 6.3 degrees , 15.5 degrees +/- 6.2 degrees , 16.4 degrees +/- 5.9 degrees vs 6.4 degrees +/- 4.9 degrees , F = 92.60; ARA: (0.058 +/- 0.024), (0.065 +/- 0.023), (0.068 +/- 0.026) mm(2) vs (0.025 +/- 0.017) mm(2), F = 92.60; TCPD: (647.1 +/- 113.0), (701.8 +/- 93.4), (670.1 +/- 95.4) um vs (571.0 +/- 97.2) um, F = 34.00; P < 0.05]. The parameters of UMB measurement at 750 um were significantly increased more than that at 500 um anterior to the sclera spur (AOD: t = 5.90, TIA750: t = 2.70, P < 0.05; ARA: t = 2.00, P = 0.05). CONCLUSIONS: LPI can significantly widen the peripheral anterior angle in eyes with PAC lasting for at least 1 year after LPI. Parameters detected by UBM at 750 um anterior to the sclera spur appear to be more sensitive in evaluating the alternation of peripheral angle structure. PMID- 22321497 TI - [The efficacy of low-energy selective laser trabeculoplasty]. AB - OBJECTIVE: To evaluate the efficacy of low-energy selective laser trabeculoplasty (SLT) in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OHT) following up to one year. METHODS: In this prospective clinical study, seventy-four eyes of seventy-four patients with OHT and POAG were enrolled. Thirty-nine patients received low-energy treatment using half of conventional laser energy and 100 spots over 360 degrees of the trabecular meshwork, while thirty-five patients received conventional laser energy as control. Intraocular pressure (IOP) and complications including conjunctival hyperemia and anterior uveitis were followed up at week 2, and month 1, 3, 6, and 12. Effective rate (reduction of IOP >= 20%) of treatment between the two groups and total rate of complications were analyzed by the chi-squared test. RESULTS: In OHT group, the effective rates of treatment were 81.81(9/11), 63.63 (7/11), 63.63 (7/11), 63.63 (7/11), and 45.45% (5/11) in the low-energy group and 50.00 (5/10), 70.0 (7/10), 60.0 (6/10), 40.0 (4/10), and 50.0% (5/10) in the control group, at weeks 2, month 1, 3, 6, and 12 after treatment respectively, while in POAG, the effective rates were 83.33 (15/18), 88.88 (16/18), 72.22 (13/18), 66.66 (12/18), and 44.44% (8/18) in the low-energy group and 84.21 (16/19), 73.68 (14/14), 57.89 (11/19), 57.89 (11/19) and 47.37% (9/19) in the control group at weeks 2, month 1, 3, 6, and 12 after treatment, respectively. There were no statistical difference between the low energy and conventional energy group at all time points in OHT (chi(2) = 2.386, 0.096, 1.173, 1.110, 0.043) and POAG (chi(2) = 0.005, 1.393, 0.833, 0.302, 0.032) group (P > 0.05). Complications were significantly (chi(2) = 4.299, P < 0.05) different between the two groups (eight eyes in the low-energy group on the day of treatment and fifteen eyes in the control group). Transient IOP spike (>= 3 mm Hg, 1 mm Hg = 0.133 kPa) occurred in three eyes (in the control group) on the day of treatment and partial peripheral anterior synechiae in one eye (in the control group) one month after treatment. CONCLUSIONS: Low energy SLT is as effective in lowering IOP with less complications compared with conventional laser energy SLT, which can be considered as an option for glaucoma therapy. PMID- 22321498 TI - [Clinical efficacy and safety of FP-7 Ahmed glaucoma valve implantation in neurovascular glaucoma patients]. AB - OBJECTIVE: To evaluate the efficacy and safety of FP-7 Ahmed glaucoma valves (AGV) implantation in neurovascular glaucoma (NVG) as the first choice of surgery. METHODS: This retrospective, comparative case series study collected a total of 36 eyes of 36 patients with neurovascular glaucoma who underwent AGV implantation in Zhongshan Ophthalmic Center from January 2009 to June 2010. Change of intraocular pressure (IOP), the best corrected visual acuity, numbers of anti-glaucoma medication, success rate and postoperative complications were followed up at day 1, week 1, month 1, and every 3 months after surgery. Complete success of surgery was rated as reduction of IOP >= 30% without medication and those who failed to meet criteria was rated as partial success. Data were analyzed by paired Student t-test for IOP, rank sum test for paired non parametric numbers of medication, and repeated measures analysis of variance for comparison of IOP between different time points using SPSS 13.0. RESULTS: Compared with pre-operation, IOP was significant (F = 9.26, P < 0.05) decreased after surgery with FP-7 AGV implantation (39.5 +/- 9.7) mm Hg (1 mm Hg = 0.133 kPa) vs (9.2 +/- 8.9), (11.8 +/- 3.8), (13.7 +/- 4.8), (16.9 +/- 5.3), (16.9 +/- 6.8) mm Hg at day 1, week 1, month 1, month 3 and the last following-up of post operation, respectively. The numbers of anti-glaucoma medication were significantly (Z = 6.764, P < 0.05) reduced from 4.0 (1-6) of pre-operation to 1.0 (1-3) of post-operation. At the last following up, the complete success rate after FP-7 AGV implantation was 80.6%, and qualified success rate was 91.7%. The postoperative complications including occlusion of the drainage tube, exposure of the drainage tube, shallow anterior chamber and encapsulated cystic blebs around the plate were controlled with additional treatment. CONCLUSIONS: The clinical outcome indicated that the implantation of FP-7 AGV has a stable IOP lowering effect and fewer complications, which can be considered as one of the first choices for management of NVG. PMID- 22321499 TI - [Assess correlation between bleb morphology at long-term intraocular pressure effect in primary angle-closure glaucoma following trabeculectomy]. AB - OBJECTIVE: To evaluate the correlation between morphologic appearance of blebs at 3 month and long-term intraocular pressure (IOP) effect in patients with primary angle-closure glaucoma (PACG) after trabeculectomy. METHODS: Multi-centered cases series. Data were collected from 176 patients aged >= 40 years with PACG who were participated in a randomized clinical trial that aimed at addressing the efficacy of augmented releasable sutures after trabeculectomy. The bleb morphology was graded using the Modified Indian Bleb Appearance Grading Scale (IBAGS) based on standard photos at 3 month after trabeculectomy. IOPs were measured with Goldmann applanation tonometer. The correlation between bleb components and other selected testing influencing factors and long-term IOP was tested by linear Logistic regression analysis. RESULTS: 150 patients (85.7%) completed 18 months of follow up. IOP was (15.6 +/- 5.4) mm Hg at 18 month of post-operation. 135 eyes had an IOP <= 21 mm Hg without additional medications, 10 eyes >= 21 mm Hg, and the remaining 5 eyes required one or two medications to maintain normal IOP. Using IBAGS system, bleb was graded in 142 eyes as follows: H(0) in 3 eyes, H(1) in 45 eyes, H(2) in 90 eyes, and H(3) in 4 eyes, while V(0) was observed in 66 eyes, V(1-3) in 76 eyes. IOP at 18 months in bleb with microcysts was 2.77 mm Hg lower (beta = -2.77, 95%CI = -0.46 to -5.08) than those without microcysts and in bleb with non-vascular was 2.07 mm Hg lower (beta = -2.07, 95%CI = -0.15 to -3.98) than those with vascular at 3 months after surgery. IOP was significantly (beta = -1.20, 95%CI: -0.00 to -2.40) decreased by 1.2 mm Hg with 10 years of age increase (P < 0.05). CONCLUSIONS: Early filtering bleb with microcysts, vascular, and age are identified as important factors to predict long-term IOP effect in patients with PACG after trabeculectomy but not early morphological appearance of filtering bleb. PMID- 22321500 TI - [Clinical evaluation on the coaxial 1.8 mm microincision cataract surgery]. AB - OBJECTIVE: To study and compare the outcomes of coaxial 1.8 mm microincision phacoemulsification with conventional coaxial 3 mm small-incision cataract surgery. METHODS: A randomized prospective study was conducted on 89 patients with age-related cataract: coaxial 1.8 mm microincision cataract surgery (MICS group) was performed in 45 cases (45 eyes), and coaxial 3 mm small-incision cataract surgery (SICS group) was performed in 44 cases (44 eyes). Statistical analysis was taken with the data of 40 cases (40 eyes) in the MICS group and 40 cases (40 eyes) in the SICS group. The average ultrasound power (AVE) and effective phacoemulsification time (EPT) were recorded during the operation. Visual acuity, endothelial cell density and cornea thickness were compared at intervals of 1 day, 1 week, 1 month and 3 months after surgery. In addition, surgically induced astigmatism (SIA) was analyzed. Statistic analysis was taken by student's t test and chi square test. RESULTS: There was no significant difference on AVE and EPT (P > 0.05) between these two groups. One day after the surgery, the MICS group showed better uncorrected visual acuity (0.16 +/- 0.14) as compared to the SICS group (0.23 +/- 0.12). The difference was statistically significant (P < 0.05). There were no significant differences on best corrected visual acuity, endothelial cell density and cornea thickness between these two groups. One week, 1 month and 3 months after the surgery, SIA was (0.62 +/- 0.28) D, (0.48 +/- 0.28) D, (0.47 +/- 0.25) D, (0.40 +/- 0.24) D in the MICS group, and (1.27 +/- 0.65) D, (1.18 +/- 0.59) D, (1.02 +/- 0.56) D, (0.79 +/- 0.48) D in the SICS group, respectively. The differences between the MIC and SICS groups were statistically significant (P < 0.01). SIA decreased significantly and became stable 1 week after surgery in MICS group, while the similar tendency appeared one month after the surgery in the SICS group. CONCLUSIONS: Coaxial 1.8 mm microincision cataract surgery could significantly reduce SIA and obtain more stable astigmatism status. This suggests that the coaxial MICS phacoemulsification surgery could get earlier visual rehabilitation postoperatively. PMID- 22321501 TI - [Clinical observation of visual quality after implantation of toric intraocular lens]. AB - OBJECTIVE: To observe the visual quality after implantation of Acrysof toric intraocular lens (IOL) in cataract patients. METHODS: Eighty eyes (60 patients) had implantation of Acrysof toric IOL in our hospital between Oct. 2009 and Sep. 2010. The patients were divided into four groups according to the toric models (T3, T4 and T5). The uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), residual cylinders, contrast sensitivity, high order aberration and IOL axis were evaluated preoperatively and 3 months postoperatively. Sixty five eyes (45 patients) had implantation of Acrysof Natural IOL. RESULTS: The UCVA improved in the toric groups three months postoperatively. The UCVA of group T5b was lower than that of the other three groups. The UCVA of toric group was (0.19 +/- 0.14) which was better than that of the control group (t = 4.04, P < 0.05). The residual cylinder was (1.69 +/- 0.68) D in group T5b, which was statistically different from the other three groups. The residual cylinder of the toric group was (0.51 +/- 0.78) D, which was much lower than the control group (t = 2.54, P < 0.05). The difference of contrast sensitivity between the four toric groups was not statistically significant. The low-order aberration and coma of group T5b was higher than that of the other three groups. The difference of contrast sensitivity between the toric group and the control group was not statistically significant. The low-order aberration and coma of the toric group were lower than those of the control group. The IOLs in 67 eyes (83.75%) rotated less than 5 degrees and all IOLs rotated less than 10 degrees. CONCLUSION: Implantation of the AcrySof toric IOL proves to be an effective, safe, and stable method of managing corneal astigmatism in cataract patients and provides good visual quality. PMID- 22321502 TI - [Analysis of optical coherence tomography in early stage of optic neuritis in multiple sclerosis patients]. AB - OBJECTIVE: To detect the changes in the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) in the eyes of multiple sclerosis patients during the early stage of optic neuritis. METHODS: A prospective case series study. Suspected acute optic neuritis of multiple sclerosis (MS) patients who attended the department of ophthalmology in Peking Union Medical College hospital from Feb. 2007 to Nov. 2010 were collected. Twenty two MS patients were evaluated within the first week of the attack of acute optic neuritis. The average thickness of RNFL and GCC was measured and a three dimensional image of optic disk was reconstructed using optical coherence tomography (OCT). RESULTS: Within the first week of onset, the average thickness of RNFL and GCC of first attack eyes increased 75% and 64%, respectively. The average thickness of RNFL and GCC in relapsed eyes decreased 91.7% and 62.5% respectively. The average thickness of RNFL and GCC of the fellow eyes also increased 60% and 43% respectively, within the first week of onset. More cases of optic disk edema and thickening of RNFL were found by OCT than by direct ophthalmoscopy. CONCLUSIONS: Different changes of the thickness of RNFL and GCC and morphology of the optic disk were detected during the early stage of the initial attack or relapsed optic neuritis in MS patients. OCT could detect such differences. PMID- 22321503 TI - [Analysis on characteristics of ocular trauma caused by military affairs in soldiers]. AB - OBJECTIVE: To investigate and analyze the epidemiological, clinical and prognostic characteristics of ocular trauma in soldiers caused by military affairs and compared with those in trauma caused by non-military causes. METHODS: A retrospective study on eye injury cases of military inpatients in 15 military general hospitals from 2001 to 2005 was performed and the data of 716 cases (772 eyes) were statistically analyzed. RESULTS: Three hundred and sixty inpatients (398 eyes) caused by military affairs accounted for 50.28% (360/716) of all military inpatients with eye injuries. The difference between trauma cases caused by military affairs and non-military affairs included: higher male/female ratio, 99.45% (358/360), 96.38% (343/356) (chi(2) = 6.92, P = 0.009) and younger age, averaged (23.14 +/- 5.23) yrs vs. (26.94 +/- 10.45) yrs (t = -6.163, P < 0.001). The most frequent causes in trauma caused by military affairs were explosion (12.78%, 46/360) and construction of national defense (12.78%, 46/360); whereas sports in leisure accounted for 35.96% cases in trauma caused by non-military affairs. The other characters of trauma caused by military affairs included: more non-mechanical globe injuries, 12.06% (48/398), 2.67% (10/374) (chi(2) = 23.12, P < 0.001), less mechanical injuries, 81.91% (326/398), 90.64% (339/374) (chi(2) = 11.59, P = 0.001); a higher proportion of open globe injuries (especially intraocular foreign body); more full-thickness laceration of globe wall needed primary repair, 57.26% (71/124), 84.78% (39/46) (chi(2) = 11.13, P = 0.001); higher rates of enucleation/evisceration, 4.52% (18/398), 1.07% (4/374), (chi(2) = 7.10, P = 0.008), lower vision, 15.33% (61/398), 4.81% (18/374) (chi(2) = 22.07, P < 0.001) and more blindness, 25.38% (101/398), 10.42% (39/374) (chi(2) = 28.03, P < 0.001); less eyes with final vision >= 0.5, 28.02% (111/396), 35.66% (133/373) (chi(2) = 4.81, P = 0.028) and less eyes with increasing vision, 68.68% (272/398), 76.41% (285/374) (chi(2) = 5.35, P = 0.021). CONCLUSIONS: Eye injury caused by military affairs is more severe and poorer in prognosis and is the direct factor that causing the decrease of military power. Emphasis should be placed on the prevention and treatment of eye injuries caused by military affairs. PMID- 22321504 TI - [Comparative clinical study of wavefront-guided laser in situ keratomileusis with versus without iris recognition for myopia or myopic astigmatism]. AB - OBJECTIVE: To explore the postoperative visual acuity results of wavefront-guided LASIK with iris recognition for myopia or myopic astigmatism and the changes of higher-order aberrations and contrast sensitivity function (CSF). METHODS: Series of prospective case studies, 158 eyes (85 cases) of myopia or myopic astigmatism were divided into two groups: one group underwent wavefront-guided LASIK with iris recognition (iris recognition group); another group underwent wavefront guided LASIK treatment without iris recognition through the limbus maring point (non-iris recognition group). To comparative analyze the postoperative visual acuity, residual refraction, the RMS of higher-order aberrations and CSF of two groups. RESULTS: There was no statistical significance difference between two groups of the average uncorrected visual acuity (t = 0.039, 0.058, 0.898; P = 0.844, 0.810, 0.343), best corrected visual acuity (t = 0.320, 0.440, 1.515; P = 0.572, 0.507, 0.218), and residual refraction [spherical equivalent (t = 0.027, 0.215, 0.238; P = 0.869, 0.643, 0.626), spherical (t = 0.145, 0.117, 0.038; P = 0.704, 0.732, 0.845) and cylinder (t = 1.676, 1.936, 0.334; P = 0.195, 0.164, 0.563)] at postoperative 10 days, 1 month and 3 month. The security index of iris recognition group at postoperative 3 month was 1.06 and non-iris recognition group was 1.03; the efficacy index of iris recognition group is 1.01 and non-iris recognition group was 1.00. Postoperative 3 month iris recognition group 93.83% eyes and non-iris recognition group of 90.91% eyes spherical equivalent within +/ 0.50 D (chi(2) = 0.479, P = 0.489), iris recognition group of 98.77% eyes and non-iris recognition group of 97.40% eyes spherical equivalent within +/- 1.00 D (Fisher test, P = 0.613). There was no significance difference between the two groups of security, efficacy and predictability. Non-iris recognition group postoperative 1 month and postoperative 3 months 3-order order aberrations root mean square value (RMS) higher than the iris recognition group increased (t = 3.414, -2.870; P = 0.027, 0.045), in particular of coma; the general higher-order aberrations (t = 0.386, 1.132; P = 0.719, 0.321), 4-order aberrations (t = 0.808, 2.720; P = 0.464, 0.063), and 5-order aberrations (t = 0.148, -1.717; P = 0.890, 0.161) show no statistically significant difference. Three months after surgery, two groups have recovered at all spatial frequencies of CSF, iris recognition group at 3.0 c/d (t = 3.209, P = 0.002) and 6.0 c/d (t = 2.997, P = 0.004) spatial frequencies of CSF under mesopic condition was better than non-iris recognition group, glare contrast sensitivity function (GCSF) for 3.0 c/d (t = 3.423, P = 0.001) and 6.0 c/d (t = 6.986, P = 0.000) spatial frequencies under mesopic condition and 1.5 c/d (t = 9.839, P = 0.000) and 3.0 c/d (t = 7.367, P = 0.000) spatial frequencies under photopic condition in iris recognition group were better than non-iris recognition group, there were no significant difference between two groups at the other spatial frequencies. CONCLUSIONS: Wavefront guided LASIK with or without iris recognition both acquired better postoperative visual acuity, but in comparison with without iris recognition, wavefront-guided LASIK with iris recognition is efficient to reduce coma and enhance contrast sensitivity of postoperative. PMID- 22321505 TI - [Effects of single mode's high-order aberrations on visual acuity corrected using adaptive optics technique]. AB - OBJECTIVE: To analyze the effects of single mode's high-order aberration on visual acuity in real time dynamically corrected using adaptive optics technique. METHODS: Control study. In a dark room, twelve young healthy volunteers were administrated with 5 g/L phenylephrine to fully dilate the right eye's pupil to a diameter over 6 mm. The subjects' myopia and astigmatism were fully corrected using optical lenses. Coma, trefoil, spherical aberration and other forth-order aberrations except for spherical aberration were corrected using adaptive optics, and 100% contrast visual acuity was simultaneously measured. RESULTS: All single mode's high-order aberrations were fully corrected, whereas other aberrations remained unchanged. Mean visual acuity of subjects was improved by 0.021 LogMAR, 0.017 LogMAR, 0.022 LogMAR and 0.025 LogMAR after correction of coma, trefoil, spherical aberration and other forth-order aberrations except for spherical aberration, respectively. Ratio of change in visual acuity was (-0.40 +/- 1.22) LogMAR/um, (-0.20 +/- 0.61) LogMAR/um, (-0.80 +/- 1.44) LogMAR/um and (-0.30 +/- 0.57) LogMAR/um, respectively. There was a linear correlation between visual acuity after correction of single mode's different high-order aberrations and RMS of residual aberrations (R(2) = 0.13, P < 0.01). CONCLUSION: Among high-order aberrations in normal human eye, spherical aberration generates a most impact on visual acuity, followed by coma, other forth-order aberrations except for spherical aberration and trefoil. A linear correlation was found between change in visual acuity and RMS of residual aberrations. PMID- 22321506 TI - [Research on retinoic acid signals in retina of guinea pig eyes with different monochromatic illumination]. AB - OBJECTIVE: Retinoic acid (RA) is the only extrinsic biochemical candidate that could act as a growth controller, the present study was designed to evaluate the retinoic acid signals in retina of guinea pig eyes with different monochromatic illumination. METHODS: Ninety 2-week-old guinea pigs were divided into 3 groups randomly and were raised under green (530 nm) (n = 30), blue (430 nm) (n = 30) or white lighting (5000K) (n = 30) conditions. The axial length was measured with Cine scan A/B ultrasonography before, 2 weeks, 4 weeks, 8 weeks during experiment. After the biometrical measurement finished, 9 guinea pigs were sacrificed randomly in each group and retina was dissected. The RA level in retina was detected by High Performance Liquid Chromatography (HPLC). The expressions of retinoic acid-binding proteins I (CRABP-I) and retinoic acid receptor-beta (RAR-beta) protein and mRNA were assayed by Western-blot and Real time PCR, respectively. The experiment and use of animals followed the Standard of Association for Research in Vision and Ophthalmology. RESULTS: 1. The axial length among the three groups showed a significant difference at 4 weeks during experiment (F = 3.946; P < 0.05), the green lighting group showed the fastest growing, the axial length of the three groups are (8.36 +/- 0.11) mm (green), (7.88 +/- 0.49) mm (blue), 7.98 +/- 0.32 mm (white) respectively at 8 weeks during experiment; 2. The RA levels demonstrated a same trend with the axial length, at 8 weeks during experiment the RA levels are 4.846 +/- 0.56 ug/g (green), 3.583 +/- 0.26 ug/g (blue), 4.419 +/- 0.36 ug/g (white) respectively; 3. Changes of the expression of CRABP-I and RAR-beta occurred at different times, a significant difference of RAR-beta among three groups appeared earlier, the green lighting group showed a highest level. CONCLUSION: The different levels of retinoic acid signals were showed in retina of guinea pig eyes under different monochromatic illumination. The eye growth was significantly faster in green group than in blue group and white group, meanwhile, the RA level, the expressions of CRABP-I and RAR-beta in the retina were higher in green group than the other two groups. These findings suggest that RA may act as a messenger in eye growth promoted by different monochromatic illumination. PMID- 22321507 TI - [Epidemiology and classification of primary angle-closure glaucoma today]. AB - Primary angle-closure glaucoma (PACG) is an independent and complex disease. According to International Society Geographical & Epidemiological Ophthalmology (ISGEO) PACG is defined as primary angle closure (PAC) with glaucomatous neuropathy, whereas a diagnosis of PAC will be given to patients without a neuropathy. This classification is simple and very useful in survey. In contrast, conventional classification of PACG by Chinese Glaucoma Association is based on anatomical predisposition, such as peripheral iridocorneal apposition/adhesions, and functional sub-stages, which is more clinical usefulness. The difference of PACG classification system between Chinese Glaucoma Association and ISGEO appears to hinder the communication and cooperation between Chinese and international colleague. In this article, we attempted to review classifications and analyze the epidemiological characteristics of PACG under these two systems. It is obvious that the continuing effects to establish a rational and standardized classification system of PACG will greatly promote and benefit glaucoma research and clinical practice for both international and domestic ophthalmic community. PMID- 22321508 TI - [The progress of aqueous humor outflow pathway in open-angle glaucoma]. AB - Primary open angle glaucoma (POAG) is defined as an optic neuropathy characterized by loss of optic nerve axons and retinal ganglion cells. Increase of intraocular pressure (IOP) is a major risk factor for POAG, which is partially due to an abnormally high aqueous humor outflow resistance in trabecular meshwork (TM). Trabecular outflow pathway is a key element in drainage of aqueous humor. Malfunction of TM in POAG is associated with over expression of inflammatory markers, cellular senescence, oxidative stress, and decrease of cellularity. The biological changes of TM cell and extracellular matrix compromise trabecular pathway drainage resulting in an increased IOP. This article reviewed the progression in research on aqueous humor outflow pathway emphasizing the alteration of trabecular pathway. PMID- 22321509 TI - Increasing peptide identifications and decreasing search times for ETD spectra by pre-processing and calculation of parent precursor charge. AB - BACKGROUND: Electron Transfer Dissociation [ETD] can dissociate multiply charged precursor polypeptides, providing extensive peptide backbone cleavage. ETD spectra contain charge reduced precursor peaks, usually of high intensity, and whose pattern is dependent on its parent precursor charge. These charge reduced precursor peaks and associated neutral loss peaks should be removed before these spectra are searched for peptide identifications. ETD spectra can also contain ion-types other than c and z. Modifying search strategies to accommodate these ion-types may aid in increased peptide identifications. Additionally, if the precursor mass is measured using a lower resolution instrument such as a linear ion trap, the charge of the precursor is often not known, reducing sensitivity and increasing search times. We implemented algorithms to remove these precursor peaks, accommodate new ion-types in noise filtering routine in OMSSA and to estimate any unknown precursor charge, using Linear Discriminant Analysis [LDA]. RESULTS: Spectral pre-processing to remove precursor peaks and their associated neutral losses prior to protein sequence library searches resulted in a 9.8% increase in peptide identifications at a 1% False Discovery Rate [FDR] compared to previous OMSSA filter. Modifications to the OMSSA noise filter to accommodate various ion-types resulted in a further 4.2% increase in peptide identifications at 1% FDR. Moreover, ETD spectra when searched with charge states obtained from the precursor charge determination algorithm is shown to be up to 3.5 times faster than the general range search method, with a minor 3.8% increase in sensitivity. CONCLUSION: Overall, there is an 18.8% increase in peptide identifications at 1% FDR by incorporating the new precursor filter, noise filter and by using the charge determination algorithm, when compared to previous versions of OMSSA. PMID- 22321510 TI - Arsenic mobilizes Langerhans cell migration and induces Th1 response in epicutaneous protein sensitization via CCL21: a plausible cause of decreased Langerhans cells in arsenic-induced intraepithelial carcinoma. AB - Arsenic, still a significant environmental threat in several regions in the world, induces various cancers, including lungs, skin, and bladder. Arsenic induced Bowen's disease (As-BD) is generally an indolent cutaneous intraepithelial carcinoma in susceptible people. Patients with As-BD have been found to have attenuated contact hypersensitivity. Skin samples collected from these patients have reduced numbers of Langerhans cells (LCs), the major epidermal antigen presenting cells expressing Langerins. This study uses an epicutaneous protein sensitization model to investigate the mechanism through which LCs are decreased in As-BD. It further investigates the possibility that arsenic alters LC migration and polarizes Th responses. To do this, we patch sensitized Balb/c mice or DT-treated Langerin-DTR mice (conditional depletion of Langerin(+) cells) with OVA or PBS, and fed them water containing 300 ppb arsenic or regular water for 200 MUl for five days. Ninety-six hours after OVA sensitization, Langerin(+)EpCAM(+) cells in arsenic-treated WT mice were significantly increased in draining lymph nodes and decreased in epidermis without changes in the dermis. Lymph node cells from arsenic-treated WT mice were found to proliferate more than lymph node cells from control PBS-treated mice after OVA challenge in vitro. They also secreted more IFN-gamma and IL-12, but not IL-4, IL-13, or IL-17. However, cell proliferation and the induction of IFN gamma by arsenic were found to be abolished in DT-treated Langerin-DTR mice. The expressions of CCL21 and CXCL12 were also increased in lymph nodes from arsenic treated WT mice. The administration of a neutralizing antibody against CCL21, but not CXCL12, abolished the increase of LCs in lymph nodes in vivo. The results of this study, the first to study oral arsenic polarization of Th1 responses in epicutaneous protein sensitization through CCL21-mediated LC migration, suggest the chronicity of As-BD without invasion might result from enhanced Th1 responses and altered LC migrations by arsenic. PMID- 22321511 TI - Thiostrepton is an inducer of oxidative and proteotoxic stress that impairs viability of human melanoma cells but not primary melanocytes. AB - Pharmacological induction of oxidative and proteotoxic stress has recently emerged as a promising strategy for chemotherapeutic intervention targeting cancer cells. Guided by a differential phenotypic drug screen for novel lead compounds that selectively induce melanoma cell apoptosis without compromising viability of primary human melanocytes, we have focused on the cyclic pyridinyl polythiazolyl peptide-antimicrobial thiostrepton. Using comparative gene expression-array analysis, the early cellular stress response induced by thiostrepton was examined in human A375 metastatic melanoma cells and primary melanocytes. Thiostrepton displayed selective antimelanoma activity causing early induction of proteotoxic stress with massive upregulation of heat shock (HSPA6, HSPA1A, DNAJB4, HSPB1, HSPH1, HSPA1L, CRYAB, HSPA5, DNAJA1), oxidative stress (HMOX1, GSR, SOD1), and ER stress response (DDIT3) gene expression, confirmed by immunodetection (Hsp70, Hsp70B', HO-1, phospho-eIF2alpha). Moreover, upregulation of p53, proapoptotic modulation of Bcl-2 family members (Bax, Noxa, Mcl-1, Bcl 2), and induction of apoptotic cell death were observed. Thiostrepton rapidly induced cellular oxidative stress followed by inactivation of chymotrypsin-like proteasomal activity and melanoma cell-directed accumulation of ubiquitinated proteins, not observed in melanocytes that were resistant to thiostrepton-induced apoptosis. Proteotoxic and apoptogenic effects were fully antagonized by antioxidant intervention. In RPMI 8226 multiple myeloma cells, known to be exquisitely sensitive to proteasome inhibition, early proteotoxic and apoptogenic effects of thiostrepton were confirmed by array analysis indicating pronounced upregulation of heat shock response gene expression. Our findings demonstrate that thiostrepton displays dual activity as a selective prooxidant and proteotoxic chemotherapeutic, suggesting feasibility of experimental intervention targeting metastatic melanoma and other malignancies including multiple myeloma. PMID- 22321512 TI - Molecular evidence of host influences on the evolution and spread of human tapeworms. AB - The taeniasis/cysticercosis complex is included in the list of neglected zoonotic diseases by the World Health Organization due to its significant impact on public health in tropical areas. Cysticercosis is still endemic in many regions of Asia, Africa and Latin America. Long absent in Europe and in other developed countries, cysticercosis has recently re-emerged in the United States and Canada, due to immigration, travel and local transmission. This has encouraged the use of molecular data to understand better the influence of animal and human hosts on the emergence and spread of Taenia species. The increasing number of mitochondrial sequences now available from human tapeworms and recent advances in computational tools has enabled reconstruction of the biogeography and evolutionary history of these organisms. New molecular data have provided insights into the biogeography of T. solium, T. asiatica and T. saginata. A Bayesian statistical framework using variable evolutionary rates from lineage to lineage has allowed an improved timescale analysis of human tapeworms. The dates of divergence obtained were compared to the timing of evolutionary events in the history of their hosts, based on the hypothesis that Taenia spp. and their hosts share a common history. Herein, we review changes in the definitive and secondary hosts and human interactions that underlie the differentiation and evolution of tapeworms. Species diversification of Taenia seems to be closely linked with the evolution of intermediate hosts in response to climatic events during the Pleistocene. Different genotypes of T. solium emerged when European and Asian wild boar Sus spp. populations diverged. Taenia saginata emerged when wild cattle Bos primigenius evolved and when zebu Bos indicus and taurine Bos taurus ancestors separated. Humans through migrations and later with the development of farming and animal husbandry may have had a significant impact on the spread and diversification of tapeworms. Migrations of Homo erectus from Africa to Asia and later of Homo sapiens facilitated the diversification and dispersal of T. solium and T. saginata populations. The development of animal husbandry, making Sus scrofa and Bos taurus preferential intermediate hosts, led to the worldwide distribution of parasites. New molecular data combined with an innovative dating method allow us to explain the ways in which ancient human migrations promoted the emergence and spread of taeniasis and cysticercosis around the world. Another intriguing phenomenon explained better by our approach is the influence of human settlement on the spread of these parasites in recently inhabited areas. The diverse nature of T. solium currently observed in Madagascar may correspond to multiple imports of the parasite during Austronesian migrations, while in Mexico a recent influence of humans during the colonial period is more likely. Human activities, especially food preparation and husbandry methods, remain responsible for the transmission and persistence of these parasites. PMID- 22321513 TI - Kinematics of walking in the hermit crab, Pagurus pollicarus. AB - Hermit crabs are decapod crustaceans that have adapted to life in gastropod shells. Among their adaptations are modifications to their thoracic appendages or pereopods. The 4th and 5th pairs are adapted for shell support; walking is performed with the 2nd and 3rd pereopods, with an alternation of diagonal pairs. During stance, the walking legs are rotated backwards in the pitch plane. Two patterns of walking were studied to compare them with walking patterns described for other decapods, a lateral gait, similar to that in many brachyurans, and a forward gait resembling macruran walking. Video sequences of free walking and restrained animals were used to obtain leg segment positions from which joint angles were calculated. Leading legs in a lateral walk generated a power stroke by flexion of MC and PD joints; CB angles often did not change during slow walks. Trailing legs exhibited extension of MC and PD with a slight levation of CB. The two joints, B/IM and CP, are aligned at 90 degrees angles to CB, MC and PD, moving dorso-anteriorly during swing and ventro-posteriorly during stance. A forward step was more complex; during swing the leg was rotated forward (yaw) and vertically (pitch), due to the action of TC. At the beginning of stance, TC started to rotate posteriorly and laterally, CB was depressed, and MC flexed. As stance progressed and the leg was directed laterally, PD and MC extended, so that at the end of stance the dactyl tip was quite posterior. During walks of the animal out of its shell, the legs were extended more anterior-laterally and the animal often toppled over, indicating that during walking in a shell its weight stabilized the animal. An open chain kinematic model in which each segment was approximated as a rectangular solid, the dimensions of which were derived from measurements on animals, was developed to estimate the CM of the animal under different load conditions. CM was normally quite anterior; removal of the chelipeds shifted it caudally. Application of forces simulating the weight of the shell on the 5th pereopods moved CM just anterior to the thoracic-abdominal junction. However, lateral and vertical coordinates were not altered under these different load conditions. The interaction of the shell aperture with proximal leg joints and with the CM indicates that the oblique angles of the legs, due primarily to the rotation of the TC joints, is an adaptation that confers stability during walking. PMID- 22321514 TI - Novel microbial route to synthesize ZnO nanoparticles using Aeromonas hydrophila and their activity against pathogenic bacteria and fungi. AB - In the present work, we describe a low-cost, unreported and simple procedure for biosynthesis of zinc oxide nanoparticles (ZnO NPs) using reproducible bacteria, Aeromonas hydrophila as eco-friendly reducing and capping agent. UV-vis spectroscopy, XRD, FTIR, AFM, NC-AFM and FESEM with EDX analyses were performed to ascertain the formation and characterization of ZnO NPs. The synthesized ZnO NPs were characterized by a peak at 374 nm in the UV-vis spectrum. XRD confirmed the crystalline nature of the nanoparticles and AFM showed the morphology of the nanoparticle to be spherical, oval with an average size of 57.72 nm. Synthesized ZnO NPs showed the XRD peaks at 31.75 degrees , 34.37 degrees , 47.60 degrees , 56.52 degrees , 66.02 degrees and 75.16 degrees were identified as (100), (002), (101), (102), (110), (112) and (202) reflections, respectively. Rietveld analysis to the X-ray data indicated that ZnO NPs have hexagonal unit cell at crystalline level. The size and topological structure of the ZnO NPs was measured by NC-AFM. The morphological characterization of synthesized nanoparticles was analyzed by FESEM and chemical composition by EDX. The antibacterial and antifungal activity was ended with corresponding well diffusion and minimum inhibitory concentration. The maximum zone of inhibition was observed in the ZnO NPs (25 MUg/mL) against Pseudomonas aeruginosa (22+/-1.8 mm) and Aspergillus flavus (19+/-1.0 mm). Bacteria-mediated ZnO NPs were synthesized and proved to be a good novel antimicrobial material for the first time in this study. PMID- 22321515 TI - A new polymerizable fluorescent PET chemosensor of fluoride (F-) based on naphthalimide-thiourea dye. AB - A novel N-allyl-4-amino-substituted 1,8-naphthalimide dye, containing thiourea functional group with intense yellow-green fluorescence was successfully synthesized. Copolymerization was done with styrene. The photophysical characteristics of dye and its copolymer in solution and solid film were investigated in the presence of halide ions. The results reveal that the fluorescence emissions of the monomer dye and also its polymer were 'switched off' in the presence of fluoride ions. The dye showed spectral shifts and intensity changes in the presence of more fluoride ions which lead to detect certain fluoride concentrations of 10-150 mM at visible wavelengths. By adding the fluoride ions, green-yellow to purple color changes occurs and the green fluorescence emission quenches, all of which easily observed by naked eyes. These phenomena are essential for producing a dual responsive chemosensor for fluoride ions. The polymeric sensor, in the film state exhibited a fast response to the fluoride ions. PMID- 22321516 TI - Prevalence of types of methicillin-resistant Staphylococcus aureus in turkey flocks and personnel attending the animals. AB - Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) have been isolated from a number of livestock species and persons involved in animal production. We investigated the prevalence of LA-MRSA in fattening turkeys and people living on farms that house fattening turkeys. Eighteen (90%) of 20 investigated flocks were positive for MRSA, and on 12 of the farms 22 (37.3%) of 59 persons sampled were positive for MRSA. People with frequent access to the stables were more likely to be positive for MRSA. In most flocks MRSA that could be assigned to clonal complex (CC) 398 were detected. In five flocks MRSA of spa type t002 that is not related to CC398 were identified. Moreover, other methicillin-resistant Staphylococcus spp. were detected on 11 farms and in eight people working on the farms. PMID- 22321517 TI - Early outcomes of bariatric surgery in patients with metabolic syndrome: an analysis of the bariatric outcomes longitudinal database. AB - BACKGROUND: Metabolic syndrome (MetS) complicating obesity is endemic in the United States. STUDY DESIGN: Bariatric Outcomes Longitudinal Database, the national database for the American Society for Metabolic and Bariatric Surgery Bariatric Surgery Center of Excellence Program, was queried to identify patients undergoing bariatric surgery from June 2007 through November 2010. MetS was defined as the presence of hypertension, diabetes, and dyslipidemia at presentation for bariatric surgery. Ninety-day and 1-year outcomes were assessed to determine early outcomes in bariatric surgery patients with MetS. RESULTS: Among 186,576 research-consented patients, 23,106 (12%) were diagnosed with MetS. Patients with MetS were more likely to be male (35% vs 20%; p < 0.0001), older (mean age 54 vs 44 years; p < 0.0001), and Caucasian (81% vs 74%; p < 0.0001). Of the 23,106 MetS patients, more underwent gastric bypass (RYGB) (62%) compared with gastric banding (32%), sleeve gastrectomy (4.5%), and biliopancreactic diversion with duodenal switch (BPD/DS)(1.5%). MetS patients had an increase in serious complications (2.4% vs 1.0%; p < 0.0001), readmissions (6.2% vs 4.7%; p < 0.0001), and mortality (0.3% vs 0.1%; p < 0.0001) within 90 days of operation. After adjusting for sex, age, and body mass index, RYGB patients with MetS had an increased risk of 90-day serious complications compared to RYGB patients without MetS (odds ratio 1.43; 95% CI, 1.27 to 1.61; p < 0.0001). The 12-month remission rate of diabetes was least for gastric banding (28%) compared with the other procedures (RYGB 62%, sleeve gastrectomy 52%, BPD/DS 74%). CONCLUSIONS: Patients with MetS undergoing bariatric surgery showed dramatic improvement in diabetes 1 year after surgery; however, an adverse 90-day outcome was more common. PMID- 22321518 TI - A progressive postresection walking program significantly improves fatigue and health-related quality of life in pancreas and periampullary cancer patients. AB - BACKGROUND: As patients with pancreas and periampullary cancer (PPC) experience improved survival rates and longevity, the focus shifts toward living life while surviving cancer. Fatigue is the most commonly reported symptom in all cancer patients. Exercise has been found to effectively decrease fatigue levels and improve physical functioning in cancer patients. STUDY DESIGN: One hundred two patients with resected PPC consented to participate in this study and were randomized to either an intervention group (IG) or a usual care group (UCG). Subjects completed visual analog scales, the FACIT-Fatigue Scale and the Short Form-36v2 after surgery and again 3 to 6 months after hospital discharge. RESULTS: Patients in the IG and UCG were comparable with regard to demographics, comorbidities, cancer type and staging, type of resection, preoperative fatigue and pain levels, adjuvant therapy, and baseline walking distance. Patients in the IG had significantly improved scores on the FACIT-Fatigue Scale at study completion, improved fatigue and pain scores, as well as overall physical functioning and mental health composite scores. At study completion, participants in the IG were walking twice as far and were significantly more likely to have continued walking or another form of exercise as compared with the UCG. Using hierarchical cluster analysis, 3 mutually exclusive symptom groupings were identified in the cohort. Kaplan-Meier survival analysis did not indicate an overall survival benefit for the IG. CONCLUSIONS: This is the first prospective, randomized controlled trial to report that participation in a home walking program confers a significant benefit in resected PPC patients with regard to fatigue levels, physical functioning, and health-related quality of life. PMID- 22321519 TI - Tort reform is associated with more medical board complaints and disciplinary actions. AB - BACKGROUND: Previous reports have confirmed that comprehensive tort reform in Texas (enacted in 2003) was associated with fewer lawsuits and less litigation associated cost. We hypothesized that complaints to the Texas Medical Board (TMB) increased after tort reform. STUDY DESIGN: To test this hypothesis, we compared complaints, investigations, disciplinary actions, and penalties against physicians before and after comprehensive state tort reform measures were adopted. Data were obtained from the TMB for a 15-year period (1996 to 2010). RESULTS: When comparing the period before tort reform (1996 to 2002) with the period after tort reform (2004 to 2010), TMB complaints increased 13%; investigations opened increased 33%, disciplinary actions increased 96%, license revocations or surrenders increased 47%, and financial penalties increased 367%. All of these increases were statistically significant (p <= 0.01). CONCLUSIONS: After tort reform in Texas, the total number of complaints, investigations, disciplinary decisions, license revocations or surrenders, and financial penalties from the TMB significantly increased. In Texas, tort reform was accompanied by legislatively directed, enhanced oversight and activity of the authority (TMB) charged with regulation of the medical profession. PMID- 22321520 TI - Regulated hepatic reperfusion mitigates ischemia-reperfusion injury and improves survival after prolonged liver warm ischemia: a pilot study on a novel concept of organ resuscitation in a large animal model. AB - BACKGROUND: Ischemia-reperfusion injury (IRI) can occur during hepatic surgery and transplantation. IRI causes hepatic mitochondrial and microcirculatory impairment, resulting in acute liver dysfunction and failure. We proposed a novel strategy of regulated hepatic reperfusion (RHR) to reverse the cellular metabolic deficit that incurred during organ ischemia by using a substrate-enriched, oxygen saturated, and leukocyte-depleted perfusate delivered under regulated reperfusion pressure, temperature, and pH. We investigate the use of RHR in mitigating IRI after a prolonged period of warm ischemia. METHODS: Using a 2-hour liver warm ischemia swine model, 2 methods of liver reperfusion were compared. The control group (n = 6) received conventional reperfusion with unmodified portal venous blood under unregulated reperfusion pressure, temperature, and pH. The experimental group (n = 6) received RHR. We analyzed the effects of RHR on post reperfusion hemodynamic changes, liver function, and 7-day animal survival. RESULTS: RHR resulted in 100% survival compared with 50% in the control group (p = 0.05). Post-reperfusion syndrome was not observed in the RHR group, but it occurred in 83% of the control group. RHR resulted in a lesser degree of change from baseline serum alanine aminotransferase levels, aspartate aminotransferase, and lactate dehydrogenase after reperfusion compared with the control group. Histopathologic evaluation showed minimal ischemic changes in the RHR group, whereas a considerable degree of coagulative hepatocellular necrosis was observed in the control group. CONCLUSIONS: Regulated hepatic reperfusion mitigates IRI, facilitates liver function recovery, and improves survival after a prolonged period of hepatic warm ischemia. This novel strategy has potential applicability to clinical hepatic surgery and liver transplantation when marginal grafts are used. PMID- 22321522 TI - Adherence to a simplified management algorithm reduces morbidity and mortality after penetrating colon injuries: a 15-year experience. AB - BACKGROUND: Our previous experience with colon injuries suggested that operative decisions based on a defined algorithm improve outcomes. The purpose of this study was to evaluate the validity of this algorithm in the face of an increased incidence of destructive injuries observed in recent years. STUDY DESIGN: Consecutive patients with full-thickness penetrating colon injuries over an 8 year period were evaluated. Per algorithm, patients with nondestructive injuries underwent primary repair. Those with destructive wounds underwent resection plus anastomosis in the absence of comorbidities or large pre- or intraoperative transfusion requirements (more than 6 units packed RBCs); otherwise they were diverted. Outcomes from the current study (CS group) were compared with those from the previous study (PS group). RESULTS: There were 252 patients who had full thickness penetrating colon injuries: 150 (60%) patients had nondestructive colon wounds treated with primary repair and 102 patients (40%) had destructive wounds (CS). Demographics and intraoperative transfusions were similar between CS and PS groups. Of the 102 patients with destructive injuries, 75% underwent resection plus anastomosis and 25% underwent diversion. Despite more destructive injuries managed in the CS group (41% vs 27%), abscess rate (18% vs 27%) and colon-related mortality (1% vs 5%) were lower in the CS. Suture line failure was similar in CS compared with PS (5% vs 7%). Adherence to the algorithm was >90% in the CS (similar to PS). CONCLUSIONS: Despite an increase in the incidence of destructive colon injuries, our management algorithm remains valid. Destructive injuries associated with pre- or intraoperative transfusion requirements of more than 6 units packed RBCs and/or significant comorbidities are best managed with diversion. By managing the majority of other destructive injuries with resection plus anastomosis, acceptably low morbidity and mortality can be achieved. PMID- 22321521 TI - Influence of the National Trauma Data Bank on the study of trauma outcomes: is it time to set research best practices to further enhance its impact? AB - BACKGROUND: Risk-adjusted analyses are critical in evaluating trauma outcomes. The National Trauma Data Bank (NTDB) is a statistically robust registry that allows such analyses; however, analytical techniques are not yet standardized. In this study, we examined peer-reviewed manuscripts published using NTDB data, with particular attention to characteristics strongly associated with trauma outcomes. Our objective was to determine if there are substantial variations in the methodology and quality of risk-adjusted analyses and therefore, whether development of best practices for risk-adjusted analyses is warranted. STUDY DESIGN: A database of all studies using NTDB data published through December 2010 was created by searching PubMed and Embase. Studies with multivariate risk adjusted analyses were examined for their central question, main outcomes measures, analytical techniques, covariates in adjusted analyses, and handling of missing data. RESULTS: Of 286 NTDB publications, 122 performed a multivariable adjusted analysis. These studies focused on clinical outcomes (51 studies), public health policy or injury prevention (30), quality (16), disparities (15), trauma center designation (6), or scoring systems (4). Mortality was the main outcome in 98 of these studies. There were considerable differences in the covariates used for case adjustment. The 3 covariates most frequently controlled for were age (95%), Injury Severity Score (85%), and sex (78%). Up to 43% of studies did not control for the 5 basic covariates necessary to conduct a risk adjusted analysis of trauma mortality. Less than 10% of studies used clustering to adjust for facility differences or imputation to handle missing data. CONCLUSIONS: There is significant variability in how risk-adjusted analyses using data from the NTDB are performed. Best practices are needed to further improve the quality of research from the NTDB. PMID- 22321523 TI - Bevacizumab-associated fistula formation in postoperative colorectal cancer patients. AB - BACKGROUND: Adjuvant chemotherapy regimens for metastatic colorectal cancer (CRC) routinely include bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF). We have identified a correlation between bevacizumab and fistula formation after resection of advanced CRC. STUDY DESIGN: Patients undergoing treatment with bevacizumab for metastatic CRC after 2005 were identified and reviewed. Of 222 consecutive patients, 9 patients treated with bevacizumab subsequently developed fistulas. These patients' charts were reviewed with attention to diagnosis, timing of operation relative to bevacizumab therapy, location of fistula, and fistula treatment. RESULTS: Of the 9 identified patients (9 of 222, 4.1%), 6 had rectal cancer, 2 had colon cancer, and 1 had synchronous CRC. Fistulas were most commonly anal or perineal (6 of 9, 66.7%) and colovesicular (3 of 9, 33%). On average, bevacizumab was initiated 23.6 months after the initial operation; complications occurred 3.9 months after starting bevacizumab. Nearly uniformly, cessation of bevacizumab led to fistula healing; however, 3 patients (33%) required fecal diversion. CONCLUSIONS: Bevacizumab is the most common antiangiogenesis agent used for treatment of metastatic CRC. Previous adverse events associated with bevacizumab treatment include venous thromboembolism, poor wound healing, and spontaneous bowel perforation. In this report, late postoperative development of fistulas occurred relatively soon after initiation of bevacizumab and usually spontaneously resolved with cessation of bevacizumab treatment. Based on the timing of fistula development relative to operation and initiation of bevacizumab, fistulas are likely secondary to bevacizumab therapy rather than postsurgical complications. Bevacizumab-induced fistulas occur in a small, but significant proportion of CRC patients and must be recognized early. PMID- 22321524 TI - What happens to racial and ethnic minorities after cancer surgery at American College of Surgeons National Surgical Quality Improvement Program hospitals? AB - BACKGROUND: Inadequate access has contributed to widespread racial disparities in cancer care in the United States. However, the outcomes for racial minorities at quality-seeking hospitals, such as those participating in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP), remain unknown. We hypothesized that operative outcomes for racial and ethnic minority patients after cancer surgery at ACS NSQIP hospitals are comparable with those for white patients. STUDY DESIGN: Using the 2005-2008 ACS NSQIP data, we identified 38,926 patients who underwent thoracic, abdominal, or pelvic cancer surgery. We used multivariate logistic regression to examine the association between race and ethnicity and short-term (30-day) operative outcomes after cancer surgery. Sensitivity analyses were performed to ensure the relationship remained consistent after stratification by procedure. RESULTS: Nonwhite patients constituted 16.9% of patients treated for cancer surgery in ACS NSQIP hospitals. Although nonwhite patients were more likely to have higher levels of comorbidities and undergo more complex resections (p < 0.05 for all), multivariate analyses demonstrated that these patients were as likely as white patients to have adverse short-term operative outcomes develop after cancer surgery. These results persisted after stratification by extent of surgical procedure. However, black, Hispanic, and American-Indian/Alaskan-Native patients were more likely to experience prolonged length of stay (odds ratio for black vs white patients = 1.33; p < 0.001). CONCLUSIONS: Racial and ethnic minority patients who undergo their cancer surgery at ACS NSQIP hospitals have short-term operative outcomes similar to white patients, but they remain hospitalized longer. These findings suggest that access to quality-driven hospitals might ameliorate racial disparities in cancer care and outcomes. Future policies should focus on expanding access to quality-driven surgical facilities as a step toward timely and optimal cancer care. PMID- 22321525 TI - Diagnoses influence surgical site infections (SSI) in colorectal surgery: a must consideration for SSI reporting programs? AB - BACKGROUND: Colorectal surgery is associated with high rates of surgical site infection (SSI). The National Surgery Quality Improvement Program is a validated, risk-adjusted quality-improvement program for surgical patients. Patient stratification and risk adjustment are associated with Current Procedural Terminology codes and primary disease diagnosis is not considered. Our aim was to determine the association between disease diagnosis and SSI rates. METHODS: Data from all 2009 National Surgery Quality Improvement Program institutions were analyzed. ICD-9 codes were used to differentiate patients into cancer (colon or rectal), ulcerative colitis, regional enteritis, diverticular disease, and others. Diagnosis-specific SSI rates were compared with benign neoplasm, which had the lowest rate (8.9%). Logistic regression was performed adjusting for age, body mass index, American Society of Anesthesiologists classification, wound type, and relative value unit. RESULTS: There were 24,673 colorectal procedures, with 1,956 superficial incisional (SSSI), 398 deep incisional (DSSI), and 1,096 organ/space (O/SSSI) infections. Odds ratio (OR) and 95% confidence intervals compared with benign neoplasm diagnosis were computed after adjustment for each diagnosis category. In rectal cancer patients, significantly more SSSI (OR = 1.6; 95% CI, 1.3-2.1; p < 0.0001), DSSI (OR = 2.1; 95% CI, 1.3-3.7; p = 0.006), and O/SSSI (OR = 2.2; 95% CI, 1.6-3.0; p < 0.0001) developed. In diverticular patients, more SSSI (OR = 1.6; 95% CI, 1.3-2.0; p < 0.0001), but not DSSI or O/SSSI, developed. In ulcerative colitis patients, more DSSI (OR = 2.4; 95% CI, 1.2-4.9; p = 0.01), O/SSSI (OR = 2.1; 95% CI, 1.4-3.1; p = 0.0004), but fewer SSSIs, developed. CONCLUSIONS: We found that SSI type is associated with the underlying disease diagnosis. To facilitate colorectal SSI-reduction efforts, the disease process must be considered to design appropriate interventions. In addition, institutional comparisons based on aggregate or stratified SSI rates can be misleading if the colorectal disease mix is not considered. PMID- 22321526 TI - Outcomes and economic analysis of routine preoperative 4-dimensional CT for surgical intervention in de novo primary hyperparathyroidism: does clinical benefit justify the cost? AB - BACKGROUND: Preoperative imaging in patients with primary hyperparathyroidism provides important localization information. Although 4-dimensional neck CT (4DCT) can precisely localize hyperfunctioning parathyroid tissue, the contribution of 4DCT to overall cost, operating room time, and hospital stay is unknown. STUDY DESIGN: Records of 535 patients with primary hyperparathyroidism who underwent parathyroidectomy at our institution from 1996 to 2010 were reviewed. All patients had preoperative cervical ultrasonography and sestamibi scanning, and most (78.9%) underwent preoperative 4DCT. A decision tree was constructed to compare extent of procedure, operating room time, length of stay, failure rate, and total cost of each strategy (with and without 4DCT). Costs were determined by 2010 Medicare reimbursement. RESULTS: For patients with and without preoperative 4DCT, respectively, mean operating room time (64.4 vs 61.4 minutes; p = 0.58) and failure rate (1.9% vs 4.4%; p = 0.12) were not significantly different. Length of stay was higher in the no-CT cohort (0.61 vs 0.23 days; p < 0.001). Patients with a preoperative 4DCT were significantly more likely to undergo a limited parathyroidectomy (90.3% vs 80.5%; p = 0.004). Mean cost of care per patient in the CT and no-CT cohorts was $6,572 and $6,306, respectively. CONCLUSIONS: The introduction of routine 4DCT into the preoperative workup for surgical intervention in primary hyperparathyroidism does not appear to shorten operating room time or decrease failure rate significantly. However, preoperative 4DCT is associated with shorter hospital stays and improved rates of minimally invasive parathyroidectomy. This clinical benefit must be weighed against the increased cost associated with routine preoperative 4DCT. PMID- 22321527 TI - Does team-based primary health care improve patients' perception of outcomes? Evidence from the 2007-08 Canadian Survey of Experiences with Primary Health. AB - BACKGROUND: Team-based practice in primary care has been advocated for improved access, quality, effectiveness, and cost-efficiency of primary health care services, but there is limited empirical evidence supporting it. OBJECTIVE: To examine the impact of team-based practice on patients' perception of several process and outcome indicators from patients' perspective. DATA AND METHODS: Micro data from the 2007-08 Canadian Survey of Experiences with Primary Health Care conducted by Statistics Canada were utilized. Regression techniques and propensity score matching method were used to examine the impact of team-based primary care on several process and outcome indicators of primary care. RESULTS: The estimated average treatment effect of team-based care was positively significant and robust for access to after-hours care, quality of care, confidence in the system, overall coordination of care, and patient centeredness. Although the estimated average treatment effects for the two dimensions of follow up coordination, continuity of care, health promotion and disease prevention initiatives, and utilization of physician and nurse services were statistically significant, sensitivity test results showed that these results were unreliable. CONCLUSIONS: Team-based primary care improves patients' perception of process and outcome indicators in the area of access to after-hours care, quality of care, confidence in the system, overall coordination and patient centeredness. Future research needs to establish the causal link between team-based primary care and health outcomes of patients. PMID- 22321528 TI - The effect of hydroxypropyl-beta-cyclodextrin and sucrose on the sublingual absorption of midazolam in rabbits. AB - Sublingually administered midazolam is commonly used for premedication of pediatric patients. However, the irritating taste and low aqueous solubility of midazolam complicate its sublingual use. Cyclodextrin complexation can be used to improve both the taste and aqueous solubility of drugs, but based on earlier studies, the complexation efficiency of midazolam is relatively low. In the present study, the complexation of midazolam with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was investigated in the presence of various excipients. The aqueous solubility of midazolam improved significantly when HP-beta-CD was used together with sucrose. Sucrose alone did not increase the solubility of midazolam. In addition, sucrose increased the apparent stability constant of the midazolam/HP beta-CD complex. The pharmacokinetics of midazolam in different dosage forms was investigated in rabbits (dose 1mg/rabbit) after intravenous administration of midazolam solution and after sublingual administration of midazolam solution, midazolam/HP-beta-CD/sucrose solution or midazolam/HP-beta-CD/sucrose powder. Midazolam displayed rapid sublingual absorption (mean t(max) <=30min from the liquid formulations and 60 min from the solid formulation) with high absolute bioavailability (>68%) from all evaluated formulations. Based on the results, HP beta-CD and sucrose can be utilized together to prepare more concentrated and palatable midazolam formulations for sublingual administration in pediatric patients. PMID- 22321529 TI - The importance of information on relatives for the prediction of genomic breeding values and the implications for the makeup of reference data sets in livestock breeding schemes. AB - BACKGROUND: The theory of genomic selection is based on the prediction of the effects of genetic markers in linkage disequilibrium with quantitative trait loci. However, genomic selection also relies on relationships between individuals to accurately predict genetic value. This study aimed to examine the importance of information on relatives versus that of unrelated or more distantly related individuals on the estimation of genomic breeding values. METHODS: Simulated and real data were used to examine the effects of various degrees of relationship on the accuracy of genomic selection. Genomic Best Linear Unbiased Prediction (gBLUP) was compared to two pedigree based BLUP methods, one with a shallow one generation pedigree and the other with a deep ten generation pedigree. The accuracy of estimated breeding values for different groups of selection candidates that had varying degrees of relationships to a reference data set of 1750 animals was investigated. RESULTS: The gBLUP method predicted breeding values more accurately than BLUP. The most accurate breeding values were estimated using gBLUP for closely related animals. Similarly, the pedigree based BLUP methods were also accurate for closely related animals, however when the pedigree based BLUP methods were used to predict unrelated animals, the accuracy was close to zero. In contrast, gBLUP breeding values, for animals that had no pedigree relationship with animals in the reference data set, allowed substantial accuracy. CONCLUSIONS: An animal's relationship to the reference data set is an important factor for the accuracy of genomic predictions. Animals that share a close relationship to the reference data set had the highest accuracy from genomic predictions. However a baseline accuracy that is driven by the reference data set size and the overall population effective population size enables gBLUP to estimate a breeding value for unrelated animals within a population (breed), using information previously ignored by pedigree based BLUP methods. PMID- 22321530 TI - Figures and institutions of the neurological sciences in Paris from 1800 to 1950. Part II: Neurophysiology. AB - We present a short historical review of the major figures and institutions that contributed to make Paris a renowned centre of physiology and neurology during the xixth and the first half of the xxth century. We purposely chose to focus on the period 1800-1950, as 1800 corresponds to the actual beginning of experimental physiology of the nervous system - what is here referred to as "neuroscience"-and 1950 marks its exponential rise. Our presentation is divided into four chapters, matching the main disciplines which have progressed and contributed the most to the knowledge we have of the brain sciences: anatomy, physiology, neurology, and psychiatry-psychology. The present article is the second of four parts of this review which includes the chapter on neurophysiology with selected biographical sketches of Francois Magendie, Marie Jean-Pierre Flourens, Claude Bernard, Charles-Edouard Brown-Sequard, Etienne-Jules Marey, Alfred Fessard and Denise Albe-Fessard. PMID- 22321531 TI - Establishment of a transient transfection system and expression of firefly luciferase in Entamoeba invadens. AB - Entamoeba invadens is used as a model system to study trophozoite to cyst differentiation since Entamoeba histolytica, the causative agent of amoebiasis cannot encyst in culture. However, a system for introduction of cloned genes in E. invadens is not available. Here we report an electroporation-based method for transfection of E. invadens tophozoites and demonstrate the expression of firefly luciferase reporter gene driven from the E. invadens ribosomal protein L3 promoter. The efficiency of luciferase expression driven from the promoters of three different E. invadens genes (rpl3, rps10 and h2b) was tested and found to correlate with the in vivo expression levels of the respective gene. This system will permit the analysis of regulatory elements required for gene expression in E. invadens. PMID- 22321532 TI - Radiolabeled Zn-DPA as a potential infection imaging agent. AB - INTRODUCTION: A zinc-dipicolylamine analog (Zn-DPA) conjugated with a fluorophore (PSVue(r)794) has been shown to image bacterial infections in mice. However, radiolabeled Zn-DPA has not previously been considered for nuclear imaging of infection. METHODS: Both 111In-labeled DOTA-biotin and Zn-DPA-biotin were combined using streptavidin (SA) as a noncovalent linker. Mice injected intramuscularly with Streptococcus pyogenes (infection model) or with lipopolysaccharide (LPS) (inflammation model) were coinjected intravenously with 6 MUg of DPA as PSVue794 and as 111In-DOTA-biotin/SA/biotin-Zn-DPA. Periodic fluorescent and SPECT (single photon emission computed tomography)/CT (computed tomography) images were acquired, and biodistributions were obtained at 22 h. RESULTS: Histological examination confirmed the validity of both the infection and inflammation animal models. Both the whole-body optical and nuclear images showed obvious accumulations in the target thigh in both models at all time points. At 22 h, the average target thigh accumulation of 111In was 1.66%ID/g (S.D. 0.15) in the infection mice compared to 0.58%ID/g (S.D. 0.07) in the inflammation mice (P<.01), and the 111In target/normal thigh ratio was 2.8 fold higher in the infection animals compared to the inflammation animals. CONCLUSIONS: These preliminary results show that Zn-DPA within streptavidin targets S. pyogenes-infected mice similarly to its free fluorescent analogue. The significantly higher accumulation in the live bacterial infection thigh compared to that of the LPS-induced inflammation thigh suggests that Zn-DPA may be a promising imaging agent to distinguish between bacterial infections and sterile inflammations. PMID- 22321533 TI - Synthesis and evaluation of nucleoside radiotracers for imaging proliferation. AB - INTRODUCTION: Uncontrolled proliferation is a fundamental characteristic of cancer, and consequently, imaging of tumor proliferative status finds interest clinically both as a diagnostic tool and for evaluation of response to treatment. Positron emission tomography (PET) radiotracers based on a nucleoside core, such as 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT), have been extensively studied for this purpose. However, [18F]FLT suffers from poor DNA incorporation leading to occasional poor correlation of [18F]FLT tumor uptake with other proliferation indicators such as Ki-67 immunostaining. METHODS: N3-((1-(2-[18F]fluoroethyl)-1H [1,2,3]-triazol-4-yl)methyl)thymidine ([18F]2) and N3-((1-(2-[18F]fluoroethyl)-1H [1,2,3]-triazol-4-yl)methyl)-4'-thio-beta-thymidine ([18F]3) were synthesized by click chemistry from [18F]fluoroethyl azide and by direct nucleophilic substitution of a tosylate precursor. Metabolic stability and phosphorylation potential of the radiotracers were evaluated in vitro and compared to [18F]FLT. Further, metabolic stability and biodistribution analysis of [18F]2 and [18F]3 were evaluated in vivo. RESULTS: Stable isotope standards and radiochemistry precursors were synthesized by modification of existing literature procedures. [18F]2 and [18F]3 were synthesized in a radiochemical yield of 8%-12% (end of synthesis, non-decay corrected). Both nucleosides were stable to metabolic degradation by thymidine phosphorylase, and in vivo stability analysis showed only one metabolite for [18F]3. No phosphorylation of [18F]2 could be detected in HCT116 cell homogenates, and in the same assay, only minor (~8%) phosphorylation of [18F]3 was observed. Biodistribution in Balb/c mice indicated rapid clearance for [18F]2 and [18F]3 to a lesser extent. CONCLUSIONS: The favorable biodistribution and metabolic profile of [18F]3 warrant further investigation as a next-generation PET proliferation marker. PMID- 22321535 TI - Effects of mid-myocardial pacing on transmural dispersion of repolarization and arrhythmogenesis. AB - INTRODUCTION: Epicardial (Epi) activation of the left ventricular (LV) wall increases transmural dispersion of repolarization (TDR), which creates a substrate for the development of ventricular arrhythmia. We hypothesize that pacing from the LV mid-myocardium may decrease the TDR and occurrence of arrhythmias. METHODS AND RESULTS: A transmural electrocardiogram and transmembrane action potentials were simultaneously recorded from Epi, mid myocardial (M), and endocardial (Endo) layers of the arterially perfused canine LV wedge preparations (n= 8). Transmural dispersion of repolarization varied when the preparations were paced at each layer, respectively (Endo pacing, 35.6 +/- 6.6 ms; M pacing, 34.9 +/- 7.3 ms; Epi pacing, 72.4 +/- 4.9 ms; P< 0.001). A significant difference was noted in TDR between M pacing and Epi pacing (P< 0.001), but not between M pacing and Endo pacing (P= 0.831). This result was reproducible in the presence of ischaemia-reperfusion experiments (n= 8). Transmural dispersion of repolarization was amplified as compared with non ischaemic experiments and differed when preparations were paced at each layer (Endo pacing, 62.8 +/- 13.8 ms; M pacing, 63.3 +/- 13.3 ms; Epi pacing, 111.1 +/- 17.7 ms; P< 0.001). There was again no significant difference between Endo pacing and M pacing (P= 0.948). However, as pacing was shifted from M to Epi, there was a significant increase in TDR (P< 0.001). Ventricular arrhythmias were induced in two of eight ischaemic preparations during Epi pacing, but did not occur in either M or Endo pacing. CONCLUSION: Mid-myocardial pacing can significantly decrease the TDR and prevent the occurrence of ventricular arrhythmias as compared with Epi pacing. PMID- 22321536 TI - Projected burden of disease for Salmonella infection due to increased temperature in Australian temperate and subtropical regions. AB - OBJECTIVE: This study aimed to project the future disability burden of Salmonella infection associated with increased temperature in future in temperate and subtropical regions of Australia in order to provide recommendations for public health policy to respond to climate change. METHODS: Years Lost due to Disabilities (YLDs) were used as the measure of the burden of disease in this study. Regions in temperate and subtropical Australia were selected for this study. Future temperature change scenarios in the study were based on Australian projections, developed by the Commonwealth Scientific and Industrial Research Organization (CSIRO). YLDs for Salmonella infection in 2000 were calculated as the baseline data. YLDs for Salmonella infection in 2030 and 2050 under future temperature change scenarios were projected based on the quantitative relationship between temperature and disease examined in previously published regression models. Future demographic change was also considered in this analysis. RESULTS: Compared with the YLDs in 2000, increasing temperature and demographic changes may lead to a 9%-48% increase in the YLDs for Salmonella infection by 2030 and a 31%-87% increase by 2050 in the temperate region, and a 51%-100% increase by 2030 and an 87%-143% increase by 2050 in the subtropical region, if other factors remain constant. CONCLUSION: Temperature-related health burden of Salmonella infection in Australia may increase in the future due to change in climate and demography in the absence of effective public health interventions. Relevant public health strategies should be developed at an early stage to prevent and reduce the health burden of climate change. PMID- 22321537 TI - Tissue-specific accumulation of polybrominated diphenyl ethers (PBDEs) including Deca-BDE and hexabromocyclododecanes (HBCDs) in harbor seals from the northwest Atlantic. AB - Polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDs) are widely used flame retardants that enter coastal waters from multiple sources and biomagnify in marine food webs. PBDEs have been detected at relatively high concentrations in harbor seals, apex predators in the northwest Atlantic. Whereas tri- to hexa-BDEs readily biomagnified from prey fishes to seal blubber, Deca-BDE (BDE-209) did not biomagnify in blubber. To explore tissue-specific differences in the accumulation/biomagnification of BFRs, we analyzed tri- to Deca-BDES in liver of 56 harbor seals (6 adult males, 50 pups), and compared hepatic concentrations and biomagnification potential with those in blubber. HBCDs were analyzed in seal liver and blubber to enable similar comparisons. Hepatic SigmaPBDE (tri- to Octa-BDE) concentrations (range 35-19,547ng/glipid weight, lw) were similar to blubber concentrations, while alpha-HBCD levels in seal liver (range 2-279ng/glw) were significantly higher than levels in blubber. Tissue distribution of PBDEs and alpha-HBCD varied significantly by age and, surprisingly, by gender among the pups. Biomagnification of alpha-HBCD from fish to seal liver and blubber was negligible to low, implying that harbor seals can metabolize this persistent isomer. Similar to the patterns in blubber, tri- through hexa-BDEs were highly biomagnified from fish to seal liver. In contrast, BDE-209 concentrations in liver were up to five times higher than those in blubber, which is consistent with observations that BDE-209 migrates to perfused tissues such as the liver in biota. Although detection frequency was low, BDE-209 levels in seal liver were up to ten times higher than those in their prey fish, suggesting that the accumulation/biomagnification of Deca-BDE in marine food webs is tissue-specific. As BDE-209 is the dominant PBDE found in marine sediments, its biomagnification in marine ecosystems is of concern. PMID- 22321538 TI - Mercury risk from fluorescent lamps in China: current status and future perspective. AB - Energy-efficient lighting is one of the key measures for addressing electric power shortages and climate change mitigation, and fluorescent lamps are expected to dominate the lighting market in China over the next several years. This review presents an overview on the emissions and risk of mercury from fluorescent lamps during production and disposal, and discusses measures for reducing the mercury risk through solid waste management and source reduction. Fluorescent lamps produced in China used to contain relatively large amounts of mercury (up to 40 mg per lamp) due to the prevalence of liquid mercury dosing, which also released significant amounts of mercury to the environment. Upgrade of the mercury dosing technologies and manufacturing facilities had significantly reduced the mercury contents in fluorescent lamps, with most of them containing less than 10 or 5mg per lamp now. Occupational hygiene studies showed that mercury emissions occurred during fluorescent lamp production, particularly in the facilities using liquid mercury dosing, which polluted the environmental media at and surrounding the production sites and posed chronic health risk to the workers by causing neuropsychological and motor impairments. It is estimated that spent fluorescent lamps account for approximately 20% of mercury input in the MSW in China. Even though recycling of fluorescent lamps presents an important opportunity to capture the mercury they contain, it is difficult and not cost-effective at reducing the mercury risk under the broader context of mercury pollution control in China. In light of the significant mercury emissions associated with electricity generation in China, we propose that reduction of mercury emissions and risk associated with fluorescent lamps should be achieved primarily through lowering their mercury contents by the manufacturers while recycling programs should focus on elemental mercury-containing waste products instead of fluorescent lamps to recapture mercury from the waste stream cost-effectively. PMID- 22321540 TI - [Genotype analysis and personalized medicine]. PMID- 22321539 TI - Activation of the unfolded protein response by Listeria monocytogenes. AB - The endoplasmic reticulum (ER) responds to perturbation of homeostasis with stress. To maintain ER function, a signalling-circuitry has evolved which, when engaged, attempts to reduce a surplus of unfolded proteins by triggering the unfolded protein response (UPR). Several studies have implicated UPR in viral infections, neurodegenerative disorders and metabolic diseases but UPR has not yet been widely linked to bacterial infections. Here we demonstrate that the facultative intracellular pathogen Listeria monocytogenes (Lm) induces ER expansion and UPR prior to host cell entry. Lm activated protein kinase RNA-like ER kinase (PERK) evidenced by the phosphorylation of the alpha-subunit of eukaryotic translation initiation factor-2 (eIF2alpha), inositol-requiring protein-1 (IRE1) as shown by detection of spliced X-box binding protein-1 (XBP1) and activating transcription factor-6 (ATF6) as demonstrated by depletion of its inactive form. A mutant LmDeltahly strain that did not produce listeriolysin (LLO) lacked the UPR response. Conversely purified LLO activated UPR. Sustained infection with Lm resulted in apoptosis. Induction of ER stress by thapsigargin or tunicamycin reduced intracellular bacterial number. Our findings suggest that UPR plays an important role in the cell autonomous defence responses to bacterial infection. PMID- 22321541 TI - [Detection of epidermal growth factor receptor mutations in non-small-cell lung carcinoma by direct sequencing and correlations with clinicopathological characteristics and sample types]. AB - OBJECTIVE: To retrospectively analyze epidermal growth factor receptor (EGFR) gene mutation frequencies and distribution characteristics in Chinese patients with non-small-cell lung carcinoma (NSCLC) by direct gene sequencing. METHODS: Clinical samples from 443 NSCLC patients were obtained for EGFR gene mutation analysis, including 299 surgical specimens, 59 core biopsies and 85 fine needle aspiration and pleural effusion cytology specimens. All samples were processed from paraffin embedded blocks and microdissection was performed to enrich tumor cells. PCR based direct gene sequencing was used to investigate tyrosine kinase domain coding region involving exon 18 through 21. RESULTS: (1) Among 443 samples, 193 mutations were detected in 189 patients (42.7%) and 4 patients possessed two mutations involving two different exons in their tumor samples. The percentage of mutations involving exon 18 to 21 were 2.0% (4/193), 48.7% (94/193), 6.7% (13/193) and 42.5% (82/193) respectively. (2) There was no significant correlation of EGFR mutation with age, however, mutation rate (50.9%, 54/106) of exon 21 in patients over median age 57 was higher than that of the younger patients (32.2%, 28/87; P<0.01). (3) EGFR mutation rate was remarkably higher in female patients (53.5%, 107/200) than in male patients (33.7%, 82/243; P<0.01). (4) Mutation rate in adenocarcinomas (46.5%, 161/346) was much higher than in squamous cell carcinomas (13.3%, 4/30) and poorly differentiated carcinomas (24.1%, 7/29; P<0.01, P<0.05), while the adenosquamous carcinomas shared a mutation rate similar to that of adenocarcinoma (7/13, P>0.05). (5) In surgical samples, core biopsies and cytological samples, the EGFR mutation detection rates were 49.5% (148/299), 35.6% (21/59) and 23.5% (20/85) respectively. The fine needle aspiration and cytological samples showed much lower EGFR mutation detection rates (23.5%, 20/85) than that of surgical samples (49.5%, 148/299; P<0.01). CONCLUSIONS: (1) Direct gene sequencing is a reliable and effective method for the detection of EGFR mutations in NSCLC, particularly for unknown EGFR mutations. (2) EGFR mutations are more frequent in female patients and patients with adenocarcinoma NSCLC, involving mainly exon 19 and 21. (3) The mutation distribution in exons of EGFR gene appears age-related. (4) Detection rate of EGFR mutation varies in different sample types. Small biopsy and fine needle aspiration specimens are valuable materials for analyzing EGFR mutation in NSCLC, although rare false negativity may occur using such samples. PMID- 22321542 TI - [Epidermal growth factor receptor gene mutations and clinicopathologic correlation in 309 patients with non-small cell lung cancer]. AB - OBJECTIVE: To investigate the epidermal growth factor receptor (EGFR) gene mutation profile and related clinicopathological features in Chinese patients with non-small cell lung carcinoma (NSCLC). METHODS: Optimized oligonucleotide probe method was applied to detect EGFR mutations involving exons 18 - 21 using formalin fixed paraffin embedded tissue specimens of 309 NSCLC patients. The relationship between EGFR mutations and clinicopathological features were analyzed. RESULTS: The overall EGFR mutation rate was 34% (105/309) in this study cohort. Mutation rates in male and female were 30.4% (56/184) and 39.2% (49/125), respectively. The mutation rate was higher in patients less than 60 years of age, non-smokers and adenocarcinoma subtype than in their counterparts (P<0.05), with the percentage of 40.5% (87/215), 40.2% (51/127), 38.8% (78/201), respectively. The EGFR mutation types included exon 18 G719X mutation (5.7%, 6/105), exon 19 deletion (39.0%, 41/105) and exon 21 L858R mutation (55.2%, 58/105). In large cell undifferentiated carcinomas and squamous cell carcinomas, EGFR mutation rates were 22.2% (58/105) and 3/14, respectively. The overall mutation rate of exon 18 was low, but the proportion of its mutation was higher in squamous and adenosquamous carcinomas than in adenocarcinomas. CONCLUSIONS: There is a higher EGFR mutation rate in female, age of less than 60 years, non-smoker and adenocarcinoma among Chinese patients with NSCLC. Optimized oligonucleotide probe method is a sensitive and convenient method for the detection of EGFR mutations. PMID- 22321543 TI - [Relationship between mutations of epidermal growth factor receptor gene and clinicopathologic features of non-small cell lung cancers]. AB - OBJECTIVE: To explore the relationship between the mutations of epidermal growth factor receptor (EGFR) gene and clinicopathological characteristics in patients with non-small cell lung cancers (NSCLC). METHODS: Paraffin-embedded tissue specimens were obtained from 1444 patients with NSCLC. The genomic DNA was extracted. Mutations of EGFR gene (exons 19 and 21) were detected by real-time PCR. RESULTS: DNA was available in 1410 cases. Somatic mutations of the EGFR gene were identified in 401 cases (27.8%). Among patients with EGFR mutations, 41.4% (n=166) had del E746-A750 of exon19, 6.7% (n=27) had del L747-P753insS of exon 19, 50.3% (n=201) had L858R of exon 21, and 1.5% (n=6) had L861Q of exon 21. Woman, non-smoker and adenocarcinoma showed a higher percentage of EGFR mutation (43.2%, 37.6%, and 33.5%, respectively). However, there was no association among age, grades, lymph node metastasis, and TNM stages (P>0.05). The mutation rate of BAC subtype (61.3%, 19/31) and adenocarcinoma with BAC features (48.0%, 12/25) was significantly higher than that of conventional adenocarcinoma (32.4%, 336/1038). A further assess of the smoking status found a trend that the more increased smoking exposure, the lower the incidence of EGFR mutations. A multivariable analysis revealed that adenocarcinoma, never smoking, and female were independently associated with EGFR mutations (odds rations=3.381, 2.393, and 1.727, respectively). CONCLUSIONS: The detection rate of EGFR mutation is higher in Chinese patients, especially in non-smoking female patients with adenocarcinoma. Real-time PCR is a sensitive and accurate method to detect the mutations of EGFR gene and can therefore provide useful information for clinical treatment. PMID- 22321544 TI - [Detection of epidermal growth factor receptor gene mutations in non-small cell lung cancer using bi-loop probe specific primer quantitative PCR]. AB - OBJECTIVE: To investigate the sensitivity of bi-loop probe and specific primer quantitative PCR (BPSP-qPCR) in the detection of epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer (NSCLC). METHODS: BPSP-qPCR was employed to examine the presence of mutations of EFGR exon 19 through 21. Correlation of the mutations with clinicopathological characteristics and types of tumor samples were performed. RESULTS: In the cohort of 265 specimens, 30.2% (80/265) mutations were found to be 19-del and/or L858R. Females (39.7%, 31/78), non-smokers (41.0%, 43/105) and adenocarcinoma patients (37.8%, 51/135) had a higher mutation rate (P<0.05) among 184 patients whose profiles were available. T790M combined with 19-del and/or L858R accounted for 3.3% (6/184) of the mutations. Male metastatic tumors (29.6%, 8/27), pleural fluids of females (42.9%, 9/21) and non-smokers (40.7%, 11/27) were found to have higher percentage of 19-del and/or L858R mutations, in contrast, no mutations were found in the metastatic lesions of non-adenocarcinoma patients (P>0.05). CONCLUSIONS: BPSP qPCR is a robust method in detection of EGFR mutations with high consistency and sensitivity. The difference of EGFR mutations in primary tumors, metastatic lesions and pleural fluids suggests that EGFR tyrosine kinase inhibitors (EGFR TKI) treatment may have variable treatment effects depending on the tumor sites. PMID- 22321545 TI - [Detection of epidermal growth factor receptor gene mutations and its clinical significance in non-small cell lung cancers]. AB - OBJECTIVE: To investigate the detection technology and its clinical significance of the EGFR gene mutation in non-small cell lung cancer. METHODS: DNA direct sequencing methods by PCR amplification were used to detect EGFR gene exons 18-21 mutation and to analyze its clinical pathological significance in 192 patients with non-small cell lung cancer. RESULTS: 64 of the 192 cases presented with EGFR gene tyrosine kinase binding domain mutation (64/192, 33.3%), of which exon 19 deletion mutation rate was 60.9% (39/64), exon 21 alternative mutation rate was 39.1% (25/64), but exons 18 and 20 mutation was not found in this group of patients. EGFR gene mutation rate was 58.5%(24/41) in lung adenocarcinoma associated with bronchioloalveolar carcinoma differentiation, which was significantly higher than that of ordinary adenocarcinoma (37.9%, 33/87), squamous cell carcinoma (7.5%, 4/53), large cell carcinoma (1/5) and adenosquamous carcinoma (2/6, P<0.05). EGFR gene mutation rates in male patients (20.9%, 24/115), were significantly higher than in the females (51.9%, 40/77; P<0.01); non-smokers (50.0%, 57/114), significantly higher than that of smokers (9.0%, 7/78; P<0.01). CONCLUSIONS: DNA direct sequencing method by PCR amplification is stable and reliable in detection of EGFR gene mutation in non small cell lung cancer. It might provide a scientific basis for targeted therapy. PMID- 22321546 TI - [Epidermal growth factor receptor gene mutations, amplification and clinicopathologic correlation in patients with lung cancer]. AB - OBJECTIVE: To investigate the clinicopathological features of patients with lung cancers associated with epidermal growth factor receptor (EGFR) gene amplification and/or mutations. METHODS: Mutations and amplification status of EGFR gene were detected by PCR-DNA sequencing and FISH, respectively, followed by subsequent clinicopathological correlative studies. RESULTS: Among 454 patients, the overall mutation rate of EGFR was 48.2% (219/454). The EGFR mutation rate in females was significantly higher than that of males, 59.6% (118/198) vs. 39.5% (101/256), P<0.001. The mutation rate of EGFR gene of non-smokers was higher than that of smokers, 52.7% (147/279) vs. 41.4% (72/175), P=0.017. The mutation rate in patients with adenocarcinoma was higher than that in patients with other cancer types, 56.8% (193/340) vs. 22.8% (26/114), P<0.05. Moreover, a significant difference of mutation rates among different subtypes of adenocarcinomas was found (P=0.001). Among 134 patients with available FISH analysis, no statistical significance of EGFR gene amplification was found in age, gender, histopathological types and subtypes of adenocarcinomas (P>0.05). There was a significant correlation between EGFR mutation and its gene amplification (P=0.0005), although with poor consistency (P=0.275). CONCLUSIONS: EGFR gene mutations occur more frequently in females, non-smokers and patients with adenocarcinoma subtype. A significant variation of the mutation types exits among the subtypes of adenocarcinoma. The presence of EGFR amplification appears not related to age, gender, histopathological types of lung cancer and subtypes of adenocarcinoma. There is a significant correlation between EGFR mutations and its gene amplification (P=0.0005), although with poor consistency. PMID- 22321547 TI - [Relationship of epidermal growth factor receptor gene mutations, clinicopathologic features and prognosis in patients with non-small cell lung cancer]. AB - OBJECTIVE: To investigate epidermal growth factor receptor (EGFR) gene mutations in exons 19 and 21 of patients with non-small cell lung cancer (NSCLC) and to analyze the relationship of EGFR mutations with clinicopathological features and prognosis. METHODS: The EGFR gene exons 19 and 21 of paraffin-embedded tumor tissue were amplified by PCR, followed by direct sequencing in 282 surgically removed specimens of NSCLC. The relationship of EGFR gene mutations in NSCLC with clinicopathological features and prognosis were analyzed. RESULTS: EGFR mutations were detected in 120 of 282 (42.6%) patients with NSCLC. There were 61 cases of the mutations in exon 19 and 66 cases of the mutations in exon 21, including 7 cases of the mutations both in exons 19 and 21. Mutations were more frequently observed in women (55.2%, 53/96) than in men (36.0%, 67/186), in 51 to 60-years old (51.3%, 39/76) than <=50-years-old (30.4%, 21/69) and >60-years-old (43.8%, 60/137), in non-smokers (54.3%, 69/127) than smokers (32.9%, 51/155), there was negative correlation of EGFR mutations with smoking status (P=0.000, rs=-0.216). EGFR mutations were more frequently observed in adenocarcinomas (47.8%, 64/134), bronchiolo-alveolar carcinomas (73.0%, 27/37), adenosquamous carcinomas (7/9) than squamous cell carcinomas (23.6%, 17/72) and other types (16.7%, 5/30). The EGFR mutation rate in the well differentiated, the middle differentiated, the poorly differentiated and the undifferentiated was 55.7% (68/122), 50.8% (30/59), 22.7% (17/75), 19.2% (5/26) respectively, the incidences of EGFR mutations decreased with the degrading of differentiation, there was positive correlation of EGFR mutations with differentiation of lung cancer (P=0.000, rs=0.296). The patients with EGFR mutations had better prognosis than those with wild-type EGFR (P=0.027). There was no association of EGFR mutations with clinical TNM stage. CONCLUSIONS: EGFR mutations occur frequently in females, non-smokers and adenocarcinomas, bronchioloalveolar carcinomas, and adenosquamous carcinomas. The patients with EGFR mutations have better prognosis. The results may offer a practical approach to select the patients who may benefit from anti-EGFR target therapy. PMID- 22321548 TI - [Clinicopathologic features of calcifying fibrous tumor with reappraisal of its histogenesis]. AB - OBJECTIVE: To study the clinicopathologic features and histogenesis of calcifying fibrous tumor (CFT). METHODS: The clinical manifestations, histopathologic characteristics and immunophenotype were analyzed in 11 cases of CFT. RESULTS: The male-to-female ratio was 5:6, with a mean age of 38 years and age range of 25 to 52 years. The sites of involvement included abdominopelvic cavity (n=6), soft tissue (n=4) and scrotum (n=1). Most patients presented with a gradually enlarging and painless mass. Nearly half of the cases were associated with other diseases or history of inflammation, trauma or surgical intervention. One third of the tumors represented incidental findings and showed no recurrence after resection. Imaging revealed a solitary solid soft tissue mass or multiple nodules with clear borders and associated high-density calcifications. Macroscopically, the tumors were well-circumscribed but non-encapsulated. They ranged from 0.5 to 20.0 cm in diameter and were tan-greyish, round to oval, lobulated or irregular and solid with rubbery consistency. The cut surface was whitish to tan-yellowish, gritty and showed scattered spotty yellowish discoloration corresponding to the foci of dystrophic calcifications. Histologically, CFT was composed of hyalinized fibrous tissue and thickened vessel walls with interspersed bland spindly fibroblastic cells, scattered psammomatous calcifications, dystrophic calcification and lymphoplasmacytic infiltration. In addition, focal cloak-like polymorph infiltration at the tumor periphery and entrapment of adipocytes and nerves were demonstrated in some cases. Foci resembling solitary fibrous tumor, fibromatosis, keloid or inflammatory myofibroblastic tumor were observed. Immunohistochemical study showed that the tumor cells were diffusely positive for vimentin and focally positive for CD34, factor VIII-related antigen and beta catenin. The admixed plasma cells were notably IgG positive, with more than 50% being IgG4 positive. CONCLUSIONS: CFT has characteristic histopathologic manifestations and shows morphologic and immunohistochemical overlaps with known IgG4-related sclerosing diseases. It is possible that CFT may represent another example of IgG4-related diseases. It often runs a benign clinical course, with rare recurrence after surgical resection. Previous inflammation and trauma may be the precipitating factors of CFT. PMID- 22321549 TI - [Intravascular NK-cell lymphoma: a clinicopathologic study and literature review]. AB - OBJECTIVE: To study the clinicopathologic features and disease outcome of intravascular natural killer-cell lymphoma (IVNKL). METHODS: The histologic features, immunohistochemical findings and results of in-situ hybridization for Epstein-Barr virus-encoded RNA (EBER) were analyzed in 2 novel cases of IVNKL. Seven cases of IVNKL previously reported in the literature were reviewed. RESULTS: The patients were a 68-year-old woman and a 22-year-old man. They both presented with erythematous patches and nodules on their trunk and extremities. Skin biopsies confirmed the diagnosis of IVNKL. The tumor cells were positive for CD3, CD56, granzyme B and EBER. Both patients died 2 months after the diagnosis. Amongst the 9 reported cases, including those from the literature, the male was 4 cases, the female was 5 cases. The mean age of the patients was 45.7 years and the median age was 47 years. Skin lesions represented the commonest clinical manifestations. Multiple organ involvement was found in 7 cases and central nervous system was involved in 3 cases. Six patients died during 2 to 17 months of follow-up. The median survival was 9 months and the one-year survival rate was (35.6+/-18.6)%. The clinical outcome of the patients with multiple organ involvement was worse than that with skin manifestations only. The difference however was not statistically significant (P=0.083). CONCLUSIONS: IVNKL is a rare disease. Diagnosis should be made according to typical histologic findings, immunophenotype and EBER in-situ hybridization results. The overall prognosis of IVNKL is poor. Early diagnosis and treatment before multiorgan involvement may be helpful in improving the clinical outcome. PMID- 22321550 TI - [Immunohistochemistry of p57 and p53 protein in differential diagnosis of hydropic abortion, partial and complete hydatidiform mole]. AB - OBJECTIVE: To investigate the role of p57 and p53 immunohistochemistry in the differential diagnosis of hydropic abortion, partial hydatidiform mole and complete hydatidiform mole. METHODS: Immunohistochemical stains (EnVision method) for p57 and p53 were performed in tissue samples of normal placenta chorionic villi (n=10), abortion chorionic villi (n=12), partial hydatidiform (n=23) and complete hydatidiform moles (n=20). RESULTS: The expression of p57 was predominantly localized in the nuclei of villous cytotrophoblasts and stromal cells. The positive rates of p57 in normal placenta, hydropic abortion and partial hydatidiform mole were 10/10, 12/12, and 100% (23/23), respectively, with no significant difference among the groups (P>0.05). However, none of the complete hydatidiform moles analyzed exhibited p57 positivity in cytotrophoblasts and stromal cells. There was a significant difference between partial and complete hydatidiform moles (P<0.05). The expression of p53 was observed in the nuclei of cytotrophoblastic cells and intermediate trophoblasts. No p53 expression was seen in normal placenta and only 1 of 12 hydropic abortion showed p53 positivity. The positive rates of p53 expression in partial and complete hydatidiform mole were 60.9% (14/23) and 85.0% (17/20) respectively. It was significantly higher in partial hydatidiform mole than that in hydropic abortion. A significant difference was also found between partial and complete hydatidiform moles (P<0.05). CONCLUSIONS: Our findings confirm that p57 immunohistochemistry assists the differential diagnosis of complete hydatidiform mole from partial hydatidiform mole. Expression of p53 may be helpful in distinguishing partial hydatidiform mole from hydropic abortion. PMID- 22321551 TI - [Expression of Sox11 transcription factor in different types of B-cell lymphomas]. PMID- 22321552 TI - [Consensus for epidermal growth factor receptor gene mutation detection in non small cell lung cancer]. PMID- 22321553 TI - [Parotid gland carcinosarcoma: report of a case]. PMID- 22321554 TI - [Invasive micropapillary carcinoma of male breast with neuroendocrine differentiation: report of a case]. PMID- 22321555 TI - [Invasive ductal carcinoma and chronic lymphocytic leukemia: a unique case of collision tumor in breast]. PMID- 22321556 TI - [Primary endometrial stromal sarcoma arising in alimentary tract: a case report]. PMID- 22321557 TI - [Blastic plasmacytoid dendritic cell neoplasm: report of a case]. PMID- 22321558 TI - [Experience on epidermal growth factor receptor gene mutation analysis in non small cell lung cancer]. PMID- 22321559 TI - [Clinical applications of molecular biomarkers in urothelial carcinoma of bladder]. PMID- 22321560 TI - [Third-generation DNA sequencing: single molecule real-time DNA sequencing]. PMID- 22321561 TI - [Clinical practice guidelines for evaluation and treatment of osteoporosis associated to endocrine and nutritional conditions. Bone Metabolism Working Group of the Spanish Society of Endocrinology]. AB - OBJECTIVE: To provide practical recommendations for evaluation and treatment of osteoporosis associated to endocrine diseases and nutritional conditions. PARTICIPANTS: Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology, a methodologist, and a documentalist. METHODS: Recommendations were formulated according to the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed), using the following terms associated to the name of each condition: AND "osteoporosis", "fractures", "bone mineral density", and "treatment". Papers in English with publication date before 18 October 2011 were included. Current evidence for each disease was reviewed by two group members, and doubts related to the review process or development of recommendations were resolved by the methodologist. Finally, recommendations were discussed in a meeting of the Working Group. CONCLUSIONS: The document provides evidence-based practical recommendations for evaluation and management of endocrine and nutritional diseases associated to low bone mass or an increased risk of fracture. For each disease, the associated risk of low bone mass and fragility fractures is given, recommendations for bone mass assessment are provided, and treatment options that have shown to be effective for increasing bone mass and/or to decreasing fragility fractures are listed. PMID- 22321562 TI - Effects of co-habitation between Anopheles gambiae s.s. and Culex quinquefasciatus aquatic stages on life history traits. AB - BACKGROUND: The effective measures for the control of malaria and filariasis vectors can be achieved by targeting immature stages of anopheline and culicine mosquitoes in productive habitat. To design this strategy, the mechanisms (like biotic interactions with conspecifc and heterospecific larvae) regulating mosquito aquatic stages survivorship, development time and the size of emerging adults should be understood. This study explored the effect of co-habitation between An. gambiae s.s. and Cx. quinquefasciatus on different life history traits of both species under different densities and constant food supply in the habitats of the same size under semi-natural conditions. METHODS: Experiments were set up with three combinations; Cx. quinquefasciatus alone (single species treatment), An. gambiae s.s. alone (single species treatment); and An. gambiae s.s. with Cx. quiquefasciatus (co-habitation treatment) in different densities in semi field situation. RESULTS: The effect of co-habitation of An. gambiae s.s. and Cx. quinquefasciatus was found to principally affect three parameters. The wing-lengths (a proxy measure of body size) of An. gambiae s.s. in co-habitation treatments were significantly shorter in both females and males than in An. gambiae s.s single species treatments. In Cx. quinquefasciatus, no significant differences in wing-length were observed between the single species and co habitation treatments. Daily survival rates were not significantly different between co-habitation and single species treatments for both An. gambiae s.s. and Cx. quinquefasciatus. Developmental time was found to be significantly different with single species treatments developing better than co-habitation treatments. Sex ratio was found to be significantly different from the proportion of 0.5 among single and co-habitation treatments species at different densities. Single species treatments had more males than females emerging while in co-habitation treatments more females emerged than males. In this study, there was no significant competitive survival advantage in co-habitation. CONCLUSION: These results suggest that co-habitation of An. gambiae s.s. and Cx. quinquefasciatus in semi-natural conditions affect mostly An. gambiae s.s. body size. Hence, more has to be understood on the effects of co-habitation of An. gambiae s.s. and Cx. quinquefasciatus in a natural ecology and its possible consequences in malaria and filariasis epidemiology. PMID- 22321563 TI - Functional variability of the Lr34 durable resistance gene in transgenic wheat. AB - Breeding for durable disease resistance is challenging, yet essential to improve crops for sustainable agriculture. The wheat Lr34 gene is one of the few cloned, durable resistance genes in plants. It encodes an ATP binding cassette transporter and has been a source of resistance against biotrophic pathogens, such as leaf rust (Puccinina triticina), for over 100 years. As endogenous Lr34 confers quantitative resistance, we wanted to determine the effects of transgenic Lr34 with specific reference to how expression levels affect resistance. Transgenic Lr34 wheat lines were made in two different, susceptible genetic backgrounds. We found that the introduction of the Lr34 resistance allele was sufficient to provide comparable levels of leaf rust resistance as the endogenous Lr34 gene. As with the endogenous gene, we observed resistance in seedlings after cold treatment and in flag leaves of adult plants, as well as Lr34-associated leaf tip necrosis. The transgene-based Lr34 resistance did not involve a hypersensitive response, altered callose deposition or up-regulation of PR genes. Higher expression levels compared to endogenous Lr34 were observed in the transgenic lines both at seedling as well as adult stage and some improvement of resistance was seen in the flag leaf. Interestingly, in one genetic background the transgenic Lr34-based resistance resulted in improved seedling resistance without cold treatment. These data indicate that functional variability in Lr34 based resistance can be created using a transgenic approach. PMID- 22321564 TI - The expression of HSPs, anti-oxidants, and cytokines in plasma and bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome. AB - OBJECTIVES: We studied several acute inflammatory materials (AIM) such as various inflammatory cytokines, oxidative stress, and heat shock proteins in ARDS patients by simultaneously measuring from bronchoalveolar lavage fluid (BALF) and plasma. DESIGN AND METHODS: AIM were measured by using plasma and BALF sampling obtained from ARDS group (n=12) and non-ARDS group (n=12). RESULTS: In the BALF, only HSP 47 was significantly increased in ARDS group than non-ARDS group. In plasma, GRP 94, HSP 90, HSP 60, HSP 47, GPx-3, and IL-8 were increased significantly in ARDS group. In short, most of the AIM in BALF or plasma were not significantly different in ARDS group as compared with non-ARDS group. Ninety-day mortality was significantly related to HSP90, HSP 60 and GPx-3 in plasma but not in BALF. CONCLUSION: Alteration of AIM levels in both BALF or plasma of ARDS group was not remarkable compared with the non-ARDS group. Our result suggests the need to reconsider ARDS pathophysiology and therapeutic strategy. PMID- 22321565 TI - Analytical evaluation of the new Abbott Architect 25-OH vitamin D assay. AB - OBJECTIVES: Validation of the Architect 25-OH vitamin D assay. DESIGN AND METHODS: Determination of repeatability, reproducibility, accuracy profile and 25(OH)-vitamin D2 recovery on native samples. Comparison with DiaSorin Liaison and RIA. RESULTS AND CONCLUSION: Coefficients of variation: <6% (13.6 ng/mL) and 2.2% (78.1 ng/mL). Functional sensitivity: 5 ng/mL. Accuracy profile shows that the method is validated between 13.6 and 78.1 ng/mL. Recovery of 25(OH)D2: 75,8%( 95% CI: 61.9-89.7%). Good correlation with DiaSorin RIA and Liaison <50 ng/mL; above this threshold a systematic positive bias was observed. PMID- 22321566 TI - The emergence and current performance of a health research system: lessons from Guinea Bissau. AB - BACKGROUND: Little is known about how health research systems (HRS) in low-income countries emerge and evolve over time, and how this process relates to their performance. Understanding how HRSs emerge is important for the development of well functioning National Health Research Systems (NHRS). The aim of this study was to assess how the HRS in Guinea Bissau has emerged and evolved over time and how the present system functions. METHODS: We used a qualitative case-study methodology to explore the emergence and current performance of the HRS, using the NHRS framework. We reviewed documents and carried out 39 in-depth interviews, ranging from health research to policy and practice stakeholders. Using an iterative approach, we undertook a thematic analysis of the data. RESULTS: The research practices in Guinea Bissau led to the emergence of a HRS with both local and international links and strong dependencies on international partners and donors. The post-colonial, volatile and resource-dependent context, changes in donor policies, training of local researchers and nature of the research findings influenced how the HRS evolved. Research priorities have mostly been set by 'expatriate' researchers and focused on understanding and reducing child mortality. Research funding is almost exclusively provided by foreign donors and international agencies. The training of Guinean researchers started in the mid nineties and has since reinforced the links with the health system, broadened the research agenda and enhanced local use of research. While some studies have made an important contribution to global health, the use of research within Guinea Bissau has been constrained by the weak and donor dependent health system, volatile government, top-down policies of international agencies, and the controversial nature of some of the research findings. CONCLUSIONS: In Guinea Bissau a de facto 'system' of research has emerged through research practices and co-evolving national and international research and development dynamics. If the aim of research is to contribute to local decision making, it is essential to modulate the emerged system by setting national research priorities, aligning funding, building national research capacity and linking research to decision making processes. Donors and international agencies can contribute to this process by coordinating their efforts and aligning to national priorities. PMID- 22321567 TI - Identifying specific interpretations and use of safety behaviours in people with distressing visual hallucinations: an exploratory study. AB - BACKGROUND: Visual hallucinations (VH) are a common experience and can be distressing and disabling, particularly for people suffering from psychotic illness. However, not everyone with visual hallucinations reports the experience to be distressing. Models of VH propose that appraisals of VH as a threat to wellbeing and the use of safety seeking behaviours help maintain the distress. AIMS: This study investigated whether people with distressing VH report threat appraisals and use safety behaviours. METHOD: The study utilized a single group descriptive design, in which 15 participants with psychosis and VH were asked questions in order to assess the content, distress, appraisals, and behaviours associated with visual hallucinations. RESULTS: People who found visual hallucinations distressing (n = 13) held negative appraisals about those hallucinations and specifically saw them as a threat to their physical or psychological wellbeing. They also engaged in safety seeking behaviours that were logically related to the appraisal and served to maintain the distress. CONCLUSIONS: People with distressing VH regard them as a threat to their wellbeing and use safety seeking behaviours as a result of this perceived threat. These key processes are potential targets for treatments that will alleviate the distress associated with VH. PMID- 22321568 TI - Antibiotics as immunomodulant agents in COPD. AB - It is widely accepted that some antibiotics have activities beyond their direct antibacterial effects. Macrolide is the antibiotic class with more convincing studies and evidence on its immunomodulatory and anti-inflammatory activities. Different clinical studies have shown that macrolide prophylaxis in patients with moderate-severe chronic obstructive pulmonary disease (COPD) can have a significant impact on the exacerbation rate reducing morbidity and, potentially, mortality of the disease. Other antibiotics, such as fluoroquinolones, demonstrate a variety of immunomodulatory effects but only few clinical data are available in COPD. New macrolide derivatives devoid of antibacterial activity have been synthetized. This review analyses the relevance of immunomodulatory and anti-inflammatory effects of antibiotics in the management of COPD. PMID- 22321569 TI - Pathophysiology of saphenous vein graft failure: a brief overview of interventions. AB - Coronary artery bypass graft surgery (CABG) is widely used for the treatment of atheromatous stenosis of coronary arteries. However, as many as 50% of grafts fail within 10 years after CABG due to neointima (NI) formation, a process involving the proliferation of vascular smooth muscle cells (VSMCs) and superimposed atherogenesis. To date no therapeutic intervention has proved successful in treating late vein graft failure. However, several diverse approaches aimed at preventing neointimal formation have been devised which have yielded promising results. In this review, therefore, we will summarise the pathophysiology of vein graft disease and then briefly consider interventional approaches to prevent late vein graft failure which include surgical technique, conventional pharmacology, external sheaths, cytostatic drugs and gene transfer. PMID- 22321570 TI - Therapeutic potential of marine n-3 fatty acids in CABG patients. AB - Dietary intake of marine n-3 polyunsaturated fatty acids (PUFA) has beneficial effects in various cardiac disorders. Few studies have, however, investigated the therapeutic potential of n-3 PUFA in patients undergoing coronary artery bypass grafting (CABG). Five heterogeneous randomized studies on n-3 PUFA for prevention of postoperative atrial fibrillation have yielded conflicting results. Increased venous graft patency rates following CABG were seen in another study in patients treated with n-3 PUFA. Finally, supplements with n-3 PUFA postoperatively have been associated with a lower risk of repeat revascularization and lower mortality in patients with poor ventricular function. Data are still few, and more studies are needed to clarify the therapeutic potential of n-3 PUFA in patients undergoing CABG. PMID- 22321571 TI - Molecular characterization of DSC1 orthologs in invertebrate species. AB - DSC1 and BSC1 are two founding members of a novel family of invertebrate voltage gated cation channels with close structural and evolutionary relationships to voltage-gated sodium and calcium channels. In this study, we searched the published genome sequences for DSC1 orthologs. DSC1 orthologs were found in all 48 insect species, and in other invertebrate species belonging to phyla Mollusca, Cnidaria, Hemichordata and Echinodermata. However, DSC1 orthologs were not found in four arachnid species, Ixodes scapularis, Rhipicephalus microplus, Tetranychus urticae and Varroa destructor, two species in Annelida or any vertebrate species. We then cloned and sequenced NlSC1 and BmSC1 full-length cDNAs from the brown planthopper (Nilaparvata lugens) and the silkworm (Bombyx mori), respectively. NlSC1 and BmSC1 share about 50% identity with DSC1, and the expression of NlSC1 and BmSC1 transcripts was most abundant in the head and antenna in adults. All DSC1 orthologs contain a unique and conserved DEEA motif, instead of the EEEE or EEDD motif in classical calcium channels or the DEKA motif in sodium channels. Phylogenetic analyses revealed that DSC1 and its orthologs form a separate group distinct from the classical voltage-gated sodium and calcium channels and constitute a unique family of cation channels. The DSC1/BSC1-family channels could be potential targets of new and safe insecticides for pest control. PMID- 22321572 TI - Triallelic SNP-mediated genotyping of regenerated protoplasts of the heterokaryotic fungus Rhizoctonia solani. AB - The aneuploid and heterokaryotic nuclear condition of the soil fungus Rhizoctonia solani have provided challenges in obtaining a complete genome sequence. To better aid in the assembly and annotation process, a protoplast and single nucleotide polymorphism (SNP)-based method was developed to identify regenerated protoplasts with a reduced nuclear genome. Protocol optimization experiments showed that enzymatic digestion of mycelium from a 24 h culture of R. solani increased the proportion of protoplasts with a diameter of <=7.5 MUm and 1-4 nuclei. To determine whether strains regenerated from protoplasts with a reduced number of nuclei were genetically different from the parental strain, triallelic SNPs identified from variance records of the genomic DNA sequence reads of R. solani were used in PCR-based genotyping assays. Results from 16 of the 24 SNP based PCR assays provided evidence that one of the three alleles was missing in the 11 regenerated protoplast strains, suggesting that these strains represent a reduced genomic complement of the parental strain. The protoplast and triallelic SNP-based method used in this study may be useful in strain development and analysis of other basidiomycete fungi with complex nuclear genomes. PMID- 22321573 TI - Responses of Pseudomonas putida to toxic aromatic carbon sources. AB - A number of bacteria can use toxic compounds as carbon sources and have developed complex regulatory networks to protect themselves from the toxic effects of these compounds as well as to benefit from their nutritious properties. As a model system we have studied the responses of Pseudomonas putida strains to toluene. Although this compound is highly toxic, several strains are able to use it for growth. Particular emphasis was given to the responses in the context of taxis, resistance and toluene catabolism. P. putida strains analysed showed chemotactic movements towards toluene. Strain DOT-T1E was characterised by an extreme form of chemotaxis, termed hyperchemotaxis, which is mediated by the McpT chemoreceptor encoded by plasmid pGRT1. Close McpT homologs are found in a number of other plasmids encoding degradation pathways of toxic compounds. The pGRT1 plasmid harbours also the genes for the TtgGHI efflux pump which was identified as the primary determinant for the resistance of strain DOT-T1E towards toluene. Pump expression is controlled by the TtgV repressor in response to a wide range of different mono- and biaromatic compounds. Strain DOT-T1E is able to degrade toluene, benzene and ethylbenzene via the toluene dioxygenase (TOD) pathway. The expression of the pathway operon is controlled by the TodS/T two component system. The sensor kinase TodS recognizes toluene with nanomolar affinity, which in turn triggers an increase in its autophosphorylation and consequently transcriptional activation. Data suggest that transcriptional activation of the TOD pathway occurs at very low toluene concentrations whereas TtgV mediated induction of pump expression sets in as the toluene concentration further increases. PMID- 22321574 TI - Targeting Gene-Viro-Therapy with AFP driving Apoptin gene shows potent antitumor effect in hepatocarcinoma. AB - BACKGROUND: Gene therapy and viral therapy are used for cancer therapy for many years, but the results are less than satisfactory. Our aim was to construct a new recombinant adenovirus which is more efficient to kill hepatocarcinoma cells but more safe to normal cells. METHODS: By using the Cancer Targeting Gene-Viro Therapy strategy, Apoptin, a promising cancer therapeutic gene was inserted into the double-regulated oncolytic adenovirus AD55 in which E1A gene was driven by alpha fetoprotein promoter along with a 55 kDa deletion in E1B gene to form AD55 Apoptin. The anti-tumor effects and safety were examined by western blotting, virus yield assay, real time polymerase chain reaction, 3-(4,5-dimethylthiazol-2 yl)-2, 5-diphenyltetrazolium bromide assay, Hoechst33342 staining, Fluorescence activated cell sorting, xenograft tumor model, Immunohistochemical assay, liver function analysis and Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling assay. RESULTS: The recombinant virus AD55-Apoptin has more significant antitumor effect for hepatocelluar carcinoma cell lines (in vitro) than that of AD55 and even ONYX-015 but no or little impair on normal cell lines. Furthermore, it also shows an obvious in vivo antitumor effect on the Huh-7 liver carcinoma xenograft in nude mice with bigger beginning tumor volume till about 425 mm3 but has no any damage on the function of liver. The induction of apoptosis is involved in AD55-Apoptin induced antitumor effects. CONCLUSION: The AD55-Apoptin can be a potential anti-hepatoma agent with remarkable antitumor efficacy as well as higher safety in cancer targeting gene-viro-therapy system. PMID- 22321575 TI - Prevalence of antibodies against three species of Leishmania (L. mexicana, L. braziliensis, L. infantum) and possible associated factors in dogs from Merida, Yucatan, Mexico. AB - Leishmania spp. has been recorded in humans and in dogs, and numerous studies have demonstrated that dogs act as reservoirs for visceral leishmaniasis. The objective of this study was to determine the prevalence of three species of the Leishmania genus and possible associated factors in sera of 218 dogs from two different populations in Merida, Yucatan (Mexico). The sera were analyzed to detect antibodies against L. mexicana, L. braziliensis, and L. infantum using the superoxide dismutase- enzyme-linked immunosorbent assay (SOD-ELISA) and Western blot as confirmation. The Fe-SOD excreted was used as the antigenic fraction for the three Leishmania species. The prevalence values found were 30.2% (L. mexicana), 8.2% (L. braziliensis), and 11.9% (L. infantum), with L. mexicana seroprevalence being greater than L. braziliensis and L. infantum (p<0.05). Five percent (11/218) of the dogs showed antibodies against L. mexicana/L. braziliensis, 5.5% (12/218) with L. mexicana/L. infantum and 1.8% (4/218) with L. mexicana/L. braziliensis/L. infantum. No relationship (p>0.05) was found between antibodies against L. mexicana and breed, age, physical condition, or cutaneous lesions in dogs. This study provides evidence of antibodies against L. mexicana, L. braziliensis and L. infantum in dog populations from Merida, Mexico. PMID- 22321579 TI - The relationship between anxiety sensitivity and obsessive-compulsive symptom dimensions. AB - BACKGROUND AND OBJECTIVES: Anxiety sensitivity (AS), the tendency to fear arousal related body sensations based on beliefs that they are dangerous, is a cognitive vulnerability factor for certain anxiety symptoms such as panic and posttraumatic stress symptoms. Very little research, however, has examined the relationship between AS and obsessive-compulsive (OC) symptoms, which was the objective of the current research. METHODS: We administered dimensional measures of AS and OC symptoms to a large sample of undergraduate students (N = 636). We also included measures of general distress and cognitive distortions related to OCD (i.e., obsessive beliefs) as control variables. RESULTS: Regression analyses indicated that AS was predictive of OC symptoms even after controlling for general distress and obsessive beliefs. In addition, the three domains of AS (physical, social, and cognitive concerns) were differentially associated with the four dimensions of OC symptoms (contamination, responsibility for harm, symmetry, and unacceptable thoughts). LIMITATIONS: Our findings are based on a non-clinical student sample and their generalization to OCD requires replication with a sample of OCD patients. CONCLUSIONS: These results provide preliminary evidence that AS plays a role in OC symptoms. Implications for clinical practice and for future research are discussed. PMID- 22321580 TI - Engineering starch accumulation by manipulation of phosphate metabolism of starch. AB - A new understanding of leaf starch degradation has emerged in the last 10 years. It has been shown that starch phosphorylation and dephosphorylation are critical components of this process. Glucan, water dikinase (GWD) (and phosphoglucan, water dikinase) adds phosphate to starch, and phosphoglucan phosphatase (SEX4) removes these phosphates. To explore the use of this metabolism to manipulate starch accumulation, Arabidopsis (Arabidopsis thaliana) plants were engineered by introducing RNAi constructs designed to reduce expression of AtGWD and AtSEX4. The timing of starch build-up was altered with ethanol-inducible and senescence induced gene promoters. Ethanol induction of RNAi lines reduced transcript for AtGWD and AtSEX4 by 50%. The transgenic lines had seven times more starch than wild type at the end of the dark period but similar growth rates and total biomass. Elevated leaf starch content in maize leaves was engineered by making an RNAi construct against a gene in maize that appeared to be homologous to AtGWD. The RNAi construct was expressed using the constitutive ubiquitin promoter. Leaf starch content at the end of a night period in engineered maize plants was 20 fold higher than in untransformed plants with no impact on total plant biomass. We conclude that plants can be engineered to accumulate starch in the leaves with little impact on vegetative biomass. PMID- 22321581 TI - Using reminder/recall systems to improve influenza immunization rates in children with asthma. AB - INTRODUCTION: Asthma is a major public health concern in the U.S. pediatric population. Children with asthma tend to fare worse when they acquire respiratory illnesses such as influenza, requiring more episodic office visits and hospitalizations than do healthy children with the same illnesses. Despite the American Academy of Pediatrics recommendation that children with chronic diseases be immunized for seasonal influenza annually, influenza immunization rates in this population peaks at < 30%. The purpose of this literature review was to examine the effectiveness of reminder/recall systems in improving influenza immunization rates among children with asthma. METHOD: This literature review was conducted using PubMed, CINAHL, EMBASE, and Cochrane. Of the 178 articles found, 12 met criteria for inclusion. Articles were included if they addressed influenza vaccination in asthmatic children and "high-risk" children and considered asthmatics in the definition of "high risk." Additionally, inclusion criteria required discussion of at least one mode of reminder method or recall method that was used to influence the rate of influenza vaccination in children with asthma. For the purposes of this review, "reminders" is defined as any action performed by health provider or representative of the health provider that was aimed at informing and/or reiterating to patients the importance of influenza vaccination for asthmatic children and/or the potential for increased morbidity with acquisition of the flu and/or availability of the vaccine. "Recall" methods included all efforts made by the health provider or his/her representative to encourage patients to return to clinics for vaccination during the influenza season. Articles were excluded if they focused on improving influenza vaccination rates in healthy children and if they used reminder/recall systems to influence vaccination against diseases other than influenza. No systematic review was found on this particular topic. RESULTS: Providers have used reminder and recall systems that alert patients of the need for vaccination and encourage compliance with this recommendation. Implemented techniques included verbal and mailed reminders, electronically generated alerts, and year-round scheduling of flu vaccination appointments. DISCUSSION: Improvements have been seen in influenza immunization rates with the implementation of reminder/recall systems; however, most have been modest. Enhancements in patient education and access to vaccination are other areas of needed improvement. PMID- 22321582 TI - [Studies on prevention and control of infectious diseases: opportunities and challenges]. PMID- 22321583 TI - [Reducing maternal mortality and achieving the Millennium Development Goal]. PMID- 22321584 TI - [Factors of drug resistant bacteria emergence and dissemination]. PMID- 22321585 TI - [The warning model and influence of climatic changes on hemorrhagic fever with renal syndrome in Changsha city]. AB - OBJECTIVE: To realize the influence of climatic changes on the transmission of hemorrhagic fever with renal syndrome (HFRS), and to explore the adoption of climatic factors in warning HFRS. METHODS: A total of 2171 cases of HFRS and the synchronous climatic data in Changsha from 2000 to 2009 were collected to a climate-based forecasting model for HFRS transmission. The Cochran-Armitage trend test was employed to explore the variation trend of the annual incidence of HFRS. Cross-correlations analysis was then adopted to assess the time-lag period between the climatic factors, including monthly average temperature, relative humidity, rainfall and Multivariate Elno-Southern Oscillation Index (MEI) and the monthly HFRS cases. Finally the time-series Poisson regression model was constructed to analyze the influence of different climatic factors on the HFRS transmission. RESULTS: The annual incidence of HFRS in Changsha between 2000 - 2009 was 13.09/100 000 (755 cases), 9.92/100 000 (578 cases), 5.02/100 000 (294 cases), 2.55/100 000 (150 cases), 1.13/100 000 (67 cases), 1.16/100 000 (70 cases), 0.95/100 000 (58 cases), 1.40/100 000 (87 cases), 0.75/100 000 (47 cases) and 1.02/100 000 (65 cases), respectively. The incidence showed a decline during these years (Z = -5.78, P < 0.01). The results of Poisson regression model indicated that the monthly average temperature (18.00 degrees C, r = 0.26, P < 0.01, 1-month lag period; IRR = 1.02, 95%CI: 1.00 - 1.03, P < 0.01), relative humidity (75.50%, r = 0.62, P < 0.01, 3-month lag period; IRR = 1.03, 95%CI: 1.02 - 1.04, P < 0.01), rainfall (112.40 mm, r = 0.25, P < 0.01, 6-month lag period; IRR = 1.01, 95CI: 1.01 - 1.02, P = 0.02), and MEI (r = 0.31, P < 0.01, 3-month lag period; IRR = 0.77, 95CI: 0.67 - 0.88, P < 0.01) were closely associated with monthly HFRS cases (18.10 cases). CONCLUSION: Climate factors significantly influence the incidence of HFRS. If the influence of variable-autocorrelation, seasonality, and long-term trend were controlled, the accuracy of forecasting by the time-series Poisson regression model in Changsha would be comparatively high, and we could forecast the incidence of HFRS in advance. PMID- 22321586 TI - [Characteristics of Yersinia enterocolitica genes isolated in Ningxia Hui autonomous region from 1997 to 2010]. AB - OBJECTIVE: To investigate the distribution of virulent genes of Yersinia enterocolitica (Y. enterocolitica) in Ningxia Hui autonomous region and the characteristics of the molecular patterns of Y. enterocolitica. METHODS: 283 strains of Y. enterocolitica were isolated in Ningxia Hui autonomous region between year 1997 and 2010. The genes ail, ystA, ystB, yadA and virF were analyzed by PCR method; the chromosomal DNA of Y. enterocolitica was digested by restriction endonucleases NotI and processed by pulsed-field gel electrophoreses (PFGE); and then the cluster analysis were conducted by BioNumeric computer software towards the above results. RESULTS: Of all, 209 strains of serotypes O:3 and O:9 Y.enterocolitica showed positive virulence of genes ail, ystA, yadA and virF; 97.6% (204/209) of which, the ystB virulence were negative. The virulence of all genes in serotype O:8 and serum-unclassified strains were negative. 9 out of 11 strains of serotype O:5 Y. enterocolitica showed negative virulence of the above five genes. By PFGE, according to the NotI Macrorestriction Map on chromosomal DNA, the 29 strains of serotype O:3 Y. enterocolitica were divided into 12 PFGE patterns, 2 of which were dominant patterns which could be found in over 5 strains; and the 180 strains of serotype O:9 Y. enterocolitica were divided into 13 patterns, 4 of which were dominant patterns which existed in over 10 strains; which were isolated individually from pigs and house mouse, pigs and dogs as well as pigs and wild rabbits. CONCLUSION: Y.enterocolitica serotypes O:3 and O:9 were pathogenic in Ningxia, and serotype O:3 becomes predominant gradually. O:5, O:8 and serum-unclassified serotypes were non-pathogenic. PMID- 22321587 TI - [Sequence-based typing of 82 strains of serotype I Legionella pneumophila isolated from 9 provinces in China]. AB - OBJECTIVE: To analyze the characteristics of Sequence-based Typing (SBT) of the Serotype 1 Legionella pneumophila (Lp1) isolated from environmental water in China, and then create a preliminary database. METHODS: A total of 82 strains of Lp1 isolated from environmental water in 9 provinces of China between 2005 and 2008 were genotyped by SBT method and Pulsed-field Gel Electrophoresis (PFGE) method. The results of the two different typing methods were then compared by cluster analysis, adopting BioNumerics version 5.1 software. RESULTS: By SBT method, the 82 strains of Lp1 were divided into 22 ST types, of which 17 new types and one new allele was discovered. The dominant type was ST-1 type, found in 8 provinces, accounting for 46.3% (38/82). ST-1, ST-150, ST-154, ST-159, ST 160 and ST-630 types were found in more than 2 isolated-sites; while more than 2 different ST types were found in 5 isolated-sites, as site B4, B5, B6, S3 and S8. In cluster analysis, 15 ST types were grouped into three complexes (ST-1 complex, ST-154 complex and ST-149 complex); and the other 7 ST types were not assigned complex. By PFGE method, 46 banding patterns were observed. As a result of the combination of the two methods, the 82 isolates strains could be divided into 54 molecular types, which showed a reliable accordance in the cluster analysis between the two methods. CONCLUSION: The SBT of the Lp1 in environmental water in China was unique. From the study, a preliminary SBT database was set up. PMID- 22321588 TI - [Molecular characteristics and antibiotic resistances of Vibrio cholerae O1 isolates in Hangzhou in 2009]. AB - OBJECTIVE: To study the molecular characteristics and antibiotic resistances of Vibrio cholerae (V. cholerae) O1 isolates in Hangzhou in 2009. METHODS: The virulence genes ctxA and tcpA of the thirty V. cholerae O1 isolates from 7 counties and districts of Hangzhou were detected by PCR. Pulsed-field gel electrophoresis (PFGE) was performed for molecular typing and similarity analysis. Antibiotic resistances of these isolates were measured by the Kirby Bauer method. RESULTS: Virulence gene analysis showed that 80.00% (24/30) of the genotype in V. cholerae isolates was ctxA- and tcpA+, 13.33% (4/30) was ctxA- and tcpA-, and 6.67% (2/30) was ctxA+ and tcpA+. Twenty-seven isolates tested were typed into 11 PFGE patterns (P1-P11). Twenty-three isolates with genotype ctxA- and tcpA+ were clustered into 7 PFGE patterns (P1-P7, termed P1-like cluster) with the similarity to be equal or greater than 91.4%, and 56.52%(13/23) of them belong to P1. 7 isolates with very high similarity (97.6%), belonging to P1 (6 isolates), and P2 (1 isolate), respectively, were collected from one foodborne disease outbreak. The resistant rates of the 24 isolates with genotype ctxA- and tcpA+ to ampicillin, tobramycin and amikacin were 20.83% (5/24), 4.17% (1/24) and 4.17% (1/24), respectively. CONCLUSION: The genotype of the epidemic strains of V. cholerae O1 isolates in Hangzhou in 2009 with high similarity was ctxA- and tcpA+; The level of drug resistances of this kind of V. cholerae O1 isolates were not high. PMID- 22321589 TI - [Characteristics of Salmonella enterica serovar Senftenberg lacking Salmonella pathogenicity island 1]. AB - OBJECTIVE: To study the characteristics of the strains of Salmonella enterica (S. enterica) serovar Senftenberg lacking Salmonella pathogenicity island 1 (SPI-1). METHODS: A total of 10 strains of S. enterica serovar Senftenberg were isolated from 10 cases of diarrhea patients. Pulsed field gel electrophoresis (PFGE), PCR, sequencing techniques and cell invasion test were adapted to study the molecular types and invasiveness of the genes and cells; and made a comparison between the 10 strains and the strains (C02013) isolated in Shenzhen in 2002. RESULTS: The 10 Senftenberg isolated (S09007-S09012, S09014-S09017) in Shanghai showed three PFGE patterns, which were significantly different from the strains isolated in Shenzhen. PCR-amplified results indicated the invasion gene (invA), secreted effector protein gene (sipA) and gene fragments as fhlA-hilA, hilA-spaP and spaP invH in the 10 strains of SPI-1 were all negative. The sequencing results revealed that the 10 strains isolated in Shanghai lacked most parts of SPI-1 genes, as fragments from orgA to invH and parts of orgA gene itself; however, compared with strains isolated in Shenzhen, the sprB-orgC gene existed. The missing parts of genes were replaced by a simple insertion sequence (IS) of 1000 bp in the strains isolated both in Shenzhen in 2002 and in Shanghai in 2006. The invasiveness rates of the 10 strains (S09007-S09012, S09014-S09017) towards Hela cells were (0.0053 +/- 0.0024)%, (0.0046 +/- 0.0006)%, (0.0047 +/- 0.0003)%, (0.0064 +/- 0.0012)%, (0.0065 +/- 0.0011)%, (0.0070 +/- 0.0020)%, (0.0115 +/- 0.0030)%, (0.0099 +/- 0.0039)%, (0.0180 +/- 0.0135)% and (0.0031 +/- 0.0012)%, respectively; which were all significantly lower than the rate of invA-positive control strain STM1344 ((5.0800 +/- 0.6333)%); lower or close to the rate of invA lacked artificial-mutated strain STMinvA-((0.0193 +/- 0.0045)%). CONCLUSION: SPI 1 genes are not essential for the diarrhea caused by S. enterica serovar Senftenberg. PMID- 22321590 TI - [Risk factors of death cases of hand-foot-and-mouth disease in Hunan province]. AB - OBJECTIVE: To study risk factors of death cases of hand foot and mouth diseases (HFMD) in Hunan province, so as to provide scientific evidence for further prevention and control. METHODS: The 105 death cases of HFMD between January and October, 2010 in Hunan Province were selected as case group; and the 210 survival cases of serious HFMD, which were matched by gender and resident places with a ratio at 2:1 in the same period in Hunan were selected as control group. The basic information, hospitalized experience and previous medical history had been surveyed and the relevant risk factors were analyzed by single factor and multi factor logistic regression. RESULTS: In case group, 79.05% (83/105) of the cases lived in rural area and 9.52% (10/105) of the cases lived in urban-rural midst area. In control group, 87.62% (184/210) of the cases lived in rural area and 11.43% (24/210) of the cases lived in urban-rural midst area. In case group, 59.05% (62/105) of the patients first visited rural (private) clinics and 20.00% (21/105) first visited community hospitals in villages and towns; while in control group, 43.81% (92/210) and 13.33% (28/210) chose rural (private) clinics and community hospitals in villages and towns as the first choice respectively.22.86% (24/105) of the case group and 39.05% (82/210) of the control group were diagnosed as HFMD in their first visit to hospital.27.62% (29/105) of the case group and 7.14% (15/210) in control group were provided pyrazolone in the treatment. For glucocorticoid, 80.95% (85/105) and 5.71% (6/105) of the case group were given as treatment by rural (private) clinics and community hospitals in villages and towns separately; while the proportions in the control group were 41.43% (87/210) and 0.48% (1/210) respectively. For antibiotics, 35.24% (37/105) and 23.81% (25/105) of the case group were prescribed by rural (private) clinics and community hospitals in villages and towns separately; while the percentages in the control group were 15.71% (33/210) and 7.14% (15/210). 3.81% (4/105) of the case group and 11.90% (25/210) of the control group were vaccinated in one month before the onset. The results of single-factor logistic regression indicated that living in rural areas (OR = 0.075, 95%CI: 0.016 - 0.343) and in rural-urban midst areas (OR = 0.069, 95%CI: 0.013 - 0.368), diagnosis of HFMD in the first visit to hospital (OR = 0.463, 95%CI: 0.271 - 0.788) and vaccination one month before the onset (OR = 0.293, 95%CI: 0.099 - 0.866) were four protective factors; while rural (private) clinics as the first choice (OR = 4.717, 95%CI: 1.891 - 11.767), community hospital in villages and towns as the first choice (OR = 5.250, 95%CI: 1.883 - 14.641), medication of pyrazolone (OR = 4.961, 95%CI: 2.520 - 9.766), medication of glucocorticoid in rural (private) clinics (OR = 6.009, 95%CI: 3.435 - 10.510) and in community hospital in villages and towns (OR = 12.667, 95%CI: 1.505 - 106.638), medication of antibiotics in rural (private) clinics (OR = 2.918, 95%CI: 1.690 - 5.040) and in community hospital in villages and towns (OR = 4.062, 95%CI: 2.036 - 8.108) were seven risk factors. The results of multi-factors logistic regression showed that medication of pyrazolone (OR = 2.311, 95%CI: 1.062 - 5.030), medication of glucocorticoid in rural (private) clinics (OR = 5.480, 95%CI: 3.039 - 9.880), medication of antibiotics in rural (private) clinics (OR = 2.430, 95%CI: 1.301 - 4.538) and medication of antibiotics in community hospitals in villages and towns (OR = 3.344, 95%CI: 1.477 - 7.569) were the risk factors of death of HFMD. CONCLUSION: The risk factors of HFMD deaths include the medication of pyrazolone, glucocorticoid and antibiotics by rural (private) clinics and medical institutions in villages and towns. The department concerned should revise the technical manual to standardize the medication of the above drugs. PMID- 22321591 TI - [Etiologic detection and epidemiological analysis of one suspected case of diphtheria in Guangdong province]. AB - OBJECTIVE: To clarify the diagnosis of one suspected case of diphtheria in Guangdong province by epidemiological analysis and etiologic detection. METHODS: On July 6th 2010, the corynebacterium diphtheria was detected from the nasal secretions of one nasopharyngeal carcinoma patient in a college-town hospital in Guangzhou City, Guangdong Province. The patient and the close contacts were asked to participate in the epidemiological survey; and their nasopharyngeal swabs (3 samples) and the nasal secretions of the patient (1 sample) were collected. The bacteria of the samples were isolated and cultured by blood plate and agar loefflera. The smears of positive strains were dyed and identified by BioMerieux API Coryne biochemical card. Gene tox of beta-Corynebacteriophage, Corynebacterium diphtheriae was tested by PCR method, the aliphatic acid was analyzed by gas chromatography method and the Corynebacterium diphtheriae (CMCC 38009) was selected as positive control. RESULTS: The patient had not gone out, neither had been visited. The patient denied history of vaccines or the immunizations. From the survey on patient's family members and close contacts, no similar symptoms had been found. One strain of Corynebacterium diphtheriae was isolated from the patient's nasal secretions, Gram positive and shape diversified. After cultured by agar loefflera and Gram-dyed and Neisser-dyed, one end or both two ends of the strain showed typical metachromatic granule. API Coryne was identified to Corynebacterium diphtheriae mitis/belfanti (99.4%). The result of gas chromatography method also indicated Corynebacterium diphtheriae. No Corynebacterium diphtheriae was isolated from the nasopharyngeal swabs, neither of the patient nor of the close contacts. The gene tox of beta Corynebacteriophage, Corynebacterium diphtheriae was negative according to the PCR test. CONCLUSION: The isolated Corynebacterium diphtheriae did not produce toxin as there was no biological structure gene of toxin. The patient was a health carrier of nontoxic Corynebacterium diphtheriae. PMID- 22321592 TI - [Effect of highly active anti-retroviral therapy on prevention of mother to child transmission of HIV and on infant growth and development]. AB - OBJECTIVE: To identify the effect of highly active anti-retroviral therapy (HAART) on prevention of mother to child transmission (PMTCT) of HIV and on infant growth and development. METHODS: A total of 16 HIV-infected women or pregnant women selected in this study received HAART before or 18 - 24 weeks after pregnancy. The treatment included taking Zidovudine (AZT) 0.3 g each time, twice a day, Lamivudine (3TC) 0.3 g each time, once a day and Nevirapine (NVP) 0.2 g each time, twice a day or Efavirenz (EFV) 0.6 g each time, once a day, as well as labor intervention and artificial feeding. The growth index for 17 infants from HIV-infected mothers (experimental group) and 16 normal infants (control group) were observed for 18 months. Neonatal hemoglobin (Hb), liver and kidney function, serum iron and calcium were detected at neonatal period and at 12(th) month, respectively. RESULTS: All the pregnant women were in good conditions and had tolerance with HAART. The birth weight, length and Apgar score of the newborns in the experimental group were (3.5 +/- 0.9) kg, (54.2 +/- 3.8) cm and 7 - 10 scores respectively, however those in the control group were (3.6 +/- 0.8) kg, (55.6 +/- 3.6) cm and 8 - 10 scores (t(weight) = 1.01, t(length) = 6.98, P > 0.05). Weight and length of infants in experimental group were (9.36 +/ 1.8) kg and (76.3 +/- 2.7) cm at 12(th) month, while those in control group were (9.86 +/- 2.5) kg and (76.8 +/- 2.9) cm (t(weight) = 0.83, t(length) = 1.00, P > 0.05). The level of Hb in experimental group was (126.2 +/- 16.7) g/L, and was (148.6 +/- 20.5) g/L in control group (t = -5.89, P = 0.11). At 12(th) month, the levels of Hb and the total bilirubin (TB) were (125.9 +/- 19.8) g/L and (11.7 +/- 3.5) umol/L in experimental group; and those in the control group were (130.1 +/- 18.7) g/L and (13.2 +/- 3.7) umol/L (t(Hb) = -3.82, t(TB) = -2.14, P > 0.05). Serum iron and calcium were (25.4 +/- 5.7) umol/L and (26.4 +/- 7.2) umol/L at neonatal period and were (2.3 +/- 0.6) mol/L and (2.8 +/- 0.6) mol/L at 12(th) month in experimental group, while those were (26.2 +/- 4.9) umol/L and (28.1 +/- 6.9) umol/L at neonatal period and were (2.6 +/- 0.5) mol/L and (3.1 +/- 0.5) mol/L at 12(th) month in the control group (t(Fe) = 0.80 and t(Ca) = -3.00 in neonatal period, t(Fe) = -1.50 and t(Ca) = -1.00 at 12(th) month, P > 0.05). All infants of HIV-infected mothers were not infected with HIV when they were 18 months old. CONCLUSION: HAART can prevent mother to child transmission of HIV and it was not found to influence the baby's growth and development in this study. PMID- 22321593 TI - [Follow-up and outcome as well as the related biological factors on the cases with indeterminate HIV antibody level]. AB - OBJECTIVE: To explore the follow-up visit, outcome and auxiliary diagnosis method on the cases with indeterminate antibody level measured by Western blotting as well as the related biological factors. METHODS: The cases with indeterminate result were followed up according to the National Guideline for Detection of HIV/AIDS (2009) and samples were collected for HIV antibody detection, p24 antigen and nucleic acid were detected as a supplementary diagnosis at the same time. The samples were also be detected for HBV, HCV, TP, HTLV-I/II, ANA, and AFP, and the results were compared to that of screened positive and confirmed negative cases. RESULTS: A total of 73 were followed up successfully and taken a second HIV test, 25 cases were tested positive and 48 were tested negative for HIV during the follow-up period. For the 25 HIV positive cases, the HIV seroconversion rate was 100.00% at any time point when the interval between the first and returning detection was longer than 1 week. The major Western blotting bands for the cases with indeterminate result were p24 and gp160 and it was different between HIV positive and negative cases in Western blotting band profiles. The consistency and sensitivity of nucleic acid detection were higher than 90.00%, and were higher than that of p24 antigen (69.09% (38/55) and 27.27% (6/22)) (chi(2)(consistency) = 6.875, chi(2)(sensitivity) = 18.893, P < 0.05). The positive rates of ANA and AFP of indeterminate cases excluded from HIV infection were 20.83% (10/28) and 6.25% (3/48) and higher than that of screened positive and confirmed negative cases (0.00%), the difference had statistic significance (chi(2)(ANA) = 19.430, chi(2)(AFP) = 5.520, P < 0.05). CONCLUSION: It is critical to get timely diagnosis for the indeterminate cases according to the new national guideline for detection of HIV/AIDS. Nucleic acid detection has higher application value as auxiliary diagnosis for HIV infection than p24 antigen. The increased levels of ANA and AFP may be the factors resulting in the nonspecific indeterminate results. PMID- 22321594 TI - [Effect of plasma-derived hepatitis B vaccine 23(rd) year after a full course of vaccination in healthy young children]. AB - OBJECTIVE: The aim of the study was to evaluate the anti-HBs persistence and the long term preventive efficacy after vaccination 23 years with plasma-derived hepatitis B vaccine. METHODS: The study consisted of 261 children who were 5 - 9 years aged, from two primary schools in two townships of Xi'an. 126 children were randomly selected as vaccine group, and 135 children in control group. These children were followed up again in 2009. Excluding self-inoculation, the vaccine and control groups were 81 and 75, who was used to ask to recall details of their experience for vaccination and liver-related illnesses during past twelve years. Individuals who had anti-HBs titers less 10 mIU/ml, HBsAg, anti-HBc and HBV-DNA all were negative, were given a booster dose vaccine and retest for anti-HBs titer after one month. RESULTS: After eliminated the interference of an early booster dose and vaccination outside the study, the positive rate of anti-HBs was 48.1% (39/81) in the vaccine group at year 23, higher than 34.7% (26/75) in control group. At year 23 after primary vaccination, 84.0% (21/25) individuals in the vaccine group whose anti-HBs and anti-HBc both are negative showed a stronger anamnestic response after received a booster dose, while 7.5% (3/40) in the control group. At year 23 after primary vaccination, none clinical case of hepatitis B was found among 194 individuals. However, anti-HBc positive rate in the vaccine group was 16.0% (13/81), while the rate in the control group was 30.7% (23/75) (chi(2) = 4.687, P < 0.05). CONCLUSION: At 23 years after implemented a full course of plasma-derived hepatitis B vaccine, the recipients of vaccine were maintained anti-HBs at a high level or strong immunological memory. PMID- 22321595 TI - [Probabilistic evaluation of dietary exposure to lead and age-related exposure centile for residents in Jiangsu]. AB - OBJECTIVE: To establish a probabilistic model for evaluation of dietary exposure to lead and construct age-related exposure centiles for the residents in Jiangsu. METHODS: Lead contamination data were obtained from the national food contamination monitoring program during 2001 - 2006 and 2791 samples from 232 food products in Jiangsu were included. Food consumption data were from the national diet and nutrition survey conducted in 2002, including 3938 subjects in Jiangsu. A non-parametric probabilistic model using Monte Carlo simulation was applied to derive the intake distribution. The intake data was then analyzed using the LMS method, which constructs exposure percentiles adjusted for the median (M), the coefficient of variation (S) and the skewness (L) of the intake distribution. RESULTS: The median and P(99) of the lead exposure for the residents in Jiangsu were 1.02 ug*kg(-1)*d(-) and 9.29 ug*kg(-1)*d(-1), respectively.6.38% of the total population showed to have a lead intake exceeding the tolerable limit, which for the urban and rural population were 4.31% and 7.06%, respectively. The exceeding rate for children of 2 - 10 years old from the urban and rural areas were 13.17% and 17.70%, respectively. CONCLUSION: There was a large variation in the lead exposure level of the population in Jiangsu; People in rural areas are in greater risk for higher lead exposure than urban people; The dietary exposure to lead for children and the high-end population was serious. PMID- 22321596 TI - [The effects of tea polyphenols on the injury of fibrinolytic functions induced by high-methionine dietary in rats]. AB - OBJECTIVE: To study the protective impact of tea polyphenols (TP) on the injury of fibrinolytic functions induced by high-methionine dietary in rats. METHODS: 50 male Wistar rats were divided by stratified based on body weight into 5 groups with 10 in each group: namely control group, model group, low-dose TP group, medium-dose TP group and high-dose TP group. The rats in model group and TP groups were fed with 3% methionine dietary, control group rats with routine diet. In addition, rats in low-dose, medium-dose and high-dose TP groups were treated with TP at 50, 100 and 200 mg/kg dosage respectively by gavages every day, control group and model group rats were given with same amount distilled water. The animals were sacrificed after 8 weeks. The levels of tissue-type plasminogen activator (t-PA) and type-1 plasminogen activator inhibitor (PAI-1) in plasma were determined by ELISA assays, mRNA levels of t-PA and PAI-1 in aortic arch were detected by RT-PCR, t-PA and PAI-1 expression in aortic arch were detected by immunohistochemistry strept-avidin-biotin complex (SABC). RESULTS: After experiment, the t-PA expression of aortic arch in control group, model group, low dose TP group, medium-dose TP group and high-dose TP group were 133.03 +/- 10.14, 95.46 +/- 11.08, 111.97 +/- 11.91, 130.23 +/- 10.80, 139.39 +/- 9.41 (F = 14.15, P < 0.01), respectively, and the PAI-1 expression were 90.91 +/- 8.67, 166.76 +/- 12.18, 139.63 +/- 12.71, 134.66 +/- 13.19, 109.49 +/- 10.82 (F = 31.44, P < 0.01). The t-PA concentration of plasma were (10.69 +/- 1.26), (6.13 +/- 0.92), (8.56 +/- 1.19), (9.69 +/- 0.92), (11.97 +/- 1.08) ng/ml, respectively (F = 41.98, P < 0.01), and the PAI-1 concentration of plasma were (6.31 +/- 0.81), (16.98 +/- 1.27), (11.39 +/- 0.82), (8.46 +/- 0.67), (8.08 +/- 0.91) ng/ml, respectively (F = 207.74, P < 0.01). The mRNA levels of t-PA in aortic arch were 1.12 +/- 0.02, 0.75 +/- 0.14, 1.01 +/- 0.09, 0.95 +/- 0.08, 1.05 +/- 0.13 (F = 5.77, P < 0.05), and the mRNA levels of PAI-1 in aortic arch were 1.25 +/- 0.11, 1.74 +/- 0.06, 1.23 +/- 0.05, 1.09 +/- 0.14, 1.23 +/- 0.04 (F = 23.56, P < 0.01). CONCLUSION: The results indicate that TP seems to have regulatory function on transcription and protein levels of t-PA and PAI-1, in addition to maintaining the balance between PAI-1 and t-PA and healing the injury of fibrinolytic functions in rats induced by high-methionine dietary. PMID- 22321597 TI - [Trends of maternal mortality ratio during 1996-2010 in China]. AB - OBJECTIVE: To analyze time trend and regional disparities in maternal mortality ratio (MMR) and major causes of maternal death in China from 1996 to 2010. METHODS: Data used in this study were based on national maternal mortality surveillance system. From 1996 to 2005, it included 176 monitoring districts (countries) in 31 provinces, autonomous regions and municipalities in the inner land. From 2006 to the present, it covered 336 districts (countries). MMR, major causes of maternal death and their reduction margin, average annual reduction rate in different times and regions from 1996 to 2010 were analyzed. The trend and regional differences in MMRs and major causes of mortality were analyzed using Cochran-Armitage trend and Poisson Test. RESULTS: From 1996 to 2010, Chinese MMR has decreased by 53.2% from 64.7 in 1996 to 30.0 per 100 000 live births in 2010. MMR was higher in rural areas (30.1/100 000) than in urban areas (29.7/100 000), and highest in the west region (46.1/100 000) followed by the middle region (29.1/100 000) and the east region (17.8/100 000) in 2010. MMR in east, middle and west regions have decreased by 37.76%, 57.02% and 66.27% respectively from 1996 to 2010. The disparities between different regions were decreasing. From 2006 to 2010, MMR in rural areas has dropped to 1.82 times of the city, and that in the west was 3 times of the east. Obstetric hemorrhage was still the leading cause of maternal death, responsible for 47.9% maternal deaths in 1996 and 27.8% in 2010. The risk of death due to obstetric hemorrhage was decreasing. CONCLUSION: The MMR in China showed the decreasing trends. Although the regional disparities were still remarkable, they demonstrated narrowing trends. Interventions on maternal death should be focused in rural areas and west regions. PMID- 22321598 TI - [Epidemiological analysis of maternal death in Beijing from 1995 to 2010]. AB - OBJECTIVE: To analysis the trend of maternal death time and explore the impact of the variety of death causes and birth place to maternal death time. METHODS: According to the data provided by Beijing Maternal and Children Health Hospital, the 372 death cases of pregnant and lying-in women from 1995 to 2010, a retrospective study was performed to analyze the death causes, maternal death time and the influencing factors. RESULTS: The MMR declined from 27.9 per 100 000 live births from 1995 to 2000 to 14.8 per 100 000 live births from 2006 to 2010, with a decline of 46.9%. Among the maternal death within 24 hours of delivery, 79.7% (106/133) died of obstetric hemorrhage, hypertensive disorder complicating pregnancy and amniotic fluid embolism. It took up 47.8% (64/134) from 1995 to 2000, reduced to 37.5% (45/120) from 2006 to 2010. At the same time, the maternal mortality ratio within 24 hours reduced from 40.2%(54/134) to 28.3% (34/120), the variation of death time was consistent with the causes of maternal mortality (chi2 = 59.109, P < 0.05). Indirect obstetric causes increased significantly from 2006 to 2010, 53.2% (33/62) of pregnant women with heart disease, cerebrovascular disease and pulmonary embolism died in prenatal or more than 120 hours postnatal. Among the maternal death delved in hospital, 29.0% (29/100) died within 24 hours, 52 cases delved at home or in private clinics, 43 cases (82.6%) died within 24 h postnatal. There were significant differences between birth place and death time (chi2 = 24.500, P < 0.05). CONCLUSION: Maternal death time changed from 24 hours of delivery to prenatal or postnatal a long time. The maternal mortality causes and hospital delivery is an important factor affecting maternal time. PMID- 22321599 TI - [Meta-analysis of intervention effects on obesity in Chinese pupils]. AB - OBJECTIVE: To comprehensively evaluate the effect of interventions on obesity in Chinese pupils. METHODS: A literature research was carried out in China National Knowledge Infrastructure, Wanfang Data, VIP Database for Chinese Technical Periodicals, PubMed and the Excerpts Medica Database (EMBASE) databases to collect articles published between 1979 and 2010 concerning the effect of interventions for preventing obesity in Chinese pupils. Rate difference (RD) of the rate of obesity as the evaluation indicator was selected to Meta-analyze the effect of interventions on obesity. There are total 215 articles, in which 211 articles were written in Chinese and other articles were written in English. RESULTS: 17 literatures were used for Meta-analysis by the uniform inclusion and exclusion criteria. The results showed that the RD of obesity rate for the students in the intervention group was 3% (95%CI: 1% - 5%) after the intervention. However, the RD of obesity rate for the students in the control group was -2% (95%CI: -4% - -1%) after the intervention. Results of stratified analysis for the RD of obesity rate showed that the obesity rate for the students in the intervention group were decreased significantly after the intervention of combined programs with health education, physical exercise and nutrition interventions with moderate intervention time (1 to 2 years), the RD (95%CI) of obesity rate were 5% (2% - 8%), 3% (1% - 4%), respectively. For the studies whose baseline obesity rates was insignificant difference between the intervention group and the control group, the obesity rate for the students in the intervention group was 4% (95%CI: -7% - -1%) lower than the obesity rate for the students in the control group after the intervention. CONCLUSION: Health education-based comprehensive intervention is effective on obesity prevention in Chinese pupils; combined intervention programs with moderate intervention time (1 to 2 years) were effective in improving efficiency of obesity prevention in pupils. PMID- 22321600 TI - The use of oxygen for delivery room resuscitation of newborn infants in non Western countries. AB - BACKGROUND: Using pure oxygen (PO) in neonatal resuscitation increases oxidative stress and mortality in full-term hypoxic infants. International neonatal resuscitation guidelines recommend air or blended oxygen for resuscitation regardless of gestational age but this requires education and equipment that may not be globally available. OBJECTIVE: To determine current neonatal resuscitation practices and availability of oxygen blending equipment in non-Western hospitals. DESIGN: 196 email addresses were obtained through perinatal societies representing 45 hospitals in 14 countries in Asia, Africa and the Middle East. RESULTS: 68 (34.6%) responses were received from all 14 countries. The majority (90%, n=61) of respondents were aware of recent guideline changes but continued to resuscitate with PO because of the lack of equipment and uncertainty about international guidelines (61%, n=41 for term, 44%, n=30 for preterm). Most (81%, n=55) believed that PO caused adverse effects in term neonates. The availability of oxygen blending equipment correlated significantly with the country's gross domestic product. CONCLUSION: The majority of the practitioners we surveyed in non-Western countries are aware of the most recent recommendations regarding oxygen use in neonatal resuscitation. However, lack of oxygen blending equipment remains a hindrance to the use of blended gas at resuscitation in low resource, non-western countries. Global guidelines from developed countries must take into account the resource limitations and implementation difficulties faced by countries with restricted resources, where the majority of the high-risk infants are born. PMID- 22321601 TI - Machine learning amplifies the effect of parental family history of Alzheimer's disease on list learning strategy. AB - Identification of preclinical Alzheimer's disease (AD) is an essential first step in developing interventions to prevent or delay disease onset. In this study, we examine the hypothesis that deeper analyses of traditional cognitive tests may be useful in identifying subtle but potentially important learning and memory differences in asymptomatic populations that differ in risk for developing Alzheimer's disease. Subjects included 879 asymptomatic higher-risk persons (middle-aged children of parents with AD) and 355 asymptotic lower-risk persons (middle-aged children of parents without AD). All were administered the Rey Auditory Verbal Learning Test at baseline. Using machine learning approaches, we constructed a new measure that exploited finer differences in memory strategy than previous work focused on serial position and subjective organization. The new measure, based on stochastic gradient descent, provides a greater degree of statistical separation (p = 1.44 * 10-5) than previously observed for asymptomatic family history and non-family history groups, while controlling for apolipoprotein epsilon 4, age, gender, and education level. The results of our machine learning approach support analyzing memory strategy in detail to probe potential disease onset. Such distinct differences may be exploited in asymptomatic middle-aged persons as a potential risk factor for AD. PMID- 22321602 TI - Cloning and characterization of a surface antigen CiSA-32.6 from Cryptocaryon irritans. AB - Cryptocaryon irritans is a ciliated parasite causing cryptocaryosis in marine fish. To isolate functional genes, a cDNA library of C. irritans trophonts was constructed and a gene designated CiSA-32.6 (GenBank ID: JF812643) was cloned and characterized. The full-length cDNA (1158 bp) encoded a deduced polypeptide of 330 amino-acid (aa) with a signal peptide of 22 aa. To express the ciliate gene, a truncated open reading frame (CiSA-32.6t) was synthesized to remove fragments encoding the signal peptide and hydrophobic C-terminal and to modify non universal genetic codes. CiSA-32.6t was subcloned into Escherichia coli DH5alpha strain using the pGEX-4T-1 vector and then expressed as a glutathione S transferase fusion protein (rCiSA-32.6t). Western blotting analysis showed that sera from mice immunized with rCiSA-32.6t reacted specifically with a native protein (32.6 kDa) in parasite lysates. Moreover, rCiSA-32.6t reacted specifically with sera from mice immunized with a C. irritans trophont lysate. Expression of the CiSA-32.6 gene in C. irritans was detected at all developmental stages by reverse transcriptase PCR and Western blotting analysis. This study provides the basis of further investigations into the pathogenic biology of C. irritans and the control of cryptocaryosis. PMID- 22321603 TI - Identification and expression analysis of goose-type lysozyme in half-smooth tongue sole (Cynoglossus semilaevis). AB - Lysozymes are considered to be potent innate immune molecules against the invasion of bacterial pathogens. The goose-type lysozyme is one of the three major distinct lysozyme types identified in the animal kingdom including teleosts. In this report, we identified, sequenced, and characterized the goose type lysozyme gene (CsGLys) from half-smooth tongue sole (Cynoglossus semilaevis). The full-length cDNA of CsGLys is 1191 bp in length from the transcription start site to polyadenylation site, including a 91 bp 5'-terminal untranslated region (UTR), a 452 bp 3'-terminal UTR and a 648 bp open reading frame (ORF) of encoding a polypeptide with 215 amino acids. The deduced amino acid sequence of CsGLys possesses a Goose Egg White Lysozyme (GEWL) domain with three conserved residues (E91, D104 and D121) essential for catalytic activity. The CsGLys gene consisting of 2535 bp, was similar to those of other teleost species such as Japanese flounder and large yellow croaker with five exons interrupted by four introns. The 5'-flanking region of CsGLys gene shows several transcriptional factor binding sites related to immune response. Tissue expression profile analysis by quantitative real-time reverse transcription PCR showed that CsGLys mRNA was constitutively expressed in all examined tissues with the predominant expression in skin and the weakest expression in heart. The expression of CsGLys after challenged with bacteria Vibrio anguillarum was up regulated in blood, head kidney, liver and spleen at 12 h post-infection and it reached the peak level at the same time point with a 19.89-, 4.21-, 14.45- and 10.37-fold increase, respectively, while the CsGLys expression was down-regulated to lower level than the normal level in each tested tissues except in liver from the 48 h until 96 h. These results suggest that CsGLys might play an important role in half-smooth tongue sole host defense against the bacteria infection. PMID- 22321604 TI - Monocytes conditioned media stimulate fibronectin expression and spreading of inflammatory breast cancer cells in three-dimensional culture: A mechanism mediated by IL-8 signaling pathway. AB - BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer characterized by invasion of carcinoma cells into dermal lymphatic vessels where they form tumor emboli over expressing adhesion molecule E cadherin. Although invasion and metastasis are dynamic processes controlled by complex interaction between tumor cells and microenvironment the mechanisms by which soluble mediators may regulate motility and invasion of IBC cells are poorly understood. The present study investigated the effect of media conditioned by human monocytes U937 secreted cytokines, chemokines and growth factors on the expression of adhesion molecules E-cadherin and fibronectin of human IBC cell line SUM149. Furthermore, cytokines signaling pathway involved were also identified. RESULTS: U937 secreted cytokines, chemokines and growth factors were characterized by cytokine antibody array. The major U937 secreted cytokines/chemokines were interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1/CCL2). When SUM149 cells were seeded in three dimensional (3D) models with media conditioned by U937 secreted cytokines, chemokines and growth factors; results showed: 1) changes in the morphology of IBC cells from epithelial to migratory spindle shape branched like structures; 2) Over-expression of adhesion molecule fibronectin and not E-cadherin. Further analysis revealed that over expression of fibronectin may be mediated by IL-8 via PI3K/Akt signaling pathway. CONCLUSION: The present results suggested that cytokines secreted by human monocytes may promote chemotactic migration and spreading of IBC cell lines. Results also indicated that IL-8 the major secreted cytokine by U937 cells may play essential role in fibronectin expression by SUM149 cells via interaction with IL-8 specific receptors and stimulation of PI3K/Akt signaling pathway. PMID- 22321605 TI - BmaC, a novel autotransporter of Brucella suis, is involved in bacterial adhesion to host cells. AB - Brucella is an intracellular pathogen responsible of a zoonotic disease called brucellosis. Brucella survives and proliferates within several types of phagocytic and non-phagocytic cells. Like in other pathogens, adhesion of brucellae to host surfaces was proposed to be an important step in the infection process. Indeed, Brucella has the capacity to bind to culture human cells and key components of the extracellular matrix, such as fibronectin. However, little is known about the molecular bases of Brucella adherence. In an attempt to identify bacterial genes encoding adhesins, a phage display library of Brucella suis was panned against fibronectin. Three fibronectin-binding proteins of B. suis were identified using this approach. One of the candidates, designated BmaC was a very large protein of 340 kDa that is predicted to belong to the type I (monomeric) autotransporter family. Microscopy studies showed that BmaC is located at one pole on the bacterial surface. The phage displaying the fibronectin-binding peptide of BmaC inhibited the attachment of brucellae to both, HeLa cells and immobilized fibronectin in vitro. In addition, a bmaC deletion mutant was impaired in the ability of B. suis to attach to immobilized fibronectin and to the surface of HeLa and A549 cells and was out-competed by the wild-type strain in co-infection experiments. Finally, anti-fibronectin or anti-BmaC antibodies significantly inhibited the binding of wild-type bacteria to HeLa cells. Our results highlight the role of a novel monomeric autotransporter protein in the adhesion of B. suis to the extracellular matrix and non-phagocytic cells via fibronectin binding. PMID- 22321606 TI - Effect of genetic variation in the MHC Class II DRB region on resistance and susceptibility to Johne's disease in endangered Indian Jamunapari goats. AB - The pathogenesis of Johne's disease (JD), caused by Mycobacterium avium subsp. paratuberculosis (MAP), is complex and has not been completely understood yet. In the present study, we analysed the polymorphism in the exon-2 of the caprine major histocompatibility complex (MHC) Class II DRB region and its association with resistance or susceptibility to JD. A total of 203 Jamunapari goats, which is an Indian endangered breed highly susceptible to JD, kept at a single farm were studied. On the basis of clinical signs, microscopic examination, faecal culture, ELISA and diagnostic PCR, 60 and 143 goats were classified as resistant and susceptible to JD, respectively. PCR-based restriction fragment length polymorphism (PCR-RFLP) with two enzymes, PstI and TaqI, was used to assess variation in the DRB gene(s) in all 203 goats studied. Two di-allelic single nucleotide polymorphisms (SNPs), here referred as 'P' and 'T', were tested. In each of them, three genotypes were found in the group analysed. The minimum allele frequencies (MAFs) were 0.233 and 0.486 for the P and T SNPs, respectively. Statistically significant associations between alleles, individual genotypes and composed genotypes of both SNPs were found. The frequency of p and t alleles, of individual pp and tt and of composed pptt genotypes were significantly higher (P(corr) < 0.001) in the 'resistant' group as compared to the 'susceptible' group, while the P and T alleles were associated with susceptibility (P(corr) < 0.001). In heterozygous genotypes, susceptibility was dominant over resistance. The effects of both SNP on resistance and susceptibility were comparable and composed heterozygous genotypes showed intermediate levels of susceptibility in terms of the odds ratio and P-values calculated. PMID- 22321607 TI - Bayesian inference for genomic imprinting underlying developmental characteristics. AB - The identification of imprinted genes is becoming a standard procedure in searching for quantitative trait loci (QTL) underlying complex traits. When a developmental characteristic such as growth or drug response is observed at multiple time points, understanding the dynamics of gene function governing the underlying feature should provide more biological information regarding the genetic control of an organism. Recognizing that differential imprinting can be development-specific, mapping imprinted genes considering the dynamic imprinting effect can provide additional biological insights into the epigenetic control of a complex trait. In this study, we proposed a Bayesian imprinted QTL (iQTL) mapping framework considering the dynamics of imprinting effects and model multiple iQTLs with an efficient Bayesian model selection procedure. The method overcomes the limitation of likelihood-based mapping procedure, and can simultaneously identify multiple iQTLs with different gene action modes across the whole genome with high computational efficiency. An inference procedure using Bayes factors to distinguish different imprinting patterns of iQTL was proposed. Monte Carlo simulations were conducted to evaluate the performance of the method. The utility of the approach was illustrated through an analysis of a body weight growth data set in an F(2) family derived from LG/J and SM/J mouse stains. The proposed Bayesian mapping method provides an efficient and computationally feasible framework for genome-wide multiple iQTL inference with complex developmental traits. PMID- 22321608 TI - The yin and yang of viruses and interferons. AB - Interferons (IFNs)-alpha/beta are critical effectors of the innate immune response to virus infections. Through activation of the IFN-alpha/beta receptor (IFNAR), they induce expression of IFN-stimulated genes (ISGs) that encode antiviral proteins capable of suppressing viral replication and promoting viral clearance. Many highly pathogenic viruses have evolved mechanisms to evade an IFN response and the balance between the robustness of the host immune response and viral antagonistic mechanisms determines whether or not the virus is cleared. Here, we discuss IFNs as broad-spectrum antivirals for treatment of acute virus infections. In particular, they are useful for treatment of re-emerging virus infections, where direct-acting antivirals (DAAs) have limited utility due to DAA resistant mutations, and for newly emerging virus strains in which the time to vaccine availability precludes vaccination at the onset of an outbreak. PMID- 22321609 TI - Effects of doxycycline on gene expression in Wolbachia and Brugia malayi adult female worms in vivo. AB - BACKGROUND: Most filarial nematodes contain Wolbachia symbionts. The purpose of this study was to examine the effects of doxycycline on gene expression in Wolbachia and adult female Brugia malayi. METHODS: Brugia malayi infected gerbils were treated with doxycycline for 6-weeks. This treatment largely cleared Wolbachia and arrested worm reproduction. RNA recovered from treated and control female worms was labeled by random priming and hybridized to the Version 2- filarial microarray to obtain expression profiles. RESULTS AND DISCUSSION: Results showed significant changes in expression for 200 Wolbachia (29% of Wolbachia genes with expression signals in untreated worms) and 546 B. malayi array elements after treatment. These elements correspond to known genes and also to novel genes with unknown biological functions. Most differentially expressed Wolbachia genes were down-regulated after treatment (98.5%). In contrast, doxycycline had a mixed effect on B. malayi gene expression with many more genes being significantly up-regulated after treatment (85% of differentially expressed genes). Genes and processes involved in reproduction (gender-regulated genes, collagen, amino acid metabolism, ribosomal processes, and cytoskeleton) were down regulated after doxycycline while up-regulated genes and pathways suggest adaptations for survival in response to stress (energy metabolism, electron transport, anti-oxidants, nutrient transport, bacterial signaling pathways, and immune evasion). CONCLUSIONS: Doxycycline reduced Wolbachia and significantly decreased bacterial gene expression. Wolbachia ribosomes are believed to be the primary biological target for doxycycline in filarial worms. B. malayi genes essential for reproduction, growth and development were also down-regulated; these changes are consistent with doxycycline effects on embryo development and reproduction. On the other hand, many B. malayi genes involved in energy production, electron-transport, metabolism, anti-oxidants, and others with unknown functions had increased expression signals after doxycycline treatment. These results suggest that female worms are able to compensate in part for the loss of Wolbachia so that they can survive, albeit without reproductive capacity. This study of doxycycline induced changes in gene expression has provided new clues regarding the symbiotic relationship between Wolbachia and B. malayi. PMID- 22321610 TI - Monitoring of tumour progression using bioluminescence imaging and computed tomography scanning in a nude mouse orthotopic model of human small cell lung cancer. AB - Human small cell lung carcinoma (SCLC) is the most aggressive type of lung cancer but no clinically relevant animal model has been developed to date. Such a model would be valuable to study the molecular aspects of tumour progression and to test the effectiveness of new treatment agents. We generated a reproducible and reliable nude mouse orthotopic model of human SCLC with NCI-H209 tumour cells genetically modified to express firefly luciferase. Cells were analysed for long term stability of bioluminescence and a clone was passaged twice subcutaneously to enhance tumorigenicity. Cells resuspended in Matrigel and/or EDTA RPMI medium containing a (99m)Tc-labelled tin colloid used as tracer were implanted intrabronchially with a catheter inserted into the trachea and positioned in the main bronchus using X-ray-guided imaging. Deposition of cells into the lung was then assessed by scintigraphy. The growth of the primary tumour was sensitively and non-invasively followed by bioluminescence imaging that allowed real-time monitoring of tumour progression in the same animals over a 2-12-week period. Additional 3D bioluminescence imaging and computed tomography scanning were used to document tumour location and measurements that were confirmed by histological analyses. In conclusion, this original nude mouse orthotopic model resembles various stages of human small cell lung cancer, and therefore could be used to evaluate new treatment strategies. PMID- 22321611 TI - Prognostic studies of mammary and other neoplasia in veterinary medicine: a new paradigm. PMID- 22321612 TI - Immunophenotypic evaluation of working Labrador Retrievers and German Shepherd dogs living in the same environment. AB - Multiparametric flow cytometry was used to compare peripheral blood lymphocyte subset distribution between healthy working police Labrador Retrievers (LRs; n=12) and German Shepherd dogs (GS; n=11) living in the same environment. The CD4/CD8 ratio was significantly higher in LR than in GS because of the lower percentage of CD8+ T lymphocytes in LR. GS showed the highest relative percentage of CD3-/CD21- lymphocytes, whereas LR had the highest percentages of MHC II+ lymphocytes. Because age, sex, environmental and housing conditions, dietary patterns, and training or working routines were similar in both breeds in the study, differences in peripheral blood lymphocyte subset distribution could be attributed to the influence of breed on the immune system. PMID- 22321613 TI - Five patellar proximodistal positioning indices compared in clinically normal Greenland sled dogs. AB - Patellar luxation in large-breed dogs is associated with abnormal proximodistal patellar positioning. Using a clinically normal population of Greenland sled dogs, measurement reliability and the effect of limb position were compared for five patellar proximodistal positioning indices based on the Insall-Salvati (IS), modified Insall-Salvati (mIS), de Carvalho (dC), patellotrochlear (PT) and Blackburne-Peel (BP) indices. Indices were measured at one knee angle in 44 dogs and two knee angles in 10 dogs. Index susceptibility to error was modelled for different errors in knee angle estimation. Two reported techniques for determining knee angle were compared in a fox hind limb model. Indices dC and PT were significantly affected by knee angle (P<0.001). Error susceptibility was the lowest for IS and the greatest for PT. Intra- and inter-observer agreements were moderate to substantial for all indices. Measurement precision was good for all indices except BP. Patellar ligament laxity significantly affected IS, mIS, dC and BP (P<0.05). Knee angle measurements were technique dependent, with a bias of 9 degrees to 13 degrees and limits of agreement of +/-5 degrees . All five indices were reliable, but precision varied. For pre- and post-operative comparison, dC showed less error susceptibility than PT and better precision than BP. An ideal index for clinical use remains to be defined; the best option is dC, although with limitations. The method of knee angle measurement must be defined prior to index measurement and comparison of index values. Index values may vary with species and/or body size. PMID- 22321614 TI - Excising squamous cell carcinomas: comparing the performance of GPs, hospital skin specialists and other hospital specialists. AB - BACKGROUND: GPs have no defined role in the excision of squamous cell carcinomas (SCCs). Current guidelines recommend that all skin lesions suspicious of SCC should be referred urgently to secondary care. Evidence regarding current management of SCC in primary care is limited. Existing audit data suggest that up to 10% of SCCs may be excised in primary care. GPs may be able to have a greater role in the management of SCC but more evidence is required before this can be advocated. OBJECTIVE: To compare the practice of GPs, skin specialists (dermatologists and plastic surgeons) and other hospital specialists in excising SCCs. Methods . A retrospective analysis of all SCCs excised in the Grampian region between 1 January and 31 December 2005. A total of 1184 reports were rated for source and adequacy of excision. RESULTS: GPs excised 23.7% of all SCC positive biopsies. Whether the biopsy had been performed by a GP or a hospital skin specialist made no significant difference to excision adequacy. However, GPs were significantly more likely to excise adequately than hospital non-specialists (P < 0.001). Infrequent GP excisers appear to perform as well as frequent excisers in adequately excising SCCs. CONCLUSIONS: GPs excise a considerable number of SCCs in primary care. GPs compare favourably to skin specialists in excising SCCs. The performance of infrequent GP excisers does not appear to differ significantly from that of frequent GP excisers. Further work is required to define more clearly the role of GPs in the management of SCCs. PMID- 22321615 TI - Targeted delivery to monocytes. PMID- 22321616 TI - The Janus face of reactive oxygen species in resistance and susceptibility of plants to necrotrophic and biotrophic pathogens. AB - Plant pathogens can be divided into biotrophs and necrotrophs according to their different life styles; biotrophs prefer living, while necrotrophs prefer dead cells for nutritional purposes. Therefore tissue necrosis caused by reactive oxygen species (ROS) during pathogen infection increases host susceptibility to necrotrophic, but resistance to biotrophic pathogen. Consequently, elevation of antioxidant capacity of plants enhances their tolerance to development of necroses caused by necrotrophic pathogens. Plant hormones can strongly influence induction of ROS and antioxidants, thereby influencing susceptibility or resistance of plants to pathogens. Pathogen-induced ROS themselves are considered as signaling molecules. Generally, salicylic acid (SA) signaling induces defense against biotrophic pathogens, whereas jasmonic acid (JA) against necrotrophic pathogens. Furthermore pathogens can modify plant's defense signaling network for their own benefit by changing phytohormone homeostasis. On the other hand, ROS are harmful also to the pathogens, consequently they try to defend themselves by elevating antioxidant activity and secreting ROS scavengers in the infected tissue. The Janus face nature of ROS and plant cell death on biotrophic and on necrotrophic pathogens is also supported by the experiments with BAX inhibitor-1 and the mlo mutation of Mlo gene in barley. It was found that ROS and elevated plant antioxidant activity play an important role in systemic acquired resistance (SAR) and induced systemic resistance (ISR), as well as in mycorrhiza induced abiotic and biotic stress tolerance of plants. PMID- 22321617 TI - Is thromboembolism prophylaxis necessary for low and moderate risk patients in maxillofacial trauma? A retrospective analysis. AB - This study was designed to investigate retrospectively the incidence of venous thromboembolism (VTE) and the need for thromboembolism prophylaxis in patients undergoing surgery for oral and maxillofacial trauma. Data were obtained from all patients treated under general anaesthesia for maxillofacial trauma between January 2000 and January 2009 in the Department of Oral and Maxillofacial Surgery of the VU University Medical Center, Amsterdam. Patients' records were reviewed for complaints and information related to deep venous thrombosis (DVT) and pulmonary embolism (PE). The patients were classified according to a risk classification, and the incidence of reported DVT and PE was calculated. None of the patients received any form of thromboembolism prophylaxis. Of the 479 patients included in this study, one presented with VTE (0.2%). This male patient was treated for a panfacial trauma and was classified as high risk. From all analysed parameters only surgery time classification proved to have a significant relationship with VTE. PMID- 22321618 TI - Evaluation of the three-dimensional soft tissue changes after anterior segmental maxillary osteotomy. AB - The aim of this study was to assess the three-dimensional soft tissue changes following anterior segmental maxillary osteotomy, in terms of magnitude and direction in correlation to hard tissue changes, using cone beam computed tomography (CBCT). The study included 6 patients (age range 17-35 years) suffering from dental maxillary protrusion that required surgical correction by anterior segmental maxillary osteotomy. For each patient, preoperative and postoperative CBCT, photographs, and orthodontic casts were taken before and 6 months after operation to analyse soft tissue changes, in terms of magnitude and direction in correlation to hard tissue changes, using linear and angular measurements. Hard and soft tissue changes were only observed in the maxillary region, upper lip area and nasal tip. Soft tissue mean change included 53% backward displacement of the labrale superius in relation to bone displacement and 18.7% mean increase in the naso-labial angle. The highest correlation coefficient was obtained between the hard and soft tissue changes in the upper lip region. Anterior segmental maxillary osteotomy might be recommended as the treatment modality of choice in patients with maxillary or dento-alveolar protrusion, the technique is simple, safe, and postoperative complications are minimal. PMID- 22321619 TI - Improving endoscopic ultrasound-guided fine needle aspiration specimens in the absence of rapid onsite evaluation: does cytotechnologist training provide the solution? PMID- 22321620 TI - Epidemiology and management of oesophageal coin impaction in children. AB - OBJECTIVE: The epidemiology of oesophageal coin impaction in children is poorly understood. We aimed to assess characteristics of patients with coin impaction and identify predictors of type of coin impacted and management strategies. METHODS: Cases of coin impaction from 2002 to 2009 were identified by querying a tertiary care centre's billing, clinical, and endoscopy databases for the International Classification of Diseases, 9th Revision code "935.1 - foreign body in the oesophagus." Charts were reviewed to confirm case status and to extract pertinent data. RESULTS: Of 113 patients with oesophageal coin impaction (55% male; 45% Caucasian; mean age 2.9 years), 65 (58%) swallowed a penny, 85 (80%) had the impaction in the proximal oesophagus, and 103 (91%) required a procedure. Thirty-five (34%) patients had an upper endoscopy performed by a gastroenterologist and 68 (66%) had a laryngoscopy or oesophagoscopy performed by an otolaryngologist. Only 2 minor complications were noted. There was no significant relationship between the coin type and location of impaction, but 99% of cases performed by otolaryngologists were for proximally impacted coins, compared to 49% for gastroenterologists (p<0.001). CONCLUSIONS: Oesophageal coin impaction disproportionately affected young children and extraction was frequently required. Whilst pennies were the most commonly impacted coin, there were no clear predictors on impaction based on coin type. PMID- 22321621 TI - An unusual cause of haematemesis: left-sided portal hypertension due to a large pancreatic tumour. PMID- 22321622 TI - Platelet count/spleen diameter ratio for non-invasive diagnosis of oesophageal varices: is it useful in compensated cirrhosis? AB - AIM: To assess the diagnostic accuracy of the platelet count/spleen diameter ratio for identification of oesophageal varices and/or hypertensive gastropathy in patients with compensated cirrhosis. METHODS: Platelet count/spleen diameter ratio was calculated in 87 consecutive patients with compensated cirrhosis. A new cut-off with the highest sensitivity and specificity for the presence/absence of oesophageal varices and/or hypertensive gastropathy was identified. Performance of the platelet count/spleen diameter ratio considering previously reported cut off values were then tested in our population. RESULTS: A platelet count/spleen diameter ratio <936.4 had the best sensitivity and specificity for the diagnosis of oesophageal varices and for all endoscopic findings of portal hypertension. A value lower than 936.4 allowed identification of 64.5% of patients with oesophageal varices and 66.7% of patients with any sign of portal hypertension; a value higher than 936.4 excluded oesophageal varices in 64.3% of patients and any sign of portal hypertension in 68.6% of patients. CONCLUSIONS: In patients with compensated cirrhosis, the platelet count/spleen diameter ratio is not a useful parameter to avoid unnecessary upper endoscopy, independently of the cut-off. PMID- 22321623 TI - [In commemoration of Qian Yi-jian]. PMID- 22321624 TI - [The definition and rating system of oral leukoplakia (interim provisions)]. PMID- 22321625 TI - [The change of secretory leukocyte protease inhibitor and its correlation with elastase in the development of periodontal inflammation]. AB - OBJECTIVE: To investigate the change of secretory leukocyte protease inhibitor (SLPI) and elastase (EA) in the different stages of periodontal inflammation and to evaluate the possibility of the two proteins as saliva markers reflecting overall periodontal health status. METHODS: Unstimulated whole saliva were collected from 86 subjects (divided into 4 groups as healthy, gingivitis, moderate periodontitis and severe periodontitis). Fifteen patients with moderate or severe periodontitis were only given scaling and root planning (SRP). Whole saliva was collected and clinical patameters were recorded at baseline and four weeks after the treatment. SLPI concentrations were determined with enzyme linked immunosorbent assay (ELISA) systems, while EA with low-molecular-weight substrate reaction. RESULTS: There were no statistical differences of SLPI concentrations among four groups (P > 0.05). However, EA activities in moderate periodontitis and severe periodontitis groups [0.077 (0.060) and 0.077 (0.489)] were higher than in healthy and gingivitis group [0.058 (0.028) and 0.058 (0.024)] (P < 0.05). SLPI only showed a weak negative correlation with age (r = -0.301, P < 0.05), rather than with EA or clinical parameters. In 15 patients with chronic periodontitis the mean concentration of SLPI and EA activity was 2.031 (2.449) ug/L and 0.075 (0.118), and both decreased significantly to 1.405 (0.659) ug/L and 0.055 (0.028) respectively 4 weeks after SRP. CONCLUSIONS: After SRP, the decrease of SLPI concentration and EA activity in saliva may reflect the periodontal inflammation subsiding. SLPI in saliva was not correlated with the development of periodontal inflammation. PMID- 22321626 TI - [The preparation, identification and physicochemical properties of anti Porphyromonas gingivalis IgY]. AB - OBJECTIVE: To obtain egg yolk antibody in hen eggs laid by hens immunized with the protein of Porphyromonas gingivalis (Pg). To generate, purify IgY against Pg (anti-Pg-IgY) and identify its specificity. METHODS: PgATCC33277 was cultured under standard anaerobic conditions and harvested after proliferation. Then Pg was extracted by sonication until the cell pellets were shattered completely. After centrifugatiton, the supernatant was collected. Five-month-old Roman hens were immunized for egg antibody production. The antibody was inoculated intramuscularly and subcutaneously in the breast from multiple spot with 1.0 ml of a vaccine consisting of oil-adjuvant protein which was mixed with 1 ml protein of Pg and 1 ml Freund's adjuvant complete every 10 days, for 4 times. The eggs were collected after the first immunization and stored at 4 degrees C. The anti Pg-IgY was extracted and purified. The protein concentration was tested by bicinchoninic acid (BCA), the specificity of IgY analyzed by SDS polyacrylamide gel electrophoresis (SDS-PAGE), the titre of IgY and its physicochemical character were evaluated by indirect enzyme-linked immunosorbent assay. RESULTS: The concentration of obtained anti-Pg-IgY was 2.05 g/L. SDS-PAGE analysis of the anti-Pg-IgY showed that the molecular weight of IgY was consistent with the theoretical value. Protein of anti-Pg-IgY appeared approximately 5 days after the first immunization, and reached the peak at 50 - 55 days. Antibody titres reached 1:100 000. Each egg produced more than 10 mg IgY, and its purification was up to 95% as well. CONCLUSIONS: Layer hens immuned by Pg may provide specific IgY of high titre and high concentration. The antibody has high purity and is heat, acid and alkali-resistant. PMID- 22321627 TI - [Analysis of community composition in dental plaque of elder people with root caries]. AB - OBJECTIVE: To analyze the community in dental plaque of elder people with root caries. METHODS: Total DNAs were extracted from the root caries dental plaques of nine elders over 60 years of age. Polymerase chaid reaction-based denaturing gradient gel electrophoresis (PCR-DGGE) was used to analyze the microbial composition, DGGE bands were excised from the gels for sequencing and identification. RESULTS: The dominant genus in root caries dental plaque of elder people were: Acinetobacte [0.9% (1/114)], Actinobaculum [1.8% (2/114)], Actinomyces [15.8% (18/114)], Aggregatibacter [0.9% (1/114)], Capnocytophaga [14.0% (16/114)], Corynebacterium [0.9% (1/114)], Haemophilus [0.9% (1/114)], Mobiluncus [0.9% (1/114)], Naxibacter [0.9% (1/114)], Neisseriaceae [10.5% (12/114)], Porphyromonas [0.9% (1/114)], Prevotella [12.3% (14/114)], Selenomonas [6.1% (7/114)], Staphylococcus [1.8% (2/114)], Oralis streptococcus [6.1% (7/114)], Mutans streptococcu [7.9% (9/114)], Tannerella [0.9% (1/114)], Treponema [1.8% (2/114)], Veillonella [10.5% (12/114)] and two uncultured unknown genus [1.8% (2/114)]. Uncultred genotypes accounted for 19.30% of the total. Gram positive bacteria genotype accounted for 31.6% (36/114), and Gram-negative bacteria genotype accounted for 66.7% (76/114). CONCLUSIONS: There were many bacteria genotypes in root caries dental plaque in the elderly, which were widely distributed. Gram-negative bacteria accounted for the majority. Genotype-specific pathogenic bacteria were not found. PMID- 22321628 TI - [Comparative dosimetry of dental cone-beam computed tomography and multi-slice computed tomography for oral and maxillofacial radiology]. AB - OBJECTIVE: To compare the effective radiation dose levels of cone beam computed tomography (CBCT) with those of multi-slice computed tomography (MSCT) when scanning the same maxillofacial regions. METHODS: The effective doses of 2 CBCT (NewTom 9000 and DCT Pro) and 1 MSCT (bright speed edge select 8 slice) scanners were calculated using thermoluminescent dosimeters (TLD) that were placed in a head and neck phantom, and expressed according to the International Commission on Radiation Protection (ICRP) 2007 guidelines. RESULTS: Effective dose values ranged from 41.8 to 249.1 uSv for CBCT. The doses of MSCT scanning for maxilla, mandible and maxilla + mandible were 506.7, 829.9 and 1066.1 uSv, respectively. Dose levels of scanning only for maxilla or mandible were significantly lower than those for maxilla + mandible. CONCLUSIONS: When scanning the same maxillofacial regions, the dose levels for NewTom 9000 and DCT Pro CBCT images were lower than those for Bright speed edge select 8 slice MSCT images. Dose levels reduction could be obtained when smaller regions were scanned. PMID- 22321629 TI - [Establishment of the micro-stress sensor measurement system for invisible aligner technique]. AB - OBJECTIVE: To design and build the micro-stress sensor measurement system for invisible aligner technique. METHODS: A measurement system based on silicon-on insulator piezoresistive stress sensor was developed. A four-point-bending based experimental apparatus was constructed to calibrate the piezoresistive coefficients of this stress sensor. A chemical-mechanical polishing process was developed for thinning the stress sensor dies. A packaging solution using flexible printed circuit to get signals out was designed. RESULTS: The developed silicon stress sensor chip was 7.0 mm * 6.0 mm * 0.1 mm in size, and 13 sensor rosettes and 4 calibration rosettes were fabricated in one sensor. And a main testing PCB and a Lab View program were designed to carry out the automation measurement of the stress sensor. The stress state during the process was obtained through this test system. And measuered the stress of the 13 sensor unit. CONCLUSIONS: A stress measurement system was established for measuring stress during orthodontic treatment with invisable aligner. PMID- 22321630 TI - [Effect of diubiquitin gene silencing by small interfering RNA on proliferation and invasion of tongue carcinoma Tca8113 cells]. AB - OBJECTIVE: To study the effect of diubiquitin (FAT10) down-regulation by small interfering RNA-mediated RNA interference (RNAi) on the biological features of tongue carcinoma cell line Tca8113. METHODS: Tca8113 cells were transfected with synthetic small interfering RNA (siRNA) targeting FAT10. Expression of FAT10 mRNA and protein were respectively measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting, transfection efficiencies were monitored. The distribution of cell cycle phases was determined using flow cytometry. The proliferative and invasive ability of Tca8113 cells in vitro was evaluated by the colony-forming unit assay and Transwell migration assay respectively. RESULTS: Both FAT10 mRNA and protein expression were significantly decreased in the experimental group (pU-FAT10-siRNA: mRAN 0.36 +/- 0.03, Protein 0.39 +/- 0.04) compared with controls ( CONTROL: mRNA 0.95 +/- 0.05, Protein 0.69 +/- 0.05; pU siRNA: mRNA 0.92 +/- 0.07, Protein 0.64 +/- 0.05) (P < 0.05). The cell cycle was arrested in the G(1) phase [pU-FAT10-siRNA: (72.45 +/- 5.81)%, CONTROL: (45.95 +/ 3.80)%, pU-siRNA: (45.95 +/- 3.80)%]. The proliferation and invasiveness of treated Tca8113 cells were inhibited in vitro (pU-FAT10-siRNA: 41.83 +/- 8.19, CONTROL: 317.21 +/- 69.48, pU-siRNA: 339.36 +/- 73.84). CONCLUSIONS: Delivery of siRNA targeting FAT10 seems efficient in down-regulating FAT10 expression and diminishing the growth, proliferation and invasiveness of Tca8113 cells, suggesting that siRNA-based strategy targeting FAT10 may lay a foundation for the clinical management of tongue carcinoma. PMID- 22321631 TI - [Experimental study on rat submandibular gland cell and silk fibroin-chitosan in vivo]. AB - OBJECTIVE: To evaluate the feasibility of the tissue engineered submandibular gland constructed in vivo based on submandibular gland cells and silk fibroin chitosan (SFCS). METHODS: Submandibular gland cells were obtained and purified. The second generation cells labeled by 5'-BrdU were seeded on SFCS(5 mm * 5 mm * 5 mm). Submandibular gland cells seeded on SFCS was implanted beneath the skin on the back. At 3, 7, 14 d post-implantation, implant sites were examined local and systemic responses. After paraffin embedding, serial sections 6 mm thick were cut and stained with either hematoxylin and eosin or brdu tissue stain for immunohistochemical studies and examined the responses of tissue. Scanning electron microscope was used to observe the growth behavior submandibular gland cells on SFCS scaffolds. RESULTS: General observation: at the 3, 7, 14 d after in vivo implantation, capsule formed in the surface of insert. Histological observation: in experimental group, submandibular gland cells proliferate on the SFCS scaffold fused to form unit 14 d after implantation. Brdu immunohistochemical observation: the results of labelled cells were positive by immunohistochemical method at each time point. Cytokeratin-8 (CK-8) immunohistochemical observation: the results of labelled cells were positive by immunohistochemical method at each time point. With time, the positive cells gradually increased. Scanning electron microscope: the shape of the SFCS scaffold was mesh. At earlier, submandibular gland cells presence in disorder at attach to the SFCS. At the 14 d submandibular gland cells proliferate on the SFCS scaffold and form functional unit. CONCLUSIONS: Such constructed tissue engineered submandibular gland based on submandibular gland cells and SFCS is promising. PMID- 22321632 TI - [Effect of surface treating methods on the shear strength of luting cements to Cercon zirconia]. AB - OBJECTIVE: To study the effect of surface treating methods on the shear strength of Panavia F luting cements to Cercon zirconia. METHODS: Forty sample disc of Cercon zirconia with 20 mm in diameter and 4 mm in height were prepared. Another 40 sample discs with 5 mm in diameter and 4 mm in height were also prepared Both of the two types of samples were randomly devided into four groups A, B, C, and D in which different surface treatments were delivered. In group A samples was treated with 600# sand paper, and in group Bwith sand blasting, and silanization in group C, and sand blasting plus silanization in group D. All samples were bonded with Panavia F luting cement under the aid of glass mould. The value of shear strength was measured and statistically analysed. RESULTS: The shear strength of four groups of samples were (21.50 +/- 1.98), (23.68 +/- 2.31), (20.69 +/- 1.55), (24.01 +/- 2.19) MPa respectively. The population mean was not equal. There was no significant difference between 600# sand paper treated group and silanization group, nor between sand blasting group and sand blasting plus silanization group. CONCLUSIONS: Sand blasting is a effective means to increase the shear strength, and 600# sand paper treatment and silanization can't increase the shear strength. PMID- 22321633 TI - [The support of National Natural Science Foundation of China prompts the progress and development of basic research of dental and craniofacial research: a 25 years review]. AB - OBJECTIVE: To investigate the effect of National Natural Science Foundation of China (NSFC) on the progress of dental research from 1986 to 2010. METHODS: The data regarding the NSFC allocated to dental and craniofacial research from 1986 to 2010 were collected. Total expenses and numbers of the majority of programs and the situation of completed program finished in recent 7 years were provided. RESULTS: From 1986 to 2010, a total of 922 projects and 204 401 thousands Chinese Yuan supported by NSFC were allocated to dental research. The detailed allocations were as follows: general program (564), young scientists fund (258), regional fund (40), key program (11), national science fund for distinguished young scholars (5), major international (regional) joint research program (1), others (43). The grants of talent training increased dramatically. Taking the projects (307) completed between 2003 and 2009 for example, 307 papers were published in Science Citation Index (SCI) included journals and 1049 papers were published on Chinese journals. By the time of completion of the projects, 39 post doctoral students, 590 students for PhD degree and 670 students for Master degree had been trained. CONCLUSIONS: Over the past 25 years, the continuous increase of NSF on dental research has led to substantial achievement, resulting in great progress of dental oral-cranio-facial research. PMID- 22321634 TI - [Summary of the 10th Chinese Orthodontic Conference]. PMID- 22321635 TI - [Problem solving in ednodontic diseases: IX. Risk factors and clinical diagnosis of vertical root fractures]. PMID- 22321636 TI - [Developmental abnormality of the teeth in children: I. The clinical treatment of the children with hypodontia in the mixed dentition]. PMID- 22321637 TI - [Clinical advance in the use of hyperbaric oxygen therapy in the prevention and management of osteoradionecrosis]. PMID- 22321638 TI - Olfactory impairment is associated with functional disability and reduced independence among older adults. AB - OBJECTIVES: Despite its relatively high prevalence, population-based data are lacking on whether olfactory impairment influences the functional status and independence of older adults. We assessed associations between olfactory impairment with activities of daily living (ADL) measures and the likelihood of using community support services and/or reliance on non-spouse family/friend support among older adults. STUDY DESIGN: Olfaction was measured using the San Diego Odor Identification Test (SDOIT) among 1636 participants of the Blue Mountains Eye Study (2002-4). Functional status was determined by the Older Americans Resources and Services ADL scale. Use of services and non-spouse family/friend support was self-reported. RESULTS: Use of community support services was reported by 15.2% and 5.2% of persons with and without olfactory impairment, respectively. After multivariable adjustment including for cognitive function, participants with compared to those without olfactory impairment were more likely to use community support services and non-spouse family/friend support, odds ratio, OR, 1.82 (95% confidence intervals, CI 1.16-2.86) and OR 1.62 (95% CI 1.14-2.32), respectively. ADL difficulty was reported by 16.9% (n=57) and 4.4% (n=45) of participants with and without olfactory loss, respectively. Olfactory impairment was associated with increased likelihood of experiencing ADL difficulty, multivariable-adjusted OR 1.98 (95% CI 1.10-3.57). Olfactory loss was significantly associated with impaired basic ADL, OR 1.57 (95% CI 1.12-2.20). CONCLUSIONS: The functional ability and independence of older adults is significantly impaired in the presence of olfactory impairment. Early diagnosis of olfactory loss by primary physicians and geriatricians could facilitate timely interventions assisting the maintenance of functional independence in later life. PMID- 22321639 TI - LAMC1 gene is associated with premature ovarian failure. AB - OBJECTIVES: Common variations with modest effect in complex and polygenic disease such as premature ovarian failure (POF) can be detected by a genome wide association study. We performed a genome wide association study to identify predisposing genes associated with an increased risk of POF. STUDY DESIGN: In stage I, genome wide association study was performed using 24 POF patients and 24 matched controls. A strongly associated region was re-tested to confirm the association with POF in stage II using 98 patients and 218 matched controls. RESULTS: In the stage I, we found a strongly associated region that was located on chromosome 1q31 and encoded the laminin gamma 1 (LAMC1) gene. All 22 single nucleotide polymorphisms (SNPs) in the LAMC1 formed a linkage disequilibrium block and two haplotypes were significantly associated with POF. In the stage II, 14 SNPs, the majority of which were SNPs located in coding region and tagging SNPs, were genotyped. Distributions of 9 SNPs of them including one nonsynonymous SNP (rs20558) and one haplotype (HT1, C-C-T-G-C-C-A-T-T-C) were significantly higher in POF patients than in control group (86.6% and 74.5%, respectively, OR=2.209, CI: 1.139-4.284, P=0.017). CONCLUSIONS: We showed for the first time that LAMC1 is significantly associated with POF, and specifically, possession of at least one HT1 was associated with susceptibility to POF. This result means that HT1 may co-exist with causative variant for susceptibility to POF in linkage disequilibrium and that the LAMC1 may be involved in POF pathogenesis. PMID- 22321640 TI - Can physical activity reduce excessive gestational weight gain? Findings from a Chinese urban pregnant women cohort study. AB - BACKGROUND: Excessive gestational weight gain (GWG) poses negative impact on mothers and their children. It is important to understand the modifiable lifestyle factors associated with excessive GWG during pregnancy to guide future public health practice. AIM: To investigate the association between physical activity during pregnancy and GWG of Chinese urban pregnant women. METHODS: A pregnant women cohort was established between 2005 and 2007 in Changzhou, China. Physical activity levels of pregnant women were assessed using pedometer in the 2nd and 3rd trimester, respectively. According to step counts, pregnant women were categorized into 4 different physical activity groups: Sedentary, Low Active, Somewhat Active and Active. The pregnant women were followed for eligibility and data collection from the 2nd trimester to delivery. Multiple linear regression and multiple binary logistic model were applied to determine the association between physical activity and GWG. RESULTS: Physical activity levels and GWG of 862 pregnant women were assessed, among them 473 (54.9%) experienced excessive GWG. The adjusted odds ratio (OR) was 0.59 (95%CI: 0.36 ~ 0.95) for excessive GWG in the Active group during the 2nd trimester and 0.66 (95%CI: 0.43 ~ 1.00) in the Somewhat Active group during the 3rd trimester, compared with the Sedentary group respectively. In the last two trimesters, the Active group had 1.45 kg less GWG, than the Sedentary group. The ORs of excessive GWG decreased with the increased level of physical activity (P < 0.05). CONCLUSION: This study suggests that pregnant women being physically active have less weight gain during pregnancy. PMID- 22321642 TI - Increased miR-222 in H. pylori-associated gastric cancer correlated with tumor progression by promoting cancer cell proliferation and targeting RECK. AB - Little is known about the potential role of microRNAs (miRNAs) in the carcinogenesis of gastric cancer induced by Helicobacter pylori (H. pylori). Here, we showed that microRNA-222 (miR-222) was up-regulated in H. pylori infected gastric mucosa and gastric cancer. Ectopic expression of miR-222 promoted cell proliferation and colony formation in vitro. Mechanistically, we identified RECK as a novel target of miR-222, and also confirmed their relationship by the inverse correlation of mRNA expression ex vivo. Furthermore, we found that RNA interference silencing of RECK can mimic the oncogenic effects of miR-222. Collectively, H. pylori may function as an initiator in the process of carcinogenesis by up-regulating miR-222, which further participates in the progression of cancer by promoting proliferation and inhibiting RECK. PMID- 22321641 TI - Two sides of the story? Smad4 loss in pancreatic cancer versus head-and-neck cancer. AB - TGFbeta signaling Smads (Smad2, 3, and 4) were suspected tumor suppressors soon after their discovery. Nearly two decades of research confirmed this role and revealed other divergent and cancer-specific functions including paradoxical tumor promotion effects. Although Smad4 is the most potent tumor suppressor, its functions are highly context-specific as exemplified by pancreatic cancer and head-and-neck cancer: in pancreatic cancer, Smad4 loss cannot initiate tumor formation but promotes metastases while in head-and-neck cancer Smad4 loss promotes cancer progression but also initiates tumor formation, likely through effects on genomic instability. The differing consequences of impaired Smad signaling in human cancers and the molecular mechanisms that underpin these differences will have important implications for the design and application of novel targeted therapies. PMID- 22321643 TI - Activation of spleen tyrosine kinase is required for TNF-alpha-induced endothelin 1 upregulation in human aortic endothelial cells. AB - Endothelin-1 (ET-1) promotes atherosclerosis. We tested whether spleen tyrosine kinase (Syk) mediates tumor necrosis factor-alpha (TNF-alpha)-induced ET-1 upregulation in human aortic endothelial cells (HAECs) and sought to identify the signal pathways involved. TNF-alpha-induced reactive oxygen species (ROS) activated Syk and phosphatidylinositol 3-kinase (PI3K), which was required for the activation of AP-1 and subsequent ET-1 gene transcription. ROS mediated c-Jun NH(2)-terminal kinase (JNK) is also required for AP-1 activation, but Syk and PI3K regulated AP-1 activation independently of JNK. Through regulation of ET-1 production, Syk could be implicated in atherosclerosis. PMID- 22321644 TI - Pro42 and Val45 of staphylokinase modulate intermolecular interactions of His43 Tyr44 pair and specificity of staphylokinase-plasmin activator complex. AB - Staphylokinase (SAK) forms a 1:1 stoichiometric complex with plasmin (Pm) and changes its substrate specificity to create a plasminogen (Pg) activator complex. The His(43)-Tyr(44) pair of SAK resides within the active site cleft of the partner Pm and generates intermolecular contacts to confer Pg activator ability to the SAK-Pm bimolecular complex. Site-directed mutagenesis and molecular modeling studies unravelled that mutation at 42nd or 45th positions of SAK specifically disrupts cation-pi interaction of His(43) with Trp(215) of partner Pm within the active site, whereas pi-pi interaction of Tyr(44) with Trp(215) remain energetically favoured. PMID- 22321645 TI - Bioluminescence imaging: looking beyond the light. AB - Bioluminescence imaging (BLI) enables in vivo imaging of molecular and cellular processes. It has gained in popularity over the past decade because of its easy translation from in vitro to in vivo experiments, its sensitivity, and its ease of use. However, experience in applying BLI in living subjects is still limited, and many researchers have encountered unexpected or biased BLI readout and reported important influencing factors. In this review, we summarize both the biological and physical effects that occur at the enzyme level or during light propagation towards the camera. The knowledge and detection of such factors, together with the development of new strategies and better BLI compounds, will improve the accuracy of the technique in the future. PMID- 22321646 TI - Dissociable roles of human inferior frontal gyrus during action execution and observation. AB - There has been recent controversy about whether activation in the human inferior frontal gyrus (IFG) and Brodmann Area (BA) 6 when observing actions indicates operation of mirror neurons. Recent functional magnetic resonance imaging (fMRI) data have demonstrated repetition suppression (RS) effects in posterior IFG which are consistent with the presence of mirror neurons in humans. Here we investigated whether there were similar RS effects elsewhere in the IFG and BA6, or whether, instead, activation in other locations may signal operation of alternative mechanisms. Replicating previous findings, we found RS effects in posterior IFG consistent with the operation of mirror neurons. However, these effects were not found in other locations in IFG and BA6. Additionally, activation patterns in anterior regions of IFG suggested dissociable operations when observing and executing actions. Therefore, caution should be exercised when claiming that activations in many locations during action observation indicate the operation of mirror neurons. Activation may instead reflect alternative mechanisms, such as encoding of the semantic features of actions. PMID- 22321647 TI - A comparison of long-term postconcussive symptoms between university students with and without a history of mild traumatic brain injury or orthopedic injury. AB - Mild traumatic brain injury (mild TBI) is often associated with postconcussive symptoms such as headache, memory problems, and irritability. However, high rates of similar symptoms in groups without a history of TBI raise questions about the clinical validity of the postconcussive syndrome. This study was conducted to address these issues through systematic examination of symptoms reported by those with and without a history of mild TBI or orthopedic injury. Responses to the Postconcussion Syndrome Checklist (PCSC), demographic information, and medical history were collected via online questionnaire from 3027 non-referred university students (2280 without a history of mild TBI or orthopedic injury, 491 with a history of orthopedic injury, and 256 with post-acute mild TBI). Although the mild TBI group reported higher mean levels of symptoms, confirmatory factor analyses demonstrated that symptoms clustered into parallel cognitive, somatic, affective, and sensory factors in all three groups. Despite modestly higher mean symptoms among those with a history of mild TBI, symptom clusters did not differ from non-TBI groups. These findings cast doubts about the clinical validity of the "postconcussive syndrome" and raise questions about pathways by which mild TBI and other factors may influence the expression of chronic symptoms. PMID- 22321648 TI - Response of the chromatophores in relation to the healing of skin wounds in an Indian Major Carp, Labeo rohita (Hamilton). AB - Chromatophores show significant changes during healing of skin wounds in Labeo rohita (Common Name--Rohu). Wound area can be divided into regions I, II and III. After infliction of wound, skin colour becomes significantly dark by 2h that is gradually restored by 2d. In regions II and III at 5 min, epidermal melanophores appear with beaded dendrites. In these regions at 2h and in region I at 6h, epidermal melanophores appear small, rounded or irregular shaped having dendritic processes with aggregated melanosomes. Subsequently, melanophores appear having elongated dendrites with dispersed or aggregated melanosomes. At 24h, clusters of pigmented bodies appear in regions I and II. These bodies increase up to 2d, and then diminish gradually and disappear by 8d. Changes in dermal melanophores in region II at 5 min indicate the onset of degeneration. Degenerating melanophores increase up to 12h, then gradually decline, and disappear by 4d. Simultaneously, stellate melanophore reappear, gradually increase and appear like control by 8d. Dermal melanophores in region III at different intervals appear stellate. In region I stellate dermal melanophores appear at 4d. Stellate melanophores in all regions show different distribution of dispersed or aggregated melanosomes. With the appearance of dermal melanophores, highly refractive, crystalline structures, possibly the refractive platelets of the iridophores, are visualized around them. At subsequent intervals, these are frequently observed. This study provides interesting insights in injury induced changes in chromatophores in fish. The findings could be considered useful in perception of intriguing features in the development of pigment research in future. PMID- 22321649 TI - The role of object functions for deferred imitation--do infants selectively retain and forget target actions? AB - The present study investigated the effect of target action functionality (functional vs. arbitrary actions) on 18- and 12-month-old infants' deferred imitation performance. While 18-month-olds' deferred imitation performance was assessed after a short (30 min) and after a long (2 weeks) delay, only the short delay was realized in 12-month-olds. Besides replicating the well established memory effect for both age groups, that is, an improved performance level of target actions in all memory tests as against to a baseline phase, a functionality effect was found, indicating that infants of both age groups imitated significantly more functional than arbitrary target actions. The rate of forgetting of target actions between the first and the second memory assessment was similar for functional and arbitrary actions, demonstrating that the forgetting process is not specific for the two types of target actions. Implications of the findings for both imitation and memory theories as well as for memory test construction are discussed. PMID- 22321651 TI - Erythroderma in the era of biological therapies. AB - Erythroderma is a scaling erythematous dermatitis involving 90% or more of the cutaneous surface. Psoriasis and eczema are the most common dermatoses underlying erythroderma. Cutaneous T cell lymphomas can also cause erythroderma. Differential diagnosis between psoriatic erythroderma and lymphomatous erythroderma is often challenging. Tumour necrosis factor-alpha inhibitors are a new class of drugs used in the treatment of psoriasis, even in erythrodermic psoriasis. The effects of anti-tumour necrosis factor-alpha in cutaneous T cell lymphomas have not yet been established. Consequently, it is mandatory to treat an erythrodermic psoriatic patient with tumour necrosis factor-alpha blockers only if a lymphoproliferative cutaneous disorder has been excluded. PMID- 22321652 TI - Identification of polymorphic inversions from genotypes. AB - BACKGROUND: Polymorphic inversions are a source of genetic variability with a direct impact on recombination frequencies. Given the difficulty of their experimental study, computational methods have been developed to infer their existence in a large number of individuals using genome-wide data of nucleotide variation. Methods based on haplotype tagging of known inversions attempt to classify individuals as having a normal or inverted allele. Other methods that measure differences between linkage disequilibrium attempt to identify regions with inversions but unable to classify subjects accurately, an essential requirement for association studies. RESULTS: We present a novel method to both identify polymorphic inversions from genome-wide genotype data and classify individuals as containing a normal or inverted allele. Our method, a generalization of a published method for haplotype data 1, utilizes linkage between groups of SNPs to partition a set of individuals into normal and inverted subpopulations. We employ a sliding window scan to identify regions likely to have an inversion, and accumulation of evidence from neighboring SNPs is used to accurately determine the inversion status of each subject. Further, our approach detects inversions directly from genotype data, thus increasing its usability to current genome-wide association studies (GWAS). CONCLUSIONS: We demonstrate the accuracy of our method to detect inversions and classify individuals on principled-simulated genotypes, produced by the evolution of an inversion event within a coalescent model 2. We applied our method to real genotype data from HapMap Phase III to characterize the inversion status of two known inversions within the regions 17q21 and 8p23 across 1184 individuals. Finally, we scan the full genomes of the European Origin (CEU) and Yoruba (YRI) HapMap samples. We find population-based evidence for 9 out of 15 well-established autosomic inversions, and for 52 regions previously predicted by independent experimental methods in ten (9+1) individuals 34. We provide efficient implementations of both genotype and haplotype methods as a unified R package inveRsion. PMID- 22321653 TI - Ecosystem restoration with teeth: what role for predators? AB - Recent advances highlight the potential for predators to restore ecosystems and confer resilience against globally threatening processes, including climate change and biological invasions. However, releasing the ecological benefits of predators entails significant challenges. Here, we discuss the economic, environmental and social considerations affecting predator-driven ecological restoration programmes, and suggest approaches for reducing the undesirable impacts of predators. Because the roles of predators are context dependent, we argue for increased emphasis on predator functionality in ecosystems and less on the identities and origins of species and genotypes. We emphasise that insufficient attention is currently given to the importance of variation in the social structures and behaviours of predators in influencing the dynamics of trophic interactions. Lastly, we outline experiments specifically designed to clarify the ecological roles of predators and their potential utility in ecosystem restoration. PMID- 22321654 TI - Homocysteine, folate, and vitamin B12 levels and vertebral fracture risk in postmenopausal women. AB - The objective of this study was to examine the influence of homocysteine, vitamin B(12), and folate on the prevalence of asymptomatic osteoporotic vertebral fractures (VFs) using vertebral fracture assessment (VFA) in postmenopausal women. The study cohort consisted of 188 consecutive postmenopausal women (mean age, weight, and body mass index of 57.9 +/- 8.5 [41-91]yr, 74.4 +/- 13.5 [38 150]kg, and 30.4 +/- 5.2 [17.1-50.7]kg/m(2), respectively). Lateral VFA images and scans of the lumbar spine and proximal femur were obtained using a Lunar Prodigy Vision densitometer (GE Healthcare Inc., Waukesha, WI). VFs were defined using a combination of Genant's semiquantitative approach and morphometry. Fifty eight (30.9%) patients had densitometric osteoporosis. VFs were identified using VFA in 76 (40.4%) patients: 61 women had grade 1 VFs and 15 had grade 2 or 3 VFs. No statistical difference was shown between the 3 groups (absence of VFs, VFs grade 1, and VFs grade 2/3) concerning the biological parameters. Comparison of patients according to quartiles of homocysteine levels showed that women in the highest quartile were older and had a lower bone mineral density (BMD); however, the prevalence of VFs was not statistically different from that of women in the other quartile groups. Stepwise regression analysis showed that homocysteine was not independently associated with the presence of VFs, which was mainly related to the osteoporotic status. Although a weak association was observed between hyperhomocysteinemia and low BMD and a trend to higher prevalence of grade 2/3 VFs was observed, our study did not confirm that homocysteine, vitamin B(12), and folate status are important determinants of prevalent asymptomatic VFs in postmenopausal women. PMID- 22321655 TI - Insulin resistance in type 2 diabetes mellitus may be related to bone mineral density. AB - The mechanism of bone mineral density (BMD) changes in type 2 diabetes mellitus is not clear. We aimed to investigate the effect of insulin resistance in type 2 diabetics on BMD. Insulin resistance was determined using the homeostasis model assessment index (HOMA-IR). Nineteen type 2 diabetic patients with a HOMA-IR <2.7 (mean age, 51.5+/-9.6yr; body mass index [BMI], 27.3+/-5.1kg/m(2); duration of diabetes, 10.5+/-7.3yr) were included in Group A, and 30 BMI- and age-matched type 2 diabetic patients with a HOMA-IR >=2.7 were included in Group B. The BMD was measured with dual-energy X-ray absorptiometry. Independent t-test was used for statistical analysis. The Group A values for mean fasting glucose and insulin levels were 160.1+/-77.0mg/dL and 4.79+/-2.89MUU/L, respectively, whereas the Group B values were 195.1+/-58.9mg/dL (p>0.05) and 19.30+/-16.89MUU/L (p=0.0001). Significantly higher total lumbar vertebra T-score (p=0.02) and total lumbar vertebra BMD in Group A were determined than Group B (p=0.033). The lumbar vertebra total Z-score was significantly lower in Group B (p=0.042). Marked insulin resistance may have a negative effect on BMD in type 2 diabetics, while the presence of hyperinsulinemia may be associated with the low BMD. PMID- 22321656 TI - Social determinants of bone densitometry uptake for osteoporosis risk in patients aged 50yr and older: a systematic review. AB - The World Health Organization identifies that osteoporosis is one of the leading health problems in the Western world. An increased risk of fragility fracture is observed in more socially disadvantaged individuals in most Western countries. Dual-energy X-ray absorptiometry (DXA) is currently the procedure of choice to diagnose osteoporosis and assess fracture risk. We systematically reviewed the literature regarding social determinants of DXA utilization for osteoporosis detection in patients aged 50yr and older using a computer-aided search of MEDLINE, EMBASE, CINAHL, and PsychINFO from January 1994 to December 2010. Five cross-sectional studies, incorporating 16 separate analyses, were identified for inclusion in this review. The best evidence analysis identified limited evidence for a positive association between either income or education with DXA utilization; furthermore, the best evidence analysis found no evidence for an association between either marital status or working status and DXA utilization. Further research is required to identify whether a relationship exists and elucidate reasons for disparities in DXA utilization between different social groups, such as choice and referral processes, as a necessary precursor in identifying modifiable determinants and appropriate strategies to promote preventive screening to identify fracture risk. PMID- 22321657 TI - The prevalence of low bone mineral density in Brazilian patients with systemic lupus erythematosus and its relationship with the disease damage index and other associated factors. AB - The aim of this study was to examine the prevalence of osteoporosis, osteopenia, and bone mineral density (BMD) less than the expected range based on age in patients with systemic lupus erythematosus (SLE) in a tropical region of Brazil and the relationship between reduced BMD and several associated factors, especially the SLE disease damage index (SDI). We scored 159 patients with creatinine clearance of 60 mL/min or more for SDI, which was modified by excluding the osteoporosis item. For postmenopausal women and men older than 50 yr, T-scores identified osteopenia (<-1.0 and >-2.5) and osteoporosis (<=-2.5). For all patients, a Z-score of -2.0 or less identified BMD less than the expected range for age. Other variables that influence BMD were studied. The prevalence of osteoporosis, osteopenia, and BMD less than the expected range for age was 28%, 54%, and 29.6%, respectively. The Z-scores were significantly lower in patients with a modified SDI >= 1 (mean +/- standard deviation [SD]=-1.45 +/- 1.18) compared with patients with a modified SDI=0 (mean +/- SD=-0.94 +/- 1.01; p=0.01). The lowest Z-score had a significant association with postmenopausal status (p=0.038) and significant correlations with the duration of glucocorticoid (GC) usage (p=0.033, r=-0.17), the cumulative amount of GC (p=0.000, r=-0.28), and parathyroid hormone levels (p=0.003, r=-0.24). A multiple linear regression revealed that the modified SDI (p=0.003) and the cumulative amount of GC (p=0.006) had significant independent associations with the lowest Z-score. In conclusion, a BMD less than the expected range for age occurs frequently in Brazilian patients with SLE independent of the renal failure. The patients with greater SDIs had lower Z-scores, which suggests a direct association between chronic inflammation from disease and a reduced BMD. PMID- 22321658 TI - Dual-energy X-ray absorptiometry in the evaluation of abdominal aortic calcifications. AB - The objective of this study was to evaluate the diagnostic performance of the new dual-energy X-ray absorptiometry equipment vs digital radiography (DR) in the detection and scoring of abdominal aortic calcifications (AACs). Seventy-five patients with indication for morphometric evaluation of the spine underwent vertebral fracture assessment (VFA) and spinal DR (gold standard). The radiographic and VFA images were analyzed to detect AAC using a previously validated 24-point scale (AAC-24) and a simplified 8-point scale (AAC-8). The evaluation was conducted by 2 expert radiologists and repeated by the more experienced of the 2 after 7d to verify the results. Patients with a score of 5 or more in AAC-24 and 3 or more in AAC-8 were considered at risk for cardiovascular diseases (CVDs). The aorta was not completely visible in 11 VFA and 1 DR images. DR detected AAC in 42 of the 63 patients (66.7%), whereas 15 patients (23.8%) were considered at risk for CVD. The VFA showed sensitivity, specificity, and accuracy in the detection of AAC with values of 78.6%, 85.7%, and 81.0%, respectively, with both AAC-24 and AAC-8; in the identification of patients at risk for CVD, VFA demonstrated sensitivity, specificity, and accuracy, respectively, with values of 86.7%, 100%, and 96.8% using AAC-24 and 86.7%, 93.8%, and 92.1% using AAC-8. In the detection of AAC, intraobserver agreement was superimposable using both the techniques (kappa=1.00), whereas in the identification of patients at risk for CVD, kappa values were 0.96 and 0.95 using AAC-24 and 1.00 and 0.96 using AAC-8 for DR and VFA, respectively. Interobserver agreement in the evaluation of the presence/absence of AAC showed a kappa value of 0.76 for DR and 0.71 for VFA, whereas kappa values of 0.91 and 0.87 for DR and 0.85 and 0.83 for VFA were achieved for CVD risk using AAC-24 and AAC-8, respectively. AAC can be easily and accurately diagnosed by VFA with satisfactory accuracy, reproducibility, and repeatability. VFA may be used in the assessment and monitoring of AAC. PMID- 22321659 TI - Commentary on calcium supplements and cardiovascular events. PMID- 22321660 TI - Clinical observations in total body DXA: technical aspects of positioning and analysis. AB - Total body (TB) dual-energy X-ray absorptiometry (DXA) can assess regional body composition, which may necessitate greater attention to patient positioning and analysis than required for whole body assessment. This report describes technical challenges experienced in performing TB DXA, explores the frequency with which autoanalysis inaccuracies occur, assesses their effect on regional body composition results, and describes a uniform clinical approach for TB DXA positioning and analysis. Patient positioning followed manufacturer recommendations with additional facility-imposed procedures. On visual inspection, it was apparent that automated analysis often did not meet manufacturer guidelines, thus requiring manual alteration. To explore the frequency with which manual adjustments were needed, and the impact on results, TB scans were obtained in 20 men and 20 women aged 18-93 yr. The head line was altered in 98%, one or both shoulder lines in 93%, and the lateral hip boundary in 40%. Manual and automated TB analyses were highly correlated (r(2)=0.98-1.00). However, regional result correlation was less robust, that is, automated and manual appendicular lean mass differed by more than our least significant change in 33%. In conclusion, manual correction of automated TB DXA scan analysis is often needed. Such alterations do not affect TB measures but may affect regional body composition results. PMID- 22321661 TI - Hip cortical thickness assessment in postmenopausal women with osteoporosis and strontium ranelate effect on hip geometry. AB - The aims of this study were to assess the relationship between hip geometry and the 5-yr risk of hip fractures in postmenopausal osteoporotic women and the effects of strontium ranelate on these parameters. Using the 5-yr data of a randomized placebo-controlled trial of strontium ranelate (Treatment of Peripheral Osteoporosis Study [TROPOS]), we reanalyzed the hip dual-energy X-ray absorptiometry scans to determine the role of hip geometry in the risk of hip fractures (placebo group, n=636) and to analyze the effects of strontium ranelate (n=483). The outcomes included the hip structure analysis (HSA) parameters: cross sectional area (CSA), section modulus, cortical thickness, and buckling ratio, measured at femoral neck, intertrochanteric (IT) region, and proximal shaft. The geometric parameters associated with an increased risk of hip fracture over 5yr were IT CSA and femoral shaft cortical thickness independent of age and total-hip bone mineral density (BMD). Using Bonferroni adjustment, IT cortical thickness was associated with the risk of hip fracture. Over 5yr, significant decreases in some femoral dimensions of the placebo group contrast with significant increases in strontium ranelate group after adjustment for age and BMD. Using Bonferroni adjustment, differences between placebo and strontium ranelate groups were no longer significant after adjustment on 5-yr BMD changes. Some HSA parameters have predictive value for hip fracture risk in postmenopausal osteoporotic women. Strontium ranelate improves some HSA parameters, through the BMD increase. PMID- 22321662 TI - A senescent cell bystander effect: senescence-induced senescence. AB - Senescent cells produce and secrete various bioactive molecules including interleukins, growth factors, matrix-degrading enzymes and reactive oxygen species (ROS). Thus, it has been proposed that senescent cells can damage their local environment, and a stimulatory effect on tumour cell growth and invasiveness has been documented. However, it was unknown what effect, if any, senescent cells have on their normal, proliferation-competent counterparts. We show here that senescent cells induce a DNA damage response, characteristic for senescence, in neighbouring cells via gap junction-mediated cell-cell contact and processes involving ROS. Continuous exposure to senescent cells induced cell senescence in intact bystander fibroblasts. Hepatocytes bearing senescence markers clustered together in mice livers. Thus, senescent cells can induce a bystander effect, spreading senescence towards their neighbours in vitro and, possibly, in vivo. PMID- 22321663 TI - Total or partial inferior border ostectomy for mandibular contouring: indications and outcomes. AB - Among the East Asian population, a long or square face produces a characteristic coarse and masculine appearance and is therefore considered undesirable and unattractive. Because of this many Orientals seek to achieve a harmonious contour of their face by undergoing various cosmetic surgical procedures. Mandibular contouring for a long or asymmetrical face with/without square jaw is rarely reported in the literature and the objective of this study was to investigate the effectiveness of total or partial inferior border ostectomy for mandibular contouring and to discuss its indications. From July 2005 to November 2009, 74 patients in this study received mandibular contouring by total or partial inferior border ostectomy procedure to correct a disharmonious facial contour. Postoperatively the appearance of all 74 cases showed that the length of the lower 3rd of the face and the width of the mandible were decreased effectively, and the mandibular contour was improved. The final aesthetic outcomes were satisfactory for both the surgeons and the patients. The results suggest that facial contour could be improved by using total or partial inferior border ostectomy of the mandible thus achieving a harmonious facial outline based on East Asian aesthetics. PMID- 22321664 TI - Evaluation of cost-effectiveness of live oral pentavalent reassortant rotavirus vaccine introduction in Ghana. AB - BACKGROUND: Globally, rotavirus gastroenteritis is the most common identifiable cause of severe diarrhea in children under 5. Recently introduced rotavirus vaccines from Merck & Co. and GlaxoSmithKline have the potential to save hundreds of thousands of lives. Efficacy results in Ghana suggest Merck & Co.'s live oral pentavalent rotavirus vaccine (RotaTeq((r))) prevents 65.0% of severe gastroenteritis due to rotavirus infection in children under 5. The announcement by Merck and GSK to make their rotavirus vaccines available for developing nations at reduced prices provides Ghana with the opportunity to introduce rotavirus vaccines into the national immunization program after investigation of the medical, economic and political implications. METHODS: We estimated the average costs of treating children with diarrhea in the Ashanti region of Ghana as inpatients and outpatients. Using these results, data from rotavirus surveillance studies, and recent rotavirus vaccine efficacy evaluation, we estimated the cost-effectiveness of introducing RotaTeq in Ghana. RESULTS: Based on our prospective calculations, we estimated an average inpatient and outpatient costs of $233.97 and $17.09, respectively, for treating childhood diarrhea. Using the 2003 birth cohort, RotaTeq introduction could save 1554 lives and avert 93,109 disability-adjusted life-years (DALYs) annually. At a market price of $5 per dose, introducing RotaTeq would have a base-case cost of $62.26 per DALY averted, at a market price of $3.50 per dose, a base-case cost of $39.59 per DALY averted and at market cost of $1 per dose, a base-case cost of $1.81 per DALY averted. All three values are below the 2009 Ghana per capita GDP. Thus, RotaTeq introduction into Ghana will be very cost-effective. Sensitivity analyses suggest these results are robust. CONCLUSIONS: RotaTeq vaccination for children under five in Ghana would be a highly cost-effective public health intervention. Ghanaian health officials should seek GAVI funding and evaluate how to maximize RotaTeq access. PMID- 22321666 TI - [Atlantoaxial rotary subluxation]. PMID- 22321665 TI - Changes in IL-10 and specific antibodies associated to successful Dermatophagoides pteronyssinus immunotherapy in children during the first year of treatment. AB - BACKGROUND: Allergen-specific immunotherapy (SIT) is a long-term treatment of respiratory allergy. OBJECTIVE: To look for early predictors of the effectiveness of Dermatophagoides pteronyssinus SIT. METHODS: A prospective multi-centre study was carried out in Spain. Children with D. pteronyssinus rhinitis or asthma were invited to participate. The study was divided into times: T0 (recruitment); T1 (inclusion); T2 a-f (immunotherapy times) and T3 (the end of study). Efficacy of SIT was assessed by clinical scores, visual analogue scales (VAS) and lung function tests. We performed D. pteronyssinus skin tests at T1 and T3, and determined specific serum IgE, IgG4 and IL-10 at T1, T2f and T3. Data were analysed using Mann-Whitney and Kruskal-Wallis tests, compared using Wilcoxon and Chi-square tests, and correlated to Spearman test. All tests had a significance level of 0.05. RESULTS: Thirty-eight children completed the study. At T1 all had rhinitis and 34 also had asthma. At T3, 30 patients had improved, six experienced no changes and two worsened. Improvement was associated to FEV1/FVC and VAS improvement; to a reduction in D. pteronyssinus skin prick test; to a progressive increase in serum levels of D. pteronyssinus IgE, and D. pteronyssinus, Der p1 and Der p2 IgG4. IL-10 levels showed an early increase at T2f (the end of initial build-up immunotherapy phase), and then a reduction at T3 (the end of a year of immunotherapy). Improvement associated to an early increase in IL-10 and was correlated with VAS and specific IgG4 evolution. PMID- 22321667 TI - Differentiating first episode substance induced and primary psychotic disorders with concurrent substance use in young people. AB - OBJECTIVE: Substance use is common in first-episode psychosis, and complicates the accurate diagnosis and treatment of the disorder. The differentiation of substance-induced psychotic disorders (SIPD) from primary psychotic disorders (PPD) is particularly challenging. This cross-sectional study compares the clinical, substance use and functional characteristics of substance using first episode psychosis patients diagnosed with a SIPD and PPD. METHOD: Participants were 61 young people (15-24 years) admitted to a psychiatric inpatient service with first episode psychosis, reporting substance use in the past month. Diagnosis was determined using the Psychiatric Research Interview for DSM-IV Substance and Mental disorders (PRISM-IV). Measures of clinical (severity of psychotic symptoms, level of insight, history of trauma), substance use (frequency/quantity, severity) and social and occupational functioning were also administered. RESULTS: The PRISM-IV differentially diagnosed 56% of first episode patients with a SIPD and 44% with a PPD. Those with a SIPD had higher rates of substance use and disorders, higher levels of insight, were more likely to have a forensic and trauma history and had more severe hostility and anxious symptoms than those with a PPD. Logistic regression analysis indicated a family history of psychosis, trauma history and current cannabis dependence were the strongest predictors of a SIPD. Almost 80% of diagnostic predictions of a SIPD were accurate using this model. CONCLUSIONS: This clinical profile of SIPD could help to facilitate the accurate diagnosis and treatment of SIPD versus PPD in young people with first episode psychosis admitted to an inpatient psychiatric service. PMID- 22321668 TI - Self-reported empathy deficits are uniquely associated with poor functioning in schizophrenia. AB - BACKGROUND: Social cognitive deficits have been proposed to be among the causes of poor functional outcome in schizophrenia. Empathy, or sharing and understanding the unique emotions and experiences of other people, is one of the key elements of social cognition, and prior studies suggest that empathic processes are impaired in schizophrenia. The current study examined whether impairments in self-reported empathy were associated with poor functioning, above and beyond the influences of neurocognitive deficits and psychopathology. METHODS: Individuals with schizophrenia (n=46) and healthy controls (n=37) completed the Interpersonal Reactivity Index (IRI), a measure of emotional and cognitive empathy. Participants also completed a neuropsychological test battery, clinical ratings of psychopathology, and functional outcome measures assessing both functional capacity and community functioning. After testing for between group differences, we assessed the relationships between self-reported empathy and the measures of functioning, neurocognition, and psychopathology. Regression analyses examined whether empathic variables predicted functional outcomes. RESULTS: Individuals with schizophrenia reported lower IRI scores for perspective taking and empathic concern, and higher IRI scores for personal distress than controls. Among individuals with schizophrenia, lower perspective-taking, greater disorganized symptoms, and deficits in working memory and episodic memory were correlated with poorer functional capacity and community functioning. Lower scores for perspective-taking explained significant incremental variance in both functional capacity (DeltaR(2)=.09, p<.05) and community functioning (DeltaR(2)=.152, p<.01) after accounting for relevant neurocognitive and psychopathological variables. CONCLUSIONS: Impaired perspective-taking, a component of cognitive empathy, is associated with poor functioning even after taking into account the influences of neurocognitive deficits and psychopathology. These findings support further efforts to clarify the underlying causes of empathic disturbances and suggest that treatments for these disturbances may help functional recovery in schizophrenia. PMID- 22321669 TI - Evaluation of the Indian Migration Study Physical Activity Questionnaire (IMS PAQ): a cross-sectional study. AB - BACKGROUND: Socio-cultural differences for country-specific activities are rarely addressed in physical activity questionnaires. We examined the reliability and validity of the Indian Migration Study Physical Activity Questionnaire (IMS-PAQ) in urban and rural groups in India. METHODS: A sub-sample of IMS participants (n = 479) was used to examine short term (<= 1 month [n = 158]) and long term (> 1 month [n = 321]) IMS-PAQ reliability for levels of total, sedentary, light and moderate/vigorous activity (MVPA) intensity using intraclass correlation (ICC) and kappa coefficients (k). Criterion validity (n = 157) was examined by comparing the IMS-PAQ to a uniaxial accelerometer (ACC) worn >= 4 days, via Spearman's rank correlations (rho) and k, using Bland-Altman plots to check for systematic bias. Construct validity (n = 7,000) was established using linear regression, comparing IMS-PAQ against theoretical constructs associated with physical activity (PA): BMI [kg/m2], percent body fat and pulse rate. RESULTS: IMS-PAQ reliability ranged from ICC 0.42-0.88 and k = 0.37-0.61 (<= 1 month) and ICC 0.26 to 0.62; kappa 0.17 to 0.45 (> 1 month). Criterion validity was rho = 0.18-0.48; k = 0.08-0.34. Light activity was underestimated and MVPA consistently and substantially overestimated for the IMS-PAQ vs. the accelerometer. Criterion validity was moderate for total activity and MVPA. Reliability and validity were comparable for urban and rural participants but lower in women than men. Increasing time spent in total activity or MVPA, and decreasing time in sedentary activity were associated with decreasing BMI, percent body fat and pulse rate, thereby demonstrating construct validity. CONCLUSION: IMS-PAQ reliability and validity is similar to comparable self-reported instruments. It is an appropriate tool for ranking PA of individuals in India. Some refinements may be required for sedentary populations and women in India. PMID- 22321670 TI - The International Myeloma Society comes of age. PMID- 22321671 TI - [The process of abdominal aortic aneurysm treatment]. PMID- 22321672 TI - [Correct assessment, scientific selection, rational therapy. To do the right choice on the treatment of abdominal aortic aneurysm]. PMID- 22321673 TI - [Comparison of open and endovascular repair for abdominal aortic aneurysm mid term outcomes: a single center randomized controlled trial]. AB - OBJECTIVE: To compare the effects of open and endovascular repair for abdominal aortic aneurysm. METHODS: Between January 2009 and January 2011, 84 patients were randomized to endovascular aneurysm repair (EVAR) or open repair. There were 48 patients in EVAR group, 42 cases were male (87.5%), 6 cases were female (12.5%), aged from 50 to 83 years with a mean of 70.8 years. There were 36 patients in open repair group, 31 cases were male (86.1%), 5 cases were female (13.9%), aged from 50 to 80 years with a meal of 67.4 years. The results of perioperative period and follow-up were analyzed. RESULTS: Between the two groups, there was significant difference on operative time (t = 9.863, P = 0.000), blood loss (t = 4.647, P = 0.000), blood transfusion (t = 3.334, P = 0.002), hospital stay (t = 2.327, P = 0.022), and medical expense (t = 2.314, P = 0.023). There was no significant difference for perioperative complications (chi(2) = 0.480, P = 0.488). There was no significant difference for complications (chi(2) = 0.664, P = 0.415) and mortality (P = 0.429) during 3 months follow-up. There was no significant difference for complications during 6 months follow-up (chi(2) = 0.128, P = 0.720). CONCLUSIONS: Operative time, blood loss and transfusion, hospital stay in EVAR group are less than which in open repair group, the medical expense of EVAR was higher than open repair. There is no significant difference for complications during 6 months follow-up between 2 groups. Long-term follow-up and more patents are needed to analyze survival rate and long-term complications. PMID- 22321674 TI - [Endovascular aneurysm repair in high-surgical-risk abdominal aortic aneurysm patients: initial and long-term results]. AB - OBJECTIVE: To evaluate the initial and long-term results of endovascular aneurysm repair (EVAR) in high-surgical-risk abdominal aortic aneurysm (AAA) patients. METHODS: From July 1997 to July 2011, 120 consecutive high-surgical-risk patients with AAA who were treated electively using a bifurcated aortic endograft were entered in a registry. There were 96 male and 24 female patients, aged from 52 to 95 years with a mean of 74 years. Follow-up protocol consisted of computed tomography angiograms or ultrasound performed at 3, 6, 9, 12 months, and annually thereafter. The main goal was evaluation of the operative mortality and the long term survival of these patients. Secondary goals were determination of the frequency of secondary operations, the outcome of the aneurysm sac, and primary and secondary patency rates after aortic endograft placement. RESULTS: Mean aneurysm diameter was (57 +/- 8) mm. Thirty-seven patients were operated under local anesthesia and eighty-three under general anesthesia. Five type I endoleaks, twenty-five type II endoleaks and one type III endoleak occurred during the perioperative period. The technical success rate was 95%. Operative mortality was 2.5%. The survival rates at 1-, 3- and 5-year were 92%, 75% and 43% respectively. The mean follow up was (36 +/- 3) months. Primary and secondary patency rates at 3 year were respectively 97% and 100%. Secondary intervention rate was 10% (12/120) at 5 year. The reasons included endoleaks for 7 patients, stent-grafts fracture for 2 patients, stent-grafts migration for 2 patients and stent-graft thrombosis for 1 patients. CONCLUSIONS: Initial and long-term results with endograft repair of AAA in high-surgical-risk patients were satisfactory. These results appear to justify endovascular repair for this patient population. PMID- 22321675 TI - [Investigation of endovascular aneurysm repair of complex abdominal aortic aneurysm in high-risk patients]. AB - OBJECTIVE: To evaluate the results of a variety of alternative endovascular techniques applied to patients with complicated abdominal aortic aneurysm complex abdominal aortic aneurysm (cAAA) and unsuitable for open surgery. METHODS: From January 2001 to December 2010, charts of all patients having an abdominal aortic aneurysm (AAA) were reviewed. Endovascular aneurysm repair (EVAR) was done in 138 patients, in which 9 patients were defined as cAAA such as juxta-renal AAA, short or angulated AAA neck, AAA with bilateral iliac artery aneurysms. There were 8 male and 1 female patients, aged from 26 to 87 years with a mean of 67 years. All these patients at high risk for open surgery were offered a modified EVAR technique including fenestrated technique, scallop technique, chimney technique, balloon assisted U-turn stenting and reverse-U stent-graft in 2, 5, 1 and 1 patients respectively. RESULTS: All techniques were successful and without severe postoperative complications. An intraoperative endoleak was found in 4 patients and was corrected immediately. One patient with type I and III endoleaks underwent dilatation with a compliant balloon. Two patients with type I endoleak underwent coil embolization (1 patient) and bare stent (1 patient). During follow up, one patient with a type II endoleak who demonstrated no increase in sac diameter during follow-up was observed. Mean follow-up was 25.9 months (ranging from 4 to 79 months). No rupture occurred and 8 aneurysms shrink significantly. In 7 patients, critical vessels (renal and mesenteric arteries) were protected during the initial procedure and remained patent except in one patient who was performed reverse "U" stent graft with thrombosis in hypogastric artery. CONCLUSION: High-risk patients with cAAA inappropriate for traditional EVAR can be successfully treated by using simple ancillary endovascular techniques with acceptable short or mid-term results. PMID- 22321676 TI - [Fibrin glue embolization treating intra-operative type I endoleak of endovascular repair of abdominal aortic aneurysm: long-term result]. AB - OBJECTIVES: To analyze the long-term results of fibrin glue embolization to eliminate type I endoleaks after endovascular aneurysm repair (EVAR), and to assess the feasibility and durability of this technique. METHODS: From August 2002 to June 2010, among the 953 EVAR patients, 51 (5.4%) patients underwent intraoperative transcatheter fibrin glue sac embolization to resolve type I endoleak persisting after initial intraoperative maneuvers to close the leak or in necks too short or angulated for cuff placement. Computed tomographic angiography was performed to assess the outcome after 3, 6, and 12 months and annually thereafter. A retrospective study was conducted, and characteristics of the patients, intra-sac pressure, hospital course, and long-term outcomes were recorded. RESULTS: Among the 51 patients, 19 (37.3%) patients had proximal necks long < 10 mm, and 6 (11.8%) patients had proximal neck angulation > 60 degrees ; 22 patients (3 additional iliac extension, 14 cuffs, and/or 8 stents) had been placed with additional devices. After fibrin glue injection, 50 (98.0%) of the 51 endoleaks were successfully resolved, and intra-sac pressure (including systolic, diastolic, mean pressures, pulse pressure, and the mean pressure indexes) decreased significantly in these cases. The patient who failed embolotherapy was converted to open surgery (2.0%); he died 2 months later from multiorgan failure. And other two (4.8%) patients died in the peri-operative period from myocardial infarction. The median of follow-up of 48 patients was 45 months (range 4 - 106 months). The mean maximal aneurysm diameter fell from the baseline (61.5 +/- 15.2) mm to (48.8 +/- 10.1) mm (P = 0.000). Three (6.2%) patients died in the follow-up duration (1 aneurysm-related, died of renal failure which was caused by the compromised renal artery). Cumulative survival was 97.9% at 1 year, 94.5% at 3 years, and 90.8% at 4 years. No recurrent type I endoleak or glue-related complications were observed in follow-up. CONCLUSIONS: Fibrin glue embolization to eliminate type I endoleak after EVAR has yielded promising results in this study, and it can effectively and durable resolve the type I endoleaks. Balloon occlusion of the inflow of the endoleak must be done during glue injection, to enhance the safety and facilitate formation of a structured fibrin clot. PMID- 22321677 TI - [Complications in endovascular repair of abdominal aortic aneurysms: treatment and prevention]. AB - OBJECTIVE: To review the prevention and treatment strategies in the complications after endovascular repair (EVAR) of abdominal aortic aneurysms, retrospectively in a single medical center. METHODS: From January 2003 to December 2010, clinical data of 344 EVAR cases were analyzed retrospectively, including postoperative period and long-term results. There were 302 male and 42 female patients, with a mean age of (69 +/- 8) years. Patients were followed up at 3 months, 6 months, and then every year with abdominal x-ray and spiral CT angiography. RESULTS: The surgical success rate was 99.7% (343/344). The mortality with elective and emergency surgery was 0.30% (1/334) and 1/10 respectively. The average follow-up time was 3 to 84 months with a mean of 32.9 months. The follow-up rate was 81.8% (279/341). The mortality was 1.1% (3/279), the re-intervention rate was 10.4% (29/279) and the overall complication rate was 12.9% (36/279), including endoleak 5.7% (16/279), stent-graft migration 1.1% (3/279), aneurysm expansion or rupture 5.4% (15/279), limb occlusion 2.5% (7/279) and stent-graft infection 1.4% (4/279). CONCLUSION: EVAR has allowed a minimally invasive approach to aortic pathology. A careful preoperative assessment is the key for EVAR. Endoleak continues to be the major long-term complication of the endoluminal grafting technique, and the major cause for re-intervention. Life-long follow-up is an integral part of EVAR. PMID- 22321678 TI - [Endovascular repair of abdominal aortic aneurysm: a clinical report of 81 cases]. AB - OBJECTIVE: To evaluate the efficacy and safety of endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA), and to compare the prognosis between patients of different ages. METHODS: The hospitalization and follow-up data of 81 AAA patients treated by EVAR from May 2005 to May 2011 were retrospectively analyzed. All the patients were divided into advanced age group (age >= 75 years, 24 cases) and relatively young group (age < 75 years, 57 cases). General conditions, comorbidity, procedure, in-hospital complications, and follow-up were compared between these two groups. RESULTS: All covered stents were successfully deployed, a technical success rate of 91.4% (74/81) was achieved. There was no intraoperative death. In-hospital mortality was 1.2% (1/81). The follow-up rate was 91.4% (74/81), with a mean follow-up of 47.5 months. Twelve deaths were recorded during follow-up, 1, 2, 3, 4, and 5-year survival rates were 98.6%, 92.2%, 80.8%, 58.7%, and 44.1%, respectively. When compared with relatively young group, the advanced age group had a lower rate of abdominal pain as the major symptom, but a higher rates of renal diseases and coronary artery diseases. Furthermore, the advanced age group had a longer stay in intensive care unit and higher morbidity of endoleaks, and also tended to have increased rates of pulmonary infection and access site hematoma, while the other parameters were similar between the two groups. CONCLUSIONS: EVAR of AAA is less invasive, safe, and effective during short to mid-tern follow-up. The patients of advanced age suffer from higher rates of some complications, thus careful perioperative preparation and intensive monitor are mandatory for preventing or treating potential complications and improving prognosis for these patients. PMID- 22321679 TI - [Endovascular repair of descending aortic pseudoaneurysms]. AB - OBJECTIVE: To evaluated the feasibility, efficacy, and outcome of endovascular repair for descending aortic pseudoaneurysms. METHODS: From April 2007 to November 2010, 20 patients of descending aortic pseudoaneurysm were treated. There were 18 male and 2 female, aged from 28 to 82 years with a mean of (58 +/- 16) years. In this group, 4 patients were diagnosed as Behcet's syndrome, 6 patients as mycotic pseudoaneurysms with positive blood culture, 6 patients as suspected mycotic pseudoaneurysms, 1 patient with iatrogenic pseudoaneurysm and 1 patient with chronic grain-mononuclear cell leukemia, the other 3 patients with unknown reasons. The 88.5% of aortic pseudoaneurysms were located at abdominal aorta. Fifteen patients underwent endovascular therapy and 2 patients were treated by traditional open surgery. The other 3 patients underwent conservative treatments. The data of treatments and follow-up in the 15 patients who received endovascular repairs were retrospectively analyzed. RESULTS: Endovascular therapy was performed successfully on the 15 patients, and the technique successful rate was 15/15. Total 15 stents were transluminal placed including 6 bifurcate stent grafts, 6 abdominal straight stent-grafts, 2 thoracic straight stent-grafts and 1 abdominal bare stent. One patient was treated by stent assisted embolization. Perioperative mortality rate was 0. Only 2 primary type IV endoleaks were found. Fourteen patients were successfully followed up. During a mean follow-up of 538 days, 8 (57.1%) patients were uneventful. Six (42.9%) patients were complicated by aneurysm related events, including 4 (28.6%) aneurysm-related deaths, 1 (7.14%) with delayed endoleak and 1 (7.14%) with recurrent pseudoaneurysm which was retreated by another stent-graft. CONCLUSIONS: Endovascular therapy for descending aortic pseudoaneurysms is a feasible and mini-invasive option with high technique success rate and low perioperative mortality rate. However, risk of recurrence and rupture to death of pseudoaneurysm remains high during follow up. Treating the underlying reasons and intensively follow-up may be good for improving the prognosis of descending aortic pseudoaneurysms treated by endovascular therapy. PMID- 22321680 TI - [Endovascular repair of infrarenal abdominal aortic aneurysm with the complex aortic anatomy]. AB - OBJECTIVE: To explore the safety and efficiency of endovascular repair (EVAR) of abdominal aortic aneurysms (AAAs) which have the complex aortic anatomy. METHODS: The clinical date of 48 AAA patients with complex aortic anatomy treated by EVAR from January 2003 to March 2011 was retrospectively analyzed. There were 37 male and 11 female patients, aged from 50 to 81 years with a mean of 71.4 years. Fourteen patients had short aortic neck (< 15 mm), 13 patients had severe infrarenal angulation (> 60 degrees ), 15 patients had severely tortuous iliac, 6 patients had small iliac (< 8 mm). The stent-grafts were deployed by both femoral arteries to treat the AAA. RESULT: The primary technical success rate was 100%. The perioperative survival rate was 100%. Intraoperative angiograms revealed two type I endoleaks, in which one disappeared in two weeks, another existed. Follow up was available in 40 patients with a median of 63 months (4 to 122 months). During the follow-up period, 2 patients died with no relationship to the procedures. The rest patients survived well. The accumulative survival rate was 95.8%. There were no new endoleak, stent-graft migration, aneurysm expansion, or secondary intervention during the follow-up time. CONCLUSIONS: EVAR is safety and efficiency to treat the patient of infrarenal abdominal aortic aneurysm with the complex aortic anatomy. By the accumulation of experience, EVAR will play a more important role for these patients. PMID- 22321681 TI - [The treatment strategy of special distal landing zones in endovascular repair of abdominal aortic aneurysm]. AB - OBJECTIVE: To study the assessment and management for abdominal aortic aneurysm (AAA)'s special distal landing zones in endovascular repair (EVAR). METHODS: The clinic data of 66 AAA patients with complicated distal landing zones From January 2007 to December 2010 was retrospectively analyzed. There were 45 male and 21 female patients, aged from 53 to 87 years with a mean of 62 years. All patients underwent the CT angiography examination (1 to 2 mm interval) to obtain the necessary anatomical data. In this group, there were 20 cases with type I and IIA lesions, including 10 cases with narrow common iliac arteries/external iliac arteries (> 50%), 6 cases with seriously distorted common iliac arteries/external iliac arteries, 4 cases with the characters of the above, 16 cases with bilateral common iliac aneurysms, 46 cases with bilateral common iliac aneurysms combined internal iliac aneurysms (unilateral 32 cases, bilateral 14 cases). The vascular stent-grafts' usage was as follow: Metronic 46 cases, COOK 14 cases, Microport 4 cases, Lifetech 2 cases. RESULTS: The mean operative time was 90 min. There were significant stent-graft shortening in 22 cases (33.3%), type II endoleak in 18 cases (27.3%), type III endoleak in 5 cases (7.6%), iliac stents' stenosis (> 50%) in 2 cases (3.0%), type II combined with type III endoleak in 5 cases (7.6%), iliac stents' stenosis combined with type III endoleak in 4 cases (6.1%). Patients were followed for a mean of 22 months (range from 3 to 36 months), during the time of follow-up, the following conditions were observed: stent-graft displacement (to the remote < 10 mm) in 2 cases (3.0%), iliac stents restenosis (> 50%) 2 cases, type II endoleak healed in 18 cases (18/23, 78.3%), and no type III endoleak remained. The fatality rate was 3.0% (2/66). CONCLUSIONS: Special distal landing zones increased the operative complication rate in EVAR. Being familiar with the features of stent-graft and appropriate use of various surgical management can increase the success ratio of EVAR. PMID- 22321682 TI - [Inguinal hernia repair with acellular tissue matrix patch for pediatric patients aged 6 to 18 years]. AB - OBJECTIVE: To evaluate the safety and efficacy of hernioplasty using acellular tissue matrix patch to repair inguinal hernia of pediatric patients aged 6 to 18 years. METHODS: Sixty eligible patients aged 6 to 18 years with primary unilateral inguinal hernia were randomly assigned to experimental or control group from June to December 2009. In the experimental group, acellular tissue matrix patch was used during Lichtenstein herniorrhaphy while traditional high ligation of hernial sac was used in the control group. Preoperative and postoperative parameters such as clinical informations of patients, postoperative complications and recurrence rate were recorded and analyzed. RESULTS: There were no significant differences between the 2 groups in postoperative length of stay [(31 +/- 8) h vs. (34 +/- 11) h] and postoperative Visual Analogue Scale Pain Score (2.8 +/- 0.9 vs. 2.6 +/- 1.0) (P > 0.05), but the operation time in the experimental group were longer than that in the control group significantly [(39 +/- 4) min vs. (36 +/- 4) min, t = 3.357, P = 0.001]. The duration of follow-up ranged from 14 to 20 months. There were no postoperative incisional infection, chronic postoperative pain and local foreign body sensation in two groups. In the experimental group, 3 patients suffered scrotal hydrocele as compared 2 patients in the control group. There was no recurrence in the experimental group as compared 2 patients (6.7%) in the control group, which was no significant difference (P > 0.05). CONCLUSION: Lichtenstein repair for pediatric patients aged 6 to 18 years with acellular tissue matrix patch has good results and with limited postoperative complications. PMID- 22321683 TI - [The clinical study of high-frequency ultrasound-guided vacuum-assisted biopsy for breast microcalcifications]. AB - OBJECTIVE: To evaluate the clinical application of high-frequency ultrasound guided vacuum-assisted biopsy for breast microcalcifications. METHODS: Sixty-six patients with 70 lesions of microcalcifications detected at mammography underwent high-frequency ultrasound-guided vacuum-assisted biopsy from July 2009 to October 2010. All patients were female, aged 24 to 61 years (median age 40 years). Among 70 lesions of microcalcifications, unilateral lesions were 62 cases and bilateral lesions were 4 cases. The clinical factors that affected the success of biopsy were investigated by chi(2) test and Logistic regression analysis. RESULTS: Among 70 lesions of microcalcifications, the successful rate of biopsy was 72.9% (51/70). The biopsy successful rate of microcalcifications without and with masses were 65.2% (30/46) and 87.5% (21/34) respectively (chi(2) = 3.960, P = 0.047). The biopsy successful rate of microcalcifications of maximal diameter more than 5 mm was higher than that of maximal diameter less than 5 mm (88.9% vs. 55.9%, chi(2) = 9.633, P = 0.002). The Logistic regression analysis showed that the types and maximal diameter of microcalcifications were the main factors that affected the success of biopsy. CONCLUSION: The clinical application of high frequency ultrasound-guided vacuum-assisted biopsy was an effective option for the diagnosis of breast microcalcifications, especially for the type of microcalcifications with masses and the maximal diameter more than 5 mm. PMID- 22321684 TI - [Robotically assisted coronary artery bypass grafting on beating heart]. AB - OBJECTIVES: To analyze the safety and efficiency of robotically assisted coronary artery bypass grafting (RACABG) on beating heart using da Vinci S system. METHODS: From January 2007 to March 2011, 105 patients underwent RACABG on beating heart through minithoracotomy. There were 77 male and 28 female patients, aged from 33 to 77 years with a mean of (59 +/- 10) years. After establishment of single left lung ventilation, the 3 trocars of da Vinci system were inserted into the left hemithorax, and robotic system was used to harvest the left internal mammary artery (LIMA) and/or right internal mammary artery (RIMA) from the subclavian vein to the internal mammary artery (IMA) bifurcation with skeletonized technique. After positioning the stabilizer, the LIMA was anastomosed manually to the left anterior descending or diagonal branch sequentially on beating heart through left minithoracotomy. The graft flow was evaluated by the Doppler flow meter after anastomosis was completed, and the graft patency was also evaluated by CT angiography or arteriography after surgery. RESULTS: All patients had successful RACABG on the beating heart, and the mean graft flow was (21 +/- 13) ml/min. One patient suffered from cardiac arrest after the first postoperative day, but he recovered soon and CT angiography showed that graft was patent. One patient with preoperative stroke had postoperative pulmonary infection, and was discharged after treatment. After 4 to 5 days, 4 patients received stent placement in right coronary artery or circumflex coronary in distinct hybrid session. There were no deaths or stroke or reintervention. All patients were discharged without complications and followed up. CTA or angiography revealed patent grafts in all patients, and the mean time of follow-up was (30 +/- 12) months. CONCLUSIONS: Robotically assisted coronary artery bypass grafting on beating heart can be performed safely using da Vinci S system. It is a new advanced approach of revascularization not only for patients with single vessel but with multi-vessel lesions as well. PMID- 22321685 TI - [Genomics study of steroid induced femoral head necrosis of rats]. AB - OBJECTIVES: To identify significantly differentially expression genes of steroid induced femoral head necrosis (SINFH) of rats by gene chip, and to find out the potential factors and molecular mechanisms that oxidative stress originate or strengthen the SINFH. METHODS: Twenty Wistar rats were divided into experimental group and control group randomly. E. coli endotoxin was given to all rats at a dose of 20 ug/kg body weight by daily i.p. for two times. Then methylprednisolone (40 mg/kg) or saline was daily injected into the left gluteus muscle of the rats in experimental group and control group respectively. Six weeks later, the mRNA was extracted from the femoral head of rats in every group, and the cDNA were obtained by inverse transcript, then carried out microarray detection. The quantitative RT-PCR was used to confirm the result of microarray, and the differentially expressed genes were analyzed for the functional annotation by gene ontology (GO). RESULTS: Compared to the control group, 190 genes in the experimental group were differentially expressed, with 52 up-regulated and 138 down-regulated. Of these genes, 102 are known (have deposited in GeneBank), while 88 of them are unknown. The known genes can be divided into several families according to their biological functions, such as: oxidative stress, apoptosis, signal transduction, angiogenesis, extracellular matrix, lipid metabolism, and gene transcription related genes. The results of quantitative RT-PCR are consistent with gene-chip results. CONCLUSIONS: The occurrence of SINFH is a complicated process affected by multiple factors and signaling pathways. Our findings indicate that many genes which are involved in different signaling pathways were differentially expressed between SINFH rats and normal rats. PMID- 22321686 TI - [Surgical anatomy of totally trans-oral video-assisted thyroidectomy]. AB - OBJECTIVE: To define the anatomical approach, anatomical planes and related vessels and nerves to create a safe and reproducible combined sublingual and bi vestibular access for trans-oral video-assisted thyroidectomy. METHODS: From November 2009 to May 2011, twenty-five embalmed human specimens were dissected for anatomical information of the cervical region, the mandible region and the supra-hyoid muscles. On twenty fresh frozen human specimens after an experimental trans-oral endoscopic thyroidectomy, the related vascular, neural structures and muscles were evaluated. RESULTS: The optical access port was placed in the midline sublingual. The geniohyoid muscle, mylohyoid muscle and the anterior belly of the digastric muscle were divided in the midline in order to reach the plane under the platysma muscle. The mucosa was sagittal incised bilaterally in the vestibular of oral cavity for working trocar, at the level of the first molar of the mandible. The working trocar reached directly the periosteum of the mandible, under the facial vessel and the marginal branch of facial nerve, and then passed below the platysma muscle into the infra-laryngeal working area. The distance from mental nerve to mandibular midline and between mental nerve and facial artery were (25.8 +/- 0.9) mm and (29.4 +/- 0.9) mm respectively. Anatomical dissections showed that after an experimental trans-oral combined sublingual and bi-vestibular access, all muscles of the floor of the oral cavity as well as the related vascular and neural structures are intact. The maximum nodule size of the resected specimens in the totally trans-oral approach was up to 50 mm. CONCLUSION: The combined sublingual and bi-vestibular access of trans oral video-assisted thyroidectomy is safe and reproducible. PMID- 22321687 TI - The use of podcasts to enhance research-teaching linkages in undergraduate nursing students. AB - An understanding of research is important to enable nurses to provide evidence based care. However, undergraduate nursing students often find research a challenging subject. The purpose of this paper is to present an evaluation of the introduction of podcasts in an undergraduate research module to enhance research teaching linkages between the theoretical content and research in practice and improve the level of student support offered in a blended learning environment. Two cohorts of students (n=228 and n=233) were given access to a series of 5 "guest speaker" podcasts made up of presentations and interviews with research experts within Edinburgh Napier. These staff would not normally have contact with students on this module, but through the podcasts were able to share their research expertise and methods with our learners. The main positive results of the podcasts suggest the increased understanding achieved by students due to the multi-modal delivery approach, a more personal student/tutor relationship leading to greater engagement, and the effective use of materials for revision and consolidation purposes. Negative effects of the podcasts centred around problems with the technology, most often difficulty in downloading and accessing the material. This paper contributes to the emerging knowledge base of podcasting in nurse education by demonstrating how podcasts can be used to enhance research teaching linkages and raises the question of why students do not exploit the opportunities for mobile learning. PMID- 22321688 TI - High latitudes and high genetic diversity: phylogeography of a widespread boreal bird, the gray jay (Perisoreus canadensis). AB - We describe range-wide phylogeographic variation in gray jays (Perisoreus canadensis), a boreal Nearctic corvid that occurs today primarily in recently glaciated regions. Phylogenetic analysis of mitochondrial DNA (1041 base pairs ND2 gene; N=205, 50 localities) revealed four reciprocally monophyletic groups. One widespread clade occurs across the North American boreal zone, from Newfoundland to Alaska and southwest into Utah. Three other clades occur at lower latitudes in the montane West in Colorado, the northern Rocky Mountains, and the Pacific Northwest respectively. The geographic distribution of clades in gray jays corresponds with a general pattern that is emerging for boreal taxa, having one widespread northern clade and one or more geographically restricted southwestern clades. Population genetic analyses indicate that the larger boreal clade is genetically structured and harbors significantly more genetic diversity than those clades occurring at lower latitudes. Species distribution modeling (SDM) revealed multiple putative Pleistocene refugia including several occurring at higher latitudes. We suggest that multiple post-glacial colonization routes, some of which originate from these northern refugia, are responsible for the relatively high genetic diversity at high latitudes. Conversely, lower latitude clades show little variation, probably as a result of historical restriction to smaller geographical areas with smaller long-term population sizes. This 'upside down' pattern of genetic diversity contrasts with the conventional view that populations of north-temperate species occupying previously glaciated habitats should possess lower levels of diversity than their southern counterparts. PMID- 22321690 TI - Memory performance and normalized regional brain volumes in patients with pediatric-onset multiple sclerosis. AB - Studies in adults with multiple sclerosis (MS) have associated regional brain abnormalities with memory impairment. While memory problems in children with MS are often reported, little is known about the neural correlates that may contribute to these difficulties. We measured verbal and nonverbal memory using the Test of Memory and Learning (TOMAL-2) in 32 children and adolescents with MS and 26 age- and sex-matched healthy controls. Memory performance was correlated with volumetric measures of the whole brain, hippocampus, amygdala, and thalamus. Brain volumes were normalized for age and sex using magnetic resonance imaging (MRI) data from the National Institutes of Health MRI Study of Normal Brain development. With the exception of story recall, performance on memory tests was similar to that of the control group. Relative to controls, patient with MS showed reduced volume in the whole brain (p < .001), amygdala (p < .005), and thalamus (p < .001), but not the hippocampus. In the patient group, word-list learning correlated with whole brain volume (r = .53) and hippocampal volume (r = .43), whereas visual recognition memory correlated with thalamic volume (r = .48). Findings are consistent with the well-established role of the hippocampus in learning and consolidation and also highlight the importance of diffuse brain pathology on memory function. PMID- 22321689 TI - A new species of leopard frog (Anura: Ranidae) from the urban northeastern US. AB - Past confusion about leopard frog (genus Rana) species composition in the Tri State area of the US that includes New York (NY), New Jersey (NJ), and Connecticut (CT) has hindered conservation and management efforts, especially where populations are declining or imperiled. We use nuclear and mitochondrial genetic data to clarify the identification and distribution of leopard frog species in this region. We focus on four problematic frog populations of uncertain species affiliation in northern NJ, southeastern mainland NY, and Staten Island to test the following hypotheses: (1) they are conspecific with Rana sphenocephala or R. pipiens, (2) they are hybrids between R. sphenocephala and R. pipiens, or (3) they represent one or more previously undescribed cryptic taxa. Bayesian phylogenetic and cluster analyses revealed that the four unknown populations collectively form a novel genetic lineage, which represents a previously undescribed cryptic leopard frog species, Rana sp. nov. Statistical support for R. sp. nov. was strong in both the Bayesian (pp=1.0) and maximum likelihood (bootstrap=99) phylogenetic analyses as well as the Structure cluster analyses. While our data support recognition of R. sp. nov. as a novel species, we recommend further study including fine-scaled sampling and ecological, behavioral, call, and morphological analyses before it is formally described. PMID- 22321691 TI - Strontium ranelate rebalances bone marrow adipogenesis and osteoblastogenesis in senescent osteopenic mice through NFATc/Maf and Wnt signaling. AB - With aging, bone marrow mesenchymal stromal cell (MSC) osteoblast differentiation decreases whereas MSC differentiation into adipocytes increases, resulting in increased adipogenesis and bone loss. Here, we investigated whether activation of cell signaling by strontium ranelate (SrRan) can reverse the excessive adipogenic differentiation associated with aging. In murine MSC cultures, SrRan increased Runx2 expression and matrix mineralization and decreased PPARgamma2 expression and adipogenesis. This effect was associated with increased expression of the Wnt noncanonical representative Wnt5a and adipogenic modulator Maf and was abrogated by Wnt- and nuclear factor of activated T-cells (NFAT)c antagonists, implying a role for Wnt and NFATc/Maf signaling in the switch in osteoblastogenesis to adipogenesis induced by SrRan. To confirm this finding, we investigated the effect of SrRan in SAMP6 senescent mice, which exhibit decreased osteoblastogenesis, increased adipogenesis, and osteopenia. SrRan administration at a clinically relevant dose level increased bone mineral density, bone volume, trabecular thickness and number, as shown by densitometric, microscanning, and histomorphometric analyses in long bones and vertebrae. This attenuation of bone loss was related to increased osteoblast surface and bone formation rate and decreased bone marrow adipocyte volume and size. The restoration of osteoblast and adipocyte balance induced by SrRan was linked to increased Wnt5a and Maf expression in the bone marrow. The results indicate that SrRan acts on lineage allocation of MSCs by antagonizing the age-related switch in osteoblast to adipocyte differentiation via mechanisms involving NFATc/Maf and Wnt signaling, resulting in increased bone formation and attenuation of bone loss in senescent osteopenic mice. PMID- 22321692 TI - Overexpression of OsHsp17.0 and OsHsp23.7 enhances drought and salt tolerance in rice. AB - Heat shock proteins (Hsps) play an important role in plant stress tolerance. We previously reported that expression of OsHsp17.0 and OsHsp23.7 could be enhanced by heat shock treatment and/or other abiotic stresses. In this paper, stress tolerance assays of transgenic rice plants overexpressing OsHsp17.0 and OsHsp23.7 have been carried out. Both OsHsp17.0-OE and OsHsp23.7-OE transgenic lines demonstrated higher germination ability compared to wild-type (WT) plants when subjected to mannitol and NaCl. Phenotypic analysis showed that transgenic rice lines displayed a higher tolerance to drought and salt stress compared to WT plants. In addition, transgenic rice lines showed significantly lower REC, lower MDA content and higher free proline content than WT under drought and salt stresses. These results suggest that OsHsp17.0 and OsHsp23.7 play an important role in rice acclimation to salt and drought stresses and are useful for engineering drought and salt tolerance rice. PMID- 22321693 TI - Auxin and cytokinin related gene expression during active shoot growth and latent bud paradormancy in Vitis riparia grapevine. AB - Cultural practices for canopy management in grapevines rely on intensive manipulation of shoot architecture to maintain canopy light levels. In contrast to common model plant systems used to study regulation of branch outgrowth, the grapevine has a more complex architecture. The node contains first, second and third order axillary meristems. The prompt bud (N+1) develops into a summer lateral and a latent compound bud develops in the basal node of the summer lateral (N+2, N+3(1,2)). The outgrowth potential of latent buds was determined using common canopy management treatments (shoot tip decapitation and removal of summer laterals and leaves) and monitoring the rate of latent bud outgrowth. Two shoot node regions (apical and basal) with differential outgrowth potential were characterized and it was noted that the shoot tip, summer laterals and leaves in addition to node position contributed to the inhibition of latent bud outgrowth. To advance the understanding of the molecular regulation of bud outgrowth and paradormancy in the complex shoot architecture of grapevines, the expression of auxin and cytokinin genes involved in branching (amidase (VrAMI1), PINFORMED-3 (VrPIN3) and isopentenyl transferase (VrIPT)) were monitored in shoot tips and differentially aged buds of Vitis riparia grapevine shoots. In addition, Histone 3 (VrH3) and a hexose transporter (VrHT1) expression were monitored as a measure of tissue activity. The expression of VrAMI1 and VrPIN3 remained constant in actively growing shoot tips and decreased significantly with increasing bud maturation in paradormant buds. VrHT1 expression was greater in buds than in any other plant tissue tested. VrHT1 may have the potential to be used as an indicator of paradormancy status in grapevines. These characterizations in the complex architecture of the grapevine provide an excellent model system for molecular analysis of bud outgrowth and shoot architecture development. PMID- 22321694 TI - Protective effect of (2'S)-columbianetin from Corydalis heterocarpa on UVB induced keratinocyte damage. AB - A salt tolerant plant, Corydalis heterocarpa has been used as a folk medicine to treat travail and spasm. Recent studies have also reported antioxidant and antiinflammatory activities of compounds isolated from C. heterocarpa. In this study, the protective effect of (2'S)-columbianetin isolated from C. heterocarpa on UVB-induced human keratinocyte (HaCaT) damage was investigated. First, the appropriate energy level of UVB irradiation was determined using MTT and LDH assays. And then the protective effect of (2'S)-columbianetin on UVB induced HaCaT damage was evaluated by measuring; the changes in cell viability, LDH release level, ROS generation, cell cycle arrest and MMP expression levels. Finally, the effect of compound on MAPK and AP-1 signaling pathways were studied to understand the underlying signaling mechanisms. Result demonstrated that the presence of (2'S)-columbianetin suppressed the reactive oxygen species (ROS) generation, cell cycle arrest at sub-G1 phase and down regulation of MMP expression in UVB treated HaCaT cells. Furthermore, stress activated signaling pathways (ASK1-MAPK) and AP-1 signaling pathway were regulated by (2'S) columbianetin treatment. These results suggest that (2'S)-columbianetin could be effectively used to protect human keratinocytes from UVB induced damage. PMID- 22321695 TI - Method: automatic segmentation of mitochondria utilizing patch classification, contour pair classification, and automatically seeded level sets. AB - BACKGROUND: While progress has been made to develop automatic segmentation techniques for mitochondria, there remains a need for more accurate and robust techniques to delineate mitochondria in serial blockface scanning electron microscopic data. Previously developed texture based methods are limited for solving this problem because texture alone is often not sufficient to identify mitochondria. This paper presents a new three-step method, the Cytoseg process, for automated segmentation of mitochondria contained in 3D electron microscopic volumes generated through serial block face scanning electron microscopic imaging. The method consists of three steps. The first is a random forest patch classification step operating directly on 2D image patches. The second step consists of contour-pair classification. At the final step, we introduce a method to automatically seed a level set operation with output from previous steps. RESULTS: We report accuracy of the Cytoseg process on three types of tissue and compare it to a previous method based on Radon-Like Features. At step 1, we show that the patch classifier identifies mitochondria texture but creates many false positive pixels. At step 2, our contour processing step produces contours and then filters them with a second classification step, helping to improve overall accuracy. We show that our final level set operation, which is automatically seeded with output from previous steps, helps to smooth the results. Overall, our results show that use of contour pair classification and level set operations improve segmentation accuracy beyond patch classification alone. We show that the Cytoseg process performs well compared to another modern technique based on Radon Like Features. CONCLUSIONS: We demonstrated that texture based methods for mitochondria segmentation can be enhanced with multiple steps that form an image processing pipeline. While we used a random-forest based patch classifier to recognize texture, it would be possible to replace this with other texture identifiers, and we plan to explore this in future work. PMID- 22321696 TI - Adenoma detection rate is not influenced by full-day blocks, time, or modified queue position. AB - BACKGROUND: Recent studies have shown the adenoma detection rate (ADR) to decrease from endoscopist fatigue. OBJECTIVE: Our primary objective was to evaluate the afternoon ADR in half-day versus full-day blocks. Secondary objectives were to determine whether time or complexity of prior procedures (modified queue position) influence ADR. DESIGN: Retrospective chart review on consecutive colonoscopies. SETTING: Tertiary-care teaching hospital. PATIENTS: This study involved all patients in our database who were over age 45 and who underwent screening and surveillance colonoscopies. MAIN OUTCOME MEASUREMENT: ADR. RESULTS: A total of 3085 patients were included in the study, with an overall 31% ADR. Of these procedures, 2148 (70%) were done in the morning, and 937 (30%) were done in the afternoon (512 full-day block, 425 half-day block). By multivariate analysis, there was no difference in ADR between full-day blocks compared with afternoon-only blocks (35% vs 32%; odds ratio [OR] 1.1; 95% confidence interval [CI], 0.8-1.5; P = .2). For all afternoon colonoscopies, no decrease in ADR was noted with increasing queue position (P = .9) or time (P = .3). In addition, no difference was found comparing ADR between all afternoon colonoscopies versus morning colonoscopies (33% vs 30%; OR 1.1; CI, 1.0-1.3; P = .1). No difference was found for advanced adenomas and number of adenomas between either afternoon-only blocks versus afternoon colonoscopy in full-day blocks or morning versus all afternoon cases. LIMITATIONS: Retrospective study; not all withdrawal times were recorded; trainees performed some of the procedures. CONCLUSION: Our data show that colonoscopy can be performed in full-day blocks and 30-minute slots without compromising ADR. PMID- 22321698 TI - Automatic recognition of conceptualization zones in scientific articles and two life science applications. AB - MOTIVATION: Scholarly biomedical publications report on the findings of a research investigation. Scientists use a well-established discourse structure to relate their work to the state of the art, express their own motivation and hypotheses and report on their methods, results and conclusions. In previous work, we have proposed ways to explicitly annotate the structure of scientific investigations in scholarly publications. Here we present the means to facilitate automatic access to the scientific discourse of articles by automating the recognition of 11 categories at the sentence level, which we call Core Scientific Concepts (CoreSCs). These include: Hypothesis, Motivation, Goal, Object, Background, Method, Experiment, Model, Observation, Result and Conclusion. CoreSCs provide the structure and context to all statements and relations within an article and their automatic recognition can greatly facilitate biomedical information extraction by characterizing the different types of facts, hypotheses and evidence available in a scientific publication. RESULTS: We have trained and compared machine learning classifiers (support vector machines and conditional random fields) on a corpus of 265 full articles in biochemistry and chemistry to automatically recognize CoreSCs. We have evaluated our automatic classifications against a manually annotated gold standard, and have achieved promising accuracies with 'Experiment', 'Background' and 'Model' being the categories with the highest F1-scores (76%, 62% and 53%, respectively). We have analysed the task of CoreSC annotation both from a sentence classification as well as sequence labelling perspective and we present a detailed feature evaluation. The most discriminative features are local sentence features such as unigrams, bigrams and grammatical dependencies while features encoding the document structure, such as section headings, also play an important role for some of the categories. We discuss the usefulness of automatically generated CoreSCs in two biomedical applications as well as work in progress. AVAILABILITY: A web-based tool for the automatic annotation of articles with CoreSCs and corresponding documentation is available online at http://www.sapientaproject.com/software http://www.sapientaproject.com also contains detailed information pertaining to CoreSC annotation and links to annotation guidelines as well as a corpus of manually annotated articles, which served as our training data. CONTACT: liakata@ebi.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22321700 TI - Mytoe: automatic analysis of mitochondrial dynamics. AB - SUMMARY: We present Mytoe, a tool for analyzing mitochondrial morphology and dynamics from fluorescence microscope images. The tool provides automated quantitative analysis of mitochondrial motion by optical flow estimation and of morphology by segmentation of individual branches of the network-like structure of the organelles. Mytoe quantifies several features of individual branches, such as length, tortuosity and speed, and of the macroscopic structure, such as mitochondrial area and degree of clustering. We validate the methods and apply them to the analysis of sequences of images of U2OS human cells with fluorescently labeled mitochondria. AVAILABILITY: Source code, Windows software and Manual available at http://www.cs.tut.fi/%7Esanchesr/mito SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. CONTACT: eero.lihavainen@tut.fi; andre.ribeiro@tut.fi. PMID- 22321699 TI - A novel significance score for gene selection and ranking. AB - MOTIVATION: When identifying differentially expressed (DE) genes from high throughput gene expression measurements, we would like to take both statistical significance (such as P-value) and biological relevance (such as fold change) into consideration. In gene set enrichment analysis (GSEA), a score that can combine fold change and P-value together is needed for better gene ranking. RESULTS: We defined a gene significance score pi-value by combining expression fold change and statistical significance (P-value), and explored its statistical properties. When compared to various existing methods, pi-value based approach is more robust in selecting DE genes, with the largest area under curve in its receiver operating characteristic curve. We applied pi-value to GSEA and found it comparable to P-value and t-statistic based methods, with added protection against false discovery in certain situations. Finally, in a gene functional study of breast cancer profiles, we showed that using pi-value helps elucidating otherwise overlooked important biological functions. AVAILABILITY: http://gccri.uthscsa.edu/Pi_Value_Supplementary.asp CONTACT: xy@ieee.org, cheny8@uthscsa.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22321701 TI - In silico methods combined with expert knowledge rule out mutagenic potential of pharmaceutical impurities: an industry survey. AB - With the increasing emphasis on identification and low level control of potentially genotoxic impurities (GTIs), there has been increased use of structure-based assessments including application of computerized models. To date many publications have focused on the ability of computational models, either individually or in combination, to accurately predict the mutagenic effects of a chemical in the Ames assay. Typically, these investigations take large numbers of compounds and use in silico tools to predict their activity with no human interpretation being made. However, this does not reflect how these assessments are conducted in practice across the pharmaceutical industry. Current guidelines indicate that a structural assessment is sufficient to conclude that an impurity is non-mutagenic. To assess how confident we can be in identifying non-mutagenic structures, eight companies were surveyed for their success rate. The Negative Predictive Value (NPV) of the in silico approaches was 94%. When human interpretation of in silico model predictions was conducted, the NPV increased substantially to 99%. The survey illustrates the importance of expert interpretation of in silico predictions. The survey also suggests the use of multiple computational models is not a significant factor in the success of these approaches with respect to NPV. PMID- 22321702 TI - Sitafloxacin resistance in Helicobacter pylori isolates and sitafloxacin-based triple therapy as a third-line regimen in Japan. AB - The third-line treatment regimen for Helicobacter pylori after failure of clarithromycin- and metronidazole-based therapies is not yet established. Sitafloxacin (STX) is a quinolone that possesses potent in vitro activity against H. pylori. In this study, the susceptibility of H. pylori isolates to STX was examined and the efficacy of STX-based triple therapy as a third-line regimen was evaluated. STX showed minimum inhibitory concentrations (MICs) of <=1 MUg/mL against all 100 H. pylori isolates, and the MIC(90) (MIC for 90% of the organisms) of STX was 5 log(2) dilutions lower than that of levofloxacin (LVX). The MIC(50) (MIC for 50% of the organisms) of STX against gyrA mutants was 0.12 MUg/mL and was significantly lower than that of LVX (8 MUg/mL). The activity of STX at pH 5.5 was significantly less than that at pH 7.0. In the clinical trial, 28 patients with two eradication failures were treated with STX-based triple therapy [rabeprazole 10 mg twice daily (b.i.d.), amoxicillin 750 mg b.i.d. and STX 100mg b.i.d. for 7 days]. The eradication rate was 75% using intention-to treat analysis and 80% using per-protocol analysis. Two gyrA mutant strains were eradicated. Amongst participants, a low pepsinogen I/II ratio was associated with successful eradication. These results suggest that STX could be active against most clinical H. pylori isolates and that STX-based triple therapy is a promising and safe third-line therapy. PMID- 22321703 TI - Factors that influence acceptance of web-based e-learning systems for the in service education of junior high school teachers in Taiwan. AB - Web-based e-learning is not restricted by time or place and can provide teachers with a learning environment that is flexible and convenient, enabling them to efficiently learn, quickly develop their professional expertise, and advance professionally. Many research reports on web-based e-learning have neglected the role of the teacher's perspective in the acceptance of using web-based e-learning systems for in-service education. We distributed questionnaires to 402 junior high school teachers in central Taiwan. This study used the Technology Acceptance Model (TAM) as our theoretical foundation and employed the Structure Equation Model (SEM) to examine factors that influenced intentions to use in-service training conducted through web-based e-learning. The results showed that motivation to use and Internet self-efficacy were significantly positively associated with behavioral intentions regarding the use of web-based e-learning for in-service training through the factors of perceived usefulness and perceived ease of use. The factor of computer anxiety had a significantly negative effect on behavioral intentions toward web-based e-learning in-service training through the factor of perceived ease of use. Perceived usefulness and motivation to use were the primary reasons for the acceptance by junior high school teachers of web based e-learning systems for in-service training. PMID- 22321704 TI - Secreted protein acidic and rich in cysteine (SPARC) is associated with nasopharyngeal carcinoma metastasis and poor prognosis. AB - BACKGROUND: The aim of the present study was to analyse the expression of Secreted protein acidic and rich in cysteine (SPARC) in nasopharyngeal carcinoma (NPC) specimens, and to evaluate its correlation with clinicopathologic features, including survival of patients with NPC. METHODS: NPC tissue microarrays (TMAs) were constructed from Sun Yat-sen University Cancer Center (SYSUCC), another three centers on mainland China, Singapore and Hong Kong. Using quantitative RT PCR and Western-blotting techniques, we detected mRNA and protein expression of SPARC in NPC cell lines and immortalized nasopharyngeal epithelial cells (NPECs) induced by Bmi-1 (NPEC2 Bmi-1). The difference of SPARC expression in the cell lines was tested using a t-test method. The relationship between the SPARC expression and clinicopathological data was assessed by chi-square. Survival analysis was estimated using the Kaplan-Meier approach with log-rank test. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models. RESULTS: The expression levels of SPARC mRNA and protein were markedly higher in NPC cell lines than in NPEC2 Bmi 1. Especially, the expression levels of SPARC mRNA and protein were much lower in the 6-10B than in the 5-8 F (P = 0.002, P = 0.001). SPARC immunostaining revealed cytoplasmic localization in NPC cells and no staining in the stroma and epithelium. In addition, high level of SPARC positively correlated with the status of distant metastasis (P = 0.001) and WHO histological classification (P = 0.023). NPC patients with high SPARC expression also had a significantly poorer prognosis than patients with low SPARC expression (log-rank test, P < 0.001), especially patients with advanced stage disease (log-rank, P < 0.001). Multivariate analysis suggested that the level of SPARC expression was an independent prognostic indicator for the overall survival of patients with NPC (P < 0.001). CONCLUSIONS: SPARC expression is common in NPC patients. Our data shows that elevated SPARC expression is a potential unfavorable prognostic factor for patients with NPC. PMID- 22321705 TI - [A case-control study on the risk factors for lower respiratory tract infection by Stenotrophomonas maltophilia in a medical intensive care unit]. AB - OBJECTIVE: To explore the risk factors for lower respiratory tract infection by Stenotrophomonas maltophilia in the medical intensive care unit (MICU) in Fujian Provincial Hospital. METHODS: A 1:4 matched case-control study was carried out in the MICU in Fujian Provincial Hospital. Thirty-five patients with hospital acquired lower respiratory tract infection by Stenotrophomonas maltophilia from 2007 to 2010 were included as cases, and 140 patients without lower respiratory tract infection served as controls. The case group included 22 cases with respiratory diseases, 4 with cerebrovascular diseases, 4 with cardiovascular diseases, 1 with hemorrhage of the digestive tract, 1 with acute pancreatitis, 1 with chronic kidney disease, 1 with cervical cancer and 1 with Alzheimer's disease. While the control group included 30 cases with respiratory diseases, 44 with cerebrovascular diseases, 14 with cardiovascular diseases, 2 with malignant tumors and 50 with others. Patients' information, general situation before being admitted to MICU, drug therapy, invasive procedures and hospital-acquired infection were analyzed. Conditional logistic regression was performed to identify independent risk factors. RESULTS: Univariate analysis showed that factors such as more than 4 underlying diseases (OR = 4.63), APACHE-II score >= 20(OR = 10.29), stay in the general ward more than 1 week before being admitted to MICU, treatment with more than 3 kinds of antibiotics (OR = 8.03), endotracheal intubation (OR = 4.10) or tracheotomy (OR = 50.29) and mechanical ventilation (OR = 7.95) were risk factors for hospital-acquired lower respiratory tract infection by Stenotrophomonas maltophilia. Multivariate logistic regression showed that variables such as APACHE-II score (OR = 8.39), kinds of antibiotics used (OR = 5.96) and tracheotomy (OR = 28.92) were independent risk factors (P < 0.01). CONCLUSIONS: Underlying diseases, the severity of diseases, tracheotomy, mechanical ventilation, and the use of wide-spectrum antibiotics are important risk factors for lower respiratory tract infection by Stenotrophomonas maltophilia in MICU. To identify these factors and take preventive measures earlier may be useful for decreasing Stenotrophomonas maltophilia infection related mortality. PMID- 22321706 TI - [Interventional bronchoscopy with the use of mechanical ventilation by larynx mask or tracheal intubation under general anesthesia]. AB - OBJECTIVE: To explore and evaluate the technique of performing interventional bronchoscopy by using mechanical ventilation with larynx mask or tracheal intubation under general anesthesia. METHODS: From July 2009 to January 2010, 29 patients received interventional bronchoscopy by using mechanical ventilation with larynx mask or tracheal intubation under general anesthesia. Airway pressure and tidal volume before and after bronchoscope insertion, arterial blood gas analysis during interventional bronchoscopy, complications and operation time were recorded. The factors influencing ventilation effects were evaluated. RESULTS: All the patients' condition were kept stable during interventional bronchoscopy and no severe complications occurred. Tidal volume was reduced by 27.1%, while peak airway pressure, plateau pressure and mean airway pressure were increased by 63.1%, 43.7% and 32.4% following insertion of the bronchoscope respectively. Patients using tracheal intubation had their peak pressure increased by 79.3%, which was higher than that of patients using larynx mask (55.3%). CONCLUSIONS: Interventional bronchoscopy by using mechanical ventilation with larynx mask or tracheal intubation under general anesthesia was safe and reliable. Although peak airway pressure increased following insertion of bronchoscope, the mean airway pressure was maintained in a low level. When performing interventional bronchoscopy during mechanical ventilation, the inside diameter of larynx mask and tracheal intubation should be as large as possible to minimize airway pressure and auto-PEEP. PMID- 22321707 TI - [Effects of rosiglitazone on peroxisome proliferator activated receptor-gamma pathway in patients with chronic obstructive pulmonary disease]. AB - OBJECTIVE: To explore the effects of rosiglitazone on peroxisome proliferator activated receptor-gamma (PPAR-gamma), nuclear factor-kappaB and tumor necrosis factor-alpha (TNF-alpha) in patients with chronic obstructive pulmonary disease (COPD). METHODS: From Apr. 2010 to Nov. 2010, 30 patients with acute exacerbations of COPD, 22 males and 8 females, age 54 - 87 (mean 72 +/- 9) years and 24 healthy controls, 18 males and 6 females, age 52 - 80 (mean 69 +/- 10) years were included. The peripheral blood mononuclear cells (PBMCs) were isolated from venous blood and then cultured. On the basis of the treatment given, the PBMCs of COPD patients were divided into 3 groups: non-treatment group, rosiglitazone treatment group (rosiglitazone group) and rosiglitazone and GW9662 treatment group (combined treatment group). Cells from the healthy controls (control group) did not receive any drug treatment. The mRNA expression of PPAR gamma and NF-kappaB was measured with real-time PCR. The protein expression and nuclear translocation of PPAR-gamma and NF-kappaB were detected using immunofluorescence with laser scanning confocal microscopy. The TNF-alpha level in culture supernatant was measured with ELISA. One-way ANOVA and LSD-t test and the Pearson correlation coefficient were used for statistical analysis. RESULTS: The mRNA and protein levels of PPAR-gamma were lower in the non-treatment group (0.52 +/- 0.10, 55 +/- 11) than those in the control group (1, 85 +/- 9), while the levels of NF-kappaB mRNA and protein were higher in the non-treatment group (1.69 +/- 0.07, 145 +/- 17) than those in the control group (1, 118 +/- 7). The mRNA and protein levels of PPAR-gamma in the rosiglitazone group (4.47 +/- 0.11, 204 +/- 12) were significantly increased compared with the non-treatment group, while the mRNA and protein levels of NF-kappaB (0.33 +/- 0.04, 59 +/- 14) were remarkably decreased compared with the non-treatment group. The mRNA and protein levels of PPAR-gamma (2.25 +/- 0.31, 142 +/- 23) were significantly decreased in the combined treatment group compared to the rosiglitazone group, but higher compared with the non-treatment group, while the mRNA and protein levels of NF kappaB (0.64 +/- 0.02, 90 +/- 10) were increased compared with the rosiglitazone group, but decreased compared to the non-treatment group (F = 29.21 - 567.42, all P < 0.01). The TNF-alpha level was significantly higher in the non-treatment group (96.2 +/- 1.4) ug/L than that in the control group (85.3 +/- 1.0) ug/L. The TNF-alpha level in the rosiglitazone group (63.0 +/- 2.5) ug/L was remarkably decreased compared with the non-treatment group, while that in the combined treatment group (83.3 +/- 1.9) ug/L was increased compared with the rosiglitazone group, but decreased compared to the non-treatment group (F = 293.72, P < 0.01). The proteins of PPAR-gamma and NF-kappaB were respectively located in cytoplasm and in nucleus in the non-treatment group, meanwhile they were located in both cytoplasm and nucleus in the control group. PPAR-gamma protein was translocated from cytoplasm into nucleus and NF-kappaB protein was translocated from nucleus into cytoplasm in the rosiglitazone group. In the combined treatment group, PPAR gamma protein translocated from nucleus into cytoplasm and NF-kappaB protein partly translocated from cytoplasm into nucleus. By linear correlation analysis, PPAR-gamma protein was negatively correlated with NF-kappaB protein and TNF-alpha level (r = -0.935, -0.924, all P < 0.01), while NF-kappaB protein was positively correlated to TNF-alpha level (r = 0.846, P < 0.01). CONCLUSIONS: The expression and activity of PPAR-gamma were decreased in COPD patients. PPAR-gamma agonist rosiglitazone inhibited inflammation in COPD through upregulating the expression and activity of PPAR-gamma and inhibition of NF-kappaB and TNF-alpha. It suggests that PPAR-gamma may play an important role in the inflammation of COPD. PMID- 22321708 TI - [Event-related potentials P(300) with memory function in obstructive sleep apnea syndrome]. AB - OBJECTIVE: To explore the variability of event-related potentials P(300) and memory function in patients with obstructive sleep apnea syndrome(OSAS). METHODS: Polysomnography (PSG) event-related potentials (ERPs) P(300) and Wechsler Memory Scale (WMS) were detected in 30 subjects with OSAS and 20 normal controls. RESULTS: The memory quotient [(86 +/- 13) scores] in the OSAS group was significantly lower than that in the control group (P < 0.01). The latency of P(300) [(410 +/- 80) ms at Cz and (409 +/- 80) ms at Pz] in the OSAS group was significantly longer than that in the control group (P < 0.01). In the OSAS group, the latency of P(300) was correlated negatively with the memory quotient and nocturnal hypoxemia, but positively with apea/hypopnea index (AHI, P < 0.01). CONCLUSION: OSAS has memory deficit, which can be evaluated comprehensively by P(300) and WMS. The longer latency of P(300) might be regarded as one of the electrophysiological markers to indicate the severity of cognition in OSAS. Recurrent attacks of nocturnal intermittent hypoxemia may cause the regional brain damage related to cognition defect. PMID- 22321709 TI - [An epidemiological study of chronic obstructive pulmonary disease in greenhouse farmers in Liaoning Province from 2006 to 2009]. AB - OBJECTIVE: To investigate the prevalence of chronic obstructive pulmonary disease (COPD) in greenhouse farmers in Liaoning Province from 2006 to 2009. METHODS: By stratified-cluster random sampling, a survey of 5420 greenhouse farmers working in 835 plastic greenhouses was performed using uniform questionnaires in Shenyang, Chaoyang, and Jinzhou during 2006 and 2009. Physical examination and lung function tests were performed for all of the farmer. Blood routine examinations, blood gas analysis, and chest X-ray were performed for some of the subjects with respiratory symptoms and healthy controls. The chi-square test was used for comparison of the 2 sample rates, and the chi-square segmentation method for more. RESULTS: The overall prevalence of COPD in greenhouse farmers in Liaoning Province was 17.5% (947/5420). Most patients were elderly, especially at the age of 50 years or older. The prevalence of COPD in greenhouse farmers in the plain areas was 15.6% (464/2981), which was lower than that in the mountains (20.2%, 246/1220) and coastal areas (19.4%, 237/1219), with a significant difference (the value of chi(2) were 13.04 and 9.35, all P < 0.0125). The prevalence of COPD in vegetable greenhouse farmers was 12.6% (273/2168), which was lower than that in fungus greenhouse farmers (24.3%, 263/1084), poultry greenhouse farmers (20.8%, 169/813) and flowers greenhouse farmers (17.9%, 242/1355), with a significant difference (the value of chi(2) were 71.49, 31.44 and 18.54, all P < 0.007). The prevalence of COPD was the highest (28.3%, 137/485) in farmers who had worked in the greenhouses for 3 to 5 years. CONCLUSIONS: The overall prevalence of COPD in greenhouse farmers in Liaoning Province was higher than that reported in the rural areas nationally. Attention should be paid to the prevention and control of COPD in greenshouse farmers. PMID- 22321710 TI - [Effects of transient receptor potential melastatin 8 cation channels on inflammatory reaction induced by cold temperatures in human airway epithelial cells]. AB - OBJECTIVE: To explore the role of transient receptor potential melastatin 8 cation channels (TRPM8) in cold-induced production of inflammatory factors in airway epithelial cells and related signal transduction mechanism. METHODS: The 16HBE human airway epithelial cells were stimulated with cold temperature (18 degrees C). In intervention experiments, cells were pretreated with TRPM8 channel antagonist BCTC, protein kinase C (PKC) specific inhibitor calphostin C and transfected with TRPM8 shRNA or control shRNA respectively, and thereafter cold stimulation was applied. Cells were divided into 6 groups: a control group (incubated at 37 degrees C), a cold stimulation group, a cold stimulation + BCTC group, a cold stimulation + TRPM8 shRNA group, a cold stimulation + control shRNA group, a cold stimulation + calphostin C group. Western blot was performed to show the extent of knockdown in TRPM8 protein expression in the TRPM8 shRNA transfected cells. Dynamics of relative concentration of intracellular Ca(2+) in the former 5 groups were measured by calcium imaging techniques. Images were taken at one frame per 10 seconds. The levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-alpha mRNA and protein were detected by real-time PCR and ELISA respectively. RESULTS: The highest relative concentration of intracellular calcium in cold stimulation group (2.36 +/- 0.24) was higher than that of control group (1.01 +/- 0.02) (t = 12.52, P < 0.01). BCTC and TRPM8 shRNA reduced intracellular calcium (1.05 +/- 0.09, 1.08 +/- 0.09), compared with single cold stimulation group (t = 6.69 and 9.12, all P < 0.01). IL-6, IL-8, TNF-alpha mRNA and protein in cold stimulation group[0.66 +/- 0.16, 0.77 +/- 0.15, 0.73 +/- 0.09 and (92 +/- 13) ng/L, (125 +/- 22) ng/L, (88 +/- 12) ng/L ] were significantly higher than those in control group [0.37 +/- 0.08, 0.32 +/- 0.07, 0.48 +/- 0.10 and (52 +/- 8) ng/L, (50 +/- 9) ng/L, (61 +/- 8) ng/L] (t = 3.20 - 6.26, all P < 0.05). IL-6 mRNA, IL-8 mRNA, TNF-alpha mRNA and protein in cold stimulation + BCTC group [0.42 +/- 0.09, 0.52 +/- 0.13, 0.52 +/- 0.12 and (72 +/- 8) ng/L, (92 +/- 14) ng/L, (68 +/- 11) ng/L], cold stimulation + TRPM8 shRNA group [0.41 +/- 0.10, 0.49 +/- 0.08, 0.50 +/- 0.08 and (60 +/- 12) ng/L, (89 +/- 14) ng/L, (68 +/ 11) ng/L] and cold stimulation + calphostin C group [0.40 +/- 0.07, 0.44 +/- 0.09, 0.47 +/- 0.08 and (69 +/- 9) ng/L, (86 +/- 15) ng/L, (61 +/- 10) ng/L] were significantly lower than those in cold stimulation group (t = 2.47 - 4.21, all P < 0.05). IL-6 mRNA, IL-8 mRNA, TNF-alpha mRNA and protein in cold stimulation + control shRNA group [0.61 +/- 0.10, 0.69 +/- 0.11, 0.64 +/- 0.13 and (89 +/- 13) ng/L, (118 +/- 20) ng/L, (79 +/- 13) ng/L] showed no significant change, compared with cold stimulation group (t = 0.35 - 1.12, all P > 0.05). CONCLUSION: Cold temperature may induce Ca(2+) influx and up-regulate IL-6, IL-8, and TNF-alpha expression in 16HBE cells by activating the TRPM8 ion channels, and this is via a signaling pathway involving PKC. PMID- 22321711 TI - [Analysis of the antimycobacterial activities of rifabutin and the relationship between drug-resistance and rpoB mutations of Mycobacterium tuberculosis]. AB - OBJECTIVE: To compare the antimycobacterial activities of rifampicin (RFP) and rifabutin (RBT), and to evaluate the correlation between RBT resistance and genetic alterations in the rpoB gene. METHODS: The microplate-based alamar blue assay (MABA) method was performed to detect the antimycobacterial activities of RFP and RBT in 168 strains of Mycobacterium tuberculosis (M. tuberculosis). Meanwhile, we also analyzed the 81 bp core region of rpoB gene by DNA sequencing. The rate of gene mutations was analyzed by chi-square test. RESULTS: RBT was sensitive for all of the 66 RFP-sensitive strains with no mutations in 81 bp core region of rpoB gene. But of the 102 RFP-resistant strains, 76 strains were also resistant to RBT. Cross resistance between RFP and RBT was 74.5% (76/102). Alterations at codons 516, 526, 531 in the rpoB gene correlated with resistance to both RFP and RBT. While point mutations at codons 511 and 533 possibly influenced the susceptibility to RFP but not to RBT. The mutation rate (92.1%, 70/76) of rpoB gene of RBT-resistant strains was significantly higher than that (23.9%, 22/92) of RBT-sensitive strains (chi(2) = 78.12, P < 0.05). CONCLUSIONS: RBT was more active against M. tuberculosis as compared to RFP. The RFP-resistant strains with MIC <= 4 mg/L were still susceptible to RBT. Our results suggest that analysis of genetic alterations in the rpoB gene is useful for predicting RFP-resistance, and may have implications for evaluating RBT-resistance. PMID- 22321712 TI - [Immunologic mechanism of chronic obstructive pulmonary disease]. PMID- 22321713 TI - [The progress of drug resistance detection in Mycobacterium tuberculosis]. PMID- 22321714 TI - [Advances in lung transplantation for pulmonary lymphangioleiomyomatosis]. PMID- 22321715 TI - [Role of aldose reductase in the treatment of asthma]. PMID- 22321716 TI - [Establishment and application of chronic intermittent hypoxia animal model mimicking sleep apnea]. PMID- 22321717 TI - Gender-specific relationships between alcohol drinking patterns and metabolic syndrome: the Korea National Health and Nutrition Examination Survey 2008. AB - OBJECTIVE: To examine gender-specific relationships between alcohol drinking patterns (average drinking frequency, typical drinking quantity and frequency of binge drinking) and the prevalence of metabolic syndrome (MetS) and its components in the Korean population. DESIGN: Cross-sectional study using complex sampling design analyses. SETTING: The Korea National Health and Nutrition Examination Survey IV, which was conducted in 2008. SUBJECTS: Current drinkers (n 3793, 1963 men and 1830 women). RESULTS: After adjusting for confounders (age, educational level, income, physical activity, smoking, energy intake and drinking frequency in the analysis for drinking quantity), the associations of drinking quantity and frequency of binge drinking with the prevalence of MetS were gender specific. Seven or more drinks for men and >= 3 drinks for women per typical occasion and binge drinking >= 1 time/week for both sexes resulted in significantly higher odds for the prevalence of MetS compared with men and women who had 1 or 2 drinks and no instances of binge drinking. The association of drinking quantity and the criteria of MetS was stronger for men with high blood pressure and abdominal obesity, whereas it was stronger for women with high glucose. Binge drinking frequency was dose-dependently associated with high TAG, high glucose, high blood pressure and abdominal obesity in men, and with high glucose and high blood pressure in women. Interestingly, average drinking frequency was not associated with the prevalence of MetS in either sex. CONCLUSIONS: Higher drinking quantity and frequent binge drinking are indicators of a higher prevalence of MetS, and the association strength is thought to be gender-specific. PMID- 22321718 TI - Maximising the output of osteoarthritis research: the ARRIVE guidelines. PMID- 22321719 TI - What constitutes an "animal model of osteoarthritis"--the need for consensus? AB - OBJECTIVE: To review the use of animal models of osteoarthritis (OA) with regard to their utility for investigation of the mechanisms and regulation of structural pathology and pain. METHODS: PubMed searches were conducted using separate clusters of terms to retrieve articles on (i) models of structural joint damage in genetically-modified (GM) mice, and (ii) models of OA joint pain. The papers were reviewed to investigate whether there was evidence that the research outcome was dependent on the model used. RESULTS: Out of a total of 109 separate GM mice strains identified in which an effect on OA was reported, 15 had been studied using more than one arthritis model. In 10/15 the same effect of the GM on arthritis was reported in at least two different models. In 5/15 the effect of the GM on arthritis structural pathology was different, and sometimes opposite, when comparing two or more induction methods. A total of 112 publications were retrieved in which pain/disability was examined in a model suggested to represent OA. The induction methods used most commonly to study "OA pain" were distinct from those most often used to investigate the pathophysiology and regulation of structural joint damage. Four papers directly comparing pain mechanisms in different models were identified, with 3/4 describing differences in nociceptive pathways. CONCLUSIONS: The available data indicates that the molecular mechanisms of both joint structural damage and pain may be distinct in animal models of OA induced or initiated by different means. This suggests the need to continue using multiple OA animal models but that the subsequent interpretation of the data and its extrapolation to the human condition must be more precise. PMID- 22321720 TI - Application of second derivative spectroscopy for increasing molecular specificity of Fourier transform infrared spectroscopic imaging of articular cartilage. AB - OBJECTIVE: Fourier transform infrared (FT-IR) spectroscopic imaging is a promising method that enables the analysis of spatial distribution of biochemical components within histological sections. However, analysis of FT-IR spectroscopic data is complicated since absorption peaks often overlap with each other. Second derivative spectroscopy is a technique which enhances the separation of overlapping peaks. The objective of this study was to evaluate the specificity of the second derivative peaks for the main tissue components of articular cartilage (AC), i.e., collagen and proteoglycans (PGs). MATERIALS AND METHODS: Histological bovine AC sections were measured before and after enzymatic removal of PGs. Both formalin-fixed sections (n = 10) and cryosections (n = 6) were investigated. Relative changes in the second derivative peak heights caused by the removal of PGs were calculated for both sample groups. RESULTS: The results showed that numerous peaks, e.g., peaks located at 1202 cm(-1) and 1336 cm(-1), altered less than 5% in the experiment. These peaks were assumed to be specific for collagen. In contrast, two peaks located at 1064 cm(-1) and 1376 cm(-1) were seen to alter notably, approximately 50% or more. These peaks were regarded to be specific for PGs. The changes were greater in cryosections than formalin-fixed sections. CONCLUSIONS: The results of this study suggest that the second derivative spectroscopy offers a practical and more specific method than routinely used absorption spectrum analysis methods to obtain compositional information on AC with FT-IR spectroscopic imaging. PMID- 22321721 TI - Taenia crassiceps WFU cysticerci synthesize corticosteroids in vitro: metyrapone regulates the production. AB - Taenia solium and Taenia crassiceps WFU cysticerci and tapeworms have the ability to synthesize sex steroid hormones and have a functional 3beta-hydroxisteroid dehydrogenase. Corticosteroids (CS) like corticosterone and dexamethasone have been shown to stimulate in vitro estrogen production by Taenia crassiceps WFU cysticerci. The aim of this work was to study the ability of T. crassiceps WFU cysticerci to synthesize corticosteroids, and the effect of the inhibitor metyrapone on the CS synthesis. For this purpose T. crassiceps WFU cysticerci were obtained from the abdominal cavity of mice, thoroughly washed and pre incubated in multiwells for 24 h in DMEM plus antibiotics/antimycotics. The tritiated CS precursor progesterone ((3)H-P4) was added to the culture media and parasites cultured for different periods. Blanks containing the culture media plus the (3)H-P4 were simultaneously incubated. Blanks and parasite culture media were ether extracted and analyzed by thin layer chromatography (TLC) in two different solvent systems. Corticosterone production was measured in the culture media by RIA. In some experiments metyrapone (0.1-0.5 mM) was added for 24, 48 or 72 h. Results showed that cysticerci mainly synthesized tritiated 11-deoxy corticosterone (DOC) and small amounts of corticosterone that was also detected by RIA. Small amounts of (3)H-11-deoxy cortisol were also found. Corticosteroid synthesis was time dependent. The addition of metyrapone significantly inhibited tritiated DOC, deoxycortisol and corticosterone synthesis. These results show for the first time that parasites have the capacity to synthesize CS that is modulated by metyrapone. Data suggest that DOC is the main corticosteroid in the parasites. PMID- 22321722 TI - A novel quadripartite dsRNA virus isolated from a phytopathogenic filamentous fungus, Rosellinia necatrix. AB - Here we report the biological and molecular attributes of a novel dsRNA virus isolated from Rosellinia necatrix, a filamentous phytopathogenic fungus. The virus, termed Rosellinia necatrix quadrivirus 1 (RnQV1), forms rigid spherical particles approximately 45 nm in diameter in infected mycelia. The particles contain 4 dsRNA segments, dsRNA1 to dsRNA4, with a size range of 4.9 to 3.7 kbp, each possessing a single large ORF. A comparison of the virus-infected and -cured isogenic fungal strains suggested that RnQV1 infection has no appreciable phenotypic effects. Phylogenetic analysis using the dsRNA3-encoded RdRp sequence revealed that RnQV1 is more distantly related to quadripartite chrysoviruses than to monopartite totiviruses, and is placed in a distinct group from other mycoviruses. No significant sequence similarities were evident between known proteins and RnQV1 structural proteins shown to be encoded by dsRNA2 or dsRNA4. These suggest that RnQV1 is a novel latent virus, belonging to a new family. PMID- 22321723 TI - Qualitative study on perceptions of hand hygiene among hospital staff in a rural teaching hospital in India. AB - BACKGROUND: Hand hygiene is a simple but underutilized measure to control healthcare-associated infections. AIM: To explore staff perceptions of hand hygiene using focus group discussions (FGDs) in a teaching hospital in India. METHODS: Qualitative study. The FGD guide included questions on transmission of infections, hand hygiene practices and problems with implementation, and ways to improve adherence to hand hygiene recommendations. The FGDs were recorded, transcribed verbatim, translated into English (when conducted in Hindi) and analysed using content analysis. FINDINGS: Two themes emerged: 'inter relationship of knowledge, beliefs, motivation, practices and needs' and 'roles and responsibilities for sustainable and efficient implementation of context relevant approaches and interventions'. Staff were generally aware of the importance of hand hygiene for the prevention of healthcare-associated infections, but perceived practical problems with implementation. CONCLUSIONS: The staff suggested various interventions and appeared to be prepared to follow hand hygiene guidelines if the hospital provided the necessary facilities. PMID- 22321724 TI - U.K. laboratory diagnosis of Clostridium difficile infection: in a state of transition, confusion, or both? PMID- 22321725 TI - Clinical and socioeconomic determinants of congenital syphilis in Posadas, Argentina. AB - OBJECTIVES: To explore clinical and socioeconomic factors related to congenital syphilis in Posadas, Argentina. METHODS: Data were collected from 102 mothers who had given birth to an infant with congenital syphilis at Dr. Ramon Madariaga Central Hospital (2005-2007) and 306 control mothers. Clinical and demographic information were collected from clinical records, and socioeconomic details were obtained by interview. Multivariable logistic regression was used to explore the relationships between congenital syphilis and clinical and socioeconomic factors. RESULTS: Receiving the recommended number of prenatal health checks had a clear protective effect on congenital syphilis in the univariate analysis (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.31-0.86), as did being in a stable relationship (OR 0.23, 95% CI 0.14-0.38). Furthermore, women with secondary education or above were over four-times less likely to have a child with congenital syphilis compared to women who had not completed primary school education, even after controlling for the number of prenatal health checks and other factors (adjusted OR 0.24, 95% CI 0.08-0.72). In addition, women with previous stillborn births were over three-times more likely to have a baby with congenital syphilis after controlling for education and prenatal care (adjusted OR 3.37, 95% CI 1.24-9.16). CONCLUSIONS: There is a clear opportunity for reducing the burden of congenital syphilis by promoting syphilis screening and treatment in women with previous stillborn births. In addition, the potential impact of more general policies addressing social determinants of health, such as those improving education, must not be overlooked. PMID- 22321726 TI - The role of second-generation 5-HT3 receptor antagonists in managing chemotherapy induced nausea and vomiting in hematological malignancies. AB - Compared with solid tumor patients, those with hematological malignancies are at particular risk of chemotherapy-induced nausea and vomiting (CINV) because of their young age, exposure to highly-emetogenic induction, consolidation and salvage regimens, the high-dose conditioning regimens used before stem cell transplantation (SCT), and the heavy psychological burden of such treatments. In the absence of prophylaxis, around 75% of patients undergoing SCT experience delayed CINV. With first-generation 5-HT(3) receptor antagonists, only about 20% are completely protected from nausea and vomiting, and this frequent and debilitating adverse event has not been fully addressed. In contrast to solid tumors, there are no internationally agreed guidelines for the prevention and treatment of CINV in hematological malignancies. Work on a consensus is urgently required. The second-generation 5-HT(3) antagonist palonosetron is highly effective in preventing CINV in patients with solid tumors. The extended half life of this agent and its mechanisms of action including allosteric binding, positive cooperativity and 5-HT(3) receptor internalization, may make it particularly effective in controlling delayed CINV. Although controlled comparisons against first-generation 5HT(3) agents have not yet been conducted in the setting of SCT, available evidence suggests that palonosetron may prove beneficial in preventing CINV in high risk patients with hematological malignancies. PMID- 22321727 TI - Inhibition of mitochondrial fission prevents cell cycle progression in lung cancer. AB - Mitochondria exist in dynamic networks that undergo fusion and fission. Mitochondrial fusion and fission are mediated by several GTPases in the outer mitochondrial membrane, notably mitofusin-2 (Mfn-2), which promotes fusion, and dynamin-related protein (Drp-1), which promotes fission. We report that human lung cancer cell lines exhibit an imbalance of Drp-1/Mfn-2 expression, which promotes a state of mitochondrial fission. Lung tumor tissue samples from patients demonstrated a similar increase in Drp-1 and decrease in Mfn-2 when compared to adjacent healthy lung. Complementary approaches to restore mitochondrial network formation in lung cancer cells by overexpression of Mfn-2, Drp-1 inhibition, or Drp-1 knockdown resulted in a marked reduction of cancer cell proliferation and an increase in spontaneous apoptosis. The number of cancer cells in S phase decreased from 32.4 +/- 0.6 to 6.4 +/- 0.3% with Drp-1 inhibition (P<0.001). In a xenotransplantation model, Mfn-2 gene therapy or Drp-1 inhibition could regress tumor growth. The tumor volume decreased from 205.6 +/- 59 to 70.6 +/- 15 mm(3) (P<0.05) with Mfn-2 overexpression and from 186.0 +/- 19 to 87.0 +/- 6 mm(3) (P<0.01) with therapeutic Drp-1 inhibition. Impaired fusion and enhanced fission contribute fundamentally to the proliferation/apoptosis imbalance in cancer and constitute promising novel therapeutic targets. PMID- 22321728 TI - Reconciling the nutritional and glucocorticoid hypotheses of fetal programming. AB - Fetal growth restriction associates with increased risk of adult cardiometabolic and neuropsychiatric disorders. Both maternal malnutrition [notably a low-protein (LP) diet] and stress/glucocorticoid exposure reduce fetal growth and cause persisting abnormalities (programming) in adult offspring. Deficiency of placental 11beta-hydroxysteroid dehydrogenase-2 (11beta-HSD2), which inactivates glucocorticoids, is reduced by an LP diet and has been proposed as a unifying mechanism. Here, we explored the importance of glucocorticoids and placental 11beta-HSD2 in dietary programming. Pregnant mice were fed a control or isocaloric LP diet throughout gestation. The LP diet first elevated fetal glucocorticoid levels, then reduced placental growth, and finally decreased fetal weight near term by 17%. Whereas the LP diet reduced placental 11beta-HSD2 activity near term by ~25%, consistent with previous reports, activity was increased between 20 and 40% at earlier ages, implying that glucocorticoid overexposure in LP fetuses occurs via 11beta-HSD2-independent mechanisms. Consistent with this, heterozygous 11beta-HSD2(+/-) crosses showed that although both LP and 11beta-HSD2 deficiency reduced fetal growth, LP indeed acted independently of 11beta-HSD2. Instead, the LP diet induced the fetal hypothalamic pituitary-adrenal axis per se. Thus, maternal malnutrition and placental 11beta HSD2 deficiency act via distinct processes to retard fetal growth, both involving fetoplacental overexposure to glucocorticoids but from distinct sources. PMID- 22321729 TI - Brain and skin do not contribute to the systemic rise in erythropoietin during acute hypoxia in humans. AB - Erythropoietin (EPO) preserves arterial oxygen content by controlling red blood cell and plasma volumes. Synthesis of EPO was long thought to relate inversely to renal oxygenation, but in knockout mice, brain and skin have been identified as essential for the acute hypoxic EPO response. Whether these findings apply to humans remains unknown. We exposed healthy young subjects to hypoxia (equivalent to 3800 m) and measured EPO in arterial and jugular venous plasma and in cerebrospinal fluid. To examine the role of the skin for EPO production during hypoxia, subjects were exposed to 8 h of hypobaric hypoxia with or without breathing oxygen-enriched air to ensure systemic normoxemia. With 9 h of hypoxia, arterial EPO increased (from 6.0+/-2.2 to 22.0+/-6.0 mU/ml, n=11, P<0.0001) and jugular venous EPO displayed a similar response (to 22.2+/-6.0 mU/ml, n=11). Thus, the arterio-jugular venous EPO difference was unaffected by hypoxia and also in cerebrospinal fluid EPO remained stable following hypoxic exposure (0.33+/-0.15 mU/ml, n=9 in normoxia vs. 0.41+/-0.20 mU/ml, n=9 in hypoxia, P=0.40). No change in plasma EPO was observed when only skin was exposed to hypobaric hypoxia (n=8). Thus, neither dermal oxygen exposure nor cerebral EPO production appears to be important for the systemic EPO response to acute hypoxia in healthy humans. PMID- 22321730 TI - Evaluation of 24-locus MIRU-VNTR in extrapulmonary specimens: study from a tertiary centre in Mumbai. AB - Genotyping of Mycobacterium tuberculosis isolates is a useful tool for epidemiological control of tuberculosis (TB) and phylogenetic exploration of the pathogen. There is a lack of information on the discriminatory power of standard 24-locus mycobacterial interspersed repetitive unit (MIRU) - variable number tandem repeats (VNTR) in India, which has the highest tuberculosis (TB) burden worldwide. Therefore, we assessed its utility on 69 M. tuberculosis (MTB) isolates from patients with extrapulmonary tuberculosis, in comparison to standard insertion sequence (IS) 6110-Restriction fragment length polymorphism (RFLP) fingerprinting and spoligotyping. IS6110-RFLP (HGDI, 0.9987) identified a single cluster of 3 (4.3%) single-copy IS6110 isolates. Spoligotyping showed 69.5% clustering (HGDI, 0.8857). In contrast, MIRU-VNTR analysis identified 69 (100%) unique strains (HGDI, 1.0000). Within the study limits, this observed high discriminatory power suggests that 24-locus MIRU-VNTR genotyping could potentially be used to study long-term transmission of MTB infection in Mumbai. Moreover, high congruence between the MIRU-VNTR-based and spoligotyping-based strain groupings suggests that CAS, EAI and Beijing are the predominant strain lineages in the Mumbai TB patient population. The Beijing lineage isolates were found to be more significantly associated with multi-drug resistance (p < 0.01) than CAS and EAI lineages. PMID- 22321731 TI - Online availability and safety of drugs in shortage: a descriptive study of internet vendor characteristics. AB - BACKGROUND: Unprecedented drug shortages announced by the US Food and Drug Administration (FDA) have severely affected therapeutic access, patient safety, and public health. With continued shortages, patients may seek drugs online. OBJECTIVE: To assess the prevalence of online marketing for current FDA shortage drugs and potential patient safety risks. METHODS: We performed a descriptive study of the prevalence of online marketing for shortage drugs-that is, offers for sale of each drug, including characteristics of online drug sellers and intermediary sites marketing these drugs. RESULTS: Of the 72 FDA shortage-listed drugs, 68 (94%) were offered for sale online. We found 291 offers for these drugs, the vast majority (n = 207, 71.1%) by online drug sellers selling direct to consumers. Intermediary sites included data aggregators (n = 22, 8%), forum links (n = 23, 8%), and personal page data links (n = 34, 12%), as well as Flickr social media links (n = 5, 2%), all advertising drugs without a prescription. Of the 91 online drug sellers identified, 31 (34%) had more than 1 shortage drug offered for sale, representing most (n = 148, 71%) of all online drug seller sales offers. The majority of these online drug sellers (n = 21, 68%) were on the National Association of Boards of Pharmacy (NABP) Not Recommended Sites list. Finally, for shortage drugs with an online drug seller (n = 58, 85%), 53 (91%) had at least one site on the Not Recommended list and 21 (36%) had only sites on the Not Recommended list. CONCLUSIONS: FDA shortage drugs are widely marketed over the Internet. Suspect online drug sellers and intermediaries dominate these sales offers. As a critical risk management issue, patients, providers, and policymakers should be extremely cautious in procuring shortage drugs through Internet sourcing. PMID- 22321732 TI - The pyruvate dehydrogenase complex as a therapeutic target for age-related diseases. AB - Considerable research has been conducted on mitochondrial biology as it pertains to aging. However, relatively little attention has been accorded the pyruvate dehydrogenase complex (PDC) relative to how we grow old and acquire age-related diseases. The purpose of this review is threefold: first, to describe the physiological chemistry of the PDC and define its place in normal cellular bioenergetics; second, to compare and contrast the pathogenesis and clinical features of congenital PDC deficiency with discrete examples of age-associated dysfunction of the complex; and third, to summarize recent findings in Caenorhabditis elegans that shed additional new light on the significance of the PDC to the aging process. PMID- 22321733 TI - Antitumor effects of emodin on LS1034 human colon cancer cells in vitro and in vivo: roles of apoptotic cell death and LS1034 tumor xenografts model. AB - Emodin, an active natural anthraquinone derivative, is found in the roots and rhizomes of numerous Chinese medicinal herbs and exhibits anticancer effects on many types of human cancer cell lines. The aim of this study investigated that emodin induced apoptosis of human colon cancer cells (LS1034) in vitro and inhibited tumor nude mice xenografts bearing LS1034 in vivo. In in vitro study, emodin induced cell morphological changes, decreased the percentage of viability, induced G2/M phase arrest and increased ROS and Ca(2+) productions as well as loss of mitochondrial membrane potential (DeltaPsi(m)) in LS1034 cells. Emodin triggered apoptosis was also confirmed by DAPI staining and these effects are concentration-dependent. Western blot analysis indicated that the protein levels of cytochrome c, caspase-9 and the ratio of Bax/Bcl-2 were increased in LS1034 cells after emodin exposure. Emodin induced the productions of ROS and Ca(2+) release, and altered anti- and pro-apoptotic proteins, leading to mitochondrial dysfunction and activations of caspase-9 and caspase-3 for causing cell apoptosis. In in vivo study, emodin effectively suppressed tumor growth in tumor nude mice xenografts bearing LS1034. Overall, the potent in vitro and in vivo antitumor activities of emodin suggest that it might be developed for treatment of colon cancer in the future. PMID- 22321734 TI - Protective effects of lotus (Nelumbo nucifera Gaertn) germ oil against carbon tetrachloride-induced injury in mice and cultured PC-12 cells. AB - The protective effects of lotus germ oil on liver and kidney damage by carbon tetrachloride-induced chronic hepatotoxicity in mice, PC-12 cells, and DNA damage were investigated. The mice were treated orally with lotus germ oil or dl-alpha tocopherol after administration CCl(4) for 49 consecutive days. The levels of key antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and the concentration of glutathione (GSH), as well as the concentration of malondialdehyde (MDA), an indicator of lipid peroxidation, were determined in homogenates of the liver and the kidney. The pathological histology of the liver was also examined. The activities of SOD, CAT, and the concentration of GSH were increased significantly (p<0.05-0.01) after treated with lotus germ oil in a concentration-dependent manner. Whereas, the content of the peroxidation product MDA were decreased significantly (p<0.05), similar to the serum levels of hepatic enzyme biomarkers (alanine aminotransferase and aspartate aminotransferase). Furthermore, lotus germ oil could inhibit the conversion of super-coiled pBR322 plasmid DNA to the open circular form and apoptosis of hydrogen peroxide-induced PC-12 cells. The result of this study suggested that the lotus germ oil could be recognized as powerful "functional oil" against oxidative stress. PMID- 22321736 TI - Nanogap structures for molecular nanoelectronics. AB - This study is focused on the realization of nanodevices for nano and molecular electronics, based on molecular interactions in a metal-molecule-metal (M-M-M) structure. In an M-M-M system, the electronic function is a property of the structure and can be characterized through I/V measurements. The contact between the metals and the molecule was obtained by gold nanogaps (with a dimension of less than 10 nm), produced with the electromigration technique. The nanogap fabrication was controlled by a custom hardware and the related software system. The studies were carried out through experiments and simulations of organic molecules, in particular oligothiophenes. PMID- 22321737 TI - Toll- and NOD-like receptor mRNA expression in canine sino-nasal aspergillosis and idiopathic lymphoplasmacytic rhinitis. AB - The pathogenesis of canine sino-nasal aspergillosis (SNA) and lymphoplasmacytic rhinitis (LPR) remains poorly understood. The innate immune system is implicated in the etiology of human chronic rhinosinusitis. Therefore, we hypothesized that dysfunction in innate immunity could be implicated in the pathogenesis of SNA and LPR. Expression of messenger RNA (mRNA) encoding Toll-like receptors (TLRs) 1-10 and NOD-like receptors (NODs) 1 and 2 in nasal mucosal biopsies from SNA or LPR dogs was compared with mucosa from healthy controls. Gene expression was quantified using quantitative real-time reverse transcriptase polymerase chain reaction normalized against multiple housekeeper genes. All TLR and NOD genes were quantified in all samples. SNA was associated with significantly increased expression of TLRs 1-4, 6-10; and NOD2, relative to controls. LPR was associated with significantly increased expression of TLRs 1, 2, 6-8, relative to controls. There was significantly more expression of TLRs 1, 4, 6-10 and NOD2 in SNA dogs than in LPR dogs. The significance of these differences in the pathogenesis of these diseases is yet to be determined. PMID- 22321738 TI - Regional and age dependent changes in gene expression of Toll-like receptors and key antimicrobial defence molecules throughout the gastrointestinal tract of dairy calves. AB - The primary aim of this study was to determine regional and age-dependent expression patterns of Toll-like receptors (TLRs), peptidoglycan recognition protein 1 (PGLYRP1), and beta-defensin in rumen, jejunum, ileum, cecum and colon of 3 week (n=8) and 6 month old (n=8) calves. The expression of most TLRs was significantly down-regulated throughout the gastrointestinal tract (GIT) with increasing age. TLR10 expression was significantly higher in ileum than all other gut regions, irrespective of age. TLR2 and TLR4 expression were significantly higher in the cecum and colon of 6 month old calves. Furthermore, expression of beta-defensin, and PGLYRP1 was only detectable in 6 month old calves. The expression of TLRs was positively or negatively correlated with population of total bacteria and/or lactic acid bacteria depending on the GIT region. These observations indicate that innate immune responses to commensal microflora may vary significantly throughout the GIT and with age changes. PMID- 22321739 TI - The pharmacokinetics and pharmacodynamics of rapid-acting insulin analogues and their clinical consequences. AB - Postprandial glucose excursions can inhibit achievement of good glycaemic control, and possibly have a specific effect on the risk of vascular comorbidities. Rapid-acting analogues control these excursions better than human insulin because their pharmacokinetic/pharmacodynamic (PK/PD) profile is closer to that of meal-time endogenous insulin secretion. Review of the findings of PK/PD studies and clinical trials suggests that the three marketed rapid-acting analogues--insulin lispro, insulin aspart and insulin glulisine--are equally efficacious and safe. In comparison with human insulin when using the same basal insulin, they provide comparable glycaemic control with a reduced risk of hypoglycaemia, although the combination of rapid-acting and basal analogues reduces glycated haemoglobin (HbA(1c)) more than human meal-time insulin combined with neutral protamine Hagedorn (NPH) insulin. Some studies have suggested that insulin glulisine has a slightly faster onset of action compared with insulin lispro or insulin aspart, but this has not been translated into demonstrable clinical benefit. Treatment satisfaction in patients with diabetes has been higher when therapy with a rapid-acting analogue is used instead of human insulin, perhaps due to differences in advised timing of injection. The largest benefits in efficacy, hypoglycaemia incidence, treatment satisfaction and quality of life have occurred when patients receive an all-analogue meal-time plus basal regimen as compared with an all-human insulin regimen. No new safety issues have been identified with the marketed rapid-acting analogues, and their insulin-like growth factor 1 receptor affinity and mitogenic activity are comparable to human insulin. PMID- 22321740 TI - Global changes in gene expression by the opportunistic pathogen Burkholderia cenocepacia in response to internalization by murine macrophages. AB - BACKGROUND: Burkholderia cenocepacia is an opportunistic pathogen causing life threatening infections in patients with cystic fibrosis. The bacterium survives within macrophages by interfering with endocytic trafficking and delaying the maturation of the B. cenocepacia-containing phagosome. We hypothesize that B. cenocepacia undergoes changes in gene expression after internalization by macrophages, inducing genes involved in intracellular survival and host adaptation. RESULTS: We examined gene expression by intracellular B. cenocepacia using selective capture of transcribed sequences (SCOTS) combined with microarray analysis. We identified 767 genes with significantly different levels of expression by intracellular bacteria, of which 330 showed increased expression and 437 showed decreased expression. Affected genes represented all aspects of cellular life including information storage and processing, cellular processes and signaling, and metabolism. In general, intracellular gene expression demonstrated a pattern of environmental sensing, bacterial response, and metabolic adaptation to the phagosomal environment. Deletion of various SCOTS identified genes affected bacterial entry into macrophages and intracellular replication. We also show that intracellular B. cenocepacia is cytotoxic towards the macrophage host, and capable of spread to neighboring cells, a role dependent on SCOTS-identified genes. In particular, genes involved in bacterial motility, cobalamin biosynthesis, the type VI secretion system, and membrane modification contributed greatly to macrophage entry and subsequent intracellular behavior of B. cenocepacia. CONCLUSIONS: B. cenocepacia enters macrophages, adapts to the phagosomal environment, replicates within a modified phagosome, and exhibits cytotoxicity towards the host cells. The analysis of the transcriptomic response of intracellular B. cenocepacia reveals that metabolic adaptation to a new niche plays a major role in the survival of B. cenocepacia in macrophages. This adaptive response does not require the expression of any specific virulence associated factor, which is consistent with the opportunistic nature of this microorganism. Further investigation into the remaining SCOTS-identified genes will provide a more complete picture of the adaptive response of B. cenocepacia to the host cell environment. PMID- 22321741 TI - [Correlations between 14-3-3epsilon expression and clinicopathological factors and prognosis in patients with esophageal squamous cell carcinoma]. AB - OBJECTIVE: To investigate the expression of 14-3-3epsilon in esophageal squamous cell carcinoma (ESCC) and relationship of 14-3-3epsilon and clinicopathological factors of ECSS patients. METHODS: The 14-3-3epsilon expression in tumors and adjacent normal epithelia from 72 ESCC patients was detected by immunohistochemical staining. Correlations of 14-3-3epsilon expression or their subcellular localization and clinicopathological factors were analyzed using Chi squared test. Survival curves were generated according to the Kaplan-Meier method, and the statistical analysis was performed by Log-rank test. RESULTS: The expression of 14-3-3epsilon protein was significantly up-regulated in tumors with 77.8% positive and 27.8% strong positive staining, compared with paired adjacent normal epithelia with 43.1% positive and only 2.8% strong positive staining (P < 0.01). In a total of 56 positive staining tumors, 14-3-3epsilon was detected in cytoplasm of 37 (66.1%), in nucleus of 4 (7.1%), in both cytoplasm and nucleus of 15 (26.8%) cases. Whereas, in a total of 31 positive staining normal epithelia, 14-3-3epsilon was detected in cytoplasm of 0, in nucleus of 13 (41.9%), in both cytoplasm and nucleus of 18 (58.1%) cases (P < 0.01). Statistical analysis revealed that strong 14-3-3epsilon expression was correlated with lymph node metastasis (P = 0.028) and lower 5-year survival (P = 0.018). The survival curves calculated by Kaplan-Meier method further showed that the patients with strong 14 3-3epsilon expression had a shorter survival than patients with negative or weak 14-3-3epsilon expression (Log-rank, P = 0.031). No correlation was found between subcellular localization of 14-3-3epsilon in tumor cells and clinicopathologic factors and prognosis of ESCC patients. CONCLUSION: The 14-3-3epsilon expression is significantly up-regulated in ESCCs. It was usually located in cytoplasm of tumor cells, but nucleus of normal epithelia. Strong expression of 14-3-3epsilon in tumors is associated with lymph node metastasis and considered as an poor prognostic factor for ESCC. PMID- 22321742 TI - [Development of a new biliary intraluminal irradiation stent and the primary results of clinical application]. AB - OBJECTIVE: To evaluate the feasibility, safety and efficiency of a new biliary intraluminal irradiation stent system loaded with (125)I seeds. METHODS: The study was approved by the institutional ethics committee of our hospital, and informed consent was obtained from each patient. Patients with malignant biliary obstruction were treated with a new biliary irradiation stent system loaded with (125)I seeds according to a treatment plan system. All of the biliary seeds carrying devices combined with the matched biliary stents were placed by the procedures of percutaneous transhepatic biliary puncture. After stents implantation, all patients were followed-up. RESULTS: The whole biliary stent systems loaded with (125)I seeds were successfully placed in 12 patients, no (125)I seeds exfoliation during the procedure and no radioactive leakage by general emission computed tomography reexamination during the follow-up were observed. The obstructive jaundice relived and the systemic conditions improved remarkably in all patients. There were no complications related to the stents, such as biliary perforation or hemobilia, were observed. And no significant change in the blood routine and immune parameters detected before and after operation during the follow-up were observed. The median survival period was 7.40 months (95%CI 6.204 - 8.596) and the mean survival period was 8.03 months (95%CI 6.142 - 9.909). CONCLUSION: Development of a new biliary intraluminal irradiation stent system loaded with (125)I seeds is technically feasible and safe, treatment of this stent system has potential benefits of extending survival, however the long-term clinical efficacy needs to be certificated by further follow-up observation and control trials. PMID- 22321743 TI - [Adenosine triphosphate-binding gene messenger ribonucleic acid expression in brains of drug-resistant epileptics]. AB - OBJECTIVE: To explore the expression of ATP (adenosine triphosphate)-binding gene mRNA (messenger ribonucleic acid) in brain tissues of patients with drug resistant epilepsy and understand their biological characteristics. METHODS: The postoperative brain tissues were collected randomly from 40 patients with drug refractory epilepsy. Based on the expected results of complementary DNA (cDNA) microarray, reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate ATP-binding gene mRNA expression in brain tissues of 40 patients with drug-resistant epilepsy and 8 normal controls. RESULTS: As compared with 8 normal control cases, the candidate genes of ATP-binding mRNA were higherly expressed in the brain tissues of patients with drug-resistant epilepsy. The rates of Cy5/Cy3 were CDC2L5 2.159, ROCK1 2.538, STCH 2.106, OXSR1 3.791 and ABCB6 2.583 respectively. And the results of RT-PCR corresponded with those of cDNA chip. CONCLUSION: The significant neuronal up-regulation of ATP-binding gene mRNA suggests that abnormal energy metabolism exist in brain tissues of patients with drug-resistant epilepsy. And the apoptosis of neurons and synaptic plasticity caused by abnormal energy metabolism may play an important role in the occurrence and development of patients with drug-resistant epilepsy. PMID- 22321744 TI - [Effects of intraoperative application of radical scavenger edaravone in severe elderly cases]. AB - OBJECTIVE: To observe the effects of intraoperative application of radical scavenger edaravone in severe elderly cases. METHODS: A total of 400 severe elderly patients scheduled for surgery were randomly assigned to receive edaravone 60 mg/40 ml (Group Y) or an equal volume of normal saline (Group C). The arterial blood samples were harvested at immediately after pricking, 1 hour after the beginning of surgery and before saturation to determine the levels of superoxide dismutase (SOD) and malondialdehyde (MDA). The operative duration, fluid volume, blood loss, blood transfusion volume, urine output, intraoperative adverse events, mortality rate, total hospital stay, intensive care unit (ICU) stay, postoperative mechanical ventilation time and complications were recorded. Patients undergoing off-pump coronary artery bypass graft (OPCABG) were evaluated for troponin I (cTnI) and left ventricular ejection fraction (LVEF) before and after 24 hours of surgery. RESULTS: SOD was higher and MDA lower in Group Y than those in Group C at 1 hour intraoperation and before saturation [SOD: (87 +/- 14) U/ml vs (78 +/- 14) U/ml, (83 +/- 13) U/ml vs (77 +/- 14) U/ml, P < 0.01, < 0.05; MDA: (11 +/- 5) nmol/L vs (14 +/- 7) nmol/L, (11 +/- 5) nmol/L vs (14 +/- 6) nmol/L, P < 0.05, < 0.01]. There were more intraoperative hypotension cases requiring a continuous application of vasoactive drugs in Group C (37 cases vs 19 cases), total hospital stay [(21 +/- 9) d vs (23 +/- 9) d, P < 0.05] and ICU stay [(10 +/- 7) d vs (13 +/- 9) d, P < 0.05] were also longer. Postoperative cTnI and LVEF of Group Y significantly improved in OPCABG cases (all P < 0.05). CONCLUSION: The intraoperative application of edaravone in severe elderly patients may prevent MDA increase and SOD decrease and reduce free radical damage. Especially in OPCABG patients, cTnIand LVEF improve significantly. PMID- 22321745 TI - [Relationship of hyperlactatemia and metabolic acidosis]. AB - OBJECTIVE: To investigate the acid-base abnormalities of the patients with hyperlactatemia and explore the relationship of hyperlactatemia and metabolic acidosis so as to seek a more precise index of reflecting organ perfusion. METHODS: From August 2009 to April 2010, all consecutive patients admitted into intensive care unit received an analysis of blood gas. Those individuals with arterial lactate >= 2 mmol/L were selected. RESULTS: In the group of hyperlactatemic patients, the occurrence of metabolic acidosis as judged by the traditional method was less than that by the Stewart's method (33.9% vs 56.0%). No typical acidemia was found. And all components of metabolic acidosis were calculated. Lactate and SIG (strong ion gap) contributed a certain percentage to metabolic acidosis in the survivor and nonsurvivor groups [(33.6 +/- 17.9)% vs (28.6 +/- 23.5)%, (42.1 +/- 18.5)% vs (44.9 +/- 23.0)%]. CONCLUSION: Among the hyperlactatemic patients (Lac >= 2), lactate and unmeasured anions account for most instances of acidosis. These two indicators may offer a more accurate reflection of tissue perfusion. PMID- 22321746 TI - [Early treatment of large soft-tissue wounds with intermittent vacuum sealing drainage]. AB - OBJECTIVE: To evaluate the early clinical efficacy of large soft-tissue wounds with intermittent vacuum sealing drainage. METHODS: From March 2009 to June 2010, the study group was comprised of 56 patients treated with intermittent vacuum sealing drainage. There were 47 males and 9 females with a mean age of 37.5 years (range: 16 - 65). Intermittent vacuum sealing drainage was immediately used after an emergency operation. The mean duration of treatment was 2.5 weeks (range: 1 - 4). The granulation status was observed and wound dressing changed weekly. RESULTS: Among them, all wound surfaces were dry and granulation tissues brightly red. There was no deep infection. The mean healing durations of intermittent and continuous vacuum sealing drainage groups were (32 +/- 4.5) and (37 +/- 7.5) days respectively. And there was no statistical difference (P > 0.05). CONCLUSION: Intermittent vacuum sealing drainage promotes a rapid and copious production of granulation tissue over soft tissue wound. The patient suffering is minimal and the dressings are easy to manage. PMID- 22321747 TI - [Phase I study of anti-EGFR monoclonal antibody (CMAB009) in patients with advanced cancer]. AB - OBJECTIVE: To characterize the safety profiles and serum pharmacokinetic effects of anti-epidermal growth factor receptor monoclonal antibody (CMAB009) in advanced cancer patients and evaluate the preliminary evidence of its anti-tumor activity. METHODS: This phase I, single-center clinical trial had 2 phases of treatment: single-dose phase, followed by a fixed weekly dose. Subjects meeting the inclusion criteria were enrolled. The subjects were randomly assigned to receive 1 of 3 initial doses of CMAB009 (100, 250 & 400 mg/m(2)) for the purpose of single-dose pharmacokinetic evaluation. After a 28-day washout period of allowing for the characterization of pharmacokinetic end points, the eligible patients were permitted to undergo a successive multi-dose phase study. They were divided into 2 dose groups, group A with 4 weekly doses of 250 mg/m(2), group B with the initial dose of 400 mg/m(2), followed by 3 weekly doses of 250 mg/m(2). The subjects were closely monitored for adverse events throughout the trial. RESULTS: A total of 18 subjects were recruited, including colorectal cancer (n = 10), non-small cell lung cancer (n = 7) and gastric cancer (n = 1). CMAB009 associated toxicity was minimal. And the most commonly reported Grade 1/2 adverse events were skin rashes, fever, nausea and headache. Two patients with colorectal cancer achieved partial remission and the time to progression (TTP) was 24 and 16 weeks respectively. CONCLUSION: As a well-tolerated antitumor agent, CMAB009 may be safely administered by the above multi-dosing protocol. PMID- 22321748 TI - [Diagnostic and therapeutic analyses for peritoneal malignant mesothelioma: a report of 26 women]. AB - OBJECTIVE: To investigate the etiology, clinicopathologic features and prognosis of peritoneal malignant mesothelioma (PMM). METHODS: The diagnostic and therapeutic data for PMM from March 2000 to December 2010 were retrospectively analyzed for 26 women. They had an age range of 41 - 78 years old. Among them, 21 patients (81%) had a history of exposure to asbestos. Their major symptoms were abdominal distension, abdominal pain, ascites and abdominopelvic mass. Some had cachexia. Intestinal obstruction occurred in all cases during a late stage. RESULTS: Among them, the tumor marker of CA125 increased markedly in serum and ascitic samples. The positive rate of ascitic cytology was 31%. Type B ultrasound and CT (computed tomography) examinations showed ascites, peritoneal thickening and abdominopelvic mass and pie-shaped omentum. Their general pathological classifications were as follows: diffuse type (n = 23), localized type (n = 3), epithelial (n = 14), sarcoma (n = 3) and mixed type (n = 9). Cytoreductive surgery was performed in 16 cases. Ten patients underwent only laparoscopy while 23 patients received chemotherapy. The comparison of life span was not statistically significant between cytoreductive surgery and laparoscopy (P > 0.05); the difference of life span between <= 6 courses of chemotherapy and < 6 courses was not statistically significant (P > 0.05). CONCLUSION: The history of exposure to asbestos is a risk factor for PMM. PMM with no specific clinical features should be combined with laboratory and imaging studies to make a timely clinical diagnosis. Final diagnosis should be based upon histopathological and immunohistochemical examinations. Surgery and chemotherapy do not prolong the life span of patients. And the patients have a very poor prognosis. PMID- 22321749 TI - [Analysis of related factors of premature delivery for the migrant population in local suburban Beijing areas]. AB - OBJECTIVE: To study the health conditions of pregnant migrant women in some suburban areas of Beijing by comparing a variety of pathological, physiological and social factors and exploring the relevant factors associated with preterm birth so as to prevent effectively preterm birth. METHODS: A total of 279 cases of pregnancy in preterm birth at out hospital from January 2004 to December 2008 were reviewed. The date of maternal age, parity, prenatal examinations, history of vaginitis, history of chorioamnionitis, premature rupture of membranes, occupation, residing location and education status were recorded. And the relationship between them and preterm birth were analyzed by chi(2) test. RESULTS: The overall incidence of preterm birth was 5.34%. And the following factors had statistically significant differences with premature birth: chorioamnionitis, vaginitis, premature rupture of membranes, a lack of prenatal examinations, low education status, migrant population or maternal parity. However there was no statistical significance (P > 0.05) between preterm birth and other factors, such as occupation. CONCLUSION: The incidence of preterm birth is associated with a lack of prenatal examinations, low education status, chorioamnionitis, bacterial vaginitis and premature rupture of membranes. Therefore the migrant women in Beijing should receive targeted education programs during pregnancy. And reproductive tract inflammation should be properly treated. PMID- 22321750 TI - [Interaction of fatty acid oxidation with oxidative stress in preeclampsia-like mouse model at multiple stages of gestation]. AB - OBJECTIVE: To investigate the interactions of fatty acid oxidation with oxidative stress on the preeclampsia (PE)-like development by establishing murine models at multiple stages of gestation. METHODS: Wild-type (WT) mice were injected subcutaneously with nitric oxide synthase (NOS) inhibitor L-arginine methyl ester (L-NAME, 50 mg*kg(-1)*d(-1)) to establish PE-like model (L-NAME group) at early, middle and late pregnant periods respectively. Normal saline (NS group) was injected simultaneously as a control. All groups were divided into subgroups, standard chow group (SC) and high-fat diet group (HF). From Day 1 of pregnancy, all groups were fed simultaneously. ApoE(-/-) pregnant mice were selected as a control group. Identification of mice model and the expressions of mRNA and protein of LCHAD, p47phox, p38MAPK and COX-2 were confirmed by RT-PCR (reverse transcription-polymerase chain reaction) and Western blot respectively. Data were analyzed statistically. RESULTS: The expressions of mRNA and protein of LCHAD significantly decreased in early and middle L-NAME groups in both apoE(-/-) and WT mice (P < 0.05). The expressions of mRNA and protein of LCHAD in the HF groups were lower than the SC groups. The changes were marked in the early HF + L-NAME subgroup in apoE(-/-) mice (P < 0.05). As compared with other groups, the placental expressions of mRNA and protein of p47phox and COX-2 markedly increased in the early and middle L-NAME subgroups in apoE(-/-) mice (P < 0.05), especially in early and middle HF + L-NAME subgroups in apoE(-/-) mice (P < 0.05). ApoE(-/-) mice had a higher expression than that of WT groups (P < 0.05). The expressions of mRNA and protein of p38MAPK showed no differences among all groups. Correlation analysis showed a negative correlation between gene and protein expressions of LCHAD and p47phox, COX-2 (P < 0.05). There was significantly positively correlated between the expression of p47phox, COX-2 and protein (P < 0.05). CONCLUSIONS: The PE-like symptoms have fatty acid oxidation dysfunctions. There is a lower expression of LCHAD. The earlier its onset, the more obvious dysfunctions. In early and middle L-NAME groups, oxidative stress and inflammatory injury occur in both apoE(-/-) and WT mice. A high-fat diet may aggravate the level of oxidative stress especially in PE-like apoE(-/-) murine model. PMID- 22321751 TI - [Effects of the transplantation of adipose-derived stem cell on the expression of Notch1-Dll4 signaling pathway in brain of rats with focal cerebral ischemia]. AB - OBJECTIVE: To investigate the effects of the transplantation of adipose-derived stem cells (ADSC) on the expression of Notch1-Dll4 signaling pathway in brains of rats with focal cerebral ischemia. METHODS: Sixty-five male adult Sprague-Dawley rats were randomly divided into 4 groups: sham-operated group, MCAO (occlusion of middle cerebral artery) group, ADSC-treated group and ADSC & DAPT-treated group. A permanent model of focal cerebral ischemia was established by modified Zea Longa's method. At 24 hours post-MCAO, 1*10(6) DAPT-labeled ADSC were injected into the lateral ventricle of rats in the ADSC-treated group and the same dose of ADSC with DAPT (gamma secretase inhibitor, N-[N-(3,5-difluorophenacetyl)-L alanyl]-S-phenylglycine t-butyl ester) to the rats in the ADSC & DAPT-treated group. Rats are sacrificed at 4, 7, 14 and 28 d post-MCAO. The amount of microvessels was quantified. And the levels of Notch1, Dll4 and Hes1 were detected by Western blot and immunohistochemistry. RESULTS: The density of microvessels significantly increased in the ADSC group (13.93 +/- 0.50, 17.90 +/- 0.62, 20.78 +/- 0.80, 17.28 +/- 1.65) versus the MCAO group (7.03 +/- 0.22, 10.83 +/- 0.63, 16.35 +/- 0.54, 13.80 +/- 2.38) (P < 0.05) and the ADSC + DAPT group (5.73 +/- 0.30, 7.58 +/- 0.52, 7.65 +/- 0.45, 6.48 +/- 1.47) (P < 0.05). And compared with the MCAO group (1.29 +/- 0.07, 2.13 +/- 0.21, 1.92 +/- 0.03) and the ADSC + DAPT group (1.162 +/- 0.099, 1.684 +/- 0.180, 1.041 +/- 0.040), the expressions of Notch1, Dll4 and Hes1 proteins were significantly up-regulated at 14d in the ADSC group (2.52 +/- 0.22, 4.52 +/- 0.36, 2.62 +/- 0.05) (P < 0.05). CONCLUSION: The transplantation of ADSC can improve angiogenesis by up-regulating the post-MCAO expression of Notch1-Dll4 signaling pathway in rats. PMID- 22321752 TI - [Different doses transplanted microglia effect on beta-amyloid protein in rat Alzheimer's models]. AB - OBJECTIVE: To explore the effects of different doses of transplanted microglia (MG) on beta-amyloid protein (Abeta) in rat brain model of Alzheimer's disease (AD). METHODS: A total of 60 SD rats were randomly divided into experimental group and control group. The experimental group was injected with Abeta-42 and the control group saline in hippocampus. At Day 3, different doses of continuously expressed enhanced green fluorescent protein (EGFP) microglial cells cultured in vitro were injected into the rats via carotid artery. At Day 3 post injection, Abeta was labeled by immunofluorescent method. And the expressions of EGFP microglia and Abeta were detected in hippocampus by fluorescence. The relative brain expression of beta-amyloid precursor protein (APP) mRNA was analyzed by RT-PCR (reverse transcription-polymerase chain reaction). RESULTS: The mean fluorescent intensity of EGFP was significantly higher in each experimental group (5.62 +/- 0.61, 8.85 +/- 0.33, 10.24 +/- 0.45, 11.26 +/- 0.37, 12.75 +/- 0.65) than the control group (2.22 +/- 0.32, all P < 0.05); Fluorescent immunohistochemistry showed that the mean fluorescent intensity of Abeta in the 4*10(6) dose group (9.53 +/- 0.23) and the 12*10(6) dose group (8.32 +/- 0.46) were significantly higher than that in the 8*10(6) dose group (4.56 +/- 0.13, both P < 0.05); The fluorescent regions had partial consistence of EGFP and Abeta; RT-PCR (reverse transcription-polymerase chain reaction) results showed that the relative expressions of APP mRNA in the 4*10(6) dose group (1.83 +/- 0.22) and the 12*10(6) dose group (1.94 +/- 0.28) were significantly higher than that in the 8*10(6) dose group (0.43 +/- 0.12, both P < 0.05). CONCLUSION: Abeta has the chemotactic role of MG. MG may swallow Abeta protein partially. But a high dose of MG also accelerates the formation of Abeta. PMID- 22321753 TI - [Modelling of cerebral hyper-perfusion after chronic forebrain ischemia in rats]. AB - OBJECTIVE: To establish the cerebral hyper-perfusion model after chronic forebrain ischemia in rats. METHODS: A total of 72 male rats were equally randomized into 2 modeling groups. The ligation of bilateral common carotid artery could induce chronic forebrain ischemia. And 36 rats were randomly grouped by ischemia duration: control group (n = 9), sham group (n = 9), 2-week ischemia group (n = 9) and 4-week ischemia group (n = 9). The blood flow in frontal lobe was measured at pre- and post-ligation. The neurological score and cerebral infarction area were also compared among the groups. The cerebral reperfusion was concurrently undertaken with an infusion dose of phenylephedrine at 4 ug*kg( 1)*min(-1) via tail vein to produce cerebrally hyperperfused blood flow rate over 200% of baseline following chronic ischemia. According to cerebral hyper perfusion duration, 36 rats were randomly assigned into 4 groups: control group (n = 9), saline infusion group (n = 9), 30-minute cerebral hyper-perfusion group (n = 9) and 2-hour cerebral hyper-perfusion group (n = 9). The blood flow in frontal lobe was measured before and after cerebral hyper-perfusion. The neurological score, blood-brain barrier permeability and dry-wet weight ratio of brain also were compared among the groups. RESULTS: The forebrain blood flow decreased by 67% +/- 2% after the ligation of bilateral common carotid artery. There was significant difference between cerebral hyper-perfusion and saline infusion groups (P < 0.01). No statistic difference was observed in neurological score and cerebral infarction area between 2-week ischemia and control groups. But it was obvious between 4-week ischemia and control groups. The permeability in blood-brain barrier of rats significantly increased in 2-hour hyper-perfusion group (P < 0.05). CONCLUSION: The 2-hour duration of cerebral hyper-perfusion following a 2-week ligation of bilateral common carotid artery may establish a reliable cerebral hyper-perfusion model in rats. PMID- 22321754 TI - [Effects of 5-Aza-2'-deoxycytidine on the carcinogenesis of colorectal cancer in mouse and the in vivo expression of p16/CDKN(2) mRNA]. AB - OBJECTIVE: To explore the effects and relationship of specific demethylation agent 5-Aza-2'-deoxycytidine (5-Aza-CdR) on colorectal cancer (CRC) induced by 1, 2-dimethylhydrazine (DMH) in mouse and the in vivo expression of cyclin-dependent kinases inhibitor p16/CDKN(2) mRNA. METHODS: A total of 40 male KM mice were randomized into 2 groups and CRC was induced by a 22-week injection of DMH. One group was interfered by specific DNA methyltransferase inhibitor 5-Aza-CdR. Another 10 the same source male KM mice were induced by a 22-week injection of saline as none induced cancer control group (negative control group). All mice were sacrificed to examine for colorectal neoplasm. Immunohistochemical staining was used to assess the expression of proliferating cell nuclear antigen (PCNA). The expression of p16/CDKN(2) mRNA was detected by in situ hybridization. RESULTS: The average numbers of neoplasm was higher in the DMH group (7.6 +/- 3.1) than that of the group DMH + 5-Aza-CdR (3.4 +/- 1.8, P < 0.05). Immunohistochemical staining showed there was a significant elevation of PCNA in the group DMH (16/19) as compared with that in the group DMH + 5-Aza-CdR (11/19, P < 0.05). In situ hybridization revealed that the level of tumor suppressor gene p16/CDKN(2) mRNA was significantly lower in the group DMH than that in the group DMH + 5-Aza-CdR. CONCLUSION: The specific demethylation agent 5-Aza-2' deoxycytidine may inhibit the carcinogenesis of CRC. Its mechanism may be related with a high expression of p16/CDKN(2) mRNA. PMID- 22321755 TI - [Effects of exogenous transforming growth factor-beta3 on the activities of its promoter and cAMP-responsive element binding protein-1 in rat hepatic stellate cell]. AB - OBJECTIVE: To explore the effects of exogenous transforming growth factor-beta3 (TGF-beta3) on the activities of its promoter and cAMP-responsive element binding protein-1 (CREB-1) in rat hepatic stellate cell (HSC-T6). METHODS: HSC-T6 was cultured and treated with or without exogenous TGF-beta3 (10 ug/L). Then cell extracts, total RNA and nuclear proteins were collected at different time points. The specimens were detected by luciferase reporter assay, Western blotting and real-time RT-PCR (reverse transcription-polymerase chain reaction) respectively. RESULTS: After treatment, the activity of TGF-beta3 promoter peaked at 24 h (10.68 +/- 0.57 vs 4.83 +/- 0.56, 2.2 folds vs control). And the mutational CRE site completely blocked the activity of TGF-beta3 promoter (0.73 +/- 0.03, P < 0.05). In addition, exogenous TGF-beta3 increased the expression of phospho-CREB 1 in a time-dependent manner. It peaked at 1 h (2.0 folds vs control) and declined slowly. And exogenous TGF-beta3 had no effect on the mRNA and protein expressions of CREB-1 (P > 0.05). CONCLUSION: The activity of TGF-beta3 promoter is up-regulated by exogenous TGF-beta3. And CRE site in TGF-beta3 promoter region is important for the transcription of TGF-beta3 gene in HSC-T6. While activating CREB-1, exogenous TGF-beta3 has no effect on the expressions of CREB-1 protein and mRNA. PMID- 22321756 TI - Antiepileptic drug-induced skin reactions: a retrospective study and analysis in 3793 Chinese patients with epilepsy. AB - OBJECTIVE: To evaluate the incidence and clinical characteristics of AED-related skin reactions, along with factors influencing these reactions, in a sample of 3793 Chinese epileptic patients. MATERIALS AND METHODS: Between February 1999 and April 2010, consecutive patients with epilepsy were studied retrospectively. A detailed survey of each patient's medical records concerning all treatment with AEDs was performed. RESULTS: A total of 3793 (2323 male) Chinese epileptic patients taking at least one AED were investigated. Overall, 137/3793 (3.61%) patients experienced a skin reaction following one out of 11 different of AEDs marketed in China. In this study, we found skin reactions from carbamazepine (CBZ) in 3.80% of exposures, from lamotrigine (LTG) in 11.11%, and from oxcarbazepine (OXC) in 8.92%. Skin reactions developed significantly more often in females than in males (4.97% vs. 2.76%), and a logistic regression analysis confirmed female gender as a factor linked to AED-related rashes (OR=1.84, p<0.001). LTG-induced rashes were more frequent in girls under age 13 than in women over the age of 13 (p<0.05). CONCLUSION: The incidence of skin reactions was somewhat higher for LTG, CBZ, and OXC, whereas valproic acid, levetiracetam, and topiramate were rarely associated with skin reactions. Caution should be exercised when prescribing certain AEDs, particularly CBZ, LTG, and OXC. Females have a higher risk for skin reactions compared to males, though further investigation is needed to discern the underlying mechanisms. PMID- 22321757 TI - Topiramate and erectile dysfunction: Pathogenic mechanisms beyond sexual hormonal changes! PMID- 22321758 TI - Effectiveness of home rehabilitation program for ischemic stroke upon disability and quality of life: a randomized controlled trial. AB - BACKGROUND: To develop and examine the effectiveness of individual 6-month home rehabilitation program in ischemic stroke patients upon disability and quality of life at 2 years. METHODS: This is a prospective randomized controlled trial (RCT) in 60 patients with recent ischemic stroke. They were randomly assigned to receive either home rehabilitation program once a month for 6 months with audiovisual materials (intervention group) or usual care (control group). We collected outcome data after discharge from the hospital until 2 years. The Barthel index (BI), the modified Rankin Scale (mRS) and utility index (EQ-5D) were measured for function, disability and quality of life respectively. RESULTS: At 2 years, the BI was significantly improved in the intervention group more than the control group: 97.2+/-2.8 vs. 76.4+/-9.4, p<0.001. The good outcome, defined as BI 95-100, or mRS 0 or 1. For BI, there were 29 patients (96.7%) in intervention group vs 12 patients (42.9%) in usual care group (95% CI, 42.0, 85.0, p=0.03). For mRS, there were 28 patients (93.3%) in intervention group vs 9 patients (32.1%) in usual care group (95% CI, 38.2, 87.0, p=0.02). Number needed to treat for good outcome in mRS was 2.0 (95% CI: 1.0, 1.3). The mean (SD) of utility index in intervention group and control group were 0.9+/-0.02 and 0.7+/ 0.04 respectively (p=0.03). There was no significant interaction in baseline characteristics and treatment outcome. CONCLUSIONS: Early home rehabilitation program in the first 6 months period after ischemic stroke leads to more rapid improvement in function, reducing disability and increase quality of life than usual care. PMID- 22321759 TI - Impact of enrofloxacin on the human intestinal microbiota revealed by comparative molecular analysis. AB - The indigenous human intestinal microbiota could be disrupted by residues of antibiotics in foods as well as therapeutically administered antibiotics to humans. These disruptions may lead to adverse health outcomes. To observe the possible impact of residues of antibiotics at concentrations below therapeutic levels on human intestinal microbiota, we performed studies using in vitro cultures of fecal suspensions from three individuals with 10 different concentrations (0, 0.1, 0.5, 1, 5, 10, 15, 25, 50 and 150 MUg/ml) of the fluoroquinolone, enrofloxacin. The bacterial communities of the control and enrofloxacin dosed fecal samples were analyzed by denaturing gradient gel electrophoresis (DGGE) and pyrosequencing. In addition, changes of functional gene expression were analyzed by a pyrosequencing-based random whole-community mRNA sequencing method. Although each individual had a unique microbial composition, the communities of all individuals were affected by enrofloxacin. The proportions of two phyla, namely, Bacteroidetes and Proteobacteria, were significantly reduced with increasing concentrations of enrofloxacin exposure, while the proportion of Firmicutes increased. Principal Coordinate Analysis (PCoA) using the Fast UniFrac indicated that the community structures of intestinal microbiota were shifted by enrofloxacin. Most of the mRNA transcripts and the anti-microbial drug resistance genes increased with increasing concentrations of enrofloxacin. 16S rRNA gene pyrosequencing of control and enrofloxacin treated fecal suspensions provided valuable information of affected bacterial taxa down to the species level, and the community transcriptomic analyses using mRNA revealed the functional gene expression responses of the changed bacterial communities by enrofloxacin. PMID- 22321761 TI - Folate status and health behaviours in two Australian Indigenous populations in north Queensland. AB - OBJECTIVE: To assess nutritional status using red-cell folate (RCF) and associated health behaviours including fruit and vegetable intake, smoking, drinking and physical activity in two Indigenous populations living in remote northern Australia. DESIGN: A cross-sectional survey conducted during 1998-2000. SETTING: Twenty-six rural communities in north Queensland, Australia. SUBJECTS: A total of 2524 Indigenous people aged 15 years and over was included in the study. Self-reported fruit and vegetable intake, tobacco smoking, alcohol intake and physical activity were recorded. RCF was measured using the Bayer Advia Centaur automated immunoassay system. The association between low RCF (RCF<295 nmol/l) and risk factors was analysed using general linear models adjusted for demographic factors and covariates, namely BMI, diabetes and dyslipidaemia. RESULTS: The prevalence of RCF deficiency was higher in Aboriginal participants compared with Torres Strait Islanders (25.6 % v. 14.8 %, P < 0.001). Young women of childbearing age were more likely to have low RCF. Among Aboriginal adults, smoking was strongly associated with low RCF (risk ratio = 1.9, 95 % CI 1.5, 2.5 in females and risk ratio = 2.9, 95 % CI 1.9, 4.2 in males). CONCLUSIONS: Indigenous Australians, especially women of childbearing age, had high prevalence of low RCF. Smoking was associated with insufficient folate independent of fruit and vegetable intake and alcohol consumption in the Aboriginal population. This population with an already higher risk of obesity and higher rate of tobacco smoking should be targeted to improve nutrition status to prevent ill health such as diabetes and CVD. PMID- 22321760 TI - Renin-angiotensin inhibition in systolic heart failure and chronic kidney disease. AB - BACKGROUND: The role of renin-angiotensin inhibition in older patients with systolic heart failure with chronic kidney disease remains unclear. METHODS: Of the 1665 patients (aged>=65 years) with systolic heart failure (ejection fraction<45%) and chronic kidney disease (estimated glomerular filtration rate<60 mL/min/1.73 m(2)), 1046 received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Propensity scores for the receipt of these drugs, estimated for each of the 1665 patients, were used to assemble a matched cohort of 444 pairs of patients receiving and not receiving these drugs who were balanced on 56 baseline characteristics. RESULTS: During more than 8 years of follow-up, all-cause mortality occurred in 75% and 79% of matched patients with chronic kidney disease receiving and not receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, respectively (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.74-0.996; P=.045). There was no significant association with heart failure hospitalization (HR, 0.86; 95% CI, 0.72-1.03; P=.094). Similar mortality reduction (HR, 0.83; 95% CI, 0.70-1.00; P=.046) occurred in a subgroup of matched patients with estimated glomerular filtration rate less than 45 mL/min/1.73 m(2). Among 171 pairs of propensity-matched patients without chronic kidney disease, the use of these drugs was associated with a significant reduction in all-cause mortality (HR, 0.72; 95% CI, 0.55-0.94; P=.015) and heart failure hospitalization (HR, 0.71; 95% CI, 0.52-0.95; P=.023). CONCLUSION: Discharge prescription of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant modest reduction in all-cause mortality in older patients with systolic heart failure with chronic kidney disease, including those with more advanced chronic kidney disease. PMID- 22321762 TI - Population genetic data for 11 X-STR loci in eleven populations of India. AB - Allele frequencies and forensic parameters were estimated for 11 X chromosome STRs (DXS9898, DXS7424, DXS981, DXS8377, DXS9895, DXS10161, DXS10164, DXS6800, DXS6801, DXS9902 and DXS7423) from 749 samples of unrelated male individuals belonging to eleven populations of India. PMID- 22321764 TI - Intra-event variability of Escherichia coli and total suspended solids in urban stormwater runoff. AB - Sediment levels are important for environmental health risk assessments of surface water bodies, while faecal pollution can introduce significant public health risks for users of these systems. Urban stormwater is one of the largest sources of contaminants to surface waters, yet the fate and transport of these contaminants (especially those microbiological) have received little attention in the literature. Stormwater runoff from five urbanized catchments were monitored for pathogen indicator bacteria and total suspended solids in two developed countries. Multiple discrete samples were collected during each storm event, allowing an analysis of intra-event characteristics such as initial concentration, peak concentration, maximum rate of change, and relative confidence interval. The data suggest that a catchment's area influences pollutant characteristics, as larger catchments have more complex stormwater infrastructure and more variable pollutant sources. The variability of total suspended solids for many characteristics was similar to Escherichia coli, indicating that the variability of E. coli may not be substantially higher than that of other pollutants as initially speculated. Further, variations in E. coli appeared to be more commonly correlated to antecedent climate, while total suspended solids were more highly correlated to rainfall/runoff characteristics. This emphasizes the importance of climate on microbial persistence and die off in urban systems. Discrete intra-event concentrations of total suspended solids and, to a lesser extent E. coli, were correlated to flow, velocity, and rainfall intensity (adjusted by time of concentrations). Concentration changes were found to be best described by adjusted rainfall intensity, as shown by other researchers. This study has resulted in an increased understanding of the magnitude of intra-event variations of total suspended solids and E. coli and what physical and climatic parameters influence these variations. PMID- 22321763 TI - Ion and solute transport by Prestin in Drosophila and Anopheles. AB - The gut and Malpighian tubules of insects are the primary sites of active solute and water transport for controlling hemolymph and urine composition, pH, and osmolarity. These processes depend on ATPase (pumps), channels and solute carriers (Slc proteins). Maturation of genomic databases enables us to identify the putative molecular players for these processes. Anion transporters of the Slc4 family, AE1 and NDAE1, have been reported as HCO(3)(-) transporters, but are only part of the story. Here we report Dipteran (Drosophila melanogaster (d) and Anopheles gambiae (Ag)) anion exchangers, belonging to the Slc26 family, which are multi-functional anion exchangers. One Drosophila and two Ag homologues of mammalian Slc26a5 (Prestin) and Slc26a6 (aka, PAT1, CFEX) were identified and designated dPrestin, AgPrestinA and AgPrestinB. dPrestin and AgPrestinB show electrogenic anion exchange (Cl(-)/nHCO(3)(-), Cl(-)/SO(4)(2-) and Cl( )/oxalate(2-)) in an oocyte expression system. Since these transporters are the only Dipteran Slc26 proteins whose transport is similar to mammalian Slc26a6, we submit that Dipteran Prestin are functional and even molecular orthologues of mammalian Slc26a6. OSR1 kinase increases dPrestin ion transport, implying another set of physiological processes controlled by WNK/SPAK signaling in epithelia. All of these mRNAs are highly expressed in the gut and Malpighian tubules. Dipteran Prestin proteins appear suited for central roles in bicarbonate, sulfate and oxalate metabolism including generating the high pH conditions measured in the Dipteran midgut lumen. Finally, we present and discuss Drosophila genetic models that integrate these processes. PMID- 22321765 TI - Sun protection--do we know enough? AB - INTRODUCTION: Sun protection, particularly the appropriate use of sunscreens is an important modifiable risk factor in the prevention of skin cancers. Our aim was to assess the current knowledge levels regarding sun protection, across plastic surgeons in the UK. METHODS: A 12-point questionnaire based on the points contained in the patient information packs on sun protection produced by the British Association of Dermatology was circulated electronically amongst 551 BAPRAS members. We received 73 responses (13.3%). Questions were formulated around the basic information patients would expect to receive from a skin cancer specialist at the time of the diagnosis. RESULTS: On average, participants could answer only 52.4% of the questions correctly. Only 9.7% (95% CI 3-17) of participants could accurately quantify the role of UV exposure in causation of melanoma. A total of 37.5% correctly identified the duration of action of sunscreen to be 3-4 h. Half of the participants were not aware that geographical conditions like altitude and latitude, as well as shade, could alter sun protection. A similar number could not answer questions related to the protective action of clothing. CONCLUSION: As principal stakeholders in the treatment and outcomes of skin cancer patients, plastic surgeons could be at the forefront of influencing patients' behaviour regarding sun protection measures. The results demonstrate a need for better awareness and education regarding the knowledge of sunscreens and UV protection. Improved education would lead to health benefits for patients and their relatives and influence the primary prevention of this enlarging health issue of skin cancer. PMID- 22321766 TI - Inferior alveolar nerve reconstruction with interpositional sural nerve graft: a sensible addition to one-stage mandibular reconstruction. AB - BACKGROUND: This study was to evaluate the sensory recovery in the lower lip and chin in patients who underwent segmental mandibulectomy involving inferior alveolar nerve and simultaneous reconstruction with fibular osteoseptocutaneous flap and interposition sural nerve graft. MATERIAL AND METHOD: From 1993 to 2004, a total of 20 patients underwent segmental mandibulectomy, simultaneous fibula osteoseptocutaneous flap reconstruction and interpositional sural nerve graft. Twelve patients were available for the study. There were seven male and five female patients with average age of 35.8 years (16-52 years). The sense at the lower lip and chin was measured by two-point discrimination both at the operated and non-operated side at an average of 64.3 months (12-146 months). RESULT: The operated side revealed an average of 13.7 mm for static (STPD) and 13.3 mm for moving two-point discrimination (MTPD) at the lower lip and 13.7 mm for static and 13.4 mm for MTPD at the chin. Data from the non-operated side averaged 3.4 mm for static and 3.2 mm for MTPD at lower lip and 5.1 mm for static and 4.5 mm for moving discrimination at the chin. All patients recovered better than protective sensation on the operated side, which was sufficient to prevent self-mutilation, preserve comprehensible speech and maintain oral competence. No patient complained of significant donor site morbidity. CONCLUSION: Simultaneous reconstruction of a segmental mandibulectomy involving inferior alveolar nerve with a fibula osteoseptocutaneous flap and interpositional sural nerve graft offers simultaneous replacement of mandibular architecture and restoration of protective perioral sensation. PMID- 22321767 TI - Serial measurements of cardiac biomarkers in patients after allogeneic hematopoietic stem cell transplantation. AB - BACKGROUND: Previous therapy with anthracyclines (ANT) and conditioning regimen followed by hematopoietic stem cell transplantation (HSCT) represents a high risk for development of cardiotoxicity. The aim of this study was to assess subclinical myocardial damage after HSCT using echocardiography and cardiac biomarkers--high sensitive cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and to identify patients at risk of developing clinical cardiotoxicity. PATIENTS AND METHODS: Thirty-seven patients who were treated with allogeneic HSCT for hematologic diseases at median age of 28 years at time of HSCT were studied. Conditioning regimen included either chemotherapy without total body irradiation (TBI) or combination of chemotherapy with TBI. Twenty-nine (78.3%) patients were pretreated with ANT therapy. Cardiac biomarkers were serially measured before conditioning regimen and at days 1, 14 and 30 after HSCT. Cardiac systolic and diastolic functions were assessed before conditioning regimen and 1 month after HSCT by echocardiography. RESULTS: The changes in plasma NT-proBNP and hs-cTnT levels during the 30 days following the HSCT were statistically significant (P < 0.01 v.s. P < 0.01). Persistent elevations of NT proBNP and hs-cTnT simultaneously for a period exceeding 14 days after HSCT were found in 29.7% patients. Serum concentrations of cardiomarkers were significantly elevated in ANT group compared to non-ANT group. These observations were underscored by the echocardiographic studies which did reveal significant changes in systolic and diastolic parameters. Five of 37 (13.5%) patients developed clinical manifestation of cardiotoxicity. CONCLUSIONS: Elevations in both cardiac biomarkers were found before clinical signs of cardiotoxicity developed. Persistent elevations in NT-pro-BNP and hs-cTnT concentrations simultaneously for a period exceeding 14 days might be used for identification of patients at risk of developing cardiotoxicity and requiring further cardiological follow up. PMID- 22321768 TI - Hot topics in epigenetic mechanisms of aging: 2011. AB - Aging is a complex process that results in compromised biological functions of the organism and increased susceptibility to disease and death. Although the molecular basis of aging is currently being investigated in many experimental contexts, there is no consensus theory to fully explain the aging process. Epigenetic factors, including DNA methylation, histone modifications, and microRNA expression, may play central roles in controlling changes in gene expression and genomic instability during aging. In this Hot Topic review, we first examine the mechanisms by which these epigenetic factors contribute to aging in diverse eukaryotic species including experimental models of yeasts, worms, and mammals. In a second section, we will emphasize in the mammalian epigenetic alterations and how they may affect human longevity by altering stem cell function and/or somatic cell decline. The field of aging epigenetics is ripe with potential, but is still in its infancy, as new layers of complexity are emerging in the epigenetic network. As an example, we are only beginning to understand the relevance of non-coding genome to organism aging or the existence of an epigenetic memory with transgenerational inheritance. Addressing these topics will be fundamental for exploiting epigenetics phenomena as markers of aging-related diseases or as therapeutic targets. PMID- 22321769 TI - Rate of amino acid substitution is influenced by the degree and conservation of male-biased transcription over 50 myr of Drosophila evolution. AB - Sex-biased gene expression (i.e., the differential expression of genes between males and females) is common among sexually reproducing species. However, genes often differ in their sex-bias classification or degree of sex bias between species. There is also an unequal distribution of sex-biased genes (especially male-biased genes) between the X chromosome and the autosomes. We used whole genome expression data and evolutionary rate estimates for two different Drosophilid lineages, melanogaster and obscura, spanning an evolutionary time scale of around 50 Myr to investigate the influence of sex-biased gene expression and chromosomal location on the rate of molecular evolution. In both lineages, the rate of protein evolution correlated positively with the male/female expression ratio. Genes with highly male-biased expression, genes expressed specifically in male reproductive tissues, and genes with conserved male-biased expression over long evolutionary time scales showed the fastest rates of evolution. An analysis of sex-biased gene evolution in both lineages revealed evidence for a "fast-X" effect in which the rate of evolution was greater for X linked than for autosomal genes. This pattern was particularly pronounced for male-biased genes. Genes located on the obscura "neo-X" chromosome, which originated from a recent X-autosome fusion, showed rates of evolution that were intermediate between genes located on the ancestral X-chromosome and the autosomes. This suggests that the shift to X-linkage led to an increase in the rate of molecular evolution. PMID- 22321771 TI - Progress with a difficult infection. PMID- 22321770 TI - Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. AB - BACKGROUND: Infection with Clostridium difficile is the primary infective cause of antibiotic-associated diarrhoea. We aimed to compare efficacy and safety of fidaxomicin and vancomycin to treat patients with C difficile infection in Europe, Canada, and the USA. METHODS: In this multicentre, double-blind, randomised, non-inferiority trial, we enrolled patients from 45 sites in Europe and 41 sites in the USA and Canada between April 19, 2007, and Dec 11, 2009. Eligible patients were aged 16 years or older with acute, toxin-positive C difficile infection. Patients were randomly allocated (1:1) to receive oral fidaxomicin (200 mg every 12 h) or oral vancomycin (125 mg every 6 h) for 10 days. The primary endpoint was clinical cure, defined as resolution of diarrhoea and no further need for treatment. An interactive voice-response system and computer-generated randomisation schedule gave a randomisation number and medication kit number for each patient. Participants and investigators were masked to treatment allocation. Non-inferiority was prespecified with a margin of 10%. Modified intention-to-treat and per-protocol populations were analysed. This study is registered with ClinicalTrials.gov, number NCT00468728. FINDINGS: Of 535 patients enrolled, 270 were assigned fidaxomicin and 265 vancomycin. After 26 patients were excluded, 509 were included in the modified intention-to-treat (mITT) population. 198 (91.7%) of 216 patients in the per-protocol population given fidaxomicin achieved clinical cure, compared with 213 (90.6%) of 235 given vancomycin, meeting the criterion for non-inferiority (one-sided 97.5% CI -4.3%). Non-inferiority was also shown for clinical cure in the mITT population, with 221 (87.7%) of 252 patients given fidaxomicin and 223 (86.8%) of 257 given vancomycin cured (one-sided 97.5% CI -4.9%). In most subgroup analyses of the primary endpoint in the mITT population, outcomes in the two treatment groups did not differ significantly; although patients receiving concomitant antibiotics for other infections had a higher cure rate with fidaxomicin (46 [90.2%] of 51) than with vancomycin (33 [73.3%] of 45; p=0.031). Occurrence of treatment-emergent adverse events did not differ between groups. 20 (7.6%) of 264 patients given at least one dose of fidaxomicin and 17 (6.5%) of 260 given vancomycin died. INTERPRETATION: Fidaxomicin could be an alternative treatment for infection with C difficile, with similar efficacy and safety to vancomycin. FUNDING: Optimer Pharmaceuticals. PMID- 22321772 TI - Gait control: a specific subdomain of executive function? AB - BACKGROUND: Few studies looked at the association between gait variability and executive subdomains (ESD). The aim of this study was to examine the association between ESD (i.e., information updating and monitoring) and stride time variability among healthy older adults. METHODS: Seventy-eight healthy older adults (mean age 69.9 +/- 0.9 years, 59% women) were divided into 3 groups according to stride time variability (STV) tertiles while steady state walking. Coefficient of variation of stride time was used as a marker of STV. Scores on cognitive tests evaluating information updating and monitoring (Digit Span test), mental shifting (Trail Making Test part A and part B) and cognitive inhibition (Stroop Color Word test) were used as measures of ESD. RESULTS: The full adjusted and the stepwise backward logistic regression models showed that the highest tertile (i.e., the worst performance) of STV was only associated with lower Digit Span performance (Odds ratio = 0.78 with P = 0.020 and Odds ratio = 0.81 with P = 0.019). CONCLUSIONS: Information updating and monitoring are associated with STV in the sample of studied participants, suggesting that walking may be a complex motor task depending specifically of this subdomain of executive functions. PMID- 22321773 TI - Transcriptome profiling of low temperature-treated cassava apical shoots showed dynamic responses of tropical plant to cold stress. AB - BACKGROUND: Cassava is an important tropical root crop adapted to a wide range of environmental stimuli such as drought and acid soils. Nevertheless, it is an extremely cold-sensitive tropical species. Thus far, there is limited information about gene regulation and signalling pathways related to the cold stress response in cassava. The development of microarray technology has accelerated the study of global transcription profiling under certain conditions. RESULTS: A 60-mer oligonucleotide microarray representing 20,840 genes was used to perform transcriptome profiling in apical shoots of cassava subjected to cold at 7 degrees C for 0, 4 and 9 h. A total of 508 transcripts were identified as early cold-responsive genes in which 319 sequences had functional descriptions when aligned with Arabidopsis proteins. Gene ontology annotation analysis identified many cold-relevant categories, including 'Response to abiotic and biotic stimulus', 'Response to stress', 'Transcription factor activity', and 'Chloroplast'. Various stress-associated genes with a wide range of biological functions were found, such as signal transduction components (e.g., MAP kinase 4), transcription factors (TFs, e.g., RAP2.11), and reactive oxygen species (ROS) scavenging enzymes (e.g., catalase 2), as well as photosynthesis-related genes (e.g., PsaL). Seventeen major TF families including many well-studied members (e.g., AP2-EREBP) were also involved in the early response to cold stress. Meanwhile, KEGG pathway analysis uncovered many important pathways, such as 'Plant hormone signal transduction' and 'Starch and sucrose metabolism'. Furthermore, the expression changes of 32 genes under cold and other abiotic stress conditions were validated by real-time RT-PCR. Importantly, most of the tested stress-responsive genes were primarily expressed in mature leaves, stem cambia, and fibrous roots rather than apical buds and young leaves. As a response to cold stress in cassava, an increase in transcripts and enzyme activities of ROS scavenging genes and the accumulation of total soluble sugars (including sucrose and glucose) were also detected. CONCLUSIONS: The dynamic expression changes reflect the integrative controlling and transcriptome regulation of the networks in the cold stress response of cassava. The biological processes involved in the signal perception and physiological response might shed light on the molecular mechanisms related to cold tolerance in tropical plants and provide useful candidate genes for genetic improvement. PMID- 22321774 TI - Psychometric validation of a knowledge questionnaire on micronutrients among adolescents and its relationship to micronutrient status of 15-19-year-old adolescent boys, Hyderabad, India. AB - OBJECTIVE: To develop a psychometrically valid questionnaire for testing knowledge on micronutrients and to assess the relationship between knowledge and biomarkers of micronutrient status among adolescents. DESIGN: Cross-sectional, institution-based, validity and reliability study. SETTING: Seven higher secondary schools were covered in the limits of Greater Hyderabad Municipal Corporation, Hyderabad, India. SUBJECTS: Students aged 15-19 years, n 92 for the pre-test, n 108 for test-retest and n 109 for studying the relationship between knowledge and biomarkers of Fe, retinol, ascorbic acid, alpha-tocopherol, folic acid and vitamin B12 status. RESULTS: From an item pool of 106, thirty-one items were selected based on content validity. Statistical tools to obtain a valid and reliable questionnaire among adolescent boys and girls resulted in eighteen items with a difficulty index of 0.11-0.86, discrimination index of 0.20-0.72 and validity index (point bi-serial correlation) of 0.10-0.62. Reliability as measured by Cronbach's alpha was 0.71 and the intra-class correlation coefficient was 0.80. A Bland-Altman plot showed good agreement between test and retest scores. The mean response score to the eighteen-item questionnaire was 5.2 (sd 2.68). The mean values of serum retinol were significantly different (P = 0.022) between groups below (24.8 (sd 6.64) MUg/dl) and above (28.0 (sd 7.67) MUg/dl) the 50th percentile of knowledge score. The relationship persisted after controlling for economic status as a covariate using analysis of covariance (P = 0.018). Other micronutrients did not show any significant relationship. CONCLUSIONS: A valid and reliable eighteen-item knowledge questionnaire was constructed and found to have a significant positive relationship with plasma retinol status alone. PMID- 22321775 TI - Alternative splicing interference by xenobiotics. AB - The protein coding sequence of most eukaryotic genes (exons) is interrupted by non-coding parts (introns), which are excised in a process termed splicing. To generate a mature messenger RNA (mRNA) hundreds of combinatorial protein-protein and RNA-protein interactions are required to splice out often very large introns with high fidelity and accuracy. Inherent to splicing is the use of alternative splice sites generating immense proteomic diversity from a limited number of genes. In humans, alternative splicing is a major mode of regulating gene expression, occurs in over 90% of genes and is particularly abundant in the brain. Only recently, it has been recognized that the complexity of the splicing process makes it susceptible to interference by various xenobiotics. These compounds include antineoplastic substances, commonly used drugs and food supplements and cause a spectrum of effects ranging from deleterious inhibition of general splicing to highly specific modifications of alternative splicing affecting only certain genes. Alterations in splicing have been implicated in numerous diseases such as cancer and neurodegeneration. Splicing regulation plays an important role in the execution of programmed cell death. The switch between anti- and pro-apoptotic isoforms by alternative splice site selection and misregulation of a number of splicing factors impacts on cell survival and disease. Here, our current knowledge is summarized on compounds interfering with general and alternative splicing and of the current methodology to study changes in these processes relevant to the field of toxicology and future risk assessments. PMID- 22321776 TI - Metabolic outcomes of matched patient populations initiating exenatide BID vs. insulin glargine in an ambulatory care setting. AB - AIM: This observational study evaluated the clinical effectiveness of exenatide BID (exenatide) vs. insulin glargine (glargine) in patients with type 2 diabetes mellitus in ambulatory clinical practice. METHODS: Retrospective analyses were conducted using an electronic medical record (EMR) database among adult patients with type 2 diabetes mellitus initiating exenatide or glargine between 1 November 2006 and 30 April 2009. The cohorts were propensity-score matched to control baseline demographics, clinical measures, health status and medication use. The changes from baseline to a 12-month follow-up period for A1C (primary outcome), weight, body mass index (BMI), blood pressure and lipid levels were compared between the matched cohorts using paired tests. RESULTS: Propensity-score matching between the exenatide (n = 4494) and glargine (n = 5424) cohorts led to 2683 matched pairs with comparable characteristics, including age, gender and baseline clinical values. The exenatide cohort achieved a greater mean reduction in A1C (-0.6% vs. -0.4%, p < 0.01), weight (-2.6 kg vs. -0.2 kg, p < 0.01), BMI ( 0.8 kg/m(2) vs. -0.04 kg/m(2) , p < 0.01) and systolic blood pressure (SBP) (-1.8 mmHg vs. -0.1 mmHg, p < 0.01) in the follow-up period. The changes in diastolic blood pressure and lipid levels were not significantly different between cohorts. CONCLUSIONS: Compared to glargine, exenatide-treated patients experienced significant reductions in A1C, weight, BMI and SBP. Acknowledging the limitations of observational research, exenatide showed greater clinical effectiveness than glargine from a large EMR database in the ambulatory care setting. PMID- 22321777 TI - Comment on: "A promoter polymorphism (rs17222919, -1316T/G) of ALOX5AP is associated with intracerebral hemorrhage in Korean population" by Hwan Kim D. et al. [Prostaglandins Leukot. Essent. Fatty Acids 85 (2011) 115-120]. PMID- 22321778 TI - Synthesis, biological evaluation, and structure-activity relationship of clonazepam, meclonazepam, and 1,4-benzodiazepine compounds with schistosomicidal activity. AB - The inherent morbidity and mortality caused by schistosomiasis is a serious public health problem in developing countries. Praziquantel is the only drug in therapeutic use, leading to a permanent risk of parasite resistance. In search for new schistosomicidal drugs, meclonazepam, the 3-methyl-derivative of clonazepam, is still considered an interesting lead-candidate because it has a proven schistosomicidal effect in humans but adverse effects on the central nervous system did not allow its clinical use. Herein, the synthesis, in vitro biological evaluation, and molecular modeling of clonazepam, meclonazepam, and analogues are reported to establish the first structure-activity relationship for schistosomicidal benzodiazepines. Our findings indicate that the amide moiety [N(1) H-C(2) (=O)] is the principal pharmacophoric unit of 1,4-benzodiazepine schistosomicidal compounds and that substitution on the amide nitrogen atom (N(1) position) is not tolerated. PMID- 22321779 TI - [Discerning the trends, establishing the strategy, refining the culture, creating a new situation for the development of respiratory medicine in China]. PMID- 22321780 TI - [Prognostic values for in-hospital event rate of early E/Em in patients with acute myocardial infarction]. AB - OBJECTIVE: To assess the prognostic values for in-hospital event rate of tissue Doppler imaging (TDI) parameter (E/Em) after acute myocardial infarction. METHODS: A total of 289 patients with acute myocardial infarction were retrospectively examined. Their clinical data and echocardiograms were obtained. Clinical events were recorded. Patients were divided into two groups according to the value of ratio of early transmitral flow velocity to early diastolic velocity of mitral annulus (E/Em): Group E/Em < 10 (n = 152) and Group E/Em >= 10 (n = 137). Clinical characteristics, echocardiographic parameters and the rate of cardiac events were compared. Predictors of heart failure were identified by multivariate Logistic regression analysis. RESULTS: On echocardiography, the patients with an E/Em ratio >= 10 had statistically larger left atrial diameter [(39.1 +/- 6.2) vs (36.0 +/- 4.4) mm, P = 0.000] and left ventricular end diastolic diameter [(52.3 +/- 7.3)vs (49.2 +/- 5.2) mm, P = 0.000]. Worse systolic functions were found in group E/Em >= 10: left ventricular ejection fraction (LVEF) [(48.3 +/- 11.7)% vs (56.7 +/- 9.7)%, P = 0.000]. Systolic velocities of mitral annulus (Sm) [(6.6 +/- 1.7) vs (8.6 +/- 2.2) cm/s, P = 0.000]. Em [(6.4 +/- 1.9) vs (9.4 +/- 2.4) cm/s, P = 0.000] was statistically lower than that of E/Em < 10 group. Killip classes on admission were statistically higher in group E/Em >= 10 than those of the other group [(1.7 +/- 0.9) vs (1.2 +/- 0.6), P = 0.000]. So were as the ratio of heart failure (38.5% vs 13.8%, P = 0.000) and in-hospital mortality rate (4.4% vs 0.8%, P = 0.000). Logistic regression analysis demonstrated that the independent risk factors of heart failure included the value of E/Em and LVEF. CONCLUSION: Early E/Em is probably a powerful predictor for left ventricular remodeling and in-hospital heart failure in patients after acute myocardial infarction. PMID- 22321781 TI - [Expression of microRNA-223 and its clinical value in B lymphoproliferative disorders]. AB - OBJECTIVE: To detect the expression of microRNA-223 and analyze its clinical value in B lymphoproliferative disorders. METHODS: Peripheral blood samples (n = 78) and bone marrow samples (n = 9) were collected from patients with chronic lymphocytic leukemia (CLL, n = 53), mantle cell lymphoma (MCL, n = 13), splenic marginal zone lymphoma (SMZL, n = 9) and healthy donors (n = 12) at our hospital from 2003 to 2010. Mononuclear cells were isolated and B cells purified with a CD19(+) magnetic-bead system. Total RNA was extracted from purified CD19(+) cells and the expression of microRNA-223 measured by TaqMan microRNA quantitative polymerase chain reaction (PCR). The clinical data of these patients were collected and their outcomes analyzed with SPSS 16.0 software. RESULTS: (1) The levels of microRNA-223 in CLL, MCL and SMZL were 4.58 +/- 0.62, 4.03 +/- 0.54 and 4.63 +/- 0.57 respectively. And they were significantly lower than that in normal B cells (5.69 +/- 0.60, P < 0.01). The expression of microRNA-223 decreased significantly in MCL versus CLL and SMZL (P < 0.05). There was no statistical difference between CLL and SMZL (P > 0.05). (2) The down-regulation of microRNA 223 was associated with disease aggressiveness in CLL. Patients with unmutated immunoglobulin heavy chain variable region (IgVH) expressed significantly a lower level of microRNA-223 (4.05 +/- 0.69 vs 4.67 +/- 0.51, P = 0.003). In 13q negative patients, the expression of microRNA-223 decreased more significantly than that in 13q-positive patients (4.25 +/- 0.67 vs 4.76 +/- 0.45, P = 0.044). (3) Using receiver operating characteristic (ROC) curve analysis, the microRNA 223 cutoffs were defined according to the IgVH mutational status. The patients were divided into the positive and negative subgroups. The median progression free survival (PFS) of microRNA-223 positive patient subgroup was 48 months. It was significantly longer than the negative subgroup (P = 0.001). In the microRNA 223 positive subgroup, no patient died at the end of follow-up. CONCLUSIONS: MicroRNA-223 may play an important role in the pathogenesis of B lymphoproliferative disorders. The down-regulation of microRNA-223 is associated with disease aggressiveness and poor prognostic factors in CLL. It may become a new reliable prognostic predictor. PMID- 22321782 TI - [Impact of left ventricular systolic function on the outcomes of percutaneous coronary intervention for unprotected left main disease]. AB - OBJECTIVE: To evaluate the impact of left ventricular systolic function on the outcomes of percutaneous coronary intervention (PCI) for unprotected left main (ULM) disease. METHODS: The relevant baseline and outcome data of patients undergoing PCI for ULM disease at our hospital were collected from September 2006 to August 2009. The enrolled patients were divided into two groups according to left ventricular ejection fraction (LVEF): LVEF >= 40% group (n = 130) and LVEF < 40% group (n = 56). The baseline and outcome data were compared between two groups. Multivariable regression analysis was performed to appraise the prognostic role of LVEF < 40% in patients undergoing PCI for ULM disease. RESULTS: There were more patients with diabetes mellitus, a previous history of myocardial infarction, previous PCI/CABG (coronary artery bypass grafting) and NSTEMI (non-ST-segment elevation myocardial infarction) in LVEF < 40% group than LVEF >= 40% group (P < 0.05). The major adverse cardiovascular and cerebral vascular event (MACCE) rate was higher in LVEF < 40% group than LVEF >= 40% group (33.9% vs 18.5%, P = 0.022). And the rates of cardiac death, all-cause death and MI were also higher in LVEF < 40% group than LVEF >= 40% group (7.1% vs 1.5%, P = 0.047; 10.7% vs 3.1%, P = 0.034; 14.3% vs 4.6%, P = 0.022). Female gender, diabetes mellitus, previous PCI/CABG, NSTEMI/STEMI, LVEF < 40%, multiple-vessel disease, LM distal or bifurcation lesion and multiple-stent implantation were independent predictors of MACCE in patients undergoing PCI for ULM disease. CONCLUSION: Impaired left ventricular systolic function (LVEF < 40%)affects the prognosis of ULM patients undergoing PCI. Reduced LVEF (LVEF < 40%) is the strongest predictor of adverse events in these patients. PMID- 22321783 TI - [A scoring model for a differential diagnosis of tuberculous and non-tuberculous pleurisy]. AB - OBJECTIVE: To evaluate various clinical features and laboratory biochemical markers so as to develop a predictive model for differentiating tuberculous pleurisy (TBP) from non-tuberculous pleurisy (non-TBP). METHODS: A total of 241 TBP patients and 212 non-TBP patients who were hospitalized between January 2007 and December 2009 at our hospital were studied retrospectively. Their symptoms and laboratory parameters were recorded. The statistically different variables were selected to undergo binary logistic regression to calculate a scoring system (range: 0 - 10) according to their beta coefficients. A receiver operating characteristic (ROC) curve was used to calculate the best cut-off value. The performance of the model was tested in a sample of 82 new cases with pleural exudates. RESULTS: Seven variables were selected in the present scoring model: temperature > 38 degrees C (1.0 point), purified protein derivative testing positive (1.0 point), serum C-reactive protein >= 26 mg/L (1.5 points), pleural fluid lymphocyte percentage >= 85% (1.0 point), pleural fluid protein >= 49 g/L (1.0 point), pleural fluid adenosine deaminase >= 43 U/L (2.5 points) and serum and/or pleural fluid mycobacterium tuberculosis antibody positive (2.0 points). With a cut-off value of 6.0 points, the sensitivity, specificity and accuracy of differentiating TBP from non-TBP was 90.1%, 94.3% and 92.1% respectively. With the application of this model, 82 new pleural effusions showed a sensitivity of 94.1%, a specificity of 93.8% and an accuracy of 93.9%. CONCLUSION: The scoring model provided a simple and feasible way of facilitating a differential diagnosis of TBP and non-TBP patients. PMID- 22321784 TI - [Expression and significance of SARI and CCN1 in human colorectal carcinomas]. AB - OBJECTIVE: To explore the expressions of SARI (suppressor of AP-1, regulated by IFN) and connective tissue growth factor/cysteine-rich 61/nephroblastoma-1 (CCN1) and clarify their influences on the occurrence, development and prognosis of colorectal carcinoma (CRC). METHODS: Real-time PCR (polymerase chain reaction) was used to confirm the expressions of SARI and CCN1 at the mRNA level in 32 fresh tissue samples. And the expressions of Caco-2, HT-29 and Lovo were also detected by RT-PCR (reverse transcription-PCR) in cell lines. Tissue specimens were obtained from 116 cases of CRC and the expressions of SARI and CCN1 for each specimen detected by immunohistochemistry. The correlations between the expressions of SARI and CCN1 proteins were summarized. The relationships between the expression levels of SARI and CCN1 and their clinical features in primary CRC were analyzed respectively. The effects of expression levels of SARI and CCN1 proteins on the prognosis were also assessed in 116 CRC cases. RESULTS: The expressions of SARI and CCN1 at the mRNA level in fresh cancerous tissues and cell lines decreased and became up-regulated respectively. The positive rate of SARI protein expression was 76.7% and 28.4% in cancerous and noncancerous tissues respectively (P < 0.05). The positive rate of CCN1 protein expression was 26.7% and 74.1% in cancerous and noncancerous tissues respectively (P < 0.05). A negative correlation was observed between the expressions of SARI and CCN1 (r = 0.24, P < 0.05). The negative expression of SARI correlated with a low grade of differentiation, deep infiltration depth and high TNM staging (P < 0.05). A positive expression of CCN1 correlated with deep infiltration depth and high TNM staging (P < 0.05) while a negative expression of SARI correlated with a lower survival rate than that of a positive expression (chi(2) = 8.47, P < 0.05); additionally, the survival rate of patients with a negative expression of SARI plus a positive expression of CCN1 was further lowered (chi(2) = 12.56, P < 0.05). CONCLUSION: The aberrant expressions of SARI and CCN1 correlate with the malignant biobehaviors of CRC. And a negative expression of SARI correlates with a worse prognosis of CRC. PMID- 22321785 TI - [Clinical feature and analysis on the clinical related factors of BK virus associated nephropathy]. AB - OBJECTIVE: To determine the incidence of BK virus associated nephropathy (BKVAN) in renal-transplantation recipients, observe its histological features. METHODS: A total of 137 renal allograft biopsy specimens collected at our hospital during December 1999 to January 2008 were analyzed by routine histologic examination, immunohistochemistry and transmission electron microscopy (TEM) to screen for BKV. The case records of involved recipients were accessed to know their clinical manifestations, diagnostic characteristic and treatment regimens at that time. And the 1-, 3-year graft survival rate were analyzed by Kaplan-Meier analysis. RESULTS: A total of 16 renal biopsy specimens (11.7%) were positive for BKV. Viral particales on the size of 35 - 40 nm were seen in the tubular epithelial cells of 3 biopsy specimens and 7 urinary sediment samples. The numbers of BKVAN recipients suffering acute rejection, using ALG/ATG/OKT3 and using FK506+MMF immunosuppressive protocol were 7, 7 and 10 respectively. In 14 cases of BKVAN, there was an elevated level of serum creatine concentrations. Four cases lost their grafts after using a large dose of immunosuppressives. And renal functions improved by a reduction of immunosuppression or a replacement of FK506 with CsA in 8 cases. And graft functions deteriorated or had already failed in the remaining 4 cases whose immunosuppressive protocol were not changed. The 1-, 3 year graft survival rates were 81.3% and 54.2% in BKVAN recipients respectively. CONCLUSION: The diagnosis of BKVAN should be considered in recipients when their graft functions are deteriorating, especially for those with the accompanied risk factors. The morphological hallmarks of BKVAN are similar to those of acute rejection. The differentiation may be made by either immunohistochemistry or TEM. A proper modification of maintenance immunosuppression is effective in slowing down the progression of BKVAN. PMID- 22321786 TI - [Multicenter case-control study of the relationship between smoking and bladder cancer in China]. AB - OBJECTIVE: To explore the relationship between smoking and bladder cancer in China. METHODS: A multicenter case-control study was conducted from September 2005 to June 2008. A total of 432 bladder cancer patients, matched with 392 control cases, received a questionnaire including the type of exposure (active vs. passive smoking), the age of beginning and/or quitting smoking, smoking amount and time and depth of smoke inhalation. RESULTS: Both active smoking and passive smoking increased the incidence of bladder cancer (P < 0.05). Bladder cancer risk increased 1.89 times in active smokers and 1.88 times in passive smokers compared to non-smokers (P < 0.05). Smoke amount and time were significantly correlated with bladder cancer risk (P < 0.05). But the age of beginning smoking did not affect the bladder cancer risk (P > 0.05). Inhaling smoke into mouth or throat was also a risk factor for bladder cancer (P < 0.05). CONCLUSION: There is a strong association between smoking and bladder cancer. Active and passive smoking, smoke amount and time, and the depth of smoke inhalation are risk factors for bladder cancer. The best way of preventing bladder cancer is never smoking. PMID- 22321787 TI - [Novel exploration of emergency treatment for ueitic acute angle closure glacuma]. AB - OBJECTIVE: To explore the effects of anterior chamber paracentesis plus pupillary block relief under slit-lamp microscope for the emergency treatment of uveitic acute angle closure glaucoma (ACG). METHODS: In early stage, 14 uveitc acute ACG patients received anterior chamber paracentesis plus pupillary block relief while another 10 uveitc acute ACG patients underwent laser peripheral iridectomy (LPI). The intraocular pressure (IOP), degree of Tyndall, degree of pupillary block and severe adverse events were recorded at each observation timepoint. RESULTS: The IOP values for the paracentesis plus pupillary block relief group were (9.2 +/- 2.1) mm Hg, (12.4 +/- 3.7) mm Hg and (14.1 +/- 2.6) mm Hg at 1, 48 h and 10 d vs (24.5 +/- 7.1) mm Hg, (22.2 +/- 8.6) mm Hg and (19.3 +/- 9.3) mm Hg respectively for the LPI group. The inflammatory reaction of anterior chamber was more relieved in the paracentesis plus pupillary block relief group at Day 10. Pupillary block was observed in 1(1/14) patient from the paracentesis plus pupillary block relief group and 6 (6/10) patients from the LPI group at Day 10. Mild hemorrhage at pupillary margin was observed in 2 cases from the paracentesis plus pupillary block relief group. Both were self-absorbed within 10 days. CONCLUSION: Anterior chamber paracentesis plus pupillary block relief under slit lamp microscope is the safe and effective emergency treatment for uveitic acute ACG. And it may offer a basis for further therapy. PMID- 22321788 TI - [A compound heterozygous mutation in CYP17A1 gene in a female subject with partial 17alpha-hydroxylase/17, 20 lyase deficiency]. AB - OBJECTIVE: To explore the clinical and molecular genetic characteristics of a Chinese female patient with partial 17alpha-hydroxylase/17, 20 lyase deficiency (17OHD), a rare type of congenital adrenal hyperplasia. METHODS: Her clinical features and laboratory data were collected. Genomic DNA was extracted from leukocytes of peripheral blood of her and her mother. All eight exons of CYP17A1 gene, including flanking regions of introns, were amplified by PCR. The mutations of CYP17A1 gene were identified by direct sequencing or cloning and sequencing the amplified DNA fragments. RESULTS: The patient presented with hypertension, hypokalemia and irregular menstruation. DNA sequencing results demonstrated a compound heterozygous mutation in CYP17A1 gene. One allele of her had the deletion of phenylalanine (TTC) at either codon 53 or 54 and the other allele contained a base transversion at codon 329 (TAC/AA) and leading to a missense mutation of tyrosine to lysine and the open reading frame shift following this codon to produce a truncated enzyme with 417 amino acids and without activity site. Her mother was a heterozygous carrier of the latter allele. CONCLUSION: The partial 17OHD in this patient is caused by a compound heterozygous mutation in CYP17A1 gene. PMID- 22321789 TI - [Radiofrequency ablation for verapamil-sensitive ventricular tachycardia]. AB - OBJECTIVE: To assess the efficacy and safety of radiofrequency catheter ablation for verapamil-sensitive ventricular tachycardia (VT). METHODS: A total of 18 patients with a diagnosis of verapamil-sensitive VT were enrolled in this study. Radiofrequency catheter ablation was administered after underwent examinations on admission to rule out structural heart disease. the ablation catheter was placed around the left posterior intermediate septum and left anteroseptal in the left ventricular to searching for the Purkinje potential (P potential). When the Purkinje potential preceded the surface QRS by >= 20 ms, it was considered as an ideal target for ablation. Ablation at 25 - 35 W, 60 degrees C was often carried out at the point where the Purkinje potential was earliest. After ablation, perform programmed stimulation to measured the effects. The patients received routine postoperative treatment and care. And the follow-up period was 3 - 6 months after discharge. RESULTS: 17 patients diagnosed as ventricular raise from left posterior fascicle and 1 patient raise from left anterior fascicle were got to the radiofrequency end point and failed to elicit ventricular tachycardia again. In this patients, the Purkinje potential advanced to the starting point of QRS 20 ms were recognized as ideal point of radiofrequency. The length as the Purkinje potential advanced to the starting point of QRS are (24.0 +/- 3.5) ms. the more length, the less times of radiofrequency. No postoperative complications were noted except for 2 patients who had mild hematoma at the site of puncture. During the follow-up period, 2 patients were found to have relapsed (recurrence rate = 11.1%) and showed transient resistance to verapamil. The remaining patients had no previous history of tachycardia. CONCLUSION: With a low recurrence rate, radiofrequency ablation is a safe and efficacious cure for verapamil-sensitive VT. Despite some efficacies in the treatment of VT. PMID- 22321790 TI - [Relationship between jugular vein thrombosis and extremity vein thrombosis by vascular color Doppler ultrasound]. AB - OBJECTIVE: To explore the relationship between jugular vein thrombosis and extremity vein thrombosis in cancer patients by vascular color Doppler ultrasound. METHODS: A total of 79 cases with malignant tumors complicated with venous thrombosis undergoing vascular color Doppler ultrasound were analyzed retrospectively. All cases were divided into the group of jugular vein thrombosis (n = 36) and the group of extremity vein thrombosis (n = 43). The thrombotic factors of PT (prothrombin time), APTT (activated partial thromboplastin time), FIB (fibrinogen), HCT (hematocrit), PLT (platelet), PCT (plateletcrit), PDW (platelet distribution width), MPV (mean platelet volume), pathologic type and thrombotic time were compared between two groups. RESULTS: Between two groups, significant differences existed in APTT, pathologic types and before or after therapy (P < 0.05). However the other factors were not significant (P > 0.05). CONCLUSION: The clinicians should pay great attention to malignant tumor complicated with venous thromboembolism (VTE). An early diagnosis is essential to prevent pulmonary embolism (PE) and improve patient survival. Vascular color Doppler ultrasound may be used as the first-line examination. Preoperative and postoperative prophylactic anticoagulant therapy can reduce the risk of VTE in patients with high-risk factors. PMID- 22321791 TI - [Anatomical path of intraperitoneal radical nephrectomy: clinical experience of 60 cases]. AB - OBJECTIVE: To evaluate the safety and efficacy of intraperitoneal anatomical radical nephrectomy (IARN). METHODS: A retrospective analysis was performed for 60 consecutive patients undergoing IARN at our hospital from March 2007 to December 2009. Various clinical parameters were collected and analyzed statistically. RESULTS: Sixty operations were performed successfully. There was neither conversion into open surgery nor blood transfusion. The mean operative time was (106 +/- 23) min, mean intraoperative estimated blood loss (112 +/- 37) ml, mean time of resuming oral intake (2.1 +/- 0.7) d, mean time to ambulation (1.9 +/- 1.1) d, mean postoperative analgesics (pethidine) dosage (65 +/- 25) mg, average drainage volume 100 (50 - 300) ml, mean time of extracting drainage tube (3.6 +/- 1.3) d and mean postoperative hospital stay (9.4 +/- 2.1) d. CONCLUSION: IARN offers the advantages of distinct anatomical level, shorter operative time, less hemorrhage, less damage, faster postoperative recovery and a lower rate of complications. PMID- 22321792 TI - [Correlation between age-related hearing loss and impairment of cognition in C57BL/6J mice]. AB - OBJECTIVE: To explore the correlation of age-related hearing loss and cognition impairment in C57BL/6J mice by observing hearing, cognitive function and synapses. METHODS: C57BL/6J and CBA/CaJ mice were divided into 3 groups. The hearing and cognitive functions of each animal was tested. And the ultrastructure of synapses was simultaneously observed for C57BL/6J mice. RESULTS: The 24-26 week-old C57BL/6J mice developed moderate hearing loss while the 42-44-week-old C57BL/6J counterparts suffered profound hearing loss. Whereas excellent hearing was maintained in 3 groups of CBA/CaJ mice within 44 weeks. During cognitive test, the performance of 42-44-week-old C57BL/6J mice was significantly worse than CBA/CaJ mice. During probe test, the number of platform crossing of 42-44 week-old C57BL/6J mice was smaller than that of CBA/CaJ mice (0.5 +/- 0.6 vs 1.9 +/- 1.6; P < 0.05). The 42-44-week-old C57BL/6J mice had a wider synaptic cleft and a thinner postsynaptic density than the 24-26-week-old C57BL/6J counterparts [synaptic cleft: (19.4 +/- 0.5) nm vs (11.9 +/- 0.7) nm; postsynaptic density: (15.2 +/- 0.5) nm vs (27.8 +/- 2.0) nm; both P < 0.05]. Furthermore, the degeneration of synapses in hippocampus CA3 area of C57BL/6J mice were clearly observed at 42 - 44 weeks of age, but not seen in CBA/CaJ mice. CONCLUSION: Age related hearing loss might impact on the cognition impairment in C57BL/6J mice. PMID- 22321793 TI - [Apigenin regulates lipopolysaccharides-induced activation of inflammasome]. AB - OBJECTIVE: To evaluate whether or not apigenin regulates the activation of inflammasome and elucidate its underlying mechanism. METHODS: Cultured THP-1 (acute monocytic leukemia cell line) cells were treated with dimethyl sulfoxide (DMSO) alone (control group), lipopolysaccharides (LPS), LPS plus apigenin (25/50 umol/L) or LPS plus Z-VAD (a caspase inhibitor). The supernatant was harvested and the content of secreted interleukin (IL)-1beta was determined by enzyme linked immunosorbent assay (ELISA). The effects of apigenin on the cleavage of pro-IL-1beta and pro-caspase-1 were determined by Western blot. And the effect of apigenin on the nuclear factor (NF)-kappaB activation was detected by reporter gene assay. RESULTS: MTT assays showed that the cytotoxicity of apigenin was low. Apigenin could significantly inhibit the LPS-induced secretion of IL-1beta in THP 1 cells. The concentration of IL-1beta was (362 +/- 64) pg/ml in the control group, (1549 +/- 320) pg/ml in the LPS group, (397 +/- 150) pg/ml in the LPS plus 25 umol/L apigenin group and (268 +/- 142) pg/ml in the LPS plus 50 umol/L apigenin group (P < 0.05). The results of Western blot indicated that apigenin inhibited the maturation of pro-IL-1beta and pro-caspase-1. It could also inhibit the LPS-induced activation of NF-kappaB. The value of relative light unit was 0.6 +/- 0.1 in the control group, 32.7 +/- 0.8 in the LPS group, 12.9 +/- 1.8 in the LPS plus 25 umol/L apigenin group and 10.0 +/- 3.2 in the LPS plus 50 umol/L apigenin group respectively (P < 0.05). CONCLUSION: Apigenin may inhibit the LPS induced activation of inflammasome through an inhibited muturation of caspase-1. PMID- 22321794 TI - The structures of coiled-coil domains from type III secretion system translocators reveal homology to pore-forming toxins. AB - Many pathogenic Gram-negative bacteria utilize type III secretion systems (T3SSs) to alter the normal functions of target cells. Shigella flexneri uses its T3SS to invade human intestinal cells to cause bacillary dysentery (shigellosis) that is responsible for over one million deaths per year. The Shigella type III secretion apparatus is composed of a basal body spanning both bacterial membranes and an exposed oligomeric needle. Host altering effectors are secreted through this energized unidirectional conduit to promote bacterial invasion. The active needle tip complex of S. flexneri is composed of a tip protein, IpaD, and two pore forming translocators, IpaB and IpaC. While the atomic structure of IpaD has been elucidated and studied, structural data on the hydrophobic translocators from the T3SS family remain elusive. We present here the crystal structures of a protease stable fragment identified within the N-terminal regions of IpaB from S. flexneri and SipB from Salmonella enterica serovar Typhimurium determined at 2.1 A and 2.8 A limiting resolution, respectively. These newly identified domains are composed of extended-length (114 A in IpaB and 71 A in SipB) coiled-coil motifs that display a high degree of structural homology to one another despite the fact that they share only 21% sequence identity. Further structural comparisons also reveal substantial similarity to the coiled-coil regions of pore-forming proteins from other Gram-negative pathogens, notably, colicin Ia. This suggests that these mechanistically separate and functionally distinct membrane-targeting proteins may have diverged from a common ancestor during the course of pathogen-specific evolutionary events. PMID- 22321795 TI - Large is fast, small is tight: determinants of speed and affinity in subunit capture by a periplasmic chaperone. AB - The chaperone/usher pathway assembles surface virulence organelles of Gram negative bacteria, consisting of fibers of linearly polymerized protein subunits. Fiber subunits are connected through 'donor strand complementation': each subunit completes the immunoglobulin (Ig)-like fold of the neighboring subunit by donating the seventh beta-strand in trans. Whereas the folding of Ig domains is a fast first-order process, folding of Ig modules into the fiber conformation is a slow second-order process. Periplasmic chaperones separate this process in two parts by forming transient complexes with subunits. Interactions between chaperones and subunits are also based on the principle of donor strand complementation. In this study, we have performed mutagenesis of the binding motifs of the Caf1M chaperone and Caf1 capsular subunit from Yersinia pestis and analyzed the effect of the mutations on the structure, stability, and kinetics of Caf1M-Caf1 and Caf1-Caf1 interactions. The results suggest that a large hydrophobic effect combined with extensive main-chain hydrogen bonding enables Caf1M to rapidly bind an early folding intermediate of Caf1 and direct its partial folding. The switch from the Caf1M-Caf1 contact to the less hydrophobic, but considerably tighter and less dynamic Caf1-Caf1 contact occurs via the zip out-zip-in donor strand exchange pathway with pocket 5 acting as the initiation site. Based on these findings, Caf1M was engineered to bind Caf1 faster, tighter, or both faster and tighter. To our knowledge, this is the first successful attempt to rationally design an assembly chaperone with improved chaperone function. PMID- 22321796 TI - A molecular history of the amyloidoses. AB - The molecular investigation of the amyloidoses began in the mid-19th century with the observation of areas in human tissues obtained at autopsy that were homogeneous and eosinophilic with conventional stains but became blue when exposed to mixtures of iodine and sulfuric acid. The foci corresponded to regions formerly identified as "waxy" or lardaceous. Subsequent identification of the characteristic staining of the same tissues with metachromatic dyes such as crystal violet or with the cotton dye Congo red (particularly under polarized light) and thioflavins allowed the pathological classification of those tissues as belonging to a set of disorders known as the amyloidoses. Not unexpectedly, progress has reflected evolving technology and parallel advances in all fields of biological science. Investigation using contemporary methods has expanded our notions of amyloid proteins from being simply agents or manifestations of systemic, largely extracellular diseases to include "protein-only infection," the concept that "normal" functional amyloids might exist in eukaryotes and prokaryotes and that aggregatability may be an intrinsic structural price to be paid for some functional protein domains. We now distinguish between the amyloidoses, that is, diseases caused by the deposition of amyloid fibrils and amyloid proteins (i.e., purified or recombinant proteins that form amyloid fibrils in vitro), which may or may not be associated with disease in vivo. PMID- 22321797 TI - The effect of Abeta on IAPP aggregation in the presence of an isolated beta-cell membrane. AB - Fibrillar aggregates of the islet amyloid polypeptide (IAPP) and amyloid-beta (Abeta) are known to deposit at pancreatic beta-cells and neuronal cells and are associated with the cell degenerative diseases type-2 diabetes mellitus (T2DM) and Alzheimer's disease (AD), respectively. Since IAPP is secreted by beta-cells and a membrane-damaging effect of IAPP has been discussed as a reason for beta cell dysfunction and the development of T2DM, studies of the interaction of IAPP with the beta-cell membrane are of high relevance for gaining a molecular-level understanding of the underlying mechanism. Recently, it has also been shown that patients suffering from T2DM exhibit an increased risk to develop AD and vice versa, and a molecular link between AD and T2DM has been suggested. In this study, membrane lipids from the rat insulinoma-derived INS-1E beta-cell line were isolated, and their interaction with the amyloidogenic peptides IAPP and Abeta and a mixture of both peptides has been studied. To yield insight into the associated peptides' conformational changes and their effect on the membrane integrity during aggregation, we have carried out attenuated total reflection Fourier transform infrared spectroscopy, fluorescence microscopy, and atomic force microscopy experiments. The IAPP-Abeta heterocomplexes formed were shown to adsorb, aggregate, and permeabilize the isolated beta-cell membrane significantly slower than pure IAPP, however, at a rate that is much faster than that of pure Abeta. In addition, it could be shown that isolated beta-cell membranes cause similar effects on the kinetics of IAPP and IAPP-Abeta fibril formation as anionic heterogeneous model membranes. PMID- 22321798 TI - A template RNA entry channel in the fingers domain of the poliovirus polymerase. AB - Positive-strand RNA viruses within the Picornaviridae family express an RNA dependent RNA polymerase, 3D(pol), that is required for viral RNA replication. Structures of 3D(pol) from poliovirus, coxsackievirus, human rhinoviruses, and other picornaviruses reveal a putative template RNA entry channel on the surface of the enzyme fingers domain. Basic amino acids and tyrosine residues along this entry channel are predicted to form ionic and base stacking interactions with the viral RNA template as it enters the polymerase active site. We generated a series of alanine substitution mutations at these residues in the poliovirus polymerase and assayed their effects on template RNA binding, RNA synthesis initiation, rates of RNA elongation, elongation complex (EC) stability, and virus growth. The results show that basic residues K125, R128, and R188 are important for template RNA binding, while tyrosines Y118 and Y148 are required for efficient initiation of RNA synthesis and for EC stability. Alanine substitutions of tyrosines 118 and 148 at the tip of the 3D(pol) pinky finger drastically decreased the rate of initiation as well as EC stability, but without affecting template RNA binding or RNA elongation rates. Viable poliovirus was recovered from HeLa cells transfected with mutant RNAs; however, mutations that dramatically inhibited template RNA binding (K125A-K126A and R188A), RNA synthesis initiation (Y118A, Y148A), or EC stability (Y118A, Y148A) were not stably maintained in progeny virus. These data identify key residues within the template RNA entry channel and begin to define their distinct mechanistic roles within RNA ECs. PMID- 22321799 TI - YajL, the prokaryotic homolog of the Parkinsonism-associated protein DJ-1, protects cells against protein sulfenylation. AB - YajL is the closest Escherichia coli homolog of the Parkinsonism-associated protein DJ-1, a multifunctional oxidative stress response protein whose biochemical function remains unclear. We recently described the oxidative-stress dependent aggregation of proteins in yajL mutants and the oxidative-stress dependent formation of mixed disulfides between YajL and members of the thiol proteome. We report here that yajL mutants display increased protein sulfenic acids levels and that formation of mixed disulfides between YajL and its protein substrates in vivo is inhibited by the sulfenic acid reactant dimedone, suggesting that YajL preferentially forms disulfides with sulfenylated proteins. YajL (but not YajL(C106A)) also forms mixed disulfides in vitro with the sulfenylated form of bovine serum albumin. The YajL-serum albumin disulfides can be subsequently reduced by glutathione or dihydrolipoic acid. We also show that DJ-1 can form mixed disulfides with sulfenylated E. coli proteins and with sulfenylated serum albumin. These results suggest that YajL and possibly DJ-1 function as covalent chaperones involved in the detection of sulfenylated proteins by forming mixed disulfides with them and that these disulfides are subsequently reduced by low-molecular-weight thiols. PMID- 22321800 TI - Regional practice patterns for retinal detachment repair in the United States. AB - PURPOSE: To determine if there are variations in regional practice patterns for retinal detachment repair in the United States. DESIGN: Retrospective, noninterventional, cross-sectional study. METHODS: Year 2009 Medicare fee-for service claims for retinal detachment repair were aggregated in 4 geographic regions and evaluated. The relative preference for retinal detachment repair by pars plana vitrectomy, scleral buckling, and pneumatic retinopexy was analyzed. RESULTS: The Midwest demonstrated a greater preference for scleral buckling compared to all other regions (P < .01) and lower preference for pars plana vitrectomy relative to the South and West (P <= .02). The Northeast demonstrated a greater preference for pneumatic retinopexy when compared to all other regions (P < .01). The Northeast also revealed a trend toward a lower preference for pars plana vitrectomy compared to the West and South (P <= .08). CONCLUSION: There are statistically significant variations in regional practice patterns for retinal detachment repair. The West, despite its historical association with pneumatic retinopexy, did not demonstrate a greater preference for the surgical technique. PMID- 22321801 TI - Prevalence of inflammatory back pain in a cohort of patients with anterior uveitis. AB - PURPOSE: To determine the prevalence of inflammatory back pain in an anterior uveitis cohort. DESIGN: Retrospective cohort study. METHODS: Patients with anterior uveitis were recruited from the clinic of an ophthalmologist to complete a survey between March and December 2008. Patients were classified with inflammatory back pain if they had >=2 positive responses to 4 validated inflammatory back pain questions: presence of morning stiffness >30 minutes in duration; improvement in back pain with exercise but not with rest; awakening from back pain during the second half of the night only; and presence of alternating buttock pain. Disease activity was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The impact of disease on quality of life was measured using the EuroQOL (EQ-5D) questionnaire. Twenty-five patients underwent further rheumatologic examination. RESULTS: One hundred forty-one of 167 patients (84.4%) completed the survey. Sixty-six of 141 patients (46.8%) were classified to have inflammatory back pain. Mean BASDAI (4.2, SD 2.41) and EQ-5D scores (0.73, SD 0.21) were lower than patients with no inflammatory back pain (0.82, SD 0.16, P = .0048). In the subgroup that underwent rheumatologic assessment, a classification of inflammatory back pain was 92% sensitive and 67% specific for a diagnosis of inflammatory back pain. CONCLUSIONS: The prevalence of inflammatory back pain in a cohort of anterior uveitis patients was found to be 46.8%. Patients with inflammatory back pain had worse quality of life than those without. Ophthalmologists may use these questions on back pain to select patients classified to have inflammatory back pain to refer for early rheumatologic assessment. PMID- 22321802 TI - Treatment patterns for neovascular age-related macular degeneration: analysis of 284 380 medicare beneficiaries. AB - PURPOSE: To examine trends in the treatment of newly diagnosed neovascular age related macular degeneration (AMD). DESIGN: Retrospective cohort study. METHODS: Among 284 380 Medicare beneficiaries with a new diagnosis between 2006 and 2008, we used the cumulative incidence function to estimate procedure rates and the mean frequency function to estimate the cumulative mean number of intravitreous injections. We used Cox log-binomial regression to estimate predictors of the use of vascular endothelial growth factor (VEGF) antagonists within 1 year after diagnosis. Discontinuation of anti-VEGF therapy was defined by absence of treatment for 12 months. Discontinuation rates were calculated using the Kaplan Meier method. RESULTS: The proportion of patients receiving anti-VEGF therapy increased from 60.3% to 72.7%, photodynamic therapy decreased from 12.8% to 5.3%, and thermal laser treatment decreased from 5.5% to 3.2%. Black patients (hazard ratio, 0.77; 95% confidence interval, 0.75-0.79) and patients of other/unknown race (0.83; 0.81-0.84) were less likely than white patients to receive anti-VEGF therapy. Patients with dementia were less likely to receive anti-VEGF therapy (0.88; 0.88-0.89). Among patients who received anti-VEGF therapy, the mean number of injections within 1 year of the first injection was 4.3 per treated eye. Anti VEGF therapy was discontinued in 53.6% of eyes within 1 year, and in 61.7% of eyes within 18 months. CONCLUSIONS: Treatment of new neovascular AMD changed significantly between 2006 and 2008, most notably in the increasing use of anti VEGF therapies. However, few patients treated with anti-VEGF medications received monthly injections, and discontinuation rates were high. PMID- 22321803 TI - Prevalence and severity of fuchs corneal dystrophy in Tangier Island. AB - PURPOSE: To investigate the clinical and genetic features of late-onset Fuchs corneal dystrophy (FCD) on Tangier, an island in the Chesapeake Bay with an isolated population of approximately 500 individuals. DESIGN: Observational, cross-sectional study. METHODS: A total of 156 individuals born to inhabitants of Tangier Island volunteered to undergo ophthalmic evaluation. Medical history was ascertained prior to examination. All participants underwent anterior segment examination with slit-lamp biomicroscopy. Retroillumination photographs were acquired from affected individuals and the disease severity was compared with individuals from large families ascertained previously. Genomic DNA samples were investigated for the presence of the recently identified risk allele rs613872, an intronic variant of TCF4. RESULTS: Of the 148 examined individuals who were at least 30 years of age, 32 showed the classical symptoms of late-onset FCD (21.6%), providing a minimum prevalence of 11% among individuals over the age of 50 years. Severity was significantly lower compared to 51 cases from unlinked families, among individuals either 50 to 70 or above 70 years of age (P = .05 and P = .01, respectively). Retroillumination photography analyses were suggestive of mild severity when compared with the disease phenotype associated with FCD1- and FCD2-linked families. The rs613872 variant was associated with a higher affectation rate (P = .01), while the wild-type allele was correlated with a higher proportion of subclinical disease (P = .01). CONCLUSIONS: In this study population in Tangier, late-onset FCD manifests clinically with a mild phenotype and increased prevalence. The rs613872 variant correlates with increased affectation and a clinical disease phenotype. PMID- 22321804 TI - Clinical and ultrasound biomicroscopy features associated with growth in iris melanocytic lesions. AB - PURPOSE: To determine the clinical and ultrasound biomicroscopy (UBM) features associated with growth in iris melanocytic lesions. STUDY DESIGN: Retrospective case series analysis. METHODS: We included all iris melanocytic lesions that were monitored between January 2005 and November 2009. At the end of the analysis, 44 eyes of 44 patients were included in the final analysis. The clinical features analyzed were: iris color, largest base diameter, radial location of the lesion epicenter, circumferential location of the lesion epicenter, lesion configuration, lesion pigmentation, intrinsic vascularity within the lesion, presence of associated pigmentation, the impact on the pupil, presence of iris atrophy, and lesion-induced localized cataracts. The UBM features included lesion thickness, presence of corneal touch, presence of surface plaque, internal structure, and internal reflectivity. Regression analysis was performed to define the features associated with growth. RESULTS: Twenty-three percent of the lesions showed documented growth. Mean follow-up was 21.4 months (range: 10-48). Clinical features associated with growth were a large basal diameter at baseline (P = .004) and inferior location (P = .004). UBM features associated with growth were: a greater baseline thickness (P = .01), presence of corneal touch (P = .007), an irregular internal structure (P = .0001), and the presence of dots and linear streaks (P < .0001). Clinical features that were not associated with growth were the radial location of the lesion in the iris (P > .999), lesion configuration (P > .999), lesion pigmentation (P > .999), the presence of pigment dispersion (P = .70), iris freckles (P = .15), corectopia (P > .999), ectropion (P > .999), and intrinsic vascularity (P = .70). UBM features not associated with growth were the presence of a surface plaque (P = .07) and the internal reflectivity (P = .77). CONCLUSION: Substantial growth in iris melanocytic lesions is associated with original larger basal diameter and inferior lesion location. On UBM growth is associated with greater original thickness, presence of corneal touch, and an irregular internal structure. Presence of these features could modify the frequency of observation of those lesions. PMID- 22321805 TI - Microperimetric correlations of autofluorescence and optical coherence tomography imaging in dry age-related macular degeneration. AB - PURPOSE: To investigate the microperimetric correlations of autofluorescence imaging and optical coherence tomography (OCT) in dry age-related macular degeneration (AMD). DESIGN: Retrospective, observational, cross-sectional study. METHODS: Consecutive patients with dry AMD underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA), blue fundus autofluorescence (FAF), near-infrared autofluorescence, and spectral-domain (SD) OCT with integrated microperimetry. RESULTS: A total of 58 eyes of 29 patients (21 women; mean age 73 +/- 9 years) were included. Mean BCVA was 0.28 +/- 0.3 logarithm of the minimal angle of resolution (logMAR). Overall, 2842 points were analyzed as regards FAF and near-infrared autofluorescence patterns, the status of inner segment/outer segment (IS/OS) interface, and retinal sensitivity. We observed a good correlation between the FAF and near-infrared autofluorescence patterns for all the points graded (increased FAF/near-infrared autofluorescence, Pearson rho = 0.6, P = .02; decreased FAF/near-infrared autofluorescence, Pearson rho = 0.7, P = .01; normal FAF/near-infrared autofluorescence, Pearson rho = 0.7, P = .01). Mean retinal sensitivity was significantly reduced in cases of decreased FAF (4.73 +/- 2.23 dB) or increased FAF (4.75 +/- 2.39 dB) compared with normal FAF (7.44 +/- 2.34 dB) (P = .001). Mean retinal sensitivity was significantly reduced in case of decreased near-infrared autofluorescence (3.87 +/- 2.28 dB), compared with increased near-infrared autofluorescence (5.76 +/- 2.44 dB) (P = .02); mean retinal sensitivity in case of increased near-infrared autofluorescence was significantly reduced compared with normal near-infrared autofluorescence (7.15 +/- 2.38 dB) (P = .002). On SD-OCT, there was a high inverse correlation between retinal sensitivity and rate of disruptions in IS/OS interface (Pearson rho = -0.72, P = .001). CONCLUSION: A reduced retinal sensitivity consistently correlates with decreased FAF/near-infrared autofluorescence and a disrupted IS/OS interface. Increased near-infrared autofluorescence may represent a useful method for detection of retinal abnormalities early in dry AMD development. PMID- 22321806 TI - Pet ownership and older women: the relationships among loneliness, pet attachment support, human social support, and depressed mood. AB - Pets can play a positive role in the both the physical and psychological health of older adults. This cross sectional study investigated the relationships among loneliness, pet attachment support, human social support, and depressed mood in a convenience sample of 159 pet-owning older women residing in the community. Participants completed loneliness, pet attachment support, human social support, and depressed mood scales. The results supported significant relationships between loneliness, pet attachment support, human social support, and depressed mood. No relationship was found between human social support and depressed mood. Pet attachment support, but not human social support, influenced the relationship between loneliness and depressed mood indicating the importance of pet attachment as a greater form of support in this sample. Clinical and social implications for nurses working with the geriatric population were identified and discussed. PMID- 22321807 TI - Reactions of assisted living staff to behavioral and psychological symptoms of dementia. AB - This study investigates the experiences of unlicensed staff providing care for older adults with behavioral and psychological symptoms of dementia (BPSD). The purpose of this study was to describe the types and frequency of BPSD reported by unlicensed caregivers and to describe reactions and training of the caregivers who provide care to residents with BPSD. Data were derived from 87 staff-resident dyads in twelve assisted living facilities (ALFs). Types and frequency of BPSD and staff reaction to BPSD were collected using standardized measures. Demographic data included amount of staff training related to caring for someone with BPSD. Dementia related behaviors and psychological symptoms were prevalent in the ALF residents, with memory related symptoms being the most frequently reported. Symptoms of depression in the ALF residents were less frequent yet accounted for the highest level of staff reaction. Limited training related to caring for residents with cognitive impairment was reported by staff. Developing ALF staff skills in identifying and managing depression in older adults with dementia may serve a dual purpose of improving quality of life for residents and for ALF staff. PMID- 22321808 TI - CD4+ and gammadeltaTCR+ T lymphocytes are sources of interleukin-17 in swine. AB - In the veterinary field, only limited information is available about interleukin 17A (IL-17), despite the fact that this cytokine plays an important role during pro-inflammatory immune responses and induces the production of chemotactic factors for neutrophils. The aim of this study was to characterize porcine IL-17 producing cells. We tested the cross-reactivity of five anti-human IL-17 monoclonal antibodies because such antibodies against porcine IL-17 are currently unavailable. Whole blood cells (WBCs) were stimulated with phorbol-myristate acetate (PMA) and ionomycin and subsequently analyzed by flow cytometry. The antibody clone SCPL1362 was found to cross-react with porcine IL-17, whereas the other four antibodies tested did not recognize this cytokine. Using this antibody, we characterized porcine WBC-secreting IL-17 after PMA and ionomycin stimulation. All IL-17-producing WBCs were positive for the T lymphocyte marker CD3. Myeloid cells (CD172alpha(+)) and B lymphocytes (CD79alpha(+)) were IL-17 negative. The major subset of IL-17 positive T lymphocytes was the CD4(+) lymphocytes (about 60% of all IL-17 positive WBCs). The remaining IL-17 positive WBCs were gammadeltaTCR(+) lymphocytes. CD8 positive and CD8 negative cells were found within both CD4(+) and gammadeltaTCR(+) cells producing the cytokine. Moreover, IL-17 positive cells were mostly CD45RA negative, therefore activated cells or memory cells. Flow cytometry data were confirmed using sorted cells. Both sorted CD4(+) and gammadeltaTCR(+) cells produced IL-17 at mRNA level after PMA and ionomycin stimulation while double negative CD4(-)gammadeltaTCR(-) cells were negative for IL-17. We can conclude that only two subpopulations of porcine WBCs are sources of IL-17 after non-specific stimulation: CD3(+)CD4(+) and CD3(+)gammadeltaTCR(+). PMID- 22321809 TI - Potent synergistic effect of IL-3 and TNF on matrix metalloproteinase 9 generation by human eosinophils. AB - TNF (designated as TNF-alpha under previous nomenclature) is the preeminent activator of MMP-9 generation from a variety of cells including eosinophils. We have previously established that TNF strongly synergizes with IFN-gamma and IL-4 for eosinophil synthesis of Th1- and Th2-type chemokines respectively. Thus, we sought to determine if TNF-induced synthesis of MMP-9 would be enhanced by the presence of Th1, Th2, or the eosinophil-associated common beta chain (betac) cytokines. Human blood eosinophils were cultured with TNF alone or in combination with either IFN-gamma, IL-4, IL-3, IL-5, or GM-CSF. Concentrations and activities of MMP-9 in eosinophil culture supernates were measured by ELISA and gelatin zymography, mRNA transcription and stabilization by quantitative real-time PCR, and signaling events by immunoblotting and intracellular flow cytometric analysis. Individually, TNF, GM-CSF, or IL-3, but not IL-4 or IFN-gamma, induced relatively small (<0.2 ng/ml) but statistically significant quantities of MMP-9. Remarkable synergistic synthesis of MMP-9 (ng/ml levels) occurred in response to TNF plus IL-3, GM-CSF or IL-5, in the order of IL-3>GM-CSF>IL-5. Zymography revealed that eosinophils release MMP-9 in its pro-form. Eosinophil stimulation with the combination of IL-3 plus TNF led to increased steady-state levels of MMP 9 mRNA, prolonged mRNA stabilization, and enhanced activation of ERK1/2 phosphorylation. Inhibition of NF-kappaB, MEK kinase, or p38 MAP kinase, but not JNK signaling pathways, diminished IL-3/TNF-induced MMP-9 mRNA and protein production. Thus, the synergistic regulation of eosinophil MMP-9 by IL-3 plus TNF likely involves cooperative interaction of multiple transcription factors downstream from ERK, p38, and NF-kappaB activation as well as post transcriptional regulation of MMP-9 mRNA stabilization. Our data indicate that within microenvironments rich in betac-family cytokines and TNF, eosinophils are an important source of proMMP-9 and highlight a previously unrecognized role for synergistic interaction between TNF and betac-family cytokines, particularly IL 3, for proMMP-9 synthesis. PMID- 22321810 TI - The use of a lacertid lizard as a model for reptile ecotoxicology studies--part 1 field demographics and morphology. AB - At the European level, lacertid lizards have been proposed as potential model species for reptile ecotoxicology. We studied demographic and morphological aspects of natural field subpopulations of Podarcis bocagei inhabiting similar agricultural habitats which were either regularly exposed to pesticides, or not. Parameters examined in this study included population size and density, sex ratio, adult body size, fluctuating asymmetry in femoral pores and parasite prevalence. In general, we detected few statistically significant differences between the exposed and reference subpopulations. Although field situations are ecologically complex and factors other than pesticides may be acting, the absence of observable effects on field subpopulations is probably indicative that lizards are coping or compensating for this level of exposure. PMID- 22321811 TI - A technique for concurrent procedure of mastoid obliteration and meatoplasty after canal wall down mastoidectomy. AB - OBJECTIVE: To present a simple technique for concurrent procedure of mastoid obliteration and meatoplasty after canal wall down mastoidectomy, and to assess the efficacy and the surgical results of this technique. METHODS: Retrospective clinical study of a consecutive series of procedures from 2004 to 2008. One hundred thirteen patients undergone canal wall down mastoidectomy with tympanoplasty and concurrent procedure of mastoid obliteration and meatoplasty that uses an anteriorly based musculoperiosteal flap and a horizontal skin incision on the concha were included. Preoperative diagnoses were classified into cholesteatoma, adhesive otitis media, and chronic suppurative otitis media. The mean duration of follow-up was 38 months, with a range of 12-75 months. We analyzed control of suppuration and creation of a dry mastoid cavity according to the Merchant's grading system for evaluation of the efficacy of this technique, and hearing outcome. We evaluated postoperative complications including development of recurrent or residual cholesteatomas and duration of the mastoid cavity achieving a complete healing. RESULTS: Seventy-two patients had cholesteatoma, whereas 27 patients had adhesive otitis media and 14 patients had chronic suppurative otitis media. Eighty-three percent of all patients, in 86% of patients with cholesteatoma, in 78% of patients with adhesive otitis media, and in 78% of patients with chronic suppurative otitis media were achieved a dry and self-cleaning mastoid and complete control of infection. Duration of the mastoid cavity achieving a dry and self-cleaning mastoid ranged from 4 weeks to 24 weeks and the mean time of the complete epithelialization was 11.1+/-4.6 weeks. The average ABGs were 32.4+/-13.8dB preoperatively and 23+/-13.2dB postoperatively. There were 5 patients with failure of control of infection postoperatively and 3 patients of recidivistic cholesteatoma. CONCLUSION: The efficacy of our technique to make a dry and healthy mastoid cavity after a canal wall down mastoidectomy is satisfactory, and the rate of complication is acceptably low. We believe that our technique could be a convenient method to prevent cavity problems after canal wall down mastoidectomy. PMID- 22321812 TI - External work is deficient in both limbs of patients with unilateral PAD. AB - External work was utilized to measure differences between the unaffected and the affected limb in patients with unilateral peripheral arterial disease compared to healthy controls. Patients with unilateral peripheral arterial disease have shown deficits in peak joint powers during walking in the unaffected and affected legs. However, no research has detailed the amount of work that is being performed by each leg compared to healthy controls even though such an analysis would provide valuable information on the energy output from the affected and the unaffected legs. Two hypotheses were tested: (a) the unaffected and affected leg would perform less work than healthy controls in a pain-free state, and (b) the onset of symptomatic claudication pain would result in further changes in the external work. Results showed that during a pain-free state, both the unaffected and affected legs perform less work than the healthy controls. After onset of claudication pain, the work output by the affected limb becomes further decreased while the unaffected limb experiences changes in negative external work. These findings combined with recent evidence of decreased peak powers in both legs in unilateral peripheral arterial disease patients reflects altered pathomechanics in both limbs compared to healthy controls. PMID- 22321813 TI - Laparoscopic transperitoneal pyeloplasty in children from age of 3 years: our clinical outcomes compared with open surgery. AB - OBJECTIVE: To report clinical outcomes for laparoscopic pyeloplasty (LP) in children compared with open pyeloplasty (OP) and literature findings. PATIENTS AND METHODS: In a prospective study, the outcomes of 57 consecutive transperitoneal LP in children from the age of 3 years were analyzed and compared with a matched historic control group of OP and with series of LP in the literature. Successful result was defined as resolution of symptoms, no conversion or re-operation, improved hydronephrosis, and/or improved renographic drainage. RESULTS: Mean operative time was 177 (SD 50.5)min in the LP group and 108 (SD 25.6)min in the OP group (p < 0.001). Mean hospital stay was 1.2 (SD 0.46) days in the LP and 6.7 (SD 1.2) days in the OP group. Improvement in renographic drainage was observed more often after LP than after OP (98% vs 83%; p = 0.010). A successful result was reported in 56 (98%) LP and 54 (95%) OP (p = 0.298) patients. Our LP series demonstrates a high success rate compared to literature data. CONCLUSIONS: Our LP has a similar success rate and more often improved renographic drainage in comparison to OP. Furthermore, our LP demonstrates a shorter hospital stay and favorable outcomes compared to the literature. We thus regard LP as standard treatment for repair of ureteropelvic junction obstruction in children from the age of 3 years. PMID- 22321814 TI - Perceived barriers to care and attitudes towards shared decision-making among low socioeconomic status parents: role of health literacy. AB - OBJECTIVE: Although low parent health literacy (HL) has been linked to poor child health outcomes, it is not known whether differences in perceptions related to access to care and provider-parent partnership in care are potential contributing factors. We sought to assess whether parent HL is associated with differences in perceived barriers to care and attitudes regarding participatory decision-making with the provider. METHODS: This was a cross-sectional analysis of data collected from parents presenting with their child to an urban public hospital pediatric clinic in New York City. Dependent variables were caregiver-reported barriers to care (ability to reach provider at night/on weekends, difficult travel to clinic) and attitudes towards participatory decision-making (feeling like a partner, relying on doctor's knowledge, leaving decisions up to the doctor, being given choices/asked opinion). The primary independent variable was caregiver HL (Short Test of Functional Health Literacy in Adults [S-TOHFLA]). RESULTS: A total of 823 parents were assessed; 1 in 4 (27.0%) categorized as having low HL. Parents with low HL were more likely to report barriers to care than those with adequate HL: trouble reaching provider nights/weekends, 64.9% vs. 49.6%, (p < 0.001, adjusted odds ratio [AOR] 1.7, 95% confidence interval [95% CI] 1.2-2.4); difficult travel, 15.3% vs. 8.0%, (p = 0.004, AOR 1.8, 95% CI 1.1-3.0). Low HL was also associated with not feeling like a partner (28.8% vs. 17.1%; AOR 2.0; 95% CI 1.4 3.0), preference for relying on the doctor's knowledge (68.9% vs. 52.2%; AOR 1.7; 95% CI 1.2-2.4), and preference for leaving decisions up to the doctor (57.7% vs. 33.3%; AOR 2.2; 95% CI 1.6-3.1). CONCLUSIONS: Addressing issues of parent HL may be helpful in ameliorating barriers to care and promoting provider-parent partnership in care. PMID- 22321815 TI - Feasibility of initiating and sustaining registry-based immunization recall in private practices. AB - OBJECTIVE: To assess the feasibility of initiating and sustaining immunization recall by private practices, including the barriers and costs, using a statewide immunization information system (IIS). METHODS: Private practices in southeast Michigan were recruited in 2007 to perform IIS-based immunization recalls. Enrolled practices were provided with training and asked to conduct 4 recalls during the course of 12 months of children 19 to 35 months of age. Each practice recorded the time they spent performing recall-related activities; labor costs were estimated. Formative and summative evaluations with semistructured interviews were conducted to identify barriers. RESULTS: Of 97 eligible pediatric and family medicine practices, 44 declined to participate, 32 did not respond to repeated contacts, and 20 agreed to enroll in the study (21%). A total of 56 recalls were conducted during the study period, with 9 practices completing at least 4 recalls and 7 practices completing 1 to 3 recalls; 4 practices conducted no recalls. Common barriers reported included time constraints and executing all steps of the recalls. Practice costs per patient recalled ranged from $0.05 to more than $6 and were primarily driven by the type of personnel who performed recalls. The costs of creating a roster of current patients comprised nearly one half of total labor costs. CONCLUSIONS: Few private provider practices that we contacted were willing to participate in this study of IIS-based recall, and less than one-half of enrolled practices completed the desired 4 recall cycles in 12 months. Time constraints and other real-world problems should not be underestimated in determining the feasibility of practice-based immunization recall. Efforts to increase the use of a statewide IIS for recall in private practice settings should emphasize ongoing training and technical support to practice staff. Improved interoperability with electronic health record systems may foster practice-based recall by reducing the labor intensity of roster building and other recall activities. PMID- 22321816 TI - Diagnostic accuracy of magnetic resonance imaging for an acute pulmonary embolism: results of the 'IRM-EP' study. AB - BACKGROUND: Magnetic resonance imaging (MRI) has not been validated as an alternative diagnostic test to computed tomography angiography (CTA) in patients with suspicion of a pulmonary embolism (PE). OBJECTIVES: To evaluate performance of current MRI technology in diagnosing PE, in reference to a 64-detector CTA. PATIENTS/METHODS: Prospective investigation including 300 patients with a suspected PE, referred for CTA after assessment of clinical probability and D dimer testing. MRI protocol included unenhanced, perfusion and angiographic sequences. MRI results were interpreted by two independent readers, to evaluate inter-reader agreement. Sensitivity and specificity were evaluated globally and according to PE location and to clinical probability category. RESULTS: Of 300 enrolled patients, 274 were analyzed and 103 (37.5%) had a PE diagnosed by CTA. For patients with conclusive MRI results (72% for reader 1, 70% for reader 2), sensitivity and specificity were 84.5% (95% confidence interval [CI], 74.9-91.4%) and 99.1% (95% CI, 95.1-100.0%), respectively, for reader 1, and 78.7% (95% CI, 68.2-87.1%) and 100% (95% CI, 96.7-100.0%) for reader 2. After exclusion of inconclusive MRI results for both readers, inter-reader agreement was excellent (kappa value: 0.93, 95% CI: 0.88-0.99). Sensitivity was better for proximal (97.7 100%) than for segmental (68.0-91.7%) and sub-segmental (21.4-33.3%) PE (P < 0.0001). Sensitivity was similar for both readers within each clinical probability category. CONCLUSIONS: Current MRI technology demonstrates high specificity and high sensitivity for proximal PE, but still limited sensitivity for distal PE and 30% of inconclusive results. Although a positive result can aid in clinical decision making, MRI cannot be used as a stand-alone test to exclude PE. PMID- 22321817 TI - LRRC3B gene is frequently epigenetically inactivated in several epithelial malignancies and inhibits cell growth and replication. AB - Chromosome 3 specific NotI microarrays containing 180 NotI linking clones associated with 188 genes were hybridized to NotI representation probes prepared using matched tumor/normal samples from major epithelial cancers: breast (47 pairs), lung (40 pairs) cervical (43 pairs), kidney (34 pairs of clear cell renal cell carcinoma), colon (24 pairs), ovarian (25 pairs) and prostate (18 pairs). In all tested primary tumors (compared to normal controls) methylation and/or deletions was found. For the first time we showed that the gene LRRC3B was frequently methylated and/or deleted in breast carcinoma - 32% of samples, cervical - 35%, lung - 40%, renal - 35%, ovarian - 28%, colon - 33% and prostate cancer - 44%. To check these results bisulfite sequencing using cloned PCR products with representative two breast, one cervical, two renal, two ovarian and two colon cancer samples was performed. In all cases methylation was confirmed. Expression analysis using RT-qPCR showed that LRRC3B is strongly down-regulated at the latest stages of RCC and ovarian cancers. In addition we showed that LRRC3B exhibit strong cell growth inhibiting activity (more than 95%) in colony formation experiments in vitro in KRC/Y renal cell carcinoma line. All these data suggest that LRRC3B gene could be involved in the process of carcinogenesis as a tumor suppressor gene. PMID- 22321818 TI - Periodic 48 h feed withdrawal improves glucose tolerance in growing pigs by enhancing adipogenesis and lipogenesis. AB - BACKGROUND: Adipocyte numbers and peroxisome proliferators activated receptorgamma (PPARgamma) expression of retroperitoneal tissue increased while area under the curve (AUC) during the glucose tolerance test (GTT) was reduced in rats subjected to certain feed withdrawal (FW) regimens. Thus, using pigs as the experimental model, the hypothesis that FW regimens influence glucose tolerance by influencing fat cell function was evaluated with the objective of determining the effect of a single (FWx1; at age of 19 wk for 48 h) or periodic, multiple (FWx4; 24 h FW at 7 and 11 wk of age and 48 h FW at 15 and 19 wk of age) FW on AUC of glucose and insulin during the GTT relative to pigs that did not experience FW (Control). METHODS: Growth, body composition, adipocyte numbers, PPARgamma expression, lipogenic potential as glucose uptake into fat of adipocytes of varying diameter in omental (OM) and subcutaneous (SQ) fat as affected by FW regimens were determined in pigs initiated into the study at 5 wk of age and fed the same diet, ad libitum. RESULTS: Blood glucose concentrations for prior to and 120 min post glucose meal tended to be lower (p = 0.105 and 0.097, respectively) in pigs in FW treatments. In OM fat; cell numbers, glucose Universal14C [U14C] incorporation into fat and rate of incorporation per 104 cells was greatest for cells with diameters of 90-119 MUm. Pigs undergoing FWx4 tended to have greater (p = 0.0685; by 191%) number of adipocytes, increased (p = 0.0234) glucose U14C incorporation into adipocytes and greater (p = 0.0872) rate of glucose uptake into cells of 119-150 MUm diameter than of cells from control or FWx1 pigs. Subcutaneous adipocyte numbers in 22-60 and 61-90 MUm diameter ranges from pigs in FWx1 tended to be greater (p = 0.08 and 0.06, respectively) than for those in FWx4 treatment, yet PPARgamma expression and total cell number were not affected by treatment. CONCLUSIONS: Results suggest that FW regimens influence fat cell function or lipogenesis rather than number, affecting glucose metabolism and may have implications in drug-free control of metabolic syndrome symptoms. PMID- 22321819 TI - MicroRNAs and ovarian function. AB - MicroRNAs (miRNAs) are a class of small non-coding RNAs which function in gene regulation with an important role in cell proliferation, maturation, and activity. The regulatory role of these small RNA molecules has recently begun to be explored in ovarian cells, uncovering their influence on gonadal development, steroidogenesis, apoptosis, ovulation, and corpus luteum development. This emerging area of research has extended and reshaped our understanding on how ovarian function is regulated. Here, we review the current understanding of miRNA biogenesis, the role and mechanism that miRNAs play in post-transcriptional gene expression regulation, and specifically the current evidence of miRNA involvement in ovarian development and function. Future comprehensive understanding of the role of miRNAs in the ovary in both physiological and pathological conditions may offer new treatment strategies for infertility and other ovarian disorders. PMID- 22321820 TI - Body weight perception is associated with socio-economic status and current body weight in selected urban and rural South Indian school-going children. AB - OBJECTIVE: To evaluate the current and ideal body weight perceptions of schoolchildren in relation to their actual body weight and socio-economic status (SES). DESIGN: Baseline evaluation of schoolchildren from January 2008 to April 2008 as part of a 3-year longitudinal study. SETTING: City and non-city locations, Karnataka State, South India. SUBJECTS: Schoolchildren (n 1877) aged between 8 and 14 years. RESULTS: Girls, children of more educated parents and city dwellers were more likely to be overweight (P < 0.001). Younger children aged <10 years and those of lower SES were more likely to perceive themselves as underweight (adjusted OR = 1.63, 95 % CI 1.25, 2.11 and adjusted OR = 1.87, 95 % CI 1.32, 2.65). Underweight children were ten times more likely to overestimate their current weight status, while overweight children were four times more likely to underestimate it. The odds of children of lower SES underestimating their weight, as well as desiring a higher weight, were higher than those of higher-SES children. CONCLUSIONS: SES is associated with body weight perception. Underweight children are more likely to overestimate their weight status and overweight children more likely to underestimate it. PMID- 22321821 TI - What are the reasons for high turnover in nursing? A discussion of presumed causal factors and remedies. AB - Problems with high turnover in nursing and of maintaining adequate numbers of nurses to supply clinical staffing requirements have a long history and have therefore attracted a commensurate literature with time. An overview and discussion of the situation internationally, with an emphasis on Organisation for Economic Co-operation and Development (OECD) countries and the UK, finds that job satisfaction is often a consistent underlying determinant interacting with workplace factors and personal reasons in complex ways. Effective and adaptive retention strategies are required to meet and mitigate the problem as reasons for it may vary over time. Solutions must be flexible and targeted to meet the individual circumstances identified. PMID- 22321822 TI - Laryngotracheal reconstruction and cricotracheal resection in children: recent experience at Great Ormond Street Hospital. AB - BACKGROUND: Surgery for paediatric airway stenosis is constantly evolving. Surgery is the primary treatment modality via either an open or endoscopic approach. The objective of this study was to review the results of laryngotracheal reconstruction (LTR) and cricotracheal resection (CTR) procedures performed at Great Ormond Street Hospital over the past 10 years. METHODS: All patients who underwent open airway reconstruction surgery from January 2000 to December 2010 were included in this study. Patients treated entirely endoscopically were excluded. The data was collected using the electronic operating theatre database and the discharge summary database. RESULTS: Complete data was available for 199 patients who underwent open airway reconstruction from January 2000 to December 2010. The procedures included single stage LTR (57, 28.6%), two stage LTR (115, 57.7%), single-stage stomal reconstruction (14), single-stage CTR (8) and two-stage CTR (5). The diagnoses at the initial airway endoscopy were laryngeal web (22), subglottic stenosis (151), posterior glottic stenosis (9), suprastomal collapse (15), supraglottic stenosis (1) and tracheal stenosis (1). For those with subglottic stenosis, the stenosis was grade 1 in 1 patient, grade 2 in 26 patients, grade 3 in 117 patients and grade 4 in 6 patients. At the completion of intervention 175/199 (87.9%) patients reported improvement in their symptoms. Amongst the subglottic stenosis group, post LTR success was achieved in 100% with grade 1 stenosis, 92.3% with grade 2 stenosis, 88.1% in grade 3 stenosis and 83.3% in grade 4 stenosis. Of the two-stage LTR procedures, 100/115 (86.9%) had their tracheostomy removed and 15/115 (13.1%) have failed decannulation. Of the single-stage LTR group, 50/57 (87.7%) patients were better both on airway examination and symptomatically postoperatively. Of the single-stage stomal reconstruction group, 13/14 (92.8%) were better symptomatically and on airway examination. Patients who underwent single-stage CTR had a better airway on examination and were symptomatically improved in all cases (8/8). For the patients who underwent two stage CTR, the tracheostomy was removed in 3/5 (60%) and retained in 2/5 (40%). For the whole group, 15/199 (7.5%) patients underwent a revision LTR. On further analysis, revision LTR was required in 4/57 (7.1%) single-stage LTR, 9/115 (7.8%) two-stage LTR, 1/5 (20%) two-stage CTR and 1/8 (12.5%) single-stage CTR. In this study complications occurred in 13/199 (6.5%). CONCLUSIONS: Subglottic stenosis in children needs to be approached on the basis of the nature and severity of stenosis and the individual patient's general health. Good outcomes are achieved with both LTR and CTR. Good results are obtained both with single-stage and two-stage LTR, but restenosis remains a problem. An individual approach is required for treatment of paediatric airway stenosis to achieve good final outcomes. The overall success rate has increased only marginally in our institution over the last 20 years. PMID- 22321823 TI - Upper airway abnormalities detected in children using flexible bronchoscopy. AB - OBJECTIVES: Rapid anatomical evaluation is essential to establish the severity of cases with upper respiratory obstruction and to define the degree of respiratory distress. Detailed airway endoscopy is required in most patients, not only for diagnosis, but also to treat the condition. In this study, as two of the largest paediatric pulmonology centres in Turkey, we reviewed the data of our bronchoscopy patients, and aimed to document the upper airway abnormalities that we detected during these procedures. PATIENTS AND METHODS: A retrospective analysis was made of the records of 1076 paediatric cases with pulmonary/airway disease who had undergone flexible bronchoscopy between 2007 and 2011. RESULTS: Upper airway malacia disorders were the most common (79.6%, n=259) bronchoscopic findings detected in the patients. The other most common pathologies were laryngeal edema (12.9%, n=42), external tracheal compression (12.3%, n=40), subglottic stenosis (4.0%, n=13), tracheal stenosis (2.8%, n=9), and vocal cord paralysis/irregularity (2.8%, n=9). The mean duration of symptoms was shortest in patients with vocal cord paralysis, and longest in patients with tracheal nodules (p<0.001). CONCLUSION: Paediatricians should keep in mind the possibility of malacia disorders and other congenital and acquired upper airway abnormalities in children with chronic respiratory problems. Diagnosis of underlying diseases, as soon as possible, permits the withdrawal of antibiotics or antiasthmatic drugs often used unnecessarily for long periods to treat these children. PMID- 22321824 TI - Compound heterozygosity of the novel c.292C>T (p.R98W) and the c.35delG GJB2 mutations in postlingual, non-syndromic, sensorineural deafness. AB - OBJECTIVES: Connexins (Cxs) are membrane-spanning proteins that co-assemble into intercellular gap junction channels. Gap junction channels mediate electrical and biochemical communication between adjacent cells and play vital roles as mediators of intercellular molecular signaling. Cx-linked deafness highlights the key role of gap junctions in the physiological processes of hearing. Co localization of Cxs with the gap junction system in the inner ear suggests a role in cochlear electrolyte homeostasis. During auditory transduction, they are proposed to maintain membrane potentials by regulating the flow of potassium ions between the sensory epithelia of the inner ear. METHODS: Clinical and molecular genetic methods were employed in a Greek proband presenting with bilateral, postlingual, non-syndromic, sensorineural deafness. RESULTS: We detected a novel c.292C>T (p.R98W) mutation in compound heterozygosity with the c.35delG mutation in the GJB2 gene. CONCLUSION: Although mutations in the GJB2 gene usually cause prelingual, severe to profound deafness, compound heterozygosity of the novel c.292C>T (p.R98W) and the c.35delG GJB2 mutations appears to be the cause of postlingual, moderate, sensorineural deafness in our proband. PMID- 22321825 TI - An antifungal peptide from Phaseolus vulgaris cv. brown kidney bean. AB - A 5.4-kDa antifungal peptide, with an N-terminal sequence highly homologous to defensins and inhibitory activity against Mycosphaerella arachidicola (IC(50)= 3 MUM), Setospaeria turcica and Bipolaris maydis, was isolated from the seeds of Phaseolus vulgaris cv. brown kidney bean. The peptide was purified by employing a protocol that entailed adsorption on Affi-gel blue gel and Mono S and finally gel filtration on Superdex 75. The antifungal activity of the peptide against M. arachidicola was stable in the pH range 3-12 and in the temperature range 0 degrees C to 80 degrees C. There was a slight reduction of the antifungal activity at pH 2 and 13, and the activity was indiscernible at pH 0, 1, and 14. The activity at 90 degrees C and 100 degrees C was slightly diminished. Deposition of Congo red at the hyphal tips of M. arachidicola was induced by the peptide indicating inhibition of hyphal growth. The lack of antiproliferative activity of brown kidney bean antifungal peptide toward tumor cells, in contrast to the presence of such activity of other antifungal peptides, indicates that different domains are responsible for the antifungal and antiproliferative activities. PMID- 22321826 TI - 11beta-Hydroxysteroid dehydrogenase type 1: relevance of its modulation in the pathophysiology of obesity, the metabolic syndrome and type 2 diabetes mellitus. AB - Recent evidence strongly argues for a pathogenic role of glucocorticoids and 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in obesity and the metabolic syndrome, a cluster of risk factors for atherosclerotic cardiovascular disease and type 2 diabetes mellitus (T2DM) that includes insulin resistance (IR), dyslipidaemia, hypertension and visceral obesity. This has been partially prompted not only by the striking clinical resemblances between the metabolic syndrome and Cushing's syndrome (a state characterized by hypercortisolism that associates with metabolic syndrome components) but also from monogenic rodent models for the metabolic syndrome (e.g. the leptin-deficient ob/ob mouse or the leptin-resistant Zucker rat) that display overall increased secretion of glucocorticoids. However, systemic circulating glucocorticoids are not elevated in obese patients and/or patients with metabolic syndrome. The study of the role of 11beta-HSD system shed light on this conundrum, showing that local glucocorticoids are finely regulated in a tissue-specific manner at the pre receptor level. The system comprises two microsomal enzymes that either activate cortisone to cortisol (11beta-HSD1) or inactivate cortisol to cortisone (11beta HSD2). Transgenic rodent models, knockout (KO) for HSD11B1 or with HSD11B1 or HSD11B2 overexpression, specifically targeted to the liver or adipose tissue, have been developed and helped unravel the currently undisputable role of the enzymes in metabolic syndrome pathophysiology, in each of its isolated components and in their prevention. In the transgenic HSD11B1 overexpressing models, different features of the metabolic syndrome and obesity are replicated. HSD11B1 gene deficiency or HSD11B2 gene overexpression associates with improvements in the metabolic profile. In face of these demonstrations, research efforts are now being turned both into the inhibition of 11beta-HSD1 as a possible pharmacological target and into the role of dietary habits on the establishment or the prevention of the metabolic syndrome, obesity and T2DM through 11beta-HSD1 modulation. We intend to review and discuss 11beta-HSD1 and obesity, the metabolic syndrome and T2DM and to highlight the potential of its inhibition for therapeutic or prophylactic approaches in those metabolic diseases. PMID- 22321827 TI - Age-related accumulation of T cells with markers of relatively stronger autoreactivity leads to functional erosion of T cells. AB - BACKGROUND: Thymic involution is a prominent characteristic of an aging immune system. When thymic function is reduced/absent, the peripheral T cell pool is subject to the laws of peripheral T cell homeostasis that favor survival/expansion of T cell receptors with relatively higher functional avidity for self-peptide/MHC complexes. Due to difficulties in assessing the TCR avidity in polyclonal population of T cells, it is currently not known whether high avidity T cells preferentially survive in aging individuals, and what impact this might have on the function of the immune system and development of autoimmune diseases. RESULTS: The phenotype of T cells from aged mice (18-24 months) indicating functional TCR avidity (CD3 and CD5 expression) correlates with the level of preserved thymic function. In mice with moderate thymic output (> 30% of peripheral CD62L(hi) T cells), T cells displayed CD3(low)CD5(hi) phenotype characteristic for high functional avidity. In old mice with drastically low numbers of CD62L(hi) T cells reduced CD5 levels were found. After adult thymectomy, T cells of young mice developed CD3(low)CD5(hi) phenotype, followed by a CD3(low)CD5(low) phenotype. Spleens of old mice with the CD3(low)/CD5(hi) T cell phenotype displayed increased levels of IL-10 mRNA, and their T cells could be induced to secrete IL-10 in vitro. In contrast, downmodulation of CD5 was accompanied with reduced IL-10 expression and impaired anti-CD3 induced proliferation. Irrespective of the CD3/CD5 phenotype, reduced severity of experimental allergic myelitis occurred in old mice. In MTB TCRbeta transgenic mice that display globally elevated TCR avidity for self peptide/MHC, identical change patterns occurred, only at an accelerated pace. CONCLUSIONS: These findings suggest that age-associated dysfunctions of the immune system could in part be due to functional erosion of T cells devised to protect the hosts from the prolonged exposure to T cells with high-avidity for self. PMID- 22321828 TI - A jumbo problem: mapping the structure and functions of the nuclear pore complex. AB - Macromolecular assemblies can be intrinsically refractive to classical structural analysis, due to their size, complexity, plasticity and dynamic nature. One such assembly is the nuclear pore complex (NPC). The NPC is formed from ~450 copies of 30 different proteins, called nucleoporins, and is the sole mediator of exchange between the nucleus and the cytoplasm in eukaryotic cells. Despite significant progress, it has become increasingly clear that new approaches, integrating different sources of structural and functional data, will be needed to understand the functional biology of the NPC. Here, we discuss the latest approaches trying to address this challenge. PMID- 22321829 TI - Deconstructing the centriole: structure and number control. AB - Centrioles are very small microtubule-based organelles essential for centrosome, cilia and flagella assembly, which are involved in a variety of cellular and developmental processes. Although the centriole was first described almost a century ago, the knowledge on its assembly mechanism remains poor. In the past decade, forefront functional studies have provided important data on the different players involved in centriole biogenesis. Centriole research has now started to profit from highly sensitive structural, imaging, and biochemical techniques that are unveiling how those players contribute to assemble such a small and complex structure. We will review those studies and discuss how this field will increasingly benefit from the newborn and exciting era of super resolution analyses. PMID- 22321830 TI - Characterization and significance of adhesion and junction-related proteins in mouse ovarian follicles. AB - In the ovary, initiation of follicle growth is marked by cuboidalization of flattened granulosa cells (GCs). The regulation and cell biology of this shape change remains poorly understood. We propose that characterization of intercellular junctions and associated proteins is key to identifying as yet unknown regulators of this important transition. As GCs are conventionally described as epithelial cells, this study used mouse ovaries and isolated follicles to investigate epithelial junctional complexes (tight junctions [TJ], adherens junctions [AJ], and desmosomes) and associated molecules, as well as classic epithelial markers, by quantitative PCR and immunofluorescence. These junctions were further characterized using ultrastructural, calcium depletion and biotin tracer studies. Junctions observed by transmission electron microscopy between GCs and between GCs and oocyte were identified as AJs by expression of N cadherin and nectin 2 and by the lack of TJ and desmosome-associated proteins. Follicles were also permeable to biotin, confirming a lack of functional TJs. Surprisingly, GCs lacked all epithelial markers analyzed, including E-cadherin, cytokeratin 8, and zonula occludens (ZO)-1alpha+. Furthermore, vimentin was expressed by GCs, suggesting a more mesenchymal phenotype. Under calcium-free conditions, small follicles maintained oocyte-GC contact, confirming the importance of calcium-independent nectin at this stage. However, in primary and multilayered follicles, lack of calcium resulted in loss of contact between GCs and oocyte, showing that nectin alone cannot maintain attachment between these two cell types. Lack of classic markers suggests that GCs are not epithelial. Identification of AJs during GC cuboidalization highlights the importance of AJs in regulating initiation of follicle growth. PMID- 22321831 TI - It takes two to tango but four for the finale. PMID- 22321832 TI - Phosphatidylinositol 4-phosphate 5-kinase is indispensable for mouse spermatogenesis. AB - The lipid kinase phosphatidylinositol 4-phosphate 5-kinase (PIP5K) produces a versatile signaling phospholipid, phosphatidylinositol 4,5-bisphosphate. Three PIP5K isozymes, PIP5K1A, PIP5K1B, and PIP5K1C, have been identified in mammals so far. Although the functions of these three PIP5K isozymes have been extensively studied in vitro, the in vivo physiological roles of these PIP5K isozymes remain largely unknown. In this study, we examined the functions of PIP5K1A and PIP5K1B in spermatogenesis, using Pip5k1a-knockout (KO), Pip5k1b-KO, and Pip5k1a/Pip5k1b double (D)-KO mice. Pip5k1a-KO and D-KO males were subfertile and completely sterile, respectively. F-actin in the seminiferous epithelium was disorganized in the D-KO mice, although F-actin bundles at the apical ectoplasmic specialization was not affected. D-KO seminiferous tubules contained a greatly decreased number of elongated spermatids. Flagella of sperm from Pip5k1a-KO and D-KO mice remarkably underwent morphological change, whereas Pip5k1b-KO sperm were morphologically normal. Notably, the flagellar shape of D-KO sperm was more severely impaired than that of Pip5k1a-KO sperm. These results suggest that PIP5K1A and PIP5K1B may coordinately and/or redundantly function in the maintenance of sperm number and morphology during spermatogenesis. PMID- 22321833 TI - Heparin/heparan sulfate/CD44-v3 enhances cell migration in term placenta-derived immortalized human trophoblast cells. AB - The function of CD44-v3 and heparin/heparan sulfate (HS) signaling was investigated during trophoblast cell migration to identify their role in the renewal of syncytial layer damage caused by increased hemodynamic turbulence in the intervillous space and maintenance of syncytial integrity in pre-eclampsia. We evaluated the effect of heparin/HS/CD44-v3-mediated processes during scratch wound closure in monolayer immortalized human trophoblast cells derived from term placenta (TCL-1 cells). Western blot analysis showed that these cultured human trophoblast cells express the epidermal growth factor receptor and CD44-v3 but do not express syndecan 4. An in vitro scratch wound healing assay showed enhanced migration of trophoblast cells in a dose-dependent manner in the presence of heparin compared with controls when cultured under serum-free conditions. Conversely, an anti-CD44 function-blocking antibody and CD44 siRNA suppressed the migration of trophoblast cells in the presence of heparin in a similar scratch assay. Furthermore, both heparin treatment and in vitro scratch wounding induced the phosphorylation of p21-activated kinase 1 (PAK1), whereas the anti-CD44-v3 antibody suppressed the heparin-induced phosphorylation of PAK1 in trophoblast cells. These results indicate that heparin/HS/CD44-v3-mediated signaling, in the absence of growth factor networks, enhances the direct repair of the damaged trophoblast layer through the migration of trophoblast cells. This renewed cell coverage may lead to the maintenance of syncytiotrophoblast cell function and an associated reduction in pathogenic soluble factors derived from the damaged trophoblast cells. PMID- 22321834 TI - Mono-(2-ethylhexyl) phthalate (MEHP) promotes invasion and migration of human testicular embryonal carcinoma cells. AB - Testicular dysgenesis syndrome refers to a collection of diseases in men, including testicular cancer, that arise as a result of abnormal testicular development. Phthalates are a class of chemicals used widely in the production of plastic products and other consumer goods. Unfortunately, phthalate exposure has been linked to reproductive dysfunction and has been shown to adversely affect normal germ cell development. In this study, we show that mono-(2-ethylhexyl) phthalate (MEHP) induces matrix metalloproteinase 2 (MMP2) expression in testicular embryonal carcinoma NT2/D1 cells but has no significant effect on MMP9 expression. NT2/D1 cells also have higher levels of MYC expression following MEHP treatment. It is widely recognized that activation of MMP2 and MYC is tightly associated with tumor metastasis and tumor progression. Gelatin zymographic analysis indicates that MEHP strongly activates MMP2 in NT2/D1 cells. Addition of the MMP2-specific inhibitor SB-3CT inhibited MEHP-enhanced cell invasion and migration, demonstrating that MMP2 plays a functional role in promoting testicular embryonal carcinoma progression in response to MEHP exposure. Furthermore, we investigated genome-wide gene expression profiles of NT2/D1 cells following MEHP exposure at 0, 3, and 24 h. Microarray analysis and semiquantitative RT-PCR revealed that MEHP exposure primarily influenced genes in cell adhesion and transcription in NT2/D1 cells. Gap junction protein-alpha 1, vinculin, and inhibitor of DNA-binding protein-1 were significantly down regulated by MEHP treatment, while claudin-6 and beta 1-catenin expression levels were up-regulated. This study provides insight into mechanisms that may account for modulating testicular cancer progression following phthalate exposure. PMID- 22321835 TI - Cationic lipids containing cyclen and ammonium moieties as gene delivery vectors. AB - In this study, two novel cationic lipids containing protonated cyclen and quaternary ammonium moieties were designed and synthesized as non-viral gene delivery vectors. The structures of the two lipids differ in their hydrophobic region (cholesterol or diosgenin). Cationic liposomes were easily prepared from the lipids individually or from the mixtures of each cationic lipid and dioleoylphosphatidylethanolamine. Several studies including DLS, gel retardation assay, and ethidium bromide intercalation assay suggest that these amphiphilic molecules are able to bind and compact DNA into nanometer particles which can be used as non-viral gene delivery agents. Our results from in vitro transfection show that in association with dioleoylphosphatidylethanolamine, two cationic lipids can induce effective gene transfection in human embryonic kidney 293 cells, although the gene transfection efficiencies of two cationic lipids were found to be lower than that of lipofectamine 2000(TM) . Besides, different cytotoxicity was found for two lipoplexes. This study demonstrates that the title cationic lipids have large potential to be efficient non-viral gene vectors. PMID- 22321836 TI - [Correlation of transcutaneous oxygen challenge test and central venous oxygen saturation in septic shock patients]. AB - OBJECTIVE: To investigate the correlation of transcutaneous oxygen challenge test (OCT) [the degree of PtcO2 response to increased fractional inspired oxygen concentration (FiO2) of 1.0 is identified as transcutaneous OCT] and central venous oxygen saturation (ScvO2) in septic shock patients after resuscitation. METHODS: A total of 49 septic shock patients were prospectively studied. They underwent PtcO2 monitoring and OCT (a temporary increase of FiO2 for 10 min). Baseline central venous blood gases, baseline arterial blood gases and post-OCT arterial blood gases were examined. The parameters of PtcO2 index (baseline PtcO2/PaO2), tissue oxygen index (baseline PtcO2/FiO2), 10 min OCT value [(PtcO2 after 10 min on FiO2 of 1.0) minus (baseline PtcO2)], oxygen challenge index [(10 min OCT value)/(PaO2 on FiO2 1.0 minus baseline PaO2)] were calculated during OCT. The patients were divided into 2 groups according to ScvO2 values: normal ScvO2 group (ScvO2 >= 70%) versus low ScvO2 group (ScvO2 < 70%). The parametric differences of transcutaneous OCT were compared between two groups. RESULTS: (1) There was a significant correlation between baseline PtcO2 (r = 0.382, P = 0.007), tissue oxygen index (r = 0.355, P = 0.012), 10 min OCT value (r = 0.427, P = 0.002), oxygen challenge index (r = 0.5, P < 0.001) and ScvO2, but not with arterial blood lactate concentration; (2) there were 27 patients in the low ScvO2 group and 22 patients in the normal ScvO2 group. ScvO2 was significantly lower in the low ScvO2 group than in the normal ScvO2 group (61 +/- 8 vs 77 +/- 6, P < 0.05). No differences in age, severity score, vital signs, arterial blood lactate concentration, vasoactive drugs, PtcO2, PtcO2 index and tissue oxygen index were observed between these groups. Compared with those in the normal ScvO2 group, the patients in the low ScvO2 group had a lower 10 min OCT value and oxygen challenge index (P < 0.05); (3) the area under the receiver operating characteristic curve (ROC) for detecting the lower ScvO2 values was 0.621, 0.560, 0.589, 0.721 and 0.763 respectively according to baseline PtcO2, PtcO2 index, tissue oxygen index, 10 min OCT value and oxygen challenge index. The cutoff of 10 min OCT value was <= 57 mm Hg (1 mm Hg = 0.133 kPa) for detecting ScvO2 values under 70%, resulting in a sensitivity of 51.9% and a specificity of 95.5%. CONCLUSION: OCT may improve the diagnostic accuracy of PtcO2 in assessing the low ScvO2 values in septic shock patients after resuscitation. PMID- 22321837 TI - [Airway stenting with inhalation anesthesia in malignant airway stenosis or fistula under radiological guidance]. AB - OBJECTIVE: To assess the efficacy and safety of airway stenting with inhalation anesthesia under radiological guidance in the palliation of malignant tracheobronchial stenosis. METHODS: Between June 2001 and August 2010, 74 consecutive patients with malignant tracheobronchial stenosis were treated by the insertion of an ultraflex self-expandable metal stent with inhalation anesthesia under fluoroscopic guidance. RESULTS: All patients achieved obvious symptomatic relief. The outcomes were as follows: dyspnea (n = 2), long-term angina (n = 1), strong irritation cough (n = 2), hard phlegm (n = 3), clotting expectoration (n = 3), blood-tinged expectoration (n = 64), airway stent displacement (n = 1) and tracheoesophageal fistulas (n = 1). CONCLUSION: Performed with inhalation anesthesia under radiological guidance, tracheobronchial recanalization with a self-expandable metal stent is a safe and effective palliative treatment for malignant stenosis. PMID- 22321838 TI - [The clinic value of (18)F-FDG PET/CT imaging in differentiation of malignant from benign disease in lung]. AB - OBJECTIVE: To evaluate the clinic value of (18)F-FDG PET/CT imaging in differentiation of malignant from benign disease in lung. METHODS: 188 patients underwent (18)F-FDG 45 min early and 2 h delayed PET/CT imaging after intravenous injection of (18)F-FDG. The standardized uptake value (SUV) and retention index (RI) of region of interesting were calculated. The histological diagnosis or clinical findings in a 12 months follow-up period served as the standard of truth. RESULTS: In 114 patients with malignant disease and 74 patients with benign disease, the sensitivity, speciality and accuracy of (18)F-FDG PET/CT imaging in differentiation of malignant from benign lung nodules (diameter more than 10 mm) were 98.2%, 80.0%, and 96.6%, in mediastinal lymph nodes and were 95.7%, 41.7%, and 84.8%, respectively. The sensitivity of (18)F-FDG PET imaging for lung nodules (diameter less than 10 mm) was lower than CT. CONCLUSIONS: Integrated PET/CT imaging provides high sensitivity, specificity and reasonably high accuracy for lung cancer. PMID- 22321839 TI - [Effects of depressive disorder on monocytic expression of CD(40) and plasma IL-8 concentration in senile coronary heart disease patients]. AB - OBJECTIVE: To observe the monocytic expression of CD(40) and plasma IL-8 concentration in senile CHD (coronary heart disease) patients with depressive disorder and examine the effects of immunological factors in depressive disorder and CHD. METHODS: A total of 100 senile CHD patients (> 60 yr old) were divided into 3 group: control group (A, n = 30), depression score <= 20 & anxiety score <= 6; therapy group (B, n = 35), depression score >= 30 & anxiety score <= 6, psychological evaluations with HAMD (Hamilton depression rating scale) from Day 1 pre-operation to Day 7 post-operation; non-therapy group (C, n = 35), depression score >= 30 & anxiety score <= 6. They underwent the same operation: lumbar decompression & fusion, stripping of great saphenous vein and repair of indirect hernia. At Day 1 pre-operation and Day 7 post-operation, 2 ml venous blood was drawn for the detection of monocytic expression of CD(40) and plasma concentration of IL-8 (interleukin-8). RESULTS: Depressive value of Group B at post-operation was lower than that at pre-operation and Group C ((25.1 +/- 2.9) vs (33.2 +/- 1.4) & (34.2 +/- 0.8), P < 0.05); the pre-operative expression of CD(40) of Group A was lower than the other groups ((123 +/- 18) vs (197 +/- 23) & (204 +/- 26), P < 0.05). And Group B at post-operation was lower than Group C ((147 +/- 19) vs (212 +/- 18), P < 0.05); the pre-operative concentration of IL-8 was lowest in Group A ((85 +/- 16) ng/L vs (151 +/- 18) ng/L & (164 +/- 22) ng/L, P < 0.05). And Group B at post-operation was lower than Group C ((158 +/- 19) ng/L vs (197 +/- 24) ng/L, P < 0.05). There were significantly positive correlations between depression scores, the expression of CD(40) and the plasma concentration of IL-8. CONCLUSION: Depressive disorders elevate the monocytic expression of CD(40) and raise the plasma concentration of IL-8 in senile CHD patients. Some immunological factors may play a important role in depressive disorder and CHD. PMID- 22321840 TI - [Clinical features of ultra longitudinally extensive transverse myelitis]. AB - OBJECTIVE: To analyze the clinical features of ultra longitudinally extensive transverse myelitis (uLETM). METHODS: Four first-onset uLETM patients hospitalized during September 2009 and March 2011 were recruited and retrospectively analyzed for clinical and MRI (magnetic resonance imaging) features, as well as therapeutic profiles and prognoses. RESULTS: The male-to female ratio was 1:3 and the age-of-onset 29 - 33 years old. Extremity paralysis and intrinsic sphincter disorders were initially observed. The clinical manifestations include visual, motor, sense and intrinsic sphincter disorders caused by optic nerve and spinal cord lesions. Uric acid decreased in 3 cases. Seropositivity for autoimmune antibody spectrum and NMO-IgG (neuromyelitis optica immunoglobulin G) was found in some patients. Spinal MRI showed overall hypointense T1 and hyperintense T2 lesions in spinal cord with partial swelling and negative in brain MRI. Sjogren's syndrome associated with uLETM was diagnosed in 2 patients. Three cases improved after treatment with high-dose corticosteroids, intravenous immunoglobulin and other immunosuppressive agents. One patient died. CONCLUSION: uLETM is commonly found in young women. Spinal cord is frequently affected. And it may occur concurrently with optical abnormalities and other autoimmune diseases. Intracranial parenchyma is rarely affected. The therapy of corticosteroids is recommended. PMID- 22321841 TI - [Treatment of instability of patellofemoral joint through athroscopic repair of medial patellofemoral ligament for adolescents with epiphyseal non-closure by allogenic tendon]. AB - OBJECTIVE: To explore the efficacy of arthroscopic repair of medial patellofemoral ligament (MPFL) for adolescents with epiphyseal non-closure by allogenic tendon in the treatment of instable patellofemoral joint. METHODS: There were a total of 38 cases including 61 knees with patellofemoral instability from June 2008 to January 2010 at our department. They were diagnosed according to the history of illness, apprehension test and tangential position radiograph in patellofemoral joint. RESULTS: A total of 33 patients with 52 knees were followed up for an average of 12 months (range: 8 - 19). All apprehension tests were negative. No recurrent displacement was found. The pre-operative Lysholm score of 75.5 +/- 4.7 increased to 91.1 +/- 5.7. There was significant difference. CONCLUSION: Arthroscope-assisted allograft reconstruction of medial patellofemoral ligament tendon is both mini-invasive and reliable for the treatment of epiphyseal non-closure adolescents with traumatic patellofemoral instability. PMID- 22321842 TI - [Symptom-based relationship between gastroesophageal reflux disease and laryngopharyngeal reflux disease]. AB - OBJECTIVE: To explore the relationship between gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux disease (LPRD) based on symptoms. METHODS: A total of 1090 patients undergoing upper digestive tract motility test were invited to complete the surveys of reflux disease questionnaire and reflux symptom index from August 2007 to October 2010. And 895 responders provided valid answers. There were 474 females and 421 males. RESULTS: Among 895 responders, 351 patients had neither, 218 suffered both conditions, 237 were diagnosed as GERD alone and 89 LPRD alone. No difference was found in age (P = 0.383)or gender ratio (P = 0.227). In 455 GERD patients, there were 218 LPRD cases (47.9%). In 307 LPRD patients, 218 (71.0%) had concurrent GERD. In GERD patients, the frequency and degree of feeling of stomach content reflux into mouth were correlated with RSI (r = 0.115, 0.141, P = 0.007, 0.001). CONCLUSION: GERD and LPRD may coexist or occur alone. Because of a high concurrent ratio of LPRD in GERD, the treatment strategy of GERD should be modified accordingly. In GERD patients, the feeling of stomach content reflux into mouth may suggest a possibility of LPRD. PMID- 22321843 TI - [Short-term efficacies of Fufangkushen Injection plus chemotherapy in patients with solid tumors: a meta-analysis of randomized trials]. AB - OBJECTIVE: To evaluate the short-term efficacies of Fufangkushen Injection plus chemotherapy in patients with solid tumors. METHODS: A comprehensive retrieval of the relevant literatures was performed by searching major biomedical databases of Medline, Embase, the Cochrane Library, Chinese Biomedical Literature Database (CBM), China Academic Journals Full-text Database (CNKI), Chinese Medical Current Contents (CMCC) and China Online Journals (Wangfang). And study selection and assessment, data collection and analysis were undertaken by two reviewers according to the Cochrane Handbook for Systematic Reviews of Interventions. Short term efficacies were analyzed in each corresponding subgroup according to the type of tumor. Statistical analysis was performed by Review Manager Software 4.2 (RevMan 4.2). RESULTS: Overall there were 33 studies of randomized controlled trials with a total of 2897 patients. All were of excellent homogeneity. The four subgroup-analyses (colorectal cancer, NSCLC (non-small cell lung cancer), breast cancer and gastric cancer) were performed with a fixed-effects model. The results of meta-analysis demonstrated that the short-term efficacies in patients with colorectal cancer, NSCLC and breast cancer receiving Fufangkushen Injection plus chemotherapy were significantly better than for those receiving chemotherapy alone (OR = 2.48 (1.59, 3.90), Z = 3.94, P < 0.0001; OR = 1.43 (1.20, 1.71), Z = 3.97, P = 0.0001; OR = 2.06 (1.28, 3.34), Z = 2.96, P = 0.003, respectively). However the patients with gastric cancer on combined chemotherapy were not significantly different from those on chemotherapy alone (OR = 1.25 (0.73, 2.13), Z = 0.81, P = 0.46). CONCLUSION: Fufangkushen Injection might improve the efficacies of chemotherapy in patients with colorectal cancer, NSCLC and breast cancer. Further large-scale multicenter and better designed studies are warranted to offer more convincing evidences. PMID- 22321844 TI - [Human stool vimentin, oncostatin M receptor and tissue factor pathway inhibitor 2 gene methylation analysis for the detection of colorectal neoplasms]. AB - OBJECTIVE: To explore the feasibility of detecting vimentin, oncostatin M receptor (OMSR) and tissue factor pathway inhibitor 2 (TFPI2) gene methylation status in stool samples as a noninvasive screening tool for colorectal cancer and precancerous lesions. METHODS: Stool samples were collected from 60 patients with colorectal cancer, 17 patients with adenoma and 30 normal volunteers. And fecal DNA was extracted and vimentin, OMSR and TFPI2 gene methylation status was analyzed by methylation-specific polymerase chain reaction (MSP). RESULTS: The methylated vimentin, OMSR and TFPI2 was detected in 53.3% (32/60), 68.3% (41/60) and 75.0% (45/60) of colorectal cancer, and 5, 7 and 11 cases of colorectal adenoma respectively. The sensitivities of combined study, using three markers for the detection of colorectal cancer and colorectal adenomas, were 86.7% (26/30) and 76.5% (13/17) respectively. And the specificity was 86.7% (52/60). CONCLUSION: As a feasible epigenetic marker, promoter hypermethylation for vimentin, OMSR and TFPI2 in stool samples is a sensitive, specific and noninvasive alternative for colorectal cancer screening. PMID- 22321845 TI - [Comparison of clinical outcomes between laparoscopic-assisted and hand-assisted laparoscopic operations in colorectal cancer]. AB - OBJECTIVE: To compare the clinical outcomes of laparoscopic-assisted versus hand assisted laparoscopic radical operations in colorectal cancer and evaluate the safety and indications of hand-assisted laparoscopic operations. METHODS: A total of 64 consecutive colorectal cancer patients enrolled from November 2009 to December 2011 at our hospital were randomly and prospectively divided into 2 groups: hand-assisted laparoscopic operation (HALS) (n = 32) and laparoscopic assisted operation (n = 32). And such clinicopathologic features as safety, operative curability and postoperative recovery were compared between two groups. RESULTS: Neither death nor conversion-to-open-surgery was reported among all patients. There were no statistical differences in such clinicopathologic features as age, gender, body mass index, mass size and location (all P > 0.05). There were statistically a shorter operation time [(127 +/- 31) min vs (184 +/- 71) min, P = 0.022] and a smaller number of Trocar (2.4 vs 5.0, P = 0.015) in the HALS group. However, the laparoscopic-assisted group had a lesser volume of blood loss [(82 +/- 31) ml vs (150 +/- 42) ml, P = 0.008] and a smaller postoperative 48 h drainage flow [(170 +/- 52) ml vs (208 +/- 58) ml, P = 0.020]. Moreover, no statistical differences existed in the length of bowel resection [(19 +/- 5) cm vs (18 +/- 4) cm], amount of lymph nodes dissection (16 +/- 4 vs 16 +/- 3), postoperative complications [12.5% (4/32) vs 25.0% (8/32)], time of intestinal function recovery [(1.7 +/- 0.9) d vs (1.8 +/- 0.7) d], time of semifluid tolerance [(2.9 +/- 1.3) vs (2.8 +/- 1.2) d], hospitalization expenses [(4.8 +/- 0.6) 10 000 yuan vs (4.9 +/- 0.4) 10 000 yuan] and postoperative hospital stay [(6.7 +/- 2.3) d vs (6.6 +/- 2.3) d] (all P > 0.05). CONCLUSION: HALS is both safe and efficacious for colorectal cancer patients. PMID- 22321846 TI - [Role of modified external ventricular drainage in the management of children with tuberculous meningitis hydrocephalus]. AB - OBJECTIVE: To explore the role of modified external ventricular drainage (mEVD) in the treatment of tuberculous meningitis obstructive hydrocephalus in children. METHODS: The records were retrospectively reviewed for 30 pediatric patients of tuberculous meningitis with hydrocephalus (TBMH) undergoing surgery between January 2007 and December 2010. The procedures included ventricular abdomen subcutaneous drainage (mEVD) (n = 6), Ommaya reservoir (n = 9) and ventriculoperitoneal shunt (VPS) (n = 15). White cell count and protein content of cerebrospinal fluid were measured repeatedly. And their clinical outcomes were assessed at 6 months post-operation. RESULTS: External drainage was extracted for 4 of 6 TBMH patients after 4 - 6 months of mEVD. Neither intracranial infections nor serious postoperative complications occurred. Two of 6 TBMH received VPS substituting for mEVD. No statistically significant difference in white cell count, protein content of cerebrospinal fluid and outcome was found between the mEVD and VPS groups. CONCLUSION: Ventricular abdomen subcutaneous drainage is both safe and efficacious in the management of children with tuberculous meningitis hydrocephalus. This approach may avoid possible complications and long term indwelling shunt so that it is worthy of further clinical application. PMID- 22321847 TI - [Endoscopic microvacular decompression for trigeminal neuralgia]. AB - OBJECTIVE: To explore the feasibility, operating technique and precautions of endoscopic microvascular decompression for trigeminal neuralgia. METHODS: A retrospective analysis was conducted for 21 patients with primary trigeminal neuralgia. All underwent neuroendoscopic microvascular decompression for trigeminal nerves. RESULTS: The pains disappeared upon awaking post-anesthesia in 19 patients. In 2 patients, pains became significantly alleviated and disappeared after taking carbamazepine for 1 - 3 months. No patient suffered the injuries of trigeminal nerve and other cranial nerves. None had cerebellum edema or death. During the follow-up period, there was no recurrence of pains. CONCLUSION: Neuroendoscopic surgery may accomplish microvascular decompression for trigeminal nerve independently. As a minimally invasive and effective technique, it offers a clearer vision of local anatomy and decreases the probability of damaging nerves and vessels. There is no need for pulling cerebellum. It brings minimal damage to normal brain tissue compared with microsurgery. Further popularization is warranted. PMID- 22321848 TI - [Expressions and clinical significance of urokinase-type plasminogen activator and its receptor in vulvar tissues]. AB - OBJECTIVE: To explore the expressions of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in vulvar tissues and elucidate the patterns. METHODS: Thirty cases of vulvar neoplasms, 30 vulvar intraepithelial neoplasia (VIN) and 30 cases of normal epithelial tissue were harvested. And the expressions of uPA and uPAR in paraffin-embedded tissues were detected by immunohistochemistry. And the differential expressions of various vulvar tissues were observed. And the differences were compared in clinical stage and lymph node metastasis. RESULTS: (1) The expressions of uPA and uPAR in normal tissues (0.422 +/- 0.022, 0.431 +/- 0.027), vulvar intraepithelial neoplasia (VIN) (0.462 +/- 0.018, 0.467 +/- 0.015) and vulvar neoplasms (0.508 +/- 0.020, 0.510 +/- 0.020) were significantly different (P < 0.01). (2) The expressions of uPA and uPAR in vulvar tissue significantly increased with a rising stage-level (P < 0.05). (3) Compared with those without lymph node metastasis, the patients with lymph node metastasis had significantly higher expressions of uPA and uPAR in vulvar tissue (P < 0.05). CONCLUSION: Thus uPA and uPAR play an important role in the development process of vulvar neoplasms with an elevated expression in normal vulvar tissue, VIN and vulvar neoplasms. The invasiveness and prognosis of vulvar neoplasms may be evaluated through detecting the tissue expressions of uPA and uPAR. PMID- 22321849 TI - [Effect of siRNA silenced human tissue factor gene on hepatocellular carcinoma cell invasion and metastasis]. AB - OBJECTIVE: To study the effect of tissue factor (TF) on human hepatocellular carcinoma cells when their inner TF gene was knocked down by RNA interference. METHODS: The eukaryotic expression vector bearing siRNA sequence that targeted at TF gene was transfected into human hepatocellular carcinoma cell line HepG2. RT PCR and Western blot were used to detect the changes of TF gene expression. Transwell invasion assay invitro were used to show the invasive ability of HepG2 cells with transfected pGPU6/GFP/Neo-TFsiRNA. RESULTS: RT-PCR and Western blot analysis showed that HepG2 cells with pGPU6/GFP/Neo-TFsiRNA transfected decreased the endogenous TF gene expression. Correspondingly the mean invading cells was 14 +/- 10 for pGPU6/GFP/Neo-TFsiRNA transfection and 128 +/- 18 for the NCsiRNA transfection, respectively by the Transwell invasion test in vitro (P < 0.05). The results indicated that the invasive ability of the HepG2 cells with pGPU6/GFP/Neo-TFsiRNA transfected decreased obviously. CONCLUSIONS: TF is involved in the progression of hepatocellular carcinoma and inhibiting the expression of TF can decrease the invasion and metastasis ability of tumor cell in vitro. PMID- 22321850 TI - [Effects of Ginkgo biloba extract on the expression of eNOS and the release of NO in mesenteric arterioles of senile rats]. AB - OBJECTIVE: To investigate the effects of Ginkgo biloba extract (GBE) on the expression of endothelial nitric oxide synthase (eNOS) and the release of nitric oxide (NO) in mesenteric arterioles of aging rats. METHODS: (1) Cytologic experiment:human umbilical vein endothelial cells (HUVEC) were randomly divided into 3 groups: control group, NG-nitro-L-arginine methyl ester (L-NAME) group and GBE group. L-NAME group: 100 umol/L L-NAME was added into HUNEC for a 48-hour incubation. GBE group: After HUVEC was exposed to 100 umol/L L-NAME for 24 hours, 20 g/L GBE was added for another 24-hour co-incubation. Then the expression of eNOS protein was observed in each group. (2) Animal experiment: Thirty-two 24 month-old male SD rats were randomly divided into normal control group (n = 8) and GBE group (n = 24). The GBE group was further divided into 3 groups receiving an orally dosed GBE for 3, 5, 7 days respectively. Afterward the diameter of first-order mesenteric arteriole was measured under the pressures of 20, 40, 60, 80, 100, 120, 140 mm Hg (1 mm Hg = 0.133 kPa) and the elasticity of blood vessels calculated. The release of NO, the expression of eNOS protein and its mRNA in mesenteric arterioles stimulated by the same shear stress (15 dyn/cm(2)) were evaluated respectively. RESULTS: (1) Cytological studies indicated that the expression of eNOS protein of the L-NAME group was significantly lower than those of the control and GBE groups (0.57 +/- 0.06 vs 0.96 +/- 0.05, 0.81 +/- 0.09, both P < 0.01). (2) After the dosing of GBE for 3, 5, 7 days, the release of NO was significantly higher than that of the control group [(8.01 +/- 0.24, 12.11 +/ 0.78, 14.72 +/- 0.70 vs 5.83 +/- 0.75) pmol*mm(-2)*min(-1), all P < 0.05]; the expressions of eNOS protein were significantly higher than those of the control group (0.59 +/- 0.20, 0.86 +/- 0.02, 1.09 +/- 0.13 vs 0.41 +/- 0.16, all P < 0.05). And GBE was highest at Day 7; the expression levels of eNOS mRNA were significantly higher than those of the control group (0.79 +/- 0.04, 0.85 +/- 0.07, 0.99 +/- 0.03 vs 0.58 +/- 0.05, all P < 0.05). And GBE was also highest at Day 7. CONCLUSION: GBE can improve vascular flexibility through increasing the expression of eNOS and the release of NO, protecting the functions of blood vessels. PMID- 22321851 TI - [Effect of anticoagulation and thrombolysis on circulation endothelial cells and endothelial function after acute inferior vena cava thrombosis in rats]. AB - OBJECTIVE: To explore the functions and adhesive properties of circulating endothelial cells after acute thrombosis in rats. METHODS: The inferior caval venous thrombosis model were treated with heparin (n = 45), urokinase (n = 45) and a combination of heparin and urokinase (n = 45) respectively. The sham group was treated similarly (n = 30). The thrombosed caval veins were harvested at Days 1, 3, 7, 14 and 28 post-thrombosis. Structural integrity and intimal hyperplasia were observed by light microscope. Scanning electron microscopy was used to assess the damage of endothelial cells in inferior caval vein wall. The level of thrombotic adhesion was measured in different phases. At Day 28, endothelial cell layer was observed under scanning electron microscope. Measurements were taken for circulating endothelial cells count, CEPC (circulating endothelial progenitor cell) count and CEPC adhesive capacity. RESULTS: The adhesion to caval vein wall was lower in groups B and C than that in group A at Day 3 post-thrombosis (all P < 0.01). The endothelial damage in group A was more serious than groups B and C at Day 7 (P < 0.05). And the endothelial damage was less severe in group C at Day 28 (P < 0.05). For the rats in A, B, C, SH groups, the numbers of circulating endothelial cell [(6.3 +/- 2.2)*10(6), (4.76 +/- 3.1)*10(6), (1.9 +/- 0.8)*10(6), (0.91 +/- 0.3)*10(6)], CEPC count (18.9 +/- 5.33, 37.4 +/- 6.0, 55.4 +/- 8.0, 64.1 +/- 3.2) and CEPC adhesion (9.6 +/- 2.9, 17.5 +/- 3.2, 22.1 +/- 4.4, 28.3 +/ 2.0) increased successively. There was statistical significance. CONCLUSION: A combination of heparin and urokinase for the treatment of acute inferior caval venous thrombosis may effectively maintain the endothelial integrity of vein wall and decrease the fibroblast proliferation of thrombosed vein. Adhesion to caval vein wall is relatively lower during an early post-thrombotic period. PMID- 22321852 TI - [Development of an intervertebral disc organ culture model and its clinical significance]. AB - OBJECTIVE: To develop an in vivo intervertebral disc organ culture model for a physiological environment and evaluate its clinical significance. METHODS: Murine functional spine units (FSUs) were isolated from 10-week-old mouse lumbar spines. FSUs consisted of two vertebrae surrounding one disc. Murine FSUs were cultured in medium and different concentrations of bupivacaine for different periods. Histological change and cell viability within intervertebral disc tissue were assessed by histological staining and MTT (3-(4,5-cimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assay. RESULTS: Murine disc organs cultured for up to 4 weeks showed minimal changes in tissue histology and cell viability. A 1 hour incubation in 0.25% bupivacaine resulted in about 25% cell death while 0.5% bupivacaine exposure yielded 60% cell death over the same time. CONCLUSION: Murine intervertebral disc maintains the integrity of tissue structures and cell functions for an ex vivo 4-week culture. And the exposure to bupivacaine dramatically decreases cell viability in a dose-dependent manner. PMID- 22321853 TI - A resident perspective on increasing duty-hour limitations. PMID- 22321854 TI - Re: "Colon preparation and surgical site infection". PMID- 22321855 TI - Positive feedback induced memory effect in ischemic preconditioning. AB - The memory of ischemic preconditioning remains a great mystery. Brief preconditioning (several sequential regional ischemia/reperfusion in minutes) can induce a two-phase protection that lasts up to 3 days. Thus comes the so-called memory of preconditioning. This memory effect has been attributed to a feed forward signaling cascade. But recent experimental observations suggest that intra-mitochondrial positive feedback may be responsible for sustaining the protective effect. The link between positive feedback and memory is yet to be determined. In this study, we used a mathematical model to describe the way in which positive feedback induces memory in the first window of cardioprotection, and we derived an explicit relationship between the memory duration and the strength of the positive feedback. Our major findings are: (1) that positive feedback relying on a hysteresis response provides an effective way of prolonging protection up to any length; and (2) that the stronger the positive feedback, the longer the memory duration. Furthermore, compared with the feed-forward signaling cascade, positive feedback may be more favored by natural systems because of its robustness and high efficiency. The mechanisms described in this study have important implications for developments of experimental approaches as well as therapeutic strategies. PMID- 22321856 TI - Modifying Fe3O4 nanoparticles with humic acid for removal of Rhodamine B in water. AB - Humic acid (HA) modifying Fe(3)O(4) nanoparticles (Fe(3)O(4)/HA) was developed for removal of Rhodamine B from water. Fe(3)O(4)/HA was prepared by a coprecipitation procedure with cheap and environmentally friendly iron salts and HA. TEM images revealed the Fe(3)O(4)/HA (with ~ 10 nm Fe(3)O(4) cores) were aggregated as aqueous suspensions. With a saturation magnetization of 61.2 emu/g, the Fe(3)O(4)/HA could be simply recovered from water with magnetic separations at low magnetic field gradients within a few minutes. Sorption of the Rhodamine B to Fe(3)O(4)/HA reached equilibrium in less than 15 min, and agreed well to the Langmuir adsorption model with maximum adsorption capacities of 161.8 mg/g. The Fe(3)O(4)/HA was able to remove over 98.5% of Rhodamin B in water at optimized pH. PMID- 22321857 TI - A green strategy for desorption of trihalomethanes adsorbed by humin and reuse of the fixed bed column. AB - The objective of the present work was to develop a thermal desorption method for the removal of trihalomethanes (THM) adsorbed by humin, followed by multiple recycling of the fixed bed column in order to avoid excessive consumption of materials and reduce operating costs. The results obtained for adsorption on a fixed bed column confirmed the effectiveness of humin as an adsorbent, extracting between 45.9% and 90.1% of the total THM (TTHM). In none of the tests was the column fully saturated after 10h. Experiments involving thermal desorption were used to evaluate the potential of the technique for column regeneration. The adsorptive capacity of the humin bed increased significantly (p<0.05) between the first and fifth desorption cycle, by 18.9%, 18.1%, 24.2%, 20.2% and 24.2% for CHBr(3), CHBr(2)Cl, CHBrCl(2), CHCl(3) and TTHM, respectively. PMID- 22321858 TI - Adsorption of sulfamethoxazole on biochar and its impact on reclaimed water irrigation. AB - Reclaimed water irrigation can satisfy increasing water demand, but it may also introduce pharmaceutical contaminants into the soil and groundwater environment. In this work, a range of laboratory experiments were conducted to test whether biochar can be amended in soils to enhance removal of sulfamethoxazole (SMX) from reclaimed water. Eight types of biochar were tested in laboratory sorption experiments yielding solid-water distribution coefficients (K(d)) of 2-104 L/kg. Two types of biochar with relatively high K(d) were used in column leaching experiments to assess their effect on reclaimed water SMX transport through soils. Only about 2-14% of the SMX was transported through biochar-amended soils, while 60% was found in the leachate of the unamended soils. Toxicity characteristic leaching experiments confirmed that the mobility and bioavailability of SMX in biochar-amended soils were lower than that of unamended soils. However, biochar with high accumulations of SMX was still found to inhibit the growth of the bacteria compared to biochar with less SMX which showed no effects. Thus, biochar with very high pharmaceutical sorption abilities may find use as a low-cost alternative sorbent for treating wastewater plant effluent, but should be used with caution as an amendment to soils irrigated with reclaimed water or waste water. PMID- 22321860 TI - [Treatment alternatives in massive hemorrhage]. AB - Massive hemorrhage is the main cause of mortality and morbidity in trauma patients, and is one of the most important causes in any patient following major surgery. Conventional treatment consists of volume replacement, including the transfusion of blood products, so that tissue perfusion and oxygenation may be maintained. Associated hypothermia, acidosis and coagulopathy is a lethal triad. This review focuses on the latest therapeutic management of massive hemorrhage. The authors advocate the use of crystalloids as per protocol (controlled volumes) in order to achieve a systolic blood pressure of 85mmHg. The administration of the three blood products (red cells, plasma, and platelets) should be on a 1:1:1 basis. Where possible, this in turn should be guided by thromboelastography performed at point of care near the patient. Coagulopathy can occur early and late. With the exception of tranexamic acid, the cost-benefit relationships of the hemostatic agents, such as fibrinogen, prothrombin complex, and recombinant F VII, are subject to discussion. PMID- 22321859 TI - Microbial biosafety of pilot-scale bioreactor treating MTBE and TBA-contaminated drinking water supply. AB - A pilot-scale sand-based fluidized bed bioreactor (FBBR) was utilized to treat both methyl tert-butyl ether (MTBE) and tert-butyl alcohol (TBA) from a contaminated aquifer. To evaluate the potential for re-use of the treated water, we tested for a panel of water quality indicator microorganisms and potential waterborne pathogens including total coliforms, Escherichia coli, Salmonella and Shigella spp., Campylobacter jejuni, Aeromonas hydrophila, Legionella pneumophila, Vibrio cholerae, Yersinia enterocolytica and Mycobacterium avium in both influent and treated waters from the bioreactor. Total bacteria decreased during FBBR treatment. E. coli, Salmonella and Shigella spp., C. jejuni, V. cholerae, Y. enterocolytica and M. avium were not detected in aquifer water or bioreactor treated water samples. For those pathogens detected, including total coliforms, L. pneumophila and A. hydrophila, numbers were usually lower in treated water than influent samples, suggesting removal during treatment. The detection of particular bacterial species reflected their presence or absence in the influent waters. PMID- 22321861 TI - Ultrasound evaluation of fetal brain dysfunction based on behavioral patterns. AB - To identify fetuses at high risk of poor neurological outcomes using a novel ultrasound evaluation system. We assessed an ultrasound evaluation system based on our previous findings, consisting of screening for decreased or lack of fetal movements, abnormal patterns of fetal heart rate, congenital CNS malformations, polyhydramnios of unknown cause, and a "brief ultrasound evaluation" of fetal brain functions, including movement of extremities, breathing movements, ultradian rhythm, REM period, and NREM period. We then assessed the correlation between fetal brain functions and neurological outcomes in infancy (MR, CP, and low Developmental Quotient). During screening, we prospectively evaluated 4978 fetuses receiving prenatal and intrapartum management between January 2000 and December 2009 in our hospital that were later delivered between 32 and 41 weeks' gestation and identified 93 cases as suspicious for impairment. Of the 93 fetuses, 26 underwent the second step of brief ultrasound examination at 35-40 weeks' gestation. Our findings revealed that this method was adequately sensitive (80%) and specific (88%) in identifying neurological impairment. We concluded that this method was mainly useful in the clinical setting for establishing the first indication for fetal CNS examination for functional impairment, rendering it suitable for clinical application. PMID- 22321862 TI - Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders. AB - BACKGROUND: The European Network of Rare Bleeding Disorders (EN-RBD) was established to bridge the gap between knowledge and practise in the care of patients with RBDs. OBJECTIVES: To explore the relationship between coagulation factor activity level and bleeding severity in patients with RBDs. PATIENTS/METHODS: Cross-sectional study using data from 489 patients registered in the EN-RBD. Coagulation factor activity levels were retrieved. Clinical bleeding episodes were classified into four categories according to severity. RESULTS: The mean age of patients at data collection was 31 years (range, 7 months to 95 years), with an equal sex distribution. On linear regression analysis, there was a strong association between coagulation factor activity level and clinical bleeding severity for fibrinogen, factor (F) X, FXIII, and combined FV and FVIII deficiencies. A weaker association was present for FV and FVII deficiencies. There was no association between coagulation factor activity level and clinical bleeding severity for FXI. The coagulation factor activity levels that were necessary for patients to remain asymptomatic were: fibrinogen, > 100 mg dL(-1); FV, 12 U dL(-1); combined FV + VIII, 43 U dL(-1); FVII, 25 U dL( 1); FX, 56 U dL(-1) ; FXI, 26 U dL(-1); FXIII, 31 U dL(-1). Moreover, coagulation factor activity levels that corresponded with Grade III bleeding were: undetectable levels for fibrinogen, FV and FXIII, < 15 U dL(-1) for combined FV + VIII; < 8 U dL(-1) for FVI; < 10 U dL(-1) for FX; and < 25 U dL(-1) for FXI. CONCLUSIONS: There is a heterogeneous association between coagulation factor activity level and clinical bleeding severity in different RBDs. A strong association is only observed in fibrinogen, FX and FXIII deficiencies. PMID- 22321863 TI - Statistical analysis and mapping of the Unified Parkinson's Disease Rating Scale to Hoehn and Yahr staging. PMID- 22321864 TI - Boxing and Parkinson disease: a link or a myth? An 18F-FDOPA PET/CT study in retired Thai traditional boxers. PMID- 22321865 TI - 123I-MIBG myocardial scintigraphy for differentiating Parkinson's disease from other neurodegenerative parkinsonism: a systematic review and meta-analysis. AB - OBJECTIVES: Differential diagnosis of Parkinson's disease (PD) and other neurodegenerative parkinsonism by clinical consensus criteria and diagnostic imaging is often difficult. (123)I-meta-iodobenzylguanidine ((123)I-MIBG) myocardial scintigraphy is a useful imaging tool for differentiating PD from other parkinsonism. The purpose of the present study is to systematically review and perform a meta-analysis of studies on the diagnostic performance of (123)I MIBG myocardial scintigraphy for the differential diagnosis of PD and other neurodegenerative parkinsonism, specifically multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration. METHODS: A computer literature search of the PubMED/MEDLINE database was conducted to find relevant published articles on (123)I-MIBG myocardial scintigraphy for the differential diagnosis of PD and other neurodegenerative parkinsonism. We used the bivariate random-effects model to obtain the pooled estimates of the sensitivity and specificity and the corresponding 95% confidence intervals. RESULTS: Thirteen studies comprising 845 patients including 625 PD and 220 other neurodegenerative parkinsonism were analyzed. The pooled sensitivity and specificity to differentiate PD from other neurodegenerative parkinsonism by the early heart-to-mediastinum (H/M) ratio were 82.6% and 89.2%, respectively, and those by the delayed H/M ratio were 89.7% and 82.6%, respectively. When PD was limited to early stage (Hoehn-Yahr stage 1 or 2), the pooled sensitivity and specificity by the delayed H/M ratio were 94.1% and 80.2%, respectively. CONCLUSIONS: The present meta-analysis confirmed high sensitivity and specificity of (123)I-MIBG myocardial scintigraphy for differentiating PD from other neurodegenerative parkinsonism in both early and delayed imaging phases. Furthermore, (123)I-MIBG myocardial scintigraphy was highly effective for distinguishing early PD. PMID- 22321866 TI - The development and validation of a quality of life measure for the carers of people with Parkinson's disease (the PDQ-Carer). AB - BACKGROUND: Parkinson's disease (PD) can have substantial effects not only on the quality of life of those diagnosed with the condition but also upon the informal carers who provide support and assistance to them. However, to date no well validated carer specific quality of life measure has been developed for carers of people with PD. OBJECTIVE: This paper documents the development and validation of a PD specific carer quality of life scale. METHODS: In depth interviews were undertaken with carers of people with PD. The interviews were transcribed and analysed thematically to derive a pool of potential items for the questionnaire. A pilot survey was used to refine the initial version of the questionnaire. A developmental survey was undertaken and the results analysed to produce the final 29-item measure. A validation survey was then undertaken to assess the construct validity and reliability of the measure. RESULTS: Survey results suggest a 29 item questionnaire tapping four dimensions of quality of life (Social and Personal Activities, Anxiety and Depression, Self care, and Strain). Internal consistency reliability was found to be high for all domains. Data completeness was high. Construct validity (assessed by correlations with a generic measure of quality of life) confirmed prior hypotheses. CONCLUSION: The 29-item Parkinson Disease Questionnaire for Carers (PDQ-Carer) is a short, meaningful quality of life instrument, which taps areas of specific salience and concern to PD carers. PMID- 22321867 TI - Evidence of a novel galectin-9-binding membrane glycoprotein ligand on T helper cells. PMID- 22321868 TI - Pathogenesis of idiopathic scoliosis: a review. AB - Idiopathic scoliosis is a three-dimensional deformation of the spine. As its name suggests, its pathogenesis remains poorly understood. Enhanced comprehension of its pathogenesis would be likely to improve current therapeutic results. While the hereditary and genetic origin of scoliosis appears unassailable and several chromosomes are known to be involved in transmission, the role assumed by each individual chromosome remains uncertain, and the mechanisms leading to the expression of scoliosis have yet to be determined. Even though a large number of pathogenetic hypotheses have been put forward and numerous studies carried out, none of these hypotheses have won unanimous approval, and the controversy remains persistent. OBJECTIVE: The objective of this paper is to identify the existing hypotheses and to group them within large-scale etiological categories. METHODS: We examined the Pubmed and Goggle databases using as keywords "idiopathic scoliosis" and "pathogenesis". The search was limited to articles in English and French. RESULTS: The vicious cycle hypothesis is markedly preponderant. However, no existing pathogenetic model adequately accounts for the formation of scolioses. CONCLUSION: We are proposing four main pathogenetic mechanisms: asymmetric bone growth dysregulation, susceptibility of bones to deformation, abnormal passive spinal system maintenance and disturbed active spinal system maintenance. PMID- 22321869 TI - Perianal fibroadenoma. PMID- 22321870 TI - Intakes and adequacy of potentially important nutrients for cognitive development among 5-year-old children in the Seychelles Child Development and Nutrition Study. AB - OBJECTIVE: To assess the nutritional adequacy of Seychellois children in relation to nutrients reported to be important for cognitive development. DESIGN: Dietary intakes were assessed by 4 d weighed food diaries and analysed using dietary analysis software (WISP version 3.0; Tinuviel Software, UK). Individual nutrient intakes were adjusted to usual intakes and, in order to investigate adequacy, were compared with the UK Estimated Average Requirements for children aged 4-6 years. SETTING: Children 5 years old were followed up as part of the Seychelles Child Development Nutrition Study (SCDNS), located in the high-fish-consuming population of Mahe, Republic of Seychelles. SUBJECTS: Analysis was carried out on a sample of 229 children (118 boys, 111 girls). RESULTS: Children consumed a diet of which fortified cereal and milk products contributed the most to nutrient intakes. The majority (>=80 %) of children met requirements for several nutrients important for child development including Fe, folate and Se. Adjusted dietary intakes of Cu, Zn, iodine, niacin and vitamin A were below the Estimated Average Requirement or Recommended Nutrient Intake. Mean adjusted energy intakes (boys 4769 kJ/d (1139.84 kcal/d), girls 4759 kJ/d (1137.43 kcal/d)) were lower than the estimated energy requirement (boys 5104 kJ/d (1220 kcal/d), girls 5042 kJ/d (1205 kcal/d)) for 88 % of boys and 86 % of girls. CONCLUSIONS: Nutrition was adequate for most children within the SCDNS cohort. Low intakes of some nutrients (including Zn, niacin and vitamin A) could reflect nutritional database inaccuracies, but may require further investigation. The study provides valuable information on the adequacy of intakes of nutrients which could affect the growth and development of Seychellois children. PMID- 22321871 TI - A comparison of two distinct murine macrophage gene expression profiles in response to Leishmania amazonensis infection. AB - BACKGROUND: The experimental murine model of leishmaniasis has been widely used to characterize the immune response against Leishmania. CBA mice develop severe lesions, while C57BL/6 present small chronic lesions under L. amazonensis infection. Employing a transcriptomic approach combined with biological network analysis, the gene expression profiles of C57BL/6 and CBA macrophages, before and after L. amazonensis infection in vitro, were compared. These strains were selected due to their different degrees of susceptibility to this parasite. RESULTS: The genes expressed by C57BL/6 and CBA macrophages, before and after infection, differ greatly, both with respect to absolute number as well as cell function. Uninfected C57BL/6 macrophages express genes involved in the deactivation pathway of macrophages at lower levels, while genes related to the activation of the host immune inflammatory response, including apoptosis and phagocytosis, have elevated expression levels. Several genes that participate in the apoptosis process were also observed to be up-regulated in C57BL/6 macrophages infected with L. amazonensis, which is very likely related to the capacity of these cells to control parasite infection. By contrast, genes involved in lipid metabolism were found to be up-regulated in CBA macrophages in response to infection, which supports the notion that L. amazonensis probably modulates parasitophorous vacuoles in order to survive and multiply in host cells. CONCLUSION: The transcriptomic profiles of C57BL/6 macrophages, before and after infection, were shown to be involved in the macrophage pathway of activation, which may aid in the control of L. amazonensis infection, in contrast to the profiles of CBA cells. PMID- 22321872 TI - Fate of individuals with ischemic amputations in the REACH Registry: three-year cardiovascular and limb-related outcomes. AB - OBJECTIVE: To evaluate systemic and limb ischemic event rates of PAD patients with prior leg amputation and determine predictors of adverse outcomes. METHODS: The REduction of Atherothrombosis for Continued Health (REACH) Registry provided a prospective multinational cohort of 7996 outpatients with PAD enrolled from primary medical clinics in 44 countries in 2003-2004. 1160 patients (14.5%) had a prior leg amputation at any level. Systemic (myocardial infarction [MI], stroke, cardiovascular death) and limb (angioplasty, surgery, amputation) ischemic event rates were determined in a 3-year follow-up. RESULTS: PAD patients with leg amputations on entry had a 5-fold higher rate of a subsequent amputation (12.4% vs. 2.4%, P<.001), lower rate of peripheral angioplasty (8.3% vs. 10.7%, P = .005), and similar rates of surgical revascularization procedures compared with PAD patients without amputation. A nearly 2-fold increase in rates of cardiovascular death (14.5% vs. 7.7%, P<.001) and all-cause mortality (21.8% vs. 12.6%, P<.001) and an increase in the composite outcome of MI, stroke, cardiovascular death, or hospitalization (48.7% vs. 40.0%, P<.001) were noted. Recent (<= 1 year) amputation was associated with higher rates of worsening PAD, subsequent lower extremity surgical revascularization procedures, re-amputation, non-fatal MI, and the composite outcome, including hospitalization. Adverse systemic and limb ischemic outcomes were similar regardless of amputation level. CONCLUSIONS: Individuals with a history of leg amputations have markedly elevated rates of systemic and limb-related outcomes. PAD patients with recent ischemic amputation have the highest risk of adverse events. A history of "minor" ischemic amputation may confer an identical systemic risk as "major" leg amputation. PMID- 22321873 TI - Maximum carotid intima-media thickness improves the prediction ability of coronary artery stenosis in type 2 diabetic patients without history of coronary artery disease. AB - OBJECTIVE: Carotid intima-media thickness (CIMT), a marker of early atherosclerosis and vascular remodelling, is one of the independent predictors of coronary artery disease (CAD). However, it is unknown whether ultrasonic assessment of carotid atherosclerosis, including CIMT, improves the prediction ability for CAD over and above conventional coronary risk factors in the diabetic patients. METHODS: Ultrasonic scanning of the common carotid artery (CCA), the carotid bulb (Bul), and the internal carotid artery (ICA) was performed. The site with the greatest IMT, including plaque lesions, was sought along the arterial walls and max-IMT (the greatest IMT in the observation-possible areas of the CCA, Bul and ICA) was measured. The association of max-IMT with coronary artery stenosis assessed by coronary computed tomography angiography and the incremental effect of adding max-IMT to the conventional risk factors for predicting coronary artery stenosis were evaluated in 241 asymptomatic type 2 diabetic patients. RESULTS: Multiple logistic regression analyses showed that max-IMT was significantly associated with coronary artery stenosis even after adjustment for conventional risk factors. ROC curve analysis revealed that the AUC significantly increased after addition of max-IMT to conventional coronary risk factors [from 0.64 (95% CI; 0.57-0.71) to 0.74 (95% CI; 0.67-0.80), p = 0.020]. The addition of max-IMT to conventional coronary risk factors increased the AUC in obese patients (from 0.58 to 0.76, p = 0.012) but not in non-obese patients (from 0.68 to 0.72, NS). CONCLUSIONS: In type 2 diabetic patients without apparent cardiovascular disease, the addition of max-IMT to conventional risk factors substantially improves the risk stratification for CAD. PMID- 22321874 TI - Normalization of visceral adiposity is required to normalize plasma apolipoprotein B levels in response to a healthy eating/physical activity lifestyle modification program in viscerally obese men. AB - OBJECTIVE: Little is known about how visceral adipose tissue (VAT) influences circulating apolipoprotein B (apoB) levels, which reflect atherogenic risk. We have examined the effects of a 1-year lifestyle modification program on plasma apoB levels in viscerally obese men and compared post-intervention levels to those of a reference group of lean healthy men. METHODS: Fasting plasma apoB levels were measured in 107 non-diabetic, viscerally obese men, before and after a 1-year lifestyle intervention program aiming at improving nutritional and physical activity/exercise habits. RESULTS: After the intervention, subjects significantly decreased their volume of VAT (Delta = -26 +/- 18%, p < 0.0001) measured by computed tomography and significantly, but modestly reduced their fasting apoB levels (Delta = -3 +/- 14%, p = 0.04). When compared to the reference group, men in the intervention group still had higher apoB levels suggesting that they did not "normalize" their apoB concentrations to the level of the healthy non-obese reference men. To further explore the relationship between VAT and apoB, men in the intervention group were stratified according to quartiles of VAT achieved after the intervention. Only men of the lowest quartile of VAT (corresponding to 844 +/- 42 cm(3), similar to the value of the reference group; 809 +/- 52 cm(3) of VAT) showed plasma apoB levels which were similar to those of the reference group (0.98 +/- 0.21 vs. 0.99 +/- 0.24 g/L, NS, for lowest VAT quartile and reference group, respectively). CONCLUSION: These results suggest that, in order to "normalize" apoB levels in response to a lifestyle modification program, viscerally obese dyslipidemic men need to achieve levels of VAT similar to healthy non-obese men. PMID- 22321875 TI - Generalized anxiety modulates frontal and limbic activation in major depression. AB - BACKGROUND: Anxiety is relatively common in depression and capable of modifying the severity and course of depression. Yet our understanding of how anxiety modulates frontal and limbic activation in depression is limited. METHODS: We used functional magnetic resonance imaging and two emotional information processing tasks to examine frontal and limbic activation in ten patients with major depression and comorbid with preceding generalized anxiety (MDD/GAD) and ten non-depressed controls. RESULTS: Consistent with prior studies on depression, MDD/GAD patients showed hypoactivation in medial and middle frontal regions, as well as in the anterior cingulate, cingulate and insula. However, heightened anxiety in MDD/GAD patients was associated with increased activation in middle frontal regions and the insula and the effects varied with the type of emotional information presented. CONCLUSIONS: Our findings highlight frontal and limbic hypoactivation in patients with depression and comorbid anxiety and indicate that anxiety level may modulate frontal and limbic activation depending upon the emotional context. One implication of this finding is that divergent findings reported in the imaging literature on depression could reflect modulation of activation by anxiety level in response to different types of emotional information. PMID- 22321876 TI - [A thorough knowledge of airway stents is essential and their indications should be strictly gauged]. PMID- 22321877 TI - [Correlation factor analysis of pan-drug resistant Acinetobacter baumannii strains in acquired infections]. AB - OBJECTIVE: To explore the clinical factors, drug resistance and molecular epidemiology homologous characteristics of pan-drug resistant Acinetobacter baumannii (PDRAB) in acquired infections and analyze the correlation factor between epidemic characteristics and acquired infections. METHODS: A total of 60 PDRAB strains from nine acquired infections and related clinic data were collected from January 2009 to January 2011. The drug-resistant phenotype was tested by disk diffusion methods. The isolate identification and homology were studied by automation repetitive-element sequence-based (REP)-PCR typing platform from genes and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-TOF MS) from proteins. RESULTS: All strains were resistant to 12 antibiotics except 2 strains to imipenem and meropenem. The strains in this study were divided into 12 types (A-L) by REP-PCR. And 60 strains were also clustered to a-e types by MALDI-TOF-TOF MS. Compared with MALDI-TOF-TOF MS, REP-PCR tended to be more accurate. Breathing machine carriage and cross transmission were the main reasons for a major epidemic outbreak at department of pulmonary medicine from July 2009 to October 2009. Hand transmission of medical care personnel was a key factor for SICU 2010 January to February. The contamination and transmission to environment of PDRAB in nasal pharynx or respiratory tract by superspreader were the main reasons for the other 7 epidemic outbreaks. Department of emergency medicine was the source of acquired infections. CONCLUSION: The key control measures of acquired infections are early identification and isolation of spreader, environment and instrument disinfection, hand washing and rational uses of antibiotics. MALDI-TOF-TOF MS will become a preferred tool of identification and classification of microorganisms because of its simple operation, affordable price and handling rapidity. PMID- 22321878 TI - [Correlation between orthostatic hypotension and cardiovascular risks in elderly population]. AB - OBJECTIVE: To investigate the correlation between orthostatic hypotension and cardiovascular risks and hospitalization rate in the elders. METHODS: A total of 1174 people over 65 years old underwent health screening physical examination through a self-made questionnaire at our hospital. Their clinical data were collected. The orthostatic blood pressure and heart rate were measured in supine position after resting for over 5 minutes and at 0 and 2 min after standing. Orthostatic hypotension was defined as 20 mm Hg or greater decrease in SBP or/and 10 mm Hg or greater decrease in DBP after standing. All cases were followed up by telephone or hospitalization medical records for a mean period of 315.8 days. The primary endpoint was the occurrence of such cardiovascular or cerebrovascular events as angina, fatal or nonfatal myocardial infarction (MI), congestive heart failure, sudden cardiac death, ischemic and hemorrhagic stroke. RESULTS: The prevalence of OH was 25.6% in this cohort. Significant differences could be found in the rate of all-cause and cardiovascular-related hospitalization between OH positive and OH negative (45.1% vs 32.5%; 19.1% vs 7.4%); the rates of angina and myocardial infarction in the OH positive group were significantly higher than those in the OH negative group (7.5% vs 3.7%: 4.8% vs 0.5%, P < 0.05); after adjusting for age, supine blood pressure, heart rate and cerebrovascular history by logistic regression, statistical differences could also be observed between OH and angina [P = 0.011, HR (hazard ratio): 2.122, 95%CI (confidence interval): 1.184-3.802 and MI (P < 0.001, HR: 8.995, 95%CI: 2.909 - 27.819)]. CONCLUSION: Orthostatic hypotension may increase the rates of all-cause and cardiovasular related hospitalization. And it is a robust predictor of angina and myocardial infarction in the elders. PMID- 22321879 TI - [Pathogenic effects of level of nitric oxide, hyponatremia and heart function on hepatorenal syndrome]. AB - OBJECTIVE: To analyze the changes of liver function, renal function, electrolytes, heart function and serum nitric oxide (NO) in chronic severe hepatitis patients with hepatorenal syndrome (HRS) by plasma exchange (PE), study the relationship of NO, hyponatremia, heart function with HRS. METHODS: A total of 20 chronic severe hepatitis patients with HRS were recruited. All were treated thrice by PE. The parameters of blood pressure, heart rate, 24 h urinary volume, liver function indicators, renal function indicators, NO, cardiac troponin T (cTnT), brain natriuretic peptide (BNP), aldosterone, interleukin-6, tumor necrosis factor-alpha and plasma ammonia were measured before PE, during PE and after PE. Their differences were compared before, during and after PE. RESULTS: The NO level of HRS before PE was (113 +/- 26) umol/L, the level of Day 1 after PE (78 +/- 24) umol/L and the level of Day 3 after PE was (85 +/- 29) umol/L. All NO levels were lower than that before PE (all P < 0.05). Creatine level of HRS before PE was (191 +/- 43) umol/L and the level of Day 1 after PE (142 +/- 42) umol/L. All levels were lower than that before PE (all P < 0.05). The level of Day 3 after PE was 221 +/- 105 umol/L and it was higher than that before PE (P < 0.05). At pre-, during- and post-PE, the level of sodium was low than normal (normal range: 135 - 145 mmol/L), the level of aldosterone higher than normal (normal range: 10 - 27 ng/L), the level of cTnT higher than normal (normal range: < 14 ng/L) and the level of BNP higher than normal (normal range: < 366 ng/L). The levels of model for end-stage liver disease (MELD) score, bilirubin, urea, cysteine proteinase inhibitor C and ammonia decreased during PE, but increased post-PE. Systolic pressure and 24 h urinary volume decreased gradually. In this study, 8 patients died and 12 were discharged from hospital. CONCLUSION: Serum nitric oxide is not the sole occurring factor for hepatorenal syndrome. Hyponatremia and impaired heart function may be the key factors for hepatorenal syndrome. PMID- 22321880 TI - [Combined and sequential therapy for Kasabach-Merritt syndrome]. AB - OBJECTIVE: To review and summarize the clinical characteristics and therapeutic approaches of Kasabach-Merritt syndrome (KMS). METHODS: The combined and sequential therapy was used to for 51 KMS infants between 2005 and 2009. And all cases were retrospectively analyzed. There were 27 males and 24 females with a median age of 1.8 months (range: 2 days to 2.5 years). Among them, lesions were located in maxillofacial (n = 20), truck (n = 4), upper extremities (n = 11) and lower extremities (n = 16). RESULTS: Among them, 47 of 51 patients were cured, 3 cases were effectively treated and only 1 patient died of multiple organ failure post-operation. Of the 51 cases, emergency surgery was given in 3 cases while other 48 cases were initially treated with methylprednisolone. The responses were varied: excellent and rapid improvement (n = 12); moderate response (n = 15) and total failure (n = 21). Immunoglobulin was used a second-line therapy for those (n = 21) unresponsive to steroid, with sensitive response (n = 5), effective response (n = 7) and invalid response (n = 9) respectively. And adjunct carbonyldiamide therapy was combined. Conservative treatment was tried in 14 patients. Then 11 curative cases and 3 effective cases were observed. The thrombocyte count in 4 cases returned to normal within 4 - 7 days, 5 cases within 8 - 14 days, and 2 cases within 15 - 28 days. In the remaining 3 cases, it normalized more than 28 days. The hemangiomas in 6 cases disappeared completely in 6 - 12 months and 8 cases disappeared in 13 - 24 months. 19 patients were treated with the ligation of external carotid artery, the insertion of a tube inside the lesion and the injections of carbonyldiamide and methylprednisolone. The platelet counts of 13 cases increased to normal in 4 - 7 days of the treatment, and 6 cases in 8 - 14 days. The tumors of 12 cases disappeared within 6 - 12 months, and 7 cases within 13 - 24 months. Combined surgical resection including emergency operation (n = 3) and selective operation (n = 15) was performed in 18 patients. And all cases except for one were cured. The platelet counts of that the hemangiomas of 10 cases were excised surgically completely increased rapidly and reached the normal range in post-operative 1 - 3 days. The counts of 8 cases after subtotal resection increased to normal within 8-14 days. CONCLUSION: A stepwise multimodal approach is recommended for the treatment of KMS. With a higher curative rate, it has minimal side effects. PMID- 22321881 TI - [Protein expression and significance of survivin and NF-kappaB in hepatocellular carcinoma]. AB - OBJECTIVE: To detect the protein expressions of survivin and NF (nuclear factor) kappaB and investigate their roles in the pathogenesis of hepatocellular carcinoma. METHODS: A total of 206 cases were diagnosed as hepatocellular carcinoma, and immunohistochemical technique was used to detect the protein expressions of survivin and NF-kappaB in hepatocellular carcinoma samples and normal liver tissue specimens. Statistical analysis was performed to analyze the relationship of protein expressions of survivin and NF-kappaB and clinico pathological parameters and prognosis. RESULTS: The expression of survivin was predominant in cytoplasm while that of NF-kappaB was in nucleolus. The positive rate of survivin protein was 78.2% in hepatocellular carcinoma and that of NF kappaB was 81.1%. The positive rate of survivin and NF-kappaB was higher in hepatocellular carcinoma than that in benign hepatic tissue (11.7% and 15.5%). Significant differences existed in the expressions of survivin and NF-kappaB between hepatocellular carcinoma and normal hepatic tissue (P < 0.01). The expression of survivin was related to amicula invasion, portal vein tumor thrombus, lymph node metastasis and clinical stage in hepatocellular carcinoma (P < 0.01). The expression of NF-kappaB was also related to portal vein tumor thrombus, lymph node metastasis and clinical stage in hepatocellular carcinoma (P < 0.05). There was an obviously positive correlation between the expressions of survivin and NF-kappaB in hepatocellular carcinoma (r = 0.52, P < 0.01). Survival rate of patients for 1, 3 year of positive expression of survivin and NF-kappaB in hepatocellular carcinoma was 70.3% and 30.4%, respectively. And it was obviously lower than that of those of negative expression (88.5% and 61.5%). There was significant difference in the expressions of survivin and NF-kappaB between positive and negative subjects in 1, 3 year (P < 0.05). CONCLUSION: Protein expressions of survivin and NF-kappaB are higher in hepatocellular carcinoma. And they play mutually promoting roles in the development of hepatocellular carcinoma. Thus, an important prognostic indicator may be adopted. PMID- 22321882 TI - [Expression of liver-intestine cadherin and its significance in hepatocellular carcinoma]. AB - OBJECTIVE: To explore the expression and clinical significance of LI (liver intestine)-cadherin mRNA and protein expression level in hepatocellular carcinoma. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical techniques were used to detect the expression of the LI cadherin mRNA and protein in 56 cases of hepatocellular carcinoma, 44 cases of corresponding paracancerous tissues and 9 cases of normal liver tissues. The relationships with its clinicopathological characteristics were analyzed. RESULTS: The mRNA of LI-cadherin was expressed in 56 cases of hepatocellular carcinoma tissues and 44 cases of corresponding paracancerous tissues. But its expression was not detected in normal tissues. Semiquantitative analysis showed that the mRNA expression level of LI-caherin was greater in hepatocellular carcinoma tissues than that in corresponding paracancerous tissues (0.653 +/- 0.147 vs 0.534 +/- 0.138). The differences were statistically significant (P < 0.01). The positive rates of LI-cadherin protein were 64.29% (36/56) in hepatocellular carcinoma tissues, 22.73% (10/44) in paracancerous tissues and 0% (0/9) in normal tissues. CONCLUSION: The expression of LI-cadherin is up regulated significantly in HCC. The over-expression of LI-cadherin protein is correlated with the lymph node metastasis and tumor thrombi in portal vein. It indicates that LI-cadherin may play an important role in the progression and metastasis of HCC. PMID- 22321883 TI - [Radiofrequency ablation-assisted laparoscopic partial nephrectomy without renal hilar vessel clamping: a report of 14 cases]. AB - OBJECTIVE: To evaluate the clinical feasibility of radiofrequency ablation assisted laparoscopic partial nephrectomy (RF-LCPN) without renal hilar vessel clamping. METHODS: From January 2009 to June 2010, 14 cases with renal tumors were treated with RF-LCPN. The mean tumor size was 3.1 cm (range: 2.2 - 4.0 cm). All cases were staged at T(1a)N(0)M(0). The preoperative serum creatinine (SCr) was (87 +/- 36) umol/L and glomerular filtration rate (GFR) (45 +/- 11) ml/min. RESULTS: RF-LCPN was technically successful in all patients (14 tumors). The mean operative time was (152 +/- 46) min and the mean blood loss (89 +/- 52) ml. All tumor margins were negative. One patient with a brief period of urine leakage from lower pole calix was managed successfully by ureteral stenting and Foley catheter drainage of bladder. The postoperative hospital stay was (5 +/- 2) days. The postoperative SCr was (90 +/- 38) umol/L and GFR (41 +/- 12) ml/min. There was no statistic post-operative change of SCr and GFR (P > 0.05). All patients completed a minimum follow-up of 6 months (mean: 17 months, range: 6 - 25 months). No evidence of local or port-site recurrence or metastasis was found. CONCLUSION: As an accurate and effective intervention with a relatively low incidence of complications, RF-LCPN may eliminate renal warm ischemia. But its long-term efficacy remains to be further studied. PMID- 22321884 TI - [Single trocar laparoscopic surgery: a report of 45 cases]. AB - OBJECTIVE: To report the initial urological applications of single trocar laparoscopic surgery. METHODS: From April to December 2010, a total of 45 urologic patients underwent single trocar laparoscopic surgery. The procedures included high ligations of spermatics vessels (n = 17), unroofing of renal cysts (n = 24) and ureterolithotomy (n = 4). Transperitoneal approach: A 15 mm incision was made in umbilicus and CO(2) pneumoperitoneum created. A 10-mm trocar was inserted into enterocoelia. After the installation of single punch laparoscope (STROZ), the operating instruments were guided through integrated working channel to complete operative procedures. Retroperitoneal approach: A 15 mm incision was made above the diseased-side crista iliaca for around 4 cm. Retroperitoneal cavity was prepared for retroperitoneoscopy with the IUPU (Institute of Urology, Peking University) technique. In the same way, a 10-mm trocar was inserted. And the single punch laparoscope was installed to complete operative procedures. RESULTS: The procedures were successful in 41 cases. But the others (renal cysts, n = 2; ureteral calculus, n = 2) were successfully managed by adding a 5 mm trocar. Operation time: transperitoneal approach, 23 - 70 min; retroperitoneal approach, 45 - 175 min. The intra-operative volume of blood loss was minimal. And the hospital stay was 1 - 5 days. No significant postoperative complication occurred. CONCLUSION: For some relatively simple procedures, a new and more minimally invasive approach of single trocar laparoscopic surgery may be attempted. PMID- 22321885 TI - [Efficacy and safety of palonosetron versus tropisetron in the prevention of highly emetogenic chemotherapy-induced acute and delayed vomiting in Chinese cancer patients]. AB - OBJECTIVE: To explore the efficacy and safety of palonosetron in the prevention of acute and delayed chemotherapy-induced nausea and vomiting after moderate to severe emetogenic chemotherapy. METHODS: From November 2008 to November 2009, a multicenter, randomized, double-blind and self-crossover phase II clinical trial with a total planned enrollment of 160 patients was carried out to compare palonosetron (drug A) with tropisetron (drug B). The subjects were randomized divided into groups AB and BA. The dosing sequence in the group AB was drug A the first cycle and drug B the second cycle while the BA group was administered reversely. The efficacy was evaluated within a period of 5 days after cisplatin or adriamycin-based regimen chemotherapy. Adverse effects were assessed by CTCAE 3.0. RESULTS: Among 155 enrolled cases, 132 cases were assessable for efficacy. The complete control rate of acute chemotherapy-induced nausea and vomiting was 54.55% vs 51.52% for drug A vs drug B (P > 0.05), but that of delayed reaction was 53.03% vs 38.64% respectively. There were significant differences (P = 0.01). Meanwhile, the rate of adverse effects was 4.90% for investigational agent without severe adverse events. The main adverse reactions were headache and dizziness. CONCLUSION: With a high safety profile, palonosetron is an effective agent for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. PMID- 22321886 TI - [Clinical efficacies of ABO-incompatible adult liver transplantation]. AB - OBJECTIVE: To evaluate the efficacy and safety of ABO-incompatible liver transplantation in adult patients with fulminant hepatitis B. METHODS: The clinical data of 97 cases of adult liver transplantation for fulminant hepatitis B were retrospectively analyzed. The patients were grouped as ABO-identical (ABO Id, n = 58), ABO-compatible (ABO-C, n = 19) and ABO-incompatible (ABO-In, n = 20). The rates of rejection, infection, biliary tract complications, vascular complications, and patient and graft survivals were compared among 3 groups. RESULTS: The 3-month, 1-year and 3-year graft survival rates were 87.9%/77.6%/65.3% in ABO-Id group, 84.2%/73.7%/66.5% in ABO-C group and 50.0%/35.0%/33.3% in ABO-In group respectively. There were significant differences between ABO-Id and ABO-In (P < 0.05). The incidences of rejection, infection, vascular complications and biliary tract complications were 8.6%, 20.7%, 3.4% and 6.9% in ABO-Id group, 35%, 60%, 20% and 30% in ABO-In group (P < 0.05) and 10.5%, 26.3%, 5.3% and 10.5% respectively in ABO-C group (P > 0.05). CONCLUSION: ABO-C liver transplantation is an important therapeutic option in adult patients with acute liver failure awaiting an emergency procedure. ABO-In transplantation can be used only for life-rescuing in patients with fulminant hepatitis since it is associated with a higher risk of rejection, infection, vascular thrombosis, ischemic bile duct complications and poor patient and graft survival. PMID- 22321887 TI - [Diagnosis and treatment for adrenal ganglioneuroma]. AB - OBJECTIVE: To evaluate the clinical characteristics,diagnosis and treatment for adrenal ganglioneuroma. METHODS: Thirty cases of adrenal ganglioneuroma at our hospital from 1999 to 2010 were reviewed. Their clinical, radiological, laboratory and pathologic findings as well as follow-up data were analyzed retrospectively. RESULTS: There were 12 males and 18 females with an age range of 7 - 63 (23.8 +/- 11.4) years old. Tumor size ranged from 2.5 cm to 15 cm. Fourteen (46.7%) cases were found incidentally without any overt symptom. And the presenting symptoms and signs of the others were paroxysmal headache and palpitation (n = 7, 23.3%), hypertension (n = 5, 16.7%) and flank or abdominal pain (n = 4, 13.3%). All cases underwent open or laproscopic operations and their diagnosis of adrenal ganglioneuroma was confirmed pathologically. An oval or crescentic well-defined mass, low or intermediate attenuation on CT (computed tomography) scan was found in most cases. Tumors partially or completely surrounded major blood vessels in 9 cases while 7 cases had discrete punctuate calcification. The 24-hours urinary catecholamine and urinary free cortisol output were within a normal range. Seventeen cases underwent a (99)Tc-octreotide scan and negative results were found in 15 cases. Seven cases had a (131)I Metaiodobenzylguanidine ((131)I-MIBG) scan and all results were negative. Twenty one cases were diagnosed empirically as adrenal ganglioneuroma. One case was found pre-operatively with multiple bone metastases. Among all cases, either open operation (n = 11) or retroperitoneal laparoscopic excision (n = 19) was performed successfully. All recovered smoothly. One patient with pre-operative bone metastasis developed progression. No recurrence was detected after a follow up period of 1 - 11 years. CONCLUSION: Mostly benign in nature, adrenal ganglioneuromas is often found incidentally without specific clinic symptoms. A relatively accurate preoperative diagnosis can be made on the basis of a detailed history and the relevant imaging and laboratory results. Surgical resection of tumor is a preferred choice with a fairy good prognosis. PMID- 22321888 TI - [RAD001 reverses radio-resistance and exerts synergistic tumor inhibition with 5 fluorouracil]. AB - OBJECTIVE: To explore the in vitro synergistic anti-tumor efficacy of mammalian target of rampamycin (mTOR) inhibitor (RAD001) and 5-fluorouracil (5-FU) for radio-resistant tumors. METHODS: Radio-resistant cells of human pancreatic cancer cell and human colon cancer cell were established. The expression profiles of VEGF (vascular endothelial growth factor) and TP (thymidine phosphorylase) were compared between parental and radio-resistant tumor cells. The tumor proliferation was analyzed after 5-FU alone or in combination with a mTOR inhibitor. RESULTS: After several cycles of radiation induction (3 Gy), the radio resistant cells of human pancreatic cancer (AsPCres) and colon cancer (HT29res) were established. There was a higher expression of VEGF in radio-resistant tumor cells than their parental cells. They were 1215 +/- 67 pg/ml in AsPCres and 689 +/- 25 pg/ml in HT29res respectively (P < 0.01). The up-regulation of TP was observed in both AsPC-res and HT29-res. The combined therapy of 5-FU plus a mTOR inhibitor might exert synergistic tumor inhibition. CONCLUSION: RAD001 decreases the radiation-induced expression of VEGF in tumor. And the post-radiation up regulation of TP promotes the efficacy of 5-FU. The combined therapy of RAD001 and 5-FU may inhibit synergistically the growth of radio-resistant tumors. PMID- 22321889 TI - [Angiogenesis of full-thickness burn wounds repaired with collagen-sulfonated carboxymethyl chitosan porous scaffold encoding vascular endothelial growth factor DNA plasmids]. AB - OBJECTIVE: To investigate the effects of vascular endothelial growth factor (VEGF) DNA plasmids, encoded in collagen-sulfonated carboxymethyl chitosan porous scaffold, on the angiogenesis in full-thickness burn wounds. METHODS: Wounds and pathological changes were observed at Week 1, 2, 3 and 4 after pure collagen sulfonated carboxymethyl chitosan porous scaffold (group A) and collagen sulfonated carboxymethyl chitosan porous scaffold encoding VEGF DNA plasmids (group B) were transplanted onto eachar-removed wounds of full-thickness burn in 6 Bama miniature pigs respectively. Wound healing was observed by pathologic slides after epidermal grafting for 2 weeks (at Week 4) onto the surface of different dermal scaffolds transplanted on wounds for 2 weeks. At the same time, new-forming vessels expressing CD31 and mature vessels expressing alpha-SMA (alpha-smooth muscle actin) and the expression of VEGF in wounds at Week 1, 2, 3 and 4 were detected in situ by immunohistochemical staining. The burn wounds without any transplanted scaffold (group C) were studied as the controls. RESULTS: Wounds with various scaffolds were different from those without any scaffold. Angiogenesis of the group B was better than that of the group A. Neo forming micro-vessels expressing CD31 in the wounds of group A or B at Week 1, 2, 3 and 4 were as follows: 18.7 +/- 3.1, 25.7 +/- 2.3, 36.8 +/- 2.5 & 26.2 +/- 2.9; 24.5 +/- 3.8, 32.3 +/- 2.8, 39.2 +/- 2.2 & 27.3 +/- 3.0. Mature vessels expressing alpha-SMA: 11.7 +/- 1.9, 20.5 +/- 1.9, 35.0 +/- 4.5 & 24.0 +/- 2.8; 20.2 +/- 3.1, 33.5 +/- 3.7, 38.2 +/- 4.5 & 26.5 +/- 2.3. The expressions of VEGF: 48.7 +/- 7.9, 141.7 +/- 9.1, 201.5 +/- 8.6 & 107.0 +/- 8.2; 97.3 +/- 7.9, 172.3 +/- 8.1, 208.7 +/- 8.3 & 114.0 +/- 5.8. Expressing intensity of CD31, alpha-SMA and VEGF in the wounds of group C at Week 1, 2, 3 & 4: 6.0 +/- 2.0, 9.8 +/- 3.4, 19.3 +/- 2.5 & 18.7 +/- 2.2; 3.7 +/- 2.0, 8.7 +/- 1.8, 13.0 +/- 2.5 & 14.0 +/- 2.8; 3.5 +/- 2.3, 10.3 +/- 3.5, 23.0 +/- 5.6 & 21.5 +/- 5.1. There were significant statistical differences among three groups. CONCLUSION: Artificial dermal scaffold encoding exogenous pDNA-VEGF can promote a quicker angiogenesis through a high expression of VEGF. Thus a full-thickness burn wound may be better repaired. PMID- 22321890 TI - [Expression of aquaporin-4 during brain edema in rats with thioacetamide-induced acute encephalopathy]. AB - OBJECTIVE: To investigate the expression of aquaporin-4 (AQP4) during brain edema in rats with thioacetamide-induced acute liver failure and encephalopathy. METHODS: The rat model of acute hepatic failure and encephalopathy was induced by intraperitoneal injection of thioacetamide (TAA) at a 24-hour interval for 2 consecutive days. Thirty-two SD rats were randomly divided into the model group (n = 24) and the control group (normal saline, n = 8). And then the model group was further divided into 3 subgroups by the timepoint of decapitation: 24 h (n = 8), 48 h (n = 8) and 60 h (n = 8). Then we observed their clinical symptoms and stages of HE, indices of liver function and ammonia, liver histology and brain water content. The expression of AQP4 protein in brain tissues was measured with Western blot and the expression of AQP4mRNA with RT-PCR (reverse transcription polymerase chain reaction). RESULTS: Typical clinical manifestations of hepatic encephalopathy occurred in all TAA-administrated rats. The model rats showed the higher indices of ALT (alanine aminotransferase), AST (aspartate aminotransferase), TBIL (total bilirubin) and ammonia than the control rats (P < 0.05). The brain water content was significantly elevated in TAA-administrated rats compared with the control (P < 0.05). The expressions of AQP4 protein and mRNA in brain tissues significantly increased in TAA-administrated rats (P < 0.05). In addition, the expressions of AQP4 protein and mRNA were positively correlated with brain water content (r = 0.536, P < 0.01; r = 0.566, P = 0.01). CONCLUSIONS: The high expression of AQP4 in rats with TAA-induced acute liver failure and encephalopathy plays a significant role during brain edema. AQP4 is one of the molecular mechanisms for the occurrence of brain edema in hepatic encephalopathy. PMID- 22321891 TI - [Effects of osteopontin on gap junctional intercellular communication in colon cancer cell lines]. AB - OBJECTIVE: Liver metastasis is a major cause of mortality in patients with colorectal cancer. However, the mechanisms underlying this process remain largely unknown. Osteopontin (OPN) is a secreted phosphorylated glycoprotein known to be involved in tumor migration and metastasis. Gap junction intercellular communication (GJIC) is a pathway of direct cell to cell communication. This study analyzed gap junctional intercellular communication (GJIC) changes in colon cancer SW-480 cell lines after osteopontin had been transfected in. METHODS: Transfect sense-osteopontin eukaryotic expression plasmids into SW-480 cell lines and detect the GJIC changes in two different cell lines by flurescence redistribution after photobleaching (FRAP). RESULTS: Compared with control, signal exchange is impaired and GJIC function is inhibited in SW-480-pcDNA3.1(+) OPN cell lines. FRAP after 5 min in SW-480-pcDNA3.1(+)-OPN is 24.65% +/- 4.08%,the control SW-480-pcDNA3.1(+) is 44.74% +/- 6.23%,P < 0.001;FRAP after 10 min in SW-480-pcDNA3.1(+)-OPN is 25.98% +/- 4.48%, while SW-480-pcDNA3.1 is up to 64.92% +/- 5.39%,P < 0.001. CONCLUSION: OPN could inhibit GJIC function of colon cells to accelerate the metastatic process in colorectal cancer. PMID- 22321892 TI - Blind trials of computer-assisted structure elucidation software. AB - BACKGROUND: One of the largest challenges in chemistry today remains that of efficiently mining through vast amounts of data in order to elucidate the chemical structure for an unknown compound. The elucidated candidate compound must be fully consistent with the data and any other competing candidates efficiently eliminated without doubt by using additional data if necessary. It has become increasingly necessary to incorporate an in silico structure generation and verification tool to facilitate this elucidation process. An effective structure elucidation software technology aims to mimic the skills of a human in interpreting the complex nature of spectral data while producing a solution within a reasonable amount of time. This type of software is known as computer-assisted structure elucidation or CASE software. A systematic trial of the ACD/Structure Elucidator CASE software was conducted over an extended period of time by analysing a set of single and double-blind trials submitted by a global audience of scientists. The purpose of the blind trials was to reduce subjective bias. Double-blind trials comprised of data where the candidate compound was unknown to both the submitting scientist and the analyst. The level of expertise of the submitting scientist ranged from novice to expert structure elucidation specialists with experience in pharmaceutical, industrial, government and academic environments. RESULTS: Beginning in 2003, and for the following nine years, the algorithms and software technology contained within ACD/Structure Elucidator have been tested against 112 data sets; many of these were unique challenges. Of these challenges 9% were double-blind trials. The results of eighteen of the single-blind trials were investigated in detail and included problems of a diverse nature with many of the specific challenges associated with algorithmic structure elucidation such as deficiency in protons, structure symmetry, a large number of heteroatoms and poor quality spectral data. CONCLUSION: When applied to a complex set of blind trials, ACD/Structure Elucidator was shown to be a very useful tool in advancing the computer's contribution to elucidating a candidate structure from a set of spectral data (NMR and MS) for an unknown. The synergistic interaction between humans and computers can be highly beneficial in terms of less biased approaches to elucidation as well as dramatic improvements in speed and throughput. In those cases where multiple candidate structures exist, ACD/Structure Elucidator is equipped to validate the correct structure and eliminate inconsistent candidates. Full elucidation can generally be performed in less than two hours; this includes the average spectral data processing time and data input. PMID- 22321893 TI - Evaluation of naturally occurring radioactive materials (NORM) in the South Western oil wells of Iran. AB - An investigation was carried out to find out the concentration of Naturally Occurring Radioactive Materials (NORMs) in an oil production unit, an evaporation pond, and a drilling site in the Khuzestan province, in south west Iran the 4th largest oil producing country in the world. The nuclides (232)Th and (40)K were determined in soil samples and (226)Ra was analyzed in both soil and water. The (232)Th ranged between 8.7 and 403 Bq kg(-1), while the minimum concentration for (40)K was much larger, i.e. 82 Bq kg(-1) and its maximum concentration was 815 Bq kg(-1). Soil samples indicated very low concentrations of (226)Ra, typically between 10.6 and 42.1 Bq kg(-1) with some exceptions of 282, 602, and even 1480 Bq kg(-1). Also, the range for (226)Ra in water was less from 0.1 to a maximum 30.3 Bq L(-1). Results show that on average, NORM concentrations in these areas are lower in comparison with the usual concentration levels in typical oil and gas fields, but despite this fact, necessary measures have to be taken in order to minimize the environmental impact of radioactive materials. PMID- 22321894 TI - Prediction of HIV-1 protease/inhibitor affinity using RosettaLigand. AB - Predicting HIV-1 protease/inhibitor binding affinity as the difference between the free energy of the inhibitor bound and unbound state remains difficult as the unbound state exists as an ensemble of conformations with various degrees of flap opening. We improve computational prediction of protease/inhibitor affinity by invoking the hypothesis that the free energy of the unbound state while difficult to predict is less sensitive to mutation. Thereby the HIV-1 protease/inhibitor binding affinity can be approximated with the free energy of the bound state alone. Bound state free energy can be predicted from comparative models of HIV-1 protease mutant/inhibitor complexes. Absolute binding energies are predicted with R = 0.71 and SE = 5.91 kJ/mol. Changes in binding free energy upon mutation can be predicted with R = 0.85 and SE = 4.49 kJ/mol. Resistance mutations that lower inhibitor binding affinity can thereby be recognized early in HIV-1 protease inhibitor development. PMID- 22321895 TI - Kinetics of thermal de-chlorination of PVC under pyrolytic conditions. AB - Although PVC-containing wastes are an important potential source of energy they are frequently disposed in landfill. In thermal treatment processes such as pyrolysis and gasification, the presence of poly(vinyl chloride) (PVC), a compound with 56.7% of chlorine, may cause problems concerned with environmental protection, as consequence of the formation of hydrochloric acid, chlorine gas and dioxins, as well as corrosion phenomena of the reactor/equipment materials. Thus, a possible solution may involve a previous removal of the chlorine from PVC containing waste through a pyrolysis process at low temperatures before the material being submitted to a subsequent thermal treatment, for energetic valorization. In this work, a kinetic model for the thermal decomposition of PVC has been developed, in view of its de-chlorination. DTA/TGA testing at different temperatures indicated a first order reaction and an activation energy of 133,800J/mol. An almost completed de-chlorination reaction was obtained at 340 degrees C under an inert atmosphere. The resulted material is a C(n)H(n) type polymer with potential to be used in an energy recovery process. Validation test performed at laboratory scale indicate that the temperature of 340 degrees C enables the removal of ~99.9% of the chlorine present in PVC. The chloride can be fixed in the form of an aqueous solution of HCl or calcium chloride, driving to an alternative full process with environmental benefits and reduction of the costs associated to the PCV - containing materials/wastes management. PMID- 22321896 TI - Methodology for quantification of waste generated in Spanish railway construction works. AB - In the last years, the European Union (EU) has been focused on the reduction of construction and demolition (C&D) waste. Specifically, in 2006, Spain generated roughly 47million tons of C&D waste, of which only 13.6% was recycled. This situation has lead to the drawing up of many regulations on C&D waste during the past years forcing EU countries to include new measures for waste prevention and recycling. Among these measures, the mandatory obligation to quantify the C&D waste expected to be originated during a construction project is mandated. However, limited data is available on civil engineering projects. Therefore, the aim of this research study is to improve C&D waste management in railway projects, by developing a model for C&D waste quantification. For this purpose, we develop two equations which estimate in advance the amount, both in weight and volume, of the C&D waste likely to be generated in railway construction projects, including the category of C&D waste generated for the entire project. PMID- 22321897 TI - Separate collection of household food waste for anaerobic degradation - Comparison of different techniques from a systems perspective. AB - Four systems for household food waste collection are compared in relation the environmental impact categories eutrophication potential, acidification potential, global warming potential as well as energy use. Also, a hotspot analysis is performed in order to suggest improvements in each of the compared collection systems. Separate collection of household food waste in paper bags (with and without drying prior to collection) with use of kitchen grinders and with use of vacuum system in kitchen sinks were compared. In all cases, food waste was used for anaerobic digestion with energy and nutrient recovery in all cases. Compared systems all resulted in net avoidance of assessed environmental impact categories; eutrophication potential (-0.1 to -2.4kg NO(3)(-)eq/ton food waste), acidification potential (-0.4 to -1.0kg SO(2)(-)eq/ton food waste), global warming potential (-790 to -960kg CO(2)(-)eq/ton food waste) and primary energy use (-1.7 to -3.6GJ/ton food waste). Collection with vacuum system results in the largest net avoidence of primary energy use, while disposal of food waste in paper bags for decentralized drying before collection result in a larger net avoidence of global warming, eutrophication and acidification. However, both these systems not have been taken into use in large scale systems yet and further investigations are needed in order to confirm the outcomes from the comparison. Ranking of scenarios differ largely if considering only emissions in the foreground system, indicating the importance of taking also downstream emissions into consideration when comparing different collection systems. The hot spot identification shows that losses of organic matter in mechanical pretreatment as well as tank connected food waste disposal systems and energy in drying and vacuum systems reply to the largest impact on the results in each system respectively. PMID- 22321898 TI - [Use of ustekinumab in inflammatory bowel disease: apropos of three cases]. PMID- 22321899 TI - PARP-1 inhibition induces a late increase in the level of reactive oxygen species in cells after ionizing radiation. AB - Poly(ADP-ribose) polymerase 1 (PARP1), an enzyme activated by DNA strand breaks, synthesizes polymers of poly(ADP-ribose) (PAR) that modify chromatin and other proteins and play a role in DNA repair. Inhibition of PARP1 activity is considered a potentially important strategy in clinical practice, especially to sensitize tumor cells to chemo- and radio-therapy. Here we examined the influence of inhibition of PARP1 on formation of reactive oxygen species (ROS) and on DNA repair in cells exposed to ionizing radiation (IR). K562 (human myelogenous leukaemia) cells were grown and exposed to 4 or 12 Gy of ionizing radiation in presence or absence of the PARP inhibitor NU1025 (100 MUM). Intracellular ROS were assayed using the probe 2,7-dichlorofluorescein with detection by flow cytometry and the rejoining of DNA strand breaks were followed by alkaline single cell gel electrophoresis (comet) assays. In untreated cells a significant increase in PAR formation occurred during the first 5 min after IR, followed by a gradual decrease up to 30 min. Addition of a PARP inhibitor arrested the production of PAR almost completely and decreased the rate of rejoining of DNA strand breaks significantly; however, 3h after irradiation we observed no difference in the amount of DNA strand breaks between PARP inhibitor-treated and untreated cells. Twelve to 48 h after irradiation, an increase of ROS concentration was observed in irradiated cells and ROS levels in PARP inhibitor treated cells were significantly higher than in cells without inhibitor. Irradiated cells grown in the presence or absence of PARP inhibitor did not differ in the frequencies of apoptotic and necrotic cells or in the activity of caspases at 24, 48 and 72 h after irradiation. Poly(ADP-ribosylation) and inhibition of PARP1 appeared to modulate DNA strand break rejoining and influence the concentration of ROS in irradiated cells. PMID- 22321900 TI - Measuring hypoxia induced metal release from highly contaminated estuarine sediments during a 40 day laboratory incubation experiment. AB - Nutrient inputs to estuarine and coastal waters worldwide are increasing and this in turn is increasing the prevalence of eutrophication and hypoxic and anoxic episodes in these systems. Many urbanised estuaries are also subject to high levels of anthropogenic metal contamination. Environmental O(2) levels may influence whether sediments act as sinks or sources of metals. In this study we investigated the effect of an extended O(2) depletion event (40 days) on fluxes of trace metals (and the metalloid As) across the sediment-water interface in sediments from a highly metal contaminated estuary in S.E. Tasmania, Australia. We collected sediments from three sites that spanned a range of contamination and measured total metal concentration in the overlying water using sealed core incubations. Manganese and iron, which are known to regulate the release of other divalent cations from sub-oxic sediments, were released from sediments at all sites as hypoxia developed. In contrast, the release of arsenic, cadmium, copper and zinc was comparatively low, most likely due to inherent stability of these elements within the sediments, perhaps as a result of their refractory origin, their association with fine-grained sediments or their being bound in stable sulphide complexes. Metal release was not sustained due to the powerful effect of metal-sulphide precipitation of dissolved metals back into sediments. The limited mobilisation of sediment bound metals during hypoxia is encouraging, nevertheless the results highlight particular problems for management in areas where hypoxia might occur, such as the release of metals exacerbating already high loads or resulting in localised toxicity. PMID- 22321901 TI - Development of a relative risk model for evaluating ecological risk of water environment in the Haihe River Basin estuary area. AB - Ecological risk assessment for water environment is significant to water resource management of basin. Effective environmental management and systems restoration such as the Haihe River Basin require holistic understanding of the relative importance of various stressor-related impacts throughout the basin. As an effective technical tool for evaluating the ecological risk, relative risk model (RRM) was applied in regional scale successfully. In this study, the risk transfer from upstream of basin was considered and the RRM was developed through introducing the source-stressor-habitat exposure filter (SSH), the endpoint habitat exposure filter (EH) and the stressor-endpoint effect filter (SE) to reflect the meaning of exposure and effect more explicit. Water environment which includes water quality, water quantity and aquatic ecosystems was selected as the assessment endpoints. We created a conceptual model which depicting potential and effect pathways from source to stressor to habitat to endpoint. The Haihe River Basin estuary (HRBE) was selected as the model case. The results showed that there were two low risk regions, one medium risk region and two high risk regions in the HRBE. The results also indicated that urbanization was the biggest source, the second was shipping and the third was industry, their risk scores are 5.65, 4.71 and 3.68 respectively. Furthermore, habitat destruction was the largest stressor with the risk scores (2.66), the second was oxygen consuming organic pollutants (1.75) and the third was pathogens (1.75). So these three stressors were the main influencing factors of the ecological pressure in the study area. For habitats, open waters (9.59) and intertidal mudflat were enduring the bigger pressure and should be taken considerable attention. Ecological service values damaged (30.54) and biodiversity decreased were facing the biggest risk pressure. PMID- 22321902 TI - Rethinking passive transport: bus fare exemptions and young people's wellbeing. AB - Much recent public health research has emphasised the health impacts for young people of 'active travel' modes, typically defined as walking and cycling. Less research has focused on public transport modes. Drawing on qualitative data, we examine the links between bus travel and wellbeing in London, where young people currently have free bus travel. Our findings indicate that bus travel can be both a physically and socially active experience for young people. We suggest a more nuanced understanding of 'active travel' is now needed, alongside greater attention to urban public transport networks as key sites that impact on important determinants of wellbeing such as independent mobility and social inclusion. PMID- 22321903 TI - Understanding the non-stationary associations between distrust of the health care system, health conditions, and self-rated health in the elderly: a geographically weighted regression approach. AB - The goals of this study are to explore whether health condition is an antecedent extraneous factor for the relationship between health care system distrust and self-rated health among the elderly, and to investigate if the associations among these variables are place-specific. We used logistic geographically weighted regression to analyze data on an elderly sample residents in the Philadelphia metropolitan area. We found that the health conditions of the elderly account for the association between high distrust and poor/fair self-rated health and that the distrust/self-rated health relationship varied spatially. This finding suggests that a place-centered perspective can inform distrust/self-rated health research. PMID- 22321905 TI - Small metal soft tissue foreign body extraction by using 3D CT guidance: a reliable method. AB - OBJECTIVE: To introduce a useful and accurate technique for the locating and removal of small metal foreign bodies in the soft tissues. METHODS: Eight patients presented with suspected small metal foreign bodies retained in the soft tissues of various body districts. Under local anesthesia, 3-6 pieces of 5 ml syringe needles or 1 ml syringe needles were induced through three different planes around the entry point of the foreign bodies. Using these finders, the small metal FBs were confirmed under 3D CT guidance. Based on the CT findings, the soft tissues were dissected along the path of the closest needle and the FBs were easily found and removed according to the relation with the closest needle finder. RESULTS: Eight metal foreign bodies (3 slices, 3 nails, 1 fish hook, 1 needlepoint) were successfully removed under 3D CT guidance in all patients. The procedures took between 35 min and 50 min and the operation times took between 15 min and 25 min. No complications arose after the treatment. CONCLUSION: 3D CT guided technique is a good alternative for the removal of small metal foreign body retained in the soft tissues as it is relatively accurate, reliable, quick, carries a low risk of complications and can be a first-choice procedure for the extraction of small metal foreign body. PMID- 22321906 TI - Borderline ovarian tumours. AB - Borderline ovarian tumours account for 10-20% of all epithelial ovarian cancer. Historically, standard primary surgery has included borderline ovarian tumours, omentectomy, peritoneal washing and multiple biopsies. As one-third of borderline ovarian tumours are diagnosed in women under the age of 40 years, fertility sparing treatment has been more frequently used in the past 10 years. Fertility drugs are well tolerated in women with infertility after fertility-sparing surgery. Careful selection of candidates is necessary. Laparoscopic techniques can be used, but should be reserved for oncologic surgeons. This conservative treatment increases the rate of recurrence, albeit with no effect on survival. The pregnancy rate is nearly 50%, and most are achieved spontaneously. These women should be closely followed up. The question is whether this is acceptable from a gynaecologic oncologic point of view. For this reason, we will discuss recently published studies and gynaecologic oncologic concerns about the mode of fertility-sparing surgery and its consequences. PMID- 22321904 TI - Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). AB - BACKGROUND: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies against coagulation factor VIII and characterized by spontaneous hemorrhage in patients with no previous family or personal history of bleeding. Although data on several AHA cohorts have been collected, limited information is available on the optimal management of AHA. OBJECTIVES: The European Acquired Hemophilia Registry (EACH2) was established to generate a prospective, large scale, pan-European database on demographics, diagnosis, underlying disorders, bleeding characteristics, treatment and outcome of AHA patients. RESULTS: Five hundred and one (266 male, 235 female) patients from 117 centers and 13 European countries were included in the registry between 2003 and 2008. In 467 cases, hemostasis investigations and AHA diagnosis were triggered by a bleeding event. At diagnosis, patients were a median of 73.9 years. AHA was idiopathic in 51.9%; malignancy or autoimmune diseases were associated with 11.8% and 11.6% of cases. Fifty-seven per cent of the non-pregnancy-related cases were male. Four hundred and seventy-four bleeding episodes were reported at presentation, and hemostatic therapy initiated in 70.5% of patients. Delayed diagnosis significantly impacted treatment initiation in 33.5%. Four hundred and seventy-seven patients underwent immunosuppression, and 72.6% achieved complete remission. CONCLUSIONS: Representing the largest collection of consecutive AHA cases to date, EACH2 facilitates the analysis of a variety of open questions in AHA. PMID- 22321907 TI - Urinary symptoms and natural history of urinary continence after first-ever stroke--a longitudinal population-based study. AB - BACKGROUND: there are limited population-based data on urinary symptoms and the natural history of urinary incontinence after a first stroke. AIM: to study the prevalence of urinary symptoms, and the natural history and factors associated with urinary incontinence after first-ever stroke. METHODS: we administered a standardised urinary symptom questionnaire at 3 and 12 months after stroke to patients enrolled in the North-East Melbourne Stroke Incidence Study. Urinary symptoms and evolution of urinary incontinence were recorded. Logistic regression was used to model associations between baseline factors and incontinence at 12 months. RESULTS: more than 80% of survivors reported one or more abnormal urinary symptoms at 3 or 12 months, with nocturia most frequent. Incontinence was present in 43.5% of patients at 3 months, and 37.7% at 12 months, with urge incontinence being most common. Pre-stroke continence (P < 0.001) and female sex (P < 0.001) were independently associated with incontinence at 12 months, whereas the effect of greater stroke severity was magnified with advancing age (P for interaction = 0.05). CONCLUSION: the majority of survivors reported abnormal urinary symptoms early and late after stroke. Around a third of patients had incontinence at 12 months, with pre-stroke UI, age, female sex and stroke severity predicting its presence. PMID- 22321908 TI - Good memory as a predictor of falls: fact or artefact. AB - BACKGROUND: accurate classification of older people into fallers and non-fallers is crucial for falls research, but largely dependent on the accuracy of fall reporting by the participants. OBJECTIVE: to investigate the influence of memory in relation to fall reporting. SUBJECTS: five hundred community-dwelling adults aged 70-90 years. METHODS: memory and executive functioning were assessed using the Rey Auditory Verbal Learning and Trail Making test, respectively. Fall risk was estimated using the physiological profile assessment (PPA). Falls were recorded prospectively for 12 months using monthly falls diaries and follow-up phone calls as required. RESULTS: Spearman correlations showed that falls were significantly correlated to worse executive functioning, worse PPA scores and better memory. People with better memory had an increased risk of being classified as single fallers and multiple fallers, but not when reported injuries were included as part of the definition. CONCLUSION: good memory appears to influence the recording of falls in community-dwelling older people and likely reflects a reporting bias. In research studies, there may be value in using a combination of injurious falls and multiple falls when classifying people into faller and non-faller groups. PMID- 22321909 TI - The effects of noradrenergic blockade on extinction in humans. AB - The process of reconsolidation has attracted much attention because of its potential application for the treatment of psychiatric disorders. Here, we investigate a possible boundary condition of disrupting reconsolidation with the noradrenergic antagonist propranolol in humans. Reconsolidation can be initiated by retrieval of an acquired fear memory, which is in procedure equivalent to extinction training. If memory retrieval promotes the formation of a novel extinction memory trace, propranolol may interfere with extinction rather than with reconsolidation. Using a differential fear conditioning paradigm, we demonstrate that administration of propranolol (double-blind placebo controlled) prior to repetitive unreinforced CS presentations did not affect extinction at a physiological level (startle reflex and skin conductance). At a cognitive level, propranolol directly impaired extinction learning. These findings indicate that careful selection of timing parameters is essential to ensure that pharmacological agents interfere with the intended memory process to reduce fear. PMID- 22321910 TI - Endoscopic endonasal skull base surgery. AB - Skull base surgery has been transformed by the development of endoscopic techniques. Endoscopic procedures were first used for pituitary surgery and were then gradually extended to other regions. A wide range of diseases are now accessible to endoscopic skull base surgery. The major advantage of the endoscopic endonasal approach is that it provides direct anatomical access to a large number of intracranial and paranasal sinus lesions, avoiding the sequelae of a skin incision, facial bone flap or craniotomy, and brain retraction, which is inevitable with conventional neurosurgical incisions, resulting in decreased morbidity and mortality and, indirectly, decreased length of hospital stay and management costs. Moreover, the increasing number of publications in this field illustrates the growing interest in these techniques. This paper provides a review of endoscopic skull base surgery. The indications and general principles of endoscopic endonasal skull base surgery are described. Progress in exposure and especially reconstruction techniques is described. This progress now allows more extensive resections, while maintaining acceptable morbidity. The limits of this surgery are also discussed; in particular, although this surgery is often described as "minimally invasive", it is not completely devoid of morbidity. PMID- 22321911 TI - Extranodal NK/T-cell lymphoma, nasal type: report of 15 cases. AB - OBJECTIVES: To define the epidemiological and clinical features and complementary investigation findings of extranodal NK/T-cell lymphoma, nasal type and to discuss the diagnostic difficulties and the various treatment options. PATIENTS AND METHODS: This retrospective study was based on 15 patients with extranodal NK/T-cell lymphoma, nasal type, managed between 1990 and 2009. RESULTS: This series comprised 13 men and two women (sex ratio=6.5) with a mean age of 52 years (range: 35-81 years). The mean time to first consultation was 6 months. The most common symptoms were nasal obstruction (87%) and purulent nasal discharge (73%), followed by epistaxis (60%). Physical examination demonstrated the presence of a tumour of the nasal cavity in 11 patients. The diagnosis was confirmed by histological examination of a biopsy completed by immunohistochemistry. CT scan of the facial bones was performed in all patients of this series. The site of extranodal NK/T-cell lymphoma was essentially nasal (12 cases). Orbital extension was observed in four cases, associated with intracranial extension in two cases and osteolysis was observed in 11 patients. Lymphomas were classified as stage IE in 74% of cases and stage IIE in 26% of cases. Only one patient was lost to follow-up during treatment. Three patients died before any treatment. Treatment therefore concerned 12 patients. Stage IE lymphomas were treated by radiotherapy and/or chemotherapy. All stage IIE lymphomas were treated by chemotherapy alone. Stage IE patients had a better prognosis. CONCLUSION: Extranodal NK/T-cell lymphoma, nasal type, is an aggressive form of non-Hodgkin's lymphoma comprising specific clinicopathological characteristics. The addition of chemotherapy for advanced stages does not appear to improve survival compared radiotherapy alone, which remains the treatment of choice especially for localized stages. PMID- 22321912 TI - Imaging of non-operated cholesteatoma: clinical practice guidelines. AB - Middle ear cholesteatoma is an aggressive form of chronic otitis media requiring surgical therapy. The surgical strategy depends on the location of the lesion, its extensions to the middle ear and mastoid, the anatomical conformation of the tympanomastoid cavities and the health status of the patient (as well as his or her interest in aquatic leisure activities). For several years, imaging of the ear has been a routine test in the preoperative work-up of the disease. National guidelines for the topic "Imaging of non-operated middle ear cholesteatoma" were prepared in October 2010, for the annual congress of the French Society of Otolaryngology Head and Neck Surgery (SFORL), by a panel of experts from the SFORL, represented by the French Association of Otology and Neuro-otology (AFON), and the French Radiological Society (SFR), represented by the French Society of Head and Neck Imaging (CIREOL). These guidelines are presented in the present article. PMID- 22321913 TI - Predictive models for mutations in mismatch repair genes: implication for genetic counseling in developing countries. AB - BACKGROUND: Lynch syndrome (LS) is the most common form of inherited predisposition to colorectal cancer (CRC), accounting for 2-5% of all CRC. LS is an autosomal dominant disease characterized by mutations in the mismatch repair genes mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), postmeiotic segregation increased 1 (PMS1), post-meiotic segregation increased 2 (PMS2) and mutS homolog 6 (MSH6). Mutation risk prediction models can be incorporated into clinical practice, facilitating the decision-making process and identifying individuals for molecular investigation. This is extremely important in countries with limited economic resources. This study aims to evaluate sensitivity and specificity of five predictive models for germline mutations in repair genes in a sample of individuals with suspected Lynch syndrome. METHODS: Blood samples from 88 patients were analyzed through sequencing MLH1, MSH2 and MSH6 genes. The probability of detecting a mutation was calculated using the PREMM, Barnetson, MMRpro, Wijnen and Myriad models. To evaluate the sensitivity and specificity of the models, receiver operating characteristic curves were constructed. RESULTS: Of the 88 patients included in this analysis, 31 mutations were identified: 16 were found in the MSH2 gene, 15 in the MLH1 gene and no pathogenic mutations were identified in the MSH6 gene. It was observed that the AUC for the PREMM (0.846), Barnetson (0.850), MMRpro (0.821) and Wijnen (0.807) models did not present significant statistical difference. The Myriad model presented lower AUC (0.704) than the four other models evaluated. Considering thresholds of >= 5%, the models sensitivity varied between 1 (Myriad) and 0.87 (Wijnen) and specificity ranged from 0 (Myriad) to 0.38 (Barnetson). CONCLUSIONS: The Barnetson, PREMM, MMRpro and Wijnen models present similar AUC. The AUC of the Myriad model is statistically inferior to the four other models. PMID- 22321914 TI - Thrombo-prophylaxis in colorectal surgery: a National Questionnaire Survey of the members of the Association of Coloproctology of Great Britain and Ireland. AB - AIM: Available guidelines from the National Institute for Health and Clinical Excellence (NICE) and the Association of Coloproctology of Great Britain and Ireland (ACPGBI) recommend combined (medical + mechanical) thrombo- prophylaxis. A Cochrane Library review recommends self-administered low-molecular-weight heparin (LMWH) for 2-3 weeks following surgery. In the light of the recent guidelines from the ACPGBI and NICE, we undertook a National Questionnaire Survey to assess current thrombo-prophylaxis practice among colorectal surgeons in the UK. METHOD: A 10-item questionnaire was designed to enquire into the current management strategy of postoperative thrombo-prophylaxis. The postal questionnaire survey was sent to all 490 active consultant members of the ACPGBI. RESULTS: Of the 490 questionnaires sent, 259 (52.8%) were returned fully completed. Among these, all (100%) respondents reported the routine use of thrombo-prophylaxis, with 243 (93.8%) following departmental guidelines. Combined medical and mechanical prophylaxis was used by 247 (95.40%) respondents. A small number - 12 (4.6%) - used medical prophylaxis only. LMWH was the preferred medical-prophylactic agent of 243 (93.8%) repondents. The majority, 176 (68%), started thrombo-prophylaxis on admission and stopped it at discharge. Seventy-one (27.4%) respondents recommended thrombo-prophylaxis after hospital discharge for an average duration of 4-6 weeks, preferring graduated compression stockings followed by LMWH. CONCLUSION: The National Questionnaire Survey on thrombo prophylaxis demonstrated a high degree of concordance with the available guidelines, except for thrombo-prophylaxis to be continued postoperatively for a period of 28 days/4 weeks. PMID- 22321915 TI - Development and evaluation of a photographic atlas as a tool for dietary assessment studies in Middle East cultures. AB - OBJECTIVE: To assess the errors between estimates of amounts based on photographs and actual quantities of food presented to adults or eaten on the previous day. DESIGN: A photographic atlas was constructed by taking digital photographs of three pre-weighed portion sizes of 212 traditional Lebanese dishes. In a first approach, ten portions of real pre-weighed foods were assessed using the photographic atlas. In a second approach, the participants weighed all foods consumed at one meal and recalled the amount of food that was eaten the previous day using the photographic atlas. Differences between actual quantities and estimation were assessed using a signed rank test (P < 0.05). Spearman's correlation coefficients and bias (Bland-Altman plot) between the methods were calculated. SETTING: Lebanese university canteen and Lebanese homes. SUBJECTS: Forty adults (twenty males, twenty females) completed the first protocol and fifty adults (twenty-five males, twenty-five females) completed the second protocol; all were volunteers aged 21 to 62 years. RESULTS: Mean differences between actual and estimated portion sizes by photographs were between -13.1 % and +24.5 % when pre-weighed foods were presented, and between -10.4 % and +3.8 % when foods were consumed the day before. No significant differences were found between actual and estimated portion sizes except for three dishes (loubieh bil zeit, tabbouleh and yachnet bazella). Bland-Altman plots showed good agreement for all dishes with a negligible bias of -0.2 g between estimated and presented portions, and -6.3 g between estimated and eaten portions. CONCLUSIONS: In the Lebanese diet, food photographs seem a reliable tool for quantification of food portion sizes. PMID- 22321916 TI - Tailored internet-administered treatment of anxiety disorders for primary care patients: study protocol for a randomised controlled trial. AB - BACKGROUND: Internet-administered cognitive behavioural therapy (ICBT) has been found to be effective for a range of anxiety disorders. However, most studies have focused on one specific primary diagnosis and co-morbidity has not been considered. In primary care settings, patients with anxiety often suffer from more than one psychiatric condition, making it difficult to disseminate ICBT for specific conditions. The aim of this study will be to investigate if ICBT tailored according to symptom profile can be a feasible treatment for primary care patients with anxiety disorders. It is a randomised controlled trial aimed to evaluate the treatment against an active control group. METHODS: Participants with anxiety disorders and co-morbid conditions (N = 128), will be recruited from a primary care population. The Clinical Outcome in Routine Evaluation (CORE-OM) will serve as the primary outcome measure. Secondary measures include self reported depression, anxiety, quality of life and loss of production and the use of health care. All assessments will be collected via the Internet and measure points will be baseline, post treatment and 12 months post treatment. DISCUSSION: This trial will add to the body of knowledge on the effectiveness of ICBT for anxiety disorders in primary care. The trial will also add knowledge on the long term effects of ICBT when delivered for regular clinic patients TRIAL REGISTRATION: ClinicalTrials.gov: NCT01390168. PMID- 22321917 TI - Fear-avoidance model of chronic musculoskeletal pain: 12 years on. PMID- 22321918 TI - Intravenous neural stem cells abolish nociceptive hypersensitivity and trigger nerve regeneration in experimental neuropathy. AB - A nonphysiological repair of the lesioned nerve leading to the formation of neurinomas, altered nerve conduction, and spontaneous firing is considered the main cause of the events underlying neuropathic pain. It was investigated whether neural stem cell (NSCs) administration could lead to a physiological nerve repair, thus to a reduction of neuropathic pain symptoms such as hyperalgesia and allodynia in a well-established model of this pain (sciatic nerve chronic constriction injury [CCI]). Moreover, since we and others showed that the peripheral nerve lesion starts a cascade of neuroinflammation-related events that may maintain and worsen the original lesion, the effect of NSCs on sciatic nerve pro- and antiinflammatory cytokines in CCI mice was investigated. NSCs injected intravenously, when the pathology was already established, induced a significant reduction in allodynia and hyperalgesia already 3 days after administration, demonstrating a therapeutic effect that lasted for at least 28 days. Responses changed with the number of administered NSCs, and the effect on hyperalgesia could be boosted by a new NSC administration. Treatment significantly decreased proinflammatory, activated antiinflammatory cytokines in the sciatic nerve, and reduced spinal cord Fos expression in laminae I-VI. Moreover, in NSC-treated animals, a reparative process and an improvement of nerve morphology is present at a later time. Since NSC effect on pain symptoms preceded nerve repair and was maintained after cells had disappeared from the lesion site, we suggest that regenerative, behavioral, and immune NSC effects are largely due to microenvironmental changes they might induce at the lesion site. PMID- 22321919 TI - [Prevention and treatment of scars should be closely related to the study of the damage repair]. PMID- 22321920 TI - [Awareness of present status of study on hypertrophic scar]. PMID- 22321921 TI - [Effect of PRX-2 gene transferred by lipofectamine on the proliferation of human skin fibroblasts]. AB - OBJECTIVE: To explore the effects of PRX-2 gene transferred by lipofectamine on the human skin fibroblasts. METHODS: Normal human skin fibroblasts were cultured and PRX-2 gene was transferred by lipofectamine. The proliferation of fibroblasts was detected by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and flow cytometry. RESULTS: The proliferation of PRX-2-transfected fibroblasts was stronger than that of normal counterparts. There were fewer cells during G0-G1 period and more cells during S and G2-M periods. The proliferative index increased. CONCLUSION: The proliferation of fibroblasts may be modified by transfected PRX-2. Thus PRX-2 plays an important role during the healing of human skin wound. PMID- 22321922 TI - [Clinical efficacy of acne scar treatment with micro-plasma radio frequency]. AB - OBJECTIVE: To explore the efficacy of facial acne scars treatment with micro plasma radio frequency. METHODS: A total of 24 patients with facial acne scars underwent micro-plasma treatment for 3 - 5 times. And their efficacies were evaluated by the patient photographs before and 2 months after treatment. RESULTS: Facial acne scars were characterized by clouds of pitted scars with no specific shape. No difference appears in susceptibility between males and females. The overall improvement rate was 83.33%. The degree of improvement was as follows: significant 33.33%, moderate 25%, mild 25% and poor 16.67%. CONCLUSION: Micro-plasma technique is an effective therapy for acne scar. PMID- 22321923 TI - [Clinical and immunological relevance of antiphospholipid antibodies in patients with lymphoma]. AB - OBJECTIVE: To explore the prevalence, clinical and prognostic significance of anticardiolipin (aCL) IgG/M/A antibodies and anti-beta(2)-glycoprotein I (2-GPI) IgG/M/A antibodies in patients with lymphoma. METHODS: ACL IgG/M/A antibodies and anti-beta(2)-GPI IgG/M/A antibodies were determined by enzyme-linked immunosorbent assay (ELISA) in 129 lymphoma patients, 46 SLE patients, 38 rheumatoid arthritis (RA) patients, 24 primary Sjogren's syndrome (pSS) patients and 58 healthy controls. Laboratory and clinical features (thrombosis, event-free survival time, etc.) were analyzed retrospectively from the clinical database. RESULTS: (1) Elevated APL level was found in 52/129 lymphoma patients (40.3%): aCL IgG/M/A antibodies in 11.6% (15/129) and anti-beta(2)-GPI IgG/M/A antibodies in 32.6% (42/129) of lymphoma patients. There were significant differences between the prevalence and level of APL in lymphoma patients and healthy controls. But no difference was found between the lymphoma patients and SLE, RA or pSS patients. (2) APL was correlated with lymphoma derived from T or NK/T cells (P < 0.05). (3) No difference was found between the incidence of thrombosis in lymphoma patients with or without APL. (4) A strong negative correlation was found between the elevated APL and the event-free survival. CONCLUSION: APL is elevated in 40.3% of lymphoma patients. And it is significantly higher than that in healthy controls and similar with that in SLE, RA or pSS patients. APL is correlated with lymphoma cell origin and shortened event-free survival. PMID- 22321924 TI - [Clinical feature of cryptosporidium infection in HIV/AIDS patients with chronic diarrhea]. AB - OBJECTIVE: To investigate the clinical feature of cryptosporidium infection in HIV/AIDS patients with chronic diarrhea. METHODS: 253 Stool samples were collected from HIV/AIDS patients with chronic diarrhea during Nov.2009 to Dec.2010. The samples were concentrated by Formalin-Ethyl Acetate Sedimentation technique and stained by Modified acid-fast stain (AFS) for the identification of oocysts by microscopy. Divided the cases into three groups according to their CD4 cell counts (< 200, >= 200 and < 500, >= 500/ul); meanwhile the cases were divided into three groups by their age (20 - 35, 36 - 55, 56 - 69). Analyzed the groups by comparison. RESULTS: The total infection rate of Cryptosporidium in AIDS patients was 12.6% in 253 cases. CD4(+) T-lymphocyte counts was related to the infection rates of cryptosporidium, the difference was statistically significant (chi(2) = 10.33, P < 0.01): the infection rate were 20.4% (20/98), 9.23% (12/130), 0 (0/25) separately. In the 32 Cryptosporidium positive cases, 22 (68.8%) cases stood with diarrhea above 5 times per day, the three kind of CD4 counts level were separately 15 (15/20), 7 (7/12), 0. The difference was no statistically significant (P > 0.05). HIV/AIDS patients with chronic diarrhea who progressed during asymptomatic period, pre-AIDS period, AIDS period, had the infection rate of 0(0/7), 21.3% (19/89), 8.3% (13/157) respectively, the difference was statistically significant (chi(2) = 9.822, P < 0.01); 22 out of 32 Cryptosporidium positive cases in HIV patients were diagnosed with enteritis, the infection rate in urban area and rural area was 6.5% (7/104) and 16.8% (25/149) separately, the difference was statistically significant (chi(2) = 5.596, P < 0.05). Comparing different age groups, Cryptosporidium infection status were separately 7.3% (4/55), 13.4% (22/164), 17.6% (6/34). Each group's comparative difference was no statistically significant (chi(2) = 2.29, P > 0.05). CONCLUSION: The infection rate of cryptosporidium and clinical severity of cryptosporidium infection are statistically correlated with CD4(+) T-lymphocyte counts, with AIDS stage, with HIV associated proctitis. PMID- 22321925 TI - [Risk factors associated with twin pregnancy in double embryo transfer]. AB - OBJECTIVE: To explore the risk factors associated with twin pregnancy in double embryo transfer. METHODS: A retrospective analysis was performed for 2970 double embryo transfer cycles, including 1984 cycles of fresh embryo transfer and 986 cycles of frozen-thawed embryo transfer (FET). Multiple factor Logistic regression was used. The twin pregnancy rate was studied in group of age < 35 or age >= 35 years old, in group of zero, single or double high-quality embryos transferred and group of fresh embryo transfer or FET cycles. RESULTS: (1) There was a significantly negative correlation between women's age and twin pregnancy according to the analysis of multiple factor Logistic regression (P < 0.01). And a significantly positive correlation existed between the number of high-quality embryos transferred, FET and twin pregnancy (P < 0.01); (2) the twin pregnancy rate of both fresh embryo transfer and FET cycles was higher in group of age < 35 years than that in group of age >= 35 years (16.0% vs 8.0%, P < 0.01; 26.9% vs 14.2%, P < 0.01); (3) the twin pregnancy rate of fresh embryo transfer cycles with double high-quality embryos transferred was higher than that with zero or single high-quality embryos transferred (19.1% vs 5.4%; 19.1% vs 11.0%, P < 0.01); the twin pregnancy rate of FET cycles with double high-quality embryos transferred was also higher than that with zero or single high-quality embryos transferred (32.7% vs 10.8%; 32.7% vs 20.7%, P < 0.01); (4) the twin pregnancy rate of FET cycles was significantly higher than that of fresh embryo transfer cycles (24.7% vs 14.9%, P < 0.01). CONCLUSION: Women's age, the number of high quality embryos transferred and FET are risk factors associated with twin pregnancy. At reproductive centers with a mature technique of FET, we recommend performing single high-quality embryo transfer in FET cycles to reduce the occurrence of twin pregnancy. PMID- 22321926 TI - [Economics analysis of endometriosis and adenomyosis surgeries]. AB - OBJECTIVE: To explore the hospital expenses and hospital stay of surgical management for endometriosis and adenomyosis. METHODS: The average hospital expenses and average hospital stay were compared for a total of 12003 patients of endometriosis and adenomyosis confirmed operatively at our hospital from January 1994 to December 2008. And the relevant factors consisted of surgical phases, pathological types, surgical approaches, surgical routes, definite procedures and age groups. RESULTS: The average hospital expenses were significantly higher than average gynecologic surgical expenses (RMB 7073 vs RMB 6847, P < 0.01) while and the average hospital stays significantly shorter than the latter (6.8 vs 8.6 days, P < 0.01). The periods of 2006 - 2008 and 1994 - 1996 had significantly different average hospital expenses (RMB 7853 vs RMB 3382, P < 0.01) and average hospital stay (6.4 vs 9.5 days, P < 0.01). Multivariate analysis showed age was the most important correlated factor for the hospital expenses of endometriosis and adenomyosis surgeries (all P < 0.01). And surgical approach was one of the most important factors for hospital stay (all P < 0.01). CONCLUSION: Adenomyosis has the highest cost and younger endometriosis patients carry the lowest economic burden. Laparoscopy and conservative surgery may reduce the economic burden of endometriosis and adenomyosis operations. PMID- 22321927 TI - [Application of B type natriuretic peptide in fluid therapy after major abdominal operations]. AB - OBJECTIVE: To evaluate the values of serum level of B type natriuretic peptide level (BNP) in the prediction of fluid overloading after major abdominal operations. METHODS: The levels of BNP were dynamically monitored in 105 patients during peri-operative period from February 2009 to November 2010. Then comparisons were made with age and the volume of positive fluid balance. RESULTS: A post-operative elevation of BNP was observed in all cases. Among them, the peak level of BNP exceeded 100 ng/L in 32 patients while a normal peak level of BNP was found in 73 patients. Congestive heart failure (CHF) was diagnosed in 5 patients. At every single time point, the volume of positive fluid balance showed no significant difference among the peak level of BNP < 100 ng/L, >= 100 ng/L and CHF patients (all P > 0.05). In the group of peak level of BNP >= 100 ng/L, the patients received post-operative diuretic and the urine volume increased significantly [(280 +/- 55) ml/h vs (82 +/- 22) ml/h, P < 0.05]. However, in the group of the peak level of BNP < 100 ng/L, the urine volume showed no difference after dosing of diuretic [(95 +/- 18) ml/h vs (89 +/- 24) ml/h, P > 0.05]. Single variance analysis showed that the elevated level of BNP was associated with age and concurrent cardiopulmonary diseases (R = 0.87, P = 0.006) but not with the volume of positive fluid balance (R = 0.43, P = 0.080). And multiple variance analysis showed the similar results (R = 0.59, P = 0.020, R = 0.38, P = 0.120). In all cases, the levels of BNP peaked at 12 hours post-operation. However, body weight and the volume of positive fluid balance peaked at 18 - 24 hours post operation. CONCLUSION: The post-operative level of BNP is associated with age. And a highly elevated level of BNP may predict the occurrence of fluid overloading. An early peak of BNP value may be used as a cut-off point of positive and negative fluid balances. PMID- 22321928 TI - [Effects of splenic flexure and sigmoid colon variation on the types of anastomosis after left colectomy]. AB - OBJECTIVE: To explore the effects of splenic flexure and sigmoid colon variation on anastomosis after left colectomy. METHODS: The clinical data of 76 descending colon patients were collected retrospectively from March 2004 to April 2011 at our hospital. Statistical analysis was performed for the types of splenic flexure and sigmoid colon with regards to the choice of anastomosis. RESULTS: There were mesenteric type (n = 55), mobile type (n = 7) and adhesive type (n = 14) for splenic flexure. And among 61 regular types, 15 were of variable type for sigmoid colon variation. There was significant difference of anastomosis between the types of sigmoid colon variation [43 (78.2%) vs 5 (71.4%) vs 9 (64.3%), P > 0.05] while no significant difference existed between the types of splenic flexure [I type 56(91.8%) vs II type 1 (14.3%), III or IV type 0, P < 0.05]. CONCLUSION: A clinician should pay more attention to the types of sigmoid colon variation. And it helps to select the right approach of anastomosis after left colectomy. PMID- 22321929 TI - [Feasibility and safety of acute hypervolemic hemodilution in neurosurgical patients]. AB - OBJECTIVE: To evaluate the preoperative effects of acute hypervolemic hemodilution (AHH) on intracranial pressure, cerebral oxygen supply-demand balance and cardiovascular functions of neurosurgical patients. METHODS: Approved by hospital ethics committee, a total of 80 ASA grade I/II patients at our hospital during 2009, of either gender aged 18-60 yrs, undergoing elective craniotomy were recruited. The subjects were randomly divided equally into 2 groups: group H (hemodilution) and group C (control) (n = 40 each). After induction, 6% hydroxyethyl starch solution was infused at the rate of 24 ml*kg( 1)*h(-1) in group H, while patients in group C received compound electrolyte solution at the rate of 6 ml*kg(-1)*h(-1). Central venous pressure (CVP), cardiac output index (CI), stroke volume variation (SVV) and cerebral spinal fluid pressure (CSFP) were recorded at the following time points: T(Base) (before induction), T(0) (after induction and hemodynamic stabilization), T(30) (after infusion for 30 min) and T(60) (after infusion for 60 min). Blood samples from radial artery and jugular bulb were collected and calculated for systemic vascular resistance index (SVRI) and cerebral oxygen uptake rate (CERO(2)). The dosing frequency of vasoactive drugs was also recorded. RESULTS: CI in group H was significantly higher than that in group C (P < 0.01). No significant difference was found in both SjvO(2) and CERO(2) between groups and among different points of time (P > 0.05). At the end of AHH, CVP and CSFP were (12 +/- 2.2) mm Hg and (20.0 +/- 2.1) mm Hg respectively. They were significantly higher than that in group C (P < 0.01). CONCLUSION: Preoperative AHH in craniotomy will increase CI and maintain the balance of cerebral oxygen supply. But its clinical application is limited in the patient with high intracranial pressure due to the simultaneous increases in CVP and CSFP. PMID- 22321930 TI - [Safety and efficacy of enteral nutritional suspension (TPF-FOS) JEVITY in acute stroke]. AB - OBJECTIVE: To evaluate the safety and efficacy of enteral nutritional suspension (TPF-FOS) JEVITY in acute stroke patients. METHODS: A multicenter, prospective, post-marketing observational study was conducted. A total of 103 acute stroke patients with dysphagia received a 10-day regimen of enteral nutritional suspension (TPF-FOS) JEVITY via nasal gastric tube feeding. The parameters of serum prealbumin, serum albumin and percentage of abnormal blood glucose were evaluated and compared. The incidence of adverse events was recorded. The data were analyzed by paired t-test. RESULTS: At the end of the study in comparison with the baselines, the serum prealbumin increased significantly (213 mg/L +/- 56 mg/L vs 219 mg/L +/- 66 mg/L) and serum albumin decreased markedly (38 g/L +/- 5 g/L vs 36 g/L +/- 5 g/L) but stayed stable during tube feeding. No significant changes were found in percentage of abnormal blood glucose (40.78% vs 38.76%), body mass index (23.1 kg/m(2) +/- 3.0 kg/m(2) vs 22.8 kg/m(2) +/- 2.9 kg/m(2)) and C-reactive protein (13 mg vs 14 mg). Only 18 adverse events were related with the study product. And most of them were gastrointestinal reactions. CONCLUSION: Enteral nutritional suspension (TPF-FOS) JEVITY may increase the level of serum prealbumin in acute stroke patients and improve the patient nutritional status. With a low incidence of adverse events, it is a preferred option for enteral nutrition formulas in stroke. PMID- 22321931 TI - [Effect of fascia iliaca compartment block with ropivacaine on early analgesia in children with development dislocation of the hip received salter arthroplasty treatment]. AB - OBJECTIVE: To observe the efficacy and safety of fascia iliaca compartment block (FICB) with 0.2% ropivacaine in the early analgesia of children with development dislocation of the hip (DDH) undergoing Salter arthroplasty. METHODS: Approved by the hospital ethics committee, a total of 64 DDH children were divided randomly into 2 groups: group F (FICB with ropivacaine 0.2%, 1 ml/kg, max. 30 ml) and group C (FICB with 0.9% normal saline 1 ml/kg, max. 30 ml). The intra-operative doses of fentanyl, PACU (post-anesthesia care unit), CRIES pain score at 1, 4 and 24 h postoperatively, patient satisfaction score and side effects were recorded. RESULTS: The intra-operative doses of fentanyl and PACU were lower. Pain scores at 1, 4 and 24 h postoperatively were lower. And the patient satisfaction score was significantly higher in the FICB group. CONCLUSION: The administration of ropivacaine (0.2%) for FICB in the early analgesia of DDH children has the advantages of safety, precision, long-lasting and convenience. PMID- 22321932 TI - [Diagnostic significance of spinal cord conduction velocity in the diagnosis of central lesions in subacute combined degeneration]. AB - OBJECTIVE: To study explore the roles of spinal cord conduction velocity (SCCV) test in the diagnosis of spinal lesions in patients with subacute combined degeneration (SCD) of spinal cord and examine the values of SCCV in the localization of spinal lesions. METHODS: A total of 22 SCD patients recruited from 2005 to 2010 at our hospital underwent the SCCV test, the somatosensory evoked potential (SEP) test and MRI in spinal cord respectively. The results of SCCV were compared with those of SEP and MRI. RESULTS: There were 16 males and 6 females with an average age of (56 +/- 13) years old (range: 28 - 84). All SCD patients underwent the examinations of SCCV and spinal MRI. And 18 patients received the test of SEP. The abnormalities of SCCV test were 81.8% (18/22) and those of MRI and SEP 13.6% (3/22) and 72.2% (13/15) respectively. The results of SCCV and spinal MRI were both abnormal in 3 patients. Nineteen patients had normal MRI while 18 had abnormal SCCV results. CONCLUSION: The early electrophysiological abnormalities in spinal cord of SCD patients may be detected objectively by SCCV. They appear earlier than those of pathological and imaging findings. The abnormal rates of SCCV are much higher than those of spinal MRI. The SCCV test can also help to localize the lesions in spinal cord of SCD patients. It may provide an objective diagnostic basis for the lesions of spinal cord of SCD patients at an early stage. PMID- 22321933 TI - [Identification and 7.0 T magnetic resonance imaging of murine bone marrow derived endothelial progenitor cells]. AB - OBJECTIVE: To label murine bone marrow derived endothelial progenitor cells (EPCs) with nanometer magnetic probe (Resovist) and perform magnetic resonance (MR) imaging on these labeled cells. METHODS: Murine bone marrow derived mononuclear cells (MNCs) were isolated. And EPCs were selected by adherence method, expanded and incubated with Resovist. Cell surface markers were detected with immunofluorescence. Endocytosis of Dil-AcLDL (dil-labeled acetylated low density lipoprotein) and in vitro binding of FITC-UEA-1 (fluorescein isothiocyanate-vicia ervilia lectin-1) were also detected. Intracellular iron was detected by Prussian blue dye. Different quantities of labeled cells were visualized by 7.0T MR. RESULTS: The cultured cells expressed the endothelial cell markers of CD31 and KDR with immunofluorescence. The cells could bind UEA and endocytosis LDL. Iron particles could be observed in cells with Prussian blue dying and the ratio of label was approximately 100 percent. The Resovist labeled cells showed a lower signal than the non-labeled counterparts on T(2)(*)WI (weighted imaging), especially the 1*10(6) labeled cells showed the lowest signal. CONCLUSIONS: Murine bone marrow derived MNCs can be induced into EPCs and Resovist can label them effectively. The labeled cells can be visualized in vitro by 7.0T MR for cellular therapy and real time in vivo monitor. PMID- 22321934 TI - [Effects of receptor interacting protein 140 on the biological activity of glia cells]. AB - OBJECTIVE: To explore the effects of receptor interacting protein (RIP) 140 gene overexpression upon the in vitro proliferation, apoptosis, invasion and migration of microglioma cells. METHODS: The BV-2 RIP140 overexpression model (BV-2-1) was constructed by Lipofection and G418 selection, then validated by real-time PCR and Western blotting. The proliferation, apoptosis, invasion and migration potencies were compared between BV-2-1 and its parents by 3-(4,5-dimethylthiazol 2-yl)-2,5-diphenyl tetrazolium (MTT) assay, flow cytometry and Transwell chamber. RESULTS: The BV-2-1 model was successfully constructed. Compared to those of the BV-2 group, the RIP140 mRNA and protein expression levels of BV-2-1 were markedly higher than those of the BV-2 group (t = 49.794, P < 0.01). MTT assay showed that the absorbance values in the BV-2 group were 1.157 +/- 0.013, 1.679 +/- 0.005 and 2.609 +/- 0.008 at 24, 48, and 72 hours respectively. And those were 0.929 +/- 0.013, 1.188 +/- 0.008 and 1.528 +/- 0.012 in the BV-2-1 group respectively. The proliferation at the time points of 48 and 72 hours of the BV-2-1 group were significantly lower than that of the BV-2 group (t = 6.058 and 9.245, both P < 0.01). Annexin-V staining showed that there were significant differences in the apoptosis rates between the BV-2 and BV-2-1 cells [(5.35 +/- 0.23)% vs (3.46 +/- 0.45)%, t = 6.619, P = 0.003)]. Transwell assay showed that the invaded cell number of the BV-2-1 group was 166 +/- 43. And it was obviously higher than that of the BV-2 group (93 +/- 32, t = 3.403, P = 0.007). Transwell assay also showed that the migrated cell number of BV-2 cells was 101 +/- 25. And the migration potency of the BV-2-1 group (202 +/- 50) was significantly stronger than that of the BV-2 group (t = 4.104, P = 0.002). CONCLUSION: RIP140 effectively inhibits the proliferation and facilitates the apoptosis of microglioma cells. And it may effectively facilitate the in vitro invasion and migration of microglioma cells. PMID- 22321935 TI - [Aberrant methylation of T-cadherin gene in human esophageal carcinoma cells]. AB - OBJECTIVE: To explore the methylation status of T-cadherin promoter region in human esophageal carcinoma cell lines EC1 and EC109 and elucidate the effects of 5-azacytidine-2'-deoxycytidine (5-Aza-CdR) on their abilities of proliferation and invasion, the methylation status and the expression of T-cadherin. METHODS: The expression level of T-cadherin was measured by Western blot. And the methylation status of T-cadherin promoter region was analyzed by methylation specific PCR (polymerase chain reaction), separately before and after a treatment of demethylating agent 5-Aza-CdR. RESULTS: The T-cadherin gene was hypermethylated in EC109 cells but semi-methylated in EC1 cells. After a treatment of 5-Aza-CdR, T-cadherin gene methylation was reversed. And the gene expression was strongly up-regulated in both cells. 5-Aza-CdR could decrease the proliferation and effectively inhibit the ability of cell invasion (P < 0.01). CONCLUSION: The aberrant methylation in promoter region is an important mechanism of T-cadherin gene inactivation in human esophageal carcinoma cells. 5-Aza-CdR can increase the expression of T-cadherin by a reversal of hypermethylation and effectively inhibit the proliferation and invasion of tumor cells. PMID- 22321936 TI - Differential regulation of intracellular factors mediating cell cycle, DNA repair and inflammation following exposure to silver nanoparticles in human cells. AB - BACKGROUND: Investigating the cellular and molecular signatures in eukaryotic cells following exposure to nanoparticles will further our understanding on the mechanisms mediating nanoparticle induced effects. This study illustrates the molecular effects of silver nanoparticles (Ag-np) in normal human lung cells, IMR 90 and human brain cancer cells, U251 with emphasis on gene expression, induction of inflammatory mediators and the interaction of Ag-np with cytosolic proteins. RESULTS: We report that silver nanoparticles are capable of adsorbing cytosolic proteins on their surface that may influence the function of intracellular factors. Gene and protein expression profiles of Ag-np exposed cells revealed up regulation of many DNA damage response genes such as Gadd 45 in both the cell types and ATR in cancer cells. Moreover, down regulation of genes necessary for cell cycle progression (cyclin B and cyclin E) and DNA damage response/repair (XRCC1 and 3, FEN1, RAD51C, RPA1) was observed in both the cell lines. Double strand DNA damage was observed in a dose dependant manner as evidenced in gammaH2AX foci assay. There was a down regulation of p53 and PCNA in treated cells. Cancer cells in particular showed a concentration dependant increase in phosphorylated p53 accompanied by the cleavage of caspase 3 and PARP. Our results demonstrate the involvement of NFkappaB and MAP kinase pathway in response to Ag np exposure. Up regulation of pro-inflammatory cytokines such as interleukins (IL 8, IL-6), macrophage colony stimulating factor, macrophage inflammatory protein in fibroblasts following Ag-np exposure were also observed. CONCLUSION: In summary, Ag-np can modulate gene expression and protein functions in IMR-90 cells and U251 cells, leading to defective DNA repair, proliferation arrest and inflammatory response. The observed changes could also be due to its capability to adsorb cytosolic proteins on its surface. PMID- 22321937 TI - Determination of the relationship between radon anomalies and earthquakes in well waters on the Aksehir-Simav Fault System in Afyonkarahisar province, Turkey. AB - Radon concentrations were measured in water of 4 wells on the Aksehir-Simav Fault System (ASFS) in Afyonkarahisar province from August 2009 to September 2010 and the relationship between radon anomalies and earthquake magnitudes was examined. Anomalous decreases in radon concentrations in the wells were observed to precede the earthquakes of magnitudes ranging from 2.6 M to 3.9 M. The correlation coefficients (R(2)) were 0.79, 0.93, 0.98 and 0.90 for the wells from 1 to 4, respectively, indicating that radon minima and earthquake magnitude were well correlated and suggesting that the groundwater radon, when observed at suitable sites, can be a sensitive tracer for strain changes in crust associated with earthquake occurrences. The relationship between the two parameters can be further improved as additional radon anomalies precursor to possible large earthquakes are recorded in the wells located on the ASFS in the future. This study strongly suggests that the continuous observations of radon concentrations in well water, especially at well 3, should be carried forward. PMID- 22321938 TI - The evolution of HLA-B*3501 binding affinity to variable immunodominant NP(418 426) peptides from 1918 to 2009 pandemic influenza A virus: a molecular dynamics simulation and free energy calculation study. AB - Virus-specific cytotoxic T lymphocytes contribute to the control of virus infections including those caused by influenza viruses. However, during the evolution of influenza A viruses, variations in cytotoxic T lymphocytes epitopes have been observed and it will affect the recognition by virus-specific cytotoxic T lymphocytes and the human virus-specific cytotoxic T lymphocytes response in vitro. Here, to gain further insights into the molecular mechanism of the virus specific cytotoxic T lymphocytes immunity, the class I major histocompatibility complex-encoded HLA-B*3501 protein with six different NP(418-426) antigenic peptides emerging from 1918 to 2009 pandemic influenza A virus were studied by molecular dynamics simulation. Dynamical and structural properties (such as atomic fluctuations, solvent-accessible surface areas, binding free energy), based on the solvated protein-peptide complexes, were compared. Free energy calculations emphasized the important role of the secondary anchors (positions 2 and 9) in influencing the binding of MHC-I with antigenic non-apeptides. Furthermore, major interactions with peptides were gained from HLA-B*3501 residues: Tyr7, Ile66, Lys146, Trp147, and Tyr159. Detailed analysis could help to understand how different NP(418-426) mutants effectively bind with the HLA B*3501. PMID- 22321939 TI - Functional foods and their expanding applications in the improvement of human health. PMID- 22321940 TI - Microbial production and environmental applications of Pd nanoparticles for treatment of halogenated compounds. AB - New biological inspired methods were recently developed to recover precious metals from waste streams and to concomitantly produce palladium nanoparticles on bacteria, that is, bio-Pd. This technology offers a variety of opportunities, as the process can considered to be green, tunable, affordable and scalable. The nanoparticle formation and the specific role of the bacteria in the reclamation process are highlighted. The effective performance of bio-Pd as catalyst in dehalogenation reactions, as well as in hydrogenation, reduction and CC coupling reactions has been extensively described in literature. Especially dehalogenation of environmental contaminants represents a promising market for application of bio-Pd. Therefore, several treatment technologies based on bio-Pd in the different environmental compartments are considered and domains, in which bio-Pd can be used at full scale are described. Finally, the perspectives for implementation of the bio-Pd technology in the future are set forward. PMID- 22321941 TI - Nanorotors and self-assembling macromolecular machines: the torque ring of the bacterial flagellar motor. AB - The bacterial flagellar motor (BFM) is a self-assembling rotary nanomachine. It converts a flux of cations into the mechanical rotation of long filaments that propel bacteria through viscous media. The BFM contains a torque-generating ring that is complete with molecular machinery known as the switch complex that allows it to reverse directions. With four billion years of optimization, the BFM probably offers the pinnacle of sophisticated nanorotor design. Moreover as one of the best-characterized large biomolecular complexes, it offers the potential for convergence between nanotechnology and biology, which requires an atomic level understanding of BFM structure and function. This review focuses on current molecular models of the reversible BFM and the strategies used to derive them. PMID- 22321942 TI - Microscale and nanoscale compartments for biotechnology. AB - Compartmentalization is essential in the organization of biological systems, playing a fundamental role in modulating biochemical activity. An appreciation of the impact that biological compartments have on chemical reactions and an understanding of the physical and chemical phenomena that affect their assembly and function have inspired the development of synthetic compartments. Organic compartments assembled from amphiphilic molecules or derived from biological materials, have formed the basis of initial work in the field. However, inorganic and hybrid organic-inorganic compartments that capitalize on the optical and catalytic properties of metal and semiconductor materials are emerging. Methods for arraying these microcompartment and nanocompartment materials in higher order systems promise to enable the scaling and integration of these technologies for industrial and commercial applications. PMID- 22321943 TI - [Emergency care in the autonomous regions of Spain. Improvement in pre-hospital emergency care and welfare coordination. SESPAS Report 2012]. AB - The present article describes the general organization of pre-hospital emergency care in the autonomous regions and provides data on activity corresponding to 2010, drawn from the information available in the Primary Care Information System of the Ministry of Health, Social Policy and Equality. Emergency care is provided through various organizational structures covering 24-hour periods. Family medicine attended 17.8 million emergency consultations and nursing attended 10.2 million (year 2010, 14 autonomous communities, 79.7% of the National Health System population). Emergency department utilization ranged between 0.11 and 0.83 urgent family physician consultations per inhabitant/year and between 0.05 and 0.57 nursing consultations per inhabitant/year. Any reform in the management of pre-hospital emergency care will involve organizational changes and aims to produce measurable improvements in healthcare coordination. In the new organizational designs, most of the responsibility lies with human resources in order to achieve the new goals for the future aims to be presented in an operational teamwork structure. Undoubtedly, the main challenge is to achieve optimal coordination with other welfare levels, including the police, social services, nursing homes, etc. If optimal care of the population needs to count on the efforts of all these groups, mobility, individual differences, consistent achievement of high standards, and -most of all- the use of these services by citizens will determine the final result. The results can be quantified in various ways, but evaluation should concentrate on the resources used, the degree of satisfaction among all the parties involved and optimal management of demand, which will help to disseminate the need for a rational resource use. PMID- 22321944 TI - [How should population health be approached? SESPAS Report 2012]. AB - The health of the population largely depends on environmental factors, raising the issue of what the role of health professionals, particularly those in public health and primary care, should be in the planning of objectives and actions for improvement. The present article proposes a trajectory, starting with knowledge of the community's strong points in health and its needs, and ending with taking action. This trajectory requires discussion on how information can be transformed into action. We analyze the current situation and its strengths and weaknesses, and make proposals for the entire process: from information to action. Information is more than just the available data gathered from different sources; it is also knowledge of those who belong to the community or are very close to it. This perspective should include both health deficits and health assets. This information should be used not only by health professionals, but by all those in a position to influence the determinants of health. Finally, when considering the actions required to improve the health of a community, we emphasize the benefits of health promotion, in the genuine sense of the term, by reflecting on effectiveness and efficiency. The question of whether the failure of an intervention to improve health is due to the futility of the action, or to be action being undertaken in an inefficient way, is discussed. PMID- 22321945 TI - [Social inequalities in health and primary care. SESPAS Report 2012]. AB - The health system is a social determinant of health. Although not the most important determinant of health, the health system's potential contribution to reducing social inequalities in health should not be underestimated. Due to its characteristics, primary health care is well placed to attain equity in health. To make progress in achieving this goal, the main measures to be considered are the removal of barriers to access to services, the provision of care proportionate to need, and engagement in intersectoral work. This article reviews the background and framework for action to tackle social inequalities in health and provides a summary of the primary health care actions that could help to reduce social inequalities in health and are mentioned in the most important national and international documents on health policy. We hope to stimulate debate, promote research in the field and encourage implementation. The proposals are grouped in the following five intervention lines: information systems; participation; training; intersectoral work; and reorientation of health care. Each intervention is ordered according to its targets (population and civil society; primary health team; health center and health area management; and health policy decision-makers). PMID- 22321946 TI - Temperature rating prediction of Tibetan robe ensemble based on different wearing ways. AB - Each piece of Western clothing has a unique temperature rating (TR); however, based on different wearing ways, one Tibetan robe ensemble can be used in various environments of the Tibetan plateau. To explain this environmental adaptation, thermal insulations and TR values of Tibetan robe ensembles in three typical wearing ways were measured by manikin testing and wearing trials, respectively. The TR prediction models for Tibetan robe ensembles were built in this research. The results showed that the thermal insulations of Tibetan robe ensembles changed from 0.26 clo to 0.91 clo; the corresponding TRs ranged from 9.90 degrees C to 16.86 degrees C because of different wearing ways. Not only the thermal insulation, but also the ways of wearing Tibetan robes was important to determining their TR values. The three TR models and a triangle area for each piece of Tibetan clothing explained its positive adaptation into the environment; this was different from the current TR models for Western clothing. PMID- 22321947 TI - Evaluation of new cellulose-based chiral stationary phases Sepapak-2 and Sepapak 4 for the enantiomeric separation of pesticides by nano liquid chromatography and capillary electrochromatography. AB - Two novel polysaccharide-based chiral stationary phases (CSPs), known as Sepapak 2 (cellulose tris(3-chloro-4-methylphenylcarbamate)) and Sepapak-4 (cellulose tris(4-chloro-3-methylphenylcarbamate)), have been evaluated in this work for the chiral separation of a group of 16 pesticides including herbicides, insecticides and fungicides. The optimization of the mobile phase employed in nano-liquid chromatography (nano-LC) enabled the chiral separation of seven pesticides on Sepapak-2 and of nine pesticides on Sepapak-4. Due to the fact that Sepapak-4 gave better results, this column was selected to compare nano-LC and capillary electrochromatography (CEC) under the same conditions that consisted in the use of a 90/9/1 (v/v/v) ACN/H2O/ammonium formate (pH 2.5) background electrolyte (BGE). As expected, both the efficiency and the chiral resolution obtained in CEC experiments were higher than in nano-LC for all the analyzed compounds. The analytical characteristics of the CEC developed methodology were evaluated in terms of linearity, LODs, LOQs, precision, selectivity, and accuracy allowing its application to the quantitation of metalaxyl and its enantiomeric impurity in a commercial fungicide product marketed as enantiomerically pure (metalaxyl-M) and in soil and tap water samples after solid phase extraction (SPE). The determined amount of metalaxyl-M was found to be a 26% above the labeled content and it contained an enantiomeric impurity of a 3.7% of S-metalaxyl was determined. PMID- 22321948 TI - Preparation and electrophoretic separation of Bodipy-Fl-labeled glycosphingolipids. AB - Several glycosphingolipids were labeled with the fluorphore Bodipy-Fl and analyzed using capillary electrophoresis with laser-induced fluorescence detection. GM1-, LacCer-, and Cer-Bodipy-Fl were prepared through acylation using the N-hydroxysuccinimide ester of Bodipy-Fl. Several other glycosphingolipids including GT1a-, GD1a-, GM2-, GM3-, GD3-, and GlcCer-Bodipy-Fl were enzymatically synthesized. Micellar electrokinetic capillary chromatography with a TRIS/CHES/SDS/alpha-cyclodextrin buffer produced better separation than an established borate/deoxycholate/methyl-beta-cyclodextrin buffer. The nine Bodipy Fl-labeled glycosphingolipid standards were separated in under 5 min, theoretical plate counts were between 640,000 and 740,000, and the limit of detection was approximately 3 pM or 240 ymol analyte injected onto the capillary. PMID- 22321949 TI - Strategies for the analysis of highly reactive pinacolboronate esters. AB - Pinacolboronate esters (or boronic acid, pinacol esters) are widely used in the Suzuki coupling reaction to connect organic building blocks for the total synthesis of complex molecules. The 2-aminopyrimidine-5-pinacolboronate ester was used as a starting material in the synthesis of a development compound, necessitating a chromatographic purity method to assess its quality. This aryl pinacolboronate ester posed unique analytical challenges due to its facile hydrolysis to the corresponding boronic acid, which is nonvolatile and poorly soluble in organic solvents. This made GC and normal-phase HPLC analysis unsuitable. In reversed-phase mode, typical sample preparation and analysis conditions promoted rapid sample degradation to the boronic acid. To overcome these challenges, unconventional approaches were necessary in order to stabilize 2-aminopyrimidine-5-pinacolboronate ester, adequately solubilize its boronic acid, and produce acceptable separation and retention. The final method employed non-aqueous and aprotic diluent, and a reversed-phase separation using highly basic mobile phases (pH 12.4) with an ion pairing reagent. These strategies were successfully applied to several other reactive pinacolboronate esters for purity analysis, demonstrating broad applicability to this unique class of compounds. PMID- 22321950 TI - Automated approach for the rapid identification of purification conditions using a unified, walk-up high performance liquid chromatography/supercritical fluid chromatography/mass spectrometry screening system. AB - Integration of supercritical fluid/mass spectrometry (SFC/MS) and reversed phase liquid (HPLC/MS) chromatographic screening techniques into a single chromatographic system and utilized in "walk up" mode, enabled us to produce an orthogonal data set for selecting purification conditions for medicinal chemistry compounds. To streamline the overall workflow, we also demonstrate the use of automated batch data processing of individual data files to identify suitable separation conditions without user intervention. We have addressed the chromatographic challenges that hinder the identification of the intended target and thus the selection of ideal purification conditions. For instance, multiple component-of-interest (COI) peaks, co-elution of impurities with the COI, and chromatographic suitability factors such as retention times and peak shapes are all important considerations when selecting appropriate methods for purification and, therefore, are bottlenecks to an automated approach. Since SFC and HPLC data were collected in parallel from separate instruments in our workflow, the time required for the separation scientist to analyze acquired data from both systems was a time-limiting factor. To reduce data processing time and accelerate or "FastTrack" samples to purification, two unique and automated solutions were introduced. We describe the implementation of an integrated, multi-column, walk up HPLC/SFC/MS system, and the implementation of an intelligent, automated method selection application which uses advanced data evaluation criteria to selectively score and identify the most practical separation conditions for SFC/MS and HPLC/MS methodologies. PMID- 22321951 TI - Superparamagnetic surface molecularly imprinted nanoparticles for water-soluble pefloxacin mesylate prepared via surface initiated atom transfer radical polymerization and its application in egg sample analysis. AB - The novel superparamagnetic surface molecularly imprinted Fe3O4@MIP nanoparticles for water-soluble pefloxacin mesylate (PEF-M) were prepared via surface initiated atom transfer radical polymerization (si-ATRP). The binary mixture of methanol and water was selected as the polar solvents for fabricating PEF-M imprinted MIPs. The Fe3O4@MIP exhibited high saturation magnetization of 41.4 emu/g leading to the fast separation. The adsorption behaviors indicated that the Fe3O4@MIP nanoparticles possessed specific recognition and high affinity towards template PEF-M in aqueous media. Moreover, Fe3O4@MIP nanoparticles were directly used to selectively enrich PEF-M from egg samples. By RP-HPLC analysis, the recoveries of PEF-M were obtained as 92.8-96.5% with relative standard division of 2.4-4.0%. PMID- 22321952 TI - An application of new microwave absorption tube in non-polar solvent microwave assisted extraction of organophosphorus pesticides from fresh vegetable samples. AB - A new self-designed microwave absorption tube was used in microwave-assisted extraction of seven organophosphorus pesticides from four kinds of vegetable samples. The non-polar solvent was used as extraction solvent, and a new portable microwave extraction apparatus was used. By sealing graphite powder in glass tube, microwave absorption tube was made and used to heat samples directly. The extracts were directly analyzed by GC-MS without any clean-up process. The effects of some experimental parameters on extraction efficiency were investigated and optimized. 3.0 g of sample, 25 mL of hexane and three microwave absorption tubes were added in the microwave extraction vessel, the extraction was carried out under 425 W irradiation power at 70 degrees C for 8 min. The recoveries were in the range of 76.5-109.4% and the relative standard deviations were lower than 13.1%. PMID- 22321953 TI - Development of a carbon clad core-shell silica for high speed two-dimensional liquid chromatography. AB - We recently introduced a new method to deposit carbon on fully porous silicas (5 MUm) to address some of the shortcomings of carbon clad zirconia (C/ZrO(2)), which has rather low retention due to its low surface area (20-30 m(2)/g). The method enables the introduction of a thin, homogeneous layer of Al(III) on silica to serve as catalytic sites for carbon deposition without damaging the silica's native pore structure. Subsequent carbon deposition by chemical vapor deposition resulted in chromatographically useful carbon phases as shown by good efficiencies and higher retentivity relative to C/ZrO(2). Herein, we use the above method to develop a novel carbon phase on superficially porous silica (2.7 MUm). This small, new form of silica offers better mass transfer properties and higher efficiency with lower column back pressures as compared to sub 2 MUm silica packings, which should make it attractive for use as the second dimension in fast two-dimensional LC (LC * LC). After carbon deposition, several studies were conducted to compare the new packing with C/ZrO(2). Consistent with work on 5 MUm fully porous silica, the metal cladding did not cause pore blockage. Subsequent carbon deposition maintained the good mass transfer properties as shown by the effect of velocity on HETP. The new packing exhibits efficiencies up to ~5.6-fold higher than C/ZrO(2) for polar compounds. We observed similar chromatographic selectivity for all carbon phases tested. Consequently, the use of the new packing as the second dimension in fast LC*LC improved the peak capacity of fast LC * LC. The new material gave loading capacities similar to C/ZrO(2), which is rather as expected based on the surface areas of the two phases. PMID- 22321954 TI - Quantitative analysis of hydroperoxy-, keto- and hydroxy-dienes in refined vegetable oils. AB - Quantitative analysis of the main oxidation products of linoleic acid - hydroperoxy-, keto- and hydroxy-dienes - in refined oils is proposed in this study. The analytical approach consists of derivatization of TAGs into FAMEs and direct analysis by HPLC-UV. Two transmethylation methods run at room temperature were evaluated. The reactants were KOH in methanol in method 1 and sodium methoxide (NaOMe) in method 2. Method 1 was ruled out because resulted in losses of hydroperoxydienes as high as 90 wt%. Transmethylation with NaOMe resulted to be appropriate as derivatization procedure, although inevitably also gives rise to losses of hydroperoxydienes, which were lower than 10 wt%, and formation of keto- and hydroxy-dienes as a result. An amount of 0.6-2.1 wt% of hydroperoxydienes was transformed into keto- and hydroxy-dienes, being the formation of the former as much as three times higher. The method showed satisfactory sensitivity (quantification limits of 0.3 MUg/mL for hydroperoxy- and keto-dienes and 0.6 MUg/mL for hydroxydienes), precision (coefficients of variation <= 6% for hydroperoxydienes and <= 15% for keto- and hydroxy-dienes) and accuracy (recovery values of 85(+/- 4), 99(+/- 2) and 97.0(+/- 0.6) % for hydroperoxy-, keto- and hydroxy-dienes, respectively). The method was applied to samples of high-linoleic (HLSO), high-oleic (HOSO) and high-stearic high-oleic (HSHOSO) sunflower oils oxidized at 40 degrees C. Results showed that the higher the linoleic-to-oleic ratio, the higher were the levels of hydroperoxy-, keto- and hydroxy-dienes when tocopherols were completely depleted, i.e. at the end of the induction period (IP). Levels of 23.7, 2.7 and 1.1 mg/g oil were found for hydroperoxy-, keto- and hydroxy-dienes, respectively, in the HLSO when tocopherol was practically exhausted. It was estimated that hydroperoxydienes constituted approximately 100, 95 and 60% of total hydroperoxides in the HLSO, HOSO and HSHOSO, respectively, along the IP. PMID- 22321955 TI - Auditory extinction and spatio-temporal order judgment in patients with left- and right-hemisphere lesions. AB - Auditory extinction and spatio-temporal order judgment (STOJ) were assessed in patients with acquired brain damage by systematically manipulating onset times in bilateral stimulation under free-field conditions. We tested the hypothesis that extinction will be reduced by increasing stimulus onset asynchrony. Two groups of patients with right-hemisphere (RH, n=17) or left-hemisphere (LH, n=17) damage were investigated in comparison to a healthy control group (n=12). The patients were recruited based on previously diagnosed impairments: auditory discrimination deficits with (RH(E)/LH(E)) or without extinction (RH(0)/LH(0)) due to cortical and/or subcortical temporo-parietally centred lesions. Stimuli were presented bilaterally in the acoustic free-field, with an onset asynchrony of +/- 30 to +/- 150 ms, or unilaterally, from speakers located +/- 60 degrees . Low frequency (LF) and high frequency (HF) stimuli were used to address spatial auditory processing in the horizontal plane based on the two main cues of interaural time and interaural intensity differences, respectively. The subjects' task was to indicate whether they perceived one (left or right) or two stimuli (left and right), and in the case of two make an STOJ (left or right first). Temporal asynchrony significantly reduced extinction in those patients that previously exhibited extinction for bilateral-simultaneous stimulation (RH(E)/LH(E)). In addition, their error rates in STOJ were higher than the controls'. A number of patients with no previous signs of extinction in bilateral-simultaneous stimulation (RH(0)/LH(0)) also showed impaired STOJ: in RH(0) patients this was specific to ipsilesional-leading stimuli, whilst in LH(0) patients no side specific effect was observed. The data support the notion of differential roles for the two hemispheres in spatio-temporal auditory perception and are discussed with respect to prevalent models of extinction and its possible long-term reduction. PMID- 22321956 TI - Ambiguity's aftermath: how age differences in resolving lexical ambiguity affect subsequent comprehension. AB - When ambiguity resolution is difficult, younger adults recruit selection-related neural resources that older adults do not. To elucidate the nature of those resources and the consequences of their recruitment for subsequent comprehension, we embedded noun/verb homographs and matched unambiguous words in syntactically well-specified but semantically neutral sentences. Target words were followed by a prepositional phrase whose head noun was plausible for only one meaning of the homograph. Replicating past findings, younger but not older adults elicited sustained frontal negativity to homographs compared to unambiguous words. On the subsequent head nouns, younger adults showed plausibility effects in all conditions, attesting to successful meaning selection through suppression. In contrast, older adults showed smaller plausibility effects following ambiguous words and failed to show plausibility effects when the context picked out the homograph's non-dominant meaning (i.e., they did not suppress the contextually irrelevant dominant meaning). Meaning suppression processes, reflected in the frontal negativity, thus become less available with age, with consequences for subsequent comprehension. PMID- 22321957 TI - The relationship between physical activity and cognition in older Latinos. AB - OBJECTIVES: The purpose of this study was to explore the relationship between minutes spent participating in light and moderate/vigorous-intensity physical activity (PA) and cognition in older Latinos, controlling for demographics, chronic health problems, and acculturation. METHOD: A cross-sectional study design was used. Participants were self-identified Latinos, without disability, who had a score less than 14 on a 21-point Mini-Mental State Examination. Participants were recruited from predominantly Latino communities in Chicago at health fairs, senior centers, and community centers. PA was measured with an accelerometer, worn for 7 days. Episodic memory and executive function (inference control, inattention, and word fluency) were measured with validated cognitive tests. RESULTS: Participants were 174 Latino men (n = 46) and women (n = 128) aged 50-84 years (M = 66 years). After adjusting for control variables (demographics, chronic health problems) and other cognitive measures, regression analyses revealed that minutes per day of light-intensity PA (r = -.51), moderate/vigorous PA (r = -.56), and counts per minute (r=-.62) were negatively associated with lower word fluency. DISCUSSION: Findings suggest that the cognitive benefits of both light-intensity PA and moderate/vigorous PA may be domain-specific. PMID- 22321958 TI - A segmental monitoring strategy based on variable wavelength detection for quality control of three Polygonaceae herbs. AB - Radix Polygoni Multiflori, Rhizoma et Radix Polygoni Cuspidati, and Radix et Rhizoma Rhei are the most frequently used traditional Chinese medicines in the family Polygonaceae. The three herbal medicines (HMs) contain similar types of compounds. In Chinese Pharmacopoeia, five high-performance liquid chromatography (HPLC) coupled with ultraviolet (UV) detection methods have been employed for their quality control. The aim of this study was to develop a simple and conventional strategy, segmental monitoring based on variable wavelength detection (VWD), for simultaneous quantification of phenolic acids, flavonoids, stilbenes and anthraquinones in the three chemically analogous HMs. Compared with the commonly used HPLC-diode array detection (DAD), the proposed method afforded desirable performance on linearity, precision and sensitivity. Additionally, a quadrupole time-of-flight mass spectrometry (QTOF-MS) was applied to the structural confirmation of analytes from complex matrices. Based on the chemical profiles and contents of the analyses, 27 samples from three HMs were well classified using the principal component analysis. The results of this study demonstrated the potential and applicability of segmental monitoring strategy based on VWD for comprehensive quality control of HMs. PMID- 22321959 TI - Accessory muscle activation during the superimposed burst technique. AB - Quadriceps muscle activation is assessed using the superimposed burst technique. This technique involves percutaneous muscle stimulation superimposed during maximal isometric volitional knee extension. It is unknown whether accessory muscle activation during maximal knee extension influences estimates of quadriceps muscle activation. Our aim was to compare accessory muscle activation while performing the superimposed burst technique using investigator delivered verbal instruction to constrain the system (CS) and a participant preferred (PP) technique. Twenty five healthy, active individuals (13M/12F, age=23.8 +/- 3.35, height=72.73 +/- 14.51 cm, and weight=175.29 +/- 9.59 kg) were recruited for this study. All participants performed superimposed burst testing with (CS) and without (PP) verbal instruction to encourage isolated quadriceps activation during maximal isometric knee extension. The main outcome variables measured were knee extension torque, quadriceps central activation ratio and mean EMG of vastus lateralis, biceps femoris, and lumbar paraspinal muscles. There were significant differences in knee extension torque (CS=2.87 +/- 0.93 Nm/kg, PP=3.40 +/- 1.12 Nm/kg, p<0.001), superimposed burst torque (CS=3.40 +/-0.98 Nm/kg, PP=3.75 +/- 1.11 Nm/kg, p=0.002) and quadriceps CAR (CS=84.1 +/- 12.0%, PP=90.2 +/- 9.9%, p<0.001) between the techniques. There was also a significant difference in lumbar paraspinal EMG (CS=6.40 +/- 8.52%, PP=11.86 +/- 14.89%, p=0.043) between the techniques however vastus lateralis EMG was not significantly different. Patient instruction via verbal instruction to constrain proximal structures may help patient minimize confounders to knee extension torque generation while maximizing quadriceps activation. PMID- 22321960 TI - Diagnosis of testicular torsion by measuring attenuation of dual wavelengths in transmission geometry across the testis: an experimental study in a rat model. AB - OBJECTIVE: To develop a noninvasive and real-time dual-wavelengths optic system to detect testicular torsion in an animal model. Diagnosis of testicular torsion is challenging in emergency conditions and frequently ends with surgical exploration. MATERIALS AND METHODS: In this study, 9 male 8-month-old Wistar albino rats weighing an average of 400 g were used. A transverse incision on the upper scrotum was done and the right testis was torsed with a 720 degrees medial rotation. The other testis of each rat was used as the control or sham group. In the sham group, the testicle was moved out of the body but no torsion was applied before repositioning into the scrotum. Transmission of continuous-wave light through all testes at wavelengths of 660 nm and 940 nm were measured. RESULTS: The ratio of the average intensities of the transmitted light of both wavelengths -660 nm to 940 nm--was used as a parameter to diagnose testis torsion. The ratios were significantly different (P = .001) between the torsion group and control group. CONCLUSION: Our noninvasive technique measuring attenuation of dual wavelengths in transmission geometry across the testis has the ability to distinguish between the testis with and without torsion on the basis of a threshold value of the ratio. PMID- 22321961 TI - The time course of flow-mediated vasodilation and endothelial dysfunction in patients with a cardiovascular risk factor. AB - The relationship between having a cardiovascular risk factor and endothelial dysfunction observed on a time-course analysis of brachial artery flow-mediated vasodilation (FMD) remains unclear. We enrolled 257 patients who had at least one cardiovascular risk factor. We measured FMD magnitude of the percentage change in peak diameter (DeltaFMD), maximum FMD rate calculated as the maximum slope of dilation (FMD-MDR), and integrated FMD response calculated as the area under the dilation curve during the 60- and 120-second dilation periods (FMD-AUC60 and FMD AUC120) using a semiautomatic edge-detection algorithm. FMD-AUC60 and FMD-AUC120 were negatively correlated with the Framingham risk score (FMD-AUC60: r = -0.15, P = .023; FMD-AUC120: r = -0.17, P = .007), whereas this association was not found in the case of either the DeltaFMD or the FMR-MDR. The Framingham risk score was significantly higher in patients in the lowest tertile for FMD-AUC120 (FMD-AUC120 <5.0 mm * second) than in those in the highest tertile for FMD-AUC120 (FMD-AUC120 >=11.0 mm * second) (12.9 +/- 8.7 vs. 8.6 +/- 7.8%, P = .002). The lowest tertile for FMD-AUC120 was independently associated with the Framingham risk score (beta = 0.10, P = .011), after adjustments were made for age, gender, and smoking and drinking status. FMD-AUC120 was associated with cardiovascular risk. PMID- 22321962 TI - Cellular biomarkers of endothelial health: microparticles, endothelial progenitor cells, and circulating endothelial cells. AB - Endothelial dysfunction, the shift from a healthy endothelium to a damaged pro coagulative, pro-inflammatory, and pro-vasoconstrictive phenotype, is an early event in many chronic diseases that frequently precedes cardiovascular complications. Functional assessment of the endothelium can identify endothelial damage and predict cardiovascular risk; however, this assessment provides little information as to the mechanisms underlying development of endothelial dysfunction. Changes in plasma asymmetric dimethyl arginine levels, markers of lipid peroxidation, circulating levels of inflammatory mediators, indices of coagulation and cellular surrogates such as microparticles, circulating endothelial cells, and endothelial progenitor cells may reflect alterations in endothelial status and as such have been defined as "biomarkers" of endothelial function. Biomarkers may be chemical or cellular. This review examines some markers of endothelial dysfunction, with a particular focus on cellular biomarkers of endothelial dysfunction and their diagnostic potential. PMID- 22321963 TI - Comparison of the effects of aliskiren/valsartan in combination versus valsartan alone in patients with stage 2 hypertension. AB - The extent to which the combination of a renin inhibitor with an angiotensin receptor blocker (ARB) lowers clinic and ambulatory blood pressure (BP) versus an ARB alone in stage 2 hypertension is not well known. Hence, we performed an 8 week, randomized, double-blind study in 451 patients with stage 2 hypertension to compare the efficacy of the combination of aliskiren/valsartan 300/320 mg versus valsartan 320 mg. The primary endpoint was change in seated systolic BP from baseline to week 8 analyzed on the intent-to-treat (ITT) population using the last-observation-carried-forward (LOCF) approach; patients completing the entire treatment period (per-protocol completers) were similarly analyzed. For the predefined primary analysis, systolic BP reductions for aliskiren/valsartan (n = 230) and valsartan (n = 217) were -22.1 and -20.5 mm Hg, respectively (P = .295). In per-protocol completers, aliskiren/valsartan (n = 201) lowered BP significantly greater than valsartan (n = 196); -23.7 mm Hg versus -20.3 mm Hg, respectively (P = .028). Although limited by a small sample size (n = 76) using ambulatory BP monitoring, aliskiren/valsartan lowered the 24-hour BP significantly more than valsartan alone (-14.6/-9.0 mm Hg versus -5.9/-4.2 mm Hg; P < .01). Safety and tolerability were similar for the two treatment groups. These data demonstrate the importance of multiple modalities to assess BP changes in clinical trials of antihypertensive therapies, particularly in stage 2 hypertension. PMID- 22321964 TI - Assessing knowledge, attitude, and practice of emergency contraception: a cross- sectional study among Ethiopian undergraduate female students. AB - BACKGROUND: Emergency contraception (EC) is a type of modern contraception which is indicated after unprotected sexual intercourse when regular contraception is not in use. The importance of EC is evident in preventing unintended pregnancies and its ill consequences like unintended child delivery or unsafe abortion, which are the most common causes of maternal mortality. Therefore, EC need to be available and used appropriately as a backup in case regular contraception is not used, misused or failed. Knowing that Ethiopia is one of the countries with highest maternal mortality rate, this study aimed to assess the knowledge, attitude and practice of EC, and to further elucidate the relationship between these factors and some socioeconomic and demographic characteristics among female undergraduate students of Addis Ababa University (AAU). This information will contribute substantially to interventions intended to combat maternal mortality. METHODS: A Cross-sectional quantitative study among 368 AAU undergraduate students was conducted using self-administered questionnaire. Study participants were selected by stratified random sampling. Data was entered and analyzed using SPSS Version 17. Results were presented using descriptive statistics, cross tabulation and logistic regression. RESULTS: Among the total participants (n = 368), only 23.4% were sexually active. Majority (84.2%) had heard of EC; 32.3% had a positive attitude towards it. The main source of information reported by the respondents was Media (69.3%). Among those who were sexually active, about 42% had unprotected sexual intercourse. Among those who had unprotected sexual intercourse, 75% had ever used EC. Sexually active participants had significantly better attitude towards EC than sexually inactive participants (crude OR 0.33(0.15-0.71)); even after adjusting for possible confounders such as age, region, religion, ethnicity, marital status, department and family education and income (adj. OR 0.36(0.15-0.86)). CONCLUSIONS: The study showed high EC awareness and usage in contrast to other studies in the city, which could be due to the fact that university students are relatively in a better educational level. Therefore, it is highly recommended that interventions intended to combat maternal mortality through contraceptive usage need to be aware of such information specific to the target groups. PMID- 22321965 TI - Trigeminal satellite cells modulate neuronal responses to triptans: relevance for migraine therapy. AB - In the present paper, we have further developed an in vitro model to study neuronal-glial interaction at trigeminal level by characterizing the effects of conditioned medium (CM) collected from activated primary cultures of satellite glial cells (SGCs) on calcitonin gene-related peptide (CGRP) release from rat trigeminal neurons. Moreover, we investigated whether such release is inhibited by a clinically relevant anti-migraine drug, sumatriptan. CM effects were tested on trigeminal neuronal cultures in different conditions of activation and at different time points. Long-term exposures of trigeminal neurons to CM increased directly neuronal CGRP release, which was further enhanced by the exposure to capsaicin. In this framework, the anti-migraine drug sumatriptan was able to inhibit the evoked CGRP release from naive trigeminal neuron cultures, as well as from trigeminal cultures pre-exposed for 30 min to CM. On the contrary, sumatriptan failed to inhibit evoked CGRP release from trigeminal neurons after prolonged (4 and 8 h) pre-exposures to CM. These findings were confirmed in co culture experiments (neurons and SGCs), where activation of SGCs or a bradykinin priming were used. Our data demonstrate that SGCs activation could influence neuronal excitability, and that this event affects the neuronal responses to triptans. PMID- 22321966 TI - Tubal ectopic pregnancy. AB - INTRODUCTION: Approximately 1/100 pregnancies are ectopic, with the conceptus usually implanting in the fallopian tube. Some ectopic pregnancies resolve spontaneously, but others continue to grow and lead to rupture of the tube. Risks are higher in women with damage to the fallopian tubes due to pelvic infections, surgery, or previous ectopic pregnancy. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What treatments improve outcomes in women with unruptured tubal ectopic pregnancy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2011 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations, such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). The authors also separately searched Medline and Pubmed up to July 2011 in addition to the Clinical Evidence systematic search to support the comments and clinical guide sections. RESULTS: We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: salpingotomy, salpingectomy, methotrexate, methotrexate following salpingotomy, methotrexate plus mifepristone, and expectant management. PMID- 22321967 TI - Multiple sclerosis. AB - INTRODUCTION: Multiple sclerosis is the most common cause of neurological disability in young adults. Irreversible disability can occur, but life expectancy is generally not affected. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions aimed at reducing relapse rates and disability in people with multiple sclerosis? What are the effects of interventions to improve symptoms during acute relapse? What are the effects of treatments for fatigue, spasticity, and multidisciplinary care on disability in people with multiple sclerosis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2011 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 71 systematic reviews, RCTs, and observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review, we present information relating to the effectiveness and safety of the following key interventions: amantadine, azathioprine, behaviour modification, botulinum toxin, corticosteroids, exercise, gabapentin, inpatient or outpatient rehabilitation, interferon beta, intrathecal baclofen, intravenous immunoglobulin, methotrexate, mitoxantrone, modafinil, natalizumab, oral drug treatments, parenteral glatiramer acetate, physiotherapy, and plasma exchange. PMID- 22321968 TI - Impact of age on recurrence and severity of left colonic diverticulitis. AB - AIM: There has been controversy about the presentation and treatment of acute colonic diverticulitis (AD) in young patients. The aim of this observational study was to evaluate the virulence and natural history of AD in three different age groups of patients. METHOD: The study was performed on 686 patients with the diagnosis of a first episode of AD admitted between January 1998 and December 2008. Patients were classified into three groups: age 45 years or younger (group 1), 45-70 years of age (group 2) and 70 years or more (group 3). The variables studied were gender, American Society of Anesthesiologists status, associated comorbidity, type of treatment, length of hospital stay and recurrence of AD. RESULTS: Group 1 included 99 (14.4%) patients, group 2 339 (49.4%) and group 3 248 (36.2%). Of these, 144 patients needed emergency operation at the first admission, 25 underwent elective surgery after the first episode of AD and 10 died after medical treatment; 507 patients were followed for recurrence. In all, 104 (20.5%) patients had a recurrence of AD that required hospitalization. Fifty (9.9%) presented with one episode of severe recurrence, without any difference between the groups (P = 0.533). There were no differences in the analysis of cumulative recurrence (Kaplan-Maier) between the three groups. CONCLUSION: AD does not present a more aggressive clinical course in younger patients and it can be safely managed using the same strategy as in middle aged and older patients. PMID- 22321969 TI - Improved multislice calculations for including higher-order Laue zones effects. AB - A new method for including higher-order Laue zones (HOLZs) effects in an efficient way in electron scattering simulations has been developed and tested by detail calculations. The calculated results by the conventional multislice (CMS) method and the improved conventional multislice (ICMS) method using a large dynamical aperture to avoid numerical errors are compared with accurate results. We have found that the zero-order Laue zones (ZOLZs) reflection cannot be properly described only using the projected potential in the whole unit cell; in general, we need to subslice the electrostatic potential inside the unit cell. It is shown that the ICMS method has higher accuracy than the CMS method for the calculation of the ZOLZ, HOLZ and Pseudo-HOLZ reflections. Hence, ICMS method allows to use a larger slice thickness than the CMS method and reduces the calculation time. PMID- 22321970 TI - APC/C-Cdh1-dependent anaphase and telophase progression during mitotic slippage. AB - BACKGROUND: The spindle assembly checkpoint (SAC) inhibits anaphase progression in the presence of insufficient kinetochore-microtubule attachments, but cells can eventually override mitotic arrest by a process known as mitotic slippage or adaptation. This is a problem for cancer chemotherapy using microtubule poisons. RESULTS: Here we describe mitotic slippage in yeast bub2Delta mutant cells that are defective in the repression of precocious telophase onset (mitotic exit). Precocious activation of anaphase promoting complex/cyclosome (APC/C)-Cdh1 caused mitotic slippage in the presence of nocodazole, while the SAC was still active. APC/C-Cdh1, but not APC/C-Cdc20, triggered anaphase progression (securin degradation, separase-mediated cohesin cleavage, sister-chromatid separation and chromosome missegregation), in addition to telophase onset (mitotic exit), during mitotic slippage. This demonstrates that an inhibitory system not only of APC/C Cdc20 but also of APC/C-Cdh1 is critical for accurate chromosome segregation in the presence of insufficient kinetochore-microtubule attachments. CONCLUSIONS: The sequential activation of APC/C-Cdc20 to APC/C-Cdh1 during mitosis is central to accurate mitosis. Precocious activation of APC/C-Cdh1 in metaphase (pre anaphase) causes mitotic slippage in SAC-activated cells. For the prevention of mitotic slippage, concomitant inhibition of APC/C-Cdh1 may be effective for tumor therapy with mitotic spindle poisons in humans. PMID- 22321972 TI - [Advances in the treatment of atrial fibrillation]. PMID- 22321973 TI - [Renal artery stenosis complicated with heart failure: a perplexing combination]. PMID- 22321971 TI - The growth response to androgen receptor signaling in ERalpha-negative human breast cells is dependent on p21 and mediated by MAPK activation. AB - INTRODUCTION: Although a high frequency of androgen receptor (AR) expression in human breast cancers has been described, exploiting this knowledge for therapy has been challenging. This is in part because androgens can either inhibit or stimulate cell proliferation in pre-clinical models of breast cancer. In addition, many breast cancers co-express other steroid hormone receptors that can affect AR signaling, further obfuscating the effects of androgens on breast cancer cells. METHODS: To create better-defined models of AR signaling in human breast epithelial cells, we took estrogen receptor (ER)-alpha-negative and progesterone receptor (PR)-negative human breast epithelial cell lines, both cancerous and non-cancerous, and engineered them to express AR, thus allowing the unambiguous study of AR signaling. We cloned a full-length cDNA of human AR, and expressed this transgene in MCF-10A non-tumorigenic human breast epithelial cells and MDA-MB-231 human breast-cancer cells. We characterized the responses to AR ligand binding using various assays, and used isogenic MCF-10A p21 knock-out cell lines expressing AR to demonstrate the requirement for p21 in mediating the proliferative responses to AR signaling in human breast epithelial cells. RESULTS: We found that hyperactivation of the mitogen-activated protein kinase (MAPK) pathway from both AR and epidermal growth factor receptor (EGFR) signaling resulted in a growth-inhibitory response, whereas MAPK signaling from either AR or EGFR activation resulted in cellular proliferation. Additionally, p21 gene knock-out studies confirmed that AR signaling/activation of the MAPK pathway is dependent on p21. CONCLUSIONS: These studies present a new model for the analysis of AR signaling in human breast epithelial cells lacking ERalpha/PR expression, providing an experimental system without the potential confounding effects of ERalpha/PR crosstalk. Using this system, we provide a mechanistic explanation for previous observations ascribing a dual role for AR signaling in human breast cancer cells. As previous reports have shown that approximately 40% of breast cancers can lack p21 expression, our data also identify potential new caveats for exploiting AR as a target for breast cancer therapy. PMID- 22321974 TI - [Paying great attention to autopsy at Chinese major hospitals]. PMID- 22321975 TI - [Prevalence and prognostic value of liver function abnormalities in patients with chronic systolic heart failure]. AB - OBJECTIVE: To evaluate systemically the prevalence and prognostic values of liver function abnormalities in patients with chronic systolic heart failure (HF) have not been systematically evaluated. METHODS: A total of 16 681 hospitalized patients with a diagnosis of chronic systolic HF and left ventricular ejection fraction (LVEF) < 50% were recruited from 12 hospitals in Hubei Province. All patients were followed up by telephone contacts. And they were divided into the death and survival groups according to the follow-up results. RESULTS: Over a median follow-up period of 3 years, 6453 (38.69%) patients died. The prevalence of liver function abnormality was 71.94% (12 001/16 681). The elevations of direct bilirubin, gamma-glutamyl-transferase and alanine aminotransferase were the most common findings accounting for 33.37% (4863/14 574), 32.51% (4337/13 341) and 30.12% (5024/16 681) respectively. The abnormality of alkaline phosphatase was rare and its increase and decrease accounted for 3.82% (474/12 397) and 4.51% (559/12 397) respectively. The prevalence of low albumin and total bilirubin elevation was 23.24% (3408/14 664) and 19.37% (3231/16 681). And high direct bilirubin (HR 1.264, 95%CI 1.103 - 1.423; P = 0.02), high total bilirubin (HR 1.126, 95%CI 1.019 - 1.234; P = 0.02) and low albumin (HR 0.889, 95%CI 0.794 0.889; P < 0.01) were determined as the independent risk factors of total mortality. There were the correlations of LVEF with direct bilirubin (r = -0.235, P < 0.01), total bilirubin (r = -0.209, P < 0.01), albumin (r = 0.107, P < 0.01) and right ventricular end-diastolic diameter (RVDD) with direct bilirubin (r = 0.149, P < 0.01), total bilirubin (r = 0.154, P < 0.01) and albumin (r = -0.086, P < 0.01). CONCLUSION: The prevalence of liver function abnormalities is high in patients with chronic systolic HF. Low albumin, high direct bilirubin and high total bilirubin increase their total mortalities. Low LVEF and high RVDD are positively correlated with a high prevalence of liver function abnormalities. PMID- 22321976 TI - [Effects of aerobic exercise on exercise tolerance in patients with chronic heart failure]. AB - OBJECTIVE: To explore the effects of aerobic exercise on exercise tolerance in patients with chronic heart failure (CHF). METHODS: A total of 50 CHF patients with left ventricular ejection fraction (LVEF) < 49% by echocardiography were enrolled. And they were randomly divided into exercise group (n = 25) and non exercise group (n = 25). Cardiopulmonary exercise testing (CPET) was performed. The patients of exercise group underwent an aerobic exercise program in which exercise intensity was decided by anaerobic threshold (AT) before 10 J/s while those of non-exercise group performed daily activities. After 6 sessions of supervised aerobic exercise, the home-based aerobic exercise training began. CPET was re-examined 3 months later. RESULTS: The VO(2) AT, VO(2) peak, Load AT, Load peak, peak VO(2)/HR and VE/VCO(2) slope at baseline were similar between exercise group and non-exercise group (P > 0.05). The VO(2) AT, VO(2) peak, Load AT, Load peak and peak VO(2)/HR in patients of exercise group were increased compared with baseline, The differences between baseline and 3 months later expressed as DeltaVO(2) AT, DeltaVO(2) peak, DeltaLoad AT, DeltaLoad peak, Deltapeak VO(2)/HR and DeltaVE/VCO(2) slope, The differences of DeltaVO(2) AT, DeltaVO(2) peak, DeltaLoad AT, DeltaLoad peak and Deltapeak VO(2)/HR between two groups were statistically significant [DeltaVO(2) AT: 2.8 (1.2 - 3.5) ml*kg(-1)*min(-1) vs 0.3 (-2.8 - 0.1) ml*kg(-1)*min(-1), P < 0.01; DeltaVO(2) peak: 3.4 (1.8 - 4.6) ml*kg(-1)*min(-1) vs -0.5 (-1.4 - 0.3) ml*kg(-1)*min(-1), P < 0.01; DeltaLoad AT:15.0 (2.5 - 22.5) J/s vs 0.5(-4.2 - 3.8) J/s, P < 0.01; DeltaLoad peak: 15.0 (1.3 - 25.0) J/s vs 0.0 (-8.8 - 15.0) J/s, P < 0.05; Deltapeak VO(2)/HR: 2.3 (0.0 - 4.0) ml*kg(-1)*beat(-1) vs -0.1 (-0.7 - 1.2) ml*kg(-1)*beat(-1), P < 0.01]. The difference of DeltaVE/VCO(2) slope was not statistically significant [-2.3 (-12.2 - 1.8) vs 1.0 (-0.4 - 2.6), P > 0.05]. CONCLUSION: After 3 months of aerobic exercise, exercise capacity may improve in the CHF patients. PMID- 22321977 TI - [Influencing factors for the plasma concentration of N-terminal brain natriuretic peptide precursor in patients with heart failure due to various heart diseases]. AB - OBJECTIVE: To compare the plasma concentrations of N-terminal brain natriuretic peptide precursor (NT-proBNP) in patients with heart failure due to various heart diseases and analyze the influencing factors. METHODS: We enrolled a total of 804 heart failure patients due to various heart diseases, including valvular heart disease (VHD), dilated cardiomyopathy (DCM), ischemic heart diseases (IHD), restrictive cardiomyopathy (RCM), hypertensive heart disease (HHD), hypertrophic cardiomyopathy (HCM), pulmonary heart disease (PHD) and adult congenital heart disease (CHD). The plasma concentration of NT-proBNP was measured by enzyme linked immunosorbent assay (ELISA). Multiple linear regression analysis was used to detect the influencing factors for the plasma concentration of NT-proBNP. RESULTS: The plasma concentration of NT-proBNP had no significant difference between patients with VHD, DCM, IHD, RCM, HCM, PHD, HHD and CHD. The median (25 percent, 75 percent) values were 1866 (803 - 3973), 2247 (1087 - 3865), 2400 (1182 - 4242), 2456 (1385 - 5839), 2204 (1053 - 3186), 2285 (1155 - 3424), 2313 (655 - 3850) and 2768 (795 - 4371) pmol/L respectively (P > 0.05). It increased with New York Heart Association (NYHA) class from II through III to IV. The median (25 percent, 75 percent) values were 646 (447 - 1015), 2160 (1118 - 3750) and 3342 (1549 - 5455) pmol/L respectively (P < 0.01). The patients with a body mass index (BMI) of >= 25 kg/cm(2) had a lower NT-proBNP concentration than those with a BMI of < 25 kg/cm(2). The median (25 percent, 75 percent) values were 1468 (784 - 3177) and 2424 (1090 - 4213) pmol/L respectively (P < 0.01). Patients with a serum creatinine concentration of >= 107 umol/L had a higher NT-proBNP concentration than those < 107 umol/L. The median (25 percent, 75 percent) values were 3337 (1470 - 5380) and 1644 (781 - 3375) pmol/L respectively (P < 0.01). Multiple linear regression analysis demonstrated that NYHA class, creatinine, BMI, hepatic damage and diastolic pressure were independently associated with the plasma concentration of NT-proBNP (all P < 0.01). CONCLUSION: The plasma concentration of NT-proBNP has no significant difference between heart failure patients due to various heart diseases. Its level may be affected by NYHA class, serum creatinine, BMI, hepatic damage and diastolic pressure. PMID- 22321978 TI - [Retrospective analysis of related factors for patients with weaning difficulties in medical intensive care unit]. AB - OBJECTIVE: To explore the related factors of difficult-to-wean patients in medical intensive care unit (MICU). METHODS: A retrospective analysis was performed for 112 patients placed on mechanical ventilation. There were 63 males and 49 females with a mean age of (58 +/- 26) years. Their primary diseases included acute exacerbation of chronic obstructive pulmonary disease (AECOPD) (n = 27), pneumonia (n = 20), asthma (n = 12) and neuromuscular diseases (n = 8). Basic admission profiles, underlying diseases, accompanying diseases and pre weaning changes in physiological indicators were recorded. They were divided into 2 groups: successfully-weaned group and different-to-wean group. Logistic regression analysis was used to analyze the risk factors correlated with the difficult withdrawal of mechanical ventilation. RESULTS: There were 27 (24.1%) difficult-to-wean patients on mechanical ventilation in MICU. Some underlying diseases had statistical significance in both groups, including AECOPD (chi(2) = 6.238, P = 0.028), idiopathic pulmonary fibrosis (chi(2) = 5.232, P = 0.025) and neuromuscular disease (chi(2) = 14.635, P = 0.007). The ratios of difficult-to wean patients were 9/27, 2/6 and 6/8 respectively. There was statistical significance of pre-admission and pre-weaning oxygenation index between two groups (t = 2.183, 2.162, P < 0.05). Zubrod score at pre-weaning was also significantly different between two groups (t = 9.037, P < 0.05). Logistic regression indicated that the patients with severe heart failure (OR = 5.781), psychological disorders (OR = 4.654), obstructive sleep apnea (OR = 4.012), AECOPD (OR = 3.617) and neuromuscular diseases (OR = 2.885) were more vulnerable to weaning difficulties. CONCLUSION: The major risk factors of difficult-to-wean patients in MICU include severe heart failure, psychological diseases, obstructive sleep apnea, neuromuscular disease and AECOPD. And oxygenation and self-care capability may also affect weaning significantly. PMID- 22321979 TI - [Detecting minimal residual disease status in allogeneic hematopoietic stem cell transplantation of patients with high-risk acute leukemia]. AB - OBJECTIVE: To explore the relationship between minimal residual disease (MRD) and the outcome of patients with high-risk acute leukemia (AL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: By 4/5-color multi parameter flow cytometry (MFC, CD45/SSC gating) for detecting MRD at pre-(day-30) and post-transplant (day +30, +60, +100, 6 months, 9 months and 12 months), the investigators retrospectively analyzed the MRD levels and the prognosis of 90 high-risk patients. According to the MRD cutoff value of 0.1%, the low-level and high-level groups were defined. In the high-level group, the patients were divided into two sub groups according to the subsequent treatment (intervention therapy group and non-intervention therapy group). RESULTS: MRD pre-transplant had no predictive value for the clinical outcome. The patients with high levels of MRD post-transplant (+60 d and +100 d) showed higher relapse rates than those of the low-level group. In addition, regarding MRD +100 d post-transplant, differences were significant among 3 groups (high-level MRD and intervention therapy group, high-level MRD and non-intervention therapy group and low-level MRD group) including 1-year relapse-free survival (RFS) (100% vs 60.87% vs 91.30%, P < 0.05) and 3-year RFS (85.71% vs 44.72% vs 68.48%, P < 0.05). The median time from first high level MRD detected to clinical relapse was 2.5 (1 - 26) months. In the high level MRD group (+100 d post-transplant), 7 of 30 patients received intervention therapy without relapse. However another 23 patients had no intervention treatment and 11 of them relapsed latter (P < 0.05). CONCLUSION: The MFC-based quantification of MRD post-transplant reveals important prognostic information in patients with high-risk AL. MRD check point at day +100 (cutoff: 0.1%) may discriminate different risk populations. Those patients with MRD levels >= 0.1% should receive early intervention at an early stage and a low tumor burden so as to reduce the relapse rate and boost survival. PMID- 22321980 TI - [Multi-slice spiral CT scan with lower dose for preoperative evaluation: living renal donor kidney morphology and the quantification of unilateral glomerular filtration rate]. AB - OBJECTIVE: To explore the feasibility of multi-slice spiral computed tomography (CT) with a lower dose as one-off examination for the preoperative morphology evaluation and the quantification of unilateral renal glomerular filtration rate of living renal donors. METHODS: A total of 36 living renal donors at our hospital from May 2008 to June 2009 were examined by 64-slice spiral CT and single photon emission computed tomography (SPECT). Living renal donors were examined with a plain scan and three-phase enhancement CT scan. Also there were two inserted dynamic scans, one after the injection of contrast agent and the other between cortex and parenchymal phases. Image reconstructions were performed to observe renal parenchyma, renal vessels and collecting system. Comparisons were made with intra-operative findings. And the known Patlak equation was used simultaneously. The glomerular filtration rate (GFR) in a single kidney was calculated on CT and SPECT respectively. The GFRs of two groups were analyzed to investigate the Pearson correlation and simple linear regression between them. RESULTS: Twenty of 36 renal living donor kidneys underwent the operation, variations of morphology detected by CT were all corresponded with the operation. The GFR values estimated from CT were (42.4 +/- 8.9) ml/min (left) and 43.2 +/- 8.4) ml/min (right). While GFR of SPECT 47.4 +/- 9.3) ml/min (left) and 48.2 +/- 8.5) ml/min (right). Linear trend was found between the GFRs of CT and SPECT. Pearson's product-moment correlation coefficient r = 0.753 (left) (P < 0.01), r = 0.709 (right) (P < 0.01). These values indicated that the GFR from CT was positively correlated with the GFR from SPECT. CONCLUSION: During the preoperative evaluation, multi-slice spiral CT may provide both anatomic information and the GFR of living renal donors. PMID- 22321981 TI - [Surgical strategies for tumors with invasion of thoracic and abdominal great vessels]. AB - OBJECTIVE: To summarize the vascular surgical strategies for chest and abdomen tumors with the invasion of great vessels. METHODS: The clinical data were collected for 67 patients undergoing surgical treatment for tumors with the invasion of thoracic and abdominal great vessels at our hospital from January 2001 to June 2009. Then a retrospective analysis was performed. Among this dataset, there were 31 cases with only vessel wall invasion and 20 cases with only intravascular tumor thrombus. In the meanwhile, both the invasion of vascular walls and the formation of tumor thrombus were located in 16 patients. RESULTS: Among 67 operated patients, various strategies were used, including surgical adhesion lysis (n = 15), vascular resection direct suture (n = 24), artificial blood vessel patch (n = 10), pericardial patch (n = 3), artificial vascular replacement or bypass (n = 15) and cavity thrombectomy (n = 36). Cavity thrombectomy was performed under cardiopulmonary bypass for 8 patents with tumor invasion of right atrium. Among them, 58 patients received radical tumor resection while palliative resection was performed for 9 patients with a rate of complete resection at 86.6%. There was no intraoperative mortality with the perioperative death of 8 cases. A follow-up study was successfully conducted for 52 patients. And 7 patients were lost to follow-up. The overall follow-up rate was 88.1%. By June 2009, the survival period of this group of patients was as follows: 18 cases (> 48 months), 29 cases (> 24 months), 38 cases (> 12 months), 50 cases (> 6 months) and 2 cases (<= 6 months). Among these patients, the major cause of mortality was tumor metastasis. The patients with kidney cancer showed the most favorable surgical outcomes. CONCLUSION: Managed by a variety of vascular surgical techniques, the patients with tumors involving major blood vessels may achieve an excellent success rate of tumor resection and a better postoperative quality-of-life. PMID- 22321982 TI - [Association between lower urinary tract symptoms and erectile dysfunction in males aged 50 years and above: results from a multicenter community-based cross sectional survey (BPC-BPH)]. AB - OBJECTIVE: To survey the incidence of lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in males aged >= 50 years and explore the correlation between LUTS and ED. METHODS: A cross-sectional study was performed at Beijing communities in 1644 males aged over 50 years. The International Index of Erectile Function-5 (IIEF-5) and International Prostate Symptom Score (IPSS) were recorded. Pearson's chi(2) test and Spearman correlation coefficients were used to analyze the results of IPSS, LUTS and their correlations with ED. RESULTS: The mean age was 64.5 years old (range: 50-93), the mean value of IPSS(9.9 +/- 8.2), the prevalence of mild, moderate and severe LUTS 49.2% (809/1644), 36.4% (599/1644) and 14.4% (236/1644) respectively. The mean value of IIEF was (9.4 +/- 8.6), the total incidence of ED 90.5% (1487/1644) and the incidence of ED of mild, moderate and severe LUTS 85.7% (694/809), 93.7% (561/599) and 97.9% (231/236) respectively. The total IIEF-5 score was found significantly correlated with the total IPSS score (r = -0.335, P < 0.01), the obstructive symptoms (r = 0.276, P < 0.01)and irritative symptoms (r = -0.326, P < 0.01). The severity of LUTS was correlated with the severity of ED (r = 0.304, P < 0.01). Correlations also existed between age and total IPSS score(r = 0.388, P < 0.01), LUTS severity (r = 0.457, P < 0.01), total IIEF score (r = -0.533, P < 0.01) or ED severity (r = 0.529, P < 0.01). CONCLUSION: The incidence of LUTS or ED in aging males increases with age. The severity of ED is positively correlated with the severity of LUTS. Irritative and obstructive symptoms influence the occurrence of ED in aging males. PMID- 22321983 TI - [Therapeutic feasibility of percutaneous puncture and chemical neurolysis of thoracic sympathetic nerve block in palmar hyperhidrosis under the guidance of computed tomograph]. AB - OBJECTIVE: To explore the therapeutic feasibility of percutaneous puncture and neurolytic thoracic sympathetic nerve block under the guidance of computed tomograph (CT). METHODS: From September 2009 to August 2010, 23 cases with primary palmar hyperhidrosis underwent percutaneous puncture and neurolytic thoracic sympathetic nerve block at our hospital. The puncture of thoracic sympathetic nerve was guided by CT through the gap of T3-4. The screen showed the direction of needle and the location of needle tip at the upper joint of costal head beside T3 body and outside of costal pleura. A mixed injection of 1% lidocaine and 30% iohexol was administered. On CT, lidocaine was found to cover the area where the thoracic sympathetic nerve was located. And after several minutes, the patient's palms turned warm and dry from cool and wet without the onset of Horner's syndrome. Then 2.5 ml of absolute alcohol was injected to block the thoracic sympathetic nerve. RESULTS: CT could guide the needle to the right position. And the injectate spreaded to the site of thoracic sympathetic nerve. At 5 min after anesthetic injection, the palmar temperature raised an average of 2.86 degrees C and the amplitude of pulse rose over 55%. Palmar hyperhidrosis was cured in 19 patients by one attempt and 4 patients required a second block with absolute alcohol. No complication occurred and there were 2 patients with tendency of recurrence during a follow-up period of 8 - 18 months. CONCLUSION: The CT-guided therapy of percutaneous puncture and chemical neurolysis of thoracic sympathetic nerve block is both feasible and efficacious for palmar hyperhidrosis. PMID- 22321984 TI - [Study of TGF-beta1 phage model peptides on inhibiting keloid fibroblasts proliferation]. AB - OBJECTIVE: To isolate the transforming growth factor-beta 1 (TGF-beta1) phage model peptides from phage 12-mer display peptide library to inhibit the proliferation of keloid fibroblasts. METHODS: The phage display 12-mer peptide library was screened for 4 rounds with monoclonal anti-human TGF-beta1 as the target to yield the specific phage model peptides. The 3-(4,5-dimethylthiazol-2 yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used for the quantitative determination of cellular proliferation. Apoptosis was detected by the Annexin V FITC/PI apoptosis detection kit and the cells were analyzed with flow cytometry. Immunofluorescent assay was employed to show the binding affinity of model peptides for keloid fibroblasts. Quantitative real-time polymerase chain reaction (PCR) was performed to detect the expressions of nuclear factor kappa B (NF kappaB) and connective tissue growth factor (CTGF). RESULTS: Ten phage model peptides were obtained and they were similar to TGF-beta1, TGF-beta2, TGF-beta receptor II (TbetaRII), TGF-beta-induced factor, NF-kappaB or mitogen-activated protein kinase (MAPK). The results of MTT showed that four phage model peptides (No. 7 - 10) could inhibit the proliferation of keloid fibroblasts (P < 0.05). The results of apoptotic assessment showed that phage model peptides (No. 7 - 10) could slightly trigger the late apoptotic stage of keloid fibroblasts. The data of immunofluorescence assay revealed that the model peptides on phages rather than phages could bind to keloid fibroblasts. The findings of quantitative real time PCR analysis suggested that the relative expression of NF-kappaB decreased in phage model peptides groups (No. 7 - 10). The quantitative expression was 0.28, 0.26, 0.46 and 0.30 respectively versus the negative control group. The relative expression of CTGF decreased in phage model peptides groups (No. 7 - 10). The quantitative expression was 0.26, 0.60, 0.34 and 0.17 respectively versus the negative control group. CONCLUSION: Four phage model peptides (No. 7 - 10) isolated from phage display 12-mer peptide library can inhibit the proliferation of keloid fibroblasts via regulating the expressions of NF-kappaB and CTGF. PMID- 22321985 TI - [Protective functions of recombinant protein targeted at RANKL against hepatic ischemia/reperfusion injury transfected by retrovirus in mice]. AB - OBJECTIVE: To explore the protective functions of recombinant protein RANK-Fc against hepatic ischemia/reperfusion injury and clarify its possible mechanism. METHODS: Sixty male Balb/c mice were randomly divided into 3 groups according to different treatments: serum-free medium control (Sham) group, target gene retrovirus (RANK-Fc) group and empty vector retrovirus (eGFP) group. All mice were injected with 2.5 ml solution (with or without retrovirus) within 6 seconds via tail vein. After 3 days, the model of 70% hepatic ischemia/reperfusion was induced under warm conditions for 90 minutes after different periods of reperfusion in RANK-Fc and eGFP groups; Sham group underwent the same procedure without the occlusion of blood supply. Blood and liver samples were obtained at different time points (1, 3, 6 and 24 h; n = 5 in each). Reverse transcription polymerase chain reaction (RT-PCR) was used for the evaluation of eGFP mRNA expression. RANK-Fc was assessed by Western blot. Liver transaminases and histopathological changes were used for the evaluation of hepatic injury. The activity of NF-kappaB in liver nucleus was analyzed by Western blot and immunohistochemistry. The activation level of JNK was also assessed by Western blot. Liver homogenate levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 were detected by enzyme-linked immunosorbent assay (ELISA). Apoptosis was identified by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis. The differences between three treatment groups at each time point were detected by the one-way ANOVA. Statistical analysis for inter-comparison was performed by Student's t test. RESULTS: RANK-Fc and eGFP were successfully expressed in liver after hydrodynamics-based transfection. Compared with eGFP group, RANK-Fc significantly improved liver functions at the same time point (P < 0.01), decreased NF-kappaB nuclear translocation (t = 6.726, P < 0.01)and JNK phosphorylation (t = 6.713, P < 0.01)and obviously suppressed the release of pro-inflammatory cytokine TNF-alpha (t = 4.779, P < 0.01) and IL-6 (t = 5.482, P < 0.01). Morphological injuries were markedly alleviated while the expressions of immunohistochemical positive cells and TUNEL staining positive cells decreased in RANF-Fc group. CONCLUSION: RANK-Fc has protective functions against hepatic ischemia/reperfusion injury in mice. Its mechanism is at least partially related with the suppressions of proinflammatory NF-kappaB and proapoptotic JNK signaling pathways. PMID- 22321986 TI - Abundance of birds in Fukushima as judged from Chernobyl. AB - The effects of radiation on abundance of common birds in Fukushima can be assessed from the effects of radiation in Chernobyl. Abundance of birds was negatively related to radiation, with a significant difference between Fukushima and Chernobyl. Analysis of 14 species common to the two areas revealed a negative effect of radiation on abundance, differing between areas and species. The relationship between abundance and radiation was more strongly negative in Fukushima than in Chernobyl for the same 14 species, demonstrating a negative consequence of radiation for birds immediately after the accident on 11 March 2011 during the main breeding season in March-July, when individuals work close to their maximum sustainable level. PMID- 22321987 TI - Recent advances in pathway-targeted cancer drug therapies emerging from cancer genome analysis. AB - Substantial recent progress has been reported in the context of implementing 'personalized' cancer medicine, informed by tumor genotyping. The recent FDA approvals of crizotinib, an ALK kinase inhibitor that has yielded significant clinical benefit in ALK-translocated lung cancers, and vemurafenib, a BRAF selective kinase inhibitor that has demonstrated dramatic clinical efficacy in BRAF mutant melanoma patients, define the new landscape for tailored cancer drug therapy. However, acquired drug resistance remains a significant obstacle to the long-term benefit of such treatments. Here, we review these and other recent developments that are paving the way for future efforts to optimize the clinical utility of pathway-targeted cancer drug therapies. PMID- 22321988 TI - Using genetically engineered mouse models to validate candidate cancer genes and test new therapeutic approaches. AB - Genetically engineered mouse models (GEMMs) have contributed greatly to the field of cancer research. In contrast to tumor cell transplantation models, GEMMs have the potential to capture both the cell-intrinsic and cell-extrinsic factors that drive de novo formation of autochthonous tumors and their progression toward metastatic disease. In addition, GEMMs provide experimentally tractable in vivo platforms for validating candidate cancer genes, determining therapy efficacy, and defining mechanisms of drug resistance. Studies in GEMMs of human cancer provide new insight in the molecular biology of cancer and contribute to development of novel therapeutic strategies that may ultimately lead to more cures rather than temporal remissions. PMID- 22321989 TI - Investigation of the physicochemical properties of CuO-CoO binary metal oxides supported on gamma-Al2O3 and their activity for NO removal by CO. AB - The dispersion and physicochemical behaviors of CuO-CoO binary metal oxides supported on gamma-Al(2)O(3) were characterized by XRD, LRS, XPS, H(2)-TPR, and in situ FT-IR techniques. Their activities were evaluated by NO-CO model reaction. The results indicated that (a) for lower loadings, CuO and CoO were able to be highly dispersed on the surface of gamma-Al(2)O(3) support; (b) the interaction between dispersed CuO and CoO upon gamma-Al(2)O(3) was discussed in the view of incorporation model. According to this model and obtained results, the surface dispersed Cu-O-Co species were considered to exist on the surface of gamma-Al(2)O(3); (c) CO or/and NO adsorption FT-IR results evidenced that the surface dispersed copper species could be reduced to lower valence by CO and the NO adsorption species converted with the increase in the temperature; (d) the surface dispersed Cu-O-Co species could be reduced to active Cu-?-Co species by CO among the mixture atmosphere. The formation of the surface synergetic oxygen vacancy (SSOV) was a crucial factor in the process of the NO-CO reaction. And a possible reaction pathway was tentatively proposed to discuss the NO-CO reaction based on all of these results. PMID- 22321990 TI - Structural transitions induced by shear flow and temperature variation in a nonionic surfactant/water system. AB - In this study, we investigate structural transitions of tetraethylene glycol monohexadecyl ether (C(16)E(4)) in D(2)O as a function of shear flow and temperature. Via a combination of rheology, rheo-small-angle neutron scattering and rheo-small-angle light scattering, we probe the structural evolution of the system with respect to shear and temperature. Multi-lamellar vesicles, planar lamellae, and a sponge phase were found to compete as a function of shear rate and temperature, with the sponge phase involving the formation of a new transient lamellar phase with a larger spacing, coexisting with the preceding lamellar phase within a narrow temperature-time range. The shear flow behavior of C(16)E(4) is also found to deviate from other nonionic surfactants with shorter alkyl chains (C(10)E(3) and C(12)E(4)), resembling to the C(16)E(7) case, of longer chain. PMID- 22321991 TI - Photocatalytic decolourisation of Reactive Red 4 dye by an immobilised TiO2/chitosan layer by layer system. AB - The synergistic photocatalysis-adsorption processes by the immobilized TiO(2)/chitosan layer by layer system on a glass support (TiO(2)/CS/glass) were investigated for the decolourisation of Reactive Red 4 (RR4) dye solution. Effects of different reaction parameters such as TiO(2) loading, initial pH of the solution, visible light, dissolved oxygen and radical quenchers were studied. The decolourisation rate of RR4 by TiO(2)/CS/glass was more than 32 times faster than a single layer of TiO(2) but was highly dependent on the TiO(2) loading and the initial pH of the solution. A thin layer of TiO(2) and acidic conditions favoured the adsorption of RR4 at the TiO(2)/CS interface. The h(+)/OH() species that diffused from the TiO(2) layer into the TiO(2)/CS interface oxidised the chemisorbed RR4 anions at the interface, and the generated electrons were then transferred to the conduction band of TiO(2). Excess electrons in the conduction band of TiO(2) increased the number of superoxide ions produced and thus improved the photocatalytic decolourisation of RR4. Therefore, apart from the synergistic photocatalysis-adsorption processes, a charge transfer process was also found to be responsible for maintaining the efficiency, sustainability and reusability of the TiO(2)/CS/glass layer by layer system. PMID- 22321992 TI - Novel hybrid molecules based on 15-membered azalide as potential antimalarial agents. AB - Malaria remains the most prevalent tropical disease, and due to the spread of resistant parasites novel therapeutics are urgently needed. Azithromycin has shown potential in malaria treatment so we designed hybrid azalide molecules with the aim to improve activity against and selectivity for the malaria parasite. Novel hybrid molecules comprising 4-aminoquinoline moiety covalently liked to 15 membered azalide scaffold at position C-3' were synthesized and biologically evaluated. Antimalarial testing against Plasmodium falciparum sensitive and resistant strains confirmed the improved in vitro activity over azithromycin and chloroquine. Selectivity of the compounds (HepG2 IC(50)/P. falciparum IC(50) ratio) for the parasite was high (100-2700) and their antibacterial activity diminished. Even though oral bioavailability determined for compound 12 was low, novel quinoline C-3'-substituted 15-membered azalides represent an interesting subclass of antimalarial macrolides that need further research and evaluation. PMID- 22321993 TI - Synthesis and antifungal activity of a new series of 2-(1H-imidazol-1-yl)-1 phenylethanol derivatives. AB - A new series of aromatic ester and carbamate derivatives of 2-(1H-imidazol-1-yl) 1-phenylethanol were synthesized and evaluated for their antifungal activity towards Candida albicans and non-albicans Candida species strains. The aromatic biphenyl ester derivatives 6a-c were more active than the reference compound fluconazole. 6c possesses a MIC mean values of 1.7 +/- 1.4 MUg mL(-1)vs C. albicans and 1.9 +/- 2.0 MUg mL(-1)vs non-albicans Candida species strains. The racemic mixtures of 6a, b were purified to afford the pure enantiomers. The (-) isomers were up to 500 times more active than (+) isomers. (-)-6a and (-)-6b were thirty and ninety times more active than fluconazole towards C. krusei strain respectively. The racemates of 6a-c showed low cytotoxicity against human monocytic cell line (U937) with 6a demonstrating a CC(50) greater than 128 MUg mL(-1). PMID- 22321994 TI - Novel metal based anti-tuberculosis agent: synthesis, characterization, catalytic and pharmacological activities of copper complexes. AB - Copper complexes of molecular formulae, [CuL(1)(OAc)], [CuL(2)(H(2)O)], [CuL(3)(H(2)O)], [CuL(4)(H(2)O)], [CuL(5)(H(2)O)] where L(1)-L(5) represents Schiff base ligands [by the condensation of 3-hydroxyflavone with 4 aminoantipyrine (L(1))/o-aminophenol (L(2))/o-aminobenzoic acid (L(3))/o aminothiazole (L(4))/thiosemicarbazide (L(5))], have been prepared. They were characterized using analytical and spectral techniques. The DNA binding properties of copper complexes were studied using electronic absorption spectra and viscosity measurements. Superoxide dismutase and antioxidant activities of the copper complexes have also been studied. Furthermore, the copper complexes have been found to promote pUC18 DNA cleavage in the presence of oxidant. Anti tuberculosis activity was also performed. PMID- 22321995 TI - Molecular diagnosis and detection of Pneumocystis jirovecii DHPS and DHFR genotypes in respiratory specimens from Colombian patients. AB - A total of 98 respiratory specimens from 88 patients suspected of having Pneumocystis jirovecii pneumonia (PcP) were evaluated using a previously reported nested polymerase chain reaction (PCR) assay for mitochondrial large subunit rRNA (mtLSUrRNA). In addition, samples from patients with other pulmonary infections and a sizeable DNA collection from other fungal pathogens were studied. A panfungal PCR assay amplifying the ITS1-ITS2 regions were also used to identify all fungal DNAs. All samples positive for mtLSUrRNA-PCR were evaluated to determine mutations in dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) genes. All PCR-amplified products were sequenced. Of the 98 clinical specimens, 13 (13.2%) were positive by GMS stain and mtLSUrRNA-PCR, while 32 (32.6%) that were GMS stain-negative gave positive results with mtLSUrRNA-PCR. All the sequences corresponding to the 45 products amplified by mtLSUrRNA-PCR showed 99% or greater identity with P. jirovecii. The mtLSUrRNA-PCR exhibited 86% sensitivity and 98% and 96.6% specificity when results were compared to those corresponding to negative controls and other proven clinical entities, respectively. We found mutations in the DHPS gene in 3 (7.7%) patients, 2 located at codon 55 and 1 at codon 57. One patient showed a synonymous substitution at nucleotide position 312 in the DHFR gene. These results suggest that mtLSUrRNA-PCR is a useful test for diagnosing PcP. In contrast to other studies, this study found a low prevalence of mutations in the DHPS and DHFR genes in Colombian patients. PMID- 22321996 TI - Human granulocytic anaplasmosis in eastern France: clinical presentation and laboratory diagnosis. AB - Human granulocytic anaplasmosis (HGA) is a tick-borne infection characterised by an acute, nonspecific febrile illness. To date, few clinical cases have been supported by both a positive polymerase chain reaction (PCR) assay and subsequent seroconversion against Anaplasma phagocytophilum antigen all over Europe. We report here 3 consecutive cases of HGA that occurred during the summer of 2009 which fulfilled the epidemiologic, clinical, and biological criteria for HGA. These data highlight PCR assay on ethylenediaminetetraacetic acid blood rather than serology as the diagnostic test of choice during the acute phase of the disease. In endemic areas, HGA should be investigated in patients presenting an undifferentiated febrile illness with cytopenia, elevated rates of liver enzymes, and increased C-reactive protein values. PMID- 22321997 TI - Development of real-time polymerase chain reaction assay for specific detection of Tsukamurella by targeting the 16S rRNA gene. AB - Recently, members of the genus Tsukamurella have been implicated as important etiologic pathogens contributing to bloodstream and pulmonary infections in immunocompromised patients. Tsukamurella species share many features with other mycolic acid-containing genera of the order Actinomycetales and might therefore be misidentified as belonging to one of these genera. We developed a TaqMan-based real-time polymerase chain reaction assay for the rapid and specific detection of infections due to Tsukamurella species. The assay amplifies and detects a 157-bp segment of the 16S rRNA gene of Tsukamurella. The specificity of the assay was confirmed using a panel of DNAs from 12 Tsukamurella strains and 11 strains belonging to 8 phylogenetic closely related genera. The sensitive and specific nature of the assay provides a valuable tool for the early and precise diagnosis of Tsukamurella infections in clinical diagnostic laboratories. PMID- 22321998 TI - Evaluation of quinolone resistance-determining region mutations and efflux pump expression in Neisseria meningitidis resistant to fluoroquinolones. AB - Three Neisseria meningitidis serotype B strains displaying elevated ciprofloxacin MIC values (0.06 and 0.25 MUg/mL) and a GyrA alteration at T91I have been described in the United States by Wu et al. [Wu et al., (2009) Emergence of ciprofloxacin-resistant Neisseria meningitidis in North America. N. Engl. J. Med. 360:886-892] and were further evaluated here by reference broth microdilution against fluoroquinolones (FQ) and other antimicrobial agents. Additional quinolone resistance-determining region (QRDR) mutations and alterations in structure and expression of the mtrCDE efflux system, including its intergenic regions, were also analyzed. Two strains showed ciprofloxacin and levofloxacin MIC values at 0.25 MUg/mL, and 1 strain had a ciprofloxacin MIC at 0.06 MUg/mL. In addition to T91I, the 2 strains displaying higher FQ MIC values also possessed a T173A alteration on GyrA. All components of the efflux pump mtrCDE (also associated with rifampin resistance) were intact, excluding the presence of insertions/deletions within the pump operon. The promoter region (mtrR) was fully sequenced and was distinct from FQ-susceptible controls. Isolates with higher ciprofloxacin MIC values had identical promoter region, whereas the isolate displaying a lower ciprofloxacin MIC value possessed a different sequence. Expression experiments showed discrepancies of the mRNA in pump components. The most remarkable difference was for the outer membrane protein encoded by mtrE that was hyperexpressed (>3600* elevated compared to control) in the strain displaying a ciprofloxacin MIC value of 0.06 MUg/mL. These results confirm that T91I alteration on GyrA had an important role in elevating ciprofloxacin MIC values; however, additional resistance determinants, including other gyrA mutations, also contribute to higher FQ MIC levels. Alterations in expression of mtrCED pump appear to have minimal influence on ciprofloxacin resistance, and this finding was supported by low rifampin susceptible-level results (MIC, <=0.008 to 0.03 MUg/mL). PMID- 22321999 TI - Update on antimicrobial susceptibility and genotype of Neisseria gonorrhoeae isolated in Italy. AB - Antimicrobial susceptibilities and genotypes of Neisseria gonorrhoeae collected in 2006-2010 from 6 medical centers located in Italy were compared with those from a previous survey conducted in 2003-2005. Resistance to ciprofloxacin increased from 34.2% to 62% whereas penicillin resistance declined from 25.5% to 14%. Important change in antimicrobial resistance rates and a high genetic variability among N. gonorrhoeae from Italy were observed. PMID- 22322000 TI - Comparison of BD Phoenix and bioMerieux Vitek 2 automated systems for the detection of macrolide-lincosamide-streptogramin B resistance among clinical isolates of Staphylococcus. AB - Two automated systems, BD Phoenix and bioMerieux Vitek 2, were compared to a double-disk diffusion method for the detection of inducible resistance to clindamycin in Staphylococcus spp. Analysis of 524 clinical isolates revealed sensitivity and specificity of 100% and 99.6%, respectively, for Phoenix and 91.1% and 99.8%, respectively, for Vitek 2. PMID- 22322001 TI - Effect of heterophoria type and myopia on accommodative and vergence responses during sustained near activity in children. AB - The influence of phoria-type and myopia on changes to vergence and accommodation during prolonged near-task was examined in 53 children. Participants were classified into phoria and refractive categories based on near phoria and cycloplegic refraction respectively. Measures of near phoria, binocular (BA) and monocular accommodation (MA) were obtained before and during a 20 min task when children binocularly fixated a high-contrast target at 33 cm through best corrective lenses. Vergence adaptation and accommodative adaptation were quantified using changes to near phoria and tonic accommodation respectively. The direction and magnitude of vergence adaptation was modified by the phoria-type (p<0.001). Emmetropic exophores displayed convergent (less exo than baseline) adaptation while esophores showed divergent shifts (less eso than baseline) in phoria upon prolonged fixation. Myopic children also followed a similar pattern but showed greater divergent (or less convergent) shift (p<0.001) in vergence adaptation for all phoria categories compared to emmetropes. Phoria-type also influenced the pattern of BA vs. MA (p<0.001) such that exophores showed BA>MA while esophores showed MA>BA in both refractive groups. Accommodative adaptation was higher in myopes (p=0.010) but did not demonstrate a significant effect of phoria (p=0.4). The influence of phoria-type on vergence adaptation and the pattern of BA vs. MA relates primarily to the varying fusional vergence demands created by the direction of phoria. The greater divergent (or less convergent) shift in vergence adaptation seen in myopes (compared to emmetropes) could be attributed to their higher accommodative adaptation. Nevertheless, the adaptive patterns observed in myopic children do not appear to explain their high response AV/A ratios identified as a risk factor for myopia development. PMID- 22322002 TI - Community specificity: life and afterlife effects of genes. AB - Community-level genetic specificity results when individual genotypes or populations of the same species support different communities. Our review of the literature shows that genetic specificity exhibits both life and afterlife effects; it is a widespread phenomenon occurring in diverse taxonomic groups, aquatic to terrestrial ecosystems, and species-poor to species-rich systems. Such specificity affects species interactions, evolution, ecosystem processes and leads to community feedbacks on the performance of the individuals expressing the traits. Thus, genetic specificity by communities appears to be fundamentally important, suggesting that specificity is a major driver of the biodiversity and stability of the world's ecosystems. PMID- 22322003 TI - Association mapping of plant resistance to insects. AB - Association mapping is rapidly becoming an important method to explore the genetic architecture of complex traits in plants and offers unique opportunities for studying resistance to insect herbivores. Recent studies indicate that there is a trade-off between resistance against generalist and specialist insects. Most studies, however, use a targeted approach that will easily miss important components of insect resistance. Genome-wide association mapping provides a comprehensive approach to explore the whole array of plant defense mechanisms in the context of the generalist-specialist paradigm. As association mapping involves the screening of large numbers of plant lines, specific and accurate high-throughput phenotyping (HTP) methods are needed. Here, we discuss the prospects of association mapping for insect resistance and HTP requirements. PMID- 22322005 TI - Direct interaction between HLA-B and carbamazepine activates T cells in patients with Stevens-Johnson syndrome. AB - BACKGROUND: Increasing studies have revealed that HLA alleles are the major genetic determinants of drug hypersensitivity; however, the underlying molecular mechanism remains unclear. OBJECTIVE: We adopted the HLA-B*1502 genetic predisposition to carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) as a model to study the pathologic role of HLA in delayed-type drug hypersensitivity. METHODS: We in vitro expanded CBZ specific cytotoxic T lymphocytes (CTLs) from patients with CBZ-induced SJS/TEN and analyzed the interaction between HLA-B and CBZ analogs based on CTL response, surface plasmon resonance, peptide-binding assay, site-directed mutagenesis, and computer modeling. RESULTS: The endogenous peptide-loaded HLA-B*1502 molecule presented CBZ to CTLs without the involvement of intracellular drug metabolism or antigen processing. The HLA-B*1502/peptide/beta(2)-microglobulin protein complex showed binding affinity toward chemicals sharing 5-carboxamide on the tricyclic ring, as with CBZ. However, modifications of the ring structure of CBZ altered HLA-B*1502 binding and CTL response. In addition to HLA-B*1502, other HLA-B75 family members could also present CBZ to activate CTLs, whereas members of the HLA-B62 and HLA-B72 families could not. Three residues (Asn63, Ile95, and Leu156) in the peptide-binding groove of HLA-B*1502 were involved in CBZ presentation and CTL activation. In particular, Asn63 shared by members of the B75 family was the key residue. Computer simulations revealed a preferred molecular conformation of the 5-carboxamide group of CBZ and the side chain of Arg62 on the B pocket of HLA B*1502. CONCLUSIONS: This study demonstrates a direct interaction of HLA with drugs, provides a detailed molecular mechanism of HLA-associated drug hypersensitivity, and has clinical correlations for CBZ-related drug-induced SJS/TEN. PMID- 22322004 TI - Filaggrin loss-of-function mutations are associated with enhanced expression of IL-1 cytokines in the stratum corneum of patients with atopic dermatitis and in a murine model of filaggrin deficiency. AB - BACKGROUND: Filaggrin (FLG) mutations result in reduced stratum corneum (SC) natural moisturizing factor (NMF) components and consequent increased SC pH. Because higher pH activates SC protease activity, we hypothesized an enhanced release of proinflammatory IL-1 cytokines from corneocytes in patients with atopic dermatitis (AD) with FLG mutations (AD(FLG)) compared with that seen in patients with AD without these mutations (AD(NON-FLG)). OBJECTIVES: We sought to investigate SC IL-1 cytokine profiles in the uninvolved skin of controls and patients with AD(FLG) versus patients with AD(NON-FLG). We also sought to examine the same profiles in a murine model of filaggrin deficiency (Flg(ft)/Flg(ft) [Flg(delAPfal)] mice). METHODS: One hundred thirty-seven patients were studied. NMF levels were ascertained using confocal Raman spectroscopy; transepidermal water loss and skin surface pH were measured. IL-1alpha, IL-1beta, IL-18, IL-1 receptor antagonist (IL-1RA), and IL-8 levels were determined in SC tape strips from 93 patients. All subjects were screened for 9 FLG mutations. Flg(ft)/Flg(ft) (Flg(delAPfal)) mice, separated from maFlg(ft)/maFlg(ft) (flaky tail) mice, were used for the preparation and culture of primary murine keratinocytes and as a source of murine skin. RT-PCR was performed using primers specific for murine IL 1alpha, IL-1beta, and IL-1RA. RESULTS: SC IL-1 levels were increased in patients with AD(FLG); these levels were inversely correlated with NMF levels. NMF values were also inversely correlated with skin surface pH. Skin and keratinocytes from Flg(ft)/Flg(ft) mice had upregulated expression of IL-1beta and IL-1RA mRNA. CONCLUSIONS: AD(FLG) is associated with an increased SC IL-1 cytokine profile; this profile is also seen in a murine homologue of filaggrin deficiency. These findings might have importance in understanding the influence of FLG mutations on the inflammasome in the pathogenesis of AD and help individualize therapeutic approaches. PMID- 22322006 TI - Diagnosing nonimmediate reactions to cephalosporins. PMID- 22322007 TI - The developmental trajectory of pediatric asthma in 3- to-10-year-olds. PMID- 22322008 TI - A fascinating look at the world with a new microscope. PMID- 22322009 TI - Gut matters: microbe-host interactions in allergic diseases. AB - The human body can be considered a metaorganism made up of its own eukaryotic cells and trillions of microbes that colonize superficial body sites, such as the skin, airways, and gastrointestinal tract. The coevolution of host and microbes brought about a variety of molecular mechanisms, which ensure a peaceful relationship. The mammalian barrier and immune functions warrant simultaneous protection of the host against deleterious infections, as well as tolerance toward harmless commensals. Because these pivotal host functions evolved under high microbial pressure, they obviously depend on a complex network of microbe host interactions. The rapid spread of immune-mediated disorders, such as autoimmune diseases, inflammatory bowel diseases, and allergies, in westernized countries is thus thought to be due to environmentally mediated disturbances of this microbe-host interaction network. The aim of the present review is to highlight the importance of the intestinal microbiota in shaping host immune mechanisms, with particular emphasis on allergic diseases and possible intervention strategies. PMID- 22322010 TI - Familiarity from the configuration of objects in 3-dimensional space and its relation to deja vu: a virtual reality investigation. AB - Deja vu is the striking sense that the present situation feels familiar, alongside the realization that it has to be new. According to the Gestalt familiarity hypothesis, deja vu results when the configuration of elements within a scene maps onto a configuration previously seen, but the previous scene fails to come to mind. We examined this using virtual reality (VR) technology. When a new immersive VR scene resembled a previously-viewed scene in its configuration but people failed to recall the previously-viewed scene, familiarity ratings and reports of deja vu were indeed higher than for completely novel scenes. People also exhibited the contrasting sense of newness and of familiarity that is characteristic of deja vu. Familiarity ratings and deja vu reports among scenes recognized as new increased with increasing feature-match of a scene to one stored in memory, suggesting that feature-matching can produce familiarity and deja vu when recall fails. PMID- 22322011 TI - The lectin Helix pomatia agglutinin recognizes O-GlcNAc containing glycoproteins in human breast cancer. AB - There has been considerable interest in understanding the epitopes that bind the lectin Helix pomatia agglutinin (HPA) in breast cancer as the lectin has been shown to identify glycosylation changes associated with the development of metastatic disease. HPA has previously been shown to recognize aberrant O-linked alpha-N-acetylgalactosamine (GalNAcalpha)/mucin glycosylation in cancer, including exposed Tn epitopes. However, recent glycan-array analysis reported that diverse epitopes are also recognized by the lectin, e.g. consortium for functional glycomics (CFG) data: GalNAcalpha1,3Gal; beta-GalNAc; GlcNAcbeta1,4Gal. The intriguing observations from the CFG array led to this study, in which HPA-binding epitopes were localized and characterized in an in vitro model of breast cancer metastasis. HMT3522 (benign disease), BT474 (primary cancer) and T47D/MCF7 (metastatic cancer) cells were assessed in confocal microscopy-based co-localization studies and a glycoproteomic analysis based on 2 dimensional electrophoresis (2DE), western blotting and mass spectrometry was adopted. HPA binding correlated with levels of integrin alpha6, transcription factors heterogeneous nuclear ribonuclear protein (HnRNP) H1, HnRNP D-like, HnRNP A2/B1 as well as heat shock protein 27 (Hsp27), glial fibrillary acidic protein and enolase 1 (ENO1). These glycoproteins were non-detectable in the non metastatic breast cancer cell lines. The recognition of HnRNPs, Hsp27 and ENO1 by HPA correlated with O-GlcNAcylation of these proteins. Integrin alpha6 was the most abundant HPA glycoprotein in the breast cancer cells with a metastatic phenotype; this concurred with previous findings in colorectal cancer. This is the first report in which HPA has been shown to bind O-GlcNAcylated transcription factors. This class of proteins represents a new means by which HPA differentiates cancer cells with an aggressive metastatic phenotype. PMID- 22322012 TI - A critical examination of the construct of perfectionism and its relationship to mental health in Asian and African Americans using a cross-cultural framework. AB - Although the bulk of the research literature on the construct of perfectionism and its relationship to mental health in the last 20 years has focused predominantly on Caucasian American samples, researchers are paying increasing attention to understanding perfectionism's dimensions across ethnicities. Given this momentum, the purpose of this paper is to use a cross-cultural framework to review published studies assessing perfectionism in members of an ethnic minority group living in the United States. Research to date has focused exclusively on Asian and African American samples and we organize our review by separating this literature into those studies that use level and structure-oriented cross cultural approaches. Structure-oriented approaches empirically explore the phenomenology and/or correlates of perfectionism within each ethnic group whereas level-oriented approaches examine the relative magnitude of perfectionism's levels across groups. The last section of the review critically examines the strength of the evidence in support of researchers' arguments that certain sociocultural factors, such as collectivism and parenting style, influence perfectionism's expression and implications for ethnic minorities. Throughout the review, we offer a series of steps researchers can take to foster our understanding of perfectionism and its impacts using a cross-cultural perspective. PMID- 22322013 TI - Hoarding versus collecting: where does pathology diverge from play? AB - A new diagnosis termed Hoarding Disorder has been proposed for inclusion in the upcoming DSM-5 to cover the majority of cases where severe hoarding occurs in the absence of, or independently from other mental disorders. Much effort has been directed to ensuring that the proposed criteria discriminate Hoarding Disorder from other mental disorders, particularly those historically associated with hoarding (e.g. OCD, OCPD). Considerably less attention, however, has been paid to addressing the suitability of the proposed criteria for effectively differentiating pathological hoarding from normative collecting behavior. This is crucial in order to avoid false positives or the overpathologization of this widespread human activity. Collecting behavior mirrors many of the core features of hoarding (e.g. the acquisition of and emotional attachment to a potentially large number of objects), is highly prevalent and is generally considered a normative form of object amassment; as such, it represents a valid population with which to explore the diagnostic boundaries of Hoarding Disorder. Examination of the collecting literature, within the context of the hoarding diagnostic criteria, indicates that, for the majority of collectors, a diagnosis of Hoarding Disorder is likely to be effectively ruled out. For a minority of 'extreme' collectors, a diagnosis may potentially be adequate. This review highlights the similarities and differences between hoarding and collecting and offers suggestions for further research in this group. PMID- 22322014 TI - The 35% carbon dioxide test in stress and panic research: overview of effects and integration of findings. AB - The carbon dioxide test--a vital capacity breath of air containing 35% carbon dioxide (CO(2))--provokes panic attacks in many individuals with panic disorder (PD). It has thus been extensively used as an experimental model of panic and less frequently as a clinical method of provoking symptoms for interoceptive exposure treatment. Recently, stress researchers have suggested another use for the CO(2) test: that of an acute physiological stressor indexing the human stress response. The purpose of this review is to synthesize findings about the effects of the CO(2) test from both the panic and stress literatures in order to advance understanding about this increasingly popular test. Both panic and stress researchers have examined the fleeting effects of the CO(2) test, finding that the test engenders transient breathlessness, dizziness, and minor anxiety in most participants and panic attacks in those with or at risk for PD. Physiological measurements after the test indicate a brief homeostatic disruption in many bodily systems, including increased respiration, systolic blood pressure, and noradrenaline, and decreased heart rate. Most studies indicate increased cortisol. Possible benefits of integrating findings from the panic and stress research lines, given their common use of the CO(2) test, are discussed. PMID- 22322015 TI - Fibrin nanoconstructs: a novel processing method and their use as controlled delivery agents. AB - Fibrin nanoconstructs (FNCs) were prepared through a modified water-in-oil emulsification-diffusion route without the use of any surfactants, resulting in a high yield synthesis of fibrin nanotubes (FNTs) and fibrin nanoparticles (FNPs). The fibrin nanoconstructs formed an aligned structure with self-assembled nanotubes with closed heads that eventually formed spherical nanoparticles of size ~250 nm. The nanotubes were typically ~700 nm long and 150-300 nm in diameter, with a wall thickness of ~50 nm and pore diameter of about 150-250 nm. These constructs showed high stability against aggregation indicated by a zeta potential of -44 mV and an excellent temperature stability upto 200 degrees C. Furthermore, they were found to be enzymatically degradable, thereby precluding any long term toxicity effects. These unique fibrin nanostructures were analyzed for their ability to deliver tacrolimus, an immunosuppressive drug that is used widely to prevent the initial phase of tissue rejection during allogenic transplantation surgeries. Upon conjugation with tacrolimus, a drug encapsulation efficiency of 66% was achieved, with the in vitro release studies in PBS depicting a sustained and complete drug release over a period of one week at the physiological pH of 7.4. At a more acidic pH, the drug release was very slow, suggesting their potential for oral-intestinal drug administration as well. The in vivo drug absorption rates analyzed in Sprague Dawley rats further confirmed the sustained release pattern of tacrolimus for both oral and parenteral delivery routes. The novel fibrin nanoconstructs developed using a green chemistry approach thus proved to be excellent biodegradable nanocarriers for oral as well as parenteral administrations, with remarkable potential also for delivering specific growth factors in tissue engineering scaffolds. PMID- 22322016 TI - "Listening to each other": a project to improve relationships with underserved members of our society. PMID- 22322017 TI - The feminization of dentistry: implications for the profession. AB - Over the last 40 years, the proportion of women in dentistry has been rising steadily, raising questions about the effects of this feminization on the profession. A review of the literature, although limited, highlights potentially important areas related to gender, including impact on work hours, practice models, professional incomes, the dentist-patient relationship, clinical philosophies, specialty practice, academia and leadership. Although cohorts of predominantly female dentists are only beginning to enter the workforce and, thus, it is difficult to predict the long-term effects, some trends are evident: women are less likely than men to own their practice; women may work 4-6 fewer hours a week and see fewer patients; there is a pay differential; female general practitioners and specialists appear more likely to work in urban centres; and women are less prominent in the specialties, academia and leadership roles. Thus, the profession may shift toward less entrepreneurship, more urbanization and, possibly, fewer clinical hours available to the population as a result of feminization. With the ultimate goal of excellence in patient care, this may entail increases in student enrolment, formal incentives for practice relocation to rural communities, more business education and policies to modify advanced education and training for women with children. This knowledge, although still not robust, is relevant for policy, educational institutions and professional governing bodies. PMID- 22322018 TI - Cochrane review reveals benefits of flossing for reducing gingivitis. PMID- 22322019 TI - Dimensional accuracy of 2 irreversible hydrocolloid alternative impression materials with immediate and delayed pouring. AB - OBJECTIVE: To assess dimensional accuracy and stability of 2 irreversible hydrocolloid alternative impression materials with immediate and delayed pouring. METHODS: Two alternative impression materials, AlgiNot FS and Position Penta Quick, were compared with a traditional irreversible hydrocolloid, Jeltrate Plus antimicrobial alginate. Impressions were made of a metal model with 4 cylinders of known dimensions, with pouring performed immediately or after 4 hours of storage. A digital micrometer was used to measure cylinder diameter on the model and the poured casts. Dimensional changes were analyzed according to American National Standards Institute/American Dental Association (ANSI/ADA) Specification 19 (2004 version) (alpha=0.05). RESULTS: There were significant differences among the 3 materials, between the 2 pour times and as a function of storage time (multivariate analysis of variance, p<0.001). One-way analysis of variance revealed no significant differences between the 2 alternative impression materials, but changes for these materials differed significantly from those for the traditional impression material for immediate (p<0.05) and 4-hour (p<0.001) pouring. Linear dimensional changes for the 2 substitute materials were within the limits of the ANSI/ADA specification. CONCLUSIONS: With immediate pouring, both alternative impression materials exhibited minimal dimensional changes, which were maintained or reduced with 4-hour pouring. For both pouring times, these changes were less than 0.5%. CLINICAL SIGNIFICANCE: The minimal dimensional changes observed with these irreversible hydrocolloid alternative impression materials after 4 hours of storage may save chairside time and help to produce accurate results for procedures such as partial denture framework, surgical guides, and pediatric and orthodontic devices. PMID- 22322020 TI - Real communication leads to real trust. PMID- 22322021 TI - Revascularization of immature permanent incisors after severe extrusive luxation injury. AB - Pulp necrosis is an uncommon sequel to extrusive luxation in immature teeth with incomplete apical closure. In this report, we describe the management of severely extruded immature maxillary incisors and the outcome of revascularization to treat subsequent pulp necrosis. An 8.5-Year-old boy with severe dentoalveolar trauma to the anterior maxillary region as a result of a fall was provided emergency treatment consisting of reduction of the dislodged labial cortical bone and repositioning of the central incisors, which had suffered extrusive luxation. When he presented with spontaneous pain involving the traumatized incisors a week later, the teeth were treated via a revascularization protocol using sodium hypochlorite irrigation followed by 3 weeks of intracanal calcium hydroxide, then a coronal seal of mineral trioxide aggregate and resin composite. Complete periradicular healing was observed after 3 Months, followed by progressive thickening of the root walls and apical closure. Follow-up observations confirmed the efficacy of the regenerative treatment as a viable alternative to conventional apexification in endodontically involved, traumatized immature teeth. PMID- 22322022 TI - A talon cusp mistaken for a mesiodens: case report. AB - We present the case of an 8-year-old boy with a talon cusp associated with a permanent maxillary central incisor that was mistaken for a supernumerary tooth. The importance of early and correct diagnosis of a talon cusp is stressed. Diagnosis and treatment planning strategies are discussed. PMID- 22322023 TI - [Care and treatment of elderly skin disorders, especially pressure ulcers]. PMID- 22322024 TI - [Parkinson's disease in elderly]. PMID- 22322025 TI - [Vertigo in the elderly]. PMID- 22322026 TI - [Hematological malignancies in the elderly]. PMID- 22322027 TI - [Clinical and therapeutic features of infectious diseases in elderly patients]. PMID- 22322028 TI - [Musculoskeletal Ambulation Disability Symptom Complex (MADS)]. PMID- 22322029 TI - [Japanese guidelines for the management of stroke 2009]. PMID- 22322030 TI - [The new guideline for dementia]. PMID- 22322031 TI - [Treatment guide for diabetes]. PMID- 22322032 TI - [Guideline for diagnosis and treatment for COPD]. PMID- 22322033 TI - [Guideline for the managements of hypertension -blood pressure control for the elderly hypertension]. PMID- 22322034 TI - [Dementia, depression and delirium in the elderly]. PMID- 22322035 TI - [Fall and fracture of the elderly people]. PMID- 22322036 TI - [Malnutrition]. PMID- 22322037 TI - [Prevention and management of geriatric syndrome; aspiration and pneumonia]. PMID- 22322038 TI - [Evaluation of laparoscopy-assisted surgery in elderly colorectal cancer patients]. AB - AIM: This study evaluated the safety and efficacy of laparoscopic surgery in elderly colorectal cancer patients. METHODS: A total of 270 colorectal cancer patients over 75 years old who had undergone laparoscopy-assisted colectomy (LAC, 81 patients) or open colectomy (OC, 189 patients) between 2000 and 2009 were retrospectively analyzed regarding clinicopathological and surgery-related factors, perioperative course and pre- and postoperative complications. RESULTS: Early cancers or smaller tumors were treated more frequently by LAC than by OC. LAC tended to take a longer operative time but was similar to OC in terms of the degree of lymph node dissection and number of lymph nodes. The LAC group showed less blood loss, earlier ambulation, earlier eating and drinking, earlier passage of flatus and feces, a shorter hospital stay and lower postoperative leukocyte count (days 1 and 3) and CRP (day 3). The LAC group was similar to the OC group in preoperative complications (80.2% vs. 81.1%) but less postoperative complications (6.7% vs. 12.2%). The postoperative complications were mainly deliria and respiratory complications, but there was no anastomotic leakage or operative deaths. CONCLUSIONS: LAC was relatively safe in elderly patients and is associated with earlier postoperative recovery. The abdominal wall damage caused by surgery was considered one reason for the delay of patient recovery. LAC showed reduced damage and better postoperative course. These results indicate expanded indications of LAC for elderly colon cancer patients. PMID- 22322039 TI - [Relationship between EPA or EPA/AA and arteriosclerosis in elderly patients over 80 years old]. AB - AIM: Fish oil is associated with decreased arteriosclerosis, cardiovascular disease and the prevention of cellular aging. Most studies of n-3 PUFA (polyunsaturated fatty acid) have been conducted in patients under 80 years of age, and there are few studies of subjects >=80 years of age. This study investigated the relationship between eicosapentaenoic acid (EPA) or arachidonic acid (AA) and arteriosclerosis in elderly patients >=80 years of age. METHOD: We enrolled 150 patients >=80 years of age (average, 85+/-4 years) not taking EPA that presented or were admitted to our hospital. Their EPA or AA levels were measured to investigate the relationship between EPA or EPA/AA and cardiovascular disease or cerebrovascular disease. In addition, we investigated whether the ratio of EPA/AA was associated with estimated glomerular filtration rate (eGFR). RESULTS: The mean EPA level was 55.9+/-34.5 ug/dL, the mean AA level was 145.1+/ 45.4 ug/dL and the mean EPA/AA was 0.40+/-0.24 (mean+/-SD). There were no significant differences between the EPA/AA and EPA values in patients with cardiovascular disease and those in patients without cardiovascular disease. Moreover, there were no significant differences between the EPA/AA and EPA values in patients with cerebrovascular disease and those in patients without cerebrovascular disease. There were no statistically significant correlations between EPA/AA or EPA and eGFR. CONCLUSION: Individuals may achieve a peak value of EPA or EPA/AA in their 70s and there is little change in those levels in patients aged over 80. No relationship was identified between EPA/AA and arteriosclerosis in subjects aged over 80 compared with those under 80 years of age. PMID- 22322040 TI - [Relationship between care staff generativity and perceived job competence in elderly nursing homes]. AB - AIM: According to Erikson's theory of ego development, generativity represents one task of adulthood. Generativity is defined as a concern for establishing and passing on well-being to future generations. The present study aimed to characterize the relationship between staff member generativity and perceived job competence in elderly nursing homes, and to determine the professional value of elderly care. METHODS: A total of 367 care staff at 13 nursing homes for elderly people participated in the present study, the design of which was a questionnaire survey. The survey addressed topics related to generativity and perceived job competence. Path analysis was conducted to examine the relationship between generativity and perceived job competence. RESULTS: Perceived job competence was related to age (beta=0.19, p<0.01) and occupational period (beta=0.14, p<0.05), and generativity was related to perceived job competence (beta=0.67, p<0.001). These results also suggest that perceived job competence promotes generativity development. CONCLUSIONS: The development of staff generativity in nursing homes may yield work satisfaction and elevated vocational identity. PMID- 22322041 TI - [Association of location of deep venous thrombosis and d-dimer value in acute intracerebral hemorrhage]. AB - AIM: We investigated the association of the presence and the location of deep venous thrombosis (DVT) with D-dimer value in acute intracerebral hemorrhage (ICH). METHODS: We analyzed the data regarding DVT in patients with ICH. Based on an ultrasonographic examination 2 weeks after the occurrence of ICH, the patients were divided according to the presence/absence and the location of DVT, i.e. no evidence of DVT (n-DVT), calf DVT (c-DVT), and proximal DVT (p-DVT). D-dimer value was measured 2 weeks later and compared among the groups. RESULTS: The numbers of patients with n-DVT, c-DVT and p-DVT were 27, 19, and 2, respectively. Univariate analysis indicated that D-dimer values were significantly different between patients with n-DVT and c-DVT and between patients with n-DVT and p-DVT (p<0.05, respectively). The cut-off value for estimating the presence of DVT and p-DVT was 3.9 ug/mL and 18.5 ug/mL, respectively. CONCLUSION: D-dimer value assessment after 2 weeks may be associated with the presence and the location of DVT in patients with ICH. PMID- 22322042 TI - [Examination of effects of alfacalcidol vitamin D supplement and renal function on improvement in the physical fitness of pre-frail elderly persons attending a nursing care prevention class]. AB - AIM: A characteristic condition of pre-frail elderly people is decreased mobility, which is associated with vitamin D levels and renal function. The aim of this study was to examine the association between physical fitness improvement and vitamin D levels, vitamin D supplements, and renal function in pre-frail elderly people. METHODS: We conducted a longitudinal study in 2 towns from June 2006 to December 2009. Subjects consisted of 177 community-dwelling pre-frail elderly people aged 65 years and over (mean+/-standard deviation [SD]: 76.4+/-5.5 yrs) who attended a nursing care prevention program for 3 months. An interview was conducted based on a questionnaire. Serum levels of intact parathyroid hormone (iPTH), 25-hydroxyvitamin D(25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)(2)D), creatinine, and calcium were measured. eGFR (ml/min/1.73 m(2)) was calculated using a new formula. Alfacalcidol 1 ug/day was administered to subjects for 3 months, and we assumed that the elderly who took vitamin D (VD) of more than 80% of the recommended daily allowance to be the VD group. Walking ability, balance, and muscle strength physical fitness tests were performed. RESULTS: The prevalence of eGFR <60.0 ml/min/1.73 m(2) was about 24.3%, and that of 25(OH)D <75 nmol/L was 86.4%. Pre-eGFR level and vitamin D supplementation with FR, pre-eGFR and pre 25(OH)D >=45 nmol/L were associated with improvement in the timed up and go (TUG) test, pre-25(OH)D level (<50 nmol/L, >=50 nmol/L) was associated with the tandem stance test, pre 25(OH)D level (<67.5 nmol/L, >=67.5 nmol/L) was associated with the alternate step and 5 chair sit-to-stands tests, and post 1,25(OH)(2)D (<44 pg/ml, >=44 pg/ml) was associated with the tandem walk tests. CONCLUSIONS: These results suggest that the assessment of renal function and maintenance of appropriate vitamin D levels are important for the independent living of pre-frail elderly people. Ideally, a 25(OH)D level greater than 67.5 nmol/L is preferable. PMID- 22322043 TI - [The effects of Tai-chi exercise for the prevention of long-term care in community-dwelling frail elderly people -new care-need certification and mortality-]. AB - AIM: The purpose of this study was to examine the effects of a Tai Chi Yuttari exercise based care prevention program aimed at frail elderly people on new care need certification and mortality. METHODS: Participants were elderly individuals (>=65 years of age) who lived in Kitakata City and who had experienced a fall in the past year but were not receiving support or long-term care. Those who agreed to participate in the exercise program were the intervention group (n=34), and those who did not participate were the control group (n=84). The intervention program was carried out once a week for a total of 15 times during the period spanning December 5, 2006 to March 22, 2007. In the intervention group we measured and analyzed changes in physical functions and administered a questionnaire before and after the intervention. We confirmed any deaths and determined whether certification for long-term care had been issued to the participants, in March 2010. RESULTS: New care-need certification was issued to 2 participants (6.3%) in the intervention group and 19 (24.1%) in the control group. Logistic regression analysis revealed that participants in the intervention group tended to require less new certification than those in the control group (p=0.098). There was no significant difference in the number of deaths between the intervention (2 participants; 5.9%) and control (5 participants; 6.0%) groups. We observed significant changes between pre- and post intervention on several variables, including motor fitness scale, maximum walking speed over 10 meters, functional reach test, ability to stand after a long period of sitting, and maximum one step width. CONCLUSION: The Tai Chi Yuttari-exercise based intervention program for frail elderly people reduced the need for new care need certification and was useful as a care prevention program. PMID- 22322044 TI - [A case of pulmonary dirofilariasis with a single nodule on an apical lesion of the right upper lobe]. AB - A 75-year-old man with chronic gastritis and gastro-esophageal regurgitation syndrome was admitted to our hospital complaining of continuous productive cough, and an abnormal shadow was noted on a chest X-ray film. Chest computed tomography revealed a nodule 2.8 cm in diameter with a regular margin on the right apex. Fiberoptic bronchoscopy was performed, but did not yield a definitive diagnosis. We suspected primary lung cancer, and therefore, lung partial resection was performed under thoracoscopic surgery. The intraoperative pathological findings revealed inflammatory granuloma with necrosis, and pulmonary dirofilariasis was finally diagnosed. Pulmonary dirofilariasis is an important differential diagnosis in elderly patients with a chest abnormal nodular shadow. Lesions have been reportedly observed in the peripheral portion of the right lower lobe in many previous reports. However, in this case, a nodular lesion was noted in the right apex. PMID- 22322046 TI - [Scheme for inter-professional network development in the community]. PMID- 22322045 TI - [Comparison of journal articles regarding physical restraint between the Japanese and American Geriatrics Societies]. PMID- 22322047 TI - Quality of intrathecal baclofen from different sources. AB - OBJECTIVE: To compare the quality of intrathecal baclofen obtained from a national compounding pharmacy (AnazaoHealth) with the manufactured product (Lioresal) with regard to accuracy and precision of baclofen concentration, and the content of the baclofen degradation product, 4-(4-chlorophenyl)-2 pyrrolidinone (PYR). DESIGN: Samples of baclofen used for refilling intrathecal pumps were placed in 1.2-mL silicone gasket-sealed cryogenic vials and stored at or lower than -25 degrees C. Each sample was a different lot number (Lioresal) or prescription number (AnazaoHealth). The laboratory was blinded to the source of the solutions. Coupled with electrospray ionization-mass spectrometry analyte confirmation, quantitation of baclofen and PYR in each sample was performed in duplicate by using high-performance liquid chromatography with ultraviolet detection via a photodiode array detector. SETTING: Outpatient clinic. PARTICIPANTS: Patients with intrathecal baclofen pumps. MAIN OUTCOME MEASURES: Accuracy and precision of baclofen concentration, and concentration of PYR. RESULTS: The difference of mean concentrations from expected concentrations of 500 and 2000 MUg/mL were significantly greater for samples from AnazaoHealth compared with Lioresal. Values are shown as mean (+/- standard error), with n the number samples, for AnazaoHealth compared with Lioresal: (537.1 +/- 6.7 MUg/mL [n = 8] versus 515.6 +/- 0.82 MUg/mL [n = 5]; P = .034, respectively) and (2211.4 +/ 21.6 MUg/mL [n = 12] versus 2055.3 +/- 8.7 MUg/mL [n = 4]; P = .004, respectively). AnazaoHealth samples with expected concentration of 4000 MUg/mL were 3987.7 +/- 79.9 MUg/mL, n = 7. All 9 Lioresal samples were within 5% of the expected concentration. Of 27 AnazaoHealth samples, 22 were more than 5%, and 8 were more than 10% different from the expected concentration. No PYR was detected in any sample from AnazaoHealth. All samples of Lioresal contained PYR, but all solutions contained less PYR than 1% of the baclofen concentration. CONCLUSIONS: Lioresal was more accurate in concentration and more precise among batches than compounded intrathecal baclofen but had higher levels of PYR. PMID- 22322048 TI - [The advance in surgical treatment of cerebral vascular diseases]. PMID- 22322049 TI - [Clinical characteristics and surgical outcomes of 3094 patients with cerebral arteriovenous malformation]. AB - OBJECTIVE: To retrospectively analyze the clinical characteristics and surgical outcomes of 3094 patients with cerebral arteriovenous malformation (AVM) over a course of 53 years. METHODS: The clinical data of 3094 consecutive AVM patients from July 1956 to April 2009 were collected and analyzed. The parameters included age (at diagnosis), gender, initial onset, Spetzler-Martin grade, relationship of lesion volume and blood, AVM with aneurysm, AVM with varices, surgical outcomes and mortality. RESULTS: Cerebral AVMs were more commonly diagnosed at a mean age of 27 +/- 13 years old (range: 12 - 38). Hemorrhage (n = 1617, 52.26%), headache (n = 550, 17.78%) and seizure (n = 397, 12.83%) were the first three common presentations. A total of 1486 patients were estimated by Spetzler-Martin grading system. And the percentage of grades 2 - 4 patients was highly than that of other levels. The smaller the lesion volume, the greater risk of intracranial hemorrhage. Varices were found in 26 (0.84%) of 3094 AVM patients. And 12 (46.15%) patients with varices had a hemorrhage at presentation. Aneurysm was found in 66 (2.13%) of 3094 AVM patients. And 38 (57.58%) patients with varices had a hemorrhage at presentation. Among them, 2013 patients received microsurgery treatment. The outcomes were recovery (83.51%), excellence (12.42%), no change (0.60%), deterioration (0.30%) and death (3.18%). The surgical mortality of the patients with a hemorrhage at presentation was 5.19%. CONCLUSION: The first presentation of AVM is commonly apparent at a young age. And intracranial hemorrhage occurs often at dominant positions. AVM is one of the important reasons for spontaneous intracranial hemorrhage in youth. And the risk of hemorrhage is present for a patient's whole life. Microsurgery treatment can remove the lesion and eliminate the risk of hemorrhage immediately. With the applications of neurosurgery, navigation, ultrasound and intraoperative fluorescence angiography, the surgical treatment of AVM becomes safer and more reliable. PMID- 22322050 TI - [Intracranial aneurysms in childhood and adolescence]. AB - OBJECTIVE: To assess the radiological characteristics and therapeutic strategies of intracranial aneurysms in childhood and adolescence. METHODS: From our dedicated aneurysmal patient databank, the investigators reviewed 39 consecutive children and adolescents with 44 intracranial aneurysms. There were 24 boys and 15 girls. RESULTS: Twenty-two patients underwent endovascular treatment. Among them, 8 patients received microsurgical therapy. Aneurysms became spontaneously thrombosed before therapy in 3 patients. One patient died pre-operatively from a re-rupture of aneurysm. And 5 cases were not treated at all. CONCLUSION: Intracranial aneurysms in childhood and adolescence have many clinical and radiological characteristics: (1) remarkable male predominance; (2) middle cerebral artery is the most common site for aneurysms; (3) there is a high prevalence of giant, traumatic, dissecting and fusiform aneurysms; (4) both microsurgical approaches and endovascular treatment were effective. For some giant complex intracranial aneurysms, parent arterial occlusion or EC-IC (extracranial-intracranial) bypass is the best therapeutic choice. A majority of patients may have favorable outcomes. PMID- 22322051 TI - [Microsurgery treatment with aneurysm on the top of basilar artery]. AB - OBJECTIVE: To explore the efficacy and method of microsurgery for aneurysm on the top of basilar artery. METHODS: The investigators analyzed retrospectively the clinical data of 8 microsurgical patients with aneurysm on the top of basilar artery from May 2007 to September 2010. There were 5 males and 3 females with an average age of 52.6 years old. Six of 8 cases underwent clipping of aneurysm while other 2 patients received superficial temporal artery-radial artery posterior cerebral artery bypass grafting surgery and clipping of aneurysm. RESULTS: On the basis of GOS (Glasgow outcome score), the postoperative recovery was excellent in 7 patients. And 1 patient suffered insufficiency of oculomotor nerve similarly as preoperatively. CONCLUSION: The surgical procedures for aneurysm of basilar artery are so complicated as to lead to many complications. A wise choice of operative approaches may yield a better outcome. PMID- 22322052 TI - [Ultrasound-guided percutaneous microwave ablation in the treatment of diffuse adenomyosis]. AB - OBJECTIVE: To assess the feasibility of percutaneous microwave ablation in the treatment of diffuse adenomyosis. METHODS: With a mean age of 39.2 years old, 16 patients with symptomatic adenomyosis underwent percutaneous microwave ablation (PMA). The symptoms included severe dysmenorrheal and anemia. The definite diagnosis was made by magnetic resonance (MR) imaging. Two microwave therapeutic antennas were inserted into the myometrium with adenomyosis. The microwave emission was seized when the ablated zone was over half of the total lesion. The complications, side effects and early therapeutic effects were observed during the period of treatment and at 3 and 6 months post-treatment. RESULTS: The average ablation duration was 700 s. The average ablated area was 72% (range: 60% - 80%). None of the patients developed complications during and after ablation. Fifteen patients had normal menstrual onset during the month of receiving ablation and one case at Day 30. The amount of menstrual bleeding was less than that before treatment. Dysmenorrhea disappeared after treatment in 13 cases, relieved markedly in 2 and no improvement in 1. The endometrial ectopic growth was not observed after treatment. CONCLUSION: The early clinical efficacy of PMA under ultrasound guidance is definite in the treatment of adenomyosis. The symptoms may be eliminated or effectively relieved after treatment. Easy to perform, minimal invasive and safe, the procedure of PMA is an effective therapeutic modality for adenomyosis with the preservation of uterus. PMID- 22322053 TI - [Clinical characteristics and perinatal outcomes of non-overweight/obese pregnant women with polycystic ovary syndrome]. AB - OBJECTIVE: To determine clinical characteristics and perinatal outcomes of non overweight/obese (pre-pregnancy body mass index BMI < 24 kg/m(2)) pregnant women with polycystic ovary syndrome (PCOS). METHODS: The screening of PCOS was performed when they were at first prenatal visit in Beijing Obstetrics and Gynecology Hospital, Capital Medical University from May, 2008 to July, 2010.61 PCOS women of pregnancy women with BMI < 24 kg/m(2) were considered as the study subjects, and 122 pregnant women without PCOS matched by age and pre-pregnancy body mass index (BMI) were selected as the control ones. Patients with history of pre-pregnancy diabetes, hypertension, cardiovascular disease, renal diseases and multiple pregnancies were excluded from the study. We followed pregnancy outcomes of two groups until delivery. RESULTS: Significantly higher total cholesterol, triglycerides concentrations and low-density lipoprotein cholesterol concentrations were found in the PCOS group than in the controls. PCOS women with BMI < 24 kg/m(2) had significantly higher rates of GDM (27.9% (17/61)) and pre eclampsia (13.1% (8/61)) compared with the controls (15.6% (19/122), 1.6% (2/122)), P < 0.05, < 0.01, respectively. No statistical significance was found in prevalence of pregnancy-induced hypertension, polyhydramnios, oligohydramnios, macrosomia, premature rupture of membranes, placental abruption, macrosomia, fetal death and neonatal congenital abnormality between the two groups (all P > 0.05). CONCLUSIONS: It is at increased risk of GDM and pre-eclampsia in non overweight/obese PCOS women, this risk seemed to be due to PCOS itself rather than obesity. PMID- 22322054 TI - [Values of serum copper and serum free copper in the diagnosis and monitoring of Wilson's disease and its carriers]. AB - OBJECTIVE: To explore the values of serum copper and serum free copper in the diagnosis of Wilson's disease (WD), its carrier and viral hepatitis and explore the guiding significance of monitoring serum copper in the treatment of WD. METHODS: A total of 80 WD patients (hepatic type, n = 60; encephalic type, n = 20), 30 carriers, 20 patients with viral hepatitis were enrolled and their levels of serum copper were determined. The neural symptoms were scored by modified Young grade. Hemogram, hepatic functions, blood clotting functions, serum copper and urinary copper were tested throughout all 8 courses of treatment with sodium dimercaptopropane sulfonate (DMPS). The patients were treated with zinc after discharging. All data were analyzed. RESULTS: The free serum copper increased in the patients with WD (0.17 mg/L +/- 0.04 mg/L), carriers (0.13 mg/L +/- 0.03 mg/L) and severe viral hepatitis (0.12 mg/L). A slight increase was also observed in the WD carriers. The level of serum copper was correlated with hepatic functions but not with the severity of neural symptoms. The serum copper increased in the patients with no improvement of neural symptoms. However, the serum copper decreased in the WD patients with the improvement of neural symptoms. The serum copper was stabilized at approximately 0.2 mg/L during the long-term treatment period. CONCLUSION: There is auxiliary diagnosis significance of serum copper in the determination of WD. Hepatic functions in hepatic type WD affect the level of serum copper. The serum copper of encephalic type WD can not indicate the severity of neural symptoms. The elevated level of serum copper indicates a poor prognosis. The serum copper is an effective marker in monitoring the development and therapeutic efficacy of the disease. PMID- 22322055 TI - [Clinical analysis of 47 cases of synchronous double primary carcinomas of esophagus and cardia]. AB - OBJECTIVE: To explore the clinical features and prognosis of the patients with synchronous double primary malignancy of esophagus and cardia. METHODS: The clinical data of patients with synchronous primary esophageal and cardiac carcinomas undergoing surgery at our hospital between April 1988 and April 2009 were retrospectively reviewed. All data were analyzed by the SPSS 15.0 software. The overall survival rates (OS) were calculated and compared with the Kaplan Meier method and the Log-rank test. The prognostic factors were identified by Cox's hazard regression model. RESULTS: Among all 47 cases, esophageal carcinoma was missed preoperatively in 1 patients and cardiac carcinoma in 12. The 1-, 3- and 5-year overall survival rates (OS) of the whole group were 81.5%, 49.1% and 34.3% respectively. And the median survival time was 33 months. The univariate analysis of prognostic factors showed that radical resection, N stage of esophageal carcinoma (2009), N stage of cardiac carcinoma (2009) and TNM stage of cardiac carcinoma (both 2002 and 2009) might influence the long-term survival. However, according to the multivariate analysis, only radical resection and N stage of cardiac carcinoma (2009) were independent prognostic factors. CONCLUSION: With preoperative combined examination of esophagography and esophagoscopy and thorough intraoperative detection, the clinicians may reduce the rate of missed diagnosis for synchronous double primary esophageal and cardiac carcinomas. Radical resection of primary lesions and thorough dissection of locoregional lymph nodes may improve the patient survival. PMID- 22322056 TI - [Relationship between sphingosine kinase 1 expression and tumor invasion, metastasis and prognosis in gastric cancer]. AB - OBJECTIVE: To explore the clinical significance of sphingosine kinase 1 (SPHK1) in the invasion, metastasis and prognosis of gastric cancer. METHODS: Immunohistochemistry was employed to analyze the expression of SPHK1 in 206 clinicopathologically characterized gastric cancer cases from January 2001 to December 2005 at Zhejiang Provincial People's Hospital. RESULTS: SPHK1 protein was detected in 3 (7.5%) of 40 human non-tumor mucosa. All samples expressed the protein at a low level. SPHK1 protein was detected in 181 (87.9%) of 206 human gastric cancer cases. An elevated expression of SPHK1 protein was detected in 126 (61.2%) tumors. And SPHK1 protein was up-regulated in gastric cancer lesions compared with adjacent noncancerous tissues (P = 0.001). The expression of SPHK1 was correlated with the depth of invasion, lymph node metastasis, distant metastasis and TNM stage (P = 0.039, 0.003, 0.020, 0.003). In stages I-II and III, the 5-year survival rate of the patients with a high expression of SPHK1 was significantly lower than those with a low expression (53.6% (15/28) vs 68.6% (24/35), 7.8% (6/77) vs 30.8% (12/39), P = 0.009, 0.006). In stage IV, the expression of SPHK1 was not correlated with the 5-year survival rate (P > 0.05). Further multivariate analysis suggested that lymph node metastasis, distant metastasis, TNM stage and the up-regulation of SPHK1 were independent prognostic indicators for gastric cancer. CONCLUSION: The expression of SPHK1 in gastric cancer is significantly associated with lymph node metastasis, distant metastasis and a poor prognosis. SPHK1 may become a useful marker of predicting tumor progression and prognosis. PMID- 22322057 TI - [Direct dissection of urogenital diaphragm in abdominoperineal resection]. AB - OBJECTIVE: To compare the clinical outcomes of two operative approaches of perineal dissection in rectal carcinoma undergoing abdominoperineal resection. METHODS: A randomized controlled trial was conducted in a total of 126 patients with rectal cancer undergoing the Miles operation from June 2007 to June 2011 at Henan Provincial Cancer Hospital. They were divided into 2 groups. One group (Group A) underwent a direct dissection of urogenital diaphragm while another group (Group B) received the traditional operative method. And the duration of perineal surgery, rupture of rectum or tumor, urethral injury and the post operative rate of perineal hemorrhage were compared between 2 groups. RESULTS: Group A had a shorter duration of perineal surgery ((16 +/- 5) min vs (23 +/- 5) min, P = 0.032). And the differences were significant statistically. However the rupture of rectum or tumor, urethral injury and the post-operative rate of perineal hemorrhage were equivalent for two groups (1 vs 5, 2 vs 5, 0 vs 1, 1 vs 3, all P > 0.05). CONCLUSION: A direct dissection of urogenital diaphragm offers more clinical advantages over the traditional operative method in abdominoperineal resection. PMID- 22322058 TI - [Influencing factors of long-mid term efficacy following percutaneous vertebroplasty in patients with osteoporosis]. AB - OBJECTIVE: To determine the therapeutic efficacy and the influencing factors for the long/middle-term outcomes of percutaneous vertebroplasty (PVP) in the treatment of painful osteoporotic vertebral compression fractures (OVCFs). METHODS: This prospective study recruited a total of 131 consecutive OVCF patients treated with PVP at a single institution from March 2005 to December 2009. There were 106 females and 25 males. Pre- and postoperative evaluations included a visual analog scale (VAS) for pain, the Roland-Morris disability questionnaire (RDQ) scores and patient activity levels. Various factors probably correlated with long-mid term efficacy were also analyzed. RESULTS: Both VAS and RDQ scores decreased significantly (P < 0.05). And the activity levels showed significant post-therapeutic improvement (P < 0.01); Univariate and multivariate analysis showed that the influencing factors for the long/middle-term efficacy were age, number of OVCF(s) per time, activity level after discharge and newly occurring OVCF (Z = -2.03, -2.68, 5.38 and -1.73; P = 0.043, 0.007, 0.001 and 0.034 respectively). CONCLUSION: PVP is an efficient pain-relieving procedure. The long/middle-term efficacy after PVP is mostly correlated with both the patient age and the natural course of underlying conditions. PMID- 22322059 TI - [Clinical and neuroimaging features of central nervous system impairments in acute intermittent porphyria]. AB - OBJECTIVE: To analyze the clinical and neuroimaging features of central nervous system impairments in acute intermittent porphyria, and explore the possible mechanisms. METHODS: Six cases with intracranial lesions at our hospital from 1991 to 2011 and 13 cases reported in literatures were retrospectively reviewed. RESULTS: The clinical manifestations of central nervous system impairments included seizures, unconsciousness and cortical blindness, etc. EEG (electroencephalogram) showed slow wave or normal. CSF (cerebrospinal fluid) test indicated slightly higher or normal level of CSF protein. Neuroimaging studies showed two types of intracranial lesions. One type (n = 4) mainly affected the cortex and subcortical white matter, especially involving white matter. Another type (n = 2) affected the deep nuclei such as caudate, putamen and thalamus symmetrically. The symptoms of 13 cases reported in literature with central nervous system impairments included unconsciousness, hallucinations, seizures and cortical blindness. Their neuroimaging manifestations were similar with those of the patients at our hospital. Two additional cases showed predominantly cerebral cortex lesions with no involvement of white matter. CONCLUSION: Acute intermittent porphyria can affect central nervous system, peripheral nervous system and autonomic nervous system. The neuroimaging features of brain may be lesions located in cortex, subcortical white matter and deep nuclei with different mechanisms. A correct diagnosis and a treatment decision should be made during an early stage. PMID- 22322060 TI - [Surgical treatment strategies for severe cervicothoracic kyphosis]. AB - OBJECTIVE: To analyze the outcomes of surgical treatment for severe cervicothoracic kyphosis. METHODS: A retrospective study was performed for a total of 7 patients with severe cervicothoracic kyphosis. There were congenital malformation (n = 5) and cervicothoracic tuberculosis (n = 2). The mean preoperative Cobb angle of kyphosis was 89.3 degrees (range: 72 - 103 degrees ). The average JOA (Japanese Orthopedic Association) score of neurological function was 11.2 +/- 1.2 points. Preoperative halo-pelvic traction was performed and maintained for 25 - 40 days according to the patient conditions. Then posterior instrumented fusion was performed. RESULTS: The average postoperative JOA score was 15.4 +/- 1.6 points. The mean immediate postoperative Cobb angle was 53.4 degrees (range: 45 - 67 degrees ). A mean correction rate of 40.2% was achieved. All patients were followed up for a mean of 18 months (range: 10 - 24). And a mean correction loss of 2.5 degrees was observed at the final follow-up. Two patients had transient upper limb pain during distraction. There were no intra operative or post-operative occurrences of spinal cord injury and other neurological complications. CONCLUSION: Halo-pelvic traction plus posterior spondylodesis may be a safe and effective therapy of severe cervicothoracic kyphotic deformity. PMID- 22322061 TI - [Study about outcomes of non-pharmacological conservative treatment for lumbar spinal stenosis]. AB - OBJECTIVE: To describe the short-term outcomes of a non-pharmacological conservative approach to patients with LSS. METHODS: This is a prospective consecutive case series with short-term follow-up of 21 consecutive patients who were diagnosed with LSS. Patients recruited from the outpatients of orthopaedic department and rehabilitation department in the Peking University People's Hospital from March 2010 to March 2011. Patients had baseline interviews with follow-up questionnaires in the end of the first and the third month. MAIN OUTCOME MEASURES: pain intensity was measured using the Numerical Rating Scale (NRS) and disability was measured using the Roland Morris Disability Questionnaire (RMDQ), as well as the 36-item Short Form Health Surrey (SF-36) and efficacy assessment for evaluation. RESULTS: All of 21 eligible consenting patients initially enrolling completed the follow-up. Pain at worst, functional status, quality of life improved significantly in the end of the first month. These were considered to be clinically meaningful in the end of the third month. No patients went on to require surgery. No major complications of treatment were noted. CONCLUSIONS: A non-pharmacological conservative treatment may be useful and safe in bringing about clinically meaningful improvement in pain and disability in patients with LSS. Before surgical management, a non-surgical approach should be taken into account at first. PMID- 22322062 TI - [Safety evaluation of pedicle screw placement in proximal thoracic vertebrae via funnel technique]. AB - OBJECTIVE: To evaluate the safety of funnel technique for the placement of proximal thoracic pedicle screws (T1-T5). METHODS: Between March 2006 and October 2010, 105 patients undergoing pedicle screw placement of proximal thoracic vertebrae were retrospectively reviewed. There were 57 males and 48 females with an average age of 40.3 years old. According to the techniques of placing pedicle screws, they were classified into the funnel technique group (group A, n = 54) and bare hand technique group (group B, n = 51). Their perioperative and postoperative complications were examined simultaneously. Postoperative CT (computed tomography) scans were performed in all cases to determine the instrument malposition. The percentage of malposition was analyzed between two groups and among different levels. RESULTS: A total of 402 proximal thoracic pedicle screws were placed in 105 cases. No injuries of spinal cord, large blood vessels or lung were reported. There were 13 intraoperative pedicle fractures and 4 dural tears. A total of 45 screws were misplaced in 105 patients (11.19%). In group A, the percentage of malposition was 10.14%. And there were no statistic significance among different levels (P > 0.05). In group B, the percentage of malposition was 12.31% and no statistic significance existed among different levels (P > 0.05). No intra-group statistical significance was found for group A or B. Medial malposition was found in 17 cases. And lateral malposition occurred in 25 screws while only 3 screws penetrated anterior cortex. Among 59 patients with neurological deficits, 37 cases showed postoperative improvements according to the AISA (American Spinal Injury Association) scale. CONCLUSION: The funnel technique is both safe and reliable for the placements of proximal thoracic pedicle screws. PMID- 22322063 TI - [Expressional changes of Th1 and Th2 cells in retina of a rat glaucoma model vaccinated by Cop-1]. AB - OBJECTIVE: To explore the morphological and expressional changes of Th1 cells and Th2 cells in retina of a rat model of glaucoma vaccinated by Cop-1 (Copolymer-1) and elucidate the possible neuroprotection roles played by Th1/Th2. METHODS: After modeling, the aqueous outflow from the right eyes was blocked by a ligation of three of four episcleral veins. There were 48 rats with elevated IOP (intraocular pressure) immunized by Cop-1 (Cop-1 group), 48 rats with elevated IOP immunized by PBS (phosphate-buffered saline) (PBS group) and 10 rats without any treatment (normal group). The experimental rats were immunized with Cop-1/PBS emulsified in a total volume of 0.4 ml complete Freund's adjuvant. The immunization was administered subcutaneously at the base of tail. Immunofluorescence was employed to test the distribution and activation of Th1 and Th2 cells in retina at Days 3, 7, 10, 17, 24 and 31 post-immunization respectively for each group. Western blot was selectively performed according to the results of immunofluorescence to verify if there was a similar variation of the retinal expression of IL-4 protein. RESULTS: The results of immunofluorescence showed the numbers of Th1 cells peaked at Day 7 in both Cop-1 ((216 +/- 21)/mm(2)) and PBS groups ((194 +/- 27)/mm(2)). And no statistical significance existed between two groups (P > 0.05). The numbers of Th2 cells in the experimental groups peaked at Day 7 with statistical significance (Cop-1 group: 300 +/- 28/mm(2) vs PBS group: 129 +/- 27/mm(2)) (P < 0.01). With the prolongation of experimental period, the number of Th2 cells decreased gradually in the Cop-1 group but remained greater than that of the PBS group afterward (P < 0.05). The Western blot results showed that the expression of IL-4 in the Cop-1 group (1.91 +/- 0.05) was significantly higher than that of the PBS group (0.51 +/- 0.04) from Day 3 and peaked at Day 7 (2.11 +/- 0.06 vs 0.57 +/- 0.05). Then the IL-4 expression decreased gradually in the COP-1 group but still represented statistical significance versus the PBS group until Day 31 post-immunization (P < 0.001). CONCLUSION: The retinal activation and accumulation of IL-4 are found in a rat model of chronic glaucoma immunized by Cop-1. Thus Th2 cells may play vital roles in the Cop-1-induced neuroprotective autoimmune responses. PMID- 22322064 TI - [Role of Rac1 activation in platelet derived growth factor-BB induced proliferation and migration in rat aortic smooth muscle cells]. AB - OBJECTIVE: To explore the impact of Rac1 activation on the proliferation and migration under the stimulation of PDGF-BB (platelet derived growth factor-BB). METHODS: The inhibitory effects of Rac1 inhibitor (NSC23766) and Rac1siRNA on the proliferation and migration of vascular smooth muscle cell under the stimulation of PDGF-BB were measured by CCK8 assay and Transwell chamber. The time characteristics of Rac1 activity and pi-JNK expression under the stimulation of PDGF-BB was detected by GST pulldown assay and Western blot. And the inhibitory effects of NSC23766 and Rac1siRNA on the Rac1 activation and pi-JNK expression were also measured. RESULTS: Migration and proliferation of vascular smooth muscle cell increased significantly after the stimulation of PDGF-BB (50 ug/L). Migration and proliferation was inhibited significantly after a pretreatment of Rac1siRNA and various concentrations of NSC23766 (25, 50, 100 ug/L). After the stimulation of PDGF-BB, the expression of pi-JNK and Rac1 activity increased over time. Rac1-GTP peaked at 5 minutes and pi-JNK at 15 minute. The expressions of pi JNK at 15 minutes and Rac1-GTP at 5 minutes were inhibited significantly by Rac1siRNA and NSC23766 in a concentration-dependent manner. CONCLUSION: JNK phosphorylation is controlled by Rac1 activation. And Rac1 activation play a pivotal role in the migration and proliferation of aortic smooth muscle cell under the stimulation of PDGF-BB. PMID- 22322065 TI - [Apoptosis and growth arrest of human esophageal squamous cell carcinoma cell EC9706 induced by Fufangkushen injection]. AB - OBJECTIVE: To investigate the inhibitory effect and apoptosis induction on human esophageal carcinoma EC9706 cell by Fufangkushen. METHODS: The experiment of Fufangkushen was designed into three groups including 25.00 ul/ml group, 6.25 ul/ml group and control group in vitro. The method of MTT was used to evaluate the growth inhibition effects. Proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry (IHC) in vitro. The morphological changes of cells were observed under inverted microscope. FACS was used to analyze the distribution of cell cycle and apoptosis. The expressions of Bcl-2, Fas and caspase-3 in EC9706 cells were detected by Western blotting. The clone formation in plate was used to test the capacity of cell clone formation. Nude mice experiments were conducted to investigate the tumor inhibition of Fufangkushen in vivo. The mice were divided into 3 groups of 200 ul/d treatment, 25 ul/d treatment and saline control. PCNA and Bcl-2 were detected by IHC. And the apoptotic index was detected by terminal transferase dUTP nick end labeling (TUNEL) on xenograft of nude mice. RESULTS: The proliferative capacities of 25.00 ul/ml group were lower than that of the control group at 48, 72, 96 h respectively (all P < 0.01). IHC showed the PCNA expressions, cell clone formation rate were both lower than that of control group (in 25.00 ul/ml treatment group both P < 0.05). Many apoptotic cells could be observed. And the apoptotic rate was higher in 25.00 ul/ml group than that in the control group ((25.2 +/- 7.3)% vs (3.4 +/- 1.5)%, P < 0.01). After a treatment of Fufangkushen, the activation of caspase-3 and the Fas were higher ((21.3 +/- 4.4)% vs (1.8 +/- 0.6)%, (30.2 +/- 8.3)% vs (5.4 +/- 1.6)%, both P < 0.01), the Bcl-2 were lower (P < 0.01) were observed in vitro. Comparing with the saline control group, the tumor weight in 200 ul/d treatment group were lower ((987 +/- 386) vs (1935 +/- 838) mg, P < 0.01) and the apoptotic index higher ((33.8 +/- 8.7)% vs (5.3 +/- 1.4)%, P < 0.01). CONCLUSION: Fufangkushen can inhibit the proliferation of EC9706 cells and induce the cellular apoptosis. The mechanism of apoptosis is probably associated with the arrest of cell cycle, the up-regulation of Fas, the down-regulation of Bcl-2 and the activation of caspase-3 in ESCC EC9706 cells. PMID- 22322066 TI - A fast analysis method for non-invasive imaging of blood flow in individual cerebral arteries using vessel-encoded arterial spin labelling angiography. AB - Arterial spin labelling (ASL) MRI offers a non-invasive means to create blood borne contrast in vivo for dynamic angiographic imaging. By spatial modulation of the ASL process it is possible to uniquely label individual arteries over a series of measurements, allowing each to be separately identified in the resulting angiographic images. This separation requires appropriate analysis for which a general Bayesian framework has previously been proposed. Here this framework is adapted for clinical dynamic angiographic imaging. This specifically addresses the issues of computational speed of the algorithm and the robustness required to deal with real patient data. An algorithm is proposed that can incorporate planning information about the arteries being imaged whilst adapting for subsequent patient movement. A fast maximum a posteriori solution is adopted and shown to be only marginally less accurate than Monte Carlo sampling under simulation. The final algorithm is demonstrated on in vivo data with analysis on a time scale of the order of 10min, from both a healthy control and a patient with a vertebro-basilar occlusion. PMID- 22322068 TI - Optimizing the utility of communication OSCEs: omit station-specific checklists and provide students with narrative feedback. AB - OBJECTIVE: To evaluate how the utility (reliability, validity, acceptability, feasibility, cost and educational impact) of a communication-OSCE was influenced by whether or not station-specific (StSp) checklists were used together with a generic instrument and whether or not narrative feedback was provided to students. METHODS: At ten stations, faculty members rated standardized patient student interactions using the common ground (CG) instrument (at all stations) and StSp-checklists. Both raters and patients provided written feedback. The impact of changing the design on the various utility parameters was assessed: reliability by means of a generalizability study, cost using the Reznick model and the other utility parameters by means of a survey. RESULTS: Use of the generic instrument (CG) proved more reliable (G coefficient=0.67) than using the StSp-checklists (G=0.47) or both (G=0.65) while there was a high correlation between both scale scores (Pearsons'r=0.86). The cost was 6.5% higher when StSp checklists were used and 5% higher when narrative feedback was provided. CONCLUSION: The utility of a communication OSCE can be enhanced by omitting StSp checklists and by providing narrative feedback to students. PRACTICE IMPLICATIONS: The same generic assessment scale can be used in all stations of a communication OSCE. Providing feedback to students is promising but it increases the costs. PMID- 22322067 TI - Acetyl-L-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar mitochondria without changing the L-carnitine content in the rat heart. AB - The aging heart displays a loss of bioenergetic reserve capacity partially mediated through lower fatty acid utilization. We investigated whether the age related impairment of cardiac fatty acid catabolism occurs, at least partially, through diminished levels of L-carnitine, which would adversely affect carnitine palmitoyltransferase 1 (CPT1), the rate-limiting enzyme for fatty acyl-CoA uptake into mitochondria for beta-oxidation. Old (24-28 mos) Fischer 344 rats were fed+/ acetyl-L-carnitine (ALCAR; 1.5% [w/v]) for up to four weeks prior to sacrifice and isolation of cardiac interfibrillar (IFM) and subsarcolemmal (SSM) mitochondria. IFM displayed a 28% (p<0.05) age-related loss of CPT1 activity, which correlated with a decline (41%, p<0.05) in palmitoyl-CoA-driven state 3 respiration. Interestingly, SSM had preserved enzyme function and efficiently utilized palmitate. Analysis of IFM CPT1 kinetics showed both diminished V(max) and K(m) (60% and 49% respectively, p<0.05) when palmitoyl-CoA was the substrate. However, no age-related changes in enzyme kinetics were evident with respect to L carnitine. ALCAR supplementation restored CPT1 activity in heart IFM, but not apparently through remediation of L-carnitine levels. Rather, ALCAR influenced enzyme activity over time, potentially by modulating conditions in the aging heart that ultimately affect palmitoyl-CoA binding and CPT1 kinetics. PMID- 22322069 TI - Patient and observer ratings of physician shared decision making behaviors in breast cancer consultations. AB - OBJECTIVE: Explore the validity of using patient reports to measure shared decision making (SDM). METHODS: 178 patients diagnosed with breast cancer obtained SDM assistance in a university-based clinic. Trained observers rated physician SDM behaviors and surveyed patients. We calculated the frequency with which patients and observers reported maximum SDM behaviors for each survey item. We also calculated agreement frequency between patients and observers. RESULTS: Over 90% of patients rated doctors as reflecting SDM competencies. Patients reported doctors making recommendations more than soliciting their preferred choice (90% vs. 69%, p<0.001). Patients heard benefits discussed "a lot" more often than they heard risks and side effects discussed "a lot" (81% vs. 58%, p<0.001). Agreement between patients and observers was 75%. In cases of disagreement, patients more frequently perceived SDM behaviors than did observers (15% vs. 9%, p=0.002), suggesting a possible agreement bias. CONCLUSIONS: High agreement supports further investigation into using patients as efficient and effective raters of SDM. Patient ratings may be inflated by agreement bias. PRACTICE IMPLICATIONS: Doctors presentations may be biased toward discussing benefits more than risks. Policy makers can solicit patient ratings of SDM as long as they are aware of possibly inflated ratings due to agreement bias. PMID- 22322070 TI - Synovial sarcoma in children and adolescents: a critical reappraisal of staging investigations in relation to the rate of metastatic involvement at diagnosis. AB - BACKGROUND: European protocols for paediatric synovial sarcoma (SS) require that all children routinely undergo chest computed tomography (CT) scanning and bone scanning as initial staging procedures. This study aims to determine the rate of initial metastases in paediatric SS based on specific clinical characteristics, thereby investigating whether these diagnostic procedures are really necessary in all patients. METHODS: Data on 258 previously-untreated SS patients <21 years old were pooled from the databases of different European paediatric groups (study period 1988-2005) for this analysis, and the associations between patients' characteristics and any presence of metastasis were estimated. RESULTS: Fifteen cases (5.8%) had distant metastases at diagnosis (86% pulmonary). The presence of metastases was unassociated with patients' gender or age, tumour grade or site, but it was influenced by T-status, and especially primary tumour size: the risk of metastases was 32 times higher in cases of tumour >5 cm than for tumours <= 5 cm. CONCLUSIONS: Our findings suggest that tumour diameter can be used as a variable for identifying patients at greater risk of metastases and warranting more accurate radiological investigations. Chest CT scanning may improve the accuracy of pulmonary staging over X-ray, but requires different ionising radiation exposures that might have carcinogenic potential: it can be omitted for patients with tumours <= 5 cm. Given the very low risk of bone metastases, bone scans may be recommended only in cases with evidence of lung metastases. PMID- 22322071 TI - Faculties' and nurses' perspectives regarding knowledge of high-alert medications. AB - The incorrect administration of high-alert medications can have serious consequences. A previous study by the authors of this study developed and validated 20 true-false questions concerning high-alert medications and suggested that the topic be taught to nurses. The perspectives of faculty and nurses, however, needed to be assessed before such teaching could be implemented. The aim of this study was to understand the views of faculty and nurses about training in high-alert medications: its importance, the frequency with which it is provided, and the ideal stage at which it should be provided. A cross-sectional study was conducted in 2008 in Taiwan. A questionnaire was used to determine whether the 20 questions are important, whether its content was being taught, and the ideal time for teaching it. Snowball sampling and descriptive statistics were used. A total of 136 faculty and 199 nurses participated. From the perspectives of faculty and nurses, all 20 questions regarding high-alert medications were important (faculty vs. nurses: 4.65+/-0.35 vs. 4.45+/-0.67) but the issues to which they related were insufficiently taught (faculty vs. nurses: 3.88+/-0.87 vs. 3.06+/-0.94). Faculty believed that the ideal stage at which to provide training on high-alert medications was during formal, in-school nursing education (94.3%) while nurses believed that the ideal stage was during in-hospital continuing education (48.9%). For training in high-alert medications, the researchers recommended the inclusion of classes on the subject as part of formal, in-school nursing education, as well as of hospital-based continuing education. The instrument's questions highlight the important concepts concerning high-alert medications which should be taught to nurses and nursing students. PMID- 22322072 TI - Tactile and vestibular mechanisms underlying ownership for body parts: a non visual variant of the rubber hand illusion. AB - Ownership for body parts depends on multisensory integration of visual, tactile and proprioceptive signals. In a previous study, we demonstrated that vestibular signals also contribute to ownership for body parts, since vestibular stimulation increased illusory ownership for a rubber hand. However, it remained an open question whether the vestibular information acts on the visual or on the tactile input. Here, we used a non-visual variant of the rubber hand illusion, manipulating the synchrony between tactile signals from the participant's left and right hand. The results revealed a strong illusory ownership through self reports (questionnaires) and proprioceptive drift measures. Interestingly, however, there was no influence of vestibular stimulation on illusory ownership and the proprioceptive drift. The present data suggest that vestibular signals do not interfere with the tactile-proprioceptive mechanisms underlying ownership for body parts when visual feedback from the body surface is absent. PMID- 22322074 TI - Effects of daytime, night and sleep pressure on long-term depression in the hippocampus in vivo. AB - Although long-term depression (LTD) is generally considered as one of the underlying mechanisms of learning and memory, the induction of it in vivo seems difficult. Evidence demonstrates that the total synaptic weight is associated with circadian rhythm, with up-regulation in wakefulness and down-regulation during sleep, suggesting that the induction of LTD may also be affected by it. In this study, we found that in two well-established rat models, low-frequency stimuli (LFS) induced LTD upon daytime anesthesia, but not at night. Upon further study, we found that the induction of LTD could not be blocked at night if we deprived sleep of the rats during the daytime. These results indicate that the induction of LTD is facilitated by daytime or sleep deprivation. Since rats both in the daytime and after sleep deprivation share the same character of high sleep pressure, our results suggest that LTD is actually facilitated by high sleep pressure. Our study also provides a possible explanation why some labs can induce LTD in vivo while others cannot. Sleep pressure should be taken into account as one of the key factors on the induction of LTD in vivo. PMID- 22322073 TI - Building stem cell niches from the molecule up through engineered peptide materials. AB - The native stem cell niche is a dynamic and complex microenvironment. Recapitulating this niche is a critical focus within the fields of stem cell biology, tissue engineering, and regenerative medicine and requires the development of well-defined, tunable materials. Recent biomaterial design strategies seek to create engineered matrices that interact with cells at the molecular scale and allow on-demand, cell-triggered matrix modifications. Peptide and protein engineering can accomplish these goals through the molecular-level design of bioinductive and bioresponsive materials. This brief review focuses on engineered peptide and protein materials suitable for use as in vitro neural stem cell niche mimics and in vivo central nervous system repair. A key hallmark of these materials is the immense design freedom to specify the exact amino acid sequence leading to multi-functional bulk materials with tunable properties. These advanced materials are engineered using rational design strategies to recapitulate key aspects of the native neural stem cell niche. The resulting materials often combine the advantages of biological matrices with the engineering control of synthetic polymers. Future design strategies are expected to endow these materials with multiple layers of bi-directional feedback between the cell and the matrix, which will lead to more advanced mimics of the highly dynamic neural stem cell niche. PMID- 22322075 TI - Subcortical morphological correlates of impaired clock drawing performance. AB - The objective of this study was to investigate the associations between clock drawing test (CDT) performance and subcortical brain morphology. Fifty-four participants (21 patients with Alzheimer's disease, 23 with mild cognitive impairment and 10 healthy controls) underwent neuropsychological assessment and high-resolution magnetic resonance imaging at 3T. CDT performance was related to volume and shape measurements of amygdala, caudate nucleus, hippocampus, nucleus accumbens, pallidum, putamen, and thalamus, respectively. Impaired CDT performance was correlated with alterations predominantly in the hippocampus bilaterally and in the right globus pallidus. These associations referred to regionally specific morphometric alterations rather than to global atrophy of the respective structures. Our findings support an involvement of subcortical brain regions in CDT performance. PMID- 22322076 TI - Trauma triage: right person, right place, right time. PMID- 22322078 TI - Pre-diabetes, metabolic syndrome, and cardiovascular risk. AB - Pre-diabetes represents an elevation of plasma glucose above the normal range but below that of clinical diabetes. Pre-diabetes can be identified as either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). The latter is detected by oral glucose tolerance testing. Both IFG and IGT are risk factors for type 2 diabetes, and risk is even greater when IFG and IGT occur together. Pre diabetes commonly associates with the metabolic syndrome. Both in turn are closely associated with obesity. The mechanisms whereby obesity predisposes to pre-diabetes and metabolic syndrome are incompletely understood but likely have a common metabolic soil. Insulin resistance is a common factor; systemic inflammation engendered by obesity may be another. Pre-diabetes has only a minor impact on microvascular disease; glucose-lowering drugs can delay conversion to diabetes, but whether in the long run the drug approach will delay development of microvascular disease is in dispute. To date, the drug approach to prevention of microvascular disease starting with pre-diabetes has not been evaluated. Pre diabetes carries some predictive power for macrovascular disease, but most of this association appears to be mediated through the metabolic syndrome. The preferred clinical approach to cardiovascular prevention is to treat all the metabolic risk factors. For both pre-diabetes and metabolic syndrome, the desirable approach is lifestyle intervention, especially weight reduction and physical activity. When drug therapy is contemplated and when the metabolic syndrome is present, the primary consideration is prevention of cardiovascular disease. The major targets are elevations of cholesterol and blood pressure. PMID- 22322077 TI - Hepatorenal syndrome: the 8th International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. AB - INTRODUCTION: Renal dysfunction is a common complication in patients with end stage cirrhosis. Since the original publication of the definition and diagnostic criteria for the hepatorenal syndrome (HRS), there have been major advances in our understanding of its pathogenesis. The prognosis of patients with cirrhosis who develop HRS remains poor, with a median survival without liver transplantation of less than six months. However, a number of pharmacological and other therapeutic strategies have now become available which offer the ability to prevent or treat renal dysfunction more effectively in this setting. Accordingly, we sought to review the available evidence, make recommendations and delineate key questions for future studies. METHODS: We undertook a systematic review of the literature using Medline, PubMed and Web of Science, data provided by the Scientific Registry of Transplant Recipients and the bibliographies of key reviews. We determined a list of key questions and convened a two-day consensus conference to develop summary statements via a series of alternating breakout and plenary sessions. In these sessions, we identified supporting evidence and generated recommendations and/or directions for future research. RESULTS: Of the 30 questions considered, we found inadequate evidence for the majority of questions and our recommendations were mainly based on expert opinion. There was insufficient evidence to grade three questions, but we were able to develop a consensus definition for acute kidney injury in patients with cirrhosis and provide consensus recommendations for future investigations to address key areas of uncertainty. CONCLUSIONS: Despite a paucity of sufficiently powered prospectively randomized trials, we were able to establish an evidence-based appraisal of this field and develop a set of consensus recommendations to standardize care and direct further research for patients with cirrhosis and renal dysfunction. PMID- 22322079 TI - Post-myocardial infarction cardiogenic shock is a systemic illness in need of systemic treatment: is therapeutic hypothermia one possibility? AB - Early observations of cardiogenic shock as a systemic clinical syndrome were first described in 1942. Today, cardiogenic shock remains the leading cause of death among patients hospitalized for myocardial infarction (MI). Mortality rates in post-MI cardiogenic shock approach 50% despite rapid revascularization, optimal medical care, and use of mechanical support. New therapeutic strategies with global systemic effects may offer advances in treatment and outcome in post MI cardiogenic shock. Therapeutic hypothermia for post-MI cardiogenic shock has multiple potentially beneficial physiologic effects, including the potential to improve post-ischemic cardiac function and hemodynamics, decrease myocardial damage, and reduce end-organ injury from prolonged hypoperfusion. Available data in animal models of post-MI cardiogenic shock and ischemia/reperfusion injury and small case series of human patients with cardiogenic shock suggest its promise as a potential therapeutic strategy for cardiogenic shock in the post-MI setting. We hypothesize that systemic therapeutic hypothermia could decrease morbidity and mortality in post-MI patients with cardiogenic shock and warrants study a new treatment that could be widely available at hospitals worldwide. PMID- 22322080 TI - Characteristics and long-term outcomes of percutaneous revascularization of unprotected left main coronary artery stenosis in the United States: a report from the National Cardiovascular Data Registry, 2004 to 2008. AB - OBJECTIVES: This study sought to assess percutaneous coronary intervention (PCI) for unprotected left main coronary artery (ULMCA) stenosis in routine U.S. clinical practice. BACKGROUND: Percutaneous coronary intervention for ULMCA stenosis is controversial; however, current use and outcomes of ULMCA PCI in routine U.S. clinical practice have not been described. METHODS: We evaluated 5,627 patients undergoing ULMCA PCI at 693 centers within the National Cardiovascular Data Registry Catheterization Percutaneous Coronary Intervention Registry for temporal trends in PCI use (2004 to 2008), patient characteristics, and in-hospital mortality. Thirty-month mortality and composite major adverse events (death, myocardial infarction, and revascularization) with drug-eluting versus bare-metal stents were compared using inverse probability weighted (IPW) hazard ratios (HRs) in a nonrandomized Medicare-linked (age >=65 years) patient cohort (n = 2,765). RESULTS: ULMCA PCI was performed in 4.3% of patients with ULMCA stenosis. Unadjusted in-hospital mortality rates ranged from 2.9% for elective cases to 45.1% for emergent/salvage cases. By 30 months, 57.9% of the elderly ULMCA PCI population experienced death, myocardial infarction, or revascularization, and 42.7% died. Patients receiving drug-eluting stents (versus bare-metal stents) had a lower 30-month mortality (IPW HR: 0.84, 95% confidence interval [CI]: 0.73 to 0.96), but the composite of major adverse events were similar (IPW HR: 0.95, 95% CI: 0.84 to 1.06). CONCLUSIONS: In the United States, ULMCA PCI is performed in <5% of patients with ULMCA disease and is generally reserved for those at high procedural risk. Adverse events are common in elderly patients and are related to patient and procedural characteristics, including stent type. PMID- 22322081 TI - High prevalence of a pathological response to acetylcholine testing in patients with stable angina pectoris and unobstructed coronary arteries. The ACOVA Study (Abnormal COronary VAsomotion in patients with stable angina and unobstructed coronary arteries). AB - OBJECTIVES: This study aimed at determining the prevalence of epicardial and microvascular coronary spasm in patients with anginal symptoms, despite angiographically normal coronary arteries. BACKGROUND: Despite a typical clinical presentation with exercise-related anginal symptoms (chest pain or dyspnea) with or without occasional attacks of resting chest pain suggestive of coronary artery disease, 40% of patients undergoing diagnostic angiography have normal or "near" normal coronary arteriograms. Many of these patients are given a diagnosis of noncardiac chest pain, and some are considered to have microvascular angina. However, we speculate that abnormal coronary vasomotion (reduced vasodilatation with exercise = reduced coronary flow reserve and/or vasospasm at rest) might also represent a plausible explanation for the symptoms of the patient. METHODS: This was a prospective study in 304 consecutive patients (50% men, mean age 66 +/ 10 years) with exertional anginal symptoms undergoing diagnostic angiography. A total of 139 patients (46%) had >=50% coronary artery disease in at least 1 coronary artery, 21 patients (7%) had luminal narrowings ranging from >20% to 49%, and 144 patients (47%) had normal coronary arteries or only minimal irregularities (<20% diameter reduction). RESULTS: One hundred twenty-four patients of the latter (86%) underwent intracoronary acetylcholine (ACH) testing, which elicited coronary spasm in 77 patients (62%), 35 patients (45%) with epicardial spasm (>=75% diameter reduction with reproduction of the symptoms of the patient) and 42 patients (55%) with microvascular spasm (reproduction of symptoms, ischemic electrocardiographic changes, and no epicardial spasm). CONCLUSIONS: Nearly 50% of patients undergoing diagnostic angiography for assessment of stable angina had angiographically normal or near normal coronary arteriograms. The ACH test triggered epicardial or microvascular coronary spasm in nearly two-thirds of these patients. Our results suggest that abnormal coronary vasomotion plays a pathogenic role in this setting and that the ACH test might be useful to identify patients with cardiac symptoms, despite normal coronaries. (Abnormal Coronary Vasomotion in Patients With Suspected CAD But Normal Coronary Arteries; NCT00921856). PMID- 22322082 TI - Coronary vasospasm and coronary atherosclerosis: do we have to choose? PMID- 22322083 TI - Changes in fitness and fatness on the development of cardiovascular disease risk factors hypertension, metabolic syndrome, and hypercholesterolemia. AB - OBJECTIVES: This study sought examine the independent and combined associations of changes in fitness and fatness with the subsequent incidence of the cardiovascular disease (CVD) risk factors of hypertension, metabolic syndrome, and hypercholesterolemia. BACKGROUND: The relative and combined contributions of fitness and fatness to health are controversial, and few studies are available on the associations of changes in fitness and fatness with the development of CVD risk factors. METHODS: We followed up 3,148 healthy adults who received at least 3 medical examinations. Fitness was determined by using a maximal treadmill test. Fatness was expressed by percent body fat and body mass index. Changes in fitness and fatness between the first and second examinations were categorized into loss, stable, or gain groups. RESULTS: During the 6-year follow-up after the second examination, 752, 426, and 597 adults developed hypertension, metabolic syndrome, and hypercholesterolemia, respectively. Maintaining or improving fitness was associated with lower risk of developing each outcome, whereas increasing fatness was associated with higher risk of developing each outcome, after adjusting for possible confounders and fatness or fitness for each other (all p for trend <0.05). In the joint analyses, the increased risks associated with fat gain appeared to be attenuated, although not completely eliminated, when fitness was maintained or improved. In addition, the increased risks associated with fitness loss were also somewhat attenuated when fatness was reduced. CONCLUSIONS: Both maintaining or improving fitness and preventing fat gain are important to reduce the risk of developing CVD risk factors in healthy adults. PMID- 22322084 TI - Left atrial function predicts heart failure hospitalization in subjects with preserved ejection fraction and coronary heart disease: longitudinal data from the Heart and Soul Study. AB - OBJECTIVES: This study sought to determine whether left atrial (LA) dysfunction predicts heart failure (HF) hospitalization in subjects with preserved baseline ejection fraction (EF). BACKGROUND: Among patients with preserved EF, factors leading to HF are not fully understood. Cross-sectional studies have demonstrated LA dysfunction at the time of HF, but longitudinal data on antecedent atrial function are lacking. METHODS: We performed resting transthoracic echocardiography in 855 subjects with coronary heart disease and EF >=50%. Left atrial functional index (LAFI) was calculated as ([LA emptying fraction * left ventricular outflow tract-velocity time integral] / [indexed LA end-systolic volume]), where LA emptying fraction was defined as (LA end-systolic volume--LA end-diastolic volume) / LA end-systolic volume. We used Cox models to evaluate the association between LAFI and HF hospitalization. RESULTS: Over a median follow-up of 7.9 years, 106 participants (12.4%) were hospitalized for HF. Rates of HF hospitalization were inversely proportional to quartile (Q) of LAFI: Q1, 47 per 1,000 person-years; Q2, 18.3; Q3, 9.6; and Q4, 5.3 (p < 0.001). Each standard deviation decrease in LAFI was associated with a 2.6-fold increased hazard of adverse cardiovascular outcomes (unadjusted hazard ratio: 2.6, 95% confidence interval: 2.1 to 3.3, p < 0.001), and the association persisted even after adjustment for clinical risk factors, N-terminal pro-B-type natriuretic peptide, and a wide range of echocardiographic parameters (adjusted hazard ratio: 1.5, 95% confidence interval: 1.0 to 2.1, p = 0.05). CONCLUSIONS: Left atrial dysfunction independently predicts HF hospitalization in subjects with coronary heart disease and preserved baseline EF. The LAFI may be useful for HF risk stratification, and LA dysfunction may be a potential therapeutic target. PMID- 22322085 TI - Timing of the most recent device procedure influences the clinical outcome of lead-associated endocarditis results of the MEDIC (Multicenter Electrophysiologic Device Infection Cohort). AB - OBJECTIVES: The purpose of this study was to determine whether the timing of the most recent cardiac implantable electronic device (CIED) procedure, either a permanent pacemaker or implantable cardioverter-defibrillator, influences the clinical presentation and outcome of lead-associated endocarditis (LAE). BACKGROUND: The CIED infection rate has increased at a time of increased device use. LAE is associated with significant morbidity and mortality. METHODS: The clinical presentation and course of LAE were evaluated by the MEDIC (Multicenter Electrophysiologic Device Cohort) registry, an international registry enrolling patients with CIED infection. Consecutive LAE patients enrolled in the Multicenter Electrophysiologic Device Cohort registry between January 2009 and May 2011 were analyzed. The clinical features and outcomes of 2 groups were compared based on the time from the most recent CIED procedure (early, <6 months; late, >6 months). RESULTS: The Multicenter Electrophysiologic Device Cohort registry entered 145 patients with LAE (early = 43, late = 102). Early LAE patients presented with signs and symptoms of local pocket infection, whereas a remote source of bacteremia was present in 38% of patients with late LAE but only 8% of early LAE (p < 0.01). Staphylococcal species were the most frequent pathogens in both early and late LAE. Treatment consisted of removal of all hardware and intravenous administration of antibiotics. In-hospital mortality was low (early = 7%, late = 6%). CONCLUSIONS: The clinical presentation of LAE is influenced by the time from the most recent CIED procedure. Although clinical manifestations of pocket infection are present in the majority of patients with early LAE, late LAE should be considered in any CIED patient who presents with fever, bloodstream infection, or signs of sepsis, even if the device pocket appears uninfected. Prompt recognition and management may improve outcomes. PMID- 22322086 TI - Coronary computed tomography angiography after stress testing: results from a multicenter, statewide registry, ACIC (Advanced Cardiovascular Imaging Consortium). AB - OBJECTIVES: This study was conducted to evaluate the correlation between stress test results and coronary computed tomography angiography (CCTA) findings and comparative diagnostic performance of the 2 modalities in patients undergoing invasive coronary angiography (ICA). BACKGROUND: Recent data suggest that only a third of patients undergoing ICA have obstructive coronary artery disease (CAD); accurate pre-ICA risk stratification is needed. METHODS: At 47 centers participating in the ACIC (Advanced Cardiovascular Imaging Consortium) in Michigan, patients without known CAD who were undergoing CCTA within 3 months of a stress test were studied. Demographics, risk factors, symptoms, and stress test results were correlated with obstructive CAD (>50% stenosis) on CCTA and ICA. RESULTS: Among 6,198 patients (age 56 +/- 12 years, 48% men), >50% stenosis was seen in 1,158 (18.7%) on CCTA. Independent predictors included male sex (odds ratio [OR]: 2.37, 95% confidence interval [CI]: 1.83 to 3.06), current smoking (OR: 2.23, 95% CI: 1.57 to 3.17), older age (OR per 10-year increment: 2.14, 95% CI: 1.89 to 2.41), hypertension (OR: 1.8, 95% CI: 1.37 to 2.34), and typical angina (OR: 1.48, 95% CI: 1.03 to 2.12). Stress test results were not predictive. Among patients undergoing ICA (n = 621), there was a strong correlation of ICA with CCTA findings (OR: 9.09, 95% CI: 5.57 to 14.8, p < 0.001), but not stress results (OR: 0.79, 95% CI: 0.56 to 1.11, p = 0.17). CONCLUSIONS: Stress test findings did not predict obstructive CAD on CCTA, observed in <20% of patients in this large study group. The strong association of CCTA with ICA suggests that it may serve as an effective "gatekeeper" to invasive testing in patients needing adjudication of stress test results. (Advanced Cardiovascular Imaging Consortium: A Collaborative Quality Improvement Project [ACIC]; NCT00640068). PMID- 22322087 TI - Computed tomography coronary angiography: a noninvasive escape when stress tests fail (caught between guidelines and gut feeling). PMID- 22322088 TI - Shone's complex and levoatriocardinal vein: a rare association. PMID- 22322089 TI - Carotid intima-medial thickness in National Football League players as an index of cardiovascular disease risk. PMID- 22322090 TI - Coronary computed tomography angiography versus coronary calcium computed tomography for prognosis with regard to mortality. PMID- 22322092 TI - Polyarteritis nodosa involving renal and coronary arteries. PMID- 22322093 TI - Mortality associated with traumatic injuries in the elderly: a population based study. AB - Elderly trauma is increasing in incidence and is associated with significant morbidity and mortality. The primary objective of the study was to identify factors associated with survival or mortality in the elderly following trauma. The secondary objective was to compare the epidemiology of trauma in the elderly with younger patients. A retrospective analysis was performed of data that was obtained from a prospectively collected multi-centre trauma database maintained by The Scottish Trauma Audit Group (STAG) containing details of 52,887 trauma patients admitted to 25 participating Scottish Hospitals over an 11-year period. Elderly trauma patients (aged >80 years) were separately analyzed and compared to younger trauma patients (aged 13-80). Of 52,887 trauma patients identified, 4791 were elderly (9.1%). Elderly patients had a higher absolute mortality rate following traumatic injury (9.9% versus 4%, p<0.001). Mortality in the elderly was higher in males, following a high fall, with lower Glasgow Coma Scale (GCS), in those with higher Abbreviated Injury Scale (AIS)/Injury Severity Score (ISS), in those with concomitant injuries, hemodynamic compromise and following delayed presentation. Multiple logistic regression analysis confirmed an independent relationship between mortality and low GCS, male gender, higher ISS, higher AIS of spinal injury, hemodynamic compromise and concomitant minor leg/arm injury(ies) in the elderly. In conclusion, trauma in elderly patients is associated with significantly higher mortality. Low GCS, male gender, higher ISS, higher AIS of spinal injury, hemodynamic compromise and concomitant minor leg/arm injury(ies) have the strongest independent relationships with mortality after trauma in the elderly population. PMID- 22322094 TI - Micronutrient (Zn, Cu, Fe)-gene interactions in ageing and inflammatory age related diseases: implications for treatments. AB - In ageing, alterations in inflammatory/immune response and antioxidant capacity lead to increased susceptibility to diseases and loss of mobility and agility. Various essential micronutrients in the diet are involved in age-altered biological functions. Micronutrients (zinc, copper, iron) play a pivotal role either in maintaining and reinforcing the immune and antioxidant performances or in affecting the complex network of genes (nutrigenomic approach) involved in encoding proteins for a correct inflammatory/immune response. By the other side, the genetic inter-individual variability may affect the absorption and uptake of the micronutrients (nutrigenetic approach) with subsequent altered effects on inflammatory/immune response and antioxidant activity. Therefore, the individual micronutrient-gene interactions are fundamental to achieve healthy ageing. In this review, we report and discuss the role of micronutrients (Zn, Cu, Fe)-gene interactions in relation to the inflammatory status and the possibility of a supplement in the event of a micronutrient deficiency or chelation in presence of micronutrient overload in relation to specific polymorphisms of inflammatory proteins or proteins related of the delivery of the micronutriemts to various organs and tissues. In this last context, we report the protein-metal speciation analysis in order to have, coupled with micronutrient-gene interactions, a more complete picture of the individual need in micronutrient supplementation or chelation to achieve healthy ageing and longevity. PMID- 22322095 TI - The human respiratory syncytial virus nonstructural protein 1 regulates type I and type II interferon pathways. AB - Respiratory syncytial viruses encode a nonstructural protein (NS1) that interferes with type I and III interferon and other antiviral responses. Proteomic studies were conducted on human A549 type II alveolar epithelial cells and type I interferon-deficient Vero cells (African green monkey kidney cells) infected with wild-type and NS1-deficient clones of human respiratory syncytial virus to identify other potential pathway and molecular targets of NS1 interference. These analyses included two-dimensional differential gel electrophoresis and quantitative Western blotting. Surprisingly, NS1 was found to suppress the induction of manganese superoxide dismutase (SOD2) expression in A549 cells and to a much lesser degree Vero cells in response to infection. Because SOD2 is not directly inducible by type I interferons, it served as a marker to probe the impact of NS1 on signaling of other cytokines known to induce SOD2 expression and/or indirect effects of type I interferon signaling. Deductive analysis of results obtained from cell infection and cytokine stimulation studies indicated that interferon-gamma signaling was a potential target of NS1, possibly as a result of modulation of STAT1 levels. However, this was not sufficient to explain the magnitude of the impact of NS1 on SOD2 induction in A549 cells. Vero cell infection experiments indicated that NS1 targeted a component of the type I interferon response that does not directly induce SOD2 expression but is required to induce another initiator of SOD2 expression. STAT2 was ruled out as a target of NS1 interference using quantitative Western blot analysis of infected A549 cells, but data were obtained to indicate that STAT1 was one of a number of potential targets of NS1. A label-free mass spectrometry-based quantitative approach is proposed as a means of more definitive identification of NS1 targets. PMID- 22322096 TI - PTMScan direct: identification and quantification of peptides from critical signaling proteins by immunoaffinity enrichment coupled with LC-MS/MS. AB - Proteomic studies of post-translational modifications by metal affinity or antibody-based methods often employ data-dependent analysis, providing rich data sets that consist of randomly sampled identified peptides because of the dynamic response of the mass spectrometer. This can complicate the primary goal of programs for drug development, mutational analysis, and kinase profiling studies, which is to monitor how multiple nodes of known, critical signaling pathways are affected by a variety of treatment conditions. Cell Signaling Technology has developed an immunoaffinity-based LC-MS/MS method called PTMScan Direct for multiplexed analysis of these important signaling proteins. PTMScan Direct enables the identification and quantification of hundreds of peptides derived from specific proteins in signaling pathways or specific protein types. Cell lines, tissues, or xenografts can be used as starting material. PTMScan Direct is compatible with both SILAC and label-free quantification. Current PTMScan Direct reagents target key nodes of many signaling pathways (PTMScan Direct: Multipathway), serine/threonine kinases, tyrosine kinases, and the Akt/PI3K pathway. Validation of each reagent includes score filtering of MS/MS assignments, filtering by identification of peptides derived from expected targets, identification of peptides homologous to expected targets, minimum signal intensity of peptide ions, and dependence upon the presence of the reagent itself compared with a negative control. The Multipathway reagent was used to study sensitivity of human cancer cell lines to receptor tyrosine kinase inhibitors and showed consistent results with previously published studies. The Ser/Thr kinase reagent was used to compare relative levels of kinase-derived phosphopeptides in mouse liver, brain, and embryo, showing tissue-specific activity of many kinases including Akt and PKC family members. PTMScan Direct will be a powerful quantitative method for elucidation of changes in signaling in a wide array of experimental systems, combining the specificity of traditional biochemical methods with the high number of data points and dynamic range of proteomic methods. PMID- 22322097 TI - A bipolar spin-filtering effect in graphene zigzag nanoribbons with spin-orbit coupling. AB - We predict a large spin-filtering effect in graphene zigzag nanoribbons in the presence of Rashba spin-orbit coupling. The spin polarization of the transmitted current reaches a maximum when the incoming electrons occupy only one subband and the outgoing electrons occupy two subbands (spin is not taken into account). This situation can be reached by applying a potential barrier or a width constriction to the incoming lead of the ribbon. A simple physical picture is provided to explain the spin-filtering effect. Because of the electron-hole symmetry and the time-reversal symmetry, the spin-filtering is antisymmetric for the hole when compared with that for the electron. So the bipolar spin-polarized current can be generated by tuning the Fermi energy across the Dirac point. Besides, the wedge shaped constriction can modify the conductance spin polarization. PMID- 22322099 TI - Consumer-directed health plans with health savings accounts: whose skin is in the game and how do costs affect care seeking? AB - BACKGROUND: Employers are increasingly offering high-deductible health insurance plans with associated health savings accounts (HSAs), but there is limited information on account contributions or effects on patient care seeking. OBJECTIVE: We examined HSA contributions and their source, patient-reported effects of costs on care seeking, and reports of financial burden. RESEARCH DESIGN: We conducted telephone interviews with 488 adult members of small group of employer-sponsored HSA-eligible plans within an integrated delivery system. PRINCIPAL FINDINGS: HSA contribution sources and amounts varied with 32% receiving an employer contribution and also making their own employee contribution, 35% only receiving an employer contribution (no employee contribution), 19% only making their own contribution (no employer contribution), and 14% with no HSA contribution from either source. After adjustment for respondent characteristics, those who made their own HSA contributions in addition to their employer's contribution were significantly more likely to report that costs affected their care-seeking behavior, compared with those with only employer contributions (39% vs. 31% for emergency department and 60% vs. 49% for office visits, all P<0.05). Respondents who contributed to their HSA or who paid out-of-pocket for care were significantly more likely to report financial burdens than those with only employer contributions (P<0.05). CONCLUSIONS: The majority of consumers receive employer contributions to their HSA, but few have fully funded accounts. Those with only an employer contribution reported fewer changes in their care-seeking behavior and were less likely to report experiencing financial burdens. PMID- 22322098 TI - Safety and tolerability of repetitive transcranial magnetic stimulation in patients with pathologic positive sensory phenomena: a review of literature. AB - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is emerging as a valuable therapeutic and diagnostic tool. rTMS appears particularly promising for disorders characterized by positive sensory phenomena that are attributable to alterations in sensory cortical excitability. Among these are tinnitus, auditory and visual hallucinations, and pain syndromes. OBJECTIVE: Despite studies addressing rTMS efficacy in suppression of positive sensory symptoms, the safety of stimulation of potentially hyperexcitable cortex has not been fully addressed. We performed a systematic literature review and metaanalysis to describe the rTMS safety profile in these disorders. METHODS: Using the PubMed database, we performed an English-language literature search from January 1985 to April 2011 to review all pertinent publications. Per study, we noted and listed pertinent details. From these data we also calculated a crude per-subject risk for each adverse event. RESULTS: One hundred six publications (n = 1815) were identified with patients undergoing rTMS for pathologic positive sensory phenomena. Adverse events associated with rTMS were generally mild and occurred in 16.7% of subjects. Seizure was the most serious adverse event, and occurred in three patients with a 0.16% crude per-subject risk. The second most severe adverse event involved aggravation of sensory phenomena, occurring in 1.54%. CONCLUSIONS: The published data suggest rTMS for the treatment or diagnosis of pathologic positive sensory phenomena appears to be a relatively safe and well-tolerated procedure. However, published data are lacking in systematic reporting of adverse events, and safety risks of rTMS in these patient populations will have to be addressed in future prospective trials. PMID- 22322100 TI - Designing and implementing research on a statewide quality improvement initiative: the DIAMOND study and initiative. AB - OBJECTIVE: To demonstrate a rigorous methodology that optimally balanced internal validity with generalizability to evaluate a statewide collaborative that implemented an evidence-based, collaborative care model for depression management in primary care. STUDY DESIGN AND SETTING: Several operational features of the DIAMOND (Depression Improvement Across Minnesota, Offering a New Direction) Initiative suggested that the DIAMOND Study use a staggered implementation design with repeated cross-sections of patients across clinical settings. A multilevel recruitment strategy elicited virtually complete study participation from the medical groups, clinics, and health plans that coordinated efforts to deliver and reimburse DIAMOND care. Patient identification capitalized on large health plan claims databases to rapidly identify the population of patients newly treated for depression in DIAMOND clinics. RESULTS: The staggered implementation design and multilevel recruitment strategy made it possible to evaluate DIAMOND by holding confounding factors constant and accurately identifying an intent-to-treat population of patients treated for depression without intruding on or requiring effort from their clinics. CONCLUSIONS: Recruitment and data collection from health plans, medical groups and clinics, and patients ensured a representative, intent-to-treat sample of study-enrolled patients. Separating patient identification from care delivery reduced threats of selection bias and enabled comparisons between the treated population and study sample. A key challenge is that intent-to-treat patients may not be exposed to DIAMOND which dilutes the effect size but offers realistic expectations of the impact of quality improvement in a population of treated patients. PMID- 22322101 TI - Deregulation of nonprescription medicines in Sweden-a look at the control system. AB - BACKGROUND: Sales of nonprescription medicines (NPMs) in retail outlets in Sweden have been permitted since 2009. The conditions are that sales are reported to the Medicine Product Agency (MPA) and that the owners of the retail outlets fulfill legal requirements. The MPA has an overall supervisory function, whereas municipalities are responsible for the actual control. This is mainly executed through inspections. OBJECTIVE: The aim of the study was to explore some aspects of control performed by Swedish authorities of NPM sales in retail outlets. METHODS: Telephonic interviews were conducted with inspectors from a heterogenic sample of municipalities in Sweden during autumn of 2010. A semistructured interview guide was designed, which included questions on inspections and deviations found in inspections. Interviews were documented in writing, and a deductive content analysis was performed. RESULTS: Inspectors in 15 municipalities participated. In 8 of the municipalities, at least 1 inspection had been conducted. Seven inspectors had used a checklist designed by the MPA, although a majority found it difficult to use. Deviations found were mainly minor; they included lack of signs regarding age limits and prohibition of illegal sales, unlocked/open drug cabinet doors, nonexistent self-inspection programs, erroneous display of NPMs, and broken drug packages. Two serious deviations were found and reported to the MPA; these were negligence in reporting of sales statistics of NPM and 1 case where the inspector had not been allowed to conduct any inspection. CONCLUSION: The restructuring of the sale of NPMs in Sweden, permitting sale outside pharmacies, has not been accompanied by satisfactory control procedures from authorities according to our findings. Work is still needed to make sure that optimal drug use and patient safety issues are kept in focus. PMID- 22322102 TI - Prevalence of diabetic neuropathy in patients undergoing foot and ankle surgery. AB - INTRODUCTION: The aim of this prospective study was to determine the prevalence of neuropathy in diabetic patients undergoing foot and ankle surgery. It was hypothesized that the prevalence of diabetic neuropathy is higher among patients who undergo foot and ankle surgery compared with historical rates of neuropathy in diabetic patients in general. METHODS: During a consecutive 42-month period, patient data were prospectively entered for 1859 consecutive patients undergoing foot and ankle surgery. Among the subjects, 394 had been previously diagnosed with diabetes mellitus (DM), and the remaining 1465 did not have DM. RESULTS: The prevalence of neuropathy in patients with and without DM was 77.2% (304 of 394 patients) and 11.7% (172 of 1465 patients), respectively. Patients with diabetic neuropathy were older, had poorer glycemic control, had higher serum creatinine levels, and reported more significant tobacco use than diabetic patients without neuropathy. CONCLUSION: Nearly 80% of diabetic patients undergoing foot and ankle surgery at a large academic medical center had diabetic neuropathy. Preoperative recognition of this morbid complication of DM is important to appropriately stratify those diabetic patients into a high-risk category. PMID- 22322103 TI - Arthroscopic reduction and fibula nailing in high-risk diabetic ankle fractures: case reviews and technical tip. AB - The management of diabetic ankle fractures is difficult given the associated wound and bone healing complications. Even with meticulous soft tissue handling and a stable construct, the fixation sometimes fails because of the poor biological environment. This study reports on 2 cases of Weber type B ankle fractures in patients with diabetes mellitus where the authors elected to treat with arthroscopy-assisted fracture reduction and percutaneous fibula nailing to reduce the risk of wound complications. PMID- 22322104 TI - Potential utility of optogenetics in the study of depression. AB - Novel antidepressants are needed to enhance the health and quality of life of the hundreds of millions of depressed individuals worldwide who remain inadequately treated with today's approaches. In reality, no new class of antidepressant medication has been introduced in over 50 years. This insufficiency of current drug treatments is evident to those eager to pursue invasive experimental options like that of deep brain stimulation. Encouragingly, human brain imaging studies and animal work implicate strong relationships between depressive symptoms and patterns of brain activity, which are now open to more empirical assessments using optogenetics. Recent advances in optogenetics permit control over specific subtypes of neurons or their afferent or efferent projections and can greatly further our understanding of the neural mechanisms involved in depression and the mechanism of action of deep brain stimulation and perhaps chemical antidepressants. Here, we discuss how optogenetic tools are being used to answer a broad range of molecular, cellular, and circuit-level questions pertaining to depression that, up until now, have been resistant to other experimental approaches. The emergence of optogenetic technology, when combined with the best validated animal models of depression, will dramatically increase knowledge about the basic neurobiology of depression, as well as facilitate the development of more effective antidepressant treatments. PMID- 22322105 TI - Depressive symptoms in mild cognitive impairment predict greater atrophy in Alzheimer's disease-related regions. AB - BACKGROUND: Depression has been associated with higher conversion rates from mild cognitive impairment (MCI) to Alzheimer's disease (AD) and may be a marker of prodromal AD that can be used to identify individuals with MCI who are most likely to progress to AD. Thus, we examined the neuroanatomical changes associated with depressive symptoms in MCI. METHODS: Two-hundred forty-three MCI subjects from the Alzheimer's Disease Neuroimaging Initiative who had brain magnetic resonance imaging scans at baseline and 2-year follow-up were classified into depressed (n = 44), nondepressed with other neuropsychiatric symptoms (n = 93), and no-symptom (NOSYMP; n = 106) groups based on the Neuropsychiatric Inventory Questionnaire. Tensor-based morphometry was used to create individual three-dimensional maps of 2-year brain changes that were compared between groups. RESULTS: Depressed subjects had more frontal (p = .024), parietal (p = .030), and temporal (p = .038) white matter atrophy than NOSYMP subjects. Those whose depressive symptoms persisted over 2 years also had higher conversion to AD and more decline on measures of global cognition, language, and executive functioning compared with stable NOSYMP subjects. Nondepressed with other neuropsychiatric symptoms and NOSYMP groups exhibited no differences in rates of atrophy. CONCLUSIONS: Depressive symptoms were associated with greater atrophy in AD affected regions, increased cognitive decline, and higher rates of conversion to AD. Depression in individuals with MCI may be associated with underlying neuropathological changes, including prodromal AD, and may be a potentially useful clinical marker in identifying MCI patients who are most likely to progress to AD. PMID- 22322106 TI - Evaluation of optimum room entry times for radiation therapists after high energy whole pelvic photon treatments. AB - OBJECTIVES: Linear accelerators operating at or above 10 MV produce neutrons by photonuclear reactions and induce activation in machine components, which are a source of potential exposure for radiation therapists. This study estimated gamma dose contributions to radiation therapists during high energy, whole pelvic, photon beam treatments and determined the optimum room entry times, in terms of safety of radiation therapists. METHODS: Two types of technique (anterior posterior opposing and 3-field technique) were studied. An Elekta Precise treatment system, operating up to 18 MV, was investigated. Measurements with an area monitoring device (a Mini 900R radiation monitor) were performed, to calculate gamma dose rates around the radiotherapy facility. Measurements inside the treatment room were performed when the linear accelerator was in use. The doses received by radiation therapists were estimated, and optimum room entry times were determined. RESULTS: The highest gamma dose rates were approximately 7 MUSv/h inside the treatment room, while the doses in the control room were close to background (~0 MUSv/h) for all techniques. The highest personal dose received by radiation therapists was estimated at 5 mSv/yr. To optimize protection, radiation therapists should wait for up to11 min after beam-off prior to room entry. CONCLUSIONS: The potential risks to radiation therapists with standard safety procedures were well below internationally recommended values, but risks could be further decreased by delaying room entry times. Dependent on the technique used, optimum entry times ranged between 7 to 11 min. A balance between moderate treatment times versus reduction in measured equivalent doses should be considered. PMID- 22322107 TI - Health disparities among occupations in Taiwan: a population study. AB - OBJECTIVES: The first large-scale population survey was conducted in Taiwan to examine if and to what extent health disparities of four major chronic physical conditions exist among occupations. METHODS: Face-to-face interviews about two risk behaviors (i.e., cigarette and alcohol use) and four major chronic physical conditions (i.e., cardiovascular disease, diabetes, liver disease and asthma) were conducted with 13,741 workers from nine major categories of occupations. RESULTS: Health disparities among occupations were found based on a series of hierarchical logistic regression analyses after controlling for age, sex and two risk behaviors. In general, prevalence rates of cardiovascular disease among elementary occupations and skilled agricultural and fishery workers were approximately two to four times higher than those among other occupations. The above two occupations and plant and machine operators also had higher prevalence rates in diabetes and liver disease. CONCLUSIONS: The results concerning health disparities among occupations provide policymakers and researchers with invaluable benchmarks of chronic physical conditions among occupations. The findings also suggest the importance of investigating causal relationship between these diseases and exposures at work, identifying and reducing unique risk factors and hazard exposures experienced by workers and conducting targeted surveillance and health promotion programs for at-risk occupations. PMID- 22322108 TI - Assessment of workplace air concentrations of indium dust in an indium-recycling plant. AB - OBJECTIVES: Suspended indium dust in an indium-recycling plant was quantified, in order to improve the work environment and to reduce workers' exposure to the dust. METHODS: Assessment of indium dust in the workplace air by multipoint area sampling and personal breathing zone sampling was conducted twice in 2004 and 2008. RESULTS: In 2004, all recycling processes except for purity analysis were classified into control class III according to the 2004 Notification. Two out of 5 workers were exposed to total dust with indium concentrations exceeding the ACGIH's TLV-TWA of 0.1 mg In/m(3). In 2008, the indium-contaminated workplace air was improved by local exhaust ventilation systems installed in some processes, resulting in control class I. According to the 2010 Technical Guideline, however, all the processes were classified into stage II or III, indicating that the first assessment value or Measurement B-based concentrations exceeded the acceptable exposure concentration limit of 0.0003 mg In/m(3) of respirabe dust. Exposure of almost all the workers to indium dust was below the TLV-TWA. CONCLUSIONS: The first field survey showed that almost all workplaces were classified into control class III, and that some workers were exposed to dust with indium concentrations exceeding the TLV-TWA. It was found in the second survey that workplace air contamination was improved by the local exhaust ventilation system, but was not reduced sufficiently to a level that meets the new Guideline. PMID- 22322110 TI - The influence of lens power and center thickness on the intraocular pressure measured through soft lenses: a comparison of two noncontact tonometers. AB - PURPOSE: To quantify the influence of soft contact lens power and thickness on the intraocular pressure (IOP). METHODS: Thirty-nine young, healthy adult volunteers completed this study. One eye of each subject was randomly assigned either a +6D or a -6D high water content daily disposable lens. The other eye was fitted with the second lens. Triplicate measurements of IOP were taken before, during, and after contact lens wear. Each time, IOP was assessed in a randomized order with two noncontact tonometers. The lenses were swapped between eyes during a second session of measurements, one week later. RESULTS: In the first session with the +6D lenses, the average IOPs (+/-SDs) before, with the lenses fitted, and after the lenses were removed, were: 14.3 +/- 2.9 mmHg, 17.0 +/- 3.3 mmHg and 13.9 +/- 3.1 mmHg, respectively, for the CT80 and 13.6 +/- 3.1 mmHg, 17.1 +/- 4.5 mmHg and 13.3 +/- 2.9 mmHg, respectively, for the PT100. The corresponding values for the first session with the -6D lenses were: 14.3 +/- 3.1 mmHg, 13.1 +/- 3.1 mmHg and 14.1 +/- 3.3 mmHg, respectively, for the CT80 and 13.6 +/- 3.2 mmHg, 13.0 +/- 3.0 mmHg and 13.6 +/- 3.2 mmHg, respectively, for the PT100. IOP significantly (P<0.05) increased (+DeltaIOP=2.7 +/- 0.4 mmHg with the CT80 in the first session) with the +6D lenses, but decreased (P<0.05) when the -6D lenses were fitted (-DeltaIOP=0.6 +/- 0.2 mmHg with the PT100 in the first session). The soft contact lens-induced changes were consistent between sessions but varied between tonometers. CONCLUSIONS: The measurement of IOP through soft contact lenses resulted in consistent, statistically significant differences in IOP, which were not uniform across tonometers and which did not appear to be solely related to the central thickness of the soft contact lenses. PMID- 22322111 TI - Glucans of Pleurotus florida blue variant: isolation, purification, characterization and immunological studies. AB - Two different glucans (PS-I and PS-II) were isolated from the alkaline extract of the fruiting bodies of an edible mushroom, Pleurotus florida blue variant and the PS-I showed macrophage, splenocyte and thymocyte activations. On the basis of sugar analysis, methylation analysis, periodate oxidation, and NMR studies ((1)H, (13)C, DEPT-135, DQF-COSY, TOCSY, NOESY, ROESY, HMQC and HMBC), the structure of the repeating unit of these polysaccharides were established. PMID- 22322112 TI - Synthesis and property of chitosan graft copolymer by RAFT polymerization with tosylic acid-chitosan complex. AB - pH- and thermo-sensitive (1->4)-2-amino-2-deoxy-beta-d-glucan (i.e. chitosan) graft copolymer was prepared by reversible addition fragmentation chain transfer polymerizations of N-isopropylacrylamide with 4-methylbenzenesulfonic acid (i.e. tosylic acid)-chitosan complex. The polymerization was controlled well, and the amino group of chitosan could be deprotected easily and mildly with 15% Tris solution. The model aldehyde vanillin was conjugated with amino group of chitosan g-PNIPAM via Schiff base bond (Loading efficiency, LE=77.6 mg/g), and the drug release could be controlled with temperature and pH. This property may promote the chitosan graft copolymer to be used in the field of "smart" drug delivery. PMID- 22322113 TI - Intact neurobehavioral development and dramatic impairments of procedural-like memory following neonatal ventral hippocampal lesion in rats. AB - Neonatal ventral hippocampal lesions (NVHL) in rats are considered a potent developmental model of schizophrenia. After NVHL, rats appear normal during their preadolescent time, whereas in early adulthood, they develop behavioral deficits paralleling symptomatic aspects of schizophrenia, including hyperactivity, hypersensitivity to amphetamine (AMPH), prepulse and latent inhibition deficits, reduced social interactions, and spatial working and reference memory alterations. Surprisingly, the question of the consequences of NVHL on postnatal neurobehavioral development has not been addressed. This is of particular importance, as a defective neurobehavioral development could contribute to impairments seen in adult rats. Therefore, at several time points of the early postsurgical life of NVHL rats, we assessed behaviors accounting for neurobehavioral development, including negative geotaxis and grip strength (PD11), locomotor coordination (PD21), and open-field (PD25). At adulthood, the rats were tested for anxiety levels, locomotor activity, as well as spatial reference memory performance. Using a novel task, we also investigated the consequences of the lesions on procedural-like memory, which had never been tested following NVHL. Our results point to preserved neurobehavioral development. They also confirm the already documented locomotor hyperactivity, spatial reference memory impairment, and hyperresponsiveness to AMPH. Finally, our rseults show for the first time that NVHL disabled the development of behavioral routines, suggesting dramatic procedural memory deficits. The presence of procedural memory deficits in adult rats subjected to NHVL suggests that the lesions lead to a wider range of cognitive deficits than previously shown. Interestingly, procedural or implicit memory impairments have also been reported in schizophrenic patients. PMID- 22322114 TI - Mechanisms of intrinsic force in small human airways. AB - We quantified the magnitude and investigated mechanisms regulating intrinsic force (IF) in human airway smooth muscle (hASM). IF was identified by reducing extracellular calcium (Ca2+) concentration to nominally zero in freshly isolated isometrically mounted 2mm human bronchi. Our results show: (1) the magnitude of IF is ~50% of the maximal total force elicited by acetylcholine (10(-5) M) and is epithelial independent, (2) IF can also be revealed by beta-adrenergic activation (isoproterenol), non-specific cationic channel blockade (La3+) or L-type voltage gated Ca2+ channel blockade (nifedipine), (3) atropine, indomethacin, AA-861, or pyrilamine did not affect IF, (4) IF was reduced by the intracellular Ca2+ ([Ca2+]i) chelating agent BAPTA-AM, (5) omega-conotoxin had no effect on IF. In studies in cultured hASM cells nominally zero Ca2+ buffer and BAPTA-AM reduced [Ca2+]i but isoproterenol and nifedipine did not. Taken together these results indicate that rapid reduction of [Ca2+]i reveals a permissive relationship between extracellular Ca2+, [Ca2+]i and IF. However IF can be dissipated by mechanisms effecting Ca2+ sensitivity. We speculate that an increase of IF, a fundamental property of ASM, could be related to human airway clinical hyperresponsiveness and must be accounted for in in vitro studies of hASM. PMID- 22322115 TI - In vivo and in vitro lung mechanics by forced oscillations: effect of bleomycin challenge. AB - Bleomycin injury causes biomechanical changes secondary to inflammation, tissue remodeling and surfactant changes. We compared lung mechanics in open chest (OC) and tissue strip (TS) to better understand the pathophysiology of the alveolar interface between lung tissue and conducting airways. Thirty nine rats were studied at days 3, 7, and 15 after receiving saline or bleomycin (2.5 Ukg(-1)) intratracheally. Normalized elastance (E), hysteresivity (eta) and exponent (beta) of the power frequency dependence of elastance were determined in OC (lung parenchyma) and TS. Remodeling (hydroxyproline) and inflammation (myeloperoxidase and lung water) parameters were determined. E, eta and beta were higher in OC both in saline and bleomycin groups. The difference (OC-TS) of eta and beta correlated with myeloperoxidase and lung water but not with hydroxyproline. We concluded that differences between lung parenchyma and tissue mechanics are due to mechanical effects of inhomogeneities in saline animals. Changes at the alveolar interface after bleomycin are related to oxidative stress and extravascular lung water. PMID- 22322116 TI - Transcervical carotid stenting with flow reversal is a safe technique for high risk patients older than 70 years. AB - BACKGROUND: Recent evidence regarding carotid revascularization advises against carotid angioplasty and stenting (CAS) in patients aged >70 years with conventional risk for carotid endarterectomy (CEA). The poor outcome of transfemoral CAS in this age group may be explained by the anatomic characteristics of the aortic trunk and supra-aortic vessels in elderly patients, as well as by a high prevalence of aortic arch atheromatosis. Transcervical CAS with flow reversal for cerebral protection avoids these unfavorable characteristics. This study analyzed the short-term and middle-term results of transcervical CAS with flow reversal in patients aged >70 years at high risk for CEA. METHODS: Between January 2006 and January 2011, 219 cases of >70% carotid artery stenosis in high-risk patients aged >70 years (55.7% asymptomatic and 44.3% symptomatic) were treated by transcervical CAS. All patients underwent complete neurologic examination by a stroke neurologist before and after the procedure. Primary end points were stroke, death, or myocardial infarction (MI), technical success, and complications at 30 days. During follow-up, we analyzed the rate of restenosis >=50% and ipsilateral stroke. Data were collected prospectively and outcome was analyzed in all cases, including technical failures. RESULTS: The 30-day combined stroke/death/MI rate was 2.2% (stroke, 1.8%; stroke/death, 2.2%; and MI, 0.45%). In symptomatic patients, stroke/death/MI was 5.1% (stroke, 4.1%; stroke/death, 5.1%). None of the asymptomatic patients suffered stroke, MI, or death postoperatively. Technical success was 96.3% (four inability to cross lesion, two major common carotid dissections, one failed preangioplasty, one stent thrombosis). One cervical hematoma required surgical drainage. At follow-up (18.8 +/- 16.9 months), cumulative (standard error) incidence of >70% restenosis was 3% (1%) at 1 year and 8% (3%) at 2 and 3 years. Only one patient experienced ipsilateral stroke during follow-up. Overall survival (standard error) was 94% (2%) at 1 year and 90% (3%) at 2 and 3 years. CONCLUSIONS: In our experience, transcervical CAS with flow reversal is a safe technique for treating carotid stenosis in patients aged >70 years. We believe that avoiding the aortic arch and tortuous supra-aortic vessels is responsible for the favorable results in this study. PMID- 22322117 TI - Costochondral calcification, osteophytic degeneration, and occult first rib fractures in patients with venous thoracic outlet syndrome. AB - OBJECTIVE: Subclavian vein (SCV) compression in venous thoracic outlet syndrome (TOS) has been attributed to various anatomic factors, but a potential role for costochondral degeneration in the underlying first rib has not been previously examined. The purpose of this study was to examine the frequency of costochondral calcification (CC), osteophytic degeneration (OD), and occult first rib fractures (FRFx) in patients with venous TOS. METHODS: Thirty-seven patients (21 male, 16 female) were referred for surgical treatment of venous TOS during a 12-month period, with a mean age of 30.7 +/- 1.8 year (range, 12-55). Thirteen (35%) had acute SCV effort thrombosis and 24 (65%) had chronic symptoms (>14 days). Twenty (54%) had undergone SCV thrombolysis, 11 (30%) had persistent SCV occlusion, and 10 (27%) had concomitant symptoms of neurogenic TOS. All patients underwent paraclavicular thoracic outlet decompression with complete resection of the first rib to the sternum, with 20 (54%) having concomitant SCV reconstruction. The presence or absence of CC, OD, and FRFx was determined by direct visual examination of the rib at operation and following debridement of the excised specimen. RESULTS: One patient had a cervical rib but there were none with radiographic first rib abnormalities. In contrast, FRFx were observed at surgical resection in 16 of 37 patients (43%). All FRFx were small, nondisplaced, linear lesions located within an area of CC in the anterior rib, typically in association with OD and perivenous soft tissue thickening. The mean age of patients with FRFx was higher than those with a normal first rib (38.1 +/- 1.5 years vs 25.0 +/- 2.3 years; P < .0001), and FRFx were present in 16 of 21 (76%) patients >= 30 years of age but in no patients younger than 30 (P < .0001). CONCLUSIONS: A high proportion (43%) of patients with venous TOS exhibited CC, OD, and a previously undetected FRFx, including 76% of those over the age of 30. These lesions occur in the cartilaginous anterior rib where they are clinically occult and undetected by standard radiographic imaging. We postulate that age related CC may predispose to OD and stress-induced FRFx, and that inflammation, fibrosis, and anatomic distortion in the surrounding soft tissues may contribute to SCV compression. PMID- 22322118 TI - Aneurysmal degeneration of the donor artery after vascular access. AB - OBJECTIVE: This retrospective study analyzed the characteristics, potential risks, and therapeutic options of true aneurysms of the donor artery in arteriovenous fistulas (AVFs) for dialysis access. METHODS: We retrospectively collected data of patients with aneurysmal degeneration (AD) after AVF creation from surgeons who were members of the French Society for Vascular Access, treated from January 2006 to May 2011. The study excluded patients with pseudoaneurysms. Patient demographics, type of access, aneurysm characteristics, symptoms, treatment, and follow-up were recorded. RESULTS: Seven men and three women (mean age, 38.1 +/- 5.3 years) were identified with AD (mean diameter, 44.5; range, 24 80 mm) Mean duration of access was 83.6 +/- 48.8 months. Diagnosis of AD was at 117.5 +/- 53.8 months after access creation. The initial access was radiocephalic, six; ulnobasilic, one; brachiocephalic, two; and brachiobasilic, one. Three patients had two successive accesses: one brachioaxillary polytetrafluoroethylene (PTFE) graft and two proximalizations of a failed radiocephalic AVF. Symptoms were pain and swelling, four; pain related to total thrombosis without signs of ischemia, two; median nerve compression, two; pain related to contained rupture, one; and subacute ischemia due to embolic occlusion of both radial and interosseous arteries, one. AD location was brachial, seven; axillary, one; radial, one; and ulnar, one. Eight patients underwent surgical aneurysm excision associated with interposition bypass using great saphenous vein, two; basilic vein, one; PTFE, three; Dacron, one; and allograft, one. Two patients needed secondary PTFE bypass because of progression of AD to the inflow artery and dilatation of the venous bypass. With a mean follow-up of 20.3 +/- 17 months, all bypasses but one remained patent. CONCLUSIONS: AD is a rare but significant complication of vascular access. Surgical correction should be discussed in most cases due to potential complications. After resection, the choice of reconstructive conduit is not straightforward. PMID- 22322119 TI - Helical EndoStaples enhance endograft fixation in an experimental model using human cadaveric aortas. AB - OBJECTIVE: This study evaluated the contribution of Aptus EndoStaples (Aptus Endosystems, Sunnyvale, Calif) in the proximal fixation of eight endografts used in the endovascular repair of abdominal aortic aneurysms (EVAR). METHODS: Nine human cadaveric aortas were exposed, left in situ, and transected to serve as fixation zones. The Zenith (Cook, Bloomington, Ind), Anaconda (Vascutek, Inchinnan, Scotland, UK), Endurant (Medtronic, Minneapolis, Minn), Excluder (W. L. Gore and Associates, Flagstaff, Ariz), Aptus (Aptus Endosystems), Aorfix (Lombard Medical, Didcot, UK), Talent (Medtronic), and AneuRx (Medtronic) stent grafts were proximally deployed and caudal displacement force (DF) was applied via a force gauge, recording the DF required to dislocate each device >=20 mm from the infrarenal neck. Measurements were repeated after four and six EndoStaples were applied at the proximal fixation zone, as well as after a Dacron graft was sutured at the proximal neck in standard fashion. Finally, a silicone tube was used as a control fixation zone to test the DF of grafts with EndoStaples in a material that exceeded the integrity of a typical human cadaveric aorta and provided a consistent substrate to examine the differential effect of variable degrees of EndoStaple implantation using zero, two, four, and six EndoStaples. RESULTS: In the cadaveric model, the mean DF required to dislocate the endografts without the application of EndoStaples was 19.73 +/- 12.52 N; this increased to 49.72 +/- 12.53 N (P < .0001) when four EndoStaples where applied and to 79.77 +/- 28.04 N when six EndoStaples were applied (P = .003). The DF necessary to separate the conventionally hand-sutured Dacron graft from the aorta was 56 N. In the silicone tube model, the Aptus endograft without EndoStaples withstood 3.2 N of DF. The DF increased to 39 +/- 3 N when two EndoStaples were added, to 71 +/- 6 N when four were added, and to 98 +/- 5 N when six were added. In eight of the 13 cadaver experiments conducted with four and six EndoStaples, the displacement occurred as a result of complete aortic transection proximal to the fixation site, indicating that aortic tissue integrity was the limiting factor in these experiments. CONCLUSIONS: The fixation of eight different endografts was increased by a mean of 30 N with four Aptus EndoStaples and by a mean of 57 N with six EndoStaples in this model. Endostaples can increase endograft fixation to levels equivalent or superior to that of a hand-sewn anastomosis. The application of six EndoStaples results in aortic tissue failure above the fixation zone, demonstrating fixation strength that exceeds inherent aortic integrity in these cadavers. PMID- 22322120 TI - Blunt abdominal aortic injury. AB - BACKGROUND: Blunt abdominal aortic injury (BAAI) is a rare injury with less than 200 cases in the current reported world literature, mostly in case report format. We sought to describe the experience of a high-volume trauma center and to provide a contemporary review of the literature to better understand the natural history and management of this injury. METHODS: This was a retrospective review of patients with BAAI between 1996 and 2010. Data collected included demographics, mechanism of injury, associated injuries, type of intervention, subsequent imaging, and follow-up. BAAI was classified by the presence of external aortic contour abnormality noted as an intimal tear, large intimal flap, pseudoaneurysm, or free rupture. Abdominal aorta zones of injury were classified by possible surgical approaches as zone I (diaphragmatic hiatus to superior mesenteric artery [SMA]), zone II (includes SMA and renal arteries), and zone III (from the inferior aspect of the renal arteries to the aortic bifurcation). RESULTS: We identified 28 individuals (68% male) with BAAI (median age, 28.5; range, 6-61 years). The median injury severity score was 45 (range, 16-75), and 39% were hypotensive at presentation. BAAI presented as intimal tear (21%), large intimal flap (39%), pseudoaneurysm (11%), and free rupture (29%). Zone III was the most common location of injury. Management depended on the location and type of injury: nonoperative (32%), open aortic repair (36%), endovascular repair (21%), and multimodality (10%). Overall mortality was 32%. Most deaths occurred during the initial operative exploration. The mortality rate of free aortic rupture was 100%. Intimal tears resolved or remained stable. Median follow-up was 15.5 months (range, 8 days-7.5 years). Vascular complications due to repair included a thrombosed access femoral artery during an endovascular repair and death of a patient who underwent a hybrid repair. CONCLUSIONS: This is the largest BAAI series described in the English literature at one institution. BAAIs range from intimal tears to free rupture, with outcomes and management correlating with type and location of injury. Nonoperative management with blood pressure control using beta-blockers coupled with antiplatelet therapy and close follow-up is successful in individuals with intimal tears with minimal thrombus formation because they remain stable or resolve on follow-up. Free rupture remains a devastating injury, with 100% mortality. For all other categories of aortic injury, successful repair correlates with a favorable prognosis. PMID- 22322121 TI - Mesenteric artery complications during angioplasty and stent placement for atherosclerotic chronic mesenteric ischemia. AB - OBJECTIVE: The purpose of this study was to describe the incidence, management, and outcomes of mesenteric artery complications (MACs) during angioplasty and stent placement (MAS) for chronic mesenteric ischemia (CMI). METHODS: We retrospectively reviewed the clinical data of 156 patients treated with 173 MAS for CMI (1998-2010). MACs were defined as procedure-related mesenteric artery dissection, stent dislodgement, embolization, thrombosis, or perforation. End points were procedure-related morbidity and death. RESULTS: There were 113 women and 43 men (mean age, 73 +/- 14 years). Eleven patients (7%) developed 14 MACs, including distal mesenteric embolization in six, branch perforation in three, dissection in two, stent dislodgement in two, and stent thrombosis in one. Five patients required adjunctive endovascular procedures, including in two patients each, catheter-directed thrombolysis or aspiration, retrieval of dislodged stents, and placement of additional stents for dissection. Five patients (45%) required conversion to open repair: two required evacuation of mesenteric hematoma, two required mesenteric revascularization, and one required bowel resection. There were four early deaths (2.5%) due to mesenteric embolization or myocardial infarction in two patients each. Patients with MACs had higher rates of mortality (18% vs 1.5%) and morbidity (64% vs 19%; P <.05) and a longer hospital length of stay (6.3 +/- 4.2 vs 1.6 +/- 1.2 days) than those without MACs. Periprocedural use of antiplatelet therapy was associated with lower risk of distal embolization or vessel thrombosis (odds ratio, 0.2; 95% confidence interval, 0.06-0.90). Patients treated by a large-profile system had a trend toward more MACs (odds ratio, 1.8; 95% confidence interval, 0.7-26.5; P = .07). CONCLUSIONS: MACs occurred in 7% of patients who underwent MAS for CMI and resulted in higher mortality, morbidity, and longer hospital length of stay. Use of antiplatelet therapy reduced the risk of distal embolization or vessel thrombosis. There was a trend toward more MACs in patients who underwent interventions performed with a large-profile system. PMID- 22322122 TI - Outcomes of percutaneous endovascular intervention for type II endoleak with aneurysm expansion. AB - OBJECTIVE: Type II endoleak (T2EL) with aneurysm expansion is believed to place patients at risk for aneurysm-related mortality (ARM). Treatment with glue and/or coil embolization of the aneurysm sac, inferior mesenteric artery (IMA), and lumbar branches via translumbar or transarterial approaches has been utilized to ablate such endoleaks, and thus decrease ARM. We evaluated the midterm results of percutaneous endovascular treatment of T2EL with aneurysm expansion. METHODS: Single-institution, 5-year (January 2003 to August 2008) retrospective study of all endovascular interventions for T2EL with sac expansion. Blinded, independent review of all available pre- and post-T2EL intervention computed tomography (CT) scans was performed. Aneurysm sac maximal transverse diameters and aneurysm sac growth rates prior to and following T2EL intervention were analyzed. RESULTS: Forty-two patients (34 male, eight female; mean age, 75) underwent T2EL intervention at 26 +/- 20 months after endovascular aneurysm repair (EVAR) and were subsequently followed for 23 +/- 20 months. Seven out of 42 patients (17%) underwent repeat T2EL intervention. Interventions included 44 translumbar sac embolizations, and transcatheter embolizations of nine IMAs and seven lumbar/hypogastric arteries. Aneurysm diameter was 6.1 +/- 1.6 cm at EVAR, 6.6 +/ 1.5 cm at initial T2EL treatment, and 6.9 +/- 1.7 cm at last follow-up. There were no significant differences in the rates of aneurysm sac growth pre- and post T2EL treatment. At last follow-up imaging, recurrent or persistent T2EL was noted in 72% of patients. Of 42 patients, nine (21%) received operative endoluminal correction of occult type I or type III endoleaks that were diagnosed during the T2EL angiographic intervention. There were no aneurysm ruptures or ARMs during follow-up; overall mortality for the 5-year study period was 24%. CONCLUSIONS: In this series, percutaneous endovascular intervention for type II endoleak with aneurysm sac growth does not appear to alter the rate of aneurysm sac growth, and the majority of patients display persistent/recurrent endoleak. However, diagnostic angiographic evaluation may reveal unexpected type I and III endoleaks and is therefore recommended for all patients with T2EL and sac growth. While coil and glue embolization of aneurysm sac and selected branch vessels does not appear to yield benefit in our series, the diagnosis and subsequent definitive treatment of previously occult type I and III endoleaks may explain the absence of delayed rupture and ARM in our series. PMID- 22322123 TI - Women derive less benefit from elective endovascular aneurysm repair than men. AB - BACKGROUND: Women have a lower chance of surviving elective open abdominal aortic repair. The reasons for this are not clear. Endovascular repair has clearly reduced early and midterm morbidity and mortality for patients with large abdominal aortic aneurysms (AAAs). However, most patients are male. It is unclear whether there has been any reduction in elective morbidity for females or what the extent of that reduction has been. We prospectively analyzed outcomes for elective endovascular aneurysm repair (EVAR) in women at our center and compared results with those for elective open surgery and emergent open and endovascular repair. METHODS: All patients undergoing elective and emergency AAA from 2002 to 2009 were prospectively entered into a database. Demographic details, including gender, were tabulated. Outcome measures were operative blood loss, incidence of type 1 endoleaks, length of in-hospital stay, postoperative complications, 30-day all-cause mortality, and secondary interventions during the follow-up period. Statistical analysis was performed using Fischer exact test and Student t test. A multivariate analysis was also performed. RESULTS: From 2002 to 2009, there were 2631 abdominal aortic aneurysms (AAA) open and endovascular repairs performed in our center (1698 endovascular aneurysm repairs [EVARs], 933 "open"). Males comprised 1995 (76%) of patients; females 636 (24%). There were 1592 elective EVARs (1248 male, 344 female) and 106 emergency EVARs (73 male, 33 female). Elective open repair was performed in 788 patients (579 male, 209 female) and emergency open repair in 149 (73 male, 76 female). For women, elective EVAR resulted in significantly greater mortality rates than men (3.2% vs 0.96%, P < .005). There was a greater incidence of intraoperative aortic neck or iliac artery rupture (4.1% vs 1.2% P = .002) and use of Palmaz stents for type 1 endoleaks (16.1% vs 8%, P = .0009). Mean blood loss was greater in females (327 mL vs 275 mL, P = .038). Perioperative complications were also more frequent in women: leg ischemia (3.5% vs 0.6%, P = .003) and colon ischemia requiring colectomy (0.9% vs 0.2%, P = .009). Mean hospital stay was also longer (3.7 days vs 2.2 days, P = .0001). In contrast, there were no gender differences for any of these outcome measures for elective open repair or emergency open surgery or EVAR. There was no significant difference in death rates between EVAR and open repair in women (3.2% vs 5.7%). In males, the 30-day mortality was 0.96% for elective EVAR and 4.7% for elective open surgery. Following logistic regression, female gender remains a significant risk even when the effects of aneurysm size and age are considered (odds ratio 3.4, P < .01). CONCLUSIONS: Mortality for females undergoing elective EVAR is significantly greater than for males. It is also more hazardous. Colon ischemia, native arterial rupture, and type 1 endoleaks are more frequent. Elective endovascular aneurysm repair benefits men more than women. PMID- 22322124 TI - The effect of cord cleansing with chlorhexidine on neonatal mortality in rural Bangladesh: a community-based, cluster-randomised trial. AB - BACKGROUND: Up to half of neonatal deaths in high mortality settings are due to infections, many of which can originate through the freshly cut umbilical cord stump. We aimed to assess the effectiveness of two cord-cleansing regimens with the promotion of dry cord care in the prevention of neonatal mortality. DESIGN: We did a community-based, parallel cluster-randomised trial in Sylhet, Bangladesh. We divided the study area into 133 clusters, which were randomly assigned to one of the two chlorhexidine cleansing regimens (single cleansing as soon as possible after birth; daily cleansing for 7 days after birth) or promotion of dry cord care. Randomisation was done by use of a computer-generated sequence, stratified by cluster-specific participation in a previous trial. All livebirths were eligible; those visited within 7 days by a local female village health worker trained to deliver the cord care intervention were enrolled. We did not mask study workers and participants to the study interventions. Our primary outcome was neonatal mortality (within 28 days of birth) per 1000 livebirths, which we analysed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT00434408. RESULTS: Between June, 2007, and September, 2009, we enrolled 29 760 newborn babies (10 329, 9423, and 10 008 in the multiple-cleansing, single-cleansing, and dry cord care groups, respectively). Neonatal mortality was lower in the single-cleansing group (22.5 per 1000 livebirths) than it was in the dry cord care group (28.3 per 1000 livebirths; relative risk [RR] 0.80 [95% CI] 0.65-0.98). Neonatal mortality in the multiple-cleansing group (26.6 per 1000 livebirths) was not statistically significantly lower than it was in the dry cord care group (RR 0.94 [0.78-1.14]). Compared with the dry cord care group, we recorded a statistically significant reduction in the occurrence of severe cord infection (redness with pus) in the multiple-cleansing group (risk per 1000 livebirths=4.2 vs risk per 1000 livebirths=1.2; RR 0.35 [0.15-0.81]) but not in the single-cleansing group (risk per 1000 livebirths=3.3; RR 0.77 [0.40-1.48]). INTERPRETATION: Chlorhexidine cleansing of a neonate's umbilical cord can save lives, but further studies are needed to establish the best frequency with which to deliver the intervention. FUNDING: United States Agency for International Development and Save the Children's Saving Newborn Lives program, through a grant from the Bill & Melinda Gates Foundation. PMID- 22322125 TI - Chlorhexidine cord cleansing to reduce neonatal mortality. PMID- 22322126 TI - Topical application of chlorhexidine to neonatal umbilical cords for prevention of omphalitis and neonatal mortality in a rural district of Pakistan: a community based, cluster-randomised trial. AB - BACKGROUND: Umbilical cord infection (omphalitis) is a risk factor for neonatal sepsis and mortality in low-resource settings where home deliveries are common. We aimed to assess the effect of umbilical-cord cleansing with 4% chlorhexidine (CHX) solution, with or without handwashing with antiseptic soap, on the incidence of omphalitis and neonatal mortality. METHODS: We did a two-by-two factorial, cluster-randomised trial in Dadu, a rural area of Sindh province, Pakistan. Clusters were defined as the population covered by a functional traditional birth attendant (TBA), and were randomly allocated to one of four groups (groups A to D) with a computer-generated random number sequence. Implementation and data collection teams were masked to allocation. Liveborn infants delivered by participating TBAs who received birth kits were eligible for enrolment in the study. One intervention comprised birth kits containing 4% CHX solution for application to the cord at birth by TBAs and once daily by family members for up to 14 days along with soap and educational messages promoting handwashing. One intervention was CHX solution only and another was handwashing only. Standard dry cord care was promoted in the control group. The primary outcomes were incidence of neonatal omphalitis and neonatal mortality. The trial is registered with ClinicalTrials.gov, number NCT00682006. FINDINGS: 187 clusters were randomly allocated to one of the four study groups. Of 9741 newborn babies delivered by participating TBAs, factorial analysis indicated a reduction in risk of omphalitis with CHX application (risk ratio [RR]=0.58, 95% CI 0.41-0.82; p=0.002) but no evidence of an effect of handwashing (RR=0.83, 0.61-1.13; p=0.24). We recorded strong evidence of a reduction in neonatal mortality in neonates who received CHX cleansing (RR=0.62, 95 % CI 0.45-0.85; p=0.003) but no evidence of an effect of handwashing promotion on neonatal mortality (RR=1.08, 0.79-1.48; p=0.62). We recorded no serious adverse events. INTERPRETATION: Application of 4% CHX to the umbilical cord was effective in reducing the risk of omphalitis and neonatal mortality in rural Pakistan. Provision of CHX in birth kits might be a useful strategy for the prevention of neonatal mortality in high mortality settings. FUNDING: The United States Agency for International Development. PMID- 22322127 TI - Managing wastewater effluent to enhance aquatic receiving ecosystem productivity: a coastal lagoon in Western Australia. AB - Large amounts of waste are generated in urban centers that if properly managed could promote ecological services. In order to promote nutrient cycling and productivity without endangering aquatic ecosystems, management of wastewater treatment and effluent discharges to receiving waters must be assessed on a case by-case basis. We applied this premise to examine a municipal wastewater treated effluent discharge in a shallow oligotrophic coastal lagoon in Western Australia. Three-dimensional hydrodynamic-ecological modeling (ELCOM-CAEDYM) was used to assess the reaction of ecosystem for effluent quality. Two scenarios were evaluated for the summer 2000-2001 period, the actual or "current" (conventional secondary treatment) and an "alternative" (involving substitution of biological nutrient removal by advanced treatment). The residence time of the simulated numerical domain averaged 8.4 +/- 1.3 days. For the current scenario the model successfully estimated phytoplankton biomass, as chlorophyll-a concentration (Chl a), that is within field-measured ranges and previously recorded levels. The model was able to reproduce nitrogen as the main limiting nutrient for primary production in the coastal ecosystem. Simulated surface Chl-a means were 0.26 (range 0.19-0.38) MUg Chl-a/L for the current scenario and 0.37 (range 0.19-0.67) MUg Chl-a/L for the alternative one. Comparison of the alternative scenario with field-measured Chl-a levels suggests moderate primary production increase (16 42%), within local historical variability. These results, suggest that such a scenario could be used, as part of a comprehensive wastewater management optimization strategy, to foster receiving ecosystem's productivity and related ecological services maintaining its oligotrophic state. PMID- 22322128 TI - A new spatial multi-criteria decision support tool for site selection for implementation of managed aquifer recharge. AB - This study reports the development of a new spatial multi-criteria decision analysis (SMCDA) software tool for selecting suitable sites for Managed Aquifer Recharge (MAR) systems. The new SMCDA software tool functions based on the combination of existing multi-criteria evaluation methods with modern decision analysis techniques. More specifically, non-compensatory screening, criteria standardization and weighting, and Analytical Hierarchy Process (AHP) have been combined with Weighted Linear Combination (WLC) and Ordered Weighted Averaging (OWA). This SMCDA tool may be implemented with a wide range of decision maker's preferences. The tool's user-friendly interface helps guide the decision maker through the sequential steps for site selection, those steps namely being constraint mapping, criteria hierarchy, criteria standardization and weighting, and criteria overlay. The tool offers some predetermined default criteria and standard methods to increase the trade-off between ease-of-use and efficiency. Integrated into ArcGIS, the tool has the advantage of using GIS tools for spatial analysis, and herein data may be processed and displayed. The tool is non-site specific, adaptive, and comprehensive, and may be applied to any type of site selection problem. For demonstrating the robustness of the new tool, a case study was planned and executed at Algarve Region, Portugal. The efficiency of the SMCDA tool in the decision making process for selecting suitable sites for MAR was also demonstrated. Specific aspects of the tool such as built-in default criteria, explicit decision steps, and flexibility in choosing different options were key features, which benefited the study. The new SMCDA tool can be augmented by groundwater flow and transport modeling so as to achieve a more comprehensive approach to the selection process for the best locations of the MAR infiltration basins, as well as the locations of recovery wells and areas of groundwater protection. The new spatial multicriteria analysis tool has already been implemented within the GIS based Gabardine decision support system as an innovative MAR planning tool. PMID- 22322129 TI - Population-specificity of human DNA methylation. AB - BACKGROUND: Ethnic differences in human DNA methylation have been shown for a number of CpG sites, but the genome-wide patterns and extent of these differences are largely unknown. In addition, whether the genetic control of polymorphic DNA methylation is population-specific has not been investigated. RESULTS: Here we measure DNA methylation near the transcription start sites of over 14, 000 genes in 180 cell lines derived from one African and one European population. We find population-specific patterns of DNA methylation at over a third of all genes. Furthermore, although the methylation at over a thousand CpG sites is heritable, these heritabilities also differ between populations, suggesting extensive divergence in the genetic control of DNA methylation. In support of this, genetic mapping of DNA methylation reveals that most of the population specificity can be explained by divergence in allele frequencies between populations, and that there is little overlap in genetic associations between populations. These population specific genetic associations are supported by the patterns of DNA methylation in several hundred brain samples, suggesting that they hold in vivo and across tissues. CONCLUSIONS: These results suggest that DNA methylation is highly divergent between populations, and that this divergence may be due in large part to a combination of differences in allele frequencies and complex epistasis or gene * environment interactions. PMID- 22322130 TI - Different wall motion patterns of three consecutive episodes of takotsubo cardiomyopathy in the same patient. PMID- 22322131 TI - Quantitative assessment of right ventricular function and severity of pure mitral stenosis with 64-section multi-detector row CT: comparison with magnetic resonance imaging. PMID- 22322132 TI - A nanoforest structure for practical surface-enhanced Raman scattering substrates. AB - A nanoforest structure for surface-enhanced Raman scattering (SERS) active substrates is fabricated and analyzed. The detailed morphology of the resulting structure can be easily controlled by modifying the process parameters such as initial gold layer thickness and etching time. The applicability of the nanoforest substrate as a label-free SERS immunosensor is demonstrated using influenza A virus subtype H1N1. Selective binding of the H1N1 surface antigen and the anti-H1 antibody is directly detected by the SERS signal differences. Simple fabrication and high throughput with strong in-plane hot-spots imply that the nanoforest structure can be a practical sensing component of a chip-based SERS sensing system. PMID- 22322133 TI - Identification of a novel F11 missense mutation (Ile463Ser) in a family with congenital factor XI deficiency. AB - We investigated an asymptomatic 19-year-old patient with factor XI deficiency diagnosed in the context of presurgical laboratory screening. The F11 gene was analyzed and a novel missense mutation I463S in exon 12 was identified in heterozygosity in the proband. His mother, also diagnosed with asymptomatic factor XI deficiency, was found to be heterozygous for the same mutation. This novel amino acid substitution in the serine protease catalytic domain appears to be responsible for the low factor XI levels in both individuals. PMID- 22322134 TI - Severe pregnancy complications are associated with elevated factor VIII plasma activity. AB - The objective of this study is to investigate the prevalence of elevated factor VIII activity among women with severe complications of pregnancy. The study group included 49 patients with a previous history of pregnancy complications: severe preeclampsia (n = 9); intrauterine fetal death (IUFD) (n = 9); severe intrauterine fetal growth restriction (IUGR) (n = 12); IUGR and preeclampsia (n = 7); preeclampsia and placental abruption (n = 2); IUFD and IUGR (n = 5); and abruptio placenta (n = 5). The control group included 49 healthy women who had had at least one normal pregnancy. Seventeen women of the study group (34.6%) had elevated factor VIII activity compared to one woman (2.1%) in the control group (P < 0.05). The mean level of factor VIII was 159 +/- 52% and 88 +/- 17.4% of normal activity (mean +/- SD, t-test, P < 0.05). Importantly, 10 women of the study group (20.4%) had only elevated factor VIII activity with no other known thrombophilia compared to one woman (2.1%) in the control group (P < 0.05). Elevated plasma activity of factor VIII might be a risk factor for severe pregnancy complications. PMID- 22322135 TI - Subclinical central nervous system involvement and thrombophilic status in young thalassemia intermedia patients of Greek origin. AB - Beta thalassemia is known to be characterized by a hypercoagulable state, with prothrombotic factors present and thrombotic event development in a number of patients. The aim of the present study was to evaluate subclinical involvement of the central nervous system (CNS) in young patients with thalassemia intermedia, the use of nonimaging, noninvasive laboratory methods for detecting relevant abnormalities, and the frequency and possible correlation of coagulation abnormalities with CNS lesions. In this cross-sectional study, 24 young patients with thalassemia intermedia were evaluated (mean age 12 +/- 4.6 years, range 4.5 20 years). Patients underwent neurological examination, inherited and acquired coagulation defect testing, as well as neurophysiologic and neuroimaging evaluation. Patients aged 6-16 also had intelligence scores measured. With regards to coagulation, a decrease in antithrombin III (ATIII), protein C and protein S activity was found in 4.1, 54.16 and 45.8% of patients, respectively. Increased D-dimers, as well as thrombin-antithrombin complex (TAT) and prothrombin fragment (F1 + 2) values were found in 12.5, 62.5 and 8.33% of patients, respectively. Heterozygosity and homozygosity for the methylenetetrahydrofolate reductase mutation was found in 45.8 and 12.5% of patients, whereas heterozygosity for factor V Leiden and G20210FII was found in 8.33 and 12.5% of patients, respectively, with increased prevalence compared to Greek population. Neuroimaging evaluation was normal in all patients. Neurophysiologic evaluation revealed abnormal findings in 33.3% of patients on electroencephalogram (EEG), 16% on brain auditory-evoked potentials (BAEPs) and 4.12% on somatosensory evoked potentials (SEPs). Visual-evoked potentials (VEPs) were normal in all patients. A statistically significant difference was found between low protein C values, as well as high platelet counts, with abnormal EEG findings (P = 0.004 and P = 0.039, respectively). Transcranial Doppler (TCD) measurements revealed increased peak systolic velocities in anterior and posterior cerebral arteries and in basilar artery in 57, 38 and 41% of patients, respectively, as compared to healthy population values. On the contrary, decreased mean velocities were found both on middle cerebral artery and pars terminalis of internal carotid examination in 28.5% of patients. Patients with pathological findings on TCD study had lower hematocrit (P = 0.049) and younger age (P = 0.001) than patients with normal measurements. With regards to intelligence scores, mean intelligence quotient (IQ) was 100 +/- 19.1, with 11.7% of patients demonstrating IQ below 85. The study results confirm the early presence of hemostatic changes in patients with thalassemia intermedia. Additionally, they demonstrate subclinical CNS involvement starting at childhood. For such involvement detection, in addition to neuroimaging, neurophysiological and neuropsychological evaluation is warranted. PMID- 22322136 TI - Relationship between short activated partial thromboplastin times, thrombin generation, procoagulant factors and procoagulant phospholipid activity. AB - Short activated partial thromboplastin times (APTTs) are associated with thrombosis. However, what short APTTs actually represent in terms of possible mechanistic pathways is not well characterized. We have assessed thrombin generation as compared with levels of procoagulant factor (fibrinogen, V, VIII, IX, XI and XII) activities, von Willebrand factor level and activity using collagen binding, as well as procoagulant phospholipid activity, in 113 consecutive samples exhibiting a short APTT compared with an equal number of age matched and sex-matched samples yielding a normal APTT. We found a significant difference in peak thrombin generation, velocity index and area under the curve between the two groups, and that thrombin generation markers correlated with the APTT, procoagulant phospholipid activity and several procoagulant clotting factors. We conclude that short APTTs represent a procoagulant milieu, as represented by heightened thrombin generation and several other heightened procoagulant activities, which may help explain the association with thrombosis. PMID- 22322137 TI - Cost effectiveness of prophylactic treatment with activated prothrombin complex concentrate in a patient with inhibitor-positive hemophilia A. AB - Patients with hemophilia and high titers of inhibitors are hard to treat during bleeding events and consequently are more likely to incur high treatment costs and to experience deterioration in quality of life. We report here the case of a boy with hemophilia A and high titers of inhibitors who responded well to prophylactic activated prothrombin complex concentrate (APCC) treatment. Previously, he had to be hospitalized frequently because of painful bleeding of target joints of the knee and ankle. At the age of 4 years and 3 months, APCC prophylaxis at a dose of 60 U/kg, three times a week, was initiated together with on-demand therapy with recombinant factor VIIa. This reduced the frequency and severity of bleeding and ended the need for hospitalization. This, together with a decreased requirement for bypass agents, APCC treatment significantly reduced the cost of treatment for this patient. PMID- 22322138 TI - Reference values for thrombotic markers in children. AB - Thromboembolic events are an increasingly common problem encountered in children. The laboratory diagnosis of thrombotic disorders in children differs from that in adults. To establish the normal reference of natural anticoagulant parameters in children of different age groups, plasma from healthy children between the ages of 2 months and 16 years (n = 127) and adults (n = 30) were assayed for a disintegrin-like and metalloprotease with thrombospondin type 1 domain 13 (ADAMTS 13), von Willebrand factor collagen-binding activity (vWF:CB), tissue factor pathway inhibitor (TFPI), homocyteine and natural anticoagulants. Children were divided into four age groups: less than 1 year, 1-5 years, 6-10 years, and 11-16 years. The reference values for ADAMTS 13, homocysteine, and protein C activity were significantly lower in children of all age groups compared with those in the adults. Similarly, those for protein C antigen, total protein S, free protein S and antithrombin III (AT III) for children less than 1 year were significantly lower than in the adults. On the contrary, TFPI levels were significantly higher in the children for all age groups when compared with the adults. vWF:CB levels were comparable across all groups. There are age-related physiologic differences in ADAMTS-13, TFPI, homocysteine and natural anticoagulants between children and adults. Our data will provide physicians with a useful reference guide in interpreting test results of inhibitors of hemostatic parameters in children suspected of thrombotic disorders. PMID- 22322139 TI - Cerebral thrombosis in patients with beta-thalassemia: a systematic review. AB - A hypercoagulable state has been documented in patients with beta-thalassemia. It could result in thromboembolic events in several organs including brain involvement, which deserves particular attention. We summarized the prevalence of cerebral involvement in patients with beta-thalassemia worldwide. We conducted an electronic search on PUBMED (MEDLINE), SCOPUS, and Google Scholar databases up to January 2011. Overall 152 thalassemic patients with cerebral thromboembolic events and a proportion of 1.13% (134 of 11770) were recorded. From all patients with cerebral thromboembolic events, 74 (48%) were splenectomized. Cerebral thromboembolic events were reported after transfusion in six beta-thalassemia major, and two beta-thalassemia intermedia patients. Three beta-thalassemia major patients had irregular transfusion and 22 beta-thalassemia intermedia patients were not transfused. Thrombocytosis were determined in 11 beta-thalassemia major, and 15 beta-thalassemia intermedia patients. Cardiomyopathy was present in 13 beta-thalassemia major and four beta-thalassemia intermedia patients. Also, nine beta-thalassemia major patients had diabetes. Activated protein C resistant, decreased protein C or protein S or plasminogen level was detected in eight beta thalassemia major patients. Cerebral involvement appears to be associated with increasing age, transfusion naivety, splenectomy, thrombocytosis, intensive transfusion, decreased protein C level, and having risk factors for cerebrovascular accident such as cardiomyopathy, and diabetes. In light of these findings, diagnostic MRI is recommended in high-risk groups to screen for early asymptomatic brain damage. If brain ischemia is found, the administration of antiplatelet aggregants or blood transfusion is likely to be beneficial. In addition, in thalassemic patients who complicated with a thromboembolic event, secondary prophylaxis could be helpful to prevent cerebral thromboembolic events. PMID- 22322140 TI - Use of objective efficacy criteria for evaluation of von Willebrand factor/factor VIII concentrates. AB - von Willebrand disease (VWD) is the most common inherited coagulation disorder and is typically treated by restoring the deficient von Willebrand factor (VWF) with exogenous VWF or by stimulating release of endogenous VWF with desmopressin. Assessment of treatment efficacy is complex because there are no standardized criteria or consistent methodology in their application. The traditionally used four-point Likert scale, with criteria that are not clearly defined or easily quantifiable, relies on a subjective rating of efficacy, and is thus open to observer bias. This article presents a novel approach to assessing efficacy of VWF replacement therapy. A new objective scoring system for assessment of the treatment efficacy of bleeding episodes (objective set of criteria for evaluation of treatment efficacy in VWD) was developed to assess a new-generation human plasma-derived VWF/coagulation factor VIII concentrate (Wilate). This manuscript analyzes the results obtained using a traditional subjective scoring system for hemostatic efficacy and compares them with results obtained when a specifically developed set of stringent objective and well defined success/failure criteria are applied in a clinical trial setting. This new assessment tool provided improved objectification of the subjective judgments obtained from the recipients of the replacement therapy. A validated tool like this could ultimately be applied to clinical comparability studies for the multiplicity of new generation replacement products, as healthcare providers, regulatory agencies, and manufacturers must now consider the additional benefits conveyed by treatment modalities, such as treatment duration, alternative dosing regimens, and treatment frequency. The objective criteria appear to be more robust and present a more conservative assessment of treatment efficacy while avoiding observer and recipient bias and inconsistencies. This new approach may be a more suitable alternative for hemostatic assessment of coagulation products in VWD patients than the currently used subjective methods. PMID- 22322141 TI - A prospective randomised clinical pilot study to compare the effectiveness of Biobrane(r) synthetic wound dressing, with or without autologous cell suspension, to the local standard treatment regimen in paediatric scald injuries. AB - BACKGROUND: Scald is the most common cause of burn in children in Australia. The time taken by the burn wound to heal impacts on scar outcome. Commonly scald injuries are treated conservatively; in our unit the practice is that if healing does not occur within 10 days, surgery is used to aid healing with the aim of improving scar outcome. This randomised controlled pilot study compares early treatment regimens to facilitate tissue salvage and reduce the incidence of definitive surgery at 10 days following scald injury. METHODS: All paediatric patients with partial thickness scald injury were clinically assessed between July 1, 2009 and June 30, 2010. A burn of 2% TBSAB or more and deemed not to heal within 10 days, were considered for the trial. These patients were randomised to one of three treatment arms: the local standard treatment (IntrasiteTM, ActicoatTM and Duoderm((r)) dressings every 2-3 days) with surgery at 10 days, Biobrane((r)) only or Biobrane((r)) and autologous cell suspension using the ReCell((r)) kit. The primary outcome was surgery performed after 10 days; secondary outcomes were rates of healing, pain experienced, and scar outcomes. RESULTS: 15% of scald presentations in the 12 month period met the eligibility criteria. 13 patients were recruited into the pilot study; early intervention was associated with a decreased time to healing with fewer dressing changes, less pain and better scar outcomes. CONCLUSION: Investment of surgical resources in the acute stages within 4 days of injury saved on nursing time, dressing, analgesic and scar management costs. PMID- 22322142 TI - Paying it forward. PMID- 22322143 TI - Pain and obesity. PMID- 22322144 TI - Anti-Mullerian hormone (AMH) profiles as a novel biomarker to evaluate the existence of a functional cryptorchid testis in Japanese Black calves. AB - Anti-Mullerian hormone (AMH) and testosterone (T) profiles in blood were investigated before and after an hCG stimulation test to assess their sensitivity and specificity for the existence of a functional cryptorchid testis in Japanese Black calves. The hCG (3,000 IU) was administered on Day 0, and peripheral blood was collected on Days 0 (just before hCG injection), 5 and 7 in intact male calves (Intact; n=19), bilateral castrated calves (Castrated; n=17), unilateral cryptorchid calves, which abdominal testis could been extracted (Uni-crypto; n=9). Castration of a descended testis was carried in the Castrated and Uni Crypto groups on Day -14. The AMH detectability and the optimum cut-off point for T levels using the receiver operating characteristic curve were verified to characterize the cryptorchid testis. AMH values on Day 0 were 21.1 +/- 5.1 and 29.0 +/- 7.5 ng/ml in the Intact and Uni-crypto groups, respectively (Mean +/- SEM). AMH levels were under the detection limit in the Castrated group (i.e., < 0.006 ng/ml). T showed its peak levels on Day 5 in the Intact group (26.8 +/- 4.2 ng/ml), while it remained low in the Castrated group (< 0.9 ng/ml) and did not show a significant difference in the Uni-crypto group. The detectable levels for AMH was 0.006 ng/ml, and the optimum cut-off point for T was 0.9 ng/ml; the sensitivity and specificity for evaluation of testicular descent into the scrotum were 1.0 for both the AMH and T levels. The detection rates in the Uni-crypto group using them were 1.0 and 0.57 for AMH on Day 0 and T on Days 5 or 7, respectively. In conclusion, plasma AMH profiles could be used as a novel biomarker to evaluate the existence of a functional cryptorchid testis in Japanese Black calves. PMID- 22322145 TI - Epigenetic status and full-term development of bovine cloned embryos treated with trichostatin A. AB - We examined the comprehensive epigenetic status, including histone H3 and H4 acetylation, DNA methylation and level of mRNA transcripts of bovine somatic cell nuclear transfer (SCNT) embryos treated with trichostatin A (TSA), along with their full-term developmental efficacy. Treatment with 50 nM TSA enhanced early developmental competence; increased acetylation of two histones, H3K9K14 and H4K8, at the blastocyst stage; and maintained the DNA methylation status of the satelliteI sequence in bovine SCNT embryos. The difference in IGFBP-3 transcript levels between in vivo and SCNT embryos disappeared in SCNT embryos after treatment with 50 nM TSA. Pregnancy, full-term developmental competence and body weight at birth of offspring did not differ between SCNT embryos treated with 50 nM TSA and untreated embryos. These results suggest that treatment with TSA improves preimplantation development and changes the epigenetic status but does not promote the full-term development competence in bovine SCNT embryos. PMID- 22322146 TI - Enhanced production of volatile fatty acids (VFAs) from sewage sludge by beta cyclodextrin. AB - Organic matter in sewage sludge can be converted into volatile fatty acids (VFAs) as renewable carbon sources. This work for the first time demonstrates that beta cyclodextrin (beta-CD) molecules enhance sludge hydrolysis for production of VFAs. With 0.2gbeta-CDg(-1) dried solids (DSs), the increment rate for VFAs peaked at 4200gg(-1)DSsg(-1) beta-CD, with acetate and propionate as the predominant VFAs. Compositional and microbial community analyses confirm that the beta-CD molecules break a cell's membrane, such that it releases intracellular substances. Although beta-CD molecules inhibited activities of methanogens, they did not impair those of acid-forming bacteria, thereby demonstrating that beta-CD assisted VFAs are renewable organic carbon sources, except in anaerobic digestion processes. PMID- 22322147 TI - Accumulation characteristics of soluble algal products (SAP) by a freshwater microalga Scenedesmus sp. LX1 during batch cultivation for biofuel production. AB - Algae cultivation is the essential basis for microalgal biofuel production. Soluble algal products (SAP) are significant obstacle to large-scale, high-cell density cultivation processes. SAP accumulation during batch cultivation of Scenedesmus sp. LX1 (a unique strain accumulating lipid substantially while growing fast under low-nutrient conditions) with different initial nitrogen concentrations (7.4-34.0mgNL(-1)) was investigated. The SAP content varied in the range of 3.4-17.4mgDOCL(-1) at stationary phase, with average yield per cell of 0.5-2.5pgDOCcell(-1). High SAP accumulation up to 15.2-17.4mgDOCL(-1) were observed with initial nitrogen above 20.2mgNL(-1). The maximum SAP production rate per unit culture volume (r(SAP)) was 2.6mgDOC(Ld)(-1) and that per cell (nu(SAP)) was 1.5pgDOC(celld)(-1). The r(SAP) increased with cell growth rate and decreased with cell density linearly. The SAP accumulation was majorly due to the release of growth-associated products. PMID- 22322148 TI - Ethanol production from sorghum by a microwave-assisted dilute ammonia pretreatment. AB - The efficiency of a batch microwave-assisted ammonia heating system was investigated as pretreatment for sweet sorghum bagasse and its effect on porosity, chemical composition, particle size, enzymatic hydrolysis and fermentation into ethanol evaluated. Sorghum bagasse, fractionated into three particle size groups (9.5-18, 4-6 and 1-2mm), was pretreated with ammonium hydroxide (28% v/v solution) and water at a ratio of 1:0.5:8 at 100, 115, 130, 145 and 160 degrees C for 1h. Simon's stain method revealed an increase in the porosity of the biomass compared to untreated biomass. The most lignin removal (46%) was observed at 160 degrees C. About 90% of the cellulose and 73% of the hemicellulose remained within the bagasse. The best glucose yields and ethanol yields (from glucose only) among all different pretreatment conditions averaged 42/100g dry biomass and 21/100g dry biomass, respectively with 1-2mm sorghum bagasse pretreated at 130 degrees C for 1h. PMID- 22322149 TI - Interferon modulates central nervous system function. AB - The interferons (IFNs) are an endogenous pleiotropic family of cytokines that perform fundamental physiological functions as well as protecting host organisms from disease and in maintaining homeostasis. This review covers the effects of endogenous IFN on the nervous system. It starts with the description of its receptors, followed how it modulate neuronal activity, mood, sleep, temperature, the endocrine system, the opioid system and how it regulate food consumption and the immune system. Similar to other multifunctional cytokines, an excessive or inappropriate activity of IFNs can cause toxicity and even death. Furthermore, IFNs are currently the major treatment modality for several malignant and non malignant diseases such as chronic hepatitis C and B, multiple sclerosis, hematological malignancies, malignant melanoma, renal cell carcinoma, etc. PMID- 22322150 TI - Neuronal correlates to consciousness. The "Hall of Mirrors" metaphor describing consciousness as an epiphenomenon of multiple dynamic mosaics of cortical functional modules. AB - Humans share the common intuition of a self that has access to an inner 'theater of mind' (Baars, 2003). The problem is how this internal theater is formed. Moving from Cook's view (Cook, 2008), we propose that the 'sentience' present in single excitable cells is integrated into units of neurons and glial cells transiently assembled into "functional modules" (FMs) organized as systems of encased networks (from cell networks to molecular networks). In line with Hebb's proposal of 'cell assemblies', FMs can be linked to form higher-order mosaics by means of reverberating circuits. Brain-level subjective awareness results from the binding phenomenon that coordinates several FM mosaics. Thus, consciousness may be thought as the global result of integrative processes taking place at different levels of miniaturization in plastic mosaics. On the basis of these neurobiological data and speculations and of the evidence of 'mirror neurons' the 'Hall of Mirrors' is proposed as a significant metaphor of consciousness. This article is part of a Special Issue entitled: Brain Integration. PMID- 22322151 TI - Delayed intensive acquisition training alleviates the lesion-induced place learning deficits after fimbria-fornix transection in the rat. AB - This study evaluates the effects of two learning paradigms, intensive vs. baseline, on the posttraumatic acquisition of a water maze based place learning task. Rats were subjected either to a control operation (Sham) or to a fimbria fornix (FF) transection, which renders the hippocampus dysfunctional and disrupts the acquisition of allocentric place learning. All animals were administered 30 post-lesion acquisition sessions, which spanned either 10 or 30days. The acquisition period was followed by a 7day pause after which a retention probe was administered. The lesioned animals were divided into 3 groups: i) Baseline Acquisition Paradigm (BAP) once daily for 30days starting 1week post-surgery; ii) Early Intensive Acquisition Paradigm (EIAP) 3 times daily for 10days starting 1week post-surgery; and iii) Late Intensive Acquisition Paradigm (LIAP) 3 times daily for 10days starting 3weeks post-surgery. Within the control animals, one group followed the schedule of BAP, and one group followed the schedule of Intensive Acquisition Paradigm (IAP). All lesioned animals showed an impaired task acquisition. LIAP was beneficial in FF animals, in that it led to a better acquisition of the place learning task than the two other acquisition paradigms. The FF/EIAP group did not show improved acquisition compared to the FF/BAP group. The control animals were not differentially affected by the two learning schedules. The findings have implications for cognitive rehabilitation after brain injury and support the assumption that intensive treatment can lead to an improved learning, even when the neural structures underlying such a process are compromised. However, the timing of intensive treatment needs to be considered further. PMID- 22322152 TI - E Platinum, a newly synthesized platinum compound, induces autophagy via inhibiting phosphorylation of mTOR in gastric carcinoma BGC-823 cells. AB - A tightly regulated catabolic process named autophagy involves the degradation of intracellular components via lysosomes. Here we investigate the antitumor effect of E Platinum, a newly synthesized derivative of oxaliplatin, in vivo and in vitro. E Platinum exhibits growth inhibition of various tumor cells in a dose dependent manner, but the mechanism underlying it is unclear. Based on theory introducing autophagy, we preliminarily investigate whether autophagy could contribute to the antitumor activity of E Platinum. Our results showed that autophagy induced by 12.5 MUM E Platinum in gastric carcinoma BGC-823 cells was significantly characterized by the FITC-fluorescent microtubule associated protein 1 light chain 3 (MAP-LC3), lysosomal-rich/acidic compartments visualized with Lysotracker red (LTR-red) and an accumulation of numerous large autophagic vesicles within the cytoplasm, but not in the control cells. Meanwhile treatment of cells with 12.5 MUM E Platinum resulted in conversion of water soluble LC3 (LC3-I) to lipidated and autophagosome-associated form (LC3-II) as well as increasing expression of autophagy protein Beclin 1. Activation of predominant lysosomal aspartic protease, LAMP-1 and cathepsin D, was demonstrated. Moreover, RNA interference targeting Beclin 1, inhibition of autophagy by 3-methyladenine (3-MA) and chloroquine significantly suppressed the above process as well as the BGC-823 cells growth inhibition triggered by 12.5 MUM E Platinum. Studies of mechanism revealed that E Platinum suppressed activation of mTOR and p70S6K by decreasing phosphorylation of Akt, ERK1/2, JNK and p38 involved in mitogen activated protein kinase signaling. We supported new evidences for E Platinum as a promising antitumor agent, involving with autophagy induction. PMID- 22322153 TI - Perfluorooctanoic acid induces mast cell-mediated allergic inflammation by the release of histamine and inflammatory mediators. AB - Perfluorooctanoic acid (PFOA) has unique physical and chemical characteristics, water and oil repellency, thermal stability, and surfactant properties. PFOA has been regularly found in the blood of animals and humans worldwide, and has become an increasing concern because of its adverse effects in immune system. However, the role of PFOA in the allergic inflammation is not well-known. To further extend the immunotoxicity of PFOA, we examined the role of PFOA on the mast cell mediated allergic inflammation and studied the possible mechanism of action. PFOA dose- and time-dependently increased histamine release from mast cells and serum histamine by the induction of intracellular calcium. PFOA exacerbated the IgE dependent local allergic reaction in the mouse allergy model. PFOA induced gene expression of pro-inflammatory cytokines such as tumor necrosis factor (TNF) alpha, interleukin (IL)-1beta, IL-6, and IL-8 in mast cells. The inducing effect of PFOA on the pro-inflammatory cytokines was nuclear factor-kappaB, p38 mitogen activated protein kinase, and caspase-1 dependent. Furthermore, the activation of cyclooxygenase-2 by PFOA suggests the induction of allergic inflammatory mediators by the PFOA. Our findings provide evidence that PFOA, the known immunotoxic agent, induces mast cell-derived allergic inflammatory reactions by histamine release and expression of pro-inflammatory cytokines. PMID- 22322154 TI - Recent advances in bioinorganic chemistry of bismuth. AB - Bismuth has been used in medicine for over two centuries for the treatment of various diseases, in particular for gastrointestinal disorders, owing to its antimicrobial activity. Recent structural characterization of bismuth drugs provides an insight into assembly and pharmacokinetic pathway of the drugs. Mining potential protein targets inside the pathogen via metallomic/metalloproteomic approach and further characterization on the interactions of bismuth drugs with these targets laid foundation in understanding the mechanism of action of bismuth drugs. Such studies would be beneficial in rational design of new potential drugs. PMID- 22322155 TI - Learning curves for single-site laparoscopic ovarian surgery. AB - STUDY OBJECTIVE: To compare learning curves for laparoendoscopic single-site surgery (LESS) for ovarian tumors according to the type of procedure (oophorectomy vs cystectomy). DESIGN: A prospective cohort study. (Canadian Task Force Classification II-2). SETTING: University hospital. PATIENTS: One hundred fifteen patients who planned to undergo LESS for ovarian tumors by a surgeon between May 2008 and August 2010. INTERVENTIONS: LESS. MEASUREMENTS AND MAIN RESULTS: The learning curve was assessed through the graph between the operative time and sequence of cases. Proficiency, defined as the point at which the slope of the learning curve became less steep, and surgical outcome were compared between the two surgery groups. LESS was successfully completed in 103 of 115 patients (94.8%). Learning curve for oophorectomies (n = 59) showed a continued slow slope with no apparent proficiency, suggesting oophorectomies did not pose an initial technical challenge. However, proficiency in cystectomies (n = 56) was evident at the thirty-third case. Furthermore, the oophorectomy group had a shorter operative time and less need for additional ports than the cystectomy group (69.4 minutes vs 100.1 minutes; 5.1% vs 14.3%). CONCLUSION: Oophorectomy rather than cystectomy is recommended as the initial procedure to start with LESS for ovarian tumors. PMID- 22322156 TI - Endometrial preparation with estradiol plus dienogest (Qlaira) for office hysteroscopic polypectomy: randomized pilot study. AB - STUDY OBJECTIVE: To estimate the effectiveness of Qlaira for endometrial preparation in women undergoing hysteroscopic polypectomy in the office setting. DESIGN: Randomized clinical pilot study (Canadian Task Force classification II 2). SETTING: Academic research environment. PATIENTS: Seventy-four cycling women undergoing hysteroscopic polypectomy (polyp size <1.5 cm). INTERVENTIONS: Women were randomized to be operated on during the proliferative phase (cycle day 5-7) of a spontaneous cycle (group A) or after 9 to 11 days of Qlaira intake (group B). Polypectomy was performed by using forceps and bipolar electrodes when required. MEASUREMENTS AND MAIN RESULTS: The quality of visualization of the uterine cavity during the procedure (visual analog score [VAS] 0-5, bad to optimal), total surgeon satisfaction (VAS 0-5, very difficult to easy to perform), and total patient satisfaction (VAS 0-5, severe pain to no pain) were compared. Endometrial thickness before and at the end of the procedure was significantly less in women in group B. Mean duration of interventions was shorter in group B than in group A. In addition, vision quality, and surgeon and patient satisfaction rates were significantly higher in women in group B. CONCLUSIONS: At 10 days before surgery, administration of Qlaira is effective for preparation of the endometrium for hysteroscopic polypectomy in the office setting. With preoperative administration of Qlaira, the surgical procedure can be performed more easily and faster, and both surgeon and patient satisfaction rates are improved. PMID- 22322157 TI - Single molecule probes of membrane structure: orientation of BODIPY probes in DPPC as a function of probe structure. AB - Single molecule fluorescence measurements have recently been used to probe the orientation of fluorescent lipid analogs doped into lipid films at trace levels. Using defocused polarized total internal reflection fluorescence microscopy (PTIRF-M), these studies have shown that fluorophore orientation responds to changes in membrane surface pressure and composition, providing a molecular level marker of membrane structure. Here we extend those studies by characterizing the single molecule orientations of six related BODIPY probes doped into monolayers of DPPC. Langmuir-Blodgett monolayers transferred at various surface pressures are used to compare the response from fluorescent lipid analogs in which the location of the BODIPY probe is varied along the length of the acyl chain. For each BODIPY probe location along the chain, comparisons are made between analogs containing phosphocholine and smaller fatty acid headgroups. Together these studies show a general propensity of the BODIPY analogs to insert into membranes with the BODIPY probe aligned along the acyl chains or looped back to interact with the headgroups. For all BODIPY probes studied, a bimodal orientation distribution is observed which is sensitive to surface pressure, with the population of BODIPY probes aligned along the acyl chains increasing with elevated surface pressure. Trends in the single molecule orientations for the six analogs reveal a configuration where optimal placement of the BODIPY probe within the acyl chain maximizes its sensitivity to the surrounding membrane structure. These results are discussed in terms of balancing the effects of headgroup association with acyl chain length in designing the optimal placement of the BODIPY probe. PMID- 22322158 TI - CCND1 G870A polymorphism is associated with increased risk of colorectal cancer, especially for sporadic colorectal cancer and in Caucasians: a meta-analysis. AB - AIMS: To detect the association between G870A polymorphism of cyclin D1 (CCND1) gene and colorectal cancer. METHODS: We performed a systematic literature and abstract search using PubMed, EMBase digital database. Keywords included CCND1, cyclin D1, polymorphism, SNP, colon cancer, rectal cancer and colorectal cancer. "And", "OR" and "NOT" were used as conjunction to narrow and widen the search. Data were extracted by two investigators independently, and meta-analysis was carried out by using Review Manager 4.2.8. The following pairwised combinations of genotypes for the CCND1 G870A polymorphism were evaluated: AA vs. GG, AG vs. GG, AA+AG vs. GG. Subsequently, sub-group analyses for cancer type, ethnicity, and the family history were performed. Sensitivity analysis was conducted by excluding the articles deviated from Hardy-Weinberg equilibrium. RESULTS: Using GG genotype as a reference, A carriers were associated with a significantly increased cancer risk (OR=1.15, 95%CI=1.06-1.25, P=0.001, P(heterogeneity)=0.130), especially with rectal cancer (OR=1.24, 95%CI=1.02-1.51, P=0.030, P(heterogeneity)=0.570) and sporadic colorectal cancer (OR=1.26, 95%CI=1.08-1.46, P=0.003, P(heterogeneity)=0.730). The effect of A carriers on cancer also existed in Caucasians (OR=1.19, 95%CI=1.06-1.32, P=0.002, P(heterogeneity)=0.100). CONCLUSIONS: CCND1 G870A polymorphism is associated with the increased risk of colorectal cancer, especially for sporadic colorectal cancer and in Caucasians. PMID- 22322159 TI - Impact of regulatory perturbations to disease spread through cattle movements in Great Britain. AB - During the past decade the British livestock industry has suffered from several major pathogen outbreaks, and a variety of regulatory and disease control measures have been applied to the movement of livestock with the express aim of mitigating the spread of infection. The Rapid Analysis and Detection of Animal related Risks (RADAR) project, which has been collecting data on the movement of cattle since 1998, provides a relatively comprehensive record of how these policies have influenced the movement of cattle between animal holdings, markets, and slaughterhouses in Britain. Many previous studies have focused on the properties of the network that can be derived from these movements--treating farms as nodes and movements as directed (and potentially weighted) edges in the network. However, of far greater importance is how these policy changes have influenced the potential spread of infectious diseases. Here we use a stochastic fully individual-based model of cattle in Britain to assess how the epidemic potential has varied from 2000 to 2009 as the pattern of movements has changed in response to legislation and market forces. Our simulations show that the majority of policy changes lead to significant decreases in the epidemic potential (measured in multiple ways), but that this potential then increases through time as cattle farmers modify their behaviour in response. Our results suggest that the cattle industry is likely to experience boom-bust dynamics, with the actions that farmers take during epidemic-free periods to maximise their profitability likely to increase the potential for large-scale epidemics to occur. PMID- 22322160 TI - Cataract surgery is refractive surgery. PMID- 22322161 TI - Glued endocapsular hemi-ring segment for fibrin glue-assisted sutureless transscleral fixation of the capsular bag in subluxated cataracts and intraocular lenses. AB - Surgical expertise, prolonged surgical time, suture-related problems, and delayed intraocular lens (IOL) subluxation or dislocation due to broken sutures are limitations of suture fixation of the capsular bag to the scleral wall. We describe a new device made of IOL haptic material (polyvinylidene fluoride) that allows sutureless fibrin glue-assisted transscleral fixation of the capsular bag to address these issues. The device has a hemi-ring portion that lies in the capsular fornix and a double scroll mechanism that engages the capsulorhexis rim. The scroll extends forward as a haptic that is exteriorized through a sclerotomy under a lamellar scleral flap and tucked into a scleral tunnel. The flap is closed with fibrin glue. The device is used for subluxated cataracts and IOLs. It anchors the capsular bag to the sclera, giving vertical and horizontal stability, while providing fornix expansion and allowing stabilization of the bag intraoperatively and postoperatively. The device has been used in 4 patients who had good intraoperative and postoperative courses over a 5-week period. PMID- 22322162 TI - Effect on visual acuity of increased surface light scattering in intraocular lenses. AB - PURPOSE: To assess the long-term increase in surface light scattering of foldable hydrophobic acrylic intraocular lenses (IOLs) and to evaluate its effect on visual acuity. SETTING: Miyata Eye Hospital, Miyazaki, Japan. DESIGN: Cross sectional study. METHODS: The clinical records of patients who received an Acrysof IOL (study group) or a Sensar AR40 or AR40e IOL (control group) were reviewed retrospectively. Surface light scattering of IOLs was measured 1 year postoperatively or later. The corrected distance visual acuity (CDVA) at the surface-light-scattering examination was compared with the CDVA 1 month after IOL implantation. The changes in CDVA over time were compared with the increase in surface light scattering. RESULTS: The study evaluated 466 eyes of 337 patients. Surface light scattering in the study group continued to increase up to 15 years postoperatively. The light scattering was higher on the anterior IOL surface after 4.5 years. Increased surface light scattering had no significant impact on CDVA; however, there were more cases with decreased CDVA when the surface light scattering exceeded 50 computer-compatible tape steps. CONCLUSION: Surface light scattering with the implanted foldable hydrophobic acrylic IOL continuously increased during the postoperative years and was a risk for decreased visual acuity. PMID- 22322163 TI - Visual function comparison of 2 aspheric multifocal intraocular lenses. AB - PURPOSE: To compare visual function after bilateral implantation of the multifocal Lentis Mplus LS-312 with a nonrotational symmetrical design (copolymer aspheric) or the Acrysof Restor SN6AD1 +3.0 D (hybrid aspheric) intraocular lens (IOL). SETTING: Fernandez-Vega Ophthalmological Institute, Oviedo, Spain. DESIGN: Comparative case series. METHODS: Six months postoperatively, corrected distance visual acuity (CDVA), distance-corrected near visual acuity (DCNVA), the defocus curve, and photopic and mesopic contrast sensitivity with and without glare were measured. RESULTS: The mean CDVA was 0.02 +/- 0.06 (SD) with the copolymer aspheric IOL and -0.06 +/- 0.05 logMAR with the hybrid aspheric IOL (P=.07) and the mean DCNVA, 0.10 +/- 0.06 and -0.09 +/- 0.06 logMAR, respectively. The DCNVA was better with the hybrid aspheric IOL (P<.05). The defocus curve showed that the hybrid aspheric IOL provided better visual acuity from 0.00 to -5.00 diopter (D) vergences (P<.05) except for -1.00 and -1.50 D, where the IOLs were comparable. Contrast sensitivity was better with the hybrid aspheric IOL at 12 cycles per degree (cpd) and 18 cpd under photopic conditions (P<.05). No significant differences were found under mesopic conditions (P>.05). CONCLUSIONS: Both IOL models gave good and comparable visual acuity at distance. However, the hybrid aspheric IOL provided better DCNVA than the copolymer aspheric IOL. Intermediate vision was not as good as distance and near and was similar between the 2 IOLs. Photopic contrast sensitivity was better with the hybrid aspheric IOL at high spatial frequencies and comparable between IOLs at low frequencies and under mesopic conditions. PMID- 22322164 TI - Toric collagen copolymer phakic intraocular lens to correct myopic astigmatism in eyes with pellucid marginal degeneration. AB - PURPOSE: To evaluate the clinical outcomes of implantation of the Implantable Collamer Lens collagen copolymer toric phakic intraocular lens (pIOL) to correct myopic astigmatism in eyes with mild pellucid marginal degeneration (PMD). SETTING: Gimbel Eye Centre, Calgary, Alberta, Canada. DESIGN: Retrospective chart review. METHODS: All consecutive cases with PMD that had implantation of the toric pIOL from January 1, 2003, to May 30, 2011, were retrospectively reviewed for postoperative outcomes. Perioperative variables of interest included uncorrected (UDVA) and corrected (CDVA) distance visual acuities, manifest refraction, and corneal topography. RESULTS: The study comprised 10 eyes of 5 patients. The mean age was 37.4 years +/- 2.6 (SEM). The mean CDVA was 0 +/- 0.03 logMAR (20/20) preoperatively and -0.04 +/- 0.03 logMAR (20/18) postoperatively. The mean postoperative UDVA was +0.14 +/- 0.05 logMAR (20/28). The mean spherical equivalent (SE) was -6.71 +/- 0.9 diopters (D) preoperatively and -0.58 +/- 0.1 D at the last follow-up. All eyes had improved CDVA after surgery. One patient reported severe glare and halos in 1 eye postoperatively, requiring removal and replacement of the toric pIOL because of a hyperopic refractive surprise. The new toric pIOL was subsequently repositioned because of high residual astigmatism related to changes in corneal topography postoperatively and a small shift in the position of the toric pIOL. The final manifest refraction for this eye was plano 1.00 * 160. CONCLUSIONS: Implantation of the collagen copolymer toric pIOL was a safe, effective surgical procedure for the correction of myopic astigmatism in eyes with mild PMD. PMID- 22322165 TI - Higher-order aberrations after corneal collagen crosslinking for keratoconus and corneal ectasia. AB - PURPOSE: To determine changes in higher-order aberrations (HOAs) after corneal collagen crosslinking (CXL). SETTING: Cornea and refractive surgery practice. DESIGN: Prospective randomized controlled clinical trial. METHODS: Corneal and ocular HOAs were measured and analyzed using the Pentacam device and Ladarwave aberrometer, respectively, at baseline and 12 months after CXL. RESULTS: Ninety six eyes (64 keratoconus, 32 ectasia) of 73 patients had CXL. A fellow-eye control group comprised 42 eyes. The mean preoperative total anterior corneal HOAs, total coma, 3rd-order coma, and vertical coma were 4.68 MUm +/- 2.33 (SD), 4.40 +/- 2.32 MUm, 4.36 +/- 2.30 MUm, and 4.04 +/- 2.27 MUm, respectively. At 1 year, the mean values decreased significantly to 4.27 +/- 2.25 MUm, 4.01 +/- 2.29 MUm, 3.96 +/- 2.27 MUm, and 3.66 +/- 2.22 MUm, respectively (all P<.001). There were no significant changes in posterior corneal HOAs. The mean preoperative total ocular HOAs, total coma, 3rd-order coma, trefoil, and spherical aberration were 2.80 +/- 1.0 MUm, 2.60 +/- 1.03 MUm, 2.57 +/- 1.03 MUm, 0.98 +/- 0.46 MUm, and 0.90 +/- 0.42 MUm, respectively. At 1 year, the mean values decreased significantly to 2.59 +/- 1.06 MUm, 2.42 +/- 1.07 MUm, 2.39 +/- 1.07 MUm, 0.88 +/ 0.49 MUm, and 0.83 +/- 0.38 MUm, respectively (all P=.01). After CXL, HOAs were significantly improved compared with the control group. Changes in HOAs were not statistically associated with an improvement in visual acuity or most subjective visual symptoms, however. CONCLUSION: Corneal and ocular HOAs decreased after CXL, suggesting an improvement in corneal shape. PMID- 22322166 TI - Ab interno trabeculectomy: outcomes in exfoliation versus primary open-angle glaucoma. AB - PURPOSE: To compare outcomes in exfoliation glaucoma versus primary open-angle glaucoma (POAG) after ab interno trabeculectomy alone (Trabectome) or in combination with cataract surgery and intraocular lens (IOL) implantation. SETTING: Trabectome Study Group institutions. DESIGN: Prospective nonrandomized cohort study. METHODS: Outcomes included intraocular pressure (IOP), glaucoma medications, complications, secondary procedures, and success, defined as no secondary surgery and IOP less than 21 mm Hg and a greater than 20% reduction from baseline. RESULTS: In the ab interno trabeculectomy-alone group, the mean preoperative IOP was 29.0 mm Hg +/- 7.5 (SD) in exfoliation glaucoma cases and 25.5 +/- 7.9 mm Hg in POAG cases (P<.01). At 1 year, the mean decrease in IOP was -12.3 +/- 8.0 mm Hg and -7.5 +/- 7.4 mm Hg, respectively (P<.01); the secondary procedure rate was 20.9% and 34.9%, respectively (P=.02); and the cumulative probability of success was 79.1% and 62.9%, respectively (P=.004). In the combined ab interno trabeculectomy-IOL group, the mean preoperative IOP was 21.7 +/- 8.4 in exfoliation glaucoma cases and 19.9 +/- 5.4 mm Hg in POAG cases (P=.06). At 1 year, the mean decrease in IOP was -7.2 +/- 7.7 and -4.1 +/- 4.6, respectively (P<.01); the secondary procedure rate was 6.7% and 6.1%, respectively (P=.88); and the cumulative probability of success was 86.7% and 91.0% (P=.73), respectively. CONCLUSION: Ab interno trabeculectomy using this new incisional procedure safely lowered IOP to the mid teens, with an overall greater reduction in exfoliation glaucoma and improved success when combined with cataract surgery. PMID- 22322167 TI - Comparison of deep anterior lamellar keratoplasty and intrastromal corneal ring segment implantation in advanced keratoconus. AB - PURPOSE: To compare the visual and refractive results in eyes with advanced keratoconus having deep anterior lamellar keratoplasty (DALK) with those having intrastromal corneal ring segment (ICRS) implantation. SETTING: Dr. Lutfi Kirdar Kartal Training and Research Hospital, Istanbul, Turkey. DESIGN: Comparative case series. METHODS: Records of advanced keratoconus patients with a clear central cornea and contact lens intolerance who had DALK or ICRS implantation were reviewed. Preoperatively and after 24 months, the uncorrected (UDVA) and corrected (CDVA) distance visual acuities, refraction, and Orbscan II keratometry (K) readings in the 2 groups were comparable. RESULTS: The DALK group comprised 36 eyes and the ICRS group, 30 eyes. Both groups had a statistically significant increase in UDVA and CDVA from preoperatively to 24 months postoperatively (P<.001). The DALK group had a statistically significantly greater improvement in UDVA and CDVA than the ICRS group 24 months postoperatively (P<.001). The improvement in spherical equivalent (SE) refractive error, manifest sphere, and manifest cylinder was statistically significant in both groups (P<.001). The mean reduction in SE and manifest cylinder were significantly greater in the DALK group (P<.05). The postoperative reduction in the maximum and minimum K values was statistically significant in both groups (P<.001); the mean reduction in K values was significantly greater in the DALK group (P<.001). CONCLUSION: Although DALK provided greater improvement in visual acuity and refractive errors in advanced keratoconus cases, ICRS implantation may be an alternative treatment with satisfactory outcomes and less visual impact. PMID- 22322168 TI - Stroke dynamics and frequency of 3 phacoemulsification machines. AB - PURPOSE: To measure the working frequency and the stroke dynamics of the phaco tip of 3 phacoemulsification machines. SETTING: University Eye Clinic of Trieste, Italy. DESIGN: Experimental study. METHODS: A video wet fixture was assembled to measure the working frequency using a micro camera and a micropulsed strobe-light system. A different video wet fixture was created to measure tip displacement as vectorial movement at different phaco powers using a microscopic video apparatus. RESULTS: The working frequency of the Infiniti Ozil machine was 43.0 kHz in longitudinal mode and 31.6 kHz in torsional mode. The frequency of the Whitestar Signature machine was 29.0 kHz in longitudinal mode and 38.0 kHz with the Ellips FX handpiece. The Stellaris machine had a frequency of 28.8 kHz. The longitudinal stroke of the 3 machines at different phaco powers was statistically significantly different. The Stellaris machine had the highest stroke extent (139 MUm). The lateral movement of the Infiniti Ozil and Whitestar Signature machines differed significantly. No movement on the y-axis was observed for the Infiniti Ozil machine in torsional mode. The elliptical path of the Ellips FX handpiece had different x and y components at different phaco powers. CONCLUSIONS: The 3 phaco machines performed differently in terms of working frequency and stroke dynamics. The knowledge of the peculiar lateral and elliptical path strokes of Infiniti and Whitestar Signature machines may allow the surgeon to fully use these features for lens removal. PMID- 22322169 TI - Small-incision insertion of artificial iris prostheses. AB - In this interventional case series, a flexible iris prosthesis was implanted in consecutive patients with sight-compromising iris defects. Each prosthesis was injected via a clear corneal microincision as part of a planned combined procedure. Iris insertion was accompanied by cataract removal or implanted using an intraocular lens injector during glaucoma tube shunt placement in a pseudophakic eye. All 4 patients experienced a positive outcome that was visually beneficial. These early cases suggest that with responsible patient selection and appropriate postoperative management, flexible posterior chamber iris implants can be placed successfully, with significant visual benefit, via a corneal microincision in eyes with congenital, traumatic, or uveitic iris defects. PMID- 22322171 TI - Consultation Section. Cataract surgical problem. PMID- 22322180 TI - Role of the phaco tip surface. PMID- 22322182 TI - Internal astigmatism and ocular residual astigmatism. PMID- 22322184 TI - Cognitive intervention in amnestic Mild Cognitive Impairment: a systematic review. AB - Mild Cognitive Impairment (MCI) represents a transitional state between normal aging and early dementia and is commonly associated with memory impairment (amnestic or A-MCI). Several studies have investigated therapeutic approaches to A-MCI, including cholinestherase inhibitors (I-ChEs), although this practice is still controversial. Thus, there is a current need to determine the effects of cognitive interventions either in combination with I-ChEs or alone. To assess the efficacy of such treatments, neuropsychological instruments and self-evaluated scoring of memory, mood, daily life activities and quality of life are employed. Recently, some studies have used functional magnetic resonance imaging (fMRI) in order to understand the neurobiological effects of these interventions. The aim of this systematic review is to investigate the effectiveness of cognitive interventions on the enhancement of learning abilities as well as their impacts on cognitive measurements of mood, everyday functioning and functional neuroimaging. This review also focused on the methodological aspects of such studies and attempted to introduce new perspectives on cognitive interventions in this population. The authors concluded that a-MCI patients are capable to learn new information and memory strategies. Although findings in standardized neuropsychological tests are limited, non-standardized cognitive measures and subjective measures show significant changes. Furthermore, fMRI reveals changes in the patterns of brain activation and increase of connectivity. PMID- 22322185 TI - Crotoxin enhances the antitumor activity of gefinitib (Iressa) in SK-MES-1 human lung squamous carcinoma cells. AB - Crotoxin (CrTX), a neurotoxin, is isolated from the venom of South American rattlesnakes and has potent antitumor activity. Here, we investigated the antitumor effect of CrTX on the SK-MES-1 human lung squamous cell carcinoma cell line that has acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors. CrTX caused G1 arrest and p-JNK protein upregulation that resulted in apoptosis of SK-MES-1 cells. SP600125, a specific inhibitor of p-JNK, could rescue SK-MES-1 cells from CrTX-induced apoptosis. CrTX and gefinitib (Iressa) both inhibited the viability and proliferation of SK-MES-1 cells in a dose- and time-dependent manner. The combination of CrTX and Iressa significantly enhanced the antitumor activity of Iressa. In vivo studies revealed that CrTX caused increased damage to blood vessels and reduced tumor size when combined with Iressa. The present study showed that the JNK signal transduction pathway mediated the anti-apoptotic effect of CrTX, and furthermore, CrTX could enhance the antitumor effect of tyrosine kinase inhibitors in cells with acquired resistance. PMID- 22322186 TI - Measurement for canine IgE using canine recombinant high affinity IgE receptor alpha chain (FcepsilonRIalpha). AB - To detect allergen-specific IgE in dogs with allergic diseases, we developed a recombinant canine high affinity IgE receptor alpha chain (FcepsilonRIalpha) based IgE detection system. Using the recombinant protein of canine FcepsilonRIalpha expressed by an Escherichia coli expression system, we could detect house dust mite (Dermatophagoides farinae) allergen-specific IgE in sera from dogs naturally and experimentally sensitized to this allergen with ELISA and western blotting. The IgE binding activity of recombinant canine FcepsilonRIalpha on ELISA was impaired by heat treatment of these sera. The specificity of this recombinant canine FcepsilonRIalpha-based IgE detection system was confirmed by inhibition assays with canine IgE. The recombinant canine FcepsilonRIalpha-based IgE detection system established in this study offers an alternative tool to measure allergen-specific IgE in dogs. PMID- 22322187 TI - A cytolethal distending toxin gene-based multiplex PCR assay for detection of Campylobacter spp. in stool specimens and comparison with culture method. AB - In this study, we evaluated the applicability of cytolethal distending toxin (cdt) gene-based species-specific multiplex PCR for the direct detection and identification of Campylobacter jejuni, C. coli and C. fetus from stool specimens of patients with gastroenteritis in comparison to culture methods. A total of 711 stool specimens were examined for the isolation or detection of campylobacters by using Skirrow's selective agar culture plates, a filtration method and the multiplex PCR assay. Forty-one and 36 C. jejuni strains were isolated by culture and filtration methods, respectively. In addition, 2 and 3 C. coli strains were isolated by Skirrow and the filtration methods, respectively. However, when the multiplex PCR was employed, the cdtB genes of C. jejuni and C. coli were detected in 45 and 4 stool samples, respectively, and 9 C. jejuni PCR-positive samples by multiplex PCR were negative by culture method. Sequence analysis of the PCR products obtained from 8 stool specimens from which campylobacters were not isolated by culture method but the sequences exactly matched with that of the cdtB gene of C. jejuni strain 81-176. None of the remaining stool samples which were culture negative for campylobacters produced any amplicon. Stool samples were defined as Campylobacter-positive if detected by any method. The sensitivity of the multiplex PCR was 83%, which was higher than Skirrow (74%) and filtration method (66%). These data indicate that cdtB gene-based multiplex PCR is a rapid and more sensitive method to identify the most important species of Campylobacter for human diseases. (248). PMID- 22322188 TI - Canine Lat1: molecular structure, distribution and its expression in cancer samples. AB - A full-length cDNA sequence of canine L-type amino acid transporter 1 (Lat1) was determined from a canine brain. The sequence was 1828 bp long and was predicted to encode 485 amino acid polypeptides. The deduced amino acid sequence of canine Lat1 showed 93.2% and 91.1% similarities to those of humans and rats, respectively. Northern blot analysis detected Lat1 expression in the cerebellum at 4 kb, and Western blot analysis showed a single band at 40 kDa. RT-PCR analysis revealed a distinct expression of Lat1 in the pancreas and testis in addition to the cerebrum and cerebellum. Notably, Lat1 expression was observed in the tissues of thyroid cancer, melanoma and hemangiopericytoma. Although the cancer samples examined were not enough, Lat1 may serve as a useful biomarker of cancer cells in veterinary clinic. PMID- 22322189 TI - A novel vitamin K1 2,3-epoxide reductase (VKOR) inhibitor, 3-acetyl-5 methyltetronic acid, reduces experimental glomerulonephritis. AB - Excessive proliferation of mesangial cells is observed in various types of glomerular disease including glomerulonephritis (GN), which is progressive in nature and eventually results in end-stage renal disease (ESRD). Vitamin K(1) 2,3 epoxide reductase (VKOR) and the vitamin K-dependent growth arrest-specific gene 6/Axl pathway play a key role in mesangial cell proliferation in GN. In the present study, we indicate the potential of a VKOR inhibitor, 3-acetyl-5 methyltetronic acid (AMT), to prevent the proliferation of glomerular mesangial cells and suppress the progression of GN. AMT was administered intravenously to rats once daily for 12 days and a mouse anti-Thy1 monoclonal antibody was injected intravenously after the AMT treatment on Day 6. Creatinine clearance (CCr) significantly increased and the albumin-to-creatinine ratio (ACR) significantly decreased in the AMT-treated group of the Thy-1 GN rats. In addition, glomerular and tubular damage was improved histopathologically in the AMT-treated group. AMT did not affect blood coagulation due to its unique pharmacokinetic properties. The concentration of AMT reached the IC(50) for VKOR in kidney, but not in liver. A novel VKOR inhibitor, AMT, reduced renal mesangial cell proliferation and could be a supportive treatment for GN. PMID- 22322190 TI - BCL2 expression in CD105 positive neoangiogenic cells and tumor progression in angioimmunoblastic T-cell lymphoma. AB - The angiogenic microenvironment has been known to be a component of angioimmunoblastic T-cell lymphoma since its initial characterization. We have shown that angioimmunoblastic T-cell lymphoma endothelial cells produce vascular endothelial growth factor-A (VEGFA), and participate in lymphoma progression. In squamous cell carcinoma, endothelial BCL2 expression induces a crosstalk with tumor cells through VEGFA, a major mediator of tumoral angiogenesis. In the present study, we analyzed BCL2 and VEGFA in 30 angioimmunoblastic T-cell lymphomas, using triple immunofluorescence to identify protein coexpression in well-characterized lymphoma cells and microenvironment neoangiogenic endothelial cells. Using quantitative real-time PCR, we assessed mRNA expression levels in laser-microdissected endothelial and lymphoma cells. In lymphoma cells, as in endothelial cells, BCL2 and VEGFA proteins were coexpressed. BCL2 was expressed only in neoangiogenic CD34(+)CD105(+) endothelial cells. In laser-microdissected cells, mRNA studies showed a significant relationship between BCL2 and VEGFA levels in CD34(+) endothelial cells, but not in CD3(+)CD10(+)lymphoma cells, or in CD34(+) endothelial cells from lymph node hyperplasia. Further study showed that, in AITL, BCL2 mRNA levels in CD34(+)CD105(+) neoangiogenic endothelial cells also correlated with microvessel density, International Prognostic Index, Ann Arbor stage, bone marrow involvement and elevated LDH. BCL2 expression by CD105(+) neoangiogenic endothelial cells is related to tumor progression in angioimmunoblastic T-cell lymphoma. PMID- 22322191 TI - Immunohistochemical testing of conventional adenomas for loss of expression of mismatch repair proteins in Lynch syndrome mutation carriers: a case series from the Australasian site of the colon cancer family registry. AB - Debate continues as to the usefulness of assessing adenomas for loss of mismatch repair protein expression to identify individuals with suspected Lynch syndrome. We tested 109 polyps from 69 proven mutation carriers (35 females and 34 males) belonging to 49 Lynch syndrome families. All polyps were tested by immunohistochemistry for four mismatch repair proteins MLH1, MSH2, MSH6 and PMS2. Detailed pathology review was performed by specialist gastrointestinal pathologists. The majority of polyps (86%) were conventional adenomas (n=94), with 65 tubular and 28 tubulovillous adenomas and a single villous adenoma. The remaining 15 lesions (14%) were serrated polyps. Overall, loss of mismatch repair expression was noted for 78/109 (72%) of polyps. Loss of mismatch repair expression was seen in 74 of 94 (79%) conventional adenomas, and 4 of 15 (27%) serrated polyps from mismatch repair gene mutation carriers. In all instances, loss of expression was consistent with the underlying germline mutation. Mismatch repair protein expression was lost in 27 of 29 adenomas with a villous component compared with 47 of 65 adenomas without this feature (93 vs 73%; P=0.028). A strong trend was observed for high-grade dysplasia. Mismatch repair deficiency was observed in 12 of 12 conventional adenomas with high-grade dysplasia compared with 60 of 79 with low-grade dysplasia (100 vs 76%; P=0.065). We were unable to demonstrate a significant association between conventional adenoma size or site and mismatch repair deficiency. All (4/4 or 100%) of the serrated polyps demonstrating mismatch repair deficiency were traditional serrated adenomas from a single family. Diagnostic testing of adenomas in suspected Lynch syndrome families is a useful alternative in cases where cancers are unavailable. The overwhelming majority of conventional adenomas from mutation carriers show loss of mismatch repair protein expression concordant with the underlying germline mutation. PMID- 22322192 TI - Exploring the unfolding mechanism of gamma-glutamyltranspeptidases: the case of the thermophilic enzyme from Geobacillus thermodenitrificans. AB - gamma-glutamyltranspeptidases (gamma-GTs) are ubiquitous enzymes that catalyze the hydrolysis of gamma-glutamyl bonds in glutathione and glutamine and the transfer of the released gamma-glutamyl group to amino acids or short peptides. These enzymes are generally synthesized as precursor proteins, which undergo an intra-molecular autocatalytic cleavage yielding a large and a small subunit. In this study, circular dichroism and intrinsic fluorescence measurements have been used to investigate the structural features and the temperature- and guanidinium hydrochloride (GdnHCl)-induced unfolding of the mature form of the gamma-GT from Geobacillus thermodenitrificans (GthGT) and that of its T353A mutant, which represents a mimic of the precursor protein. Data indicate that a) the mutant and the mature GthGT have a different secondary structure content and a slightly different exposure of hydrophobic regions, b) the thermal unfolding processes of both GthGT forms occur through a three-state model, characterized by a stable intermediate species, whereas chemical denaturations proceed through a single transition, c) both GthGT forms exhibit remarkable stability against temperature, but they do not display a strong resistance to the denaturing action of GdnHCl. These findings suggest that electrostatic interactions significantly contribute to the protein stability and that both the precursor and the mature form of GthGT assume compact and stable conformations to resist to the extreme temperatures where G. thermodenidrificans lives. Owing to its thermostability and unique catalytic properties, GthGT is an excellent candidate to be used as a glutaminase in food industry. PMID- 22322193 TI - Interfacial modification of organic photovoltaic devices by molecular self organization. AB - This feature article focuses on the relationship between the interfacial structures constructed by molecular self-organization and the properties of organic photovoltaic devices. The use of self-assembled monolayers (SAMs) is reviewed for metal and metal oxide/organic interfaces, while surface-segregated monolayers (SSMs) are introduced as a new method for the modification of organic/organic interfaces. Research up to now has clearly demonstrated the effectiveness of the control of energy levels and other properties at the interfaces to enhance photovoltaic performance. The possibility of more precise control of the interfacial structures is also discussed. PMID- 22322194 TI - Does a nondipping pattern impact the right ventricle in hypertensive patients? AB - OBJECTIVE: The purpose of this study was to determine the influence of a nondipping arterial blood pressure pattern on the right ventricular (RV) structure, diastolic, and global function in recently diagnosed hypertensive patients. METHODS: This cross-sectional study included 189 recently diagnosed hypertensive patients. All participants underwent 24 h ambulatory blood pressure monitoring and a complete two-dimensional echocardiography examination. We determined the ratio of early diastolic transtricuspid and septal areas of the tricuspid annulus flow velocities (E/e')t, as well as appropriate time intervals for the estimation of the Tei index. RV hypertrophy was defined by RV wall thickness of at least 6.0 mm in men and at least 5.5 mm in women. RESULTS: The dipping blood pressure pattern was found in 107 (57%) participants, whereas the nondipping pattern was present in 82 (43%) hypertensive patients. The RV wall thickness as well as the (E/e')t ratio (5.12 +/- 1.03 vs. 5.81 +/- 1.12, P < 0.001) and the RV Tei index (0.42 +/- 0.08 vs. 0.48 +/- 0.11, P < 0.001) were increased in the nondippers (4.2 +/- 0.84 vs. 4.7 +/- 0.87 mm, P < 0.001). Analyses revealed that 24 h, daytime, and night-time systolic blood pressure, the nondipping status, and the left ventricular mass index were independently associated with RV wall thickness (P < 0.001 for all). The same parameters, along with RV wall thickness, were identified as independent predictors of RV diastolic function [(E/e')t] and RV global function (RV Tei index), respectively. CONCLUSION: RV structure, diastolic, and global functions were significantly impaired in nondipper hypertensive patients. A nondipping blood pressure pattern represents one of the independent predictors of RV diastolic and global function as well as RV hypertrophy. PMID- 22322195 TI - Effects of isometric handgrip training on blood pressure (resting and 24 h ambulatory) and heart rate variability in medicated hypertensive patients. AB - OBJECTIVES: Isometric handgrip (IHG) training (four, 2-min sustained contractions at 30% of maximal voluntary contraction, three times per week for 8-10 weeks) lowers resting arterial blood pressure (BP) in hypertensive patients, including those receiving pharmacotherapy, although the mechanisms remain elusive. Ambulatory BP measurements are more efficacious in predicting cardiovascular disease-related events, yet the effects of IHG training on ambulatory BP are unknown. The objective of the current investigation was to test the hypotheses that 8 weeks of IHG training lowers resting and 24 h ambulatory BP concomitantly in medicated hypertensive patients, and may be the result of improved vagal modulation. METHODS: BP was assessed using brachial artery oscillometry, and coarse-graining spectral analysis was used to determine spectral power. Resting and 24 h ambulatory BP and heart rate variability (HRV) were measured pretraining, midtraining, and post-training in 11 medicated hypertensive patients (mean +/- SD, resting BP: 113.9 +/- 12.7/60.7 +/- 11.6 mmHg), and in nine medicated hypertensive controls (resting BP: 117.8 +/- 14.3/67.5 +/- 4.2 mmHg). RESULTS: Indices of BP and HRV were not significantly altered with IHG training (all P > 0.05). CONCLUSION: IHG training does not lower resting or ambulatory BP in hypertensive patients successfully treated with pharmacotherapy to within the normal range (<= 120/80 mmHg), nor does it improve HRV. Future studies should examine alternative IHG training protocols in well-managed hypertensive patients and/or target poorly controlled medicated hypertensive patients. PMID- 22322196 TI - Polycaprolactone electrospun mesh conjugated with an MSC affinity peptide for MSC homing in vivo. AB - Mesenchymal stem cell (MSC) is a promising cell source candidate in tissue engineering (TE) and regenerative medicine. However, the inability to target MSCs in tissues of interest with high efficiency and engraftment has become a significant barrier for MSC-based therapies. The mobilization and transfer of MSCs to defective/damaged sites in tissues or organs in vivo with high efficacy and efficiency has been a major concern. In the present study, we identified a peptide sequence (E7) with seven amino acids through phage display technology, which has a high specific affinity to bone marrow-derived MSCs. Subsequent analysis suggested that the peptide could efficiently interact specifically with MSCs without any species specificity. Thereafter, E7 was covalently conjugated onto polycaprolactone (PCL) electrospun meshes to construct an "MSC-homing device" for the recruitment of MSCs both in vitro and in vivo. The E7-conjugated PCL electrospun meshes were implanted into a cartilage defect site of rat knee joints, combined with a microfracture procedure to mobilize the endogenous MSCs. After 7 d of implantation, immunofluorescence staining showed that the cells grown into the E7-conjugated PCL electrospun meshes yielded a high positive rate for specific MSC surface markers (CD44, CD90, and CD105) compared with those in arginine-glycine-aspartic acid (RGD)-conjugated PCL electrospun meshes (63.67% vs. 3.03%; 59.37% vs. 2.98%; and 61.45% vs. 3.82%, respectively). Furthermore, the percentage of CD68 positive cells in the E7-conjugated PCL electrospun meshes was much lower than that in the RGD-conjugated PCL electrospun meshes (5.57% vs. 53.43%). This result indicates that E7-conjugated PCL electrospun meshes absorb much less inflammatory cells in vivo than RGD-conjugated PCL electrospun meshes. The results of the present study suggest that the identified E7 peptide sequence has a high specific affinity to MSCs. Covalently conjugating this peptide on the synthetic PCL mesh significantly enhanced the MSC recruitment of PCL in vivo. This method provides a wide range of potential applications in TE. PMID- 22322197 TI - The movement of self-assembled amphiphilic polymeric nanoparticles in the vitreous and retina after intravitreal injection. AB - The purpose of this study is to determine the correlation between the distribution of nanoparticles in the vitreous and retina and their surface properties after intravitreal injection. For this purpose, we synthesized seven kinds of nanoparticles through self-assembly of amphiphilic polymer conjugates in aqueous condition. They showed similar size but different surface properties. They were labeled with fluorescent dyes for efficient tracking. After intravitreal injection of these nanoparticles into a rodent eye, their time dependent distribution in the vitreous and retina was determined in stacking tissue images by confocal microscopy. The results demonstrated that the surface property of nanoparticles is a key factor in determining their distribution in the vitreous and retina after intravitreal injection. In addition, immunohistochemistry and TEM images of retina tissues suggested the important mechanism related with Mulller cells for intravitreally administered nanoparticles to overcome the physical barrier of inner limiting membrane and to penetrate into the deeper retinal structures. Therefore, we expect that this study can provide valuable information for biomedical researchers to develop optimized nanoparticles as drug or gene carriers for retinal and optic nerve disorders such as glaucoma, age-related macular degeneration, and diabetic retinopathy. PMID- 22322198 TI - Specific VEGF sequestering and release using peptide-functionalized hydrogel microspheres. AB - Growth factor signaling plays an essential role in regulating processes such as tissue development, maintenance, and repair. Gene expression levels, diffusion, degradation, and sequestration by extracellular matrix components all play a role in regulating the concentration of growth factors within the cellular microenvironment. Herein, we describe the synthesis and characterization of hydrogel microspheres that mimic the ability of the native extracellular matrix to reversibly bind vascular endothelial growth factor (VEGF) out of solution. A peptide ligand derived from the VEGF receptor 2 (VEGFR2) was covalently incorporated into the hydrogel microspheres in order to achieve binding affinity and specificity. In addition to being able to both bind and release VEGF in a controllable manner, the microspheres were also shown to affect human umbilical vein endothelial cell (HUVEC) proliferation. The resulting microspheres may enable new strategies to specifically upregulate or downregulate growth factor signaling in the cellular microenvironment. PMID- 22322199 TI - Target delivery of a gene into the brain using the RVG29-oligoarginine peptide. AB - The development of non-viral delivery systems that are capable of mediating an efficient, exclusive, and non-invasive transfer of DNA across the blood-brain barrier into the brain is challenging, but essential for the clinical application of gene therapy to brain diseases. Compared with other non-viral DNA carriers (e.g., lipids or polymers), peptide-based DNA delivery systems have many advantages including the ease of synthesis, low immunogenicity, biocompatibility, and biodegradability in vivo. However, all of the existing peptide-based vehicles for DNA delivery lack selectivity toward cells or tissues, which largely limited their applications in vivo. In this study, we demonstrated that an RVG29-9rR peptide-based DNA delivery system was able to transfect Neuro 2a cells in vitro more efficiently and specifically than Lipofectamine LTX & Plus, one of the most efficient commercially available transfection reagents. More significantly, the peptide mediated efficient and brain-targeting reporter gene expression after intravenous injection into mice. Thus, the results herein suggest a new strategy for brain-targeting DNA delivery in vivo. PMID- 22322200 TI - Predicting the effects of frameshifting indels. AB - Each human has approximately 50 to 280 frameshifting indels, yet their implications are unknown. We created SIFT Indel, a prediction method for frameshifting indels that has 84% accuracy. The percentage of human frameshifting indels predicted to be gene-damaging is negatively correlated with allele frequency. We also show that although the first frameshifting indel in a gene causes loss of function, there is a tendency for the second frameshifting indel to compensate and restore protein function. SIFT Indel is available at http://sift-dna.org/www/SIFT_indels2.html. PMID- 22322201 TI - Molecular profile of organ culture-stored corneal epithelium: LGR5 is a potential new phenotypic marker of residual human corneal limbal epithelial stem cells. AB - Long-term preservation of corneal limbal epithelium may decrease its quality and change the molecular signature of the limbal epithelial stem cells. In this study we have investigated the molecular profile of isolated corneal epithelial cells that have been in storage for an extended time. Isolated cells were characterised by the expression profile of different cytokeratins and markers of squamous metaplasia (vimentin and alpha-actin). Furthermore, we examined global markers of adult stem cells including p63alpha and ABCG2 but also LGR5 as a novel stem cell marker. Immunocytochemical staining and PCR analysis of p63alpha, ABCG2 and LGR5 revealed the existence of side-population cells with a stem-cell phenotype and maintenance of corneal limbal stem cell properties. LGR5 expression can be related to cellular stemness and can be considered as a new phenotypic marker of residual human corneal limbal stem cells. However, the existence of CK10 together with co-expressed alpha-actin and vimentin suggests that the corneas investigated were under oxidative stress and showed evidence of squamous metaplasia. PMID- 22322202 TI - Modeling of a carbon nanotube ultracapacitor. AB - The modeling of carbon nanotube ultracapacitor (CNU) performance based on the simulation of electrolyte ion motion between the cathode and the anode is described. Using a molecular dynamics (MD) approach, the equilibrium positions of the electrode charges interacting through the Coulomb potential are determined, which in turn yield the equipotential surface and electric field associated with the capacitor. With an applied ac voltage, the current is computed based on the nanotube and electrolyte particle distribution and interaction, resulting in the frequency-dependent impedance Z(omega). From the current and impedance profiles, the Nyquist and cyclic voltammetry (CV) plots are then extracted. The results of these calculations compare well with existing experimental data. A lumped-element equivalent circuit for the CNU is proposed and the impedance computed from this circuit correlates well with the simulated and measured impedances. PMID- 22322203 TI - Comparison of scanning laser ophthalmoscopy and high-definition optical coherence tomography measurements of optic disc parameters. AB - OBJECTIVE: To investigate the agreement between scanning laser ophthalmoscopy (Heidelberg retinal tomograph 3; HRT-3) and high-definition optical coherence tomography (HD-OCT) for measurements of optic nerve head (ONH) parameters. METHODS: As part of a population-based cross-sectional study, 913 consecutive Chinese subjects aged 40 years and older underwent HRT-3 and HD-OCT imaging of the ONH after pupillary dilation. Limits of agreement (LOA) derived from Bland Altman analysis were calculated for ONH measurements. RESULTS: The mean age (+/- SD) of study participants was 54.2 +/- 7.2 years and 52.0% were men. The two instruments showed no difference in mean optic disc area measurements (1.98 +/- 0.37 for HD-OCT vs 1.98 +/- 0.39 mm for HRT-3, p=0.95). HD-OCT showed smaller rim area (1.29 +/- 0.24 vs 1.46 +/- 0.27 mm, p<0.001), but bigger cup-related parameters (p<0.001 for all) than HRT-3. The highest correlations between the instruments were observed for cup volume (r(2)=0.74, p<0.001) and disc area (r(2)=0.62, p<0.001). The correlations for cup-to-disc ratio (CDR), vertical CDR and rim area were lower (r(2)=0.59, 0.48 and 0.24, respectively, p<0.001 for all). The Bland-Altman plots demonstrated significant proportional bias for differences in all ONH parameters (p<0.01 for all), with LOA greater for disc related parameters (0.98-1.0) than cup-related parameters (0.26-0.50). CONCLUSIONS: There are substantial disagreements between HRT-3 and HD-OCT in ONH measurements. Although optic disc area measurements were similar, HD-OCT underestimates the rim area and overestimates cup parameters compared with HRT-3. PMID- 22322204 TI - Predictive factors that influence treatment outcomes of innovative single incision sling: comparing TVT-Secur to an established transobturator sling for female stress urinary incontinence. AB - INTRODUCTION AND HYPOTHESIS: This study aims to identify independent risk factors for treatment failure of tension-free vaginal tape TVT-Secur (TVT-S) compared to that of the well-established transobturator tape. MATERIALS AND METHODS: Of a total of 175 consecutive patients with urodynamically confirmed stress urinary incontinence (SUI) identified between July 2007 and March 2010, 89 patients underwent TVT-S, and 86 underwent TOT. Cure was defined using the Urogenital Distress Inventory as no urinary leakage during physical activity, coughing, or sneezing as reported by patients during a telephone survey. To identify predictors of treatment failure, multivariable logistic regression models were used, and odds ratios (ORs) were calculated using variables identified during univariate analysis. RESULTS: There were more patients with cystocele >= grade 2 in the TVT-S group (p = 0.031); otherwise the groups were well matched. After a median follow-up of 32 months (range, 12-44 months), the overall cure rate was 80.6%; it was 70.8% for those treated with TVT-S and 90.7% for those treated with TOT (p = 0.001). In a multivariate model, previous incontinence surgery (OR 27.1, p = 0.005) and a cystocele >= grade 2 (OR 3.0, p = 0.020) were independent risk factors influencing the outcome of TVT-S procedures. For the TOT procedures, detrusor overactivity was an independent risk factor in a multivariate model (OR 8.6, p = 0.033). CONCLUSIONS: TVT-S could be performed for selected patients, but conventional TOT procedures are still superior to the novel TVT-S device. PMID- 22322205 TI - Isomorphic phenomenon in discoid lupus erythematosus with review of reported cases. PMID- 22322206 TI - Parameters related to a positive test result for FDG PET(/CT) for large vessel vasculitis: a multicenter retrospective study. AB - The purpose of this study was to identify clinical and laboratory parameters that may improve the effectiveness of the use of fluorodeoxyglucose positron emission tomography ((18)F-FDG PET)(/CT) for diagnosing large vessel vasculitis (LVV), and secondarily to assess the contribution of (18)F-FDG PET/CT in finding other diagnoses for patients without signs of LVV on the scan. A multicenter retrospective study of (18)F-FDG PET(/CT) scans performed between January 2000 and December 2009 for clinical suspicion of LVV was conducted. A total of 304 (18)F-FDG PET(/CT) scans were included, of which 62 (20%) were positive and 242 (80%) were negative for LVV. Univariate analysis showed that patients with a positive scan were older (65.9 +/- 13.4 versus 58.6 +/- 16.5 years, p = 0.002), were more frequently female (76% versus 55%, p = 0.002), more often had a history of temporal arteritis (10% versus 3%, p = 0.044), less frequently had artralgia (31% versus 67%, p = 0.000), and had higher thrombocyte counts (434 +/- 161 versus 373 +/- 168 * 10(9)/l, p = 0.049) and a higher erythrocyte sedimentation rate (ESR) (72.6 +/- 31.0 versus 51.4 +/- 30.5 mm/h, p = 0.001) than patients with a negative scan. In the multivariate analysis, only artralgia (OR 0.091; 95% CI 0.023-0.366) and ESR (OR 1.024; 95% CI 1.002-1.046) remained statistically significant predictors. The presence of artralgia is a statistically significant negative predictor and an elevated ESR a statistically significant positive predictor of LVV showing up on (18)F-FDG PET(/CT). A reliable prediction of the outcome of the scan, based on these two parameters, is not possible however. (18)F-FDG PET(/CT) allows early diagnosis of LVV and may discover occult inflammatory or neoplastic disorders. PMID- 22322207 TI - Correlation of serum CX3CL1 level with disease activity in adult-onset Still's disease and significant involvement in hemophagocytic syndrome. AB - To investigate the characteristics of patients with adult-onset Still's disease (AOSD), serum cytokines and chemokines were measured to examine their associations with systemic manifestations of AOSD, especially hemophagocytic syndrome (HPS). Nineteen patients diagnosed with AOSD were enrolled. Serial serum samples were obtained from patients with AOSD in both active and inactive stages and controls. The concentrations of cytokines and chemokines, including IL-18, soluble IL-2 receptor (sIL-2R), CX3CL1, CXCL8, CXCL10, CCL2, and CCL3, were determined using enzyme-linked immunosorbent assay. Multivariate analysis was used to evaluate the correlations among serum chemokine levels, disease activity, and the clinical features of AOSD. Significantly higher serum levels of all cytokines and chemokines were observed in patients with active, untreated AOSD than in controls. The level of CX3CL1, but not other chemokines, was elevated in AOSD patients and was positively correlated with clinical activity and the levels of CRP, ferritin, IL-18, and sIL-2R. Among the 19 patients with AOSD, four patients also had HPS. Serum CX3CL1 and ferritin were significantly higher in AOSD patients with HPS than in those without HPS. The serum CX3CL1 level may be used as a clinical marker to assess the disease activity of AOSD, and high serum CX3CL1 and ferritin in patients with AOSD reflected the presence of HPS. The association between the chemokine profile and distinct clinical manifestations or various patterns of disease progression indicates that the pathogenesis of AOSD is heterogeneous. PMID- 22322208 TI - Constant size, variable density aerosol particles by ultrasonic spray freeze drying. AB - This work provides a new understanding of critical process parameters involved in the production of inhalation aerosol particles by ultrasonic spray freeze drying to enable precise control over particle size and aerodynamic properties. A series of highly porous mannitol, lysozyme, and bovine serum albumin (BSA) particles were produced, varying only the solute concentration in the liquid feed, c(s), from 1 to 5 wt%. The particle sizes of mannitol, BSA, and lysozyme powders were independent of solute concentration, and depend only on the drop size produced by atomization. Both mannitol and lysozyme formulations showed a linear relationship between the computed Fine Particle Fraction (FPF) and the square root of c(s), which is proportional to the particle density, rho, given a constant particle size d(g). The FPF decreased with increasing c(s) from 57.0% to 16.6% for mannitol and 44.5% to 17.2% for lysozyme. Due to cohesion, the BSA powder FPF measured by cascade impaction was less than 10% and independent of c(s). Ultrasonic spray freeze drying enables separate control over particle size, d(g), and aerodynamic size, d(a) which has allowed us to make the first experimental demonstration of the widely accepted rule d(a)=d(g)(rho/rho(o))(1/2) with particles of constant d(g), but variable density, rho (rho(o) is unit density). PMID- 22322209 TI - Molecular modelling and multisimplex optimization of tocotrienol-rich self emulsified drug delivery systems. AB - The objective of this study was to optimize a novel tocotrienol (TRF)-rich self emulsified drug delivery system (SEDDS). In the first part, an unusual phenomenon was investigated. It was observed that by substituting Tween 80 with Cremophor EL in the SEDDS it was possible to emulsify>55% TRF (by weight of the formulation) into submicron (<200 nm) emulsion. With Tween, only 17.5% of the loaded TRF could be emulsified into crude emulsion. The superiority of Cremophor was attributed to the special arrangement of the surfactant at the oil/water interface, which was confirmed by modelling and docking studies. In the second part of this study, the composition of the secondary ingredients in the TRF-rich SEDDS were optimized by the modified Multisimplex approach. SEDDS were manufactured at pre-defined step size and tested for their dissolution behavior. Testing was performed sequentially until the optimum composition that can emulsify 50% of the loaded TRF into a stable<150 nm submicron emulsion was obtained. Optimization end-point was identified when the "membership value" approached 1, which was confirmed by a second Multisimplex run. Overall, this study demonstrated the utility of docking studies and the Multisimplex approach in product development when little is known about the experimental "design space". PMID- 22322210 TI - Hemocompatibility of poly(E-caprolactone) lipid-core nanocapsules stabilized with polysorbate 80-lecithin and uncoated or coated with chitosan. AB - The hemocompatibility of nanoparticles is of critical importance for their systemic administration as drug delivery systems. Formulations of lipid-core nanocapsules, stabilized with polysorbate 80-lecithin and uncoated or coated with chitosan (LNC and LNC-CS), were prepared and characterized by laser diffraction (D[4,3]: 129 and 134 nm), dynamic light scattering (119 nm and 133 nm), nanoparticle tracking (D50: 124 and 139 nm) and particle mobility (zeta potential: -15.1 mV and +9.3 mV) analysis. In vitro hemocompatibility studies were carried out with mixtures of nanocapsule suspensions in human blood at 2% and 10% (v/v). The prothrombin time showed no significant change independently of the nanocapsule surface potential or its concentration in plasma. Regarding the activated partial thromboplastin time, both suspensions at 2% (v/v) in plasma did not influence the clotting time. Even though suspensions at 10% (v/v) in plasma decreased the clotting times (p<0.05), the values were within the normal range. The ability of plasma to activate the coagulation system was maintained after the addition of the formulations. Suspensions at 2% (v/v) in blood showed no significant hemolysis or platelet aggregation. In conclusion, the lipid-core nanocapsules uncoated or coated with chitosan are hemocompatible representing a potential innovative nanotechnological formulation for intravenous administration. PMID- 22322211 TI - Preparation of E-selectin-targeting nanoparticles and preliminary in vitro evaluation. AB - Targeted delivery aims to concentrate therapeutic agents at their site of action and thereby enhance treatment and limit side-effects. E-selectin on endothelial cells is markedly up-regulated by cytokine stimulation of inflamed and some tumoral tissues, promoting the adhesion of leukocytes and metastatic tumor cells, thus making it an interesting molecular target for drug delivery systems. We report here the preparation of targeted nanoparticles from original amphiphilic block copolymers functionalized with an analog of sialyl Lewis X (SLEx), the physiological ligand of E-selectin. Nanoparticles, prepared by nanoprecipitation, caused no significant cytotoxicity. Ligand-functionalized nanoparticles were specifically recognized and internalized better by tumor necrosis factor alpha (TNF-alpha)-activated human umbilical vein endothelial cells (HUVECs) than control nanoparticles or HUVECs with low E-selectin expression. These nanoparticles are designed to carry the ligand at the end of a PEG spacer to improve accessibility. This system has potential for the treatment of inflammation, inhibition of tumor metastasis, and for molecular imaging. PMID- 22322213 TI - Tremor, olfactory and motor changes in Italian adolescents exposed to historical ferro-manganese emission. AB - BACKGROUND AND OBJECTIVE: Increased prevalence of Parkinsonism was observed in Valcamonica, Italy, a region impacted by ferroalloy plants emissions containing manganese and other metals for a century until 2001. The aim of this study was to assess neurobehavioral functions in adolescents from the impacted region and the reference area of Garda Lake. METHODS: Adolescents age 11-14 years were recruited through the school system for neuro-behavioral testing. Metals including manganese, lead, iron, zinc, copper were measured in airborne particulate matter collected with 24-h personal samplers, and in soil, tap water, blood, urine and hair. Independent variables included parental education and socio-economic status, children's body mass index, number of siblings, parity order, smoking and drinking habits. RESULTS: A total of 311 subjects (49.2% females), residing in either the exposed (n=154) or the reference (n=157) area participated. Average airborne and soil manganese were respectively 49.5 ng/m(3) (median 31.4, range 1.24-517) and 958 ppm (median 897, range 465-1729) in the impacted area, and 27.4 ng/m(3) (median 24.7, range 5.3-85.9) ng/m(3) and 427 ppm (median 409 range 160 734) in the reference area. Regression models showed significant impairment of motor coordination (Luria-Nebraska test, p=0.0005), hand dexterity (Aiming Pursuit test, p=0.0115) and odor identification (Sniffin' task, p=0.003) associated with soil manganese. Tremor intensity was positively associated with blood (p=0.005) and hair (p=0.01) manganese. CONCLUSION: Historical environmental exposure to manganese from ferroalloy emission reflected by the concentration in soil and the biomarkers was associated with sub-clinical deficits in olfactory and motor function among adolescents. PMID- 22322212 TI - Microglia in the developing brain: a potential target with lifetime effects. AB - Microglia are a heterogenous group of monocyte-derived cells serving multiple roles within the brain, many of which are associated with immune and macrophage like properties. These cells are known to serve a critical role during brain injury and to maintain homeostasis; yet, their defined roles during development have yet to be elucidated. Microglial actions appear to influence events associated with neuronal proliferation and differentiation during development, as well as, contribute to processes associated with the removal of dying neurons or cellular debris and management of synaptic connections. These long-lived cells display changes during injury and with aging that are critical to the maintenance of the neuronal environment over the lifespan of the organism. These processes may be altered by changes in the colonization of the brain or by inflammatory events during development. This review addresses the role of microglia during brain development, both structurally and functionally, as well as the inherent vulnerability of the developing nervous system. A framework is presented considering microglia as a critical nervous system-specific cell that can influence multiple aspects of brain development (e.g., vascularization, synaptogenesis, and myelination) and have a long term impact on the functional vulnerability of the nervous system to a subsequent insult, whether environmental, physical, age-related, or disease-related. PMID- 22322214 TI - Early tracheostomy decreases ventilation time but has no impact on mortality of intensive care patients: a randomized study. AB - BACKGROUND: Long-term ventilation in intensive care units (ICUs) is associated with several problems such as increased mortality, increased rates of ventilator associated pneumonia (VAP), and prolonged time of hospitalization, and thus leads to enormous healthcare expenditure. While the influence of tracheostomy on VAP incidence, duration of ventilation, and time of hospitalization has already been analyzed in several studies, the timing of the tracheostomy procedure on patient's mortality is still controversial. The aim of our study was to investigate whether early tracheostomy improved outcome in critically ill patients. MATERIALS AND METHODS: Within 2 years, 100 critically ill, predominantly surgical patients entered this prospective randomized study. A percutaneous dilatational tracheostomy was performed either early (<=4 days, 2.8 days median) or late (>=6 days, 8.1 days median) after intubation. RESULTS: We could demonstrate that mortality was not significantly reduced in the early tracheostomy (ET) group in contrast to the late tracheostomy (LT) group. ET was associated with decreased VAP incidence (ET 38% vs. LT 64%), decreased duration of ventilation (ET 367.5 h vs LT 507.5 h), and shorter time of hospitalization both in hospital (ET 31.5 days vs LT 68 days) and in ICU (ET 21.5 days vs LT 27 days). CONCLUSION: Despite many advantages like reduced time of ventilation and hospitalization, early tracheostomy is not associated with decreased mortality in critically ill patients. PMID- 22322215 TI - Whole-mount three-dimensional imaging of internally localized immunostained cells within mouse embryos. AB - We describe a three-dimensional (3D) confocal imaging technique to characterize and enumerate rare, newly emerging hematopoietic cells located within the vasculature of whole-mount preparations of mouse embryos. However, the methodology is broadly applicable for examining the development and 3D architecture of other tissues. Previously, direct whole-mount imaging has been limited to external tissue layers owing to poor laser penetration of dense, opaque tissue. Our whole-embryo imaging method enables detailed quantitative and qualitative analysis of cells within the dorsal aorta of embryonic day (E) 10.5 11.5 embryos after the removal of only the head and body walls. In this protocol we describe the whole-mount fixation and multimarker staining procedure, the tissue transparency treatment, microscopy and the analysis of resulting images. A typical two-color staining experiment can be performed and analyzed in ~6 d. PMID- 22322216 TI - Synthesis of N-methylated cyclic peptides. AB - This protocol presents a detailed description of the synthesis of N-methylated cyclic peptides. N-methylation is a powerful technique to modulate the physicochemical properties of peptides by introducing one or more methyl groups into the peptidic amide bonds. Together with peptide cyclization, this procedure confers unprecedented pharmacokinetic properties to the peptides, including metabolic stability, membrane permeability and even oral bioavailability. Here we describe two simplified methods of N-methylation of linear peptides on solid supports, which can be performed in less than 2 h and are applicable to any amino acid. Finally, we also describe two methods of peptide cyclization, which can be used to obtain the N-methylated cyclic peptide and which are not limited to specific peptide sequences. With this protocol, multiply N-methylated cyclic peptides can be synthesized in as little as 4-5 d. PMID- 22322217 TI - Single-molecule pull-down for studying protein interactions. AB - This protocol describes a single-molecule pull-down (SiMPull) assay for analyzing physiological protein complexes. The assay combines the conventional pull-down assay with single-molecule total internal reflection fluorescence (TIRF) microscopy and allows the probing of single macromolecular complexes directly from cell or tissue extracts. In this method, antibodies against the protein of interest are immobilized on a passivated microscope slide. When cell extracts are applied, the surface-tethered antibody captures the protein together with its physiological interaction partners. After washing away the unbound components, single-molecule fluorescence microscopy is used to probe the pulled-down proteins. Captured proteins are visualized through genetically encoded fluorescent protein tags or through antibody labeling. Compared with western blot analysis, this ultrasensitive assay requires considerably less time and reagents and provides quantitative data. Furthermore, SiMPull can distinguish between multiple association states of the same protein. SiMPull is generally applicable to proteins from a variety of cellular contexts and to endogenous proteins. Starting with the cell extracts and passivated slides, the assay requires 1.5-2.5 h for data acquisition and analysis. PMID- 22322218 TI - Overexpressing human membrane proteins in stably transfected and clonal human embryonic kidney 293S cells. AB - X-ray crystal structures of human membrane proteins, although potentially of extremely great impact, are highly underrepresented relative to those of prokaryotic membrane proteins. One key reason for this is that human membrane proteins can be difficult to express at a level, and at a quality, suitable for structural studies. This protocol describes the methods that we use to overexpress human membrane proteins from clonal human embryonic kidney 293 (HEK293S) cells lacking N-acetylglucosaminyltransferase I (GnTI(-)), and was recently used in our 2.1-A X-ray crystal structure determination of human RhCG. Upon identification of highly expressing cell lines, suspension cell cultures are scaled up in a facile manner either using spinner flasks or cellbag bioreactors, resulting in a final purified yield of ~0.5 mg of membrane protein per liter of medium. The protocol described here is reliable and cost effective, can be used to express proteins that would otherwise be toxic to mammalian cells and can be completed in 8-10 weeks. PMID- 22322219 TI - Enemies maintain hyperdiverse tropical forests. AB - Understanding tropical forest tree diversity has been a major challenge to ecologists. In the absence of compensatory mechanisms, two powerful forces, drift and competition, are expected to erode diversity quickly, especially in communities containing scores or hundreds of rare species. Here, I review evidence bearing on four compensatory mechanisms that have been subsumed under the terms "density dependence" or "negative density dependence": (1) intra- and (2) interspecific competition and the action of (3) density-responsive and (4) distance-responsive biotic agents, as postulated by Janzen and Connell. To achieve ontological integration, I examine evidence based on studies employing seeds, seedlings, and saplings. Available evidence points overwhelmingly to the action of both host-generalist and host-restricted biotic agents as causing most seed and seedling mortality, implying that species diversity is maintained via top-down forcing. The overall effect of most host-generalist seed predators and herbivores is to even out the distribution of surviving propagules. Spatially restricted recruitment appears to result mainly, if not exclusively, from the actions of host-restricted agents, principally microarthropods and fungi, that attack hosts in a distance-dependent fashion as Janzen and Connell proposed. Near total failure of propagules close to reproductive conspecifics ensures that successful reproduction occurs through a scant rain of dispersed seeds. Densities of dispersed seeds and seedlings arising from them are so low as to generally preclude the operation of density dependence, at least during early ontogenetic stages. I conclude that Janzen and Connell were essentially correct and that diversity maintenance results from top-down forcing acting in a spatially nonuniform fashion. PMID- 22322220 TI - Are dormant plants hedging their bets? Demographic consequences of prolonged dormancy in variable environments. AB - During the growing season, some individuals in perennial plant populations may remain alive belowground while others emerge. This phenomenon, known as prolonged dormancy, seems maladaptive, because prolonged dormancy delays growth and reproduction. However, prolonged dormancy may offer the benefit of safety while belowground, leading to the hypothesis that prolonged dormancy is a bet-hedging strategy. We evaluated this hypothesis using a 25-year demographic study of Astragalus scaphoides, an iteroparous perennial plant. First, we determined the relationship between prolonged dormancy and fitness using data from individuals in our population. This analysis showed that prolonged dormancy decreased arithmetic mean fitness and reduced variance in fitness. Geometric mean fitness was maximized at intermediate levels of prolonged dormancy. Empirical patterns of lifetime reproductive success confirm this relationship. We also compared fitness of plants in our population to hypothetical plants without prolonged dormancy, which generally revealed benefits of prolonged dormancy, even if plants could forgo prolonged dormancy without costs to other vital rates. Therefore, prolonged dormancy may indeed function as a bet-hedging strategy, but the benefits of remaining belowground outweigh the costs only for a subset of individuals. Bet hedging has been demonstrated in plants with simple life histories, such as annuals and monocarpic perennials; we present evidence that bet hedging may be important for plants with more complex life histories. PMID- 22322221 TI - Ecological specialization in fossil mammals explains Cope's rule. AB - Cope's rule is the trend toward increasing body size in a lineage over geological time. The rule has been explained either as passive diffusion away from a small initial body size or as an active trend upheld by the ecological and evolutionary advantages that large body size confers. An explicit and phylogenetically informed analysis of body size evolution in Cenozoic mammals shows that body size increases significantly in most inclusive clades. This increase occurs through temporal substitution of incumbent species by larger-sized close relatives within the clades. These late-appearing species have smaller spatial and temporal ranges and are rarer than the incumbents they replace, traits that are typical of ecological specialists. Cope's rule, accordingly, appears to derive mainly from increasing ecological specialization and clade-level niche expansion rather than from active selection for larger size. However, overlain on a net trend toward average size increase, significant pulses in origination of large-sized species are concentrated in periods of global cooling. These pulses plausibly record direct selection for larger body size according to Bergmann's rule, which thus appears to be independent of but concomitant with Cope's. PMID- 22322222 TI - The starvation-predation trade-off predicts trends in body size, muscularity, and adiposity between and within Taxa. AB - The storage of lipids to buffer energy shortage may incur such costs as increased vulnerability to predation, and animals may be more muscular in order to reduce such costs. If muscle and lipid mass interact to determine survival, then both the muscularity and the adiposity of animals will be affected by factors such as predator density and food availability. Here we explore how adiposity and muscularity may depend on such factors. We confirm the expectation that adiposity should decrease with the risk of predation and increase with the frequency of interruptions to the food supply. More surprisingly, the predicted relationships between skeletal size, muscularity, and adiposity qualitatively depended on various factors: for example, adiposity should increase with foraging costs only for small animals and should decrease with total body mass if competition for food is intense. Furthermore, if the locomotive costs of carrying lipids are low, then adiposity should increase with body mass, whereas if such costs are high, then adiposity should decrease with body mass. These predictions are supported by observations of variation between and within species. Our approach demonstrates that broad patterns of body composition can be understood in terms of the fundamental ecological trade-off between starvation and predation. PMID- 22322223 TI - Insects on plants: explaining the paradox of low diversity within specialist herbivore guilds. AB - Classical niche theory explains the coexistence of species through their exploitation of different resources. Assemblages of herbivores coexisting on a particular plant species are thus expected to be dominated by species from host specific guilds with narrow, coexistence-facilitating niches rather than by species from generalist guilds. Exactly the opposite pattern is observed for folivores feeding on trees in New Guinea. The least specialized mobile chewers were the most species rich, followed by the moderately specialized semiconcealed and exposed chewers. The highly specialized miners and mesophyll suckers were the least species-rich guilds. The Poisson distribution of herbivore species richness among plant species in specialized guilds and the absence of a negative correlation between species richness in different guilds on the same plant species suggest that these guilds are not saturated with species. We show that herbivore assemblages are enriched with generalists because these are more completely sampled from regional species pools. Herbivore diversity increases as a power function of plant diversity, and the rate of increase is inversely related to host specificity. The relative species diversity among guilds is thus scale dependent, as the importance of specialized guilds increases with plant diversity. Specialized insect guilds may therefore comprise a larger component of overall diversity in the tropics (where they are also poorly known taxonomically) than in the temperate zone, which has lower plant diversity. PMID- 22322224 TI - Tritrophic interactions at a community level: effects of host plant species quality on bird predation of caterpillars. AB - Effects of plant traits on herbivore-carnivore interactions are well documented in component communities but are not well understood at the level of large, complex communities. We report on a 2-year field experiment testing mechanisms by which variation in food quality among eight temperate forest tree species alters avian suppression of an assemblage of dietary generalist caterpillars. Plant quality and bird effects varied dramatically among tree species; high-quality plants yielded herbivores of 50% greater mass than those on low-quality plants, and bird effects ranged from near 0% to 97% reductions in caterpillar density. We also find evidence for two mechanisms linking host plant quality to bird effects. If caterpillar density was statistically controlled for, birds had relatively strong effects on the herbivores of low-quality plants, as predicted by the slow growth/high-mortality hypothesis. At the same time, caterpillar density increased with plant quality, and bird effects were density dependent. Consequently, the net effect of birds was strongest on the herbivores of high-quality plants, a dynamic we call the high-performance/high-mortality hypothesis. Host plant quality thus changes highly generalized herbivore-carnivore interactions by two complementary but opposing mechanisms. These results highlight the interrelatedness of plant-herbivore and herbivore-carnivore interactions and thus the importance of a tritrophic perspective. PMID- 22322225 TI - Covariation in life-history traits: differential effects of diet on condition, hormones, behavior, and reproduction in genetic finch morphs. AB - The relative contribution of genetic and environmental factors in determining variation in life-history traits is of central interest to evolutionary biologists, but the physiological mechanisms underlying these traits are still poorly understood. Here we experimentally demonstrate opposing effects of nutritional stress on immune function, endocrine physiology, parental care, and reproduction between red and black head-color morphs of the Gouldian finch (Erythrura gouldiae). Although the body condition of black morphs was largely unaffected by diet manipulation, red birds were highly sensitive to dietary changes, exhibiting considerable within-individual changes in condition and immune function. Consequently, nutritionally stressed red birds delayed breeding, produced smaller broods, and reared fewer and lower-quality foster offspring than black morphs. Differences in offspring quality were largely due to morph-specific differences in parental effort: red morphs reduced parental provisioning, whereas black morphs adaptively elevated their provisioning effort to meet the increased nutritional demands of their foster brood. Nutritionally stressed genetic morphs also exhibited divergent glucocorticoid responses. Black morphs showed reduced corticosterone-binding globulin (CBG) concentrations and increased levels of free corticosterone, whereas red morphs exhibited reduced free corticosterone levels and elevated CBG concentrations. These opposing glucocorticoid responses highlight intrinsic differences in endocrine sensitivities and plasticity between genetic morphs, which may underlie the morph-specific differences in condition, behavior, and reproduction and thus ultimately contribute to the evolution and maintenance of color polymorphism. PMID- 22322226 TI - Neural networks as mechanisms to regulate division of labor. AB - In social insects, workers perform a multitude of tasks, such as foraging, nest construction, and brood rearing, without central control of how work is allocated among individuals. It has been suggested that workers choose a task by responding to stimuli gathered from the environment. Response-threshold models assume that individuals in a colony vary in the stimulus intensity (response threshold) at which they begin to perform the corresponding task. Here we highlight the limitations of these models with respect to colony performance in task allocation. First, we show with analysis and quantitative simulations that the deterministic response-threshold model constrains the workers' behavioral flexibility under some stimulus conditions. Next, we show that the probabilistic response-threshold model fails to explain precise colony responses to varying stimuli. Both of these limitations would be detrimental to colony performance when dynamic and precise task allocation is needed. To address these problems, we propose extensions of the response-threshold model by adding variables that weigh stimuli. We test the extended response-threshold model in a foraging scenario and show in simulations that it results in an efficient task allocation. Finally, we show that response-threshold models can be formulated as artificial neural networks, which consequently provide a comprehensive framework for modeling task allocation in social insects. PMID- 22322227 TI - Allee effects may slow the spread of parasites in a coastal marine ecosystem. AB - Allee effects are thought to mediate the dynamics of population colonization, particularly for invasive species. However, Allee effects acting on parasites have rarely been considered in the analogous process of infectious disease establishment and spread. We studied the colonization of uninfected wild juvenile Pacific salmon populations by ectoparasitic salmon lice (Lepeophtheirus salmonis) over a 4-year period. In a data set of 68,376 fish, we observed 85 occurrences of precopular pair formation among 1,259 preadult female and 613 adult male lice. The probability of pair formation was dependent on the local abundance of lice, but this mate limitation is likely offset somewhat by mate-searching dispersal of males among host fish. A mathematical model of macroparasite population dynamics that incorporates the empirical results suggests a high likelihood of a demographic Allee effect, which can cause the colonizing parasite populations to die out. These results may provide the first empirical evidence for Allee effects in a macroparasite. Furthermore, the data give a rare detailed view of Allee effects in colonization dynamics and suggest that Allee effects may dampen the spread of parasites in a coastal marine ecosystem. PMID- 22322228 TI - Interacting impacts of invasive plants and invasive toads on native lizards. AB - The ecological impacts of an invasive species may be reduced by prior invasions if selective pressures imposed by earlier events preadapt the native biota to deal with the newer arrival. In northwestern Australia, invasion of the cane toad (Rhinella marina) kills many native predators if they ingest the highly toxic toads. Remarkably, the toads' defensive toxins (bufadienolides) are chemically similar to those of another invasive species: an ornamental plant from Madagascar, Bryophyllum spp. (Crassulaceae, mother-of-millions). Omnivorous lizards (bluetongue skinks, Tiliqua scincoides) are imperiled by the invasion of toads in northwestern Australia, but conspecifics from other areas of the continent (those where exotic plants were introduced and including areas where toads have yet to invade) are less affected because they exhibit higher physiological tolerance of toad toxins (and also of plant toxins). The willingness of captive bluetongues to consume both toads and these plants and the high correlation in the lizards' sensitivity to toad toxins versus plant toxins suggest that exotic plants may have imposed strong selection on the lizards' physiological tolerance of bufadienolides. As a result, populations of lizards from areas previously exposed to these alien plants may be preadapted to deal with the toxins of the more recent anuran invader. PMID- 22322229 TI - Pathogen persistence in the environment and insect-baculovirus interactions: disease-density thresholds, epidemic burnout, and insect outbreaks. AB - Classical epidemic theory focuses on directly transmitted pathogens, but many pathogens are instead transmitted when hosts encounter infectious particles. Theory has shown that for such diseases pathogen persistence time in the environment can strongly affect disease dynamics, but estimates of persistence time, and consequently tests of the theory, are extremely rare. We consider the consequences of persistence time for the dynamics of the gypsy moth baculovirus, a pathogen transmitted when larvae consume foliage contaminated with particles released from infectious cadavers. Using field-transmission experiments, we are able to estimate persistence time under natural conditions, and inserting our estimates into a standard epidemic model suggests that epidemics are often terminated by a combination of pupation and burnout rather than by burnout alone, as predicted by theory. Extending our models to allow for multiple generations, and including environmental transmission over the winter, suggests that the virus may survive over the long term even in the absence of complex persistence mechanisms, such as environmental reservoirs or covert infections. Our work suggests that estimates of persistence times can lead to a deeper understanding of environmentally transmitted pathogens and illustrates the usefulness of experiments that are closely tied to mathematical models. PMID- 22322230 TI - A predictive model of treatment outcome in patients with chronic HCV infection using IL28B and PD-1 genotyping. AB - BACKGROUND & AIMS: The advent of new chronic hepatitis C virus (HCV) therapies requires characterization of patients in order to predict adequate treatment. A good candidate marker is Programmed Cell Death-1 (PD-1) which is involved in progression of HCV infection. The aim of this study was to analyse the effect of several single nucleotide polymorphisms of PD-1 gene and several previously associated factors (IL28B and KIR receptors) on treatment responses. METHODS: 407 HCV chronic infected patients treated with PEG-IFN-alpha and ribavirin were recruited and classified according to their response to treatment. They were genotyped for PD-1 and IL28B polymorphisms, killer immunoglobulin-like receptors (KIR) and HLA genes. A multivariate logistic regression analysis and a Chi squared Automatic Interaction Detector (CHAID) prediction model of response included these and other clinical parameters. RESULTS: Our results showed that PD 1.3/A allele was significantly associated with sustained virological response (SVR) in a multivariate logistic regression analysis (p<0.01, OR=2.57). Additionally, IL28B C/C genotype was the most significant predictor of an SVR to treatment in all HCV genotypes (74.5%). In IL28B C/C patients, the presence of PD 1.3/A allele increased the probability of an SVR to 93.3%. Moreover, when this analysis was made only with patients infected by HCV-1, the predictive value of IL28B C/C genotype with PD-1.3/A allele was 90%. CONCLUSIONS: PD-1.3/A allele is associated with SVR to treatment and notably increases the predictive value of IL28B C/C genotype. Both markers in conjunction could be a useful tool, more relevant than HCV genotype in some cases, in clinical practice. PMID- 22322232 TI - Mechanistic biomarkers in acute liver injury: are we there yet? PMID- 22322233 TI - A silent partner no longer - sinusoidal endothelial cells in liver homeostasis and disease. PMID- 22322234 TI - Combination therapy for hepatocellular carcinoma: additive preclinical efficacy of the HDAC inhibitor panobinostat with sorafenib. AB - BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a heterogeneous cancer in which sorafenib is the only approved systemic therapy. Histone deacetylases (HDAC) are commonly dysregulated in cancer and therefore represent promising targets for therapies, however their role in HCC pathogenesis is still unknown. We analyzed the expression of 11 HDACs in human HCCs and assessed the efficacy of the pan-HDAC inhibitor panobinostat alone and in combination with sorafenib in preclinical models of liver cancer. METHODS: Gene expression and copy number changes were analyzed in a cohort of 334 human HCCs, while the effects of panobinostat and sorafenib were evaluated in three liver cancer cell lines and a murine xenograft model. RESULTS: Aberrant HDAC expression was identified and validated in 91 and 243 HCCs, respectively. Upregulation of HDAC3 and HDAC5 mRNAs was significantly correlated with DNA copy number gains. Inhibiting HDACs with panobinostat led to strong anti-tumoral effects in vitro and vivo, enhanced by the addition of sorafenib. Cell viability and proliferation declined, while apoptosis and autophagy increased. Panobinostat increased histone H3 and HSP90 acetylation, downregulated BIRC5 (survivin) and upregulated CDH1. Combination therapy with panobinostat and sorafenib significantly decreased vessel density, and most significantly decreased tumor volume and increased survival in HCC xenografts. CONCLUSIONS: Aberrant expression of several HDACs and copy number gains of HDAC3 and HDAC5 occur in HCC. Treatment with panobinostat combined with sorafenib demonstrated the highest preclinical efficacy in HCC models, providing the rationale for clinical studies with this novel combination. PMID- 22322235 TI - Neonatal iron overload and tissue siderosis due to gestational alloimmune liver disease. AB - BACKGROUND & AIMS: Gestational alloimmune liver disease is the main cause of the neonatal hemochromatosis phenotype, wherein severe neonatal liver disease is associated with iron overload and extrahepatic tissue siderosis. How fetal liver disease produces extrahepatic siderosis is not known. We hypothesized that fetal liver injury causes deficient hepcidin production and poor regulation of placental iron flux. Under the resulting conditions of iron overload, the tissue pattern of extrahepatic siderosis is determined by the normal expression of proteins involved in the import of non-transferrin-bound iron and the export of cellular iron. METHODS: Liver and extrahepatic tissues from infants with gestational alloimmune liver disease were examined and compared to normal age appropriate tissues. RESULTS: Serum iron indices indicate iron overload and excess non-transferrin bound iron in gestational alloimmune liver disease. The diseased liver showed significantly reduced hepcidin, hemojuvulin, and transferrin gene expression compared to the normal fetal and neonatal liver. Those extrahepatic tissues that are typically involved in pathological siderosis in neonatal hemochromatosis, whether from normal or diseased newborns, consistently expressed solute carrier family 39 (zinc transporter), member 14 (ZIP14) for non-transferrin-bound iron uptake and expressed little ferroportin for iron export. CONCLUSIONS: Excess non-transferrin-bound iron in gestational alloimmune liver disease may result from fetal liver injury that causes reduced synthesis of key iron regulatory and transport proteins. Whereas, the pattern of extrahepatic siderosis appears to be determined by the normal capacity of various tissues to import non-transferrin-bound iron and not export cellular iron. PMID- 22322236 TI - Role of the routine use of chest computed tomography and bone scan in staging workup of hepatocellular carcinoma. AB - BACKGROUND & AIMS: The value of chest computed tomography (CT) and bone scan (BS) during initial staging workup for hepatocellular carcinoma (HCC) patients has not been evaluated in a large patient group. METHODS: A prospective cohort of 381 patients who were initially diagnosed as having HCC at our institution between 2008 and 2010 was enrolled. We evaluated whether chest CT and BS could affect Barcelona Clinic Liver Cancer (BCLC) and Union for International Cancer Control (UICC) (7th) staging, compared with liver dynamic CT (LDCT) and chest X-ray. RESULTS: Abnormal findings on chest CT and BS were observed in 59.6% and 52.8% of 381 patients, respectively. Thirty and eight patients, respectively, had truly metastatic intrathoracic and bone lesions, with 19 (49.8%) and 7 (87.5%) exhibiting the same lesions on LDCT or chest X-ray. Of the 381 patients, 60 (15.7%), 134 (35.2%), 61 (16.0%), 119 (31.2%), and 7 (1.8%) had BCLC stages 0, A, B, C, and D, respectively; 176 (46.2%), 83 (21.8%), 41 (10.8%), 39 (10.2%), 0 (0%), 8 (2.1%), and 34 (8.9%) had UICC stages I, II, IIIA, IIIB, IIIC, IVA, and IVB, respectively before chest CT and BS. Only three of 381 patients showed a shift in BCLC stage [B->C (3/61, 4.9%)]. Chest CT and BS revealed additional metastases in only 1.1%, 14.0%, and 5.6% of patients with UICC stage T2, T3a, and T3b, respectively. CONCLUSIONS: Chest CT and BS do not provide additional information on metastasis in HCC patients with BCLC 0, A, C, or D stages, and UICC T1 or T4 stages on LDCT. PMID- 22322237 TI - Noradrenaline vs. terlipressin in the treatment of hepatorenal syndrome: a randomized study. AB - BACKGROUND & AIMS: Various vasoconstrictors are useful in the management of hepatorenal syndrome (HRS). Terlipressin is the drug of choice; however, it is expensive. In this study, we evaluated safety and efficacy of terlipressin and noradrenaline in the treatment of HRS. METHODS: Forty-six patients with HRS type 1 were managed with terlipressin (group A, N=23) or noradrenaline (Group B, N=23) with albumin in a randomized controlled trial at a tertiary center. RESULTS: HRS reversal could be achieved in 9 (39.1%) patients in group A and 10 (43.4%) patients in group B (p=0.764). Univariate analysis showed baseline Child Turcotte Pugh score (CTP), model of end stage liver disease (MELD), urine output on day 1(D1), albumin, and mean arterial pressure (MAP) were associated with response. However, on multivariate analysis only CTP score was associated with response. Fourteen patients in group A and 12 in group B died at day 15 (p>0.05). Noradrenaline was less expensive than terlipressin (p<0.05). No major adverse effects were seen. CONCLUSIONS: The results of this randomized study suggest that noradrenaline is as safe and effective as terlipressin, but less expensive in the treatment of HRS and baseline CTP score is predictive of response. PMID- 22322239 TI - Porous copper zinc tin sulfide thin film as photocathode for double junction photoelectrochemical solar cells. AB - Porous copper zinc tin sulfide (CZTS) thin film was prepared via a solvothermal approach. Compared with conventional dye-sensitized solar cells (DSSCs), double junction photoelectrochemical cells using dye-sensitized n-type TiO(2) (DS TiO(2)) as the photoanode and porous p-type CZTS film as the photocathode shows an increased short circuit current, external quantum efficiency and power conversion efficiency. PMID- 22322240 TI - Characteristic CYP2A6 genetic polymorphisms detected by TA cloning-based sequencing in Chinese digestive system cancer patients with S-1 based chemotherapy. AB - S-1 is an oral antitumor agent that contains tegafur, which is converted to fluorouracil (5-FU) in the human body. Cytochrome P450 2A6 (CYP2A6) is the principal enzyme responsible for bioconversion of tegafur to 5-FU. A number of CYP2A6 polymorphisms have been associated with variations in enzyme activity in several ethnic populations. The CYP2A6*4C allele leads to deletion of the entire CYP2A6 gene, and is the main finding in patients with reduced CYP2A6 enzymatic activity. Thus, the aim of our study was to evaluate the allele frequencies of CYP2A6 polymorphisms in a population with cancer of the digestive system. We developed a simple screening method, which combined TA cloning and direct sequencing, to detect CYP2A6 genetic polymorphisms in Chinese patients with cancers of the digestive system. A total of 77 patients with various types of digestive system cancers were screened for CYP2A6 genetic polymorphisms. The allele frequencies of CYP2A6*1A, CYP2A6*1B and CYP2A6*4C in the 77 patients screened were 62, 42 and 13%, respectively. Frequencies of the homozygous genotypes for CYP2A6*1A and CYP2A6*4C were 27 and 12%, respectively. As expected, patients that were determined to be homozygous for CYP2A6*4C exhibited the characteristic chemotherapy efficacy and toxicity profiles. The TA cloning-based direct sequencing method facilitated allele frequency and genotyping determination for CYP2A6*1A, 1B and 4C of cancer patients. The findings indicated that the population carries a high frequency of the CYP2A6*4C homozygous genotype. Thus, the reduced efficacy of standard chemotherapy dosage in Chinese cancer patients may be explained by the lack of CYP2A6-mediated S-1 bioconversion to 5-FU. PMID- 22322241 TI - PRKCB is associated with calcineurin inhibitor-induced renal dysfunction in heart transplant recipients. AB - OBJECTIVES: Single nucleotide polymorphisms (SNPs) in the transforming growth factor-beta1 gene (TGFB1) have been inconsistently associated with calcineurin inhibitor (CNI)-induced renal dysfunction following cardiac transplantation. The impact of genetic variants related to the renin-angiotensin-aldosterone system (RAAS) and natriuretic peptides, which are implicated in CNI nephrotoxicity, is unknown. The primary objective of this study was to validate the association between two common variants in TGFB1 (rs1800470, rs1800471) and postcardiac transplant renal function. The secondary objective was to investigate the effect of candidate genes related to the RAAS, natriuretic peptides, and other elements involved in the intracellular signaling of these pathways. METHODS: We conducted a retrospective cohort study of 158 heart transplant recipients treated with CNIs, and evaluated the association between select SNPs and the estimated glomerular filtration rate as calculated by the Modification of Diet in Renal Disease simplified formula. A total of 273 SNPs distributed in 44 genes were tested. RESULTS: No association was observed between TGFB1 variants and renal function. One polymorphism in the protein kinase C-beta gene (PRKCB; rs11074606), which is implicated in the RAAS intracellular signaling, was significantly associated with post-transplant estimated glomerular filtration rate after adjusting for possible confounders (P=0.00049). This marker is in linkage disequilibrium with two variants located in putative regulatory regions of the gene (rs2283541, rs1013316). CONCLUSION: Our results suggest that PRKCB may be a potential predictor of CNI-induced nephrotoxicity in heart transplant recipients, and could therefore be a promising candidate to identify patients who are most susceptible to this adverse drug reaction. PMID- 22322242 TI - Merging pharmacometabolomics with pharmacogenomics using '1000 Genomes' single nucleotide polymorphism imputation: selective serotonin reuptake inhibitor response pharmacogenomics. AB - OBJECTIVE: We set out to test the hypothesis that pharmacometabolomic data could be efficiently merged with pharmacogenomic data by single-nucleotide polymorphism (SNP) imputation of metabolomic-derived pathway data on a 'scaffolding' of genome wide association (GWAS) SNP data to broaden and accelerate 'pharmacometabolomics informed pharmacogenomic' studies by eliminating the need for initial genotyping and by making broader SNP association testing possible. METHODS: We previously genotyped 131 tag SNPs for six genes encoding enzymes in the glycine synthesis and degradation pathway using DNA from 529 depressed patients treated with citalopram/escitalopram to pursue a glycine metabolomics 'signal' associated with selective serotonine reuptake inhibitor response. We identified a significant SNP in the glycine dehydrogenase gene. Subsequently, GWAS SNP data were generated for the same patients. In this study, we compared SNP imputation within 200 kb of these same six genes with the results of the previous tag SNP strategy as a rapid strategy for merging pharmacometabolomic and pharmacogenomic data. RESULTS: Imputed genotype data provided greater coverage and higher resolution than did tag SNP genotyping, with a higher average genotype concordance between genotyped and imputed SNP data for '1000 Genomes' (96.4%) than HapMap 2 (93.2%) imputation. Many low P-value SNPs with novel locations within genes were observed for imputed compared with tag SNPs, thus altering the focus for subsequent functional genomic studies. CONCLUSION: These results indicate that the use of GWAS data to impute SNPs for genes in pathways identified by other 'omics' approaches makes it possible to rapidly and cost efficiently identify SNP markers to 'broaden' and accelerate pharmacogenomic studies. PMID- 22322243 TI - Novel access to carbodiphosphoranes in the coordination sphere of group 10 metals: template synthesis and protonation of PCP pincer carbodiphosphorane complexes of C(dppm)2. AB - In a novel template synthesis of carbodiphosphoranes (CDPs), the phosphine functionalized CDP ligand C(dppm)(2) (dppm = Ph(2)PCH(2)PPh(2)) is formed in the coordination sphere of group 10 metals from CS(2) and 4 equivalents of dppm. The products are the PCP pincer complexes [M(Cl)(C(dppm)(2)-kappa3P,C,P)]Cl (M = Ni, Pd, Pt) and 2 equivalents of dppmS. The compound C(dppm)(2), which is composed of a divalent carbon atom and two dppm subunits, represents a new PCP-type pincer ligand with the formally neutral carbon Lewis base of the CDP functionality as the central carbon. Treatment of [M(Cl)(C(dppm)(2)-kappa3P,C,P)]Cl (M = Pd, Pt) with hydrochloric acid results in protonation at the CDP carbon atom and the formation of the PCP pincer complexes [M(Cl)(CH(dppm)(2)-kappa3P,C,P)]Cl(2) (M = Pd, Pt). The PCP pincer ligand [CH(dppm)(2)](+) involves a formally cationic central carbon donor. The reaction of [Ni(Cl)(C(dppm)(2)-kappa3P,C,P)]Cl with HCl leads to the extrusion of NiCl(2) and formation of the diprotonated CDP compound [CH(2)(dppm)(2)]Cl(2), from which the monoprotonated conjugate base [CH(dppm)(2)]Cl is obtained upon addition of bases, such as NH(3). The crystal structures of [M(Cl)(C(dppm)(2)-kappa3P,C,P)]Cl (M = Ni, Pd, Pt), [Ni(Cl)(C(dppm)(2)-kappa3P,C,P)](2)[NiCl(4)], [M(Cl)(CH(dppm)(2) kappa3P,C,P)]Cl(2) (M = Pd, Pt) as well as [CH(2)(dppm)(2)]Cl(2) and [CH(dppm)(2)]Cl are presented. A comparison of the solid state structures reveals interesting features, e.g. infinite supramolecular networks mediated by C-H...Cl hydrogen bond interactions and an unexpected loss of molecular symmetry upon protonation in the complexes [M(CH(dppm)(2)-kappa3P,C,P)(Cl)]Cl(2) (M = Pd, Pt) as a result of the flexible ligand backbone. Additionally the new compounds were characterized comprehensively in solution by multinuclear (31)P, (13)C and (1)H NMR spectroscopy: Several spectroscopic parameters show a striking variability in particular regarding the carbodiphosphorane functionality. Furthermore the compound [Ni(Cl)(C(dppm)(2)-kappa3P,C,P)]Cl was examined by cyclic voltammetry (CV) and could be shown to display quasi-reversible oxidative as well as reductive behaviour. PMID- 22322244 TI - Anomalous thickness-dependence of photocurrent explained for state-of-the-art planar nano-heterojunction organic solar cells. AB - Due to their simple geometry and design, planar heterojunction (PHJ) solar cells have advantages both as potential photovoltaics with more efficient charge extraction than their bulk heterojunction (BHJ) counterparts, and as idealized interfaces to study basic device operation. The main reason for creating BHJs was the limited exciton diffusion length in the active materials of the PHJ: if an exciton is generated at a distance greater than its diffusion length from the hetero-interface of the PHJ, it would be very unlikely to be able to contribute to the photocurrent. Based on this argument one expects a maximum in the photocurrent of PHJs for a thickness of the active layer equal to the exciton diffusion length (~10 nm). However, in two recently developed PHJs that have appeared in the literature, a maximum photocurrent is observed for 60-65 nm of poly(3-hexylthiophene) (P3HT). In this work, we explore this anomaly by combining both an optical T-matrix and a kinetic Monte Carlo simulation that tracks the exciton behavior in the PHJs. The two systems considered are a P3HT/single walled carbon nanotube (SWNT) device, and a P3HT/phenyl-C61-butyric acid methyl ester (PCBM) device. The model demonstrates how a bulk exciton sink can explain the shifted maximum in the P3HT/SWNT case, whereas in the P3HT/PCBM case the maximum is mainly determined by PCBM molecules interdiffusing in the P3HT upon annealing. Based upon the results of this model it will be possible to more intelligently design nanostructured photovoltaics and optimize them toward higher efficiencies. PMID- 22322245 TI - Polysaccharide isolated from Triticum aestivum stimulates insulin release from pancreatic cells via the ATP-sensitive K+ channel. AB - Traditional natural plants have been used throughout the world for their antidiabetic effects. The aim of the present study was to investigate the stimulating activity of a polysaccharide extract derived from T. aestivum sprout (TASP) on insulin secretion in vitro using the RIN-5F pancreatic beta-cell line and rat pancreatic islets. In these experiments, TASP (0.1 to 2 mg/ml) augmented glucose-stimulated insulin secretion in a dose-dependent manner in the presence of a stimulatory glucose concentration (16.7 mM), but not of a basal concentration (1.1 mM). Although TASP failed to enhance the high K+-induced insulin secretion, the insulinotropic effect of TASP was significantly inhibited by diazoxide, an opener of ATP-sensitive K+ channel blocking insulin release. TASP potentiated the insulin secretion induced by other secretagogues, such as IBMX and tolbutamide. Moreover, glucose-derived blood insulin levels were significantly elevated by oral administration of TASP to mice, similarly to antidiabetic drugs. We also demonstrated that TASP significantly increased glucose-induced 45Ca2+ uptake and proinsulin mRNA expression in rat islets. Overall, our results suggest that TASP has a stimulating effect on insulin secretion and production in pancreatic beta-cells via K+ channel closure and calcium influx. These results suggest that TASP may be useful as a candidate for the therapy of diabetes mellitus. PMID- 22322246 TI - Cardiovascular complications in patients with megaesophagus due to Chagas disease undergoing the Serra-Doria operation. AB - The Serra-Doria procedure has been used in the treatment of advanced or relapsed megaesophagus due to Chagas disease. Little is known, however, about cardiovascular complications following this procedure. The purpose of this study was to settle independent predictors of cardiovascular complications following the Serra-Doria procedure in patients with megaesophagus secondary to chronic Chagas disease. A total of 76 patients who underwent the Serra-Doria operation for Chagas disease megaesophagus from 1998 to 2010 were included. A multivariate stepwise logistic regression analysis was performed to identify predictors of cardiovascular complications. Mean age was 61+/-10 years; 55% were male. Advanced megaesophagus (grades III/IV) were found in 65 (86%) of patients. Twenty-two (29%) patients had one comorbidity, and five (7%) three co-morbidities before operation. Two (3%) patients died following the operation. Twenty-nine (38%) patients presented cardiovascular complication following the Serra-Doria procedure; 15 (44%) were mild, 7 (21%) moderate, and 12 (35%) severe. Age>61 years was the only independent predictor of cardiovascular complication following Serra-Doria procedure. In patients with megaesophagus secondary to chronic Chagas disease, the Serra-Doria procedure is associated with a low mortality rate and a high frequency of cardiac complication. PMID- 22322247 TI - Immunological properties of Hypnale hypnale (hump-nosed pit viper) venom: antibody production with diagnostic and therapeutic potentials. AB - Envenomation by hump-nosed pit viper (Hypnale hypnale, Hh) in Sri Lanka has caused significant morbidity and mortality, attributed to 35% of total venomous snakebites. In Southwestern India (Kerala), H. hypnale was increasingly identified as a dangerous and common source of envenomation, second to the Russell's viper but ahead of the cobra bites. Unfortunately, there is still no specific antivenom to date. This study aims to investigate the immunological properties of the venom and to assess the feasibility of specific Hh antivenom production as well as the development of a diagnostic assay. Hh venom elicited satisfactory titers of anti-Hh IgG in rabbits after 3rd immunization. The anti-Hh IgG, isolated with caprylic acid precipitation method, was effective in neutralizing the venom lethality (potency=48 LD(50) per ml IgG) as well as its procoagulant, hemorrhagic and necrotic effects, indicating the possibility to produce the specific antivenom using the common immunization regime. Cross reactivity studies using indirect ELISA showed that anti-Hh IgG cross-reacted extensively with several Asiatic crotalid venoms, particularly that of Calloselasma rhodostoma (73.6%), presumably due to the presence of venom antigens common to both snakes. Levels of immunological cross-reactivity were vastly reduced with double-sandwich ELISA. Further work demonstrated that the assay was able to distinguish and quantify venoms of H. hypnale, Daboia russelii and Echis carinatus sinhaleyus (three common local viperid) used to spike human sera at various concentrations. The assay hence may be a useful investigating tool for diagnosing biting species and studying the time course profile of venom concentrations in blood. PMID- 22322248 TI - The glycosidation of xenobiotics and endogenous compounds: versatility and redundancy in the UDP glycosyltransferase superfamily. AB - The covalent addition of sugars to small organic molecules is mediated by a superfamily of UDP glycosyltransferases (UGTs) found in animals, plants and bacteria. This superfamily evolved by gene duplication and divergence to manage exposure to a changing environment of lipophilic chemicals. The recent characterization of the UGT3A family provides further insights into the origin and evolution of this superfamily in mammals and the role of individual UGTs in the formation of the various chemical glycosides found in body tissues and fluids. Furthermore, the unique UDP-sugar specificities of the two enzymes in this family inform our knowledge of UGT structure relating to catalysis and UDP sugar specificity. In addition to the UGT3 gene family, three other gene families, UGTs1, 2, and 8, are found in mammalian genomes. The 19 members of the UGT1 and 2 families have a major role in processing lipophilic chemicals due to their capacity to glucuronidate a broad range of structurally-dissimilar substrates. In contrast, the UGT3 enzymes only have a minor role, as their activities are very low in the major drug-metabolic organs, and their N acetylglucosaminide and glucoside products are only a minor component of circulating and excreted drug metabolites. Although the endogenous role of the UGT3 family is still unknown, participation in the processing of lipophilic chemicals in specific cell types or at specific times during ontogeny cannot be excluded. In contrast to the UGT 1, 2 and 3 families, the single member of the UGT8 family appears to have no role in drug metabolism. PMID- 22322249 TI - Identification of a novel phosphatase with high affinity for nucleotides monophosphate from common bean (Phaseolus vulgaris). AB - Common bean (Phaseolus vulgaris) seedlings accumulate ureides derived from purines after germination. The first step in the conversion of purines to ureides is the removal of the 5'-phosphate group by a phosphatase that has not been established yet. Two main phosphatase activities were detected in the embryonic axes of common bean using inosine monophosphate as substrate in an in-gel assay. Both activities differed in their sensitive to the common phosphatase inhibitor molybdate, with the molybdate-resistant as the first enzyme induced after radicle protrusion. The molybdate-resistant phosphatase has been purified to electrophoretic homogeneity and this is the first enzyme which shows this resistance purified and characterized from plant tissues. The native enzyme was a monomer of 55 kDa and it showed highest activity with nucleotides as substrates, with the K(m) values in the micromolar range. Among nucleotides, the highest specific constant (V(max)/K(m)) was observed for adenosine monophosphate. Furthermore, the enzyme was inhibited by nucleosides, the products of the enzymatic reaction, with maximum effect for adenosine. Common bean seedlings imbibed in the presence of adenosine monophosphate in vivo showed the highest molybdate-resistant phosphatase activity in the axes in addition to increased ureide content. The data presented suggests that purified phosphatase is involved in nucleotide metabolism in embryonic axes from common bean. PMID- 22322250 TI - Comparative effect of 28 homobrassinolide and salicylic acid in the amelioration of NaCl stress in Brassica juncea L. AB - Among various environmental stresses, salt stress is extensively damaging to major crops all over the world. An experiment was conducted to explore the role of exogenously applied 28 homobrassinolide (HBL) and salicylic acid (SA) on growth, photosynthetic parameters, transpiration and proline content of Brassica juncea L. cultivar Varuna in presence or absence of saline conditions (4.2 dsm( 1)). The leaves of 29d old plants were sprayed with distilled water, HBL and/or SA and plant responses were studied at 30 days after sowing (24 h after spray) and 45 days after sowing. The salinity significantly reduced the plant growth, gas exchange parameters but increased proline content and electrolyte leakage in the leaves. The effects were more pronounced at 30 DAS than 45 DAS. Out of the two hormones (HBL/SA) HBL excelled in its effects at both sampling stages. Toxic effects generated by salinity stress were completely overcome by the combination of the two hormones (HBL and SA) at 45 DAS. PMID- 22322251 TI - Syndrome differentiation in modern research of traditional Chinese medicine. AB - Syndrome differentiation (Bian Zheng) in traditional Chinese medicine (TCM) is the comprehensive analysis of clinical information gained by the four main diagnostic TCM procedures: observation, listening, questioning, and pulse analysis, and it is used to guide the choice of treatment either by acupuncture and/or TCM herbal formulae, that is, Fufang. TCM syndrome differentiation can be used for further stratification of the patients' conditions with certain disease, identified by orthodox medical diagnosis, which could help the improvement of efficacy of the selected intervention. In modern TCM research it is possible to integrate syndrome differentiation with orthodox medical diagnosis leading to new scientific findings in overall medical diagnosis and treatment. In this review, the focus is to screen published evidence on the role of syndrome differentiation in modern TCM research with particular emphasis on basic and clinical research as well as, pharmacological evaluation of TCM herbal formulary for drug discovery. PMID- 22322252 TI - Antibacterial activity of crinane alkaloids from Boophone disticha (Amaryllidaceae). AB - ETHNOPHARMACOLOGICAL RELEVANCE: Boophone disticha (Amaryllidaceae) is one of the most common bulbous plants used for medicinal purposes by the indigenous people of southern Africa. Its use as a narcotic substance by the Khoi/San tribes has been known for several centuries, while the Sotho, Xhosa and Zulu people are known to use the plant to treat a host of ailments, including inflammation, wounds, gynaecological conditions and psychosis. AIM OF THE STUDY: Much of the pharmacological work on the plant, such as affinity to the serotonin transporter, has been based on its reputed usage for narcotic purposes. However, its widespread use to treat wounds and infections has not been linked to a specific chemical entity. In this regard, Boophone disticha was here examined for its phytochemical composition which could shed light on the use of the plant for such purposes. MATERIALS AND METHODS: The known crinane alkaloids buphanidrine and distichamine were isolated via column chromatography of the ethanolic extract of bulbs of Boophone disticha. Structural details of the compounds were determined by high field 2D NMR and mass spectroscopic techniques. Microbial activity against selected Gram-positive and Gram-negative bacteria was ascertained according to the micro-dilution assay. RESULTS: Both buphanidrine and distichamine were uncovered as novel, broad spectrum moderately active, antibacterial agents with the best MIC value detected at 0.063mg/ml for Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae. MIC values for Bacillus subtilis were two-fold less than that observed for the other three bacteria, suggesting that the extract and pure compounds were selective in their interaction with the bacterial pathogens. CONCLUSION: Phytochemical investigation of Boophone disticha has led to the identification of two known crinanes, buphanidrine and distichamine. Based on the reputed traditional use of the plant for wounds and infections, both compounds were screened for antibacterial activity which revealed them to be novel, broad spectrum antibacterial agents with the best MIC value set at 0.063mg/ml. Their close structural similarity may have bearing on their similar activity profiles. PMID- 22322253 TI - A review of Omics research in acupuncture: the relevance and future prospects for understanding the nature of meridians and acupoints. AB - RELEVANCE: Acupuncture is an intrinsic part of traditional Chinese medicine. The current understanding of the acupuncture meridian system, acupoints and the potential utilizing Omics technologies are summarized in this review. MATERIAL AND METHODS: A systematic search for acupuncture involving Omics technologies was carried out using multiple online literature databases. The records retrieved were from the full collections of each database dated to September 2011. Data produced from functional genomic technologies were extracted from the collected acupuncture/moxibustion studies and subjected to evaluation. Analyses and comments were summarized on the advances in experimental research in acupuncture/moxibustion-related studies, and the future for strategies and approaches in the era of functional genomics highlighted. RESULTS: An overview of articles indicated that several diseases or symptoms with evidence of effectiveness had been piloted for using functional genomic technologies, such as Parkinson's disease, allergic disorders, pain, and spinal cord injury, most of which are chronic "difficult diseases". High-throughput genomic and proteomic profiling of gene expression in tissues has been able to identify potential candidates for the effects of acupuncture and provide valuable information toward understanding the possible mechanisms of the therapy. However, without further holistic and sophisticated analyses in the context of metabolomics and systems biology, the current attempts and the foreseeable developments appear to be insufficient to produce firm conclusions. Noticeably, the recent rapid advances in functional molecular imaging targeting specific metabolites have shown great promise and if combined with other post-genomic technologies, could be extremely helpful for the acupuncture studies in human subjects. CONCLUSION: This review suggest that disease-oriented studies using the approach of multi-indexed high throughput technologies and systems biology analyses will be a preferred strategy for future acupuncture/moxibustion research. PMID- 22322255 TI - Reverse vaccinology on the cusp. PMID- 22322254 TI - Cancer biomarkers: selecting the right drug for the right patient. AB - This Perspective highlights biomarkers that are expressed as a consequence of cancer development and progression. We focus on those biomarkers that are most relevant for identifying patients who are likely to respond to a given therapy, as well as those biomarkers that are most effective for measuring patient response to therapy. These two measures are necessary for selecting the right drug for the right patient, regardless of whether the setting is in drug development or in the post-approval use of the drug for patients with cancer. We also discuss the innovative designs of clinical trials and methodologies that are used to validate and qualify biomarkers for use in specific contexts. Furthermore, we look ahead to the promises and challenges in the field of cancer biomarkers. PMID- 22322256 TI - Malignant middle cerebral artery infarction. AB - PURPOSE OF REVIEW: This review will report on the new aspects of management of 'malignant' middle cerebral artery (MCA) infarctions. RECENT FINDINGS: Large MCA infarctions have been associated with high death rates for years. The most reliable predictors of a 'malignant' course are hypodensity in more than 50% of the MCA territory on computed tomography as well as stroke volume greater than 145 ml on diffusion-weighted imaging. Real-time neuromonitoring may be helpful in the detection of development of cerebral edema. The attempt of recanalization of the affected artery utilizing a combination of intravenous and intra-arterial thrombolysis and mechanical thrombectomy is crucial. Monitoring of intracranial pressure has not been proven helpful. Decompressive surgery within 48 h after symptom onset in patients less than 60 years old reduces mortality and severe disability. The quality of life perceived by the survivors is variable and deserves further study. The neuroprotective effect of hypothermia requires additional investigation. SUMMARY: The era of decompressive hemicraniectomy has changed the prospects of patients with large infarctions in the MCA or internal carotid artery territory who are at risk of development of 'malignant' cerebral edema. Timing of surgery and appropriate patient selection based on age and other criteria need to be refined. PMID- 22322257 TI - Blood pressure control for acute ischemic and hemorrhagic stroke. AB - PURPOSE OF REVIEW: Acute stroke, including the subtypes of ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH), typically involves significant fluctuations in blood pressure (BP). Treatment of BP after all stroke types is controversial. In each case, there are theoretical dangers to leaving BP alone as well as altering it artificially. In this article, we review the role of BP in each stroke subtype and the existing evidence for BP optimization. RECENT FINDINGS: Except in patients receiving thrombolytic therapy, there is insufficient evidence to recommend active BP management in ischemic stroke. In ICH, the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) trial and Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT) have demonstrated that systolic BP reduction to 140 mmHg is well tolerated and associated with attenuation of hematoma expansion. The impact of BP reduction on outcomes is being evaluated in the ongoing phase III ATACH II and INTERACT 2 trials. No evidence exists to recommend definitive BP management strategies in acute SAH, although hypertension should likely be avoided before an aneurysm is secured, and hypotension should be avoided altogether. SUMMARY: Evidence for BP management in acute stroke is limited, although large randomized trials are currently in progress for both ischemic stroke and ICH. BP management in SAH remains woefully understudied. PMID- 22322258 TI - Manifestations of the hyperadrenergic state after acute brain injury. AB - PURPOSE OF REVIEW: Hyperadrenergic activity leading to autonomic dysfunction after acute brain injury is an underrecognized, yet important source of complications following a variety of neurologic injuries. Autonomic dysfunction may prolong ICU stay and increase healthcare costs driven by extensive diagnostic workups and/or ensuing complications. In this review article, we intend to illustrate commonalities between various hyperadrenergic states in acquired brain injury. Specifically, this review will focus on autonomic dysfunction in two common conditions in the neurocritical care unit, traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH). RECENT FINDINGS: Elevated levels of catecholamines have been well documented in SAH and to a lesser extent in paroxysmal sympathetic hyperactivity, hinting at the underlying increased sympathetic tone in both disease states. The resultant hyperadrenergic state may manifest with vital sign alterations, or end-organ dysfunction such as heart failure. Neuroimaging and limited clinical data have elucidated some information regarding underlying mechanisms, but the gaps in understanding have thus far limited prospective clinical trials. A multitude of therapeutic options to reduce adrenergic tone have been employed with varying degrees of success. SUMMARY: The pathophysiology of autonomic dysfunction is incompletely understood and treatment options are few. However, recognizing hyperadrenergic commonality in disparate neurologic disease may facilitate novel inquiries into lesion localization and therapeutics. It is possible that adrenergic blockade may diminish or abrogate end-organ dysfunction in TBI and SAH. PMID- 22322259 TI - Brain multimodality monitoring: an update. AB - PURPOSE OF REVIEW: An important goal of neurocritical care is the management of secondary brain injury (SBI), that is pathological events occurring after primary insult that add further burden to outcome. Brain oedema, cerebral ischemia, energy dysfunction, seizures and systemic insults are the main components of SBI. We here review recent data showing the clinical utility of brain multimodality monitoring (BMM) for the management of SBI. RECENT FINDINGS: Despite being recommended by international guidelines, standard intracranial pressure (ICP) monitoring may be insufficient to detect all episodes of SBI. ICP monitoring, combined with brain oxygen (PbtO(2)), cerebral microdialysis and regional cerebral blood flow, might help to target therapy (e.g. management of cerebral perfusion pressure, blood transfusion, glucose control) to patient-specific pathophysiology. Physiological parameters derived from BMM, including PbtO(2) and microdialysis lactate/pyruvate ratio, correlate with outcome and have recently been incorporated into neurocritical care guidelines. Advanced intracranial devices can be complemented by quantitative electroencephalography to monitor changes of brain function and nonconvulsive seizures. SUMMARY: BMM offers an on line comprehensive scrutiny of the injured brain and is increasingly used for the management of SBI. Integration of monitored data using new informatics tools may help optimize therapy of brain-injured patients and quality of care. PMID- 22322260 TI - ICU delirium: an update. AB - PURPOSE OF REVIEW: Delirium is frequently encountered in the ICU and is associated with significant adverse outcomes. The increasingly recognized consequences of ICU delirium should enhance efforts to improve recognition and management of this serious problem. We aim to review the recent literature on ICU delirium, including risk factors, detection, management and long-term impact of disease. RECENT FINDINGS: We present the most recent evidence on risk factors for ICU delirium and its persistence. In addition, we aim to clarify some of the confusion surrounding the tools for detection and their limitation in practice. The literature reflects long-term neurocognitive impairments following ICU delirium and supports efforts to reduce these negative outcomes using protocol driven sedation and ventilator management. Although haloperidol is widely accepted as the preferred pharmacologic treatment for delirium, its use is not seeded in robust evidence. Limited studies reflect the safety of atypical antipsychotics for treatment but lack clear improvement in delirium-related outcomes. We place an emphasis on the use of protocols to reduce the use of sedatives, particularly benzodiazepines in the management of ICU delirium. SUMMARY: Delirium remains an underrecognized and underdiagnosed problem. Detection tools are readily available and easy to use. Further understanding of risk factors is needed to identify most susceptible individuals and plan management, which should include prevention and therapy based on available evidence. PMID- 22322261 TI - Refractory status epilepticus. AB - PURPOSE OF REVIEW: Refractory status epilepticus (RSE) has a high morbidity and mortality. There are currently no definitive data to guide both the optimal choice of therapy and treatment goals. This review focuses on RSE diagnosis and outcome and discusses both commonly used and anecdotal therapies for RSE. RECENT FINDINGS: The challenges in performing randomized controlled trials (RCTs) in neurocritical care and more specifically for the treatment of RSE are illustrated by the early termination of the first RCT of RSE due to low recruitment that compared propofol to barbiturates. Recent case series include the successful treatment of recurrent RSE with ketamine, intravenous lacosamide as an add-on treatment, the use of combination antiepileptics (phenytoin, levetiracetam, and pregabalin), and surgical treatments (vagal nerve and deep brain stimulation) for the control of RSE. SUMMARY: A number of different therapeutic options are available for the treatment of RSE but none have been shown to be superior to others at this point. PMID- 22322262 TI - Ghrelin, appetite and critical illness. AB - PURPOSE OF REVIEW: Recovery and rehabilitation after critical illness is a vital part of intensive care management. The role of feeding and nutritional intervention is the subject of many recent studies. The gastric hormone ghrelin has effects on appetite and food intake and on immunomodulatory functions. Here we review the interactions between critical illness, appetite regulation, nutrition and ghrelin. RECENT FINDINGS: Critical illness results in significant loss of lean body mass; strategies to prevent this have so far proven unsuccessful. Ghrelin has been shown to reduce catabolic protein loss in animal models of critical illness and improve body composition in chronic cachectic illnesses in humans. SUMMARY: Enhancing recovery from critical illness will improve both short-term and long-term outcomes. Ghrelin may offer an important means of improving appetite, muscle mass and rehabilitation in the period after critical illness, although studies are needed to see whether this potential is realized. PMID- 22322263 TI - Nutrition therapy in the critically ill child. AB - PURPOSE OF REVIEW: Malnutrition and obesity are prevalent in children admitted to the pediatric intensive care unit. Nutritional deterioration secondary to suboptimal nutrient delivery can adversely affect outcomes during pediatric critical illness. This review highlights the recent investigations of nutrition assessment, energy balance, indirect calorimetry, nutrition therapy, barriers to nutrient delivery, monitoring during enteral feeding, and the role of nutrition guidelines in critically ill children. RECENT FINDINGS: Critically ill children are at high risk for energy and protein imbalance. Indirect calorimetry remains the only accurate method to assess energy requirements in this population. Intensive insulin therapy to achieve glycemic control may reduce morbidity and mortality in adults, but risks hypoglycemia in critically ill children. Early enteral nutrition improves nutrition outcomes and adherence to nutrition guidelines can overcome barriers to optimal nutrition therapy. SUMMARY: Timely and adequate nutrition therapy is essential to improve nutrition outcomes in critically ill children. Further research is required to determine clinical outcome benefits with indirect calorimetry and enteral nutrition guidelines, and to identify optimal glucose targets. PMID- 22322264 TI - Determining energy needs in critically ill patients: equations or indirect calorimeters. AB - PURPOSE OF REVIEW: The review focuses on current methodology for the most accurate way to determine resting metabolic rate in critically ill patients and to evaluate whether application of any particular method improves clinical outcome. RECENT FINDINGS: Consensus is that indirect calorimetry is the most accurate method for determining resting metabolic rate. Whenever an alternate method of determining energy expenditure is tested (e.g. equations), the criterion method used in the validation is indirect calorimetry. Of the alternates to indirect calorimetry, the Penn State equation has the strongest validation work supporting it. No study has been undertaken to determine whether the drop in accuracy associated with estimation methods translates into deterioration in clinical outcome compared to nutrition support guided by measurements. SUMMARY: Indirect calorimetry is the most accurate way to determine calorie needs in critically ill patients. Compared to indirect calorimetry, metabolic rate equations are accurate about 75% of the time. No study has been performed to determine whether the measurement or estimation method improves clinical outcome. PMID- 22322266 TI - A new approach to defining and diagnosing malnutrition in adult critical illness. AB - PURPOSE OF REVIEW: This review will highlight a new approach to defining malnutrition syndromes for critically ill adults that incorporates a modern understanding of the contributions of inflammatory response. A systematic approach to nutrition assessment is described to help support diagnosis. RECENT FINDINGS: Recent findings suggest that varying degrees of acute or chronic inflammation are key contributing factors in the pathogenesis of malnutrition in the setting of disease or injury. Newly proposed malnutrition syndromes include: 'starvation-associated malnutrition', when there is chronic starvation without inflammation; 'chronic disease-associated malnutrition', when inflammation is chronic and of mild to moderate degree; and 'acute disease or injury-associated malnutrition', when inflammation is acute and of severe degree. SUMMARY: Inflammation and malnutrition have an intimate interplay; the presence of inflammation contributes to the development of malnutrition and often limits the effectiveness of nutritional interventions. In turn, the associated malnutrition may blunt the effectiveness of medical therapies. A new approach to defining and diagnosing malnutrition syndromes can help to guide intervention and expected outcomes. PMID- 22322265 TI - Hypoxia signaling during intestinal ischemia and inflammation. AB - PURPOSE OF REVIEW: During critical illness, alterations of intestinal blood supply and inflammatory activation can result in severe intestinal hypoxia (limited oxygen availability). Conditions of hypoxia lead to the activation of a transcriptional program that is under the control of the transcription factor hypoxia-inducible factor (HIF). In many instances, HIF-dependent alterations of gene expression represent endogenous adaptive responses that dampen pathologic inflammation and could be targeted to treat intestinal injury. RECENT FINDINGS: Post-translational stabilization of the HIF transcription factor and corresponding changes in gene expression are central to the resolution of intestinal injury. Examples for such responses that we discuss in this review include hypoxia-elicited increases in extracellular adenosine production and signaling, particularly through the A2B adenosine receptor, and intestinal protection provided by hypoxia-inducible netrin-1. SUMMARY: The present review focuses on HIF-elicited anti-inflammatory pathways that result in intestinal protection during critical illness. Many of these pathways represent novel therapeutic targets for attenuating multiorgan failure and critical illness. Whereas these therapeutic approaches are currently being investigated in cell culture models or in genetic mouse models, we are optimistic that at least some of these novel targets can be translated from bench to bedside in the near future. PMID- 22322267 TI - Vascular endothelium as a target of diesel particulate matter-associated toxicants. PMID- 22322268 TI - What is the efficacy and safety of colistin for the treatment of ventilator associated pneumonia? A systematic review and meta-regression. AB - BACKGROUND: Experience with intravenous and aerosolized forms of colistin for the treatment of ventilator-associated pneumonia (VAP) in patients without cystic fibrosis is limited. We aimed to assess the safety and efficacy of colistin for the treatment of VAP. METHODS: We searched MEDLINE and Cochrane Database of Systematic Reviews for studies comparing colistin vs other antibiotics for treatment of VAP in patients without cystic fibrosis. QUOROM guidelines were followed, the I(2) method was used for heterogeneity, and a random-effects model for odds ratio (OR) estimates. RESULTS: Six controlled studies met the inclusion criteria. Clinical response did not differ significantly between colistin and control groups (OR, 1.14; 95% confidence interval [CI], .74-1.77; P = .56; I(2) = 0%). The efficacy of colistin was independent of study design (prospective OR, 0.89 [95% CI, .48-1.66; P = .71; I(2) = 0%]; retrospective OR, 1.45 [95% CI, .79 2.68; P = .23; I(2) = 0%]); randomized trials OR, 0.86 [95% CI, .43-1.74; P = .68; I(2) = 0%]). There was no indication of a significant change in clinical response after controlling for concomitant antibiotic treatment (intercept, 0.121; slope, 0.0315; P = .95). Treatment with colistin vs controls did not affect hospital mortality (OR, 0.92; 95% CI, .50-1.67; P = .78; I(2) = 34.59%) or nephrotoxicity (OR, 1.14; 95% CI, .59-2.20; P = .69; I(2) = 0%). Fourteen single arm studies have been analyzed, and the results were in concordance with the findings of the controlled studies. CONCLUSIONS: Our results suggest that colistin may be as safe and as efficacious as standard antibiotics for the treatment of VAP. PMID- 22322269 TI - Colistin in ventilator-associated pneumonia. PMID- 22322270 TI - Foot ulcer, skin nodules, and blurred vision. PMID- 22322272 TI - Hepatitis C clinic operated by infectious disease specialists at a comprehensive cancer center: help is on the way. PMID- 22322275 TI - Respiratory disease on cruise ships. PMID- 22322276 TI - Musical murmurs on internal carotid artery: sonological herald of vessel dissection? PMID- 22322277 TI - A novel C-5' substituted cinchona alkaloid-derived catalyst promotes additions of alkyl thiols to nitroolefins with excellent enantioselectivity. AB - A new bifunctional C-5' substituted cinchona alkaloid-based catalyst promotes the first highly enantioselective additions of alkyl thiols to nitrostyrenes. PMID- 22322278 TI - Distinct patterns of human medulloblastoma dissemination in the developing chick embryo nervous system. AB - Medulloblastoma (MB) is the most common malignant primary brain tumor in children. Aggressive tumors that disseminate along the leptomeninges carry extremely poor prognoses. Mechanisms that predict dissemination are poorly understood. Our objective was to develop a reliable and reproducible model to study MB dissemination. We have created a chicken-human xenograft to study features of MB with leptomeningeal dissemination. Human MB cell lines (D283, Daoy), primary human MB cells (SF8113), and primary genetic mouse model (Math1cre:SmoM2 flox/flox) MB cells were either transfected to express green fluorescent protein (GFP) or were labeled with a membrane permeable green fluorescent probe. Cells were then injected as aggregates or implanted as pellets into the developing chicken brain immediately after neural tube closure at embryonic day 2 (E2). Most embryos were harvested three days after implantation (E5) though some were harvested up to E15. The developing brain was analyzed via whole mount fluorescent imaging and tissue section immunohistochemistry. Human and mouse MBs survived in the developing chicken central nervous system (CNS). They exhibited distinct patterns of incorporation and dissemination into the CNS that were consistent with observed phenotypes of the corresponding human patient or mouse host. Specifically, metastatic D283 cells disseminated along the leptomeninges whereas Daoy, primary mouse MB, and primary human MB cells did not. This work supports an avian-human xenograft as a successful model to study patterns of MB dissemination. Our model provides a basis for manipulating cell signaling mechanisms to understand critical targets involved in MB dissemination. PMID- 22322279 TI - Tumor microenvironment: a main actor in the metastasis process. AB - Over recent decades, various studies have argued that the metastatic tissue microenvironment is fully controlled by the intrinsic properties of the cancer cells (growth, motility and invasion, angiogenesis, extracellular matrix remodeling, immune escape) and additional cells types. Overall, the extrinsic factors and determinants mediate the contribution of the host microenvironment to metastasis formation. The tumor microenvironment carries out these functions by secretion of molecules that can influence and modulate its phenotype, making these complex interactions the basis for support for the progression of a cancer. Here, we undertake a summary of the "state of the art" of the functions and actions of these cells, as the main actors in the promotion of the formation of the microenvironment of the metastatic niche, and the associated network of interactions. The unraveling of the relationships between tumorigenic cells and their microenvironment represents an important issue for the development of new therapeutic agents that can fight both initiation and recurrence of cancer. PMID- 22322280 TI - Neuroprotective effects of a taurine-containing irrigation solution for vitrectomy. AB - BACKGROUND: During pars plana vitrectomy, the retina is exposed to several iatrogenic risk factors, including excitotoxicity. A taurine-containing irrigation solution for pars plana vitrectomy (PURI PROTECT) has been developed and is claimed to have neuroprotective properties. METHODS: Retinal ganglion cells (RGC-5) and retinal whole mounts were incubated in standard irrigation solution (SIS) and SIS supplemented with 3 mM taurine (SIS-taurine). Excitotoxicity was induced by the addition of 8, 10, and 12 mM or 250 MUM glutamate. Cell viability and cell survival were assessed by the MTT test and Annexin-V/propidium iodide flow cytometry. Whole mounts were stained with the Live/Dead staining assay. Pars plana vitrectomy with SIS or SIS-taurine was performed in rabbits. Animals were followed-up by electroretinography. RESULTS: RGC-5 incubated in SIS-taurine showed a 4.3-fold (P < 0.0005) better overall cell viability and an up to 8.5-fold (P < 0.05) increased cell survival under excitotoxic conditions compared with that incubated in SIS. Whole mounts incubated in SIS-taurine showed a 1.7-fold (P < 0.0005) and 1.6-fold (P < 0.0005) better cell survival under excitotoxic and nonexcitotoxic conditions, respectively. In the immediate postoperative period, b-wave amplitudes were significantly better in animals operated with SIS-taurine compared with control (P < 0.01). CONCLUSION: A taurine-containing irrigation solution may protect retinal ganglion cells against excitotoxicity. PMID- 22322281 TI - Red blood cell distribution width as an independent predictor of all-cause mortality in out of hospital cardiac arrest. AB - OBJECTIVE: Post-resuscitation period is characterized by high early mortality due to post-cardiac arrest syndrome. Recent studies found that elevated red cell distribution width (RDW) is a strong predictor of mortality in critically ill patients. We investigated the prognostic significance of RDW in out-of-hospital cardiac arrest (OHCA) victims. METHODS: Analysis of emergency department OHCA registry extending from January 2007 to December 2010 was conducted. Patients with ROSC were assessed for Utstein predictors including sex, age, arrest location, presence of witness, bystander cardiopulmonary resuscitation, response time, initial rhythm and cause of arrest. RDW, hematocrit, white blood cell and platelet counts, blood urea nitrogen (BUN), creatinine and albumin were also obtained. Outcome variable was survival duration within 30 days. RDW was categorized in quartiles as <13.2%, 13.2% to 14.0%, 14.1% to 15.4% and >15.4%. Hazard ratios (HRs) were estimated using Cox-proportional hazard models in both univariate and multivariate analysis. All prognostic variables with their p value<0.1 in univariate analysis were used in multivariate analysis for adjustment. RESULTS: Among 409 OHCA patients, 219 patients had ROSC. Highest RDW quartile (RDW>15.4%), female sex, older age, non-shockable initial rhythm, increased BUN and creatinine and decreased albumin, hematocrit and platelet count were associated with increased mortality in univariate analysis. In multivariate analysis, the highest RDW quartile was independently associated with all-cause mortality (HR=1.95; 95% CI 1.05-3.60; p=0.034) during 30-day post-resuscitation period. Other significant variables were age, initial rhythm and serum albumin. CONCLUSIONS: Initial RDW is an independent predictor of all-cause mortality in post-resuscitation patients. PMID- 22322282 TI - Hyperoxia post-cardiac arrest - The debate continues? PMID- 22322283 TI - Primary respiratory arrest recognised by emergency medical technicians and followed by cardiac arrest in Japan: identification of a subgroup of EMT witnessed cardiac arrests with an extremely poor outcome. AB - REVIEW: Some unconscious patients are found to be in primary respiratory arrest (PRA) by emergency medical technicians (EMTs). In contrast to citizens, EMTs manage PRA with artificial ventilation but not with cardiopulmonary resuscitation (CPR). This study aimed to investigate the characteristics and outcomes of PRA prior to EMT arrival and compare these data with those of a PRA-related group: patients with out-of-hospital cardiac arrests (OHCAs). METHODS: Baseline data were prospectively collected by fire departments for their adult (16 years or older) OHCA and PRA patients from April 2003 through March 2010. We extracted those who had PRA prior to EMT arrival. The EMT- and bystander-witnessed OHCA patients who underwent CPR were also extracted as control groups. RESULTS: There were 178 cases of PRA prior to EMT arrival. The majority (164/178) of these individuals were in a deep coma and met the criteria for the initiation of bystander CPR. Approximately 61% (108/178) of these PRAs were followed by cardiac arrests, which were classified as EMT-witnessed OHCAs by the Utstein template. The EMTs manually ventilated the patients until the cardiac arrest occurred. The 1-Y survival of this subgroup was the lowest of the PRA and PRA-related OHCA subgroups and was significantly lower than that of bystander-witnessed OHCAs with bystander CPR, when trauma and terminal illness cases were excluded (adjusted odds ratio=3.888 (1.103-24.827)). CONCLUSIONS: We identified a subgroup of PRAs with unexpectedly poor outcomes. The BLS guidelines for healthcare providers including EMTs should be re-evaluated by a large prospective study. PMID- 22322284 TI - A feasibility study evaluating the role of cerebral oximetry in predicting return of spontaneous circulation in cardiac arrest. AB - To date there has been no reliable noninvasive real time monitoring available to determine cerebral perfusion during cardiac arrest. OBJECTIVES: To investigate the feasibility of using a commercially available cerebral oximeter during in hospital cardiac arrest, and determine whether this parameter predicts return of spontaneous circulation (ROSC). METHODS: Cerebral oximetry was incorporated in cardiac arrest management in 19 in-hospital cardiac arrest cases, five of whom had ROSC. The primary outcome measure was the relationship between rSO(2) and ROSC. RESULTS: The use of cerebral oximetry was found to be feasible during in hospital cardiac arrest and did not interfere with management. Patients with ROSC had a significantly higher overall mean +/- SE rSO(2) (35 +/- 5 vs. 18 +/- 0.4, p<0.001). The difference in mean rSO(2) between survivors and non-survivors was most pronounced in the final 5 min of cardiac arrest (48 +/- 1 vs. 15 +/- 0.2, p<0.0001) and appeared to herald imminent ROSC. Although spending a significantly higher portion of time with an rSO(2)>40% was found in survivors (p<0.0001), patients with ROSC had an rSO(2) above 30% for >50% of the duration of cardiac arrest, whereas non-survivors had an rSO(2) that was below 30%>50% of their cardiac arrest. Patients with ROSC also had a significantly higher change in rSO(2) from baseline compared to non-survivors (310% +/- 60% vs. 150% +/- 27%, p<0.05). CONCLUSION: Cerebral oximetry may have a role in predicting ROSC and the optimization of cerebral perfusion during cardiac arrest. PMID- 22322285 TI - A high-temporal resolution algorithm to discriminate shockable from nonshockable rhythms in adults and children. AB - AIM: To design the core algorithm of a high-temporal resolution rhythm analysis algorithm for automated external defibrillators (AEDs) valid for adults and children. Records from adult and paediatric patients were used all together to optimize and test the performance of the algorithm. METHODS: A total of 574 shockable and 1126 nonshockable records from 1379 adult patients, and 57 shockable and 503 nonshockable records from 377 children aged between 1 and 8 years were used. The records were split into two groups for development and testing. The core algorithm analyses ECG segments of 3.2s duration and classifies the segments as nonshockable or likely shockable combining a time, slope and frequency domain analysis to detect normally conducted QRS complexes. RESULTS: The algorithm correctly identified 98% of nonshockable segments, 97.5% in adults and 98.4% in children, and identified 99.5% of shockable segments as likely shockable, 100% in adults and 96% in children. When likely shockable segments were further analysed in terms of regularity, spectral content and heart rate to form a complete rhythm analysis algorithm the overall specificity increased to 99.6% and the sensitivity was 99.1%. CONCLUSION: Paediatric and adult rhythms can be accurately diagnosed using 3.2s ECG segments. A single algorithm safe for children and adults can simplify AED use, and its high temporal resolution shortens pre-shock pauses which may contribute to improve resuscitation outcome. PMID- 22322286 TI - Auditing resuscitation of preterm infants at birth by recording video and physiological parameters. AB - OBJECTIVE: To evaluate compliance with neonatal resuscitation guidelines during resuscitation of preterm infants by video recording of delivery room management and monitoring physiologic parameters. METHODS: The delivery room management of preterm infants at birth was recorded by an independent researcher. Physiological parameters (airway pressures, gas flow, tidal volume, heart rate and oxygen saturation) were measured, use of supplemental oxygen was noted and a video of the resuscitation was recorded. All signals were digitised and recorded using specially designed software. The delivery room management was then evaluated and compared with the local resuscitation guidelines. RESULTS: Thirty-four infants were included with a mean (SD) gestational age of 30.6 (3.2) weeks and birth weight of 1292 (570) g. Time from birth to initial evaluation was longer than recommended (65 (15) s). Respiratory support was started at 70 (23) s. In 7/34 infants (21%), interventions were performed according to guidelines. In 25/34 infants (74%), one or more respiratory interventions were not performed according to guidelines. In 10/34 infants (29%), one or more non-respiratory interventions (mainly related to the prevention of heat loss) were not performed according to guidelines. The presence and adequacy of spontaneous breathing was difficult to judge clinically. In almost all occasions (96%) the information from the respiratory function monitor was not used. CONCLUSIONS: Neonatal caregivers often deviate from resuscitation guidelines. Respiratory function monitoring parameters were often not used during resuscitation. A difficult part of neonatal resuscitation is subjectively assessing spontaneous breathing. PMID- 22322287 TI - Efficacy of veno-arterial extracorporeal membrane oxygenation in acute myocardial infarction with cardiogenic shock. AB - AIM: We analyzed the results of acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) necessitating extracorporeal membrane oxygenation (ECMO), and investigated for the associated risk factors for poor clinical outcomes. METHODS: We retrospectively reviewed the medical records of 27 patients who required ECMO for AMI associated with CS between April 2006 and July 2010. Mean age was 63.7 +/- 11.0 (range: 45-81) years, and there were 16 males (59.3%). RESULTS: The mean duration of ECMO support was 30.2 +/- 30.1 (range: 1-141)h. Cardiopulmonary resuscitations (CPR) were performed in 21 patients (77.8%) before ECMO initiation. Twenty-two patients (81.5%) were successfully weaned off ECMO, and 16 patients (59.3%) survived to discharge. The 30-day mortality was 37.0% (10/27 patients). Complications developed in 17 patients (63.0%: pneumonia in 10 patients, acute renal failure in 10 patients, massive bleeding in 4 patients, and thromboembolic event in 1 patient). The period between CPR initiation and ECMO commencement was a significant risk factor for ECMO weaning failure. High pre ECMO serum lactate level was identified as a significant risk factor for poor survival on univariated and multivariated analysis. CONCLUSION: ECMO support could improve survival in patients who suffer AMI associated with CS, and early ECMO initiation yields better outcomes (successful ECMO weaning). PMID- 22322288 TI - Letter to the editor. PMID- 22322289 TI - Biosorption of strontium from aqueous solution by fungus Aspergillus terreus. AB - INTRODUCTION: The biosorption characteristics of strontium ions using fungus Aspergillus terreus were investigated. Experimental parameters affecting the biosorption process such as pH, contact time, initial metal concentration, and temperature were studied. MATHEMATICAL DESCRIPTION: Fungus A. terreus exhibited the highest strontium uptake capacity at 15 degrees C at an initial strontium ion concentration of 876 mg L(-1) and an initial pH of 9. Biosorption capacity increased from 219 to 308 mg g(-1) with a decrease in temperature from 45 degrees C to 15 degrees C at this initial strontium concentration. The equilibrium data fitted very well to the Langmuir adsorption model in the concentration range of strontium ions and at all the temperatures studied. CONCLUSION: Evaluation of the experimental data in terms of biosorption dynamics showed that the biosorption of strontium onto fungus followed the pseudo-second-order dynamics well (R(2) > 0.985). The calculated thermodynamics parameters (-1.64 < ?G degrees < -1.93 kJ mol(-1) at temperatures of 45-15 degrees C, ?H degrees = -4.83 kJ mol(-1) and ?S degrees = -0.01 kJ mol(-1) K(-1)) showed that the biosorption of strontium ions were feasible, spontaneous, and exothermic at the temperature ranges of 15-45 degrees C. PMID- 22322290 TI - Standardized emissions inventory methodology for open-pit mining areas. AB - INTRODUCTION: There is still interest in a unified methodology to quantify the mass of particulate material emitted into the atmosphere by activities inherent to open-pit mining. For the case of total suspended particles (TSP), the current practice is to estimate such emissions by developing inventories based on the emission factors recommended by the USEPA for this purpose. However, there are disputes over the specific emission factors that must be used for each activity and the applicability of such factors to cases quite different to the ones under which they were obtained. There is also a need for particulate matter with an aerodynamic diameter less than 10 MUm (PM(10)) emission inventories and for metrics to evaluate the emission control programs implemented by open-pit mines. STANDARDIZED EMISSION INVENTORY METHODOLOGY: To address these needs, work was carried out to establish a standardized TSP and PM(10) emission inventory methodology for open-pit mining areas. The proposed methodology was applied to seven of the eight mining companies operating in the northern part of Colombia, home to the one of the world's largest open-pit coal mining operations (~70 Mt/year). RESULTS: The results obtained show that transport on unpaved roads is the mining activity that generates most of the emissions and that the total emissions may be reduced up to 72% by spraying water on the unpaved roads. Performance metrics were defined for the emission control programs implemented by mining companies. It was found that coal open-pit mines are emitting 0.726 and 0.180 kg of TSP and PM(10), respectively, per ton of coal produced. It was also found that these mines are using on average 1.148 m(2) of land per ton of coal produced per year. PMID- 22322291 TI - Pesticide pressure and fish farming in barrage pond in Northeastern France Part I: site characterization and water quality. AB - PURPOSE: Fish farming in barrage pond is a rearing system commonly used worldwide. Obtaining good water quality is essential to improve sustainability of these ecosystems, both for health of fish consumers and environmental considerations. However, ponds are often located in agricultural landscape, but few study reports impact of pesticide pressure on these ecosystems. This study characterizes five sites in Northeastern France. This work establishes an initial framework for pesticide monitoring with the aim to improve understanding of the fate of pesticides in ponds. METHODS: This framework is based on surveys indicating managements and Geographical Information System (GIS) for five ponds and their watersheds (sites: C-0, C-25, C-45, C-75 and C-85) and completes with some analysis of a large spectrum of pesticide residues in surface waters. RESULTS: Watersheds show a gradient of crop proportion ranging from 0% to 82% of the watershed area, mainly rapeseed, wheat, barley and maize. Ponds were representative of local Northeastern France management. Many pesticides, and also nutrients, were measured in water with concentrations varying between sites and seasons. The sum of quantified molecules ranged from 0.17 MUg/l for site C-0 (March) to 8.81 MUg/l for site C-25 (October). Concentrations of metaldehyde, quinmerac, isoproturon and bentazon were sometimes above 1 MUg/l. CONCLUSIONS: There is a strong connection between pond and watershed, due to water supply throughout the fish production cycle. Sites with small pond/big watershed are the most exposed to acute contamination a few days after spraying because water discharges are not diluted. PMID- 22322292 TI - Occupational exposure to formaldehyde in an institute of morphology in Brazil: a comparison of area and personal sampling. AB - BACKGROUND, AIMS, AND SCOPE: Formaldehyde (FA) is a harmful chemical, which is classified as carcinogenic to humans (Group 1) by the International Agency for Research on Cancer. Solutions of FA that are used to preserve cadavers in research and education morphological institutes represent a risk to occupational health of professionals and students. During the dissection of cadavers in the anatomy laboratories, FA vapors are emitted, resulting in the exposure of students and their instructors to elevated levels of FA. The World Health Organization recommends an air quality guideline value of 0.1 mg m(-3) for exposure to FA. The limit of occupational exposure adopted by the Brazilian legislation (2.3 mg m(-3)) is markedly higher than those adopted by institutions of other countries around the world. The purpose of this study was to determine the levels of personal exposure and the area concentration of FA in the morphology department of the Federal Fluminense University, Brazil, and investigate and compare the relationship between them. METHODS: Four rooms distributed in the three floors of the Morphology Department were evaluated: the embalming laboratory, the anatomy laboratories, the corridor of the teachers' rooms, and the entrance hall. Thirty-six samples in total were collected in the second semester of 2010 and first semester of 2011. The air sampling and FA analysis were performed according to the EPA TO-11A Protocol, using a diffusive sampling device for carbonyl compounds. Personal samples were collected from monitors using a sampling device pinned on each person's lapel. The samples were analyzed using rapid resolution liquid chromatography with UV-DAD detection at 360 nm. RESULTS AND DISCUSSION: The concentrations of FA ranged from 0.20 and 0.18 mg m(-3) in the corridor between the teachers' rooms, 0.03 to 0.37 mg m(-3) in the entrance hall, 0.22 to 2.07 mg m(-3) in the anatomy laboratory, 2.21 to 2.52 mg m(-3), in the embalming room. The levels found in the corridor between the teachers' rooms and in the entrance hall were lower than in other compartments because of their large distances to the sources of FA and better ventilation. The other rooms presented higher levels of FA because of the activities carried there (embalming and dissection procedures). Even in the rooms that showed the lowest levels of FA, the values found were higher than those established by all international guideline limits, except the Brazilian legislation limit, although, the concentration level in the embalming room was even greater than the Brazilian guideline. These concentrations are 100-1,000 fold higher than those reported in an FA outdoor study. The exposure levels of monitors and students ranged from 1.89 to 4.82 mg m(-3), indicating that current practices at the Morphology Department at the university would represent a health risk. The simultaneous monitoring of area concentrations and personal exposure showed that the characteristics of classes and of cadavers' parts, the number of students in the room and even the activities of the monitors influence the FA concentrations. CONCLUSION: This study revealed that the concentration of FA was low in the ventilated areas of the Morphology Department, and that the personal exposure when the person was close to the cadavers during the dissection procedure was higher than the mean FA concentration. This should be considered in the risk assessment of FA during these activities without effective protection equipment. It is suggested that the Brazilian legislation of exposure to formaldehyde requires an urgent update considering international legislation. PMID- 22322293 TI - Identification of volatiles from Pinus silvestris attractive for Monochamus galloprovincialis using a SPME-GC/MS platform. AB - INTRODUCTION: A myriad of volatile organic compounds (VOCs) released by terrestrial vegetation plays an important role in environmental sciences. A thorough chemical identification of these species at the molecular level is essential in various fields, ranging from atmospheric chemistry to ecology of forest ecosystems. In particular, the recognition of VOCs profiles in a context of plant-insect communication is a key issue for the development of forest protection tools. PURPOSE: This work was aimed at the development of a simple, robust and reliable method for the identification of volatiles emitted from plant materials, which can attract or deter pest insects. Specifically, volatiles emitted from the bark of Pinus sylvestris were studied, which might attract the black pine sawyer beetle Monochamus galloprovincialis-a serious pest of the tree and a vector of a parasitic nematode Bursaphelenchus xylophius. METHOD: The volatiles from bark samples were collected using a solid-phase micro-extraction technique, and subsequently analysed by gas-chromatography/mass-spectrometry (GC/MS). The characterisation of the volatile fraction was based on the comparison with data in mass spectral libraries, and in most cases, with the available authentic standards. The identified compounds were screened against the available entomological data to select insect attractors. RESULTS: The identified components included terpenes (alpha-pinene, ?-3-carene, and para-cymenene), oxygenated terpenes (alpha-terpineol and verbenone), sesquiterpenes (alpha longipinene, longifolene, E-beta-farnesene, gamma-cadinene and pentadecane), and diterpenes (manoyl oxide and (+)-pimaral). Of these, longifolene and (+)-pimaral are of particular interest as plausible attractors for the M. galloprovincialis beetle that might find application in the construction of insect bait traps. PMID- 22322294 TI - Channel selective tunnelling through a nanographene assembly. AB - We report selective tunnelling through a nanographene intermolecular tunnel junction achieved via scanning tunnelling microscope tip functionalization with hexa-peri-hexabenzocoronene (HBC) molecules. This leads to an offset in the alignment between the energy levels of the tip and the molecular assembly, resulting in the imaging of a variety of distinct charge density patterns in the HBC assembly, not attainable using a bare metallic tip. Different tunnelling channels can be selected by the application of an electric field in the tunnelling junction, which changes the condition of the HBC on the tip. Density functional theory-based calculations relate the imaged HBC patterns to the calculated molecular orbitals at certain energy levels. These patterns bear a close resemblance to the pi-orbital states of the HBC molecule calculated at the relevant energy levels, mainly below the Fermi energy of HBC. This correlation demonstrates the ability of an HBC functionalized tip as regards accessing an energy range that is restricted to the usual operating bias range around the Fermi energy with a normal metallic tip at room temperature. Apart from relating to molecular orbitals, some patterns could also be described in association with the Clar aromatic sextet formula. Our observations may help pave the way towards the possibility of controlling charge transport between organic interfaces. PMID- 22322295 TI - Ack1 tyrosine kinase activation correlates with pancreatic cancer progression. AB - Pancreatic cancer is a significant cause of cancer mortality worldwide as the disease has advanced significantly in patients before symptoms are evident. The signal transduction pathways that promote this rapid progression are not well understood. Ack1 or TNK2, an ubiquitously expressed oncogenic non-receptor tyrosine kinase, integrates signals from ligand-activated receptor tyrosine kinases to modulate intracellular signaling cascades. In the present study, we investigated the Ack1 activation profile in a pancreatic cancer tumor microarray, and observed that expression levels of activated Ack1 and pTyr284-Ack1 positively correlated with the severity of disease progression and inversely correlated with the survival of patients with pancreatic cancer. To explore the mechanisms by which Ack1 promotes tumor progression, we investigated the role of AKT/PKB, an oncogene and Ack1-interacting protein. Ack1 activates AKT directly in pancreatic and other cancer cell lines by phosphorylating AKT at Tyr176 to promote cell survival. In addition, the Ack1 inhibitor AIM-100 not only inhibited Ack1 activation but also suppressed AKT tyrosine phosphorylation, leading to cell cycle arrest in the G1 phase. This effect resulted in a significant decrease in the proliferation of pancreatic cancer cells and induction of apoptosis. Collectively, our data indicate that activated Ack1 could be a prognostic marker for ascertaining early or advanced pancreatic cancer. Thus, Ack1 inhibitors hold promise for therapeutic intervention to inhibit pancreatic tumor growth. PMID- 22322296 TI - Altered angiogenesis in caveolin-1 gene-deficient mice is restored by ablation of endothelial nitric oxide synthase. AB - Caveolin-1 is an essential structural protein of caveolae, specialized plasma membrane organelles highly abundant in endothelial cells, where they regulate multiple functions including angiogenesis. Caveolin-1 exerts a tonic inhibition of endothelial nitric oxide synthase (eNOS) activity. Accordingly, caveolin-1 gene-disrupted mice have enhanced eNOS activity as well as increased systemic nitric oxide (NO) levels. We hypothesized that excess eNOS activity, secondary to caveolin deficiency, would mediate the decreased angiogenesis observed in caveolin-1 gene-disrupted mice. We tested tumor angiogenesis in mice lacking either one or both proteins, using in vitro, ex vivo, and in vivo assays. We show that endothelial cell migration, tube formation, cell sprouting from aortic rings, tumor growth, and angiogenesis are all significantly impaired in both caveolin-1-null and eNOS-null mice. We further show that these parameters were either partially or fully restored in double knockout mice that lack both caveolin-1 and eNOS. Furthermore, the effects of genetic ablation of eNOS are mimicked by the administration of the NOS inhibitor N-nitro-L-arginine methyl ester hydrochloride (L-NAME), including the reversal of the caveolin-1-null mouse angiogenic phenotype. This study is the first to demonstrate the detrimental effects of unregulated eNOS activity on angiogenesis, and shows that impaired tumor angiogenesis in caveolin-1-null mice is, at least in part, the result of enhanced eNOS activity. PMID- 22322297 TI - STAT3-mediated signaling dysregulates lung fibroblast-myofibroblast activation and differentiation in UIP/IPF. AB - STAT3 is a latent transcription factor that plays a role in regulating fibroblast function in fibrotic lung diseases. To further understand the role of STAT3 in the phenotypic divergence and function of human lung fibroblasts (LFs), we investigated the effect of basal and cytokine-induced STAT3 activity on indices of LF differentiation and activation, including expression of alpha-smooth muscle actin (alpha-SMA), collagen, and adhesion molecules Thy-1/CD90 and alpha(v) beta(3) and beta(5) integrins. We identified a population of fibroblasts from usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) lungs characterized by constitutively phosphorylated STAT3, lower proliferation rates, and diminished expression of alpha-SMA, Thy-1/CD90, and beta(3) integrins compared with control LFs. Staining of UIP lung biopsy specimens demonstrated that phosphorylated STAT3 was not present in alpha-SMA-positive fibroblastic foci but was observed in the nuclei of cells located in the areas of dense fibrosis. STAT3 activation in LFs did not significantly influence basal or transforming growth factor beta(1)-induced collagen I expression but inhibited expression of alpha-SMA, Thy-1/CD90, and alphav beta(3) integrins. Suppression of STAT3 signaling diminished resistance of IPF LFs to staurosporine-induced apoptosis and responsiveness to transforming growth factor beta(1) but increased basal alpha SMA and restored beta(3) integrin expression in LFs via an ALK-5-dependent, SMAD3/7-independent mechanism. These data suggest that STAT3 activation regulates several pathways in human LFs associated with normal wound healing, whereas aberrant STAT3 signaling plays a critical role in UIP/IPF pathogenesis. PMID- 22322298 TI - Dorsal root ganglia damage in SIV-infected rhesus macaques: an animal model of HIV-induced sensory neuropathy. AB - HIV-associated sensory neuropathy (HIV-SN) is currently the most common neurological complication of chronic HIV infection and continues to substantially affect patient quality of life. Mechanisms underlying the neuronal damage and loss observed in sensory ganglia of HIV-infected individuals have not been sufficiently studied. The present study aimed to develop and characterize a model of HIV-SN using SIV-infected CD8 T-lymphocyte-depleted rhesus macaques (Macaca mulatta). Uninfected controls (n = 5), SIV-infected CD8-depleted (n = 4), and SIV infected non-CD8-depleted (n = 6) animals were used. Of the six non-CD8-depleted animals, three were conventional progressors (progressing to AIDS >1 year after infection) and three were rapid progressors (AIDS within 6 months). Dorsal root ganglia (DRG) were examined for histological hallmarks of HIV-SN, including satellitosis, presence of Nageotte nodules, and neuronophagia, as well as increased numbers of CD68(+) macrophages and abundant viral replication. In contrast to non-CD8-depleted animals, which had mild to moderate DRG pathology, the CD8-depleted SIV-infected animals had moderate to severe DRG damage, with increased numbers of CD68(+) satellite cells. Additionally, there was marked active viral replication in the affected DRG. These findings confirm that many features of HIV-SN can be recapitulated in the CD8-depleted SIV-infected rhesus macaque model within a short time frame and illustrate the importance of this model for study of sensory neuropathy. PMID- 22322299 TI - Overexpression of tumor necrosis factor-alpha in the lungs alters immune response, matrix remodeling, and repair and maintenance pathways. AB - Increased production of tumor necrosis factor (TNF)-alpha and matrix metalloproteinases (MMPs) is a feature of inflammatory lung diseases, including emphysema and fibrosis, but the divergent pathological characteristics that result indicate involvement of other processes in disease pathogenesis. Transgenic mice overexpressing TNF-alpha in type II alveolar epithelial cells under the control of the surfactant protein (SP)-C promoter develop pulmonary inflammation and emphysema but are resistant to induction of fibrosis by administration of bleomycin or transforming growth factor-beta. To study the molecular mechanisms underlying the development of this phenotype, we used a microarray approach to characterize the pulmonary transcriptome of SP-C/TNF-alpha mice and wild-type littermates. Four-month-old SP-C/TNF-alpha mice displayed pronounced pulmonary inflammation, airspace enlargement, increased MMP-2 and MMP 9 levels, and altered expression of 2332 probes. The functional assessment of genes with increased expression revealed enrichment of inflammatory/immune responses and proteases, whereas genes involved in protease inhibition, angiogenesis, cross-linking of basement membrane proteins, and myofibroblast differentiation were predominantly decreased. Comparison with multiple lung disease models identified a set of genes unique to the SP-C/TNF-alpha model and revealed that lack of extracellular matrix production distinguished SP-C/TNF alpha mice from fibrosis models. Activation of inflammatory and proteolytic pathways and disruption of maintenance and repair processes are central features of emphysema in this TNF-overexpression model. Impairment of myofibroblast differentiation and extracellular matrix production may underlie resistance to induction of fibrosis. PMID- 22322300 TI - Intestinal mast cell levels control severity of oral antigen-induced anaphylaxis in mice. AB - Food-triggered anaphylaxis can encompass a variety of symptoms that affect multiple organ systems and can be life threatening. The molecular distinction between non-life-threatening and life-threatening modes of such anaphylaxis has not yet been delineated. In this study, we sought to identify the specific immune functions that regulate the severity of oral antigen-induced anaphylaxis. We thus developed an experimental mouse model in which repeated oral challenge of ovalbumin-primed mice induced an FcepsilonRI- and IgE-dependent oral antigen triggered anaphylaxis that involved multiple organ systems. Strikingly, the severity of the systemic symptoms of anaphylaxis (eg, hypothermia) positively correlated with the levels of intestinal mast cells (r = -0.53; P < 0.009). In addition, transgenic mice with both increased intestinal and normal systemic levels of mast cells showed increased severity of both intestinal and extra intestinal symptoms of IgE-mediated passive as well as oral antigen- and IgE triggered anaphylaxis. In conclusion, these observations indicate that the density of intestinal mast cells controls the severity of oral antigen-induced anaphylaxis. Thus, an awareness of intestinal mast cell levels in patients with food allergies may aid in determining their susceptibility to life-threatening anaphylaxis and may eventually aid in the treatment of food-triggered anaphylaxis. PMID- 22322301 TI - Laminin-111 protein therapy reduces muscle pathology and improves viability of a mouse model of merosin-deficient congenital muscular dystrophy. AB - Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is a lethal muscle-wasting disease that is caused by mutations in the LAMA2 gene, resulting in the loss of laminin-alpha2 protein. MDC1A patients exhibit severe muscle weakness from birth, are confined to a wheelchair, require ventilator assistance, and have reduced life expectancy. There are currently no effective treatments or cures for MDC1A. Laminin-alpha2 is required for the formation of heterotrimeric laminin-211 (ie, alpha2, beta1, and gamma1) and laminin-221 (ie, alpha2, beta2, and gamma1), which are major constituents of skeletal muscle basal lamina. Laminin-111 (ie, alpha1, beta1, and gamma1) is the predominant laminin isoform in embryonic skeletal muscle and supports normal skeletal muscle development in laminin-alpha2-deficient muscle but is absent from adult skeletal muscle. In this study, we determined whether treatment with Engelbreth-Holm-Swarm-derived mouse laminin-111 protein could rescue MDC1A in the dy(W-/-) mouse model. We demonstrate that laminin-111 protein systemically delivered to the muscles of laminin-alpha2-deficient mice prevents muscle pathology, improves muscle strength, and dramatically increases life expectancy. Laminin-111 also prevented apoptosis in laminin-alpha2-deficient mouse muscle and primary human MDC1A myogenic cells, which indicates a conserved mechanism of action and cross reactivity between species. Our results demonstrate that laminin-111 can serve as an effective protein substitution therapy for the treatment of muscular dystrophy in the dy(W-/-) mouse model and establish the potential for its use in the treatment of MDC1A. PMID- 22322302 TI - Macrophage beta2 integrin-mediated, HuR-dependent stabilization of angiogenic factor-encoding mRNAs in inflammatory angiogenesis. AB - HuR is a member of the Drosophila Elav protein family that binds mRNA degradation sequences and prevents RNase-mediated degradation. Such HuR-mediated mRNA stabilization, which is stimulated by integrin engagement and is controlled at the level of HuR nuclear export, is critically involved in T-cell cytokine production. However, HuR's role in macrophage soluble factor production, in particular in response to angiogenic stimuli, has not yet been established. We show that the labile transcripts that encode vascular endothelial growth factor and matrix metalloproteinase-9 are stabilized when murine macrophages adhere to the beta(2) integrin ligand intercellular adhesion molecule-1. This mRNA stabilization response was absent in bone marrow-derived macrophages obtained from conditional macrophage-specific HuR knockout mice. The microvascular angiogenic response to an inflammatory stimulus (ie, subcutaneous polyvinyl alcohol sponge implantation) was markedly diminished in these macrophage HuR knockout mice despite the equal levels of macrophage localization to those observed in littermate wild-type controls. Furthermore, blood flow recovery and ischemic muscle neovascularization after femoral artery ligation were impaired in the conditional macrophage-specific HuR knockout mice. These results demonstrate that dynamic effects on mRNA, mediated by the RNA-binding and RNA-stabilizing protein HuR, are required for macrophage production of angiogenic factors, which play critical roles in the neovascular responses to a variety of stimuli, including tissue ischemia. PMID- 22322303 TI - Rapid histamine-induced neutrophil recruitment is sphingosine kinase-1 dependent. AB - Leukocyte recruitment to sites of inflammation is critical for the development of acute allergic responses. Rapid P-selectin up-regulation by endothelial cells is a key promoter of leukocyte infiltration in response to mediators such as histamine. However, the mechanisms underpinning this process are still incompletely understood. We examined the role of the sphingosine kinase/sphingosine-1-phosphate (SK/S1P) pathway and showed that in human umbilical vein endothelial cells, histamine rapidly activates SK in an extracellular signal-regulated kinase (ERK) 1/2-dependent manner, concurrent with the induction of P-selectin expression. Histamine activated both SK-1 and SK-2 isoforms; inhibition of SK-1, but not SK-2, attenuated histamine-induced P selectin up-regulation and neutrophil rolling in vitro. S1P receptor antagonists failed to prevent histamine-induced P-selectin expression, and exogenous S1P did not increase P-selectin expression, suggesting that S1P cell surface receptors are not involved in this process. Finally, the role of both SK-1 and SK-2 in histamine-induced leukocyte rolling in vivo was assessed using pharmacological and genetic methods. Consistent with the in vitro findings, mice pretreated with either sphingosine kinase inhibitor or fingolimod (FTY720) significantly attenuated histamine-induced leukocyte rolling in the cremaster muscle. Similarly, Sphk1(-/-) but not Sphk2(-/-) mice exhibited reduced histamine-induced leukocyte rolling. These findings demonstrate a key role for SK-1 in histamine induced rapid P-selectin up-regulation and associated leukocyte rolling, and suggest that endothelial SK-1 is an important contributor to allergic inflammation. PMID- 22322304 TI - The Gne M712T mouse as a model for human glomerulopathy. AB - Pathological glomerular hyposialylation has been implicated in certain unexplained glomerulopathies, including minimal change nephrosis, membranous glomerulonephritis, and IgA nephropathy. We studied our previously established mouse model carrying a homozygous mutation in the key enzyme of sialic acid biosynthesis, N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. Mutant mice died before postnatal day 3 (P3) from severe glomerulopathy with podocyte effacement and segmental glomerular basement membrane splitting due to hyposialylation. Administration of the sialic acid precursor N-acetylmannosamine (ManNAc) led to improved sialylation and survival of mutant pups beyond P3. We determined the onset of the glomerulopathy in the embryonic stage. A lectin panel, distinguishing normally sialylated from hyposialylated glycans, used WGA, SNA, PNA, Jacalin, HPA, and VVA, indicating glomerular hyposialylation of predominantly O-linked glycoproteins in mutant mice. The glomerular glycoproteins nephrin and podocalyxin were hyposialylated in this unique murine model. ManNAc treatment appeared to ameliorate the hyposialylation status of mutant mice, indicated by a lectin histochemistry pattern similar to that of wild-type mice, with improved sialylation of both nephrin and podocalyxin, as well as reduced albuminuria compared with untreated mutant mice. These findings suggest application of our lectin panel for categorizing human kidney specimens based on glomerular sialylation status. Moreover, the partial restoration of glomerular architecture in ManNAc-treated mice highlights ManNAc as a potential treatment for humans affected with disorders of glomerular hyposialylation. PMID- 22322305 TI - Atomic identification of fluorescent Q-dots on tau-positive fibrils in 3D reconstructed pick bodies. AB - Pick body disease, characterized by the presence of Pick bodies, is distinguished from neurofibrillary tangles in Alzheimer disease on the basis of their smooth, spherical shape. Quantum dots (QDs) are nanometer-scale, water-soluble fluorophores that are detectable both as a fluorescent signal by light microscopy and as electron-dense particles under electron microscopy. In this study, tau positive Pick bodies were immunofluorescently labeled with QD nanocrystals composed of cadmium selenide for three-dimensional (3D) reconstruction and subsequently subjected to electron microscopic observation to identify QD immunolabeling on the same Pick body for comparison in detail. The identity of the QD nanocrystals, which label the tau-positive fibrils, was confirmed by the presence of both cadmium and selenium on these nanocrystals, demonstrated as parallel peaks corresponding to these atoms on energy-dispersive X-ray spot analysis under super-resolution scanning transmission electron microscopy. This confirmation of the specificity of the QD labeling through both its fluorescence and energy-dispersive X-ray spectra reinforces the reliability of the labeling. In addition, this exact comparison of the same structure by electron microscopy and 3D light microscopy demonstrates how its ultrastructural details are related to its surrounding structures on a 3D basis, providing further insights into how molecules woven into specific pathological ultrastructures are at work in situ. PMID- 22322306 TI - The Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein, a toll-like receptor 4 agonist, enhances dendritic cell-based cancer vaccine potency. AB - In this study, we showed the direct interaction between Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein (FAP) and toll-like receptor4 (TLR4) via co-localization and binding by using confocal microscopy and co-immunoprecipitation assays. FAP triggered the expression of pro- and antiinflammatory cytokines in a TLR4-dependent manner. In addition, FAP-induced cytokine expression in bone marrow-derived dendritic cells (BMDCs) was modulated in part by glycogen synthase kinase-3 (GSK-3). FAP-induced expression of CD80, CD86, major histocompatibility complex (MHC) class I, and MHC class II in TLR4(+/+) BMDCs was not observed in TLR4(-/-) BMDCs. Furthermore, FAP induced DC mediated CD8(+) T cell proliferation and cytotoxic T lymphocyte (CTL) activity, and suppressed tumor growth with DC-based tumor vaccination in EG7 thymoma murine model. Taken together, these results indicate that the TLR4 agonist, FAP, a potential immunoadjuvant for DC-based cancer vaccination, improves the DC-based immune response via the TLR4 signaling pathway. PMID- 22322307 TI - Different roles and different results: how activity orientations correspond to relationship quality and student outcomes in school-based mentoring. AB - This prospective, mixed-methods study investigated how the nature of joint activities between volunteer mentors and student mentees corresponded to relationship quality and youth outcomes. Focusing on relationships in school based mentoring programs in low-income urban elementary schools, data were obtained through pre-post assessments, naturalistic observations, and in-depth interviews with mentors and mentees. Adopting an exploratory approach, the study employed qualitative case study methods to inductively identify distinctive patterns reflecting the focus of mentoring activities. The activity orientations of relationships were categorized according to the primary functional role embodied by the mentor and the general theme of interactions: teaching assistant/tutoring, friend/engaging, sage/counseling, acquaintance/floundering. Next, these categories were corroborated by comparing the groups on quantitative assessments of relationship quality and change in child outcomes over time. Relationships characterized by sage mentoring, which balanced amicable engagement with adult guidance, were rated most favorably by mentees on multiple measures of relationship quality. Furthermore, students involved in sage mentoring relationships showed declines in depressive symptoms and aggressive behaviors. For disconnected pairs (acquaintances), students reported more negative relationship experiences. Findings suggest effective mentoring relationships represent a hybrid between the friendly mutuality of horizontal relationships and the differential influence of vertical relationships. PMID- 22322308 TI - ESUR prostate MR guidelines 2012. AB - The aim was to develop clinical guidelines for multi-parametric MRI of the prostate by a group of prostate MRI experts from the European Society of Urogenital Radiology (ESUR), based on literature evidence and consensus expert opinion. True evidence-based guidelines could not be formulated, but a compromise, reflected by "minimal" and "optimal" requirements has been made. The scope of these ESUR guidelines is to promulgate high quality MRI in acquisition and evaluation with the correct indications for prostate cancer across the whole of Europe and eventually outside Europe. The guidelines for the optimal technique and three protocols for "detection", "staging" and "node and bone" are presented. The use of endorectal coil vs. pelvic phased array coil and 1.5 vs. 3 T is discussed. Clinical indications and a PI-RADS classification for structured reporting are presented. KEY POINTS: This report provides guidelines for magnetic resonance imaging (MRI) in prostate cancer. Clinical indications, and minimal and optimal imaging acquisition protocols are provided. A structured reporting system (PI-RADS) is described. PMID- 22322309 TI - Cross-sectional area of the labrum: role in the diagnosis of anterior acetabular labral tears. AB - OBJECTIVE: To investigate the utility of ultrasound cross-sectional area (CSA) measurements for diagnosing acetabular labral (AL) tears. METHODS: The study included qualitative/quantitative ultrasound examinations of 55 hips in 52 patients with a presumed diagnosis of AL tear and 56 hips in 28 healthy volunteers. MR arthrography examinations were available only for the patients and were reviewed for the presence of AL thickening and tear. RESULTS: The CSA of the anterior labrum was significantly larger in patients with an AL tear on MR arthrography than those in healthy volunteers (P < 0.01). The CSA cut-off value in determining labral thickening that maximises accuracy was 34.7 mm(2), and sensitivity, specificity and accuracy were 86.7%, 74.1% and 77.5%. Direct signs of AL tear on ultrasound had sensitivity, specificity and accuracy of 34.9%, 91.7% and 47.3%. The CSA cut-off value that maximises the accuracy of the AL tear was 40.6 mm(2), and sensitivity, specificity and accuracy were 58.1%, 91.2% and 78.4%. CONCLUSIONS: Ultrasound detects the thickened labrum frequently observed in MR arthrography studies, especially in patients with dysplastic hips. Although specificity of the method of detecting AL tears is high, sensitivity is low, with an overlap between subjects with AL tear and controls. KEY POINTS: * Labral degeneration is frequent in dysplastic hips * Thickened labra are frequently observed on MR arthrograms * Labral thickening can be depicted by quantitative ultrasound measurements * The sensitivity is low with overlap between subjects with AL tear and controls. PMID- 22322310 TI - Quantitative evaluation of contrast-enhanced ultrasound after intravenous administration of a microbubble contrast agent for differentiation of benign and malignant thyroid nodules: assessment of diagnostic accuracy. AB - OBJECTIVES: To investigate the diagnostic accuracy, through quantitative analysis, of contrast-enhanced ultrasound (CEUS), using a microbubble contrast agent, in the differentiation of thyroid nodules. METHODS: This prospective study enrolled 46 patients with solitary, scintigraphically non-functional thyroid nodules. These patients were scheduled for surgery and underwent preoperative CEUS with pulse-inversion harmonic imaging after intravenous microbubble contrast medium administration. Using histology as a standard of reference, time-intensity curves of benign and malignant nodules were compared by means of peak enhancement and wash-out enhancement relative to the baseline intensity using a mixed model ANOVA. ROC analysis was performed to assess the diagnostic accuracy in the differentiation of benign and malignant nodules on CEUS. RESULTS: The complete CEUS data of 42 patients (31/42 [73.8%] benign and 11/42 [26.2%] malignant nodules) revealed a significant difference (P < 0.001) in enhancement between benign and malignant nodules. Furthermore, based on ROC analysis, CEUS demonstrated sensitivity of 76.9%, specificity of 84.8% and accuracy of 82.6%. CONCLUSIONS: Quantitative analysis of CEUS using a microbubble contrast agent allows the differentiation of benign and malignant thyroid nodules and may potentially serve, in addition to grey-scale and Doppler ultrasound, as an adjunctive tool in the assessment of patients with thyroid nodules. KEY POINTS: * Contrast-enhanced ultrasound (CEUS) helps differentiate between benign and malignant thyroid nodules. * Quantitative CEUS analysis yields sensitivity of 76.9% and specificity of 84.8%. * CEUS may be a potentially useful adjunct in assessing thyroid nodules. PMID- 22322311 TI - Predicting stroke evolution: comparison of susceptibility-weighted MR imaging with MR perfusion. AB - OBJECTIVES: To investigate the ability of susceptibility-weighted imaging (SWI) to predict stroke evolution in comparison with perfusion-weighted imaging (PWI). METHODS: In a retrospective analysis of 15 patients with non-lacunar ischaemic stroke studied no later than 24 h after symptom onset, we used the Alberta Stroke Program Early CT Score (ASPECTS) to compare lesions on initial diffusion-weighted images (DWI), SWI, PWI and follow-up studies obtained at least 5 days after symptom onset. The National Institutes of Health Stroke Scale scores at entry and stroke risk factors were documented. The clinical-DWI, SWI-DWI and PWI-DWI mismatches were calculated. RESULTS: SWI-DWI and mean transit time (MTT)-DWI mismatches were significantly associated with higher incidence of infarct growth (P = 0.007 and 0.028) and had similar ability to predict stroke evolution (P = 1.0). ASPECTS values on initial DWI, SWI and PWI were significantly correlated with those on follow-up studies (P <= 0.026) but not associated with infarct growth. The SWI ASPECTS values were best correlated with MTT ones (rho = 0.8, P < 0.001). CONCLUSIONS: SWI is an alternative to PWI to assess penumbra and predict stroke evolution. Further prospective studies are needed to evaluate the role of SWI in guiding thrombolytic therapy. Key Points * SWI can provide perfusion information comparable to MTT * SWI-DWI mismatch can indicate ischaemic penumbra * SWI-DWI mismatch can be a predictor for stroke evolution. PMID- 22322312 TI - MRI of the temporo-mandibular joint: which sequence is best suited to assess the cortical bone of the mandibular condyle? A cadaveric study using micro-CT as the standard of reference. AB - OBJECTIVE: To determine the best suited sagittal MRI sequence out of a standard temporo-mandibular joint (TMJ) imaging protocol for the assessment of the cortical bone of the mandibular condyles of cadaveric specimens using micro-CT as the standard of reference. METHODS: Sixteen TMJs in 8 human cadaveric heads (mean age, 81 years) were examined by MRI. Upon all sagittal sequences, two observers measured the cortical bone thickness (CBT) of the anterior, superior and posterior portions of the mandibular condyles (i.e. objective analysis), and assessed for the presence of cortical bone thinning, erosions or surface irregularities as well as subcortical bone cysts and anterior osteophytes (i.e. subjective analysis). Micro-CT of the condyles was performed to serve as the standard of reference for statistical analysis. RESULTS: Inter-observer agreements for objective (r = 0.83-0.99, P < 0.01) and subjective (kappa = 0.67 0.88) analyses were very good. Mean CBT measurements were most accurate, and cortical bone thinning, erosions, surface irregularities and subcortical bone cysts were best depicted on the 3D fast spoiled gradient echo recalled sequence (3D FSPGR). CONCLUSION: The most reliable MRI sequence to assess the cortical bone of the mandibular condyles on sagittal imaging planes is the 3D FSPGR sequence. KEY POINTS: MRI may be used to assess the cortical bone of the TMJ. * Depiction of cortical bone is best on 3D FSPGR sequences. * MRI can assess treatment response in patients with TMJ abnormalities. PMID- 22322313 TI - Expression of a humanized single-chain variable fragment antibody targeting chronic myeloid leukemia cells in Escherichia coli and its characterization. AB - Chronic myeloid leukemia (CML) is a malignant blood disease originating from hematopoietic stem cells. Drug resistance and tumor recurrence have become major problems for the treatment of this disease. Therefore, new therapeutic methods need to be developed. Antigens expressed on the surface of cancer cells are potential targets for antibody-mediated drug delivery. In our study, an anti-CML cell single-chain variable fragment (scFv) antibody has been produced and characterized because it is the first step towards the construction of a novel cancer-targeted agent for cancer diagnosis and treatment. Here, a 46 kDa antibody derivative was produced by genetic fusion of a humanized scFv antibody against a CML cell surface antigen with the 6xHis-tag, which can specifically bind to CML cells. The recombinant scFv against CML cells was expressed as a fusion protein containing the 6xHis-tag at its N-termini, and purified by Ni2+-NTA column chromatography. The recombinant scFv, which was soluble, was expressed and produced in bacteria, and was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and western blot assays. Finally, its cell-binding activity and immunoactivity were demonstrated by enzyme-linked immunosorbent assay (ELISA). Furthermore, flow cytometry analysis demonstrated that this scFv specifically targeted CML cells expressing the associated antigen (47.9 and 34.4%) other than non-expressing tumor cells (1.25%) in vitro. The results presented in this study illustrate that the humanized anti-CML cell scFv antibody may function as a novel therapeutic tool for CML. PMID- 22322314 TI - Effects of the flavonoid hesperidin in cerebral cortical progenitors in vitro: indirect action through astrocytes. AB - Flavonoids are polyphenolic compounds that are integral components of the human diet, universally present as constituents of fruits and vegetables as well as plant-derived foods and beverages such as oil, tea, and red wine. The biological activities of flavonoids cover a very broad spectrum, from anticancer and antibacterial activities to inhibition of bone reabsorption and modulation of inflammatory response. Although emerging evidence has suggested that flavonoids might have an impact on brain pathology and aging, their role as a mediator in interactions between neurons and glial cells has been poorly explored. In the present work, we have performed a screening of flavonoid actions by analyzing the effects of hesperidin, quercetin and rutin on murine cerebral cortex astrocytes and neural progenitors. Treatment of astrocytes with flavonoids did not interfere with cell viability and proliferation. However a culture of neural progenitors with conditioned medium from hesperidin treated-astrocyte (H-CM) yielded produced a 41% and 25% increase in the number of neural progenitors and post-mitotic neurons, respectively. The H-CM effect was mainly due to modulation of neuronal progenitor survival. Pools of astrocyte and oligodendrocyte progenitors were not affected by H-CM (hesperidin), Q-CM (quercetin) and R-CM (rutin). Q-CM and R-CM did not increase neuronal population. These results suggest that H-CM might be composed by a new factor that could modulate neuroglial interactions during central nervous system development and opens the possibility for using flavonoids as new therapeutic strategies for neurodegenerative diseases. PMID- 22322315 TI - Validation of evacuated canisters for sampling volatile organic compounds in healthcare settings. AB - Healthcare settings present a challenging environment for assessing low-level concentrations of specific volatile organic compounds (VOCs) in the presence of high background concentrations of alcohol from the use of hand sanitizers and surface disinfectants. The purposes of this laboratory-based project were to develop and validate a sampling and analysis methodology for quantifying low level VOC concentrations as well as high-level alcohol concentrations found together in healthcare settings. Sampling was conducted using evacuated canisters lined with fused silica. Gas chromatography/mass spectrometry analysis was performed using preconcentration (for ppb levels) and loop injection (for ppm levels). For a select list of 14 VOCs, bias, precision, and accuracy of both the preconcentration and loop injection methods were evaluated, as was analyte stability in evacuated canisters over 30 days. Using the preconcentration (ppb level) method, all validation criteria were met for 13 of the 14 target analytes ethanol, acetone, methylene chloride, hexane, chloroform, benzene, methyl methacrylate, toluene, ethylbenzene, m,p-xylene, o-xylene, alpha-pinene, and limonene. Using the loop injection (ppm-level) method, all validation criteria were met for each analyte. At ppm levels, alpha-pinene and limonene remained stable over 21 days, while the rest of the analytes were stable for 30 days. All analytes remained stable over 30 days at ppb levels. This sampling and analysis approach is a viable (i.e., accurate and stable) methodology that will enable development of VOC profiles for mixed exposures experienced by healthcare workers. PMID- 22322316 TI - A MRI-compatible system for whisker stimulation. AB - We describe here a system for whisker stimulation designed for functional studies in high-field magnetic resonance imaging (MRI) environments. This system, which incorporates real-time optical monitoring of the vibration stimulus, can generate well-controlled and reproducible whisker deflections with amplitudes up to 2mm and frequencies up to 75 Hz, suitable for functional magnetic resonance imaging (fMRI) studies of animals. Whiskers on either or both sides of the head can be stimulated selectively during fMRI experiments without removing the subject from the magnet. With a user-friendly graphical interface of a computer, a user can conveniently control both the whisker vibration and gating of the MR imager, and synchronize the stimulation with the fMRI acquisition to ensure precise timing of the stimulus presentation. This whisker stimulation system should facilitate a wide variety of fMRI investigations of the neural systems mediating sensory information from the whiskers. PMID- 22322318 TI - Quieting the inflammasome. PMID- 22322317 TI - Selection of regulatory T cells in the thymus. AB - The generation of regulatory T (T(Reg)) cells in the thymus is crucial for immune homeostasis and self-tolerance. Recent discoveries have revealed the cellular and molecular mechanisms that govern the differentiation of a subset of developing thymocytes into natural T(Reg) cells. Several models, centred on the self reactivity of the T cell receptor (TCR), have been proposed to explain the generation of a T(Reg) cell population that is cognizant of self. Several molecular pathways link TCR and cytokine signalling with the expression of the T(Reg) cell-associated transcription factor forkhead box P3 (FOXP3). Moreover, interplay between thymocytes and thymic antigen-presenting cells is also involved in T(Reg) cell generation. PMID- 22322319 TI - Maturation and function of NK cells. PMID- 22322320 TI - Prognostic significance of p16 in locoregionally advanced head and neck cancer treated with concurrent 5-fluorouracil, hydroxyurea, cetuximab and intensity modulated radiation therapy. AB - A phase II trial was conducted to evaluate the tolerability and efficacy of incorporating cetuximab and simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) into a well-described 5-fluorouracil (5-FU) and hydroxyurea (HU)-based chemoradiation regimen. Patients with stage IVa-IVb or high-risk stage III squamous cell carcinomas were enrolled. Prior organ conserving surgery or induction chemotherapy was allowed. IMRT was administered in 1.5 Gy fractions twice daily on days 1-5 of weeks 1, 3, 5, 7+/-9 for a total dose of 60-73.5 Gy. Concurrent systemic therapy consisted of 5-FU (600 mg/m2), HU (500 mg BID) and cetuximab (250 mg/m2). p16INK4A expression was assessed by immunohistochemistry. From January 2007 to January 2010, 65 patients (61 with stage IV disease; 31 with oropharyngeal primaries) were enrolled. At a median follow-up of 28 months, 2-year locoregional control, distant control, progression free survival, event-free survival and overall survival were 79, 83, 72, 63 and 80%, respectively. In 48 patients with available pre-treatment tissue, p16 overexpression was associated with significantly increased distant control (p=0.03), progression-free survival (p=0.02), event-free survival (p=0.007) and overall survival (p=0.03). The most common grade 3-4 toxicities were mucositis (46%), leukopenia (18%), anemia (18%) and dermatitis (17%). Concurrent 5-FU, HU, cetuximab and SIB-IMRT is a highly active regimen, particularly in patients with p16-positive disease. PMID- 22322321 TI - Novel four-way Ph translocation t(9;22;7;1)(q34;q11;q22;p13) in a chronic myeloid leukemia patient receiving tyrosine kinase inhibitor therapy. AB - The occurrence of a four-way Philadelphia chromosome translocation is a very rare event in myeloid malignancies, and the phenotypic consequences of such rearrangements remain to be investigated. We describe a case of a chronic myeloid leukemia (CML) patient with a complex four-way t(9;22;7,1) translocation who received multiple tyrosine kinase inhibitor therapy. As evaluation of prognostic features in a limited number of patients with four-way Philadelphia rearrangements at present yields controversial results, our case may add further information on the prognostic impact of such abnormalities in CML patients receiving tyrosine kinase inhibitor therapy, and may help delineate a sub-group of patients requiring different therapeutic approaches. PMID- 22322322 TI - Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features. AB - Malignant epithelial tumors (carcinomas) are the most common ovarian cancers and also the most lethal gynecological malignancies. Based on histopathology and molecular genetic alterations, ovarian carcinomas are divided into five main types (high-grade serous (70%), endometrioid (10%), clear cell (10%), mucinous (3%), and low-grade serous carcinomas (<5%)) that account for over 95% of cases. These types are essentially distinct diseases, as indicated by differences in epidemiological and genetic risk factors, precursor lesions, patterns of spread, and molecular events during oncogenesis, response to chemotherapy, and prognosis. For a successful specific treatment, reproducible histopathological diagnosis of the tumor cell type is critical. The five tumor types are morphologically diverse and resemble carcinomas of the uterus. Actually, recent investigations have demonstrated that a significant number of cancers, traditionally thought to be primary ovarian tumors (particularly serous, endometrioid, and clear cell carcinomas), originate in the fallopian tube and the endometrium and involve the ovary secondarily. This review summarizes recent advances in the molecular pathology which have greatly improved our understanding of the biology of ovarian carcinoma and are also relevant to patient management. PMID- 22322323 TI - Practical biocatalytic desymmetrization of meso-N-heterocyclic dicarboxamides and their application in the construction of aza-sugar containing nucleoside analogs. AB - Amidase-catalyzed desymmetrization of meso-N-heterocyclic dicarboxamides under very mild conditions provided a highly efficient and practical method for the preparation of enantiomerically pure carbamoyl-substituted heterocyclic amino acids that were unique and versatile platforms for the construction of both antipodes of aza-sugar containing nucleoside analogs. PMID- 22322324 TI - Depressive and cardiovascular disease comorbidity in a rat model of social stress: a putative role for corticotropin-releasing factor. AB - RATIONALE: Depression is associated with medical comorbidities, particularly cardiovascular disease. However, mechanisms linking depression and cardiovascular disease remain unclear. OBJECTIVES: This study investigated whether the rat resident-intruder model of social stress would elicit behavioral dysfunctions and autonomic changes characteristic of psychiatric/cardiovascular comorbidity. Furthermore, the efficacy of the corticotropin-releasing factor-1 (CRF(1)) receptor antagonist, NBI-30775 (NBI), or the tricyclic antidepressant, desipramine (DMI), to prevent social stress-induced behavioral, neuroendocrine, and cardiovascular changes were evaluated. METHODS: Adult male rats were exposed to resident-intruder stress (seven consecutive days) and systemically administered NBI (10 mg/kg/7 days), DMI (10 mg/kg/14 days), or vehicle. The efficacy of NBI and DMI to alter the behavioral and neuroendocrine responses to social stress was assessed. Furthermore, their effects on stress-induced forced swim behavior (FST), bladder and adrenal weight, and heart rate variability (HRV) were examined. RESULTS: NBI, but not DMI, increased time spent in an upright, defensive posture and the latency to submit to the resident. Additionally, only NBI reduced social stress-induced adrenocorticotropic hormone and corticosterone release. Social stress increased FST immobility, caused bladder and adrenal hypertrophy, and decreased HRV. Both NBI and DMI blocked stress-induced increases in immobility during the FST. However, only NBI inhibited social stress-induced adrenal and bladder hypertrophy and decreases in heart rate variability. CONCLUSIONS: Rat resident-intruder stress paradigm models aspects of psychiatric/medical comorbidity. Furthermore, the CRF system may contribute to both the behavioral response during social stress and its behavioral and autonomic consequences, offering insight into potential therapy to treat these comorbid conditions. PMID- 22322325 TI - The evolution of a community-based telepsychiatry program in rural Alabama: lessons learned-a brief report. AB - The purpose of this paper is to describe the partnership between a community based rural mental health clinic and an academic health center to provide telepsychiatry services in rural Alabama. The partnership was developed to meet the needs of a clinic that serves an underserved rural population with limited psychiatric services. This paper offers valuable lessons learned for mental health practitioners who may be considering the benefits and challenges of forming community-based partnerships in use of telepsychiatry to build capacity to deliver clinical mental health services to rural mental health shortage areas. PMID- 22322326 TI - How to perform ventricular tachycardia ablation with a percutaneous left ventricular assist device. PMID- 22322327 TI - Potential depot medroxyprogesterone acetate-triggered torsades de pointes in a case of congenital type 2 long QT syndrome. PMID- 22322328 TI - Value of right ventricular mapping in patients with postinfarction ventricular tachycardia. AB - BACKGROUND: Postinfarction ventricular tachycardia (VT) typically involves the left ventricular endocardium. Right ventricular involvement in the arrhythmogenic substrate of postinfarction VT is considered unusual. OBJECTIVE: To assess the role of right ventricular mapping and ablation in patients with prior septal myocardial infarction. METHODS: From among 37 consecutive patients with recurrent postinfarction VT, 18 patients with evidence of left ventricular septal involvement of myocardial infarction were identified; these patients were the subjects of this report. In these 18 patients, 166 VTs (cycle length 372 +/- 117 ms) were induced. Right ventricular voltage mapping was performed in all 18 patients with left ventricular septal myocardial infarction. RESULTS: Right ventricular voltage mapping showed areas of low voltage in 11 patients; pace mapping from these areas revealed matching pace maps for 17 VTs, and radiofrequency ablation from the right ventricular endocardium but not the left ventricular endocardium eliminated 14 of 17 VTs. VTs with critical components in the right ventricle had a left bundle branch block morphology that had similar characteristics as left bundle branch block VTs with critical areas involving the left ventricular septum. Patients with right ventricular VT breakthrough sites had a lower ejection fraction than did patients without VT breaking out on the right ventricular septum (18% +/- 5% vs 33% +/- 15%; P = .01). CONCLUSIONS: Right ventricular mapping and ablation may be necessary in order to eliminate all inducible VTs in patients with postinfarction VT. More than half the patients with septal myocardial infarction have right ventricular septal areas that are critical for postinfarction VT and that cannot be eliminated by left ventricular ablation alone. PMID- 22322329 TI - Pulmonary vein remapping: adequate shortcut or cut too short? PMID- 22322330 TI - Modeling of InAs-InSb nanowires grown by Au-assisted chemical beam epitaxy. AB - Interesting phenomena during the Au-assisted chemical beam epitaxy of InAs-InSb nanowire heterostructures have been observed and interpreted within the framework of a theoretical model. An unusual, non-monotonous diameter dependence of the InSb nanowire growth rate is demonstrated experimentally within a range of deposition conditions. Such a behavior is explained by competition between the Gibbs-Thomson effect and different diffusion-induced material fluxes. Theoretical fits to the experimental data obtained at different flux pressures of In and Sb precursors allow us to deduce some important kinetic coefficients. Furthermore, we discuss why the InAs nanowire stem forms in the wurtzite phase while the upper InSb part has a pure zinc blende crystal structure. It is hypothesized that the 30 degrees angular rotation of nanowire when passing from InAs to the InSb part is driven by the lowest surface energy of (1100) wurtzite and (110) zinc blende facets. PMID- 22322331 TI - The effect of religious service attendance on race differences in depression: findings from the EHDIC-SWB study. AB - In the EHDIC-SWB study, African-Americans are less likely to have depression than non-Hispanic whites. Religious service attendance is one possible explanation because studies have shown an inverse relationship between religious service attendance and depression. We examined the relationship between race, religious service attendance, and depression in 835 African-American and 573 non-Hispanic white adults aged 18 and older in the Exploring Health Disparities in Integrated Communities-Southwest Baltimore (EHDIC-SWB) study. Religious service attendance was measured according to participants' response to "how often do you attend religious services?" Depression was measured using the Patient Health Questionnaire. African-Americans attended religious services more frequently than non-Hispanic whites, and had a lower percentage of depression (10.1% vs. 15.4%; p value <0.05). After adjusting for the demographic variables and health-related characteristics, African-Americans displayed lower odds of having depression (OR = 0.68, 95% CI: 0.47-0.97) compared to non-Hispanic whites. However, when including religious service attendance in the model, we found race differences in depression (OR = 0.76, 95% CI: 0.52-1.11) were no longer significant. We concluded that among individuals living in a low-income, integrated urban environment, race disparities in depression were eliminated after accounting for race differences in religious service attendance. This suggests religious service attendance may serve as a protective factor against depression for African Americans. PMID- 22322332 TI - Significance of increasing poverty levels for determining late-stage breast cancer diagnosis in 1990 and 2000. AB - We examine the association between late-stage breast cancer diagnosis and residential poverty in Detroit, Atlanta, and San Francisco in 1990 and 2000. We tested whether residence in census tracts with increasing levels of poverty were associated with increased odds of a late-stage diagnosis in 1990 and 2000 and found that it was. To test this, we linked breast cancer cases from the Surveillance, Epidemiology, and End Results cancer registries with poverty data from the census. Tracts were grouped into low, moderate, and high poverty based on the percentage of households reporting income below the poverty level. While late-stage breast cancer rates and the number of women living in high and moderate-poverty areas declined absolutely between 1990 and 2000, estimates from our combined three-city model showed that odds of a late-stage diagnosis remained stubbornly elevated in increasingly poor areas in both years. Non-Hispanic black women faced higher odds of a late-stage diagnosis relative to non-Hispanic white women in both years. In separate regressions for each city, the odds ratios affirm that combining data across cities may be misleading. In 1990 and 2000, only women living in moderately poor neighborhoods of San Francisco faced elevated odds, while in Detroit women in both moderate- and high-poverty areas faced increased likelihood of late-stage diagnosis. In Atlanta, none of the poverty measures were significant in 1990 or 2000. In our test of physician supply on stage, an increase in the number of neighborhood primary care doctor's offices was associated with decreased odds of a late-stage diagnosis only for Detroit residents and for non-Hispanic whites in the three-city model. PMID- 22322333 TI - [Analyses of pesticides in drinking water from small-scale water supplies in Schleswig-Holstein, Germany]. AB - In rural areas of Schleswig-Holstein, Germany, drinking water for about 37 000 people is provided by approximately 10 000 small-scale water supplies. For those wells data on pesticides in the drinking water are rare. In this study 100 small scale water supplies, mainly situated in areas with intensive agriculture, fruit growing or tree-nursery, were selected and the drinking water was analysed for pesticides. In 68 samples at least one agent or metabolite was detectable, 38 samples showed multiple contaminations. The metabolites dimethylsulfamide and chloridazone-desphenyl were found in nearly 40% of the wells in concentrations up to 42 ug/L. Bentazone was the most frequently detected biocidal agent. These data show that pesticides in drinking water from small-scale supplies are a notable issue in preventive public health. PMID- 22322334 TI - [Frequency of pressure ulcers in german hospitals]. AB - The prevalence and incidence of pressure ulcers are increasingly used to assess the quality of care delivered by health systems and facilities and the effectiveness of the pressure ulcer prevention initiatives in place. Available results about pressure ulcer prevalence and incidence in German hospitals are contradictory. The comparison of 3 multicentre nationwide studies is proposed to provide a more accurate estimation of the pressure ulcer frequency. Pressure ulcer prevalence was compared by data provided by the Charite with data of the software-based data collection packet "Kinexus". Additionally, data on pressure ulcer incidence of Kinexus were compared with the results of the incidence data of the "Generalindikator Dekubitusprophylaxe" of the German Society of Quality Assurance (BQS, now AQUA Institute). Data from 2007 and 2008 and patients 75 years and older were considered. For the calculation of the outcome "pressure ulcer" recommendations of the EPUAP and the NPUAP were followed. As category I (non-bleaching erythema) pressure ulcers are difficult to diagnose, all proportions were calculated including and excluding category I. All 3 samples were comparable regarding the mean age of 81 years. Pressure ulcer prevalence categories I-IV (II-IV) of the Kinexus study was 11.8% (6.1%) and of the Charite study it was 11.0% (5.5%). Regarding pressure ulcer incidence, the rate that was calculated by the BQS categories I-IV (II-IV) was 1.3% (0.8%), in comparison to the incidence rate of Kinexus which was 6.7% (3.9%). There were no statistically significant differences between the 2 prevalence measurements but the odds-ratio of the Kinexus incidence in comparison to the BQS incidence was more than 4 times higher (p<0.001). Results of the Kinexus study are more comparable to incidence figures of international studies on pressure ulcer incidence. The results of this secondary data analysis indicate that published incidence figures by the BQS (now AQUA Institute) might be underestimated. Since this measurement is expensive and burdensome, this mandatory procedure is questionable. PMID- 22322335 TI - [Quality of life in the focus of quality audits in long-term care]. AB - Quality of life - an important outcome factor of long-term care - development and psychometric testing of an audit instrument, the Quality of Life Index, (QoL index"), to assess the consideration for individual quality of life aspects during the care process in long-term care settings is evaluated - even for clients with limited communication skills.A stratified random sample of n=209 residents was drawn out of the population of N=1 128 residents of 8 nursing homes and their individual QoL-aspects were assessed with SEIQoL-DW or in difficult communication situations with "LQ-Index-Informationssammlung". The LQ-Index's new items were validated via a parallel testing with the reference instrument SEIQoL DW, the split half-reliability, the interrater reliability (Kappa) and a structured expert review according to the cognitive interview technique.All 209 participants were assessed via LQ-Index. The SEIQoL-Interview was completed and estimated valid by 18 (8.61%) residents. The psychometric testing results and the expert review indicate high feasibility, good reliability, validity and objectivity of the instrument "LQ-Index".As a result of this study a feasible and valid instrument is now available to assess the consideration for individual quality of life aspects during the care process in long-term care settings - even for clients with limited communication skills. PMID- 22322336 TI - Spirituality and support: a descriptive analysis of online social support for depression. AB - This study examined supportive messages in spiritual and non-spiritual online support groups for depression. Both social support and religiosity have been associated with reduced depressive symptomology. Proportions of three types of support (i.e., informational, emotional, and network) were considered; messages were further delineated as being either religious or non-religious in nature. Messages (N=2,674) from two Christian and two unaffiliated online groups were analyzed. Results indicated that Christian groups communicated more informational support and General groups communicated more network support. Christian groups communicated more religious messages. This and future research is valuable to practitioners and clergy aiding depressed individuals and to the literature on social support and religion. PMID- 22322337 TI - The current challenges for vaccine development. AB - Vaccine development has played a hugely important role in combating infectious disease. Despite this success, there is still a great need for new vaccines and these are emerging far more slowly than we would wish. Despite the massive expansion in understanding of immune responses to infection, research is often hindered by a lack of understanding of the immune responses required specifically for protection, or by a lack of approved adjuvants and delivery systems to induce the required responses. In addition, the financial commitment required to license new vaccines is significant, and the more lucrative markets are often not those with the greatest need. In this review, we discuss many of the hurdles that new vaccines must overcome in order to reduce morbidity and mortality, and some of the initiatives that are being attempted to supply new vaccines to those that need them most. PMID- 22322338 TI - Characterization of a Staphylococcus aureus USA300 protein signature using matrix assisted laser desorption/ionization time-of-flight mass spectrometry. AB - Staphylococcus aureus strain type USA300 is an important human pathogen. Matrix assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry has been used successfully for rapid identification of S. aureus at the genus and species levels. Here, it was hypothesized that MALDI-TOF could be used to identify USA300 organisms at the strain level. A genetic algorithm model using ClinProTools software (Bruker Daltonics) was built using 47 isolates of USA300 S. aureus and 77 non-USA300 S. aureus isolates. Three mass/charge peaks (5932, 6423 and 6592) were found to be discriminators between the groups of isolates. The model was validated using 224 test isolates: 197 of 224 test isolates were correctly classified as 'USA300 family' or 'non-USA300'. The sensitivity of the model was 0.87, with a specificity of 0.89, positive likelihood ratio of 8.19 and negative likelihood ratio of 0.15. The three-peak intensity MALDI-TOF model designed and tested in the current study can be used to rapidly identify USA300 family S. aureus isolates with reasonable sensitivity and specificity. PMID- 22322339 TI - Distribution and phenotypic and genotypic detection of a metallo-beta-lactamase, CphA, among bacteraemic Aeromonas isolates. AB - The objectives of the study were to investigate the distribution of cphA-related genes (cphA) encoding a CphA metallo-beta-lactamase (MBL) among 51 consecutive Aeromonas blood isolates and to compare different phenotypic methods for detecting CphA. The presence of cphA was detected by PCR. Four phenotypic methods, the imipenem-EDTA combined disc test, imipenem-EDTA MBL Etest, agar dilution test and modified Hodge test (MHT), were used to detect imipenem susceptibility and MBL production. The results showed that 35 (69%) blood isolates had cphA. All (100%) of 16 Aeromonas aquariorum isolates and 12 Aeromonas veronii isolates, and 4 (80%) of 5 Aeromonas hydrophila isolates, carried cphA, but none of 15 Aeromonas caviae isolates did. With the standard inocula, irrespective of the presence or absence of cphA, all but one (50, 98%) isolates were susceptible to imipenem tested by disc diffusion, Etest and agar dilution (10(4) c.f.u. spot inocula), and did not exhibit MBL production by the imipenem-EDTA combined disc test and MBL Etest. By the agar dilution test using large inocula (10(7) c.f.u.), 34 (97%) of 35 cphA(+) isolates had imipenem MICs of >=16 ug ml(-1), higher than the susceptible breakpoint (4 ug ml(-1)), and demonstrated positive results for the MHT, while one cphA(+) and all 17 cphA(-) isolates had imipenem MICs of <=4 ug ml(-1). In conclusion, the distribution of cphA among aeromonads is species-specific, found in A. aquariorum, A. veronii and A. hydrophila, and the MHT may be a phenotypic screening test for CphA production. PMID- 22322340 TI - Utility of real-time amplification of selected 16S rRNA gene sequences as a tool for detection and identification of microbial signatures directly from clinical samples. AB - The potential of incorporating a real-time PCR for amplification and detection of 16S rRNA gene signatures directly from clinical samples was assessed as a tool for diagnostics. Universal PCR primers spanning short variable regions (~500 bp) were optimized for real-time PCR and tested in comparison with a longer fragment (~1400 bp) generated from block-based amplification. Real-time PCR had improved sensitivity of detection (8% increase), decreased amplification time and simplified downstream processing. The real-time PCR primers also offered an improvement in detection of bacteria from samples that demonstrated inhibition with the block-based primers and in the resolution of mixed-sequence traces. In addition to testing primer sensitivity, the effect of amplifying and sequencing two different variable regions of the 16S rRNA gene on organism identification was compared. By amplifying and sequencing a shorter variable region, the number of species that were identified to the species level was reduced by 18%. PMID- 22322341 TI - Exposure assessment of tetrafluoroethylene and ammonium perfluorooctanoate 1951 2002. AB - OBJECTIVES: To develop a method to reconstruct exposure to tetrafluoroethylene (TFE) and ammonium perfluorooctanoate (APFO) in plants producing polytetrafluoroethylene (PTFE) in the absence of suitable objective measurements. These data were used to inform an epidemiological study being carried out to investigate possible risks in workers employed in the manufacture of PTFE and to study trends in exposure over time. METHODS: For each plant, detailed descriptions of all occupational titles, including tasks and changes over time, were obtained during semi-structured interviews with key plant personnel. A semi quantitative assessment method was used to assess inhalation exposure to TFE and inhalation plus dermal exposure to APFO. Temporal trends in exposure to TFE and APFO were investigated. RESULTS: In each plant the highest exposures for both TFE and APFO occurred in the polymerisation area. Due to the introduction of control measures, increasing process automation and other improvements, exposures generally decreased over time. In the polymerisation area, the annual decline in exposure to TFE varied by plant from 3.8 to 5.7% and for APFO from 2.2 to 5.5%. CONCLUSIONS: A simple method for assessing exposure was developed which used detailed process information and job descriptions to estimate average annual TFE and APFO exposure on an arbitrary semi-quantitative scale. These semi quantitative estimates are sufficient to identify relative differences in exposure for the epidemiological study and should good data become available, they could be used to provide quantitative estimates for all plants across the whole period of operation. PMID- 22322342 TI - Comparison between heparin-conjugated fibrin and collagen sponge as bone morphogenetic protein-2 carriers for bone regeneration. AB - Bone morphogenetic protein-2 (BMP-2) is used to promote bone regeneration. However, the bone regeneration ability of BMP-2 relies heavily on the delivery vehicle. Previously, we have developed heparin- conjugated fibrin (HCF), a vehicle for long-term delivery of BMP-2 and demonstrated that long-term delivery of BMP-2 enhanced its osteogenic efficacy as compared to short-term delivery at an equivalent dose. The aim of this study was to compare the bone-forming ability of the BMP-2 delivered by HCF to that delivered by clinically utilized BMP-2 delivery vehicle collagen sponge. An in vitro release profile of BMP-2 showed that HCF released 80% of the loaded BMP-2 within 20 days, whereas collagen sponge released the same amount within the first 6 days. Moreover, the BMP-2 released from the HCF showed significantly higher alkaline phosphatase activity than the BMP-2 released from collagen sponge at 2 weeks in vitro. Various doses of BMP-2 were delivered with HCF or collagen sponge to mouse calvarial defects. Eight weeks after the treatment, bone regeneration was evaluated by computed tomography, histology, and histomorphometric analysis. The dose of BMP-2 delivered by HCF to achieve 100% bone formation in the defects was less than half of the BMP-2 dose delivered by collagen sponge to achieve a similar level of bone formation. Additionally, bone regenerated by the HCF-BMP-2 had higher bone density than bone regenerated by the collagen sponge-BMP-2. These data demonstrate that HCF as a BMP-2 delivery vehicle exerts better osteogenic ability of BMP-2 than collagen sponge, a clinically utilized delivery vehicle. PMID- 22322343 TI - What proportion of lung cancer in never-smokers can be attributed to known risk factors? AB - Though tobacco smoking is the primary risk factor for lung cancer, a significant fraction of lung cancer deaths occur in lifetime nonsmokers. In this article, we calculate the burden of lung cancer in never-smokers attributable to previously identified risk factors in North America, Europe and China, using population based estimates of exposure prevalence and estimates of relative risk derived from recently published meta-analyses. Population attributable fractions (PAFs) for individual risk factors ranged from 0.40 to 19.93%. Because of differences in the prevalence of exposures, the PAFs associated with several of the risk factors varied greatly by geographical region. Exposure to the selected risk factors appeared to explain a much larger proportion of lung cancer cases in never smokers in China than in Europe and North America. Our results demonstrate the geographic variability of the epidemiology of lung cancer in never-smokers and highlight the need for further research in this area, particularly in Europe and North America. PMID- 22322344 TI - Fermentable carbohydrate alters hypothalamic neuronal activity and protects against the obesogenic environment. AB - Obesity has become a major global health problem. Recently, attention has focused on the benefits of fermentable carbohydrates on modulating metabolism. Here, we take a system approach to investigate the physiological effects of supplementation with oligofructose-enriched inulin (In). We hypothesize that supplementation with this fermentable carbohydrate will not only lead to changes in body weight and composition, but also to modulation in neuronal activation in the hypothalamus. Male C57BL/6 mice were maintained on a normal chow diet (control) or a high fat (HF) diet supplemented with either oligofructose-enriched In or corn starch (Cs) for 9 weeks. Compared to HF+Cs diet, In supplementation led to significant reduction in average daily weight gain (mean +/- s.e.m.: 0.19 +/- 0.01 g vs. 0.26 +/- 0.02 g, P < 0.01), total body adiposity (24.9 +/- 1.2% vs. 30.7 +/- 1.4%, P < 0.01), and lowered liver fat content (11.7 +/- 1.7% vs. 23.8 +/- 3.4%, P < 0.01). Significant changes were also observed in fecal bacterial distribution, with increases in both Bifidobacteria and Lactobacillius and a significant increase in short chain fatty acids (SCFA). Using manganese enhanced MRI (MEMRI), we observed a significant increase in neuronal activation within the arcuate nucleus (ARC) of animals that received In supplementation compared to those fed HF+Cs diet. In conclusion, we have demonstrated for the first time, in the same animal, a wide range of beneficial metabolic effects following supplementation of a HF diet with oligofructose-enriched In, as well as significant changes in hypothalamic neuronal activity. PMID- 22322345 TI - Comparison of the Microflex LT and Vitek MS systems for routine identification of bacteria by matrix-assisted laser desorption ionization-time of flight mass spectrometry. AB - This study compared the performance of three matrix-assisted laser desorption ionization-time of flight mass spectrometry systems: Microflex LT (Bruker Daltonics, Bremen, Germany), Vitek MS RUO (Axima Assurance-Saramis database; bioMerieux, Marcy l'Etoile, France), and Vitek MS IVD (bioMerieux). A total of 1,129 isolates, including 1,003 routine isolates, 73 anaerobes, and 53 bacterial enteropathogens, were tested on the Microflex LT and Axima Assurance devices. The spectra were analyzed using three databases: Biotyper (Bruker Daltonics), Saramis, and Vitek MS (bioMerieux). Among the routine isolates requiring identification to the species level (n = 986), 92.7% and 93.2% were correctly identified by the Biotyper and Vitek MS databases, respectively. The Vitek MS database is more specific for the identification of Streptococcus viridans. For the anaerobes, the Biotyper database often identified Fusobacterium isolates to only the genus level, which is of low clinical significance, whereas 20% of the Bacteroides species were not identified or were misidentified by the Vitek MS database. For the enteropathogens, the poor discrimination between Escherichia coli and Shigella explains the high proportion of unidentified organisms. In contrast to the Biotyper database, the Vitek MS database properly discriminated all of the Salmonella entrica serovar Typhi isolates (n = 5). The performance of the Saramis database was globally poorer. In conclusion, for routine procedures, the Microflex LT and Vitek-MS systems are equally good choices in terms of analytical efficiency. Other factors, including price, work flow, and lab activity, will affect the choice of a system. PMID- 22322346 TI - Development of mitochondrial loop-mediated isothermal amplification for detection of the small liver fluke Opisthorchis viverrini (Opisthorchiidae; Trematoda; Platyhelminthes). AB - Mitochondrial DNA sequences offer major advantages over the more usual nuclear targets for loop-mediated isothermal amplification approaches (mito-LAMP) because multiple copies occur in every cell. Four LAMP primers [F3, FIP(F1c+F2), BIP(B1c+B2), and B3] were designed based on the mitochondrial nad1 sequence of Opisthorchis viverrini and used for a highly specific assay (mito-OvLAMP) to distinguish DNA of O. viverrini from that of another opisthorchiid (Clonorchis sinensis) and other trematodes (Haplorchis pumilio, Haplorchis taichui, Fasciola hepatica, and Fasciola gigantica). Conventional PCR was applied using F3/B3 primer pairs to verify the specificity of the primers for O. viverrini DNA templates. All LAMP-positive samples could be detected with the naked eye in sunlight, by gel electrophoresis (stained with ethidium bromide), and by addition of SYBR green I to the product in sunlight or under UV light. Only DNA from O. viverrini yielded amplification products by LAMP (and by PCR verification), and the LAMP limit of detection was as little as 100 fg (10(-4) ng DNA), indicating that this assay is 10 to 100 times more sensitive than PCR. Field testing was done using representative egg and metacercarial samples collected from localities where the fluke is endemic. With the advantages of simplicity, rapidity, sensitivity, and cost effectiveness, mito-OvLAMP is a good tool for molecular detection and epidemiology studies in regions or countries where O. viverrini is endemic, which can lead to more effective control of opisthorchiasis and trematodiasis. PMID- 22322347 TI - Epidemiological significance of the domestic black pig (Sus scrofa) in maintenance of bovine tuberculosis in Sicily. AB - Bovine tuberculosis (bTB) is an emerging disease among wild animals in many parts of the world. Wildlife reservoir hosts may thus represent a potential source of infection for livestock and humans. We investigated the role played by the Sicilian black pig, an autochthonous free- or semi-free-ranging domestic pig breed, as a potential source of bTB infection in an area where bTB prevalence in cattle is high. We initially performed a preliminary field study to assess the occurrence of bTB in such animals. We sampled 119 pigs at abattoir and found 6.7% and 3.4% of them to be affected by gross tuberculous-like lesions (TBL) and Mycobacterium bovis culture positive, respectively. We then proceeded to investigate the dissemination and characteristics of lesions in a second field study performed on 100 animals sampled from infected herds. Here, tissues collected at the abattoir were examined macroscopically, microscopically, and by culture tests. Most pigs with TBL showed generalized lesions in both gross and histological examinations (53% and 65.5%, respectively). Head lymph nodes were the most frequently affected in both localized and generalized TB cases observed macroscopically and microscopically. M. bovis was the most frequently isolated etiologic agent. The molecular characterization of isolates from both field studies by spoligotyping and analysis of 12 mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) loci, followed by their comparison to isolates of cattle origin, suggested a potential transmission of mycobacteria from domestic animals to black pigs and vice versa. Our findings, along with ethological, ecological, and management considerations, suggest that the black pig might act as a bTB reservoir in the ecosystem under study. However, additional studies will be necessary to establish the true epidemiological significance of the Sicilian black pig. PMID- 22322348 TI - Diagnostic performance of a multiple real-time PCR assay in patients with suspected sepsis hospitalized in an internal medicine ward. AB - Early identification of causative pathogen in sepsis patients is pivotal to improve clinical outcome. SeptiFast (SF), a commercially available system for molecular diagnosis of sepsis based on PCR, has been mostly used in patients hospitalized in hematology and intensive care units. We evaluated the diagnostic accuracy and clinical usefulness of SF, compared to blood culture (BC), in 391 patients with suspected sepsis, hospitalized in a department of internal medicine. A causative pathogen was identified in 85 patients (22%). Sixty pathogens were detected by SF and 57 by BC. No significant differences were found between the two methods in the rates of pathogen detection (P = 0.74), even after excluding 9 pathogens which were isolated by BC and were not included in the SF master list (P = 0.096). The combination of SF and BC significantly improved the diagnostic yield in comparison to BC alone (P < 0.001). Compared to BC, SF showed a significantly lower contamination rate (0 versus 19 cases; P < 0.001) with a higher specificity for pathogen identification (1.00, 95% confidence interval [CI] of 0.99 to 1.00, versus 0.94, 95% CI of 0.90 to 0.96; P = 0.005) and a higher positive predictive value (1.00, 95% CI of 1.00 to 0.92%, versus 0.75, 95% CI of 0.63 to 0.83; P = 0.005). In the subgroup of patients (n = 191) who had been receiving antibiotic treatment for >=24 h, SF identified more pathogens (16 versus 6; P = 0.049) compared to BC. These results suggest that, in patients with suspected sepsis, hospitalized in an internal medicine ward, SF could be a highly valuable adjunct to conventional BC, particularly in patients under antibiotic treatment. PMID- 22322349 TI - Using nucleic acid microarrays to perform molecular epidemiology and detect novel beta-lactamases: a snapshot of extended-spectrum beta-lactamases throughout the world. AB - The worldwide dissemination of extended-spectrum-beta-lactamase (ESBL)- and carbapenemase-producing Enterobacteriaceae is a major concern in both hospital and community settings. Rapid identification of these resistant pathogens and the genetic determinants they possess is needed to assist in clinical practice and epidemiological studies. A collection of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus mirabilis isolates, including phenotypically ESBL positive (n = 1,093) and ESBL-negative isolates (n = 59), obtained in 2008-2009 from a longitudinal surveillance study (SMART) was examined using an in vitro nucleic acid-based microarray. This approach was used to detect and identify bla(ESBL) (bla(SHV), bla(TEM), and bla(CTX-M) genes of groups 1, 2, 9, and 8/25) and bla(KPC) genes and was combined with selective PCR amplification and DNA sequencing for complete characterization of the bla(ESBL) and bla(KPC) genes. Of the 1,093 phenotypically ESBL-positive isolates, 1,041 were identified as possessing at least one bla(ESBL) gene (95.2% concordance), and 59 phenotypically ESBL-negative isolates, used as negative controls, were negative. Several ESBL variants of bla(TEM) (n = 5), bla(SHV) (n = 11), bla(CTX-M) (n = 19), and bla(KPC) (n = 3) were detected. A new bla(SHV) variant, bla(SHV-129), and a new bla(KPC) variant, bla(KPC-11), were also identified. The most common bla genes found in this study were bla(CTX-M-15), bla(CTX-M-14), and bla(SHV-12). Using nucleic acid microarrays, we obtained a "molecular snapshot" of bla(ESBL) genes in a current global population; we report that CTX-M-15 is still the dominant ESBL and provide the first report of the new beta-lactamase variants bla(SHV-129) and bla(KPC-11). PMID- 22322350 TI - Purpureocillium lilacinum as a cause of cavitary pulmonary disease: a new clinical presentation and observations on atypical morphologic characteristics of the isolate. AB - The first case of cavitary pulmonary disease caused by Purpureocillium lilacinum is described. The isolate showed atypical microscopic characteristics similar to Acremonium and Fusarium spp., which necessitated molecular identification by sequencing of multiple conserved loci. The patient responded to voriconazole, reinforcing its therapeutic efficacy for P. lilacinum infections. PMID- 22322351 TI - Rapid detection of ampicillin resistance in Escherichia coli by quantitative mass spectrometry. AB - Early targeted antimicrobial therapy helps decrease costs and prevents the spread of antimicrobial resistance, including in Escherichia coli, the most frequent Gram-negative bacterium that causes sepsis. Therefore, rapid susceptibility testing represents the major prerequisite for knowledge-based successful antimicrobial treatment. To accelerate testing for antibiotic susceptibility, we have developed a new mass spectrometry-based assay for antibiotic susceptibility testing (MAAST). For proof of principle, we present an ampicillin susceptibility test for E. coli with a turnaround time of 90 min upon growth detection. PMID- 22322352 TI - Emergence of a mutL mutation causing multilocus sequence typing-pulsed-field gel electrophoresis discrepancy among Pseudomonas aeruginosa isolates from a cystic fibrosis patient. AB - A multilocus sequence type (MLST) shift (from ST242 to ST996) was detected in Pseudomonas aeruginosa isolates with a uniform pulsed-field gel electrophoresis (PFGE) pattern obtained from a chronically colonized patient. MLST mutational change involved the mutL gene with the consequent emergence of a hypermutable phenotype. This observation challenges the required neutrality of mutL as an appropriate marker in MLST and alerts researchers to the limitations of MLST-only based population studies in chronic infections under constant antibiotic selective pressure. PMID- 22322353 TI - Production and evaluation of antibodies and phage display-derived peptide ligands for immunomagnetic separation of Mycobacterium bovis. AB - This study describes the development and optimization of an immunomagnetic separation (IMS) method to isolate Mycobacterium bovis cells from lymph node tissues. Gamma-irradiated whole M. bovis AF2122/97 cells and ethanol-extracted surface antigens of such cells were used to produce M. bovis-specific polyclonal and monoclonal antibodies in rabbits and mice. They were also used to generate M. bovis-specific peptide ligands by phage display biopanning. The various antibodies and peptide ligands obtained were used to coat MyOne tosyl-activated Dynabeads (Life Technologies), singly or in combination, and evaluated for IMS. Initially, M. bovis capture from Middlebrook 7H9 broth suspensions (concentration range, 10 to 10(5) CFU/ml) was evaluated by IMS combined with an M. bovis specific touchdown PCR. IMS-PCR results and, subsequently, IMS-culture results indicated that the beads with greatest immunocapture capability for M. bovis in broth were those coated simultaneously with a monoclonal antibody and a biotinylated 12-mer peptide. These dually coated beads exhibited minimal capture (mean of 0.36% recovery) of 12 other Mycobacterium spp. occasionally encountered in veterinary tuberculosis (TB) diagnostic laboratories. When the optimized IMS method was applied to various M. bovis-spiked lymph node matrices, it demonstrated excellent detection sensitivities (50% limits of detection of 3.16 and 57.7 CFU/ml of lymph node tissue homogenate for IMS-PCR and IMS-culture, respectively). The optimized IMS method therefore has the potential to improve isolation of M. bovis from lymph nodes and hence the diagnosis of bovine tuberculosis. PMID- 22322354 TI - Contribution of amoebic coculture to recovery of Legionella isolates from respiratory samples: prospective analysis over a period of 32 months. AB - We evaluated the contribution of amoebic coculture to the recovery of Legionella spp. from 379 respiratory samples. The sensitivity of axenic culture was 42.1%. The combination of axenic culture with amoebic coculture increased the Legionella isolation rate to 47.1%. Amoebic coculture was particularly efficient in isolating Legionella spp. from respiratory samples contaminated with oropharyngeal flora. PMID- 22322355 TI - First report of the Shiga toxin 1 gene in sorbitol-fermenting Escherichia coli O157:H-. PMID- 22322356 TI - QTLs for murine red blood cell parameters in LG/J and SM/J F(2) and advanced intercross lines. AB - Red blood cells are essential for oxygen transport and other physiologic processes. Red cell characteristics are typically determined by complete blood counts which measure parameters such as hemoglobin levels and mean corpuscular volumes; these parameters reflect the quality and quantity of red cells in the circulation at any particular moment. To identify the genetic determinants of red cell parameters, we performed genome-wide association analysis on LG/J*SM/J F2 and F34 advanced intercross lines using single nucleotide polymorphism genotyping and a novel algorithm for mapping in the combined populations. We identified significant quantitative trait loci for red cell parameters on chromosomes 6, 7, 8, 10, 12, and 17; our use of advanced intercross lines reduced the quantitative trait loci interval width from 1.6- to 9.4-fold. Using the genomic sequences of LG/J and SM/J mice, we identified nonsynonymous coding single nucleotide polymorphisms in candidate genes residing within quantitative trait loci and performed sequence alignments and molecular modeling to gauge the potential impact of amino acid substitutions. These results should aid in the identification of genes critical for red cell physiology and metabolism and demonstrate the utility of advanced intercross lines in uncovering genetic determinants of inherited traits. PMID- 22322357 TI - The HSP co-inducer BGP-15 can prevent the metabolic side effects of the atypical antipsychotics. AB - Weight gain and dysfunction of glucose and lipid metabolism are well-known side effects of atypical antipsychotic drugs (AAPD). Here, we address the question whether a heat-shock protein (HSP) co-inducer, insulin sensitizer drug candidate, BGP-15, can prevent AAPD-induced glucose, lipid, and weight changes. We also examined how an AAPD alters HSP expression and whether BGP-15 alters that expression. Four different experiments are reported on the AAPD BGP-15 interventions in a human trial of healthy men, a rodent animal model, and an in vitro adipocyte cell culture system. Olanzapine caused rapid insulin resistance in healthy volunteers and was associated with decreased level of HSP72 in peripheral mononuclear blood cells. Both changes were restored by the administration of BGP-15. In Wistar rats, weight gain and insulin resistance induced by clozapine were abolished by BGP-15. In 3T3L1 adipocytes, clozapine increased intracellular fat accumulation, and BGP-15 inhibited this process. Taken together, our results indicate that BGP-15 inhibits multiple metabolic side effects of atypical antipsychotics, and this effect is likely to be related to its HSP co-inducing ability. PMID- 22322358 TI - The protective and immunomodulatory effects of hypothalamic proline-rich polypeptide galarmin against methicillin-resistant Staphylococcus aureus infection in mice. AB - The present research summarizes the protective and immunomodulatory activity of hypothalamic proline-rich polypeptide galarmin against methicillin-resistant Staphylococcus aureus (MRSA). The protective effect of galarmin was shown on MRSA infected animals' survival and weight loss recovery. The immunological impact of galarmin was evaluated in terms of immunocompetent cell recruitment, serum immunoglobulins, complement components C3 and C4, and pro- and anti-inflammatory cytokines (IL-6, IL-8, IL-10, IL-1b, TNFa, and KC) secretion. Galarmin efficiently protects mice against lethal MRSA infection (100% of survival vs. 0% in the untreated group) when intramuscularly injected 24 h before infection and during the 1-h post-infection period at a concentration of 1 MUg per mouse, while its higher concentrations (5 and 10 MUg) were protective when injected in parallel to the infection process. The protective effect of galarmin was not due to a direct effect on MRSA, but should be attributed to an action on the host response to infection. Galarmin significantly increased and modulated the levels of IL-6, IL-8, IL-1b, IL-10, and KC in both peritoneal lavages and blood, leukocyte and platelet counts, lymphocytes percentage, serum IgM and IgG, and complement C3 and C4 components secretion. The experimental results allow concluding that galarmin is a powerful immunomodulatory and protective agent for the in vivo prophylaxis and treatment of MRSA-induced infection. PMID- 22322359 TI - Microcolonies in fluoroquinolone agar proportion susceptibility testing of Mycobacterium tuberculosis: an indicator of drug resistance. AB - Microcolony growth of Mycobacterium tuberculosis on agar proportion susceptibility testing is neither well-defined nor previously reported with fluoroquinolone susceptibility testing. We describe here M. tuberculosis microcolony growth with fluoroquinolones, and assess its clinical significance. We screened 797 M. tuberculosis isolates for ofloxacin resistance (2.0 MUg/mL) by agar proportion; 19 ofloxacin-resistant and 38 ofloxacin-susceptible isolates were selected for more detailed susceptibility testing with ofloxacin, ciprofloxacin, levofloxacin (all at 2.0 MUg/mL) and moxifloxacin (0.5 MUg/mL). The 57 isolates were also tested at two concentrations both above and below the critical concentrations. Microcolonies were defined as colonies 0.2-0.4 mm in diameter; confirmed microcolonies were present on repeat testing. Of the 57 isolates tested in detail, 7 grew microcolonies, of which 2 (0.3% of all isolates tested) had confirmed microcolonies on repeat testing (6 tests performed, and microcolonies were present on at least 4). Both M. tuberculosis isolates were ofloxacin-resistant on screening, and had ofloxacin minimum inhibitory concentration (MIC) >8 MUg/mL. The five other isolates were ofloxacin-susceptible on screening, but had regular colony growth (i.e., resistance) at the drug concentration that initially resulted in microcolonies (ofloxacin 0.5 or 1.0 MUg/mL). Microcolonies were observed infrequently with fluoroquinolone susceptibility testing, but when confirmed, they were associated with drug resistance. PMID- 22322360 TI - Synthesis of 2-aminofurans and 2-unsubstituted furans via carbenoid-mediated [3 + 2] cycloaddition. AB - An efficient dual synthetic manifold for 2-aminofurans and 2-unsubstituted furans has been developed. The carbenoid-mediated [3 + 2] cycloaddition of copper carbenoids with enamines provides 2-amino-2,3-dihydrofurans which serve as common intermediates for both 2-aminofurans and 2-unsubstituted furans. PMID- 22322361 TI - Radiation-induced double strand breaks and subsequent apoptotic DNA fragmentation in human peripheral blood mononuclear cells. AB - In case of accidental radiation exposure or a nuclear incident, physical dosimetry is not always complete. Therefore, it is important to develop tools that allow dose estimates and determination that are based on biological markers of radiation exposure. Exposure to ionizing radiation triggers a large-scale activation of specific DNA signaling and repair mechanisms. This includes the phosphorylation of gammaH2AX in the vicinity of a double-strand break (DSB). A DNA DSB is a cytotoxic form of DNA damage, and if not correctly repaired can initiate genomic instability, chromosome aberrations, mutations or apoptosis. Measurements of DNA DSBs and their subsequent repair after in vitro irradiation has been suggested to be of potential use to monitor cellular responses. The bone marrow and the blood are known to be the most radiosensitive tissues of the human body and can therefore be of particular importance to find radiation-induced biological markers. In the present study, changes in H2AX phosphorylation and apoptosis of irradiated human peripheral blood mononuclear cells (PBMCs) were analyzed. Freshly isolated PBMCs from healthy donors were irradiated with X-rays (0.1, 0.25, 0.5, 1, 2 and 4 Gy). The phosphorylation of gammaH2AX was measured at different time points (0, 0.25, 1, 2, 4, 6 and 24 h) after irradiation. We detected a linear dose-dependency of gammaH2AX phosphorylation measured by gammaH2AX foci scoring using immunofluorescence microscopy as well as by gammaH2AX fluorescence detection using flow cytometry. Apoptosis was detected by measuring DNA fragmentation at different time points (0, 24, 48, 72, 96 h) after X-irradiation using DNA ladder gel electrophoresis. The apoptotic DNA fragmentation increased in a dose-dependent manner. In conclusion, DNA DSBs and subsequent apoptotic DNA fragmentation monitoring have potential as biomarkers for assessing human exposure in radiation biodosimetry. PMID- 22322362 TI - Whole blood RNA expression profiles in ovarian cancer patients with or without residual tumors after primary cytoreductive surgery. AB - Significant improvements in the treatment results of ovarian cancer have been achieved during the last decades, but further improvements require additional methods identifying signs of the disease and its biological behavior, preferably by a simple blood test. We hypothesized that peripheral blood leukocytes may express genes that carry such clinical information. Therefore, we studied the relative gene expressions of 168 cancer- and metastasis-specific genes in blood samples from ovarian cancer patients with different prognoses after primary cytoreductive surgery. Total RNA was extracted from whole blood and the relative gene expression profile of 168 genes were analyzed using real-time qPCR assays. Two groups of patients were analyzed; one group with residual tumor mass after primary surgery, and one group where the tumor was macroscopically radically resected, resulting in no visible tumor mass left behind. The group with the remaining tumor mass after surgery showed significantly different gene expression profiles compared to the group with no remaining tumor mass. Differences were noted for the metastasis associated 1 family, member 2 gene (MTA2), the TNF, alpha-catenin, interleukin 1beta, the KiSS-1 metastasis suppressor and the matrix metallo-proteinase 10 genes. All genes were downregulated with a fold-change between 1.15 to 1.57; there were no upregulated genes. Thus, a signature of genes involved in metastasis, invasion and inflammation was found to be significantly downregulated in native unstimulated blood leukocytes from ovarian cancer patients with a poor prognosis. Preoperatively it may serve as a guide to the biology of the tumor and postoperatively in the optimization of adjuvant treatment of ovarian cancer patients. PMID- 22322363 TI - The impact of intraoperative vaccination with IL-12 modified autologous tumor cells in the Lewis lung carcinoma mouse model. AB - PURPOSE: To improve immunological defense of tumors, we investigated the effect of intraoperative vaccination with IL-12 cDNA transfected cells in an autologous mouse tumor model. METHODS: Tumors derived from autologous Lewis lung carcinoma cells were established in C57/BL6 mice. At day seven, the tumors were surgically removed. Simultaneously, the mice were vaccinated intraoperatively with Lewis lung carcinoma cells transfected with an IL-12-encoding pRSC construct or with the empty plasmid, or with dead cells either intrasplenically (i.s.) or subcutaneously (s.c.). Control mice did not obtain vaccination. Tumor re-growth, survival, and metastasis were monitored. Mice with no tumor re-growth underwent a second tumor implantation. The same parameters were examined. RESULTS: After tumor resection and vaccination tumors reappeared in 60.0% of the animals of the control group. Lowest tumor reoccurrence rates of 41.4 and 43.5% were seen in animals receiving IL-12 pRSC cells either i.s. or s.c. Survival tended to be enhanced in all vaccinated animals compared with the control group. Following R0 tumor resection, the rate of tumor-free survivors was highest when IL-12 pRSC cells were given i.s. (73%, control 45%). 37-59% of the mice of the therapy groups did not develop a tumor, that is, they were tumor-free survivors. These mice underwent a second tumor implantation 120 days after tumor resection and vaccination. Tumor growth was significantly delayed in mice receiving IL-12 pRSC cells. CONCLUSIONS: Intraoperative autologous whole-cell vaccination is practicable and proved to have anti-tumor potential, and therefore, it could be an additional option in adjuvant cancer therapy. PMID- 22322365 TI - Correlation of two capsule endoscopy scoring systems with fecal calprotectin: does it really matter? PMID- 22322364 TI - Combination of Temsirolimus and tyrosine kinase inhibitors in renal carcinoma and endothelial cell lines. AB - PURPOSE: Multitargeted tyrosine kinase inhibitors (TKIs) (such as Sunitinib and Sorafenib) and mTOR inhibitors (such as Temsirolimus) are effective in treating metastatic clear-cell renal cell carcinoma (CCRCC), by acting on different pathways in both tumour and endothelial cells. A study of their combined effect could be of major interest. METHODS: We studied endothelial and CCRCC cell lines treated with Sunitinib, Sorafenib, Temsirolimus and 2 drug combinations: Sunitinib-Temsirolimus and Sorafenib-Temsirolimus. We studied inhibition of proliferation with an MTT assay under normoxia and hypoxia, VEGF expression by quantitative RT-PCR and ELISA, and angiogenesis with a Matrigel assay. RESULTS: TKIs and Temsirolimus inhibited proliferation of endothelial and tumour cell lines and inhibited angiogenesis. Anti-proliferative effects were more significant on cell lines with VHL gene inactivation and under hypoxic conditions. VEGF expression was induced by TKIs, but inhibited by Temsirolimus. The Sunitinib/Temsirolimus combination had synergistic or additive effects on the proliferation of tumour and endothelial cell lines. The Sorafenib-Temsirolimus combination had additive effects on the proliferation of most tumour cell lines, but not endothelial cell lines. Both combinations had additive effects on the inhibition of angiogenesis. CONCLUSION: In our model, Sunitinib, Sorafenib and Temsirolimus had anti-tumour and anti-angiogenic effects. The combinations of Sunitinib or Sorafenib with Temsirolimus had additive or synergistic effects on the inhibition of tumour and endothelial cell proliferation, and on the inhibition of angiogenesis. This work could lead to new trials with lower-dose combinations to prevent side effects and enhance efficacy. PMID- 22322366 TI - Rate-dependent effects of vernakalant in the isolated non-remodeled canine left atria are primarily due to block of the sodium channel: comparison with ranolazine and dl-sotalol. AB - BACKGROUND: Several clinical trials have shown that vernakalant is effective in terminating recent onset atrial fibrillation (AF). The electrophysiological actions of vernakalant are not fully understood. METHODS AND RESULTS: Here we report the results of a blinded study comparing the in vitro canine atrial electrophysiological effects of vernakalant, ranolazine, and dl-sotalol. Action potential durations (APD(50,75,90)), effective refractory period (ERP), post repolarization refractoriness (PRR), maximum rate of rise of the action potential (AP) upstroke (V(max)), diastolic threshold of excitation (DTE), conduction time (CT), and the shortest S(1)-S(1) permitting 1:1 activation (S(1)-S(1)) were measured using standard stimulation and microelectrode recording techniques in isolated normal, non-remodeled canine arterially perfused left atrial preparations. Vernakalant caused variable but slight prolongation of APD(90) (P=not significant), but significant prolongation of APD(50) at 30 MUmol/L and rapid rates. In contrast, ranolazine and dl-sotalol produced consistent concentration- and reverse rate-dependent prolongation of APD(90). Vernakalant and ranolazine caused rate-dependent, whereas dl-sotalol caused reverse rate dependent, prolongation of ERP. Significant rate-dependent PRR developed with vernakalant and ranolazine, but not with dl-sotalol. Other sodium channel mediated parameters (ie, V(max), CT, DTE, and S(1)-S(1)) also were depressed significantly by vernakalant and ranolazine, but not by dl-sotalol. Only vernakalant elevated AP plateau voltage, consistent with blockade of ultrarapid delayed rectified potassium current and transient outward potassium current. CONCLUSIONS: In isolated canine left atria, the effects of vernakalant and ranolazine were characterized by use-dependent inhibition of sodium channel mediated parameters, and those of dl-sotalol by reverse rate-dependent prolongation of APD(90) and ERP. This suggests that during the rapid activation rates of AF, the I(Na) blocking action of the mixed ion channel blocker vernakalant takes prominence. This mechanism may explain vernakalant's anti-AF efficacy. PMID- 22322367 TI - Three potential mechanisms for failure of high intensity focused ultrasound ablation in cardiac tissue. AB - BACKGROUND: High intensity focused ultrasound (HIFU) has been introduced for treatment of cardiac arrhythmias because it offers the ability to create rapid tissue modification in confined volumes without directly contacting the myocardium. In spite of the benefits of HIFU, a number of limitations have been reported, which hindered its clinical adoption. METHODS AND RESULTS: In this study, we used a multimodal approach to evaluate thermal and nonthermal effects of HIFU in cardiac ablation. We designed a computer controlled system capable of simultaneous fluorescence mapping and HIFU ablation. Using this system, linear lesions were created in isolated rabbit atria (n=6), and point lesions were created in the ventricles of whole-heart (n=6) preparations by applying HIFU at clinical doses (4-16 W). Additionally, we evaluate the gap size in ablation lines necessary for conduction in atrial preparations (n=4). The voltage sensitive dye di-4-ANEPPS was used to assess functional damage produced by HIFU. Optical coherence tomography and general histology were used to evaluate lesion extent. Conduction block was achieved in 1 (17%) of 6 atrial preparations with a single ablation line. Following 10 minutes of rest, 0 (0%) of 6 atrial preparations demonstrated sustained conduction block from a single ablation line. Tissue displacement of 1 to 3 mm was observed during HIFU application due to acoustic radiation force along the lesion line. Additionally, excessive acoustic pressure and high temperature from HIFU generated cavitation, causing macroscopic tissue damage. A minimum gap size of 1.5 mm was found to conduct electric activity. CONCLUSIONS: This study identified 3 potential mechanisms responsible for the failure of HIFU ablation in cardiac tissues. Both acoustic radiation force and acoustic cavitation, in conjunction with inconsistent thermal deposition, can increase the risk of lesion discontinuity and result in gap sizes that promote ablation failure. PMID- 22322368 TI - Layered spherical carbon composites with nanoparticles of different metals grown simultaneously inside and outside. AB - We report a general one-step route to place nanoparticles (NPs) of different noble metals controllably into interior or surface locations of submicron nanoporous carbon spheres (CSs). In particular, Pd and Au NPs can be easily put either inside or outside of the CSs by selecting these metals' differently charged precursor ions. Employing mixed precursor solutions, the method allows different metals to grow simultaneously yet selectively in the separate locations, thus resulting in composites with a complex layered structure, for example Pd or Au outside and Ag inside, Au or Pt outside and Pd inside, and other combinations. The synthesis is fast and needs no additional steps like a functionalization of surfaces. It crucially involves microwave heating, the power setting of which further influences the locations and sizes of the NPs especially in the interior of the amorphous carbon matrix. The three-dimensional composite structures are analyzed by transmission electron microscopy and energy dispersed x-ray spectroscopy combined with quantitative analysis by comparison with simulation. The UV-visible absorption of monometallic and layered composites is compared. The involved mechanisms leading to the selective decoration are discussed; important aspects being the charge of the precursor ions and selective microwave absorption. PMID- 22322369 TI - Myeloperoxidase exacerbates secondary injury by generating highly reactive oxygen species and mediating neutrophil recruitment in experimental spinal cord injury. AB - STUDY DESIGN: An animal study using myeloperoxidase-knockout (MPO-KO) mice to examine the in vivo role of myeloperoxidase (MPO) in spinal cord injury (SCI). OBJECTIVE: To clarify the influence of MPO on inflammatory cell infiltration, tissue damage, and functional recovery after SCI. SUMMARY OF BACKGROUND DATA: MPO is considered to be important in spreading tissue damage after SCI because it generates strong neurotoxic oxidant hypochlorous acid (HOCl). However, the direct involvement of MPO in the pathophysiology of SCI remains to be elucidated. METHODS: To compare the inflammatory reaction, tissue damage, and neurological recovery after SCI, a moderate contusion injury was created at the ninth thoracic level in MPO-KO mice and wild-type mice. A HOCl-specific probe solution was injected into the lesion epicenter to assess the spatiotemporal production of MPO derived HOCl. Inflammatory reactions were quantified by flow cytometry and quantitative real-time polymerase chain reaction, and tissue damage was evaluated by an immunohistochemical analysis. The motor function recovery was assessed by the open-field locomotor score. RESULTS: Prominent production of HOCl was observed during the hyperacute phase of SCI at the lesion site in the wild-type mice; however, little expression was observed in the MPO-KO mice. In this phase, the number of infiltrated neutrophils was significantly reduced in the MPO-KO mice compared with the wild-type mice. In addition, significant differences were observed in the expression levels of proinflammatory cytokines and apoptosis related genes between 2 groups. In the histological sections, fewer terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive apoptotic cells and more spared myelin were observed at the lesion site in MPO-KO mice. Consistent with these results, better functional recovery was observed in the MPO KO mice than in the wild-type mice after SCI. CONCLUSION: These results clearly indicated that MPO exacerbated secondary injury and impaired the functional recovery not only by generating strong oxidant HOCl, but also by enhancing neutrophil infiltration after SCI. PMID- 22322370 TI - Which Lenke 1A curves are at the greatest risk for adding-on... and why? AB - STUDY DESIGN: Multicenter review of prospectively collected data. OBJECTIVE: The purpose of this study was to evaluate the incidence of distal adding-on and associated risk factors in each of the 2 Lenke 1A curve patterns. SUMMARY OF BACKGROUND DATA: Previous work has demonstrated 2 distinct Lenke 1A curve patterns on the basis of the tilt of L4 (1A-L and 1A-R) that are different in form and treatment. METHODS: A query of a prospective multicenter adolescent idiopathic scoliosis database identified 195 patients with Lenke 1A curves. Patients were grouped on the basis of the direction of the L4 vertebral tilt: 1A L (left) and 1A-R (right). The incidences as well as clinical and radiographical risk factors for adding-on were identified for each group. Adding-on was defined as an increase in the Cobb angle of at least 5 degrees and distalization of the end vertebra of the thoracic curve or a change in disc angulation of 5 degrees or greater below the lowest instrumented vertebra from the first erect to 2-year postoperative radiographs. RESULTS: Forty (21%) patients met the criteria for adding-on. The average increase in Cobb angle was 11.9 degrees for those categorized as having adding-on compared with 3.8 degrees in the non-adding-on group. Lenke 1A-R curves were 2.2 times more likely to experience adding-on than 1A-L curves. In the 1A-R curves, patients who added-on were fused at an average of 1.6 levels proximal to the neutral vertebra versus an average of 0.9 levels proximal to the neutral vertebra for the patients who did not add-on (P = 0.023). Patients who added-on were fused at an average of 2.5 levels above stable versus 2.1 levels above stable in those who did not (P = 0.06). Age and skeletal maturity were not identified as risk factors in the 1A-R curves. In 1A-L curves, younger (12.7 vs. 14.7 yr, P = 0.002) and less skeletally mature patients based on Risser grading (70% vs. 14% Risser 0, P = 0.004) were more likely to experience adding-on. CONCLUSION: Understanding the difference between Lenke 1A-L and 1A-R curve types may be helpful in preventing the adding-on phenomena postoperatively. To prevent adding-on in 1A-R curves, we recommend fusing distally to 1 level above the neutral vertebra or 1 to 2 levels above the stable vertebra. In 1A-L curves, adding-on may simply be a need to balance some lumbar curve progression in a young, skeletally immature patient. PMID- 22322372 TI - Translaminar screw fixation in the subaxial cervical spine: quantitative laminar analysis and feasibility of unilateral and bilateral translaminar virtual screw placement. AB - STUDY DESIGN: Morphometric and volumetric analyses and virtual screw placement. OBJECTIVE: The aim of the study was to (1) define the morphometric and volumetric dimensions of the laminae of C3-C7 and (2) analyze the feasibility of unilateral and bilateral translaminar screw placement at C3-C7. SUMMARY OF BACKGROUND DATA: Previous studies on translaminar screw fixation have primarily focused on upper cervical and thoracic fixation. Most studies have been conducted on the subaxial cervical vertebrae in the pediatric population and a few in the adult population. In this study, we used computed tomographic (CT) scans to calculate the spatial anatomical environment for translaminar screws at C3-C7. We also determined the feasibility of translaminar screw placement at C3-C7 for clinical applicability. METHODS: Morphometric and volumetric analyses were performed on CT scans of the C3-C7 laminae in 25 male and 25 female patients. A total of 2000 morphometric and 1000 volumetric measurements were performed. The feasibility analysis was performed using unilateral and bilateral virtual screw placement via BrainLAB software (BrainLAB AG, Heimstetten, Germany) on the same CT scans. RESULTS: Male patients had significantly (P < 0.05) longer translaminar lengths (C5-C7), sagittal-diagonal measurements (C3-C7), and larger volumes (C6-C7) than female patients. Unilaterally, C7 showed 3.5-mm translaminar screw acceptance rates of 100%, C6 showed high acceptance rates (>64%), and C3-C5 showed lower acceptance rates (<52%). C7 accepted bilateral placement at a high rate (96% men, 84% women). C3 and C6 accepted bilateral screws at low placement rates (8%-24%). C4 and C5 never accepted bilateral translaminar screw placement. CONCLUSION: Subaxial cervical unilateral translaminar screw placement is a potentially safe and effective technique to use in conjunction with preoperative CT scanning for all vertebral levels. The same is true for bilateral placement at C7 but not at C3-C6. A prospective study to evaluate the long-term outcomes of translaminar fixation at all vertebral levels is currently underway. PMID- 22322373 TI - Asymmetric degeneration of paravertebral muscles in patients with degenerative lumbar scoliosis. AB - STUDY DESIGN: A prospective observational study. OBJECTIVE: To evaluate the paravertebral muscle (PVM) degeneration in patients with degenerative lumbar scoliosis (DLS), using magnetic resonance imaging. SUMMARY OF BACKGROUND DATA: Several studies have described the histological and morphological changes to the PVM in patients with chronic low back pain and lumbar radiculopathy. However, there is little knowledge about the PVM changes in patients with DLS. METHODS: Fifty-seven patients with lumbar spinal stenosis (LSS) with DLS (DLS group) and 50 control patients with LSS without DLS (LSS group) were examined. The cross sectional area (CSA) and percentage of fat infiltration area (%FIA) of the bilateral multifidus and longissimus muscles at the L1-S1 levels were measured using T2-weighted axial magnetic resonance imaging and computer software. A multifidus muscle biopsy and histological evaluation were performed in some patients. RESULTS: In the DLS group, the CSA of the multifidus muscle was significantly smaller and the %FIA of both muscles was significantly higher on the concave side than on the convex side at all levels (P < 0.0001 for each). These differences were also found in the longissimus muscles at the L4-L5 and L5 S1 levels (P < 0.0001 for each). Histologically, the multifidus muscle exhibited reductions in the muscle fiber size and number of nuclei on the concave side. In the LSS group, the total CSA and %FIA did not differ significantly between the left and right sides. However, in patients with unilateral radiculopathy, the CSA of the multifidus muscle was significantly smaller (P < 0.05) and the %FIA of both muscles was significantly higher (P < 0.05) on the symptomatic side, especially at 1 level below. CONCLUSION: This observational study with magnetic resonance imaging and histology showed that muscle degeneration was more common on the concave side in patients with DLS. Radiculopathy and spinal deformity may contribute to the PVM degeneration. PMID- 22322374 TI - Spinal cord tumor surgery--importance of continuous intraoperative neurophysiological monitoring after tumor resection. AB - STUDY DESIGN: A retrospective clinical analysis of patients operated on for spinal tumors. OBJECTIVE: To report on the importance of intraoperative neurophysiological monitoring (INM) throughout the entire surgical procedure. SUMMARY OF BACKGROUND DATA: Postoperative neurological deterioration, despite unaltered neurophysiological monitoring, has been reported. This might be related to timely restricted monitoring. Thus, the likelihood of alterations in INM from positioning to wound closure was analyzed. METHODS: Two hundred three patients (age range, 54.9 +/- 17.4 yr) undergoing intradural tumor removal were sampled in a prospective database and analyzed for the occurrence of alterations in intraoperative somatosensory- and motor-evoked potentials. RESULTS: INM alterations were observed in 47 of 203 (23.2%) patients. These alterations were related to tumor resection in 29 (14.3%) cases, whereas these were unrelated to tumor removal in 18 patients: laminotomy in 5 (2.5%) patients, dura opening in 7 (3.5%) patients, dura closure in 5 (2.5%) patients, and laminoplasty in 1 (0.5%) patient caused INM changes. CONCLUSION: This study demonstrates that monitoring beyond tumor resection is of essential importance in order to detect all critical phases of surgical procedure and to counteract accordingly. PMID- 22322375 TI - Warning thresholds on the basis of origin of amplitude changes in transcranial electrical motor-evoked potential monitoring for cervical compression myelopathy. AB - STUDY DESIGN: A retrospective analysis of prospectively collected data from consecutive patients undergoing transcranial electrical motor-evoked potential (TCE-MEP: compound muscle action potentials) monitoring during cervical spine surgery. OBJECTIVE.: To divide the warning threshold of TCE-MEP amplitude changes on the basis of origin into the spinal tract and spinal segments and decide warning thresholds for each. SUMMARY OF BACKGROUND DATA: The parameter commonly used for the warning threshold in TCE-MEP monitoring is wave amplitude, but amplitude changes have not been examined by anatomical origin. METHODS: Intraoperative TCE-MEP amplitude changes were reviewed for 357 patients with cervical myelopathy. Most of the patients were monitored by transcranial electrical stimulated spinal-evoked potential combined with TCE-MEP. The warning threshold of TCE-MEP was taken as waveform disappearance. For each patient, amplitude changes were separated, according to origin, into the spinal tract and spinal segments and compared with clinical outcome. RESULTS: Assessable TCE-MEP waves were obtained in 350 cases. Disappearance of TCE-MEP waves, which were innervated by the spinal levels exposed to the surgical invasion, was seen in 11 cases. Disappearance of TCE-MEPs, which were innervated by the spinal levels inferior to them, was seen in 43 cases. There was no postoperative motor deficit in those cases. However, such deficits caused by spinal segment injury were seen in 2 cases, which showed that intraoperative amplitude decreased to 4.5% and 27%. CONCLUSION: If we had established the warning threshold as 30% of the control amplitude, we would likely have prevented both cases of postoperative motor deficits, but 106 (30.3%) cases would have become positive cases. If we had established the warning threshold separately as wave disappearance for the spinal tract and 30% of the control amplitude for the spinal segments, sensitivity and specificity would have been 100% and 83.7%, respectively. Dividing the warning threshold on the basis of origin of amplitude changes could reduce false-positive cases and prevent intraoperative injuries. PMID- 22322376 TI - Hydrostatic comparison of nonpenetrating titanium clips versus conventional suture for repair of spinal durotomies. AB - STUDY DESIGN: Biomechanics. OBJECTIVE: To compare the hydrostatic strength of suture and nonpenetrating titanium clip repairs of standard spinal durotomies. SUMMARY OF BACKGROUND DATA: Dural tears are a frequent complication of spine surgery and can be associated with significant morbidity. Primary repair of durotomies with suture typically is attempted, but a true watertight closure can be difficult to obtain because of leakage through suture tracts. Nonpenetrating titanium clips have been developed for vascular anastomoses and provide a close apposition of the tissues without the creation of a suture tract. METHODS: Twenty four calf spines were prepared with laminectomies and the spinal cord was evacuated leaving an intact dura. After Foley catheters were inserted from each end and inflated adjacent to a planned dural defect, the basal flow rate was measured and a 1-cm longitudinal durotomy was made with a scalpel. Eight repairs were performed for each material, which included monofilament suture, braided suture, and nonpenetrating titanium clips. The flow rate at 30, 60, and 90 cm of water and the time needed for each closure were measured. RESULTS: There was no statistically significant difference in the baseline leak rate for all 3 groups. There was no difference in the leakage rate of durotomies repaired with clips and intact specimens at any pressure. Monofilament and braided suture repairs allowed significantly more leakage than both intact and clip-repaired specimens at all pressures. The difference in leak rate increased as the pressure increased. Closing the durotomy with clips took less than half the time of closure with suture. CONCLUSION: Nonpenetrating titanium clips provide a durotomy closure with immediate hydrostatic strength similar to intact dura whereas suture repair with either suture was significantly less robust. The use of titanium clips was more rapid than that of suture repair. PMID- 22322377 TI - Preliminary biomechanical proof of concept for a hybrid locking plate/variable pitch screw construct for anterior fixation of type II odontoid fractures. AB - STUDY DESIGN: A human cadaveric biomechanical proof-of-concept study. OBJECTIVE: To test whether adding a locking plate to the anterior surface of C2 attaching directly to the interfragmentary screw may reduce potential for anterior screw cutout and improve construct strength. SUMMARY OF BACKGROUND DATA: The most common mode of failure for screw fixation of dens fractures is via cutout at the anterior body of C2. METHODS: A human, cadaveric model of type II dens fractures was created and fixed using either a headless, fully threaded variable pitch screw (FTVPS) or a screw with an attachable locking plate construct (LPC). Following quasistatic loading to failure, stiffness and load to failure were compared using t tests. Mode of failure was determined from radiographical and gross inspection. RESULTS: Load to failure was greater for the LPC than for the FTVPS alone (498 N vs. 362 N, P = 0.04). The LPC consistently failed via compression of cancellous bone posterior to the lag screw, whereas the FTVPS constructs failed via cutout of the screw from the anterior C2 body. CONCLUSION: Locking plate supplementation of anterior screw fixation of type II odontoid fractures improves construct strength and changes the failure mechanism from anterior screw cutout to posterior displacement of the screw. An attachable locking plate/interfragmentary screw construct may improve clinical outcomes for these fractures. PMID- 22322378 TI - Intragastric balloon fundal or antral position affects weight loss and tolerability. AB - BACKGROUND: Intragastric balloons (BIB) are routinely used for weight reduction. They should be placed to the gastric fundus, as this place is believed more effective for achievement of satiety and thus weight reduction. The aim of the present study was to evaluate whether the balloon position may affect 6-month weight loss as well as first-month side-effects, i.e. nausea, vomiting, and gastroesophageal reflux. METHODS: From a total of 158 BIB-treated obese individuals, 105 females were found eligible, since the balloon in the stomach was found upon removal in the same position (fundus or antrum) placed at the time of insertion. These subjects were divided into fundus and antral groups. Data related to obesity were recorded on day 0 and upon BIB removal, 6 months thereafter. Data related to transient side-effects (nausea, vomiting, gastroesophageal reflux) were recorded on days 0-3, 7, and weekly thereafter, for 1 month. RESULTS: BIB placed in the antrum was found to have significantly better results on weight loss parameters, while nausea, vomiting (p = 0.02) as well as gastroesophageal reflux still remained up to the fourth week in a relation to the fundus group. Similarly, the rate of gastric distension was found significantly increased (p = 0.001) during the days 1-3 in fundus group in relation to antrum, followed by a progressive decrease in both groups. CONCLUSIONS: Intragastric balloon placed in the antrum lead to better results in weight reduction but to longer duration of tolerability-related side-effects, i.e., nausea, vomiting, and gastroesophageal reflux. PMID- 22322379 TI - Epithelial mesenchymal transition correlates with CD24+CD44+ and CD133+ cells in pancreatic cancer. AB - The epithelial-mesenchymal transition (EMT) has been linked to induction of a stem-cell like phenotype, characterized by altered cell surface marker expression and increased tumor formation. The aim of this study was to investigate whether EMT correlates with CD24+CD44+ and CD133+ cells in pancreatic cancer. The morphology of untreated and gemcitabine-treated SW1990 gemcitabine-resistant cells and normal SW1990 cells were compared. NF-kappaB p65 expression was knocked down using siRNA. Vimentin and E-cadherin expression were analyzed using western blotting, and CD24+CD44+, CD133+ cells were quantified by FACS. Additionally, immunohistochemistry of EMT-associated markers and stem cell-associated markers were performed in 41 cases of human pancreatic ductal adenocarcinoma. In SW1990 gemcitabine-resistant cells, gemcitabine induced a mesenchymal cell phenotype, expression of EMT-related molecular markers and increased CD24+CD44+ and CD133+ cells compared to untreated SW1990 gemcitabine-resistant and SW1990 cells. Knockdown of NF-kappaB p65 inhibited the ability of gemcitabine to increase the proportion of CD24+CD44+ or CD133+ cells and expression of EMT-related molecular markers. In human pancreatic ductal adenocarcinoma, significant correlations were observed between expression of the EMT-associated markers vimentin and E cadherin, and stem cell-associated markers CD24, CD133 and CD44. This study demonstrated that EMT correlated with CD24+CD44+ and CD133+ cells in pancreatic cancer. This study also suggests that EMT may induce cancer stem-like cells in pancreatic cancer, with different degrees of EMT probability inducing different proportions of CD24+CD44+ and CD133+ cells. PMID- 22322380 TI - Biochemical analysis with the expanded genetic lexicon. AB - The information used to build proteins is stored in the genetic material of every organism. In nature, ribosomes use 20 native amino acids to synthesize proteins in most circumstances. However, laboratory efforts to expand the genetic repertoire of living cells and organisms have successfully encoded more than 80 nonnative amino acids in E. coli, yeast, and other eukaryotic systems. The selectivity, fidelity, and site-specificity provided by the technology have enabled unprecedented flexibility in manipulating protein sequences and functions in cells. Various biophysical probes can be chemically conjugated or directly incorporated at specific residues in proteins, and corresponding analytical techniques can then be used to answer diverse biological questions. This review summarizes the methodology of genetic code expansion and its recent progress, and discusses the applications of commonly used analytical methods. PMID- 22322381 TI - Preparation and characterization of microcapsules based on biodegradable polymers: pectin/casein complex for controlled drug release systems. AB - Controlled release of drugs is an important strategy to diminish the drug dose and adverse side effects. Aqueous mixtures of polysaccharides and proteins are usually unstable above a certain biopolymer concentration and phase separation occurs either because of repulsive (segregative) or attractive (associative) interactions. Herein, pectin/casein microcapsules were prepared by complex coacervation aiming at prolonged drug release. The morphological characteristics, particle size, distribution, and release kinetics of microcapsules were studied using as a model the hydrophilic drug acetaminophen. It was detected that complexation of pectin/casein particles occurs at pH values lower than 6, resulting in the formation of spherical particles after spray drying. Microcapsules had a mean diameter of 3.138 and 4.929 MUm without drug, and of 4.680 and 5.182 MUm with drug using USP and 8003 pectin, respectively. The in vitro release of acetaminophen from microcapsules was slow and the drug release mechanism was controlled by diffusion following first-order kinetics. There was greater release of acetaminophen in simulated gastric fluid than simulated intestinal fluid conditions. Concluding, the polymeric system present herein seemed to be appropriate for a prolonged release of acetaminophen throughout the gastrointestinal tract. Nevertheless, it is likely that it is a promising pectin/casein complex for lipossoluble drugs, which merits further investigation. PMID- 22322382 TI - Tanshinone IIA inhibits BT-20 human breast cancer cell proliferation through increasing caspase 12, GADD153 and phospho-p38 protein expression. AB - Breast cancer is the leading cause of cancer-related deaths in women worldwide. Tanshinone IIA (Tan-IIA) is one of the pure compounds from Salviae miltiorrhizae radix (Danshen). Tan-IIA can inhibit human breast cancer cells but the molecular mechanisms are not well understood. Our previous study showed that Tan-IIA can inhibit hep-J5 human hepatocellular carcinoma cells through the endoplasmic reticulum (ER) stress-induced apoptotic pathway. In the present study, we evaluated the effects of Tan-IIA on BT-20 human breast cancer cells and assessed the involvement of the ER-stress-apoptotic pathway. The cytotoxicity of Tan-IIA in BT-20 cells was measured by the MTT assay. The cell cycles were analyzed by flow cytometry. The expression of ER stress-related proteins in BT-20 cells treated with Tan-IIA were evaluated by western blotting and immunocytochemical staining. These results showed that Tan-IIA can inhibit BT-20 cells and increase the sub-G1 phase in a time- and dose-dependent manner. Tan-IIA could increase the protein expression of caspase 12, GADD153, caspase 3, phospho-JNK, phospho-p38 and Bax, but decreased Bcl-xl and phospho-ERK expression in BT-20 cells. These findings indicate that Tan-IIA possesses therapeutic potential for human breast cancer BT-20 cells; one of the molecular mechanisms may be through inducing ER stress and the MAPK pathway to induce apoptosis and inhibit proliferation. PMID- 22322383 TI - Combined effect of hypothermia and caspase-2 gene deficiency on neonatal hypoxic ischemic brain injury. AB - INTRODUCTION: [corrected] Hypoxia-ischemia (HI) injury in term infants develops with a delay during the recovery phase, opening up a therapeutic window after the insult. Hypothermia is currently an established neuroprotective treatment in newborns with neonatal encephalopathy (NE), saving one in nine infants from developing neurological deficits. Caspase-2 is an initiator caspase, a key enzyme in the route to destruction and, therefore, theoretically a potential target for a pharmaceutical strategy to prevent HI brain damage. METHODS: The aim of this study was to explore the neuroprotective efficacy of hypothermia in combination with caspase-2 gene deficiency using the neonatal Rice-Vannucci model of HI injury in mice. RESULTS: HI brain injury was moderately reduced in caspase-2(-/-) mice as compared with wild-type (WT) mice. Five hours of hypothermia (33 degrees C ) vs. normothermia (36 degrees C) directly after HI provided additive protection overall (temperature P = 0.0004, caspase-2 genotype P = 0.0029), in the hippocampus and thalamus, but not in other gray matter regions or white matter. Delayed hypothermia initiated 2 h after HI in combination with caspase-2 gene deficiency reduced injury in the hippocampus, but not in other brain areas. DISCUSSION: In conclusion, caspase-2 gene deficiency combined with hypothermia provided enhanced neuroprotection as compared with hypothermia alone. PMID- 22322384 TI - Comparison of online single-breath vs. online multiple-breath exhaled nitric oxide in school-age children. AB - INTRODUCTION: Standards for online multiple-breath (mb) exhaled nitric oxide (eNO) measurements and studies comparing them with online single-breath (sb) eNO measurements are lacking, although eNOmb requires less cooperation in children at school age or younger. METHODS: Online eNOmb and eNOsb were measured in 99 healthy children and (in order to observe higher values) in 21 children with suspected asthma at a median age of 6.1 and 11.7 y, respectively. For eNOmb, we aimed for 20 tidal breathing maneuvers; eNOsb was measured according to standards. The two techniques were compared by standard methods after computing NO output or extrapolating eNOmb to the standard flow of 50 ml/s (eNOmb(50)). RESULTS: Measurements were acceptable in 82 (eNOmb) and 81 (eNOsb) children. Paired data were available for 65 children. On a log-log scale, eNOmb(50) (geometric mean +/- SD 13.1 +/- 15.5 parts per billion, ppb) was correlated with eNOsb (12.5 +/- 15.8 ppb), with r(2) = 0.87. The mean difference between eNOsb and eNOmb(50) was -0.7 ppb, with limits of agreement (LOAs) of 4.0 and -5.3 ppb. DISCUSSION: Despite its correlation with eNOsb, the LOA range hampers eNOmb use in research, where exact values across the whole range are warranted. However, eNOmb might be an alternative tool especially at preschool age, when cooperation during measurements is crucial. PMID- 22322385 TI - Bifidobacterium bifidum in a rat model of necrotizing enterocolitis: antimicrobial peptide and protein responses. AB - INTRODUCTION: Necrotizing enterocolitis (NEC) is a devastating disease of premature infants. Probiotics decrease the risk of NEC in clinical and experimental studies. Antimicrobial peptides protect the gut against noxious microbes and shape the commensal microbiota, but their role in NEC remains unclear. METHODS: To investigate the expression of antimicrobial peptides in experimental NEC and the impact of probiotics on their expression, premature rats were divided into three groups: dam fed (DF), hand fed with formula (FF), or hand fed with formula containing Bifidobacterium bifidum (FF + BIF). All groups were exposed to asphyxia and cold stress. RESULTS: Like in human ontogeny, the rat pup has low expression of Paneth cell antimicrobials, which increases rapidly during normal development. The expression of lysozyme, secretory phospholipase A(2) (sPLA(2)), pancreatic-associated proteins 1 and 3 mRNA was elevated in the FF group with a high incidence of NEC, as compared with the DF and FF + BIF groups where the disease was attenuated. DISCUSSION: We conclude that induction of antimicrobial peptides occurs in experimental NEC similar to that reported in human disease and is attenuated when disease is averted by probiotic B. bifidum. The induction of antimicrobial peptides is likely an adaptive mucosal response that is often not sufficient to prevent disease in the premature gut. PMID- 22322386 TI - Height, BMI, and pituitary volume in individuals with and without isolated cleft lip and/or palate. AB - INTRODUCTION: Individuals with isolated cleft lip and/or palate (ICLP) are often reported to be of shorter stature relative to peers, and the objective of this study was to explore the role of the pituitary in relationship to growth. METHODS: Fifty-five males and 32 females with ICLP were compared to 121 healthy males and 158 healthy females with respect to height and BMI. Magnetic resonance imaging (MRI) scans were obtained from all ICLP participants and 47% of healthy group participants. RESULTS: Males with ICLP were shorter than healthy males and had lower BMI. However, the trajectories for height and BMI did not differ between groups. Analyses in a separate sample of adult males suggested that height normalizes in males with ICLP in their early 30s. There were no differences in mean pituitary volume and pituitary trajectories between male groups. Females with ICLP were shorter than healthy females and also had slower growth rates. They did not differ in mean BMI or BMI trajectories. Furthermore, there were no differences in mean pituitary volume, or in pituitary trajectories. DISCUSSION: Our findings suggest that there are no gross morphological differences in pituitary volume in individuals with ICLP, although more subtle differences may exist. PMID- 22322387 TI - Pentoxifylline and prevention of hyperoxia-induced lung -injury in neonatal rats. AB - INTRODUCTION: Oxygen exposure plays an important role in the pathogenesis of bronchopulmonary dysplasia (BPD). The phosphodiesterase inhibitor pentoxifylline (PTX) has anti-inflammatory and antifibrotic effects in multiple organs. It was hypothesized that PTX would have a protective effect on hyperoxia-induced lung injury (HILI). METHODS: Newborn Sprague-Dawley rats were exposed to >95% oxygen (O(2)) and injected subcutaneously with normal saline (NS) or PTX (75 mg/kg) twice a day for 9 d. NS-injected, room air-exposed pups were controls. At days 4 and 9, lung tissue was collected to assess edema, antioxidant enzyme (AOE) activities, and vascular endothelial growth factor (VEGF) expression. At day 9, pulmonary macrophage infiltration, vascularization, and alveolarization were also examined. RESULTS: At day 9, treatment with PTX significantly increased survival from 54% to 88% during hyperoxia. Treatment with PTX significantly decreased lung edema and macrophage infiltration. PTX treatment increased lung AOE activities including those of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). Furthermore, PTX treatment also increased the gene expression of VEGF189 and VEGF165, increased VEGF protein expression, and improved pulmonary vascularization. DISCUSSION: These data indicate that the reduced lung edema and inflammation, increased AOE activities, and improved vascularization may be responsible for the improved survival with PTX during hyperoxia. PTX may be a potential therapy in reducing some of the features of BPD in preterm newborns. PMID- 22322388 TI - Anthelminthic efficacy of banana crop residues on gastrointestinal nematodes of sheep: in vitro and in vivo tests. AB - Resistance to anthelminthics is common due to intensive and incorrect use. In searching for alternatives, extracts of banana plant were evaluated for egg hatching inhibition and fecal egg count reduction of sheep nematodes. Aqueous extracts of the leaf, pseudostem, and heart of the banana plant cv. Prata ana were tested at concentrations of 0.31, 0.62, 1.25, 2.5, 5.0, and 10.0 mg ml(-1) in egg hatching inhibition tests. For in vivo analysis, aqueous extracts were evaluated at dosages calculated according to the 10% lethal dose derived from acute toxicity testing in mice. Efficacy was evaluated at two time periods following oral administration. For the banana extracts at 2.5 mg ml(-1), egg hatching was significantly fewer than the negative control, with an LC(50) and LC(90) of 0.19 and 0.84 mg ml(-1), respectively. In vivo analysis for weeks 1 and 2 following a single treatment with aqueous leaf extract showed 33.1% and 32.5% anthelminthic efficacy, respectively. Further research on higher dosages with more frequent administration is needed to evaluate the potential for utilizing banana plant residues in gastrointestinal nematode control. PMID- 22322389 TI - Freshwater abiotic components' impact on the viability of fish lice, Argulus sp., in Guangdong province, China. AB - Parasite intensity dynamics can be strongly affected by ecosystem abiotic components. We conducted this study to investigate how the intensity of Argulus sp. is influenced by physicochemical factors in three water bodies - river, fish farm, and reservoir - and to find the occurrence of Argulus sp. under different conditions. Argulus sp. specimens were collected using different methods - gill netting 30 * 1.5 m, 40 mm mesh monofilament net and set from a small boat, beach seining and plankton net - from July 2010 until Jun 2011 at Guangdong province, China. Main water parameters taken for the assessment consisting of temperature, pH, DO, biochemical oxygen demand of 5 days (BOD5), chemical oxygen demand (COD), NH (4) (+) , total nitrogen (TN) and total phosphorus (TP). The results show that the ratio of female to male Argulus sp. during the studied period was 2.3:1. The presence and intensity of Argulus sp. were temperature-dependent and variable; pH values were lower than standers with high intensity of Argulus sp. Argulus sp. has the ability to live in low dissolved oxygen (DO) concentration. Relatively high concentrations of BOD5, COD, NH (4) (+) , TN and TP were detected with related variable intensity of Argulus sp., which is supposed to be a freshwater fish ectoparasite found in polluted ecosystems. It is concluded that the fish ectoparasite Argulus sp. have a strong potency of genetic adaptation impacted by environmental factors. However, this needs further study in order to gain insight into the question of the likelihood of adaptation to abiotic factors' variation. PMID- 22322390 TI - The ileal neobladder in female patients with bladder cancer: long-term clinical, functional, and oncological outcome. AB - PURPOSE: To assess long-term clinical and oncological outcome in women undergoing radical cystectomy and ileal neobladder reconstruction for invasive bladder cancer. METHODS: From 1995 to 2010, a total of 121 women with clinically organ confined urothelial carcinoma underwent radical cystectomy with an orthotopic ileal neobladder. Median follow-up was 56 months. Clinical course, functional, pathological, and oncological outcome of these women were analyzed. RESULTS: Seventy-six patients (62.8%) experienced a complication of some type within 90 days of the procedure. 56 patients (46.3%) experienced minor complications, whereas 20 patients (16.5%) experienced major complications. Pathological subgroups included 70 patients (57.9%) with organ confined, lymph node-negative tumors, 24 (19.8%) with extravesical, lymph node-negative disease and 27 (22.3%) patients with lymph node-positive disease. The 5-year overall survival rate in patients with organ-confined (<=pT2, pN0), locally advanced (>=pT3, pN0), and metastatic disease was 80.2%, 81.9%, and 45.1%, respectively. 4 women (3.3%) experienced a local (pelvic) recurrence. One patient presented with a urethral recurrence (0.8%). Daytime and nighttime urinary continence (0-1 pad) was reported by 82.4 and 76.5%, respectively. Clean intermittent self-catheterization was required by 58.0%. The retrospective study design was the major limitation of the study. CONCLUSIONS: Despite a considerable complication rate, radical cystectomy with orthotopic diversion in female patients with bladder cancer may be considered a standard therapeutic option for selected patients with excellent oncological outcome including a low incidence of local and urethral recurrence. PMID- 22322391 TI - 3D-RISM-KH molecular theory of solvation and density functional theory investigation of the role of water in the aggregation of model asphaltenes. AB - We applied a multiscale modeling approach that involves the statistical mechanical three-dimensional reference interaction site model with the Kovalenko Hirata closure approximation (3D-RISM-KH molecular theory of solvation) as well as density functional theory (DFT) of electronic structure to study the role of water in aggregation of the asphaltene model compound 4,4'-bis(2-pyren-1-yl ethyl)-2,2'-bipyridine (PBP) [X. Tan, H. Fenniri and M. R. Gray, Energy Fuels, 2008, 22, 715]. The solvation free energy and potential of mean force predicted by 3D-RISM-KH reveal favorable pathways for disaggregation of PBP dimers in pure versus water-saturated chloroform solvent. The water density distribution functions elucidate hydrogen bonding preferences and water bridge formation between PBP monomers. The DeltaG(298) values of -5 to -7 kcal mol(-1) for transfer of water molecules in chloroform to a state interacting with PBP molecules are in agreement with experimental results. Geometry optimization and thermochemistry analysis of PBP dimers with and without water bridges using WB97Xd/6-31G(d,p) predict that both PBP dimerization and dimer stabilization by water bridges are spontaneous (DeltaG(298) < 0). The (1)H NMR chemical shifts of PBP monomers and dimers predicted using the gauge-independent atomic orbital method and polarizable continuum model for solvation in chloroform are in an excellent agreement with the experimental results for dilute and concentrated PBP solutions in chloroform, respectively [X. Tan, H. Fenniri and M. R. Gray, Energy Fuels, 2009, 23, 3687]. The DFT calculations of PBP dimers with explicit water show that bridges containing 1-3 water molecules lead to stabilization of PBP dimers. Additional water molecules form hydrogen bonds with these bridges and de shield the PBP protons, negating the effect of water on the (1)H(C3) NMR chemical shift of PBP, in agreement with experiment. The DeltaG(298) results show that hydrogen bonding to water and water-promoted polynuclear assembly bridging is as important as pi-pi interactions for asphaltene aggregation. PMID- 22322392 TI - Function and morphology in macular retinoschisis associated with optic disc pit in a child before and after its spontaneous resolution. AB - Optic disc pit (ODP) is a rare congenital defect within the optic nerve head. Macula elevation associated with ODP develops in 75-93% of the adult patients. Macular involvement in children with optic disc pit is rare, and only a few cases have been published to date. In the present case, we have observed morphology and function of the central retina in a child with ODP-associated macular detachment and following its spontaneous resolution. An 8-year-old white boy diagnosed with a macular detachment in an eye with an ODP. Optical coherent tomography (OCT) and multifocal electroretinography (mfERG), as well as visual acuity and visual field, were performed in the follow-up of the unilateral schisis-like retinal detachment. A large retinoschisis associated with ODP in a child showed a tendency to spontaneously resolve at 3 months, which was confirmed on OCT. At this time, an mfERG revealed markedly reduced responses. Despite morphologic reattachment at follow-up and improvement in visual acuity, increased mfERG responses were still not the same as in the fellow healthy eye. In contrast to the OCT which is very helpful to assess the extent of the neurosensory detachment, the mfERG offers an additional tool for follow-up of retinal function in this disorder. The good visual outcome in our patient shows that in the presence of residual retinal function on mfERG and in the absence of further lesions on OCT, follow-up is a valid option in children with an ODP-associated macular detachment. PMID- 22322393 TI - Oral mucosa response to laser patterned microcoagulation (LPM) treatment. An animal study. AB - In this study a minimally invasive microsurgical approach was used for laser patterned microcoagulation (LPM) to initiate gingival and oral mucosal tissue regeneration. We performed a feasibility assessment and histological examination of laser damage and regeneration in the gingiva and oral mucosa using an animal model. The study animals comprised 18 healthy rabbits which were treated in vivo with single pulses from a diode laser at a wavelength of 980 nm and a power of up to 20 W applied to the gingival and oral mucosa at multiple time points. Biopsies were stained with hematoxylin and eosin, nitroblue tetrazolium chloride and picrosirius red, and evaluated by two pathologists blinded to the parameters and date of laser exposure. Histological analysis revealed that the continuity of the epithelial basal cell layer had been reestablished by 1-2 days after LPM, and complete epithelial regeneration had occurred by 7-12 days. A pronounced reactive inflammation developed in the column area 1 day after treatment. High activity of fibroblasts producing new collagen participated in the formation of a network of new thin-wall blood vessel. By the 28th day the tissue structure was almost completely restored with a similar increase of vascularity, and there were no signs of scarring. By the 90th day, tissue structure was completely restored, indicating complete healing. A single LPM treatment induces a wound healing response in the oral mucosa, showing the potential of LPM for the initiation of oral mucosa and gingival regeneration. Complete healing observed in 3 months after treatment with no keratinization change or scar tissue formation. PMID- 22322394 TI - Isolation, structural elucidation, and cytotoxicity of three new ent-kaurane diterpenoids from Isodon japonica var. glaucocalyx. AB - Three new ENT-kaurane diterpenoids, glaucocalyxin H ( 1), glaucocalyxin I ( 2), and glaucocalyxin J ( 3), together with four known diterpenoids ( 4- 7), were isolated from the leaves of Isodon japonica Hara var. glaucocalyx. Their structures were elucidated by spectroscopic analysis, and the structures of compounds 2 and 3 were further confirmed by X-ray crystallographic analysis. Compounds 1, 4, and 5 were evaluated for their cytotoxicity IN VITRO against CE 1, U87, A-549, MCF-7, Hela, K-562, and HepG-2 human tumor cell lines. Compound 1 showed potent inhibitory activities against six tumor cell lines with IC (50) values ranging from 1.86-10.95 uM, and compounds 4 and 5 exhibited significant selective cytotoxicity on seven tumor cell lines. PMID- 22322395 TI - Plant exposures reported to the Poisons Information Centre Erfurt from 2001-2010. AB - At the moment, no recent study about plant exposures in Germany and in the federal states the Poisons Information Centre (PIC) Erfurt is serving is available. To get new information about important characteristics of plant exposures like the development of frequency, plants, age groups involved, circumstances of exposure, and symptom severity, we conducted a retrospective study including all human plant exposures reported to the PIC Erfurt over a 10 year period from the beginning of 2001 to the end of 2010. In total, 13 001 plant exposures were registered. While the absolute number of plant exposures discontinuously increased from 1110 in 2001 to 1467 in 2009, and decreased to 1157 in 2010, their relative frequency to all human exposures fell from 9.2 % in 2001 to 5.9 % in 2010. Age groups: children 87.5 % (toddler 60.0 %); adults 11.3 % (middle-aged adults 5.2 %). Gender: female 39.0 % and male 41.2 %. Circumstances: accidental 91.6 %, unknown 4.6 %, abuse 2.9 %, suicide 0.9 %. Severity of symptoms: none to slight 85.5 %, moderate 1.7 %, unknown 12.7 %, severe 0.1 % (in total 9, one 4-year-old girl, involved plant genera: Aconitum, Arum, Chelidonium, Datura, brugmansia, Dieffenbachia, Ricinus, 2 Taxus), fatal 0.03 % (in total 4, involved plant genera: 2 Aconitum, 2 Taxus). In comparison to all human exposures, the relative frequency of severe symptoms in accidental and intentional plant exposures by abuse was significantly lower but as high by suicide. The significant higher involvement of children resulted mainly in none or mild symptoms. Severe symptoms could mostly be observed in adults in intentional plant exposures or when poisonous plants were mistaken for eatable. Because some plant exposures resulted in severe symptoms and even death, their dangerousness should not be trivialised. PMID- 22322396 TI - Pharmacokinetic herb-drug interactions (part 1): origins, mechanisms, and the impact of botanical dietary supplements. AB - Phytochemicals have been components of man's diet for millennia and are believed to have played a significant role in steering the functional development of xenobiotic metabolizing enzymes and transporters within the human gastrointestinal tract. Only recently, however, have plant secondary metabolites been recognized as modulators of human drug disposition. Despite exposure to thousands of structurally diverse dietary phytochemicals, only a few appear to significantly modulate human drug metabolizing enzymes and transporters. In some instances, these interactions may have beneficial effects like cancer prevention, whereas others may dramatically affect the pharmacokinetics of concomitantly administered drugs. In today's global economy, the opportunity for exposure to more exotic phytochemicals is significantly enhanced. Formulated as concentrated phytochemical extracts, botanical dietary supplements are vehicles for a host of plant secondary metabolites rarely encountered in the normal diet. When taken with conventional medications, botanical dietary supplements may give rise to clinically significant herb-drug interactions. These interactions stem from phytochemical-mediated induction and/or inhibition of human drug metabolizing enzymes and transporters. PMID- 22322397 TI - Three new cycloartenol glycosides from the roots of Cimicifuga simplex. AB - Three new cycloartenol triterpene saponins, 3 beta,16 alpha-dihydroxy-12-acetoxy 16,22-cyclo-23-ketone-24 R,25-epoxy-cycloartane-7-ene 3- O- beta-D galactopyranoside ( 1), 24- O-hydroxy-7,8-didehydrohydroshengmanol 3- O- beta-D galactopyranoside ( 2), and 24-epi-24- O-hydroxy-7,8-didehydrohydroshengmanol 3- O- beta-D-galactopyranoside ( 3), were isolated from the ethyl acetate soluble fraction of Cimicifuga simplex. Their structures were established by detailed spectroscopic analysis, including extensive 2D-NMR data. This is the first time that a 16,22-cyclo type glycosidesaponin from aCimicifuga species was reported. The immunosuppressive activities of the new compounds were evaluated by a ConA stimulated T splenocyte proliferation assay in vitro. PMID- 22322398 TI - Metabolite profiling of the leaves of the Brazilian folk medicine Sideroxylon obtusifolium. AB - Sideroxylon obtusifolium (Roem. & Schult.) T. D. Penn. (family Sapotaceae) is a tree native to Central and South America. Infusions of the bark and the leaves are used in Brazilian folk medicine as an anti-inflammatory remedy. However, information on the constituents of S. obtusifolium remains scarce, and only common pentacyclic triterpenoids have been previously reported. HPLC-DAD/MS analyses revealed that saponins and flavonoids were the main constituents of the leaves. From the butanol-soluble fraction of an ethanolic extract, a total of four saponins and ten flavonol glycosides were isolated by a combination of chromatographic methods including Sephadex LH-20, MPLC, and HPLC. Their structures were established by acid hydrolysis and spectroscopic methods, mainly MS (n), 1D and 2D NMR experiments. The compounds include the new triterpene glycoside 3-O-( beta-D-glucopyranosyl)-protobassic acid 28-O- beta-D apiofuranosyl-(1 -> 3)-O-[O- beta-D-apiofuranosyl-(1 -> 3)- beta-D-xylopyranosyl (1 -> 4)]-O- alpha-L-rhamnopyranosyl-(1 -> 2)- alpha-L-arabinopyranosyl ester ( 1), as well as the new flavonol glycosides, quercetin-3-O-(O- alpha-L rhamnopyranosyl-(1-> 2)-O-[ beta-D-glucopyranosyl-(1 -> 3)]- beta-D galactopyranoside) ( 6) and kaempferol-3-O-(O- alpha-L-rhamnopyranosyl-(1 -> 2)-O [ beta-D-glucopyranosyl-(1 -> 3)]- beta-D-galactopyranoside) ( 8). In addition, catechin and a glycerogalactolipid, gingerglycolipid A, were obtained from the ethyl acetate-soluble fraction. The isolated compounds could be used in the future as chemical markers for quality control of this herbal drug. PMID- 22322399 TI - Can amorphization take place in nanoscale interconnects? AB - The trend of miniaturization has highlighted the problems of heat dissipation and electromigration in nanoelectronic device interconnects, but not amorphization. While amorphization is known to be a high pressure and/or temperature phenomenon, we argue that defect density is the key factor, while temperature and pressure are only the means. For nanoscale interconnects carrying modest current density, large vacancy concentrations may be generated without the necessity of high temperature or pressure due to the large fraction of grain boundaries and triple points. To investigate this hypothesis, we performed in situ transmission electron microscope (TEM) experiments on 200 nm thick (80 nm average grain size) aluminum specimens. Electron diffraction patterns indicate partial amorphization at modest current density of about 10(5) A cm(-2), which is too low to trigger electromigration. Since amorphization results in drastic decrease in mechanical ductility as well as electrical and thermal conductivity, further increase in current density to about 7 * 10(5) A cm(-2) resulted in brittle fracture failure. Our molecular dynamics (MD) simulations predict the formation of amorphous regions in response to large mechanical stresses (due to nanoscale grain size) and excess vacancies at the cathode side of the thin films. The findings of this study suggest that amorphization can precede electromigration and thereby play a vital role in the reliability of micro/nanoelectronic devices. PMID- 22322400 TI - Proximate and fatty acid composition of some commercially important fish species from the Sinop region of the Black Sea. AB - The proximate and fatty acid compositions of the commercially important fish species (Engraulis encrasicolus, Alosa alosa, Belone belone, Scorpaena porcus, Pomatomus saltatrix, Mullus barbatus) from the Sinop region of the Black Sea were examined. The fat contents ranged from 1.26% (for scorpion fish) to 18.12% (for shad). The protein contents were min 14.54% (for red mullet) and maximum 20.26% (for belone). The fatty acid compositions of the fish ranged from 27.83 to 35.91% for saturated fatty acids, 19.50-33.80% for monounsaturated fatty acids and 15.25 40.02% for polyunsaturated fatty acids. Among the saturated fatty acids, palmitic acid (16:0) (17.75-22.20%) was the dominant fatty acid for all the fish species. As a second saturated fatty acid, myristic acid (14:0) was observed in four of the fish species and its content ranged from 4.72 to 7.31%. Whereas, for the other two fish species, the second saturated fatty acid was stearic acid (18:0) ranging between 4.54 and 10.64%. Among the monounsaturated fatty acids, those occurring in the highest proportions were oleic acid (18:1n-9c) (11.67-22.45%) and palmitoleic acid (16:1) (4.50-9.40%). Docosahexaenoic acid (22:6n-3) (5.41 28.52%), eicosapentaenoic acid (20:5n-3) (4.68-11.06) and linoleic acid (18:2n-6) (1.38-3.49%) were dominant polyunsaturated fatty acids, respectively. All the species, in particular the belone, the anchovy and the shad had high levels of the n-3 series. PMID- 22322401 TI - A case series of concomitant treatment of perhexiline with amiodarone. AB - BACKGROUND: Concomitant treatment with amiodarone and perhsexiline has been considered to be relatively contraindicated because of the hypothetical risk of potentiated adverse effects mediated by additive inhibition of carnitine palmitoyl transferase 1. AIM: To study the prevalence of adverse effects associated with the concomitant use of perhexiline and amiodarone. METHODS: A retrospective analysis of a single hospital database of patients receiving perhexiline and amiodarone between July 2009 and April 2011. Files were reviewed for short- and long-term adverse effects requiring drug cessation. Glucose concentration, gamma glutamyl transferase activity. and perhexiline blood concentrations were recorded. RESULTS: We identified 26 patients concomitantly treated with perhexiline and amiodarone, 20 on a long-term basis. In 6 cases, amiodarone was introduced on top of preceding perhexiline. In none of the cases were drugs stopped because of adverse effects. Although blood glucose concentrations fell significantly 48 hours postadmission to hospital, this seems to reflect the resolution of "admission hyperglycemia" rather than onset of hypoglycemia; the latter was rare (5 patients), mild, and clinically silent. In 4 patients, gamma glutamyl transferase approximately doubled. CONCLUSIONS: Traditionally, concomitant treatment with amiodarone and perhexiline has been considered to be relatively contraindicated on the basis of the theoretical potential for synergistic toxicity. This cohort of 26 patients received this concomitant treatment without any excess of major adverse reactions. Our findings suggest that concomitant treatment with perhexiline and amiodarone may be safe in the setting of (1) previous tolerance of either agent, and (2) titration of plasma perhexiline concentrations to guide therapy. PMID- 22322402 TI - Analytical performance of a new liquid chromatography/tandem mass spectrometric method for determination of everolimus concentrations in whole blood. AB - The immunosuppressant everolimus was recently approved for prophylactic use in the United States, to prevent organ rejection in adult kidney transplant recipients. The currently accepted therapeutic range for everolimus is 3-8 ng/mL. Therapeutic drug monitoring (TDM) using predose EDTA whole blood samples is required to optimize dose. We describe a simple extraction method and analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS) to support routine TDM of everolimus. Samples were prepared by protein precipitation and filtration. The first quadrupole was set to select the ammonium adducts (Equation is included in full-text article.)of everolimus (m/z 975.62) and rapamycin-d3 (m/z 934.70), the internal standard. The second quadrupole was used as a collision chamber, and the third quadrupole was then used to select characteristic product ions of everolimus (m/z 908.50 and 890.50) and rapamycin-d3 (m/z 864.60 and 846.50). The method had an analytical measurement range of 2.0-150 ng/mL. Total imprecision, expressed as percent coefficient of variation (mean concentration), was 19.1% (3.3 ng/mL), 10.6% (5.9 ng/mL), 8.1% (19.2 ng/mL), 5.7% (25.8 ng/mL), and 9.1% (34.2 ng/mL). The new method was compared with 2 other everolimus methods also based on LC-MS/MS, with 64 residual patient specimens. Agreement, based on simple linear regression, was excellent. Method A comparison: y = 0.96x - 1.12 (r = 0.99), n = 20, 2.5-44.7 ng/mL. Method B comparison: y = 0.96x + 0.49 (r = 0.99), n = 44, 2.1-85.6 ng/mL. We conclude that this method could support TDM of everolimus for a wide range of clinical indications. PMID- 22322403 TI - miR-21 promotes migration and invasion by the miR-21-PDCD4-AP-1 feedback loop in human hepatocellular carcinoma. AB - Distant migration and invasion is the main contributor to the death of cancer patients and miRNAs have been implicated in these processes. In the present study, we identified the role of microRNA-21 (miR-21) in hepatocellular carcinoma (HCC) migration and invasion and determined its underlying regulatory mechanism. miR-21 was significantly upregulated in HCC tissues and cell lines, compared with adjacent non-tumor tissues and normal hepatic cells. miR-21 upregulation was associated with the capacity of tumor migration and invasion in HCC. The expression level of miR-21 was inversely correlated with the protein expression level of a previously identified target gene, programmed cell death 4 (PDCD4). In HepG2 cells, inhibition of miR-21 expression repressed cell migration and invasion by upregulating both mRNA and protein levels of PDCD4 and downregulating key downstream signaling pathway molecules, including phospho-c-Jun, matrix metalloproteinases (MMP)-2 and MMP-9. Moreover, activation protein 1 (AP-1) could directly activate miR-21 transcription. Taken together, these results provide evidence that miR-21 promotes migration and invasion in HCC through the miR-21 PDCD4-AP-1 feedback loop, suggesting that targeting the miR-21-PDCD4-AP-1 loop may represent a promising strategy in the management of HCC. PMID- 22322404 TI - Interactions in different domains of truxenone supramolecular assembly on Au(111). AB - The two-dimensional assemblies of truxenone, diindeno[1,2-a;1',2'-c]fluorene 5,10,15-trione, on the Au(111) surface have been studied by scanning tunnelling microscopy in ultrahigh vacuum. It is found that the truxenone monolayer on Au(111) exhibits different two-dimensional supramolecular structures. The investigation using scanning tunnelling microscopy combined with the density functional theory calculations can be a helpful approach to understand the complicated supramolecular structures of truxenone self-assembly on Au(111). PMID- 22322405 TI - First study on anthropogenic Pt, Pd, and Rh levels in soils from major avenues of Sao Paulo City, Brazil. AB - Over the last years, investigations on the increase of platinum (Pt), palladium (Pd), and rhodium (Rh) levels in urban environments of big cities all over the world - especially to catalytic converters emissions - have been grown up enormously. Sao Paulo City is the 6th largest megacity in the world having about 20 million inhabitants and an ever increasing seven million motor vehicle fleet. In spite of this, there has never been an investigation regarding Pt, Pd, and Rh levels in the city. In the present study, Pt, Pd, and Rh concentrations were determined in soils adjacent to seven main high-density traffic avenues in the metropolitan region of Sao Paulo City. Inductively coupled plasma mass spectrometry was employed - after ultrasound-assisted aqua regia leaching - as analytical technigue. The results showed concentration levels up to 378 ng g(-1) for Pd, 208 ng g(-1) for Pt, and 0.2 to 45 ng g(-1) for Rh. These levels are much higher than those considered for the geochemical background of soils, indicating a catalytic converter source. Due to the different Pt/Pd/Rh ratio in Brazilian automobile catalytic converters, lower levels of Pt/Pd ratios compared with other similar studies were observed. The obtained results are the first data for monitoring Pt, Pd, and Rh pollution in Sao Paulo City soils. PMID- 22322406 TI - Assessment of indoor airborne contamination in a wastewater treatment plant. AB - The main objective of this work was to quantify and characterize the major indoor air contaminants present in different stages of a municipal WWTP, including microorganisms (bacteria and fungi), carbon dioxide, carbon monoxide, hydrogen sulfide ammonia, formaldehyde, and volatile organic compounds (VOCs). In general, the total bacteria concentration was found to vary from 60 to >52,560 colony forming units (CFU)/m(3), and the total fungi concentration ranged from 369 to 14,068 CFU/m(3). Generally, Gram-positive bacteria were observed in higher number than Gram-negative bacteria. CO(2) concentration ranged from 251 to 9,710 ppm, and CO concentration was either not detected or presented a level of 1 ppm. H(2)S concentration ranged from 0.1 to 6.0 ppm. NH(3) concentration was <2 ppm in most samples. Formaldehyde was <0.01 ppm at all sampling sites. The total VOC concentration ranged from 36 to 1,724 MUg/m(3). Among the VOCs, toluene presented the highest concentration. Results point to indoor/outdoor ratios higher than one. In general, the highest levels of airborne contaminants were detected at the primary treatment (SEDIPAC 3D), secondary sedimentation, and sludge dehydration. At most sampling sites, the concentrations of airborne contaminants were below the occupational exposure limits (OELs) for all the campaigns. However, a few contaminants were above OELs in some sampling sites. PMID- 22322407 TI - Investigation into organic phosphorus species in sediments of Baiyangdian Lake in China measured by fractionation and 31P NMR. AB - Organic phosphorus (OP) species in sediments of the Baiyangdian Lake in China was investigated via fractionation and phosphorus-31 nuclear magnetic resonance ((31)P NMR) spectroscopy. Results of chemical fractionation showed that different OP fractions ranked in the order: humic acid-P > HCl-OP > fulvic acid-P ~ NaHCO(3)-OP > residual OP. Labile OP and moderately labile OP, which can be degraded for phytoplankton uptake, contributed to 58.7-68.5% of total extracted OP, indicative of the potential P release from sediments in the lake. (31)P NMR spectroscopy results suggested the rank order of P species present in the NaOH EDTA extractant of the sediments: orthophosphate > monoester-P > DNA-P > pyrophosphate-P. Phytate, polyphosphates, and phosphonates, which appeared in sediments of some deeper lakes, were not detected in the shallow lake. Significant correlations were identified between total P (TP) in water column and sediment TP, monoester-P and DNA-P, positively indicating that sediment P species, especially OP components, should probably contribute to the contents of P in water column and further to the lake eutrophication. PMID- 22322408 TI - Estimating soil temperature using neighboring station data via multi-nonlinear regression and artificial neural network models. AB - The aim of this study is to estimate the soil temperatures of a target station using only the soil temperatures of neighboring stations without any consideration of the other variables or parameters related to soil properties. For this aim, the soil temperatures were measured at depths of 5, 10, 20, 50, and 100 cm below the earth surface at eight measuring stations in Turkey. Firstly, the multiple nonlinear regression analysis was performed with the "Enter" method to determine the relationship between the values of target station and neighboring stations. Then, the stepwise regression analysis was applied to determine the best independent variables. Finally, an artificial neural network (ANN) model was developed to estimate the soil temperature of a target station. According to the derived results for the training data set, the mean absolute percentage error and correlation coefficient ranged from 1.45% to 3.11% and from 0.9979 to 0.9986, respectively, while corresponding ranges of 1.685-3.65% and 0.9988-0.9991, respectively, were obtained based on the testing data set. The obtained results show that the developed ANN model provides a simple and accurate prediction to determine the soil temperature. In addition, the missing data at the target station could be determined within a high degree of accuracy. PMID- 22322409 TI - Impact of a phone follow-up program on persistence with teriparatide or PTH(1-84) treatment. AB - A follow-up program to help patients suffering from severe osteoporosis during their therapy with teriparatide or PTH(1-84) has been designed and performed. The objective of this study was to evaluate the 18-month persistence on these therapies in patients participating in the program. We enrolled 382 patients who started teriparatide or PTH(1-84) following this program and compared them with a historical cohort of 398 patients treated with the same therapies but who did not participate in any follow-up program. At the beginning of the therapy, nurses trained patients on self-injection. Patients received one phone call per week during the first month, then one phone call per month and per 3 months during the following 5 and 12 months, respectively. In every call, nurses helped patients to resolve any possible issues and collected adverse event information. The persistence rate of the group following the program was 85.6%, 8.2% higher than that of the group not following any program (77.4%). The log-rank test on persistence rates on therapy in patients enrolled and not enrolled in the program was performed; the difference was statistically significant (P = 0.006). Discontinuation in the follow-up program group occurred mainly at early stages of the treatment due to adverse events. Our results show that patients suffering from severe osteoporosis treated with teriparatide or PTH(1-84) and enrolled in a follow-up program have higher persistence rates than patients not following the program. PMID- 22322410 TI - Differentiation of isomeric amino acid residues in proteins and peptides using mass spectrometry. AB - Characterization and differentiation of isomers in biological macromolecules using mass spectrometry is one of the most significant challenges facing scientists in the field. The capability of high-resolution MS instruments along with the development of new fragmentation methods now provides the ability to indirectly differentiate between some isomers. This ability has enabled mass spectrometry to evolve into a multidisciplinary technique incorporating areas such as pharmaceutical research, proteomics, polymer science, medicine, environmental chemistry, and recently archeology. This article aims to review recent developments in mass spectrometry methodologies in the identification of structural and spatial isomers in biological macromolecules, such as aspartic acid and isoaspartic acid (Asp/IsoAsp), leucine and isoleucine (Leu/Ile), glutamic acid and gamma-glutamic acid, and D/L enantiomers. PMID- 22322411 TI - Antiepileptic drug monotherapy versus polytherapy: pursuing seizure freedom and tolerability in adults. AB - PURPOSE OF REVIEW: Despite the availability of many new antiepileptic drugs (AEDs), only around 50% of people with epilepsy will become seizure free on their first drug. This article explores treatment options and issues influencing whether AEDs should be substituted or combined in the remainder of the patient population. RECENT FINDINGS: Prior to the introduction of novel AEDs, it was generally opined that combining traditional agents did not necessarily lead to an improvement in seizure control and might increase the propensity for side effects. Newer AEDs, many with different mechanisms of action, have increased the potential for polytherapy regimens, although robust data to support or refute this therapeutic strategy are sparse. It seems sensible to substitute rather than combine when the first AED produces an idiosyncratic reaction, is poorly tolerated at a low/moderate dose or shows no efficacy. Polytherapy may be preferred if the patient tolerates their first or second AED well, but with a suboptimal response, particularly when there is an identifiable anatomical substrate for the seizures. AED selection requires consideration of many factors some of which are discussed in this study. SUMMARY: There are no definitive answers on whether to combine or substitute AEDs. Different strategies are required for different scenarios in different patients. PMID- 22322412 TI - Epilepsy surgery utilization: who, when, where, and why? AB - PURPOSE OF REVIEW: Using the most recent evidence, we provide an update on epilepsy surgery, focusing on its effectiveness, reasons for underutilization, considerations of candidacy and timing for referral for epilepsy surgery evaluation. RECENT FINDINGS: The course of illness of epilepsy is being characterized. Well conducted studies describe the patterns of seizure remission and relapse with medical therapy and also in response to epilepsy surgery. Epilepsy surgery is highly effective in selected patients with drug-resistant epilepsy (DRE). The risk-benefit of epilepsy surgery is well known and consistent around the world. However, epilepsy surgery remains underutilized. A randomized controlled trial and Clinical Practice Guidelines (CPGs) supporting epilepsy surgery have had no discernible impact on referral rates for epilepsy surgery evaluation. Criteria and guidelines are being developed for identifying patients who need to be referred for epilepsy surgery evaluation. Quality indicators for epilepsy care now also include the need to consider surgical candidacy every 3 years in DRE. New developments in imaging and neurophysiology promise to help clinicians identify and treat patients more accurately. SUMMARY: Surgery is effective but underused. Comprehensive interventions to translate evidence to practice in epilepsy surgery are urgently needed. PMID- 22322413 TI - Epilepsy care challenges in developing countries. AB - PURPOSE OF REVIEW: This review discusses recent literature relevant to the diagnosis and treatment of epilepsy in developing countries with particular attention to underlying causes, natural history, and advances made toward optimizing systems of care and bridging the treatment gap. RECENT FINDINGS: Prospective data suggest that cerebral malaria-induced brain injury may explain the high prevalence of epilepsy in malaria-endemic regions. Population-based mortality studies support the long proposed hypothesis that seizure-related deaths contribute to excessive premature mortality. WHO guidelines have the potential to improve care, but macrolevel barriers related to pharmaceutical regulation and distribution continue to contribute to the treatment gap. Evidence based guidelines endorsed by the WHO and American Academy of Neurology regarding the optimal management of comorbid epilepsy and HIV may raise awareness regarding critical drug interactions between antiepileptic drugs and antiretrovirals, but are also problematic as the treatment regimen and diagnostic facilities routinely available in developing countries will prevent most healthcare providers from following the recommendations. SUMMARY: New insights into the causes, natural history and best care practices for epilepsy in developing countries are available but without prioritization and action from policy makers, the present treatment gap will likely to persist. PMID- 22322414 TI - Functional imaging of seizures and epilepsy: evolution from zones to networks. AB - PURPOSE OF REVIEW: Epilepsy research has extended from studies at the cellular level to the investigation of interactions of large neuronal populations distant from one another: 'epileptic networks'. This article underlines the concept of epilepsies as network disorders, adding empirical evidence from electroencephalography-combined functional MRI (EEG-fMRI) studies. RECENT FINDINGS: These noninvasive in-vivo EEG-fMRI epilepsy studies have characterized the ictal temporal-spatial evolution and the interictal persistence of altered activity in typical sets of (sub)cortical brain regions responsible for the clinical manifestation of the disease and its underlying encephalopathy, for example, thalamus vs. cortex in generalized; hippocampus vs. cortex in temporal lobe; a frontal near-piriform region universally in focal epilepsies. Models exist validated against intracranial EEG that can explain interictal and ictal activity based on statistical coupling between different brain regions, and if extended could guide the design of new treatments. SUMMARY: The appreciation of epileptic processes at the network level will foster the development of both anticonvulsive as well as true antiepileptic treatment strategies locally modulating hub regions within the epileptic network architecture as well as entire networks by targeting their characteristic properties such as neurotransmitter or neuronal firing profiles. Treatment should reach beyond seizure control and include the improvement of cognitive function. PMID- 22322415 TI - Ketogenic diets: new advances for metabolism-based therapies. AB - PURPOSE OF REVIEW: Despite myriad anticonvulsants available and in various stages of development, there are thousands of children and adults with epilepsy worldwide still refractory to treatment and not candidates for epilepsy surgery. Many of these patients will now turn to dietary therapies such as the ketogenic diet, medium-chain triglyceride diet, modified Atkins diet, and low glycemic index treatment. RECENT FINDINGS: In the past several years, neurologists are finding new indications to use these dietary treatments, perhaps even as first line therapy, including infantile spasms, myoclonic-astatic epilepsy (Doose syndrome), Dravet syndrome, and status epilepticus (including FIRES syndrome). Adults are also one of the most rapidly growing populations being treated nowadays; this group of patients previously was not typically offered these treatments. In 2009, two controlled trials of the ketogenic diet were published, as well as an International Expert Consensus Statement on dietary treatment of epilepsy. Ketogenic diets are also now being increasingly studied for neurological conditions other than epilepsy, including Alzheimer's disease and cancer. Insights from basic science research have helped elucidate the mechanisms by which metabolism-based therapy may be helpful, in terms of both an anticonvulsant and possibly a neuroprotective effect. SUMMARY: Dietary therapy for epilepsy continues to grow in popularity worldwide, with expanding use for adults and conditions other than epilepsy. PMID- 22322416 TI - Turner syndrome: advances in understanding altered cognition, brain structure and function. AB - PURPOSE OF REVIEW: Turner syndrome, which results from the complete or partial loss of a sex chromosome, is associated with a particular pattern of cognitive impairments and strengths and an increased risk for specific neurodevelopmental disorders. This review highlights recent progress in understanding brain structure and function in Turner syndrome and identifies several critical research needs. RECENT FINDINGS: Recent work on social cognition in Turner syndrome has identified a range of difficulties despite a maintained social appetite, a disconnect which could result in distress for affected individuals. Progress has been made in identifying foundational deficits in attention and executive function that could explain visual-spatial and arithmetical impairments. Neuroimaging studies have advanced our understanding of brain development and function through the application of cutting edge analysis techniques. Haploinsufficiency of genes, failure to express parentally imprinted genes, uncovering of X chromosome mutations, and gonadal steroid deficiency may all contribute to altered brain development, but additional work is required to link specific mechanisms to specific phenotypes. Also needed are studies of interventions to assist individuals with Turner syndrome in visual-spatial, mathematical, and social skills. SUMMARY: Ultimately a better understanding of brain structure and function in Turner syndrome will generate new therapeutic approaches for this population. PMID- 22322417 TI - Perspectives on the dynamic development of cognitive capacities: insights from Williams syndrome. AB - PURPOSE OF REVIEW: This article identifies an increasing change from rather static approaches to neurodevelopmental disorders and the search for 'intact' and 'impaired' domain-specific modules, to more recent dynamic perspectives that take account of cross-domain interactions and changes over developmental time. RECENT FINDINGS: Research on Williams syndrome is taken as a model, used to demonstrate the static versus dynamic perspectives, covering new work on social cognition, spatial cognition, and sleep-related consolidation of memory in neurodevelopmental disorders, as well as hypothesis-driven cross-syndrome comparisons. Many previously considered 'intact' domains have now been shown to harbour subtle deficits because of the cross-domain interactions typical of early periods of infant development. Sleep architecture has been found to be atypical in all syndromes hitherto assessed, with consequent impact on learning. This has opened avenues for sleep intervention which may impact on subsequent cognitive development. SUMMARY: Cross-syndrome associations, and not merely cross-syndrome dissociations or comparisons with typical development, are shown to be particularly relevant for advancing theory and research. These comparisons reveal that clinical intervention strategies should aim at syndrome-specific remediation as early in the developmental trajectory as possible. PMID- 22322418 TI - Learning from chromosomal disorders: progress and prospects. PMID- 22322419 TI - Autologous transplantation of adipose-derived mesenchymal stem cells attenuates cerebral ischemia and reperfusion injury through suppressing apoptosis and inducible nitric oxide synthase. AB - The purpose of this study was to investigate whether autologous transplantation of adipose-derived mesenchymal stem cells (ADMSCs) has a neuroprotective effect against cerebral ischemia/reperfusion (I/R) injury in rats and to explore the possible underlying mechanisms. Adult male Sprague-Dawley rats were randomly assigned into the sham, I/R injury model (I/R), and model plus autologous transplantation of ADMSCs (ADMSC) groups. Cerebral I/R injury was induced by 2 h middle cerebral artery occlusion (MCAO) followed by reperfusion for 24 h. Rats in the I/R and ADMSC groups were intravenously injected with culture medium and ADMSCs (2.0x10(6)), respectively, at the onset of reperfusion and 12 h after reperfusion. Cerebral infarct volume was detected by triphenyltetrazolium chloride (TTC) staining. The histopathological changes and neuronal apoptosis in the ischemic penumbra were evaluated with H&E staining and the TUNEL assay, respectively. The nitric oxide (NO) content, caspase-3 activity and the Bax/Bcl-2 protein ratio were also measured. Moreover, the inducible nitric oxide synthase (iNOS) expression in the ischemic regions of rats was determined by immunohistochemical staining, quantitative real-time RT-PCR and western blot analysis. We found that autologous transplantation of ADMSCs significantly reduced the cerebral infarct volume, improved the I/R injury-induced brain damages and inhibited the neuronal apoptosis. ADMSC implantation also decreased caspase-3 activity and the Bax/Bcl-2 protein ratio, and markedly downregulated the expression of iNOS and thus prevented NO release in response to cerebral I/R injury. Taken together, our results demonstrated that autologous transplantation of ADMSCs can protect the brain against cerebral I/R injury via the inhibition of neuronal apoptosis and iNOS expression. PMID- 22322420 TI - The application of an optically switched dielectrophoretic (ODEP) force for the manipulation and assembly of cell-encapsulating alginate microbeads in a microfluidic perfusion cell culture system for bottom-up tissue engineering. AB - This study reports the utilisation of an optically switched dielectrophoretic (ODEP) force for the manipulation and assembly of cell-encapsulating alginate microbeads in a microfluidic perfusion cell culture system for bottom-up tissue engineering. One of the key features of this system is the ODEP force-based mechanism, which allows a commercial projector to be coupled with a computer to manipulate and assemble cell-encapsulating microbeads in an efficient, manageable, and user-friendly manner. Another distinctive feature is the design of the microfluidic cell culture chip, which allows the patterned cell encapsulating microbeads to be cultivated on site under culture medium perfusion conditions. For demonstrating its application in bottom-up cartilage tissue engineering, chondrocyte-encapsulating alginate microbeads varying in encapsulated cell densities were generated. The manipulation forces associated with operating the alginate microbeads were experimentally evaluated. The results revealed that the measured manipulation forces increased with increases in both the applied electric voltage and the number of cells in the alginate microbeads. Nevertheless, the observed manipulation force was found to be independent of the size of the cell-free alginate microbeads. It can be speculated that the friction force may influence the estimation of the ODEP force within the experimental conditions investigated. In this study, chondrocyte-encapsulating alginate microbeads with three different cell densities were manipulated and assembled in the proposed microfluidic system to form a compact sheet-like cell culture construct that imitates the cell distribution in the cross-section of native articular cartilage. Moreover, the demonstration case also showed that the cell viability of the cultured cells in the microfluidic system remained as high as 96 +/- 2%. In this study, four sheet-like cell culture constructs were stacked to create a larger assembled cell culture construct. The cell distribution inside the cell culture construct was further confirmed by a confocal microscopy observation, which showed that the distribution was similar to that in native articular cartilage. As a whole, the proposed system holds great promise as a platform for engineering tissue constructs with easily tunable inner cell distributions. PMID- 22322421 TI - Distribution and Y397 phosphorylation of focal adhesion kinase on follicular development in the mouse ovary. AB - Several protein tyrosine kinases (PTKs) are identified as follicle survival factors that suppress apoptosis in granulosa cells. Focal adhesion kinase (FAK/PTK2) interacts with numerous signaling partners and is important for cell adhesion, survival and other vital processes in which FAK autophosphorylation at Y397 (pY397 FAK) is critical for activating signaling pathways. Despite its important roles in apoptosis, the expression and function of FAK in the ovaries remain unknown. Here, we describe FAK expression, including pY397 FAK, in normal healthy mouse ovaries and its association with follicular development and/or atresia. Normal healthy mouse ovaries were used for western blot (n > 60) and immunohistochemical (n > 180) analyses. Western blot results in immature and mature mice revealed that total FAK and pY397 FAK were highly expressed in the ovary and immunohistochemistry results in 3-week-old mice showed they were localized to granulosa cells of ovarian follicles, especially preantral follicles. In 3-week-old mice treated with 5 IU pregnant mare serum gonadotropin (for obtaining homogenous populations of growing or atretic follicles), western blotting revealed that follicular atresia progression involved decreased phosphorylation of Y397 at 72 and 96 h after treatment, particularly in granulosa cells of atretic follicles, as shown by immunohistochemistry results at 72 h after treatment. Moreover, immunostaining patterns of FAK and cleaved caspase-3 were negatively correlated in serial sections of 3-week-old mouse ovaries. These results suggest that FAK is most active in ovarian follicle granulosa cells and that its phosphorylation at Y397 is histologically meaningful in follicular development in normal healthy ovaries. PMID- 22322422 TI - Missing mitochondrial Mpv17 gene function induces tissue-specific cell-death pathway in the degenerating inner ear. AB - The Mpv17 gene encodes a mitochondrial inner-membrane protein that has been implicated in the metabolism of reactive oxygen species. The loss of function in Mpv17-/- mice leads to early sensorineural deafness associated with severe inner ear degeneration and late onset of kidney failure. The present study demonstrates that the onset of the degeneration of the cochlear neuroepithelia is related to the onset of auditory function and appears to be first restricted to the outer hair cells (OHC), which subsequently undergo rapid degeneration. At the age of 18 days, the OHC lateral membrane degenerates and extensive vacuolization of the cytoplasm is followed by lysis of the OHCs. Such degenerative processes have been seen for the first time in relation to auditory dysfunction. The structural degeneration pattern of the OHC appears to be similar to the described paraptotic processes (an alternative form of programmed cell death) discussed in the literature as a cause of cytoplasmic neurodegeneration. In contrast, the melanocyte-like intermediate cells that are of neural crest origin and that are located in the stria vascularis, undergo apoptosis, as documented ultrastructurally. A lack of Mpv17 protein function in mitochondria thus seems to initiate tissue-specific cell-death pathways resulting in the pathology seen during the degeneration process. PMID- 22322423 TI - The balance of proangiogenic and antiangiogenic VEGFA isoforms regulate follicle development. AB - Vascular endothelial growth factor A (VEGFA) has been extensively studied because of its role in follicular development and is a principal angiogenic factor essential for angiogenesis. Since vascularization of the theca layer increases as follicles progress in size through preantral and antral stages, VEGFA might influence follicle growth via the regulation of angiogenesis. However, VEGFA might also influence follicular development through nonangiogenic mechanisms, since its expression has been localized in nonvascular follicles and cells. Alternative mRNA splicing of eight exons from the VEGFA gene results in the formation of various VEGFA isoforms. Each isoform has unique properties and is identified by the number of amino acids within the mature protein. Proangiogenic isoforms (VEGFA_XXX) are encoded by exon 8a, whereas a sister set of isoforms (VEGFA_XXXB) with antiangiogenic properties is encoded by exon 8b. The antiangiogenic VEGFA_XXXB isoforms comprise the majority of VEGFA expressed in most tissues, whereas expression of the proangiogenic VEGFA isoforms is upregulated in tissues undergoing active angiogenesis. Although proangiogenic and antiangiogenic isoforms can now be distinguished from one another, many studies evaluating VEGFA in ovarian and follicular development up to now have not differentiated proangiogenic VEGFA from antiangiogenic VEGFA. Experiments from our laboratory indicate that proangiogenic VEGFA promotes follicle recruitment and early follicular development and antiangiogenic VEGFA inhibits these processes. The balance of proangiogenic versus antiangiogenic VEGFA isoforms is thus of importance during follicle development. Further studies are warranted to elucidate the way that this balance regulates follicular formation and progression. PMID- 22322424 TI - The remyelination Philosopher's Stone: stem and progenitor cell therapies for multiple sclerosis. AB - Multiple sclerosis (MS) is an autoimmune disease that leads to oligodendrocyte loss and subsequent demyelination of the adult central nervous system (CNS). The pathology is characterized by transient phases of recovery during which remyelination can occur as a result of resident oligodendroglial precursor and stem/progenitor cell activation. However, myelin repair efficiency remains low urging the development of new therapeutical approaches that promote remyelination activities. Current MS treatments target primarily the immune system in order to reduce the relapse rate and the formation of inflammatory lesions, whereas no therapies exist in order to regenerate damaged myelin sheaths. During the last few years, several transplantation studies have been conducted with adult neural stem/progenitor cells and glial precursor cells to evaluate their potential to generate mature oligodendrocytes that can remyelinate axons. In parallel, modulation of the endogenous progenitor niche by neural and mesenchymal stem cell transplantation with the aim of promoting CNS progenitor differentiation and myelination has been studied. Here, we summarize these findings and discuss the properties and consequences of the various molecular and cell-mediated remyelination approaches. Moreover, we address age-associated intrinsic cellular changes that might influence the regenerative outcome. We also evaluate the extent to which these experimental treatments might increase the regeneration capacity of the demyelinated human CNS and hence be turned into future therapies. PMID- 22322425 TI - New perspectives of tissue remodelling with neural stem and progenitor cell-based therapies. AB - Compelling evidence exists that neural stem cell-based therapies protect the central nervous system (CNS) from chronic inflammatory degeneration, such as that occurring in experimental autoimmune encephalomyelitis and stroke. It was first assumed that stem cells directly replace lost cells but it is now becoming clearer that they might be able to protect the nervous system through mechanisms other than cell replacement. In immune-mediated experimental demyelination and stroke, transplanted neural stem/precursor cells (NPCs) are able to mediate efficient bystander myelin repair and axonal rescue. This is dependent on multiple capacities that transplanted NPCs exhibit within specific microenvironments after transplantation. However, a comprehensive understanding of the mechanisms by which NPCs exert their therapeutic impact is lacking. Here we will review some of the most recent evidence--and discuss some of the likely mechanisms--that support the remarkable capacity of NPCs to cross-talk with endogenous cells and to remodel the injured nervous system when applied as novel therapeutic regimes. We foresee that the exploitation of the innate mechanisms regulating these modalities of cell-to-cell communication has realistic chances of revolutionizing most of the actual understanding of stem cell biology and its application to regenerative medicine and CNS repair. PMID- 22322427 TI - How to choose needles and probes for ultrasonographically guided percutaneous breast biopsy: a systematic approach. AB - This article describes a systematic approach to choosing needles and probes for ultrasonographically guided (US-guided) percutaneous breast biopsy under various circumstances. The accuracy of US-guided percutaneous breast biopsy depends upon both the method chosen and lesion characteristics. Target accuracy and proper procedures are essential for predicting the yield regardless of the method chosen. Considering accuracy and cost, vacuum-assisted biopsy (VAB) should be offered only to appropriately selected patients. In particular, VAB should be the first choice for US-guided percutaneous breast biopsy of non-mass-like lesions. PMID- 22322426 TI - Rainbow trout (Oncorhynchus mykiss) shift the age composition of circulating red blood cells towards a younger cohort when exposed to thermal stress. AB - Freshwater fish, such as the rainbow trout, are commonly exposed to temperature fluctuations in their aquatic environment. Exposure to increased temperatures places fish under respiratory stress and increases the likelihood of protein misfolding and degradation that could eventually lead to cell death. Previously, we showed that genes associated with the cellular stress response, apoptosis and hematopoiesis are upregulated in the red blood cells (RBCs) of rainbow trout post thermal stress, leading to the hypothesis that a tightly regulated interaction between cell repair and cell death is occurring after heat stress. To test this hypothesis, we tracked changes in age class composition and markers of apoptosis in circulating RBCs within individual trout during exposure to and recovery from acute thermal stress. RBCs did not show any indication of apoptosis or necrosis following acute heat stress; however, we observed significant increases in numbers of early, juvenile and dividing RBCs. We also observed a shift in the composition of the circulating RBCs towards a younger cohort following heat shock through release of stored cells from the spleen and an increase in the maturation rate of early RBCs. These results suggest that the genes activated by increased temperature provided sufficient protection against thermal stress in the RBC, subsequently preventing the triggering of the cell death cascade. PMID- 22322428 TI - Maternal pre-pregnancy weight and gestational weight gain and their association with birthweight with a focus on racial differences. AB - Our objectives were to examine the interaction between maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) and their association with birthweight, with a focus on racial differences. We used birth certificate data from live singleton births of South Carolina resident mothers, who self reported their race as non-Hispanic white (NHW, n = 140, 128) or non-Hispanic black (NHB, n = 82,492) and who delivered at 34-44 weeks of gestation between 2004 and 2008 to conduct a cross-sectional study. Linear regression was used to examine the relationship between our exposures (i.e., race, BMI and GWG) and our outcome birthweight. Based on 2009 Institute of Medicine guidelines, the prevalence of adequate, inadequate and excessive GWG was 27.1, 24.2 and 48.7%, respectively, in NHW women and 24.2, 34.8 and 41.0%, respectively, in NHB women. Adjusting for infant sex, gestational age, maternal age, tobacco use, education, prenatal care, and Medicaid, the difference in birthweight between excessive and adequate GWG at a maternal BMI of 30 kg/m(2) was 118 g (95% CI: 109, 127) in NHW women and 101 g (95% CI: 91, 111) in NHB women. Moreover, excessive versus adequate GWG conveyed similar protection from having a small for gestational age infant in NHW [OR = 0.64 (95% CI 0.61, 0.67)] and NHB women [OR = 0.68 (95% CI: 0.65, 0.72)]. In conclusion, we report a strong association between excessive GWG and higher infant birthweight across maternal BMI classes in NHW and NHB women. Given the high prevalence of excessive GWG even a small increase in birthweight may have considerable implications at the population level. PMID- 22322429 TI - Low birthweight in Mexico: a systematic review. AB - There is abundant literature on the birth outcomes of women of Mexican origin living in the United States, but in most cases it does not refer to data available in Mexico. We conducted a systematic review of available data regarding low birthweight (LBW) rates in Mexico. We searched official online Mexican administrative data bases and four literature databases: OVID (Global Health), EMBASE, PubMed, and Bireme. The following inclusion criteria were used: (1) study is in English, Spanish, or Portuguese; (2) study presents data regarding LBW or birthweight distribution in Mexico; (3) study defines LBW as either < or <=2,500 g; (4) study population includes newborn children; and, (5) LBW was a primary interest of the study. Because altitude influences birthweight, it was taken into account when comparing regions. Birth certificate data showed LBW rates of 8.2% in 2008 and 8.5% in 2009 among live births with known birthweights. In 2009, high altitude (>=2,000 m) federal entities (states and Mexico City) had LBW rates higher than the median (>7.9%). States at low altitudes (<50 m) had LBW rates lower than the median, with the exception of Yucatan state. The systematic literature review identified 22 hospital-based studies and three household interview surveys that met our inclusion criteria. The hospital-based LBW rates were relatively similar to the birth certificate data and slightly lower than survey data. Data on LBW rates are available in Mexico. They should be analyzed further and used for comparative studies. PMID- 22322430 TI - Food allergy among low birthweight children in a national survey. AB - The aim of this paper was to investigate the association between birthweight and prevalence of food allergies using a national sample of US children. Adult report of birthweight and child food allergies were obtained for years 2005-2009 from the National Health Interview Survey (NHIS), a cross-sectional household survey of the US population. A total of 51,748 children aged 0-17 years were included in the analyses representing over 73 million children. Multivariable logistic regression analyses examined associations between birthweight categories and food allergies stratified by age and gender; accounting for the complex design of NHIS. Children aged 6-12 years who were born very low birthweight (500-1,499 g) were more likely to have reported food allergy compared to referent (3,000-3,499 g), OR = 1.72; 95% CI: 1.02-2.91. However, there was no clear trend of an association between birthweight and food allergy with increasing or decreasing birthweight across all ages. Estimates were generally stronger in younger male children as compared to estimates in females of the same age group. Marginal associations for respiratory allergy (OR = 1.52; 95% CI: 1.02-2.29) and hay fever (OR = 1.54; 95% CI: 0.93-2.54) were observed among very low birthweight children aged 0-5 years. There was limited evidence for a clear association between birthweight and food allergy. Marginal associations observed in children weighing 500-1,499 g at birth support efforts to minimize preterm births and very low birthweight given the increase in pediatric food allergies and the large number of children born low birthweight each year in the US. PMID- 22322431 TI - [The association between adverse events and nursing care: measurement problems]. AB - The association between adverse events and nursing care: measurement problems. Staffing of RNs below target levels has been associated with increased adverse events, included mortality. Some events may be directly associated to lack of surveillance or care, others occur as a result of neglected care and cannot be associated to the shift with levels of nurses below the target. However, a close look to negative events, neglecting positive events provides an incomplete view. Such studies have been criticized because they have not shown a direct link between the level of staffing and individual patient experiences, often did not control for sill mix and did not explore in depth what nurses do and what are their priorities when there is an higher workload. Often these studies present data with mean values ignoring that nurse staffing is not the same across an entire hospital and nursing care is delivered in geographically-based units, with wide variation in staffing levels. A future challenge of research is to combine a descriptive-quantitative approach with the collection of more qualitative data and prospective designs. PMID- 22322432 TI - [Number of nurses and adverse events: the results of a study]. AB - Number of nurses and adverse events: the results of a study. Introduction. Adverse events may be related to an higher workload and a lower nurse staffing level compared to patients needs. OBJECTIVE: To assess the association between adverse events and lower nurse staffing level compared to patients workload, measured with the Nursing Activity Score (NAS). METHOD: The daily workload of patients admitted to the Intensive Care Unit of San Gerardo Hospital (Monza) from December 15, 2009 to May 9, 2010 was measured with the NAS. The scores were correlated with the number of nurses on shift over 24 hours, the bed occupancy rate and the adverse events occurred. RESULTS: Out of a population of 240 patients for a follow-up period of 145 days, 45 adverse events were observed. In the days with events the difference between ideal and actual nurses requirement amounted to -7.68% (+/-8.84). On days without events, the difference was 0.44% (+/-7.96) (p value 0.0001). In the days with events patients received less minutes of care than needed -110.66 (+/-127), and on days without events an excess of minutes of care 6.40 (+/-115) minutes /patient. The average NAS score of patients with events was 81.88 (+/-10.00); 73.54 (+/-13.83) of those without events (p=0.001). CONCLUSIONS: In the period observed adverse events occurred mainly when the difference between patients workload according to NAS and minutes of care provided by nurses on shift was higher. PMID- 22322433 TI - [Reliability of caregivers in assessing the quality of life of stroke survivors: an explorative study]. AB - Reliability of caregivers in assessing the quality of life of stroke survivors: an explorative study. Introduction. Not all stroke survivors are able to assess their quality of life (QOL), thus a caregiver could provide important information on patients' QOL. OBJECTIVE: To assess caregiver's reliability in measuring QOL in stroke survivors. METHOD: Fifty (50) patient-caregiver dyads were recruited. Patients, hospitalized in rehabilitation facilities, were administered the Stroke Impact Scale 3.0 (SIS 3.0) patient version, the Barthel Index, the Modified Rankin Scale, and the National Institute of Health Stroke Scale. Caregivers completed the SIS 3.0 proxy version. RESULTS: The mean scores of the SIS 3.0 patient version were very similar to the proxy version and ranged from 19.1 vs 16.2 for the Hand function domain to 83.81 vs 81.85 for the Communication domain. Caregivers tended to underestimate patients' QOL although scores were not significantly different. Intraclass correlations between the patient version and the proxy version of the SIS 3.0 were highly significant (p<0.001), with coefficient over 0.80. Lower coefficients were observed for the Social participation (0.58), Emotion (0.64) and Communication (0.79) domains. CONCLUSIONS: Caregivers were more reliable in assessing the physical rather than psychosocial domains. PMID- 22322434 TI - [Assessment of pain associated to common invasive procedures and nurse's opinion]. AB - Assessment of pain associated to common invasive procedures and nurse's opinion. INTRODUCTION: Invasive diagnostic and therapeutic procedures (IDTP) may be painful and cause physical and emotional discomfort. AIM: An observational study was conducted in three medical wards of S. Giovanni Battista Hospital, to a) assess pain and discomfort experienced by patients during IDTPs and nurses' opinion; b) describe frequency and outcomes of the administration of analgesics and anxiolitics. METHODS: Pain was assessed with a Numeric Rating Scale (NRS) before and after IDTPs and patients were asked to describe the main causes of pain/discomfort experienced. Nurses expressed their opinion on pain and discomfort caused by a list of IDTPs. Means and DS sere calculated for each IDTP. RESULTS: Data on 186 patients and 200 IDTPs were collected. The most performed IDTPs were EGDS (18%), blood gas analysis (14%) and colonoscopy (12.5%). The most painful were Bone Marrow Biopsy (BOM) (NRS 7.05) and colonoscopy (NRS 6.44); those more anxiety provoking the BOM (NRS 7.26) and bronchoscopy (NRS 5.09). No analgesic or insufficient dosages were administered before some IDTPs and 56% patients would have liked it. Nurses rated patients pain and fear/anxiety significantly higher than patients. CONCLUSIONS: Acute pain, fear and anxiety are poorly controlled; the lack of protocols for pain control may be responsible for the different levels of discomfort experienced. PMID- 22322435 TI - [Lifestyle, health and cardiovascular risk: the results of the study "Rischio & Prevenzione"]. AB - Lifestyle, health and cardiovascular risk: the results of the study "Rischio & Prevenzione". The substantial agreement of the recommendations aimed to promote the so called "healthy lifestyle habits" dose not coincide to a rebut body of evidences on the transferability of the guidelines into daily conditions of care. The large cohort of ~12.000 patients included in a prospective-observational and experimental study conducted by a country-wide network of 860 Italian General Practitioners, provided the opportunity of testing the yield of the broad spectrum of life habits found across ages (>55 years, sex, regions, on the prognosis for fatal and not fatal events). While documenting and quantifying over the relative short period of time of the study (~ 4 years) the highly significant advantage of each of the components (diet and physical exercise) of the habits, as well as their combination, the study could be the sum as specifically important for two more general reasons: a) it is the general practice based documentation of the public health importance of recommendations in an adult old population; b) the instruments developed and tested to qualify-quantify the risk profiles are specifically praticable in the busy setting of daily care. PMID- 22322436 TI - [The effectiveness of the elastic bandage in reducing residual limb volume in patients with lower limb amputation: literature review]. AB - The effectiveness of the elastic bandage in reducing residual limb volume in patients with lower limb amputation: literature review. INTRODUCTION: Several banding techniques are available to contain and reduce the edema of the stump after an amputation of a limb, but there is also uncertainty on the most effective way to treat this problem. AIMS: The aim of this review is to compare the effectiveness of the elastic bandage, with other types of bandage, in reducing the stump's volume in patients with lower limb amputation. MATERIALS AND METHODS: A literature review up to april 2011 was performed on Medline, Trip Database, Ovid, CINAHL and Pedro. The outcome measure was the reduction of edema and volume of the stump expressed as circumference and number of days elapsed between the operation and the prosthesis. RESULTS: Ten articles were retrieved: five randomized controlled trials, a comparative study, a multicentre retrospective study, a retrospective audit, a case control study and a systematic review of the literature. The volume reduction of the stump of patients treated with the elastic bandage require longer compared to a stump treated with removable or semi-rigid bandage even though the gain was significant only in the first two weeks. DISCUSSION: The semi rigid and semi-rigid removable dressing are more effective in the reduction of the edema of the stump compared to the elastic bandage, but only in the short to medium term. There are, however, conflicting results on their effectiveness in the long term period (>3 weeks). PMID- 22322437 TI - [Private foundations Global Health Philanthropy: the problem of conflicts of interest]. AB - Private foundations Global Health Philanthropy: the problem of conflicts of interest. Private foundations are in a position where they are granted several privileges and are very powerful and able to influence global health. A recent article published on Plos Medicine, analyzing five of the largest health foundations highlights the network of interests and conflicts. Many private health foundations have associations with private food and pharmaceutical corporations. In some instances, these corporations directly benefit from foundations grants, and foundations in turn are invested in the corporations to which they award these grants. PMID- 22322438 TI - Detection of epigenetic variations in the protoplast-derived germlings of Ulva reticulata using methylation sensitive amplification polymorphism (MSAP). AB - Regeneration of protoplasts into de novo plants was reported for a large number of seaweed species. The regeneration of protoplasts into different morphotypes as a result of epigenetic variations was discussed for the first time in this study. The loci assessed for methylation modifications in normal filamentous thalli showed a frequency of 32.43% as unmethylated DNA, 24.32% as a hemimethylated, and 20.27% as a methylation of internal cytosine at both the strands. The corresponding methylation values for disk-type thalli were 27.02%, 32.43%, and 14.86%, respectively. The hypermethylation condition was apparent in the disk type thalli with methylation ratio of 72.97% compared to that of normal filamentous thalli with 67.56%. The frequency of methylation polymorphic sites among the two morphotypes was 53%. The present study reveals the distinct expression of cytosine methylation and is thus correlated to differential morphogenesis of plants regenerated from cultured cells. The number of protoplasts regenerating into filamentous thalli declined with increasing temperature from 15 degrees C, 20 degrees C, 25 degrees C, and 30 degrees C. The disk-type variant had higher thermal stability at 30 degrees C over normal filamentous thalli. Further, this variant could maintain itself for more than a year in the laboratory indicating its suitability for in vitro germplasm maintenance and propagation. PMID- 22322439 TI - Role of bacterial and fungal biofilms in chronic rhinosinusitis. AB - Chronic rhinosinusitis (CRS) is a very common condition that remains poorly understood from a pathogenic standpoint. Recent interest has been sparked by a potential role for biofilms in this process, with a significant body of evidence implicating them in inciting sinonasal inflammation. Biofilms are clearly present on the sinus mucosa of CRS patients, and their presence there is associated with severe disease characteristics and surgical recalcitrance. We are beginning to understand the importance of the species within these biofilms, but there may be other as-yet-unidentified factors at play in influencing disease outcomes. Recent exciting research has emerged documenting the immune response to the presence of biofilms-research that will ultimately solidify the nature and extent of the contribution of biofilms in CRS pathogenesis. Future research should focus on evidence-based antibiofilm treatments with reference to efficacy and timing of treatment. PMID- 22322440 TI - Faceting, composition and crystal phase evolution in III-V antimonide nanowire heterostructures revealed by combining microscopy techniques. AB - III-V antimonide nanowires are among the most interesting semiconductors for transport physics, nanoelectronics and long-wavelength optoelectronic devices due to their optimal material properties. In order to investigate their complex crystal structure evolution, faceting and composition, we report a combined scanning electron microscopy (SEM), transmission electron microscopy (TEM), and scanning tunneling microscopy (STM) study of gold-nucleated ternary InAs/InAs(1 x)Sb(x) nanowire heterostructures grown by molecular beam epitaxy. SEM showed the general morphology and faceting, TEM revealed the internal crystal structure and ternary compositions, while STM was successfully applied to characterize the oxide-free nanowire sidewalls, in terms of nanofaceting morphology, atomic structure and surface composition. The complementary use of these techniques allows for correlation of the morphological and structural properties of the nanowires with the amount of Sb incorporated during growth. The addition of even a minute amount of Sb to InAs changes the crystal structure from perfect wurtzite to perfect zinc blende, via intermediate stacking fault and pseudo-periodic twinning regimes. Moreover, the addition of Sb during the axial growth of InAs/InAs(1-x)Sb(x) heterostructure nanowires causes a significant conformal lateral overgrowth on both segments, leading to the spontaneous formation of a core-shell structure, with an Sb-rich shell. PMID- 22322441 TI - Patients with syndrome X have normal transmural myocardial perfusion and oxygenation: a 3-T cardiovascular magnetic resonance imaging study. AB - BACKGROUND: The pathophysiology of chest pain in patients with cardiac syndrome X remains controversial. Advances in perfusion imaging with cardiovascular magnetic resonance (CMR) now enable absolute quantification of regional myocardial blood flow (MBF). Furthermore, blood oxygen level-dependent (BOLD) or oxygenation sensitive CMR provides the unprecedented capability to assess regional myocardial oxygenation. We hypothesized that the combined assessment of regional perfusion and oxygenation with CMR could clarify whether patients with syndrome X show evidence of myocardial ischemia (reduced perfusion and oxygenation) during vasodilator stress compared with normal volunteers. METHODS AND RESULTS: Eighteen patients with syndrome X (chest pain, abnormal exercise treadmill test, normal coronary angiogram without other causes of microvascular dysfunction) and 14 controls underwent CMR scanning at 3 T. Myocardial function, scar, perfusion (2-3 short-axis slices), and oxygenation were assessed. Absolute MBF was measured during adenosine stress (140 MUg/kg per minute) and at rest by model-independent deconvolution. For oxygenation, using a T2-prepared BOLD sequence, signal intensity was measured at adenosine stress and rest in the slice matched to the midventricular slice of the perfusion scan. There were no significant differences in MBF at stress (2.35 versus 2.37 mL/min per gram; P=0.91), BOLD signal change (17.3% versus 17.09%; P=0.91), and coronary flow reserve measurements (2.63 versus 2.53; P=0.60) in patients with syndrome X and controls, respectively. Oxygenation and perfusion measurements per coronary territory were also similar between the 2 groups. More patients with syndrome X (17/18 [94%]) developed chest pain during adenosine stress than controls (6/14 [43%]; P=0.004). CONCLUSIONS: Patients with syndrome X show greater sensitivity to chest pain compared with controls but no evidence of deoxygenation or hypoperfusion during vasodilatory stress. PMID- 22322442 TI - Plumbagin, a plant derived natural agent inhibits the growth of pancreatic cancer cells in in vitro and in vivo via targeting EGFR, Stat3 and NF-kappaB signaling pathways. AB - Pancreatic cancer (PC) is the most aggressive malignant disease, ranks as the fourth most leading cause of cancer-related death among men and women in the United States. We present here that plumbagin (PL), a quinoid constituent isolated from the roots of the medicinal plant Plumbago zeylanica L, inhibits the growth of PC cells both in vitro and in vivo model systems. PL treatment induces apoptosis and inhibits cell viability of PC cells (PANC1, BxPC3 and ASPC1). In addition, i.p. administration of PL (2 mg/kg body weight, 5 days a week) in severe combined immunodeficiency (SCID) mice beginning 3 days after ectopic implantation of PANC1 cells resulted in a significant (P < 0.01) inhibition of both tumor weight and volume. PL treatment inhibited (1) constitutive expression of epidermal growth factor receptor (EGFR), pStat3Tyr705 and pStat3Ser727, (2) DNA binding of Stat3 and (3) physical interaction of EGFR with Stat3, in both cultured PANC1 cells and their xenograft tumors. PL treatment also inhibited phosphorylation and DNA-binding activity of NF-kappaB in both cultured PC cells (PANC1 and ASPC1) and in PANC1 cells xenograft tumors. Downstream target genes (cyclin D1, MMP9 and Survivin) of Stat3 and NF-kappaB were similarly inhibited. These results suggest that PL may be used as a novel therapeutic agent against human PC. Published 2012 Wiley-Liss, Inc. This article is a US Government work, and, as such, is in the public domain in the United States of America. PMID- 22322443 TI - Evaluating childhood obesity: magnetic resonance-based quantification of abdominal adipose tissue and liver fat in children. AB - PURPOSE: The purpose of this study is to establish and validate a magnetic resonance (MR)-based fat quantification package that provides an accurate assessment of abdominal adipose tissue and liver fat in children. MATERIALS AND METHODS: Ex vivo trials with a torso model and water-oil mixtures are conducted. Abdominal adipose tissue (AAT) is covered by magnetic resonance imaging (MRI) using a fat-selective sequence and is analyzed by a plug-in based on the open source software ImageJ. Liver fat (LF) is measured with localized 1H Magnetic Resonance Spectroscopy (1H MRS) and the jMRUI (java-based Magnetic Resonance User Interface) software package. Evaluation of the clinical methodology involved a study of 10 children in this feasibility study (mean age and body mass index: 13.3 yr; 33.3 kg/m2). To evaluate the method's validity, reference measurements were performed. RESULTS: Ex vivo trials with the torso model showed that adipose tissue was measured appropriately with a systematic underestimation by 9.3 +/- 0.2 % (0.32 +/- 0.064 kg). Coefficients of variation for both intra- and inter observer measurements ranged between 0 - 2.7 % and repeated analyses showed significant equivalent results (p < 0.01). The lipid content obtained by 1H MRS ex vivo revealed significant equivalence with the predefined fat content in water oil mixtures (p < 0.01). In vivo, the homemade plug-in significantly overestimated the AAT, with the visceral adipose tissue being most affected (+ 15.7 +/- 8.4 %). CONCLUSION: Although an overestimation of the AAT by the presented plug-in should be taken into consideration, this children-friendly package enables the quantification of both LF and AAT within 30 min on a freeware based platform. PMID- 22322444 TI - [Professional teeth cleaning as a rare cause of severe cervical and mediastinal soft-tissue emphysema]. PMID- 22322445 TI - Angiography and cerebral perfusion scintigraphy in balloon test occlusion of carotid artery in head and neck tumors. AB - PURPOSE: Surgery of head and neck tumors and other tumors involving the carotid artery may demand complete sacrifice of the carotid as part of the necessary tumor therapy. Sacrifice of the carotid may result in permanent brain perfusion damage. This uncorrectable procedure has to be tested beforehand in order to exclude this possibility. MATERIALS AND METHODS: In order to predict this possible unstable hemodynamic brain perfusion damage, we evaluated 12 patients with head neck tumors prior to possible sacrifice of the carotid. The following tests were applied: angiography of the neck vessels, balloon test occlusion (BTO) of the carotid lasting 10 minutes combined with perfusion reserve testing using 1000 mg acetazolamide i. v. All patients received brain perfusion scintigraphy SPECT with Tc-99 m HMPAO injected during BTO. RESULTS: All patient data were evaluated for clinical neurological defects under BTO. Perfusion of the great vessels was evaluated semiquantitatively for angiography (filling delay of the ophthalmic artery) and perfusion SPECT. None of the patients suffered from neurological defects. 9 /12 patients showed mild to severe perfusion defects. 9 /12 patients showed filling delays of more than 1 second. Both tests showed a very good correlation (p = 0.005). Only 2 /12 cases were discrepant in one degree. All severe defects were congruent in both tests. CONCLUSION: None of the patients with severe defects underwent sacrifice of the carotid. Both tests resulted in increased security regarding the prediction of possible brain perfusion damage. The combination of angiography and brain scintigraphy is logistically easy and has a high value of prediction. PMID- 22322446 TI - New highly selective colorimetric and ratiometric anion receptor for detecting fluoride ions. PMID- 22322447 TI - Ergosterol-induced sesquiterpenoid synthesis in tobacco cells. AB - Plants have the ability to continuously respond to microbial signals in their environment. One of these stimuli is a steroid from fungal membranes, ergosterol, which does not occur in plants, but acts as a pathogen-associated molecular pattern molecule to trigger defence mechanisms. Here we investigated the effect of ergosterol on the secondary metabolites in tobacco (Nicotiana tabacum) cells by profiling the induced sesquiterpenoids. Suspensions of tobacco cells were treated with different concentrations (0-1,000 nM) of ergosterol and incubated for different time periods (0-24 h). Metabolites were extracted with a selective dispersive liquid-liquid micro-extraction method. Thin layer chromatography was used as a screening method for identification of sesquiterpenoids in tobacco extracts. Liquid chromatography coupled to mass spectrometry was used for quantitative and qualitative analyses. The results showed that ergosterol triggered differential changes in the metabolome of tobacco cells, leading to variation in the biosynthesis of secondary metabolites. Metabolomic analysis through principal component analysis-scores plots revealed clusters of sample replicates for ergosterol treatments of 0, 50, 150, 300 and 1,000 nM and time dependent variation at 0, 6, 12, 18 and 24 h. Five bicyclic sesquiterpenoid phytoalexins, capsidiol, lubimin, rishitin, solavetivone and phytuberin, were identified as being ergosterol-induced, contributing to the altered metabolome. PMID- 22322448 TI - Chemisorption and reactions of small molecules on small gold particles. AB - The activity of supported gold particles for a number of oxidations and hydrogenations starts to increase dramatically as the size falls below ~3 nm. This is accompanied by an increased propensity to chemisorption, especially of oxygen and hydrogen. The explanation for these phenomena has to be sought in kinetic analysis that connects catalytic activity with the strength and extent of chemisorption of the reactants, the latter depending on the electronic structure of the gold atoms constituting the active centre. Examination of the changes to the utilisation of electrons as particle size is decreased points to loss of metallic character at about 3 nm, as energy bands are replaced by levels, and a band gap appears. Detailed consideration of the Arrhenius parameters (E and ln A) for CO oxidation points clearly to a step-change in activity at the point where metallic character is lost, as opposed to there being a monotonic dependence of rate on a physical property such as the fraction of atoms at corners or edges of particles. The deplorable scarcity of kinetic information on other reactions makes extension of this analysis difficult, but non-metallic behaviour is an unavoidable property of very small gold particles, and therefore cannot be ignored when seeking to explain their exceptional activity. PMID- 22322449 TI - The incubation of 13alpha,17-dihydroxystemodane with Cephalosporium aphidicola. AB - The biotransformation of 13alpha,17-dihydroxystemodane (3) with the fungus Cephalosporium aphidicola afforded 13alpha,17,18-trihydroxystemodane (4), 3beta,13alpha,17-tri-hydroxystemodane (5), 13alpha,17-dihydroxy-stemodan-18-oic acid (6), 3beta,11beta,13alpha,17-tetra-hydroxystemodane (7), 11beta,13alpha,17,18-tetrahydroxystemodane (8) and 3beta,13alpha,17,18-tetra hydroxystemodane (9). The hydroxylation at C-18 of the substrate points to a biosynthetically-directed transformation, because aphidicolin (2) is hydroxylated at this carbon. However, the C-3(beta) and C-11(beta) hydroxylations seem to indicate a xenobiotic biotransformation. PMID- 22322450 TI - The electronic structure of Ge9[Si(SiMe3)3]3-: a superantiatom complex. AB - We report on the electronic structure of Ge(9)[Si(SiMe(3))(3)](3)(-). Systematic density functional theory analysis of the electronic shell structure of the cluster and its derivatives reveals that the Ge(9)[Si(SiMe(3))(3)](3)(-) and its neutral counterpart have electronic shells that can be explained using the superatom model. The ligand-core interaction of these complexes is distinctly different from previously identified gold, gallium, and aluminium superatom complexes, indicating an electron-donating rather than electron-withdrawing ligand. We modify the electron-counting rule for this case and introduce a simple picture for superatom and superantiatom complexes. Discussions comparing shell models, Zintl clusters, the superhalogen Al(13) and superatom complexes to Ge(9)[Si(SiMe(3))(3)](3)(-) are presented. PMID- 22322451 TI - Involvement of the mevalonate pathway in the antiproliferative effect of zoledronate on ACHN renal cell carcinoma cells. AB - Renal cell carcinoma (RCC) has been shown to be resistant to chemotherapy and radiotherapy. In order to examine the potential of zoledronate (ZOL), a bisphosphonate, as an anticancer agent, we investigated the effects of ZOL on RCC cells and the involvement of the mevalonate pathway in antiproliferative effects, as well as the effects of ZOL administration on mice inoculated with RCC. ACHN cells were used and cell viability was measured via intra-cellular reductase activity. Chromatin condensation was detected by Hoechst 33342 staining. Proteins were detected by western blot analysis. Tumor volume was measured bidimensionally in mice inoculated with ACHN cells after vehicle or ZOL subcutaneous administration. ZOL exhibited antiproliferative effects with an IC50 value of 2.29+/-0.53 uM in ACHN cells and chromatin condensation was observed when treated with ZOL. Farnesol (FOH) and geranylgeraniol (GGOH), precursors of farnesyl pyrophosphate and geranylgeranyl pyrophosphate, exhibited potency to rescue cells treated with ZOL. Additionally, Ras and RhoA proteins located in the membrane fraction decreased when treated with ZOL and recovered by FOH or GGOH treatment, suggesting that ZOL inhibited the mevalonate pathway, thereby suppressing the translocation of prenylated Ras and RhoA proteins to membrane fractions. An in vivo study showed the inhibitory potential of ZOL on tumor growth in mice without changes in body weight. Our study showed that ZOL could be useful as an anticancer agent for the treatment of RCC, and the mevalonate pathway could be an efficient target for novel therapeutic agents against RCC. PMID- 22322452 TI - Focal adhesion kinase localizes to sites of cell-to-cell contact in vivo and increases apically in rat uterine luminal epithelium and the blastocyst at the time of implantation. AB - Focal adhesions play an important role in promoting embryo invasion; in particular, focal adhesions disassemble at the time of implantation in the rat, facilitating the detachment of the uterine luminal epithelium to allow the embryo to invade the endometrium. This study investigated focal adhesion protein, focal adhesion kinase (FAK) in the rat uterine luminal, and glandular epithelial cells to understand the dynamics of focal adhesions during early pregnancy. FAK undergoes extensive distributional change during early pregnancy, and surprisingly, FAK was not localized at the site of focal adhesions, instead being localized to the site of cell-to-cell contact and colocalizing with ZO-1 on day 1 of pregnancy. At the time of implantation, FAK increases in the apical region of the uterine luminal epithelial cells which was regulated by progesterone. Using an in vitro co-culture model of rat blastocysts attached to Ishikawa cells, FAK was present apically both in the rat blastocyst and the Ishikawa cells, suggesting a role in attachment andin mediating signal transduction between these two genetically different cell types. PMID- 22322453 TI - Current world literature. PMID- 22322455 TI - Interactions of herbivore exclusion with warming and N addition in a grass dominated temperate old field. AB - Field experiments used to explore the effects of global change drivers, such as warming and nitrogen deposition on plant productivity and species composition, have typically focused on bottom-up processes. However, both direct and indirect responses of herbivores to the treatments could result in important interactions between top-down and bottom-up effects. These interactions may be complicated by the simultaneous effects of multiple herbivore taxa. We used rodent and mollusc exclosures in the plots of a warming and N addition field experiment to examine how herbivore removal would influence plant biomass responses to the treatments. The effect of rodent exclusion on grass biomass more than doubled in response to nitrogen addition, but did not respond to warming, whereas the effect of mollusc exclusion on grass biomass increased in response to warming, but not nitrogen. In contrast, the effect of rodent exclusion on total biomass (grasses and forbs combined) increased in response to both nitrogen and warming, while the effect of mollusc exclusion on total biomass was insensitive to nitrogen and warming. In no cases were there interactions between nitrogen and warming with respect to their influence on exclosure effects. Overall, our results demonstrated substantial and variable effects of multiple herbivore taxa on plant biomass responses to warming and N addition, despite the absence of conspicuous damage to the plant canopy. These results therefore highlight the potential importance of interactions between top-down and bottom-up factors in global change field experiments. PMID- 22322456 TI - Ventriculoperitoneal shunt infection after an insect sting. PMID- 22322457 TI - Prenatal exposure to tobacco and future nicotine dependence: population-based cohort study. AB - BACKGROUND: Maternal smoking during pregnancy may increase the risk of nicotine dependence, especially in girls, but data are conflicting and confounding by other familial factors cannot be ruled out. AIMS: To clarify the relationship between prenatal tobacco exposure and adolescent tobacco uptake and dependence in boys and girls respectively, while taking confounding factors into close consideration. METHOD: We conducted a prospective longitudinal study, comprising 3020 Swedish youths followed from 11 to 18 years of age. Exposure and outcome information was elicited via self-administered parental and repeated youth questionnaires. Hazard ratios (HRs), odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated as measures of associations. RESULTS: Girls prenatally exposed to maternal tobacco use had a two- to threefold increased odds of experiencing a high number of withdrawal symptoms (OR = 2.83, 95% CI 1.68-4.87), craving for tobacco (OR = 2.04, 95% CI 1.28-3.32) and heavy tobacco use (five or more cigarettes or snus dips per day) (OR = 1.93, 95% CI 1.30-2.86). These associations were weaker among boys, and did not reach formal statistical significance. Associations between prenatal tobacco exposure and onset of regular tobacco use in both genders appeared to be mostly explained by parents' social position and postnatal smoking behaviour. CONCLUSIONS: Prenatal exposure to tobacco is linked to an increased risk of nicotine dependence among adolescent girls. PMID- 22322458 TI - Brief eclectic psychotherapy v. eye movement desensitisation and reprocessing therapy for post-traumatic stress disorder: randomised controlled trial. AB - BACKGROUND: Trauma-focused cognitive-behavioural therapy (CBT) and eye movement desensitisation and reprocessing therapy (EMDR) are efficacious treatments for post-traumatic stress disorder (PTSD), but few studies have directly compared them using well-powered designs and few have investigated response patterns. AIMS: To compare the efficacy and response pattern of a trauma-focused CBT modality, brief eclectic psychotherapy for PTSD, with EMDR (trial registration: ISRCTN64872147). METHOD: Out-patients with PTSD were randomly assigned to brief eclectic psychotherapy (n = 70) or EMDR (n = 70) and assessed at all sessions on self-reported PTSD (Impact of Event Scale - Revised). Other outcomes were clinician-rated PTSD, anxiety and depression. RESULTS: Both treatments were equally effective in reducing PTSD symptom severity, but the response pattern indicated that EMDR led to a significantly sharper decline in PTSD symptoms than brief eclectic psychotherapy, with similar drop-out rates (EMDR: n = 20 (29%), brief eclectic psychotherapy: n = 25 (36%)). Other outcome measures confirmed this pattern of results. CONCLUSIONS: Although both treatments are effective, EMDR results in a faster recovery compared with the more gradual improvement with brief eclectic psychotherapy. PMID- 22322459 TI - Alcohol use disorders and the course of depressive and anxiety disorders. AB - BACKGROUND: Inconsistent findings have been reported on the role of comorbid alcohol use disorders as risk factors for a persistent course of depressive and anxiety disorders. AIMS: To determine whether the course of depressive and/or anxiety disorders is conditional on the type (abuse or dependence) or severity of comorbid alcohol use disorders. METHOD: In a large sample of participants with current depression and/or anxiety (n = 1369) we examined whether the presence and severity of DSM-IV alcohol abuse or alcohol dependence predicted the 2-year course of depressive and/or anxiety disorders. RESULTS: The persistence of depressive and/or anxiety disorders at the 2-year follow-up was significantly higher in those with remitted or current alcohol dependence (persistence 62% and 67% respectively), but not in those with remitted or current alcohol abuse (persistence 51% and 46% respectively), compared with no lifetime alcohol use disorder (persistence 53%). Severe (meeting six or seven diagnostic criteria) but not moderate (meeting three to five criteria) current dependence was a significant predictor as 95% of those in the former group still had a depressive and/or anxiety disorder at follow-up. This association remained significant after adjustment for severity of depression and anxiety, psychosocial factors and treatment factors. CONCLUSIONS: Alcohol dependence, especially severe current dependence, is a risk factor for an unfavourable course of depressive and/or anxiety disorders, whereas alcohol abuse is not. PMID- 22322460 TI - Trends in national suicide rates for Scotland and for England & Wales, 1960-2008. AB - BACKGROUND: Suicide rates in Scotland have increased markedly relative to those in England in recent decades. AIMS: To compare changing patterns of suicide risk in Scotland with those in England & Wales, 1960-2008. METHOD: For Scotland and for England & Wales separately, we obtained national data on suicide counts and population estimates. Gender-specific, directly age-standardised rates were calculated. RESULTS: We identified three distinct temporal phases: 1960-1967, when suicide rates in England & Wales were initially higher than in Scotland, but then converged; 1968-1991, when male suicide rates in Scotland rose slightly faster than in England & Wales; and 1992-2008, when there was a marked divergence in national trends. Much of the recent divergence in rates is attributable to the rise in suicide among young men and deaths by hanging in Scotland. Introduction of the 'undetermined intent' category in 1968 had a significant impact on suicide statistics across Great Britain, but especially so in Scotland. CONCLUSIONS: Differences in temporal patterns in suicide risk between the countries are complex. Reversal of the divergent trends may require a change in the perception of hanging as a 'painless' method of suicide. PMID- 22322461 TI - Tumor-released survivin induces a type-2 t cell response and decreases cytotoxic T cell function, in vitro. AB - Clinical studies of T cell profiles from cancer patients have shown a skewing toward a type-2 T cell response with decreased cytotoxic T cell function. However, the primary cause of this shift remains unknown. Here we show that tumor released Survivin, an inhibitor of apoptosis (IAP) protein and tumor-specific antigen, is taken up by T cells and alters their response. The addition of Survivin to T cell cultures resulted in decreased T cell proliferation and reduced cytotoxic CD8(+) T cell function. Additionally, type 1 cell numbers and IFN-gamma and IL-2 production were significantly reduced, while IL-4 release and type 2 T cell numbers increased. In contrast, the function and numbers of Th17 and T regulatory cells were not affected. These studies show that tumor-released Survivin modulates T cells resulting in a phenotype similar to that observed in cancer patients with a polarity shift from a type 1 to a type 2 response. PMID- 22322462 TI - MicroRNA-21-mediated regulation of Sprouty2 protein expression enhances the cytotoxic effect of 5-fluorouracil and metformin in colon cancer cells. AB - Sprouty2 (Spry2) was identified recently as a tumor suppressor gene in cancer cells which inhibits the activation of receptor tyrosine kinases (RTKs). The present study explored the effect of Spry2 in colon cancer cells in order to assess its potential use in the treatment of colon cancer. Expression of Spry2 inhibited the growth of a colon cancer cell line, HCT116, and induced sensitization to fluorouracil (5-FU) and metformin. Spry2 promoted apoptosis of cancer cells in association with activation of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) pathway and the blockade of Ras-Raf-Erk signaling. Treatment of Spry2-HCT116 cells with metformin resulted in a more prominent effect on the inhibition of cell migration. Inhibition of microRNA-21 (mir-21) induced upregulation of Spry2 and PTEN which underscores the importance of mir-21 in Spry2-associated tumorigenesis of the colon. These results point toward a potential strategy for colon cancer treatment worthy of further investigation. PMID- 22322463 TI - Proteomic analysis of ovarian cancer cell responses to cytotoxic gold compounds. AB - Platinum-based chemotherapy is the primary treatment for human ovarian cancer. Overcoming platinum resistance has become a critical issue in the current chemotherapeutic strategies of ovarian cancer as drug resistance is the main reason for treatment failure. Cytotoxic gold compounds hold great promise to reach this goal; however, their modes of action are still largely unknown. To shed light on the underlying molecular mechanisms, we performed 2-DE and MS analysis to identify differential protein expression in a cisplatin-resistant human ovarian cancer cell line (A2780/R) following treatment with two representative gold compounds, namely Auranofin and Auoxo6. It is shown that Auranofin mainly acts by altering the expression of Proteasome proteins while Auoxo6 mostly modifies proteins related to mRNA splicing, trafficking and stability. We also found that Thioredoxin-like protein 1 expression is greatly reduced after treatment with both gold compounds. These results are highly indicative of the likely sites of action of the two tested gold drugs and of the affected cellular functions. The implications of the obtained results are thoroughly discussed in the frame of current knowledge on cytotoxic gold agents. PMID- 22322464 TI - Radial elasticity of multi-walled boron nitride nanotubes. AB - We investigated the radial mechanical properties of multi-walled boron nitride nanotubes (MW-BNNTs) using atomic force microscopy. The employed MW-BNNTs were synthesized using pressurized vapor/condenser (PVC) methods and were dispersed in aqueous solution using ultrasonication methods with the aid of ionic surfactants. Our nanomechanical measurements reveal the elastic deformational behaviors of individual BNNTs with two to four tube walls in their transverse directions. Their effective radial elastic moduli were obtained through interpreting their measured radial deformation profiles using Hertzian contact mechanics models. Our results capture the dependences of the effective radial moduli of MW-BNNTs on both the tube outer diameter and the number of tube layers. The effective radial moduli of double-walled BNNTs are found to be several-fold higher than those of single-walled BNNTs within the same diameter range. Our work contributes directly to a complete understanding of the fundamental structural and mechanical properties of BNNTs and the pursuits of their novel structural and electronics applications. PMID- 22322465 TI - Bedside ultrasound in the diagnosis of orbital cellulitis and orbital abscess. PMID- 22322466 TI - [The GRAVITAS study]. PMID- 22322467 TI - [Cardiology online: impact and pitfalls of Internet medical news]. AB - Twenty years ago, the main sources for physicians seeking information on new procedures, drugs, or devices were meetings and medical journals. The dawn of the Internet radically transformed how news and information is delivered and absorbed, beginning with the launch of online journals back in the mid-1990s. A decade and a half later, physicians can learn about new innovations the moment they are made public, and they can get that news from their phones and tablets, their Twitter or Facebook accounts, or via their favorite blog or medical news web site. Along with the clear advantages of accessing new medical information any time of day comes the need for physicians to be aware of the pitfalls of online medical content and to have a heightened sense of responsibility when it comes to integrating information gleaned online into their medical practices. PMID- 22322468 TI - [Almanac 2011: Valvular heart disease. Review of select studies that have driven recent advances in clinical cardiology: in the care of the Editors' Network Task Force of the European Society of Cardiology]. PMID- 22322469 TI - [Bicuspid aortic valve]. AB - Bicuspid aortic valve (BAV) is the most common congenital heart disease, whose natural history is characterized by the incidence of clinically relevant valvular (stenosis, regurgitation, endocarditis) and/or vascular complications regarding the thoracic aorta (dilation, aneurysm, dissection) and, rarely, intracranial and epiaortic arteries. BAV may be heritable, with an autosomal dominant pattern of inheritance with reduced penetrance; moreover, some data suggest that BAV and thoracic aorta aneurysm are independent manifestations of a single gene defect. The prevalence of BAV and its susceptibility to valvular and aortic complications during the whole life result into the need of strict clinical follow-up and appropriate therapies (medical as well as surgical) to be addressed according to guidelines specifically designed for these patients. PMID- 22322470 TI - [Perivalvular leak assessment and closure: role of real-time three-dimensional transesophageal echocardiography]. AB - Perivalvular leak following implant of aortic or mitral prosthetic valves or rings is a relatively common complication, sometimes leading to significant clinical and hemodynamic consequences, such as severe valvular insufficiency, heart failure and hemolysis. In these cases, a second surgical operation, which typically involves the replacement of the dehiscent prosthesis, is the procedure of choice, but sometimes it cannot be performed. The alternative to reoperation can be the percutaneous closure of the perivalvular leak guided by transesophageal echocardiography before and during the closure procedure. In this review, the current role of echocardiography in the study of perivalvular leaks, with particular reference to guiding percutaneous transcatheter closure, is discussed. Also, the advantages and limitations of conventional two-dimensional and real-time three-dimensional transesophageal echocardiography are compared. PMID- 22322471 TI - [Quality and appropriateness of coronary angioplasty in Lombardy: analysis of data from the registry of the Italian Society of Invasive Cardiology (SICI GISE)]. PMID- 22322472 TI - [The cost of innovation in treating aortic stenosis: transcatheter aortic valve implantation]. AB - BACKGROUND: Transcatheter aortic valve implantation (TAVI) represents a promising therapeutic option for patients affected by severe aortic stenosis, but it is currently associated with high costs. Therefore, the assessment of its economic impact becomes urgent to support decision-makers' choices about its use, patient access to treatment and reimbursement mechanisms. METHODS: A retrospective, observational, single-center (the teaching hospital located in Bologna, Italy) study was conducted. All patients with severe symptomatic aortic stenosis undergoing TAVI during the enrolment period (February 2008-August 2010) were included. The procedures were performed with both bioprostheses approved for clinical use and through different vascular access: CoreValve transfemoral (CV TF), CoreValve transsubclavian (CV-TS), Edwards Sapien transapical (ES-TA), Edwards Sapien transfemoral (ES-TF). Costs of the whole index hospitalization have been calculated from the hospital perspective. Healthcare resource consumption was measured at patient level and assessed using unit costs (micro costing approach). RESULTS: Overall, 87 consecutive patients (48 CV-TF, 12 CV-TS, 20 ES-TA, 7 ES-TF) were included in the study. They presented a high-risk profile (age 83.3 +/- 5.4 years; logistic EuroSCORE 23.3 +/- 12.3%) and important comorbidity. In-hospital mortality was 3.4%. Total cost of hospitalization was, on average, ?35.841 (range ?27.267-69.744) of which 68% was attributable to the procedure. A huge variation in costs was observed among different treatment groups. Patients treated with transfemoral implant (CV-TF: ?33.977; ES-TF: ?31.442) were on average less expensive than others (CV-TS: ?37.035; ES-TA: ?41.139). CONCLUSIONS: Our findings show that treating patients with TAVI places a heavy burden on hospital budget. Hence, due to the shortage of financial resources, affordability of TAVI requires further attention. PMID- 22322473 TI - [Epidemiology of Tako-tsubo cardiomyopathy: the Tuscany Registry for Tako-tsubo Cardiomyopathy ]. AB - BACKGROUND: Tako-tsubo (stress) cardiomyopathy (TTC) is a recently described acute cardiac syndrome that mimics ST-segment elevation myocardial infarction. The TTC Tuscany Registry is an observational prospective multicenter registry established to define the prevalence, epidemiology and prognosis of TTC in the Tuscany area. METHODS: From January 1 to December 31, 2009, 105 consecutive patients hospitalized in the 14 Cardiology Units of the Tuscany Region with a diagnosis of TTC, were enrolled in the registry. TTC diagnosis was made using the Mayo Clinic modified criteria. Clinical, instrumental, laboratory and 6-month follow-up data were collected. Results. TTC represented 1.2% of all myocardial infarctions in the Tuscany Region during 2009, and it was diagnosed in 0.6% of the angiographic exams performed during the same year. The data collected showed that TTC affects mainly the female gender (91%) in the post-menopausal period (70 +/- 11 years), though 5% of patients were <=50 years old. An antecedent stressful event was frequently detected (74%). The main clinical presentation was chest pain (86%), associated with ST-segment elevation (59%). Mean left ventricular ejection fraction on admission was 40 +/- 9%, and was associated with apical (37%), midapical (49%) or midventricular (5%) wall motion abnormalities. Left ventricular ejection fraction recovered to 51 +/- 9% in 7 +/- 9 days. Heart failure was the most common complication in the acute phase (14%), and 4 patients presented with cardiogenic shock. No patient died during the index hospitalization. At 6-month follow-up, no patient had TTC recurrence, 9 patients were rehospitalized (7 for noncardiac disease) and 2 patients died of noncardiac causes. CONCLUSIONS: Our data, which represent the largest prospective series of patients with a diagnosis of TTC, show that the prevalence of TTC in Tuscany is similar that described in other national and international studies. Moreover, the data highlight that TTC may occur also in male patients and in patients aged <50 years. The mid-term prognosis is good, but the risk of acute complications related to heart failure cannot be neglected. PMID- 22322474 TI - [Transcatheter aortic valve implantation in bicuspid aortic valve: never say never]. AB - Transcatheter aortic valve implantation (TAVI) is an emerging alternative technique that has shown promise in the treatment of severe aortic stenosis in patient populations at high risk with conventional surgery. The presence of a bicuspid aortic valve (BAV) has been considered an exclusion criterion for TAVI, because of the presumed risk for poor seating or paravalvular regurgitation due to severe distortion of the native valve leaflets. For this reason, BAV disease has generally been an exclusion criterion in major trials of TAVI and there is little clinical experience available. We report a case of transcatheter valve replacement in a poor surgical candidate with BAV stenosis using a new 29 mm Edwards Sapien prosthesis. PMID- 22322475 TI - [Letter to the editor. Vector cardiography]. PMID- 22322478 TI - The EFSUMB Guidelines on the Non-hepatic Clinical Applications of Contrast Enhanced Ultrasound (CEUS): a new dawn for the escalating use of this ubiquitous technique. PMID- 22322479 TI - Ultrasound in portal hypertension--part 2--and EFSUMB recommendations for the performance and reporting of ultrasound examinations in portal hypertension. PMID- 22322477 TI - Diabetes-specific nutrition algorithm: a transcultural program to optimize diabetes and prediabetes care. AB - Type 2 diabetes (T2D) and prediabetes have a major global impact through high disease prevalence, significant downstream pathophysiologic effects, and enormous financial liabilities. To mitigate this disease burden, interventions of proven effectiveness must be used. Evidence shows that nutrition therapy improves glycemic control and reduces the risks of diabetes and its complications. Accordingly, diabetes-specific nutrition therapy should be incorporated into comprehensive patient management programs. Evidence-based recommendations for healthy lifestyles that include healthy eating can be found in clinical practice guidelines (CPGs) from professional medical organizations. To enable broad implementation of these guidelines, recommendations must be reconstructed to account for cultural differences in lifestyle, food availability, and genetic factors. To begin, published CPGs and relevant medical literature were reviewed and evidence ratings applied according to established protocols for guidelines. From this information, an algorithm for the nutritional management of people with T2D and prediabetes was created. Subsequently, algorithm nodes were populated with transcultural attributes to guide decisions. The resultant transcultural diabetes-specific nutrition algorithm (tDNA) was simplified and optimized for global implementation and validation according to current standards for CPG development and cultural adaptation. Thus, the tDNA is a tool to facilitate the delivery of nutrition therapy to patients with T2D and prediabetes in a variety of cultures and geographic locations. It is anticipated that this novel approach can reduce the burden of diabetes, improve quality of life, and save lives. The specific Southeast Asian and Asian Indian tDNA versions can be found in companion articles in this issue of Current Diabetes Reports. PMID- 22322480 TI - Lipid peroxidation and DNA adduct formation in lymphocytes of premenopausal women: Role of estrogen metabolites and fatty acid intake. AB - A diet high in linoleic acid (an omega-6 PUFA) increased the formation of miscoding etheno (epsilon)--DNA adducts in WBC-DNA of women, but not in men (Nair et al., Cancer Epidemiol Biomark Prev 1997;6:597-601). This gender specificity could result from an interaction between omega-6 PUFA intake and estrogen catabolism, via redox-cycling of 4-hydroxyestradiol (4-OH-E(2) ) and subsequent lipid peroxidation (LPO). In this study, we investigated whether in premenopausal women LPO-derived adducts in WBC-DNA are affected by serum concentration of 2- and 4-hydroxyestradiol metabolites and by fatty acid intake. DNA extracted from buffy coat and plasma samples, both blindly coded from healthy women (N = 124, median age 40 year) participating in the EPIC-Heidelberg cohort study were analyzed. Three LPO-derived exocyclic DNA adducts, epsilondA, epsilondC and M(1) dG were quantified by immuno-enriched (32) P-postlabelling and estradiol metabolites by ultra-sensitive GC-mass spectrometry. Mean M(1) dG levels in WBC DNA were distinctly higher than those of epsilondA and epsilondC, and all were positively and significantly interrelated. Serum levels of 4-OH-E(2) , but not of 2-OH-E(2) , metabolites were positively related to etheno DNA adduct formation. Positive correlations existed between M(1) dG levels and linoleic acid intake or the ratios of dietary linoleic acid/oleic acid and PUFA/MUFA. Aerobic incubation of 4-OH-E(2) , arachidonic acid and calf thymus DNA yielded two to threefold higher etheno DNA adduct levels when compared with assays containing 2-OH-E(2) instead. In conclusion, this study is the first to compare M(1) dG and etheno-DNA adducts and serum estradiol metabolites in human samples in the same subjects. Our results support a novel mechanistic link between estradiol catabolism, dietary omega-6 fatty acid intake and LPO-induced DNA damage supported by an in vitro model. Similar studies in human breast epithelial tissue and on amplification of DNA-damage in breast cancer patients are in progress. PMID- 22322481 TI - Green tea consumption: an alternative approach to managing oral lichen planus. AB - Oral lichen planus (OLP) is a T-cell-mediated inflammatory autoimmune disease, whose pathogenesis includes both antigen-specific and non-specific mechanisms. Antigen-specific mechanisms in OLP consist of antigen presentation, lymphocyte activation, proliferation and migration as well as keratinocyte apoptosis mediated by CD8(+) cytotoxic T-cells, whereas non-specific mechanisms include mast cell degranulation and matrix metalloproteinase (MMP) activation in OLP lesions. Deficient antigen-specific transforming growth factor-beta (TGF-beta) mediated immunosuppression may also contribute to the pathogenesis of OLP. In addition, OLP is considered to be a potentially malignant disorder with a malignant transformation rate of 0-5.3%. Green tea, especially epigallocatechin-3 gallate, possesses anti-inflammatory and chemopreventive properties. It can inhibit antigen presentation, T-cell activation, proliferation and migration, keratinocyte apoptosis, nuclear factor-kappaB (NF-kB) activation and MMP-9 activity, as well as regulated on activation, normal T-cell expressed and secreted (RANTES) expression, and can modulate the imbalance between TGF-beta and interferon-gamma signaling, all of which are involved in the pathogenesis of OLP. Thus, our hypothesis is that green tea consumption may decrease OLP incidence and provide a neoteric, nontoxic and inexpensive therapeutic strategy for OLP. Furthermore, green tea might be a possible agent for preventing malignancies in OLP. PMID- 22322483 TI - Oxo iron(IV) as an oxidative active intermediate of p-chlorophenol in the Fenton reaction: a DFT study. AB - Debate continues over which active species plays the role of oxidative agent during the Fenton reaction-the HO radical or oxo iron [Fe(IV)O](2+). In this context, the present study investigates the oxidation of p-chlorophenol by [Fe(IV)O(H(2)O)(5)](2+) using DFT calculations, within gas-phase and micro solvated models, in order to explore the possible role of oxo iron as a reactant. The results show that the chlorine atom substitution of p-chlorophenol by oxo iron is a highly stabilising step (DeltaH = -83 kcal mol(-1)) with a free energy barrier of 5.8 kcal mol(-1) in the micro-solvated model. This illustrates the high oxidising power of the [Fe(IV)O(H(2)O)(5)](2+) complex. On the other hand, the breaking of the Fe-O bond, leading to the formation of hydroquinone, is observed to be the rate-determining step of the reaction. The rather large free energy barrier corresponding to this bond cleavage amounts to 10.2 and 9.3 kcal mol(-1) in the gas-phase and micro-solvated models, respectively. Elsewhere, the lifetime of the HO radical has previously been shown to be extremely small. These facts, combined with observations of oxo iron under certain experimental conditions, suggest that oxo iron is a highly plausible oxidative species of the reaction. In addition, a trigonal bipyramidal iron complex, coordinated either by hydroxyl groups and/or by water molecules, has been found in all described mechanisms. This structure appears to be a stable intermediate; and to our knowledge, it has not been characterised by previous studies. PMID- 22322482 TI - Effects of 1,25-(OH)(2)D (3) on the expressions of vitamin D receptor, STAT5 and cytoskeletal rearrangement in human monocytes incubated with sera from type 2 diabetes patients and diabetic nephropathy patients with uremia. AB - OBJECTIVE: To explore the effects of 1,25-(OH)(2)D(3) and lipopolysaccharide (LPS) plus human recombinant interleukin-15 (IL-15) on expression of vitamin D receptor (VDR) and STAT5, and cytoskeletal rearrangement in human monocytes incubated with sera from type 2 diabetes (T2DM) patients and diabetic nephropathy (DN) patients with uremia. MATERIALS AND METHODS: Peripheral sera were isolated from healthy volunteers (control group, T2DM patients and DN uremic non-dialysis patients). After incubation with or without 1,25(OH)(2)D(3), THP-1 monocytes were treated with LPS plus IL-15 prior to the collection of cells and supernatants. VDR mRNA transcription was examined by RT-PCR, whilst THP-1 monocytic VDR, STAT5 and p-STAT5 expressions were investigated by Western blotting. Concentrations of IL-6 and monocyte chemoattractant protein-1 (MCP-1) in supernatants were assessed by ELISA. Immunofluorescence and a laser confocal microscopy was used to examine the expression of VDR and cytoskeletal proteins. RESULTS: Compared to the normal control, LPS and IL-15 down-regulate monocytic VDR expression in T2DM patients and DN uremic patients, whilst with cytoskeletal rearrangement, they up-regulate p-STAT5 expression as well as IL-6 and MCP-1 activity. Such effects could be in part blocked by 1,25-(OH)(2)D(3). CONCLUSION: The above results suggest that the anti-inflammatory mechanism of 1,25-(OH)(2)D(3) may be related to cytoskeletal proteins, VDR and STAT5 signaling pathway. PMID- 22322484 TI - Development of peripapillary venous loop in an eye with a small optic disc. PMID- 22322485 TI - Excimer laser smoothing of endothelial keratoplasty grafts. AB - PURPOSE: To use excimer laser smoothing passes to reshape Descemet-stripping automated endothelial keratoplasty (DSAEK) endothelial grafts and to evaluate the effect on the donor endothelium. METHODS: The stromal surface of microkeratome cut DSAEK grafts was smoothed using excimer laser smoothing passes with masking fluid. Excimer laser hyperopic ablation was used to improve the uniformity of graft thickness within the optical zone. Fourier-domain optical coherence tomography was used to measure endothelial graft pachymetry, plan ablations, and evaluate donor contour. Vital dye staining was performed to assess endothelial cell damage. Scanning electron microscopy images of stromal surfaces were graded on a 5-point scale by masked observers to evaluate surface roughness. RESULTS: Four grafts underwent excimer laser smoothing. Vital dye staining showed no endothelial damage. Microkeratome-cut surfaces treated with laser smoothing (mean grade = 2.04) were smoother than nonsmoothed microkeratome-cut surfaces (mean grade = 4.07; P < 0.01), surfaces that underwent dry laser ablation (mean grade = 3.63; P < 0.01) and manually dissected interfaces (mean grade = 4.75; P < 0.0001). No difference was observed between stromal beds created by peeling Descemet membrane (mean grade = 1.64) compared with surfaces produced by microkeratome cutting followed by laser smoothing (mean grade = 2.04; P = 0.14). One graft underwent combined excimer smoothing and peripheral hyperopic ablation. The center-periphery thickness difference was 15 MUm before ablation and 4 MUm afterward. CONCLUSIONS: Laser smoothing passes can be used to improve the contour and smoothness of DSAEK grafts without damaging donor endothelial cells. Clinical trials are needed to determine whether reshaping donors using excimer laser can deliver improved visual outcomes after DSAEK. PMID- 22322486 TI - Cranial base and maxillary changes in patients treated with Frankel' s functional regulator (1b). AB - OBJECTIVES: The purpose of this study was to assess cranial base and maxillary growth in patients with Class II-type I malocclusions when treated with Frankel' s functional regulator (FR-1b). STUDY DESIGN: The treatment group was made up of 43 patients that were divided into two groups: prepubescent (n: 28), and pubescent (n: 15). The control group included 40 patients who did not receive any kind of treatment and were likewise divided into a prepubescent group (n: 19), and a pubescent group (n: 21). A computerized cephalometric study was carried out and superimpositions were done in order to assess the antero-posterior, vertical and rotational movement of the maxilla. RESULTS: The results indicate that anterior cranial length is not affected by the regulator but the cranial deflection of the treatment group was diminished. Although a slight counterclockwise rotation effect on the upper jaw was observed due to treatment, no growth restriction of the maxilla in a vertical or antero-posterior direction was observed compared to other non-treated Class II-type I malocclusion patients. CONCLUSION: The functional regulator does not have any effect on anterior cranial length, but it does affect the angulation of the cranial base. According to our results, the appliance has demonstrated a flattening effect of the cranial base (p<0.05) in the treated sample. The functional regulator induces counterclockwise rotation rather than vertical or sagittal changes in the maxilla. PMID- 22322487 TI - Oral health and mortality risk in the institutionalised elderly. AB - OBJECTIVE: Examining oral health and oral hygiene as predictors of subsequent one year survival in the institutionalised elderly. DESIGN: It was hypothesized that oral health would be related to mortality in an institutionalised geriatric population. A 12-month prospective study of 292 elderly residing in nine geriatric institutions in Granada, Spain, was thus carried out to evaluate the association between oral health and mortality. Independent samples, T-test, chi square test and Cox regression analysis were used to analyse the data. Sixty three participants died during the 12-month follow-up. RESULTS: Mortality was increased in denture users (RR = 2.18, p= 0.007) and in people suffering severe cognitive impairment (RR = 2. 24, p= 0.003). One-year mortality was 50% in participants having both these characteristics. CONCLUSIONS: Oral hygiene was not significantly associated with mortality. Cognitive impairment and wearing dentures increased the risk of death. One-year mortality was 50% in cognitively impaired residents wearing dentures as opposed to 10% in patients without dentures and cognitive impairment. PMID- 22322488 TI - Orofacial pain of cardiac origin: review literature and clinical cases. AB - The most common types of orofacial pain originate at the dental or periodontal level or in the musculoskeletal structures. However, the patient may present pain in this region even though the source is located elsewhere in the body. One possible source of heterotopic pain is of cardiac origin. OBJECTIVES: Report two cases of orofacial pain of cardiac origin and review the clinical cases described in the literature. STUDY DESIGN: Description of clinical cases and review of clinical cases. RESULTS AND CONCLUSIONS: Nine cases of atypical pain of cardiac origin are recorded, which include 5 females and 4 males. In craniofacial structures, pain of cardiac origin is usually bilateral. At the craniofacial level, the most frequent location described is in the throat and jaw. Pain of cardiac origin is considered atypical due to its location, although roughly 10% of the cases of cardiac ischemia manifest primarily in craniofacial structures. Finally, the differential diagnosis of pain of odontogenic origin must be taken into account with pain of non-odontogenic origin (muscle, psychogenic, neuronal, cardiac, sinus and neurovascular pain) in order to avoid diagnostic errors in the dental practice as well as unnecessary treatments. PMID- 22322489 TI - Computer-aided system for morphometric mandibular index computation. (Using dental panoramic radiographs). AB - OBJECTIVE: We propose and validate a computer-aided system to measure three different mandibular indexes: cortical width, panoramic mandibular index and, mandibular alveolar bone resorption index. STUDY DESIGN: Repeatability and reproducibility of the measurements are analyzed and compared to the manual estimation of the same indexes. RESULTS: The proposed computerized system exhibits superior repeatability and reproducibility rates compared to standard manual methods. Moreover, the time required to perform the measurements using the proposed method is negligible compared to perform the measurements manually. CONCLUSIONS: We have proposed a very user friendly computerized method to measure three different morphometric mandibular indexes. From the results we can conclude that the system provides a practical manner to perform these measurements. It does not require an expert examiner and does not take more than 16 seconds per analysis. Thus, it may be suitable to diagnose osteoporosis using dental panoramic radiographs. PMID- 22322490 TI - Wetting ability of an acetone/based etch&rinse adhesive after NaOCl-treatment. AB - OBJECTIVES: to evaluate the effect of sodium hypochlorite (NaOCl) treatment on surface dentin roughness (Ra) and contact angle (CA) when using Prime&Bond NT adhesive (PB NT). STUDY DESIGN: Extracted human third molars were sectioned to expose flat, superficial and deep dentin surfaces. CA and Ra were measured (1) before and (2) after 35% H3PO4 etching, and (3) H3PO4 etching + 5% NaOCl treated for 2 minutes before the application of PB NT. CA was measured by the Axisymetric Drop Shape Analysis Technique using distilled and deionized water and PB NT. Roughness was evaluated with a profilometer, twelve radial measurements were performed in each treatment surface. Data were analyzed with two-way ANOVA and Newman-Keuls multiple comparison test procedures. RESULTS: CA values decreased after acid etching and even more after NaOCl treatment on deep dentin when water was tested. With resin, there were not differences on CA results after H3PO4 neither after NaOCl treatment, in both dentin surfaces. Etching and NaOCl treatment resulted in surface roughness increase. CONCLUSIONS: In spite of the higher roughness after NaOCl treatment on superficial and deep dentin, the use of 5% NaOCl for 2 min after dentin demineralization when PB NT was employed did not improved the wettability of dentin, probably due to nanofiller content and/or hydrogen-bonding interactions with residues of the organic matrix on collagen depleted dentin. PMID- 22322491 TI - Teaching the placement of posterior resin-based composite restorations in Spanish dental schools. AB - OBJECTIVES: In an area of esthetic dentistry such as posterior composites, in which new materials and techniques are being devolved continuously, it is important to confirm that dental students have a clear understanding of the basic principles of clinical application of this knowledge. Considering that the preparation of dental graduates in Spain may be of interest to competent dental authorities and employers with whom they can work worldwide, this study investigated the teaching of posterior composite restorations in Spanish dental schools. STUDY DESIGN: In late 2009/ early 2010, a questionnaire seeking information on the teaching of posterior composites was emailed to the professor responsible for teaching operative dentistry in each of the fifteen dental schools having complete undergraduate dental degree programmes in Spain. RESULTS: The response rate was 100%. Most investigated topics did not show noteworthy differences depending on whether the schools were public or private. Variations were found among Spanish dental schools in both the amount and content of the teaching programmes concerning posterior composite restorations. Differences were recorded in the teaching of cavity design, contraindications to composite placement, indications for liners and bases, matrix and wedging techniques, composite and bonding systems, light curing and finishing procedures for composite restorations. More consistency was observed in teaching methods of moisture-control, indirect composites and amalgam bonding. CONCLUSIONS: As recommended in previous surveyed countries, efforts must be made to promote harmonization of dental curricula to make it easier for graduates to work elsewhere, and to ensure they meet the needs of their patients on entering independent practice. PMID- 22322492 TI - Clinical profile of orofacial infections: an experience from two primary care dental practices. AB - OBJECTIVES: Orofacial infections are common reasons for dental consultations worldwide. However, there is scarcity of data on clinico-epidemiological profiles reported from primary care dental practices. To address this issue, a study was done to characterize the clinical pattern, age groups affected and sex predilection of orofacial infections in the primary care dental practice. STUDY DESIGN: Clinical data was evaluated from random electronic files of patients for whom antimicrobials were prescribed at two Dental Practices in UK between January 2009 and December 2010. RESULTS: 200 case records were studied. 104 (52%) cases were females. Mean age was 37.2 (+/-15.1) years. 107 (53.5%) cases belonged to age group 21-40 years. Posterior teeth were involved in 112 (56%) cases. Types of disease were as follows: dentoalveolar abscess 63(31.5%), pulpitis 27(13.5%), apical periodontitis 21(10.5%), pericoronitis 21(10.5%), dry socket 13(6.5%), periodontitis 9(4.5%) infected root stump 5(2.5%), facial swelling 5(2.5%) and infections unspecified 36(18%) cases. CONCLUSIONS: Orofacial infections affect both sexes equally. 21-40 years is the commonest age-group affected. Dentoalveolar abscess is the commonest infection followed by unspecified infections and pulpitis. PMID- 22322493 TI - Temporomandibular joint arthrocentesis. Review of the literature. AB - The treatment of the temporomandibular joint (TMJ) is still controversial. TMJ arthrocentesis represents a form of minimally invasive surgical treatment in patients suffering from internal derangement of the TMJ, especially closed lock. It consists of washing the joint with the possibility of depositing a drug or other therapeutic substance. Resolution of symptoms is due to the removal of chemical inflammatory mediators and changes in intra-articular pressure. Numerous clinical studies regarding this technique have been published. The goal of this paper is to review all clinical articles that have been published with regard to the critique of this technique. 19 articles with different designs fulfilling selection guidelines were chosen. A series of clinical and procedure variables were analyzed. Although the mean of improvement was higher that 80%, further research is needed to determine more homogeneous indications for TMJ athrocentesis. PMID- 22322494 TI - Oral rehabilitation with tilted dental implants: a metaanalysis. AB - OBJECTIVE: To compare the course of patients treated with tilted implants versus those treated conventionally with axial implants, analyzing the success rate and marginal bone loss. MATERIAL AND METHODS: A PubMed search was made using the key words "tilted implants ", "angled implants ", "angulated implants ", "inclined implants " and "maxillary atrophy. " A review was made of the articles published between 1999-2010. The inclusion criteria were the use of tilted implants, clinical series involving at least 10 patients, and a minimum follow-up of 12 months after prosthetic loading. The exclusion criteria were isolated clinical cases, studies with missing data, and publications in languages other than English or Spanish. The metaanalysis finally included 13 articles: 7 retrospective studies and 6 prospective studies. RESULTS: On analyzing the success rate in the retrospective studies, two reported a higher success rate with tilted implants; one a higher success rate with axial implants; and two reported similar success rates with both implants. On analyzing the success rate in the prospective studies, two reported a higher success rate with tilted implants; two a higher success rate with axial implants; and two reported similar success rates with both implants. On examining marginal bone loss, three studies reported greater bone loss with axial implants and one with tilted implants. CONCLUSIONS: There was no evidence of differences in success rate between tilted and axial implants in either the prospective or retrospective studies subjected to review. The marginal bone loss observed with the tilted and axial implants likewise proved very similar. It thus can be deduced that tilted implants exhibit the same evolutive behavior as axial implants. PMID- 22322495 TI - Antimicrobial activity and enterococcus faecalis biofilm formation on chlorhexidine varnishes. AB - OBJECTIVE: To evaluate, in vitro, the antimicrobial activity and biofilm formation of three chlorhexidine varnishes in four E. faecalis strains: E. faecalis ATCC 29212, E. faecalis EF-D1 (from failed endodontic treatment), E. faecalis 072 (cheese) and E. faecalis U-1765 (nosocomial infection), and one E. durans strain (failed endodontic treatment). STUDY DESIGN: The direct contact test was used to study the antimicrobial activity. Bacterial suspensions were exposed for one hour to EC40, Cervitec (CE) and Cervitec Plus (CEP) varnishes. "Eradication " was defined as 100% bacterial kill. The formation of enterococci biofilms was tested on the surface of the varnishes after 24 hours of incubation and expressed as percentage of biofilm reduction. RESULTS: EC40 eradicated all strains except E. faecalis ATCC 29212, where 98.78% kill was achieved. CE and CEP showed antimicrobial activity against all the strains, but most clearly against E. durans and E. faecalis 072. EC40 completely inhibited the formation of biofilm of E. faecalis ATCC 29212, E. faecalis 072 and E. durans. CE and CEP led to over 92% of biofilm reduction, except in the case of E. faecalis U-1765 on CEP (76.42%). CONCLUSION: The three varnishes studied were seen to be effective in killing the tested strains of enterococci and in inhibiting the formation of biofilm, the best results being observed with EC40. PMID- 22322496 TI - Criteria for the prescription of oral bisphosphonates for the treatment of osteoporosis in a series of women referred for tooth extraction. AB - OBJECTIVE: To evaluate the criteria for the prescription of oral bisphosphonates (OB) in a series of women with osteoporosis referred for tooth extraction. STUDY DESIGN: The study included 38 postmenopausal women on treatment with OBs. The following variables were analysed: age, weight, height, type of OB and duration of treatment, bone densitometry and risk factors for osteoporosis. In addition, the osteoporosis self-assessment tool (OST) was administered and collagen type I C-telopeptide (CTX) levels were measured. RESULTS: Bone densitometry had only been performed in six patients (15.7%) before starting OB treatment. Based on the results of the OST, nine (23.6%) of the participants presented a low risk of osteoporosis. CTX levels were measured in 23 patients: 11 (47.8%) presented values below 150 pg/ml. CONCLUSION: Although all patients in the present series were on treatment with OBs, a large percentage did not satisfy the criteria for the initiation of treatment for postmenopausal osteoporosis. PMID- 22322497 TI - Effect of aluminum chloride hemostatic agent on microleakage of class V composite resin restorations bonded with all-in-one adhesive. AB - OBJECTIVES: Since hemostatic agents can induce changes on enamel and dentin surfaces and influence composite resin adhesion, the aim of the present study was to evaluate the effect of the aluminum chloride hemostatic agent on the gingival margin microleakage of class V (Cl V) composite resin restorations bonded with all-in-one adhesive. STUDY DESIGN: Cl V cavities were prepared on the buccal surfaces of 60 sound bovine permanent incisors. Gingival margins of the cavities were placed 1.5 mm apical to the cemento-enamel junction (CEJ). The teeth were randomly divided into two groups of 30. In group 1, the cavities were restored without the application of a hemostatic agent; in group 2, the cavities were restored after the application of the hemostatic agent. In both groups all-in-one adhesive and Z250 composite resin were used to restore the cavities with the incremental technique. After finishing and polishing, the samples underwent a thermocycling procedure, followed by immersion in 2% basic fuschin solution for 24 hours. The samples were sectioned and gingival microleakage was evaluated under a stereomicroscope. The non-parametric Mann-Whitney U test was used to compare microleakage between the two groups. Statistical significance was defined at P<0.05. RESULTS: A statistically significant difference was observed in microleakage between the two groups (P<0.001). CONCLUSIONS: Contamination of Cl V composite resin restorations bonded with all-in-one adhesive with aluminum chloride hemostatic agent significantly increases restoration gingival margin microleakage. PMID- 22322498 TI - Orofacial pain of cardiac origin, serial of clinical cases. AB - OBJECTIVE: To determine the clinical characteristics of the orofacial pain of cardiac origin in patients visited when doing a treadmill exercise test, at the cardiology service of the Can Ruti Hospital in Badalona (Barcelona, Spain). STUDY DESIGN: The sample of that study included thirty patients visiteding when doing a treadmill exercise test, at the cardiology service. The questionnaire has been asked to a sample of 30 patients. RESULTS: Eleven of the 30 patients included in this study presented craniofacial pain before or during the cardiac seizure. The location of the pain was bilateral, non-irradiated at the mandible in all cases. The intensity of the pain was from slight to severe. The frequency of the appearance of the pain was paroxysmal in 8 cases and constant in three cases, and the duration was from a few hours to a maximum of 14 days. DISCUSSION: The cardiac pain in craniofacial structures is usually bilateral, compared to odontogenic pain which is always unilateral. The pain of cardiac origin is considered atypical because of its location, but about the 10 % of the cases, the cardiac ischemia has its primary manifestation in orofacial structures. CONCLUSIONS: Eleven patients referred a bilateral non-irradiated mandibular pain, with intensity from slight to severe, and with a paroxystic frequency in eight cases and a constant frequency in three cases. Just one patient referred pain during the treadmill exercise test. In all cases the pain disappeared after the cardiac surgery or the administration of vasodilators. PMID- 22322499 TI - Effects on the maxilla and cranial base caused by cervical headgear: a longitudinal study. AB - OBJECTIVES: The aim of this study is to test the possible orthopedic effects of cervical headgear on the cranial base and maxilla. STUDY DESIGN: a sample consisting of 79 subjects with skeletal class II malocclusion was divided into two groups. The experimental group was made up of 41 patients all treated with cervical headgear. The control group included a total of 38 non-treated patients. Each one of these groups was then subdivided according to age into one of three groups: prepubescent, pubescent or post-pubescent. Cephalometric parameters were compared in both groups in order to measure the cranial base angle and the vertical and sagittal position of the maxilla. Additionally, cephalometric superimpositions taken at the beginning and end of the study were compared. RESULTS: results revealed significant differences in the cranial base angle and in the SNA angle (p<0.05). However, no differences were observed in the variables that measure the maxillomandibular relationship. While no changes were noted in the palatal plane slope, a flattening of the cranial base was found caused by the cervical headgear, in addition to a retrusion of point A that does not mean there was a reduction in the maxillomandibular relationship. CONCLUSIONS: cervical headgear treatment induces cephalometric flattening of the cranial base and a decrease of the SNA angle. PMID- 22322500 TI - Simulation for training in sinus floor elevation: new surgical bench model. AB - OBJECTIVES: to describe a bench model (workshop of abilities) for sinus floor elevation (SFE) training that simulates the surgical environment and to assess its effectiveness in terms of trainees' perception. STUDY DESIGN: thirty-six randomly selected postgraduate students entered this cross-sectional pilot study and asked to fill in an anonymous, self-applied, 12-item questionnaire about a SFE workshop that included a study guide containing the workshop' s details, supervised practice on a simulated surgical environment, and assessment by means of specific check-lists. RESULTS: Thirtiy-six fresh sheep heads were prepared to allow access to the buccal vestible. Using the facial tuber, third premolar and a 3D-CT study as landmarks for trepanation, the sinus membrane was lifted, the space filled with ceramic material and closed with a resorbable membrane. The participants agreed on their ability to perform SFE in a simulated situation (median score= 4.5; range 2-5) and felt capable to teach the technique to other clinicians or to undertake the procedure for a patient under supervision of an expert surgeon (median= 4; range 1-5 ). There were no differences on their perceived ability to undertake the technique on a model or on a real patient under supervision of an expert surgeon (p=0.36). CONCLUSIONS: Clinical abilities workshops for SFE teaching are an essential educational tool but supervised clinical practice should always precede autonomous SFE on real patients. Simulation procedures (workshop of abilities) are perceived by the partakers as useful for the surgical practice. However, more studies are needed to validate the procedure and to address cognitive and communication skills, that are clearly integral parts of surgical performance. PMID- 22322501 TI - Bonding efficacy of an acetone/based etch-and-rinse adhesive after dentin deproteinization. AB - OBJECTIVES: to evaluate the effect of sodium hypochlorite (NaOCl) treatment on dentin bonding by means of shear bond strength (SBS) measurements when using Prime&Bond NT (PB NT) adhesive. Ultrastructure of the interfaces was examined by scanning electron microscopy (SEM). STUDY DESIGN: Extracted human third molars were sectioned and ground to expose flat surfaces of superficial or deep dentin. Specimens were randomly assigned to two equal groups, and bonded as follows: (1) according to the manufacturers' directions, after 35% H3PO4 etching, (2) 5% NaOCl treated for 2 minutes, after 35% H3PO4 etching. Each sample was embedded in a Watanabe shear test assembly for a single plane lap shear. After PB NT bonding, specimens were stored in water for 24 h at 37oC and thermocycled (500x). Samples were tested in shear to failure using a universal testing machine at 0.75 mm/min. Data were analyzed with ANOVA and Newman-Keuls multiple comparison test procedures. Two samples of each group were randomly selected to investigate the morphologic aspect of the resin/dentin interface with SEM. RESULTS: After etching and after aqueous sodium hypochlorite (NaOClaq) application, SBS values were similar on superficial than deep dentin (p>0.05). SEM findings shows for H3PO4 etching conditioned samples a detectable hybrid layer and long resin tags; for NaOCl treated specimens, it may be observed a non apparent hybrid layer, and the adhesive contact directly with the neck of the cylindrical resin tags. CONCLUSIONS: The use of 5% NaOCl for 2 min after dentin demineralization when PB NT was employed did not improve the bond strength to dentin, probably due to nanofiller content and/or oxidative changes on collagen-depleted dentin. PMID- 22322502 TI - Oro-facial manifestations of 100 leprosy patients. AB - OBJECTIVES: To verify the frequency of oral and facial involvement in diagnosed leprosy patients. STUDY DESIGN: This study was performed on 100 leprosy patients (62 male, 38 female, mean ages 51.86+/-6.1). After explaining the study design, we studied descriptive information including: patient' s sex, age, job, place of birth, familial history of leprosy, types of disease (lepromatous, borderline and tuberculoid leprosy), ocular and oral lesions, facial involvement and neuropathy. The statistical signification was measured by chi-square test. RESULTS: A total of 46 (23 lepromatous, 15 borderline, and 8 tuberculoid leprosy) out of 100 patients with leprosy had oral lesions. Statistical analysis did not show any significant difference in frequency of oral lesions between different types of disease. Facial lesions were presented in 57 (39 lepromatous, 10 borderline, and 8 tuberculoid leprosy) patients. There was a statistical significant difference in frequency of facial manifestations between different types of leprosy. It has to be mentioned that, atrophy of nasal spine, facial nerve involvement, ocular lesions and facial deformity were seen in 15%, 17%, 22% and 44% of leprosy patients, respectively. CONCLUSION: Examination of leprosy patients should be extended to the oral mucosa because oral mucosa may be a secondary source of M.Leprae transmission and infection. PMID- 22322503 TI - A study on the reproducibility of cephalometric landmarks when undertaking a three-dimensional (3D) cephalometric analysis. AB - OBJECTIVES: Cone Beam Computerized Tomography (CBCT) allows the possibility of modifying some of the diagnostic tools used in orthodontics, such as cephalometry. The first step must be to study the characteristics of these devices in terms of accuracy and reliability of the most commonly used landmarks. The aims were 1- To assess intra and inter-observer reliability in the location of anatomical landmarks belonging to hard tissues of the skull in images taken with a CBCT device, 2- To determine which of those landmarks are more vs. less reliable and 3- To introduce planes of reference so as to create cephalometric analyses appropriated to the 3D reality. STUDY DESIGN: Fifteen patients who had a CBCT (i-CAT) as a diagnostic register were selected. To assess the reproducibility on landmark location and the differences in the measurements of two observers at different times, 41 landmarks were defined on the three spatial axes (X,Y,Z) and located. 3.690 measurements were taken and, as each determination has 3 coordinates, 11.070 data were processed with SPSS statistical package. To discover the reproducibility of the method on landmark location, an ANOVA was undertaken using two variation factors: time (t1, t2 and t3) and observer (Ob1 and Ob2) for each axis (X, Y and Z) and landmark. The order of the CBCT scans submitted to the observers (Ob1, Ob2) at t1, t2, and t3, were different and randomly allocated. Multiple comparisons were undertaken using the Bonferroni test. The intra- and inter-examiner ICC's were calculated. RESULTS: Intra- and interexaminer reliability was high, both being ICC >= 0.99, with the best frequency on axis Z. CONCLUSIONS: The most reliable landmarks were: Nasion, Sella, Basion, left Porion, point A, anterior nasal spine, Pogonion, Gnathion, Menton, frontozygomatic sutures, first lower molars and upper and lower incisors. Those with less reliability were the supraorbitals, right zygion and posterior nasal spine. PMID- 22322504 TI - Orthodontic treatment need in a Spanish young adult population. AB - OBJECTIVES: Orthodontic treatment need has often been assessed in child populations, but few studies employing internationally-recognized indices have been conducted in adult or young adult populations. The aim of this study was to determine the orthodontic treatment need of a young adult population in Spain by means of the Dental Aesthetic Index (DAI), the Index of Orthodontic Treatment Need (IOTN) and the need perceived by the patients. STUDY DESIGN: A cross sectional epidemiological study was conducted in a broad, representative sample of 671 adults aged between 35 and 44 years using health centers in the Valencia Region of Spain, following the recommendations of the World Health Organization (WHO). RESULTS: Orthodontic treatment was required by 31.3% of the sample according to the DAI and 19.2% according to the IOTN (DHC). The orthodontic treatment need perceived by the patients was 21.1%. On relating treatment need to different variables, significant differences in patient perception were encountered by gender, as women perceived a greater need (23.9%) than men (14.4%). Significant differences in previous orthodontic treatment history were found between middle/high (15%) and low (9%) social class and between secondary/tertiary (14%) and primary (3.3%) education. CONCLUSIONS: There was no agreement between the treatment need assessed objectively by the indices and that perceived by the patient, or between the indices themselves. The decision to undergo orthodontic treatment can depend on socioeconomic and psychological factors and on values and principles that do not easily lend themselves to objective measurement. PMID- 22322505 TI - A survey of oral surgeons' tobacco-use-related knowledge and intervention behaviors. AB - OBJECTIVES: To evaluate whether oral surgeons are aware of tobacco' s role in oral health. Moreover, we wanted to know professionals' attitudes towards smoker patients and physicians' involvement in detecting and eradicating this habit in patients. STUDY DESIGN: We conducted a survey to determine the awareness of the members of the Spanish Society of Oral Surgery about tobacco' s damage on oral health and the role of dentists in the prevention and elimination of the smoking habit. RESULTS: 450 surveys were distributed during the Seventh National Congress of the Spanish Society of Oral Surgery, of which 224 (49.8%) were answered. Seventy-six point eight percent of oral surgeons said that they have a good knowledge of the effects of snuff on oral health. However, only 42.9% admitted they had received specific training regarding how to deal with patients who want to give up smoking. Sixty-three point four percent had explained to smoker patients the risk of this habit for the oral and general health. However, 17% admitted they do not advise their patients to give up smoking for fear of upsetting them, while 15.2% expressed lack of time, and 3.6% think it is not their competence. As to the relationship between oral cancer and smoking, 83% of oral surgeons recognize a direct relationship. In addition, 85.7% of professionals believe that dentists have a primary role in oral cancer prevention. CONCLUSIONS: These results indicate that most oral surgeons are concerned about the smoking habit of their patients. However, it is necessary to increase the specific training of dentists by providing tobacco treatment programs as part of their professional responsibility. Oral surgeons recognize the direct relationship between the smoking habit and oral cancer and regard as very important the role of dentists in the prevention of this disease. PMID- 22322506 TI - Thermal increase in the oral mucosa and in the jawbone during Nd:YAG laser applications. Ex vivo study. AB - OBJECTIVE: Literature reports bactericidal and biostimulant effects for Nd:YAG laser procedures on bone and oral mucosa but the possible overheating can cause damage to anatomical structures. The aim of the study was to evaluate the is the evaluation of thermal increase in different levels of oral tissues: mucosa, periosteum and bone during defocused application of Nd:YAG laser at different parameters. STUDY DESIGN: Superficial thermal evaluation was performed in pig jaws with a thermal camera device; deep thermal evaluation was realized by 4 thermocouples placed at a subperiosteal level and at 1,2 and 4 mm depth in the jaw bone. Laser applications of 1 minute were performed 5 times (with a pause of 1 minute) on a surface of 4 cm2 with a Nd:YAG laser (MSP mode, 320 micrometer fiber, defocused mode) with different parameters. Temperatures were recorded before and after laser applications and after each pause in order to evaluate also the thermal relaxation of tissues. RESULTS: At submucosal level, mean thermal increase was between 1.1 degrees C and 13.2 degrees C, at 1 mm depth between 1.1 degrees C and 8.5 degrees C, at 2 mm depth between 1.1 degrees C and 6.8 degrees C, at 4 mm depth between 1.0 degrees C and 5.3 degrees C. Temperature decrease during the rest time period was variable between 0 degrees C and 2.5 degrees C. CONCLUSIONS: Temperatures reached during clinical procedures with parameters reported in the literature in biostimulation protocols (1.25-2 Watts) for the five minutes of application are not dangerous for biological structures. The decrease in temperature during the rest time period is less considerable in the bone in comparison to oral mucosa. PMID- 22322507 TI - Oral lichenoid lesions associated with amalgam restorations: a prospective pilot study addressing the adult population of the Basque Country. AB - Oral lichenoid lesions (OLLs) are linked to a heterogeneous group of pathologies involving the oral mucosa that cannot be distinguished from the oral lichen planus excepting the fact that direct causal factors such as silver amalgam restorations (SARs) can be allocated to them. PURPOSE: To analyze the prevalence of mucosal lesions associated with SAR in a group of SAR carrying patients in the Basque Country. STUDY DESIGN: A clinical prospective study was carried out on 100 adult patients over 30 years of age at the UPV/EHU Clinical Odontology Service whose rear teeth had at least one SAR. Patients were identified and mucosal lesions and amalgam restorations were characterized. Patch tests were performed on patients with lesions and amalgams were replaced with composite material. A statistical and comparative analysis was performed with the resulting data. RESULTS: OLLs were found in 7 patients whose predominant lesion was bilateral, asymmetrical and asymptomatic white papule-macule. Lesions were related to old and corroded SARs. Patch testing was positive in two cases. SAR substitution produced an improvement in 5 cases. CONCLUSIONS: The presence of lichenoid lesions associated with SARs is infrequent in our environment and is preferentially related to old and corroded restorations. PMID- 22322508 TI - A pioneering epidemiological study investigating the incidence of squamous cell carcinoma of tongue in a Portuguese population. AB - OBJECTIVE: The purpose of this study was to investigate the incidence of squamous cell carcinoma (SCC) of the anterior two thirds of the tongue in a population living in central and southern Portugal, all treated at Instituto Portugues de Oncologia de Lisboa, Francisco Gentil (IPOLFG). STUDY DESIGN: This study was a retrospective review of all patients who had a histo- pathological diagnosis of SCC of the anterior two thirds of the tongue and had been treated in the Head and Neck Surgery Unit at the IPOLFG (Lisbon, Portugal), between 1st January 2001 and 31st December 2009. The risk factors evaluated were: gender; age; alcohol consumption; tobacco use; prosthesis use and the carcinoma site. RESULTS: Of the 424 cases analysed, 71% were men. Mean age of occurrence was in 5th decade for males and the 6th decade for females, and the border of the tongue was the most common location. Alcohol consumption and tobacco had a lower impact in women, being the most common aetiological factors in the male population. No significant association was observed between patients and the use of a prosthesis. CONCLUSIONS: In spite of the consumption of aohol and tobacco starting to decline in certain parts of the world, our findings showed both factors still have a significant impact in male population. Further research should be done to determine aetiological factors in females. PMID- 22322509 TI - Effect of bleaching agents on sealing properties of different intraorifice barriers and root filling materials. AB - OBJECTIVE: To evaluate the effect of intracoronal bleaching agents on the sealing properties of different intraorifice barriers and root filling materials. STUDY DESIGN: The root canals of extracted human premolars (n=180) were prepared by using System GT rotary files and filled with either gutta-percha+AH Plus or Resilon+Epiphany sealer. In both groups, the coronal 3mm of root filling was removed and replaced with one of the following materials applied as intraorifice barriers (n=30/group): 1. ProProot-MTA; 2. Conventional Glass ionomer cement; and 3. Hybrid resin composite. In each subgroup, intracoronal bleaching was performed using either sodium perborate with distilled water or 35% hydrogen peroxide gel for 3 weeks. The leakage of specimens was measured using fluid-filtration and dye penetration tests. The data were analyzed statistically with One-way ANOVA, Repeated Measures t-test and Independent Samples t-test (p=0.05). RESULTS: The fluid conductance values of the test groups were not influenced by the type of the bleaching agent, the intraorifice barrier, or the root filling material (all p>0.05). However, the extent of dye leakage was significantly affected by the type of intraorifice barrier material (p<0.05), which showed the following statistical ranking: glass ionomer cement > resin composite > ProRoot-MTA (p<0.05). CONCLUSIONS: The effect of 35% hydrogen peroxide gel or sodium perborate/distilled water on the sealing properties of tested intraorifice barriers and root filling materials varied conforming leakage assessment. These properties were not affected by using fluid filtration test, while the glass ionomer barrier showed the greatest amount of dye leakage in both gutta-percha and Resilon root-filled teeth. PMID- 22322510 TI - Pain and swelling after periapical surgery related to the hemostatic agent used: anesthetic solution with vasoconstrictor or aluminum chloride. AB - OBJECTIVE: To assess pain and swelling in the first 7 days after periapical surgery and their relationship with the agent used for bleeding control. STUDY DESIGN: A prospective study was conducted between October 2006 and March 2009. Patients subjected to root surgery, who completed the questionnaire and who consented to the postoperative instructions were included in the study. The subjects were divided into two groups according to the hemostatic agent used: A) gauze impregnated with anesthetic solution with vasoconstrictor; or B) aluminum chloride. The patients were administered a questionnaire, and were asked to record the severity of their pain and swelling on a plain horizontal visual analog scale (VAS). Data were recorded by the patients on the first 7 postoperative days. In addition, the patients were asked to record analgesic consumption. RESULTS: A total of 76 questionnaires (34 in group A and 42 in group B) were taken to be correctly completed. Pain was reported to be most intense two hours after surgery. At this point 52.6% of the patients had no pain. Seventy five percent of the patients consumed analgesics in the first 24 hours. There were no significant differences between the two groups in terms of the intensity of pain or in the consumption of analgesics. Swelling reached its maximum peak on the second day; at this point, 60.6% of the patients suffered mild or moderate swelling. The Expasyl group showed significantly greater swelling than the gauzes group. CONCLUSION: The type of hemostatic agent used did not influence either the degree of pain or the need for analgesia among the patients in this study. However, the patients belonging to the Expasyl group suffered greater swelling than the patients treated with gauzes impregnated with anesthetic solution with vasoconstrictor. PMID- 22322511 TI - Association between condylar asymmetry and temporomandibular disorders using 3D CT. AB - OBJECTIVES: Using reconstructed three-dimensional computed tomography (3D-CT) models, the purpose of this study was to analyze and compare mandibular condyle morphology in patients with and without temporomandibular disorder (TMD). STUDY DESIGN: Thirty-two patients were divided into two groups: the first comprised those with TMD (n=18), and the second those who did not have TMD (n=14). A CT of each patient was obtained and reconstructed as a 3D model. The 64 resulting 3D condylar models were evaluated for possible TMD-associated length, width and height asymmetries of the condylar process. Descriptive statistics were used to assess the results and student' s t tests applied to compare the two groups. RESULTS: Statistically significant (p<0.05) vertical, mediolateral and sagittal asymmetries of the condylar process were observed between TMD and non-TMD groups. TMD patients showed less condylar height (p<0.05) in comparison with their asymptomatic counterparts. CONCLUSIONS: Using 3D-CT, it was shown that condylar width, height and length asymmetries were a common feature of TMD. PMID- 22322512 TI - Epiphany root canal sealer prepared with resinous solvent is irritating to rat subcutaneous tissues. AB - OBJECTIVE: This study assessed the biocompatibility of the Epiphany endodontic sealer prepared with resinous solvent of Epiphany system (Thinning resin) in rat subcutaneous tissues. STUDY DESIGN: Polyethylene tubes were filled with the sealer and 4 groups were established: GI, Epiphany prepared with 1 drop of resinous solvent (RS); GII, Epiphany prepared with 1 drop of RS and photoactivated; GIII, Epiphany associated with self-etch primer and prepared with 1 drop of RS; GIV, Epiphany associated with self-etch primer, prepared with 1 drop of RS and photoactivated. The filled tubes were implanted into 4 different regions of the dorsum of 20 adult male rats. RESULTS: After 7, 14 and 21 days, all groups presented a moderate to severe chronic inflammation, necrosis and foreign-body giant cells. At 42 days, although the intensity of chronic inflammatory reaction decreased, the other features still were observed. CONCLUSION: The Epiphany sealer prepared with the RS was irritating to rat subcutaneous tissues. PMID- 22322513 TI - Efect of periodontal disease and non surgical periodontal treatment on C-reactive protein. Evaluation of type 1 diabetic patients. AB - OBJECTIVES: The purpose of this study was to analyze how anti-infectious periodontal treatment affects C reactive protein (CRP) values in patients with type 1 diabetes, and correlate baseline CRP levels with periodontal disease severity. STUDY DESIGN: A cohort of fifty three subjects with type 1 diabetes and moderate to severe periodontitis were recruited. Periodontal parameters were measured, and blood samples were obtained to evaluate high-sensitivity C-reactive protein (hs-CRP). Group 1 was treated with scaling, root planning, and systemic administration of doxycycline. Group 2 received only scaling and root planning. RESULTS: Hs-CRP was reduced after periodontal treatment in group 1 (-0.22 mg/l) and 2 (-0.21 mg/l ) but this reduction was not statistically significant, even in the patients with the best response to periodontal treatment. However, significant correlation appeared between hs-CRP and mean probing pocket depth (PPD) (p=0, 01) and mean clinical attachment level (CAL) (p=0,03). CONCLUSIONS: Non-surgical periodontal treatment couldn' t reduce hs-CRP values, however, it was found an association between advanced periodontitis and elevated blood hs-CRP levels in patients with type 1 diabetes. It can be speculated that periodontal disease increases production of pro-inflammatory mediators in patients with type 1 diabetes, but other producing sources of these pro-inflammatory substances may exist. PMID- 22322514 TI - Microhardness of different resin cement shades inside the root canal. AB - OBJECTIVES: To compare microhardness along the root canal post space of two resin cements in different shades and a dual-cure resin core material. STUDY DESIGN: Root canals of 21 bovine incisors were prepared for post space. Translucent posts (X?Post, Dentsply DeTrey) were luted using one the following resin luting agent: Calibra (Dentsply DeTrey) in Translucent, Medium and Opaque shades, RelyX Unicem (3M ESPE) in Translucent, A2 and A3 shades and the dual-cure resin core material Core?X flow. All materials were applied according to manufacturers' instructions and were all photopolymerized (Bluephase LED unit, Ivoclar Vivadent, 40s). After 24 hours, roots were transversally cut into 9 slices 1 mm thick from the coronal to apical extremes, three corresponding to each root third. Then, VHNs were recorded (100gf, 30 s) on the resin luting materials along the adhesive interface in all sections. Data were analyzed by two-way ANOVA and SNK tests (alpha=0.05). RESULTS: A significant influence on microhardness of resin luting material in their respective shades (p<0.0001), root third (p<0.0001) and interactions between them was detected (p<0.0001). RelyX Unicem cement showed the highest microhardness values and Calibra the lowest, regardless of the shade selected. All resin luting materials tested exhibited a significantly higher microhardness in the cervical third. CONCLUSIONS: Microhardness of resin luting agents tested inside the canal is dependent on material brand and resin cement shade seems to be a less relevant factor. Microhardness decreased along the root canal, regardless of the shade selected. PMID- 22322515 TI - Clinical and histological features of gingival lesions: a 17-year retrospective analysis in a northern Italian population. AB - OBJECTIVES: Only few studies on gingival lesions considered large enough populations and contemporary literature does not provide a valid report regarding the epidemiology of gingival lesions within the Italian population. The histopathological and clinical appearance of 538 gingival lesions from northern Italians are described and discussed here. STUDY DESIGN: The case records of patients referred for the diagnosis and management of gingival lesions, from October 1993 to October 2009, were reviewed. Data regarding the histological type of lesion were also obtained from the biopsy register for each case, and blindly re-examined. RESULTS: We reported a greater frequency of benign lesions (reactive and/or inflammatory) in non-plaque/non-calculus induced gingival disorders. We confirmed an unambiguous prevalence of oral squamous cell carcinoma above all other malignant neoplasia, and a prevalence of neoplastic malignant lesions in the maxilla, with a slight increase in females and a drift of the incidence peak from the seventh to the eighth decade. There was a prevalence of precancerous gingival lesions in the maxilla, with a higher incidence in females and with a drift from the sixth to the seventh decade. We also reported a prevalence of oral lichen planus and lichenoid lesions as major manifestations of desquamative gingivitis. CONCLUSIONS: The high frequency of gingival involvement of such different diseases emphasizes the importance of histological characterization and differential diagnosis for periodontists, but more prospective studies are needed to better describe the true incidence of the non-plaque related gingival diseases. PMID- 22322516 TI - Changes in nasal air flow and school grades after rapid maxillary expansion in oral breathing children. AB - OBJECTIVE: To analyse the changes in nasal air flow and school grades after rapid maxillary expansion (RME) in oral breathing children with maxillary constriction. MATERIAL AND METHODS: Forty-four oral breathing children (mean age 10.57 y) underwent orthodontic RME with a Hyrax screw. Forty-four age-matched children (mean age 10.64 y) with nasal physiological breathing and adequate transverse maxillary dimensions served as the control group. The maxillary widths, nasal air flow assessed via peak nasal inspiratory flow (PNIF), and school grades were recorded at baseline, and 6 months and one year following RME. RESULTS: After RME, there were significant increases in all the maxillary widths in the study group. PNIF was reduced in the study group (60.91+/-13.13 l/min) compared to the control group (94.50+/-9.89 l/min) (P<0.000) at the beginning of the study. Six months after RME, a significant improvement of PNIF was observed in the study group (36.43+/-22.61). School grades were lower in the study group (85.52+/-5.74) than in the control group (89.77+/-4.44) (P<0.05) at the baseline, but it increased six months after RME (2.77+/-3.90) (P<0.001) and one year later (5.02+/ 15.23) (P<0.05). CONCLUSIONS: Nasal air flow improved in oral breathing children six months and one year after RME. School grades also improved, but not high enough to be academically significant. PMID- 22322517 TI - Resistance to bond degradation between dual-cure resin cements and pre-treated sintered CAD-CAM dental ceramics. AB - OBJECTIVE: To evaluate the bond stability of resin cements when luted to glass reinforced alumina and zirconia CAD/CAM dental ceramics. STUDY DESIGN: Eighteen glass-infiltrated alumina and eighteen densely sintered zirconia blocks were randomly conditioned as follows: Group 1: No treatment; Group 2: Sandblasting (125 um Al2O3-particles); and Group 3: Silica-coating (50 um silica-modified Al2O3-particles). Composite samples were randomly bonded to the pretreated ceramic surfaces using different resin cements: Subgroup 1: Clearfil Esthetic Cement (CEC); Subgroup 2: RelyX Unicem (RXU); and Subgroup 3: Calibra (CAL). After 24 h, bonded specimens were cut into 1 +/- 0.1 mm2 sticks. One-half of the beams were tested for microtensile bond strength (MTBS). The remaining one-half was immersed in 10 % NaOCl aqueous solution (NaOClaq) for 5 h before testing. The fracture pattern and morphology of the debonded surfaces were assessed with a field emission gun scanning electron microscope (FEG-SEM). A multiple ANOVA was conducted to analyze the contributions of ceramic composition, surface treatment, resin cement type, and chemical challenging to MTBS. The Tukey test was run for multiple comparisons (p < 0.05). RESULTS: After 24 h, CEC luted to pre-treated zirconia achieved the highest MTBS. Using RXU, alumina and zirconia registered comparable MTBS. CAL failed prematurely, except when luted to sandblasted zirconia. After NaOClaq storage, CEC significantly lowered MTBS when luted to zirconia or alumina. RXU decreased MTBS only when bonded to silica-coated alumina. CAL recorded 100 % of pre-testing failures. Micromorphological alterations were evident after NaOClaq immersion. CONCLUSIONS: Resin-ceramic interfacial longevity depended on cement selection rather than on surface pre treatments. The MDP-containing and the self-adhesive resin cements were both suitable for luting CAD/CAM ceramics. Despite both cements being prone to degradation, RXU luted to zirconia or untreated or sandblasted alumina showed the most stable interfaces. CAL experimented spontaneous debonding in all tested groups. PMID- 22322518 TI - Stromal myofibroblasts in oral leukoplakia and oral squamous cell carcinoma. AB - OBJECTIVES: Oral leukoplakia (OL) is the main potentially malignant disorder and oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral mucosa. Stromal myofibroblasts play an important role in tumor invasion and metastasis, due to its ability to modify the extracellular matrix. This study aimed to evaluate the presence of stromal myofibroblasts in OL and OSCC. Differences in the presence of myofibroblasts among OL with distinct grades of epithelial dysplasia as well as between histologically high- and low-invasive OSCC were also assessed. STUDY DESIGN: A total of 30 OL and 41 OSCC from archival formalin-fixed, paraffin-embedded specimens were evaluated. 10 samples of normal oral mucosa were used as a control. Myofibroblasts were identified by immunohistochemical detection of alpha smooth muscle actin and its presence was classified as negative, scanty or abundant. Differences in the presence of myofibroblasts among OL with distinct grades of epithelial dysplasia as well as between high- and low-invasive OSCC were analyzed using the Mann-Whitney test. RESULTS: Myofibroblasts were not detected in normal oral mucosa and OL, whatever its histological grade. In OSCC, the presence of stromal myofibroblasts was classified as negative in 11 (26.8%), scanty in 15 (36.6%), and abundant in 15 samples (36.6%). The presence of stromal myofibroblasts was statistically higher in high-invasive OSCC than in low-invasive OSCC (p<0.05). CONCLUSIONS: Stromal myofibroblasts were not detected in OL, indicating that these cells are not important during oral carcinogenesis. Nevertheless, stromal myofibroblasts were heterogeneously detected in OSCC and its presence was higher in tumors with a more diffuse histological pattern of invasion. These findings suggest that myofibroblasts are associated with the creation of a permissive environment for tumor invasion in OSCC. PMID- 22322519 TI - Resonance frequency analysis-reliability in third generation instruments: Osstell mentor(r). AB - Few studies assess repeatability and reproducibility in registers of resonance frequency analysis (a value of dental implant stability). OBJECTIVE: Few studies assess repeatability and reproducibility in resonance frequency analyses (implant stability evaluation). This study is aimed at assessing reliability (repeatabilty and reproducibility) in the Osstell Mentor(r) system using the intraclass correlation coefficient (ICC) as the statistical method. STUDY DESIGN: ISQ measurements of RFA were carried out by means of the Osstell Mentor(r) instrument in 58 implants in 19 patients. Six measurements were performed on each implant by means of two different Smart-Pegs (I and II). Three consecutive measurements were registered with each transducer. RESULTS: Average ISQ varied from 72.43 to 72.60 and 73.26 in the first, second and third measurements, respectively with the SamrtPeg I and from 72.98 to 73.26 and 73.74 in the first, second and third measurements, respectively with the SamrtPeg II . Exactly equal values were observed in 10.43 and 12.1% of the cases with Smart-Pegs I and II, respectively. The intraclass correlation coefficient was 0.96 and 0.96 for Smart Pegs I and II, respectively. Repeatability and reproducibility was 0.97 for both Smart-Pegs I and II. CONCLUSIONS: The RFA system contributed by Osstell Mentor(r) renders almost perfect reproducibility and repeatability, as proven by statistical analysis carried out by means of ICC with 95% confidence level. This instrument contributes highly reliable RFA measurements in dental implants. PMID- 22322520 TI - Sensibility and taste alterations after impacted lower third molar extractions. A prospective cohort study. AB - OBJECTIVES: To determine the incidence, severity and duration of lingual tactile and gustatory function impairments after lower third molar removal. STUDY DESIGN: Prospective cohort study with intra-subject measures of 16 patients undergoing lower third molar extractions. Sensibility and gustatory functions were evaluated in each subject preoperatively, one week and one month after the extraction, using Semmes-Weinstein monofilaments and 5 different concentrations of NaCl, respectively. Additionally, all patients filled a questionnaire to assess subjective perceptions. RESULTS: Although patients did not perceive any sensibility impairments, a statistically significant decrease was detected when Semmes-Weinstein monofilaments. This alteration was present at one week after the surgical procedure and fully recovered one month after the extraction. There were no variations regarding the gustatory function. CONCLUSIONS: Lower third molar removal under local anesthesia may cause light lingual sensibility impairment. Most of these alterations remain undetected to patients. These lingual nerve injuries are present one week after the extraction and recover one month after surgery. The taste seems to remain unaffected after these procedures. PMID- 22322521 TI - Cardiovascular effect of dental anesthesia with articaine (40 mg with epinefrine 0,5 mg % and 40 mg with epinefrine 1 mg%) versus mepivacaine (30 mg and 20 mg with epinefrine 1 mg%) in medically compromised cardiac patients: a cross-over, randomized, single blinded study. AB - OBJECTIVES: The aim of the present study is to compare cardiovascular safety profiles of two dental anesthetics: articaine versus two standard mepivacaine solutions used during etiological periodontal treatment in cardiovascular patients. STUDY DESIGN: Using a cross-over study design, ten cardiovascular patients were randomly assigned to dental treatment with 1.8 mL of a local anesthetic injected on each quadrant of the mouth: Articaine (40 mg with Epinephrine 0.5 mg % and 40 mg with Epinephrine 1mg %) or Mepivacaine (30 mg and 20 mg with Epinephrine 1mg %). A computer programme enabled continuous longitudinal data collection: O2 saturation, blood pressure (BP) and heart rate (HR). RESULTS: No severe clinical side effects were observed. During the treatment period, we observed statistically significant differences as regards HR between injections with and without adrenalin (p< 0.039) and as regards systolic (p< 0.046) and diastolic (p < 0.046) blood pressure during the stabilization period. In both cases, the parameters under study increase. Age, gender, jaw treated, treatment duration and the rest of cardiovascular variables did not affect the results. None of the patients underwent ischemic alterations or any other complication derived from the treatment or the anesthesia. CONCLUSIONS: According to the results of our study, dental anesthetics with standard concentrations of Epinephrine seem to alter HR and BP. Although no cardiac ischemic alterations or any other cardiovascular complications have been observed, we must be cautious with the administration of anesthetics containing vasoconstrictors in patients with cardiovascular diseases. PMID- 22322522 TI - Postoperative pain after one-visit root-canal treatment on teeth with vital pulps: comparison of three different obturation techniques. AB - OBJECTIVES: To investigate and compare postoperative pain after one-visit root canal treatment (RCT) on teeth with vital pulps using three different obturation techniques. STUDY DESIGN: Two hundred and four patients (105 men and 99 women) aged 12 to 77 years were randomly assigned into three treatments groups: cold lateral compaction of gutta-percha (LC), Thermafil technique (TT), and Backfill - Thermafil obturation technique (BT). Postoperative pain was recorded on a visual analogue scale (VAS) of 0 - 10 after 2 and 6 hours, and 1, 2, 3, 4, 5, 6 and 7 days. Data were statistically analyzed using multivariate logistic regression analysis. RESULTS: In the total sample, 87% of patients experienced discomfort or pain in some moment between RCT and the seventh day. The discomfort experienced was weak, light, moderate and intense in 6%, 44%, 20% and 6% of the cases, respectively. Mean pain levels were 0.4 +/- 0.4, 0.4 +/- 0.3, and 1.4 +/- 0.7 in LC, BT, and TT groups, respectively. Patients of TT group experienced a significantly higher mean pain level compared to other two groups (p < 0.0001). In TT group, all patients felt some level of pain at six hours after RCT. CONCLUSIONS: Postoperative pain was significantly associated with the obturation technique used during root canal treatment. Patients whose teeth were filled with Thermafil obturators (TT technique) showed significantly higher levels of discomfort than patients whose teeth were filled using any of the other two techniques. PMID- 22322523 TI - Immunohistochemical expression of EGFR in oral leukoplakia: association with clinicopathological features and cellular proliferation. AB - OBJECTIVES: To investigate the immunoexpression of epidermal growth factor receptor (EGFR) in a sample of oral leukoplakias (OL) and to determine the receptor' s association with dysplasia, tobacco consumption, lesion site, and proliferation rate. Although EGFR should be overexpressed in some oral leukoplakias, the factors that may interfere with this expression and the influence of this receptor on epithelial proliferation have yet to be investigated. STUDY DESIGN: Samples of oral leukoplakias (48) and of normal oral epithelium (10) were immunohistologically examined for expression of EGFR. Immunohistochemistry for Ki-67, and p27 were also performed in leukoplakias. EGFR expression was associated with clinical and pathological features. RESULTS: EGFR was positive in 62.5% of the leukoplakias and 50% of normal oral epithelium. The number of EGFR positive OL located in high-risk sites was significantly higher than EGFR positive OL located in low-risk sites. Most of the p27 negative leukoplakias were EGFR positive, and the p27 index in the parabasal layer was diminished in the presence of dysplasia. Positivity for EGFR was not associated with dysplasia, tobacco exposure, or Ki-67. CONCLUSION: EGFR is expressed in leukoplakia regardless of dysplasia, but EGFR positivity should be more frequent in lesions sited in areas of high cancer risk. The association between EGFR and p27 may represent an important mechanism in the control of cellular proliferation and malignant progression of oral epithelium and therefore warrants further investigation. PMID- 22322524 TI - Vertical misfit of laser-sintered and vacuum-cast implant-supported crown copings luted with definitive and temporary luting agents. AB - OBJECTIVES: This study aimed to evaluate the vertical discrepancy of implant supported crown structures constructed with vacuum-casting and Direct Metal Laser Sintering (DMLS) technologies, and luted with different cement types. STUDY DESIGN: Crown copings were fabricated using: (1) direct metal laser sintered Co Cr (LS); (2) vacuum-cast Co-Cr (CC); and (3) vacuum-cast Ti (CT). Frameworks were luted onto machined implant abutments under constant seating pressure. Each alloy group was randomly divided into 5 subgroups (n = 10 each) according to the cement system utilized: Subgroup 1 (KC) used resin-modified glass-ionomer Ketac Cem Plus; Subgroup 2 (PF) used Panavia F 2.0 dual-cure resin cement; Subgroup 3 (RXU) used RelyX Unicem 2 Automix self-adhesive dual-cure resin cement; Subgroup 4 (PIC) used acrylic/urethane-based temporary Premier Implant Cement; and Subgroup 5 (DT) used acrylic/urethane-based temporary DentoTemp cement. Vertical misfit was measured by scanning electron microscopy (SEM). Two-way ANOVA and Student Newman-Keuls tests were run to investigate the effect of alloy/fabrication technique, and cement type on vertical misfit. The statistical significance was set at alpha = 0.05. RESULTS: The alloy/manufacturing technique and the luting cement affected the vertical discrepancy (p < 0.001). For each cement type, LS samples exhibited the best fit (p < 0.01) whereas CC and CT frames were statistically similar. Within each alloy group, PF and RXU provided comparably greater discrepancies than KC, PIC, and DT, which showed no differences. CONCLUSIONS: Laser sintering may be an alternative to vacuum-casting of base metals to obtain passive-fitting implant-supported crown copings. The best marginal adaptation corresponded to laser sintered structures luted with glass ionomer KC, or temporary PIC or DT cements. The highest discrepancies were recorded for Co-Cr and Ti cast frameworks bonded with PF or RXU resinous agents. All groups were within the clinically acceptable misfit range. PMID- 22322525 TI - Preparation of chiral amino esters by asymmetric phase-transfer catalyzed alkylations of Schiff bases in a ball mill. AB - The asymmetric alkylation of Schiff bases under basic conditions in a ball mill was performed. The starting Schiff bases of glycine were prepared beforehand by milling protected glycine hydrochloride and benzophenone imine, in the absence of solvent. The Schiff base was then reacted with a halogenated derivative in a ball mill in the presence of KOH. By adding a chiral ammonium salt derived from cinchonidine, the reaction proceeded asymmetrically under phase-transfer catalysis conditions, giving excellent yields and enantiomeric excesses up to 75 %. Because an equimolar amount of starting material was used, purification was greatly simplified. PMID- 22322526 TI - A meta-analysis and systematic review of computed tomography angiography as a diagnostic triage tool for patients with chest pain presenting to the emergency department. AB - BACKGROUND: To assess clinical utility of computed tomography angiography (CTA) in the diagnosis of chest pain patients presenting to emergency departments (EDs), we conducted a meta-analysis of CTA in patients with suspected acute coronary syndromes (ACSs). METHODS: 386 studies were identified on initial review of literature. Inclusion criteria were: (1) prospective study with >=1 month follow-up, (2) use of CTA in the ED setting, (3) use of ACC/AHA definitions for ACS and robust assessment of major adverse cardiac events, (4) >=30 patients, and (5) study population with initial non-diagnostic ECGs and negative biomarkers. RESULTS: Nine studies (N = 1349) formed the data set. The pooled patient population was 52 +/- 2 years of age, 51% male, with low to intermediate pretest probability for ACS. Risk factors included 12% diabetes, 42% hypertension, 35% smokers, 29% had hyperlipidemia, and 7% known CAD. ACS was subsequently diagnosed in 10% of patients. The bivariate summary estimate of sensitivity of CTA for ACS diagnosis was 95% (95% CI 88-100) and specificity was 87% (95% CI 83-92), yielding a negative likelihood ratio of 0.06 (95% CI 0-0.14) and positive likelihood ratio of 7.4 (95% CI 4.8-10). The 30-day event rate included no deaths and no additional MIs. CONCLUSION: Coronary CTA demonstrates a high sensitivity and a low negative likelihood ratio of 0.06, and is effective in ruling out the presence of ACS in low to intermediate risk patients presenting to the ED with acute chest pain. PMID- 22322527 TI - Biodegradation of semiconductor volatile organic compounds by four novel bacterial strains: a kinetic analysis. AB - This study isolated pure microorganisms for further bioreactor applications. Four novel strains of Pseudomonas citronellolis YAIP521, Paracoccus versutus HSAC51, Burkholderia sp. HUEL671, and Pseudomonas aeruginosa JUPG561 were isolated and tested for biodegradation of isopropyl alcohol (IPA), acetone, ethyl lactate (EL), and propylene glycol mono methyl ether acetate (PGMEA), respectively. The maximum biodegradation rates for IPA, acetone, EL, and PGMEA were 5.27, 3.87, 26.86, and 48.93 mg L(-1) h(-1), respectively. The Haldane kinetic parameters determined for these strains when degrading targeted volatile organic compounds were maximum specific growth rate, half-saturation constant, and inhibition constant. The isolated strains have potential application in various bioreactors. The kinetic parameters obtained in this study provide a basis for further bioreactor experiments. PMID- 22322528 TI - Relative deficiency of acidic isoforms of osteopontin from stone former urine. AB - We have tested the relative electrophoretic mobility of osteopontin (OPN) isolated from urine obtained from normal individuals (NU) against similar samples derived from the urine of stone formers (SFU) using high-resolution isoelectric focusing (isoelectric point, pI range 3.5-4.5) in 2D electrophoresis, with Western blot detection. We also report the results from competitive ELISA analyses of these samples. We demonstrated that human urinary OPN has a discrete four band separation pattern that conforms to four previously documented OPN isoforms. The lower two M(r) isoforms migrate to a greater degree toward the acidic end of the gel than do the higher two M(r) isoforms. Densitometry of the signal reveals significant difference in the migration pattern of OPN from SFU as compared to that from NU based on an analysis of the spot intensities grouped in 0.1 pI unit increments. A novel method for the calculation of a weight-averaged pI based on the relative signal strength in an OPN 2D Western blot was developed. The analysis revealed a significantly increased weight-averaged pI values for the higher M(r) forms of OPN in the stone former compared to normal population. Additionally, alkaline phosphatase-treated NU samples resulted in a significant average pI shift of 0.05 units in the alkaline direction, suggesting that a decrease in the average degree of phosphorylation could be responsible for the difference between NU and SFU pI. PMID- 22322529 TI - Tgf-beta1 induces autophagy and promotes apoptosis in renal tubular epithelial cells. AB - Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that regulates cell growth, differentiation, apoptosis and autophagy in various cell types. It has been shown that TGF-beta1-driven autophagy represents a novel mechanism of tubular decomposition, leading to renal interstitial fibrosis. However, the exact mechanism by which TGF-beta1 regulates autophagy is still poorly understood. In the present study, we investigated the effects of exogenous TGF-beta1 on cultured human renal proximal tubular epithelial cells (HRPTEpiCs). Presence of TGF-beta1 in the medium induced accumulation of autophagosomes in a time- and dose-dependent manner as seen by monitoring the marker LC3 by confocal fluorescence microscopy and immunoblotting. In addition, TGF-beta1 induced upregulation of autophagy-related genes, Atg5, Atg7 and Beclin1. Importantly, increased generation of reactive oxygen species (ROS) and enhanced expression of NADPH oxidases were found to be associated with the TGF-beta1-induced autophagy. Conversely, treatment with inhibitors of NADPH oxidase markedly reversed the autophagic effects of TGF-beta1. Apoptotic effects were evaluated by the TUNEL assay, measuring mitochondrial membrane potential and monitoring expression of the pro- and anti-apoptotic genes, Bim and Bcl-2, respectively. Transcriptional silencing of the above three autophagy-related genes in HRPTEpiCs caused attenuation of TGF-beta1-mediated apoptosis. Similarly, when autophagy was prevented at an early stage by application of 3-methyladenine, the pro-apoptotic effects of TGF-beta1 were attenuated. These observations suggest that in HRPTEpiCs TGF-beta1 promotes autophagy through the generation of ROS, which contributes to its proapoptotic effect. PMID- 22322530 TI - 3D branched nanowire heterojunction photoelectrodes for high-efficiency solar water splitting and H2 generation. AB - We report the fabrication of a three dimensional branched ZnO/Si heterojunction nanowire array by a two-step, wafer-scale, low-cost, solution etching/growth method and its use as photoelectrode in a photoelectrochemical cell for high efficiency solar powered water splitting. Specifically, we demonstrate that the branched nanowire heterojunction photoelectrode offers improved light absorption, increased photocurrent generation due to the effective charge separation in Si nanowire backbones and ZnO nanowire branching, and enhanced gas evolution kinetics because of the dramatically increased surface area and decreased radius of curvature. The branching nanowire heterostructures offer direct functional integration of different materials for high efficiency water photoelectrolysis and scalable photoelectrodes for clean hydrogen fuel generation. PMID- 22322532 TI - Surgical treatment of colorectal cancer in patients aged over 80 years. AB - PURPOSE: The aim of this study was to identify the clinical factors and tumour characteristics that predict the outcome in patients older than 80 years with colorectal cancer. PATIENTS AND METHODS: One hundred and four patients with colorectal cancer aged over 80 years were identified from a computer database, and their clinical variables were analysed by both univariate and multivariate analyses. RESULTS: All 104 patients underwent resective surgery, 87% radical and 13% palliative resection. Postoperative mortality was 5%, being associated with a number of coexisting diseases and the presence of postoperative complications, especially anastomotic leakage. The cumulative 5-year survival was 33%, the median survival was 31 months and the cancer-specific 5-year survival was 36%. The recurrence rate after radical surgery was 30%, being 13%, 25%, 44% and 100% in the Union for International Cancer Control stages I, II, III and IV. Kaplan Meier estimates indicated that age, number of underlying diseases, radicality of operation, Dukes' staging, size of tumour, number of lymph node metastasis, metastasised disease, venous invasion and recurrent disease were significant predictors of survival, but in the Cox regression model, only venous invasion was an independent prognostic factor of survival. CONCLUSIONS: Low mortality and acceptable survival can be achieved even in very elderly patients with colorectal cancer. Venous invasion is an independent predictor of survival. PMID- 22322531 TI - Preoperative serum brain natriuretic peptide and risk of acute kidney injury after cardiac surgery. AB - BACKGROUND: Acute kidney injury (AKI) after cardiac surgery is associated with poor outcomes and is difficult to predict. We conducted a prospective study to evaluate whether preoperative brain natriuretic peptide (BNP) levels predict postoperative AKI among patients undergoing cardiac surgery. METHODS AND RESULTS: The Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury (TRIBE-AKI) study enrolled 1139 adults undergoing cardiac surgery at 6 hospitals from 2007 to 2009 who were selected for high AKI risk. Preoperative BNP was categorized into quintiles. AKI was common with the use of Acute Kidney Injury Network definitions; at least mild AKI was a >=0.3-mg/dL or 50% rise in creatinine (n=407, 36%), and severe AKI was either a doubling of creatinine or the requirement of acute renal replacement therapy (n=58, 5.1%). In analyses adjusted for preoperative characteristics, preoperative BNP was a strong and independent predictor of mild and severe AKI. Compared with the lowest BNP quintile, the highest quintile had significantly higher risk of at least mild AKI (risk ratio, 1.87; 95% confidence interval, 1.40-2.49) and severe AKI (risk ratio, 3.17; 95% confidence interval, 1.06-9.48). After adjustment for clinical predictors, the addition of BNP improved the area under the curve to predict at least mild AKI (0.67-0.69; P=0.02) and severe AKI (0.73-0.75; P=0.11). Compared with clinical parameters alone, BNP modestly improved risk prediction of AKI cases into lower and higher risk (continuous net reclassification index; at least mild AKI: risk ratio, 0.183; 95% confidence interval, 0.061-0.314; severe AKI: risk ratio, 0.231; 95% confidence interval, 0.067-0.506). CONCLUSIONS: Preoperative BNP level is associated with postoperative AKI in high-risk patients undergoing cardiac surgery. If confirmed in other types of patients and surgeries, preoperative BNP may be a valuable component of future efforts to improve preoperative risk stratification and discrimination among surgical candidates. PMID- 22322533 TI - Raloxifene inhibits menin-dependent estrogen receptor activation in breast cancer cells. AB - BACKGROUND: Menin is a tumor suppressor encoded by Men1 that is mutated in the human-inherited tumor syndrome--multiple endocrine neoplasia type 1. Menin binds to estrogen receptors (ER) to enhance estrogen activity in breast cancer cells. AIM: Our clinical study showed that the outcome in the case of menin-positive tumors was worse than in the case of menin-negative tumors. We examined the role of raloxifene on the cell growth in a menin-positive breast cancer cell line. MATERIAL AND METHODS: To examine the mechanism of raloxifene on menin-dependent activation of ER, we employed the mammalian two-hybrid system. We have established a breast cancer cell line that stably expresses menin. Using these cells, we have examined the effect of raloxifene and tamoxifen on cell growth of menin-transfected cells. RESULTS: The expression of activation function (AF)-2 enhanced menin-mediated luciferase expression in the mammalian two-hybrid assay. Raloxifene attenuated the effect of menin on estrogen response element-luciferase activation, indicating that raloxifene inhibited the binding of menin to AF-2. Raloxifene significantly inhibited the growth of menin-transfected cells in a dose-dependent manner. Tamoxifen also inhibited menin-transfected MCF-7 cells; however, this inhibition was much less than that of raloxifene. CONCLUSION: Raloxifene inhibits the binding of menin to the AF-2 domain of ERalpha, suggesting that raloxifene is one of the therapeutic options for menin-positive breast cancer. PMID- 22322534 TI - The exon 3-deleted growth hormone receptor: molecular and functional characterization and impact on GH/IGF-I axis in physiological and pathological conditions. AB - The GH receptor (GHR) plays a key role in the the function of the GH/IGF-I axis and is the major effector of human growth. A common polymorphic variant consisting of genomic exon 3 deletion or retention (d3-GHR and full-length GHR, respectively), described in 2000, has been linked with increased receptor activity due to enhanced signal transduction. Subsequent pharmacogenetic studies have addressed a possible role of GHR polymorphism on the response to recombinant human GH treatment first in short children and then in adults, many of them suggesting that growth response to GH may be influenced, at least in some aspects, by this polymorphism. Similar studies, performed in patients with acromegaly, assumed an influence of the d3- GHR variant in the relationship between GH and IGF-I levels. More recently, some studies have investigated the relation between GHR genotype and treatment with the GHR antagonist pegvisomant, suggesting a better clinical response to therapy related to d3-GHR genotype. This review provides a summary of the main pharmacogenetic studies performed on this current and still open topic. PMID- 22322535 TI - Dose of intravenous steroids and therapy outcome in Graves' orbitopathy. AB - BACKGROUND AND AIM: Several trials have proved the efficacy of intravenous (IV) steroids in Graves' orbitopathy (GO). However, the impact of administered dose and therapy schedule has not been assessed yet. SUBJECTS AND METHODS: Nine randomized and 14 non-randomized controlled trials of IV steroids in GO were evaluated according to the applied single and cumulative doses with respect to outcome, efficacy on clinically relevant issues and adverse events. RESULTS: High single (1 g per day) and cumulative (>6 g) doses of IV steroids are superior to lower single (0.5 g/d) and cumulative (<5 g) doses with respect to therapy response (84 vs 75%; p=0.034 and 83 vs 77%; ns, respectively), improvement of eye symptoms (87 vs 75%, p=0.052 and 85 vs 71%; ns, respectively) and disappearance of diplopia (32 vs 27%; ns and 48 vs 27%; p=0.08, respectively). Decrease of both clinical activity score (3 vs 2.5 points and 2.5 vs 3, ns) as well as proptosis ( 1.4 vs -1.2 mm, ns and 1.5 vs 1.2, ns) are similar in both groups. However, high single and/or cumulative doses are accompanied with a 2-fold higher rate of adverse events (56 vs 28%; p<0.001 and 52 vs 33%; p=0.034, respectively). CONCLUSIONS: Tailoring the IV steroid dose to severity of GO can be concluded and implies that a prospective randomized trial comparing different doses of IV steroids in active/severe GO is keenly warranted. PMID- 22322536 TI - The role of serum uric acid in cardiovascular disease in type 2 diabetic and non diabetic subjects: a narrative review. AB - The role of serum uric acid (UA) as a marker or risk factor of cardiovascular disease (CVD) is still controversial. The strong association of serum UA with established risk factors such as hypertension, Type 2 diabetes, dyslipidemia, and chronic kidney disease makes it difficult to establish a direct causal role of serum UA in the development and progression of CVD. The main aims of this review are: 1) to briefly summarize the most relevant studies concerning the association of serum UA with hypertension, chronic kidney disease, CVD events, and death both in patients without diabetes and in those with Type 2 diabetes; and 2) to briefly discuss the putative underlying mechanisms that link serum UA to adverse CVD outcomes. A search was conducted to identify relevant studies in the major electronic databases (MEDLINE and EMBASE, from January 1990 to December 2010) using Medical Subjects Headings and keywords. Collectively, by reviewing the published data in the literature, it emerges that serum UA may exert a number of potentially adverse cardiovascular effects. Nevertheless, the prognostic role of elevated serum UA level as a causal risk factor of adverse CVD outcomes remains still controversial, especially in patients with Type 2 diabetes. At this time, the treatment of asymptomatic hyperuricemia for the primary prevention of CVD is not recommended. PMID- 22322537 TI - Cytological diagnosis difficulties in hyalinizing trabecular adenoma of the thyroid. PMID- 22322538 TI - Variable clinical presentations in a family with neurohypophysial diabetes insipidus. PMID- 22322539 TI - Endocrinology and art. Angelic hierarchies: domination--Guariento di Arpo (Padua- Notice 1338-1370). PMID- 22322540 TI - Frequency of fibromyalgia syndrome in breast cancer patients. AB - BACKGROUND: We aimed to determine the frequency of fibromyalgia syndrome (FM) in operated breast cancer patients and to research the relationship between FM and the severity of fatigue and quality of life in these breast cancer patients. METHODS: The demographic data of 101 operated breast cancer patients were recorded. The patients who had pain were then classified as having regional pain (RP), widespread pain without FM (WP), and widespread pain with FM (WFM). The FM diagnosis was based on the American College of Rheumatology (ACR) criteria. The severity of fatigue was evaluated with the Brief Fatigue Inventory, the disease impact was evaluated with the Fibromyalgia Impact Questionnaire (FIQ), and the quality of life was evaluated with the European Organization for Research on Treatment of Cancer questionnaire Quality of Life-C30 (EORTC-QoL-C30). RESULTS: There was no pain in 38 (37.6%) patients, whereas there was pain in 63 (62.4%) patients (N = 42, 41.6% had RP, N = 21, 20.8% had WP). Ten (9.9%) of the entire patient cohort were diagnosed as having FM according to the ACR criteria. There were no differences among the 3 groups in respect to demographic characteristics when patients were classified as RP (N = 42), WP (N = 11), and WFM (N = 10) groups. While there were negative correlations between the FIQ and EORTC-QoL-C30 function score (r = -0.727) and EORTC-QoL-C30-global score (r = -0.488), there was a positive correlation between the FIQ and EORTC-QoL-C30-symptom score (r = 0.726). CONCLUSION: We note that the frequency of FM in the operated breast cancer patients in this study was higher than that reported in normal populations in the literature. Also, we found that the presence of FM had negative effects on the quality of life of the breast cancer patients. Accordingly, in the evaluation of widespread pain and complaints of fatigue in long-surviving breast cancer patients, after metastatic disease is excluded, the probability of FM should be kept in mind, so that appropriate treatment can be initiated to improve their functional status and quality of life. PMID- 22322541 TI - "Atypical femoral fractures" during bisphosphonate exposure in adult hypophosphatasia. AB - We report a 55-year-old woman who suffered atypical subtrochanteric femoral fractures (ASFFs) after 4 years of exposure to alendronate and then zolendronate given for "osteoporosis." Before alendronate treatment, she had low bone mineral density. After several months of therapy, metatarsal stress fractures began. Bisphosphonate (BP) administration was stopped following the ASFFs, and the adult form of hypophosphatasia (HPP) was diagnosed from low serum alkaline phosphatase (ALP) activity, high endogenous levels of two natural substrates for the "tissue nonspecific" isoenzyme of ALP (TNSALP), and a heterozygous mutation within the gene that encodes this enzyme. Experience with other HPP families showed that her mutation (Arg71His) with a second defective TNSALP allele can cause severe HPP in infancy, and when heterozygous can cause mild HPP featuring premature loss of deciduous teeth in children. Because the skeletal disease of HPP results from extracellular accumulation of the TNSALP substrate inorganic pyrophosphate (PPi) and its inhibitory effect on mineralization, perhaps HPP patients or carriers will have adverse effects from BPs. BPs are analogues of PPi and can suppress bone turnover but also deactivate TNSALP. Our report is the first of BP exposure preceding ASFFs in adult HPP. To explore a potential role for TNSALP deactivation in ASFFs, mutation analysis of TNSALP should be studied in a cohort of these patients. Meanwhile, clinicians must suspect HPP when clinical or laboratory clues include premature loss of primary dentition, pseudofractures or recurrent poorly healing metatarsal stress fractures, a family history suggestive of HPP, or low serum ALP activity. If HPP is documented, BP treatment might be avoided. To establish the diagnosis of HPP, assays for two natural substrates for TNSALP and TNSALP mutation analysis are available in commercial laboratories. With positive findings, radiological or bone biopsy evidence of acquired osteomalacia would indicate the adult form of this inborn-error-of-metabolism. PMID- 22322542 TI - Thermal stability of embedded metal nanoparticles elongated by swift heavy ion irradiation: Zn nanoparticles in a molten state but preserving elongated shapes. AB - Solid Zn and V nanoparticles (NPs) embedded in silica were elongated by swift heavy ion (SHI) irradiation with 200 MeV Xe(14+) ions to a fluence of 5.0 * 10(13) ions cm(-2). Isochronal annealing was carried out in a vacuum from 200 to 1000 degrees C in steps of 100 degrees C for 10 min each. The degree of shape elongation was evaluated at room temperature (RT) by two different optical methods: linear dichroism spectroscopy and birefringence spectroscopy. In the as irradiated state, the samples showed an absorption band at 5 eV due to radiation induced defects in the silica in addition to the anisotropic absorption due to the elongated metal NPs. After annealing at 400 degrees C the defect band had completely disappeared, while the degree of shape elongation was almost unchanged or rather slightly increased in both the Zn and V NPs. The elongation of the Zn NPs slightly decreased but maintained a certain value after annealing at 500 degrees C, which is much higher than the melting point (MP) of Zn NPs (~420 degrees C). This observation indicates that shape elongation is mostly maintained even if the Zn NPs are in the molten state to some extent during annealing. The elongation of the Zn NPs was almost eliminated after annealing at 600 degrees C. In the case of the V NPs, elongation was maintained up to 800 degrees C but mostly eliminated at 900 degrees C. Since the recovery temperature of 900 degrees C from the elongated to the spherical shape is much lower than the MP of bulk V (1890 degrees C), we consider that the elongation is eliminated without melting of V NPs, i.e. via solid state mass transportation. The melting of NPs is not the key factor for the recovery to the spherical shape. PMID- 22322543 TI - Retinal arteriolar diameter and the prevalence and incidence of hypertension: a systematic review and meta-analysis of their association. AB - Hypertension is a leading risk factor for increased mortality and morbidity. One pathogenesis mechanism, increased peripheral vascular resistance, relates to arteriolar diameter. Retinal arterioles, visualized and measured through retinal images, provide an insight into the microvascular structure and hints of peripheral vascular resistance. Multiple studies have demonstrated an inverse association between increasing blood pressure and narrowing retinal arteriolar diameter. This systematic review summarizes the currently available evidence from cross-sectional and longitudinal population-based studies that have investigated this association. A meta-analysis of five cross-sectional studies (19,633 adults) provided an averaged regression coefficient of -3.07 MUm (95% CI, -3.73, -2.40) narrowing in retinal arteriolar diameter for every 10 mm Hg increase in mean arterial blood pressure. Four longitudinal studies (6,247 adults) with follow-up periods ranging from 3 to 7 years consistently showed that generalized retinal arteriolar narrowing (defined as the lowest tertile, quartile, or quintile in the population) was associated with an increased risk of incident hypertension (meta analysis odds ratio 1.91; 95% CI, 1.56-2.34). PMID- 22322544 TI - [Sonographic detection of microcalcifications - potential of new method]. AB - PURPOSE: Does the easier microcalcification detection (EMD) method enable sonographic visualization of microcalcifications in breast core biopsy specimens compared with mammography? MATERIALS AND METHODS: In a prospective randomized study, 105 core biopsy specimens obtained with stereotactic guidance were examined by mammography and ultrasound. EMD is integrated in a high-end ultrasound system and uses three level settings (0 - 2 blue, 3 - 5 violet, and 6 8 black-and-white; 14 MHz). Detection of microcalcifications per core specimen was determined for ultrasound and mammography. EMD image quality was rated on a scale of 1 - 9. ANOVA and Sidak post-hoc testing, Pearson regression analysis (r), and Spearman rank correlation (rho) were performed. The intraclass correlation coefficient (ICC) was calculated, and an ROC analysis was conducted. RESULTS: The blue color map 1 was assigned the highest mean score of 1.5 +/- 0.7 (p< 0.05 compared with black-and-white and violet). There was good correlation between the two modalities (r= 0.708 and rho= 0.694) with detection of 3.5 +/- 3.1 microcalcifications per specimen by ultrasound versus 4.3 +/- 4.8 by mammography (p> 0.05). The ICC of 0.773 indicates little disagreement between the two modalities. ROC analysis showed mammography to be superior to ultrasound compared with histological detection of microcalcifications (AUC= 0.837 vs. AUC= 0.728). CONCLUSION: Sonographic detection of microcalcifications in stereotactic biopsy specimens using the EMD method correlates well with digital mammography. Mammography is slightly superior. PMID- 22322545 TI - [The Tele-HF study]. PMID- 22322546 TI - [Viability and left ventricular dysfunction: what changes after STICH?]. PMID- 22322548 TI - [Clinical applications of MIBG SPECT in chronic heart failure]. AB - Heart failure is characterized by several abnormalities of sympathetic cardiac activity that can be assessed by 123I metaiodobenzylguanidine single photon emission computed tomography (MIBG SPECT). This technique may be useful in the clinical management of heart failure patients. Abnormal MIBG uptake has been demonstrated to be a predictor of death and arrhythmic events in heart failure patients with a prognostic power incremental to that of conventional risk markers; it may also be useful to identify patients at low risk of arrhythmias despite current guideline indications for an implantable cardioverter defibrillator (ICD) or patients at high risk for arrhythmias not fulfilling ICD indications. This review will focus on the clinical applications of MIBG SPECT in chronic heart failure, on the basis of the most recent evidence. PMID- 22322549 TI - [Imaging the innervation of the failing heart]. PMID- 22322550 TI - [Revascularization of the hibernated myocardium: a clinical problem still unsolved]. AB - The mid- and long-term outcome of revascularization procedures is still uncertain in patients with chronic left ventricular systolic dysfunction due to coronary artery disease. The identification of dysfunctional myocardial segments with residual viability that can improve after revascularization is pivotal for further patient management. Hibernating myocardium (chronically dysfunctional but still viable tissue) can be identified by positron emission tomography and cardiac magnetic resonance and its presence and extent can predict functional recovery after revascularization. Before beta-blockers were introduced as routine care for heart failure, surgical revascularization appeared to improve survival in these patients. Nowadays, novel medical treatments and devices such as cardiac resynchronization therapy and implantable cardioverter-defibrillators have improved prognosis of these patients and their use is supported by a number of clinical trials. A recently concluded randomized trial, the STICH (Surgical Treatment for Ischemic Heart Failure) trial, has assessed the prognostic benefit derived from revascularization added to optimal medical therapy in patients with ischemic left ventricular dysfunction. This is an overview of the pathophysiological mechanisms as well as the main clinical studies and meta analyses that have addressed this issue in the past four decades. Furthermore, a brief proposal for a randomized trial to assess effect on prognosis of revascularization of hibernating myocardium will be presented. PMID- 22322551 TI - [Defibrillator implantation associated with ventricular arrhythmia ablation: an emerging hybrid approach]. AB - Ventricular arrhythmias are an important cause of morbidity and mortality and are the leading cause of sudden cardiac death. Although implantable cardioverter defibrillators (ICD) proved to be effective in reducing both sudden cardiac death and all-cause mortality, the ideal therapy remains to be defined because ICD implantation allows to interrupt life-threatening ventricular arrhythmias but does not prevent them. ICD interventions, in terms of shock delivery and antitachycardia pacing, are often associated with invalidating symptoms, such as chest pain, sensation of rapid heartbeat and syncope, and may cause depression in many patients. Both appropriate and inappropriate shocks have been shown to be associated with a worse prognosis. Transcatheter ablation proved to be safe and effective in reducing arrhythmia relapse in patients who experience multiple ICD interventions or electrical storm. In the latter patient subset, ablation often represents the only possibility of interrupting such dramatic events. Ablation has also been evaluated in patients implanted with an ICD in secondary prevention, before device intervention. To date, transcatheter ablation represents an optimal opportunity, complementary to ICD, in the treatment of patients at high risk for sudden death and episodes of ventricular arrhythmias. PMID- 22322552 TI - [Association of carotid atherosclerosis with coronary artery disease: comparison between carotid ultrasonography and coronary angiography in patients with chest pain]. AB - BACKGROUND: Several studies have shown that the risk of cardiovascular events is higher in subjects with ultrasound evidence of subclinical carotid atherosclerosis. The aim of our study was to demonstrate the correlation between carotid atherosclerosis and severity of coronary artery disease in patients with typical chest pain who performed Doppler ultrasound of carotid arteries and diagnostic coronary angiography during hospitalization. METHODS: We studied 210 patients admitted to our cardiology unit for chest pain. Inclusion criteria were the presence of typical chest pain on admission to the emergency room and the performance of diagnostic coronary angiography and Doppler ultrasound examination of carotid arteries during hospitalization. Patients with positive biomarkers of myocardial infarction on admission to the emergency room and patients with a positive medical history for cardio- and cerebrovascular disease were excluded. RESULTS: Carotid ultrasound examination showed a 10% prevalence of normal carotid arteries, a 37% prevalence of intima-media carotid thickness and a 53% of asymptomatic carotid plaques. Coronary angiography showed that 29% of patients had normal coronary arteries, 26% had a coronary disease localized in a single vessel, 18% in two vessels, whereas 27% showed the involvement of three vessels. The presence of a normal carotid intima-media thickness was predominantly associated with the presence of angiographically normal coronary arteries (p=0.006), whereas the detection of asymptomatic carotid plaques at ultrasound examination was significantly correlated with three-vessel coronary artery disease (p=0.01). At logistic regression analysis, carotid atherosclerosis was predictive of severe coronary artery disease (odds ratio 2.1, 95% confidence interval 1.1-4.2, p=0.01). CONCLUSIONS: Given the significant correlation between the presence of preclinical carotid atherosclerosis and severity of coronary artery disease, the evaluation of carotid intima-media thickness might provide additional information for a more accurate determination of cardiovascular risk. PMID- 22322553 TI - [In-hospital management of acute coronary syndrome patients: influence of age, gender and admission department on medical policy and outcome]. AB - BACKGROUND: Although the improvement of therapeutic strategies is leading to a dramatic decline of in-hospital acute coronary syndrome (ACS) death rates, differences in care and prognosis of ACS patients exist when age, gender and admission department are considered. METHODS: The national hospital informative system was used. Only data recorded in three Italian Regions from December 1, 2005 to November 30, 2007 were analyzed. This approach allowed to identify 70 413 patients reporting ACS as primary or secondary diagnosis. The ACS cohort was stratified by age (<=64, 65-74 and >=75 years) and gender. ACS events were divided into two groups: 42 503 patients with non-ST-elevation ACS (NSTE-ACS) and 27 910 patients with ST-elevation ACS (STEMI). The proportion of NSTE-ACS and STEMI patients treated in general medicine or cardiology departments requiring a coronary procedure or extensive investigations, and in-hospital 30-day mortality rates adjusted by age and gender were analyzed. RESULTS: 19% of STEMI and 15% of NSTE-ACS patients are admitted to a general medicine department. For STEMI patients, the proportion increases up to 37.6% when females aged >=75 years are considered. Patients undergo a coronary procedure or extensive investigations less commonly in general medicine than in cardiology departments; in-hospital 30 day adjusted mortality rates in general medicine departments are approximately 2 fold higher than those recorded in cardiology departments (STEMI: 26.4 vs 16.7%; NSTE-ACS: 7.7 vs 4.2%). CONCLUSIONS: In-hospital mortality rates of ACS patients admitted to cardiology departments are lower than those reported in general medicine departments. Nevertheless, in-hospital management of women and elderly ACS patients does not completely comply with the recommended guidelines and exposes them to unfavorable prognosis. PMID- 22322554 TI - [Tako-tsubo syndrome during an attempt of pacemaker implantation in a patient with persistent left superior vena cava and absent right superior vena cava]. AB - Persistent left superior vena cava is a rare congenital abnormality. Cases of persistent left superior vena cava with an absent right superior vena cava or the presence of other congenital cardiovascular abnormalities have been rarely described. To the best of our knowledge, this is the first case of a patient with persistent left superior vena cava, absent right superior vena cava and tako tsubo syndrome observed during an attempt of pacemaker implantation. Such a condition was confirmed by means of contrast echocardiography and coronary angiography. PMID- 22322555 TI - [Double papillary fibroelastoma of the aortic valve in previous cerebral infarction]. PMID- 22322556 TI - [Training and accreditation in cardiovascular magnetic resonance imaging: a position paper of the Working Group on Magnetic Resonance Imaging of the Italian Society of Cardiology and of the Working Group on Cardiovascular Imaging of the Italian Association of Hospital Cardiologists]. AB - Cardiovascular magnetic resonance (CMR) imaging has become an established imaging modality requiring the definition of standards for data acquisition, reporting and training, recently addressed by a position statement of the Working Group on Cardiovascular Magnetic Resonance of the European Society of Cardiology (ESC). Taking into account the particular difficulties related to CMR implementation in our country, the Working Group on CMR of the Italian Society of Cardiology and the Working Group on Cardiovascular Imaging of the Italian Association of Hospital Cardiologists have prepared this document with the aim to address the logistic, cultural and training problems inhibiting CMR dissemination. The present paper provides recommendations for the inclusion in the School of Cardiology training curriculum of CMR training as suggested by the ESC training curriculum as well as recommendations concerning cardiovascular and radiological training for certification in CMR. The proposal for the institutional accreditation is discussed, including recommendations for case-load, case-mix, structured training programs, and safety of CMR studies. PMID- 22322557 TI - Reactivation of latent HIV-1 by a wide variety of butyric acid-producing bacteria. AB - Latently infected cells harbor human immunodeficiency virus type 1 (HIV-1) proviral DNA copies integrated in heterochromatin, allowing persistence of transcriptionally silent proviruses. It is widely accepted that hypoacetylation of histone proteins by histone deacetylases (HDACs) is involved in maintaining the HIV-1 latency by repressing viral transcription. HIV-1 replication can be induced from latently infected cells by environmental factors, such as inflammation and co-infection with other microbes. It is known that a bacterial metabolite butyric acid inhibits catalytic action of HDAC and induces transcription of silenced genes including HIV-1 provirus. There are a number of such bacteria in gut, vaginal, and oral cavities that produce butyric acid during their anaerobic glycolysis. Since these organs are known to be the major site of HIV-1 transmission and its replication, we explored a possibility that explosive viral replication in these organs could be ascribable to butyric acid produced from anaerobic resident bacteria. In this study, we demonstrate that the culture supernatant of various bacteria producing butyric acid could greatly reactivate the latently-infected HIV-1. These bacteria include Fusobacterium nucleatum (commonly present in oral cavity, and gut), Clostridium cochlearium, Eubacterium multiforme (gut), and Anaerococcus tetradius (vagina). We also clarified that butyric acid in these culture supernatants could induce histone acetylation and HIV-1 replication by inhibiting HDAC. Our observations indicate that butyric acid producing bacteria could be involved in AIDS progression by reactivating the latent HIV provirus and, subsequently, by eliminating such bacterial infection may contribute to the prevention of the AIDS development and transmission. PMID- 22322558 TI - Significant systemic therapeutic effects of high-LET immunoradiation by 212Pb trastuzumab against prostatic tumors of androgen-independent human prostate cancer in mice. AB - The purpose of this study was to determine therapeutic effects and systemic toxicity of 212Pb-trastuzumab in an orthotopic model of human prostate cancer cells in nude mice. TCMC-Trastuzumab was radiolabeled with 212Pb. The 212Pb trastuzumab generated from the procedure was intact and had high binding affinity with a dissociation constant (of 3.9+/-0.99 nM. PC-3MM2 cells, which expressed a lower level of HER2 both in culture and in tumors, were used in therapy studies. A single intravenous injection of 212Pb-trastuzumab reduced tumor growth by 60 80%, reduced aortic lymph node metastasis, and prolonged the survival of tumor bearing mice. Treatment with 212Pb-trastuzumab did not cause significant changes in body weight, serum glutamic pyruvic transaminase (SGPT), blood urea nitrogen (BUN), hematological profiles, and histological morphology of several major organs of tumor-bearing mice. These findings suggest that a systemic delivery of 212Pb-trastuzumab could be an effective modality for management of advanced human prostate cancer. PMID- 22322559 TI - Differential effects of paraoxonase 1 (PON1) polymorphisms on cancer risk: evidence from 25 published studies. AB - Paraoxonase is an HDL-associated enzyme that plays a preventive role against oxidative stress, which is thought to contribute to cancer development. PON1 activity varies widely among individuals, which is in part related to two common nonsynonymous polymorphisms in the PON1 gene (Q192R and L55M). The polymorphisms in PON1 have been implicated in cancer risk. However, results from the studies to date have been conflicting. To clarify the association, a meta-analysis was performed for 7,073 cases and 9,520 controls from 25 published case-control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Significant associations between PON1 L55M but not Q192R polymorphism and total cancer were observed from all the comparisons. In stratified analyses, PON1-55M allele was a risk factor for breast cancer. Similarly, increased risk was observed for prostate cancer (OR = 1.18, 95% CI: 1.01-1.36, P (heterogeneity) = 0.260) and Caucasian population (OR = 1.18, 95% CI: 1.02-1.38, P (heterogeneity) = 0.1) of the LM genotype, compared with the LL genotype. For PON1-Q192R polymorphism, PON1-192R allele was a decreased risk factor for cancer in the Asian group (RR vs QQ: OR = 0.61, 95% CI: 0.38-0.98, P (heterogeneity) = 0.268; QR vs QQ: OR = 0.71, 95% CI: 0.52-0.96, P (heterogeneity) = 0.130; RR + QR vs QQ: OR = 0.71, 95% CI: 0.53-0.95, P (heterogeneity) = 0.135). Although some modest bias could not be eliminated, this meta-analysis suggests that the PON1-55M allele is a risk factor for the development of cancer, in particular for breast cancer. Future studies with larger sample sizes are warranted to further evaluate these associations. PMID- 22322560 TI - Kinetic and thermodynamic study of cloned thermostable endo-1,4-beta-xylanase from Thermotoga petrophila in mesophilic host. AB - The 1,044 bp endo-1,4-beta-xylanase gene of a hyperthermophilic Eubacterium, "Thermotoga petrophila RKU 1" (T. petrophila) was amplified, from the genomic DNA of donor bacterium, cloned and expressed in mesophilic host E. coli strain BL21 Codon plus. The extracellular target protein was purified by heat treatment followed by anion and cation exchange column chromatography. The purified enzyme appeared as a single band, corresponding to molecular mass of 40 kDa, upon SDS PAGE. The pH and temperature profile showed that enzyme was maximally active at 6.0 and 95 degrees C, respectively against birchwood xylan as a substrate (2,600 U/mg). The enzyme also exhibited marked activity towards beech wood xylan (1,655 U/mg). However minor activity against CMC (61 U/mg) and beta-Glucan barley (21 U/mg) was observed. No activity against Avicel, Starch, Laminarin and Whatman filter paper 42 was observed. The K(m), V(max) and K (cat) of the recombinant enzyme were found to be 3.5 mg ml(-1), 2778 MUmol mg(-1)min(-1) and 2,137,346.15 s(-1), respectively against birchwood xylan as a substrate. The recombinant enzyme was found very stable and exhibited half life (t(1/2)) of 54.5 min even at temperature as high as 96 degrees C, with enthalpy of denaturation (DeltaH*(D)), free energy of denaturation (DeltaG*(D)) and entropy of denaturation (DeltaS*(D)) of 513.23 kJ mol(-1), 104.42 kJ mol(-1) and 1.10 kJ mol(-1)K(-1), respectively at 96 degrees C. Further the enthalpy (DeltaH*), Gibbs free energy (DeltaG*) and entropy (DeltaS*) for birchwood xylan hydrolysis by recombinant endo-1,4-beta xylanase were calculated at 95 degrees C as 62.45 kJ mol(-1), 46.18 kJ mol(-1) and 44.2 J mol(-1) K(-1), respectively. PMID- 22322561 TI - Functional polymorphism in the EpCAM gene is associated with occurrence and advanced disease status of cervical cancer in Chinese population. AB - The epithelial cell adhesion molecule (EpCAM) was originally identified as a tumor associated antigen, attributable to its high expression on rapidly proliferating tumors of epithelial origin. EpCAM plays vital roles in carcinogenesis, tumor progression and metastasis in most tumors. A non-synonymous polymorphism (rs1126497 C/T) was found in exon 3 of EpCAM, which cause a transition from 115 Met to 115 Thr. Another polymorphism (rs1421 A/G) in the 3'UTR causes loss of has-miR-1183 binding. We performed a multiple independent case-control analysis to assess the association between EpCAM genotypes and cervical cancer risk. Genotyping a total of 518 patients with cervical cancer and 723 control subjects in a Chinese population, we observed that the variant EpCAM genotypes (rs1126497 CT, and TT) were associated with substantially increased risk of cervical cancer. Compared with the rs1126497 CC genotype, CT genotype had a significantly increased risk of cervical cancer (Crude OR = 1.70; 95% CI = 1.33 2.20; adjusted OR = 1.72; 95% CI = 1.33-2.22), the TT carriers had a further increased risk of cervical cancer (Crude OR = 1.94; 95% CI = 1.01-3.72; adjusted OR = 1.96; 95%CI = 1.01-3.81), and there was a trend for an allele dose effect on risk of cervical cancer (P < 0.001). Moreover, the allele T increases the risk for invasive disease or metastatic disease, compared with C allele. However, there exists no significant difference in genotype frequencies of rs1421 A/G site between cases and controls (P = 0.798). These findings suggest that rs1126497 C/T polymorphism in EpCAM may be a genetic modifier for developing cervical cancer. PMID- 22322562 TI - Coronary artery abnormalities and sudden cardiac death. AB - Anomalous origin of a coronary artery (AOCA) can be associated with sudden cardiac death (SCD), particularly in young athletes. The diagnosis usually can be made by transthoracic echocardiography. In the case of patients for whom this method is not diagnostic, other methods are available including transesophageal echocardiography, cardiac magnetic resonance imaging (CMRI), and computed tomographic (CT) angiography. The decision to intervene is dependent on the type of lesion, the course of the coronary artery, its known association with SCD, and any symptoms present at the time of diagnosis. For patients without symptoms who have lesions less clearly associated with SCD [e.g., anomalous origin of the right coronary artery (AORCA)], the decision to intervene is more controversial. Further prospective studies hopefully will elucidate the optimum treatment pathway for such patients. PMID- 22322563 TI - Tetralogy of Fallot with infective endocarditis: an echocardiographic explanation of misleading clinical signs. AB - Echocardiography has a known key role in the diagnosis of infective endocarditis, the diagnosis of complications, follow-up evaluation after therapy, and prognostic assessment Habib (Eur J Echocardiogr 11:202-219, 3). This report describes a boy with tetralogy of Fallot who presented with infective endocarditis and large vegetation occluding the ventricular septal defect, thus resulting in a hemodynamically restrictive ventriculoseptal defect with misleading clinical signs. This case illustrates the role of echocardiography in both explaining clinical signs and providing hemodynamic data. PMID- 22322564 TI - Risk factors associated with morbidity and mortality after pulmonary valve replacement in adult patients with previously corrected tetralogy of Fallot. AB - Patients with palliated tetralogy of Fallot (TOF) often require pulmonary valve replacement in adulthood, yet the data regarding their outcomes are scarce. This study aimed to identify risk factors associated with postoperative complications in these patients and to establish long-term survival data for this patient group. A retrospective cohort study investigated 153 consecutive patients with a history of TOF repair who underwent pulmonary valve replacement at a single large academic center between March 1996 and March 2010. In part 1 of the study, logistic models were constructed to assess demographic, medical, and surgical risk factors for operative mortality; occurrence of a major adverse event (stroke, renal failure, prolonged ventilation, deep sternal infection, reoperation, or operative mortality); and prolonged hospital stay (>7 days). Risk factors with a p value less than 0.10 by univariate analysis were included in the subsequent multivariate analysis. In part 2 of the study, long-term, all-cause mortality was determined by construction of a Kaplan-Meier curve for the cohort. Seven patients died (4.5%). Significant risk factors for mortality in the multivariable analysis included age older than 40 years (odds ratio (OR) 9.89) and concomitant surgery (OR 6.65). A major adverse event occurred for 22 patients (14.4%). The only significant risk factor in the multivariable analysis for an adverse event was concomitant surgery (OR 6.42). The hospital stay was longer than 7 days for 31 patients (20.3%). The significant risk factors for a prolonged hospital stay included the presence of preoperative arrhythmias (OR 4.17), New York Heart Association class 3 (OR 4.35), and again, concomitant surgery (OR 4.2). Among the 146 hospital survivors, only 5 patients died in the intervening period. The predicted survival rates were 98.5% at 1 year, 96.7% at 5 years, and 93.5% at 10 years. Pulmonary valve replacement in adults with palliated TOF is a safe procedure with excellent long-term survival, but there remain important risk factors for postoperative mortality, prolonged hospital stay, and major adverse events. Awareness and modification of important risk factors may help to improve outcomes. PMID- 22322565 TI - Incomplete and atypical Kawasaki disease: a clinicopathologic paradox at high risk of sudden and unexpected infant death. AB - Incomplete Kawasaki disease (IKD) and atypical Kawasaki disease (AKD) represent rare conditions. Two cases of unexpected or sudden infant death are reported. The diagnosis for a 3-month-old girl was determined by echocardiography, and the child unexpectedly died despite appropriate treatment, whereas autopsy determined the diagnosis of AKD for a 4-month-old boy. In both patients, giant coronary artery aneurysms with thrombosis and vasculitis, myocarditis, and coagulative necrosis were shown at autopsy. These rare forms of IKD and AKD carry a poor prognosis and represent a paradox between the severe cardiovascular damage and the clinical presentation that mimics common and usually self-limiting exanthematic infectious disease in infancy. PMID- 22322566 TI - Myopericarditis in children: elevated troponin I level does not predict outcome. AB - Myopericarditis is primarily a pericarditic syndrome with some degree of myocardial involvement, as evident by elevated cardiac enzymes. Differentiating myopericarditis from acute coronary syndromes can be challenging and may require coronary angiography or perfusion studies. Data on myopericarditis and its outcome for children are scarce. This study delineates the demography, clinical presentation, and outcomes of myopericarditis for children and evaluates the prognostic value of elevated troponin I. The authors retrospectively reviewed 880 patients younger than 18 years of age who were admitted with diagnoses of chest pain, myocarditis, or pericarditis between 2000 and 2010 at their institution. Myopericarditis was defined as a clinical presentation of pericarditis in the presence of elevated levels of cardiac enzymes. Medical records were reviewed to abstract the demographic data, clinical presentation, evaluation, treatment, and follow-up outcomes. A total of 12 patients (1.4%) with myopericarditis were identified. All the patients were male, 8 (67%) of whom were Caucasian, and their median age was 16 years (range, 11-17 years). Two of the patients (17%) had recently used illicit drugs, and two (17%) had recently smoked cigarettes. At presentation, symptoms included chest pain in 12 patients (100%, 12/12), upper respiratory symptoms in 3 patients (25%, 3/12), and shortness of breath in 3 patients (25%, 3/12). No cardiac murmur or gallop was noted in any patient. Electrocardiographic (ECG) changes included diffuse ST-T changes (5 patients), localized ST-T changes (6 patients), and no ST-T changes (1 patient). All the patients had elevated levels of cardiac enzymes, with a median Troponin I level of 21.4 ng/ml (range, 5.0-134.4 ng/ml) and a median CK-MB level of 50.2 ng/ml (range, 7-135 ng/ml). Echocardiography showed normal left ventricular systolic function in all the patients (median ejection fraction, 61%; range, 56-69%). None had pericardial effusion during the first echocardiographic evaluation. Coronary angiography showed normal coronary arteries in all nine subjects for whom it was performed. Treatment of myopericarditis consisted of ibuprofen, acetaminophen, and/or aspirin. During a median follow-up period of 2 months (range, 2 weeks to 3 years), all the patients were asymptomatic with echocardiography showing normal left ventricular size and function. Myopericarditis was exclusively seen in male adolescents. Despite markedly elevated levels of cardiac enzymes, the clinical evolution of myopericarditis seems benign without any myocardial dysfunction. The inflammatory involvement of the myocardium appears to be self-limited without short-term, overt sequelae. An elevated troponin I level in myopericarditis, unlike acute coronary syndromes, does not seem to carry an adverse prognosis. Further studies are needed to evaluate the long-term prognosis for such patients. PMID- 22322567 TI - The Modified Glasgow Outcome Score for the prediction of outcome in patients after cardiac arrest: a prospective clinical proof of concept study. AB - The Glasgow-Pittsburgh cerebral performance categories (GP-CPC) and the Glasgow Outcome Score (GOS) have been used to categorize patients according to their neurological outcome for prognostic predictors in patients after cardiac arrest (CA). We postulated that inclusion of deaths without knowing the cerebral status into the group of patients with poor outcome after CA using the GP-CPC and GOS will lead to dilution of the prognostic power of the investigated biochemical marker. The present study was conducted to verify this issue by employing a modified outcome score, which we termed as Modified Glasgow Outcome Score (MGOS). In the present study, 97 patients were enrolled in a prospective manner. Serum NSE and S100B levels were measured daily for 7 days after admission to the intensive care unit. Neurological outcome was assessed by employing the GOS and MGOS after 6 months. By employing the GOS, 46 patients were categorized into the group of patients with poor outcome and 51 patients survived with good neurological outcome. Patients who died without certified brain damage or with unknown cerebral status after CA (n = 20) were separated from patients with poor outcome in the MGOS. The magnitude of NSE (S100B) elevation in patients with poor outcome categorized by the MGOS was approximately 1.7-fold (1.5) higher as compared with patients divided by the GOS. The mean calculated sensitivities and area under the curve values of NSE and S100B predicting poor outcome classified by the MGOS were significantly higher as compared with the GOS. Conclusively, inclusion of deaths without certified brain damage or with unknown cerebral status into the group of patients with poor outcome will lead to underestimation of the prognostic power of investigated biochemical markers such as NSE and S100B. The MGOS will help to avoid this bias. PMID- 22322569 TI - Drug-eluting stents versus bare metal stents in ST elevation myocardial infarction: from evidence to practice. AB - In 2001, drug-eluting stents (DES) were introduced as a strategy to decrease restenosis and need for re-intervention. As the utilization of DES grew in general practice, there was considerable use of DES in "off-label" patients not evaluated in the initial randomized clinical trials. Single-center and large registry studies were able to demonstrate that the clinical efficacy of DES persisted even in patient subgroups not included in the initial clinical trials. These observations provided support for evaluating DES in STEMI patients. We will consider the evidence that evaluates the relative safety and efficacy of DES compared to BMS in STEMI patients, as well as address practical issues faced in the routine clinical care of these patients. PMID- 22322568 TI - Longitudinal heterogeneity of coronary artery distensibility in plaques related to acute coronary syndrome. AB - BACKGROUND: How coronary distensibility contributes to stable or unstable clinical manifestations remains obscure. We postulated that the heterogeneous plaque distensibility is associated with unstable clinical presentations in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: Seventeen and 19 ACS-related and -unrelated lesions, respectively, were visualized using intravascular ultrasound imaging with simultaneous intracoronary pressure recording. Systolic and diastolic lumen cross-sectional areas were measured at the lesion site and at five evenly spaced sites between the proximal and distal reference sites. The coronary distensibility index and stiffness index beta were calculated for each site and averaged for each coronary segment. Maximal distensibility index, standard deviation and the difference between maximal and minimal distensibility indices within each segment were significantly higher in the ACS-related than -unrelated plaques (5.6 +/- 2.3 vs. 3.7 +/- 1.8, p < 0.001, 2.1 +/- 0.9 vs. 1.1 +/- 0.6, p < 0.001 and 5.3 +/- 2.3 vs. 2.8 +/- 1.5, p < 0.001, respectively). Moreover, the difference in the distensibility index between the lesion site of ACS-related plaques and the immediate proximal site was significantly larger (2.88 +/- 2.35 vs. 1.17 +/- 1.44, p = 0.022) than that in ACS-unrelated plaques. CONCLUSIONS: Coronary artery distensibility is longitudinally more heterogeneous in ACS-related than-unrelated plaques, especially between the lesion and the immediate proximal site. PMID- 22322570 TI - Ex vivo and preclinical assessment of an endothelial progenitor cell capturing bioengineered stent. AB - Although drug-eluting stents (DES) have significantly reduced the rates of restenosis as compared to bare metal stents, late stent thrombosis remains a major drawback, especially for "off-label" use. Delayed arterial healing, characterized by persistent fibrin deposition and poor endothelialization, has been shown to correlate with late DES thrombosis. To overcome these limitations, a "pro-healing" approach has been developed to capture circulating endothelial progenitor cells (EPC) to enhance endothelialization of the stent surface. EPC have the ability to migrate to sites of vascular injury and aid the regeneration of damaged and dysfunctional endothelium. Clinically, the safety of EPC-capture stent has been proven in numerous clinical trials with low incidence of late stent thrombosis. The focus of this review is to demonstrate the efficacy of the Genous stent in preclinical studies, specifically to show the effectiveness of the anti-CD34+ coating in promoting endothelialization and reducing thrombogenicity. PMID- 22322571 TI - Advantages of novel BioMimeTM Sirolimus Eluting Coronary Stent system. Moving towards biomimicry. AB - Since the first reported use of percutaneous transluminal coronary angioplasty (PTCA), advancements in interventional cardiology arena have been fast paced. Within the last ten years, these developments have been exponential. Developers & clinicians are fast adapting from the learning curve awarded by the time course of DES evolution. In that light BioMimeTM Sirolimus Eluting Coronary Stent comes as a fresh thought in taking stents towards a biomimicry concept. The stent is built on an ultra-low strut thickness (65 um) cobalt chromium stent platform, using an intelligent hybrid of close and open cells allowing for morphology mediated expansion, employs a well known anti-proliferative - Sirolimus that elutes from a biodegradable co-polymer formulation in 30 days and ensures high coating integrity and low coating thickness of 2 um. The resultant stent demonstrates almost 100% endothelialization at 30 days in preclinical model and zero percent MACE >18 months in the primary efficacy and safety clinical study. PMID- 22322572 TI - Advantages of MGuard coronary stent system. AB - Effectiveness of percutaneous coronary intervention (PCI) within thrombus containing lesions (ST-segment elevation myocardial infarction setting, degenerated saphenous venous grafts) is limited by the risk of occurrence of distal embolization and no-reflow phenomenon. Several pharmacological agents, as well as mechanical devices (i.e. manual aspiration catheters/mechanical thrombectomy, proximal and distal protection devices) were introduced, in the last years, to reduce the risk of angiographic complications during percutaneous coronary intervention and to improve myocardial reperfusion. Recently, the MGuard stent (Inspire MD, Tel Aviv, Israel), a bare-metal stent covered by micron level mesh, which allows to prevent distal embolization by blocking the atherothrombi prolapse through the stent struts during deployment has been introduced. This article discusses the data concerning safety and efficacy of mesh covered stent implantation in a ST-segment elevation myocardial infarction setting, as well as during percutaneous coronary intervention in saphenous venous grafts. PMID- 22322573 TI - New DES: a new step forward? AB - Despite the benefits of first generation drug eluting stents (DES), concerns have been raised over their long term safety in particular the risk of stent thrombosis. As a result, the current generation and novel DES have been developed, the latter includes DES with biocompatible and biodegradable polymers, polymer free DES and completely bioresorbable stent platforms. Many of these stents are currently under evaluation in clinical trials, and early results are promising. This paper reviews the progress thus far in DES technology and aims to highlight the impact of recent DES innovations on clinical efficacy and safety. PMID- 22322574 TI - Update on percutaneous mitral valve therapy: clinical results and real life experience. AB - Mitral regurgitation (MR) is a common valvulopathy worldwide increasing in prevalence. Cardiac surgical intervention, preferable repair, is the standard of care, but a relevant number of patients with severe MR do not undergo surgery because of high peri-operative risk. Percutaneous mitral valve repair with the MitraClip System has evolved as a new tool for the treatment of severe MR. The procedure simulates the surgical edge-to-edge technique, developed by Alfieri in 1991, creating a double orifice valve by a permanent approximation of the two mitral valve leaflets. Several preclinical studies, registries and Food and Drug Administration approved clinical trials (EVEREST, ACCESS-EU) are currently available. The percutaneous approach has been recently studied in a randomized controlled trial, concluding that the device is less effective at reducing MR, when compared with surgery, by associated with a lower adverse event rate. The patients enrolled in this trial had a normal surgical risk and mainly degenerative MR with preserved left ventricular function. On the other hand, results derived from the clinical "real life" experience, show that patients actually treated in Europe present a higher surgical risk profile, more complex mitral valve anatomy and functional MR in the most of cases. Thus these data suggest that MitraClip procedure is feasible and safe in this subgroup of patients that should be excluded from the EVEREST trial due to rigid exclusion criteria. Despite the promising results clinical experience is still small, and no data related the durability are currently available. Therefore, MitraClip device should be reserved now to high risk or inoperable patients. PMID- 22322575 TI - My rules of a perfect SAPIENTM transcatheter aortic valve implantation. AB - Transcatheter aortic valve implantation has been established as an alternative treatment option for those patients with aortic stenosis (AO), who are high risk or unsuitable for surgical aortic valve replacement. Since its introduction, transcatheter aortic valve implantation has been mainly performed either by a percutaneous approach through the femoral arteries or by using a transapical approach via a left-sided mini-thoracotomy. More recently, experience on alternative access routes such as the subclavian artery and the ascending aorta has been reported in a small number of patients. The Edwards SAPIENTM transcatheter heart valve (Edwards Lifesciences, Irvine, CA, USA) was the first balloon-expandable transcatheter heart valve to receive CE-Mark certification in Europe for transfemoral and transapical aortic valve implantation in 2007/2008. However, it also has been used for transcatheter procedures using access through ascending aorta and subclavian artery. Appropriate patient selection is key for a successful transcatheter aortic valve program and should be in the responsibility of the heart team of interventional cardiologists, cardiac surgeons, cardiac imaging specialists, anesthetists and geriatrists. Their mixture of skills will enable the team to build patient care pathways in which patients are assessed regarding cardiac and non-cardiac comorbidities, the most appropriate type of treatment is jointly agreed, and finally various treatment options are delivered. In this review we highlight the cornerstones of a successful transcatheter aortic valve program using the Edwards SAPIENTM valve. We focus in particular on preoperative diagnostics, patient selection and potential strengths and weaknesses of the various access routes to offer a guideline for future experience. PMID- 22322576 TI - Review of the MitraClip clinical evidence. AB - MitraClip system is the only catheter-based device for percutaneous mitral valve repair available for clinical use, after receipt of the CE Mark in 2008, while it is currently under review for FDA approval in the US. To date, over 3500 MitraClip implants have been performed worldwide, mainly in high risk surgical patients. The aim of this review is to review all the current evidences of the MitraClip therapy in an aim to define its clinical role in the treatment of mitral regurgitation (MR). PMID- 22322577 TI - Glycoprotein IIb/IIIa inhibitors and bivalirudin in patients undergoing percutaneous coronary intervention. AB - Percutaneous coronary intervention (PCI) is currently the standard of care for patients presenting with acute coronary syndrome (ACS), as well those patients with "stable" angina who have failed medical therapy in whom PCI is an acceptable alternative to surgical revascularization. The aim of adjunctive antiplatelet and antithrombotic therapy during PCI is to alleviate the risks associated with platelet activation and aggregation, iatrogenic plaque rupture, and thrombus formation during. The aim of this review is to summarize the evidence that has emerged from the randomized studies comparing a strategy combining heparin and a glycoprotein IIb/IIIa inhibitor (GPI) with that of bivalirudin in patients undergoing elective and urgent PCI. PMID- 22322578 TI - New therapies for cardiogenic shock. AB - Cardiogenic shock is a serious complication of acute myocardial infarction and occurs as a consequence of acute left ventricular failure and subsequent inappropriate tissue perfusion. While its incidence has been reported to be as high as 10% in the late 90ties, it has been steadily declining to currently less than 6% since the implementation of early revascularization as a class I indication in current guidelines. Despite recent advances in the treatment of cardiogenic shock, mortality is still high at approximately 50%. Current therapeutic approaches include early revascularization, fluid resuscitation, inotropic and vasopressor therapy, and mechanical circulatory support using intra aortic balloon counterpulsation or percutaneous left ventricular assist devices. Novel treatment options such as specific inhibitors of inducible nitric oxide synthase or newer developments in mechanical circulatory support might be beneficial and should be tested in adequately powered randomized trials. However, difficulties in enrolling cardiogenic shock patients in randomized controlled trials are considerable. Until more data are available, cardiogenic shock patients should be treated aggressively with early revascularization and mechanical circulatory support to increase their probability of survival. PMID- 22322579 TI - Indications, techniques and results of percutaneous patent foramen ovale closure. AB - Patent foramen ovale (PFO) has been shown to be more prevalent in certain disease states, suggesting a potentially causative role in some patients with cryptogenic stroke, migraine headache or a number of other conditions. Percutaneous PFO closure has become a reasonable treatment option in a subset of those patients. Our objective is to review the possible indications of PFO closure. We further elucidate the technical aspects of PFO closure, provide an overview of the available devices and summarize results of PFO closure procedures. PMID- 22322581 TI - Patterns of autobiographical memory in adults with autism spectrum disorder. AB - Two studies are presented that explored the effects of experimental manipulations on the quality and accessibility of autobiographical memories in adults with autism spectrum disorder (ASD), relative to a typical comparison group matched for age, gender and IQ. Both studies found that the adults with ASD generated fewer specific memories than the comparison group, and took significantly longer to do so. Despite this, experimental manipulations affected two indices of autobiographical memory (specificity and retrieval latency) similarly in both groups. These results suggest that adults with ASD experience a quantitative reduction in the speed and specificity of autobiographical memory retrieval, but that when they do retrieve these memories, they do so in a way that is qualitatively similar to that of typical adults. PMID- 22322582 TI - Brief report: stereotypes in autism revisited. AB - Autism involves core impairments in social cognition. Given that social learning underlies the acquisition of stereotypes, it was hypothesized that use of stereotypes would be reduced in autism. Contrary to this prediction, previous studies found the same use of stereotypes in autistic individuals as in controls. Measurement of stereotypes, however, can be biased by effects of social desirability, which previous studies did not account for. In the current study we therefore employed an implicit approach, using the Implicit Association Test (IAT), which assesses more automatic components of stereotypes, in nineteen individuals with autism and nineteen controls. The data suggest that while both groups do show the use of stereotypes to some extent, autistic individuals have less stereotypical attitudes against the investigated minority. PMID- 22322583 TI - Mechanical properties and in vitro behavior of nanofiber-hydrogel composites for tissue engineering applications. AB - Hydrogel-based biomaterial systems have great potential for tissue reconstruction by serving as temporary scaffolds and cell delivery vehicles for tissue engineering (TE). Hydrogels have poor mechanical properties and their rapid degradation limits the development and application of hydrogels in TE. In this study, nanofiber reinforced composite hydrogels were fabricated by incorporating electrospun poly(epsilon-caprolactone) (PCL)/gelatin 'blend' or 'coaxial' nanofibers into gelatin hydrogels. The morphological, mechanical, swelling and biodegradation properties of the nanocomposite hydrogels were evaluated and the results indicated that the moduli and compressive strengths of the nanofiber reinforced hydrogels were remarkably higher than those of pure gelatin hydrogels. By increasing the amount of incorporated nanofibers into the hydrogel, the Young's modulus of the composite hydrogels increased from 3.29 +/- 1.02 kPa to 20.30 +/- 1.79 kPa, while the strain at break decreased from 66.0 +/- 1.1% to 52.0 +/- 3.0%. Compared to composite hydrogels with coaxial nanofibers, those with blend nanofibers showed higher compressive strength and strain at break, but with lower modulus and energy dissipation properties. Biocompatibility evaluations of the nanofiber reinforced hydrogels were carried out using bone marrow mesenchymal stem cells (BM-MSCs) by cell proliferation assay and immunostaining analysis. The nanocomposite hydrogel with 25 mg ml(-1) PCL/gelatin 'blend' nanofibers (PGB25) was found to enhance cell proliferation, indicating that the 'nanocomposite hydrogels' might provide the necessary mechanical support and could be promising cell delivery systems for tissue regeneration. PMID- 22322584 TI - Antithrombotic therapy in heart failure. AB - Patients with congestive heart failure have a significant risk of stroke due to thromboembolism from the dilated left ventricle. Two relatively small trials suggest that oral anticoagulation with vitamin-K antagonists may reduce this risk when compared with placebo, aspirin or clopidogrel. However, more studies are eagerly awaited. So far, physicians seeing patients with heart failure should decide who needs antithrombotic prophylaxis on a case-by-case basis, especially since most heart failure patients have significant comorbidity precluding the use of oral anticoagulant. PMID- 22322585 TI - Traumatic aortic arch aneurysm in a left-handed deer hunter. PMID- 22322586 TI - The linear response kernel of conceptual DFT as a measure of aromaticity. AB - We continue a series of papers in which the chemical importance of the linear response kernel chi(r,r') of conceptual DFT is investigated. In previous contributions (J. Chem. Theory Comput. 2010, 6, 3671; J. Phys. Chem. Lett. 2010, 1, 1228; Chem. Phys. Lett. 2010, 498, 192), two computational methodologies were presented and it was observed that the linear response kernel could serve as a measure of electron delocalisation, discerning inductive, resonance and hyperconjugation effects. This study takes the analysis one step further, linking the linear response kernel to the concept of aromaticity. Based on a detailed analysis of a series of organic and inorganic (poly)cyclic molecules, we show that the atom-condensed linear response kernel discriminates between aromatic and non-aromatic systems. Moreover, a new quantitative measure of aromaticity, termed the para linear response (PLR) index, is introduced. Its definition was inspired by the recent work published around the para delocalisation index (PDI). Both indices are shown to correlate very well, which emphasises the linear response kernel's value in the theoretical description of aromaticity. PMID- 22322587 TI - From hexaoxy-[6]pericyclynes to carbo-cyclohexadienes, carbo-benzenes, and dihydro-carbo-benzenes: synthesis, structure, and chromophoric and redox properties. AB - When targeting the quadrupolar p-dianisyltetraphenyl-carbo-benzene by reductive treatment of a hexaoxy-[6]pericyclyne precursor 3 with SnCl(2)/HCl, a strict control of the conditions allowed for the isolation of three C(18)-macrocyclic products: the targeted aromatic carbo-benzene 1, a sub-reduced non-aromatic carbo cyclohexadiene 4A, and an over-reduced aromatic dihydro-carbo-benzene 5A. Each of them was fully characterized by its absorption and NMR spectra, which were interpreted by comparison with calculated spectra from static structures optimized at the DFT level. According to the nucleus-independent chemical shift (NICS) value (NICS~-13 ppm), the macrocyclic aromaticity of 5A is indicated to be equivalent to that of 1. This is confirmed by the strong NMR spectroscopic deshielding of the ortho-CH protons of the aryl substituents, but also by the strong shielding of the internal proton of the endocyclic trans-CH=CH double bond that results from the hydrogenation of one of the C=C bonds of 3. Both the aromatics 1 and 5A exhibit a high crystallinity, revealed by SEM and TEM images, which allowed for a structural determination by using an X-ray microsource. A good agreement with calculated molecular structures was found, and columnar assemblies of the C(18) macrocycles were evidenced in the crystal packing. The non-aromatic carbo-cyclohexadiene 4A is shown to be an intermediate in the formation of 1 from 3. It exhibits a remarkable dichromism in solution, which is related to the occurrence of two intense bands in the visible region of its UV/Vis spectrum. These properties could be attributed to the dibutatrienylacetylene (DBA) unit that occurs in the three chromophores, but which is not involved in a macrocyclic pi-delocalization in 4A only. A versatile redox behavior of the carbo-chromophores is evidenced by cyclic voltammetry and was analyzed by calculation of the ionization potential, electron affinity, and frontier molecular orbitals. PMID- 22322588 TI - Synovial xanthomatosis: are there clues to mechanisms for this rare disease? AB - We report a 64-year-old man with arthritis and nodules to describe that this picture can be caused by normo-lipidemic xanthomas. Light and electron microscopy (EM) plus polymerase chain reaction (PCR) studies were performed for diagnosis and investigation. These showed features typical of xanthomas plus PCR and EM evidence of possible infection with Chlamydia pneumoniae as a pathogenetic mechanism deserving consideration. With such rare diseases, any clues to possible mechanisms seem important to record and thus to encourage future investigations. This uncommon cause of arthritis and nodules had been confused with rheumatoid arthritis by others in this case. PMID- 22322589 TI - Safety and response to influenza vaccine in patients with systemic-onset juvenile idiopathic arthritis receiving tocilizumab. AB - OBJECTIVE: We investigated the safety and efficacy of administering influenza vaccines to patients with systemic-onset juvenile idiopathic arthritis (sJIA) treated with tocilizumab. PATIENTS AND METHODS: The subjects were 27 sJIA patients treated with tocilizumab and 17 healthy age- and sex-matched volunteers. Serum samples were collected prior to and 4-7 weeks after vaccination. Hemagglutination inhibition values of the vaccine were taken as the antibody titers. The duration of tocilizumab administration and the daily doses of prednisolone per unit body weight were analyzed to identify factors affecting the responses of the sJIA patients to influenza vaccination. We questioned all the subjects about whether they had contracted influenza and whether they had had adverse reactions to the influenza vaccination. We compared steroid doses in sJIA patients before and after vaccination to document any worsening of the underlying disease. RESULTS: The efficacy of influenza vaccination did not differ significantly between the sJIA group and the healthy controls. The duration of tocilizumab administration did not affect the response of the sJIA patients to the influenza vaccination. None of the sJIA patients experienced either severe adverse reactions or disease exacerbation after the influenza vaccination. CONCLUSION: We found that sJIA patients treated with tocilizumab could be effectively and safely immunized with the influenza vaccine. PMID- 22322590 TI - Acid ceramidase-mediated production of sphingosine 1-phosphate promotes prostate cancer invasion through upregulation of cathepsin B. AB - Invasiveness is one of the key features of aggressive prostate cancer; however, our understanding of the precise mechanisms effecting invasion remains limited. The ceramide hydrolyzing enzyme acid ceramidase (AC), overexpressed in most prostate tumors, causes an aggressive and invasive phenotype through downstream effectors that have not yet been well characterized. Here, we demonstrate that AC, through generation of sphingosine-1-phosphate (S1P), promotes Ets1 nuclear expression and binding to the promoter region of matrix-degrading protease cathepsin B. Through confocal microscopy and flow cytometry, we found that AC overexpression promotes pericellular localization of cathepsin B and its translocation to the outer leaflet of the cell membrane. AC overexpressing cells have an increased abundance of cathepsin B-enriched invasive structures and enhanced ability to invade through a collagen matrix, but not in the presence of an inhibitor of cathepsin B. In human prostate tissues, AC and cathepsin B overexpression were strongly associated and may relate to poor outcome. These results demonstrate a novel pathway by which AC, through S1P, promotes an invasive phenotype in prostate cancer by causing overexpression and secretion of cathepsin B through activation and nuclear expression of Ets1. As prostate cancer prognosis is dramatically worse when invasion has occurred, this study provides critical insight into the progression toward lethal prostate cancer. PMID- 22322591 TI - Early changes of a novel APC-dependent thrombin generation assay during chemotherapy independently predict venous thromboembolism in cancer patients--a pilot study. AB - PURPOSE: Identifying cancer patients who are most at risk for venous thromboembolism (VTE) is essential to improve timely delivery of chemotherapy. Several studies have been performed to identify novel candidate biomarkers, but no agreement has yet been reached. In this light, we sought to analyze whether a dynamic evaluation of early changes of activated protein C (APC) function during chemotherapy could be predictive of a first VTE episode in cancer outpatients, thus improving risk stratification. METHODS: A retrospective single-center pilot study was conducted to investigate the adequacy of a dynamic evaluation of a novel APC-dependent thrombin generation assay (HemosIL ThromboPath (ThP)) in predicting VTE in 208 ambulatory cancer patients, enrolled on the basis of tight inclusion criteria, prior to start and before the second cycle of a new chemotherapy regimen. RESULTS: Retrospective analysis of samples showed the occurrence of an acquired APC resistance during chemotherapy, which was predictive of VTE. Univariate Cox proportional hazards survival analysis showed that early ThP changes predicted VTE (stable vs. decreasing ThP: hazard ratio (HR) 0.21; 95% CI 0.10-0.19; p < 0.0001), which was confirmed in the multivariate model (HR 0.25; CI 0.12-0.52, p < 0.0001). Stratification of patients according to a risk assessment model showed a 0.18 HR for stable vs. decreasing ThP assay results in an intermediate risk group. CONCLUSIONS: We may thus conclude that early changes of ThP assay in patients on active chemotherapy enhance VTE risk stratification, helping in identifying a population of cancer patients who might benefit from thromboprophylaxis. PMID- 22322592 TI - Palliative care in poor-performance status small cell lung cancer patients: is there a mandatory role for chemotherapy? AB - PURPOSE: Small cell lung cancer (SCLC) is an aggressive malignancy but with a high response rate to chemotherapy. Eastern Cooperative Oncology Group performance status (ECOG PS) has been recognized as one of the main prognostic factors in SCLC. There are few data about risk-benefit ratio of chemotherapy over exclusive best supportive care in ECOG PS 3 and 4 patients. This study was performed to assess the outcome of poor ECOG PS SCLC patients that received chemotherapy in our institution. METHODS: A retrospective review of medical records from patients with ECOG PS 3-4 SCLC, who received systemic chemotherapy, was performed between January 2001 and December 2006 at the Instituto Nacional do Cancer, Rio de Janeiro, Brazil. RESULTS: A total of 40 patients were included. Extensive disease was observed in 85% of patients and 25% had PS 4. The median overall survival was 53 days (64 days for ECOG PS 3 and 7 days for ECOG PS 4). There were 30% of early deaths. On univariate analysis, lactate dehydrogenase value, need for hospital admission, and exposure to radiotherapy had impact on survival. ECOG PS 3 patients had better survival than PS 4 patients, even when adjusted for stage. On multivariate analysis, ECOG PS, combined with stage, sustained a major influence on survival. CONCLUSIONS: Median survival for ECOG PS 4 patients treated with chemotherapy in our series was extremely short with a high rate of early deaths. ECOG PS 3 patients also showed a poor survival. These data suggest that we need a more comprehensive approach and further studies, regarding the palliative care of this high-risk population. PMID- 22322593 TI - Physicians' self-assessment of cancer pain treatment skills--more training required. AB - PURPOSE: Adequate pain control is essential in cancer treatment. We surveyed Finnish physicians' perception on their skills and training needs on palliative pain management. METHODS: A structured questionnaire with multiple choices and open ended questions was used for collecting data in 2006-2008. Of 720 physicians participating, 59 were working in oncology and 661 physicians in internal medicine, geriatrics, and primary health care. RESULTS: The principles of the WHO guidelines of cancer pain management were not well known. Forty-six percent of oncologists and 32% of other physicians (P < 0.0001) knew the analgesic ladder consisting of three steps. Forty-seven percent of oncologists and 61% of other physicians considered pain treatment of cancer patients being well managed in Finland. Only 24% of oncologists and 5% of other physicians considered the education in palliative care being currently at a satisfactory level. Oncologists reported a need of training in interaction and communication skills, ethical questions, and palliative home care. The other physicians expressed the strongest need for training in pain management and palliative care. CONCLUSIONS: To have more confidence in treating cancer, pain physicians would benefit in training and education in palliative care. It should be systematically included both in general and specialist training and continuous medical education. PMID- 22322594 TI - Interaction of acetonitrile with trifluoromethanesulfonic acid: unexpected formation of a wide variety of structures. AB - Interaction of acetonitrile with trifluoromethanesulfonic acid has been studied by multinuclear NMR and ESI-MS. It has been found that the interaction results in formation of a great variety of different cations and neutral compounds which is controlled by the ratio of CH(3)CN to TfOH. In the presence of an excess of the acid (molar ratio 1 : 8-14) diprotonated N-acetylacetamidine 1 is formed as the major product, which eventually transforms into protonated acetamidine 3 and acetic acid 4. At molar ratio of (1 : 1-2) diprotonated 2,4-dimethyl-6 methylidene-3H-1,3,5-triazine 12, tautomer of the diprotonated trimethyl-s triazine 11, becomes the main product at an early stage of the reaction and diprotonated 1-(dimethyl-1,3,5-triazin-2-yl)prop-1-en-2-ol 15 at a later stage. In the case of a large excess of acetonitrile (4-20 : 1) trication 17 is formed as a result of the interaction between 11 and 12 along with some oligomers [(CH(3)CN)(3)](n) (n = 4-12). PMID- 22322595 TI - Endothelin-converting enzyme-1 actions determine differential trafficking and signaling of corticotropin-releasing factor receptor 1 at high agonist concentrations. AB - CRF receptor 1 (CRF(1)), a key neuroendocrine mediator of the stress response, has two known agonists corticotropin-releasing factor (CRF) and urocortin 1 (Ucn1). Here we report that endothelin-converting enzyme-1 (ECE-1) differentially degrades CRF and Ucn1; ECE-1 cleaves Ucn1, but not CRF, at critical residue Arginine-34/35', which is essential for ligand-receptor binding. At near K(D) agonist concentration (30 nm), both Ucn1- and CRF-mediated Ca(2+) mobilization are ECE-1 dependent. Interestingly, at high agonist concentration (100 nm), Ucn1 mediated Ca(2+) mobilization remains ECE-1 dependent, whereas CRF-mediated mobilization becomes independent of ECE-1 activity. At high agonist concentration, ECE-1 inhibition disrupted Ucn1-, but not CRF-induced CRF(1) recycling and resensitization, but did not prolong the association of CRF(1) with beta-arrestins. RNA interference-mediated knockdown of Rab suggests that both Ucn1- and CRF-induced CRF(1) resensitization is dependent on activity of Rab11, but not of Rab4. CRF(1) behaves like a class A G protein-coupled receptor with respect to transient beta-arrestins interaction. We propose that differential degradation by ECE-1 is a novel mechanism by which CRF(1) receptor is protected from overactivation by physiologically relevant high concentrations of higher affinity ligand to mediate distinct resensitization and downstream signaling. PMID- 22322596 TI - Research resource: the pdx1 cistrome of pancreatic islets. AB - The homeodomain transcription factor pancreas duodenal homeobox 1 (Pdx1, also known as insulin promoter factor 1) is a master regulator of pancreas development, as mice or humans lacking Pdx1 function are a pancreatic. Importantly, heterozygous mutations in Pdx1 cause early and late onset forms of diabetes in humans. Despite these central roles in development and adult beta cell function, we have only rudimentary knowledge of the transcriptome targets of Pdx1 that mediate these phenotypes. Therefore, we performed global location analysis of Pdx1 occupancy in pancreatic islets. We used evolutionary conservation of target genes to identify the most relevant Pdx1 targets by performing chromatin immunoprecipitation sequencing on both human and mouse islets. Remarkably, the conserved target set is highly enriched for genes annotated to function in endocrine system and metabolic disorders, various signaling pathways, and cell survival, providing a molecular explanation for many of the phenotypes resulting from Pdx1 deficiency. PMID- 22322597 TI - Cryptorchidism in mice with an androgen receptor ablation in gubernaculum testis. AB - Androgens play a critical role in the development of the male reproductive system, including the positioning of the gonads. It is not clear, however, which developmental processes are influenced by androgens and what are the target tissues and cells mediating androgen signaling during testicular descent. Using a Cre-loxP approach, we have produced male mice (GU-ARKO) with conditional inactivation of the androgen receptor (Ar) gene in the gubernacular ligament connecting the epididymis to the caudal abdominal wall. The GU-ARKO males had normal testosterone levels but developed cryptorchidism with the testes located in a suprascrotal position. Although initially subfertile, the GU-ARKO males became sterile with age. We have shown that during development, the mutant gubernaculum failed to undergo eversion, a process giving rise to the processus vaginalis, a peritoneal outpouching inside the scrotum. As a result, the cremasteric sac did not form properly, and the testes remained in the low abdominal position. Abnormal development of the cremaster muscles in the GU-ARKO males suggested the participation of androgens in myogenic differentiation; however, males with conditional AR inactivation in the striated or smooth muscle cells had a normal testicular descent. Gene expression analysis showed that AR deficiency in GU-ARKO males led to the misexpression of genes involved in muscle differentiation, cell signaling, and extracellular space remodeling. We therefore conclude that AR signaling in gubernacular cells is required for gubernaculum eversion and outgrowth. The GU-ARKO mice provide a valuable model of isolated cryptorchidism, one of the most common birth defects in newborn boys. PMID- 22322598 TI - DNA demethylation-dependent AR recruitment and GATA factors drive Rhox5 homeobox gene transcription in the epididymis. AB - Mammalian male fertility depends on the epididymis, a highly segmented organ that promotes sperm maturation and protects sperm from oxidative damage. Remarkably little is known about how gene expression is controlled in the epididymis. A candidate to regulate genes crucial for epididymal function is reproductive homeobox gene on X chromosome (RHOX)5, a homeobox transcription factor essential for optimal sperm motility that is expressed in the caput region of the epididymis. Here, we report the identification of factors that control Rhox5 gene expression in epididymal cells in a developmentally regulated and region-specific fashion. First, we identify GATA transcription factor-binding sites in the Rhox5 proximal promoter (Pp) necessary for Rhox5 expression in epididymal cells in vitro and in vivo. Adjacent to the GATA sites are androgen-response elements, which bind to the nuclear hormone receptor androgen receptor (AR), and are responsible for the AR-dependent expression of Rhox5 in epididymal cells. We provide evidence that AR is recruited to the Pp in a region-specific and developmentally regulated manner in the epididymis that is dictated not only by differential AR availability but differential methylation of the Pp. Site specific methylation of the Pp cytosine and guanine separated by one phosphate, most of which overlap with androgen-response elements, inhibited both AR occupancy at the Pp and Pp-dependent transcription in caput epididymal cells. Together, our data support a model in which DNA methylation, AR, and GATA factors collaborate to dictate the unique developmental and region-specific expression pattern of the RHOX5 homeobox transcription factor in the caput epididymis, which in turn controls the expression of genes critical for promoting sperm motility and function. PMID- 22322599 TI - The role of the vitamin D receptor and ERp57 in photoprotection by 1alpha,25 dihydroxyvitamin D3. AB - UV radiation (UVR) is essential for formation of vitamin D(3), which can be hydroxylated locally in the skin to 1alpha,25-dihydroxyvitamin D(3) [1,25 (OH)(2)D(3)]. Recent studies implicate 1,25-(OH)(2)D(3) in reduction of UVR induced DNA damage, particularly thymine dimers. There is evidence that photoprotection occurs through the steroid nongenomic pathway for 1,25 (OH)(2)D(3) action. In the current study, we tested the involvement of the classical vitamin D receptor (VDR) and the endoplasmic reticulum stress protein 57 (ERp57), in the mechanisms of photoprotection. The protective effects of 1,25 (OH)(2)D(3) against thymine dimers were abolished in fibroblasts from patients with hereditary vitamin D-resistant rickets that expressed no VDR protein, indicating that the VDR is essential for photoprotection. Photoprotection remained in hereditary vitamin D-resistant rickets fibroblasts expressing a VDR with a defective DNA-binding domain or a mutation in helix H1 of the classical ligand-binding domain, both defects resulting in a failure to mediate genomic responses, implicating nongenomic responses for photoprotection. Ab099, a neutralizing antibody to ERp57, and ERp57 small interfering RNA completely blocked protection against thymine dimers in normal fibroblasts. Co-IP studies showed that the VDR and ERp57 interact in nonnuclear extracts of fibroblasts. 1,25-(OH)(2)D(3) up-regulated expression of the tumor suppressor p53 in normal fibroblasts. This up-regulation of p53, however, was observed in all mutant fibroblasts, including those with no VDR, and with Ab099; therefore, VDR and ERp57 are not essential for p53 regulation. The data implicate the VDR and ERp57 as critical components for actions of 1,25-(OH)(2)D(3) against DNA damage, but the VDR does not require normal DNA binding or classical ligand binding to mediate photoprotection. PMID- 22322600 TI - Tannic acid down-regulates the angiotensin type 1 receptor through a MAPK dependent mechanism. AB - In the present study, we investigated the effects of tannic acid (TA), a hydrolysable polyphenol, on angiotensin type 1 receptor (AT1R) expression in continuously passaged rat liver epithelial cells. Under normal conditions, exposure of cells to TA resulted in the down-regulation of AT1R-specific binding in concentrations ranging from 12.5-100 MUg/ml (7.34-58.78 MUm) over a time period of 2-24 h with no change in receptor affinity to angiotensin II (AngII). The inhibitory effect of TA on AT1R was specific and reversible. In TA-treated cells, we observed a significant reduction in AngII-mediated intracellular calcium signaling, a finding consistent with receptor down-regulation. Under similar conditions, TA down-regulated AT1R mRNA expression without changing the rate of mRNA degradation, suggesting that TA's effect is mediated through transcriptional inhibition. Cells expressing recombinant AT1R without the native promoter show no change in receptor expression, whereas a pCAT reporter construct possessing the rat AT1R promoter was significantly reduced in activity. Furthermore, TA induced the phosphorylation of MAPK p42/p44. Pretreatment of the cells with a MAPK kinase (MEK)-specific inhibitor PD98059 prevented TA-induced MAPK phosphorylation and down-regulation of the AT1R. Moreover, there was no reduction in AngII-mediated intracellular calcium release upon MEK inhibition, suggesting that TA's observed inhibitory effect is mediated through MEK/MAPK signaling. Our findings demonstrate, for the first time, that TA inhibits AT1R gene expression and cellular response, suggesting the observed protective effects of dietary polyphenols on cardiovascular conditions may be, in part, through inhibition of AT1R expression. PMID- 22322601 TI - Imported strongyloidiasis: epidemiology, presentations, and treatment. AB - Strongyloidiasis is extremely more frequent in immigrants than in travellers. Clinical presentations do not differ significantly between the two groups, and the most frequent picture is a chronic infection characterized by intermittent, mild, non-specific symptoms. Acute presentation is rare but it has been reported in travellers. Screening of asymptomatic subjects is not generally recommended, while a presumptive treatment with ivermectin might be justified for all travellers and immigrant patients presenting unexplained eosinophilia and/or compatible symptoms, even in case of negative test results. In fact, delayed diagnosis and treatment has life-threatening consequences in patients with conditions predisposing to development of hyperinfection and dissemination. PMID- 22322602 TI - Interobserver reliability of baseline noncontrast CT Alberta Stroke Program Early CT Score for intra-arterial stroke treatment selection. AB - BACKGROUND AND PURPOSE: Early ischemic changes on pretreatment NCCT quantified using ASPECTS have been demonstrated to predict outcomes after IAT. We sought to determine the interobserver reliability of ASPECTS for patients with AIS with PAO and to determine whether pretreatment ASPECTS dichotomized at 7 would demonstrate at least substantial kappa agreement. MATERIALS AND METHODS: From our prospective IAT data base, we identified consecutive patients with anterior circulation PAO who underwent IAT over a 6-year period. Only those with an evaluable pretreatment NCCT were included. ASPECTS was graded independently by 2 experienced readers. Interrater agreement was assessed for total ASPECTS, dichotomized ASPECTS (<= 7 versus >7), and each ASPECTS region. Statistical analysis included determination of Cohen kappa coefficients and concordance correlation coefficients. PABAK coefficients were also calculated. RESULTS: One hundred fifty-five patients met our study criteria. Median pretreatment ASPECTS was 8 (interquartile range 7-9). Interrater agreement for total ASPECTS was substantial (concordance correlation coefficient = 0.77). The mean ASPECTS difference between readers was 0.2 (95% confidence interval, -2.8 to 2.4). For dichotomized ASPECTS, there was a 76.8% (119/155) observed rate of agreement, with a moderate kappa = 0.53 (PABAK = 0.54). By region, agreement was worst in the internal capsule and the cortical areas, ranging from fair to moderate. After adjusting for prevalence and bias, agreement improved to substantial or near perfect in most regions. CONCLUSIONS: Interobserver reliability is substantial for total ASPECTS but is only moderate for ASPECTS dichotomized at 7. This may limit the utility of dichotomized ASPECTS for IAT selection. PMID- 22322603 TI - Survival analysis of patients with high-grade gliomas based on data mining of imaging variables. AB - BACKGROUND AND PURPOSE: The prediction of prognosis in HGGs is poor in the majority of patients. Our aim was to test whether multivariate prediction models constructed by machine-learning methods provide a more accurate predictor of prognosis in HGGs than histopathologic classification. The prediction of survival was based on DTI and rCBV measurements as an adjunct to conventional imaging. MATERIALS AND METHODS: The relationship of survival to 55 variables, including clinical parameters (age, sex), categoric or continuous tumor descriptors (eg, tumor location, extent of resection, multifocality, edema), and imaging characteristics in ROIs, was analyzed in a multivariate fashion by using data mining techniques. A variable selection method was applied to identify the overall most important variables. The analysis was performed on 74 HGGs (18 anaplastic gliomas WHO grades III/IV and 56 GBMs or gliosarcomas WHO grades IV/IV). RESULTS: Five variables were identified as the most significant, including the extent of resection, mass effect, volume of enhancing tumor, maximum B0 intensity, and mean trace intensity in the nonenhancing/edematous region. These variables were used to construct a prediction model based on a J48 classification tree. The average classification accuracy, assessed by cross validation, was 85.1%. Kaplan-Meier survival curves showed that the constructed prediction model classified malignant gliomas in a manner that better correlates with clinical outcome than standard histopathology. CONCLUSIONS: Prediction models based on data-mining algorithms can provide a more accurate predictor of prognosis in malignant gliomas than histopathologic classification alone. PMID- 22322604 TI - Cilostazol prevents progression of asymptomatic carotid artery stenosis in patients with contralateral carotid artery stenting. AB - BACKGROUND AND PURPOSE: The progression of atherosclerosis is related to various factors. Although antiplatelet therapy is used for the management of acute ischemic stroke and for the prevention of recurrent stroke, the antiplatelet agent cilostazol may also reduce restenosis after stent implantation in any vessel. This study was performed to assess the impact of cilostazol on plaque progression in the carotid artery contralateral to a stented artery. MATERIALS AND METHODS: Ninety-five patients who underwent contralateral CAS who also had ipsilateral 0%-79% ICS were enrolled. ICS was assessed by duplex sonography every 6 months and by MR imaging/angiography, and digital subtraction angiography if necessary, every 12 months according to the NASCET method. Patient age, sex, past history, and perioperative medical conditions were recorded. RESULTS: While 22.1% of patients experienced disease progression, symptomatic ipsilateral stroke occurred in only 1.1% of patients over 36.2 +/- 18.8 months. On multivariate analysis, precarotid stenosis (HR per 10% increase, 2.08; 95% CI, 1.43-3.05; P < .001) and cilostazol use (HR 0.16; 95% CI, 0.03-0.85; P = .03) were independent predictors for the progression of ICS. CONCLUSIONS: A higher degree of initial stenosis is associated with progression of asymptomatic ICS. Cilostazol may reduce the rate of disease progression in patients with asymptomatic ICS. PMID- 22322605 TI - The Role of preload and leakage correction in gadolinium-based cerebral blood volume estimation determined by comparison with MION as a criterion standard. AB - BACKGROUND AND PURPOSE: Contrast extravasation in DSC-MRI potentiates inaccurate and imprecise estimates of glioma rCBV. We tested assertions that preload and postprocessing algorithms minimize this error by comparing Gd-rCBV using permutations of these 2 techniques with criterion standard rCBV using MION, an intravascular agent. MATERIALS AND METHODS: We imaged 7 Fisher rats with 9L gliosarcomas, by using 3T gradient-echo DSC-MRI with MION (2.0 mg Fe/kg) and staged injection of Gd-diethylene triamine pentaacetic acid: a 0.1-mmol/kg bolus provided no preload (P-) data and served as preload (P+) for a subsequent 0.2 mmol/kg bolus. We computed MION-rCBV (steady-state DeltaR2*, tumor versus normal brain) and Gd-rCBV DeltaR2* [t] integration) without (C-) and with (C+) postprocessing correction, thereby testing 4 correction permutations: P-C-, P-C+, P+C-, and P+C+. We tested whether each permutation reduced bias and variance of the Gd/MION rCBV differences by using generalized estimating equations and Fmax statistics (P < .05 significant). RESULTS: Gd-rCBV progressively better approximated MION-rCBV with increasing leakage correction. There was no statistically significant bias for the mean percentage deviation of Gd-rCBV from MION-rCBV for any correction permutation, but there was significantly reduced variance by using P+C- (22-fold), P-C+ (32-fold), and P+C+ (267-fold) compared with P-C-. P+C+ provided significant additional variance reduction compared with P+C- (12-fold) and P-C+ (8-fold). Linear regression of Gd-rCBV versus MION-rCBV revealed P+C+ to have the closest slope and intercept compared with the ideal, substantially better than P+C-. CONCLUSIONS: Preload and postprocessing correction significantly reduced the variance of Gd-rCBV estimates, and bias reduction approached significance. Postprocessing correction provide significant benefit beyond preload alone. PMID- 22322606 TI - Recanalization with Wingspan stent for acute middle cerebral artery occlusion in failure or contraindication to intravenous thrombolysis: a feasibility study. AB - BACKGROUND AND PURPOSE: Recanalization with the Wingspan stent, which can be deployed rapidly and safely, is an option for treating acute ischemic stroke when intravenous thrombolysis has failed or is contraindicated. This study was performed to evaluate feasibility, efficacy, and safety of recanalization for acute middle cerebral artery occlusion using the Wingspan stent. MATERIALS AND METHODS: We collected 10 patients with acute MCA occlusion in whom recanalization was not achieved with a standard intravenous thrombolysis, or who were ineligible for intravenous thrombolysis, or who presented after 3 hours of symptom onset and in whom the stent placement could be completed within 8 hours from symptom onset. We analyzed angiographic and clinical results. RESULTS: Successful recanalization with the Wingspan stent was achieved in all patients. The mean NIHSS score on admission was 12.7 points (range 4-21). The occlusion sites were located in the 1st segment (n = 7; 2 left, 5 right) and 2nd segment (n = 3, all right) of the MCA. The mean time interval from stroke symptom onset to stent placement was 344.8 +/- 76.3 minutes. No intracranial hemorrhage, vessel perforations, or dissections occurred in any patient. Nine patients improved on the NIHSS at 7 days. One patient did not have a change in the NIHSS score, even though the occluded artery was completely recanalized. At 7 days, the NIHSS score of all patients was 4.4 +/- 4.7 (median 4, range 0-13). At discharge, an mRS of <= 3 was achieved in all patients and an mRS of <= 2 was achieved in 7 patients (70%). CONCLUSIONS: This small case series demonstrates the feasibility of using the Wingspan stent safely and effectively for MCA occlusions when standard treatments are ineffective or not available. PMID- 22322607 TI - Results of screening for intracranial aneurysms in patients with coarctation of the aorta. AB - BACKGROUND AND PURPOSE: IAs are found in 2.3% of adults; the mean age at detection is 52 years. Prevalence is <0.5% in young adults. Early studies suggest that 10%-50% of patients with aortic coarctation have IAs. Screening recommendations are variable. We sought to examine the prevalence of IAs through screening with MRA. MATERIALS AND METHODS: Consecutive patients older than 16 years of age with coarctation undergoing brain MRA between May 1999 and October 2007 were included. MRA was performed by using a 1.5T scanner with a 3D time-of flight protocol; simultaneous MR imaging was performed of the heart and aorta. Cerebral MRAs were double-reported by a neuroradiologist. Statistics are described as mean +/- SD and median +/- range. Continuous variables were compared by using Student t tests and Mann-Whitney U tests (categoric variables, by using the Fisher exact test). RESULTS: One hundred seventeen MRAs were double-reported. The median age was 29 +/- 11 years (range, 16-59 years). IAs were found in 12 patients (10.3%). The mean diameter of IAs was 3.9 mm (range, 2.0-8.0 mm). Patients with aneurysms were older (median, 37 years; range, 16-50 years) than those without (median, 23 years; range, 16-59 years; Z = -2.01, P = .04). Hypertension was more common in those with IAs (IA 83% versus no IA 43%, P = .01). There was no association between ascending aortopathy, bicuspid aortic valves, and IAs. CONCLUSIONS: Patients with coarctation have a higher prevalence of IAs, occurring at an earlier age than in population studies. Whether routine screening is appropriate for this group of patients is unclear. Hypertension is likely to be an important pathophysiologic factor. PMID- 22322608 TI - Radiation dose reduction in temporal bone CT with iterative reconstruction technique. AB - BACKGROUND AND PURPOSE: Iterative reconstruction of CT images is characterized by reduced image noise and may allow reduction in radiation exposure. We investigated the influence of an IRT technique on image quality and radiation dose savings when applied to temporal bone CT. MATERIALS AND METHODS: Based on the typical image quality level of adult subjects using routine radiation dose and FBP, an exsomatized cadaveric head with CNR characteristics closest to the level of clinical subjects was identified. Cadaver acquisitions were performed at multiple levels of tube current exposure. Reconstructions were performed using FBP and IRT (iDose), with multiple iDose levels applied for each acquisition. Transverse and coronal reformations of all reconstructions were evaluated subjectively and objectively. Phantom tests were performed to validate the protocol optimizations with iDose, specifically the spatial resolution relative to routine dose acquisitions. Finally, the results of protocol optimization with iDose were clinically validated in 50 patients. RESULTS: At the same radiation dose, the image CNR of iDose reconstructions was higher than that of FBP and progressively increased with higher iDose levels. The combination of 100 mAs/section and iDoseL5 was the lowest dose that met the requirements for diagnostic acceptability, with CNR slightly higher than our routine institution protocol of 200 mAs/section with FBP reconstruction. Spatial resolution characteristics were similar between FBP and iDose at all different strengths. The findings were consistent among the cadaver, phantom, and clinical acquisitions. CONCLUSIONS: The iDose IRT can help reduce radiation dose of temporal bone CT by 50% relative to routine institution protocols with FBP, while maintaining diagnostic image quality. PMID- 22322609 TI - Proteomic analysis of aneurysm healing mechanism after coil embolization: comparison of dense packing with loose packing. AB - BACKGROUND AND PURPOSE: In clinical practice, durability of occlusion following coil embolization is superior in densely packed, compared with loosely packed, aneurysms. In a rabbit model, we probed, by using proteomics tools, the biologic mechanisms associated with densely packed and completely occluded aneurysms, compared with loosely packed and incompletely occluded aneurysms, to explore the biologic mechanisms of intra-aneurysmal healing following embolization. MATERIALS AND METHODS: Elastase-induced, saccular aneurysms were created in 24 rabbits. Aneurysms were allowed to mature, after which aneurysms were either densely (packing attenuation >25%) or loosely (packing attenuation <20%) packed with platinum coils by endovascular means. After 2 weeks (n = 6 for both groups) and 4 weeks (n = 6 for both groups) of implantation, aneurysm samples harboring coils were harvested. Soluble proteins were extracted from the necks and domes of aneurysms, and proteins were studied using proteomics and bioinformatics tools. RESULTS: In dome tissue, 128 proteins at 2 weeks, and 8 proteins at 4 weeks, were differentially expressed in densely packed, compared with loosely packed, aneurysms. In the neck tissue, 2 proteins at 4 weeks were differentially expressed in densely packed aneurysms. Specific pathway analysis revealed that compared with loosely packed aneurysms, densely packed aneurysms were associated with up-regulation of cell-to-cell signaling and cell adhesion at 2 weeks. Conversely, at 4 weeks, densely packed aneurysms showed a decrease in the expression of structural proteins compared with loosely packed aneurysms. CONCLUSIONS: These findings may focus efforts on specific targets aimed at improving the long-term healing of intracranial, saccular aneurysms. PMID- 22322610 TI - CT fluoroscopy-guided cervical interlaminar steroid injections: safety, technique, and radiation dose parameters. AB - BACKGROUND AND PURPOSE: Cervical epidural steroid injections are approached with trepidation because of concerns over safety, including direct spinal cord injury. CT fluoroscopy is an alternative to conventional fluoroscopy that could potentially help reduce the risk of injury by providing improved localization of the needle tip. We sought to determine rates of technical success and risk of complications in our initial cohort of patients treated with cervical interlaminar ESI performed under CTF guidance. MATERIALS AND METHODS: In this retrospective case series, we reviewed procedural details and CTF images of 53 consecutive cervical interlaminar ESIs performed on 50 patients over a period of 8 months. Rates of technical success, incidence of complications, procedure times, and factors that influence radiation exposure were examined. RESULTS: No symptomatic procedural complications were observed. A single case of intrathecal contrast injection was observed, from which the patient was asymptomatic. The remaining injections were all technically successful. Injections were performed at every cervical level, as high as C1-C2. Total procedure times averaged less than 20 minutes. Average CT fluoroscopic time was 24 seconds and median tube current was 70 mA. CONCLUSIONS: CTF-guided cervical interlaminar ESI can be performed at all levels in the cervical spine with a low rate of procedural complications. Short total procedure times, CT-fluoroscopy times, and reduced tube current make this procedure a practical alternative to cervical ESI performed under conventional fluoroscopy. PMID- 22322611 TI - Dynamic changes in the dural sac cross-sectional area on axial loaded MR imaging: is there a difference between degenerative spondylolisthesis and spinal stenosis? AB - BACKGROUND AND PURPOSE: Axial loaded MR imaging, which can simulate the spinal canal of patients in a standing position, demonstrates a significant reduction of the DCSA compared with conventional MR imaging and provides valuable imaging findings in the assessment of the lumbar spinal canal. The purpose of this study was to compare the DCSA on axial loaded MR imaging between patients with DS and SpS. MATERIALS AND METHODS: Eighty-eight consecutive patients were divided into DS and SpS groups. DCSA on conventional MR imaging and axial loaded MR imaging and changes in the DCSA induced by axial loading were compared between DS and SpS groups. The prevalence of a significant change (>15 mm(2)) in the DCSA was compared between the 2 groups. RESULTS: Axial loaded MR imaging demonstrated significantly smaller DCSA in the DS group (35 +/- 22 mm(2)) than in the SpS group (50 +/- 31 mm(2)), though conventional MR imaging did not show any differences between the 2 groups. The change in the DCSA induced by axial loading was significantly larger in the DS group (17 +/- 12 mm(2)) compared with the SpS group (8 +/- 8 mm(2)). The prevalence of a >15-mm(2) change in the DCSA was significantly higher in the DS group (62.5%) than in the SpS group (16.7%) (odds ratio, 8.33; 95% confidence interval, 3.09-22.50). CONCLUSIONS: Axial loaded MR imaging demonstrated significantly larger changes in the DCSA in patients with DS compared those with SpS. A significant change in the DCSA was more frequently observed in patients with DS. Axial loaded MR imaging may therefore be a more useful tool to decrease the risk of underestimating the spinal canal narrowing in patients with DS than in those with SpS. PMID- 22322612 TI - Hospitalization costs for endovascular and surgical treatment of ruptured aneurysms in the United States are substantially higher than Medicare payments. AB - BACKGROUND AND PURPOSE: Endovascular and surgical options are both available for treatment of ruptured cerebral aneurysms. Knowledge of the costs relative to Medicare reimbursement for hospitalization of these patients is important for understanding the economic impact of these patients on hospitals. MATERIALS AND METHODS: Using the NIS, we identified hospitalizations for clipping and coiling of ruptured cerebral aneurysms from 2001 to 2008 by cross-matching ICD-9 codes for diagnosis of ruptured aneurysm with procedure codes for clipping or coiling of cerebral aneurysms. Hospital costs for 2008 were correlated with age, sex, and discharge status. For discharges of Medicare patients, we compared Medicare payments with costs for respective MS-DRG. RESULTS: For 2008, the average Medicare payment for craniotomy and endovascular intracranial procedures without complication (MS-DRG 22) was $30,380. Medicare discharges with DRG 22, for patients undergoing clipping had median costs of $59,799 in 2008. Those undergoing coiling had median costs of $36,543. Reimbursement for discharges with complications or comorbidities (MS-DRG 21) was $36,304. Median costs for hospitalization of clipped patients with MS DRG 21 was $79,916 and for coiled patients, $56,910. Reimbursement for MS-DRG 20 (major complications or comorbidities) was $41,748, with patients undergoing clipping incurring a median cost of $83,737 and those undergoing coiling incurring a median cost of $83,277. CONCLUSIONS: Hospitalization costs for patients undergoing clipping and coiling of unruptured cerebral aneurysms are substantially higher than Medicare payments. PMID- 22322613 TI - Relationship between tumor enhancement, edema, IDH1 mutational status, MGMT promoter methylation, and survival in glioblastoma. AB - BACKGROUND AND PURPOSE: Both IDH1 mutation and MGMT promoter methylation are associated with longer survival. We investigated the ability of imaging correlates to serve as noninvasive biomarkers for these molecularly defined GBM subtypes. MATERIALS AND METHODS: MR imaging from 202 patients with GBM was retrospectively assessed for nonenhancing tumor and edema among other imaging features. IDH1 mutational and MGMT promoter methylation status were determined by DNA sequencing and methylation-specific PCR, respectively. Overall survival was determined by using a multivariate Cox model and the Kaplan-Meier method with a log rank test. A logistic regression model followed by ROC analysis was used to classify the IDH1 mutation and methylation status by using imaging features. RESULTS: MGMT promoter methylation and IDH1 mutation were associated with longer median survival. Edema levels stratified survival for methylated but not unmethylated tumors. Median survival for methylated tumors with little/no edema was 2476 days (95% CI, 795), compared with 586 days (95% CI, 507-654) for unmethylated tumors or tumors with edema. All IDH1 mutant tumors were nCET positive, and most (11/14, 79%) were located in the frontal lobe. Imaging features including larger tumor size and nCET could be used to determine IDH1 mutational status with 97.5% accuracy, but poorly predicted MGMT promoter methylation. CONCLUSIONS: Imaging features are potentially predictive of IDH1 mutational status but were poorly correlated with MGMT promoter methylation. Edema stratifies survival in MGMT promoter methylated but not in unmethylated tumors; patients with methylated tumors with little or no edema have particularly long survival. PMID- 22322614 TI - Incidence of extrinsic compression of the internal jugular vein in unselected patients undergoing CT angiography. AB - BACKGROUND AND PURPOSE: Little is known about how commonly the internal jugular vein is compressed by extrinsic structures in the upper neck. The purpose of this paper was to identify the frequency and cause of external compression of the superior segment of the internal jugular vein. MATERIALS AND METHODS: Retrospective review of CT angiograms of the neck was performed in 108 consecutive patients. Axial source images were evaluated for moderate (>50%) or severe (>80%) stenosis of the internal jugular vein on the basis of external compression. The cause of extrinsic compression was also recorded. In cases with stenosis, the presence of ipsilateral isoattenuated collateral veins was recorded and considered representative of collateral flow. RESULTS: Moderate stenosis was seen in 33.3% of right and 25.9% of left internal jugular veins. Severe stenosis was seen in 24.1% of right and 18.5% of left internal jugular veins. The most common causes of extrinsic compression included the styloid process and the posterior belly of the digastric muscle. In patients with severe internal jugular vein stenosis, 53.8% of right sides and 55% of left sides had associated condylar collaterals. CONCLUSIONS: Extrinsic compression of the superior segment of the internal jugular vein is a common finding in unselected patients, often caused by the styloid process or the posterior belly of the digastric muscle. Presence of severe stenosis is not universally associated with collateral formation. PMID- 22322615 TI - Diffusion-weighted MR imaging in head and neck cancer: comparison between half fourier acquired single-shot turbo spin-echo and EPI techniques. AB - BACKGROUND AND PURPOSE: Several studies have reported on the clinical utility of DWI in head and neck cancer, but none of these studies compared HASTE with EPI DWI in patients with head and neck cancer. The aim of our study was to compare detection and delineation of primary tumors and lymph nodes by using HASTE and EPI-DWI techniques in patients with HNSCC. MATERIALS AND METHODS: Twelve patients with HNSCC and a total of 12 primary tumors and 77 visualized lymph nodes on MR imaging underwent DWI by using both EPI-based and HASTE techniques. Interobserver agreement for detection, delineation, and ADC values of primary tumors and lymph nodes was assessed by 2 radiologists, and artifacts for both DWI techniques were described. RESULTS: The number of lesions (primary tumors and lymph nodes) identified on pretreatment EPI-DWI was higher compared with pretreatment HASTE DWI, with means of total lesions of 88.5 and 69.0, respectively. Delineation of lesions was also better on pretreatment EPI-DWI compared with pretreatment HASTE DWI, with means of well-delineated lesions of 80.5 and 27.5, respectively. Both EPI- and HASTE-DWI showed good interobserver agreement between radiologists of ADC values in lesions with ICC values of 0.79 and 0.92, respectively. Intraobserver agreement for ADC values in lesions assessed with EPI- versus HASTE DWI techniques was low, with ICC values of 0.31 and 0.42, respectively. Significant interobserver disagreement concerning detection was only seen with HASTE-DWI, and none of the DWI techniques showed significant interobserver disagreements regarding delineation. EPI-DWI was more prone to susceptibility artifacts than HASTE-DWI: Ninety-one percent of primary tumors and 16% of lymph nodes were affected by susceptibility artifacts on pretreatment EPI-DWI, whereas these artifacts were not seen on HASTE-DWI. CONCLUSIONS: Primary tumors and lymph nodes are more easily visualized on EPI-DWI compared with HASTE-DWI. EPI-DWI has geometric distortion, however, which has a negative effect on interobserver agreement of ADC values. PMID- 22322616 TI - Hospital Outpatient Prospective Payment System. AB - A brief review of the Hospital Outpatient Prospective Payment System (HOPPS) is presented highlighting the program's legislative history, outpatient service classifications and payment plan. Specifically, HOPPS measures applicable to imaging practices are discussed. Resources are also provided for further information on the program requirements and the ambulatory payment classifications (APC) system. PMID- 22322617 TI - CT angiography source images with modern multisection CT scanners: delay time from contrast injection to imaging determines correlation with infarct core. PMID- 22322618 TI - Clot characterization by noncontrast CT to predict IV tPA failure. PMID- 22322619 TI - Cryptococcus neoformans: the model organism for yeast antifungal drug susceptibility testing. AB - We describe an approach to antifungal susceptibility testing of the yeast Cryptococcus neoformans that shows promise for predicting the mycological response in patients to treatment. Quantitative cultures of the cerebrospinal fluid provide a direct measure of the patient's mycological response to treatment and have been used in multiple studies to identify the most promising antifungal drugs for subsequent testing in larger clinical studies. Using these quantitative measures of response, a modified macrobroth dilution assay system shows the potential for predicting the response of an individual patient to treatment with amphotericin B, fluconazole, or the combination of amphotericin B plus flucytosine. We describe this modified macrobroth dilution assay method, the statistical approach for assessing susceptibility, and the clinical decisions that can be guided by this in vitro antifungal drug susceptibility testing. PMID- 22322620 TI - [Prevention of complications after percutaneous coronary interventions with statins]. AB - Lipid lowering therapy with statins reduces the risk of cardiovascular events in patients with coronary artery disease. Recent in vitro and in vivo studies demonstrated LDL-independent action of this class of drugs, which appears in modulating endothelial function, inflammation and thrombosis. Periprocedural myocardial infarction and contrast induced nephropathy after percutaneous coronary intervention (PCI), associated with worse outcome on short and long term follow-up, are both complications related to inflammatory pathogenetic mechanisms. Randomized studies showed a beneficial effect of short-term statin pretreatment in reducing peri-procedural cardiac markers release in patients undergoing PCI. In fact, statin therapy before elective PCI reduced periprocedural myocardial infarction in patients with stable angina. Furthermore, an acute loading with high-dose atorvastatin prevented myocardial damage in patients with acute coronary syndromes undergoing early PCI (<48 hours). In patients already on chronic statin therapy, a reload with high dose statin was associated with a significant improvement on 30-day cardiac outcome. Finally, statin therapy at the time of PCI significantly decreased the incidence of contrast-induced nephropathy. All these evidences support an "upstream administration" of short-term, high-dose statins in all patients undergoing PCI, in order to achieve pleiotropic, LDL-independent effects of these drugs. PMID- 22322621 TI - [beta-blockers: a new and emerging treatment for melanoma]. AB - Recent studies have underlined the innovative theories concerning the role of neuroendocrine system on the tumor and metastasis microenvironment. These observations have suggested the possibility that drugs originally intended for the treatment of cardiovascular disease, the beta-adrenergic receptor blockers (beta-blockers), may provide new therapeutic opportunities for the control of tumor progression. A large number of observational studies showed the protective effect of beta-blockers in breast cancer, but more recently, similar findings were also reported in other cancers such as prostate cancer and melanoma. The results of these studies have shown that the use of beta-blockers, but not other antihypertensive drugs, was associated with a significant increase of the disease free survival and of the overall survival. With regard to melanoma, a recent study by De Giorgi et al. showed a 36% reduction in risk of disease progression for each year of treatment with beta-blockers. These data, originating from prospective studies, cannot be considered conclusive and require validation by means of clinical trials that are underway. PMID- 22322622 TI - [Beyond the convention: a qualitative survey inside the Sannio primary care Centres]. AB - Beyond the convention:a qualitative survey inside the Sannio primary care Centres.Within primary care, multidisciplinary team working is essential to promote and maintain the health whilst improving service effectiveness. This study aims to explore the effects of the new organisation of the primary care on the professional and emotional level of the professionals working in the three primary care Centres in Sannio, Benevento, utilizing the focus group technique. Our findings show the professional and organizational effort of primary care professionals to change working methods and tools. Despite teamwork being an efficient and productive way of achieving goals and results, several barriers exist that hinder its potential from becoming fully exploited. PMID- 22322623 TI - [Lung ultrasound imaging of H1N1 influenza]. AB - We describe the case of a 8 year-old child with acute respiratory distress syndrome (ARDS) during H1N1 swine flu. Lung ultrasound performed at the time of admission showed a typical ARDS ultrasound pattern, with multiple sonographic signs of interstitial oedema (also known as B-lines or ultrasound lung comets), and diffuse bilateral sub-pleural lung consolidations. After five days of anti viral therapy, lung ultrasound showed a reduction of the dimension of consolidations, not clearly visible at chest X-ray, helping in the management of the patient. PMID- 22322624 TI - [General practice in Italy: from individual practice to multi-professional collaboration]. AB - In Public Health, the multiprofessional team is became essential to guarantee high quality levels of performances. General Practice, which is the basic element of the primary health care, has urgently to undertake a way which could lead it from voluntary associationism to obligatory aggregation and then to the construction of a motivation/convenience system which correlate individuals to the team activity. PMID- 22322625 TI - [Primary health care in Italy: from medical behaviour to teamwork]. AB - Primary health care represents an essential area in relation to health protection: its purposes are, on the one hand, health promotion, on the other hand the possibility to resort only if necessary to hospital care. In the novel National Collective Agreement, new teamwork forms of organization are introduced; for example, the obligatory Territorial Functional Aggregation: an organizational Unit which general practitioners and general paediatricians join to. The article by Scala et al. (see page 17), about an experience of primary health care, focuses the necessity to plan new organizational forms of work for teams oriented to realize efficient and effective answers to population needs: the phases of the activities in equipe are analysed, lingering on lights and shadows of the team. PMID- 22322626 TI - [Role of stem cells in the pathogenesis of chronic obstructive pulmonary disease and of pulmonary emphysema]. AB - There are only few human translational studies performed in the area of stem cell research in patients with chronic obstructive pulmonary disease (COPD) and/or pulmonary emphysema. Before progress to clinical trials with stem cells we believe that more human translational studies are necessaries, otherwise the clinical rationale would be solely based on limited in vitro and animal studies. In the future, stem cell therapy could be a treatment for this disease. Currently, stem cell therapy is still to be considered as an area of active research, lacking a strong rationale for performing clinical trials in COPD. Although stem cells would be likely to represent a heterogeneous population of cells, the different cell subsets and their importance in the pathogenesis of the different clinical phenotypes need to be fully characterised before progressing to clinical trials. Moreover, the potential side effects of the stem cell therapy are often underestimated. We should not ignore that some of the most deadly neoplasms are arising from stem cells. PMID- 22322627 TI - New alternatively spliced variant of prostate-specific membrane antigen PSM-E suppresses the proliferation, migration and invasiveness of prostate cancer cells. AB - PSM-E is a newly discovered alternatively spliced variant of prostate-specific membrane antigen (PSMA). In the current study, its role on the proliferation, invasiveness and migration in prostate cancer cell lines was analyzed. PSM-E and PSMA (as a comparison) eukaryotic expression vectors pcDNA3.0/PSM-E and pcDNA3.0/PSMA were constructed, validated by RT-PCR and Western blotting, and PSMA/PSM-E overexpression PC-3 cell models were built. Gene interference was used to block PSMA and the expression of its splice variants in LNCap cells. Three shRNA fragments were synthesized against PSMA, cloned into the vector pSilencer 2.1-U6-neo, their interference effect was evaluated by RT-PCR and Western blotting, and pSilencer 2.1-U6-neo-shRNA3 (named p-shRNA3) was chosen in further analyses. Growth curves were drawn to observe the proliferation change, which showed that PSM-E had the potential to suppress proliferation (P<0.05), but no significant change was observed in PSMA/PC-3 cells and in PSMA/PSM-E interfering LNCap cells (P>0.05). Cross-river test showed that the migration speeds of PSM E/PC-3 and PSMA/PC-3 were both significantly slower than the vector negative control, and faster in p-shRNA3 interfering LNCap cells compared with its vector negative control (P<0.05), and no significant difference existed between PSM-E/PC 3 and PSMA/PC-3 (P>0.05). Transwell assay showed that the invasive cells of both PSMA/PC-3 and PSM-E/PC-3 were fewer compared to the vector negative control (P<0.05), and the invasive suppression effect of PSM-E was weaker than PSMA (P<0.05), and accordingly, invasiveness of interfering LNCaP cells was enhanced compared with the vector negative control (P<0.05). These results showed that PSM E could suppress proliferation, migration and invasiveness of prostate cancer cells. Its suppression effect on cell proliferation is stronger compared to PSMA and the suppression effect on invasiveness is weaker than that of PSMA. PMID- 22322628 TI - Inappropriate arm positioning during scout image acquisition resulting in increased radiation dose while performing a chest CT. PMID- 22322629 TI - Tis the season . . . PMID- 22322630 TI - Latin American foot and ankle surgery today. AB - Latin American medical orthopedic sub specialties have evolved a lot during the past decade. Foot and ankle surgery for instance, has gained high level of proficiency and competence throughout the international scientific communities. This may be due to the availability of new technology in osteosyntheses, orthopedic devices and surgical instruments used to optimize results, regardless of the low economic resources Latin American countries possess. Also, foot and ankle surgery training is being promoted by several International Medical associations that pursuit scientific knowledge and strengthen the practice. Day to day, more Latin American universities offer Fellowships for on-going training. PMID- 22322632 TI - Physical environment design for improving patient safety. PMID- 22322633 TI - An evaluation of operating room safety and efficiency: pilot utilization of a structured focus group format and three-dimensional video mock-up to inform design decision. AB - OBJECTIVE: The purpose of this investigation was to identify safety and efficiency-related design features for inclusion in operating room (OR) construction documents. BACKGROUND: Organizations are confronted with an array of challenges when planning an OR, including inefficiencies in operations, adverse events, and a variety of innovations to choose from. Currently, techniques that can be used in design practice and to inform design decision making for implementable OR solutions are limited. METHODS: The project team used a structured focus group format with mixed methods to solicit 19 varying surgical team members' reactions to a three-dimensional video mock-up of a proposed OR. Data from the 19 participants were analyzed using stepwise multiple regression and content analysis of open-ended responses. RESULTS AND DISCUSSION: Results demonstrate that several features of the proposed OR design predict meaningful outcomes, including flexibility and satisfaction with the OR setup, adverse event prevention, team performance, and distractions and interruptions. Participants' suggested solutions include universal booms to support anesthetic and perfusion capabilities, a fixed circulating nursing workstation that faces the patient and is at the foot of the operating room table, a wall-mounted monitor across from the surgeon, and wiring to support a touch-screen control arm in OR surgical fields. CONCLUSIONS: Findings from structured focus groups with mixed methods lead to implementable design solutions for construction documentation. The expeditious qualities and objectivity of the format are value-adds to the design decision-making process. Future research should use various techniques such as virtual technologies and building information modeling. PMID- 22322634 TI - Environmental congruence and work-related stress in acute care hospital medical/surgical units: a descriptive, correlational study. AB - OBJECTIVE: To describe the degree to which Environmental Congruence (EC) is present in sampled units and considered important/desirable by staff RNs; staff RNs' reported level of work-related stress (WRS); the perceived contribution of the physical environment to WRS; and the relationship between existing levels of EC and WRS. BACKGROUND: Few studies have focused on how the physical environment might contribute to nurses' WRS and chronic nursing shortages. The construct of EC can be used, within a Person Environment (PE)-Fit framework, to assess the fit among nurses, nursing work, the physical work environment, and WRS. METHODS: EC was measured using investigator-developed, literature/criterion-based survey instruments. Staff RNs reported WRS variables by using two single-item self report measures. The final convenience sample consisted of 471 staff RNs from 39 medical/surgical units from 12 hospitals in the upper Midwest. Data were collected over a 7-month period. RESULTS: The mean level of existing EC in the sample was roughly 70% percent of highest capacity and that of important/desired EC in the sample was 93%. Staff RNs' mean level of WRS was 6.7; the mean contribution of the physical environment to WRS was 5.8. Moderate negative correlations were found between EC and WRS (r = -.41, p < .05), and between physical environment contribution to WRS and EC (r = -.55, p <.001). CONCLUSIONS: Staff RNs in the sampled units wanted a significantly higher level of EC. They rated their WRS moderately high and the contribution of the physical environment to it as moderate. A moderately negative relationship was found between EC and WRS. EC may be a useful construct in research that attempts to improve hospital nursing work environments. PMID- 22322635 TI - The impact of bedside technology on patients' well-being. AB - OBJECTIVE: This paper presents a study to gain insight into the effects of the visibility of medical equipment on the well-being of patients. BACKGROUND: Encounters with healthcare situations are characterized by stress and anxiety. The presence of wires, tubes, and monitors near the bedside may contribute to these feelings. One of the trends in healthcare design is to organize the headwalls of patient rooms in such a way as to reduce clutter and minimize the visibility of medical equipment, but no experimental studies are available that investigate the effects of the visibility of medical equipment in patient rooms. METHODS: This experiment employed a single-factor between-subjects design (medical equipment visible vs. medical equipment out of sight) exposing participants (n = 42) to a scenario and a picture of a hospital room. RESULTS: Placing medical equipment out of sight leads to reduced feelings of stress in patients. This stress-reducing effect is mediated by feelings of pleasure. Placing medical equipment out of sight leads to a more positive emotional state, which in turn leads to feelings of reduced stress in patients. Moreover, placing equipment out of sight leads to people having more trust in the healthcare provider. CONCLUSIONS: The current study emphasizes the importance of the built healthcare environment and shows what role the visibility of medical equipment can play in the healing process of patients. PMID- 22322636 TI - Comparison of private room with multiple-bed ward neonatal intensive care unit. AB - OBJECTIVE: This study determined whether a private room or open ward design better met optimal environmental conditions for a neonatal intensive care unit with regard to sound level, light level, temperature and humidity. BACKGROUND: Multiple-bed designs for hospital neonatal intensive care units were the standard until recently. Now, private room designs promise to provide better conditions for neonate development and patient care quality. METHODS: The study compared an eight-bed open ward design with a private room design of a 45-bed neonatal intensive care unit, measuring the environmental parameters of sound, light, temperature, and humidity before and after the construction and occupation of a new private room unit. RESULTS: Average light levels were higher in the private room design because of the increased number of windows, but both designs were within the recommended levels. Mean temperature readings were two degrees cooler in the private room environment, and readings were more stable. Mean humidity readings in the two environments were the same, but humidity levels in the private room design were more stable. Median sound level in the private room design was lower than the open ward design, but the range was similar. CONCLUSION: The private room design allows for a more controlled patient care environment that can be maintained within a smaller range of variation nearer optimal environmental conditions. PMID- 22322637 TI - Saving lives following the expansion of centralized remote telemetry monitoring. AB - Continuous monitoring of patients throughout the hospital is a desirable method to ensure the continuity of quality care. Hospitals looking to improve the manner in which they maintain such continuity without compromising efficiency must explore the benefits of implementing monitoring technology to its fullest potential. This case study chronicles the journey of a level-one trauma hospital during the expansion of remote wireless telemetry monitoring and the telemetry technician role. The lives saved as a result of this expansion were primarily attributable to the installation of remote wireless telemetry monitoring in the emergency department. The expansion of the telemetry technician role improved not only the quality of the monitoring signal and recognition, but also the ability to identify changes in trended data. The next step for improving care delivery includes the addition of a patient locator system within the facility, which will provide the most accurate information regarding patient location during transfer. Accurately identifying patient location in addition to alerting staff to changes in patient status will ensure that care providers respond promptly and that the highest quality of patient care is delivered while patients are away from the nursing unit. PMID- 22322638 TI - Patient safety as the number one priority in healthcare design. PMID- 22322639 TI - Acuity-adaptable nursing care: exploring its place in designing the future patient room. AB - AIM: To substantiate the anticipated benefits of the original acuity-adaptable care delivery model as defined by innovator Ann Hendrich. BACKGROUND: In today's conveyor belt approach to healthcare, upon admission and through discharge, patients are commonly transferred based on changing acuity needs. Wasted time and money and inefficiencies in hospital operations often result-in addition to jeopardizing patient safety. In the last decade, a handful of hospitals pioneered the implementation of the acuity-adaptable care delivery model. Built on the concept of eliminating patient transfers, the projected outcomes of acuity adaptable units-decreased average lengths of stay, increased patient safety and satisfaction, and increased nurses' satisfaction from reduced walking distances make a good case for a model patient room. CONCLUSION: Although some hospitals experienced the projected benefits of the acuity-adaptable care delivery model, sustaining the outcomes proved to be difficult; hence, the original definition of acuity-adaptable units has not fared well. Variations on the original concept demonstrate that eliminating patient transfers has not been completely abandoned in healthcare redesign and construction initiatives. Terms such as flex-up, flex down, universal room, and single-stay unit have since emerged. These variations convolute the search for empirical evidence to support the anticipated benefits of the original concept. To determine the future of this concept and its variants, a significant amount of outcome data must be generated by piloting the concept in different hospital settings. As further refinements and adjustments to the concept emerge, the acuity-adaptable room may find a place in future hospitals. PMID- 22322641 TI - Evolving roles for practice-based researchers. PMID- 22322640 TI - Control and mitigation of healthcare-acquired infections: designing clinical trials to evaluate new materials and technologies. AB - Hospitals clean environmental surfaces to lower microbial contamination and reduce the likelihood of transmitting infections. Despite current cleaning and hand hygiene protocols, hospital-acquired infections (HAIs) continue to result in a significant loss of life and cost the U.S. healthcare system an estimated $45 billion annually. Stainless steel and chrome are often selected for hospital touch surfaces for their "clean appearance," comparatively smooth finish, resistance to standard cleaners, and relative effectiveness for removing visible dirt during normal cleaning. Designers use wood surfaces for aesthetics; plastic surfaces have become increasingly endemic for their relative lower initial cost; and "antimicrobial agents" are being incorporated into a variety of surface finishes.This paper concentrates on environmental surface materials with a history of bactericidal control of infectious agents and focuses on the methods necessary to validate their effectiveness in healthcare situations. Research shows copper-based metals to have innate abilities to kill bacteria in laboratory settings, but their effectiveness in patient care environments has not been adequately investigated. This article presents a research methodology to expand the evidence base from the laboratory to the built environment. For such research to have a meaningful impact on the design/specifying community, it should assess typical levels of environmental pathogens (i.e., surface "cleanliness") as measured by microbial burden (MB); evaluate the extent to which an intervention with copper-based materials in a randomized clinical trial affects the level of contamination; and correlate how the levels of MB affect the incidence of infections acquired during hospital stays. PMID- 22322642 TI - Generating evidence from day-to-day activities: methodological issues-part 1. PMID- 22322644 TI - The design flaws in the new tertiary medical center. PMID- 22322646 TI - Electrocatalytic activity of nanoporous Pd and Pt: effect of structural features. AB - The electrocatalytic activities of nanoporous palladium (npPd) and platinum (npPt) for oxygen reduction reaction (ORR) under alkaline conditions and hydrogen peroxide electrochemical reactions under neutral conditions were examined. npPd and npPt were prepared by the electrochemical deposition of each metal from the corresponding metal precursor in the presence of reverse micelles of Triton X 100, directing highly porous microstructures. The nanoporous catalysts showed excellent electrocatalytic activity for both the ORR and hydrogen peroxide electrochemical oxidation/reduction due to the increased active surface area. In particular, the npPd exhibited superior ORR activity (i.e., more positive onset and half-wave potentials, higher current density and greater number of electrons transferred) despite the smaller roughness factor than the npPt and commercial Pt. The catalytic activity for the hydrogen peroxide electrochemical reactions was also higher while using npPd (i.e., faster electrode reaction kinetics, increased current densities, etc.) compared to npPt. The higher catalytic activity of npPd than that of npPt suggests an advantage of the unique npPd structure, composed of nano- as well as micro-porosity, in facilitating mass transport through the porous metal layer. The npPd exhibited amperometric current responses, induced by the oxidation as well as reduction of hydrogen peroxide, linearly proportional to the hydrogen peroxide concentration with a rapid response time (<~2 s), high sensitivity, and low detection limit (<1.8 MUM). PMID- 22322647 TI - [Adjuvant radiotherapy after radical prostatectomy as preventive treatment for biochemical recurrence]. AB - Adjuvant radiotherapy (RT) has proven to be more effective in patients at high risk of relapse than salvage RT when this relapse occurs. To optimize its use we must identify the subset of patients at greater risk of residual microscopic disease after surgery, since in them the likelihood of 5-10 year biochemical failure can reach 60%. There are many studies on the subject in which these factors are identified, which in general are: presence of positive margins and capsular or seminal vesicle involvement (T3a-b). Of these, it seems that the presence of positive margins is the most powerful predictor of relapse. With regard to radiotherapy, there is variability in the dose to give and volume treated. In general, the dose in most series is >= 60 Gy, reaching some authors up to 70 Gy. As to the association or not hormone therapy (HT) and adjuvant radiotherapy, it is a subject of debate and so far no results of studies demonstrate a sufficient benefit, so it should be individualized, weighing potential benefits in high risk patients against side effects. PMID- 22322648 TI - Tonicity enhancer binding protein (TonEBP) and hypoxia-inducible factor (HIF) coordinate heat shock protein 70 (Hsp70) expression in hypoxic nucleus pulposus cells: role of Hsp70 in HIF-1alpha degradation. AB - The objective of our study was to examine the regulation of hypoxic expression of heat shock protein 70 (Hsp70) in nucleus pulposus cells and to determine if Hsp70 promoted hypoxia-inducible factor (HIF)-1alpha degradation. Rat nucleus pulposus cells were maintained in culture in either 21% or 1% oxygen. To determine the regulation of Hsp70 expression by tonicity enhancer binding protein (TonEBP) and HIF-1/2, loss-of-function and gain-of-function experiments and mutational analysis of the Hsp70 promoter were performed. Hypoxia increased Hsp70 expression in nucleus pulposus cells. Noteworthy, hypoxia increased TonEBP transactivation and mutation of TonE motifs blocked hypoxic induction of the Hsp70 promoter. In contrast, mutation of hypoxia response element (HRE) motifs coupled with loss-of function experiments suggested that HIF-1 and HIF-2 suppressed Hsp70 promoter activity and transcription. Interestingly, HIF-alpha interferes with TonEBP function and suppresses the inductive effect of TonEBP on the Hsp70 promoter. In terms of Hsp70 function, when treated with Hsp70 transcriptional inhibitor, KNK437, there was an increase in HIF-1alpha protein stability and transcriptional activity. Likewise, when Hsp70 was overexpressed, the stability of HIF-1alpha and its transcriptional activity decreased. Hsp70 interacted with HIF-1alpha under hypoxic conditions and evidenced increased binding when treated with MG132, a proteasomal inhibitor. These results suggest that Hsp70 may promote HIF-1alpha degradation through the proteasomal pathway in nucleus pulposus cells. In hypoxic and hyperosmolar nucleus pulposus cells, Hsp70, TonEBP, and HIFs form a regulatory loop. We propose that the positive regulation by TonEBP and negative regulation of Hsp70 by HIF-1 and HIF-2 may serve to maintain Hsp70 levels in these cells, whereas Hsp70 may function in controlling HIF-1alpha homeostasis. PMID- 22322649 TI - Estimating three synaptic conductances in a stochastic neural model. AB - We present a method for the reconstruction of three stimulus-evoked time-varying synaptic input conductances from voltage recordings. Our approach is based on exploiting the stochastic nature of synaptic conductances and membrane voltage. Starting with the assumption that the variances of the conductances are known, we use a stochastic differential equation to model dynamics of membrane potential and derive equations for first and second moments that can be solved to find conductances. We successfully apply the new reconstruction method to simulated data. We also explore the robustness of the method as the assumptions of the underlying model are relaxed. We vary the noise levels, the reversal potentials, the number of stimulus repetitions, and the accuracy of conductance variance estimation to quantify the robustness of reconstruction. These studies pave the way for the application of the method to experimental data. PMID- 22322650 TI - Determinants of altered sensorium at presentation with diabetic ketoacidosis. AB - AIM: The aim of this paper was to determine the prevalence of altered sensorium and their determinants in diabetic ketoacidosis (DKA). METHODS: Retrospective review of medical records for diabetic ketoacidosis admissions over a two year period. RESULTS: A total of 94 admissions for DKA in 89 patients were reviewed. Majority of admissions were female related. The mean age of the subjects was 39.1+/-18.5 years. The prevalence of altered sensorium defined as Glasgow coma scale (GCS) below 15 was 47.9%. In Model 1, systolic blood pressure (SBP) <90 mmHg (odds ratio [OR] 17.5 95% Confidence Interval (CI) 2.1-142.9; P=0.008 and calculated effective serum osmolality >320 mosmol/Kg (OR 3.6 95% CI 1.4-12.2; P=0.043 were independently associated with altered sensorium. In Model 2 where serum osmolality was substituted with uncorrected serum sodium, SBP <90 mmHg OR 19.6 95% CI 2.2-100; P=0.007, uncorrected serum sodium >150 mmol/L OR 18.5 95% CI 2.1-100; P=0.0009 and white cell count >25 x 106/L OR 3.6 95% CI 1.03-13.5; P=0.05 were independently associated with altered sensorium. CONCLUSION: Systolic blood pressure <90 mmHg, calculated effective serum osmolality >320 mosmol/Kg, uncorrected serum sodium >150 mmol/L and white bood count >25 x 106/L were independently associated with altered sensorium. PMID- 22322651 TI - Effect of smoking intensity on thyroid volume, thyroid nodularity and thyroid function: the Melen study. AB - AIM: The purpose of our study was to determine the association between smoking habit, goiter, thyroid functions and ultrasonographic nodularity in moderately iodine deficient area. METHODS: The MELEN study is a prospectively designed survey on the prevalence of thyroid diseases in Turkish adults. A total of 2298 subjects with a mean age of 50 (age range 18 to 92) were interviewed. Smoking habits were registered from questionnaires and subsequent interviews with a physician. Thyroid ultrasonography was performed and interpreted by the same experienced physician, using the same equipment. After an overnight fast, blood samples were collected from all the study subjects for the determination of serum free thyroxine, thyroid stimulating hormone (TSH) were measured. RESULTS: Mean thyroid volumes of current smokers were significantly lower than either former or never smokers (P=0.014). There were no difference according to smoking habits on goiter and established multinodularity in current smokers (P<0.05). Heavy smokers (>20 pack/year) had higher thyroid volumes, higher goiter and multinodular goiter (MNG) prevalence than moderate smokers (P<0.001). Thyrotoxicosis (TSH<0.35) cases were more frequent among heavy smokers than moderate smokers (14.1% versus 8.2%, P<0.001; respectively). Heavy smoking independently predicted goiter (odds ratio: 1.459 [95% confidence interval: 1.029 and 2.068]; P=0.034). CONCLUSION: Heavy smoking was associated with increased prevalence of thyroid multinodularity and goiter in respect to moderate smoking. No association was found between smoking habit and thyroid dysfunction. PMID- 22322652 TI - Gastrointestinal regulation of food intake: do gut motility, enteric nerves and entero-hormones play together? AB - The gastrointestinal system can be considered the gateway for food entry in our body. Rather than being a passive player, it is now clear that gut strongly influence the feeding behavior and contribute to maintain energy balance with different signals. The aim of this review is to summarize the current knowledge about the role of gastrointestinal tract in the control of food intake, by focusing on the interplay existing between the enteric nervous system and gastrointestinal hormones and their ability to modulate digestive motility and sensitivity. Also the latest advances about the contribution of gut microbiota and gastrointestinal taste receptors are described. From the reported data it clearly emerges that gut hormones together with nervous signals likely contribute to the regulation of energy balance and modulate food intake through the control of digestive motility and sensations. The close linkage among gastrointestinal hormones, the gut and the central nervous systems appears very intriguing and has induced the development of a new field of research: the gastroendocrinology. PMID- 22322653 TI - Ovarian function and gastrointestinal motor activity. AB - Gastrointestinal disorders are strictly related to the ovary function. In fact, it is noted that the prevalence of visceral pain disorders such as irritable bowel syndrome, gastroesophageal reflux disease, gallbladder and biliary tract diseases are significantly higher in women. Furthermore, symptom such as nausea, vomiting, abdominal pain, distension, satiety, bloating, diarrhoa or constipation, frequently appears in relation with pregnancy, luteal phase of the menstrual cycle or perimenopausal and menopausal states. Further support for the contribution of ovarian steroids to functional gastrointestinal disorders comes from studies demonstrating that pharmacological ovariectomy reduces abdominal pain symptoms. Therefore, addressing the influence of sex and sex hormones in the modulation of visceral pain appears critical to develop new strategies of diagnosis and therapy sex-directed for gastro-intestinal disorders. PMID- 22322654 TI - Role of serotonin in gastrointestinal physiology and pathology. AB - Serotonin is one of the most abundant molecules in the gastrointestinal tract and it plays a crucial role in the regulation of several physiological functions, such as motility, secretion and visceral sensitivity. Besides this well documented physiological role, increasing evidence supports the concept that 5-HT is directly involved in pathological mechanisms, as well as the modulation of immune/inflammatory responses within the gut. The wide range of pathophysiological actions exerted by 5-HT are mediated by several different serotonergic receptor types and subtypes. Depending on the receptor bound and its localization, 5-HT evokes different and, sometimes, opposite responses. Therapeutic interventions aiming at modulating 5-HT signaling are mainly focused on the development of receptor agonists/antagonists, characterized by high affinity and selectivity for serotonergic receptors in the gut, to avoid the presence of adverse effects in the brain, where 5-HT is important in control mood. This review summarizes the vast current knowledge on 5-HT as a physiological mediator and analyzes the increasing body of literature describing 5-HT signaling abnormalities in functional and inflammatory disorders both in animal models and in humans. Finally, an overview on the therapeutic agents used in clinical practice is provided. PMID- 22322655 TI - Biological aspects of gender disorders. AB - The scientific community is very interested in the biological aspects of gender disorders and sexual orientation. There are different levels to define an individual's sex: chromosomal, gonadic, and phenotypic sex. Concerning the psychological sex, men and women are different by virtue of their own gender identity, which means they recognize themselves as belonging to a determinate sex. They are different also as a result of their own role identity, a set of behaviors, tendencies, and cognitive and emotional attitudes, commonly defined as "male" and "female". Transsexuality is a disorder characterized by the development of a gender identity opposed to phenotypic sex, whereas homosexuality is not a disturbance of gender identity but only of sexual attraction, expressing sexual orientation towards people of the same sex. We started from a critical review of literature on genetic and hormonal mechanisms involved in sexual differentiation. We re-examined the neuro-anatomic and functional differences between men and women, with special reference to their role in psychosexual differentiation and to their possible implication in the genesis of homosexuality and identity gender disorders. Homosexuality and transsexuality are conditions without a well defined etiology. Although the influence of educational and environmental factors in humans is undeniable, it seems that organic neurohormonal prenatal and postnatal factors might contribute in a determinant way in the development of these two conditions. This "organicistic neurohormal theory" might find support in the study of particular situations in which the human fetus is exposed to an abnormal hormonal environment in utero. PMID- 22322656 TI - Resolution of insulin-requiring diabetes in a liver transplant recipient after treatment of a pheochromocytoma: case report and review of literature. AB - The aim of this paper was to report the case of type 2 diabetes and significant insulin resistance that improved dramatically after removal of a pheochromocytoma in a liver transplant recipient , and to provide a review of the relevant literature. We describe the clinical presentation, diagnostic results and management of the patient. In addition, we performed a PubMed search for related English language articles, to provide an overview of the pertinent literature. A 53 year old woman with a history of an orthotopic liver transplantation and insulin-requiring type 2 diabetes was admitted to the hospital with fever, diaphoresis, tachycardia and hypertension. A pheochromocytoma was diagnosed and removed. The patient subsequently developed hypoglycemia and required no further insulin therapy. Pheochromocytomas have been described to lead to hyperglycemia and diabetes, due to the suppression of insulin release and increased insulin resistance. Furthermore, a review of the literature revealed only 3 other reported cases of pheochromocytomas in organ transplant recipients. None of these pheochromocytomas were believed to have occurred de novo after transplantation. This is the first report of a pheochromocytoma in a liver transplant recipient and possibly the first case of a de novo pheochromocytoma in any organ transplant recipient. Moreover, this case showcases pheochromocytomas as a rare cause of diabetes mellitus. PMID- 22322657 TI - Burning mouth syndrome in Parkinson's disease: dopamine as cure or cause? AB - Burning mouth syndrome has been reported as being more common in Parkinson's disease patients than the general population. While the pathophysiology is unclear, decreased dopamine levels and dopamine dysregulation are hypothesized to play a role. We report a patient with Parkinson's disease who developed burning mouth syndrome with carbidopa/levodopa. Our patient had resolution of burning mouth symptoms when carbidopa/levodopa was replaced with a dopamine agonist. Based on our patient's clinical course, in conjunction with earlier studies assessing the relationship between burning mouth syndrome and Parkinson's disease, we discuss a potential role for dopamine in burning mouth syndrome in Parkinson's disease. PMID- 22322658 TI - Effect of transcatheter arterial infusion chemotherapy using iodized oil and degradable starch microspheres for hepatocellular carcinoma. AB - BACKGROUND: Transcatheter arterial infusion chemotherapy (TAI) using a combination of iodized oil (lipiodol) and degradable starch microspheres (DSMs) has been reported to be superior to TAI with either lipiodol or DSMs separately for the treatment of hepatocellular carcinoma (HCC), based on the results of a prospective randomized study. In the study reported here, we investigated the predictors influencing response and survival in HCC patients receiving TAI using lipiodol and DSMs. METHODS: A total of 50 HCC patients [Child-Pugh A/B, 34/16 patients; maximum tumor size 2.9 cm (mean); tumor number <5/>=5 = 29/21 patients] were administered a mixture of cisplatin and lipiodol, followed by the injection of DSMs. RESULTS: According to the criteria of the Liver Cancer Study Group of Japan, the response [complete response (CR) + partial response (PR)] rate and CR rate were 72 and 38%, respectively [CR, 19 patients; PR, 17; stable disease, 9; progressive disease, 5]. The 1-, 2-, 3-, and 4-year cumulative survival rates were 85, 67, 41, and 35%, respectively, and the median survival time was 32.6 months. Multivariate analysis identified tumor number <5 nodules [odds ratio 10.651, 95% confidence interval (CI) 2.168-52.317; P = 0.004] as an independent predictor of response and des-gamma-carboxyprothrombin level <100 mAU/mL [hazard ratio (HR), 0.268, 95% CI 0.091-0.786, P = 0.017] and therapeutic effect CR or PR (HR 0.255, 95% CI 0.099-0.659; P = 0.005) as independent predictors of survival. CONCLUSION: Transcatheter arterial infusion chemotherapy using lipiodol and DSMs might be considered as a potential intervention in HCC patients, especially those with tumors of <5 nodules. PMID- 22322660 TI - Partial normalization of pubertal timing in female mice with DSS colitis treated with anti-TNF-alpha antibody. AB - BACKGROUND: Inflammatory bowel disease (IBD) and resultant colitis occurring prior to puberty are frequently associated with delayed puberty and losses of growth and bone mineralization. Some of this delay may be due to colonic inflammation and associated systemic inflammation. To date no treatments for IBD have been shown to normalize the timing of puberty. Our objective in this study was to determine whether there is a normalization of the timing of puberty during treatment of colitis using monoclonal antibodies (abs) to tumor necrosis factor (TNF)-alpha. METHODS: We induced colitis in 23-day-old C57Bl6 female mice using 3% dextran sodium sulfate (DSS) for 7 days, followed by removal of DSS for an additional 3 days, resulting in 10 days of worsening colitis. DSS-treated mice received either TNF-alpha ab or Control ab on days 4 and 8 of colitis, while non colitic Control mice received injections of TNF-alpha ab (Control + TNF-alpha ab). All groups were followed for the timing of vaginal opening until day of life 33, when they were euthanized for serum and colon collection. RESULTS: The DSS + TNF-alpha ab group had lower levels of systemic interleukin (IL)-6 and a partial normalization of the timing of vaginal opening compared to the DSS + Control ab group. There were no differences in weight gain, growth, or colon histological inflammatory scores between the DSS + TNFalpha ab and DSS + Control ab groups over the course of the experiment. CONCLUSIONS: We conclude that anti-TNF-alpha ab treatment causes a partial normalization of pubertal timing coincident with decreased systemic inflammation in DSS colitis. These data may have implications regarding growth and bone mineralization outcomes in pediatric IBD. PMID- 22322661 TI - Decoupling fluorescence and photochromism in bifunctional azo derivatives for bulk emissive structures. AB - Bifunctional molecules that combine independent push-pull fluorophores and azo photochromes have been synthesized to create fluorescent structures upon light induced migration in neat thin films. Their photochromic and emissive properties have been systematically investigated and interpreted in light of those of the corresponding model compounds. Fluorescence lifetimes and photoisomerization and fluorescence quantum yields have been determined in toluene solution. Kinetic analyses of the femtosecond transient absorption spectra reveal that the fluorophores evolve in a few picoseconds into a distorted intramolecular charge transfer excited state, strongly stabilized in energy. Radiative relaxation to the ground state occurred competitively with the energy-transfer process to the azo moiety. Introduction of a 10 A-long rigid and nonconjugated bridge between the photoactive units efficiently inhibits the energy transfer while it imparts enhanced free volume, which favors photoactivated molecular migration in the solid state. PMID- 22322659 TI - Biopsy interpretation of colonic biopsies when inflammatory bowel disease is excluded. AB - The interpretation of colonic biopsies related to inflammatory conditions can be challenging because the colorectal mucosa has a limited repertoire of morphologic responses to various injurious agents. Only few processes have specific diagnostic features, and many of the various histological patterns reflect severity and duration of the disease. Importantly the correlation with endoscopic and clinical information is often cardinal to arrive at a specific diagnosis in many cases. PMID- 22322662 TI - Montreal's contribution to the Quebec anesthesia workforce: a comparison between anesthesia residents trained at McGill University and those trained at Universite de Montreal. AB - PURPOSE: Alumni from McGill University (MAA) and alumni from Universite de Montreal (UMA) anesthesia residency programs were compared with regard to demographic characteristics and practice location. METHODS: McGill University alumni and UMA (1990-2010) were studied according to age, sex, pre-anesthesia education, fellowship training, advanced research training, and practice location. Logistic regression analysis of demographics in relation to practice location was performed. RESULTS: Alumni were mostly male (MAA [n = 102]; male:female 72 [71%]: 30 [29%] vs UMA [n = 89]; male:female 51 [57%]: 38 [43%]) in their early thirties [mean 32; standard deviation (3.2) and 32 (3.0), respectively]. Approximately 45% of MAA obtained an undergraduate education in provinces other than Quebec compared with 6% of UMA. A majority of alumni from either institution practice in Quebec (MAA 67%; UMA 94%). Of the MAA who received undergraduate education in Quebec, approximately 80% practice in that province compared with approximately 46% of those who were educated in other provinces. Fellowship training for MAA who work in Quebec or in other provinces was similar (68%). About one-third (33%) of UMA who work in Quebec obtained fellowship training. All alumni who received undergraduate education abroad (MAA n = 9; UMA n = 1) practice in Quebec. Three MAA and one UMA practice in the USA. Regression analysis suggests that working in Quebec is associated with obtaining an undergraduate medical education in that province (odds ratio 4.3; 95% confidence interval 1.1 to 21.2). CONCLUSIONS: The majority of MAA and UMA practice in Quebec, particularly if they received their undergraduate education there. Residents educated (undergraduate) in the rest of Canada are more likely to practice in other provinces. Residents with undergraduate education from abroad are highly likely to practice anesthesia in Quebec. A small portion of alumni elect to practice anesthesia in the USA. PMID- 22322663 TI - Effects of circadian disruption on mental and physical health. AB - Circadian (daily) rhythms in physiology and behavior are phylogenetically ancient and are present in almost all plants and animals. In mammals, these rhythms are generated by a master circadian clock in the suprachiasmatic nucleus of the hypothalamus, which in turn synchronizes "peripheral oscillators" throughout the brain and body in almost all cell types and organ systems. Although circadian rhythms are phylogenetically ancient, modern industrialized society and the ubiquity of electric lighting has resulted in a fundamental alteration in the relationship between an individual's endogenous circadian rhythmicity and the external environment. The ramifications of this desynchronization for mental and physical health are not fully understood, although numerous lines of evidence are emerging that link defects in circadian timing with negative health outcomes. This article explores the function of the circadian system, the effects of disrupted clocks on the brain and body, and how these effects impact mental and physical health. PMID- 22322664 TI - Mechanism and optimisation of the homoboroproline bifunctional catalytic asymmetric aldol reaction: Lewis acid tuning through in situ esterification. AB - The use of homoboroproline as a bifunctional catalyst in the asymmetric aldol reaction has been investigated mechanistically, particularly with respect to tuning the Lewis acidity of boron by in situ esterification with mildly sigma electron withdrawing diols such as hydrobenzoin and tartrate esters. The stability of simple cyclohexyl and cyclopentyl boronate diol esters shows that the 5-ring boronate esters are more stable, which sheds light on the mode of action of esterified homoboroproline catalyst in the enamine-mediated aldol reaction, which is also studied by NMR. The result is reaction optimisation to provide an efficient aldol reaction and a proposed mechanistic proposal. PMID- 22322665 TI - Bacopa monniera (L.) Wettst ameliorates behavioral alterations and oxidative markers in sodium valproate induced autism in rats. AB - Early prenatal or post natal exposure to environmental insults such as valproic acid (VPA), thalidomide and ethanol could induce behavioral alterations similar to autistic symptoms. Bacopa monniera, a renowned plant in ayurvedic medicine is useful in several neurological disorders. The purpose of the present study was to evaluate the effect of B. monniera on VPA induced autism. On 12.5 day of gestation the female pregnant rats were divided into control and VPA treated groups. They were administered saline/VPA (600 mg/kg, i.p.) respectively and allowed to raise their own litters. Group I-male pups of saline treated mothers. On postnatal day (PND) 21 VPA induced autistic male pups were divided into two groups (n = 6); Group II-received saline and Group III-received B. monniera (300 mg/kg/p.o.) from PND 21-35. Behavioral tests (nociception, locomotor activity, exploratory activity, anxiety and social behavior) were performed in both adolescence (PND 30-40) and adulthood (PND 90-110) period. At the end of behavioral testing animals were sacrificed, brain was isolated for biochemical estimations (serotonin, glutathione, catalase and nitric oxide) and histopathological examination. Induction of autism significantly affected normal behavior, increased oxidative stress and serotonin level, altered histoarchitecture of cerebellum (decreased number of purkinje cells, neuronal degeneration and chromatolysis) when compared with normal control group. Treatment with B. monniera significantly (p < 0.05) improved behavioral alterations, decreased oxidative stress markers and restored histoarchitecture of cerebellum. In conclusion, the present study suggests that B. monniera ameliorates the autistic symptoms possibly due to its anti-anxiety, antioxidant and neuro-protective activity. PMID- 22322666 TI - A multilevel examination of factors of the school environment and time spent in moderate to vigorous physical activity among a sample of secondary school students in grades 9-12 in Ontario, Canada. AB - OBJECTIVE: To examine associations between students' time spent in moderate to vigorous physical activity (MVPA) and the school built environment while also considering features of the schools' social environment and student-level characteristics. METHODS: Using surveys and GIS measures, multilevel linear regression analysis was applied to examine the environment- and student-level characteristics associated with time spent in MVPA among grade 9-12 students (n = 22,117) attending 76 secondary schools in Ontario, Canada as part of the SHAPES Ontario study. RESULTS: Statistically significant between-school random variation in student MVPA was identified [[Formula: see text] = 9,065.22 (250.64)]; school level differences accounted for 3.0% of the variability in student MVPA. Students attending a school that offered daily physical education or provided an alternate room for physical activity spent more time in MVPA than students attending a school without these resources. Moreover, as land-use mix diversity and walkability of the school neighbourhood increased, students' time spent in MVPA decreased. CONCLUSION: Developing a better understanding of the environment- and student-level characteristics associated with students' time spent in MVPA is critical for informing school-based physical activity intervention programmes and policies. PMID- 22322667 TI - Immune thrombocytopenia in patients with chronic lymphocytic leukemia is associated with stereotyped B-cell receptors. AB - PURPOSE: To assess biologic features related to the development of immune thrombocytopenia (ITP) in patients with chronic lymphocytic leukemia (CLL). EXPERIMENTAL DESIGN: We retrospectively analyzed 463 patients with CLL with available immunoglobulin heavy-chain variable (IGHV) gene status and B-cell receptor (BCR) configuration [heavy-chain complementary-determining region 3 (HCDR3)], of whom thirty-six developed ITP, according to previously defined criteria. Most of them had available cytogenetic analysis. RESULTS: We observed a significant association between ITP occurrence and IGHV unmutated gene status (P < 0.0001), unfavorable cytogenetic lesions (P = 0.005), and stereotyped HCDR3 (P = 0.006). The more frequent stereotyped HCDR3 subsets were #1 (IGHV1-5-7/IGHD6 19/IGHJ4; 16 of 16 unmutated) and #7 (IGHV1-69 or IGHV3-30/IGHD3-3/IGHJ6; 13 of 13 unmutated), both being significantly more represented among patients developing ITP (P = 0.003 and P = 0.001, respectively). Moreover, restricting the analysis to unmutated patients, subset #7 confirmed its independent significant association with the occurrence of ITP (P = 0.013). Both unmutated IGHV mutational status, del(11)(q23) and stereotyped BCR were significantly associated with shorter time to ITP development (P < 0.0001, P = 0.02, and P = 0.005, respectively) than other patients. CONCLUSION: Our data suggest that patients with CLL and peculiar BCR conformations are at higher risk of developing secondary ITP and that stereotyped BCR may be involved in the pathogenesis of this complication. PMID- 22322668 TI - Immune suppression in premalignant respiratory papillomas: enriched functional CD4+Foxp3+ regulatory T cells and PD-1/PD-L1/L2 expression. AB - PURPOSE: Respiratory papillomas, caused by human papillomaviruses types 6 and 11 (HPV6/11), are premalignant lesions with potential for malignant conversion. The cytokine and chemokine micromilieu of papillomas is T(H)2-like with a marked absence of IFN-gamma expression. To illuminate why patients with recurrent respiratory papillomatosis (RRP) fail to effectively control their disease, we further investigated the suppressive cellular microenvironment in papillomas. EXPERIMENTAL DESIGN: CD4(+)CD25(+)CD127(low/-)Foxp3(+) regulatory T cells (Treg) and CD4(+)CD25(-)CD127(low/-)Foxp3(-) T cells within papillomas were characterized and isolated. Their suppressor function was measured by inhibition of peripheral blood mononuclear cell (PBMC) proliferation. Expression of PD-1, CD69, and Helios was identified on these T cells. PD-L1, PD-L2, CCL17, and CCL22 mRNA was also identified in papillomas by quantitative PCR. RESULTS: Functional Tregs were markedly enriched in papillomas and strongly inhibited anti-CD3 and anti-CD28 antibody activated PBMC proliferation. The natural Treg marker Helios was reduced on Tregs from papillomas, indicating that the majority of Tregs in papillomas are adaptive. The majority of the papilloma-derived CD4(+) T cells expressed the CD4(+)CD25(-)CD127(low/-)Foxp3(-)PD1(+)CD69(+) phenotype and failed to suppress PBMC proliferation, suggesting that they are chronically activated and exhausted. The Treg-attracting chemokine CCL22 was equally expressed by all laryngeal tissues examined. However, CCL17 was robustly expressed by papillomas compared with unaffected laryngeal tissues from RRP patients and individuals without RRP. PD-L1 was elevated in papillomas compared with control laryngeal tissues. CONCLUSIONS: Papilloma CD4(+) T cells are enriched with functional Tregs, and the adaptive Helios(-) Treg fraction was increased within the T(H)2 like papilloma micromilieu. CD4(+)CD25(-)CD127(low/-)Foxp3(-) T-cells failed to suppress PBMC proliferation and may be exhausted. The PD-1/PDL-1 pathway may represent an additional immunosuppressive mechanism that contributes to defective HPV6/11 clearance in RRP. PMID- 22322669 TI - Characterization of gene amplification-driven SKP2 overexpression in myxofibrosarcoma: potential implications in tumor progression and therapeutics. AB - PURPOSE: Myxofibrosarcoma remains obscure in molecular determinants of clinical aggressiveness, for which we elucidated implications of SKP2 amplification. EXPERIMENTAL DESIGN: Array comparative genomic hybridization was applied on samples and cell lines (NMFH-1 to OH931) to search causal genes of tumor progression. SKP2 gene dosage was determined in 82 independent tumors for clinical correlates. Stable SKP2 knockdown was achieved in myxofibrosarcoma cells to assess its oncogenic attributes and candidate mediators in prometastatic function. Pharmacologic assays were evaluated in vitro and in vivo for the therapeutic relevance of bortezomib. RESULTS: DNA gains frequently involved 5p in which three amplicons were differentially overrepresented in samples behaving unfavorably, encompassing mRNA-upregulated TRIO, SKP2, and AMACR genes. Detected in NMFH-1 cells and 38% of tumors, SKP2 amplification was associated with SKP2 immunoexpression and adverse prognosticators and independently predictive of worse outcomes. Nevertheless, SKP2-expressing OH931 cells and 14% of such tumors lacked gene amplification. Knockdown of SKP2 suppressed proliferation, anchorage independent growth, migration, and invasion of sarcoma cells and downregulated motility-promoting genes, including ITGB2, ACTN1, IGF1, and ENAH. In vitro, bortezomib downregulated SKP2 expression at the mRNA level with p27(kip1) accumulation, induced caspase activation, and decreased cell viability in myxofibrosarcoma cells but not in fibroblasts. In vivo, bortezomib inhibited growth of NMFH-1 xenografts, the cells of which displayed decreased SKP2 expression but increased p27(kip1) and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL). CONCLUSIONS: As a predominant mechanism driving protein overexpression, SKP2 amplification confers tumor aggressiveness in myxofibrosarcoma. The sensitivity of myxofibrosarcoma cells to bortezomib with SKP2-repressing effect indicates the potentiality of ubiquitin-proteasome pathway as a therapeutic target. PMID- 22322670 TI - Serum autoantibody signature of ductal carcinoma in situ progression to invasive breast cancer. AB - PURPOSE: The identification of markers associated with progression to invasive breast cancer (IBC) is a major factor that can guide physicians in the initial therapeutic decision and the management of ductal carcinoma in situ (DCIS). EXPERIMENTAL DESIGN: We examined autoantibody targets in 20 DCIS and 20 IBC patients using protein microarrays and identified humoral responses that can be used to distinguish the two groups. The five most differentially targeted antigens were selected to generate an autoantibody signature for the in situ to invasive breast cancer transition. This signature was next tested on 120 independent samples (61 DCIS and 59 IBC) using specific ELISA assays. The prognosis value of the autoantibody signature was finally evaluated in a cohort of DCIS patients followed for 5 years. RESULTS: A set of five autoantibody targets (RBP-Jkappa, HMGN1, PSRC1, CIRBP, and ECHDC1) with the highest differential signal intensity found in the protein microarrays experiment was used to establish an autoantibody signature of the DCIS to IBC transition. Using ELISA, this signature significantly discriminated DCIS from IBC [area under the ROC curve (AUC) = 0.794, 95% confidence interval (CI): 0.674-0.877]. Interestingly, our panel could highly distinguish low-grade DCIS from high-grade DCIS exhibiting an AUC of 0.749 (95% CI: 0.581-0.866). Finally, using a Kaplan Meier analysis, the autoantibody signature could significantly divide the DCIS patients into a poor prognosis group and a good prognosis group (P = 0.01). CONCLUSION: These results indicate the potential of autoantibody detection as a new prognostic test with possible clinical implications for the management of DCIS. PMID- 22322671 TI - ESR1 amplification in breast cancer: controversy resolved? AB - The determination of oestrogen receptor alpha (ERalpha) expression in breast cancers has been for many years the standard of care for guiding patient management. In 2007, Holst and colleagues published the previously unappreciated observation that the ERalpha gene, ESR1, was amplified in 21% of breast cancers, and that ESR1 gene amplification identified those individuals with high ERalpha expression in their tumours and who were likely to respond to hormonal manipulation. This has been a controversial area. Others have tried to reproduce these findings but the results have been mixed with respect to amplification frequency, and even contradictory with respect to prognostic and predictive value. The controversy may have now been resolved. Ooi et al, in this issue of the journal, show that the large clustered FISH signals that have been interpreted as ESR1 amplification are sensitive to RNase treatment, indicating that FISH is detecting accumulation of ESR1 transcripts in the nucleus of breast cancer cells expressing high levels of ERalpha, rather than gene amplification events. This story has important lessons for translational cancer research, and in particular FISH studies of gene copy number. PMID- 22322672 TI - A shared MHC supertype motif emerges by convergent evolution in macaques and mice, but is totally absent in human MHC molecules. AB - The SIV-infected rhesus macaque (Macaca mulatta) is the most established model of AIDS disease systems, providing insight into pathogenesis and a model system for testing novel vaccines. The understanding of cellular immune responses based on the identification and study of Major Histocompatibility Complex (MHC) molecules, including their MHC:peptide-binding motif, provides valuable information to decipher outcomes of infection and vaccine efficacy. Detailed characterization of Mamu-B*039:01, a common allele expressed in Chinese rhesus macaques, revealed a unique MHC:peptide-binding preference consisting of glycine at the second position. Peptides containing a glycine at the second position were shown to be antigenic from animals positive for Mamu-B*039:01. A similar motif was previously described for the D(d) mouse MHC allele, but for none of the human HLA molecules for which a motif is known. Further investigation showed that one additional macaque allele, present in Indian rhesus macaques, Mamu-B*052:01, shares this same motif. These "G2" alleles were associated with the presence of specific residues in their B pocket. This pocket structure was found in 6% of macaque sequences but none of 950 human HLA class I alleles. Evolutionary studies using the "G2" alleles points to common ancestry for the macaque sequences, while convergent evolution is suggested when murine and macaque sequences are considered. This is the first detailed characterization of the pocket residues yielding this specific motif in nonhuman primates and mice, revealing a new supertype motif not present in humans. PMID- 22322673 TI - Nomenclature and listing of celiac disease relevant gluten T-cell epitopes restricted by HLA-DQ molecules. AB - Celiac disease is caused by an abnormal intestinal T-cell response to gluten proteins of wheat, barley and rye. Over the last few years, a number of gluten T cell epitopes restricted by celiac disease associated HLA-DQ molecules have been characterized. In this work, we give an overview of these epitopes and suggest a comprehensive, new nomenclature. PMID- 22322674 TI - Highly divergent dimorphic alleles of the proteasome subunit beta type-8 (PSMB8) gene of the bichir Polypterus senegalus: implication for evolution of the PSMB8 gene of jawed vertebrates. AB - The proteasome subunit beta type-8 (PSMB8) gene encodes a catalytic subunit of the immunoproteasome, which is involved in the generation of peptides presented by MHC class I molecules. To date, highly diverged dichotomous alleles of PSMB8 have been reported in Oryzias species (actinopterygian teleosts) and Xenopus species (sarcopterygian amphibians). These dimorphic alleles share a similar substitution (A/V(31)F/Y) at the 31st position of the mature protein, which is most probably involved in formation of the S1 pocket. This substitution likely confers different cleavage specificities on the dimorphic PSMB8s. In addition, two paralogous PSMB8 genes possessing the A and F residues at the 31st position have been reported in sharks. Phylogenetic analysis indicated that the two types of PSMB8 of Oryzias, Xenopus, and sharks arose by independent evolutionary events. Here, we identified another pair of dimorphic alleles of PSMB8, which have the A and F residues at the 31st position of the mature protein, from bichir, Polypterus senegalus, a basal actinopterygian. The sequences of the mature proteins-encoding region of the dimorphic alleles of bichir PSMB8, the A and F types, showed only 72.7% and 77.5% identities at the nucleotide and the deduced amino acid levels, respectively. Their intronic sequences show almost no similarity, indicating that the dimorphic alleles of bichir PSMB8 have a very ancient origin. However, phylogenetic analysis showed that the dimorphisms of PSMB8 of bichir, Xenopus, and Oryzias arose by independent evolutionary events, suggesting the presence of a strong selective pressure for possessing the dimorphism. PMID- 22322676 TI - [Evolution, emotion, language and conscience in the postrationalist psychotherapy]. AB - A complex system process oriented approach, in other words a constructivistic postrationalist cognitive one to psychology and to psychopathology, stresses the close interdependency among processes as evolution, emotion, language and conscience. During evolution, emotions, whose biological roots we share with superior primates, should be specialized and refined. Along this process should become necessary a more and more abstract way of scaffolding the enormous quantity of data a brain could manage. Cognitive abilities, rooted in the emotional quality of experience, allow - during the phylogenetic development - more and more complex patterns of reflexivity until to the necessary ability of recognizing other's intention and consequently of lying. Language, abstract ability usefull to give increasing experiential data scaffolding, probably coming from motor skills development, brings at the same time the possibility, for a human knowing system, of self-consciousness: to do this it's owed to detach from itself, that is experience a deep sense of loneliness. Here it is that the progressive cognitive skills development is linked to the possibility of lying and of self-deception as long as the acquiring of advanced levels of selfconsciousness. PMID- 22322675 TI - IL1RN genetic variations and risk of IPF: a meta-analysis and mRNA expression study. AB - Idiopathic pulmonary fibrosis (IPF) is a rare and devastating lung disease of unknown aetiology. Genetic variations in the IL1RN gene, encoding the interleukin 1 receptor antagonist (IL-1Ra), have been associated with IPF susceptibility. Several studies investigated the variable number tandem repeat (VNTR) or single nucleotide polymorphisms rs408392, rs419598 and rs2637988, with variable results. The aim of this study was to elucidate the influence of polymorphisms in IL1RN on IPF susceptibility and mRNA expression. We performed a meta-analysis of the five case-control studies that investigated an IL1RN polymorphism in IPF in a Caucasian population. In addition, we investigated whether IL1RN mRNA expression was influenced by IL1RN polymorphisms. The VNTR, rs408392 and rs419598 were in tight linkage disequilibrium, with D' > 0.99. Furthermore, rs2637988 was in linkage disequilibrium with the VNTR (D' = 0.90). A haploblock of VNTR*2 and the minor alleles of rs408392and rs419598 was constructed. Meta-analysis revealed that this VNTR*2 haploblock is associated with IPF susceptibility both with an allelic model (odds ratio = 1.42, p = 0.002) and a carriership model (odds ratio = 1.60, p = 0.002). IL1RN mRNA expression was significantly influenced by rs2637988, with lower levels found in carriers of the (minor) GG genotype (p < 0.001). From this meta-analysis, we conclude that the VNTR*2 haploblock is associated with susceptibility to IPF. In addition, polymorphisms in IL1RN influence IL-1Ra mRNA expression, suggesting that lower levels of IL-1Ra predispose to developing IPF. Together these findings demonstrate that the cytokine IL-1Ra plays a role in IPF pathogenesis. PMID- 22322677 TI - The emergence of mind and emotion in the evolution of neocortex. AB - The most deeply transformative concept for the growth of 21st Century psychiatry is the constellation of the chaotic dynamics of the brain. Brains are no longer seen as rational systems that are plagued with emotional disorders reflecting primitives inherited from our animal ancestors. Brains are dynamical systems that continually create patterns by acting intentionally into the environment and shaping themselves in accord with the sensory consequences of their intended actions. Emotions are now seen not as reversions to animal behaviors but as the sources of force and energy that brains require for the actions they take to understand the world and themselves. Humans are unique in experiencing consciousness of their own actions, which they experience as conscience: guilt, shame, pride and joy. Chaotic brain dynamics strives always for unity and harmony, but as a necessary condition for adaptation to a changing world, it repeatedly lapses into disorder. The successes are seen in the normal unity of consciousness; the failures are seen in the disorders that we rightly label the schizophrenias and the less severe character disorders. The foundation for healthy unity is revealed by studies in the evolution of brains, in particular the way in which neocortex of mammals emerged from the primitive allocortex of reptiles. The amazing facts of brain dynamics are now falling into several places. The power-law connectivity of cortex supports the scale-free dynamics of the global workspace in brains ranging from mouse to whale. That dynamics in humans holds the secrets of speech and symbol utilization. By recursive interactions in vast areas of human neocortex the scale-free connectivity supports our unified consciousness. Here in this dynamics are to be sought the keys to understanding and treating the disorders that uniquely plague the human mind. PMID- 22322678 TI - An evolutionary perspective for contemporary psychiatric research. AB - Behaviour represents the ultimate output of the brain and is characterized by a high level of inter-individual variability. On the one hand, taking into account evolutionary history and adaptive significance of behavioural responses allows to design experimental protocols that improve both data quality and interpretation. On the other hand, a multilevel approach, which analyses factors ranging from the genetic set up to the socioeconomic status, leads to a more comprehensive and effective investigation of mechanisms underlying brain function. Exploitation of this approach in clinical studies may provide new strategies to more precisely investigate psychiatric disorders. PMID- 22322679 TI - [A postrationalist approach to emotional reciprocity in psychotherapy]. AB - In a postrationalist approach to cognitive psychotherapy the therapeutic relationship becomes a tool for exploring, by which, the patient manages to understand the rules which govern the rigid logical processes of his own personal meaning organization. A more accurate knowledge of one's own attitudes is the crucial variable that lets the patient assimilate problematic experiences. The therapist role assume the form of a "strategical oriented emotive disturber" who is extremely careful to utilize the emotional swings that he live in reciprocity with the patient, and who is aware of is own, as it is his emotions which modulate the patient's perceptions and understanding of problems. PMID- 22322680 TI - [The reciprocity rule in the construction of relationships as the key in relational processes]. AB - Reciprocity as an expression of the therapist-patient relationship is pointed-out by Mario Reda who refers to Comparetti's studies on the mother-foetus reciprocity, mediated by the so-called "jumps". Reciprocal behaviours are clearly observable during bird and other animal courtship behaviour, whereas in the Sapiens sapiens species, we may observe the establishing of a very complex reciprocity system, which starts with gestures and bodily attitudes, subsequently activating sensory-motor emotional schemata and internal working models, thus enabling the construction of personal meanings. A relationship may result from an encounter provided that "compatible" meanings are constructed in the context of "possible reciprocity" of significant systems. The observation of reciprocity provides a concrete possibility to reduce the risk of absolute subjectivity related to the I or the you, superceding it through the us. PMID- 22322681 TI - Restraint eating and sensitivity to stress: preliminary experimental evidence. AB - BACKGROUND: Restrained eaters (RE) typically display a recurrent pattern of restraint/overeating. This fluctuating behavior has recently been connected to mood and the affective style in general. In this context, it is argued that RE may be sensitive to stress. Nevertheless, there is no substantial evidence demonstrating that RE present behavioral or psychophysiological patterns that indicate this sensitivity. AIM: To test whether there is a differential modulation of punishment in RE behavior within an experimental paradigm that manipulates the reward/punishment contingency. METHOD: 104 female university students (31 RE and 73 controls) carried out an experimental task in which, under different reward/punishment contingencies, they had to choose an advantageous option. RESULTS: A significant interaction was observed between the Choice and the Group, revealing that the frequency of punishment inhibits the choice response in RE, independent of its advantage/disadvantage. Although complementary studies are required, the data represent preliminary evidence that RE are sensitive to stress. The clinical implications of these findings are discussed. PMID- 22322682 TI - [Linguistic evolution and creation in psychotherapy]. AB - AIM: Clarify how linguistic coevolution and creation are crucial in the theory of psychotherapeutic technique. METHOD: The paradox of private language, structural coupling and synchronization theory, are introduced in order to highlight how multiple components are involved in psychotherapeutic relations. A review and discussion of some relevant studies. RESULTS: A therapeutic approach based on coevolution, bipersonal fields, implicit communication and procedural knowledge can be more effective in modifying different forms of memory. DISCUSSION: This evidence based approach represents a scientific advancement in psychotherapy, including effectiveness of care, personalisation and ethics. PMID- 22322683 TI - [Subjectivity sense, language and subject: a new postrationalist perspective in psychotherapy]. AB - This paper discusses the philosophical roots of the concept of sense in Russian philosophy and linguistic, analyzing its consequences for the social sciences, in particular for psychology. Starting from the relevance of the Vygotsky's definition of sense, through which that concept became psychological, is discussed its relevance for advancing forward in a proposal about subjectivity from a cultural historical approach. Advancing on this proposal, the concept of subjective sense is defined as a subjective unity whose focus, rather than being on the unity between word and psychological elements, as Vygotsky stated, is on the unity between symbolical processes and emotions. This theoretical account leads to a different representation of the relation between language, subject and subjectivity, which support a non rationalistic reductionism concerning subjectivity. Finally, on the basis of this non individualistic and non essentialist definition of subjectivity are discussed some of its implications for the development of a non rationalistic approach in psychotherapy. PMID- 22322684 TI - [Couples counseling with Latinos]. AB - Intimate ties and emotional relationship gain the function to confirm, to stabilize and, afterwards, to structure the coherency's model of the structured self-organization up to that moment. When the couple perceives the bond of the relationship such as a sole and exclusive for a person, they take a leading role to be able to deduce a sense of individuality and uniqueness in the way to feel himself in the world. Based on these considerations, in this paper I propose a brief description of a counselling method, which characterises the work I am carrying out since several years in the counselling and therapy with couples. PMID- 22322685 TI - [Change of personal meaning: perspectives of a research program in psychotherapy process]. AB - This paper describes the development of a research program in psychotherapy whose main objective is to understand and modify the personal meaning in different mental health problems. We describe the Psychological Distress Reconstruction Pattern (revised) which has proved been useful to guide the therapist in understanding and modificating the dysfunctional meaning in clinical conditions. PMID- 22322686 TI - [Psychotherapeutic postrationalist approach to psychosis]. AB - The article describes the heuristic contributions of the postrationalist psychosis model. It highlights the difference with other psychotherapeutic interventions in psychosis (phenomenological, psychoanalytic, cognitive) due to a change in epistemological perspective, in particular the distinction of domains, that of the observer and the observed, and the reconstruction of the subjective path that organizes a psychotic subject. The psychotherapy aims to contextualize the experience through the sequencing of the narrative to get an internalization of these experiences, lived in the crisis as external and alien to the self. PMID- 22322687 TI - [Tacit metarepresentation and affective sense of personal identity. An approach to understanding severe psychiatric disorders of adolescence and young adulthood]. AB - The results of present-day research in the field of "Dissociation Paradigm", regarding the capacity of the human mind to perceive, learn, and store information that in appearance passes as unnoticed, support the constructivist hypothesis of the active, selective and constructive condition of consciousness, in addition to the existence of a tacit dimension of knowledge that operates in functional relationship with the former. Unconscious mental states are intrinsically intentional. This is to say that they imply a semantic or cognitive connotation that is capable of affecting phenomenical experience and therefore behavior. In addition, the precocious existence of a tacit metarepresentational system in normally developed children has been proven, which is essential for guaranteeing the deployment of the process of functional coevolution between affectivity and consciousness, by which the experience of personal identity is acquired. These discoveries allow the inference of a "tacit affective metarepresentational recurrence", the organizational foundation on which a unified, sustainable, and continuous sense of the experience of personal identity is structured, and also allow us to hypothesize a "tacit metarepresentational mourning", a specific type of grief which is the chief foundation of the majority of psychopathological disorders. This concept may represent a potential explanation of the severe mental disorders of adolescence and young adulthood. The hypothesis of the present work is that, in the ambiguous context of Postmodern Culture, the prolongation of the adolescent period, facilitated by the welfare state, hinders the dealing with the aforementioned mourning, leading to an increment of depressive states and suicidal behavior among young people. PMID- 22322688 TI - [Explicative psychopathology in obsessive-compulsive disorder: a postrationalist viewpoint]. AB - While descriptive psychopathology of obsessive-compulsive disorder (OCD) is now well-established, there is still a lack of a satisfying model of explicative psychopathology that explains the mechanisms that generate obsessive phenomenology. The main attempts to delineate such a model are based on cognitive therapy: according to this approach OCD is a consequence of dysfunctional beliefs (i.e. overestimation of the risk or of the influence of one's own mind on the reality). On the contrary, according to postrationalist cognitive approach, OCD would be based on a characteristic personality structure, which could be identified not only in patients with OCD but also in those who will never develop symptoms. In symptomatic individuals this organization ("Obsessive" Personal Meaning Organization) is more rigidly structured. In particular, there is crystallization of so-called diachronic attitude, which is the key to explain most of the symptoms. PMID- 22322689 TI - [The case of Giorgia: a systemic cognitive postrationalist intervention]. AB - To describe and to explain a clinical case from a cognitive systemic perspective means to focus on "how" the different data were set in order and organized during the therapy. The theoretical and clinical experience that uses this approach is based upon the integration of two conceptual models: the cognitive postrationalist one and the relational systemic one. These two approaches are founded upon the concept of system. The first one addresses the internal dimension, focusing on something that is not directly observable, taking into account the development processes and the maintenance of identity, that is to say the self organization of personal meaning. On the other hand, the second approach considers the structure of relations, its path and boundary, focusing on the mode of communication. The cognitive systemic model springs out of the integration of these two different ways of observing our object of investigation, intending to better the knowledge of the individual and of its context. The essay describes a clinical case study along a processual systemic method, in every phase, beginning with the intervention on the individual's system, subsequently engaging the family's system and all the sub systems that are part of the subjective experience. PMID- 22322690 TI - Reconstructing meaning in bereavement. AB - Bereavement, in the form of the loss of a significant attachment figure to death, disrupts the self-narratives of survivors, and typically launches them into an unsought quest for meaning in the loss as well as in their changed lives. A growing body of research on diverse groups - bereaved parents, young people, elders - suffering loss through both natural and violent death, documents the link between inability to find meaning in the experience and the intensity of complicated grief they suffer. This article reviews this literature, arguing that processes of sense-making and benefit-finding play a crucial role in bereavement adaptation for many of the bereaved, and accordingly that interventions that facilitate processes of meaning reconstruction can support effective psychotherapy for those struggling with intense and prolonged grief. PMID- 22322691 TI - Production of chiral alcohols from prochiral ketones by microalgal photo biocatalytic asymmetric reduction reaction. AB - Microalgal photo-biocatalysis is a green technique for asymmetric synthesis. Asymmetric reduction of nonnatural prochiral ketones to produce chiral alcohols by microalgal photo-biocatalysis was studied in this work. Acetophenone (ACP) and ethyl acetoacetate (EAA) were chosen as model substrates for aromatic ketones and beta-ketoesters, respectively. Two prokaryotic cyanophyta and two eukaryotic chlorophyta were selected as photo-biocatalysts. The results proved that nonnatural prochiral ketones can be reduced by microalgal photo-biocatalysis with high enantioselectivity. Illumination is indispensable to the photo-biocatalysis. For aromatic ketone, cyanophyta are eligible biocatalysts. For ACP asymmetric reduction reaction, about 45% yield and 97% e.e. can be achieved by the photo biocatalysis reaction with Spirulina platensis as biocatalyst. On the contrary, chlorophyta are efficient biocatalysts for beta-ketoester asymmetric reduction reaction among the four tested algae. For EAA asymmetric reduction reaction, about 70% yield and 90% e.e. can be achieved with Scenedesmus obliquus as biocatalyst. The microalgae used in this study outperformed other characterized biocatalysts such as microbial and plant cells. PMID- 22322692 TI - In-plane pyridinium cation reorientation in bis-thiourea chloride, bromide and iodide: quasielastic neutron scattering combined with molecular dynamics simulations. AB - We have studied the dynamics of bis-thiourea pyridinium chloride and bromide by means of quasielastic neutron scattering (QENS). The QENS data allow describing the geometry of the in-plane motion of the pyridinium cation and reveal that it is similar to the motion previously observed in bis-thiourea pyridinium iodide. Molecular dynamics (MD) simulations have been performed to investigate the cation dynamics on the high temperature phase of the full series of compounds: bis thiourea pyridinium chloride, bromide and iodide. Three different models of intermolecular potential have been tested and the agreement between the simulated and experimental elastic incoherent structure factors (EISFs) is used to select the more realistic one. The detailed analysis of the MD results indicates that Coulombic interactions together with the formation of hydrogen bonds between the pyridinium cation and the host sublattice influence strongly the geometry of the in-plane cation reorientation. PMID- 22322725 TI - Aspirin enhances doxorubicin-induced apoptosis and reduces tumor growth in human hepatocellular carcinoma cells in vitro and in vivo. AB - Combined therapy with multiple drugs is a common practice in the treatment of cancer, which can achieve better therapeutic effects than a single drug, and can reduce the side effects as well as drug resistance. This study aimed to determine whether aspirin (ASA) shows synergism with doxorubicin (DOX) in HepG2 human hepatocellular carcinoma cells in vitro and in a HepG2 cell xenograft model in BALB/c nude mice. When treated in combination, DOX (0.25 nmol/ml) and ASA (5 umol/ml) produced strong synergy in growth inhibition, cell cycle arrest and importantly, apoptosis in vitro in comparison to single treatments. Moreover, ASA (100 mg/kg/day orally) and DOX (1.2 mg/kg biweekly ip) induced synergistic antitumor activity in the HepG2 cell xenograft model in nude mice. Therefore, the combination of ASA and DOX could be used as a novel combination regimen which provides a strong anticancer synergy in the treatment of hepatocellular carcinoma. PMID- 22322726 TI - Utility of frozen section in assessment of margins and neck node metastases in patients undergoing surgery for carcinoma of the tongue. AB - OBJECTIVE: The aims of this study are to evaluate the impact of frozen section in achieving adequate surgical margin and to study the accuracy of frozen section in detection of occult metastases. MATERIALS AND METHODS: This was a retrospective review of prospectively collected data of 877 patients with squamous cell carcinoma of the tongue who underwent surgery and intra-operative frozen section at our center from January 2007 to June 2010. RESULTS: Frozen section was found to have very high accuracy in assessment of margin as well nodal status. On frozen section, 2% of our patients had positive margins and 21% had close margins. Most of these underwent intra-operative revision and at final pathology, 1.2% patients had positive margins and 11% were close. Of the 651 supraomohyoid neck dissections performed, one third were found to have occult metastases on frozen section. Of those reported positive on frozen section, 68% got additional removal of level 4 +/- 5. Interestingly, 11% of these additionally removed nodes harbored metastases at final pathology. However, 7% of the patients were wrongly declared negative on frozen section. Tumor thickness was predictor of margin positivity as well as occult metastases. Tumor volume did not correlate with occult metastases or margin status. CONCLUSIONS: Frozen section nearly halves the rates of positive margin and close margins which certainly translates into clinical benefits. The incidence of 11% positive nodes in the frozen section guided removal of lower levels is an important finding in our study that questions the ability of supraomohyoid neck dissection to completely eradicate the nodal burden in such patients. PMID- 22322727 TI - Metronomic chemotherapy in advanced oral cancers. AB - CONTEXT: To assess the feasibility of metronomic chemotherapy in the palliative care setting. AIMS: To study the toxicity profile and efficacy of metronomic chemotherapy for palliation in oral cavity cancers. SETTINGS AND DESIGN: Retrospective analysis of prospectively collected data. MATERIALS AND METHODS: Subjects receiving metronomic chemotherapy from August 2010 to January 2011 for palliation in oral cancers subjected to certain criteria were included. Metronomic chemotherapy offered was a combination of twice daily celecoxib 200 mg and weekly methotrexate 15 mg/m 2 .The chemotherapy was continued till disease progression, intolerable side effects or patients' desire to stop. The toxicity profile was reported in accordance with common terminology criteria for adverse events (CTCAE) version 4.02. The efficacy was noted in terms of symptom control, response rates, progression free survival (PFS) and overall survival (OS). STATISTICAL ANALYSIS USED: SPSS version 16 has been utilized. Descriptive analysis has been presented. The Kaplan-Meier survival analysis was performed for estimation of the PFS and OS. RESULTS: Eighteen patients with a median age of 50.5 years, 13 males and 5 females, participated in the study. Five patients had received no previous treatment while the rest had some form of previous treatment. ECOG performance status was 1 in 14 patients and 2 in 4 patients. Grade 3-4 mucositis was seen in one patient. Clinical benefit rate was 66.67%. The estimated median PFS and median OS were 5.2 months and not reached respectively. CONCLUSIONS: Use of metronomic chemotherapy seems promising and well tolerated in this setting. Large trials are warranted to confirm these results. PMID- 22322728 TI - Minor salivary gland tumors of the oral cavity: a case series with review of literature. AB - BACKGROUND: Minor salivary gland tumors (MSGTs) are unusual, accounting for only 15-20% of all salivary gland tumors. The commonest site of MSGTs of the head and neck is oral cavity. AIMS: To describe our experience with MSGTs of oral cavity seen over a period of one decade and elucidate their prognostic factors. MATERIALS AND METHODS: Over a period of 10 years, from 1991 to 2000, all MSGTs of oral cavity were analyzed. All demographic, treatment and survival data were recorded. Kaplan-Meier curves were used to find the survival. Multivariate analysis was performed using Cox regression. RESULTS: We treated 104 patients with curative intent. The commonest site was hard palate, accounting for 54.8% of all sites. The commonest histology was adenoid cystic carcinoma (45.2%). There were 17 (16.34%) pleomorphic adenoma cases, while the remaining 87 (83.66%) were minor salivary gland malignancies. Treatment was surgical in 91.3% of patients. Adjuvant radiotherapy was administered in 38.5% of patients. The median follow-up was 50 months. Recurrences were seen in 22 (25.3%) of the 87 malignant cases. Using Kaplan-Meier analysis, the expected 10-year overall and disease-free survivals were 75.2 and 65.8%, respectively. Survivals were better in non-adenoid cystic tumors (non-ACC). On multivariate analysis, T status, tumor grade and adjuvant therapy were independent prognostic factors for disease-free survival. CONCLUSIONS: MSGTs of oral cavity have good overall survival despite recurrences. T stage, adjuvant radiotherapy and grade are independent prognostic factors for disease-free survival. Adenoid cystic tumors have worse outlook than non-ACC. PMID- 22322729 TI - Serum circulating immune complexes as prognostic indicators in premalignant and malignant lesions of oral cavity during and following radiotherapy. AB - AIM: The aim of the study has been to quantitatively estimate and compare the circulating immune complexes (CIC) in pre-malignant and malignant lesions of oral cavity and to serially monitor the CIC levels in oral squamous cell carcinoma (SCC) during / following radiotherapy as to assess the status of the disease and to understand the prognostic significance. MATERIALS AND METHODS: The present study was carried out on 90 individuals divided into three groups and CIC was estimated by spectrophotometric method using polyethylene glycol (PEG) precipitation method. The mean CIC level was determined in each group and was correlated with the degree of differentiation and degree of dysplasia in malignant and pre-malignant group respectively. The effect of radiotherapy on the level of CIC was studied after 2400 rad and after one week of 4500 - 5000 rad. RESULTS: It was observed that the mean CIC level in the control group was significantly lower (59.56 +/- 8.11) when compared with the pre-malignant group (75.93 +/- 12.89) and malignant group (92.66 +/- 13.96). Among the pre-malignant group, leukoplakia had the highest mean CIC level followed by lichen planus and oral submucous fibrosis (OSMF), suggesting its greater malignant potential. No correlation could be established between degree of differentiation and degree of dysplasia with the CIC levels in malignant and premalignant groups respectively. There was a definite decrease in the mean CIC levels in patients undergoing radiotherapy. CONCLUSION: The pretreatment value of CIC can be used as a prognostic indicator. A high CIC level would probably indicate a poor prognosis. PMID- 22322730 TI - Salivary lactate dehydrogenase levels in oral leukoplakia and oral squamous cell carcinoma: a biochemical and clinicopathological study. AB - BACKGROUND: Oral cancer is the third most common form of malignancies in India. In many cases it develops at the site of premalignant lesion. Transformation of normal tissue to premalignant lesion and further to oral cancer results in alteration in glycolytic pathway and hence the lactate dehydrogenase levels. Therefore, a study was carried out to determine the changes in the salivary alterations in lactate dehydrogenase (LD) levels oral leukoplakia (OL) and oral cancer (OC). METHODS: Seventy-five patients reporting to department of oral medicine and radiology, were enrolled into the study which includes 25 patients each of oral leukoplakia, 25 of oral cancer and 25 healthy controls (HC). Unstimulated whole saliva measuring 1 mL will be collected from each of these patients by spit method in centrifuged and evaluated for LDH levels using the standard kit method. The data obtained were subjected to statistical analysis using the SPSS software version 17. RESULTS: The mean salivary lactate dehydrogenase levels were higher in males in comparison to females in all three study groups OL, OC and HC. The salivary lactate dehydrogenase levels in the controls group, oral leukoplakia group and oral cancer were 79.50 +/- 4.67 IU/L, 136.46 +/- 3.36 IU/L and 148.77 +/- 4.83 IU/L, respectively. There was a significant difference in the mean salivary levels of the above groups. CONCLUSION: Salivary lactate dehydrogenase levels are consistently higher in oral precancer and cancer hence it could be future marker. PMID- 22322731 TI - Raman spectroscopy in head and neck cancers: toward oncological applications. AB - AIMS: To test the spectral reproducibility of earlier findings under ex vivo conditions and to record good quality in vivo spectra in clinically implementable time in finger print region. MATERIALS AND METHODS: Spectra from 20 ex vivo tissues (10 normal and 10 tumor) were recorded using fiber optic probe coupled Raman spectrometer. In vivo spectra from 10 healthy volunteers were also recorded. Spectral differences were analyzed by PC-LDA method followed by validation by leave-one-out and test samples. RESULTS: Spectral features of ex vivo normal tissue suggest predominant lipid features while protein is high in tumor conditions. Major spectral features of in vivo healthy volunteers share several commonalities with ex vivo normal tissues except minor differences in amide III region. Classification efficiency of 90, 85 and 96% for ex vivo tumor, normal and in vivo normal standard models, respectively after leave-one-out cross validation, was observed. Test prediction efficiency of standard models of ex vivo normal, ex vivo tumor and in vivo healthy volunteers were 82.5, 92.5 and 100%, respectively. CONCLUSIONS: Our findings corroborate with the reported ex vivo and in vivo normal spectral features. Features of in vivo Raman spectra show strong similarities with ex vivo normal spectra minor but significant differences were also observed. Findings of this study indicate that with our instrument in vivo Raman spectra in finger print region can be recorded in short and clinically implementable time. PMID- 22322732 TI - The first special issue.... of many more to come! PMID- 22322733 TI - Effective strategies for oral cancer control in India. PMID- 22322734 TI - Oral cancer: Premalignant conditions and screening--an update. AB - Oral cancers form a significant portion of the cancer burden seen in our country. Typically, they tend to be preceded by a premalignant state for a long time. This article discusses the various types of premalignant disorders commonly seen in daily practice. Also, it is important to screen patients for these conditions so as to detect malignant changes early. Previously, the screening of patients for oral cancer and precancerous lesions has relied mainly on conventional oral examination. Nowadays, many newer techniques are available to potentially assist in the screening of healthy patients for evidence of oral cancer. This article attempts to review the current literature for screening methods and adjuncts such as toluidine blue, brush cytology, tissue chemiluminescence and autofluorescence. PMID- 22322735 TI - The role of intensity modulated radiotherapy in advanced oral cavity carcinoma. AB - It is increasingly being recognized that oral cavity cancer incidences are rising globally. Furthermore, these tumors represent a high risk group of tumors comparative to other head and neck tumor sub-sites and have a high preponderance of occult nodal metastases. Surgery alone leads to excellent outcomes in early stage disease. Advanced tumors require adjuvant radiotherapy with or without concomitant chemotherapy. Irradiation using 3D conformal radiotherapy results in high incidence of late radiation side-effects. Xersostomia and mandibular osteoradionecrosis result in most significant effects on patients' quality of life. Intensity modulated radiotherapy (IMRT) is an advanced approach to 3-D treatment planning and conformal therapy (3D-CRT). It optimizes the delivery of irradiation to irregularly-shaped volumes and has the ability to produce concavities in radiation treatment volumes and hence enables sparing of normal tissue while delivering adequate doses to the tumor volumes. In this manuscript, we discuss the advantages of IMRT based on review of published peer reviewed literature. PMID- 22322736 TI - Toxicity with radiotherapy for oral cancers and its management: a practical approach. AB - Radiotherapy-induced damage in the oral mucosa is the result of the deleterious effects of radiation, not only on the oral mucosa itself but also on the skin, adjacent salivary glands, bone, dentition, and masticatory apparatus. From basic skin care to dental and oral health maintenance, several ointments and lotions, oral and parenteral medications, biological response modifiers, cytoprotective drugs, newer radiation techniques and surgery have been introduced to combat and more importantly to prevent the development of these complications. Radiotherapy induced oral complications involve complex and dynamic pathobiological processes. This in the immediate- and long-term course lowers the quality of life and predisposes patients to serious clinical disorders. Here, we focus on these oral complications of radiotherapy, highlight preventive and therapeutic developments, and review the current treatment options available for these disorders. PMID- 22322737 TI - Dental implants in irradiated jaws: a literature review. AB - Surgical treatment of head and neck cancer frequently results in defects that challenge conventional prosthetic rehabilitation. Successful rehabilitation using tissue supported dentures in such cases has been reported to be less than 20%. With the loss of jaw bones and thus the support, there is loss of retention to a great deal. Also, teeth loss on the side of the defect adds to failure in retention. Scar tissue formation, deviation of jaw due to muscle pull, decreased mouth opening, loss of sulcus and non vertical force are some of the common adversaries of jaw resection especially mandibular resection which pose great limitation on the stability and success of prospective prosthetic rehabilitation. The advent and application of biologically acceptable implants in clinical dentistry has contributed to restoring the defects of the deficient maxillofacial systems. Surgical intervention in patients who had received head and neck irradiation is preferably avoided as it has been associated with decreased healing and increased potential for development of osteoradionecrosis. Hence an implant as an option when surgical field has received tumerocidal radiation is empirically excluded. The purpose of this article is to review the studies and reports published in various journals related to osseointegrated implant rehabilitation in irradiated bones. PMID- 22322738 TI - Prospective analysis of reasons for non-enrollment in a phase III randomized controlled trial. AB - AIM: This study aims to provide information on the accrual rate and to identify the reasons for non-enrollment of oral cancer patients into a clinical trial. SETTING AND DESIGN: Prospective study conducted at the Tertiary Cancer Centre (India). MATERIALS AND METHODS: Patients eligible and screened for the oral cancer adjuvant therapy (OCAT) were logged prospectively and reasons for non enrollment were documented which were broadly divided into patient and trial related. STATISTICAL ANALYSIS USED: Demographic characteristics of the non enrolees were compared with the enrolled. Factors predicting non-enrollment were analyzed using multivariate logistic regression test. RESULTS: A total of 1335 patients with locally advanced cancer of the oral cavity were screened of whom 498 (37%) could be enrolled. Among non enrolled 837 patients, 182 (22%) had the trial-related reasons and 655 (78%) had patient-related reasons. Most important patient-related reasons were patients' preference of taking treatment closer to their native place (26.2%), lack of interest (16.8%) in trial participation. Anticipated poor compliance to treatment (5.9%) and follow-up (6.6%), inability to start treatment in time (6.2%) were important trial-related reasons for non enrollment. Multivariate analysis identified the genders (female), education (illiterate), occupation (laborer) and non availability of support system in the city as significant predictors of non-enrollment. CONCLUSIONS: Both trial design and patient factors were important causes of non enrollment in eligible patients. Patients' need for being closer to home and refusal to participate were the most common reasons for non-enrollment. PMID- 22322739 TI - High expression of the longevity gene product SIRT1 and apoptosis induction by sirtinol in adult T-cell leukemia cells. AB - Adult T-cell leukemia-lymphoma (ATL) is an aggressive peripheral T-cell neoplasm that develops after long-term infection with human T-cell leukemia virus (HTLV 1). SIRT1, a nicotinamide adenine dinucleotide(+)-dependent histone/protein deacetylase, plays a crucial role in various physiological processes, such as aging, metabolism, neurogenesis and apoptosis, owing to its ability to deacetylate numerous substrates, such as histone and NF-kappaB, which is implicated as an exacerbation factor in ATL. Here, we assessed how SIRT1 is regulated in primary ATL cells and leukemic cell lines. SIRT1 expression in ATL patients was significantly higher than that in healthy controls, especially in the acute type. Sirtinol, a SIRT1 inhibitor, induced significant growth inhibition or apoptosis in cells from ATL patients and leukemic cell lines, especially HTLV-1-related cell lines. Sirtinol-induced apoptosis was mediated by activation of the caspase family and degradation of SIRT1 in the nucleus. Furthermore, SIRT1 knockdown by SIRT1-specific small interfering RNA caused apoptosis via activation of caspase-3 and PARP in MT-2 cells, HTLV-1-related cell line. These results suggest that SIRT1 is a crucial antiapoptotic molecule in ATL cells and that SIRT1 inhibitors may be useful therapeutic agents for leukemia, especially in patients with ATL. PMID- 22322740 TI - Construction of highly functional alpha-amino nitriles via a novel multicomponent tandem organocatalytic reaction: a facile access to alpha-methylene gamma lactams. AB - The first tertiary amine-catalyzed multicomponent tandem Strecker-allylic alkylation (SAA) reaction has been developed, which provides a facile access to functionalized alpha-amino nitriles, which could be readily converted into alpha methylene-gamma-butyrolactams. PMID- 22322741 TI - A job for life or for living? PMID- 22322742 TI - Communist witch hunt. PMID- 22322743 TI - Countersignature code. PMID- 22322744 TI - Where does change begin? PMID- 22322745 TI - No place for complacency. PMID- 22322746 TI - A distinct sadness. PMID- 22322747 TI - Lego of that. PMID- 22322758 TI - General Dental Council: new Chair--new challenges. PMID- 22322759 TI - Contemporary dental practice in the UK in 2008: indirect restorations and fixed prosthodontics. AB - OBJECTIVES: To investigate, by postal questionnaire, various aspects of primary dental care provision in the United Kingdom. Additionally, to compare the results of this survey with a similar survey completed four years previously. METHODS: A questionnaire containing 89 questions was sent to 1,000 general dental practitioners selected at random from databases of practitioners throughout the United Kingdom. Non-responders were sent another questionnaire after a period of four weeks had elapsed. RESULTS: Overall a response rate of 66.2% was achieved. Amalgam was the preferred material for the core build up of vital teeth for 65% of the respondents. Dentine pins were still being used by practitioners, with stainless steel pins being preferred by 34% of respondents. 39.7% of dentists that had graduated between 0-10 years previously reported using no pins. Indirect posts were still used most widely, by 55% of the practitioners in the study, with increasing use of fibre posts noted (34%). Addition cured silicone impression materials were still the most frequently used impression material (71%) with reduced use (10%) of condensation cured silicone impression materials recorded. Glass ionomer luting cements (48%) and zinc phosphate (28%) were the most commonly used luting cements. CONCLUSIONS: Within the limitations of this study, the following conclusions can be drawn: amalgam is still the preferred material for the core build-up of vital teeth; dentine pins are still used widely, but not by younger practitioners; fibre posts are being increasingly used by practitioners; addition cured silicone is still the most widely used impression material; traditional glass ionomer cements are still the most widely used luting cements; veneers are still the preferred indirect restoration for restoring anterior teeth; and CAD/CAM systems are increasingly being used by practitioners. PMID- 22322760 TI - Current concepts on the management of tooth wear: part 3. Active restorative care 2: the management of generalised tooth wear. AB - Paper 3 of this series on the current concepts of tooth wear management will focus on the provision of active restorative intervention for cases presenting with generalised tooth wear. The use of both contemporary adhesive and traditional conventional techniques applied to treat cases of generalised tooth wear will be discussed, including a consideration of the merits and drawbacks of each approach respectively. PMID- 22322765 TI - Summary of: complexities associated with orthodontic services in the National Health Service. AB - AIM: To detail orthodontic provision in Wales. BACKGROUND: In 2006 the new orthodontic contract was introduced in the NHS in England and Wales. Since the introduction of the new contract there have been recent reports of inefficiencies in orthodontic provision in Wales in terms of: orthodontic provision reaching those who need it, type of orthodontic activities undertaken, who is providing orthodontic care, the relative cost-efficiency of the orthodontic services, contracting and performance management of the services and robustness of the orthodontic database. MATERIALS AND METHODS: 2008/09 orthodontic data on contracted services were analysed. Data from the salaried services was collected through a questionnaire. Normative orthodontic treatment need was estimated from mid-year population estimates. RESULTS: In 2008/09, there were considerable inefficiencies in the orthodontic services in Wales with varied level of access by children living in 22 former local health boards, co-terminus with local authorities in Wales. Total spend on orthodontics in Wales was around L12,718,370. It was estimated that 11,539 (30%) of 12-17-year-olds required orthodontic treatment. In 2008/09, 11,031 children received orthodontic treatment in all NHS services in Wales indicating a potential shortfall of 508 treatments. Out of 135 GDS/PDS orthodontic contracts, 27 provided no active treatment (only assessments) and 62 provided less than 50 treatments annually. Cost per units of orthodontic activity (UOA) ranged from L58 to L74. With improved contracts and efficiency, the orthodontic budget seems sufficient to meet the orthodontic need of the population. CONCLUSIONS: As with any type of NHS provision, it is important that orthodontic services are competitive, highly efficient and provided on the basis of need. Performance management of orthodontic services should focus on the number of successful orthodontic treatments delivered annually. The personal dental services (PDS) orthodontic contract will need to be modified accordingly. PMID- 22322766 TI - Summary of: compliance with pre-operative instructions for procedures with conscious sedation: a complete audit cycle. AB - INTRODUCTION: A wide variety of procedures in all surgical departments are performed under conscious sedation with midazolam. Patients are required to adhere to a list of pre-operative instructions but poor compliance has been noted anecdotally in our department and in the literature. This can lead to delayed and cancelled appointments. AIM: We aimed to audit the compliance of patients in following preoperative sedation instructions in the oral and maxillofacial department of a large tertiary teaching hospital with a view to improving compliance. All patients undergoing conscious sedation for day case procedures in a five month period were audited. We implemented changes based on findings and a literature review, followed by a second eight month period of audit. RESULTS: Twenty-nine and 30 patients participated in each cycle respectively. In the first cycle over 55% of patients were non-compliant. The most common reasons were not bringing a competent adult escort at the start of the appointment (17% of total) and having consumed alcohol in the 24 hours pre-operatively (17%). Based on this, the patient information leaflet was revised. Patients received copies when being listed and then with their posted appointment letter, as well as being verbally reminded before attending. Second cycle results revealed a 22% increase in compliance rates across all instructions with all patients bringing competent escorts along. CONCLUSIONS: Efficacy within the NHS is often achieved with simple and practical improvement to clinical and administrative practice. By achieving a reduction in non-compliance rates, the department was able to reduce appointment delays and waiting lists, ultimately to the patients' benefit. PMID- 22322767 TI - In-patient operating exposure for dental undergraduates: a valuable experience? AB - The General Dental Council, the Association of Dental Education in Europe and the Association of British Academic Oral and Maxillofacial Surgeons have all issued syllabuses suggesting undergraduate dental students should gain experience of oral and maxillofacial in-patient operating.Aim To examine whether final year dental students in a UK dental school had observed, and were comfortable providing an explanation of, oral and maxillofacial in-patient operating.Materials and methods Students at Newcastle University's School of Dental Sciences have block allocations to in-patient operating (16 half-day sessions). A questionnaire was distributed to the whole of the final year (n = 78) at the end of these allocations examining different aspects of their exposure to in-patient operating.Results A response rate of 81% (n = 63) was achieved. Those responding reported that they had seen a wide variety of surgery. The most common procedural group that had not been observed was orthognathic surgery (n = 33, 52%). There was no correlation (p >0.05) between total number of procedural groups observed and total number of procedural groups that students were confident to explain, although there were significant correlations (p <0.05) between having observed specific operations and having the confidence to explain them. The students felt that the block allocations were beneficial (n = 46, 63%) and offered a variety of free-text reasons for this. Only a minority (n = 24, 38%) had been actively involved in the surgery they had observed, the majority of those individuals having undertaken some suturing (n = 11).Conclusions Students perceive allocations to oral and maxillofacial in-patient operating as beneficial for a variety of reasons. The relationship between having observed a procedure and the individual's perceived ability to explain it appears to be complex. It is difficult to achieve consistent exposure throughout a large year group of undergraduate students, but more targeted learning may be of benefit. PMID- 22322784 TI - Complexities associated with orthodontic services in the National Health Service. AB - AIM: To detail orthodontic provision in Wales. BACKGROUND: In 2006 the new orthodontic contract was introduced in the NHS in England and Wales. Since the introduction of the new contract there have been recent reports of inefficiencies in orthodontic provision in Wales in terms of: orthodontic provision reaching those who need it, type of orthodontic activities undertaken, who is providing orthodontic care, the relative cost-efficiency of the orthodontic services, contracting and performance management of the services and robustness of the orthodontic database. MATERIALS AND METHODS: 2008/09 orthodontic data on contracted services were analysed. Data from the salaried services was collected through a questionnaire. Normative orthodontic treatment need was estimated from mid-year population estimates. RESULTS: In 2008/09, there were considerable inefficiencies in the orthodontic services in Wales with varied level of access by children living in 22 former local health boards, co-terminus with local authorities in Wales. Total spend on orthodontics in Wales was around L12,718,370. It was estimated that 11,539 (30%) of 12-17-year-olds required orthodontic treatment. In 2008/09, 11,031 children received orthodontic treatment in all NHS services in Wales indicating a potential shortfall of 508 treatments. Out of 135 GDS/PDS orthodontic contracts, 27 provided no active treatment (only assessments) and 62 provided less than 50 treatments annually. Cost per units of orthodontic activity (UOA) ranged from L58 to L74. With improved contracts and efficiency, the orthodontic budget seems sufficient to meet the orthodontic need of the population. CONCLUSIONS: As with any type of NHS provision, it is important that orthodontic services are competitive, highly efficient and provided on the basis of need. Performance management of orthodontic services should focus on the number of successful orthodontic treatments delivered annually. The personal dental services (PDS) orthodontic contract will need to be modified accordingly. PMID- 22322785 TI - Compliance with pre-operative instructions for procedures with conscious sedation: a complete audit cycle. AB - INTRODUCTION: A wide variety of procedures in all surgical departments are performed under conscious sedation with midazolam. Patients are required to adhere to a list of pre-operative instructions but poor compliance has been noted anecdotally in our department and in the literature. This can lead to delayed and cancelled appointments. AIM: We aimed to audit the compliance of patients in following preoperative sedation instructions in the oral and maxillofacial department of a large tertiary teaching hospital with a view to improving compliance. All patients undergoing conscious sedation for day case procedures in a five month period were audited. We implemented changes based on findings and a literature review, followed by a second eight month period of audit. RESULTS: Twenty-nine and 30 patients participated in each cycle respectively. In the first cycle over 55% of patients were non-compliant. The most common reasons were not bringing a competent adult escort at the start of the appointment (17% of total) and having consumed alcohol in the 24 hours pre-operatively (17%). Based on this, the patient information leaflet was revised. Patients received copies when being listed and then with their posted appointment letter, as well as being verbally reminded before attending. Second cycle results revealed a 22% increase in compliance rates across all instructions with all patients bringing competent escorts along. CONCLUSIONS: Efficacy within the NHS is often achieved with simple and practical improvement to clinical and administrative practice. By achieving a reduction in non-compliance rates, the department was able to reduce appointment delays and waiting lists, ultimately to the patients' benefit. PMID- 22322786 TI - Preparation and characterization of novel multi-core chitosan microspheres for stomach-specific delivery of hydrophilic antibiotics. AB - Insufficient gastric mucosa drug concentration and short contact time were the main reason for the lack of eradication efficacy of Helicobacter pylori for peptic ulcer patients. Novel multi-core chitosan microspheres were prepared for stomach-specific delivery of hydrophilic antibiotics for the treatment of peptic ulcer. Chitosan microspheres with multiple Eudragit L100 cores were easily prepared by a new emulsification/coagulation encapsulating method. Swelling behaviors, surface amino groups and mucin absorption ability were investigated and the formulation that showed best mucoadhesive potential was adopted. The multi-core chitosan microspheres exhibited good mucoadhesiveness as well as controlled release manner for incorporated antibiotics in acidic environment. The release rate could be easily modulated with accumulative release ranging from 47.3 to 79.3% in 6 h. Accordingly, the multi-core chitosan microspheres could serve as a satisfactory vehicle for stomach-specific delivery of hydrophilic antibiotics. PMID- 22322787 TI - In brief: Mayfield et al. Classification: carpal dislocations and progressive perilunar instability. PMID- 22322788 TI - Diffusion and segregation of niobium in fcc-nickel. AB - Niobium is one of the major alloying elements, among the refractory elements, contributing to the strengthening of superalloys. Consequently, data about its behavior and its migration mechanism in fcc-Ni are essential knowledge to understand and control the strengthening in such alloys. We present in this work Nb interactions, solubility and diffusion in Ni performed by using the GGA approximation of the density functional theory. The substituted site is found to be the most favorable configuration in comparison to the tetrahedral and octahedral sites. The effect of temperature on solubility is discussed taking into account the thermal expansion of the lattice parameter and the vibrational contribution. Its diffusion mechanism is also discussed and compared to the literature. We finally discuss the segregation of Nb atoms on a Sigma(5)-(012) symmetric tilt grain boundary. PMID- 22322789 TI - An experimental study on the effect of substituents on aromatic-aromatic interactions in dithia[3,3]-metaparacyclophanes. AB - Simple model systems based on the 2,11-dithia[3,3]-metaparacyclophane skeleton were synthesized to study the effects of substituents on the intramolecular aromatic-aromatic interactions between benzene rings. X-ray crystallography established that, in their more stable conformations, these metaparacyclophanes featured partially overlapping aromatic rings (interplanar distances of about 3.5 A), with the planes of the aromatic systems arranged in a slightly tilted disposition (interplanar angles in the range 5-19 degrees ). Calculations showed that these derivatives underwent topomerization by flipping of the meta substituted ring over the para-substituted one, a process in which the two rings adopted a continuum of edge-to-face dispositions, including an orthogonal one, which were less stable than the starting face-to-face arrangement. The energy barriers to the isomerization process were experimentally determined by variable temperature NMR spectroscopy, by using an internal temperature standard to assess even minor differences in energy (relative experimental error: (+/-0.1 kJ mol( 1)). The variation in the barriers as a function of the different substituents on the interacting ring was small and apparently unrelated to the effect of the substituents on the polarity of the pi-systems. An explanation based on the charge-penetration effect seemed more-suitable to rationalize the observed trends in the barriers. PMID- 22322790 TI - Further support for the early administration of lipid emulsion in the treatment of ropivacaine-induced central nervous system toxicity. PMID- 22322791 TI - [Efficacy of artemether-lumefantrine in the treatment of uncomplicated malaria in children living in a rural area of Burkina Faso in 2009]. AB - In order to implement community case management of malaria strategy in a rural area of intense transmission, of children using artemether-lumefantrine combination, we assessed the therapeutic efficacy of the medicine. We conducted an open label and uncontrolled clinical trial in an unique centre from September 2009 to December 2009 in children 6-59 months old who consulted at health facilities for uncomplicated malaria. The primary endpoint was clinical and parasitological cure rate at day 28 corrected by PCR. In total 106 children were enrolled. Parasite clearance at day 2 was 99.04% and the adequate clinical and parasitological response corrected by PCR at day 28 was 90.5%. Our results confirm that artemether-lumefantrine combination is still effective. PMID- 22322794 TI - A theoretical study of the OH-initiated gas-phase oxidation mechanism of beta pinene (C10H16): first generation products. AB - An extensive mechanism for the OH-initiated oxidation of beta-pinene up to the first-generation products was derived based on quantum chemical calculations, theoretical kinetics, and structure-activity relationships. The resulting mechanism deviates from earlier explicit mechanisms in several key areas, leading to a different product yield prediction. Under oxidative conditions, the inclusion of ring closure reactions of unsaturated alkoxy radicals brings the predicted nopinone and acetone yields to an agreement with the experimental data. Routes to the formation of other observed products, either speciated or observed as peaks in mass spectrometric studies, are also discussed. In pristine conditions, we predict significant acetone formation following ring closure reactions in alkylperoxy radicals; in addition, we predict some direct OH recycling in subsequent H-migration reactions in alkylperoxy radicals. The uncertainties on the key reactions are discussed. Overall, the OH-initiated oxidation of beta-pinene is characterized by the formation of a few main products, and a very large number of products in minor to very small yields. PMID- 22322795 TI - War-related PTSD, blast injury, and anosognosia. PMID- 22322796 TI - [Prevention of periprosthetic joint infections]. AB - High numbers of primary joint replacement procedures lead to increasing numbers of revision surgeries due to periprosthetic joint infections. Several studies revealed different patient-associated and intervention-associated risk factors. Importance should be pointed on short operating times to avoid intraoperative colonisation of the implant with microorganisms. Patient-associated diseases such as diabetes and obesity should be influenced positively in the preoperative setting. Cessation of smoking should be started two months before surgery and continued until wound healing is completed. Intraoperative single-shot antibiotic prophylaxis has become clinical routine. Prolonged perioperative antibiotic prophylaxis is often conducted but has not shown to be effective in lowering infection rates. PMID- 22322798 TI - Rapid eye movement sleep behavior disorder and risk of dementia in Parkinson's disease: a prospective study. AB - One of the most devastating nonmotor manifestations of PD is dementia. There are few established predictors of dementia in PD. In numerous cross-sectional studies, patients with rapid eye movement (REM) sleep behavior disorder (RBD) have increased cognitive impairment on neuropsychological testing, but no prospective studies have assessed whether RBD can predict Parkinson's dementia. PD patients who were free of dementia were enrolled in a prospective follow-up of a previously published cross-sectional study. All patients had a polysomnogram at baseline. Over a mean 4-year follow-up, the incidence of dementia was assessed in those with or without RBD at baseline using regression analysis, adjusting for age, sex, disease duration, and follow-up duration. Of 61 eligible patients, 45 (74%) were assessed and 42 were included in a full analysis. Twenty-seven patients had baseline RBD, and 15 did not. Four years after the initial evaluation, 48% with RBD developed dementia, compared to 0% of those without (P adjusted = 0.014). All 13 patients who developed dementia had mild cognitive impairment on baseline examination. Baseline REM sleep atonia loss predicted development of dementia (% tonic REM = 73.2 +/- 26.7 with dementia, 40.8 +/- 34.5 without; P = 0.029). RBD at baseline also predicted the new development of hallucinations and cognitive fluctuations. In this prospective study, RBD was associated with increased risk of dementia. This indicates that RBD may be a marker of a relatively diffuse, complex subtype of PD. PMID- 22322799 TI - Recent progress of on-line sample preconcentration techniques in microchip electrophoresis. AB - This review highlights recent developments and applications of on-line sample preconcentration techniques to enhance the detection sensitivity in microchip electrophoresis (MCE); references are mainly from 2008 and later. Among various developed techniques, we focus on the sample preconcentration based on the changes in the migration velocity of analytes in two or three discontinuous solutions system, since they can provide the sensitivity enhancement with relatively easy experimental procedures and short analysis times. The characteristic features of the on-line sample preconcentration applied to microchip electrophoresis (MCE) are presented, categorized on the basis of "field strength-" or "chemically" induced changes in the migration velocity. The preconcentration techniques utilizing field strength-induced changes in the velocity include field-amplified sample stacking, isotachophoresis and transient isotachophoresis, whereas those based on chemically induced changes in the velocity are sweeping, transient-trapping and dynamic pH junction. PMID- 22322800 TI - A system for the rapid determination of the mutation spectrum in Escherichia coli. AB - The first step toward elucidating the mutagenic effects of chemicals and pathways is to determine the specificity of the mutations generated spontaneously or in response to treatment with mutagens. We constructed a set of plasmid-encoded probes for the specific detection of each type of base substitution mutation. Using these probes, we were able to quickly determine both the mutation rate and the specificity of the mutations caused by different types of mutagens and mutagenic conditions. We also developed a PCR-based method to rapidly and robustly determine the mutation spectrum in response to various mutagenic samples in parallel. This system allows one to not only analyze the mutation specificity of various chemicals, but also to search for novel genetic elements that promote the specific mutation events. PMID- 22322801 TI - Reevaluation of donor number using titration calorimetry. AB - Many empirical parameters have been suggested to measure solvent effects in chemical reactions. Gutmann's donor number has been a successful parameter to quantify the electron-donating property of the solvent molecule; it is defined as the enthalpy change of the addition reaction of solvent molecule to SbCl(5) in 1,2-dichloroethane. Calorimetric measurements can be applied to determine the quantity. Because the existence of water is critical for reactions in organic solvents, we have analyzed the enthalpy change using the titration calorimetry while considering the complexation with water. The determined donor numbers of formamide, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and 1,1,3,3 tetramethylurea (TMU) are 22.4, 26.5, 30.0, and 40.4, respectively. The values of DMF and DMSO are in perfect agreement with those of Gutmann. A reliable value for TMU is obtained for the first time on the basis of the enthalpy change for the addition reaction. PMID- 22322802 TI - Sensitive and selective electrochemical detection of carbon monoxide in saline at a Pt-Ru/Nafion/MnO2-modified electrode. AB - We fabricated a sensitive and selective electrochemical carbon monoxide (CO) sensor for physiological conditions based on the Pt-Ru system. At a bare Pt-Ru electrode, a linear amperometric response to CO concentration was obtained in the range of 0.9-9 uM. However, significant current response to model electroactive interferents for physiological conditions, uric acid (UA), ascorbic acid (AA) and hydrogen peroxide (HP), was also recorded at the Pt-Ru electrode. The response to UA and AA was highly suppressed by coating the Pt-Ru electrode surface with a Nafion layer, and the response to HP was almost completely eliminated by the additional coating with a MnO(2)/chitosan layer. Finally, at the Pt Ru/Nafion/MnO(2) electrode, amperometric CO detection with a sensitivity of 173 nA cm(-2) uM(-1) was obtained in the concentration range of 0.9-9 uM with the UA, AA and HP signal being below 1.7% at the same concentration of CO. PMID- 22322803 TI - Glucose recognition by a supramolecular complex of boronic acid fluorophore with boronic acid-modified cyclodextrin in water. AB - A boronic acid fluorophore (C1-APB)/boronic acid-modified gamma-cyclodextrin (3 PB-gamma-CyD) complex as a supramolecular sensor has been designed for selective glucose recognition in water. The fluorescent response behavior of the C1-APB/3 PB-gamma-CyD complex under various pH conditions revealed that a C1-APB/3-PB gamma-CyD complex solution containing glucose showed a large increase in the fluorescence intensity under alkaline pH conditions. In contrast, only small increases in the fluorescence intensity were noted for fructose and without sugar solutions. The observed response selectivity for the C1-APB/3-PB-gamma-CyD complex was on the order of glucose >> galactose, mannose > fructose. The evidence on a large value of the inclusion constant (K(L.CyD) = 6.5 * 10(3) M( 1)), a marked broadening of the (1)H NMR spectra, and an enhancement of induced circular dichloism (ICD) intensity for the C1-APB/3-PB-gamma-CyD complex by glucose binding supported the multi-point interaction of the C1-APB/3-PB-gamma CyD complex with glucose. These results demonstrated that the C1-APB/3-PB-gamma CyD complex functioned as an efficient supramolecular sensor for selective glucose recognition in water. PMID- 22322804 TI - Electrochemical detection of sugar-related compounds using boron-doped diamond electrodes. AB - Electrochemical detection of sugar-related compounds was conducted using a boron doped diamond (BDD) electrode as a detector for flow-injection analysis (FIA). Sugar-related compounds oxidize at high applied potentials, for which the BDD electrode is suitable for electrochemical measurements. Conditions for an FIA system with a BDD detector were optimized, and the following detection limits were achieved for sugar-related compounds: monosaccharides, 25-100 pmol; sugar alcohols, 10 pmol; and oligosaccharides, 10 pmol. The detection limit for monosaccharide D-glucose (Glu) was 105 pmol (S/N = 3). A linear range was acquired from the detection limit to 50 nmol, and the relative standard deviation was 0.65% (20 nmol, n = 6). A high-performance liquid chromatography (HPLC) column was added to the system between the sample injector and the detector and detection limits to the picomole level were achieved, which is the same for the HPLC system and the FIA system. The electrochemical oxidation reaction of Glu was examined using cyclic voltammetry with the BDD detector. The reaction proved to be irreversible, and proceeded according to the following two-step mechanism: (1) application of a high potential (2.00 V vs. Ag/AgCl) to the electrode causes water to electrolyze on the electrode surface with the simultaneous generation of a hydroxyl radical on the surface, and (2) the hydroxyl radical indirectly oxidizes Glu. Thus, Glu can be detected by an increase in the oxidation current caused by reactions with hydroxy radicals. PMID- 22322805 TI - Inkjet printed Prussian blue films for hydrogen peroxide detection. AB - An inkjet printing method is described to fabricate hydrogen peroxide (H(2)O(2)) sensors. Insoluble Prussian blue (PB) nanoparticles were dispersed in aqueous solvent, and were printed on screen printed carbon electrodes with a piezoelectric inkjet printer for H(2)O(2) detection. The electrochemical behavior of the printed sensors was studied by using cyclic voltammetry and chronoamperometry. The printed sensors showed great electrocatalytic activity toward H(2)O(2) and can be used for amperometric detection of H(2)O(2). The calibration curves for H(2)O(2) determination showed a linear range from 0.02 to 0.7 mM with a sensitivity of 164.82 uA M(-1) cm(-2) for the printed PB film. The results showed the feasibility of applying inkjet printing technology on surface modification; the results also provide an alternative way for manufacturing electrochemical sensors. PMID- 22322806 TI - Highly sensitive determination of cadmium and lead using a low-cost electrochemical flow-through cell based on a carbon paste electrode. AB - A low-cost thin-layer electrochemical flow-through cell based on a carbon paste electrode (CPE), was constructed for the highly sensitive determination of cadmium(II) (Cd(2+)) and lead(II) (Pb(2+)) ions. The sensitivity of the proposed cell for Cd(2+) and Pb(2+) ion detection was improved by using the smallest channel height without the need for any complicated electrode modification. Under the optimum conditions, the detection limits of Cd(2+) and Pb(2+) ions (0.08 and 0.07 ug dm(-3), respectively) were 13.8- and 11.4-fold lower than that of a commercial flow cell (1.1 and 0.8 ug dm(-3), respectively). Moreover, the percentage recoveries of Cd(2+) and Pb(2+) for the in-house designed thin-layer flow cell were higher than those for the commercially available cell in all tested water samples, and within the acceptable range. The proposed flow cell is promising as an inexpensive and alternative one for the highly sensitive monitoring of heavy metal ions. PMID- 22322807 TI - Selective determination of epinephrine in the presence of ascorbic acid using a glassy carbon electrode modified with graphene. AB - A graphene-modified glassy carbon electrode was fabricated via a drop-casting method, and applied to the electrochemical detection of epinephrine. The capacity of the graphene-modified glassy carbon electrode for the selective detection of epinephrine was confirmed in a sufficient amount of ascorbic acid (2 mmol L(-1)) by cyclic voltammetry. The modified electrode showed an excellent electrocatalytical effect on the oxidation of epinephrine. A pair of well-defined redox waves were observed in voltammograms of epinephrine in a phosphate buffered solution (pH 4.0). The peak potentials of epinephrine remained unchanged, and the oxidation peak currents showed a linear relation versus the epinephrine concentration in the range of 3.85 * 10(-7) - 1.31 * 10(-5) mol L(-1) and 1.31 * 10(-5) - 1.09 * 10(-4) mol L(-1) with a correlation coefficient as follows: i(pa1) = -4.25 * 10(-6) - 1.99c (mol L(-1)), R(1) = 0.9953; i(pa2) = -4.31 * 10( 5) - 0.315c (mol L(-1)), R(2) = 0.9988. Detection limit is estimated to be 8.9 * 10(-8) mol L(-1). Graphene-modified glassy carbon electrode was applied to epinephrine sample analysis, and the results were in good agreement with the standard values. PMID- 22322808 TI - Dye-doped nanostructure polypyrrole film for electrochemically switching solid phase microextraction of Ni(II) and ICP-OES analysis of waste water. AB - A nanostructure fiber based on conducting polypyrrole synthesized by an electrochemical method has been developed, and used for electrochemically switching solid-phase microextraction (ES-SPME). The ES-SPME was prepared by the doping of eriochrome blue in polypyrrole (PPy-ECB) and used for selectively extracting the Ni(II) cation in the presence of some transition and heavy metal ions. The cation-exchange behavior of electrochemically prepared polypyrrole on stainless-steel with and without eriochrome blue (ECB) dye was characterized using ICP-OES analysis. The effects of the scan rate for electrochemical synthesis, uptake and the release potential on the extraction behavior of the PPy ECB conductive fiber were studied. Uptake and release time profiles show that the process of electrically switched cation exchange could be completed within 250 s. The results of the present study point concerning the possibility of developing a selective extraction process for Ni(II) from waste water was explored using such a nanostructured PPy-ECB film through an electrically switched cation exchange. PMID- 22322809 TI - Method validation by interlaboratory studies of improved hydrophilic oxygen radical absorbance capacity methods for the determination of antioxidant capacities of antioxidant solutions and food extracts. AB - Hydrophilic oxygen radical absorbance capacity (H-ORAC) is a method for evaluating antioxidant capacities of solutions of hydrophilic compounds. In this study, we improved the original method for H-ORAC determination, and evaluated the precision of the two improved methods (methods A and B) by interlaboratory studies using 5 antioxidant solutions and 5 food extracts as test samples. An interlaboratory study of method A, in accordance with the harmonized protocol, demonstrated satisfactory performance (intermediate precision relative standard deviations (RSD(int)) ranging from 4.6 to 18.8%; the reproducibility relative standard deviations (RSD(R)) ranging from 7.0 to 21.1%, and the HorRat values ranging from 0.40 to 1.93). However, methodological problems remained, and a further improved method, method B, was thus developed. An interlaboratory study of method B by 5 participating laboratories showed better intermediate precision and reproducibility (RSD(int) and RSD(R) ranging from 1.8 to 9.4%, and from 4.4 to 13.8%, respectively), and all HorRat values for the test samples were less than 1.3, suggesting good performance for the H-ORAC measurement. PMID- 22322810 TI - Development of a screening method for the determination of PCBs in water using QuEChERS extraction and gas chromatography-triple quadrupole mass spectrometry. AB - A new method has been developed and validated for the simultaneous analysis of 11 polychlorinated biphenyls (PCBs), in water samples at trace levels by gas chromatography coupled to triple quadrupole mass spectrometry (GC-QqQ-MS/MS). Water samples were extracted by the QuEChERS (Quick Easy Cheap Effective Rugged and Safe) method. The QqQ analyzer acquired data in multiple reactions monitoring (MRM), permitting both quantification and confirmation in a single injection with a running time reduced up to 11.0 min. The effect of matrix interferences in extracts on analyte quantification and the identification of PCBs in water samples was deeply studied. The results showed that PCBs were prone to strong matrix interactions in water samples, and the quantification and identification of PCBs were highly affected by a matrix enhancement effect. To evaluate the performance of the method, validation experiments were carried out on water samples at three spiking levels (1.6, 8.0, 40.0 ug L(-1)). Recovery was in the range of 95 - 109% at 1.6 ug L(-1), 90 - 95% at 8.0 ug L(-1) and 97 - 102% at 40.0 ug L(-1), respectively. Precision values expressed as relative standard deviation (RSD) were lower than 15%. Linearity in the range of 0.5 - 50.0 ug L( 1) provided determination coefficients (R(2)) higher than 0.999 for all compounds. The limits of detection (LODs) for PCBs were <=0.1 ug L(-1) and the limits of quantification (LOQs) ranged from 0.04 to 0.3 ug L(-1). The applicability of the proposed method to detect and quantify PCBs has been demonstrated in analyse of 15 real samples. PMID- 22322811 TI - Simultaneous determination of five polyether ionophores using liquid chromatography with one-step fluorescent derivatization. AB - We present a selective method for simultaneous determination of five polyether ionophores such as salinomycin (SAL), monensin (MON), narasin (NAR), semduramicin (SEM) and lasalocid (LAS) in aquatic samples using a liquid chromatography with one-step fluorescent derivatization of 2-(4-hydrazinocarbonyl-phenyl) 4,5 diphenylimidazole (HCPI) and 4-(4,5-diphenyl-1H-imidazol-2-yl) benzoyl chloride hydrochloride (DIB-Cl). Fluorescent one-step derivatization for SAL, MON, NAR and SEM using HCPI and for LAS using DIB-Cl was monitored by an LC/fluorescence detector (E(x), 340 nm; E(m), 465 nm). Chromatographic separation was performed on a TSK-GEL ODS-120T (4.6 * 150 mm, 3 um) column using a mobile phase of 0.1% formic acid in acetonitrile and 0.5 mM ammonium formate in water (70/30, v/v). The limits of detections were 0.01 ug/mL (50 pg) for LAS, 0.05 ug/mL (250 pg) for SAL, NAR and SEM, and 0.1 ug/mL (500 pg) for MON, respectively. The recoveries for water samples were indicated to be the range of 79.6 +/- 6.4 - 99.0 +/- 4.4% with associated precision values (between-day for 3 days) for repeatability. Based on solid-phase extraction, the limit of quantitation values indicated 0.1 ng/mL for SAL, MON, NAR and SEM, and 0.01 ng/mL for LAS in water samples. PMID- 22322812 TI - Determination of histamine in seafood by hydrophilic interaction chromatography/tandem mass spectrometry. AB - A simple method was developed to determine histamine, an important compound in chemical food poisoning, by extraction followed by hydrophilic interaction chromatography-tandem mass spectrometry using a hydrophilic column with sulfobetaine-type zwitterion groups. The quantitation range in seafood products was from 0.4 to 200 mg kg(-1) for 5 g food samples. Quantitative recoveries were obtained with four types of seafood product. These results agreed well with those from the more complex, conventional HPLC method, which requires sample derivatization with dansyl chloride. PMID- 22322813 TI - Modification of electroosmotic flow for a polydimethylsiloxane electrophoresis microchip via polyelectrolyte coating. AB - Polydimethylsiloxane has been dominantly employed as the substrate material for microchip capillary electrophoresis. The poor surface chemistry, however, generates inconsistent electroosmotic flow under the electrophoretic condition, limiting its broader applications. In this work, different polyelectrolytes, including polydiallyldimethylammonium chloride, polyvinyl sulfate, and dextran sulfate, were successfully deposited onto polydimethylsiloxane microchannel surfaces. The polyelectrolyte coated polydimethylsiloxane microchannel showed improved consistency and reproducibility in electroosmotic flow under an electric field over the uncoated native microchannel. PMID- 22322814 TI - Development of an electrochemical cholesterol sensor system for food analysis. AB - In this article, we report on a food-cholesterol monitoring sensor based on a non enzymatic approach. Amorphous and single-crystal gold electrodes were modified with an alkanethiol self-assembled monolayer to quantify it by voltammetry. We first discuss the basic characteristics of these sensors and provide more information about the instrument developed by JSK Co. This instrument is a battery-operated handheld voltammetric analyzer, which mounts a sensor chip to monitor cholesterol contents in food samples. The sensor showed excellent linearity with the cholesterol concentration; egg-yolk samples were analyzed to give an excellent agreement between the values obtained by the sensor (1.4 mM) and chromatography (1.1 mM). PMID- 22322815 TI - Role of erythropoietin in prevention of amikacin-induced nephropathy. AB - BACKGROUND: Aminoglycoside antibiotics are widely used potent bactericidal drugs. However, nephrotoxicity side effects via oxidant injury limit their effectiveness. Erythropoietin (Epo) has been shown to exert pleiotropic effects besides promoting erythrocyte differentiation such as antiapoptotic, antioxidant functions in ischemic and toxic acute renal injury. Therefore we aimed to explore whether Epo is renoprotective in an amikacin-induced nephropathy model in rats. METHODS: Twenty-eight rats were distributed equally into 4 groups: (i) injected with saline, (ii) injected with amikacin (1.2 g/kg intraperitoneally [i.p.]), (iii) pretreated with Epo (2,000 IU/kg, i.p.) and amikacin (1.2 g/kg i.p.) and (iv) injected only with Epo (2,000 IU/kg, i.p.). Twenty-four hours after last injection, renal tissues were excised for histopathological examinations, and blood samples were collected for serum creatinine and blood urea nitrogen measurements. RESULTS: An approximately twofold elevation in blood urea nitrogen concentration in the amikacin group (26.6 +/- 3.9 mg/dL) compared with saline group (13.1 +/- 0.4 mg/dL) was found, reflecting a significant degree of renal dysfunction (p<0.01). Serum urea levels were significantly improved in rats pretreated with Epo (15.9 +/- 0.9 mg/dL). The most severe and pronounced injuries based on tubular necrosis were observed in the amikacin group, while rats pretreated with Epo demonstrated marked reduction of the histological features of renal injury. CONCLUSION: As far as we know, the present results are the first to demonstrate a protective effect of exogenous Epo against experimental amikacin induced renal injury. According to these results, Epo may improve the therapeutic potential of amikacin. More studies are needed for a final conclusion. PMID- 22322816 TI - A case of valproic acid-induced acute pancreatitis in tuberous sclerosis coexisting with end-stage renal disease. AB - Tuberous sclerosis complex (TCS) is a genetic disorder with a variable clinical presentation. It is commonly characterized by seizures, mental retardation and cutaneous angiofibromas. Renal manifestations frequently include angiomyolipomas and cysts which lead to chronic kidney disease. We report a case of valproic acid induced acute pancreatitis in a dialysis patient affected by TCS. The case demonstrates the importance of assessing antiepileptic drug treatment in dialysis patients. PMID- 22322817 TI - Efficacy and safety of rituximab treatment in children with primary glomerulonephritis. AB - BACKGROUND: The aim of our study was to analyze the efficacy and safety of rituximab, a chimeric monoclonal antibody against CD20 lymphocytes, as a nonstandard immunosuppressive therapy in children with different types of primary glomerulonephritis who were not eligible for routine treatment. METHODS: The study group was composed of 16 children with proteinuric glomerulopathies, not responding to standard immunosuppressive therapy. The indications included steroid-resistant nephrotic syndrome (n=14) and steroid-dependent nephrotic syndrome (n=2). The dose of rituximab was established as 375 mg/m2 of body surface area, administered by intravenous infusion once weekly for 1 to 4 weeks, depending on the CD19 lymphocyte count. We evaluated proteinuria and plasma concentration of CD19 lymphocytes at intervals of 1, 3 and 6 months, after which patients received a single repeat dose. RESULTS: Remission, defined as proteinuria less than 150 mg per 24 hours, was observed in 7 of the 16 children. There were no statistically significant differences in leukocyte counts between single and multiple rituximab doses. We also did not observe any clinical or biochemical side effects. CONCLUSIONS: In conclusion, we postulate that alternative rituximab therapy should be taken into consideration in nephrotic patients not responding to standard therapy. PMID- 22322818 TI - Creatinine- vs. cystatin C-based equations compared with 99mTcDTPA scintigraphy to assess glomerular filtration rate in chronic kidney disease. AB - BACKGROUND: In chronic kidney disease (CKD), accurate estimation of the glomerular filtration rate (GFR) is mandatory. Gold standard methods for its estimation are expensive and time-consuming. We compared creatinine- versus cystatin C-based equations to measure GFR, employing (99m)Tc-DTPA scintigraphy as the gold standard. METHODS: This was a prospective cross-sectional observational study including 300 subjects. CKD was defined according to K/DOQI guidelines, and patients were separated into groups: stage 1 (G1), n=26; stage 2 (G2), n=52; stage 3 (G3), n=90; stage 4 (G4), n=37; stage 5 (G5), n=60; and control group, n=35. Creatinine-based estimates were from 24-hour creatinine clearance using the Walser formula, Cockcroft-Gault, MDRD-4 and CKD-EPI; cystatin C equations used were Larsson, Larsson modified equation, Grubb and Hoek. RESULTS: Age and body mass index were different among groups; proteinuria, hypertension, diabetes and primary glomerulopathies significantly increased as CKD worsened. In the global assessment, CKD-EPI and Hoek gave the highest correlations with (99m)Tc-DTPA: rho=0.826, p<0.001 and rho=0.704, p<0.001, respectively. Most significant linear regressions obtained: CKD-EPI vs. (99m)Tc-DTPA, Hoek vs. (99m)Tc-DTPA and CKD-EPI vs. Hoek. However, important differences emerged when each group was analyzed separately. Best significant correlations obtained with (99m)Tc-DTPA: control group, creatinine clearance rho=0.421, p=0.012; G1, Crockoft-Gault rho=0.588, p=0.003; G2, CKD-EPI rho=0.462, p<0.05; G3, CKD-EPI rho=0.508, p<0.001; G4, Hoek rho=0.618, p<0.001; G5, CKD-EPI rho=0.604, p<0.001. CONCLUSIONS: At GFR <60 ml/min, CKD-EPI and Hoek equations appeared to best correlate with (99m)TcDTPA. In controls and at early stages of CKD, creatinine-based equations correlated better with (99m)Tc-DTPA, with CKD-EPI being the one with the best degree of agreement. PMID- 22322819 TI - ACE inhibitor or angiotensin II receptor blocker use is a risk factor for contrast-induced nephropathy. AB - BACKGROUND: The aim of the present study was to assess the influence of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) use on the incidence of contrast-induced nephropathy (CIN) in patients undergoing coronary angiography. METHODS: A retrospective case control study was conducted on a total of 201 patients divided into 2 groups (CIN group and control group). CIN was defined as an increase in serum creatinine by more than 25% from baseline within 48 hours of radiocontrast exposure. The CIN group had 96 patients, and the control group had 105 patients. The 2 groups were matched for variables such as age, sex, weight, baseline serum creatinine, diabetes, dye load, use of diuretics, statins and preprocedure prophylactic measures for CIN. RESULTS: The incidence of CIN was found to be 4.55%. The CIN group had 96 patients out of which 56 patients (58.3%) were on chronic ACEI or ARB, while the control group had 105 patients, but only 36 of patients (34.3%) were on ACEI or ARB (p<0.001).The odds ratio for development of CIN with respect to ACEI or ARB use was 2.68 (95% confidence interval, 1.51-4.76). CONCLUSION: Use of ACEI or ARB is an independent risk factor for developing CIN. It is reasonable to discontinue their use 48 hours prior to exposure to radiocontrast agents, especially in patients with multiple risk factors. PMID- 22322820 TI - Identification of drug-related problems in ambulatory chronic kidney disease patients: a 6-month prospective study. AB - BACKGROUND: Drug-related problems (DRPs) are common in chronic kidney disease (CKD) patients. We developed a 2-step consultation including a clinical pharmacist (CP) session and a nephrologist conventional care consultation to explore the feasibility of a pilot drug-oriented disease management program in controlling iatrogenic side effects. METHODS: Drug inventory was estimated by a CP before each nephrology consultation. CP interventions were based on the French Society of Clinical Pharmacy intervention tools. RESULTS: In this 6-month prospective study, 67 CKD patients were enrolled: 77% with stage 3 or 4 CKD (by Kidney Disease Improving Global Outcomes criteria), 66% males, 76% with diabetes, median age 70 years (range 59-75), with a mean 2.6 +/- 1.2 comorbidities and 10 +/- 3.5 medications. We registered 142 DRPs, in 93% of patients, which mainly concerned untreated indications (31.7%) and incorrect dosages (19%). The most frequent pharmaceutical interventions concerned addition of drug (34%) and adaptation of dose (25.5%). The main drugs involved concerned the cardiovascular (33%), digestive-metabolic (26.9%) and hematopoietic (19.9%) systems. DRPs correlated significantly with a higher number of medications (p=0.049) and with older patient age (p=0.0027). Furthermore, patients' knowledge was evaluated in 41 patients (61%) by the CP with a systematic questionnaire. Three at-risk situations were described: 80.5% of patients interviewed were unaware of the beneficial impact of their treatment, 85% were not aware of medical situations at risk and 68% declared self-medication habits. CONCLUSION: A formatted CP evaluation coupled with a renal consultation was able to detect a higher level of DRPs, to reinforce educational messages and to propose immediate changes in the therapeutic project. PMID- 22322821 TI - Isonatric dialysis biofeedback in hemodiafiltration with online regeneration of ultrafiltrate (HFR): rationale and study protocol for a randomized controlled study. AB - Dialysate sodium prescription has major implications for hemodialysis tolerance but also for dialyzed patients' cardiovascular morbidity as a determinant factor of blood pressure. Biofeedback systems have been developed to drive dialysate conductivity in order to reach a prescribed serum sodium concentration, indirectly evaluated by a dialysate or an ultrafiltrate conductivity measurement. A biofeedback system using hemodiafiltration with online regeneration of ultrafiltrate (HFR) has been specially developed with an isonatric mode maintaining an equal serum sodium concentration between start and end of the dialysis session, combined with ultrafiltration and conductivity profiles. We hypothesized that using this biofeedback in an isonatric mode would have a beneficial effect on blood pressure and dialysis tolerance. The study protocol has been approved by our ethics committee and is presented herein. PMID- 22322822 TI - Effect of mitofusin 2 overexpression on the proliferation and apoptosis of high glucose-induced rat glomerular mesangial cells. AB - BACKGROUND: Mitofusin 2 (Mfn2) regulates mitochondrial morphology and associated signaling pathways. However, the role of Mfn2 in kidney disease is not fully understood. The present study aimed to investigate the effects of Mfn2 overexpression on high-glucose-induced cell proliferation and apoptosis. Another objective was to explore the possible underlying signal transduction mechanisms in a rat glomerular mesangial cell (GMC) line. METHODS: After adenovirus-mediated Mfn2 gene transfection, Mfn2 expression was detected by real-time PCR. Time dependent concentration changes in Mfn2 and relevant proteins induced by high glucose were investigated to define the optimal time for research. The protein expression levels of Mfn2, proliferating cell nuclear antigen (PCNA), p-Akt, p ERK1/2 and Bcl-2 were examined on Western blots. Cell proliferation was detected by the CCK-8 method. Apoptosis was analyzed by flow cytometry. RESULTS: Mfn2 gene expression was successfully increased via adenovirus mediation. The correlation of Mfn2 expression with p-ERK1/2 and phosphorylated Akt was significant 48 hours after high-glucose stimulation. p-ERK1/2 was increased by high glucose, but was inhibited by overexpressed Mfn2. Changes in the PCNA and GMC proliferative level coincided with p-ERK1/2. Overexpressed Mfn2 significantly inhibited Akt phosphorylation and Bcl-2 expression. The apoptosis rate increased in the AdMfn2 group. CONCLUSIONS: Overexpressed Mfn2 could alleviate GMC proliferation and increase apoptosis. Subsequently, cellular quantity is maintained, which may contribute to reversing early diabetic nephropathy pathological changes. Mfn2 may perform its activities through the MAPK/ERK and PI3K/Akt signal pathways in correlation with proliferation and apoptosis. PMID- 22322823 TI - Why home hemodialysis? A systematic "marketing" analysis. AB - BACKGROUND: Home hemodialysis (HHD) has met with alternating fortunes. The present revival of interest is due to lower costs and more frequent/efficient treatments. HHD is underdeveloped, and a marketing approach may help in defining development strategies. The aim of this study was to systematically review the recent literature (2000-2010) according to a marketing approach, defining the potential of HHD according to the classical marketing items: market size, growth rate, profitability, trends, keys for success, needs for structures and distribution channels. METHODS: A Medline search was conducted for 2000-2010. The analysis took into account the recent trends in publication as a measure of interest, size and trends, while survival and costs were analyzed as keys for success. The issues of structures and distribution channels were arbitrarily considered as equivalent to the overall hemodialysis market. RESULTS: Interest in HHD is growing, as shown by the increasing number of published papers (9 in 2000, 52 in 2010); yet, clinical studies accounted for less than half of the papers. In the 138 clinical studies, quality of life (33 papers) and metabolism (16 papers) were the most studied topics. Survival and cost analyses were highly heterogeneous (the broad inclusion of nocturnal or quotidian dialysis has to be mentioned). Overall, survival was equal to, or better than, that for other modalities, including transplantation and peritoneal dialysis; costs compared favorably with hospital dialysis and were equivalent to those of peritoneal dialysis. CONCLUSION: The small "market" of HHD is increasing, with potential for further growth, the keys for success being equivalence or superiority of survival at equivalent or lower costs. PMID- 22322824 TI - Measuring asymmetric dimethylarginine (ADMA) in CKD: a comparison between enzyme linked immunosorbent assay and liquid chromatography-electrospray tandem mass spectrometry. AB - BACKGROUND: Asymmetric dimethylarginine (ADMA) is increasingly being investigated as a renal and cardiovascular risk factor in chronic kidney disease (CKD). We assessed the degree of agreement of an enzyme-linked immunosorbent assay (ELISA) of ADMA and the gold standard liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS). METHODS: ADMA was measured in an incident cohort of 126 stable CKD patients. Correlations between methods were studied by estimating the interclass Pearson coefficient (IPC), Lin's concordance correlation coefficient (CCC) and the maximum likelihood intraclass correlation coefficient (ICC). Limits of agreement (LOA) were estimated using the Bland-Altman method. RESULTS: ADMA values were normally distributed with means of 0.78 +/- 0.16 (ELISA) and 0.59 +/- 0.09 mol/L (LC-MS/MS). IPC was 0.69 (95% confidence interval [95% CI], 0.59 0.78). Overall CCC was 0.29 (95% CI, 0.23-0.37), with a difference in means of 0.19 mol/L (95% LOA, -0.043 to 0.43), delta slope of 0.577 and delta intercept of 0.14 (vs. perfect agreement line). Data were similar across categories of clinical characteristics. Mixed models provided an ICC of 0.58 (95% CI, 0.46 0.69). Bias was larger among patients with glomerular filtration rate (GFR) <30 ml/min. When values obtained from ELISA were corrected using the slope and intercept estimates from concordance analyses, the adjusted ICC improved to 0.67 (95% CI, 0.57-0.76), and bias modification by GFR levels canceled out. CONCLUSIONS: In CKD, ELISA overestimates ADMA concentration as compared with LC MS/MS. Appropriate calibration is needed when ADMA is measured by ELISA in CKD patients. PMID- 22322825 TI - Cerebrospinal fluid collection tubes: a critical issue for Alzheimer disease diagnosis. PMID- 22322826 TI - Characterization of a novel mouse monoclonal antibody, clone 1E8.33, highly specific for human procollagen 11A1, a tumor-associated stromal component. AB - A novel IgG1, kappa mouse monoclonal antibody (clone 1E8.33) to human procollagen 11A1 has been generated. This antibody is poorly mutated, essentially in germ line configuration; its complementarity determining regions (CDRs) are especially rich in tyrosine and serine residues. The epitope recognized is encompassed in the YNYGTMESYQTEAPR amino acid stretch within the variable region of human procollagen 11A1. Human procollagens 5A1 and 11A1 are very similar. However, this antibody does not cross-react with human procollagen 5A1. In human breast tumors, only the activated peritumoral myofibroblasts show a strong intracytoplasmic staining with this antibody. As procollagen 11A1 is overexpressed in the stroma of human tumors with desmoplastic reaction, this antibody represents a valuable tool for diagnostic purposes. PMID- 22322827 TI - Comparison of bacterial communities in the throat swabs from healthy subjects and pharyngitis patients by terminal restriction fragment length polymorphism. AB - Terminal restriction fragment length polymorphism (T-RFLP) analysis was applied to characterize bacterial flora present in the throats of healthy subjects and pharyngitis patients. The 16S rRNA genes of bacteria present in throat metagenome were amplified by PCR with 6-carboxy-fluorescein (6-FAM)-labeled universal forward primer (27 F) and a universal reverse primer (1513R). The 16S rDNAs were digested with restriction enzymes with 4-bp recognition sites (MspI or RsaI) and analyzed by using an automated DNA sequencer. T-RFLP patterns were numerically analyzed using computer programs. From analysis of the throat bacterial community, patterns derived from MspI and RsaI digested samples of healthy subjects and pharyngitis patients were grouped into different clusters, though RsaI digested samples showed some uncertainty. Pharyngitis throats generated an average species richness of 9 [+/-2.1 (SD)] and 10 (+/-2.9) for MspI and RsaI digests, respectively, whereas healthy throats generated 6.3 (+/-1.2) and 6.1 (+/ 1.5) in MspI and RsaI digests, respectively. These results suggest that samples from pharyngitis patients contain an unexpected diversity of causative bacteria. The pharyngitis throats were colonized with a rich diversity of bacterial species than that of healthy throats. Using T-RFLP, we are able to detect a model bacterium, Streptococcus pyogenes SF370, and T-RF patterns were consistent with the Streptococcal T-RFLP patterns. Our study indicates that T-RFLP analysis is useful for the assessment of diversity of throat bacterial flora and rapid comparison of the community structure between subjects with and without pharyngitis. PMID- 22322828 TI - A new bifunctional chitosanase enzyme from Streptomyces sp. and its application in production of antioxidant chitooligosaccharides. AB - Chitosanases produced by microbes and plants are getting attention to explore vastly available marine waste. Chitooligosaccharides and glucosamine can be produced using chitosanase enzyme and have applications in food, pharma and other industries. A potential microbial chitosanase source was found after isolation and screening of chitosan degrading microbes from garden soil. An isolate, designated as C6 produced chitosanase enzyme upon induction by chitosan substrates. Production of 6 U/ml of chitosanase enzyme was achieved from this isolate on chitosan minimal salt broth medium at 32 degrees C after 3 days of growth. The enzyme was able to hydrolyse both chitosan and cellulosic substrates. Enzymatic production of D -glucosamine and chitooligosaccharides were studied with various chitosan substrates using crude enzyme. The yield of glucosamine was found to be 40% after 2 h of reaction at 40 degrees C, and chitosan oligomers were produced having two to six polymerizations at 60 degrees C reaction temperature. The hydrolysates showed 50% antioxidant activity as compared to ascorbic acid. PMID- 22322829 TI - Efficient microbial conversion of L-tyrosine to L-DOPA by Brevundimonas sp. SGJ. AB - L-DOPA (3,4-dihydroxyphenyl-L-alanine), the most widely used drug for the treatment of Parkinson's disease, was produced in buffer using biomass of Brevundimonas sp. SGJ. The effects of enhancers, such as carrageenan, diatomaceous earth, and activated charcoal, on the L-DOPA production were evaluated to obtain the maximum yield. The optimal process conditions found were pH 8, 2 g l-1 cell mass, 2 g l-1 L-tyrosine, 0.04 g l-1 CuSO4, 0.02 g l-1 L ascorbic acid, 0.5 g l-1 carrageenan, and 40 degrees C temperature. In addition, repeated use of cells resulted in the highest yield of 3.81 g l-1 (95.2%) of L DOPA with utilization of 4 g l-1 L-tyrosine, and the highest tyrosinase activity (9,201 U mg-1) was observed at 18 h of incubation. Furthermore, the produced L DOPA was confirmed by high-performance thin-layer chromatography, high performance liquid chromatography, and gas chromatography-mass spectroscopy. Kinetic studies showed significant values of Y (p/s), Q (s), and q (s) after optimization of the process. Thus, Brevundimonas sp. SGJ could be an eventual new source for large-scale production of L-DOPA. PMID- 22322830 TI - Isolation of four isomers of C96 and crystallographic characterization of nanotubular D3d(3)-C96 and the somewhat flat-sided sphere C2(181)-C96. PMID- 22322831 TI - Cancer research performance in the European Union: a study of published output from 2000 to 2008. AB - AIMS AND BACKGROUND: Although several studies have assessed cancer research performance in individual European countries, comparisons of European Union (EU27) performance with countries of similar population size are not available. METHODS: We compared cancer research performance in 2000-2008 between EU27 and 11 countries with over 100 million inhabitants. Performance should not have been affected by the 2007-2009 recession. We examined 143 journals considered oncology journals by Journal Citation Reports, accessing them via Scopus. Publications were attributed to countries using a published counting procedure. RESULTS: For number of publications, the USA held a clear lead in 2006-2008 (yearly averages: 10,293 USA vs 9,962 EU27), whereas the EU27 held the lead previously. EU27 was also second to the USA for total impact factor. China markedly improved its cancer publications record over the period. Compared to the USA, EU27 and Japan, the other countries (all developing) had a poor publications record. CONCLUSIONS: Comparative cancer research spending data are not available. However from 2002 to 2007, gross domestic expenditure on research and development (UNESCO data) increased by 34% in North America, 161% in China and only 28% in EU27. Thus the European Union is lagging behind North America and may well be eclipsed by China in research and development spending in the near future. We suggest that these new findings should be considered by policymakers in Europe and other countries when developing policies for cancer control. PMID- 22322832 TI - Clinical activity and cardiac tolerability of non-pegylated liposomal doxorubicin in breast cancer: a synthetic review. AB - BACKGROUND: Anthracycline-containing regimens have demonstrated significant disease-free and overall survival benefits in the adjuvant setting and also provide palliative benefit in metastatic disease. . Over the past two decades, an increasing proportion of patients have been exposed to adjuvant anthracyclines with concomitant reduction in their use for palliation, as a result of concerns regarding efficacy and cumulative anthracycline-associated cardiotoxicity, as well as the availability of other systemic chemotherapeutic options. This report reflects the consensus view of a meeting of oncologists, pharmacologists and cardiologists held in Florence, Italy, on April 30, 2010. The objectives of the meeting were to review the role and limits of conventional anthracyclines in the treatment of breast cancer, to provide recommendations for the use of novel anthracycline formulations, such as non-pegylated liposomal doxorubicin (NPLD), and to identify potential future indications for NPLD that warrant further research. PMID- 22322833 TI - Delays in the diagnosis and treatment of non-small-cell lung cancer. AB - AIMS: To investigate patterns of delays among patients with non-small-cell lung cancer and to identify reasons for the delays. METHODS: This prospective study included 101 patients with non-small-cell lung carcinoma. Clinical files of the patients were analyzed and a questionnaire was created to obtain data. Several time intervals and delays were determined for each patient. The reasons for the delays were also evaluated. RESULTS: The mean time was 59.9 days for the application interval, 40.3 days for the referral interval, 16.4 days for the diagnostic interval, and 24.7 days for the treatment interval. The application interval was longer than 30 days (patient's delay) in 48 patients (48.5%). There was a doctor delay in 54 (53.5%) patients, a referral delay in 47 (46.5%) patients, a diagnostic delay in 37 (36.6%) patients, and a treatment delay in 57 (56.4%) patients. The mean total time was 119.6 days. Sixty-two patients (62.6%) had a total delay. The most common reason for patient's delay was neglect of symptoms by patients. A low index of suspicion for lung cancer was the most common cause for referral delay. The low performance of diagnostic tests was the frequent reason for diagnostic delay. CONCLUSIONS: Patient's and doctor's delays were a common problem among patients with non-small-cell lung cancer. The rate of doctor's delay was higher than that of patient's delay. Several efforts such as education of the physicians and people about lung cancer should be made to reduce these delays. PMID- 22322834 TI - A phase II trial of 5-fluorouracil, leucovorin and mitomycin C in patients with advanced gastric cancer. AB - AIMS AND BACKGROUND: Low-dose leucovorin is a well known potentiator of 5 fluorouracil activity in colorectal cancer but not in gastric cancer. To assess their efficacy on response rate and survival, 5-fluorouracil and low-dose leucovorin were combined with mitomycin C. METHODS: Fifty patients with gastric cancer and metastatic disease, unresectable or relapsed disease were treated with the following regimen every 28 days: mitomycin C, 7 mg/m2 IV bolus on day 1, and leucovorin, 20 mg/m2 IV, followed immediately by 5-fluorouracil, 375 mg/m2 on days 1-5. All had measurable disease and were assessable for toxicity. Prognostic factors were analyzed to examine any association with response rate or overall survival. RESULTS: Nineteen of the 48 assessable patients (39.6%; 95% confidence interval [CI], 25.8-53.4) responded, including 4 complete responses (8.3%). The median progression-free survival was 108 days (range, 18+ - 146), and the median duration of survival was 338 days (11.3 months; range, 18+ - 903 days). Response rate and overall survival were not significantly associated with CEA level, performance status, age, or primary and metastatic tumor sites. Toxicity associated with the chemotherapy was tolerable, and all patients were treated at the outpatient clinic. Leukopenia and thrombocytopenia WHO grade >=3 occurred in 5% and 1% of the patients, respectively. Nausea and vomiting were the most frequent adverse effects (29%), all grade 1 or 2. CONCLUSIONS: Combination chemotherapy of 5-fluorouracil plus leucovorin with mitomycin C is effective for the treatment of advanced gastric cancer and is well tolerated. PMID- 22322835 TI - The effect of neoadjuvant chemotherapy on hormone receptor status, HER2/neu and prolactin in breast cancer. AB - AIMS AND BACKGROUND: Histological and immunohistochemical findings may vary in cases of breast cancer. Possible changes in tumor markers between biopsies performed before and after neoadjuvant chemotherapy are controversial and pose a challenge when a clinical decision is needed. The objectives of the present study were: (i) to compare the immunohistochemical expression of estrogen, progesterone and prolactin receptors and HER-2/neu in breast cancer before and after neoadjuvant chemotherapy; and (ii) to correlate the expression of these tumor markers with partial tumor response to neoadjuvant chemotherapy. METHODS AND STUDY DESIGN: Immunohistochemical staining for breast tumor markers was performed in 90 cases of breast cancer. Statistical analysis was carried out using Fisher's exact test, McNemar's test, Spearman's correlation and the Kappa index with linear weighting (k). RESULTS: Agreement between markers before and after neoadjuvant chemotherapy was fair to moderate (k = 0.37-0.51). The immunohistochemical expression of HER-2/neu and prolactin receptors showed a significant, albeit weak correlation before and after neoadjuvant chemotherapy (HER-2/neu, rho = 0.34; P = 0.0009; k = 0.35 [95% CI, 0.19-0.51]). Prolactin status changed in 28/90 cases (P = 0.001; McNemar's test), whereas no changes were found in estrogen or progesterone receptors. No association was found between tumor marker expression and tumor response. CONCLUSIONS: It seems prudent to reevaluate immunohistochemical markers such as HER-2/neu after neoadjuvant chemotherapy, since the findings will guide the strategy for implementation of adjuvant systemic treatment. No correlation was found between the tumor markers analyzed in the present study and partial tumor response to neoadjuvant chemotherapy. PMID- 22322836 TI - Increased mean corpuscular volume of erythrocytes during capecitabine treatment: a simple surrogate marker for clinical response. AB - AIMS AND BACKGROUND: Capecitabine, as all fluoropyrimidines, interferes with vitamin metabolism and may thus have an impact on hematopoiesis. It is metabolized to its active form 5-fluoruracil by the enzyme thymidine phosphorylase, which exists in higher concentrations in tumor tissue and liver than in normal tissues. In the study, we investigated the changes in mean corpuscular volume (MCV) of red blood cells and the possible correlation of these changes with the clinical outcome of capecitabine treatment in women with metastatic breast cancer. METHODS AND STUDY DESIGN: Data from 75 metastatic breast cancer patients were analyzed retrospectively. Capecitabine was used at a dose of 2500 mg/m2 daily for 14 days of every 3-week period. Mean corpuscular volume of red blood cells and other parameters of complete blood count were recorded at the beginning of the treatment, in the ninth week, and periodically thereafter. RESULTS: Mean age was 51.5 +/- 10.8 and 61.3% of the patients were premenopausal. Capecitabine was administered as the median 3rd line (min-max: 1 9) treatment and a median of 6 cycles (min-max: 1-24) for metastatic breast cancer. Median DeltaMCV level (post-treatment values at ninth week - baseline) was 8. DeltaMCV was >=8 in 37 patients and <8 in 38 patients. The 35 of the 37 patients with DeltaMCV level >=8 and 25 of the 38 patients with DeltaMCV level <8 had clinical benefit (complete response + partial response + stable disease) from capecitabine treatment (P = 0.02). However, the difference between progression free survival of the patients with DeltaMCV levels higher than 8 and those with DeltaMCV levels lower than 8 according to Kaplan-Meier survival analysis was not statistically significant (6.7 and 4.3 months, respectively, P = 0.26). Additionally, median DeltaMCV level was 9.1 (min-max: -2.4 to 24.9) among patients who had clinical benefit and 5.90 (min-max: -0.8 to 12.3) among nonresponders (P = 0.016). CONCLUSIONS: Capecitabine increases the mean corpuscular volume levels of red blood cells by a yet unidentified mechanism. Early increment of mean corpuscular volume levels is higher than 8, i.e. by the 9th week, might predict clinical benefit from the treatment. PMID- 22322837 TI - Predictors of sensitivity to preoperative chemoradiotherapy of rectal adenocarcinoma. AB - OBJECTIVES: The purpose of the study was to identify predictive factors of tumor response to preoperative chemoradiotherapy for rectal adenocarcinoma. METHODS: Ninety-eight patients with nonmetastatic rectal adenocarcinoma received preoperative concurrent chemoradiotherapy and underwent mesorectal excision. After treatment, tumor response according to tumor regression grade were evaluated. The correlation of clinicopathologic factors to tumor response was analyzed. RESULTS: The results from a univariate analysis indicated that pretreatment carcinoembryonic antigen level <=3.0 ng/ml (P = 0.002), non-fixed tumor (P = 0.001), and tumor circumferential extent <=50% (P = 0.001) were associated significantly with a good tumor response. They also indicated that pretreatment positive lymph nodes (P = 0.032) were associated significantly with a poor tumor response. In multivariate analysis, the results indicated that pretreatment carcinoembryonic antigen level (hazard ratio, 2.930; P = 0.003), tumor mobility (hazard ratio, 2.651; P = 0.002) and circumferential extent of tumor (hazard ratio, 2.394; P = 0.019) independently predicted a good pathologic response rate. Pretreatment positive lymph nodes were not significantly associated with a good response (hazard ratio, 0.361; P = 0.191). CONCLUSIONS: Pretreatment carcinoembryonic antigen level, tumor mobility and circumferential extent of tumor may be helpful in predicting responsiveness in rectal adenocarcinoma to preoperative chemoradiotherapy, although the results should be confirmed in larger, more homogeneous studies. PMID- 22322838 TI - High-dose radiotherapy with intensity-modulated radiation therapy for advanced hepatocellular carcinoma. AB - AIMS AND BACKGROUND: We report the results of intensity-modulated radiotherapy for patients with advanced hepatocellular carcinoma who were not candidate for local ablative therapies, transarterial chemoembolization or hepatic arterial infusion chemotherapy. METHODS AND STUDY DESIGN: Between 2003 and 2008, 27 patients were treated with high-dose radiotherapy (median dose, 50.4 Gy). The equivalent sphere size of tumors was 11.4 +/- 2.6 cm. Nineteen and 8 patients were Child-Pugh class A and B, respectively. Eighteen patients had thromboses in large veins. Six patients were treated with radiotherapy as the initial treatment modality, and 21 patients received other treatments before radiotherapy. RESULTS: The overall response rate was 44.4% (1 pathologic complete response and 11 partial responses). The primary failure pattern was intrahepatic disease progression. Until the last follow-up, the primary liver masses and vein thromboses did not progress in 63.6% and 60.0% of the patients, respectively. The median progression-free survival and overall survival after radiotherapy rate were 3 and 5 months, respectively. Based on univariate analyses, response, Child Pugh classification, and vein thrombosis were significant factors for overall survival, and tumor response, tumor size, vein thrombosis, and multiplicity were significant factors for progression-free survival. Tumor response was the only significant prognostic factor for overall survival and progression-free survival based on multivariate analyses. CONCLUSIONS: Radiotherapy with intensity modulated radiotherapy achieved a good response rate in patients with advanced hepatocellular carcinoma, and patients who had a good response lived longer than patients who did not have a good response. PMID- 22322839 TI - Prevention of cutaneous damages induced by radiotherapy in breast cancer: an institutional experience. AB - BACKGROUND AND AIMS: A minimal part of patients treated with radiotherapy on the entire breast may present an acute, subacute or chronic cutaneous damage of the healthy tissues involved in the radiation fields. The aim of this retrospective study was to evaluate the most efficient topical hydrating treatment in the prevention of cutaneous radio-induced acute effects in breast cancer. MATERIAL AND METHODS: From February 2009 to March 2010, 100 patients affected by breast cancer have been recruited, all of the female sex and with an average age of 47 years. The following topical treatments were compared: Pure vitamin E (Vea lipogel(r)), Omega-3,6,9 (Quinovit(r)), Betaglucan, sodium hyaluronate (Neoviderm(r)), Vitis vinifera A.s-I-M.t-O.dij, (Ixoderm(r)), natural triglycerides-fitosterols (Xderit(r)). All enrolled patients were subjected to breast conservative treatment (quadrantectomy with or without homolateral axillary dissection) and without prosthesis positioning, in combination or not with hormonal treatment. Evaluation of the cutaneous acute toxicity was defined according to the RTOG scale either during radiotherapy and during follow-up (3 months after radiation treatment). RESULTS: All patients completed the radiotherapy; 62% of patients presented G0-G1 cutaneous toxicity, 28% have developed G2 cutaneous toxicity, 10% have developed G3 toxicity; no patient presented G4 toxicity. Analysis of the data revealed a correlation between the topical treatment used and the incidence of cutaneous toxicity. CONCLUSIONS: Of the patients who used the cutaneous hydrating creams--betaglucan, sodium hyaluronate (Neoviderm(r)) and Vitis vinifera A.s-I-M.t-O.dij (Ixoderm(r))- during the radiation treatment, 80% developed G0-G1 toxicity and 20% G2 toxicity. The patients who used the other hydrating creams tested in the study manifested not only G1-G2 toxicity but also some G3 toxicity. Chemotherapeutic treatment with taxanes and/or anthracyclines did not result in an increased breast cutaneous toxicity induced by radiotherapy. The hormone therapy given to patients undergoing radiotherapy did not result in increased breast cutaneous toxicity. Further analysis on a larger number of patients is necessary for definitive results. PMID- 22322840 TI - Circulating tumor cells as predictors of prognosis in metastatic breast cancer: clinical application outside a clinical trial. AB - AIMS AND BACKGROUND: Circulating tumor cells have a prognostic role in metastatic breast cancer. The aim of the study was to confirm the ability of circulating tumor cells, detected by the US Food and Drug Administration approved Cell Search assay, to predict the outcome of patients treated in a community general hospital. PATIENTS AND METHODS: A prospective mono-institutional study was conducted at the Department of Medical Oncology at Spedali Civili, Brescia, Italy, from January 2009 to September 2010. A total of 93 consecutive patients with metastatic breast cancer were enrolled. Patients underwent a blood sample collection to detect circulating tumor cells at baseline and, subsequently, at the first follow-up examination (after 3-4 weeks from the beginning of a systemic therapy). A third sample was drawn at disease progression (at the beginning of a subsequent new course of therapy). The prognostic cutoff value of circulating tumor cells was fixed at 5 cells/7.5 ml of blood. RESULTS: At baseline, median overall survival and progression-free survival in the subgroup >=5 circulating tumor cells/7.5 ml of blood were significantly shorter (5 months and 3 months, respectively) than in the subgroup with <5 circulating tumor cells (8 months and 7 months, respectively) (P = 0.003 and P <0.001). At the first follow-up, the subgroup with more than 5 circulating tumor cells/7.5 ml of blood had a median overall survival of 4 months versus 8 months in the subgroup with <5 circulating tumor cells (P <0.001) and a median progression-free survival of 3 months versus 7 months respectively (P <0.001). At multivariate analysis, the level of circulating tumor cells at the first follow-up and at baseline remained significant as a predictor of progression-free and overall survival. The number of metastatic sites was significantly associated with overall and progression free survival and correlated with the number of circulating tumor cells. CONCLUSIONS: Our study confirms the role of circulating tumor cells as predictors of prognosis in metastatic breast cancer patients treated in general clinical practice. PMID- 22322841 TI - Prognostic value of plasma D-dimer levels in lung carcinoma. AB - AIMS AND BACKGROUNDS: Plasma concentrations of several proteases of the coagulation system have been shown to predict prognosis in malignancy. The study was aimed to investigate the prognostic value of plasma D-dimer concentrations and some other coagulation factors in lung cancer. METHODS: Between 2004 and 2008, 100 newly diagnosed lung cancer patients and 25 healthy individuals serving as the control group were evaluated. The patients had no history of coagulation system disorders or anticoagulant therapy. Plasma D-dimer concentrations, prothrombin time, activated partial thromboplastin time, international normalized ratio and blood counts of the patients were obtained. Patient age, lung cancer stage, tumor histology, therapy modalities (surgery, chemotherapy and radiotherapy), therapy outcomes and survival durations of the patients were determined. RESULTS: The median age of the patients (86 males/14 females) was 67 years, and 15% had stage 2, 26% had stage 3A, 24% had stage 3B, and 35% had stage 4 disease. Histologic subtypes were non-small cell carcinoma (87%) and small cell carcinoma (13%). The median D-dimer level of the patients was 1250 ng/dl, which was significantly higher than that of the control group. Survival duration was significantly higher in patients with low D-dimer levels (P <0.05). D-dimer plasma levels predicted survival independently of the clinical stage of disease, histologic tumor type and performance status of the patient (HR = 5.1; 95% confidence interval, 1.015-1.19, P = 0.013). Plasma D-dimer level was significantly higher in metastatic disease (P <0.01). CONCLUSIONS: The results suggest that D-dimer plasma levels might be useful to predict the clinical outcome and survival of patients with lung cancer. PMID- 22322842 TI - Non-sentinel lymph node metastases in breast cancer patients with a positive sentinel lymph node: validation of five nomograms and development of a new predictive model. AB - AIMS AND BACKGROUND: Discordance of intraoperative analysis with definitive histology of the sentinel lymph node in breast cancer leads to completion axillary lymph node dissection, which only in 35-50% shows additional nodal metastases. The aim of the study was to identify individual patient risk for non sentinel lymph node metastases by validating several statistical methods present in the recent literature and by developing a new tool with the final goal of avoiding unnecessary completion axillary lymph node dissection. METHODS: We retrospectively evaluated 593 primary breast cancer patients. Completion axillary lymph node dissection was performed in 139 with a positive sentinel lymph node. The predictive accuracy of five published nomograms (MSKCC, Tenon, Cambridge, Stanford and Gur) was measured by the area under the receiver operating characteristic curve. We then developed a new logistic regression model to compare performance. Our model was validated by the leave-one-out cross validation method. RESULTS: In 53 cases (38%), we found at least one metastatic non-sentinel lymph node. All the selected nomograms showed values greater than the 0.70 threshold, and our model reported a value of 0.77 (confidence interval = 0.69-0.86 and error rate = 0.28) and 0.72 (confidence interval = 0.63-0.81, error rate = 0.28) after the validation. With a 5% cutoff value, sensitivity was 98% and specificity 9%, for a cutoff of 10%, 96% and 2%, respectively. CONCLUSIONS: All the nomograms were good discriminators, but the alternative developed model showed the best predictive accuracy in this Italian breast cancer sample. We still confirm that these models, very accurate in the institution of origin, require a new validation if used on other populations of patients. PMID- 22322843 TI - Overexpression of tyrosine kinase receptor B promotes metastasis of ovarian serous adenocarcinoma by lymphangiogenesis. AB - AIMS AND BACKGROUND: The aim of this study was to detect the expression features of tyrosine kinase receptor B (TrkB) and analyze the possible correlation between TrkB expression and lymph vessel density (LVD) in metastasis of ovarian serous adenocarcinoma. METHODS: An immunohistochemical method was used to evaluate TrkB expression in 139 ovarian tumor sections (103 primary ovarian serous adenocarcinomas and 36 serous adenomas) and investigate the correlation between TrkB expression and LVD, which was estimated by means of VEGFR-3 assessment. RESULTS: TrkB was significantly upregulated in serous adenocarcinomas and absent in serous adenomas. There was no association between TrkB expression and the histological grade of cancer cells. The expression of TrkB was correlated with surgicopathological stage and metastasis in serous adenocarcinomas. The level of TrkB was higher in advanced-stage than in early-stage disease. TrkB was overexpressed in metastatic lesions compared with the corresponding primary lesions. Furthermore, a positive correlation between TrkB expression and LVD in serous adenocarcinomas was observed. CONCLUSIONS: TrkB was overexpressed in ovarian serous adenocarcinomas and might be involved in cancer metastasis by associated lymphangiogenesis. PMID- 22322844 TI - Simultaneously targeting Bcl-2 and Akt pathways reverses resistance of nasopharyngeal carcinoma to TRAIL synergistically. AB - AIMS AND BACKGROUND: Despite progress in treatment techniques, the five-year survival rate of nasopharyngeal carcinoma (NPC) is disappointing. Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can selectively induce apoptosis in most tumor cells while sparing normal cells. Given the antiapoptotic functions of Bcl-2 and Akt, we examined the effects of targeting these pathways alone or simultaneously on TRAIL apoptosis in NPC cell lines. METHODS AND STUDY DESIGN: We first tested the cytotoxic effect of TRAIL and the expression of death receptors, Bcl-2, Akt, and p-Akt on four NPC cell lines by MTT and Western blotting, respectively. Small interfering RNAs (siRNAs) targeting Bcl-2 and PI3-K inhibitor (LY294002) were used alone or combined with TRAIL in the cell lines and cytotoxicity was examined by MTT. Apoptosis rates, mitochondrial transmembrane potential, and apoptotic pathway signals were detected by flow cytometric analysis, DiOC6(3) assays, and Western blotting after the various combination treatments on CNE-2, the cell line that was most resistant to TRAIL. RESULTS: Although no direct correlation between the sensitivity to TRAIL and the relative expression levels of Bcl-2 and activated Akt was found in the NPC cell lines examined, siRNA mediated the downregulation of Bcl-2 and LY294002-induced inactivation of Akt, increasing the sensitivity of all examined NPC cell lines to TRAIL. Synergistic enhancement of TRAIL-mediated cytotoxicity was observed in combination treatment of Bcl-2 siRNA and LY294002 compared to cells treated with each treatment alone. The synergistic effects were mediated through increased apoptotic signaling of the mitochondrial pathway, as was evident from the more increased mitochondrial depolarization, activation of caspase-9 and caspase-3, and suppression of XIAP. CONCLUSIONS: This study provides proof of principle that TRAIL combined with simultaneously targeting the Bcl-2 and Akt signaling pathways may have potential as a novel future treatment strategy for NPC. PMID- 22322845 TI - Dihydroartemisinin induces endoplasmic reticulum stress-mediated apoptosis in HepG2 human hepatoma cells. AB - AIMS AND BACKGROUND: Previous studies showed that dihydroartemisinin (DHA) possessed antitumor activity in many human tumor cells through the induction of apoptosis. The aim of this study was to investigate the effects of DHA on apoptosis in the human hepatocellular carcinoma cell line HepG2 and the possible molecular mechanisms involved. METHODS: The inhibitory effect of DHA on HepG2 cells was measured by MTT assay. The percentage of apoptotic cells was detected by flow cytometry with double staining of fluorescein isothiocyanate-annexin V/propidium iodide. The intracellular production of reactive oxygen species (ROS) and intracellular Ca2+ concentration ([Ca2+]i) were detected by fluorescence spectrophotometry. Protein expression of GADD153, Bcl-2 and Bax in HepG2 cells was examined by Western blot and immunocytochemistry. RESULTS: DHA significantly inhibited proliferation of HepG2 cells in a dose- and time-dependent manner. The apoptosis rates in HepG2 cells treated with 0, 50, 100 and 200 MUmol/L DHA for 24 hours were 2.53 +/- 0.88%, 24.85 +/- 3.63%, 35.27 +/- 5.92% and 48.53 +/- 7.76%, respectively. Compared with the control group, DHA significantly increased ROS generation and [Ca2+]i level (P <0.05), with the generation of ROS preceding the increase in [Ca2+]i. An increase in GADD153 and Bax expression and a decrease in Bcl-2 were observed in DHA-treated cells. Pretreatment with the antioxidant N acetylcysteine could attenuate the effects of DHA in the experiments. CONCLUSION: DHA could inhibit proliferation and induce apoptosis in HepG2 cell lines through increasing the intracellular production of ROS and [Ca2+]i. Endoplasmic reticulum stress-induced apoptosis may contribute to this effect by regulating the expression of GADD153, proapoptotic Bax, and antiapoptotic Bcl-2. PMID- 22322846 TI - Targeted inhibition of mammalian target of rapamycin (mTOR) signaling pathway inhibits proliferation and induces apoptosis of laryngeal carcinoma cells in vitro. AB - AIM AND OBJECTIVE: Laryngeal carcinoma is one of the most aggressive cancers of the head and neck region. The survival rate of patients with laryngeal carcinoma is low due to its late metastases and resistance to chemotherapy and radiotherapy. It was reported that mTOR was involved in the growth and apoptosis of various cancer cells. The aim of this study was to detect the effects of mTOR inhibition by mTOR shRNA on the proliferation, apoptosis and invasive ability of Hep-2 human laryngeal carcinoma cells in vitro. METHODS AND STUDY DESIGN: mTOR shRNA was designed and transfected into Hep-2 human laryngeal carcinoma cells. Untreated cells and cells treated with control vector (non-targeted shRNA) were used as control. The proliferation and apoptosis of Hep-2 cells were detected by MTT and flow cytometry. A transwell assay was used to measure the invasive ability of Hep-2. The inhibition effects on the mTOR signaling pathway by mTOR shRNA were studied using RT-PCR and Western blot. RESULTS: Our results showed that the mRNA and protein expression of mTOR and Akt were high in laryngeal carcinoma cells and could be inhibited by mTOR shRNA. At the same time, low expression of PTEN mRNA and protein was observed in Hep-2 cells. The expression increased when the cells were transfected with mTOR shRNA. This showed that mTOR shRNA could inhibit the proliferation and invasive ability of Hep-2 cells. It also could induce the apoptosis of Hep-2 cells in vitro. CONCLUSIONS: The mTOR signaling pathway plays an important role in the development of laryngeal carcinoma. The mTOR shRNA we designed in this experiment effectively inhibited the mTOR signaling pathway. It inhibited the proliferation and invasive ability of the studied laryngeal carcinoma cells and induced their apoptosis in vitro. mTOR might therefore be a useful target in the therapy of laryngeal carcinoma. PMID- 22322847 TI - Effect of endostatin on preventing postoperative progression of distant metastasis in a murine lung cancer model. AB - AIMS AND BACKGROUND: The relapse and metastasis of cancer remain a predominant cause of death after surgical removal of the primary tumor. There is a positive linkage between the postoperative upregulation of systemic angiogenic activity and distant tumor metastasis. In the present study, we established a spontaneous metastasis model and investigated whether antiangiogenic therapy using endostatin could prevent the progression of distant metastasis after removal of the primary tumor. METHODS: Female C57BL/6 mice were implanted subcutaneously with 1 * 106 Lewis lung cancer cells. Twenty days after implantation of the cancer cells, the primary tumor was removed and the mice were randomly divided into three groups. The NS group received normal saline, the L-ES group received 3 mg/kg endostatin, and the H-ES group received 20 mg/kg endostatin intravenously daily for 10 days. The effect of endostatin on lung metastases and the survival time of the mice were observed. Flow cytometry and immunohistochemistry were carried out to assess the angiogenic activity. The serum endostatin levels in peripheral blood were measured using an enzyme-linked immunosorbent assay. RESULTS: The mean number of metastatic pulmonary nodules and the mean net lung weight in the NS, L-ES and H ES groups was 10.2, 2.8 and 4.0, and 0.55 g, 0.31 g and 0.36 g, respectively. The difference between the NS group and the endostatin-treated groups was statistically significant (P <0.05). The endostatin-treated mice showed prolonged overall survival (P <0.05). Compared with the NS group, the endostatin-treated groups had lower levels of circulating endothelial cells in peripheral blood and showed a decrease in microvessel density in the metastatic tumors, with a more marked reduction in the L-ES group (P <0.05). The systemic presence of endostatin was gradually increased with the continued administration of endostatin to the mice. CONCLUSIONS: Antiangiogenic therapy with endostatin is effective in inhibiting the postoperative progression of distant metastasis. PMID- 22322848 TI - Colon perforation during sorafenib therapy for advanced hepatocelluar carcinoma. A case report. AB - There are no effective conventional systemic cytotoxic therapies for patients with unresectable or advanced hepatocellar carcinoma (HCC). Sorafenib, an oral multi-targeted tyrosine kinase inhibitor, was recently approved for the treatment of patients with HCC. Sorafenib is generally well tolerated and has an acceptable toxicity profile.Gastrointestinal perforation is a rare adverse event. We present a case of transverse colon perforation during sorafenib therapy for advanced HCC. A 68-year-old woman with advanced HCC was treated with sorafenib. Eight weeks later the patient presented with the sudden onset of sharp abdominal pain. Emergency surgery was performed for panperitonitis and a perforation involving the transverse colon. PMID- 22322849 TI - Obstructive colon metastases from lobular breast cancer: report of a case and review of the literature. AB - INTRODUCTION: Gastrointestinal metastases from breast cancer are rare. One large series reported a rate of 0.7% of gastrointestinal metastatic manifestations from breast cancer, but its true incidence could be underestimated. Here we report a case of bowel obstruction caused by sigmoid metastases from breast cancer and describe its relevance to histological origin and clinical practice. METHODS: The clinical course and histopathology of the case are reviewed and compared with reports of similar cases in the literature. RESULTS: An 80-year-old woman presented with bowel obstruction. Her medical history included infiltrating lobular breast cancer treated with left radical mastectomy 25 years before the current presentation; 13 years later bone metastases developed and were treated with hormone therapy. In 2003 the patient came to our emergency department because of symptoms of bowel obstruction. A computed tomography (CT) scan revealed a mass in the distal sigmoid causing the obstruction. A colostomy was performed, followed by a second operation completed with Hartmann's procedure. Histological examination revealed metastases from invasive lobular carcinoma. The patient was discharged 45 days postoperatively and died 9 months later because of disease progression. CONCLUSIONS: Although gastrointestinal metastases from breast cancer are rare, patients with diagnosed breast cancer, particularly invasive lobular carcinoma, should be regularly followed up with endoscopy, CT, endosonography and PET-CT when abdominal symptoms are present. This could permit early diagnosis of gastrointestinal metastases and improve treatment planning. PMID- 22322850 TI - Giant condyloma acuminatum of the anorectum: successful radical surgery with anal reconstruction. AB - Buschke-Lowenstein tumor, or giant condyloma acuminatum, is a relatively uncommon lesion of the anus with aggressive local invasive behavior which may present as a large warty tumor of the genital region with expansive and destructive growth. Many sporadic reports have been published suggesting various therapeutic strategies. We report a case of Buschke-Lowenstein tumor treated with conservative surgery followed by reconstructive procedures without a loop colostomy PMID- 22322851 TI - Bone marrow metastases from anaplastic oligodendroglioma presenting with pancytopenia and hypogammaglobulinemia: a case report. AB - We report the case of a 40-year-old man whose bone marrow metastases occurred 57 months after the initial diagnosis and 9 months after completing radiotherapy for an anaplastic oligodendroglioma. Four months before the demonstration of visceral metastases was obtained by bone marrow biopsy, the patient developed diffuse bone pain, pancytopenia, hypercalcemia, and panhypogammaglobulinemia. These abnormalities and other clinical signs of extracranial dissemination of the primary brain tumor were initially unrecognized until the patient was admitted with the suspicion of a nonsecretory multiple myeloma. We also briefly review the factors predisposing these tumors to spread outside the CNS, albeit rarely, and discuss the clinical implications of a misdiagnosis of extracranial invasion by anaplastic oligodendroglioma, whose chemosensitivity has been definitively demonstrated. PMID- 22322852 TI - Nipple adenoma arising in a supernumerary mammary gland: a case report. AB - Nipple adenoma, a benign tumour of the breast, is a relatively rare occurrence. This report describes an even rarer case of nipple adenoma arising within a supernumerary mammary gland. The presenting symptoms were a lump and throbbing pain in the axilla. Ultrasound scan and core biopsy proved inconclusive so surgical excision was undertaken, thus allowing a histological diagnosis. The patient made a full and uneventful recovery. Physicians must be aware that diseases of the breast and nipple-areola complex may also arise in accessory mammary tissue and accessory nipples should not be discounted as a common congenital anomaly. Instead they must be regarded, examined and treated as normal breast tissue. PMID- 22322853 TI - Curative resection of combined neuroendocrine carcinoma and adenocarcinoma of the gallbladder. AB - Neuroendocrine carcinoma of the gallbladder has very rarely been reported as it accounts for only 0.5% of all neuroendocrine tumors. It has a very aggressive biological behavior. These tumors are usually diagnosed at an advanced stage and surgical management is therefore not an option. We performed a hepatopancreaticoduodenectomy along with adjuvant chemotherapy in a 48-year-old patient with a neuroendocrine carcinoma of the gallbladder. The patient has been followed up at the outpatient clinic for 18 months without there having been any recurrence. Patients with a locally invasive neuroendocrine carcinoma in the gallbladder may benefit from aggressive surgical treatment followed by adjuvant chemotherapy. The primary management in high-grade metastatic tumors is, however, mainly medical. PMID- 22322854 TI - Role of radiotherapy in the treatment of fibrosarcoma of the spermatic cord: a case report and review of the literature. AB - BACKGROUND: Spermatic cord sarcomas are rare. The therapeutic approach is based only on case reports and small series. The standard treatment is radical orchiectomy with wide local resection, while the role of adjuvant therapies is not clear. We present a case of fibrosarcoma of the spermatic cord treated with surgery and adjuvant radiotherapy. A review of the literature about the role of adjuvant treatments is also discussed. CASE REPORT: A 59-year-old man presented a right testicular mass of about 4 * 3 cm in size. Biopsy showed a high-grade polymorphous sarcoma, consistent with a diagnosis of poorly differentiated fibromyosarcoma. He underwent a right radical inguinal orchiectomy and adjuvant radiotherapy (total dose: 5940 cGy). During treatment the patient developed a G3 skin toxicity (RTOG score) in the inguinal fold. After a follow-up of 57 months, he is alive and without evidence of local or distant recurrence. No late toxicity was noted. CONCLUSION: The optimal adjuvant management of spermatic cord sarcoma is still uncertain. Looking at the literature, it seems that adjuvant radiotherapy can improve locoregional control and disease-free survival without additional late toxicity. PMID- 22322855 TI - Accessory spleen mimicking a pancreatic neuroendocrine tumor. AB - A 60-year-old man underwent computed tomography as part of colorectal cancer follow-up. A hypervascular nodule was found within the pancreatic tail and subsequently proved to be positive on [111In] DTPA-octreotide scan. A neuroendocrine tumor of the pancreas was supposed and a distal pancreatectomy performed. Heterotopic splenic tissue was finally proved by pathological examination. The present case suggests that intrapancreatic accessory spleen be considered in the differential diagnosis of pancreatic lesions positive on [111In] DTPA-octreotide scan. PMID- 22322856 TI - The release of S-100B and NSE in severe traumatic head injury is associated with APOE epsilon4. AB - OBJECT: In this article we tested the hypothesis that the level of two biochemical markers of brain injury may be associated with the apolipoprotein E (APOE) epsilon4 allele. METHODS: In this prospective consecutive study patients with sTBI were included (n = 48). Inclusion criteria were Glasgow Coma Scale (GCS) score <= 8 at the time of intubation and sedation, patient age between 15 and 70 years, an initial cerebral perfusion pressure > 10 mmHg, and arrival to our level-one trauma university hospital within 24 h after trauma. Blood samples for neuron-specific enolase (NSE) and S-100B were collected as soon as possibly after arrival, and then twice daily (12-h intervals) for 5 consecutive days. Venous blood was used for APOE genotype determination. Clinical outcome at 3 months after injury was assessed with the Extended Glasgow Outcome Scale (GOSE). RESULTS: Significantly higher levels of the maximal S-100B (S-100B(max)) and area under the curve (S-100B(AUC)) were found in subjects with the APOE epsilon4 allele compared to those with non-epsilon4. A similar tendency was observed for NSE(max) and NSE(AUC), though not statistically significant. CONCLUSION: Our data indicate that there might be a gene-induced susceptibility to severe traumatic brain injury and that patients with the APOE epsilon4 allele may be more predisposed to brain cellular damage measured as S-100B and NSE. Thus, it seems to be of importance to consider the APOE genotype in interpreting the levels of the biomarkers. PMID- 22322857 TI - Identification of an acetylation-dependant Ku70/FLIP complex that regulates FLIP expression and HDAC inhibitor-induced apoptosis. AB - FLIP is a potential anti-cancer therapeutic target that inhibits apoptosis by blocking caspase 8 activation by death receptors. We report a novel interaction between FLIP and the DNA repair protein Ku70 that regulates FLIP protein stability by inhibiting its polyubiquitination. Furthermore, we found that the histone deacetylase (HDAC) inhibitor Vorinostat (SAHA) enhances the acetylation of Ku70, thereby disrupting the FLIP/Ku70 complex and triggering FLIP polyubiquitination and degradation by the proteasome. Using in vitro and in vivo colorectal cancer models, we further demonstrated that SAHA-induced apoptosis is dependant on FLIP downregulation and caspase 8 activation. In addition, an HDAC6 specific inhibitor Tubacin recapitulated the effects of SAHA, suggesting that HDAC6 is a key regulator of Ku70 acetylation and FLIP protein stability. Thus, HDAC inhibitors with anti-HDAC6 activity act as efficient post-transcriptional suppressors of FLIP expression and may, therefore, effectively act as 'FLIP inhibitors'. PMID- 22322858 TI - Type 2 transglutaminase is involved in the autophagy-dependent clearance of ubiquitinated proteins. AB - Eukaryotic cells are equipped with an efficient quality control system to selectively eliminate misfolded and damaged proteins, and organelles. Abnormal polypeptides that escape from proteasome-dependent degradation and aggregate in the cytosol can be transported via microtubules to inclusion bodies called 'aggresomes', where misfolded proteins are confined and degraded by autophagy. Here, we show that Type 2 transglutaminase (TG2) knockout mice display impaired autophagy and accumulate ubiquitinated protein aggregates upon starvation. Furthermore, p62-dependent peroxisome degradation is also impaired in the absence of TG2. We also demonstrate that, under cellular stressful conditions, TG2 physically interacts with p62 and they are localized in cytosolic protein aggregates, which are then recruited into autophagosomes, where TG2 is degraded. Interestingly, the enzyme's crosslinking activity is activated during autophagy and its inhibition leads to the accumulation of ubiquitinated proteins. Taken together, these data indicate that the TG2 transamidating activity has an important role in the assembly of protein aggregates, as well as in the clearance of damaged organelles by macroautophagy. PMID- 22322859 TI - Mutual antagonism of TGF-beta and Interleukin-2 in cell survival and lineage commitment of induced regulatory T cells. AB - Transforming growth factor beta (TGF-beta)- and Interleukin-2 (IL-2)-mediated signaling enables the generation and expansion of induced regulatory T (iTreg) cells that carry high hopes for the treatment of chronic inflammatory and autoimmune diseases. Knowledge about factors stabilizing their lineage commitment and lifespan, however, is limited. Here, we investigated the behavior of iTreg cells, derived from apoptosis-defective mouse mutants, during activated cell autonomous cell death, triggered by cytokine-deprivation, or activation-induced cell death (AICD) after restimulation of the T-cell receptor, and compared these responses with those of effector T cells. We observed that iTreg cells were much more sensitive to IL-2-deprivation but poorly susceptible to AICD. In fact, when apoptosis was compromised, T-cell receptor (TCR)-religation resulted in methylation-independent, ERK- and PI3K/mTOR-mediated loss of Foxp3 expression, impaired suppressive capacity and effector cytokine production. Although iTreg cells prevented colitis induction they rapidly lost Foxp3-GFP expression and gained ability to produce effector cytokines thereby imposing Th1 cell fate on resident effector cells. Surprisingly, iTreg cell conversion itself was limited by TGF-beta-mediated Bim/Bcl2L11-dependent apoptosis. Hence, the very same cytokine that drives the generation of iTreg cells can trigger their demise. Our results provide novel insights in iTreg cell biology that will assist optimization of iTreg-based therapy. PMID- 22322860 TI - Retinoblastoma tumor-suppressor protein phosphorylation and inactivation depend on direct interaction with Pin1. AB - Inactivation of the retinoblastoma protein (pRb) by phosphorylation triggers uncontrolled cell proliferation. Accordingly, activation of cyclin-dependent kinase (CDK)/cyclin complexes or downregulation of CDK inhibitors appears as a common event in human cancer. Here we show that Pin1 (protein interacting with NIMA (never in mitosis A)-1), a peptidylprolyl isomerase involved in the control of protein phosphorylation, is an essential mediator for inactivation of the pRb. Our results indicate that Pin1 controls cell proliferation by altering pRb phosphorylation without affecting CDK and protein phosphatase 1 and 2 activity. We demonstrated that Pin1 regulates tumor cell proliferation through direct interaction with the spacer domain of the pRb protein, and allows the interaction between CDK/cyclin complexes and pRb in mid/late G1. Phosphorylation of pRb Ser 608/612 is the crucial motif for Pin1 binding. We propose that Pin1 selectively boosts the switch from hypo- to hyper-phosphorylation of pRb in tumor cells. In addition, we demonstrate that the CDK pathway is responsible for the interaction of Pin1 and pRb. Prospectively, our findings therefore suggest that the synergism among CDK and Pin1 inhibitors holds great promise for targeted pharmacological treatment of cancer patients, with the possibility of reaching high effectiveness at tolerated doses. PMID- 22322861 TI - LIAD-fs scheme for studies of ultrafast laser interactions with gas phase biomolecules. AB - Laser induced acoustic desorption (LIAD) has been used for the first time to study the parent ion production and fragmentation mechanisms of a biological molecule in an intense femtosecond (fs) laser field. The photoacoustic shock wave generated in the analyte substrate (thin Ta foil) has been simulated using the hydrodynamic HYADES code, and the full LIAD process has been experimentally characterised as a function of the desorption UV-laser pulse parameters. Observed neutral plumes of densities >10(9) cm(-3) which are free from solvent or matrix contamination demonstrate the suitability and potential of the source for studying ultrafast dynamics in the gas phase using fs laser pulses. Results obtained with phenylalanine show that through manipulation of fundamental femtosecond laser parameters (such as pulse length, intensity and wavelength), energy deposition within the molecule can be controlled to allow enhancement of parent ion production or generation of characteristic fragmentation patterns. In particular by reducing the pulse length to a timescale equivalent to the fastest vibrational periods in the molecule, we demonstrate how fragmentation of the molecule can be minimised whilst maintaining a high ionisation efficiency. PMID- 22322862 TI - First-principles study of nanometer-sharp domain walls in ferromagnetic Fe monolayers under in-plane strain. AB - We investigated a nanometer-sharp magnetic domain wall (DW) structure in a free standing Fe(110) monolayer and studied the crucial role of in-plane strain using fully unconstrained noncollinear ab initio spin-density-functional theory calculations within the generalized gradient approximation. The DW width is calculated to be 0.86 nm. A precise vector-field description of the magnetization density revealed that a noncollinear character in the DW was spatially confined between atoms, whereas a collinear and high magnetization density was localized around each atom. In the rapid rotation of magnetic moments in the DW, we found an electron rearrangement from the d(zx) and d(x(2)-y(2)) states to the d(xy), d(yz) and d(z(2)) states due to a shift of band structures. Applied tensile and compressive in-plane strains both bring about narrower DWs in the monolayer except when the strain is small. The strain dependence of the DW width is discussed in terms of both exchange interaction and magnetocrystalline anisotropy. PMID- 22322863 TI - MiR-182 overexpression in tumourigenesis of high-grade serous ovarian carcinoma. AB - Molecular pathogenesis of high-grade serous ovarian carcinoma (HG-SOC) is poorly understood. Recent recognition of HG-SOC precursor lesions, defined as serous tubal intraepithelial carcinoma (STIC) in fimbria, provides a new venue for the study of early genetic changes in HG-SOC. Using microRNA profiling analysis, we found that miR-182 expression was significantly higher in STIC than in matched normal Fallopian tube. Further study revealed that miR-182 was significantly overexpressed in most HG-SOC cases. To test whether miR-182 plays a major role in early tumourigenesis of HG-SOC, we overexpressed miR-182 in immortalized ovarian surface, Fallopian tube secretory cells and malignant ovarian cell lines, and found that miR-182 overexpression resulted in increased tumour transformation in vitro, and enhanced tumour invasiveness in vitro and metastasis in vivo. Mechanistically, we demonstrated that the oncogenic properties of miR-182 in ovarian cancer were mediated in part by its impaired repair of DNA double-strand breaks and negative regulation of breast cancer 1 (BRCA1) and metastasis suppressor 1 (MTSS1) expression as well as its positive regulation of the oncogene high-mobility group AT-hook 2 (HMGA2). Our findings suggest that miR-182 dysregulation confers powerful oncogenic potential in the tumourigenesis of HG SOC. Copyright (c) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID- 22322864 TI - Introduction to SOE Special Issue. PMID- 22322865 TI - The devil is in the details: community based participatory research. PMID- 22322866 TI - Network for cancer control research in American Indians and Alaska Natives: a historical perspective. AB - In the past, cancer incidence and mortality for American Indian/Alaska Native populations have been suppressed in some publications based on small numbers and racial misclassification. Regional differences in cancer incidence and mortality in Native Americans have been observed as early as 1984. The cancer incidence, mortality, and survival data for American Indian/Alaska Native population have been better documented. Good stable models for the state tumor registries for cancer surveillance exist in the New Mexico and Alaska tumor registries. The Network for Cancer Control Research in American Indian/Alaska Natives was supported by the Special Populations branch of the National Cancer Institute. The Network formulated a plan for reducing cancer incidence and mortality in Native Americans and also to improve their survival. This Strategic Plan which proposed to educate federal agencies and state agencies about the increased incidence and mortality of cancer in American Indian/Alaska Natives also informed the Native American population of the specific risks of cancer in their communities. The Strategic Plan was published and implemented by the Network, and its goals have been continued by the Spirit of Eagles. PMID- 22322867 TI - The insect defensin lucifensin from Lucilia sericata. PMID- 22322868 TI - Aromatic aldols and 1,5-diketones as optimized fragrance photocages. AB - Aromatic aldols and 1,5-diketones with abstractable gamma-hydrogen atoms are highly photoactive cage molecules for the release of fragrance carbonyl compounds (aldehydes and Michael ketones, respectively). Aldols 3a-d are easily accessible by Mukaiyama addition and are cleaved to form the substrates with high quantum yields under solar radiation. By tuning the properties of the chromophores, a series of delta-damascone cages 5 were developed that can be used for selective and fast (5a,e) or slow (5b,d) release of fragrances under air and solar irradiation. The intermediates of the Norrish II process were observed by laser transient absorption spectroscopy. PMID- 22322869 TI - The combination of hyperthermia or chemotherapy with gimeracil for effective radiosensitization. AB - PURPOSE: 5-chloro-2,4-dihydroxypyridine (gimeracil) is a component of the oral fluoropyrimidine derivative S-1. Gimeracil was originally added to S-1 to yield prolonged 5-fluorouracil (5-FU) concentrations in serum and tumor tissues by inhibiting dihydropyrimidine dehydrogenase, which degrades 5-FU. We previously demonstrated that gimeracil enhances the efficacy of radiotherapy through the suppression of homologous recombination (HR) in DNA double strand repair. The goal of this paper was to examine the effects of gimeracil on the sensitivity of anticancer drugs and hyperthermia in order to obtain effective radiosensitization. MATERIALS AND METHODS: Various cell lines, including DLD 1 (human colon carcinoma cells) and cells deficient in HR or nonhomologous end joining (NHEJ), were used in clonogenic assays. The survival of these cells after various treatments (e.g., drug treatment, heat treatment, and radiation) was determined based on their colony-forming ability. RESULTS: Gimeracil enhanced cell-killing effects of camptothecin (CPT), 5-FU, and hydroxyurea. Gimeracil sensitized effects of CPT or 5-FU to cells deficient in HR or NHEJ to a similar extent as in other cells (DLD1 and a parent cell), indicating that its sensitizing mechanisms may be different from inhibition of HR or NHEJ. Combination of gimeracil and CPT or 5-FU sensitized radiation more effectively than each modality alone. Gimeracil also enhanced heat sensitivity at 42 degrees C or more. The degree of heat sensitization with gimeracil increased as the temperature increased, and the combination of gimeracil and heat-sensitized radiation was more effective than each modality alone. CONCLUSION: Gimeracil enhanced sensitivity of CPT, 5-FU, and hyperthermia. Combination of these modalities sensitized radiation more efficiently than each modality alone. PMID- 22322870 TI - Review of research on Dendrobium, a prized folk medicine. AB - Medicinal plants of the Dendrobium genus are highly prized, and hence, methodologies have been developed to authenticate Dendrobium drugs from its adulterants. Many bioactive constituents of Dendrobium species have been identified. The macromolecules included lectins; the enzymes chalcone synthase, sucrose synthase, and cytokinin oxidase; and polysaccharides. The polysaccharides display immunomodulatory and hepatoprotective activities. Alkaloids exhibit antioxidant, anticancer, and neuroprotective activities. Other compounds manifest antioxidant, anticancer, and immunomodulatory. PMID- 22322871 TI - Mitsuaria chitosanase with unrevealed important amino acid residues: characterization and enhanced production in Pichia pastoris. AB - A chitosan plate assay was employed to screen for chitosanase-producing bacterial strains and isolate 141 was found to exhibit high activity. Characterization of this isolate revealed that it belonged to Mitsuaria (designated as Mitsuaria sp. 141). The encoded chitosanase (choA) gene was then cloned by PCR and the deduced amino acid sequence showed 98% identity to a formerly described Mitsuaria chitosanitabida 3001 ChoA (McChoA). Surprisingly, the ChoA encoded by Mitsuaria sp. 141 (MsChoA) appeared to have a much higher optimum temperature compared to McChoA. Site-directed mutagenesis was then employed to generate five MschoA mutant genes encoding MsChoA K204Q, R216K, T222N, R216K/T222N, or K204Q/R216K/T222N. All the ChoA mutants exhibited a much lower specific activity and a lower optimum temperature. The results confirmed that the substitution of three non-conserved amino acids accounts for the major reduction of the enzyme activity in MsChoA. Furthermore, the MschoA gene was cloned for over-expression in Pichia pastoris after coding sequence optimization. One of the P. pastoris transformants with Mut(S) phenotype was found to produce 1,480.2 +/- 340.9 U ChoA mL(-1) of cell culture by high-cell-density fermentation. This represents the highest yield of recombinant ChoA production that has ever been reported thus far. The recombinant P. pastoris strain should therefore be well suited for industrial-scale production of chitosanase. PMID- 22322872 TI - Bioconversion of crude glycerol by fungi. AB - The production of synthetic glycerol from petrochemical feedstocks has been decreasing in recent years. This is largely due to increasing supplies of crude glycerol derived as a co-product from the oleochemical industry, especially biodiesel production. The price of glycerol is at historic lows, and the supply of crude glycerol is projected to grow faster than its industrial uses. This oversupply is driving the transition from glycerol as a product to glycerol as a precursor for new industrial applications, including its use as a substrate for bioconversion. This article reviews the use of fungi for the bioconversion of crude glycerol to the value-added products 1,2-propanediol, ethanol, single cell oil, specialty polyunsaturated fatty acids, biosurfactants, and organic acids. Information on the impurities of crude glycerol from different industrial processes is also included. PMID- 22322873 TI - A novel actinomycete derived from wheat heads degrades deoxynivalenol in the grain of wheat and barley affected by Fusarium head blight. AB - Deoxynivalenol (DON) is a hazardous and globally prevalent mycotoxin in cereals. It commonly accumulates in the grain of wheat, barley and other small grain cereals affected by Fusarium head blight (caused by several Fusarium species). The concept of reducing DON in naturally contaminated grain of wheat or barley using a DON-degrading bacterium is promising but has not been accomplished. In this study, we isolated a novel DON-utilising actinomycete, Marmoricola sp. strain MIM116, from wheat heads through a novel isolation procedure including an in situ plant enrichment step. Strain MIM116 had background degradation activity, and the activity was enhanced twofold by the consumption of DON. Among Tween 20, Triton X-100 and Tween 80, we selected Tween 80 as a spreading agent of strain MIM116 because it promoted DON degradation and the growth of strain MIM116 in the presence of DON. The inoculation of MIM116 cell suspension plus 0.01% Tween 80 into 1,000 harvested kernels of wheat and barley resulted in a DON decrease from approximately 3 mg kg(-1) to less than 1 mg kg(-1) of dry kernels, even when cells had only basal levels of DON-degrading activity. To the best of our knowledge, this is the first report that describes (1) the isolation of a DON degrading bacterium from wheat heads, (2) the effects of surfactants on the biodegradation of DON and (3) the decrease of DON levels in naturally contaminated wheat and barley grain using a DON-degrading bacterium. PMID- 22322875 TI - Genetic association of short sleep duration with hypertension incidence--a 6-year follow-up in the Korean genome and epidemiology study. AB - BACKGROUND: Hypertension (HT) is caused by complex interactions between genetic and environmental factors. Despite evidence for an association between short sleep duration and the development of HT, genetic factors associated with this effect have not been defined. Here we prospectively investigated the incidence of HT in subjects with short sleep duration over a 6-year follow-up period, and identified associated genetic variants in a genome-wide association study. METHODS AND RESULTS: Sleep duration was determined by questionnaire and 3 categories were established: <5h, 5-7h, and >7h. Genotyping was carried out using the Affymetrix Genome-Wide Human Single Nucleotide Polymorphism (SNP) Array 5.0. Of the 4,965 individuals included in our study, 1,071 (543 of 2,330 men, 528 of 2,635 women) developed HT. The cumulative incidence of HT during the 6-year study period was 21.6%. Sleep duration <5h was associated with an increased risk of incident HT only in premenopausal women (adjusted hazard ratio 2.43, 95% confidence interval 1.36-4.35). The SNPs of rs6691577, rs2226284 and rs12756253 were associated with this increased risk. CONCLUSIONS: This prospective communitywide study showed that premenopausal women with short sleep duration had an increased risk of incident HT, and found associations with specific genomic markers. PMID- 22322874 TI - "Hypothesis for the modern RNA world": a pervasive non-coding RNA-based genetic regulation is a prerequisite for the emergence of multicellular complexity. AB - The transitions to multicellularity mark the most pivotal and distinctive events in life's history on Earth. Although several transitions to "simple" multicellularity (SM) have been recorded in both bacterial and eukaryotic clades, transitions to complex multicellularity (CM) have only happened a few times in eukaryotes. A large number of cell types (associated with large body size), increased energy consumption per gene expressed, and an increment of non-protein coding DNA positively correlate with CM. These three factors can indeed be understood as the causes and consequences of the regulation of gene expression. Here, we discuss how a vast expansion of non-protein-coding RNA (ncRNAs) regulators rather than large numbers of novel protein regulators can easily contribute to the emergence of CM. We also propose that the evolutionary advantage of RNA-based gene regulation derives from the robustness of the RNA structure that makes it easy to combine genetic drift with functional exploration. We describe a model which aims to explain how the evolutionary dynamic of ncRNAs becomes dominated by the accessibility of advantageous mutations to innovate regulation in complex multicellular organisms. The information and models discussed here outline the hypothesis that pervasive ncRNA based regulatory systems, only capable of being expanded and explored in higher eukaryotes, are prerequisite to complex multicellularity. Thereby, regulatory RNA molecules in Eukarya have allowed intensification of morphological complexity by stabilizing critical phenotypes and controlling developmental precision. Although the origin of RNA on early Earth is still controversial, it is becoming clear that once RNA emerged into a protocellular system, its relevance within the evolution of biological systems has been greater than we previously thought. PMID- 22322876 TI - Effects of H2S on myogenic responses in rat cerebral arterioles. AB - BACKGROUND: The potential biological significance of hydrogen sulfide (H2S) has attracted growing interests in recent years, but its role in the myogenic response of rat cerebral arterioles has not been explored. METHODS AND RESULTS: Rats were injected with NaHS (an H2S donor, 2-200 umol.kg-1.day-1, i.p.) or saline for 3 weeks. MBP was measured with a tail-cuff method. Cerebral arterioles were isolated and cannulated in an organ bath system, and vessel diameters were measured with an image-shearing device. Changes in diameter in response to stepwise increases in intravascular pressure (20-120 mmHg) were investigated under no-flow conditions. After the treatments, plasma H2S increased and MBP decreased significantly. NaHS reduced the myogenic response in a dose-dependent manner. This effect was markedly attenuated by glibenclamide, a K(ATP) channel blocker. Blockade of nitric oxide (NO) production with NG-nitro-L-arginine methyl ester (L-NAME, a NO synthase inhibitor) enhanced, whereas removal of the endothelium abolished the inhibitory role of NaHS on the myogenic response. CONCLUSIONS: For the first time it has been demonstrated that H2S decreases the myogenic response of cerebral arterioles in vivo, and this effect is endothelium dependent and partially mediated by K(ATP) channels. PMID- 22322877 TI - Chromosome 9p21 single nucleotide polymorphisms are not associated with recurrent myocardial infarction in patients with established coronary artery disease. AB - BACKGROUND: Chromosome 9p21 single nucleotide polymorphisms (SNPs) have been shown to be associated with coronary heart disease in multiple studies. The aim of the present study was to identify whether these SNPs are associated with recurrent myocardial infarction (MI), revascularization, or death in acute coronary syndrome (ACS) patients or in those undergoing coronary artery bypass grafting (CABG). METHODS AND RESULTS: TexGen registry participants with ACS (n=2,067) or CABG (n=1,176) were evaluated, to assess whether 9p21 SNPs (rs1333049, rs2383206, rs10757278, rs10757274) were associated with recurrent MI (primary outcome), recurrent revascularization, or death (secondary outcomes) at approximately 3.2 years of follow-up. Carriers of risk allele (C) for rs1333049 presented at an earlier age (62 vs. 63.5 years in non-carriers, P=0.0004) with more extensive disease (number of vessels with significant stenosis: 1.9 vs. 1.7 in non-carriers, P=0.001) in the ACS group. In adjusted models, the C allele was not associated with recurrent MI (hazard ratio [HR], 1.01; 95% confidence interval [CI]: 0.74-1.38), recurrent revascularization (HR, 0.98; 95%CI: 0.78 1.23), or death (HR, 0.91; 95%CI: 0.69-1.18) in the ACS or CABG groups (recurrent MI: HR, 0.64; 95%CI: 0.40-1.05; recurrent revascularization: HR, 0.98; 95%CI: 0.61-1.55; death: HR, 0.89; 95%CI: 0.61-1.30). Results were similar for the other 3 SNPs. CONCLUSIONS: 9p21 SNPs were not associated with recurrent MI, revascularization, or mortality after ACS or CABG. Individuals with the rs1333049 C allele, however, may present with earlier and more extensive disease. PMID- 22322878 TI - Overshoot phenomena of respiratory gas variables during exercise recovery in cardiac patients. AB - BACKGROUND: Transient increases (overshoot) in respiratory gas variables have been observed during exercise recovery, but their clinical significance is not clearly understood. Our group evaluated the relationship between the presence of overshoot of respiratory gas variables and the parameters obtained from cardiopulmonary exercise testing (CPX). METHODS AND RESULTS: In total, 227 patients with various cardiac diseases underwent CPX. The overshoot phenomena of O2 uptake (.VO2), .VO2/heart rate (O2-pulse), and CO2 output (.VCO2) were analyzed by respiratory gas analysis during recovery after maximal exercise. The overshoot of .VO2, O2-pulse, and .VCO2 were recognized in 11 (5%), 43 (19%), and 12 (5%) patients, respectively. Compared with the patients without a .VO2 overshoot, those with a .VO2 overshoot had a significantly lower peak .VO2 (12.3+/-3.7 vs. 17.9+/-6.2ml.min-1.kg-1, P=0.003), lower anaerobic threshold (9.4+/-1.7 vs. 12.4+/-3.3 ml.min-1.kg-1, P=0.001), higher .VE-.VCO2 slope (38.0+/ 5.2 vs. 33.2+/-9.6, P=0.013), and lower left ventricular ejection fraction (LVEF) (39.9+/-22.8 vs. 55.8+/-16.8%, P=0.003). Similar findings were obtained for the patients with an O2-pulse overshoot and those with a .VCO2 overshoot. CONCLUSIONS: The overshoot phenomena of respiratory gas variables during recovery after maximal exercise are correlated with impaired cardiopulmonary function during exercise in cardiac patients. PMID- 22322880 TI - Seminal plasma metals concentration with respect to semen quality. AB - The aim of the current study was to assess relationships between multiple metals burden in human seminal plasma and semen quality parameters. Levels of five metals (lead, manganese, copper, arsenic, and selenium) in human seminal plasma were determined by inductively coupled plasma mass spectrometry (ICP-MS), and the correlations between the metal concentrations and semen parameters (sperm concentration, sperm motility rate, and sperm morphology) were analyzed. The activities of acid phosphatase (ACP) and of alpha-glucosidase in human seminal plasma were also determined. Of the 100 subjects, 21 had fertility problems according to the World Health Organization criteria and were designated as "abnormal group." Significant inverse correlations were found between the concentrations of Cu, As, Pb, and the sperm concentrations (r (Cu) = -0.312, P (Cu) = 0.029; r (As) = -0.328, P (As) = 0.021; r (Pb) = -0.377, P (Pb) = 0.008). Moreover, the Cu, Mn, and Se concentrations were significantly higher in the abnormal group than that in the normal group (P (Cu) = 0.024, P (Mn) = 0.002, P (Se) = 0.002). The ACP activity was significantly higher in the normal group than that in the abnormal group (P = 0.021). We also found a significantly negative correlation between alpha-glucosidase activity and the levels of As (r = -0.367, P = 0.023). These findings provide evidence for relationships between human semen quality and metal exposures. These relationships are consistent with animal data, but additional human and mechanistic studies are needed. PMID- 22322881 TI - The correlation between smoking status of family members and concentrations of toxic trace elements in the hair of children. AB - Hair analysis is a promising tool for routine clinical screening and diagnosis of heavy metal exposure and essential trace element status in the human body. Systemic intoxications have been identified by anomalously high values of toxins in hair samples. The aim of the present study is to evaluate the relationship between smoking habit of the family members and the levels of toxic and nontoxic trace elements in hair samples of children. The randomized cross-sectional controlled study comprised of 95 children (41 girls and 54 boys) between the ages of 1 and 6 years. After written informed consent was obtained, a face-to-face interview was conducted with the families about educational background, total income of the family, and smoking habits of family members. The mineral elements considered in this study were Zn, Se, B, V, Co, Mo, Mn, iron (Fe), Be, aluminum (Al), As, cadmium (Cd), lead (Pb), Hg, chromium (Cr), Ag, Be, nickel (Ni), copper (Cu), Sn, and antimony (Sb). Hair mineral contents were measured by inductively coupled plasma-mass spectrometry. The results showed that the levels of Cd, Pb, Cr, Sb, Fe, and Al in hair samples of children whose parents smoked were significantly higher than those whose parents were nonsmokers. The number of smokers and the frequency of smoking at home were positively correlated with Pb, Cd, Cu, Ni, and Sb levels found. At the same time, it was found that there was no correlation between toxic element concentrations and family income or educational background excluding the levels of Cd. A correlation was observed between the smoking status of family members and levels of toxic trace elements in hair where this correlation was more significant with the levels of Pb and Cd. High socioeconomic status and the level of education of family members did not have any effect on toxic trace levels in hair samples of children. PMID- 22322882 TI - Enhanced anti-diabetic activity of a combination of chromium(III) malate complex and propolis and its acute oral toxicity evaluation. AB - In order to obtain the additional benefit of anti-diabetic activity and protective effects of liver injury for diabetes, the anti-diabetic effect and acute oral toxicity of a combination of chromium(III) malate complex (Cr(2)(LMA)(3)) and propolis were assessed. The anti-diabetic activity of the combination of the Cr(2)LMA(3) and propolis was compared with Cr(2)(LMA)(3) and propolis alone in alloxan-induced diabetic mice by daily oral gavage for a period of 2 weeks. Acute oral toxicity of the combination of the Cr(2)LMA(3) and propolis was tested using ICR mice at the dose of 1.0-5.0 g/kg body mass by a single oral gavage and observed for a period of 2 weeks. The results of the anti diabetic activity of the combination from the aspects of blood glucose level, liver glycogen level, and the activities of aspartate transaminase, alanine transaminase, and alkaline phosphatase indicated that the increased anti-diabetic activity and the protective efficacy of liver injury for diabetes were observed. In acute toxicity study, LD(50) (median lethal dose) value for the combination was greater than 5.0 g/kg body mass. The combination of Cr(2)LMA(3) and propolis might represent the nutritional supplement with potential therapeutic value to control blood glucose and exhibit protective efficacy of liver injury for diabetes and non-toxicity in acute toxicity. PMID- 22322883 TI - Disulfiram, an old drug with new potential therapeutic uses for human hematological malignancies. AB - Disulfiram (DSF) is an aldehyde dehydrogenase inhibitor currently used for the treatment of alcoholism. Here, we show that multiple myeloma (MM) cell lines and primary cells from newly diagnosed and relapsed/resistant patients affected by MM, acute myeloid and lymphoblastic leukemia are significantly sensitive to DSF alone and in combination with copper. These effects are present at doses lower than those achievable in vivo after DSF standard administration. The cytotoxic effect achieved by this treatment is comparable to that obtained by conventional chemotherapy and is absent in normal hematopoietic cells. In addition, we found that DSF plus copper induces loss of mitochondrial membrane potential, triggers reactive oxygen species (ROS) production and activates executioner caspases. DSF copper-induced apoptosis and caspases activation are strongly reversed by antioxidant N-acetylcysteine, thus indicating a critical role of ROS. These results might suggest the use of the old drug DSF, alone or in combination with copper, in the treatment of hematological malignancies. PMID- 22322884 TI - Pathway simulations in common oncogenic drivers of leukemic and rhabdomyosarcoma cells: a systems biology approach. AB - A part of current research has intensively been focused on the proliferation and metabolic processes governing biological systems. Since the advent of high throughput methodologies such as microarrays, the load of genomic data has increased geometrically and along with that the need for computational methods to interpret these data. In the present study, we investigated in vitro the common proliferation and metabolic processes, associated with common oncogenic pathways, as far as gene expression is concerned, between the T-cell acute lymphoblastic leukemia (CCRF-CEM) and the rhabdomyosarcoma (TE-671) cell lines. We present a computational approach, using cDNA microarrays, in order to identify commonalities between diverse biological systems. Our analysis predicted that JAK1, STAT1, PIAS2 and CDK4 are the driving forces in the two cell lines. This type of analysis may lead to the understanding of the common mechanisms that transform physiological cells to malignant, and may reveal a new holistic approach to understanding the dynamics of tumor onset as well as the mechanistics behind oncogenic drivers. PMID- 22322885 TI - A fatty acid-binding protein 7/RXRbeta pathway enhances survival and proliferation in triple-negative breast cancer. AB - FABP7 has been implicated in tumour cell proliferation, cell migration, and poor prognosis in patients with high-grade astrocytoma and melanoma. In this study, we examine FABP7 expression in a cohort of 176 primary breast cancers by gene profiling and tissue microarray immunostaining. We show that FABP7 is significantly up-regulated in triple-negative breast cancer. Elevated FABP7 levels are associated with poor prognosis, absence of oestrogen and progesterone hormone receptors (ER, PR) and HER2, increased cell proliferation, and high tumour grade. Depletion of FABP7 in the ER/PR-negative cell line, MDA-MB-435S, significantly reduced cell growth rate and sensitized the cells to growth inhibition by omega-3 docosahexaenoic acid (DHA). A target of DHA-bound FABP7 in the nucleus is RXRbeta, a retinoid-activated nuclear receptor that functions as a transcription factor by either homodimerizing or heterodimerizing with other nuclear receptors such as PPARs. Based on our microarray data, RXRbeta, like FABP7, is an adverse prognostic factor for breast cancer. We propose that the DHA FABP7-RXRbeta pathway promotes cell survival/proliferation in triple-negative breast cancer. Targeting this pathway may thus provide an alternate route for the treatment of triple-negative breast cancer. PMID- 22322886 TI - Germ cell DNA-repair systems-possible tools in cancer research? AB - A major dogma in cancer research is that cancer begins at the cellular level. Because of this single-cell origin, evolutionary principles have often been used to explain how somatic cancer cells are selected at a sub-individual level. The traditional application of Darwinian theory, however, in which the colony of cells constituting an individual is regarded as a whole, has not been applied extensively to the understanding of cancer until recently. Two proponents for this view, Breivik and Gaudernack, have suggested that in certain situations the cost of DNA repair might exceed the cost of errors. This model predicts that genetic stability is configured for an optimal cost-benefit relationship. Natural selection is not expected to have produced the best genetic stability available in the human body, merely the best compromise of DNA repair and costs. Repair and maintenance of the vast human genome is thermodynamically expensive, and an optimal balance between DNA repair and dietary needs is likely to have originated. Furthermore, fast growth conveys significant advantages such as early maturation or cognitive development, but usually at the expense of replication accuracy. Thus, a compromise between growth speed and cancer risk is likely to have taken place. These and other ecological mechanisms have probably prevented genomic stability to reach its full potential in the human body. In contrast, germ lines express near perfect DNA maintenance. Although germ cells are specialized DNA-conserving cells with few other functions, it's not given that their proteins will all be incompatible with the somatic cell. One approach to study this would be to systematically explore which DNA-stability and -repair systems are unique in germ cells, and induce their expression in invertebrate and mammalian model organisms. This could unveil which DNA-repair systems are switched off in the somatic cell lines, as they are incompatible, and which are absent due to evolution. The present review discuss different DNA-repair systems and cell cycle check point control mechanisms shown to be different or unique in the germ cell, and how they may be utilized in cancer therapy. PMID- 22322887 TI - Emotion appraisal and the tryptophan hydroxylase 2 (TPH2) gene. AB - The purpose of this study was to investigate the association between the G-703T polymorphism of the tryptophan hydroxylase 2 (TPH2) gene (rs4570625) and emotion appraisal in healthy volunteers. Participants were asked to recall a situation characterized by a strong emotion and to rate appraisal processes: novelty/expectation, pleasantness, goal-conduciveness, fairness, responsibility/causation, coping ability, morality, and relationship to self concept. Results revealed that in the case of fear- and sadness-related autobiographical memories, participants with the GG genotype achieved higher appraisal scores for goal-conduciveness and lower scores for coping ability compared with participants with the TT genotype. In the case of joy, no differences were observed across genotypes. These results suggest that the TPH2 polymorphism affects appraisal processes in the case of negative emotions. PMID- 22322888 TI - Cationic rhodium(I)-catalyzed regioselective tandem heterocyclization/[3+2] cycloaddition of 2-(1-alkynyl)-2-alken-1-ones with alkynes. PMID- 22322889 TI - Dissociation dynamics of fluorinated ethene cations: from time bombs on a molecular level to double-regime dissociators. AB - The dissociative photoionization mechanism of internal energy selected C(2)H(3)F(+), 1,1-C(2)H(2)F(2)(+), C(2)HF(3)(+) and C(2)F(4)(+) cations has been studied in the 13-20 eV photon energy range using imaging photoelectron photoion coincidence spectroscopy. Five predominant channels have been found; HF loss, statistical and non-statistical F loss, cleavage of the C-C bond post H or F-atom migration, and cleavage of the C=C bond. By modelling the breakdown diagrams and ion time-of-flight distributions using statistical theory, experimental 0 K appearance energies, E(0), of the daughter ions have been determined. Both C(2)H(3)F(+) and 1,1-C(2)H(2)F(2)(+) are veritable time bombs with respect to dissociation via HF loss, where slow dissociation over a reverse barrier is followed by an explosion with large kinetic energy release. The first dissociative ionization pathway for C(2)HF(3) and C(2)F(4) involves an atom migration across the C=C bond, giving CF-CHF(2)(+) and CF-CF(3)(+), respectively, which then dissociate to form CHF(2)(+), CF(+) and CF(3)(+). The nature of the F loss pathway has been found to be bimodal for C(2)H(3)F and 1,1-C(2)H(2)F(2), switching from statistical to non-statistical behaviour as the photon energy increases. The dissociative ionization of C(2)F(4) is found to be comprised of two regimes. At low internal energies, CF(+), CF(3)(+) and CF(2)(+) are formed in statistical processes. At high internal energies, a long-lived excited electronic state is formed, which loses an F atom in a non-statistical process and undergoes statistical redistribution of energy among the nuclear degrees of freedom. This is followed by a subsequent dissociation. In other words only the ground electronic state phase space stays inaccessible. The accurate E(0) of CF(3)(+) and CF(+) formation from C(2)F(4) together with the now well established Delta(f)H(o) of C(2)F(4) yield self-consistent enthalpies of formation for the CF(3), CF, CF(3)(+) and CF(+) species. PMID- 22322890 TI - Overexpression of sigma-1 receptor inhibits ADAM10 and ADAM17 mediated shedding in vitro. AB - The sigma-1 receptor is a molecular chaperone protein highly enriched in the brain. Recent studies linked it to many diseases, such as drug addition, Alzheimer's disease, stroke, depression, and even cancer. Sigma-1 receptor is enriched in lipid rafts, which are membrane microdomains essential in signaling processes. One of those signaling processes is ADAM17- and ADAM10-dependent ectodomain shedding. By using an alkaline phosphatase tagged substrate reporter system, we have shown that ADAM10-dependent BTC shedding was very sensitive to both membrane lipid component change and sigma-1 receptor agonist DHEAS treatment while ADAM17-dependent HB-EGF shedding was not; and overexpression of sigma-1 receptor diminished ADAM17- and ADAM10-dependent shedding. Our results indicate that sigma-1 receptor plays an important role in modifying the function of transmembrane proteases. PMID- 22322891 TI - Effect of the antitumoral alkylating agent 3-bromopyruvate on mitochondrial respiration: role of mitochondrially bound hexokinase. AB - The alkylating agent 3-Bromopyruvate (3-BrPA) has been used as an anti-tumoral drug due to its anti-proliferative property in hepatomas cells. This propriety is believed to disturb glycolysis and respiration, which leads to a decreased rate of ATP synthesis. In this study, we evaluated the effects of the alkylating agent 3-BrPA on the respiratory states and the metabolic steps of the mitochondria of mice liver, brain and in human hepatocarcinoma cell line HepG2. The mitochondrial membrane potential (DeltaPsi(m)), O(2) consumption and dehydrogenase activities were rapidly dissipated/or inhibited by 3-BrPA in respiration medium containing ADP and succinate as respiratory substrate. 3-BrPA inhibition was reverted by reduced glutathione (GSH). Respiration induced by yeast soluble hexokinase (HK) was rapidly inhibited by 3-BrPA. Similar results were observed using mice brain mitochondria that present HK naturally bound to the outer mitochondrial membrane. When the adenine nucleotide transporter (ANT) was blocked by the carboxyatractiloside, the 3-BrPA effect was significantly delayed. In permeabilized human hepatoma HepG2 cells that present HK type II bound to mitochondria (mt-HK II), the inhibiting effect occurred faster when the endogenous HK activity was activated by 2-deoxyglucose (2-DOG). Inhibition of mt HK II by glucose-6-phosphate retards the mitochondria to react with 3-BrPA. The HK activities recovered in HepG2 cells treated or not with 3-BrPA were practically the same. These results suggest that mitochondrially bound HK supporting the ADP/ATP exchange activity levels facilitates the 3-BrPA inhibition reaction in tumors mitochondria by a proton motive force-dependent dynamic equilibrium between sensitive and less sensitive SDH in the electron transport system. PMID- 22322892 TI - Experimental results using 3-bromopyruvate in mesothelioma: in vitro and in vivo studies. AB - Over many years we have taken advantage of the special metabolism of cancer cells involving an increased consumption of glucose associated with lactic acid production even in the presence of oxygen, a phenomenon referred to as the "Warburg effect", to counteract cancer cell growth. We have tested 3 bromopyruvate (3-BrPA), an inhibitor of pyruvate-associated reactions. Firstly, we tested this agent, in vitro, in two mesothelioma cell lines. Cellular response would appear to depend on the mode of administration (immediately or 24 h after seeding). Depending on the line, 3-BrPA induced a cytostatic or cytotoxic effect. This effect was accompanied by cell death induction even in cells highly refractory to cisplatin. Mitochondrial apoptotic death appeared to involve both lines; however, a different death pathway such as necrosis cannot be excluded. Interestingly, 3-BrPA leads to a diminution of the expression of the anti apotptoic protein Mcl-1. We then tested 3-BrPA in vivo. Survival of nude mice bearing human mesothelioma was significantly prolonged (p < 0.0001). Toxicity and clinical studies should be performed to test 3- BrPA as local therapy for patients suffering from pleural or peritoneal mesothelioma. Association with cisplatin should be particularly considered. PMID- 22322893 TI - Yin Yang-1 inhibits tumor cell growth and inhibits p21WAF1/Cip1 complex formation with cdk4 and cyclin D1. AB - The GLI-Kruppel zinc finger factor yin yang-1 (YY1) is a complex protein that regulates a variety of processes including transcription, proliferation, development and differentiation. YY1 inhibits cell growth in a cell type-specific manner. The role played by YY1 in its control of tumor cell growth is unclear and controversial. We show here that YY1 can suppress the growth of different tumor cell types in vitro, including human breast carcinoma cells and glioblastoma cells. YY1 also blocked the growth of 13762 MAT mammary adenocarcinoma isografts in rats. YY1 inhibited 13762 MAT tumor growth by approximately 80% compared with the GFP alone group 21 days after injection. YY1 inhibited proliferating cell nuclear antigen (PCNA) expression and pRbSer249/Thr252 phosphorylation without influencing tumor microvascular density. Moreover, YY1 inhibited p21WAF1/Cip1 complex formation with cdk4 and cyclin D1. These findings demonstrate that YY1 can negatively regulate the growth of multiple malignant cell types. PMID- 22322894 TI - Evaluation of various insulin sensitivity indices in lean idiopathic hirsutism patients. AB - Hirsutism is characterized by excessive growth of terminal hair in a male pattern. Idiopathic hirsutism (IH) is a common cause of hirsutism. Since there are few data demonstrating IH is associated with insulin resistance, we tried to assess various insulin sensitivity indices in lean IH and compare with healthy subjects. A cross-sectional study was performed in 71 lean (BMI between 20-25 kg/m(2)) women (17-39 years old), 31 with IH and 40 healthy individuals. Blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), hepatic insulin sensitivity (ISI (HOMA)), Quicky index, reciprocal fasting insulin resistance index, fasting Belfiore index, and fasting glucose/insulin ration (GIR) were estimated using a single fasting sample of glucose and insulin levels. Raynaud indices calculated using the mathematical estimation in a single fasting sample of insulin levels were determined and compared in two groups. Fasting insulin, Raynaud index, HOMA-IR and Fasting insulin resistance index (FIRI) results were higher in IH group than in controls (p<0.01, for all). Fasting Belfiore index, QUICKI index, ISI(HOMA) and FIRI(-1) results were lower in IH group than in controls (p<0.01, for all). Our study showed that lean IH patients were more insulin resistant than healthy subjects. We propose that insulin sensitivity indices are useful methods for measuring insulin resistance in IH. PMID- 22322895 TI - The role of colour Doppler ultrasonography in the preoperative localization of parathyroid adenomas. AB - The aim of the present study was to evaluate the diagnostic accuracy and imaging patterns of colour Doppler ultrasonography (US) and compare it with grayscale US, 99m-Tc methoxyisobutylisonitrile (MIBI) scans, and combined US and MIBI scans in the preoperative diagnosis of parathyroid adenomas in patients with primary hyperparathyroidism (pHPT). From June 2007 to June 2011, 36 consecutive patients (seven men and 29 women) with pHPT underwent grayscale US, colour Doppler ultrasonography (CDUS), and 99m-Tc MIBI scans prior to parathyroidectomy with traditional unilateral neck dissection. All 36 patients with pHPT underwent parathyroidectomy at our university hospital. According to histopathology results, the sensitivity, specificity, and accuracy of MIBI and US scan were 88%, 94%, and 91%, and 70%, 100%, and 85%, respectively. The overall sensitivity and specificity of combined US and MIBI was 97% and 100% respectively. The overall sensitivity, specificity, and accuracy of CDUS in the correct diagnosis of parathyroid adenoma were 97%, 100%, and 98.6%, respectively. The sensitivity and specificity of US in the detection of parathyroid adenoma and differentiating it from other cervical masses reached up to 97% and 100%, respectively, by combining CDUS with grayscale evaluations of parathyroid adenoma. PMID- 22322896 TI - The effects of Na on high pressure phases of CuIn(0.5)Ga(0.5)Se(2) from ab initio calculation. AB - The effects of Na atoms on high pressure structural phase transitions of CuIn(0.5)Ga(0.5)Se(2) (CIGS) were studied by an ab initio method using density functional theory. At ambient pressure, CIGS is known to have chalcopyrite (I42d) structure. The high pressure phase transitions of CIGS were proposed to be the same as the order in the CuInSe(2) phase transitions which are I42d -> Fm3m -> Cmcm structures. By using the mixture atoms method, the Na concentration in CIGS was studied at 0.1, 1.0 and 6.25%. The positive mixing enthalpy of Na at In/Ga sites (Na(InGa)) is higher than that of Na at Cu sites (Na(Cu)). It confirmed previous studies that Na preferably substitutes on the Cu sites more than the (In, Ga) sites. From the energy-volume curves, we found that the effect of the Na substitutes is to reduce the hardness of CIGS under high pressure. The most significant effects occur at 6.25% Na. We also found that the electronic density of states of CIGS near the valence band maximum is increased noticeably in the chalcopyrite phase. The band gap is close in the cubic and orthorhombic phases. Also, the Na(Cu)-Se bond length in the chalcopyrite phase is significantly reduced at 6.25% Na, compared with the pure Cu-Se bond length. Consequently, the energy band gap in this phase is wider than in pure CIGS, and the gap increased at the rate of 31 meV GPa(-1) under pressure. The Na has a small effect on the transition pressure. The path of transformation from the cubic to orthorhombic phase was derived. The Cu-Se plane in the cubic phase displaced relatively parallel to the (In, Ga)-Se plane by 18% in order to transform to the Cmcm phase. The enthalpy barrier is 0.020 eV/atom, which is equivalent to a thermal energy of 248 K. We predicted that Fm3m and Cmcm can coexist in some pressure range. PMID- 22322897 TI - In vitro and in vivo characterisation of PEG-lipid-based micellar complexes of salmon calcitonin for pulmonary delivery. AB - PURPOSE: To investigate DSPE-PEG(2000)-based micellar formulations of salmon calcitonin (sCT) for their ability to improve pulmonary delivery. METHODS: Micelles were characterised by DLS and (31)P-NMR spectroscopy. Stability against sCT degrading peptidases, trypsin, alpha-chymotrypsin and neutrophil elastase as well as their influence on transepithelial absorption was investigated in vitro. In vivo performance of sCT micelles was studied in an experimental model of intratracheal aerosolisation into rats. RESULTS: Micelles with a mean hydrodynamic diameter of 12 nm spontaneously assembled, when a total concentration of 0.02 mM of PEG-lipid and sCT (at 1:1 molar ratio) was exceeded. Nuclear magnetic resonance confirmed the presence of small micellar structures. The micellar formulation showed increased stability against enzymatic digestion. In vitro studies also showed that sCT micelles were able to enhance transepithelial absorption. Data obtained from in vivo experiments provided evidence of significantly (P < 0.05) higher mean plasma concentrations of sCT, after inhalation of micelles compared to sCT solution, at 60 and 90 min, a significantly higher AUC (inf) and a relative bioavailability of 160 +/- 55% when compared to plain sCT solution. CONCLUSIONS: The herein described PEG-lipid micelles are promising carriers for enhanced pulmonary delivery of sCT. PMID- 22322898 TI - Drug release patterns and cytotoxicity of PEG-poly(aspartate) block copolymer micelles in cancer cells. AB - PURPOSE: To test physicochemical and biological properties of PEG-poly(aspartate) [PEG-p(Asp)] block copolymer micelles entrapping doxorubicin hydrochloride (DOX) through ionic interaction. METHODS: PEG-p(Asp) was synthesized from 5 kDa PEG and 20 Asp units. Carboxyl groups of p(Asp) were present as benzyl ester [PEG p(Asp/Bz)], sodium salt [PEG-p(Asp/Na)] or free acid [PEG-p(Asp/H)]. Block copolymers and DOX were mixed at various ratios to prepare polymer micelles, which were subsequently characterized to determine particle size, drug loading and release patterns, and cytotoxicity against prostate (PC3 and DU145) and lung (A549) cancer cell lines. RESULTS: PEG-p(Asp/Bz), Na- and H-micelles entrapped 1.1, 56.8 and 40.6 wt.% of DOX, respectively. Na- and H-micelles (<100 nm) showed time-dependent DOX release at pH 7.4, which was accelerated at pH 5.0. Na micelles were most stable at pH 7.4, retaining 31.8% of initial DOX for 48 h. Cytotoxicity of Na-micelles was 23.2% (A549), 28.5% (PC3) and 45.9% (DU145) more effective than free DOX. CONCLUSION: Ionic interaction appeared to entrap DOX efficiently in polymer micelles from PEG-p(Asp) block copolymers. Polymer micelles possessing counter ions (Na) of DOX in the core were the most stable, releasing drugs for prolonged time in a pH-dependent manner, and suppressing cancer cells effectively. PMID- 22322899 TI - Inclusion complex of novel curcumin analogue CDF and beta-cyclodextrin (1:2) and its enhanced in vivo anticancer activity against pancreatic cancer. AB - PURPOSE: Several formulations have been proposed to improve the systemic delivery of novel cancer therapeutic compounds, including cyclodextrin derivatives. We aimed to synthesize and characterize of CDF-beta-cyclodextrin inclusion complex (1:2) (CDFCD). METHODS: The compound was characterized by Fourier transform infrared, differential scanning calorimetry, powder X-ray diffraction studies, H1 & C13 NMR studies and scanning electron microscopic analysis. Its activity was tested against multiple cancer cell lines, and in vivo bioavailability was checked. RESULTS: CDF-beta-cyclodextrin was found to lower IC(50) value by half when tested against multiple cancer cell lines. It preferentially accumulated in the pancreas, where levels of CDF-beta-cyclodextrin in mice were 10 times higher than in serum, following intravenous administration of an aqueous CDF-beta cyclodextrin preparation. CONCLUSIONS: Novel curcumin analog CDF preferentially accumulates in the pancreas, leading to its potent anticancer activity against pancreatic cancer cells. Synthesis of such CDF-beta-cyclodextrin self-assembly is an effective strategy to enhance its bioavailability and tissue distribution, warranting further evaluation for CDF delivery in clinical settings for treatment of human malignancies. PMID- 22322900 TI - Borrelia and subsequent risk of solid tumors and hematologic malignancies in Sweden. PMID- 22322901 TI - Sun exposure may increase risk of prostate cancer in the high UV environment of New South Wales, Australia: a case-control study. PMID- 22322902 TI - The donor-acceptor biphenyl platform: a versatile chromophore for the engineering of highly efficient two-photon sensitive photoremovable protecting groups. AB - Different photoremovable protecting groups in the o-nitrobenzyl, phenacyl, and 2 (o-nitrophenyl)propyl series with a donor-acceptor biphenyl backbone, known to display excellent two-photon absorption cross-sections, were investigated in order to develop efficient two-photon sensitive photoremovable protecting groups. The 2-(o-nitrophenyl)propyl series was a more versatile platform to increase the two-photon sensitivity of photoremovable protecting groups, leading to the p alkoxy and p-bisalkylamino-4-nitro-[1,1'-biphenyl]-3-yl)propyl derivatives: PENB and EANBP respectively. Those two photoremovable protecting groups are to date the best caging groups for two-photon excitation at 800 and 740 nm respectively, offering attracting perspectives in chemical biology. PMID- 22322904 TI - Supraspinatus tendon tears at 3.0 T shoulder MR arthrography: diagnosis with 3D isotropic turbo spin-echo SPACE sequence versus 2D conventional sequences. AB - OBJECTIVE: To assess the diagnostic performance of shoulder MR arthrography with 3D isotropic fat-suppressed (FS) turbo spin-echo sequence (TSE-SPACE) for supraspinatus tendon tears in comparison with 2D conventional sequences at 3.0 T. MATERIALS AND METHODS: The study was HIPAA-compliant and approved by the institutional review board with a waiver of informed consent. Eighty-seven arthroscopically confirmed patients who underwent 3.0 T shoulder MR arthrography with 2D sequences and 3D TSE-SPACE were included in a consecutive fashion from March 2009 to February 2010. Two reviewers independently analyzed 2D sequences and 3D TSE-SPACE. Sensitivity, specificity, accuracy, and interobserver agreement (kappa) were compared between 2D sequences and 3D TSE-SPACE for full-thickness and partial-thickness supraspinatus tendon tears together and for partial thickness supraspinatus tendon tears alone. RESULTS: There were 33 full-thickness tears and 28 partial-thickness tears of supraspinatus tendons. For full-thickness and partial-thickness supraspinatus tendon tears together, the mean sensitivity, specificity, and accuracy of both readers were 96, 92, and 94% on 2D sequences and 91, 84, and 89% on 3D TSE-SPACE. For partial-thickness supraspinatus tendon tears alone, the mean sensitivity, specificity, and accuracy were 95, 92, and 94% on 2D sequences and 84, 85, and 84% on 3D TSE-SPACE. There was no statistical difference between 2D sequences and 3D TSE-SPACE. Interobserver agreements were almost perfect on 2D conventional sequences and substantial on 3D TSE-SPACE. CONCLUSION: Compared with 2D conventional sequences, MR arthrography using 3D TSE SPACE was comparable for diagnosing supraspinatus tendon tears despite limitations in detecting small partial-thickness tears and in discriminating between full-thickness and deep partial-thickness tears. PMID- 22322903 TI - Genetic variations in the ADAMTS12 gene are associated with schizophrenia in Puerto Rican patients of Spanish descent. AB - ADAMTS12 belongs to the family of metalloproteinases that mediate a communication between specific cell types and play a key role in the regulation of normal tissue development, remodeling, and degradation. Members of this family have been implicated in neurodegenerative and neuroinflammatory, as well as in muscular skeletal, cardiovascular, respiratory and renal diseases, and cancer. Several metalloproteinases have been associated with schizophrenia. In our previous study of the pedigree from a genetic isolate of Spanish origin in Puerto Rico, we identified a schizophrenia susceptibility locus on chromosome 5p13 containing ADAMTS12. This gene, therefore, is not only a functional but also a positional candidate gene for susceptibility to the disorder. In order to examine possible involvement of ADAMTS12 in schizophrenia, we performed mutation analysis of the coding, 5'- and 3'-untranslated, and putative promoter regions of the gene in affected members of the pedigree and identified 18 sequence variants segregated with schizophrenia. We then tested these variants in 135 unrelated Puerto Rican schizophrenia patients of Spanish origin and 203 controls and identified the intronic variant rs256792 (P = 0.0035; OR = 1.59; 95% CI = 1.16-2.17) and the two SNP haplotype rs256603-rs256792 (P = 0.0023; OR = 1.62; 95% CI = 1.19-2.21) associated with the disorder. The association remained significant after correction for multiple testing. Our data support the hypothesis that genetic variations in ADAMTS12 influence the risk of schizophrenia. PMID- 22322905 TI - Analysis of base and codon usage by rubella virus. AB - Rubella virus (RUBV), a small, plus-strand RNA virus that is an important human pathogen, has the unique feature that the GC content of its genome (70%) is the highest (by 20%) among RNA viruses. To determine the effect of this GC content on genomic evolution, base and codon usage were analyzed across viruses from eight diverse genotypes of RUBV. Despite differences in frequency of codon use, the favored codons in the RUBV genome matched those in the human genome for 18 of the 20 amino acids, indicating adaptation to the host. Although usage patterns were conserved in corresponding genes in the diverse genotypes, within-genome comparison revealed that both base and codon usages varied regionally, particularly in the hypervariable region (HVR) of the P150 replicase gene. While directional mutation pressure was predominant in determining base and codon usage within most of the genome (with the strongest tendency being towards C's at third codon positions), natural selection was predominant in the HVR region. The GC content of this region was the highest in the genome (>80%), and it was not clear if selection at the nucleotide level accompanied selection at the amino acid level. Dinucleotide frequency analysis of the RUBV genome revealed that TpA usage was lower than expected, similar to mammalian genes; however, CpG usage was not suppressed, and TpG usage was not enhanced, as is the case in mammalian genes. PMID- 22322906 TI - Practical quantum mechanics-based fragment methods for predicting molecular crystal properties. AB - Significant advances in fragment-based electronic structure methods have created a real alternative to force-field and density functional techniques in condensed phase problems such as molecular crystals. This perspective article highlights some of the important challenges in modeling molecular crystals and discusses techniques for addressing them. First, we survey recent developments in fragment based methods for molecular crystals. Second, we use examples from our own recent research on a fragment-based QM/MM method, the hybrid many-body interaction (HMBI) model, to analyze the physical requirements for a practical and effective molecular crystal model chemistry. We demonstrate that it is possible to predict molecular crystal lattice energies to within a couple kJ mol(-1) and lattice parameters to within a few percent in small-molecule crystals. Fragment methods provide a systematically improvable approach to making predictions in the condensed phase, which is critical to making robust predictions regarding the subtle energy differences found in molecular crystals. PMID- 22322907 TI - Undetected cognitive impairment and decision-making capacity in patients receiving hospice care. AB - OBJECTIVE: : Cognitive dysfunction is common in patients with advanced, life threatening illness and can be attributed to a variety of factors (e.g., advanced age, opiate medication). Such dysfunction likely affects decisional capacity, which is a crucial consideration as the end-of-life approaches and patients face multiple choices regarding treatment, family, and estate planning. This study examined the prevalence of cognitive impairment and its impact on decision-making abilities among hospice patients with neither a chart diagnosis of a cognitive disorder nor clinically apparent cognitive impairment (e.g., delirium, unresponsiveness). DESIGN: : A total of 110 participants receiving hospice services completed a 1-hour neuropsychological battery, a measure of decisional capacity, and accompanying interviews. RESULTS: : In general, participants were mildly impaired on measures of verbal learning, verbal memory, and verbal fluency; 54% of the sample was classified as having significant, previously undetected cognitive impairment. These individuals performed significantly worse than the other participants on all neuropsychological and decisional capacity measures, with effect sizes ranging from medium to very large (0.43-2.70). A number of verbal abilities as well as global cognitive functioning significantly predicted decision-making capacity. CONCLUSION: : Despite an absence of documented or clinically obvious impairment, more than half of the sample had significant cognitive impairments. Assessment of cognition in hospice patients is warranted, including assessment of verbal abilities that may interfere with understanding or reasoning related to treatment decisions. Identification of patients at risk for impaired cognition and decision making may lead to effective interventions to improve decision making and honor the wishes of patients and families. PMID- 22322908 TI - Racial differences in self-rated health diminishing from 1972 to 2008. AB - In addition to higher morbidity and mortality, Black adults have reported lower self-rated health than White adults. The purpose of this study was to evaluate the diminishing difference in self-rated health between races from 1972 to 2008. Data from 37,936 participants over a 36-year span of the General Social Survey were used to evaluate the effects of race and time on self-rated health. Results confirmed that Black adults reported significantly worse health than White adults. Overall health was rated slightly better across both groups as time went on ([Formula: see text] = .002, P < .0005). However, this increase in health ratings has slowed, even reversing with a decline in health ratings as of late ([Formula: see text] = -.014, P = .001). Significant interactions between race and time indicated that the racial difference on this self-rated health measure has changed over time. The rate of change in the difference has slowed over time ([Formula: see text] = -.010, P = .021), suggesting that the reduction in the racial difference in self-rated health may be decelerating. PMID- 22322909 TI - Internalized weight bias: ratings of the self, normal weight, and obese individuals and psychological maladjustment. AB - Current measures of internalized weight bias assess factors such as responsibility for weight status, mistreatment because of weight, etc. A potential complementary approach for assessing internalized weight bias is to examine the correspondence between individuals' ratings of obese people, normal weight people, and themselves on personality traits. This investigation examined the relationships among different measures of internalized weight bias, as well as the association between those measures and psychosocial maladjustment. Prior to the beginning of a weight loss intervention, 62 overweight/obese adults completed measures of explicit and internalized weight bias as well as body image, binge eating, and depression. Discrepancies between participants' ratings of obese people in general and ratings of themselves on both positive and negative traits predicted unique variance in measures of maladjustment above a traditional assessment of internalized weight bias. This novel approach to measuring internalized weight bias provides information above and beyond traditional measures of internalized weight bias and begins to provide insights into social comparison processes involved in weight bias. PMID- 22322910 TI - Self-efficacy and barriers to multiple behavior change in low-income African Americans with hypertension. AB - Behavioral risk factors are among the preventable causes of health disparities, yet long-term change remains elusive. Many interventions are designed to increase self-efficacy, but little is known about the effect on long-term behavior change in older, low-income African Americans, especially when facing more problematic barriers. A cohort of 185 low-income African-Americans with hypertension reported barriers they encountered while undergoing a multiple behavior change trial from 2002 to 2006. The purpose of the present study was to explore the relationships between self-efficacy, barriers, and multiple behavior change over time. Higher self-efficacy seemed to be partially helpful for smoking reduction and increasing physical activity, but not for following a low-sodium diet. Addiction was indirectly associated with less reduction in smoking through lower self-efficacy. Otherwise, different barriers were associated with behavior change than were associated with self-efficacy: being "too busy" directly interfered with physical activity and "traditions" with low-sodium diet; however, they were neither the most frequently reported barriers, nor associated with lower self-efficacy. This suggests that an emphasis on self-efficacy alone may be insufficient for overcoming the most salient barriers encountered by older African Americans. Additionally, the most common perceived barriers may not necessarily be relevant to long-term behavioral outcomes. PMID- 22322911 TI - Down-regulation of miR-125a-3p in human gastric cancer and its clinicopathological significance. AB - Recent reports have demonstrated that another strand of mature microRNA (miRNA), called microRNA* or 3p (5p) strand, which is generated from the same precursor miRNA (Pre-miR), has a crucial role in cellular function. We previously reported the tumor suppressive effect of miR-125a-5p in gastric cancer. The current study was designed to examine the function and clinical significance of miR-125a-3p, a partner strand of miR-125a-5p, in human gastric cancer. Quantitative RT-PCR was used to evaluate miR-125a-3p expression in 70 gastric cancer cases to determine the clinicopathologic significance of miR-125a-3p expression. In addition, the effect of miR-125a-3p on the proliferation of gastric cancer cells was investigated. Low expression levels of miR-125a-3p were associated with indicators of enhanced malignant potential such as tumor size (p=0.0002), tumor invasion (p=0.0149), lymph node metastasis (p=0.018), liver metastasis (p=0.016), peritoneal dissemination (p=0.03), advanced clinical stage (p=0.0037) and poor prognosis (p=0.0083). Multivariate analysis indicated that low miR-125a-3p expression was an independent prognostic factor for survival, while in vitro assays demonstrated that miR-125a-3p suppressed the proliferation of gastric cancer cells. MiR-125a-3p is a potent prognostic marker in gastric cancer. The clinical significance and tumor suppressive effect of miR-125a-3p, as well as previously reported miR-125a-5p, suggest that the functional role of another strand of the mature form miRNA cannot be ignored, at least in miR-125a biogenesis. PMID- 22322917 TI - Hyperglycaemia normalises insulin action on glucose metabolism but not the impaired activation of AKT and glycogen synthase in the skeletal muscle of patients with type 2 diabetes. AB - AIMS/HYPOTHESIS: In type 2 diabetes, reduced insulin-stimulated glucose disposal, primarily glycogen synthesis, is associated with defective insulin activation of glycogen synthase (GS) in skeletal muscle. Hyperglycaemia may compensate for these defects, but to what extent it involves improved insulin signalling to glycogen synthesis remains to be clarified. METHODS: Whole-body glucose metabolism was studied in 12 patients with type 2 diabetes, and 10 lean and 10 obese non-diabetic controls by means of indirect calorimetry and tracers during a euglycaemic-hyperinsulinaemic clamp. The diabetic patients underwent a second isoglycaemic-hyperinsulinaemic clamp maintaining fasting hyperglycaemia. Muscle biopsies from m. vastus lateralis were obtained before and after the clamp for examination of GS and relevant insulin signalling components. RESULTS: During euglycaemia, insulin-stimulated glucose disposal, glucose oxidation and non oxidative glucose metabolism were reduced in the diabetic group compared with both control groups (p < 0.05). This was associated with impaired insulin stimulated GS and AKT2 activity, deficient dephosphorylation at GS sites 2 + 2a, and reduced Thr308 and Ser473 phosphorylation of AKT. When studied under hyperglycaemia, all variables of insulin-stimulated glucose metabolism were normalised compared with the weight-matched controls. However, insulin activation and dephosphorylation (site 2 + 2a) of GS as well as activation of AKT2 and phosphorylation at Thr308 and Ser473 remained impaired (p < 0.05). CONCLUSIONS/INTERPRETATIONS: These data confirm that hyperglycaemia compensates for decreased whole-body glucose disposal in type 2 diabetes. In contrast to previous less well-controlled studies, we provide evidence that the compensatory effect of hyperglycaemia in patients with type 2 diabetes does not involve normalisation of insulin action on GS or upstream signalling in skeletal muscle. PMID- 22322918 TI - Hyperfiltration in type 1 diabetes: does it exist and does it matter for nephropathy? AB - AIMS/HYPOTHESIS: Hyperfiltration is widely regarded as a contributing factor to the development of microalbuminuria and progressive nephropathy in type 1 diabetes. However, recent studies have questioned this conclusion. METHODS: To address this conflicting evidence, we examined the association between hyperfiltration and progression to microalbuminuria in 2,318 adults with type 1 diabetes. We also compared the estimated GFR in our diabetic patients with rates observed in 6,247 adults from the Finnish general population, using age- and sex specific z scores. RESULTS: The distribution of estimated GFR in adults with type 1 diabetes and normoalbuminuria was not significantly different from that expected in the general population (p = 0.51, Mann-Whitney test). Type 1 diabetic patients with a higher estimated GFR were also no more likely to develop microalbuminuria over a median of 5.2 years of follow-up than those with normal estimated GFR. This was the case regardless of whether hyperfiltration was defined by an absolute threshold, deciles of estimated GFR or a z score, using creatinine- or cystatin-based clearance formulas in men or in women. CONCLUSIONS/INTERPRETATION: Together with other studies, these data suggest that creatinine- or cystatin-based estimates of GFR do not predict the development of microalbuminuria in patients with type 1 diabetes. Moreover, in the absence of incipient or overt nephropathy, conventionally determined renal function in patients with type 1 diabetes appears no different from that in the general population. This is hardly surprising, given that these individuals, by all definitions, do not have kidney disease. PMID- 22322919 TI - Relationship between diabetes risk and admixture in postmenopausal African American and Hispanic-American women. AB - AIMS/HYPOTHESIS: Type 2 diabetes is more prevalent in African-Americans (AFAs) and Hispanic-Americans (HAs) than in European-Americans. We assessed whether continental admixture was correlated with diabetes risk in these high-risk groups. METHODS: We estimated the proportion of sub-Saharan African (AFR), Amerindian (AMI) and European admixture using 92 ancestry-informative marker genotypes in 16,476 AFA and HA women from the Women's Health Initiative. Cox regression models were used to examine the association between admixture and diabetes risk, with and without accounting for socioeconomic status (SES) and adiposity measurements. RESULTS: AFR admixture was significantly associated with diabetes risk in AFA women when adjusting for entry age, neighbourhood SES and BMI or waist/hip ratio (WHR) (all p < 0.0001). In HA women, AMI admixture had significant associations with diabetes risk that remained significant after adjustment for SES and BMI (all p < 0.0005). In both AFAs and HAs, SES showed significant negative associations while BMI or WHR had significant positive associations with diabetes risk, with and without adjustment for genetic admixture. CONCLUSIONS/INTERPRETATION: In AFAs, admixture, SES and BMI/WHR each independently contribute to diabetes risk after accounting for each of the other factors; in HAs, admixture, SES and BMI each independently contribute to diabetes risk after accounting for each of the other factors, whereas admixture is not significantly associated with diabetes risk after accounting for SES and WHR. The findings emphasise the importance of considering both genetic and environmental causes in the aetiology of type 2 diabetes. PMID- 22322920 TI - Potassium intake and risk of incident type 2 diabetes mellitus: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. AB - AIMS/HYPOTHESIS: Serum potassium has been found to be a significant predictor of diabetes risk, but the effect of dietary potassium on diabetes risk is not clear. We sought to determine if dietary potassium is associated with risk of incident type 2 diabetes in young adults. METHODS: We used data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Potassium intake was measured by (1) an average of three 24 h urinary potassium collections at the 5-year study visit, and (2) the CARDIA dietary assessment instrument at baseline. Incident type 2 diabetes cases were ascertained on the basis of use of diabetes medication and laboratory measurements. Analyses were adjusted for relevant confounders including intake of fruit and vegetables and other dietary factors. RESULTS: Of 1,066 participants with urinary potassium measurements, 99 (9.3%) developed diabetes over 15 years of follow-up. In multivariate models, adults in the lowest urinary potassium quintile were more than twice as likely to develop diabetes as their counterparts in the highest quintile (HR 2.45; 95% CI 1.08, 5.59). Of 4,754 participants with dietary history measurements, 373 (7.8%) developed diabetes over 20 years of follow-up. In multivariate models, African-Americans had a significantly increased risk of diabetes with lower potassium intake, which was not found in whites. CONCLUSIONS/INTERPRETATION: Low dietary potassium is associated with increased risk of incident diabetes in African-Americans. Randomised clinical trials are needed to determine if potassium supplementation, from either dietary or pharmacological sources, could reduce the risk of diabetes, particularly in higher-risk populations. PMID- 22322921 TI - Delaying progression to type 2 diabetes among high-risk Spanish individuals is feasible in real-life primary healthcare settings using intensive lifestyle intervention. AB - AIMS/HYPOTHESIS: To assess the feasibility and effectiveness of an active real life primary care lifestyle intervention in preventing type 2 diabetes within a high-risk Mediterranean population. METHODS: A prospective cohort study was performed in the setting of Spanish primary care. White-European individuals without diabetes aged 45-75 years (n = 2,054) were screened using the Finnish Diabetes Risk Score (FINDRISC) and a subsequent 2 h OGTT. Where feasible, high risk individuals who were identified were allocated sequentially to standard care, a group-based or an individual level intervention (intensive reinforced DE PLAN [Diabetes in Europe-Prevention using Lifestyle, Physical Activity and Nutritional] intervention). The primary outcome was the development of diabetes according to WHO criteria. Analyses after 4-year follow-up were performed based on the intention-to-treat principle with comparison of standard care and the combined intervention groups. RESULTS: The standard care (n = 219) and intensive intervention (n = 333) groups were comparable in age (62.0/62.2 years), sex (64.4/68.2% women), BMI (31.3/31.2 kg/m(2)), FINDRISC score (16.2/15.8 points), fasting (5.3/5.2 mmol/l), 2 h plasma glucose (7.1/6.9 mmol/l) and self-reported interest to make lifestyle changes at baseline. Diabetes was diagnosed in 124 individuals: 63 (28.8%) in the standard care group and 61 (18.3%) in the intensive intervention group. During a 4.2-year median follow-up, the incidences of diabetes were 7.2 and 4.6 cases per 100 person-years, respectively (36.5% relative risk reduction, p < 0.005). The number of participants needed to be treated by intensive intervention for 4 years to reduce one case of diabetes was 9.5. CONCLUSIONS/INTERPRETATION: Intensive lifestyle intervention is feasible in a primary care setting and substantially reduces diabetes incidence among high risk individuals. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov NCT01519505. FUNDING: Commission of the European Communities, Institute of Health Carlos III, Spanish Ministry of Health and Department of Health, Generalitat de Catalunya. PMID- 22322922 TI - Gene expression profiling in MOLT-4 cells during gamma-radiation-induced apoptosis. AB - This study aims to identify the temporal changes in gene expression in MOLT-4, a leukemia cell line, in response to radiation and to present a comprehensive description of the pathways and processes that most significantly relate to the cellular biological responses. A global gene expression profile of 24,500 genes was performed on MOLT-4 tumor cells following exposure to 5 Gy of ionizing radiation ((60)Co) using a bead chip array (Illumina). Signaling pathways and processes significantly altered following irradiation were explored using MetaCore. Cellular viability [3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide], activation of cell cycle checkpoints [fluorescence activated cell sorting (FACS)], and induction of apoptosis (FACS, caspase assays) were evaluated to correlate these biological responses to the gene expression changes. Totally, 698 different genes displayed a significantly altered expression following radiation, and out of these transcripts, all but one showed increased expression. One hour following irradiation, the expression was changed only for a few genes. Striking changes appeared at later time-points. From 3 to 24 h post-irradiation, a significant fraction of the genes with altered expression were found to be involved in cell cycle checkpoints and their regulation (CDKN1A), DNA repair (GADD45A, DDB2, XPC), apoptosis induction (DR5, FasR, Apo-2L, Bax), and T-cell activation/proliferation (CD70, OX40L). Irradiated MOLT-4 cells were arrested at the G2-checkpoint, followed by a decrease in cell viability, most pronounced 48 h after exposure. The cell death was executed by induced apoptosis and was visualized by an increase in subG1 cells and an increased activation of initiator (caspase-8 and caspase-9) and execution (caspase-3) caspases. Activation of cell cycle arrest and apoptosis correlated well in time with the changes in gene expression of those genes important for these biological processes. Activation of the apoptotic signaling pathways in MOLT-4 cells following irradiation includes components from the intrinsic as well as the extrinsic apoptotic pathways. This study indicates that the altered gene expression pattern induced by irradiation is important for the sequential steps observed in MOLT-4 cells during apoptosis induction. PMID- 22322923 TI - Defatted sesame seed extract reduces brain oedema by regulating aquaporin 4 expression in acute phase of transient focal cerebral ischaemia in rat. AB - Brain oedema is the volumetric increase of brain tissue and is known to be linked to vascular factors, including the blood-brain barrier (BBB) and vascular permeability. Besides neuroprotection, inhibition of brain oedema also can be a method to protect the brain against ischaemic insult. Sesame is reported to have various beneficial effects on the cardiovascular and cerebrovascular systems. The neuroprotective effects of defatted sesame seed extract (DSE) in a transient middle cerebral artery occlusion (tMCAo) rat model were reported previously. The current study was planned to investigate whether the neuroprotective effects of DSE is related to brain oedema. The tMCAo rat model was used to investigate the brain water content (BWC) and Evans blue (EB) leakage. Aquaporin 4 (AQP4), matrix metalloproteinase (MMP)-2 and MMP-9 expressions at 4 and 24 h after ischaemia were analysed. In vitro zymography was performed to investigate the effects on MMPs activities. DSE (30, 100, and 300 mg/kg, p.o.) reduced BWC but not EB leakage. DSE inhibited AQP4 expression at 4 h but not at 24 h after ischaemia. It did not show any effects on MMPs expressions and activities. Therefore, DSE might be effective on brain oedema by AQP4 regulation during the acute phase of ischaemia. PMID- 22322924 TI - Serum taurine and risk of coronary heart disease: a prospective, nested case control study. AB - PURPOSE: Taurine (2-aminoethanesulfonic acid), a molecule obtained from diet, is involved in bile acid conjugation, blood pressure regulation, anti-oxidation and anti-inflammation. We performed the first prospective study of taurine and CHD risk. METHODS: We conducted a case-control study nested in the New York University Women's Health Study to evaluate the association between circulating taurine levels and risk of coronary heart disease (CHD). Taurine was measured in two yearly pre-diagnostic serum samples of 223 CHD cases and 223 matched controls and averaged for a more reliable measurement of long-term taurine levels. RESULTS: Mean serum taurine was positively related to age and dietary intake of poultry, niacin, vitamin B1, fiber and iron, and negatively related to dietary intake of saturated fat (all p values <= 0.05). There was no statistically significant association between serum taurine levels and the risk of CHD in the overall study population. The adjusted ORs for CHD in increasing taurine tertiles were 1.0 (reference), 0.85 (95% CI, 0.51-1.40) and 0.66 (0.39-1.13; p for trend = 0.14). There was a significant inverse association between serum taurine and CHD risk among women with high total serum cholesterol (>250 mg/dL) (adjusted OR = 0.39 (0.19-0.83) for the third versus first tertile; p for trend = 0.02) but not among those with low total serum cholesterol (p for interaction = 0.01). The data suggest a possible inverse association of serum taurine with diabetes and hypertension risk. CONCLUSIONS: The findings suggest that high levels of taurine may be protective against CHD among individuals with high serum cholesterol levels. PMID- 22322925 TI - A composite score combining waist circumference and body mass index more accurately predicts body fat percentage in 6- to 13-year-old children. AB - PURPOSE: Body mass index (BMI) and waist circumference (WC) are widely used to predict % body fat (BF) and classify degrees of pediatric adiposity. However, both measures have limitations. The aim of this study was to evaluate whether a combination of WC and BMI would more accurately predict %BF than either alone. METHODS: In a nationally representative sample of 2,303 6- to 13-year-old Swiss children, weight, height, and WC were measured, and %BF was determined from multiple skinfold thicknesses. Regression and receiver operating characteristic (ROC) curves were used to evaluate the combination of WC and BMI in predicting %BF against WC or BMI alone. An optimized composite score (CS) was generated. RESULTS: A quadratic polynomial combination of WC and BMI led to a better prediction of %BF (r (2) = 0.68) compared with the two measures alone (r (2) = 0.58-0.62). The areas under the ROC curve for the CS [0.6 * WC-SDS + 0.4 * BMI SDS] ranged from 0.962 +/- 0.0053 (overweight girls) to 0.982 +/- 0.0046 (obese boys) and were somewhat greater than the AUCs for either BMI or WC alone. At a given specificity, the sensitivity of the prediction of overweight and obesity based on the CS was higher than that based on either WC or BMI alone, although the improvement was small. CONCLUSION: Both BMI and WC are good predictors of %BF in primary school children. However, a composite score incorporating both measures increased sensitivity at a constant specificity as compared to the individual measures. It may therefore be a useful tool for clinical and epidemiological studies of pediatric adiposity. PMID- 22322926 TI - Endothelium/nitric oxide mechanism mediates vasorelaxation and counteracts vasoconstriction induced by low concentration of flavanols. AB - PURPOSE: At relatively low concentrations, flavanols induce inconsistent effects on isolated arterial tone, sometimes explained as being due to a structure activity relationship. The aim of our study was to investigate the effects of two flavanols at different doses on arterial functional state. METHODS: The effects of two catechins, (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin (EP), on rat-isolated aorta tone were investigated on resting tension and on precontracted preparations, both in the presence and in the absence of endothelium. RESULTS: At resting tension, endothelium-intact preparations, EGCG and EP (0.01-10 MUM), induced a slight concentration-dependent, non-significant contraction. On endothelium-denuded preparations, both EGCG and EP induced a concentration-dependent contraction (significance at 0.1 and 1 MUM concentrations of the two compounds, respectively). In phenylephrine (PE) (1 MUM) precontracted, endothelium-intact preparations, EGCG and EP (0.01-10 MUM), induced a concentration-dependent vasorelaxation, reaching significance at 1 MUM concentration of both agonists. On endothelium-denuded preparations, EGCG and EP did not significantly affect PE (0.3 MUM)-induced tone. In endothelium-intact precontracted preparations, Nomega nitro-L-arginine (L-NNA), a nitric oxide synthase (NOS) activity inhibitor, abolished the vasorelaxant effect of EGCG and EP (0.01-10 MUM). At high concentrations, EGCG and EP (100 MUM) elicited a marked relaxation. This was significantly larger in the presence than in the absence of endothelium or in the presence of L-NNA. CONCLUSIONS: Our findings highlight the important role played by an endothelium/NO-mechanism in the regulation of basal tone and in both mediating vasorelaxation and counteracting vasoconstriction induced by low concentrations of flavanols in rat thoracic aorta. PMID- 22322927 TI - [Overview: transportsome as a fundamental unit for the onset of diseases]. PMID- 22322928 TI - [Transportsome in biliary cholesterol secretion]. PMID- 22322929 TI - [Functional interaction between Na(+)/Ca(2+) exchanger and sodium-transporting proteins in plasma membrane microdomains]. PMID- 22322930 TI - [Aquaporin complex regulating urine concentration]. PMID- 22322931 TI - [Insulin resistance-induced hypertension and perivascular nerves-an approach to elucidate the mechanisms involved]. PMID- 22322932 TI - [Pharmacological and clinical profiles of Fulvestrant (Faslodex((r))) in the treatment of advanced or recurrenced breast cancer]. PMID- 22322933 TI - Comparative evaluation of synthetic anti-HER2 Affibody molecules site specifically labelled with 111In using N-terminal DOTA, NOTA and NODAGA chelators in mice bearing prostate cancer xenografts. AB - PURPOSE: In disseminated prostate cancer, expression of human epidermal growth factor receptor type 2 (HER2) is one of the pathways to androgen independence. Radionuclide molecular imaging of HER2 expression in disseminated prostate cancer might identify patients for HER2-targeted therapy. Affibody molecules are small (7 kDa) targeting proteins with high potential as tracers for radionuclide imaging. The goal of this study was to develop an optimal Affibody-based tracer for visualization of HER2 expression in prostate cancer. METHODS: A synthetic variant of the anti-HER2 Z(HER2:342) Affibody molecule, Z(HER2:S1), was N terminally conjugated with the chelators DOTA, NOTA and NODAGA. The conjugated proteins were biophysically characterized by electrospray ionization mass spectroscopy (ESI-MS), circular dichroism (CD) spectroscopy and surface plasmon resonance (SPR)-based biosensor analysis. After labelling with (111)In, the biodistribution was assessed in normal mice and the two most promising conjugates were further evaluated for tumour targeting in mice bearing DU-145 prostate cancer xenografts. RESULTS: The HER2-binding equilibrium dissociation constants were 130, 140 and 90 pM for DOTA-Z(HER2:S1), NOTA-Z(HER2:S1) and NODAGA Z(HER2:S1), respectively. A comparative study of (111)In-labelled DOTA Z(HER2:S1), NOTA-Z(HER2:S1) and NODAGA-Z(HER2:S1) in normal mice demonstrated a substantial influence of the chelators on the biodistribution properties of the conjugates. (111)In-NODAGA-Z(HER2:S1) had the most rapid clearance from blood and healthy tissues. (111)In-NOTA-Z(HER2:S1) showed high hepatic uptake and was excluded from further evaluation. (111)In-DOTA-Z(HER2:S1) and (111)In-NODAGA Z(HER2:S1) demonstrated specific uptake in DU-145 prostate cancer xenografts in nude mice. The tumour uptake of (111)In-NODAGA-Z(HER2:S1), 5.6 +/- 0.4%ID/g, was significantly lower than the uptake of (111)In-DOTA-Z(HER2:S1), 7.4 +/- 0.5%ID/g, presumably because of lower bioavailability due to more rapid clearance. (111)In NODAGA-Z(HER2:S1) provided higher tumour-to-blood ratio, but somewhat lower tumour-to-liver, tumour-to-spleen and tumour-to-bone ratios. CONCLUSION: Since distant prostate cancer metastases are situated in bone or bone marrow, the higher tumour-to-bone ratio is the most important. This renders (111)In-DOTA Z(HER2:S1) a preferable agent for imaging of HER2 expression in disseminated prostate cancer. PMID- 22322935 TI - Electronic structure of ytterbium-implanted GaN at ambient and high pressure: experimental and crystal field studies. AB - The results of high-pressure low-temperature optical measurements in a diamond anvil cell of bulk gallium nitride crystals implanted with ytterbium are reported in combination with crystal field calculations of the Yb(3+) energy levels. Crystal field analysis of splitting of the (2)F(7/2) and (2)F(5/2) states has been performed, with the aim of assigning all features of the experimental luminescence spectra. A thorough analysis of the pressure behavior of the Yb(3+) luminescence lines in GaN allowed the determination of the ambient-pressure positions and pressure dependence of the Yb(3+) energy levels in the trigonal crystal field as well as the pressure-induced changes of the spin-orbit coupling coefficient. PMID- 22322936 TI - Diagnoses unveiled by early bronchoscopy in children with leukemia and pulmonary infiltrates. AB - Pulmonary complications in children with leukemia often display nonspecific clinical and radiologic manifestations that lead to a delay in diagnosis. The role of fiberoptic bronchoscopy (FOB) and the proper time for its performance are controversial. The aim of our study was to evaluate the frequency and nature of specific diagnoses revealed by FOB. Children with leukemia submitted to FOB because of suspicion of pulmonary involvement (mainly pneumonia) were retrospectively analyzed. A total of 33 FOB procedures performed in 31 patients (20 males) with an average age of 9.4 years (range, 3.5 to 15 y) were evaluated. Microorganisms isolated from 21 (63.6%) bronchoalveolar lavage samples were mainly fungi including Candida in 13 cases (39.4%) and Aspergillus in 3 cases (9.1%). Isolation rate in 10 procedures performed within the first 3 days was 90%. Tracheobronchitis was present in > 50% of patients, pulmonary hemorrhage was seen in 7 (21.0%) patients, and leukemic infiltration was demonstrated in 2 patients (6.1%), among other conditions visualized by FOB. Complications of FOB were minimal and transient. Our study suggests that FOB is a useful and safe procedure in patients with leukemia and pulmonary infiltrates. The earlier the FOB was performed, the higher the isolation rate of causative agents. In addition, this procedure allowed the identification of noninfectious airway comorbidities. Further studies in regard to this issue are warranted. PMID- 22322937 TI - X-linked hyper IgM syndrome: a novel sequence variant associated with an atypical mild phenotype. AB - X-linked hyper IgM syndrome is associated with abnormalities in the gene encoding CD40 ligand (CD40LG). A typical phenotype evolves during infancy in affected males. This phenotype includes neutropenia, dysgammaglobulinemia, bacterial sinopulmonary infections, and opportunistic infections. In the absence of the typical phenotypic features, clinicians must maintain a high level of suspicion for X-linked hyper IgM syndrome. We describe a unique hemizygous CD40LG mutation which was discovered in a 12-year-old boy with chronic severe neutropenia, a normal IgG level, and absence of sinopulmonary or opportunistic infections. The clinical implications of this mutation and associated atypical phenotype are discussed. PMID- 22322938 TI - Intrabone cord blood hematopoietic stem cell transplantation in a subset of very high-risk pediatric patients: a safety and feasibility pilot study. AB - The main limit of umbilical cord blood hematopoietic stem cell transplantation is a more difficult engraftment related to the number of cells infused per kilogram of recipient body weight. This limit makes the cord blood a suboptimal source of hematopoietic stem cells for transplantation in case of difficult engraftment situations. Direct intrabone cord blood (CB) injection has been recently investigated as a solution to cell dose problem in the adults population, but there is a lack of data concerning this approach in pediatric patients. Here, we describe 5 pediatric patients undergoing intrabone cord blood transplantation (IBCBT) for different diseases characterized by a high risk of posttransplant graft failure. The conditioning regimen differed according to the disease, whereas the GvHD prophylaxis consisted of cyclosporine, mycophenolate, and ATG. The median numbers of total nucleated cells infused and CD34(+) cells were 3.3 * 10(7)/kg, 2 * 10(5)/kg. All the patients showed complete hematological recovery and complete donor engraftment. No patient had secondary graft failure, whereas 1 patient relapsed 6 months after IBCBT. No patient died of transplant-related complications. Our results show that IBCBT is safe and feasible in pediatrics as well, and suggest that IBCBT might be an attractive option to overcome some limits of umbilical cord blood hematopoietic stem cell transplantation. PMID- 22322939 TI - Attitudes regarding analgesic use and pain expression in parents of children with cancer. AB - BACKGROUND: Children with cancer often experience significant levels of pain and their pain is generally undermanaged. Management of care to patients with cancer has shifted from the hospital to the home, and as such parents are charged with managing children's pain. However, parents may have misconceptions of analgesic use, which can lead to undertreatment of pain in children. The purpose of this study is to examine attitudes toward pain medication and perceptions of pain expression among parents of children undergoing cancer treatment. PROCEDURE: Parents of children who were undergoing cancer treatment at a hospital were recruited to take part in a survey study. A total of 187 parents completed a survey examining their attitudes toward medication and perceptions of pain expression in children. RESULTS: Many parents reported concerns regarding analgesic use to treat their children's pain and misconceptions about how children can express pain. Regression analyses noted that parental perceptions of pain expression were related to children's experience of chronic or recurring pain and the 2 dimensions of child temperament: emotionality and sociability. CONCLUSIONS: Many parents of children with cancer have misconceptions regarding issues of pain management; these misconceptions can potentially lead to undertreatment of pain in children. These misconceptions are associated with aspects of children's temperament. PMID- 22322940 TI - Serum ferritin is a cost-effective laboratory marker for hemophagocytic lymphohistiocytosis in the developing world. AB - Hemophagocytic lymphohistiocytosis (HLH) is a rare disease in children and presents many diagnostic difficulties. Without prompt intervention, the disease typically runs a rapidly fatal course. Diagnostic criteria were proposed by the Histiocyte Society in 1991 and have since been modified. Included in these criteria is a ferritin level >500 mcg/L. Although not diagnostic, a high ferritin level is highly suggestive of HLH. Serum ferritin assays are more accessible and cost-effective compared with other biochemical markers, particularly in resource limited settings. Fifteen patients with HLH were treated at Red Cross War Memorial Children's Hospital between 1991 and 2010. Hyperferritinemia was a consistently reliable finding (93%) compared with either serum fibrinogen or triglycerides, which were elevated in only half of the patients. It is our contention that analysis of a complete blood count and serum ferritin (in addition to clinical criteria and tissue examination of marrow and/or cerebrospinal fluid) is probably the single most cost-effective and clinically helpful means to make the diagnosis of HLH when laboratory access is limited. PMID- 22322941 TI - Sickle cell disease subphenotypes in patients from Southwestern Province of Saudi Arabia. AB - Sickle cell disease (SCD) is common in the Eastern and Southwestern (SW) Provinces of Saudi Arabia. We studied 159 patients with SCD to better characterize its phenotype in the SW Province, where patients usually have a HBB haplotype of African origin. All cases had history and examination, chart review, and laboratory testing. Blood tests were obtained during steady state and included: complete blood count, reticulocytes, hemoglobin electrophoresis, lactate dehydrogenase, and G6PD level. HBB haplotype and presence of alpha thalassemia were also determined. Frequency of various SCD complications was as follows: painful episodes of variable severity occurred in majority of patients (98%), osteonecrosis (14%), acute chest syndrome (22%), splenic sequestration (23%), gallstones (34%), stroke (7.5%), priapism (2.6%), serious infections (11.5%), and persistent splenomegaly (11%) beyond 5 years of age. No patient had leg ulcer. History of asthma and high steady state white blood cells count were associated with increased risk of acute chest syndrome. Coinheritance of alpha thalassemia was associated with a lower frequency of gallstones. Higher fetal hemoglobin level was associated with persistent splenomegaly but not with other complications. Splenic sequestration was more common among males and was associated with lower steady state hemoglobin. SCD phenotype in the SW Province is variable and comparable with African Americans except for the rarity of priapism and the absence of leg ulcers. Fetal hemoglobin level was not associated with SCD vaso-occlusive complications. New genetic modifiers and environmental factors might modulate the phenotype of SCD in Saudi Arabia. PMID- 22322942 TI - Mediastinal seminoma occurring in Down syndrome. AB - The increased incidence of testicular tumor occurrence, especially seminoma, in Down syndrome has been well documented. However, primary mediastinal seminoma occurring in Down syndrome has not been reported. Incidental discovery of an anterior mediastinal tumor was made in a 28-year-old Japanese man with Down syndrome, who had been scheduled for bone marrow transplantation to treat aplastic anemia. Histopathological findings of the resected tumor were typical of seminoma. This case indicates that seminoma can occur in the mediastinum in addition to testis in Down syndrome. PMID- 22322943 TI - Cell cycle control of Wnt/beta-catenin signalling by conductin/axin2 through CDC20. AB - Wnt/beta-catenin signalling regulates cell proliferation by modulating the cell cycle and is negatively regulated by conductin/axin2/axil. We show that conductin levels peak at G2/M followed by a rapid decline during return to G1. In line with this, Wnt/beta-catenin target genes are low at G2/M and high at G1/S, and beta catenin phosphorylation oscillates during the cell cycle in a conductin-dependent manner. Conductin is degraded by the anaphase-promoting complex/cyclosome cofactor CDC20. Knockdown of CDC20 blocks Wnt signalling through conductin. CDC20 resistant conductin inhibits Wnt signalling and attenuates colony formation of colorectal cancer cells. We propose that CDC20-mediated degradation of conductin regulates Wnt/beta-catenin signalling for maximal activity during G1/S. PMID- 22322944 TI - RWD domain: a recurring module in kinetochore architecture shown by a Ctf19-Mcm21 complex structure. AB - The proteins Ctf19, Okp1, Mcm21 and Ame1 are the components of COMA, a subassembly of budding-yeast kinetochores. We have determined the crystal structure of a conserved COMA subcomplex--the Ctf19-Mcm21 heterodimer--from Kluyveromyces lactis. Both proteins contain 'double-RWD' domains, which together form a Y-shaped framework with flexible N-terminal extensions. The kinetochore proteins Csm1, Spc24 and Spc25 have related single RWD domains, and Ctf19 and Mcm21 associate with pseudo-twofold symmetry analogous to that in the Csm1 homodimer and the Spc24-Spc25 heterodimer. The double-RWD domain core of the Ctf19-Mcm21 heterodimer is sufficient for association with Okp1-Ame1; the less conserved N-terminal regions may interact with components of a more extensive 'CTF19 complex'. Our structure shows the RWD domain to be a recurring module of kinetochore architecture that may be present in other kinetochore substructures. Like many eukaryotic molecular machines, kinetochores may have evolved from simpler assemblies by multiplication of a few ancestral modules. PMID- 22322945 TI - What doesn't kill you makes you dumber. Strengthening the link between infectious disease, intelligence and personality. PMID- 22322946 TI - Expression of the Gbeta5/R7-RGS protein complex in pituitary and pancreatic islet cells. PMID- 22322948 TI - Surgery in esophageal and gastric cancer patients: what is the role for nutrition support in your daily practice? AB - Cancers of the esophagus and stomach have a major impact on patients' nutritional status by virtue of these organs' inherent digestive functions. Many patients with these cancers will require surgical intervention, which imposes further metabolic demands and compounds preexisting nutritional disorders. Patients with esophagogastric cancer are likely to have lost weight by the time the diagnosis is made. This fact alone is of clinical importance, because it is well known that patients who have lost weight will have higher operative mortality and morbidity rates than patients who maintain their weight. Initial assessment of patients with esophagogastric cancer should include a routine evaluation of nutritional status. This will allow the identification of patients who are at risk of complications, particularly in the postoperative setting. These patients should be targeted for specific nutritional support. PMID- 22322947 TI - A new insight of mechanisms, diagnosis and treatment of diabetic cardiomyopathy. AB - Diabetes mellitus is one of the most common chronic diseases across the world. Cardiovascular complication is the major morbidity and mortality among the diabetic patients. Diabetic cardiomyopathy, a new entity independent of coronary artery disease or hypertension, has been increasingly recognized by clinicians and epidemiologists. Cardiac dysfunction is the major characteristic of diabetic cardiomyopathy. For a better understanding of diabetic cardiomyopathy and necessary treatment strategy, several pathological mechanisms such as impaired calcium handling and increased oxidative stress, have been proposed through clinical and experimental observations. In this review, we will discuss the development of cardiac dysfunction, the mechanisms underlying diabetic cardiomyopathy, diagnostic methods, and treatment options. PMID- 22322949 TI - Paget's disease as a local recurrence after nipple-sparing mastectomy: clinical presentation, treatment, outcome, and risk factor analysis. AB - BACKGROUND: Paget's disease is a rare clinical and histological type of local recurrence (LR) after breast cancer treatment both in case of conservative surgery or nipple-sparing mastectomy (NSM) with or without intraoperative radiation. METHODS: We performed an analysis of 861 NSM with electron beam intraoperative radiotherapy (ELIOT) patients treated at the European Institute of Oncology from 2002 to 2008, focused on Paget's disease local recurrence. RESULTS: In 861 patients (713 invasive carcinoma and 148 intraepithelial neoplasia), there were 36 local recurrences (4.18%), and among these were 7 Paget's disease local recurrences (0.8%). Median follow-up was 50 months. Four cases presented with nipple areola complex (NAC) erosions, two crusted lesions, and one ulcerated NAC. The average latency period from the NSM to Paget's disease local recurrence is 32 months (range, 12-49). Complete NAC removal was performed in all seven recurrences. The average follow-up after NAC removal was 47.4 months (range, 20 78). We found neither locoregional relapse nor metastatic event in this group. All patients were alive without disease. CONCLUSIONS: Paget's disease local recurrence can be found in a significant proportion after NSM. Any suspicious lesion on NAC requires prompt pathological confirmation. Primary carcinoma with ductal intraepithelial neoplasia or invasive ductal carcinoma with extensive in situ component, negative hormonal receptor, high pathological grade, overexpression of HER2/neu, and "HER2 positive (nonluminal)" subtype tend to be significantly associated with more Paget's disease local recurrence and should be followed carefully. PMID- 22322950 TI - Parietal peritonectomy. AB - Parietal peritonectomy is an initial part of cytoreductive surgery in patients with peritoneal surface malignancy. After this dissection, the necessary visceral resections, other peritonectomy procedures, and perioperative hyperthermic chemotherapy are administered. The parietal peritoneum is an immobile portion of the abdominal and pelvic surface area that is often involved by cancer implants in patients with carcinomatosis or peritoneal mesothelioma. The dependent peritoneal surfaces, such as the right retrohepatic space, paracolic sulcus, and pelvis, are involved as a result of gravitational forces. The undersurfaces of the diaphragm and omentums are involved because of major peritoneal fluid resorption at these anatomic sites. Before the parietal peritonectomy is initiated, a peritoneal window is created to digitally and visually inspect the undersurface of the anterior abdominal wall, small bowel, and small bowel mesentery. This inspection is frequently repeated so that parietal peritoneum is removed only where there is visible evidence of cancer implants. Electrosurgery is used as a dissection tool. The dissection proceeds in a centripetal fashion starting at the edges of the large midline abdominal incision and proceeding to the attachments of the peritoneum to the viscera. Initially, exposure is maintained with traction sutures from the skin edge to the fixed retractor. As the dissection deepens, a self-retaining retractor is positioned. Generally, the parietal peritonectomy takes approximately 21/2 h and does not require blood replacement. After the parietal peritonectomy, additional cytoreductive surgical procedures and then perioperative chemotherapy are performed. PMID- 22322951 TI - Sentinel lymph node procedure leads to upstaging of patients with resectable colon cancer: results of the Swiss prospective, multicenter study sentinel lymph node procedure in colon cancer. AB - BACKGROUND: The value of the sentinel lymph node (SLN) procedure in colon cancer patients remains a matter of debate. The objective of this prospective, multicenter trial was 3-fold: to determine the identification rate and accuracy of the SLN procedure in patients with resectable colon cancer; to evaluate the learning curve of the SLN procedure; and to assess the extent of upstaging due to the SLN procedure. METHODS: One hundred seventy-four consecutive colon cancer patients were enrolled onto this prospective trial. They underwent an intraoperative SLN procedure with isosulfan blue 1% injected peritumorally followed by open standard colon resection with oncologic lymphadenectomy. Three levels of each SLN were stained with hematoxylin and eosin (H&E) and immunostained with the pancytokeratin marker AE1/AE3 if H&E was negative. RESULTS: SLN identification rate and accuracy were 89.1% and 83.9%, respectively. SLN were significantly more likely to contain tumor infiltrates than non-SLN (P < 0.001). Both SLN identification rate (P = 0.021) and the sensitivity of the procedure (P = 0.043) significantly improved with experience. The use of immunohistochemistry in SLN resulted in an upstaging of 15.4% (16 of 104) stage I and II patients considered node-negative in initial H&E analysis. CONCLUSIONS: The SLN procedure for colon cancer has good identification and accuracy rates, which further improve with increasing experience. Most importantly, the SLN procedure results in upstaging of >15% of node-negative patients. The potential advantage of performing the SLN procedure appears to be particularly important in these patients because they may potentially benefit from adjuvant therapy. PMID- 22322952 TI - Medullary thyroid carcinoma: ethical issues for the surgeon. AB - Medullary thyroid cancer is a disease with an established genetic inheritance pattern for which evidence-based guidelines recommend genetic testing and subsequent management of affected patients and their family members. The perceived stigma of genetic testing, coupled with issues involving confidentiality and disclosure, create potential conflict and confusion. In some cases, there is a need for genetic testing and prophylactic surgery in children, augmenting the need for a judicious approach that balances respect for individual autonomy and parental rights with the best interest of the child. We provide an overview of the ethical issues facing surgeons caring for patients with familial medullary thyroid carcinoma, and recommend interventions and resources to assist in decision making in these difficult situations. PMID- 22322953 TI - Abstracts of the 65th Annual Cancer Symposium of the Society of Surgical Oncology. Orlando, Florida, USA. March 21-24, 2012. PMID- 22322954 TI - Prognostic significance of telomerase activity and human telomerase reverse transcriptase expression in ampullary carcinoma. AB - BACKGROUND: Telomerase activity and human telomerase reverse transcriptase (TERT) have been reported as markers of tumor aggressiveness and poor prognosis in several digestive cancers. In the present study, we examined telomerase activity and TERT expression in ampullary carcinoma to determine whether these parameters could be used as indicators of aggressiveness and prognosis. METHODS: Telomerase activity was analyzed by using the telomeric repeat amplification protocol assay, and TERT was examined by immunohistochemistry in ampullary carcinoma tissue samples resected from 46 patients. RESULTS: Telomerase activity was detected in 42 (91.3%) ampullary carcinomas and 27 (58.7%) showed high activity, whereas TERT expression was detected in 35 (76.1%), including 21 with weak expression and 14 with strong expression. Univariate analysis revealed that histological grade (P = 0.029), tumor depth (P < 0.001), nodal status (P = 0.013), UICC stage (P = 0.009), perineural invasion (P < 0.001), and telomerase activity (P = 0.031) were significantly associated with disease-specific survival. In multivariate analysis, only telomerase activity remained an independent predictor of prognosis (P = 0.043). There was no statistical significance for survival among the three grades of TERT expression (P = 0.054); however, in subgroup analysis, patients with strong TERT expression showed significantly poorer prognosis than those without TERT expression (P = 0.013). CONCLUSIONS: Our results suggest that high telomerase activity and strong TERT expression may serve as new prognostic markers for evaluating the prognosis of patients with resected ampullary carcinoma. PMID- 22322955 TI - MicroRNA-10b is a prognostic indicator in colorectal cancer and confers resistance to the chemotherapeutic agent 5-fluorouracil in colorectal cancer cells. AB - PURPOSE: Recent evidence has shown that altered patterns of microRNA (miRNA) expression correlate with various human cancers. We investigated the clinical significance of miR-10b and its involvement in chemotherapeutic resistance to 5 fluorouracil (5-FU), which is a key component of common chemotherapy regimens in colorectal cancer. METHODS: Quantitative RT-PCR was used to evaluate the clinicopathologic significance of miR-10b expression in 88 colorectal cancer cases. We also investigated the chemotherapeutic sensitivity to 5-FU in miR-10b overexpressing colorectal cancer cells. To explore the mechanism of chemoresistance in miR-10b transfected cells, we examined whether miR-10b inhibits the pro-apoptotic BH3-only Bcl-2 family member BIM(BCL2L11), a key mediator of chemotherapy-induced cell death. RESULTS: High level miR-10b expression was found to be significantly associated with high incidence of lymphatic invasion (P = 0.0257) and poor prognosis (P = 0.0057). Multivariate analysis indicated that high miR-10b expression is an independent prognostic factor for survival. In vitro studies revealed that miR-10b directly inhibits pro apoptotic BIM, and the overexpression of miR-10b confers chemoresistance in colorectal cancer cells to 5-FU. CONCLUSIONS: MiR-10b is a novel prognostic marker in colorectal cancer. Moreover, the expression of miR-10b is a potential indicator of chemosensitivity to the common 5-FU-based chemotherapy regimen. PMID- 22322956 TI - Treatment management of small renal masses in the 21st century: a paradigm shift. AB - BACKGROUND: Partial (PN) or radical nephrectomy (RN) represents the standard of care for patients with small renal masses. Active surveillance (AS) also may be considered. We examined the rates of PN, RN, and AS within a contemporary population-based cohort. METHODS: Using the surveillance, epidemiology and end results database, we identified 26,468 patients diagnosed with T1aN0M0 renal cell carcinoma, between years 1988 and 2008. Determinants of PN and AS were assessed using logistic regression analyses within surgically managed patients and within the entire cohort, respectively. RESULTS: Overall, 8,966 (34%), 14,705 (56%), and 2,797 (11%) patients underwent PN, RN, and AS, respectively. The rate of PN increased (4.7% in 1988 to 40.4% in 2008, P<0.001), whereas the rate of RN decreased over time (92.9% in 1988 to 41.4% in 2008, P<0.001). The rate of AS increased over time (2.4% in 1988 to 18.2% in 2008, P<0.001). In multivariable analyses, the determinants for PN consisted of more contemporary year of diagnosis, younger patient age, male gender, Caucasian race, married status, and decreasing tumor size (all P<=0.003). The determinants of AS consisted of more contemporary year of diagnosis, more advanced age, male gender, decreasing tumor size, and unmarried marital status (all P<=0.001). Regional differences for management of localized RCC were detected. CONCLUSIONS: It is encouraging that PN rates have increased in an eightfold fashion. Moreover, a fivefold increase was recorded for AS. These figures show a paradigm shift in the management of small renal masses. PMID- 22322957 TI - The role of tumor markers in the surgical approach of ovarian masses in pediatric age: a 10-year study and a literature review. AB - PURPOSE: The purpose of this study was to detect the role of serum tumor markers in the differential diagnosis and in the choice of the surgical treatment of ovarian lesions in pediatric age. METHODS: We retrospectively reviewed medical charts of all pediatric girls operated in two pediatric centers during a 10-year period. The following features were analyzed: age at the moment of presentation, symptoms, diagnostic studies, surgical approach, pathological findings, and, in particular, serum tumor markers. Also, a literature review and statistical analysis (chi(2) test) concerning the increase of different tumor markers in benign and malignant ovarian lesions were related to the study. RESULTS: A total of 120 children with 127 ovarian masses (7 with bilateral pathologies) were reviewed. Pathology showed 61 nonneoplastic lesions (48%), 54 benign tumors (42.5%), 5 malignant tumors (4%), and 7 torsed normal ovaries (5.5%). The evaluation of serum tumor markers was performed in 106 cases and was positive in 16 (15.1%): in all of the 5 cases (100%) of malignant neoplastic lesions and in 11 (20.4%) benign neoplastic ones. The literature review confirmed these data, and statistical analysis highlighted them as significant values. CONCLUSIONS: The role of tumor markers is still controversial. This is the reason why, before considering a radical treatment, we suggest caution to optimize future fertility. PMID- 22322958 TI - Interaction of environmental Burkholderia cenocepacia strains with cystic fibrosis and non-cystic fibrosis bronchial epithelial cells in vitro. AB - Burkholderia cenocepacia is an important human pathogen in patients with cystic fibrosis (CF). Non-clinical reservoirs may play a role in the acquisition of infection, so it is important to evaluate the pathogenic potential of environmental B. cenocepacia isolates. In this study, we investigated the interactions of two environmental B. cenocepacia strains (Mex1 and MCII-168) with two bronchial epithelial cell lines, 16HBE14o(-) and CFBE41o(-), which have a non CF and a CF phenotype, respectively. The environmental strains showed a significantly lower level of invasion into both CF and non-CF cells in comparison with the clinical B. cenocepacia LMG16656(T) strain. Exposure of polarized CFBE41o(-) or 16HBE14o(-) cells to the environmental strains resulted in a significant reduction in transepithelial resistance (TER), comparable with that observed following exposure to the clinical strain. A different mechanism of tight junction disruption in CF versus non-CF epithelia was found. In the 16HBE41o(-) cells, the environmental strains resulted in a drop in TER without any apparent effect on tight junction proteins such as zonula occludens-1 (ZO-1). In contrast, in CF cells, the amount of ZO-1 and its localization were clearly altered by the presence of both the environmental strains, comparable with the effect of LMG16656. This study demonstrates that even if the environmental strains are significantly less invasive than the clinical strain, they have an effect on epithelial integrity comparable with that of the clinical strain. Finally, the tight junction regulatory protein ZO-1 appears to be more susceptible to the presence of environmental strains in CF cells than in cells which express a functional cystic fibrosis transmembrane regulator (CFTR). PMID- 22322959 TI - In vivo features of signal transduction by the essential response regulator RpaB from Synechococcus elongatus PCC 7942. AB - The NblS-RpaB signalling pathway, the most conserved two-component system in cyanobacteria, regulates photosynthesis and acclimatization to a variety of environmental conditions and is involved in negative regulation of high-light induced genes. However, relevant regulatory details of the NblS-RpaB signalling pathway remain to be elucidated. We recently showed that the response regulator RpaB is regulated by specific (de)phosphorylation from the histidine kinase NblS and that RpaB and its phosphorylatable residue Asp56 are both required for viability of Synechococcus elongatus PCC 7942. We show here that the phosphorylated form of RpaB is present in cells growing under standard laboratory conditions and that high light stress affected the ratio of phosphorylated to non phosphorylated RpaB. It also decreased the amount of rpaB transcripts without appreciably changing the total levels of RpaB. Quantitative Western blotting and confocal microscopy analyses were consistent with RpaB being a very abundant regulator, with nucleoid localization. A genetically engineered RpaB-GFP (green fluorescent protein) fusion protein rescued lethality of the rpaB null mutant, indicating that it was functional. This is, to our knowledge, the first study demonstrating in a cyanobacterium, and for a two-component response regulator, that the in vivo ratio of phosphorylated to non-phosphorylated protein changes in response to environmental conditions. PMID- 22322960 TI - Proteomic and transcriptomic analysis of the response to bile stress of Lactobacillus casei BL23. AB - Lactobacillus casei is a lactic acid bacterium commonly found in the gastrointestinal tract of animals, and some strains are used as probiotics. The ability of probiotic strains to survive the passage through the gastrointestinal tract is considered a key factor for their probiotic action. Therefore, tolerance to bile salts is a desirable feature for probiotic strains. In this study we have characterized the response of L. casei BL23 to bile by a transcriptomic and proteomic approach. The analysis revealed that exposure to bile induced changes in the abundance of 52 proteins and the transcript levels of 67 genes. The observed changes affected genes and proteins involved in the stress response, fatty acid and cell wall biosynthesis, metabolism of carbohydrates, transport of peptides, coenzyme levels, membrane H(+)-ATPase, and a number of uncharacterized genes and proteins. These data provide new insights into the mechanisms that enable L. casei BL23 to cope with bile stress. PMID- 22322961 TI - Involvement of pnp in survival of UV radiation in Escherichia coli K-12. AB - Polynucleotide phosphorylase (PNPase), a multifunctional protein, is a 3'->5' exoribonuclease or exoDNase in the presence of inorganic phosphate (P(i)), and extends a 3'-OH of RNA or ssDNA in the presence of ADP or dADP. In Escherichia coli, PNPase is known to protect against H(2)O(2)- and mitomycin C-induced damage. Recent reports show that Bacillus subtilis PNPase is required for repair of H(2)O(2)-induced double-strand breaks. Here we show that absence of PNPase makes E. coli cells sensitive to UV, indicating that PNPase has a role in survival of UV radiation damage. Analyses of various DNA repair pathways show that in the absence of nucleotide excision repair, survival of UV radiation depends critically on PNPase function. Consequently, uvrA pnp, uvrB pnp and uvrC pnp strains show hypersensitivity to UV radiation. Whereas the pnp mutation is non-epistatic to recJ, recQ and recG mutations with respect to the UV-sensitivity phenotype, it is epistatic to uvrD, recB and ruvA mutations, implicating it in the recombinational repair process. PMID- 22322962 TI - Identification of C-terminal hydrophobic residues important for dimerization and all known functions of ParB of Pseudomonas aeruginosa. AB - The ParB protein of Pseudomonas aeruginosa is important for growth, cell division, nucleoid segregation and different types of motility. To further understand its function we have demonstrated a vital role of the hydrophobic residues in the C terminus of ParB(P.a.). By in silico modelling of the C terminal domain (amino acids 242-290) the hydrophobic residues L282, V285 and I289 (but not L286) are engaged in leucine-zipper-like structure formation, whereas the charged residues R290 and Q266 are implicated in forming a salt bridge involved in protein stabilization. Five parB mutant alleles were constructed and their functionality was defined in vivo and in vitro. In agreement with model predictions, the substitution L286A had no effect on mutant protein activities. Two ParBs with single substitutions L282A or V285A and deletions of two or seven C-terminal amino acids were impaired in both dimerization and DNA binding and were not able to silence genes adjacent to parS, suggesting that dimerization through the C terminus is a prerequisite for spreading on DNA. The defect in dimerization also correlated with loss of ability to interact with partner protein ParA. Reverse genetics demonstrated that a parB mutant producing ParB lacking the two C-terminal amino acids as well as mutants producing ParB with single substitution L282A or V285A had defects similar to those of a parB null mutant. Thus so far all the properties of ParB seem to depend on dimerization. PMID- 22322963 TI - Expression of budding yeast IPT1 produces mannosyldiinositol phosphorylceramide in fission yeast and inhibits cell growth. AB - In Saccharomyces (Sacc.) cerevisiae, the final step of the complex sphingolipid biosynthetic pathway requires Ipt1p for synthesis of mannosyldiinositol phosphorylceramide [M(IP)(2)C]. No fission yeast equivalent to Ipt1p has been found in the Schizosaccharomyces (Schiz.) pombe genome, and the most abundant complex sphingolipid is mannosylinositol phosphorylceramide. To examine the effect of expressing Sacc. cerevisiae IPT1 (ScIPT1) in Schiz. pombe, the ScIPT1 gene was cloned into an inducible fission yeast integrative vector and expressed in wild-type Schiz. pombe. In the Schiz. pombe ScIPT1-expressing cells, M(IP)(2)C was detected, indicating that ScIpt1p functions in M(IP)(2)C synthesis in Schiz. pombe. Expression of ScIPT1 caused pleiotropic phenotypes, including aberrant morphology and mislocalization of ergosterols in the plasma membrane. Furthermore, growth of Schiz. pombe was severely impaired. We analysed the sphingolipid composition of ScIPT1-expressing cells following a prolonged lag phase, and found that M(IP)(2)C was not synthesized, indicating that Ipt1p had been inactivated. GFP-tagged ScIpt1 localized primarily in the Golgi apparatus in wild-type Schiz. pombe. Over time, ScIpt1p was eventually transported to the vacuolar lumen through the multivesicular body pathway. These results indicate that M(IP)(2)C is toxic to Schiz. pombe and that fission yeast possesses an unknown mechanism to effectively extrude toxic sphingolipids from cells. PMID- 22322964 TI - Exploring the relationship between lipoprotein mislocalization and activation of the Rcs signal transduction system in Escherichia coli. AB - The Rcs phosphorelay signal transduction system controls genes for capsule production and many other envelope-related functions and is implicated in biofilm formation. We investigated the activation of the Rcs system in a pgsA null mutant of Escherichia coli, which completely lacks the major acidic phospholipids phosphatidylglycerol and cardiolipin. We found that the Rcs activation, and consequent thermosensitivity, were suppressed by overexpression of the lgt gene, encoding diacylglyceryltransferase, which catalyses the modification of prolipoproteins that is the first step in the maturation and localization process of lipoproteins, and is a prerequisite for the later steps. The outer-membrane lipoprotein RcsF is an essential component of Rcs signalling. This lipoprotein was poorly localized to the outer membrane in the pgsA null mutant, probably because of the absence of phosphatidylglycerol, the major donor of diacylglycerol in the Lgt reaction. Even in a pgsA(+) background, the Rcs system was activated when RcsF was mislocalized to the inner membrane by alteration of the residues at positions 2 and 3 of its mature form to inner-membrane retention signals, or when it was mislocalized to the periplasm by fusing the mature form to maltose-binding protein. These results suggest that RcsF functions as a ligand for RcsC in activating Rcs signalling. Mislocalized versions of RcsF still responded to mutations pgsA, mdoH and tolB, further activating the Rcs system, although the rfaP mutation barely caused activation. It seems that RcsF must be localized in the outer membrane to respond effectively to stimuli from outside the cell. PMID- 22322965 TI - The changes in chromosome 6 spatial organization during chromatin polytenization in the Calliphora erythrocephala Mg. (Diptera: Calliphoridae) nurse cells. AB - Localization of Calliphora erythrocephala chromosome 6 in a 3D nuclear space at different stages of nurse cell chromatin polytenization was analyzed by fluorescence in situ hybridization and 3D microscopy. The obtained results suggest a large-scale chromatin relocation in the C. erythrocephala nurse cell nuclei, which is accompanied by a change in the chromosome territory of chromosome 6 associated with the change in expression activity of the nucleus and formation of reticular chromatin structure. It was revealed that the relocation of chromosome 6 (nucleolus organizer chromosome) is accompanied by fragmentation of the single large nucleolus into micronucleoli, which are spread over the entire nuclear space being associated with their nucleolar organizer regions. Presumably, the chromosome 6 material during transition to a highly polytenized structure is redistributed in the nucleus so that the inactive pericentromeric regions are displaced to the nuclear periphery, while the chromosome regions carrying rDNA sequences loop out beyond the chromosome territory. Being dispersed over the entire nuclear space, rDNA sequences are likely to be amplified, thereby providing numerous small signals from the chromosome 6-specific DNA probe. Micronucleoli are formed around the actively transcribed nucleolar organizer regions. PMID- 22322966 TI - Effects of crystalloid versus colloid and the alpha-2 agonist brimonidine versus placebo on intraocular pressure during prone spine surgery: a factorial randomized trial. AB - BACKGROUND: Volume replacement with colloid solution and topical alpha-2 agonists may each moderate the progressive increase in intraocular pressure (IOP) during prone surgery. The authors tested the hypotheses that during prolonged prone surgery, IOP increases less with goal-directed intravenous administration of 5% albumin than with goal-directed administration of lactated Ringer's solution, and with topical alpha-2 agonist brimonidine than with placebo eye drops. METHODS: Patients having complex prone spine surgery were factorially randomized to albumin and topical placebo (n = 15); albumin and topical brimonidine (n = 16); lactated Ringer's solution and topical placebo (n = 13); and lactated Ringer's solution and topical brimonidine (n = 16). IOP was measured with a pneumotonometer. The primary outcome was time-weighted average intraoperative IOP. RESULTS: Prone positioning increased IOP a mean +/- SD of 12 +/- 6 mmHg. IOP increased to 38 +/- 10 mmHg at the end of anesthesia (approximately 5.5 h). Time- weighted average intraoperative IOP in the brimonidine group was 4 (95% CI: 1, 8) mmHg lower than in the placebo group (P = 0.023), but no different in the crystalloid and albumin groups (mean difference (95% CI) of -2 (-5, 2) mmHg (P = 0.34). There was no interaction between the two randomized factors. CONCLUSIONS: Brimonidine slightly reduced the primary outcome of intraoperative time-weighted average IOP, whereas there was no significant difference between goal-directed albumin or crystalloid administration. Brimonidine thus helps reduce IOP during spine surgery, but maintaining adequate blood pressure might play a more important role. PMID- 22322967 TI - Organic photovoltaic devices with colloidal TiO2 nanorods as key functional components. AB - We report on a novel approach to integrate colloidal anatase TiO(2) nanorods as key functional components into polymer bulk heterojunction (BHJ) photovoltaic devices by means of mild, all-solution-based processing techniques. The successful integration of colloidal nanoparticles in organic solar cells relies on the ability to remove the long chain insulating ligands, which indeed severely reduces the charge transport. To this aim we have exploited the concomitant mechanisms of UV-light-driven photocatalytic removal of adsorbed capping ligands and hydrophilicization of TiO(2) surfaces in both solid-state and liquid-phase conditions. We have demonstrated the successful integration of the UV-irradiated films and colloidal solutions of TiO(2) nanorods in inverted and conventional solar cell geometries, respectively. The inverted devices show a power conversion efficiency of 2.3% that is a ca. three times improvement over their corresponding cell counterparts incorporating untreated TiO(2), demonstrating the excellent electron-collecting property of the UV-irradiated TiO(2) films. The integration of UV-treated TiO(2) solutions in conventional devices results in doubled power conversion efficiency for the thinner active layer and in maximum power conversion efficiency of 2.8% for 110 nm thick devices. In addition, we have demonstrated, with the support of device characterizations and optical simulations, that the TiO(2) nanocrystal buffer layer acts both as electron transporting/hole-blocking material and optical spacer. PMID- 22322968 TI - The peritoneal tumour microenvironment of high-grade serous ovarian cancer. AB - High-grade serous ovarian cancer (HGSC) disseminates early and extensively throughout the peritoneal space, causing multiple lesions that are a major clinical problem. The aim of this study was to investigate the cellular composition of peritoneal tumour deposits in patient biopsies and their evolution in mouse models using immunohistochemistry, intravital microscopy, confocal microscopy, and 3D modelling. Tumour deposits from the omentum of HGSC patients contained a prominent leukocyte infiltrate of CD3(+) T cells and CD68(+) macrophages, with occasional neutrophils. Alpha-smooth muscle actin(+) (alpha SMA(+) ) pericytes and/or fibroblasts surrounded these well-vascularized tumour deposits. Using the murine bowel mesentery as an accessible mouse peritoneal tissue that could be easily imaged, and two different transplantable models, we found multiple microscopic tumour deposits after i.p. injection of malignant cells. Attachment to the peritoneal surface was rapid (6-48 h) with an extensive CD45(+) leukocyte infiltrate visible by 48 h. This infiltrate persisted until end point and in the syngeneic murine ID8 model, it primarily consisted of CD3(+) T lymphocytes and CD68(+) macrophages with alpha-SMA(+) cells also involved from the earliest stages. A majority of tumour deposits developed above existing mesenteric blood vessels, but in avascular spaces new blood vessels tracked towards the tumour deposits by 2-3 weeks in the IGROV-1 xenografts and 6 weeks in the ID8 syngeneic model; a vigorous convoluted blood supply was established by end point. Inhibition of tumour cell cytokine production by stable expression of shRNA to CXCR4 in IGROV-1 cells did not influence the attachment of cells to the mesentery but delayed neovascularization and reduced tumour deposit size. We conclude that the multiple peritoneal tumour deposits found in HGSC patients can be modelled in the mouse. The techniques described here may be useful for assessing treatments that target the disseminated stage of this disease. PMID- 22322969 TI - Modulations in restricted amide rotation by steric induced conformational trapping. AB - The rotation around the amide bond in N,N-diethyl-m-toluamide (m-DEET) has been studied extensively and often used in laboratory instructions to demonstrate the phenomenon of chemical exchange. Herein, we show that a simple modification to N,N-diethyl-o-toluamide (o-DEET) significantly alters the dynamics of the restricted rotation around the amide bond due to steric interactions between the ring methyl group and the two N-ethyl groups. This alters the classic two-site exchange due to restricted rotation around the amide bond, to a three-site exchange, with the third conformation trapped at a higher-energy state compared to the other two. This often overlooked phenomenon is elucidated using variable temperature NMR, two-dimensional exchange spectroscopy and molecular modeling studies. PMID- 22322970 TI - Aldosterone induces active K+ secretion by enhancing mucosal expression of Kcnn4c and Kcnma1 channels in rat distal colon. AB - Although both Kcnn4c and Kcnma1 channels are present on colonic mucosal membranes, only Kcnma1 has been suggested to mediate K(+) secretion in the colon. Therefore, studies were initiated to investigate the relative roles of Kcnn4c and Kcnma1 in mediating aldosterone (Na-free diet)-induced K(+) secretion. Mucosal to serosal (m-s), serosal to mucosal (s-m), and net (86)Rb(+) (K(+) surrogate) fluxes as well as short circuit currents (I(sc); measure of net ion movement) were measured under voltage clamp condition in rat distal colon. Active K(+) absorption, but not K(+) secretion, is present in normal, while aldosterone induces active K(+) secretion (1.04 +/- 0.26 vs. -1.21 +/- 0.15 MUeq.h(-1).cm( 2); P < 0.001) in rat distal colon. Mucosal VO(4) (a P-type ATPase inhibitor) inhibited the net K(+) absorption in normal, while it significantly enhanced net K(+) secretion in aldosterone animals. The aldosterone-induced K(+) secretion was inhibited by the mucosal addition of 1) either Ba(2+) (a nonspecific K(+) channel blocker) or charybdotoxin (CTX; a common Kcnn4 and Kcnma1 channel blocker) by 89%; 2) tetraethyl ammonium (TEA) or iberiotoxin (IbTX; a Kcnma1 channel blocker) by 64%; and 3) TRAM-34 (a Kcnn4 channel blocker) by 29%. TRAM-34, but not TEA, in the presence of IbTX further significantly inhibited the aldosterone-induced K(+) secretion. Thus the aldosterone-induced Ba(2+)/CTX-sensitive K(+) secretion consists of IbTX/TEA-sensitive (Kcnma1) and IbTX/TEA-insensitive fractions. TRAM 34 inhibition of the IbTX-insensitive fraction is consistent with the aldosterone induced K(+) secretion being mediated partially via Kcnn4c. Western and quantitative PCR analyses indicated that aldosterone enhanced both Kcnn4c and Kcnma1alpha protein expression and mRNA abundance. In vitro exposure of isolated normal colonic mucosa to aldosterone also enhanced Kcnn4c and Kcnma1alpha mRNA levels, and this was prevented by exposure to actinomycin D (an RNA synthesis inhibitor). These observations indicate that aldosterone induces active K(+) secretion by enhancing mucosal Kcnn4c and Kcnma1 expression at the transcriptional level. PMID- 22322971 TI - Nitric oxide and voluntary exercise together promote quadriceps hypertrophy and increase vascular density in female 18-mo-old mice. AB - Age-related sarcopenia reduces the size, strength, and function of muscle, and the diameter of muscle fibers. It also disrupts the dystrophin-glycoprotein complex, dislocating nitric oxide synthase 1 (NOS-1) and reducing sarcolemmal integrity. This study of quadriceps muscle in 18-mo-old mice showed that NO-donor treatment with isosorbide dinitrate (I) for 6 wk, in combination with voluntary exercise for 3 wk, increased muscle mass by 25% and stimulated cell proliferation. The resulting fiber hypertrophy was accompanied by a lower ratio of protein:DNA, consistent with myogenic-cell hyperplasia. Treatment enhanced the ratio of NOS-1:beta-dystroglycan in correlation with fiber diameter, improved sarcolemmal integrity, and increased vascular density after an increase in vascular endothelial growth factor protein at 3 wk. Results demonstrate that age related muscle refractoriness to exercise can be overcome with NO-donor treatment. Since activation of muscle stem cells and vascular perfusion are limiting factors in the maintenance, regeneration, and growth of aged muscle, results suggest the feasibility of using NO-donor drugs to combat atrophy and muscle ischemia. Improved function and quality of life from the NO-amplified effects of exercise may be useful in aging and other conditions such as disuse, insulin resistance, or microgravity. PMID- 22322972 TI - Impaired insulin-stimulated myosin phosphatase Rho-interacting protein signaling in diabetic Goto-Kakizaki vascular smooth muscle cells. AB - Insulin resistance associated with Type 2 diabetes contributes to impaired vasorelaxation and therefore contributes to the enhanced incidence of hypertension observed in diabetes. In this study, we examined the role of insulin on the association of the myosin-binding subunit of myosin phosphatase (MYPT1) to myosin phosphatase Rho-interacting protein (MRIP), a relatively novel member of the myosin phosphatase complex that directly binds RhoA in vascular smooth muscle cells (VSMCs). Through a series of molecular and cellular studies, we investigated whether insulin stimulates the binding of MRIP to MYPT1 and compared the results generated from VSMCs isolated from both Wistar-Kyoto (WKY) control and Goto-Kakizaki (GK) diabetic rats. We demonstrate for the first time that insulin stimulates the binding of MRIP to MYPT1 in a dose- and time-dependent manner, as determined by immunoprecipitation, implying a regulatory role for MRIP in insulin-induced vasodilation signaling via MYPT1 interaction. VSMCs from GK model of Type 2 diabetes had impaired insulin-induced MRIP/MYPT1 binding as well as reduced MRIP expression. Adenovirus-mediated overexpression of MRIP in GK VSMCs led to significantly improved insulin-stimulated MRIP/MYPT1 binding. Finally, insulin-stimulated MRIP translocation out of stress fibers, which was observed in control VSMCs, was impaired in GK VSMCs. We believe the impaired expression of MRIP, and therefore decreased insulin-stimulated MRIP/MYPT1 association, in the GK diabetic model may contribute to the impaired insulin mediated vasodilation observed in the diabetic vasculature and provides a novel therapeutic strategy for the treatment of Type 2 diabetes. PMID- 22322973 TI - Inhibition of phosphodiesterases relaxes detrusor smooth muscle via activation of the large-conductance voltage- and Ca2+-activated K+ channel. AB - Detrusor smooth muscle (DSM) exhibits increased spontaneous phasic contractions under pathophysiological conditions such as detrusor overactivity (DO). Our previous studies showed that activation of cAMP signaling pathways reduces DSM contractility by increasing the large-conductance voltage- and Ca(2+)-activated K(+) (BK) channel activity. Here, we tested the hypothesis whether inhibition of phosphodiesterases (PDEs) can reduce guinea pig DSM excitability and contractility by increasing BK channel activity. Utilizing isometric tension recordings of DSM isolated strips and the perforated patch-clamp technique on freshly isolated DSM cells, we examined the mechanism of DSM relaxation induced by PDE inhibition. Inhibition of PDEs by 3-isobutyl-1-methylxanthine (IBMX), a nonselective PDE inhibitor, significantly reduced DSM spontaneous and carbachol induced contraction amplitude, frequency, duration, muscle force integral, and tone in a concentration-dependent manner. IBMX significantly reduced electrical field stimulation-induced contractions of DSM strips. Blocking BK channels with paxilline diminished the inhibitory effects of IBMX on DSM contractility, indicating a role for BK channels in DSM relaxation mediated by PDE inhibition. IBMX increased the transient BK currents (TBKCs) frequency by ~3-fold without affecting the TBKCs amplitude. IBMX increased the frequency of the spontaneous transient hyperpolarizations by ~2-fold and hyperpolarized the DSM cell resting membrane potential by ~6 mV. Blocking the BK channels with paxilline abolished the IBMX hyperpolarizing effects. Under conditions of blocked Ca(2+) sources for BK channel activation, IBMX did not affect the depolarization-induced steady state whole cell BK currents. Our data reveal that PDE inhibition with IBMX relaxes guinea pig DSM via TBKCs activation and subsequent DSM cell membrane hyperpolarization. PMID- 22322974 TI - Repression of PDGF-R-alpha after cellular injury involves TNF-alpha, formation of a c-Fos-YY1 complex, and negative regulation by HDAC. AB - Wound healing is a complex dynamic process involving a variety of cell types, including fibroblasts that express and respond to cytokines and growth factors in the local microenvironment. The mechanisms controlling gene expression after injury at a transcriptional level are poorly understood. Here we show that decreased expression of a key receptor, PDGF-receptor (R)-alpha, after fibroblast injury is due to the release and paracrine activity of TNF-alpha. TNF-alpha inhibits PDGF-R-alpha expression and this involves formation of a c-Fos-Yin Yang 1 (YY1) complex and histone deacetylase (HDAC) activity. c-Fos, induced by TNF alpha, negatively regulates PDGF-R-alpha transcription. Small interfering RNA (siRNA) targeting c-Fos or the zinc finger transcription factor YY1 inhibits TNF alpha suppression of PDGF-R-alpha expression. Coimmunoprecipitation studies show that TNF-alpha stimulates the formation of a complex between c-Fos with YY1. Furthermore, chromatin immunoprecipitation (ChIP) analysis reveals the enrichment of c-Fos, YY1, and HDAC-1 at the PDGF-R-alpha promoter in cells exposed to TNF alpha. With suberoylanilide hydroxamic acid (SAHA) and HDAC-1 siRNA, we demonstrate that HDAC mediates TNF-alpha repression of PDGF-R-alpha. These findings demonstrate that transcriptional repression of PDGF-R-alpha after fibroblast injury involves paracrine activity of endogenous TNF-alpha, the formation of a c-Fos-YY1 complex, and negative regulatory activity by HDAC. PMID- 22322975 TI - RhoA guanine exchange factor expression profile in arteries: evidence for a Rho kinase-dependent negative feedback in angiotensin II-dependent hypertension. AB - Sustained overactivation of RhoA is a common component for the pathogenesis of several cardiovascular disorders, including hypertension. Although activity of Rho proteins depends on Rho exchange factors (Rho-GEFs), the identity of Rho-GEFs expressed in vascular smooth muscle cells (VSMC) and participating in the control of Rho protein activity and Rho-dependent functions remains unknown. To address this question, we analyzed by quantitative RT-PCR the expression profile of 28 RhoA-GEFs in arteries of normotensive (saline-treated) and hypertensive (ANG II treated) rats. Sixteen RhoA-GEFs were downregulated in mesenteric arteries of hypertensive rats, among which nine are also downregulated in cultured VSMC stimulated by ANG II (100 nM, 48 h), suggesting a direct effect of ANG II. Inhibition of type 1 ANG II receptors (losartan, 1 MUM) or Rho kinase (fasudil, 10 MUM) prevented ANG II-induced RhoA-GEF downregulation. Functionally, ANG II induced downregulation of RhoA-GEFs is associated with decreased Rho kinase activation in response to endothelin-1, norepinephrine, and U-46619. This work thus identifies a group of RhoA-GEFs that controls RhoA and RhoA-dependent functions in VSMC, and a negative feedback of RhoA/Rho kinase activity on the expression of these RhoA-GEFs that may play an adaptative role to limit RhoA/Rho kinase activation. PMID- 22322976 TI - Thyroid hormone receptor-alpha and vascular function. AB - Thyroid hormone (TH) treatment exerts beneficial effects on the cardiovascular system: it lowers cholesterol and LDL levels and enhances cardiac contractile function. However, little is known about the effect of TH on vascular function or the functional role of TH receptors (TRs) in the regulation of vascular tone. We have investigated the contribution of TRs to vascular contractility in the heart. Among different TR subtype-specific knockout (KO) mice, vascular contraction was significantly enhanced in coronary arteries isolated from TRalpha KO compared with wild-type mice, while chronic TH treatment significantly attenuated coronary vascular contraction. We found that TRalpha is the predominant TR in mouse coronary smooth muscle cells (SMCs). Coronary SMCs isolated from TRalpha KO mice exhibited a significant decrease in K(+) channel activity, whereas TH treatment increased K(+) channel activity in a dose-dependent manner. These data suggest that TRalpha in SMCs has prominent effects on regulation of vascular tone and TH treatment helps decrease coronary vascular tone by increasing K(+) channel activity through TRalpha in SMCs. PMID- 22322977 TI - Hydrogen peroxide mediates oxidant-dependent stimulation of arterial smooth muscle L-type calcium channels. AB - Changes in calcium and redox homeostasis influence multiple cellular processes. Dysregulation of these signaling modalities is associated with pathology in cardiovascular, neuronal, endocrine, and other physiological systems. Calcium and oxidant signaling mechanisms are frequently inferred to be functionally related. To address and clarify this clinically relevant issue in the vasculature we tested the hypothesis that the ubiquitous reactive oxygen molecule hydrogen peroxide mediates oxidant-dependent stimulation of cerebral arterial smooth muscle L-type calcium channels. Using a combinatorial approach including intact arterial manipulations, electrophysiology, and total internal reflection fluorescence imaging, we found that application of physiological levels of hydrogen peroxide to isolated arterial smooth muscle cells increased localized calcium influx through L-type calcium channels. Similarly, oxidant-dependent stimulation of L-type calcium channels by the vasoconstrictor ANG II was abolished by intracellular application of catalase. Catalase also prevented ANG II from increasing localized subplasmalemmal sites of increased oxidation previously associated with colocalized calcium influx through L-type channels. Furthermore, catalase largely attenuated the contractile response of intact cerebral arterial segments to ANG II. In contrast, enhanced dismutation of superoxide to hydrogen peroxide with SOD had no effect on ANG II-dependent stimulation of L-type calcium channels. From these data we conclude that hydrogen peroxide is important for oxidant-dependent regulation of smooth muscle L-type calcium channels and arterial function. These data also support the emerging concept of hydrogen peroxide as a biologically relevant oxidant second messenger in multiple cell types with a diverse array of physiological functions. PMID- 22322978 TI - Understanding the mechanisms that link alcohol and lower risk of coronary heart disease. PMID- 22322979 TI - Personalized cancer genomics: the road map to clinical implementation. PMID- 22322980 TI - Seven reasons not to be a peer reviewer--and why these reasons are wrong. PMID- 22322981 TI - Novel strategies in the treatment of castration-resistant prostate cancer (Review). AB - Prostate cancer is the most common cancer in men in Europe and the United States, and the third leading cause of death from cancer in Europe. Survival of prostate cancer cells is dependent on the activation of androgen receptors (AR), that are overexpressed in this tumor. Furthermore, ~90% of prostate cancer patients that respond to first-line androgen deprivation therapy (ADT) undergo rapid progression. This condition is defined as castration-resistant prostate cancer (CRPC). Docetaxel-based regimens significantly improve overall survival (OS) in patients with CRPC and represent the only treatment strategy approved by the Food and Drug Administration (FDA). Recently, abiraterone (second hormonal therapy) and cabazitaxel (new taxane) have been shown to improve survival in patients with CRPC who progressed following docetaxel-based chemotherapy. Vaccine therapy has also been demonstrated to improve OS in patients with asymptomatic or minimally symptomatic metastatic CRPC. Additional therapeutic targets have been analyzed in prostate cancer, including apoptosis, angiogenic receptors, vitamin D and Src pathways. Several phase II studies are ongoing. The high frequency of prostate cancer-related metastatic bone disease has led to consider this pathway as a therapeutic target. To this end, several bone-targeted agents have been investigated, most notably zoledronic acid, which is highly effective at stabilizing the bone and preventing skeletal complications. More recently, a nuclear factor-beta ligand (RANKL) inhibitor, denosumab, has been developed for the treatment of bone metastases. PMID- 22322982 TI - Health care access and treatment for children with co-morbid autism and psychiatric conditions. AB - PURPOSE: To characterize the rate of comorbid psychiatric conditions (CPC) among children with autism spectrum disorders (ASD), to examine their treatment utilization, and to investigate treatment delay or non-delivery. METHODS: Lifetime ASD and CPC in children, aged 2-17, were investigated using data from the 2007-2008 National Survey of Children's Health (NSCH). The NSCH surveyed parents and guardians regarding the health and well being, including treatment, of their child(ren) under age 18 (n = 91,642). Children with health conditions were defined by parent report that a doctor or other health professional had ever said their child had that condition. Factors related to overall health, treatment utilization, and barriers to access variables were investigated among this group. RESULTS: Children with ASD/CPC had poorer overall health outcomes than children with ASD alone. They more often were dissatisfied with their between-provider communication and less often had insurance cover needed services. Nonetheless, they did tend to use care coordination and mental health services to a greater degree. Families were more likely to report the delay or non-receipt of needed services when they perceived a lack of communication and partnership with providers, when they lacked insurance coverage, and when they felt that health care costs were unreasonable. CONCLUSIONS: The presence of a CPC seems to shape the treatment utilization and health outcomes of children with ASD. Because of this, health professionals working with children with autism should give special attention to treatment of those with comorbid diagnoses. PMID- 22322983 TI - Measures of the recovery orientation of mental health services: systematic review. AB - PURPOSE: The review aimed to (1) identify measures that assess the recovery orientation of services; (2) discuss how these measures have conceptualised recovery, and (3) characterise their psychometric properties. METHODS: A systematic review was undertaken using seven sources. The conceptualisation of recovery within each measure was investigated by rating items against a conceptual framework of recovery comprising five recovery processes: connectedness; hope and optimism; identity; meaning and purpose; and empowerment. Psychometric properties of measures were evaluated using quality criteria. RESULTS: Thirteen recovery orientation measures were identified, of which six met eligibility criteria. No measure was a good fit with the conceptual framework. No measure had undergone extensive psychometric testing and none had data on test retest reliability or sensitivity to change. CONCLUSIONS: Many measures have been developed to assess the recovery orientation of services. Comparisons between the measures were hampered by the different conceptualisations of recovery used and by the lack of uniformity on the level of organisation at which services were assessed. This situation makes it a challenge for services and researchers to make an informed choice on which measure to use. Further work is needed to produce measures with a transparent conceptual underpinning and demonstrated psychometric properties. PMID- 22322984 TI - Comparative pharmacokinetics of senkyunolide I in a rat model of migraine versus normal controls. AB - Senkyunolide I is an active ingredient of Rhizoma Chuanxiong, a Chinese medicinal herb commonly used for the treatment of cardiovascular ailments. In the present paper, we describe the isolation and elucidation of senkyunolide I from the ethanol extract of Rhizoma Chuanxiong and its pharmacokinetic behavior after intravenous and oral administration to normal and migrainous rats. After intravenous administration, senkyunolide I was rapidly distributed (V ( z )/F 2.07 +/- 0.43 L/kg) and eliminated from the plasma (CL( z ) 2.56 +/- 0.29 L/h/kg and t (1/2z ) 0.56 +/- 0.13 h). After administration orally to normal rats at two dosages (20 and 72 mg/kg), the pharmacokinetic parameters of senkyunolide I were as follows: T (max) 0.25 +/- 0.06 and 0.38 +/- 0.11 h, C (max) 5,236.3 +/- 802.8 and 22,071.9 +/- 3,456.1 mg/L, Area under the curve(AUC)((0-t)) 5,217.5 +/- 1,029.5 and 21,480.2 +/- 3,003.1 MUg h/L, respectively. Its oral absolute bioavailability at the two dosages was 67.2 and 76.9%, respectively. Intriguingly, migraine caused some significant changes in its pharmacokinetic parameter. For example, when compared with its pharmacokinetic behavior in normal rats at the two dosages, on average, its clearance decreased by 68% and volume of distribution increased by 342% in migrainous rats, both of which contributed to its several-fold increase in t (1/2z) and AUC. C (max) and AUC of senkyunolide I increased almost proportionally with dose between 20 and 72 mg/kg and the pharmacokinetics fit linear kinetic feature. The pharmacokinetic parameters of senkyunolide I were significantly different in normal and migrainous rats, which should be taken into account during the design of a clinical dosage regimen for senkyunolide I. PMID- 22322985 TI - Rhynchophylline attenuates LPS-induced pro-inflammatory responses through down regulation of MAPK/NF-kappaB signaling pathways in primary microglia. AB - Excessive activation of microglial cells has been implicated in various types of neuroinflammation. Suppression of microglial activation would have therapeutic benefits, leading to the alleviation of the progression of neurodegeneration. In this study, the inhibitory effects of rhynchophylline (RIN), a tetracyclic oxindole alkaloid component isolated from Uncaria rhynchophylla (Miq.) Jacks., on the production of pro-inflammatory mediators were investigated in lipopolysaccharide (LPS)-stimulated microglia. The results showed that RIN markedly reduced the production of nitric oxide (NO), prostaglandins E(2) (PGE(2) ), monocyte chemoattractant protein (MCP-1), tumor necrosis factor-alpha (TNF alpha) and interleukin-1beta (IL-1beta) in LPS-activated microglia. The mRNA expression levels of iNOS and COX-2 were also depressed by RIN in a concentration dependent manner. Further studies revealed that RIN blocked IkappaBalpha phosphorylation and degradation, inhibited the phosphorylation of mitogen activated protein kinases (MAPKs). In summary, these data suggest that RIN suppresses inflammatory responses of microglia and may act as a potential therapeutic agent for various neurodegenerative diseases involving neuroinflammation. PMID- 22322986 TI - Illness beliefs and treatment beliefs as predictors of short and middle term outcome in depression. AB - The article investigates whether illness beliefs and beliefs about rehabilitation are predictors of short and middle term outcome in depression even when adjustments are made for variables, which are known to be predictors of the course of depression. Within the context of a non-controlled prospective study design, data were analyzed using forced entry hierarchical multiple regression analyses. The sample comprised N = 98 patients. Adjusting for a range of sociodemographic and medical predictors, illness beliefs and beliefs about rehabilitation predict outcome in depression. Illness beliefs and beliefs about rehabilitation are relevant starting points for designing patient-oriented interventions. PMID- 22322987 TI - Words about body and soul: social representations relating to health and illness. AB - The purpose was to examine a sample of Stockholm residents' social representations of their physical and mental health and ill-health. Four open ended questions were answered by 1240 people between 18-80 years. A thematic analysis revealed nine aspects of health: physical, lifestyle, psychological, social, recreational, work and study, treatment, other and multifactorial aspects. Some cross-cutting themes were described to have an impact on health: empowerment, health-conscious lifestyle, life balance and life perspective. A key result is the interdependence between physical and mental health that was described by the respondents. PMID- 22322988 TI - Lateralized goal framing: how selective presentation impacts message effectiveness. AB - We tested whether framing a message as a gain or loss would alter its effectiveness by using a dichotic listening procedure to selectively present a health related message to the left or right hemisphere. A significant goal framing effect (losses > gains) was found when right, but not left, hemisphere processing was initially enhanced. The results support the position that the contextual processing style of the right hemisphere is especially sensitive to the associative implications of the frame. We discussed the implications of these findings for goal framing research, and the valence hypothesis. We also discussed how these findings converge with prior valence framing research and how they can be of potential use to health care providers. PMID- 22322989 TI - 6 x 40 mins exercise improves body image, even though body weight and shape do not change. AB - Body weight, shape and body image were assessed in 16 males and 18 females before and after both 6 x 40 mins exercise and 6 x 40 mins reading. Over both conditions, body weight and shape did not change. Various aspects of body image, however, improved after exercise compared to before, while no changes were found over reading. These findings have implications for exercise promotion where a possible role for body image in exercise adherence is suggested, and confirm current theories of body image, where changes in body image are mediated by body perceptions as opposed to actual body indices. PMID- 22322990 TI - Depression among the urban poor in Peninsular Malaysia: a community based cross sectional study. AB - This community based cross-sectional study examined the prevalence and factors associated with depression among urban poor in Peninsular Malaysia. The Patient Health Questionnaire (PHQ-9) was used to determine the presence or absence of depression. The prevalence of depression among the urban poor was 12.3%. Factors significantly associated with depression included respondents under 25 years old, male gender, living in the area for less than four years and those who do not exercise regularly. It is important to identify individuals with depression and its associated factors early because depression can severely affect the quality of life. PMID- 22322991 TI - Effectiveness of a play-integrated primary one preparatory programme to enhance a smooth transition for children. AB - This study tested the effectiveness of a play-integrated preparatory programme to enhance a smooth transition for children from kindergarten to primary one. A randomized controlled trial was employed and 142 families were recruited. Children in the experimental group experienced greater happiness, fewer worries and lesser difficulty in psychological adjustment than children in the control group, providing evidence that the play-integrated preparatory programme is effective in enhancing a smooth transition for children. Findings from this study promote the awareness in parents and teachers that play is an important part of children's lives, which is essential for their normal growth and development. PMID- 22322992 TI - Gifts of giving: the role of empathy and perceived benefits to others and self in young adults' decisions to become organ donors. AB - Trait empathy and self-interest exert a strong influence on different prosocial behaviors, but their role in the promotion of organ donation registration is unclear. A survey examined how perceived benefits of organ donation for others and the self affect people's willingness to register as donors. Perceived other benefits did not predict registration. Those with lower risk and greater self benefit perceptions were more willing to donate. Empathic concern predicted donation willingness and moderated the effect of other-benefit perceptions, such that other-benefit perceptions predicted donation willingness among those with greater empathic concern. Applications of these findings to organ donation promotion are discussed. PMID- 22322993 TI - A prognostic gene expression signature in infratentorial ependymoma. AB - Patients with ependymoma exhibit a wide range of clinical outcomes that are currently unexplained by clinical or histological factors. Little is known regarding molecular biomarkers that could predict clinical behavior. Since recent data suggest that these tumors display biological characteristics according to their location (cerebral vs. infratentorial vs. spinal cord), rather than explore a broad spectrum of ependymoma, we focused on molecular alterations in ependymomas arising in the infratentorial compartment. Unsupervised clustering of available gene expression microarray data revealed two major subgroups of infratentorial ependymoma. Group 1 tumors over expressed genes that were associated with mesenchyme, Group 2 tumors showed no distinct gene ontologies. To assess the prognostic significance of these gene expression subgroups, real-time reverse transcriptase polymerase chain reaction assays were performed on genes defining the subgroups in a training set. This resulted in a 10-gene prognostic signature. Multivariate analysis showed that the 10-gene signature was an independent predictor of recurrence-free survival after adjusting for clinical factors. Evaluation of an external dataset describing subgroups of infratentorial ependymomas showed concordance of subgroup definition, including validation of the mesenchymal subclass. Importantly, the 10-gene signature was validated as a predictor of recurrence-free survival in this dataset. Taken together, the results indicate a link between clinical outcome and biologically identified subsets of infratentorial ependymoma and offer the potential for prognostic testing to estimate clinical aggressiveness in these tumors. PMID- 22322994 TI - Commensal gut flora and brain autoimmunity: a love or hate affair? AB - Multiple sclerosis (MS) and other chronic inflammatory autoimmune diseases represent major public health challenges in industrialised Western society. MS results from an autoimmune attack against myelin structures by self-reactive lymphocytes, which are normal components of the healthy immune repertoire. The nature of the triggers that convert the innocuous self-reactive lymphocytes into an autoaggressive phenotype is poorly understood. In the past, it was primarily suspected that pathogenic infections trigger MS. However, so far, none of the incriminated pathogenic microbes were firmly associated with the disease. A growing body of evidence in animal models of MS implicates the gut microbiota in the induction of central nervous system (CNS) autoimmunity. The mammalian gut harbors a diverse population of microbial organisms which are essential for our well being. There is an increasing understanding that the gut microbiota not only modulates the local immune functions but also affects the systemic immune system. We are only just beginning to understand the nature of the interactions of the gut microbiota with the host's immune system especially in the context of autoimmune diseases. This review will address the influence of intestinal microbiota on immune homeostasis and on the development of autoimmune responses at sites distal to the intestine with a particular emphasis placed on a discussion about CNS autoimmunity. PMID- 22322995 TI - Lamotrigine in the treatment of unipolar depression with and without comorbidities: a literature review. AB - To review the available data behind the use of lamotrigine in unipolar depression and common comorbid conditions. A PubMed based literature review was conducted using keywords related to lamotrigine, depression, anxiety, post traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and personality disorders. A large number of trials using lamotrigine for unipolar depression and various comorbid conditions were reviewed. A major limitation behind the majority of studies was a limited course of the treatment phase. The most robust data was found among studies that followed patients for over 8 weeks, and used higher dosages. Patients with comorbid anxiety states appeared to benefit. Patients with borderline personality disorder also appeared to benefit. The benefits of lamotrigine in unipolar depression have been inconsistently noted in a number of studies. This is due in part to short treatment phases, atypical domains of benefit and different patient populations across studies. Patients with more treatment-resistance, comorbid anxiety and borderline personality disorder may be more able to benefit from lamotrigine. PMID- 22322996 TI - Large variations in the magnetic ordering behavior of EuCu(2)As(2) with the application of external pressure and magnetic field. AB - The influence of external pressure on the electrical transport and magnetic properties of EuCu(2)As(2), crystallizing in a ThCr(2)Si(2)-type structure, is reported. The system is known to be an antiferromagnet below T(N) ~ 15 K in the absence of external magnetic fields. We find that there is a gradual reduction of T(N) with the application of a magnetic field with an extrapolated value of the critical field of around 18 kOe which can drive T(N) to zero. Electrical resistivity under pressure (<11 GPa) reveals that the magnetic ordering temperature is pushed up dramatically to higher temperatures which is quite interesting if compared with the behavior in isostructural FeAs-based systems containing Eu. Above 7 GPa, the pressure-induced state appears to be ferromagnetic. The results thus reveal interesting changes in the magnetic ordering behavior of this compound with increasing pressure and magnetic fields. PMID- 22322997 TI - Idiopathic isolated orbicularis weakness. AB - PURPOSE: Orbicularis weakness is commonly associated with seventh nerve palsy or neuromuscular and myopathic conditions such as myotonic dystrophy and myasethenia gravis. We report four cases of idiopathic isolated orbicularis weakness. METHODS: All four cases were female and the presenting symptoms of ocular irritation and epiphora had been present for over 7 years in three patients. All patients had lagophthalmos and three had ectropion. Three patients underwent full investigations which excluded known causes of orbicularis weakness. Two patients underwent oribularis oculi muscle biopsy and histological confirmation of orbicularis atrophy. RESULTS: All patients underwent surgery to specifically address the orbicularis weakness with satisfactory outcomes and alleviation of symptoms in all cases. Isolated orbicularis weakness may be a relatively common entity that is frequently overlooked. CONCLUSION: Early recognition of this condition may lead to better management and prevent patients undergoing unnecessary surgical procedures. PMID- 22322998 TI - Microperimetric changes in neovascular age-related macular degeneration treated with ranibizumab. AB - PURPOSE: To assess the value of microperimetry in eyes with neovascular age related macular degeneration previously treated with ranibizumab and now in the maintenance phase of therapy. METHODS: A total of 21 eyes (14 patients) were included. Microperimetry was performed using the Macular Integrity Assessment Device on at least three occasions for each eye. Intravitreal ranibizumab was administered if visual acuity (VA) or optical coherence tomography (OCT) showed signs of active disease. RESULTS: Five eyes showed no change in VA or OCT findings, and required no intravitreal injections. In these eyes, mean threshold sensitivity (TS) decreased by 13% (paired t-test, P=0.05) during the study period, but fixation stability (FS) was unchanged. In all, 16 eyes showed signs of disease activity, and therefore required ranibizumab injections during the study. In these eyes, VA, central retinal thickness (CRT), FS, and TS remained unchanged during follow-up. Peak TS was noted when CRT was 210 MUm; above or below 210 MUm, there was a gradual reduction in TS. CONCLUSION: This study has provided novel information on the relationship between macular sensitivity, CRT, and VA in the maintenance phase of ranibizumab therapy. Patients with stable VA and CRT may still have deteriorating retinal sensitivity. This is usually a late manifestation and may indicate subclinical CNV activity. PMID- 22322999 TI - Cytomegalovirus retinitis successfully treated with ganciclovir implant in a patient with blood ganciclovir resistance and ocular ganciclovir sensitivity. PMID- 22323000 TI - Acquired Brown's syndrome following cosmetic blepharoplasty. PMID- 22323001 TI - Relationship between running loads and soft-tissue injury in elite team sport athletes. AB - Although the potential link between running loads and soft-tissue injury is appealing, the evidence supporting or refuting this relationship in high performance team sport athletes is nonexistent, with all published studies using subjective measures (e.g., ratings of perceived exertion) to quantify training loads. The purpose of this study was to investigate the risk of low-intensity (e.g., walking, jogging, total distances) and high-intensity (e.g., high acceleration and velocity efforts, repeated high-intensity exercise bouts) movement activities on lower body soft-tissue injury in elite team sport athletes. Thirty-four elite rugby league players participated in this study. Global positioning system data and the incidence of lower body soft-tissue injuries were monitored in 117 skill training sessions during the preseason and in-season periods. The frailty model (an extension of the Cox proportional regression model for recurrent events) was applied to calculate the relative risk of injury after controlling for all other training data. The risk of injury was 2.7 (95% confidence interval 1.2-6.5) times higher when very high-velocity running (i.e., sprinting) exceeded 9 m per session. Greater distances covered in mild, moderate, and maximum accelerations and low- and very low-intensity movement velocities were associated with a reduced risk of injury. These results demonstrate that greater amounts of very high-velocity running (i.e., sprinting) are associated with an increased risk of lower body soft-tissue injury, whereas distances covered at low and moderate speeds offer a protective effect against soft-tissue injury. From an injury prevention perspective, these findings provide empirical support for restricting the amount of sprinting performed in preparation for elite team sport competition. However, coaches should also consider the consequences of reducing training loads on the development of physical qualities and playing performance. PMID- 22323002 TI - Prospectively measured thyroid hormones and thyroid peroxidase antibodies in relation to breast cancer risk. AB - Thyroid hormones influence both normal breast cell differentiation and breast cancer cell proliferation and stimulate the angiogenesis of certain cancer forms. Several cross-sectional studies have measured thyroid hormones/autoantibodies in breast cancer ceases vs. controls, but it is difficult to determine the cause effect direction in these studies. Only three prospective studies have reported on the subject so far. The aim of our study was to investigate prediagnostically measured levels of thyroid hormones, thyrotropin (TSH) and thyroid autoantibodies in relation to subsequent risk of breast cancer. The Malmoe Diet and Cancer study examined 17,035 women between 1991 and 1996. Blood samples were collected at baseline and free triiodothyronine (T3), free thyroxin (T4), TSH and thyroid peroxidase autoantibodies (TPO-Ab) levels were measured in 676 cases and 680 controls. Relative risks with 95% confidence intervals were assessed using a logistic regression analysis adjusted for potential confounders. Free T4 levels were positively associated with a high risk of breast cancer, and the OR for women with free T4 levels above vs. below the median was 1.40 (1.10-1.77). This association was most pronounced in overweight women (1.51:1.07-2.12). Women with high levels of TPO-Ab had a lower risk of breast cancer, but only the analysis of TPO-Ab as a continuous variable reached statistical significance. Free T4 was in our study positively associated with a high risk of breast cancer. This association was most pronounced in overweight/obese women. Women with a high level of TPO-Ab had a relatively low risk of breast cancer. PMID- 22323003 TI - Dynamic enhancing vascular pattern of intrahepatic peripheral cholangiocarcinoma on contrast-enhanced ultrasound: the influence of chronic hepatitis and cirrhosis. AB - PURPOSE: To analyse the dynamic enhancing features by real-time contrast-enhanced ultrasound (CEUS) of intrahepatic peripheral cholangiocarcinoma (ICC) in patients with chronic hepatitis and cirrhosis. MATERIALS AND METHODS: CEUS was performed by using contrast pulse sequencing (CPS) imaging with mechanical index of <0.2 after injection of 2.4 mL of contrast agent. CEUS images of histologically confirmed ICC in 54 patents (15 patents with chronic hepatitis B, 16 patents with cirrhosis, and 23 patents with normal underlying liver) were analyzed. RESULTS: Heterogeneous hyperenhancement was more frequently identified in ICC with chronic hepatitis (9 of 15, 60.0%, p = 0.000) and cirrhosis (8 of 16, 50.0%, p = 0.010) than in patients with normal liver (6 of 23, 26.1%) during arterial phase. The majority of ICC in patients with normal liver displayed peripheral hyperenhancement (13 of 23, 56.5%), than in patients with chronic hepatitis (4 of 15, 26.7%, p = 0.000) and cirrhosis (5 of 16, 31.3%, p = 0.001). Intense contrast uptake during the arterial phase (heterogeneous hyperenhancement or global hyperenhancement) followed by washout in venous phases was more frequently displayed in ICC patients with chronic hepatitis (11 of 15, 73.3%, p = 0.000) and in patients with cirrhosis (11 of 16, 68.8%, p = 0.000) than in ICC patients with normal underlying liver (8 of 23, 34.8%). CONCLUSION: The enhancing vascular pattern of ICC on CEUS in patients with chronic hepatitis and cirrhosis is different from that in ICC without underlying liver disease. The enhancing vascular pattern is indistinguishable from HCC on CEUS in most ICC patients with chronic hepatitis or cirrhosis. PMID- 22323004 TI - A review of the literature on event-level substance use and sexual risk behavior among men who have sex with men. AB - In the United States, there continues to be high incidence of HIV infection among men who have sex with men (MSM), who represent 57% of new infections in 2009. While many studies report associations between non-injection substance use and sexual risk behavior among MSM, overall results are mixed. Summarizing these studies is difficult because researchers have used a variety of assessment periods for substance use and sexual behavior. We review the scientific literature on event-level measures, which assess substance use and sexual risk behavior immediately before or during a sexual encounter and provide the most precise link between these two behaviors. From January 2009 through March 2010, we searched four databases: Ovid (MEDLINE and PsycINFO), Web of Knowledge, and Sociofile. Across studies, results varied by substance with little within substance consistency or a lack of research except for two notable exceptions: methamphetamine and binge alcohol use. The findings underscore the importance of providing HIV risk-reduction interventions for substance-using MSM. PMID- 22323005 TI - Depressive symptoms among MSM who engage in bareback sex: does mood matter? AB - Much research has examined the relationship between depressive symptoms and unprotected sex among men who have sex with men (MSM), but little is known about how depression is related to the sexual behavior of men who intentionally engage in unprotected anal intercourse, or bareback sex. In this study, we explored the extent to which depressive symptoms were associated with rates of unprotected sex among barebackers, and whether this relationship was dependent upon HIV serostatus. Using a sample of 120 MSM who engage in intentional condomless sex, we found that for HIV-negative participants, depressive symptoms were associated with the overall frequency of unprotected anal intercourse as well as unprotected anal intercourse with a serodiscordant partner. For HIV-positive participants, depressive symptoms were not associated unprotected intercourse. Additional research is needed to better understand depression among men who bareback and how interventions could be designed to address depression and reduce sexual risk behaviors. PMID- 22323006 TI - Predicting discordance between self-reports of sexual behavior and incident sexually transmitted infections with African American female adolescents: results from a 4-city study. AB - This study examined correlates of the discordance between sexual behavior self reports and Incident Sexually Transmitted Infections. African American adolescent females (N = 964) from four U.S. cities were recruited for an HIV/STI prevention trial. Self-reported sexual behaviors, demographics, and hypothesized psychosocial antecedents of sexual risk behavior were collected at baseline, 6-, 12-, and 18-month follow-up assessments. Urine specimens were collected and tested for three prevalent STIs (chlamydia, gonorrhea, trichomonas) at each assessment. Seventeen percent of participants with a laboratory-confirmed STI reported either lifetime abstinence or recent abstinence from vaginal sex (discordant self-report). Lower STI knowledge, belief that fewer peers were engaging in sex, and belief that more peers will wait until marriage to have sex were associated with discordant reports. Discordance between self-reported abstinence and incident STIs was marked among African American female adolescents. Lack of STI knowledge and sexual behavior peer norms may result in underreporting of sexual behaviors. PMID- 22323007 TI - Murine models and cell lines for the investigation of pheochromocytoma: applications for future therapies? AB - Pheochromocytomas (PCCs) are slow-growing neuroendocrine tumors arising from adrenal chromaffin cells. Tumors arising from extra-adrenal chromaffin cells are called paragangliomas. Metastases can occur up to approximately 60% or even more in specific subgroups of patients. There are still no well-established and clinically accepted "metastatic" markers available to determine whether a primary tumor is or will become malignant. Surgical resection is the most common treatment for non-metastatic PCCs, but no standard treatment/regimen is available for metastatic PCC. To investigate what kind of therapies are suitable for the treatment of metastatic PCC, animal models or cell lines are very useful. Over the last two decades, various mouse and rat models have been created presenting with PCC, which include models presenting tumors that are to a certain degree biochemically and/or molecularly similar to human PCC, and develop metastases. To be able to investigate which chemotherapeutic options could be useful for the treatment of metastatic PCC, cell lines such as mouse pheochromocytoma (MPC) and mouse tumor tissue (MTT) cells have been recently introduced and they both showed metastatic behavior. It appears these MPC and MTT cells are biochemically and molecularly similar to some human PCCs, are easily visualized by different imaging techniques, and respond to different therapies. These studies also indicate that some mouse models and both mouse PCC cell lines are suitable for testing new therapies for metastatic PCC. PMID- 22323008 TI - From transcriptional profiling to tumor biology in pheochromocytoma and paraganglioma. AB - This review summarizes the way in which inherited mutations define global gene expression in pheochromocytoma (PCC) and paraganglioma (PGL), and how the use of gene expression analysis has advanced our understanding of these diseases. The biology of PCC and PGL tumors is diverse and it has become clear that there is no apparent single biology that defines these tumors. However, over the last 20 years, our understanding of the biology of PGL and PCC has been considerably advanced by the discovery of inherited mutations that predispose individuals to developing the disease. More recently, the use of transcriptomics to stratify tumors based on their gene expression profiles has, in particular, played a vital role in delineating novel mutations involved in the pathogenesis of these tumors. In this review, we describe our current understanding of the biology of cluster 1 (pseudohypoxic) tumors and how mutations that result in the pseudohypoxic phenotype that leads to changes in global gene expression. We also review the advances in our understanding of cluster 2 tumors, and in particular, focus on the newly described MAX tumors. PMID- 22323009 TI - Mortality of intra-abdominal desmoid tumors in patients with familial adenomatous polyposis: a single center review of 154 patients. AB - INTRODUCTION: Intra-abdominal desmoid tumors are one of the leading causes of death in patients with familial adenomatous polyposis. Their behavior is unpredictable and their biology is poorly understood, accounting for the lack of a standardized medical and surgical approach. The aim of this study was to evaluate the mortality rate of patients with intra-abdominal desmoid tumors and to identify prognostic factors for the evolution of the disease. MATERIALS AND METHODS: A total of 154 patients with intra-abdominal desmoid tumors were included in the study. Each tumor was staged and each patient was categorized according to the stage of their most advanced tumor. Mortality was analyzed and the univariate risk factors associated with survival were included in a multivariable Cox regression model. A scoring system was derived from the multivariate analysis to refine outcomes within stages. RESULTS: Five-year survival of patients with stage I, II, III, and IV intra-abdominal desmoid tumor were 95%, 100%, 89%, and 76% respectively (P < 0.001). Severe pain/narcotic dependency, tumor size larger than 10 cm, and need for total parenteral nutrition were shown to further define survival within stages. Five-year survival rate of stage IV patient with all of the above-mentioned risk factors was only 53%. CONCLUSIONS: Our study confirmed the validity of the staging system to predict mortality in patients with intra-abdominal desmoid tumors and identified additional risk factors able to better define the risk of death within each stage. Risk stratification is crucial in directing patients with advanced disease and poor prognosis to the most appropriate medical and surgical options. PMID- 22323010 TI - Significant contribution of the portal vein to blood flow through the common bile duct. AB - OBJECTIVE: The aim of this study was to determine the contribution of the hepatic artery, gastroduodenal artery, and portal vein to the microvascular blood flow in the common bile duct (CBD). BACKGROUND: Biliary complications are a common cause of graft loss after liver transplantation. The occurrence is, partly, attributed to hepatic artery thrombosis, which is considered to be the sole provider of blood flow to the bile ducts. However, the contribution of the portal vein and the gastroduodenal artery to the bile ducts is unknown. METHODS: Microvascular blood flow in the CBD was determined in 15 patients who underwent a pancreaticoduodenectomy with a combination of laser Doppler flowmetry and reflectance spectrophotometry. Microvascular blood flow was measured at baseline, during clamping the portal vein, during clamping the hepatic artery, and during clamping both. After transection of the CBD, these 4 measurements were repeated. RESULTS: Compared with baseline measurements, the microvascular blood flow through the CBD decreased to 62% after clamping the portal vein, 51% after clamping the hepatic artery, and 31% after clamping both. After the CBD was transected, these 3 measurements were 60%, 31%, and 20%, respectively. CONCLUSIONS: : Historically, the hepatic artery has been considered mainly responsible for biliary blood flow. We show that after transection of the CBD, mimicking the situation after liver transplantation, the contribution of the portal vein to the microvascular blood flow through the CBD is 40%. This study emphasizes the importance of the portal vein, and disturbances in portal venous blood flow could contribute to the formation of biliary complications after liver transplantation. PMID- 22323011 TI - Thoracoscopic pleurodesis for primary spontaneous pneumothorax with high recurrence risk: a prospective randomized trial. AB - OBJECTIVE: To compare the efficacy and safety between apical pleurectomy and pleural abrasion with minocycline in primary spontaneous pneumothorax (PSP) with high recurrence risk. BACKGROUND: The optimal thoracoscopic pleurodesis procedure for PSP with high recurrence risk remains controversial. METHODS: Between January 2006 and May 2009, a total of 369 patients with spontaneous pneumothorax were treated by video-assisted thoracoscopic surgery. After stapled bullectomy, 160 patients with no identifiable bleb or multiple blebs (>=3) were randomly chosen to undergo apical pleurectomy (pleurectomy group, 80 patients) or pleural abrasion with minocycline (abrasion/minocycline group, 80 patients). RESULTS: Patients in the pleurectomy group had a longer operation duration (mean, 81.4 minutes vs 55.8 minutes, P < 0.001), a greater amount of operation bleeding (mean, 29.4 mL vs 13.2 mL, P = 0.025), and a greater amount of postoperative chest drainage (mean, 287.4 mL vs 195.8 mL, P = 0.040). Patients in the abrasion/minocycline group had a higher intensity of chest pain and required more frequent meperidine injections. Hemothorax occurred in 3 pleurectomy patients (3.8%). The short-term results showed that the 2 groups had comparable durations of postoperative chest drainage, durations of postoperative hospital stay, and complication rates. After a mean follow-up of 26.1 months, recurrent ipsilateral pneumothorax occurred in 3 patients (3.8%) in the pleurectomy group and 3 patients (3.8%) in the abrasion/minocycline group. Postoperative long-term residual chest pain and pulmonary function were comparable in both groups. CONCLUSIONS: : Pleural abrasion with minocycline pleurodesis is as effective as apical pleurectomy and either technique is appropriate for treating PSP patients with high recurrence risk. This trial was registered at http://www.clinicaltrials.gov (ID: NCT00270751). PMID- 22323012 TI - The influence of body mass index on life quality and clinical improvement after total hip arthroplasty. AB - BACKGROUND: The effect of body mass index (BMI) on the outcome of total hip arthroplasty (THA) remains controversial. The purpose of this study was to examine whether revision rate and postoperative outcomes following THA were influenced by BMI. MATERIALS AND METHODS: We retrospectively evaluated 714 patients (751 hips) who underwent primary THA in our department between March 1991 and April 2006. They were followed prospectively for 5-20 years with 24 deaths (24 hips) and 33 losses (34 hips). Patients were separated into three groups based on BMI: underweight, normal and obese groups. A survival analysis was performed using revision as the endpoint, and a case-matched study that was matched for age, gender, and laterality was designed; outcomes were assessed with the Harris Hip score, 36-item short-form health survey, complication rate and radiological examination. RESULTS: The preoperative scores were lower for the obese group, and the postoperative scores were higher for the normal group. Patients in the obese group obtained the greatest overall improvement in clinical scores from admission to the last follow-up. We found a significantly higher complication rate in the obese group and underweight group. It appears that being underweight was associated with an increased dislocation rate, and obese patients were more likely to have osteolysis, deep vein embolism, and pulmonary thrombosis. The log rank test for survival showed no significant differences among the three groups. CONCLUSIONS: Abnormal BMI does not prevent functional rehabilitation after THA; however, patients with abnormal BMI have to face higher complication rates and poorer clinical outcomes following this operation. PMID- 22323013 TI - Alterations in stress distribution patterns through the forearm joint surface of the elbow in baseball players assessed using computed tomography osteoabsorptiometry. AB - BACKGROUND: The distribution of subchondral bone density well reflects long-term resultant stress acting on an articular surface in living joints. Consequently, a measurement of the distribution pattern can determine the stress distribution across the elbow joint surface under long-term loading conditions of baseball pitching. Our purpose was to elucidate the characteristic alterations in the distribution pattern of subchondral bone density across the forearm bones of the elbow with pitching activities. The hypothesis is that pitching activities would change the stress distribution in living subjects. METHODS: The analysis was performed using computed tomography (CT) images obtained from the dominant elbow of ten nonthrowing athletes (control group), ten college baseball fielders (fielder group), and ten college baseball pitchers (pitcher group). The distribution pattern of subchondral bone density through the articular surface of the proximal radius and ulna bones was assessed using CT osteoabsorptiometry. RESULTS: The maximum density area was located in the posterior part of the trochlea notch in all study participants. This maximum density area was significantly increased in the baseball groups compared with that in the control group. The pitcher group also showed a significant distribution of the maximum density area in the anterior part of the radial head. CONCLUSION: Our analysis indicates that pitching activities increase actual stress on the articular surface not only in the posterior part of the trochlea notch but also in the anterior part of the radial head. The stress across the elbow may be expanded from the ulnohumeral to the radiohumeral joint by repetitive pitching activities in living subjects. PMID- 22323014 TI - On the structure of the Au18(SR)14 cluster. AB - First principles calculations are used for a systematic search of the lowest energy (most-stable) structure of the recently synthesized Au(18)(SR)(14) cluster. A comparison of the calculated optical absorption and electronic circular dichroism spectra, which are highly sensitive to the cluster structure and chirality, with the experimental spectra of the glutathione-protected gold cluster, Au(18)(SG)(14), is used to discriminate between low-energy isomers of the Au(18)(SR)(14) (R = CH(3)) cluster. From the good agreement between calculated and measured spectra, it is predicted that the structure of the Au(18)(SR)(14) cluster consists of a prolate Au(8) core covered with two dimer (SR-Au-SR-Au-SR) and two trimer (SR-Au-SR-Au-SR-Au-SR) motifs. These results provide additional evidence on the existence of longer trimer motifs as protecting units of small thiolated gold clusters. PMID- 22323015 TI - [Pearls and pitfalls on diagnosing infections in the elderly]. PMID- 22323016 TI - [Rationale use of oral antibiotics for elderly patients]. PMID- 22323017 TI - [Antibiotics in the elderly: injection drugs]. PMID- 22323018 TI - [Prevention of infectious diseases in older adults]. PMID- 22323019 TI - [Cerebrovascular diseases in the elderly on a geriatric viewpoint]. PMID- 22323020 TI - [Urinary incontinence (storage problem) in the elderly]. PMID- 22323021 TI - [Present status and controversies on ambulance transport of elderly patients from viewpoint of Emergency Medical Center]. PMID- 22323022 TI - [Respiratory diseases in the elderly]. PMID- 22323023 TI - [Major medical issues in the disastered elderly by M-9 earthquake on March 11, 2011]. PMID- 22323024 TI - [What has been brought to residents and communities by the nuclear power plant accident? Special and serious disaster relief procedure modification after the 2011 Tohoku earthquake and tsunami in Fukushima]. AB - After the catastrophic 2011 Tohoku earthquake and tsunami which struck cities and towns on the Japanese Pacific coast, Fukushima has been the focus of special and serious disaster relief procedures modification regarding nuclear power plant accidents. To date, the Japanese government has repeatedly issued evacuation orders to more than 100,000 residents. Huge numbers of refugees are still uncertain if they can return home and re-cultivate their farm land. Ambiguous public announcements concerning the radiation risks seem to have aggravated feelings of insecurity, fear and the desire to escape, both at home and abroad. This disaster has seriously undermined trust internationally and locally in Fukushima. Harmful rumors added further difficulties. In response to this disaster, local government, medical institutions, care facilities, police, emergency services and the self-defense forces continue to put their utmost effort into reconstruction. This seismic disaster has reminded us that supplies of water, electricity, gas, gasoline and telephone/communication facilities are essential prerequisites for reconstruction and daily life. Disaster and radiation medical association teams actively participated in the rescue efforts, and a number of organized medical teams cared for about 15,000 refugees in 100 shelters. We also visited home-bound patients, who were unable to evacuate from the 20-30 km inner evacuation area. In this relief role, we need to consider the following; (1) professionals, both healthcare and nuclear engineers, must always be prepared for unexpected circumstances, (2) the daily organic cooperation of individuals and units is closely linked to readiness against sudden risks, and (3) appropriate accountability is essential to assuage the fears of residents and refugees. A sincere learning process may benefit those innocent refugees who may be forced to abandon their homes permanently. PMID- 22323025 TI - [A step to reduce disaster-related illnesses based on various stress: what should we learn from the 2011 off the Pacific Coast of Tohoku Earthquake? -Report from Japan Geriatric Society-]. PMID- 22323026 TI - [Management of infectious diseases and infection control in elderly evacuees in shelters]. PMID- 22323027 TI - [Nutrition and related gastroenterology disorders among elderly evacuees]. PMID- 22323028 TI - [Mental support for elderly people]. PMID- 22323029 TI - [End-of-life care in a special elderly nursing home characteristics of patients who died in nursing home facilities and current status of end-of-life decision making]. AB - AIM: We investigated the characteristics of people who died in a special elderly nursing home and the current status of end-of-life decision-making. METHODS: Subjects comprised 168 residents who were discharged from a special elderly nurshing home in Yokohama between April 1998 and June 2008. A total of 3 patients were excluded from this study due to insufficient inclusion criteria. We collected and retrospectively examined the basic descriptive information regarding the terminal phase of care from medical records, death certificates, and the notes of nurses, caregivers and counseling staff. RESULT: Of a total of 165 subjects comprising 38 men (23%) and 127 women (77%), 30 (18%) died in a nursing home facility (facility mortality group), 101 (61%) died in hospitals (hospital mortality group) and 34 (21%) were discharged from special elderly nursing homes for transfer to long-term hospitalization (hospitalization group). To clarify the factors which led to death within the facilities, we analyzed: 1) age at discharge, 2) sex, 3) residency period, 4) number of hospitalizations, 5) length of hospital stay, 6) number of children, 7) number of conferences regarding end-of-life care in 2 groups: the facility mortality group and all others as the second group, as explanatory variables on multiple discriminant analysis. This revealed a higher number of conferences, a higher age at discharge, and a smaller number of hospitalizations in the facility mortality group. Only 12 (7%) people were able to convey by themselves how they wanted to spend the remainder of their lives, and 61 (37%) people conveyed this information via family members. However, 100 (61%) people were unable to confirm it by either self-report or family members. CONCLUSION: The people who died in special elderly nursing homes had a higher age, fewer hospitalizations, and had been involved in more conferences regarding terminal care. However, it was very hard to confirm individual intentions regarding terminal care periods. Further studies will be necessary to determine what kind of terminal care is needed in special elderly nursing homes when it is difficult to confirm individual or family intention regarding the terminal period. PMID- 22323030 TI - [Association of the physical activity of community-dwelling older adults with transportation modes, depression and social networks]. AB - AIM: The purpose of this study was to cross-sectionally examine the relationships among leisure, household and occupational physical activity with the frequency of going out by various transportation modes, depression and social networks in older adults. METHODS: We randomly selected a total of 2,100 community-dwelling adults aged 65 to 85 years of age from the Basic Resident Register. Of these, 340 people were the subjects of this study. The scales of measurement used were the Physical Activity Scale for the Elderly, the Lubben Social Network Scale (LSNS) and the Geriatric Depression Scale (GDS). RESULTS: In a regression model, leisure time physical activity significantly correlated with frequency of going out by bicycle (beta=0.17) and LSNS score (beta=0.17). Household physical activity and occupational physical activity were significantly correlated with LSNS score (beta=0.21) and frequency of going out by motor vehicle (beta=0.25), respectively. For total physical activity, in the 3 above-mentioned activities a significant correlation was observed among frequency of going out by bicycle (beta=0.10), by motor vehicle (beta=0.23), GDS score (beta=-0.16) and LSNS score (beta=0.23). CONCLUSION: These results indicate that the frequency of going out by bicycle and by motor vehicle were significant factors to predict leisure and occupational physical activity. Furthermore, social networks appear to be important determiners in leisure and household physical activity in community dwelling older adults. PMID- 22323031 TI - [Confirmation of intention by signature regarding terminal care treatment in elderly people]. AB - AIM: In Japan, it is rare for patients to confirm their intentions regarding terminal care treatment in hospital by signature. To maintain respect for the autonomy of elderly patients, we encouraged confirmation by signature regarding terminal care treatment in elderly patients, after repeated discussions. The purpose of this study was to clarify the status of confirmation of intention by signature. METHOD: The subjects were 98 patients who signed documents signaling their intention regarding terminal care (signature group), and 165 patients who did not sign such documents (non-signature group), all of whom died in our hospital between April 2009 and March 2010. We surveyed and examined their backgrounds and treatment experiences based on the clinical records. Furthermore, we gave a questionnaire survey to these patients. A total of 31 (35.2%) patients from the signature group and 58 (35.2%) patients from the non-signature group responded. RESULTS: In the signature group 32 (32.7%) patients judged to be in a terminal state were discharged alive. Those in the signature group had a significantly higher age, higher ratio of dementia, lower activity level in their daily life and were hospitalized with respiratory illnesses. In addition, the frequency of the informed consent discussions was greater than that of the non signature group. A total of 90% of the signature group was able to accept the confirmation of their intention regarding terminal care by signature. In both groups, the doctors' explanations were understood, and the patients' wishes were successfully conveyed. CONCLUSION: In Japan, confirmation of intention regarding terminal care by signature can be effective and useful as one of the methods to determine intention regarding terminal care treatment in elderly patients. PMID- 22323032 TI - [Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is frequently detected as a pathogen of urinary tract infection in nursing home residents]. AB - AIM: To assess the prevalence of the fecal carriage of extended-spectrum beta lactamase (ESBL)-producing Escherichia coli among nursing home residents and to demonstrate the relationship between fecal carriage and urinary tract infections (UTIs) in elderly patients. METHODS: Data were collected for 12 months on aerobic bacteria obtained from the urine of elderly patients with UTI. Feces were analyzed for the bla(CTX-M) gene at the Department of Bioinformatics, Osaka University Graduate School of Medicine. RESULTS: Among 56 strains of aerobic bacteria obtained from 40 patients with UTIs, there were 24 strains of Escherichia coli, 14 (58.3%) of which were ESBL-producing. All of these ESBL strains were also resistant to levofloxacin (LVFX). Fecal ESBL-carriage was detected in 21.5% of the residents, with similar ratios in men and women. Statistical analysis of the backgrounds of residents showed that the carriage rate was markedly high in those elderly patients who came from hospitals after the treatment of infectious/purulent diseases. Among the 145 residents, whose feces were analyzed for ESBL, UTIs developed in 10 patients, only 1 of whom was a man; urinary examination did not detect ESBL-producing Escherichia coli as a pathogen in this patient. In 9 female patients, ESBL-producing Escherichia coli was isolated from the urine of 8 women. While the combination of fosfomycin and minomycin was useful in the treatment of the UTIs in these cases, it did not completely remove the ESBL-producing bacteria from feces. CONCLUSIONS: Fecal carriage of ESBL-producing Escherichia coli is prevalent in our facilities and is related to a high incidence of UTIs in elderly women, presenting treatment challenges. PMID- 22323033 TI - [Decision trees on gait independence in patients with femoral neck fracture]. AB - PURPOSE: The purpose of this study was to develop a decision-making process to assess the conditions for predicting gait independence in patients with femoral neck fracture. METHODS: A total of 108 patients were divided into 2 groups on the basis of their walking abilities at discharge for an unrelated illness; an independent (n=55) and dependent group (n=53). Details regarding age, sex, length of hospital therapy, operative procedures, classification of fracture, past history of stroke and fracture were collected from medical records. Body mass index (BMI), knee extension power, maximum walking speed, functional reach test (FRT) and the mini-mental state examination (MMSE) were measured to evaluate motor ability and cognitive status at discharge. Student's t-test and the chi squared test were used to test for statistical differences between the 2 groups. On multivariate analysis, classification and regression trees (CART) was used to determine the predictive value of those measures that differed significantly between the 2 groups. RESULTS: On bivariable analysis, significant differences were found in nearly all variables, except for BMI and length of hospital therapy. As a result of this analysis, the decision tree, which consists of knee extension power, FRT, MMSE and a past history of stroke, was created. CART analyses showed that when knee extension power was >0.34 kgf/kg, the MMSE score was >13.5; with no past history of stroke, the rate of independent walking at discharge was 93.8%. In contrast, when knee extension power was <=0.33 kgf/kg, FRT was <=25.5 cm, the MMSE score was <=13.5, and the rate of dependent walking at discharge was 100%. CONCLUSIONS: Our findings indicate that the decision tree can be helpful in predicting gait independence in patients with femoral neck fracture. PMID- 22323034 TI - [The validity of the "Kihon Check-list" as an index of frailty and its biomarkers and inflammatory markers in elderly people]. AB - AIM: The present study was designed to assess the validity of the "Kihon ("basic") Check-list (KCL)" as a frailty index, and to investigate its biomarkers in an elderly population. METHODS: We enrolled 420 elderly persons aged 65 years and over in comprehensive geriatric assessments in 2007 and 2008. We examined the temporal relationship between the Fried frailty criteria (external criteria) and KCL items 1-20 to evaluate concurrent validity. In 2008, 665 elderly people aged 65 years and over who participated in the comprehensive geriatric assessment in 2008 were assessed based on their frailty and non-frailty using the KCL. We compared biomarkers, including TNF-alpha, IL-6, CRP and beta(2)-microglobulin (beta(2)-MG) between frail and non-frail groups. RESULTS: The KCL items 1-20 showed good concurrent validity against the Fried criteria in terms of frailty. When using a cut-off point of 5/6, the KCL items 1-20 showed a sensitivity of 60.0% and a specificity of 86.4% for the Fried frailty criteria. Overall, 34 males (12.3%) and 74 females (19.0%) were defined as frail. Among varying biomarkers, IL-6 (odds ratio [OR] of highest tertile vs. lowest tertile, 2.05; 95% confidence interval [CI]: 1.15-3.64), grip strength (OR: 0.19; 95% CI: 0.07 0.46) and walking speed (OR: 0.23; 95% CI: 0.12-0.45) were significantly associated with risks of frailty. The highest tertile of IL-6 and beta(2)-MG combined highly increased the risk of frailty (OR: 5.61; 95% CI: 2.34-13.11) compared with those in the lowest tertile of the 2 markers combined. CONCLUSIONS: The KCL items 1-20 can be used as a frailty index for Japanese elderly population. IL-6 and beta(2)-MG are potential candidates for biomarkers of frailty. PMID- 22323035 TI - [A case of severe hypokalemia caused by a Chinese herbal remedy (Yokukansan) in an 81-year-old woman with dementia]. AB - An 81-year-old woman had been visiting 2 hospitals for hypertension and dementia, prior to admission to our emergency room for nausea, hypertension, severe hypokalemia (K 1.29 mEq/l) and abnormal electrocardiography findings. She had been taking a Chinese herbal remedy (Yokukansan, 7.5 g/day) for the behavioral and psychological symptoms of dementia (BPSD) for 6 months before admission. On admission, she presented with metabolic alkalosis with hypokalemia, a high urinary excretion of potassium, low plasma rennin activity and hypoaldosteronism. We diagnosed pseudoaldosteronism caused by the Chinese herbal remedy Yokukansan (which includes licorice). Discontinuation of Yokukansan and the administration of potassium supplements normalized her serum potassium level within 2 weeks. However, we could not successfully control her BPSD by drugs such as tiapride hydrochloride or risperidone. BPSD is a serious problem in an aging society, with the ever-increasing incidence of dementia. The use of Yokukansan has recently been receiving attention as a new treatment modality for BPSD. Because this agent has relatively few adverse effects compared with typical antipsychotic agents, the use of Yokukansan is continuing to increase sharply. Pseudoaldosteronism, if caused by Yokukansan, may cause death by severe hypokalemia, but the early identification of hypokalemia is sometimes difficult because drug-induced hypokalemia is not dose-dependent. We think it is important to create awareness of the possible adverse effects of Yokukansan, such as hypertension and electrolyte abnormalities to make the most of this commonly used drug for the treatment of BPSD among dementia patients. PMID- 22323036 TI - [Use of honorifics in all situations by a patient with semantic dementia]. AB - We report the case of a 72-year-old man who had been given a diagnosis of semantic dementia (SD) at 64 years of age, and who began to use honorifics in all situations during the later clinical course. His initial clinical features were problems in word comprehension and naming, and some behavioural changes, including clockwatching and aberrant eating behaviours. The most prominent feature in this case was the use of honorifics in all situations, while other aspects of his language ability deteriorated. He even used honorifics with members of his family, including young grandchildren. Although it is difficult to explain the reason why the patient used honorifics in all situations, we considered 2 possibilities. The first is that although he remains able to use honorifics, he is unable to distinguish when the use of honorifics is not required. The second is that a change in emotional state, such as the "taming effect" or "placidity" that has been suggested to accompany frontotemporal lobar degeneration, might have affected his use of honorifics. The regular schedule of daycare services provides him with emotional stability because he does not have to constantly be aware of the time. Since no standard treatment has been established for SD, our experience with this case might be beneficial in caring for patients with SD. PMID- 22323037 TI - [Two cases of fulminant type 1 diabetes mellitus]. AB - We report 2 elderly patients with fulminant type 1 diabetes mellitus. Case 1: A 61-year-old-man was admitted because of hyperglycemia (blood glucose level, 1,071 mg/dl) and metabolic acidosis. His hemoglobin A1c level was almost normal (5.8%), glutamic acid decarboxylase (GAD) antibody was not detected, and a low level of C peptide (CPR) was excreted in his urine. We diagnosed his condition as diabetic ketoacidosis, and administered intensive insulin therapy. Case 2: A 77-year-old man was admitted because of hyperglycemia (blood glucose level, 925 mg/dl). His hemoglobin A1c level was slightly high (5.9%), GAD antibody was not detected, and low levels of CPR were excreted in his urine. He showed no signs of metabolic acidosis, but showed metabolic ketosis. The findings of these cases were consistent with those of fulminant type 1 diabetes mellitus. Thus, it is necessary to consider the possibility of this disease in elderly people. PMID- 22323038 TI - [Resident status is related depression mood in elderly inpatients]. PMID- 22323039 TI - [Education tool for quality postmortem care for elderly]. PMID- 22323040 TI - The health-related quality of life burden of co-morbid cardiovascular disease and major depressive disorder in Australia: findings from a population-based, cross sectional study. AB - PURPOSE: Health-related quality of life (HRQOL) can be significantly impaired by the presence of chronic conditions such as cardiovascular disease (CVD) and major depressive disorder (MDD). The aim of this paper was to (1) identify differences in HRQOL between individuals with CVD, MDD, or both, compared to a healthy reference group, (2) establish whether the influence of co-morbid MDD and CVD on HRQOL is additive or synergistic and (3) determine the way in which depression severity interacts with CVD to influence overall HRQOL. METHODS: Population-based data from the 2007 Australian National Survey of Mental Health and Well-being (NSMHWB) (n = 8841) were used to compare HRQOL of individuals with MDD and CVD, MDD but not CVD, CVD but not MDD, with a healthy reference group. HRQOL was measured using the Assessment of Quality of Life (AQOL). MDD was identified using the Composite International Diagnostic Interview (CIDI 3.0). RESULTS: Of all four groups, individuals with co-morbid CVD and depression reported the greatest deficits in AQOL utility scores (Coef: -0.32, 95% CI: -0.40, -0.23), after adjusting for covariates. Those with MDD only (Coef: -0.27, 95% CI: -0.30, -0.24) and CVD only (Coef: -0.08, 95% CI: -0.11, -0.05) also reported reduced AQOL utility scores. Second, the influence of MDD and CVD on HRQOL was shown to be additive, rather than synergistic. Third, a significant dose-response relationship was observed between depression severity and HRQOL. However, CVD and depression severity appeared to act independently of each other in impacting HRQOL. CONCLUSIONS: HRQOL is greatly impaired in individuals with co-morbid MDD and CVD; these conditions appear to influence HRQOL in an additive fashion. HRQOL alters with depression severity, therefore treating depression and improving HRQOL is of clinical importance. PMID- 22323041 TI - Cognitive-behavioral therapy for insomnia co-morbid with hearing impairment: a randomized controlled trial. AB - The purpose of the current study was to examine the effects of cognitive behavior therapy (CBT-I) for insomnia on patients with insomnia co-morbid with hearing impairment. A randomized controlled design was used with a 3-month follow-up. Thirty-two patients with insomnia co-morbid with hearing impairment were randomized to either CBT-I or a waitlist condition (WLC). The primary outcome was insomnia severity. Secondary outcomes were sleep diary parameters, dysfunction, anxiety, and depression. Compared to WLC, CBT-I resulted in lower insomnia severity at post-treatment and at follow-up (d = 1.18-1.56). Relative to WLC, CBT I also led, at both assessment points, to reduced total wake time (d = 1.39) and increased sleep restoration (d = 1.03-1.07) and sleep quality (d = 0.91-1.16). Both groups increased their total sleep time, but no significant group difference emerged. Compared to WLC, CBT-I resulted in higher function (d = 0.81-0.96) and lower anxiety (d = 1.29-1.30) at both assessment points. Neither CBT-I nor WLC led to improvement on depression. Based on the Insomnia Severity Index, more CBT I (53-77%) than WLC participants (0-7%) were treatment responders. Also, more CBT I (24%) than WLC participants (0%) remitted. In patients with insomnia co-morbid with hearing impairment, CBT-I was effective in decreasing insomnia severity, subjective sleep parameters, dysfunction, and anxiety. These findings are in line with previous results on the effects of CBT-I in other medical conditions. PMID- 22323042 TI - Defective activities, but not secretions, resulting from gene point mutations of human mannan-binding lectin. AB - Human mannan-binding lectin (MBL) plays a pivotal role in innate immunity. Substantial literature supports the belief that three point mutations, CGT52TGT, GGC54GAC and GGA57GAA, in the collagen-like region (CLR) of the human MBL gene, are associated with increased susceptibility to infection, autoimmunity and carcinogenesis. To investigate the mechanisms of MBL deficiency, human wild-type and three variant MBL genes were expressed in COS-7 and Chinese hamster ovary (CHO) cells. Results showed that no apparent differences were found among the levels of gene transcription and protein secretion of four forms of MBL. However, the degree of oligomerization of variant forms of MBL was found to be much lower than that of recombinant human wild-type MBL. The ability of variant MBL proteins to bind mannan was much weaker than that of the wild-type MBL protein, and the MBL variants failed to effectively activate the complement lectin pathway. These data suggested that a lower order oligomer, but not decreased plasma levels of MBL, may be the main result of MBL gene mutations and may be associated with immunodeficiency. PMID- 22323043 TI - CDC4/FBXW7 and the 'just enough' model of tumourigenesis. AB - There is good evidence to show that cancer-causing mutations are not always simple gain- and loss-of-function changes. One example is the APC gene, where the combination of mutations produces a 'just-right' level of Wnt signalling. A recent article by Berger and colleagues posited a 'continuum model' in which increasing or decreasing gene expression of function was linearly associated with tumourigenesis. Berger also proposed an 'obligate haploinsufficiency' or 'fail safe' model, whereby heterozygous mutations produce sufficient derangement for tumourigenesis, yet homozygous mutations are cell-lethal or senescence-causing. One gene highlighted by Berger and colleagues as an example of a gene following a 'continuum' or 'fail-safe' model was FBXW7/CDC4, a gene mutated in several different types of malignancy. We have analysed the COSMIC FBXW7 data. FBXW7 does not obviously follow a 'continuum' or 'fail-safe' model and the most common mutant genotypes are mono-allelic missense changes that affect critical arginine residues involved in interactions with substrates. There is no strong selection for complete loss of FBXW7 protein function, but bi-allelic inactivating mutations do occur. For FBXW7, we suggest a variant of 'just right' which we call 'just enough'. For FBXW7 mutations that occur away from the propellor tips, the heterozygote may have some effect on tumourigenesis, but there is selective pressure for a 'second hit'. For propellor tip mutations, by contrast, there is weak pressure for a 'second hit' because they usually provide sufficient functional derangement on their own. PMID- 22323044 TI - Spatial distribution and temporal trend in concentration of carbofuran, diazinon and chlorpyrifos ethyl residues in sediment and water in Lake Naivasha, Kenya. AB - Chlorpyrifos ethyl was found to be widely distributed in water and sediment in Lake Naivasha. Higher levels were reported in sediment (11.2-30.0 ng g(-1) dry weight (dw) in wet season than in dry season (4.7-17.4 ng g(-1) dw). The mean concentration of chlorpyrifos ethyl in water in wet season ranged between 8.8 and 26.6 MUg L(-1) and decreased to between below detection limit to 14.0 MUg L(-1) in dry season. On average, higher concentrations of chlorpyrifos ethyl were observed in sediment than water samples. Statistical analysis revealed a significant difference in concentration between the seasons, and a significant interaction between seasons and mean concentrations at p <= 0.05. However, levels of diazinon and carbofuran were below the detection limit in all the samples analyzed. Notably, levels of chlorpyrifos ethyl were higher than the maximum allowable limits (0.1 MUg L(-1)) recommended by European Union for drinking water and general water quality criterion for protection of freshwater water organisms (0.083 MUg L(-1)). PMID- 22323045 TI - Potential health risk of total arsenic from consumption of farm rice (Oryza sativa) from the southern Caspian Sea littoral and from imported rice in Iran. AB - In this study, Arsenic (As) was measured in several varieties of imported and local cultivated rice. Soil samples collected from rice farms situated in south Caspian Sea (Iran) were also studied. The mean concentration of As in imported rice, local farmed rice and soil, were determined as 0.28, 0.39 and 3.80 MUg g( 1) dry weight, respectively. Estimated daily intake of As through human consumption of imported and local produced rice was 0.77 and 1.074 MUg day(-1) kg(-1) B.W., respectively. These values are much lower than the tolerable daily intakes estimated by JECFA. The As concentration in the soil (3.80 MUg g(-1) dry) was below acceptable limit for agricultural soil of 20.0 mg kg(-1) as recommended by the European Community (EC). No correlation between the As concentrations in rice and soil samples was found (p > 0.05). PMID- 22323046 TI - Mercury levels in sediments and mangrove oysters, Crassostrea rizophorae, from the north coast of Villa Clara, Cuba. AB - Total mercury levels were quantified in sediments and oyster tissues (Crassostrea rizophorae) from the Sagua la Grande River estuary and offshore mangrove keys 19 km downstream of a chlor-alkali plant (CAP) in Villa Clara, Cuba. Relatively elevated total mercury levels were found in sediments from the estuary itself, ranging from 0.507 to 1.81 MUg g(-1) dry weight. However, levels were lower in sediments from the keys farther from the estuary. Oyster mercury levels were always acceptable for human consumption, although levels significantly correlated in sediments and oysters across sampling sites (p < 0.05), which suggests that mercury from the CAP is impacting coastal water quality conditions. PMID- 22323047 TI - Organochlorine pesticide residues in blood samples of agriculture and sheep wool workers in Bangalore (rural), India. AB - To describe exposure level of organochlorine pesticides (OCP) among workers occupationally engaged in agriculture and sheep wool associated jobs, the present study was carried out in rural neighborhood of Bangalore city, India. Thirty participants were interviewed and obtained informed consent before blood sample collection. The maximum concentrations of OCP were detected in blood samples of agriculture workers than sheep wool workers. Among the metabolites of HCH and DDT, lindane (gamma-HCH) and p,p'-DDE were the most contributed to the total OCP. There were no differences in pesticide residues found between sex and work groups. It was observed that about 30% of samples exceeded the tolerance limits of 10 MUg/L prescribed for HCH under the prevention of food adulteration act. Therefore, the present study recommends continuous monitoring with larger sample size. PMID- 22323048 TI - Contamination of cows milk by heavy metal in Egypt. AB - The present investigation was carried out to assess the residues levels of five metals (Cadmium, Copper, Lead, Iron and Zinc) in cow milk collected from different sites in El-Qaliubiya governorate, Egypt. A total of 100 cow milk samples were collected from twenty cows in each location sites during the morning milking in the period from March to April, 2011. The highest average concentration are those of iron (16.38 MUg/g) followed by zinc (10.75 MUg/g) and lead (4.404 MUg/g), while the lowest mean concentration are 2.836 and 0.288 MUg/g for copper and cadmium, respectively. The results showed that most of the milk samples from the different sites containing all the studied metals with concentration higher than those recommended for milk by international dairy federation standard and Codex. PMID- 22323049 TI - Effect of moisture and organic manure on persistence of flubendiamide in soil. AB - Persistence of flubendiamide in soil as affected by moisture and organic manure was studied. The present study reports persistence of flubendiamide [N (2)-{1,1 dimethyl-2-{methylsulfonyl) ethyl}-3-iodo-N (1)-{2-methyl-4-{1,2,2,2-tetrafluoro 1 (trifluoromethyl) ethyl} phenyl}-1,2-benzene dicarboxamide] in a sandy loam soil. Dissipation of the pesticide followed mono-phasic first order kinetics. The persistence of flubendiamide was more in dry soil followed by field capacity and submerged condition with half life values of 150.5-158.4 days for submerged soil, 177.0-181.1 days for field capacity soil and 206.6-215.0 days for dry soil. It was found that there is slight effect of fortification level on dissipation of flubendiamide in soil. In all the cases i.e. dry, field capacity and submerged condition dissipation was slightly slower at 10 MUg g(-1) level. Amendment of organic manure (2.5%) to the soil enhanced the degradation of the insecticide, and the half-life values in field capacity and submerged soils were 155.1 and 130.8 days, respectively. PMID- 22323050 TI - Degradation dynamics of flubendiamide in different types of soils. AB - Residual dynamics of flubendiamide in three different types of soils were investigated under laboratory condition. Flubendiamide was applied at 5 and 10 MUg g(-1) for each soil and samples drawn periodically were analyzed on HPLC. The results showed that the degradation of flubendiamide in soils were followed first order kinetics and its average half-lives in three kinds of soils were ranged from 37.62 to 60.21 days. The persistence of flubendiamide in soils significantly increased in the order of coastal soil > red and lateritic soil > new alluvial. PMID- 22323051 TI - Soil contamination of metals in the three industrial estates, Arak, Iran. AB - The aim of this study was to determine the concentrations and degree of metals contamination (Chromium, Cadmium, Nickel and Lead) and Arsenic in the soils of the three Industrial Estates in Arak city, Iran. The average concentrations of Arsenic, Chromium, Cadmium, Nickel and Lead were 5.06, 1.26, 37.13, 67.84 and 60.22 mg kg(-1), respectively. Pearson correlation indicated that Arsenic, Cadmium and Lead were mainly derived from anthropogenic inputs, and Chromium and Nickel were controlled by natural source, whereas Nickel appeared to be affected by both anthropogenic and natural sources. The geo-accumulation Index (Igeo) calculated in three industrial estates gave values indicating unpolluted to strongly polluted. PMID- 22323052 TI - Efficacy of anti-insulin-like growth factor I receptor monoclonal antibody cixutumumab in mesothelioma is highly correlated with insulin growth factor-I receptor sites/cell. AB - Insulin growth factor-I receptor (IGF-IR) is expressed in mesothelioma and therefore an attractive target for therapy. The antitumor activity of cixutumumab, a humanized monoclonal antibody to IGF-IR, in mesothelioma and relationship to IGF-IR expression was investigated using eight early passage tumor cells obtained from patients, nine established cell lines and an in vivo human mesothelioma tumor xenograft model. Although IGF-IR expression at the mRNA and protein level was present in all mesothelioma cells, using a quantitative ELISA immunoassay, there was considerable variability of IGF-IR expression ranging from 1 to 14 ng/mg of lysate. Using flow cytometry, the number of IGF-IR surface receptors varied from ~ 2,000 to 50,000 sites/cell. Cells expressing >10,000 sites/cell had greater than 10% growth inhibition when treated with cixutumumab (100 MUg/ml). Cixutumumab also induced antibody-dependent cell mediated toxicity (>10% specific lysis) in cell lines, which had >20,000 IGF-IR sites/cell. Treatment with cixutumumab decreased phosphorylation of IGF-IR, Akt and Erk in cell lines, H226 and H28 having 24,000 and 51,000 IGF-IR sites/cell, respectively, but not in the cell line H2052 with 3,000 IGF-IR sites/cell. In vivo, cixutumumab treatment delayed growth of H226 mesothelioma tumor xenografts in mice and improved the overall survival of these mice compared to mice treated with saline (p < 0.004). Our results demonstrate that the antitumor efficacy of cixutumumab including inhibition of IGF-IR downstream signaling is highly correlated with IGF-IR sites/cell. A phase II clinical trial of cixutumumab is currently ongoing for the treatment of patients with mesothelioma. PMID- 22323053 TI - Determination of aflatoxins in medicinal herbs by high-performance liquid chromatography-tandem mass spectrometry. AB - INTRODUCTION: We report a rapid and accurate method to determine the natural occurrence of aflatoxins (AFs) B1, B2, G1 and G2 in medicinal herbs and the analysis of 174 commercial samples by this method. OBJECTIVE: The aim of the present work is to examine the occurrence of the aflatoxins B1, B2, G1 and G2 in common medicinal herbs. METHODOLOGY: The AFs were extracted, purified by immunoaffinity column and analysed by high-performance liquid chromatography tandem quadrupole mass spectrometry with electrospray ionisation (HPLC-MS/MS). RESULTS: The AFs can be separated within 6 min using an Agilent XDB C18-column. The target analyte AFB1 could be detected at 0.14 ug/kg. A good linear relationship was found for AFG1 and AFB1 in 1-100 pg and AFG2 and AFB2 in 0.8-30 pg (r > 0.9995). The analyte recovery under three different spiking levels was 64 100% with the relative standard deviations (RSD) below 8.19%. CONCLUSION: This simple and accurate method effectively eliminates false positive detection and can be used to determine the AFs in medicinal herbs to control product quality. We found that in the 174 samples tested, 27 were contaminated with AFs. The incidences of AFB1, AFB2, AFG1 and AFG2 in the samples tested were 15.52%, 14.37%, 6.32% and 2.30%, respectively. We proposed 10 ug/kg total AFs and 5 ug/kg AFB1 as the reasonable maximum limits (ML) in medicinal herbs, and there are 10 samples (5.71% occurrence) in our test that exceeded this proposed limit. PMID- 22323054 TI - Efficacy of estramustine phosphate according to risk classification of castration resistant prostate cancer. AB - Treatment options for patients who progressed to castration-resistant prostate cancer (CRPC) are very limited. The purpose of this study was to assess the efficacy of estramustine phosphate (EMP) in patients with CRPC, grouped according to the risk classification advocated by Armstrong et al. and to identify candidates for EMP treatment. Between March 2003 and July 2010, 82 patients with CRPC were treated with 280 or 560 mg EMP per os daily until disease progression or occurrence of unacceptable adverse events. Prostate-specific antigen (PSA) response and overall survival were evaluated according to risk classification. 52 (67%) patients achieved PSA decline. Rates of PSA decline in the good-, intermediate-, and poor-risk groups were 77, 71, and 25%, respectively, significantly higher in the good- and intermediate-risk groups than the poor-risk group (p=0.03). The median overall survival times in good-, intermediate-, and poor-risk groups were 21, 19, and 9 months, respectively (p=0.005 for good vs intermediate, p=0.001 for intermediate vs poor). When the intermediate-risk group was divided into two subgroups by PSA doubling time (PSADT), men with PSADT>=2 months achieved higher PSA response rate (88%) and longer survival (22 months) than those with PSADT<2 months (53%, 15 months). Patients with good-risk or intermediate-risk with PSA doubling time>=2 months achieved favourable PSA response and survival and may benefit from chemotherapy with EMP. PMID- 22323055 TI - "Straight-acting gays": the relationship between masculine consciousness, anti effeminacy, and negative gay identity. AB - Some gay men are preoccupied with traditional notions of masculinity and express negative feelings towards effeminate behavior in gay men. Various scholars have speculated that such attitudes by gay men reflect internalized negative feelings about being gay. Thus, we sought to assess the importance of masculinity among gay men, to compare their ideal versus perceived masculinity-femininity, to ask how gay men assess masculinity, and to test whether masculine consciousness and anti-effeminacy could predict negative feelings about being gay. Results from an online survey of 751 gay men in the United States (MAge=32.64 years, SD=11.94) showed that the majority rated masculinity for themselves and in a same-sex partner as important, and they ideally wished that their behavior was more masculine (Cohen's d=.42) and less feminine (d=.42) than they perceived it to be. Furthermore, one's behavior was more important than how one looks when assessing masculinity. A multiple regression analysis showed that the degree to which they were preoccupied with masculinity and expressed anti-effeminacy accounted for 30% of the variance in negative feelings about being gay. These finding further support the idea that masculinity is an important construct for gay men and that masculine consciousness and anti-effeminacy are related to negative feelings about being gay. PMID- 22323056 TI - Melatonin promotes angiogenesis during repair of bone defects: a radiological and histomorphometric study in rabbit tibiae. AB - OBJECTIVES: The pineal gland hormone, melatonin, is an immunomodulator and neuroendocrine hormone; it also stimulates monocyte, cytokine and fibroblast proliferations, which influence angiogenesis. The aim of this study was to investigate the effects of melatonin on angiogenesis during bone defect repair by means of radiological and histomorphometric evaluations of bone response to melatonin implants. MATERIALS AND METHODS: Twenty New Zealand rabbits weighing 3,900-4,500 g were used. Twenty melatonin implants were inserted in the proximal metaphyseal area of the animals' right tibia and 20 control areas were located in the left proximal metaphyseal area. Following implantation, the animals were sacrificed in groups of five, after 1, 2, 3 and 4 weeks, respectively. Anteroposterior and lateral radiographs were taken, and radiographic thermal imaging analysis was performed for all groups at different time stages following implant insertion. Samples were sectioned at 5 MUm and stained using Hematoxylin Eosin and Masson's trichrome, supplementing radiographic findings with histomorphometric analysis. RESULTS: After 4 weeks, radiological images showed complete repair of the bone defects. No healed or residual bone alterations attributable to the presence of the melatonin implant were observed. Histomorphometric analysis at 4 weeks showed the presence of a higher density newly formed bone. There were statistically significant differences in the length of cortical formation between the melatonin group and the control group during the first weeks of the study; there were also statistically significant differences in the number of vessels observed in the melatonin groups at the first two study stages. CONCLUSION AND CLINICAL RELEVANCE: Melatonin may have potential beneficial effects on bone defect repair. PMID- 22323058 TI - Suture fixation versus cable cerclage of the tuberosities in shoulder arthroplasty-clinical and radiologic results. AB - BACKGROUND: The most important individual parameter linked to functional outcome following hemiarthroplasty for fractures of the proximal humerus is anatomical healing of the tuberosities. The aim of our study was to evaluate whether the fixation method influences tuberosity healing and functional outcome. METHODS: Twenty-five consecutive patients with acute 4-part fractures of the proximal humerus were treated with hemiarthroplasty and cable fixation of the tuberosities. Twenty-nine previous patients with four-part fractures treated with hemiarthroplasty and suture fixation of the tuberosities were included as a control group. Functional evaluation was measured with the Constant Score 1 year after the operation. Radiographic evaluation included evaluation of the extent of tuberosity healing and head centralisation. RESULTS: The average Constant Score was 53.2 points in the suture group and 60.9 in the cable group (p = 0.29). An x ray evaluation revealed that 40% of the tuberosities in the suture group were anatomically healed versus 75% (p = 0.027) in the cable group. In the suture group, 44% of the prostheses showed marked superior migration, whereas 25% of the prostheses in the cable group showed such migration (p = 0.027). CONCLUSION: In our collective adding an encircling steel cable for the fixation of the tuberosities resulted in higher anatomical healing rates. PMID- 22323057 TI - Incidence of three roots and/or four root canals in the permanent mandibular first molars in a Korean sub-population. AB - OBJECTIVES: The purpose of this study was to evaluate the prevalence of three rooted permanent mandibular first molars (PMFMs) with four canals and their morphological characteristics among a Korean population from using cone-beam computed tomography scans (CBCTs). MATERIALS AND METHODS: Among the 705 CBCTs screened, 472 patient cases possessing at least one PMFM were identified. A total of 780 PMFMs were evaluated in axial section series to determine the number of roots and canals. The incidences of three-rooted PMFMs were compared with regard to gender and location. For distal root(s) with two canals, inter-orifice distances (IOD) between distobuccal and distolingual canals were measured at pulpal floor and furcation levels. The difference of IOD between males and females was also analyzed using chi-square tests. RESULTS: Among the 472 CBCTs of 225 females and 247 males, 84 females and 107 males were found to have at least one three-rooted PMFM. Among the 780 PMFMs, 191 PMFMs (24.5%, 89 of 397 left and 102 of 383 right) were found to have three roots. The prevalence of distal root(s) with two canals was 34.2% (267 of 780). From the molars with two distal canals, the mean IOD between distobuccal and distolingual canals at the pulpal floor level was 3.1 mm in males and 2.9 mm in females (p = 0.0428). CONCLUSIONS: The occurrence of three-rooted PMFMs among a Korean population was 24.5% and was higher than other countries and ethnicities. Understanding the prevalence of PMFMs with a distolingual root and/or canal in a Korean population and the IOD between distobuccal and distolingual canals may be useful for successful endodontic treatments. CLINICAL RELEVANCE: Acknowledgment of potential incidence of three-rooted permanent mandibular first molars with four canals and the distance between two distal canals may increase the success rate of root canal treatment by reducing the missing canal untreated. PMID- 22323059 TI - Development of a score set to measure function and quality of life in patients suffering from elbow pathology. AB - INTRODUCTION: Daily function plays an important role in the quality of life for patients suffering from pathology of the upper extremity. The recovery of functions of daily living determines the success or failure of the treatment for the patient. The goal of this study was to establish and validate a score set measuring quality of life, and objective and subjective function in general elbow pathologies. METHODS: A literature review was performed, in order to find a patient-based elbow specific questionnaire. The score set was tested and validated in a cross-sectional setting. RESULTS: The patient-rated elbow evaluation (PREE) was chosen as the patient-based elbow specific questionnaire. For measuring general health and subjective arm function, the short form-36 mental health (SF-36 MH) and the shortened disabilities of the arm, shoulder and hand questionnaire (quick DASH) were chosen, respectively. To measure objective function, several clinical tests were implemented. The score set was tested in 66 patients, of which 56.1% had function restrictions due to pain. The correlation between the PREE-function and quick DASH was found to be the highest (r = 0.74*). Between the PREE and quick DASH, the correlation was good (r = 0.70*) and between the PREE-pain and quick DASH, the correlation was moderate (r = 0.58*). The lowest correlation (r = 0.18) was found between the PREE and SF-36 MH (*p < 0.01). CONCLUSION: General health, subjective and objective function can be measured in elbow pathology patients using a score set containing the SF-36 MH, quick DASH, PREE, and several clinical tests. Further testing of the score set needs to be executed in a prospective study. PMID- 22323060 TI - Re: A prospective investigation of coffee drinking and endometrial cancer incidence. PMID- 22323061 TI - White bear everywhere: exploring the boundaries of the attentional white bear phenomenon. AB - Some failures of selective attention may be explained by the attentional white bear (AWB) phenomenon Tsal & Makovski (Journal of Experimental Psychology: Human Perception and Performance 32:351-363, 2006), which indicates that prior knowledge of a distractor location causes attention to be actively allocated to it. The AWB effect is demonstrated in a task that includes infrequent trials that involve two simultaneous dots embedded among flanker trials. The dot positioned at an expected distractor location is perceived as appearing before the dot at an expected empty location, indicating that attentional resources have initially been allocated to the expected distractor locations. The main goal of this study was to explore the boundaries of the AWB phenomenon by imposing perceptual, memory, and sensory constraints on the flanker task. The results showed that the AWB effect was obtained even when additional constraints severely taxed the information-processing system. We propose that a mandatory mechanism guides a fixed minimal amount of attention to expected distractor locations in a top-down manner. PMID- 22323062 TI - dbPTB: a database for preterm birth. AB - Genome-wide association studies (GWAS) query the entire genome in a hypothesis free, unbiased manner. Since they have the potential for identifying novel genetic variants, they have become a very popular approach to the investigation of complex diseases. Nonetheless, since the success of the GWAS approach varies widely, the identification of genetic variants for complex diseases remains a difficult problem. We developed a novel bioinformatics approach to identify the nominal genetic variants associated with complex diseases. To test the feasibility of our approach, we developed a web-based aggregation tool to organize the genes, genetic variations and pathways involved in preterm birth. We used semantic data mining to extract all published articles related to preterm birth. All articles were reviewed by a team of curators. Genes identified from public databases and archives of expression arrays were aggregated with genes curated from the literature. Pathway analysis was used to impute genes from pathways identified in the curations. The curated articles and collected genetic information form a unique resource for investigators interested in preterm birth. The Database for Preterm Birth exemplifies an approach that is generalizable to other disorders for which there is evidence of significant genetic contributions. PMID- 22323063 TI - The gene-specific codon counting database: a genome-based catalog of one-, two-, three-, four- and five-codon combinations present in Saccharomyces cerevisiae genes. AB - A codon consists of three nucleotides and functions during translation to dictate the insertion of a specific amino acid in a growing peptide or, in the case of stop codons, to specify the completion of protein synthesis. There are 64 possible single codons and there are 4096 double, 262 144 triple, 16 777 216 quadruple and 1 073 741 824 quintuple codon combinations available for use by specific genes and genomes. In order to evaluate the use of specific single, double, triple, quadruple and quintuple codon combinations in genes and gene networks, we have developed a codon counting tool and employed it to analyze 5780 Saccharomyces cerevisiae genes. We have also developed visualization approaches, including codon painting, combination and bar graphs, and have used them to identify distinct codon usage patterns in specific genes and groups of genes. Using our developed Gene-Specific Codon Counting Database, we have identified extreme codon runs in specific genes. We have also demonstrated that specific codon combinations or usage patterns are over-represented in genes whose corresponding proteins belong to ribosome or translation-associated biological processes. Our resulting database provides a mineable list of multi-codon data and can be used to identify unique sequence runs and codon usage patterns in individual and functionally linked groups of genes. PMID- 22323064 TI - First-order antiferro-ferromagnetic transition in Fe(49)(Rh(0.93)Pd(0.07))(51) under simultaneous application of magnetic field and external pressure. AB - A magnetic field-pressure-temperature (H-P-T) phase diagram for first-order antiferromagnetic (AFM) to ferromagnetic (FM) transitions in Fe(49)(Rh(0.93)Pd(0.07))(51) has been constructed using resistivity measurements under simultaneous application of magnetic field (up to 8 T) and pressure (up to 20 kbar). The temperature dependence of resistivity (rho-T) shows that the width of the transition and the extent of hysteresis decreases with pressure and increases with magnetic field. By exploiting opposing trends of dT(N)/dP and dT(N)/dH (where T(N) is the first-order transition temperature), the relative effects of temperature, magnetic field and pressure on disorder-broadened first order transitions has been studied. For this, a set of H and P values are chosen for which T(N)(H(1),P(1)) = T(N)(H(2),P(2)). Measurements for such combinations of H and P show that the temperature dependence of resistivity is similar, i.e. the broadening (in temperature) of transition as well as the extent of hysteresis remains independent of H and P. Isothermal magnetoresistance measurements under various constant pressures show that even though the critical field required for AFM-FM transition depends on applied pressure, the extent of hysteresis as well as transition width (in magnetic field) remains constant with varying pressure. PMID- 22323065 TI - Visibility and measurement of cesarean section scars in pregnancy: a reproducibility study. AB - OBJECTIVES: To evaluate the visibility of cesarean section (CS) scars by transvaginal sonography (TVS) in pregnant women, to apply a standardized approach for measuring CS scars and to test its reproducibility throughout the course of pregnancy. METHODS: In this observational cohort study, 320 consecutive pregnant women with a previous cesarean delivery were examined to assess scar visibility by two independent examiners. TVS was carried out at 11-13, 19-21 and 34-36 weeks' gestation. A scar was defined as visible when an area of hypoechogenicity representing myometrial discontinuity at the anterior wall of the lower uterine segment was identified. In a subset of patients (n = 111), visible scars were measured by two independent examiners in three dimensions: scar width, depth and length as well as the residual myometrial thickness (RMT). Descriptive analysis was used to assess scar visibility, and the intraclass correlation coefficient (ICC) was calculated to show the strength of absolute agreement between two examiners for scar measurements. For RMT, a cut-off of 2.4 mm was used and measurement agreement was assessed using Cohen's kappa coefficient. RESULTS: The scar was visible in 284/320 cases (88.8%). Visible scars were significantly associated with anteverted uteri (P < 0.0001). Both examiners had 100% agreement on scar visibility at 12 and 20 weeks' gestation, while agreement was 96% at 34 weeks. The intra- and interobserver agreements for scar measurements were generally good (ICC 0.86 and 0.89, respectively). The kappa coefficient for the RMT was 0.27 in the first trimester, compared with 0.51 and 0.72 in the second and third trimesters, respectively. CONCLUSION: CS scars remain visible in the majority of women throughout pregnancy. They can be reproducibly measured in three dimensions when assessed by TVS in all trimesters of pregnancy. The agreement between two observers for CS scar measurement can be considered good for the first trimester, compared with relatively moderate agreement for the second and third trimesters. PMID- 22323066 TI - FAST EDGE-FILTERED IMAGE UPSAMPLING. AB - We present a novel edge preserved interpolation scheme for fast upsampling of natural images. The proposed piecewise hyperbolic operator uses a slope-limiter function that conveniently lends itself to higher-order approximations and is responsible for restricting spatial oscillations arising due to the edges and sharp details in the image. As a consequence the upsampled image not only exhibits enhanced edges, and discontinuities across boundaries, but also preserves smoothly varying features in images. Experimental results show an improvement in the PSNR compared to typical cubic, and spline-based interpolation approaches. PMID- 22323067 TI - Clinical and radiologic outcomes of TLIF applications with or without pedicle screw: a double center prospective pilot comparative study. AB - STUDY DESIGN: Prospective cohort data by merging data from comparative studies. OBJECTIVE: This study aimed to compare clinical and radiologic outcomes of the transforaminal lumbar interbody fusion (TLIF) procedure with or without pedicle screw support in stable patients with a degenerative disease. SUMMARY OF BACKGROUND DATA: The unilateral lumbar interbody fusion technique has gained popularity in the management of many lumbar degenerative conditions requiring fusion. TLIF is routinely performed with the support of pedicle screws. The use of the TLIF procedure without pedicle screw support has not yet been reported. METHODS: Between February 2006 and May 2009, surgical decompression and fusion was performed in patients with lumbar degenerative conditions using the TLIF technique either with (n=30, group A) or without pedicle screw support (n=30, group B). The 2 groups had similar age, sex distribution, pain level, and pain history. In this prospective study, patients were followed for a mean period of 31 months (range, 22 to 38 mo). The mean age was 45.5 years (range, 29 to 78 y), and all patients had a disease involving a single intervertebral space. RESULTS: The female to male ratio was 19:11 and 18:12 in groups A and B, respectively. Pain and function were evaluated by the Oswestry disability index and visual analog scale. Pseudoarthrosis developed in 2 patients from group A and in 3 patients from group B. Although these 5 patients had insufficient fusion, they did show a clinical improvement. The mean duration of the operation was 110 and 73 minutes in groups A and B, respectively. The mean total amount of bleeding was 410 and 220 mL in groups A and B, respectively. Cage loosening did not occur in group A, but 1 patient in group B developed asymptomatic cage loosening limited to the endplates. Four patients in group A suffered sciatic pain because of the malposition of the screw, and 1 patient in group B had contralateral sciatic pain lasting for 2 months. The visual analog scale and Oswestry disability index scores were higher in group A than in group B 1 month after the operation (P<0.005), but the groups did not significantly differ at 3 months (P<0.89). The cost of the procedure was 3-fold higher in group A compared with group B. CONCLUSIONS: This study showed that the TLIF procedure without pedicle screw support would be sufficient in the management of preoperatively stable patients with lumbar degenerative spinal disease requiring fusion after single-level decompression. This technique is minimally invasive, requires only unilateral intervention, allows magnetic resonance imaging during the postoperative period and is associated with less costs and complications when compared with pedicle screwing. This study represents the first prospective comparative report on this technique showing several of its advantages. PMID- 22323068 TI - Expression of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and matrix metalloproteinases 1, 3, and 9 in hypertrophied ligamentum flavum. AB - STUDY DESIGN: Immunohistological study. OBJECTIVE: To elucidate the role of matrix metalloproteinases (MMPs), hypoxia-inducible factor-1alpha (HIF), and vascular endothelial growth factor (VEGF) in the hypertrophied ligamentum flavum (LF) obtained from patients with lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA: The most common spinal disorder in the elderly is LSS, which results in part from LF hypertrophy. Although prior histologic and immunochemical studies have been performed in this area, the pathophysiology of loss of elasticity and hypertrophy is not completely understood. METHODS: LF samples of 38 patients with LSS were harvested during spinal decompression. Twelve LF samples obtained from patients with disk herniation and no visible degeneration on preoperative magnetic resonance imaging were obtained as controls. Samples were dehydrated and paraffin embedded. For immunohistochemical determination of VEGF, HIF, and MMPs 1, 3, and 9 expression, slices were stained with VEGF, HIF, and MMP antibody dilution. Neovessel density and number of elastic fibers were counted after Masson-Goldner staining. LF hypertrophy and cross-sectional area (CSA) were measured on T1-weighted magnetic resonance imaging. RESULTS: MMPs 1, 3, 9 and VEGF expression were significantly increased in the hypertrophy group (P<0.05). HIF expression was negative in both groups. Vessel density was increased in the hypertrophy group, although this was not statistically significant. The number of elastic fibres was significantly higher in the control group. In the hypertrophy group, LF thickness was significantly increased, whereas CSA was significantly decreased. There was a statistical correlation between LF thickness, CSA, MMP, and VEGF expression in the hypertrophy group (P<0.05). CONCLUSIONS: LF hypertrophy is accompanied by increased MMPs 1, 3, 9 and VEGF expression. Neovessel density is increased in hypertrophied LF. HIF is not expressed in hypertrophied LF. PMID- 22323069 TI - New cervical compressive staple: in vitro testing and early clinical results. AB - STUDY DESIGN: In vitro testing and retrospective study. OBJECTIVE: To evaluate the biomechanical and preliminary clinical results of a staple. SUMMARY OF BACKGROUND DATA: Anterior cervical discectomy and fusion is currently the most used technique in cervical surgery. Arthrodesis is obtained with a spacer generally secured using a screwed osteosynthesis plate. Implantation of a plate is time consuming and exposes the patient to additional adverse events. The C JAWS device is a new cervical compressive staple developed to stabilize the spacer. METHODS: Intact and instrumented behaviors of 6 cervical segments were compared. Instrumentation consisted of a spacer and the staple, fixed at C5-C6 level. The 3-dimensional ranges of motion (ROM) of C5 regarding C6 was tracked. Twenty-three consecutive patients, with single-level cervical disc herniation, were reviewed retrospectively. All patients were treated with anterior cervical discectomy and fusion using a spacer secured by the staple. The Neck Disability Index score and Pain scores were reported; radiographic examinations were used to assess fusion. RESULTS: Mean ROM were 10 degrees, 8 degrees, and 10 degrees for the intact specimens and 4 degrees, 5 degrees, and 8 degrees for the instrumented ones in flexion-extension, lateral bending, and axial torsion, respectively. The mean clinical follow-up was 24.4 months. The mean operating time was 35 minutes. Patients showed sustained clinical improvement, and radiographic fusion was obtained at last follow-up. No clinical complication was reported except 1 hardware breakage for a borderline indication: the patient reported no complaint, and solid fusion was obtained. CONCLUSIONS: Experimental results showed reduced ROM of the instrumented spine regarding the intact one. Fusion rate and the occurrence of complication are similar to previous published data. The staple seems to provide a safe and effective new way to stabilize and secure a spacer with a short surgical time. A multicenter prospective clinical study, with more patients, is in progress to confirm these promising results. PMID- 22323070 TI - The legal risks of returning results of genomics research. AB - Published guidelines suggest that research results and incidental findings should be offered to study participants under some circumstances. Although some have argued against the return of results in research, many cite an emerging consensus that there is an ethical obligation to return at least some results; the debate quickly turns to issues of mechanics (e.g., which results? who discloses? for how long does the obligation exist?). Although commentators are careful to distinguish this as an ethical rather than legal obligation, we worry that return of results may unjustifiably become standard of care based on this growing "consensus," which could quickly lead to a legal (negligence-based) duty to offer and return individualized genetic research results. We caution against this and argue in this essay that the debate to date has failed to give adequate weight to a number of fundamental ethical and policy issues that should undergird policy on return of research results in the first instance, many of which go to the fundamental differences between research and clinical care. We confine our comments to research using data from large biobanks, the topic of the guidelines proposed in this symposium issue. PMID- 22323071 TI - Engaging children in genomics research: decoding the meaning of assent in research. AB - This article considers how to approach assent from children for genomics research. We examine the "protection" rationale for assent, which emerged in the context of a historical debate regarding whether it was ever acceptable to subject children to risks of research for the benefit of others. We also consider the "development" rationale for assent, which has been articulated for pediatric clinical practice, as an alternative approach for addressing this issue. We consider these rationales in light of the more recent literature on pediatric assent in the research context, and suggest that "engagement" is a more useful construct. This construct emphasizes that children have development capacities that should be respected and includes a limited role for assent to allow children to protect themselves. Engaging children does not require disclosure of all of the benefits and risks of genomics research that might be conveyed to an adult and may permit a degree of parental control over decisions. Using a construct that emphasizes respect can also justify asking children, as they approach adulthood, about their willingness to participate in ongoing genomics research, and yet also permit research to continue if some cannot be reached to obtain consent. PMID- 22323072 TI - Taxonomizing, sizing, and overcoming the incidentalome. AB - PURPOSE: With the advent of whole-genome sequencing made clinically available, the number of incidental findings is likely to rise. The false-positive incidental findings are of particular clinical concern. We provide estimates on the size of these false-positive findings and classify them into four broad categories. METHODS: Whole-genome sequences (WGS) of nine individuals were scanned with several comprehensive public annotation databases and average estimates for the number of findings. These estimates were then evaluated in the perspective of various sources of false-positive annotation errors. RESULTS: At present there are four main sources of false-positive incidental findings: erroneous annotations, sequencing error, incorrect penetrance estimates, and multiple hypothesis testing. Of these, the first two are likely to be addressed in the near term. Conservatively, current methods deliver hundreds of false positive incidental findings per individual. CONCLUSION: The burden of false positives in whole-genome sequence interpretation threatens current capabilities to deliver clinical-grade whole-genome clinical interpretation. A new generation of population studies and retooling of the clinical decision-support approach will be required to overcome this threat. PMID- 22323073 TI - Practical implementation issues and challenges for biobanks in the return of individual research results. AB - Whether or not to give research results back to individuals whose specimens are used for biomedical research is a subject of considerable controversy. Much of the debate has been focused around the ethical and legal concerns with some consideration of broader social issues such as whether or not people will be affected by such information for employment or health care. Much less attention has been paid to biobanks that collect the specimens used to generate the research findings and the issues and operational requirements for implementing return of individual research results. In this article, we give the biobanks' perspective and highlight that given the diversity among the types of biobanks, it may be difficult to design and implement a blanket policy in this complex area. We discuss the variability in the types of biobanks and some important issues that should be considered in determining whether or not research results should be provided to individuals whose specimens are used in biomedical research. We also discuss challenges that should be considered in implementing any approaches to the return of research results. PMID- 22323074 TI - Presence of GAD65 autoantibodies in the serum of children with autism or ADHD. AB - Antibodies against glutamic acid decarboxylase 65 (GAD65) have been detected in the serum of patients with several neurological disorders. The presence of antibodies against GAD65 has not yet been examined in the serum of patients with neurodevelopmental disorders such as autism or attention-deficit/hyperactivity disorder (ADHD). In this study, GAD65 antibodies and total IgG were assayed in the serum of normal subjects and patients diagnosed with autism or ADHD. GAD65 antibodies were detected in the serum of 15% of children with autism (N = 20), 27% of children with ADHD (N = 15) and of none of the controls (N = 14). The serum of 60% of autistic and 53% of ADHD patients reacted with Purkinje neurons in mouse cerebellum. Serum from 20% of ADHD patients reacted also with the cells in the molecular and granule cell layers and cells in the vicinity of the Purkinje neurons. No association was found between the titer of GAD65 antibodies and total IgG levels, and presence of seizures or mental retardation. None of the ADHD patients were diagnosed with mental retardation. Serum anti-GAD65 antibodies may be a common marker of subgroups of patients with autism and ADHD. Reactions of serum antibodies with the cells in the cerebellum in these patients suggest direct effects on brain function. The subgroup of children with autism and ADHD that tests positive for GAD65 antibodies needs further characterization in a larger study. PMID- 22323075 TI - Human papillomavirus types in 115,789 HPV-positive women: a meta-analysis from cervical infection to cancer. AB - Genotyping may improve risk stratification of high-risk (HR) human papillomavirus (HPV)-positive women in cervical screening programs; however, prospective data comparing the natural history and carcinogenic potential of individual HR types remain limited. A meta-analysis of cross-sectional HR HPV-type distribution in 115,789 HPV-positive women was performed, including 33,154 normal cytology, 6,810 atypical squamous cells of undetermined significance (ASCUS), 13,480 low-grade squamous intraepithelial lesions (LSIL) and 6,616 high-grade SIL (HSIL) diagnosed cytologically, 8,106 cervical intraepithelial neoplasia grade 1 (CIN1), 4,068 CIN2 and 10,753 CIN3 diagnosed histologically and 36,374 invasive cervical cancers (ICCs) from 423 PCR-based studies worldwide. No strong differences in HPV type distribution were apparent between normal cytology, ASCUS, LSIL or CIN1. However, HPV16 positivity increased steeply from normal/ASCUS/LSIL/CIN1 (20-28%), through CIN2/HSIL (40/47%) to CIN3/ICC (58/63%). HPV16, 18 and 45 accounted for a greater or equal proportion of HPV infections in ICC compared to normal cytology (ICC:normal ratios = 3.07, 1.87 and 1.10, respectively) and to CIN3 (ICC:CIN3 ratios = 1.08, 2.11 and 1.47, respectively). Other HR types accounted for important proportions of HPV-positive CIN2 and CIN3, but their contribution dropped in ICC, with ICC:normal ratios ranging from 0.94 for HPV33 down to 0.16 for HPV51. ICC:normal ratios were particularly high for HPV45 in Africa (1.85) and South/Central America (1.79) and for HPV58 in Eastern Asia (1.36). ASCUS and LSIL appear proxies of HPV infection rather than cancer precursors, and even CIN3 is not entirely representative of the types causing ICC. HPV16 in particular, but also HPV18 and 45, warrant special attention in HPV-based screening programs. PMID- 22323076 TI - Consensus statement of the ESICM task force on colloid volume therapy in critically ill patients. AB - PURPOSE: Colloids are administered to more patients than crystalloids, although recent evidence suggests that colloids may possibly be harmful in some patients. The European Society of Intensive Care Medicine therefore assembled a task force to compile consensus recommendations based on the current best evidence for the safety and efficacy of the currently most frequently used colloids--hydroxyethyl starches (HES), gelatins and human albumin. METHODS: Meta-analyses, systematic reviews and clinical studies of colloid use were evaluated for the treatment of volume depletion in mixed intensive care unit (ICU), cardiac surgery, head injury, sepsis and organ donor patients. Clinical endpoints included mortality, kidney function and bleeding. The relevance of concentration and dosage was also assessed. Publications from 1960 until May 2011 were included. The quality of available evidence and strength of recommendations were based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RECOMMENDATIONS AND CONCLUSIONS: We recommend not to use HES with molecular weight >= 200 kDa and/or degree of substitution >0.4 in patients with severe sepsis or risk of acute kidney injury and suggest not to use 6% HES 130/0.4 or gelatin in these populations. We recommend not to use colloids in patients with head injury and not to administer gelatins and HES in organ donors. We suggest not to use hyperoncotic solutions for fluid resuscitation. We conclude and recommend that any new colloid should be introduced into clinical practice only after its patient-important safety parameters are established. PMID- 22323077 TI - ECMO criteria for influenza A (H1N1)-associated ARDS: role of transpulmonary pressure. AB - PURPOSE: To assess whether partitioning the elastance of the respiratory system (E (RS)) between lung (E (L)) and chest wall (E (CW)) elastance in order to target values of end-inspiratory transpulmonary pressure (PPLAT(L)) close to its upper physiological limit (25 cmH(2)O) may optimize oxygenation allowing conventional treatment in patients with influenza A (H1N1)-associated ARDS referred for extracorporeal membrane oxygenation (ECMO). METHODS: Prospective data collection of patients with influenza A (H1N1)-associated ARDS referred for ECMO (October 2009-January 2010). Esophageal pressure was used to (a) partition respiratory mechanics between lung and chest wall, (b) titrate positive end expiratory pressure (PEEP) to target the upper physiological limit of PPLAT(L) (25 cmH(2)O). RESULTS: Fourteen patients were referred for ECMO. In seven patients PPLAT(L) was 27.2 +/- 1.2 cmH(2)O; all these patients underwent ECMO. In the other seven patients, PPLAT(L) was 16.6 +/- 2.9 cmH(2)O. Raising PEEP (from 17.9 +/- 1.2 to 22.3 +/- 1.4 cmH(2)O, P = 0.0001) to approach the upper physiological limit of transpulmonary pressure (PPLAT(L) = 25.3 +/- 1.7 cm H(2)O) improved oxygenation index (from 37.4 +/- 3.7 to 16.5 +/- 1.4, P = 0.0001) allowing patients to be treated with conventional ventilation. CONCLUSIONS: Abnormalities of chest wall mechanics may be present in some patients with influenza A (H1N1)-associated ARDS. These abnormalities may not be inferred from measurements of end-inspiratory plateau pressure of the respiratory system (PPLAT(RS)). In these patients, titrating PEEP to PPLAT(RS) may overestimate the incidence of hypoxemia refractory to conventional ventilation leading to inappropriate use of ECMO. PMID- 22323078 TI - Transpulmonary pressure as a surrogate of plateau pressure for lung protective strategy: not perfect but more physiologic. PMID- 22323079 TI - Moxifloxacin-induced rhabdomyolysis. PMID- 22323080 TI - Cardiac arrest in pregnancy: lessons to be learned! PMID- 22323081 TI - Increased nonbeneficial care in patients spending their birthday in the ICU. AB - OBJECTIVE: End-of-life decisions are based on objective and subjective criteria. Previous studies identified substantial subjective biases during end-of-life decision-making. We evaluated whether in-ICU patient's birthday influenced management decisions. DESIGN: We used a case-control design in which patients spending their birthday in the ICU (cases) were matched to controls on center, gender, age, severity, type of admission, and length of ICU stay before birthday. SETTING: 12 ICUs in French hospitals. PATIENTS: The cases and controls were patients with ICU admissions >48 h over a 10-year period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Compared with the 1,042 controls, the 223 cases were more often trauma patients and received a larger number and longer durations of life-sustaining interventions. This increased intensity of life support occurred after, but not before, the birthday. The cases had longer ICU stay lengths. ICU and hospital mortality were not different between the two groups. End-of-life decisions were made in 22% and 24% of cases and controls, respectively. However, these decisions were made later in the cases than in the controls (18 [5-33] versus 9 [3-19] days). CONCLUSIONS: Our finding that patients who spent their birthday in the ICU received a higher intensity of life sustaining care and had longer ICU stays but did not have significantly different mortality rates compared with the controls suggests the use of nonbeneficial interventions. Staff members caring for patients whose birthdays fall during the ICU stay should be aware that this feature can bias end-of-life decisions, leading to an inappropriate level of care. PMID- 22323082 TI - Small-molecule screen identifies modulators of EWS/FLI1 target gene expression and cell survival in Ewing's sarcoma. AB - Ewing's sarcoma family of tumors (EFT) is characterized by the presence of chromosomal translocations leading to the expression of oncogenic transcription factors such as, in the majority of cases, EWS/FLI1. Because of its key role in Ewing's sarcoma development and maintenance, EWS/FLI1 represents an attractive therapeutic target. Here, we characterize PHLDA1 as a novel direct target gene whose expression is repressed by EWS/FLI1. Using this gene and additional specific well-characterized target genes such as NROB1, NKX2.2 and CAV1, all activated by EWS/FLI1, as a read-out system, we screened a small-molecule compound library enriched for FDA-approved drugs that modulated the expression of EWS/FLI1 target genes. Among a hit-list of nine well-known drugs such as camptothecin, fenretinide, etoposide and doxorubicin, we also identified the kinase inhibitor midostaurin (PKC412). Subsequent experiments demonstrated that midostaurin is able to induce apoptosis in a panel of six Ewing's sarcoma cell lines in vitro and can significantly suppress xenograft tumor growth in vivo. These results suggest that midostaurin might be a novel drug that is active against Ewing's cells, which might act by modulating the expression of EWS/FLI1 target genes. PMID- 22323083 TI - Plant volatiles enhance behavioral responses of grapevine moth males, Lobesia botrana to sex pheromone. AB - Plant volatiles play an important role in the lives of phytophagous insects, by guiding them to oviposition, feeding and mating sites. We tested the effects of different host-plant volatiles on attraction of Lobesia botrana males to the female-produced sex pheromone, in a wind tunnel. Addition of volatile emissions from grapevines or individual plant volatiles to pheromone increased the behavioral responses of L. botrana males over those to pheromone alone. At a low release rate (under-dosed) of pheromone, addition of (E)-beta-caryophyllene, (Z) 3-hexenyl acetate, 1-hexanol, or 1-octen-3-ol increased all behavioral responses, from activation to pheromone source contact, while addition of (E)-4,8-dimethyl 1,3,7-nonatriene, (E)-beta-farnesene, (Z)-3-hexenol, or methyl salicylate affected only the initial behavioral responses. Dose-response experiments suggested an optimal release ratio of 1:1000 (sex pheromone: host plant volatile). Our results highlight the role of plant volatiles in the sensory ecology of L. botrana. PMID- 22323084 TI - CXCL12 mediates apoptosis resistance in rat C6 glioma cells. AB - The chemokine CXCL12/stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 regulate migration and patterning processes during brain development, but also contribute to proliferation and expansion of gliomas, the most malignant brain tumors. Recently, a previous orphan-receptor CXCR7/RDC-1 was discovered to be a second receptor for CXCL12. CXCR7 has been detected in normal brain parenchyma, but in particular in human brain tumors. However, little is known about the functional relevance of CXCR7. Since the well-characterized rat C6 glioma cell line is commonly used as a glioma model in vitro and in vivo, we investigated the expression, regulation and function of CXCL12 and its receptors in these tumor cells. Whereas CXCL12 and CXCR7 were transcribed at notable levels, CXCR4 was quite low. By sublethal doses of temozolomide, an alkylating drug commonly used in adjuvant glioma therapy, transcription of CXCL12 and its receptors were significantly induced. Decreased proliferation resulting from this sublethal treatment with temozolomide could be completely restored to normal proliferation rates by simultaneous stimulation with CXCL12. Similarly, CXCL12 protected C6 cells from apoptosis under treatment with higher temozolomide doses. Thus, the CXCL12-CXCR7 axis promotes glioma progression, and the rat C6 glioma cell line may be a useful model to further investigate these mechanisms in vitro and in vivo. PMID- 22323085 TI - Solid lipid nanoparticles with and without hydroxypropyl-beta-cyclodextrin: a comparative study of nanoparticles designed for colonic drug delivery. AB - New solid lipid nanoparticles (SLN), composed of Compritol ATO888 (C) and hydroxypropyl-beta-cyclodextrin (HP), were developed in order to study a new colon-specific formulation for diclofenac sodium (D) delivery. The prepared batches differ from each other by the molecular ratio between HP and D and by the composition of the matrix. Nanoparticles composed of an exclusively lipid matrix and nanoparticles with an oligomeric and lipid matrix were compared in order to establish the effect of both components on the drug delivery tests performed. The SLN preparation method was based on the oil/water hot homogenization process. Emulsions produced were cooled at room temperature and lyophilized in order to obtain dried nanoparticles; possible damage to nanoparticle shape and size was avoided by the addition of cryoprotectants to the aqueous dispersion of nanoparticles before exsiccation. An in vitro toxicity study was performed using CaCo(2) cells to establish the safety of the prepared SLN. Data obtained showed that production method studied guarantees emulsions composed of nanosized drops which can be dried by lyophilization into SLN with a size range of 300-600 nm. In vitro and ex vivo tests demonstrated that dried SLN can be considered as colon delivery systems; however, the matrix composition as well as the presence of cryoprotectant on their surface influences the release and permeation rate of D. The in vitro toxicity studies indicated that the SLN are well tolerated. PMID- 22323086 TI - Pulsed EPR characterization of encapsulated atomic hydrogen in octasilsesquioxane cages. AB - Hydrogen atoms encapsulated in molecular cages are potential candidates for quantum computing applications. They provide the simplest two-spin system where the 1s electron spin, S = 1/2, is hyperfine-coupled to the proton nuclear spin, I = 1/2, with a large isotropic hyperfine coupling (A = 1420.40575 MHz for a free atom). While hydrogen atoms can be trapped in many matrices at cryogenic temperatures, it has been found that they are exceptionally stable in octasilsesquioxane cages even at room temperature [Sasamori et al., Science, 1994, 256, 1691]. Here we present a detailed spin-lattice and spin-spin relaxation study of atomic hydrogen encapsulated in Si(8)O(12)(OSiMe(2)H)(8) using X-band pulsed EPR spectroscopy. The spin-lattice relaxation times T(1) range between 1.2 s at 20 K and 41.8 MUs at room temperature. The temperature dependence of the relaxation rate shows that for T < 60 K the spin-lattice relaxation is best described by a Raman process with a Debye temperature of theta(D) = 135 K, whereas for T > 100 K a thermally activated process with activation energy E(a) = 753 K (523 cm(-1)) prevails. The phase memory time T(M) = 13.9 MUs remains practically constant between 200 and 300 K and is determined by nuclear spin diffusion. At lower temperatures T(M) decreases by an order of magnitude and exhibits two minima at T = 140 K and T = 60 K. The temperature dependence of T(M) between 20 and 200 K is attributed to dynamic processes that average inequivalent hyperfine couplings, e.g. rotation of the methyl groups of the cage organic substituents. The hyperfine couplings of the encapsulated proton and the cage (29)Si nuclei are obtained through numerical simulations of field swept FID-detected EPR spectra and HYSCORE experiments, respectively. The results are discussed in terms of existing phenomenological models based on the spherical harmonic oscillator and compared to those of endohedral fullerenes. PMID- 22323087 TI - A new technique in double-bundle anterior cruciate ligament reconstruction using implant-free femoral fixation. AB - PURPOSE: The study is a prospective case-series analysis to demonstrate a new double bundle technique for anterior cruciate ligament (ACL) reconstruction with the use of hamstring tendons through a single tibial tunnel, a double femoral socket with implant-free femoral fixation and interference screw for tibial fixation. MATERIALS AND METHODS: Twenty-one patients were treated with the same technique. Hamstring tendons were not removed from the tibial side, and using a single tibial and a double femoral tunnel of 8 and 6 mm, respectively, anatomic ACL reconstruction was performed. Graft passage was performed from the tibial side to the posterolateral femoral tunnel and was looped back to the anteromedial femoral tunnel to be fixed on the tibial tunnel with an interference screw and additional extracortical fixation. Follow-up of the study group was performed for a two-year period, documenting standard clinical and radiographic parameters. RESULTS: Post-operative follow-up (mean 24 months) revealed radiological widening of tibial tunnel (mean 133.6%) in all patients and minor femoral tunnels widening (119.4% and 117.5%). Clinical evaluation showed no signs of instability, and knee evaluation using the IKDC score was performed. CONCLUSION: The manuscript describes a novel technique in ACL reconstruction, and reports the radiographic results of tunnel widening and clinical scores. Implant-free femoral fixation led to minor tunnel widening similar to previously published data. Further studies need to be performed to compare the long-term results with different published techniques of cost-effective implant-free ACL reconstruction. PMID- 22323088 TI - The phylotypic stage as a boundary of modular memory: non mechanistic perspective. AB - The concept of the phylotypic stage has been strongly integrated into developmental biology, thanks mostly to drawings presented by Haeckel (Anthropogenie oder Entwicklungsgeschichte des Menschen, 1874). They are printed in every textbook as proof of the existence of the phylotypic stage and the fact of its conservation, albeit many times criticized as misleading and simplifying (Richardson in Develop Biol 172:412-421, 1995, Richardson et al. in Anat Embryo 196:91-106, 1997; Bininda-Emons et al. in Proc R Soc Lond 270:341-346, 2003). Although generally accepted by modern biology, doubt still exists concerning the very existence or the usefulness of the concept. What kind of evolutionary and developmental horizons does it open indeed? This article begins with the history of the concept, discusses its validity and draws this into connotation with the idea of a memory activated throughout the development. Barbieri (The organic codes. An introduction to semantic biology, 2003) considers the phylotypic stage to be a crucial boundary when the genetic program ceases to suffice for further development of the embryo, and supracellular memory of the body plan is activated. This moment clearly coincides with the commencing of the modular development of the embryo. In this article the nature of such putative memory will be discussed. PMID- 22323089 TI - Effects of compression therapy and antibiotics on lymphatic flow and chronic venous leg ulceration. PMID- 22323090 TI - Working memory can enhance unconscious visual perception. AB - We demonstrate that unconscious processing of a stimulus property can be enhanced when there is a match between the contents of working memory and the stimulus presented in the visual field. Participants first held a cue (a colored circle) in working memory and then searched for a brief masked target shape presented simultaneously with a distractor shape. When participants reported having no awareness of the target shape at all, search performance was more accurate in the valid condition, where the target matched the cue in color, than in the neutral condition, where the target mismatched the cue. This effect cannot be attributed to bottom-up perceptual priming from the presentation of a memory cue, because unconscious perception was not enhanced when the cue was merely perceptually identified but not actively held in working memory. These findings suggest that reentrant feedback from the contents of working memory modulates unconscious visual perception. PMID- 22323091 TI - Rapid profiling of intact glucosinolates in Arabidopsis leaves by UHPLC-QTOFMS using a charged surface hybrid column. AB - INTRODUCTION: The analysis of glucosinolates (GS) is traditionally performed by reverse-phase liquid chromatography coupled to ultraviolet detection after a time consuming desulphation step, which is required for increased retention. Simpler and more efficient alternative methods that can shorten both sample preparation and analysis are much needed. OBJECTIVE: To evaluate the feasibility of using ultrahigh-pressure liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOFMS) for the rapid profiling of intact GS. METHODOLOGY: A simple and short extraction of GS from Arabidopsis thaliana leaves was developed. Four sub-2 um reverse-phase columns were tested for the rapid separation of these polar compounds using formic acid as the chromatographic additive. High-resolution QTOFMS was used to detect and identify GS. RESULTS: A novel charged surface hybrid (CSH) column was found to provide excellent retention and separation of GS within a total running time of 11 min. Twenty-one GS could be identified based on their accurate mass as well as isotopic and fragmentation patterns. The method was applied to determine the changes in GS content that occur after herbivory in Arabidopsis. In addition, we evaluated its applicability to the profiling of other Brassicaceae species. CONCLUSION: The method developed can profile the full range of GS, including the most polar ones, in a shorter time than previous methods, and is highly compatible with mass spectrometric detection. PMID- 22323092 TI - Activated partial thromboplastin time measurement is not associated with clinical outcomes in patients with high-risk non-ST-segment elevation acute coronary syndromes treated with unfractionated heparin. AB - Our objective was to determine the association of activated partial thromboplastin time (aPTT) with recurrent ischemic events and non-coronary artery bypass surgery-related thrombolysis in myocardial infarction major bleeding. We studied 4,985 patients with high-risk non-ST-segment elevation acute coronary syndromes (NSTE ACS) participating in SYNERGY, a prospective, randomized, international trial designed to emulate contemporary practice wherein unfractionated heparin (UFH) is given intravenously and titrated according to a weight-adjusted dosing nomogram to a target aPTT of 1.5-2 times the upper limit of normal (approximately 50-70 s). Aspirin was administered to 95% of patients, clopidogrel to 63%, and glycoprotein IIb/IIIa receptor inhibitors to 58%. More than 90% of patients underwent early coronary angiography, and 69% were revascularized. Used as a time-dependent covariate, aPTT was evaluated as a predictor of time to ischemic or major hemorrhagic events in proportional hazards regression models. Using discrete variable analysis, aPTT was categorized as persistently below a lower threshold of anticoagulation (<50 vs. >=50 s) for recurrent ischemic events and above an upper threshold (>70 vs. <=70 s) for major hemorrhagic events. UFH treatment lasted a median of 42 (30, 78) h. At >6-12 (n = 3,021), >12-24 (n = 3,406), and >24-48 (n = 2,497) h, 34, 41, and 46% of patients achieved the target aPTT range, respectively. Both before and after adjusting for baseline predictors of anticoagulant response and risk score (age, hypertension, diabetes, smoking, ST depression, and renal function), no significant relationship between aPTT values and recurrent ischemic events or major bleeding was found. No relationship was observed between clinical outcomes and aPTT values persistently above or below the designated thresholds. Measurements of aPTT were not associated with clinical outcomes among patients with NSTE ACS treated with UFH. The required intensity of anticoagulation for benefit may be relatively modest when UFH is administered concomitantly with dual or triple platelet directed therapy, particularly in patients undergoing early coronary revascularization. PMID- 22323094 TI - Does the presence of a cesarean section scar influence the site of placental implantation and subsequent migration in future pregnancies: a prospective case control study. AB - OBJECTIVES: To describe placental location in the first trimester of pregnancy and subsequent placental migration in women with and without a history of previous cesarean delivery. METHODS: In this prospective case-control study, placental location was defined according to five anatomical sites in relation to the endometrial cavity. Placental localization was carried out by transabdominal ultrasound between 11 and 14 weeks' gestation. We recruited 738 women who had undergone one or more previous cesarean sections (CS) and 1856 patients without previous cesarean delivery. Comparative analysis was performed of placental location between the two groups, and to assess placental migration of those classified as being low lying at 20 and 32 weeks' gestation. RESULTS: There were significant differences in placental location between the two groups. In the CS group there were significantly more posterior and fewer fundal placentae than in the control group (47.2 vs 31.5% and 4.7 vs 15.5%, respectively). The number of previous cesarean deliveries did not have a significant effect on placental location. There was no significant difference in the incidence of anterior low lying placenta between groups (1.5 vs 0.9%). Placental migration of the low-lying subtypes was similar in both groups (62 vs 64%). CONCLUSION: The presence of CS scars in the uterus are associated with an increase in the number of posterior placentae and a reduced number that implant in the fundus of the cavity. Migration of a low-lying placenta is independent of the presence of a CS scar in the uterus. PMID- 22323095 TI - Molecular targeted therapies for cancer: sorafenib mono-therapy and its combination with other therapies (review). AB - Sorafenib is an oral multikinase inhibitor that acts by inhibiting tumor growth and disrupting tumor microvasculature through antiproliferative, anti-angiogenic and proapoptotic effects. It exerts these effects via inhibition of multiple targets including Raf serine/threonine kinases, vascular endothelial growth factor receptor tyrosine kinases; VEGFR-1, VEGFR-2, VEGFR-3 and platelet-derived growth factor receptor beta (PDGFR-beta). Current literature shows that the deregulated signaling through these receptors is commonly seen in human tumors. In addition, sorafenib is also shown to induce apoptosis through downregulation of Mcl-1 in many cancer types. Hence, sorafenib as a single agent has shown promising activity in some cancers such as renal cell carcinoma (RCC), hepatocellular carcinoma (HCC) and thyroid cancers. Currently, the drug holds FDA approval for the treatment of advanced RCC and unresectable HCC. However, many clinical studies have indicated several limitations to the application of sorafenib as a single agent in various other cancers. Owing to these reasons and the potential of sorafenib to synergize with other anticancer therapies, its combination with other targeted agents and chemotherapy has been widely explored with promising results. In addition, it has also shown synergistic results when combined with radiation. This review summarizes the current basic and clinical studies on the effects and mechanisms of sorafenib either administered alone or in combination with other anticancer treatments. PMID- 22323096 TI - Long-chain polyunsaturated fatty acid levels in US donor human milk: meeting the needs of premature infants? AB - OBJECTIVE: To determine fatty acid levels in the US donor milk supply. STUDY DESIGN: Donor human milk samples from Iowa (n=62), Texas (n=5), North Carolina (n=5) and California (n=5) were analyzed by gas chromatography. Levels in the Iowa donor milk were compared before and after pasteurization using Student's t test. Docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels were compared among all milk banks using analysis of variance. RESULT: ARA (0.4 pre, 0.4 post, P=0.18) and DHA (0.073 pre, 0.073 post, P=0.84) were not affected by pasteurization. DHA varied between banks (P<0.0001), whereas ARA did not (P=0.3). DHA levels from all banks were lower than published values for maternal milk and infant formula (P<0.0001). CONCLUSION: Pasteurization of breastmilk does not affect DHA or ARA levels. However, DHA content in US donor milk varies with bank location and may not meet the recommended provision for preterm infants. PMID- 22323097 TI - Crystallization, spectral, crystallographical, and thermoanalytical studies of succinobucol polymorphism. AB - Four different polymorphs, A, C, D, and E, of succinobucol were isolated and characterized by means of solid-state nuclear magnetic resonance spectroscopy, single crystal and powder X-ray diffraction, differential scanning calorimetry, thermogravimetry, and attenuated total reflection-infrared spectroscopy. From a number of experiments, the same polymorphs (C, D, and E) and an equilibrium phase mixture B consisting of polymorphs C and D were repeatedly gained using different solvents or their mixtures. Although polymorph A was obtained directly from recrystallization only on few occasions, polymorphs C, D, and E proved to be metastable kinetic polymorphs, which slowly transform to a thermodynamically more stable form A during long-term storage. The single-crystal structures of polymorph C and D were determined by X-ray single-crystal diffraction. PMID- 22323098 TI - A new quantitative method for pivot shift grading. AB - PURPOSE: The purposes of the study were to evaluate and to quantify the pivot shift phenomenon by using a small and easy to handle measuring device for pivot shift quantification. METHODS: Twenty patients (forty knees) with primary torn anterior cruciate ligaments (ACL) were tested under anesthesia, graded by the examiner and by the device according to the IKDC classification [normal (0), glide (1), clunk (2), and gross (3)]. For the grading by the device, a femoral and a tibial miniature inertial sensor measured the acceleration and the angular velocities. Three parameters were used for pivot shift identification and quantification: (1) difference between the positive and negative acceleration peak value (a(diff)), (2) the maximum jerk (j(max)), and (3) the standard deviation (SD(a)) of the acceleration. The ratio between the ACL-deficient and the intact knees was calculated in order to normalize the data. RESULTS: The pivot shift phenomenon could be identified, and all three parameters showed significant higher values in the ACL-deficient knees compared to the intact knees (p < 0.05). The grading by examiner did not significantly correlate with a(diff) (p = 0.38; r = 0.21), j(max) (p = 0.36; r = -0.22), SD(a) (p = 0.65; r = 0.11), and grading by the device (p = 0.62; r = 0.12). CONCLUSIONS: The present study has shown that the quantification of the pivot shift test is practicable when inertial sensors are used. The results have shown that the subjective grading of the pivot shift test does not correlate well with objective quantification. PMID- 22323099 TI - Fifty communities putting prevention to work: accelerating chronic disease prevention through policy, systems and environmental change. AB - The burden of preventable chronic diseases is straining our nation's health and economy. Diseases caused by obesity and tobacco use account for the largest portions of this preventable burden. CDC funded 50 communities in 2010 to implement policy, systems, and environmental (PSE) interventions in a 2-year initiative. Funded communities developed PSE plans to reduce obesity, tobacco use, and second-hand smoke exposure for their combined 55 million residents. Community outcome objectives and milestones were categorized by PSE interventions as they related to media, access, promotion, pricing, and social support. Communities estimated population reach based on their jurisdiction's census data and target populations. The average proportion of each community's population that was reached was calculated for each intervention category. Outcome objectives that were achieved within 12 months of program initiation were identified from routine program records. The average proportion of a community's jurisdictional population reached by a specific intervention varied across interventions. Mean population reach for obesity-prevention interventions was estimated at 35%, with 14 (26%) interventions covering over 50% of the jurisdictional populations. For tobacco prevention, mean population reach was estimated at 67%, with 16 (84%) interventions covering more than 50% of the jurisdictional populations. Within 12 months, communities advanced over one-third of their obesity and tobacco-use prevention strategies. Tobacco interventions appeared to have higher potential population reach than obesity interventions within this initiative. Findings on the progress and potential reach of this major initiative may help inform future chronic disease prevention efforts. PMID- 22323100 TI - Factors associated with utilization of insecticide-treated nets in children seeking health care at a Ugandan hospital: perspective of child caregivers. AB - In Uganda malaria causes more morbidity and mortality than any other disease and children below 5 years contribute the biggest percentage of malaria related mortality. Insecticide treated nets (ITNs) are currently one of the most cost effective option for reducing malaria-related morbidity and mortality, however the factors affecting their utilization in Uganda are still not well understood. This study examined the prevalence and factors associated with ITN utilization among children of age 0-12 years seeking health care from a Ugandan hospital using caregiver's reports. A cross sectional design was used to collect data using a semi-structured questionnaire from 418 participants. Binary logistic regression was employed to determine predictors of ITN utilization. Results show that the prevalence of ITN utilization among children seeking health care was 34.2%. ITN utilization was higher among children of age <5 years [37.0, 95% CI 31.81-42.21] as compared to children aged >=5 years [22.9, 95% CI 13.77-32.01]. Source of mosquito net (OR = 13.53, 95% CI = 6.47-28.27), formal employment by head of household (OR = 6.00, 95% CI = 1.95-18.48), sharing a bed with parent (s) (OR = 2.61, 95% CI = 1.21-5.63) and number of children below 12 years in a household (OR = 0.80, 95% CI = 0.65-0.99), were significant predictors of utilization. ITN utilization among children was below the set national target. The predictors identified by this study reveal opportunities that can be taken advantage of by malaria control programs to achieve the desired rates of utilization and subsequently malaria prevention in children. PMID- 22323101 TI - Click-mediated labeling of bacterial membranes through metabolic modification of the lipopolysaccharide inner core. PMID- 22323102 TI - Neglected intussusception presenting as transanal prolapse of small bowel. AB - Although transanal prolapse of intussusception in infants is well recognized, it is rarely reported and confusion with rectal prolapse often results in delayed diagnosis and treatment. This report highlights the problems of delayed diagnosis and the morbidity and mortality associated with this condition. The authors report a case of 9 mo old boy who presented with prolapsing small bowel mimicking rectal prolapse. PMID- 22323103 TI - Immunization of HIV infected children. AB - Immunization is one of the most effective approaches to reduce morbidity and mortality in HIV infected children. However, progressive immune suppression may lead to impaired responsiveness to most of the vaccines. Besides this, there are many other areas of concern in these children including risk of diseases and safety issues with live vaccines, need for increased amount or number of doses of a particular vaccine, shortened duration of protective efficacy, need for revaccination after immune reconstitution and effect of vaccines on HIV viral replication. Published literature on safety, effectiveness and immunogenicity of vaccines in HIV infected children and status of individual vaccines with existing guidelines has been discussed in present review. PMID- 22323104 TI - Audiological correlates of tumor parameters in acoustic neuromas. AB - The objective of this study was undertaken to evaluate a correlation of pure tone audiometry, speech audiometry with tumor size, the presence of intrameatal extension, contralateral pure tone audiometry, and contralateral speech audiometry results at acoustic neuroma (AN) patients. Seventy-six patients with a unilateral-cerebellopontine angel tumor with/without internal acoustic canal (IAC) were included in this study. Data on pure tone audiometry, speech discrimination scores (SDS), speech reception thresholds (SRT), tumour size, and extension to IAC were analyzed retrospectively. As a result, patients with unilateral ANs had an asymmetric sensorineural hearing loss and had an asymmetric finding on the results of speech audiometry was present. We could not find any correlation between the size of the tumor and the hearing levels at each frequency. In addition, there appeared to be no significant correlation between the extension of tumor to the IAC and the audiological findings. PMID- 22323105 TI - Migration processes, familial characteristics, and schooling dropout among black youths. AB - This study uses data from the 2000 U.S. census to examine whether the schooling advantage of black immigrants' children found in previous studies is robust. According to the results, the advantage associated with having migrant parents is not restricted to the children of immigrants. Black migrant parents, regardless of foreign-born status, have children with favorable schooling outcomes. Such parental-level influences, however, seem stronger among some immigrant groups than among native internal migrants. The study also suggests that the collective advantage of the children of immigrants is driven by positive migrant selectivity. Accordingly, comparisons between the children of native migrants and children in various immigrant groups reveal that the immigrant advantage is not robust. In fact, the results suggest that when immigrant ethnicity is considered, some children of immigrants may be disadvantaged relative to the children of native migrants. Among recent migrants, the children of native internal migrants also have more favorable outcomes than the children of immigrants, although these differences disappear after background factors are controlled. Further, internal migrant and immigrant households are less likely to have characteristics that adversely affect schooling than nonmigrant households. Unsurprisingly, the children of nonmigrants have the worst outcomes among black youths. PMID- 22323106 TI - Fattening performance, carcass and meat quality characteristics of Kivircik male lambs. AB - The objective of this study was to determine the fattening performance and carcass and meat quality characteristics of Kivircik twin male lambs. Twelve lambs at approximately 5 months of age were subjected to a finishing diet for 60 days. Average live weight of lambs at the beginning and the end of the fattening were 23.14 +/- 0.84 and 39.0 +/- 1.01 kg, respectively. Daily live weight gain and feed conversion efficiency were found as 0.265 +/- 0.007 and 6.14 kg, respectively. Hot carcass weight, cold carcass weight, and dressing percentage were 19.6 +/- 0.6 and 18.9 +/- 0.6 kg and 48.1 +/- 0.3%, respectively. Kidney pelvic fat weight, internal fat weight, and m. longissimus dorsi area were 0.117 +/- 0.023 and 0.364 +/- 0.041 kg and 15.26 +/- 0.70 cm(2), respectively. The percentages of leg, back loin, forearm, shoulder, neck, flank-chest, kidney pelvic fat, and internal fat in carcasses of the lambs were found as 34.1 +/- 0.4%, 19.6 +/- 0.3%, 21.0 +/- 0.2%, 7.0 +/- 0.3%, 10.5 +/- 0.3%, 7.2 +/- 0.2%, 1.3 +/- 0.1%, and 1.8 +/- 0.1%, respectively. Averages water content, ash, protein content, and fat content of meat samples were 73.4%, 1.0%, 19.5% and 3.6%, respectively. pH and thiobarbituric acid reactive substances values of meat samples were 5.55 and 0.056 +/- 0.017. L*(lightness), a*(redness), and b*(yellowness) values were recorded as 43.87, 12.69, and 10.22, respectively. Thus, we conclude that fattening performance, carcass, and meat quality of Kivircik lambs are satisfactory levels than that of other native breeds. PMID- 22323107 TI - Enhanced conversion efficiency and surface hydrophobicity of nano-roughened Teflon-like film coated poly-crystalline Si solar cells. AB - Nano-roughened Teflon-like film coated poly-crystalline Si photovoltaic solar cells (PVSCs) with enhanced surface hydrophobicity and conversion efficiency (eta) are characterized and compared with those coated by a Si nanorod array or a standard SiN anti-reflection layer. The Teflon-like film coated PVSC surface reveals a water contact angle increasing from 89.3 degrees to 96.2 degrees as its thickness enlarges from 22 to 640 nm, which is much larger than those of the standard and Si nanorod array coated PVSC surfaces (with angles of 55.6 degrees and 32.8 degrees , respectively). After nano-roughened Teflon-like film passivation, the PVSC shows a comparable eta(10.89%) with the standard SiN coated PVSC (eta = 11.39%), while the short-circuit current (I(SC)) is slightly reduced by 2% owing to the slightly decreased UV transmittance and unchanged diode performance. In contrast, the Si nanorod array may offer an improved surface anti reflection with surface reflectance decreasing from 30% to 5% at a cost of optical scattering and randomized deflection, which simultaneously decrease the optical transmittance from 15% to 3% in the visible region without improving hydrophobicity and conversion efficiency. The Si nanorod array covered PVSC with numerous surface dangling bonds induced by 1 min wet-etching, which greatly reduces the open-circuit voltage (V(OC)) by 10-15% and I(SC) by 30% due to the reduced shunt resistance from 3 to 0.24 kOmega. The nano-scale roughened Teflon like film coated on PVSC has provided better hydrophobicity and conversion efficiency than the Si nanorod array covered PVSC, which exhibits superior water repellant performance and comparable conversion efficiency to be one alternative approach for self-cleaning PVSC applications. PMID- 22323109 TI - Assessing the potential for salmon recovery via floodplain restoration: a multitrophic level comparison of dredge-mined to reference segments. AB - Pre-restoration studies typically focus on physical habitat, rather than the food base that supports aquatic species. However, both food and habitat are necessary to support the species that habitat restoration is frequently aimed at recovering. Here we evaluate if and how the productivity of the food-base that supports fish production is impaired in a dredge-mined floodplain within the Yankee Fork Salmon River (YFSR), Idaho (USA); a site where past restoration has occurred and where more has been proposed to help recover anadromous salmonids. Utilizing an ecosystem approach, we found that the dredged segment had comparable terrestrial leaf and invertebrate inputs, aquatic primary producer biomass, and production of aquatic invertebrates relative to five reference floodplains. Thus, the food-base in the dredged segment did not necessarily appear impaired. On the other hand, we observed that off-channel aquatic habitats were frequently important to productivity in reference floodplains, and the connection of these habitats in the dredged segment via previous restoration increased invertebrate productivity by 58%. However, using a simple bioenergetic model, we estimated that the invertebrate food-base was at least 4* larger than present demand for food by fish in dredged and reference segments. In the context of salmon recovery efforts, this observation questions whether additional food-base productivity provided by further habitat restoration would be warranted in the YFSR. Together, our findings highlight the importance of studies that assess the aquatic food base, and emphasize the need for more robust ecosystem models that evaluate factors potentially limiting fish populations that are the target of restoration. PMID- 22323110 TI - Chemical composition of South American Burseraceae non-volatile oleoresins and preliminary solubility assessment of their commercial blend. AB - INTRODUCTION: Non-volatile oleoresins from neotropical Burseraceae are traditionally used for craft, technological and medicinal purposes. The crude resin is usually sold in popular markets of the forest communities. Adding value to this rainforest raw material requires establishing its composition. OBJECTIVE: To analyse the resin composition from different Burseraceae species and establish a minimally reproducible profile by gas chromatography, in order to parameterise its quality control. METHODOLOGY: Crude oleoresin samples of 10 Protium and Trattinnickia species and a commercial blend were subjected to hydrodistillation to remove volatile compounds. The chloroform-soluble residues were methylated, analysed by GC-FID (flame ionisation detection), and individual components were identified by analysing their mass fragmentation pattern in GC-MS and comparison with data from the literature. The blend solubility was assayed in 30 non chlorinated solvents at three different proportions. RESULTS: The resins consisted exclusively of triterpenes, showing a common predominance of four major compounds in all the samples, corresponding to alpha-amyrin, beta-amyrin, alpha amyrenone and beta-amyrenone. This profile was complemented with minor amounts of the tetracyclic beta-elemolic and alpha-elemolic acids, maniladiol, brein and other oxidised trace compounds. The better solvents for the resin were those chemically bearing more than four carbon atoms, as n-butyl acetate, 2 ethoxyethanol and isopropanol. The crude resin blend sold contained around 10% of insoluble material that was constituted by up to 70% inorganic residues mixed with humic acid derivatives, as attested by ash analysis and IR spectroscopy, respectively. CONCLUSION: The experimental results, complemented by a general inspection of the literature, demonstrated a systematically reproducible triterpene profile in Protium and Trattinnickia species. PMID- 22323111 TI - Three-dimensional power Doppler ultrasound for the study of cervical cancer and precancerous lesions. AB - OBJECTIVE: To evaluate the blood flow characteristics of the cervix in normal women and in women with cervical precancerous lesions or cervical cancer. METHODS: We studied 165 women with three-dimensional power Doppler ultrasound (3D PDU), of whom 71 had cervical cancer, 61 had precancerous lesions and 33 were healthy controls. The cervix was manually traced in the stored volumes using 15 degrees rotation steps and the following 3D-PDU indices were calculated: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). These indices were compared among the study groups and were also correlated with features of the precancerous lesions group and cancer group. RESULTS: The three indices were all statistically significantly higher in the cervical cancer group and precancerous lesions group than in controls (P < 0.001). In addition, significantly higher values of all indices were found in the cervical cancer group than in the precancerous lesions group (P < 0.001). Further analysis according to patient characteristics in the cancer group showed that VI, FI and VFI were not significantly different in relation to grade, histology, presence of positive lymph nodes or lymphovascular space involvement (P > 0.05). However, VI was significantly higher in patients with Stages IIIB-IV cancer than in patients with less advanced disease (P = 0.045). In the cervical cancer group there was a significant positive correlation between 3D-PDU indices and cervical volume. CONCLUSION: 3D-PDU assessment of the cervix reveals significant differences in all indices studied between women with cervical precancerous lesions or cancer and healthy women. In women with cervical cancer, an advanced stage is associated with higher VI, but 3D-PDU indices are not related to other pathological characteristics. PMID- 22323112 TI - Osteoconductivity and osteoinductivity of NanoFUSE((r)) DBM. AB - Bone graft substitutes have become an essential component in a number of orthopedic applications. Autologous bone has long been the gold standard for bone void fillers. However, the limited supply and morbidity associated with using autologous graft material has led to the development of many different bone graft substitutes. Allogeneic demineralized bone matrix (DBM) has been used extensively to supplement autograft bone because of its inherent osteoconductive and osteoinductive properties. Synthetic and natural bone graft substitutes that do not contain growth factors are considered to be osteoconductive only. Bioactive glass has been shown to facilitate graft containment at the operative site as well as activate cellular osteogenesis. In the present study, we present the results of a comprehensive in vitro and in vivo characterization of a combination of allogeneic human bone and bioactive glass bone void filler, NanoFUSE((r)) DBM. NanoFUSE((r)) DBM is shown to be biocompatible in a number of different assays and has been cleared by the FDA for use in bone filling indications. Data are presented showing the ability of the material to support cell attachment and proliferation on the material thereby demonstrating the osteoconductive nature of the material. NanoFUSE((r)) DBM was also shown to be osteoinductive in the mouse thigh muscle model. These data demonstrate that the DBM and bioactive glass combination, NanoFUSE((r)) DBM, could be an effective bone graft substitute. PMID- 22323113 TI - Frequent IDH1/2 mutations in intracranial chondrosarcoma: a possible diagnostic clue for its differentiation from chordoma. AB - Mutations in the genes encoding isocitrate dehydrogenase (IDH) 1/2 have been detected in a significant proportion of diffuse gliomas and in a small fraction of acute myeloid leukemia (AML) cases. Recently, in an examination of various types of mesenchymal tumor, IDH1/2 mutations were only found in cartilaginous tumors including central conventional and periosteal enchondromas/chondrosarcomas. The frequency of IDH1/2 mutations was 56%, and the IDH1 R132C mutation, which is not common in diffuse gliomas or AML, accounted for 40% of these mutations. In this study, we investigated the IDH1/2 mutation status of intracranial chondrosarcomas and chordomas, which are morphologically similar and affect similar regions of the cranial cavity. Of the 13 chondrosarcomas analyzed, six (46.1%) displayed IDH1/2 mutations (the predominant type was IDH1 R132C). Also, an IDH2 mutation (R172S) was observed in one case. Conversely, none of the ten chordomas analyzed displayed any IDH1 or IDH2 mutations. Our data suggest that the IDH1/2 mutation status could be valuable for distinguishing intracranial chondrosarcomas from chordomas. PMID- 22323114 TI - CRTC1-MAML2 gene fusion in mucoepidermoid carcinoma of the lacrimal gland. AB - Epithelial tumors of the lacrimal gland are histologically similar to salivary gland tumors. Here we report on a rare case of mucoepidermoid carcinoma (MEC) in a 73-year-old man with a swelling of the left lacrimal gland. The tumor had a microscopic appearance consistent with a classical low-grade MEC of the lacrimal gland. There were no signs of recurrence or metastases during a five-year follow up. Using RT-PCR and FISH we demonstrated that the tumor was positive for the CRTC1-MAML2 gene fusion previously shown to be associated with in particular low grade salivary MECs with favorable prognosis. By immunohistochemistry we showed that the majority of tumor cells, including epidermoid, intermediate and mucous producing cells, expressed the CRTC1-MAML2 fusion protein. In contrast, 15 non MEC lacrimal neoplasm were fusion-negative. Our findings show that lacrimal MEC is not only clinically and morphologically but also genetically identical to MECs originating from other exocrine glands, including those of the lung, thyroid, cervix and salivary glands. Taken together, the present and previous studies further emphasize the fundamental biologic and genetic similarities among MECs developing from different anatomical sites and organs. Moreover, our findings indicate that the CRTC1-MAML2 fusion may be a useful diagnostic and prognostic biomarker for lacrimal MEC. PMID- 22323115 TI - Transient receptor potential melastatin-related 7 channel is overexpressed in human pancreatic ductal adenocarcinomas and regulates human pancreatic cancer cell migration. AB - Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive forms of cancer with a tendency to invade surrounding healthy tissues, leading to a largely incurable disease. Despite many advances in modern medicine, there is still a lack of early biomarkers as well as efficient therapeutical strategies. The melastatin-related transient receptor potential 7 channel (TRPM7) is a nonselective cation channel that is involved in maintaining Ca(2+) and Mg(2+) homeostasis. It has been recently reported to regulate cell differentiation, proliferation and migration. However, the role of TRPM7 in PDAC progression is far to be understood. In our study, we show that TRPM7 is 13-fold overexpressed in cancer tissues compared to the healthy ones. Furthermore, TRPM7 staining is stronger in tumors with high grade, suggesting a correlation between TRPM7 expression and PDAC progression. Importantly, TRPM7 expression is inversely related to patient survival. In BxPC-3 cell line, dialyzing the cytoplasm during the patch-clamp whole-cell recording with a 0-Mg(2+) solution activated a nonselective current with a strong outward rectification. This cation current is inhibited by intracellular Mg(2+) and by TRPM7 silencing. The downregulation of TRPM7 by small interference RNA dramatically inhibited intracellular Mg(2+) fluorescence and cell migration without affecting cell proliferation, suggesting that TRPM7 contributes to Mg(2+) entry and cell migration. Moreover, external Mg(2+) following TRPM7 silencing fully restored the cell migration. In summary, our results indicate that TRPM7 is involved in the BxPC-3 cell migration via a Mg(2+)-dependent mechanism and may be a potential biomarker of poor prognosis of PDAC. PMID- 22323116 TI - Nasopharyngeal carcinoma. PMID- 22323117 TI - Genetic characterization of H5N1 influenza viruses isolated from chickens in Indonesia in 2010. AB - Since 2003, highly pathogenic H5N1 avian influenza viruses have caused outbreaks among poultry in Indonesia every year, producing the highest number of human victims worldwide. However, little is known about the H5N1 influenza viruses that have been circulating there in recent years. We therefore conducted surveillance studies and isolated eight H5N1 viruses from chickens. Phylogenic analysis of their hemagglutinin and neuraminidase genes revealed that all eight viruses belonged to clade 2.1.3. However, on the basis of nucleotide differences, these viruses could be divided into two groups. Other viruses genetically closely related to these two groups of viruses were all Indonesian isolates, suggesting that these new isolates have been evolving within Indonesia. Among these viruses, two distinct viruses circulated in the Kalimantan islands during the same season in 2010. Our data reveal the continued evolution of H5N1 viruses in Indonesia. PMID- 22323118 TI - Concordance among physical educators', teachers', and parents' perceptions of attention problems in children. AB - OBJECTIVE: The study examined the concordance among rating sources on attention problems of elementary school-aged children. METHOD: A randomly selected sample (N = 841) of children was rated by the physical educators, the teachers, and the parents, using the Attention Scales of the Motor Behavior Checklist (MBC), the Teacher Report Form, the Child Behavior Checklist, and the ADHD-Rating Scale-IV (ADHD-RS-IV ). RESULTS: Convergent validity of the Lack of Attention Scale of the MBC with the corresponding subscales was supported. Correlations were higher between teachers' ratings and between physical educators' and teachers' ratings than between physical educators' and parents' ratings or between teachers' and parents' ratings. CONCLUSION: Findings underscore the importance of taking the child's settings and observer influences into account and suggest that MBC is a new promising instrument for screening attention problems in school settings. PMID- 22323119 TI - Working memory in ADHD: a comparison of British and South African children. AB - OBJECTIVE: The aim of the present study was to investigate the following issues: (a) Do students with ADHD have a pervasive pattern of impaired working memory skills across verbal and visuospatial domains? (b) is there evidence for a similar pattern of deficits across U.K. and South African students? and (c) which working memory tasks can effectively identify students with ADHD from TD peers? METHOD: Four groups of children participated in the study: students with ADHD and TD from the United Kingdom and students with ADHD and TD from South Africa. RESULTS: There were several key findings. First, the students with ADHD in South Africa performed significantly worse than the other groups (ADHD-United Kingdom, TD-United Kingdom, and TD-South Africa) in verbal and visuospatial short-term memory measures. Next, students with ADHD in the United Kingdom and South Africa exhibited working memory deficits extended to the visuospatial domain. This pattern was consistent with previous research in developmental populations (Alloway et al., 2006) and in adult samples (Kane et al., 2004; Park et al., 2002). A related finding was that the memory deficits in the students with ADHD (in the United Kingdom and South Africa) were significantly worse than their TD counterparts even when IQ and age were statistically accounted. These persistent deficits fit well accumulating evidence of the importance of working memory in learning. CONCLUSION: Practical implications for education will be discussed in the context of appropriate diagnosis and support in the classroom. PMID- 22323120 TI - Working memory and response inhibition as one integral phenotype of adult ADHD? A behavioral and imaging correlational investigation. AB - OBJECTIVE: It is an open question whether working memory (WM) and response inhibition (RI) constitute one integral phenotype in attention deficit hyperactivity disorder (ADHD). METHOD: The authors investigated 45 adult ADHD patients and 41 controls comparable for age, gender, intelligence, and education during a letter n-back and a stop-signal task, and measured prefrontal oxygenation by means of functional near-infrared spectroscopy. RESULTS: The authors replicated behavioral and cortical activation deficits in patients compared with controls for both tasks and also for performance in both control conditions. In the patient group, 2-back performance was correlated with stop signal reaction time. This correlation did not seem to be specific for WM and RI as 1-back performance was correlated with go reaction time. No significant correlations of prefrontal oxygenation between WM and RI were found. CONCLUSION: The authors' findings do not support the hypothesis of WM and RI representing one integral phenotype of ADHD mediated by the prefrontal cortex. PMID- 22323121 TI - ADHD Preschoolers with and without ODD: do they act differently depending on degree of task engagement/reward? AB - OBJECTIVE: To examine the impact of reinforcement on reaction time (RT) and RT variability (RT standard deviation [RTSD]) in preschoolers with ADHD with and without oppositional defiant disorder (ODD), and a typically developing (TD) comparison group. METHOD: Participants were administered a computerized task consisting of two conditions: simple RT (SRT) and reinforced SRT (SRTr). Data were analyzed using two-way (Group * Condition) mixed ANOVAs and followed-up using pairwise comparisons. RESULTS: RTs were significantly shorter and less variable during the SRTr than the SRT condition. A significant Group x Condition interaction was observed for RTSD (F= 3.38, p < .05); post hoc analyses indicated that the RTSD of the ADHD + ODD group was significantly more variable than that of the TD group during the SRT condition (F = 4.81, p < .05). However, their RTSD was statistically indistinguishable from the other groups during the SRTr condition. CONCLUSION: Preschoolers who are oppositional/defiant and hyperactive are the most responsive to feedback/reward. PMID- 22323122 TI - The earliest reference to ADHD in the medical literature? Melchior Adam Weikard's description in 1775 of "attention deficit" (Mangel der Aufmerksamkeit, Attentio Volubilis). AB - OBJECTIVE: The present article reports on the discovery and translation of a chapter in a 1775 medical textbook by the German physician, Melchior Adam Weikard, which describes attention disorders. This article is believed to be the earliest reference to the syndrome that today is known as attention deficit hyperactivity disorder, or ADHD. METHOD: The authors briefly discuss previous efforts to identify the earliest description of ADHD thought to be the lectures of George Still in 1902 and subsequently, the medical textbook by the physician, Alexander Crichton, in 1798. Background is provided on Weikard followed by the English translation of his short chapter on attention deficits and the rationale for why it should be viewed as relevant to the history of ADHD. RESULTS AND CONCLUSIONS: The authors argue that Weikard's description in 1775 now deserves to be credited with providing the first description of attention disorders in the medical literature known to date. PMID- 22323123 TI - Assessment of biliary clearance in early drug discovery using sandwich-cultured hepatocyte model. AB - It is challenging to predict biliary clearance (CL(b) ) for new chemical entities (NCEs) in early drug discovery. Although sandwich-cultured hepatocyte (SCH) model has offered a valuable tool for characterizing hepatobiliary disposition and drug drug interaction potential of NCEs, no comprehensive study was reported to project in vivo biliary clearance (in vivo CL(b,observed) ) potential using in vitro SCH model during the drug discovery stage. In this study, the CL(b) of 110 discovery compounds was evaluated using rat SCH model. Parallel artificial membrane permeability assay, Caco-2, and rat liver microsomes were employed in parallel to explore the interplay of biliary excretion with cellular permeability and liver metabolism. Selected compounds were further tested in bile-duct cannulated rats, confirming the value of the SCH model for ranking and predicting in vivo CL(b,observed) during drug discovery. For compounds with extremely low passive permeability and metabolism, rat SCH may underestimate in vivo CL(b,observed) . The combination of passive permeability, metabolic intrinsic clearance, and the SCH model could serve as an initial screening platform for biliary excretion potential as well as a means for improving compound liabilities and properties. A preliminary evaluation strategy was proposed to highlight biliary excretion risk evaluation during the drug discovery process. PMID- 22323124 TI - Practitioner and client explanations for disparities in health care use between migrant and non-migrant groups in Sweden: a qualitative study. AB - To investigate variations in explanations given for disparities in health care use between migrant and non-migrant groups, by clients and care providers in Sweden. Qualitative evidence collected during in-depth interviews with five 'migrant' health service clients and five physicians. The interview data generated three categories which were perceived by respondents to produce ethnic differences in health service use: "Communication issues", "Cultural differences in approaches to medical consultations" and "Effects of perceptions of inequalities in care quality and discrimination". Explanations for disparities in health care use in Sweden can be categorized into those reflecting social/structural conditions and the presence/absence of power and those using cultural/behavioural explanations. The negative perceptions of 'migrant' clients held by some Swedish physicians place the onus for addressing their poor health with the clients themselves and risks perpetuating their health disadvantage. The power disparity between doctors and 'migrant' patients encourages a sense of powerlessness and mistreatment among patients. PMID- 22323125 TI - Benzofurans from benzophenones and dimethylacetamide: copper-promoted cascade formation of furan O1-C2 and C2-C3 bonds under oxidative conditions. PMID- 22323126 TI - Glucagon-like peptide-2 increases dysplasia in rodent models of colon cancer. AB - The intestinal hormone, glucagon-like peptide-2 (GLP-2), enhances intestinal growth and reduces inflammation in rodent models. Hence, a degradation-resistant GLP-2 analog is under investigation for treatment of Crohn's disease. However, GLP-2 increases colonic dysplasia in murine azoxymethane (AOM)-induced colon cancer. Considering the increased colon cancer risk associated with chronic colitis, we have therefore examined the effects of long-acting hGly(2)GLP-2, as well as of endogenous GLP-2 using the antagonist hGLP-2(3-33) in two novel models of inflammation-associated colon cancer: rats fed the carcinogen 2-Amino-1-methyl 6-phenylimidazo[4,5-b]pyridine (PhIP) and a high-fat diet (HFD) for one or three cycles, and mice with chronic dextran sodium-sulfate (DSS)-induced colitis administered AOM. hGly(2)GLP-2 treatment of one-cycle PhIP/HFD rats increased the number of colonic aberrant crypt foci by 72 +/- 11% (P < 0.01). Fifty-one weeks after three PhIP/HFD cycles, hGly(2)GLP-2-treated rats had a 22% incidence of colon cancer, compared with 0% in vehicle-treated rats. AOM-DSS mice treated with vehicle or hGly(2)GLP-2 had high-grade dysplasia/colon cancer incidences of 56 and 64%, respectively, compared with 46% in hGLP-2(3-33)-treated AOM-DSS animals (P < 0.05). Unexpectedly, hGLP-2(3-33) also reduced the colitis damage score by 32.0 +/- 8.4% (P < 0.05). All high-grade dysplastic/cancerous tumors had nuclear localization of beta-catenin although beta-catenin mRNA transcript and protein levels did not differ between treatment groups. GLP-2 receptor mRNA expression also was not different. However, hGLP-2(3-33)-treated mice had markedly reduced numbers of doublecortin-and-calmodulin-kinase-like-1-positive stem cells, by 73.7 +/- 8.6% (P < 0.05). In conclusion, the results of this study indicate a role for hGly(2)GLP-2 and endogenous GLP-2 as potential cancer promoters in rodents. PMID- 22323128 TI - Upper esophageal sphincter impedance as a marker of sphincter opening diameter. AB - The measurement of the physical extent of opening of the upper esophageal sphincter (UES) during bolus swallowing has to date relied on videofluoroscopy. Theoretically luminal impedance measured during bolus flow should be influenced by luminal diameter. In this study, we measured the UES nadir impedance (lowest value of impedance) during bolus swallowing and assessed it as a potential correlate of UES diameter that can be determined nonradiologically. In 40 patients with dysphagia, bolus swallowing of liquids, semisolids, and solids was recorded with manometry, impedance, and videofluoroscopy. During swallows, the UES opening diameter (in the lateral fluoroscopic view) was measured and compared with automated impedance manometry (AIM)-derived swallow function variables and UES nadir impedance as well as high-resolution manometry-derived UES relaxation pressure variables. Of all measured variables, UES nadir impedance was the most strongly correlated with UES opening diameter. Narrower diameter correlated with higher impedance (r = -0.478, P < 0.001). Patients with <10 mm, 10-14 mm (normal), and >= 15 mm UES diameter had average UES nadir impedances of 498 +/- 39 Ohms, 369 +/- 31 Ohms, and 293 +/- 17 Ohms, respectively (ANOVA P = 0.005). A higher swallow risk index, indicative of poor pharyngeal swallow function, was associated with narrower UES diameter and higher UES nadir impedance during swallowing. In contrast, UES relaxation pressure variables were not significantly altered in relation to UES diameter. We concluded that the UES nadir impedance correlates with opening diameter of the UES during bolus flow. This variable, when combined with other pharyngeal AIM analysis variables, may allow characterization of the pathophysiology of swallowing dysfunction. PMID- 22323127 TI - Pharmacological and genetic inhibition of calcineurin protects against carbachol induced pathological zymogen activation and acinar cell injury. AB - Acute pancreatitis is a major health burden for which there are currently no targeted therapies. Premature activation of digestive proenzymes, or zymogens, within the pancreatic acinar cell is an early and critical event in this disease. A high-amplitude, sustained rise in acinar cell Ca(2+) is required for zymogen activation. We previously showed in a cholecystokinin-induced pancreatitis model that a potential target of this aberrant Ca(2+) signaling is the Ca(2+)-activated phosphatase calcineurin (Cn). However, in this study, we examined the role of Cn on both zymogen activation and injury, in the clinically relevant condition of neurogenic stimulation (by giving the acetylcholine analog carbachol) using three different Cn inhibitors or Cn-deficient acinar cells. In freshly isolated mouse acinar cells, pretreatment with FK506, calcineurin inhibitory peptide (CiP), or cyclosporine (CsA) blocked intra-acinar zymogen activation (n = 3; P < 0.05). The Cn inhibitors also reduced leakage of lactate dehydrogenase (LDH) by 79%, 62%, and 63%, respectively (n = 3; P < 0.05). Of the various Cn isoforms, the beta isoform of the catalytic A subunit (CnAbeta) was strongly expressed in mouse acinar cells. For this reason, we obtained acinar cells from CnAbeta-deficient mice (CnAbeta-/-) and observed an 84% and 50% reduction in trypsin and chymotrypsin activation, respectively, compared with wild-type controls (n = 3; P < 0.05). LDH release in the CnAbeta-deficient cells was reduced by 50% (n = 2; P < 0.05). The CnAbeta-deficient cells were also protected against zymogen activation and cell injury induced by the cholecystokinin analog caerulein. Importantly, amylase secretion was generally not affected by either the Cn inhibitors or Cn deficiency. These data provide both pharmacological and genetic evidence that implicates Cn in intra-acinar zymogen activation and cell injury during pancreatitis. PMID- 22323129 TI - Protective role of adiponectin against ethanol-induced gastric injury in mice. AB - Adiponectin is an anti-inflammatory molecule released from adipocytes, and serum adiponectin concentrations are reduced in obesity. We previously reported that gastric erosion occurs in association with obesity and low serum adiponectin levels. In the present study, we examined adiponectin-knockout (APN-KO) mice to elucidate the role of adiponectin in gastric mucosal injury. Gastric injury was induced by oral administration of ethanol in wild-type (WT) and APN-KO mice. Ethanol treatment induced severe gastric injury in APN-KO mice compared with WT mice. In APN-KO mice, increased apoptotic cells and decreased expression of prostaglandin E(2) (PGE(2)) were detected in the injured stomach. We next assessed the effect of adiponectin on the cellular response to ethanol treatment and wound repair in rat gastric mucosal cells (RGM1). Adiponectin induced the expression of PGE(2) and cyclooxygenase 2 (COX-2) in ethanol-treated RGM1 cells. RGM1 cells exhibited efficient wound repair accompanied by increased PGE(2) expression in the presence of adiponectin. Coadministration of adiponectin with celecoxib, a COX-2 inhibitor, inhibited efficient wound repair. These findings indicate that adiponectin has a protective role against ethanol-induced gastric mucosal injury in mice. This effect may be partially mediated by the efficient wound repair of epithelial cells via increased PGE(2) expression. PMID- 22323130 TI - Resistance to paclitaxel in hepatoma cells is related to static JNK activation and prohibition into entry of mitosis. AB - Hepatocellular carcinoma (HCC) generally shows chemoresistant features to anticancer agents. Paclitaxel has been clinically used in the treatment of various cancers. However, effect of paclitaxel on HCC has not been adequately addressed. Here, we found two categories of hepatoma cells in response to paclitaxel. Paclitaxel effectively decreased the cell viability of SNU475, Hep3B, and SNU387 HCC cells and Chang liver cells (death prone). In contrast, the other five hepatoma cell lines (SNU449, SNU398, SUN368, SNU354, and HepG2 cells) were resistant to paclitaxel (death reluctant). In response to paclitaxel, Bcl-2 was highly phosphorylated in death-prone cells, whereas much less Bcl-2 was phosphorylated in death-reluctant cells. Cotreatment with SP600125, an inhibitor JNK, significantly reduced the phosphorylated Bcl-2 in death-prone cells and caused a significant reduction in cell death. The reduced cell death was due to prohibition into mitotic entry as evidenced by low cyclin B(1)/Cdk1 kinase activity. In death-reluctant cells, inbuild-phospho-JNK levels were high but no longer activated in response to paclitaxel. We found that paclitaxel combined with caffeine or UCN-01, inhibitors of G(2) DNA damage checkpoint, was able to partially overcome resistance to paclitaxel in these cells. Thus our data provide the molecular basis of paclitaxel resistance in hepatoma cells, and appropriate combination therapy may increase treatment efficacy. PMID- 22323131 TI - SERT and TPH-1 mRNA expression are reduced in irritable bowel syndrome patients regardless of visceral sensitivity state in large intestine. AB - Colorectal visceral hypersensitivity has been demonstrated in a subset of irritable bowel syndrome (IBS) patients. Serine protease and serotonergic signaling modulate gastrointestinal visceral sensitivity. We evaluated whether altered mucosal serine protease and serotonergic pathway components are related to rectal visceral hypersensitivity in IBS patients. Colorectal mucosal biopsies of 23 IBS patients and 15 controls were collected. Gene transcripts of protease activated receptor (PAR)-2, trypsinogen IV, tryptophan hydroxylase (TPH)-1, and serotonin reuptake transporter (SERT) were quantified using real-time polymerase chain reaction. Substance P and 5-HT contents were measured by ELISA. The number of enterochromaffin cells, mast cells, and intraepithelial lymphocytes was determined using immunohistochemistry. Rectal visceral sensitivity was determined in IBS patients using barostat programmed for phasic ascending distension. Rectal hypersensitivity (+) and (-) IBS patients showed lower TPH-1 and SERT mRNA levels in the rectum compared with controls (P <= 0.05). Rectal hypersensitivity (+) IBS patients (n = 12) showed lower TPH-1 mRNA level in the sigmoid compared with controls (P = 0.015). No significant differences were observed in PAR-2 and trypsinogen IV expression between controls and IBS patients. Rectal substance P content was increased in IBS patients compared with controls (P = 0.045). No significant differences were found in transcript levels, cell counts, and substance P and 5-HT contents between rectal hypersensitivity (+) and (-) IBS patients. In conclusion, regardless of visceral hypersensitivity state, several serotonergic signaling components are altered in IBS patients. PMID- 22323132 TI - Pectus excavatum (funnel chest): a historical and current prospective. AB - Pectus excavatum (PE) is a relatively common deformity involving the anterior chest wall. It is represented clinically as a conical depression of the sternum and costal cartilages with the apex at the xiphoid process. Associated features and symptoms vary but generally involve respiratory and cardiac abnormalities. Since it's initial description, numerous surgical techniques have been developed to correct PE, with the Ravtich (open) and Nuss (minimally invasive) procedures being the most commonly employed. Although the etiology remains unclear, the pathogenesis of PE is currently thought to involve the overgrowth of the costochondral region of the ribs. In addition, documented case reports of familial pectus excavatum exist, suggesting a heritable form of the defect. Numerous genetic markers have also been discovered, linking PE to various genetic syndromes. PMID- 22323133 TI - Ultrasonic microwave-assisted extraction coupled with high-speed counter-current chromatography for the preparation of nigakinones from Picrasma quassioides (D.Don) Benn. AB - INTRODUCTION: Nigakinones are the main effective compounds of Picrasma quassioides (D. Don) Benn and are widely used in traditional Chinese medicine, therefore a rapid and efficient separation and purification method is necessary. OBJECTIVE: To develop a new method based on ultrasonic microwave-assisted extraction (UMAE) and high-speed counter-current chromatography (HSCCC) for the rapid separation and purification of nigakinone and methylnigakinone from P. quassioides (D.Don) Benn. METHODOLOGY: Response surface methodology (RSM) was used to optimise the extraction conditions of UMAE: 10.0 g of original sample was extracted with 210 mL of 90% (v/v) aqueous methanol at 60 degrees C for 13 min, ultrasonic power was 100 W and microwave power was dynamically adjusted to the given temperature. After extraction, the extract was introduced into the HSCCC and separated with a hexane:ethyl acetate:methanol:2% acetic acid (9:11:9:11, v/v/v/v) solvent system. RESULTS: About 2.1 mg nigakinone with purity of 96.8% was obtained in one step within 200 min, methylnigakinone was also obtained with a purity of 75.6%. Their chemical structures were identified with ESI-MS and 1H NMR. CONCLUSION: UMAE coupled with HSCCC was found to be a promising and feasible alternative method to separate and purify alkaloids from natural herbs such as P. quassiodes. PMID- 22323134 TI - Modulating self-assembly of amyloidogenic proteins as a therapeutic approach for neurodegenerative diseases: strategies and mechanisms. AB - Abnormal protein assembly causes multiple devastating disorders in the central nervous system (CNS), such as Alzheimer's, Parkinson's, Huntington's, and prion diseases. Due to the now extended human lifespan, these diseases have been increasing in prevalence, resulting in major public health problems and the associated financial difficulties worldwide. The wayward proteins that lead to disease self-associate into neurotoxic oligomers and go on to form fibrillar polymers through multiple pathways. Thus, a range of possible targets for pharmacotherapeutic intervention exists along these pathways. Many compounds have shown different levels of effectiveness in inhibiting aberrant self-assembly, dissociating existing aggregates, protecting cells against neurotoxic insults, and in some cases ameliorating disease symptoms in vivo, yet achieving efficient, disease-modifying therapy in humans remains a major unattained goal. To a large degree, this is because the mechanisms of action for these drugs are essentially unknown. For successful design of new effective drugs, it is crucial to elucidate the mechanistic details of their action, including the actual target(s) along the protein aggregation pathways, how the compounds modulate these pathways, and their effect at the cellular, tissue, organ, and organism level. Here, the current knowledge of major mechanisms by which some of the more extensively explored drug candidates work are discussed. In particular, we focus on three prominent strategies: 1) stabilizing the native fold of amyloidogenic proteins, 2) accelerating the aggregation pathways towards the fibrillar endpoint thereby reducing accumulation of toxic oligomers, and 3) modulating the assembly process towards nontoxic oligomers/aggregates. The merit of each strategy is assessed, and the key points to consider when analyzing the efficacy of possible drug candidates and their mechanism of action are discussed. PMID- 22323135 TI - Introduction: why analyze single cells? AB - Powerful methods in molecular biology are abundant; however, in many fields including hematology, stem cell biology, tissue engineering, and cancer biology, data from tools and assays that analyze the average signals from many cells may not yield the desired result because the cells of interest may be in the minority their behavior masked by the majority-or because the dynamics of the populations of interest are offset in time. Accurate characterization of samples with high cellular heterogeneity may only be achieved by analyzing single cells. In this chapter, we discuss the rationale for performing analyses on individual cells in more depth, cover the fields of study in which single-cell behavior is yielding new insights into biological and clinical questions, and speculate on how single cell analysis will be critical in the future. PMID- 22323136 TI - Flow cytometry and microscopy as means of studying single cells: a short introductional overview. AB - Flow cytometry and microscopy are perhaps the two most commonly used techniques for analyzing single cells. Both techniques are typically robust and provide a high throughput analysis of living and/or fixed cells. The techniques are often combined with fluorescent labeling of cells, using for example antibodies. This chapter is a short introductory review where some of the possible applications using flow cytometry and microscopy are discussed. PMID- 22323137 TI - Identification of enzyme-converted peptide products from single cells using capillary electrophoresis and liquid chromatography-mass spectrometry. AB - Single-cell analysis using chemical methods, otherwise known as chemical cytometry, promises to provide significant leaps in understanding signaling processes which result in cellular behavior. Sensitive methods for chemical cytometry such as capillary electrophoresis can detect and quantify multiple targets; however, conclusive identification of detected analytes is required for useful data to be obtained. Here, we demonstrate a method for determining the identity of enzyme-converted peptide products from single cells using a combination of capillary electrophoresis and liquid chromatography-mass spectrometry (LC-MS). PMID- 22323138 TI - Laser capture microdissection for gene expression analysis of specific cell populations in single blastocysts. AB - Laser capture microdissection (LCM) allows for the isolation of small tissue fractions from heterogeneous tissue sections, for downstream genetic or proteomic analysis without contamination by the surrounding tissue. This technique can also be successfully used for the isolation of small tissue fractions from developing embryos, such as expanding blastocysts. However, the small size of early-stage embryos hampers tissue processing prior to LCM. The present protocol describes the application of LCM to isolate specific cell fractions from blastocysts for downstream gene expression analysis with RT-PCR. PMID- 22323139 TI - Single-cell culture in microwells. AB - In order to better understand cellular processes and behavior, a controlled way of studying high numbers of single cells and their clone formation is greatly needed. This chapter describes a microwell plate with 672 wells in a standard array/slide format, applied for single-cell culture and analysis. Single cells can be seeded into each well of the plate (1) manually or (2) automatically using a sorting flow cytometer, followed by week-long culture and detection of cell growth, protein expression, etc. The glass/silicon plate is compatible with most standard instrumentation to facilitate easy handling and enable use of the plate for single-cell analysis in most laboratory settings. PMID- 22323140 TI - Isodielectric separation and analysis of cells. AB - Measuring the electrical properties of a cell provides a fast and accessible means of identifying or characterizing cells whose biological state differs from the population as a whole. This chapter describes a microfluidic method for characterizing the electrical properties of cells based upon their convergence to equilibrium in an electrical conductivity gradient. The method, called isodielectric separation, uses the dielectrophoretic force induced on polarizable objects in spatially nonuniform electric fields to deflect cells to the point in the conductivity gradient where their polarization charge vanishes. This equilibrium position encodes the cell's electrical properties and can be used to identify cells that are electrically distinct from a background population, to determine the extent of this difference, and to physically isolate them for further study. PMID- 22323141 TI - Single cell electroporation using microfluidic devices. AB - Electroporation is a powerful technique to increase the permeability of cell membranes and subsequently introduce foreign materials into cells. Pores are created in the cell membrane upon application of an electric field (kV/cm). Most applications employ bulk electroporation, at the scale of 1 mL of cells (ca. one million cells). However, recent progresses have shown the interest to miniaturize the technique to a single cell. Single cell electroporation is achieved either using microelectrodes which are placed in close vicinity to one cell, or in a microfluidic format. We focus here on this second approach, where individual cells are trapped in micrometer-size structures within a microchip, exposed in situ to a high electric field and loaded with either a dye (proof-of-principle experiments) or a plasmid. Specifically, we present one device that includes an array of independent electroporation sites for customized and successive poration of nine cells. The different steps of the single cell electroporation protocol are detailed including cell sample preparation, cell trapping, actual cell poration and on-chip detection of pore formation. Electroporation is illustrated here with the transport of dyes through the plasma membrane, the transfection of cells with GFP-encoding plasmids, and the study of the ERK1 signaling pathway using a GFP-ERK1 protein construct expressed by the cells after their transfection with the corresponding plasmid. This last example highlights the power of microfluidics with the implementation of various steps of a process (cell poration, culture, imaging) performed at the single cell level, on a single device. PMID- 22323142 TI - Perfusion culture of mammalian cells in a microfluidic channel with a built-in pillar array. AB - In vitro culture of mammalian cells is fundamental to various biological studies such as single cell analysis, pathological research, and drug/therapy development. However, there are limitations with the current in vitro cell culture methods. Cells tend to lose their specific functions due to the lack of a cellular microenvironment when they are maintained under standard culture conditions. Microscale devices can be a novel tool to reestablish a cellular microenvironment for culturing mammalian cells in vitro and maintaining their differentiated functions. Different microscale cell culture techniques have been developed to suit different biological applications. This chapter describes a method to trap and culture mammalian cells in a microfluidic channel with a built in pillar array. PMID- 22323143 TI - Padlock probes and rolling circle amplification for detection of repeats and single-copy genes in the single-cell comet assay. AB - Padlock probes and rolling circle amplification are techniques which can be used for detection of DNA sequences in situ with high specificity and high signal to noise. The single-cell gel electrophoresis assay is used to measure DNA damage and repair in cells. Here, we describe how padlock probes and rolling circle amplification can be used to detect DNA sequences within comet preparations. PMID- 22323144 TI - Droplet microfluidics for single-cell analysis. AB - This book chapter aims at providing an overview of all the aspects and procedures needed to develop a droplet-based workflow for single-cell analysis (see Fig. 10.1). The surfactant system used to stabilize droplets is a critical component of droplet microfluidics; its properties define the type of droplet-based assays and workflows that can be developed. The scope of this book chapter is limited to fluorinated surfactant systems that have proved to generate extremely stable droplets and allow to easily retrieve the encapsulated material. The formulation section discusses how the experimental parameters influence the choice of the surfactant system to use. The circuit design section presents recipes to design and integrate different droplet modules into a whole assay. The fabrication section describes the manufacturing of microfluidic chip including the surface treatment which is pivotal in droplet microfluidics. Finally, the last section reviews the experimental setup for fluorescence detection with an emphasis on cell injection and incubation. PMID- 22323145 TI - Screening of antigen-specific antibody-secreting cells. AB - Screening of antigen-specific antibody-producing cells is a key step for obtaining antigen-specific monoclonal antibodies. In murine system, hybridoma between B-lymphocytes and myeloma cells is used to screen and produce antigen specific monoclonal antibodies. In human system, good hybridoma-producing system is not available. Instead, transformation of B-lymphocytes with Epstein-Barr viruses is used to obtain antibody-secreting cell lines. Furthermore, phage display system using molecular biology is recently used to obtain antigen specific human monoclonal antibodies. Here, we describe the new method for screening antigen-specific antibody-secreting cells at single-cell levels using microwell-array chips. The system can be applied to screen antigen-specific antibody-secreting cells from any animal species. PMID- 22323146 TI - Analysis of single eukaryotic cells using Raman Tweezers. AB - Raman Tweezers is a technique that combines optical trapping with Raman spectroscopy and has enabled the spectroscopic analysis of single cells. Applications of this technique include the identification and discrimination of different types of cells, including healthy and non-healthy cells (e.g. cancer cells). In addition, the interaction of cells with stimuli, e.g. drugs, can also be studied on a single-cell basis. Herein, a generic protocol for the analysis of fixed and living single eukaryotic cells is described, including the considerations required to build a Raman Tweezers systems. PMID- 22323147 TI - Single-cell microinjection technologies. AB - Single-cell microinjection, as a mechanical delivery tool, has been used for transferring substances into transfection or infection challenging cells. Here, we discuss the advantages and applications of microinjection, list the materials needed for performing microinjection experiments, and describe the methods of single-cell microinjection into suspended and attached cells. PMID- 22323148 TI - Ultrasonic manipulation of single cells. AB - Ultrasonic manipulation has emerged as a simple and powerful tool for trapping, aggregation, and separation of cells. During the last decade, an increasing amount of applications in the microscale format has been demonstrated, of which the most important is acoustophoresis (continuous acoustic cell or particle separation). Traditionally, the technology has proven to be suitable for treatment of high-density cell and particle suspensions, where large cell and particle numbers are handled simultaneously. In this chapter, we describe how ultrasound can be combined with microfluidics and microplates for particle and cell manipulation approaching the single-cell level. We demonstrate different cell handling methods with the purpose to select, trap, aggregate, and position individual cells in microdevices based on multifrequency ultrasonic actuation, and we discuss applications of the technology involving immune cell interaction studies. PMID- 22323149 TI - Expanding the horizons for single-cell applications on lab-on-a-chip devices. AB - Stochastic events in gene expression, protein synthesis, and metabolite synthesis or degradation lead to cellular heterogeneity essential to life. In a tissue as we see in organs, there is strong heterogeneity among the constituting cells critical to its function. Thus, there exists a strong demand to develop new micro/nanosystems that would enable us to conduct single-cell analysis. This field is rapidly growing, as exemplified below with recent emerging technologies that now reveal sensitive single-cell "omics" analysis. We describe in the review some of the most promising technologies that will certainly transform our view of biology in the near future. PMID- 22323150 TI - Analytical technologies for integrated single-cell analysis of human immune responses. AB - The immune system is a network of cells in which the constitutive members interact through dense and sometimes overlapping connections. The extreme complexity of this network poses a significant challenge for monitoring pathological conditions (e.g., food allergies, autoimmunity, and other chronic inflammatory diseases) and for discovering robust signatures of immunological responses that correlate with or predict the efficacy of interventions. The diversity among immune cells found in clinical samples (variations in cellular functions, lineages, and clonotypic breadth) requires approaches for monitoring immune responses with single-cell resolution.In this chapter, we present an engineering approach for integrated single-cell analysis that uses interchangeable modular operations to provide a comprehensive characterization of the phenotypic, functional, and genetic variations for individual cells. We focus on the use of microfabricated devices to isolate and interrogate single cells, and on the analytical components that enable subsequent detection, correlation, and interpretation of multidimensional sets of data. We discuss specific challenges and opportunities in the realization of this concept, and review two examples where it has been implemented. The presented approach should provide a basis for the design and implementation of nonconventional bioanalytical processes for studying specific responses of an immune system. PMID- 22323151 TI - Depressive symptoms and apathy are associated with psychomotor slowness and frontal activation. AB - Affective symptoms, such as depression and apathy, and cognitive dysfunction, such as psychomotor slowness, are known to have negative impacts on the quality of life (QOL) of patients with mental and physical diseases. However, the relationships among depressive symptoms, apathy, psychomotor slowness, and QOL in a non-clinical population are unclear. The aim of the present study was to assess these relationships and examine the underlying cortical mechanisms in a non clinical population. Fifty-two healthy male volunteers were assessed for depressive symptoms using the Zung Self-rating Depression Scale (SDS), for apathy measured using the Apathy Scale, and QOL using the Short-Form 36 item questionnaire (SF36). The volunteers also performed the Trail Making Test Part A (TMT-A) while undergoing assessment of hemoglobin concentration changes in the frontal cortical surface using 24-channel near-infrared spectroscopy (NIRS). The scores of the SDS and Apathy Scale showed significant negative correlations with the scores of most of subscales of the SF36. In addition, the SDS score had a significant positive correlation with the time to complete the TMT-A. Further, activation of several frontal cortical areas had a significant positive correlation with the scores of the SDS and Apathy Scale. These results suggest that the degree of depressive symptoms and apathy are associated with a lower QOL in a non-clinical population and that cortical hyperactivation during a psychomotor task measured by NIRS may identify objectively individuals with a high degree of depressive symptoms and apathy. PMID- 22323152 TI - Nuclear accumulation of seven in absentia homologue-2 supports motility and proliferation of liver cancer cells. AB - Stability of many tumor-relevant proteins is partly mediated by E3 ligases, which determine substrate specificity within the ubiquitin system. Recent data demonstrated that increased nuclear expression of the E3 ligase seven in absentia homologue (SIAH)-1 in human hepatocarcinogenesis supports tumor cell proliferation and migration. To define whether closely related SIAH-2 synergizes with protumorigenic SIAH-1, we systematically analyzed expression, localization and functional relevance of SIAH-2 in human hepatocellular carcinoma (HCC). Nuclear accumulation of SIAH-2 is detectable in more than 60% of all HCCs and correlates with tumor progression, cell proliferation and distant metastasis. An inverse correlation between nuclear SIAH-1 and SIAH-2 was detected, suggesting independent mechanisms for nuclear enrichment. Inhibition of nuclear SIAH-2 by RNAi in HCC cell lines reduced proliferation as well as lateral tumor cell motility and transmigration; however, combined knock down of both SIAH-1 and SIAH 2 did not further amplify biological effects compared to single gene inhibition. Reduction of SIAH-2 expression sensitizes HCC cells to the treatment with different cytostatic drugs, demonstrating that SIAH-2-targeting approaches may increase the response of HCC cells to conventional chemotherapy. Together, these data show that SIAH-2--as described for SIAH-1--accumulates in nuclei of HCC cells where it supports tumor growth and tumor cell dissemination. Because the nuclear pattern of SIAH-2 differs in HCC tissues from the SIAH-1 pattern and because the inactivation of SIAH-2 is not compensated by SIAH-1, the specific inhibition of SIAH-2 (especially in combination with other drugs) represents a promising therapeutic strategy for HCC. PMID- 22323153 TI - No small matter setting up small business exchanges. PMID- 22323154 TI - Deepening drug shortages. PMID- 22323155 TI - Employers and the exchanges under the small business health options program: examining the potential and the pitfalls. AB - The health insurance exchange is the centerpiece of the insurance reforms created by the Affordable Care Act. The Small Business Health Options Program (SHOP) is intended to create a marketplace for small, and perhaps eventually large, employers to purchase health insurance for their employees. This paper introduces a collection of articles that illuminate the need for small-business exchanges and discuss how they will function. The paper also describes the difficulties these exchanges will face, as well as the opportunities they will offer to states, employers, and individuals. The success or failure of small-business exchanges may well hinge on how states choose to address these challenges. PMID- 22323156 TI - How small business health exchanges can offer value to their future customers- and why they must. AB - The success of the Small Business Health Options Program (SHOP)-health insurance exchanges targeted at the small-group market and opening for business in January 2014-will depend in large part on persuading small employers and qualified health plans to participate. The most important objective will be offering employers lower-cost health plans than they have now. Other critical objectives will be offering small firms administrative efficiencies and access to choices among high value plans that are not offered elsewhere. This article frames the challenges that exchanges will encounter in meeting these objectives. In particular, it discusses the advisability of small-business exchanges' offering an "employee choice" model (which the article describes in detail); of combining the small business and individual exchanges to broaden product offerings and gain operational efficiencies; and of encouraging low-cost plans to enter the exchange market, perhaps by enabling Medicaid managed care plans to offer comparable commercial products, and in turn affording health plans access to a uniquely motivated market of small firms and their workers who want affordable coverage. PMID- 22323157 TI - Health insurance exchanges of past and present offer examples of features that could attract small-business customers. AB - The Affordable Care Act calls on states to create health insurance exchanges serving small businesses by 2014. These exchanges will allow small-business owners to pool their buying power, have more choices of health plans, and buy affordable health insurance. However, creating an exchange that appeals to small business owners poses several challenges. Past and current exchanges provide valuable insights into the role exchanges can play, services they can offer, and design features that can make them successful. For example, states should allow insurance brokers to provide employers with advice and analysis regarding plans offered in the exchanges. Exchanges should also provide services to ease enrollment, such as a single application for all of the plans they offer, and make additional benefits, such as wellness programs, available on a stand-alone basis or within insurance plans. PMID- 22323158 TI - How choices in exchange design for states could affect insurance premiums and levels of coverage. AB - The Affordable Care Act gives states the option to create health insurance exchanges from which individuals and small employers can purchase health insurance. States have considerable flexibility in how they design and implement these exchanges. We analyze several key design options being considered, using the Urban Institute's Health Insurance Policy Simulation Model: creating separate versus merged small-group and nongroup markets, eliminating age rating in these markets, removing the small-employer credit, and setting the maximum number of employees for firms in the small-group market at 50 versus 100 workers. Among our findings are that merging the small-group and nongroup markets would result in 1.7 million more people nationwide participating in the exchanges and, because of greater affordability of nongroup coverage, approximately 1.0 million more people being insured than if the risk pools were not merged. The various options generate relatively small differences in overall coverage and cost, although some, such as reducing age rating bands, would result in higher costs for some people while lowering costs for others. These cost effects would be most apparent among people who purchase coverage without federal subsidies. On the whole, we conclude that states can make these design choices based on local support and preferences without dramatic repercussions for overall coverage and cost outcomes. PMID- 22323159 TI - Large employers see scenarios under which they could move workers and retirees to exchanges. AB - Large employers are thinking about how they might use the health insurance exchanges created by the Affordable Care Act. In the short term, from 2014 to 2016, many of these employers are giving serious consideration to using the exchanges to help provide coverage for part-time workers and for retirees not yet eligible for Medicare. In the long term, beginning in 2017, some large employers are considering using the exchanges to provide coverage for all of their employees. Costs, human resources strategies, and competitive pressures, as well as state and federal policy, will be the likely drivers of large employers' decisions about whether-and how-to use the exchanges. PMID- 22323160 TI - Adjusting for risk selection in state health insurance exchanges will be critically important and feasible, but not easy. AB - The Affordable Care Act calls for the establishment of state-level health insurance exchanges. The viability and success of these exchanges will require effective risk-adjustment strategies to compensate for differences in enrollees' health status across health plans. This article describes why the Affordable Care Act could lead to favorable or adverse risk selection across plans. It reviews provisions in the act and recent proposed regulations intended to mitigate the problem of risk selection. We performed a simulation that showed that under the premium rating restrictions in the law, large incentives for insurers to attract healthier enrollees will be likely to persist-resulting in substantial overpayment to plans with very healthy enrollees and underpayment to plans with very sick members. We conclude that risk adjustment based on patients' diagnoses, such as will be in place from 2014 on, will yield payments to insurers that will be more accurate than what will come solely from the age-adjusted and other rating allowed by the act. We also describe additional challenges of implementing risk adjustment. PMID- 22323161 TI - Regulating stop-loss coverage may be needed to deter self- insuring small employers from undermining market reforms. AB - As implementation of the Affordable Care Act reshapes the US health insurance market, state policy makers should be prepared to revisit regulation of stop-loss coverage-a form of reinsurance-for small businesses. Aspects of the reform law could motivate small businesses to self-insure, rather than participate in state regulated markets either inside or outside the new health insurance exchanges. If younger or healthier groups self-insure, premiums for insured plans might rise to an extent that could seriously impair the regulated market. States can influence small businesses to participate in the regulated market by making it more difficult or costly to obtain stop-loss coverage, which self-funded employers rely on to protect their businesses from catastrophic medical costs incurred by one or more insured workers. States can limit the comprehensiveness of stop-loss coverage, ban stop-loss coverage outright, or regulate it as they do primary coverage. But states need federal guidance about how to exercise this authority if they are to promote, or prevent the undermining of, important aspects of federal health care reform. PMID- 22323162 TI - Small firms' actions in two areas, and exchange premium and enrollment impact. AB - The Affordable Care Act changed the regulations governing small firms' health insurance premiums. However, small businesses can avoid many of the new regulations by self-insuring or maintaining grandfathered plans. If small firms with healthy and lower-cost enrollees avoid the regulations, premiums for coverage sold through insurance exchanges could be unaffordable. In this analysis we used the RAND Comprehensive Assessment of Reform Efforts microsimulation model to predict the effects of self-insurance and grandfathering exemptions on coverage and premiums available through the exchanges. We estimate that Affordable Care Act regulations restricting employers' ability to offer grandfathered plans will result in lower premiums on plans available through the exchanges and will have small negative effects on enrollment in the exchanges. Our results suggest that these regulations are essential to keeping premiums on the Small Business Health Options Program (SHOP) exchanges affordable. Our analysis also found that Affordable Care Act regulations limiting self-insurance will reduce enrollment in the exchanges somewhat, without substantially affecting exchange premiums. PMID- 22323163 TI - Colorado's health insurance exchange: how one state has so far forged a bipartisan path through the partisan wilderness. PMID- 22323164 TI - Tim Jost of Washington & Lee and the duty of health reform. PMID- 22323165 TI - Lessons for coverage expansion: a Virginia primary care program for the uninsured reduced utilization and cut costs. AB - The Affordable Care Act will expand health insurance coverage for an estimated thirty-two million uninsured Americans. Increased access to care is intended to reduce the unnecessary use of services such as emergency department visits and to achieve substantial cost savings. However, there is little evidence for such claims. To determine how the uninsured might respond once coverage becomes available, we studied uninsured low-income adults enrolled in a community-based primary care program at Virginia Commonwealth University Medical Center. For people continuously enrolled in the program, emergency department visits and inpatient admissions declined, while primary care visits increased during the study period. Inpatient costs fell each year for this group. Over three years of enrollment, average total costs per year per enrollee fell from $8,899 to $4,569- a savings of almost 50 percent. We conclude that previously uninsured people may have fewer emergency department visits and lower costs after receiving coverage but that it may take several years of coverage for substantive health care savings to occur. PMID- 22323166 TI - Two responses to a premium hike in a program for uninsured kids: 4 in 5 families stay in as enrollment shrinks by a fifth. AB - This article reports on our study of the effect of premium increases on disenrollment from a health insurance program for low-income immigrant children in Los Angeles County. Two groups of children were compared: those ages 6-18, who were subject to an increase, and those ages 0-5, who were not. Fewer than half of the children in the older group remained enrolled after the premium increase slightly more than 12,000 children, compared to more than 25,000 at the beginning and there was a 20 percent decline in overall membership in the program that was attributable to the increase. Although many families paid the higher premium to keep their children enrolled, other families were not able to do so. As programs serving disadvantaged populations contemplate premium increases, we recommend that they tailor specific interventions to children most likely to drop out; establish "hardship funds" to support children with special needs; and link families that may disenroll their children with other programs that could provide coverage or providers who could offer care. PMID- 22323167 TI - Spurring enrollment in Medicare savings programs through a substitute for the asset test focused on investment income. AB - Fewer than one-third of eligible Medicare beneficiaries enroll in Medicare savings programs, which pay premiums and, in some cases, eliminate out-of-pocket cost sharing for poor and near-poor enrollees. Many beneficiaries don't participate in savings programs because they must complete a cumbersome application process, including a burdensome asset test. We demonstrate that a streamlined alternative to the asset test-allowing seniors to qualify for Medicare savings programs by providing evidence of limited assets or showing a lack of investment income-would permit 78 percent of currently eligible seniors to bypass the asset test entirely. This simplified approach would increase the number of beneficiaries who qualify for Medicare savings programs from the current 3.6 million seniors to 4.6 million. Such an alternative would keep benefits targeted to people with low assets, eliminate costly administrative expenses and obstacles to enrollment associated with the asset test, and avoid the much larger influx of seniors that would occur if the asset test were eliminated entirely. PMID- 22323168 TI - Seizing opportunities under the Affordable Care Act for transforming the mental and behavioral health system. AB - The Affordable Care Act, along with Medicaid expansions, offers the opportunity to redesign the nation's highly flawed mental health system. It promotes new programs and tools, such as health homes, interdisciplinary care teams, the broadening of the Medicaid Home and Community-Based Services option, co-location of physical health and behavioral services, and collaborative care. Provisions of the act offer extraordinary opportunities, for instance, to insure many more people, reimburse previously unreimbursed services, integrate care using new information technology tools and treatment teams, confront complex chronic comorbidities, and adopt underused evidence-based interventions. The Centers for Medicare and Medicaid Services and its Center for Medicare and Medicaid Innovation should work intensively with the states to implement these new programs and other arrangements and begin to fulfill the many unmet promises of community mental health care. PMID- 22323169 TI - Survey shows that at least some physicians are not always open or honest with patients. AB - The Charter on Medical Professionalism, endorsed by more than 100 professional groups worldwide and the US Accreditation Council for Graduate Medical Education, requires openness and honesty in physicians' communication with patients. We present data from a 2009 survey of 1,891 practicing physicians nationwide assessing how widely physicians endorse and follow these principles in communicating with patients. The vast majority of physicians completely agreed that physicians should fully inform patients about the risks and benefits of interventions and should never disclose confidential information to unauthorized persons. Overall, approximately one-third of physicians did not completely agree with disclosing serious medical errors to patients, almost one-fifth did not completely agree that physicians should never tell a patient something untrue, and nearly two-fifths did not completely agree that they should disclose their financial relationships with drug and device companies to patients. Just over one tenth said they had told patients something untrue in the previous year. Our findings raise concerns that some patients might not receive complete and accurate information from their physicians, and doubts about whether patient centered care is broadly possible without more widespread physician endorsement of the core communication principles of openness and honesty with patients. PMID- 22323170 TI - Government can regulate food advertising to children because cognitive research shows that it is inherently misleading. AB - The childhood obesity crisis has prompted repeated calls for government action to curb the marketing of unhealthy food to children. Food and entertainment industry groups have asserted that the First Amendment prohibits such regulation. However, case law establishes that the First Amendment does not protect "inherently misleading" commercial speech. Cognitive research indicates that young children cannot effectively recognize the persuasive intent of advertising or apply the critical evaluation required to comprehend commercial messages. Given this combination--that government can prohibit "inherently misleading" advertising and that children cannot adequately understand commercial messages--advertising to children younger than age twelve should be considered beyond the scope of constitutional protection. PMID- 22323171 TI - Inviting consumers to downsize fast-food portions significantly reduces calorie consumption. AB - Policies that mandate calorie labeling in fast-food and chain restaurants have had little or no observable impact on calorie consumption to date. In three field experiments, we tested an alternative approach: activating consumers' self control by having servers ask customers if they wanted to downsize portions of three starchy side dishes at a Chinese fast-food restaurant. We consistently found that 14-33 percent of customers accepted the downsizing offer, and they did so whether or not they were given a nominal twenty-five-cent discount. Overall, those who accepted smaller portions did not compensate by ordering more calories in their entrees, and the total calories served to them were, on average, reduced by more than 200. We also found that accepting the downsizing offer did not change the amount of uneaten food left at the end of the meal, so the calorie savings during purchasing translated into calorie savings during consumption. Labeling the calorie content of food during one of the experiments had no measurable impact on ordering behavior. If anything, the downsizing offer was less effective in changing customers' ordering patterns with the calorie labeling present. These findings highlight the potential importance of portion-control interventions that specifically activate consumers' self-control. PMID- 22323172 TI - The financial burden from prescription drugs has declined recently for the nonelderly, although it is still high for many. AB - Prescription drug spending and pharmacy benefit design have changed greatly over the past decade. However, little is known about the financial impact these changes have had on consumers. We examined ten years of nationally representative data from the Medical Expenditure Panel Survey and describe trends in two measures of financial burden for prescription drugs: out-of-pocket drug costs as a function of family income and the proportion of all out-of-pocket health care expenses accounted for by drugs. We found that although the percentage of people with high financial burden for prescription drugs increased from 1999 to 2003, it decreased from 2003 to 2007, with a slight increase in 2008. The decline is evidence of the success of strategies to lower drug costs for consumers, including the increased use of generic drugs. However, the financial burden is still high among some groups, notably those with public insurance and those with low incomes. For example, one in four nonelderly people devote more than half of their total out-of-pocket health care spending to prescription drugs. These trends suggest that the affordability of prescription drugs under the future insurance exchanges will need to be monitored, as will efforts by states to increase prescription drug copayments under Medicaid or otherwise restrict drug use to reduce public spending. PMID- 22323173 TI - Study raises questions about measurement of 'additionality,'or maintaining domestic health spending amid foreign donations. AB - Donor nations and philanthropic organizations increasingly require that funds provided for a specific health priority such as HIV should supplement domestic spending on that priority-a concept known as "additionality." We investigated the "additionality" concept using data from Honduras, Rwanda, and Thailand, and we found that the three countries increased funding for HIV in response to increased donor funding. In contrast, the study revealed that donors, faced with increased Global Fund resources for HIV in certain countries, tended to decrease their funding for HIV or shift funds for use in non-HIV health areas. More broadly, we found many problems in the measurement and interpretation of additionality. These findings suggest that it would be preferable for donors and countries to agree on how best to use available domestic and external funds to improve population health, and to develop better means of tracking outcomes, than to try to develop more sophisticated methods to track additionality. PMID- 22323174 TI - Early results from adoption of bundled payment for diabetes care in the Netherlands show improvement in care coordination. AB - In 2010 a bundled payment system for diabetes care, chronic obstructive pulmonary disease care, and vascular risk management was introduced in the Netherlands. Health insurers now pay a single fee to a contracting entity, the care group, to cover all of the primary care needed by patients with these chronic conditions. The initial evaluation of the program indicated that it improved the organization and coordination of care and led to better collaboration among health care providers and better adherence to care protocols. Negative consequences included dominance of the care group by general practitioners, large price variations among care groups that were only partially explained by differences in the amount of care provided, and an administrative burden caused by outdated information and communication technology systems. It is too early to draw conclusions about the effects of the new payment system on the quality or the overall costs of care. However, the introduction of bundled payments might turn out to be a useful step in the direction of risk-adjusted integrated capitation payments for multidisciplinary provider groups offering primary and specialty care to a defined group of patients. PMID- 22323175 TI - A gravely ill patient faces the grim results of outliving her eligibility for hospice benefits. PMID- 22323178 TI - Confounding factors in off-label drug use. PMID- 22323180 TI - An incomplete book review. PMID- 22323182 TI - The representation of an author's views. PMID- 22323184 TI - The role of ATM and 53BP1 as predictive markers in cervical cancer. AB - Treatment of advanced-stage cervical cancers with (chemo)radiation causes cytotoxicity through induction of high levels of DNA damage. Tumour cells respond to DNA damage by activation of the 'DNA damage response' (DDR), which induces DNA repair and may counteract chemoradiation efficacy. Here, we investigated DDR components as potential therapeutic targets and verified the predictive and prognostic value of DDR activation in patients with cervical cancer treated with (chemo)radiation. In a panel of cervical cancer cell lines, inactivation of ataxia telangiectasia mutated (ATM) or its substrate p53-binding protein-1 (53BP1) clearly gave rise to cell cycle defects in response to irradiation. Concordantly, clonogenic survival analysis revealed that ATM inhibition, but not 53BP1 depletion, strongly radiosensitised cervical cancer cells. In contrast, ATM inhibition did not radiosensitise non-transformed epithelial cells or non transformed BJ fibroblasts. Interestingly, high levels of active ATM prior to irradiation were related with increased radioresistance. To test whether active ATM in tumours prior to treatment also resulted in resistance to therapy, immunohistochemistry was performed on tumour material of patients with advanced stage cervical cancer (n = 375) treated with (chemo)radiation. High levels of phosphorylated (p-)ATM [p = 0.006, hazard ratio (HR) = 1.817] were related to poor locoregional disease-free survival. Furthermore, high levels of p-ATM predicted shorter disease-specific survival (p = 0.038, HR = 1.418). The presence of phosphorylated 53BP1 was associated with p-ATM (p = 0.001, odds ratio = 2.206) but was not related to any clinicopathological features or survival. In conclusion, both our in vitro and patient-related findings indicate a protective role for ATM in response to (chemo)radiation in cervical cancer and point at ATM inhibition as a possible means to improve the efficacy of (chemo)radiation. PMID- 22323185 TI - Constructing self-identity: minority students' adaptation trajectories in a Chinese university. AB - Researchers have gone beyond identity status and been putting more and more emphases on the dynamic process of identity development and its contextual embeddedness. Study of individual's adaptation to the multicultural background is a good point of penetration. Because of the differences in regional conditions and cultural traditions, the minority youths who go to university in the mainstream culture would have special experiences and challenges in the development of their self-identities. Semi-structured interview and narrative were used in this research to discover the characteristics of the self-identity constructing processes of Mongolian undergraduates in a Shanghai university context. Their identity constructing process could be divided into three stages: difference-detecting, self-doubting and self-orienting. The main efforts of identity constructing in each stage could all be described as self-exploring and support-seeking. Special contents of internal explorations and sources of support were distinguished at different stages. As relative results, three main types of self-orientation were revealed: goal-oriented, self-isolated and unreserved assimilated. The characteristics of them are quite similar to those of three identity processing styles proposed by Berzonsky, which indicates there are some common elements lying in all self-development processes of adolescences and young adults. Ethnicity and culture could be background and resource or what Cote called identity capital that impacts the special course of self-identity constructing under similar principles. Different attitudes towards and relationships with their own ethnicity and new surroundings separated the three types of students from each other and interacted with the developmental characteristics and tendencies of their ethnicity identifications and self identities. It was found that minority youths' self-identity constructing was based on their needs of self-value and interacted with their ecological niche constructing. Take ethnicity attachment and ethnicity responsibility as a typical example: the setting up of bi-direction relationship between individuals and their ethnicity (or other identity-related factors) was very important for minority youths to expand and integrate themselves. We also presented in detail our methodological exploring process so as to illuminate the limitation of traditional methods and the necessity and importance of methodological reform. Methodologically, both emic and etic positions were taken, interview and narrative approaches were adopted and individual angle of analysis was kept in the research. They were all proved to be effective to provide insight into the dynamic process of self identity constructing. PMID- 22323186 TI - Comparison of high-throughput biophysical methods to identify stabilizing excipients for a model IgG2 monoclonal antibody: conformational stability and kinetic aggregation measurements. AB - The overall conformational stability of a model IgG2 monoclonal antibody (mAb) was examined as a function of temperature and pH using an empirical phase diagram approach. Stabilizing excipients were then identified based on high-throughput methods including (1) kinetic studies measuring aggregation via increases in optical density and (2) thermally induced structural transitions as measured by differential scanning calorimetry (DSC) and fluorescence spectroscopy. The kinetic profiles of antibody aggregation at 65 degrees C were pH dependent and correlated well with pH effects on secondary and tertiary structural transitions due to heat stress. For the screening of stabilizing excipients, the inhibition of the rate of protein aggregation at pH 4.5 at 65 degrees C, as represented by changes in optical density, was shown to have a clear trend with a modest correlation coefficient compared with the stabilizing effect of the same excipients on the conformational stability of the antibody as measured by DSC and tryptophan fluorescence spectroscopy. These results demonstrate the utility of combining high-throughput data from protein aggregation kinetic experiments and conformational stability studies to identify stabilizing excipients that minimize the physical degradation of an IgG2 mAb. PMID- 22323188 TI - What, another Nobel Prize in chemistry to a nonchemist? PMID- 22323187 TI - Retraction note to: Molecular cloning, sequence characterization, and tissue expression analysis of Hi-line brown chicken Akirin2. PMID- 22323189 TI - Expression of dominant-negative Ikaros isoforms and associated genetic alterations in Chinese adult patients with leukemia. AB - Dominant-negative (DN) Ikaros isoforms, having important roles in pathogenesis of leukemia, are mainly studied in pediatric patients, but little is known about Chinese adult patients. We examined 339 Chinese adult patients with leukemia and demonstrated the different findings between our results and those in several previous studies showing that DN isoforms overexpressed in Philadelphia chromosome positive acute lymphoblastic leukemia (Ph(+)ALL) and lymphoid/mixed blast crisis of chronic myelogenous leukemia. We confirmed that deletion of IKZF1 gene exons 4-7 is responsible for the generation of Ikaros 6 (Ik6). Moreover, we observed that expression of DN isoforms was dynamically consistent with BCR-ABL1 transcript levels, associated with higher incidence of relapse within 3 months or poor response to induction chemotherapy in Ph(+)ALL, correlated with high white blood cell, blast cells, CD34 positive cells, and delayed achieving complete hematological remission in ALL patients. In conclusion, this study provides a rationale for the integration of aberrant Ikaros isoforms, notably Ik6 and Ik10, in the evaluation of adult ALL, particularly in Ph(+)ALL patients. PMID- 22323190 TI - Tandem solid phase extraction followed by online trapping-hydrophilic interaction chromatography-tandem mass spectrometry for sensitive detection of endogenous cytokinins in plant tissues. AB - INTRODUCTION: Cytokinins (CKs) are a group of plant hormones that play pivotal roles at low concentration in plant growth, development and regulatory pathways. In order to study the function, metabolism and signal transduction of CKs, high performance analytical techniques are required for determination of their endogenous levels. OBJECTIVE: To develop a highly sensitive, selective and reliable method for identification and quantification of CKs by employing a tandem solid phase extraction (SPE)-online trapping-hydrophilic interaction chromatography (HILIC)-MS/MS method. MATERIAL AND METHODS: The extraction was performed firstly with tandem SPE containing a C(18) cartridge and a silica@C(8) /SO(3) H cartridge. After CKs were eluted from the silica@C(8)/SO(3) H cartridge, the desorption solvent was concentrated and redissolved in H(2)O and then injected into the online trapping-HILIC-MS/MS system with (Poly(MAA-co-EGDMA)) monolith as the trapping column. Subsequently, trapping, washing, desorption, separation and detection were accomplished automatically on the system. RESULTS: Good linearities were obtained for eight cytokinins with correlation coefficients (R(2)) > 0.9964. The limits of detection (LOD; S:N = 3) for the targets ranged from 0.042 to 1.6 pg/mL. Reproducibility of the method was evaluated with intraday and interday relative standard deviations (RSDs) less than 13.4% and the recoveries ranged from 77.3% to 116.3%. The results showed that the LOD of the analytical method were at least one order of magnitude lower compared with other previously reported methods. Furthermore, only 20 mg of plant tissues were required for the quantitative analysis of the major CKs, which is, to the best of our knowledge, the smallest amount reported so far for the determination of endogenous CKs in plant tissues. CONCLUSION: The tandem SPE-online trapping-HILIC MS/MS method developed in current study provides a powerful tool for the convenient and highly sensitive quantification of the major CKs in plant tissue. PMID- 22323191 TI - Truncated reverse isoxazolidinyl nucleosides: a new class of allosteric HIV-1 reverse transcriptase inhibitors. PMID- 22323192 TI - Physical gills prevent drowning of many wetland insects, spiders and plants. AB - Insects, spiders and plants risk drowning in their wetland habitats. The slow diffusion of O(2) can cause asphyxiation when underwater, as O(2) supply cannot meet respiratory demands. Some animals and plants have found a common solution to the major challenge: how to breathe underwater with respiratory systems evolved for use in air? Hydrophobic surfaces on their bodies possess gas films that act as a 'physical gill' to collect O(2) when underwater and thus sustain respiration. In aquatic insects, this feature/process has been termed 'plastron respiration'. Here, we demonstrate the similarities in function between underwater respiration of insect (Aphelocheirus aestivalis) plastrons and gas films on leaves of wetland plants (Phalaris arundinacea) and also show the importance of these physical gills by the resulting changes upon their removal. The gas films provide an enlarged gas-water interface to enhance O(2) uptake underwater that is above that if only spiracles (insects) or stomata (plants) provided the gas-phase contact with the water. Body-surface gas films contribute to the survival of many insects, spiders and plants in aquatic and flood-prone environments. PMID- 22323193 TI - Scaling of wingbeat frequency with body mass in bats and limits to maximum bat size. AB - The ability to fly opens up ecological opportunities but flight mechanics and muscle energetics impose constraints, one of which is that the maximum body size must be kept below a rather low limit. The muscle power available for flight increases in proportion to flight muscle mass and wingbeat frequency. The maximum wingbeat frequency attainable among increasingly large animals decreases faster than the minimum frequency required, so eventually they coincide, thereby defining the maximum body mass at which the available power just matches up to the power required for sustained aerobic flight. Here, we report new wingbeat frequency data for 27 morphologically diverse bat species representing nine families, and additional data from the literature for another 38 species, together spanning a range from 2.0 to 870 g. For these species, wingbeat frequency decreases with increasing body mass as M(b)(-0.26). We filmed 25 of our 27 species in free flight outdoors, and for these the wingbeat frequency varies as M(b)(-0.30). These exponents are strikingly similar to the body mass dependency M(b)(-0.27) among birds, but the wingbeat frequency is higher in birds than in bats for any given body mass. The downstroke muscle mass is also a larger proportion of the body mass in birds. We applied these empirically based scaling functions for wingbeat frequency in bats to biomechanical theories about how the power required for flight and the power available converge as animal size increases. To this end we estimated the muscle mass-specific power required for the largest flying extant bird (12-16 kg) and assumed that the largest potential bat would exert similar muscle mass-specific power. Given the observed scaling of wingbeat frequency and the proportion of the body mass that is made up by flight muscles in birds and bats, we estimated the maximum potential body mass for bats to be 1.1-2.3 kg. The largest bats, extinct or extant, weigh 1.6 kg. This is within the range expected if it is the bat characteristic flight muscle mass and wingbeat frequency that limit the maximum body mass in bats. It is only a tenth the mass of the largest flying extant bird. PMID- 22323194 TI - How to make a sexy snake: estrogen activation of female sex pheromone in male red sided garter snakes. AB - Vertebrates indicate their genetic sex to conspecifics using secondary sexual signals, and signal expression is often activated by sex hormones. Among vertebrate signaling modalities, the least is known about how hormones influence chemical signaling. Our study species, the red-sided garter snake (Thamnophis sirtalis parietalis), is a model vertebrate for studying hormonal control of chemical signals because males completely rely on the female sex pheromone to identify potential mates among thousands of individuals. How sex hormones can influence the expression of this crucial sexual signal is largely unknown. We created two groups of experimental males for the first experiment: Sham (blank implants) and E2 (17beta-estradiol implants). E2 males were vigorously courted by wild males in outdoor bioassays, and in a Y-maze E2 pheromone trails were chosen by wild males over those of small females and were indistinguishable from large female trails. Biochemically, the E2 pheromone blend was similar to that of large females, and it differed significantly from Shams. For the second experiment, we implanted males with 17beta-estradiol in 2007 but removed the implants the following year (2008; Removal). That same year, we implanted a new group of males with estrogen implants (Implant). Removal males were courted by wild males in 2008 (implant intact) but not in 2009 (removed). Total pheromone quantity and quality increased following estrogen treatment, and estrogen removal re established male-typical pheromone blends. Thus, we have shown that estrogen activates the production of female pheromone in adult red-sided garter snakes. This is the first known study to quantify both behavioral and biochemical responses in chemical signaling following sex steroid treatment of reptiles in the activation/organization context. We propose that the homogametic sex (ZZ, male) may possess the same targets for activation of sexual signal production, and the absence of the activator (17beta-estradiol in this case) underlies expression of the male phenotype. PMID- 22323195 TI - Net superoxide levels: steeper increase with activity in cooler female and hotter male lizards. AB - Ectotherms increase their body temperature in response to ambient heat, thereby elevating their metabolic rate. An often inferred consequence of this is an overall upregulation of gene expression and energetic expenditure, and a concomitant increased production of reactive oxygen species (e.g. superoxide) and, perhaps, a shortened lifespan. However, recent work shows that this may be a superficial interpretation. For example, sometimes a reduced temperature may in fact trigger up-regulation of gene expression. We studied temperature and associated activity effects in male and female Australian painted dragon lizards (Ctenophorus pictus) by allowing the lizards to bask for 4 h versus 12 h, and scoring their associated activity (inactive versus active basking and foraging). As predicted, long-basking lizards (hereafter 'hot') showed heightened activity in both sexes, with a more pronounced effect in females. We then tested for sex specific effects of basking treatment and activity levels on the increase in net levels of superoxide. In males, short-baskers (hereafter 'cold') had significantly more rapidly decreasing levels of superoxide per unit increasing activity than hot males. In females, however, superoxide levels increased faster with increasing activity in the cold than in the hot basking treatment, and females earlier in the ovarian cycle had lower superoxide levels than females closer to ovulation. In short, males and females differ in how their levels of reactive oxygen species change with temperature-triggered activity. PMID- 22323196 TI - Polarotactic tabanids find striped patterns with brightness and/or polarization modulation least attractive: an advantage of zebra stripes. AB - The characteristic striped appearance of zebras has provoked much speculation about its function and why the pattern has evolved, but experimental evidence is scarce. Here, we demonstrate that a zebra-striped horse model attracts far fewer horseflies (tabanids) than either homogeneous black, brown, grey or white equivalents. Such biting flies are prevalent across Africa and have considerable fitness impact on potential mammalian hosts. Besides brightness, one of the likely mechanisms underlying this protection is the polarization of reflected light from the host animal. We show that the attractiveness of striped patterns to tabanids is also reduced if only polarization modulations (parallel stripes with alternating orthogonal directions of polarization) occur in horizontal or vertical homogeneous grey surfaces. Tabanids have been shown to respond strongly to linearly polarized light, and we demonstrate here that the light and dark stripes of a zebra's coat reflect very different polarizations of light in a way that disrupts the attractiveness to tabanids. We show that the attractiveness to tabanids decreases with decreasing stripe width, and that stripes below a certain size are effective in not attracting tabanids. Further, we demonstrate that the stripe widths of zebra coats fall in a range where the striped pattern is most disruptive to tabanids. The striped coat patterns of several other large mammals may also function in reducing exposure to tabanids by similar mechanisms of differential brightness and polarization of reflected light. This work provides an experimentally supported explanation for the underlying mechanism leading to the selective advantage of a black-and-white striped coat pattern. PMID- 22323197 TI - Mechanisms underlying parallel reductions in aerobic capacity in non-migratory threespine stickleback (Gasterosteus aculeatus) populations. AB - Non-migratory, stream-resident populations of threespine stickleback, Gasterosteus aculeatus, have a lower maximum oxygen consumption ((O(2),max)) than ancestral migratory marine populations. Here, we examined laboratory-bred stream resident and marine crosses from two locations (West and Bonsall Creeks) to determine which steps in the oxygen transport and utilization cascade evolved in conjunction with, and thus have the potential to contribute to, these differences in (O(2),max). We found that West Creek stream-resident fish have larger muscle fibres (not measured in Bonsall fish), Bonsall Creek stream-resident fish have smaller ventricles, and both stream-resident populations have evolved smaller pectoral adductor and abductor muscles. However, many steps of the oxygen cascade did not evolve in stream-resident populations (gill surface area, hematocrit, mean cellular hemoglobin content and the activities of mitochondrial enzymes per gram ventricle and pectoral muscle), arguing against symmorphosis. We also studied F1 hybrids to determine which traits in the oxygen cascade have a genetic architecture similar to that of (O(2),max). In West Creek, (O(2),max), abductor and adductor size all showed dominance of marine alleles, whereas in Bonsall Creek, (O(2),max) and ventricle mass showed dominance of stream-resident alleles. We also found genetically based differences among marine populations in hematocrit, ventricle mass, pectoral muscle mass and pectoral muscle pyruvate kinase activity. Overall, reductions in pectoral muscle mass evolved in conjunction with reductions in (O(2),max) in both stream-resident populations, but the specific steps in the oxygen cascade that have a genetic basis similar to that of (O(2),max), and are thus predicted to have the largest impact on (O(2),max), differ among populations. PMID- 22323198 TI - Stable isotope tracer reveals that viviparous snakes transport amino acids to offspring during gestation. AB - Viviparity and placentation have evolved from oviparity over 100 times in squamate reptiles (lizards and snakes). The independent origins of placentation have resulted in a variety of placental morphologies in different taxa, ranging from simple apposition of fetal and maternal tissues to endotheliochorial implantation that is homoplasious with mammalian placentation. Because the eggs of oviparous squamates transport gases and water from the environment and calcium from the eggshell, the placentae of viviparous squamates are thought to have initially evolved to accomplish these functions from within the maternal oviduct. Species with complex placentae have also been shown to rely substantially, or even primarily, on placental transport of organic nutrients for embryonic nutrition. However, it is unclear whether species with only simple placentae are also capable of transporting organic nutrients to offspring. Among viviparous squamates, all of the snakes that have been studied thus far have been shown to have simple placentae. However, most studies of snake placentation are limited to a single lineage, the North American Natricinae. We tested the abilities of four species of viviparous snakes - Agkistrodon contortrix (Viperidae), Boa constrictor (Boidae), Nerodia sipedon (Colubridae: Natricinae) and Thamnophis sirtalis (Colubridae: Natricinae) - to transport diet-derived amino acids to offspring during gestation. We fed [(15)N]leucine to pregnant snakes, and compared offspring (15)N content with that of unlabeled controls. Labeled females allocated significantly more (15)N to offspring than did controls, but (15)N allocation did not differ among species. Our results indicate that viviparous snakes are capable of transporting diet-derived amino acids to their offspring during gestation, possibly via placentation. PMID- 22323199 TI - Geometry of compensatory feeding and water consumption in Drosophila melanogaster. AB - Feeding behaviour is an expression of an animal's underlying nutritional strategy. The study of feeding decisions can hence delineate nutritional strategies. Studies of Drosophila melanogaster feeding behaviour have yielded conflicting accounts, and little is known about how nutrients affect feeding patterns in this important model species. Here, we conducted two experiments to characterize nutrient prioritization and regulation. In a choice experiment, we allowed female flies to self-regulate their intake of yeast, sucrose and water by supplying individual flies with three microcapillary tubes: one containing only yeast of varying concentrations, another with just sucrose of varying concentrations, and the last with just water. Flies tightly regulated yeast and sucrose to a constant ratio at the expense of excess water intake, indicating that flies prioritize macronutrient regulation over excess water consumption. To determine the relative importance of yeast and sucrose, in a no-choice experiment, we provided flies with two microcapillary tubes: the first with one of the 28 diets varying in yeast and sucrose content and the other with only water. Flies increased total water intake in relation to yeast consumption but not sucrose consumption. Additionally, flies increased diet intake as diet concentration decreased and as the ratio of sugar to yeast equalized. Using a geometric scaling approach, we found that the patterns of diet intake can be explained by flies prioritizing protein and carbohydrates equally and by the lack of substitutability between the nutrients. We conclude by illustrating how our results harmonize conflicting results in the literature once viewed in a two dimensional diet landscape. PMID- 22323200 TI - Effects of different substrates on the sprint performance of lizards. AB - The variation in substrate structure is one of the most important determinants of the locomotor abilities of lizards. Lizards are found across a range of habitats, from large rocks to loose sand, each of them with conflicting mechanical demands on locomotion. We examined the relationships among sprint speed, morphology and different types of substrate surfaces in species of lizards that exploit different structural habitats (arboreal, saxicolous, terrestrial and arenicolous) in a phylogenetic context. Our main goals were to assess which processes drive variability in morphology (i.e. phylogeny or adaptation to habitat) in order to understand how substrate structure affects sprint speed in species occupying different habitats and to determine the relationship between morphology and performance. Liolaemini lizards show that most morphological traits are constrained by phylogeny, particularly toe 3, the femur and foot. All ecological groups showed significant differences on rocky surfaces. Surprisingly, no ecological group performed better on the surface resembling its own habitat. Moreover, all groups exhibited significant differences in sprint speed among the three different types of experimental substrates and showed the best performance on sand, with the exception of the arboreal group. Despite the fact that species use different types of habitats, the highly conservative morphology of Liolaemini species and the similar levels of performance on different types of substrates suggest that they confer to the 'jack of all trades and master of none' principle. PMID- 22323201 TI - The hydrodynamic function of shark skin and two biomimetic applications. AB - It has long been suspected that the denticles on shark skin reduce hydrodynamic drag during locomotion, and a number of man-made materials have been produced that purport to use shark-skin-like surface roughness to reduce drag during swimming. But no studies to date have tested these claims of drag reduction under dynamic and controlled conditions in which the swimming speed and hydrodynamics of shark skin and skin-like materials can be quantitatively compared with those of controls lacking surface ornamentation or with surfaces in different orientations. We use a flapping foil robotic device that allows accurate determination of the self-propelled swimming (SPS) speed of both rigid and flexible membrane-like foils made of shark skin and two biomimetic models of shark skin to measure locomotor performance. We studied the SPS speed of real shark skin, a silicone riblet material with evenly spaced ridges and a Speedo(r) 'shark skin-like' swimsuit fabric attached to rigid flat-plate foils and when made into flexible membrane-like foils. We found no consistent increase in swimming speed with Speedo(r) fabric, a 7.2% increase with riblet material, whereas shark skin membranes (but not rigid shark skin plates) showed a mean 12.3% increase in swimming speed compared with the same skin foils after removing the denticles. Deformation of the shark skin membrane is thus crucial to the drag reducing effect of surface denticles. Digital particle image velocimetry (DPIV) of the flow field surrounding moving shark skin foils shows that skin denticles promote enhanced leading-edge suction, which might have contributed to the observed increase in swimming speed. Shark skin denticles might thus enhance thrust, as well as reduce drag. PMID- 22323202 TI - Papiliochrome II pigment reduces the angle dependency of structural wing colouration in nireus group papilionids. AB - The wings of four papilionid butterfly species of the nireus group, Papilio bromius, P. epiphorbas, P. nireus and P. oribazus, are marked by blue-green coloured bands surrounded by black margins. The cover scales in the coloured bands contain a violet-absorbing, blue-fluorescing pigment. The fluorescence and absorbance spectra of the nireus group wings are very similar to those of the wings of the Japanese yellow swallowtail, Papilio xuthus, and thus the pigment is presumably papiliochrome II. The scale structures of P. xuthus are arranged irregularly, and both the fluorescence and light reflection are diffuse. In the nireus papilionids, the spatial fluorescence distribution of the scales is also diffuse, but the reflection is specular. The scales have a multilayered structure, consisting of two main laminae. We show that the papiliochrome II pigment in the upper lamina of the scales functions as a violet-blocking long pass filter in front of the lower lamina, thus limiting the reflectance spectrum to the blue-green wavelength range. Optical modelling showed that the papiliochrome II filter effectively removes the angle dependency of the reflectance spectra - that is, it reduces the wing iridescence. The contribution of the fluorescence signal to the visual appearance is minor. PMID- 22323203 TI - In the face of hypoxia: myoglobin increases in response to hypoxic conditions and lipid supplementation in cultured Weddell seal skeletal muscle cells. AB - A key cellular adaptation to diving in Weddell seals is enhanced myoglobin concentrations in their skeletal muscles, which serve to store oxygen to sustain a lipid-based aerobic metabolism. The aim of this study was to determine whether seal muscle cells are inherently adapted to possess the unique skeletal muscle adaptations to diving seen in the whole animal. We hypothesized that the seal skeletal muscle cells would have enhanced concentrations of myoglobin de novo that would be greater than those from a C(2)C(12) skeletal muscle cell line and reflect the concentrations of myoglobin observed in previous studies. In addition we hypothesized that the seal cells would respond to environmental hypoxia similarly to the C(2)C(12) cells in that citrate synthase activity and myoglobin would remain the same or decrease under hypoxia and lactate dehydrogenase activity would increase under hypoxia as previously reported. We further hypothesized that beta-hydroxyacyl CoA dehydrogenase activity would increase in response to the increasing amounts of lipid supplemented to the culture medium. Our results show that myoglobin significantly increases in response to environmental hypoxia and lipids in the Weddell seal cells, while appearing similar metabolically to the C(2)C(12) cells. The results of this study suggest the regulation of myoglobin expression is fundamentally different in Weddell seal skeletal muscle cells when compared with a terrestrial mammalian cell line in that hypoxia and lipids initially prime the skeletal muscles for enhanced myoglobin expression. However, the cells need a secondary stimulus to further increase myoglobin to levels seen in the whole animal. PMID- 22323204 TI - Aging modulates cuticular hydrocarbons and sexual attractiveness in Drosophila melanogaster. AB - Attractiveness is a major component of sexual selection that is dependent on sexual characteristics, such as pheromone production, which often reflect an individual's fitness and reproductive potential. Aging is a process that results in a steady decline in survival and reproductive output, yet little is known about its effect on specific aspects of attractiveness. In this report we asked how aging impacts pheromone production and sexual attractiveness in Drosophila melanogaster. Evidence suggests that key pheromones in Drosophila are produced as cuticular hydrocarbons (CHC), whose functions in attracting mates and influencing behavior have been widely studied. We employed gas chromatography/mass spectrometry and laser desorption/ionization mass spectrometry to show that the composition of D. melanogaster CHC is significantly affected by aging in both sexes and that these changes are robust to different genetic backgrounds. Aging affected the relative levels of many individual CHC, and it shifted overall hydrocarbon profiles to favor compounds with longer chain lengths. We also show that the observed aging-related changes in CHC profiles are responsible for a significant reduction in sexual attractiveness. These studies illuminate causal links among pheromones, aging and attractiveness and suggest that CHC production may be an honest indicator of animal health and fertility. PMID- 22323205 TI - Copper and zinc detoxification in Gammarus pulex (L.). AB - To negate the toxicity of labile intracellular metals, some aquatic organisms partition metals into specific subcellular locations for detoxification, namely the soluble heat-stable cytosol and insoluble metal-rich granules. The aim of the present study was to characterise these subcellular storage sites in the freshwater crustacean Gammarus pulex (Linnaeus) following in situ exposures upstream (Drym, low metal) and downstream (Relubbus, elevated metal) of copper- and zinc-rich inflows into the River Hayle (Cornwall, UK). In the cytosol of gammarids exposed at Relubbus, copper and zinc associated to a 7.5-kDa metallothionein-like protein (MTLP) that was largely absent from gammarids prior to exposure. Exposure at Relubbus caused MTLP concentrations to increase 4- to 5 fold between days 2 and 4, indicating an induction response to increased labile intracellular metal. On day 16, spherical calcium-rich granules (0.5-2.5 MUmol l( 1)) were visualised and analysed in the posterior caeca of gammarids exposed at both sites. Following exposure at Relubbus, granules contained trace amounts of copper, but zinc was absent. Granules in gammarids exposed at Drym contained no detectable copper or zinc. Granule formation appeared to be independent of exposure. Within the posterior caeca, granules have been associated with calcium storage during the crustacean molt, rather than in detoxification of trace metals. However, the granular copper burden appeared to follow environmental Cu availabilities. Thus, we describe Cu sequestration within molt-cycle calcium storage granules. As both MTLP concentrations and granule formation in crustaceans are affected upon by molting, we hypothesise that detoxification might impact upon this existing process. PMID- 22323206 TI - Is solid always best? Cranial performance in solid and fenestrated caecilian skulls. AB - Caecilians (Lissamphibia: Gymnophiona) are characterized by a fossorial lifestyle that appears to play a role in the many anatomical specializations in the group. The skull, in particular, has been the focus of previous studies because it is driven into the substrate for burrowing. There are two different types of skulls in caecilians: (1) stegokrotaphic, where the squamosal completely covers the temporal region and the jaw closing muscles, and (2) zygokrotaphic, with incomplete coverage of the temporal region by the squamosal. We used 3-D imaging and modeling techniques to explore the functional consequences of these skull types in an evolutionary context. We digitally converted stegokrotaphic skulls into zygokrotaphic skulls and vice versa. We also generated a third, akinetic skull type that was presumably present in extinct caecilian ancestors. We explored the benefits and costs of the different skull types under frontal loading at different head angles with finite element analysis (FEA). Surprisingly, the differences in stress distributions and bending between the three tested skull types were minimal and not significant. This suggests that the open temporal region in zygokrotaphic skulls does not lead to poorer performance during burrowing. However, the results of the FEA suggest a strong relationship between the head angle and skull performance, implying there is an optimal head angle during burrowing. PMID- 22323207 TI - The accessory role of the diaphragmaticus muscle in lung ventilation in the estuarine crocodile Crocodylus porosus. AB - Crocodilians use a combination of three muscular mechanisms to effect lung ventilation: the intercostal muscles producing thoracic movement, the abdominal muscles producing pelvic rotation and gastralial translation, and the diaphragmaticus muscle producing visceral displacement. Earlier studies suggested that the diaphragmaticus is a primary muscle of inspiration in crocodilians, but direct measurements of the diaphragmatic contribution to lung ventilation and gas exchange have not been made to date. In this study, ventilation, metabolic rate and arterial blood gases were measured from juvenile estuarine crocodiles under three conditions: (i) while resting at 30 degrees C and 20 degrees C; (ii) while breathing hypercapnic gases; and (iii) during immediate recovery from treadmill exercise. The relative contribution of the diaphragmaticus was then determined by obtaining measurements before and after transection of the muscle. The diaphragmaticus was found to make only a limited contribution to lung ventilation while crocodiles were resting at 30 degrees C and 20 degrees C, and during increased respiratory drive induced by hypercapnic gas. However, the diaphragmaticus muscle was found to play a significant role in facilitating a higher rate of inspiratory airflow in response to exercise. Transection of the diaphragmaticus decreased the exercise-induced increase in the rate of inspiration (with no compensatory increases in the duration of inspiration), thus compromising the exercise-induced increases in tidal volume and minute ventilation. These results suggest that, in C. porosus, costal ventilation alone is able to support metabolic demands at rest, and the diaphragmaticus is largely an accessory muscle used at times of elevated metabolic demand. PMID- 22323208 TI - Dietary protein quality differentially regulates trypsin enzymes at the secretion and transcription level in Panulirus argus by distinct signaling pathways. AB - The effects of pelleted diets with different protein composition (fish, squid or soybean meals as main protein sources) on trypsin secretion and expression were studied in the lobster Panulirus argus. Trypsin secretion was shown to be maximal 4 h after ingestion. At this time, fish- and squid-based diets induced trypsin secretion, as well as up-regulation of the major trypsin isoform at the transcription level. While fish- and squid-based diets elicited a prandial response, soybean-based diet failed to stimulate the digestive gland to secrete trypsin into the gastric fluid or induce trypsin expression above the levels observed in fasting lobsters. In vitro assays showed that intact proteins rather than protein hydrolysates stimulate trypsin secretion in the lobster. However, the signal for trypsin transcription appears to be different to that for secretion and is probably mediated by the appearance of free amino acids in the digestive gland, suggesting a stepwise regulation of trypsin enzymes during digestion. We conclude that trypsin enzymes in P. argus are regulated at the transcription and secretion level by the quality of dietary proteins through two distinct signaling pathways. Our results indicate that protein digestion efficiency in spiny lobsters can be improved by selecting appropriated protein sources. However, other factors like the poor solubility of dietary proteins in dry diets could hamper further enhancement of digestion efficiency. PMID- 22323209 TI - Alteration of mitochondrial efficiency affects oxidative balance, development and growth in frog (Rana temporaria) tadpoles. AB - Mitochondria are known to play a central role in life history processes, being the main source of reactive oxygen species (ROS), which promote oxidative constraint. Surprisingly, although the main role of the mitochondria is to produce ATP, the plasticity of mitochondrial ATP generation has received little attention in life history studies. Yet, mitochondrial energy transduction represents the physiological link between environmental resources and energy allocated to animal performance. Studying both facets of mitochondrial functioning (ATP and ROS production) would allow better understanding of the proximate mechanisms underlying life history. We have experimentally modulated the mitochondrial capacity to generate ROS and ATP during larval development of Rana temporaria tadpoles, via chronic exposure (34 days) to a mitochondrial uncoupler (2,4-dinitrophenol, dNP). The aim was to better understand the impact of mitochondrial uncoupling on both responses in terms of oxidative balance, energy input (oxygen and feeding consumption) and energy output (growth and development of the tadpole). Exposure to 2,4-dNP reduced mitochondrial ROS generation, total antioxidant defences and oxidative damage in treated tadpoles compared with controls. Despite the beneficial effect of dNP on oxidative status, development and growth rates of treated tadpoles were lower than those in the control group. Treatment of tadpoles with 2,4-dNP promoted a mild mitochondrial uncoupling and enhanced metabolic rate. These tadpoles did not increase their food consumption, and thus failed to compensate for the energy loss elicited by the decrease in the efficiency of ATP production. These data suggest that the cost of ATP production, rather than the oxidative balance, is the parameter that constrains growth/development of tadpoles, highlighting the central role of energy transduction in larval performance. PMID- 22323210 TI - Uric acid levels predict survival in men with amyotrophic lateral sclerosis. AB - Elevated uric acid levels have recently been found to be associated with slower disease progression in Parkinson's disease, Huntington's disease, multiple system atrophy, and mild cognitive impairment. The aim of this study is to determine whether serum uric acid levels predict survival in amyotrophic lateral sclerosis (ALS). A total of 251 people with ALS enrolled in two multicenter clinical trials were included in our analysis. The main outcome measure was survival time, which was calculated as time to death, tracheostomy, or permanent assistive ventilation, with any event considered a survival endpoint. Cox proportional hazards models were used to estimate the hazard ratio (HR) of reaching a survival endpoint according to baseline uric acid levels after adjusting for markers of disease severity (FVC, total ALSFRS-R score, time since symptom onset, diagnostic delay, BMI, bulbar vs. spinal onset, age, and riluzole use). There was a dose dependent survival advantage in men, but not women, with higher baseline uric acid levels (logrank test: p = 0.018 for men, p = 0.81 for women). There was a 39% reduction in risk of death during the study for men with each 1 mg/dl increase in uric acid levels (adjusted HR: 0.61, 95% CI 0.39-0.96, p = 0.03). This is the first study to demonstrate that serum uric acid is associated with prolonged survival in ALS, after adjusting for markers of disease severity. Similar to previous reports in Parkinson's disease, this association was seen in male subjects only. PMID- 22323211 TI - Frontotemporal dementia with psychosis, parkinsonism, visuo-spatial dysfunction, upper motor neuron involvement associated to expansion of C9ORF72: a peculiar phenotype? PMID- 22323212 TI - SPECT-DTPA as a tool for evaluating the blood-brain barrier in post-stroke seizures. AB - Stroke is a well-known cause for seizures in the adult population. Research in animal models indicates that abnormalities in the blood-brain barrier (BBB) permeability can play a role in the development of spontaneous seizures or status epilepticus. The integrity of the BBB was investigated in patients with late post stroke seizures by performing DTPA-SPECT studies to evaluate the correlation of BBB dysfunction in late post-stroke seizures. All patients with late-onset post cortical stroke seizures hospitalized during 2009-2010 underwent a brain DTPA SPECT within 72 h of the first seizure and were compared to a control group of stroke patients without seizures. Twenty-eight patients were included in the study. Twelve out of 14 (85.7%) in the group of seizure post-stroke patients had a positive brain DTPA-SPECT showing disruption of the BBB in the region of the stroke respective to four patients out of 14 (28.6%) in the control group of stroke patients without seizures (p = 0.001). The results of this study suggest that there is a correlation between late post-stroke seizures and BBB disruption, as revealed by DTPA-SPECT examination. Perhaps, this finding could lead to the hypothesis that the BBB disruption can predict developing seizures in patients with cortical stroke. PMID- 22323214 TI - The immune inhibitory complex CD200/CD200R is developmentally regulated in the mouse brain. AB - The CD200/CD200R inhibitory immune ligand-receptor system regulates microglial activation/quiescence in adult brain. Here, we investigated CD200/CD200R at different stages of postnatal development, when microglial maturation takes place. We characterized the spatiotemporal, cellular, and quantitative expression pattern of CD200 and CD200R in the developing and adult C57/BL6 mice brain by immunofluorescent labeling and Western blotting. CD200 expression increased from postnatal day 1 (P1) to P5-P7, when maximum levels were found, and decreased to adulthood. CD200 was located surrounding neuronal bodies, and very prominently in cortical layer I, where CD200(+) structures included glial fibrillary acidic protein (GFAP)(+) astrocytes until P7. In the hippocampus, CD200 was mainly observed in the hippocampal fissure, where GFAP(+) /CD200(+) astrocytes were also found until P7. CD200(+) endothelium was seen in the hippocampal fissure and cortical blood vessels, notably from P14, showing maximum vascular CD200 in adults. CD200R(+) cells were a population of ameboid/pseudopodic Iba1(+) microglia/macrophages observed at all ages, but significantly decreasing with increasing age. CD200R(+) /Iba1(+) macrophages were prominent in the pial meninges and ventricle lining, mainly at P1-P5. CD200R(+) /Iba1(+) perivascular macrophages were observed in cortical and hippocampal fissure blood vessels, showing maximum density at P7, but being prominent until adulthood. CD200R(+) /Iba1(+) ameboid microglia in the cingulum at P1-P5 were the only CD200R(+) cells in the nervous tissue. In conclusion, the main sites of CD200/CD200R interaction seem to include the molecular layer and pial surface in neonates and blood vessels from P7 until adulthood, highlighting the possible role of the CD200/CD200R system in microglial development and renewal. PMID- 22323215 TI - Classification of proteins: available structural space for molecular modeling. AB - The wealth of available protein structural data provides unprecedented opportunity to study and better understand the underlying principles of protein folding and protein structure evolution. A key to achieving this lies in the ability to analyse these data and to organize them in a coherent classification scheme. Over the past years several protein classifications have been developed that aim to group proteins based on their structural relationships. Some of these classification schemes explore the concept of structural neighbourhood (structural continuum), whereas other utilize the notion of protein evolution and thus provide a discrete rather than continuum view of protein structure space. This chapter presents a strategy for classification of proteins with known three dimensional structure. Steps in the classification process along with basic definitions are introduced. Examples illustrating some fundamental concepts of protein folding and evolution with a special focus on the exceptions to them are presented. PMID- 22323216 TI - Effective techniques for protein structure mining. AB - Retrieval and characterization of protein structure relationships are instrumental in a wide range of tasks in structural biology. The classification of protein structures (COPS) is a web service that provides efficient access to structure and sequence similarities for all currently available protein structures. Here, we focus on the application of COPS to the problem of template selection in homology modeling. PMID- 22323217 TI - Methods for sequence-structure alignment. AB - Homology modeling is based on the observation that related protein sequences adopt similar three-dimensional structures. Hence, a homology model of a protein can be derived using related protein structure(s) as modeling template(s). A key step in this approach is the establishment of correspondence between residues of the protein to be modeled and those of modeling template(s). This step, often referred to as sequence-structure alignment, is one of the major determinants of the accuracy of a homology model. This chapter gives an overview of methods for deriving sequence-structure alignments and discusses recent methodological developments leading to improved performance. However, no method is perfect. How to find alignment regions that may have errors and how to make improvements? This is another focus of this chapter. Finally, the chapter provides a practical guidance of how to get the most of the available tools in maximizing the accuracy of sequence-structure alignments. PMID- 22323218 TI - Force fields for homology modeling. AB - Accurate all-atom energy functions are crucial for successful high-resolution protein structure prediction. In this chapter, we review both physics-based force fields and knowledge-based potentials used in protein modeling. Because it is important to calculate the energy as accurately as possible given the limitations imposed by sampling convergence, different components of the energy, and force fields representing them to varying degrees of detail and complexity are discussed. Force fields using Cartesian as well as torsion angle representations of protein geometry are covered. Since solvent is important for protein energetics, different aqueous and membrane solvation models for protein simulations are also described. Finally, we summarize recent progress in protein structure refinement using new force fields. PMID- 22323220 TI - A practical introduction to molecular dynamics simulations: applications to homology modeling. AB - In this chapter, practical concepts and guidelines are provided for the use of molecular dynamics (MD) simulation for the refinement of homology models. First, an overview of the history and a theoretical background of MD are given. Literature examples of successful MD refinement of homology models are reviewed before selecting the Cytochrome P450 2J2 structure as a case study. We describe the setup of a system for classical MD simulation in a detailed stepwise fashion and how to perform the refinement described in the publication of Li et al. (Proteins 71:938-949, 2008). This tutorial is based on version 11 of the AMBER Molecular Dynamics software package (http://ambermd.org/). However, the approach discussed is equally applicable to any condensed phase MD simulation environment. PMID- 22323219 TI - Automated protein structure modeling with SWISS-MODEL Workspace and the Protein Model Portal. AB - Comparative protein structure modeling is a computational approach to build three dimensional structural models for proteins using experimental structures of related protein family members as templates. Regular blind assessments of modeling accuracy have demonstrated that comparative protein structure modeling is currently the most reliable technique to model protein structures. Homology models are often sufficiently accurate to substitute for experimental structures in a wide variety of applications. Since the usefulness of a model for specific application is determined by its accuracy, model quality estimation is an essential component of protein structure prediction. Comparative protein modeling has become a routine approach in many areas of life science research since fully automated modeling systems allow also nonexperts to build reliable models. In this chapter, we describe practical approaches for automated protein structure modeling with SWISS-MODEL Workspace and the Protein Model Portal. PMID- 22323221 TI - Methods for accurate homology modeling by global optimization. AB - High accuracy protein modeling from its sequence information is an important step toward revealing the sequence-structure-function relationship of proteins and nowadays it becomes increasingly more useful for practical purposes such as in drug discovery and in protein design. We have developed a protocol for protein structure prediction that can generate highly accurate protein models in terms of backbone structure, side-chain orientation, hydrogen bonding, and binding sites of ligands. To obtain accurate protein models, we have combined a powerful global optimization method with traditional homology modeling procedures such as multiple sequence alignment, chain building, and side-chain remodeling. We have built a series of specific score functions for these steps, and optimized them by utilizing conformational space annealing, which is one of the most successful combinatorial optimization algorithms currently available. PMID- 22323222 TI - Ligand-guided receptor optimization. AB - Receptor models generated by homology or even obtained by crystallography often have their binding pockets suboptimal for ligand docking and virtual screening applications due to insufficient accuracy or induced fit bias. Knowledge of previously discovered receptor ligands provides key information that can be used for improving docking and screening performance of the receptor. Here, we present a comprehensive ligand-guided receptor optimization (LiBERO) algorithm that exploits ligand information for selecting the best performing protein models from an ensemble. The energetically feasible protein conformers are generated through normal mode analysis and Monte Carlo conformational sampling. The algorithm allows iteration of the conformer generation and selection steps until convergence of a specially developed fitness function which quantifies the conformer's ability to select known ligands from decoys in a small-scale virtual screening test. Because of the requirement for a large number of computationally intensive docking calculations, the automated algorithm has been implemented to use Linux clusters allowing easy parallel scaling. Here, we will discuss the setup of LiBERO calculations, selection of parameters, and a range of possible uses of the algorithm which has already proven itself in several practical applications to binding pocket optimization and prospective virtual ligand screening. PMID- 22323223 TI - Loop simulations. AB - Loop modeling is crucial for high-quality homology model construction outside conserved secondary structure elements. Dozens of loop modeling protocols involving a range of database and ab initio search algorithms and a variety of scoring functions have been proposed. Knowledge-based loop modeling methods are very fast and some can successfully and reliably predict loops up to about eight residues long. Several recent ab initio loop simulation methods can be used to construct accurate models of loops up to 12-13 residues long, albeit at a substantial computational cost. Major current challenges are the simulations of loops longer than 12-13 residues, the modeling of multiple interacting flexible loops, and the sensitivity of the loop predictions to the accuracy of the loop environment. PMID- 22323224 TI - Methods of protein structure comparison. AB - Despite its apparent simplicity, the problem of quantifying the differences between two structures of the same protein or complex is nontrivial and continues evolving. In this chapter, we described several methods routinely used to compare computational models to experimental answers in several modeling assessments. The two major classes of measures, positional distance-based and contact-based, are presented, compared, and analyzed. The most popular measure of the first class, the global RMSD, is shown to be the least representative of the degree of structural similarity because it is dominated by the largest error. Several distance-dependent algorithms designed to attenuate the drawbacks of RMSD are described. Measures of the second class, contact-based, are shown to be more robust and relevant. We also illustrate the importance of using combined measures, utility-based measures, and the role of the distributions derived from the pairs of experimental structures in interpreting the results. PMID- 22323225 TI - Homology modeling of class a G protein-coupled receptors. AB - G protein-coupled receptors (GPCRs) are a large superfamily of membrane bound signaling proteins that hold great pharmaceutical interest. Since experimentally elucidated structures are available only for a very limited number of receptors, homology modeling has become a widespread technique for the construction of GPCR models intended to study the structure-function relationships of the receptors and aid the discovery and development of ligands capable of modulating their activity. Through this chapter, various aspects involved in the constructions of homology models of the serpentine domain of the largest class of GPCRs, known as class A or rhodopsin family, are illustrated. In particular, the chapter provides suggestions, guidelines, and critical thoughts on some of the most crucial aspect of GPCR modeling, including: collection of candidate templates and a structure based alignment of their sequences; identification and alignment of the transmembrane helices of the query receptor to the corresponding domains of the candidate templates; selection of one or more templates receptor; election of homology or de novo modeling for the construction of specific extracellular and intracellular domains; construction of the 3D models, with special consideration to extracellular regions, disulfide bridges, and interhelical cavity; validation of the models through controlled virtual screening experiments. PMID- 22323226 TI - Homology modeling of transporter proteins (carriers and ion channels). AB - Transporter proteins are divided into channels and carriers and constitute families of membrane proteins of physiological and pharmacological importance. These proteins are targeted by several currently prescribed drugs, and they have a large potential as targets for new drug development. Ion channels and carriers are difficult to express and purify in amounts for X-ray crystallography and nuclear magnetic resonance (NMR) studies, and few carrier and ion channel structures are deposited in the PDB database. The scarcity of atomic resolution 3D structures of carriers and channels is a problem for understanding their molecular mechanisms of action and for designing new compounds with therapeutic potentials. The homology modeling approach is a valuable approach for obtaining structural information about carriers and ion channels when no crystal structure of the protein of interest is available. In this chapter, computational approaches for constructing homology models of carriers and transporters are reviewed. PMID- 22323227 TI - Methods for the homology modeling of antibody variable regions. AB - Antibodies are one of the critical molecules of our immune system and are unique in their enormous diversity required for recognizing various antigens. Antibodies are protein molecules and their antigen interacting region, the fragment variable (F (V)), is typically composed of a light (V (L)) and heavy (V (H)) chain. In particular, three loops each at the tip of the V (L) and the V (H), known as the complementarity determining region (CDR) loops, are responsible for binding to the antigen. While the framework regions of the V (L) and V (H) are relatively constant across the entire repertoire of antibodies, the conformation of the CDR loops varies extensively to enable the antibody to recognize different antigens. Three-dimensional structures of antibodies illustrating the V (L)-V (H) relative orientation and the CDR conformations are needed to gain insight into antibody stability, immunogenicity, and antibody-antigen interactions. Computational modeling provides a fast and inexpensive route for generating antibody structural models. This chapter highlights the various features crucial for creating a successful antibody homology model. PMID- 22323228 TI - Investigating protein variants using structural calculation techniques. AB - Structure calculation techniques can be very useful to bridge the gap between available sequence information and structural knowledge. In order to understand the molecular mechanisms behind diseases caused by residue exchanges, knowledge about the modified structure is needed. In this chapter, we describe how energy minimizations and molecular dynamics can be useful tools in order to study the structural effects of sequence variation. With these techniques, together with investigation of other properties, it is often possible to obtain a complete picture of the effect and mechanism behind disease-causing mutations. To take this information one step further, we also describe prediction methods that can be used to judge the effects of mutations and how to evaluate these and the interplay between the protein properties. PMID- 22323229 TI - Macromolecular assembly structures by comparative modeling and electron microscopy. AB - Advances in electron microscopy allow for structure determination of large biological machines at increasingly higher resolutions. A key step in this process is fitting component structures into the electron microscopy-derived density map of their assembly. Comparative modeling can contribute by providing atomic models of the components, via fold assignment, sequence-structure alignment, model building, and model assessment. All four stages of comparative modeling can also benefit from consideration of the density map. In this chapter, we describe numerous types of modeling problems restrained by a density map and available protocols for finding solutions. In particular, we provide detailed instructions for density map-guided modeling using the Integrative Modeling Platform (IMP), MODELLER, and UCSF Chimera. PMID- 22323230 TI - Preparation and refinement of model protein-ligand complexes. AB - The formation of ligand-protein complexes are critical for the correct functioning of a cell. The prediction of these interactions is important for our understanding of how the cell works and for the development of new drug molecules. Homology modeling is a method for predicting the structure of a protein based on a crystal structure template. Once a model of the protein is complete, a ligand-docking algorithm predicts the ligand-protein model interaction by searching for the best steric and energetically favorable fit. A refinement of the ligand-binding pocket improves the predicted interactions by considering the flexible nature of the ligand-binding pocket. In this chapter, we describe, from first principles, methods to identify and prepare the ligand binding pocket in a protein model, to dock the ligand, and refine the resulting complex. PMID- 22323231 TI - Modeling peptide-protein interactions. AB - Peptide-protein interactions are prevalent in the living cell and form a key component of the overall protein-protein interaction network. These interactions are drawing increasing interest due to their part in signaling and regulation, and are thus attractive targets for computational structural modeling. Here we report an overview of current techniques for the high resolution modeling of peptide-protein complexes. We dissect this complicated challenge into several smaller subproblems, namely: modeling the receptor protein, predicting the peptide binding site, sampling an initial peptide backbone conformation and the final refinement of the peptide within the receptor binding site. For each of these conceptual stages, we present available tools, approaches, and their reported performance. We summarize with an illustrative example of this process, highlighting the success and current challenges still facing the automated blind modeling of peptide-protein interactions. We believe that the upcoming years will see considerable progress in our ability to create accurate models of peptide protein interactions, with applications in binding-specificity prediction, rational design of peptide-mediated interactions and the usage of peptides as therapeutic agents. PMID- 22323232 TI - Comparison of common homology modeling algorithms: application of user-defined alignments. AB - The number of known three-dimensional protein sequences is orders of magnitude higher than the number of known protein structures. This is a result of an increase in large-scale genomic sequencing projects, the inability of proteins to crystallize or crystals to diffract well, or a simple lack of resources. An alternative is to use one of a variety of available homology modeling programs to produce a computational model of a protein. Protein models are produced using information from known protein structures found to be similar. Here, we compare the ability of a number of popular homology modeling programs to produce quality models from user-defined target-template sequence alignments over a range of circumstances including low sequence identity, variable sequence length, and when interfaced with a protein or small molecule. Programs evaluated include Prime, SWISS-MODEL, MOE, MODELLER, ROSETTA, Composer, ORCHESTRAR, and I-TASSER. Proteins to be modeled were chosen to test a range of sequence identities, sequence lengths, and protein motifs and all are of scientific importance. These include HIV-1 protease, kinases, dihydrofolate reductase, a viral capsid protein, and factor Xa among others. For the most part, the programs produce results that are similar. For example, all programs are able to produce reasonable models when sequence identities are >30% and all programs have difficulties producing complete models when sequence identities are lower. However, certain programs fare slightly better than others in certain situations and we attempt to provide insight on this topic. PMID- 22323233 TI - Hospitals, finance, and health system reform in Britain and the United States, c. 1910-1950: historical revisionism and cross-national comparison. AB - Comparative histories of health system development have been variously influenced by the theoretical approaches of historical institutionalism, political pluralism, and labor mobilization. Britain and the United States have figured significantly in this literature because of their very different trajectories. This article explores the implications of recent research on hospital history in the two countries for existing historiographies, particularly the coming of the National Health Service in Britain. It argues that the two hospital systems initially developed in broadly similar ways, despite the very different outcomes in the 1940s. Thus, applying the conceptual tools used to explain the U.S. trajectory can deepen appreciation of events in Britain. Attention focuses particularly on working-class hospital contributory schemes and their implications for finance, governance, and participation; these are then compared with Blue Cross and U.S. hospital prepayment. While acknowledging the importance of path dependence in shaping attitudes of British bureaucrats toward these schemes, analysis emphasizes their failure in pressure group politics, in contrast to the United States. In both countries labor was also crucial, in the United States sustaining employment-based prepayment and in Britain broadly supporting system reform. PMID- 22323234 TI - Perceptions of the health system and public trust in government in low- and middle-income countries: evidence from the World Health Surveys. AB - In low- and middle-income countries, health care systems are an important means by which individuals interact with their government. As such, aspects of health systems in these countries may be associated with public trust in government. Greater trust in government may in turn improve governance and government effectiveness. We identify health system and non-health system factors hypothesized to be associated with trust in government and fit several multilevel regression models to cross-national data from 51,300 respondents in thirty-eight low- and middle-income countries participating in the World Health Surveys. We find that health system performance factors are associated with trust in government while controlling for a range of non-health system covariates. Taken together, higher technical quality of health services, more responsive service delivery, fair treatment, better health outcomes, and financial risk protection accounted for a 13 percentage point increase in the probability of having trust in government. Health system performance and good governance may be more inter related than previously thought. This finding is particularly important for low income and fragile states, where health systems and governments tend to be weakest. Future research efforts should focus on determining the causal mechanisms that underlie the observed associations between health system performance and trust in government. PMID- 22323235 TI - A window of opportunity: the Louisiana Birth Outcomes Initiative. AB - Louisiana ranks forty-ninth nationally in birth outcomes indicators such as infant mortality and in the percentage of low birth weight and very low birth weight babies. This article describes the formation of the Birth Outcomes Initiative, a statewide targeted investment to reduce poor birth outcomes. It describes how the initiative is a result of the convergence of the triad of well defined problems, a credible array of potential solutions, and favorable political process. It then describes the Birth Outcomes Initiative in Louisiana, a targeted program to improve health indicators for reproductive-aged women and reduce the incidence of prematurity, low birth weight, and infant mortality. PMID- 22323236 TI - Improving direct-care compensation in nursing homes: Medicaid wage pass-through adoption, 1999-2004. AB - Because states play such a prominent role in the U.S. health care system, they have long grappled with how to best control health care costs while maintaining high quality of care. There are many policy tools available to address efficiency and quality concerns--from pure state regulation to market-oriented competition designs. Given public discourse and official party platforms, one would assume that states controlled by Democrats would be more likely to adopt regulatory reforms. This study examines whether party control, as well as other economic and political factors, is associated with adopting wage pass-through (WPT) policies, which direct a portion of Medicaid reimbursement or its increase toward nursing home staff in an effort to reduce staff turnover, thereby increasing efficiency and the quality of care provided. Contrary to expectations, results indicate that states with Republican governors were against WPT adoption only when for-profit industry pressure increased; otherwise, they were more likely to favor adoption than their Democratic counterparts. This suggests a more complex relationship between partisanship and state-level policy adoption than is typically assumed. Results also indicate that state officials reacted predictably to prevailing political and economic conditions affecting state fiscal-year decisions but required sufficient governing capacity to successfully integrate WPTs into existing reimbursement system arrangements. This suggests that WPTs represent a hybrid between comprehensive and incremental policy change. PMID- 22323237 TI - Issue ads and the health reform debate. AB - The public debate over health care reform in 2009 was carried out partly through issue advertisements aired online and on television. Did these advertisements alter the course of the debate over health care reform? While millions of dollars are spent each year on issue ads, little is known about their effects. Results from a naturalistic online experiment on the effects of issue ads suggest that they can influence the perceived importance of an issue and perceptions of politicians associated with the featured policy while influencing policy support only among those low in political awareness. PMID- 22323238 TI - Negotiating authority: a comparative study of reform in medical training regimes. AB - Recently the medical profession has faced increased outside pressure to reform postgraduate medical training programs to better equip young doctors for changing health care needs and public expectations. In this article we explore the impact of reform on professional self-governance by conducting a comparative historical institutional analysis of postgraduate medical training reform in the United Kingdom and the Netherlands. In both countries the medical training regime has shifted from professional self-regulation to coregulation. Yet there are notable differences in each country that cannot be explained solely by diverging institutional contexts. They also result from the strategic actions by the actors involved. Based on an assessment of the recent literature on institutional transformation, this article shows how strategic actions set negotiating authority processes into motion, producing new and sometimes surprising institutional arrangements that can have profound effects on the distribution and allocation of authority in the medical training regime. It stresses the need to study the interactions among political context, the properties of institutions, and negotiating authority processes, as they are crucially important to understanding institutional transformation. PMID- 22323239 TI - In vitro degradation and cytocompatibility of dicalcium phosphate dihydrate cements prepared using the monocalcium phosphate monohydrate/hydroxyapatite system reveals rapid conversion to HA as a key mechanism. AB - We previously showed that dicalcium phosphate dihydrate (DCPD) cements can be prepared using monocalcium phosphate monohydrate (MCPM) and hydroxyapatite (HA). In this study, we have characterized the degradation properties and biocompatibility of these novel cements. To study the degradation properties, cements were prepared using MCPM:HA molar ratios of 4:1, 2:1, 2:3, and 2:5. Degradation was evaluated in vitro by static soaking in PBS, and changes in pH, mass, compressive strength, and composition were monitored. Conversion of DCPD to HA was noted in the 4:1 group, which initially consisted of pure DCPD. However, the 2:1 group, which initially consisted of DCPD and an intermediate amount of unreacted HA, underwent rapid conversion to HA associated with significantly greater pH drop and mass loss as well as a complete loss of mechanical integrity. On the basis of these results, we directly compared the cytocompatibility of 2:1 MCPM:HA cements to DCPD cements prepared with an equivalent percent molar excess of beta-tricalcium phosphate (beta-TCP) using an in vitro cell viability assay. Viability of cells co-cultured with 2:1 MCPM:HA cements was significantly reduced after just 48 h, while viability of cells cultured with the beta-TCP-based cements was no different from control cells. In conclusion, this study demonstrates that conversion to HA plays an important role in the degradation of DCPD cements prepared with the MCPM/HA system, affecting both physical properties and cytocompatibility. These results could have important clinical implications for MCPM/HA cements. PMID- 22323241 TI - Hypervalent octahedral SiH6(2-) species from high-pressure synthesis. PMID- 22323240 TI - Effect of legume grains as a source of dietary protein on the quality of organic lamb meat. AB - BACKGROUND: This study evaluated the effects on lamb growth, carcass traits and meat quality of replacing conventional soybean meal in the diet with alternative legume grains. RESULTS: Twenty-eight male lambs of Comisana breed weighing 16.9 +/- 2.7 kg at weaning (66 +/- 6 days old) were assigned to one of four diets. Until slaughter at 129 +/- 6 days of age, each group received ad libitum pelleted alfalfa hay and concentrates differing in the source of protein: chickpea, faba bean, pea or soybean meal. Lambs fed chickpea showed higher dry matter and protein intakes from concentrate than those fed soybean. Lambs' growth, carcass weight and net dressing percentage did not vary by protein source, although chickpea lambs had more perirenal and pelvic fat than those in the soybean group. Diet did not affect chemical composition, colour, thawing and cooking losses, tenderness, and sensory properties of meat. Chickpea increased trans-vaccenic and linoleic acid, and chickpea and faba bean increased the isomers of conjugated linoleic acid. CONCLUSIONS: Legume grains can completely replace soybean meal in concentrate, resulting in lamb carcasses and meat of comparable quality. Chickpea leads to an increase in feed intake of lambs and in fat depots in the carcass, and a more beneficial fatty acid profile. PMID- 22323242 TI - Measurement of heritability of myocardial blood flow by positron emission tomography: the Twins Heart Study. AB - OBJECTIVE: To estimate the heritability of myocardial blood flow (MBF) and coronary flow reserve (CFR) measured with positron emission tomography (PET). DESIGN: Cross-sectional twin study. SETTING: General clinical research centre of a university hospital at Atlanta, USA. PATIENTS: A sample of 180 middle-aged (mean+/-SD 55+/-2.9 years) male twins, including 107 monozygotic and 73 dizygotic twins. MAIN OUTCOME MEASURES: All twins underwent imaging of MBF with PET (13)NH(3) at rest and after adenosine stress during a single imaging session. Structural equation modelling was used to estimate the heritability of MBF at rest and during adenosine stress, as well as of CFR. RESULTS: The basal MBF (mean+/-SD) was 0.69+/-0.20 ml/min/g, and the MBF during adenosine stress was 1.70+/-0.49 ml/min/g; the CFR was 2.62+/-0.99. There was substantial heritability for MBF both at rest (0.48, 95% CI 0.29 to 0.64) and during adenosine stress (0.51, 95% CI 0.29 to 0.68), as well as CFR (0.48, 95% CI 0.26 to 0.65). CONCLUSIONS: For the first time, a substantial genetic contribution to the interindividual variation in MBF and CFR measured with PET in middle-aged men has been demonstrated. The data suggest that a fruitful direction for future work would be the identification of genetic variants for early atherosclerotic stages assessed by PET imaging. PMID- 22323243 TI - Self-assembled flexible microlasers. AB - Hemispherical microresonators with tunable sizes are obtained based on the hydrophobic effect on distributed Bragg reflectors. Under optical excitation, whispering gallery mode lasing is observed from the dye-doped microresonators at room temperature. The results indicate the potential application of the flexible microresonators in photonic integrated circuits. PMID- 22323244 TI - A potential drug-herbal interaction between Ginkgo biloba and efavirenz. AB - Efavirenz (EFV) is primarily metabolized by cytochrome P450 (CYP) 2B6 and to a lesser extent by CYP3A4. Drugs that significantly inhibit or induce these enzymes would then be expected to increase or lower the levels of EFV potentially resulting in toxicity or therapeutic failure, respectively. The constituents of Ginkgo biloba extract have been demonstrated to induce gene expression of the CYP450 enzymes. We report a case in which a potential drug-herb interaction may have led to virological breakthrough in a patient that was maintained on the same regimen for 10 years. Therefore, a drug-herbal interaction may be expected when these agents are taken concurrently, and we advise clinicians to avoid this combination when possible. PMID- 22323245 TI - A comparative study of oral candidal carriage and its association with CD4 count between HIV-positive and healthy individuals. AB - AIMS AND OBJECTIVES: To correlate asymptomatic oral candidal carriage in HIV positive patients and normal individuals and determine its association with CD4 count. MATERIAL AND METHODS: Forty HIV-positive patients and forty healthy individuals were included in this study. Saliva from both groups was collected by the spitting method. The saliva from each individual was incubated aerobically on Sabouraud Dextrose agar with antibiotics at 37 degrees C. The germ tube method was used for differentiation of candidal species, whether the Candida albicans or non-Candida albicans. Surface count method was used to count the number of colonies of candida species. Data were analyzed by chi square and Mann-Whitney test. RESULTS: Oral candidal carriage was found in 22 out of 40 (55%) HIV positive patients. In healthy volunteers, oral candidal carriage was found in 6 out of 40 (15%) individuals (p value = 0.0002), which is significantly higher. Similarly, density carriage in the HIV-positive patients was found to be significantly higher than that in the HIV-negative group (p value = 0.002). However, oral yeast carriage was not associated with CD4 count (correlation coefficient r = -0.087). CONCLUSION: Within the limits of the study, we concluded oral candidal carriage rate and density carriage higher in HIV-positive patients than in healthy individuals. PMID- 22323246 TI - Effects of trabeculectomy on posture-induced intraocular pressure changes over time. AB - INTRODUCTION: To determine whether trabeculectomy affects postural-induced changes in intraocular pressure (IOP), and whether it is maintained. METHODS: Thirty-six eyes of 36 patients with open-angle glaucoma who were scheduled for their initial trabeculectomy with adjunctive mitomycin C were prospectively examined. The IOP was measured in the sitting and the lateral decubitus position with an ICare rebound tonometer before, and 1, 3, and 12 months after trabeculectomy. RESULTS: Twenty-nine eyes of 29 patients completed this study. The mean baseline IOP measured with the ICare tonometer was 17.4 +/- 4.9 mmHg in the sitting position and 21.3 +/- 5.6 mmHg in the lateral decubitus position (p < 0.001). This postural IOP difference, +3.9 mmHg, was reduced to +1.3 +/- 1.7 mmHg at 1 month and to +0.8 +/- 1.5 mmHg at 3 months after the trabeculectomy (p < 0.001 and p = 0.004 respectively). This decrease in the degree of posture dependent IOP change was maintained at +1.7 +/- 2.2 mmHg at 1 year postoperatively (p < 0.001). In three cases, the postural IOP changes returned to the baseline level, and all three had a failed bleb. CONCLUSIONS: Our results indicate that trabeculectomy not only reduces the IOP but also reduces the degree of posture-induced changes in the IOP. Our findings also speculate that measuring the postural IOP changes after trabeculectomy might provide a clue on the functioning of a filtering bleb. PMID- 22323247 TI - Rare-earth-transition-metal organic-inorganic hybrids based on Keggin-type polyoxometalates and pyrazine-2,3-dicarboxylate. AB - Five rare-earth-transition-metal (RE-TM) heterometal organic-inorganic hybrids based on Keggin-type silicotungstates and mixed ligands H2pzda (pzda=pyrazine-2,3 dicarboxylate) and en (en=ethylenediamine) (enH2)[Cu(en)2(H2O)]2{[Cu(en)2][Cu(en)2(H2O)][(alpha-SiW11 O39)RE(H2O)(pzda)]}2.n H2O (n~4; RE=YIII (1), DyIII (2), YbIII (3), and LuIII (4)) and [Cu(en)2(H2O)]2{[Cu(en)2]2[Cu(pzda)2][(alpha-H2SiW11O39)Ce(H2O)]2}.n H2O (5; n~8) have been hydrothermally synthesized and structurally characterized. Compounds 1 5 all contain the dimeric mono-RE substituted Keggin [RE(alpha-SiW11O39)]210- subunits linked by H2pzda ligands. Interestingly, 1-4 exhibit discrete structures, in which the H2pzda ligand acts as a tetradentate ligand to bind the RE and Cu cations, whereas 5 displays a 1D double-chain architecture, in which the H2pzda ligand adopts a new pentadentate mode to connect the Ce and Cu cations. To our knowledge, 1-5 represent the first monovacant Keggin-type silicotungstates containing both RE-TM heterometals and mixed ligands. The luminescence of 2 is derived from the combination of the DyIII cations and H2pzda ligands, whereas the luminescence properties of 1 and 3-5 are attributable to the H2pzda ligands. PMID- 22323248 TI - Imaging the inhibition by anti-beta1 integrin antibody of lung seeding of single osteosarcoma cells in live mice. AB - Integrins play a role in tumor growth and metastasis. However, the effect of integrin inhibition has not been visualized on single cancer cells in vivo. In this study, we used a powerful subcellular in vivo imaging model to demonstrate how an anti-integrin antibody affects seeding and growth of osteosarcoma cells on the lung. The 143B human osteosarcoma cell line, expressing red fluorescent protein (RFP) in the cytoplasm and green fluorescent protein (GFP) in the nucleus, was established. Such double-labeled cells enable imaging of apoptosis and mitosis and other nuclear-cytoplasmic dynamics. Using the double-labeled osteosarcoma cells, single cancer-cell seeding in the lung after i.v. injection of osteosarcoma cells was imaged. The anti-beta1 integrin monoclonal antibody, AIIB2, greatly inhibited the seeding of cancer cells on the lung (experimental metastasis) while a control antibody had no effect. To image the efficacy of the anti-integrin antibody on spontaneous metastasis, mice with orthotopically growing 143B-RFP cells in the tibia were also treated with AIIB2 or control anti rat IgG1 antibody. After 3 weeks treatment, mice were sacrificed and primary tumors and lung metastases were evaluated with fluorescence imaging. AIIB2 significantly inhibited spontaneous lung metastasis but not primary tumor growth, possibly due to inhibition of lung seeding of the cancer cells as imaged in the experimental metastasis study. AIIB2 treatment also increased survival of mice with orthotopically growing 143B-RFP. PMID- 22323249 TI - The many molecular mysteries of melanoma. AB - Melanoma of the skin is one of the most rapidly increasing malignancies in both young and old patients (1,2). Not only is the incidence increasing, but the number of annual deaths from melanoma is also on the rise worldwide (3). In the United States, melanoma will be diagnosed in 43,000 new patients each year and be responsible for 7300 deaths (1 death every 72 min). The capacity of melanoma to develop in young patients is reflected by the rather alarming statistic that it has become one of the top causes of death in both men and women between the ages of 25 and 40 (3). Indeed, among Caucasian females, melanoma is the leading cause of death from malignancy between the ages of 25 and 29 (3). It is expected that by 2002, 1 in 70 Americans will develop melanoma during their lifetime (2). Also, melanoma is second only to adult leukemia as the leader in the number of potential years of life lost, which is significantly greater than for patients with cervical, breast, and colon malignancies (4). Despite the frequent presence of melanoma and major associated health problems around the globe, only recently have clinicians and laboratory-based researchers begun to unravel some of the molecular mysteries of melanoma (5,6). The purpose of Melanoma: Methods and Protocols, published as part of the Methods in Molecular MedicineTM series, is to provide an up-to-date review of the many advances that have taken place during the past several years involving the pathophysiology, diagnosis, genetic analysis, and treatment approaches for patients with melanoma (7). PMID- 22323250 TI - Isolation of tumor suppressor genes in melanoma by cDNA microarray. AB - The multistep genetic alterations thought to involve both oncogenes and tumor suppressor genes that are causally related to melanocytic transformation remain largely undetermined (1). Mapping of alterations to chromosome 6 indicates that multiple genetic loci on 6q contribute causally to the development and progression of malignant melanoma (1). This notion is also supported by the introduction of chromosome 6 in malignant melanoma cell lines suppressing either their tumorigenicity (2) or metastasis (3,4). However, the suppressor genes involved have yet to be identified. PMID- 22323251 TI - Molecular characterization of melanoma-derived antigens. AB - In the last decade, many antigens expressed by tumors and recognized by the immune system have been identified. Melanoma was among the first tumors found to express such tumor-associated antigens, and, therefore, melanoma is currently one of the best and extensively studied tumors for which new techniques have been introduced to optimize the characterization of tumor antigens. In this chapter, we discuss the techniques used for identification of melanoma-expressed antigens recognized by cytotoxic T-lymphocytes (CTLs). In more detail, we describe in Subheading 3. the reverse immunology method. PMID- 22323252 TI - Experimental induction of human atypical melanocytic lesions and melanoma in ultraviolet-irradiated human skin grafted to immunodeficient mice. AB - The development of melanoma and its precursor lesions has been associated with intense intermittent sun exposure and the deleterious effects of ultraviolet (UV) light (1). This is supported by epidemiologic data as well as several animal models in which melanoma could be induced or promoted by UV irradiation (Table 1). It remains to be elucidated what changes UV light induces in the human pigment cells at the molecular level that trigger malignant transformation. Experimental animal models established to date have helped us to understand the etiology and pathobiology of melanoma, but they do not necessarily mirror the biology of human melanoma development. The skin morphology in animals differs substantially from that in humans, and melanocytes show a different distribution pattern. In mice, melanocytes are mainly located in the hair follicles, whereas in humans, melanocytes are found epidermally at the basement membrane zone. The number of cell layers of the epidermis is, for the most part, markedly less in mice than in humans (Fig. 1). PMID- 22323253 TI - Dissection of immunosuppressive effects of ultraviolet radiation. AB - For nearly 100 yr physicians and scientists have appreciated the carcinogenic potential of the ultraviolet (UV) radiation present in sunlight 0(1,2). During the latter part of the twentieth century, immunologists and dermatologists realized that UV radiation suppressed the immune response (3-5). Moreover, the immune suppression induced by UV radiation is a major risk factor for the induction of nonmelanoma skin cancer (6). The association between nonmelanoma skin cancer induction and immune suppression has fueled the efforts of many to study the immunologic mechanism underlying UV-induced immune suppression. This chapter focuses on describing the methods used to dissect the suppressive effects of UV on the immune system, concentrating particularly on in vivo models of immunity. PMID- 22323254 TI - Antisense oligonucleotides as research tools. AB - The use of antisense oligonucleotides as both research tools and therapeutic molecules has emerged as a powerful alternative to small molecule inhibitors. Antisense oligonucleotides are short pieces of chemically modified DNA designed to hybridize to specific mRNA sequences present in the target gene. The oligonucleotide interaction with the targeted mRNA can lead to inhibition in the translation of the protein encoded by the targeted transcript through a variety of reasonably well-characterized mechanisms (1-3). PMID- 22323255 TI - Genetic Testing in Familial Melanoma : Epidemiologic/Genetic Assessment of Risks and Role of CDKN2A Analysis. AB - The first description of familial melanoma in the English literature appeared in 1820, when Norris (1) reported: It is remarkable that this gentleman's father, about thirty years ago, died of a similar disease.... This tumour, I have remarked, originated in a mole, and it is worth mentioning, that not only my patient and his children had many moles on various parts of their bodies, but also his own father and brothers had many of them.... These facts, together with a case that has come under my notice, rather similar, would incline me to believe that this disease is hereditary. Since then, many families with a predisposition to melanoma have been described worldwide (2-5). For purposes of case definition, our laboratory curently defines familial melanoma (FMM) as a family containing >2 affected first-degree relatives with melanoma and/or pancreatic carcinoma. According to this definition, about 8-12% of melanoma is inherited as an autosomal dominant trait with variable penetrance. Affected members (AFM) of these FMM kindreds may develop multiple primary melanoma (6) and/or pancreatic cancer (7) and typically present at an earlier age than do patients with sporadic disease. In a subset of such individuals and kindreds, germline mutations of the CDKN2A gene (also known as p16INK4A and MTS1) cosegregate with cases of melanoma (2-5).We have hypothesized that the identification of mutation carriers may in the future allow us to direct resources to the prevention and surveillance of mela noma in high-risk individuals and families. This chapter provides an overview of melanoma genetics, as well as the indications, drawbacks, and methods of germline CDKN2A mutation screening by polymerase chain reaction (PCR) amplification and automated sequencing of genomic DNA. PMID- 22323256 TI - Role of molecular biology in diagnostic pathology of melanoma. AB - Cutaneous melanoma is the most rapidly increasing malignancy in the white European population; its clinical significance is enhanced because it can affect younger individuals (1-3). The high mortality rate among melanoma patients, second to lung cancer, is related to melanoma's resistance to therapy once the metastastic process has started (4-6). The tumor derives from epidermal melanocytes, either activated or genetically altered; thus, important precursors include activated melanocytes present within solar lentigo or forming prema- lignant lesions such as lentigo maligna (7-10). Melanoma can also arise from relatively benign or atypical nevomelanocyte lesions (7-10). Benign lesions that can nevertheless result in melanoma include congenital melanocytic nevus, nevus of Ota, nevus of Ito, and cellular blue nevus. The atypical lesions with the same possible outcome are represented by acquired dysplastic melanocytic nevus, melanocytic dysplasia on the acral or mucosal surface, spindle cell and/or atypical epithelioid melanocytic nevus (Spitz nevus), and dysplastic and/or congenital nevus spilus (7-10). PMID- 22323257 TI - Identification of altered gene expression associated with pigmentary lesions by differential display analysis. AB - Identification of alterations in gene expression is an important step in understanding the development and progression of human disease. For pigmentary disorders with an unresolved hereditary component, genetic and epigenetic changes that alter the expression of genes as a direct or indirect consequence can be investigated by expression analysis. This can be of particular importance in conditions in which multiple genes are involved, as in melanoma or vitiligo (1,2). Differential display analysis is a technique that is widely used and entails semiquantitative polymerase chain reaction (PCR) amplification of 3' ends of messenger RNA (mRNA) (3- 6). The primer sets used hybridize to the poly-A tail of mRNA on one end, and to an arbitrary countersequence on the other. Each set of primers is designed to amplify some 150 messages present in the RNA under study. These messages are subsequently separated by polyacrylamide gel electrophoresis. Using a labeled nucleotide in the PCR reaction, the intensity of each band can subsequently be compared in samples of interest. Following reamplification, confirmation, cloning, and sequencing, the fragments of interest are further analyzed. Figure 1 outlines this sequence of events. Although the length of the fragments amplified usually excludes coding regions, the 3' noncoding regions are unique and can serve to identify the gene of interest, provided the fragment belongs to a gene or an expressed sequence tag (EST) that has previously been submitted to GenBank (7). PMID- 22323258 TI - Fluorescence in situ hybridization as a tool in molecular diagnostics of melanoma. AB - Structural and numerical chromosomal abnormalities have been observed in all types of malignancies. These events are associated with neoplastic pathogenesis and progression (1). For a long time, conventional cytogenetics analysis was the prevalent approach in assessing chromosomal rearrangements. Many data were collected initially from hematologic malignancies because of ease of analysis, despite the fact that they represent only 10% of all malignancies (2). Cytogenetic data on solid tumors were hampered by the technical difficulties in obtaining dividing malignant cells. During the last two decades, these problems were solved and data have been quickly acquired. Karyotyping of malignant melanoma cell lines reveals more than 95% of the cases presenting aneuploidy (numerical chromosome abnormalities: near triploidy) (3), and all the cell lines present structural abnormalities (balanced and unbalanced translocations, inversions and deletions) (see, e.g., German Collection of Microorganisms and Cell Cultures [Dr. H. Drexler] at http://www.dsmz.de (4,5). Cytogenetic analysis of malignant melanoma cells allowed the identification of nonrandom karyotypic changes involving chromosomes 1, 6, and 7 and, to some extent, chromosomes 9 and 10. PMID- 22323259 TI - Antigen-pulsed dendritic cell approach to melanoma. AB - Dendritic cells (DCs) are potent antigen-presenting cells (1) with wide tissue distribution. They are classified based primarily on their localization: as Langerhans cells when present in the epidermis and as dermal DCs when found in the dermis. DCs exhibit several common features: an irregular shape with elongated dendritic processes, a distinctive cell-surface phenotype, low buoyant density, active motility, and the ability to stimulate vigorous proliferation of unprimed T-cells. DCs are able to ingest, process, and present antigen in the context of major histocompatibility complex (MHC) molecules. However, because of their high expression of MHC class I and II, as well as costimulatory molecules and adhesion molecules, DCs have the ability to induce primary T-cell-dependent immune responses in vivo and in vitro. This outstanding feature gives DCs a central role in controlling adaptive T-cell-based immunity. PMID- 22323260 TI - Gene therapy in melanoma. AB - The identification of genes involved in different biologic functions and in the pathogenesis of diseases has paved the way to the possibility of either interfering with the role of such genes or replacing them in somatic cells in case of loss, which may occur in some genetic diseases or cancer. Such progress has been accomplished thanks to advances in molecular biology and applied technology that allow the transport and insertion of genes into recipient cells by viral or physical vectors as well as the inhibition of gene transcription by antisense oligonucleotides. Methods have also been devised to transfer genes not only in vitro but also in vivo, although this latter approach is still limited owing to poor selectivity and targeting of most vectors when given systemically. Viral and physical vectors have been employed; each of these vectors has distinct advantages and disadvantages, and, therefore, the appropriate vector should be selected according to the therapeutic system involved (1). Retro viral vectors have been used largely for their ability to selectively transfect proliferating cells, a feature that can be advantageous in case one wishes to target only proliferating tumor cells. Owing to the heterogeneous proliferation rate in different parts of a tumor, however, it could be desirable, under some circumstances, to be able to target even the fraction of nonproliferating tumor cells. This can now be obtained by the use of lentivirus (2) or by switching to the use of adenoviruses that can target both dividing and quiescent cells but also induce unwanted inflammmatory reactions from the host. PMID- 22323261 TI - Use of gene gun for genetic immunotherapy : in vitro and in vivo methods. AB - A major thrust in the application of gene transfer technology for cancer therapy has been the modulation of the immune response. There has been a veritable explosion of information regarding the components of the immune response that are required to generate a meaningful cellular response to tumorassociated antigens (TAAs) capable of eliciting rejection of established tumor. Many of the preclinical and clinical immunogenetic studies have focused on melanoma. Historically, melanoma has been an immunoresponsive tumor for which several melanoma TAAs have been identified. PMID- 22323262 TI - Role of cytokines in pathology of melanoma and use of biologic response modifiers in melanoma. AB - Growth of normal cells is regulated by polypeptides that act via specific cellular receptors. Otherwise known as cytokines, these substances include the growth factors that modulate the proliferation of nonimmune cells. Lymphokines or cytokines, on the other hand, are involved in the regulation of immune cells. Advances in the last 15 yr have shown that alterations in cytokines and their receptors may play a central role in the uncontrolled proliferation of tumor cells in vitro, and such cytokine aberrations are possibly responsible for regulation of tumor growth in vivo. PMID- 22323263 TI - Surgical techniques for treatment of primary cutaneous melanoma. AB - ABSTRUCT: The incidence and mortality rates of melanoma increased dramatically from 1973 to 1994, rising 120.5 and 38.9%, respectively (1). From 1990 to 1994, men had higher incidence (17.3/100,000) and mortality rates (3.5/100,000) than women (incidence: 11.6/100,000; mortality: 1.7/100,000) and had more melanomas on the trunk or the head and neck; women had more on the lower limbs, but the largest increases for an anatomic site were for the trunk. Incidence rates for birth cohorts born after 1945 seem to be stabilizing. Mortality rates of melanoma are declining for women born in the 1930s or later and men born since the 1950s. PMID- 22323264 TI - Utility of fine-needle aspiration biopsy for prospective analysis of patients undergoing therapy for metastatic melanoma. AB - Many of the recent advancements in the area of tumor immunobiology have allowed us to focus our efforts on the experimental treatment of patients with metastatic melanoma. It has been both a frustrating and often a seemingly futile effort on the parts of physicians and researchers alike in treating such patients. The last decade of research has resulted in a paradigm shift in our understanding of the immunologic interactions between a tumor cell and the host immune response. The discovery and clinical application of tumor-associated antigens has allowed for a selective and highly specific approach to the treatment of patients with stage IV metastatic melanoma (1). PMID- 22323265 TI - A molecular technique useful in the detection of occult metastases in patients with melanoma : rt-PCR analysis of sentinel lymph nodes and peripheral blood. AB - When cutaneous melanoma is confined to the skin, simple excision with adequate margins will usually cure the patient (1,2). Local recurrences do occur but reexcision still results in a very high cure rate. When cutaneous melanoma spreads beyond the primary site, the metastases are predominantly by way of the lymphatics. If in-transit disease or regional lymph node involvement is present, the 5-yr survival rate drops to approx 60% (1-3). Accurate staging of the locoregional lymphatic basin is thus extremely important. Pre- operative lymphoscintigraphy followed by selective lymphadenectomy has revolutionized the staging of cutaneous melanoma by delivering to the pathologist only those nodes that are most likely to contain metastatic cells (4). A close examination of these sentinel lymph nodes (SLNs) by serial sectioning and immunohistochemical staining can detect very minute quantities of melanoma. This type of detailed examination is impossible in standard lymphadenectomy specimens that can contain 20-40 lymph nodes. The standard technique used to examine large numbers of lymph nodes is to examine only 1-5% of each node using hematoxylin and eosin staining. This can obviously miss micrometastatic disease and understage the patient. PMID- 22323266 TI - Immunoscope analysis of T-lymphocytes infiltrating melanocytic tumors. AB - Melanomas are most frequently infiltrated by actively proliferating T-lymphocytes (1). Some of these T-cells are cytolytic and recognize peptide antigens derived from melanoma-specific antigens (2). However, with the noteworthy exception of rare immune-mediated, sponaneous regressions of melanomas (3), or in the particular case of the halo nevus phenomenon in which normal melanocytes are killed by CD8(+)-specific T-cells (4), the ongoing melanocyte-specific T-cell responses are most frequently incapable of controlling the growth of the tumor, resulting in the malignant melanocytic tumors escaping an otherwise specific immune T-cell response. The understanding of the mechanisms that underlie the switch of efficient to inefficient (and vice versa) T-cell responses is thus of primary importance in conceiving specific immunotherapies of melanomas. PMID- 22323267 TI - T-cell receptor clonotype mapping using denaturing gradient gel electrophoresis : analysis of clonal T-cell responses in melanoma. AB - Melanoma cells are considered to be immunogenic because they express melanoma associated antigens that are recognized by autologous T-cells. The role of T lymphocytes in the host's immune response to cancer in general and to melanoma in particular has been studied intensively during the past decade, and an immense amount of data have strengthened the notion that a functional and specific antimelanoma T-cell response operates in melanoma patients (1,2). This assumption has been strongly reinforced by the demonstration of clonotypic T-cells in both primary and metastatic melanoma (3,4). Nevertheless, the prognosis of metastatic melanoma is one of the most unfavorable in medicine. The coexistence of tumor specific immunity with a progressing tumor remains a major paradox of tumor immunology and highlights the urgency to reveal new insights into the biology of antitumor T-cells. PMID- 22323268 TI - Methods for Use of Peptide-MHCTetramers in Tumor Immunology. AB - Direct analysis of T-cells of defined specificity and phenotype, without in vitro manipulation that accompanies limiting dilution analysis or other restimulation protocols for evaluating precursor frequency, provides the most accurate representation possible of in vivo events. The natural ligand of the T-cell receptor (TCR), the peptide-major histocompatibility, could be used to identify T cells of a given specificity, but the use of a single peptide-MHC would fail because the affinity of the peptide-MHC for its TCR ligand is characterized by a very fast dissociation rate (1,2). A tetrameric peptide-MHC, however, exhibits sufficient affinity for its TCR ligand to permit its use as a staining reagent in flow cytometry so that peptide-specific T-cells can be visualized by fluorescent markers conjugated to the tetramer (3,4). By combining this approach with fluorescent antibodies staining phenotypic markers or intra- cellular cytokines, this novel and powerful technology now provides a more rapid and informative assessment of antigen-specific T-cells in a given population. Furthermore, sorting individual tetramer+ cells provides an expeditious means for detailed single cell analysis or sorting followed by in vitro expansion. We and others have demonstrated that peptide-MHC tetramers can be used for the purposes discussed in the next sections. PMID- 22323269 TI - Prenatal sonographic diagnosis of congenital varicella syndrome. AB - Congenital varicella syndrome is a rare disorder occurring in less than 1% of maternal varicella during early pregnancy but is associated with high fetal morbidity and mortality. This case report aimed to describe the sonographic features of congenital varicella syndrome following maternal varicella. Well documented maternal chicken pox was made at 12 weeks of gestation and prenatal ultrasound was performed at 16 weeks. Striking sonographic features included hydropic changes and disseminated calcifications in multiple organs, especially liver and myocardium. Elective termination of pregnancy was done at 17 weeks. The presence of disseminated calcifications could suggest the diagnosis of congenital varicella syndrome. PMID- 22323270 TI - New iron-sulfur clusters help hydrogenases tolerate oxygen. AB - One S less: recent crystallographic studies have revealed a new, oxygen-tolerant kind of iron-sulfide cluster [4Fe-3S], which contains only three rather than four sulfur atoms in its cage (see picture; yellow=S, red=Fe, blue=N, green=cysteine). It is proposed that the cluster's ability to transfer multiple electrons increases the oxygen tolerance by enabling the enzyme to reduce O(2) rapidly, converting the dioxygen into harmless water before it can damage the protein. PMID- 22323271 TI - Measuring shear strength of soft-tissue adhesives. AB - A method for evaluating strength of adhesives for hydrogels and soft tissues is presented. Quantitative measurements of shear strength for applications in tissue engineering and biomedicine are performed in torsion using a rheometer. Small, disk shaped specimens of soft biological tissues and/or hydrogels (8 mm diameter, 1-2 mm thick) are mounted onto rheometer tools and then bonded together using the adhesive to be tested. The torsional loading geometry imposes simple shear without deforming the planar adhesive bond, in contrast to the lap-shear test. It retains the advantages of the napkin ring test while reducing artifacts due to cutting and handling soft specimens. The method is demonstrated by measuring the shear strength of two types of biomedical adhesives (cyanoacrylate and polyethylene glycol-based) between model hydrogels (gelatin) and tissues (corneal stroma and skin). PMID- 22323272 TI - Posterior suture avulsion following cervical cerclage. PMID- 22323273 TI - Increased fructose 1,6-bisphosphate aldolase in plastids enhances growth and photosynthesis of tobacco plants. AB - The Calvin cycle is the initial pathway of photosynthetic carbon fixation, and several of its reaction steps are suggested to exert rate-limiting influence on the growth of higher plants. Plastid fructose 1,6-bisphosphate aldolase (aldolase, EC 4.1.2.13) is one of the nonregulated enzymes comprising the Calvin cycle and is predicted to have the potential to control photosynthetic carbon flux through the cycle. In order to investigate the effect of overexpression of aldolase, this study generated transgenic tobacco (Nicotiana tabacum L. cv Xanthi) expressing Arabidopsis plastid aldolase. Resultant transgenic plants with 1.4-1.9-fold higher aldolase activities than those of wild-type plants showed enhanced growth, culminating in increased biomass, particularly under high CO2 concentration (700 ppm) where the increase reached 2.2-fold relative to wild-type plants. This increase was associated with a 1.5-fold elevation of photosynthetic CO2 fixation in the transgenic plants. The increased plastid aldolase resulted in a decrease in 3-phosphoglycerate and an increase in ribulose 1,5-bisphosphate and its immediate precursors in the Calvin cycle, but no significant changes in the activities of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) or other major enzymes of carbon assimilation. Taken together, these results suggest that aldolase overexpression stimulates ribulose 1,5-bisphosphate regeneration and promotes CO2 fixation. It was concluded that increased photosynthetic rate was responsible for enhanced growth and biomass yields of aldolase-overexpressing plants. PMID- 22323275 TI - Ultrafast polymerization inhibition by stimulated emission depletion for three dimensional nanolithography. AB - To identify the depletion mechanism in the stimulated-emission-depletion (STED) inspired photoresist composed of a ketocoumarin photoinitiator in pentaerythritol tetraacrylate, we perform lithography with pulsed excitation and tunable delayed depletion. A fast component can unambiguously be assigned to stimulated emission. Our results allow the systematical optimization of the conditions in next generation STED direct-laser-writing optical lithography. PMID- 22323274 TI - Comparative transcriptomics and proteomics analysis of citrus fruit, to improve understanding of the effect of low temperature on maintaining fruit quality during lengthy post-harvest storage. AB - Fruit quality is a very complex trait that is affected by both genetic and non genetic factors. Generally, low temperature (LT) is used to delay fruit senescence and maintain fruit quality during post-harvest storage but the molecular mechanisms involved are poorly understood. Hirado Buntan Pummelo (HBP; Citrus grandis * C. paradis) fruit were chosen to explore the mechanisms that maintain citrus fruit quality during lengthy LT storage using transcriptome and proteome studies based on digital gene expression (DGE) profiling and two dimensional gel electrophoresis (2-DE), respectively. Results showed that LT up regulated stress-responsive genes, arrested signal transduction, and inhibited primary metabolism, secondary metabolism and the transportation of metabolites. Calcineurin B-like protein (CBL)-CBL-interacting protein kinase complexes might be involved in the signal transduction of LT stress, and fruit quality is likely to be regulated by sugar-mediated auxin and abscisic acid (ABA) signalling. Furthermore, ABA was specific to the regulation of citrus fruit senescence and was not involved in the LT stress response. In addition, the accumulation of limonin, nomilin, methanol, and aldehyde, together with the up-regulated heat shock proteins, COR15, and cold response-related genes, provided a comprehensive proteomics and transcriptomics view on the coordination of fruit LT stress responses. PMID- 22323277 TI - Reaction-based two-photon fluorescent probe for turn-on mercury(II) sensing and imaging in live cells. PMID- 22323278 TI - In vivo and in vitro sonographic diagnosis of an encrusted nephrostomy catheter with color doppler twinkling artifact. AB - Encrustation is one of the most common complications that may develop with the use of a nephrostomy catheter. We used the color Doppler twinkling artifact to detect encrustation and obstruction of a nephrostomy catheter in vivo. This was confirmed by in vitro scanning of the catheter after analyzing the radiogram. Color Doppler twinkling artifact may provide useful information on the management of nephrostomy catheters. PMID- 22323279 TI - Implementing organizational physical activity and healthy eating strategies on paid time: process evaluation of the UCLA WORKING pilot study. AB - Integrating organizationally targeted wellness strategies into the routine conduct of business has shown promise in engaging captive audiences at highest risk of obesity and obesity-related health consequences. This paper presents a process evaluation of the implementation of the University of California, Los Angeles, Working Out Regularly Keeps Individuals Nurtured and Going (WORKING) pilot study. WORKING focuses on integrating physical activity and nutrition practices into workplace routine during non-discretionary paid work time. The purpose of the evaluation was to assess the quality of implementation and to understand factors that facilitated or hindered organizations' full uptake of the intervention. Fifteen worksites were randomly assigned to an intervention condition. Qualitative data were gathered through routine site visits and informant interviews conducted throughout each worksite's intervention period. Worksites were classified into one of four implementation success categories based on their level of adoption and maintenance of core intervention strategies. Six key factors emerged that were related to implementation success: site layout and social climate, wellness infrastructure, number and influence of Program Champions, leadership involvement, site innovation and creativity. This pilot study has informed the conduct of WORKING II; a cluster randomized controlled trial aimed at enrolling 60-70 worksites in Los Angeles County. PMID- 22323280 TI - Basic auditory processing deficits in dyslexia: systematic review of the behavioral and event-related potential/ field evidence. AB - A review of research that uses behavioral, electroencephalographic, and/or magnetoencephalographic methods to investigate auditory processing deficits in individuals with dyslexia is presented. Findings show that measures of frequency, rise time, and duration discrimination as well as amplitude modulation and frequency modulation detection were most often impaired in individuals with dyslexia. Less consistent findings were found for intensity and gap perception. Additional factors that mediate auditory processing deficits in individuals with dyslexia and their implications are discussed. PMID- 22323281 TI - Influence of carboxymethyl chitin on stability and biocompatibility of 3D nanohydroxyapatite/gelatin/carboxymethyl chitin composite for bone tissue engineering. AB - A novel three-dimensional (3D) scaffold has been developed from the unique combination of nanohydroxyapatite/gelatin/carboxymethyl chitin (n-HA/gel/CMC) for bone tissue engineering by using the solvent-casting method combined with vapor phase crosslinking and freeze-drying. The surface morphology and physiochemical properties of the scaffold were investigated by dissolvability test, infrared absorption spectra (IR), X-ray diffraction (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM), mechanical testing, and soaking in simulated body fluid (SBF). An optimized (composition and processing parameters) ratio of n-HA:gel:CMC (1:2:1), exhibited ideal porous structure with regular interconnected pores (75-250 MUm) and higher mechanical strength. Result suggested that the divalent (Ca(++)), carboxyl (COO(-)), amino (NH4(+)), and phosphate (PO4(3-)) groups created favorable ionic interactions which facilitated structural stability and integrity of the composite scaffold. The SBF soaking experiment confirmed the apatite nucleation ability, induced by CMC incorporation. Furthermore, hemocompatibility (hemolysis, platelet adhesion, and protein adsorption) and biocompatibility with MG63 osteoblast cells (MTT assay, cell morphology, and confocal studies from within the 3D scaffold) indicated that the structural and dimensional stability of composite scaffold provided an optimal mechanosensory environment for enhancement of cell adhesion, proliferation, and network formation. The n-HA/gel/CMC composite, therefore, may serve as a promising composite scaffold for guided bone regeneration. PMID- 22323284 TI - The mysterious RAMP proteins and their roles in small RNA-based immunity. AB - A new class of prokaryotic RNA binding proteins called Repeat Associated Mysterious Proteins (RAMPs), has recently been identified. These proteins play key roles in a novel type immunity in which the DNA of the host organism (e.g. a prokaryote) has sequence segments corresponding to the sequences of potential viral invaders. The sequences embedded in the host DNA confer immunity by directing selective destruction of the nucleic acid of the virus using an RNA based strategy. In this viral defense mechanism, RAMP proteins have multiple functional roles including endoribonucleotic cleavage and ribonucleoprotein particle assembly. RAMPs contain the classical RNA recognition motif (RRM), often in tandem, and a conserved glycine-rich segment (G-loop) near the carboxyl terminus. However, unlike RRMs that bind single-stranded RNA using their beta sheet surface, RAMPs make use of both sides of the RRM fold and interact with both single-stranded and structured RNA. The unique spatial arrangement of the two RRM folds, facilitated by a hallmark G-loop, is crucial to formation of a composite surface for recognition of specific RNA. Evidence for RNA-dependent oligomerization is also observed in some RAMP proteins that may serve as an important strategy to increase specificity. PMID- 22323285 TI - Rab8a regulates the exocyst-mediated kiss-and-run discharge of the Dictyostelium contractile vacuole. AB - Water expulsion by the contractile vacuole (CV) in Dictyostelium is carried out by a giant kiss-and-run focal exocytic event during which the two membranes are only transiently connected but do not completely merge. We present a molecular dissection of the GTPase Rab8a and the exocyst complex in tethering of the contractile vacuole to the plasma membrane, fusion, and final detachment. Right before discharge, the contractile vacuole bladder sequentially recruits Drainin, a Rab11a effector, Rab8a, the exocyst complex, and LvsA, a protein of the Chediak Higashi family. Rab8a recruitment precedes the nucleotide-dependent arrival of the exocyst to the bladder by a few seconds. A dominant-negative mutant of Rab8a strongly binds to the exocyst and prevents recruitment to the bladder, suggesting that a Rab8a guanine nucleotide exchange factor activity is associated with the complex. Absence of Drainin leads to overtethering and blocks fusion, whereas expression of constitutively active Rab8a allows fusion but blocks vacuole detachment from the plasma membrane, inducing complete fragmentation of tethered vacuoles. An indistinguishable phenotype is generated in cells lacking LvsA, implicating this protein in postfusion detethering. Of interest, overexpression of a constitutively active Rab8a mutant reverses the lvsA-null CV phenotype. PMID- 22323286 TI - A negative feedback loop at the nuclear periphery regulates GAL gene expression. AB - The genome is nonrandomly organized within the nucleus, but it remains unclear how gene position affects gene expression. Silenced genes have frequently been found associated with the nuclear periphery, and the environment at the periphery is believed to be refractory to transcriptional activation. However, in budding yeast, several highly regulated classes of genes, including the GAL7-10-1 gene cluster, are known to translocate to the nuclear periphery concurrent with their activation. To investigate the role of gene positioning on GAL gene expression, we monitored the effects of mutations that disrupt the interaction between the GAL locus and the periphery or synthetically tethered the locus to the periphery. Localization to the nuclear periphery was found to dampen initial GAL gene induction and was required for rapid repression after gene inactivation, revealing a function for the nuclear periphery in repressing endogenous GAL gene expression. Our results do not support a gene-gating model in which GAL gene interaction with the nuclear pore ensures rapid gene expression, but instead they suggest that a repressive environment at the nuclear periphery establishes a negative feedback loop that enables the GAL locus to respond rapidly to changes in environmental conditions. PMID- 22323287 TI - EHD2 regulates caveolar dynamics via ATP-driven targeting and oligomerization. AB - Eps15 homology domain-containing 2 (EHD2) belongs to the EHD-containing protein family of dynamin-related ATPases involved in membrane remodeling in the endosomal system. EHD2 dimers oligomerize into rings on highly curved membranes, resulting in stimulation of the intrinsic ATPase activity. In this paper, we report that EHD2 is specifically and stably associated with caveolae at the plasma membrane and not involved in clathrin-mediated endocytosis or endosomal recycling, as previously suggested. EHD2 interacts with pacsin2 and cavin1, and ordered membrane assembly of EHD2 is dependent on cavin1 and caveolar integrity. While the EHD of EHD2 is dispensable for targeting, we identified a loop in the nucleotide-binding domain that, together with ATP binding, is required for caveolar localization. EHD2 was not essential for the formation or shaping of caveolae, but high levels of EHD2 caused distortion and loss of endogenous caveolae. Assembly of EHD2 stabilized and constrained caveolae to the plasma membrane to control turnover, and depletion of EHD2, resulting in endocytic and more dynamic and short-lived caveolae. Thus, following the identification of caveolin and cavins, EHD2 constitutes a third structural component of caveolae involved in controlling the stability and turnover of this organelle. PMID- 22323288 TI - PRC1 controls spindle polarization and recruitment of cytokinetic factors during monopolar cytokinesis. AB - The central spindle is a postanaphase array of microtubules that plays an essential role in organizing the signaling machinery for cytokinesis. The model by which the central spindle organizes the cytokinetic apparatus is premised on an antiparallel arrangement of microtubules, yet cells lacking spindle bipolarity are capable of generating a distal domain of ectopic furrowing when forced into mitotic exit. Because protein regulator of cytokinesis (PRC1) and kinesin family member 4A (KIF4A) are believed to play a principal role in organizing the antiparallel midzone array, we sought to clarify their roles in monopolar cytokinesis. Although both factors localized to the distal ends of microtubules during monopolar cytokinesis, depletion of PRC1 and KIF4A displayed different phenotypes. Cells depleted of PRC1 failed to form a polarized microtubule array or ectopic furrows following mitotic exit, and recruitment of Aurora B kinase, male germ cell Rac GTPase-activating protein, and RhoA to the cortex was impaired. In contrast, KIF4A depletion impaired neither polarization nor ectopic furrowing, but it did result in elongated spindles with a diffuse distribution of cytokinetic factors. Thus, even in the absence of spindle bipolarity, PRC1 appears to be essential for polarizing parallel microtubules and concentrating the factors responsible for contractile ring assembly, whereas KIF4A is required for limiting the length of anaphase microtubules. PMID- 22323289 TI - The human mitochondrial ISCA1, ISCA2, and IBA57 proteins are required for [4Fe 4S] protein maturation. AB - Members of the bacterial and mitochondrial iron-sulfur cluster (ISC) assembly machinery include the so-called A-type ISC proteins, which support the assembly of a subset of Fe/S apoproteins. The human genome encodes two A-type proteins, termed ISCA1 and ISCA2, which are related to Saccharomyces cerevisiae Isa1 and Isa2, respectively. An additional protein, Iba57, physically interacts with Isa1 and Isa2 in yeast. To test the cellular role of human ISCA1, ISCA2, and IBA57, HeLa cells were depleted for any of these proteins by RNA interference technology. Depleted cells contained massively swollen and enlarged mitochondria that were virtually devoid of cristae membranes, demonstrating the importance of these proteins for mitochondrial biogenesis. The activities of mitochondrial [4Fe 4S] proteins, including aconitase, respiratory complex I, and lipoic acid synthase, were diminished following depletion of the three proteins. In contrast, the mitochondrial [2Fe-2S] enzyme ferrochelatase and cellular heme content were unaffected. We further provide evidence against a localization and direct Fe/S protein maturation function of ISCA1 and ISCA2 in the cytosol. Taken together, our data suggest that ISCA1, ISCA2, and IBA57 are specifically involved in the maturation of mitochondrial [4Fe-4S] proteins functioning late in the ISC assembly pathway. PMID- 22323290 TI - FCH domain only-2 organizes clathrin-coated structures and interacts with Disabled-2 for low-density lipoprotein receptor endocytosis. AB - Clathrin-mediated endocytosis regulates the internalization of many nutrient and signaling receptors. Clathrin and endocytic accessory proteins are recruited to receptors by specific adaptors. The adaptor Disabled-2 (Dab2) recruits its cargoes, including the low-density lipoprotein receptor (LDLR), and mediates endocytosis, even when the major adaptor protein AP2 is depleted. We hypothesized that the accessory proteins normally recruited by AP2 may be recruited by Dab2 if AP2 is absent. We identified one such accessory protein, the F-BAR protein FCH domain only-2 (FCHO2), as a major Dab2-interacting protein. The MU-homology domain (MUHD) of FCHO2 binds directly to DPF sequences in Dab2 that also bind AP2. Disrupting the Dab2-FCHO2 interaction inhibited Dab2-mediated LDLR endocytosis in AP2-depleted cells. Depleting FCHO2 reduced the number but increased the size of clathrin structures on the adherent surface of HeLa cells and inhibited LDLR and transferrin receptor clustering. However, LDLR was internalized efficiently by FCHO2-deficient cells when additional time was provided for LDLR to enter the enlarged structures before budding, suggesting that later steps of endocytosis are normal under these conditions. These results indicate FCHO2 regulates the size of clathrin structures, and its interaction with Dab2 is needed for LDLR endocytosis under conditions of low AP2. PMID- 22323291 TI - Phosphoinositide lipid phosphatase SHIP1 and PTEN coordinate to regulate cell migration and adhesion. AB - The second messenger phosphatidylinositol(3,4,5)P(3) (PtdIns(3,4,5)P(3)) is formed by stimulation of various receptors, including G protein-coupled receptors and integrins. The lipid phosphatases PTEN and SHIP1 are critical in regulating the level of PtdIns(3,4,5)P(3) during chemotaxis. Observations that loss of PTEN had minor and loss of SHIP1 resulted in a severe chemotaxis defect in neutrophils led to the belief that SHIP1 rather than PTEN acts as a predominant phospholipid phosphatase in establishing a PtdIns(3,4,5)P(3) compass. In this study, we show that SHIP1 regulates PtdIns(3,4,5)P(3) production in response to cell adhesion and plays a limited role when cells are in suspension. SHIP1((-)/(-)) neutrophils lose their polarity upon cell adhesion and are extremely adherent, which impairs chemotaxis. However, chemo-taxis can be restored by reducing adhesion. Loss of SHIP1 elevates Akt activation following cell adhesion due to increased PtdIns(3,4,5)P(3) production. From our observations, we conclude that SHIP1 prevents formation of top-down PtdIns(3,4,5)P(3) polarity to facilitate proper cell attachment and detachment during chemotaxis. PMID- 22323292 TI - Nitric oxide-dependent Src activation and resultant caveolin-1 phosphorylation promote eNOS/caveolin-1 binding and eNOS inhibition. AB - Endothelial nitric oxide synthase (eNOS)-mediated NO production plays a critical role in the regulation of vascular function and pathophysiology. Caveolin-1 (Cav 1) binding to eNOS holds eNOS in an inactive conformation; however, the mechanism of Cav-1-mediated inhibition of activated eNOS is unclear. Here the role of Src dependent Cav-1 phosphorylation in eNOS negative feedback regulation is investigated. Using fluorescence resonance energy transfer (FRET) and coimmunoprecipitation analyses, we observed increased interaction between eNOS and Cav-1 following stimulation of endothelial cells with thrombin, vascular endothelial growth factor, and Ca(2+) ionophore A23187, which is corroborated in isolated perfused mouse lung. The eNOS/Cav-1 interaction is blocked by eNOS inhibitor L-N(G)-nitroarginine methyl ester (hydrochloride) and Src kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo [3, 4-d] pyrimidine. We also observe increased binding of phosphomimicking Y14D-Cav-1 mutant transduced in human embryonic kidney cells overexpressing eNOS and reduced Ca(2+)-induced NO production compared to cells expressing the phosphodefective Y14F-Cav-1 mutant. Finally, Src FRET biosensor, eNOS small interfering RNA, and NO donor studies demonstrate NO-induced Src activation and Cav-1 phosphorylation at Tyr-14, resulting in increased eNOS/Cav-1 interaction and inhibition of eNOS activity. Taken together, these data suggest that activation of eNOS promotes Src-dependent Cav-1-Tyr-14 phosphorylation and eNOS/Cav-1 binding, that is, eNOS feedback inhibition. PMID- 22323293 TI - Intermediate progenitors are increased by lengthening of the cell cycle through calcium signaling and p53 expression in human neural progenitors. AB - During development, neurons can be generated directly from a multipotent progenitor or indirectly through an intermediate progenitor (IP). This last mode of division amplifies the progeny of neurons. The mechanisms governing the generation and behavior of IPs are not well understood. In this work, we demonstrate that the lengthening of the cell cycle enhances the generation of neurons in a human neural progenitor cell system in vitro and also the generation and expansion of IPs. These IPs are insulinoma-associated 1 (Insm1)(+)/BTG family member 2 (Btg2)(-), which suggests an increase in a self-amplifying IP population. Later the cultures express neurogenin 2 (Ngn2) and become neurogenic. The signaling responsible for this cell cycle modulation is investigated. It is found that the release of calcium from the endoplasmic reticulum to the cytosol in response to B cell lymphoma-extra large overexpression or ATP addition lengths the cell cycle and increases the number of IPs and, in turn, the final neuron outcome. Moreover, data suggest that the p53-p21 pathway is responsible for the changes in cell cycle. In agreement with this, increased p53 levels are necessary for a calcium-induced increase in neurons. Our findings contribute to understand how calcium signaling can modulate cell cycle length during neurogenesis. PMID- 22323294 TI - Cdc42p and Fus2p act together late in yeast cell fusion. AB - Cell fusion is the key event of fertilization that gives rise to the diploid zygote and is a nearly universal aspect of eukaryotic biology. In the yeast Saccharomyces cerevisiae, several mutants have been identified that are defective for cell fusion, and yet the molecular mechanism of this process remains obscure. One obstacle has been that genetic screens have mainly focused on mating-specific factors, whereas the process likely involves housekeeping proteins as well. Here we implicate Cdc42p, an essential protein with roles in multiple aspects of morphogenesis, as a core component of the yeast cell fusion pathway. We identify a point mutant in the Rho-insert domain of CDC42, called cdc42-138, which is specifically defective in cell fusion. The cell fusion defect is not a secondary consequence of ineffective signaling or polarization. Genetic and morphological data show that Cdc42p acts at a late stage in cell fusion in concert with a key cell fusion regulator, Fus2p, which contains a Dbl-homology domain. We find that Fus2p binds specifically with activated Cdc42p, and binding is blocked by the cdc42-138 mutation. Thus, in addition to signaling and morphogenetic roles in mating, Cdc42p plays a role late in cell fusion via activation of Fus2p. PMID- 22323295 TI - MAL facilitates the incorporation of exocytic uroplakin-delivering vesicles into the apical membrane of urothelial umbrella cells. AB - The apical surface of mammalian bladder urothelium is covered by large (500-1000 nm) two-dimensional (2D) crystals of hexagonally packed 16-nm uroplakin particles (urothelial plaques), which play a role in permeability barrier function and uropathogenic bacterial binding. How the uroplakin proteins are delivered to the luminal surface is unknown. We show here that myelin-and-lymphocyte protein (MAL), a 17-kDa tetraspan protein suggested to be important for the apical sorting of membrane proteins, is coexpressed with uroplakins in differentiated urothelial cell layers. MAL depletion in Madin-Darby canine kidney cells did not affect, however, the apical sorting of uroplakins, but it decreased the rate by which uroplakins were inserted into the apical surface. Moreover, MAL knockout in vivo led to the accumulation of fusiform vesicles in mouse urothelial superficial umbrella cells, whereas MAL transgenic overexpression in vivo led to enhanced exocytosis and compensatory endocytosis, resulting in the accumulation of the uroplakin-degrading multivesicular bodies. Finally, although MAL and uroplakins cofloat in detergent-resistant raft fractions, they are associated with distinct plaque and hinge membrane subdomains, respectively. These data suggest a model in which 1) MAL does not play a role in the apical sorting of uroplakins; 2) the propensity of uroplakins to polymerize forming 16-nm particles and later large 2D crystals that behave as detergent-resistant (giant) rafts may drive their apical targeting; 3) the exclusion of MAL from the expanding 2D crystals of uroplakins explains the selective association of MAL with the hinge areas in the uroplakin delivering fusiform vesicles, as well as at the apical surface; and 4) the hinge associated MAL may play a role in facilitating the incorporation of the exocytic uroplakin vesicles into the corresponding hinge areas of the urothelial apical surface. PMID- 22323296 TI - The yeast acyltransferase Sct1p regulates fatty acid desaturation by competing with the desaturase Ole1p. AB - The degree of fatty acid unsaturation, that is, the ratio of unsaturated versus saturated fatty acyl chains, determines membrane fluidity. Regulation of expression of the fatty acid desaturase Ole1p was hitherto the only known mechanism governing the degree of fatty acid unsaturation in Saccharomyces cerevisiae. We report a novel mechanism for the regulation of fatty acid desaturation that is based on competition between Ole1p and the glycerol-3 phosphate acyltransferase Sct1p/Gat2p for the common substrate C16:0-CoA. Deletion of SCT1 decreases the content of saturated fatty acids, whereas overexpression of SCT1 dramatically decreases the desaturation of fatty acids and affects phospholipid composition. Whereas overexpression of Ole1p increases desaturation, co-overexpression of Ole1p and Sct1p results in a fatty acid composition intermediate between those obtained upon overexpression of the enzymes separately. On the basis of these results, we propose that Sct1p sequesters C16:0-CoA into lipids, thereby shielding it from desaturation by Ole1p. Ta-king advantage of the growth defect conferred by overexpressing SCT1, we identified the acyltransferase Cst26p/Psi1p as a regulator of Sct1p activity by affecting the phosphorylation state and overexpression level of Sct1p. The level of Sct1p phosphorylation is increased when cells are supplemented with saturated fatty acids, demonstrating the physiological relevance of our findings. PMID- 22323297 TI - Influence of passive lower-body heating on muscle metabolic perturbation and high intensity exercise tolerance in humans. AB - The purpose of this investigation was to determine the influence of heat stress on the dynamics of muscle metabolic perturbation during high-intensity exercise. Seven healthy males completed single-legged knee-extensor exercise until the limit of tolerance on two separate occasions. In a randomized order the subjects underwent 40 min of lower-body immersion in warm water at 42 degrees C prior to exercise (HOT) or received no prior thermal manipulation (CON). Following the intervention, muscle metabolism was measured at rest and throughout exercise using (31)P-MRS. The tolerable duration of high-intensity exercise was reduced by 36% after passive heating (CON: 474 +/- 146 vs. HOT: 303 +/- 76 s; P = 0.005). Intramuscular pH was lower over the first 60 s of exercise (CON: 7.05 +/- 0.02 vs. HOT: 7.00 +/- 0.03; P = 0.019) in HOT compared to CON. The rate of muscle [PCr] degradation during exercise was greater in the HOT condition (CON: -0.17 +/ 0.08 vs. HOT: -0.25 +/- 0.10% s(-1); P = 0.006) and pH also tended to change more rapidly in HOT (P = 0.09). Muscle [PCr] (CON: 26 +/- 14 vs. HOT: 29 +/- 10%), [Pi] (CON: 504 +/- 236 vs. HOT: 486 +/- 186%) and pH (CON: 6.84 +/- 0.13 vs. HOT: 6.80 +/- 0.14; P > 0.05) were not statistically different at the limit of tolerance (P > 0.05 for all comparisons). These results suggest that the reduced time-to-exhaustion during high-intensity knee-extensor exercise following lower-body heating might be related, in part, to accelerated rates of change of intramuscular [PCr] and pH towards 'critical' values that limit muscle function. PMID- 22323298 TI - Serum skeletal troponin I following inspiratory threshold loading in healthy young and middle-aged men. AB - The purpose of this study was to determine if serum levels of skeletal troponin I (sTnI, fast and slow isoforms) could provide a sensitive marker of respiratory muscle damage in healthy humans subjected to inspiratory loads. To accomplish this, we studied healthy, young (27 +/- 2 years, Mean +/- SEM, n = 5) and middle aged (55 +/- 5, n = 5) men to (1) determine the magnitude, pattern, and time course of the presence of sTnI in the serum after a single 60 min bout of inspiratory threshold loading [ITL, ~70% of maximal inspiratory pressure (MIP)], (2) determine the distribution and magnitude of DOMS after loading, and (3) compare fast and slow sTnI levels, and their relationship to other markers/indices of muscle injury including delayed onset muscle soreness (DOMS), serum creatine kinase (CK) levels, and force generating capacity of the respiratory muscles [MIP and maximal expiratory pressure (MEP)]. There was a 24 +/- 4 and 27 +/- 3% increase in fast sTnI 1 hour (p < 0.01) and 3 days (p < 0.01) after ITL. Slow sTnI was elevated by 24 +/- 10% (p < 0.05) 4 days postITL. Other indices of respiratory muscle injury such as CK, MIP and MEP did not show a difference in mean data following ITL; DOMS was slightly but significantly increased following ITL. Our results suggest that sTnI has superior sensitivity compared to other biomarkers/indices of skeletal muscle injury. Future studies examining the impact of respiratory muscle injury with ventilator weaning should consider using sTnI as a sensitive marker of skeletal muscle injury. PMID- 22323299 TI - Skeletal muscle glycogen content and particle size of distinct subcellular localizations in the recovery period after a high-level soccer match. AB - Whole muscle glycogen levels remain low for a prolonged period following a soccer match. The present study was conducted to investigate how this relates to glycogen content and particle size in distinct subcellular localizations. Seven high-level male soccer players had a vastus lateralis muscle biopsy collected immediately after and 24, 48, 72 and 120 h after a competitive soccer match. Transmission electron microscopy was used to estimate the subcellular distribution of glycogen and individual particle size. During the first day of recovery, glycogen content increased by ~60% in all subcellular localizations, but during the subsequent second day of recovery glycogen content located within the myofibrils (Intramyofibrillar glycogen, a minor deposition constituting 10 15% of total glycogen) did not increase further compared with an increase in subsarcolemmal glycogen (-7 vs. +25%, respectively, P = 0.047). Conversely, from the second to the fifth day of recovery, glycogen content increased (53%) within the myofibrils compared to no change in subsarcolemmal or intermyofibrillar glycogen (P < 0.005). Independent of location, increment in particle size preceded increment in number of particles. Intriguingly, average particle size decreased; however, in the period from 3 to 5 days after the match. These findings suggest that glycogen storage in skeletal muscle is influenced by subcellular localization-specific mechanisms, which account for an increase in number of glycogen particles located within the myofibrils in the period from 2 to 5 days after the soccer match. PMID- 22323300 TI - Surgical face masks worn by patients with multidrug-resistant tuberculosis: impact on infectivity of air on a hospital ward. AB - RATIONALE: Drug-resistant tuberculosis transmission in hospitals threatens staff and patient health. Surgical face masks used by patients with tuberculosis (TB) are believed to reduce transmission but have not been rigorously tested. OBJECTIVES: We sought to quantify the efficacy of surgical face masks when worn by patients with multidrug-resistant TB (MDR-TB). METHODS: Over 3 months, 17 patients with pulmonary MDR-TB occupied an MDR-TB ward in South Africa and wore face masks on alternate days. Ward air was exhausted to two identical chambers, each housing 90 pathogen-free guinea pigs that breathed ward air either when patients wore surgical face masks (intervention group) or when patients did not wear masks (control group). Efficacy was based on differences in guinea pig infections in each chamber. MEASUREMENTS AND MAIN RESULTS: Sixty-nine of 90 control guinea pigs (76.6%; 95% confidence interval [CI], 68-85%) became infected, compared with 36 of 90 intervention guinea pigs (40%; 95% CI, 31-51%), representing a 56% (95% CI, 33-70.5%) decreased risk of TB transmission when patients used masks. CONCLUSIONS: Surgical face masks on patients with MDR-TB significantly reduced transmission and offer an adjunct measure for reducing TB transmission from infectious patients. PMID- 22323301 TI - Spurious inferences about long-term outcomes: the case of severe sepsis and geriatric conditions. AB - RATIONALE: Survivors of critical illness suffer significant limitations and disabilities. OBJECTIVES: Ascertain whether severe sepsis is associated with increased risk of so-called geriatric conditions (injurious falls, low body mass index [BMI], incontinence, vision loss, hearing loss, and chronic pain) and whether this association is measured consistently across three different study designs. METHODS: Patients with severe sepsis were identified in the Health and Retirement Study, a nationally representative cohort interviewed every 2 years, 1998 to 2006, and in linked Medicare claims. Three comparators were used to assess an association of severe sepsis with geriatric conditions in survivors: the prevalence in the United States population aged 65 years and older, survivors' own pre-sepsis levels assessed before hospitalization, or survivors' own pre-sepsis trajectory. MEASUREMENTS AND MAIN RESULTS: Six hundred twenty three severe sepsis hospitalizations were followed a median of 0.92 years. When compared with the 65 years and older population, surviving severe sepsis was associated with increased rates of low BMI, injurious falls, incontinence, and vision loss. Results were similar when comparing survivors to their own pre sepsis levels. The association of low BMI and severe sepsis persisted when controlling for patients' pre-sepsis trajectories, but there was no association of severe sepsis with injurious falls, incontinence, vision loss, hearing loss, and chronic pain after such controls. CONCLUSIONS: Geriatric conditions are common after severe sepsis. However, severe sepsis is associated with increased rates of only a subset of geriatric conditions, not all. In studying outcomes after acute illness, failing to measure and control for both preillness levels and trajectories may result in erroneous conclusions. PMID- 22323302 TI - Hypoxia-inducible factor 1 mediates nasal polypogenesis by inducing epithelial-to mesenchymal transition. AB - RATIONALE: Nasal polyposis implies a refractory clinical course in case of chronic rhinosinusitis (CRS). Although hypoxia is believed to be associated with nasal polyposis, little is known about the mechanism underlying polypogenesis. OBJECTIVES: To determine if hypoxia drives nasal polyposis by epithelial-to mesenchymal transition (EMT). METHODS: Immunoblotting, immunofluorescence, flow cytometry, and real-time polymerase chain reaction were performed to evaluate EMT and hypoxic markers in human nasal epithelial cells (hNECs) and in sinonasal tissues from patients with CRS with or without polyps. In addition, the effects of hypoxia-inducible factor (HIF)-1alpha inhibitors on nasal polypogenesis were investigated in a murine model. MEASUREMENTS AND MAIN RESULTS: E-cadherin and alpha-smooth muscle actin (alpha-SMA) were down-regulated and up-regulated, respectively, in patients with polyps as compared with patients without polyps. Under hypoxia, hNECs transformed to a mesenchymal shape, and demonstrated representative changes in EMT markers; that is, mesenchymal markers (alpha-SMA, vimentin, and twist) increased but epithelial markers (E-cadherin and beta catenin) decreased. Mechanistically, E-cadherin level was recovered in hypoxia by silencing HIF-1alpha and decreased in normoxia by expressing HIF-1alpha. Furthermore, hypoxia was found to down-regulate PP2Ac phosphatase and up-regulate pSmad3, which led to alpha-SMA induction. In CRS sinonasal specimens, HIF-1alpha expression was found to correlate with E-cadherin loss and alpha-SMA expression. Finally, HIF-1alpha inhibitors suppressed nasal polypogenesis in a murine model. CONCLUSIONS: hNECs undergo EMT during hypoxia and this process is critically mediated by HIF-1alpha and pSmad3. This study shows that hypoxia-induced EMT is likely to contribute to nasal polyposis in CRS, and suggests that HIF-1alpha be viewed as a therapeutic target for nasal polyposis. PMID- 22323303 TI - Effects of positive airway pressure therapy on neurobehavioral outcomes in children with obstructive sleep apnea. AB - RATIONALE: Positive airway pressure therapy is frequently used to treat obstructive sleep apnea in children. However, it is not known whether positive airway pressure therapy results in improvements in the neurobehavioral abnormalities associated with childhood sleep apnea. OBJECTIVES: We hypothesized that positive airway pressure therapy would be associated with improvements in attention, sleepiness, behavior, and quality of life, and that changes would be associated with therapy adherence. METHODS: Neurobehavioral assessments were performed at baseline and after 3 months of positive airway pressure therapy in a heterogeneous group of 52 children and adolescents. MEASUREMENTS AND MAIN RESULTS: Adherence varied widely (mean use, 170 +/- 145 [SD] minutes per night). Positive airway pressure therapy was associated with significant improvements in attention deficits (P < 0.001); sleepiness on the Epworth Sleepiness Scale (P < 0.001); behavior (P < 0.001); and caregiver- (P = 0.005) and child- (P < 0.001) reported quality of life. There was a significant correlation between the decrease in Epworth Sleepiness Scale at 3 months and adherence (r = 0.411; P = 0.006), but not between other behavioral outcomes and adherence. Behavioral factors also improved in the subset of children with developmental delays. CONCLUSIONS: These results indicate that, despite suboptimal adherence use, there was significant improvement in neurobehavioral function in children after 3 months of positive airway pressure therapy, even in developmentally delayed children. The implications for improved family, social, and school function are substantial. Clinical trial registered with www.clinicaltrials.gov (NCT 00458406). PMID- 22323304 TI - DNA hypomethylation at ALOX12 is associated with persistent wheezing in childhood. AB - RATIONALE: Epigenetic changes may play a role in the occurrence of asthma-related phenotypes. OBJECTIVES: To identify epigenetic marks in terms of DNA methylation of asthma-related phenotypes in childhood, and to assess the effect of prenatal exposures and genetic variation on these epigenetic marks. METHODS: Data came from two cohorts embedded in the Infancia y Medio Ambiente (INMA) PROJECT: Menorca (n = 122) and Sabadell (n = 236). Wheezing phenotypes were defined at age 4-6 years. Cytosine-guanine (CpG) dinucleotide site DNA methylation differences associated with wheezing phenotypes were screened in children of the Menorca study using the Illumina GoldenGate Panel I. Findings were validated and replicated using pyrosequencing. Information on maternal smoking and folate supplement use was obtained through questionnaires. Dichlorodiphenyldichloroethylene was measured in cord blood or maternal serum. Genotypes were extracted from genome-wide data. MEASUREMENT AND MAIN RESULTS: Screening identified lower DNA methylation at a CpG site in the arachidonate 12 lipoxygenase (ALOX12) gene in children having persistent wheezing compared with those never wheezed (P = 0.003). DNA hypomethylation at ALOX12 loci was associated with higher risk of persistent wheezing in the Menorca study (odds ratio per 1% methylation decrease, 1.13; 95% confidence interval, 0.99-1.29; P = 0.077) and in the Sabadell study (odds ratio, 1.16; 95% confidence interval, 1.03 1.37; P = 0.017). Higher levels of prenatal dichlorodiphenyldichloroethylene were associated with DNA hypomethylation of ALOX12 in the Menorca study (P = 0.033), but not in the Sabadell study (P = 0.377). ALOX12 DNA methylation was strongly determined by underlying genetic polymorphisms. CONCLUSIONS: DNA methylation of ALOX12 may be an epigenetic biomarker for the risk of asthma-related phenotypes. PMID- 22323305 TI - Early cystic fibrosis lung disease detected by bronchoalveolar lavage and lung clearance index. AB - RATIONALE: Unrecognized airway infection and inflammation in young children with cystic fibrosis (CF) may lead to irreversible lung disease; therefore early detection and treatment is highly desirable. OBJECTIVES: To determine whether the lung clearance index (LCI) is a sensitive and repeatable noninvasive measure of airway infection and inflammation in newborn-screened children with CF. METHODS: Forty-seven well children with CF (mean age, 1.55 yr) and 25 healthy children (mean age, 1.26 yr) underwent multiple-breath washout testing. LCI within and between-test variability was assessed. Children with CF also had surveillance bronchoalveolar lavage performed. MEASUREMENTS AND MAIN RESULTS: The mean (SD) LCI in healthy children was 6.45 (0.49). The LCI was higher in children with CF (7.21 [0.81]; P < 0.001). The upper limit of normal for the LCI was 7.41. Fifteen (32%) children with CF had an elevated LCI. LCI measurements were repeatable and reproducible. Airway infection was present in 17 (36%) children with CF, including 7 (15%) with Pseudomonas aeruginosa. Polymicrobial growth was associated with worse inflammation. The LCI was higher in children with Pseudomonas (7.92 [1.16]) than in children without Pseudomonas (7.02 [0.56]) (P = 0.038). The LCI correlated with bronchoalveolar lavage IL-8 (R(2) = 0.20, P = 0.004) and neutrophil count (R(2) = 0.21, P = 0.001). An LCI below the upper limit of normality had a high negative predictive value (93%) in excluding Pseudomonas. CONCLUSIONS: The LCI is elevated early in CF, especially in the presence of Pseudomonas and airway inflammation. The LCI is a feasible, repeatable, and sensitive noninvasive marker of lung disease in young children with CF. PMID- 22323306 TI - Modification of n-type organic semiconductor performance of perylene diimides by substitution in different positions: two-dimensional pi-stacking and hydrogen bonding. AB - Perylene diimides (PDIs) and their derivatives are active n-type semiconducting materials widely used in organic electronic devices. A series of PDI derivatives have been investigated by quantum chemistry calculations combined with Marcus Hush electron-transfer theory. The substitution of three different sites of a PDI induces large changes in its electron-transfer mobility. 2,5,8,11-Tetrachloro-PDI with four chlorine atoms in ortho positions shows both large electron- and hole transfer mobilities of 0.116 and 0.650 cm(2) V(-1) s(-1) , respectively, indicative of a potentially highly efficient ambipolar organic semiconducting material. The calculated electron-transfer mobility of 1,6,7,12-tetrachloro-PDI is 0.081 cm(2) V(-1) s(-1) , which is in good agreement with the experimental result. Octachloro-PDIs have the largest electron mobility among these derivatives, although the pi system of the central core is twisted. 2D pi stacking and hydrogen bonds formed at the imide positions are responsible for the large mobility. Simulated anisotropic transport mobility curves of these materials prove the magnitude of the mobility that appears when the measuring transistor channel is along the a-axis of the crystal, which is the direction of hydrogen bond formation. PMID- 22323307 TI - Concerted interaction between pnicogen and halogen bonds in XCl-FH2P-NH3 (X=F, OH, CN, NC, and FCC). AB - We analyze the interplay between pnicogen-bonding and halogen-bonding interactions in the XCl-FH(2)P-NH(3) (X=F, OH, CN, NC, and FCC) complex at the MP2/aug-cc-pVTZ level. Synergetic effects are observed when pnicogen and halogen bonds coexist in the same complex. These effects are studied in terms of geometric and energetic features of the complexes. Natural bond orbital theory and Bader's theory of "atoms in molecules" are used to characterize the interactions and analyze their enhancement with varying electron density at critical points and orbital interactions. The physical nature of the interactions and the mechanism of the synergetic effects are studied using symmetry-adapted perturbation theory. By taking advantage of all the aforementioned computational methods, the present study examines how both interactions mutually influence each other. PMID- 22323312 TI - Photoresponsive block copolymer photonic gels with widely tunable photosensitivity by counter-ions. PMID- 22323313 TI - Genes at work in random bouts: stochastically discontinuous gene activity makes cell cycle duration and cell fate decisions variable, thus providing for stem cells plasticity. AB - Cell interdivision periods (IDP) in homogenous cell populations vary stochastically. Another aspect of probabilistic cell behavior is randomness in cell differentiation. These features are suggested to result from competing stochastic events of assembly/disassembly of the transcription pre-initiation complex (PIC) at gene promoters. The time needed to assemble a proper PIC from different proteins, which must be numerous enough to make their combination gene specific, may be comparable to the IDP. Nascent mRNA visualization at defined genes and inferences from protein level fluctuations in single cells suggest that some genes do operate in this way. The onset of mRNA production by such genes may miss the time windows provided by the cell cycle, resulting in cells differentiating into those in which the respective mRNAs are either present or absent. This creates a way to generate cell phenotype diversity in multicellular organisms. PMID- 22323315 TI - Cytotoxicity of new duplex drugs linking 3'-C-ethynylcytidine and 5-fluor-2' deoxyuridine against human melanoma cells. AB - Melanoma is an increasingly common and potentially fatal malignancy of the skin and some mucous membranes. As no cure exists for metastatic disease, there is an urgent need for novel drugs. 2'-Deoxy-5-fluorouridylyl-(3'-5')-3'-C ethynylcytidine [5-FdU(3'-5')ECyd] and 3'-C-ethynylcytidinylyl-(5' -> 1-O)-2-O octadecyl-sn-glycerylyl-(3-O -> 5')-2'-deoxy-5-fluorouridine [ECyd-lipid-5-FdU] represent cytostatic active duplex drugs, which can be metabolized into various active antimetabolites. We evaluated the cytotoxicity of these heterodinucleoside phosphate analogs, their corresponding monomers ECyd and 5-FdU and combinations thereof on six metastatic melanoma cell lines and six ex vivo patient-derived melanoma cells in comparison to current standard cytostatic agents and the BRAF V600E inhibitor Vemurafenib. In vitro (real-time)-proliferation assays demonstrated that 5-FdU(3'-5')ECyd and ECyd-lipid-5-FdU had a high cytotoxic efficacy causing 75% melanoma cell death at concentrations in the nanomolar and micromolar range. Cytotoxicity was conducted by induction of DNA cleavage indicating apoptotic cells. Chicken embryotoxicity demonstrated that the duplex drugs were less toxic than 5-FdU at 0.01 MUM. In vivo the duplex drug 5-FdU(3' 5')ECyd was efficacious in the murine LOX IMVI melanoma xenograph model on administration of 11.2 mg/kg/injection every fourth day. Both duplex drugs are promising novel cytostatic agents for the treatment of malignant melanoma meriting clinical evaluation. PMID- 22323314 TI - Mechanical characteristics of native tendon slices for tissue engineering scaffold. AB - The purpose of this study was to characterize the mechanical behavior of tendon slices with different thicknesses. Tendon slices of 100, 200, 300, 400, and 500 MUm thickness were mechanically tested. The 300 MUm slices were further tested for strength and modulus after 21,000-cycle fatigue testing under different applied strain levels (0, 1, 3, 5, 8, 10, and 12%). The tendon slice structure, morphology, and viability of bone marrow stromal cells (BMSCs) seeded onto the slices were also examined with histology, scanning electron microscopy, and vital cell labeling, respectively. Tendon slices 300 MUm or more in thickness had similar ultimate tensile strength and Young's modulus to the intact tendon bundle. A strain of 5% or less did not cause any structural damage, nor did it change the mechanical properties of a 300 MUm-thick tendon slice after 21,000 cycle fatigue testing. BMSCs were viable between and on the tendon slices after 2 weeks in tissue culture. This study demonstrated that, if tendon slices are used as a scaffold for tendon tissue engineering, slices 300 MUm or more in thickness would be preferable from a mechanical strength point of view. If mechanical stimulation is performed for seeded-cell preparations, 5% strain or less would be appropriate. PMID- 22323316 TI - Internal architecture of zwitterionic polymer brushes regulates nonfouling properties. AB - In this work, we study how film thickness and chain packing density affect the protein-resistant properties of polymer brushes in complex media. Polymer brushes based on dual-functional poly(carboxybetaine acrylamide) (pCB) were prepared via surface-initiated photoiniferter-mediated polymerization. By adjusting UV radiation time and solvent polarity, pCB films with different thicknesses can be achieved and characterized using an ellipsometer. The packing density of pCB polymer chains is directly related to the swelling ratio of swollen to collapsed film thicknesses. Results showed that the dry film thickness alone, used often in the literature, is not sufficient to correlate with nonfouling properties and the chain packing density must be considered for the design of nonfouling surface coatings. PMID- 22323317 TI - Umbilical cord entanglement in monoamniotic twins. PMID- 22323318 TI - Electrophoretic deposition of a reduced graphene-Au nanoparticle composite film as counter electrode for CdS quantum dot-sensitized solar cells. AB - A reduced graphene (RG)-Au nanoparticle composite film is successfully fabricated by electrophoretic deposition and used as counter electrode for quantum dot sensitized solar cells. The RG-Au composite is prepared by one-step microwave assisted reduction of chloroaurate in alkaline solution with graphite oxide dispersion. Under one sun illumination (AM 1.5 G, 100 mW cm(-2)), the cell with a RG-Au counter electrode shows an energy conversion efficiency of 1.36 %, which is higher than those of cells employing conventional Pt or Au counter electrodes, due to the superior combination of highly catalytic Au nanoparticles and the conductive graphene network structure. PMID- 22323319 TI - Water oxidation by electrodeposited cobalt oxides--role of anions and redox-inert cations in structure and function of the amorphous catalyst. AB - For the production of nonfossil fuels, water oxidation by inexpensive cobalt based catalysts is of high interest. Films for the electrocatalysis of water oxidation were obtained by oxidative self-assembly (electrodeposition) from aqueous solutions containing, apart from Co, either K, Li or Ca with either a phosphate, acetate or chloride anion. X-ray absorption spectroscopy (XAS) at the Co K-edge revealed clusters of edge-sharing CoO(6) octahedra in all films, but the size or structural disorder of the Co-oxido clusters differed. Whereas potassium binding is largely unspecific, CaCo(3) O(4) cubanes, which resemble the CaMn(3) O(4) cubane of the biological catalyst in oxygenic photosynthesis, may form, as suggested by XAS at the Ca K-edge. Cyclic voltammograms in a potassium phosphate buffer at pH 7 revealed that no specific combination of anions and redox-inactive cations is required for catalytic water oxidation. However, the anion type modulates not only the size (or order) of the Co-oxido clusters, but also electrodeposition rates, redox potentials, the capacity for oxidative charging, and catalytic currents. On these grounds, structure-activity relations are discussed. PMID- 22323322 TI - The role of the Arquivos Brasileiros de Cardiologia in the new era of non invasive cardiovascular imaging. PMID- 22323323 TI - Ankle-brachial index and ventricular hypertrophy in arterial hypertension. AB - The ankle-brachial index (ABI) is a marker of peripheral arterial disease. Very few reports have correlated this index with left ventricular hypertrophy (LVH), functional capacity (FC) and Framingham risk score (FRS). The objective of this study was to verify the correlation between ABI, LVH, FC and FRS in men with arterial hypertension (AH). Prospective and cross-sectional study of male patients (n = 40) with a mean age of 57.92 +/- 7.61 years and no cardiovascular complications. This population was submitted to ABI measurements, echocardiography (ECHO), exercise test (ET) and laboratory tests. The ABI (right and left) was considered abnormal when the ratio between the highest mean systolic pressures of the ankles and arms was 0.9 or higher than 1.3 mmHg. LVH was identified by transthoracic ECHO and the FC by the ET. Peripheral blood samples were collected to calculate the FRS. Normal ABI values were observed in 33 patients (82.5%), who were included in Group I; seven patients (17.5%) with abnormal ABI constituted Group II. Left ventricular mass index (LVMI) at the ECO were 111.18 +/- 34.34 g/m(2) (Group I) and 150.29 +/- 34.06 g/m(2) (Group II) (p = 0.009). The prevalence of LVH was 4% (Group I) and 35.3% (Group II) (p = 0.01), demonstrating a significant difference between the groups. As for the FC in ET, there was no difference between the groups. Regarding the FRS, the mean in Group I was below that in Group II: 13.18 +/- 2.11 versus 15.28 +/- 1.79 (p = 0.019). In hypertensive patients, the presence of LVH defined by the LVMI was more frequent in cases with abnormal ABI, identifying a higher cardiovascular risk. PMID- 22323324 TI - On-pump versus off-pump coronary-artery bypass surgery: a meta-analysis. AB - There are controversies about the possible benefits of off pump coronary artery bypass grafting (OPCABG) compared to on-pump coronary artery bypass grafting (ONCABG). For a better perspective on this important issue, we performed a meta analysis of randomized controlled trials, comparing the two techniques. The objective of this study was to verify which technique applied in Coronary Artery Bypass Surgery, OPCABG or ONCABG, provides better results through a meta-analysis of published randomized trials comparing the two techniques. We carried out a computer-based literature search in PubMed, Embase, B-on and Science Direct from March 2009 to January 2010. The studies covered were recovered according to predetermined criteria. A systematic review of randomized clinical trials was performed in order to evaluate the differences between the two revascularization techniques (OPCABG versus ONCABG) regarding mortality and morbidity. Selected studies did not include patients at high risk and long-term longitudinal evaluations. The meta-analysis focused on nine randomized clinical trials, corresponding to a total of 75,086 patients, and compared OPCABG to ONCABG. Regarding mortality, a reduction of 18% in the risk of cardiovascular mortality (OR: 0.82, 95%CI: 0.70 to 0.98, p = 0.03) and 27% in the risk of stroke postoperatively (OR: 0.73, 95%CI: 0.63 to 0.85, p = 0.0001) were observed, both in favor of OPCABG. Concerning the occurrence of complications associated with the procedure, no significant differences were found between the two surgical techniques, particularly with regard to the occurrence of kidney complications (OR: 0.97, 95%CI: 0.84-1.14, p = 0, 74) and sepsis (OR 0.98, 95%CI: 0.64-1.51, p = 0.93, respectively). Off-pump CABG significantly reduces the occurrence of major cardiovascular events (mortality and CVA) compared to on-pump CABG surgery. PMID- 22323325 TI - Impact of chronic renal failure on effectiveness of drug-eluting stents. PMID- 22323326 TI - Case 1/2012: 55-year-old male with multiple coronary artery aneurysms due to Kawasaki disease. PMID- 22323327 TI - Propositional debate on biosimilar enoxaparin in Brazil. AB - Some patents of low-molecular-weight heparins (LMWHs) have expired and others are about to expire. Biosimilar versions of those drugs are available for clinical use in several countries. However, skepticism persists about the possibility of obtaining preparations similar to the original drug, because of the complexity of the process to generate LMWHs. In recent years, our laboratory has analyzed biosimilar samples of enoxaparin available for clinical use in Brazil (30 different batches and 70 finished products). Those preparations were assessed regarding their chemical structure, molecular weight distribution, in vitro anticoagulant activity, and pharmacological effects in animal models of thrombosis and bleeding. Our results have clearly shown that biosimilar preparations of enoxaparin are similar to the original drug. Our results have shown that those biosimilar versions of enoxaparin are a valid therapeutic alternative, which are, however, in need of appropriate regulation to ensure compliance with regulatory requirements. PMID- 22323328 TI - Hemodynamic assessment in heart failure: role of physical examination and noninvasive methods. AB - Among the cardiovascular diseases, heart failure (HF) has a high rate of hospitalization, morbidity and mortality, consuming vast resources of the public health system in Brazil and other countries. The correct determination of the filling pressures of the left ventricle by noninvasive or invasive assessment is critical to the proper treatment of patients with decompensated chronic HF, considering that congestion is the main determinant of symptoms and hospitalization. Physical examination has shown to be inadequate to predict the hemodynamic pattern. Several studies have suggested that agreement on physical findings by different physicians is small and that, ultimately, adaptive physiological alterations in chronic HF mask important aspects of the physical examination. As the clinical assessment fails to predict hemodynamic aspects and because the use of Swan-Ganz catheter is not routinely recommended for this purpose in patients with HF, noninvasive hemodynamic assessment methods, such as BNP, echocardiography and cardiographic bioimpedance, are being increasingly used. The present study intends to carry out, for the clinician, a review of the role of each of these tools when defining the hemodynamic status of patients with decompensated heart failure, aiming at a more rational and individualized treatment. PMID- 22323329 TI - Atrioventricular block pathology in cardiomyopathy by desmin deposition. AB - Generally, restrictive cardiomyopathy due to desmin deposition is characterized by restriction to ventricular diastolic filling and different degrees of atrioventricular block (AVB). In this report, we describe the pathological changes of the cardiac conduction system related to AVB. The sinus node, the compact node, and the penetrating bundle (bundle of His) had no abnormalities, however, there was extensive fibrosis of the terminal portions of the branching bundle and the beginning of the left and right bundles at the top of the ventricular septum. The pathogenesis of this fibrous replacement is probably the same that leads to extensive fibrosis of the working ventricular myocardium, and remains to be elucidated. PMID- 22323330 TI - Recurrent myocardial infarction in a patient with papillary fibroelastoma. AB - This report describes a case of a 62 year-old man admitted for recurrent myocardial infarction and normal coronary arteries, caused by coronary embolism from aortic papillary fibroelastoma. Other conditions causing acute coronary syndrome and normal coronary arteries are discussed. A careful evaluation by transthoracic and transesophageal echocardiography is required in this clinical setting. Surgical excision of the tumor is safe and curative. PMID- 22323331 TI - Hyaluronic acid viscosupplements from avian and non-mammalian sources exhibit biocompatibility profiles with unique, source-specific, antigenic profiles. AB - The objective of this study was to evaluate and compare the biocompatibility profiles of hyaluronic acid (HA) viscosupplements from avian and non-mammalian sources. Inflammatory and immune reactions were assessed in models of both clinically relevant and stringent immunological exposure conditions. Experiments were conducted to evaluate tissue reactions and immunological responses and assess antibody formation with the capacity to bind directly to and cross-react with the different viscosupplements. Mice were exposed to viscosupplements using the air pouch inflammation model and specific immunization using Freund's complete adjuvant (FCA). Murine pouch membrane tissue reactions revealed generally mild to moderate responses, with cellular infiltration and cytokine profiles of pouch tissue characteristic of predominantly fibroblastic responses rather than marked inflammatory reactions. In vitro testing indicated that pouch injections did not elicit detectable T-cell proliferative responses, while antibody assays revealed that mice immunized with viscosupplements in FCA and subsequently boosted were capable of mounting an antibody response with a range of specificities. High reactivity to avian serum albumin was seen in sera from mice injected with HA from an avian source, while low positive reactivity to the bacterial antigen Staphylococcal Lipotechoic Acid was observed in sera from mice injected with HA from bacterial sources. These specificities did not indicate any propensity to cross-react, suggesting that patients with adverse immune responses to HA from an avian source should be unresponsive to subsequent injection with HA from a non-avian source. Overall, the findings demonstrate that viscosupplements exhibit good biocompatibility profiles in the murine air pouch, but when provoked to elicit immunological reactions exhibit unique antigenic spectra. These findings suggest that an immunologically mediated immune reaction directed against avian proteins should not necessarily be a contraindication for the administration of non-avian viscosupplements. PMID- 22323332 TI - beta-Globin polymorphisms in Amerindian populations from the Brazilian Amazon. AB - OBJECTIVES: This investigation was performed to examine genetic variation at the beta-globin locus in a sample of 30 healthy individuals from native populations in South America. The patterns of haplotypic variation were compared with those of previous studies including samples for various worldwide populations in an attempt to make inferences about the occupation of the Americas from a deeper temporal perspective than is typically available with haploid markers. METHODS: A 2.67-kb segment containing the beta-globin gene and its flanking regions was examined for genetic variation in a sample of 60 chromosomes from native populations in South America. The fragment was PCR-amplified and directly sequenced. To determine linkage relationships in compound heterozygotes, we used the amplification refractory mutation system. In addition, we assessed genetic variability and differentiation among populations, and we performed tests of selective neutrality. These analyses were performed for Brazilian Amerindian group and other worldwide populations previously studied. RESULTS: Eleven polymorphic sites were found in the studied fragment, which distinguished eight different haplotypes, three recombinants haplotypes (present as single copies) and five previously described haplotypes, including some of those most highly differentiated. Genetic variation found in the pooled sample is substantial. CONCLUSIONS: Although only five known haplotypes are observed in Amazonia, some of these are highly divergent, resulting in patterns of molecular polymorphism equal to or higher than those from other world regions. PMID- 22323333 TI - Development of new hydrogenations of imines and benign reductive hydroaminations: zinc triflate as a catalyst. AB - The hydrogenation of imines to amines in the presence of catalytic amounts of zinc triflate has been demonstrated for the first time. In addition, an efficient procedure for the reductive hydroamination of alkynes to amines is presented using zinc triflate as a catalyst precursor. In both protocols a variety of different functional groups are tolerated, and the reactions proceed smoothly in high yields. PMID- 22323334 TI - Binary mixtures of ionic liquids: a joint approach to investigate their properties and catalytic ability. AB - The growing interest in the properties and applications of ionic liquids has recently led to research into the possibility of using their binary mixtures. This work reports on the effects of binary mixtures of ionic liquids on the outcome of organic reactions such as the mononuclear rearrangement of heterocycles and the solvatochromic behavior of Nile Red. Binary mixtures formed by ionic liquids differing in the structure of the cation and the anion are taken into account. In particular, ionic liquids such as 1-benzyl-3-butylimidazolium bis(trifluoromethanesulfonyl)imide, 1-(2,3,4,5,6-pentafluorobenzyl)-3 butylimidazolium bis(trifluoromethanesulfonyl)imide, and 1-benzyl-3 butylimidazolium tetrafluoroborate, are studied. To achieve a deep understanding of the properties of ionic-liquid binary mixtures, their three-dimensional organization was analyzed by a combination of resonance light scattering, UV/Vis spectroscopy, and (1)H and (19)F NMR spectroscopy. Data collected herein evidence that the most significant changes in the ionic lattice structure, and consequently the most pronounced effects exerted as solvent media, occur when the studied system involves a blend of different anions. PMID- 22323335 TI - Executive attention and working memory in narcoleptic outpatients. AB - OBJECTIVE: This pioneering study aimed to evaluate executive attention and working memory in Brazilian narcoleptic outpatients. METHODS: Narcoleptic group: 19 treated narcoleptic outpatients (13 F; 6 M) (mean age=37.58; SD = 8.93); control group: 19 subjects (15 F; 4 M) (mean age=34.42; SD=12.31). INSTRUMENTS: Epworth Sleepiness Scale - Brazilian Portuguese Version (ESS-BR), Victoria Stroop Test (VST), Trail Making Test (TMT) and Letter-Number Sequencing (LNS) of WAIS III. RESULTS: Significant difference at Excessive Daytime Sleepiness (EDS) (p<0.001) and at working memory (p=0.009) with worse results for narcoleptic patients. Patients were slower at VST-1 (p=0.002), VST-2 (p=0.045) and at TMT-A (p=0.016), TMT-B (p=0.006) and B-A (p=0.024). CONCLUSION: Narcoleptic patients showed higher degrees of EDS, an impaired executive attention at a temporal level and lower performance in working memory when compared to normal controls. PMID- 22323336 TI - Quality of life in patients with HTLV-I associated myelopathy/tropical spastic paraparesis. AB - OBJECTIVE: To assess the quality of life (QoL) of patients with HTLV-I-associate myelopathy/tropical spastic paraparesis (HAM/TSP) and to correlate it with specific aspects of the disease. METHODS: Fifty-seven HAM/TSP patients completed the SF-36 QoL questionnaire. They were also asked about common complaints related to the disease, and we looked for associations between QoL and these complaints. RESULTS: Patients with HAM/TSP showed a strong negative association to QoL. Pain was the condition which most affected their QoL. The practice of physical activity is associated with better QoL in five out of eight domains of the scale. CONCLUSION: HAM/TSP leads to a poor QoL, mostly influenced by pain. Physical activity may have a positive association to QoL of these patients. PMID- 22323337 TI - KMD: Korean Mutation Database for genes related to diseases. AB - The number of known disease-causing mutations has increased dramatically. However, there have been few organized mutation databases developed that are available to the public or not-for-profit entities. Thus, clinicians and diagnostic laboratories had to spend time searching many publications and databases to determine whether a mutation has been previously reported. To assist in genetic diagnoses, the systematic collection and curation of mutations are necessary. The Korean Mutation Database (KMD; http://kmd.cdc.go.kr) is a country specific database of human gene mutations that was established in September 2009. The KMD is a database consolidating mutations of genes related to diseases in Korea; it now contains more than 1,600 mutations from 245 genes. We collected mutation data from diagnostic laboratories and published journals over recent decades in Korea. KMD has been open to the public for searches and registration of mutation data without charge. Our aim is to provide organized information for clinicians and researchers who are interested in genetic diseases. It will be useful not only for researchers in Korea but also for researchers in countries with similar ethnic backgrounds. Ultimately, KMD will be an essential base to improve researches in genetic diseases, developments of diagnostics, and therapeutic optimization. PMID- 22323338 TI - Functional single-nucleotide polymorphisms in the DEFB1 gene are associated with systemic lupus erythematosus in Southern Brazilians. AB - Systemic lupus erythematosus (SLE) is an autoimmune disease that results in inflammation and tissue damage. The etiology of SLE remains unknown, but recent studies have shown that the innate immune system may have a role in SLE pathogenesis through the secretion of small cationic peptides named defensins. The aim of the study was to determine the possible involvement in SLE of three functional single nucleotide polymorphisms (SNPs) (c.-52G>A, c.-44C>G and c. 20G>A) in the 5'UTR region of DEFB1 gene, by analyzing them in a population of 139 SLE patients and 288 healthy controls. The c.-52G>A SNP showed significant differences in allele and genotype frequency distribution between SLE patients and controls (p = 0.01 and p = 0.02 respectively) indicating protection against SLE (A allele, OR = 0.68, AA genotype OR = 0.51). Significant differences were also observed for c.-44C>G SNP, the C/G genotype being associated with susceptibility to SLE (OR = 1.60, p = 0.04). Moreover, statistically significant differences between patients and controls were found for two DEFB1 haplotypes (GCA and GGG, p = 0.01 and p = 0.02 respectively). When considering DEFB1 SNPs and SLE clinical and laboratory manifestations, significant association was found with neuropsychiatric disorders, immunological alterations and anti-DNA antibodies. In conclusion, our results evidence a possible role for the c.-52G>A and c.-44C>G DEFB1 polymorphisms in SLE pathogenesis, that can be considered as possible risk factors for development of disease and disease-related clinical manifestations. Additional studies are needed, to corroborate these results as well as functional studies to understand the biological role of these SNPs in the pathogenesis of SLE. PMID- 22323339 TI - Matrix metalloproteinase-2 functional promoter polymorphism G1575A is associated with elevated circulatory MMP-2 levels and increased risk of cardiovascular disease in systemic lupus erythematosus patients. AB - Matrix metalloproteinase-2 (MMP-2) is a zinc dependent endonuclease that degrades type IV collagen, the major structural component of basement membranes. MMP-2 functional promoter polymorphism G1575A affects circulating level of MMP-2 and may be considered an important genetic determinant of cardiovascular disease (CVD) in systemic lupus erythematosus (SLE) patients. In this study, association between MMP-2 1575A allele with serum MMP-2, neopterin and lipid-lipoprotein levels and with SLE and developing CVD was investigated. The present case-control study consisted of 109 SLE patients with and without CVD (mean age, 35.6 years) and 101 gender- and age-matched, unrelated, healthy controls (mean age, 37.1 years) from the population in the west of Iran. MMP-2 1575G/A polymorphism was detected by polymerase chain reaction (restriction fragment length polymorphism) PCR-RFLP, serum MMP-2, neopterin and lipid levels were determined by enzyme linked immunosorbent assay (ELISA), high-performance liquid chromatography (HPLC) and enzyme assay, respectively. The presence of MMP-2 G1575A allele was found to be associated with SLE and developed CVD (OR = 1.78, p = 0.029 and OR = 3.43, p = 0.025, respectively). The SLE patients with MMP-2 A (G/A + A/A) allele had higher MMP-2 activity (301 +/- 166 vs. 194 +/- 35.5, p = 0.002), neopterin (29.4 +/- 39.4 vs. 7.3 +/- 4.6, p = 0.005), LDL-C (120 +/- 25.7 vs. 87 +/- 39.3, p = 0.045) and lower HDL-C (39.6 +/- 11 vs. 45.9 +/- 11.8, p = 0.031) levels than the control subjects. There was a significantly positive correlation between MMP-2 level with neopterin, total cholesterol and TG levels and negative correlation with HDL-C level in SLE patients with CVD. MMP-2 G1575A allele may be a risk factor for SLE. The carriers of this allele have high levels of MMP-2, neopterin, total cholesterol and TG and lower levels of HDL, thus, they are more likely to develop heart disease. PMID- 22323340 TI - Anti-ganglioside antibodies in patients with systemic lupus erythematosus and neurological manifestations. AB - INTRODUCTION: Anti-ganglioside antibodies (AGA) have been associated with several peripheral neuropathies, such as Miller-Fisher syndrome, Guillain-Barre syndrome and multifocal motor neuropathy. They have also been studied in patients with systemic lupus erythematosus (SLE), focusing on neuropsychiatric manifestations and peripheral neuropathy, but the results are contradictory. OBJECTIVE: To study the presence of AGA in a large cohort of patients with SLE and neuropsychiatric manifestations. PATIENTS AND METHODS: Serum from 65 consecutive patients with SLE and neuropsychiatric manifestations, collected from 1985 to 2009, was tested for the presence of AGA antibodies (GM1, GM2, GM3, asialo-GM1 GD1a, GD1b, GD3, GT1b, GQ1b) using a standard enzyme-linked immunosorbent assay ELISA test (INCAT 1999) and thin layer chromatography (TLC). RESULTS: Positive results for asialo-GM1 (IgM) were found in 10 patients, 6 were positive for asialo-GM1 (IgM and IgG), and 4 were positive for other AGA such as GM1, GM2, GM3, GD1b, GT1b, GD3, (mainly IgM). CONCLUSIONS: Clinical and statistical studies showed no correlation between AGA and neuropsychiatric manifestations of SLE. Although some patients showed reactivity to AGA, these antibodies are not a useful marker of neuropsychiatric manifestations in SLE patients. PMID- 22323341 TI - Diagnosis and non-surgical periodontal management in congenital afibrinogenemia: report of a rare case. AB - Medical records have an important role in the diagnosis and planning treatment modalities of periodontal diseases. Surgical periodontal procedures can pose severe complications if the underlying systemic condition is not recorded. To substantiate this, we present a rare case of afibrinogenemia that was reported to the Department of Periodontics, Narayana Dental College, Nellore, India. The present case report gives details of fibrinogen disorder and the dental management of such cases. PMID- 22323342 TI - Normal intracranial translucency and posterior fossa at 11-13 weeks' gestation in a fetus with closed spina bifida. PMID- 22323343 TI - Silicon-based ion-sensitive field-effect transistor shows negligible dependence on salt concentration at constant pH. PMID- 22323344 TI - High consumption foods and their influence on energy and protein intake in institutionalized older adults. AB - BACKGROUND: The elderly, and especially those attending nursing homes, are at great risk from certain nutritional deficiencies. OBJECTIVE: The aim of this study was to determine which food groups present the highest rates of consumption among the institutionalized elderly and study the energy density of each food group and the number of calories and amount of protein in the total diet of each resident. DESIGN: This was a multicentre observational study of a sample of the institutionalized population over the age of 65. The sample of patients was drawn from four Spanish nursing homes (Santa Coloma Gramanet, Barcelona, Madrid and Bilbao). Our final sample comprised a total of 62 individuals, of whom 22 were men and 40 women, aged between 68 and 96 years. METHODS: Dietary data were collected using the double weight method for each main meal (breakfast, lunch, afternoon snack and dinner), including food type, the quantity of food served and the amount of plate waste for each of the main meals served during 21 days. STATISTICAL ANALYSES: The characteristics of the study population were compared by Student's t-test and chi2 test. The results are expressed in terms of their median values and the interquartile range. To analyse the overall differences between sites, gender and food groups we used Kruskall-Wallis test combined with the Mann-Whitney U-test with Bonferroni correction for multiple comparisons. RESULTS: The food group that was served most was milk products (376.25 g/day). A large amount of potatoes were also served (109.64 g/day) as were sweets and pastries (62.14 g/day). The daily serving of fruit (138.34 g/day) and vegetables (239.47 g/day) was equivalent to no more than that of a daily ration in each case. Milk was the food group with the highest consumption (311 g/day). Most of the energy was provided by groups with a higher energy density like as fats and sauces, sweets and pastries and bread. The mean protein consumption was 82,6 g/day (Table 5) and no significant differences were recorded in this consumption between men and women. CONCLUSIONS: We conclude that there is a need to improve the residents' energy intake and to redistribute their energy and protein intake among the various food groups. An alternative to increasing food portions so as to improve energy intake might involve enriching certain food types. PMID- 22323345 TI - Bioelectrical impedance with different equations versus deuterium oxide dilution method for the inference of body composition in healthy older persons. AB - BACKGROUND: There is no consensus regarding the accuracy of bioimpedance for the determination of body composition in older persons. OBJECTIVE: This study aimed to compare the assessment of lean body mass of healthy older volunteers obtained by the deuterium dilution method (reference) with those obtained by two frequently used bioelectrical impedance formulas and one formula specifically developed for a Latin-American population. DESIGN: A cross-sectional study. PARTICIPANTS: Twenty one volunteers were studied, 12 women, with mean age 72+/ 6.7 years. SETTING: Urban community, Ribeirao Preto, Brazil. MEASUREMENT: Fat free mass was determined, simultaneously, by the deuterium dilution method and bioelectrical impedance; results were compared. In bioelectrical impedance, body composition was calculated by the formulas of Deuremberg, Lukaski and Bolonchuck and Valencia et al. RESULTS: Lean body mass of the studied volunteers, as determined by bioelectrical impedance was 37.8+/-9.2 kg by the application of the Lukaski e Bolonchuk formula, 37.4+/-9.3 kg (Deuremberg) and 43.2+/-8.9 kg (Valencia et. al.). The results were significantly correlated to those obtained by the deuterium dilution method (41.6+/-9.3 Kg), with r=0.963, 0.932 and 0.971, respectively. Lean body mass obtained by the Valencia formula was the most accurate. CONCLUSION: In this study, lean body mass of older persons obtained by the bioelectrical impedance method showed good correlation with the values obtained by the deuterium dilution method. The formula of Valencia et al., developed for a Latin-American population, showed the best accuracy. PMID- 22323346 TI - Agreement between body mass index, calf circumference, arm circumference, habitual energy intake and the MNA in hospitalized elderly. AB - OBJECTIVES: This study aimed to assess the agreement between body mass index, calf circumference, arm circumference, habitual energy intake and the mini nutritional assessment (MNA) and then assess the accuracy of these parameters in relation to the MNA. METHOD: The nutritional status of 132 hospitalized elderly was assessed with the MNA, body mass index (BMI), calf circumference (CC) and arm circumference (AC). Their habitual energy intake (HEI) was also determined. The chi-square and the Mann-Whitney tests were used. The agreement between the nutritional risk criteria and the MNA was determined by the Kappa coefficient. The ROC curve was used to determine the accuracy of the parameters in relation to the MNA and to determine the cut-off values. The significance level was set at 5% (p<0.05). RESULTS: A little more than half the sample (54.5%) was well nourished, 34.9% were at risk of malnutrition and 10.6% were malnourished. There was good agreement only for BMI<22 (Kappa=0.44), with an accuracy (AUC) of 0.78. No agreement was found for the other parameters, their sensitivities were shown to be low. However, CC and AC were very specific for determining the well nourished patients: the CC specificity was 86.1% and AC specificity was 94.4%. The cut-off values determined by the ROC curve were <=23.2 for BMI, <=26.2 for AC and <=32.2 for CC. CONCLUSION: The best parameters to determine nutritional risk in relation to the MNA were AC, BMI and CC. However, these nutritional assessment parameters should be used to replace the MNA for the assessment of hospitalized elderly patients with their current cut-off points. PMID- 22323347 TI - Course of neuropsychiatric symptoms during a 4-year follow up in the REAL-FR cohort. AB - INTRODUCTION: The multicenter PHRC REAL-FR cohort study was designed to follow community-dwelling patients with a diagnosis of Alzheimer's Disease. The present study describes the evolution of neuropsychiatric symptoms (NPS) over 4 years. METHOD: 686 patients were recruited at baseline from 16 French clinical centers. 151 patients were followed over the 4-year interval with 5 Neuropsychiatric evaluations. Neuropsychiatric symptoms were assessed using the Neuropsychiatric inventory (NPI). NPS symptoms were divided into 4 subgroups according to the European Alzheimer Disease Consortium NPI analysis; psychotic subgroup (hallucinations, delusions), hyperactivity subgroup (agitation, aggression, euphoria, disinhibition, irritability, aberrant motor behavior), apathy subgroup (apathy, eating) and affective subgroup (depression, anxiety). Secondly we studied the evolution of the population divided in 4 groups: Apathy only, Hyperactivity only, both Apathy and Hyperactivity, no Apathy no Hyperactivity. RESULTS: At baseline, 100 patients (66%) presented with one or more clinically significant NPI symptoms. This figure increased to 88% at the end of 4-year follow-up (Linear by linear chi square, p<0, 0012). Five NPI symptoms showed significant increases in prevalence: agitation (17,9 to 29,1%), apathy (43,0 to 62,9%) , disinhibition (2,6 to 14,6%), hallucination (2 to 4,6%) and aberrant motor behavior (13,9 to 29,1%). Prevalence of hyperactivity and apathy subgroups increased significantly during the follow-up while the prevalence of affective and psychotic subgroups did not. The number of patients with both apathy and hyperactivity increased (27% to 44%) during the follow-up period whereas the number of patients without these symptoms decreased (p = .009). CONCLUSION: The present study shows that 2 types of symptoms increased primarily over time: Apathy and Hyperactivity. The coexistence of such opposite symptoms over time according to our result should be taken into consideration by clinicians treating those patients. PMID- 22323348 TI - aChE and BuChE inhibition by rivastigmin have no effect on peripheral insulin resistance in elderly patients with Alzheimer disease. AB - BACKGROUND: Insulin resistance (IR) may play a role in most pathogenic processes that promote the development of Late Onset Alzheimer Disease (LOAD). This study was designed to determine the interaction between inhibition of both butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) with rivastigmine and peripheral insulin resistance (IR) in LOAD. METHODS: Seventy-Nine consecutive elderly patients, 31 late onset AD and 48 non-demented patients were evaluated. IR was calculated with HOMA. All of the patients were evaluated through comprehensive geriatric assessments at baseline and in the 6th and 12th months. RESULTS: End of the study, compared to the baseline values, there was a significant increase in the 6th month in both MMSE and IADL scores (t =2.200, p = 0.036 for MMSE and t =2.724, p= 0.011 for IADL, respectively). Rivastigmine was improved both the scores of MMSE and IADL in elderly patients with LOAD, but there was no significance or correlation between HOMA scores and cognitive status. CONCLUSION: In conclusion, inhibition of both BuChE and AChE with rivastigmine was improved the cognition without affecting on the peripheral IR in the elderly patients with LOAD by HOMA. Due to the complexity of disease pathogenesis, it is too early to make general comments, and further longitudinal and long-term studies on this issue are needed. PMID- 22323349 TI - Frailty and cognitive impairment as predictors of mortality in older Mexican Americans. AB - OBJECTIVE: Examine the association between frailty and cognitive impairment as predictors of mortality over a 10-year period in a selected sample of older Mexican Americans. DESIGN: Longitudinal analyses using data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly (1995-96/2004 05). SETTING: Five southwestern states: Texas, New Mexico, Colorado, Arizona, and California. PARTICIPANTS: Mexican Americans aged 67 and older with complete information on the frailty index and the Mini Mental State Examination (MMSE) (n=1,815). MEASUREMENTS: Cognitive impairment determined by a score in the MMSE < 21. Frailty defined as three or more of the following components: 1) weight-loss, 2) weakness, 3) self-reported exhaustion, 4) slow walking speed, and 5) low physical activity level. Sociodemographic characteristics and chronic medical conditions were used as covariates. Mortality was determined using the National Death Index or by proxy. RESULTS: As MMSE score declines over time, the percent of frail individuals increases in a linear fashion. Frailty and cognitive impairment are independent risk factors for mortality after controlling for all covariates (HR 2.03 95% CI 1.57-2.62; HR 1.26 95% CI 1.05-1.52, respectively). When both cognitive impairment and frailty were added to the model, HR for individuals with cognitive impairment was no longer statistically significant. CONCLUSION: The relation between frailty and cognitive impairment needs careful analysis in this population to establish pathways increasing mortality and decreasing quality of life. Our results suggest frailty is a stronger predictor of mortality for older Mexican Americans than cognitive impairment. PMID- 22323350 TI - Pharmacological interventions for geriatric cachexia: a narrative review of the literature. AB - OBJECTIVE: The objective of this review was to investigate the range of pharmacological interventions that have been studied for treatment of geriatric cachexia, and to evaluate their effect on selected clinical outcomes in this population. METHODS: Databases including Medline and Cochrane Central Register of Controlled Trials were searched up to March 2010 with search terms including "cache*", "intervention", "megestrol acetate" and "cytokine inhibitors". Studies investigating subjects with mean age <60y or disease-related cachexia were excluded. Outcomes assessed were weight or BMI, body composition, appetite and laboratory parameters indicative of cachexia. RESULTS: Fifteen publications met the selection criteria, reporting on ten studies. Seven studies investigated use of megestrol acetate (MA): two randomised controlled trials, one case control study, two pre-test/post-test studies and two retrospective chart reviews. Weight/BMI was common amongst outcomes and these studies showed an improvement in weight compared with baseline. MA studies which investigated body composition, appetite and/or laboratory parameters provided some evidence for improvement in these outcomes. Three randomised controlled trials investigated the use of other interventions: ghrelin, growth hormone and vitamin supplementations. All demonstrated a significant increase in lean body mass. The only other outcome of interest in these three trials was weight in one study with a significant increase demonstrated. CONCLUSION: Little investigation has been conducted in this population and the diagnosis of cachexia is problematic however these trials provide preliminary evidence for beneficial outcomes in older adults likely to have cachexia. Further high quality adequately powered prospective studies are necessary to provide effective treatment for geriatric cachexia. PMID- 22323351 TI - Effect of an 8-weeks aerobic training program in elderly on oxidative stress and HSP72 expression in leukocytes during antioxidant supplementation. AB - OBJECTIVE: To investigate the effect of aerobic training in the context of antioxidant supplementation on systemic oxidative stress and leukocytes heat shock protein (Hsp)72 expression in the elderly. DESIGN: Sixteen septuagenarians (8 males and 8 females, mean age 74.6) were supplemented with Vitamin C and E (respectively 500 and 100mg per day) and randomly assigned either to sedentary (AS) or individualized aerobically trained (AT) group for 8 weeks. METHODS: Plasma Vitamin C and E concentrations and aerobic fitness, as well as resting and post graded exercise (GXT) Hsp72 expression in leukocytes, plasma levels of thiobarbituric acid reactive substances (TBARS) and advanced oxidation protein product (AOPP) were measured pre and post training / supplementation. RESULTS: At the end of the intervention, the two groups showed a significant increase in resting plasma vitamin C and E (approximately 50 and 20% increase respectively) and a significant decrease in both resting and post GXT plasma TBARS and AOPP (approximately 25 and 20% decrease respectively). These changes were of similar magnitude in the two groups. The reduced oxidative stress was concomitant with a 15% decreased expression of Hsp72 in monocytes and granulocytes in both groups. CONCLUSION: This study provides evidence that in elderly, increased concentration of antioxidant vitamins C and E is associated with a reduction in oxidative stress and leukocytes Hsp72. In this context, 8 weeks of aerobic training has no impact on oxidative stress or leukocytes Hsp72 expression in elderly people. PMID- 22323352 TI - Effects of nutritional intervention and physical training on energy intake, resting metabolic rate and body composition in frail elderly. a randomised, controlled pilot study. AB - OBJECTIVES: To analyse the effect of nutritional intervention and physical training on energy intake, resting metabolic rate (RMR) and body composition in the frail elderly. DESIGN: Open, randomised, controlled pilot treatment study. SETTING: Community-based research centre. PARTICIPANTS: Ninety-six community dwelling frail elderly people aged 75 and older, 40% men. INTERVENTION: Four treatment arms: i) individual nutritional advice and group sessions on nutrition for the elderly, ii) physical training 2 x 45 minutes per week for 3 months, iii) combined nutritional and physical intervention and iv) control group. MEASUREMENTS: The outcomes were energy intake (4-day food diary); resting metabolic rate (indirect calorimetry) and body composition (anthropometry) performed at baseline, after 3 months' intervention (completed by 79 individuals), and as a follow-up at 9 months (completed by 64 individuals). RESULTS: The training group showed a significantly increased RMR at 3 months. Otherwise, there were no observed differences within or between the four groups. There was no correlation over time between energy intake, RMR and fat free mass. The participants with a low energy intake who managed to increase their energy intake during the study ('responders') had a statistically significantly lower BMI (21 vs. 24) and a lower fat percentage (23 vs. 30) at baseline than the 'non responders'. The 'non-responders' showed a small but statistically significant decrease in body fat percentage at F1, and in body weight, BMI and FFM at 9 months (F3). CONCLUSION: Individual nutrition counselling and physical exercise had no effect on energy intake, RMR or fat free mass in community-dwelling frail elderly people aged 75 and older. Interventions in frail elderly people should be targeted according to the needs of the individual patients. The issues of randomisation, targeting and responders in are problematised and discussed. PMID- 22323353 TI - Basal growth hormone concentration increased following a weight loss focused dietary intervention in older overweight and obese women. AB - OBJECTIVES: Growth and sex steroid hormones decrease with aging and obesity. The effect of dietary weight loss and exercise training lifestyle interventions was examined on hormones as well as determining their relationships with physical function in older obese and overweight adults. DESIGN: Individuals were randomized into one of four 18 month interventions: Healthy Lifestyle (HL), Exercise, Diet, and Exercise-Diet. SETTING: Clinical research setting with facility based exercise and nutrition education and behavior classrooms. PARTICIPANTS: Older (>=60 yrs) overweight and obese (BMI>=28 kg/m(2)) adults with knee osteoarthritis (n=309) were recruited for the study. INTERVENTION: Weight loss goal for Diet groups was >=5%. Exercise groups trained (mostly walking and resistance training) 3 days/week for 60 min/session. MEASUREMENTS: Body weight, growth hormone (GH), corticosterone, sex-hormone binding globulin (SHBG), testosterone, and dehydroepiandrosterone (DHEA) were measured at baseline, 6, and 18 months. Physical function was determined through performance task (6-min walking distance) and self-reported questionnaires (Western Ontario McMaster University Osteoarthritis Index-WOMAC) at similar time points. RESULTS: Diet, Exercise, and Exercise-Diet groups lost 4.9%, 3.5%, and 6.2% of their weight at 18 months, respectively. There was a significant diet treatment effect on GH levels in women as higher concentrations of this hormone were apparent following dietary weight loss intervention (p=0.01). No other hormones were affected by either diet or exercise treatments in men or women. A significant inverse correlation between baseline 6-minute walking distance and SHBG (r=-0.33) was found in men. CONCLUSION: The increase in basal GH levels from the diet treatment in women suggests that this lifestyle behavior intervention may mitigate the age- and obesity-related decreases in growth hormone levels, to help preserve muscle mass, strength, and physical function in older adults. PMID- 22323354 TI - The impact of self-perceived masticatory function on nutrition and gastrointestinal complaints in the elderly. AB - OBJECTIVES: Impaired masticatory function is generally considered to be a contributing factor in the development of malnutrition (1, 2). Furthermore, the exclusion of essential and high-fibre foods from the subjects' diets, due to chewing problems, may induce gastrointestinal disorders (3-5). OBJECTIVE: The impact of masticatory function on malnutrition and gastrointestinal symptoms was evaluated. DESIGN, SETTING, AND PARTICIPANTS: This prospective cross-sectional study was conducted in four nursing homes in Berlin, Germany. 119 residents (mean 86, +/- 8.0 years, 62-102) took part in the study. MEASUREMENTS: Dental status, denture quality, prosthetic condition as well as masticatory ability and gastrointestinal symptoms were evaluated by clinical examination or interview. Nutritional state was determined according to Mini Nutritional Assessment (MNA). RESULTS: The mean Body Mass Index was 24.4, +/-4.9 kg/m2 (17% < 20 kg/m2). The mean MNA was 22.5, +/-4.3, 51.3% below normal. 54.5% of the dentures were poorly fitting. No significant relationships were found between the MNA and dental parameters except loose fit of dentures. However, there was significantly more food avoidance among the subjects with stated chewing problems, discomfort with dentures or ill-fitting dentures and there were significantly more digestive complaints among this group. CONCLUSIONS: Impairments of masticatory function may lead to food avoidance and to a higher incidence of digestive complaints. PMID- 22323355 TI - Prevalence of sleep problems and pain among the elderly in Sweden. AB - BACKGROUND/OBJECTIVES: Sleep problems and pain are common among the elderly and have been shown to affect quality of life. The objectives were to determine the prevalence of sleep problems and pain among the elderly and to compare the two factors in relation to age and gender. DESIGN: A cross-sectional study based on baseline material collected by the Swedish National Study on Aging and Care in Blekinge (SNAC-Blekinge). SETTING: The data were gathered from questionnaires distributed between the years 2001 and 2003 in the municipality of Karlskrona, Sweden. PARTICIPANTS: The participants comprised 1402 Swedish men and women aged 60-96. RESULTS: Of all the participants 70 percent met the criteria for sleep problems and 62 percent indicated some experience of pain during the preceding 4 weeks. Both sleep problems and pain were more frequent among women than men and sleep problems tended to be more common with increasing age. Among the participants who experienced pain during the preciding 4 weeks 77 percent suffered from sleep problems. CONCLUSIONS: Sleep problems and pain are common among older people. Furthermore it is common to suffer from sleep problems when pain has been experienced during the preciding 4 weeks. PMID- 22323356 TI - Prevalence of sarcopenia in healthy community-dwelling elderly in an urban area of Barcelona (Spain). AB - INTRODUCTION: The purpose of this study was to evaluate the prevalence of sarcopenia in a cohort of healthy community-dwelling elderly in an urban area in Barcelona (Spain) for native benchmarks and compare them with those published in other geographical areas. MATERIAL AND METHODS: We prospectively evaluated a series of 200 healthy elderly in the community with preserved functional capacity and absence of cognitive impairment. We performed a comprehensive geriatric assessment and determined anthropometric data, muscle mass (MM) and the muscle mass index (MMI). Assessment of muscle mass was performed by bioelectrical impedance analysis (BIA). The cut-off point for defining sarcopenia MMI was established as less than 2 SD of the mean of a reference group comprising 220 healthy volunteers (20-42 years) in the same area. Results were compared with studies undertaken in the USA, France and Taiwan. RESULTS: The cut-off points obtained were 8.31 Kg/m(2) for men and 6.68 Kg/m2 for women, being similar to those observed in France and Taiwan but different from the USA. The prevalence of sarcopenia observed was 33% for elderly women and 10% for males. On comparison of the prevalence of sarcopenia in the four populations, we observed some differences, particularly in males. CONCLUSIONS: We have defined reference values for sarcopenia, determined by BIA, in our setting. We also observed a remarkable prevalence of sarcopenia in the healthy elderly community, especially in females, showing some differences from those in other geographical regions. PMID- 22323357 TI - Estimation of lean body weight in older women with hip fracture. AB - OBJECTIVE: Lean body weight (LBW) decreases with age while total body fat increases, resulting in altered drug pharmacokinetics. A semi-mechanistic equation estimating LBW using height, weight and sex has been developed for potential use across a wide range of body compositions. The aim of this study was to determine the ability of the LBW equation to estimate dual energy x-ray absorptiometry-derived fat free mass (FFM(DXA)) in a population of older women with recent hip fracture. METHODS: Baseline, four and 12 month data obtained from 23 women enrolled in the Sarcopenia and Hip Fracture study were pooled to give 58 measurements. LBW was estimated using the equation: LBW (kg) = (9270 x Wt) / (8780 + (244 x BMI)). Body composition was classified as: 'normal' (BMI <25kg/m(2) and not sarcopenic), 'overweight-obese' (BMI >25kg/m(2) and not sarcopenic), 'sarcopenic' (sarcopenic and BMI <25kg/m(2)), or 'sarcopenic-obese' (sarcopenic and BMI >25kg/m(2)). The ability of the LBW equation to predict FFMDXA was determined graphically using Bland-Altman plots and quantitatively using the method of Sheiner and Beal. RESULTS: The mean +/- SD age of female participants women was 83+/-7 years (n=23). Sarcopenia was frequently observed (65.2%). Bland-Altman plots demonstrated an underestimation by the LBW equation compared to FFMDXA. The bias (95% CI) and precision (95% CI) calculated using the method of Sheiner and Beal was 0.5kg (-0.7, 1.66kg) and 4.4kg (-3.7, 12.4kg) respectively for pooled data. CONCLUSION: This equation can be used to easily calculate LBW. When compared to FFMDXA, the LBW equation resulted in a small underestimation on average in this population of women with recent hip fracture. The degree of bias may not be clinically important although further studies of larger heterogeneous cohorts are needed to investigate and potentially improve the accuracy of this predictive equation in larger clinical cohorts. PMID- 22323358 TI - IRX4 at 5p15 suppresses prostate cancer growth through the interaction with vitamin D receptor, conferring prostate cancer susceptibility. AB - Recent genome-wide association studies (GWAS) identified a number of prostate cancer (PC) susceptibility loci, but most of their functional significances are not elucidated. Through our previous GWAS for PC in a Japanese population and subsequent resequencing and fine mapping, we here identified that IRX4 (Iroquois homeobox 4), coding Iroquois homeobox 4, is a causative gene of the PC susceptibility locus (rs12653946) at chromosome 5p15. IRX4 is expressed specifically in the prostate and heart, and quantitative expression analysis revealed a significant association between the genotype of rs12653946 and IRX4 expression in normal prostate tissues. Knockdown of IRX4 in PC cells enhanced their growth and IRX4 overexpression in PC cells suppressed their growth, indicating the functional association of IRX4 with PC and its tumor suppressive effect. Immunoprecipitation confirmed its protein-protein interaction to vitamin D receptor (VDR), and we found a significant interaction between IRX4 and VDR in their reciprocal transcriptional regulation. These findings indicate that the PC susceptibility locus represented by rs12653946 at 5p15 is likely to regulate IRX4 expression in prostate which could suppress PC growth by interacting with the VDR pathway, conferring to PC susceptibility. PMID- 22323359 TI - TMPRSS6, but not TF, TFR2 or BMP2 variants are associated with increased risk of iron-deficiency anemia. AB - A variety of conditions lead to anemia, which affects one-quarter of the world's population. Previous genome-wide association studies revealed a number of genetic polymorphisms significantly associated with plasma iron status. To evaluate the association of genetic variants in genes involved in iron delivery and hepcidin regulation pathways with the risk of iron-deficiency anemia (IDA), the following single nucleotide polymorphisms were genotyped in 2139 unrelated elderly Chinese women: rs3811647 (TF), rs7385804 (TFR2), rs235756 (BMP2), and rs855791(V736A) and rs4820268 (TMPRSS6, encoding matriptase-2). We identified common variants in TMPRSS6 as being genetic risk factors for both iron deficiency (OR(rs855791) = 1.55, P = 4.96 * 10(-8)) and IDA (OR(rs855791) = 1.78, P = 8.43 * 10(-9)). TMPRSS6 polymorphisms were also associated with lower serum iron (SI) and hemoglobin levels, consistent with their associations to increased iron deficiency and anemia risk. Variants rs3811647 in TF and rs7385804 in TFR2 were associated with reduced SI, serum transferrin and transferrin saturation levels; however, these variants were not associated with iron deficiency or anemia risk. Our findings suggest that TF, TFR2 and TMPRSS6 polymorphisms are significantly associated with decreased iron status, but only variants in TMPRSS6 are genetic risk factors for iron deficiency and IDA. PMID- 22323361 TI - A DFT study of the structures of Au(x) clusters on a CeO2(111) surface. AB - Studying the structures of metal clusters on oxide supports is challenging due to their various structural possibilities. In the present work, a simple rule in which the number of Au atoms in different layers of Au(x) clusters is changed successively is used to systematically investigate the structures of Au(x) (x=1 10) clusters on stoichiometric and partially reduced CeO(2)(111) surface by DFT calculations. The calculations indicate that the adsorption energy of a single Au atom on the surface, the surface structure, as well as the Au-Au bond strength and arrangement play the key roles in determining Au(x) structures on CeO(2)(111). The most stable Au(2) and Au(3) clusters on CeO(2)(111) are 2D vertical structures, while the most stable structures of Au(x) clusters (x>3) are generally 3D structures, except for Au(7). The 3D structures of large Au(x) clusters in which the Au number in the bottom layer does not exceed that in the top layer are not stable. The differences between Au(x) on CeO(2)(111) and Mg(100) were also studied. The stabilizing effect of surface oxygen vacancies on Au(x) cluster structures depends on the size of Au(x) cluster and the relative positions of Au(x) cluster and oxygen vacancy. The present work will be helpful in improving the understanding of metal cluster structures on oxide supports. PMID- 22323362 TI - Selection maintains MHC diversity through a natural population bottleneck. AB - A perceived consequence of a population bottleneck is the erosion of genetic diversity and concomitant reduction in individual fitness and evolutionary potential. Although reduced genetic variation associated with demographic perturbation has been amply demonstrated for neutral molecular markers, the effective management of genetic resources in natural populations is hindered by a lack of understanding of how adaptive genetic variation will respond to population fluctuations, given these are affected by selection as well as drift. Here, we demonstrate that selection counters drift to maintain polymorphism at a major histocompatibility complex (MHC) locus through a population bottleneck in an inbred island population of water voles. Before and after the bottleneck, MHC allele frequencies were close to balancing selection equilibrium but became skewed by drift when the population size was critically low. MHC heterozygosity generally conformed to Hardy-Weinberg expectations except in one generation during the population recovery where there was a significant excess of heterozygous genotypes, which simulations ascribed to strong differential MHC dependent survival. Low allelic diversity and highly skewed frequency distributions at microsatellite loci indicated potent genetic drift due to a strong founder affect and/or previous population bottlenecks. This study is a real-time examination of the predictions of fundamental evolutionary theory in low genetic diversity situations. The findings highlight that conservation efforts to maintain the genetic health and evolutionary potential of natural populations should consider the genetic basis for fitness-related traits, and how such adaptive genetic diversity will vary in response to both the demographic fluctuations and the effects of selection. PMID- 22323360 TI - Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies. AB - Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 * 10(-8), and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19-1.40) and P= 7.63 * 10(-10). An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants. PMID- 22323363 TI - Maintenance and repair of the lung endothelium does not involve contributions from marrow-derived endothelial precursor cells. AB - Lung endothelium is believed to be a quiescent tissue with the potential to exhibit rapid and effective repair after injury. Endothelial progenitor cells derived from the bone marrow have been proposed as one source of new endothelial cells that may directly contribute to pulmonary endothelial cell homeostasis and repair. Here we use bone marrow transplantation models, using purified hematopoietic stem cells (HSCs) or unfractionated whole marrow, to assess engraftment of cells in the endothelium of a variety of tissues. We find scant evidence for any contribution of bone marrow-derived cells to the pulmonary endothelium in the steady state or after recovery from hyperoxia-induced endothelial injury. Although a rare population of CD45-/CD31+/VECadherin+ bone marrow-derived cells, originating from HSCs, can be found in lung tissue after transplantation, these cells are not readily found in anatomic locations that define the pulmonary endothelium. Moreover, by tracking transplanted bone marrow cells obtained from donor transgenic mice containing endothelial lineage selective reporters (Tie2-GFP), no contribution of bone marrow-derived cells to the adult lung, liver, pancreas, heart, and kidney endothelium can be detected, even after prolonged follow-up periods of 11 months or after recovery from hyperoxic pulmonary endothelial injury. Our findings argue against any significant engraftment of bone marrow-derived cells in the pulmonary vascular endothelium. PMID- 22323364 TI - Transpulmonary flux of S-nitrosothiols and pulmonary vasodilation during nitric oxide inhalation: role of transport. AB - Inhaled nitric oxide (iNO) is used to treat pulmonary hypertension and is being investigated for prevention of bronchopulmonary dysplasia in neonates. Extrapulmonary effects of iNO are widely recognized, but the underlying chemistry and pharmacology are poorly understood. Growing evidence suggests that, in addition to acting via diffusion, NO can be converted into nitrosants capable of reacting with endogenous L-cysteine (L-Cys) in the alveolar lining fluid, forming S-nitrosothiol (SNO)-L-cysteine (CSNO). CSNO can then enter cells via the type L amino acid transporter (LAT). To determine the influence of LAT and supplemental L-Cys on the functional activity of iNO and transpulmonary movement of SNOs or other related species, we exposed C57Bl6 mice to nebulized L-Cys or D-cysteine (D Cys) and/or LAT competitors. Isolated lungs were then perfused with physiologic buffer while effluent was collected to assay perfusate SNOs. Nebulized L-Cys, but not D-Cys, augmented the iNO-induced increase in circulating SNOs in the effluent without altering iNO-induced pulmonary vasodilation. Addition to the perfusate of either L-leucine (L-Leu) or 2-amino-2-norborane carboxylic acid, two distinct LAT competitors, inhibited appearance in the perfusate of SNOs in L-Cys-exposed lungs; a higher concentration of L-Leu significantly inhibited the iNO-induced pulmonary vasodilation as well as SNO accumulation. We conclude that iNO-induced pulmonary vasodilation and the transpulmonary movement of iNO-derived SNOs are mediated in part by formation of extracellular CSNO, uptake by alveolar epithelial LAT, and/or export by LAT from the pulmonary endothelium into the circulation. Therapies that exploit and optimize LAT-dependent SNO transport might improve the efficacy of and clinical outcomes with NO-based therapy by improving systemic SNO delivery. PMID- 22323366 TI - A plasminogen activator inhibitor-1 inhibitor reduces airway remodeling in a murine model of chronic asthma. AB - We previously reported that plasminogen activator inhibitor (PAI)-1 deficiency prevents collagen deposition in the airways of ovalbumin (OVA)-challenged mice. In this study, we explored the therapeutic utility of blocking PAI-1 in preventing airway remodeling, using a specific PAI-1 inhibitor, tiplaxtinin. C57BL/6J mice were immunized with intraperitoneal injections of OVA on Days 0, 3, and 6. Starting on Day 11, mice were challenged with phosphate-buffered saline or OVA by nebulization three times per week for 4 weeks. Tiplaxtinin was mixed with chow and administered orally from 1 day before the phosphate-buffered saline or OVA challenge. Lung tissues were harvested after challenge and characterized histologically for infiltrating inflammatory cells, mucus-secreting goblet cells, and collagen deposition. Airway hyperresponsiveness was measured using whole-body plethysmography. Tiplaxtinin treatment significantly decreased levels of PAI-1 activity in bronchoalveolar lavage fluids, which indicates successful blockage of PAI-1 activity in the airways. The number of infiltrated inflammatory cells was reduced by tiplaxtinin treatment in the lungs of the OVA-challenged mice. Furthermore, oral administration of tiplaxtinin significantly attenuated the degree of goblet cell hyperplasia and collagen deposition in the airways of the OVA-challenged mice, and methacholine-induced airway hyperresponsiveness was effectively reduced by tiplaxtinin in these animals. This study supports our previous findings that PAI-1 promotes airway remodeling in a murine model of chronic asthma, and suggests that PAI-1 may be a novel target of treatment of airway remodeling in asthma. PMID- 22323365 TI - Role of chemokines in the pathogenesis of acute lung injury. AB - Acute lung injury (ALI) is due to an uncontrolled systemic inflammatory response resulting from direct injury to the lung or indirect injury in the setting of a systemic process. Such insults lead to the systemic inflammatory response syndrome (SIRS), which includes activation of leukocytes-alveolar macrophages and sequestered neutrophils-in the lung. Although systemic inflammatory response syndrome is a physiologic response to an insult, systemic leukocyte activation, if excessive, can lead to end organ injury, such as ALI. Excessive recruitment of leukocytes is critical to the pathogenesis of ALI, and the magnitude and duration of the inflammatory process may ultimately determine the outcome in patients with ALI. Leukocyte recruitment is a well orchestrated process that depends on the function of chemokines and their receptors. Understanding the mechanisms that contribute to leukocyte recruitment in ALI may ultimately lead to the development of effective therapeutic strategies. PMID- 22323367 TI - Force oscillations simulating breathing maneuvers do not prevent force adaptation. AB - Airway inflammation in patients with asthma exposes the airway smooth muscle (ASM) to a variety of spasmogens. These spasmogens increase ASM tone, which can lead to force adaptation. Length oscillations of ASM, which occur in vivo due to breathing maneuvers, can attenuate force adaptation. However, in the presence of tone, the force oscillations required to achieve these length oscillations may be unphysiologic (i.e., magnitude greater than the ones achieved due to the swings in transpulmonary pressure required for breathing). In the present study, we applied force oscillations simulating the tension oscillations experienced by the wall of a fourth-generation airway during tidal breathing with or without deep inspirations (DI) to ASM. The goal was to investigate whether force adaptation occurs in conditions mimicking breathing maneuvers. Tone was induced by carbachol (average, 20 nM), and the force-generating capacity of the ASM was assessed at 5 minute intervals before and after carbachol administration using electrical field stimulations (EFS). The results show that force oscillations applied before the introduction of tone had a small effect on the force produced by EFS (declined to 96.8% [P > 0.05] and 92.3% [P < 0.05] with and without DI, respectively). The tone induced by carbachol transiently decreased after a DI and declined significantly (P < 0.05) due to tidal breathing oscillations (25%). These force oscillations did not prevent force adaptation (gain of force of 11.2 +/- 2.2 versus 13.5 +/- 2.7 and 11.2 +/- 3.0% in static versus dynamic conditions with or without DI, respectively). The lack of effect of simulated breathing maneuvers on force adaptation suggests that this gain in ASM force may occur in vivo and could contribute to the development of airway hyperresponsiveness. PMID- 22323369 TI - A major challenge for a generous welfare system: a heavy socio-economic burden of chronic pain conditions in Sweden--and how to meet this challenge. PMID- 22323370 TI - Electroacupuncture alleviates affective pain in an inflammatory pain rat model. AB - Pain has both sensory-discriminative and emotional-affective dimensions. Previous studies demonstrate that electroacupuncture (EA) alleviates the sensory dimension but do not address the affective. An inflammatory pain rat model, produced by a complete Freund adjuvant (CFA) injection into the hind paw, was combined with a conditioned place avoidance (CPA) test to determine whether EA inhibits spontaneous pain-induced affective response and, if so, to study the possibility that rostral anterior cingulate cortex (rACC) opioids underlie this effect. Male Sprague-Dawley rats (250-275 g, Harlan) were used. The rats showed place aversion (i.e. affective pain) by spending less time in a pain-paired compartment after conditioning than during a preconditioning test. Systemic non-analgesic morphine (0.5 and 1.0 mg/kg, i.p.) inhibited the affective reaction, suggesting that the affective dimension is underpinned by mechanisms different from those of the sensory dimension of pain. Morphine at 0.5 and at 1 mg/kg did not induce reward. Rats given EA treatment before pain-paired conditioning at GB 30 showed no aversion to the pain-paired compartment, indicating that EA inhibited the affective dimension. EA treatment did not produce reward or aversive effect. Intra-rACC administration of D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr amide (CTOP), a selective mu opioid receptor antagonist, but not norbinaltorphimine (nor-BNI), a selective kappa opioid receptor antagonist, blocked EA inhibition of the affective dimension. These data demonstrate that EA activates opioid receptors in the rACC to inhibit pain-induced affective responses and that EA may be an effective therapy for both the sensory-discriminative and the affective dimensions of pain. PMID- 22323371 TI - Enhanced pain and autonomic responses to ambiguous visual stimuli in chronic Complex Regional Pain Syndrome (CRPS) type I. AB - Cortical reorganisation of sensory, motor and autonomic systems can lead to dysfunctional central integrative control. This may contribute to signs and symptoms of Complex Regional Pain Syndrome (CRPS), including pain. It has been hypothesised that central neuroplastic changes may cause afferent sensory feedback conflicts and produce pain. We investigated autonomic responses produced by ambiguous visual stimuli (AVS) in CRPS, and their relationship to pain. Thirty CRPS patients with upper limb involvement and 30 age and sex matched healthy controls had sympathetic autonomic function assessed using laser Doppler flowmetry of the finger pulp at baseline and while viewing a control figure or AVS. Compared to controls, there were diminished vasoconstrictor responses and a significant difference in the ratio of response between affected and unaffected limbs (symmetry ratio) to a deep breath and viewing AVS. While viewing visual stimuli, 33.5% of patients had asymmetric vasomotor responses and all healthy controls had a homologous symmetric pattern of response. Nineteen (61%) CRPS patients had enhanced pain within seconds of viewing the AVS. All the asymmetric vasomotor responses were in this group, and were not predictable from baseline autonomic function. Ten patients had accompanying dystonic reactions in their affected limb: 50% were in the asymmetric sub-group. In conclusion, there is a group of CRPS patients that demonstrate abnormal pain networks interacting with central somatomotor and autonomic integrational pathways. PMID- 22323372 TI - Descending pain modulation and its interaction with peripheral sensitization following sustained isometric muscle contraction in fibromyalgia. AB - OBJECTIVE: Sustained isometric muscle contraction (fatiguing contraction) recruits segmental and/or extrasegmental descending inhibition in healthy subjects but not in fibromyalgia (FM). We hypothesized that fatiguing contraction may shift descending pain modulation from inhibition towards facilitation and that the effect of descending pain modulation be dependent on peripheral muscle pain sensitivity. METHODS: Pressure pain thresholds (PPT) were measured from 13 points bilaterally in the upper trapezius muscle and from the mid-point bilaterally in the tibialis anterior before-, immediately after-, and 20 min after fatiguing contraction of shoulder abduction in 22 FM patients and 22 matched healthy controls. Rate of fatigue, pain intensity, and the duration of fatiguing contraction were recorded. RESULTS: The duration of fatiguing contraction was significantly shorter in FM (132.4 +/- 25.2 s) than healthy control groups (286.2 +/- 24.1 s) (P < 0.05), pain intensity was significantly higher in FM (8.25 +/- 0.8 cm) than in healthy controls (5.1 +/- 0.65 cm) (P < 0.01), whereas both groups reported similar fatigue intensity (P > 0.05). Following the contraction, PPTs were increased significantly and heterogeneously in the upper trapezius over time, but not, in the tibialis anterior muscle in healthy controls. However, PPT were significantly decreased over time in the tibialis anterior (P < 0.05), but not, in the upper trapezius in FM. CONCLUSIONS: Descending pain modulation shifts from descending inhibition towards descending facilitation following muscle nociception in FM. Peripheral mechanical hyperalgesia and descending facilitation counterbalance the effect of descending inhibition in FM. PMID- 22323373 TI - Effect of gonadal steroid hormones on formalin-induced temporomandibular joint inflammation. AB - We have recently demonstrated that gonadal steroid hormones decrease formalin induced temporomandibular joint nociception in rats. Given that the attenuation of inflammation is a potential mechanism underlying this antinociceptive effect, we evaluated the effect of gonadal steroid hormones on formalin-induced temporomandibular joint inflammation. Plasma extravasation, a major sign of acute inflammation, and neutrophil migration, an important event related to tissue injury, were evaluated. Formalin induced significantly lower temporomandibular joint plasma extravasation and neutrophil migration in proestrus females than in males and in diestrus females. Since estradiol serum level is high in proestrus females and low in diestrus females and in males, these findings suggest that the high physiological level of estradiol decreases temporomandibular joint inflammation. Estradiol but not progesterone administration in ovariectomized females significantly decreased formalin-induced plasma extravasation and neutrophil migration, an effect that was blocked by the estrogen receptor antagonist ICI 182780. Plasma extravasation and neutrophil migration were not affected by orchiectomy, but testosterone or estradiol administration in orchidectomized males significantly decreased them. The androgen receptor antagonist flutamide blocked the anti-inflammatory effect of testosterone while ICI 182780 blocked that of estradiol in males. Previous intravenous administration of a nonspecific selectin inhibitor significantly decreased formalin-induced temporomandibular joint nociception and neutrophil migration in males, revealing a potent and positive correlation between temporomandibular joint nociception and inflammation. Taken together, these findings demonstrate a pronounced anti-inflammatory effect of estradiol and testosterone in the temporomandibular joint region and suggest that this effect may mediate, at least in part, the antinociceptive effect of these hormones. PMID- 22323374 TI - Can widespread hypersensitivity in carpal tunnel syndrome be substantiated if neck and arm pain are absent? AB - Recent studies demonstrated that patients with carpal tunnel syndrome (CTS) have signs of thermal and mechanical hyperalgesia in extra-median territories suggesting an involvement of central pain mechanisms. As previous studies included patients with shoulder/arm symptoms or neck pain, a potential influence of these coexisting disorders cannot be excluded. This study therefore evaluated whether widespread sensory changes (hypoesthesia or hyperalgesia) are present in patients with unilateral CTS in the absence of coexisting disorders. Twenty-six patients with unilateral CTS with symptoms localised to their hand and 26 healthy controls participated in the study. A comprehensive quantitative sensory testing (QST) protocol including thermal and mechanical detection and pain thresholds was performed over the hands (median, ulnar and radial innervation area), lateral elbows, neck and tibialis anterior muscle. Patients with CTS demonstrated thermal and mechanical hypoesthesia in the hand but not at distant sites. Thermal or mechanical hyperalgesia was not identified at any location with traditional QST threshold testing. However, patients with CTS rated the pain during thermal pain testing significantly higher than healthy participants. This was especially apparent for heat pain ratings which were elevated not only in the affected hand but also in the neck and tibialis anterior muscle. In conclusion, CTS alone in the absence of coexisting neck and arm pain does not account for sensory changes outside the affected hand as determined by traditional QST threshold testing. Elevated pain ratings may however be an early indication of central pain mechanisms. PMID- 22323375 TI - Evaluation of the comparative analgesic effectiveness of transdermal and oral opioids in cancer patients: a propensity score analysis. AB - BACKGROUND: Transdermal delivery systems containing fentanyl or buprenorphine, despite the relatively lack of comparative studies, have reached an impressive share of the market in several countries. In the context of a wider observational study, we applied the propensity score to test the comparative effectiveness of the two routes of administration (oral vs. transdermal). METHODS: We applied the propensity score in a subgroup of patients (starting the World Health Organization third step therapy during the scheduled follow-up of 28 days) using pre-planned primary (pain intensity change) and secondary endpoints, such as increase in doses, need for switching and safety profile. Univariate and multivariate analyses were carried out. RESULTS: Three-hundred sixty-six eligible cases were analysed. We found a difference among the two groups in terms of variables potentially associated with therapy choice and outcomes. After adjusting for propensity score, results were in favour of transdermal delivery systems for the primary endpoint (odds ratio 1.68; p = 0.04). A similar trend was also present for the other secondary endpoints. Only in the case of nausea and vomiting, patients receiving transdermal delivery systems reported a higher frequency of events. CONCLUSION: The application of the propensity score has helped understand better the actual effectiveness of transdermal delivery systems that are at least equivalent to the oral opioids, and even more effective for pain intensity reduction. PMID- 22323376 TI - The effect of validating and invalidating communication on satisfaction, pain and affect in nurses suffering from low back pain during a semi-structured interview. AB - When physicians interview patients with ambiguous or nonspecific symptoms, they often try to reassure them with the purpose of explaining that no dangerous illness or disease is causing the symptoms. Unfortunately the evidence suggests that patients with benign (back) pain instead feel misunderstood, frustrated and unsatisfied with the consultation. Validation is a communication method that focuses on understanding and empathy as a platform for problem solving and it may be applicable for interviews in medical settings. The aim of this study was to examine the effects of validation on patient satisfaction, pain and affect. To this end 28 nurses with (re)current back pain were recruited and randomly assigned to be interviewed in a validating or invalidating condition. Patient satisfaction, affect, pain, disability, pain catastrophizing, and fear of movement were assessed immediately after the interview. The results show that the participants in the validated group were more satisfied with the interview than participants in the invalidating condition. Moreover, they showed a significant decrease on all measures of negative affect as well as for pain. For example, there was a significant between group difference in frustration where frustration decreased in the validation group, while it increased in the invalidation condition. A validating communication style seems to be beneficial for enhancing patient satisfaction, as well as diminishing negative affect and pain intensity ratings. Our results suggest that validation might be a viable technique to use in clinical examinations of patients suffering pain. PMID- 22323377 TI - The effect of post-surgical neuroplasticity on the stability of systemic pain perception: a psychophysical study. AB - BACKGROUND: Surgery-induced neuroplasticity at spinal and supra-spinal levels is assumed to evoke a clinical acute post-operative pain (cAPOP) experience, which is expressed by allodynia and/or hyperalgesia. It remains unclear whether the systemic pain perception measured outside the incision area remains unchanged and whether it is affected by the presence of cAPOP. AIMS: This study explored whether the systemic perception of experimental pain would be altered towards hypersensitivity following elective gynecological surgery unmasked by opioids. METHODS: A perioperative psychophysical evaluation of heat pain thresholds (HPT) and pain estimations were obtained in a remote bodily area before and after surgery among 35 women. RESULTS: The ratings for both pain dimensions of intensity and unpleasantness remained stable following surgery. However, there was a reduction found in HPT the day after surgery (43.6 +/- 2.2 degrees C to 42.2 +/- 3.1 degrees C, p = 0.002). This reduction was associated with lower HPT measured before surgery (r = .56, p < 0.000) and with higher cAPOP intensity obtained at rest (r = -.44, p = 0.008). CONCLUSIONS: This post-surgical allodynia, as reflected by the systemic enhancement of pain perception, may represent plasticity in the central pain pathways at the supra-spinal level. Pre surgical assessment of a patient's pain perception profile may predict certain pain dimensions of post-surgical pain plasticity. The evaluation of individual pain profiles may contribute to a mechanism-based approach aimed to attenuate the cAPOP. PMID- 22323378 TI - Pain catastrophizing influences the use and the effectiveness of distraction in schoolchildren. AB - Distraction is an intuitive way of coping with pain and is often used in children's pain treatment programs. However, empirical evidence concerning the effectiveness of distraction is equivocal. One potential explanation might be that distraction does not work for everyone in every situation. In the current series of studies, we examined the role of pain catastrophizing as an influencing factor of distraction effectiveness. In the first study, we investigated the use of pain coping strategies (including distraction) in schoolchildren (N = 828, aged 8-18 years) by means of a questionnaire. Results indicated that children with higher levels of pain catastrophizing reported using less distraction strategies in daily life than children with lower levels of pain catastrophizing. In the second study, a subsample (N = 81, aged 9-18 years) performed a painful cold pressor task (CPT) (12 degrees C). Participants were randomly assigned to a distraction group, in which an attention-demanding tone-detection task was performed during the CPT, or a control group, in which no distraction task was performed. Results showed that participants in the distraction group were engaged in the distraction task, and reported to have paid less attention to pain than participants in the control group. However, distraction was ineffective in reducing cold pressor pain, and even intensified the pain experience in high catastrophizing children. Caution may be warranted in using distraction as a 'one size fits all' method, especially in high catastrophizing children. PMID- 22323379 TI - Dysfunctional coping in headache: avoidance and endurance is not associated with chronic forms of headache. AB - INTRODUCTION: About 4% of the population suffer from daily or near daily headache, which in most cases evolved from an episodic type of headache. The impact of psychological factors on this process is unknown. It seems reasonable to assume, that besides somatic and social conditions psychological factors like pain-related coping and cognition play an important role, as has been shown for other pain conditions. METHODS: We performed a cross sectional study on pain coping behaviour in 211 patients with migraine and tension type headache. Pain related cognition and coping was investigated using the Kiel Pain Inventory. Prevalence of depression, medication intake and headache characteristics were analysed in regard to chronicity of headache. RESULTS: Overall pain intensity was high in the patient sample. The level of depression increased with headache frequency. Dysfunctional coping, characterized by fear and avoidance is frequently used by headache patients. As in low back pain, also endurance is highly prevalent. Other features known to be associated with chronic headache, like depression and medication overuse, could be confirmed. DISCUSSION: Dysfunctional coping was seen with high prevalence in the entire patient sample (66%). Against our hypothesis, it was not confined to chronic forms of headache. In respect to our data, we discuss the role of avoidance and endurance coping in headache and its possible role in chronicity. PMID- 22323380 TI - A prospective analysis of pain experience, beliefs and attitudes, and pain management of a cohort of Danish surgical patients. AB - BACKGROUND: Adequacy of pain management is a process indicator of health care quality with consequences for patient outcomes and satisfaction. The reported incidence of moderate to severe postoperative pain worldwide is between 20% and 80%. OBJECTIVES: The purpose was to assess the quality of pain management in a cohort of Danish postoperative patients by examining their pain experience, beliefs about pain and pain treatment, and relationships between pain intensity, its effect on function, and pharmacological pain management. METHODS: The American Pain Society's Patient Outcome Questionnaire was administered to a consecutive cohort of Danish patients who had undergone gastrointestinal, gynaecological, orthopaedic or urological surgery within 24 and 72 h of surgery. RESULTS: Findings indicated uncontrolled pain in 45.5% of patients. These patients reported moderate to severe intensity average pain in the previous 24 h, however, 88.4% of the cohort overall stated they were satisfied or very satisfied with pain treatment. Patients who experienced severe pain only received 50% of available strong opioids, 73.3% of available weak opioids, 100% of available non steroidal antiinflammatory drugs (NSAIDS) and paracetamol. Further, analgesics prescribed to be administered at fixed intervals were administered 99% of the time; in contrast, all Pro Re Nata (PRN) orders irrespective of analgesic categories, were administered only 25% of the time. CONCLUSIONS: A number of patients experienced significant pain postoperatively. Although multi-modal analgesics were available, analgesic administration practices did not consistently reflect management responsive to patient needs. Despite this, patients were largely satisfied with the care received suggesting the need for further research to understand how patients perceive the efficacy of pain management. PMID- 22323381 TI - Socio-economic burden of patients with a diagnosis related to chronic pain- register data of 840,000 Swedish patients. AB - BACKGROUND: Chronic pain constitutes a substantial socio-economic challenge but little is known about its actual cost. AIM: To estimate the direct and indirect costs of patients with a diagnosis related to chronic pain (DRCP), to determine variation in these costs across different diagnosis groups, and to identify what resources constitute the most important components of costs. METHODS: Patient level data from three administrative registries in Vastra Gotalandsregionen in Sweden including inpatient and outpatient care, prescriptions, long-term sick leaves, and early retirement were extracted. Patients with a DRCP between January 2004 and November 2009 were selected. RESULTS: In total, 840,000 patients with a DRCP were identified. The mean total costs per patient and year were estimated at 6400 EUR but were higher for patients with cancer (10,400 EUR). Patients on analgesic drugs had more than twice as high costs as patients without analgesic drugs, on average. Indirect costs (sick-leaves and early retirement) constituted the largest cost component (59%) followed by outpatient (21%) and inpatient care (14%), whereas analgesic drug prescriptions constituted less than 1 percent of the total. CONCLUSIONS: The socio-economic burden of patients with a diagnosis related to chronic pain amounts to 32 billion EUR per year, when findings from Vastra Gotalandsregionen are extrapolated to the whole of Sweden. This compares to a fifth of the total Swedish tax burden in 2007 or about a tenth of Swedish GDP. This study does not provide evidence on what costs are caused by chronic pain per se. However, the higher costs of patients on analgesic drugs might indicate that the consequences of pain are of major importance. PMID- 22323382 TI - Gender role expectations of pain mediate sex differences in cold pain responses in healthy Libyans. AB - Previous studies found a relationship between response to experimentally-induced pain and scores for the gender role expectations of pain (GREP) questionnaire. Findings were similar in individuals from America, Portugal and Israel suggesting that gender role expectations may be universal. The aim of this study was to translate and validate Arabic GREP using Factor Analysis and to investigate if sex differences to cold-pressor pain in healthy Libyan men and women are mediated through stereotypical social constructs of gender role expectations and/or pain related anxiety. One hundred fourteen university students (58 women) underwent two cycles of cold pressor pain test to measure pain threshold, tolerance, intensity, and unpleasantness. Participants also completed the Arabic GREP questionnaire and the Pain Anxiety Symptom Scale-Short form (PASS-20). It was found that Libyan men had higher pain thresholds and tolerances than women (mean difference, 95% CI: threshold = 4.69 (s), -0.72 to 10.1, p = 0.005; tolerance = 13.46 (s), 0.5-26.4, p = 0.018). There were significant differences between sexes in 6 out of 12 GREP items (p < 0.004 after Bonferonni adjustment). The results of mediational analysis showed that GREP factors were the mediators of the effects of sex on pain threshold (z = -2.452, p = 0.014 for Self Sensitivity); (z = 2.563, p = 0.01, for Self Endurance) and on pain tolerance (z = -2.538, p = 0.01 for Self Endurance). In conclusion, sex differences in response to pain were mediated by gender role expectations of pain but not pain-related anxiety. PMID- 22323383 TI - Coping strategies and beliefs about pain in veterans with comorbid chronic pain and significant levels of posttraumatic stress disorder symptoms. AB - OBJECTIVES: The purpose of this study was to assess differences in beliefs about pain and coping strategies employed in veterans with comorbid chronic pain and posttraumatic stress disorder (PTSD), compared to veterans with chronic pain alone. It was hypothesized that veterans with comorbid chronic pain and significant levels of PTSD symptomatology would report higher levels of maladaptive coping strategies and beliefs about pain when compared to veterans with pain alone. METHODS: Data were obtained from 194 veterans who completed self report questionnaires as part of their participation in a Psychology Pain Management Program at a northeastern Department of Veterans Affairs healthcare facility. RESULTS: Analyses indicated that 47.4% of the sample scored above the clinical cutoff for PTSD symptomatology on the PTSD Checklist - Military Version (PCL-M). A Multivariate Analysis of Covariance (MANCOVA) was conducted with age and pain intensity as covariates. In support of the hypothesis, veterans with comorbid chronic pain and significant levels of PTSD symptomatology endorsed significantly higher levels of maladaptive coping strategies and beliefs about pain (greater catastrophizing and emotional impact on pain; less control over pain) when compared to veterans with chronic pain alone. DISCUSSION: The results of this study suggest potential explanations for the previously observed negative effect of PTSD on chronic pain. Moreover, the results suggest specific targets for intervention with patients who have comorbid pain and PTSD. PMID- 22323384 TI - Abnormalities of intraterritorial and extraterritorial sensory processing in carpal tunnel syndrome and their pathophysiological significance: a comment on the paper by Schmid et al. (Eur J Pain, 2011). PMID- 22323386 TI - Influence of caffeine on the survival of leaf-cutting ants Atta sexdens rubropilosa and in vitro growth of their mutualistic fungus. AB - BACKGROUND: Leaf-cutting ants collect plant fresh material for the cultivation of their mutualistic fungus. Atta sexdens rubropilosa Forel (Hymenoptera: Formicidae) cause great economic losses through their foraging activity, mainly in agriculture. The main control method is the application of granulated toxic baits incorporated with an active ingredient (AI). The present goal is to evaluate the effect of caffeine on in vitro growth of the mutualistic fungus and on the survival of the leaf-cutting ants, aiming to verify the potential toxicity of this secondary metabolite over these organisms. RESULTS: Three distinct patterns of fungal growth correlated with caffeine concentration were observed: (1) no effect (0.01% caffeine); (2) intermediate growth reduction (0.05% caffeine); (3) drastic growth reduction (0.10 and 0.50% caffeine). The highest caffeine concentration causes fungus death in the first week. As for insect survival, caffeine does not seem to exert any effect. The treatments with diet containing caffeine showed similar values of M50, irrespective of caffeine concentration. CONCLUSION: As caffeine was shown to reduce growth of the mutualistic fungus of Atta sexdens rubropilosa, but with no conclusive effect on insect survival, a hypothetical explanation for the selection of different Coffea species by this leaf-cutting ant species might be associated with caffeine toxicity to the fungus. PMID- 22323387 TI - Fatigue behavior of dental resin composites: flexural fatigue in vitro versus 6 years in vivo. AB - OBJECTIVES: To evaluate fatigue behavior of direct resin composite restorations (Tetric Ceram vs. Grandio) in vitro and in vivo over an observation period of 6 years. METHODS: For the in vitro part, Young's moduli (YM) were calculated and both initial (FS: flexural strength) and fatigue flexural strength (FFL: flexural fatigue limit) were evaluated in a four-point bending setup (n = 15) in distilled water at 37 degrees C. For the in vivo part, 30 patients received 68 direct resin composite restorations of the same materials (Grandio bonded with Solobond M; Tetric Ceram bonded with Syntac). Patients revealed a minimum of two different class II restorations in different quadrants. Epoxy replicas of restored teeth were analyzed under a scanning electron microscope (SEM) at 30* magnification for fatigue characteristics, and 11 selected restorations per group were assessed for marginal fatigue characteristics at 200*. RESULTS: In vitro, YM was 15.7 GPa (Grandio) and 8.7 GPa (Tetric Ceram; p < 0.05), FS was 115.0 MPa (Grandio) versus 101.5 MPa (Tetric Ceram; p > 0.05), and FFL was 63.0 MPa (Grandio) versus 44.3 MPa (Tetric Ceram; p < 0.05). In vivo, no significant difference in fatigue behavior (cracks, chippings) was evaluated for the different materials under investigation. However, marginal breakdown was more pronounced under the SEM for Tetric Ceram (7.9% vs. 4.8% for Grandio; p < 0.05), but without being clinically relevant. SEM analysis exhibited distinct wear patterns after 6 years with no significant differences among materials as well. SIGNIFICANCES: Despite higher in vitro values for YM, FS, and FFL for Grandio, clinical outcome for both resin composite materials over 6 years of clinical service was similar. Higher FFLs in vitro seem to be related to less marginal composite fractures in vivo but without any influence on clinical outcome until the 6 years recall. PMID- 22323388 TI - Expression of a cGMP compatible Lucilia sericata insect serine proteinase debridement enzyme. AB - Previously, we demonstrated the effectiveness of a research grade recombinant chymotrypsin, derived from the larvae of Lucilia sericata, in "debriding" slough/eschar from venous leg ulcers ex vivo. Furthermore, we were able to formulate this enzyme for successful delivery to in vitro wound healing assays, from a prototype hydrogel wound dressing, and showed that enzyme delivered in this way could degrade wound tissue ex vivo. Recently, to progress biotechnological development of the enzyme as a potential therapeutic product, we explored expression using current good manufacturing practice (cGMP) guidelines, and now report that a recombinant chymotrypsin I zymogen from L. sericata can be expressed in the cGMP acceptable strain of Escherichia coli (BLR-DE3). In addition, the conditions required for purification, refolding and activation of the chymotrypsinogen have been determined. The activated enzyme was stable, and effective in digesting wound slough/eschar tissue. To summarise, we have successfully initiated the production and characterisation of a novel cGMP compatible product for use in future clinical trials. PMID- 22323389 TI - A perspective on the role of quantitative structure-activity and structure property relationships in herbicide discovery. AB - BACKGROUND: For the last 15 years the agrochemical industry has focused on using genetic modification to put genes that confer resistance to existing commercial herbicides into crop plants rather than on discovering new herbicides with novel modes of action. The widespread appearance of weeds resistant to those herbicides is now causing the industry to revive their herbicide discovery programs. RESULTS: Elucidation of quantitative structure-activity relationships (QSARs) played a major role in the discovery and development of existing commercial herbicides, but the advent of genetically modified crops has caused published work (at least) in the area to drift from the industrial arena into academic studies. The focus has also turned inward, to refining models for established herbicide targets instead of elucidating new ones. CONCLUSION: This perspective highlights the importance of QSARs and quantitative structure-property relationships (QSPRs) to herbicide discovery in an historical context and provides some guidance as to how they might profitably be applied going forward. PMID- 22323390 TI - Evaluation of a bio-based hydrophobic cellulose laurate film as biomaterial- study on biodegradation and cytocompatibility. AB - The study aims to validate an original bio-based material, obtained by grafting fatty chains, and more especially lauric chains (C12) onto cellulose, for medical applications. The mechanical properties of the synthesized cellulose laurate (C12) are close to those of petrochemical ones such as low density polyethylene. This cellulose-based polymer is transparent, flexible, and hydrophobic. To evaluate the stability of the cellulosic films in biological fluids the samples are soaked in simulated body fluid or blood plasma for a few hours to 6 months, and then submitted to mechanical and chemical analyses. The simultaneously performed cytocompatibility tests were the colony-forming viability, the vitality and cell proliferation tests using NIH 3T3 fibroblasts and MC 3T3 osteoblast-like cells. The results show the stability, the biocompatibility, and the noncytotoxicity of the synthesized cellulose laurate films. This biomaterial may so be considered for surgical applications. PMID- 22323391 TI - Real-time monitoring of shake flask fermentation and off gas using triple disposable noninvasive optical sensors. AB - Bioprocess development is a data-driven process requiring a large number of experiments to be conducted under varying conditions. Small-scale upstream bioprocess development is often performed in shake flasks because they are inexpensive and can be operated in parallel. However, shake flasks are often not equipped to accurately monitor critical process parameters such as pH, dissolved oxygen, and CO2 concentrations. Therefore, there is no definitive information on oxygen supply of growing cells, CO2 formation, and pH changes. Here we describe several shake flask fermentations where all three parameters are monitored by disposable noninvasive optical sensors. The sensitive element of these sensors is a thin, luminescent patch affixed inside the flask. Small electronic devices for excitation and fluorescence detection are positioned outside the shake flask for noninvasive monitoring. By measuring the process parameters throughout the course of the E. coli fermentations, we obtain information that is not routinely available in shake flask fermentations. For example, for cultures with only a few millimeters liquid depth, oxygen limitation can occur at relatively low agitation speeds. Under certain conditions oscillations in dissolved oxygen can occur. An increase in shaker speed and a decrease in culture volume can increase the oxygen availability and reduce the duration of oxygen limitation. PMID- 22323392 TI - The impact of PACS on clinician work practices in the intensive care unit: a systematic review of the literature. AB - OBJECTIVE: To assess evidence of the impact of Picture Archiving and Communication Systems (PACS) on clinicians' work practices in the intensive care unit (ICU). METHODS: We searched Medline, Pre-Medline, CINAHL, Embase, and the SPIE Digital Library databases for English-language publications between 1980 and September 2010 using Medical Subject Headings terms and keywords. RESULTS: Eleven studies from the USA and UK were included. All studies measured aspects of time associated with the introduction of PACS, namely the availability of images, the time a physician took to review an image, and changes in viewing patterns. Seven studies examined the impact on clinical decision-making, with the majority measuring the time to image-based clinical action. The effect of PACS on communication modes was reported in five studies. DISCUSSION: PACS can impact on clinician work practices in three main areas. Most of the evidence suggests an improvement in the efficiency of work practices. Quick image availability can impact on work associated with clinical decision-making, although the results were inconsistent. PACS can change communication practices, particularly between the ICU and radiology; however, the evidence base is insufficient to draw firm conclusions in this area. CONCLUSION: The potential for PACS to impact positively on clinician work practices in the ICU and improve patient care is great. However, the evidence base is limited and does not reflect aspects of contemporary PACS technology. Performance measures developed in previous studies remain relevant, with much left to investigate to understand how PACS can support new and improved ways of delivering care in the intensive care setting. PMID- 22323393 TI - Informatics and data quality at collaborative multicenter Breast and Colon Cancer Family Registries. AB - Quality control and harmonization of data is a vital and challenging undertaking for any successful data coordination center and a responsibility shared between the multiple sites that produce, integrate, and utilize the data. Here we describe a coordinated effort between scientists and data managers in the Cancer Family Registries to implement a data governance infrastructure consisting of both organizational and technical solutions. The technical solution uses a rule based validation system that facilitates error detection and correction for data centers submitting data to a central informatics database. Validation rules comprise both standard checks on allowable values and a crosscheck of related database elements for logical and scientific consistency. Evaluation over a 2 year timeframe showed a significant decrease in the number of errors in the database and a concurrent increase in data consistency and accuracy. PMID- 22323394 TI - New regulation of the right to a dignified dying in Spain: repercussions for nursing. AB - Preserving dignity during the dying process requires reviewing the roles of those involved in the treatment, care methods and decision-making. This article examines the participation and responsibility assigned to nurses regarding decision-making in the final stages of life, as laid out in the Rights to and Guarantee of Dignity for the Individual During the Process of Death Act. This text has been analysed on the levels of socio-cultural practice and discourse practice, using the critical discourse analysis methodology. The results show that, although the law is another result of the social trend of patient empowerment, the responsibility of the nurses is not recognised, and they are left out of the decision-making process in the final stages of life. PMID- 22323395 TI - High-fidelity simulation and legal/ethical concepts: a transformational learning experience. AB - Students in an undergraduate legal and ethical issues course continually told the authors that they did not have time to study for the course because they were busy studying for their clinical courses. Faculty became concerned that students were failing to realize the value of legal and ethical concepts as applicable to clinical practice. This led the authors to implement a transformational learning experience in which students applied legal and ethical course content in a high fidelity human simulation (HFHS) scenario. A preliminary evaluation compared the new HFHS experience with in-person and online student groups using the same case. Based on both student and faculty perceptions, the HFHS was identified as the best of the three approaches for providing a transformational learning experience regarding legal and ethical content. PMID- 22323396 TI - Nurses serving on clinical ethics committees: a qualitative exploration of a competency profile. AB - The competency profile underlying higher nursing education in the Netherlands states that bachelor-prepared nurses are expected to be able to participate in ethics committees. What knowledge, skills and attitudes are involved in this participation is unclear. In five consecutive years, groups of two to three fourth-year (bachelor) nursing students conducted 8 to 11 semi-structured interviews each with nurses in ethics committees. The question was what competencies these nurses themselves say they need to participate in such committees. This article reports the aggregate of the 52 interviews in these five studies. Regarding knowledge, the article reports on health law, ethics and professional knowledge. Regarding skills, communication is mentioned, as are professional skills and skills for 'doing ethics'. An open and respectful attitude towards patients and fellow committee members is required, as well as commitment to patient care, committee work and professional ethics. The right attitude for a nurse in an ethics committee is said to include a reflective and perceptive attitude, along with an awareness of one's own limitations and convictions. A detailed competency profile for nurses' participation in ethics committees as outlined in the recommendations may serve nursing education, institutional committees and nurses themselves to meet the demands of nurses' preparation for clinical ethics consultations. PMID- 22323397 TI - Tracheotomy and children with spinal muscular atrophy type 1: ethical considerations in the French context. AB - Spinal muscular atrophy (SMA) type 1 is a genetic neuromuscular disease in children that leads to degeneration of spinal cord motor neurons. This sometimes results in severe muscular paralysis requiring mechanical ventilation to sustain the child's life. The onset of SMA type 1, the most severe form of the disease, is during the first year of life. These children become severely paralysed, but retain their intellectual capacity. Ethical concerns arise when mechanical ventilation becomes necessary for survival. When professionals assess the resulting life for the child and family, they sometimes fear it will result in unreasonably excessive care. The aim of this article is to present an analysis of ethical arguments that could support or oppose the provision of invasive ventilation in this population. This examination is particularly relevant as France is one of the few countries performing tracheotomies and mechanical ventilation for this condition. PMID- 22323398 TI - Nurses' perceptions of patient participation in hemodialysis treatment. AB - The aim of this study is to explore how nurses perceive patient participations of patients over 75 years old undergoing hemodialysis treatment in dialysis units, and of their next of kin. Ten nurses told stories about what happened in the dialysis units. These stories were analyzed with critical discourse analysis. Three discursive practices are found: (1) the nurses' power and control; (2) sharing power with the patient; and (3) transferring power to the next of kin. The first and the predominant discursive practice can be explained with an ideology of paternalism, in which the nurses used biomedical explanations and the ethical principle of benefice to justify their actions. The second can be explained with an ideology of participation, in which the nurses used ethical narratives as a way to let the patients participate in the treatment. The third seemed to involve autonomous decision-making and the ethical principle of autonomy for the next of kin in the difficult end-of-life decisions. PMID- 22323399 TI - Strigolactones--intriguing biologically active compounds: perspectives for deciphering their biological role and for proposing practical application. AB - Strigolactones are a class of bioactive natural metabolites produced by plant roots and released into the rhizosphere. They were discovered as signals indispensable for the induction of germination of seeds of root parasitic weeds, but since then, interestingly, many other biological, physiological and ecological roles have been described. This has suddenly provoked huge scientific interest in these compounds within different research fields. In this short perspective the attention is focused mainly on the ongoing and future research aimed at deciphering the biological roles of strigolactones that could positively affect, more or less directly, the management of parasitic weeds. PMID- 22323400 TI - Reversal of diabetes by betaTC3 cells encapsulated in alginate beads generated by emulsion and internal gelation. AB - Encapsulation of insulin-producing cells in alginate beads could improve the treatment of type 1 diabetes by reducing or eliminating the need for immunosuppression. We have recently adapted an emulsion and internal gelation process to beta-cell encapsulation. This process has the advantages of being well suited for m(3)/h production rates and allowing the use of increased alginate concentrations. Compared with 1.5% alginate beads generated by a standard extrusion process, 5% alginate emulsion-generated beads demonstrated greater in vitro stability and greater volumetric exclusion of antibody-sized pullulan. When betaTC3 cells were transplanted into streptozotocin-induced allogeneic diabetic mice, a significant decrease in the blood glucose levels was seen within 2 days with the 5% emulsion-generated beads but not until >16 days with the 1.5% extrusion-generated beads. This was correlated with higher cell survival and lower graft-specific plasma immunoglobulin levels. These results suggest that higher-concentration alginate beads generated by emulsion and internal gelation have improved graft immunoprotection. The emulsion process is a promising and scalable technology for cellular therapies requiring immune isolation. PMID- 22323401 TI - Improving the robustness of a low-cost insect cell medium for baculovirus biopesticides production, via hydrolysate streamlining using a tube bioreactor based statistical optimization routine. AB - A critical component of an in vitro production process for baculovirus biopesticides is a growth medium that is efficacious, robust, and inexpensive. An in-house low-cost serum-free medium, VPM3, has been shown to be very promising in supporting Helicoverpa armigera nucleopolyhedrovirus (HaSNPV) production in H. zea insect cell suspension cultures, for use as a biopesticide against the Heliothine pest complex. However, VPM3 is composed of a significant number of undefined components, including five different protein hydrolysates, which introduce a challenging lot-to-lot variability to the production process. In this study, an intensive statistical optimization routine was employed to reduce the number of protein hydrolysates in VPM3 medium. Nearly 300 runs (including replicates) were conducted with great efficiency by using 50 mL TubeSpin(r) bioreactors to propagate insect cell suspension cultures. Fractional factorial experiments were first used to determine the most important of the five default protein hydrolysates, and to screen for seven potential substitutes for the default meat peptone, Primatone RL. Validation studies informed by the screening tests showed that promising alternative media could be formulated based on just two protein hydrolysates, in particular the YST-AMP (Yeast Extract and Amyl Meat Peptone) and YST-POT (Yeast Extract and Lucratone Potato Peptone) combinations. The YST-AMP (meat-based) and YST-POT (meat-free) variants of VPM3 were optimized using response surface methodology, and were shown to be just as good as the default VPM3 and the commercial Sf-900 II media in supporting baculovirus yields, hence providing a means toward a more reproducible and scalable production process for HaSNPV biopesticides. PMID- 22323402 TI - Interaction between saflufenacil and imazethapyr in red rice (Oryza ssp.) and hemp sesbania (Sesbania exaltata) as affected by light intensity. AB - BACKGROUND: Saflufenacil is a broadleaf herbicide for preplant burndown and pre emergence applications in various crops. This study was established to evaluate the absorption and translocation of saflufenacil in hemp sesbania and imazethapyr in red rice as a function of their post-emergence interaction and light intensity. RESULTS: Imazethapyr plus saflufenacil provided a greater uptake (30%) and translocation (35%) of (14) C-imazethapyr than imazethapyr alone. In the section above treated leaf (ATL), a higher percentage of the absorbed imazethapyr (23%) was quantified in the imazethapyr plus saflufenacil treatment after 168 h. Faster basipetal movement of imazethapyr was identified under higher light availability. Absorption of (14) C-saflufenacil ranged from approximately 40 to 60% among herbicide and light intensity treatments. At 12 and 24 h after treatment (HAT) a greater percentage (15-20%) of the absorbed saflufenacil was quantified above the treated leaf at the two lower light intensities. Similar trends were observed for basipetal movement of saflufenacil. CONCLUSION: Saflufenacil enhanced absorption, overall translocation and acropetal movement of imazethapyr in the TX4 red rice. Basipetal movement of imazethapyr was faster under higher light intensities. Overall, imazethapyr improved absorption of saflufenacil in hemp sesbania plants. Reduction in light intensity resulted in greater translocation of saflufenacil, promoting acropetal and basipetal distribution at the two lower light intensity treatments. PMID- 22323404 TI - A new target for myeloma therapy. AB - In this issue of Blood, Azab and colleagues demonstrate that PSGL-1 expressed on myeloma cells is involved with regulating tumor cell extravasation, homing, disease progression, and drug resistance. PMID- 22323403 TI - Seasonal variation of chemical species associated with short-term mortality effects of PM(2.5) in Xi'an, a Central City in China. AB - The authors conducted a time-series analysis to examine seasonal variation of mortality risk in association with particulate matter less than 2.5 MUm in aerodynamic diameter (PM(2.5)) and chemical species in Xi'an, China, using daily air pollution and all-cause and cause-specific mortality data (2004-2008). Poisson regression incorporating natural splines was used to estimate mortality risks of PM(2.5) and its chemical components, adjusting for day of the week, time trend, and meteorologic effects. Increases of 2.29% (95% confidence interval: 0.83, 3.76) for all-cause mortality and 3.08% (95% confidence interval: 0.94, 5.26) for cardiovascular mortality were associated with an interquartile range increase of 103.0 MUg/m(3) in lagged 1-2 day PM(2.5) exposure. Stronger effects were observed for the elderly (>=65 years), males, and cardiovascular diseases groups. Secondary components (sulfate and ammonium), combustion species (elemental carbon, sulfur, chlorine), and transition metals (chromium, lead, nickel, and zinc) appeared most responsible for increased risk, particularly in the cold months. The authors concluded that differential association patterns observed across species and seasons indicated that PM(2.5)-related effects might not be sufficiently explained by PM(2.5) mass alone. Future research is needed to examine spatial and temporal varying factors that might play important roles in modifying the PM(2.5)-mortality association. PMID- 22323405 TI - Getting rid of refractory hemophilia. AB - In a prospective randomized, multicenter study of immune tolerance induction(ITI) in patients with hemophilia A refractory to replacement therapy after the development of alloantibodies that inhibit factor VIII (FVIII) activity, Hay and DiMichele compared two regimens, a low dose of FVIII (50 IU/Kg thrice weekly)or a high-dose (200 IU/kg daily PMID- 22323406 TI - When IFN interferes with cell fate. AB - In this issue of Blood, de Bruin and colleagues demonstrate the ability of IFN gamma to influence the binary cell fate choices of granulocytic-monocytic progenitors(GMPs) during viral infection, favoring monocytic over the granulocytic differentiation. This work provides mechanistic insights and a better understanding on how hematopoiesis can be remodeled during infection PMID- 22323407 TI - High VWF, low ADAMTS13 puts women at risk. AB - In this issue of Blood, Andersson and colleagues reveal in a case-control study that highVWF and low ADAMTS13 plasma levels are each a risk factor for ischemic stroke and myocardial infarction, and that the combination of both results in a joint effect. PMID- 22323408 TI - Tolerant heaven or mHEL trouble. AB - In this issue of Blood, Smith and colleagues find that an RBC transfusion can induce tolerance to the foreign antigens on the surface of transfused erythrocytes if the animal has not been given an inflammatory stimulus. PMID- 22323409 TI - Exciting new murine model of cGVHD. AB - In this issue of Blood, Srinivasan et al report that mice conditioned for allogeneic hematopoietic stem cell transplantation with cyclophosphamide and total body irradiation develop wide-spectrum manifestations of chronic graft versus-host disease (cGVHD).1 This represents an exciting new preclinical model that can be used to uncover mechanisms of cGVHD and test interventional therapies. PMID- 22323410 TI - Plasma 25-hydroxyvitamin D and progression to diabetes in patients at risk for diabetes: an ancillary analysis in the Diabetes Prevention Program. AB - OBJECTIVE: To investigate the association between vitamin D status, assessed by plasma 25-hydroxyvitamin D, and risk of incident diabetes. RESEARCH DESIGN AND METHODS: Prospective observational study with a mean follow-up of 2.7 years in the Diabetes Prevention Program (DPP), a multicenter trial comparing different strategies for prevention of diabetes in patients with prediabetes. We assessed the association between plasma 25-hydroxyvitamin D, measured repeatedly during follow-up, and incident diabetes in the combined placebo (n = 1,022) and intensive lifestyle (n = 1,017) randomized arms of the DPP. Variables measured at multiple study time points (25-hydroxyvitamin D, BMI, and physical activity) entered the analyses as time-varying "lagged" covariates, as the mean of the previous and current visits at which diabetes status was assessed. RESULTS: After multivariate adjustment, including for the DPP intervention, participants in the highest tertile of 25-hydroxyvitamin D (median concentration, 30.1 ng/mL) had a hazard ratio of 0.72 (95% CI 0.56-0.90) for developing diabetes compared with participants in the lowest tertile (median concentration, 12.8 ng/mL). The association was in the same direction in placebo (0.70; 0.52-0.94) versus lifestyle arm (0.80; 0.54-1.17). CONCLUSIONS: Higher plasma 25-hydroxyvitamin D, assessed repeatedly, was associated with lower risk of incident diabetes in high risk patients, after adjusting for lifestyle interventions (dietary changes, increased physical activity, and weight loss) known to decrease diabetes risk. Because of the observational nature of the study, the potential association between vitamin D and diabetes needs to be confirmed in intervention studies. PMID- 22323411 TI - Absence of disparities in the quality of primary diabetes care for South Asians and Chinese in an urban Canadian setting. AB - OBJECTIVE: To examine whether quality of diabetes care is equitable for South Asian and Chinese patients in an urban Canadian setting. RESEARCH DESIGN AND METHODS: Process and intermediate measures of quality of care were compared between 246 South Asians, 170 Chinese, and 431 patients from the general population with type 2 diabetes selected from 45 family physicians' practices. RESULTS: A total of 61% of Chinese achieved A1C <=7.0% versus 45% of South Asians and 49% of the general population (P < 0.05). They were also more likely to achieve LDL cholesterol <=2.0 mmol/L, while South Asians were more likely to achieve blood pressure <=130/80. There was only one significant process of care deficiency: fewer foot examinations among South Asians (34 vs. 49% for the general population, P < 0.01). CONCLUSIONS: Quality of diabetes care in a Canadian urban setting was equitable, with ethnic minorities somewhat more likely to achieve recommended targets than the general population. PMID- 22323412 TI - Detection of diabetic sensorimotor polyneuropathy by corneal confocal microscopy in type 1 diabetes: a concurrent validity study. AB - OBJECTIVE: We aimed to determine the corneal confocal microscopy (CCM) parameter that best identifies diabetic sensorimotor polyneuropathy (DSP) in type 1 diabetes and to describe its performance characteristics. RESEARCH DESIGN AND METHODS: Concurrent with clinical and electrophysiological examination for classification of DSP, CCM was performed on 89 type 1 diabetic and 64 healthy subjects to determine corneal nerve fiber length (CNFL), density, tortuosity, and branch density. Area under the curve (AUC) and optimal thresholds for DSP identification in those with diabetes were determined by receiver operating characteristic (ROC) curve analysis. RESULTS: DSP was present in 33 (37%) subjects. With the exception of tortuosity, CCM parameters were significantly lower in DSP case subjects. In ROC curve analysis, AUC was greatest for CNFL (0.88) compared with fiber density (0.84, P = 0.0001), branch density (0.73, P < 0.0001), and tortuosity (0.55, P < 0.0001). The threshold value that optimized sensitivity and specificity for ruling in DSP was a CNFL of <=14.0 mm/mm(2) (sensitivity 85%, specificity 84%), associated with positive and negative likelihood ratios of 5.3 and 0.18. An alternate approach that used separate threshold values maximized sensitivity (threshold value >=15.8 mm/mm(2), sensitivity 91%, negative likelihood ratio 0.16) and specificity (<=11.5 mm/mm(2), specificity 93%, positive likelihood ratio 8.5). CONCLUSIONS: Among CCM parameters, CNFL best discriminated DSP cases from control subjects. A single threshold offers clinically acceptable operating characteristics, although a strategy that uses separate thresholds to respectively rule in and rule out DSP has excellent performance while minimizing unclassified subjects. We hypothesize that values between these thresholds indicate incipient nerve injury that represents those individuals at future neuropathy risk. PMID- 22323413 TI - Spuriously high prevalence of prediabetes diagnosed by HbA(1c) in young indians partly explained by hematological factors and iron deficiency anemia. AB - OBJECTIVE: To examine the influence of glycemic and nonglycemic parameters on HbA(1c) concentrations in young adults, the majority of whom had normal glucose tolerance. RESEARCH DESIGN AND METHODS: We compared the diagnosis of normal glucose tolerance, prediabetes, and diabetes between a standard oral glucose tolerance test (OGTT; World Health Organization 2006 criteria) and HbA(1c) concentrations (American Diabetes Association [ADA] 2009 criteria) in 116 young adults (average age 21.6 years) from the Pune Children's Study. We also studied the contribution of glycemic and nonglycemic determinants to HbA(1c) concentrations. RESULTS: The OGTT showed that 7.8% of participants were prediabetic and 2.6% were diabetic. By ADA HbA(1c) criteria, 23.3% were prediabetic and 2.6% were diabetic. The negative predictive value of HbA(1c) was 93% and the positive predictive value was 20% (only 20% had prediabetes or diabetes according to the OGTT; this figure was 7% in anemic participants). Of participants, 34% were anemic, 37% were iron deficient (ferritin <15 ng/mL), 40% were vitamin B(12) deficient (<150 pmol/L), and 22% were folate deficient (<7 nmol/L). On multiple linear regression analysis, HbA(1c) was predicted by higher 2-h glucose (R(2) = 25.6%) and lower hemoglobin (R(2) = 7.7%). When hematological parameters were replaced by ferritin, vitamin B(12), and folate, HbA(1c) was predicted by higher glycemia (R(2) = 25.6%) and lower ferritin (R(2) = 4.3%). CONCLUSIONS: The use of HbA(1c) to diagnose prediabetes and diabetes in iron deficient populations may lead to a spuriously exaggerated prevalence. Further investigation is required before using HbA(1c) as a screening tool in nutritionally compromised populations. PMID- 22323415 TI - Infant and toddler type 1 diabetes: complications after 20 years' duration. AB - OBJECTIVE: To compare the effect of the prepubertal duration of diabetes on the occurrence of complications in two groups of patients after the same number of years of the disease. RESEARCH DESIGN AND METHODS: This multicenter study enrolled 105 patients aged 16-40.3 years; 53 were prepubertal at diagnosis (aged 0-3) and 52 were pubertal (Tanner stage) and aged 9-14.9. The mean duration of disease was 19.8 and 19.5 years for prepubertal and pubertal patients, respectively. In all patients, retinal photographs were taken and centrally graded. Urinary albumin excretion (UAE; 86 case subjects), blood pressure (BP; 89 case subjects), and lifetime HbA(1c) (72 case subjects) were also evaluated. RESULTS: The prevalence of diabetic retinopathy (DR) was higher in pubertal than in prepubertal patients, both for any grade DR (71 vs. 40%, P = 0.002) and for mild or more severe DR (P = 0.005). The prevalence of abnormal UAE was not different in the two groups. Hypertension was found only in three patients, all pubertal at diagnosis. In the small group with moderate-to-severe DR, lifetime HbA(1c) levels, as percentages above the upper normal reference value, were higher (P < 0.01) in prepubertal than in pubertal patients. CONCLUSIONS: If diabetes is diagnosed in infants or toddlers and the prepubertal duration of diabetes is very long, the patients seem to be protected against DR. This protection disappears if lifetime metabolic control is bad. Instead, when onset is at puberty, the DR risk is higher and less dependent on metabolic control and may be influenced by age-related factors, such as BP. PMID- 22323414 TI - Achievement of target A1C levels with negligible hypoglycemia and low glucose variability in youth with short-term type 1 diabetes and residual beta-cell function. AB - OBJECTIVE: To determine exposure to hyper- and hypoglycemia using blinded continuous glucose monitoring (CGM) profiles in youth with type 1 diabetes (T1D) with residual beta-cell function during the first year of insulin treatment. RESEARCH DESIGN AND METHODS: Blinded, 3-7 day CGM profiles were obtained in 16 short-term T1D patients (age 8-18 years, T1D duration 6-52 weeks) who had peak C peptide levels ranging from 0.46 to 1.96 nmol/L during a mixed-meal tolerance test. Results in this short-term group were compared with those in 34 patients with well-controlled, longer-term T1D (duration >=5 years), matched for age and A1C with the short-term T1D group, and with those in 26 age-matched nondiabetic individuals. RESULTS: Despite matching for A1C, and therefore similar mean sensor glucose levels in the two T1D groups, short-term T1D participants had a lower frequency of hypoglycemia (0.3 vs. 7.6%, P < 0.001), a trend toward less hyperglycemia (17 vs. 32%, P = 0.15), and a greater percentage in the target range (median 77 vs. 60%, P = 0.02). Indeed, the percentage of sensor glucose levels <=70 mg/dL in the short-term T1D group (0.3%) did not differ from those in the nondiabetic group (1.7%, P = 0.73). The coefficient of variation of sensor glucose levels (an index of glucose variability) was lower in short-term vs. longer-term T1D participants (27 vs. 42%, respectively, P < 0.001). CONCLUSIONS: In youth with short-term T1D who retain residual beta-cell function, there is negligible exposure to hypoglycemia and lower glucose variability than in youth with well-controlled T1D of longer duration. PMID- 22323416 TI - Relationship between A1C and fasting plasma glucose in dysglycemia or type 2 diabetes: an analysis of baseline data from the ORIGIN trial. AB - OBJECTIVE: A1C measurement has advantages over measures of plasma glucose. Few studies have evaluated the A1C-fasting plasma glucose (FPG) relationship and whether oral antidiabetes drugs (OADs) and ethnic or geographic variations affect the relationship. Baseline A1C and FPG data from the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial participants were analyzed to 1) elucidate the relationship between A1C and FPG in people with moderate dysglycemia (A1C 5.6-9.0% [38-75 mmol/mol]) and additional risk factors for cardiovascular disease, 2) determine whether this relationship is altered by use of an OAD, and 3) study whether geographic and ethnic differences exist. RESEARCH DESIGN AND METHODS: Analysis was performed of 12,527 participants with dysglycemia or early type 2 diabetes recruited in North America, South America, Europe, Australia, and Asia who comprised white, Latin American, Asian, black, and other ethnicities. The A1C-FPG relationships were analyzed using cubic B spline curves in all participants and in subgroups not using an OAD or using an OAD and comprising persons of different ethnic or geographic origin. RESULTS: A strong relationship between FPG in the range of 5.6-9.0 mmol/L and the corresponding A1C was seen across different geographic regions and ethnic groups. A smaller increase in A1C per unit increase in FPG occurred for persons taking an OAD versus those not taking an OAD. CONCLUSIONS: The strong relationship between A1C and FPG in moderate dysglycemia is not significantly affected by ethnic or geographic differences. Use of an OAD alters the relationship and should be considered when interpreting A1C level. PMID- 22323417 TI - Prevalence of diabetes and intermediate hyperglycemia among adults from the first multinational study of noncommunicable diseases in six Central American countries: the Central America Diabetes Initiative (CAMDI). AB - OBJECTIVE: The increasing burdens of obesity and diabetes are two of the most prominent threats to the health of populations of developed and developing countries alike. The Central America Diabetes Initiative (CAMDI) is the first study to examine the prevalence of diabetes in Central America. RESEARCH DESIGN AND METHODS: The CAMDI survey was a cross-sectional survey based on a probabilistic sample of the noninstitutionalized population of five Central American populations conducted between 2003 and 2006. The total sample population was 10,822, of whom 7,234 (67%) underwent anthropometry measurement and a fasting blood glucose or 2-h oral glucose tolerance test. RESULTS: The total prevalence of diabetes was 8.5%, but was higher in Belize (12.9%) and lower in Honduras (5.4%). Of the screened population, 18.6% had impaired glucose tolerance/impaired fasting glucose. CONCLUSIONS: As this population ages, the prevalence of diabetes is likely to continue to rise in a dramatic and devastating manner. Preventive strategies must be quickly introduced. PMID- 22323418 TI - The application of a crosslinked pectin-based wafer matrix for gradual buccal drug delivery. AB - The purpose of this study was to develop crosslinked wafer matrices and establish the influence of the crosslinker type and processing sequence on achieving gradual buccal drug delivery. Three sets of drug-loaded crosslinked pectin wafers were produced employing the model water-soluble antihistamine, diphenhydramine and were compared with noncrosslinked wafers. The formulations were crosslinked with CaCl(2), BaCl(2), or ZnSO(4) pre- or postlyophilization (sets 1 and 2) as well as pre- and postlyophilization (set 3), respectively. The surface morphology, porositometry, molecular vibrational transitions, textural attributes, thermal and in vitro drug release were characterized and supported by in silico molecular mechanics simulations. Results revealed that crosslinked wafers produced smaller pore sizes (107.63 A) compared with noncrosslinked matrices (180.53 A) due to molecular crosslinks formed between pectin chains. Drug release performance was dependent on the wafer crosslinking production sequence. Noncrosslinked wafers displayed burst-release with 82% drug released at t(30min) compared with first-order kinetic profiles obtained for prelyophilized crosslinked matrices (50% released at t(30min) followed by steady release). Wafers crosslinked postlyophilization displayed superior control of drug release (40% at t(30min)). Molecular mechanics simulations corroborated with the experimental data and established that Ba(++), having the largest atomic radii (1.35 A) formed a number of ionic bridges producing wafers of higher porosity (0.048 cm(2)/g) and had more influence on drug release. PMID- 22323419 TI - White matter abnormalities in children and adolescents with obsessive-compulsive disorder: a diffusion tensor imaging study. AB - BACKGROUND: There is paucity of data on white matter (WM) abnormalities in juvenile obsessive-compulsive disorder (OCD). This study aimed to identify WM microstructure changes in juvenile OCD. METHODS: Fifteen children and adolescents with OCD and 15 matched healthy controls underwent diffusion tensor imaging using a 3 Tesla (Achieva, Best, The Netherlands) magnetic resonance imaging scanner. Voxelwise analyses were conducted on data processed through tract-based spatial statistics (TBSS). RESULTS: Patients significantly differed from controls in axial as well as radial diffusivities, but not in fractional anisotropy. Patients demonstrated significantly increased axial diffusivity in corpus callosum (genu, body, and splenium), right and left superior longitudinal fasciculi, left inferior longitudinal fasciculus, right and left cingulum, bilateral anterior thalamic radiations, bilateral anterior limb of internal capsule, left posterior limb of the internal capsule, and middle cerebellar peduncle. In addition, significantly increased radial diffusivity was seen in patients in genu of the corpus, right and left superior longitudinal fasciculi, left inferior longitudinal fasciculus, right and left uncinate fasciculi, bilateral anterior thalamic radiation, bilateral inferior fronto-occipital fasciculus, left posterior limb of internal capsule, right superior cerebellar peduncle, middle cerebellar peduncle, and right inferior cerebellar peduncle. CONCLUSIONS: Our findings suggest involvement of multiple WM tracts in juvenile OCD. In addition to the widely proposed hypothesis of orbitofrontal-striato-thalamo-cortical circuitry deficits in the development of OCD, our findings suggest involvement of additional brain regions, possibly parietal cortex, lateral prefrontal cortex, and limbic system. The widespread differences in WM among cases and controls also points to the possibility of underlying myelination changes. PMID- 22323420 TI - Hepatocellular carcinoma and model for end-stage liver disease exceptions: the more we understand, the more challenging the allocation gets. PMID- 22323421 TI - Rapidly progressive colonic dysplasia/neoplasia in a series of treated lung cancer patients: Is paclitaxel involved? AB - Incidence of second malignancies in patients with advanced lung cancer is not well-studied, in part because of a short survival in this patient population. Apart from a genetic predisposition, various environmental hazards may also be at play in their pathogenesis. Chronic smoking exposure decreases T-cell responsiveness and stimulates production of a variety of inhibitory cytokines. Paclitaxel has been associated with several immunosuppressive effects such as decreased numbers and activity of dendritic cells, NK-cells, and monocytes. We herein describe the first series of lung cancer patients who developed colonic polyps/colon cancer either during or immediately following chemotherapy with paclitaxel, suggesting a possible role of this agent in their pathogenesis. PMID- 22323422 TI - Successful rechallenge after ixabepilone-induced radiation recall dermatitis using an alternative dosing strategy. AB - Radiation recall dermatitis (RRD) is an inflammatory reaction occurring in a previously irradiated area, precipitated by the administration of certain drugs. The drugs most commonly associated with RRD are intravenous antineoplastic agents. The frequency of development of this toxicity in clinical practice is unclear. We report a case of RRD induced by ixabepilone, an epothilone antineoplastic agent, with successful rechallenge utilizing an alternative dosing regimen. PMID- 22323423 TI - Design and self-assembly of a leucine-enkephalin analogue in different nanostructures: application of nanovesicles. AB - An opioid (leucine-enkephalin) conformational analogue forms diverse nanostructures such as vesicles, tubes, and organogels through self-assembly. The nanovesicles encapsulate the natural hydrophobic drug curcumin and allow the controlled release through cation-generated porogens in membrane mimetic solvent. PMID- 22323424 TI - Asymptotic properties of mean survival estimate based on the Kaplan-Meier curve with an extrapolated tail. AB - Asymptotic distribution of the mean survival time based on the Kaplan-Meier curve with an extrapolated 'tail' is derived. A closed formula of the variance estimate is provided. Asymptotic properties of the estimator were studied in a simulation study, which showed that this estimator was unbiased with proper coverage probability and followed a normal distribution. An example is used to demonstrate the application of this estimator. PMID- 22323425 TI - A strong electronic coupling between graphene nanosheets and layered titanate nanoplates: a soft-chemical route to highly porous nanocomposites with improved photocatalytic activity. AB - Strongly coupled nanocomposites of layered titanate and reduced graphene oxide (RGO) are synthesized by electrostatically derived self-assembly between negatively charged RGO nanosheets and positively charged TiO(2) nanosols, which is then followed by a phase transition of the anatase TiO(2) component into layered titanate. The resulting nanocomposite consists of thin 2D nanoplates of lepidocrocite-type layered titanate immobilized on the surface of RGO nanosheets. The composite formation with RGO nanosheets is effective not only in promoting the phase transition of anatase TiO(2) nanosols, but also in improving the thermal stability of the layered titanate, indicating the role of RGO nanosheets as an agent for directing and stabilizing layered structures. The layered titanate-RGO nanocomposites exhibit remarkably expanded surface area with the formation of micropores and mesopores. The composite formation with RGO nanosheets gives rise to the disappearance of the reflectance edge of layered titanate in the diffuse reflectance UV-vis spectra, indicating a strong electronic coupling between the RGO and layered titanate. The strong electronic correlation between the two components is further evidenced by the visible-light induced generation of photocurrents after the hybridization with RGO. The layered titanate-RGO nanocomposite shows a higher activity for the photodegradation of organic molecules than uncomposited layered titanate, underscoring the usefulness of graphene hybridization in improving the photocatalyst performance of layered titanate. The experimental findings presented here clearly demonstrate that the self-assembly of metal oxide nanoparticles with RGO 2D nanosheets is quite effective not only in synthesizing porous metal-oxide-graphene nanocomposites with improved photo-induced functionality, but also in achieving strong electronic coupling between RGO and metal oxides. PMID- 22323426 TI - Porous crosslinked poly(epsilon-caprolactone fumarate)/nanohydroxyapatite composites for bone tissue engineering. AB - Porous nanocomposites based on poly(epsilon-caprolactone fumarate) (PCLF) resin matrix; N-vinyl pyrrolidone (NVP) as a reactive diluents and nanohydroxyapatite (nHA) filler were developed for bone tissue engineering applications. Nanocomposite scaffolds with three different contents of nHA [5, 10, and 20 (w/w %)] were prepared by thermal crosslinking of PCLF followed by particulate leaching and characterized in terms of mechanical properties (cyclic loading) and in vitro cell-material interaction by MTT assay and alkaline phosphatase activity measurements. Five osteoblastic cell lines were used to investigate the ability of the nanocomposites to support cell attachment, spreading, and proliferation after 3, 7, and 14 days. By adding the nHA filler phase, elastic modulus of the nanocomposites increased significantly. Scaffolds showed comparable biocompatibility to neat nHA particles, commercial bone graft (Bio-Oss) and tissue culture polystyrene as control groups. According to the results it can be concluded that these scaffolds are potential candidates for bone substitution because of their mechanical strength and bioactivity. PMID- 22323427 TI - Diverse spore rains and limited local exchange shape fern genetic diversity in a recently created habitat colonized by long-distance dispersal. AB - BACKGROUND AND AIMS: Populations established by long-distance colonization are expected to show low levels of genetic variation per population, but strong genetic differentiation among populations. Whether isolated populations indeed show this genetic signature of isolation depends on the amount and diversity of diaspores arriving by long-distance dispersal, and time since colonization. For ferns, however, reliable estimates of long-distance dispersal rates remain largely unknown, and previous studies on fern population genetics often sampled older or non-isolated populations. Young populations in recent, disjunct habitats form a useful study system to improve our understanding of the genetic impact of long-distance dispersal. METHODS: Microsatellite markers were used to analyse the amount and distribution of genetic diversity in young populations of four widespread calcicole ferns (Asplenium scolopendrium, diploid; Asplenium trichomanes subsp. quadrivalens, tetraploid; Polystichum setiferum, diploid; and Polystichum aculeatum, tetraploid), which are rare in The Netherlands but established multiple populations in a forest (the Kuinderbos) on recently reclaimed Dutch polder land following long-distance dispersal. Reference samples from populations throughout Europe were used to assess how much of the existing variation was already present in the Kuinderbos. KEY RESULTS: A large part of the Dutch and European genetic diversity in all four species was already found in the Kuinderbos. This diversity was strongly partitioned among populations. Most populations showed low genetic variation and high inbreeding coefficients, and were assigned to single, unique gene pools in cluster analyses. Evidence for interpopulational gene flow was low, except for the most abundant species. CONCLUSIONS: The results show that all four species, diploids as well as polyploids, were capable of frequent long-distance colonization via single-spore establishment. This indicates that even isolated habitats receive dense and diverse spore rains, including genotypes capable of self-fertilization. Limited gene flow may conserve the genetic signature of multiple long-distance colonization events for several decades. PMID- 22323429 TI - Synthesis and identification of metastable compounds: black arsenic--science or fiction? PMID- 22323428 TI - Foundation characteristics of edible Musa triploids revealed from allelic distribution of SSR markers. AB - BACKGROUND AND AIMS: The production of triploid banana and plantain (Musa spp.) cultivars with improved characteristics (e.g. greater disease resistance or higher yield), while still preserving the main features of current popular cultivars (e.g. taste and cooking quality), remains a major challenge for Musa breeders. In this regard, breeders require a sound knowledge of the lineage of the current sterile triploid cultivars, to select diploid parents that are able to transmit desirable traits, together with a breeding strategy ensuring final triploidization and sterility. Highly polymorphic single sequence repeats (SSRs) are valuable markers for investigating phylogenetic relationships. METHODS: Here, the allelic distribution of each of 22 SSR loci across 561 Musa accessions is analysed. KEY RESULTS AND CONCLUSIONS: We determine the closest diploid progenitors of the triploid 'Cavendish' and 'Gros Michel' subgroups, valuable information for breeding programmes. Nevertheless, in establishing the likely monoclonal origin of the main edible triploid banana subgroups (i.e. 'Cavendish', 'Plantain' and 'Mutika-Lujugira'), we postulated that the huge phenotypic diversity observed within these subgroups did not result from gamete recombination, but rather from epigenetic regulations. This emphasizes the need to investigate the regulatory mechanisms of genome expression on a unique model in the plant kingdom. We also propose experimental standards to compare additional and independent genotyping data for reference. PMID- 22323430 TI - Influence of the shape of nanostructured metal surfaces on adsorption of single peptide molecules in aqueous solution. AB - Self-assembly and function of biologically modified metal nanostructures depend on surface-selective adsorption; however, the influence of the shape of metal surfaces on peptide adsorption mechanisms has been poorly understood. The adsorption of single peptide molecules in aqueous solution (Tyr(12) , Ser(12) , A3, Flg-Na(3) ) is investigated on even {111} surfaces, stepped surfaces, and a 2 nm cuboctahedral nanoparticle of gold using molecular dynamics simulation with the CHARMM-METAL force field. Strong and selective adsorption is found on even surfaces and the inner edges of stepped surfaces (-20 to -60 kcal/mol peptide) in contrast to weaker and less selective adsorption on small nanoparticles (-15 to 25 kcal/mol peptide). Binding and selectivity appear to be controlled by the size of surface features and the extent of co-ordination of epitaxial sites by polarizable atoms (N, O, C) along the peptide chain. The adsorption energy of a single peptide equals a fraction of the sum of the adsorption energies of individual amino acids that is characteristic of surface shape, epitaxial pattern, and conformation constraints (often beta-strand and random coil). The proposed adsorption mechanism is supported and critically evaluated by earlier sequence data from phage display, dissociation constants of small proteins as a function of nanoparticle size, and observed shapes of peptide-stabilized nanoparticles. Understanding the interaction of single peptides with shaped metal surfaces is a key step towards control over self-organization of multiple peptides on shaped metal surfaces and the assembly of superstructures from nanostructures. PMID- 22323432 TI - Effects of the stationary phase and the solvent on the stereodynamics of biphep ligands quantified by dynamic three-column HPLC. PMID- 22323431 TI - Analysis of miniature single- and double-notch bending specimens for estimating the fracture toughness of cortical bone. AB - Studies of the fracture behavior of cortical bone have determined multiple toughening mechanisms that are active during propagation of a crack. Common methods for measuring bone fracture toughness use single-notched specimens often in four-point (SN4PB) or three-point bending (SN3PB). A double-notch four-point bending (DN4PB) specimen is useful to study prefailure damage at the crack tip. Total failure occurs at one notch and only partial failure at the other allowing study of prefailure damage in the unbroken notch. There is no widely known method for calculating the fracture toughness of bone using a DN4PB specimen. A method for calculating the fracture toughness of cortical bone using a DN4PB is developed here and compared with results for a common SN3PB specimen. The new double-notch method permits using a single specimen to measure apparent fracture toughness and to study both pre- and postfailure microdamage in the bone matrix. When and how to use the new and the established test specimens for understanding bone mechanics is discussed. PMID- 22323433 TI - Snoring management with nasal surgery and upper airway radiofrequency ablation. AB - OBJECTIVE: To review techniques and outcomes of nasal surgery with upper airway radiofrequency ablation (RFA) when used for socially disruptive snoring, including the rate of infection with reused RFA applicator tips. STUDY DESIGN: Case series with chart review. SETTING: Community-based sleep-disordered breathing clinic. METHODS: A prospectively acquired sleep quality assurance database was reviewed to determine demographics, complications, snoring outcomes, level of daytime sleepiness, and sleep-related quality of life in patients with socially disruptive snoring treated with nasal surgery and upper airway RFA. RESULTS: One hundred thirty patients (48 women; 82 men) with a mean age of 50 years (range, 24-83 years) underwent nasal surgery and upper airway RFA for the treatment of chronic nasal blockage with socially disruptive snoring. All patients underwent septoplasty with or without inferior turbinate reduction and RFA to the soft palate and/or base of tongue. Patients received a mean of 2.2 (range, 1-4) applications of upper airway RFA during the course of treatment. No infections occurred with reuse of applicator tips. Fifty-four bed partners (42%) reported complete snoring resolution, whereas 68 (52%) reported residual snoring that was improved. Snoring resolution was more common in patients who underwent repeated applications of upper airway RFA (odds ratio 2.39; 95% confidence interval, 1.09-5.26). CONCLUSION: Nasal surgery combined with upper airway RFA improved snoring with few complications in this series of patients with anatomic nasal obstruction with socially disruptive snoring. Reuse of RFA applicator tips at palatal sites reduces cost without an observed increase in the risk of upper airway infection. PMID- 22323434 TI - Cyclin D1 and FADD as biomarkers in head and neck squamous cell carcinoma. AB - OBJECTIVE: Cyclin D1 and FADD (Fas-associated protein with death domain) regulate the cell cycle and apoptosis, respectively, and are located on chromosome 11q13, which is frequently amplified in head and neck squamous cell carcinoma (HNSCC). This study evaluates these proteins as predictors of clinical outcomes for HNSCC. STUDY DESIGN: Historical cohort study. SETTING: Academic tertiary care center. SUBJECTS: Two hundred twenty-two patients with upper aerodigestive HNSCC. RESULTS: Patients with tumors that were strongly positive for cyclin D1 and FADD had reduced overall (OS; P = .003 and P < .001), disease-specific (DSS; P = .039 and P < .001), and disease-free (DFS; P = .026 and P < .001) survival, respectively. Together, the 2 markers effectively stratified OS (P < .001), DSS (P < .001), and DFS (P = .002). Strong FADD staining correlated with greater alcohol consumption and varied significantly with primary tumor site: 56% of hypopharynx tumors expressed high levels of FADD but only 7% of glottis tumors. Using Cox regression analysis, FADD and N stage were significant independent predictors of DSS and DFS, whereas cyclin D1, FADD, and N stage were independently significant for OS. CONCLUSION: Cyclin D1 and FADD may have utility as predictors of long-term outcomes for patients with HNSCC. Further study is needed to determine if these proteins predict response to different treatment approaches or assist in selecting patients for multimodality therapy. PMID- 22323435 TI - Microbubble therapy enhances anti-tumor properties of cisplatin and cetuximab in vitro and in vivo. AB - OBJECTIVE: To determine if microbubble-mediated ultrasound therapy (MB-UST) can improve cisplatin or cetuximab cytotoxicity of head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo by increasing tumor-specific drug delivery by disruption of tumor cell membranes and enhancing vascular permeability. STUDY DESIGN: In vitro and in vivo study. SETTING: University medical center. SUBJECTS: Immunodeficient mice (6 weeks old) and 4 HNSCC cell lines. METHODS: Changes to cell permeability were assessed in vitro after MB-UST. Cellular apoptosis resulting from adjuvant MB-UST with subtherapeutic doses of cisplatin or cetuximab was assessed by cell survival assays in vitro. The in vivo effect of adjuvant MB-UST in flank tumors was assessed in vivo with histological analysis and diffusion-weighted magnetic resonance imaging (DW-MRI). RESULTS: In vitro results revealed that MB-UST can increase cell permeability and enhance drug uptake and apoptosis in 4 HNSCC cell lines. In vivo adjuvant MB-UST with cetuximab or cisplatin showed a statistically significant reduction in tumor size when compared with untreated controls. TUNEL analysis yielded a larger number of cells undergoing apoptosis in tumors treated with cetuximab and adjuvant MB-UST than did cetuximab alone but was not significantly greater in tumors treated with cisplatin and adjuvant MB-UST compared with cisplatin alone. DW-MRI analysis showed more free water, which corresponds to increased cell membrane disruption, in tumors treated with MB-UST. CONCLUSION: MB-UST promotes disruption of cell membranes in tumor cells in vitro, which may be leveraged to selectively improve the uptake of conventional and targeted therapeutics in vivo. PMID- 22323437 TI - DNA-length-dependent fluorescence signaling on graphene oxide surface. AB - Fluorescence energy transfer to graphene oxide is studied using covalently linked DNA probes ranging from 4 to 70 base pairs. The characteristic distance and mechanism of energy transfer are reported. PMID- 22323436 TI - Effect of radiation therapy on survival in surgically resected retroperitoneal sarcoma: a propensity score-adjusted SEER analysis. AB - BACKGROUND: Currently no prospective randomized trial has measured the efficacy of radiation therapy for resected retroperitoneal sarcomas (RPS). Our objective was to determine the effect of radiation therapy on disease-specific and overall survival between propensity score-matched surgically resected RPS patients using the Surveillance, Epidemiology, and End Results (SEER) database. PATIENTS AND METHODS: The study population consisted of patients with histologically confirmed RPS who underwent surgical resection between 1988 and 2006. Exclusion criteria included multiple malignancies, distant metastasis, and unknown grade or stage. Cox modeling was used to determine covariate associations with disease-specific survival. Propensity score methods were used to perform survival analysis in patients who received radiation matched with patients who underwent surgery alone. RESULTS: Prior to matching, there were 762 patients (558 surgery only, 204 surgery with radiation). Factors independently associated with radiation therapy were age (P = 0.037), geographic region (P = 0.041), grade (P = 0.047), stage (P = 0.003), and surgery type (P = 0.01). Cox modeling demonstrated that age, sex, grade, and stage were independently associated with survival. Propensity scoring (309 matched pairs) and survival analysis using Kaplan-Meier methods demonstrated no difference between propensity score-matched patients receiving radiation therapy and those who did not (P = 0.35). CONCLUSION: At present, SEER patients with surgically resected RPS who received radiation therapy did not demonstrate survival benefit. PMID- 22323438 TI - Two-component in situ forming supramolecular hydrogels as advanced biomaterials in vitreous body surgery. AB - Polymeric beta-CD and poly{(2-acrylamido-2-methyl-1-propanesulfonic acid sodium salt)-co-[6-(acrylamido)-N-adamantylhexaneamide]} are synthesized to build in situ forming hydrogels based on host/guest interactions, so called physical hydrogels. The use of these hydrogels as a potential vitreous body substitute is discussed and recommended. Potential changes in cell morphology and cell vitality of the retinal ganglion cell line RGC-5 are determined. DSC experiments with artificial membrane structures are performed. The analyses show that beta-CD overrides the harmful effects of the highly toxic adamantyl-modified polymer. Although the final hydrogel is considered to be biocompatible, the application as a biomaterial has to be reconsidered. PMID- 22323439 TI - The importance of patient participation in measuring rheumatoid arthritis flares. PMID- 22323440 TI - Novel genetic association of the VTCN1 region with rheumatoid arthritis. AB - OBJECTIVE: Based upon findings in juvenile idiopathic arthritis, the genetic contribution of the VTCN1 region to rheumatoid arthritis (RA) susceptibility and anticitrullinated protein antibody (ACPA) status was investigated. VTCN1 is known to play a pivotal role in regulation of the immune system and, in soluble form, has previously been associated with higher disease activity. METHODS: Ten VTCN1 polymorphisms were genotyped in 1237 Dutch patients with RA and 1055 healthy controls. Significant findings were replicated in two independent RA populations of northern European descent consisting of 2826 patients and 2122 healthy controls. Allele distribution was analysed using a chi(2) test and combined analysis of all studies was performed using the Mantel-Haenszel fixed effects method. RESULTS: A significant association with two polymorphisms was observed in the Dutch RA population. Replication of these findings showed an overall significant association with rs4376721 and rs10923217 (OR 1.13, 95% CI 1.03 to 1.24, p=0.013 and OR 0.78, 95% CI 0.67 to 0.91, p=0.0011, respectively). Stratification for ACPA status revealed an association in the ACPA-negative subset for rs4376721 (OR 1.19, 95% CI 1.05 to 1.35, p=0.0071), while no overall significance could be observed in the ACPA-positive population. rs10923217 was associated with both subsets of the disease. CONCLUSION: These results indicate a novel genetic association with the VTCN1 region in RA susceptibility. PMID- 22323441 TI - Long-term respiratory outcome of babies born prematurely. AB - Chronic respiratory morbidity is a common adverse outcome of premature birth, particularly in infants who develop bronchopulmonary dysplasia (BPD). Prematurely born infants who had BPD may require supplementary oxygen at home for many months, but few remain oxygen dependent beyond 2 years of age. Readmission to hospital is common, particularly for those who had BPD, but only in the first 2 years after birth. The readmissions are usually for respiratory problems, particularly respiratory syncytial virus lower respiratory infections. Recurrent respiratory symptoms requiring treatment are common, particularly in those who had BPD, even at school age and in adolescence. Affected children have evidence of airways obstruction. Pulmonary function does improve with age, but children with BPD may have ongoing airflow limitation. Computed tomography of the chest gives helpful information at follow up of patients with ongoing respiratory problems who had BPD. PMID- 22323442 TI - Clinical and pharmacoeconomic aspects of omalizumab: a 4-year follow-up. AB - OBJECTIVES: The aim of this study was to assess the stability of the effectiveness of omalizumab as add-on treatment in 11 patients with severe persistent allergic asthma followed for 4 years. Secondary outcomes were safety and economic impact, in terms of use of healthcare resources. METHODS: This retrospective study was designed to analyse a series of patients with severe allergic asthma treated with omalizumab. Patients were initially enrolled as part of the CIGE025A2425 international multicentre clinical trial. At the end (week 32), 11 responsive patients went on to complete the study and continued omalizumab treatment until June 2010. The monitoring visits coincided with the timescales planned for administering the drug and for the follow up. To estimate the economic impact, the PRE-POST treatment comparison was obtained by comparing the annual pretreatment costs with an annual average of the 4-year posttreatment period costs RESULTS: After 4 years, 81.8% of patients showed a good/excellent Global Evaluation of Treatment Effectiveness scale score and 81.2% showed an excellent increase (>1.5) in the Asthma Quality of Life Questionnaire score. The average forced expiratory volume in one second (FEV(1)) at 4 years was 75.3% compared with the predicted normal value for each patient, with a net increase (p = 0.009) compared with baseline FEV(1) values (58.6%). The frequency of serious exacerbations dropped by 94.7% compared with the pretreatment period, while mild moderate exacerbations fell by 41.8%. A reduction in costs was observed for hospital admissions (97.3%), visits to emergency department (ED) (97.5%) and mild moderate exacerbations (84%). The average cost reduction of concomitant drugs remained at 36%. CONCLUSIONS: This study confirms the effectiveness and reliability of omalizumab over the long term, while providing an excellent safety profile. The additional cost due the use of omalizumab was offset by the medium- and long-term savings associated with the reduction in hospital admissions and access to ED. PMID- 22323443 TI - Diverging fates of cells of origin in acute and chronic leukaemia. AB - The large difference in phenotypes among tumour populations may stem from the stochastic origin of tumours from distinct cells - tumour cells are assumed to retain the phenotypes of the cells from which they derive. Yet, functional studies addressing the cellular origin of leukaemia are lacking. Here we show that the cells of origin of both, BCR/ABL-induced chronic myeloid (CML) and B cell acute lymphoid leukaemia (B-ALL), resemble long-term haematopoietic stem cells (LT-HSCs). During disease-maintenance, CML LT-HSCs persist to function as cancer stem cells (CSCs) that maintain leukaemia and require signalling by the transcription factor STAT5. In contrast, B-ALL LT-HSCs differentiate into CSCs that correspond to pro-B cells. This transition step requires a transient IL-7 signal and is lost in IL-7Ralpha-deficient cells. Thus, in BCR/ABLp185(+) B-ALL and BCR/ABLp210(+) CML, the final phenotype of the tumour as well as the abundance of CSCs is dictated by diverging differentiation fates of their common cells of origin. PMID- 22323444 TI - A new view to intracellular pathogens and host responses in the South of Spain. AB - A workshop on 'The Biology of Intracellular Bacterial Pathogens' was held last October in a venue of the International University of Andalusia (UNIA) located in the World Historic Heritage town of Baeza, in the South of Spain. This Workshop gathered leading scientists from around the world to discuss their latest findings related to the mechanisms that intracellular pathogens use to subvert and manipulate host cell functions. The workshop focused on novel aspects that imprint current research in this discipline, including the heterogeneous behaviour of the pathogen at the population level, the host determinants that modulate susceptibility to the infection, the search for new drugs to combat these particular types of infections and also cutting edge technologies based on new imaging approaches and the use of microfluidics. Discussion on these topics provided new insights into the biology of these pathogens and enriched the field with new ideas for understanding why colonization of the intracellular niche of eukaryotic cells is a preferred strategy used by important human pathogens. PMID- 22323445 TI - Exploiting pleiotropic activities of semaphorins as multi-target therapies for cancer. PMID- 22323446 TI - F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation to inhibit leukemic cell proliferation. AB - Hematologic maligancies exhibit a growth advantage by up-regulation of components within the molecular apparatus involved in cell-cycle progression. The SCF (Skip Cullin1-F-box protein) E3 ligase family provides homeostatic feedback control of cell division by mediating ubiquitination and degradation of cell-cycle proteins. By screening several previously undescribed E3 ligase components, we describe the behavior of a relatively new SCF subunit, termed FBXL2, that ubiquitinates and destabilizes cyclin D2 protein leading to G(0) phase arrest and apoptosis in leukemic and B-lymphoblastoid cell lines. FBXL2 expression was strongly suppressed, and yet cyclin D2 protein levels were robustly expressed in acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) patient samples. Depletion of endogenous FBXL2 stabilized cyclin D2 levels, whereas ectopically expressed FBXL2 decreased cyclin D2 lifespan. FBXL2 did not bind a phosphodegron within its substrate, which is typical of other F-box proteins, but uniquely targeted a calmodulin-binding signature within cyclin D2 to facilitate its polyubiquitination. Calmodulin competes with the F-box protein for access to this motif where it bound and protected cyclin D2 from FBXL2. Calmodulin reversed FBXL2-induced G(0) phase arrest and attenuated FBXL2-induced apoptosis of lymphoblastoid cells. These results suggest an antiproliferative effect of SCF(FBXL2) in lymphoproliferative malignancies. PMID- 22323447 TI - The mitochondrial ATP-dependent Lon protease: a novel target in lymphoma death mediated by the synthetic triterpenoid CDDO and its derivatives. AB - Synthetic triterpenoids are multitarget compounds exhibiting promise as preventative and therapeutic agents for cancer. Their proposed mechanism of action is by forming Michael adducts with reactive nucleophilic groups on target proteins. Our previous work demonstrates that the 2-cyano-3,12-dioxooleana-1,9 dien-28-oic acid (CDDO) and its derivatives promote B-lymphoid cell apoptosis through a mitochondria-mediated pathway linked to mitochondrial protein aggregation. As one function of the Lon protease is to eliminate abnormal mitochondrial proteins, we hypothesized that CDDO-induced protein aggregation and lymphoma apoptosis occur by inactivating this enzyme. Here, we show that CDDO and its derivatives directly and selectively inhibit Lon. CDDO blocks Lon-mediated proteolysis in biochemical and cellular assays, but does not inhibit the 20S proteasome. Furthermore, a biotinylated-CDDO conjugate modifies mitochondrial Lon. A striking common phenotype of CDDO-treated lymphoma cells and Lon-knockdown cells is the accumulation of electron-dense aggregates within mitochondria. We also show that Lon protein levels are substantially elevated in malignant lymphoma cells, compared with resting or activated B cells. Finally, we demonstrate that Lon knockdown leads to lymphoma cell death. Together, these findings suggest that Lon inhibition plays a contributory role in CDDO-induced lymphoma cell death, and support the concept that mitochondrial Lon is a novel anticancer drug target. PMID- 22323448 TI - Cancer/testis antigens are novel targets of immunotherapy for adult T-cell leukemia/lymphoma. AB - Adult T-cell leukemia/lymphoma (ATLL) is an intractable hematologic malignancy caused by human T-lymphotropic virus type 1 (HTLV-1), which infects approximately 20 million people worldwide. Here, we have explored the possible expression of cancer/testis (CT) antigens by ATLL cells, as CT antigens are widely recognized as ideal targets of cancer immunotherapy against solid tumors. A high percentage (87.7%) of ATLL cases (n = 57) expressed CT antigens at the mRNA level: NY-ESO-1 (61.4%), MAGE-A3 (31.6%), and MAGE-A4 (61.4%). CT antigen expression was confirmed by immunohistochemistry. This contrasts with other types of lymphoma or leukemia, which scarcely express these CT antigens. Humoral immune responses, particularly against NY-ESO-1, were detected in 11.6% (5 of 43) and NY-ESO-1 specific CD8(+) T-cell responses were observed in 55.6% (5 of 9) of ATLL patients. NY-ESO-1-specific CD8(+) T cells recognized autologous ATLL cells and produced effector cytokines. Thus, ATLL cells characteristically express CT antigens and therefore vaccination with CT antigens can be an effective immunotherapy of ATLL. PMID- 22323449 TI - Leukotriene C4 induces migration of human monocyte-derived dendritic cells without loss of immunostimulatory function. AB - Generation of human monocyte-derived dendritic cells (DCs) for cancer vaccination involves ex vivo maturation in the presence of proinflammatory cytokines and prostaglandin E(2) (PGE(2)). Although the inclusion of PGE(2) during maturation is imperative for the induction of DC migration, PGE(2) has unfavorable effects on the immunostimulatory capacity of these cells. Like PGE(2), leukotrienes (LTs) are potent mediators of DC migration. We therefore sought to characterize the migratory and immunologic properties of DCs that matured in the presence of LTB(4), LTC(4), LTD(4), and PGE(2). Here, we demonstrate that DCs matured in the presence of LTC(4), but not LTB(4) or LTD(4), are superior to PGE(2)-matured DCs in stimulating CD4(+) T-cell responses and in inducing antigen-specific cytotoxic T lymphocytes (CTLs) in vitro without concomitant induction or recruitment of regulatory T cells (Tregs). LTC(4)-matured DCs migrate efficiently through layers of extracellular matrix and secrete higher levels of immunostimulatory IL-12p70 while producing reduced levels of immune-inhibitory IL-10, IL12p40, indoleamine 2,3-dioxidase, and TIMP-1 (tissue inhibitor of matrix metalloproteinases). Intracellular calcium mobilization and receptor antagonist studies reveal that, in contrast to LTD(4), LTC(4) did not signal through CysLTR(1) in DCs. Collectively, our data suggest that LTC(4) represents a promising candidate to replace PGE(2) in DC maturation protocols for cancer vaccination. PMID- 22323450 TI - Regulation of dendritic cell development by GM-CSF: molecular control and implications for immune homeostasis and therapy. AB - Dendritic cells (DCs) represent a small and heterogeneous fraction of the hematopoietic system, specialized in antigen capture, processing, and presentation. The different DC subsets act as sentinels throughout the body and perform a key role in the induction of immunogenic as well as tolerogenic immune responses. Because of their limited lifespan, continuous replenishment of DC is required. Whereas the importance of GM-CSF in regulating DC homeostasis has long been underestimated, this cytokine is currently considered a critical factor for DC development under both steady-state and inflammatory conditions. Regulation of cellular actions by GM-CSF depends on the activation of intracellular signaling modules, including JAK/STAT, MAPK, PI3K, and canonical NF-kappaB. By directing the activity of transcription factors and other cellular effector proteins, these pathways influence differentiation, survival and/or proliferation of uncommitted hematopoietic progenitors, and DC subset-specific precursors, thereby contributing to specific aspects of DC subset development. The specific intracellular events resulting from GM-CSF-induced signaling provide a molecular explanation for GM-CSF-dependent subset distribution as well as clues to the specific characteristics and functions of GM-CSF-differentiated DCs compared with DCs generated by fms-related tyrosine kinase 3 ligand. This knowledge can be used to identify therapeutic targets to improve GM-CSF-dependent DC-based strategies to regulate immunity. PMID- 22323451 TI - Human telomere disease due to disruption of the CCAAT box of the TERC promoter. AB - Mutations in the coding region of telomerase complex genes can result in accelerated telomere attrition and human disease. Manifestations of telomere disease include the bone marrow failure syndromes dyskeratosis congenita and aplastic anemia, acute myeloid leukemia, liver cirrhosis, and pulmonary fibrosis. Here, we describe a mutation in the CCAAT box (GCAAT) of the TERC gene promoter in a family in which multiple members had typical features of telomeropathy. The genetic alteration in this critical regulatory sequence resulted in reduced reporter gene activity and absent binding of transcription factor NF-Y, likely responsible for reduced TERC levels, decreased telomerase activity, and short telomeres. This is the first description of a pathogenic mutation in the highly conserved CCAAT box and the first instance of a mutation in the promoter region of TERC producing a telomeropathy. We propose that current mutation-screening strategies should include gene promoter regions for the diagnosis of telomere diseases. This clinical trial was registered at www.clinicaltrials.gov as #NCT00071045. PMID- 22323452 TI - Knock-in of a FLT3/ITD mutation cooperates with a NUP98-HOXD13 fusion to generate acute myeloid leukemia in a mouse model. AB - Constitutive activation of FLT3 by internal tandem duplication (ITD) is one of the most common molecular alterations in acute myeloid leukemia (AML). FLT3/ITD mutations have also been observed in myelodysplastic syndrome patients both before and during progression to AML. Previous work has shown that insertion of an FLT3/ITD mutation into the murine Flt3 gene induces a myeloproliferative neoplasm, but not progression to acute leukemia, suggesting that additional cooperating events are required. We therefore combined the FLT3/ITD mutation with a model of myelodysplastic syndrome involving transgenic expression of the Nup98 HoxD13 (NHD13) fusion gene. Mice expressing both the FLT3/ITD and NHD13 transgene developed AML with 100% penetrance and short latency. These leukemias were driven by mutant FLT3 expression and were susceptible to treatment with FLT3 tyrosine kinase inhibitors. We also observed a spontaneous loss of the wild-type Flt3 allele in these AMLs, further modeling the loss of the heterozygosity phenomenon that is seen in human AML with FLT3-activating mutations. Because resistance to FLT3 inhibitors remains an important clinical issue, this model may help identify new molecular targets in collaborative signaling pathways. PMID- 22323453 TI - Tim-3 is an inducible human natural killer cell receptor that enhances interferon gamma production in response to galectin-9. AB - NK-cell function is regulated by the integration of signals received from activating and inhibitory receptors. Here we show that a novel immune receptor, T cell Ig and mucin-containing domain-3 (Tim-3), is expressed on resting human NK cells and is up-regulated on activation. The NK92 NK-cell line engineered to overexpress Tim-3 showed a marked increase in IFN-gamma production in the presence of soluble rhGal-9 or Raji tumor cells engineered to express Gal-9. The Tim-3(+) population of low-dose IL-12/IL-18-activated primary NK cells significantly increased IFN-gamma production in response to soluble rhGal-9, Gal 9 presented by cell lines, and primary acute myelogenous leukemia (AML) targets that endogenously express Gal-9. This effect is highly specific as Tim-3 Ab blockade significantly decreased IFN-gamma production, and Tim-3 cross-linking induced ERK activation and degradation of IkappaBalpha. Exposure to Gal-9 expressing target cells had little effect on CD107a degranulation. Reconstituted NK cells obtained from patients after hematopoietic cell transplantation had diminished expression of Tim-3 compared with paired donors. This observation correlates with the known IFN-gamma defect seen early posttransplantation. In conclusion, we show that Tim-3 functions as a human NK-cell coreceptor to enhance IFN-gamma production, which has important implications for control of infectious disease and cancer. PMID- 22323454 TI - Elevated serum IL-10 levels in diffuse large B-cell lymphoma: a mechanism of aberrant JAK2 activation. AB - Cytokines are deregulated in cancers and can contribute to tumor growth. In patients with diffuse large-cell lymphoma (DLBCL), we observed higher levels of JAK/STAT pathway-related serum cytokines (ie, IL-6, IL-10, epidermal growth factor, and IL-2) compared with controls. Of these, only IL-10 activated the JAK2 pathway in lymphoma cells in vitro. Patients with high serum IL-10 had shorter event-free survival (EFS) than patients with low levels (P > .01) and high IL-10 was correlated with high lactase dehydrogenase (P = .0085) and higher International Prognostic Index scores (P = .01). To explore the mechanism by which IL-10 may contribute to an inferior EFS, we investigated the effect of IL 10 on the JAK2 pathway and found that the IL-10/IL-10 receptor complex up regulated JAK2 signaling. Neutralizing Ab to IL-10 inhibited constitutive and IL 10-induced JAK2/STAT3 phosphorylation. JAK2 inhibition dephosphorylated JAK2 and STAT3 and caused an inhibitory effect on phospho-JAK2-positive DLBCL cells; there was a minimal effect on phospho-JAK2-negative cells. Apoptosis induced by JAK2 inhibition was dependent on inhibition of autocrine IL-10 and c-myc expression and independent of Bcl-2 family expression. These results provide the rationale for testing JAK2 inhibitors in DLBCL patients, and indicate that serum IL-10 may be a biomarker to identify patients more likely to respond to JAK2-targeted therapy. PMID- 22323455 TI - Gateway-compatible transposon vector to genetically modify human embryonic kidney and adipose-derived stromal cells. AB - The Gateway technology cloning system and transposon technology represent state of-the-art laboratory techniques. Combination of these molecular tools allows rapid cloning of target genes into expression vectors. Here, we describe a novel Gateway technology-compatible transposon plasmid that combines the advantages of Gateway recombination cloning with the Sleeping Beauty (SB) transposon-mediated transgene integrations. In our system the transposition is catalyzed by the novel hyperactive SB100x transposase, and provides highly efficient and precise transgene integrations into the host genome. A Gateway-compatible transposon plasmid was generated in which the potential target gene can be fused with a yellow fluorescent protein (YFP) tag at the N-terminal. The vector utilizes the CAGGS promoter to control fusion protein expression. The transposon expression vector encoding the YFP-interferon-beta protein (IFNB1) fusion protein together with the hyperactive SB100x transposase was used to generate stable cell lines in human embryonic kidney (HEK293) and rat adipose-derived stromal cells (ASC). ASCs and HEK293 cells stably expressed and secreted the human IFNB1 for up to 4 weeks after transfection. The generated Gateway-compatible transposon plasmid can be utilized for numerous experimental approaches, such as gene therapy or high throughput screening methods in primary cells, representing a valuable molecular tool for laboratory applications. PMID- 22323456 TI - Identification of RALDH2 as a visually regulated retinoic acid synthesizing enzyme in the chick choroid. AB - PURPOSE: All-trans-retinoic acid (atRA) has been implicated in the local regulation of scleral proteoglycan synthesis in vivo. The purpose of the present study was to identify the enzymes involved in the synthesis of atRA during visually guided ocular growth, the cells involved in modulation of atRA biosynthesis in the choroid, and the effect of choroid-derived atRA on scleral proteoglycan synthesis. METHODS: Myopia was induced in White leghorn chicks by form deprivation for 10 days, followed by up to 15 days of unrestricted vision (recovery). Expression of atRA synthesizing enzymes was evaluated by semiquantitative qRT-PCR, in situ hybridization, and immunohistochemistry. atRA synthesis was measured in organ cultures of isolated choroids using LC-tandem MS quantification. Scleral proteoglycan synthesis was measured in vitro by the incorporation of (35)SO(4) in CPC-precipitable glycosaminoglycans. RESULTS; RALDH2 was the predominant RALDH transcript in the choroid (> 100-fold that of RALDH3). RALDH2 mRNA was elevated after 12 and 24 hours of recovery (60% and 188%, respectively; P < 0.01). The atRA concentration was significantly higher in cultures of choroids from 24-hour to 15-day recovering eyes than in paired controls (-195%; P < 0.01). Choroid conditioned medium from recovering choroids inhibited proteoglycan synthesis to 43% of controls (P < 0.02, paired t-test; n = 16) and produced a relative inhibition corresponding to a RA concentration of 7.20 * 10(-8) M. CONCLUSIONS: The results of this study suggest that RALDH2 is the major retinal dehydrogenase in the chick choroid and is responsible for increased atRA synthesis in response to myopic defocus. PMID- 22323457 TI - iSyTE: integrated Systems Tool for Eye gene discovery. AB - PURPOSE: To facilitate the identification of genes associated with cataract and other ocular defects, the authors developed and validated a computational tool termed iSyTE (integrated Systems Tool for Eye gene discovery; http://bioinformatics.udel.edu/Research/iSyTE). iSyTE uses a mouse embryonic lens gene expression data set as a bioinformatics filter to select candidate genes from human or mouse genomic regions implicated in disease and to prioritize them for further mutational and functional analyses. METHODS: Microarray gene expression profiles were obtained for microdissected embryonic mouse lens at three key developmental time points in the transition from the embryonic day (E)10.5 stage of lens placode invagination to E12.5 lens primary fiber cell differentiation. Differentially regulated genes were identified by in silico comparison of lens gene expression profiles with those of whole embryo body (WB) lacking ocular tissue. RESULTS: Gene set analysis demonstrated that this strategy effectively removes highly expressed but nonspecific housekeeping genes from lens tissue expression profiles, allowing identification of less highly expressed lens disease-associated genes. Among 24 previously mapped human genomic intervals containing genes associated with isolated congenital cataract, the mutant gene is ranked within the top two iSyTE-selected candidates in approximately 88% of cases. Finally, in situ hybridization confirmed lens expression of several novel iSyTE-identified genes. CONCLUSIONS: iSyTE is a publicly available Web resource that can be used to prioritize candidate genes within mapped genomic intervals associated with congenital cataract for further investigation. Extension of this approach to other ocular tissue components will facilitate eye disease gene discovery. PMID- 22323458 TI - RpgrORF15 connects to the usher protein network through direct interactions with multiple whirlin isoforms. AB - PURPOSE: Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene are a frequent cause of X-linked retinitis pigmentosa. The RPGR transcript undergoes complex alternative splicing to express both constitutive (Rpgr(ex1-19)) and Rpgr(ORF15) variants. Because functional studies of Rpgr suggest a role in intracellular protein trafficking through the connecting cilia, the goal of this study was to identify potential binding partners for Rpgr(ORF15) and to identify the domains on whirlin necessary for Rpgr binding. METHODS: The C-terminus of mouse Rpgr(ORF15) was used as bait in a yeast two-hybrid system. Whirlin expression was analyzed using RT-PCR and Western blot analysis. Protein-protein interactions were confirmed using in vitro binding assays and coimmunoprecipitation. Subcellular colocalization was analyzed using immunohistochemistry on retinal cryosections. RESULTS: Yeast two-hybrid analysis identified whirlin, a PDZ-scaffold protein, as a putative binding partner for Rpgr(ORF15). The RPGR(ORF15)-whirlin interaction was confirmed using in vitro binding assays and coimmunoprecipitation from retinal tissue, and both proteins were shown to colocalize in the photoreceptor connecting cilia in vivo. Results from RT-PCR, Western blot analysis, and immunocytochemistry demonstrated that whirlin expressed multiple isoforms in photoreceptors with variable subcellular localization. CONCLUSIONS: Whirlin expression has been reported in photoreceptors and cochlear hair cells, and mutations in whirlin cause Usher syndrome (USH2D) and nonsyndromic congenital deafness (DFNB31). Because mutations in the 5' end of whirlin are associated with the syndromic phenotype associated with USH2D, the identification of novel N-terminal isoforms in the retina and a novel RPGR(ORF15) whirlin interaction provide a potential mechanism for the retinal phenotype observed in USH2D. PMID- 22323459 TI - Human aqueous humor phosphatase activity in cataract and glaucoma. AB - PURPOSE: To investigate the presence and activity of protein phosphatase-2A (PPase2A), protein phosphatase-2C (PPase2C), and protein tyrosine phosphatases (PTPs) in the human aqueous humor (AH) of patients with primary open-angle glaucoma (POAG) and cataract and to study the correlation between these phosphatases and the redox state of the AH. METHODS: Eighty-six cataract patients and 29 POAG patients who were scheduled for cataract surgery with or without glaucoma surgery were enrolled in the study. PPase2A, PPase2C, and PTPs levels in AH were measured by enzyme-linked immunosorbent assays, Western blot analyses, and spectral METHODS: The redox state was measured by spectral and fluorescent methods. RESULTS: Phosphatase activity-positive results were significantly higher in AH samples from the POAG group (PP2A chi(2)(1) = 11.754, P < 0.01; PP2C chi(2)(1) = 8.754, P < 0.01; PTP chi(2)(1) = 11.073, P < 0.01). Western blot analysis revealed higher PP2C levels in the AH of glaucoma patients compared with PP2C levels in the AH of cataract patients (P = 0.012). Both oxidized/reduced glutathione ratios and superoxide dismutase levels in the AH were significantly higher in the glaucoma group than in the cataract group. Finally significant correlations were found between PP2A and PP2C, PP2A and PTP, and total antioxidant activity and PTP levels. CONCLUSIONS: There is a statistically significant difference between phosphatase levels in the AH of POAG patients and cataract patients. The phosphatase content of the AH represents tissue pathology, but their presence in the AH may be attributed to cell debris or to active signaling to other molecular events. PMID- 22323460 TI - Mitomycin C retardation of corneal fibroblast migration via sustained dephosphorylation of paxillin at tyrosine 118. AB - PURPOSE: To investigate how mitomycin C (MMC) modulates corneal fibroblast migration and its molecular mechanisms in the wound healing process. METHODS: After treatment with 0 and 0.2 mg . mL(-1) MMC for 5 minutes, effect of MMC on cell migration of human corneal fibroblasts (HCFs) was examined with a cell migration assay. Both focal adhesion kinase (FAK) and paxillin (PXN) expressions in HCFs were analyzed by semiquantitative real-time PCR, immunoblotting, and immunofluorescence confocal microscopy. Using gene silencing or gene overexpression with lentiviral-based pseudovirion infection, the phosphorylation level of FAK, PXN, and mutated PXNs at tyrosine sites 31 (Y31F-EGFP) and 118 (Y118F-EGFP) were verified in HCFs. RESULTS: MMC retarded HCF migration at 1 and 2 days posttreatment (dpt). MMC reduced levels of FAK transcript and FAK protein, but increased both transcript and protein expression of PXN at 1 and 2 dpt. Furthermore, MMC upregulated FAK-pY397, which subsequently enhanced PXN-pY31 in a dose-dependent manner at 1 dpt. Concurrently, MMC downregulated PXN-pY118 at 1 dpt. However, MMC treatment resulted in dephosphorylation of FAK-pY397, PXN-pY31, and PXN-pY118 at 2 dpt. The FAK/PXN complex in MMC-treated HCFs was detected at focal adhesion sites more than at the leading edge at 1 and 2 dpt, contributing to retardation of HCF migration. Y118F-EGFP-expressing HCFs exhibited lower mobility than that of PXN-EGFP- or Y31F-EGFP-expressing HCFs. CONCLUSIONS: The sustained PXN-pY118 dephosphorylation resulted in steadfastness of an incompletely active FAK/PXN complex at focal adhesion sites and played a pivotal role in MMC-retarded HCF migration. PMID- 22323461 TI - An allele of microtubule-associated protein 1A (Mtap1a) reduces photoreceptor degeneration in Tulp1 and Tub Mutant Mice. AB - PURPOSE: To identify genes that modify photoreceptor cell loss in the retinas of homozygous Tulp1(tm1Pjn) and Tub(tub) mice, which exhibit juvenile retinitis pigmentosa. METHODS: Modifier loci were identified by genetic quantitative trait locus analysis. F2 Tulp1(tm1Pjn/tm1Pjn) mutant mice from a B6 Tulp1(tm1Pjn/tm1Pjn) * AKR/J intercross were genotyped with a panel of single nucleotide polymorphism markers and phenotyped by histology for photoreceptor nuclei remaining at 9 weeks of age. Genotype and phenotype data were correlated and examined with Pseudomarker 2.02 using 128 imputations to map modifier loci. Thresholds for the 63%, 10%, 5%, and 1% significance levels were obtained from 100 permutations. A significant, protective candidate modifier was identified by bioinformatic analysis and confirmed by crossing transgenic mice bearing a protective allele of this gene with Tulp1- and Tub-deficient mice. RESULTS: A significant, protective modifier locus on chromosome 2 and a suggestive locus on chromosome 13 that increases photoreceptor loss were identified in a B6 Tulp1(tm1Pjn/tm1Pjn) * AKR/J intercross. The chromosome 2 locus mapped near Mtap1a, which encodes a protein associated with microtubule-based intracellular transport and synapse function. The protective Mtap1a(129P2/OlaHsd) allele was shown to reduce photoreceptor loss in both Tulp1(tm1Pjn/tm1Pjn) and Tub(tub/tub) mice. CONCLUSIONS: It was demonstrated that the gene Mtap1a, which modifies hearing loss in Tub(tub/tub) mice, also modifies retinal degeneration in Tub(tub/tub) and Tulp1(tm1Pjn/tm1Pjn) mice. These results suggest that functionally nonredundant members of the TULP family (TUB and TULP1) share a common functional interaction with MTAP1A. PMID- 22323462 TI - Correlation of tear inflammatory cytokines and matrix metalloproteinases with four dry eye diagnostic tests. AB - PURPOSE: Tear cytokines and matrix metalloproteinases (MMPs) can be extracted from the Schirmer strip. This study examined the extracted levels of tear cytokines and MMPs from Schirmer strips and potential correlation with Schirmer's test, tear breakup time (TBUT), tear osmolarity, and ocular surface disease index (OSDI). METHODS: Thirty healthy volunteers were clinically evaluated for known methods to diagnose dry eye disease, including Schirmer's test, tear osmolarity, OSDI, and TBUT. Tears were collected by Schirmer strips and proteins were extracted from the Schirmer strip in 0.5 M NaCl with 0.5% Tween 20 and analyzed using multiplex assay kits to examine cytokines or MMPs. Calculated cytokine and MMP concentrations for all samples were sorted into groups according to a positive or negative for each of the above-cited four dry eye diagnostic tests, individually and in combination. RESULTS: Five inflammatory cytokines (IL-1alpha, -1beta, -6, -8, and TNF-alpha) and five MMPs (MMPs 1, 2, 7, 9, and 10) were extracted from clinical Schirmer strips. Schirmer strip measurement and tear osmolarity correlated well with increased concentrations of the inflammatory cytokines and MMPs, whereas TBUT and OSDI did not. CONCLUSIONS: Both the Schirmer's test and tear osmolarity may be more relevant to the clinician in the diagnosis of ocular surface diseases with an increased level of inflammatory mediators. PMID- 22323463 TI - Optical coherence tomographic reflectivity of photoreceptors beneath cystoid spaces in diabetic macular edema. AB - PURPOSE: To investigate the relationship between the cystoid spaces in the outer plexiform layer (OPL) and the characteristics of the photoreceptors beneath the cystoid spaces in patients with diabetic macular edema (DME). METHODS: In this observational cross-sectional study, 123 eyes of 96 consecutive patients with clinically significant macular edema were retrospectively reviewed. The characteristics of the photoreceptors on optical coherence tomography (OCT) images represented by the external limiting membrane (ELM) and the junction between inner and outer segments (IS/OS), and their association with the overlying cystoid spaces were investigated. RESULTS: The areas beneath the cystoid spaces in the OPL had a longer transverse length of disrupted or faint IS/OS and disrupted ELM lines than those without cystoid spaces (P < 0.001, P < 0.001, and P = 0.009). The IS/OS lines beneath the cystoid spaces had higher reflectivity than those in areas without cystoid spaces (P < 0.001). Enlarged cystoid spaces extending from the inner nuclear layer to the OPL were associated with disrupted IS/OS or ELM but not faint IS/OS (P < 0.001, P < 0.001, and P = 0.467). The transverse length of disrupted IS/OS at the fovea was correlated with the logarithm of the minimum angle of resolution (logMAR) more than the association between foveal thickness and logMAR (r = 0.49, P < 0.001 vs. r = 0.28, P = 0.002). The ELM descended to the RPE more frequently in eyes with single-lobulated fluorescein pooling in the foveal avascular zone than those with multi-lobulated pooling (P < 0.001). CONCLUSIONS: OCT showed that the cystoid spaces in the OPL were accompanied by photoreceptor damage beneath the cystoid spaces in DME. PMID- 22323464 TI - Femtosecond lenticule extraction (FLEx): clinical results, interface evaluation, and intraocular pressure variation. AB - PURPOSE: To characterize the clinical profile of femtosecond lenticule extraction (FLEx) correlated with ultrastructural analysis of the corneal interface and in vivo real-time intraocular pressure (IOP). METHODS: Prospective clinical case series with experimental studies; consecutive patients underwent FLEx at a single tertiary center over 10 months with postsurgical follow-up of 3 months. The patients were divided into three groups according to spherical equivalence (SE) (A, < -5.0 diopters [D]; B, >= -5.00 D and < -9.00 D; and C, >= -9.0 D). Twelve human cadaveric eyes analyzed using scanning electron microscopy after receiving FLEx; 40 rabbit eyes received FLEx with in vivo IOP measurements. The main outcome measures were refractive outcomes from study subjects; with corneal interface and IOP in experimental studies. RESULTS: Thirty-three subjects (22 females, 66.7%) underwent FLEx in both eyes (66 eyes). Mean age was 32 years (range, 21 to 46 years). Preoperative mean SE was -5.77 +/- 2.04 D with astigmatism of -1.03 +/- 0.72 D. There was a slight hyperopic shift (mean SE 0.14 +/- 0.53 D); 94% achieved uncorrected visual acuity >=20/25 3 months postoperatively. Refractive stability was achieved within 1 month (P < 0.001). Ultrastructurally, the smoothness of the corneal interface was independent of ablation depth (mean irregularity scores A, B, C: 8.8 +/- 0.6, 10.3 +/- 0.4, 8.7 +/- 0.6, respectively; P = 0.88). The increase in IOP during FLEx was similar to that in femtosecond (FS)-LASIK, albeit a twofold duration of raised IOP in FLEx (P < 0.001). CONCLUSIONS: These results suggest that FLEx is predictable and effective in treating myopia and myopic astigmatism. Experimental studies support the early clinical results and safety of this procedure. PMID- 22323465 TI - Targeting of junctional adhesion molecule-C inhibits experimental choroidal neovascularization. AB - PURPOSE: To identify the expression of junctional adhesion molecule-C (JAM-C) in choroidal neovascularization (CNV) and evaluate the effect of JAM-C targeting on CNV formation and on cellular functions relevant to CNV in vitro, such as macrophage transmigration, human retinal pigment epithelial (hRPE) cell migration, and monolayer RPE permeability. METHODS: JAM-C expression in CNV was analyzed by real-time PCR, immunoblot analysis, and immunofluorescence staining. CNV area and blood vessel leakage were quantified using isolectin B4 staining and fluorescein angiography, respectively, 1 week after laser treatment. Macrophage infiltration within the CNV area was measured by immunofluorescence, and transmigration through monolayer RPE was analyzed using a transepithelial migration assay. After JAM-C shRNA transfection, human RPE cell migration was quantified using a transwell assay, and monolayer RPE permeability was determined by measuring the apical-to-basolateral movements of sodium fluorescein. RESULTS: JAM-C expression was upregulated during CNV formation after laser treatment in a time-dependent manner. However, no change in JAM-C expression was found in the retina up to 14 days after laser treatment. JAM-C targeting by intravitreal injection of JAM-C Fc chimera inhibited CNV, blood vessel leakage, and macrophage infiltration. JAM-C Fc chimera inhibited basolateral-to-apical transmigration in vitro through a monolayer of hRPE of macrophages from patients with wet AMD. In addition, shRNA-mediated JAM-C knockdown inhibited hRPE cell migration and hRPE permeability. CONCLUSIONS: JAM-C blockade may prove useful for CNV suppression by inhibiting macrophage transmigration, RPE cell migration, and monolayer RPE barrier malfunction. PMID- 22323466 TI - Relationship between the foveal avascular zone and foveal pit morphology. AB - PURPOSE: To assess the relationship between foveal pit morphology and size of the foveal avascular zone (FAZ). METHODS: Forty-two subjects were recruited. Volumetric images of the macula were obtained using spectral domain optical coherence tomography. Images of the FAZ were obtained using either a modified fundus camera or an adaptive optics scanning light ophthalmoscope. Foveal pit metrics (depth, diameter, slope, volume, and area) were automatically extracted from retinal thickness data, whereas the FAZ was manually segmented by two observers to extract estimates of FAZ diameter and area. RESULTS: Consistent with previous reports, the authors observed significant variation in foveal pit morphology. The average foveal pit volume was 0.081 mm(3) (range, 0.022 to 0.190 mm(3)). The size of the FAZ was also highly variable between persons, with FAZ area ranging from 0.05 to 1.05 mm(2) and FAZ diameter ranging from 0.20 to 1.08 mm. FAZ area was significantly correlated with foveal pit area, depth, and volume; deeper and broader foveal pits were associated with larger FAZs. CONCLUSIONS: Although these results are consistent with predictions from existing models of foveal development, more work is needed to confirm the developmental link between the size of the FAZ and the degree of foveal pit excavation. In addition, more work is needed to understand the relationship between these and other anatomic features of the human foveal region, including peak cone density, rod-free zone diameter, and Henle fiber layer. PMID- 22323467 TI - NF-kappaB is the transcription factor for FGF-2 that causes endothelial mesenchymal transformation in cornea. AB - PURPOSE: To determine the role of nuclear factor-kappaB (NF-kappaB) during FGF-2 mediated endothelial mesenchymal transformation (EMT) in response to interleukin (IL)-1beta stimulation in corneal endothelial cells (CECs). METHODS: Expression and/or activation of IL-1 receptor-associated protein kinase (IRAK), TNF receptor associated factor 6 (TRAF6), phosphatidylinositol 3-kinase (PI 3-kinase), IkappaB kinase (IKK), IkappaB, NF-kappaB, and FGF-2 were analyzed by immunoblot analysis. Cell proliferation was measured by 3-(4,5-dimethylthiazolyl-2)-2,5 diphenyltetrazolium bromide (MTT) assay. NF-kappaB activity was measured by NF kappaB ELISA kit, while binding of NF-kappaB to the promoter region of FGF-2 gene was determined by chromatin immunoprecipitation. RESULTS: Brief stimulation of CECs with IL-1beta upregulated expression of IRAK and TRAF6 and activated PI 3 kinase; expression of IRAK and TRAF6 reached maximum within 60 minutes, after which the expression disappeared, while PI 3-kinase activity was observed up to 4 hours after IL-1beta stimulation. Use of specific inhibitor to PI 3-kinase or IRAK demonstrated that IRAK activates PI 3-kinase, the signaling of which phosphorylates IKKalpha/beta and degrades IkappaB, subsequently leading to activation of NF-kappaB. The induction of FGF-2 by IL-1beta was completely blocked by inhibitors to NF-kappaB activation (sulfasalazine) or PI 3-kinase (LY294002), and both inhibitors greatly blocked cell proliferation of CECs. Chromatin immunoprecipitation further demonstrated that NF-kappaB is the transcription factor of FGF-2 as NF-kappaB binds the putative NF-kappaB binding site of the FGF-2 promoter. CONCLUSIONS: These data suggest that IL-1beta signaling combines the canonical pathway and the PI 3-kinase signaling to upregulate FGF-2 production through NF-kappaB, which plays a key role as a transcription factor of FGF-2 gene. PMID- 22323468 TI - The diurnal variation of matrix metalloproteinase-9 and its associated factors in human tears. AB - PURPOSE: Matrix metalloproteinases (MMPs) are degrading enzymes which maintain and remodel tissue architecture. Upregulation of MMP-9 has been associated with corneal erosions and ulceration. As these conditions are often exacerbated on waking, suggesting that degrading activity is upregulated overnight, this study set out to determine the diurnal variation of MMP-9, Tissue Inhibitor of Metalloproteinase (TIMP)-1, and Neutrophil Gelatinase-Associated Lipocalin (NGAL). METHODS: Flush tears were collected from 46 healthy, non-contact lens wearers at midday, before sleep, and immediately on waking. Total protein content (TPC) was measured using the bicinchoninic acid method, and MMP-9, TIMP-1, and NGAL concentrations were measured using sandwich enzyme-linked immunoassay. Statistical analysis was performed using repeated measures analysis of variance. RESULTS: TPC was 3.4 +/- 1.5 mg/mL, 5.0 +/- 3.7 mg/mL and 15.5 +/- 8.4 mg/mL for midday, before sleep, and on waking respectively, the latter being significantly greater than the other two (P < 0.001). MMP-9 concentrations at the corresponding time points were 9.8 +/- 14.3 ng/mL, 8.5 +/- 11.7 ng/mL, and 2000.7 +/- 1950.7 ng/mL. Again, the value on waking was significantly greater than the previous two visits (P < 0.001). TIMP-1 concentrations exceeded those of MMP-9 at midday but the ratio of the two reversed on awakening. CONCLUSIONS: Concentrations of MMP-9 are negligible during the day and completely inhibited by TIMP-1. On awakening, MMP-9 increases 200-fold, an increase that is not completely inhibited by TIMP-1. This diurnal change, along with the presence of NGAL which protects MMP-9 from degradation, suggests that the closed eye is an environment conducive to extracellular matrix remodeling. PMID- 22323469 TI - Body mass index has a linear relationship with cerebrospinal fluid pressure. AB - PURPOSE: To examine the relationship between body mass index (BMI) and cerebrospinal fluid pressure (CSFP), as low BMI and low CSFP have recently been described as risk factors for primary open-angle glaucoma (POAG). METHODS: This was a retrospective review of the electronic medical records of patients who had CSFP measured by lumbar puncture and data to calculate BMI at the Mayo Clinic (Rochester, MN). Exclusion criteria included diagnoses, surgical procedures and medications known to affect CSFP. Mean CSFP for each unit BMI was calculated. The probabilities were two-tailed, and the alpha level was set at P < 0.05. Patients with documented BMI, CSFP, and intraocular pressure (IOP) were analyzed for the relationship between IOP and BMI. RESULTS: A total of 4235 patients, primarily of Caucasian descent, met the entry criteria. Median BMI was 26 and the mean CSFP was 10.9 +/- 2.6 mm Hg. The increase in CSFP with increasing BMI was linear with an r(2) = 0.20 (P < 0.001). CSFP increased by 37.7% from BMI 18 (8.6 +/- 2.1 mm Hg) to BMI 39 (14.1 +/- 2.5 mm Hg). The r(2) (0.21) of the model of BMI and sex was similar to the r(2) of a BMI-only model (0.20). There was no relation between IOP and BMI within a subgroup of the study population (r (2) = 0.005; P = 0.14). CONCLUSIONS: CSFP has a positive, linear relationship with BMI. IOP is not influenced by BMI. If CSFP influences the risk for POAG, then individuals with a lower BMI may have an increased risk for developing POAG. Similarly, a higher BMI may be protective. PMID- 22323470 TI - A novel experimental mouse model of retinal detachment: complete functional and histologic recovery of the retina. AB - PURPOSE: To establish an experimental mouse model of retinal detachment (RD) created by corneal puncture (CP). METHODS: Mouse corneas were punctured with a 30.5-gauge beveled needle, and the anterior chamber was penetrated. Histologic and functional changes of the retina were examined by light microscopy and electroretinography (ERG). Certain retinal cellular responses were examined by immunofluorescence microscopy. Internucleosomal DNA fragmentation in the retina was determined by terminal deoxynucleotidyl transferase-mediated uridine 5' triphosphate-biotin nick-end labeling (TUNEL). RESULTS. CP caused transient leakage of aqueous humor along the needle shaft and immediate formation of multiple retinal blebs, which shrank and flattened within 24 hours. Bleb formation was associated with detachment of the neuroretina from the retinal pigment epithelium (RPE). After CP, the RPE cells underwent extensive transformation during retinal detachment/reattachment, but they resumed normal morphology on retinal reattachment around 10 to 13 days after CP. Relative to pre CP ERG amplitudes, the punctured eyes showed decreases of 45% and 24% in scotopic and 7% and 12% in photopic b- and a-wave amplitudes, respectively, within 10 to 20 minutes after CP. The ERG amplitudes recovered fully by 12 hours after CP. No infiltrated cells were observed in the subretinal space, and no proliferating or TUNEL-positive cells were observed in the retina of the punctured eyes. CONCLUSIONS: Puncturing the mouse cornea can create transient RD, and the functional and histologic changes in the retina can subsequently recover. This experimental mouse model of RD mimics human traction and serous RD. PMID- 22323471 TI - Spectral-domain optical coherence tomography of beta-zone peripapillary atrophy: influence of myopia and glaucoma. AB - PURPOSE: To investigate the influence of glaucoma and myopia on the cross sectional configuration of the beta-zone of peripapillary atrophy (PPA-beta) using spectral-domain optical coherence tomography (SD-OCT). METHODS: Cross sectional B-scan images of PPA-beta obtained with SD-OCT were evaluated in 100 eyes of 100 consecutive patients with POAG, regardless of intraocular pressure level, and in 100 eyes of 100 normal subjects. PPA bed configurations were classified, and associated factors were studied with multivariate analysis. RESULTS: In 147 eyes with PPA-beta (84 POAG and 63 normal eyes; P = 0.0012), the PPA bed was composed of straight (14 POAG and 27 normal eyes) or downward-curved (19 and 8 eyes) Bruch's membrane (BM) or of a downward-bending slope lacking BM (BM defect; 51 and 28 eyes). Multivariate analysis revealed that absence of POAG (odds ratio [OR], 0.36; P = 0.034) and less myopic refractive error (OR, 1.43; P = 0.009) were significantly associated with straight-BM-type, presence of POAG (OR, 5.74; P = 0.008) and less myopic refractive error (OR, 3.02; P < 0.001) with curved-BM-type, and myopic refractive error (OR, 0.34; P < 0.001) with BM-defect type. Within the PPA-beta region, all retinal layers except for the nerve fiber layer frequently disappeared before reaching the disc edge, showing no significant intergroup difference (P > 0.05) between POAG and normal eyes. CONCLUSIONS: PPA bed configurations detected by SD-OCT were classified into three types. The lack of BM on the PPA bed was closely associated with myopia. The downward-curved appearance of BM may be related to the anatomic changes associated with glaucoma. PMID- 22323473 TI - Dietary ascorbic acid as a means to counter the stress of cypermethrin on the growth of freshwater catfish Heteropneustes fossilis. AB - Two months of experiments performed in outdoor vats in a 3 3 factorial design to evaluate the effects of three sublethal levels (0.0, 0.3 and 0.5 ug L(-1)) of cypermethrin on freshwater catfish Heteropneustes fossilis fed with three different levels (0.0, 0.5 and 1.0 g kg(-1)) of ascorbic acid (AA) in the diet. Even the lower sublethal level (0.3 ug L(-1)) of cypermethrin produced significant reduction in growth and deposition of protein in the body of H. fossilis. Dietary supplement of AA at 0.5 g kg(-1) failed to counter these ill effects of cypermethrin on H. fossilis, but a supplement of 1.0 g kg(-1) AA significantly increased the AA reserve in the body of the fish, and the ill effects of cypermethrin on growth were reversed. It was concluded that the catfish H. fossilis required an exogenous supply of AA to counter the stress of cypermethrin. PMID- 22323474 TI - Effects of maternally exposed colouring food additives on cognitive performance in rats. AB - Artificial food colourings and additives (AFCAs) have long been suggested to adversely affect the learning and behaviour in children. In this study, we aimed to provide additional data to clarify the possible side effects of colouring additives on behaviour and memory. We administered acceptable daily intake values of AFCAs as a mixture (Eritrosin, Ponceau 4R, Allura Red AC, Sunset Yellow FCF, Tartrazin, Amaranth, Brilliant Blue, Azorubin and Indigotin) to female rats before and during gestation and then tested their effects on behaviour and on spatial working memory in their offspring. Effects on spatial learning and memory were evaluated by Morris water maze, behavioural effects were evaluated by open field test and forced swim test. Our results showed that commonly used artificial food colourings have no adverse effects on spatial working memory and did not create a depressive behaviour in offspring. But they showed a few significant effects on locomotor activity as AFCAs increased some parameters of locomotor activity. PMID- 22323472 TI - Cardiovascular biology of the incretin system. AB - Glucagon-like peptide-1 (GLP-1) is an incretin hormone that enhances glucose stimulated insulin secretion and exerts direct and indirect actions on the cardiovascular system. GLP-1 and its related incretin hormone, glucose-dependent insulinotropic polypeptide, are rapidly inactivated by the enzyme dipeptidyl peptidase 4 (DPP-4), a key determinant of incretin bioactivity. Two classes of medications that enhance incretin action, GLP-1 receptor (GLP-1R) agonists and DPP-4 inhibitors, are used for the treatment of type 2 diabetes mellitus. We review herein the cardiovascular biology of GLP-1R agonists and DPP-4 inhibitors, including direct and indirect effects on cardiomyocytes, blood vessels, adipocytes, the control of blood pressure, and postprandial lipoprotein secretion. Both GLP-1R activation and DPP-4 inhibition exert multiple cardioprotective actions in preclinical models of cardiovascular dysfunction, and short-term studies in human subjects appear to demonstrate modest yet beneficial actions on cardiac function in subjects with ischemic heart disease. Incretin based agents control body weight, improve glycemic control with a low risk of hypoglycemia, decrease blood pressure, inhibit the secretion of intestinal chylomicrons, and reduce inflammation in preclinical studies. Nevertheless, there is limited information on the cardiovascular actions of these agents in patients with diabetes and established cardiovascular disease. Hence, a more complete understanding of the cardiovascular risk to benefit ratio of incretin-based therapies will require completion of long-term cardiovascular outcome studies currently underway in patients with type 2 diabetes mellitus. PMID- 22323475 TI - Citric acid production from Aspergillus niger MT-4 using hydrolysate extract of the insect Locusta migratoria. AB - Citric acid (CA) is the most important organic acid used in the food and other industries. Locusta migratoria is an insect species, which has rich nutritional composition (especially protein) and cultivated in some countries. Therefore, the present study investigated the usability of hydrolysate extract of L. migratoria biomass as substrate for the production of CA from Aspergillus niger MT-4. The insect extract (IE) was found to be rich in ash (34.9 g/100 g), protein (35.6 g/100 g) and mineral contents. Yeast extract was found to be the most favorable substrate for biomass production, whereas the maximum production of CA (41.8 g/L) was achieved in the medium containing IE. Besides, uniform pellets with the smallest size (4 mm) were observed in IE medium. It was thought that rich magnesium (6.78 g/100 g) and manganese (1.14 g/100 g) contents of IE increased the production of CA, resulting in the formation of small uniform pellets. This is the first report on the effect of protein-rich insect biomasses on the production of CA. In this regard, L. migratoria biomass was tested for the first time as a CA-production substrate. PMID- 22323476 TI - The effects of exposure to electromagnetic field on rat myocardium. AB - Exposure to electromagnetic fields (EMFs) causes increased adverse effects on biological systems. The aim of this study was to investigate the effects of EMF on heart tissue by biochemical and histomorphological evaluations in EMF-exposed adult rats. In this study, 28 male Wistar rats weighing 200-250 g were used. The rats were divided into two groups: sham group (n = 14) and EMF group (n = 14). Rats in sham group were exposed to same conditions as the EMF group except the exposure to EMF. Rats in EMF group were exposed to a 50-Hz EMF of 3 mT for 4 h/day and 7 days/week for 2 months. After 2 months of exposure, rats were killed; the hearts were excised and evaluated. Determination of oxidative stress parameters was performed spectrophotometrically. To detect apoptotic cells, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and caspase-3 immunohistochemistry were performed. In EMF-exposed group, levels of lipid peroxidation significantly increased and activities of superoxide dismutase and glutathione peroxidase decreased compared with sham group. The number of TUNEL-positive cells and caspase-3 immunoreactivity increased in EMF exposed rats compared with sham. Under electron microscopy, there were mitochondrial degeneration, reduction in myofibrils, dilated sarcoplasmic reticulum and perinuclear vacuolization in EMF-exposed rats. In conclusion, the results show that the exposure to EMF causes oxidative stress, apoptosis and morphologic damage in myocardium of adult rats. The results of our study indicate that EMF-related changes in rat myocardium could be the result of increased oxidative stress. Further studies are needed to demonstrate whether the exposure to EMF can induce adverse effects on myocardium. PMID- 22323477 TI - In vitro evaluation of the protective effects of 4-thujanol against mitomycin-C and cyclophosphamide-induced genotoxic damage in human peripheral lymphocytes. AB - 4-Thujanol (sabinene hydrate), a bicyclic monoterpene alcohol, is found in the essential oils of many aromatic and medicinal plants and is widely used as a fragrance and flavouring agent in many different products. The aim of this study was to evaluate the protective effects of 4-thujanol against the genotoxic effects induced by mitomycin C (MMC) and cyclophosphamide (CP) in human lymphocytes, using the chromosome aberrations, sister chromatid exchanges, and micronucleus tests, in the absence and in the presence of S9 mix, respectively. The cells were treated with 0.25 ug/mL MMC and 28 ug/mL CP as alone and cotreated with 13 + 0.25, 26 + 0.25, and 52 + 0.25 ug/mL 4-thujanol + MMC and with 13 + 28, 26 + 28, and 52 + 28 ug/mL 4-thujanol + CP as a mixture. The present study showed that 4-thujanol was unable to reduce the genetic damage induced by MMC, in the absence of S9 mix. On the other hand, probably the metabolites of 4-thujanol act as an antagonist and markedly antagonize CP-induced genotoxicity, in the presence of S9 mix. In general, 4-thujanol + MMC and 4-thujanol + CP decreased the mitotic index, proliferation index and nuclear division index to the same extent or more than those of individual exposure of MMC or CP. In conclusion, 4-thujanol significantly reduced (p < 0.001) the genotoxic damage induced by CP but not MMC when compared with the respective positive control alone. We can suggest that 4 thujanol may improve the chemopreventive effects and may also reduce the harmful side effects of CP, which is widely used in chemotherapy against cancer, without reducing its antiproliferative activities. PMID- 22323478 TI - Effect of refinery waste effluent on tocopherol, carotenoid, phenolics and other antioxidants content in Allium cepa. AB - Pollution in water used for irrigation is a major cause of stress generation in plant system. Under these stress conditions, reactive oxygen species derived from molecular oxygen can accumulate in plant, resulting in the oxidation of nucleic acids, lipids, chlorophyll and so on. This study was conducted in Allium cepa to analyze the alteration in the levels of nonenzymatic antioxidants as a consequence of Mathura refinery waste water (MRWW) exposure. The studied antioxidants were glutathione (GSH) and ascorbic acid (ASC). Their determination was carried out in A. cepa bulbs exposed to different concentrations of MRWW that is 0.25*, 0.5*, 0.75* and 1.0*. A significant increase in the levels of these nonenzymatic antioxidants in onion bulbs upon treatment with MRWW suggested that these can serve as suitable biomarkers of toxicity. The toxicity of waste water was also tested on the level of tocopherol (Toc) and carotenoid (CAR) in onion bulbs, and in both the cases a high level of these metabolites was noticed. Phenolic content of A. cepa after the waste water insult was found to be increased, again a manifestation of adaptation against heavy metal and oxidative stress. It is clear from our findings that GSH, ASC, Toc and CAR in A. cepa system could serve as potential biomarkers for the presence of toxicants like heavy metals and its hazards in MRWW. The test waste water demonstrated profound effects on these parameters which is suggestive of the warrior strategies adopted by the plant system against the pollution-induced stress. PMID- 22323479 TI - Genome-wide analysis of STAT3 binding in vivo predicts effectors of the anti inflammatory response in macrophages. AB - Inflammation is a powerful response of the immune system against invading pathogens, and must be cancelled when unneeded or otherwise death inevitably follows. In macrophages, the anti-inflammatory response (AIR) is driven by STAT3 upon IL-10 signaling. The role of STAT3 is to stimulate the expression of specific genes that in-turn suppress the transcription of proinflammatory genes. Here we describe a systematic approach to identify the elusive STAT3-controlled effectors of the AIR. In vivo STAT3-binding sites were identified by ChIP-seq, coupled to expression analysis by RNA-seq, both in resting and IL-10-treated peritoneal macrophages. We report the genomic targets of STAT3 and show that STAT3's transcriptional program during the AIR is highly specific to IL-10 stimulated macrophages, that STAT3 is a positive transcriptional regulator, and we predict severalputative AIR factors that merit further investigation. This is the first in-depth study of the AIR by next-generation sequencing and provides an unprecedented degree of detail into this fundamental physiologic response. PMID- 22323480 TI - Mutations in the spliceosome machinery, a novel and ubiquitous pathway in leukemogenesis. AB - Myelodysplastic syndromes (MDSs) are chronic and often progressive myeloid neoplasms associated with remarkable heterogeneity in the histomorphology and clinical course. Various somatic mutations are involved in the pathogenesis of MDS. Recently, mutations in a gene encoding a spliceosomal protein, SF3B1, were discovered in a distinct form of MDS with ring sideroblasts. Whole exome sequencing of 15 patients with myeloid neoplasms was performed, and somatic mutations in spliceosomal genes were identified. Sanger sequencing of 310 patients was performed to assess phenotype/genotype associations. To determine the functional effect of spliceosomal mutations, we evaluated pre-mRNA splicing profiles by RNA deep sequencing. We identified additional somatic mutations in spliceosomal genes, including SF3B1, U2AF1, and SRSF2. These mutations alter pre mRNA splicing patterns. SF3B1 mutations are prevalent in low-risk MDS with ring sideroblasts, whereas U2AF1 and SRSF2 mutations are frequent in chronic myelomonocytic leukemia and advanced forms of MDS. SF3B1 mutations are associated with a favorable prognosis, whereas U2AF1 and SRSF2 mutations are predictive for shorter survival. Mutations affecting spliceosomal genes that result in defective splicing are a new leukemogenic pathway. Spliceosomal genes are probably tumor suppressors, and their mutations may constitute diagnostic biomarkers that could potentially serve as therapeutic targets. PMID- 22323481 TI - N-cadherin in osteolineage cells is not required for maintenance of hematopoietic stem cells. AB - There is evidence suggesting that N-cadherin expression on osteoblast lineage cells regulates hematopoietic stem cell (HSC) function and quiescence. To test this hypothesis, we conditionally deleted N-cadherin (Cdh2) in osteoblasts using Cdh2(flox/flox) Osx-Cre mice. N-cadherin expression was efficiently ablated in osteoblast lineage cells as assessed by mRNA expression and immunostaining of bone sections. Basal hematopoiesis is normal in these mice. In particular, HSC number, cell cycle status, long-term repopulating activity, and self-renewal capacity were normal. Moreover, engraftment of wild-type cells into N-cadherin deleted recipients was normal. Finally, these mice responded normally to G-CSF, a stimulus that mobilizes HSCs by inducing alterations to the stromal micro environment. In conclusion, N-cadherin expression in osteoblast lineage cells is dispensable for HSC maintenance in mice. PMID- 22323482 TI - Early matched sibling hematopoietic cell transplantation for adult AML in first remission using an age-adapted strategy: long-term results of a prospective GOELAMS study. AB - The LAM2001 phase 3 trial, involving 832 patients with acute myeloid leukemia (AML; median: 46 years) proposed HLA-identical sibling allograft HSCT for all patients with an identified donor. The trial compared reduced-intensity conditioning (RIC) for patients older than 50 years of age (N = 47) and myeloablative conditioning for younger patients (N = 117). BM HSCT was performed in the younger patients, while the older ones received a consolidation course, followed by peripheral blood allo-HSCT using RIC. The incidence of grade II-IV acute GVHD, was 51.9% (95% confidence interval [CI]: 42.1-61.8) and 11.3% (1.6 21.2) after myeloablative or RIC, respectively (P < .0001) and that of chronic GVHD 45.8% (95% CI: 34.8-56.7) and 41.7% (24.7-58.6; NS). Cumulative incidence of nonrelapse mortality at 108 months was 15.8% (95% CI: 9.8-23.2) for myeloablative, and 6.5% (0.2-16.2) for RIC (NS). CI of relapse at 108 months was 21.7% (95% CI: 13.9-28.6) and 28.6% (16.5-43.4; NS). Overall survival at 108 months was 63.4% (95% CI: 54.6-72.2) and 65.8% (52.2-72.2), respectively, after myeloablative or RIC (NS). RIC peripheral blood stem cell allo-HSCT is prospectively feasible for patients between the ages of 51 and 60 years without excess of relapse or nonrelapse mortality, and compares favorably with myeloablative marrow allo-HSCT proposed to younger patients. PMID- 22323483 TI - A review of second primary malignancy in patients with relapsed or refractory multiple myeloma treated with lenalidomide. AB - In a retrospective pooled analysis of 11 clinical trials of lenalidomide-based therapy for relapsed/refractory multiple myeloma (MM; N = 3846), the overall incidence rate (IR, events per 100 patient-years) of second primary malignancies (SPMs) was 3.62. IR of invasive (hematologic and solid tumor) SPMs was 2.08, consistent with the background incidence of developing cancer. In a separate analysis of pooled data from pivotal phase 3 trials of relapsed or refractory MM (N = 703), the overall IR of SPMs was 3.98 (95% confidence interval [CI], 2.51 6.31) with lenalidomide/dexamethasone and 1.38 (95% CI, 0.44-4.27) with placebo/dexamethasone; IRs of nonmelanoma skin cancers were 2.40 (95% CI, 1.33 4.33) and 0.91 (95% CI, 0.23-3.66), respectively; IRs of invasive SPMs were 1.71 (95% CI, 0.86-3.43) and 0.91 (95% CI, 0.23-3.66), respectively. The risk of SPMs must be taken into account before initiating lenalidomide treatment. In the context of the observed survival benefit in relapsed or refractory MM patients, the benefit/risk profile of lenalidomide/dexamethasone remains positive. PMID- 22323484 TI - Antiangiogenic activity of aganirsen in nonhuman primate and rodent models of retinal neovascular disease after topical administration. AB - PURPOSE: Aganirsen, an antisense oligonucleotide inhibiting insulin receptor substrate (IRS)-1 expression, has been shown to promote the regression of pathologic corneal neovascularization in patients. In this study, the authors aimed to demonstrate the antiangiogenic activity of aganirsen in animal models of retinal neovascularization. METHODS: Eyedrops of aganirsen were applied daily in nonhuman primates after laser-induced choroidal neovascularization (CNV; model of wet age-related macular degeneration [AMD]) and in newborn rats after oxygen induced retinopathy (OIR; model of ischemic retinopathy). Retinal aganirsen concentrations were assessed in rabbits and monkeys after topical delivery (21.5, 43, or 86 MUg). Clinical significance was further evaluated by determination of IRS-1 expression in monkey and human retinal biopsy specimens. RESULTS: Topical corneal application of aganirsen attenuated neovascular lesion development dose dependently in African green monkeys. The incidence of high-grade CNV lesions (grade IV) decreased from 20.5% in vehicle-treated animals to 1.7% (P < 0.05) at the 86-MUg dose. Topical aganirsen inhibited retinal neovascularization after OIR in rats (P < 0.05); furthermore, a single intravitreal injection of aganirsen reduced OIR as effectively as ranibizumab, and their effects were additive. Significantly, topical applications of aganirsen did not interfere with physiological retinal vessel development in newborn rats. Retinal delivery after topical administration was confirmed, and retinal expression of IRS-1 was demonstrated to be elevated in patients with subretinal neovascularization and AMD. CONCLUSIONS: Topical application of aganirsen offers a safe and effective therapy for both choroidal and retinal neovascularization without preventing its normal vascularization. Together, these findings support the clinical testing of aganirsen for human retinal neovascular diseases. PMID- 22323485 TI - Effect of blur adaptation on human parafoveal vision. AB - PURPOSE: This study was conducted to investigate whether neural compensation for induced defocus can alter visual resolution in other areas of the human retina beyond the fovea. In certain circumstances, the blur adaptation response may be influenced by refractive status. METHODS: The effect of blur adaptation on the central 10 degrees of the retina was investigated in 20 normally sighted observers (10 emmetropes and 10 myopes; median age, 21 years). Visual acuity (VA) was measured at the fovea and at five locations of the parafoveal nasal visual field (2 degrees , 4 degrees , 6 degrees , 8 degrees , and 10 degrees ) with best corrected distance vision. Myopic defocus of 1 D was introduced, and the same measurements were repeated immediately before and after a 30-minute adaptation. RESULTS: VA declined with increasing eccentricity in the clear, blurred, and blur adapted viewing conditions. The rate of decline was quantified by the parameter E2, which represents the amount of eccentricity dependence of the acuity task. Foveal and parafoveal VA decreased with the introduction of optical defocus and improved significantly after a period of blur adaptation. The consistent value of E2 in each condition indicated that these changes in VA were not eccentricity dependent. Changes in VA under blurred and blur-adapted conditions were of similar magnitudes in myopic and emmetropic observers. CONCLUSIONS: Neural adaptation to blur improves VA under defocused conditions in the parafovea as well as the fovea, indicating that the underlying compensatory mechanism acts across a range of spatial scales and independently of retinal eccentricity. Foveal and parafoveal blur adaptation does not vary with refractive error. PMID- 22323486 TI - Netrin-1 simultaneously suppresses corneal inflammation and neovascularization. AB - PURPOSE: To investigate the effect of netrin-1 on alkali burn-induced corneal inflammation and neovascularization. METHODS: The expression of netrin-1 and its receptors UNC5A, UNC5B, UNC5C, UNC5D, adenosine 2b receptor (A2BAR), deleted in colorectal cancer (DCC), and neogenin in normal and alkali-burned rat cornea were determined by RT-PCR and/or Western blot analysis, or immunostaining. Topical netrin-1 protein was applied to treat rat corneal alkali-burn injury for 14 consecutive days, started right after the injury or 10 days postinjury. Corneal inflammation and neovascularization were observed under slit lamp microscope. The apoptosis of corneal cells was determined by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. Corneal inflammatory cell infiltration was evaluated by immunostaining of anti-PMN and anti-ED1 antibodies. The expression of epidermal growth factor (EGF), vascular epidermal growth factor (VEGF), and pigment epithelium-derived factor (PEDF) in rat cornea was determined by Western blot analysis. RESULTS: Netrin-1 and its receptor UNC5B were expressed in normal rat corneal epithelium and stromal cells, and their expression decreased after corneal alkali burn. Exogenous netrin-1 administered on rat ocular surfaces resolved alkali burn-induced corneal inflammation, and also suppressed corneal neovascularization. Furthermore, netrin-1 could reverse neovascularization in alkali-burned cornea. The authors found that netrin-1 executed the functions through various mechanisms, including upregulating EGF expression, accelerating epithelial wound healing, inhibiting neutrophil and macrophage infiltration, reducing corneal cell apoptosis, and restoring the equilibrium of VEGF and PEDF in the wounded cornea. CONCLUSIONS: Netrin-1 could dampen inflammation, inhibit, and reverse neovascularization in alkali-burned cornea. PMID- 22323487 TI - Transplantation of cultivated oral mucosal epithelium prepared in fibrin-coated culture dishes. AB - PURPOSE: To compare the clinical results of cultivated oral mucosal epithelial cell sheet transplantation (COMET) of substrate-free sheets with those of COMET of amniotic membrane (AM)-based sheets. METHODS: Sixteen eyes receiving COMET of substrate-free sheets (substrate-free group) were studied retrospectively and compared with disease-, age-, and ocular surface status-matched eyes undergoing COMET with AM serving as the substrate (AM group). Each group consisted of six eyes with chemical injury, six with pseudo-ocular cicatricial pemphigoid, two with Stevens-Johnson syndrome, and two with ocular cicatricial pemphigoid. Graft survival rate, best-corrected visual acuity (BCVA), and neovascularization (NV) were assessed. RESULT: In all 32 eyes, the entire corneal surface on which the cultivated autologous oral mucosal epithelium sheet had been placed was free of epithelial defects at postoperative day 2. The success rates of COMET at 12 months after surgery were 62.5% in the substrate-free sheet group and 43.8% in the AM group. A Kaplan-Meier curve revealed that the graft survival rate in the substrate-free group was significantly superior to that in the AM group (P = 0.046). Mean postoperative BCVA improved significantly at 1, 3, and 6 months in the substrate-free sheet group, and BCVA was significantly better than that in the AM group at all time points. Postoperative NV improved significantly in the substrate-free group at all time points. CONCLUSIONS: A better midterm clinical outcome was achieved with COMET of a substrate-free cell sheet than with COMET of AM as a substrate for treating severe stem cell deficiency. PMID- 22323488 TI - The effect of daily transient +4 D positive lens wear on the inhibition of myopia in the tree shrew. AB - PURPOSE: Negative-lens-induced defocus causes accelerated ocular elongation and myopia, whereas positive-lens-induced defocus produces reduced ocular elongation and hyperopia. Short durations of positive lens wear result in markedly stronger temporal effects than do short periods of negative lens wear in the chick model of refractive development. In mammalian and nonhuman primate models, there have been equivocal results in inhibiting myopia by short periods of positive lens wear when compared with data from the chick model. The purpose of the present study was an evaluation of full-time -9.5 D negative lens wear interrupted by short periods of daily +4 D positive lens wear in preventing experimental myopia in the tree shrew. METHODS: One treatment group wore negative lenses (-9.5 D) binocularly for 23 hours a day (10 hours of which were spent in total darkness), interrupted by 1 hour of wearing positive lenses (+4 D) binocularly for 12 days. Another group of animals wore negative lenses (-9.5 D) binocularly for 23 hours a day, interrupted by two 30-minute periods of positive lens (+4 D) wear daily, again for 12 days. The animals were raised on a 14-hour/10-hour light-dark cycle. Animals wearing -9.5 D lenses binocularly, interrupted by 0-powered lenses for either 1 hour or two 30-minute periods daily for 12 days, acted as controls. RESULTS: Continuous wear of -9.5 D lenses binocularly induced a -10.8 D myopic shift in refraction. Full-time wear of -9.5 D lenses binocularly, interrupted by 1 hour of 0-power lens wear binocularly, caused a myopic shift of 3.6 D over 12 days, whereas wearing -9.5 D lenses, interrupted by 1 hour every day of +4.0 D lens wear binocularly, whether it was continuous or divided into two 30-minute periods, caused a myopic shift of only 0.7 D over 12 days. CONCLUSIONS: Daily intermittent +4 D positive lens wear effectively inhibits experimentally induced myopia and may prove a viable approach for preventing myopia progression in children. PMID- 22323489 TI - Complement and UV-irradiated photoreceptor outer segments increase the cytokine secretion by retinal pigment epithelial cells. AB - PURPOSE: Age-related macular degeneration (AMD) is accompanied by increased complement activation, and by lipofuscin accumulation in retinal pigment epithelial (RPE) cells due to incomplete degradation of photoreceptor outer segments (POS). The influence of POS, ultraviolet (UV)-irradiated POS and human complement sera (HCS) on cytokine secretion from RPE cells was therefore examined. METHODS: RPE cells were incubated with POS or UV-POS every other day for 1 week. The autofluorescence (AF) was measured photometrically and by flow cytometry. Senescence-associated genes were analyzed by RT-PCR. Internalization and degradation of POS were determined using phagocytosis and degradation assays, and lysosomal function by neutral red uptake. RPE cells in polycarbonate cell culture inserts were incubated apically with POS or UV-POS and afterward basally with HCS. C7-deficient HCS was used as control. The integrity of the cell monolayer was assessed by measuring the transepithelial electrical resistance (TER) and the permeability. Interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1, and vascular endothelial growth factor were quantified by ELISA. RESULTS: POS treatment led to an increased AF and senescence marker expression, which were further elevated in response to UV-POS. UV-POS were preferentially accumulated over POS and the lysosomal function was impaired due to UV-POS. HCS intensified the cytokine production compared with controls. POS had no effect, though UV-POS combined with HCS induced a significant increase in all cytokines. CONCLUSIONS: RPE cultivation with UV-POS might serve as a model to investigate the accumulation of lipofuscin-like structures. The enhanced cytokine secretion due to UV-POS with HCS may account for an increased susceptibility for lipofuscin loaded cells to complement, inducing a proinflammatory environment as observed in AMD. PMID- 22323490 TI - Faculty of Public Health calls for the health bill to be withdrawn. PMID- 22323491 TI - Charity backtracks on cuts to Planned Parenthood funding. PMID- 22323492 TI - Care home resident challenges PCT's right to hive off services to a social enterprise without a proper tendering process. PMID- 22323495 TI - Mitral valve repair for severe mitral regurgitation secondary to lone atrial fibrillation. AB - OBJECTIVES: Significant mitral regurgitation (MR) may arise from isolated annular dilatation secondary to lone atrial fibrillation (AF) and associated atrial remodelling. The aim of the present study is to assess the outcome of surgery for this condition. METHODS: Between November 2007 and July 2011, 20 patients underwent mitral valve (MV) repair for severe MR secondary to AF. The median age of patients was 77.5 years (45-82 years) and the mean pre-operative duration of AF was 84.6 +/- 92 months. The left ventricle was moderately (ejection fraction 30-50%; n = 6) or severely (<30%; n = 1) impaired in seven patients pre operatively. Mean logistic EuroSCORE was 8.1 +/- 5.9 and mean follow-up was 18.0 +/- 12.5 months. RESULTS: All operations were elective. Concomitant anti arrhythmic procedures (maze procedure, pulmonary vein isolation) or left atrial (LA) appendage amputation were performed in all patients; tricuspid valve repair was undertaken in 12 patients and coronary artery bypass grafting in 2 patients. Ring annuloplasty was performed in all patients. The median ring size was 30 mm (range 24-36 mm). On-table transoesophageal echocardiography post-repair showed mild residual MR in two patients and no MR in the remainder. There were no cases of systolic anterior motion. There was one re-exploration for bleeding. No patients required haemofiltration or suffered from stroke and deep sternal wound infections. There was no in-hospital mortality. At discharge mean left ventricular (LV) end-diastolic diameter was 4.8 +/- 0.7 cm compared with 5.6 +/- 0.7 cm pre-operatively (P < 0.005), while mean LV end-systolic diameter was 3.2 +/- 0.8 cm when compared with 4.0 +/- 0.7 cm pre-operatively (P < 0.005). The mean LA size was 5.2 +/- 1.0 cm when compared with 6.1 +/- 1.6 cm pre-operatively (P = 0.03). There was mild MR in two patients, but none in the rest. The mean MV area was 3.0 +/- 0.7 cm(2). The mean systolic pulmonary artery pressure was 40.4 +/- 15.5 mmHg when compared with 54.1 +/- 12.2 mmHg pre-operatively (P = 0.02). Seventeen patients (85%) were in NYHA class I/II at latest follow-up (P < 0.0001 vs pre-operatively). During follow-up, there were no thrombo-embolic complications, re-operation, endocarditis or deaths. CONCLUSIONS: MV annuloplasty for annular dilatation secondary to AF has a good mid-term outcome. PMID- 22323494 TI - Rationale behind targeting fibroblast activation protein-expressing carcinoma associated fibroblasts as a novel chemotherapeutic strategy. AB - The tumor microenvironment has emerged as a novel chemotherapeutic strategy in the treatment of cancer. This is most clearly exemplified by the antiangiogenesis class of compounds. Therapeutic strategies that target fibroblasts within the tumor stroma offer another treatment option. However, despite promising data obtained in preclinical models, such strategies have not been widely used in the clinical setting, largely due to a lack of effective treatments that specifically target this population of cells. The identification of fibroblast activation protein alpha (FAP) as a target selectively expressed on fibroblasts within the tumor stroma or on carcinoma-associated fibroblasts led to intensive efforts to exploit this novel cellular target for clinical benefit. FAP is a membrane-bound serine protease of the prolyl oligopeptidase family with unique post-prolyl endopeptidase activity. Until recently, the majority of FAP-based therapeutic approaches focused on the development of small-molecule inhibitors of enzymatic activity. Evidence suggests, however, that FAP's pathophysiological role in carcinogenesis may be highly contextual, depending on both the exact nature of the tumor microenvironment present and the cancer type in question to determine its tumor-promoting or tumor-suppressing phenotype. As an alternative strategy, we are taking advantage of FAP's restricted expression and unique substrate preferences to develop a FAP-activated prodrug to target the activation of a cytotoxic compound within the tumor stroma. Of note, this strategy would be effective independently of FAP's role in tumor progression because its therapeutic benefit would rely on FAP's localization and activity within the tumor microenvironment rather than strictly on inhibition of its function. PMID- 22323496 TI - Ten-year experience of mediastinal robotic surgery in a single referral centre. AB - OBJECTIVE: The aim of this study was to report a single referral centre experience in the exeresis of mediastinal lesions with robotic surgical system. The outcomes of all patients were retrospectively investigated with special regard to myasthenic and thymomatous patients. METHODS: From February 2001 to December 2010, 69 patients (30 males, 39 females), with a mean age of 55.4 years (range 20-81), underwent robotic surgery for treatment of mediastinal lesions. There were 39 thymectomies, 13 paravertebral neurogenic tumour removals, 9 pleuropericardial cyst removals, 3 teratoma excisions, 4 lymphonodal removals and 1 enterogenous cyst excision. Operative time, conversion rate, morbidity and mortality were analysed. RESULTS: There were no intra-operative complications, and no mortality. The mean operative time was 124.3 min (range 45-240). Conversion to open surgery occurred in three cases (4.3%). All post-operative complications (7.2%) were conservatively treated. The mean post-operative stay was 4.3 days (range 3-10). For the myasthenic patients (mean follow-up of 18 months), the Myasthenia Gravis Foundation of America change in status resulted improved in 18 (90%) patients and unchanged in 2 (10%) patients. In cases of thymoma, the pathological analysis revealed Masaoka stage I (seven cases), IIA (three cases), IIB (two cases) and III (one case). No disease recurrence occurred at a mean follow-up of 16 months. CONCLUSIONS: Our experience suggests that the surgical system was safe in performing mediastinal mass resection, with low morbidity and conversion rate. The robotic system proved useful, especially in a tiny space such as the mediastinum, and appeared to be an effective treatment for myasthenia gravis and for early-stage thymoma. PMID- 22323497 TI - A novel technique for pulmonary endarterectomy in the presence of patent coronary artery bypass grafts. AB - Pulmonary endarterectomy (PEA) is the definitive surgical treatment for chronic thromboembolic pulmonary hypertension, with excellent short- and long-term results. PEA following previous coronary artery bypass graft surgery carries a risk of damage to patent grafts, as well as the risk of inadequate myocardial protection, especially when a patent pedicled internal thoracic artery graft is present. We report a technique where PEA may be safely and successfully accomplished ensuring, adequate clearance of bilateral pulmonary thromboembolic disease via a right pulmonary arteriotomy, avoiding the patent bypass grafts overlying the pulmonary trunk, while ensuring adequate myocardial protection. PMID- 22323498 TI - Regulation of interferon-inducible proteins by doxorubicin via interferon gamma Janus tyrosine kinase-signal transducer and activator of transcription signaling in tumor cells. AB - Activation of the immune system is a way for host tissue to defend itself against tumor growth. Hence, treatment strategies that are based on immunomodulation are on the rise. Conventional cytostatic drugs such as the anthracycline doxorubicin can also activate immune cell functions of macrophages and natural killer cells. In addition, cytotoxicity of doxorubicin can be enhanced by combining this drug with the cytokine interferon-gamma (IFNgamma). Although doxorubicin is one of the most applied cytostatics, the molecular mechanisms of its immunomodulation ability have not been investigated thoroughly. In microarray analyses of HeLa cells, a set of 19 genes related to interferon signaling was significantly over represented among genes regulated by doxorubicin exposure, including signal transducer and activator of transcription (STAT) 1 and 2, interferon regulatory factor 9, N-myc and STAT interactor, and caspase 1. Regulation of these genes by doxorubicin was verified with real-time polymerase chain reaction and immunoblotting. An enhanced secretion of IFNgamma was observed when HeLa cells were exposed to doxorubicin compared with untreated cells. IFNgamma-neutralizing antibodies and inhibition of Janus tyrosine kinase (JAK)-STAT signaling [aurintricarboxylic acid (ATA), (E)-2-cyano-3-(3,4-dihydrophenyl)-N (phenylmethyl)-2-propenamide (AG490), STAT1 small interfering RNA] significantly abolished doxorubicin-stimulated expression of interferon signaling-related genes. Furthermore, inhibition of JAK-STAT signaling significantly reduced doxorubicin-induced caspase 3 activation and desensitized HeLa cells to doxorubicin cytotoxicity. In conclusion, we demonstrate that doxorubicin induces interferon-responsive genes via IFNgamma-JAK-STAT1 signaling and that this pathway is relevant for doxorubicin's cytotoxicity in HeLa cells. Immunomodulation is a promising strategy in anticancer treatment, so this novel mode of action of doxorubicin may help to further improve the use of this drug among different types of anticancer treatment strategies. PMID- 22323499 TI - In vitro interference of tigecycline at subinhibitory concentrations on biofilm development by Enterococcus faecalis. AB - OBJECTIVES: Since biofilm formation is the hallmark of Enterococcus faecalis isolates, the aim of this study was to quantify biofilm formation in the presence of subinhibitory concentrations of tigecycline. METHODS: Interference of tigecycline on biofilm formation was spectrophotometrically quantified using 20 biofilm-producing E. faecalis isolates with tigecycline MICs of 0.12 (8 strains) or 0.25 mg/L (12 strains). Biofilm production was measured in antibiotic-free tryptic soy broth supplemented with 1% glucose and compared with biofilm production in the same medium with tigecycline at subinhibitory concentrations (0.25* or 0.5* MIC, similar to trough concentrations in serum or concentrations in the colon after a standard dose) by reading the optical density at 450 nm (OD(450)) after staining with Crystal Violet. RESULTS: In the presence of subinhibitory tigecycline concentrations, pooled OD(450) values for the 20 strains [median (IQR)] were significantly lower than those for controls: 0.468 (0.379-0.516) for antibiotic-free controls versus 0.295 (0.200-0.395) for 0.25* MIC tigecycline (P < 0.001) and 0.287 (0.245-0.479) for 0.5* MIC tigecycline (P < 0.001), with significant differences between pooled OD(450) values obtained with each concentration of tigecycline (P = 0.022). In 17 out of 20 (85%) strains the OD(450) obtained with 0.25* MIC tigecycline was significantly (P < 0.05) lower than the basal OD(450), while this occurred in 12 out of 20 (60%) strains with 0.5* MIC. CONCLUSIONS: In vitro tigecycline subinhibitory concentrations were able to interfere with biofilm formation by E. faecalis. PMID- 22323500 TI - Escherichia coli with extended-spectrum beta-lactamase and plasmid-mediated quinolone resistance genes in great cormorants and mallards in Central Europe. AB - OBJECTIVES: Faecal Escherichia coli strains were isolated from great cormorants (Phalacrocorax carbo) and mallards (Anas platyrhynchos), which are commonly occurring waterbirds in Europe, and studied for resistance to cephalosporins and fluoroquinolones. METHODS: Cloacal swabs or faeces from great cormorants and mallards in Central Europe were cultivated to isolate Escherichia coli strains with extended-spectrum beta-lactamase (ESBL) and plasmid-mediated quinolone resistance (PMQR) genes. RESULTS: Ten ESBL-producing E. coli with the bla(CTX-M 15) or bla(CTX-M-27) gene were isolated from eight great cormorants (1.6%, n = 499). The bla(CTX-M) genes were harboured by plasmids of F and I1 incompatibility groups. CTX-M-27-producing isolates were identified as the epidemiologically important B2-O25b-ST131 clone. No ESBL-producing E. coli was isolated from 305 mallards. Eight E. coli isolates with PMQR genes [six aac(6')-Ib-cr and two qnrS1] were detected in six great cormorants (1.2%). Seventeen strains with qnrS1 were detected in 17 mallards (6%). The PMQR genes were located on plasmids of incompatibility groups F, N or X2. ESBL and PMQR genes were found on conjugative plasmids, enabling the horizontal spread of resistance. CONCLUSIONS: Both great cormorants and mallards can spread epidemiologically important antimicrobial resistant E. coli isolates to water bodies throughout Europe. PMID- 22323501 TI - Recombinant human interleukin 28B: anti-HCV potency, receptor usage and restricted cell-type responsiveness. AB - OBJECTIVES: Interleukin 28B (IL28B) genetic variation has been recently reported as a potent predictor of hepatitis C virus (HCV) response to interferon (IFN) therapy. The aim of this study was to produce recombinant human IL28B (rhIL28B) in yeast and explore the action mechanisms of rhIL28B as a novel anti-HCV agent. METHODS: A simple and efficient protocol for producing rhIL28B in the methylotrophic yeast Pichia pastoris was developed. The anti-HCV activity, induction of IFN-stimulated genes (ISGs), receptor usage and cellular responsiveness of rhIL28B were characterized. RESULTS: The yield of secreted rhIL28B was optimized to 200 mg/L, and soluble rhIL28B that was approximately 95% pure was achieved using a one-step ion-exchange purification procedure. rhIL28B inhibited HCV propagation in Huh7.5.1 cells with an IC(50) of 0.15 * 10(-3) mg/L. Treatment of hepatoma cells with rhIL28B resulted in the phosphorylation of STAT1 within 1 h and expression of ISGs. The HCV inhibitory effects of rhIL28B were antagonized by the antibody neutralization of receptors IL10R2 and IL28R1. The combination of rhIL28B and ribavirin synergistically inhibited HCV production in cell culture. Importantly, compared with the broad-spectrum activity of IFN alpha, we demonstrated restricted cell-type responsiveness of rhIL28B in liver, lung and prostate cells. CONCLUSIONS: This study established an easy and highly efficient approach for the production of rhIL28B with potent in vitro antiviral activity and restricted cell tropism, and thus provides a novel antiviral candidate for improving the treatment of HCV-infected patients. PMID- 22323502 TI - Acute cannabis consumption and motor vehicle collision risk: systematic review of observational studies and meta-analysis. AB - OBJECTIVE: To determine whether the acute consumption of cannabis (cannabinoids) by drivers increases the risk of a motor vehicle collision. DESIGN: Systematic review of observational studies, with meta-analysis. DATA SOURCES: We did electronic searches in 19 databases, unrestricted by year or language of publication. We also did manual searches of reference lists, conducted a search for unpublished studies, and reviewed the personal libraries of the research team. Review methods We included observational epidemiology studies of motor vehicle collisions with an appropriate control group, and selected studies that measured recent cannabis use in drivers by toxicological analysis of whole blood or self report. We excluded experimental or simulator studies. Two independent reviewers assessed risk of bias in each selected study, with consensus, using the Newcastle-Ottawa scale. Risk estimates were combined using random effects models. RESULTS: We selected nine studies in the review and meta-analysis. Driving under the influence of cannabis was associated with a significantly increased risk of motor vehicle collisions compared with unimpaired driving (odds ratio 1.92 (95% confidence interval 1.35 to 2.73); P=0.0003); we noted heterogeneity among the individual study effects (I(2)=81). Collision risk estimates were higher in case control studies (2.79 (1.23 to 6.33); P=0.01) and studies of fatal collisions (2.10 (1.31 to 3.36); P=0.002) than in culpability studies (1.65 (1.11 to 2.46); P=0.07) and studies of non-fatal collisions (1.74 (0.88 to 3.46); P=0.11). CONCLUSIONS: Acute cannabis consumption is associated with an increased risk of a motor vehicle crash, especially for fatal collisions. This information could be used as the basis for campaigns against drug impaired driving, developing regional or national policies to control acute drug use while driving, and raising public awareness. PMID- 22323503 TI - Driving while under the influence of cannabis. PMID- 22323504 TI - Disaster waste management challenges. PMID- 22323505 TI - The James Jackson Award. PMID- 22323506 TI - Doctors in Syria are being forced to treat patients in secret, charity says. PMID- 22323507 TI - Peers vote to put mental health on equal footing with physical health in the NHS. PMID- 22323508 TI - Delirium in intensive care patients. PMID- 22323510 TI - Varicose veins. PMID- 22323509 TI - Development and validation of PRE-DELIRIC (PREdiction of DELIRium in ICu patients) delirium prediction model for intensive care patients: observational multicentre study. AB - OBJECTIVES: To develop and validate a delirium prediction model for adult intensive care patients and determine its additional value compared with prediction by caregivers. DESIGN: Observational multicentre study. SETTING: Five intensive care units in the Netherlands (two university hospitals and three university affiliated teaching hospitals). PARTICIPANTS: 3056 intensive care patients aged 18 years or over. MAIN OUTCOME MEASURE: Development of delirium (defined as at least one positive delirium screening) during patients' stay in intensive care. RESULTS: The model was developed using 1613 consecutive intensive care patients in one hospital and temporally validated using 549 patients from the same hospital. For external validation, data were collected from 894 patients in four other hospitals. The prediction (PRE-DELIRIC) model contains 10 risk factors-age, APACHE-II score, admission group, coma, infection, metabolic acidosis, use of sedatives and morphine, urea concentration, and urgent admission. The model had an area under the receiver operating characteristics curve of 0.87 (95% confidence interval 0.85 to 0.89) and 0.86 after bootstrapping. Temporal validation and external validation resulted in areas under the curve of 0.89 (0.86 to 0.92) and 0.84 (0.82 to 0.87). The pooled area under the receiver operating characteristics curve (n=3056) was 0.85 (0.84 to 0.87). The area under the curve for nurses' and physicians' predictions (n=124) was significantly lower at 0.59 (0.49 to 0.70) for both. CONCLUSION: The PRE DELIRIC model for intensive care patients consists of 10 risk factors that are readily available within 24 hours after intensive care admission and has a high predictive value. Clinical prediction by nurses and physicians performed significantly worse. The model allows for early prediction of delirium and initiation of preventive measures. Trial registration Clinical trials NCT00604773 (development study) and NCT00961389 (validation study). PMID- 22323511 TI - Appetite suppressant was probably responsible for 1300 deaths, study shows. PMID- 22323512 TI - A novel aquaporin 3 in killifish (Fundulus heteroclitus) is not an arsenic channel. AB - The Atlantic killifish (Fundulus heteroclitus) is a model environmental organism that has an extremely low assimilation rate of environmental arsenic. As a first step in elucidating the mechanism behind this phenomenon, we used quantitative real-time PCR to identify aquaglyceroporins (AQPs), which are arsenite transporters, in the killifish gill. A novel homolog killifish AQP3 (kfAQP3a) was cloned from the killifish gill, and a second homolog was identified as the consensus from a transcriptome database (kfAQP3b). The two were 99% homologous to each other, 98% homologous to a previously identified killifish AQP3 from embryos (kfAQP3ts), and 78% homologous to hAQP3. Expression of kfAQP3a in Xenopus oocytes significantly enhanced water, glycerol, and urea transport. However, kfAQP3a expressed in HEK293T cells did not transport significant amounts of arsenic. All sequence motifs thought to confer the ability of AQP3 to transport solutes were conserved in kfAQP3a, kfAQP3b, and kfAQP3ts; however, the C-terminal amino acids were different in kfAQP3a versus the other two homologs. Replacement of the three C-terminal amino acids of kfAQP3 (GKS) with the three C-terminal amino acids of kfAQP3b and kfAQP3ts (ANC) was sufficient to enable kfAQP3a to robustly transport arsenic. Thus, the C-terminus of kfAQP3b and kfAQP3ts confers arsenic selectivity in kfAQP3. Moreover, kfAQP3a, the only AQP expressed in killifish gill, is the first aquaglyceroporin identified that does not transport arsenic, which may explain, in part, why killifish poorly assimilate arsenic and are highly tolerant to environmental arsenic. PMID- 22323513 TI - Early exposure to 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) affects mating behavior of zebra finches. AB - 2,2',4,4',5-Pentabromodiphenyl ether (BDE-99) is a brominated flame retardant congener that has pervaded global food chains, being reported in avian egg and tissue samples throughout the world. Its effects on birds are not well known, but there is evidence in exposed mammals that it directly mediates and causes neurotoxicity, alters thyroid hormone homeostasis, and lowers sex steroid hormone concentrations. In birds, those processes could disrupt the song-control system and male mating behavior. In this study, the effects of nestling exposure to environmentally relevant levels of BDE-99 were assessed in a model songbird species, the zebra finch (Taeniopygia guttata). A tissue residue study in which zebra finch nestlings were orally exposed to 0, 2.5, 15.8, or 50.7 ng BDE-99/g body weight (bw) per day over the 21-day nesting period validated dosing methods and confirmed dose levels were environmentally relevant (332.7 +/- 141.0 to 4450.2 +/- 1396.2 ng/g plasma lipid). A full-scale study exposing nestlings to 0, 2.5, 15.8, 50.7, or 173.8 ng BDE-99/g bw/day was carried out to investigate long term effects of BDE-99 on the adult song-control nuclei volumes, song quality, and male mating behavior. Early exposure to BDE-99 had significant effects on male mating behavior and the response of clean experienced females to exposed males. There was no effect on male song-control nuclei or song quality, and there were nondose-dependent effects on female song-control nuclei. The results demonstrate that early exposure to environmentally relevant levels of BDE-99 affects the behavior of zebra finches. PMID- 22323515 TI - Fibrodysplasia induced in dog skin by a matrix metalloproteinase (MMP) inhibitor- a mechanistic analysis. AB - Matrix metalloproteinase (MMP) inhibitors, candidate therapeutic agents for a number of diseases, are known to be associated with acute fibrosis-type adverse effects in a number of species, including humans. The broad-spectrum MMP inhibitor, AZM551248, has previously been shown to cause these effects in the dog. Changes were characterized by the abnormal and extensive proliferation of fibroblasts and the deposition of collagen particularly in the subcutaneous connective tissues (subcutis) and were termed fibrodysplasia (FD). We performed a time-course study in dogs using AZM551248 and sampled skin, subcutis, and plasma before and during the development of FD. Detailed histopathological analysis and global gene expression profiling were performed on the subcutaneous tissues. The gene expression analysis of the subcutis indicated that extracellular matrix (ECM) remodeling was initiated asymptomatically at or before the earliest time point, day 4, and this was associated with dysregulation of expression of a number of MMPs and proteolytic enzymes. At later time points, the FD became progressively more extensive and severe, and this was associated with gene expression changes characteristic of tissue fibrosis, for example those associated with procollagen synthesis and processing. We postulate that AZM551248 inhibition of MMP action within the subcutis modulates the activity of several transcription factors and this in turn upregulates expression of specific proteases which initiate ECM remodeling. Persistent MMP inhibition results in the progression of ECM remodeling, culminating in collagen deposition and overt fibrosis. Our data indicate that inhibition of MMPs 1, 2, 3, and 9 is a key early event in AZM551248-induced FD in dog subcutis. PMID- 22323514 TI - Cobblestone lissencephaly: neuropathological subtypes and correlations with genes of dystroglycanopathies. AB - Cobblestone lissencephaly represents a peculiar brain malformation with characteristic radiological anomalies, defined as cortical dysplasia combined with dysmyelination, dysplastic cerebellum with cysts and brainstem hypoplasia. Cortical dysplasia results from neuroglial overmigration into the arachnoid space, forming an extracortical layer, responsible for agyria and/or 'cobblestone' brain surface and ventricular enlargement. The underlying mechanism is a disruption of the glia limitans, the outermost layer of the brain. Cobblestone lissencephaly is pathognomonic of a continuum of autosomal recessive diseases with cerebral, ocular and muscular deficits, Walker-Warburg syndrome, muscle-eye-brain and Fukuyama muscular dystrophy. Mutations in POMT1, POMT2, POMGNT1, LARGE, FKTN and FKRP genes attributed these diseases to alpha dystroglycanopathies. However, studies have not been able to identify causal mutations in the majority of patients and to establish a clear phenotype/genotype correlation. Therefore, we decided to perform a detailed neuropathological survey and molecular screenings in 65 foetal cases selected on the basis of histopathological criteria. After sequencing the six genes of alpha dystroglycanopathies, a causal mutation was observed in 66% of cases. On the basis of a ratio of severity, three subtypes clearly emerged. The most severe, which we called cobblestone lissencephaly A, was linked to mutations in POMT1 (34%), POMT2 (8%) and FKRP (1.5%). The least severe, cobblestone lissencephaly C, was linked to POMGNT1 mutations (18%). An intermediary type, cobblestone lissencephaly B, was linked to LARGE mutations (4.5%) identified for the first time in foetuses. We conclude that cobblestone lissencephaly encompasses three distinct subtypes of cortical malformations with different degrees of neuroglial ectopia into the arachnoid space and cortical plate disorganization regardless of gestational age. In the cerebellum, histopathological changes support the novel hypothesis that abnormal lamination arises from a deficiency in granule cells. Our studies demonstrate the positive impact of histoneuropathology on the identification of alpha-dystroglycanopathies found in 66% of cases, while with neuroimaging criteria and biological values, mutations are found in 32-50% of patients. Interestingly, our morphological classification was central in the orientation of genetic screening of POMT1, POMT2, POMGNT1, LARGE and FKRP. Despite intensive research, one-third of our cases remained unexplained; suggesting that other genes and/or pathways may be involved. This material offers a rich resource for studies on the affected neurodevelopmental processes of cobblestone lissencephaly and on the identification of other responsible gene(s)/pathway(s). PMID- 22323516 TI - Identification of activated cryptic 5' splice sites using structure profiles and odds measure. AB - The activation of cryptic 5' splice sites (5' SSs) is often related to human hereditary diseases. The DNA-based mutation screening strategies are commonly used to recognize the cryptic 5' SSs, because features of the local DNA sequence can influence the choice of cryptic 5' SSs. To improve the identification of the cryptic 5' SSs, we developed a structure-based method, named SPO (structure profiles and odds measure), which combines two parameters, the structural feature derived from hydroxyl radical cleavage pattern and odds measure, to assess the likelihood of a cryptic 5' SS activation in competing with its paired authentic 5' SS. Compared to the current tools for identifying activated cryptic 5' SSs, the SPO algorithm achieves higher prediction accuracy than the other methods, including MaxEnt, MDD, Markov model, weight matrix model, Shapiro and Senapathy matrix, R(i) and DeltaG. In addition, the predicted DeltaSPO scores from the SPO algorithm exhibited a greater degree of correlation with the strength of cryptic 5' SS activation than that measured from the other seven methods. In conclusion, the SPO algorithm provides an optimal identification of cryptic 5' SSs, can be applied in designing mutagenesis experiments for various splicing events and may be helpful to investigate the relationship between structural variants and human hereditary diseases. PMID- 22323517 TI - The DEAD-box helicase DDX3 supports the assembly of functional 80S ribosomes. AB - The DEAD-box helicase DDX3 has suggested functions in innate immunity, mRNA translocation and translation, and it participates in the propagation of assorted viruses. Exploring initially the role of DDX3 in the life cycle of hepatitis C virus, we observed the protein to be involved in translation directed by different viral internal ribosomal entry sites. Extension of these studies revealed a general supportive role of DDX3 in translation initiation. DDX3 was found to interact in an RNA-independent manner with defined components of the translational pre-initiation complex and to specifically associate with newly assembling 80S ribosomes. DDX3 knock down and in vitro reconstitution experiments revealed a significant function of the protein in the formation of 80S translation initiation complexes. Our study implies that DDX3 assists the 60S subunit joining process to assemble functional 80S ribosomes. PMID- 22323518 TI - A functional assay for microRNA target identification and validation. AB - MicroRNAs (miRNA) are a class of small RNA molecules that regulate numerous critical cellular processes and bind to partially complementary sequences resulting in down-regulation of their target genes. Due to the incomplete homology of the miRNA to its target site identification of miRNA target genes is difficult and currently based on computational algorithms predicting large numbers of potential targets for a given miRNA. To enable the identification of biologically relevant miRNA targets, we describe a novel functional assay based on a 3'-UTR-enriched library and a positive/negative selection strategy. As proof of principle we have used mir-130a and its validated target MAFB to test this strategy. Identification of MAFB and five additional targets and their subsequent confirmation as mir-130a targets by western blot analysis and knockdown experiments validates this strategy for the functional identification of miRNA targets. PMID- 22323519 TI - The global repressor FliZ antagonizes gene expression by sigmaS-containing RNA polymerase due to overlapping DNA binding specificity. AB - FliZ, a global regulatory protein under the control of the flagellar master regulator FlhDC, was shown to antagonize sigma(S)-dependent gene expression in Escherichia coli. Thereby it plays a pivotal role in the decision between alternative life-styles, i.e. FlhDC-controlled flagellum-based motility or sigma(S)-dependent curli fimbriae-mediated adhesion and biofilm formation. Here, we show that FliZ is an abundant DNA-binding protein that inhibits gene expression mediated by sigma(S) by recognizing operator sequences that resemble the -10 region of sigma(S)-dependent promoters. FliZ does so with a structural element that is similar to region 3.0 of sigma(S). Within this element, R108 in FliZ corresponds to K173 in sigma(S), which contacts a conserved cytosine at the 13 promoter position that is specific for sigma(S)-dependent promoters. R108 as well as C(-13) are also crucial for DNA binding by FliZ. However, while a number of FliZ binding sites correspond to known sigma(S)-dependent promoters, promoter activity is not a prerequisite for FliZ binding and repressor function. Thus, we demonstrate that FliZ also feedback-controls flagellar gene expression by binding to a site in the flhDC control region that shows similarity only to a -10 element of a sigma(S)-dependent promoter, but does not function as a promoter. PMID- 22323520 TI - Summarizing and correcting the GC content bias in high-throughput sequencing. AB - GC content bias describes the dependence between fragment count (read coverage) and GC content found in Illumina sequencing data. This bias can dominate the signal of interest for analyses that focus on measuring fragment abundance within a genome, such as copy number estimation (DNA-seq). The bias is not consistent between samples; and there is no consensus as to the best methods to remove it in a single sample. We analyze regularities in the GC bias patterns, and find a compact description for this unimodal curve family. It is the GC content of the full DNA fragment, not only the sequenced read, that most influences fragment count. This GC effect is unimodal: both GC-rich fragments and AT-rich fragments are underrepresented in the sequencing results. This empirical evidence strengthens the hypothesis that PCR is the most important cause of the GC bias. We propose a model that produces predictions at the base pair level, allowing strand-specific GC-effect correction regardless of the downstream smoothing or binning. These GC modeling considerations can inform other high-throughput sequencing analyses such as ChIP-seq and RNA-seq. PMID- 22323521 TI - Lactate, a product of glycolytic metabolism, inhibits histone deacetylase activity and promotes changes in gene expression. AB - Chemical inhibitors of histone deacetylase (HDAC) activity are used as experimental tools to induce histone hyperacetylation and deregulate gene transcription, but it is not known whether the inhibition of HDACs plays any part in the normal physiological regulation of transcription. Using both in vitro and in vivo assays, we show that lactate, which accumulates when glycolysis exceeds the cell's aerobic metabolic capacity, is an endogenous HDAC inhibitor, deregulating transcription in an HDAC-dependent manner. Lactate is a relatively weak inhibitor (IC(50) 40 mM) compared to the established inhibitors trichostatin A and butyrate, but the genes deregulated overlap significantly with those affected by low concentrations of the more potent inhibitors. HDAC inhibition causes significant up and downregulation of genes, but genes that are associated with HDAC proteins are more likely to be upregulated and less likely to be downregulated than would be expected. Our results suggest that the primary effect of HDAC inhibition by endogenous short-chain fatty acids like lactate is to promote gene expression at genes associated with HDAC proteins. Therefore, we propose that lactate may be an important transcriptional regulator, linking the metabolic state of the cell to gene transcription. PMID- 22323522 TI - A workflow for genome-wide mapping of archaeal transcription factors with ChIP seq. AB - Deciphering the structure of gene regulatory networks across the tree of life remains one of the major challenges in postgenomic biology. We present a novel ChIP-seq workflow for the archaea using the model organism Halobacterium salinarum sp. NRC-1 and demonstrate its application for mapping the genome-wide binding sites of natively expressed transcription factors. This end-to-end pipeline is the first protocol for ChIP-seq in archaea, with methods and tools for each stage from gene tagging to data analysis and biological discovery. Genome-wide binding sites for transcription factors with many binding sites (TfbD) are identified with sensitivity, while retaining specificity in the identification the smaller regulons (bacteriorhodopsin-activator protein). Chromosomal tagging of target proteins with a compact epitope facilitates a standardized and cost-effective workflow that is compatible with high-throughput immunoprecipitation of natively expressed transcription factors. The Pique package, an open-source bioinformatics method, is presented for identification of binding events. Relative to ChIP-Chip and qPCR, this workflow offers a robust catalog of protein-DNA binding events with improved spatial resolution and significantly decreased cost. While this study focuses on the application of ChIP seq in H. salinarum sp. NRC-1, our workflow can also be adapted for use in other archaea and bacteria with basic genetic tools. PMID- 22323523 TI - Novel RNA base pair with higher specificity using single selenium atom. AB - Specificity of nucleobase pairing provides essential foundation for genetic information storage, replication, transcription and translation in all living organisms. However, the wobble base pairs, where U in RNA (or T in DNA) pairs with G instead of A, might compromise the high specificity of the base pairing. The U/G wobble pairing is ubiquitous in RNA, especially in non-coding RNA. In order to increase U/A pairing specificity, we have hypothesized to discriminate against U/G wobble pair by tailoring the steric and electronic effects at the 2 exo position of uridine and replacing the 2-exo oxygen with a selenium atom. We report here the first synthesis of the 2-Se-U-RNAs as well as the 2-Se-uridine ((Se)U) phosphoramidite. Our biophysical and structural studies of the (Se)U-RNAs indicate that this single atom replacement can indeed create a novel U/A base pair with higher specificity than the natural one. We reveal that the (Se)U/A pair maintains a structure virtually identical to the native U/A base pair, while discriminating against U/G wobble pair. This oxygen replacement with selenium offers a unique chemical strategy to enhance the base pairing specificity at the atomic level. PMID- 22323524 TI - A tunable zinc finger-based framework for Boolean logic computation in mammalian cells. AB - The ability to perform molecular-level computation in mammalian cells has the potential to enable a new wave of sophisticated cell-based therapies and diagnostics. To this end, we developed a Boolean logic framework utilizing artificial Cys(2)-His(2) zinc finger transcription factors (ZF-TFs) as computing elements. Artificial ZFs can be designed to specifically bind different DNA sequences and thus comprise a diverse set of components ideal for the construction of scalable networks. We generate ZF-TF activators and repressors and demonstrate a novel, general method to tune ZF-TF response by fusing ZF-TFs to leucine zipper homodimerization domains. We describe 15 transcriptional activators that display 2- to 463-fold induction and 15 transcriptional repressors that show 1.3- to 16-fold repression. Using these ZF-TFs, we compute OR, NOR, AND and NAND logic, employing hybrid promoters and split intein-mediated protein splicing to integrate signals. The split intein strategy is able to fully reconstitute the ZF-TFs, maintaining them as a uniform set of computing elements. Together, these components comprise a robust platform for building mammalian synthetic gene circuits capable of precisely modulating cellular behavior. PMID- 22323525 TI - Accuracy of respiratory rate monitoring using a non-invasive acoustic method after general anaesthesia. AB - BACKGROUND: Respiratory rate should be monitored continuously in the post anaesthesia care unit (PACU) to avoid any delay in the detection of respiratory depression. Capnometry is the standard of care but in extubated patients requires a nasal cannula or a face mask that may be poorly tolerated or can be dislodged, leading to errors in data acquisition and false alarms. The value of a new non invasive acoustic monitor in this setting has not been fully investigated. METHODS: Adult patients admitted to the PACU after general anaesthesia were included. After tracheal extubation, an adhesive sensor with an integrated acoustic transducer (RRaTM) was placed on the patient's throat and connected to its monitor while the patient breathed through a face mask with a carbon dioxide sampling port (CapnomaskTM) connected to a capnometer. Both the acoustic monitor and the capnometer were connected to a computer to record one pair of data per second for up to 60 min. RESULTS: Fifty-two patients, mean (range) age 54 (22-84) yr and BMI 26 (19-39) kg m(-2), were studied. Compared with capnometry, the bias and limits of agreement of the acoustic method were 0 (-1.4-1.4) bpm. The acoustic sensor was well tolerated while the face mask was removed by eight patients, leading to study discontinuation in two patients. CONCLUSIONS: In extubated patients, continuous assessment of respiration rate with an acoustic monitor correlated well with capnometry. PMID- 22323526 TI - Does canopy mean nitrogen concentration explain variation in canopy light use efficiency across 14 contrasting forest sites? AB - The maximum light use efficiency (LUE = gross primary production (GPP)/absorbed photosynthetic photon flux density (aPPFD)) of plant canopies has been reported to vary spatially and some of this variation has previously been attributed to plant species differences. The canopy nitrogen concentration [N] can potentially explain some of this spatial variation. However, the current paradigm of the N effect on photosynthesis is largely based on the relationship between photosynthetic capacity (A(max)) and [N], i.e., the effects of [N] on photosynthesis rates appear under high PPFD. A maximum LUE-[N] relationship, if it existed, would influence photosynthesis in the whole range of PPFD. We estimated maximum LUE for 14 eddy-covariance forest sites, examined its [N] dependency and investigated how the [N]-maximum LUE dependency could be incorporated into a GPP model. In the model, maximum LUE corresponds to LUE under optimal environmental conditions before light saturation takes place (the slope of GPP vs. PPFD under low PPFD). Maximum LUE was higher in deciduous/mixed than in coniferous sites, and correlated significantly with canopy mean [N]. Correlations between maximum LUE and canopy [N] existed regardless of daily PPFD, although we expected the correlation to disappear under low PPFD when LUE was also highest. Despite these correlations, including [N] in the model of GPP only marginally decreased the root mean squared error. Our results suggest that maximum LUE correlates linearly with canopy [N], but that a larger body of data is required before we can include this relationship into a GPP model. Gross primary production will therefore positively correlate with [N] already at low PPFD, and not only at high PPFD as is suggested by the prevailing paradigm of leaf-level A(max)-[N] relationships. This finding has consequences for modelling GPP driven by temporal changes or spatial variation in canopy [N]. PMID- 22323528 TI - Sirolimus protective effects on bone: the need to be demonstrated. PMID- 22323527 TI - Oncolytic immunotherapy of advanced solid tumors with a CD40L-expressing replicating adenovirus: assessment of safety and immunologic responses in patients. AB - The immunosuppressive environment of advanced tumors is a primary obstacle to the efficacy of immunostimulatory and vaccine approaches. Here, we report an approach to arm an oncolytic virus with CD40 ligand (CD40L) to stimulate beneficial immunologic responses in patients. A double-targeted chimeric adenovirus controlled by the hTERT promoter and expressing CD40L (CGTG-401) was constructed and nine patients with progressing advanced solid tumors refractory to standard therapies were treated intratumorally. No serious adverse events resulting in patient hospitalization occurred. Moderate or no increases in neutralizing antibodies were seen, suggesting effective Th1 immunologic effects. An assessment of the blood levels of virus indicated 17.5% of the samples (n = 40) were positive at a low level early after treatment, but not thereafter. In contrast, high levels of virus, CD40L, and RANTES were documented locally at the tumor. Peripheral blood mononuclear cells were analyzed by IFN-gamma ELISPOT analysis and induction of both survivin-specific and adenovirus-specific T cells was seen. Antitumor T-cell responses were even more pronounced when assessed by intracellular cytokine staining after stimulation with tumor type-specific peptide pools. Of the evaluable patients, 83% displayed disease control at 3 months and in both cases in which treatment was continued the effect was sustained for at least 8 months. Injected and noninjected lesions responded identically. Together, these findings support further clinical evaluation of CGTG 401. PMID- 22323529 TI - Vasopressin release is enhanced by the Hemocontrol biofeedback system and could contribute to better haemodynamic stability during haemodialysis. AB - BACKGROUND: Haemodialysis with the Hemocontrol biofeedback system (HHD) is associated with improved haemodynamic stability compared with standard haemodialysis (HD) (SHD). Although the beneficial effect of HHD on haemodynamic stability is generally explained by its effect on blood volume, we questioned whether additional factors could play a role. Since HHD is associated with higher initial dialysate sodium concentrations and ultrafiltration (UF) rate, we studied whether the beneficial effect of HHD on haemodynamic stability may be explained by an increased release of the vasoconstrictor arginine vasopressin (AVP). METHODS: Fifteen chronic dialysis patients underwent SHD and HHD in random order. All other treatment factors were identical and patients served as their own control. Plasma levels of AVP were measured pre-dialysis, at 30 and 60 min intra dialysis and, next, hourly until completion of the dialysis session. RESULTS: Plasma AVP levels did not change significantly during SHD, whereas AVP levels rose significantly within 30 min after the start of HHD (P < 0.01). AVP levels were significantly higher at 30 and 60 min of HHD in comparison with SHD (P < 0.05). Dialysis hypotension occurred significantly less frequent during HHD than during SHD (P < 0.05). CONCLUSIONS: HHD is associated with higher initial AVP levels compared with SHD. The enhanced release of the vasoconstrictor AVP with HHD could contribute to the lower frequency of dialysis hypotension by facilitating fluid removal during the first part of the dialysis session, permitting lower UF rates during the second half of the dialysis session. PMID- 22323530 TI - Genital human papillomavirus infections: current and prospective therapies. AB - Infection with human papillomaviruses (HPVs) is very common and associated with benign and malignant epithelial proliferations of skin and internal squamous mucosae. A subset of the mucosal HPVs are oncogenic and associated with 5 % of all cancers in men and women. There are two licensed prophylactic vaccines, both target HPV 16 and 18, the two most pathogenic, oncogenic types and one, additionally, targets HPV 6 and 11 the cause of genital warts. The approach of deliberate immunization with oncogenic HPV E6 and/or E7 proteins and the generation of antigen-specific cytotoxic T-cells as an immunotherapy for HPV associated cancer and their high-grade pre-cancers has been tested with a wide array of potential vaccine delivery systems in Phase I/II trials with varying success. Understanding local viral and tumour immune evasion strategies is a prerequisite for the rational design of therapeutic vaccines for HPV-associated infection and disease, progress in this is discussed. There are no antiviral drugs for the treatment of HPV infection and disease. Current therapies are not targeted antiviral therapies, but either attempt physical removal of the lesion or induce inflammation and a bystander immune response. There has been recent progress in the identification and characterization of molecular targets for small molecule antagonists of the HPV proteins E1, E2 and E6 or their interactions with their cellular targets. Lead compounds that could disrupt E1-E2 protein-protein interactions have been discovered as have inhibitors of E6-E6-AP binding interactions. Some of these compounds showed nanomolar affinities and high specificities and demonstrate the feasibility of this approach for HPV infections. These studies are, however, at an early phase and it is unlikely that any specific anti-HPV chemotherapeutic will be in the clinic within the next 10 20 years. PMID- 22323531 TI - PrP(Sc) detection and infectivity in semen from scrapie-infected sheep. AB - A scrapie-positive ewe was found in a flock that had been scrapie-free for 13 years, but housed adjacent to scrapie-positive animals, separated by a wire fence. Live animal testing of the entire flock of 24 animals revealed seven more subclinical scrapie-positive ewes. We hypothesized that they may have contracted the disease from scrapie-positive rams used for breeding 4 months prior, possibly through the semen. The genotypes of the ewe flock were highly scrapie-susceptible and the rams were infected with the 'Caine' scrapie strain having a short incubation time of 4.3-14.6 months in sheep with 136/171 VQ/VQ and AQ/VQ genotypes. PrP(Sc) accumulates in a variety of tissues in addition to the central nervous system. Although transmission of prion diseases, or transmissible spongiform encephalopathies, has been achieved via peripheral organ or tissue homogenates as well as by blood transfusion, neither infectivity nor PrP(Sc) have been found in semen from scrapie-infected animals. Using serial protein misfolding cyclic amplification followed by a surround optical fibre immunoassay, we demonstrate that semen from rams infected with a short-incubation-time scrapie strain contains prion disease-associated-seeding activity that generated PrP(Sc) in sPMCA (serial protein misfolding cyclic amplification). Injection of the ovinized transgenic mouse line TgSShpPrP with semen from scrapie-infected sheep resulted in PrP(Sc)-seeding activity in clinical and, probably as a result of the low titre, non-clinical mouse brain. These results suggest that the transmissible agent, or at least the seeding activity, for sheep scrapie is present in semen. This may be a strain-specific phenomenon. PMID- 22323532 TI - An influenza reassortant with polymerase of pH1N1 and NS gene of H3N2 influenza A virus is attenuated in vivo. AB - Influenza viruses readily mutate by accumulating point mutations and also by reassortment in which they acquire whole gene segments from another virus in a co infected host. The NS1 gene is a major virulence factor of influenza A virus. The effects of changes in NS1 sequence depend on the influenza polymerase constellation. Here, we investigated the consequences of a virus with the polymerase of pandemic H1N1 2009 acquiring an NS gene segment derived from a seasonal influenza A H3N2 virus, a combination that might arise during natural reassortment of viruses that currently circulate in humans. We generated recombinant influenza viruses with surface HA and NA genes and matrix M gene segment from A/PR/8/34 virus, but different combinations of polymerase and NS genes. Thus, any changes in phenotype were not due to differences in receptor use, entry, uncoating or virus release. In Madin-Darby canine kidney (MDCK) cells, the virus with the NS gene from the H3N2 parent showed enhanced replication, probably a result of increased control of the interferon response. However, in mice the same virus was attenuated in comparison with the virus containing homologous pH1N1 polymerase and NS genes. Levels of viral RNA during single-cycles of replication were lower for the virus with H3N2 NS, and this virus reached lower titres in the lungs of infected mice. Thus, virus with pH1N1 polymerase genes did not increase its virulence by acquiring the H3N2 NS gene segment, and MDCK cells were a poor predictor of the outcome of infection in vivo. PMID- 22323533 TI - Fewer pre-emptive renal transplantations and more rejections in immigrant children compared to native Dutch and Belgian children. AB - BACKGROUND: In the Netherlands and Belgium, an increasing number of children who have end-stage renal disease (ESRD) are of non-Western origin. We analysed renal transplantation practices and outcome for immigrant ESRD children as compared to native children in both countries. METHODS: All Dutch and Belgian children aged <19 years who received their first renal transplantation between 1 September 2007 and 1 January 2011 were included. Therapy characteristics and outcomes were registered prospectively on a 3-monthly basis. Immigrants were defined as children of whom one or both parents had been born outside Western European countries. Multivariable Cox regression analysis was used to quantify the hazard ratio for acute rejection. RESULTS: One hundred and nineteen first renal transplant recipients were included, of which 41 (34%) were immigrants. Median [range] follow-up time of transplantation was 18 [2-28] months. Compared to native children, immigrants had pre-emptive transplantations (15 versus 32%, P = 0.040) and transplantations with a kidney from a living donor less often (24 versus 59%, P < 0.001). Survival analysis in 96 children with at least 3 months of follow-up showed an increased risk for acute rejection in immigrants adjusted for donor source, duration of dialysis and number of HLA mismatches on the DR locus [hazard ratio (95% confidence interval) 2.5 (1.1-5.9)]. CONCLUSIONS: Immigrant children receive fewer pre-emptive and living donor transplantations compared to native children. After transplantation, immigrant children are at higher risk for acute rejection irrespective of the mode of transplantation. PMID- 22323534 TI - Endogenous cardioprotection by ischaemic postconditioning and remote conditioning. AB - Persistent myocardial ischaemia causes cell death if not rescued by early reperfusion. Millions of years in nature's laboratory have evolved protective responses that 'condition' the heart (and other tissues) to adapt to stressors, and these responses are applicable to the relatively new societal stress of myocardial ischaemia and reperfusion injury. Conditioning can be applied before (preconditioning), during (perconditioning), or after (postconditioning) the ischaemic stressor by imposing short periods of non-lethal ischaemia separated by brief periods of reperfusion. This conditioning protects multiple cell types and induces or rebalances a number of physiological and molecular pathways that ultimately attenuate necrosis and apoptosis. The seemingly disparate pathways may converge directly or indirectly on the mitochondria as a final effector, but other pathways not affecting mitochondria broaden the mechanisms of cardioprotection. The potential downsides of imposing even brief ischaemia directly on the heart somewhat tempered the enthusiasm for applying conditioning stimuli to the heart, but this hurdle was surmounted by applying ischaemia to remote organs and tissues in pre-, per-, and postconditioning. Although the clinical translation of remote per- and postconditioning has been rapid compared with classical preconditioning, there are numerous basic questions that require further investigation, and wider adoption awaits large-scale randomized clinical trials. Pharmacological mimetics may provide another important therapeutic approach by which to treat evolving myocardial infarction. PMID- 22323535 TI - The adaptor protein SLP-76 regulates HIV-1 release and cell-to-cell transmission in T cells. AB - HIV-1 infection in T cells is regulated by TCR activation. However, the cellular proteins of the TCR pathway that regulate HIV-1 infection are poorly characterized. In this study, in HIV-1 infection, we observed a significant reduction of HIV-1 virus production in Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76)-deficient Jurkat T cells compared with wild-type and SLP-76-reconstituted Jurkat T cells. We further confirmed the role of SLP-76 in HIV-1 infection by small interfering RNA-mediated knockdown in MT4 cells and PBMCs. Structural-functional analysis revealed that the N-terminal domain of SLP 76 was important for regulating HIV-1 infection. Further mechanistic studies revealed that lack of SLP-76 impaired virus release, but did not affect viral entry, integration, and transcription. We also showed that SLP-76 plays a critical role in cell-to-cell transmission of HIV-1. Signaling studies revealed that SLP-76 associated with viral negative regulatory factor protein and multiple signaling molecules during HIV-1 infection. Furthermore, SLP-76 facilitated the association of negative regulatory factor and F-actin, suggesting that SLP-76 mediates the formation of a signaling complex that may regulate viral release via cytoskeletal changes. Taken together, our studies demonstrate a novel role for the adaptor molecule SLP-76 in regulating HIV-1 infection in T cells with the potential to develop innovative strategies against HIV-1. PMID- 22323536 TI - E3 ubiquitin ligase tripartite motif 38 negatively regulates TLR-mediated immune responses by proteasomal degradation of TNF receptor-associated factor 6 in macrophages. AB - Activation of TLR signaling in the innate immune cells is critical for the elimination of invading microorganisms. However, uncontrolled activation may lead to autoimmune and inflammatory diseases. In this article, we report the identification of tripartite motif (TRIM) 38 as a negative feedback regulator in TLR signaling by targeting TNFR-associated factor 6 (TRAF6). TRIM38 was induced by TLR stimulation in an NF-kappaB-dependent manner in macrophages. Knockdown of TRIM38 expression by small interfering RNA resulted in augmented activation of NF kappaB and MAPKs, and enhanced expression of proinflammatory cytokines, whereas overexpression of TRIM38 has an opposite effect. As an E3 ligase, TRIM38 bound to TRAF6 and promoted K48-linked polyubiquitination, which led to the proteasomal degradation of TRAF6. Consistently, knockdown of TRIM38 expression resulted in higher protein level of TRAF6 in primary macrophages. Our findings defined a novel function for TRIM38 to prevent excessive TLR-induced inflammatory responses through proteasomal degradation of TRAF6. PMID- 22323537 TI - Cutting edge: the "death" adaptor CRADD/RAIDD targets BCL10 and suppresses agonist-induced cytokine expression in T lymphocytes. AB - The expression of proinflammatory cytokines and chemokines in response to TCR agonists is regulated by the caspase-recruitment domain membrane-associated guanylate kinase 1 (CARMA1) signalosome through the coordinated assembly of complexes containing the BCL10 adaptor protein. We describe a novel mechanism to negatively regulate the CARMA1 signalosome by the "death" adaptor protein caspase and receptor interacting protein adaptor with death domain (CRADD)/receptor interacting protein-associated ICH-1/CED-3 homologous protein with a death domain. We show that CRADD interacts with BCL10 through its caspase recruitment domain and suppresses interactions between BCL10 and CARMA1. TCR agonist-induced interaction between CRADD and BCL10 coincides with reduction of its complex formation with CARMA1 in wild-type, as compared with Cradd-deficient, primary cells. Finally, Cradd-deficient spleen cells, CD4(+) T cells, and mice respond to T cell agonists with strikingly higher production of proinflammatory mediators, including IFN-gamma, IL-2, TNF-alpha, and IL-17. These results define a novel role for CRADD as a negative regulator of the CARMA1 signalosome and suppressor of Th1- and Th17-mediated inflammatory responses. PMID- 22323538 TI - Analysis of NLRP3 in the development of allergic airway disease in mice. AB - The contribution of NLRP3, a member of the nucleotide-binding domain leucine-rich repeat-containing (NLR) family, to the development of allergic airway disease is currently controversial. In this study, we used multiple allergic asthma models to examine the physiologic role of NLRP3. We found no significant differences in airway eosinophilia, histopathologic condition, mucus production, and airway hyperresponsiveness between wild-type and Nlrp3(-/-) mice in either acute (alum dependent) or chronic (alum-independent) OVA models. In addition to the OVA model, we did not detect a role for NLRP3 in the development of allergic airway disease induced by either acute or chronic house dust mite Ag exposure. Although we did not observe significant phenotypic differences in any of the models tested, we did note a significant reduction of IL-13 and IL-33 in Nlrp3(-/-) mice compared with wild-type controls in the chronic OVA model without added alum. In all of the allergic airway disease models, the NLRP3 inflammasome-associated cytokines IL-1beta and IL-18 in the lung were below the level of detection. In sum, this report surveyed four different allergic asthma models and found a modest and selected role for NLRP3 in the alum-free OVA model. However, this difference did not greatly alter the clinical outcome of the disease. This finding suggests that the role of NLRP3 in allergic asthma must be re-evaluated. PMID- 22323539 TI - The impact of a large and frequent deletion in the human TCR beta locus on antiviral immunity. AB - The TCR plays a critical role in recognizing intracellular pathogens and initiating pathways leading to the destruction of infected cells by the immune system. Although genetic variability is known to greatly impact on the human immune system and the outcome of infection, the influence of sequence variation leading to the inactivation or deletion of TCR gene segments is unknown. To investigate this issue, we examined the CD8(+) T cell response to an HLA-B7 restricted epitope ((265)RPHERNGFTVL(275)) from the pp65 Ag of human CMV that was highly biased and frequently dominated by a public TCR beta-chain encoded by the variable gene segment TRBV4-3. Approximately 40% of humans lack T cells expressing TRBV4-3 because of a 21.5-kb insertion/deletion polymorphism, but these individuals remain responsive to this epitope, using a diverse T cell repertoire characterized by private TCR usage. Although most residues within the bulged 11-mer peptide were accessible for TCR contact, the public and private TCRs showed distinct patterns of sensitivity to amino acid substitution at different positions within the peptide, thereby suggesting that the repertoire diversity generated in the absence of the dominant public TRBV4-3(+) TCR could lead to better protection from viral escape mutation. Thus, variation in the size of the TRBV repertoire clearly contributes toward interindividual variability in immune responses and is presumably maintained in many ethnic groups to enhance the diversity of Ag-specific T cell responses. PMID- 22323540 TI - Midkine inhibits inducible regulatory T cell differentiation by suppressing the development of tolerogenic dendritic cells. AB - Midkine (MK), a heparin-binding growth factor, reportedly contributes to inflammatory diseases, including Crohn's disease and rheumatoid arthritis. We previously showed that MK aggravates experimental autoimmune encephalomyelitis (EAE) by decreasing regulatory CD4(+)CD25(+)Foxp3(+) T cells (Tregs), a population that regulates the development of autoimmune responses, although the precise mechanism remains uncertain. In this article, we show that MK produced in inflammatory conditions suppresses the development of tolerogenic dendritic cells (DCregs), which drive the development of inducible Treg. MK suppressed DCreg mediated expansion of the CD4(+)CD25(+)Foxp3(+) Treg population. DCregs expressed significantly higher levels of CD45RB and produced significantly less IL-12 compared with conventional dendritic cells. However, MK downregulated CD45RB expression and induced IL-12 production by reducing phosphorylated STAT3 levels via src homology region 2 domain-containing phosphatase-2 in DCreg. Inhibiting MK activity with anti-MK RNA aptamers, which bind to the targeted protein to suppress the function of the protein, increased the numbers of CD11c(low)CD45RB(+) dendritic cells and Tregs in the draining lymph nodes and suppressed the severity of EAE, an animal model of multiple sclerosis. Our results also demonstrated that MK was produced by inflammatory cells, in particular, CD4(+) T cells under inflammatory conditions. Taken together, these results suggest that MK aggravates EAE by suppressing DCreg development, thereby impairing the Treg population. Thus, MK is a promising therapeutic target for various autoimmune diseases. PMID- 22323541 TI - Stromal TIMP3 regulates liver lymphocyte populations and provides protection against Th1 T cell-driven autoimmune hepatitis. AB - Lymphocyte infiltration into epithelial tissues and proinflammatory cytokine release are key steps in autoimmune disease. Although cell-autonomous roles of lymphocytes are well studied in autoimmunity, much less is understood about the stromal factors that dictate immune cell function. Tissue inhibitor of metalloproteinases 3 (TIMP3) controls systemic cytokine bioavailability and signaling by inhibiting the ectodomain shedding of cytokines and their receptors. The role of TIMP3 in cytokine biology is emerging; however, its contribution to cellular immunology remains unknown. In this study, we show that TIMP3 produced by the hepatic stroma regulates the basal lymphocyte populations in the liver and prevents autoimmune hepatitis. TIMP3 deficiency in mice led to spontaneous accumulation and activation of hepatic CD4(+), CD8(+), and NKT cells. Treatment with Con A in a model of polyclonal T lymphocyte activation resulted in a greatly enhanced Th1 cytokine response and acute liver failure, which mechanistically depended on TNF signaling. Bone marrow chimeras demonstrated that TIMP3 derived from the stromal rather than hematopoietic compartment provided protection against autoimmunity. Finally, we identified hepatocytes as the major source of Timp3 in a resting liver, whereas significant Timp3 gene transcription was induced by hepatic stellate cells in the inflamed liver. These results uncover metalloproteinase inhibitors as critical stromal factors in regulating cellular immunity during autoimmune hepatitis. PMID- 22323542 TI - A new hypersensitive site, HS10, and the enhancers, E3' and Ed, differentially regulate Igkappa gene expression. AB - The mouse Igkappa gene locus has three known transcriptional enhancers: an intronic enhancer (Ei), a 3' enhancer (E3'), and a further downstream enhancer (Ed). We previously discovered, using the chromosome conformation-capture technique, that Ei and E3' interact with a novel DNA sequence near the 3' end of the Igkappa locus, specifically in B cells. In the present investigation, we examined the function of this far downstream element. The sequence is evolutionarily conserved and exhibits a plasmacytoma cell-specific DNase I hypersensitive site in chromatin, henceforth termed HS10 in the locus. HS10 acts as a coactivator of E3' in transient transfection assays. Although HS10(-/-) mice exhibited normal patterns of B cell development, they were tested further along with E3'(-/-) and Ed(-/-) mice for their Igkappa expression levels in plasma cells, as well as for both allelic and isotype exclusion in splenic B cells. HS10(-/-) and Ed(-/-), but not E3'(-/-), mice exhibited 2.5-fold lower levels of Igkappa expression in antigenically challenged plasma cells. E3'(-/-) mice, but not HS10(-/-) mice, exhibited impaired IgL isotype and allelic exclusion in splenic B cells. We have suggestive results that Ed may also weakly participate in these processes. In addition, HS10(-/-) mice no longer exhibited regional chromosome interactions with E3', and they exhibited modestly reduced somatic hypermutation in the Jkappa-Ckappa intronic region in germinal center B cells from Peyer's patches. We conclude that the HS10, E3', and Ed differentially regulate Igkappa gene dynamics. PMID- 22323543 TI - Germinal center alloantibody responses are mediated exclusively by indirect pathway CD4 T follicular helper cells. AB - The durable alloantibody responses that develop in organ transplant patients indicate long-lived plasma cell output from T-dependent germinal centers (GCs), but which of the two pathways of CD4 T cell allorecognition is responsible for generating allospecific T follicular helper cells remains unclear. This was addressed by reconstituting T cell-deficient mice with monoclonal populations of TCR-transgenic CD4 T cells that recognized alloantigen only as conformationally intact protein (direct pathway) or only as self-restricted allopeptide (indirect pathway) and then assessing the alloantibody response to a heart graft. Recipients reconstituted with indirect-pathway CD4 T cells developed long-lasting IgG alloantibody responses, with splenic GCs and allospecific bone marrow plasma cells readily detectable 50 d after heart transplantation. Differentiation of the transferred CD4 T cells into T follicular helper cells was confirmed by follicular localization and by acquisition of signature phenotype. In contrast, IgG alloantibody was not detectable in recipient mice reconstituted with direct pathway CD4 T cells. Neither prolongation of the response by preventing NK cell killing of donor dendritic cells nor prior immunization to develop CD4 T cell memory altered the inability of the direct pathway to provide allospecific B cell help. CD4 T cell help for GC alloantibody responses is provided exclusively via the indirect-allorecognition pathway. PMID- 22323544 TI - Downregulation of the Na/K-ATPase pump by leptospiral glycolipoprotein activates the NLRP3 inflammasome. AB - Leptospira interrogans is responsible for a zoonotic disease known to induce severe kidney dysfunction and inflammation. In this work, we demonstrate that L. interrogans induces NLRP3 inflammasome-dependent secretion of IL-1beta through the alteration of potassium transport in bone marrow-derived macrophages. Lysosome destabilization also contributed to the IL-1beta production upon stimulation with live, but not dead, bacteria. Using bone marrow-derived macrophages from various TLRs and nucleotide-binding oligomerization domain deficient mice, we further determined that IL-1beta production was dependent on TLR2 and TLR4, suggesting a participation of the leptospiral LPS to this process. Hypokaliemia in leptospirosis has been linked to the presence of glycolipoprotein, a cell wall component of L. interrogans that is known to inhibit the expression and functions of the Na/K-ATPase pump. We show in this study that glycolipoprotein activates the inflammasome and synergizes with leptospiral LPS to produce IL-1beta, mimicking the effect of whole bacteria. These results were confirmed in vivo, as wild-type mice expressed more IL-1beta in the kidney than TLR2/4-deficient mice 3 d postinfection with L. interrogans. Collectively, these findings provide the first characterization, to our knowledge, of bacteria-induced activation of the NLRP3 inflammasome through the downregulation of a specific host potassium transporter. PMID- 22323545 TI - A TRIF-independent branch of TLR3 signaling. AB - dsRNA is a common pathogen-associated molecular pattern that is recognized by cellular TLR3 and used by virus-infected cells to activate specific transcription factors and trigger induction of antiviral genes. In this article, we report a new branch of TLR3 signaling that does not lead to gene induction but affects many cellular properties, such as cell migration, adhesion, and proliferation. We demonstrated that the migration of multiple cell lineages was affected by dsRNA treatment or influenza virus infection in a TLR3-dependent fashion. Surprisingly, for this effect of TLR3 signaling, the adaptor proteins, TRIF and MyD88, were not required. The effects of the new pathway were mediated by the proto-oncoprotein c Src, which bound to TLR3 after dsRNA stimulation of cells. The response was biphasic: upon dsRNA treatment, we observed an immediate increase in cell motility followed by its strong inhibition. Our results indicate that the first phase was mediated by dsRNA-induced phosphorylation and activation of Src, whereas the second phase resulted from the sequestration of activated Src in lipid rafts, thus decreasing its active cytoplasmic pool. As expected, two other functions of Src, its effect on cell adhesion and cell proliferation, were also inhibited by dsRNA treatment. These results demonstrate that activated TLR3 can engage Src to trigger multiple cellular effects and reveal a possible link between innate immune response and cell growth regulation. This study also provides a rare example of TLR-mediated cellular effects that do not require gene induction and the first example, to our knowledge, of an adaptor-independent effect of any TLR. PMID- 22323546 TI - Targeting TNF-alpha to neoangiogenic vessels enhances lymphocyte infiltration in tumors and increases the therapeutic potential of immunotherapy. AB - Abnormal tumor vasculature impairs T lymphocyte adhesion to endothelial cells and lymphocyte extravasation into neoplastic tissues, limiting the therapeutic potential of both active and adoptive immunotherapies. We have found that treatment of tumor-bearing mice with NGR-TNF, a Cys-Asn-Gly-Arg-Cys peptide-TNF fusion product capable of altering the endothelial barrier function and improving drug penetration in tumors, associated with the intratumor upregulation of leukocyte-endothelial cell adhesion molecules, the release of proinflammatory cytokines and chemokines, and the infiltration of tumor-specific effector CD8(+) T cells. As a result, NGR-TNF enhanced the therapeutic activity of adoptive and active immunotherapy, delaying tumor growth and prolonging survival. Furthermore, we have found that therapeutic effects of these combinations can be further increased by the addition of chemotherapy. Thus, these findings might be relevant for the design of novel immunotherapeutic approaches for cancer patients. PMID- 22323547 TI - PET-diagnosed lead infection in ARVC. PMID- 22323548 TI - Transthoracic echocardiographic guidance of minimally invasive perventricular device closure of perimembranous ventricular septal defect without cardiopulmonary bypass: initial experience. AB - BACKGROUND: Our purpose was to investigate the feasibility of transthoracic echocardiographic (TTE) guidance for minimally invasive periventricular device closure of perimembranous ventricular septal defects (VSDs). METHODS: From June 2011 to September 2011, we enrolled 18 young children with perimembranous VSDs to receive minimally invasive device closure in our hospital. All of the patients were examined by TTE to determine the VSD morphology, diameter, and rims. During intra-operative device closure, real-time bedside TTE alone was used to guide device implantation. RESULTS: Device implantation using TTE guidance was successful in 16 patients. Symmetric devices were used in 14 patients, and asymmetric devices were used in 2 patients. Only one patient experienced mild aortic regurgitation, and there were no instances of residual shunt, significant arrhythmias, thromboembolism, or device displacement. Two patients were transferred to surgical closure, one due to residual shunting and the other as a result of unsuccessful wire penetration of the VSD gap. CONCLUSIONS: Our data indicate that TTE-guided VSD closure is feasible in young children, although a longer follow-up may be needed to document the long-term success. PMID- 22323549 TI - Tissue Doppler echocardiography improves the diagnosis of coronary artery stenosis in stable angina pectoris. AB - Aim To determine if colour tissue Doppler imaging (TDI) performed at rest in patients with suspected stable angina pectoris (SAP) is able to predict the presence of significant coronary artery disease (CAD). METHODS AND RESULTS: This study comprises 296 consecutive patients with clinically suspected SAP, no previous cardiac history, and a normal ejection fraction. All patients were examined by colour TDI, exercise electrocardiogram (ECG), and coronary angiography (CAG). Regional longitudinal systolic (s'), early diastolic (e'), and late diastolic (a') myocardial velocities were measured by colour TDI at six mitral annular sites and averaged to provide global estimates. Duke score (DS), including ST depression, chest pain, and exercise capacity, was used as the outcome of the exercise ECG. Patients with an area stenosis of >=70% in at least one epicardial coronary artery were categorized as having a significant CAD (n= 108) and were compared with patients without significant CAD (n= 188). Both e' [odds ratio (OR): 1.5 (1.1-1.9, P < 0.01) per cm/s decrease] and s' [OR: 1.7 (1.1 2.5, P < 0.05) per cm/s decrease] remained independent predictors of CAD after multivariable adjustment for baseline, exercise ECG, and conventional echocardiographic parameters. Area under the receiver operating characteristic curve (AUC) for exercise ECG and TDI in combination was significantly higher than AUC for exercise ECG alone (0.84 vs. 0.79, P < 0.01). CONCLUSION: In patients with suspected SAP colour TDI performed at rest is an independent predictor of significant CAD, and colour TDI improves the diagnostic performance of exercise ECG. PMID- 22323550 TI - Ras inhibition by FTS attenuates brain tumor growth in mice by direct antitumor activity and enhanced reactivity of cytotoxic lymphocytes. AB - A major concern in targeted drug therapy is that the inhibition of receptors and signaling molecules in tumor cells may also affect similar components in the tumor microenvironment or in the immune system, with undefined consequences for inhibition of tumor growth. One example is given by the Ras inhibitor salirasib (Farnesythiosalycilic acid, FTS), which in addition to its antitumor activity in mice and humans also exhibits anti-inflammatory activity. Here we show three major effects through which Ras inhibition by FTS provides a favorable antitumor environment in immune-competent mice with subcutaneous or intracranial tumors. First, FTS exhibited antitumor activity in intracranial immune-competent tumor bearing mice and increased their survival relative to tumor-bearing immune compromised mice. Second, FTS induced an increase in regulatory T cells in mouse splenocytes, in which Foxp3+ T cells did not interfere with the tumor growth inhibitory effects of FTS. Third, FTS induced an increase in antitumor cytotoxic T-cell reactivity in glioma cells by downregulating their own expression of Foxp3. This downregulation induced a TGF-beta-associated mechanism in glioma cells altering the tumor microenvironment and causing reduced resistance of the tumor to the immune system. These results are important as they might explain some of the major beneficial effects of Ras inhibitors. They may provide an experimental framework for examination of the impact of other anticancer drugs on cancer and the immune system. PMID- 22323551 TI - Re-irradiation for metastatic brain tumors with whole-brain radiotherapy. AB - OBJECTIVE: To determine whether second whole-brain irradiation is beneficial for patients previously treated with whole-brain irradiation. METHODS: A retrospective analysis was done for 31 patients with brain metastases who had undergone re-irradiation. Initial whole-brain irradiation was performed with 30 Gy/10 fractions for 87% of these patients. Whole-brain re-irradiation was performed with 30 Gy/10 fractions for 42% of these patients (3-40 Gy/1-20 fractions). Three patients underwent a third whole-brain irradiation. RESULTS: The median interval between the initial irradiation and re-irradiation was 10 months (range: 2-69 months). The median survival time after re-irradiation was 4 months (range: 1-21 months). The symptomatic improvement rate after re irradiation was 68%, and the partial and complete tumor response rate was 55%. Fifty-two percent of the patients developed Grade 1 acute reactions. On magnetic resonance imaging, brain atrophy was observed in 36% of these patients after the initial irradiation and 74% after re-irradiation. Grade >=2 encephalopathy or cognitive disturbance was observed in 10 patients (32%) after re-irradiation. Based on univariate analysis, significant factors related to survival after re irradiation were the location of the primary cancer (P = 0.003) and the Karnofsky performance status at the time of re-irradiation (P = 0.008). A Karnofsky performance status >=70 was significant based on multivariate analysis (P = 0.050). CONCLUSIONS: Whole-brain re-irradiation for brain metastases placed only a slight burden on patients and was effective for symptomatic improvement. However, their remaining survival time was limited and the incidence of cognitive disturbance was rather high. PMID- 22323552 TI - High expression of microRNA-210 is an independent factor indicating a poor prognosis in Japanese triple-negative breast cancer patients. AB - OBJECTIVE: MicroRNAs have emerged as a new class of non-coding genes involved in regulating cell proliferation, differentiation and viability. Recent studies have identified miR-210 as one of a set of hypoxia-regulated microRNAs and demonstrated a direct regulatory role of HIF-1 alpha for its transcription. Here, we assessed miR-210 expression in Japanese triple-negative breast cancers and determined its clinical significance. METHODS: TaqMan MicroRNA assays for miR-210 expression were performed on 161 samples of Japanese breast cancer tissue (58 triple-negative breast cancer and 103 estrogen receptor positive/HER2 negative). Correlations between miR-210 expression and clinicopathological factors were analyzed. The effects of several variables on survival were tested by a Cox proportional hazards regression analysis. RESULTS: miR-210 expression in triple negative breast cancers was significantly higher than in estrogen receptor positive/HER2-negative breast cancers (P < 0.001). Patients whose triple-negative breast cancers showed low miR-210 expression experienced significantly better disease-free and overall survival than those with high miR-210 expression (P = 0.02 and P = 0.05, respectively). Although the prognosis of patients with triple negative breast cancers is poor, Cox univariate and multivariate analyses demonstrated that a higher expression of miR-210 was an independent factor indicating a worse prognosis than for patients with a low level of miR-210. CONCLUSIONS: The degree of miR-210 expression might be a clinically useful prognostic factor for decision-making regarding treatment in the adjuvant setting, especially in node-negative triple-negative breast cancer patients. PMID- 22323553 TI - Phase II study of oral etoposide and intravenous irinotecan for patients with platinum-resistant and taxane-pretreated ovarian cancer: Japan Clinical Oncology Group Study 0503. AB - A single-arm Phase II study evaluating combination chemotherapy utilizing oral etoposide and irinotecan for platinum-resistant and taxane-pretreated ovarian cancer has started. The aim of this study is to evaluate the efficacy and safety of this regimen as a test arm regimen in a subsequent Phase III trial. Patients with platinum-resistant and taxane-pretreated ovarian cancer are given etoposide at 50 mg/m(2) p.o. from days 1 to 21 and irinotecan 70 mg/m(2) i.v. at days 1 and 15, repeated every 28 days, up to six cycles. A total of 60 patients will be enrolled at 36 institutions. The primary endpoint is response rate. The secondary endpoints include adverse events and progression-free and overall survival. PMID- 22323554 TI - Impact of sunitinib treatment on blood glucose levels in patients with metastatic renal cell carcinoma. AB - OBJECTIVE: To investigate the effects of sunitinib treatment on blood glucose levels in patients with metastatic renal cell carcinoma. METHODS: We reviewed the records of 48 patients who received sunitinib treatment for metastatic renal cell carcinoma between April 2007 and December 2010 at our institution. Patients' data including diabetic status, diabetes mellitus medication and mean blood glucose levels before, during and after the treatment with sunitinib were assessed. RESULTS: In 10 of the 48 (20.8%) patients who were diabetic, the blood glucose level was observed to be significantly decreased after 4 weeks of sunitinib treatment with the mean decrease in blood glucose level being 76.1 +/- 29.0 mg/dl (P = 0.002). Subsequently, after a 2-week off-treatment period, the mean blood glucose level rebound and increased (21.9 +/- 6.3 mg/dl, P = 0.038) in these 10 patients. With sunitinib treatment, one patient was able to discontinue diabetes mellitus medication completely during a 4-week treatment period, and three other patients had dosages of their oral diabetes mellitus medication reduced. Among 38 non-diabetic patients, no significant changes in blood glucose levels were observed during both the 4-week sunitinib treatment period and the 2-week off treatment period. No severe hypoglycemic episode was observed among our subjects. CONCLUSIONS: Sunitinib treatment in diabetic patients with metastatic renal cell carcinoma may result in significantly decreased blood glucose levels. Thus, blood glucose levels should be checked more vigilantly in diabetic patients undergoing sunitinib treatment to adjust diabetes mellitus medications as needed. Further investigation via a larger scaled, prospective study would be needed. PMID- 22323555 TI - Recent progress in carcinogenesis, progression and management of upper GI cancer: the 21st Hiroshima Cancer Seminar--the 5th Three Universities' Consortium International Symposium, 6 November 2011, International Conference Center Hiroshima. AB - The 21st Hiroshima Cancer Seminar focused on recent progress of carcinogenesis, progression and management of upper gastrointestinal cancers. beta-Catenin and p120 mediate peroxisome proliferator-activated receptor delta-dependent proliferation induced by Helicobacter pylori in gastric epithelia. Helicobacter pylori CagA plays an important role in stomach carcinogenesis via altered signal transduction and cell polarity by interactions with several host proteins. Inflammation caused by H. pylori infection is responsible for inducing aberrant DNA methylation. The gastric gland mucin-specific alphaGlcNAc plays dual roles in preventing gastric cancer, inhibition of H. pylori infection and suppression of tumor-promoting inflammation. Information obtained from transcriptome dissection greatly contributes to understanding the molecular character of each mucin phenotype of gastric cancer. The standardized biomarkers will serve as good predictive and prognostic markers for gastric cancer. A microRNA expression profile may be useful for the diagnosis of gastric cancer. Bone marrow-derived mesenchymal stem cells may provide an advantageous microenvironment for re acquisition of stemness of gastric cancer cells. Recent progress in molecular biology research has enabled the clinical development of molecular targeting agents for gastric cancer, such as trastuzumab. The target molecule-based inhibition of the stromal reaction in the microenvironment may hold promise as an effective anti-tumor therapy. Since robotic surgery is feasible and safe, and provides adequate and precise lymph node dissection, it may be one of the good options for gastric cancer in the near future. PMID- 22323556 TI - Killed but metabolically active Leishmania infantum as a novel whole-cell vaccine for visceral leishmaniasis. AB - There are currently no effective vaccines for visceral leishmaniasis, the second most deadly parasitic infection in the world. Here, we describe a novel whole cell vaccine approach using Leishmania infantum chagasi promastigotes treated with the psoralen compound amotosalen (S-59) and low doses of UV A radiation. This treatment generates permanent, covalent DNA cross-links within parasites and results in Leishmania organisms termed killed but metabolically active (KBMA). In this report, we characterize the in vitro growth characteristics of both KBMA L. major and KBMA L. infantum chagasi. Concentrations of S-59 that generate optimally attenuated parasites were identified. Like live L. infantum chagasi, KBMA L. infantum chagasi parasites were able to initially enter liver cells in vivo after intravenous infection. However, whereas live L. infantum chagasi infection leads to hepatosplenomegaly in mice after 6 months, KBMA L. infantum chagasi parasites were undetectable in the organs of mice at this time point. In vitro, KBMA L. infantum chagasi retained the ability to enter macrophages and induce nitric oxide production. These characteristics of KBMA L. infantum chagasi correlated with the ability to prophylactically protect mice via subcutaneous vaccination at levels similar to vaccination with live, virulent organisms. Splenocytes from mice vaccinated with either live L. infantum chagasi or KBMA L. infantum chagasi displayed similar cytokine patterns in vitro. These results suggest that KBMA technology is a potentially safe and effective novel vaccine strategy against the intracellular protozoan L. infantum chagasi. This approach may represent a new method for whole-cell vaccination against other complex intracellular pathogens. PMID- 22323557 TI - CD4 T cell antigens from Staphylococcus aureus Newman strain identified following immunization with heat-killed bacteria. AB - Staphylococcus aureus is a commensal bacterium associated with the skin and mucosal surfaces of humans and animals that can also cause chronic infection. The emergence of antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA) and strains causing chronic intramammary infections (IMI) in cows results in severe human and livestock infections. Conventional approaches to vaccine development have yielded only a few noneffective vaccines against MRSA or IMI strains, so there is a need for improved vaccine development. CD4 T lymphocytes are required for promoting gamma interferon (IFN-gamma) mediated immunoglobulin isotype switching in B lymphocytes to produce high-affinity IgG antibodies and IFN-gamma-mediated phagocyte activation for an effective resolution of bacterial infection. However, the lack of known CD4 T cell antigens from S. aureus has made it difficult to design effective vaccines. The goal of this study was to identify S. aureus proteins recognized by immune CD4 T cells. Using a reverse genetics approach, 43 antigens were selected from the S. aureus Newman strain. These included lipoproteins, proteases, transcription regulators, an alkaline shock protein, conserved-domain proteins, hemolysins, fibrinogen-binding protein, staphylokinase, exotoxin, enterotoxin, sortase, and protein A. Screening of expressed proteins for recall T cell responses in outbred, immune calves identified 13 proteins that share over 80% sequence identity among MRSA or IMI strains. These may be useful for inclusion in a broadly protective multiantigen vaccine against MRSA or IMI. PMID- 22323558 TI - Xenoepitope substitution avoids deceptive imprinting and broadens the immune response to foot-and-mouth disease virus. AB - Many RNA viruses encode error-prone polymerases which introduce mutations into B and T cell epitopes, providing a mechanism for immunological escape. When regions of hypervariability are found within immunodominant epitopes with no known function, they are referred to as "decoy epitopes," which often deceptively imprint the host's immune response. In this work, a decoy epitope was identified in the foot-and-mouth disease virus (FMDV) serotype O VP1 G-H loop after multiple sequence alignment of 118 isolates. A series of chimeric cyclic peptides resembling the type O G-H loop were prepared, each bearing a defined "B cell xenoepitope" from another virus in place of the native decoy epitope. These sequences were derived from porcine respiratory and reproductive syndrome virus (PRRSV), from HIV, or from a presumptively tolerogenic sequence from murine albumin and were subsequently used as immunogens in BALB/c mice. Cross-reactive antibody responses against all peptides were compared to a wild-type peptide and ovalbumin (OVA). A broadened antibody response was generated in animals inoculated with the PRRSV chimeric peptide, in which virus binding of serum antibodies was also observed. A B cell epitope mapping experiment did not reveal recognition of any contiguous linear epitopes, raising the possibility that the refocused response was directed to a conformational epitope. Taken together, these results indicate that xenoepitope substitution is a novel method for immune refocusing against decoy epitopes of RNA viruses such as FMDV as part of the rational design of next-generation vaccines. PMID- 22323559 TI - Association of major histocompatibility complex class 1 chain-related gene a dimorphism with type 1 diabetes and latent autoimmune diabetes in adults in the Algerian population. AB - Major histocompatibility complex class I chain-related gene A (MICA-129) dimorphism was investigated in 73 autoimmune diabetes patients (type 1 diabetes and latent autoimmune diabetes in adults) and 75 controls from Algeria. Only MICA 129 Val allele and MICA-129 Val/Val genotype frequencies were higher among patients than in the control group. Statistical analysis of the estimated extended HLA-DR-DQ-MICA haplotypes shown that individual effects of MICA alleles on HLA-DQ2-DR3-MICA-129 Val/Val and HLA-DQ8-DR4-MICA-129 Val/Val haplotypes were significantly higher in patients than in the control groups. These preliminary data might suggest a relevant role of MICA-129 Val/Val single nucleotide polymorphism (weak/weak binders of NKG2D receptor) in the pathogenesis of T1D and LADA. PMID- 22323560 TI - Analysis of multiple Leptospira interrogans serovar Canicola vaccine proteomes and identification of LipL32 as a biomarker for potency. AB - The current batch potency test for Leptospira interrogans serovar Canicola vaccines requires the use of a large number of hamsters and has severe effects (i.e., hepatic and renal failure resulting in death); while this vaccine is effective, a safer, cheaper, more ethical replacement is desired. The aim of this study was to analyze vaccine proteomes and identify target molecules common to all L. interrogans serovar Canicola vaccines which could be used to design an in vitro potency test. Initial analysis of L. interrogans serovar Canicola vaccines (A to E) from different manufacturers, using the Limulus amebocyte lysate assay and silver-stained sodium dodecyl sulfate polyacrylamide gels, indicated that lipopolysaccharide was not present in all vaccines, preventing it from being a suitable target molecule. The protein contents of vaccines A to E were therefore determined by two-dimensional liquid chromatography mass spectrometry ([2D-LC/MS] 221 +/- 31, 9 +/- 8, 34 +/- 4, 21 +/- 5, and 34 +/- 17 proteins [mean +/- 1 standard deviation] found, respectively). The outer membrane protein LipL32 was established to be common to all and to be present at a significantly higher (P <= 0.05) relative spectral abundance in a batch of vaccine which passed the in vivo potency test than in one which had failed. Further analysis using multiple reaction monitoring revealed that the concentration of the N terminus of LipL32 was significantly lower (P <= 0.01) in failed batches (n = 2) of vaccine than in passed batches (n = 2); the concentration of the C terminus between the two batches was approximately the same. An in vitro Leptospira vaccine potency test, based on N-terminal amino acid quantification of LipL32, was subsequently developed. PMID- 22323561 TI - Mitochondrial function and content in pheochromocytoma/paraganglioma of succinate dehydrogenase mutation carriers. AB - To date, the consequences of succinate dehydrogenase (SDH) impairment on overall mitochondrial functions are still obscure. In this study, we evaluated SDH activity and expression and mitochondrial homeostasis in 57 tissue samples of pheochromocytoma (PHEO)/paraganglioma (PGL) obtained from patients genotyped for PHEO/PGL susceptibility genes. The resulted SDH activity and content always decreased in SDH-mutated tumors, in one out of two MAX-mutated patients and in four patients resulted wild type (wt) at genetic screening. All these four wt patients were further screened for large deletions in SDH genes, TMEM127 and MAX and resulted wt but two had somatic SDHD mutations. The RT-PCR in the MAX-mutated sample suggests that the decrease in SDH depends on complex instability and not on a reduced SDHB expression. SDH mutations neither alter citrate synthase (CS) activity nor the content of voltage-dependent anion channel (VDAC) while the expression of the mitochondrial complex IV (cytochrome c oxidase (COX)) was found extremely variable in all (mutated and wt) samples suggesting an impairment of mitochondrial cristae in these tumors. In conclusion, tumors from patients with germ line SDH mutations invariably show decreased enzymatic activity and content, but an SDH impairment may also depend on SDH somatic mutations or, seemingly, on MAX mutations. The impaired SDH activity in the two wt tissues suggests mutations in other still unknown susceptibility genes. Finally, the extreme variability in COX expression levels is yet to be explained and this strongly suggests to evaluate other mitochondrial features to better understand the mitochondrial role in the pathogenesis of these tumors. PMID- 22323562 TI - KCNJ5 mutations in the National Institutes of Health cohort of patients with primary hyperaldosteronism: an infrequent genetic cause of Conn's syndrome. AB - KCNJ5 mutations were recently described in primary hyperaldosteronism (PH or Conn's syndrome). The frequency of these mutations in PH and the way KCNJ5 defects cause disease remain unknown. A total of 53 patients with PH have been seen at the National Institutes of Health over the last 12 years. Their peripheral and tumor DNAs (the latter from 16 that were operated) were screened for KCNJ5 mutations; functional studies on the identified defects were performed after transient transfection. Only two mutations were identified, and both in the tumor DNA only. There were no germline sequencing defects in any of the patients except for known synonymous variants of the KCNJ5 gene. One mutation was the previously described c.G451C alteration; the other was a novel one in the same codon: c.G451A; both lead to the same amino acid substitution (G151R) in the KCNJ5 protein. Functional studies confirmed previous findings that both mutations caused loss of channel selectivity and a positive shift in the reversal potential. In conclusion, the KCNJ5 protein was strongly expressed in the zona glomerulosa of normal adrenal glands but showed variable expression in the aldosterone-producing adenomas with and without mutation. The rate of KCNJ5 mutations among patients with PH and/or their tumors is substantially lower than what was previously reported. The G151R amino acid substitution appears to be the most frequent one so far detected in PH, despite additional nucleotide changes. The mutation causes loss of this potassium channel's selectivity and may assist in the design of new therapies for PH. PMID- 22323563 TI - Formation of carcinogenic chromosomal rearrangements in human thyroid cells after induction of double-strand DNA breaks by restriction endonucleases. AB - Ionizing radiation (IR) exposure increases the risk of thyroid cancer and other cancer types. Chromosomal rearrangements, such as RET/PTC, are characteristic features of radiation-associated thyroid cancer and can be induced by radiation in vitro. IR causes double-strand breaks (DSBs), suggesting that such damage leads to RET/PTC, but the rearrangement mechanism has not been established. To study the mechanism, we explored the possibility of inducing RET/PTC by electroporation of restriction endonucleases (REs) into HTori-3 human thyroid cells. We used five REs, which induced DSB in a dose-dependent manner similar to that seen with IR. Although all but one RE caused DSB in one or more of the three genes involved in RET/PTC, rearrangement was detected only in cells electroporated with either PvuII (25 and 100 U) or StuI (100 and 250 U). The predominant rearrangement type was RET/PTC3, which is characteristic of human thyroid cancer arising early after Chernobyl-related radioactive iodine exposure. Both enzymes that produced RET/PTC had restriction sites only in one of the two fusion partner genes. Moreover, the two enzymes that produced RET/PTC had restriction sites present in clusters, which was not the case for RE that failed to induce RET/PTC. In summary, we establish a model of DSB induction by RE and report for the first time the formation of carcinogenic chromosomal rearrangements, predominantly RET/PTC3, as a result of DSB produced by RE. Our data also raise a possibility that RET/PTC rearrangement can be initiated by a complex DSB that is induced in one of the fusion partner genes. PMID- 22323565 TI - Predictors of serological cure after treatment of early syphilis. PMID- 22323564 TI - Insulin sensitive and resistant obesity in humans: AMPK activity, oxidative stress, and depot-specific changes in gene expression in adipose tissue. AB - We previously reported that adenosine monophosphate-activated protein kinase (AMPK) activity is lower in adipose tissue of morbidly obese individuals who are insulin resistant than in comparably obese people who are insulin sensitive. However, the number of patients and parameters studied were small. Here, we compared abdominal subcutaneous, epiploic, and omental fat from 16 morbidly obese individuals classified as insulin sensitive or insulin resistant based on the homeostatic model assessment of insulin resistance. We confirmed that AMPK activity is diminished in the insulin resistant group. A custom PCR array revealed increases in mRNA levels of a wide variety of genes associated with inflammation and decreases in PGC-1alpha and Nampt in omental fat of the insulin resistant group. In contrast, subcutaneous abdominal fat of the same patients showed increases in PTP-1b, VEGFa, IFNgamma, PAI-1, and NOS-2 not observed in omental fat. Only angiotensinogen and CD4(+) mRNA levels were increased in both depots. Surprisingly, TNFalpha was only increased in epiploic fat, which otherwise showed very few changes. Protein carbonyl levels, a measure of oxidative stress, were increased in all depots. Thus, adipose tissues of markedly obese insulin resistant individuals uniformly show decreased AMPK activity and increased oxidative stress compared with insulin sensitive patients. However, most changes in gene expression appear to be depot-specific. PMID- 22323567 TI - Viremia and HIV-1 drug resistance mutations among patients receiving second-line highly active antiretroviral therapy in Chennai, Southern India. AB - BACKGROUND: A cross-sectional study among individuals receiving second-line antiretroviral treatment was conducted to report on the level of detectable viremia and the types of drug resistance mutations among those with detectable human immunodeficiency virus (HIV) type 1 plasma viral loads (PVLs). METHODS: PVLs were measured using Abbott m2000rt real-time polymerase chain reaction, and genotyping was performed with the ViroSeq genotyping system, version 2.0, and ViroSeq analysis software, version 2.8. RESULTS: Of 107 patient plasma specimens consecutively analyzed, 30 (28%) had undetectable PVLs (<150 copies/mL), and 77 (72%) were viremic with a median PVL of 5450 copies/mL (interquartile range, 169 1 997 967). Sequencing was done for 107 samples with PVLs >2000 copies/mL: 33 patients (73%) had 1 of the protease (PR) inhibitor mutations; 41 (91%) had nucleoside reverse-transcriptase inhibitor (NRTI) mutations; 33 (73%) had non NRTI (NNRTI) mutations; and 30 (66.7%) had both NRTI and NNRTI mutations. Triple class resistance to NRTIs, NNRTIs, and PR inhibitors was observed in 24 (53%) patients. Based on the mutational profiles observed, all 45 sequences were susceptible to darunavir and tipranavir, whereas 47% showed resistance to lopinavir, 58% showed resistance to atazanavir, and >60% showed resistance to saquinavir, indinavir, nelfinavir, and fosamprenavir. CONCLUSIONS: The results of the study showed that the majority of patients receiving second-line antiretroviral therapy started to accumulate PR resistance mutations, and the mutation profiles suggest that darunavir might be the drug of choice for third line regimens in India. PMID- 22323568 TI - Exposure to second-hand smoke and reproductive outcomes depending on maternal asthma. AB - Tobacco consumption and exposure to second-hand smoke (SHS) are associated with reduced birth weight. One issue that has not been clarified previously is that of the potential higher risk of this outcome in mothers with asthma. We assessed the role of prenatal maternal tobacco use and SHS on reproductive outcomes and assessed the interaction with maternal history of asthma. Data was collected from the INMA study, a maternal birth cohort selected from the general population established in Spain in 2002. We measured cotinine at the 32nd week of pregnancy in 2,219 females. Diagnosed maternal asthma was self-reported during pregnancy. 35% of mothers reported not being exposed to smoking or SHS during pregnancy. Active smoking (i.e. self-reported or cotinine >50 ng.mL(-1)) was related to a 134 g decrease in birth weight and a relative risk of 1.8 for small for gestational age and fetal growth restriction. These results were not modified by maternal asthma. Maternal asthma had a similar frequency in all exposure groups. Non SHS-exposed females had the lowest prevalence of asthma. SHS (i.e. cotinine 20-50 ng.mL(-1)) decreased birth weight by 32 g among those without maternal asthma, but these differences were not statistically significant (95% CI -88.76 24.76). Maternal asthma did not promote these effects. Maternal history of asthma did not modify the effects of smoking on reproductive outcomes in a cohort sampled from the general population. PMID- 22323569 TI - The changing pattern of acute respiratory distress syndrome over time: a comparison of two periods. AB - This study aimed to assess whether patterns and outcomes of acute respiratory distress syndrome (ARDS) have changed due to improvements in mechanical ventilation techniques and support of critically ill patients, by comparing patients from two different periods in the same hospital. We reviewed data from all patients with a diagnosis of ARDS (according to American-European Consensus Conference criteria) who were treated in our multidisciplinary department of intensive care (Erasme Hospital, Brussels) between January 2006 and April 2009 (group B, n=210) and compared them with our previously reported data (January 1993 to February 1995) (group A, n=129). The prevalence of ARDS has decreased (from 2.5% in group A to 1.7% in group B, p<0.001). ARDS patients are now older and sepsis-related ARDS is more common. Multiple transfusion and trauma are less common causes of ARDS than in the past. Intensive care unit length of stay among survivors is shorter (13 +/- 9 versus 17 +/- 17 days, p=0.025), and there was a trend to lower mortality rates in the more recent cohort (46% versus 52%, p=0.158). Multiple organ failure (MOF) was the most common cause of death in both periods. The pattern of ARDS has changed over time in our department. Patients with ARDS are now older and more severely ill. Sepsis-related ARDS is more frequent whereas trauma-related and/or transfusion-related ARDS has decreased. MOF still represents the most frequent cause of death. PMID- 22323570 TI - Safety and efficacy of exercise training in various forms of pulmonary hypertension. AB - The objective of this prospective study was to assess safety and efficacy of exercise training in a large cohort of patients with different forms and World Health Organization (WHO) functional classes of chronic pulmonary hypertension (PH). 183 patients with PH (pulmonary arterial hypertension (PAH), chronic thromboembolic PH and PH due to respiratory or left heart diseases received exercise training in hospital for 3 weeks and continued at home. Adverse events have been monitored during the in-hospital training programme. Efficacy parameters were evaluated at baseline, and after 3 and 15 weeks. After 3 and 15 weeks, patients significantly improved the distance walked in 6 min (6MWD) compared to baseline, scores of quality of life, WHO functional class, peak oxygen consumption, oxygen pulse, heart rate and systolic pulmonary artery pressure at rest and maximal workload. The improvement in 6MWD was similar in patients with different PH forms and functional classes. Even in severely affected patients (WHO functional class IV), exercise training was highly effective. Adverse events, such as respiratory infections, syncope or presyncope, occurred in 13% of patients. Exercise training in PH is an effective but not a completely harmless add-on therapy, even in severely diseased patients, and should be closely monitored. PMID- 22323571 TI - Effect of autoimmune diseases on risk and survival in histology-specific lung cancer. AB - Patients with autoimmune diseases are at an increased risk of cancer due to underlying dysregulation of the immune system or treatment. Data on cancer incidence, mortality and survival after autoimmune diseases would provide further information on the clinical implications. We systematically analysed data on lung cancer in patients diagnosed with 33 different autoimmune diseases. Standardised incidence ratios (SIRs), standardised mortality ratios (SMRs) and hazard ratios (HRs) were calculated for subsequent incident lung cancers or lung cancer deaths up to 2008 in patients hospitalised for autoimmune disease after 1964. Increased risks of lung cancer were recorded for SIRs after 12 autoimmune diseases, SMRs after 11 autoimmune diseases and HRs after two autoimmune diseases. The highest SIRs and SMRs, respectively, were seen after discoid lupus erythematosus (4.71 and 4.80), polymyosistis/dermatomyositis (4.20 and 4.17), systemic lupus erythematosus (2.47 and 2.69), rheumatic fever (2.07 and 2.07) and systemic sclerosis (2.19 and 1.98). Autoimmune disease did not influence survival overall but some autoimmune diseases appeared to impair survival in small cell carcinoma. All autoimmune diseases that had an SIR >2.0 are known to present with lung manifestations, suggesting that the autoimmune process contributes to lung cancer susceptibility. The data on survival are reassuring that autoimmune diseases do not influence prognosis in lung cancer. PMID- 22323572 TI - Transmissible strains of Pseudomonas aeruginosa in cystic fibrosis lung infections. AB - Pseudomonas aeruginosa chronic lung infections are the major cause of morbidity and mortality associated with cystic fibrosis. For many years, the consensus was that cystic fibrosis patients acquire P. aeruginosa from the environment, and hence harbour their own individual clones. However, in the past 15 yrs the emergence of transmissible strains, in some cases associated with greater morbidity and increased antimicrobial resistance, has changed the way that many clinics treat their patients. Here we provide a summary of reported transmissible strains in the UK, other parts of Europe, Australia and North America. In particular, we discuss the prevalence, epidemiology, unusual genotypic and phenotypic features, and virulence of the most intensively studied transmissible strain, the Liverpool epidemic strain. We also discuss the clinical impact of transmissible strains, in particular the diagnostic and infection control approaches adopted to counter their spread. Genomic analysis carried out so far has provided little evidence that transmissibility is due to shared genetic characteristics between different strains. Previous experiences with transmissible strains should help us to learn lessons for the future. In particular, there is a clear need for strain surveillance if emerging problem strains are to be detected before they are widely transmitted. PMID- 22323573 TI - Interobserver agreement in determining non-small cell lung cancer subtype in specimens acquired by EBUS-TBNA. AB - Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) may diagnose suspected lung cancer. Determination of non-small cell lung cancer (NSCLC) subtype may guide therapy in select patients. Small-volume biopsies may be subject to significant interobserver variability in subtype determination. Three pathologists independently reviewed specimens from 60 patients who underwent EBUS-TBNA for diagnosis/staging of suspected/known NSCLC. Smear, haematoxylin and eosin (H&E) and immunohistochemistry (IHC) specimens were reviewed without reference to other specimen types obtained from the same patient. Final diagnoses, and degree of confidence in the diagnosis, were recorded for each specimen. Almost perfect agreement was seen for distinguishing between small cell lung cancer and NSCLC for all specimen types. Agreement in determination of NSCLC subtype for smear, H&E and IHC specimens was slight (kappa=0.095, 95% CI -0.164-0.355), fair (kappa=0.278, 95% CI 0.075-0.481) and moderate (kappa=0.564, 95% CI 0.338-0.740), respectively. Perfect agreement was seen when all three observers were confident of diagnoses made on IHC specimens. Interobserver agreement in interpretation of EBUS-TBNA specimens is moderate for determination of NSCLC subtype. Agreement is highest following examination of IHC specimens. Clinicians should be aware of the degree of pathologist confidence in the tissue diagnosis prior to commencement of subtype-specific therapy for NSCLC. PMID- 22323574 TI - Diagnosis of myocardial infarction following hospitalisation for exacerbation of COPD. AB - Cardiovascular disease is common in chronic obstructive pulmonary disease (COPD) and raised troponin is common in exacerbations. However, the prevalence of myocardial infarction following hospitalisation for exacerbation of COPD is unknown. Patients aged >= 40 yrs hospitalised with acute exacerbation of COPD (n = 242) with >= 10 pack-yrs of cigarette smoking were included in a prospective case series conducted in four hospitals. Patients whose primary presenting complaint was chest pain or who had an alternative diagnosis were excluded. Chest pain histories, serial ECGs and troponin levels were obtained. The mean +/- SD age was 69 +/- 9 yrs; 108 (45%) patients were male and almost half were current smokers. 124 (51%; 95% CI 48-58%) patients had chest pain, which was exertional in 62 (26%). 24 (10%) had raised troponin, among whom, 20 (8.3%; 95% CI 5.1 12.5%) had chest pain and/or serial ECG changes, fulfilling the 2007 Universal Definition of Myocardial Infarction. Neither chest pain (p = 0.77) nor serial ECG changes (p = 0.39) were associated with raised troponin. Raised troponin, chest pain and serial ECG changes are common in patients admitted to hospital with exacerbation of COPD. Overall, one in 12 patients met the criteria for myocardial infarction. Whether these patients would benefit from further cardiac investigation is unknown. PMID- 22323575 TI - Detrended fluctuation analysis of peak expiratory flow and exacerbation frequency in COPD. AB - We investigated whether exacerbation frequency in chronic obstructive pulmonary disease (COPD) was related to an exponent alpha which quantifies self-similarity in daily peak expiratory flow (PEF) and is calculated using detrended fluctuation analysis (DFA). We examined data from COPD patients who recorded an increase in respiratory symptoms and post-bronchodilator PEF on daily diary cards. We also investigated PEF data from a double-blind, placebo-controlled trial of the anti cholinergic agent, tiotropium. In the observational study there were 308 patients with COPD (195 males; mean +/- sd age 68.3 +/- 8.4 yrs, forced expiratory volume in 1 s (FEV(1)) 1.12 +/- 0.46 L, FEV(1) % predicted 44.5 +/- 16.4%). The mean +/- sd alpha over the first year was 0.944 +/- 0.19 and it was positively related to the frequency of exacerbations per year (p=0.009). In the clinical trial, alpha was lower in COPD patients randomised to tiotropium, mean +/- sd 0.87 +/- 0.21 (n=48) than on placebo, mean +/- sd 0.95 +/- 0.19 (n=52; p=0.035). Power analysis showed that fewer patients would be required for clinical studies with alpha as the outcome measure than exacerbation frequency. DFA shows that daily PEF in COPD has long-term correlations which are related to exacerbation frequency. Monitoring of PEF and use of alpha may result in smaller COPD patient sample sizes in trials. PMID- 22323576 TI - Efficacy of a nicotine mouth spray in smoking cessation: a randomised, double blind trial. AB - A nicotine mouth spray has advantages over other acute forms of nicotine replacement therapy, such as a faster uptake of nicotine and faster relief of craving. This multicentre, randomised (2:1), double-blind, placebo-controlled efficacy and safety study evaluated self-reported, carbon monoxide-verified continuous abstinence from smoking from week 2 until weeks 6, 24, and 52 in 479 smokers (>= 1 cigarette per day) who were treated with either active (n=318) or placebo (n=161) spray for 12 weeks and low-intensity counselling at three smoking cessation clinics in Denmark and Germany. Active treatment yielded significantly higher continuous abstinence rates than placebo from week 2 until week 6 (26.1% versus 16.1%; relative success rate (RR) 1.62, 95% CI 1.09-2.41), week 24 (15.7% versus 6.8%; RR 2.30, 95% CI 1.23-4.30), and week 52 (13.8% versus 5.6%; RR 2.48, 95% CI 1.24-4.94). Most adverse events were mild to moderate, and 9.1% of subjects on active spray withdrew due to adverse events, compared to 7.5% on placebo. The overall rate of treatment-related adverse events was 87.4% with active spray versus 71.4% with placebo spray. Nicotine mouth spray delivered significantly higher 6-, 24- and 52-week continuous abstinence rates than placebo. PMID- 22323577 TI - Computed tomography-quantified emphysema distribution is associated with lung function decline. AB - Emphysema distribution is associated with chronic obstructive pulmonary disease. It is, however, unknown whether computed tomography (CT)-quantified emphysema distribution (upper/lower lobe) is associated with lung function decline in heavy (former) smokers. 587 male participants underwent lung CT and pulmonary function testing at baseline and after a median (interquartile range) follow-up of 2.9 (2.8-3.0) yrs. The lungs were automatically segmented based on anatomically defined lung lobes. Severity of emphysema was automatically quantified per anatomical lung lobe and was expressed as the 15th percentile (Hounsfield unit point below which 15% of the low-attenuation voxels are distributed (Perc15)). The CT-quantified emphysema distribution was based on principal component analysis. Linear mixed models were used to assess the association of emphysema distribution with forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC), FEV(1) and FVC decline. Mean +/- SD age was 60.2 +/- 5.4 yrs, mean baseline FEV(1)/FVC was 71.6 +/- 9.0% and overall mean Perc15 was -908.5 +/- 20.9 HU. Participants with upper lobe-predominant CT-quantified emphysema had a lower FEV(1)/FVC, FEV(1) and FVC after follow-up compared with participants with lower lobe-predominant CT-quantified emphysema (p=0.001), independent of the total extent of CT-quantified emphysema. Heavy (former) smokers with upper lobe predominant CT-quantified emphysema have a more rapid decrease in lung function than those with lower lobe-predominant CT-quantified emphysema. PMID- 22323578 TI - TB and MDR/XDR-TB in European Union and European Economic Area countries: managed or mismanaged? AB - In spite of the growing awareness of emerging drug-resistant Mycobacterium tuberculosis, the extent of inappropriate tuberculosis (TB) case management may be underestimated, even in Europe. We evaluated TB case management in the European Union/European Economic Area countries, with special focus on multidrug resistant (MDR) and extensively drug-resistant (XDR)-TB, using a purposely developed, standardised survey tool. National reference centres in five countries representing different geographical, socioeconomic and epidemiological patterns of TB in Europe were surveyed. 40 consecutive, original clinical TB case records (30 MDR/XDR-TB cases) were reviewed in each of the five countries. The findings were recorded and, through the survey tool, compared with previously agreed and identified international standards. Deviations from international standards of TB care were observed in the following areas: surveillance (no information available on patient outcomes); infection control (lack of respiratory isolation rooms/procedures and negative-pressure ventilation rooms); clinical management of TB, MDR-TB and HIV co-infection (inadequate bacteriological diagnosis, regimen selection and treatment duration); laboratory support; and diagnostic/treatment algorithms. Gaps between present international standards of care and the management of MDR/XDR-TB patients were identified. Training, increased awareness, promotion of standards and allocation of appropriate resources are necessary to ensure appropriate care and management as well as to prevent further emergence of drug resistance. PMID- 22323579 TI - Phosphorylation of dedicator of cytokinesis 1 (Dock180) at tyrosine residue Y722 by Src family kinases mediates EGFRvIII-driven glioblastoma tumorigenesis. AB - Glioblastoma, the most common primary malignant cancer of the brain, is characterized by rapid tumor growth and infiltration of tumor cells throughout the brain. These traits cause glioblastomas to be highly resistant to current therapies with a resultant poor prognosis. Although aberrant oncogenic signaling driven by signature genetic alterations, such as EGF receptor (EGFR) gene amplification and mutation, plays a major role in glioblastoma pathogenesis, the responsible downstream mechanisms remain less clear. Here, we report that EGFRvIII (also known as DeltaEGFR and de2-7EGFR), a constitutively active EGFR mutant that is frequently co-overexpressed with EGFR in human glioblastoma, promotes tumorigenesis through Src family kinase (SFK)-dependent phosphorylation of Dock180, a guanine nucleotide exchange factor for Rac1. EGFRvIII induces phosphorylation of Dock180 at tyrosine residue 722 (Dock180(Y722)) and stimulates Rac1-signaling, glioblastoma cell survival and migration. Consistent with this being causal, siRNA knockdown of Dock180 or expression of a Dock180(Y722F) mutant inhibits each of these EGFRvIII-stimulated activities. The SFKs, Src, Fyn, and Lyn, induce phosphorylation of Dock180(Y722) and inhibition of these SFKs by pharmacological inhibitors or shRNA depletion markedly attenuates EGFRvIII induced phosphorylation of Dock180(Y722), Rac1 activity, and glioblastoma cell migration. Finally, phosphorylated Dock180(Y722) is coexpressed with EGFRvIII and phosphorylated Src(Y418) in clinical specimens, and such coexpression correlates with an extremely poor survival in glioblastoma patients. These results suggest that targeting the SFK-p-Dock180(Y722)-Rac1 signaling pathway may offer a novel therapeutic strategy for glioblastomas with EGFRvIII overexpression. PMID- 22323580 TI - Trafficking of gap junction channels at a vertebrate electrical synapse in vivo. AB - Trafficking and turnover of transmitter receptors required to maintain and modify the strength of chemical synapses have been characterized extensively. In contrast, little is known regarding trafficking of gap junction components at electrical synapses. By combining ultrastructural and in vivo physiological analysis at identified mixed (electrical and chemical) synapses on the goldfish Mauthner cell, we show here that gap junction hemichannels are added at the edges of GJ plaques where they dock with hemichannels in the apposed membrane to form cell-cell channels and, simultaneously, that intact junctional regions are removed from centers of these plaques into either presynaptic axon or postsynaptic dendrite. Moreover, electrical coupling is readily modified by intradendritic application of peptides that interfere with endocytosis or exocytosis, suggesting that the strength of electrical synapses at these terminals is sustained, at least in part, by fast (in minutes) turnover of gap junction channels. A peptide corresponding to a region of the carboxy terminus that is conserved in Cx36 and its two teleost homologs appears to interfere with formation of new gap junction channels, presumably by reducing insertion of hemichannels on the dendritic side. Thus, our data indicate that electrical synapses are dynamic structures and that their channels are turned over actively, suggesting that regulated trafficking of connexons may contribute to the modification of gap junctional conductance. PMID- 22323582 TI - Microchimerism in cord blood: mother as anticancer drug. PMID- 22323583 TI - Highly neurotoxic monomeric alpha-helical prion protein. AB - Prion diseases are infectious and belong to the group of protein misfolding neurodegenerative diseases. In these diseases, neuronal dysfunction and death are caused by the neuronal toxicity of a particular misfolded form of their cognate protein. The ability to specifically target the toxic protein conformer or the neuronal death pathway would provide powerful therapeutic approaches to these diseases. The neurotoxic forms of the prion protein (PrP) have yet to be defined but there is evidence suggesting that at least some of them differ from infectious PrP (PrP(Sc)). Herein, without making an assumption about size or conformation, we searched for toxic forms of recombinant PrP after dilution refolding, size fractionation, and systematic biological testing of all fractions. We found that the PrP species most neurotoxic in vitro and in vivo (toxic PrP, TPrP) is a monomeric, highly alpha-helical form of PrP. TPrP caused autophagy, apoptosis, and a molecular signature remarkably similar to that observed in the brains of prion-infected animals. Interestingly, highly alpha helical intermediates have been described for other amyloidogenic proteins but their biological significance remains to be established. We provide unique experimental evidence that a monomeric alpha-helical form of an amyloidogenic protein represents a cytotoxic species. Although toxic PrP has yet to be purified from prion-infected brains, TPrP might be the equivalent of one highly neurotoxic PrP species generated during prion replication. Because TPrP is a misfolded, highly neurotoxic form of PrP reproducing several features of prion-induced neuronal death, it constitutes a useful model to study PrP-induced neurodegenerative mechanisms. PMID- 22323584 TI - Female reproductive tract form drives the evolution of complex sperm morphology. AB - The coevolution of female mate preferences and exaggerated male traits is a fundamental prediction of many sexual selection models, but has largely defied testing due to the challenges of quantifying the sensory and cognitive bases of female preferences. We overcome this difficulty by focusing on postcopulatory sexual selection, where readily quantifiable female reproductive tract structures are capable of biasing paternity in favor of preferred sperm morphologies and thus represent a proximate mechanism of female mate choice when ejaculates from multiple males overlap within the tract. Here, we use phylogenetically controlled generalized least squares and logistic regression to test whether the evolution of female reproductive tract design might have driven the evolution of complex, multivariate sperm form in a family of aquatic beetles. The results indicate that female reproductive tracts have undergone extensive diversification in diving beetles, with remodeling of size and shape of several organs and structures being significantly associated with changes in sperm size, head shape, gains/losses of conjugation and conjugate size. Further, results of Bayesian analyses suggest that the loss of sperm conjugation is driven by elongation of the female reproductive tract. Behavioral and ultrastructural examination of sperm conjugates stored in the female tract indicates that conjugates anchor in optimal positions for fertilization. The results underscore the importance of postcopulatory sexual selection as an agent of diversification. PMID- 22323585 TI - A Y-linked anti-Mullerian hormone duplication takes over a critical role in sex determination. AB - Gonadal sex determination in vertebrates generally follows a sequence of genetically programmed events. In what is seemingly becoming a pattern, all confirmed or current candidate "master" sex-determining genes reported in this group, e.g., SRY in eutherian mammals, DMY/dmrt1bY in medaka, DM-W in the African clawed frog, and DMRT1 in chicken encode transcription factors. In contrast, here we show that a male-specific, duplicated copy of the anti-Mullerian hormone (amh) is implicated in testicular development of the teleost fish Patagonian pejerrey (Odontesthes hatcheri). The gene, termed amhy because it is found in a single metacentric/submetacentric chromosome of XY individuals, is expressed much earlier than the autosomal amh (6 d after fertilization vs. 12 wk after fertilization) and is localized to presumptive Sertoli cells of XY males during testicular differentiation. Moreover, amhy knockdown in XY embryos resulted in the up-regulation of foxl2 and cyp19a1a mRNAs and the development of ovaries. These results are evidence of a functional amh duplication in vertebrates and suggest that amhy may be the master sex-determining gene in this species. If confirmed, this would be a unique instance of a hormone-related gene, a member of the TGF-beta superfamily, in such a role. PMID- 22323586 TI - Central diabetes insipidus associated with impaired renal aquaporin-1 expression in mice lacking liver X receptor beta. AB - The present study demonstrates a key role for the oxysterol receptor liver X receptor beta (LXRbeta) in the etiology of diabetes insipidus (DI). Given free access to water, LXRbeta(-/-) but not LXRalpha(-/-) mice exhibited polyuria (abnormal daily excretion of highly diluted urine) and polydipsia (increased water intake), both features of diabetes insipidus. LXRbeta(-/-) mice responded to 24-h dehydration with a decreased urine volume and increased urine osmolality. To determine whether the DI was of central or nephrogenic origin, we examined the responsiveness of the kidney to arginine vasopressin (AVP). An i.p. injection of AVP to LXRbeta(-/-) mice revealed a partial kidney response: There was no effect on urine volume, but there was a significant increase of urine osmolality, suggesting that DI may be caused by a defect in central production of AVP. In the brain of WT mice LXRbeta was expressed in the nuclei of magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus. In LXRbeta(-/-) mice the expression of AVP was markedly decreased in the magnocellular neurons as well as in urine collected over a 24-h period. The persistent high urine volume after AVP administration was traced to a reduction in aquaporin-1 expression in the kidney of LXRbeta(-/-) mice. The LXR agonist (GW3965) in WT mice elicited an increase in urine osmolality, suggesting that LXRbeta is a key receptor in controlling water balance with targets in both the brain and kidney, and it could be a therapeutic target in disorders of water balance. PMID- 22323587 TI - Experimental viral evolution to specific host MHC genotypes reveals fitness and virulence trade-offs in alternative MHC types. AB - The unprecedented genetic diversity found at vertebrate MHC (major histocompatibility complex) loci influences susceptibility to most infectious and autoimmune diseases. The evolutionary explanation for how these polymorphisms are maintained has been controversial. One leading explanation, antagonistic coevolution (also known as the Red Queen), postulates a never-ending molecular arms race where pathogens evolve to evade immune recognition by common MHC alleles, which in turn provides a selective advantage to hosts carrying rare MHC alleles. This cyclical process leads to negative frequency-dependent selection and promotes MHC diversity if two conditions are met: (i) pathogen adaptation must produce trade-offs that result in pathogen fitness being higher in familiar (i.e., host MHC genotype adapted to) vs. unfamiliar host MHC genotypes; and (ii) this adaptation must produce correlated patterns of virulence (i.e., disease severity). Here we test these fundamental assumptions using an experimental evolutionary approach (serial passage). We demonstrate rapid adaptation and virulence evolution of a mouse-specific retrovirus to its mammalian host across multiple MHC genotypes. Critically, this adaptive response results in trade-offs (i.e., antagonistic pleiotropy) between host MHC genotypes; both viral fitness and virulence is substantially higher in familiar versus unfamiliar MHC genotypes. These data are unique in experimentally confirming the requisite conditions of the antagonistic coevolution model of MHC evolution and providing quantification of fitness effects for pathogen and host. These data help explain the unprecedented diversity of MHC genes, including how disease-causing alleles are maintained. PMID- 22323589 TI - Impact of cross-protective vaccines on epidemiological and evolutionary dynamics of influenza. AB - Large-scale immunization has profoundly impacted control of many infectious diseases such as measles and smallpox because of the ability of vaccination campaigns to maintain long-term herd immunity and, hence, indirect protection of the unvaccinated. In the case of human influenza, such potential benefits of mass vaccination have so far proved elusive. The central difficulty is a considerable viral capacity for immune escape; new pandemic variants, as well as viral escape mutants in seasonal influenza, compromise the buildup of herd immunity from natural infection or deployment of current vaccines. Consequently, most current influenza vaccination programs focus mainly on protection of specific risk groups, rather than mass prophylactic protection. Here, we use epidemiological models to show that emerging vaccine technologies, aimed at broad-spectrum protection, could qualitatively alter this picture. We demonstrate that sustained immunization with such vaccines could--through potentially lowering transmission rates and improving herd immunity--significantly moderate both influenza pandemic and seasonal epidemics. More subtly, phylodynamic models indicate that widespread cross-protective immunization could slow the antigenic evolution of seasonal influenza; these effects have profound implications for a transition to mass vaccination strategies against human influenza, and for the management of antigenically variable viruses in general. PMID- 22323590 TI - Hydrogen sulfide (H2S) metabolism in mitochondria and its regulatory role in energy production. AB - Although many types of ancient bacteria and archea rely on hydrogen sulfide (H(2)S) for their energy production, eukaryotes generate ATP in an oxygen dependent fashion. We hypothesize that endogenous H(2)S remains a regulator of energy production in mammalian cells under stress conditions, which enables the body to cope with energy demand when oxygen supply is insufficient. Cystathionine gamma-lyase (CSE) is a major H(2)S-producing enzyme in the cardiovascular system that uses cysteine as the main substrate. Here we show that CSE is localized only in the cytosol, not in mitochondria, of vascular smooth-muscle cells (SMCs) under resting conditions, revealed by Western blot analysis and confocal microscopy of SMCs transfected with GFP-tagged CSE plasmid. After SMCs were exposed to A23187, thapsigargin, or tunicamycin, intracellular calcium level was increased, and CSE translocated from the cytosol to mitochondria. CSE was coimmunoprecipitated with translocase of the outer membrane 20 (Tom20) in mitochondrial membrane. Tom20 siRNA significantly inhibited mitochondrial translocation of CSE and mitochondrial H(2)S production. The cysteine level inside mitochondria is approximately three times that in the cytosol. Translocation of CSE to mitochondria metabolized cysteine, produced H(2)S inside mitochondria, and increased ATP production. Inhibition of CSE activity reversed A23187-stimulated mitochondrial ATP production. H(2)S improved mitochondrial ATP production in SMCs with hypoxia, which alone decreased ATP production. These results suggest that translocation of CSE to mitochondria on specific stress stimulations is a unique mechanism to promote H(2)S production inside mitochondria, which subsequently sustains mitochondrial ATP production under hypoxic conditions. PMID- 22323591 TI - Temporally-independent functional modes of spontaneous brain activity. AB - Resting-state functional magnetic resonance imaging has become a powerful tool for the study of functional networks in the brain. Even "at rest," the brain's different functional networks spontaneously fluctuate in their activity level; each network's spatial extent can therefore be mapped by finding temporal correlations between its different subregions. Current correlation-based approaches measure the average functional connectivity between regions, but this average is less meaningful for regions that are part of multiple networks; one ideally wants a network model that explicitly allows overlap, for example, allowing a region's activity pattern to reflect one network's activity some of the time, and another network's activity at other times. However, even those approaches that do allow overlap have often maximized mutual spatial independence, which may be suboptimal if distinct networks have significant overlap. In this work, we identify functionally distinct networks by virtue of their temporal independence, taking advantage of the additional temporal richness available via improvements in functional magnetic resonance imaging sampling rate. We identify multiple "temporal functional modes," including several that subdivide the default-mode network (and the regions anticorrelated with it) into several functionally distinct, spatially overlapping, networks, each with its own pattern of correlations and anticorrelations. These functionally distinct modes of spontaneous brain activity are, in general, quite different from resting-state networks previously reported, and may have greater biological interpretability. PMID- 22323592 TI - A neurophysiological-metabolic model for burst suppression. AB - Burst suppression is an electroencepholagram (EEG) pattern in which high-voltage activity alternates with isoelectric quiescence. It is characteristic of an inactivated brain and is commonly observed at deep levels of general anesthesia, hypothermia, and in pathological conditions such as coma and early infantile encephalopathy. We propose a unifying mechanism for burst suppression that accounts for all of these conditions. By constructing a biophysical computational model, we show how the prevailing features of burst suppression may arise through the interaction between neuronal dynamics and brain metabolism. In each condition, the model suggests that a decrease in cerebral metabolic rate, coupled with the stabilizing properties of ATP-gated potassium channels, leads to the characteristic epochs of suppression. Consequently, the model makes a number of specific predictions of experimental and clinical relevance. PMID- 22323593 TI - Approximately diagonalizing matrices over C(Y). AB - Let X be a compact metric space which is locally absolutely retract and let phi: C(X) -> C(Y,M(n)) be a unital homomorphism, where Y is a compact metric space with dim Y <= 2. It is proved that there exists a sequence of n continuous maps alpha(i,m): Y -> X (i = 1,2,...,n) and a sequence of sets of mutually orthogonal rank-one projections {p(1,m),p(2,m),...,p(n,m)} C(Y,M(n)) such that [see formula]. This is closely related to the Kadison diagonal matrix question. It is also shown that this approximate diagonalization could not hold in general when dim Y >= 3. PMID- 22323594 TI - Profile of Jane I. Guyer. PMID- 22323595 TI - Defective transcription initiation causes postnatal growth failure in a mouse model of nucleotide excision repair (NER) progeria. AB - Nucleotide excision repair (NER) defects are associated with cancer, developmental disorders and neurodegeneration. However, with the exception of cancer, the links between defects in NER and developmental abnormalities are not well understood. Here, we show that the ERCC1-XPF NER endonuclease assembles on active promoters in vivo and facilitates chromatin modifications for transcription during mammalian development. We find that Ercc1(-/-) mice demonstrate striking physiological, metabolic and gene expression parallels with Taf10(-/-) animals carrying a liver-specific transcription factor II D (TFIID) defect in transcription initiation. Promoter occupancy studies combined with expression profiling in the liver and in vitro differentiation cell assays reveal that ERCC1-XPF interacts with TFIID and assembles with POL II and the basal transcription machinery on promoters in vivo. Whereas ERCC1-XPF is required for the initial activation of genes associated with growth, it is dispensable for ongoing transcription. Recruitment of ERCC1-XPF on promoters is accompanied by promoter-proximal DNA demethylation and histone marks associated with active hepatic transcription. Collectively, the data unveil a role of ERCC1/XPF endonuclease in transcription initiation establishing its causal contribution to NER developmental disorders. PMID- 22323596 TI - Small molecule antagonist reveals seizure-induced mediation of neuronal injury by prostaglandin E2 receptor subtype EP2. AB - With interest waning in the use of cyclooxygenase-2 (COX-2) inhibitors for inflammatory disease, prostaglandin receptors provide alternative targets for the treatment of COX-2-mediated pathological conditions in both the periphery and the central nervous system. Activation of prostaglandin E2 receptor (PGE(2)) subtype EP2 promotes inflammation and is just beginning to be explored as a therapeutic target. To better understand physiological and pathological functions of the prostaglandin EP2 receptor, we developed a suite of small molecules with a 3-aryl acrylamide scaffold as selective EP2 antagonists. The 12 most potent compounds displayed competitive antagonism of the human EP2 receptor with K(B) 2-20 nM in Schild regression analysis and 268- to 4,730-fold selectivity over the prostaglandin EP4 receptor. A brain-permeant compound completely suppressed the up-regulation of COX-2 mRNA in rat cultured microglia by EP2 activation and significantly reduced neuronal injury in hippocampus when administered in mice beginning 1 h after termination of pilocarpine-induced status epilepticus. The salutary actions of this novel group of antagonists raise the possibility that selective block of EP2 signaling via small molecules can be an innovative therapeutic strategy for inflammation-related brain injury. PMID- 22323597 TI - Intratumoral heterogeneity of receptor tyrosine kinases EGFR and PDGFRA amplification in glioblastoma defines subpopulations with distinct growth factor response. AB - Glioblastoma (GBM) is distinguished by a high degree of intratumoral heterogeneity, which extends to the pattern of expression and amplification of receptor tyrosine kinases (RTKs). Although most GBMs harbor RTK amplifications, clinical trials of small-molecule inhibitors targeting individual RTKs have been disappointing to date. Activation of multiple RTKs within individual GBMs provides a theoretical mechanism of resistance; however, the spectrum of functional RTK dependence among tumor cell subpopulations in actual tumors is unknown. We investigated the pattern of heterogeneity of RTK amplification and functional RTK dependence in GBM tumor cell subpopulations. Analysis of The Cancer Genome Atlas GBM dataset identified 34 of 463 cases showing independent focal amplification of two or more RTKs, most commonly platelet-derived growth factor receptor alpha (PDGFRA) and epidermal growth factor receptor (EGFR). Dual color fluorescence in situ hybridization was performed on eight samples with EGFR and PDGFRA amplification, revealing distinct tumor cell subpopulations amplified for only one RTK; in all cases these predominated over cells amplified for both. Cell lines derived from coamplified tumors exhibited genotype selection under RTK targeted ligand stimulation or pharmacologic inhibition in vitro. Simultaneous inhibition of both EGFR and PDGFR was necessary for abrogation of PI3 kinase pathway activity in the mixed population. DNA sequencing of isolated subpopulations establishes a common clonal origin consistent with late or ongoing divergence of RTK genotype. This phenomenon is especially common among tumors with PDGFRA amplification: overall, 43% of PDGFRA-amplified GBM were found to have amplification of EGFR or the hepatocyte growth factor receptor gene (MET) as well. PMID- 22323598 TI - Neutralizing antibodies against the preactive form of respiratory syncytial virus fusion protein offer unique possibilities for clinical intervention. AB - Human respiratory syncytial virus (hRSV) is the most important viral agent of pediatric respiratory infections worldwide. The only specific treatment available today is a humanized monoclonal antibody (Palivizumab) directed against the F glycoprotein, administered prophylactically to children at very high risk of severe hRSV infections. Palivizumab, as most anti-F antibodies so far described, recognizes an epitope that is shared by the two conformations in which hRSV_F can fold, the metastable prefusion form and the highly stable postfusion conformation. We now describe a unique class of antibodies specific for the prefusion form of this protein that account for most of the neutralizing activity of either a rabbit serum raised against a vaccinia virus recombinant expressing hRSV_F or a human Ig preparation (Respigam), which was used for prophylaxis before Palivizumab. These antibodies therefore offer unique possibilities for immune intervention against hRSV, and their production should be assessed in trials of hRSV vaccines. PMID- 22323599 TI - Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27). AB - Trimethylation of histone H3 on lysine 27 (H3K27me3) is a repressive posttranslational modification mediated by the histone methyltransferase EZH2. EZH2 is a component of the polycomb repressive complex 2 and is overexpressed in many cancers. In B-cell lymphomas, its substrate preference is frequently altered through somatic mutation of the EZH2 Y641 residue. Herein, we identify mutation of EZH2 A677 to a glycine (A677G) among lymphoma cell lines and primary tumor specimens. Similar to Y641 mutant cell lines, an A677G mutant cell line revealed aberrantly elevated H3K27me3 and decreased monomethylated H3K27 (H3K27me1) and dimethylated H3K27 (H3K27me2). A677G EZH2 possessed catalytic activity with a substrate specificity that was distinct from those of both WT EZH2 and Y641 mutants. Whereas WT EZH2 displayed a preference for substrates with less methylation [unmethylated H3K27 (H3K27me0):me1:me2 k(cat)/K(m) ratio = 9:6:1] and Y641 mutants preferred substrates with greater methylation (H3K27me0:me1:me2 k(cat)/K(m) ratio = 1:2:13), the A677G EZH2 demonstrated nearly equal efficiency for all three substrates (H3K27me0:me1:me2 k(cat)/K(m) ratio = 1.1:0.6:1). When transiently expressed in cells, A677G EZH2, but not WT EZH2, increased global H3K27me3 and decreased H3K27me2. Structural modeling of WT and mutant EZH2 suggested that the A677G mutation acquires the ability to methylate H3K27me2 through enlargement of the lysine tunnel while preserving activity with H3K27me0/me1 substrates through retention of the Y641 residue that is crucial for orientation of these smaller substrates. This mutation highlights the interplay between Y641 and A677 residues in the substrate specificity of EZH2 and identifies another lymphoma patient population that harbors an activating mutation of EZH2. PMID- 22323600 TI - Forkhead box N4 (Foxn4) activates Dll4-Notch signaling to suppress photoreceptor cell fates of early retinal progenitors. AB - The generation of diverse neuronal types and subtypes from multipotent progenitors during development is crucial for assembling functional neural circuits in the adult central nervous system. During mouse retinogenesis, early retinal progenitors give rise to several cell types, including ganglion, amacrine, horizontal, cone, and rod cells. It is unknown at present how each of these fates is selected from the multiple neuronal fates available to the early progenitor. By using a combination of bioinformatic, genetic, and biochemical approaches, we investigated the mechanism by which Foxn4 selects the amacrine and horizontal cell fates from multipotential retinal progenitors. These studies indicate that Foxn4 has an intrinsic activity to suppress the alternative photoreceptor cell fates of early retinal progenitors by selectively activating Dll4-Notch signaling. Gene expression and conditional ablation analyses reveal that Dll4 is directly activated by Foxn4 via phylogenetically conserved enhancers and that Dll4 can partly mediate the Foxn4 function by serving as a major Notch ligand to expand the progenitor pool and limit photoreceptor production. Our data together define a Foxn4-mediated molecular and signaling pathway that underlies the suppression of alternative cell fates of early retinal progenitors. PMID- 22323601 TI - SWI2/SNF2 chromatin remodeling ATPases overcome polycomb repression and control floral organ identity with the LEAFY and SEPALLATA3 transcription factors. AB - Patterning of the floral organs is exquisitely controlled and executed by four classes of homeotic regulators. Among these, the class B and class C floral homeotic regulators are of central importance as they specify the male and female reproductive organs. Inappropriate induction of the class B gene APETALA3 (AP3) and the class C gene AGAMOUS (AG) causes reduced reproductive fitness and is prevented by polycomb repression. At the onset of flower patterning, polycomb repression needs to be overcome to allow induction of AP3 and AG and formation of the reproductive organs. We show that the SWI2/SNF2 chromatin-remodeling ATPases SPLAYED (SYD) and BRAHMA (BRM) are redundantly required for flower patterning and for the activation of AP3 and AG. The SWI2/SNF2 ATPases are recruited to the regulatory regions of AP3 and AG during flower development and physically interact with two direct transcriptional activators of class B and class C gene expression, LEAFY (LFY) and SEPALLATA3 (SEP3). SYD and LFY association with the AP3 and AG regulatory loci peaks at the same time during flower patterning, and SYD binding to these loci is compromised in lfy and lfy sep3 mutants. This suggests a mechanism for SWI2/SNF2 ATPase recruitment to these loci at the right stage and in the correct cells. SYD and BRM act as trithorax proteins, and the requirement for SYD and BRM in flower patterning can be overcome by partial loss of polycomb activity in curly leaf (clf) mutants, implicating the SWI2/SNF2 chromatin remodelers in reversal of polycomb repression. PMID- 22323602 TI - Actin bends over backward for directional branching. PMID- 22323603 TI - AgRP neurons: the foes of reproduction in leptin-deficient obese subjects. PMID- 22323604 TI - TDP-43 promotes microRNA biogenesis as a component of the Drosha and Dicer complexes. AB - Although aberrant microRNA (miRNA) expression is linked to human diseases including cancer, the mechanisms that regulate the expression of each individual miRNA remain largely unknown. TAR DNA-binding protein-43 (TDP-43) is homologous to the heterogeneous nuclear ribonucleoproteins (hnRNPs), which are involved in RNA processing, and its abnormal cellular distribution is a key feature of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), two neurodegenerative diseases. Here, we show that TDP-43 facilitates the production of a subset of precursor miRNAs (pre-miRNAs) by both interacting with the nuclear Drosha complex and binding directly to the relevant primary miRNAs (pri-miRNAs). Furthermore, cytoplasmic TDP-43, which interacts with the Dicer complex, promotes the processing of some of these pre-miRNAs via binding to their terminal loops. Finally, we show that involvement of TDP-43 in miRNA biogenesis is indispensable for neuronal outgrowth. These results support a previously uncharacterized role for TDP-43 in posttranscriptional regulation of miRNA expression in both the nucleus and the cytoplasm. PMID- 22323605 TI - Identification of innate immunity elicitors using molecular signatures of natural selection. AB - The innate immune system is an ancient and broad-spectrum defense system found in all eukaryotes. The detection of microbial elicitors results in the up-regulation of defense-related genes and the elicitation of inflammatory and apoptotic responses. These innate immune responses are the front-line barrier against disease because they collectively suppress the growth of the vast majority of invading microbes. Despite their critical role, we know remarkably little about the diversity of immune elicitors. To address this paucity, we reasoned that hosts are more likely to evolve recognition to "core" pathogen proteins under strong negative selection for the maintenance of essential cellular functions, whereas repeated exposure to host-defense responses will impose strong positive selective pressure for elicitor diversification to avoid host recognition. Therefore, we hypothesized that novel bacterial elicitors can be identified through these opposing forces of natural selection. We tested this hypothesis by examining the genomes of six bacterial phytopathogens and identifying 56 candidate elicitors that have an excess of positively selected residues in a background of strong negative selection. We show that these positively selected residues are atypically clustered, similar to patterns seen in the few well characterized elicitors. We then validated selected candidate elicitors by showing that they induce Arabidopsis thaliana innate immunity in functional (virulence suppression) and cellular (callose deposition) assays. These finding provide targets for the study of host-pathogen interactions and applied research into alternative antimicrobial treatments. PMID- 22323606 TI - Active maintenance of nuclear actin by importin 9 supports transcription. AB - Besides its essential and well established role as a component of the cytoskeleton, actin is also present in the cell nucleus, where it has been linked to many processes that control gene expression. For example, nuclear actin regulates the activity of specific transcription factors, associates with all three RNA polymerases, and is a component of many chromatin remodelling complexes. Despite the fact that two export receptors, Crm1 and exportin 6, have been linked to nuclear export of actin, the mechanism by which actin enters the nucleus to elicit these essential functions has not been determined. It is also unclear whether actin is actively exchanged between the nucleus and the cytoplasm, and whether this connection has any functional significance for the cell. By applying a variety of live-cell imaging techniques we revealed that actin constantly shuttles in and out of the nucleus. The fast transport rates, which depend on the availability of actin monomers, suggest an active transport mechanism in both directions. Importantly, we identified importin 9 as the nuclear import factor for actin. Furthermore, our RNAi experiments showed that the active maintenance of nuclear actin levels by importin 9 is required for maximal transcriptional activity. Measurements of nuclear export rates and depletion studies also clarified that nuclear export of actin is mediated by exportin 6, and not by Crm1. These results demonstrate that cytoplasmic and nuclear actin pools are dynamically connected and identify the nuclear import and export mechanisms of actin. PMID- 22323607 TI - Interdomain dynamics and coactivation of the mRNA decapping enzyme Dcp2 are mediated by a gatekeeper tryptophan. AB - Conformational dynamics in bilobed enzymes can be used to regulate their activity. One such enzyme, the eukaryotic decapping enzyme Dcp2, controls the half-life of mRNA by cleaving the 5' cap structure, which exposes a monophosphate that is efficiently degraded by exonucleases. Decapping by Dcp2 is thought to be controlled by an open-to-closed transition involving formation of a composite active site with two domains sandwiching substrate, but many details of this process are not understood. Here, using NMR spectroscopy and enzyme kinetics, we show that Trp43 of Schizosaccharomyces pombe Dcp2 is a conserved gatekeeper of this open-to-closed transition. We find that Dcp2 samples multiple conformations in solution on the millisecond-microsecond timescale. Mutation of the gatekeeper tryptophan abolishes the dynamic behavior of Dcp2 and attenuates coactivation by a yeast enhancer of decapping (Edc1). Our results determine the dynamics of the open-to-closed transition in Dcp2, suggest a structural pathway for coactivation, predict that Dcp1 directly contacts the catalytic domain of Dcp2, and show that coactivation of decapping by Dcp2 is linked to formation of the composite active site. PMID- 22323608 TI - Surprising complexity of the Asf1 histone chaperone-Rad53 kinase interaction. AB - The histone chaperone Asf1 and the checkpoint kinase Rad53 are found in a complex in budding yeast cells in the absence of genotoxic stress. Our data suggest that this complex involves at least three interaction sites. One site involves the H3 binding surface of Asf11 with an as yet undefined surface of Rad53. A second site is formed by the Rad53-FHA1 domain binding to Asf1-T(270) phosphorylated by casein kinase II. The third site involves the C-terminal 21 amino acids of Rad53 bound to the conserved Asf1 N-terminal domain. The structure of this site showed that the Rad53 C-terminus binds Asf1 in a remarkably similar manner to peptides derived from the histone cochaperones HirA and CAF-I. We call this binding motif, (R/K)R(I/A/V) (L/P), the AIP box for Asf1-Interacting Protein box. Furthermore, C terminal Rad53-F(820) binds the same pocket of Asf1 as does histone H4-F(100). Thus Rad53 competes with histones H3-H4 and cochaperones HirA/CAF-I for binding to Asf1. Rad53 is phosphorylated and activated upon genotoxic stress. The Asf1 Rad53 complex dissociated when cells were treated with hydroxyurea but not methyl methane-sulfonate, suggesting a regulation of the complex as a function of the stress. We identified a rad53 mutation that destabilized the Asf1-Rad53 complex and increased the viability of rad9 and rad24 mutants in conditions of genotoxic stress, suggesting that complex stability impacts the DNA damage response. PMID- 22323609 TI - STK33 kinase inhibitor BRD-8899 has no effect on KRAS-dependent cancer cell viability. AB - Approximately 30% of human cancers harbor oncogenic gain-of-function mutations in KRAS. Despite interest in KRAS as a therapeutic target, direct blockade of KRAS function with small molecules has yet to be demonstrated. Based on experiments that lower mRNA levels of protein kinases, KRAS-dependent cancer cells were proposed to have a unique requirement for the serine/threonine kinase STK33. Thus, it was suggested that small-molecule inhibitors of STK33 might have therapeutic benefit in these cancers. Here, we describe the development of selective, low nanomolar inhibitors of STK33's kinase activity. The most potent and selective of these, BRD8899, failed to kill KRAS-dependent cells. While several explanations for this result exist, our data are most consistent with the view that inhibition of STK33's kinase activity does not represent a promising anti-KRAS therapeutic strategy. PMID- 22323610 TI - Significance analysis of xMap cytokine bead arrays. AB - Highly multiplexed assays using antibody coated, fluorescent (xMap) beads are widely used to measure quantities of soluble analytes, such as cytokines and antibodies in clinical and other studies. Current analyses of these assays use methods based on standard curves that have limitations in detecting low or high abundance analytes. Here we describe SAxCyB (Significance Analysis of xMap Cytokine Beads), a method that uses fluorescence measurements of individual beads to find significant differences between experimental conditions. We show that SAxCyB outperforms conventional analysis schemes in both sensitivity (low fluorescence) and robustness (high variability) and has enabled us to find many new differentially expressed cytokines in published studies. PMID- 22323611 TI - A serpentinite-hosted ecosystem in the Southern Mariana Forearc. AB - Several varieties of seafloor hydrothermal vents with widely varying fluid compositions and temperatures and vent communities occur in different tectonic settings. The discovery of the Lost City hydrothermal field in the Mid-Atlantic Ridge has stimulated interest in the role of serpentinization of peridotite in generating H(2)- and CH(4)-rich fluids and associated carbonate chimneys, as well as in the biological communities supported in highly reduced, alkaline environments. Abundant vesicomyid clam communities associated with a serpentinite hosted hydrothermal vent system in the southern Mariana forearc were discovered during a DSV Shinkai 6500 dive in September 2010. We named this system the "Shinkai Seep Field (SSF)." The SSF appears to be a serpentinite-hosted ecosystem within a forearc (convergent margin) setting that is supported by fault controlled fluid pathways connected to the decollement of the subducting slab. The discovery of the SSF supports the prediction that serpentinite-hosted vents may be widespread on the ocean floor. The discovery further indicates that these serpentinite-hosted low-temperature fluid vents can sustain high-biomass communities and has implications for the chemical budget of the oceans and the distribution of abyssal chemosynthetic life. PMID- 22323612 TI - DNA cleavage and opening reactions of human topoisomerase IIalpha are regulated via Mg2+-mediated dynamic bending of gate-DNA. AB - Topoisomerase II resolves intrinsic topological problems of double-stranded DNA. As part of its essential cellular functions, the enzyme generates DNA breaks, but the regulation of this potentially dangerous process is not well understood. Here we report single-molecule fluorescence experiments that reveal a previously uncharacterized sequence of events during DNA cleavage by topoisomerase II: nonspecific DNA binding, sequence-specific DNA bending, and stochastic cleavage of DNA. We have identified unexpected structural roles of Mg(2+) ions coordinated in the TOPRIM (topoisomerase-primase) domain in inducing cleavage-competent DNA bending. A break at one scissile bond dramatically stabilized DNA bending, explaining how two scission events in opposing strands can be coordinated to achieve a high probability of double-stranded cleavage. Clamping of the protein N gate greatly enhanced the rate and degree of DNA bending, resulting in a significant stimulation of the DNA cleavage and opening reactions. Our data strongly suggest that the accurate cleavage of DNA by topoisomerase II is regulated through a tight coordination with DNA bending. PMID- 22323613 TI - Possible mechanisms of interaction between statins and vitamin D. PMID- 22323614 TI - A ring calcified benign thymoma in a patient with asbestos exposure. AB - The differential diagnosis of a mediastinal mass with ring calcification on chest X-ray includes thymoma,dermoid tumour, teratoma, neurogenic tumours and lymphadenopathy. Cross-sectional imaging via CT can aid diagnosis. This case may also demonstrate an association between asbestos exposure and thymoma calcification. PMID- 22323615 TI - Thromboneurosis. PMID- 22323616 TI - Hypoxic-ischaemic brain injury: imaging and neurophysiology abnormalities related to outcome. AB - BACKGROUND: The outcome for patients with hypoxic-ischaemic brain injury (HIBI) is often poor. It is important to establish an accurate prognosis as soon as possible after the insult to guide management. Clinical assessment is not reliable and ancillary investigations, particularly imaging and EEG, are needed to understand the severity of brain injury and the likely outcome. METHODS: We undertook a retrospective study of 39 patients on an intensive therapy unit (ITU) with HIBI who were referred for MRI. The patients were seen consecutively >57 months. HIBI was due to a variety of insults causing cardiac arrest, hypoperfusion or isolated hypoxia. RESULTS: The outcome was poor, 29 patients died, 7 were left severely disabled and only 3 made a good recovery. Characteristic imaging changes were seen on MRI. These included extensive changes in the cortex and the deep grey matter present on diffusion-weighted imaging (DWI) and T2-weighted imaging within 6 days of the insult. In other patients, different patterns of involvement of the cortex and basal ganglia occurred. There was no significant difference in the outcome or imaging appearances according to aetiology. A poor prognosis was consistently associated with a non- or poorly responsive EEG rhythm and the presence of periodic generalized phenomena with a very low-voltage background activity. CONCLUSION: In this retrospective study of patients with HIBI, MRI and EEG provided valuable information concerning prognosis. PMID- 22323617 TI - Quality initiatives: lean approach to improving performance and efficiency in a radiology department. AB - Many hospital radiology departments are adopting "lean" methods developed in automobile manufacturing to improve operational efficiency, eliminate waste, and optimize the value of their services. The lean approach, which emphasizes process analysis, has particular relevance to radiology departments, which depend on a smooth flow of patients and uninterrupted equipment function for efficient operation. However, the application of lean methods to isolated problems is not likely to improve overall efficiency or to produce a sustained improvement. Instead, the authors recommend a gradual but continuous and comprehensive "lean transformation" of work philosophy and workplace culture. Fundamental principles that must consistently be put into action to achieve such a transformation include equal involvement of and equal respect for all staff members, elimination of waste, standardization of work processes, improvement of flow in all processes, use of visual cues to communicate and inform, and use of specific tools to perform targeted data collection and analysis and to implement and guide change. Many categories of lean tools are available to facilitate these tasks: value stream mapping for visualizing the current state of a process and identifying activities that add no value; root cause analysis for determining the fundamental cause of a problem; team charters for planning, guiding, and communicating about change in a specific process; management dashboards for monitoring real-time developments; and a balanced scorecard for strategic oversight and planning in the areas of finance, customer service, internal operations, and staff development. PMID- 22323618 TI - Informatics in radiology: postprocessing pitfalls in using CT for automatic and semiautomatic determination of global left ventricular function. AB - Recent advances in technical capabilities of computed tomographic (CT) scanners, including an increasing number of detector rows, improved spatial and temporal resolution, and the development of retrospective gating, have allowed the acquisition of four-dimensional (4D) datasets of the beating heart. As a result, the heart can be visualized in different phases and CT datasets can be used to assess cardiac function. Many software packages currently exist that allow automatic or semiautomatic evaluation of left ventricular function on the basis of 4D CT datasets. The level of automation varies from extensive, completely manual segmentation by the user to fully automatic evaluation of left ventricular function without any user interaction. Although the reproducibility of functional parameter assessment is reported to be high and intersoftware variability low for larger groups of patients, significant differences can exist among measurements obtained with different software tools from the same dataset. Thus, careful review of automatically or semiautomatically obtained results is required. PMID- 22323619 TI - Molecular signatures to define spermatogenic cells in common marmoset (Callithrix jacchus). AB - Germ cell development is a fundamental process required to produce offspring. The developmental program of spermatogenesis has been assumed to be similar among mammals. However, recent studies have revealed differences in the molecular properties of primate germ cells compared with the well-characterized mouse germ cells. This may prevent simple application of rodent insights into higher primates. Therefore, thorough investigation of primate germ cells is necessary, as this may lead to the development of more appropriate animal models. The aim of this study is to define molecular signatures of spermatogenic cells in the common marmoset, Callithrix jacchus. Interestingly, NANOG, PRDM1, DPPA3 (STELLA), IFITM3, and ZP1 transcripts, but no POU5F1 (OCT4), were detected in adult marmoset testis. Conversely, mouse testis expressed Pou5f1 but not Nanog, Prdm1, Dppa3, Ifitm3, and Zp1. Other previously described mouse germ cell markers were conserved in marmoset and mouse testes. Intriguingly, marmoset spermatogenic cells underwent dynamic protein expression in a developmental stage-specific manner; DDX4 (VASA) protein was present in gonocytes, diminished in spermatogonial cells, and reexpressed in spermatocytes. To investigate epigenetic differences between adult marmoset and mice, DNA methylation analyses identified unique epigenetic profiles to marmoset and mice. Marmoset NANOG and POU5F1 promoters in spermatogenic cells exhibited a methylation status opposite to that in mice, while the DDX4 and LEFTY1 loci, as well as imprinted genes, displayed an evolutionarily conserved methylation pattern. Marmosets have great advantages as models for human reproductive biology and are also valuable as experimental nonhuman primates; thus, the current study provides an important platform for primate reproductive biology, including possible applications to humans. PMID- 22323620 TI - Specialized distribution of the histone methyltransferase Ezh2 in the nuclear apical region of round spermatids and its interaction with the histone variant H1t2. AB - The formation of sperm requires tightly regulated gene expression and unique chromatin remodeling. In the present study, we investigated the spermatogenic distribution of the lysine-specific histone H3 methyltransferase Ezh2 in mice. The distribution of Ezh2 was highly regulated with its localization predominantly restricted to round spermatids in the perinuclear acrosome region. This localization is concomitant with the dramatic epigenetic reorganization that occurs during spermiogenesis leading to an extreme compaction of the chromatin. Spermiogenesis involves the incorporation of sperm-specific nuclear proteins, including the testis-specific histone variant H1t2. Using immunofluorescence, Ezh2 was shown to juxtapose H1t2, and an interaction in chromatin was confirmed by immunoprecipitation. These findings suggest that, in the testis, the apical region of the round spermatid nucleus could be a specialized epigenetic region where methylation of histones serves a role in the spermiogenic chromatin remodeling and that Ezh2 might be a key effector of this event. PMID- 22323621 TI - Editorial commentary. PMID- 22323622 TI - Imaging diagnosis, transurethral endoscopic observation, and management of 43 cases of persistent and refractory hematospermia. AB - The goal of this study was to explore minimally invasive transurethral imaging and surgery for the treatment of severe, persistent hematospermia in cases that were refractory to conservative treatments. The study included 43 patients (aged 22-77 years; average, 44.6 years) with long-lasting, severe hematospermia, accompanied by discomfort or pain in the lumbosacral or perineal region, dysuria, frequent micturition, decreased semen volume, and/or azoospermia. Patient symptoms had persisted for 1 to 10 years (average, 5.3 years). Computed tomography or magnetic resonance imaging of each patient was evaluated, and transurethral surgery was performed. The causes of hematospermia were identified in all 43 patients, and their ejaculatory duct obstruction or seminal vesiculitis was successfully treated. No serious intraoperative or postoperative complications occurred. Pathologic analyses revealed that all of the resected or biopsied seminal vesicle tissues had chronic nonspecific inflammation in the seminal vesicle wall, and no tumors were identified. Preoperative symptomology of hematospermia disappeared in all patients followed up for 2 to 30 months (average, 16 months). A single patient experienced recurrence at 11 months and had a second minimally invasive surgery that was curative. A total of 95.3% (41 of 43) of the patients experienced normal orgasmic intensity after surgery. Magnetic resonance imaging is a valuable and accurate diagnostic method for the identification of causative factors underlying hematospermia. Transurethral dilation of ejaculatory ducts, incision of the verumontanum or the distal end of the ejaculatory ducts, and incision or resection of the relevant cysts represent simple, safe, and reliable approaches for the management of refractory cases of hematospermia that do not respond to conservative treatments. PMID- 22323623 TI - Diet, obesity, and prostate health: are we missing the link? AB - Prostate problems, such as benign prostatic hyperplasia, prostatic intra epithelial neoplasia, prostatitis, and prostate cancer have been recognized as problems largely related to androgens and genetic factors. They affect a large fraction of the elderly population, contributing significantly to morbidity and mortality. Estrogen has also now been recognized as one of the important regulators of prostate growth. Diet, general health, and obesity were disregarded as the causative or complicating factors until very recently. Increasing episodes of prostate problems, complications in overweight/obese individuals, or both have attracted attention toward these contemporary risk factors. Prostate problems are reportedly less frequent or less severe in areas in which a plant-based diet is predominant. Consumption of certain fatty acids, particularly of animal origin, has been correlated with increased prostate problems. As adipose tissue is increasingly being regarded as hormonally active tissue, high body fat and obesity need in-depth exploration to understand the associated risk of prostate problems. Adipose tissue is now known to affect circulating levels of several bioactive messengers and therefore could affect the risk of developing prostate problems in addition to several other well recognized health problems. Nevertheless, increased plasma volume, excess tissue growth, and fat deposition could affect resection and number of biopsies required, thus adding further complications because of a delayed diagnosis. In short, evidence is gathering to support the influence of diet and obesity on prostate health. In this review article, we have tried to make this connection more apparent using supporting published data. PMID- 22323624 TI - Decoding conjunctions of direction-of-motion and binocular disparity from human visual cortex. AB - Motion and binocular disparity are two features in our environment that share a common correspondence problem. Decades of psychophysical research dedicated to understanding stereopsis suggest that these features interact early in human visual processing to disambiguate depth. Single-unit recordings in the monkey also provide evidence for the joint encoding of motion and disparity across much of the dorsal visual stream. Here, we used functional MRI and multivariate pattern analysis to examine where in the human brain conjunctions of motion and disparity are encoded. Subjects sequentially viewed two stimuli that could be distinguished only by their conjunctions of motion and disparity. Specifically, each stimulus contained the same feature information (leftward and rightward motion and crossed and uncrossed disparity) but differed exclusively in the way these features were paired. Our results revealed that a linear classifier could accurately decode which stimulus a subject was viewing based on voxel activation patterns throughout the dorsal visual areas and as early as V2. This decoding success was conditional on some voxels being individually sensitive to the unique conjunctions comprising each stimulus, thus a classifier could not rely on independent information about motion and binocular disparity to distinguish these conjunctions. This study expands on evidence that disparity and motion interact at many levels of human visual processing, particularly within the dorsal stream. It also lends support to the idea that stereopsis is subserved by early mechanisms also tuned to direction of motion. PMID- 22323625 TI - Training in a ballistic task but not a visuomotor task increases responses to stimulation of human corticospinal axons. AB - Short periods of training in motor tasks can increase motor cortical excitability. This study investigated whether changes also occur at a subcortical level. Subjects trained in ballistic finger abduction or visuomotor tracking. The right index finger rotated around the metacarpophalangeal (MCP) joint in a splint. Surface EMG was recorded from the first dorsal interosseous. Transcranial magnetic stimulation over the back of the head (double-cone coil) elicited cervicomedullary motor evoked potentials (CMEPs) by stimulation of corticospinal axons. Responses were recorded from the relaxed muscle before, between, and after two sets of training. In study 1 (n = 7), training comprised two sets of 150 maximal finger abductions. Feedback of acceleration was provided. With training, acceleration increased significantly. CMEPs increased to 248 +/- 152% (+/- SD) of baseline immediately after training (P = 0.007) but returned to control level (155 +/- 141%) 10 min later. In study 2 (n = 7), subjects matched MCP joint angle to a target path on a computer screen. After ~30 min of training, tracking improved as shown by increased correlation between joint angle and the target pathway, reduced time lag, and reduced EMG(rms). However, CMEPs remained unchanged. These results show that transmission through the corticospinal pathway at a spinal level increased after repeated ballistic movements but not after training in a visuomotor task. Thus, changes at a spinal level may contribute to improved performance in some motor tasks. PMID- 22323626 TI - Task-dependent changes in cortical excitability and effective connectivity: a combined TMS-EEG study. AB - The brain's electrical response to transcranial magnetic stimulation (TMS) is known to be influenced by exogenous factors such as the frequency and intensity of stimulation and the orientation and positioning of the stimulating coil. Less understood, however, is the influence of endogenous neural factors, such as global brain state, on the TMS-evoked response (TMS-ER). In the present study, we explored how changes in behavioral state affect the TMS-ER by perturbing the superior parietal lobule (SPL) with single pulses of TMS and measuring consequent differences in the frequency, strength, and spatial spread of TMS-evoked currents during the delay period of a spatial short-term memory task and during a period of passive fixation. Results revealed that task performance increased the overall strength of electrical currents induced by TMS, increased the spatial spread of TMS-evoked activity to distal brain regions, and increased the ability of TMS to reset the phase of ongoing broadband cortical oscillations. By contrast, task performance had little effect on the dominant frequency of the TMS-ER, both locally and at distal brain areas. These findings contribute to a growing body of work using combined TMS and neuroimaging methods to explore task-dependent changes in the functional organization of cortical networks implicated in task performance. PMID- 22323627 TI - Neural mechanisms of rhythmic masking release in monkey primary auditory cortex: implications for models of auditory scene analysis. AB - The ability to detect and track relevant acoustic signals embedded in a background of other sounds is crucial for hearing in complex acoustic environments. This ability is exemplified by a perceptual phenomenon known as "rhythmic masking release" (RMR). To demonstrate RMR, a sequence of tones forming a target rhythm is intermingled with physically identical "Distracter" sounds that perceptually mask the rhythm. The rhythm can be "released from masking" by adding "Flanker" tones in adjacent frequency channels that are synchronous with the Distracters. RMR represents a special case of auditory stream segregation, whereby the target rhythm is perceptually segregated from the background of Distracters when they are accompanied by the synchronous Flankers. The neural basis of RMR is unknown. Previous studies suggest the involvement of primary auditory cortex (A1) in the perceptual organization of sound patterns. Here, we recorded neural responses to RMR sequences in A1 of awake monkeys in order to identify neural correlates and potential mechanisms of RMR. We also tested whether two current models of stream segregation, when applied to these responses, could account for the perceptual organization of RMR sequences. Results suggest a key role for suppression of Distracter-evoked responses by the simultaneous Flankers in the perceptual restoration of the target rhythm in RMR. Furthermore, predictions of stream segregation models paralleled the psychoacoustics of RMR in humans. These findings reinforce the view that preattentive or "primitive" aspects of auditory scene analysis may be explained by relatively basic neural mechanisms at the cortical level. PMID- 22323628 TI - Attentional selection of location and modality in vision and touch modulates low frequency activity in associated sensory cortices. AB - Selective attention allows us to focus on particular sensory modalities and locations. Relatively little is known about how attention to a sensory modality may relate to selection of other features, such as spatial location, in terms of brain oscillations, although it has been proposed that low-frequency modulation (alpha- and beta-bands) may be key. Here, we investigated how attention to space (left or right) and attention to modality (vision or touch) affect ongoing low frequency oscillatory brain activity over human sensory cortex. Magnetoencephalography was recorded while participants performed a visual or tactile task. In different blocks, touch or vision was task-relevant, whereas spatial attention was cued to the left or right on each trial. Attending to one or other modality suppressed alpha-oscillations over the corresponding sensory cortex. Spatial attention led to reduced alpha-oscillations over both sensorimotor and occipital cortex contralateral to the attended location in the cue-target interval, when either modality was task-relevant. Even modality selective sensors also showed spatial-attention effects for both modalities. The visual and sensorimotor results were generally highly convergent, yet, although attention effects in occipital cortex were dominant in the alpha-band, in sensorimotor cortex, these were also clearly present in the beta-band. These results extend previous findings that spatial attention can operate in a multimodal fashion and indicate that attention to space and modality both rely on similar mechanisms that modulate low-frequency oscillations. PMID- 22323629 TI - Anterior cingulate neurons in the rat map anticipated effort and reward to their associated action sequences. AB - Goal-directed behaviors require the consideration and expenditure of physical effort. The anterior cingulate cortex (ACC) appears to play an important role in evaluating effort and reward and in organizing goal-directed actions. Despite agreement regarding the involvement of the ACC in these processes, the way in which effort-, reward-, and motor-related information is registered by networks of ACC neurons is poorly understood. To contrast ACC responses to effort, reward, and motor behaviors, we trained rats on a reversal task in which the selected paths on a track determined the level of effort or reward. Effort was presented in the form of an obstacle that was climbed to obtain reward. We used single-unit recordings to identify neural correlates of effort- and reward-guided behaviors. During periods of outcome anticipation, 52% of recorded ACC neurons responded to the specific route taken to the reward while 21% responded prospectively to effort and 12% responded prospectively to reward. In addition, effort- and reward selective neurons typically responded to the route, suggesting that these cells integrated motor-related activity with expectations of future outcomes. Furthermore, the activity of ACC neurons did not discriminate between choice and forced trials or respond to a more generalized measure of outcome value. Nearly all neural responses to effort and reward occurred after path selection and were restricted to discrete temporal/spatial stages of the task. Together, these findings support a role for the ACC in integrating route-specific actions, effort, and reward in the service of sustaining discrete movements through an effortful series of goal-directed actions. PMID- 22323630 TI - Permeation properties of the hair cell mechanotransducer channel provide insight into its molecular structure. AB - Mechanoelectric transducer (MET) channels, located near stereocilia tips, are opened by deflecting the hair bundle of sensory hair cells. Defects in this process result in deafness. Despite this critical function, the molecular identity of MET channels remains a mystery. Inherent channel properties, particularly those associated with permeation, provide the backbone for the molecular identification of ion channels. Here, a novel channel rectification mechanism is identified, resulting in a reduced pore size at positive potentials. The apparent difference in pore dimensions results from Ca(2+) binding within the pore, occluding permeation. Driving force for permeation at hyperpolarized potentials is increased because Ca(2+) can more easily be removed from binding within the pore due to the presence of an electronegative external vestibule that dehydrates and concentrates permeating ions. Alterations in Ca(2+) binding may underlie tonotopic and Ca(2+)-dependent variations in channel conductance. This Ca(2+)-dependent rectification provides targets for identifying the molecular components of the MET channel. PMID- 22323631 TI - Development of orientation tuning in simple cells of primary visual cortex. AB - Orientation selectivity and its development are basic features of visual cortex. The original model of orientation selectivity proposes that elongated simple cell receptive fields are constructed from convergent input of an array of lateral geniculate nucleus neurons. However, orientation selectivity of simple cells in the visual cortex is generally greater than the linear contributions based on projections from spatial receptive field profiles. This implies that additional selectivity may arise from intracortical mechanisms. The hierarchical processing idea implies mainly linear connections, whereas cortical contributions are generally considered to be nonlinear. We have explored development of orientation selectivity in visual cortex with a focus on linear and nonlinear factors in a population of anesthetized 4-wk postnatal kittens and adult cats. Linear contributions are estimated from receptive field maps by which orientation tuning curves are generated and bandwidth is quantified. Nonlinear components are estimated as the magnitude of the power function relationship between responses measured from drifting sinusoidal gratings and those predicted from the spatial receptive field. Measured bandwidths for kittens are slightly larger than those in adults, whereas predicted bandwidths are substantially broader. These results suggest that relatively strong nonlinearities in early postnatal stages are substantially involved in the development of orientation tuning in visual cortex. PMID- 22323632 TI - Mapping pain activation and connectivity of the human habenula. AB - The habenula, located in the posterior thalamus, is implicated in a wide array of functions. Animal anatomical studies have indicated that the structure receives inputs from a number of brain regions (e.g., frontal areas, hypothalamic, basal ganglia) and sends efferent connections predominantly to the brain stem (e.g., periaqueductal gray, raphe, interpeduncular nucleus). The role of the habenula in pain and its anatomical connectivity are well-documented in animals but not in humans. In this study, for the first time, we show how high-field magnetic resonance imaging can be used to detect habenula activation to noxious heat. Functional maps revealed significant, localized, and bilateral habenula responses. During pain processing, functional connectivity analysis demonstrated significant functional correlations between the habenula and the periaqueductal gray and putamen. Probabilistic tractography was used to assess connectivity of afferent (e.g., putamen) and efferent (e.g., periaqueductal gray) pathways previously reported in animals. We believe that this study is the first report of habenula activation by experimental pain in humans. Since the habenula connects forebrain structures with brain stem structures, we suggest that the findings have important implications for understanding sensory and emotional processing in the brain during both acute and chronic pain. PMID- 22323633 TI - Activation of protein kinase A and C prevents recovery from persistent depolarization produced by oxygen and glucose deprivation in rat hippocampal neurons. AB - Intracellular recordings were made from rat hippocampal CA1 neurons in rat brain slice preparations to investigate whether cAMP-dependent protein kinase (PKA) and calcium/phospholipid-dependent protein kinase C (PKC) contribute to the membrane dysfunction induced by oxygen and glucose deprivation (OGD). Superfusion of oxygen- and glucose-deprived medium produced a rapid depolarization ~5 min after the onset of the superfusion. When oxygen and glucose were reintroduced immediately after the rapid depolarization, the membrane depolarized further (persistent depolarization) and reached 0 mV after 5 min from the reintroduction. The pretreatment of the slice preparation with PKA inhibitors, H-89 and Rp-cAMPS, and an adenylate cyclase inhibitor, SQ 22, 536, significantly restored the membrane toward the preexposure potential level after the reintroduction of oxygen and glucose in a concentration-dependent manner. On the other hand, a phospholipase C inhibitor, U73122, a PKC inhibitor, GF109203X, and a nonselective protein kinase inhibitor, staurosporine, also significantly restored the membrane after the reintroduction. Moreover, an inositol-1,4,5-triphosphate receptor antagonist, 2-aminoethyl diphenylborinate, and calmodulin inhibitors, trifluoperazine and W-7, significantly restored the membrane after the reintroduction, while neither an alpha-subunit-selective antagonist for stimulatory G protein, NF449, a Ca(2+)/calmodulin-dependent kinase II inhibitor, KN-62, nor a myosin light chain kinase inhibitor, ML-7, significantly restored the membrane after the reintroduction. These results suggest that the activation of PKA and/or PKC prevents the recovery from the persistent depolarization produced by OGD. The Ca(2+)/calmodulin-stimulated adenylate cyclase may contribute to the activation of PKA. PMID- 22323634 TI - Receptive field dimensionality increases from the auditory midbrain to cortex. AB - In the primary auditory cortex, spectrotemporal receptive fields (STRFs) are composed of multiple independent components that capture the processing of disparate stimulus aspects by any given neuron. The origin of these multidimensional stimulus filters in the central auditory system is unknown. To determine whether multicomponent STRFs emerge prior to the forebrain, we recorded from single neurons in the main obligatory station of the auditory midbrain, the inferior colliculus. By comparing results of different spike-triggered techniques, we found that the neural responses in the inferior colliculus can be accounted for by a single stimulus filter. This was observed for all temporal response patterns, from strongly phasic to tonic. Our results reveal that spectrotemporal stimulus encoding undergoes a fundamental transformation along the auditory neuraxis, with the emergence of multidimensional receptive fields beyond the auditory midbrain. PMID- 22323635 TI - Acetylcholine-evoked afterdischarge in Aplysia bag cell neurons. AB - A brief synaptic input to the bag cell neurons of Aplysia evokes a lengthy afterdischarge and the secretion of peptide hormones that trigger ovulation. The input transmitter is unknown, although prior work has shown that afterdischarges are prevented by strychnine. Because molluscan excitatory cholinergic synapses are blocked by strychnine, we tested the hypothesis that acetylcholine acts on an ionotropic receptor to initiate the afterdischarge. In cultured bag cell neurons, acetylcholine induced a short burst of action potentials followed by either return to near baseline or, like a true afterdischarge, transition to continuous firing. The current underlying the acetylcholine-induced depolarization was dose dependent, associated with increased membrane conductance, and sensitive to the nicotinic antagonists hexamethonium, mecamylamine, and alpha-conotoxin ImI. Whereas nicotine, choline, carbachol, and glycine did not mimic acetylcholine, tetramethylammonium did produce a similar current. Consistent with an ionotropic receptor, the response was not altered by intracellular dialysis with the G protein blocker guanosine 5'-(beta-thio)diphosphate. Recording from the intact bag cell neuron cluster showed acetylcholine to evoke prominent depolarization, which often led to extended bursting, but only in the presence of the acetylcholinesterase inhibitor neostigmine. Extracellular recording confirmed that exogenous acetylcholine caused genuine afterdischarges, which, as per those generated synaptically, rendered the cluster refractory to further stimulation. Finally, treatment with a combination of mecamylamine and alpha-conotoxin ImI blocked synaptically induced afterdischarges in the intact bag cell neuron cluster. Acetylcholine appears to elicit the afterdischarge through an ionotropic receptor. This represents an expedient means for transient stimulation to elicit prolonged firing in the absence of ongoing synaptic input. PMID- 22323636 TI - Bridging the gap: global disparity processing in the human visual cortex. AB - The human stereoscopic system is remarkable in its ability to utilize widely separated features as references to support fine depth discrimination. In a search for possible neural substrates of this ability, we recorded high-density EEG and used a distributed inverse technique to estimate population-level disparity responses in five regions of interest (ROIs): V1, V3A, hMT+, V4, and lateral occipital complex (LOC). The stimulus was a central modulating disk surrounded by a correlated "reference" annulus presented in the fixation plane. We varied a gap separating the disk from the annulus parametrically from 0 to 5.5 degrees as a test of long-range disparity integration. In the V1, LOC, and hMT+ ROIs, the responses with gaps >0.5 degrees were equal to those obtained in a control condition where the surround was composed of uncorrelated noise (no reference). By contrast, in the V4 and V3A ROIs, responses with gaps as large as 5.5 degrees were still significantly higher than the control. As a test of the spatial distribution of the disparity reference information, we manipulated the properties of the stimulus by placing noise between the center and the surround or throughout the surround. The V3A ROI was particularly sensitive to disparity noise between the center and annulus regions, suggesting an important contribution of disparity edge detectors in this ROI. PMID- 22323637 TI - Contribution of EAG to excitability and potassium currents in Drosophila larval motoneurons. AB - Diversity in the expression of K(+) channels among neurons allows a wide range of excitability, growth, and functional regulation. Ether-a-go-go (EAG), a voltage gated K(+) channel, was first characterized in Drosophila mutants by spontaneous firing in nerve terminals and enhanced neurotransmitter release. Although diverse functions have been ascribed to this protein, its role within neurons remains poorly understood. The aim of this study was to characterize the function of EAG in situ in Drosophila larval motoneurons. Whole cell patch-clamp recordings performed from the somata revealed a decrease in I(Av) and I(Kv) K(+) currents in eag mutants and with targeted eag RNAi expression. Spontaneous spike-like events were observed in eag mutants but absent in wild-type motoneurons. Thus our results provide evidence that EAG represents a unique K(+) channel contributing to multiple K(+) currents in motoneurons helping to regulate excitability, consistent with previous observations in the Drosophila larval muscle. PMID- 22323639 TI - Illuminating the glomerular filtration barrier, two photons at a time. PMID- 22323638 TI - Enhanced locomotor adaptation aftereffect in the "broken escalator" phenomenon using anodal tDCS. AB - The everyday experience of stepping onto a stationary escalator causes a stumble, despite our full awareness that the escalator is broken. In the laboratory, this "broken escalator" phenomenon is reproduced when subjects step onto an obviously stationary platform (AFTER trials) that was previously experienced as moving (MOVING trials) and attests to a process of motor adaptation. Given the critical role of M1 in upper limb motor adaptation and the potential for transcranial direct current stimulation (tDCS) to increase cortical excitability, we hypothesized that anodal tDCS over leg M1 and premotor cortices would increase the size and duration of the locomotor aftereffect. Thirty healthy volunteers received either sham or real tDCS (anodal bihemispheric tDCS; 2 mA for 15 min at rest) to induce excitatory effects over the primary motor and premotor cortex before walking onto the moving platform. The real tDCS group, compared with sham, displayed larger trunk sway and increased gait velocity in the first AFTER trial and a persistence of the trunk sway aftereffect into the second AFTER trial. We also used transcranial magnetic stimulation to probe changes in cortical leg excitability using different electrode montages and eyeblink conditioning, before and after tDCS, as well as simulating the current flow of tDCS on the human brain using a computational model of these different tDCS montages. Our data show that anodal tDCS induces excitability changes in lower limb motor cortex with resultant enhancement of locomotor adaptation aftereffects. These findings might encourage the use of tDCS over leg motor and premotor regions to improve locomotor control in patients with neurological gait disorders. PMID- 22323640 TI - Anti-LAMP-2 autoantibodies in ANCA-associated pauci-immune glomerulonephritis. PMID- 22323641 TI - Do we now have a prognostic biomarker for progressive diabetic nephropathy? PMID- 22323642 TI - Induction of IgA deposits and glomerulonephritis by IgA rheumatoid factor. PMID- 22323643 TI - High prevalence of autoantibodies to hLAMP-2 in anti-neutrophil cytoplasmic antibody-associated vasculitis. AB - The involvement of autoantibodies to human lysosome-associated membrane protein-2 (hLAMP-2) in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is controversial because of the absence of confirmatory data subsequent to the initial reports of their high prevalence in this disease. We characterized three assays for anti-hLAMP-2 antibodies: ELISA and Western blotting assays using unglycosylated recombinant hLAMP-2 expressed in Escherichia coli, and an indirect immunofluorescence assay using stably transfected ldlD cells that expressed glycosylated full-length hLAMP-2 on the plasma membrane. The assays detected autoantibodies to hLAMP-2 in human sera reproducibly and with comparable sensitivity and the assays gave the same results in 80.5% of the test panel of 40 selected positive and negative sera. In untreated patients at presentation, the frequencies of autoantibodies to LAMP-2 were 89%, 91%, and 80%, respectively, among three groups of patients with ANCA-associated vasculitis from Vienna, Austria (n=19); Groningen, the Netherlands (n=50) and Cambridge, United Kingdom (n=53). Prevalence of LAMP-2 autoantibodies was similar in both those with myeloperoxidase-ANCA and proteinase 3-ANCA. Furthermore, we detected LAMP-2 autoantibodies in two ANCA-negative patients. LAMP-2 autoantibodies rapidly became undetectable after the initiation of immunosuppressive treatment and frequently became detectable again during clinical relapse. We conclude that when robust assays are used, circulating autoantibodies to hLAMP-2 can be detected in most European patients with ANCA-associated vasculitis. Large-scale prospective studies are now needed to determine whether they are pathogenic or merely an epiphenomenon. PMID- 22323644 TI - Expression of heme oxygenase-1 in thick ascending loop of henle attenuates angiotensin II-dependent hypertension. AB - Kidney-specific induction of heme oxygenase-1 (HO-1) attenuates the development of angiotensin II (Ang II) -dependent hypertension, but the relative contribution of vascular versus tubular induction of HO-1 is unknown. To determine the specific contribution of thick ascending loop of Henle (TALH) -derived HO-1, we generated a transgenic mouse in which the uromodulin promoter controlled expression of human HO-1. Quantitative RT-PCR and confocal microscopy confirmed successful localization of the HO-1 transgene to TALH tubule segments. Medullary HO activity, but not cortical HO activity, was significantly higher in transgenic mice than control mice. Enhanced TALH HO-1 attenuated the hypertension induced by Ang II delivered by an osmotic minipump for 10 days (139 +/- 3 versus 153 +/-2 mmHg in the transgenic and control mice, respectively; P<0.05). The lower blood pressure in transgenic mice associated with a 60% decrease in medullary NKCC2 transporter expression determined by Western blot. Transgenic mice also exhibited a 36% decrease in ouabain-sensitive sodium reabsorption and a significantly attenuated response to furosemide in isolated TALH segments. In summary, these results show that increased levels of HO-1 in the TALH can lower blood pressure by a mechanism that may include alterations in NKCC2-dependent sodium reabsorption. PMID- 22323645 TI - Exercise training blunts oxidative stress in sickle cell trait carriers. AB - The aim of this study was to analyze the effects of exercise training on oxidative stress in sickle cell trait carriers. Plasma levels of oxidative stress [advanced oxidation protein products (AOPP), protein carbonyl, malondialdehyde (MDA), and nitrotyrosine], antioxidant markers [catalase, glutathione peroxidase (GPX), and superoxide dismutase (SOD)], and nitrite and nitrate (NOx) were assessed at baseline, immediately following a maximal exercise test (T(ex)), and during recovery (T(1h), T(2h), T(24h)) in trained (T: 8 h/wk minimum) and untrained (U: no regular physical activity) sickle cell trait (SCT) carriers or control (CON) subjects (T-SCT, n = 10; U-SCT, n = 8; T-CON, n = 11; and U-CON, n = 11; age: 23.5 +/- 2.2 yr). The trained subjects had higher SOD activities (7.6 +/- 5.4 vs. 5.2 +/- 2.1 U/ml, P = 0.016) and lower levels of AOPP (142 +/- 102 vs. 177 +/- 102 MUM, P = 0.028) and protein carbonyl (82.1 +/- 26.0 vs. 107.3 +/- 30.6 nm/ml, P = 0.010) than the untrained subjects in response to exercise. In response to exercise, U-SCT had a higher level of AOPP (224 +/- 130 vs. 174 +/- 121 MUM, P = 0.012), nitrotyrosine (127 +/- 29.1 vs.70.6 +/- 46.6 nM, P = 0.003), and protein carbonyl (114 +/- 34.0 vs. 86.9 +/- 26.8 nm/ml, P = 0.006) compared with T-SCT. T-SCT had a higher SOD activity (8.50 +/- 7.2 vs. 4.30 +/- 2.5 U/ml, P = 0.002) and NOx (28.8 +/- 11.4 vs. 14.6 +/- 7.0 MUmol.l(-1).min(-1), P = 0.003) in response to exercise than U-SCT. Our data indicate that the overall oxidative stress and nitric oxide response is improved in exercise-trained SCT carriers compared with their untrained counterparts. These results suggest that physical activity could be a viable method of controlling the oxidative stress. This could have a beneficial impact because of its involvement in endothelial dysfunction and subsequent vascular impairment in hemoglobin S carriers. PMID- 22323646 TI - Microparticle production, neutrophil activation, and intravascular bubbles following open-water SCUBA diving. AB - The goal of this study was to evaluate annexin V-positive microparticles (MPs) and neutrophil activation in humans following decompression from open-water SCUBA diving with the hypothesis that changes are related to intravascular bubble formation. Sixteen male volunteer divers followed a uniform profile of four daily SCUBA dives to 18 m of sea water for 47 min. Blood was obtained prior to and at 80 min following the first and fourth dives to evaluate the impact of repetitive diving, and intravascular bubbles were quantified by trans-thoracic echocardiography carried out at 20-min intervals for 2 h after each dive. MPs increased by 3.4-fold after each dive, neutrophil activation occurred as assessed by surface expression of myeloperoxidase and the CD18 component of beta(2) integrins, and there was an increased presence of the platelet-derived CD41 protein on the neutrophil surface indicating interactions with platelet membranes. Intravascular bubbles were detected in all divers. Surprisingly, significant inverse correlations were found among postdiving bubble scores and MPs, most consistently at 80 min or more after the dive on the fourth day. There were significant positive correlations between MPs and platelet-neutrophil interactions after the first dive and between platelet-neutrophil interactions and neutrophil activation documented as an elevation in beta(2)-integrin expression after the fourth dive. We conclude that MPs- and neutrophil-related events in humans are consistent with findings in an animal decompression model. Whether there are causal relationships among bubbles, MPs, platelet-neutrophil interactions, and neutrophil activation remains obscure and requires additional study. PMID- 22323647 TI - Severe hypoxia affects exercise performance independently of afferent feedback and peripheral fatigue. AB - To test the hypothesis that hypoxia centrally affects performance independently of afferent feedback and peripheral fatigue, we conducted two experiments under complete vascular occlusion of the exercising muscle under different systemic O(2) environmental conditions. In experiment 1, 12 subjects performed repeated submaximal isometric contractions of the elbow flexor to exhaustion (RCTE) with inspired O(2) fraction fixed at 9% (severe hypoxia, SevHyp), 14% (moderate hypoxia, ModHyp), 21% (normoxia, Norm), or 30% (hyperoxia, Hyper). The number of contractions (performance), muscle (biceps brachii), and prefrontal near-infrared spectroscopy (NIRS) parameters and high-frequency paired-pulse (PS100) evoked responses to electrical muscle stimulation were monitored. In experiment 2, 10 subjects performed another RCTE in SevHyp and Norm conditions in which the number of contractions, biceps brachii electromyography responses to electrical nerve stimulation (M wave), and transcranial magnetic stimulation responses (motor evoked potentials, MEP, and cortical silent period, CSP) were recorded. Performance during RCTE was significantly reduced by 10-15% in SevHyp (arterial O(2) saturation, SpO(2) = ~75%) compared with ModHyp (SpO(2) = ~90%) or Norm/Hyper (SpO(2) > 97%). Performance reduction in SevHyp occurred despite similar 1) metabolic (muscle NIRS parameters) and functional (changes in PS100 and M wave) muscle states and 2) MEP and CSP responses, suggesting comparable corticospinal excitability and spinal and cortical inhibition between SevHyp and Norm. It is concluded that, in SevHyp, performance and central drive can be altered independently of afferent feedback and peripheral fatigue. It is concluded that submaximal performance in SevHyp is partly reduced by a mechanism related directly to brain oxygenation. PMID- 22323648 TI - Effect of exercise training on nitric oxide and superoxide/H2O2 signaling pathways in collateral-dependent porcine coronary arterioles. AB - Endothelial nitric oxide (NO) synthase (NOS) has been shown to contribute to enhanced vascular function after exercise training. Recent studies have revealed that relatively low concentrations of reactive oxygen species can contribute to endothelium-dependent vasodilation under physiological conditions. We tested the hypothesis that exercise training enhances endothelial function via endothelium derived vasodilators, NO and superoxide/H(2)O(2), in the underlying setting of chronic coronary artery occlusion. An ameroid constrictor was placed around the proximal left circumflex coronary artery to induce gradual occlusion in Yucatan miniature swine. At 8 wk postoperatively, pigs were randomly assigned to sedentary (pen-confined) or exercise-training (treadmill-run: 5 days/wk for 14 wk) regimens. Exercise training significantly enhanced concentration-dependent, bradykinin-mediated dilation in cannulated collateral-dependent arterioles (~130 MUm diameter) compared with sedentary pigs. NOS inhibition reversed training enhanced dilation at low bradykinin concentrations in collateral-dependent arterioles, although increased dilation persisted at higher bradykinin concentrations. Total and phosphorylated (Ser(1179)) endothelial NOS protein levels were significantly increased in arterioles from collateral-dependent compared with the nonoccluded region, independent of exercise. The H(2)O(2) scavenger polyethylene glycol-catalase abolished the training-enhanced bradykinin mediated dilation in collateral-dependent arterioles; similar results were observed with the SOD inhibitor diethyldithiocarbamate. Fluorescence measures of bradykinin-stimulated H(2)O(2) levels were significantly increased by exercise training, independent of occlusion. The NADPH inhibitor apocynin significantly attenuated bradykinin-mediated dilation in arterioles of exercise-trained, but not sedentary, pigs and was associated with significantly increased protein levels of the NADPH subunit p67phox. These data provide evidence that, in addition to NO, the superoxide/H(2)O(2) signaling pathway significantly contributes to exercise training-enhanced endothelium-mediated dilation in collateral-dependent coronary arterioles. PMID- 22323649 TI - Coronary collaterals provide a constant scaffold effect on the left ventricle and limit ischemic left ventricular dysfunction in humans. AB - Coronary collaterals preserve left ventricular (LV) function during coronary occlusion by reducing myocardial ischemia and may directly influence LV compliance. We aimed to re-evaluate the relationship between coronary collaterals, measured quantitatively with a pressure wire, and simultaneously recorded LV contractility from conductance catheter data during percutaneous coronary intervention (PCI) in humans. Twenty-five patients with normal LV function awaiting PCI were recruited. Pressure-derived collateral flow index (CFI(p)): CFI(p) = (P(w) - P(v))/(P(a) - P(v)) was calculated from pressure distal to coronary balloon occlusion (P(w)), central venous pressure (P(v)), and aortic pressure (P(a)). CFI(p) was compared with the changes in simultaneously recorded LV end-diastolic pressure (DeltaLVEDP), end-diastolic volume, maximum rate of rise in pressure (DeltaLVdP/dt(max); systolic function), and time constant of isovolumic relaxation (DeltaLV tau; diastolic function), measured by a LV cavity conductance catheter. Measurements were recorded at baseline and following a 1-min coronary occlusion and were duplicated after a 30-min recovery period. There was significant LV diastolic dysfunction following coronary occlusion (DeltaLVEDP: +24.5%, P < 0.0001; and DeltaLV tau: +20.0%, P < 0.0001), which inversely correlated with CFI(p) (DeltaLVEDP vs. CFI(p): r = -0.54, P < 0.0001; DeltaLV tau vs. CFI(p): r = -0.46, P = 0.0009). Subjects with fewer collaterals had lower LVEDP at baseline (r = 0.33, P = 0.02). CFI(p) was inversely related to the coronary stenosis pressure gradient at rest (r = -0.31, P = 0.03). Collaterals exert a direct hemodynamic effect on the ventricle and attenuate ischemic LV diastolic dysfunction during coronary occlusion. Vessels with lesions of greater hemodynamic significance have better collateral supply. PMID- 22323650 TI - Modified iodine-paper technique for the standardized determination of sweat gland activation. AB - Quantifying sweat gland activation provides important information when explaining differences in sweat rate between populations and physiological conditions. However, no standard technique has been proposed to measure sweat gland activation, while the reliability of sweat gland activation measurements is unknown. We examined the interrater and internal reliability of the modified iodine paper technique, as well as compared computer-aided analysis to manual counts of sweat gland activation. Iodine-impregnated paper was pressed against the skin of 35 participants in whom sweating was elicited by exercise in the heat or infusion of methylcholine. The number of active glands was subsequently determined by computer-aided analysis. In total, 382 measurements were used to evaluate: 1) agreement between computer analysis and manual counts; 2) the interrater reliability of computer analysis between independent investigators; and 3) the internal reliability of sweat gland activation measurements between duplicate samples. The number of glands identified with computer analysis did not differ from manual counts (68 +/- 29 vs. 72 +/- 24 glands/cm(2); P = 0.27). These measures were highly correlated (r = 0.77) with a mean bias +/- limits of agreement of -4 +/- 38 glands/cm(2). When comparing computer analysis measures between investigators, values were highly correlated (r = 0.95; P < 0.001) and the mean bias +/- limits of agreement was 4 +/- 18 glands/cm(2). Finally, duplicate measures of sweat gland activation were highly correlated (r = 0.88; P < 0.001) with a mean bias +/- limits of agreement of 3 +/- 29 glands/cm(2). These results favor the use of the modified-iodine paper technique with computer-aided analysis as a standard technique to reliably evaluate the number of active sweat glands. PMID- 22323651 TI - Mechanism of the lung-deflating action of the canine diaphragm at extreme lung inflation. AB - When lung volume in animals is passively increased beyond total lung capacity (TLC; transrespiratory pressure = +30 cmH(2)O), stimulation of the phrenic nerves causes a rise, rather than a fall, in pleural pressure. It has been suggested that this was the result of inward displacement of the lower ribs, but the mechanism is uncertain. In the present study, radiopaque markers were attached to muscle bundles in the midcostal region of the diaphragm and to the tenth rib pair in five dogs, and computed tomography was used to measure the displacement, length, and configuration of the muscle and the displacement of the lower ribs during relaxation at seven different lung volumes up to +60 cmH(2)O transrespiratory pressure and during phrenic nerve stimulation at the same lung volumes. The data showed that 1) during phrenic nerve stimulation at 60 cmH(2)O, airway opening pressure increased by 1.5 +/- 0.7 cmH(2)O; 2) the dome of the diaphragm and the lower ribs were essentially stationary during such stimulation, but the muscle fibers still shortened significantly; 3) with passive inflation beyond TLC, an area with a cranial concavity appeared at the periphery of the costal portion of the diaphragm, forming a groove along the ventral third of the rib cage; and 4) this area decreased markedly in size or disappeared during phrenic stimulation. It is concluded that the lung-deflating action of the isolated diaphragm beyond TLC is primarily related to the invaginations in the muscle caused by the acute margins of the lower lung lobes. These findings also suggest that the inspiratory inward displacement of the lower ribs commonly observed in patients with emphysema (Hoover's sign) requires not only a marked hyperinflation but also a large fall in pleural pressure. PMID- 22323652 TI - Endothelial leptin receptor mutation provides partial resistance to diet-induced obesity. AB - Leptin, a polypeptide hormone produced mainly by adipocytes, has diverse effects in both the brain and peripheral organs, including suppression of feeding. Other than mediating leptin transport across the blood-brain barrier, the role of the endothelial leptin receptor remains unclear. We recently generated a mutant mouse strain lacking endothelial leptin receptor signaling, and showed that there is an increased uptake of leptin by brain parenchyma after its delivery by in situ brain perfusion. Here, we tested the hypothesis that endothelial leptin receptor mutation confers partial resistance to diet-induced obesity. These ELKO mice had similar body weight and percent fat as their wild-type littermates when fed with rodent chow, but blood concentrations of leptin were significantly elevated. In response to a high-fat diet, wild-type mice had a greater gain of body weight and fat than ELKO mice. As shown by metabolic chamber measurement, the ELKO mice had higher oxygen consumption, carbon dioxide production, and heat dissipation, although food intake was similar to that of the wild-type mice and locomotor activity was even reduced. This indicates that the partial resistance to diet induced obesity was mediated by higher metabolic activity in the ELKO mice. Since neuronal leptin receptor knockout mice show obesity and diabetes, the results suggest that endothelial leptin signaling shows opposite effects from that of neuronal leptin signaling, with a facilitatory role in diet-induced obesity. PMID- 22323653 TI - Why did Grandpa drop the glass? PMID- 22323654 TI - Neuroprotective role of the TREK-1 channel in decompression sickness. AB - Nitrogen supersaturation and bubble formation can occur in the vascular system after diving, leading to death and nervous disorders from decompression sickness (DCS). Bubbles alter the vascular endothelium, activate platelets, and lead to focal ischemia with neurological damage mediated by the mechanosensitive TREK-1 neuronal potassium ion channel that sets pre- and postsynaptic resting membrane potentials. We report a neuroprotective effect associated with TREK-1. C57Bl6 mice were subjected to decompression from a simulated 90 msw dive. Of 143 mice that were wild type (WT) for TREK-1, 51.7% showed no DCS, 27.3% failed a grip test, and 21.0% died. Of 88 TREK-1 knockouts (KO), 26.1% showed no DCS, 42.0% failed a grip test, and 31.8% died. Mice that did not express TREK-1 had lower DCS resistance and were more likely to develop neurological symptoms. We conclude that the TREK-1 potassium channel was neuroprotective for DCS. PMID- 22323655 TI - Do PTK2 gene polymorphisms contribute to the interindividual variability in muscle strength and the response to resistance training? A preliminary report. AB - The protein tyrosine kinase-2 (PTK2) gene encodes focal adhesion kinase, a structural protein involved in lateral transmission of muscle fiber force. We investigated whether single-nucleotide polymorphisms (SNPs) of the PTK2 gene were associated with various indexes of human skeletal muscle strength and the interindividual variability in the strength responses to resistance training. We determined unilateral knee extension single repetition maximum (1-RM), maximum isometric voluntary contraction (MVC) knee joint torque, and quadriceps femoris muscle specific force (maximum force per unit physiological cross-sectional area) before and after 9 wk of knee extension resistance training in 51 untrained young men. All participants were genotyped for the PTK2 intronic rs7843014 A/C and 3' untranslated region (UTR) rs7460 A/T SNPs. There were no genotype associations with baseline measures or posttraining changes in 1-RM or MVC. Although the training-induced increase in specific force was similar for all PTK2 genotypes, baseline specific force was higher in PTK2 rs7843014 AA and rs7460 TT homozygotes than in the respective rs7843014 C- (P = 0.016) and rs7460 A-allele (P = 0.009) carriers. These associations between muscle specific force and PTK2 SNPs suggest that interindividual differences exist in the way force is transmitted from the muscle fibers to the tendon. Therefore, our results demonstrate for the first time the impact of genetic variation on the intrinsic strength of human skeletal muscle. PMID- 22323656 TI - Effects of recombinant human keratinocyte growth factor on surfactant, plasma, and liver phospholipid homeostasis in hyperoxic neonatal rats. AB - Respiratory distress and bronchopulmonary dysplasia (BPD) are major problems in preterm infants that are often addressed by glucocorticoid treatment and increased oxygen supply, causing catabolic and injurious side effects. Recombinant human keratinocyte growth factor (rhKGF) is noncatabolic and antiapoptotic and increases surfactant pools in immature lungs. Despite its usefulness in injured neonatal lungs, the mechanisms of improved surfactant homeostasis in vivo and systemic effects on lipid homeostasis are unknown. We therefore exposed newborn rats to 85% vs. 21% oxygen and treated them systemically with rhKGF for 48 h before death at 7 days. We determined type II pneumocyte (PN-II) proliferation, surfactant protein (SP) mRNA expression, and the pulmonary metabolism of individual phosphatidylcholine (PC) species using [D(9)-methyl]choline and tandem mass spectrometry. In addition, we assessed liver and plasma lipid metabolism, addressing PC synthesis de novo, the liver-specific phosphatidylethanolamine methyl transferase (PEMT) pathway, and triglyceride concentrations. rhKGF was found to maintain PN-II proliferation and increased SP B/C expression and surfactant PC in both normoxic and hyperoxic lungs. We found increased total PC together with decreased [D(9)-methyl]choline enrichment, suggesting decreased turnover rather than increased secretion and synthesis as the underlying mechanism. In the liver, rhKGF increased PC synthesis, both de novo and via PEMT, underlining the organotypic differences of rhKGF actions on lipid metabolism. rhKGF increased the hepatic secretion of newly synthesized polyunsaturated PC, indicating improved systemic supply with choline and essential fatty acids. We suggest that rhKGF has potential as a therapeutic agent in neonates by improving pulmonary and systemic PC homeostasis. PMID- 22323657 TI - Influence of housing conditions from weaning to adulthood on the ventilatory, thermoregulatory, and endocrine responses to hypoxia of adult female rats. AB - Housing conditions affect animal physiology. We previously showed that the hypoxic ventilatory and thermoregulatory responses to hypoxia of adult male rats housed in triads during the juvenile period (postnatal day 21 to adulthood) were significantly reduced compared with animals housed in pairs. Because sex hormones influence development and responsiveness to environmental stressors, this study investigated the impact of housing on the respiratory and thermoregulatory physiology of female rats. Since neonatal stress attenuates the hypoxic ventilatory response (HVR) of female rats at adulthood, experiments were performed both on "control" (undisturbed) animals and rats subjected to neonatal maternal separation (NMS; 3 h/day, postnatal days 3-12). At adulthood, ventilatory activity was measured by whole body plethysmography under normoxic and hypoxic conditions [fraction of inspired oxygen (Fi(O(2))) = 0.12; 20 min]. The ventilatory and body temperature responses to hypoxia of female rats raised in triads were reduced compared with rats housed in pairs. Housing female rats in triads did not affect basal or hypoxic plasma corticosterone levels but did increase levels of estradiol significantly. We conclude that modest changes in housing conditions (pairs vs. triads) from weaning to adulthood does influence basic homeostatic functions such as temperature and respiratory regulation. Triad housing can reverse the manifestations of respiratory instability at adulthood induced by stressful neonatal treatments. This should raise awareness of the benefits of increasing social interactions in clinical settings but also caution researchers of the potential impact of such subtle changes on experimental protocols and interpretation of results. PMID- 22323658 TI - Role of Rab family GTPases and their effectors in melanosomal logistics. AB - Rab GTPases constitute a family of small GTPases that regulate a variety of membrane trafficking events in all eukaryotic cells by recruiting their specific effector molecules. Recent accumulating evidence indicates that members of the mammalian Rab small GTPase family are involved in certain physiological and pathological processes. In particular, functional impairments of specific Rab proteins, e.g. Rab38 and Rab27A, their regulators or their effectors cause pigmentation disorders in humans and coat colour variations in mice because such impairments cause defects in melanosomal logistics, i.e. defects in melanosome biogenesis and transport. Genetic and biochemical analyses of the gene products responsible for mammalian pigmentation disorders in the past decade have revealed that Rab-mediated endosomal transport systems and melanosome transport systems play crucial roles in the efficient darkening of mammalian hair and skin. In this article, we review current knowledge regarding melanosomal logistics, with particular focus on the roles of Rab small GTPases and their effectors. PMID- 22323659 TI - A bioassay experience and lessons learned on the internal contamination of (131)I during a maintenance period in a Korean nuclear power plant. AB - During a maintenance period at a Korean nuclear power plant, internal exposure of radiation workers occurred by the inhalation of (131)I that was released into the reactor building from a primary system opening due to defective fuels. The internal activity in radiation workers contaminated by (131)I was immediately measured using a whole body counter (WBC). A whole body counting was performed again a few days later, considering the factors of equilibrium in the body. The intake and the committed effective dose were estimated based on the WBC results. The intake was also calculated by hand, based on both the entrance records to the reactor building, and the counted results of the air concentration for (131)I were compared with the whole body counting results. PMID- 22323660 TI - Low hydrogen sulphide and chronic kidney disease: a dangerous liaison. AB - Hydrogen sulphide, H(2)S, is a gaseous compound involved in a number of biological responses, e.g. blood pressure, vascular function and energy metabolism. In particular, H(2)S is able to lower blood pressure, protect from injury in models of ischaemia-reperfusion and induce a hypometabolic state. In chronic kidney disease (CKD), low plasma hydrogen sulphide levels have been established in humans and in animal models. The enzymes involved in its production are cystathionine beta-synthase, cystathionine gamma-lyase and 3 mercaptopyruvate sulphurtransferase. The mechanisms for H(2)S decrease in CKD are related to the reduced gene expression (demonstrated in uraemic patient blood cells) and decreased protein levels (in tissues such as liver, kidney, brain in a CKD rat model). In the present Nephrol Dial Transplant issue, in fact, Aminzadeh and Vaziri document that the alterations in this pathway complicate the uraemic state and are linked to CKD progression. They furnish a time frame in CKD and record enzyme tissue distribution. It remains to be established if low H(2)S is causally linked to CKD progression and if interventions aimed to restore the status quo ante are able to modify this picture. PMID- 22323661 TI - Comparison of high sensitivity and contemporary troponin I immunoassays for the early detection of acute myocardial infarction in the emergency department. PMID- 22323662 TI - Establishment of a reference interval for urinary neutrophil gelatinase associated lipocalin. AB - INTRODUCTION: Neutrophil gelatinase-associated lipocalin (NGAL) is emerging as a promising new biomarker for the early identification of acute kidney injury (AKI). We have determined a reference range in a large healthy population. In addition, as NGAL is a neutrophil-related protein, we investigated whether the presence of leukocyturia has the potential to significantly alter the specificity of NGAL in the diagnosis of AKI. METHODS: One hundred and seventy-four subjects (100 men, 74 women ranging from 19 to 88 y) were included in the reference population. Urinary NGAL was analysed on the Abbott ARCHITECT and results expressed in mass (MUg/L) and also normalized to urinary creatinine (MUg/mmol). Fifty-two leukocyturic urine samples were also analysed for NGAL. RESULTS: The 95th centile for NGAL was determined to be 107 MUg/L (13 MUg/mmol). There were significant gender-related differences for NGAL, with women having higher concentrations. There were significant age-related differences for NGAL between the 40-59 and 60-88 y age categories. There were significant age-related differences between the <40 and 60-88 y categories when NGAL was normalized to creatinine. In addition, we found significantly higher concentrations of NGAL in leukocyturia (P < 0.0001). CONCLUSIONS: We have established a 95th centile cut off for urinary NGAL in a reference population. We have demonstrated the important potential interference of leukocyturia in confounding the interpretation of NGAL in the diagnosis of AKI. PMID- 22323664 TI - Routine pre-procedure laboratory testing for patients undergoing outpatient cerebral angiography is not indicated. AB - BACKGROUND: Cerebral angiography is a routine low-risk procedure. Laboratory testing is performed in almost all patients. Some testing may be warranted in selected patients but can also result in delays in performing the procedure. PURPOSE: To determine if routine pre-procedure testing for outpatient cerebral angiography is necessary. METHODS: 447 patients who underwent outpatient cerebral angiography were reviewed. The tests were evaluated for any abnormality, correlation of the abnormality with underlying diseases and for any impact that these tests may have on the safety of the procedure. Only tests performed at our institution were analyzed. All instances of any hospital/physician visit related to the procedure were recorded. RESULTS: A low hemoglobin, hematocrit and platelet count was seen in 3.5%, 1.8% and 0.1% of patients, respectively. These were marginally outside the reference range and not sufficiently abnormal to indicate underlying disease or to affect the procedure. An elevated prothrombin time/international normalized ratio was seen in 4.5% of patients and this was associated with warfarin use (p<0.0001). About 15% of the patients had a disturbance in renal function. An elevated creatinine was associated with diabetes (OR 3.2, 95% CI 1.8 to 5.7, p=0.0001) and hypertension (OR 4.4, 95% CI 2.1 to 9.2, p<0.0001). Cerebral angiography was performed on these patients with appropriate renal protective measures and no cases of acute renal failure secondary to contrast administration were documented. CONCLUSION: The incidence of abnormal testing in patients undergoing outpatient cerebral angiography is very low. These results and evidence in the literature suggest that the majority of patients undergoing cerebral angiography do not require any pre-procedure testing. Assessment of renal function using the estimated glomerular filtration rate in high-risk patients only is, however, warranted. PMID- 22323663 TI - Phase I study of terameprocol in patients with recurrent high-grade glioma. AB - Terameprocol is a global transcription inhibitor that affects cell division apoptosis, drug resistance, hypoxia responsive genes, and radiation resistance in hypoxia. A multicenter, dose-escalation study was conducted in heavily pretreated patients with recurrent, measurable, high-grade gliomas. Terameprocol was administered intravenously for 5 consecutive days each month and discontinued for toxicity or progression. Patients taking enzyme-inducing antiseizure drugs (EIASDs) were escalated independently. Thirty-five patients with a median Karnofsky performance status of 80, median age of 46 years, and median of 2 prior treatment regimens were accrued. Doses of 750, 1100, 1700, and 2200 mg/day were administered. Terameprocol was reformulated to avoid acidosis related to the excipient and was well tolerated at 1700 mg/day. Hypoxia and interstitial nephritis were noted at 2200 mg/day. Concurrent administration of EIASD did not significantly affect the serum pharmacokinetics of the terameprocol. Although no responses were seen, stable disease was noted in 9 (28%) of 32 evaluable patients, with 5 (13%) continuing treatment for >6 months (>=6, 8, 10, 10, and >=21 months). The overall median survival was 5.9 months. This phase I study defined the toxicity of terameprocol, determined that EIASDs do not affect its pharmacokinetics, and identified 1700 mg/day as the dose for future studies. Preclinical and human data suggest that this novel transcription inhibitor is worthy of further study. The long-term stability noted in some patients and the lack of associated myelosuppression suggest that terameprocol could be safely combined with radiation and temozolomide in newly diagnosed high-grade gliomas. PMID- 22323665 TI - Assessing the relationship between volume and outcome in hospital services: implications for service centralization. AB - Proposals for centralizing services are often justified on the basis of studies linking the volume of activity to the outcomes achieved. However, the evidence of such studies is far from demonstrating a causal link between volume and outcome. This article assesses the main reasons why volume and outcome studies do not in themselves demonstrate a causal link, and therefore do not provide adequate support for proposals for centralizing hospital services. It then sets out a number of precepts to guide those responsible for proposing centralization of services. PMID- 22323666 TI - The organizational stress measure: an integrated methodology for assessing job stress and targeting organizational interventions. AB - This paper briefly describes the OSM (Organizational Stress Measure) which was developed over a decade ago and has evolved to become a well-established practical method not only for assessing wellbeing at work but also as a cost effective strategy to tackle workplace stress. The OSM measures perceived organizational pressures and felt individual strains within the same instrument, and provides a rich and subtle picture of both the organizational culture and the personal perspectives of the constituent staff groups. There are many types of organizational pressure that may impact upon the wellbeing and potential effectiveness of staff including skill shortages, ineffective strategic planning and poor leadership, and these frequently result in reduced performance, absenteeism, high turnover and poor staff morale. These pressures may increase the probability of some staff reacting negatively and research with the OSM has shown that increased levels of strain for small clusters of staff may be a leading indicator of future organizational problems. One of the main benefits of using the OSM is the ability to identify 'hot-spots', where organizational pressures are triggering high levels of personal strain in susceptible clusters of staff. In this way, the OSM may act as an 'early warning alarm' for potential organizational problems. PMID- 22323667 TI - Safety subcultures in health-care organizations and managing medical error. AB - Leadership has been proposed as a key latent factor influencing the safety culture of an organization, the likelihood of errors occurring and the way in which these are managed. Therefore, when an error occurs, managers have an integral role to ensure that the most desirable outcomes are achieved for patients, health-care staff and their organization. Semistructured interviews were conducted in a large UK teaching hospital to explore the perspectives of staff who are tasked in some way with managing patient safety. Data from 26 transcripts were analysed using an adapted version of Spencer's (2003) qualitative framework, which revealed five primary themes. This paper reports findings from two overarching primary themes, described as being management and safety subcultures. These themes describe experiences of managing medical errors and the subgroup variations between professions, ranks and specialties in attitudes and behaviours towards error, and its management in a large National Health Service Trust. We discuss implications for health-care managers and health professionals in developing a stronger and more unified safety culture in their organizations, along with considerations for academic researchers when undertaking health services research. PMID- 22323668 TI - Public violence, staff harassment and the wellbeing of nursing staff: an analysis of national survey data. AB - Instances of physical violence from members of the public and non-physical harassment from colleagues are highly prevalent in the health-care workforce and can be damaging to both staff and patients. While policy has tended to focus on the more visible problem of public violence, little is known about which of the two behaviours is the most damaging. This study compared the consequences of public violence and staff harassment for wellbeing in two large samples of English nurses. The results revealed that while both types of aggression were related to decreased levels of staff wellbeing, staff harassment had a stronger negative association with wellbeing than public violence. The relationships between each of the types of aggression and some aspects of wellbeing were moderated by perceived supervisory support, such that the negative effects on wellbeing were greater for those with higher levels of support. The major implication of this study is that health-care organizations must pay more attention to the prevention of staff harassment in the workplace. PMID- 22323669 TI - The effects on length of stay of introducing a fast track patient pathway for myocardial infarction: a before and after evaluation. AB - The aim was to assess whether the implementation of a fast-track patient pathway (FTPP) at an invasive treatment ward (ITW) could reduce the length of hospital stay (LOHS), among patients with non-ST Elevation Myocardial Infarction (NSTEMI). A before-and-after study was carried out, based on historical data from a total of 202 patients with NSTEMI admitted to a coronary ITW during two inclusion periods each lasting 100 days (Period I, 2004, no fast track, 95 consecutive patients; Period II, 2005, fast track implemented, 107 consecutive patients). Patients were followed during 180 days as concerns the total LOHS. A total of 33 patients passed through the FTPP. Their mean total LOHS was significantly shorter (3.3 days reduction; 95% CI 1.7, 5.5 days) as compared with all Period II patients. In total, Period II patients, however, spent significantly more days (mean, 1.7 days more; 95% CI 0.2, 3.3 days) in hospital than Period I patients. Thus, the implementation of FTPP reduced the mean LOHS for patients selected for the FTPP, but the mean LOHS for other patients rose and so the overall mean LOHS turned out to be significantly prolonged. The implementation of FTPP appears a complicated matter; changing one component has consequences for the wider health care system. PMID- 22323670 TI - Changing organizational structure and organizational memory in primary care practices: a qualitative interview study. AB - Organizational structure is built through dynamic processes which blend historical force and management decisions, as a part of a broader process of constructing organizational memory (OM). OM is considered to be one of the main competences leading to the organization's success. This study focuses on the impact of the Quality and Outcome Framework (QOF), which is a Pay-for-Performance scheme, on general practitioner (GP) practices in the UK. The study is based on semistructured interviews with four GP practices in the north of England involving 39 informants. The findings show that the way practices assigned different functions into specialized units, divisions or departments shows the degree of specialization in their organizational structures. More specialized unit arrangements, such as an IT division, particular chronic disease clinics or competence-based job distributions enhanced procedural memory development through enabling regular use of knowledge in specific context, which led to competence building. In turn, such competence at particular functions or jobs made it possible for the practices to achieve their goals more efficiently. This study concludes that organizational structure contributed strongly to the enhancement of OM, which in turn led to better organizational competence. PMID- 22323671 TI - Strategies for dealing with future shortages in the nursing workforce: a review. AB - The well-anticipated and well-documented demographic shift attributed to ageing of the baby boomer generation will place significant demands upon the health-care industry in the future. Significant resources such as the nurse workforce, will be needed to provide health-care services to this cohort. There is a looming shortage of professional and paraprofessional nurses. This paper evaluates strategies that can be utilized to decrease the rate of the nursing shortage, while retaining the current supply of nurses. Recommendations for solving the nursing shortage problem include enhancing the work environment through fostering open communication, improving technology, nurse empowerment, building long lasting and fulfilling partnerships, and efficient workplace organization. PMID- 22323672 TI - Workforce issues in European Union health policy. PMID- 22323673 TI - Impact of increased patient choice of providers in Sweden: cataract surgery. AB - OBJECTIVES: Choice of provider was introduced in Sweden in 2001. Our aim was to describe the scope and character of patient flows and to analyze any differences between patients who chose to move outside of their home county (movers) and those who did not (non-movers) with regard to age, sex, waiting time and level of need. METHODS: Use of cataract operations between 2005 and 2008 based on data from the National Cataract Register. Data were analysed using descriptive statistics, odds ratios and multivariate regression analysis to compare movers and non-movers. Information on contracting between county councils and providers in other counties was obtained from a survey. RESULTS: Only 4% of cataract patients were treated by a provider outside their home county. Patient flows were mainly determined by contracts between county councils and providers, and only 1% were considered to be 'true' movers (i.e. patients who were not part of any special contracting agreement). Movers differed from non-movers in that they were on average younger, had less serious visual problems and had shorter waiting times. CONCLUSION: Though patient flows are minor in scope, the possibility of changing provider has probably been important in tackling long waits in some counties. However, the reform may threaten the equity of health care use. PMID- 22323674 TI - Postmenopausal vaginal bleeding in women using hormone replacement therapy. AB - OBJECTIVE: To estimate the risk of endometrial cancer in postmenopausal women presenting with vaginal bleeding using estrogen-progestogen hormone replacement therapy (HRT) regimens and to assess if the duration of HRT use has an effect on the risk of diagnosing endometrial cancer. STUDY DESIGN: Cross-sectional study of consecutive women presenting with postmenopausal vaginal bleeding at a gynaecological oncology centre in the UK. Main outcome measures Endometrial cancer diagnosis. RESULTS: Over a 62-month period, 4847 women were investigated for postmenopausal vaginal bleeding. The majority of women (4097, 84.5%) did not use any HRT preparation at the time of initial referral and 750 (15.5%) women were using combined HRT preparations. A total of 298 (6.1%) women were diagnosed with endometrial carcinoma. Women using HRT preparations were significantly less likely to be diagnosed with endometrial cancer compared with women not using HRT (adjusted odds ratio = 0.229, 95% CI 0.116-0.452; P < 0.0001). The longer duration of HRT use did increase the risk of diagnosing endometrial cancer in women presenting with postmenopausal vaginal bleeding, but this was not statistically significant. CONCLUSIONS: Postmenopausal women presenting with vaginal bleeding and using combined HRT preparations have significantly lower risk of being diagnosed with endometrial cancer when compared with women not using HRT. PMID- 22323675 TI - Taking back the brain: could neurofeedback training be effective for relieving distressing auditory verbal hallucinations in patients with schizophrenia? AB - Progress in identifying the neural correlates of auditory verbal hallucinations (AVHs) experienced by patients with schizophrenia has not fulfilled its promise to lead to new methods of treatments. Given the existence of a large number of such patients who have AVHs that are refractory to traditional treatments, there is the urgent need for the development of new effective interventions. This article proposes that the technique of neurofeedback may be an appropriate method to allow the translation of pure research findings from AVH-research into a clinical intervention. Neurofeedback is a method through which individuals can self-regulate their neural activity in specific neural regions/frequencies, following operant conditioning of their intentional manipulation of visually presented real-time feedback of their neural activity. Four empirically testable hypotheses are proposed as to how neurofeedback may be employed to therapeutic effect in patients with AVHs. PMID- 22323676 TI - Groin pain after replacement of the hip: aetiology, evaluation and treatment. AB - Persistent groin pain after seemingly successful total hip replacement (THR) appears to have become more common. Recent studies have indicated a high incidence after metal-on-polyethylene and metal-on-metal conventional THR and it has been documented in up to 18% of patients after metal-on-metal resurfacing. There are many causes, including acetabular loosening, stress fracture, and iliopsoas tendonitis and impingement. The evaluation of this problem requires a careful history and examination, plain radiographs and an algorithmic approach to special diagnostic imaging and tests. Non-operative treatment is not usually successful. Specific operative treatment depending on the cause of the pain usually involves revision of the acetabular component, iliopsoas tenotomy or other procedures, and is usually successful. Here, an appropriate algorithm is described. PMID- 22323677 TI - Conservative management of patients with an osteoporotic vertebral fracture: a review of the literature. AB - Osteoporotic vertebral compression fractures (VCFs) are an increasing public health problem. Recently, randomised controlled trials on the use of kyphoplasty and vertebroplasty in the treatment of these fractures have been published, but no definitive conclusions have been reached on the role of these interventions. The major problem encountered when trying to perform a meta-analysis of the available studies for the use of cementoplasty in patients with a VCF is that conservative management has not been standardised. Forms of conservative treatment commonly used in these patients include bed rest, analgesic medication, physiotherapy and bracing. In this review, we report the best evidence available on the conservative care of patients with osteoporotic VCFs and associated back pain, focusing on the role of the most commonly used spinal orthoses. Although orthoses are used for the management of these patients, to date, there has been only one randomised controlled trial published evaluating their value. Until the best conservative management for patients with VCFs is defined and standardised, no conclusions can be drawn on the superiority or otherwise of cementoplasty techniques over conservative management. PMID- 22323678 TI - Porous metal revision shells for management of contained acetabular bone defects at a mean follow-up of six years: a comparison between up to 50% bleeding host bone contact and more than 50% contact. AB - We report the use of porous metal acetabular revision shells in the treatment of contained bone loss. The outcomes of 53 patients with <= 50% acetabular bleeding host bone contact were compared with a control group of 49 patients with > 50% to 85% bleeding host bone contact. All patients were treated with the same type of trabecular metal acetabular revision shell. The mean age at revision was 62.4 years (42 to 80) and the mean follow-up of both groups was 72.4 months (60 to 102). Clinical, radiological and functional outcomes were assessed. There were four (7.5%) mechanical failures in the <= 50% host bone contact group and no failures in the > 50% host bone contact group (p = 0.068). Out of both groups combined there were four infections (3.9%) and five recurrent dislocations (4.9%) with a stable acetabular component construct that were revised to a constrained liner. Given the complexity of the reconstructive challenge, porous metal revision acetabular shells show acceptable failure rates at five to ten years' follow-up in the setting of significant contained bone defects. This favourable outcome might be due to the improved initial stability achieved by a high coefficient of friction between the acetabular implant and the host bone, and the high porosity, which affords good bone ingrowth. PMID- 22323679 TI - The 15 degrees face-changing acetabular component for treatment of osteoarthritis secondary to developmental dysplasia of the hip. AB - We report the use of a 15 degrees face-changing cementless acetabular component in patients undergoing total hip replacement for osteoarthritis secondary to developmental dysplasia of the hip. The rationale behind its design and the surgical technique used for its implantation are described. It is distinctly different from a standard cementless hemispherical component as it is designed to position the bearing surface at the optimal angle of inclination, that is, < 45 degrees , while maximising the cover of the component by host bone. PMID- 22323680 TI - The use of femoral struts and impacted cancellous bone allograft in patients with severe femoral bone loss who undergo revision total hip replacement: a three- to nine-year follow-up. AB - We determined the midterm survival, incidence of peri-prosthetic fracture and the enhancement of the width of the femur when combining struts and impacted bone allografts in 24 patients (25 hips) with severe femoral bone loss who underwent revision hip surgery. The pre-operative diagnosis was aseptic loosening in 16 hips, second-stage reconstruction in seven, peri-prosthetic fracture in one and stem fracture in one hip. A total of 14 hips presented with an Endoklinik grade 4 defect and 11 hips a grade 3 defect. The mean pre-operative Merle D'Aubigne and Postel score was 5.5 points (1 to 8). The survivorship was 96% (95% confidence interval 72 to 98) at a mean of 54.5 months (36 to 109). The mean functional score was 17.3 points (16 to 18). One patient in which the strut did not completely bypass the femoral defect was further revised using a long cemented stem due to peri-prosthetic fracture at six months post-operatively. The mean subsidence of the stem was 1.6 mm (1 to 3). There was no evidence of osteolysis, resorption or radiolucencies during follow-up in any hip. Femoral width was enhanced by a mean of 41% (19% to 82%). A total of 24 hips had partial or complete bridging of the strut allografts. This combined biological method was associated with a favourable survivorship, a low incidence of peri-prosthetic fracture and enhancement of the width of the femur in revision total hip replacement in patients with severe proximal femoral bone loss. PMID- 22323681 TI - Early results of a novel technique using multiple small tantalum pegs for the treatment of osteonecrosis of the femoral head: a case series involving 26 hips. AB - The introduction of a trabecular tantalum rod has been proposed for the management of early-stage osteonecrosis of the femoral head but serves as a single-point of support of the necrotic lesion. We describe a technique using two or three 4.2 mm (or later 4.7 mm) tantalum pegs for the prevention of collapse of the necrotic lesion. We prospectively studied 21 patients (26 hips) with non traumatic osteonecrosis of the femoral head treated in this manner. Of these, 21 patients (24 hips) were available for radiological and clinical evaluation at a mean follow-up of 46 months (18 to 67). Radiological assessment showed that only eight hips deteriorated according to the Association Research Circulation Osseous classification, and four hips according to the Classification of the Japanese Investigation Committee of Health and Welfare. Functional improvement was obtained with an improvement in the mean Harris hip score from 65.2 (33.67 to 95) to 88.1 (51.72 to 100), the mean Merle D'Aubigne-Postel score from 13 (6 to 18) to 16 (11 to 18), a mean visual analogue score for pain from 5.2 (0 to 9.5) to 2.6 (0 to 7), and the mean Short-Form 36 score from 80.4 (56.8 to 107.1) to 92.4 (67.5 to 115.7). Of these 24 hips followed for a minimum of 18 months, three were considered as failures at the final follow-up, having required total hip replacement. One of the hips without full follow-up was also considered to be a failure. In more than two-thirds of the surviving hips a satisfactory clinical outcome was achieved with promising radiological findings. The estimated mean implant survival was 60 months (95% confidence interval 53.7 to 66.3). PMID- 22323682 TI - Use of multimodal intra-operative monitoring in averting nerve injury during complex hip surgery. AB - Peripheral nerve injury is an uncommon but serious complication of hip surgery that can adversely affect the outcome. Several studies have described the use of electromyography and intra-operative sensory evoked potentials for early warning of nerve injury. We assessed the results of multimodal intra-operative monitoring during complex hip surgery. We retrospectively analysed data collected between 2001 and 2010 from 69 patients who underwent complex hip surgery by a single surgeon using multimodal intra-operative monitoring from a total pool of 7894 patients who underwent hip surgery during this period. In 24 (35%) procedures the surgeon was alerted to a possible lesion to the sciatic and/or femoral nerve. Alerts were observed most frequently during peri-acetabular osteotomy. The surgeon adapted his approach based on interpretation of the neurophysiological changes. From 69 monitored surgical procedures, there was only one true positive case of post-operative nerve injury. There were no false positives or false negatives, and the remaining 68 cases were all true negative. The sensitivity for predicting post-operative nerve injury was 100% and the specificity 100%. We conclude that it is possible and appropriate to use this method during complex hip surgery and it is effective for alerting the surgeon to the possibility of nerve injury. PMID- 22323683 TI - Long-term results of arthroscopic excision of unstable osteochondral lesions of the lateral femoral condyle. AB - The purpose of this study was to evaluate the long-term functional and radiological outcomes of arthroscopic removal of unstable osteochondral lesions with subchondral drilling in the lateral femoral condyle. We reviewed the outcome of 23 patients (28 knees) with stage III or IV osteochondritis dissecans lesions of the lateral femoral condyle at a mean follow-up of 14 years (10 to 19). The functional clinical outcomes were assessed using the Lysholm score, which improved from a mean of 38.1 (SD 3.5) pre-operatively to a mean of 87.3 (SD 5.4) at the most recent review (p = 0.034), and the Tegner activity score, which improved from a pre-operative median of 2 (0 to 3) to a median of 5 (3 to 7) at final follow-up (p = 0.021). The radiological degenerative changes were evaluated according to Tapper and Hoover's classification and when compared with the pre operative findings, one knee had grade 1, 22 knees had grade 2 and five knees had grade 3 degenerative changes. The overall outcomes were assessed using Hughston's rating scale, where 19 knees were rated as good, four as fair and five as poor. We found radiological evidence of degenerative changes in the third or fourth decade of life at a mean of 14 years after arthroscopic excision of the loose body and subchondral drilling for an unstable osteochondral lesion of the lateral femoral condyle. Clinical and functional results were more satisfactory. PMID- 22323684 TI - Comparison of medial and lateral meniscal transplantation with regard to extrusion of the allograft, and its correlation with clinical outcome. AB - We compared extrusion of the allograft after medial and lateral meniscal allograft transplantation and examined the correlation between the extent of extrusion and the clinical outcome. A total of 73 lateral and 26 medial meniscus allografts were evaluated by MRI at a mean of 32 months (24 to 59) in 99 patients (67 men, 32 women) with a mean age of 35 years (21 to 52). The absolute values and the proportional widths of extruded menisci as a percentage were measured in coronal images that showed maximum extrusion. Functional assessments were performed using Lysholm scores. The mean extrusion was 4.7 mm (1.8 to 7.7) for lateral menisci and 2.9 mm (1.2 to 6.5) for medial menisci (p < 0.001), and the mean percentage extrusions were 52.0% (23.8% to 81.8%) and 31.2% (11.6% to 63.4%), respectively (p < 0.001). Mean Lysholm scores increased significantly from 49.0 (10 to 83) pre-operatively to 86.6 (33 to 99) at final follow-up for lateral menisci (p = 0.001) and from 50.9 (15 to 88) to 88.3 (32 to 100) for medial menisci (p < 0.001). The final mean Lysholm scores were similar in the two groups (p = 0.312). Furthermore, Lysholm scores were not found to be correlated with degree of extrusion (p = 0.242). Thus, transplanted lateral menisci extrude more significantly than transplanted medial menisci. However, the clinical outcome after meniscal transplantation was not found to be adversely affected by extrusion of the allograft. PMID- 22323685 TI - A prospective study comparing the functional outcome of computer-assisted and conventional total knee replacement. AB - The aim of this prospective single-centre study was to assess the difference in clinical outcome between total knee replacement (TKR) using computerised navigation and that of conventional TKR. We hypothesised that navigation would give a better result at every stage within the first five years. A total of 195 patients (195 knees) with a mean age of 70.0 years (39 to 89) were allocated alternately into two treatment groups, which used either conventional instrumentation (group A, 97 knees) or a navigation system (group B, 98 knees). After five years, complete clinical scores were available for 121 patients (62%). A total of 18 patients were lost to follow-up. Compared with conventional surgery, navigated TKR resulted in a better mean Knee Society score (p = 0.008). The difference in mean Knee Society scores over time between the two groups was not constant (p = 0.006), which suggests that these groups differed in their response to surgery with time. No significant difference in the frequency of malalignment was seen between the two groups. In summary, computerised navigation resulted in a better functional outcome at five years than conventional techniques. Given the similarity in mechanical alignment between the two groups, rotational alignment may prove to be a better method of identifying differences in clinical outcome after navigated surgery. PMID- 22323686 TI - Predictors of mortality after total knee replacement: a ten-year survivorship analysis. AB - We report the general mortality rate after total knee replacement and identify independent predictors of survival. We studied 2428 patients: there were 1127 men (46%) and 1301 (54%) women with a mean age of 69.3 years (28 to 94). Patients were allocated a predicted life expectancy based on their age and gender. There were 223 deaths during the study period. This represented an overall survivorship of 99% (95% confidence interval (CI) 98 to 99) at one year, 90% (95% CI 89 to 92) at five years, and 84% (95% CI 82 to 86) at ten years. There was no difference in survival by gender. A greater mortality rate was associated with increasing age (p < 0.001), American Society of Anesthesiologists (ASA) grade (p < 0.001), smoking (p < 0.001), body mass index (BMI) < 20 kg/m(2) (p < 0.001) and rheumatoid arthritis (p < 0.001). Multivariate modelling confirmed the independent effect of age, ASA grade, BMI, and rheumatoid disease on mortality. Based on the predicted average mortality, 114 patients were predicted to have died, whereas 217 actually died. This resulted in an overall excess standardised mortality ratio of 1.90. Patient mortality after TKR is predicted by their demographics: these could be used to assign an individual mortality risk after surgery. PMID- 22323687 TI - Acceleration of tendon-bone healing in anterior cruciate ligament reconstruction using an enamel matrix derivative in a rat model. AB - We examined whether enamel matrix derivative (EMD) could improve healing of the tendon-bone interface following reconstruction of the anterior cruciate ligament (ACL) using a hamstring tendon in a rat model. ACL reconstruction was performed in both knees of 30 Sprague-Dawley rats using the flexor digitorum tendon. The effect of commercially available EMD (EMDOGAIN), a preparation of matrix proteins from developing porcine teeth, was evaluated. In the left knee joint the space around the tendon-bone interface was filled with 40 ul of EMD mixed with propylene glycol alginate (PGA). In the right knee joint PGA alone was used. The ligament reconstructions were evaluated histologically and biomechanically at four, eight and 12 weeks (n = 5 at each time point). At eight weeks, EMD had induced a significant increase in collagen fibres connecting to bone at the tendon-bone interface (p = 0.047), whereas the control group had few fibres and the tendon-bone interface was composed of cellular and vascular fibrous tissues. At both eight and 12 weeks, the mean load to failure in the treated specimens was higher than in the controls (p = 0.009). EMD improved histological tendon-bone healing at eight weeks and biomechanical healing at both eight and 12 weeks. EMD might therefore have a human application to enhance tendon-bone repair in ACL reconstruction. PMID- 22323688 TI - Incidence of venous thromboembolism in elective foot and ankle surgery with and without aspirin prophylaxis. AB - The incidence of deep-vein thrombosis (DVT) and pulmonary embolism (PE) is thought to be low following foot and ankle surgery, but the routine use of chemoprophylaxis remains controversial. This retrospective study assessed the incidence of symptomatic venous thromboembolic (VTE) complications following a consecutive series of 2654 patients undergoing elective foot and ankle surgery. A total of 1078 patients received 75 mg aspirin as routine thromboprophylaxis between 2003 and 2006 and 1576 patients received no form of chemical thromboprophylaxis between 2007 and 2010. The overall incidence of VTE was 0.42% (DVT, 0.27%; PE, 0.15%) with 27 patients lost to follow-up. If these were included to create a worst case scenario, the overall VTE rate was 1.43%. There was no apparent protective effect against VTE by using aspirin. We conclude that the incidence of VTE following foot and ankle surgery is very low and routine use of chemoprophylaxis does not appear necessary for patients who are not in the high risk group for VTE. PMID- 22323689 TI - Responsiveness of the Manchester-Oxford Foot Questionnaire (MOXFQ) compared with AOFAS, SF-36 and EQ-5D assessments following foot or ankle surgery. AB - The responsiveness of the Manchester-Oxford Foot Questionnaire (MOXFQ) was compared with foot/ankle-specific and generic outcome measures used to assess all surgery of the foot and ankle. We recruited 671 consecutive adult patients awaiting foot or ankle surgery, of whom 427 (63.6%) were female, with a mean age of 52.8 years (18 to 89). They independently completed the MOXFQ, Short-Form 36 (SF-36) and EuroQol (EQ-5D) questionnaires pre-operatively and at a mean of nine months (3.8 to 14.4) post-operatively. Foot/ankle surgeons assessed American Orthopaedic Foot and Ankle Society (AOFAS) scores corresponding to four foot/ankle regions. A transition item measured perceived changes in foot/ankle problems post-surgery. Of 628 eligible patients proceeding to surgery, 491 (78%) completed questionnaires and 262 (42%) received clinical assessments both pre- and post-operatively. The regions receiving surgery were: multiple/whole foot in eight (1.3%), ankle/hindfoot in 292 (46.5%), mid-foot in 21 (3.3%), hallux in 196 (31.2%), and lesser toes in 111 (17.7%). Foot/ankle-specific MOXFQ, AOFAS and EQ 5D domains produced larger effect sizes (> 0.8) than any SF-36 domains, suggesting superior responsiveness. In analyses that anchored change in scores and effect sizes to patients' responses to a transition item about their foot/ankle problems, the MOXFQ performed well. The SF-36 and EQ-5D performed poorly. Similar analyses, conducted within foot-region based sub-groups of patients, found that the responsiveness of the MOXFQ was good compared with the AOFAS. This evidence supports the MOXFQ's suitability for assessing all foot and ankle surgery. PMID- 22323690 TI - Clinical and radiological results following radial osteotomy in patients with Kienbock's disease: four- to 18-year follow-up. AB - Radial osteotomy is currently advocated for patients with Lichtman's stages II and IIIA of Kienbock's disease; its place in the treatment of patients with stage IIIB disease remains controversial. The purpose of this study was to evaluate the medium-term results of this procedure and to compare the outcome in patients with stage IIIB disease and those with earlier stages (II and IIIA). A total of 18 patients (18 osteotomies) were evaluated both clinically and radiologically at a mean follow-up of 10.3 years (4 to 18). Range of movement, grip strength and pain improved significantly in all patients; the functional score (Nakamura Scoring System (NSSK)) was high and self-reported disability (Disabilities of Arm, Shoulder and Hand questionnaire) was low at the final follow-up in all patients evaluated. Patients with stage IIIB disease, however, had a significantly lower grip strength, lower NSSK scores and higher disability than those in less advanced stages. Radiological progression of the disease was not noted in either group, despite the stage. Radial osteotomy seems effective in halting the progression of disease and improving symptoms in stages II, IIIA and IIIB. Patients with less advanced disease should be expected to have better clinical results. PMID- 22323691 TI - The effects of an injury to the brain on bone healing and callus formation in young adults with fractures of the femoral shaft. AB - In patients with traumatic brain injury and fractures of long bones, it is often clinically observed that the rate of bone healing and extent of callus formation are increased. However, the evidence has been unconvincing and an association between such an injury and enhanced fracture healing remains unclear. We performed a retrospective cohort study of 74 young adult patients with a mean age of 24.2 years (16 to 40) who sustained a femoral shaft fracture (AO/OTA type 32A or 32B) with or without a brain injury. All the fractures were treated with closed intramedullary nailing. The main outcome measures included the time required for bridging callus formation (BCF) and the mean callus thickness (MCT) at the final follow-up. Comparative analyses were made between the 20 patients with a brain injury and the 54 without brain injury. Subgroup comparisons were performed among the patients with a brain injury in terms of the severity of head injury, the types of intracranial haemorrhage and gender. Patients with a brain injury had an earlier appearance of BCF (p < 0.001) and a greater final MCT value (p < 0.001) than those without. There were no significant differences with respect to the time required for BCF and final MCT values in terms of the severity of head injury (p = 0.521 and p = 0.153, respectively), the types of intracranial haemorrhage (p = 0.308 and p = 0.189, respectively) and gender (p = 0.383 and p = 0.662, respectively). These results confirm that an injury to the brain may be associated with accelerated fracture healing and enhanced callus formation. However, the severity of the injury to the brain, the type of intracranial haemorrhage and gender were not statistically significant factors in predicting the rate of bone healing and extent of final callus formation. PMID- 22323692 TI - Multiple fractures in the elderly. AB - We present the prevalence of multiple fractures in the elderly in a single catchment population of 780,000 treated over a 12-month period and describe the mechanisms of injury, common patterns of occurrence, management, and the associated mortality rate. A total of 2335 patients, aged >= 65 years of age, were prospectively assessed and of these 119 patients (5.1%) presented with multiple fractures. Distal radial (odds ratio (OR) 5.1, p < 0.0001), proximal humeral (OR 2.2, p < 0.0001) and pelvic (OR 4.9, p < 0.0001) fractures were associated with an increased risk of sustaining associated fractures. Only 4.5% of patients sustained multiple fractures after a simple fall, but due to the frequency of falls in the elderly this mechanism resulted in 80.7% of all multiple fractures. Most patients required admission (> 80%), of whom 42% did not need an operation but more than half needed an increased level of care before discharge (54%). The standardised mortality rate at one year was significantly greater after sustaining multiple fractures that included fractures of the pelvis, proximal humerus or proximal femur (p < 0.001). This mortality risk increased further if patients were < 80 years of age, indicating that the existence of multiple fractures after low-energy trauma is a marker of mortality. PMID- 22323693 TI - Factors affecting the incidence of deep wound infection after hip fracture surgery. AB - Prospective data on 6905 consecutive hip fracture patients at a district general hospital were analysed to identify the risk factors for the development of deep infection post-operatively. The main outcome measure was infection beneath the fascia lata. A total of 50 patients (0.7%) had deep infection. Operations by consultants or a specialist hip fracture surgeon had half the rate of deep infection compared with junior grades (p = 0.01). Increased duration of anaesthesia was significantly associated with deep infection (p = 0.01). The method of fracture fixation was also significant. Intracapsular fractures treated with a hemiarthroplasty had seven times the rate of deep infection compared with those treated by internal fixation (p = 0.001). Extracapsular fractures treated with an extramedullary device had a deep infection rate of 0.78% compared with 0% for those treated with intramedullary devices (p = 0.02). The management of hip fracture patients by a specialist hip fracture surgeon using appropriate fixation could significantly reduce the rate of deep infection and associated morbidity, along with extended hospitalisation and associated costs. PMID- 22323694 TI - Does plugging unused combination screw holes improve the fatigue life of fixation with locking plates in comminuted supracondylar fractures of the femur? AB - Filling the empty holes in peri-articular locking plates may improve the fatigue strength of the fixation. The purpose of this in vitro study was to investigate the effect of plugging the unused holes on the fatigue life of peri-articular distal femoral plates used to fix a comminuted supracondylar fracture model. A locking/compression plate was applied to 33 synthetic femurs and then a 6 cm metaphyseal defect was created (AO Type 33-A3). The specimens were then divided into three groups: unplugged, plugged with locking screw only and fully plugged holes. They were then tested using a stepwise or run-out fatigue protocol, each applying cyclic physiological multiaxial loads. All specimens in the stepwise group failed at the 770 N load level. The mean number of cycles to failure for the stepwise specimen was 25,500 cycles (SD 1500), 28,800 cycles (SD 6300), and 26,400 cycles (SD 2300) cycles for the unplugged, screw only and fully plugged configurations, respectively (p = 0.16). The mean number of cycles to failure for the run-out specimens was 42,800 cycles (SD 10,700), 36,000 cycles (SD 7200), and 36,600 cycles (SD 10,000) for the unplugged, screw only and fully plugged configurations, respectively (p = 0.50). There were also no differences in axial or torsional stiffness between the constructs. The failures were through the screw holes at the level of comminution. In conclusion, filling the empty combination locking/compression holes in peri-articular distal femur locking plates at the level of supracondylar comminution does not increase the fatigue life of the fixation in a comminuted supracondylar femoral fracture model (AO 33 A3) with a 6 cm gap. PMID- 22323695 TI - The relationship between microbiology results in the second of a two-stage exchange procedure using cement spacers and the outcome after revision total joint replacement for infection: the use of sonication to aid bacteriological analysis. AB - Patients with infected arthroplasties are normally treated with a two-stage exchange procedure using polymethylmethacrylate bone cement spacers impregnated with antibiotics. However, spacers may act as a foreign body to which micro organisms may adhere and grow. In this study it was hypothesised that subclinical infection may be diagnosed with sonication of the surface biofilm of the spacer. The aims were to assess the presence of subclinical infection through sonication of the spacer at the time of a second-stage procedure, and to determine the relationship between subclinical infection and the clinical outcome. Of 55 patients studied, 11 (20%) were diagnosed with subclinical infection. At a mean follow-up of 12 months (interquartile range 6 to 18), clinical failure was found in 18 (32.7%) patients. Of the patients previously diagnosed with subclinical infection, 63% (7 of 11) had failed compared with 25% (11 of 44) of those without subclinical infection (odds ratio 5.25, 95% confidence interval 1.29 to 21.4, p = 0.021). Sonication of the biofilm of the surface of the spacer is useful in order to exclude subclinical infection and therefore contributes to improving the outcome after two-stage procedures. PMID- 22323696 TI - Do forced air patient-warming devices disrupt unidirectional downward airflow? AB - Patient warming significantly decreases the risk of surgical site infection. Recently there have been concerns that forced air warming may interfere with unidirectional airflow, potentially posing an increased risk of infection. Our null hypothesis was that forced air and radiant warming devices do not increase the temperature and the number of particles over the surgical site when compared with no warming device. A forced air warming device was compared with a radiant warming device and no warming device as a control. The temperature and number of particles were measured over the surgical site. The theatre was prepared as for a routine lower-limb arthroplasty operation, and the same volunteer was used throughout the study. Forced air warming resulted in a significant mean increase in the temperature (1.1 degrees C vs 0.4 degrees C, p < 0.0001) and number of particles (1038.2 vs 274.8, p = 0.0087) over the surgical site when compared with radiant warming, which raises concern as bacteria are known to require particles for transport. PMID- 22323697 TI - Apixaban versus enoxaparin for thromboprophylaxis after hip or knee replacement: pooled analysis of major venous thromboembolism and bleeding in 8464 patients from the ADVANCE-2 and ADVANCE-3 trials. AB - In order to compare the effect of oral apixaban (a factor Xa inhibitor) with subcutaneous enoxaparin on major venous thromboembolism and major and non-major clinically relevant bleeding after total knee and hip replacement, we conducted a pooled analysis of two previously reported double-blind randomised studies involving 8464 patients. One group received apixaban 2.5 mg twice daily (plus placebo injection) starting 12 to 24 hours after operation, and the other received enoxaparin subcutaneously once daily (and placebo tablets) starting 12 hours (+/- 3) pre-operatively. Each regimen was continued for 12 days (+/- 2) after knee and 35 days (+/- 3) after hip arthroplasty. All outcomes were centrally adjudicated. Major venous thromboembolism occurred in 23 of 3394 (0.7%) evaluable apixaban patients and in 51 of 3394 (1.5%) evaluable enoxaparin patients (risk difference, apixaban minus enoxaparin, -0.8% (95% confidence interval (CI) -1.2 to -0.3); two-sided p = 0.001 for superiority). Major bleeding occurred in 31 of 4174 (0.7%) apixaban patients and 32 of 4167 (0.8%) enoxaparin patients (risk difference -0.02% (95% CI -0.4 to 0.4)). Combined major and clinically relevant non-major bleeding occurred in 182 (4.4%) apixaban patients and 206 (4.9%) enoxaparin patients (risk difference -0.6% (95% CI -1.5 to 0.3)). Apixaban 2.5 mg twice daily is more effective than enoxaparin 40 mg once daily without increased bleeding. PMID- 22323698 TI - Early results of a non-invasive extendible prosthesis for limb-salvage surgery in children with bone tumours. AB - We reviewed our initial seven-year experience with a non-invasive extendible prosthesis in 34 children with primary bone tumours. The distal femur was replaced in 25 cases, total femur in five, proximal femur in one and proximal tibia in three. The mean follow-up was 44 months (15 to 86) and 27 patients (79%) remain alive. The prostheses were lengthened by an electromagnetic induction mechanism in an outpatient setting and a mean extension of 32 mm (4 to 80) was achieved without anaesthesia. There were lengthening complications in two children: failed lengthening in one and the formation of scar tissue in the other. Deep infection developed in six patients (18%) and local recurrence in three. A total of 11 patients required further surgery to the leg. Amputation was necessary in five patients (20%) and a two-stage revision in another. There were no cases of loosening, but two patients had implant breakage and required revision. The mean Musculoskeletal Tumor Society functional score was 85% (60% to 100%) at last known follow-up. These early results demonstrate that the non invasive extendible prosthesis allows successful lengthening without surgical intervention, but the high incidence of infection is a cause for concern. PMID- 22323699 TI - Efficacy and late complications of percutaneous epiphysiodesis with transphyseal screws. AB - Percutaneous epiphysiodesis using transphyseal screws (PETS) has been developed for the treatment of lower limb discrepancies with the aim of replacing traditional open procedures. The goal of this study was to evaluate its efficacy and safety at skeletal maturity. A total of 45 consecutive patients with a mean skeletal age of 12.7 years (8.5 to 15) were included and followed until maturity. The mean efficacy of the femoral epiphysiodesis was 35% (14% to 87%) at six months and 66% (21% to 100%) at maturity. The mean efficacy of the tibial epiphysiodesis was 46% (18% to 73%) at six months and 66% (25% to 100%) at maturity. In both groups of patients the under-correction was significantly reduced between six months post-operatively and skeletal maturity. The overall rate of revision was 18% (eight patients), and seven of these revisions (87.5%) involved the tibia. This series showed that use of the PETS technique in the femur was safe, but that its use in the tibia was associated with a significant rate of complications, including a valgus deformity in nine patients (20%), leading us to abandon it in the tibia. The arrest of growth was delayed and the final loss of growth at maturity was only 66% of that predicted pre-operatively. This should be taken into account in the pre-operative planning. PMID- 22323700 TI - Predictors of the accuracy of quotation of references in peer-reviewed orthopaedic literature in relation to publications on the scaphoid. AB - Using inaccurate quotations can propagate misleading information, which might affect the management of patients. The aim of this study was to determine the predictors of quotation inaccuracy in the peer-reviewed orthopaedic literature related to the scaphoid. We randomly selected 100 papers from ten orthopaedic journals. All references were retrieved in full text when available or otherwise excluded. Two observers independently rated all quotations from the selected papers by comparing the claims made by the authors with the data and expressed opinions of the reference source. A statistical analysis determined which article related factors were predictors of quotation inaccuracy. The mean total inaccuracy rate of the 3840 verified quotes was 7.6%. There was no correlation between the rate of inaccuracy and the impact factor of the journal. Multivariable analysis identified the journal and the type of study (clinical, biomechanical, methodological, case report or review) as important predictors of the total quotation inaccuracy rate. We concluded that inaccurate quotations in the peer-reviewed orthopaedic literature related to the scaphoid were common and slightly more so for certain journals and certain study types. Authors, reviewers and editorial staff play an important role in reducing this inaccuracy. PMID- 22323701 TI - Mixing and matching causing taper wear: corrosion associated with pseudotumour formation. AB - We report a case of a male patient presenting with bilateral painful but apparently well-positioned and -fixed large-diameter metal-on-metal hip replacements four years post-operatively. Multiple imaging modes revealed a thick walled, cystic expansile mass in communication with the hip joint (a pseudotumour). Implant retrieval analysis and tissue culture eliminated high bearing wear or infection as causes for the soft-tissue reaction, but noted marked corrosion of the modular neck taper adaptor and corrosion products in the tissues. Therefore, we believe corrosion products from the taper caused by mismatch of the implant components led to pseudotumour formation requiring revision. PMID- 22323703 TI - Learning from default mode network: the predictive value of resting state in traumatic brain injury. PMID- 22323704 TI - A dynamic cortical network encodes violations of expectancy during taste perception. PMID- 22323705 TI - Serotonin activates overall feeding by activating two separate neural pathways in Caenorhabditis elegans. AB - Food intake in the nematode Caenorhabditis elegans requires two distinct feeding motions, pharyngeal pumping and isthmus peristalsis. Bacteria, the natural food of C. elegans, activate both feeding motions (Croll, 1978; Horvitz et al., 1982; Chiang et al., 2006). The mechanisms by which bacteria activate the feeding motions are largely unknown. To understand the process, we studied how serotonin, an endogenous pharyngeal pumping activator whose action is triggered by bacteria, activates feeding motions. Here, we show that serotonin, like bacteria, activates overall feeding by activating isthmus peristalsis as well as pharyngeal pumping. During active feeding, the frequencies and the timing of onset of the two motions were distinct, but each isthmus peristalsis was coupled to the preceding pump. We found that serotonin activates the two feeding motions mainly by activating two separate neural pathways in response to bacteria. For activating pumping, the SER 7 serotonin receptor in the MC motor neurons in the feeding organ activated cholinergic transmission from MC to the pharyngeal muscles by activating the Gsalpha signaling pathway. For activating isthmus peristalsis, SER-7 in the M4 (and possibly M2) motor neuron in the feeding organ activated the G(12)alpha signaling pathway in a cell-autonomous manner, which presumably activates neurotransmission from M4 to the pharyngeal muscles. Based on our results and previous calcium imaging of pharyngeal muscles (Shimozono et al., 2004), we propose a model that explains how the two feeding motions are separately regulated yet coupled. The feeding organ may have evolved this way to support efficient feeding. PMID- 22323707 TI - Temporal order memory assessed during spatiotemporal navigation as a behavioral cognitive marker for differential Alzheimer's disease diagnosis. AB - Episodic memory impairment is a hallmark for early diagnosis of Alzheimer's disease. Most actual tests used to diagnose Alzheimer's disease do not assess the spatiotemporal properties of episodic memory and lead to false-positive or negative diagnosis. We used a newly developed, nonverbal navigation test for Human, based on the objective experimental testing of a spatiotemporal experience, to differentially Alzheimer's disease at the mild stage (N = 16 patients) from frontotemporal lobar degeneration (N = 11 patients) and normal aging (N = 24 subjects). Comparing navigation parameters and standard neuropsychological tests, temporal order memory appeared to have the highest predictive power for mild Alzheimer's disease diagnosis versus frontotemporal lobar degeneration and normal aging. This test was also nonredundant with classical neuropsychological tests. As a conclusion, our results suggest that temporal order memory tested in a spatial navigation task may provide a selective behavioral marker of Alzheimer's disease. PMID- 22323706 TI - Redundant catecholamine signaling consolidates fear memory via phospholipase C. AB - Memories for emotionally arousing experiences are typically vivid and persistent. The recurrent, intrusive memories of traumatic events in post-traumatic stress disorder (PTSD) are an extreme example. Stress-responsive neurotransmitters released during emotional arousal are proposed to enhance the consolidation of fear memory. These transmitters may include norepinephrine and epinephrine (NE/E) because stimulating beta-adrenergic receptors shortly after training can enhance memory consolidation. However, mice lacking NE/E acquire and consolidate fear memory normally. Here, we show by using pharmacologic and genetic manipulations in mice and rats that NE/E are not essential for classical fear memory consolidation because signaling by the beta(2)-adrenergic receptor is redundant with signaling by dopamine at the D(5)-dopaminergic receptor. The intracellular signaling that is stimulated by these receptors to promote consolidation uses distinct G proteins to redundantly activate phospholipase C. The results support recent evidence indicating that blocking beta-adrenergic receptors alone shortly after trauma may not be sufficient to prevent PTSD. PMID- 22323708 TI - alpha/beta oscillations indicate inhibition of interfering visual memories. AB - Selective retrieval of a specific target memory often leads to the forgetting of related but irrelevant memories. Current cognitive theory states that such retrieval-induced forgetting arises due to inhibition of competing memory traces. To date, however, direct neural evidence for this claim has not been forthcoming. Studies on selective attention suggest that cortical inhibition is mediated by increased brain oscillatory activity in the alpha/beta frequency band. The present study, testing 18 human subjects, investigated whether these mechanisms can be generalized to selective memory retrieval in which competing memories interfere with the retrieval of a target memory. Our experiment was designed so that each cue used to search memory was associated with a target memory and a competitor memory stored in separate brain hemispheres. Retrieval-induced forgetting was observed in a condition in which the competitor memory interfered with target retrieval. Increased oscillatory alpha/beta power was observed over the hemisphere housing the sensory representation of the competitor memory trace and predicted the amount of retrieval-induced forgetting in the subsequent memory test. These results provide the first direct evidence for inhibition of competing memories during episodic memory retrieval and suggest that competitive retrieval is governed by inhibitory mechanisms similar to those employed in selective attention. PMID- 22323709 TI - Absence of TI-VAMP/Vamp7 leads to increased anxiety in mice. AB - Vesicular (v)- and target (t)-SNARE proteins assemble in SNARE complex to mediate membrane fusion. Tetanus neurotoxin-insensitive vesicular-associated membrane protein (TI-VAMP/VAMP7), a vesicular SNARE expressed in several cell types including neurons, was previously shown to play a major role in exocytosis involved in neurite growth in cultured neurons. Here we generated a complete constitutive knock-out by deleting the exon 3 of Vamp7. Loss of TI-VAMP expression did not lead to any striking developmental or neurological defect. Knock-out mice displayed decreased brain weight and increased third ventricle volume. Axon growth appeared normal in cultured knock-out neurons. Behavioral characterization unraveled that TI-VAMP knock-out was associated with increased anxiety. Our results thus suggest compensatory mechanisms allowing the TI-VAMP knock-out mice to fulfill major developmental processes. The phenotypic traits unraveled here further indicate an unexpected role of TI-VAMP-mediated vesicular traffic in anxiety and suggest a role for TI-VAMP in higher brain functions. PMID- 22323710 TI - When up is down in 0g: how gravity sensing affects the timing of interceptive actions. AB - Humans are known to regulate the timing of interceptive actions by modeling, in a simplified way, Newtonian mechanics. Specifically, when intercepting an approaching ball, humans trigger their movements a bit earlier when the target arrives from above than from below. This bias occurs regardless of the ball's true kinetics, and thus appears to reflect an a priori expectation that a downward moving object will accelerate. We postulate that gravito-inertial information is used to tune visuomotor responses to match the target's most likely acceleration. Here we used the peculiar conditions of parabolic flight- where gravity's effects change every 20 s--to test this hypothesis. We found a striking reversal in the timing of interceptive responses performed in weightlessness compared with trials performed on ground, indicating a role of gravity sensing in the tuning of this response. Parallels between these observations and the properties of otolith receptors suggest that vestibular signals themselves might plausibly provide the critical input. Thus, in addition to its acknowledged importance for postural control, gaze stabilization, and spatial navigation, we propose that detecting the direction of gravity's pull plays a role in coordinating quick reactions intended to intercept a fast-moving visual target. PMID- 22323711 TI - Coding of microsaccades in three-dimensional space by premotor saccadic neurons. AB - Microsaccades are small, involuntary eye movements that are produced during fixation. While accurate visual perception requires precise binocular coordination during fixation, previous studies of the neural control of microsaccades measured the movement of one eye only. Here we show how premotor saccadic neurons control these small fixational eye movements in three dimensional space. Microsaccadic eye movements, produced by monkeys trained to fixate targets presented at different depths, were similarly distributed in three dimensional space during both near and far viewing. Single unit recordings of the neural activity of premotor neurons further revealed that the brainstem saccadic circuitry controls these minute disconjugate shifts of gaze by preferentially encoding the dynamic movement of an individual eye (i.e., integrated control of conjugate and vergence motion). These findings challenge the traditional notion that microsaccades are strictly conjugate and have important implications for studies that use microsaccades to evaluate visual and attentional processing, as well as certain neurological disorders. PMID- 22323712 TI - Posttraining transcranial magnetic stimulation of striate cortex disrupts consolidation early in visual skill learning. AB - Practice-induced improvements in skilled performance reflect "offline " consolidation processes extending beyond daily training sessions. According to visual learning theories, an early, fast learning phase driven by high-level areas is followed by a late, asymptotic learning phase driven by low-level, retinotopic areas when higher resolution is required. Thus, low-level areas would not contribute to learning and offline consolidation until late learning. Recent studies have challenged this notion, demonstrating modified responses to trained stimuli in primary visual cortex (V1) and offline activity after very limited training. However, the behavioral relevance of modified V1 activity for offline consolidation of visual skill memory in V1 after early training sessions remains unclear. Here, we used neuronavigated transcranial magnetic stimulation (TMS) directed to a trained retinotopic V1 location to test for behaviorally relevant consolidation in human low-level visual cortex. Applying TMS to the trained V1 location within 45 min of the first or second training session strongly interfered with learning, as measured by impaired performance the next day. The interference was conditional on task context and occurred only when training in the location targeted by TMS was followed by training in a second location before TMS. In this condition, high-level areas may become coupled to the second location and uncoupled from the previously trained low-level representation, thereby rendering consolidation vulnerable to interference. Our data show that, during the earliest phases of skill learning in the lowest-level visual areas, a behaviorally relevant form of consolidation exists of which the robustness is controlled by high-level, contextual factors. PMID- 22323713 TI - Cracking down on inhibition: selective removal of GABAergic interneurons from hippocampal networks. AB - Inhibitory (GABAergic) interneurons entrain assemblies of excitatory principal neurons to orchestrate information processing in the hippocampus. Disrupting the dynamic recruitment as well as the temporally precise activity of interneurons in hippocampal circuitries can manifest in epileptiform seizures, and impact specific behavioral traits. Despite the importance of GABAergic interneurons during information encoding in the brain, experimental tools to selectively manipulate GABAergic neurotransmission are limited. Here, we report the selective elimination of GABAergic interneurons by a ribosome inactivation approach through delivery of saporin-conjugated anti-vesicular GABA transporter antibodies (SAVAs) in vitro as well as in the mouse and rat hippocampus in vivo. We demonstrate the selective loss of GABAergic--but not glutamatergic--synapses, reduced GABA release, and a shift in excitation/inhibition balance in mixed cultures of hippocampal neurons exposed to SAVAs. We also show the focal and indiscriminate loss of calbindin(+), calretinin(+), parvalbumin/system A transporter 1(+), somatostatin(+), vesicular glutamate transporter 3 (VGLUT3)/cholecystokinin/CB(1) cannabinoid receptor(+) and neuropeptide Y(+) local-circuit interneurons upon SAVA microlesions to the CA1 subfield of the rodent hippocampus, with interneuron debris phagocytosed by infiltrating microglia. SAVA microlesions did not affect VGLUT1(+) excitatory afferents. Yet SAVA-induced rearrangement of the hippocampal circuitry triggered network hyperexcitability associated with the progressive loss of CA1 pyramidal cells and the dispersion of dentate granule cells. Overall, our data identify SAVAs as an effective tool to eliminate GABAergic neurons from neuronal circuits underpinning high-order behaviors and cognition, and whose manipulation can recapitulate pathogenic cascades of epilepsy and other neuropsychiatric illnesses. PMID- 22323714 TI - Impact of the NGF maturation and degradation pathway on the cortical cholinergic system phenotype. AB - Cortical cholinergic atrophy plays a significant role in the cognitive loss seen with aging and in Alzheimer's disease (AD), but the mechanisms leading to it remain unresolved. Nerve growth factor (NGF) is the neurotrophin responsible for the phenotypic maintenance of basal forebrain cholinergic neurons in the mature and fully differentiated CNS. In consequence, its implication in cholinergic atrophy has been suspected; however, no mechanistic explanation has been provided. We have previously shown that the precursor of NGF (proNGF) is cleaved extracellularly by plasmin to form mature NGF (mNGF) and that mNGF is degraded by matrix metalloproteinase 9. Using cognitive-behavioral tests, Western blotting, and confocal and electron microscopy, this study demonstrates that a pharmacologically induced chronic failure in extracellular NGF maturation leads to a reduction in mNGF levels, proNGF accumulation, cholinergic degeneration, and cognitive impairment in rats. It also shows that inhibiting NGF degradation increases endogenous levels of the mature neurotrophin and increases the density of cortical cholinergic boutons. Together, the data point to a mechanism explaining cholinergic loss in neurodegenerative conditions such as AD and provide a potential therapeutic target for the protection or restoration of this CNS transmitter system in aging and AD. PMID- 22323715 TI - No dissociation between perception and action in patient DF when haptic feedback is withdrawn. AB - Goodale et al. (1991) reported a striking dissociation between vision for perception and action. They examined DF, a human patient who had damage to her ventral visual stream and suffered from visual form agnosia. She was unable to perceive an object's size but could match the opening of her hand to the object's size during grasping. It was concluded that grasping relied on a separate representation of visual size in the dorsal stream and required no visual input from the ventral stream. This observation inspired the influential perception action model, which claimed separate visual streams for perception and action. However, in grasping (but not in corresponding perceptual tasks), participants receive haptic feedback after each trial. Using this feedback, DF might compensate for her impaired size-vision. I reexamined DF's grasping behavior using a mirror apparatus to dissociate the image of an object from its physical presence. DF's grasping was only normal when she received haptic feedback. Thus, in grasping, DF can rely on haptic feedback to compensate for her deficit in size perception. This can explain why her grasping is significantly better than her perceptual performance. The findings emphasize the extent of early interstream interactions and highlight the multimodal nature of sensory processing in the dorsal stream. PMID- 22323716 TI - Generation of a pain memory in the primary afferent nociceptor triggered by PKCepsilon activation of CPEB. AB - Isolectin B(4)-positive [IB(4)(+)] primary afferent nociceptors challenged with an inflammatory or neuropathic insult develop a PKCepsilon-dependent long-lasting hyperalgesic response to a subsequent challenge by the proinflammatory cytokine prostaglandin E(2) (PGE(2)), a phenomenon known as hyperalgesic priming. Here we demonstrate that the neuroplasticity underlying nociceptor priming requires 72 h to be established; rats that have been challenged with the inflammatory mediator TNFalpha 24 or 48 h ahead of PGE(2) do not show the enhanced and prolonged hyperalgesic response by which primed IB(4)(+)-nociceptors are being characterized. Moreover, as the underlying plasticity can be interrupted by the peripheral administration of the protein translation inhibitor anisomycin it is reflected by changes in the peripheral protein expression pattern. Finally, the induction of priming by the selective PKCepsilon agonist, psi epsilon receptor for activated c kinase (psiepsilonRACK) can be prevented, but not reversed by intrathecal injections of antisense oligodeoxynucleotides for the cytoplasmic polyadenylation element binding protein (CPEB) mRNA, a master regulator of protein translation that coimmunoprecipitated with PKCepsilon and is almost exclusively expressed by IB(4)(+)-nociceptors. Our results suggest that CPEB is downstream of PKCepsilon in the cellular signaling cascade responsible for the induction of priming, raising the intriguing possiblity that prion-like misfolding could be a responsible mechanism for the chronification of pain. PMID- 22323717 TI - Ventral striatum encodes past and predicted value independent of motor contingencies. AB - The ventral striatum (VS) is thought to signal the predicted value of expected outcomes. However, it is still unclear whether VS can encode value independently from variables often yoked to value such as response direction and latency. Expectations of high value reward are often associated with a particular action and faster latencies. To address this issue we trained rats to perform a task in which the size of the predicted reward was signaled before the instrumental response was instructed. Instrumental directional cues were presented briefly at a variable onset to reduce accuracy and increase reaction time. Rats were more accurate and slower when a large versus small reward was at stake. We found that activity in VS was high during odors that predicted large reward even though reaction times were slower under these conditions. In addition to these effects, we found that activity before the reward predicting cue reflected past and predicted reward. These results demonstrate that VS can encode value independent of motor contingencies and that the role of VS in goal-directed behavior is not just to increase vigor of specific actions when more is at stake. PMID- 22323718 TI - Differential effects between gamma-secretase inhibitors and modulators on cognitive function in amyloid precursor protein-transgenic and nontransgenic mice. AB - gamma-Secretase inhibitors (GSIs) reduce amyloid-beta (Abeta) peptides but inevitably increase the beta-C-terminal fragment (beta-CTF) of amyloid precursor protein (APP), potentially having undesirable effects on synapses. In contrast, gamma-secretase modulators (GSMs) reduce Abeta42 without increasing beta-CTF. Although the Abeta-lowering effects of these compounds have been extensively studied, little effort has been made to investigate their effects on cognition. Here, we compared the effects of two GSIs--(2S)-2-hydroxy-3-methyl-N-[(2S)-1 {[(1S)-3-methyl-2-oxo-2,3,4,5-tetrahydro-1H-3-benzazepin-1-yl]amino}-1-oxopropan 2-yl]butanamide (LY450139, semagacestat) and (2R)-2-[[(4 chlorophenyl)sulfonyl][[2-fluoro-4-(1,2,4-oxazol-3-yl)phenyl]methyl]amino-5,5,5 trifluoropentanamide (BMS-708163)--and a second-generation GSM [{(2S,4R)-1-[(4R) 1,1,1-trifluoro-7-methyloctan-4-yl]-2-[4-(trifluoromethyl)phenyl]piperidin-4 yl}acetic acid (GSM-2)] on spatial working memory in APP-transgenic (Tg2576) and nontransgenic mice using the Y-maze task. While acute dosing with either GSI ameliorated memory deficits in 5.5-month-old Tg2576 mice, these effects disappeared after 8 d subchronic dosing. Subchronic dosing with either GSI rather impaired normal cognition in 3-month-old Tg2576 mice, with no inhibition on the processing of other gamma-secretase substrates, such as Notch, N-cadherin, or EphA4, in the brain. LY450139 also impaired normal cognition in wild-type mice; however, the potency was 10-fold lower than that in Tg2576 mice, indicating an APP-dependent mechanism likely with beta-CTF accumulation. Immunofluorescence studies revealed that the beta-CTF accumulation was localized in the presynaptic terminals of the hippocampal stratum lucidum and dentate hilus, implying an effect on presynaptic function in the mossy fibers. In contrast, both acute and subchronic dosing with GSM-2 significantly ameliorated memory deficits in Tg2576 mice and did not affect normal cognition in wild-type mice. We demonstrated a clear difference between GSI and GSM in effects on functional consequences, providing new insights into strategies for developing these drugs against Alzheimer's disease. PMID- 22323719 TI - Angiotensin type 1A receptors in C1 neurons of the rostral ventrolateral medulla modulate the pressor response to aversive stress. AB - The rise in blood pressure during an acute aversive stress has been suggested to involve activation of angiotensin type 1A receptors (AT(1A)Rs) at various sites within the brain, including the rostral ventrolateral medulla. In this study we examine the involvement of AT(1A)Rs associated with a subclass of sympathetic premotor neurons of the rostral ventrolateral medulla, the C1 neurons. The distribution of putative AT(1A)R-expressing cells was mapped throughout the brains of three transgenic mice with a bacterial artificial chromosome-expressing green fluorescent protein under the control of the AT(1A)R promoter. The overall distribution correlated with that of the AT(1A)Rs mapped by other methods and demonstrated that the majority of C1 neurons express the AT(1A)R. Cre-recombinase expression in C1 neurons of AT(1A)R-floxed mice enabled demonstration that the pressor response to microinjection of angiotensin II into the rostral ventrolateral medulla is dependent upon expression of the AT(1A)R in these neurons. Lentiviral-induced expression of wild-type AT(1A)Rs in C1 neurons of global AT(1A)R knock-out mice, implanted with radiotelemeter devices for recording blood pressure, modulated the pressor response to aversive stress. During prolonged cage-switch stress, expression of AT(1A)Rs in C1 neurons induced a greater sustained pressor response when compared to the control viral-injected group (22 +/- 4 mmHg for AT(1A)R vs 10 +/- 1 mmHg for GFP; p < 0.001), which was restored toward that of the wild-type group (28 +/- 2 mmHg). This study demonstrates that AT(1A)R expression by C1 neurons is essential for the pressor response to angiotensin II and that this pathway plays an important role in the pressor response to aversive stress. PMID- 22323720 TI - Plasticity of subventricular zone neuroprogenitors in MPTP (1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine) mouse model of Parkinson's disease involves cross talk between inflammatory and Wnt/beta-catenin signaling pathways: functional consequences for neuroprotection and repair. AB - In Parkinson's disease (PD), neurogenesis is impaired in the subventricular zone (SVZ) of postmortem human PD brains, in primate nonhuman and rodent models of PD. The vital role of Wingless-type MMTV integration site (Wnt)/beta-catenin signaling in the modulation of neurogenesis, neuroprotection, and synaptic plasticity coupled to our recent findings uncovering an active role for inflammation and Wnt/beta-catenin signaling in MPTP-induced loss and repair of nigrostriatal dopaminergic (DAergic) neurons prompted us to study the impact of neuroinflammation and the Wnt/beta-catenin pathway in the response of SVZ neuroprogenitors (NPCs) in MPTP-treated mice. In vivo experiments, using bromodeoxyuridine and cell-specific markers, and ex vivo time course analyses documented an inverse correlation between the reduced proliferation of NPCs and the generation of new neuroblasts with the phase of maximal exacerbation of microglia reaction, whereas a shift in the microglia proinflammatory phenotype correlated with a progressive NPC recovery. Ex vivo and in vitro experiments using microglia-NPC coculture paradigms pointed to NADPH-oxidase (gpPHOX(91)), a major source of microglial ROS, and reactive nitrogen species as candidate inhibitors of NPC neurogenic potential via the activation of glycogen synthase 3 (pGSK-3beta(Tyr216)), leading to loss of beta-catenin, a chief downstream transcriptional effector. Accordingly, MPTP/MPP(+) (1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine) caused beta-catenin downregulation and pGSK-3beta(Tyr216) overexpression, whereas manipulation of Wnt/beta-catenin signaling with RNA interference-mediated GSK-3beta knockdown or GSK-3beta antagonism reversed MPTP induced neurogenic impairment ex vivo/in vitro or in vivo. Reciprocally, pharmacological modulation of inflammation prevented beta-catenin downregulation and restored neurogenesis, suggesting the possibility to modulate this endogenous system with potential consequences for DAergic neuroprotection and self-repair. PMID- 22323721 TI - Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature. AB - We studied N-(2-aminoethyl)-N-(4-(benzyloxy)-3-methoxybenzyl)thiophene-2 carboxamide hydrochloride (M8-B), a selective and potent antagonist of the transient receptor potential melastatin-8 (TRPM8) channel. In vitro, M8-B blocked cold-induced and TRPM8-agonist-induced activation of rat, human, and murine TRPM8 channels, including those on primary sensory neurons. In vivo, M8-B decreased deep body temperature (T(b)) in Trpm8(+/+) mice and rats, but not in Trpm8(-/-) mice, thus suggesting an on-target action. Intravenous administration of M8-B was more effective in decreasing T(b) in rats than intrathecal or intracerebroventricular administration, indicating a peripheral action. M8-B attenuated cold-induced c-Fos expression in the lateral parabrachial nucleus, thus indicating a site of action within the cutaneous cooling neural pathway to thermoeffectors, presumably on sensory neurons. A low intravenous dose of M8-B did not affect T(b) at either a constantly high or a constantly low ambient temperature (T(a)), but the same dose readily decreased T(b) if rats were kept at a high T(a) during the M8-B infusion and transferred to a low T(a) immediately thereafter. These data suggest that both a successful delivery of M8-B to the skin (high cutaneous perfusion) and the activation of cutaneous TRPM8 channels (by cold) are required for the hypothermic action of M8-B. At tail-skin temperatures <23 degrees C, the magnitude of the M8-B-induced decrease in T(b) was inversely related to skin temperature, thus suggesting that M8-B blocks thermal (cold) activation of TRPM8. M8-B affected all thermoeffectors studied (thermopreferendum, tail-skin vasoconstriction, and brown fat thermogenesis), thus suggesting that TRPM8 is a universal cold receptor in the thermoregulation system. PMID- 22323722 TI - Exogenous leukemia inhibitory factor stimulates oligodendrocyte progenitor cell proliferation and enhances hippocampal remyelination. AB - New CNS neurons and glia are generated throughout adulthood from endogenous neural stem and progenitor cells. These progenitors can respond to injury, but their ability to proliferate, migrate, differentiate, and survive is usually insufficient to replace lost cells and restore normal function. Potentiating the progenitor response with exogenous factors is an attractive strategy for the treatment of nervous system injuries and neurodegenerative and demyelinating disorders. Previously, we reported that delivery of leukemia inhibitory factor (LIF) to the CNS stimulates the self-renewal of neural stem cells and the proliferation of parenchymal glial progenitors. Here we identify these parenchymal glia as oligodendrocyte (OL) progenitor cells (OPCs) and show that LIF delivery stimulates their proliferation through the activation of gp130 receptor signaling within these cells. Importantly, this effect of LIF on OPC proliferation can be harnessed to enhance the generation of OLs that express myelin proteins and reform nodes of Ranvier in the context of chronic demyelination in the adult mouse hippocampus. Our findings, considered together with the known beneficial effects of LIF on OL and neuron survival, suggest that LIF has both reparative and protective activities that make it a promising potential therapy for CNS demyelinating disorders and injuries. PMID- 22323723 TI - A Phox2- and Hand2-dependent Hand1 cis-regulatory element reveals a unique gene dosage requirement for Hand2 during sympathetic neurogenesis. AB - Neural crest cell specification and differentiation to a sympathetic neuronal fate serves as an important model for neurogenesis and depends upon the function of both bHLH transcription factors, notably Hand2, and homeodomain transcription factors, including Phox2b. Here, we define a 1007 bp cis-regulatory element 5' of the Hand1 gene sufficient to drive reporter expression within the sympathetic chain of transgenic mice. Comparative genomic analyses uncovered evolutionarily conserved consensus-binding sites within this element, which chromatin immunoprecipitation and electrophoretic mobility shift assays confirm are bound by Hand2 and Phox2b. Mutational analyses revealed that the conserved Phox2 and E box binding sites are necessary for proper cis-regulatory element activity, and expression analyses on both Hand2 conditionally null and hypomorphic backgrounds demonstrate that Hand2 is required for reporter activation in a gene dosage dependent manner. We demonstrate that Hand2 and Hand1 differentially bind the E boxes in this cis-regulatory element, establishing molecular differences between these two factors. Finally, we demonstrate that Hand1 is dispensable for normal tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) expression in sympathetic neurons, even when Hand2 gene dosage is concurrently reduced by half. Together, these data define a tissue-specific Hand1 cis-regulatory element controlled by two factors essential for the development of the sympathetic nervous system and provide in vivo regulatory evidence to support previous findings that Hand2, rather than Hand1, is predominantly responsible for regulating TH, DBH, and Hand1 expression in developing sympathetic neurons. PMID- 22323724 TI - Dysmorphic photoreceptors in a P23H mutant rhodopsin model of retinitis pigmentosa are metabolically active and capable of regenerating to reverse retinal degeneration. AB - This study evaluated the capacity of Xenopus laevis retina to regenerate photoreceptor cells after cyclic light-mediated acute rod photoreceptor degeneration in a transgenic P23H mutant rhodopsin model of retinits pigmentosa. After discontinuation of cyclic light exposure, we monitored histologic progression of retinal regeneration over a 3 week recovery period. To assess their metabolomic states, contralateral eyes were processed for computational molecular phenotyping. We found that retinal degeneration in the P23H rhodopsin mutation could be partially reversed, with regeneration of rod photoreceptors recovering normal morphology (including full-length rod outer segments) by the end of the 3 week recovery period. In contrast, retinal degeneration mediated by directly induced apoptosis did not recover in the 3 week recovery period. Dystrophic rod photoreceptors with truncated rod outer segments were identified as the likely source of rod photoreceptor regeneration in the P23H retinas. These dystrophic photoreceptors remain metabolically active despite having lost most of their outer segments. PMID- 22323725 TI - Weak and nondiscriminative responses to conspecifics in the rat hippocampus. AB - Little is known about how hippocampal neurons in rodents respond to and represent conspecifics. To address this question, we let rats interact while quantifying hippocampal neuronal activation patterns with extracellular recordings and immediate-early gene (c-Fos) expression. A total of 319 single putative pyramidal neurons was recorded in dorsal hippocampus. In sessions with multiple stimulus rats, no cell responded differentially to individual rats (N = 267 cells). We did find, however, that the presence of other rats induced a significant enhancement or suppression of firing in a fraction of neurons (n = 22 of 319; 7%). As expected, a large fraction of neurons (n = 170; 53%) had place fields. There was no evidence for place-independent responses to rats. Rather, the modulations were linked to the spatial responses. While neurons did not discriminate between individual rats, they did discriminate between rats and inanimate objects. Surprisingly, neuronal responses were more strongly modulated by objects than by rats, even though subjects spent more time near their conspecifics. Consistent with the low fraction of rat-modulated cells, social encounters did not induce c Fos expression in the hippocampus, while there was a social interaction-specific expression in the basolateral amygdala. In both interacting and non-interacting rats, the fraction of c-Fos-expressing cells in the hippocampus was very low. Our investigation of social coding in the rat hippocampus, along with other recent work, showed that social responses were rare and lacked individual specificity, altogether speaking against a role of rodent dorsal hippocampus in social memory. PMID- 22323726 TI - Functional analysis of VPS41-mediated neuroprotection in Caenorhabditis elegans and mammalian models of Parkinson's disease. AB - Disruption of the lysosomal system has emerged as a key cellular pathway in the neurotoxicity of alpha-synuclein (alpha-syn) and the progression of Parkinson's disease (PD). A large-scale RNA interference (RNAi) screen using Caenorhabditis elegans identified VPS-41, a multidomain protein involved in lysosomal protein trafficking, as a modifier of alpha-syn accumulation and dopaminergic neuron degeneration (Hamamichi et al., 2008). Previous studies have shown a conserved neuroprotective function of human VPS41 (hVPS41) against PD-relevant toxins in mammalian cells and C. elegans neurons (Ruan et al., 2010). Here, we report that both the AP-3 (heterotetrameric adaptor protein complex) interaction domain and clathrin heavy-chain repeat domain are required for protecting C. elegans dopaminergic neurons from alpha-syn-induced neurodegeneration, as well as to prevent alpha-syn inclusion formation in an H4 human neuroglioma cell model. Using mutant C. elegans and neuron-specific RNAi, we revealed that hVPS41 requires both a functional AP-3 (heterotetrameric adaptor protein complex) and HOPS (homotypic fusion and vacuole protein sorting)-tethering complex to elicit neuroprotection. Interestingly, two nonsynonymous single-nucleotide polymorphisms found within the AP-3 interacting domain of hVPS41 attenuated the neuroprotective property, suggestive of putative susceptibility factors for PD. Furthermore, we observed a decrease in alpha-syn protein level when hVPS41 was overexpressed in human neuroglioma cells. Thus, the neuroprotective capacity of hVPS41 may be a consequence of enhanced clearance of misfolded and aggregated proteins, including toxic alpha-syn species. These data reveal the importance of lysosomal trafficking in maintaining cellular homeostasis in the presence of enhanced alpha syn expression and toxicity. Our results support hVPS41 as a potential novel therapeutic target for the treatment of synucleinopathies like PD. PMID- 22323727 TI - Neural broadening or neural attenuation? Investigating age-related dedifferentiation in the face network in a large lifespan sample. AB - Previous studies have found that cortical responses to different stimuli become less distinctive as people get older. This age-related dedifferentiation may reflect the broadening of the tuning curves of category-selective neurons (broadening hypothesis) or it may be due to decreased activation of category selective neurons (attenuation hypothesis). In this study, we evaluated these hypotheses in the context of the face-selective neural network. Over 300 participants, ranging in age from 20 to 89 years, viewed images of faces, houses, and control stimuli in a functional magnetic resonance imaging session. Regions within the core face network and extended face network were identified in individual subjects. Activation in many of these regions became significantly less face-selective with age, confirming previous reports of age-related dedifferentiation. Consistent with the broadening hypothesis, this dedifferentiation in the fusiform face area (FFA) was driven by increased activation to houses. In contrast, dedifferentiation in the extended face network was driven by decreased activation to faces, consistent with the attenuation hypothesis. These results suggest that age-related dedifferentiation reflects distinct processes in different brain areas. More specifically, dedifferentiation in FFA activity may be due to broadening of the tuning curves for face-selective neurons, while dedifferentiation in the extended face network reflects reduced face- or emotion-selective activity. PMID- 22323728 TI - Hemispheric asymmetry and visuo-olfactory integration in perceiving subthreshold (micro) fearful expressions. AB - Multisensory integration is ubiquitous, facilitating perception beyond the limit of individual senses. This mechanism is especially salient when individual sensory input is weak (i.e., the principle of inverse effectiveness), fusing subthreshold cues into tangible percepts. Nevertheless, it is unclear how this rule applies to threat perception, synthesizing elusive, discrete traces of a threat into a discernible danger signal. In light of hemispheric asymmetry in threat processing, we combined parafoveal stimulus presentation and the contralateral P1 visual event-related potential to investigate how aversive olfactory inputs enhance visual perception of highly degraded, subthreshold fearful expressions. The dominant right hemisphere exhibited early visual discrimination between subtle fear and neutral expressions, independently of accompanying odors. In the left hemisphere, differential visual processing occurred only at the convergence of negative odors and minute facial fear, highlighting the success and necessity of visuo-olfactory threat integration in this disadvantaged hemisphere. Reaction time data from a subsequent dot-detection task complemented these neural findings, revealing odor-dependent and hemisphere specific modulation of spatial attention to facial expressions. Our evidence thus indicates cross-modal threat integration in basic visual perception in humans that captures minimal threat information, especially in the blind right hemifield. Critically, this interaction between multisensory synergy and hemispheric asymmetry in threat perception may underlie the multifaceted fear experiences of everyday life. PMID- 22323729 TI - Ca2+/cAMP-sensitive covariation of I(A) and I(H) voltage dependences tunes rebound firing in dopaminergic neurons. AB - The level of expression of ion channels has been demonstrated to vary over a threefold to fourfold range from neuron to neuron, although the expression of distinct channels may be strongly correlated in the same neurons. We demonstrate that variability and covariation also apply to the biophysical properties of ion channels. We show that, in rat substantia nigra pars compacta dopaminergic neurons, the voltage dependences of the A-type (I(A)) and H-type (I(H)) currents exhibit a high degree of cell-to-cell variability, although they are strongly correlated in these cells. Our data also demonstrate that this cell-to-cell covariability of voltage dependences is sensitive to cytosolic cAMP and calcium levels. Finally, using dynamic clamp, we demonstrate that covarying I(A) and I(H) voltage dependences increases the dynamic range of rebound firing while covarying their amplitudes has a homeostatic effect on rebound firing. We propose that the covariation of voltage dependences of ion channels represents a flexible and energy-efficient way of tuning firing in neurons. PMID- 22323730 TI - Reduction of metabolic cost during motor learning of arm reaching dynamics. AB - It is often assumed that the CNS controls movements in a manner that minimizes energetic cost. While empirical evidence for actual metabolic minimization exists in locomotion, actual metabolic cost has yet to be measured during motor learning and/or arm reaching. Here, we measured metabolic power consumption using expired gas analysis, as humans learned novel arm reaching dynamics. We hypothesized that (1) metabolic power would decrease with motor learning and (2) muscle activity and coactivation would parallel changes in metabolic power. Seated subjects made horizontal planar reaching movements toward a target using a robotic arm. The novel dynamics involved compensating for a viscous curl force field that perturbed reaching movements. Metabolic power was measured continuously throughout the protocol. Subjects decreased movement error and learned the novel dynamics. By the end of learning, net metabolic power decreased by ~20% (~0.1 W/kg) from initial learning. Muscle activity and coactivation also decreased with motor learning. Interestingly, distinct and significant reductions in metabolic power occurred even after muscle activity and coactivation had stabilized and movement changes were small. These results provide the first evidence of actual metabolic reduction during motor learning and for a reaching task. Further, they suggest that muscle activity may not explain changes in metabolic cost as completely as previously thought. Additional mechanisms such as more subtle features of arm muscle activity, changes in activity of other muscles, and/or more efficient neural processes may also underlie the reduction in metabolic cost during motor learning. PMID- 22323731 TI - Remembering to learn: independent place and journey coding mechanisms contribute to memory transfer. AB - The neural mechanisms that integrate new episodes with established memories are unknown. When rats explore an environment, CA1 cells fire in place fields that indicate locations. In goal-directed spatial memory tasks, some place fields differentiate behavioral histories ("journey-dependent" place fields) while others do not ("journey-independent" place fields). To investigate how these signals inform learning and memory for new and familiar episodes, we recorded CA1 and CA3 activity in rats trained to perform a "standard" spatial memory task in a plus maze and in two new task variants. A "switch" task exchanged the start and goal locations in the same environment; an "altered environment" task contained unfamiliar local and distal cues. In the switch task, performance was mildly impaired, new firing maps were stable, but the proportion and stability of journey-dependent place fields declined. In the altered environment, overall performance was strongly impaired, new firing maps were unstable, and stable proportions of journey-dependent place fields were maintained. In both tasks, memory errors were accompanied by a decline in journey codes. The different dynamics of place and journey coding suggest that they reflect separate mechanisms and contribute to distinct memory computations. Stable place fields may represent familiar relationships among environmental features that are required for consistent memory performance. Journey-dependent activity may correspond with goal-directed behavioral sequences that reflect expectancies that generalize across environments. The complementary signals could help link current events with established memories, so that familiarity with either a behavioral strategy or an environment can inform goal-directed learning. PMID- 22323732 TI - Dissociation of response variability from firing rate effects in frontal eye field neurons during visual stimulation, working memory, and attention. AB - Recent studies suggest that trial-to-trial variability of neuronal spiking responses may provide important information about behavioral state. Observed changes in variability during sensory stimulation, attention, motor preparation, and visual discrimination suggest that variability may reflect the engagement of neurons in a behavioral task. We examined changes in spiking variability of frontal eye field (FEF) neurons in a change detection task requiring monkeys to remember a visually cued location and direct attention to that location while ignoring distracters elsewhere. In this task, the firing rates (FRs) of FEF neurons not only continuously reflect the location of the remembered cue and select targets, but also predict detection performance on a trial-by-trial basis. Changes in FEF response variability, as measured by the Fano factor (FF), showed clear dissociations from changes in FR. The FF declined in response to visual stimulation at all tested locations, even in the opposite hemifield, indicating much broader spatial tuning of the FF compared with the FR. Furthermore, despite robust spatial modulation of the FR throughout all epochs of the task, spatial tuning of the FF did not persist throughout the delay period, nor did it show attentional modulation. These results indicate that changes in variability, at least in the FEF, are most effectively driven by visual stimulation, while behavioral engagement is not sufficient. Instead, changes in variability may reflect shifts in the balance between feedforward and recurrent sources of excitatory drive. PMID- 22323733 TI - 5T4 glycoprotein regulates the sensory input-dependent development of a specific subtype of newborn interneurons in the mouse olfactory bulb. AB - Sensory input has been shown to regulate development in a variety of species and in various structures, including the retina, cortex, and olfactory bulb (OB). Within the mammalian OB specifically, the development of dendrites in mitral/tufted cells is well known to be odor-evoked activity dependent. However, little is known about the developmental role of sensory input in the other major OB population of the GABAgenic interneurons, such as granule cells and periglomerular cells. Here, we identified, with DNA microarray and in situ hybridization screenings, a trophoblast glycoprotein gene, 5T4, whose expression in a specific subtype of OB interneurons is dependent on sensory input. 5T4 is a type I membrane protein, whose extracellular domain contains seven leucine-rich repeats (LRR) flanked by characteristic LRR-N-flanking and C-flanking regions, and a cytoplasmic domain. 5T4 overexpression in the newborn OB interneurons facilitated their dendritic arborization even under the sensory input-deprived condition. By contrast, both 5T4 knockdown with RNAi and 5T4 knockout with mice resulted in a significant reduction in the dendritic arborization of 5T4(+) granule cells. Further, we identified the amino acid sequence in the 5T4 cytoplasmic domain that is necessary and sufficient for the sensory input dependent dendritic shaping of specific neuronal subtypes in the OB. Thus, these results demonstrate that 5T4 glycoprotein contributes in the regulation of activity-dependent dendritic development of interneurons and the formation of functional neural circuitry in the OB. PMID- 22323734 TI - Nicotine-induced upregulation of native neuronal nicotinic receptors is caused by multiple mechanisms. AB - Nicotine causes changes in brain nicotinic acetylcholine receptors (nAChRs) during smoking that initiate addiction. Nicotine-induced upregulation is the long lasting increase in nAChR radioligand binding sites in brain resulting from exposure. The mechanisms causing upregulation are not established. Many different mechanisms have been reported with the assumption that there is a single underlying cause. Using live rat cortical neurons, we examined for the first time how exposure and withdrawal of nicotine shape the kinetics of native alpha4beta2 containing nAChR upregulation in real time. Upregulation kinetics demonstrates that at least two different mechanisms underlie this phenomenon. First, a transient upregulation occurs that rapidly reverses, faster than nAChR degradation, and corresponds to nAChR conformational changes as assayed by conformational-dependent, subunit-specific antibodies. Second, a long-lasting process occurs correlating with increases in nAChR numbers caused by decreased proteasomal subunit degradation. Previous radioligand binding measurements to brain tissue have measured the second process and largely missed the first. We conclude that nicotine-induced upregulation is composed of multiple processes occurring at different rates with different underlying causes. PMID- 22323735 TI - Influence of reconstruction parameters during filtered backprojection and ordered subset expectation maximization in the measurement of the left-ventricular volumes and function during gated SPECT. AB - A crucial method for investigating patients with coronary artery disease (CAD) is the calculation of the left ventricular ejection fraction (LVEF). It is, consequently, imperative to precisely estimate the value of LVEF--a process that can be done with myocardial perfusion scintigraphy. Therefore, the present study aimed to establish and compare the estimation performance of the quantitative parameters of the reconstruction methods filtered backprojection (FBP) and ordered-subset expectation maximization (OSEM). METHODS: A beating-heart phantom with known values of end-diastolic volume, end-systolic volume, and LVEF was used. Quantitative gated SPECT/quantitative perfusion SPECT software was used to obtain these quantitative parameters in a semiautomatic mode. The Butterworth filter was used in FBP, with the cutoff frequencies between 0.2 and 0.8 cycles per pixel combined with the orders of 5, 10, 15, and 20. Sixty-three reconstructions were performed using 2, 4, 6, 8, 10, 12, and 16 OSEM subsets, combined with several iterations: 2, 4, 6, 8, 10, 12, 16, 32, and 64. RESULTS: With FBP, the values of end-diastolic, end-systolic, and the stroke volumes rise as the cutoff frequency increases, whereas the value of LVEF diminishes. This same pattern is verified with the OSEM reconstruction. However, with OSEM there is a more precise estimation of the quantitative parameters, especially with the combinations 2 iterations * 10 subsets and 2 iterations * 12 subsets. CONCLUSION: The OSEM reconstruction presents better estimations of the quantitative parameters than does FBP. This study recommends the use of 2 iterations with 10 or 12 subsets for OSEM and a cutoff frequency of 0.5 cycles per pixel with the orders 5, 10, or 15 for FBP as the best estimations for the left ventricular volumes and ejection fraction quantification in myocardial perfusion scintigraphy. PMID- 22323736 TI - ApoE-directed therapeutics rapidly clear beta-amyloid and reverse deficits in AD mouse models. AB - Alzheimer's disease (AD) is associated with impaired clearance of beta-amyloid (Abeta) from the brain, a process normally facilitated by apolipoprotein E (apoE). ApoE expression is transcriptionally induced through the action of the nuclear receptors peroxisome proliferator-activated receptor gamma and liver X receptors in coordination with retinoid X receptors (RXRs). Oral administration of the RXR agonist bexarotene to a mouse model of AD resulted in enhanced clearance of soluble Abeta within hours in an apoE-dependent manner. Abeta plaque area was reduced more than 50% within just 72 hours. Furthermore, bexarotene stimulated the rapid reversal of cognitive, social, and olfactory deficits and improved neural circuit function. Thus, RXR activation stimulates physiological Abeta clearance mechanisms, resulting in the rapid reversal of a broad range of Abeta-induced deficits. PMID- 22323737 TI - Intensifying weathering and land use in Iron Age Central Africa. AB - About 3000 years ago, a major vegetation change occurred in Central Africa, when rainforest trees were abruptly replaced by savannas. Up to this point, the consensus of the scientific community has been that the forest disturbance was caused by climate change. We show here that chemical weathering in Central Africa, reconstructed from geochemical analyses of a marine sediment core, intensified abruptly at the same period, departing substantially from the long term weathering fluctuations related to the Late Quaternary climate. Evidence that this weathering event was also contemporaneous with the migration of Bantu speaking farmers across Central Africa suggests that human land-use intensification at that time had already made a major impact on the rainforest. PMID- 22323738 TI - Plant UVR8 photoreceptor senses UV-B by tryptophan-mediated disruption of cross dimer salt bridges. AB - The recently identified plant photoreceptor UVR8 (UV RESISTANCE LOCUS 8) triggers regulatory changes in gene expression in response to ultraviolet-B (UV-B) light through an unknown mechanism. Here, crystallographic and solution structures of the UVR8 homodimer, together with mutagenesis and far-UV circular dichroism spectroscopy, reveal its mechanisms for UV-B perception and signal transduction. beta-propeller subunits form a remarkable, tryptophan-dominated, dimer interface stitched together by a complex salt-bridge network. Salt-bridging arginines flank the excitonically coupled cross-dimer tryptophan "pyramid" responsible for UV-B sensing. Photoreception reversibly disrupts salt bridges, triggering dimer dissociation and signal initiation. Mutation of a single tryptophan to phenylalanine retunes the photoreceptor to detect UV-C wavelengths. Our analyses establish how UVR8 functions as a photoreceptor without a prosthetic chromophore to promote plant development and survival in sunlight. PMID- 22323739 TI - Public health and biosecurity. The obligation to prevent the next dual-use controversy. PMID- 22323740 TI - The alarmin interleukin-33 drives protective antiviral CD8+ T cell responses. AB - Pathogen-associated molecular patterns decisively influence antiviral immune responses, whereas the contribution of endogenous signals of tissue damage, also known as damage-associated molecular patterns or alarmins, remains ill defined. We show that interleukin-33 (IL-33), an alarmin released from necrotic cells, is necessary for potent CD8(+) T cell (CTL) responses to replicating, prototypic RNA and DNA viruses in mice. IL-33 signaled through its receptor on activated CTLs, enhanced clonal expansion in a CTL-intrinsic fashion, determined plurifunctional effector cell differentiation, and was necessary for virus control. Moreover, recombinant IL-33 augmented vaccine-induced CTL responses. Radio-resistant cells of the splenic T cell zone produced IL-33, and efficient CTL responses required IL-33 from radio-resistant cells but not from hematopoietic cells. Thus, alarmin release by radio-resistant cells orchestrates protective antiviral CTL responses. PMID- 22323741 TI - Triggering a cell shape change by exploiting preexisting actomyosin contractions. AB - Apical constriction changes cell shapes, driving critical morphogenetic events, including gastrulation in diverse organisms and neural tube closure in vertebrates. Apical constriction is thought to be triggered by contraction of apical actomyosin networks. We found that apical actomyosin contractions began before cell shape changes in both Caenorhabitis elegans and Drosophila. In C. elegans, actomyosin networks were initially dynamic, contracting and generating cortical tension without substantial shrinking of apical surfaces. Apical cell cell contact zones and actomyosin only later moved increasingly in concert, with no detectable change in actomyosin dynamics or cortical tension. Thus, apical constriction appears to be triggered not by a change in cortical tension, but by dynamic linking of apical cell-cell contact zones to an already contractile apical cortex. PMID- 22323742 TI - Syndrome of inappropriate secretion of antidiuretic hormone in traumatic brain injury: when tolvaptan becomes a life saving drug. AB - OBJECTIVE: To outline the role of a new drug, tolvaptan, in treating severe and chronic hyponatraemia. Tolvaptan decreases aquaporin expression in renal collecting ducts, by inhibiting antidiuretic hormone (ADH)-V2 receptors, to promote free water clearance. Given its mechanism of action, this drug seems the ideal treatment for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) when the osmotic imbalance leads to life threatening complications. DATA SOURCES: A case is described of severe hyponatraemia deriving from SIADH secondary to meningoencephalitis in a patient admitted to hospital for traumatic brain injury. DATA EXTRACTION: Clinical, laboratory and radiological data at presentation and for a 1 year of follow-up were analysed. DATA SYNTHESIS: Tolvaptan ameliorated hyponatraemia, brain oedema and consciousness, and drug withdrawal led to recurrence of hyponatraemia and coma. CONCLUSIONS: In patients with SIADH, which is not self-limited, and is associated with severe cognitive impairment, the use Tolvaptan may prove life saving and should be rigorously evaluated. PMID- 22323743 TI - The LRRK2 G2019S mutation is associated with Parkinson disease and concomitant non-skin cancers. AB - OBJECTIVE: In view of the fact that cancer patterns in patients with Parkinson disease (PD) differ from the general population, we aimed to verify whether patients with PD with LRRK2 mutations have an increased risk for particular cancer types. METHODS: In this cross-sectional study, eligible consenting Jewish patients with PD were genotyped for the predominant LRRK2 G2019S mutation. Oncologic data were obtained by personal interview and reviewing patients' files. Stepwise logistic regression was applied to model the probability of cancer occurrence in carriers vs noncarriers. RESULTS: Overall, 79/490 (16.1%) genotyped patients carried the G2019S mutation. Seventy-seven (16%) were diagnosed with cancer; of those, 67 (14%) with a non-skin cancer. Eighteen (23%) carriers vs 49 (12%) noncarriers had a non-skin cancer (p = 0.01, odds ratio [OR] = 2.18, 95% confidence interval [CI] 1.19-3.99). A significant ethnicity effect was noted (p = 0.045, OR = 1.84, 95% CI 1.02-3.34). Among Ashkenazi patients, age and LRRK2 emerged as significant using stepwise logistic regression including age, gender, and LRRK2 status as explanatory variables. The OR for LRRK2 mutation carriers adjusted for age was 3.38 (95% CI 1.64-6.97, p = 0.0009). CONCLUSIONS: Ashkenazi Jewish patients with PD who harbor the G2019S LRRK2 mutation are more likely to have a concomitant non-skin cancer than noncarriers. PMID- 22323744 TI - Genotype-phenotype relationship in 2 SMA III patients with novel mutations in the Tudor domain. AB - OBJECTIVE: We report the cases of 2 patients with late-onset spinal muscular atrophy (SMA) type III, who were hemizygous for SMN1 deletion and carriers of novel SMN1 intragenic missense mutations, and we investigate the genotype phenotype relationship. METHODS: Patients were tested for SMN1 deletions with standard methodology. Sequencing of all exons, exon-intron junctions, and flanking sequences of SMN1 by nested PCR was used to detect intragenic point mutations. SMN1 and SMN2 quantification was undertaken to investigate the genotype-phenotype relationship. RESULTS: Two novel point mutations were identified in exon 3 of SMN1 (p.Tyr130Cys and p.Tyr130His) in the highly conserved Tudor domain of the Smn protein. CONCLUSIONS: The genetic basis of SMA in the rare cases of compound heterozygous carriers of SMN1 deletions is complex. Small intragenic SMN1 mutations often lead to severe SMA phenotypes, especially if the point mutations lie in exon 3 that codes for the highly conserved Tudor domain of the Smn protein. Although both our patients were carriers of intragenic SMN1 mutations in the coding region of the Tudor domain, they presented with a mild SMA phenotype despite a low SMN2 copy number. We discuss the possible determinant role of these novel missense mutations in the phenotypic outcome and compensatory mechanisms that may account for the genotype-phenotype discrepancy. PMID- 22323745 TI - Parkinson disease, cancer, and LRRK2: causation or association? PMID- 22323746 TI - Chitinase enzyme activity in CSF is a powerful biomarker of Alzheimer disease. AB - OBJECTIVE: DNA damage accumulation in brain is associated with the development of Alzheimer disease (AD), but newly identified protein markers of DNA damage have not been evaluated in the diagnosis of AD and other forms of dementia. METHODS: Here, we analyzed the level of novel biomarkers of DNA damage and telomere dysfunction (chitinase activity, N-acetyl-glucosaminidase activity, stathmin, and EF-1alpha) in CSF of 94 patients with AD, 41 patients with non-AD dementia, and 40 control patients without dementia. RESULTS: Enzymatic activity of chitinase (chitotriosidase activity) and stathmin protein level were significantly increased in CSF of patients with AD and non-AD dementia compared with that of no dementia control patients. As a single marker, chitinase activity was most powerful for distinguishing patients with AD from no dementia patients with an accuracy of 85.8% using a single threshold. Discrimination was even superior to clinically standard CSF markers that showed an accuracy of 78.4% (beta-amyloid) and 77.6% (tau). Combined analysis of chitinase with other markers increased the accuracy to a maximum of 91%. The biomarkers of DNA damage were also increased in CSF of patients with non-AD dementia compared with no dementia patients, and the new biomarkers improved the diagnosis of non-AD dementia as well as the discrimination of AD from non-AD dementia. CONCLUSIONS: Taken together, the findings in this study provide experimental evidence that DNA damage markers are significantly increased in AD and non-AD dementia. The biomarkers identified outperformed the standard CSF markers for diagnosing AD and non-AD dementia in the cohort investigated. PMID- 22323747 TI - A randomized trial of varenicline (Chantix) for the treatment of spinocerebellar ataxia type 3. AB - OBJECTIVE: The objective of this double-blind, placebo-controlled, randomized study was to evaluate the efficacy of varenicline (Chantix), a partial agonist at alpha4beta2 neuronal nicotinic acetylcholine receptors used for smoking cessation, in patients with spinocerebellar ataxia (SCA) 3. METHODS: Patients with genetically confirmed SCA3 were randomly assigned to receive either varenicline (4 weeks for titration and 4 weeks at a dose of 1 mg twice daily) or placebo. Outcome measures included changes in the Scale for the Rating and Assessment of Ataxia (SARA) scores at endpoint (8 weeks) compared with baseline, a timed 25-foot walk and 9-hole peg test, measurements of mood and anxiety, and adverse events. RESULTS: Twenty patients with SCA3 (mean age = 51 +/- 10.98 years; mean disease duration = 14 +/- 9.82 years; mean SARA score = 16.13 +/- 4.67) were enrolled in the study, and data on 18 patients were analyzed in period I. The most common side effect associated with varenicline was nausea. Improvements were noted in the SARA subsections for gait (p = 0.04), stance (p = 0.03), rapid alternating movements (p = 0.003), and timed 25-foot walk (p = 0.05) and Beck Depression Inventory scores (p = 0.03) in patients taking varenicline compared with those taking placebo at endpoint, with a trend toward improvement in the SARA total score (p = 0.06) in the varenicline group. CONCLUSIONS: In this controlled study, varenicline significantly improved axial symptoms and rapid alternating movements in patients with SCA3 as measured by SARA subscores and was fairly well tolerated. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that varenicline improved the axial functions of gait, stance, and timed 25-foot walk but did not improve appendicular function, except for rapid alternating movements, in adult patients with genetically confirmed SCA3. PMID- 22323748 TI - Role of DaTSCAN and clinical diagnosis in Parkinson disease. AB - OBJECTIVE: To assess the role of DaTSCAN in the diagnosis of Parkinson disease (PD). METHODS: Using the sensitivity and specificity values obtained in the 2 studies that recently led the US Food and Drug Administration to approve the use of DaTSCAN for the diagnosis of PD, calculations were carried out to estimate the accuracy of the clinical diagnosis taking DaTSCAN findings as the standard of truth. RESULTS: In early PD, a clinical diagnosis of "possible" or "probable" PD has a sensitivity of 98% and a specificity of 67%. The specificity increases to 94% once the clinical diagnosis becomes established. The overall accuracy of the clinical diagnosis is 84% in early PD and 98% at later stages. The clinical diagnostic accuracy is mathematically identical to the diagnostic accuracy of DaTSCAN imaging. CONCLUSIONS: In the absence of neuropathologic validation, the overall accuracy of a clinical diagnosis of PD is very high and mathematically identical to the accuracy of DaTSCAN imaging, which calls into question the use of radiotracer neuroimaging as a diagnostic tool in clinical practice. PMID- 22323749 TI - The value of EEG monitoring after cardiac arrest treated with hypothermia. PMID- 22323750 TI - Domain-dependent clustering and genotype-phenotype analysis of LGI1 mutations in ADPEAF. AB - OBJECTIVE: In families with autosomal dominant partial epilepsy with auditory features (ADPEAF) with mutations in the LGI1 gene, we evaluated clustering of mutations within the gene and associations of penetrance and phenotypic features with mutation location and predicted effect (truncation or missense). METHODS: We abstracted clinical and molecular information from the literature for all 36 previously published ADPEAF families with LGI1 mutations. We used a sliding window approach to analyze mutation clustering within the gene. Each mutation was mapped to one of the gene's 2 major functional domains, N-terminal leucine-rich repeats (LRRs) and C-terminal epitempin (EPTP) repeats, and classified according to predicted effect on the encoded protein (truncation vs missense). Analyses of phenotypic features (age at onset and occurrence of auditory symptoms) in relation to mutation site and predicted effect included 160 patients with idiopathic focal unprovoked seizures from the 36 families. RESULTS: ADPEAF causing mutations clustered significantly in the LRR domain (exons 3-5) of LGI1 (p = 0.026). Auditory symptoms were less frequent in individuals with truncation mutations in the EPTP domain than in those with other mutation type/domain combinations (58% vs 80%, p = 0.018). CONCLUSION: The LRR region of the LGI1 gene is likely to play a major role in pathogenesis of ADPEAF. PMID- 22323751 TI - Does trans size matter in Huntington disease? PMID- 22323752 TI - Comment: Telomeres in AD--the long and the short of it. PMID- 22323753 TI - SMN1 gene duplications are associated with sporadic ALS. AB - OBJECTIVE: To investigate the role of SMN1 and SMN2 copy number variation and point mutations in amyotrophic lateral sclerosis (ALS) pathogenesis in a large population. METHODS: We conducted a genetic association study including 847 patients with ALS and 984 controls. We used multiplexed ligation-dependent probe amplification (MLPA) assays to determine SMN1 and SMN2 copy numbers and examined effects on disease susceptibility and disease course. Furthermore, we sequenced SMN genes to determine if SMN mutations were more prevalent in patients with ALS. A meta-analysis was performed with results from previous studies. RESULTS: SMN1 duplications were associated with ALS susceptibility (odds ratio [OR] 2.07, 95% confidence interval [CI] 1.34-3.20, p = 0.001). A meta-analysis with previous data including 3,469 individuals showed a similar effect: OR 1.85, 95% CI 1.18 2.90, p = 0.008). SMN1 deletions and SMN2 copy number status were not associated with ALS. SMN1 or SMN2 copy number variants had no effect on survival or the age at onset of the disease. We found no enrichment of SMN point mutations in patients with ALS. CONCLUSIONS: Our data provide firm evidence for a role of common SMN1 duplications in ALS, and raise new questions regarding the disease mechanisms involved. PMID- 22323754 TI - Solitary sclerosis: progressive myelopathy from solitary demyelinating lesion. AB - OBJECTIVE: To present a case series of patients with progressive myelopathy in the setting of a solitary demyelinating lesion. METHODS: We describe 7 patients evaluated over a 6-year period. All had progressive motor impairment attributable to an MRI lesion compatible with a demyelinating plaque in the brainstem or upper cervical spinal cord. At the time of evaluation, none met the International Panel imaging criteria for dissemination in space, and none described clinical symptoms consistent with relapses affecting other portions of the CNS. RESULTS: Lesions identified were in the ventral cervicomedullary junction in 4 patients, the ventral spinal cord in 2 patients, and the pons in 1 patient. Median age at onset was 43 years (range 33-51 years). Median follow-up interval was 3 years (range 2 27 years). Six patients reached an Expanded Disability Status Scale (EDSS) score of 6.0 or worse. Median time to EDSS score of 6.0 was 7.5 years (range 1.5-26 years). Four had CSF findings characteristic of multiple sclerosis (MS). None had CSF, imaging, or serologic evidence of an alternative etiology of progressive myelopathy. In 3 patients, serial MRI scans of the brain and spinal cord demonstrated no accumulation of lesions. Postmortem examination of a fourth patient demonstrated an isolated pontine demyelinating lesion. CONCLUSIONS: Solitary demyelinating lesions may produce a progressive myelopathy similar to primary progressive MS. Demyelinating disease should be in the differential diagnosis of progressive myelopathy despite absence of dissemination in space. PMID- 22323756 TI - More can be less: SMN1 gene duplications are associated with sporadic ALS. PMID- 22323757 TI - To scan or not to scan: DaT is the question. PMID- 22323758 TI - Early EEG correlates of neuronal injury after brain anoxia. AB - OBJECTIVES: EEG and serum neuron-specific enolase (NSE) are used for outcome prognostication in patients with postanoxic coma; however, it is unclear if EEG abnormalities reflect transient neuronal dysfunction or neuronal death. To assess this question, EEG abnormalities were correlated with NSE. Moreover, NSE cutoff values and hypothermic EEG features related with poor outcome were explored. METHODS: In a prospective cohort of 61 adults treated with therapeutic hypothermia (TH) after cardiac arrest (CA), multichannel EEG recorded during TH was assessed for background reactivity and continuity, presence of epileptiform transients, and correlated with serum NSE collected at 24-48 hours after CA. Demographic, clinical, and functional outcome data (at 3 months) were collected and integrated in the analyses. RESULTS: In-hospital mortality was 41%, and 82% of survivors had good neurologic outcome at 3 months. Serum NSE and EEG findings were strongly correlated (Spearman rho = 0.45; p < 0.001). Median NSE peak values were higher in patients with unreactive EEG background (p < 0.001) and discontinuous patterns (p = 0.001). While all subjects with nonreactive EEG died, 5 survivors (3 with good outcome) had NSE levels >33 MUg/L. CONCLUSION: The correlation between EEG during TH and serum NSE levels supports the hypothesis that early EEG alterations reflect permanent neuronal damage. Furthermore, this study confirms that absent EEG background reactivity and presence of epileptiform transients are robust predictors of poor outcome after CA, and that survival with good neurologic recovery is possible despite serum NSE levels> 33 MUg/L. This underscores the importance of multimodal assessments in this setting. PMID- 22323759 TI - Exceptional stroke-like episodes in a patient with type I autosomal angioedema. PMID- 22323760 TI - The prevalence of food insecurity is high and the diet quality poor in Inuit communities. AB - Indigenous peoples experience a disproportionate burden of food insecurity and the Arctic is no exception. We therefore evaluated the prevalence, socio demographic, and dietary correlates of food insecurity in the most comprehensive assessment of food insecurity in Arctic Canada. A cross-sectional survey of 1901 Inuit households was conducted in 2007-2008. Measurements included food insecurity, 24-h dietary recalls, socio-demographics, and anthropometry. Food insecurity was identified in 62.6% of households (95% CI = 60.3-64.9%) with 27.2% (95% CI = 25.1-29.3%) of households severely food insecure. The percent with an elevated BMI, waist circumference, and percent body fat was lower among individuals from food insecure households compared to food secure households (P <= 0.001). Adults from food insecure households had a significantly lower Healthy Eating Index score and consumed fewer vegetables and fruit, grains, and dairy products, and consumed a greater percent of energy from high-sugar foods than adults from food secure households (P <= 0.05). Food insecurity was associated with household crowding, income support, public housing, single adult households, and having a home in need of major repairs (P <= 0.05). The prevalence of having an active hunter in the home was lower in food insecure compared to food secure households (P <= 0.05). Food insecurity prevalence is high in Inuit communities, with implications for diet quality that over the long-term would be anticipated to exacerbate the risk of diet-related chronic diseases. Actions are required to improve food security that incorporate the traditional food system and healthy market food choices. PMID- 22323761 TI - Arginine and ornithine are the main precursors for citrulline synthesis in mice. AB - Recent isotopic tracer studies in mice, piglets, and humans have produced conflicting results as to the main carbon skeleton precursor for citrulline and arginine synthesis. This may be due in part to the different tracers infused and models used to interpret the stable isotope data. Furthermore, previous studies usually investigated a single precursor, which prevented the direct comparison among multiple precursors. To further elucidate the contribution of different precursors to citrulline synthesis, all possible enteral and plasma precursors of citrulline were studied in a mouse model during the postabsorptive and postprandial period using multitracer protocols. In addition, three different models were used to interpret the stable isotope data. The utilization of the classic precursor-product equation, developed for i.v. infused tracers but also used to include i.g. tracers, grossly overestimated the contribution of enteral precursors. Regardless of the model employed, dietary and plasma arginine were the main precursors for citrulline synthesis during feeding and plasma arginine during feed deprivation. The contribution of arginine was directly at the site of citrulline synthesis and through plasma ornithine. The predominant role of arginine and ornithine seen in this study supports the observations in mice, piglets, and humans suggesting that ornithine amino transferase is a pivotal enzyme in this pathway. PMID- 22323762 TI - A wax ester and astaxanthin-rich extract from the marine copepod Calanus finmarchicus attenuates atherogenesis in female apolipoprotein E-deficient mice. AB - The aim of this study was to investigate the effect of dietary supplementation with an oil extracted from the zooplankton copepod Calanus finmarchicus [calanus oil (CO)] on atherosclerosis in apoE-deficient (apoE(-/-)) mice. Thirty 6-wk-old female apoE(-/-) mice (n = 10/group) were fed: 1) a Western-type, high-fat diet (HFD); 2) HFD supplemented with 1% (wt:wt) CO; or 3) HFD supplemented with 0.88% (wt:wt) corn oil + 0.12% (wt:wt) EPA+DHA ethyl esters (EPA+DHA) for 13 wk. Dietary CO supplementation lowered total aorta atherogenesis by 36.5% compared to the HFD (P < 0.01), whereas the reduction in the lesion prone aortic arch was 34.8% (P < 0.01). The degree of aortic atherogenesis was intermediate in mice fed EPA+DHA compared to those fed HFD and CO. The effect on atherogenesis was paralleled by reduced expression of hepatic genes for the proinflammatory cytokines, Ccl2, Icam1, Il1b, and Nfkb1, in mice fed CO compared to those fed HFD. For mice fed EPA+DHA, gene expression did not differ compared to those fed CO or HFD. Plasma concentrations of total cholesterol, TG, and cytokines did not differ between the groups at the end of the study. However, mice fed CO gained more weight compared to those fed HFD but not compared to those fed EPA+DHA. In conclusion, dietary CO supplementation attenuated atherosclerotic lesion formation in female apoE(-/-) mice and may be an effective and safe dietary intervention to reduce the development of atherosclerosis. However, further studies are warranted to elucidate the underlying physiological and molecular mechanisms. PMID- 22323763 TI - The omega-3 fatty acid nutritional landscape: health benefits and sources. AB - Dietary fatty acids (FA) are increasingly recognized as major biologic regulators and have properties that relate to health outcomes and disease. The longer chain, more bioactive (n-6) (or omega-6) FA and (n-3) (or omega-3) FA share similar elongation and desaturation enzymes in their conversion from the essential (n-6) FA, linoleic acid, and (n-3) FA, alpha-linolenic acid (ALA). Conversion from these essential FA is very inefficient. However, now for the (n-3) FA series, soy oil can be enriched with (n-3) stearidonic acid (SDA) to allow for much more efficient conversion to longer chain EPA. EPA and the longer chain DHA possess distinct physical and biological properties that generally impart properties to cells and tissue, which underlie their ability to promote health and prevent disease. Although active in a number of areas of human biology, mechanisms of action of EPA and DHA are perhaps best defined in cardiovascular disease. There is concern that to reach the intake recommendations of EPA and DHA, their supply from cold water fish will be insufficient. Gaps in understanding mechanisms of action of (n-3) FA in a number of health and disease areas as well as optimal sources and intake levels for each need to be defined by further research. Because of the inefficient conversion of ALA, the appearance of SDA in enriched soy oil offers a biologically effective and cost effective approach to providing a sustainable plant source for (n-3) FA in the future. PMID- 22323765 TI - Consumption of potentially fortifiable foods by women and young children varies by ecological zone and socio-economic status in Cameroon. AB - In preparation for a proposed large-scale food fortification program in Cameroon, we completed a nationally representative, cross-sectional, cluster survey to assess the consumption patterns of four potentially fortifiable foods (refined vegetable oil, wheat flour, sugar, and bouillon cube) by women and children. Thirty clusters were randomly chosen in each of three ecologic zones (south, north, and large cities) and 10 households (HH) per cluster were selected, each with a child 12-59 mo old and a primary female caregiver 15-49 y old (total 1002 HH). Blood samples were collected and food consumption was assessed by FFQ and 24 h dietary recall. Anemia (39% of women, 58% of children) and deficiencies of iron (15-32%, 21-70%), zinc (77%, 70%), vitamin A (22%, 35%), and vitamin B-12 (28%, 27%) were common, especially in the north and among HH with lower socio-economic status (SES). Oil was consumed by 54% of HH, whereas >75% of HH consumed wheat flour, sugar, and bouillon cube. For most foods, coverage was lower among HH with lower SES. On average, oil, wheat flour, and sugar were consumed once per day and bouillon cube was consumed twice per day. Median intakes of oil, wheat flour, sugar, and bouillon cube (among consumers) were 19.8, 79.4, 30.0, and 1.9 g/d for women and 12.0, 49.4, 19.4, and 0.9 g/d for children, respectively. Food consumption patterns of high risk population subgroups must be considered, along with technical feasibility and cost, for the selection of appropriate vehicles for food fortification. PMID- 22323766 TI - Serum 25-hydroxyvitamin D concentrations and prevalence estimates of hypovitaminosis D in the U.S. population based on assay-adjusted data. AB - Prevalence of hypovitaminosis D from previous NHANES reports did not account for assay changes and drifts over time. Thus, published NHANES reports on vitamin D status for the U.S. population were likely either over- or underestimated. We investigated changes in vitamin D status in the U.S. using assay-adjusted serum 25-hydroxyvitamin D [25(OH)D] data from NHANES, 1988-1994 (n = 18,641) and three cycles of NHANES, 2001-2006 (n = 23,424). Changes in geometric mean serum 25(OH)D and prevalence estimates for various serum 25(OH)D cut points (<25, <30, <40, <50, and <75 nmol/L) were determined. From 1988-1994 to 2001-2006, geometric mean serum 25(OH)D significantly decreased by 9% in all participants, 12% in men, 14% in blacks, 16% in 12- to 15-y-old adolescents, 16% in 20- to 30-y-old adults, 13% in nonsupplement users, and 12% in persons with BMI >80th percentile (P < 0.001). From 1988-1994 to 2001-2006, prevalence of serum 25(OH)D <30 nmol/L increased from 5 to 10% in all participants, from 3 to 8% in men, from 22 to 38% in blacks, from 3 to 8% in 12- to 15-y-old adolescents, from 5 to 12% in 20- to 30-y-old adults, from 6 to 14% in nonsupplement users, and from 8 to 17% in persons with BMI >80th percentile (P < 0.001). Previous NHANES reports overestimated the increase in prevalence of hypovitaminosis D. The recent decline in vitamin D status in the U.S. is more likely due to increased prevalence of obesity and other lifestyle changes but not to changes in milk consumption. PMID- 22323755 TI - CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion. AB - OBJECTIVE: Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs. METHODS: We modeled natural log transformed age at onset as a function of CAG repeat lengths of expanded and normal alleles and their interaction by linear regression. RESULTS: An apparently significant effect of interaction on age at motor onset among 4,068 subjects was dependent on a single outlier data point. A rigorous statistical analysis with a well-behaved dataset that conformed to the fundamental assumptions of linear regression (e.g., constant variance and normally distributed error) revealed significance only for the expanded CAG repeat, with no effect of the normal CAG repeat. Ten subjects with 2 expanded alleles showed an age at motor onset consistent with the length of the larger expanded allele. CONCLUSIONS: Normal allele CAG length, interaction between expanded and normal alleles, and presence of a second expanded allele do not influence age at onset of motor manifestations, indicating that the rate of HD pathogenesis leading to motor diagnosis is determined by a completely dominant action of the longest expanded allele and as yet unidentified genetic or environmental factors. PMID- 22323767 TI - Conclusions and recommendations from the symposium, Heart Healthy Omega-3s for Food: Stearidonic Acid (SDA) as a Sustainable Choice. AB - Faculty who had presented at the symposium "Heart Healthy Omega-3s (n-3 fatty acids) for Food: Stearidonic Acid (SDA) as a Sustainable Choice" met and agreed upon conclusions and recommendations that could be made on the basis of evidence provided at the symposium. The participants also submitted manuscripts relating to their topics and these are presented in this supplement. These manuscripts were reviewed and also contributed to the conclusions and recommendations presented herein. The three major objectives of the symposium were to: 1) increase understanding of the current and emerging knowledge regarding the health benefits of (n-3) fatty acids (FA) including a focus on stearidonic acid (SDA) and EPA; 2) evaluate the importance of increasing (n-3) FA consumption in the US and the current challenge of doing so via mainstream foods; and 3) consider the health and food application benefits of SDA as a precursor to EPA and a plant based sustainable source of highly unsaturated (n-3) FA for mainstream foods. Specific areas for future research were defined and included in the summary and conclusions herein. Overall evidence-based conclusions included: the current evidence provides a strong rationale for increasing (n-3) FA intakes in the US and other populations; current consumption of (n-3) FA in most populations is either insufficient or not efficient at providing adequate tissue levels of the long-chain (n-3) FA EPA and DHA; SDA in soybean oil appears to be a cost effective and sustainable plant-based source that could contribute to reaching recommended levels of (n-3) FA intake, but more research and surveillance is needed; and adding SDA-enriched soybean oil to foods should be considered as a natural fortification approach to improving (n-3) FA status in the US and other populations. References for these conclusions and recommendations can be found in the articles included in the supplement. PMID- 22323768 TI - Epigallocatechin-3-gallate inhibits expression of receptors for T cell regulatory cytokines and their downstream signaling in mouse CD4+ T cells. AB - We previously showed a suppressive effect of epigallocatechin-3-gallate (EGCG) on T cell cycling and expansion as well as a paradoxical effect on IL-2 levels (upregulating) and IL-2 receptor (IL-2R)alpha expression (downregulating). Thus, in the current study, we tested the hypothesis that EGCG affects T cell responses via impairing the IL-2/IL-2R signaling. We found that EGCG inhibited anti CD3/CD28-induced proliferation of naive CD4(+) T cells from C57BL/6 mice. EGCG increased accumulation of IL-2 but inhibited expression of IL-2R, including all its subunits [IL-2Ralpha, IL-2/IL-15Rbeta, and common gamma chain (gammac)]. Using phosphorylation of STAT5 as a marker, we further found that EGCG suppressed IL-2R downstream signaling. Because IL-2R subunits IL-2/IL-15Rbeta- and gammac are shared with IL-15R and gammac is shared with IL-7R, we suspected that EGCG might also influence the signaling of IL-15 and IL-7, the two key regulators in maintaining T cell homeostasis. Results showed that EGCG suppressed IL-15 and IL 7 signaling; further, EGCG not only inhibited the subunits in IL-15R and IL-7R shared with IL-2R, but also affected their proprietary alpha chains in a manner that aligns with an impaired signaling. Although IL-2, IL-15, and IL-7 have separate and distinctive roles in regulating T cells, all of them are critical for T cell survival, expansion, and differentiation. Thus, these findings indicate an involvement of T cell growth cytokines in EGCG-induced T cell suppression through downregulated expression of their receptors and downstream signaling. This implies a potential application in controlling dysregulated T cell functions such as those observed in autoimmune and inflammatory disorders. PMID- 22323769 TI - Analysis of two L-Galactono-1,4-lactone-responsive genes with complementary expression during the development of Arabidopsis thaliana. AB - Unraveling the role of genes annotated as protein of unknown function is of importance in progression of plant science. l-Galactono-1,4-lactone (l-GalL) is the terminal precursor for ascorbic acid (AsA) biosynthesis in Arabidopsis thaliana, and a previous study showed two DUF (domains of unknown function) 642 family genes (At1g80240 and At5g25460, designated as DGR1 and DGR2, respectively) to be sensitive to it. In this work, leaves from wild-type Arabidopsis were fed with d-glucose, l-galactose, l-GalL and AsA, and the expression level of the At1g80240 and At5g25460 genes showed a specific response to l-GalL, but not to the other supplements despite the increases of the tissue AsA contents. Analysis of promoter-beta-glucuronidase (GUS) transgenic plants showed the two genes to be complementarily expressed at the root apex and in the rest of the root excluding the apex, respectively, in both young and old seedlings, and to be expressed at the leaf primordia. The GUS activity under the control of the At5g25460 promoter was high in the cotyledon and leaf veins of young seedlings. These findings were consistent with the results of quantitative real-time PCR. Interestingly, the T DNA insertion mutant of At5g25460 (SALK_125079) displayed shorter roots and smaller rosettes than Col-0; however, no phenotypic difference was observed between the T-DNA insertion mutant of At1g80240 and the wild type. This is the first report on the expression and functional analysis of these two DUF642 family genes, with the results revealing the contribution of DGR genes to the development of Arabidopsis. PMID- 22323770 TI - Malformed selenoproteins are removed by the ubiquitin--proteasome pathway in Stanleya pinnata. AB - Despite the widely accepted belief that selenium toxicity in plants is manifested by the misincorporation of selenocysteine into selenoproteins, there is a lack of data suggesting that selenoproteins are malformed or misfolded. Plant mechanisms to prevent the formation of selenoproteins are associated with increased selenium tolerance, yet there is no evidence to suggest that selenoproteins are malformed or potentially misfolded. We reasoned that if selenoproteins are malformed, then they might be degraded by the ubiquitin-proteasome pathway. The data demonstrate that selenate treatment induced the accumulation of both oxidized and ubiquitinated proteins, thus implicating both the 20S and 26S proteasome of Stanleya pinnata, a selenium-hyperaccumulating plant, in a selenate response. Inhibition of the proteasome increases the amount of selenium incorporated into protein, but not other elements. Furthermore, a higher percentage of selenium was found in a ubiquitinated protein fraction compared with other elements, suggesting that malformed selenoproteins are preferentially ubiquitinated and removed by the proteasome. Additionally, levels of the 20S and 26S proteasome and two heat shock proteins increase upon selenate treatment. Arabidopsis mutants with defects in the 26S proteasome have decreased selenium tolerance, which further supports the hypothesis that the 26S proteasome probably prevents selenium toxicity by removing selenoproteins. PMID- 22323771 TI - Impact commentaries. Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays. PMID- 22323772 TI - Perspectives on molecular targeted therapies and clinical trials for neurodegenerative diseases. AB - Recent advancements in neurobiology have provided increasing insights into the pathophysiology of neurodegenerative diseases, and opened doors to the development of molecular targeted therapies. Although many compounds showed positive results in animal studies, there is almost no drug for which the efficacy has been confirmed in clinical trials. This failure reflects a number of unsolved problems: limited knowledge of the exact pathways of neuron loss; safety and delivery issues of compounds; lack of established animal models that faithfully recapitulate human pathology; lack of validated, sensitive outcome measures; and limited tools to diagnose pre-symptomatic patients. To investigate the efficacy of potential disease modifying agents with limited financial and patient resources, the efficiency of both basic and clinical studies should be improved by integrated approaches. The reproduction of positive results from animal experiments that analyse the efficacy of compounds at symptomatic stages is needed to improve the credibility of preclinical studies. To effectuate proof of concept processes, novel designs of phase 2 clinical trials, such as the futility study, are being developed. Given the modest effects of molecular targeted therapies in human, it is necessary to explore clinical outcome measures that are resistant to variability, subjectivity and placebo. Furthermore, there is an increasing need for testing interventions before the onset of symptoms. Analyses of natural histories of biological and neurophysiological markers may provide indispensable information for designing such preventive trials. As it is now clear that conventional approaches are not necessarily appropriate for the development of molecular targeted therapies, both basic and clinical studies require conceptual innovation. PMID- 22323773 TI - Experimental radionuclide therapy of HER2-expressing xenografts using two-step targeting nuclisome particles. AB - The therapeutic potential of Auger-electron emitting radionuclides is strongly dependent on their close vicinity to DNA, since the energy deposition is mainly localized within a few cubic nanometers around the site of decay. Thus, apart from specificity, successful tumor therapy relies on a nuclear delivery strategy. We recently presented a two-step targeting strategy to transport Auger-electron emitting radionuclides into the cell nucleus by means of nuclide-filled liposomes (Nuclisome particles), that is, polyethylene glycol-stabilized, tumor-cell targeting liposomes loaded with (125)I-labeled anthracyclines. In the present study, the survival of mice intraperitoneally inoculated with human HER2 expressing SKOV-3 tumor cells and treated with HER2-targeting Nuclisome particles was studied. METHODS: BALB/c nu/nu mice were inoculated with 10(7) SKOV-3 cells intraperitoneally and thereafter directly injected with Nuclisome particles with increasing specific radioactivity. Groups of 10-12 mice were treated with 0.01 MBq/mouse up to 2 MBq/mouse, and survival was monitored and compared with that in control groups (n = 33). Organs were analyzed for HER2 expression and radiotoxic effects histologically. Absorbed doses were estimated using dose factors from the online Radiation Dose Assessment Resource model. RESULTS: The results showed a clear correlation between administered radioactive dose and survival. No such dose-dependent survival was observed for mice treated with Nuclisome particles lacking HER2-targeting ability. With HER2-targeting Nuclisome particles, a significant increase in survival, compared with that of untreated control mice, could already be seen at an administered activity of 0.1 MBq/mouse (P = 0.0301). At the highest activity administered, 2 MBq/mouse (P < 0.0001), 70% of the mice survived the study and most were tumor-free. Neither macroscopic nor microscopic radiotoxic side effects were observed. Dosimetric calculations, assuming nonreceptor targeting, revealed that the radioactive doses to normal tissues were low. CONCLUSION: Taken together the results show that with successful targeting to the tumor-cell nucleus it is possible to obtain a therapeutic effect from Auger-electron-emitting radionuclides administered at radioactive doses low enough to spare normal tissue from radiotoxic side effects. PMID- 22323774 TI - 18F-FEAnGA for PET of beta-glucuronidase activity in neuroinflammation. AB - Activation of microglia is a hallmark of inflammatory, infectious, and degenerative diseases of the central nervous system. Several studies have indicated that there is an increase in release of beta-glucuronidase by activated microglia into the extracellular space at the site of neuroinflammation. beta glucuronidase is involved in the hydrolysis of glycosaminoglycans on the cell surface and the degradation of the extracellular matrix. Therefore, beta glucuronidase might be a biomarker for ongoing neurodegeneration induced by neuroinflammation. In this study, we investigated whether the PET tracer (18)F FEAnGA was able to detect beta-glucuronidase release during neuroinflammation in a rat model of herpes encephalitis. METHODS: Male Wistar rats were intranasally inoculated with herpes simplex virus 1 (HSV-1) or phosphate-buffered saline as a control. (11)C-(R)-PK11195 and (18)F-FEAnGA small-animal PET scans were acquired for 60 min. Logan graphical analysis was used to calculate (18)F-FEAnGA distribution volumes (DV(Logan)) in various brain areas. RESULTS: After administration of (18)F-FEAnGA, the area under the activity concentration-versus time curve of the whole brain was 2 times higher in HSV-1-infected rats than in control rats. In addition, the DV(Logan) of (18)F-FEAnGA was most increased in the frontopolar cortex, frontal cortex, bulbus olfactorius, cerebral cortex, cerebellum, and brainstem of HSV-1-infected rats, when compared with control rats. The conversion of (18)F-FEAnGA to 4-hydroxy-3-nitrobenzyl alcohol was found to be 1.6 times higher in HSV-1-infected rats than in control rats and correlated with the DV(Logan) of (18)F-FEAnGA in the same areas of the brain. Furthermore, the DV(Logan) of (18)F-FEAnGA also correlated with beta-glucuronidase activity in the same brain regions. In addition, DV(Logan) of (18)F-FEAnGA showed a tendency to correlate with (11)C-(R)-PK11195 uptake (marker for activated microglia) in the same brain regions. CONCLUSION: Despite relatively low brain uptake, (18)F FEAnGA was able to detect an increased release of beta-glucuronidase during neuroinflammation. PMID- 22323775 TI - Utility of diagnostic whole-body iodine scanning in high-risk differentiated thyroid carcinoma. PMID- 22323776 TI - Strigolactones suppress adventitious rooting in Arabidopsis and pea. AB - Adventitious root formation is essential for the propagation of many commercially important plant species and involves the formation of roots from nonroot tissues such as stems or leaves. Here, we demonstrate that the plant hormone strigolactone suppresses adventitious root formation in Arabidopsis (Arabidopsis thaliana) and pea (Pisum sativum). Strigolactone-deficient and response mutants of both species have enhanced adventitious rooting. CYCLIN B1 expression, an early marker for the initiation of adventitious root primordia in Arabidopsis, is enhanced in more axillary growth2 (max2), a strigolactone response mutant, suggesting that strigolactones restrain the number of adventitious roots by inhibiting the very first formative divisions of the founder cells. Strigolactones and cytokinins appear to act independently to suppress adventitious rooting, as cytokinin mutants are strigolactone responsive and strigolactone mutants are cytokinin responsive. In contrast, the interaction between the strigolactone and auxin signaling pathways in regulating adventitious rooting appears to be more complex. Strigolactone can at least partially revert the stimulatory effect of auxin on adventitious rooting, and auxin can further increase the number of adventitious roots in max mutants. We present a model depicting the interaction of strigolactones, cytokinins, and auxin in regulating adventitious root formation. PMID- 22323777 TI - 99mTc-labeled superparamagnetic iron oxide nanoparticles for multimodality SPECT/MRI of sentinel lymph nodes. AB - The purpose of this study was to develop multimodality SPECT/MRI contrast agents for sentinel lymph node (SLN) mapping in vivo. METHODS: Nanoparticles with a solid iron oxide core and a polyethylene glycol coating were labeled with (99m)Tc. The labeling efficiency was determined with instant thin-layer chromatography and magnetic separation. The stability of the radiolabeled superparamagnetic iron oxide nanoparticles (SPIONs) was verified in both sterile water and human serum at room temperature 6 and 24 h after labeling. Five Wistar rats were injected subcutaneously in the right hind paw with (99m)Tc-SPIONs (25 50 MBq, ~0.2 mg of Fe) and sacrificed 4 h after injection. Two animals were imaged with SPECT/MRI. All 5 rats were dissected; the lymph nodes, liver, kidneys, spleen, and hind paw containing the injection site were removed and weighed; and activity in the samples was measured. The microdistribution within the lymph nodes was studied with digital autoradiography. RESULTS: The efficiency of labeling of the SPIONs was 99% 6 h after labeling in both water and human serum. The labeling yield was 98% in water and 97% in human serum 24 h after labeling. The SLN could be identified in vivo with SPECT/MRI. The accumulation of (99m)Tc-SPIONs (as the percentage injected dose/g [%ID/g]) in the SLN was 100 %ID/g, whereas in the liver and spleen it was less than 2 %ID/g. Digital autoradiography images revealed a nonhomogeneous distribution of (99m)Tc-SPIONs within the lymph nodes; nanoparticles were found in the cortical, subcapsular, and medullary sinuses. CONCLUSION: This study revealed the feasibility of labeling SPIONs with (99m)Tc. The accumulation of (99m)Tc-SPIONs in lymph nodes after subcutaneous injection in animals, verified by SPECT/MRI, is encouraging for applications in breast cancer and malignant melanoma. PMID- 22323778 TI - Looking for myocardial viability after a STICH trial: not enough to close the door. PMID- 22323779 TI - Subregional patterns of preferential striatal dopamine transporter loss differ in Parkinson disease, progressive supranuclear palsy, and multiple-system atrophy. AB - Parkinson disease (PD), progressive supranuclear palsy (PSP), and multiple-system atrophy (MSA) are known to affect dopaminergic neurons of the brain stem and striatum with different preferential involvement. Here we investigated differences in striatal subregional dopamine transporter loss in PD, PSP, and MSA and assessed the diagnostic value of (18)F-fluorinated-N-3-fluoropropyl-2-beta carboxymethoxy-3-beta-(4-iodophenyl)nortropane ((18)F-FP-CIT) PET in differentiating PSP and MSA from PD. METHODS: Forty-nine patients with PD, 19 patients with PSP, 24 patients with MSA, and 21 healthy people (healthy controls) were examined with (18)F-FP-CIT PET. The PET images were spatially normalized and analyzed with 12 striatal subregional volume-of-interest (VOI) templates (bilateral ventral striatum [VS], anterior caudate [AC], posterior caudate, anterior putamen, posterior putamen [PP], and ventral putamen [VP]) and 1 occipital VOI template. The nondisplaceable binding potential (BP(ND)) and intersubregional ratio (ISR; defined as the ratio of the BP(ND) of one striatal subregion to that of another striatal subregion) of subregional VOIs were calculated. RESULTS: The BP(ND) of all VOIs in the PD, MSA, and PSP groups were significantly lower than those in the healthy controls (P < 0.05). The BP(ND) of AC and the AC/VS ISR in the PSP group were significantly lower than those in the PD group. The BP(ND) of VP was significantly lower, but the PP/VP ISR was significantly higher in the MSA group than in the PD group. At the cutoff value for the AC/VS ISR (<0.7), the sensitivity and specificity for differentiating PSP from PD were 94% and 92%, respectively. At the cutoff value for the PP/VP ISR (>0.65), the sensitivity and specificity for differentiating MSA from PD were 90% and 45%, respectively. The diagnostic accuracy of visual analysis was similar to that of quantitative analysis for differentiating PSP from PD but was significantly higher for differentiating MSA from PD. CONCLUSION: Compared with PD, PSP and MSA showed more prominent and earlier dopamine transporter loss in the AC and VP, respectively. These findings could be useful for suggesting PSP or MSA in parkinsonian cases without characteristic atypical features. PMID- 22323780 TI - Impact of 3,4-dihydroxy-6-18F-fluoro-L-phenylalanine PET/CT on managing patients with brain tumors: the referring physician's perspective. AB - We investigated the impact of (18)F-DOPA brain PET/CT on the clinical management of patients with known or suspected brain tumors. METHODS: A prospective survey of referring physicians was conducted. A pre-PET questionnaire inquired about indication, tumor histology or grade, level of suspicion for tumor recurrence, and planned management. Early post-PET questionnaires asked referring physicians to categorize PET findings as negative, equivocal, or positive; assessed the level of suspicion for primary or recurrent brain tumor; and recorded intended management changes prompted by PET findings. A late follow-up questionnaire 6 mo after the scan aimed at determining patient outcome (recurrence, survival). In addition, all referring physicians were contacted to determine whether management changes intended after (18)F-DOPA PET/CT were implemented. RESULTS: Fifty-eight consecutive patients were included. The clinical suspicion for recurrence increased in 33%, remained unchanged in 50%, and decreased in 17% of patients after adding the PET/CT result to the available diagnostic data. The late post PET questionnaire confirmed recurrence in 26 patients whereas 32 had stable disease or remained disease-free. (18)F-DOPA PET/CT resulted in intended management changes in 41% of patients. Changes in intended management from wait and watch to chemotherapy (6 patients [25%]) and from chemotherapy to wait and watch (4 patients [17%]) occurred most frequently. Clinical follow-up revealed that 75% of intended treatment changes were implemented. CONCLUSION: (18)F-DOPA PET/CT changed the intended management of 41% of patients with brain tumors, and intended management changes were implemented in 75% of these. These changes suggest a potentially important clinical role of imaging amino acid transport in the management of brain tumor patients. PMID- 22323781 TI - Bringing physiology into PET of the liver. AB - Several physiologic features make interpretation of PET studies of liver physiology an exciting challenge. As with other organs, hepatic tracer kinetics using PET is quantified by dynamic recording of the liver after the administration of a radioactive tracer, with measurements of time-activity curves in the blood supply. However, the liver receives blood from both the portal vein and the hepatic artery, with the peak of the portal vein time-activity curve being delayed and dispersed compared with that of the hepatic artery. The use of a flow-weighted dual-input time-activity curve is of importance for the estimation of hepatic blood perfusion through initial dynamic PET recording. The portal vein is inaccessible in humans, and methods of estimating the dual-input time-activity curve without portal vein measurements are being developed. Such methods are used to estimate regional hepatic blood perfusion, for example, by means of the initial part of a dynamic (18)F-FDG PET/CT recording. Later, steady state hepatic metabolism can be assessed using only the arterial input, provided that neither the tracer nor its metabolites are irreversibly trapped in the prehepatic splanchnic area within the acquisition period. This is used in studies of regulation of hepatic metabolism of, for example, (18)F-FDG and (11)C palmitate. PMID- 22323782 TI - Clinical validation of 18F-AZD4694, an amyloid-beta-specific PET radioligand. AB - Pioneered with the invention of (11)C-Pittsburgh compound B, amyloid-beta imaging using PET has facilitated research in Alzheimer disease (AD). This imaging approach has promise for diagnostic purposes and evaluation of disease-modifying therapies. Broad clinical use requires an (18)F-labeled amyloid-beta radioligand with high specific and low nonspecific binding. The aim of the present PET study was to examine the radioligand (18)F-AZD4694 in human subjects. METHODS: Six control subjects and 10 clinically diagnosed AD patients underwent PET examination with (18)F-AZD4694 and a structural MRI scan. Of these, 4 controls and 4 patients underwent a second PET examination for test-retest analysis. Arterial sampling was done to derive a metabolite-corrected plasma input function for traditional compartment modeling. Besides, several simplified quantitative approaches were applied, including the reference Logan approach and simple ratio methods. RESULTS: After intravenous injection of (18)F-AZD4694, radioactivity appeared rapidly in brain. In patients, radioactivity was high in regions expected to contain amyloid-beta, whereas in controls, radioactivity was low and homogenously distributed. Binding in cerebellum, a reference region, was low and similar between the groups. Specific binding was reversible and peaked at about 27 min after injection in regions with high radioactivity. The time-activity curves could be described using the 2-tissue-compartment model. Distribution volume ratio estimates obtained using compartment models and simplified methods were highly correlated. Standardized uptake value ratios calculated at late times and distribution volume ratios estimated with the reference Logan approach were, in gray matter, significantly lower in control subjects (1.08 [11%] and 1.01 [6%], respectively) than in AD patients (2.15 [24%] and 1.62 [18%], respectively). Among noninvasive methods, the lowest test-retest variability was found with reference Logan, varying between 4% and 6% across brain regions. CONCLUSION: Noninvasive quantitative approaches provide valid estimates of amyloid-beta binding. Because of the radioisotope ((18)F) used for labeling, the radioligand has potential for wide clinical application. (18)F-AZD4694 satisfies the requirements for a promising amyloid-beta radioligand both for diagnostic use and for evaluation of disease-modifying therapies in AD. PMID- 22323783 TI - Transport of indole-3-butyric acid and indole-3-acetic acid in Arabidopsis hypocotyls using stable isotope labeling. AB - The polar transport of the natural auxins indole-3-butyric acid (IBA) and indole 3-acetic acid (IAA) has been described in Arabidopsis (Arabidopsis thaliana) hypocotyls using radioactive tracers. Because radioactive assays alone cannot distinguish IBA from its metabolites, the detected transport from applied [3H]IBA may have resulted from the transport of IBA metabolites, including IAA. To test this hypothesis, we used a mass spectrometry-based method to quantify the transport of IBA in Arabidopsis hypocotyls by following the movement of [13C1]IBA and the [13C1]IAA derived from [13C1]IBA. We also assayed [13C6]IAA transport in a parallel control experiment. We found that the amount of transported [13C1]IBA was dramatically lower than [13C6]IAA, and the IBA transport was not reduced by the auxin transport inhibitor N-1-naphthylphthalamic acid. Significant amounts of the applied [13C1]IBA were converted to [13C1]IAA during transport, but [13C1]IBA transport was independent of IBA-to-IAA conversion. We also found that most of the [13C1]IBA was converted to ester-linked [13C1]IBA at the apical end of hypocotyls, and ester-linked [13C1]IBA was also found in the basal end at a level higher than free [13C1]IBA. In contrast, most of the [13C6]IAA was converted to amide-linked [13C6]IAA at the apical end of hypocotyls, but very little conjugated [13C6]IAA was found in the basal end. Our results demonstrate that the polar transport of IBA is much lower than IAA in Arabidopsis hypocotyls, and the transport mechanism is distinct from IAA transport. These experiments also establish a method for quantifying the movement of small molecules in plants using stable isotope labeling. PMID- 22323785 TI - The endangered bond. PMID- 22323784 TI - Lightness perception in high dynamic range images: local and remote luminance effects. AB - We measured the perceived lightness of target patches embedded in high dynamic range checkerboards. We independently varied the luminance of checks immediately surrounding the test and those remote from it. The data establish context transfer functions (CTFs) that characterize perceptual matches across checkerboard contexts. Several features of the CTFs are broadly consistent with previous research: Matched luminance decreases when overall context luminance decreases; matched luminance increases when overall context luminance increases; manipulating context locations near the target has a greater effect than manipulating locations far from the target patch. The measured CTFs are not well described, however, by changes with context in multiplicative gain alone or by changes in both multiplicative and subtractive adaptation parameters. We were able to fit the data with a three-parameter model of adaptation. This allowed us to characterize the CTFs by specifying the luminances that appeared white, black, and gray (white point, black point, and gray point, respectively). The white and black points depended additively on the local and remote contrasts, but accounting for the gray point required an interaction term. Analysis of this effect suggests that the target patch itself must be included in a description of the visual context. PMID- 22323789 TI - France. ?22 billion stimulus brings worries about egalite. PMID- 22323790 TI - Personalized medicine. New cystic fibrosis drug offers hope, at a price. PMID- 22323791 TI - Paleontology. More than one way for invaders to wreak havoc. PMID- 22323792 TI - Eastern Europe. High hopes for Croatia's 'Warm Spring Harbor' remain unfulfilled. PMID- 22323793 TI - Indoor ecosystems. PMID- 22323794 TI - Profile: Stephen Friend. The visionary. PMID- 22323795 TI - Carbon shifted but not sequestered. PMID- 22323797 TI - Ecosystem services: heed social goals. PMID- 22323798 TI - Ecosystem services: free lunch no more. PMID- 22323802 TI - Comment on "Phonemic diversity supports a serial founder effect model of language expansion from Africa". AB - We show that Atkinson's (Reports, 15 April 2011, p. 346) intriguing proposal- that global linguistic diversity supports a single language origin in Africa--is an artifact of using suboptimal data, biased methodology, and unjustified assumptions. We criticize his approach using more suitable data, and we additionally provide new results suggesting a more complex scenario for the emergence of global linguistic diversity. PMID- 22323803 TI - Comment on "Phonemic diversity supports a serial founder effect model of language expansion from Africa". AB - Atkinson (Reports, 15 April 2011, p. 346) reported a declined trend of phonemic diversity from Africa that indicated the African exodus of modern languages. However, his claim was only supported when the phonemic diversities were binned into three or five levels. Analyses using raw data without simplification suggest a decline from central Asia rather than from Africa. PMID- 22323804 TI - Comment on "Phonemic diversity supports a serial founder effect model of language expansion from Africa". AB - Atkinson (Reports, 15 April 2011, p. 346) concluded that language originated in western Africa and that, due to a serial founder effect, languages repeatedly lost phonemes the farther they moved from the African point of origin. Independent examination of the published data tends to refute both these claims. PMID- 22323806 TI - Neuroscience. Ode to the mushroom bodies. PMID- 22323807 TI - Mathematics. Critical truths about power laws. PMID- 22323808 TI - Immunology. Remembering to be tolerant. PMID- 22323809 TI - Chemistry. Probing frozen molecular embraces. PMID- 22323810 TI - Structural biology. It's all in the symmetry. PMID- 22323811 TI - Seasonality in ocean microbial communities. AB - Ocean warming occurs every year in seasonal cycles that can help us to understand long-term responses of plankton to climate change. Rhythmic seasonal patterns of microbial community turnover are revealed when high-resolution measurements of microbial plankton diversity are applied to samples collected in lengthy time series. Seasonal cycles in microbial plankton are complex, but the expansion of fixed ocean stations monitoring long-term change and the development of automated instrumentation are providing the time-series data needed to understand how these cycles vary across broad geographical scales. By accumulating data and using predictive modeling, we gain insights into changes that will occur as the ocean surface continues to warm and as the extent and duration of ocean stratification increase. These developments will enable marine scientists to predict changes in geochemical cycles mediated by microbial communities and to gauge their broader impacts. PMID- 22323812 TI - Pigment pattern formation by contact-dependent depolarization. AB - Although recent experimental studies have suggested that the interactions among the pigment cells play a key role in the skin pattern formation, details of the mechanism remain largely unknown. By using an in vitro cell culture system, we have detected interactions between the two pigment cell types, melanophores and xanthophores, in the zebrafish skin. During primary culture, the melanophore membrane transiently depolarizes when contacted with the dendrites of a xanthophore. This depolarization triggers melanophore migration to avoid further contact with the xanthophores. Cell depolarization and repulsive movement were not observed in pigment cells with the jaguar mutant, which shows defective segregation of melanophores and xanthophores. The depolarization-repulsion of wild-type pigment cells may explain the pigment cell behaviors generating the stripe pattern of zebrafish. PMID- 22323813 TI - Visualizing long-term memory formation in two neurons of the Drosophila brain. AB - Long-term memory (LTM) depends on the synthesis of new proteins. Using a temperature-sensitive ribosome-inactivating toxin to acutely inhibit protein synthesis, we screened individual neurons making new proteins after olfactory associative conditioning in Drosophila. Surprisingly, LTM was impaired after inhibiting protein synthesis in two dorsal-anterior-lateral (DAL) neurons but not in the mushroom body (MB), which is considered the adult learning and memory center. Using a photoconvertible fluorescent protein KAEDE to report de novo protein synthesis, we have directly visualized cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB)-dependent transcriptional activation of calcium/calmodulin-dependent protein kinase II and period genes in the DAL neurons after spaced but not massed training. Memory retention was impaired by blocking neural output in DAL during retrieval but not during acquisition or consolidation. These findings suggest an extra-MB memory circuit in Drosophila: LTM consolidation (MB to DAL), storage (DAL), and retrieval (DAL to MB). PMID- 22323814 TI - Structural insight into the ion-exchange mechanism of the sodium/calcium exchanger. AB - Sodium/calcium (Na(+)/Ca(2+)) exchangers (NCX) are membrane transporters that play an essential role in maintaining the homeostasis of cytosolic Ca(2+) for cell signaling. We demonstrated the Na(+)/Ca(2+)-exchange function of an NCX from Methanococcus jannaschii (NCX_Mj) and report its 1.9 angstrom crystal structure in an outward-facing conformation. Containing 10 transmembrane helices, the two halves of NCX_Mj share a similar structure with opposite orientation. Four ion binding sites cluster at the center of the protein: one specific for Ca(2+) and three that likely bind Na(+). Two passageways allow for Na(+) and Ca(2+) access to the central ion-binding sites from the extracellular side. Based on the symmetry of NCX_Mj and its ability to catalyze bidirectional ion-exchange reactions, we propose a structure model for the inward-facing NCX_Mj. PMID- 22323815 TI - One-step fabrication of supramolecular microcapsules from microfluidic droplets. AB - Although many techniques exist for preparing microcapsules, it is still challenging to fabricate them in an efficient and scalable process without compromising functionality and encapsulation efficiency. We demonstrated a simple one-step approach that exploits a versatile host-guest system and uses microfluidic droplets to generate porous microcapsules with easily customizable functionality. The capsules comprise a polymer-gold nanoparticle composite held together by cucurbit[8]uril ternary complexes. The dynamic yet highly stable micrometer-sized structures can be loaded in one step during capsule formation and are amenable to on-demand encapsulant release. The internal chemical environment can be probed with surface enhanced Raman spectroscopy. PMID- 22323816 TI - A molecular MoS2 edge site mimic for catalytic hydrogen generation. AB - Inorganic solids are an important class of catalysts that often derive their activity from sparse active sites that are structurally distinct from the inactive bulk. Rationally optimizing activity is therefore beholden to the challenges in studying these active sites in molecular detail. Here, we report a molecule that mimics the structure of the proposed triangular active edge site fragments of molybdenum disulfide (MoS(2)), a widely used industrial catalyst that has shown promise as a low-cost alternative to platinum for electrocatalytic hydrogen production. By leveraging the robust coordination environment of a pentapyridyl ligand, we synthesized and structurally characterized a well-defined Mo(IV)-disulfide complex that, upon electrochemical reduction, can catalytically generate hydrogen from acidic organic media as well as from acidic water. PMID- 22323817 TI - Near-field deformation from the El Mayor-Cucapah earthquake revealed by differential LIDAR. AB - Large [moment magnitude (M(w)) >= 7] continental earthquakes often generate complex, multifault ruptures linked by enigmatic zones of distributed deformation. Here, we report the collection and results of a high-resolution (>=nine returns per square meter) airborne light detection and ranging (LIDAR) topographic survey of the 2010 M(w) 7.2 El Mayor-Cucapah earthquake that produced a 120-kilometer-long multifault rupture through northernmost Baja California, Mexico. This differential LIDAR survey completely captures an earthquake surface rupture in a sparsely vegetated region with pre-earthquake lower-resolution (5 meter-pixel) LIDAR data. The postevent survey reveals numerous surface ruptures, including previously undocumented blind faults within thick sediments of the Colorado River delta. Differential elevation changes show distributed, kilometer scale bending strains as large as ~10(3) microstrains in response to slip along discontinuous faults cutting crystalline bedrock of the Sierra Cucapah. PMID- 22323818 TI - Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation. AB - DNMT1, the major maintenance DNA methyltransferase in animals, helps to regulate gene expression, genome imprinting, and X-chromosome inactivation. We report on the crystal structure of a productive covalent mouse DNMT1(731-1602)-DNA complex containing a central hemimethylated CpG site. The methyl group of methylcytosine is positioned within a shallow hydrophobic concave surface, whereas the cytosine on the target strand is looped out and covalently anchored within the catalytic pocket. The DNA is distorted at the hemimethylated CpG step, with side chains from catalytic and recognition loops inserting through both grooves to fill an intercalation-type cavity associated with a dual base flip-out on partner strands. Structural and biochemical data establish how a combination of active and autoinhibitory mechanisms ensures the high fidelity of DNMT1-mediated maintenance DNA methylation. PMID- 22323819 TI - Structure and allostery of the PKA RIIbeta tetrameric holoenzyme. AB - In its physiological state, cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) is a tetramer that contains a regulatory (R) subunit dimer and two catalytic (C) subunits. We describe here the 2.3 angstrom structure of full-length tetrameric RIIbeta(2):C(2) holoenzyme. This structure showing a dimer of dimers provides a mechanistic understanding of allosteric activation by cAMP. The heterodimers are anchored together by an interface created by the beta4-beta5 loop in the RIIbeta subunit, which docks onto the carboxyl-terminal tail of the adjacent C subunit, thereby forcing the C subunit into a fully closed conformation in the absence of nucleotide. Diffusion of magnesium adenosine triphosphate (ATP) into these crystals trapped not ATP, but the reaction products, adenosine diphosphate and the phosphorylated RIIbeta subunit. This complex has implications for the dissociation-reassociation cycling of PKA. The quaternary structure of the RIIbeta tetramer differs appreciably from our model of the RIalpha tetramer, confirming the small-angle x-ray scattering prediction that the structures of each PKA tetramer are different. PMID- 22323820 TI - Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. AB - Short-term starvation (or fasting) protects normal cells, mice, and potentially humans from the harmful side effects of a variety of chemotherapy drugs. Here, we show that treatment with starvation conditions sensitized yeast cells (Saccharomyces cerevisiae) expressing the oncogene-like RAS2(val19) to oxidative stress and 15 of 17 mammalian cancer cell lines to chemotherapeutic agents. Cycles of starvation were as effective as chemotherapeutic agents in delaying progression of different tumors and increased the effectiveness of these drugs against melanoma, glioma, and breast cancer cells. In mouse models of neuroblastoma, fasting cycles plus chemotherapy drugs--but not either treatment alone--resulted in long-term cancer-free survival. In 4T1 breast cancer cells, short-term starvation resulted in increased phosphorylation of the stress sensitizing Akt and S6 kinases, increased oxidative stress, caspase-3 cleavage, DNA damage, and apoptosis. These studies suggest that multiple cycles of fasting promote differential stress sensitization in a wide range of tumors and could potentially replace or augment the efficacy of certain chemotherapy drugs in the treatment of various cancers. PMID- 22323821 TI - Saccadic eye movements in the dark while performing an automatized sequential high-speed sensorimotor task. AB - Saccades during object-related everyday tasks select visual information to guide hand movements. Nevertheless, humans can perform such a task in the dark provided it was automatized beforehand. It is largely unknown whether and how saccades are executed in this case. Recently, a long-term memory (LTM)-based direct control mode of attention during the execution of well-learned sensorimotor tasks, which predicts task-relevant saccades in the dark, was proposed (R. M. Foerster, E. Carbone, H. Koesling, & W. X. Schneider, 2011). In the present study, participants performed an automatized speed-stacking task in the dark and in the light while their eye movements were recorded. Speed stacking is a sequential high-speed sensorimotor object manipulation task. Results demonstrated that participants indeed made systematic eye movements in the dark. Saccadic scan paths and the number of fixations were highly similar across illumination conditions, while fixation rates were lower and fixation durations were longer in the dark. Importantly, the eye reached a location ahead of the hands even in the dark. Finally, neither eye-hand dynamics nor saccade accuracy correlated with hand movement durations in the dark. Results support the hypothesis of an LTM based mode of attention selection during the execution of automatized sequential high-speed sensorimotor tasks. PMID- 22323822 TI - Head and eye gaze dynamics during visual attention shifts in complex environments. AB - The dynamics of overt visual attention shifts evoke certain patterns of responses in eye and head movements. In this work, we detail novel findings regarding the interaction of eye gaze and head pose under various attention-switching conditions in complex environments and safety critical tasks such as driving. In particular, we find that sudden, bottom-up visual cues in the periphery evoke a different pattern of eye-head movement latencies as opposed to those during top down, task-oriented attention shifts. In laboratory vehicle simulator experiments, a unique and significant (p < 0.05) pattern of preparatory head motions, prior to the gaze saccade, emerges in the top-down case. This finding is validated in qualitative analysis of naturalistic real-world driving data. These results demonstrate that measurements of eye-head dynamics are useful data for detecting driver distractions, as well as in classifying human attentive states in time and safety critical tasks. PMID- 22323823 TI - Brain distribution of cediranib is limited by active efflux at the blood-brain barrier. AB - Cediranib is an orally active tyrosine kinase inhibitor that targets the vascular endothelial growth factor receptor family. Because of its potent antiangiogenic and antitumor activities, cediranib has been evaluated for therapy in glioma, a primary brain tumor. This study investigated the influence of two important efflux transporters at the blood-brain barrier, P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp), on the delivery of cediranib to the central nervous system. In vitro studies indicated that cediranib is a dual substrate for both P-gp and Bcrp. It is noteworthy that in spite of the in vitro data the in vivo mouse disposition studies conclusively showed that P-gp was the dominant transporter restricting the brain distribution of cediranib. The brain-to-plasma partitioning (AUC(brain)/AUC(plasma), where AUC is area under the curve) and the steady-state brain-to-plasma concentration ratio of cediranib were approximately 20-fold higher in Mdr1a/b-/- and Mdr1a/b-/-Bcrp1-/- mice compared with wild-type and Bcrp1-/- mice. Moreover, there was no significant difference in brain distribution of cediranib between wild-type and Bcrp1-/- mice and between Mdr1a/b /- and Mdr1a/b-/-Bcrp1-/- mice. These results show that, unlike other tyrosine kinase inhibitors that are dual substrates for P-gp and Bcrp, Bcrp does not restrict the distribution of cediranib across the blood-brain barrier. We also show that inhibition of P-gp using specific or nonspecific inhibitors resulted in significantly enhanced delivery of cediranib to the brain. Concurrent administration of cediranib with chemical modulators of efflux transporters can be used as a strategy to enhance delivery and thus efficacy of cediranib in the brain. These findings are clinically relevant to the efficacy of cediranib chemotherapy in glioma. PMID- 22323824 TI - Activation of adenosine1 receptors induces antidepressant-like, anti-impulsive effects on differential reinforcement of low-rate 72-s behavior in rats. AB - Stress and psychiatric illness have been associated with a dysregulation of glutamatergic neurotransmission. Recently, positive allosteric modulators (PAMs) of the metabotropic glutamate 2 (mGlu2) receptor have been found to exert antidepressant-like activity in rats performing under a differential reinforcement of low rate (DRL) 72-s schedule. An autoreceptor role at glutamatergic synapses is the most salient physiological role played by the mGlu2 receptor. Adenosine A1 receptors play a heteroreceptor role at many of the same forebrain synapses where mGlu2 autoreceptors are found. Agonists and/or PAMs of mGlu2 receptors act similarly to adenosine A1 receptor agonists with respect to a wide range of electrophysiological, biochemical, and behavioral responses mediated by limbic circuitry thought to play a role in the pathophysiology of neuropsychiatric disease and to mediate therapeutic drug effects. Therefore, the role of adenosine A1 receptor activation on rat DRL 72-s behavior was explored to provide preclinical evidence consistent or inconsistent with potential antidepressant effects. The adenosine A1 receptor agonist N6-cyclohexyladenosine (CHA) increased the reinforcement rate, decreased the response rate, and induced a rightward shift in inter-response time distributions in a dose-dependent fashion similar to most known antidepressant drugs. The adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) blocked these antidepressant-like effects. These novel observations with CHA and DPCPX suggest that activation of adenosine A1 receptors could contribute to antidepressant effects, in addition to previous preclinical reports of anxiolytic and antipsychotic effects. By implication, targeting a dysregulated glutamatergic system may be an important principle in discovering novel antidepressant agents that may also possess anti-impulsive activity. PMID- 22323826 TI - Improving immunotherapy: revisiting the immunologist's little secret. AB - Synergy between intracellular and extracellular sensing mechanisms of the innate immune system improves adaptive immune responses to cancer vaccines and clearance of tumors. PMID- 22323825 TI - Cross-talk between receptor tyrosine kinase and tumor necrosis factor-alpha signaling networks regulates apoptosis but not proliferation. AB - Although many of the signaling networks activated by receptor tyrosine kinases (RTKs) and cytokine receptors are well understood, how these networks interconnect is much less clear. We set out to determine how cells respond to simultaneous exposure to opposing signals and how their downstream networks process this information. Using six isogenic cell lines, each stably transfected with a different RTK, we found that, in each case, the cognate growth factor induced proliferation, whereas TNFalpha induced apoptosis. Surprisingly, when the cells were treated simultaneously with growth factor and TNFalpha, the growth factor enhanced, rather than antagonized, TNFalpha-induced cell death. In contrast, TNFalpha had no effect on growth factor-induced proliferation, suggesting that cross-talk between these networks is unidirectional. A quantitative, system-wide study of signaling at early and late time points corroborated this observation: proteins in the RTK networks were not affected by TNFalpha treatment, but proteins in the TNFalpha network were affected by growth factors. These studies also highlighted the stress mitogen-activated protein kinase proteins p38 and c-Jun N-terminal kinase as the key nodes of signal integration, and their activation states at an early time point correlated well with subsequent measurements of apoptosis. Knocking down cRaf reduced the growth factor enhancement of TNFalpha-induced apoptosis, highlighting its role as a regulator of network cross-talk upstream of p38 and c-Jun N-terminal kinase. Overall, we found that when cells encounter conflicting stimuli, their phenotypic response is determined not by the sum of isolated processes, but by how their signaling networks interconnect. This underscores the need to build mechanistic models of network integration as a first step in predicting cellular behavior in complex settings and in rationally designing combination therapies. PMID- 22323827 TI - Escaping ALK inhibition: mechanisms of and strategies to overcome resistance. AB - Mutated anaplastic lymphoma kinase (ALK) drives the development of multiple tumor types, and ALK tyrosine kinase inhibitors such as crizotinib have been validated as targeted therapeutics. Unfortunately, as with other oncogene-driven tumors, therapeutic resistance invariably develops. In Science Translational Medicine, two recent studies provide new insight into mechanisms of resistance to ALK tyrosine kinase inhibitors and possible strategies to overcome this resistance. PMID- 22323828 TI - AAV2 gene therapy readministration in three adults with congenital blindness. AB - Demonstration of safe and stable reversal of blindness after a single unilateral subretinal injection of a recombinant adeno-associated virus (AAV) carrying the RPE65 gene (AAV2-hRPE65v2) prompted us to determine whether it was possible to obtain additional benefit through a second administration of the AAV vector to the contralateral eye. Readministration of vector to the second eye was carried out in three adults with Leber congenital amaurosis due to mutations in the RPE65 gene 1.7 to 3.3 years after they had received their initial subretinal injection of AAV2-hRPE65v2. Results (through 6 months) including evaluations of immune response, retinal and visual function testing, and functional magnetic resonance imaging indicate that readministration is both safe and efficacious after previous exposure to AAV2-hRPE65v2. PMID- 22323829 TI - Simultaneous targeting of toll- and nod-like receptors induces effective tumor specific immune responses. AB - Toll-like receptor (TLR) ligands are increasingly being used as adjuvants in cancer vaccine trials to harness innate immunity and prime effective antitumor immune responses. Despite some success, enhancing tumor antigen presentation, promoting a protective antitumor response, and overcoming the immunosuppressive tumor microenvironment pose considerable challenges that necessitate further improvements in vaccine design. Here, we show that expression of the TLR ligand flagellin within tumor cells constitutes an effective antitumor vaccination strategy that relies on simultaneous engagement of TLR5 and the Nod-like receptors (NLRs) NLRC4/NAIP5 (neuronal apoptosis inhibitory protein 5) by flagellin along with associative recognition of tumor antigen for optimal antigen presentation to T cells. Although TLR5 signaling was critical for mediating rapid macrophage-dependent clearance of flagellin-expressing tumor cells in vivo, TLR5 and NLRC4/NAIP5 were equally important for priming antitumor CD4(+) and CD8(+) T cells and suppressing tumor growth. Vaccination with irradiated flagellin expressing tumor cells prevented tumor development, and disrupting flagellin recognition by TLR5 or NLRC4/NAIP5 impaired protective immunization against an existing or subsequent tumor. Our findings delineate a new strategy to induce anticancer immune responses consisting of introducing microbial structures with dual TLR and NLR stimulatory activity into tumor cells. This ensures recognition of tumor-derived antigen within the inflammatory context of microbial recognition and additionally activates both the phagocytic and the cytosolic pathways of innate immune defense against the tumor. PMID- 22323830 TI - Longitudinal magnetic resonance spectroscopy as marker of cognitive deterioration in mild cognitive impairment. AB - OBJECTIVE: Amnestic mild cognitive impairment (MCI) is highly predictive of Alzheimer's disease but the pace of deterioration varies across patients. We hypothesize that magnetic resonance spectroscopy (MRS) could be a useful surrogate marker to monitor progression of cognitive impairment in patients with amnestic MCI. METHODS: A cohort of patients with amnestic MCI underwent single voxel (1)H-MRS at baseline and at 2-year follow-up. We included 16 patients who converted to dementia of Alzheimer type and other 16 who did not. Changes in cognitive function were compared with the changes in the metabolite levels assessed in vivo. RESULTS: At baseline the converters had lower mean N-acetyl aspartate (NAA)/creatine (Cr) ratios in the posteromedial parietal cortex (1.41) than nonconverters (1.47). Most patients tended to lose points in the Mini-Mental test after 2-year follow-up in parallel with decreases in NAA levels (r = .53; P = .002) in the posteromedial parietal cortex as well. The converters showed significant decreases in NAA levels and Cr ratios, whereas the nonconverters did not (P = .001 and .02, respectively) in this area. CONCLUSION: We conclude that MRS is a technique sensitive enough to monitor cognitive changes and progression to dementia in patients with amnestic MCI. PMID- 22323831 TI - Use of dietary supplements for cognitive health: results of a national survey of adults in the United States. AB - We studied use of vitamins, minerals, herbs, and other dietary supplements for cognitive health. We refer to these products as supplements. Data were from the 2007 National Health Interview Survey, which asked about complementary and alternative medicine (n = 22 783). Chi-square and multivariate logistic analyses were weighted for national representativeness, accounting for the survey design. Among supplement users, about 8.8% of those without cognitive problems used them for cognitive health; 15.7% of those with cognitive problems did so. Fish oil, Ginkgo biloba, and vitamins were commonly used for cognitive health. Among supplement users, 38% did not tell health care providers. In adjusted results, adults reporting cognitive problems were more likely than others to use supplements for cognitive health (odds ratio 1.77, confidence interval 1.39 2.25). Adults are more likely to use supplements to treat or cure cognitive problems than to prevent them. Many do not discuss this use with health care providers. PMID- 22323832 TI - Radial artery sterile granulomatous reaction secondary to hydrophilic-coated sheath used for transradial cardiac catheterization: a case series. AB - Radial access has lower risk of vascular complication for cardiac catheterization and is rapidly replacing femoral access. There are few unique complications associated with this approach. We present 3 cases of sterile granulomatous reaction associated with a specific hydrophilic radial sheath and possibly contribution by radial wrist band [TR band; Terumo Medical used for hemostasis after sheath removal (2101 cotton tail lane somerset NJ, USA)]. Awareness of this association will help clinicians use appropriate preventive measures. PMID- 22323833 TI - Clinical usefulness of assessment of ankle-brachial index and carotid stenosis in type 2 diabetic population--three-year cohort follow-up of mortality. AB - We evaluated the clinical usefulness of assessing the ankle-brachial index (ABI) and carotid stenosis (CS) in a type 2 diabetic population. Patients with type 2 diabetes and coronary artery disease (n = 265) were enrolled in a prospective 3 year cohort study. The cardiovascular mortality rate was 8.7% (23 of 265) during the 36-month study and the all-cause mortality rate was 9.5% (25 of 265). Multivariate logistic regression analysis revealed that age (odds ratio [OR] 2.09), hypertension (OR 7.99), obesity (OR 4.86), internal CS (OR 262.17), and Gensini score (OR 1.15) were independent predictors of cardiovascular mortality. Mean ABI value (OR 0.15) was the only predictor of all-cause mortality in this population. The ABI and carotid artery ultrasound have independent prognostic value in a type 2 diabetic population. PMID- 22323834 TI - A simple booklet for patient follow-up after endovascular abdominal aortic aneurysm repair procedures. AB - Endovascular abdominal aortic aneurysm (AAA) repair (EVAR) procedures require lifelong patient surveillance for the detection of complications (eg, endoleaks or graft migration). This follow-up may be suboptimal. Between November 2010 and November 2011, a follow-up booklet was provided at hospital discharge to 42 consecutive patients undergoing EVAR for an infrarenal AAA. Each patient was given specific instructions for completion of the booklet at each follow-up examination whether this took place at our hospital or elsewhere. After a mean follow-up of 7 +/- 3 months, all patients had fully complied with the instructions. This booklet may be useful for patients who find it difficult to attend follow-up appointments. Additionally, this booklet is useful for patients who move to another town/country or in cases of emergency when patients are admitted to another hospital. PMID- 22323835 TI - Outcome of patients with regadenoson-induced ST-segment depression but normal perfusion on single-photon emission computed tomography. AB - The prognostic significance of ischemic electrocardiographic (ECG) changes during Regadenoson vasodilator stress in patients with normal single-photon emission computed tomographic myocardial perfusion imaging (SPECT-MPI) is not well described. Of 2473 patients who underwent Regadenoson vasodilator stress testing, 43 (77% women, mean age 72 +/- 10 years) patients were included in the study. During a mean follow-up of 14 +/- 7 months, cardiac death occurred in 1 patient; 5 patients underwent coronary revascularization and none had myocardial infarction. The annual rate of cardiac death and coronary revascularization was 1.9% and 9.9%, respectively. The finding of ischemic ECG changes with normal SPECT-MPI during regadenoson vasodilator stress testing is uncommon, occurs primarily in older women, and is associated with moderately higher subsequent cardiac event rate. PMID- 22323836 TI - Preoperative and therapeutic embolization of extremities of bone and soft tissue tumors. AB - Embolization of bone and soft tissue tumors has a broad range of indications, from curative treatment to palliation. The main purpose of embolization is to occlude as much of the tumor blood supply as possible. The outcome ranges from complete tumor devascularization and necrosis to degrees of ischemia and hypovascularity. Thus, the tumor will shrink, bleeding will be reduced, borders between the tumor and surrounding tissue will become clear, and resection will be easier. The purpose of this study was to correlate the effectiveness of preoperative embolization with the blood loss and transfusion requirement during surgery for bone or soft tissue tumors. PMID- 22323837 TI - Obstructive sleep apnea and cardiovascular risk: is metabolic syndrome the link? PMID- 22323838 TI - Carotid intima-media thickness and carotid plaques improves prediction of obstructive angiographic coronary artery disease in women. AB - Does carotid intima-media thickness (cIMT), a surrogate marker of cardiovascular events, have predictive incremental value over established risk factors for stable coronary artery disease (CAD)? Prospective study of 300 patients, with suspected stable CAD, admitted for an elective coronary angiography and carotid ultrasound. The CAD patients had a higher cIMT, which showed a modest predictive accuracy for CAD (area under the receiver-operating characteristic curve 0.638, 95% confidence interval 0.576-0.701, P < .001). The cIMT was an independent predictor of CAD, together with age, gender, and diabetes. C-statistic for CAD prediction by traditional risk factors was not significantly different from a model that included cIMT, carotid plaque presence, or both. However, in women, it was significantly increased by the addition of cIMT or carotid plaque presence. Although cIMT cannot be used as a sole indicator of CAD, it should be considered in the panel of investigations that is requested, particularly in women who are candidates for coronary angiography. PMID- 22323839 TI - Level-Set Minimization of Potential Controlled Hadwiger Valuations for Molecular Solvation. AB - A level-set method is developed for the numerical minimization of a class of Had wiger valuations with a potential on a set of three-dimensional bodies. Such valuations are linear combinations of the volume, surface area, and surface integral of mean curvature. The potential increases rapidly as the body shrinks beyond a critical size. The combination of the Hadwiger valuation and the potential is the mean-field free-energy functional of the solvation of non-polar molecules in the recently developed variational implicit-solvent model. This functional of surfaces is minimized by the level-set evolution in the steepest decent of the free energy. The normal velocity of this surface evolution consists of both the mean and Gaussian curvatures, and a lower-order, "forcing" term arising from the potential. The forward Euler method is used to discretize the time derivative with a dynamic time stepping that satisfies a CFL condition. The normal velocity is decomposed into two parts. The first part consists of both the mean and Gaussian curvature terms. It is of parabolic type with parameter correction, and is discretized by central differencing. The second part has all the lower-order terms. It is of hyperbolic type, and is discretized by an upwinding scheme. New techniques of local level-set method and numerical integration are developed. Numerical tests demonstrate a second-order convergence of the method. Examples of application to the modeling of molecular solvation are presented. PMID- 22323840 TI - Maximum Likelihood Estimations and EM Algorithms with Length-biased Data. AB - Length-biased sampling has been well recognized in economics, industrial reliability, etiology applications, epidemiological, genetic and cancer screening studies. Length-biased right-censored data have a unique data structure different from traditional survival data. The nonparametric and semiparametric estimations and inference methods for traditional survival data are not directly applicable for length-biased right-censored data. We propose new expectation-maximization algorithms for estimations based on full likelihoods involving infinite dimensional parameters under three settings for length-biased data: estimating nonparametric distribution function, estimating nonparametric hazard function under an increasing failure rate constraint, and jointly estimating baseline hazards function and the covariate coefficients under the Cox proportional hazards model. Extensive empirical simulation studies show that the maximum likelihood estimators perform well with moderate sample sizes and lead to more efficient estimators compared to the estimating equation approaches. The proposed estimates are also more robust to various right-censoring mechanisms. We prove the strong consistency properties of the estimators, and establish the asymptotic normality of the semi-parametric maximum likelihood estimators under the Cox model using modern empirical processes theory. We apply the proposed methods to a prevalent cohort medical study. Supplemental materials are available online. PMID- 22323841 TI - Predicting the distribution of intensive poultry farming in Thailand. AB - Intensification of animal production can be an important factor in the emergence of infectious diseases because changes in production structure influence disease transmission patterns. In 2004 and 2005, Thailand was subject to two highly pathogenic avian influenza epidemic waves and large surveys were conducted of the poultry sector, providing detailed spatial data on various poultry types. This study analysed these data with the aim of establishing the distributions of extensive and intensive poultry farms, based on the number of birds per holder. Once poultry data were disaggregated into these two production systems, they were analysed in relation to anthropogenic factors using simultaneous autoregressive models. Intensive chicken production was clustered around the capital city of Bangkok and close to the main consumption and export centres. Intensively-raised ducks, mainly free-grazing, showed a distinct pattern with the highest densities distributed in a large area located in the floodplain of the Chao Phraya River. Accessibility to Bangkok, the percentage of irrigated areas and human population density were the most important predictors explaining the geographical distribution of intensively-raised poultry. The distribution of extensive poultry showed a higher predictability. Extensive poultry farms were distributed more homogeneously across the country and their distribution was best predicted by human population density. PMID- 22323842 TI - Beyond transitional selection: New roles for BLyS in peripheral tolerance. AB - B cell targeted therapies have enjoyed recent success in the treatment of systemic autoimmune diseases. Among these, Belimumab, which blocks the B cell survival cytokine BLyS, was recently approved for the treatment of Systemic Lupus Erythematosus. It is therefore important to consider the roles BLyS plays in B cell tolerance. Herein, we review how BLyS contributes to the negative selection of autoreactive B cell clones from the preimmune repertoire as well as its role in regulating both germinal center and extrafollicular peripheral B cell responses. We further examine the complex role of Toll-like receptors (TLRs) in humoral autoimmunity, pointing out potential crosstalk between BLyS and TLR pathways. PMID- 22323845 TI - Potential applications of human saliva as diagnostic fluid. AB - The use of human saliva as a diagnostic and prognostic fluid has until recently been somewhat disregarded. Although sample collection is non-invasive, physiological and genetic variations were largely responsible for its infrequent application in the past. Recently, several proteomic studies contributed to partial elucidation of the salivary proteome (more than 2400 protein components have been characterized), both in terms of composition, contributions to whole saliva and genetic/physiological variability. On this basis, is not too optimistic to believe that in the near future human saliva could become a relevant diagnostic fluid. In this review, the characterization by proteomic approaches of new salivary markers in oncology, head and neck carcinoma (oral cavity, oropharynx, larynx, and salivary glands), breast and gastric cancers, salivary gland function and disease, Sjogren syndrome, systemic sclerosis, dental and gingival pathology, systemic, psychiatric and neurological diseases, is described. PMID- 22323846 TI - Management and follow-up of thyroid cancer in pregnant women. AB - Thyroid cancer, the most common endocrine malignancy, is often detected in young female patients. Therefore, pregnancy following thyroid cancer is not infrequent, and about 10% of thyroid cancers occurring during the reproductive years are diagnosed during pregnancy or in the early post-partum period. Differentiated thyroid cancer (DTC) in young people generally has an excellent prognosis, and disease-free survival among women with DTC diagnosed during pregnancy may not differ from that in age-matched non-pregnant women with similar disease. However, thyroid cancer detected during pregnancy may cause anxiety about the optimal timing of recommended treatments and about both maternal and neonatal morbidity, as weel as pregnancy following a diagnosis of thyroid cancer obviously needs both maternal and foetal management. The main objectives in clinical monitoring of pregnant thyroid cancer patients are: 1) to reach an adequate balance of maternal calcium and thyroid hormones that is absolutely required by the foetal central nervous system for normal maturation; 2) to maintain optimal levels of maternal thyroxin to avoid possible recurrence or spread of disease; and 3) to perform safe follow-up visits for the mother and to plan further therapy when needed. Data from a review of the literature and the authors' own experience show that in patients undergoing either suppressive or substitutive thyroxine therapy foetal thyroid growth is normal at ultrasound study, newborn thyroid status is normal, and the incidence of maternal morbidity is not influenced by the pregnancy. In this review, the authors underline that regular adjustment of levo-thyroxine and calcium therapy is of outmost importance for both maternal and foetal well-being and offer some insight, very interesting from a practical point of view, to provide a clear and simple pathway for the management of pregnancy-associated thyroid cancer. PMID- 22323847 TI - Overlay versus underlay myringoplasty: report of outcomes considering closure of perforation and hearing function. AB - In this series of patients, the underlay or overlay positioning of a graft achieves successful outcome for both repair of perforation and hearing function, with better hearing gain in the underlay group. In myringoplasty, the two most common techniques for positioning the graft relative to the remnant of both the tympanic membrane and the annulus are the "overlay" and the "underlay" techniques. 115 patients who underwent myringoplasty for tympanic membrane perforation secondary to chronic otitis media and/or trauma were included, and hearing function was evaluated. We prefer an overlay technique in subtotal perforations, in those involving the anterior and antero-inferior parts of the ear drum with respect to the handle of the malleus and in revision surgery. We reserve an underlay technique for smaller perforations and for those limited to the posterior part of the tympanic membrane. Of 115 cases, 63 underwent an overlay myringoplasty and 52 underlay myringoplasty. In the former group, five cases were anatomically unsuccessful, whereas in the second group there were three failures. The air bone gap improved significantly in both groups with a better hearing gain in the underlay group. PMID- 22323848 TI - Clinico-pathological profile of sinonasal masses: a study from a tertiary care hospital of India. AB - The present study examined the clinico-pathological profile of sinonasal masses in patients attending an Ear Nose Throat clinic of a rural tertiary care hospital of western Maharashtra in India, between May 2007 to June 2009. During the study period, 112 patients presented with sinonasal masses (male 68, female 44; age group 8-70 years). Nasal polyploid masses were non-neoplastic in 80 (71.4%) subjects, and neoplastic in 32 (28.6%) cases. Nasal obstruction was the most common (97.3%) presenting complaint, followed by rhinorrhoea (49.1%), hyposmia (31.25%), intermittent epistaxis (17.9%), headache (16.9%), facial swelling (11.6%) and eye-related symptoms (10.7%). The most common site of origin of polyploid masses was the middle meatus (54.4%) followed by the lateral wall of the nasal cavity (16.1%) and superior meatus (10.7%). Unilateral nasal masses was present in 47.7% patients, while the remaining patients had bilateral nasal masses. Allergic (62.5%) and inflammatory (25%) polyps were the most common non neoplastic mass. Haemangioma (47.3%) and inverted papilloma (36.8%) were most common benign neoplastic mass; 92.3% of all malignant masses were squamous cell carcinoma. Surgery was the major mode of treatment. It included Caldwell-Luc operation (7.1%), polypectomy (17.8%), excision of mass (25.0%) and functional endoscopic sinus surgery (44.6%). Malignancies were treated with radiotherapy. PMID- 22323849 TI - Vestibular and stabilometric findings in whiplash injury and minor head trauma. AB - Vertigo and postural instability following whiplash and/or minor head injuries is very frequent. According to some authors, post-whiplash vertigo cannot be caused by real injury to vestibular structures; other authors maintain that vestibular damage is possible even in the case of isolated whiplash, with vascular or post traumatic involvement. Furthermore, many of the balance disorders reported after trauma can be justified by post-traumatic modification to the cervical proprioceptive input, with consequent damage to the vestibular spinal reflex. The aim of this study was to evaluate the vestibular condition and postural status in a group of patients (Group A, n = 90) affected with balance disorders following whiplash, and in a second group (Group B, n = 20) with balance disorders after minor head injury associated with whiplash. Both groups were submitted to videonystagmography (VNG) and stabilometric investigation (open eyes - O E, closed eyes - CE, closed eyes with head retroflexed - CER) within 15 days of their injuries and repeated within 10 days after conclusion of cervical physiotherapy treatment. The VNG tests revealed vestibulopathy in 19% of cases in Group A (11% peripheral, 5% central, 3% in an undefined site) and in 60% of subjects in Group B (50% peripheral, 10% central). At the follow-up examination, all cases of non-compensated labyrinth deficit showed signs of compensation, while there were two cases (2%) in Group A and one case (5%) in Group B of PPV. As far as the altered posturographic recordings are concerned, while there was no specific pattern in the two groups, they were clearly pathologic, especially during CER. Both in OE and in CE there was an increase in the surface values and in those pertaining to shifting of the gravity centre on the sagittal plane, which was even more evident during CER. In Group A, the pre-post-physiotherapy comparison of CER results showed that there was a statistically significant improvement in the majority of the parameters after treatment. Moreover, in Group B there was frequent lateral shifting of the centre of gravity that was probably linked with the high percentage of labyrinth deficits. The comparison between the first and second stabilometric examinations was statistically significant only in those parameters referring to gravity centre shifting on the frontal plane, which was probably due to the progressive improvement in the associated vestibulopathy rather than to the physiotherapy treatment performed for the cervical damage. Hence, our study confirms that only in a minority of cases can whiplash cause central or peripheral vestibulopathy, and that this is more probable after minor head injury associated with whiplash. In addition, our data confirm that static stabilometry is fundamental for assessing postural deficits following a cervical proprioceptive disorder. In these cases, in fact, analysis of the different parameters and the indices referring to cervical interference not only permits evaluation of altered postural performance, but also detects and quantifies destabilisation activity within the cervical proprioceptive component. PMID- 22323850 TI - The natural evolution of endoscopic approaches in skull base surgery: robotic assisted surgery? AB - The current surgical trend is to expand the variety of minimally invasive approaches and, in particular, the possible applications of robotic systems in head and neck surgery. This is particularly intriguing in skull base regions. In this paper, we review the current literature and propose personal considerations on the role of robotic techniques in this field. A brief description of our personal preclinical experience on skull base robotic dissection represents the basis for further considerations. We are convinced that the advantages of robotic surgery applied to the posterior cranial fossa are similar to those already clinically experienced in other areas (oropharynx, tongue base), in terms of tremor-free, bimanual, precise dissection: the implementation of instruments for bony work and resolving current drawbacks will definitely increase the applicability of such a system in forthcoming years. PMID- 22323851 TI - Role of H.E.L.P.-apheresis in the treatment of sudden sensorineural hearing loss in a group of 230 patients. PMID- 22323852 TI - Late recovery with cyclosporine-A of an auto-immune sudden sensorineural hearing loss. AB - Sensorineural hearing loss of immune-mediated origin may be present as a symptom in systemic autoimmune diseases or may occur as a primary disorder without other organ involvement (auto-immune inner ear disease). The diagnosis of auto-immune inner ear disease is still predicated on clinical features and to date specific diagnostic tests are not available. We report a case of right-sided sudden hearing loss in a female patient in which the clinical manifestations, in addition to ANA positivity and hypocomplementaemia allowed us to hypothesize an auto-immune inner ear disease. The immunosuppressive treatment with cyclosporine A was capable of a recovery of the hearing that, however, occurred progressively with normalization of the hearing function after 1 year of treatment. cyclosporine-A could be proposed as a therapeutic option in case of auto-immune inner ear disease allowing the suspension of corticosteroids that, at high dose, expose patients to potentially serious adverse events. PMID- 22323854 TI - The Transmission of Values to School-Age and Young Adult Offspring: Race and Gender Differences in Parenting. AB - The current study explores parental socialization practices and the values transmitted to school-aged and young adult off-spring, focusing on race and gender issues involved in parental teachings. A community sample of 187 black and white mothers and fathers were interviewed with regards to their parenting practices using both quantitative and qualitative approaches. Higher levels of social concern and other-oriented themes in teachings were found among black parents, in contrast to a higher prevalence of individualistic themes among white parents. Interactions with child gender and age revealed that parents were more likely to mention individualistic skills and less likely to mention concern for others to older rather than younger daughters, with a reverse pattern found for sons. Parents remain active teachers in the lives of their children beyond the first and second decades of life, instilling skills and values shaped by ethnicity and gender. Comparison of socialization practices between racial groups reveals a notable capacity of black parents to promote personal development as well as societal well-being. PMID- 22323855 TI - Acute oral poisoning due to chloracetanilide herbicides. AB - Chloracetanilide herbicides (alachlor, butachlor, metachlor) are used widely. Although there are much data about chronic low dose exposure to chloracetanilide in humans and animals, there are few data about acute chloracetanilide poisoning in humans. This study investigated the clinical feature of patients following acute oral exposure to chloracetanilide. We retrospectively reviewed the data on the patients who were admitted to two university hospitals from January 2006 to December 2010. Thirty-five patients were enrolled. Among them, 28, 5, and 2 cases of acute alachlor, metachlor, butachlor poisoning were included. The mean age was 49.8 +/- 15.4 yr. The poison severity score (PSS) was 17 (48.6%), 10 (28.6%), 5 (14.3%), 2 (5.7%), and 1 (2.9%) patients with a PSS of 0, 1, 2, 3, and 4, respectively. The age was higher for the symptomatic patients (1-4 PSS) than that for the asymptomatic patients (0 PSS) (43.6 +/- 15.2 vs 55.7 +/- 13.5). The arterial blood HCO3- was lower in the symptomatic patients (1-4 PSS) than that in the asymptomatic patients (0 PSS). Three patients were a comatous. One patient died 24 hr after the exposure. In conclusion, although chloracetanilide poisoning is usually of low toxicity, elder patients with central nervous system symptoms should be closely monitored and cared after oral exposure. PMID- 22323856 TI - Kidney transplantation from a donor following cardiac death supported with extracorporeal membrane oxygenation. AB - To expand the donor pool, organ donation after cardiac death (DCD) has emerged. However, kidneys from DCD donors have a period of long warm ischemia between cardiac arrest and the harvesting of the organs. Recently, we used extracorporeal membrane oxygenation (ECMO) to minimize ischemic injury during 'no touch' periods in a Maastricht category II DCD donor and performed two successful kidney transplantations. The kidneys were procured from a 49-yr-old male donor. The warm ischemia time was 31 min, and the time of maintained circulation using ECMO was 7 hr 55 min. The cold ischemia time was 9 hr 15 min. The kidneys were transplanted into two recipients and functioned immediately after reperfusion. The grafts showed excellent function at one and three months post-transplantation; serum creatinine (SCr) levels were 1.0 mg/dL and 0.8 mg/dL and the estimated glomerular filtration rates (eGFR) were 63 mL/min/1.73 m(2) and 78 mL/min/1.73 m(2) in the first recipient, and SCr levels were 1.1 mg/dL and 1.0 mg/dL and eGFR were 56 mL/min/1.73 m(2) and 64 mL/min/1.73 m(2) in the second recipient. In conclusion, it is suggested that kidney transplantation from a category II DCD donor assisted by ECMO is a reasonable modality for expanding donor pool. PMID- 22323857 TI - Factors affecting the prescribing patterns of antibiotics and injections. AB - There are serious problems concerning the inadequate prescription of antibiotics and overuse of injections in primary care. However, the determinants of prescription patterns in Korea are not well-documented. To examine the area characteristics affecting the prescription of antibiotics and injections in primary care practices in the treatment of respiratory tract infections (RTIs), a nationwide cross-sectional study was performed in all 250 administrative districts of Korea. The outcome was modeled as a binary variable: over prescription or not compared with the nation-wide average. Over-prescription of antibiotics was associated with the ratio of specialists to general physicians and over-prescription in previous years in the area (adjusted odds ratio [aOR], 4.8; 95% confidence interval [CI] 1.5-14.8; and aOR, 12.0; 95% CI 5.5-25.9, respectively). Over-use of injections was associated with younger population, urban living and the number of hospital beds in the area (aOR, 0.2; 95% CI 0.1 0.4; aOR, 0.3; 95% CI 0.1-0.8; and aOR, 0.4, 95% CI 0.2-0.9; respectively). There were differences in the prescribing patterns in different districts; prescription patterns were affected more by supply factors than by demand factors. Highly competitive medical environment associated with supply factors is a significant determinant of prescription patterns in Korea. PMID- 22323858 TI - Pathophysiological role of hormones and cytokines in cancer cachexia. AB - We investigated the role of fasting hormones and pro-inflammatory cytokines in cancer patients. Hormones (ghrelin, adiponectin, and leptin) and cytokines (TNF alpha, IFN-gamma, and IL-6) were measured by ELISA or RIA in lung cancer and colorectal cancer patients before the administration of cancer therapy, and measurements were repeated every 2 months for 6 months. From June 2006 to August 2008, 42 patients (19 with colorectal cancer and 23 with lung cancer) were enrolled. In total, 21 patients were included in the cachexia group and the others served as a comparison group. No significant difference in the initial adiponectin, ghrelin, TNF-alpha, IFN-gamma, or IL-6 level was observed between groups, although leptin was significantly lower in cachectic patients than in the comparison group (15.3 +/- 19.5 vs 80.9 +/- 99.0 pg/mL, P = 0.007). During the follow-up, the patients who showed a > 5% weight gain had higher ghrelin levels after 6 months. Patients exhibiting elevated IL-6 levels typically showed a weight loss > 5% after 6 months. A blunted adiponectin or ghrelin response to weight loss may contribute to cancer cachexia and IL-6 may be responsible for inducing and maintaining cancer cachexia. PMID- 22323859 TI - Tandem high-dose chemotherapy and autologous stem cell transplantation in young children with atypical teratoid/rhabdoid tumor of the central nervous system. AB - The feasibility and effectiveness of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) were evaluated in children younger than 3 yr of age with atypical teratoid/rhabdoid tumors (ATRT). Tandem HDCT/autoSCT was administered following six cycles of induction chemotherapy. Radiotherapy (RT) was administered if the tumor relapsed or progressed, otherwise, it was administered after 3 yr of age. Tumors relapsed or progressed during induction chemotherapy in 5 of 9 patients enrolled; 3 of these 5 received tandem HDCT/autoSCT as a salvage treatment. One patient died from sepsis during induction chemotherapy. The remaining 3 patients proceeded to tandem HDCT/autoSCT; however, 2 of these patients showed tumor relapse/progression after tandem HDCT/autoSCT. All 7 relapses/progressions occurred at primary sites even in patients with leptomeningeal seeding. Toxicities during tandem HDCT/autoSCT were manageable. A total of 5 patients were alive with a median follow-up of 20 (range 16-70) months from diagnosis. Four of 5 patients who received RT after relapse/progression are alive. The probability of overall survival at 3 yr from diagnosis was 53.3% +/- 17.3%. Our tandem HDCT/autoSCT is feasible; however, early administration of RT prior to tandem HDCT/autoSCT should be considered to improve the outcome after tandem HDCT/autoSCT. PMID- 22323860 TI - Telomerase activity and the risk of lung cancer. AB - Telomerase play a key role in the maintenance of telomere length and chromosome integrity. We have evaluated the association between telomerase activity and the risk of lung cancer in peripheral blood. Telomerase activity in peripheral blood mononuclear cells was measured by a PCR-designed telomeric repeat amplification protocol in 63 lung cancer patients and 190 healthy controls that were matched for age, gender, and smoking status. Telomerase activity was significantly lower in the lung cancer patients than in controls (mean +/- standard deviation; 1.32 +/- 1.65 vs 2.60 +/- 3.09, P < 1 * 10(-4)). When telomerase activity was categorized into quartiles based on telomerase activity in the controls, the risk of lung cancer increased as telomerase activity reduced (P(trend) = 1 * 10(-4)). Moreover, when the subjects were categorized based on the median value of telomerase activity, subjects with low telomerase activity were at a significantly increased risk of lung cancer compared to subjects with high telomerase activity (adjusted odds ratio = 3.05, 95% confidence interval = 1.60 5.82, P = 7 * 10(-4)). These findings suggest that telomerase activity may affect telomere maintenance, thereby contributing to susceptibility to lung cancer. PMID- 22323861 TI - Improving survival rate of patients with in-hospital cardiac arrest: five years of experience in a single center in Korea. AB - The aim of this study was to describe the cause of the recent improvement in the outcomes of patients who experienced in-hospital cardiac arrest. We retrospectively analyzed the in-hospital arrest registry of a tertiary care university hospital in Korea between 2005 and 2009. Major changes to the in hospital resuscitation policies occurred during the study period, which included the requirement of extensive education of basic life support and advanced cardiac life support, the reformation of cardiopulmonary resuscitation (CPR) team with trained physicians, and the activation of a medical emergency team. A total of 958 patients with in-hospital cardiac arrest were enrolled. A significant annual trend in in-hospital survival improvement (odds ratio = 0.77, 95% confidence interval 0.65-0.90) was observed in a multivariate model. The adjusted trend analysis of the return of spontaneous circulation, six-month survival, and survival with minimal neurologic impairment upon discharge and six-months afterward revealed similar results to the original analysis. These trends in outcome improvement throughout the study were apparent in non-ICU (Intensive Care Unit) areas. We report that the in-hospital survival of cardiac arrest patients gradually improved. Multidisciplinary hospital-based efforts that reinforce the Chain of Survival concept may have contributed to this improvement. PMID- 22323862 TI - Long term results of ST-segment elevation myocardial infarction versus non-ST segment elevation myocardial infarction after off-pump coronary artery bypass grafting: propensity score matching analysis. AB - There is no consensus as to which acute myocardial infarction subtype poses a greater risk after coronary artery bypass grafting (CABG). We compared the early and the long term results of off-pump coronary artery bypass grafting (OPCAB) between patients with STEMI (group I, n = 83), and NSTEMI (group II, n = 237). Group I had higher EuroSCORE, prevalence of emergency surgery, preoperative intra aortic balloon pump use, preoperative emergency percutaneous transluminal coronary angioplasty, and preoperative thrombolytic use than group II. There were no significant differences in 30-day mortality and major adverse cardiac and cerebrovascular event (MACCE) between groups. Overall 8-yr survival was 93% and 87% in groups I and II, respectively. Freedom from MACCE after 8 yr was 92% and 93% in groups I and II, respectively. After propensity score matching analysis, there were no significant differences in preoperative parameters, postoperative in-hospital outcomes, and long-term clinical outcomes. Surgical results of OPCAB in patients with acute myocardial infarction show good results in terms of long term survival and freedom from MACCE, with no significant differences in clinical outcomes between STEMI and NSTEMI groups. PMID- 22323863 TI - Comparison of early and late conversion of sirolimus in experimental model of chronic cyclosporine nephropathy. AB - Sirolimus (SRL) is a promising drug for replacing calcineurin inhibitors. We performed this study to determine the optimal time of conversion from cyclosporine (CsA) to SRL in an experimental model of chronic CsA nephropathy. Three separate studies were performed. In the first study, SRL was given to rats with or without CsA for 4 weeks. In the second study, rats were treated initially with CsA for 1 week, and then switched to SRL (early conversion). In the third study, CsA was given for 4 weeks and then replaced by SRL for 4 weeks treatment of CsA (late conversion). The influence of SRL on CsA-induced renal injury was evaluated by assessing renal function, histopathology (interstitial inflammation and fibrosis), and apoptotic cell death. Combined CsA and SRL treatment significantly impaired renal function, increased apoptosis, and interstitial fibrosis and inflammation compared with CsA or SRL treatment alone. Early conversion to SRL did not change renal function, histopathology, or apoptosis compared with early CsA withdrawal. By contrast, late conversion to SRL significantly aggravated these parameters compared with late CsA withdrawal. In conclusion, early conversion from CsA to SRL is effective in preventing CsA induced renal injury in a setting of CsA-induced renal injury. PMID- 22323864 TI - Outcome of early initiation of peritoneal dialysis in patients with end-stage renal failure. AB - Recent studies reported that early initiation of hemodialysis may increase mortality. However, studies that assessed the influence of early initiation of peritoneal dialysis (PD) yielded controversial results. In the present study, we evaluated the prognosis of early initiation of PD on the various outcomes of end stage renal failure patients by using propensity-score matching methods. Incident PD patients (n = 491) who started PD at SNU Hospital were enrolled. The patients were divided into 'early starters (n = 244)' and 'late starters (n = 247)' on the basis of the estimated glomerular filtration rate (eGFR) at the start of dialysis. The calculated propensity-score was used for one-to-one matching. After propensity-score-based matching (n = 136, for each group), no significant differences were observed in terms of all-cause mortality (P = 0.17), technique failure (P = 0.62), cardiovascular event (P = 0.96) and composite event (P = 0.86) between the early and late starters. Stratification analysis in the propensity-score quartiles (n = 491) exhibited no trend toward better or poorer survival in terms of all-cause mortality. In conclusion, early commencement of PD does not reduce the mortality risk and other outcomes. Although the recent guidelines suggest that initiation of dialysis at higher eGFR, physicians should not determine the time to initiate PD therapy simply rely on the eGFR alone. PMID- 22323865 TI - The ability of beta-cells to compensate for insulin resistance is restored with a reduction in excess growth hormone in Korean acromegalic patients. AB - The aim of this study was to assess the prevalence of diabetes and to study the effects of excess growth hormone (GH) on insulin sensitivity and beta-cell function in Korean acromegalic patients. One hundred and eighty-four acromegalic patients were analyzed to assess the prevalence of diabetes, and 52 naive acromegalic patients were enrolled in order to analyze insulin sensitivity and insulin secretion. Patients underwent a 75 g oral glucose tolerance test with measurements of GH, glucose, insulin, and C-peptide levels. The insulin sensitivity index and beta-cell function index were calculated and compared according to glucose status. Changes in the insulin sensitivity index and beta cell function index were evaluated one to two months after surgery. Of the 184 patients, 17.4% were in the normal glucose tolerance (NGT) group, 45.1% were in the pre-diabetic group and 37.5% were in the diabetic group. The insulin sensitivity index (ISI(0,120)) was significantly higher and the HOMA-IR was lower in the NGT compared to the diabetic group (P = 0.001 and P = 0.037, respectively). The ISI(0,120) and disposition index were significantly improved after tumor resection. Our findings suggest that both insulin sensitivity and beta-cell function are improved by tumor resection in acromegalic patients. PMID- 22323866 TI - Comparison of visceral fat and liver fat as risk factors of metabolic syndrome. AB - The principal objective of this study was to determine whether visceral fat or liver fat is a more relevant risk factor for metabolic syndrome. A total of 98 subjects aged 18-65 yr, who visited a health promotion center in a university hospital, were enrolled in this study. Metabolic syndrome was diagnosed based on the modified National Cholesterol Education Program's Adult Treatment Panel III report (NCEP-ATPIII) criteria. We defined the visceral obesity as a visceral fat area of >= 100 cm(2) which was acquired by CT at the L4-5 level. To evaluate fatty liver, we applied a liver-to-spleen attenuation ratio <= 1.1 as measured by CT at the T12 level. We employed binary logistic regression models that used the presence or absence of metabolic syndrome as a dependent variable and age, sex, and the presence or absence of visceral obesity and fatty liver as independent variables. Visceral obesity was not found to be an independent variable as a risk factor of metabolic syndrome (odds ratio 2.7; 95% confidence interval 0.55 13.30), but fatty liver was found to be significant in this model (odds ratio 71.3; 95% CI 13.04-389.53). Our study suggests that liver fat may be a more important risk factor than visceral fat in terms of its association with metabolic syndrome. PMID- 22323867 TI - Relationship between Helicobacter pylori virulence genes and clinical outcomes in Saudi patients. AB - Helicobacter pylori has been strongly associated with gastritis, gastric and duodenal ulcers, and it is a risk factor for gastric cancer. Two major virulence factors of H. pylori have been described: the cytotoxin-associated gene product (cagA) and the vacuolating toxin (vacA). Since considerable geographic diversity in the prevalence of H. pylori virulence factors has been reported, the aim of this work was to determine if there is a significant correlation between different H. pylori virulence genes (cagA and vacA) in 68 patients, from Saudi Arabia, and gastric clinical outcomes. H. pylor was recognized in cultures of gastric biopsies. vacA and cagA genes were detected by polymerase chain reaction (PCR). The cagA gene was obtained with 42 isolates (61.8%). The vacA s- and m- region genotypes were determined in all strains studied. Three genotypes were found: s1/m1 (28%), s1/m2 (40%) and s2/m2 (26%). The s2/m1 genotype was not found in this study. The relation of the presence of cagA and the development of cases to gastritis and ulcer was statistically significant (P < 0.05). The study showed a significant correlation between the vacAs1/m2 genotype and gastritis cases, and a significant correlation between vacAs1/m1 genotype and peptic ulcer cases. The results of this study might be used for the identification of high-risk patients who are infected by vacAs1/m1 genotype of H. pylori strains. In conclusion, H. pylori strains of vacA type s1 and the combination of s1/m1 were associated with peptic ulceration and the presence of cagA gene. PMID- 22323868 TI - Factors to predict positive results of gonadotropin releasing hormone stimulation test in girls with suspected precocious puberty. AB - Sometimes, the clinical findings and the results of the gonadotropin-releasing hormone (GnRH) stimulation test are inconsistent in girls with early breast development and bone age advancement. We aimed to investigate the factors predicting positive results of the GnRH stimulation test in girls with suspected central precocious puberty (CPP). We reviewed the records of 574 girls who developed breast budding before the age of 8 yr and underwent the GnRH stimulation test under the age of 9 yr. Positive results of the GnRH stimulated peak luteinizing hormone (LH) level were defined as 5 IU/L and over. Girls with the initial positive results (n = 375) showed accelerated growth, advanced bone age and higher serum basal LH, follicle-stimulating hormone, and estradiol levels, compared to those with the initial negative results (n = 199). Girls with the follow-up positive results (n = 64) showed accelerated growth and advanced bone age, compared to those with the follow-up negative results. In the binary logistic regression, the growth velocity ratio was the most significant predictive factor of positive results. We suggest that the rapid growth velocity is the most useful predictive factor for positive results in the GnRH stimulation test in girls with suspected precocious puberty. PMID- 22323869 TI - Oral solubilized ursodeoxycholic acid therapy in amyotrophic lateral sclerosis: a randomized cross-over trial. AB - To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) with oral solubilized formula in amyotrophic lateral sclerosis (ALS) patients, patients with probable or definite ALS were randomized to receive oral solubilized UDCA (3.5 g/140 mL/day) or placebo for 3 months after a run-in period of 1 month and switched to receive the other treatment for 3 months after a wash-out period of 1 month. The primary outcome was the rate of progression, assessed by the Appel ALS rating scale (AALSRS), and the secondary outcomes were the revised ALS functional rating scale (ALSFRS-R) and forced vital capacity (FVC). Fifty-three patients completed either the first or second period of study with only 16 of 63 enrolled patients given both treatments sequentially. The slope of AALSRS was 1.17 points/month lower while the patients were treated with UDCA than with placebo (95% CI for difference 0.08-2.26, P = 0.037), whereas the slopes of ALSFRS-R and FVC did not show significant differences between treatments. Gastrointestinal adverse events were more common with UDCA (P < 0.05). Oral solubilized UDCA seems to be tolerable in ALS patients, but we could not make firm conclusion regarding its efficacy, particularly due to the high attrition rate in this cross-over trial. PMID- 22323870 TI - A case of isolated light chain deposition disease in the duodenum. AB - Light chain deposition disease (LCDD) is a rare disorder associated with a clonal proliferation of plasma cells, which synthesize abnormal monoclonal immunoglobulin light chains. LCDD is characterized by systemic deposition of light chains in various organs, with the kidneys being most commonly affected. There have been few reports of isolated LCDD. We report a rare case of LCDD limited to a duodenal polyp. A 63-yr-old man visited our hospital for health screening without symptoms in 2009. On gastrofiberscopy, a duodenal polyp was observed. The biopsy showed diffuse infiltration by atypical plasma cells, which were positive for kappa-type light chains by immunohistochemistry. While the patient refused further management, we could find no evidence of recurrence until 2 yr after the initial diagnosis. It has been reported that isolated LCDD has relatively good prognosis compared to systemic LCDD. However, treatment for this disease has not been established yet. PMID- 22323871 TI - Unilateral pulmonary edema: a rare initial presentation of cardiogenic shock due to acute myocardial infarction. AB - Cardiogenic unilateral pulmonary edema (UPE) is a rare clinical entity that is often misdiagnosed at first. Most cases of cardiogenic UPE occur in the right upper lobe and are caused by severe mitral regurgitation (MR). We present an unusual case of right-sided UPE in a patient with cardiogenic shock due to acute myocardial infarction (AMI) without severe MR. The patient was successfully treated by percutaneous coronary intervention and medical therapy for heart failure. Follow-up chest Radiography showed complete resolution of the UPE. This case reminds us that AMI can present as UPE even in patients without severe MR or any preexisting pulmonary disease affecting the vasculature or parenchyma of the lung. PMID- 22323872 TI - Radiofrequency catheter ablation of hemodynamically unstable ventricular tachycardia associated with systemic sclerosis. AB - Systemic sclerosis (SS) is a connective tissue disease and cardiac involvement is common. Primary cardiac involvement such as conduction system disturbances and arrhythmias can also occur. However, reports of sustained ventricular tachycardia (VT) are rare. We report a case of catheter ablation of sustained ventricular tachycardia in a patient with systemic sclerosis using a conventional mapping system. A 64-yr-old woman with a 10-yr history of SS was referred for management of her ventricular tachycardia. There was no structural abnormality in cardiac chambers. However, electrophysiologic study revealed electrical substrate of ventricular tachycardia which could be ablated with pacemapping and substrate mapping. This case demonstrated successful conventional mapping and catheter ablation in a hemodynamically unstable patient with SS. PMID- 22323873 TI - A case of severe acute kidney injury by near-drowning. AB - Acute kidney injury (AKI) secondary to near-drowning is rarely described and poorly understood. Only few cases of severe isolated AKI resulting from near drowning exist in the literature. We report a case of near-drowning who developed to isolated AKI due to acute tubular necrosis (ATN) requiring dialysis. A 21-yr old man who recovered from near-drowning in freshwater 3 days earlier was admitted to our hospital with anuria and elevated level of serum creatinine. He needed five sessions of hemodialysis and then renal function recovered spontaneously. Renal biopsy confirmed ATN. We review the existing literature on near-drowning-induced AKI and discuss the possible pathogenesis. PMID- 22323874 TI - Severe osteomyelitis as a complication of Tokyo-172 BCG vaccination. AB - The bacilli Calmette-Guerin (BCG) Tokyo-172 strain was considered to exhibit good protective efficacy with a low rate of unfavorable side effects. However, we describe a rare case of BCG osteomyelitis developed in an immunocompetent host who was given with BCG Tokyo-172 vaccine on the left upper arm by multipuncture method. A 9-month-old girl presented with progressive inability to move her right elbow and had radiographic evidence of septic elbow combined with osteomyelitis of right distal humerus. A biopsy from the site revealed chronic caseating granulomatous inflammation, positive for BCG Tokyo-172 strain on the multiplex polymerase chain reaction. The child had to undergo second surgical debridements and oral antituberculosis chemotherapy. There were no sequelae after 2 yr of follow-up. This complication, although uncommon, should be considered in the appropriate clinical setting. PMID- 22323875 TI - Hereditary sclerosing poikiloderma. AB - Hereditary sclerosing poikiloderma (HSP) is a very rare disease. The clinical features are principally widespread poikiloderma and linear hyperkeratotic and sclerotic bands. We report an 18-yr-old male who presented reticular hyperpigmented lesions on the trunk and extremities since 2-yr-old. Also, linear sclerosing bands appeared on both antecubital and popliteal fossae after yr. Histopathologic finding showed dense sclerotic collagen fibers with telangiectasia in the upper dermis and fragmentations of damaged elastic fibers in the elastic stain, consistent with HSP. We report the first Korean case of HSP. PMID- 22323876 TI - EML4-ALK fusion gene in Korean non-small cell lung cancer. AB - A fusion gene between echinoderm microtubule-associated protein-like 4 (EML4) and the anaplastic lymphoma kinase (ALK) has been identified in non-small cell lung cancers (NSCLCs). Although a few studies have evaluated EML4-ALK fusion genes in Korean NSCLCs, the prevalence of different EML4-ALK fusion variants has yet to be clearly assessed. Herein, we have examined the profiles of EML4-ALK fusion gene variants in Korean patients of NSCLCs. EML4-ALK fusion genes have been detected in 10 (6.0%) of 167 patients of NSCLCs and in 9 (7.4%) of 121 patients of adenocarcinoma. Of the 10 patients with fusion genes identified, 8 (80%) were E13;A20 (variant 1) and 2 (20%) were E6;A20, with an additional 33-bp sequence derived from intron 6 of EML4 (variant 3b). These results indicate that the profiles of EML4-ALK fusion gene variants in Korean patients of NSCLC may differ from those in other ethnic populations. Herein, we describe for the first time the profiles of EML4-ALK fusion variants of Korean patients with NSCLCs. PMID- 22323877 TI - Outcomes of levator resection at tertiary eye care center in Iran: a 10-year experience. AB - PURPOSE: To assess outcomes of levator resection for the surgical correction of congenital and acquired upper lid ptosis in patients with fair to good levator function and evaluation of the relationship between demographic data and success of this operation. METHODS: In a retrospective study, medical records of patients with blepharoptosis who had undergone levator resection over a 10-year period and were followed for at least 3 months were reviewed. RESULTS: Overall, 136 patients including 60 (44.1%) male and 76 (55.9%) female subjects with a mean age of 20 +/ 13.8 years (range, 2 to 80 years) were evaluated, of whom 120 cases (88.2%) had congenital ptosis and the rest had acquired ptosis. The overall success rate after the first operation was 78.7%. The most common complication after the first operation was undercorrection in 26 cases (19.1%), which was more prevalent among young patients (p = 0.06). Lid fissure and margin reflex distance (MRD(1)) also increased after levator resection (p < 0.001). Age, sex, type of ptosis, amblyopia, levator function, MRD(1), lid fissure and spherical equivalent were not predictive of surgical outcomes of levator resection. CONCLUSIONS: Levator resection has a high rate of success and few complications in the surgical treatment of congenital and acquired upper lid ptosis with fair to good levator function. Reoperation can be effective in most cases in which levator resection has been performed. PMID- 22323878 TI - Posterior corneal curvature assessment after Epi-LASIK for myopia: comparison of Orbscan II and Pentacam imaging. AB - PURPOSE: To compare the changes in posterior corneal curvature using scanning slit topography (Orbscan II) and Scheimpflug imaging (Pentacam) before and after Epi-laser in situ keratomileusis (LASIK) for myopia. METHODS: In a prospective observational case-series study, 20 myopic patients having undergone Epi-LASIK were examined serially with two different devices, Orbscan II and Pentacam, preoperatively and one month postoperatively. Posterior central elevation (PCE) and posterior maximal elevation (PME) were compared between the two devices, and the changes in parameters after Epi-LASIK were analyzed using a difference map. RESULTS: All parameters (preoperative and postoperative PCE and preoperative and postoperative PME) that were measured using the Orbscan II were significantly greater compared to those of the Pentacam (for all p < 0.001). PCE and PME were significantly increased one month postoperatively in the Orbscan II measurements (p < 0.05) but were not significantly increased in the Pentacam measurements. Also, DeltaPCE and DeltaPME, in the difference map obtained by each serial scanning, were significantly greater in the Orbscan II measurements than with the Pentacam (p = 0.012, p = 0.016). CONCLUSIONS: The Pentacam measurements displayed significantly reduced values in all parameters related to posterior corneal elevation compared to those of the Orbscan II. The Pentacam showed no significant change in posterior corneal curvature after Epi-LASIK, based on the difference map. PMID- 22323879 TI - Which keratometer is most reliable for correcting astigmatism with toric intraocular lenses? AB - PURPOSE: To evaluate the accuracy of preoperative keratometers used in cataract surgery with toric intraocular lens (IOL). METHODS: Twenty-five eyes received an AcrySof toric IOL implantation. Four different keratometric methods, a manual keratometer, an IOL master, a Pentacam and an auto keratometer, were performed preoperatively in order to evaluate preexisting corneal astigmatism. Differences between the true residual astigmatism and the anticipated residual astigmatism (keratometric error) were compared at one and three months after surgery by using a separate vector analysis to identify the keratometric method that provided the highest accuracy for astigmatism control. RESULTS: The mean keratomeric error was 0.52 diopters (0.17-1.17) for the manual keratometer, 0.62 (0-1.31) for the IOL master, 0.69 (0.08-1.92) for the Pentacam, and 0.59 (0.08-0.94) for the auto keratometer. The manual keratometer was the most accurate, although there was no significant difference between the keratometers (p > 0.05). All of the keratometers achieved an average keratometric error of less than one diopter. CONCLUSIONS: Manual keratometry was the most accurate of the four methods evaluated, although the other techniques were equally satisfactory in determining corneal astigmatism. PMID- 22323880 TI - Clinical characteristics of polypoidal choroidal vasculopathy associated with chronic central serous chorioretionopathy. AB - PURPOSE: To investigate the clinical characteristics of polypoidal choroidal vasculopathy (PCV) associated with chronic central serous chorioretinopathy (CSC). METHODS: We retrospectively reviewed the medical records of 246 PCV patients (283 eyes) between July 2004 and August 2009 and investigated the clinical characteristics of the PCV patients who had specific fundus findings of chronic CSC. RESULTS: Among PCV patients, 13 eyes (4.6%) of 13 PCV patients (5.3%) had fundus findings of chronic CSC. All of the PCV lesions had a solitary polyp located outside the atrophic retina, predominantly in the macular area (84.6%), most showed an exudative pattern (69.2%) and there were a few that showed a hemorrhagic pattern (30.8%). All of the lesions were smaller than 1 disc diameter. Most of the PCV lesions (76.9%) were cured with less than two treatments in a short period of 6.4 +/- 1.9 months; however, visual acuity deteriorated (61.5%) or was not changed (30.8%) in most of the cases. CONCLUSIONS: The PCV associated with chronic CSC had several clinical features such as a small exudative retinal lesion with a solitary polyp and frequent involvement of the macular area. Even though there was poor visual outcome due to the atrophic change, all of the PCV lesions were easily resolved in a short period with a simple treatment course and no recurrence. PMID- 22323881 TI - Clinical outcomes of cyclosporine treatment for noninfectious uveitis. AB - PURPOSE: To assess the clinical outcomes of cyclosporine treatment for noninfectious uveitis. METHODS: A retrospective review of medical records was completed for 182 noninfectious uveitis patients who were treated with cyclosporine between January 2001 and August 2010. Data was obtained relevant to demographic characteristics, anatomic classification, and laterality of uveitis, associated systemic disorder, dosage of cyclosporine and prednisolone, usage of other immunosuppressive drugs, visual acuity (VA), control of uveitic activity, and adverse effects during the cyclosporine use. RESULTS: Uveitic activity was controlled to a level of minimal inflammation in 89.0% and completely in 78.6% of patients by the median duration of 49 and 98 days, respectively. Prednisolone sparing (dose <=10 mg) control of inflammation equal to or less than the minimal activity was achieved in 75.3% of patients. VA was aggravated more than 0.2 logarithm of the minimum angle of resolution in 17.3% of eyes in spite of cyclosporine treatment for the mean follow-up of 698.4 days. Dose reduction and cessation of cyclosporine was required only in 3.3% and 9.3%, respectively, due to the intolerable toxicity, although 44.0% of patients experienced mild to moderate adverse effects. CONCLUSIONS: Cyclosporine combined with corticosteroids or other immunosuppressive drugs as needed is an effective treatment for noninfectious uveitis, thus minimizing the adverse effects of corticosteroids and other toxic drugs. However, careful monitoring for the toxicity of cyclosporine is needed, because a small group of patients cannot tolerate its toxicity. PMID- 22323882 TI - The efficacy of a monocular drug trial in normal-tension glaucoma. AB - PURPOSE: To evaluate the efficacy of a monocular drug trial in eyes with normal tension glaucoma (NTG). METHODS: This prospective study enrolled 74 patients with NTG. The monocular drug trial was started using latanoprost 0.005% for one week. If the intraocular pressure (IOP) reduction was greater than 15%, the same medication was administered to both eyes for one month. The unadjusted change and adjusted change (the change in the treated eye minus the change in the contralateral eye) in IOP were evaluated, and the predictors of IOP response were analyzed by multivariate linear regression. RESULTS: Among the initial 74 patients, 31 (41.9%) were included; others were excluded because they did not meet the requisite conditions. The most significant predictors of IOP response in the initial eye and subsequent eye were the baseline IOPs in both eyes (beta = 0.907, 0.771, respectively). The adjusted change in IOP of the initial eye had greater association (beta = 0.589) with the IOP after monocular trial in the initial eye than that of unadjusted IOP change (beta = 0.279). The adjusted change in IOP also had greater predictability (beta = 0.348) for IOP after monocular trial in the subsequent eye than that of the unadjusted IOP change (beta = 0.090). CONCLUSIONS: Although the monocular trial in NTG patients had limited efficacy due to its stringent conditions, it was useful for evaluating the IOP response in the initial eye and for predicting the IOP response in the subsequent eye. PMID- 22323883 TI - Retinal nerve fiber layer measurement variability with spectral domain optical coherence tomography. AB - PURPOSE: To evaluate the effect of the scanning laser ophthalmoscope (SLO) guided re-test mode on short- and long-term measurement variability of peripapillary retinal nerve fiber layer (RNFL) thickness obtained by spectral domain-SLO optical coherence tomography (SD-SLO/OCT). METHODS: Seventy five healthy eyes were scanned 3 times per day (intra-session variability) by both the SLO guided re-test mode and the independent mode of SD-SLO/OCT. Subjects were scanned 3 times by both modes at visits within a 2-week interval (inter-session variability). For testing longitudinal variability, 3 separate exams were performed over 6 months by both modes. The coefficient of variation (CV), reproducibility coefficient (RC) and intraclass correlation coefficient of RNFL thickness were compared between the two modes. RESULTS: The intra-session RC and CV ranged from 5.4 to 12.9 microns and 1.76% to 5.72% when measured by independent mode and 5.4 to 12.5 microns and 1.75% to 5.58% by re-test mode, respectively. The inter-session RC and CV ranged from 5.8 to 13.3 microns and 1.89% to 5.78% by independent mode and 5.8 to 12.7 microns and 1.90% to 5.54% by re-test mode, respectively. Intra-session and inter-session variability measurements were not significantly different between the two modes. The longitudinal RC and CV ranged from 8.5 to 19.2 microns and 2.79% to 7.08% by independent mode and 7.5 to 14.4 microns and 2.33% to 6.22% by re-test mode, respectively. Longitudinal measurement variability was significantly lower when measured by the re-test mode compared to the independent mode (average, p = 0.011). CONCLUSIONS: The SLO guided re-test mode for RNFL thickness measurement in SD-SLO/OCT employing a tracking system improved long-term reproducibility by reducing variability induced by inconsistent scan circle placement. PMID- 22323884 TI - The analysis of AC/A ratio in nonrefractive accommodative esotropia treated with bifocal glasses. AB - PURPOSE: To report the long term results of bifocal treatment in nonrefractive accommodative esotropia and to analyze the changes of accommodative convergence to accommodation (AC/A) ratio. METHODS: Sixteen patients treated with bifocal glasses for at least 5 years were evaluated retrospectively. Angle of deviation at near and distance, refractive error, and AC/A ratio by the lens gradient method were analyzed. The changes of AC/A ratios were also compared after dividing the patients according to continuation or cessation of bifocal therapy. RESULTS: Six patients (38%; bifocal stop group, BSG) were able to stop using bifocal glasses at an average age of 10.8 years (range, 6.5 to 15.4 years) during their follow-up. However, the other ten patients (62%; bifocal continue group, BCG) had to continue using bifocal glasses until the final visit, which was 13.8 years on average (range, 11.3 to 18.5 years). The AC/A ratio decreased from time of bifocal prescription to the last visit in both groups, from 4.4 to 2.7 in the BSG and from 5.9 to 4.5 in the BCG. AC/A ratios were significantly higher (p = 0.03) in the BCG than that of the BSG from the beginning of bifocal treatment and this difference was persistent until the final visit (p = 0.03). CONCLUSIONS: The AC/A ratio decreased with age in both groups but was significantly higher throughout the entire follow-up period in the BCG. AC/A ratio at bifocal prescription could be an important factor in predicting response to bifocal treatment. PMID- 22323885 TI - The role of focal adhesion kinase in the TGF-beta-induced myofibroblast transdifferentiation of human Tenon's fibroblasts. AB - PURPOSE: To investigate the role of focal adhesion kinase (FAK) in transforming growth factor (TGF)-beta-induced myofibroblast transdifferentiation of human Tenon's fibroblasts. METHODS: Primary cultured human Tenon's fibroblasts were exposed to TGF-beta1 for up to 48 hours. The mRNA levels of FAK, alpha smooth muscle actin (alphaSMA), and beta-actin were determined by quantitative real time reverse transcription polymerase chain reaction. The protein levels of collagen type I, FAK, phospho-FAK, alphaSMA, and beta-actin were determined by Western immunoblots. After the small interfering RNA targeting FAK (siRNA(FAK)) molecules were delivered into the cells, the expressions of alphaSMA proteins were determined by Western immunoblots. RESULTS: In human Tenon's fibroblasts, TGF beta1 significantly increased the mRNA and protein expressions of alphaSMA. However, when the action of FAK was inhibited using siRNA(FAK), the TGF-beta1 induced expression of alphaSMA was attenuated. CONCLUSIONS: Our data suggest that FAK may be associated with the TGF-beta1-induced transdifferentiation of human Tenon's fibroblasts to myofibroblasts, which is the essential step of subconjunctival fibrosis. PMID- 22323886 TI - Achromobacter xylosoxidans keratitis after contact lens usage. AB - To report on Achromobacter xylosoxidans keratitis in two healthy patients who had worn contact lenses foran extended period of time. A 36-year-old female and a 21 year-old female visited our hospital with ocular pain and blurred vision. Both patients had a history of wearing soft contact lenses for over fve years with occasional overnight wear. At the initial presentation, a slit lamp examination revealed corneal stromal infiltrations and epithelial defects with peripheral neovascularization in both patients. Microbiological examinations were performed from samples of corneal scrapings, contact lenses, contact lens cases, and solution. The culture resulting from the samples taken from the contact lenses, contact lens cases, and solution were all positive for Achromobacter xylosoxidans. Confrming that the direct cause of the keratitis was the contact lenses, the frst patient was prescribed ceftazidime and amikacin drops sensitive to Achromobacter xylosoxidans. The second patient was treated with 0.3% gatifoxacin and fortifed tobramycin drops. After treatment, the corneal epithelial defects were completely healed, and subepithelial corneal opacity was observed. Two cases of Achromobacter xylosoxidans keratitis were reported in healthy young females who wore soft contact lenses. Achromobacter xylosoxidans should be considered a rare but potentially harmful pathogen for lens-induced keratitis in healthy hosts. PMID- 22323887 TI - Intraocular involvement of a nasal natural killer T-cell lymphoma: a case report. AB - Herein, we report a case of nasal natural killer T-cell lymphoma (NKTL) with intraocular involvement. A 57-year-old woman was referred due to a three-day history of photophobia and diplopia in the left eye. One-month previously, she was diagnosed with nasal NKTL of the right nasal cavity. Ophthalmic examination revealed conjunctival injection and ptosis. The left pupil was fully dilated and non-reactive to light. Ocular motion was restricted on left-upper gaze. Five days later, anterior uveitis developed and persisted despite topical steroid treatment. An orbital magnetic resonance imaging was without specific findings, however, ophthalmoplegia, vitreous opacity, and an iris mass were observed. A diagnostic anterior chamber aspiration was performed. Aqueous humor aspiration revealed 35% morphologically atypical lymphocytes. After an intravitreal triamcinolone injection, radiotherapy and chemotherapy were administered; this resolved the uveitis and iris mass. When refractory uveitis or orbital pseudotumor occurs in patients with nasal NKTL, ocular and orbital involvement of the NKTL should be considered. PMID- 22323888 TI - A case of ocular toxoplasmosis imaged with spectral domain optical coherence tomography. AB - A 54-year-old man presented with blurred central vision in the right eye of two weeks' duration. On presentation, visual acuity was 40 / 50 in the right eye and fundus examination showed a whitish-yellow inflammatory lesion near an atrophic, pigmented retinochoroidal scar located in the superotemporal quadrant. Serologic assessment was negative for IgM, but serum IgG to toxoplasma was elevated. Spectral domain optical coherence tomography (SD-OCT) revealed increased reflectivity from the inner retinal layer, retinal thickening, and choroidal shadowing while focal posterior hyaloid thickening and detachment were observed in the new lesion. He was treated with trimethoprim/sulfamethoxazole, clindamycin, and prednisone. SD-OCT is helpful for definitively differentiating ocular toxoplasmosis from other retinal diseases. PMID- 22323889 TI - Resolution of recalcitrant uveitic optic disc edema following administration of methotrexate: two case reports. AB - A 13-year-old male and a 15-year-old female presented with optic disc edema associated with chronic recurrent uveitis. While the ocular inflammation responded to high doses of oral prednisolone, the disc edema showed little improvement. After oral administration of methotrexate, the disc edema and ocular inflammation were resolved, and the dose of oral corticosteroid could be reduced. PMID- 22323890 TI - Abducens nerve palsy complicated by inferior petrosal sinus septic thrombosis due to mastoiditis. AB - We present a very rare case of a 29-month-old boy with acute onset right abducens nerve palsy complicated by inferior petrosal sinus septic thrombosis due to mastoiditis without petrous apicitis. Four months after mastoidectomy, the patient fully recovered from an esotropia of 30 prism diopters and an abduction limitation (-4) in his right eye. PMID- 22323891 TI - Recession-resection surgery augmented with botulinum toxin a chemodenervation for paralytic horizontal strabismus. AB - In this case series study, we assessed the effects of recession-resection surgery augmented with botulinum toxin A chemodenervation for patients with chronic paralytic horizontal strabismus. In addition, we compared these effects with those of full tendon transposition (FTT) augmented with posterior intermuscular suture (PIMS). Ten patients who underwent strabismus surgery due to paralytic horizontal strabismus were retrospectively reviewed. They received a recession resection surgery augmented with botulinum toxin A chemodenervation (type I surgery) or a FTT augmented with PIMS (type II surgery). The preoperative angle of deviation (AOD) and postoperative improvement in AOD were compared according to the type of procedure. The preoperative AOD was 60.00 +/- 28.50 prism diopters (PD) for type I surgery and 68.00 +/- 27.06 PD for type II (p = 0.421). Improvement in AOD was 53.20 +/- 25.01 PD for type I surgery and 44.20 +/- 18.74 PD for type II (p = 0.548). Recession-resection surgery augmented with botulinum toxin A chemodenervation is a concise and effective procedure for treating paralytic horizontal strabismus. PMID- 22323892 TI - Validation of the Preschool and Early Childhood Functional Assessment Scale (PECFAS). AB - Efforts to determine the prevalence of serious emotional disturbance in preschool aged children have been hampered by the lack of a validated measure. The Preschool and Early Childhood Functional Assessment Scale (PECFAS) is a multi dimensional measure that assesses the psychosocial functioning of children aged 3 7 years. The concurrent validity and reliability of the PECFAS were assessed in a sample of 30 preschool-aged children in a large Head Start program in Ventura, California. PECFAS ratings based on in-depth interviews were significantly related to parental ratings that the children had mental health problems, psychiatric diagnoses, teacher ratings of the child's need for mental health evaluations, teacher ratings of behavior problems on a standardized screening inventory (DIAL-R), and actual referrals for mental health evaluations. Interrater reliability for the total PECFAS score was high (r = .90) as was internal consistency of the five subscales (alpha = .86). Using the PECFAS scores as a standard, the weighted prevalence of serious emotional disturbance in this West Coast Head Start program was 17%, at the lower end of the current estimated rate of SED for older children in low income samples (18-26%). PMID- 22323893 TI - Melanoma Cell Invasive and Metastatic Potential Correlates with Endothelial Cell Reorganization and Tenascin Expression. AB - A direct correlation was observed between the invasive and metastatic potential of A375 melanoma cells and their expression of tenascin and ability to support endothelial cell adhesion and reorganization. Since the ability to metastasize and establish a neovasculature requires interaction of tumor cells with extracellular matrix and endothelial cells, we examined the potential of matrix proteins synthesized by three melanoma cell lines with low-A375P, medium-A375M and high-A375SM invasive and metastatic properties to induce adhesion and rearrangement of human umbilical vein endothelial cells (HUVECs) in vitro. HUVECs adhered to and reorganized into a network of connecting and aligned cells on wells conditioned by A375SM and A375M but not A375P cells. These changes in morphology suggested differences in matrix composition among the three melanoma cell lines. In comparison to low levels of substrate-bound fibronectin and laminin, increasingly higher levels of substrate-bound tenascin were synthesized by the A375P, A375M, A375SM cell lines. HUVEC adhesion and reorganization on A375 conditioned matrix was tenascin-dependent and could be inhibited with antibodies against human tenascin. HUVEC adhesion to A375SM-conditioned matrix and tenascin require alpha(v)beta(3) while reorganization may require alpha2beta1 as well. Our results suggest that tenascin plays a role in integrin-dependent adhesion and reorganization of HUVECs in response to the extracellular matrix of metastatic melanoma cells. PMID- 22323894 TI - Allylic Amines as Key Building Blocks in the Synthesis of (E)-Alkene Peptide Isosteres. AB - Nucleophilic imine additions with vinyl organometallics have developed into efficient, high yielding, and robust methodologies to generate structurally diverse allylic amines. We have used the hydrozirconation-transmetalation-imine addition protocol in the synthesis of allylic amine intermediates for peptide bond isosteres, phosphatase inhibitors, and mitochondria-targeted peptide mimetics. The gramicidin S-derived XJB-5-131 and JP4-039 and their analogs have been prepared on up to 160 g scale for preclinical studies. These (E)-alkene peptide isosteres adopt type II' beta-turn secondary structures and display impressive biological properties, including selective reactions with reactive oxygen species (ROS) and prevention of apoptosis. PMID- 22323895 TI - Niacin extended-release/simvastatin combination therapy produces larger favorable changes in high-density lipoprotein particles than atorvastatin monotherapy. AB - BACKGROUND: The purpose of this research was to compare the effects of niacin extended-release in combination with simvastatin (NER/S) versus atorvastatin monotherapy on high-density lipoprotein (HDL) particle number and size in patients with hyperlipidemia or dyslipidemia from the SUPREME study. METHODS: This was a post hoc analysis of patients (n = 137) who completed the SUPREME study and who had lipid particle number and size measurements at both baseline and at week 12 by nuclear magnetic resonance spectroscopy. Following >=4 weeks without lipid-modifying therapy (washout period), the patients received NER/S 1000/40 mg/day for 4 weeks followed by NER/S 2000/40 mg/day for 8 weeks, or atorvastatin 40 mg/day for 12 weeks. Median percent changes in HDL particle number and size from baseline to week 12 were compared between the NER/S and atorvastatin treatment groups using the Wilcoxon rank-sum test. Distribution of HDL particle subclasses at week 12 was compared between the treatment groups using the Cochran-Mantel-Haenszel test. RESULTS: Treatment with NER/S resulted in a significantly greater percent reduction in small HDL particle number at week 12 compared with atorvastatin monotherapy (-1.8% versus 4.2%, P = 0.014), and a numerically greater percent increase in large HDL particle number (102.4% versus 39.2%, P = 0.078) compared with atorvastatin monotherapy. A significantly greater percent increase in HDL particle size from baseline at week 12 was observed with NER/S compared with atorvastatin (6.0% versus 1.3%, P < 0.001). NER/S treatment also resulted in a significant shift in HDL particle size from small and medium at baseline to large at week 12 (P < 0.0001). CONCLUSION: Treatment with NER/S resulted in larger favorable changes in number and size of HDL particle subclasses compared with atorvastatin monotherapy, including a numerically greater increase in number of large HDL particles, and a significantly greater decrease in number of small HDL particles compared with atorvastatin monotherapy. In addition, NER/S treatment resulted in a significant change in HDL particle size distribution from small and medium to large. PMID- 22323896 TI - New oral antithrombotics: focus on dabigatran, an oral, reversible direct thrombin inhibitor for the prevention and treatment of venous and arterial thromboembolic disorders. AB - Venous thromboembolism, presenting as deep vein thrombosis or pulmonary embolism, is a major challenge for health care systems. It is the third most common vascular disease after coronary heart disease and stroke, and many hospitalized patients have at least one risk factor. In particular, patients undergoing hip or knee replacement are at risk, with an incidence of asymptomatic deep vein thrombosis of 40%-60% without thromboprophylaxis. Venous thromboembolism is associated with significant mortality and morbidity, with patients being at risk of recurrence, post-thrombotic syndrome, and chronic thromboembolic pulmonary hypertension. Arterial thromboembolism is even more frequent, and atrial fibrillation, the most common embolic source (cardiac arrhythmia), is associated with a five-fold increase in the risk of stroke. Strokes due to atrial fibrillation tend to be more severe and disabling and are more often fatal than strokes due to other causes. Currently, recommended management of both venous and arterial thromboembolism involves the use of anticoagulants such as coumarin and heparin derivatives. These agents are effective, although have characteristics that prevent them from providing optimal anticoagulation and convenience. Hence, new improved oral anticoagulants are being investigated. Dabigatran is a reversible, direct thrombin inhibitor, which is administered as dabigatran etexilate, the oral prodrug. Because it is the first new oral anticoagulant that has been licensed in many countries worldwide for thromboprophylaxis following orthopedic surgery and for stroke prevention in patients with atrial fibrillation, this compound will be the main focus of this review. Dabigatran has been investigated for the treatment of established venous thromboembolism and prevention of recurrence in patients undergoing hip or knee replacement, as well as for stroke prevention in atrial fibrillation patients with a moderate and high risk of stroke. PMID- 22323898 TI - Penalized classification using Fisher's linear discriminant. AB - We consider the supervised classification setting, in which the data consist of p features measured on n observations, each of which belongs to one of K classes. Linear discriminant analysis (LDA) is a classical method for this problem. However, in the high-dimensional setting where p ? n, LDA is not appropriate for two reasons. First, the standard estimate for the within-class covariance matrix is singular, and so the usual discriminant rule cannot be applied. Second, when p is large, it is difficult to interpret the classification rule obtained from LDA, since it involves all p features. We propose penalized LDA, a general approach for penalizing the discriminant vectors in Fisher's discriminant problem in a way that leads to greater interpretability. The discriminant problem is not convex, so we use a minorization-maximization approach in order to efficiently optimize it when convex penalties are applied to the discriminant vectors. In particular, we consider the use of L(1) and fused lasso penalties. Our proposal is equivalent to recasting Fisher's discriminant problem as a biconvex problem. We evaluate the performances of the resulting methods on a simulation study, and on three gene expression data sets. We also survey past methods for extending LDA to the high dimensional setting, and explore their relationships with our proposal. PMID- 22323897 TI - Tackling sleeplessness: psychological treatment options for insomnia in older adults. AB - This paper provides a broad review of the extant literature involving the treatment of sleeplessness in older adults with insomnia. First, background information (including information regarding key issues in late-life insomnia and epidemiology of late-life insomnia) pertinent to achieving a general understanding of insomnia in the elderly is presented. Next, theories of insomnia in older adults are examined and discussed in relation to treatment of insomnia in late-life. With a general knowledge base provided, empirical evidence for both pharmacological (briefly) and psychological treatment options for insomnia in late-life are summarized. Recent advances in the psychological treatment of insomnia are provided and future directions are suggested. This review is not meant to be all-inclusive; however, it is meant to provide professionals across multiple disciplines (physicians; psychologists; applied and basic researchers) with a mix of breadth and depth of knowledge related to insomnia in late-life. It is our hope that readers will see the evidence in support of psychological treatments for late-life insomnia, and the utility in continuing to investigate this treatment modality. PMID- 22323899 TI - Epicardial Ablation on the Beating Heart: Limited Efficacy of a Novel, Cooled Radiofrequency Ablation Device. AB - OBJECTIVE: To perform a minimally invasive procedure for atrial fibrillation without cardiopulmonary bypass, it is necessary to create transmural lesions on the beating heart. Although bipolar radiofrequency clamps can isolate the pulmonary veins, they have difficulty in performing any other left atrial lesions, particularly those of the traditional Cox-Maze procedure. This study examined the performance of an internally cooled, bipolar radiofrequency device designed for such an application. METHODS: Eleven domestic pigs underwent median sternotomy. Five animals had eight atrial lesions created with the radiofrequency device at times of 20, 30, 40, and 50 seconds. In six other pigs, the device was compared with another technology that has been used clinically for epicardial, beating heart ablation, the Guidant Flex 4 microwave device. The tissue was stained with 2,3,5-triphenyl-tetrazoluim chloride, and the lesions were sectioned at 5-mm intervals. Lesion width, depth, and transmurality were evaluated. RESULTS: The radiofrequency device had a linear dose-response relationship. Lesions were wider and deeper with increasing ablation times. A total of 40%, 45%, 60%, and 67% of lesions were transmural at times of 20, 30, 40, and 50 seconds, respectively. Ninety-one percent of lesions in tissue up to 4-mm thick were transmural after 50 seconds. However, performance in thicker tissue was poor. Lesions created by the device were deeper and more likely to be transmural than the Flex 4. CONCLUSIONS: This internally cooled, bipolar radiofrequency device can reliably create transmural lesions on tissue up to 4-mm thick and performs better than a microwave device. PMID- 22323900 TI - Differing processing abilities for specific face properties in mid-childhood and adulthood. AB - The ability to process facial information is vital for social interactions. Previous research has shown that mature face processing depends on the extraction of featural and configural face information. It has been also shown that the acquisition of these processing skills is prolonged in children. The order in which different face properties are processed is currently less understood. Namely, while some research has supported a parallel-route model which groups different properties according to their variability, other studies have shown that specific invariant properties, such as facial identity, can serve as a reference frame for interpreting more dynamic aspects, such as facial expression or eye gaze direction. The current study tested a different approach, which proposes that face property processing varies with task requirements. Sixteen adults did a same-different task where the second face could differ from the first in the identity, expression, or gaze, or any combination of those. We found that reaction times increased and accuracy rates decreased when the identity was repeated, suggesting that changes in facial identity were the most salient ones. Finally, we tested two groups of 7-to 8- and 10- to 11-year-old children and found lower accuracy rates for those face properties that rely in particular on configural information processing strategies. This suggests that while overall, face processing strategies are adult-like from 7 years of age, the processing of specific face properties develops continuously throughout mid-childhood. PMID- 22323901 TI - Polymorphism in apoA1 Influences High-Density Lipoprotein Cholesterol Levels but Is Not a Major Risk Factor of Alzheimer's Disease. AB - BACKGROUND: Apolipoprotein A1 (apoA1) is the major apolipoprotein constituent of the high-density lipoprotein (HDL) and is involved in reverse cholesterol transport. Variation in the apoA1 gene might influence the function of the protein and, thus, brain cholesterol metabolism, leading to an increased risk for Alzheimer's disease (AD). AIM: In the current report, we investigated the role of the functional apoA1 polymorphism (-75 G/A) as a genetic risk factor for AD in a Tunisian population. METHODS: 173 AD patients and 150 healthy controls were studied. RESULTS: No association was found between this genetic variation in apoA1 gene and the risk of AD. The presence of the (-75 G/A) A allele appeared, however, to be associated with lower levels of cerebrospinal fluid Abeta42 and HDL cholesterol levels in sera. CONCLUSION: Our data support the observation that apoA1 polymorphism influences cholesterol metabolism and Abeta42 deposition in the brain. PMID- 22323902 TI - Lack of Association between Apolipoprotein E Polymorphism with Age at Onset of Subcortical Vascular Dementia. AB - BACKGROUND AND PURPOSE: The relationship between apolipoprotein E (ApoE) and onset of vascular dementia remains controversial. The aim of this study was to evaluate the relationship between ApoE polymorphism and the onset of subcortical vascular dementia (SVaD) compared to Alzheimer's disease (AD) and normal controls. METHODS: The study was comprised of 61 patients with SVaD (42 Binswanger type, 19 lacunar type) and 112 patients with AD (16 early-onset AD, 96 late-onset AD) as well as 284 age-, gender- and education-matched normal controls. The diagnosis of SVaD was based on modified NINDS-AIREN criteria, and the diagnosis of AD was based on NINCDS-ADRDA criteria. ApoE polymorphism was genotyped in all participants. RESULTS: None of the three ApoE alleles was more prevalent in SVaD patients compared to normal controls, which was the case when both Binswanger and lacunar types were analyzed separately. ApoE ?4 did not accelerate the onset of SVaD (OR 1.66, 95% CI: 0.8-3.4), in contrast to a significant relation with late-onset AD (OR 3.78, 95% CI: 2.2-6.5). CONCLUSION: Our results suggest that ApoE polymorphism is not associated with the onset of SVaD and that the two subtypes of SVaD may share similar pathophysiologies. PMID- 22323903 TI - Regionalization of pediatric emergency care in Korea. AB - In order to care for an ill or injured child, it is crucial that every emergency department (ED) has a minimum set of personnel and resources because the majority of children are brought to the geographically nearest ED. In addition to adequate preparation for basic pediatric emergency care, a comprehensive, specialized healthcare system should be in place for a critically-ill or injured victim. Regionalization of healthcare means a system providing high-quality and cost effective care for victims who present with alow frequency, but critical condition, such as multiple trauma or cardiac arrest. Within the pediatric field, neonatal intensive care and pediatric trauma care are good examples of regionalization. For successful regionalized pediatric emergency care, all aspects of a pediatric emergency system, from pre-hospital field to hospital care, should be categorized and coordinated. Efforts to set up the pediatric emergency care regionalization program based on a nationwide healthcare system are urgently needed in Korea. PMID- 22323904 TI - Regionalization of neonatal intensive care in Korea. AB - In the current era of low-birth rate in Korea, it is important to improve our neonatal intensive care and to establish an integrative system including a regional care network adequate for both high-risk pregnancies and high-risk newborn infants. Therefore, official discussion for nation-wide augmentation, proper leveling, networking, and regionalization of neonatal and perinatal care is urgently needed. In this report, I describe the status of neonatal intensive care in Korea, as well as nationwide flow of transfer of high-risk newborn infants and pregnant women, and present a short review of the regionalization of neonatal and perinatal care in the Unites States and Japan. It is necessary not only to increase the number of neonatal intensive care unit (NICU) beds, medical resources and manpower, but also to create a strong network system with appropriate leveling of NICUs and regionalization. A systematic approach toward perinatal care, that includes both high-risk pregnancies and newborns with continuous support from the government, is also needed, which can be spearheaded through the establishment of an integrative advisory board to propel systematic care forward. PMID- 22323905 TI - Infectious diseases in children and adolescents in the Republic of Korea; Past & recent status. AB - Compared to the past decades, in recent decades, environmental and hygienic conditions in the Republic of Korea have improved along with socioeconomic developments, and the incidence of most infectious diseases, especially vaccine preventable diseases, has greatly decreased due to active immunization with the developed level of health care. However, the incidence of some diseases has been increasing, and new diseases have been emerging. To cope with such changes actively, the government put the "Law for Control and Prevention of Infectious Diseases" into effect; this law was entirely revised on December 30, 2010. In this report, I review the past and recent status of infectious diseases in the Republic of Korea, following the introduction of this law, on the basis of data in the "National Notifiable Disease Surveillance System", which had been accumulated between the years 1960 and 2010. PMID- 22323906 TI - Comparison of air pollution and the prevalence of allergy-related diseases in Incheon and Jeju City. AB - PURPOSE: A high level of air pollutants can increase the number of patients with allergy-related diseases such as asthma and allergic rhinitis (AR). To analyze the association between air pollution and allergic disease, we investigated 2 areas in Korea: Incheon, an industrial area, and Jeju, a non-industrialized area. METHODS: Second grade students at elementary schools (11 schools in Incheon and 45 schools in Jeju) were examined in a cross-sectional study. A questionnaire was used and a skin prick test was performed. The levels of NO(2), CO(2), O(3), particulate matter (PM) PM(10/2.5), formaldehyde, tVOCs, and dust mites in the classrooms and grounds were determined. RESULTS: The levels of outdoor CO, PM(10), and PM(2.5) were significantly higher in Incheon (P<0.01). The levels of indoor CO, CO(2), PM(10), PM(2.5) were significantly higher in Incheon (P<0.01). The prevalence rates of AR symptoms at any time, AR symptoms during the last 12 months, diagnosis of rhinitis at any time, and AR treatment during the last 12 months were significantly higher in Incheon (P<0.01). The prevalence rate of wheezing or whistling at any time, and wheezing during the last 12 months were significantly higher in Incheon (P<0.01). CONCLUSION: We found that the children living in Incheon, which was more polluted than Jeju, had a higher rate of AR and asthma symptoms compared to children in Jeju. To determine the effect of air pollution on the development of the AR and asthma, further studies are needed. PMID- 22323907 TI - Wolff-Parkinson-White syndrome in young people, from childhood to young adulthood: relationships between age and clinical and electrophysiological findings. AB - PURPOSE: The aim of the present study was to evaluate the characteristics of electrophysiologic studies (EPS) and radiofrequency ablation (RFA) performed in subjects aged less than 30 years with Wolff-Parkinson-White (WPW) syndrome, particularly pediatric patients under 18 years of age, based on our experience. METHODS: Two hundred and one consecutive patients with WPW syndrome were recruited and divided to 3 groups according to age: group 1, 6 to 17 years; group 2, 18 to 29 years; and group 3, 30 to 60 years. The clinical, electrophysiological, and therapeutic data for these patients were evaluated by a retrospective medical record review. RESULTS: A total of 73 (36%) of these patients were <30 years of age. Although there were more males than females in group 2 (male:female, 31:11), there was no sex difference in group 1 (male:female, 16:15). Left accessory pathway was detected less frequently in group 1 (32%, 10/31) than in group 2 (57%, 24/42) and group 3 (63%, 81/128) (P=0.023 and P=0.002, respectively). CONCLUSION: The present study describes several different electrophysiological characteristics in children and adolescents with WPW syndrome. Therefore, when EPS and RFA are performed in children and adolescence with WPW syndrome, we recommend that these characteristics be considered. PMID- 22323908 TI - Early congenital syphilis presenting with skin eruption alone: a case report. AB - Congenital syphilis is one of the most well-known congenital infections, yet it remains a worldwide public health problem. Congenital syphilis can involve any organ system and present with various symptoms. However, early diagnosis of congenital syphilis is difficult because more than half of the affected infants are asymptomatic, and the signs in symptomatic infants may be subtle and nonspecific. Here, we report a case of congenital syphilis with only a skin rash, which led to a delay in diagnosis. This case indicates that congenital syphilis should be considered throughout early childhood. PMID- 22323909 TI - A case of idiopathic isolated hypoglossal nerve palsy in a Korean child. AB - Hypoglossal nerve palsy (HNP) is an uncommon neurological abnormality that can provoke characteristic clinical signs, including unilateral atrophy of the tongue musculature. We present the case of a healthy 11-year-old Korean male who was admitted to the outpatient department of our institution with acute onset dysarthria, tongue fasciculations, and right-sided tongue weakness upon awakening. His evaluation included a virology work-up, neck magnetic resonance imaging (MRI), brain MRI, and otorhinolaryngological physical examination; all tests were normal and showed no evidence of inflammation. Fifteen days after the onset of symptoms, the patient recovered completely. Herein, we report a case of idiopathic isolated HNP in a Korean male. PMID- 22323910 TI - Oncoplastic surgical techniques for personalized breast conserving surgery in breast cancer patient with small to moderate sized breast. AB - Oncoplastic surgery has revolutionized the field of breast conserving surgery (BCS). The final aims of this technique are to obtain an adequate resection margin that will reduce the rate of local recurrence while simultaneously improving cosmetic outcomes. To obtain successful results after oncoplastic surgery, it is imperative that patients be risk-stratified based on risk factors associated with positive margins, that relevant imaging studies be reviewed, and that the confirmation of negative margins be confirmed during the initial operation. Patients who had small- to moderate-sized breasts are the most likely to be dissatisfied with the cosmetic outcome of surgery, even if the defect is small; therefore, oncoplastic surgery in this population is warranted. Reconstruction of the remaining breast tissue is divided into volume displacement and volume replacement techniques. The use of the various oncoplastic surgeries is based on tumor location and excised breast volume. If the excised volume is less than 100 g, the tumor location is used to determine which technique should be used, with the most commonly used technique being volume displacement. However, if the excised volume is greater than 100 g, the volume replacement method is generally used, and in cases where more than 150 g is excised, the latissimus dorsi myocutaneous flap may be used to obtain a pleasing cosmetic result. The local recurrence rate after oncoplastic surgery was lower than that of conventional BCS, as oncoplastic surgery reduced the rate of positive resection margins by resecting a wider section of glandular tissue. If the surgeon understands the advantages and disadvantages of oncoplastic surgery, and the multidisciplinary breast team is able to successfully collaborate, then the success rate of BCS with partial breast reconstruction can be increased while also yielding a cosmetically appealing outcome. PMID- 22323911 TI - Clinical significance of annexin A1 expression in breast cancer. AB - PURPOSE: The expression of Annexin A1 (ANXA1) is known to be reduced in human breast cancer; however, the role of ANXA1 expression in the development of breast cancer remains unclear. In this study, we determined the relationship between the expression features of ANXA1 and the prognostic factors of breast cancer. METHODS: Human breast tissues were obtained from patients specimens who had undergone breast surgery or core needle biopsies. The patterns of ANXA1 expression were analyzed by immunohistochemical staining in relation to histopathological diagnosis, clinical characteristics and outcomes. RESULTS: One hundred eighty-two cases were included and the mean age of the patients was 46.34 +/- 11.5 years. A significant loss of ANXA1 expression was noted in both ductal carcinoma in situ (DCIS) and invasive carcinomas compared to normal breast tissues (p<0.001) and benign breast diseases (p<0.001). There was a significant alteration in ANXA1 expression according to hormone receptor status (p<0.001), cancer intrinsic type (p<0.001), and nuclear grade (p=0.004) in invasive cancer. In a univariate analysis, ANXA1 positivity tended to be related with poor breast cancer-related survival (p=0.062); however, the same results was not realized in multivariate results (p=0.406). HER2 overexpression and TNM staging were significantly associated with relapse-free survivals (RFS) in the multivariate analysis (p=0.037, p=0.048, respectively). In particular, in node-positive patients (p=0.048), HER2 overexpressed patients (p=0.013), and non-triple negative breast cancer patients (p=0.002), ANXA1 overexpression was correlated with poor RFS. CONCLUSION: Although significant loss of ANXA1 expression was noted in breast cancer including DCIS and invasive carcinoma, in cases of invasive cancer, overexpression of ANXA1 was related to unfavorable prognostic factors. And these results imply that ANXA1 plays dualistic roles and is involved in variable mechanisms related to cancer development and progression. PMID- 22323912 TI - Prognostic Implications of MicroRNA-21 Overexpression in Invasive Ductal Carcinomas of the Breast. AB - PURPOSE: Among more than 500 microRNAs, microRNA-21 (miR-21) is known to act as an oncogene. The aim of this study was to investigate the significance of miR-21 expression level in relation with clinicopathological factors and prognosis in breast cancer. METHODS: MicroRNA was extracted from cancer and normal breast tissue of 109 breast cancer patients who underwent surgery from 2002 to 2004 using the Taqman(r) MicroRNA Assay. The correlation between miR-21 expression and clinicopathologic features was analyzed and the significance of miR-21 as a prognostic factor and its relationship with survival was determined. RESULTS: MiR 21 expression was higher in cancer tissues than in normal tissues (p<0.0001). High miR-21 expression was associated with mastectomy, larger tumor size, higher stage, higher grade, estrogen receptor (ER) negative, human epidermal growth factor receptor 2 (HER2) positive, HER2 positive breast cancer subtype, high Ki 67 expression, and death. On multivariate analysis, prognostic factors for overall survival were ER and miR-21. High miR-21 expression was significantly related to lower overall survival (p=0.031). CONCLUSION: This study supports the role of miR-21 as an oncogene and a biomarker for breast cancer with its high expression in cancer tissues and its relationship with other prognostic factors and survival. PMID- 22323913 TI - Silver-Enhanced In Situ Hybridization as an Alternative to Fluorescence In Situ Hybridization for Assaying HER2 Amplification in Clinical Breast Cancer. AB - PURPOSE: Valid determination of HER2 status is a prerequisite to establish an adequate treatment strategy for breast cancer patients, regardless of the disease stage. The goal of this study was to examine the feasibility of the newly developed silver-enhanced in situ hybridization (SISH) technique as an alternative to fluorescence in situ hybridization (FISH) for HER2 assay in primary invasive breast cancer. METHODS: FISH and SISH for HER2 amplification were performed using tissue microarray. Both methods were used in 257 consecutive primary breast cancers. RESULTS: HER2 amplification was observed in 62 (23.1%) of a total of 257 breast cancers based on SISH. Of the 257 breast cancers measured using both methods, the results of the two methods were consistent in 248 (concordance, 96.5%; kappa=0.903). When we compared HER2 amplification in the primary tumor with the metastatic lymph nodes of the same patients, HER2 amplification was observed in nine cases (14.0%) out of 64 cases in which HER2 was not amplified in the primary tumors. In contrast, HER2 status was completely preserved in metastatic lymph nodes showing HER2 amplification in the primary tumor. CONCLUSION: These results indicate that SISH can be a feasible alternative to FISH in the clinical setting. In node-positive breast cancer, confirmation of the HER2 status of the metastatic lymph nodes appears to be mandatory, regardless of the HER2 status of the primary tumors. PMID- 22323914 TI - Chemotherapy response assay test and prognosis for breast cancer patients who have undergone anthracycline- and taxane-based chemotherapy. AB - PURPOSE: A chemotherapy response assay test is performed to evaluate the degree of tumor growth inhibition by a chemotherapeutic agent. Several studies have been done on its usefulness; however, to the best of our knowledge, only a few studies concerning the relationship between chemotherapy response assay test results and breast cancer patients' prognoses have been conducted. Thus, we performed this study to analyze this relationship. METHODS: Among breast cancer patients who underwent curative surgery and neoadjuvant or adjuvant chemotherapy between August 2004 and December 2009, 102 were enrolled in this study. Chemotherapeutic regimens for patients were doxorubicin plus taxane or doxorubicin plus cyclophosphamide followed by taxane. We divided these patients into two groups (sensitive group [n=19] and resistant group [n=83]) and analyzed the relationship between chemosensitivity results and patient prognosis. RESULTS: The sensitive group was associated with poor disease-free survival (DFS) (p=0.003) and overall survival (OS) (p<0.001). No significant differences were observed in tumor histology (p=0.548), tumor size (p=0.479), number of metastatic lymph nodes (p=0.326), histologic grade (p=0.077), or nuclear grade (p=0.216) between the two groups. However, in respect to molecular subtype, the HER2-positive type and triple negative breast cancer were more frequently observed in the sensitive group (p=0.001). In a univariate and multivariate analysis for DFS, doxorubicin sensitivity was significantly associated with a poor prognosis (p<0.05). CONCLUSION: Better chemosensitivity results are associated with a poor prognosis in breast cancer patients who have undergone anthracycline- and taxane-based chemotherapy, however, examination of additional cases and the use of a longer study period are needed. PMID- 22323915 TI - Locoregional recurrence of breast conserving surgery after preoperative chemotherapy in korean women with locally advanced breast cancer. AB - PURPOSE: Preoperative chemotherapy has been used to increase the rate of breast conserving surgery (BCS) in Caucasian women. However, whether it would also increase the rate of BCS in Korean women has not been verified. The aim of this study was to determine the effectiveness of preoperative chemotherapy to make BCS possible in Korean women who have locally advanced cancer without any increase of locoregional recurrence according to operation methods (BCS vs. mastectomy). METHODS: From August 2002 to April 2005, 205 patients with stage II or III breast cancer were enrolled in a phase III randomized trial of preoperative chemotherapy. Surgeons decided on the type of surgery (mastectomy or BCS) at initial diagnosis. By randomization, patients received four cycles of either docetaxel/capecitabine or doxorubicin/cyclophosphamide followed by surgery and crossover to the other treatment as postoperative chemotherapy. RESULTS: The mean tumor size was 3.29 cm and the mean breast volume was 489 cc at diagnosis. After preoperative chemotherapy, clinical response was shown in 76.0% of the patients. Of the 71 patients planned for a mastectomy at initial diagnosis, 27 patients underwent BCS (38.0%). Clinical T stage after preoperative chemotherapy, pathologic T size and lymphatic invasion were correlated with conversion to BCS. In multivariate analysis, only lymphatic invasion showed statistical significance. Locoregional disease-free survival did not statistically differ between the two operation methods for the patients who were planned for a mastectomy at the initial exam. CONCLUSION: This study showed that preoperative chemotherapy also increased the rate of BCS, while avoiding any increase of locoregional recurrence in Korean women with locally advanced breast cancer. PMID- 22323916 TI - How many sentinel lymph nodes are enough for accurate axillary staging in t1-2 breast cancer? AB - PURPOSE: During a sentinel lymph node biopsy (SLNB) for breast cancer, the appropriate number of sentinel lymph nodes (SLNs) to be removed for accurate axillary staging is still controversial. We hypothesized that there might be an optimal threshold number of SLNs. We investigated how many SLNs should be removed to achieve an acceptable accuracy and ensure minimal morbidity. METHODS: We reviewed data of 328 patients with invasive breast cancer who underwent SLNB followed by complete level I and II axillary dissection between January 2004 and December 2005. The false negative rate (FNR) and accuracy of SLNB according to the number of removed SLNs were evaluated. RESULTS: The mean number of SLNs removed was 3.0 (range, 1-14), and that of total retrieved axillary lymph nodes was 17.5 (range, 10-40). In total, 111 (33.8%) patients had positive nodes on the permanent pathological report. Among them, 12 patients had negative SLNs; thus, the overall FNR of SLNB was 10.8% (12/111) and the accuracy was 96.3% (316/328). The FNR was 26.6% for a single SLN, 8.0% for two, and 11.1% for three. In cases where four or more SLNs were removed, the FNR decreased to 0% and accuracy reached 100%. CONCLUSION: Our data suggest that a SLNB should not only remove one or two of the hottest node(s) when other hot nodes exist. We also suggest that four might be an optimal threshold number of SLNs to be removed and that removal of more than four SLNs does not improve axillary staging accuracy. PMID- 22323917 TI - Ductal carcinoma in situ and sentinel lymph node biopsy. AB - PURPOSE: Axillary lymph node status is the strongest prognostic indicator of survival for women with breast cancer. The purpose of this study was to evaluate whether sentinel lymph node biopsy (SLNB) is required in patients with an initial diagnosis of ductal carcinoma in situ (DCIS). METHODS: A retrospective analysis was performed of 78 patients with an initial diagnosis of DCIS between December 2002 and April 2010 and who proceeded to have either SLNB or axillary node dissection performed as part of their primary surgical procedure. The study focused on the rates of axillary node metastasis and the underestimation of invasive carcinoma at an initial diagnosis. RESULTS: Forty-eight patients underwent SLNB and 18 patients underwent axillary node dissection. Only 1 of 66 patients (1.5%) had a positive sentinel lymph node. After definite surgery, the final diagnosis was changed to invasive ductal carcinoma (IDC) in 12 patients and DCIS with microinvasion in 2 patients; 14 of 78 patients (17.9%) were therefore underestimated at preoperative histological examinations. In 35 patients who were diagnosed DCIS by core needle biopsy (CNB), 13 patients (37.1%) were upstaged into IDC or DCIS with microinvasion in the final diagnosis. The statistically significant factors predictive of invasive breast cancer were a large tumor size and HER2 overexpression. CONCLUSION: The rates of SLNB positivity in pure DCIS are very low, and there is continuing uncertainty about its clinical importance. However in view of the high rate of underestimation of invasive carcinoma in patients with an initial diagnosis of DCIS, SLNB appears to be appropriate in these patients, especially in the case when DCIS is diagnosed by a core needle biopsy. In patients with an initial diagnosis of DCIS by CNB, SLNB should be considered as part of the primary surgical procedure, when preoperative variables show a tumor larger than 2.35 cm and with HER2 overexpression. PMID- 22323918 TI - Mucinous carcinoma of the breast in comparison with invasive ductal carcinoma: clinicopathologic characteristics and prognosis. AB - PURPOSE: Mucinous carcinoma (MC) of the breast is a rare histologic type of mammary neoplasm. The objective of this study was to evaluate the long-term disease-free survival (DFS) and overall survival (OS) of MC. METHODS: We conducted a retrospective analysis of all MC cases reported to a database between 1994 and 2010. Clinicopathological characteristics and survival of 268 MC cases were reviewed and compared with 2,455 invasive ductal carcinoma-not otherwise specified (IDC-NOS) cases. RESULTS: The MC cases were of a younger age, involved less lymph nodes, lower stage, more expression of hormonal receptors, and less HER2 overexpression compared to the IDC-NOS cases. The 5-year DFS rate for MC was 95.2% compared to 92.0% for IDC-NOS. The 5-year OS rate for MC was 98.9% compared to 94.9% for IDC-NOS. Multivariate analysis using Cox regression revealed that the mucinous type was a significant prognostic factor for DFS with lower nodal status (N stage) and hormonal therapy. For OS, only N stage was the most significant prognostic factor followed by adjuvant chemotherapy and adjuvant hormonal therapy. CONCLUSION: MC was shown to be associated with a better DFS than IDC-NOS, but it had a similar OS. Nodal status and adjuvant therapy appear to be more significant predictors of prognosis than histologic subtype. PMID- 22323919 TI - Clinical Significance of Age at the Time of Diagnosis among Young Breast Cancer Patients. AB - PURPOSE: The aims of this study were to investigate outcomes corresponding to age at diagnosis as categorized into 5-year intervals and to explore whether endocrine-responsive tumors display clinical benefits from endocrine therapy after chemotherapy among young breast cancer patients. METHODS: A total of 1,171 patients who were under 40 years old at diagnosis between 1985 and 2007 were divided into 3 subgroups: <=30 years (Group I, 13.3%), 31-35 years (Group II, 30.5%), and 36-40 years (Control group, 56.2%). Clinicopathological factors and outcomes were compared using a chi-square test, the Kaplan-Meier method, and Cox's hazards models. RESULTS: There were no significant differences in the characteristics and treatment patterns between the 3 groups, except for the grade, hormone receptors expression, and use of endocrine therap. Group I showed the worst survival and subsequently Group II presented worse outcomes than the Control group, mainly among hormone receptors-positive patients. Groups I and II showed increased risks of recurrence and death in multivariate analyses. Among 529 hormone receptors-positive patients who received chemotherapy, favorable outcomes for patients who were treated with endocrine agents were demonstrated, mainly in patients aged 35 years or less. However, interaction tests between the use of endocrine therapy and age at diagnosis were not significant. CONCLUSION: Age at diagnosis is an independent prognostic factor and the age of 35 years is a rational cut-off among young patients. Our subgroup analysis suggests that endocrine therapy may provide additional benefits even in young breast cancers. Therefore, further researches should be directed towards improving outcomes for this population. PMID- 22323920 TI - Does Immediate Breast Reconstruction after Mastectomy affect the Initiation of Adjuvant Chemotherapy? AB - PURPOSE: The frequency of immediate breast reconstruction (IBR) is increasing, and the types of reconstruction used are diverse. Adjuvant chemotherapy is a life saving intervention in selected high-risk breast cancer patients. The aim of our study was to determine how IBR and type of reconstruction affect the timing of the initiation of chemotherapy. METHODS: We obtained data from female breast cancer patients treated by mastectomy with IBR (IBR group) and without IBR (mastectomy only group) who received adjuvant chemotherapy between January 1, 2008, and December 31, 2010. We retrospectively collected data including patient characteristics, disease characteristics, treatment details, and treatment outcomes from our institutional electronic patient database and medical treatment records. The reconstruction types were categorized as deep inferior epigastric perforator (DIEP) flap, latissimus dorsi (LD) flap and tissue expander/implant (TEI). RESULTS: In total, 595 patients were included in this study. Of these patients, 43 underwent mastectomy with IBR (IBR group) and 552 patients did not undergo reconstruction (mastectomy only group). There was significant difference in the timing of the initiation of chemotherapy between the two groups (p<0.0001). There were no cases of delays of more than 12 weeks. In the IBR group, 20 patients received TEI, 9 patients were treated by the insertion DIEP flaps, and 14 patients were treated by LD flaps. There were no significant differences in the timing of chemotherapy according to the type of reconstruction (p=0.095). CONCLUSION: IBR delays the initiation of chemotherapy, but does not lead to omission or significant clinical delay in chemotherapy. Further, the type of reconstruction does not affect the timing of chemotherapy. PMID- 22323921 TI - Analysis of infections occurring in breast cancer patients after breast conserving surgery using mesh. AB - PURPOSE: Breast conserving surgery using mesh can effectively fill the defective space, but there is the risk of infection. METHODS: From June 2007 to August 2010, 243 patients who underwent breast conserving surgery with polyglactin 910 mesh insert for breast cancer at our institution were retrospectively studied. RESULTS: Infection occurred in 25 (10.3%) of 243 patients. When comparing the infection and non-infection groups in multivariate analysis, there was no significant difference in age, underlying disease, preoperative biopsy methods, mass location, axillary lymph node dissection, operative methods, neoadjuvant or adjuvant chemotherapy use, mass size and removed breast volume. The infection appeared more common only in patients with body mass index (BMI) greater than 25. Infection symptoms occurred, on average, 119.5 days after surgery, and the average duration of the required treatment was 34.4 days. Out of 25 patients with postoperative infection complications, 16 (64%) patients underwent incision and drainage with mesh removal, whereas the remaining 9 (36%) only required conservative treatment. CONCLUSION: During breast conserving surgery, the risk of infection is increased in patients with high BMI, and should be taken into account when considering insertion of a polyglactin 910 mesh. Patient's age, underlying disease and perioperative treatment methods were not significant risk factors for developing mesh infection. Given that most infections seem to develop symptoms one month after surgery, a long enough observation period should be initiated. Early detection and appropriate conservative treatments may effectively address infections, thus reducing the need for more invasive therapies. PMID- 22323922 TI - A rare case of male primary breast lymphoma. AB - Primary lymphoma of the breast is a rare occurrence because of the paucity of lymphoid tissue in the breast and is an even rarer entity in the male breast. Imaging, along with tissue diagnosis goes a long way in diagnosing breast lymphoma which has a significantly different management scheme than other breast neoplasms with respect to radio-chemotherapy rather than surgical resection. We present a case of primary male breast lymphoma which was evaluated with magnetic resonance imaging as well as other conventional imaging modalities and was treated by chemotherapy with a 7-month follow-up. PMID- 22323923 TI - Clinically Positive Axillary Lymphadenopathy May Lead to False Diagnosis of Overstaged Breast Cancer in Patients with Sjogren's Syndrome: A Case Report. AB - Sjogren's syndrome (SS) is an autoimmune disease that chronic inflammation and lymph node proliferation. Patients with SS carry a greater risk of developing lymphoproliferative malignancy. In addition to other organ cancers, breast cancer may also occur in these patients. Considering these, breast cancer in patients with SS can be misdiagnosed as being in an advanced stage particularly in the presence of axillary lymphadenopathy. Here, we report a rare case of a 45-year old woman with SS who presented with a breast mass. Radiology showed a 4 cm solid lesion and conglomerates of axillary lymphadonepathy. A breast biopsy revealed ductal carcinoma in situ. A modified radical mastectomy was performed; however, no axillary metastases were detected. Clinicians should remain vigilant to the possibility that a false clinical impression of axillary metastasis may occur in such patients with breast cancer. Therefore, axillary node status should be verified first. PMID- 22323924 TI - Acupuncture-related rapid dermal spread of breast cancer: a rare case. AB - Many ethnic Chinese patients seek second or adjuvant alternative therapies after breast cancer is diagnosed. Chinese herbs and acupuncture are the most popular methods in East Asia. We present a case of acupuncture manipulation-related cutaneous spread that no literature reported before. Post-acupuncture cutaneous spread was noted in a 54-year-old woman with left neck lymph node recurrence after complete surgery, chemotherapy and radiotherapy treatment. The results of chest computed tomography and skin biopsy showed the metastatic breast cancer in the dermis. Six courses of paclitaxel and gemcitabine followed by trastuzumab were given as therapeutic chemotherapy. The neck mass and cutaneous lesions subsided after 2 courses of chemotherapy. Direct puncture of a metastatic lymph node might increase the incidence of tumor spread on the skin. Therefore, despite the efficacy of complementary and alternative medicine, its safety and possible side effects should be more emphasized. PMID- 22323925 TI - Life-threatening acute hyponatremia with generalized seizure induced by low-dose cyclophosphamide in a patient with breast cancer. AB - Cyclophosphamide is commonly used in the treatment of malignant diseases. Symptomatic severe hyponatremia induced by low-dose cyclophosphamide is very uncommon worldwide. Recently we experienced a case of a 56-year-old woman with breast cancer who developed severe hyponatremia with generalized seizure after the first cycle of adjuvant chemotherapy with doxorubicin and cyclophosphamide. Her laboratory test showed a serum sodium of 116 mmol/L. Her hyponatremia was initially treated with hypertonic saline solution and furosemide. She completely recovered without neurological deficits after slow correction of the serum sodium concentration over two days. Clinicians must always keep in mind that life threatening acute hyponatremia can be induced by intravenous cyclophosphamide during chemotherapy, even if the dosage is low. PMID- 22323926 TI - Induction and function of type I and III interferon in response to viral infection. AB - The type I and III interferon (IFN) families consist of cytokines rapidly induced during viral infection that confer antiviral protection on target cells and are critical components of innate immune responses and the transition to effective adaptive immunity. The regulation of their expression involves an intricate and stringently regulated signaling cascade, initiated by recognition most often of viral nucleic acid in cytoplasmic and endosomal compartments and involving a series of protein conformational rearrangements and interactions regulated by helicase action, ubiquitin modification, and protein aggregation, culminating in kinase activation and phosphorylation of critical transcription factors and their regulators. The many IFN subtypes induced by viruses confer amplification, diversification, and cell-type specificity to the host response to infection, providing fertile ground for development of antiviral therapeutics and vaccines. PMID- 22323927 TI - Orthopaedic biofilm infections. AB - A recent paradigm shift in microbiology affects orthopaedic surgery and most other medical and dental disciplines because more than 65% of bacterial infections treated by clinicians in the developed world are now known to be caused by organisms growing in biofilms. These slime-enclosed communities of bacteria are inherently resistant to host defenses and to conventional antibacterial therapy, and these device-related and other chronic bacterial infections are unaffected by the vaccines and antibiotics that have virtually eliminated acute infections caused by planktonic (floating) bacteria. We examine the lessons that can be learned, within this biofilm paradigm, by the study of problems (e.g. non-culturability) shared by all biofilm infections and by the study of new therapeutic options aimed specifically at sessile bacteria in biofilms. Orthopaedic surgery has deduced some of the therapeutic strategies based on assiduous attention to patient outcomes, but much can still be learned by attention to modern research in related disciplines in medicine and dentistry. These perceptions will lead to practical improvements in the detection, management, and treatment of infections in orthopaedic surgery. PMID- 22323928 TI - President's address: 20 years of perspiration and 20 years of admiration. PMID- 22323929 TI - A job analysis of care helpers. AB - The aim of this study was to examine the roles of care helpers through job analysis. To do this, this study used the Developing A Curriculum Method (DACUM) to classify job content and a multi-dimensional study design was applied to identify roles and create a job description by looking into the appropriateness, significance, frequency, and difficulty of job content as identified through workshops and cross-sectional surveys conducted for appropriateness verification. A total of 418 care helpers working in nursing facilities and community senior service facilities across the country were surveyed. The collected data were analyzed using PASW 18.0 software. Six duties and 18 tasks were identified based on the job model. Most tasks were found to be "important task", scoring 4.0 points or above. Physical care duties, elimination care, position changing and movement assistance, feeding assistance, and safety care were identified as high frequency tasks. The most difficult tasks were emergency prevention, early detection, and speedy reporting. A summary of the job of care helpers is providing physical, emotional, housekeeping, and daily activity assistance to elderly patients with problems in independently undertaking daily activities due to physical or mental causes in long-term care facilities or at the client's home. The results of this study suggest a task-focused examination, optimizing the content of the current standard teaching materials authorized by the Ministry of Health and Welfare while supplementing some content which was identified as task elements but not included in the current teaching materials and fully reflecting the actual frequency and difficulty of tasks. PMID- 22323930 TI - Equity or equality in medical education. PMID- 22323931 TI - Self-financing students in private medical schools. PMID- 22323932 TI - Serial expression of hypoxia inducible factor-1alpha and neuronal apoptosis in hippocampus of rats with chronic ischemic brain. AB - OBJECTIVE: The purpose of this study is to investigate serial changes of hypoxia inducible factor 1alpha (HIF-1alpha), as a key regulator of hypoxic ischemia, and apoptosis of hippocampus induced by bilateral carotid arteries occlusion (BCAO) in rats. METHODS: Adult male Wistar rats were subjected to the permanent BCAO. The time points studied were 1, 2, 4, 8, and 12 weeks after occlusions, with n=6 animals subjected to BCAO, and n=2 to sham operation at each time point, and brains were fixed by intracardiac perfusion fixation with 4% neutral-buffered praraformaldehyde for brain section preparation. Immunohistochemistry (IHC), western blot and terminal uridine deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were performed to evaluate HIF-1alpha expression and apoptosis. RESULTS: In IHC and western blot, HIF-1alpha levels were found to reach the peak at the 2nd week in the hippocampus, while apoptotic neurons, in TUNEL assay, were maximal at the 4th week in the hippocampus, especially in the cornu ammonis 1 (CA1) region. HIF-1alpha levels and apoptosis were found to fluctuate during the time course. CONCLUSION: This study showed that BCAO induces acute ischemic responses for about 4 weeks then chronic ischemia in the hippocampus. These in vivo data are the first to show the temporal sequence of apoptosis and HIF-1alpha expression. PMID- 22323933 TI - A genome-wide study of moyamoya-type cerebrovascular disease in the korean population. AB - OBJECTIVE: Structural genetic variation, including copy-number variation (CNV), constitutes a substantial fraction of total genetic variability, and the importance of structural variants in modulating susceptibility is increasingly being recognized. CNV can change biological function and contribute to pathophysiological conditions of human disease. Its relationship with common, complex human disease in particular is not fully understood. Here, we searched the human genome to identify copy number variants that predispose to moya-moya type cerebrovascular disease. METHODS: We retrospectively analyzed patients who had unilateral or bilateral steno-occlusive lesions at the cerebral artery from March, 2007, to September, 2009. For the 20 subjects, including patients with moyamoya type pathologies and three normal healthy controls, we divided the subjects into 4 groups : typical moyamoya (n=6), unilateral moyamoya (n=9), progression unilateral to typical moyamoya (n=2) and non-moyamoya (n=3). Fragmented DNA was hybridized on Human610Quad v1.0 DNA analysis BeadChips (Illumina). Data analysis was performed with GenomeStudio v2009.1, Genotyping 1.1.9, cnvPartition_v2.3.4 software. Overall call rates were more than 99.8%. RESULTS: In total, 1258 CNVs were identified across the whole genome. The average number of CNV was 45.55 per subject (CNV region was 45.4). The gain/loss of CNV was 52/249, having 4.7 fold higher frequencies in loss calls. The total CNV size was 904,657,868, and average size was 993,038. The largest portion of CNVs (613 calls) were 1M-10M in length. Interestingly, significant association between unilateral moyamoya disease (MMD) and progression of unilateral to typical moyamoya was observed. CONCLUSION: Significant association between unilateral MMD and progression of unilateral to typical moyamoya was observed. The finding was confirmed again with clustering analysis. These data demonstrate that certain CNV associate with moyamoya-type cerebrovascular disease. PMID- 22323934 TI - Ischemic complications occurring in the contralateral hemisphere after surgical treatment of adults with moyamoya disease. AB - OBJECTIVE: Direct revascularization surgery is regarded as the most effective method of treatment of adults with moyamoya disease. These patients, however, have a higher risk of perioperative ischemic complications than do patients with atherosclerotic stroke, and are at risk for ischemic complications in the hemisphere contralateral to the one operated on. We investigated the incidence and risk factors for ischemic stroke in the contralateral hemisphere after surgical treatment of adults with moyamoya disease. METHODS: We retrospectively reviewed the medical records and results of neuroimaging studies on 79 hemispheres of 73 consecutive patients with adult moyamoya disease (mean+/-SD age, 37.96+/-11.27 years; range, 18-62 years) who underwent direct bypass surgery over 6 years. RESULTS: Ischemic complications occurred in 4 of 79 (5.1%) contralateral hemispheres, one with Suzuki stage 3 and three with Suzuki stage 4. Three patients showed posterior cerebral artery (PCA) involvement by moyamoya vessels. Advanced stage of moyamoya disease (Suzuki stages 4/5/6; p=0.001), PCA involvement (p=0.001) and postoperative hypotension (mean arterial blood pressure <80% of preoperative mean arterial blood pressure) on the first (p<0.0001) and second (p=0.003) days after surgery were significantly correlated with postoperative contralateral ischemic complications. CONCLUSION: In patients with advanced moyamoya disease and involvement of the PCA, intentional hypotension can result in ischemic stroke in the hemisphere contralateral to the one operated on. Careful control of perioperative blood pressure is crucial for good surgical results. PMID- 22323935 TI - Comparative Study of Brain Protection Effect between Thiopental and Etomidate Using Bispectral Index during Temporary Arterial Occlusion. AB - OBJECTIVE: This study was conducted to compare the effect of etomidate with that of thiopental on brain protection during temporary vessel occlusion, which was measured by burst suppression rate (BSR) with the Bispectral Index (BIS) monitor. METHODS: Temporary parent artery occlusion was performed in forty one patients during cerebral aneurysm surgery. They were randomly assigned to one of two groups. General anesthesia was induced and maintained with 1.5-2.5 vol% sevoflurane and 50% N(2)O. The pharmacological burst suppression (BS) was induced by a bolus injection of thiopental (5 mg/kg, group T) or etomidate (0.3 mg/kg, group E) according to randomization prior to surgery. After administration of drugs, the hemodynamic variables, the onset time of BS, the numerical values of BIS and BSR were recorded at every minutes. RESULTS: There were no significant differences of the demographics, the BIS numbers and the hemodynamic variables prior to injection of drugs. The durations of burst suppression in group E (11.1+/-6.8 min) were not statistically different from that of group T (11.1+/ 5.6 min) and nearly same pattern of burst suppression were shown in both groups. More phenylephrine was required to maintain normal blood pressure in the group T. CONCLUSION: Thiopental and etomidate have same duration and a similar magnitude of burst suppression with conventional doses during temporary arterial occlusion. These findings suggest that additional administration of either drug is needed to ensure the BS when the temporary occlusion time exceed more than 11 minutes. Etomidate can be a safer substitute for thiopental in aneurysm surgery. PMID- 22323936 TI - Clinical efficacy of radiation-sterilized allografts for sellar reconstruction after transsphenoidal surgery. AB - OBJECTIVE: The aim of this study was to assess the safety and efficacy of radiation-sterilized allografts of iliac bone and fascia lata from cadaver specimens to repair skull base defects after transsphenoidal surgery. METHODS: Between May 2009 and January 2010, 31 consecutive patients underwent endonasal transsphenoidal surgery and all patients received sellar reconstruction using allografts following tumor removal. The allografts were obtained from the local tissue bank and harvested from cadaver donors. The specimens used in our approach were tensor fascia lata and the flat area of iliac bone. For preparation, allografts were treated with gamma irradiation after routine screening by culture, and then stored at -70C. RESULTS: The mean follow-up period after surgery was 12.6 months (range, 7.4-16 months). Overall, postoperative cerebrospinal fluid (CSF) leaks occurred in three patients (9.7%) and postoperative meningitis in one patient (3.2%). There was no definitive evidence of wound infection at the routine postoperative follow-up examination or during re-do surgery in three patients. Postoperative meningitis in one patient was improved with the use of antibiotics and prolonged CSF diversion. CONCLUSION: We suggest that allograft materials can be a feasible alternative to autologous tissue grafts for sellar reconstruction following transsphenoidal surgery under selected circumstances such as no or little intraoperative CSF leaks. PMID- 22323937 TI - The effect of radiofrequency neurotomy of lower cervical medial branches on cervicogenic headache. AB - OBJECTIVE: Cervicogenic headache (CGH) is known to be mainly related with upper cervical problems. In this study, the effect of radiofrequency neurotomy (RFN) for lower cervical (C4-7) medial branches on CGH was evaluated. METHODS: Eleven patients with neck pain and headache, who were treated with lower cervical RFN due to supposed lower cervical zygapophysial joint pain without symptomatic intervertebral disc problem or stenosis, were enrolled in this study. CGH was diagnosed according to the diagnostic criteria of the cervicogenic headache international study group. Visual analogue scale (VAS) score and degree of VAS improvement (VASi) (%) were checked for evaluation of the effect of lower cervical RFN on CGH. RESULTS: The VAS score at 6 months after RFN was 2.7+/-1.3, which were significantly decreased comparing to the VAS score before RFN, 8.1+/ 1.1 (p<0.001). The VASi at 6 months after RFN was 63.8+/-17.1%. There was no serious complication. CONCLUSION: Our data suggest that lower cervical disorders can play a role in the genesis of headache in addition to the upper cervical disorders or independently. PMID- 22323938 TI - Acute-on-Chronic Subdural Hematoma: Not Uncommon Events. AB - OBJECTIVE: Patients with asymptomatic chronic subdural hematoma (SDH) are prone to fall or slip. Acute trauma on these patients may develop acute subdural bleeding over the chronic SDH. We recently experienced 9 patients with acute-on chronic SDH. We report the clinical and radiological features of this lesion. METHODS: We retrospectively examined the computed tomographic (CT) scans of 107 consecutive patients who diagnosed as chronic SDH from January 2008 to December 2010. All cases of CSDH were diagnosed on CT with or without MRI scan. RESULTS: Acute-on-chronic SDH is not rare, being 8% of chronic SDH. The most common cause of trauma was a slip in drunken state. Alcoholism with multiple episodes of trauma was one of the prominent histories. Acute-on-chronic SDH appeared as a hyperdense layer of clot with irregular blurred margin or lumps in liquefied hematoma. Single or two burr holes was usually effective to remove the hematoma. CONCLUSION: Repeated trauma may cause acute bleeding over the chronic SDH. It will be helpful to understand the role of repeated trauma as a mechanism of hematoma enlargement. PMID- 22323939 TI - Modified 'y-configured stents with waffle cone technique' for broad neck basilar top aneurysm. AB - Stent assisted coiling on intracranial broad neck aneurysm has been considered as an effective technique and has made the complex aneurysms amenable to coiling. However, stent navigation and application themselves often have the problems especially when the parent vessel angle (entrance between afferent and efferent vessel) is over 90 degrees. We report here a case of a ruptured broad neck basilar top aneurysm that was successfully coiled using two self-expandable stents (Enterprise and Neuroform) placed in a fashion of modified Y-configured stents with waffle cone technique. PMID- 22323940 TI - Emergent Endovascular Embolization for Iatrogenic Vertebral Artery Injury during Cervical Discectomy and Fusion. AB - Injury to the vertebral artery during anterior cervical discectomy is rare but potentially fatal. We report a case of cerebellar infarction after endovascular embolization for iatrogenic vertebral artery injury at C5-C6 during an anterior cervical discectomy and fusion. A 61-year-old man had an intraoperative injury of the right vertebral artery that occurred during anterior cervical discectomy and fusion at C5-C6. Hemorrhage was not controlled successfully by packing with surgical hemostatic agents. While the patient was still intubated, an emergency angiogram was performed. The patient underwent endovascular occlusion of the right V2 segment with coils. After the procedure, his course was uneventful and he did not show any neurologic deficits. Brain computed tomographic scans taken 3 days after the operation revealed a right cerebellar infarction. Anti-coagulation medication was administered, and at 3-month follow-up examination, he had no neurologic sequelae in spite of the cerebellar infarction. PMID- 22323941 TI - Computer-assisted modified mid-sacrectomy for en bloc resection of chordoma and preservation of bladder function. AB - A 67-year-old woman presented for evaluation of severe coccygeal pain. The computed tomography scans and magnetic resonance imaging showed an asymmetric midline sacral tumor invading the right lower portion of S2. To preserve both S2 nerve roots and to obtain negative surgical margins, a modified mid-sacrectomy with an aid of a computed navigation system was performed. The sacral tumor was excised en bloc with negative tumor margins. Both S2 nerve roots were preserved and additional reconstruction was not necessary because of minimal resection of the sacroiliac joint. We report a case of a sacral chordoma which was excised en bloc with adequate surgical margins by a computer-assisted modified mid sacrectomy. The computed navigation system may be a useful tool for tumor targeting and safe osteotomies in sacral tumor surgery via the posterior only approach. PMID- 22323942 TI - Vertical reduction using atlantoaxial facet spacer in basilar invagination with atlantoaxial instability. AB - Although posterior segmental fixation technique is becoming increasingly popular, surgical treatment of craniovertebral junctional disorders is still challenging because of its complex anatomy and surrounding critical neurovascular structures. Basilar invagination is major pathology of craniovertebral junction that has been a subject of clinical interest because of its various clinical presentations and difficulty of treatment. Most authors recommend a posterior occipitocervical fixation following transoral decompression or posterior decompression and occipitocervical fixation. However, both surgical modalities inadvertently sacrifice C0-1 and C1-2 joint motion. We report two cases of basilar invagination reduced by the vertical distraction between C1-2 facet joint. We reduced the C1-2 joint in an anatomical position and fused the joint with iliac bone graft and C1 2 segmental fixation using the polyaxial screws and rods C-1 lateral mass and the C-2 pedicle. PMID- 22323943 TI - An unusual case of cerebral penetrating injury by a driven bone fragment secondary to blunt head trauma. AB - Temple trauma that appears initially localized to the skin might possess intracranial complications. Early diagnosis and management of such complications are important, to avoid neurologic sequelae. Non-penetrating head injuries with intracranial hemorrhage caused by a driven bone fragment are extremely rare. A 53 year-old male was referred to our hospital because of intracerebral hemorrhage. He was a mechanic and one day before admission to a local clinic, tip of metallic rod hit his right temple while cutting the rod. Initial brain computed tomography (CT) and magnetic resonance imaging demonstrated scanty subdural hematoma at right temporal lobe and left falx and intracerebral hematoma at both frontal lobes. Facial CT with 3-D reconstruction images showed a small bony defect at the right sphenoid bone's greater wing and a small bone fragment at the left frontal lobe, crossing the falx. We present the unusual case of a temple trauma patient in whom a sphenoid bone fragment migrated from its origin upward, to the contralateral frontal lobe, producing hematoma along its trajectory. PMID- 22323944 TI - Moyamoya syndrome precipitated by cranial irradiation for craniopharyngioma in children. AB - Recently, combination of surgery and radiation therapy (RT) has been recommended in the treatment of craniopharyngioma. RT could be associated with late complications, including vasculopathy. We report two cases of the moyamoya syndrome seen in children with craniopharyngioma who received RT after surgical resection. Thirty-five patients in pediatric age with craniopharyngioma were surgically treated. Fifteen out of 35 patients underwent surgical resection followed by RT or gamma knife surgery. Two of the 15 were found to have symptoms of transient ischemic attack and were diagnosed as moyamoya syndrome through the cerebral angiography. Age at RT was 4 and 13 years, respectively. The latent period for development of the moyamoya syndrome was 27 months and 3 years, respectively, after RT. The RT dose of both patients was 54 Gy. These two patients received bilateral encephaloduroarteriosynangiosis procedures. We report here these two cases of radiation-induced moyamoya syndrome in pediatric craniopharyngioma. Pediatric patients with craniopharyngioma who received RT should be reminded, during follow-up, about the risk of development of the moyamoya syndrome. PMID- 22323945 TI - Modified trans-middle temporal gyrus approach for trigonal tumor to preserve visual field. AB - OBJECTIVE: We evaluated a modified trans-middle temporal gyrus (MTG) approach with good postoperative visual preservation for patients with trigonal tumors. METHODS: Three patients with a trigonal tumor were treated via the modified trans MTG approach guided by a neuro-navigator. Modified trans-MTG approach involve the incision at the MTG within 5 mm to the superior temporal sulcus. This approach makes a proper trajectory to the trigone but also reduces the retraction injury of MTG as little as possible to prevent postoperative visual field defect. Preoperative and postoperative visual field examination using perimetry was performed to evaluate the visual field. RESULTS: Three patients underwent surgery for lymphoma in the right trigone, meningioma in the left trigone, and focal enhancing nodule in the right paratrigonal area, respectively. In case of lymphoma, preoperative examination showed a left homonymous hemianopsia : one week later after surgery, a visual field examination was performed and revealed improvement of the visual field defect. In case of the meningioma, the preoperative examination showed no visual field defect : one month later, the visual field had no defect. In case of the enhancing nodule, preoperative visual field testing revealed a partial left homonymous hemianopsia. Visual examination within one month after surgery showed no visual field defect. All three patients treated with the modified trans-MTG approach showed no visual deterioration after surgery. CONCLUSION: The modified trans-MTG approach provides a safe and useful technique for trigonal tumors without postoperative visual field deterioration and affords adequate exposure of the trigonal tumor with a short trajectory. PMID- 22323946 TI - How do you use bispectral index effectively for preventing re-awareness during general anesthesia? PMID- 22323947 TI - Institutional review board (IRB) and ethical issues in clinical research. AB - Clinical research has expanded tremendously in the past few decades and consequently there has been growing interest in the ethical guidelines that are being followed for the protection of human subjects. This review summarizes historical scandals and social responses chronologically from World War II to the Death of Ellen Roche (2001) to emphasize the lessons we must learn from history. International ethical guidelines for studies with human subjects are also briefly described in order to understand the circumstances of clinical research. The tasks and responsibilities of the institutions and investigators in human subject research to preserve the safety and welfare of research subjects are summarized. Next, several debated ethical issues and insights are arranged as controversial topics. This brief review and summary seeks to highlight important arguments and make suggestions to institutional review boards (IRBs) to contribute to the future evolution of ethics in clinical research as we advance forward. PMID- 22323948 TI - Bispectral index and their relation with consciousness of the patients who receive desflurane or sevoflurane anesthesia during wake-up test for spinal surgery for correction. AB - BACKGROUND: Wake-up tests may be necessary during surgery for kypho-scoliosis to ensure that spinal function remains intact. It is difficult to predict the time when patients can respond to a verbal command. We evaluated the effectiveness of the bispectral index (BIS) and its relation to patients' levels of consciousness in wake-up tests during desflurane and sevoflurane anesthesia. METHODS: Eighteen patients each were enrolled in the desflurane and sevoflurane groups for spinal correction surgery. We measured BIS values, blood pressure, heart rate, and consciousness state and time, at the points when patients responded during the wake-up test. RESULTS: The BIS values when patients made fists upon a verbal command (T3) were 86.7 +/- 7.5 for desflurane and 90.3 +/- 5.4 for sevoflurane. Patients in the desflurane group had significantly shorter wake up delays than those in the sevoflurane group (6.9 +/- 1.8 min vs. 11.8 +/- 3.6 min). However, there was no difference between the groups in the time between the response to a verbal command and the time when a patient moved their toes in response to verbal commands. No recall of the wake-up tests occurred in either group. CONCLUSIONS: The values obtained using the BIS index could to some extent predict the time of a patient's and would be informative during desflurane and sevoflurane anesthesia. Moreover, desflurane permitted faster responses to verbal commands than sevoflurane, and allowed the wake-up test to be performed sooner. PMID- 22323949 TI - Effect of flumazenil on recovery from anesthesia and the bispectral index after sevoflurane/fentanyl general anesthesia in unpremedicated patients. AB - BACKGROUND: Benzodiazepines have a hypnotic/sedative effect through the inhibitory action of gamma-aminobutyric acid type A receptor. Flumazenil antagonizes these effects via competitive inhibition, so it has been used to reverse the effect of benzodiazepines. Recently, flumazenil has been reported to expedite recovery from propofol/remifentanil and sevoflurane/remifentanil anesthesia without benzodiazepines. Endogenous benzodiazepine ligands (endozepines) were isolated in several tissues of individuals who had not received benzodiazepines. METHODS: Forty-five healthy unpremedicated patients were randomly allocated to either flumazenil or a control groups. Each patient received either a single dose of 0.3 mg of flumazenil (n = 24) or placebo (n = 21). After drug administration, various recovery parameters and bispectral index (BIS) values in the flumazenil and control groups were compared. RESULTS: Mean time to spontaneous respiration, eye opening on verbal command, hand squeezing on verbal command, extubation and time to date of birth recollection were significantly shorter in the flumazenil group than in the control group (P = 0.004, 0.007, 0.005, 0.042, and 0.016, respectively). The BIS value was significantly higher in flumazenil group than in the control group beginning 6 min after flumazenil administration. CONCLUSIONS: Administration of a single dose of 0.3 mg of flumazenil to healthy, unpremedicated patients at the end of sevoflurane/fentanyl anesthesia without benzodiazepines resulted in earlier emergence from anesthesia and an increase in the BIS value. This may indicate that flumazenil could have an antagonistic effect on sevoflurane or an analeptic effect through endozepine-dependent mechanisms. PMID- 22323950 TI - Clinical comparisons of 0.5% and 0.375% levobupivacaine for ultrasound-guided axillary brachial plexus block with nerve stimulation. AB - BACKGROUND: In an axillary brachial plexus block (ABPB), where relatively large doses of local anesthetics are administered, levobupivacaine is preferred due to a greater margin of safety. However, the efficacy of levobupivacaine in ABPB has not been studied much. We performed a prospective, double-blinded study to compare the clinical effect of 0.375% levobupivacaine with 0.5% levobupivacaine for ultrasound (US)-guided ABPB with nerve stimulation. METHODS: FORTY PATIENTS UNDERGOING ELECTIVE UPPER LIMB SURGERY WERE RANDOMIZED INTO TWO GROUPS: Group I (0.375% levobupivacaine) and Group II (0.5% levobupivacaine). All four main terminal nerves of the brachial plexus were blocked separately with 7 ml of levobupivacaine using US guidance with nerve stimulation according to study group. A blinded observer recorded the onset time for sensory and motor block, elapsed time to be ready for surgery, recovery time for sensory and motor block, quality of anesthesia, patient satisfaction and complications. RESULTS: There were no significant differences in the time to find nerve locations, time to perform block and number of skin punctures between groups. Insufficient block was reported in one patient of Group I, but no failed block was reported in either group. There were no differences in the onset time for sensory and motor block, elapsed time to be ready for surgery, patient satisfaction and complications. CONCLUSIONS: 0.375% levobupivacaine produced adequate anesthesia for ABPB using US guidance with nerve stimulation, without any clinically significant differences compared to 0.5% levobupivacaine. PMID- 22323951 TI - Effects of interscalene brachial plexus block to intra-operative hemodynamics and postoperative pain for arthroscopic shoulder surgery. AB - BACKGROUND: Although arthroscopic shoulder surgery is less invasive and painful than open shoulder surgery, it can often cause intra-operative hemodynamic instability and severe post-operative pain. This study was conducted to investigate the efficacy of the interscalene brachial plexus block (IBPB) on intra-operative hemodynamic changes and post-operative pain during arthroscopic shoulder surgery. METHODS: After institutional review board approval, 50 consecutive patients that had undergone arthroscopic shoulder surgery under general anesthesia were randomly assigned to one of two groups to evaluate intra operative hemodynamic changes and post-operative pain control. Group 1 patients received an IBPB with 10 ml of normal saline guided by a nerve stimulator before induction, and Group 2 patients received 10 ml of 0.5% ropivacaine hydrochloride with the same technique. The heart rate and systolic and diastolic blood pressures were recorded before the incision and 1, 3, 5, 10, and 20 minutes after the incision. Pre-operative and post-operative pain was evaluated with a visual analog scale 1, 3, 6, 12, and 24 hours after surgery. The patients were given tramadol as a rescue medication option. The total volume of tramadol that was injected was also evaluated over the same intervals. RESULTS: Group 2 showed significantly lower systolic and diastolic blood pressures and heart rates intra operatively compared to Group 1 (P < 0.05). The visual analog scale pain scores, except at 24 hours after surgery, were significantly lower in Group 2 (P < 0.05). The total tramadol consumption significantly reduced in Group 2 (P < 0.05). CONCLUSIONS: IBPB effectively controlled the hemodynamic changes that occurred during arthroscopic shoulder surgery as well as post-operative pain. PMID- 22323952 TI - Comparison of hemodynamic changes between phenylephrine and combined phenylephrine and glycopyrrolate groups after spinal anesthesia for cesarean delivery. AB - BACKGROUND: Hypotension remains a common clinical problem of spinal anesthesia for cesarean delivery and phenylephrine is used as a vasopressor to address this. However, phenylephrine reduces maternal cardiac output (CO) due to reflex bradycardia. Glycopyrrolate is safe for the fetus, and increases heart rate (HR). Using a noninvasive measure of CO, we compared maternal hemodynamic changes between the phenylephrine only group (group P) and the phenylephrine plus glycopyrrolate group (group PG). METHODS: In this randomized study, 60 women scheduled for elective cesarean delivery were allocated to group P (n = 30) or group PG (n = 30). In both groups, phenylephrine was infused at 50 ug/min. This infusions stopped if systolic blood pressure (SBP) was higher than the baseline value, and phenylephrine 100 ug was injected if SBP was lower than 80% of the baseline value from spinal anesthesia to delivery. In group PG, glycopyrrolate 0.2 mg was injected intravenously after spinal anesthesia. Hemodynamic parameters, such as SBP, heart rate (HR), stroke volume index (SVI), cardiac index (CI) were measured before and until 15 min after spinal anesthesia. RESULTS: There were no significant differences in SBP and SVI compared to the baseline value in each group and between the two groups. HR and CI reduced significantly from 8 min to 15 min in group P compared to the baseline value as well as group PG for each time-point. However, HR and CI were maintained in group PG. CONCLUSIONS: The use of glycopyrrolate added to phenylephrine infusion to prevent hypotension by spinal anesthesia for cesarean delivery was effective in maintaining HR and CI. PMID- 22323953 TI - A questionnaire study investigating the prevalence of chronic postoperative pain. AB - BACKGROUND: Chronic postoperative pain (CPOP) is defined as pain of at least 2 months duration after a surgical procedure. Until recently, it has been a neglected topic, because it can occur after a wide spectrum of operations; however, little is known regarding its underlying mechanism, prevalence, risk factors, and treatments. We investigated characteristics of CPOP after various operations via a questionnaire. METHODS: Patients were contacted at > 2 months after surgery, irrespective of sex, type of operation or anesthesia method, and a follow-up pain questionnaire was administered by phone. RESULTS: One hundred forty-five of 400 patients (36.3%) described CPOP. The prevalence of CPOP was significantly lower in laparoscopic surgery (29/159, 18.2%) than open surgery (116/241, 48.1%). The prevalence of CPOP was higher with the use of PCA (patient controlled analgesia), (45.3%) than without PCA (24.6%). There were no significant differences regarding sex, anesthetic method, or duration of operation. CONCLUSIONS: Our results indicate that the prevalence of CPOP may be related to use of an endoscope and PCA. However, it is difficult to completely explain the correlation, because this is a complex area of research. More research is needed to improve the quality of pain relief. PMID- 22323954 TI - Effect of continuous psoas compartment block and intravenous patient controlled analgesia on postoperative pain control after total knee arthroplasty. AB - BACKGROUND: Total knee arthroplasty (TKA) generates severe postoperative pain in 60% of patients and moderate pain in 30% of patients. Because inadequate postoperative pain control can hinder early physiotherapy and rehabilitation, it is the most influential factor dictating a good outcome. The purpose of this study was to evaluate the effectiveness of continuous psoas compartment block (PCB) in comparison to intravenous patient-controlled analgesia (IVPCA) in TKA patients. METHODS: 40 TKA patients were randomly divided into 2 groups. Group IVPCA (n = 20) received intravenous patient controlled analgesia (IVPCA) for 48 hours. Group PCB (n = 20) received continuous PCB for 48 hours at the fourth intertransverse process of the lumbar using the C-arm. Pain scores, side effects, satisfaction, the length of hospital stay, rescue antiemetics, and analgesics were recorded. RESULTS: Pain scores (VNRS 0-100) were higher in Group IVPCA than in Group PCB. Nausea and sedation occurred more frequently in Group IVPCA than in Group PCB. There were no differences between the groups in the length of the hospital stay, satisfaction scores, and the use of rescue antiemetics and analgesics. CONCLUSIONS: Continuous PCB seemed to be an appropriate and reliable technique for TKA patients, because it provided better analgesia and fewer side effects such as nausea and sedation when compared to IVPCA. PMID- 22323955 TI - Effect of warmed ropivacaine solution on onset and duration of axillary block. AB - BACKGROUND: Bicarbonate, as an adjunct increasing the non-ionized form of local anesthetics, can reduce latency and prolong duration of regional nerve block. Warming of local anesthetics decreases pKa and also increases the non-ionized form of local anesthetics. We warmed ropivacaine to body temperature (37C) and evaluated the sensory block onset time, motor block onset time and analgesic duration of axillary block. METHODS: Patients were consecutively allocated to two groups of 22 patients each. Ropivacaine 150 mg (30 ml) at 20C (room temperature) and 150 mg (30 ml) at 37C (body temperature) was injected in group 1 and group 2, respectively. Sensory block and motor block was assessed every 5 minutes, for 30 minutes after injection. The duration of analgesia was recorded after operation. RESULTS: In group 2, the onset times of both sensory and motor block of the radial, ulnar, median and musculocutaneous nerves were significantly reduced, compared to group 1. Also, the number of blocked nerves was increased in group 2, within 30 minutes after injection. Analgesia lasted for 2 hours longer in group 2, compared to group 1, but the difference was not statistically significant (P > 0.05). CONCLUSIONS: Warming of ropivacaine to 37C can reduce the onset time of both sensory and motor block, during axillary block. PMID- 22323956 TI - Evaluation of the neurological safety of epidurally-administered pregabalin in rats. AB - BACKGROUND: The primary site of action of pregabalin, i.e. the alpha-2-delta subunit of the voltage-dependent calcium channel, is located at the dorsal root ganglion and dorsal horn of the spinal cord. Therefore, the epidural administration of pregabalin could have advantages over oral administration. However, the possibility of its neurotoxicity should be excluded before any attempt at epidural administration. We evaluated the neuronal safety of epidurally-administered pregabalin by observing the sensory/motor changes and examining the histopathology of spinal cord in rats. METHODS: Sixty rats of 180 230 g were divided into three groups; 3 mg of pregabalin dissolved in 0.3 ml saline (group P, n = 20), 0.3 ml 40% alcohol (group A, n = 20), or 0.3 ml normal saline (group N, n = 20) was administered epidurally to the rats in each group. Pinch-toe test, motor function evaluation, and histopathologic examination of vacuolation, chromatolysis, meningeal inflammation, and neuritis were performed at the 1st, 3rd, 7th, and 21st day after each epidural administration. RESULTS: All rats enrolled in group P, like those in group N, showed neither sensory/motor dysfunction nor any histopathological abnormality over the 3-week observation period. In contrast, in group A, 80% of the rats showed abnormal response to the pinch-toe test and all rats showed decreased motor function during the entire evaluation period. In addition, all histopathologic findings of neurotoxicity were observed exclusively in group A. CONCLUSIONS: The epidurally administered pregabalin (about 15 mg/kg) did not cause any neurotoxic evidence, in terms of both sensory/motor function evaluation and histopathological examination in rats. PMID- 22323957 TI - Gender differences in paclitaxel-induced neuropathic pain behavior and analgesic response in rats. AB - BACKGROUND: Females show greater sensitivity than males to several modalities of experimental pain. However, the gender differences in paclitaxel-induced neuropathic pain have not been studied. The current study examined the gender differences in neuropathic pain behavior and the effect of analgesics in a paclitaxel-induced neuropathic pain model in rats. METHODS: Neuropathic pain was induced by intraperitoneal injection of paclitaxel (2 mg/kg) on 4 alternate days in Sprague-Dawley rats of both genders. Mechanical allodynia was measured using a von Frey filament. The gender differences in analgesic responses were determined after administration of morphine (2 or 5 mg/kg), ketamine (2 or 5 mg/kg), or combined morphine (2 mg/kg) and ketamine (2 mg/kg). RESULTS: Paclitaxel induced mechanical allodynia, which began to manifest on day 4, peaked within 10 days, and plateaued for at least 2 months after the first paclitaxel injection. No gender difference in the manifestation of mechanical allodynia was observed. A 2 mg/kg dose of ketamine increased the mechanical threshold only in males. The 5 mg/kg dose of ketamine significantly increased the mechanical threshold in both genders. Morphine (2 and 5 mg/kg) dose-dependently increased the mechanical thresholds in both genders. The 2 mg/kg dose of ketamine enhanced the antinociceptive effect of 2 mg/kg morphine only in females. CONCLUSIONS: No gender difference in paclitaxel-induced neuropathic pain or analgesic response to ketamine or morphine was observed in Sprague-Dawley rats. Low dose ketamine enhanced the analgesic effect of morphine on paclitaxel-induced mechanical allodynia but only in female rats. PMID- 22323958 TI - "Possible TRALI" developed during bilateral total knee arthroplasty replacement A case report-. AB - Transfusion-related acute lung injury (TRALI) is one of the leading causes of transfusion-related morbidity and mortality. However, it is frequently not diagnosed and under-reported, which could result in inappropriate treatment. Diagnostic definition for TRALI consists of hypoxia and bilateral pulmonary edema occurring during or within 6 hours of a transfusion in the absence of cardiac failure or intravascular volume overload. Here, we report a fatal case, which resulted from under-recognition and misdiagnosis of TRALI occurring during transfusion with packed red blood cells during a bilateral total knee replacement. PMID- 22323959 TI - Stress-induced cardiomyopathy after negative pressure pulmonary edema during emergence from anesthesia -A case report-. AB - Stress-induced cardiomyopathy (SICM) presenting as an acute myocardial dysfunction is characterized by transient left ventricular wall motion abnormality, which has been known to be associated with excessive catecholamine production caused due to various types of stress. Sympathetic hyperactivity is common during the perioperative period, and reports of SICM occurring during this period have actually increased. We present a case of SICM following negative pressure pulmonary edema due to upper airway obstruction during emergence from anesthesia. Excessive catecholamine release in response to respiratory difficulty could have been the underlying inciting factor. PMID- 22323960 TI - A case report of anesthesia management in the liver transplantation recipient with porphyria -A case report-. AB - Porphyrias are a group of diseases characterized by an enzyme deficiency in the heme biosynthesis pathway, resulting in accumulation of precursor molecules in the tissue. Some porphyric patients develop progressive liver disease that requires liver transplantation. This case report describes special anesthetic challenges, including careful selection of drugs and the use of special filters that can exclude harmful wavelengths of ultraviolet, in a patient with porphyria who underwent living donor liver transplantation. Understanding the patient's status and disease process, and avoiding triggering factors of porphyria attacks, are important for successful liver transplantation anesthesia in patients with porphyria. PMID- 22323961 TI - Cardiac arrest from intravenous indigo carmine during laparoscopic surgery -A case report-. AB - Indigo carmine (sodium indigotindisulfonate) is a safe, biologically inactive blue dye routinely administered intravascularly during urologic and gynecologic procedures to localize the ureteral orifices and to identify severed ureters and fistulous communications. We report a case of hypotension, cardiac arrest, and cerebral ischemia after the administration of indigo carmine in a patient under total laparoscopic hysterectomy. PMID- 22323962 TI - Severe hypotension following urethral catheterization during general anesthesia in a patient with bladder cancer -A case report-. AB - The process of micturition is related to activation of the cardiovascular autonomic nervous system. Hypotension with bradycardia often occurs during or immediately after micturition. We experienced a case of sudden severe hypotension and bradycardia following urethral catheterization in a patient who underwent an urethral dilatation and transurethral resection of bladder tumor while under general anesthesia. The patient was treated with inotropics and intravenous fluids, and he recovered without any complications. The characteristics of this case are similar to the physiologic changes that occur in micturition syncope. Therefore, it is presumed that the autonomic reflex that was triggered by the urethral catheterization caused the hypotension and bradycardia. PMID- 22323963 TI - High dose ropivacaine-induced toxicity after infraclavicular block. PMID- 22323964 TI - Changes in the bispectral index and cerebral oxygen saturation during neuroendovascular intervention under general anesthesia. PMID- 22323965 TI - Tongue laceration during electroconvulsive therapy. PMID- 22323966 TI - Disorders of sex development. AB - The birth of a new baby is one of the most dramatic events in a family, and the first question is usually "is it a boy or a girl?" The newborn infant with ambiguous external genitalia often comes as a surprise for the doctors as well as the parents and is sometimes described as an endocrine emergency situation presenting a problem of sex assignment. The nomenclature such as 'intersex', 'hermaphrodite', and 'pseudohermaphrodite' is out of date as well as confusing, and many urologists are concerned that these confusing terms could be perceived to be pejorative by some affected families. In response to concerns regarding outdated and controversial terms, the Chicago Consensus held in 2005 recommended new terminology based on the umbrella term disorders of sex differentiation (DSDs). The term DSD has a comprehensive definition including any problem noted at birth in which the genitalia are atypical in relation to the chromosomes or gonads. The karyotype is used as a prefix defining the classification of DSD. DSDs are rare and complex. The optimal management of patients with DSD must be individualized and multidisciplinary, considering all aspects, including psychological care and full disclosure of alternatives relating to surgery type and timing. Although further studies are necessary to confirm guidelines and recommendations fitting for the individual patients with DSD, this article is an attempt to provide a balanced perspective for new taxonomy, clinical evaluation, and medical, surgical, and psychological management of DSD. PMID- 22323967 TI - Usefulness of preoperative serum testosterone as a predictor of extraprostatic extension and biochemical recurrence. AB - PURPOSE: A great variety of studies on preoperative serum testosterone as a predictor of progression of prostate cancer have been reported recently. The purpose of this study was to investigate the relationship of preoperative serum testosterone levels in patients who underwent radical prostatectomy with prognostic factors. MATERIALS AND METHODS: Clinical data were collected from 60 patients who underwent radical prostatectomy. The 60 cases were divided into 2 groups according to their preoperative serum testosterone levels: group 1 (n=21), <3 ng/ml; group 2 (n=39), >=3 ng/ml. The groups were compared according to prog ression factors. Multivariate logistic regression analysis was performed to determine the correlation between biochemical recurrence and each variable. RESULTS: The incidence of extraprostatic invasions was significantly higher in group 1 with 13 cases in group 1 (61.9%) and 11 cases in group 2 (28.2%) (p=0.011). The incidence of biochemical recurrence was also significantly higher in group 1 with 5 cases in group 1 (23.8%) and 2 cases in group 2 (5.1%) (p=0.032). A low serum testosterone level (<=3 ng/ml) was associated with an increased risk of biochemical recurrence (odds ratio [OR], 13.64; 95% confidence interval [CI], 1.66 to 2.43; p=0.015) and an increased risk of extraprostatic invasions (OR, 4.96; 95% CI, 1.41 to 17.38; p=0.012). CONCLUSIONS: The incidence rates of extraprostatic invasions and biochemical recurrence were significantly higher in the group with preoperative average serum testosterone of less than 3 ng/ml. Therefore, these results suggest that preoperative average serum testosterone will be useful in predicting postoperative prostate cancer progression. PMID- 22323968 TI - Pattern of lymph node metastasis correlates with tumor location in bladder cancer. AB - PURPOSE: Resection of a large number of lymph nodes (LNs) increases survival in patients with LN-positive disease; however, morbidity also increases. Here, we investigated the correlation between tumor location and LN metastasis in bladder cancer. MATERIALS AND METHODS: Thirty-six patients with pathological N1 or higher bladder cancer, who underwent radical cystectomy with extended lymphadenectomy, were reviewed retrospectively. The tumor location was classified as right, left, front, posterior, or whole bladder. The LN metastasis pattern was classified as right, left, or bilateral. The correlation between tumor location and LN metastasis was determined by chi-square test. Survival rates were compared by Kaplan-Meier analysis. RESULTS: The numbers of patients with a tumor on the right (group 1), left (group 2), posterior (group 3), or whole (group 4) bladder were 16 (44.4%), 16 (44.4%), 2 (5.6%), and 2 (5.6%), respectively. In group 1, 14 patients (87.5%) had right-sided ipsilateral LNs, and 2 patients (12.5%) had left sided contralateral LNs. In group 2, 4 patients (25%) had right-sided contralateral LNs, and 12 patients (75%) had left-sided ipsilateral LNs. In group 3, both patients (100%) had right-sided posterior LNs. In group 4, both patients (100%) had positive LNs on both sides. Tumor location and LN metastasis were significantly correlated (p<0.05). Moreover, the survival rate was significantly higher in patients with no LN metastasis than in patients with ipsilateral or contralateral LN-positive bladder cancer. CONCLUSIONS: The location of the bladder tumor and direction of metastatic spread were significantly correlated. Mandatory bilateral lymphadenectomy during radical cystectomy should be questioned. PMID- 22323969 TI - Predicting factors for death from other causes in patients with localized renal cell carcinoma. AB - PURPOSE: To identify the predictors of death from other causes in patients with localized renal cell carcinoma (RCC). MATERIALS AND METHODS: We identified 1,101 patients with pathologically confirmed T1 or T2 RCC with a follow-up duration of over 6 months. Survival according to the cause of death was evaluated by using the Kaplan-Meier analysis with log-rank test. Prognostic factors for death from other causes were assessed by multivariate analysis using the Cox proportional hazard regression model. Once the prognostic factors were identified, a risk group variable was created by counting the number of unfavorable features present for each patient. RESULTS: The median follow-up was 62 months, and RCC-related death occurred in 50 patients (4.5%), whereas death from other causes occurred in 47 (4.3%). Patients who died from other causes had a higher American Society of Anesthesiologist (ASA) score (26.1% vs. 10.2%; p=0.044), older age (63.4 years vs. 55.0 years; p<0.001), smaller mass size (5.1 cm vs. 7.9 cm; p<0.001), and lower nuclear grade (p=0.003). In the multivariate Cox regression analysis, older age, higher ASA score, and lower body mass index were independent factors predicting death from other causes in patients with localized RCC. On the basis of the number of risk factors for death from other causes, the 5-year other-cause specific survival was 98.3% (0 risk factors), 84.7% (1 risk factor), and 67.6% (2 or 3 risk factors), respectively (p<0.001). CONCLUSIONS: Older age, higher ASA score, and lower body mass index were independent predictors of death from other causes in patients with localized RCC. PMID- 22323970 TI - Impact of changing trends in medical therapy on surgery for benign prostatic hyperplasia over two decades. AB - PURPOSE: Following the introduction of medical therapy for benign prostatic hyperplasia (BPH), we determined the effect of the change in trends in medical therapy on the indication and outcome of surgical intervention for BPH. MATERIALS AND METHODS: We compared the basic characteristics of, weight of resected tissue of, transfusions in, and postoperative complications of patients who underwent surgery between 1985 and 1989 (before the advent of medical therapy for BPH), between 1995 and 1999 (when medical therapy was developed and became widely used as alternative treatment), and between 2005 and 2009 (when medical therapy superseded surgical intervention to become first-line treatment and when combination therapy became widely adopted). RESULTS: At our institution, the mean age and BMI of patients increased over the past two decades (p<0.001). Hypertension, operation history, and other comorbidities also increased significantly (p<0.001, p=0.005, and p<0.001, respectively). The indications for surgery in 1985 to 1989, 1995 to 1999, and 2005 to 2009 were as follows: acute urinary retention in 34.7%, 20.2%, and 15.1% of patients and symptomatic deterioration in 61.1%, 72.3%, and 73.0% of patients, respectively. Prostate volume and the weight of resected tissue increased from 34.4+/-14.5 ml to 61.3+/ 32.4 ml and from 7.2+/-6.4 g to 10.8+/-7.6 g, respectively, over two decades. Patients who underwent surgery in 2005 to 2009 had their catheters removed earlier (p<0.001). Secondary hemorrhage within four postoperative weeks and repeat transurethral resection of the prostate within 1 year decreased significantly (p=0.03 and p=0.003, respectively). No statistically significant change in impaired detrusor contractility was found (p=0.523). CONCLUSIONS: Although patients who underwent surgery were older after widespread use of medical therapy for BPH, advancements in surgical techniques have benefitted these patients. PMID- 22323971 TI - Effect of Bladder Neck Preservation and Posterior Urethral Reconstruction during Robot-Assisted Laparoscopic Radical Prostatectomy for Urinary Continence. AB - PURPOSE: To report our results on urinary continence after bladder neck preservation (BNP) and posterior urethral reconstruction (PUR) during robot assisted laparoscopic radical prostatectomy (RALP). MATERIALS AND METHODS: Data from 107 patients who underwent RALP were compared on the basis of whether the patients underwent BNP and PUR, BNP only, or the standard technique (ST). In group A (n=31 patients), ST was performed by using Ven velthoven continuous suturing for urethrovesical anastomosis. In group B (n=28 patients), ST with only PUR was performed. In group C (n=48 patients), both the BNP and PUR techniques were used. "Recovery of continence" was defined as the use of 1 pad (50 ml) or less within 24 hours. RESULTS: The three groups were comparable in terms of patient demographics. The mean operative time and the mean blood loss decreased significantly from group A to group C (p=0.021 for mean operative time and p=0.004 for the mean blood loss). Mean catheterization time was 8.9, 7.8, and 7.1 days in each group (p=0.047). Early return of urinary continence at 3 months was observed in group B (89.2%) and group C (90.6%) compared with group A (71%). However, continence at 6 months was comparable in the 3 groups (87.5% in group A, 92.8% in group B, and 92.3% in group C). Rates of positive surgical margins decreased from 30.2% in group A to 20% in group B and 12% in group C. CONCLUSIONS: BNP and PUR during RALP showed a favorable impact on the early postoperative recovery of continence while not affecting positive surgical margins. PMID- 22323972 TI - Acute postoperative pain after ureteroscopic removal of stone: incidence and risk factors. AB - PURPOSE: Ureteroscopic removal of stones (URS) has been widely used to treat ureteral stones because it is comparatively safe, has a high success rate, and enables patients to rapidly return to their daily routines. However, some patients experience pain after URS, but the incidence of acute post-URS pain remains largely unknown. This study aimed to investigate the incidence of acute postoperative pain after URS and the associated risk factors. MATERIALS AND METHODS: Data for 143 consecutive patients who underwent URS from June 2008 to December 2010 were collected. After excluding 8 patients who developed intraoperative complications, the patients were divided into two groups according to postoperative pain on the first postoperative day. Acute postoperative pain was defined as a pain score greater than 4 on a visual analogue pain scale (normal range, 0 to 10). Various factors were analyzed to identify the risk factors that could predict acute postoperative pain after URS. RESULTS: The stone free rate without URS intraoperative complications was 95.5%. A total of 21 (14.6%) patients experienced postoperative pain on the first postoperative day. Young age, psychiatric illness, history of urinary tract infection, use of a stone basket, large stone size, and prolonged operation time were identified as risk factors for acute postoperative pain. CONCLUSIONS: The incidence of acute postoperative pain is not that low and should not be overlooked, because it is associated with postoperative complications that could result in an unscheduled hospital admission or visit. Active pain control should be contemplated after URS in young patients and in those with a history of urinary tract infection, psychiatric illness, large stone size, and prolonged operation time. PMID- 22323973 TI - Analyzing the effect of distance from skin to stone by computed tomography scan on the extracorporeal shock wave lithotripsy stone-free rate of renal stones. AB - PURPOSE: To determine whether the distance from skin to stone, as measured by computed tomography (CT) scans, could affect the stone-free rate achieved via extracorporeal shock wave lithotripsy (ESWL) in renal stone patients. MATERIALS AND METHODS: We retrospectively reviewed the records 573 patients who had undergone ESWL at our institution between January 2006 and January 2010 for urinary stones sized from about 5 mm to 20 mm and who had no evidence of stone movement. We excluded patients with ureteral catheters and percutaneous nephrostomy patients; ultimately, only 43 patients fulfilled our inclusion criteria. We classified the success group as those patients whose stones had disappeared on a CT scan or simple X-ray within 6 weeks after ESWL and the failure group as those patients in whom residual stone fragments remained on a CT scan or simple X-ray after 6 weeks. We analyzed the differences between the two groups in age, sex, size of stone, skin-to-stone distance (SSD), stone location, density (Hounsfield unit: HU), voltage (kV), and the number of shocks delivered. RESULTS: The success group included 33 patients and the failure group included 10. In the univariate and multivariate analysis, age, sex, size of stone, stone location, HU, kV and the number of shocks delivered did not differ significantly between the two groups. Only SSD was a factor influencing success: the success group clearly had a shorter SSD (78.25+/-12.15 mm) than did the failure group (92.03+/-14.51 mm). The results of the multivariate logistic regression analysis showed SSD to be the only significant independent predictor of the ESWL stone free rate. CONCLUSIONS: SSD can be readily measured by CT scan; the ESWL stone free rate was inversely proportional to SSD in renal stone patients. SSD may therefore be a useful clinical predictive factor of the success of ESWL on renal stones. PMID- 22323974 TI - Activin Receptor-Like Kinase 5 Inhibitor Attenuates Fibrosis in Fibroblasts Derived from Peyronie's Plaque. AB - PURPOSE: Transforming growth factor-beta1 (TGF-beta1) is the key fibrogenic cytokine associated with Peyronie's disease (PD). The aim of this study was to determine the antifibrotic effect of 3-((5-(6-Methylpyridin-2-yl)-4-(quinoxalin-6 yl)-1H-imidazol-2-yl) methyl)benzamide (IN-1130), a small-molecule inhibitor of the TGF-beta type I receptor activin receptor-like kinase 5 (ALK5), in fibroblasts isolated from human PD plaque. MATERIALS AND METHODS: Plaque tissue from a patient with PD was used for primary fibroblast culture, and we then characterized primary cultured cells. Fibroblasts were pretreated with IN-1130 (10 uM) and then stimulated with TGF-beta1 protein (10 ng/ml). We determined the inhibitory effect of IN-1130 on TGF-beta1-induced phosphorylation of Smad2 and Smad3 or the nuclear translocation of Smad proteins in fibroblasts. Western blot analyses for plasminogen activator inhibitor-1, fibronectin, collagen I, and collagen IV were performed to evaluate effect of IN-1130 on the production of extracellular matrix proteins. RESULTS: The treatment of fibroblasts with TGF beta1 significantly increased phosphorylation of Smad2 and Smad3 and induced translocation of Smad proteins from the cytoplasm to the nucleus. Pretreatment with IN-1130 substantially inhibited TGF-beta1-induced phosphorylation of Smad2 and Smad3 and nuclear accumulation of Smad proteins. The TGF-beta1-induced production of extracellular matrix proteins was also significantly inhibited by treatment with IN-1130 and returned to basal levels. CONCLUSIONS: Overexpression of TGF-beta and activation of Smad transcriptional factors are known to play a crucial role in the pathogenesis of PD. Thus, inhibition of the TGF-beta signaling pathway by ALK5 inhibitor may represent a promising therapeutic strategy for treating PD. PMID- 22323975 TI - A prospective study of reducing unnecessary prostate biopsy in patients with high serum prostate-specific antigen with consideration of prostatic inflammation. AB - PURPOSE: We aimed to reduce unnecessary prostatic biopsy in patients with high prostate-specific antigen (PSA) by consideration of prostatic inflammation. MATERIALS AND METHODS: The investigation was conducted prospectively in 413 patients with a PSA level of 4 to 10 ng/ml from January 2004 to December 2009. All patients underwent the expressed prostatic secretion (EPS) or voided bladder urine 3 (VB3) test to be classified into two groups: positive group and negative group. Patients with a positive result on the EPS or VB3 test were treated with antibiotics for 2 months, and in cases in which the PSA level remained high, we performed prostate biopsy. In patients with a negative result on the VB3 test, we performed prostate biopsy directly. RESULTS: Of the 413 study patients, 215 (52%) patients had positive findings on the EPS or VB3 test. After 8 weeks of antibiotics therapy, 53 of the 215 men avoided prostate biopsy because their PSA level was normalized. The other patients (162 of 215) still had elevated PSA levels of more than 4 ng/ml, including 7 patients in whom the biopsy revealed cancer. Patients with negative findings (198 of 413) underwent prostate biopsy. Of the 198 patients, 41 were diagnosed with prostate cancer. The total prostate cancer detection rate was 11.6% in our subjects, where as it was 20.7% in the patients with negative findings on the EPS or VB3 and 3.3% in the patients with positive findings, respectively. CONCLUSIONS: In cases in which the PSA level is increasing, if we first exclude prostatitis and carry out a serial diagnostic procedure, it may help to reduce unnecessary prostatic biopsy. PMID- 22323976 TI - Complication rates of the 720 video-assisted minilaparotomy living donor nephrectomies: supplementing clavien classification. AB - PURPOSE: Laparoscopic living donor nephrectomy (LLDN) has been reported to be as safe and effective as open surgery. We systematically evaluated the safety of video-assisted minilaparotomy surgery-living donor nephrectomy (VAMS-LDN) with use of the modified Clavien classification. MATERIALS AND METHODS: We retrospectively analyzed complications in 720 cases of VAMS-LDN conducted in our institute from 2003 to 2010 by use of the modified Clavien classification of surgical complications. RESULTS: The mean age of the donors was 39.3 years (range, 16 to 66 years) and their mean body mass index was 23.3 kg/m(2) (range, 15.8 to 36.4 kg/m(2)). A total of 67 complications occurred (9.3%). Based on the modified Clavien classification, grade 1, 2a, and 2b complications occurred in 49 (6.8%), 16 (2.2%), and 2 (0.3%) of the donors, respectively. Most grade 1 complications involved mild vascular injuries that were immediately repaired with polypropylene sutures during the surgery. These did not cause any postoperative problems. The other grade 1 complications were wound dehiscence, not requiring secondary closure, and wound site pain in 11 (1.5%) and 5 (0.7%) cases, respectively. Grade 2a complications occurred in 16 (2.2%) cases: 9 (1.3%) involved postoperative transfusions and 1 (0.1%) involved a renal fossa hematoma. One grade 2b complication occurred; it was a lymphocele that resolved with placement of a pigtail catheter. No complications classified as grade 2c or worse occurred. CONCLUSIONS: According to the present analysis of complications, VAMS LDN is a safe procedure with complication rates comparable to those of LLDN as evaluated in previous studies. PMID- 22323977 TI - Floating Hem-o-Lok Clips in the Bladder without Stone Formation after Robot Assisted Laparoscopic Radical Prostatectomy. AB - Hem-o-Lok clips (Weck Surgical Instruments, Teleflex Medical, Durham, NC, USA) are widely used in robot-assisted laparoscopic radical prostatectomy because of their easy application and secure clamping. To date, there have been some reports of intravesical migration of these clips causing urethral erosion, bladder neck contractures, and subsequent calculus formation. We report the first case of bladder migration of Hem-o-Lok clips without stone formation after robot-assisted laparoscopic radical prostatectomy. The Hem-o-Lok clips were found during urethral dilation with a guide wire for bladder neck contracture under cystourethroscopy. The Hem-o-Lok clips were floating in the bladder without stone formation and were removed by a cystoscopic procedure. PMID- 22323978 TI - Skeletal muscle metastases from urothelial cell carcinoma. AB - Hematogenous metastasis to skeletal muscle from urothelial carcinoma is extremely rare and metastatic disease to skeletal muscle tends to be found in people with advanced-stage neoplasm. We report in this paper a case of left sartorius muscle metastasis from urothelial cell carcinoma. A left nephroureterectomy with bladder cuff excision was performed and revealed a high-grade papillary transitional cell carcinoma (TCC) of the pelvis. And 6 month later, recurrent bladder cancer was found regular cystoscopy and then treated with transurethral resection of the bladder. After 6 times resection of bladder, an invasion into the bladder muscle layer was found. We recommended additional radical cystectomy to prevent the disease from advancing. However, the patient refused additional surgery. 6 month later, the patient complained of left thigh pain, so ultrasonography-guided biopsy of the nodular mass lesion in the left sartorius muscle was performed. The pathological analysis of the biopsy specimen revealed poorly differentiated metastatic urothelial carcinoma. PMID- 22323979 TI - Case series of mycobacterium abscessus infections associated with a trigger point injection and epidural block at a rural clinic. AB - OBJECTIVES: The aim of this report is to investigate Mycobacterium abscessus infections at a rural clinic and carry out a surveillance program to determine the extent and source of these infections. METHODS: The authors conducted an active surveillance investigation of 36 patients who had visited the clinic since 1 July 2008. Clinical specimens were collected from the patients and an envirnmental investigation. Pulsed-field gel elctrophoresis (PFGE) was performed for comparing with M. abscessus isolates from the patients. RESULTS: Six specimens were obtained from the 6 patients respectively and 22 environmental samples were obtained. M. abscessus was isolated from the wounds of two patients, and various nosocomial pathogens, but not M. abscessus, were isolated from the surrounding environment. Two strains of M. abscessus from patients were identical as a result of PFGE. CONCLUSION: Infection control education including proper hand hygiene should be emphasized for physicians performing invasive procedures. There also needs to be more attention for invasive procedures management, including trigger point injection and epidural block in rural clinics. PMID- 22323980 TI - Persistent organic pollutants and obesity-related metabolic dysfunction: focusing on type 2 diabetes. AB - Even though obesity is a well-established risk factor of type 2 diabetes, there is emerging evidence that persistent organic pollutants (POPs), a variety of lipophilic chemicals accumulated in adipose tissue, may be critically involved in the pathogenesis of type 2 diabetes. Among various POPs, serum concentrations of organochlorine pesticides and polychlorinated biphenyls (PCBs) were the most strongly and consistently linked to type 2 diabetes in both cross-sectional and prospective studies. In particular, obesity did not seem to be related to type 2 diabetes among persons with very low serum concentrations of POPs, suggesting a more fundamental role of chlorinated POPs in the pathogenesis of type 2 diabetes. These POPs were also associated with obesity, insulin resistance, and adverse lipid profiles like high triglyceride and low high-density lipoprotein (HDL) cholesterol among persons without diabetes, all metabolic dysfunctions commonly observed before developing type 2 diabetes. Recent animal studies supported the findings from epidemiological studies. If all these findings on POPs are true, it suggests that any effort to reduce the external and internal exposure to POPs would be necessary to decrease the social burden of type 2 diabetes. PMID- 22323981 TI - Why do irritable bowel syndrome women often have nausea symptom? PMID- 22323982 TI - The physical activity level in female affects colon transit time. PMID- 22323983 TI - Deglutitive inhibition, latency between swallow and esophageal contractions and primary esophageal motor disorders. AB - Swallowing induces an inhibitory wave that is followed by a contractile wave along the esophageal body. Deglutitive inhibition in the skeletal muscle of the esophagus is controlled in the brain stem whilst in the smooth muscle, an intrinsic peripheral control mechanism is critical. The latency between swallow and contractions is determined by the pattern of activation of the inhibitory and excitatory vagal pathways, the regional gradients of inhibitory and excitatory myenteric nerves, and the intrinsic properties of the smooth muscle. A wave of inhibition precedes a swallow-induced peristaltic contraction in the smooth muscle part of the human oesophagus involving both circular and longitudinal muscles in a peristaltic fashion. Deglutitive inhibition is necessary for drinking liquids which requires multiple rapid swallows (MRS). During MRS the esophageal body remains inhibited until the last of the series of swallows and then a peristaltic contraction wave follows. A normal response to MRS requires indemnity of both inhibitory and excitatory mechanisms and esophageal muscle. MRS has recently been used to assess deglutitive inhibition in patients with esophageal motor disorders. Examples with impairment of deglutitive inhibition are achalasia of the LES and diffuse esophageal spasm. PMID- 22323984 TI - Psychological Co-morbidity in Functional Gastrointestinal Disorders: Epidemiology, Mechanisms and Management. AB - Functional gastrointestinal disorder (FGID) is one of the commonest digestive diseases worldwide and leads to significant morbidity and burden on healthcare resource. The putative bio-psycho-social pathophysiological model for FGID underscores the importance of psychological distress in the pathogenesis of FGID. Concomitant psychological disorders, notably anxiety and depressive disorders, are strongly associated with FGID and these psychological co-morbidities correlate with severity of FGID symptoms. Early life adversity such as sexual and physical abuse is more commonly reported in patients with FGID. There is mounting evidence showing that psychological disorders are commonly associated with abnormal central processing of visceral noxious stimuli. The possible causal link between psychological disorders and FGID involves functional abnormalities in various components of the brain-gut axis, which include hypothalamic-pituitary adrenal system, sympathetic and parasympathetic nervous system, serotonergic and endocannabinoid systems. Moreover, recent studies have also shown that psychological distress may alter the systemic and gut immunity, which is increasingly recognized as a pathophysiologic feature of FGID. Psychotropic agent, in particular antidepressant, and psychological intervention such as cognitive behavioral therapy and meditation have been reported to be effective for alleviation of gastrointestinal symptoms and quality of life in FGID patients. Further studies are needed to evaluate the impact of early detection and management of co-morbid psychological disorders on the long-term clinical outcome and disease course of FGID. PMID- 22323985 TI - Pathophysiologic findings of irritable bowel syndrome in china. AB - The mechanism of irritable bowel syndrome (IBS) is still incompletely understood in the world although large amount of investigations have been carried out on it. There are many studies on the pathophysiology of IBS in China, which has huge amount of population suffering from IBS with special ethnicity and culture, including Mainland China, Hong Kong and Taiwan. We collected the literatures to show the results and discuss whether there were any differences in the pathophysiologic findings between China and other countries, whether there were any differences among different subtypes and how the pathophysiology correlated with the manifestations of patients. Gene polymorphism, disturbances of gastrointestinal motility, visceral hypersensitivity, intestinal infection and inflammation, psychological disturbances, food hypersensitivity and intolerance, and altered gut microflora were reviewed in this paper. Some conflicting outcomes between China and other countries were noted although most of them were similar. PMID- 22323986 TI - Prevalence of hidden gastroparesis in the community: the gastroparesis "iceberg". AB - BACKGROUND/AIMS: The prevalence of diagnosed gastroparesis is 24.2/100,000 inhabitants, but a large group of people with gastroparesis-like symptoms have never had a gastric emptying (GE) test. Some of them may have undiagnosed gastroparesis. Our aim was to estimate the prevalence of hidden gastroparesis in the community. METHODS: The study was conducted in 2 parts: (1) Patients referred for a scintigraphic GE test completed a validated questionnaire (Bowel Disease Questionnaire). Multiple linear regression models to predict 2 hours and 4 hours GE rates were developed. (2) A revised Bowel Disease Questionnaire was mailed to a random sample of 4,194 Olmsted County residents. GE rates were estimated with the models for each subject and delayed GE was considered when they were lower than normal values. Hidden gastroparesis was defined in community subjects with predicted delayed GE that had not been diagnosed with gastroparesis prior to the survey. RESULTS: The regression models for GE rates were constructed using data from 450 patients. In addition to age and gender, the symptoms found significant were nausea/vomiting, early satiety, upper abdominal pain, bloating, loss of appetite and weight loss more than 7 pounds. 2,298 (55%) community subjects returned a questionnaire. Five subjects were excluded due to a prior diagnosis of gastroparesis. When models were applied to the community survey data, 42 (1.8%) subjects were estimated to have delayed GE. CONCLUSIONS: Delayed GE was estimated to occur in 1.8% of community subjects. Since the prevalence of diagnosed gastroparesis is low (0.02%), many subjects with gastroparesis may remain undiagnosed. PMID- 22323987 TI - Economic impact of dyspepsia in rural and urban malaysia: a population-based study. AB - BACKGROUND/AIMS: The economic impact of dyspepsia in regions with a diverse healthcare system remains uncertain. This study aimed to estimate the costs of dyspepsia in a rural and urban population in Malaysia. METHODS: Economic evaluation was performed based on the cost-of-illness method. Resource utilization and quality of life data over a specific time frame, were collected to determine direct, indirect and intangible costs related to dyspepsia. RESULTS: The prevalences of dyspepsia in the rural (n = 2,000) and urban (n = 2,039) populations were 14.6% and 24.3% respectively. Differences in socioeconomic status and healthcare utilisation between both populations were considerable. The cost of dyspepsia per 1,000 population per year was estimated at USD14,816.10 and USD59,282.20 in the rural and urban populations respectively. The cost per quality adjusted life year for dyspepsia in rural and urban adults was USD16.30 and USD69.75, respectively. CONCLUSIONS: The economic impact of dyspepsia is greater in an urban compared to a rural setting. Differences in socioeconomic status and healthcare utilisation between populations are thought to contribute to this difference. PMID- 22323988 TI - The Relationship Between Gastric Myoelectric Activity and SCN5A Mutation Suggesting Sodium Channelopathy in Patients With Brugada Syndrome and Functional Dyspepsia - A Pilot Study. AB - BACKGROUND/AIMS: SCN5A encodes the cardiac-specific Na(V)1.5 sodium channel, and Brugada syndrome is a cardiac conduction disorder associated with sodium channel alpha-subunit (SCN5A) mutation. The SCN5A-encoded Na(V)1.5 channel is also found on gastrointestinal smooth muscle and interstitial cells of Cajal. We investigated the relationship between functional dyspepsia (FD) and SCN5A mutation to evaluate sodium channelopathy in FD. METHODS: Patients with Brugada syndrome or FD were examined using upper endoscopy, electrogastrography (EGG), FD symptom questionnaire based on Rome III criteria and genetic testing for SCN5A mutation. Symptom scores of FD and EGG findings were analyzed according to SCN5A mutation. RESULTS: A total of 17 patients (4 Brugada syndrome and 13 FD) participated in the study. An SCN5A mutation was noted in 75.0% of the patients with Brugada syndrome and in 1 (7.7%) of the patients with FD. Of 4 patients with SCN5A mutation, 2 (50%) had FD. Postprandial tachygastria and bradygastria were noted in 2 (50%) and 1 (25%) of the patients with SCN5A mutation, respectively. The EGG findings were not significantly different between positive and negative mutation in 17 patients. CONCLUSIONS: Although we did not find statistically significant results, we suggest that it is meaningful to attempt to identify differences in symptoms and gastric myoelectric activity according to the presence of an SCN5A mutation by EGG analysis. The relationship between FD and sodium channelopathy should be elucidated in the future by a large-scale study. PMID- 22323989 TI - Colon transit time according to physical activity level in adults. AB - BACKGROUND/AIMS: Physical activity (PA) is associated with a reduced risk of colorectal cancer. Thus, we examined the colon transit time (CTT) according to the physical activity level (PAL) in Korean adults. METHODS: The study subjects were 49 adults: 24 males and 25 females. The subjects used an accelerometer for 7 consecutive days to measure the 1-week PAL. The subjects took a capsule containing 20 radio-opaque markers for 3 days. On the fourth day, a supine abdominal radiography was performed. According to the total activity count of all study subjects, the upper 25%, middle 50% and lower 25% were classified into the high (H), moderate (M) and low (L) physical activity (PA) groups, respectively. RESULTS: The total CTT was significantly longer in the female (25.8 hours) than in the male subjects (7.4 hours) (P = 0.002). In regard to difference on PAL, although there was no significant difference among the male subjects, the right CTT in the female subjects was significantly shorter in H group than in M group (P = 0.048), and the recto-sigmoid CTT was significantly shorter in H group than in L group (P = 0.023). Furthermore, there were significant differences in total CTT between L and M groups (P = 0.022), M and H groups (P = 0.026) and between L and H groups (P = 0.002). CONCLUSIONS: The female, but not male, subjects showed that moderate and high PAL assisted colon transit. PMID- 22323990 TI - Gender Role in Irritable Bowel Syndrome: A Comparison of Irritable Bowel Syndrome Module (ROME III) Between Male and Female Patients. AB - BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a widespread chronic health condition which is significantly more prevalent in women. We conducted a gender difference analysis by comparing findings of men and women to determine whether any significant differences exist or not. METHODS: This single-center study was conducted in Tehran, Iran during 2009-2010. IBS was diagnosed on the basis of Rome III criteria. A simple "10 point" objective questionnaire was used. RESULTS: A total number of 144 IBS patients including 44 (30.6%) males and 100 (69.4%) females with the mean age of 37.50 +/- 11.50 years, were assessed. The only differently observed symptom was nausea which was significantly more prevalent in females (49% vs 18.2%, P < 0.001). The commonest subtype of IBS in male patients was diarrhea predominant IBS (38.6%); while, constipation predominant IBS was the most frequent type among females (38%). Moreover, the frequency of loose, mushy or watery stools within the last 3 months was significantly higher among males (2.11 +/- 1.67 vs 1.37 +/- 1.50, P = 0.009). CONCLUSIONS: We report that gender is important in IBS. Although qualitative comparison of different subtypes of IBS between male and female failed to meet the statistically significant level, the answers to the corresponding questions of ROME III IBS module suggest the higher prevalence of bowel movements and looser stool in males. Moreover, nausea was reported more often by females. PMID- 22323991 TI - Anti-enteric neuronal antibodies and the irritable bowel syndrome. AB - BACKGROUND/AIMS: Functional gastrointestinal disorders are those in which no abnormal metabolic or physical processes, which can account for the symptoms, can be identified. The irritable bowel syndrome (IBS) is a significant functional disorder, which affects 10-20 percent of the population worldwide. Predominant symptoms of IBS are abnormal defecation associated with abdominal pain, both of which may be exacerbated by psychogenic stress. Our study was designed to test a hypothesis that symptoms in a subset of patients with a diagnosis of IBS are associated with an autoimmune degenerative neuropathy in the enteric nervous system. METHODS: Serum was collected from Rome II-IBS patients and controls at the University of North Carolina Functional Gastrointestinal Diseases Center. Assay procedures were immunohistochemical localization of antibody binding to enteric neurons and human protein microarray assay for antigens recognized by antibodies in the sera. RESULTS: Eighty-seven percent of IBS sera and 59% of control sera contained anti-enteric neuronal antibodies. Antibody immunostaining was seen in the nucleus and cytoplasm of neurons in the enteric nervous system. Protein microarray analysis detected antibody reactivity for autoantigens in serum with anti-enteric neuronal antibodies and no reactivity for the same autoantigens in samples not containing anti-enteric neuronal antibodies in our immunostaining assay. Antibodies in sera from IBS patients recognized only 3 antigens out of an 8,000 immunoprotein array. The 3 antigens were: (1) a nondescript ribonucleoprotein (RNP-complex); (2) small nuclear ribonuclear polypeptide A; and (3) Ro-5,200 kDa. CONCLUSIONS: Results of the present study suggest that symptoms in a subset of IBS patients might be a reflection of enteric neuronal damage or loss, caused by circulating anti-enteric autoimmune antibodies. PMID- 22323992 TI - Prevalence and predictive factors of fecal incontinence. AB - BACKGROUND/AIMS: Most previous epidemiologic studies about fecal incontinence were performed in specific populations in Korea. We aimed to estimate the prevalence and predictive factors of fecal incontinence in adult Korean population, both men and women aged 20 years and over. METHODS: Subjects who had undergone medical check-up for health screening were enrolled. They completed the structured questionnaires, including demographics, gastrointestinal symptoms, medical and social histories, and also about their bowel habits. Logistic regression models were constructed to identify the predictive factors for having fecal incontinence. RESULTS: Among the total of 1,149 subjects (mean age, 44.8 +/ 10.2 years; 648 males), the overall prevalence of fecal incontinence was 6.4%, while the older group (> 50 years old) showed the higher prevalence than the younger group (<= 50 years old) (10.4% vs 4.9%, P = 0.001) without gender difference. Most patients had mild fecal incontinence in 78.4%. By multivariate analysis, old ages (Odd ratio [OR], 3.1; 95% confidence interval [CI], 1.9-5.2; P < 0.001), watery stool (OR, 2.8; 95% CI, 1.5-4.9; P = 0.001) and functional diarrhea (OR, 2.7; 95% CI, 1.4-5.4; P = 0.004) were found to be independent predictors for fecal incontinence. CONCLUSIONS: The prevalence of fecal incontinence in Korean adults was 6.4%, and it was significantly more prevalent in older people without any gender difference. Aging and diarrhea were independent predictive factors of fecal incontinence. Therefore, proper control of the bowel pattern would lead to the prevention of fecal incontinence. PMID- 22323993 TI - How to interpret a functional or motility test - colon transit study. AB - Measurement of colon transit time is the most basic and primary tool in evaluating disorders of colonic motility. In particular, it is helpful in pathologic diagnosis and for planning management in patients with constipation. Several techniques for measuring colon transit time currently exist. The standard measurement of colon transit time has been performed using radioopaque marker test. The radioopaque marker test is the most widely used method; it is simple to perform as well as being cost effective. But, this technique produces radiation exposure. Radionuclide scintigraphy and wireless motility capsules are other techniques used to measure colon transit time. In radionuclide scintigraphy, the transit of radioisotope is viewed by gamma camera; this approach has an advantage in that it uses minimal radiation and it allows a physiological assessment of gastrointestinal transit. Wireless motility capsules have been validated most recently, but this technique is not useful in Korea. This review presents the techniques used to measure colon transit time and the interpretations provided in different colon transit studies. PMID- 22323994 TI - A patient with progression of diffuse esophageal spasm to classic achalasia. PMID- 22323995 TI - Variant achalasia: a new category of the chicago classification published in 2011. PMID- 22323996 TI - Dose Irritable Bowel Syndrome and Dysmotility Have an Autoimmune Origin? (Neurogastroenterol Motil 2011;23:1000-1006, e459). PMID- 22323997 TI - Acute tryptophan depletion and functional brain imaging in irritable bowel syndrome (gut 2011;60:1196-1203). PMID- 22323998 TI - Is otilonium bromide really effective for treating asian patients with irritable bowel syndrome? PMID- 22323999 TI - Is Otilonium Bromide Really Effective for Treating Asian Patients With Irritable Bowel Syndrome?: Author's Reply. PMID- 22324000 TI - The necessity of validated questionnaires: determining accurate responses to proton pump inhibitor use. PMID- 22324001 TI - What is the correct assignment on enrolled patients receiving various doses of medication in a study design? PMID- 22324002 TI - A new role for periodontists in the 21st century. PMID- 22324003 TI - A comprehensive review of techniques for biofunctionalization of titanium. AB - A number of surface modification techniques using immobilization of biofunctional molecules of Titanium (Ti) for dental implants as well as surface properties of Ti and Ti alloys have been developed. The method using passive surface oxide film on titanium takes advantage of the fact that the surface film on Ti consists mainly of amorphous or low-crystalline and non-stoichiometric TiO(2). In another method, the reconstruction of passive films, calcium phosphate naturally forms on Ti and its alloys, which is characteristic of Ti. A third method uses the surface active hydroxyl group. The oxide surface immediately reacts with water molecules and hydroxyl groups are formed. The hydroxyl groups dissociate in aqueous solutions and show acidic and basic properties. Several additional methods are also possible, including surface modification techniques, immobilization of poly(ethylene glycol), and immobilization of biomolecules such as bone morphogenetic protein, peptide, collagen, hydrogel, and gelatin. PMID- 22324004 TI - Analysis of the embrasure dimensions between maxillary central incisors in relation to the topography of the interdental papilla. AB - PURPOSE: To analyze the dimensions of the embrasure space between the maxillary central incisors as potential factors influencing interdental papilla fill and height. METHODS: The embrasure dimensions between the maxillary central incisors of 100 subjects (40 females/60 males) were assessed with clinical, study model, and radiographic examinations. Variables of the complete and deficient papilla fill groups were compared. Multiple regression analyses were performed to investigate potential influence of the distance between the contact point and bone crest (CP_BC), horizontal interdental distance (HID), and facio-lingual thickness (FLT) at the papilla base on complete/deficient papilla fill and papilla height (PH). RESULTS: CP_BC was the only variable that showed a significant difference between the complete and deficient papilla groups (P<0.05). When the CP_BC was less than 5 mm, the embrasure spaces between the maxillary central incisors were completely filled with interdental papilla. Multiple regression analyses revealed that a significant predictor for complete/deficient papilla fill was CP_BC, and significant predictors for PH were CP_BC and HID (P<0.05). CONCLUSIONS: The chances of complete papilla fill increased as CP_BC decreased, while PH increased as CP_BC and HID increased. However, the FLT of the papilla base did not appear to affect papilla fill or PH. From an esthetic perspective, CP_BC as well as HID should be considered as factors influencing the topography of interdental papilla. PMID- 22324005 TI - Profile of chronic and aggressive periodontitis among Senegalese. AB - PURPOSE: To describe the profile of chronic and aggressive periodontitis among Senegalese (West Africans) attending the Institute of Dentistry of Dakar. METHODS: A retrospective study was conducted with an inclusion period running from 2001 to 2008. The sample included 413 chronic periodontitis and 151 aggressive periodontitis cases, among them 299 males and 265 females selected from 2,274 records. A Student's independent t-test or Pearson chi-squared test was used for data analysis. RESULTS: The proportion of females with aggressive periodontitis was significantly higher than those with chronic periodontitis (64.9% vs. 40.4%, P<0.001). The aggressive periodontitis patients had an average age of 28.1+/-8.9 years, and had lost less than 3 teeth. Less than a third of them reported using a toothbrush. Attachment loss was as high as 8 mm and severe lesions had spread to an average of 12 teeth with maximum alveolar bone loss up to 80%. The chronic periodontitis patients had an average age of 44.9+/-14.0 and had lost on average less than 3 teeth. Nearly 75% used a toothbrush. Attachment loss was significantly higher and lesions were more extensive in the aggressive periodontitis. Chronic periodontitis is associated with risk factors such as smoking or diabetes mellitus in 12.8% versus 0.7% in aggressive periodontitis (P<0.001). Differences between the two groups for most clinical and radiographic parameters were statistically significant. CONCLUSIONS: The profile of aggressive periodontist is characterized by more severe lesions than chronic periodontitis, whereas tooth loss experience is similar in both forms. PMID- 22324006 TI - Periodontal regenerative effect of a bovine hydroxyapatite/collagen block in one wall intrabony defects in dogs: a histometric analysis. AB - PURPOSE: The aim of this study was to elucidate the effect of a bovine hydroxyapatite/collagen (BHC) block in one-wall intrabony periodontal defects in dogs. METHODS: A one-wall intrabony periodontal defect (4 mm wide and 5 mm deep) was prepared bilaterally at the mesial side of the mandibular fourth premolar in five beagle dogs. After thorough root planing, block-type BHC (4*5*5 mm) was placed on one side. The contralateral defect area did not receive any material as a sham-surgery control. Histological analysis of the sites was performed after an 8-week healing period. RESULTS: Two of five samples in the experimental group healed well without dissipation of the graft materials, and histological analysis revealed excellent regeneration of the periodontal tissues. However, most of the grafted materials had been displaced in the other three samples, leaving only a small portion of the graft. The measured parameters exhibited large standard deviations, and the mean values did not differ significantly between the experimental and sham-surgery control sides. CONCLUSIONS: The application of BHC alone-without a barrier membrane-to wide, one-wall intrabony periodontal defects yielded inconsistent results regarding both periodontal regeneration and substantivity of the graft materials. Thus, the use of a barrier membrane for noncontained-type defects is recommended to improve the stability of the grafted material, and to condense it. PMID- 22324007 TI - Comparative study on the cellular activities of osteoblast-like cells and new bone formation of anorganic bone mineral coated with tetra-cell adhesion molecules and synthetic cell binding peptide. AB - PURPOSE: We have previously reported that tetra-cell adhesion molecule (T-CAM) markedly enhanced the differentiation of osteoblast-like cells grown on anorganic bone mineral (ABM). T-CAM comprises recombinant peptides containing the Arg-Gly Asp (RGD) sequence in the tenth type III domain, Pro-His-Ser-Arg-Asn (PHSRN) sequence in the ninth type III domain of fibronectin (FN), and the Glu-Pro-Asp Ilu-Met (EPDIM) and Tyr-His (YH) sequence in the fourth fas-1 domain of betaig h3. Therefore, the purpose of this study was to evaluate the cellular activity of osteoblast-like cells and the new bone formation on ABM coated with T-CAM, while comparing the results with those of synthetic cell binding peptide (PepGen P-15). METHODS: To analyze the cell viability, 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay was performed, andto analyze gene expression, northernblot was performed. Mineral nodule formations were evaluated using alizarin red stain. The new bone formations of each group were evaluated using histologic observation and histomorphometrc analysis. RESULTS: Expression of alkaline phosphatase mRNA was similar in all groups on days 10 and 20. The highest expression of osteopontin mRNA was observed in the group cultured with ABM/P-15, followed by those with ABM/T-CAM and ABM on days 20 and 30. Little difference was seen in the level of expression of collagen type I mRNA on the ABM, ABM/T-CAM, and ABM/P-15 cultured on day 20. There were similar growth and proliferation patterns for the ABM/T-CAM and ABM/P-15. The halo of red stain consistent with Ca(2+) deposition was wider and denser around ABM/T-CAM and ABM/P 15 particles than around the ABM particles. The ABM/T-CAM group seemed to have bone forming bioactivity similar to that of ABM/P-15. A complete bony bridge was seen in two thirds of the defects in the ABM/T-CAM and ABM/P-15 groups. CONCLUSIONS: ABM/T-CAM, which seemed to have bone forming bioactivity similar to ABM/P-15, was considered to serve as effective tissue-engineered bone graft material. PMID- 22324008 TI - Gingival recontouring by provisional implant restoration for optimal emergence profile: report of two cases. AB - PURPOSE: The emergence profile concept of an implant restoration is one of the most important factors for the esthetics and health of peri-implant soft tissue. This paper reports on two cases of gingival recontouring by the fabrication of a provisional implant restoration to produce an optimal emergence profile of a definitive implant restoration. METHODS: After the second surgery, a preliminary impression was taken to make a soft tissue working cast. A provisional crown was fabricated on the model. The soft tissue around the implant fixture on the model was trimmed with a laboratory scalpel to produce the scalloped gingival form. Light curing composite resin was added to fill the space between the provisional crown base and trimmed gingiva. After 4 to 6 weeks, the final impression was taken to make a definitive implant restoration, where the soft tissue and tooth form were in harmony with the adjacent tooth. RESULTS: At the first insertion of the provisional restoration, gum bleaching revealed gingival pressure. Four to six weeks after placing the provisional restoration, the gum reformed with harmony between the peri-implant gingiva and adjacent dentition. CONCLUSIONS: Gingival recontouring with a provisional implant restoration is a non-surgical and non-procedure-sensitive method. The implant restoration with the optimal emergence profile is expected to provide superior esthetic and functional results. PMID- 22324009 TI - Clinicopathologic significance of gastric adenocarcinoma with neuroendocrine features. AB - PURPOSE: Composite neuroendocrine-exocrine carcinomas are malignancies that have two distinct components residing within the same tumor: an adenocarcinomatous portion and a neuroendocrine portion. This is rare in gastric cancers; however, poorly differentiated adenocarcinomas can sometimes reveal evidence of neuroendocrine features (NEF) or be 'mixed endocrine and exocrine carcinomas'. This study aimed to review NEF in gastric adenocarcinoma and to evaluate its prognostic significance. MATERIALS AND METHODS: We selected 29 patients who were diagnosed with gastric adenocarcinoma with NEF and received gastrectomies at the Department of Surgery, Ajou University Hospital between January 2001 and December 2009. We analyzed the clinicopathologic features of gastric cancer with NEF and the prognosis associated with such tumors. RESULTS: THE PATHOLOGIC RESULT WITH RESPECT TO TNM STAGING OF THE GASTRIC CANCERS WITH NEF WERE AS FOLLOWS: 5 cases of T1, 5 cases of T2, 10 cases of T3, and 9 cases of T4. There were 7 cases of N0, 7 cases of N1, 8 cases of N2 and 7 cases of N3. The staging of patients with NEF was higher than that of patients without NEF. Especially tumor lymphovascular invasion rate was 82.8%. The overall survival of patients with gastric cancer characterized by NEF was 73.8 months. CONCLUSIONS: Positive NEF status might be correlated with clinicopathologic parameters such as a high stage and high frequency of regional lymph node metastasis. PMID- 22324010 TI - Aging over 70 Years Is Not a Decisively Dismal Prognostic Factor in Gastric Cancer Surgery. AB - PURPOSE: Gastric cancer has a high incidence and mortality rate in Korea. Despite a growing older population and an increase in the number of older patients with gastric cancer, the older patients are not willing to undergo surgery due to their operative risks. Hence, to determine the clinical characteristics and outcomes of gastric cancer surgery for them, we investigate factors influencing the treatment decision. MATERIALS AND METHODS: Between January 1996 and December 2005, a total of 1,519 patients were classified into two groups; the younger age group between 41 and 69 years of age, and the older age group of 70 years or older. The analysis conducted included patient characteristics, accompanying disorders, related American Society of Anesthesiologists (ASA) grade, pathological characteristics and survival rate for each age group. RESULTS: Significant differences were found in the ASA grade (P<0.001) and the number of accompanying disorders (P<0.001) between the two groups. The average length of hospital stay after surgery was 14.5 days in the younger age group, and 13.3 days in the older age group (P=0.065). The average survival time was 47.5 months in the younger age group, and 43.2 months in the older age group (P<0.001). CONCLUSIONS: This study demonstrated that there was more number of accompanying disorders with a high surgical risk in the older age group. However, there was no significant difference between the older and younger age groups in terms of the incidence of complications, under the given disease conditions and if proper management was provided. PMID- 22324011 TI - Totally laparoscopic total gastrectomy using intracorporeally hand-sewn esophagojejunostomy. AB - PURPOSE: Laparoscopic total gastrectomy (LTG) for gastric cancer is still uncommon because of technical difficulties, especially in esophagojejunostomy (EJ). There are many reports for various laparoscopic procedures of EJ using linear or circular staplers. On the other hands, there has been no report for hand-sewn anastomosis. We report successfully performed intracorporeally hand sewn EJ after LTG. MATERIALS AND METHODS: The clinicopathologic data and short term surgical outcomes of 6 patients who underwent totally laparoscopic total gastrectomy for upper gastric cancer from December 2010 and July 2011 were retrospectively reviewed. RESULTS: The mean age was 66.5 years and mean body mass index (kg/m(2)) was 24.6. All patients had medical comorbidities. The mean patient ASA score was 2.17. Among the 6 patients, previous abdominal operation was performed for 2 patients and combined operation was performed for 3 patients. The mean blood loss, operation time, and EJ anastomosis time was 130 ml, 379.7 minutes, and 81.5 minutes, respectively. The mean time to first flatus, first oral intake, and postoperative hospital stay was 3.0, 3.0, and 12.5 days, respectively. There was no 30-day mortality case. Postoperative aspiration pneumonia and multiple periventricular lacunar infarctions developed in 1 patient. There were no anastomosis-related complications and other major surgical complications. CONCLUSIONS: When the intracorporeal anastomotic technique becomes popular in LTG the intracorporeally hand-sewn EJ may be accepted as one method among the various laparoscopic procedures of EJ. PMID- 22324012 TI - Intracorporeal Anastomosis Using Linear Stapler in Laparoscopic Distal Gastrectomy: Comparison between Gastroduodenostomy and Gastrojejunostomy. AB - PURPOSE: Intracorporeal anastomosis during laparoscopic gastrectomy is becoming increasingly prevalent. However, selection of the anastomosis method after laparoscopic distal gastrectomy is equivocal because of a lack of technical feasibility and safety. We compared intracorporeal gastroduodenostomy with gastrojejunostomy using linear staplers to evaluate the technical feasibility and safety of intracorporeal anastomoses as well as its' minimally invasiveness. MATERIALS AND METHODS: Retrospective analyses of a prospectively collected database for gastric cancer revealed 47 gastric cancer patients who underwent laparoscopic distal gastrectomy with either intracorporeal gastroduodenostomy or gastrojejunostomy from March 2011 to June 2011. Perioperative outcomes such as operation time, postoperative complication, and hospital stay were compared according to the type of anastomosis. Postoperative inflammatory response was also compared between the two groups using white blood cell count and high sensitivity C-reactive protein. RESULTS: Among the 47 patients, 26 patients received gastroduodenostomy, whereas 21 patients received gastrojejunostomy without open conversion or additional mini-laparotomy incision. There was no difference in mean operation time, blood loss, and length of postoperative hospital stays. There was no statistically significant difference in postoperative complication or mortality between two groups. However, significantly more staplers were used for gastroduodenostomy than for gastrojejunostomy (n=6) than for gastroduodenostomy and (n=5). CONCLUSIONS: Intracorporeal anastomosis during laparoscopic gastrectomy using linear stapler, either gastroduodenostomy or gastrojejunostomy, shows comparable and acceptable early postoperative outcomes and are safe and feasible. Therefore, surgeons may choose either anastomosis method as long as oncological safety is guaranteed. PMID- 22324013 TI - Efficacy of Roux-en-Y Reconstruction Using Two Circular Staplers after Subtotal Gastrectomy: Results from a Pilot Study Comparing with Billroth-I Reconstruction. AB - PURPOSE: The Roux en Y method has rarely been performed due to longer operation time and high risk of complication, despite several merits including prevention of bile reflux. We conducted a retrospective review of the result of Roux en Y reconstruction using two circular staplers after subtotal gastrectomy. MATERIALS AND METHODS: From December 2008 to May 2009, a total of 26 patients underwent Roux en Y reconstruction using two circular staplers after subtotal gastrectomy, and seventy-two patients underwent Billroth-I reconstruction. Roux en Y anastomosis was performed using two circular staplers without hand sewing anastomosis. We compared clinicopathologic features and surgical outcomes between the two groups. All patients underwent gastrofiberscopy between six and twelve months after surgery to compare the bile reflux. RESULTS: No significant differences in clinicopathologic findings were observed between the two groups, except for the rate of minimal invasive surgery (P=0.004) and cancer stage (P=0.002). No differences in the rate of morbidity (P=0.353) and admission duration (P=0.391) were observed between the two groups. Gastrofiberscopic findings showed a significant reduction of bile reflux in the remnant stomach in the Roux en Y group (P=0.019). CONCLUSIONS: When compared with Billroth-I reconstruction, Roux en Y reconstruction using the double stapler technique was found to reduce bile reflux in the remnant stomach without increasing postoperative morbidity. Based on these results, we planned to begin a randomized controlled clinical trial for comparison of Roux en Y reconstruction using this method with Billroth-I anastomosis. PMID- 22324014 TI - The single incision laparoscopic intragastric wedge resection of gastric submucosal tumor. AB - PURPOSE: Laparoscopic wedge resection of gastric submucosal tumor may be difficult in case of the endophytic mass or the mass located unreachable area such as cardia, and intragastric approach can be useful. We would present the experiences of the intragastric wedge resection. MATERIALS AND METHODS: There were 7 patients diagnosed as gastric submucosal tumor and underwent the intragastric wedge resection at Surgery, Chungnam National University Hospital. We reviewed medical record. RESULTS: There were 3 male and 4 female. Mean age was 65 years-old (57~73). Mean body mass index was 26.28 kg/m(2) (21.28~35.30). Location of lesions was 4 cardia, 2 fundus and 1 midbody, respectively. Mean operation time was 83.6 minutes (70~105). All patients were healed without any complication. Mean postoperative hospital stay was 5.4 days (4~6). Mean size was 2.7 cm (2.3~3.8). Pathologic finding was 5 gastrointestinal stromal tumor and 2 leiomyoma. CONCLUSIONS: The single incision intragastric wedge resection of gastric submucosal tumor is feasible and acceptable, especially in mass of gastric upper part. PMID- 22324015 TI - New surgical approach for gastric bezoar: "hybrid access surgery" combined intragastric and single port surgery. AB - Regarding the removal of a gastric bezoar, laparoscopic surgery was performed and it was shown that the laparoscopic approach is safe and feasible. However, the laparoscopic method has the risk of intraabdominal contamination, when the gastric bezoar is retrieved from the gastric lumen in the peritoneal cavity. We developed and applied a new procedure for the removal of the gastric bezoar using one surgical glove and two wound retractors as a fashion of intragastric single port surgery. Herein we present this new minimal invasive procedure, so named "hybrid access surgery" which involves the use of existing devices and overcomes the weakness of laparoscopic removal of the gastric bezoar. Our new procedure, combining the concept of intragastric and single port access, is acceptable and feasible to retrieve the gastric bezoar. In the future, this procedure may be one of the alternative procedures for retrieving gastric bezoar even when it is incarcerated in the pylorus. PMID- 22324016 TI - Neuroendocrine tumor of unknown primary accompanied with stomach adenocarcinoma. AB - A 67 year old male at a regular checkup underwent esophagogastroduodenoscopy. On performing esophagogastroduodenoscopy, a lesion about 1.2 cm depressed was noted at the gastric angle. The pathology of the biopsy specimen revealed a well differentiated adenocarcinoma. On performing an abdominal computed tomography (CT) scan & positron emission tomography-computed tomography (PET-CT) scan, no definite evidence of gastric wall thickening or mass lesion was found. However, lymph node enlargement was found in the left gastric and prepancreatic spaces. This patient underwent laparoscopic assisted distal gastrectomy and D2 lymph node dissection. On final examination, it was found out that the tumor had invaded the mucosal layer. The lymph node was a metastasized large cell neuroendocrine carcinoma with an unknown primary site. The patient refused chemotherapy. He opted to undergo a close follow-up. At the postoperative month 27, he had a focal hypermetabolic lesion in the left lobe of the liver that suggested metastasis on PET-CT scan. He refused to undergo an operation. He underwent a radiofrequency ablation. PMID- 22324017 TI - Totally laparoscopic resection for a large gastrointestinal stromal tumor of stomach. AB - A debate is currently ongoing about whether a large gastrointestinal stromal tumor (GIST) should be treated by the laparoscopic approach because of the increased risk of tumor rupture during manipulation of the tumor with laparoscopic instruments and the resultant peritoneal tumor dissemination. Herein, we report a case of a large GIST of the stomach which was successfully treated by the laparoscopic approach. A 57 year old female patient visited our institution complaining of postprandial epigastric discomfort. An esophagogastroduodenoscopy and an abdominal computed tomography scan revealed a 10*8 cm sized submucosal tumor at the greater curvature side of the gastric antrum. The patient underwent laparoscopic distal gastrectomy with intracorporeal Billroth-II reconstruction without any breakage of the tumor. Her postoperative course was uneventful and she was discharged on the 7th postoperative day. Even a large GIST of the stomach can safely be treated by the laparoscopic approach when it is performed with proper techniques by an experienced surgeon. PMID- 22324019 TI - Erratum to: Clinical Outcomes of Gastrectomy after Incomplete EMR/ESD. PMID- 22324018 TI - Giant mesenteric cystic lymphangioma originating from the lesser omentum in the abdominal cavity. AB - A 48 year old woman was diagnosed with a huge cystic mass in her abdominal cavity. She complained of significant abdominal discomfort due to the mass. The abdominal computed tomography revealed a giant multi-lobulated mass, measuring 26*12 cm in size, adjacent to the lesser curvature of the stomach. In the operation field, the mass was found to originate from the lesser omentum, including the right and left gastric vessels and the vagus nerves, and to invade the lesser curvature of the stomach. For curative resection, distal subtotal gastrectomy with mass excision followed by gastroduodenostomy were performed. This mass was pathologically diagnosed to be a mesenteric cystic lymphangioma; in fact, the largest ever reported. The patient had no complications during the postoperative period and was discharged from the hospital on the seventh day after surgery. PMID- 22324020 TI - Erratum to: Clinical Outcomes according to Primary Treatment in Gastric Cancer Patients with Peritoneal Seeding. PMID- 22324022 TI - Expression of matrix metalloproteinase-2 and -13 and tissue inhibitor of metalloproteinase-4 in varicose veins. AB - BACKGROUND: The relationship between the degree of expression of matrix metalloproteinases or tissue inhibitor of metalloproteinases and venous reflux remains to be investigated. MATERIALS AND METHODS: Primary varicose vein tissues were obtained from 23 patients, 18 females and 5 males, aged from 19 to 73. Cephalic or basilic veins were obtained for the control group from 10 patients who underwent vascular access for maintenance hemodialysis. Two operative techniques (high ligation with stripping or endovenous laser coagulation) were used. The expression of matrix metalloproteinase-2 and 13 and tissue inhibitor of metalloproteinase-4 in the varicose vein group and control group was assessed semi-quantitatively by immunohistochemical slides stained with primary antibodies. RESULTS: Twenty (87%) of the varicose vein group patients had greater or lesser saphenous vein diseases with reflux. The focal weak (+) stain for matrix metalloproteinases-2, and 13, and tissue inhibitor of matrix metalloproteinase-4 was dominant in the varicose vein group; the focal or diffuse strong stain (++ or +++) was prevalent in the control group. The differences were statistically significant (p<0.01). The degree of reflux and the duration of symptoms were not significantly related to the expression of MMP-13 (p=0.317 and p=0.654, respectively). CONCLUSION: Further study should be performed to investigate the relationship between the clinical characteristics related to venous hypertension or reflux and expression of MMPs and TIMP in varicose veins. PMID- 22324023 TI - Outcome of Staged Repair of Tetralogy of Fallot with Pulmonary Atresia and a Ductus-dependent Pulmonary Circulation: Should Primary Repair Be Considered? AB - BACKGROUND: The tetralogy of Fallot (TOF) with pulmonary atresia (PA) and a ductus-dependent pulmonary circulation (no major aorto-pulmonary collateral arteries (MAPCAs)) has been treated with staged repair or primary repair depending on the preference of surgeons or institutions. We evaluated the 19-year outcome of staged repair for this anomaly to find out whether our surgical strategy should be changed. MATERIALS AND METHODS: Forty-four patients with TOF/PA with patent ductus arteriosus (PDA) who underwent staged repair from June 1991 to October 2010 were included in this retrospective study. The patients with MAPCAs were excluded. The average age at the first palliative shunt surgery was 40.8+/-67.5 days (range: 0~332 days). Thirty-one patients (31/44, 70%) were neonates. The average weight was 3.5+/-1.6 kg (range: 1.6~8.7 kg). A modified Blalock-Taussig (BT) shunt was performed in 38 patients, classic BT shunt in 4 patients, and central shunt in 2 patients. Six patients required concomitant procedures: pulmonary artery angioplasty was performed in 4 patients, pulmonary artery reconstruction in one patient, and re-implantation of the left pulmonary artery to the main pulmonary artery in one patient. Four patients required a second shunt operation before the definitive repair was performed. Thirty-three patients underwent definitive repair at 24.2+/-13.3 months (range: 7.3~68 months) after the first palliative operation. The average age at the time of definitive repair was 25.4+/-13.5 months (range: 7.6~68.6 months) and their average weight was 11.0+/-2.1 kg. For definitive repair, 3 types of right ventricular outflow procedures were used: extra-cardiac conduit was performed in 30 patients, trans annular patch in 2 patients, and REV operation in 1 patient. One patient was lost to follow-up after hospital discharge. The mean follow-up duration for the rest of the patients was 72+/-37 months (range: 4~160 months). RESULTS: Ten patients (10/44, 22.7%) died before the definitive repair was performed. Four of them died during hospitalization after the shunt operation. Six deaths were thought to be shunt-related. The average time of shunt-related deaths after shunt procedures was 8.7 months (range: 2 days~25.3 months). There was no operative mortality after the definitive repair, but one patient died from dilated cardiomyopathy caused by myocarditis 8 years and 3 months after the definitive repair. Five-year and 10-year survival rates after the first palliative operation were 76.8% and 69.1%, respectively. CONCLUSION: There was a high overall mortality rate in staged repair for the patients with TOF/PA with PDA. Majority of deaths occurred before the definitive repair was performed. Therefore, primary repair or early second stage definitive repair should be considered to enhance the survival rate for patients with TOF/PA with PDA. PMID- 22324021 TI - A Guide to HIV-1 Reverse Transcriptase and Protease Sequencing for Drug Resistance Studies. PMID- 22324024 TI - Mass reduction and functional improvement of the left ventricle after aortic valve replacement for degenerative aortic stenosis. AB - BACKGROUND: Left ventricular (LV) hypertrophy caused by aortic valve stenosis (AS) leads to cardiovascular morbidity and mortality. We sought to determine whether aortic valve replacement (AVR) decreases LV mass and improves LV function. MATERIALS AND METHODS: Retrospective review for 358 consecutive patients, who underwent aortic valve replacement for degenerative AS between January 1995 and December 2008, was performed. There were 230 men and 128 women, and their age at operation was 63.2+/-10 years (30~85 years). RESULTS: There was no in-hospital mortality, and mean follow-up duration after discharge was 48.9 months (2~167 months). Immediate postoperative echocardiography revealed that LV mass index and mean gradient across the aortic valve decreased significantly (p<0.001), and LV mass continued to decrease during the follow-up period (p<0.001). LV ejection fraction (EF) temporarily decreased postoperatively (p<0.001), but LV function recovered immediately and continued to improve with a significant difference between preoperative and postoperative EF (p<0.001). There were 15 late deaths during the follow-up period, and overall survival at 5 and 10 years were 94% and 90%, respectively. On multivariable analysis, age at operation (p=0.008), concomitant coronary bypass surgery (p<0.003), lower preoperative LVEF (<40%) (p=0.0018), and higher EUROScore (>7) (p=0.045) were risk factors for late death. CONCLUSION: After AVR for degenerative AS, reduction of left ventricular mass and improvement of left ventricular function continue late after operation. PMID- 22324025 TI - Adventitial fibroblast abormality in thoracic aortic aneurysms and aortic dissections. AB - BACKGROUND: Development of thoracic aortic aneurysms and aortic dissections (TAAD) is attributed to unbearable wall tension superimposed on defective aortic wall integrity and impaired aortic repair mechanisms. Central to this repair mechanisms are well-balanced and adequately functional cellular components of the aortic wall, including endothelial cells, smooth muscle cells (SMCs), inflammatory cells, and adventitial fibroblasts. Adventitial fibroblasts naturally produce aortic extracellular matrix (ECM), and, when aortic wall is injured, they can be transformed into SMCs, which in turn are involved in aortic remodeling. We postulated the hypothesis that adventitial fibroblasts in patients with TAAD may have defects in ECM production and SMC transformation. MATERIALS AND METHODS: Adventitial fibroblasts were procured from the adventitial layer of fresh aortic tissues of patients with TAAD (Group I) and of multi-organ donors (Group II), and 4-passage cell culture was performed prior to the experiment. To assess ECM production, cells were treated with TNF-alpha (50 pM) and the expression of MMP-2 / MMP-3 was analyzed using western blot technique. To assess SMC transformation capacity, cells were treated with TGF-beta1 and expression of SM alpha-actin, SM-MHC, Ki-67 and SM calponin was evaluated using western blot technique. Fibroblasts were then treated with TGF-beta1 (10 pM) for up to 10 days with TGF-beta1 supplementation every 2 days, and the proportion of transformed SMC in the cell line was measured using immunofluorescence assay for fibroblast surface antigen every 2 days. RESULTS: MMP-3 expression was significantly lower in group I than in group II. TGF-beta1-stimulated adventitial fibroblasts in group I expressed less SM alpha-actin, SM-MHC, and Ki-67 than in group II. SM calponin expression was not different between the two groups. Presence of fibroblast was observed on immunofluorescence assay after more than 6 days of TGF beta1 treatment in group I, while most fibroblasts were transformed to SMC within 4 days in group II. CONCLUSION: ECM production and SMC transformation are compromised in adventitial fibroblasts from patients with TAAD. This result suggests that functional restoration of adventitial fibroblasts could well be a novel approach for the prevention and treatment of TAAD. PMID- 22324026 TI - Outcomes of Sleeve Lobectomy versus Pneumonectomy for Lung Cancer. AB - BACKGROUND: Sleeve lobectomy for lung cancer in close proximity to or involving the carina is widely accepted. Operative morbidity and mortality rates, recurrence, and survival rates have varied considerably across studies. MATERIALS AND METHODS: From March of 2005 to July of 2010, sleeve lobectomy was performed in 19 patients and pneumonectomy was performed in 20 patients. In this paper, the results of sleeve lobectomy and pneumonectomy for patients with lung cancer will be compared and evaluated. RESULTS: There were no postoperative complications in either group, but there was one mortality in the pneumonectomy group. There was better preservation of pulmonary function in the sleeve lobectomy group than the pneumonectomy group (p=0.066 in FVC, p=0.019 in FEV1). The 3-year survival rates were 46.7% in the sleeve lobectomy group and 54.5% in the pneumonectomy group (p=0.505). The 3-year disease-free survival rates were 38% in the sleeve lobectomy group and 45.8% in the pneumonectomy group (p=0.200). CONCLUSION: Sleeve lobectomy for lung cancer showed low mortality, low bronchial anastomotic complication rates, and good preservation of pulmonary function. PMID- 22324027 TI - Comparative study for the efficacy of small bore catheter in the patients with iatrogenic pneumothorax. AB - BACKGROUND: It has recently become most general to use the small bore catheter to perform closed thoracostomy in treating iatrogenic pneumothorax. This study was performed for analysis of the efficacy of treatment methods by using small bore catheter such as 7 F (French) central venous catheter, 10 F trocar catheter, 12 F pigtail catheter and for analysis of the appropriateness of each procedure. MATERIALS AND METHODS: From March 2007 to February 2010, Retrospective review of 105 patients with iatrogenic pneumothorax, who underwent closed thoracostomy by using small bore catheter, was performed. We analyzed the total success rate for all procedures as well as the individual success rate for each procedure, and analyzed the cause of failure, additional treatment method for failure, influential factors of treatment outcome, and complications. RESULTS: The most common causes of iatrogenic pneumothorax were presented as percutaneous needle aspiration(PCNA) in 48 cases (45.7%), and central venous catheterization in 26 cases (24.8%). The mean interval to thoracostomy after the procedure was measured as 5.2 hours (1~34 hours). Total success rate of thoracostomy was 78.1%. The success rate was not significantly difference by tube type, with 7 F central venous catheter as 80%, 10 F trocar catheter as 81.6%, and 12 F pigtail catheter as 71%. Twenty one out of 23 patients that had failed with small bore catheter treatment added large bore conventional thoracostomy, and another 2 patients received surgery. The causes for treatment failure were presented as continuous air leakage in 12 cases (52.2%) and tube malfunction in 7 cases (30%). The causes for failure did not present significant differences by tube type. Statistically significant factors affecting treatment performance were not discovered. CONCLUSION: Closed thoracostomy with small bore catheter proved to be effective for iatrogenic pneumothorax. The success rate was not difference for each type. However, it is important to select the appropriate catheter by considering the patient status, pneumothorax aspect, and medical personnel in the cardiothoracic surgery department of the relevant hospital. PMID- 22324028 TI - Myocardial revascularization in two patients associated with antiphospholipid syndrome: different pathogenic patterns and angiographic results. AB - We report on two women who underwent myocardial revascularization associated with antiphospholipid syndrome (APS) with different pathogenic patterns. The first woman presented with acute myocardial infarction, and preoperative angiograms demonstrated rapidly progressing coronary lesions, presumptive unstable plaque, and dissection. Operative findings, however, showed fresh thrombi in the coronary arteries, and she was diagnosed postoperatively as having APS. Her one-year angiogram demonstrated improved coronary lesions and a competitive flow pattern in the grafts. The second woman presented with unstable angina and had been treated for systemic lupus erythematosus and secondary APS for more than 14 years. She underwent myocardial revascularization due to accelerated coronary atherosclerosis. Her one-year angiogram demonstrated patent grafts. PMID- 22324029 TI - Thoracic endovascular repair for complicated type B acute aortic dissection with distal malperfusion. AB - Successful thoracic endovascular repair for complicated Stanford type B acute aortic dissection in two patients is herein reported. The true lumen flow was immediately restored following stent graft deployment in the descending thoracic aorta with subsequent resolution of the distal malperfusion syndrome. One patient is doing well more than 15 months after surgery and another patient who was treated more recently is also doing well 7 months postoperatively. PMID- 22324030 TI - Surgical correction of cor triatriatum associated with pulmonary artery thrombosis in an adult. AB - We herein present a case of a successful correction of cor triatriatum associated with thrombotic pulmonary hypertension diagnosed in an adult female patient. We confirmed diagnosis using transthoracic and transesophageal echocardiography in addition to cardiac computed tomography and magnetic resonance imaging. Surgical repair comprised excision of the fibromuscular membranous septum in the left atrium, patch closure of an atrial septal defect, and reconstruction of the pulmonary arteries with a vascular graft. Cor triatriatum complicated pulmonary thrombotic hypertension with atrial septal defect is amenable to surgical correction with satisfactory results. PMID- 22324031 TI - Lemierre syndrome. AB - Lemierre syndrome is caused by acute oropharyngeal infections with secondary septic thrombophlebitis of the internal jugular vein and is characterized by frequent metastatic infections. A 56-year-old man presented with severe reddish inflammatory swelling of the right cervical soft tissue. Thrombophlebitis in the right internal jugular vein and multiple pulmonary embolisms were identified on neck and chest computed tomography (CT). He was treated with antibiotics and heparin for 4 weeks and then discharged without other complications. PMID- 22324032 TI - Glomangiomyoma of the trachea. AB - A glomus tumor is an uncommon soft tissue tumor that is most commonly found in the subungual area and a glomus originating in the trachea is extremely rare. Histologically and ultrastructurally, these tumors have been divided into three subtypes: classic glomus tumors, glomangiomas, and glomangiomyomas. Glomangiomyomas account for less than 10% of all glomus tumors and are the least common type. We report a case of a 54-year-old man with glomangiomyoma of the trachea who presented with stridor. We treated the tumor by segmental resection and primary repair via a transcervical approach. PMID- 22324033 TI - Bronchial carcinoid tumor arising from an intralobar bronchopulmonary sequestration. AB - We report a rare case of a 38-year-old woman with a bronchial carcinoid tumor arising from an intralobar bronchopulmonary sequestration. The vascular supply to the sequestered left lower lobe originated from the descending thoracic aorta. A left lower lobe lobectomy was performed. The findings of the pathological examination revealed an atypical carcinoid tumor that was immunopositive for chromogranin and synaptophysin. At the 3-year follow-up examination, the patient was healthy. PMID- 22324034 TI - Diffuse Alveolar Hemorrhage in a 39-year-old Woman: Unusual Initial Presentation of Microscopic Polyangiitis. AB - Microscopic polyangiitis (MPA) is a necrotizing vasculitis involving the small vessels without granulomatous inflammation. Most MPA initially presents with renal involvement without pulmonary involvement. Isolated and initially presenting alveolar hemorrhage is very rare. The patient was a 39-year-old female with a progressive cough, dyspnea, and blood-tinged sputum for the previous 5 days. We determined that her condition was MPA though VATS lung biopsy and renal biopsy. After 2 months of steroid therapy, the chest lesions had improved. We report here a rare case of MPA with isolated and initial involvement of the lung with a review of the literature. PMID- 22324035 TI - Colon interposition in children after failed tracheoesophageal fistula repair. AB - The most common surgical procedure used to manage tracheoesophageal fistula is the primary anastomosis of the esophagus. However, in the case of failed anastomosis, replacing the esophagus with another organ is necessary. We performed two procedures of colon interposition after failure of tracheoesophageal fistula repair. In those cases, stomach replacement was not possible because of a failed Ivor Lewis operation in one case and duodenal atresia in the other. PMID- 22324036 TI - Congenital Intercostal Lung Herniation Combined with an Unusual Morgagni's Hernia. AB - A 70-year-old male visited urgent care due to coughing for 1 month and left chest pain. He had no history of trauma. The initial chest computed tomography (CT) showed the 7th left intercostal lung herniation. A follow-up CT showed an intercostal lung herniation combined with a bowl herniation, which had developed due to a Morgagni's hernia. An emergency operation was performed due to the incarceration of the bowl and lung. The primary repair of the diaphragm was performed and the direct approximation of the 7th intercostal space was determined. We concluded that the defect of the diaphragm and the intercostal muscle was a congenital lesion, and the recurrent coughing was the aggravating factor of herniation. PMID- 22324037 TI - Post-traumatic Intramuscular Hemangioma of the Chest Wall. AB - Intramuscular hemangioma originated in chest wall is a rare benign tumor, with no relevant reports in Korea. In most cases, the tumor is discovered before the age of 30 years and it is reported that trauma operates as the initiation factor. It is essential to concern the clinical suspicion and conduct a CT scan for diagnosis. The principle of treatment is surgical excision with clear resection margin. The authors of this study report a case of surgical excision for post traumatic intramuscular hemangioma of the chest wall with review of literature. PMID- 22324038 TI - Notice about article: Lee SJ, Shin JK, Kim DC, Kim JS, Kim JS, Chee HK, Song MG. Recent early operative outcomes of comprehensive aortic root & valve reconstruction (CARVAR) procedure. Korean J Thorac Cardiovasc Surg 2009;42:696 703. PMID- 22324039 TI - Hypertonic saline downregulate the production level of lipopolysaccharide-induced migration inhibitory factor in THP-1 cells. AB - PURPOSE: Macrophage migration inhibitory factor (MIF) may serve as a general marker for systemic inflammation in septic and nonseptic acute critical illness. Additionally, our previous experiment has demonstrated that immunosuppressant Prostaglandin E(2) (PGE(2)) lowered MIF levels and inhibited T-cells proliferation when compared to control levels. The addition of hypertonic saline (HTS) increased MIF production as compared with PGE(2)-stimulated T-cells in concordance with restore PGE(2)-suppressed T-cells proliferation. Generally, HTS has been well known for its anti-inflammatory effect so far. Therefore, the experiments were conducted to evaluate MIF after stimulating lipopolysaccharide (LPS) either in the presence or absence of HTS in monocyte, in response to early phase injury. METHODS: Human acute monocytic leukemic cell line (THP-1) cells were cultured in RPMI media, to a final concentration of 1 * 10(6) cells/mL. The effect of HTS on LPS-induced MIF was evaluated in monocyte with 1 ug/mL LPS. HTS at 10, 20 or 40 mmol/L above isotonicity was added. MIF concentrations of the supernatant were determined by enzyme-linked immunosorbent assay, and cell lysates were used for Western blots analysis to determine the MIF expression. RESULTS: MIF concentrations in the cell supernatant increased in LPS-induced cells compared to control cells. Also, levels of MIF protein expression were higher in LPS stimulating cells. However, the addition of HTS to LPS stimulated cell restored MIF concentrations and MIF expression. CONCLUSION: The role of HTS in maintaining physiological balance in human beings, at least in part, should be mediated through the MIF pathway. PMID- 22324040 TI - Change of inter-facility transfer pattern in a regional trauma system after designation of trauma centers. AB - PURPOSE: The Ministry of Health and Welfare recently designated 35 major trauma specified centers (MTSC). The purpose of this study is to determine changes in patient flow and designated hospitals, and to describe the role of the emergency medical information center (EMIC) in a regional trauma care system. METHODS: Data of trauma patient inter-facility transfer arrangement by one EMIC were reviewed for 2 months before and after the designation of MTSC. The data included success or failure rates of the arrangement, time used for arrangement, and inquiring and accepting facility. RESULTS: At pre- and post-designation study period, there were 540 and 433 trauma patient inter-facility transfers arranged by EMIC, respectively. The median time used for arrangement decreased from 9.3 to 7.7 minutes (P = 0.007). Arrangement failure rate was 3.5% and 2.5%, respectively, with no significant interval change (P = 0.377). The percentage of inquiring MTSC decreased from 49.1 to 36.9% (P < 0.001). The percentage of accepting MTSC increased from 20.2 to 37.4% (P < 0.001). CONCLUSION: With the designation of MTSC, EMIC could arrange inter-facility transfers more quickly. The hospitals wanted more trauma patients after the designation. There would be a concentration of trauma patients to MTSCs in our region. Further studies are needed for scientific evidence on patient outcome. PMID- 22324041 TI - Body size and thyroid nodules in healthy Korean population. AB - PURPOSE: Excess weight and obesity have been associated with numerous diseases including thyroid cancer, but the relationship has been weak. The objective of this study was to evaluate the relationship of body sizes on thyroid nodules in healthy Korean population. METHODS: A total of 7,763 persons who underwent a health examination in our health examination center were included in this study. The epidemiologic factors, body size and thyroid ultrasound results were reviewed. We investigated the effects of body size on the presence of thyroid nodules and malignancy. RESULTS: The incidence of thyroid nodules was 20.6%. In the group who were found to have thyroid nodules, mean height, weight and body surface area (BSA) were significantly smaller compared to the others. Especially, in the women, smaller height (less than 160 cm) and overweight (>= 60 kg) were identified as independent risk factors for the presence of thyroid nodules. The patients with body mass index (BMI) subgroups of normal or overweight had a tendency to have thyroid nodules more frequently. The detection rate of thyroid cancer was 0.47%. The patients with thyroid cancer tended to be smaller in height and BSA than the others. CONCLUSION: A higher frequency of thyroid nodules was associated with women and, older age. In women, there were significant correlations in height, weight and BMI subgroups to the presence of thyroid nodules. PMID- 22324042 TI - Early experience with diagnosis and management of eroded gastric bands. AB - PURPOSE: Band erosion is a well-known complication of laparoscopic adjustable gastric band placement. We gained experience with laparoscopic removal of an eroded gastric band. METHODS: We retrospectively reviewed the operative log of our obesity surgery unit to identify all operations performed for band erosion from March 2009 to May 2011. RESULTS: During the study period, a total of six of 96 patients (6.3%), five females and one male, were diagnosed with band erosion and underwent surgical removal of the band system. The median time interval from the initial gastric band placement to the diagnosis of band erosion was 8.5 months (range, 7 to 22 months), with most band erosion occurring within the first year (5/6, 83%). The median body mass index at band removal was 28.4 kg/m(2). Upper abdominal pain was the most common symptom (5/6, 83%), and other signs and symptoms were port site infection (3/6, 50%) and loss of restriction and weight regain (1/6, 17%). All eroded bands were removed using laparoscopy. Further complications after laparoscopic removal of the band system were observed in three cases. One patient showed multiple intra-abdominal abscesses requiring insertion of a pigtail catheter for drainage. The other two patients experienced sepsis with localized peritonitis, eventually requiring laparoscopic washout and drainage. CONCLUSION: Gastric band erosion requires the removal of the gastric band. Laparoscopic removal is technically achievable in the majority of patients with eroded gastric band. The method can be challenging, has potential postoperative complications (fistula, abscess), and should be attempted only by experienced surgeons. PMID- 22324043 TI - A practical approach for assessing chemosensitivity in colorectal cancer cell lines by comparative analysis of cell viability and thymidylate synthase mRNA expression. AB - PURPOSE: The purpose of this study is to suggest a probable problem in chemosensitivity tests performed in practice and to speculate on practicable measures for more accurate chemosensitivity evaluation. METHODS: Three colorectal cancer cells (RSC, RRC1, and RRC2) were treated with 5-fluorouracil (5-FU). Inhibition percentage (%inhibition) of cancer cells and relative quantitation of thymidylate synthase (TS) mRNA were measured on day 2, day 5 after replacement of 70% media on day 2, day 7, and day 3 after replacement of all media on day 7. Doses that produced 50% inhibition (Dm) were calculated to evaluate drug effect. Relative quantitation of TS mRNA and correlations between TS mRNA levels and 5-FU concentrations were analyzed. RESULTS: RRC1 was more resistant than RRC2 on day 7, but Dm value of RRC2 increased three days after replacement of media from 12.3 to 18.1. Mean TS mRNA levels of RSC on D2 and D7 were significantly lower than those of RRC1 and RRC2, respectively (P = 0.004, P = 0.004 on D2; P = 0.010, P = 0.006 on D7). TS mRNA levels in RRC1 were significantly reversely correlated with 5-FU concentrations on day 2 (correlation coefficient = -0.867, P = 0.015). On the other hand, correlations were not significant in RRC2 (r = 0.067). CONCLUSION: Evaluating %inhibition of cancer cells at one point in chemosensitivity tests seems to be inadequate in determining chemotherapeutic regimens. Multilateral approaches, such as trials evaluating cancer cell survival before and after media replacement and correlations between TS mRNA levels and 5 FU concentrations, needs to be implemented for the practical application of chemosensitivity tests. PMID- 22324044 TI - Comparison of surgical-site infection between open and laparoscopic appendectomy. AB - PURPOSE: An inflamed appendix can be removed either openly (open appendectomy [OA]) or laparoscopically (laparoscopic appendectomy [LA]). Surgical-site infection (SSI) is a representative healthcare-associated infection and can impose serious economic burdens on patients as well as affect morbidity and mortality rates. The aim of this study was to compare LA with OA in terms of SSI. METHODS: The medical records of 749 patients (420 males; mean age, 33 years) who underwent appendectomy (OA, 431; LA, 318) between September 1, 2008 and April 29, 2010 were retrospectively reviewed for demographic and pathologic characteristics, recovery of bowel movement, length of hospital stay, and postoperative complications. RESULTS: The frequency of purulent/gangrenous or perforated appendicitis was not significantly different between LA and OA groups (83% [263/318 cases] vs. 83% [359/431 cases], P = 0.183). The time to first flatus after surgery was not significantly different between the two groups (1.38 +/- 1.07 days for LA, 1.33 +/- 0.90 days for OA, P = 0.444), but the length of hospital stay was significantly shorter in LA group than in OA group (3.37 +/- 0.12 days vs. 3.83 +/- 0.12 days, P = 0.006). The frequency of overall SSI was not significantly different between the two groups (2.8% for LA, 4.6% for OA, P = 0.204), but that of superficial incisional SSI was significantly lower in LA group (0.6% vs. 3.9%, P = 0.016). CONCLUSION: The results of this study suggest that LA may lead to a shorter length of hospital stay and may have a lower risk of superficial incisional SSI than OA. PMID- 22324045 TI - Comparison of the outcomes between laparoscopic totally extraperitoneal repair and prolene hernia system for inguinal hernia; review of one surgeon's experience. AB - PURPOSE: To compare the outcomes between laparoscopic total extraperitoneal (TEP) repair and prolene hernia system (PHS) repair for inguinal hernia. METHODS: A retrospective analysis of 237 patients scheduled for laparoscopic TEP or PHS repair of groin hernia from 2005 to 2009 was performed. RESULTS: The mean age was 52.3 years in TEP group and 55.7 years in PHS group. Of 119 TEP cases, 98 were indirect inguinal hernia, 15 direct type, 5 femoral hernia and 1 complex hernia; Of 118 PHS cases, 100 indirect, 18 direct type. All in TEP group were performed under general anesthesia and 64% of PHS group were performed under spinal or epidural anesthesia. Preoperatively, 10 cases of recurrent inguinal hernia were involved in our study (4 in TEP, 6 in PHS group). The mean operative time was similar in both groups (74.8 in TEP, 71.2 in PHS group), however mean hospital stay (1.6 days in TEP, 3.2 days in PHS group, P = 0.018) and mean usage of analgesics (0.54 times in TEP, 2.03 times in PHS group, P < 0.01), complications (36 cases in TEP, 6 cases in PHS group, P < 0.01) showed statistical differences. There is only 1 case of postoperative recurrence inguinal hernia in PHS group but it has no statistical significance (P = 0.314). CONCLUSION: Compared to PHS repair, laparoscopic TEP repair has some advantages; shorter hospital stay, less frequent need of analgesics; as well as more postoperative complications such as hematoma, seroma, scrotal swelling. PMID- 22324046 TI - Inflammatory myofibroblastic tumor in colon. AB - Inflammatory myofibroblastic tumor (IMT) is an uncommon mesenchymal solid tumor commonly documented in children and young adults. Here, we report a case of IMT in colon confirmed pathologically after laparoscopic anterior resection. A 35 year-old man presented with anal bleeding after defecation for 2 weeks. Colonoscopy demonstrated a mass with shallow ulceration in the central area and irregular margin accompanied by intact mucosa in the descending colon. Computer tomography showed a well-demarcated and homogenous solitary mass in the descending colon. We performed laparoscopic anterior resection. This case was diagnosed as IMT after microscopic examination. The tumor was composed of a proliferation of spindle-shaped cells arranged in the hyaline material with chronic inflammatory cells, composed mainly of plasma cells and lymphocytes. Immunohistochemically, tumor cells were positive for smooth muscle actin, and vimentin, and negative for desmin, CD117 (c-kit), anaplastic lymphoma kinase-1. PMID- 22324047 TI - Post-transplant lymphoproliferative disorder presented as small bowel intussusception in adult liver transplant patient. AB - Intestinal obstruction after liver transplant is a rare complication, with diverse clinical manifestations. Intestinal adhesion is the most common cause. However, internal hernia, abdominal wall hernia, and neoplasm are also reported. Intussusception is another rare cause of intestinal obstruction, which has been reported primarily in pediatric patients. Herein, we report a case of intestinal obstruction from intussusception in an adult liver transplant patient associated with post-transplant lymphoproliferative disorder. PMID- 22324048 TI - Primary carcinosarcoma of the gallbladder. AB - Carcinosarcoma of gallbladder (CSGB) is a rare malignancy characterized by malignant epithelial and mesenchymal components. Its pathogenesis is unknown and most CSGBs are associated with poor survival because the disease normally presents at an advanced stage, and as a result, curative resection is uncommon. This report describes a case that underwent curative resection. A 77-year-old woman presented with right upper quadrant pain. The preoperative diagnosis was gallbladder (GB) cancer, and thus, curative radical cholecystectomy was performed. However, pathologic examination of the surgical specimen revealed that the tumor was composed of two histologic components of squamous cell carcinoma and spindle cell sarcoma, which was consistent with a diagnosis of carcinosarcoma. The tumor was found to extend to the perimuscular connective tissue and to have metastasized to one lymph node (LN). The prognosis of CSGB remains poor despite curative resection, and thus, the authors recommend that effort be made to improve surgical outcomes. PMID- 22324049 TI - Successful treatment of type I endoleak of common iliac artery with balloon expandable stent (Palmaz XL stent) during endovascular aneurysm repair. AB - Type 1 endoleak of common iliac artery (type I(b) endoleak) should be treated during endovascular aneurysm repair (EVAR). An 86-year-old female was diagnosed with abdominal aortic aneurysm measuring 6.6 cm in diameter and right internal iliac artery aneurysm measuring 4.0 cm in diameter. She underwent EVAR after right internal iliac artery embolization. There was type I(b) endoleak, which was repaired by balloon-expandable stent, Palmaz XL stent (Cordis). We report successful treatment of type I(b) endoleak with Palmaz XL stent, which may be considered as an alternative option for type I(b) endoleak after EVAR. PMID- 22324050 TI - A chloride ion nanosensor for time-resolved fluorimetry and fluorescence lifetime imaging. AB - In this work, the first CdSe/ZnS quantum dot (QD) photoluminescence lifetime based chloride ion nanosensor is reported. The acridinium dication lucigenin was self-assembled on the surface of negatively charged mercaptopropionic acid capped QDs to achieve QD-lucigenin conjugates. Upon attachment, a drastic decrease of the photoluminescence lifetime of both QD nanoparticles and lucigenin is observed by virtue of a charge transfer mechanism. Since lucigenin is a chloride-sensitive indicator dye, the photoluminescence decay of QD-lucigenin conjugates changes by adding chloride ion. The photoluminescence lifetime of the QDs in the conjugate increases after reacting with Cl(-), but also shows a concomitant decrease in the lucigenin lifetime immobilized on the surface. The photoluminescence lifetime of QD-lucigenin nanosensors shows a linear response in the Cl(-) concentration range between 0.5 and 50 mM. Moreover, the ratio tau(ave)(QD)/tau(ave)(luc) can be used as an analytical signal since the lifetime ratio presents a linear response in the same Cl(-) concentration range. The system also shows good selectivity towards most of the main anions and molecules that can be found in biological fluids. These nanosensors have been satisfactorily applied for Cl(-) determination in simulated intracellular media with high sensitivity and high selectivity. Finally, we demonstrate the potential application of the proposed nanosensor in confocal fluorescence lifetime imaging (FLIM). These results show the promising application of the QD-lucigenin nanosensors in FLIM, particularly for intracellular sensing, with the invaluable advantages of the time-resolved fluorescence techniques. PMID- 22324051 TI - Separation of bacteria with imprinted polymeric films. AB - Separation of compounds out of complex mixtures is a key issue that has been solved for small molecules by chromatography. However, general methods for the separation of large bio-particles, such as cells, are still challenging. We demonstrate integration of imprinted polymeric films (IPF) into a microfluidic chip, which preferentially capture cells matching an imprint template, and separate strains of cyanobacteria with 80-90% efficiency, despite a minimal difference in morphology and fluorescence, demonstrating its general nature. It is currently thought that the imprinting process, conducted while the polymer cures, transfers chemical information of the cell's external structure to the substrate. Capture specificity and separation can be further enhanced by orienting the imprints parallel to the flow vector and tuning the pH to a lower range. PMID- 22324052 TI - Glanzmann thrombasthenia in pregnancy: the value of a probing bleeding history. PMID- 22324053 TI - Fibrinogen, hematocrit, and platelets in mild kidney dysfunction and the role of uric acid: an Italian male population study. PMID- 22324054 TI - Reliability of real-time ultrasound for measuring skeletal muscle size in human limbs in vivo: a systematic review. AB - OBJECTIVE: To systematically review evidence for the reliability of real-time brightness-mode ultrasound for assessing skeletal muscle size in human limbs in vivo and to establish in which populations and anatomical sites the reliability had been tested. DATA SOURCES: Articles were retrieved via electronic database searching and expert contact. STUDY SELECTION: Studies reporting reliability indices of test-retest measures of real-time brightness-mode ultrasound measures of skeletal muscle size within human limbs were included. DATA EXTRACTION: Articles were assessed for methodological quality by two reviewers, decisions were made by consensus. Participant characteristics, measurement protocol, ultrasound protocol, type of reliability measured and statistical methods were extracted by one reviewer. DATA SYNTHESIS: Twenty-four articles were included, involving 605 participants. Studies were of low to moderate methodological quality. Most studies were conducted within the healthy population. Only one study demonstrated poor reliability at one site only, and only when the participants were measured in the supine position. CONCLUSION: There is a moderate amount of low-level evidence that real-time brightness-mode ultrasound has good reliability for measuring muscle size across a number of limb sites in healthy populations. There is limited evidence for the reliability of ultrasound measures of muscle size in clinical populations. PMID- 22324055 TI - Wii Fit(r) training vs. Adapted Physical Activities: which one is the most appropriate to improve the balance of independent senior subjects? A randomized controlled study. AB - OBJECTIVE: To compare the effectiveness of three protocols (Adapted Physical Activities, Wii Fit((r)), Adapted Physical Activities + Wii Fit((r))) on the balance of independent senior subjects. DESIGN: Case comparison study. SETTINGS: Healthy elderly subjects living in independent community dwellings. SUBJECTS: Thirty-six subjects, average age 75.09 +/- 10.26 years, took part in this study, and were randomly assigned to one of the four experimental groups: G1 followed an Adapted Physical Activities training programme, while the second group (G2) participated in Wii Fit((r)) training and the third one (G3) combined both methods. There was no training for the fourth group (G4). All subjects trained once a week (1 hour) for 20 weeks and were assessed before and after treatment. MAIN MEASURES: The Tinetti test, unipedal tests and the Wii Fit((r)) tests. RESULTS: After training, the scores in the Tinetti test decreased significantly (P < 0.05) for G1, G2 and G3 respectively in static conditions and for G1 and G3 in dynamic conditions. After training, the performance in the unipedal tests decreased significantly (P < 0.05) for G1 and G3. The position of the centre of gravity was modified significantly (P < 0.05) for G2 and G3. CONCLUSION: After 20 training sessions, G1 (Adapted Physical Activities), G2 (Wii Fit((r))) and G3 (Adapted Physical Activities and Wii Fit((r))) improved their balance. In addition, G1 and G3 increased their dynamic balance. The findings suggest that Adapted Physical Activities training limits the decline in sensorial functions in the elderly. PMID- 22324056 TI - Evaluation of rehabilitation of memory in neurological disabilities (ReMiND): a randomized controlled trial. AB - OBJECTIVE: The evidence for the effectiveness of memory rehabilitation is inconclusive. The aim was to compare the effectiveness of two group memory rehabilitation programmes with a self-help group control. DESIGN: Single-blind randomized controlled trial. PARTICIPANTS: Participants with memory problems following traumatic brain injury, stroke or multiple sclerosis were recruited from community settings. INTERVENTIONS: Participants were randomly allocated, in cohorts of four, to compensation or restitution group treatment programmes or a self-help group control. All programmes were manual-based and comprised two individual and ten weekly group sessions. MAIN MEASURES: Memory functions, mood, and activities of daily living were assessed at baseline and five and seven months after randomization. RESULTS: There were 72 participants (mean age 47.7, SD 10.2 years; 32 men). There was no significant effect of treatment on the Everyday Memory Questionnaire (P = 0.97). At seven months the mean scores were comparable (restitution 36.6, compensation 41.0, self-help 44.1). However, there was a significant difference between groups on the Internal Memory Aids Questionnaire (P = 0.002). The compensation and restitution groups each used significantly more internal memory aids than the self-help group (P < 0.01). There were no statistically significant differences between the groups on measures of mood, adjustment and activities of daily living (P > 0.05). CONCLUSIONS: There results show few statistically significant effects of either compensation or restitution memory group treatment as compared with a self-help group control. Further randomized trials of memory rehabilitation are needed. PMID- 22324057 TI - An investigation of the validity of six measures of physical function in people awaiting joint replacement surgery of the hip or knee. AB - OBJECTIVE: To assess and compare the validity of six physical function measures in people awaiting hip or knee joint replacement. DESIGN: Eighty-two people awaiting hip or knee replacement were assessed using six physical function measures including the WOMAC Function scale, SF-36 Physical Function scale, SF-36 Physical Component Summary scale, Patient Specific Functional Scale, 30-second chair stand test, and 50-foot timed walk. Validity was assessed using a head-to head comparison design. RESULTS: Convergent validity was demonstrated with significant correlations between most measures (Spearman's rho 0.22 to 0.71). The Patient Specific Functional Scale had the lowest correlations with other measures of physical function. Discriminant validity was demonstrated with low correlations between mental health and physical function scores (Spearman's rho 0.12 to 0.33). Only the WOMAC Function scale, 30-second chair stand test, and 50 foot timed walk demonstrated known groups validity when scores for participants who walked with a gait aid were compared with those who did not. Standardized response means and Guyatt's responsiveness indexes indicated that the SF-36 was the least responsive measure. CONCLUSIONS: For those awaiting joint replacement surgery of the hip or knee, the current investigation found that the WOMAC Function scale, 30-second chair stand test, and 50-foot timed walk demonstrated the most evidence of validity. The Patient Specific Functional Scale might complement other measures by capturing a different aspect of physical function. PMID- 22324058 TI - Whole-body vibration in addition to strength and balance exercise for falls related functional mobility of frail older adults: a single-blind randomized controlled trial. AB - OBJECTIVES: To investigate the effects of whole-body vibration in addition to an exercise programme on functional mobility and related outcomes for frail older fallers. DESIGN: Single-blind randomized parallel group trial. SETTING: UK; National Health Service assessment and rehabilitation facility for older people. PARTICIPANTS: Frail older fallers: 38 (80 +/- 8.6 years) performed the exercise with whole-body vibration (vibration group), and 39 (82 +/- 8.1 years) without (exercise group). INTERVENTION: Sixty minutes supervised exercise class three times weekly for eight weeks +/- whole-body vibration (up to 5 * 1 minute, 15-30 Hz and 2-8 mm peak-to-peak). MEASUREMENTS: Timed Up and Go, 6-m walk, static balance, fear of falling (FES-I) and self-reported health status (SF-12 version 2) were assessed at baseline, four weeks (mobility measures only), eight weeks and six months. RESULTS: Timed Up and Go and 6-m walk improved in both groups at eight weeks (P < 0.01), but significantly more in the vibration group (timed up and go: 38 vs. 20%, P < 0.05); 6-m walk: (36 vs. 18.1%, P < 0.05, respectively). Balance, fear of falling and physical component of the self-reported health status improved similarly in both groups (P < 0.05). At follow-up, no significant differences from baseline remained for any measure. The mean total time experienced was 37% of maximal target. CONCLUSION: The addition of whole-body vibration to strength and balance exercise resulted in greater improvements in functional mobility than exercise alone, despite achieving lower than anticipated exposure. Gains from neither intervention were sustained at six months. PMID- 22324059 TI - Neuromuscular electrical stimulation in the treatment of knee osteoarthritis: a systematic review and meta-analysis. AB - OBJECTIVE: To assess the effectiveness of surface neuromuscular electrical stimulation in the treatment of knee osteoarthritis. DESIGN: Systematic review and meta-analysis of randomized controlled and controlled clinical trials METHODS: Studies were identified from databases (MEDLINE, EMBASE, CINAHL, Sports Discus, PEDro and the Cochrane Library) searched to January 2011 using a battery of keywords. Two reviewers selected studies meeting inclusion criteria. The methodological quality of the included studies was assessed using the Thomas Test and the strength of the evidence was then graded using the Agency for Health Care Policy and Research guidelines. Data were pooled and meta-analyses were performed. RESULTS: Nine randomized controlled trials and one controlled clinical trial, studying a total of 409 participants (n = 395 for randomized controlled trials, and n = 14 for controlled trial) with a diagnosis of osteoarthritis were included. Inconsistent evidence (level D) was found that neuromuscular electrical stimulation has a significant impact on measures of pain, function and quadriceps femoris muscle strength in knee osteoarthritis. CONCLUSION: The role of neuromuscular electrical stimulation in the treatment of knee osteoarthritis is ambiguous. Therefore, future work is needed in this field to clearly establish the role of neuromuscular electrical stimulation in this population. PMID- 20029611 TI - Adjuvant is necessary for a robust immune response to a single dose of H1N1 pandemic flu vaccine in mice. AB - Pandemic H1N1 influenza vaccine antigens are currently being manufactured. The MF59 adjuvant has an established safety profile in humans and a proven ability to increase responses to some influenza vaccines in humans. To inform initial decisions on the use of these vaccine components to protect human populations, we have immunized mice with MF59-adjuvanted or non-adjuvanted pandemic influenza vaccine. Immunizing unprimed mice with a single dose of MF59-adjuvanted vaccine elicits functional antibody titers equivalent to those associated with protection of humans from seasonal influenza. Without adjuvant, two doses are required for a robust antibody response. Unadjuvanted vaccines with 0.5 and 1 microgram of antigen elicit equivalent titers. These data support including MF59 in pandemic flu vaccines to rapidly protect young adults and children, who may have little or no previous exposure to influenza infection or immunization. PMID- 20029614 TI - The severity of pandemic H1N1 influenza in the United States, April - July 2009. AB - BackgroundAccurate measures of the severity of pandemic influenza A/H1N1 (pH1N1) are needed to assess the likely impact of an anticipated resurgence in the autumn in the Northern Hemisphere. Severity has been difficult to measure because jurisdictions with large numbers of deaths and other severe outcomes have had too many cases to assess the total number with confidence. Also, detection of severe cases may be more likely. Methods and FindingsWe used complementary data from two US cities: Milwaukee attempted to identify cases of medically attended infection whether or not they required hospitalization, while New York City focused on the identification of hospitalizations, intensive care admission or mechanical ventilation (hereafter, ICU), and deaths. New York data were used to estimate numerators for ICU and death, and two sources of data: medically attended cases in Milwaukee or self-reported influenza-like illness in New York, were used to estimate ratios of symptomatic cases:hospitalizations. Combining these data with estimates of the fraction detected for each level of severity, we estimated the proportion of symptomatic cases that died (symptomatic case-fatality ratio, sCFR), required ICU (sCIR), and required hospitalization (sCHR), overall and by age category. Evidence, prior information and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated sCFR of 0.045% (95% credible interval, CI 0.020%-0.090%), sCIR of 0.222% (0.105%-0.425%), and sCHR of 1.37% (0.68%-2.52%). Using self-reported ILI, we obtained estimates approximately 6-9x lower. sCFR was highest in the 18-64 age group, and sCIR and sCHR highest in the 18-64 or 0-4 age group depending on the approach. ConclusionsThese estimates suggest that an autumn-winter pandemic wave of pH1N1 with comparable severity per case could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, but with greatest impact in young children and non-elderly adults. These estimates of impact depend on assumptions about total incidence of infection in the autumn-winter. Impacts would larger if autumn-winter incidence of symptomatic infection were higher or shifted toward adults, if viral virulence increased, or if suboptimal treatment resulted from stress on the health care system; numbers would decrease if the proportion infected or symptomatic were lower. PMID- 22324062 TI - The general NFP hospital model. AB - Throughout the past 30 years, there has been a lot of controversy surrounding the proliferation of new forms of health care delivery organizations that challenge and compete with general NFP community hospitals. Traditionally, the health care system in the United States has been dominated by general NFP (NFP) voluntary hospitals. With the number of for-profit general hospitals, physician-owned specialty hospitals, and ambulatory surgical centers increasing, a question arises: "Why is the general NFP community hospital the dominant model?" In order to address this question, this paper reexamines the history of the hospital industry. By understanding how the "general NFP hospital" model emerged and dominated, we attempt to explain the current dominance of general NFP hospitals in the ever changing hospital industry in the United States. PMID- 22324063 TI - Game-changer for cataract surgery. Femtosecond lasers enable more efficient, faster, and safer cataract surgery, and are expected to be the standard of care within about five years. PMID- 22324064 TI - Knee osteoarthritis on the rise, but prevention & relief is possible. OA now occurs about 16 years earlier in life compared to 20 years ago. Exercise and weight loss can help relieve pain. PMID- 22324065 TI - Dietary supplements: not for everyone. New findings indicate supplements may actually harm some people. Getting nutrients from real food is best. PMID- 22324066 TI - Gentler method of restoring normal heart rhythm. High-frequency, alternating current could replace painful defibrillator shocks. PMID- 22324067 TI - Gene variation may predict rate of age-related cognitive decline. Research shows this key gene produces a protein associated with healthy brain function. PMID- 22324068 TI - My husband suffers from diverticulitis. Are there any dietary steps he can take to ease his symptoms? PMID- 22324069 TI - Does rheumatoid arthritis have any impact on the rest of the body? PMID- 22324070 TI - I recently heard that there are alternative medications to the blood thinner warfarin. What are they, and how are they different? PMID- 22324071 TI - Epidemiological analysis of health situation development in Europe and its causes until 1990. AB - The enormous health gap between the 'new' (eastern) and 'old' (western) parts of the EU has evolved over many decades. The epidemiological transition - that is the decrease in the relative importance of infant and early child mortality and the shift in the composition of mortality risks from communicable to non communicable diseases - which started in the western part of the region at the beginning of the 20th century, was substantially delayed in most of eastern Europe. However, after the World War II, health improvement in the east initially out-paced the west, such that, by the mid-1960s, only 1-2 years separated the average life expectancy for both sexes between the east and west. This convergence was short-lived and it reversed dramatically between the mid 1960s and 1990. During this period, adult health status in the east stagnated or deteriorated, whereas in the west it improved steadily: by 1990, life expectancy at the age of 20 years was more than fi ve years shorter in the east for men, and more than four years shorter for women. The biggest contributors to the health gap were cardiovascular diseases and injuries. A substantial fraction of the gap can, with confidence, be attributed to the higher volume and more irregular pattern of alcohol consumption in the east, and to the delayed onset of the tobacco smoking epidemics. Much of the remainder of the gap is likely to be attributable to the composition of the diet, but the contribution of different dietary factors cannot be estimated with confidence. Leading candidates are a high consumption of saturated animal fats, a low consumption of fresh fruit and vegetables (especially in winter and spring), a very low consumption of fats supplying omega 3 fatty acids - both vegetable oils and fi sh oils rich in alpha linolenic acid - and a high consumption of salt. Behaviours unfavourable to health did not change in the east, as they did in the west in response to the credible dissemination of scientific findings linking disease and injury risks both to individual behaviours and to the social and economic circumstances that fostered those behaviours. The eastern countries failed to equip themselves with the science and with the forms of social organisation that were needed to effectively counter epidemics of chronic disease and injury. The poor health related behavioural determinants resulted from the institutional infrastructures based on an authoritarian, conservative and medicalised model of health, which inhibited modern approaches to social problems, an almost exclusive focus of epidemiology on communicable as opposed to non-communicable diseases, a lack of understanding and access to modern epidemiology and public health, a lack of understanding and access to evidence-based medicine, and a lack of public health education and health promotion. PMID- 22324072 TI - POlish-Norwegian Study (PONS): research on chronic non-communicable diseases in European high risk countries - study design. AB - OBJECTIVE: A large-scale population study of health and disease would represent the most powerful tool to address these important issues in Poland. The aim is to extensively survey the study population with respect to important factors related to health and wellbeing, and subsequently, the intention is to follow-up the population for important health outcomes, including the incidence and mortality of cancer, cardiovascular disease, and other major causes of morbidity and mortality. The infrastructure for establishing a large cohort of people in Poland is needed; therefore, the PONS (Polish-Norwegian Study) project represents an eff ort to establish such infrastructure. METHODS: The PONS Study is enrolling individuals aged 45-64 years. Structured lifestyle and food frequency questionnaires are administered. Study participants undergo medical check-up, anthropometric measurements and provide blood and urine sample for long-term storage. Fasting glucose and lipids profile are checked in the laboratory. RESULTS: This report describes the design, justification and methodology of the presented prospective cohort study. Recruitment of participants began in September 2010, and by the end of 2011 it is planned to achieve a total of between 10,000 - 15,000 participants. SUMMARY: The PONS study is the fi rst prospective cohort study with blood and urine collection ever conducted in Central and Eastern Europe. It will provide reliable new data on both established and emerging risk factors for several major chronic diseases in a range of different circumstances. PMID- 22324073 TI - Tacaribe virus, a new agent isolated from Artibeus bats and mosquitoes in Trinidad, West Indies. PMID- 22324074 TI - In praise of counter-conduct. AB - Without access to Michel Foucault's courses, it was extremely difficult to understand his reorientation from an analysis of the strategies and tactics of power immanent in the modern discourse on sexuality (1976) to an analysis of the ancient forms and modalities of relation to oneself by which one constituted oneself as a moral subject of sexual conduct (1984). In short, Foucault's passage from the political to the ethical dimension of sexuality seemed sudden and inexplicable. Moreover, it was clear from his published essays and interviews that this displacement of focus had consequences far beyond the specific domain of the history of sexuality. "Security, Territory, Population" (Foucault, 2007) contains a conceptual hinge, a key concept, that allows us to link together the political and ethical axes of Foucault's thought. Indeed, it is Foucault's analysis of the notions of conduct and counter-conduct in his lecture of 1 March 1978 that seems to me to constitute one of the richest and most brilliant moments in the entire course. Is is astonishing, and of profound significance, that the autonomous sphere of conduct has been more or less invisible in the history of modern (as opposed to ancient) moral and political philosophy. This article argues that a new attention should be given to this notion, both in Foucault's work and more generally. PMID- 22324075 TI - Foucault and the politics of our selves. AB - Exploring the apparent tension between Foucault's analyses of technologies of domination -- the ways in which the subject is constituted by power-knowledge relations -- and of technologies of the self -- the ways in which individuals constitute themselves through practices of freedom -- this article endeavors to make two points: first, the interpretive claim that Foucault's own attempts to analyse both aspects of the politics of our selves are neither contradictory nor incoherent; and second, the constructive claim that Foucault's analysis of the politics of our selves, though not entirely satisfactory as it stands, provides important resources for the project of critical social theory. PMID- 22324077 TI - [The proposed national licensure system for psychiatric professions and obstacles arising in interprofessional cooperation]. PMID- 22324076 TI - The survival of 19th-century scientific optimism: the public discourse on science in Belgium in the aftermath of the Great War (ca. 1919-1930). AB - In historiography there is a tendency to see the Great War as marking the end of scientific optimism and the period that followed the war as a time of discord. Connecting to current (inter)national historiographical debate on the question of whether the First World War meant a disruption from the pre-war period or not, this article strives to prove that faith in scientific progress still prevailed in the 1920s. This is shown through the use of Belgium as a case study, which suggests that the generally adopted cultural pessimism in the post-war years did not apply to the public rhetoric of science in this country. Diverse actors -- scientists, industrialists, politicians, the public opinion, and the military staff -- declared a confidence in science, enhanced by wartime results. Furthermore, belief in science in Belgium was not affected by public outcry over the use of mustard gas, unlike in the former belligerent countries where the gas became an unpleasant reminder of how science was used during the war. Even German science with its industrial applications remained the norm after 1918. In fact, the faith in science exhibited during the pre-war years continued to exist, at least until the 1920s, despite anti-German sentiments being voiced by many sections of Belgian society in the immediate aftermath of the war. PMID- 22324078 TI - [Cognition, behavior and emotion in psychotherapy]. PMID- 22324079 TI - [Cognition in relation to psychoanalysis]. PMID- 22324080 TI - [How to diagnose pervasive developmental disorders in adults]. PMID- 22324081 TI - We are united vision and resolve. PMID- 22324082 TI - The new world of health and safety. PMID- 22324083 TI - The dark side of the mining boom. PMID- 22324084 TI - Patient's page. Geriatric dental care. PMID- 22324085 TI - Tracking charitable care. PMID- 22324086 TI - Dental license renewal due dy January 1st or risk of license loss. PMID- 22324087 TI - Why do I volunteer on the Mobile Dental Unit? PMID- 22324088 TI - Unusual late occurrence of bowel obstruction following blunt abdominal trauma. AB - We report a case of late occurrence of small bowel obstruction due to stricture resulting from blunt abdominal trauma. On initial computed tomography (CT) scan, the patient had a mesenteric hematoma, which was managed conservatively. Approximately two weeks later, he complained of worsening abdominal pain and developed clinical signs of bowel obstruction. A repeat enhanced CT scan showed a stenotic loop of distal ileum adjacent to a large mesenteric mass. The loop was resected. We propose that post-traumatic intestinal stenosis be considered in the differential diagnosis in patients who have experienced blunt abdominal trauma and present later with clinical signs of bowel obstruction. PMID- 22324089 TI - Increase in primary and secondary syphilis cases in older adults in Louisiana. AB - Sexually active young adults and adolescents experience a majority of the burden of sexually transmitted diseases in the United States and public health resources are appropriately directed at these age groups. However, sexual health of older adults is often ignored. An analysis of sexually transmitted disease surveillance data from the Louisiana Office of Public Health show that both the numbers and rates of primary and secondary syphilis cases have increased in older age groups over the past 10 years. Clinicians must be aware of increased use of erectile dysfunction drugs in older persons as a possible risk factor for sexually transmitted diseases. Clinicians must also realize that a significant number of older persons display sexually risky behavior and safe sexual health counseling is often overlooked in this population. PMID- 22324090 TI - Benefits of newborn screening for cystic fibrosis in Shreveport, Louisiana, Cystic Fibrosis Center. AB - INTRODUCTION: Cystic Fibrosis (CF) is the second most common, life-shortening, inherited disorder occurring in childhood in the United States, after sickle cell anemia. More than 10 million Americans are unknowing, symptomless carriers of the defective cystic fibrosis gene. Cystic Fibrosis was included in the newborn heel stick screening in Louisiana, beginning July 2007. AIMS AND OBJECTIVES: 1) To assess and compare the nutritional status of Cystic Fibrosis patients in the newborn screened cohort (NBS) compared to the non-newborn screened cohort (non NBS) by measuring their weight for length/height percentile at 1, 2, and 3 years of age, 2) To compare the vitamin levels of CF patients in these two groups, 3) To compare the number of hospitalizations in the two groups, and 4) To compare the incidence of colonization of significant bacteria in the airways in these groups. METHODOLOGY: Out of 91 CF patients, 26 were excluded due to insufficient data. The sample was stratified into two groups; 1) Newborn screen (July 2007 to present) and 2) Non-Newborn screen (1971 to present). Recording and comparison of their weight for height or length; percent of patients showing decreased fat soluble vitamin A, D, and E levels; rate of hospitalization; and cultures at 1- 3 years of age were made. RESULTS: CF patients below 50th percentile of weight for height/length were 48.88% in Non-NBS and 33.33% in NBS at one year, 47.73% in Non NBS and 40% in NBS at two years, and 45.45% in Non-NBS and 25% in NBS at three years. CF patients below 10th percentile of weight for height/length were 13.33% in the Non-NBS and 5% in NBS at one year, 11.66% in Non-NBS and 0% in NBS at two years, and 6.81% in Non-NBS and 8.33% in NBS at three years of age. There was also reduction of vitamin A, D, and E deficiencies at one to three years in NBS compared to Non-NBS. However, these results were not statistically significant. The hospitalization rate of CF patients during the first three years of life was 86.66% in Non-NBS as compared to 68.42% in NBS. The colonization of (i) MRSA was 18.75% in Non-NBS and 36.84% in NBS, and (ii) Pseudomonas aeruginosa in Non-NBS was 59.37% and 36.84% in NBS at any point during the first three years. CONCLUSION: The study has shown that there has been an improvement in the nutritional status shown by a decrease in the percentage of patients below the 50th percentile and below 10th percentile of weight for height at one to three years of age after the implementation of NBS three years ago. There has also been a reduction in the vitamin deficiencies, hospitalizations, and colonization by Pseudomonas aeruginosa among the screened patients as compared to the CF patients diagnosed clinically. PMID- 22324091 TI - The distribution of physicians workforce in Louisiana: results from a cross sectional study. AB - For the past two decades, Louisiana's population health rankings as reported by the United Health Foundation have been among the lowest in the nation. In addition, the 2009 Commonwealth State Scorecards Report ranked the Louisiana health system performance, in terms of health outcomes, among the poorest in the nation. One reason for this disparity could be attributed to shortages of physicians and other healthcare resources in the state. These shortages were exacerbated by the damage from Hurricanes Katrina and Rita in 2005 to hospitals and physicians' practices in New Orleans and throughout the state. This descriptive cross-sectional study focused on the geographical dimension of access and on one of its critical determinants: the availability of physicians. The objective behind this study was to offer a better understanding of the determinants of geographical imbalances in the distribution of physicians in the state of Louisiana. This study is part one of a three-part series that examines the association between total physician supply, primary care, and specialty care supply on mortality amenable to healthcare (MAHC). PMID- 22324092 TI - A novel hemodynamic observation: worsening of tricuspid regurgitation with dobutamine infusion during a hemodynamic study. AB - Dobutamine has been shown to improve right ventricular contractility and cardiac output in right ventricular failure. However, the effect of dobutamine in the select group of patients with severe tricuspid regurgitation (TR) has not been described previously. We report the case of a patient with severe TR and right heart failure who developed ventricularization of right atrial pressure after dobutamine infusion. This highlights the potential worsening of TR and right heart failure in patients with TR receiving dobutamine. PMID- 22324093 TI - Recognizing reemerging and recently described rickettsial infections in the United States. PMID- 22324094 TI - A tribute to Charles V. Sanders, MD, on the occasion of his receiving the 2011 Spirit of Charity Award. AB - Dr. D. Luke Glancy, MD, presented the following speech at the Spirit of Charity Gala, October 14, 2011, at the Sheraton Hotel, New Orleans. The speech, which is reprinted here in its entirety, was for Dr. Charles V. Sanders, MD, on the occasion of his receiving the 2011 Spirit of Charity Award. PMID- 22324095 TI - Asbestosis in Louisiana: a descriptive review and demographic analysis of hospitalizations for abestosis, 1999-2009. AB - Asbestosis is a debilitating, chronic, lung disease with no known treatment and most commonly occurs among workers in certain occupational settings. As a condition highly associated with occupational exposure, its incidence has been affected by changes in industry standards. In particular, the bans on both production and new uses of asbestos fibers put in place during the past 20 to 30 years have significantly reduced occupational exposures. Despite these restrictions, asbestos can still be found in many products. Louisiana has more facilities that produce, process, or use asbestos than any other state in the US. Health outcomes associated with asbestos exposure include asbestosis, mesothelioma, and lung cancer. To evaluate the impact of asbestos exposure on Louisiana residents, Louisiana Hospital Inpatient Discharge Data (LAHIDD) from 1999-2009 was analyzed. Results indicate that asbestosis hospitalizations have remained steady over the 11-year period with approximately 295 cases per year. White males have the highest rates, and cases are clustered geographically. Overall, Louisiana's rate is significantly greater than the US rate (p < 0.0001). PMID- 22324096 TI - ECG of the month: ECG in a man with a diagnosis of asthma. Normal sinus rhythm, left atrial enlargement, right axis deviation of the QRS complex, right ventricular hypertrophy and nonspecific T-wave change including a slightly long QT interval. PMID- 22324097 TI - An asymptomatic male with an elevated alkaline phosphatase. PMID- 22324098 TI - Christmas treat to chronic cough. PMID- 22324099 TI - Dentistry is challenging: cosmetic dentistry even more. PMID- 22324100 TI - Dentistry is challenging: cosmetic dentistry even more. PMID- 22324101 TI - Dentistry is challenging: cosmetic dentistry even more. PMID- 22324102 TI - Guidelines and specialty bias. PMID- 22324103 TI - Diabetes mellitus: update and relevance for dentistry. AB - In light of growing evidence of the association between oral and nonoral diseases, some investigators believe that oral disease is a clinically useful predictor of nonoral conditions in certain individuals. As the dental profession has become more involved in treating medically compromised patients, dentistry has gone from being an "oral health profession" to being part of the general health team. As a result, a partnership between dentists and physicians that involves an expanded notion of oral-medical communication during the course of treating such patients should be embraced in order to better serve these patients. Michael Glick, senior editor of the Journal of the American Dental Association, believes that oral health providers should take an active role in screening certain groups for common medical conditions, ie, to check the patient's blood pressure, plasma glucose, and cholesterol for indications of heart disease and DM. Furthermore, dentists can be part of the diabetic patient's support network by becoming actively involved in monitoring blood glucose levels and blood pressure, as well as reminding patients of the importance of having their regular medical exams. Dentists are not going to diagnose or treat a systemic disease, but early detection will certainly result in better medical and dental outcomes. It is the dentist's role to be a part of the healthcare team in order to help reduce the incidence and adverse impact of diabetes. PMID- 22324104 TI - Revolutionary advances, Part 3: Pursuit of the 3-D cork. PMID- 22324105 TI - Efficient placement of implant overdenture attachments. PMID- 22324106 TI - The "first implant": protocol for the GP, Part 3. PMID- 22324107 TI - Combining orthodontics with conservative restorative care. PMID- 22324108 TI - Prerestorative ortho to maximize aesthetics and function. PMID- 22324109 TI - Bioesthetic dentistry, Part I. PMID- 22324110 TI - Digital radiography for tots and teens. PMID- 22324111 TI - Showing respect for the "neighbors'! PMID- 22324113 TI - Downgrading or de-banding. PMID- 22324112 TI - The diode laser in treating ulcerative oral lesions. PMID- 22324114 TI - Advancement in our careers. PMID- 22324115 TI - Perioperative death: a critical reflection-on-action. AB - Perioperative death is thankfully not a regular occurrence in UK operating theatres. However, when it does occur the perioperative practitioner is often denied the opportunity to grieve. The use of a clinical supervision session enabled a critical reflective approach to be followed after the death of a patient in the operating theatre. PMID- 22324116 TI - Evaluating the effect of music on patient anxiety during minor plastic surgery. AB - AIM: The study sought to assess the effectiveness of music on patient anxiety levels during minor surgery. METHODS: Eighty patients attending a minor plastic surgery out-patient department were assessed using the Spielberger State-Trait Anxiety Inventory Questionnaire. Forty participants in the experimental group listened to music which was self selected and played during their operation. Forty participants in the control group received the standard care during their operation but with no music. The questionnaire was used to collect data pre and postoperatively. During the recovery period all participants were asked to reflect on their level of anxiety during surgery while completing the questionnaire. Analysis was carried out using Statistical Package for Social Sciences (SPSS) version 12. RESULTS: The postoperative mean anxiety score of the control group was 33.5 (SD 10.6). The mean anxiety score for the experimental group was 30.52 (SD 9.82). Statistical analysis revealed that there was no significant difference among those who did and did not listen to music during their procedure. CONCLUSION: Although the researcher did not find statistically significant differences in the selected outcome measures, the intervention seemed to be enjoyed by the patients in the experimental group. Minimising anxiety prior to and during a minor operation may help promote relaxation and enhance patient comfort. PMID- 22324117 TI - Surgical care practitioner practice: one team's journey explored. AB - Surgical practice in the UK changed in 1993, when Suzanne Holmes and her cardiac surgical colleagues introduced the surgical care practitioner role (SCP). Within a consultant led extended surgical team, SCPs work alongside a variety of healthcare practitioners to provide safe patient care, meet service demands and educate the future surgical workforce. This article reviews the history of this development over the last fifteen years in the context of a busy orthopaedic department and discusses some unforeseen consequences. PMID- 22324118 TI - The perioperative management of skeletal metastases. AB - Bone metastasis is a common problem affecting a significant proportion of patients with metastatic cancer. Bone metastasis can present in a number of ways and the patients may need surgical stabilisation of their lesions. There are many important considerations in the care of these patients that need to be borne in mind including their increased anesthetic risks and potential risk of complications. There are continuous developments in the prevention, diagnosis and treatment with advances in imaging, orthopaedic technique and medication, particularly radiopharmaceuticals and cytotoxic, endocrine treatments with newer treatments based around the tumour cell-osteoclast interaction. Having a better understanding of these considerations and developments is important in allowing the optimisation of the care of the patient with bone metastasis. PMID- 22324119 TI - The management of rotator cuff tears in the elderly. AB - Rotator cuff tears occur commonly in the elderly causing significant pain and disability. In light of new treatment options developed over recent years, this article reviews the diagnosis and operative options available for this condition. PMID- 22324120 TI - The early days of diverticula of the colon. AB - As a 17 year old first-year medical student at Oxford University in 1943, busily dissecting a cadaver in the Anatomy Department, I could not help noticing a series of peculiar pea-sized swellings along the course of the sigmoid colon. I showed these to our Professor of Anatomy, the much respected Sir Wilfred Le Gros Clarke FRS, who said 'Those are diverticula, my boy. As an Oxford student you should know, (which, in fact, I did not!), that the word 'diverticulum' is Latin for a 'wayside house of ill fame or ill repute', and well do they deserve that descriptive term'. I carefully excised the affected piece of colon, put it in a bottle of formalin and, at the end of term, put it onto the mantelpiece of my bedroom at home. A few years later, my mother, in a clearing-up mode, threw the dusty bottle away. What a pity that I am unable to produce a photograph of my specimen to illustrate this article! PMID- 22324121 TI - Perspectives on organ and tissue donation among Chinese Canadians. AB - Organ and tissue transplantation offers great potential for improving quality of life and reducing health care costs associated with end-stage organ failure. However, substantial and persistent shortages of organs and tissues for transplantation exist in Canada and there is a growing gap between those on transplant waiting lists and the organs available for transplantation. Every Canadian should have the opportunity to consider organ and tissue donation and transplantation in a culturally sensitive and respectful manner. During consultation with the Chinese Canadian community in Toronto, it was found that a clear understanding of the attitudes and values of Chinese Canadians regarding organ and tissue donation could assist health professionals in making ethnoculturally sensitive requests for donation to members of this community. PMID- 22324122 TI - Iron replacement and supplementation in patients with chronic kidney disease. AB - Interest in optimizing iron management in the treatment of anemia of CKD is growing due to concerns that high doses of ESAs may have deleterious effects and the high cost of ESAs in comparison to iron therapy. International guidelines have defined iron targets for this patient population, but there are some unanswered questions with respect to long-term use of iron, such as the maximum TSAT or ferritin concentration and concerns with oxidative stress. Large head-to head safety studies of the different i.v. iron preparations have not been performed to date and current safety data rely on small studies and spontaneous adverse event reporting. Interprofessional management of anemia, including iron therapy, has shown beneficial effects and should be encouraged. PMID- 22324123 TI - The miracle of midwifery. PMID- 22324124 TI - Landmark study endorses safety of homebirth and midwife led care. PMID- 22324125 TI - Those who can, teach. AB - Teachers can have a profound effect on us all, both good and bad. In this paper the effect two individual midwives had on Margaret Murphy's evolution as a midwife will be examined. They were very different: one was formal and the other informal; the classroom was the setting for one, the clinical area for the other; each had her own unique style and way of looking at the world; they were very different in manner and in approach. However they shared a philosophy of women centred, normal birth which they espoused in all aspects of their working lives. PMID- 22324126 TI - Language matters! AB - Medical terminology and the language which we use, as healthcare professionals, can be deemed as disempowering towards women and their pregnancy/birthing experience. This article aims to highlight the need for a change in practice through 'thinking before we speak' and realising the importance of language choices and informal discussions in building successful relationships with the women we care for. Rebecca Allison discusses various phrases and forms of communication which need addressing. PMID- 22324127 TI - To push ... or not to push? AB - I was formally asked by my supervisor of midwives to reflect upon two episodes of care. Both of these involved women who would be termed as 'low risk' primigravida and in both instances the women had considered whether, had they been advised against pushing when it was 'too soon', they might have avoided caesarean sections. To help this process I used my own reflection triangle: 'What happened ... Was it OK ... What about next time?' informed by the Gibbs model (1998). In this paper I present my reflections alongside my reflection triangle. PMID- 22324128 TI - Migration and maternity in the age of superdiversity. AB - The UK has entered an era of superdiversity with our communities being more diverse than ever before. Migration has contributed to rising birth rates, and poor birth outcomes have been increasingly associated with ethnicity, often in areas with high concentrations of migrants. This article sets out the findings of a study looking at the maternity needs and experiences of migrant women and professionals living in the West Midlands. The study found that migrant women tended to book late or drop out of the maternity system due to a range of barriers including lack of understanding of the system, lack of information, poor language skills and poverty. Migrant women often had negative birth experiences and did not receive the follow on care they needed. Professionals recognised many of the problems migrant women experienced but lacked the time and resources to meet needs. The article concludes by recognising that additional training and time are needed to help professionals to address those needs and signposts the reader to good practice. PMID- 22324129 TI - Supervision: a 'fresh eyes' approach. AB - As recent reports question the safety of some maternity services and of the accuracy of identifying risk factors in midwifery practice, this article advocates the use of 'fresh eyes' reviews of our own practice, that of our peers and the practice within our organisations. If, as the literature indicates, there is no evidence of sustained transformational change through compliance as opposed to commitment, then our engagement and motivation to adopt 'fresh eyes' approaches to our practice, may lead to improved patient outcomes, including rates of mortality. PMID- 22324130 TI - LSAMO forum UK strategic plan. AB - Over the years, the LSA role and function have developed and strengthened significantly and it is crucial that this development continues in the new NHS. The biennial LSAMO UK conference which is entitled Future proofing supervision will launch the strategic plan for 2012-2015. It is essential that LSAMOs and supervisors of midwives (SoMs) look to the future to continue to maintain safety and protect the public, but within a modernised forward thinking framework. The forum will work collaboratively to encourage a greater consistency in the provision of supervision to ensure the standards set by the NMC for the LSAs and the supervision of midwives are met. Protecting the public and supporting safe midwifery practice will continue to be the driving principles behind the LSAMO UK forum's work plan. The specific challenges to LSAMOs will be to continue providing leadership and support and be pivotal in addressing the future significant challenges faced by the NHS throughout the UK. PMID- 22324131 TI - Changing practice: physiological cord clamping. AB - Every baby deserves the best start to life. Receiving the full quota of blood from the placenta directly after birth has profound short and long-term benefits for the baby; these have been extensively researched and documented. This article discusses a student midwife's experience of participating in reviewing third stage guidelines to incorporate this growing evidence base into clinical practice within a large London NHS Trust. A new local guideline (unpublished) recommends every baby (where clinically possible) has the opportunity to benefit from 'physiological cord clamping'. The aim of the article is to inspire midwives and student midwives to become involved with similar activities within their own trusts. PMID- 22324132 TI - A new beginning in India. PMID- 22324133 TI - Changing childbirth in India. PMID- 22324134 TI - Use of technology in childbirth. 4. Electronic fetal monitoring. PMID- 22324135 TI - Motivational messages: lead a Baby Friendly Initiative community project. AB - 2011 saw Baby Friendly Initiative (BFI) success in the towns of Blackburn with Darwen. The towns serve around 2,500 new babies a year, have significant social deprivation and mixed ethnicity. Commitment was made by the Trust and Local Authority, to progress to meeting full BFI standards by commissioning the Acute Trusts Infant Feeding Coordinator (midwife) to lead on the project and the change needed. Numerous challenges were met along the way, such as capacity to lead and deliver (leading to the recruitment of Donna), swine flu, GP training, organisational changes and loss of ante- and postnatal interventions. This was the first Community Trust in England to achieve full accreditation without follow up visits. This article hopes to inspire other Trusts to get started, keep going and don't let go until you get there--because it's worth it. PMID- 22324136 TI - Jenny Fraser reports from the Royal College of Midwives Legal Birth Conference. Thursday 7 July 2011. Cavendish Conference Centre London. PMID- 22324137 TI - For the love of the job. PMID- 22324138 TI - Characterizing thermoluminescence properties of calcium halophosphate fluorescent coating powder for radiation dosimetry. AB - The thermoluminescence (TL) and other properties of calcium halophosphate fluorescent coating powder were studied in detail with the sole aim of ascertaining its suitability for use as a dosimetric material. The shape of the glow curve (peaks at about 125 degrees C and 350 degrees C) as well as its fairly linear dose response even at very high doses are indicative of its suitability. Optical properties of the material were studied using Infrared spectroscopy (IR) and UV-Visible spectrophotometry. The IR spectrum shows a prominent peak at 3425.9 cm(-1) indicating the presence of OH and N-H bonds. The material absorbs sharply at wavelength between 196 nm and 220 nm. The material exhibits high transmittance at various peaks with corresponding wavelengths from 300 to 831 nm. This material can also find application in radiation therapy associated with very high accident dosimetry as well as in material testing. PMID- 22324139 TI - Removal of Ni (II) from aqueous solutions by adsorption onto Ricinus communis seed shell activated carbons. AB - The adsorption studies on the removal of Ni(II) from aqueous solution using Ricinus communis seed shells activated carbon and polypyrrole coated Ricinus communis seed shells activated carbon were carried out under various experimental conditions. The effects of various process parameters have been investigated by following the batch adsorption technique. Adsorption data was modeled with Freundlich, Langmuir and tempkin adsorption isotherms. Thermodynamics parameters such as DeltaH0, DeltaS0, and DeltaG0 were calculated indicating that the adsorption was spontaneous and endothermic nature. A mechanism, involving intra particle diffusion and surface adsorption, has been proposed for the adsorption of Ni(II) onto the adsorbent. Adsorbent used in this study is characterized by FTIR and SEM before and after the adsorption of metal ions. PMID- 22324140 TI - Assessment of sediment accumulation and capacity of reservoir by analytical approach--a case study. AB - Sedimentation in reservoirs is a major problem in all countries. A study on sediment accumulation in a reservoir is necessary for effective reservoir planning and watershed management systems. In this study, the volume of sediment deposition in the Vaigai reservoir is calculated based on the analytical approach. The historical water inflow for the years 1959 to 1999 (41 years) are used to calculate the water inflow for future years. The volume of sediment accumulation in the reservoir is predicted using the calculated water inflows. Based on the volume of sediment accumulation, the capacity of reservoir and the percentage of loss in capacity were also calculated. The result obtained from the analytical method is compared with the actual capacity of reservoir and found that the calculated values match well with the actual results. PMID- 22324141 TI - Parameter optimization of unbaffled circular surface aeration tank. AB - The efficiency of the surface aeration systems is generally governed by the geometric and dynamic parameters. The geometry is important because successful translation of the laboratory finding can be scaled up to field installations. Experimental optimization of the geometrical parameters (classical approach of one parameter variations at a time) has certain limitations, because it assumes a linear relationship among the various geometric parameters. In the real experimental process, it is not possible to vary all the parameters simultaneously. In such a case, the model of the system is built through computer simulation, assuming that the model will result in adequate determination of the optimum conditions for the real system. In this paper, two approaches have been used to model the phenomena in unbaffled circular surface aerators: i) Multiple regression and ii) Neural network. It has been found that neural network approach is showing better predictability compared to the multiple regression approach. In process of optimization, the pertinent dynamic parameter is divided into a finite number of segments over the entire range of observations. For each segment of the dynamic parameter, the neural network model is optimized for the geometrical parameters spanning over the entire range of observations. Thus each segment of the dynamic parameter has its set of optimal geometrical conditions. Results obtained are having less variation among them and they are very nearer to the experimental optimal conditions. Input parameter significance test of neural network model reveals that blade width of the rotor is the most significant geometric parameter for the aeration process. PMID- 22324142 TI - Performance of upflow anaerobic filter in the treatment of distillery spentwash. AB - Distillery spentwash, owing to its high COD, BOD along with obnoxious odour and dark colour presents several operational challenges when applying biological treatment technologies. Conventional treatment techniques achieve only about 70% COD removal, with the treated effluent still exceeding the limits prescribed by the Pollution Control Board. Hence, the need of the hour is an efficient technology to reduce the polluting capacity of the distillery wastes. Keeping this in mind, an investigation using a laboratory-scale upflow anaerobic filter (UAF) to study carbonaceous removal of distillery spentwash under mesophilic conditions has been attempted. The effect of hydraulic loadings on COD removal has been evaluated at different COD concentrations ranging from 2000 to 13000 mg/L. The COD removal percentage during the period of investigation was found to be in the range of 54.8% to 88.7%. The biogas yield was observed to be in the range of 0.33-0.45 m3/kg of COD destroyed. PMID- 22324143 TI - A case study for removal of sulphur-di-oxide from exhaust flue gases at thermal power plant, Rajasthan (India). AB - The aim of this study is to reduce the percent SO2 in environment and to produce a byproduct with SO2, to control air pollution. The present work envisages a situation that compares the efficiency of three different reagents, viz. sodium hydroxide, calcium hydroxide and waste product of water treatment plant containing CaO in removal of SO2 that would be generated in this situation. Various parameters were also observed with variation involving percent concentration of reactants, pH of the solution, time for reaction , temperature of solution and flow of flue gas in impingers. Pet coke with lime stone is being used for power generation in power plant during the experiment, the pet coke having 6% sulphur resulting in emission of SO2. Hence experiments have been conducted to trap these gases to produce sulphates. Waste product of water treatment plant, calcium hydroxide, and sodium hydroxide in various permutation and combination have been used with control flow by SO2 monitoring kit for preparation of calcium sulphate and sodium sulphate. Thus sodium hydroxide turned out to be better as compared to calcium hydroxide and sludge. It is also concluded that pH of the solution should be alkaline for good absorption of SO2 and maximum absorption of SO2 found in direct passing of SO2 in impinger as compared to indirect passing of SO2 in impingers. Good absorption of SO2 found at temperature range between 20-25 degrees C and it seems to be optimum. Maximum recovery of SO2 was obtained when the reaction took place for long time period. PMID- 22324144 TI - Enhanced coagulation for turbidity and Total Organic Carbon (TOC) removal from river Kansawati water. AB - The objective of this study was to determine optimum coagulant doses for turbidity and Total Organic Carbon (TOC) removal and evaluate the extent to which TOC can be removed by enhanced coagulation. Jar tests were conducted in the laboratory to determine optimum doses of alum for the removal of turbidity and Natural Organic Matter (NOM) from river water. Various other water quality parameters were measured before and after thejar tests and included: UV Absorbance (UVA) at 254 nm, microbial concentrations, TDS, conductivity, hardness, alkalinity, and pH. The optimum alum dose for removal of turbidity and TOC was 20 mg/L for the sample collected in November 2009 and 100 mg/L for the sample collected in March 2010. In both cases, the dose for enhanced coagulation was significantly higher than that for conventional coagulation. The gain in TOC removal was insignificant compared to the increase in coagulant dose required. This is usual for low TOC (< 2 mg/L)--high alkalinity water. Other water samples with higher TOC need to be tested to demonstrate the effectiveness of enhanced coagulation. PMID- 22324145 TI - Improved design of a tangential entry cyclone separator for separation of particles from exhaust gas of diesel engine. AB - An effective design of cyclone separator with tangential inlet is developed applying an equation derived from the correlation of collection efficiency with maximum pressure drop components of the cyclone, which can efficiently remove the particles around 1microm of the exhaust gas of diesel engine. PMID- 22324146 TI - Measurement of alpha radioactivity and dose assessment in common food crops with SSNTD. AB - Radioactivity is present everywhere in the environment including soil, from where it transfers to vegetation and plants. These vegetations when taken as food result in transfer of the radioactivity to human beings which may cause health hazards. Thus information about the presence of radioactivity in vegetation, plants and soil is highly desirable. In this context, measurements of alpha radioactivity present in soil as well as in some of the staple food crops which form the main components of the composite Indian diet are presented in this study. Assessment of effective dose rate has also been done. The total alpha activity in soil has been found within 100-700 Bq kg(-1) and in food within 10 200 Bq kg(-1). The annual effective dose rate in food crops has been estimated in the range of 0.8-300 i S v. PMID- 22324147 TI - Assessment of air pollution stress on some commonly grown tree species in industrial zone of Durgapur, West Bengal, India. AB - The present study deals with the biochemical responses of some selected tree species with respect to increased air pollution in Durgapur industrial city in India. Areas in vicinity to industries possess very high concentrations of suspended particulate matter (571 microg/m3), SOx (132 microg/m3) and NOx (97 microg/m3) which shows significant correlations (p < 0.05) with the biochemical constituents of stressed plants. Plants growing in industrial zone exhibit a considerable decline in total chlorophyll (34.97-59.81%), soluble sugars (23.85 33.16%) and protein content (21.59-47.13%) and increase in ascorbic acid (81.87 238.53%) and proline content (123.47-284.91%). Of the studied tree species, Shorea robusta (9.78 +/- 0.095), Alstonia scholaris (8.76 +/- 0.084), Peltophorum pterocarpum (8.99 +/- 0.13) and Albizia lebbeck (7.71 +/- 0.012) were found to be more tolerant with higher Air Pollution Toblerance Index (APTI) and Tectona grandis (6.13 +/- 0.276), Lagerstroemia speciosa (7.075 +/- 0.18) and Delonix regia (6.87 +/- 0.079) were sensitive with lower APTI values. Therefore, plant species with higher APTI value, being more resistant, can be used as pollutant absorbent to reduce the pollution level and are suitable for plantations in industrial areas. PMID- 22324148 TI - Mitigation of air pollution and carbon footprint by energy conservation through CFLs: a case study. AB - Electricity consumption of compact fluorescent lamps (CFLs) is low, making them a useful tool for minimizing the rapidly increasing demand of electrical energy in India. The present study aims to project the likely electricity conservation in a scenario of complete replacement of existing Fluorescent Tubes (FTs) by CFLs at CSIR-NEERI (National Environmental Engineering Research Institute) visa vis the financial repercussions and indirect reduction in emissions of greenhouse gases, e.g. CO2, N2O, CH4 and other air pollutants, e.g. SO2, NO, suspended particulate matter (SPM), black carbon (BC) and mercury (Hg) from coal fired thermal power plants. The calculations show that the Institute could save around 122850 kWh of electricity per annum, thereby saving approximately INR 859950/(USD 18453.86) towards electricity cost per annum and would be able to minimize 44579.08 kg of CO2-C equivalent (over 100 year time horizon), 909 kg SO2, 982.8 kg NO, 9.8 kg of BC, 368.5 kg SPM, 18.4 kg PM10 and 0.0024 kg Hg emissions per annum from a coal fired thermal power plant by conserving electricity at the institute level. PMID- 22324149 TI - Arsenic level in ground and surface water in predominantly rural areas of Golaghat sub-division in Golaghat district, Assam, India. AB - This paper reports the quality of ground and surface water with respect to Arsenic from 33 different sources in predominantly rural area of Golaghat sub division in Golaghat district of Assam (India). Water samples were collected during the pre-monsoon (Feb) and post-monsoon (Oct) seasons of 2008. The results are analyzed in the light of possible health hazards from Arsenic in relation to their maximum contaminant level (MCL) 10 ppb recommended by USEPA (2001) guideline value as well as WHO (1993,2004) instead of previous WHO (1984) guideline value 50 ppb. The quality of drinking water in the district is not satisfactory with respect to presence of Arsenic .The As concentrations varied from 0 to 220 ppb during pre-monsoon and 1 ppb to 187 ppb during post-monsoon. The high values of As were observed in Forkating, Fatual (220 ppb) and Bahbari (187ppb) in pre-monsoon and post-monsoon seasons respectively. It was observed that about 30.3% of samples have As concentration 0-10 ppb, 27.27% of samples have 11-50 ppb and remaining samples, i.e. 46.46% have greater than 50 ppb in pre monsoon (Feb. 2008) and 27.27% of samples have As concentration 0-10 ppb, 39.39% of samples have 11-50 ppb and remaining samples, i.e. 33.33% have greater than 50 ppb in post-monsoon (Oct. 2008). PMID- 22324150 TI - Statistical assessment of groundwater resources in Washim district (India). AB - Groundwater quality of Washim district of Maharashtra (India) was assessed using quality parameters and water quality index (WQI). In this study, the WQI was analyzed by using pH, turbidity, temperature, nitrates, total phosphates, dissolved oxygen, biochemical oxygen demand, total solids, total coliforms and faecal coliforms, respectively for residential and commercial uses. All the parameters were analyzed both in pre-monsoon and post-monsoon seasons to assess the groundwater quality and seasonal variations. The parameters like turbidity, solids and coliforms showed the seasonal variations. The WQI varied from 72 to 88 in pre-monsoon season and 64 to 88 in post-monsoon season. The results indicate that all groundwater samples in the study area have good water quality in pre monsoon season but in post-monsoon season 9 percent samples indicated the change in water quality from good to medium, which reveals seasonal variation and groundwater quality deterioration. PMID- 22324151 TI - Fluoride concentration in ground waters at Raebareli district (India). AB - Extensive monitoring and assessment related studies of groundwaters in three blocks, viz. Deeh, Dalmau and Unchahar of the Raebareli district were carried out. Fluoride concentrations in water samples were measured by SPANDS methods. The results showed that the fluoride level in the water samples was 0.80 +/- 4.20 mg/L. PMID- 22324152 TI - Physico-chemical characteristics of ground and surface water in Gohpur sub division of Sonitpur district, Assam (India). AB - According to WHO, about 80% of all the diseases of human beings are caused by water. Since these diseases are directly related with human health, it is necessary to bring awareness among the present and future generation about the consequences of water pollution. Therefore, in this study 34 samples from different sources such as dug wells, bore wells, hand pumps and ponds, where no information is available, were collected during 2008.The samples were analyzed for different physico-chemical parameters like chloride, sulphate, nitrate, sodium, potassium, calcium, magnesium, iron, copper, cadmium, chromium, lead and zinc using standard methods. The result indicated that chloride and nitrate concentrations in all the sources were within the permissible limit, but ponds contained high amount. The concentrations of sulphate, sodium and zinc in dug wells and bore wells were very high and the concentrations of calcium and chromium were within the permissible limit. In case of lead and calcium their concentrations in ponds were higher than the other sources but chromium was not detected in ponds and hand pumps. The iron and copper concentrations in all the sources exceeded the WHO value, particularly dug wells and bore wells contained high concentrations. Magnesium content was greater than potassium and less than sodium in dug wells and bore wells, but in ponds its concentration was greater than the other sources. In our investigation the results indicate that TDS, EC, pH, BOD, DO, COD, TSS were found very high. In 76% samples turbidity exceeded WHO guideline value 5NTU. It was found that 97% and 76% of the sources were positive for TC and FC. Overall analysis revealed that 11 samples were fit for drinking purpose with respect to the parameters studied. PMID- 22324153 TI - Noise monitoring during festive period at Nagpur (India). AB - The unwanted sound is referred to as noise. Prolonged exposure to such noise has ill effects on humans as well as on animals. Also, it is one of the environmental pollutants. The sources of noise pollution are present well within our houses. External factors add to additional noise pollution. It has direct impact on the hearing capacity. Apart from this, it also has adverse effects on the mental state of a human being. Noise pollution is a major problem during various festivals. The present study deals with the monitoring of noise levels at different locations during Ganesh festival. The monitoring was done at commercial, residential and silence zones. The study revealed that the noise level exceeded the prescribed limits at all the locations. Also, the restriction of 10 p.m. for noise was not followed by the general public. PMID- 22324154 TI - Ecological and socio-economic assessment of Varthur wetland, Bengaluru (India). AB - Wetlands are the most productive ecosystems, recognized globally for their vital role in sustaining a wide array of biodiversity and provide goods and services. But presently increased anthropogenic activities such as intense agriculture practices, indiscriminate disposal of industrial effluents and sewage wastes have altered the physical, chemical as well as biological processes of wetlands, which is evident from the present study carried out to assessVarthur wetland in India. Coastal wetland ecosystem in the world has 14,785/ha US$ annual economic value. An earlier study of relatively pristine wetland in Bengaluru revealed the value of ? 10,435/ha/day while the polluted wetland showed the value of ? 20/ha/day. On the contrary Varthur, a sewage fed wetland has a value of ? 118.9/ha/day. The pollutants and subsequent contamination of the wetland-Varthur has telling effects such as disappearance of native species, dominance of invasive exotic species (such as African catfish), in addition to profuse breeding of disease vectors and pathogens. Water quality analysis revealed high phosphate (4.22-5.76 ppm) level in addition to the enhanced BOD (119-140 ppm) and decreased DO (0-1.06 ppm). The amplified decline of ecosystem goods and services with degradation of water quality necessitates the implementation of sustainable management strategies to recover the lost wetland benefits of Varthur. PMID- 22324155 TI - Geochemical studies of granitic rocks of Kallur area, Manvi Taluk, Raichur district, Karnataka (India). AB - The geochemical data is much widely used in establishing the overall chemical relation existing between the different rock types with their parentage. A major impetus for this shift comes not only from the need to understand and quantify better the spatial and temporal evolution, with emphasis on the younger greenstone belts (Kallur copper formations), but also from the recognition that such knowledge could form the basis for the sustainable development of our natural resources. In addition, the recurrence of natural hazards has reinforced the need to learn more about the mechanics and to develop predictive modeling with advanced technical tools. This paper is emphasizing on Granodiorites of Kallur area of Manvi Taluk, Raichur District to substantiate the classical approaches of exploration and data gathering through quantitative methods of data processing and interpretation. The trilinear diagram indicates that the granites are rich in Potash and Soda. This clearly indicates that Granites are fairly rich in K2O than Na2O. PMID- 22324156 TI - Biodegradation of methyl parathion and endosulfan using Pseudomonas aeruginosa and Trichoderma viridae. AB - Microorganisms play an important role in the bioconversion and total breakdown of pesticides in the environment. This study was conducted to assess the pesticide degradation (endosulfan and methyl parathion) ability of the bacteria and fungi (Pseudomonas aeruginosa and Trichoderma viridae). The screening test conducted to reveal the ability to degrade endosulfan and methyl parathion shows that Trichoderma viridae was effective compared to Pseudomonas aeruginosa. The pesticide degradation was estimated by optical density method. Methyl parathion was highly degraded compared to endosulfan. This study clearly proves that pesticides and their residue degradation can be accelerated by employing microbes which can be effectively utilized both as biocontrol agent and soil cleanser. PMID- 22324157 TI - Bioremediation of distillery effluent by a consortium of microbial isolates. AB - Microbial consortium was made for the bioremediation of distillery effluent. Consortium was made with a combination of three isolates of white rot fungus (WRF) and Pseudomonas sp and Aspergillus sp., which locally isolated from distillery effluent. Among WRF, Isolate--WR 3 produced maximum ligninolytic enzymes along with a combination of other fungal isolates. WR-3 produced maximum decolourization zone (32.0 mm) inoculated with Brillant blue dye plates within 15 days of incubation as compared with other WRF Isolates. It showed a highest lignolytic enzyme activity on 14th day in still flasks studies as compared to other WRF Isolates. The consortium of all the isolates including WRF 3 showed significantly better variations in reducing colour (85.4.%), dissolved sulphites (98.8%), sulphates (54.5%), COD (57.5%) and BOD (55.2%) respectively on 15 days of incubation compared to other isolates when used alone. PMID- 22324158 TI - Municipal solid waste management through vermicomposting employing exotic species of earthworm Eudrilus eugeniae. AB - Majority of municipal (urban) solid waste (MSW) is disposed of in landfills (anaerobic composting). However, this disposal system is reported to produce hazardous environmental impacts and new policies are initiated to protect the environment from such impacts by discouraging the practice of disposal of solid waste in landfills. Eco-friendly disposal alternatives to landfills need to be explored. One of the technological options for treatment and disposal of organic solid wastes is vermicomposting. Commercial vermicomposting is reported to be practicable for treatment and disposal of many organic solids and byproducts in agricultural production and processing industries. However, this alternative has not been tried for MSW on large scale. This paper highlights the application of vermicomposting for treatment of organic solid waste, generated at urban residential area at Pune [organic component of this urban solid waste (MSW)]. Vermicomposting was tried on this segregated solid waste using exotic species of earthworm--Eudrilus eugeniae--commonly called 'African Night Crawler'. Bench scale reactor studies were carried out on organic solid waste under controlled optimum environmental conditions (moisture content: 48-52 percent, pH: 7.0-7.2, temperature: ambient), with variable vermi-loading [40-80 g of worms/kg of urban solid waste (MSW)]. Characteristics of solid waste were monitored through conventional parameters and additional environmental parameters like BOD5 and COD. The results of investigative studies are encouraging and indicate that organic solid waste can be treated in a reasonable period of 32-34 days through vermicomposting with around 60 percent reduction in the volume. PMID- 22324159 TI - Aquaculture in artificially developed wetlands in urban areas: an application of the bivariate relationship between soil and surface water in landscape ecology. AB - Wetlands show a strong bivariate relationship between soil and surface water. Artificially developed wetlands help to build landscape ecology and make built environments sustainable. The bheries, wetlands of eastern Calcutta (India), utilize the city sewage to develop urban aquaculture that supports the local fish industries and opens a new frontier in sustainable environmental planning research. PMID- 22324160 TI - A key message of the American College of Surgeons inspiring quality: highest standards, better outcomes. PMID- 22324161 TI - Billing Medicare for orders and referrals. PMID- 22324162 TI - When does EMTALA's stabilization requirement end? PMID- 22324163 TI - CoC Chair reflects on evolution of cancer care: new patient-centered standards represent another milestone. PMID- 22324164 TI - Palliative intervention in Ethiopia: the challenges and rewards of medical missionary work. PMID- 22324165 TI - Governors' Committee on Physician Competency and Health: an update. PMID- 22324167 TI - Working to evaluate and inspire through accreditation. PMID- 22324166 TI - States use Web-based strategies to promote grassroots advocacy. PMID- 22324168 TI - Modesty and the skin: why they shouldn't mix. PMID- 22324169 TI - Historical diagnosis & treatment: sycosis. PMID- 22324170 TI - Origin and evolution of syphilis: drifting myth. AB - The venereal form of treponematosis, caused by the spirochete Treponema pallidum, plagued every major city in the preantibiotic era. "Civilization means syphilization," was an idea touted by Richard von Krafft-Ebing in the late 19th, and early 20th centuries that the effects of modern life make men more susceptible to syphilis and other diseases. Christopher Columbus was thought of as an importer of syphilis to Europe. Because his serendipitous voyages to the New World initiated the process of Spanish colonization, which foreshadowed general European colonization of the New World, it is difficult to rule out the cultural and political animosity created by Columbus and his men. These recent revelations are intriguing and may create dialogue that may subsequently challenge the age-old theory of "East to West" spread of venereal syphilis. This contribution warrants the continuation of study in this direction, taking into account skeletal studies that utilized radiocarbon dating technique and the phylogenetic analysis of the bacterial strains, offering a possible consensus on the origin and evolution of syphilis. PMID- 22324171 TI - A new paradigm in the treatment of kerions: treat the inflammation. AB - Kerions result from a massive delayed-type hypersensitivity reaction to a dermatophyte. Treatment traditionally has been directed primarily toward the dermatophyte. The authors propose, however, that inflammation should be the initial target oftreatment. Clinical findings and treatment outcomes for two patients with kerions, treated with short courses of anti-inflammatory agents, are presented. Earlier studies showing minimal effects with corticosteroid treatment of kerions may have had design flaws. The anti-inflammatory treatment of kerions is both safe and effective and permits the duration of therapy to be shortened dramatically. PMID- 22324172 TI - Pityriasis rubra pilaris: evolution of challenges in promising treatment options. AB - Pityriasis rubra pilaris is an uncommon inflammatory dermatosis that is well recognized across the globe. Erythroderma is a common presentation. A precise diagnosis of pityriasis rubra pilaris is based on morphologic features and is classified into 6 types: classic adult onset (type I), atypical adult (type II), classic juvenile (type III), circumscribed juvenile (type IV), atypical juvenile (type V), and human immunodeficiency virus-associated (type VI). Several conventional systemic and/or topical treatments are currently in use. Largely, their results are unsatisfactory and limited by long-term toxicity. The authors investigate the efficacy of a wide spectrum of drugs by examining historical (archive) and promising (modern) treatment modalities for the treatment of pityriasis rubra pilaris. PMID- 22324173 TI - The role of surgical debridement in healing of diabetic foot ulcers. AB - A critical question in the treatment of chronic wounds is whether and when debridement is needed. The three most common chronic wounds are the diabetic foot ulcer (DFU), the venous leg ulcer, and the pressure or decubitus ulcer. Surgical debridement, aimed at removing necrotic, devitalized wound bed and wound edge tissue that inhibits healing, is a longstanding standard of care for the treatment of chronic, nonhealing wounds. Debridement encourages healing by converting a chronic nonhealing wound environment into a more responsive acute healing environment. While the rationale for debridement seems logical, the evidence to support its use in enhancing healing is scarce. Currently, there is more evidence in the literature for debridement for DFUs than for venous ulcers and pressure ulcers; however, the studies on which clinicians have based their rationale for debridement in DFUs possess methodologic flaws, small sample sizes, and bias. Thus, further studies are needed to develop clinical evidence for its inclusion in treatment protocols for chronic wounds. Here, the authors review the scientific evidence for debridement of DFUs, the rationale for debridement of DFUs, and the insufficient data supporting debridement for venous ulcers and pressure ulcers. PMID- 22324174 TI - Cutaneous tuberculosis: a diagnostic dilemma. AB - Cutaneous tuberculosis continues to be one of the most difficult conditions to diagnose. It is a challenge particularly in developing countries due to the lack of resources. The authors define the classification and clinical manifestations considered predictive of its diagnosis. PMID- 22324175 TI - Repelling insects with safe and effective alternatives to DEET. PMID- 22324176 TI - It's not just who you are, it's also where you are: the cutaneous leiomyosarcoma dilemma. PMID- 22324177 TI - It may be vulgar, but it isn't a bad word. PMID- 22324178 TI - Unusually severe case of dermatosis neglecta. AB - An 18-year-old black woman with cerebral palsy was admitted for evaluation of an intrathecal baclofen pump site infection. The dermatology service was consulted for treatment suggestions of a presumed diagnosis of chronic tinea capitis. Three courses of oral griseofulvin during the past 2 years failed to resolve the patient's chronic scalp dermatosis. Scalp lesions first began about 2 years earlier after hospitalization for placement of an intrathecal baclofen pump. The patient was unable to care for her scalp due to her cerebral palsy, and her mother interpreted the scalp condition as infectious. No routine shampoo care, scalp care, or topical treatment was performed for more than 1 1/2 years. The mother felt that touching the patient's scalp might cause pain and noted that the majority of her time was spent concentrating on more critical medical issues. Physical examination revealed coalescing hyperkeratotic plaques extending dorsally from the anterior hairline to the occipital scalp with small flecks of keratinous debris throughout the remaining hair (Figure 1). The plate-like plaques were devoid of hair, except at a few fissures where a few tufts of hair emerged. No cervical lymph nodes were appreciated on palpation. Treatment was initiated with compresses consisting of large warm water-soaked towels 4 times daily. Three times a day, a nursing staff applied 5% salicylic acid in olive oil to the scalp under a shower cap for approximately 1 hour. Over the following 2 days, a significant reduction in keratinous debris was appreciated. Within 2 weeks, the bulk of the plaques had been removed (Figure 2). At 6-week follow-up, the underlying scalp showed areas of fibrosis and possible scarring with a few emerging tufts of hair. On the basis of history and response to treatment with salicylic acid and routine scalp care, the patient was diagnosed with an unusually severe case of dermatosis neglecta. PMID- 22324179 TI - Fixed-drug eruption caused by ashwagandha (Withania somnifera): a widely used Ayurvedic drug. AB - A 28-year-old man with decreased libido received ashwagandha in the usual daily dosage of 5 g for 10 days. During this period, he experienced a burning and/or itching sensation as well as discoloration of the skin/mucous membrane confined to the penis. He had a similar type of eruption at the same site 6 months prior while taking ashwagandha. Examination of the skin surface was conspicuous and marked by the presence of a dusky, erythematous, oval, eroded plaque of 3 cm, affecting the glans penis and prepuce (Figure). The drug was withdrawn and topical 0.05% clobetasol propionate cream was administered along with cetrizine dihydrochloride, an H1-receptor blocker, 10 mg daily for 1 month. There was a perceptible amelioration of the lesion, resulting in residual greyish white pigmentation. He was prescribed oral drug provocation with 1 g of ashwagandha powder. Within 12 hours, a flare-up developed at the earlier site, confirming the causality. PMID- 22324180 TI - Chronic lymphocytic leukemia revealed by a branulomatous zosteriform eruption. AB - A 70-year-old woman presented with an atypical erythematopapular zosteriform eruption of 3 weeks' duration. The patient had no history of previous vesicular eruption. She developed a painful burning sensation on the neck. Clinical examination revealed a cluster of small erythematous firm papules and plaques in a zosteriform distribution on the left ear, face, neck, and shoulder (Figure 1A). The lesions were unilateral and did not cross the midline. Multiple cervical and axillary lymph nodes were palpable. Laboratory tests revealed an increase in white blood cells of 25,000/mm3, with 17,910/mm3 lymphocytes and a normal range of hemoglobin, platelets, creatinine, and liver enzymes. Erythrocyte sedimentation rate was 87 mm. Blood smear results showed small, morphologically mature lymphocyte cells. In immune phenotyping, lymphocyte cells co-express CD5 and B-cell-surface antigens CD19 and CD23, as well as a restriction of kappa immunoglobulin light chains. The cells were CD22-, CD79b-, CD38-, CD10-, CD25- and FMC7-. Computed thoracoabominal tomography revealed cervical, mediastinal, abdominal, and pelvic adenopathy confirming the diagnosis of B-cell chronic lymphocytic leukemia (B-CLL) stage B. Histology of a skin biopsy from a papule showed a dense nodular granulomatous infiltrate in the dermis (Figure 2A). The infiltrate contained epithelioid and giant cells surrounded by lymphocytes and plasma cells. Small monomorphic lymphocytes without mitotic figures predominated (Figure 2B). The epidermis was irregularly thickened. Immunohistology revealed a polymorphous infiltrate with a phenotype of reactive T lymphocytes (CD3, CD5 positive) (Figure 2C), B lymphocytes (CD20 positive) (Figure 2D). Epithelioid and giant cells were positive for CD68 (Figure 2E). A latent herpes zoster infection with granulomatous reaction at the site ofzoster lesions was highly suspected as the patient reported a unilateral burning sensation without a history of vesicular zosteriform eruption. She received treatment with intravenous acyclovir 10 mg/kg every 8 hours. The papular lesions resolved markedly (60%) on macular plaques at the end of the treatment. Following topical treatment with corticosteroids, the lesions healed completely within 4 weeks (Figure 1B). Concerning leukemia, our patient was monitored without therapy by the hematologist. PMID- 22324181 TI - Mycobacterium marinum cutaneous infection with sporotrichoid distribution treated with azithromycin monotherapy. PMID- 22324182 TI - [Systemic-psychomotoric versus purely verbal systemic counselling in families of children with mental disorders]. AB - Systemic counselling and therapy are usually verbal interventions. However, communication on an abstract level often exceeds the capabilities of children up to about 12 years, leaving them less involved in the therapeutic process. In contrast, symbolic play has been shown to be an effective tool for psychological formulation and intervention. However, it has not been widely used so far in family therapy. In order to explore this hypothesis a form of systemic family therapy (SB; exclusively verbal) was compared with a new concept called systemic psychomotor family counselling (PsyFam; based on symbolic play). We found good efficacy of PsyFam, reflected in an average effect size of d = .73 (SB: d = .53), even though statistical significance of the group effect could not be shown due to the small sample size. Systemic-psychomotoric family counselling is a promising new approach worth further research in controlled therapy studies. PMID- 22324183 TI - [Assessment of cognitive abilities of mentally retarded children: applying the Kaufman-Assessment Battery for Children (K-ABC) with children with Down's syndrome]. AB - Standardized tests only give limited information on the intellectual competencies of children with learning difficulties due to problems such as the "floor effect", poor differentiation in the lower range of functioning and flat profiles. Therefore, Reynolds and Clark (1985) suggested supplementing the standard analysis on the basis of chronological age with an alternative form of analysis on the basis of the developmental age level. The present study compares both forms of analysis for a group of 15 children with Down's syndrome tested with the Kaufman-Assessment Battery for Children (K-ABC). The standardized analysis resulted in flat profiles in the lowest range, showing little difference within and between the children. On the other hand, the alternative analysis demonstrated a high variability with a number of individual strengths and weaknesses as well as trends for this group of children. While the standardized analysis allows the determination of the level of intellectual capability, the determination of individual strengths and weaknesses through the alternative analysis can be an important basis for individualized training and therapy. PMID- 22324184 TI - [The German version of the "Screen for Child Anxiety Related Emotional Disorders" (SCARED): parent- and self report in a clinical sample]. AB - The psychometric properties and cross-informant agreement of the German version of the "Screen for Child Anxiety Related Emotional Disorders" (SCARED) were assessed in a clinical sample. 77 children and adolescents aged 11 to 18 years in outpatient psychotherapy and 66 parents filled out the SCARED and Youth Self Report (YSR) or Child Behavior Checklist (CBCL), respectively. In n = 57 cases both parent and self-report was available. The German SCARED is shown to have good convergent and divergent validity compared with YSR/CBCL scales. The total score discriminated between children with an anxiety disorder and children with another psychiatric disorder. Cross-informant agreement was moderate with children reporting more and more severe anxiety symptoms than their parents. In conclusion, both the parent and the child version of the German SCARED proved valid. In clinical settings the integration of data from both perspectives seems important. PMID- 22324185 TI - ["Nobody talks to me"--a case-study of group bullying in school]. AB - If there is group bullying in a school-class, interventions should be set fast and convincingly. A variety of interventions against group bullying are available in the literature. The following case-study focuses on the analysis of the conflicts and dynamics between the different representatives in a concrete group bullying-situation and describes the use of counter-transference as a way to understand the process and to choose effective interventions. Suggestions on handling typical group bullying-situations are added and aim at a concept of counselling that connects reflection and active intervention in tandem as a valid method of management. PMID- 22324186 TI - Designing education to improve care. AB - BACKGROUND: Educators in all health care disciplines are increasingly aware of the importance and value of teaching improvement as an integral part of health professional development. Although faculty and learners can often identify needed changes in the clinical setting, many educators are not sure how to teach the improvement principles and methods needed to achieve and sustain those changes. DEFINING AND DEVELOPING COMPETENCY IN QI: Five developmental levels apply to physicians, nurses, and other members of an interprofessional quality improvement (QI) team: novice, advanced beginner, competent, proficient, and expert. For example, the expert develops a vast repertoire of skills and a capacity for situational discrimination, performs tasks on a more intuitive level, and recognizes and immediately addresses essential problems. Improvement is an action, and learning about improvement must be action based. Certain skills and knowledge are required at each stage in this learning process so that students in the health professions achieve competence in QI before entering practice. GENERAL PRINCIPLES FOR EDUCATIONAL EXPERIENCES IN HEALTH CARE IMPROVEMENT: Four principles, which apply at any developmental level, can help answer educators' questions about where to start: (1) The Learning Experience Should Be a Combination of Didactic and Project-Based Work; (2) Link with Health System Improvement Efforts; (3) Assess Education Outcomes; and (4) Role Model QI in Educational Processes. CONCLUSION: As educators teach future health professionals about improving care, the dissemination of exemplary models and emerging best practices will be increasingly important. Sustainability of improvements in patient outcomes will be dependent on both the value systems and skills of health professionals entering practice. PMID- 22324187 TI - Using information technology to improve adult immunization delivery in an integrated urban health system. AB - BACKGROUND: Adult immunizations prevent morbidity and mortality yet coverage remains suboptimal, in part due to missed opportunities. Clinical decision support systems (CDSSs) can improve immunization rates when integrated into routine work flow, implemented wherever care is delivered, and used by staff who can act on the recommendation. METHODS: An adult immunization improvement project was undertaken in a large integrated, safety-net health care system. A CDSS was developed to query patient records and identify patients eligible for pneumococcal, influenza, or tetanus immunization and then generate a statement that recommends immunization or indicates a previous refusal. A new agency policy authorized medical assistants and nurses in clinics, and nurses in the hospital, to use the CDSS as a standing order. Immunization delivery work flow was standardized, and staff received feedback on immunization rates. RESULTS: The CDSS identified more patients than a typical paper standing order and can be easily modified to incorporate changes in vaccine indications. The intervention led to a 10% improvement in immunization rates in adults 65 years of age or older and in younger adults with diabetes or chronic obstructive pulmonary disease. Overall, the improvements were sustained beyond the project period. The CDSS was expanded to encompass additional vaccines. CONCLUSIONS: Interdepartmental collaboration was critical to identify needs, challenges, and solutions. Implementing the standing order policy in clinics and the hospital usually allowed immunizations to be taken out of the hands of clinicians. As an on-demand tool, CDSS must be used at each patient encounter to avoid missed opportunities. Staff retraining accompanied by ongoing assessment of immunization rates, work flow, and missed opportunities to immunize patients are critical to sustain and enhance improvements. PMID- 22324188 TI - A review of verbal order policies in acute care hospitals. AB - BACKGROUND: Although verbal and telephone orders (VOs) are commonly used in the patient care process, there has been little examination of the strategies and tactics used to ensure their appropriate use or how to ensure that they are accurately communicated, correctly understood, initially documented, and subsequently transcribed into the medical record and ultimately carried out as intended. A systematic review was conducted of hospital verbal and telephone order policies in acute care settings. METHODS: A stratified random sample of hospital verbal and telephone order policy documents were abstracted from critical access, rural, rural referral, and urban hospitals located in Iowa and Missouri and from academic medical centers from across the United States. FINDINGS: Substantial differences were found across 40 acute care settings in terms of who is authorized to give (including nonlicensed personnel) and take VOs and in terms of time allowed for the prescriber to cosign the VO. When a nonphysician or other licensed prescriber was allowed to communicate VOs, there was no discussion of the process to review the VO before it was communicated in turn to the hospital personnel receiving the order. Policies within several of the same hospitals were inconsistent in terms of the periods specified for prescriber cosignature. Few hospitals required authentication of the identity of the person making telephone VOs, nor the use of practices to improve communication reliability. CONCLUSION: Careful review and updating of hospital VO policies is necessary to ensure that they are internally consistent and optimize patient safety. The implementation of computerized medical records and ordering systems can reduce but not eliminate the need for VOs. PMID- 22324189 TI - Secondary uses of electronic health record data: benefits and barriers. AB - In the primary use of health data, patient health information in electronic health records (EHRs) directly informs each individual's care. In secondary use, patient data would be aggregated to improve health care delivery, yet several technological and policy barriers may slow implementation-but may be amenable to intervention. PMID- 22324190 TI - Using the Opportunity Estimator tool to improve engagement in a quality and safety intervention. AB - Teams throughout the United States participating in a program to reduce central line-associated bloodstream infections (CLABSIs) are using the Opportunity Estimator. This web-based tool translates CLABSI-related data into "opportunity estimates" of the patient lives and money that could be saved by reducing these infections. PMID- 22324191 TI - From the strength of many, the power of one. PMID- 22324192 TI - Title is just one factor in determining compensation. PMID- 22324193 TI - Building trust boosts business results. PMID- 22324194 TI - Physician compensation: are you checking the right box? PMID- 22324195 TI - Practice takes tragedy to heart. PMID- 22324196 TI - To integrate or not? PMID- 22324197 TI - Now you know your ACOs. PMID- 22324198 TI - Leadership a common denominator for MGMA-ACMPE award winners. PMID- 22324199 TI - New frontiers. PMID- 22324200 TI - What's your strategy? PMID- 22324201 TI - The depravity of the youth. 1907. PMID- 22324202 TI - Isolated elders and precocious children. PMID- 22324203 TI - An analysis of elder abuse rates in Milwaukee County. AB - INTRODUCTION: The elder abuse and neglect burden in Milwaukee County, Wisconsin, is substantial, with 3384 reports made from 2006 to 2009. Current prevalence estimates are determined from reported cases only and are likely underestimated. Provider awareness of victim and perpetrator characteristics is necessary to increase recognition and response. METHODS: A cross-sectional analysis of elder abuse and neglect cases reported to the Milwaukee County Department on Aging (MCDA) from 2006 to 2009 was performed to provide a profile of the county's elder abuse burden by victim, perpetrator, and reporter characteristics. Annual reporting trends were identified using Poisson regression analysis. RESULTS: Fifty-eight percent of MCDA reports of abuse were substantiated after investigation. Victims in Milwaukee County tended to be older than 75 (64%), female (64%), and white (62%). Reporting rates to the MCDA were significantly lower in 2009 than 2006. Perpetrators were often adult children (48%) or a spouse (14%). Forty percent of life-threatening cases of self-neglect were due to unfulfilled medical needs. Most reports were made by medical professionals (23%), relatives of the victim (21%), and community agencies (18%). Only 13% of elder abuse victims were placed in nursing homes and assisted living centers; many received services to assist independent living. DISCUSSION: Although this study is limited to reported cases only, it provides a valuable profile of pertinent elder abuse characteristics in Milwaukee County. CONCLUSION: Characteristics of vulnerable elders, potential abusers, and investigation outcomes are described to inform clinical practice about this important social issue. PMID- 22324204 TI - A retrospective study of the natural history of endogenous subclinical hyperthyroidism. AB - OBJECTIVE: The treatment of subclinical hyperthyroidism is controversial because the natural history is uncertain. We undertook a retrospective study to examine the natural history of endogenous subclinical hyperthyroidism. METHODS: Between 2002 and 2006, we identified 116 patients with thyroid-stimulating hormone (TSH) concentrations <0.4 microIU/mL but normal free thyroxin and triiodothyronine or free triiodothyronine levels and >6 months of follow-up. The medical records of these subclinical hyperthyroid patients were reviewed for demographic data, clinical outcomes, and thyroid function test results. Because the etiology of hyperthyroidism could not be identified in 57 (49%) patients, we compared patients with normal-sized or diffusely enlarged thyroid glands with patients with nodular thyroid glands. We also compared the results of patients with initial TSH levels <0.1 microIU/mL to patients with TSH levels between 0.1 and 0.39 microIU/mL, and patients age <65 years to older patients. RESULTS: Of 116 patients with subclinical hyperthyroidism, 88 (76%) were women and 28 (24%) were men. They ranged in age from 19 to 98 years (mean = 55 years). Ninety-eight patients did not have thyroid nodules, and 18 had thyroid nodules. Follow-up ranged from 6 months to 6.5 years (median, 3.2 years). TSH reverted to normal in 58 (59%) patients without nodules; we treated only 4 (4%) of these patients for hyperthyroidism. In contrast, TSH levels in only 3 (17%) patients with nodules reverted to normal and 7 (39%) received antithyroid treatment. Atrial fibrillation was present in 8 (8%) patients without thyroid nodules and in 3 patients (17%) with thyroid nodules (P=.373). There were no significant outcome differences based on initial TSH levels or age. CONCLUSION: We conclude that most patients with subclinical hyperthyroidism who do not have thyroid nodules rarely require antithyroid therapy but should be followed carefully. PMID- 22324205 TI - Hyperlexia III: separating 'autistic-like' behaviors from autistic disorder; assessing children who read early or speak late. AB - Three conditions -- Hyperlexia (children who read early), Einstein syndrome (children who speak late), and "Blindisms" (in children with impaired vision) -- can present with "autistic-like" symptoms, traits, and behaviors that need to be differentiated from autistic disorder. Careful attention to that critical difference has important epidemiologic, etiologic, treatment, and outcome implications. This paper describes these conditions, makes suggestions for proper identification that can prevent unnecessary worry and distress for parents and other caregivers, and suggests appropriate management. PMID- 22324206 TI - Acute transient sensorineural hearing loss due to Anaplasma phagocytophilum. AB - We report the case of a patient who presented with a 3-month history of random epistaxis and recent onset of acute hearing loss associated with fever, chills, and myalgias. Pure tone audiometry revealed bilateral sensorineural hearing loss. Complete blood cell count showed an abnormal neutrophil count of 700/uL (normal >1900/microL) and platelet count of 25 x 10(3)/microL (normal >175 x 10(3)/microL). Giemsa-stained peripheral blood smear revealed neutrophilic intracytoplasmic inclusion consistent with anaplasma morulae. Polymerase chain reaction confirmed Anaplasma phagocytophilum. The patient was treated with oral doxycycline, and, after 14 days of treatment, the hearing loss had improved markedly. Therefore, we concluded that the patient's acute transient bilateral sensorineural hearing loss was associated with anaplasmosis. PMID- 22324207 TI - A report of 2 cases of myopericarditis after Vaccinia virus (smallpox) immunization. AB - BACKGROUND: To counter the possibility of smallpox being used as a biological weapon, in 2002 the US government restarted a smallpox vaccination campaign. Myopericarditis is a possible cardiac complication of smallpox vaccination. We report 2 cases of vaccine-associated myopericarditis in military recruits who were treated at our facility. Chest pain, shortness of breath, and electrocardiographic changes of pericarditis, with a recent history of smallpox vaccination, were useful in making the diagnosis of probable post-vaccinial myopericarditis. Nonsteroidal, anti-inflammatory drugs (NSAIDs) were used to manage myopericarditis. Both patients had complete resolution of symptoms and electrocardiographic changes and subsequently returned to active duty. CONCLUSION: Myopericarditis should be suspected when patients with recent history of smallpox vaccination present with chest pain or shortness of breath. Nonsteroidal anti-inflammatory drugs are useful in the management of post vaccinial myopericarditis. PMID- 22324208 TI - What every physician needs to know to prepare for ICD-10. PMID- 22324209 TI - Concealed carry: best practices after November 1, 2011. PMID- 22324210 TI - UW Tobacco Research and Intervention Center making a difference. PMID- 22324211 TI - How mediation (and other) approaches may improve ethics consultants' outcomes. AB - Articles in this issue of JCE recommend a number of approaches to clinical ethics consultation. Given these various approaches, how should ethics consultants proceed? PMID- 22324212 TI - Consensus, clinical decision making, and unsettled cases. AB - The model of clinical ethics consultation (CEC) defended in the ASBH Core Competencies report has gained significant traction among scholars and healthcare providers. On this model, the aim of CEC is to facilitate deliberative reflection and thereby resolve conflicts and clarify value uncertainty by invoking and pursuing a process of consensus building. It is central to the model that the facilitated consensus falls within a range of allowable options, defined by societal values: prevailing legal requirements, widely endorsed organizational policies, and professional standards of practice and codes of conduct. Moreover, the model stipulates that ethics consultants must refrain from giving substantive recommendations regarding how parties to a moral disagreement in the clinic should evaluate their options. We argue that this model of CEC is incomplete, because it wrongly assumes that what counts as the proper set of allowable options among which the parties are to deliberate will itself always be clearly discernible. We illustrate this problem with a recent case on which one of us consulted-a neonate born with trisomy 18 (T18). We try to show that law, policy, and standards of practice reveal no clear answer to the question posed by the case: namely, whether forgoing gastrostomy tube feedings for a baby with T18 is allowable. We suggest there may be other kinds of cases in which it may simply be unsettled whether a given choice falls within the set of allowable options within which consensus is to be facilitated. What should an ethicist do when confronting such unsettled cases? We agree with the facilitation model that an ethicist should remain neutral among the allowable options, when it is clear what the allowable options are. But, in unsettled cases, the role of a consultant should be expanded to include a process of moral inquiry into what the allowable options should be. We end by raising the issue of whether this means an ethicist should share his or her own conclusions or views about the allowability of a given clinical option. PMID- 22324213 TI - The role of the clinical ethics consultant in "unsettled" cases. AB - In this article I take up a central question posed by the article jointly authored with Bill Winslade in this issue of JCE: What should be the role of clinical ethics consultants (CECs) in (what we call) an unsettled case: that is, a situation in which the range of allowable choices, among which the parties to a bioethical disagreement must select, cannot be clearly or completely specified? I argue here that CECs should, in such cases, guide the parties by presenting their own reasoned conclusions about what the scope of allowable choices should be taken to include. Since this position challenges the received view that CECs must not express their own moral positions or conclusions in their role as ethicists, I try to defend my view of the CEC's role in unsettled cases against several objections. PMID- 22324214 TI - Confronting ambiguity: identifying options for infants with trisomy 18. AB - Identifying ethically allowable options for infants with trisomy 18 has become more challenging as medical standards of practice shift, based on emerging scientific data and changing societal perceptions of disability. Lack of a stable professional standard of practice ought not prevent ethicists from facilitating a consensus; rather, these "unsettled cases" require an individualized, narrative approach that allows the values of the family and the particularities of each case to provide the necessary additional moral grounding. PMID- 22324215 TI - "Facilitated consensus," "ethics facilitation," and unsettled cases. AB - In "Consensus, Clinical Decision Making, and Unsettled Cases:' David M. Adams and William J.Winslade' make multiple references to both editions of the American Society of Bioethics and Humanities (ASBH) Core Competencies for Healthcare Ethics Consultation in their discussion of two assumptions that are supposed to be at the heart of the facilitated consensus model's inability to handle unsettled cases; that is, that: 1. Consultants "should maintain a kind of moral impartiality or neutrality throughout the process," "explicitly condemn[ing] anything resembling a substantive 'ethics' recommendation, and 2. "What counts as the proper set of allowable options among which the parties are to deliberate will itself always be clearly discernible' Herein, I argue that neither of these assumptions is required by ASBH's ethics facilitation approach. I then conclude by suggesting that, despite their fundamentally mistaken interpretation of the ASBH approach-perhaps even because of it-Adams and Winslade have made two important contributions to the ethics consultation literature. PMID- 22324216 TI - Commentary on "Consensus, clinical decision making, and unsettled cases". AB - Ethics consultation, while often a process of negotiation between diverse opinions, sometimes requires deeper moral inquiry. The form of such inquiry is suggested by classical casuistry and its attendant doctrine of probabilism. PMID- 22324217 TI - Ill-placed democracy: ethics consultations and the moral status of voting. AB - As groups around the country begin to craft standards for clinical ethics consultations, one focus of that work is the proper procedure for conducting ethics consults. From a recent empirical look into the workings of ethics consult services (ECSs), one worrisome finding is that some ECSs rely on a committee vote when making a recommendation. This article examines the practice of voting and its moral standing as a procedural strategy for arriving at a clinical ethics recommendation. I focus here on the type of clinical ethics conflicts that are most likely to lead an ECS to vote, namely, conflicts involving ethical uncertainty--or, in the Greek, aporia. I argue that in cases of aporia, voting on an ethics conflict is not a morally justifiable procedure. Then on the same grounds that I use to show that voting is ethically problematic, I raise broader concerns about the common practice of making recommendations by other procedures. In contrast to the standard approach of adjudicating between moral claims, I argue that ECSs can best resolve aporetic conflict through the process of clinical ethics mediation. PMID- 22324218 TI - Commentary on Fiester's "Ill-placed democracy: ethics consultations and the moral status of voting". AB - Autumn Fiester identifies an important element in clinical ethics consultation (CEC) that she labels, from the Greek, aporia, "state of perplexity," evidenced in CEC as ethical ambiguity. Fiester argues that the inherent difficulties of cases so characterized render them inappropriate for voting and more amenable to mediation and the search for consensus. This commentary supports Fiester's analysis and adds additional reasons for rejecting voting as a process for resolving disputes in CEC including: it distorts the analysis by empowering individual voters preferences and biases rather than focusing on the interests and wishes of the patient and family; it offers an insufficiently sensitive model for resolving the awesome, nuanced, conflicted, and ethically complex issues surrounding life and death; it marginalizes minority opinions that may have moral validity. PMID- 22324219 TI - Clinical ethics consultation's dilemma, and a solution. AB - Clinical ethics consultation is on the horns of a dilemma. One horn skewers the field for its lack of standards, while the other horn skewers it for proposing arbitrary or deeply contested foundations. I articulate the dilemma by discussing several critiques of the field and the challenge of formulating standards and suggest that the solution lies, at least until a robust consensus emerges, with establishing a list of proscriptive standards to guide the field. PMID- 22324220 TI - More room in the store-room. PMID- 22324221 TI - A novel method for evaluating periodontal recession: a feasibility study. AB - PURPOSE: To evaluate whether a three-dimensional (3D) optical method currently used for the production of dental restorations could be applied to the simultaneous evaluation of the height and width of periodontal recessions, and determine the reproducibility and accuracy of the method for evaluating periodontal recession. MATERIALS AND METHODS: The height and width of periodontal recessions scratched onto stone replicas were recorded using a 3D optical method, a periodontal probe, and a caliper. RESULTS: No difference was found between measurements obtained using the methods tested (p > 0.05). However, measurements using the 3D optical method showed the highest reproducibility. CONCLUSION: The 3D optical method allowed the accurate and reproducible evaluation of the height and width of periodontal recessions. The next step should be the development of fully automated soft-tissue monitoring software to increase time savings. PMID- 22324222 TI - Tensile bond strength of ceramic crowns to dentin using resin cements. AB - PURPOSE: This study measured the bond strength of the self-adhesive resin cements and a bonded resin cement for crowns bonded to extracted teeth with preparations having a total taper greater than 30 degrees. A crown pull-off test was used with direction of pull along the path of insertion. The CAD/CAM system Cerec was used to create crowns with the pull-off loop as an integral part of the crown structure. MATERIALS AND METHODS: One hundred extracted human molars were prepared for all-ceramic crowns with a 1.5-mm shoulder, greater than 30-degree axial wall convergence, a flat occlusal surface and 3 to 5 mm occlusal/ gingival height. All-ceramic crowns were cemented with five different self-adhesive cements (Rely X Unicem, Maxcem Elite, BisCem, SmartCem 2, and G-Cem) and one bonded resin cement (Multilink). Forfour cements (excluding GCem and Multilink) there were 2 groups, one with HF etching and one without ceramic surface treatment. The crowns were then subject to tensile stress until either the crown fractured or the crown was lifted off from the tooth. RESULTS: For several cements, the bond strength exceeded the tensile strength of the all-ceramic crown; thus, the crown fractured, leaving the cemented part of the crown on the tooth. The effect of ceramic surface etching was not statistically significant at p = 0.05; however, for each cement, the treated crowns showed a lower coefficient of variance (COV). For this study, the COV ranged from 24.9 % to 97.9 %. Loads ranged from 41.3 to 190.3 N. CONCLUSION: Some of the new self-etching resin cements can create bonds to non-retentive crown preparations that are stronger than the strength of a ceramic crown; however, these high bond strengths may not be able to be achieved consistently. PMID- 22324223 TI - Diagnostic ability of computed tomography using DentaScan software in endodontics: case reports. AB - Radiographic examination is essential in diagnosis and treatment planning in endodontics. Conventional radiographs depict structures in two dimensions only. The ability to assess the area of interest in three dimensions is advantageous. Computed tomography is an imaging technique which produces three-dimensional images of an object by taking a series of two-dimensional sectional X-ray images. DentaScan is a computed tomography software program that allows the mandible and maxilla to be imaged in three planes: axial, panoramic, and cross-sectional. As computed tomography is used in endodontics, DentaScan can play a wider role in endodontic diagnosis. It provides valuable information in the assessment of the morphology of the root canal, diagnosis of root fractures, internal and external resorptions, pre-operative assessment of anatomic structures etc. The aim of this article is to explore the clinical usefulness of computed tomography and DentaScan in endodontic diagnosis, through a series of four cases of different endodontic problems. PMID- 22324224 TI - Chairside CAD/CAM templates for implantology. PMID- 22324225 TI - Digital veneering 2 -- fabrication of CAD/ CAM veneer structures with Rapid Layer Technology. PMID- 22324226 TI - 12th international ISCD Certified Cerec Trainers Course in Vancouver. PMID- 22324227 TI - The profession has plenty to be proud of. PMID- 22324229 TI - Regional pay variation in the NHS could be in place as soon as 2013. PMID- 22324228 TI - More strikes likely after unions denounce 'divisive' pension offer. PMID- 22324230 TI - Every NHS trust urged to take up the challenge of improving care. PMID- 22324231 TI - Government refuses to set a time limit on criminal records checks. PMID- 22324232 TI - Nursing in 2011: the campaigns, people and political debates. PMID- 22324233 TI - Lights, camera, A&E. AB - Channel 4 series 24 Hours in A&E was one of the television highlights of 2011. Filmed at King's College Hospital in London, it showed the reality of life in an A&E department and may have improved the public's understanding of nursing. PMID- 22324234 TI - Hard to stomach. AB - There is clear evidence that poor diet and obesity are a major cause of the worldwide epidemic of non-communicable diseases such as heart disease, cancer and stroke. Action is needed to make it easier for people to make healthy choices and access effective weight management programmes. PMID- 22324235 TI - Time for a change. AB - With the help of a leading European image consultancy, Nursing Standard gave two readers a professional makeover to boost their confidence and help them make a better impression in their daily lives. PMID- 22324236 TI - Introduction of mealtime volunteers in a district general hospital. AB - This article describes the introduction of volunteers in a small district general hospital to assist patients with their meals. Training provided to prospective volunteers, the introduction of mealtime volunteers to the wards and their effect on patients' mealtime experience are outlined. The article also discusses issues that arose during this process, how these issues were resolved and plans to expand the service in the future. PMID- 22324237 TI - An evaluation of sharp safety intravenous cannula devices. AB - This article describes an evaluation of seven sharp safety intravenous (IV) cannula devices in six Welsh NHS hospitals and the Welsh Ambulance Service. Products analysed included six passive devices designed to engage the safety feature automatically on withdrawal of the needle from the cannula and one active device that requires a button to be pressed to activate it. The companies concerned provided the devices and appropriate training. Participating healthcare workers used the safety device instead of the conventional device to perform IV cannulations during the evaluation and each type of device was evaluated in random order Participants filled in a questionnaire for each device and then a further questionnaire comparing each one at the end of the process. Results showed that two of the passive devices were the most preferred. Most users stated that they would use either of these devices instead of the conventional device. It was not possible to identify a favourite between these two devices. Some devices were considered to be unfavourable. The main disadvantages that users experienced included slow flashback (where venepuncture is confirmed by blood visibly entering the device), blood leakage from the back of the device and resistance when withdrawing the needle from the cannula. PMID- 22324238 TI - Skill analysis part 1: defining and implementing a practice skill. AB - This is the first of three articles exploring skill analysis, assisting readers to select and describe a practice skill of their choice. The aim is to help the nurse to proceed in a stepwise fashion, to understand what comprises the skill and what is important as the skill is put into action. It is anticipated that readers will make varying progress in this work. Some will analyse their skill with considerable confidence, others much more tentatively. However, first insights are important and valuable. In subsequent articles, the reader is assisted to evaluate the chosen skill and then make plans for its improvement. The most valuable aspect of this series is the understanding of the skill analysis process as a means to focus reflective practice. PMID- 22324239 TI - MRSA in hospitals. PMID- 22324240 TI - Care forecasters. PMID- 22324241 TI - Have you got what it takes? PMID- 22324242 TI - Learn from the best. PMID- 22324243 TI - Sixty years of research of tick-borne encephalitis--a basis of the current knowledge of the epidemiological situation in Central Europe. AB - Tick-borne encephalitis (TBE) virus was isolated for the first time in Central Europe in 1948 from both a patient and Ixodes ricinus ticks collected in the area where the patient had been tick bitten (the Beroun area - Central Bohemia) and concomitantly from a TBE patient in Moravia (the Vyskov area). Another priority discovery was alimentary transmission of TBE virus via the milk from tick infected grazing goats that was made during a TBE outbreak in Roznava (SE Slovakia). This outbreak of 660 cases has been the largest of its kind. Both of these discoveries were a challenge to multidisciplinary research into the natural focality of TBE. The results obtained were published by Czech and Slovak authors in the first European TBE monograph (1954) and were the stimulus for further research in this area. From the epidemiological point of view, among others, the impact of meteorological factors (on TBE incidence associated with I. ricinus host-seeking activity) and recreational nature of TBE were clearly defined then. At the same time, TBE became a notifiable disease (since 1971 laboratory confirmed TBE cases only). In the following decades, the phenomenon of natural focality of TBE (including anthropic impacts) was extensively studied and the determinants of high-risk areas in the field were analyzed. The results were used in the creation of I. ricinus and TBE risk prediction maps for the Czech Republic generated for the first time in Europe using LANDSAT 5 satellite data and GIS technology (1990). In the early 1990s (in particular since 1993), similarly to other countries, the Czech Republic reported a sharp rise in TBE cases that continues, with some fluctuations, until now. The cooperation with climatologists in the analysis of historical data, current epidemiological observations, and study of I. ricinus in the field have shown a decisive impact of the ongoing climate change. The analysis of the socio-economic conditions in high-risk areas for TBE has not revealed any impact of these conditions on TBE morbidity. The recreational factor that is influenced by the weather changes has a considerable impact. The seasonal trend of TBE cases shows large fluctuations as were seen in 2006, 2009, and 2010, also as a result of weather changes with seasons. This clearly implies the need for using long time series of data, covering at least a decade, to be able to draw general conclusions as is the case in the present study (2001-2010). The data broken down by Administrative Region display substantial interregional differences. Of 14 Administrative Regions of the Czech Republic, three exhibits a linear trend in TBE incidence, with a minimum deviation from the baseline, four Regions show different downward linear trends, but seven Regions display different upward trends. The upward trend is most obvious in the Highlands (Vysocina) Region where it is associated with the prevalent orographic conditions and increase in the incidence of I. ricinus ticks at higher altitudes. The knowledge of the area where the patient was tick bitten that is entered in the Epidat database as the "probable area of TBE infection acquisition" is helpful in identifying high-risk areas for TBE. By matching the area of TBE acquisition with that of the patient's domicile we revealed that TBE patients had to travel to areas other than their area of domicile to acquire TBE and thus also significance of the areas of TBE acquisition at the country level. The population of the Prague Region (NUTS3 CZ010) can be used as an illustrative example, with 37.7% of TBE cases only reported to be acquired in the Prague Region while 33.4% of TBE cases were associated with travel to the Central Bohemian Region and 13.9% of TBE cases were imported from the South Bohemian Region (the rates of TBE cases imported from other Regions were less than 5%). And conversely, the residents of the South Bohemian Region (CZ031), with the highest number of TBE cases ever in the Czech Republic, acquired TBE in the region of domicile at a rate of 99.5%. These rates are clearly associated with the recreational potential of various Regions. The probable area of TBE acquisition is identified by cadastral community. In the light of the natural focality of TBE, the analysis of the local environmental factors involved in the circulation of TBE virus in the wild environment is required to determine the high-risk areas and local risk level. Although outbreaks of TBE cases in humans are indicative of TBE natural foci, more data is needed to delineate such areas. And similarly, the absence of TBE cases in humans over a period of time may not be indicative of a no risk area. PMID- 22324244 TI - The occurrence of microsporidial infections and toxoplasmosis in Slovak women. AB - AIM OF THE STUDY: To determine the prevalence of antibodies to intracellular pathogens (Toxoplasma gondii, Encephalitozoon cuniculi, and Encephalitozoon intestinalis) in sera of Slovak women. MATERIAL AND METHODS: Enzyme-linked immunosorbent assay (ELISA) was used for the detection of specific IgG antibodies to Toxoplasma gondii, Encephalitozoon cuniculi, and Encephalitozoon intestinalis in 118 sera samples from Slovak women with different diagnoses. RESULTS: Women were divided into three groups based on the age. In group 1 (n = 26, age > 51), nine women tested positive for T. gondii, two for E. cuniculi, and one for E. intestinalis. The respective numbers in group 2 (n = 53, age range 36-50) were 18, three, and seven, and in group 3 (n = 39, age range 20-35) 13, two, and four. In an attempt to find the relationship between the clinical diagnosis and the prevalence of the three pathogens, we divided the study subjects into four groups based on the condition (diseases of the nervous, respiratory, and immune systems and pregnancy). A statistically significant relationship between the diagnosis and the prevalence of a pathogen was found (p < 0.001). In women with diseases of the respiratory system, antibodies against Toxoplasma gondii were most often detected, while infection with E. intestinalis was most commonly associated with nervous system diseases and the highest seroprevalence of E. cuniculi was found in women diagnosed with immune system disorders. CONCLUSIONS: In our study, the seroprevalence rates of the three infections in pregnant women were similar, showing no significant difference. Women with diseases of the respiratory system were most often seropositive for T. gondii. Our result is consistent with the known fact that in humans, toxoplasmosis may affect various organs of the body, causing diverse clinical signs. However, the respiratory system is commonly involved and pneumonia may result. The most common finding is a mild, flu-like illness that lasts a few days. The women with different types of immunodeficiency disorders had the highest seropositivity rates for E. cuniculi and the second most common infection in this group was toxoplasmosis. Both of these parasites are opportunistic and can cause serious problems in immunocompromised individuals (HIV-positives, organ transplant recipients, chemotherapy patients). The women diagnosed with the nervous system disorders were most commonly infected with E. intestinalis. The relationship between the disease and this pathogen is not clear, but E. intestinalis is responsible for various pathologies; it causes mainly disseminated infections and damage to the digestive tract. E. intestinalis is a parasite very close to E. cuniculi affecting either the nervous system or the respiratory tract depending on the type of host. PMID- 22324245 TI - [Cases of menstrual toxic shock syndrome in the Czech Republic in 1997-2011]. AB - AIM: To determine toxigenicity and other basic characteristics of 47 strains of Staphylococcus aureus referred to the National Reference Laboratory for Staphylococci (NRL) as suspected causative agents of menstrual toxic shock syndrome (MTSS). MATERIAL AND METHODS: S. aureus strains were collected from 11 administrative regions of the Czech Republic in 1997-2011. The diagnosis was based on phenotypic (reverse latex agglutination test) and genotypic (polymerase chain reaction) methods. RESULTS: Forty-four S. aureus strains were producers of toxic shock syndrome toxin 1 (TSST-1), either alone or in combination with staphylococcal enterotoxin. Three strains only produced enterotoxin (B, C, and H). CONCLUSION: MTSS is a serious multisystem disease. In this study, MTSS often had a severe course requiring intensive care. All MTSS patients used vaginal tampons that had been identified in the literature as a risk factor for MTSS. The case of MTSS in a 36-year-old woman caused by an enterotoxin H positive strain of S. aureus is probably the first to be reported in the world. PMID- 22324246 TI - Isolation of Cronobacter spp. (formerly Enterobacter sakazakii) from nostrils of healthy stable horse--short communication. AB - Cronobacter spp. belongs to the family Enterobacteriaceae. It is a motile (peritricha) Gram-negative non-spore forming bacterium. At present, Enterobacter sakazakii is reported as a Cronobacter spp. species with 16 biogroups. It is a ubiquitous organism whose isolation used to be associated with a contaminated powdered infant formula and feed for neonates and infants. Information about the Cronobacter spp. species incidence in the environment, its potential dissemination and its vectors, is very limited. The authors have documented incidence of Cronobacter spp. in the nostril mucous membrane of a healthy stabled horse. The above points out at the absolutely insufficient and unsystematic information about the dissemination of the Cronobacter spp. strain in the environment of animals and the people who are in contact with them. PMID- 22324247 TI - [Secondary peritonitis prognosis assessment]. AB - INTRODUCTION: Secondary peritonitis is a severe disease with high mortality and morbidity. In the last 20 years the results of treatment of this disease have improved markedly. AIM OF THE STUDY: To determine statistically significant risk factors for mortality in patients with severe secondary peritonitis. MATERIAL AND METHODS: We studied in retrospective analysis the cohort of patients treated at our clinic in the period 2005-2010. 65 patients (38 men and 27 women) with an average age of 60.7 years were included. 27 patients died (41.5%). The average age of the died patients was 72 years. The average value of APACHE II was 20.77, which corresponds to the prediction of lethality 41.8%. The average value of the SOFA score was 11.87. RESULTS: The performed statistical analysis showed age over 65 years, bronchopneumonia, obesity, ischemic heart disease, artificial ventilation over 6 days and circulatory support over 10 days as statistically significant independent factors for mortality. Patients older than 65 years had 8.9 times greater risk of death. In the case of bronchopneumonia was the risk 4.8 times higher. Obesity increased the risk of death 3.1 times and ischemic heart disease 2.4 times. In the case of mechanical ventilation for more than 6 days and circulatory support for more than 10 days, these increased the risk of death 4.1 times respectively 4.3 times. DISCUSSION: The benefit for determining the prognosis secondary peritonitis is the use of scoring systems. It was also shown that the basic clinical data may have the same benefit for predicting the prognosis of patients as a sophisticated scoring systems. CONCLUSION: The performed retrospective analysis age over 65 years, bronchopneumonia, obesity, artificial ventilation and circulatory support as statistically significant independent factors for prediction of poor survival. These basic clinical factors correlated with scoring systems APACHE II a SOFA. PMID- 22324248 TI - [Late surgical conversion after endovascular treatment of the abdominal aortic aneurysm]. AB - The authors present a case report of long- term follow up of 66-year old male with the abdominal aortic aneurysm treated with aortouniiliac stent-graft implantation in combination with the cross-over femoro-femoral bypass 14 years ago. Various leaks type Ia, IIb and III developed during follow-up. In spite of endovascular treatment of these complications the size of the aneurysmal sac enlarged and the patient was successfully treated by the aortobifemoral bypass. PMID- 22324249 TI - [Rupture of the common illiac artery isolated aneurysm in a high risk patient--a case review]. AB - Rupture of isolated aneurysm of common iliac artery is a relative seldom finding in vascular surgery. Nowadays are in therapy of this severe conditions used conventional as well as endovascular procedures. Our case report document, that in high risk patients with convenient anatomical conditions endovascular therapy is a safe and effective therapy, that can reduce mortality of these patients. PMID- 22324250 TI - [Gall bladder adenomyomatosis]. AB - Adenomyomatosis of the gallbladder (AMG) is not very common, however inherited and degenerative disease of the gallbladder with premalignant to malignant potential through metaplasia, occurring especially in a segmental form at higher age patients, although the fundal form occurs more often. It can be found in 2 8.7% of resected gallbladder after cholecystecomy. In some cases, but extremely rarely, it has been found also in extrahepatic bile ducts. Correct pre-operative diagnosis does not exceed 30%, as it is often considered as an acute or chronic inflammatory gallbladder disease, same as in our case report. Disease development from the clinical point of view is mostly asymptomatic, where again the cholecystectomy is recommended. PMID- 22324251 TI - [Clinical outcomes of surgical management of acromioclavicular dislocation with and without ligament suturing]. AB - INTRODUCTION: The aim of the study was to present a retrospective assessment of clinical outcomes of acromioclavicular (AC) dislocation surgery with and without suturing of the coracoclavicular ligament (CC). MATERIAL AND METHODS: Patients regardless of their age and gender were included in the study. All the subjects were operated by the same surgeon using the same surgical technique--traction cerclage. Every odd-numbered patient's procedure included ligament suturing and every even-numbered patient was operated without ligament suturing. The patients underwent clinical follow up at identical time intervals, had Pruban (elastic net bandage) fixation applied for one week and had the same rehabilitation regime for 6 weeks. The wires were extracted at 6-8 months. A total of 42 patients were included in the study. All the subjects were classified according to Tossy III, based on x-ray findings. The study group included 36 males and 6 females. The average age was 31.8 years (17-55). In 14 cases, preoperative stress x-rays of the upper extremity were performed. CC ligmanet suture was completed in 21 patients and 21 patients underwent procedures without CC suturing. The clinical outcome was assessed after wire extraction. RESULTS: Painful complications were recorded in 2 subjects and they reported the pain to be intermittent. The pain was classified as maximum grade 4, based on VAS (Visual analogue score). In one patient, the authors recorded pain sensation in the area of Kirschner's wires endings. In this particular patient, the wires were extracted 6 weeks after the procedure and following that, the patient was symptom-free. CONCLUSION: Based on the findings, the authors recorded no differences in the clinical outcomes of AC surgery with or without CC ligament suturing. PMID- 22324252 TI - [Leiomyosarcoma of the inferior vena cava (case report)]. AB - The occur of resecable retroperitoneal tumours invading into inferier vena cava is rare. The authors report in detail a case of fibrosarcoma of the inferior vena cava In article is presented case of 49-year-old female presented with echographic and computed tomographic evidence of solid formation below porta hepatis and ower head of pankreas, behinde duodenum, growed into inferior vena cava with trombus. Treatment of the abdominal and retroperitoneal tumours closely related to major blood vessels must be interdisciplinary, considering diagnostics, operability estimation and additional measures. The radical resection rate for involving important vesel may bee improved with vascular technique. PMID- 22324253 TI - [Acute appendicitis--overview of current knowledge]. AB - Review of literature about acute appendicitis, the most common inflamatory abdominal emergency, is presented. Current knowledge on pathogenesis, clinical features, investigation and general management are discussed. A benefit of antimicrobial prophylaxis and use of diagnostic laparoscopy in childbearing age women are stressed. PMID- 22324254 TI - [A rare case of a long-term patent axillobipopliteal bypass--a case report]. AB - INTRODUCTION: One of the options for the treatment of vascular graft infection in the aortoiliofemoral region is its explantation and extra-anatomical reconstruction. The authors present a rare case of a long-term patent axillobipopliteal bypass. CASE REPORT: A polymorbid patient with complete infection of the aortobifemoral prosthetic graft, with abscess in the groin and bilateral occlusion of the superficial femoral artery was treated by complete graft explantation and implantation of extra-anatomical axillobipopliteal bypass. The occlusion of the distal part of the left limb of the graft after 6 years was successfully solved by reoperation replacement with a new vascular prosthesis. DISCUSSION: The advantage of the extra-anatomical axillo(bi)femoral/popliteal reconstruction is its usability in urgent conditions. However, this reconstruction is associated with a high risk of graft thrombosis because of the length of the graft. Currently, we prefer an autogenous femoral vein for the treatment of the graft infection in the aortoiliofemoral region. CONCLUSION: Although the long-term results of the axillo(bi)femoral/popliteal reconstructions are generally not favourable, the secondary patency of the extra-anatomical bypass in presented patient is maintained for more than 6 years. PMID- 22324255 TI - [Comparison of micturition, sexual and defecation disorders in females following type B and C pelvic fractures]. AB - INTRODUCTION: The objective of this work is to present results obtained in a three-year study focussed on micturition, defecation and sexual disorders in women of active age. METHODS: The monitored set consisted of 33 female patients treated in 2004-2009 for unstable pelvic fracture (B-type or C-type according to AO classification). Out of them 25 patients suffered B-type fracture and 8 patients suffered C-type fracture. Their age ranged between 17 and 55 years (the average age was 32 years). Anamnestic data were obtained based on UIQ, UDI and PISQ12 questionnaires. The non-parametric Mann-Whitney U-test was used for answers to individual questions representing nominal/ordinal variables. After finding a statistically significant difference in answers between both groups of patients, it was investigated by means of Pearson Chi2-test which answers are behind this statistically significant difference. If the number of answers to any question was less than 5, the exact Fisher test was used. In the event the rate equalled 0, Haldane correction was applied. All tests were considered statistically significant if the significance level was below 5%. RESULTS: The occurrence of urologic problems was higher in the B-type fracture patients (84% vs. 50%), however, afflictions were more severe in the C-type fracture patients. Intestinal problems were more frequent in the C-type fracture patients (75% vs. 52%) and they were also more severe. Also sexual problems were more frequent in the C-type fracture patients (75% vs. 40%), although according to individual answers it was not possible to state that their sexual life was unequivocally worse. CONCLUSION: The analysis of comparison of micturition, sexual and defecation problems in patients one year after the unstable pelvic fracture showed in some respects higher problems in the patients who had suffered the C type fracture. However, more important are the following observations, generally related to unstable pelvic fracture patients: 1. The occurrence of micturition, sexual and defecation problems was unexpectedly high; 2. Without active examination by a traumatologist during the after-treatment "minor" problems may escape his/her attention and may negatively affect life of each individual patient in the longer run; 3. A targeted method of detection of problems by means of questionnaires could lead to their disclosure; 4. A urologist, urogynaecologist, sexologist and proctologist have an indisputable place in the treatment of women who suffered a severe pelvic trauma. PMID- 22324256 TI - [Surgical management of jejunal diverticulosis complications]. AB - Jejunal diverticulosis is a rare disorder and the course of the disease is mostly asymptomatic. A surgeon meets the patients only in the acute phase of the disease, when the disease symptoms most commonly include bleeding and perforation. Jejunum is difficult to examine using the common visaulization methods and endoscopic methods, therefore, the diagnostics of the disease is difficult and the disease may often mask other disorders. The authors present two case reviews of patients operated for perforation and bleeding from jejunal diverticles. PMID- 22324257 TI - [Relapsing urinary tract infections as a single symptom of a foreign body within the GIT in a diverticulosis patient]. AB - Recidiving urinary tract infections and pneumaturia are the cardinal symptoms of colovesical fistula. The authors present a case of rare complication of diverticulosis and gastrointestinal foreign body, that only had urological symptomatology. PMID- 22324258 TI - [Large intestine bleeding caused by the lienal artery pseudoaneurysm rupture complicating a pancreatic pseudocyst]. AB - Bleeding pseudoaneurysm of a peripancreatic artery is a rare cause of gastrointestinal haemorrhage. Arterial pseudoaneurysm develops as a result of partial enzymatic damage of arterial wall in acute or chronic pancreatitis. The authors report the case of a 60-years old man with bleeding into the lienal flexure of the colon due to the erosion of the pseudoaneurysm of a branch of splenic artery into the pancreatic pseudocyst in the tail region of the pancreas communicating with the colon. The diagnosis was established by CT-scan and angiography. The patient underwent surgery with the ligation of the bleeding vessel and the resection of the part of the colon. PMID- 22324259 TI - [Traumatic atlantoaxial rotatory fixation in a child]. AB - Traumatic atlantoaxial rotary fixation is defined as low-energy mechanism injury resulting in fixed subluxation of the atlantoxial complex expressing oneself as a slight head flexion, lateral tilt of the head to one side, head rotation to the other side and painful limitation of motion that makes it impossible to turn head to the contralateral side voluntary. As a result of the rarity of the injury it is often neglected, treated improperly, treated for the duration, or it has permanent consequences. We present a case report of a 10 year old patient treated in our department with acute traumatic atlantoaxial rotary fixation. The diagnosis was made on the basis of synthesis of anamnestic data, clinical picture and static CT examination. The patient was successfully treated conservatively. In the discussion we present a brief look at the etiopathogenesis, diagnosis and treatment of the injury. Its pathogenesis is still not fully understood. The most reliable diagnostic methods are dynamic X-ray and dynamic CT examinations. In our discussion, more is dedicated to clinical diagnostics, and static X-ray and CT examinations as a way likely to lead together with anamnestic data on the accident at the correct diagnosis even in the absence of acute dynamic CT or X ray examinations. The treatment of acute traumatic atlantoaxial rotary fixation is usually indicated for conservative treatment, with excellent results. Neglected cases generally require surgical intervention. Treatment of neglected atlantoaxial rotary fixation is usually difficult and permanently distorting anatomical growing organism. PMID- 22324260 TI - Predicting adverse outcomes following trauma in pregnancy. AB - OBJECTIVE: To identify variables predicting adverse maternal or fetal outcome following trauma and to establish a composite morbidity model to predict poor obstetrical outcomes. STUDY DESIGN: A retrospective study of pregnant women following major and minor trauma from a single institution from 1985-2007 was performed. Abstracted data included maternal demographics, Injury Severity Score (ISS), laboratory and radiology studies,fetal monitoring and delivery information. Linear algorithm and logistic regression analysis estimated predictors of adverse obstetrical outcomes. Accuracy of composite morbidity models was tested using receiver operating characteristic. RESULTS: A total of 292 pregnant trauma patients were analyzed. Forty-eight (13%) women had an ISS > or = 10. Adverse pregnancy outcomes occurred in 71 patients (24%). Predictors of poor outcomes included trauma in the third trimester, length of stay (LOS) >2 days, abdominal trauma, ISS >2 and a positive Kleihauer-Betke (KB) test. Composite morbidity models resulted in sensitivity and specificity ranging from 54.3% to 70.4% and 59.5% to 87.5%, respectively. CONCLUSION: Predicting adverse perinatal outcomes following major trauma remains challenging. Composite morbidity models using a combination of third trimester trauma, LOS > 2 days, abdominal trauma, ISS >2 or a positive KB test improves identification of those at risk for adverse perinatal outcomes. PMID- 22324261 TI - Elevated progesterone-to-estradiol ratio versus serum progesterone alone for predicting poor cycle outcome with in vitro fertilization. AB - OBJECTIVE: To determine whether a progesterone-to-estradiol (P/E2) ratio on day of human chorionic gonadotropin (hCG) administration would be a better predictor of in vitro fertilization (IVF) outcome than serum P alone. STUDY DESIGN: All 348 fresh IVF cycles performed in 2002 and 2003 at a university hospital center were reviewed for all cycle parameters as related to the peak P and peak P/E2 ration on day hCG administration. RESULTS: Out of the 348 cycles performed, 199 cycles resulted in clinical pregnancies. The mean P level (1.4 ng/mL) was equivalent in both conception and nonconception cycles. A P/E2 ratio > 1.0, however, was associated with a highly significant reduction in clinical pregnancy rate (38.2% vs. 62.6%, p< 0.01) and live birth rate (35.4% vs. 49.1%, p = 0.02). CONCLUSION: Cycles with elevated P/E2 ratios are associated with lower clinical pregnancy and live birth rates, which decrease further as the P/E2 ratio rises. P/E2 ratio improves the prediction of IVF outcome when compared to serum P levels alone. PMID- 22324262 TI - Hysteroscopic metroplasty in women with primary infertility and septate uterus: reproductive performance after surgery. AB - OBJECTIVE: To assess reproductive performance in women with septate uterus and otherwise unexplained infertility after hysteroscopic metroplasty. STUDY DESIGN: A total of 72 women with septate uterus and otherwise unexplained primary infertility were included in the study. All of the women underwent hysteroscopic septal resection. Reproductive performance of these women within one year of surgery was studied and analyzed. RESULTS: Thirty-three women (45.83%) conceived within one year of surgery. Only 4 women (12%) had spontaneous abortions, and only 5 (15%) had preterm delivery. CONCLUSION: Hysteroscopic metroplasty in women with septate uterus significantly improves reproductive outcomes. PMID- 22324263 TI - Women presenting to an emergency facility with abnormal uterine bleeding: patient characteristics and prevalence of anemia. AB - OBJECTIVE: To describe the population of women seeking urgent medical attention for abnormal uterine bleeding (AUB), in terms of symptoms, medical history and clinical examination findings, and to determine characteristics associated with anemia in this population. STUDY DESIGN: We performed a retrospective cohort study of patients seen in the Women and Infants Hospital Emergency Room for AUB from August 2005 to February 2006 (n = 378). Data collected included demographic factors, clinical history, physical examination findings, and laboratory and radiologic findings. We calculated prevalence ratios for moderate to severe anemia (defined as hemoglobin <10 g/dL) and sensitivity and specificity of clinical characteristics for identifying women with anemia. RESULTS: The median age of patients was 32 years (range, 12-72 years). Approximately half (49.2%) had a concurrent medical condition which could affect their treatment options, and 14% had moderate to severe anemia. The only factors associated with moderate to severe anemia were (1) having both tachycardia and hypotension, (2) duration of bleeding >7 days and (3) hemoglobin of <10 g/dL in the previous year. CONCLUSION: A substantial proportion of patients seeking urgent medical attention for AUB had potential contraindications for the mainstays of treatment. Clinical symptoms and bleeding history were poorly predictive for moderate to severe anemia in this population of women. PMID- 22324264 TI - Lobular lesions of the breast: imaging findings of lobular neoplasia and invasive lobular carcinoma. AB - The clinical and radiological diagnoses of lobular neoplasia (LN) and invasive lobular carcinoma (ILC) are difficult because they have no specific findings. The purpose of this study is to illustrate the imaging and pathological features of LN and ILC. For lobular lesions, imaging is the basic and essential diagnostic tool, so the understanding and effective use of multimodality imaging findings are important. This article shows imaging findings of LN, which are seldom known, and ILC as well as their characteristic histopathological features. PMID- 22324265 TI - Risk factors for late postpartum preeclampsia. AB - OBJECTIVE: To determine the risk factors for late postpartum preeclampsia. STUDY DESIGN: This was a retrospective case control study of women readmitted in the postpartum period (>48 hours and <4 weeks) with preeclampsia. Inclusion criteria were readmission with confirmed preeclampsia. Variables examined were age, race, parity, gestational hypertension, preeclampsia in labor, mode of delivery and history of preeclampsia in previous pregnancies. RESULTS: Data included 51 women who met the criteria for late postpartum preeclampsia. Initial analysis revealed that antenatal preeclampsia, gestational hypertension, preeclampsia in a prior pregnancy, body mass index (BMI) > 30, African American race and cesarean delivery were all predictive of late postpartum preeclampsia. Asian ethnicity was protective. Final analysis using logistic regression concluded that African American race, cesarean delivery, BMI and hypertensive disease during the incident pregnancy were all significant predicators of late postpartum disease. CONCLUSION: BMI >30, antenatal hypertensive disease, cesarean delivery and African American race were all predictive of readmission for late postpartum preeclampsia. Asian ethnicity appeared to be protective against developing late postpartum preeclampsia. PMID- 22324266 TI - Evaluation of B-type natriuretic peptide levels in singleton hypertensive minority women. AB - OBJECTIVE: To determine the pattern of the B-type natriuretic peptide (BNP) levels in minority women presenting with elevated blood pressure during pregnancy. STUDY DESIGN: A review of 503 charts was undertaken, in sequence, of pregnant women who presented to the service with elevated blood pressure or had been referred there for suspected hypertension. Serum BNP levels had been obtained and other diagnostic procedures performed. Ultimately 283 women were determined not to meet the criteria for hypertension or were normotensive. A total of 110 patients met the criteria for gestational hypertension, and 68 patients met the criteria for preeclampsia. RESULTS: There were no differences in BNP levels among women of Hispanic and of African heritage in each category. BNP levels were significantly higher in women in the preeclamptic group, whether of African or Hispanic heritage. The negative predictive values for women with preeclampsia were 87.04% for women of African heritage and 96.38% for women of Hispanic origin. CONCLUSION: No differences in BNP levels were found among minority women of African or Hispanic descent. Serum BNP levels provide useful information for the clinical evaluation and management of singleton patients presenting to triage hypertensive after 20 weeks of pregnancy. PMID- 22324267 TI - Clinical audits: A practical strategy for reducing cesarean section rates in a general hospital in Tehran, Iran. AB - OBJECTIVE: To investigate whether the introduction of clinical audits by the Safe Motherhood Committee of a general hospital in Tehran, Iran, influenced cesarean section (CS) rates, STUDY DESIGN: A retrospective study was performed. The number of deliveries before and after the institution of clinical audits (May to December 2005) were tabulated in the audited hospital and analyzed by Chi(2) test. Additionally, CS rates were measured in 3 other general hospitals during the same time period for comparison. RESULTS: A total of 3,494 deliveries were recorded during the study periods in 2004 and 2005 at the audited hospital. Subsequent to the audit, the overall CS rate decreased from 40% to 33% (p < 0.001) and the primary CS rate from 29% to 21% (p < 0.001), accounting for a 27% reduction in the risk of primary CS. In 2006 CS rates reverted to 42%. None of the other 3 general hospitals indicated a decline in CS rates in 2005. CONCLUSION: Our findings show a preventive association between the clinical audits and CS rates in a general hospital. The implementation of a clinical audit process can be an effective way to track care pathways and reduce unnecessary CS deliveries. PMID- 22324268 TI - Serum ischemia modified albumin levels in pregnancies with neural tube defects. AB - OBJECTIVE: To evaluate ischemia-modified albumin (IMA) in women who had been pregnant with a child suffering from neural tube defect. STUDY DESIGN: Samples from 50 women who had been pregnant with an affected child (25 spina bifida, 25 anencephaly) and 25 controls matched for age, gestational age, and body mass index were studied. We measured serum IMA by enzyme-linked immunosorbent assay. RESULTS: Serum IMA was significantly higher in the study group compared to normal pregnancies (p < 0.05). The area under the receiver operating curve was 0.858 for IMA (95% CI, 0.769-0.947), whereas the optimal threshold value of IMA to discriminate between affected children and controls was 0.409 (sensitivity 88%, specificity 80%). The risk for increased IMA in mothers who have conceived a fetus with neural tube defect is 24.5 times higher than in the control group (rr = 24.5, 6.9-86.9, 95% CI) (p = 0.001). CONCLUSION: This study indicates that serum IMA in women who have conceived a fetus with neural tube defect is significantly higher than that in normal pregnant women. PMID- 22324269 TI - Grandmultiparity: a potential risk factor for adverse pregnancy outcomes. AB - OBJECTIVE: To assess the incidence of antenatal and intrapartum and perinatal outcomes in grandmultiparae in an affluent society with available modern perinatal care. STUDY DESIGN: A case-control study in a tertiary referral hospital in Eastern Saudi Arabia of 2,122 grandmultiparae was undertaken. Each patient was compared with an age-matched multipara who delivered during the 10 year study period. Data was obtained from the computerized hospital information systems and their statistical analysis performed to determine the significant categorical variables. RESULTS: Grandmultiparity was associated with a significantly higher risk of iron deficiency anemia, diabetes mellitus, antepartum hemorrhage, malpresentation, cesarean section rate, postpartum hemorrhage and a high perinatal mortality rate. There was no significant difference in chronic hypertension in pregnancy, preterm labor, congenital fetal malformations, obstructed labor and cord prolapse between the two groups of patients. CONCLUSION: Grandmultiparae are a high-risk obstetric group of patients liable to develop a number of antepartum and intrapartum complications with adverse neonatal outcome. The best prophylaxis of these high risks in pregnancy would be the prevention of grand multiparity. Women need to be informed of the dangers of high-order births and advised to practice effective family planning methods to prevent pregnancy. PMID- 22324270 TI - Cesarean hysterectomy requiring emergent thoracotomy: a case report of a complication of placenta percreta requiring a multidisciplinary effort. AB - BACKGROUND: Currently a leading indication for cesarean hysterectomy among multiparous women, placenta accreta is associated with significant maternal morbidity and mortality. CASE: A 34-year-old woman with a pregnancy complicated by placenta previa and previous cesarean deliveries was transferred to our institution following late diagnosis of placenta percreta. She underwent cesarean hysterectomy complicated by substantial hemorrhage. Massive blood product replacement precipitated severe hyperkaIemia and hypocalcemia with resultant asystole. Cardiac bypass with concomitant obligate anticoagulation was temporarily required while normalizing the patient's electrolytes. Numerous surgical and medical interventions were required to achieve hemostasis, and the patient survived to hospital discharge with moderate residual morbidity. CONCLUSION: Optimal management of placenta accreta requires a multidisciplinary approach within a tertiary center possessing extensive resources necessary for managing the most severe complications. PMID- 22324271 TI - Late-first-trimester cesarean section scar ectopic pregnancy with placenta increta: a case report. AB - BACKGROUND: Cesarean section scar pregnancy is a rare ectopic pregnancy that is difficult to manage due to high risk of uterine rupture and maternal hemorrhage-a risk that increases with gestational age. CASE: A 21-year-old, gravida 3 para 2 woman was diagnosed at 13.5 weeks' gestation by pelvic ultrasound and magnetic resonance imaging with a cesarean scar ectopic pregnancy and placenta increta. Surgical removal of the pregnancy via exploratory laparatomy with intraoperative use of vasopressin minimized initial blood loss. However, extraction of the placenta increta resulted in uncontrolled bleeding, requiring a supracervical hysterectomy. CONCLUSION: This is the first case report, to our knowledge, of a late-first-trimester cesarean section scar ectopic pregnancy with placenta increta. Early identification of the ectopic pregnancy may allow for more conservative, nonsurgical management. However, with a more advanced gestational age and placenta increta, surgical management is most appropriate to minimize associated maternal risks. A transverse wedge resection of the implantation site, uterine artery embolization, uterine artery ligation, endovascular balloon catheters, or uterine artery tourniquet may help decrease bleeding during surgical extraction of the pregnancy and placenta increta, and also may prevent a hysterectomy. PMID- 22324272 TI - Giant paraovarian cysts in young adolescents: a report of three cases. AB - BACKGROUND: Very large pelvic cysts in young adolescents present a challenge in diagnosis and management. When such cysts present shortly after menarche, measure > 20 cm and appear simple on ultrasound or MRI, the diagnosis is likely a benign paraovarian cyst. CASES: Three young adolescents within 2 years of menarche presented with abdominal distention and masses. On ultrasound and MRI each was confirmed to be a large simple cyst ranging from 20-26 cm in diameter. In each case the simple cyst was drained through a very small incision, allowing the decompressed cyst and adnexa to be externalized and a cystectomy to be performed. The final pathology in each case was consistent with a paraovarian cyst. CONCLUSION: The peak incidence of paraovarian cysts is in the fourth and fifth decades of life; however, larger paraovarian cysts are more common in postpubertal teenagers. This is likely due to the fact that smaller asymptomatic cysts go unrecognized until later in life when they are found incidentally. Ultrasound is helpful in making the diagnosis in a young patient. Such cysts are unlikely to be malignant, and the least invasive approach possible in a young patient is preferable. PMID- 22324273 TI - Primary intestinal-type adenoma of the vagina arising directly from endocervical type adenosis: a case report. AB - BACKGROUND: Tubular or villous adenomas are common neoplasms of the gastrointestinal tract. Other locations where these adenomas are found, including the female genital tract, are very rare. A literature review documents that only eight cases of tubular or villous adenomas found within the vagina have been published. CASE: A 25-year-old, Caucasian woman presented with a history of primary infertility and postcoital bleeding. Gynecologic examination revealed a polypoid mass attached to the lateral wall of the vagina, approximately 2 cm above the introitus. The polypectomy specimen was a soft, tan, polypoid mass measuring 2 x 1 x 0.8 cm in size. Microscopically, the lesion was identical to pure tubular adenomas of the large intestine. Positive immunohistochemical staining for cytokeratin (CK) 20, CK 7, CEA and Cdx2 were identified. CONCLUSION: An intestinal-type adenoma should be included in the differential diagnosis of a vaginal polypoid mass lesion in women. Our review of the literature presents the risk of malignant transformation. PMID- 22324274 TI - Spontaneous vulvar hematoma during pregnancy: a case report. AB - BACKGROUND: Vulvar hematoma is a relatively uncommon occurrence. Most have been described resulting from traumatic injury in nonpregnant women or as an uncommon complication of childbirth. We describe a case of a spontaneous 6-cm vulvar hematoma that presented as unexplained vulvar edema in a 35-weeks-pregnant woman. CASE: A pregnant woman presented to the obstetrics triage unit with rapid onset unilateral vulvar swelling and no preceding traumatic event. A detailed physical examination and radiologic evaluation revealed a spontaneous vulvar hematoma as the cause. After incision and drainage of the hematoma, her edema resolved and the patient went on to have an uneventful vaginal delivery 4 weeks later. CONCLUSION: Spontaneous vulvar hematoma is a rare event. Rapid recognition and treatment in this case allowed for complete recovery and enabled this pregnant woman to continue a normal pregnancy with uncomplicated spontaneous vaginal delivery. PMID- 22324275 TI - Significance of pelvic magnetic resonance imaging in preoperative diagnosis of incarcerated retroverted gravid uterus with a large anterior leiomyoma: a case report. AB - BACKGROUND: Incarceration of the gravid uterus is a rare but serious complication of pregnancy. The often required cesarean section is technically complicated, and preoperative planning is critical. An important initial surgical step is to lift the fundus out of the pelvis prior to creating the hysterotomy in order to facilitate adequate visualization of the pelvic anatomy. CASE: A 38-year-old primigravida with uterine incarceration from a large anterior leiomyoma underwent cesarean delivery at 29 weeks' gestation. In this case, a failure of the fundal height to increase was not appreciated as the anterior leiomyoma was palpated to represent the fundus. Intraoperatively the uterus was unable to be repositioned because of the leiomyoma. However, the surgery did proceed smoothly primarily due to the highly detailed images obtained on pelvic magnetic resonance imaging. CONCLUSION: Although uterine incarceration is rare, knowledge of this condition is important. Magnetic resonance imaging is a useful tool in that it enables the detailed evaluation of the pelvic anatomy in cases with suspected uterine incarceration. PMID- 22324276 TI - Can ovariopexy at the end of surgery for endometriosis be recommended? A case report. AB - BACKGROUND: Endometriosis affects 10-15% of the female population in the reproductive period and is detected in up to 40% of infertile women. Surgery is indicated to improve fertility and symptoms in these women, but some patients experience severe complications and develop postoperative adhesion. We discuss the potential impact on adhesion of systematic ovariopexy at the end of surgery for endometriosis. CASE: We report a case of a 31-year-old woman who underwent initial laparoscopic removal of endometriomas and rectovaginal endometriosis with bilateral transient ovariopexy five years ago. She was referred for recurrence of symptoms and infertility. Preoperative transvaginal sonography and MRI confirmed the recurrence of endometriosis with bilateral uterosacral ligament and rectal involvement. At laparoscopy severe and dense adhesions of the ovaries to the anterior abdominal wall using nonabsorbable suture were observed associated with distortion of tubal anatomy. In addition to the removal of these adhesions, a sigmoid adhesiolysis was performed with uterosacral ligament, rectosigmoid and vaginal resections, followed by a systematic protective colostomy. CONCLUSION: This case illustrates the deleterious impact on adhesions to the abdominal wall of transient ovariopexy at the end of surgery for endometriosis. PMID- 22324277 TI - Successful pregnancy after treatment of a cervical gestational trophoblastic neoplasia: a case report. AB - BACKGROUND: Primary gestational trophoblastic neoplasia of the uterine cervix is exceptionally rare, with fewer than 100 cases reported worldwide. CASE: A 33-year old, gravida 1, para 1, Filipino woman was admitted due to vaginal bleeding nearly 7 months after delivery of a full-term, stillborn infant. Transvaginal ultrasound revealed a heterogeneous, predominantly solid, vascular mass at the upper half of the cervix measuring 3.05 x 3.75 x 3.6 cm. Serum beta human chorionic gonadotropin (beta-hCG) on admission was 101,922.5 mIU/mL. She was initially treated with single-agent chemotherapy in the form of methotrexate. Rising levels of serum beta-hCG after the third cycle necessitated a shift to multiagent chemotherapy in the form of etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine. The patient achieved remission after 6 cycles and eventually achieved a successful pregnancy. CONCLUSION: Primary gestational trophoblastic neoplasia of the cervix can be treated successfully using chemotherapy. PMID- 22324278 TI - Endoscopic balloon dilation in the management of ureteral stricture after urogynecologic surgery: a case report. AB - BACKGROUND: Ureteral injuries are known complications of urogynecologic surgery. Until now, ureteral reimplantation with laparotomy has been used in cases in which ureteral stenting of distal obstruction was unsuccessful. CASE: We report a case of a 74-year-old woman with a recognized right ureteral injury after vaginal reconstructive surgery that failed ureteral stenting to relieve the obstruction and who presented with ureteral stricture and mild hydronephrosis 6 weeks postoperatively. Ureteroscopy with endoscopic balloon dilation reduced the stricture successfully. The patient remains asymptomatic, with normal renal sonogram, 6 months after the procedure. CONCLUSION: Endoscopic balloon dilation is an effective technique that can be used for the management of ureteral strictures after urogynecologic surgery and avoids further surgical intervention. PMID- 22324279 TI - Perceptual comparisons with laterally presented pictures and environmental sounds. AB - Two experiments studied perceptual comparisons with cues that vary in one of four ways (picture, sound, spoken word, or printed word) and with targets that are either pictures or environmental sounds. The basic question probed whether modality or differences in format were factors that would influence picture and sound perception. Also of interest were cue effect differences when targets are presented on either the right or left side. Students responded to a same different reaction time task that entailed matching cue-target pairs to determine whether the successive stimulus events represented features drawn from the same basic item. Cue type influenced reaction times to pictures and environmental sounds, but the effects were qualified by response type and with picture targets by presentation side. These results provide some additional evidence of processing asymmetry when pictures are directed to either the right or left hemisphere, as well as for some asymmetries in cross-modality cuing. Implications of these findings for theories of multisensory processing and models of object recognition are discussed. PMID- 22324280 TI - A Simon effect for depth in three-dimensional displays. AB - We investigated whether the Simon effect occurs for the depth dimension in a 3 dimensional display. In Experiment 1, participants executed discriminative responses to 2 stimuli, a cross and a sphere, both 3-dimensional, which were perceived to be located near or far with respect to the participant's body. The response keys were located near and far along the participant's midline. Apparent stimulus spatial location (near or far) was irrelevant to the task. Results showed a depth Simon effect, attributable to the apparent stimulus spatial location. Experiment 2 replicated Experiment 1 with a different procedure. The 2 stimuli, a triangle and a rectangle, were 2-dimensional and were perceived as being located near or far from the participant's midline; the response keys were located near and far along the participant's midline. Results showed again the depth Simon effect. Experiment 3 was a control condition in which the 2 stimuli, drawings of a lamp and of a chair, had the same size, regardless of whether they appeared to be near or far. The depth Simon effect was replicated. A distribution analysis on data of Experiment 3 showed that the Simon effect increased as reaction times became longer. In Experiment 4, the position of the 2 stimuli, a circle and a cross, varied on the horizontal (right or left) dimension, whereas the position of the 2 responses varied along the depth (near or far) dimension. No Simon effect was found. PMID- 22324281 TI - Classic Stroop Negative Priming effects for children and adults diverge with less conflicting and nonconflicting conditions. AB - Negative priming indexes an inhibition process that aids target selection by reducing distractor interference. To date, children have produced negative priming only in tasks where distractor response tendencies are consistently greater than or equal to targets and not in tasks containing a substantial proportion of low-conflict distractors. To establish the exact parameters under which children's negative priming attenuates relative to adults, we varied processing demands across 2 experiments involving children and adults. Negative priming was comparable when 100% high-conflict conditions were encountered (Experiment 1) and was intact in adults but not children when a ratio of 50:50 high- to low-conflict conditions was encountered (Experiment 2). Compared with adults, children seem induced to divide attention more generally when low conflict attentional conditions are included, attenuating negative priming. PMID- 22324282 TI - Processes of conscious and unconscious memory: evidence from current research on dissociation of memories within a test. AB - The processes of conscious memory (CM) and unconscious memory (UM) are explored, based on the results of the current and previous studies in which the 2 forms of memory within a test were separated by either the process dissociation or metacognition-based dissociation procedure. The results assessing influences of shallow and deep processing, association, and self-generation on CM in explicit and implicit tests are taken as evidence that CM in a test is driven not only conceptually but also by the driving nature of the test, and CM benefits from an encoding condition to the extent that information processing for CM recapitulates that engaged in the encoding condition.Those influences on UM in explicit and implicit tests are taken to support the view that UM in a test is driven by the nature of the test itself, and UM benefits from an encoding condition to the extent that the cognitive environments at test and at study match to activate the same type of information (e.g., visual, lexical, or semantic) about memory items or the same content of a preexisting association or categorical structure. PMID- 22324283 TI - Workload and stress in vigilance: the impact of display format and task type. AB - Signal salience was manipulated using configural and object displays to examine their effects on the performance, workload, and stress of vigilance. Improving performance and reducing the workload and stress of vigilance are crucial concerns. Signal salience improves performance and reduces stress, but to date there have been no salience manipulations using configural displays in a vigilance task. Two task types (individual variable monitoring and midpoint identification) and 3 display formats (bar graph-different baselines, bar graph common baseline, and a polygon graph display) were examined. Configural displays improved performance in the midpoint identification task but not in the individual variable monitoring task. Workload depended on the form of display features (bar graph vs. polygon). Stress increased across all conditions, but task and display format did not affect stress. The midpoint identification task was associated with more emotion-focused and avoidant coping. Increasing signal salience in a vigilance task using configural displays with emergent features or physical contours can improve performance and reduce the decrement. These displays may not reduce the stress of vigilance or encourage task-focused coping. Therefore, there may be hidden costs to vigilance performance even when highly salient configural displays are used. PMID- 22324284 TI - Pygmalion in the laboratory. AB - Testers and bystanders can inadvertently lead subjects to answers in laboratories and in classrooms, in face-to-face tests of human beings and other animals. Many modern investigators avoid leading by using blind tests scrupulously. This article shows how to design blind tests and illustrates common methodological errors that allow leading to confound experimental results. The object is to help experimenters, editors, and readers detect and avoid a common experimental error that often has profound theoretical implications. PMID- 22324285 TI - Arithmetic in the chimpanzee Basso in the Frankfurt Zoological Park together with remarks to animal psychology and an open letter to Herr Krall from Karl Marbe. 1917. PMID- 22324286 TI - Properties and promises of nanosized insertion materials for Li-ion batteries. AB - The substantial influence of crystallite size on the properties of Li-ion storage materials has spurred intensive research in the emerging area of nanoionics. The development of nanoscale storage materials offers a promising strategy to increase the energy storage capabilities of Li-ion batteries, potentially making them suitable for electric vehicles. Nanosizing, which increases surface area, enhances the importance of interfaces and surfaces on directly observable materials properties such as the voltage profile and the phase diagram. As a result, nanosized materials can show improved storage properties, and materials inactive at the micro size can become excellent storage materials. We suggest novel surface storage mechanisms to explain these phenomena. First-order phase transitions, which are responsible for the batteries' constant voltage output, are partially suppressed at the nanoscale. So far the morphological changes during the phase transition remain unclear. A complete understanding of the equilibrium and non-equilibrium properties of a collection of nanosized electrode particles within an actual electrode remains a formidable challenge. In this Account, we describe the efforts toward understanding the effects of nanosizing and its applications in representative insertion materials. We are particularly interested in the mechanisms and properties that will help to increase the energy storage of Li-ion batteries. We review and discuss the nanosize properties of lithium insertion materials, olivine LiFePO4, and titanium oxides. Although nanosizing intrinsically destabilizes materials, which is potentially detrimental for battery performance, the relative stability of oxide and phosphate insertion compounds makes it possible to exploit the advantages of nanosizing in these materials. The larger capacities and typical voltage profiles in nanosized materials appear to be related to the surface and interface properties that become pronounced at the nanosize, providing a potential means of tailoring the material properties by particle size and shape. The large irreversible capacity at the surface of some materials such as titanium oxides represents a disadvantage of nanosizing, but research is suggesting ways to resolve this problem. The changes in the first-order phase transition upon (de)lithiation could be related to the interface between the coexisting phases. At these interfaces, concentration gradients and strain lead to energy penalties, which significantly influence the thermodynamics of nanomaterial grains. However, it is less clear what nanoscaling effects predominate in the large collection of particles in actual electrodes. The complexity of these materials at the nanoscale and the difficulty in observing them in situ pose additional challenges. Future demands for stored electricity will require significant research progress in both nanomaterials synthesis and in situ monitoring. PMID- 22324287 TI - Rough fibrils provide a toughening mechanism in biological fibers. AB - Spider silk is a fascinating natural composite material. Its combination of strength and toughness is unrivalled in nature, and as a result, it has gained considerable interest from the medical, physics, and materials communities. Most of this attention has focused on the one to tens of nanometer scale: predominantly the primary (peptide sequences) and secondary (beta sheets, helices, and amorphous domains) structure, with some insights into tertiary structure (the arrangement of these secondary structures) to describe the origins of the mechanical and biological performance. Starting with spider silk, and relating our findings to collagen fibrils, we describe toughening mechanisms at the hundreds of nanometer scale, namely, the fibril morphology and its consequences for mechanical behavior and the dissipation of energy. Under normal conditions, this morphology creates a nonslip fibril kinematics, restricting shearing between fibrils, yet allowing controlled local slipping under high shear stress, dissipating energy without bulk fracturing. This mechanism provides a relatively simple target for biomimicry and, thus, can potentially be used to increase fracture resistance in synthetic materials. PMID- 22324288 TI - The influence of treatment with pegylated interferon-alfa and ribavirin on neutrophil function and death in patients with HIV/HCV coinfection. AB - In patients with human immunodeficiency virus (HIV) as well as in patients with hepatitis C virus (HCV) infection the impairment of neutrophil activity is observed. We decided to analyze how treatment with pegylated interferon-alfa (Peg IFN-alfa) and ribavirin affects neutrophil function in HIV/HCV coinfected patients. The study group consisted of 18 patients with HIV/HCV coinfection, on combination antiretroviral treatment (cART), aged between 27 and 42 y (mean 33.1+/-4.5 y). At the beginning of treatment with Peg-IFN-alfa and ribavirin all patients had an undetectable HIV viral load, and CD4 T-cell counts higher than 350 cells/MUL. At two time points, before and after 12 wk of treatment with Peg IFN-alfa and ribavirin, we examined intracellular levels of reactive oxygen species (ROS), and expression of selected adhesion molecules on whole blood neutrophils, along with apoptosis and necrosis of these cells. These analyses were done with flow cytometry. During anti-HCV therapy undetectable HIV levels were maintained in all patients. Treatment with PEG-IFN-alfa and ribavirin resulted in increases in the expression of CD11b and CD18, and decreases of CD16 and CD62L. However, only the change in CD62L expression was statistically significant (p<0.05). Moreover, the treatment resulted in increased apoptosis of neutrophils, while necrosis remained unchanged. After 12 wk of treatment, an increase in ROS production by neutrophils stimulated with PMA was observed (p<0.01). In HIV/HCV coinfected patients on cART, PEG-IFN-alfa and ribavirin treatment caused an activation of neutrophil function, yet it did not affect the suppression of HIV replication. PMID- 22324289 TI - Time-of-day effects in arousal: disrupted diurnal cortisol profiles in children with ADHD. AB - BACKGROUND: Fluctuations in attention-deficit hyperactivity disorder (ADHD) symptoms related to regulatory deficits in arousal states are themselves characterized by circadian rhythms. Although cortisol is an important circadian arousal-related marker, studies focusing on across-the-day cortisol variations in ADHD are scarce. There is no study with multiple measurements to take into account interday and intraday variability. METHODS: Salivary cortisol was sampled five times a day (awakening, 30 min after awakening, noon, 4 p.m., 8 p.m.) across five consecutive days in 33 children with ADHD (22 with and 11 without oppositional defiant disorder; ODD) and 33 class- and sex-matched controls (aged 6-12). The cortisol awakening response (increase from awakening to 30 min after awakening) and the diurnal cortisol profile (across-the-day variations) were compared for ADHD with ODD (ADHD + ODD) and without ODD (ADHD) subgroups and the control group. RESULTS: The cortisol awakening response was not significantly different between groups. However, longitudinal analyses to evaluate cortisol profiles across the day revealed a significant Group * Time effect (p < .001). More specifically, compared to each other, the ADHD subgroup showed a flatter slope with relative morning hypo-arousal and evening hyperarousal, whereas the ADHD + ODD subgroup showed a steeper slope with relative morning hyperarousal and evening hypo-arousal (p < .001). CONCLUSIONS: Findings support time-related arousal disruptions in children with ADHD associated with the presence or absence of ODD comorbidity. We recommend research on cortisol in larger samples for a better understanding of arousal mechanisms involved in ADHD not only with and without ODD but also with other comorbidities which may have implications for timing of arousal-based treatments. PMID- 22324290 TI - Evaluation of hepatic glucose metabolism via gluconeogenesis and glycogenolysis after oral administration of insulin nanoparticles. AB - Nanoparticles were designed to promote insulin intestinal absorption via the oral route, to increase portal insulin levels to better mimic the physiological pathway, providing enhanced glucose control through glycogenolysis and gluconeogenesis. Nanoparticles were formulated with insulin encapsulated in the core material consisting of alginate and dextran sulfate, associated with poloxamer and subsequently coated with chitosan then albumin. A spherical and slightly rough core was observed in electron micrographs with the appearance of a concentration gradient of the polysaccharide structure toward the periphery of the nanoparticle. Atomic force microscopy showed that the fully formed nanoparticles are about 200 nm in diameter with smooth and spherical morphology. Histopathological analysis of organs and tissues of diabetic rats dosed daily for 15 days with insulin nanoparticles was used to evaluate toxicological issues. No morphological or pathological alterations were observed in rat liver, spleen, pancreas, kidney or intestinal sections. Following, the effect of nanoencapsulated insulin on inhibiting hepatic gluconeogenesis was evaluated after a single insulin administration and oral glucose tolerance test, which represents a significant metabolic challenge to the liver. Alterations in the hepatic glucose metabolism of fasted streptozotocin-diabetic rats were determined by the percent contribution of glycogenolysis and gluconeogenesis, measured by using metabolic tracers, however similar gluconeogenesis contribution to the hepatic metabolism was observed between diabetic rats receiving nanoencapsulated insulin or insulin solution. The metabolic results may be explained by the inability of a single dose in shifting the gluconeogenesis/glycogenolysis contributions, sampling time, fasting period or by influence of the kidney enzymes and impairment in insulin signaling observed in stz-diabetic rats. PMID- 22324291 TI - Protein quantitation using Ru-NHS ester tagging and isotope dilution high pressure liquid chromatography-inductively coupled plasma mass spectrometry determination. AB - An accurate, simple, and sensitive method for the direct determination of proteins by nonspecies specific isotope dilution and external calibration high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS) is described. The labeling of myoglobin (17 kDa), transferrin (77 kDa), and thyroglobulin (670 kDa) proteins was accomplished in a single-step reaction with a commercially available bis(2,2'-bipyridine)-4'-methyl-4 carboxybipyridine-ruthenium N-succinimidyl ester-bis(hexafluorophosphate) (Ru-NHS ester). Using excess amounts of Ru-NHS ester compared to the protein concentration at optimized labeling conditions, constant ratios for Ru to proteins were obtained. Bioconjugate solutions containing both labeled and unlabeled proteins as well as excess Ru-NHS ester reagent were injected onto a size exclusion HPLC column for separation and ICPMS detection without any further treatment. A (99)Ru enriched spike was used for nonspecies specific ID calibration. The accuracy of the method was confirmed at various concentration levels. An average recovery of 100% +/- 3% (1 standard deviation (SD), n = 9) was obtained with a typical precision of better than 5% RSD at 100 MUg mL(-1) for nonspecies specific ID. Detection limits (3SD) of 1.6, 3.2, and 7.0 fmol estimated from three procedure blanks were obtained for myoglobin, transferrin, and thyroglobulin, respectively. These detection limits are suitable for the direct determination of intact proteins at trace levels. For simplicity, external calibration was also tested. Good linear correlation coefficients, 0.9901, 0.9921, and 0.9980 for myoglobin, transferrin, and thyroglobulin, respectively, were obtained. The measured concentrations of proteins in a solution were in good agreement with their volumetrically prepared values. To the best of our knowledge, this is the first application of nonspecies specific ID for the accurate and direct determination of proteins using a Ru-NHS ester labeling reagent. PMID- 22324292 TI - Glycated Hemoglobin A(1c) as screening for diabetes mellitus in HIV-infected individuals. AB - The American Diabetes Association now recommends hemoglobin A(1c) (HbA(1c)) screening for the diagnosis of diabetes. It has been reported that HbA(1c) levels underestimate glycemic levels in HIV-infected persons. We examined the performance of HbA(1c) as a screening test for diabetes in a group of HIV infected people without diabetes. We conducted a retrospective cross-sectional cohort study among HIV-infected patients determining the sensitivity and specificity of HbA(1c) as a screening test compared to fasting blood glucose (FBG). The effect of treatment regimen on the relationship between HbA(1c) and FBG was assessed by multiple linear regressions. Twenty-two of the 395 patients included in the study were newly diagnosed with diabetes based on FBG>=126 mg/dL. Using a cutoff of HbA(1c)>=6.5%, HbA(1c) had a sensitivity of 40.9% and specificity of 97.5% for identification of incident diabetes. At an HbA(1c) level of 5.8% the product of sensitivity and specificity was maximized, with values of 88.8% and 77.5% respectively. Higher mean cell volume (MCV) values (p=0.02) and current use of a non-nucleoside reverse transcriptase inhibitors (NNRTIs; p=0.02) significantly increased the slope, while PI use significantly decreased the slope (p<0.001), of the linear regression of HbA(1c) compared to FBG. Tenofovir use did not significantly alter the slope or y-intercept of the line. Among HIV-infected nondiabetic patients, HbA(1c) is insensitive, although highly specific for diagnosing diabetes. Current antiretroviral (ART) use has significant and variable influence on the relationship between HbA(1c) and FBG. The use of HbA(1c) in conjunction with FBG may be the best modality to screen for diabetes. PMID- 22324293 TI - Surfaces with self-repairable ultrahydrophobicity based on self-organizing freely floating colloidal particles. AB - We report an approach for the design of materials with self-repairable ultrahydrophobic properties. The materials are based on highly fluorinated crystalline fusible wax with incorporated colloidal particles. Due to the highly pronounced tendency of the wax to crystallize, the formation of blends with rough fractal surfaces was observed. In order to prove their self-repairing ability, we mechanically damaged them by scratching, which removed most of the particles from the surface. Melting of the damaged blend resulted in reorganization of the particles at the wax-air interface, restoring the initial structure and thus the ultrahydrophobic behavior. PMID- 22324294 TI - D-Galactose uptake is nonfunctional in the conidiospores of Aspergillus niger. AB - The majority of black Aspergilli (Aspergillus section Nigri), including Aspergillus niger, as well as many other Ascomycetes fail to germinate on d galactose as a sole carbon source. Here, we provide evidence that the ability of A. niger to transport D-galactose is growth stage dependent, being absent in the conidiospores but present in the mycelia. Despite earlier claims, we could identify galactokinase activity in growing cells and all genes of the Leloir pathway (responsible for channelling D-galactose into the EMP pathway) are well induced on D-galactose (and also on lactose, D-xylose and L-arabinose) in the mycelial stage. Expression of all Leloir pathway genes was also detectable in conidiospores, although galE (encoding a galactokinase) and galD (encoding a galactose-1-phosphate uridylyl transferase) were expressed poorly. These results suggest that the D-galactose-negative phenotype of A. niger conidiospores may be due to the lack of inducer uptake. PMID- 22324295 TI - Use estimates of in-feed antimicrobials in swine production in the United States. AB - When considering the development of antimicrobial resistance in food animals, comparing gross use estimates of different antimicrobials is of little value due to differences in potencies, duration of activity, relative effect on target and commensal bacteria, and mechanisms of resistance. However, it may be valuable to understand quantities of different antimicrobials used in different ages of swine and for what applications. Therefore, the objective of this project was to construct an estimate of antimicrobial use through the feed in swine production in the United States. Estimates were based on data from the National Animal Health Monitoring System (NAHMS) Swine 2006 Study and from a 2009 survey of swine exclusive practitioners. Inputs consisted of number of pigs in a production phase, feed intake per day, dose of the antimicrobial in the feed, and duration of administration. Calculations were performed for a total of 102 combinations of antimicrobials (n=17), production phases (n=2), and reasons for use (n=3). Calculations were first conducted on farm-level data, and then extrapolated to the U.S. swine population. Among the nursery phase estimates, chlortetracycline had the largest estimate of use, followed by oxytetracycline and tilmicosin. In the grower/finisher phase, chlortetracycline also had the largest use estimate, followed by tylosin and oxytetracycline. As an annual industry estimate for all phases, chlortetracycline had the highest estimated use at 533,973 kg. The second and third highest estimates were tylosin and oxytetracycline with estimated annual uses of 165,803 kg and 154,956 kg, respectively. The estimates presented here were constructed to accurately reflect available data related to production practices, and to provide an example of a scientific approach to estimating use of compounds in production animals. PMID- 22324296 TI - 1,3-Dipolar cycloaddition of 2,6-dichlorobenzonitrile oxide to 2-methyl-N confused porphyrin. Regio- and stereoselective synthesis and structural characterization of 2-aza-21-carbabacteriochlorin and resolution of 2-aza-21 carbachlorin enantiomers. AB - The 1,3-dipolar cycloaddition reaction of 2-methyl-N-confused porphyrin with 2,6 dichlorobenzonitrile oxide yielded four isomeric monoadducts of carbachlorin type and one diadduct of carbabacteriochlorin type. Two major carbachlorin products, constituting 82% of the monoadducts, were shown to be structural precursors of the unique 2-aza-21-carbabacteriochlorin. Enantiomers of the most abundant isomer of 2-aza-21-carbachlorin (55% of all carbachlorin products) have been resolved. The crystal structures of 2-aza-21-carbabacteriochlorin and the most abundant isomer of 2-aza-21-carbachlorin were characterized by X-ray diffraction. PMID- 22324297 TI - Comparison of the GlideScope(r) videolaryngoscope and the Macintosh laryngoscope for double-lumen tube intubation. AB - Intubation with a double-lumen tube is important for achieving one-lung ventilation and facilitating thoracic surgery. The GlideScope((r)) videolaryngoscope (Verathon Inc., Bothell, WA, USA) is designed to assist tracheal intubation for patients with a difficult airway. We wished to compare the GlideScope and direct laryngoscopy for double-lumen tube intubation. Sixty adult patients requiring a double-lumen tube for thoracic surgery and predicted uncomplicated laryngoscopy were randomly assigned to a direct Macintosh laryngoscopy group (n = 30) or a GlideScope group (n = 30). The mean (SD) duration of intubation was longer in the Macintosh group (62.5 (29.7) s) than in the GlideScope group (45.6 (10.7) s; p = 0.007). There was no difference in the success of the first attempt at intubation (26/30 (87%) and 30/30 (100%) for Macintosh and GlideScope groups, respectively; p = 0.112). The incidence of sore throat and hoarseness was higher in the Macintosh group (18 (60%) and 14 (47%), respectively) than in the GlideScope group (6 (20%) and 4 (13%), respectively; p = 0.003 and 0.004). We conclude that double-lumen tube intubation in patients with predicted normal laryngoscopy is easier using the GlideScope videolaryngoscope than the Macintosh laryngoscope. PMID- 22324298 TI - Redefining the natural history of calcific aortic stenosis: lessons from Laennec. PMID- 22324299 TI - Compression of molecular interaction fields using wavelet thumbnails: application to molecular alignment. AB - Molecular interaction fields provide a useful description of ligand binding propensity and have found widespread use in computer-aided drug design, for example, to characterize protein binding sites and in small molecular applications, such as three-dimensional quantitative structure-activity relationships, physicochemical property prediction, and virtual screening. However, the grids on which the field data are stored are typically very large, consisting of thousands of data points, which make them cumbersome to store and manipulate. The wavelet transform is a commonly used data compression technique, for example, in signal processing and image compression. Here we use the wavelet transform to encode molecular interaction fields as wavelet thumbnails, which represent the original grid data in significantly reduced volumes. We describe a method for aligning wavelet thumbnails based on extracting extrema from the thumbnails and subsequently use them for virtual screening. We demonstrate that wavelet thumbnails provide an effective method of capturing the three-dimensional information encoded in a molecular interaction field. PMID- 22324300 TI - Post-transplant lymphoproliferative diseases in Asian solid organ transplant recipients: late onset and favorable response to treatment. AB - Nineteen consecutive patients with post-transplant lymphoproliferative disorders (PTLD) in an Asian population were reviewed. The histopathologic diagnoses were monomorphic (CD20-positive diffuse large B-cell lymphoma, n = 14); plasmacytic (n = 1); Burkitt-like (n = 1); natural killer cell lymphoma (n = 1); lymphomatoid papulosis (n = 1); and classical Hodgkin lymphoma (n = 1). Early-onset ( 98% before and after administration; P = 0.0336), which was accompanied by higher proportions of Firmicutes and Fusobacteria. FISH confirmed this decrease in gastric Helicobacter (P < 0.0001) and showed an increase in total bacteria in the duodenum (P = 0.0033) during omeprazole. However, Unifrac analysis showed that omeprazole administration did not significantly alter the overall phylogenetic composition of the gastric and duodenal microbiota. In feces, qPCR showed an increase in Lactobacillus spp. during omeprazole (P < 0.0001), which was accompanied by a lower abundance of Faecalibacterium spp. and Bacteroides-Prevotella-Porphyromonas in the male dogs. This study suggests that omeprazole administration leads to quantitative changes in GI microbiota of healthy dogs. PMID- 22324306 TI - Effects of a hypercaloric diet on beta-cell responsivity in lean healthy men. AB - OBJECTIVE: Insulin resistance and hyperinsulinaemia precede the onset of obesity induced DM2. The early adaptation of the beta-cell during the initial phase of overfeeding and weight gain has only been partly elucidated. We studied the early changes in insulin clearance and beta-cell responsivity during a positive and negative energy balance in lean healthy men. DESIGN: We studied in nine healthy lean men [age, 37 (27-43) years; BMI, 23.6 (20.6-25.6) kg/m(2) ] insulin sensitivity, insulin clearance, insulin secretion and static and dynamic beta cell responsivity at baseline and after the hypercaloric and subsequent hypocaloric diet. RESULTS: Participants gained 7 [5.1-7.6]% of their initial body weight on the hypercaloric diet. Compared to baseline, insulin sensitivity and insulin clearance decreased, while glucose-stimulated insulin secretion was higher. The GLP-1 response to oral glucose did not change. The dynamic beta-cell responsivity index increased but the basal and static responsivity indexes did not change. Total and static disposition indexes (DIs) in the hypercaloric state showed a trend towards a decrease. During the hypocaloric diet, insulin sensitivity, glucose-stimulated insulin secretion and insulin clearance returned to baseline. The responsivity and the DIs were not different in the hypocaloric phase compared to baseline. CONCLUSION: A positive energy balance resulting in weight gain in lean men induces hyperinsulinaemia, which is explained by a combined effect on insulin clearance and insulin secretion. Increased insulin secretion was related to insulin resistance-induced higher glucose concentrations but also to increased dynamic beta-cell responsivity. Glucose sensitivity of the beta-cell did not change. These early adaptations are completely reversible during a negative energy balance after loss of the gained weight. PMID- 22324307 TI - Blood clearance and biodistribution of polymer brush-afforded silica particles prepared by surface-initiated living radical polymerization. AB - The physiological properties of polymer brush-afforded silica particles prepared by surface-initiated living radical polymerization were investigated in terms of the circulation lifetime in the blood and distribution in tissues. Hydrophilic polymers consisting mainly of poly(poly(ethylene glycol) methyl ether methacrylate) were grafted onto silica particles by surface-initiated atom transfer radical polymerization that was mediated by a copper complex to produce hairy hybrid particles. A series of hybrid particles was synthesized by varying the diameter of the silica core and the chain length of the polymer brush to examine the relationship between their physicochemical and physiological properties. The hybrid particles were injected intravenously into mice to investigate systematically their blood clearance and body distribution. It was revealed that the structural features of the hybrid particles significantly affected their in vivo pharmacokinetics. Some hybrid particles exhibited an excellently prolonged circulation lifetime in the blood with a half life of ~20 h. When such hybrid particles were injected intravenously into a tumor-bearing mouse, they preferentially accumulated in tumor tissue. The tumor-targeted delivery was optically visualized using hybrid particles grafted with fluorescence-labeled polymer brushes. PMID- 22324308 TI - On the origin of regio- and stereoselectivity in singlet oxygen addition to enecarbamates. AB - The reactions of excited state singlet molecular oxygen ((1)Delta(g),(1)O(2)) continue to witness interesting new developments. In the most recent manifestation, (1)O(2) is tamed to react with enecarbamates in a stereoselective manner, which is remarkable, in view of its inherently high reactivity (Acc. Chem. Res. 2008, 41, 387). Herein, we employed the CAS-MP2(8,7)/6-31G* as well as the CAS-MP2(10,8)/6-31G* computations to unravel the origin of (i) diastereoselectivities in dioxetane or hydroperoxide formation and (ii) regioselectivity leading to a [2 + 2] cycloadduct or an ene product when (1)O(2) reacts with an oxazolidinone tethered 2-phenyl-1-propenyl system. The computed Gibbs free energy profiles for E- and Z-isomers when (1)O(2) approaches through the hindered and nonhindered diastereotopic faces (by virtue of chiral oxazolidinone) of the enecarbamates exhibit distinct differences. In the case of E-isomer, the relative energies of the transition structures responsible for hydroperoxide (ene product) are lower than that for dioxetane formation. On the other hand, the ene pathway is predicted to involve higher barriers as compared to the corresponding dioxetane pathway for Z-isomer. The energy difference between the rate-determining diastereomeric transition structures involved in the most favored ene reaction for E-enecarbamate suggests high diastereoselectivity. In contrast, the corresponding energy difference for Z-enecarbamate in the ene pathway is found to be diminishingly close, implying low diastereoselectivity. However, the dioxetane formation from Z-enecarbamate is predicted to exhibit high diastereoselectivity. The application of activation strain model as well as the differences in stereoelectronic effects in the stereocontrolling transition structures is found to be effective toward rationalizing the origin of selectivities reported herein. These predictions are found to be in excellent agreement with the experimental observations. PMID- 22324309 TI - On-plate selective enrichment and self-desalting of peptides/proteins for direct MALDI MS analysis. AB - In this paper, a new technique has been proposed to achieve simultaneous peptides/proteins enrichment and wash-free self-desalting on a novel sample support with a circle hydrophobic-hydrophilic-hydrophobic pattern. Upon deposition, the sample solution is first concentrated in a small area by repulsion of the hydrophobic outer layer, and then, the peptides/proteins and coexisting salt contaminants are selectively captured in different regions of the pattern through strong hydrophobic and hydrophilic attractions, respectively. As a result, the detection sensitivity is improved by 2 orders of magnitude better than the use of the traditional MALDI plate, and high-quality mass spectra are obtained even in the presence of NaCl (1 M), NH(4)HCO(3) (100 mM), or urea (1 M). The practical application of this method is further demonstrated by the successful analysis of myoglobin digests with high sequence coverage, demonstrating the great potential in proteomic research. PMID- 22324310 TI - Manipulation of collective optical activity in one-dimensional plasmonic assembly. AB - The manipulation of the chirality and corresponding optical activity in the visible-near-infrared (NIR) light region is significant to realize applications in the fields of chemical sensing, enantioselective separation, chiral nanocatalysis, and optical devices. We studied the plasmon-induced circular dichroism (CD) response by one-dimensional (1D) assembly of cysteine (CYS) and gold nanorods (GNRs). Typically, GNRs can form end-to-end assembly through the electrostatic attraction of CYS molecules preferentially attached on the ends of different GNRs. CD responses are observed at both the UV and visible-NIR light region in the 1D assembly, which are assigned to the CYS molecules and the GNRs, respectively. In addition, the wavelength of the CD responses can be manipulated from 550 nm to more than 900 nm through altering the aspect ratios of GNRs in 1D assembly. Anisotropic enhancement of optical activity is discovered, suggesting that the enhancement of the longitudinal localized surface plasmon resonance (LSPR) peak of GNRs in the CD response is much more apparent than that of the transverse LSPR. The CD responses of individual CYS-attached GNRs and CYS assembled gold nanoparticles (GNPs) substantiate that the form of assembly and the shape of building blocks are significant not only for the intensity but for the line shape of the CD signals. PMID- 22324311 TI - Detection of nano-oxidation sites on the surface of hemoglobin crystals using tip enhanced Raman scattering. AB - Hemoglobin nanocrystals were analyzed with tip-enhanced Raman scattering (TERS), surface-enhanced resonance Raman scattering (SERRS) and conventional resonance Raman scattering (RRS) using 532 nm excitation. The extremely high spatial resolution of TERS enables selective enhancement of heme, protein, and amino acid bands from the crystal surface not observed in the SERRS or RRS spectra. Two bands appearing at 1378 and 1355 cm(-1) assigned to the ferric and ferrous oxidation state marker bands, respectively, were observed in both TERS and SERRS spectra but not in the RRS spectrum of the bulk sample. The results indicate that nanoscale oxidation changes are occurring at the hemoglobin crystal surface. These changes could be explained by oxygen exchange at the crystal surface and demonstrate the potential of the TERS technique to obtain structural information not possible with conventional Raman microscopy. PMID- 22324312 TI - AC electrokinetic templating of colloidal particle assemblies: effect of electrohydrodynamic flows. AB - The use of spatially nonuniform electric fields for the contact-free colloidal particle assembly into ordered structures of various length scales is a research area of great interest. In the present work, numerical simulations are undertaken in order to advance our understanding of the physical mechanisms that govern this colloidal assembly process and their relation to the electric field characteristics and colloidal system properties. More specifically, the electric field driven assembly of colloidal silica (d(p) = 0.32 and 2 MUm) in DMSO, a near index matching fluid, is studied numerically over a range of voltages and concentration by means of a continuum thermodynamic approach. The equilibrium (u(f) = 0) and nonequilibrium (u(f) ? 0) cases were compared to determine whether fluid motion had an effect on the shape and size of assemblies. It was found that the nonequilibrium case was substantially different versus the equilibrium case, in both size and shape of the assembled structure. This dependence was related to the relative magnitudes of the electric-field driven convective motion of particles versus the fluid velocity. Fluid velocity magnitudes on the order of mm/s were predicted for 0.32 MUm particles at 1% initial solids content, and the induced fluid velocity was found to be larger at the same voltage/initial volume fraction as the particle size decreased, owing to a larger contribution from entropic forces. PMID- 22324313 TI - Galectin-9: a suppressor of food allergy? PMID- 22324314 TI - Practical guide to skin prick tests in allergy to aeroallergens: some concerns. PMID- 22324315 TI - MALDI-TOF MS analysis of ribosomal proteins coded in S10 and spc operons rapidly classified the Sphingomonadaceae as alkylphenol polyethoxylate-degrading bacteria from the environment. AB - Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) using ribosomal subunit proteins coded in the S10-spc-alpha operon as biomarkers was applied for the classification of the Sphingomonadaceae from the environment. To construct a ribosomal protein database, S10-spc-alpha operon of type strains of the Sphingomonadaceae and their related alkylphenol polyethoxylate (APEO(n) )-degrading bacteria were sequenced using specific primers designed based on nucleotide sequences of genome-sequenced strains. The observed MALDI mass spectra of intact cells were compared with the theoretical mass of the constructed ribosomal protein database. The nine selected biomarkers coded in the S10-spc-alpha operon, L18, L22, L24, L29, L30, S08, S14, S17, and S19, could successfully distinguish the Sphingopyxis terrae NBRC 15098(T) and APEO(n) -degrading bacteria strain BSN20, despite only one base difference in the 16S rRNA gene sequence. This method, named the S10-GERMS (S10-spc-alpha operon gene-encoded ribosomal protein mass spectrum) method, is a significantly useful tool for bacterial discrimination of the Sphingomonadaceae at the strain level and can detect and monitor the main APEO(n) -degrading bacteria in the environment. PMID- 22324316 TI - Aetiology for the covariation between combined type ADHD and reading difficulties in a family study: the role of IQ. AB - BACKGROUND: Twin studies using both clinical and population-based samples suggest that the frequent co-occurrence of attention deficit hyperactivity disorder (ADHD) and reading ability/disability (RD) is largely driven by shared genetic influences. While both disorders are associated with lower IQ, recent twin data suggest that the shared genetic variability between reading difficulties and ADHD inattention symptoms is largely independent from genetic influences contributing to general cognitive ability. The current study aimed to extend the previous findings that were based on rating scale measures in a population sample by examining the generalisability of the findings to a clinical population, and by measuring reading difficulties both with a rating scale and with an objective task. This study investigated the familial relationships between ADHD, reading difficulties and IQ in a sample of individuals diagnosed with ADHD combined type, their siblings and control sibling pairs. METHODS: Multivariate familial models were run on data from 1,789 individuals at ages 6-19. Reading difficulties were measured with both rating scale and an objective task. IQ was obtained using the Wechsler Intelligence Scales (WISC-III/WAIS-III). RESULTS: Significant phenotypic (.2-.4) and familial (.3-.5) correlations were observed among ADHD, reading difficulties and IQ. Yet, 53%-72% of the overlapping familial influences between ADHD and reading difficulties were not shared with IQ. CONCLUSIONS: Our finding that familial influences shared with general cognitive ability, although present, do not account for the majority of the overlapping familial influences on ADHD and reading difficulties extends previous findings from a population-based study to a clinically ascertained sample with combined type ADHD. PMID- 22324317 TI - A novel alpha(0) -thalassemia deletion in a Greek patient with HbH disease and beta-thalassemia trait. AB - OBJECTIVES: To determine the molecular basis in a Greek child suspected of having HbH disease and beta-thalassemia trait. METHODS: Standard hematology, Hb electrophoresis, and HPLC. Multiplex ligation-dependent probe amplification (MLPA), direct sequencing, and breakpoint characterization by NimbleGen fine tiling array analysis. RESULTS: The index patient showed a moderate microcytic hypochromic anemia with normal ZPP and elevated HbA(2) , indicative for beta thalassemia trait. However, the moderate microcytic hypochromic anemia along with the observation of HbH inclusions in occasional red blood cells suggested a coexisting alpha-thalassemia. Molecular analysis indicated that the propositus inherited the beta(+) -thalassemia mutation IVS2-745 (c>g) and a novel alpha(0) thalassemia deletion from the mother, and the common non-deletion alpha thalassemia allele alpha(2) (-5nt)alpha from the father. The alpha(0) thalassemia deletion, named - -(BGS) , is approximately 131.6 kb in length. It removes the major regulatory elements along with the functional alpha-globin genes but leaves the theta-gene intact. CONCLUSIONS: The compound interaction of a beta-thalassemia defect along with a single functional alpha-globin gene is quite rare. Although patients with HbH/beta-thal and simple HbH disease have comparable levels of Hb, the absence of free beta-globin chains and thus detectable non-functional HbH means that in HbH/beta-thal, the levels of functional Hb are higher, resulting in a better compensated functional anemia. Rare large deletions as the one described here remain undetected by gap-PCR in routine molecular screening. The introduction of MLPA as a diagnostic screening tool may improve laboratory diagnostics for these defects. The use of NimbleGen fine-tiling arrays may give additional information about the precise location of breakpoints. PMID- 22324318 TI - The plasma level of soluble receptor for advanced glycation end products is decreased in patients with systemic lupus erythematosus. AB - In recent years, the role of high mobility group box-1 (HMGB1) protein and its receptors in autoimmune diseases has received increasing attention. It has been documented that HMGB1 is associated with disease activity in patients with systemic lupus erythematosus (SLE). This study was undertaken to determine the potential role of receptor for advanced glycation end products (RAGE), one receptor for HMGB1, in the pathogenesis of SLE. Plasma levels of soluble RAGE (sRAGE) from 105 patients with clinical diagnosis of SLE and 43 healthy controls were determined by ELISA. Associations between sRAGE levels and clinical, laboratory characteristics were assessed. The data showed that plasma levels of sRAGE in patients with SLE were significantly lower than those in healthy controls (HC) (P = 0.003). Plasma sRAGE in patients receiving short-period treatment showed an immediate decrease compared with the untreated patients (P = 0.023). In contrast, plasma sRAGE in patients receiving long-period treatment were significantly increased compared to those with short-period treatment (P = 0.000) and comparable with those in HC (P = 0.305). The significant decreased levels of sRAGE in patients with SLE suggest the potential association of RAGE signalling and SLE clinical pathology, whereas, long-period antilupus treatment may counteract the decreased sRAGE levels in patients with SLE. PMID- 22324319 TI - The effect of posture and anaesthetic technique on the surgical pleth index. AB - The surgical pleth index has been shown to correlate with surrogate variables of nociception during general anaesthesia, and it has been suggested to be of use as a depth of anaesthesia monitor. However, little is known about confounding factors. As the main determining variables are based on both central and peripheral autonomic regulatory mechanisms, we hypothesised that changing a patient's posture may produce a marked effect. We studied the effects of posture change in 45 patients who were randomly assigned to receive general (n = 15) or spinal anaesthesia with (n = 15) or without sedation (n = 15), as well as 15 awake volunteers. Mean (SD) values of the surgical pleth index after adoption of the lithotomy position were reduced from 57 (22) to 21 (6) under general anaesthesia, 63 (15) to 31 (9) under spinal anaesthesia alone, and 52 (14) to 22 (8) under spinal anaesthesia with sedation (all p < 0.01). In healthy volunteers, the surgical pleth index increased from 37 (13) to 57 (11) (p < 0.01) after 30 degrees head-up tilt and was reduced from 35 (11) to 25 (11) after head-down tilt (p < 0.05). Change in posture has a marked effect on the surgical pleth index which lasts for at least 45 min, and this must be considered when interpreting the displayed values. PMID- 22324320 TI - 3D reconstruction of the glycocalyx structure in mammalian capillaries using electron tomography. AB - OBJECTIVE: Visualising the molecular strands making up the glycocalyx in the lumen of small blood vessels has proved to be difficult using conventional transmission electron microscopy techniques. Images obtained from tissue stained in a variety of ways have revealed a regularity in the organisation of the proteoglycan components of the glycocalyx layer (fundamental spacing about 20 nm), but require a large sample number. Attempts to visualise the glycocalyx face on (i.e. in a direction perpendicular to the endothelial cell layer in the lumen and directly applicable for permeability modelling) has had limited success (e.g. freeze fracture). A new approach is therefore needed. METHODS: Here we demonstrate the effectiveness of using the relatively novel electron microscopy technique of 3D electron tomography on two differently stained glycocalyx preparations. A tannic acid staining method and a novel staining technique using Lanthanum Dysprosium Glycosamino Glycan adhesion (the LaDy GAGa method). RESULTS: 3D electron tomography reveals details of the architecture of the glycocalyx just above the endothelial cell layer. The LaDy GAGa method visually appears to show more complete coverage and more depth than the Tannic Acid staining method. CONCLUSION: The tomographic reconstructions show a potentially significant improvement in determining glycocalyx structure over standard transmission electron microscopy. PMID- 22324321 TI - Pathological conditions involving extracellular hemoglobin: molecular mechanisms, clinical significance, and novel therapeutic opportunities for alpha(1) microglobulin. AB - Hemoglobin (Hb) is the major oxygen (O(2))-carrying system of the blood but has many potentially dangerous side effects due to oxidation and reduction reactions of the heme-bound iron and O(2). Extracellular Hb, resulting from hemolysis or exogenous infusion, is shown to be an important pathogenic factor in a growing number of diseases. This review briefly outlines the oxidative/reductive toxic reactions of Hb and its metabolites. It also describes physiological protection mechanisms that have evolved against extracellular Hb, with a focus on the most recently discovered: the heme- and radical-binding protein alpha(1)-microglobulin (A1M). This protein is found in all vertebrates, including man, and operates by rapidly clearing cytosols and extravascular fluids of heme groups and free radicals released from Hb. Five groups of pathological conditions with high concentrations of extracellular Hb are described: hemolytic anemias and transfusion reactions, the pregnancy complication pre-eclampsia, cerebral intraventricular hemorrhage of premature infants, chronic inflammatory leg ulcers, and infusion of Hb-based O(2) carriers as blood substitutes. Finally, possible treatments of these conditions are discussed, giving a special attention to the described protective effects of A1M. PMID- 22324323 TI - A mixed method approach to clarify the construct validity of interprofessional collaboration: an empirical research illustration. AB - The rapid development of empirical studies in the field of interprofessional collaboration (IPC) calls for a wide array of scientific approaches ranging from recruitment and motivation to measurement and design questions. Regardless of whether researchers choose qualitative or quantitative approaches, they must substantiate their findings. We argue that more attention should be given to reliability and validity issues to improve our understanding of IPC as a phenomenon and practice. A mixed methods approach is presented as a relevant design format for the study of IPC. This paper aims to argue that a combination of methodologies may be a feasible way to enhance our understanding of IPC, with a special focus on reliability and validity issues; illustrate the application of different methodologies in an IPC research project; and emphasize the distinction between validity and validation to mitigate possible obstacles in integrating qualitative and quantitative research in the study of IPC. PMID- 22324324 TI - Policy analysis at ES&T. PMID- 22324325 TI - Development of a biostable replacement for PEGDA hydrogels. AB - The exceptional tunability of poly(ethylene glycol) (PEG) hydrogel chemical, mechanical, and biological properties enables their successful use in a wide range of biomedical applications. Although PEG diacrylate (PEGDA) hydrogels are often used as nondegradable controls in short-term in vitro studies, it is widely acknowledged that the hydrolytically labile esters formed upon acrylation of the PEG diol make them susceptible to slow degradation in vivo. A PEG hydrogel system that maintains the desirable properties of PEGDA while improving biostability would be valuable in preventing degradation-related failure of gel-based devices in long-term in vivo applications. To this end, PEG diacrylamide (PEGDAA) hydrogels were synthesized and characterized in quantitative comparison to traditional PEGDA hydrogels. It was found that PEGDAA hydrogel modulus and swelling can be tuned over a similar range and to comparable degrees as PEGDA hydrogels with changes in macromer molecular weight and concentration. Additionally, PEGDAA cytocompatibility, low cell adhesion, and capacity for incorporation of bioactivity were analogous to that of PEGDA. In vitro hydrolytic degradation studies showed that the amide-based PEGDAA had significantly increased biostability relative to PEGDA. Overall, these findings indicate that PEGDAA hydrogels are a suitable replacement for PEGDA hydrogels with enhanced hydrolytic resistance. In addition, these studies provide a quantitative measure of the hydrolytic degradation rate of PEGDA hydrogels which was previously lacking in the literature. PMID- 22324326 TI - The influence of the structure and the composition of water/AOT-Tween 85/IPM microemulsion system on transdermal delivery of 5-fluorouracil. AB - The purpose of this study was to investigate the influence of the structure and the composition of water/Aerosol-OT (AOT)-Tween 85/isopropylmyristate (IPM) microemulsion system (WATI) on transdermal delivery of 5-fluorouracil (5-FU). The structure of WATI was characterized by measuring surface tension, density, viscosity, electric conductivity, and differential scanning calorimetry. The effect of the drug loading, water content, component compositions and the amount of mixed surfactant on permeation of 5-FU through mice skin was evaluated by using Franz-type diffusion cells. The results in vitro implied that WATI was W/O microemulsion when the water content was below 20 wt% at fixed 20 wt% of mixed surfactant at 25 degrees C, then might be transformed to a bicontinuous structure, finally, formed O/W microemulsion with water content over 30 wt%. Increase of the drug loading can directly facilitate the penetration of the drug across the skin. Drug diffusion after 12 h from the bicontinuous microemulsion (795.1 +/- 22.3 ug.cm(-2)) would be fastest compared to that from the W/O microemulsion (650.2 +/- 11.7 ug.cm(-2)) and the O/W microemulsion (676.6 +/- 14.8 ug.cm(-2)). The combination of AOT and IPM could bring about synergistic effect on the skin enhancement, however, Tween 85 in WATI decreased the cumulative permeation amount of 5-FU. The content of mixed surfactant had no effect on the permeation of 5-FU at fixed surfactant/cosurfactant ratio (K(m) = 2). Thus, the increased transdermal delivery the hydrophilic drug of 5-FU was found to be concerned with both of the structure and the composition of WATI. PMID- 22324327 TI - Can aging with disability find a home in gerontological social work? PMID- 22324328 TI - A long life with a particular signature: life course and aging for people with disabilities. AB - What does it mean to live a long life and grow old with disabilities? Or to be an aging parent and still be a caregiver to a disabled adult child? These are questions discussed in this article, the aim of which is to show how a life course perspective adds insight to the lived experience of disability and ageing of adults with disabilities. It is argued that the time concept is fundamental to the understanding of the lives of disabled people. Results are presented which challenge established knowledge regarding disability policies, autonomy, body, biographical disruption and prerequisites of active aging. PMID- 22324329 TI - Accelerating the translation of research into practice in long term services and supports: a critical need for federal infrastructure at the nexus of aging and disability. AB - The nexus of aging and disability, characterized by the phenomenon of aging with a disability, will become more visible as the population ages and the number of people with disabilities surviving to midlife increases. This article addresses 3 interrelated issues critical to the fields of aging and disability: increasing demand for community-based long-term services and supports, a paucity of evidence based programs demonstrating effectiveness in facilitating independence for those aging with a disability, and lack of a federal infrastructure to support coordinated investments in research-to-practice for this population. Suggestions for federal interagency collaborations are given, along with roles for key stakeholders. PMID- 22324330 TI - Indicators of a balanced long-term service and support system: examining the impact on individuals aging with a lifelong disability. AB - This article explores how rebalancing efforts can support the needs of individuals aging with a lifelong disability. The National Balancing Indicator project examined the overall long-term supports and services system (LTSS) progress in five indicators within the Sustainability, Coordination and Transparency, and Prevention principles toward a balanced LTSS system for those aging with a lifelong disability. In assessing state efforts to create a balanced participant-directed LTSS system with the National Balancing Indicators, the findings suggest states are better equipping the system to handle a burgeoning population of individuals aging with a lifelong disability, but more progress is still needed. Overall, states need to continue to create a seamless system that allows individuals with lifelong disabilities to transition smoothly through the life course. PMID- 22324331 TI - Consumer direction in long-term care policy: overcoming barriers to promoting older adults' opportunity for self-direction. AB - There has been a growing trend in long-term care policy to offer individuals with disabilities the option of consumer direction (CD), where responsibility of managing care and support services is transferred from agencies to care recipients, thus supporting clients' self-determination. Although CD has been accepted as an option for non-elderly individuals with disabilities, barriers persist to promoting older adults' autonomy through CD. This article reviews the incorporation of CD in long-term care policy, addresses the current barriers to providing older adults the right to self-direct, and makes recommendations for overcoming these barriers through social work practice, policy, and research. PMID- 22324332 TI - Impact of a multicomponent support services program on informal caregivers of adults aging with disabilities. AB - A multicomponent support services program was implemented for veterans aging with disabilities and their informal caregivers (n = 42 dyads). Caregiver outcomes (satisfaction, physical and mental health status, burden, and benefits) were evaluated before and after program use. Caregivers reported significant improvements in mental health post-program. Caregivers who provided care to individuals with impaired physical health experienced meaningful improvements in burden after the support services were rendered. Supporting caregiver health status through such programs is vital to preserve noninstitutional long-term care for persons aging with disabilities, particularly when care is provided over many years to an individual with physical impairments. PMID- 22324333 TI - Growing health disparities for persons who are aging with intellectual and developmental disabilities: the social work linchpin. AB - Similar to the general population, adults with intellectual and developmental disabilities (IDD) are living into their 70s and beyond. Health care disparities have been well-documented for this vulnerable and underserved population. Social workers are often responsible for assessment, coordination of care, and negotiation of needed services for people with IDD. This article explores the challenges facing social workers in meeting the growing health and social needs of aging adults with IDD and their families. Trends in social work practice and gaps in education are discussed as they relate to addressing and reducing current health disparities. PMID- 22324334 TI - Improving health care delivery to aging adults with disabilities: social work with dual eligibles in a climate of health care reform. AB - Adults aging with disabilities comprise a diverse group. In this article, we identify the prevalence and characteristics of this target population, focusing on adults who are dually eligible for Medicare and Medicaid. We articulate challenges in the delivery of health, social, and support services to adults aging with disabilities, particularly how existing health care policy and financing contributes to fragmentation of care. Finally, we identify opportunities for social workers to advocate for and promote system improvements in the delivery of care for aging adults with disabilities in the current climate of health care reform. PMID- 22324336 TI - Content uniformity testing: suitability of different approaches for marketed low dose tablets. AB - CONTEXT: Content uniformity (CU) testing was developed and improved to control the effectiveness and safety of dosage units. Many modifications of compendial CU test have been introduced and several alternatives have been suggested. OBJECTIVES: This study aims to evaluate the degree of suitability of current USP CU test for low dose tablets and to compare the performance of the current test with that of the former USP27-NF22 and other alternatives for different sample sizes. METHODS: All locally marketed risperidone (RSP) tablets were analyzed using newly developed and validated isocratic UPLC method. The CU results were statistically analyzed in groups with sample sizes comparable to the USP sampling plans. RESULTS: Seven out of eleven products failed the different requirements of the former and current USP <905>chapters as well as of several alternative CU tests with several substantial deviations. CONCLUSION: The current USP <905> chapter was found to have some deficiencies that allowed such failed products to exist in the market. The dependence of compendial CU test on two-staged sampling plan and the use of arithmetic mean to calculate the reference and acceptance values were obvious shortcomings. PMID- 22324337 TI - Visualizing local doping effects of individual water clusters on gold(111) supported graphene. AB - The local charge carrier density of graphene can exhibit significant and highly localized variations that arise from the interaction between graphene and the local environment, such as adsorbed water, or a supporting substrate. However, it has been difficult to correlate such spatial variations with individual impurity sites. By trapping (under graphene) nanometer-sized water clusters on the atomically well-defined Au(111) substrate, we utilize scanning tunneling microscopy and spectroscopy to characterize the local doping influence of individual water clusters on graphene. We find that water clusters, predominantly nucleated at the atomic steps of Au(111), induce strong and highly localized electron doping in graphene. A positive correlation is observed between the water cluster size and the local doping level, in support of the recently proposed electrostatic-field-mediated doping mechanism. Our findings quantitatively demonstrate the importance of substrate-adsorbed water on the electronic properties of graphene. PMID- 22324338 TI - Selective synthesis of fullerenol derivatives with terminal alkyne and crown ether addends. AB - A series of isomerically pure alkynyl-substituted fullerenol derivatives such as C(60)(OH)(6)(O(CH(2))(3)CCH)(2) were synthesized through Lewis acid catalyzed epoxy ring opening and/or S(N)1 replacement reactions starting from the fullerene mixed peroxide C(60)(O)(t-BuOO)(4). Copper-catalyzed azide-alkyne cycloaddition readily converted the terminal alkynyl groups into triazole groups. Intramolecular oxidative alkyne coupling afforded a fullerenyl crown ether derivative. PMID- 22324339 TI - Femtosecond to second studies of a water-soluble porphyrin derivative in chemical and biological nanocavities. AB - The interactions of 5,10,15,20-tetrakis(4-sulfonatophenyl)-porphyrin (TSPP) with a quaternary ammonium modified beta-cyclodextrin (QA-beta-CD) and human serum albumin (HSA) protein in aqueous solutions at pH 7 were studied using steady state, stopped-flow, and femtosecond to millisecond spectroscopy. TSPP forms 1:1 and 1:2 complexes with QA-beta-CD (K(1) = 1.9 * 10(5) M(-1) and K(2) = 7 * 10(3) M(-1)) at 293 K, whereas with the HSA protein only 1:1 complex (K(1) = 1.7 * 10(6) M(-1)) has been found. The chemical and biological nanocavities have notable effects on the fluorescence lifetimes of the Q(x) state (from 9.3 to 11.1 ns in QA-beta-CD and 11.6 ns in HSA). Furthermore, the rotational times (400 ps for the free TSPP, 1.6 and 19 ns for QA-beta-CD and HSA protein complexes, respectively) clearly indicate the robustness of the formed entities. The confined environment does not affect much the fs dynamics (0.1-0.2 ps) of the encapsulated molecule. However, it clearly affect the ps one (1-2 ps (H(2)O) and 5-10 ps (QA-beta-CD and HSA)). The effect of O(2) on the relaxation of the triplet state of the free and encapsulated TSPP is also studied and the obtained results are discussed in light of the shielding effect provided by the chemical and biological cavities. The observed difference, longer triplet lifetime upon encapsulation, might be relevant to the efficiency of this porphyrin in photodynamic therapy. The presteady-state kinetics of the TSPP:HSA has been studied by the stopped-flow spectrometer, and a two-step model was proposed for the complexation processes. The results show the importance of the initial association step for the overall ligand recognition process. This first step occurs with rate constant of ~4 * 10(5) M(-1) s(-1), which is about 5 orders of magnitude larger than the rate constant of the consecutive relaxation processes. We believe that our observations of molecular interaction between TSPP, QA-beta CD, and HSA protein from femtosecond to second at both ground and electronically first excited state give detailed information to improve our understanding of this kind of system and thus for a better design of drug delivery nanocarriers. PMID- 22324340 TI - Proton transfer step in the carbon dioxide capture by monoethanol amine: a theoretical study at the molecular level. AB - An aqueous solution of monoethanol amine (MEA) has been utilized in an industrial process of CO(2) absorption. The chemical reaction between CO(2) and MEA, which is employed in the process, consists of two steps. After the formation of the MEA CO(2) complex ("capture"), a proton transfers from the complex to give a final product. In the present study, the overall mechanism of the reaction is discussed, especially focusing on the proton transfer step. Using RISM-SCF-SEDD, a hybrid method of electronic structure theory and statistical mechanics for molecular liquid, we clarified that the role of MEA as a base is crucial in the proton transfer step. PMID- 22324341 TI - Long-range electron transport of ruthenium-centered multilayer films via a stepping-stone mechanism. AB - We studied electron transport of Ru complex multilayer films, whose structure resembles redox-active complex films known in the literature to have long-range electron transport abilities. Hydrogen bond formation in terms of pH control was used to induce spontaneous growth of a Ru complex multilayer. We made a cross check between electrochemical measurements and I-V measurements using PEDOT:PSS to eliminate the risk of pinhole contributions to the mechanism and have found small beta values of 0.012-0.021 A(-1). Our Ru complex layers exhibit long-range electron transport but with low conductance. On the basis of the results of our theoretical-experimental collaboration, we propose a modified tunneling mechanism named the "stepping-stone mechanism", where the alignment of site potentials forms a narrow band around E(F), making resonant tunneling possible. Our observations may support Tuccito et al.'s proposed mechanism. PMID- 22324342 TI - Natural outbreak of Streptococcus agalactiae (GBS) infection in wild giant Queensland grouper, Epinephelus lanceolatus (Bloch), and other wild fish in northern Queensland, Australia. AB - Ninety-three giant Queensland grouper, Epinephelus lanceolatus (Bloch), were found dead in Queensland, Australia, from 2007 to 2011. Most dead fish occurred in northern Queensland, with a peak of mortalities in Cairns in June 2008. In 2009, sick wild fish including giant sea catfish, Arius thalassinus (Ruppell), and javelin grunter, Pomadasys kaakan (Cuvier), also occurred in Cairns. In 2009 and 2010, two disease epizootics involving wild stingrays occurred at Sea World marine aquarium. Necropsy, histopathology, bacteriology and PCR determined that the cause of deaths of 12 giant Queensland grouper, three wild fish, six estuary rays, Dasyatis fluviorum (Ogilby), one mangrove whipray, Himantura granulata (Macleay), and one eastern shovelnose ray, Aptychotrema rostrata (Shaw), was Streptococcus agalactiae septicaemia. Biochemical testing of 34 S. agalactiae isolates from giant Queensland grouper, wild fish and stingrays showed all had identical biochemical profiles. The 16S rRNA gene sequences of isolates confirmed all isolates were S. agalactiae; genotyping of selected S. agalactiae isolates showed the isolates from giant Queensland grouper were serotype Ib, whereas isolates from wild fish and stingrays closely resembled serotype II. This is the first report of S. agalactiae from wild giant Queensland grouper and other wild tropical fish and stingray species in Queensland, Australia. PMID- 22324343 TI - Diversity of Flavobacterium psychrophilum and the potential use of its phages for protection against bacterial cold water disease in salmonids. AB - Flavobacterium psychrophilum causes rainbow trout fry syndrome (RTFS) and cold water disease (CWD) in salmonid aquaculture. We report characterization of F. psychrophilum strains and their bacteriophages isolated in Chilean salmonid aquaculture. Results suggest that under laboratory conditions phages can decrease mortality of salmonids from infection by their F. psychrophilum host strain. Twelve F. psychrophilum isolates were characterized, with DNA restriction patterns showing low diversity between strains despite their being obtained from different salmonid production sites and from different tissues. We isolated 15 bacteriophages able to infect some of the F. psychrophilum isolates and characterized six of them in detail. DNA genome sizes were close to 50 Kbp and corresponded to the Siphoviridae and Podoviridae families. One isolate, 6H, probably contains lipids as an essential virion component, based on its chloroform sensitivity and low buoyant density in CsCl. Each phage isolate rarely infected F. psychrophilum strains other than the strain used for its enrichment and isolation. Some bacteriophages could decrease mortality from intraperitoneal injection of its host strain when added together with the bacteria in a ratio of 10 plaque-forming units per colony-forming unit. While we recognize the artificial laboratory conditions used for these protection assays, this work is the first to demonstrate that phages might be able protect salmonids from RTFS or CWD. PMID- 22324344 TI - Oral DNA vaccination of rainbow trout, Oncorhynchus mykiss (Walbaum), against infectious haematopoietic necrosis virus using PLGA [Poly(D,L-Lactic-Co-Glycolic Acid)] nanoparticles. AB - A DNA vaccine against infectious haematopoietic necrosis virus (IHNV) is effective at protecting rainbow trout, Oncorhynchus mykiss, against disease, but intramuscular injection is required and makes the vaccine impractical for use in the freshwater rainbow trout farming industry. Poly (D,L-lactic-co-glycolic acid) (PLGA) is a U.S. Food and Drug Administration (FDA) approved polymer that can be used to deliver DNA vaccines. We evaluated the in vivo absorption of PLGA nanoparticles containing coumarin-6 when added to a fish food pellet. We demonstrated that rainbow trout will eat PLGA nanoparticle coated feed and that these nanoparticles can be detected in the epithelial cells of the lower intestine within 96 h after feeding. We also detected low levels of gene expression and anti-IHNV neutralizing antibodies when fish were fed or intubated with PLGA nanoparticles containing IHNV G gene plasmid. A virus challenge evaluation suggested a slight increase in survival at 6 weeks post-vaccination in fish that received a high dose of the oral vaccine, but there was no difference when additional fish were challenged at 10 weeks post-vaccination. The results of this study suggest that it is possible to induce an immune response using an orally delivered DNA vaccine, but the current system needs improvement. PMID- 22324345 TI - Differential expression profiling of orange-spotted grouper larvae, Epinephelus coioides (Hamilton), that survived a betanodavirus outbreak. AB - Nervous necrosis virus (NNV), a piscine nodavirus, has caused serious viral nervous necrosis and viral encephalopathy and retinopathy in hatchery-reared larvae and juveniles of a wide range of marine teleost species worldwide in the last two decades. Although the mortality of NNV-infected larvae is nearly 100%, there are still some larvae that survive this catastrophe. To comprehensively understand the variations of these survivors at the molecular level, we collected orange-spotted grouper larvae that survived an NNV outbreak in an indoor hatchery in southern Taiwan to study differential gene expression. Healthy larvae with high, medium and low levels of detected NNV were compared with morbid larvae using a 9600-clone-containing grouper larva cDNA microarray, and differential gene expression was further confirmed by a quantitative real-time polymerase chain reaction. Significant variation exists in healthy larvae. The following genes were upregulated: adenylate kinase 1-2, myosin binding protein H-like, myosin light chain 2, myosin light chain 3, tropomyosin, fast/white muscle troponin T embryonic isoform, and parvalbumin 1 and 2 genes. The following genes were downregulated: apolipoprotein A-I, trypsinogen, pyruvate kinase and astacin like metalloprotease. Moreover, immunoglobulin M heavy chain gene transcription was significantly higher in healthy larvae that had high virus levels, indicating that humoral immunity might protect organisms from viral infection. These results suggest that some non-immune-related genes may have played important roles in survival during the larval metamorphosis stage, after betanodavirus infection. PMID- 22324346 TI - Expression profiles of seven channel catfish antimicrobial peptides in response to Edwardsiella ictaluri infection. AB - Using quantitative polymerase chain reaction (QPCR), the relative transcriptional levels of seven channel catfish antimicrobial peptide (AMP) genes (NK-lysin type 1, NK-lysin type 2, NK-lysin type 3, bactericidal permeability-increasing protein, cathepsin D, hepcidin and liver-expressed AMP 2) in response to Edwardsiella ictaluri infection were determined. None of the AMP genes tested was significantly upregulated at 2 h post-infection. Hepcidin was the only one that was significantly (P<0.05) upregulated at 4, 6 and 12 h post-infection. At 24 and 48 h post-infection, four AMPs (hepcidin, NK-lysin type 1, NK-lysin type 3 and cathepsin D) were significantly (P<0.05) upregulated. Among all the AMPs that were significantly upregulated at different time points, hepcidin at 4, 6 and 12 h post-infection was upregulated the most. When catfish were injected with different doses of E. ictaluri, all lethal doses were able to induce significant (P <0.05) upregulation of hepcidin in the posterior kidney, whereas sublethal doses failed to induce any significant upregulation of hepcidin. In vitro growth studies revealed that the presence of synthetic hepcidin peptide at a concentration of 16 MUm or higher significantly inhibited the cell proliferation of E. ictaluri. Taken together, our results suggest that hepcidin might play an important role in the channel catfish defence against E. ictaluri infection. PMID- 22324347 TI - Spontaneous schwannoma in zebrafish, Danio rerio (Hamilton). PMID- 22324348 TI - Ammonium chloride bath treatment as a quarantine measure to prevent spread of Lernaea cyprinacea infection during transfer of fish from affected ponds. PMID- 22324349 TI - The effect of aspirin in transfusion-related acute lung injury in critically ill patients. AB - Aspirin has been found to improve outcomes in an animal model of transfusion related acute lung injury. We examined the association of aspirin use before admission to the intensive care unit and the development of transfusion-related acute lung injury in critically ill patients. We performed a post-hoc analysis of a nested case-control study that had been undertaken in a tertiary referral hospital. Transfusion-related acute lung injury cases were matched with controls (transfused patients not developing lung injury). Of these 218 patients, 66 used aspirin (30%). Use of aspirin did not alter the risk of transfusion-related acute lung injury after transfusion of platelets (OR 1.06, CI 0.59-1.91, p = 0.85), plasma (OR 1.06, 95% CI 0.59-1.92, p = 0.84), or red blood cells (OR 1.09, 95% CI 0.61-1.94, p = 0.77). Adjustment for confounding variables using propensity scoring also did not affect the risk of acquiring transfusion-related acute lung injury (p = 0.66). In conclusion, aspirin did not protect against transfusion related lung injury in this cohort of critically ill patients. PMID- 22324350 TI - Library synthesis and antibacterial investigation of cationic anthraquinone analogs. AB - We report the parallel synthesis of a series of novel 4,9-dioxo-4,9-dihydro-1H naphtho[2,3-d][1,2,3]triazol-3-ium chloride salts, which are analogs to cationic anthraquinones. Three synthetic protocols were examined leading to a convenient and facile library synthesis of the cationic anthraquinone analogs that contain double alkyl chains of various lengths (C(2)-C(12)) at N-1 and N-3 positions. The antibacterial activities of these compounds were evaluated against Gram-positive bacterium Staphylococcus aureus and Gram-negative bacterium Escherichia coli. The antibacterial activities of these compounds were expected to be associated with the structural features of naphthoquinone, cation and lypophilic alkyl chain and, interestingly, they showed much higher levels of antibacterial activities against G+ than G- bacteria. In addition, when the total number of carbon atoms of the alkyl groups at both N-1 and N-3 positions lies between 9 and 18, the bactericidal activity against S. aureus increased with increasing alkyl chain length at both N-atoms with MIC <= 1 MUg/mL. PMID- 22324351 TI - Mast cell leukemia: identification of a new c-Kit mutation, dup(501-502), and response to masitinib, a c-Kit tyrosine kinase inhibitor. AB - OBJECTIVE: Most patients with systemic mastocytosis bear mutations in the tyrosine kinase receptor gene c-Kit. Limited treatment options exist for mast cell leukemia, a rare form of systemic mastocytosis associated with a dire prognosis. Our aim was to investigate c-Kit mutations associated with mast cell leukemia and find new treatment for this severe form of mastocytosis. PATIENT AND METHODS: We describe here a patient with mast cell leukemia characterized by 42% of circulating mast cells associated with a previously unidentified c-Kit mutation in adult mastocytosis: dup(501-502). MAIN FINDINGS: This patient was treated with masitinib, a novel c-Kit tyrosine kinase inhibitor, with a dramatic response observed following 3 months of treatment, including clinical improvement, disappearance of circulating mast cells, and decrease in both serum histamine and tryptase levels. In vitro and ex vivo research was performed on the patient's cells and revealed constitutive c-Kit phosphorylation in mast cell leukemia. CONCLUSIONS: This case highlights the importance of sequencing all c Kit exons when the classical D816V c-Kit mutation is not found, even in adults with SM. It also indicates that masitinib may be safe and effective for the treatment for some mast cell leukemia. PMID- 22324352 TI - Detection and molecular identification of human adenoviruses and enteroviruses in wastewater from Morocco. AB - AIMS: Reclaimed wastewater is a considerable water resource in Morocco. Its agricultural reuse requires an assessment of viral contamination. The aim of this study was to detect both infectious and noninfectious human adenoviruses (HAdV) and enteroviruses (EV) in raw wastewater and treat effluent from wastewater treatment plants (WWTPs) and domestic sewage in Morocco. METHODS AND RESULTS: A total of 22 samples were analysed. A polyethylene glycol (PEG) precipitation method was used, followed by integrated cell culture-PCR (ICC-PCR) using two cell lines: human rhabdomyosarcoma tumour tissue and laryngeal carcinoma cells (RD and Hep2 cells). Furthermore, viral genome amplification was confirmed by sequencing. HAdV were detected in 10 (45.5%) of the 22 samples involving two species: HAdV-B and HAdV-D. EV was detected in 5 (23%) samples belonging to Coxsackievirus B5 and poliovirus vaccine strain (Sabin 2). CONCLUSIONS: Human adenoviruses and EV were detected in the analysed samples from two WWTPs and HAdV in domestic sewage. SIGNIFICANCE AND IMPACT OF THE STUDY: This work is the first study in Morocco using cell culture, PCR and sequencing of enteric viruses from wastewater. The presence of infectious HAdV and EV in treated effluent emphasizes the need of wastewater treatment surveillance. PMID- 22324353 TI - Comparative analysis of spontaneous and mycobacterial antigen-induced secretion of Th1, Th2 and pro-inflammatory cytokines by peripheral blood mononuclear cells of tuberculosis patients. AB - The cytokines produced by T helper (Th)1 cells (IFN-gamma, IL-2 and TNF-beta) correlate with protection, whereas the cytokines released by Th2 cells (IL-4, IL 5) and the anti-inflammatory cytokine IL-10 correlate with pathogenesis of tuberculosis (TB). However, the pro-inflammatory cytokines (IL-1beta, IL-6, IL-8, TNF-alpha and IL-12p70) are responsible for both protection and pathogenesis of TB. The aim of this work was to carry out a comparative analysis of cytokines present in early (day 2) and late (day 6) cultures of peripheral blood mononuclear cells (PBMCs) obtained from pulmonary tuberculosis patients. PBMCs were cultured in vitro in the absence and presence of exogenously added complex mycobacterial antigens and RD1 peptide pool. The supernatants were collected on day 2 and day 6 of culture and assayed for secreted cytokines using the flow cytomix assay. All of the cytokines, except for IL-12p70, were spontaneously secreted by PBMCs of 27-100% TB patients, but only TNF-alpha concentration was significantly higher on day 2 than day 6 (P < 0.05). Two days following antigenic stimulation, only IL-1beta, IL-6, TNF-alpha and IL-10 were secreted in response to some mycobacterial antigens. However, 6 days later, all of the cytokines, except for IL-2, IL-4, IL-5 and IL-8, were secreted significantly in response to all complex antigens and RD1 peptides, compared with the non-stimulated cultures (P < 0.05). In conclusion, the study shows that the longer in vitro stimulation time (6 days) was necessary for the optimal induction of IFN-gamma and TNF-beta, and practically convenient for the detection of IL-10, IL-1 beta, TNF-alpha and IL-6. PMID- 22324354 TI - Obatoclax mesylate : pharmacology and potential for therapy of hematological neoplasms. AB - INTRODUCTION: Augmentation and acceleration of apoptosis for cancer therapy are logical therapeutic strategies given the increasing body of data suggesting the dysregulation of control of cell death in many neoplasms. Apoptosis is particularly well studied in hematological neoplasms, thus these varied diseases present opportunities for pro-apoptotic drug development both as single agents and in combination with established therapies. Accordingly, several agents targeting function of anti-apoptotic Bcl-2 family members have entered clinical trials in the last decade and are discussed. AREAS COVERED: The pan Bcl-2 family member BH3 domain mimetic obatoclax (GX15-070) is currently under clinical evaluation in solid tumors and hematological neoplasms. This agent offers the attractive property of uniformly inhibiting all of the anti-apoptotic members of the Bcl-2 protein family. Its chemistry and preclinical development and activity are reviewed. Pharmacology, pharmacodynamics, drug resistance and clinical use of this agent in leukemias and lymphomas are discussed. The prospects for obatoclax in changing clinical practice are addressed. EXPERT OPINION: Obatoclax may not prove to have dramatic single agent activity for hematological neoplasms. It seems more likely that its activity will be manifest in combination therapy with other agents, particularly cytotoxic chemotherapies. Results of ongoing studies are awaited. PMID- 22324355 TI - Associations between health-related quality of life and financial barriers to care among women veterans and women non-veterans. AB - The authors of this study examined the association between health-related quality of life and financial barriers to care, defined as not getting the needed care due to cost considerations. To better understand health-related quality of life among women veterans, the authors compared women veterans to women non-veterans. The authors conducted cross-sectional analyses using data from the 2009 Behavioral Risk Factor Surveillance System survey. The authors assessed four health-related quality of life measures: (1) general health; (2) physical health; (3) mental health; and (4) functional status. The authors performed multinomial logistic regressions to examine the relationship between financial barriers to receiving healthcare and health-related quality of life measures after controlling for other independent variables. The authors included women veterans not in active military duty (N = 3,747) and a matched sample of women non veterans (N = 3,747), selected using a propensity score method so that they would have distributions of demographic and socioeconomic characteristics similar to those of the veterans. Overall, 14% of women reported financial barriers. Women who reported financial barriers to receiving healthcare were more likely to have poor health-related quality of life in all four dimensions than those who did not report such barriers. Compared to women non-veterans, women veterans did not differ in reported financial barriers but were more likely to report poor health related quality of life. Reporting financial barriers to receiving needed healthcare was significantly associated with poor health-related quality of life among women. Veteran status was also significantly associated with poor health related quality of life. These findings suggest the need for healthcare policy makers and practitioners to align emerging new models of healthcare delivery to improve health-related quality of life for women veterans. PMID- 22324356 TI - Development of a shorter version of the osteoporosis knowledge assessment tool. AB - The aim of the authors of this study was to develop a short version of the Osteoporosis Knowledge Assessment Tool to be used for the target population of young adult Serbian females as an easily implemented add-on questionnaire. The 20 item Osteoporosis Knowledge Assessment Tool was translated and culturally adapted using the Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes Measures. The validation study was conducted on a sample of 250 female students studying at the Faculty of Pharmacy at the University of Belgrade, during a two-month period (November-December 2010). The difficulty index, item-total correlations, and internal consistency were calculated first. Afterward, confirmatory factor analysis was applied to test the structure of the Osteoporosis Knowledge Assessment Tool models and develop a short version. The mean total Osteoporosis Knowledge Assessment Tool score was 8.31 (possible range 0-20). The confirmatory factor analysis fit indices indicated poor fit of the data to the originally hypothesized structure. The confirmatory factor analysis fit indices, difficulty indices, and content validity allowed trimming of the original model and development of a short version with nine items. The average chi-square value for the Osteoporosis Knowledge Assessment Tool short version was 31.79 (p = 0.240, SE = 0.176) with Bollen-Stine bootstrap p = 0.249, Tucker-Lewis Index = 0.925, Comparative Fit Index = 0.944 and Root Mean Square Error of Approximation = 0.027. The Osteoporosis Knowledge Assessment Tool thus had acceptable characteristics and may be used for osteoporosis knowledge assessment. PMID- 22324357 TI - Smoking cessation programs targeted to women: a systematic review. AB - The authors of this systematic review aimed to examine tobacco interventions developed to meet the needs of women, to identify sex- and gender-specific components, and to evaluate their effects on smoking cessation in women. The authors searched electronic databases in the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, EBSCO, PsychINFO, CINHAL, and EMBASE; the search was not restricted by publication date. Data was extracted from published peer-reviewed articles on participants, setting, treatment models, interventions, length of follow-up, and outcomes. The main outcome variable was abstinence from smoking. A total of 39 studies were identified. In efficacy studies, therapists addressed weight concerns and non-pharmacological aspects of smoking, taught mood/stress management strategies, and scheduled the quit date to be timed to the menstrual cycle. In effectiveness studies, therapists were peer counselors, provided telephone counseling, and/or distributed gendered booklets, videos, and posters. Among efficacy studies, interventions addressing weight gain/concerns showed the most promising results. If medication can support smoking cessation in women and how it interacts with non-pharmacological treatment also warrant further research. For effectiveness studies, the available evidence suggests that smoking should be addressed in low-income women accessing public health clinics. Further attention should be devoted to identifying new settings for providing smoking cessation interventions to women from disadvantaged groups. Women specific tobacco programs help women stop smoking, although they appear to produce similar abstinence rates as non-sex/gender specific programs. Offering interventions for women specifically may reduce barriers to treatment entry and better meet individual preferences of smokers. Developing approaches that fully account for the multiple challenges treatment-seeking women face is still an area of research. PMID- 22324358 TI - Promoting use of nutrition and physical activity community resources among women in a family planning clinic setting. AB - Research increasingly supports promotion of nutrition and physical activity community resources to support individual-level health promotion interventions. However, even when such resources exist, they are often not well used. In this article, the authors describe the results of formative research regarding patient and health promotion professionals' perspectives on methods to encourage use of community resources among patients accessing family planning services at a local health department in eastern North Carolina. In March through May of 2010, the authors conducted qualitative in-depth interviews with 30 female patients, aged 18-44 years, and five local key informants. Interviews were transcribed verbatim, imported into Atlas Ti for data management, and independently double-coded. Free, easily accessible, and family-friendly resources were most appealing to participants. Key informants offered creative ideas for promoting the use of resources, such as parks and farmers' markets, and included integration of such resources into health care provider prescriptions and taking group trips to resources. Results of this study can guide similar programs attempting to promote the use of resources among hard-to-reach groups. PMID- 22324359 TI - Sexual minority status and long-term breast cancer survivorship. AB - Sexual minority women, such as lesbians, bisexuals, and women who have a woman partner face unique challenges, such as deciding on disclosing their sexual minority status to health providers. The purpose of this qualitative study was to explore the perceptions of sexual minority women who were long-term breast cancer survivors. Twenty-two sexual minority women, diagnosed with non-metastatic breast cancer between 2000 and 2005, participated in semi-structured, open-ended interviews. Interviews were audio-recorded, transcribed, and analyzed to identify emergent themes to summarize sexual minority women's perceptions of breast cancer survivorship. Participants' perceptions about the impact of their sexual minority identity on breast cancer survivorship consisted of: (1) breast cancer is a women's issue, not a lesbian issue; (2) I can manage my identity in the context of breast cancer; and (3) I am better off than heterosexual women. The authors' findings suggest a possible disconnect between sexual minority women with breast cancer who de-emphasized the importance of sexual minority status and the research community that emphasizes the importance of this status. Prior to counting on sexual minority women's interest in studies, researchers may need to educate sexual minority women about the need of breast cancer studies. PMID- 22324360 TI - Addressing the silence in the noise: how abortion support talklines meet some women's needs for non-political discussion of their experiences. AB - Abortion is a frequent topic in political discourse, but few opportunities are available for women to discuss their complex emotions and experiences concerning abortion. Popular belief holds that many women need "counseling" about their decision to have an abortion, but little systematic after-abortion emotional care is available. The authors of this study conducted semi-structured interviews (N = 7) and focus groups (N = 2; 13 participants) with staff members and volunteer counselors at four abortion support talklines between February 2009 and March 2010 for their insights into the post-abortion needs of callers. The authors found evidence that some women needed a space devoid of politics for processing their experience and emotions over time. Talklines begin to meet these needs, especially the episodic processing needs of women experiencing emotional difficulty at any time after an abortion. However, some mental health needs are still unmet, including those among women experiencing emotional difficulty due to preexisting conditions co-occurring with, but not caused by, the abortion. The authors of this study call for integrating after-abortion emotional support more fully into the work of abortion provision and women's mental health advocates. The authors warn against using these findings to support legal mandates for post abortion support, highlighting the negative consequences of such mandates in the pre-abortion arena. PMID- 22324361 TI - Long-term selective retention of natural Cs and Rb by highly weathered coastal plain soils. AB - Naturally occurring Cs and Rb are distinctly more abundant relative to K in the highly weathered upland soils of the Savannah River Site, South Carolina, than in average rock of Earth's upper continental crust (UCC), by factors of 10 and 4, respectively. Naturally occurring Cs has been selectively retained during soil evolution, and Rb to a lesser extent, while K has been leached away. In acid extracts of the soils, the Cs/K ratio is about 50 times and the Rb/K ratio about 15 times the corresponding ratios for the UCC, indicating that relatively large amounts of natural Cs and Rb have been sequestered in soil microenvironments that are highly selective for these elements relative to K. Cation exchange favoring Cs and Rb ions, and subsequent fixation of the ions, at sites in interlayer wedge zones within hydroxy-interlayered vermiculite particles may account for the observations. The amounts of stable Cs retained and the inferred duration of the soil evolution, many thousands of years, provide new insights regarding long-term stewardship of radiocesium in waste repositories and contaminated environments. Study of natural Cs in soil adds a long-term perspective on Cs transport in soils not available from studies of radiocesium. PMID- 22324362 TI - In situ gelling properties of anionic thiomers. AB - The aim of this study was to investigate in situ crosslinking systems of anionic thiolated polymers. In order to accelerate the increase in dynamic viscosity of thiolated polymers (thiomers), they were combined with hydrogen peroxide, carbamide peroxide and ammonium persulfate. Thiomers (pectin-cysteine (Pec-Cys), sodium carboxymethylcellulose-cysteine (NaCMC-Cys) and poly(acrylic acid) cysteine (PAA-Cys)) were synthesized via amide bond formation between the carboxylic acid group of polymers and the primary amino group of l-cysteine. The rheological properties of 1% (m/v) thiomer solutions with oxidizing agents were compared by oscillatory measurements over time (120 min). Pec-Cys and NaCMC-Cys with hydrogen and carbamide peroxide showed a sol-gel phase transition within a few minutes and scored up to 13,000-fold increase in dynamic viscosity. Furthermore, only thiomers exhibiting a polysaccharide backbone (Pec-Cys and NaCMC-Cys) showed a significant increase in viscosity (p < 0.05). In contrast, measurements of carbohydrate thiomers in combination with ammonium persulfate showed an initial increase in viscosity. Afterwards, a decrease in viscosity was observed likely caused by chain scission. According to these results, carbohydrate thiomer/oxidizing agent systems might be useful for various pharmaceutical applications such as for in situ gelling liquid/semisolid formulations or in tissue engineering. PMID- 22324363 TI - Block copolymer micelles with pendant bifunctional chelator for platinum drugs: effect of spacer length on the viability of tumor cells. AB - Three monomers with 1,3-dicarboxylate functional groups but varying spacer lengths were synthesized via carbon Michael addition using malonate esters and ethylene- (MAETC), butylene- (MABTC), and hexylene (MAHTC) glycol dimethacrylate, respectively. Poly[oligo-(ethylene glycol) methylether methacrylate] (POEGMEMA) was prepared in the presence of a RAFT (reversible addition-fragmentation chain transfer) agent, followed by chain extension with the prepared monomers to generate three different block copolymers (BP-E80, BP-B82, and BP-H79) with similar numbers of repeating units, but various spacer lengths as distinguishing features. Conjugation with platinum drugs created macromolecular platinum drugs resembling carboplatin. The amphiphilic natures of these Pt-containing block copolymers led to the formation micelles in solution. The rate of drug release of all micelles was similar, but a noticeable difference was the increasing stability of the micelle against dissociation with increasing spacer length. The platinum conjugated polymer showed high activity against A549, OVCAR3, and SKOV3 cancer cell lines exceeding the activity of carboplatin, but only the micelle based on the longest spacer had IC(50) values as low as cisplatin. Cellular uptake studies identified a better micelle uptake with increasing micelle stability as a possible reason for lower IC(50) values. The clonogenic assay revealed that micelles loaded with platinum drugs, in contrast to low molecular weight carboplatin, have not only better activity within the frame of a 72 h cell viability study, but also display a longer lasting effect by preventing the colony formation A549 for more than 10 days. PMID- 22324365 TI - Species-specific identification of seven vegetable oils based on suspension bead array. AB - Species adulteration of vegetable oils has become a main form of adulteration in vegetable oils, severely violating consumer rights and causing disorder in the market. A reliable method of species authentication of vegetable oils is desirable. This paper reports a novel method for identification of seven species of vegetable oils based on suspension bead array. One pair of universal primers and seven species-specific probes were designed targeting rbcl gene of the chloroplast. Each probe was coupled to a unique color-coded microsphere. Biotinylated PCR amplicons of seven oils were hybridized to the complementary probes on microsphere sets. Bound amplicons were detected fluorometrically using a reporter dye, streptavidin-R-phycoeryt hrin (SA-PE). A sample could be analyzed less than 1 h after PCR amplification. With the exception of olive probe, all probes showed no cross-reactivity with other species. Absolute detection limit of the seven probes ranged from 0.01 ng/MUL to 0.0001 ng/MUL. Detection limit in DNA mixture was from 10% to 5%. Detection of vegetable oils validated the effectiveness of the method. The suspension bead array as a rapid, sensitive, and high-throughput technology has potential to identify more species of vegetable oils with increased species of probes. PMID- 22324366 TI - Solution-gated graphene field effect transistors integrated in microfluidic systems and used for flow velocity detection. AB - Solution-gated graphene field effect transistors (SGGT) were integrated in microfluidic systems. The transfer characteristics of a SGGT with an Ag/AgCl gate electrode shifted horizontally with the change of the ionic concentration of KCl solution in the microchannel and the relationship can be fitted with the Nernst equation, which was attributed to the change of the potential drop at the Ag/AgCl electrode. Therefore the gate electrode is one important factor for the ion sensitive property of the SGGT. Then SGGTs were used as flow velocity sensors, which were based on measuring the streaming potentials in microfluidic channels. A linear relationship between the shift of the transfer curve of the SGGT and the flow velocity was obtained, indicating that the SGGT is a promising transducer for measuring flow velocity in a microchip. Since the streaming potential is influenced by the three physical quantities, including the flow velocity, the ionic strength of the fluid and the zeta potential of the substrate, the device can be used for sensing any one of the three quantities when the other two were known. It is noteworthy that SGGTs have been used for various types of chemical and biological sensors. Array of the devices integrated in multichannel microchips are expected to find many important applications in the lab-on-a-chip systems in the future. PMID- 22324367 TI - Genome affinity and meiotic behaviour in trigenomic hybrids and their doubled allohexaploids between three cultivated Brassica allotetraploids and Brassica fruticulosa. AB - The wild species Brassica fruticulosa Cyr. (FF, 2n = 16) is closely related to the cultivated Brassica species.Through interspecific reciprocal crosses between B. fruticulosa and three cultivated Brassica allotetraploids (AABB, AACC,and BBCC where A = 10, B = 8, and C = 9), four trigenomic hybrids (F.AC, 2n = 27; F.AB, 2n = 26; F.BC, 2n = 25;BC.F, 2n = 25) were produced. By chromosome doubling of respective hybrids, three allohexaploids (FF.AACC, 2n = 54;FF.AABB, 2n = 52; BBCC.FF, 2n = 50) were synthesized. In pollen mother cells (PMCs) of the trigenomic hybrids, 1-2 autosyndetic bivalents were detected within A, B, and C genomes but only one within F genome; 1-3 allosyndetic bivalents between any two genomes were observed, and a closer relationship of F and B genomes than F and A genomes or F and C genomes was revealed. The all ohexaploids showed a generally low but different pollen fertilities. The chromosomes in PMCs were predominantly paired as bivalents but some univalents and multivalents at variable frequencies were observed.The bivalents of homologous pairing for each genome prevailed, but all osyndetic quadrivalents and hexavalents involving any two genomes were observed, together with autosyndetic quadrivalents for A, B, and C genomes but not the F genome.The nondiploidized cytological behaviour of these allohexaploids contributed to their low fertility. The relationships between the genome affinity and meiotic behavior in these allohexaploids were discussed. PMID- 22324368 TI - Surface molecular imprinting in layer-by-layer films on silica particles. AB - An improvement to molecular imprinting in polymers, where bulk systems often suffer from slow dynamics of release and uptake, is the formation of thin films with imprinting sites that are more rapid to access by guest molecules. Based on our previous development of surface molecular imprinting layer-by-layer (LbL) films (SMILbL), the present paper presents selective imprinted sites in a surface film on dispersed silica particles, thus designing a SMILbL system with maximized active area and in addition allowing studies with bulk techniques. The multilayer is designed to include the template during the LbL buildup and to form a cross linked network upon UV-irradiation for enhanced stability. A theophylline moiety is grafted to poly(acrylic acid) as the template, while a UV-sensitive diazo polycation cross-links the polymers after irradiation. Electrophoretic measurements prove the successful buildup of the multilayers by an alternating sign of the zeta potential. Template release is achieved by cleavage of the grafted template. The released amount of template is quantified in solution by (1)H NMR spectra and is in good agreement with the prediction from surface coverage calculations. Rebinding studies of template to the now empty imprinted binding sites show a high affinity for a theophylline derivative with a rebound amount on the order of the original template content. In contrast to theophylline, caffeine with a very similar chemical structure-only differing in one functional group-shows very different binding properties due to a thiol moiety in the binding site. Thus, a particle system with very selective molecular imprinting sites is demonstrated. PMID- 22324369 TI - Does prohibitin expression regulate sperm mitochondrial membrane potential, sperm motility, and male fertility? AB - Prohibitin (PHB) is a highly conserved major sperm mitochondrial membrane protein whose absence in somatic cells is associated with mitochondrial membrane depolarization and increased generation of reactive oxygen species (ROS). Our recent findings suggest that high levels of oxidants in human semen may contribute to male infertility and that sperm motility could be the earliest and most sensitive indicator of oxidative damage. Based on PHB's roles in mitochondrial sub-compartmentalization and respiratory chain assembly, we examine sperm PHB expression and mitochondrial membrane potential (MITO) in infertile men with poor sperm motility (asthenospermia, A) and/or low sperm concentrations (oligoasthenospermia, OA). Here, we demonstrate that MITO is significantly lower in sperm from A and OA subjects than in normospermic (N) subjects; the decrease is more severe for OA than for A subjects. PHB expression is also significantly lower in sperm from A and OA subjects. Significantly positive correlations are found among PHB expression, MITO, and sperm motility in normospermic, asthenospermic, and oligoasthenospermic subjects. Collectively, our observations lead to the hypothesis that PHB expression is an indicator of sperm quality in infertile men, and that it regulates sperm motility via an alteration in MITO and increased ROS levels. PMID- 22324370 TI - Studies into the mechanism of CO-induced N2 cleavage promoted by an ansa hafnocene complex and C-C bond formation from an observed intermediate. AB - Carbonylation of the hafnocene dinitrogen complex, [Me(2)Si(eta(5) C(5)Me(4))(eta(5)-C(5)H(3)-(t)Bu)Hf](2)(MU(2), eta(2), eta(2)-N(2)), yields the corresponding hafnocene oxamidide compound, arising from N(2) cleavage with concomitant C-C and C-N bond formation. Monitoring the addition of 4 atm of CO by NMR spectroscopy allowed observation of an intermediate hafnocene complex with terminal and bridging isocyanates and a terminal carbonyl. (13)C labeling studies revealed that the carbonyl is the most substitutionally labile ligand in the intermediate and that N-C bond formation in the bridging isocyanate is reversible. No exchange was observed with the terminal isocyanate. Kinetic data established that the conversion of the intermediate to the hafnocene oxamidide was not appreciably inhibited by carbon monoxide and support a pathway involving rate-determining C-C coupling of the isocyanate ligands. Addition of methyl iodide to the intermediate hafnocene resulted in additional carbon-carbon bond formation arising from CO homologation following nitrogen methylation. Similar reactivity with (t)BuNCO was observed where C-C coupling occurred upon cycloaddition of the heterocumulene. By contrast, treatment of the intermediate hafnocene with CO(2) resulted in formation of a MU-oxo hafnocene with two terminal isocyanate ligands. PMID- 22324371 TI - Drug silica nanocomposite: preparation, characterization and skin permeation studies. AB - The aim of this work was to evaluate silica nanocomposites as topical drug delivery systems for the model drug, caffeine. Preparation, characterization, and skin permeation properties of caffeine-silica nanocomposites are described. Caffeine was loaded into the nanocomposites by grinding the drug with mesoporous silica in a ball mill up to 10 h and the efficiency of the process was studied by XRPD. Formulations were characterized by several methods that include FTIR, XRPD, SEM and TEM. The successful loading of caffeine was demonstrated by XRPD and FTIR. Morphology was studied by SEM that showed particle size reduction while TEM demonstrated formation of both core-shell and multilayered caffeine-silica structures. Solid-state NMR spectra excluded chemical interactions between caffeine and silica matrix, thus confirming that no solid state reactions occurred during the grinding process. Influence of drug inclusion in silica nanocomposite on the in vitro caffeine diffusion into and through the skin was investigated in comparison with a caffeine gel formulation (reference), using newborn pig skin and vertical Franz diffusion cells. Results from the in vitro skin permeation experiments showed that inclusion into the nanocomposite reduced and delayed caffeine permeation from the silica nanocomposite in comparison with the reference, independently from the amount of the tested formulation. PMID- 22324372 TI - Bacterial host interaction of GFP-labelled Vibrio anguillarum HI-610 with gnotobiotic sea bass, Dicentrarchus labrax (L.), larvae. AB - The location and cell damage caused by Vibrio anguillarum, the causative agent of classical vibriosis, within the developing gut of the newly hatched sea bass, Dicentrarchus labrax (L.), is unknown. A gnotobiotic sea bass model was used to investigate the early interactions of V. anguillarum with sea bass larvae. In the present study, germ-free sea bass larvae were orally exposed to a V. anguillarum HI-610 pathogen labelled with the green fluorescent protein (GFP-HI-610) and sampled at regular intervals. Pathogenic colonization of gut enterocytes was observed 2 h post-exposure (p.e.) and onwards, whereas bacteria within the swim bladder were visualized 48 h p.e and onwards. Ultrastructural findings demonstrated direct bacterial contact with the host cell in the oesophageal mucosa and putative attachment to microvilli of mid- and hindgut enterocytes. The present findings form a starting point for studies assessing the impact of potential candidates (probiotics, prebiotics, antimicrobial peptides) to mitigate bacterial virulence. PMID- 22324373 TI - Long-term management of acquired thrombotic thrombocytopenic purpura using serial plasma ADAMTS13 measurements. AB - Although significant advances in the understanding of TTP pathophysiology have been made in the last 15 yr, none have yet impacted the empiric treatment paradigm for this disease for which plasmapheresis is the mainstay. Laboratory assays for ADAMTS13 activity and inhibitors can be used to confirm a clinical diagnosis, but the assays are not routinely used to guide treatment. The routine availability of ADAMTS13 testing has allowed our group to tailor plasmapheresis and immunosuppressive therapy in patients under active treatment for TTP. In addition, the concept of establishing immune tolerance, similar to the eradication of a factor VIII inhibitor in patients with congenital or acquired hemophilia, has emerged as an important strategy to prevent early relapse of TTP. With the expected incorporation of recombinant ADAMTS13 into the treatment algorithm over the next several years, we anticipate that readily available ADAMTS13 testing will play an important role in individualized therapy that incorporates enzyme replacement and establishment of immune tolerance. PMID- 22324374 TI - A novel function for the haemopoietic supportive murine bone marrow MS-5 mesenchymal stromal cell line in promoting human vasculogenesis and angiogenesis. AB - The bone marrow contains specific microenvironmental stem cell niches that maintain haemopoiesis. CXCL12-expressing mesenchymal stromal cells are closely associated with the bone marrow sinusoidal endothelia, forming key elements of the haemopoietic stem cell niche, yet their ability to regulate endothelial function is not clearly defined. Given that the murine nestin(+) cell line, MS 5, provides a clonal surrogate bone marrow stromal niche capable of regulating both murine and human primitive haemopoietic stem/progenitor cell (HSC/HPC) fate in vitro, we hypothesized that MS-5 cells might also support new blood vessel formation and function. Here, for the first time, we demonstrate that this is indeed the case. Using proteome arrays, we identified HSC/HPC active angiogenic factors that are preferentially secreted by haemopoietic supportive nestin(+) MS 5 cells, including CXCL12 (SDF-1), NOV (CCN3), HGF, Angiopoietin-1 and CCL2 (MCP 1). Concentrating on CXCL12, we confirmed its presence in MS-5 conditioned media and demonstrated that its antagonist in receptor binding, AMD-3100, which mobilizes HSC/HPCs and endothelial progenitors from bone marrow, could significantly reduce MS-5 mediated human vasculogenesis in vitro, principally by regulating human endothelial cell migration. Thus, the clonal nestin(+) MS-5 murine bone marrow stromal cell line not only promotes human haemopoiesis but also induces human vasculogenesis, with CXCL12 playing important roles in both processes. PMID- 22324375 TI - Graphene-quantum-dot assembled nanotubes: a new platform for efficient Raman enhancement. AB - Graphene quantum dots (GQDs), single or few-layer graphenes with a size of only several nanometers, are a new type of quantum dots (QDs) with unique properties. The assembly of QDs in a geometrically well-defined fashion opens up opportunities to obtain access to the full potential of assembled QDs by virtue of the collective properties of the ensembles. In the current study, we present the well-organized assembly of zero-dimensional (0D) functional GQDs into 1D nanotube (NT) arrays and demonstrate their remarkable potential as a new metal free platform for efficient surface-enhanced Raman scattering (SERS) applications. The hierarchically porous 1D nanotube structure of 0D GQDs has been prepared by electrophoresis deposition within a nanoporous AAO template. On the basis of the unique porous nanotube architecture of GQDs, the GQD-NTs could ensure a more efficient charge transfer between the target molecules and the GQDs and thus produce much stronger SERS effect, exceeding that on flat graphene sheets. The unique architecture of 1D nanotubes of 0D GQDs provides a new point of view for designing and fabricating SERS substrates. PMID- 22324376 TI - Genogroup distribution of F-specific coliphages in wastewater and river water in the Kofu basin in Japan. AB - AIMS: To determine the genogroup distribution of F-specific coliphages in aquatic environments using the plaque isolation procedure combined with genogroup specific real-time PCR. METHODS AND RESULTS: Thirty water samples were collected from a wastewater treatment plant and a river in the Kofu basin in Japan on fine weather days. F-specific coliphages were detected in all tested samples, 187 (82%) of 227 phage plaques isolated were classified into one of the 4 F-specific RNA (F-RNA) coliphage genogroups and 24 (11%) plaques were F-specific DNA coliphages. Human genogroups II and III F-RNA coliphages were more abundant in raw sewage than animal genogroups I and IV, excluding one sample that was suspected to be heavily contaminated with sporadic heavy animal faeces. The secondary-treated sewage samples were highly contaminated with genogroup I F-RNA coliphages, probably because of different behaviours among the coliphage genogroups during wastewater treatment. The river water samples were expected to be mainly contaminated with human faeces, independent of rainfall effects. CONCLUSIONS: A wide range of F-specific coliphage genogroups were successfully identified in wastewater and river water samples. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results clearly show the usefulness of the genogroup-specific real time PCR for determining the genogroups of F-specific coliphages present in aquatic environments. PMID- 22324377 TI - Alveolar macrophage-derived vascular endothelial growth factor contributes to allergic airway inflammation in a mouse asthma model. AB - Vascular endothelial growth factor (VEGF) is a potent proangiogenic factor that correlates with vascular permeability and remodelling in asthma. Recently, alveolar macrophages (AM) were shown to be an important source of VEGF during lung injury. Our previous studies demonstrated that AM are an important subset of macrophages in the initiation of asthmatic symptoms. Here, we further investigated whether AM-derived VEGF was required for allergic airway inflammation in asthma. In this study, we reported that the expression of VEGF in AM was significantly increased after allergen challenge. Depleting AM or neutralizing VEGF in alveolus prevented ovalbumin (OVA)-induced asthma-related inflammation by inhibiting the infiltration of inflammatory cells in the lung, reduced the level of the cytokines, IL-4, IL-5, and IL-13, in the bronchoalveolar lavage fluid (BALF) and decreased airway hyperresponsiveness (AHR). Moreover, the inhibition of miR-20b increased the protein level of VEGF in normal AM; conversely, increasing miR-20b in asthmatic AM resulted in decreased VEGF protein levels. These findings suggest that AM-derived VEGF is necessary for allergic airway inflammation in asthmatic mice and miR-20b negatively regulates this expression. PMID- 22324378 TI - Geographic differences in perioperative opioid administration in children. AB - OBJECTIVES: To investigate whether geographic differences exist in perioperative opioid administration to children. AIM: To investigate whether perioperative fentanyl use for cleft lip and palate surgery varies between children of three different geographic regions. BACKGROUND: Differences have been found in perioperative opioid administration to children of differing ethnicity in the USA. Whether similar differences exist in perioperative opioid administration to children residing in different geographic regions is unknown. METHODS/MATERIALS: We retrospectively reviewed the medical records of ASA I children who underwent surgery under standardized general anesthesia between January 2010 and April 2011 during SMILE Network International mission trips to Africa, India and Central and South America. Perioperative administration of fentanyl was compared between these three locations. RESULTS: We analyzed data from 79 children who underwent surgery in Africa, 76 in India and 153 in Central and South America. Children in Central and South America were given <50% of the intraoperative amount of fentanyl (2.0 +/- 1.2 mcg.kg(-1) ) administered to children in Africa (4.1 +/- 2.4 mcg.kg(-1) ; P < 0.001) and children in India (4.3 +/- 2.2 mcg.kg(-1) ; P < 0.001). Postoperatively, fentanyl was administered in equivalent doses to all groups. CONCLUSIONS: Children in Central and South America received less opioid intraoperatively than African and Indian children, under standardized anesthesia for cleft surgeries. Further research is necessary to elucidate the mechanisms underlying these group differences. PMID- 22324379 TI - Species differences in the pharmacokinetics of KW-7158 [(2S)-(+)-3,3,3-Trifluoro 2-hydroxy-2-methyl-N-(5,5,10-trioxo-4,10-dihydrothieno[3,2-c][1]benzothiepin-9 yl)propanamide]: formation of hydrolyzed metabolite in human and animals. AB - Species differences in the pharmacokinetics of KW-7158 [(2S)-(+)-3,3,3-Trifluoro 2-hydroxy-2-methyl-N-(5,5,10-trioxo-4,10-dihydrothieno[3,2-c][1]benzothiepin-9 yl)propanamide] were studied in in vivo and in vitro experiments. The exposure ratio of hydrolyzed metabolite (M2, primary metabolite in human plasma)/KW-7158 was higher than the ratio of thiophen-to-furan converted metabolite (M1)/KW-7158 in human subjects after oral administration, but the mouse, rat and dog studies gave opposite results. M2 was produced in the highest amount by the 9000g supernatant of small intestine, followed by that of liver and kidney in human subjects. After correction for protein contents, the results obtained suggested that the small intestine plays a major role in the metabolism to M2 for the first pass effect after oral administration of KW-7158. The formation of M2 was independent of the presence of NADPH and was inhibited by various esterase inhibitors. These observations suggested that the predominant enzymes or isozymes involved in the formation of M2 are esterases, which differ between humans and animals. Such differences may be one of the reasons for the species differences in the pharmacokinetics of KW-7158 between humans and animals. PMID- 22324380 TI - Dora B. Goldstein 1922-2011. PMID- 22324381 TI - Mechanisms of action of selective serotonin reuptake inhibitors in Daphnia magna. AB - Selective serotonin reuptake inhibitors (SSRI) are known to increase offspring production in Daphnia magna. This study tested the hypothesis that the increase of serotonin postsynaptic activity by SSRI changes the perception of the food environment and switches life-history responses toward higher food level: females reproduced earlier, producing more but smaller offspring. D. magna reproduction tests, respiration, feeding, and survival-starvation assays and studies of lipids, proteins, and carbohydrate levels of unexposed and exposed females to the SSRI fluoxetine and fluvoxamine and the 5-HT serotonin receptor antagonist cyproheptadine were conducted. Factorial life-history experiments and reproductive assays showed that exposure to SSRI increased juvenile development rate, clutch size, and decrease offspring size at low and intermediate levels of food rations. These effects were reversed by the presence of cyproheptadine, indicating that 5-HT function was essential to the SSRI effects on Daphnia and linking them to the pharmacological effects of SSRI in humans. Respirometry and survival assays and biochemical analyses of lipids, proteins and carbohydrate levels showed that exposure to SSRI increased oxygen consumption rates and decreased carbohydrate levels in adult females. These changes did not affect survival under starving conditions, but they significantly affected the capacity of the exposed animals to survive under anoxic conditions. These results suggest that SSRI increased aerobic catabolism in D. magna making exposed individuals apparently more able to exploit food resources under normoxic conditions, but at the cost of being more sensitive to low oxygen levels, a common situation in natural environments. PMID- 22324382 TI - Strain-induced conductance modulation in graphene grain boundary. AB - Grain boundaries (GBs) are ubiquitous in polycrystalline graphene materials obtained by various growth methods. It has been shown previously that considerable electrical transport gap can be opened by grain boundaries. On the other hand, polycrystalline graphene with GBs is an atomically thin membrane that can sustain extraordinary amount of strain. Here, by using atomistic quantum transport numerical simulations, we examine modulation of electrical transport properties of graphene GBs. The results indicate the modulation of transport gap and electrical conductance strongly depends on the topological structure of the GB. The transport gap of certain GBs can be significantly widened by strain, which is useful for improving the on-off ratio in potential transistor applications and for applications as monolayer strain sensors. PMID- 22324383 TI - Does glycemic variability impact mood and quality of life? AB - BACKGROUND: Diabetes is a chronic condition that significantly impacts quality of life. Poor glycemic control is associated with more diabetes complications, depression, and worse quality of life. The impact of glycemic variability on mood and quality of life has not been studied. METHODS: A descriptive exploratory design was used. Twenty-three women with type 2 diabetes wore a continuous glucose monitoring system for 72 h and completed a series of questionnaires. Measurements included (1) glycemic control shown by glycated hemoglobin and 24-h mean glucose, (2) glycemic variability shown by 24-h SD of the glucose readings, continuous overall net glycemic action (CONGA), and Fourier statistical models to generate smoothed curves to assess rate of change defined as "energy," and (3) mood (depression, anxiety, anger) and quality of life by questionnaires. RESULTS: Women with diabetes and co-morbid depression had higher anxiety, more anger, and lower quality of life than those without depression. Certain glycemic variability measures were associated with mood and quality of life. The 24-h SD of the glucose readings and the CONGA measures were significantly associated with health related quality of life after adjusting for age and weight. Fourier models indicated that certain energy components were significantly associated with depression, trait anxiety, and overall quality of life. Finally, subjects with higher trait anxiety tended to have steeper glucose excursions. CONCLUSIONS: Data suggest that greater glycemic variability may be associated with lower quality of life and negative moods. Implications include replication of the study in a larger sample for the assessment of blood glucose fluctuations as they impact mood and quality of life. PMID- 22324384 TI - Dipeptidyl peptidase-4 inhibitors: 3 years of experience. AB - According to the latest American Diabetes Association guidelines, lowering glycated hemoglobin (HbA(1c)) to below or around 7% has been shown to reduce microvascular and neuropathic complications of diabetes and, if implemented soon after the diagnosis of diabetes, is associated with long-term reduction in macrovascular disease. Recently a new class of antidiabetes drugs has been developed, dipeptidyl peptidase-4 (DPP-4) inhibitors, which act by inhibiting DPP 4, the enzyme that inactivates glucagon-like peptide-1 (GLP-1). Through the inhibition of DPP-4, DPP-4 inhibitors enhance the effects of GLP-1 and glucose dependent insulinotropic peptide, increasing glucose-mediated insulin secretion and suppressing glucagon secretion. We conducted a review analyzing clinical efficacy and safety of DPP-4 inhibitors, both alone and in combination with other antidiabetes drugs, including randomized controlled trials about sitagliptin, vildagliptin, saxagliptin, and linagliptin conducted in the latest 15 years. We concluded that, once metformin fails to maintain glycemic control, addition of DPP-4 inhibitors should be the logical choice: they seems to lower HbA(1c) levels by 0.6-0.9 percentage points and to have a comparable effect on HbA(1c) versus the addition of a sulfonylurea or glitazone. They also have positive effects on beta-cell function, and they have neutral effects on body weight. Furthermore, DPP-4 inhibitors prevent the risk of hypoglycemia posed by sulfonylureas. PMID- 22324385 TI - Wound healing promoting activity of stem bark extract of Semecarpus anacardium using rats. AB - The wound healing promoting property of stem bark methanol extract of Semecarpus anacardium was evaluated at three different dosages by excision, incision and dead space wound models using Wistar albino rats. Framycetin skin ointment was used as standard. LD(50) of methanol extract was determined to be 500 mg kg(-1). In methanol extract (20% ointment) treated group, epithelialisation of the incision wound was faster with a high rate of wound contraction. The tensile strength of the incision wound was significantly increased when compared to other treated groups. The histological examination of the dead space wound model granulation tissue of the methanol extract (100 mg kg(-1)) treated group showed increased cross-linking of collagen fibres and absence of monocytes as compared to control. Methanol extract at 100 mg kg(-1) exhibited significant wound healing activity but was lesser than standard; whereas, in animals treated with 50 and 75 mg kg(-1) showed moderate activity. This investigation supported the ethnomedicinal claims of S. anacardium. PMID- 22324387 TI - What do we know about the relationship between source monitoring deficits and executive dysfunction? AB - In clinical neuropsychology, source monitoring deficits have been classically attributed to executive dysfunction. Nevertheless, in this review we identified only 16 papers that provided statistical data about the relationships between source monitoring and executive processes. Surprisingly, they reported either a total, partial or non-existent relationship between source monitoring and executive tasks. In order to understand and explain these contradictions, we classified the source and executive tasks of the 16 papers according to two well accepted definitions. Source tasks were classified using the Source Monitoring Framework (Johnson, Hashtroudi, & Lindsay, 1993 ) which specifies reality and external and internal source monitoring. Executive tasks were classified according to the model of Miyake Friedman, Emerson, Witzki, and Howerter (2000) which specifies complex, shifting, updating and inhibition tasks. We found that evaluation of reality and internal source monitoring was limited. Regarding executive functions, there was no assessment of updating and only a limited assessment of shifting and inhibition. Therefore, the relationship between source monitoring and executive functions remains an open question. Our findings point to the need for the simultaneous assessment of source monitoring and executive functions as defined by multidimensional theoretical frameworks. Such investigations would help in understanding the relationship between specific source monitoring deficits and specific executive decline in clinical populations. PMID- 22324388 TI - Different tests for a difference: how do we do research? PMID- 22324390 TI - Differential dynamic microscopy for anisotropic colloidal dynamics. AB - Differential dynamic microscopy (DDM) is a low-cost, high-throughput technique recently developed for characterizing the isotropic diffusion of spherical colloids using white-light optical microscopy. (1) We develop the theory for applying DDM to probe the dynamics of anisotropic colloidal samples such as various ordered phases, or particles interacting with an external field. The q dependent dynamics can be measured in any direction in the image plane. We demonstrate the method on a dilute aqueous dispersion of anisotropic magnetic particles (hematite) aligned in a magnetic field. The measured diffusion coefficients parallel and perpendicular to the field direction are in good agreement with theoretical values. We show how these measurements allow us to extract the orientational order parameter S(2) of the system. PMID- 22324389 TI - Review article: coeliac disease, new approaches to therapy. AB - BACKGROUND: Coeliac disease is managed by life-long gluten withdrawal from the diet. However, strict adherence to a gluten-free diet is difficult and is not always effective. Novel therapeutic approaches are needed to supplement or even replace the dietary treatment. AIM: To review recent advances in new therapeutic options for coeliac disease. METHODS: A literature search was performed on MEDLINE, EMBASE, Web of Science, Scopus, DDW.org and ClinicalTrials.gov for English articles and abstracts. The search terms used included, but not limited to, 'Celiac disease', 'new', 'novel', 'Advances', 'alternatives' and 'Drug therapy'. The cited articles were selected based on the relevancy to the review objective. RESULTS: Several new therapeutic approaches for coeliac disease are currently under development by targeting its underlying pathogenesis. Alternative therapies range from reproduction of harmless wheat strains to immunomodulatory approaches. Some of these therapies such as enzymatic cleavage of gluten and permeability inhibitors have shown promise in clinical studies. CONCLUSIONS: Gluten-free diet is still the only practical treatment for patients with coeliac disease. Novel strategies provide promise of alternative adjunctive approaches to diet restriction alone for patients with this disorder. PMID- 22324391 TI - Divergent functions of the myotubularin (MTM) homologs AtMTM1 and AtMTM2 in Arabidopsis thaliana: evolution of the plant MTM family. AB - Myotubularin and myotubularin-related proteins are evolutionarily conserved in eukaryotes. Defects in their function result in muscular dystrophy, neuronal diseases and leukemia in humans. In contrast to the animal lineage, where genes encoding both active and inactive myotubularins (phosphoinositide 3-phosphatases) have appeared and proliferated in the basal metazoan group, myotubularin genes are not found in the unicellular relatives of green plants. However, they are present in land plants encoding proteins highly similar to the active metazoan enzymes. Despite their remarkable structural conservation, plant and animal myotubularins have significantly diverged in their functions. While loss of myotubularin function causes severe disease phenotypes in humans it is not essential for the cellular homeostasis under normal conditions in Arabidopsis thaliana. Instead, myotubularin deficiency is associated with altered tolerance to dehydration stress. The two Arabidopsis genes AtMTM1 and AtMTM2 have originated from a segmental chromosomal duplication and encode catalytically active enzymes. However, only AtMTM1 is involved in elevating the cellular level of phosphatidylinositol 5-phosphate in response to dehydration stress, and the two myotubularins differentially affect the Arabidopsis dehydration stress responding transcriptome. AtMTM1 and AtMTM2 display different localization patterns in the cell, consistent with the idea that they associate with different membranes to perform specific functions. A single amino acid mutation in AtMTM2 (L250W) results in a dramatic loss of subcellular localization. Mutations in this region are linked to disease conditions in humans. PMID- 22324392 TI - Has Marlboro hijacked tobacco harm reduction? PMID- 22324393 TI - Dental practitioner concepts of efficiency related to the use of dental therapists. AB - OBJECTIVES: Efficiency is concerned with producing maximum output with the minimum input, although what constitutes inputs and outputs within an organization is not always clear. Labour substitution is one method of achieving efficiency gains, although cost savings are found to be context dependent and may not be achieved in some situations. Because dental therapists (DTs) in England are permitted to work in dental practices, we set out to investigate how efficiency with respect to the use of DTs is conceptualized by practitioners to deepen our understanding of the potential for substitution to realize efficiency gains in dental practice. METHODS: Nine dental practices were selected using a purposive sampling methodology to give a range of practice size and DT employment arrangements. Semi-structured interviews were held with 26 dentists. Transcripts were coded and analysed thematically. RESULTS: Efficiency was perceived as optimum use of surgery time to generate intermediate outputs of (i) managing patient flow to give patient satisfaction and business cash flow and (ii) volume of work (procedures and numbers of patients). DT efficiency gains were evaluated according to whether lower labour costs were offset by a slower working pace and higher rate of failed appointments. Patient need and demand, and whether the practice had health improvement goals, influenced whether DTs were deemed to improve efficiency. CONCLUSIONS: Findings are in accord with skill mix reviews in wider health care that substitution may be effective in improving efficiency but this may be limited to particular situations where conditions are conducive. More studies are needed to explore these issues further in other dental practice contexts and with other groups of dental auxiliary. PMID- 22324394 TI - An investigation of the versatile antioxidant mechanisms of action of rosmarinate alkyl esters in oil-in-water emulsions. AB - The antioxidant polar paradox postulates that nonpolar antioxidants are more effective in oil-in-water emulsions than polar antioxidants. However, this trend is often not observed with antioxidants esterified with acyl chains to vary their polarity. In this study, the nonpolar eicosyl rosmarinate (20 carbons, R20) was less effective at inhibiting lipid oxidation in oil-in-water emulsions than esters with shorter fatty acyl chains such as butyl (R4), octyl (R8), and dodecyl (R12) esters. Interestingly, in the presence of surfactant micelles, the antioxidant activity of R20 was significantly increased while the antioxidant activity of R4 and R12 was slightly decreased. The presence of surfactant micelles increased the concentration of R20 at the interface of the surfactant micelles and/or emulsion droplets as determined by partitioning studies, front face fluorescence properties, and the ability of R20 to interact with the interfacial probe, 4-hexadecylbenzenediazonium. A possible explanation for why the antioxidant activity of R20 was so dramatically increased by surfactant micelles is that a portion of the nonpolar R20 localizes in the emulsion droplet core and the surfactant micelles are able to increase the interfacial concentrations of R20 and thus its ability to scavenge free radicals produced from the decomposition of interfacial lipid hydroperoxides. PMID- 22324395 TI - Induction of multidrug resistance-associated protein 2 in liver, intestine and kidney of streptozotocin-induced diabetic rats. AB - Many studies have demonstrated that Mrp2 is highly regulated in some physiopathological situations. The aim of this study was to investigate effects of diabetes mellitus on function and expression of multidrug resistance associated protein 2 (Mrp2) in rat liver, kidney and intestine. Diabetic rats were induced by an intraperitoneal administration of streptozotocin (65 mg/kg) and randomly divided into diabetic (DM) rats and insulin-treated diabetic rats. Sulfobromophthalein (BSP), a substrate of Mrp2, was used to evaluate Mrp2 function in vivo. Data from excretion experiments demonstrated that compared with normal rats, diabetes markedly enhanced BSP excretion via bile, urine and intestinal perfusate, which contributed to the elevated plasma clearance of BSP after intravenous administration of 45 MUmol/kg BSP. Western blot results showed higher levels of hepatic, renal and intestinal Mrp2 protein in DM rats, although no difference was observed in renal Mrp2. Insulin treatment partly reversed these alterations. Induction of Mrp2 by diabetes was in parallel with the increase in bile flow, levels of biliary and plasma total bile acid (TBA), and plasma conjugated bilirubin in DM rats. Diabetes may enhance Mrp2 function and expression in liver, kidney and intestine, which might be due to insulin deficiency, increased TBA and conjugated bilirubin. PMID- 22324396 TI - Characterization of intestinal and hepatic P450 enzymes in cynomolgus monkeys with typical substrates and inhibitors for human P450 enzymes. AB - Cynomolgus monkeys are widely used to predict human pharmacokinetic and/or toxic profiles in the drug developmental stage. Characterization of cynomolgus monkey P450s such as the mRNA expression level, substrate specificity, and inhibitor selectivity were conducted to provide helpful information in designing monkey in vivo studies and monkey-to-human extrapolation. The expression levels of 12 monkey P450 mRNAs, which are considered to be important P450 subfamilies in drug metabolism, were investigated in the liver, small intestine (duodenum, jejunum, and ileum), and colon of individual monkeys. 3. In vitro activities and intrinsic clearance values were determined in monkey intestinal and liver microsomes (MIM and MLM, respectively) using nine typical oxidative reactions for human P450s. Paclitaxel 6alpha-hydroxylation, diclofenac 4'-hydroxylation, and S-mephenytoin 4'-hydroxylation showed low activities in MIM and MLM. IC50 values of eight selective inhibitors of human P450s were determined in MIM and MLM. Inhibitory effects of furafylline and sulfaphenazole were weak in monkeys on phenacetin O deethylation and diclofenac 4'-hydroxylation, respectively. These results show profiles of monkey P450s in both the intestine and liver in detail and contribute to a better understanding of the species difference in substrate specificity and inhibitor selectivity between cynomolgus monkeys and humans. PMID- 22324397 TI - Why do we treat the newborn differently? AB - End-of-life decisions are often taken in neonatology, based on widely accepted guidelines, to avoiding futile therapies. Usually, the criteria upon which these guidelines rely are different from those used for older patients, even when patients require a guardian to decide on their behalf. Main differences are the weight of parental interests and the probabilistic base of the choice. A careful analysis of the literature found three main reasons of this difference: the obsolescence of the guidelines criteria, the difficulty to distinguish between parents' and babies' interests and the neonatologist's responsibility to prolong a life with the prospective of severe disability. In conclusion, the future guidelines for newborn end-of-life decisions should follow at least the same moral criteria used for older patients. PMID- 22324398 TI - Predicting concentrations of organic chemicals in fish by using toxicokinetic models. AB - Quantification of chemical toxicity continues to be generally based on measured external concentrations. Yet, internal chemical concentrations have been suggested to be a more suitable parameter. To better understand the relationship between the external and internal concentrations of chemicals in fish, and to quantify internal concentrations, we compared three toxicokinetic (TK) models with each other and with literature data of measured concentrations of 39 chemicals. Two one-compartment models, together with the physiologically based toxicokinetic (PBTK) model, in which we improved the treatment of lipids, were used to predict concentrations of organic chemicals in two fish species: rainbow trout (Oncorhynchus mykiss) and fathead minnow (Pimephales promelas). All models predicted the measured internal concentrations in fish within 1 order of magnitude for at least 68% of the chemicals. Furthermore, the PBTK model outperformed the one-compartment models with respect to simulating chemical concentrations in the whole body (at least 88% of internal concentrations were predicted within 1 order of magnitude using the PBTK model). All the models can be used to predict concentrations in different fish species without additional experiments. However, further development of TK models is required for polar, ionizable, and easily biotransformed compounds. PMID- 22324399 TI - DNA interaction studies of a platinum(II) complex containing L-histidine and 1,10 phenanthroline ligands. AB - The aim of this study was developing coordination complexes that can be used as inorganic medicinal agents. The water soluble [Pt(phen)(His)]NO(3).3H(2)O complex in which phen=1,10-phenantheroline and His=L-histidine was synthesized and characterized using physicochemical methods. Binding interaction of this complex with calf thymus (CT) DNA was investigated by emission, absorption, circular dichroism, and viscosity measurement techniques. Upon addition of CT-DNA, changes were observed in the characteristic ultraviolet-visible (UV-Vis) bands (hypochromism) of the complex. The complex binds to CT-DNA in an intercalative mode. The calculated binding constant, K(b), was 8 +/- 0.2 * 10(4) M(-1). In addition, circular dichroism (CD) study showed that the phenanthroline ligand was inserted between the base pair stack of the double-helical structure of DNA. Also, the fluorescence spectral characteristics showed an increase in fluorescence intensity of the platinum complex in the presence of increasing amounts of DNA solution. The experimental results showed that the platinum complex binds to DNA via intercalative and hydrogen bonding mode. PMID- 22324400 TI - Chlorogenic acid, rutin and hyperoside content in Fragaria vesca, F. viridis and F. moschata in Lithuania. AB - In Lithuania, two species of the genus Fragaria L. (Rosaceae), F. vesca L. and F. viridis Weston, occur naturally in the wild and two others, F. moschata Weston and F. * ananassa Duchesne ex Rozier are found escaped from cultivation. The main objective of this study was to establish the variation pattern in the content of chlorogenic acid, rutin and hyperoside in leaves and fruits of the native Lithuanian species. In this work, the chemical polymorphisms of different Fragaria species were studied by growing plants side by side under the same cultivated field conditions. F. vesca fruits had the highest rutin (1.38 +/- 0.19 mg g(-1) DM), hyperoside (0.69 +/- 0.10 mg g(-1) DM) and chlorogenic acid (2.25 +/- 0.34 mg g(-1) DM) content, followed by F. viridis and F. moschata. Our results showed that the leaves should be taken into account as important rutin and hyperoside contributors for strawberries. PMID- 22324401 TI - Morphology evolution of TiO2 facets and vital influences on photocatalytic activity. AB - Modulation of anatase toward highly active facets has been attracting much attention, but the mechanism and photoactivity are still ambiguous. Here we demonstrate the inherent mechanisms for facets nucleation and morphology evolution, and clarify some vital influences of facets and surface nature on the photoactivity. Simply tuning the Ti/F ratio in the synthetic mixture leads to single anatase crystal exposed with different facets like {001}, {010}, or {110}. And complex sphere structure exposed with {001} facets can be formed by secondary nucleation and growth. Prolonging the hydrothermal treatment time causes selective etching on {001} facets, whereas defluorination via thermal calcination produces many pores on the surface. The photodegradation of positively and negatively charged, and zwitterionic dyes indicates that the type of reactant, adsorption mode and surface area play significant roles in photocatalysis. This work makes a step toward understanding the formation of facet-mediated structure and designing highly active materials for environmental remediation, hydrogen production, and dye-sensitized solar cells. PMID- 22324402 TI - Hydrogen spillover. Facts and fiction. PMID- 22324403 TI - Magnetic nano-Fe3O4-supported 1-benzyl-1,4-dihydronicotinamide (BNAH): synthesis and application in the catalytic reduction of alpha,beta-epoxy ketones. AB - A novel magnetically recoverable organic hydride compound was successfully constructed by using silica-coated magnetic nanoparticles as a support. An as prepared magnetic organic hydride compound, BNAH (1-benzyl-1,4 dihydronicotinamide), showed efficient activity in the catalytic reduction of alpha,beta-epoxy ketones. After reaction, the magnetic nanoparticle-supported BNAH can be separated by simple magnetic separation which made the separation of the product easier. PMID- 22324404 TI - Anomalous coronary circulation: left anterior descending and left circumflex coronary arteries arising from the right sinus of valsalva. AB - Approximately 1% of adults who undergo cardiac catheterization have coronary anomalies. Patients may present with chest pain, arrhythmias, presyncope, and sometimes sudden cardiac death. Multidetector computed tomography (MDCT) is an excellent tool for identifying coronary artery anomalies and defining their course and relationship to the great vessels and surrounding structures; its value is incremental to conventional angiography. We present a rare case of a coronary anomaly involving three separate ostia at the right sinus of Valsalva for the left and right coronary vessels. PMID- 22324405 TI - Formation and reactivity of 3-diazopyridinium cations and influence on their reductive electrografting on glassy carbon. AB - The in situ generation of 3-diazonium cations from 3-aminopyridine and their subsequent stability under experimental conditions used for electrografting of pyridine groups were investigated by spectroscopy and electrochemistry. UV spectroscopy revealed the rapid kinetics for the reaction of 3-aminopyridine with sodium nitrite in HCl to form the 3-diazopyridinium cation with a second-order rate constant of 550 +/- 20 L mol(-1) s(-1) at 22 degrees C. UV spectroscopy showed that the 3-diazopyridinium ion was relatively unstable and its transformation into 3-hydroxypyridine was proven by (1)H NMR. Its hydrolytic decomposition was investigated by NMR and followed first-order kinetics with a rate constant of (53 +/- 5) * 10(-3) s(-1) at 22 degrees C. These results enable us to establish the appropriate conditions for the electrografting of pyridine from the corresponding diazonium cations generated in situ. The electrochemical modification of glassy carbon electrodes with pyridine was characterized by cyclic voltammetry and the resulting grafted layer by electrochemical impedance spectroscopy in the presence of Fe(CN)(6)(3-/4-) as redox probes. The effect of diazotization time before electrochemical reduction on the blocking effect of the grafted layer was investigated and showed that an increase of the diazotization time led to less efficient grafting. The presence of immobilized pyridine on the electrode surface was demonstrated by X-ray photoelectron spectroscopy measurements, and a surface coverage of 8.8 * 10(-10) mol cm(-2) was estimated for the grafted pyridine groups. The significance of these results for researchers using the in situ generation approach for electrochemical and chemical grafting is discussed. PMID- 22324406 TI - Emerging brominated flame retardants in the sediment of the Great Lakes. AB - The concentrations of 13 currently used brominated flame retardants (BFRs) were analyzed in 16 sediment cores collected from the North American Great Lakes. Among them, 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), decabromodiphenyl ethane (DBDPE), hexabromocyclododecane (HBCD), 1,2-dibromo-4-(1,2 dibromoethyl)cyclohexane (TBECH), and hexachlorocyclopentadienyl dibromocyclooctane (HCDBCO) were more frequently detected than others. In general, these emerging BFRs have much lower concentrations than polybromodiphenyl ethers (PBDEs) and dechloranes. Inventories of the five BFRs named above, given on a logarithm basis, were found to decrease linearly with the increasing latitude of the sampling locations, but with weaker statistics than those previously reported for the dechloranes. Logarithm of surface fluxes, on the other hand, was found to be a better parameter in correlating with the longitude. With regard to time trends, the exponential increases in concentrations of these BFRs, particularly DBDPE and BTBPE, in recent years are particularly disturbing. The sediment concentration of DBDPE doubles every 3-5 years in Lake Michigan, and approximately every 7 years in Lake Ontario. The corresponding doubling times for BTBPE are about 5 and 7 years in Lakes Ontario and Michigan, respectively, although declines or leveling off were observed in the top sediment layers in Lake Ontario. In contrast to PCBs, PBDEs, and most dechloranes, the correlations between the surface concentration of emerging BFRs and the latitude or longitude of the sampling sites were not strengthened by normalization of the concentration based on the organic matter content of the sediment. PMID- 22324407 TI - Medicinal mushrooms for glycemic control in diabetes mellitus: history, current status, future perspectives, and unsolved problems (review). AB - Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia with defects in insulin secretion and/or insulin resistance. Despite great efforts that have been made in the understanding and management of diabetes, its prevalence continues to grow. Recent discoveries have opened up an exciting opportunity for developing new types of therapeutics from medicinal mushrooms to control DM and its complications. To date, more and more active components including polysaccharides and their protein complexes, dietary fibers, and other compounds extracted from fruiting bodies, cultured mycelium, or cultured broth of medicinal mushrooms have been reported as to having anti hyperglycemic activity. These compounds exhibit their antidiabetic activity via different mechanisms. This article presents an overview of the multiple aspects of diabetes mellitus and the efficacy and mechanism of medicinal mushrooms for glucose control in diabetes, including the inhibition of glucose absorption, protection of beta-cell damage, increase of insulin release, enhancement of antioxidant defense, attenuation of inflammation, modulation of carbohydrate metabolism pathway, and regulation of insulin-dependent and insulin-independent signaling pathways. However, there is insufficient evidence to draw definitive conclusions about the efficacy of individual medicinal mushrooms for diabetes. In addition, the wide variability, the lack of standards for production, and the lack of testing protocols to assess product quality are still problems in producing medicinal mushroom products. Moreover, well-designed randomized controlled trials with long-term consumption are needed to guarantee the bioactivity and safety of medicinal mushroom products for diabetic patients. PMID- 22324408 TI - Antitumor effect of culinary-medicinal oyster mushroom, Pleurotus ostreatus (Jacq.: Fr.) P. Kumm., derived protein fraction on tumor-bearing mice models. AB - Previously, we reported the in vitro anticancer and immunomodulatory effect of a protein fraction designated as Cibacron blue affinity purified protein (CBAEP) obtained from the culinary-medicinal oyster mushroom, Pleurotus ostreatus. In the present study, we investigated the in vivo antitumor potential of CBAEP in different tumor-bearing mice models and studied the detailed mechanism of tumor regression in Dalton lymphoma (DL)-bearing mice. The lethal dose (LD50) of CBAEP was found to be 55 mg/kg body weight and sublethal doses (5 mg/kg and 10 mg/kg body weight) showed a prolonged tumor survival time in DL, Sarcoma-180, and B16F0 melanoma tumor-bearing mice. Further, CBAEP reduced about 35.68 and 51.43% DL cell growth in 5 and 10 mg/kg body weight, respectively. The in vivo CBAEP treatment showed an apoptotic feature as demonstrated in morphological study and sub-G0/G1 population in cell cycle and Western blot of DL cells. CBAEP also activated immunosuppression condition in DL tumor-bearing host. It also stimulated immune cells in the presence of nonspecific immunostunulator (LPS and ConA) ex vivo as well as enhanced Th1 response with production of TNF-alpha, IFN gamma, and IL-2. Moreover, it activated tumor-associated macrophages and NK cells. The present findings revealed the potent antitumor property of CBAEP, which might help in developing a new anticancer drug. PMID- 22324409 TI - Immunomodulation of bone marrow macrophages by GLIS, a proteoglycan fraction from Lingzhi or Reishi medicinal mushroom Ganoderma lucidium (W.Curt.:Fr.) P. Karst. AB - The immunomodulatory effect of GLIS (Lingzhi or Reishi medicinal mushroom Ganoderma lucidum immunomodulating substance) on macrophages has been investigated as part of ongoing research into the anticancer properties of this mushroom. Proliferation of bone marrow macrophages (BMMs) was enhanced by GLIS in a dose-dependent manner. Microscopic examination revealed that numerous GLIS treated BMMs were enlarged and formed pseudopodia. Exposure of BMMs to GLIS resulted in significant increases in NO production, induction of cellular respiratory burst activity, and increased levels of IL-1beta, IL-6, IL-12p35, IL 12p40, IL-18, and TNF-alpha gene expression and levels of TNF-alpha, IL-1beta, and IL-12 secretion. Our data indicate that GLIS activates the immune system by modulating cytokine production. PMID- 22324410 TI - Indole compounds in some culinary-medicinal higher basidiomycetes from Poland. AB - Methanolic extracts of two species collected from natural habitats in Poland, Boletus edulis and Suillus luteus, and one species from a commercial source, Pleurotus ostreatus, were analyzed for the presence of non-hallucinogenic indole compounds. The contents of indole compounds in these species were both qualitatively and quantitatively diverse, ranging from 0.01 to 34.11 mg/100 g d.w. Two of 11 tested indole compounds, 5-hydroxytryptophan (0.18, 2.08, 1.63 mg/100 g d.w.) and serotonin (6.52, 10.14, 34.11 mg/100 g d.w.), were present in all three species under study. B. edulis and S. luteus were found to contain L tryptophan (0.39 and 2.61 mg/100g d.w.) and melatonin (0.68 and 0.71 mg/100 g d.w.). Tryptamine was present in two species, i.e., B. edulis (1.17 mg/100 g d.w.) and in P. ostreatus (0.91 mg/100 g d.w.), in which slight amounts of indole acetonitrile (0.04 and 0.01 mg/100 g d.w., respectively) were also identified. Indoleacetic acid was a common metabolite for P. ostreatus and S. luteus and its contents amounted to 0.21 and 0.04 mg/100 g d.w., respectively. Indole compounds degradation products kynurenic acid (2.63 mg/100 g d.w.) and kynurenine sulfate were (19.57 mg/100 g d.w.) were observed only in S. luteus. PMID- 22324411 TI - Enhanced production of medicinal polysaccharide by submerged fermentation of Lingzhi or Reishi medicinal mushroom Ganoderma lucidium (W.Curt.:Fr.) P. Karst. Using statistical and evolutionary optimization methods. AB - Statistical and evolutionary optimization of media composition was employed for the production of medicinal exopolysaccharide (EPS) by Lingzhi or Reishi medicinal mushroom Ganoderma lucidium MTCC 1039 using soya bean meal flour as low cost substrate. Soya bean meal flour, ammonium chloride, glucose, and pH were identified as the most important variables for EPS yield using the two-level Plackett-Burman design and further optimized using the central composite design (CCD) and the artificial neural network (ANN)-linked genetic algorithm (GA). The high value of coefficient of determination of ANN (R2 = 0.982) indicates that the ANN model was more accurate than the second-order polynomial model of CCD (R2 = 0.91) for representing the effect of media composition on EPS yield. The predicted optimum media composition using ANN-linked GA was soybean meal flour 2.98%, glucose 3.26%, ammonium chloride 0.25%, and initial pH 7.5 for the maximum predicted EPS yield of 1005.55 mg/L. The experimental EPS yield obtained using the predicted optimum media composition was 1012.36 mg/L, which validates the high degree of accuracy of evolutionary optimization for enhanced production of EPS by submerged fermentation of G. lucidium. PMID- 22324412 TI - Morpho-physiological diversity between Lingzhi or Reishi medicinal mushroom Ganoderma lucidium (W. Curt.:Fr.) P. Karst. and G. carnosum pat. AB - Two weakly differentiated taxa, Ganoderma lucidum and G. carnosum, were compared in their sufficient morphological and physiological features. The obtained results showed that dimensions of basidiospores and pileocystidia were insignificantly different, while pore shape and dimensions have shown greater diversity with average diameter of 138.46 MUm in G. carnosum and 238.34 MUm in G. lucidum. Mycelial growth rate was higher in G. lucidum (8.39 mm day-1) than in G. carnosum (6.02 mm day-1). G. lucidum was also a slightly better producer of biomass and extracellular polysaccharides (28.16 g L-1 and 1.42 mg mL-1, respectively) than G. carnosum (23.68 g L-1 and 0.35 mg mL-1, respectively). However, a higher amount of synthesized intracellular polysaccharides was noted in G. carnosum than in G. lucidum (40.00 mg g-1 and 30.00 mg g-1 of dry biomass, respectively). Higher activity levels of Mn-oxidizing peroxidases were obtained in G. carnosum, while G. lucidum was a better laccase producer. In G. carnosum, corn stem/NH4NO3 medium with nitrogen concentration of 20 mM was the optimum for Mn-dependent peroxidase production (88.00 U L-1), while the highest versatile peroxidase activity was detected in the medium with grapevine sawdust and 10 mM of nitrogen (80.80 U L-1). Wheat straw was the best carbon source for laccase synthesis in G. lucidum (55.75 U L-1). PMID- 22324413 TI - Proteomic analysis of differently cultured endemic medicinal mushroom Antrodia cinnamomea T.T. Chang et W.N. Chou from Taiwan. AB - Antrodia cinnamomea is peculiar to Taiwan. It only grows on one host and is highly valued as an important component of several traditional Chinese medicines. In this study, the different protein expression profiles of artificially cultivated vegetative mycelium and wild-type basidiomatal fruiting bodies were compared and unique protein spots from wild-type basidiomatal fruiting body were investigated using 2D polyacrylamide gel electrophoresis and LC-MS/MS protein identification. Most of the wild-type proteins not seen in the artificially cultivated mycelium were associated to function in metabolism, cell stress, ROS scavenging, and cell growth. Several proteins from wild-type basidiomes, such as catalase, aryl-alcohol dehydrogenase, S-adenosyl-L-homocysteine hydrolase, intradiol dioxygenase, haloacid dyhydrogenase, alpha- and beta-form tubulin, prohibitin, septin, chaperone, and HSP90 ATPase, showed higher expression than those from artificially cultured mycelium at the mRNA level. PMID- 22324414 TI - Mycosynthesis of silver nanoparticles using Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (W. Curt.:Fr.) P. Karst. and their role as antimicrobials and antibiotic activity enhancers. AB - Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum, has been used over the ages as highly medicinal herb in the Orient. Many useful properties of this fungus are still being studied; we report here a new facet of this "elixir of life" as a mycosource for synthesis of metal nanoparticles. Treating the extracellular suspension filtrate of the mycelia of G. lucidum with silver nitrate reduces the metal ions to nanoparticles. Optical detection followed by confirmation through spectroscopic analysis suggests that this fungus can be used for the purpose of safe and sure synthesis of silver nanoparticles, demand for which is growing day by day in all fields of human life. LM-20 analysis of these G. lucidum-synthesised nanoparticles reveals the polydispersity and distribution of silver nanoparticles in the range of 10-70 nm with an average size of 45 nm and a concentration of 0.37 x 108 particles/mL. FT-IR spectrum confirms the stability of these nanoparticles due to presence of amide linkages and protein capping. These nanoparticles have shown strong bactericidal activity against test pathogens Staphylococcus aureus and Escherichia coli, and also exhibited their efficiency in enhancing the activity of the synthetic antibiotic tetracycline. The method of synthesising silver nanoparticles and its bactericidal effect discussed here can be used for environment-friendly and economically feasible production for different applications where chemically synthesized nanoparticles cause undesirable effects. PMID- 22324415 TI - Atmospheric plasma enhances wettability and cell spreading on dental implant metals. AB - OBJECTIVES: Treatment regimens, which predictably support re-osseointegration of implants with peri-implantitis, are needed. Increased wettability may be an important factor for re-osseointegration. In this study, a cold atmospheric pressure gas-discharge plasma was applied to reduce water contact angles on titanium discs with different surface topography and to improve the spreading of osteoblastic cells. MATERIAL AND METHODS: An argon plasma jet with different oxygen admixtures was used to treat titanium discs with different topologies, i.e. machined, SLA((r)) , SLActive((r)) , diamond bur-treated or Airflow((r)) treated. Water contact angles were measured before and after plasma treatment. The spreading behaviour of human osteoblastic cells was investigated. RESULTS: Contact angle of titanium discs (baseline values: 68 degrees -117 degrees ) were significantly reduced close to 0 degrees irrespective of surface topography after the application of argon plasma with 1.0% oxygen admixture for 60 s or 120 s. The cell size of osteoblastic cells grown on argon-oxygen-plasma-treated titanium discs was significantly larger than on non-treated surfaces (p < 0.001) irrespective of surface topography. CONCLUSIONS: Plasma treatment reduced contact angle and supported spreading of osteoblastic cells. The application of cold plasma may be supportive in the treatment of peri-implant lesions and may improve the process of re-osseointegration. PMID- 22324417 TI - Bevacizumab used for the treatment of severe, refractory perilesional edema due to an arteriovenous malformation treated with stereotactic radiosurgery. AB - The authors present a case of an arteriovenous malformation of the central sulcus treated with Gamma Knife surgery. The patient developed perilesional edema 9 months after treatment and experienced severe headache and hemiparesis. Her symptoms were refractory to corticosteroid therapy and pain management. She was subsequently treated with bevacizumab with striking improvement in her symptoms and results of neuroimaging studies. This is the first time that bevacizumab has been used to control severe refractory perilesional edema related to an intracranial arteriovenous malformation. PMID- 22324418 TI - Improvement of neurological recovery and stimulation of neural progenitor cell proliferation by intrathecal administration of Sonic hedgehog. AB - OBJECT: Sonic hedgehog (Shh) is a glycoprotein molecule that has been shown to be associated with the proliferative capacity of endogenous neural precursor cells during embryonic development. It has also been shown to regulate the proliferative capacity of neural stem cells in the adult subventricular zone (SVZ), which are also upregulated in animal models of ischemic stroke. In the present study, the effects of exogenous administration of intrathecal Shh protein were examined in the setting of a rodent model of ischemic stroke, with particular attention given to endogenous neural stem cell proliferation and migration as well as inducible differences in behavioral recovery. METHODS: A rodent model of ischemic stroke was created using the intraluminal suture method of reversible middle cerebral artery occlusion. Animals were treated with intrathecal administration of Shh protein at 24 hours after the onset of the stroke. Behavioral testing was performed, and the animals were killed for measurements of infarct volume 7 days after stroke. Immunohistochemical staining was performed and measurements of cellular proliferation were obtained, with a focus on the proportion and distribution of neural progenitor cells in the SVZ. These values were compared across experimental groups. RESULTS: Treatment with intrathecal Shh protein resulted in significant improvement in behavioral function compared with the control group, with a significant reduction of ischemic tissue in the cerebral hemisphere. An increase of nestin immunoreactive cells was observed along the SVZ. CONCLUSIONS: Intrathecal Shh agonist at doses that upregulate spinal cord GLI1 transcription increases the population of neural precursor cells after spinal cord injury in adult rats. Intrathecal administration of Shh protein appears to have a neuroprotective effect in animal models of ischemic stroke and is associated with improved behavioral recovery, which may be related to its effects on neurogenesis in the SVZ and could be associated with improved functional recovery. PMID- 22324419 TI - Pressure-derived versus pressure wave amplitude-derived indices of cerebrovascular pressure reactivity in relation to early clinical state and 12 month outcome following aneurysmal subarachnoid hemorrhage. AB - OBJECT: Indices of cerebrovascular pressure reactivity (CPR) represent surrogate markers of cerebral autoregulation. Given that intracranial pressure (ICP) wave amplitude-guided management, as compared with static ICP-guided management, improves outcome following aneurysmal subarachnoid hemorrhage (SAH), indices of CPR derived from pressure wave amplitudes should be further explored. This study was undertaken to investigate the value of CPR indices derived from static ICP arterial blood pressure (ABP) values (pressure reactivity index [PRx]) versus ICP ABP wave amplitudes (ICP-ABP wave amplitude correlation [IAAC]) in relation to the early clinical state and 12-month outcome in patients with aneurysmal SAH. METHODS: The authors conducted a single-center clinical trial enrolling patients with aneurysmal SAH. The CPR indices of PRx and IAAC of Week 1 after hemorrhage were related to the early clinical state (Glasgow Coma Scale [GCS] score) and 12 month outcome (modified Rankin Scale score). RESULTS: Ninety-four patients were included in the study. The IAAC, but not the PRx, increased with decreasing GCS score; that is, the higher the IAAC, the worse the clinical state. The PRx could differentiate between survivors and nonsurvivors only, whereas the IAAC clearly distinguished the groups "independent," "dependent," and "dead." In patients with an average IAAC >= 0.2, mortality was approximately 3-fold higher than in those with an IAAC < 0.2. CONCLUSIONS: The IAAC, which is based on single ICP-ABP wave identification, relates significantly to the early clinical state and 12-month outcome following aneurysmal SAH. Impaired cerebrovascular pressure regulation during the 1st week after a bleed relates to a worse outcome. CLINICAL TRIAL REGISTRATION NO.: NCT00248690. PMID- 22324421 TI - Spontaneous resolution of a Chiari malformation Type I and syrinx after supratentorial craniotomy for excision of a cavernous malformation. AB - The pathogenesis of Chiari malformation Type I (CM-I) and associated syringomyelia is incompletely understood. Patients often present in middle age with incidental or minimally symptomatic CM-I, whose management is controversial. One option is clinical and radiographic observation of asymptomatic and minimally symptomatic patients. The authors here present the case of a 36-year-old woman who had been monitored for 6 years for a minimally symptomatic CM-I and cervicothoracic syrinx. After 5 years of follow-up, she suffered spontaneous rupture of a cerebral cavernous malformation when she was 27 weeks pregnant. The ruptured cavernous malformation and hematoma were operatively managed via a right frontal craniotomy. Ten months after the craniotomy for resection of the ruptured cavernous malformation, follow-up MRI demonstrated resolution of the CM-I and syrinx. Few similar cases have been reported in adults. This case argues for the presence of dynamic factors in the development and maintenance of CM-I and supports the nonoperative treatment of asymptomatic and minimally symptomatic patients. PMID- 22324420 TI - Neuroprotective and neurorestorative effects of thymosin beta4 treatment initiated 6 hours after traumatic brain injury in rats. AB - OBJECT: Thymosin beta4 (Tbeta4) is a regenerative multifunctional peptide. The aim of this study was to test the hypothesis that Tbeta4 treatment initiated 6 hours postinjury reduces brain damage and improves functional recovery in rats subjected to traumatic brain injury (TBI). METHODS: Traumatic brain injury was induced by controlled cortical impact over the left parietal cortex in young adult male Wistar rats. The rats were randomly divided into the following groups: 1) saline group (n = 7); 2) 6 mg/kg Tbeta4 group (n = 8); and 3) 30 mg/kg Tbeta4 group (n = 8). Thymosin beta4 or saline was administered intraperitoneally starting at 6 hours postinjury and again at 24 and 48 hours. An additional group of 6 animals underwent surgery without TBI (sham-injury group). Sensorimotor function and spatial learning were assessed using the modified Neurological Severity Score and the Morris water maze test, respectively. Animals were euthanized 35 days after injury, and brain sections were processed to assess lesion volume, hippocampal cell loss, cell proliferation, and neurogenesis after Tbeta4 treatment. RESULTS: Compared with saline administration, Tbeta4 treatment initiated 6 hours postinjury significantly improved sensorimotor functional recovery and spatial learning, reduced cortical lesion volume and hippocampal cell loss, and enhanced cell proliferation and neurogenesis in the injured hippocampus. The high dose of Tbeta4 showed better beneficial effects compared with the low-dose treatment. CONCLUSIONS: Thymosin beta4 treatment initiated 6 hours postinjury provides both neuroprotection and neurorestoration after TBI, indicating that Tbeta4 has promising therapeutic potential in patients with TBI. These data warrant further investigation of the optimal dose and therapeutic window of Tbeta4 treatment for TBI and the associated underlying mechanisms. PMID- 22324422 TI - A meta-analysis of predictors of seizure freedom in the surgical management of focal cortical dysplasia. AB - OBJECT: Focal cortical dysplasia (FCD) is one of the most common causes of medically refractory epilepsy leading to surgery. However, seizure control outcomes reported in isolated surgical series are highly variable. As a result, it is not clear which variables are most crucial in predicting seizure freedom following surgery for FCD. The authors' aim was to determine the prognostic factors for seizure control in FCD by performing a meta-analysis of the published literature. METHODS: A MEDLINE search of the published literature yielded 37 studies that met inclusion and exclusion criteria. Seven potential prognostic variables were determined from these studies and were dichotomized for analysis. For each variable, individual studies were weighted by inverse variance and combined to generate an odds ratio favoring seizure freedom. The methods complied with a standardized meta-analysis reporting protocol. RESULTS: Two thousand fourteen patients were included in the analysis. The overall rate of seizure freedom (Engel Class I) among patients undergoing surgery for FCD in the cohort of studies was 55.8% +/- 16.2%. Partial seizures, a temporal location, detection with MRI, and a Type II Palmini histological classification were associated with higher rates of postoperative seizure control. As a treatment-related factor, complete resection of the anatomical or electrographic abnormality was the most important predictor overall of seizure freedom. Neither age nor electroencephalographic localization of the ictal onset significantly affected seizure freedom after surgery. CONCLUSIONS: Using a large population cohort pooled from the published literature, an analysis identified important factors that are prognostic in patients with epilepsy due to FCD. The most important of these factors-diagnostic imaging and resection-provide modalities through which improvements in the impact of FCD can be effected. PMID- 22324423 TI - Association of employment and working conditions with physical and mental health symptoms for people with fibromyalgia. AB - PURPOSE: This study examines physical and mental health symptoms among people with fibromyalgia (FM) by employment status and working conditions. METHOD: Secondary data analysis of the 2007 National Fibromyalgia Association Questionnaire study resulted in employment and symptom information for 1702 people of working age with FM. In this cross-sectional internet study, six factors of symptom clusters (physical, mental health, sleeping, concentration, musculoskeletal, support) were seen in the data. Linear regression models used employment, age, income, gender, and education to predict symptom clusters. Among those employed, working conditions were also associated with symptom severity. RESULTS: In the predominately female sample, 51% were working. Of these, 70% worked over 30 hours/week and half had flexible hours. Employment, higher income, and education were strongly associated with fewer symptoms. Working conditions, including level of physical and mental exertion required on the job as well as coworkers' understanding of FM, were related to symptoms, particularly physical and mental health symptoms. Many participants reported modifying their work environment (66%) or changing occupations (33%) due to FM. CONCLUSIONS: Work modifications could allow more people with FM to remain employed and alleviate symptoms. Persons with FM should be counseled to consider what elements of their work may lead to symptom exacerbation. PMID- 22324424 TI - An integrated approach to optimizing skin delivery of cosmetic and pharmaceutical actives. AB - The academic literature on skin delivery provides countless examples of scientific insights into specific aspects of the overall process. For the practical formulator, however, it is difficult to know how to combine such insights in a way that fits into the realities of commercial formulations. In this study, five key principles are combined into an integrated approach that can be applied to real-world formulations. Given the complexities of skin science, the integrated approach cannot be expected to be highly precise. Instead, it is intended as a way for a formulation team to balance the many conflicting issues. The predictions are sufficiently specific to be examined by those with the appropriate analytical resources and data on formulation efficacy. It is hoped that such challenges will allow the approach to be refined for the future. PMID- 22324425 TI - A comparison of the acid-inhibitory effects of esomeprazole and rabeprazole in relation to pharmacokinetics and CYP2C19 polymorphism. AB - BACKGROUND: Esomeprazole and rabeprazole are metabolised in the liver by means of the CYP2C19 enzyme, which has several functional genetic polymorphisms. Among Caucasians, 70% of the population has a fast metaboliser phenotype, 25-30% an intermediate and 2-5% a slow metaboliser phenotype. It is unknown whether different PPIs are affected to the same extent by these phenotypic differences. AIM: To compare the acid-inhibitory effects of esomeprazole 40 mg and rabeprazole 20 mg in relation to CYP2C19 genotype and pharmacokinetics. METHODS: Eighteen healthy Helicobacter pylori-negative Caucasian subjects with CYP2C19*2-*6 and *17 genotype were included in a randomised investigator-blinded crossover study with esomeprazole 40 mg and rabeprazole 20 mg. Intragastric 24-h pH-monitoring was performed on days 0, 1 and 5 of oral dosing. RESULTS: Onset of acid inhibition during the first 4 h after administration did not differ significantly between PPIs. During the upright period, the proportion of time with pH >4 was significantly higher with esomeprazole compared to rabeprazole (52.2 vs. 40.3%, P = 0.003). At day 1 and 5, acid inhibition was significantly greater with esomeprazole than with rabeprazole (median intragastric pH: day 1: 3.7 vs. 3.0, P = 0.008; day 5: 4.7 vs. 3.8, P < 0.001; percentage of time pH >4: day 1: 45 vs. 39%, P = 0.054; day 5: 65 vs. 48%, P < 0.001). Differences in acid inhibition between wt/wt and wt/*2 genotype were significant for both PPIs. CONCLUSIONS: Once-daily dosing with esomeprazole 40 mg provides a more effective and faster acid-inhibitory effect than rabeprazole 20 mg. The acid-inhibitory effect of esomeprazole and rabeprazole are both influenced by CYP2C19 polymorphism. PMID- 22324426 TI - The RS domain of Arabidopsis splicing factor RRC1 is required for phytochrome B signal transduction. AB - Plants monitor the light environment through informational photoreceptors that include phytochromes. In seedling de-etiolation, phytochrome B (phyB), which is the most important member of the phytochrome family, interacts with transcription factors to regulate gene expression and transduce light signals. In this study, we identified rrc1 (reduced red-light responses in cry1cry2 background 1), an Arabidopsis mutant that is impaired in phyB-mediated light responses. A genetic analysis demonstrated that RRC1 affected light signaling in a phyB-dependent manner. RRC1 encodes an ortholog of the human potential splicing factor SR140. The RRC1 polypeptide contains a C-terminal arginine/serine-rich (RS) domain that is important for the regulation of alternative splicing. Although the complete loss of RRC1 caused pleiotropic developmental abnormalities, the deletion of the RS domain specifically reduced phyB signaling and caused aberrant alternative splicing of several SR protein genes. Moreover, semi-quantitative RT-PCR analysis revealed that the alternative splicing patterns of some of the SR protein genes were altered in a red-light-dependent manner, and that these responses were reduced in both phyB and rrc1 mutants. These findings suggest that the regulation of alternative splicing by the RS domain of RRC1 plays an important role in phyB signal transduction. PMID- 22324427 TI - Virtual implant planning in the edentulous maxilla: criteria for decision making of prosthesis design. AB - OBJECTIVES: To evaluate prosthetic parameters in the edentulous anterior maxilla for decision making between fixed and removable implant prosthesis using virtual planning software. MATERIAL AND METHODS: CT- or DVT-scans of 43 patients (mean age 62 +/- 8 years) with an edentulous maxilla were analyzed with the NobelGuide software. Implants (>=3.5 mm diameter, >=10 mm length) were virtually placed in the optimal three-dimensional prosthetic position of all maxillary front teeth. Anatomical and prosthetic landmarks, including the cervical crown point (C Point), the acrylic flange border (F-Point), and the implant-platform buccal-end (I-Point) were defined in each middle section to determine four measuring parameters: (1) acrylic flange height (FLHeight), (2) mucosal coverage (MucCov), (3) crown-Implant distance (CID) and (4) buccal prosthesis profile (ProsthProfile). Based on these parameters, all patients were assigned to one of three classes: (A) MucCov <= 0 mm and ProsthProfile>=45(0) allowing for fixed prosthesis, (B) MucCov = 0-5 mm and/or ProsthProfile = 30(0) -45(0) probably allowing for fixed prosthesis, and (C) MucCov >= 5 mm and/or ProsthProfile <= 30(0) where removable prosthesis is favorable. Statistical analyses included descriptive methods and non-parametric tests. RESULTS: Mean values were for FLHeight 10.0 mm, MucCov 5.6 mm, CID 7.4 mm, and ProsthProfile 39.1(0) . Seventy percent of patients fulfilled class C criteria (removable), 21% class B (probably fixed), and 2% class A (fixed), while in 7% (three patients) bone volume was insufficient for implant planning. CONCLUSIONS: The proposed classification and virtual planning procedure simplify the decision-making process regarding type of prosthesis and increase predictability of esthetic treatment outcomes. It was demonstrated that in the majority of cases, the space between the prosthetic crown and implant platform had to be filled with prosthetic materials. PMID- 22324428 TI - Characterization of the hypothermic effects of imidazoline I2 receptor agonists in rats. AB - BACKGROUND AND PURPOSE Imidazoline I(2) receptors have been implicated in several CNS disorders. Although several I(2) receptor agonists have been described, no simple and sensitive in vivo bioassay is available for studying I(2) receptor ligands. This study examined I(2) receptor agonist-induced hypothermia as a functional in vivo assay of I(2) receptor agonism. EXPERIMENTAL APPROACH Different groups of rats were used to examine the effects of I(2) receptor agonists on the rectal temperature and locomotion. The pharmacological mechanisms were investigated by combining I(2) receptor ligands and different antagonists. KEY RESULTS All the selective I(2) receptor agonists examined (2-BFI, diphenyzoline, phenyzoline, CR4056, tracizoline, BU224 and S22687, 3.2-56 mg.kg( 1) , i.p.) dose-dependently and markedly decreased the rectal temperature (hypothermia) in rats, with varied duration of action. Pharmacological mechanism of the observed hypothermia was studied by combining the I(2) receptor agonists (2-BFI, BU224, tracizoline and diphenyzoline) with imidazoline I(2 ) receptor/ alpha(2) adrenoceptor antagonist idazoxan, selective I(1) receptor antagonist efaroxan, alpha(2) adrenoceptor antagonist/5-HT(1A) receptor agonist yohimbine. Idazoxan but not yohimbine or efaroxan attenuated the hypothermic effects of 2 BFI, BU224, tracizoline and diphenyzoline, supporting the I(2) receptor mechanism. In contrast, both idazoxan and yohimbine attenuated hypothermia induced by the alpha(2) adrenoceptor agonist clonidine. Among all the I(2) receptor agonists studied, only S22687 markedly increased the locomotor activity in rats. CONCLUSIONS AND IMPLICATIONS Imidazoline I(2) receptor agonists can produce hypothermic effects, which are primarily mediated by I(2) receptors. These data suggest that I(2) receptor agonist-induced hypothermia is a simple and sensitive in vivo assay for studying I(2) receptor ligands. PMID- 22324429 TI - The chalcone flavokawain B induces G2/M cell-cycle arrest and apoptosis in human oral carcinoma HSC-3 cells through the intracellular ROS generation and downregulation of the Akt/p38 MAPK signaling pathway. AB - Chalcones have been described to represent cancer chemopreventive food components that are rich in fruits and vegetables. In this study, we examined the anti-oral cancer effect of flavokawain B (FKB), a naturally occurring chalcone isolated from Alpinia pricei (shell gingers), and revealed its molecular mechanism of action. Treatment of human oral carcinoma (HSC-3) cells with FKB (1.25-10 MUg/mL; 4.4-35.2 MUM) inhibited cell viability and caused G(2)/M arrest through reductions in cyclin A/B1, Cdc2, and Cdc25C levels. Moreover, FKB treatment resulted in the induction of apoptosis, which was associated with DNA fragmentation, mitochondria dysfunction, cytochrome c and AIF release, caspase-3 and caspase-9 activation, and Bcl-2/Bax dysregulation. Furthermore, increased Fas activity and procaspase-8, procaspase-4, and procaspase-12 cleavages were accompanied by death receptor and ER-stress, indicating the involvement of mitochondria, death-receptor, and ER-stress signaling pathways. FKB induces apoptosis through ROS generation as evidenced by the upregulation of oxidative stress markers HO-1/Nrf2. This mechanism was further confirmed by the finding that the antioxidant N-acetylcysteine (NAC) significantly blocked ROS generation and consequently inhibited FKB-induced apoptosis. Moreover, FKB downregulated the phosphorylation of Akt and p38 MAPK, while their inhibitors LY294002 and SB203580, respectively, induced G(2)/M arrest and apoptosis. The profound reduction in cell number was observed in combination treatment with FKB and Akt/p38 MAPK inhibitors, indicating that the disruption of Akt and p38 MAPK cascades plays a functional role in FKB-induced G(2)/M arrest and apoptosis in HSC-3 cells. PMID- 22324430 TI - The cognitive rehabilitation of limb apraxia in patients with stroke. AB - Apraxia is a higher level motor deficit that occurs when processing a goal directed action. The apraxic deficit can manifest itself in absence of sensory input deficits or motor output deficits, neglect, frontal inertia or dementia. According to a clinical classification still largely in use, there are two main forms of limb apraxia: ideomotor (IMA) and ideational (IA), observed when a patient is required to imitate a gesture or use an object, respectively. In the present review, we examined only the cognitive treatments of both types of limb apraxia of a vascular aetiology. Despite the high prevalence of limb apraxia caused by left brain damage, and the fact that apraxia has been known for over a century, the literature regarding its rehabilitation is still very limited. This is partly due to the nature of the recovery from the deficit, and in part to the automatic-voluntary dissociation. Here we review those treatments that have proved most successful in helping patients to recover from limb apraxia. PMID- 22324431 TI - Bromotheoynic acid, a brominated acetylenic acid from the marine sponge Theonella swinhoei. AB - A new brominated C(17) acetylenic acid (1) designated as bromotheoynic acid has been isolated from the marine sponge Theonella swinhoei, collected off the coast of Tanegashima, Kagoshima Prefecture, Japan. The structure was determined on the basis of the analysis of its extensive 2D NMR spectroscopic data as well as HRMS. Bromotheoynic acid (1) inhibited maturation of starfish oocytes and cell division of fertilised starfish eggs. Bromotheoynic acid (1) also inhibited proliferation of human leukaemia U937 and HL60 cells, human lung cancer A549 and H1299 cells, and human embryonic kidney 293 (HEK293) cells. PMID- 22324432 TI - Photochemical grafting and patterning of organic monolayers on indium tin oxide substrates. AB - Covalently attached organic layers on indium tin oxide (ITO) surfaces were prepared by the photochemical grafting with 1-alkenes. The surface modification was monitored with static water contact angle, X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM) measurements. Hydrophobic methyl terminated ITO surfaces can be obtained via the grafting of tetradec-1-ene, whereas the attachment of omega-functionalized 1-alkenes leads to functionalized ITO surfaces. The use of a C=C-Ge(CH(3))(3) terminus allows for facile tagging of the surface with an azido group via a one-pot deprotection/click reaction, resulting in bio/electronically active interfaces. The combination of nonaggressive chemicals (alkenes), mild reaction conditions (room temperature), and a light-induced grafting that facilitates the direct patterning of organic layers makes this simple approach highly promising for the development of ITO based (bio)electronic devices. PMID- 22324433 TI - Effect of blood donation mediated volume reduction on right ventricular function parameters in healthy subjects. AB - PURPOSE: We aimed to investigate the effect of controlled and limited volume change by the blood donation model to the right ventricular (RV) function via different echocardiographic parameters in healthy adults. METHODS: Study population was composed of 71 healthy subjects who were volunteers for blood donation and evaluated before and after 450 mL blood donation. Pulsed-wave Doppler of the RV inflow and tissue Doppler of tricuspid lateral annulus, and tricuspid annular plane systolic excursion (TAPSE) were assessed. RESULTS: E velocity of inflow decreased significantly (67.6 +/- 15.9 vs 60.9 +/- 12.2, P = 0.006). S' and A' velocities did not change (15.3 +/- 3.2 vs 15.2 +/- 2.5 cm/s, P = NS; 14.1 +/- 3.3 vs 13.4 +/- 3.1 cm/s, P = NS, respectively) but E' showed significant decrease (13.7 +/- 2.9 vs 12.2 +/- 3.2 cm/s, P = 0.011). E'/A' ratio and E/E' ratio were found to be unchanged (1.0 +/- 0.3 vs 1.0 +/- 0.4, P = NS; 5.1 +/- 2 vs 5.3 +/- 2, P = NS, respectively). Myocardial performance index (MPI) was found to be increased but ejection time obtained from the tricuspid annulus did not change (0.50 +/- 0.13 vs 0.54 +/- 0.11, P = 0.040; 243 +/- 37 vs 240 +/- 27, P = NS, respectively). Isovolumetric relaxation and contraction times showed difference close to the significance limit (56 +/- 19 vs 64 +/- 23 ms, P = 0.055; 61 +/- 16 vs 67 +/- 16 ms, P = 0.062, respectively). TAPSE decreased significantly (2.62 +/- 0.29 vs 2.41 +/- 0.27 mm, P = 0.005). CONCLUSION: E' velocity and TAPSE were sensitive to a volume reduction as little as 450 mL in healthy subjects. MPI index of the tricuspid annulus is less sensitive than E' and TAPSE but need much care under changing volume state. However S' and A' velocity and E'/A' ratio were found to be resistant to the effects of volume depletion. PMID- 22324434 TI - High-performance nanoporous TiO2/La2O3 hybrid photoanode for dye-sensitized solar cells. AB - An organic lanthanum solution was prepared and used for modifying the nanoporous TiO(2) photoanode for dye-sensitized solar cells (DSSCs). The preliminary characterization results demonstrate that La(2)O(3) was formed on the surface of the TiO(2) photoanodes. The X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analyses suggest that La(3+) was introduced into the TiO(2) nanocrystalline, while, the scanning electron microscopy (SEM) and tunnelling electron microscopy (TEM) characterizations suggest that a thin La(2)O(3) layer forms on surface of the TiO(2) nanostructure. The La(2)O(3) layer is able to alleviate the electron recombination as a passivation layer. Though the slight decrease in surface areas were induced by the surface modification, the dye loading were maintained, which can be attributed to the formation of strong co ordination bonding between the dye molecules and the lanthanide. The bonding can also facilitate the electron transfer between the dye molecules and TiO(2) conduction band. Consequently, the open circuit potential and short circuit current were boosted significantly and the overall energy conversion efficiency of the DSSCs was remarkably improved from 6.84% for the control film to 9.67% for the La(3+)-modified film. PMID- 22324435 TI - [5+1] cycloaddition of C,N-cyclic N'-acyl azomethine imines with isocyanides. AB - A catalyst-free [5 + 1] cycloaddition reaction between isocyanides and C,N-cyclic N'-acyl azomethine imines as the "isocyanophile" leading to novel heterocycles has been developed. These reactions proceeded quickly and cleanly to afford the corresponding imin-1,3,4-oxadiazin-6-one derivatives in high to excellent yields. A wide range of C,N-cyclic N'-acyl azomethine imines and isocyanides were applicable to this reaction. PMID- 22324436 TI - Trochlear myokymia secondary to cerebellopontine angle arachnoid cyst. AB - Superior oblique myokymia (SOM) is a rare disorder with an unclear pathogenesis. We describe a first reported case of chronic disabling SOM in association with a cerebellopontine angle arachnoid cyst, who had a gradual and eventually complete symptomatic resolution 8 months following cyst marsupialisation. Among other aetiologies, SOM may therefore be due to abnormal CSF flow dynamics resulting in structural compromise of the nerve. PMID- 22324437 TI - Endoscopic skull base surgery: a comprehensive comparison with open transcranial approaches. AB - Little data exists comparing endoscopic endonasal approaches to pathology of the anterior skull base with more traditional transcranial and transsphenoidal microscopic approaches. In order to more fully characterize the role of endoscopy in the management of pathology of the anterior cranial base, we conducted a systematic review of case series and case reports documenting surgical and clinical outcomes. We found that for craniopharyngiomas, clival chordomas, esthesioneuroblastomas and giant pituitary adenomas, the endonasal endoscopic approach can result in equivalent or higher rates of gross total resection than open approaches. For meningiomas, however, open transcranial approaches are still able to achieve higher rates of total resection. CSF leak rates are higher for patients undergoing endoscopic surgery for meningiomas and craniopharyngiomas, but not for chordomas, esthesioneuroblastomas or giant pituitary adenomas. In certain patients, the endonasal endoscopic approach may be a safe and effective alternative for the treatment of a wide variety of skull base pathology, particularly those with small midline tumours. PMID- 22324438 TI - A meta-analysis to determine the effect of anticoagulation on mortality in patients with blunt head trauma. AB - INTRODUCTION: Patients on warfarin are increasingly common in an ageing population. Previously published case series and cohort studies have resulted in conflicting conclusions with regard to the risk of fatal intracranial haemorrhage. The aim of this study was to undertake a meta-analysis in order to compare the mortality rate of anticoagulated head injured patients against the mortality rate of head injured patients not on coumarin anticoagulation. METHODS: The databases Medline and EMBASE were searched via the ovid interface. The initial search strategy returned 364 results. A second search was performed using Pubmed to identify possible abstracts missed by the first search. Forty-seven full articles were reviewed if the abstract suggested that they were either case control studies or nested case control studies comparing the mortality rate of anticoagulated head injured patients against the mortality rate of head injured patients not on coumarin anticoagulation. RESULTS: Eleven papers were identified, which met the criteria for the meta-analysis. Despite the heterogeneity between the studies (Q test: 27.421, 10 DF, P = 0.002), the fixed effects model may be the preferred model based on the fact that 10 out of the 11 studies had an odds ratio greater than one. The fixed effects model produced a common odds ratio for death in anticoagulated patients with blunt head trauma of 2.008 (95% CI 1.634 - 2.467). CONCLUSIONS: The results of this meta-analysis has shown that the cohort of patients who are anticoagulated and suffer blunt head trauma appear to have an increased risk of death compared to a similar cohort of head injured patients who are not anticoagulated. PMID- 22324439 TI - Silver nanoparticles: the powerful nanoweapon against multidrug-resistant bacteria. AB - In the present scenario, pharmaceutical and biomedical sectors are facing the challenges of continuous increase in the multidrug-resistant (MDR) human pathogenic microbes. Re-emergence of MDR microbes is facilitated by drug and/or antibiotic resistance, which is acquired way of microbes for their survival and multiplication in uncomfortable environments. MDR bacterial infections lead to significant increase in mortality, morbidity and cost of prolonged treatments. Therefore, development, modification or searching the antimicrobial compounds having bactericidal potential against MDR bacteria is a priority area of research. Silver in the form of various compounds and bhasmas have been used in Ayurveda to treat several bacterial infections since time immemorial. As several pathogenic bacteria are developing antibiotic resistance, silver nanoparticles are the new hope to treat them. This review discusses the bactericidal potential of silver nanoparticles against the MDR bacteria. This multiactional nanoweapon can be used for the treatment and prevention of drug-resistant microbes. PMID- 22324440 TI - Pref-1 in brown adipose tissue: specific involvement in brown adipocyte differentiation and regulatory role of C/EBPdelta. AB - Pref-1 (pre-adipocyte factor-1) is known to play a central role in regulating white adipocyte differentiation, but the role of Pref-1 in BAT (brown adipose tissue) has not been analysed. In the present study we found that Pref-1 expression is high in fetal BAT and declines progressively after birth. However, Pref-1-null mice showed unaltered fetal development of BAT, but exhibited signs of over-activation of BAT thermogenesis in the post-natal period. In C/EBP (CCAAT/enhancer-binding protein) alpha-null mice, a rodent model of impaired fetal BAT differentiation, Pref-1 was dramatically overexpressed, in association with reduced expression of the Ucp1 (uncoupling protein 1) gene, a BAT-specific marker of thermogenic differentiation. In brown adipocyte cell culture models, Pref-1 was mostly expressed in pre-adipocytes and declined with brown adipocyte differentiation. The transcription factor C/EBPdelta activated the Pref-1 gene transcription in brown adipocytes, through binding to the proximal promoter region. Accordingly, siRNA (small interfering RNA)-induced C/EBPdelta knockdown led to reduced Pref-1 gene expression. This effect is consistent with the observed overexpression of C/EBPdelta in C/EBPalpha-null BAT and high expression of C/EBPdelta in brown pre-adipocytes. Dexamethasone treatment of brown pre adipocytes suppressed Pref-1 down-regulation occurring throughout the brown adipocyte differentiation process, increased the expression of C/EBPdelta and strongly impaired expression of the thermogenic markers UCP1 and PGC-1alpha [PPARgamma (peroxisome-proliferator-activated receptor gamma) co-activator alpha]. However, it did not alter normal fat accumulation or expression of non BAT-specific genes. Collectively, these results specifically implicate Pref-1 in controlling the thermogenic gene expression program in BAT, and identify C/EBPdelta as a novel transcriptional regulator of Pref-1 gene expression that may be related to the specific role of glucocorticoids in BAT differentiation. PMID- 22324441 TI - Investigation of protective effects of sodium hyaluronate eyedrop against corneal epithelial disorders using an electrophysiological method. AB - PURPOSE: The purpose of this study was to investigate the protective effects of sodium hyaluronate eyedrop against corneal epithelial disorders caused by antiglaucomatous eyedrops using an electrophysiological method. METHODS: Three kinds of antiglaucomatous eyedrops, including benzalkonium chloride (BAC) as an ophthalmic preservative, a BAC-free antiglaucomatous eyedrop, and a sodium hyaluronate eyedrop, were used in this study. Eyedrops were applied to excised rabbit corneas, and the electrophysiological property of the cornea was monitored using an Ussing chamber with a turnover system that mimics human tear turnover. With this system, changes in transepithelial electrical resistance (TER) in the corneal surface were recorded. RESULTS: The corneal TER after applying antiglaucomatous eyedrops tended to decrease concomitantly with increasing the concentration of the BAC included as a preservative. On the other hand, there was no significant change in the corneal TER for the initial 60 min after applying sodium hyaluronate eyedrop compared with those of the control. Moreover, the pretreatment with a sodium hyaluronate eyedrop reduced the extent of decrease in the corneal TER observed after application of antiglaucomatous eyedrops alone. CONCLUSION: Those results indicate that a sodium hyaluronate eyedrop has the potential to protect the corneal surface from antiglaucomatous eyedrops, including BAC as an ophthalmic preservative. PMID- 22324443 TI - Association between oral bisphosphonate use and dental implant failure among middle-aged women. AB - AIM: To investigate the association between the use of oral bisphosphonate therapy and dental implant failure. MATERIALS AND METHODS: The case-control study involved 337 female patients, aged 40 years and older, who had 1181 implants placed at the Department of Periodontology and Implant Dentistry at New York University College of Dentistry between January 1997 and December 2004. Cases, defined as women with one or more implant failures, were identified from the departmental database. Controls were then randomly selected for each case. Adjusted odds ratios were estimated using logistic regression models fitted through generalized estimating equations. RESULTS: After adjusting for selected covariates, the odds of oral bisphosphonate use was 2.69 (95% confidence interval [CI], 1.49-4.86) times higher in women for whom implants failed compared with those for whom implants did not fail. Although no significant interaction was observed (p = 0.41), the stratified analyses suggest that the association between oral bisphosphonate use and dental implant failure was stronger in the maxilla (Odds Ratio [OR] = 2.60; 95% CI, 1.36-4.96) than in the mandible (OR = 1.38; 95% CI, 0.51-3.73). CONCLUSION: Findings from this study suggest that dental practitioners should be aware of the increased risk of implant failure associated with oral bisphosphonate use in the population. PMID- 22324444 TI - Spatiotemporal patterns and ecophysiology of toxigenic microcystis blooms in Lake Taihu, China: implications for water quality management. AB - Whole lake monitoring of hypertrophic Lake Taihu, China, was conducted during the summers of 2009-2010, with the intent of identifying environmental factors influencing Microcystis bloom formation and promoting the growth of toxigenic strains (mcyE possessing). Low N:P ratios (replete N & P)appeared to select for toxigenic populations of Microcystis spp., whereas nontoxic Microcystis spp. strains were dominant in more nutrient limited regions of the lake. Chlorophyll a (Adj. R(2) = 0.83, p < 0.0001) was equally predicative of microcystin variance across the lake as fluorescence based real-time quantitative PCR (qPCR) measurements of microcystin synthetase E (mcyE) gene equivalents (Adj. R(2) = 0.85, p < 0.0001). Interestingly, chlorophyll a was identified as a more robust and useful metric for predicting microcystin concentrations than qPCR measurements enumerating the total Microcystis population based on c-phycocyanin (alpha subunit; cpcA) gene equivalents (Adj. R(2) = 0.61, p < 0.0001). Overall, the lakewide composition of Microcystis spp. was highly variable over time and space, and on average the population consisted of 36 +/- 12% potentially toxic cells. On the basis of this study's findings, a framework for the design and implementation of a water safety plan for Taihu water quality managers and public health officials is proposed. PMID- 22324445 TI - AMPK activator AICAR ameliorates ischaemia reperfusion injury in the rat kidney. AB - BACKGROUND AND PURPOSE Renal ischaemia/reperfusion (RI/R) injury is a major cause of acute kidney injury (AKI) and an important determinant of long-term kidney dysfunction. AMP-kinase and histone deacetylase sirtuin 1 (SIRT1) regulate cellular metabolism and are activated during hypoxia. We investigated whether AMP kinase activator AICAR (5-amino-4-imidazolecarboxamide riboside-1-beta-D ribofuranoside) ameliorates RI/R injury and whether SIRT1 is involved in the pathogenesis. EXPERIMENTAL APPROACH Eight-week-old Sprague Dawley rats were divided into five groups: (i) sham-operated group; (ii) I/R group (40 min bilateral ischaemia followed by 24 h of reperfusion; (iii) I/R group + AICAR 50 mg.kg(-1) i.v. given 60 min before operation; (iv). I/R group + AICAR 160 mg.kg( 1) i.v; (v) I/R group + AICAR 500 mg.kg(-1) i.v. Serum creatinine and urea levels were measured. Acute tubular necrosis (ATN), monocyte/macrophage infiltration and nitrotyrosine expression were scored. Kidney AMP-activated protein kinase (AMPK) and SIRT1 expressions were measured. KEY RESULTS Highest dose of AICAR decreased serum creatinine and urea levels, attenuated I/R injury-induced nitrosative stress and monocyte/macrophage infiltration, and ameliorated the development of ATN. Kidney I/R injury was associated with decreased AMPK phosphorylation and a fivefold increase in kidney SIRT1 expression. AICAR increased pAMPK/AMPK ratio and prevented the I/R-induced increase in renal SIRT1 expression. CONCLUSIONS AND IMPLICATIONS AICAR protects against the development of ATN after kidney I/R injury. Activators of kidney AMP kinase may thus represent a novel therapeutic approach to patients susceptible to AKI and to those undergoing kidney transplantation. The present study also suggests a role for SIRT1 in the pathogenesis of RI/R injury. PMID- 22324446 TI - Community-based study of health-related quality of life in spinal cord injury, muscular dystrophy, multiple sclerosis, and cerebral palsy. AB - PURPOSE: To assess health-related quality of life (HRQOL) in adults with spinal cord injury (SCI), muscular dystrophy (MD), multiple sclerosis (MS), and cerebral palsy (CP). METHODS: This is a multicenter, community-based, cross-sectional study of adults diagnosed with CP (94), MD (99), MS (98), SCI (99), and healthy adults (105). The WHOQOL-BREF and WHOQOL-DIS questionnaire were used. RESULTS: Significant differences in physical functioning between adults with CP and SCI and adults with MS (p = 0.003 and p < 0.001, respectively), as well as between adults with SCI and MD (p = 0.001) were found. Univariate tests revealed significant psychological functioning differences between adults with SCI and MD (p = 0.02) and SCI and MS (p = 0.001). There was a significant difference in physical functioning between controls and adults with SCI (p = 0.049) and a significant difference in psychological functioning between controls and adults with MS (p = 0.039). No statistically significant differences were found between the groups in social and environmental domains. CONCLUSIONS: Physical and physiological functioning were affected to various degrees in the studied neurodisabilities, while all groups reported similar levels of functioning and well-being in social and environmental domains. PMID- 22324447 TI - Simultaneous conduction of electronic charge and lithium ions in block copolymers. AB - The main objective of this work is to study charge transport in mixtures of poly(3-hexylthiophene)-b-poly(ethylene oxide) (P3HT-PEO) block copolymers and lithium bis(trifluoromethanesulfonyl) imide salt (LiTFSI). The P3HT-rich microphase conducts electronic charge, while the PEO-rich microphase conducts ionic charge. The nearly symmetric P3HT-PEO copolymer used in this study self assembles into a lamellar phase. In contrast, the morphologies of asymmetric copolymers with P3HT as the major component are dominated by nanofibrils. A combination of ac and dc impedance measurements was used to determine the electronic and ionic conductivities of our samples. The ionic conductivities of P3HT-PEO/LiTFSI mixtures are lower than those of mixtures of PEO homopolymer and LiTFSI, in agreement with published data obtained from other block copolymer/salt mixtures. In contrast, the electronic conductivities of the asymmetric P3HT-PEO copolymers are significantly higher than those of the P3HT homopolymer. This is unexpected because of the presence of the nonelectronically conducting PEO microphase. This implies that the intrinsic electronic conductivity of the P3HT microphase in P3HT-PEO copolymers is significantly higher than that of P3HT homopolymers. PMID- 22324448 TI - Randomised clinical trial: efficacy of a new synbiotic formulation containing Lactobacillus paracasei B21060 plus arabinogalactan and xilooligosaccharides in children with acute diarrhoea. AB - BACKGROUND: Acute diarrhoea is a frequent problem in children with heavy economic burden for families and society. AIM: To test the efficacy of a new synbiotic formulation containing Lactobacillus paracasei B21060, arabinogalactan and xilooligosaccharides in children with acute diarrhoea. METHODS: Double-blind, randomised, placebo-controlled trial, including children (age 3-36 m) with acute diarrhoea who were allocated to placebo or synbiotic group. Major outcome was resolution rate of diarrhoea at 72 h. Total duration of diarrhoea, daily stool outputs, stool consistency, working days lost by parents, adjunctive medications, and hospitalisation were also assessed. RESULTS: We enrolled 55 children in placebo group and 52 in synbiotic group. The two groups were similar for demographic and clinical characteristics. Resolution rate of diarrhoea at 72 h was significantly higher in synbiotic group (67%) compared to placebo group (40%, P = 0.005). Children in synbiotic group showed a significant reduction in the duration of diarrhoea (90.5 h, 78.1-102.9 vs. 109.8 h, 96.0-123.5, P = 0.040), daily stool outputs (3.3, 2.8-3.8 vs. 2.4, 1.9-2.8, P = 0.005) and stool consistency (1.3, 0.9-1.6 vs. 0.6, 0.4-0.9, P = 0.002) compared to placebo group (data expressed as mean, 95% CI). Rate of parents that missed at least one working day (41.8% vs. 15.4%, P = 0.003), rate of children that needed adjunctive medications (25.5% vs. 5.8%, P = 0.005) or hospitalisation (10.9% vs. 0%, P = 0.014) after the first 72 h of treatment, were reduced in synbiotic group. CONCLUSION: The synbiotic formulation studied is effective in children with acute diarrhoea. Australian New Zealand Clinical Trials Registry (ACTRN12611000641998). PMID- 22324449 TI - Transcriptome analysis and gene expression atlas for Panicum hallii var. filipes, a diploid model for biofuel research. AB - Panicum hallii is an emerging model for genetic studies of agronomic traits in Panicum, presenting a tractable diploid alternative study system to the tetra- or octaploid biofuel crop switchgrass (Panicum virgatum). To characterize the gene complement in P. hallii var. filipes and enable gene expression analysis in this system we sequenced, assembled, and annotated the transcriptome. Over 300 Mb of normalized cDNA prepared from multiple tissues and treatments was sequenced using 454-Titanium, producing an annotated assembly including 15 422 unique gene names. Comparison with other grass genomes identified putative P. hallii homologs for >14 000 previously characterized genes. We also developed an atlas of gene expression across tissues and stages using RNA-Seq (the quantitative analysis of short cDNA reads). SOLiD sequencing and quantitative analysis of more than 40 million cDNA tags identified substantial variation in expression profiles among tissues, consistent with known functional differences. Putative homologs were found for all enzymes in the phenylpropanoid pathway leading to lignin biosynthesis, including genes with known effects on biomass conversion efficiency. The resources developed here will enable studies of the genes underlying variation in cell wall composition, drought tolerance, and biomass production in Panicum. PMID- 22324450 TI - Optimization and validation of the reversed-phase high-performance liquid chromatography with fluorescence detection method for the separation of tocopherol and tocotrienol isomers in cereals, employing a novel sorbent material. AB - The separation and determination of tocopherols (Ts) and tocotrienols (T3s) by reversed-phase high-performance liquid chromatography with fluorescence detection has been developed and validated after optimization of various chromatographic conditions and other experimental parameters. Analytes were separated on a PerfectSil Target ODS-3 (250 * 4.6 mm, 3 MUm) column filled with a novel sorbent material of ultrapure silica gel. The separation of Ts and T3s was optimized in terms of mobile-phase composition and column temperature on the basis of the best compromise among efficiency, resolution, and analysis time. Using a gradient elution of mobile phase composed of isopropanol/water and 7 degrees C column temperature, a satisfactory resolution was achieved within 62 min. For the quantitative determination, alpha-T acetate (50 MUg/mL) was used as the internal standard. Detection limits ranged from 0.27 MUg/mL (gamma-T) to 0.76 MUg/mL (gamma-T3). The validation of the method was examined performing intraday (n = 5) and interday (n = 3) assays and was found to be satisfactory, with high accuracy and precision results. Solid-phase extraction provided high relative extraction recoveries from cereal samples: 87.0% for gamma-T3 and 115.5% for delta-T. The method was successfully applied to cereals, such as durum wheat, bread wheat, rice, barley, oat, rye, and corn. PMID- 22324451 TI - Left atrial size and function are related to pulmonary hypertension in coronary artery disease. AB - BACKGROUND: Left atrial (LA) size reflects diastolic burden and is a prognostic parameter of common cardiovascular death. However, the association between LA size and function and pulmonary hypertension (PH) in coronary artery disease (CAD) has not been well investigated. We hypothesized that LA size and function are associated with PH in CAD. METHODS: One hundred seven patients with CAD were studied. LA size was determined in three different methods; namely, LA volume index (LAV), LA area index, and LA dimension. LAV total emptying fraction was also determined. Pulsed Doppler E, A, E/A, DT, tissue Doppler E', A', and E/E' were measured. Pulmonary artery systolic pressure (PASP) was estimated. RESULTS: All LA size parameters are significantly associated with PH. LAV emptying fraction, age, E, E/A, E/E', and A' were also associated with PH significantly. CAD patients with PH showed larger LA size, higher E, E/A, and E/E' and lower LAV emptying fraction, A and A' than CAD patients without PH. Multivariate regression analysis revealed that maximum LAV, E, E/A ratio, and age were independent predictors of PH. Maximum LAV > 35.6 mL/m(2) predicted PASP > 40 mmHg with a sensitivity of 83.9% and specificity of 62.2%. CONCLUSION: LAV is associated with PH in CAD patients. PMID- 22324452 TI - Alcohol-dependence: the current French craze for baclofen. PMID- 22324453 TI - Total synthesis of (+)-cyperolone. AB - The total synthesis of (+)-cyperolone, an eudesmane-derived sesquiterpenoid from Cyperus rotundus, is described. The de novo synthesis was accomplished via a 15 step sequence starting from (R)-(-)-carvone. The synthetic route features a platinum-catalyzed cycloisomerization to rapidly construct the bicyclic core from a 3-silyloxy-1,5-enyne intermediate. PMID- 22324454 TI - pH- and glucose-responsive core-shell hybrid nanoparticles with controllable metal-enhanced fluorescence effects. AB - In this paper, a novel core-shell hybrid nanoparticle with a silver core and cross-linked poly(3-acrylamidephenylboronic acid-co-acrylic acid) shell (Ag@PAPBA PAA) was reported. The prepared hybrid nanoparticles can exhibit good responsiveness to the glucose concentration and pH of the environment and exhibit a responsive swelling and shrinking behavior. Tuned by the glucose concentration or pH, a swelling of up to 15.0 nm thickness of the hybrid nanoparticle shell can be observed. These unique responsive properties can be employed to tune the metal enhanced fluorescence (MEF) effects of the incorporated Ag cores. The fluorescence of adsorbed positively charged porphyrin molecules (Por(4+)) shows good sensitivity to the glucose concentration and pH with an enhancement of up to about 1.8-fold. These functional hybrid nanoparticles with tunable MEF effects show a great potential application in the fields of responsive fluorescent sensing and detection. PMID- 22324455 TI - Genetic diversity among VRE isolates from Swedish broilers with the coincidental finding of transferrable decreased susceptibility to narasin. AB - AIMS: In this study, the molecular diversity among clones of vancomycin resistant Enterococcus faecium with vanA gene (VRE) is investigated. The aims were to better understand why one clone is predominant in Swedish broiler production and to better assess the potential for zoonotic gene transfer from the different clones. METHODS AND RESULTS: Twenty-six isolates were separated into 11 clones. Vancomycin resistance was transferrable from the predominant and five minority clones. Decreased susceptibility to narasin was co-transferred with vancomycin resistance in four clones, including the predominant. The plasmid addiction system axe-txe was not detected, and the omega-epsilon-zeta system was detected in one of the minority clones but was not co-transferred with vancomycin resistance. CONCLUSIONS: The results do not explain why one clone is predominant among VRE in Swedish broiler production but confirms the potential for zoonotic spread of vancomycin resistance genes. The near absence of investigated plasmid addiction systems indicates that they do not play an important role in the epidemiology of VRE in Swedish broiler production. The finding that decreased susceptibility to narasin can be co-transferred with the vanA gene indicates that the use of narasin might play a role in the persistence of vancomycin resistance in enterococci colonizing Swedish broilers. SIGNIFICANCE AND IMPACT OF THE STUDY: This is, to our knowledge, the first report of transferrable decreased susceptibility to narasin. PMID- 22324456 TI - Histological results after maxillary sinus augmentation with Straumann(r) BoneCeramic, Bio-Oss(r), Puros(r), and autologous bone. A randomized controlled clinical trial. AB - OBJECTIVE: This investigation focused on a comparison of clinical and histological characteristics after sinus floor augmentation with biphasic calcium phosphate (BCP, Straumann BoneCeramic((r)) ), anorganic bovine bone (ABB, Geistlich Bio-Oss((r)) ), mineralized cancellous bone allograft (MCBA, Zimmer Puros((r)) ), or autologous bone (AB). MATERIALS AND METHODS: Thirty consecutive patients with a posterior edentulous maxillary situation and a vertical bone height less than or equal to 4 mm were included in this study. A two-stage procedure was carried out. After augmentation of the maxillary sinus with ABB, BCP, MCBA, or AB followed by a healing period of 5 months, biopsies were taken with simultaneous implant placement. The samples were analyzed using microradiography and histology. RESULTS: Ninety-four implants were placed in the augmented positions and 53 bone biopsies were taken and evaluated. The bone volume fraction of newly formed bone was measured as 30.28 +/- 2.16% for BCP, 24.9 +/- 5.67% for ABB, 41.74 +/- 2.1% for AB, and 35.41 +/- 2.78% for MCBA with significant increases in bone volume of AB vs. BCP and ABB, and MCBA vs. ABB samples. Significantly different residual bone substitute material was measured as 15.8 +/- 2.1% in the BCP group and 21.36 +/- 4.83% in the ABB group. CONCLUSION: As it provides the highest rate of de novo bone formation, AB can be considered to remain the gold standard in sinus floor augmentation. All tested control materials showed comparable results and are suitable for maxillary sinus augmentation. PMID- 22324457 TI - Providing the missing link: the exposure science ontology ExO. AB - Environmental health information resources lack exposure data required to translate molecular insights, elucidate environmental contributions to diseases, and assess human health and ecological risks. We report development of an Exposure Ontology, ExO, designed to address this information gap by facilitating centralization and integration of exposure data. Major concepts were defined and the ontology drafted and evaluated by a working group of exposure scientists and other ontology and database experts. The resulting major concepts forming the basis for the ontology are "exposure stressor", "exposure receptor", "exposure event", and "exposure outcome". Although design of the first version of ExO focused on human exposure to chemicals, we anticipate expansion by the scientific community to address exposures of human and ecological receptors to the full suite of environmental stressors. Like other widely used ontologies, ExO is intended to link exposure science and diverse environmental health disciplines including toxicology, epidemiology, disease surveillance, and epigenetics. PMID- 22324458 TI - Systematic screening for urinary incontinence in older women: who could benefit from it? AB - OBJECTIVE: To identify women who are suffering from urinary incontinence but do not consult a physician and to identify reasons for this. DESIGN: Survey study as part of a randomized controlled trial that investigates the effects of a standardized assessment and evidence-based treatment on urinary incontinence in older women, the URINO project. SETTING: Female patients from general practices in the Northern part of the Netherlands. PATIENTS: A total of 225 women of 55 years and older suffering from urinary incontinence. MAIN OUTCOME MEASURES: Number of patients with urinary incontinence who are not registered by their GP as suffering from this, factors associated with help-seeking behaviour, and reasons for not seeking help. RESULTS: Of the 225 patients, 143 (64%) were not registered by their GP as suffering from urinary incontinence. These women were more often younger and had lower levels of distress due to their urogynaecological symptoms. The most common reason for not consulting a GP was that patients considered their symptoms not to be serious enough. CONCLUSION: The prevalence of older women with urinary incontinence who do not seek help is high. Help-seeking behaviour is associated with increasing age and higher levels of distress caused by the symptoms. Younger patients more often hesitate to consult their GP if they perceive their symptoms to be relatively mild. PMID- 22324459 TI - Study of interaction energies between the PAMAM dendrimer and nonsteroidal anti inflammatory drug using a distributed computational strategy and experimental analysis by ESI-MS/MS. AB - The structure of a dendrimer exhibits a large number of internal and superficial cavities, which can be exploited, to capture and deliver small organic molecules, enabling their use in drug delivery. Structure-based modeling and quantum mechanical studies can be used to accurately understand the interactions between functionalized dendrimers and molecules of pharmaceutical and industrial interest. In this study, we implemented a Metropolis Monte Carlo algorithm to calculate the interaction energy of dendrimer-drug complexes, which can be used for in silico prediction of dendrimer-drug affinity. Initially, a large-scale sampling of different dendrimer-drug conformations was generated using Euler angles. Then, each conformation was distributed on different nodes of a GRID computational system, where its interaction energy was calculated by semiempirical quantum mechanical methods. These energy calculations were performed for four different nonsteroidal anti-inflammatory drugs, each showing different affinities for the PAMAM-G4 dendrimer. The affinities were also characterized experimentally by using Cooks' kinetic method to calculate PAMAM drug dissociation constants. The quantitative structure-activity relationship between the interaction energies and dissociation constants showed statistical correlations with r(2) > 0.9. PMID- 22324460 TI - A cost-minimization analysis of root canal treatment before and after education in nickel-titanium rotary technique in general practice. AB - AIM: To compare root canal treatments performed before and after education in a nickel-titanium rotary technique (NiTiR) with respect to costs for instrumentation and number of instrumentation sessions in a County Public Dental Service in Sweden. METHODOLOGY: Following education, 77% of the general dental practitioners adopted completely the NiTiR. The randomly selected sample comprised 850 root canal treatments: 425 performed after the education, mainly using the NiTiR-technique (group A) and 425 performed before, using mainly stainless steel hand instrumentation (SSI) (group B). The number of instrumentation sessions in root canal treatments in group A and B was calculated. A CMA was undertaken on the assumption that treatment outcome was identical in group A and B. Direct costs associated with SSI and NiTiR were estimated and compared. Investment costs required for implementation of NiTiR were calculated, but not included in the CMA. RESULTS: Instrumentation sessions were counted in 418 (98%) root canal treatments performed in group A and 419 (99%) in group B. The number of instrumentation sessions in group A was significantly lower; 2.38, compared with 2.82 in group B (P < 0.001). Thus, on average, for every second root canal treatment performed after the education, one instrumentation session was saved. Root canal treatments in teeth with one canal, and three or more canals, were completed in significantly fewer instrumentation sessions after the education (P < 0.001). Direct costs of instrumentation sessions were SEK 2587 (USD 411) for group A and SEK 2851 (USD 453) for group B, for teeth with one canal, and SEK 2946 (USD 468) for group A and SEK 3510 (USD 558) for group B, for teeth with three or more canals (year 2011). Root canal treatments of teeth with two canals showed no significant difference with respect to number of instrumentation sessions and costs. CONCLUSIONS: Significantly fewer instrumentation sessions were required in group A, and root canal instrumentation therefore costs less than in group B. On the assumption that treatment outcome is identical in group A and B, root canal instrumentation performed after the education was more cost-effective. PMID- 22324461 TI - Mechanisms of replication fork protection: a safeguard for genome stability. AB - During S-phase, the genome is extremely vulnerable and the progression of replication forks is often threatened by exogenous and endogenous challenges. When replication fork progression is halted, the intra S-phase checkpoint is activated to promote structural stability of stalled forks, preventing the dissociation of replisome components. This ensures the rapid resumption of replication following DNA repair. Failure in protecting and/or restarting the stalled forks contributes to alterations of the genome. Several human genetic diseases coupled to an increased cancer predisposition are caused by mutations in genes involved in safeguarding genome integrity during DNA replication. Both the ATR (ataxia telangiectasia and Rad3-related protein) kinase and the Replication pausing complex (RPC) components Tipin, Tim1 and Claspin play key roles in activating the intra S-phase checkpoint and in stabilizing the stalled replication forks. Here, we discuss the specific contribution of these factors in preserving fork structure and ensuring accurate completion of DNA replication. PMID- 22324463 TI - Roles of nucleation, denucleation, coarsening, and aggregation kinetics in nanoparticle preparations and neurological disease. AB - Kinetic models for nucleation, denucleation, Ostwald ripening (OR), and nanoparticle (NP) aggregation are presented and discussed from a physicochemical standpoint, in terms of their role in current NP preparations. Each of the four solid-state mechanisms discussed predict a distinct time dependence for the evolution of the mean particle radius over time. Additionally, they each predict visually different particle size distributions (PSDs) under limiting steady-state (time-independent) conditions. While nucleation and denucleation represent phase transformation mechanisms, OR and NP aggregation do not. Thus, when modeling solid-state kinetics relevant to NP processing, either the time evolution of the mean particle radius or the fractional conversion data should be fit using appropriate models (discussed herein), without confusing/combining the two classes of models. Experimental data taken from the recent literature are used to demonstrate the usefulness of the models in real-world applications. Specifically, the following examples are discussed: the preparation of bismuth NPs, the synthesis of copper indium sulfide nanocrystals, and the aggregation of neurological proteins. Because the last process is found to obey reaction-limited colloid aggregation (RLCA) kinetics, potential connections between protein aggregation rates, the onset of neurological disease, and population lifespan dynamics are suggested by drawing a parallel between RLCA kinetics and Gompertz kinetics. The physical chemistry underpinning NP aggregation is investigated, and a detailed definition of the rate constant of aggregation, k(a), is put forth that provides insight into the origin of the activation energy barrier of aggregation. For the two nanocrystal preparations investigated, the initial kinetics are found to be well-described by the author's dispersive kinetic model for nucleation-and-growth, while the late-stage NP size evolution is dominated by OR. At intermediate times, it is thought that the two mechanisms both contribute to the NP growth, resulting in PSD focusing as discussed in a previous work [Skrdla, P. J. J. Phys. Chem. C2012, 116, 214-225]. On the basis of these two mechanisms, a synthetic procedure for obtaining monodisperse NP PSDs, of small and/or systematically targeted mean sizes, is proposed. PMID- 22324464 TI - The use of chronic gingivitis as reference status increases the power and odds of periodontitis genetic studies: a proposal based in the exposure concept and clearer resistance and susceptibility phenotypes definition. AB - AIM: Current literature on chronic periodontitis genetics encompasses numerous single nucleotide polymorphisms-focused case-control studies with inconsistent and controversial results, which typically disregards the exposure concept embraced by case-control definition. Herein, we propose a case-control design reappraisal by clear phenotype selection, where chronic gingivitis represents a genetically resistant phenotype/genotype opposing the susceptible cohort. MATERIAL AND METHODS: The hypothesis was tested in healthy, chronic periodontitis and gingivitis groups through Real-time PCR-based allelic discrimination of classic variants IL1B-3954, IL6-174, TNFA-308, IL10-592 and TLR4-299. RESULTS: Observed allele/genotype frequencies characterize the healthy group with an intermediate genetic profile between periodontitis and gingivitis cohorts. When comparing genotype/allele frequencies in periodontitis versus healthy and periodontitis versus gingivitis scenarios, the number of positive associations (2 4) and the degree of association (p and odds ratio values) were significantly increased by the new approach proposed (periodontitis versus gingivitis), suggesting the association of IL1B-3954, TNFA-308, IL10-592 and TLR4-299 with periodontitis risk. Power study was also significantly improved by the new study design proposed when compared to the traditional approach. CONCLUSIONS: The data presented herein support the use of new case-control study design based on the case-control definition and clear resistance/susceptibility phenotypes selection, which can significantly impact the study power and odds of identification of genetic factors involved in PD. PMID- 22324466 TI - Curcumin inhibits thrombin-stimulated connective tissue growth factor (CTGF/CCN2) production through c-Jun NH2-terminal kinase suppression in human gingival fibroblasts. AB - BACKGROUND: Connective tissue growth factor (CTGF/CCN2), associated with multiple human fibrotic diseases, is overexpressed in the tissue of gingival overgrowth. Although surgical excision is the current treatment modality for gingival overgrowth, the recurrent rate is high despite proper recall programs. Thrombin plays a key role in wound repair, remodeling, and fibrosis after injury and exerts profibrotic effects by activating protease-activated receptors (PARs). Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] is a natural plant phenolic compound that possesses both anti-inflammatory and antioxidant properties. This study investigates the signaling pathway of thrombin induced CCN2 expression and inhibition of CCN2 expression by curcumin. METHODS: The signaling pathway of thrombin-induced CCN2 expression in human gingival fibroblasts (HGFs) was studied using Western blot analysis. The CCN2 mRNA level was determined by quantitative reverse transcription-polymerase chain reaction. RESULTS: Thrombin induced CCN2 expression in HGFs by activating PAR1. Pretreatment with antioxidant N-acetyl-l-cysteine, apoptosis signal-regulating kinase 1 (ASK1) inhibitor thioredoxin, and c-Jun NH2-terminal kinase (JNK) inhibitor SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one) significantly reduced thrombin-induced CCN2 expression in HGFs. Curcumin dose dependently inhibited thrombin-induced CCN2 expression through JNK suppression in HGFs. CONCLUSIONS: The results of this study suggest that thrombin-induced CCN2 expression may occur through PAR1, reactive oxygen species, ASK1, and JNK signaling in HGFs. Curcumin could effectively inhibit CCN2 expression through JNK suppression. These signaling events are important for wound healing and fibrosis. Additional research, including animal studies, is required to confirm the inhibiting role of curcumin in the development of gingival overgrowth. PMID- 22324467 TI - Impact of periodontal therapy on the subgingival microbiota of severe periodontitis: comparison between good responders and individuals with refractory periodontitis using the human oral microbe identification microarray. AB - BACKGROUND: This study compares the changes to the subgingival microbiota of individuals with "refractory" periodontitis (RP) or treatable periodontitis (good responders [GR]) before and after periodontal therapy by using the Human Oral Microbe Identification Microarray (HOMIM) analysis. METHODS: Individuals with chronic periodontitis were classified as RP (n = 17) based on mean attachment loss (AL) and/or >3 sites with AL >=2.5 mm after scaling and root planing, surgery, and systemically administered amoxicillin and metronidazole or as GR (n = 30) based on mean attachment gain and no sites with AL >=2.5 mm after treatment. Subgingival plaque samples were taken at baseline and 15 months after treatment and analyzed for the presence of 300 species by HOMIM analysis. Significant differences in taxa before and post-therapy were sought using the Wilcoxon test. RESULTS: The majority of species evaluated decreased in prevalence in both groups after treatment; however, only a small subset of organisms was significantly affected. Species that increased or persisted in high frequency in RP but were significantly reduced in GR included Bacteroidetes sp., Porphyromonas endodontalis, Porphyromonas gingivalis, Prevotella spp., Tannerella forsythia, Dialister spp., Selenomonas spp., Catonella morbi, Eubacterium spp., Filifactor alocis, Parvimonas micra, Peptostreptococcus sp. OT113, Fusobacterium sp. OT203, Pseudoramibacter alactolyticus, Streptococcus intermedius or Streptococcus constellatus, and Shuttlesworthia satelles. In contrast, Capnocytophaga sputigena, Cardiobacterium hominis, Gemella haemolysans, Haemophilus parainfluenzae, Kingella oralis, Lautropia mirabilis, Neisseria elongata, Rothia dentocariosa, Streptococcus australis, and Veillonella spp. were more associated with therapeutic success. CONCLUSION: Persistence of putative and novel periodontal pathogens, as well as low prevalence of beneficial species was associated with chronic refractory periodontitis. PMID- 22324468 TI - Poor oral health and coronary artery disease: a case-control study. AB - BACKGROUND: There is insufficient research on the relationship of oral health and coronary artery disease (CAD) from developing countries, such as Pakistan. This study observes the status of oral health in the CAD population. METHODS: A case control study was conducted on 145 cases and 145 controls. Otherwise healthy patients with CAD (cases) and individuals free from previous/current history of CAD (controls), having >=14 remaining teeth, were examined for oral health status through missing teeth, plaque index (PI), and community periodontal index (CPI). Student t test, chi2 test, and multivariate regression analysis were applied at significance level of 95% (P <= 0.05) to compare study parameters between cases and controls. RESULTS: A significant difference between cases and controls was observed in this study sample with respect to missing teeth (P = 0.027) and periodontal parameters of PI and CPI (P < 0.001). Cases were observed with significantly higher scores of PI (2 and 3) and CPI (3 and 4) compared with controls. Prevalence of periodontal parameters was observed to be higher in cases than controls at subgroup-level (sex and age group) analysis. A significant odds ratio (OR), unadjusted, between CAD and periodontal indicators of PI (mild to severe plaque/no plaque: OR = 5.04, 95% confidence interval [95% CI] = 2.24 to 11.36) and CPI (healthy/poor periodontal status: OR = 4.59, 95% CI = 1.81 to 11.61) scores was noted; cases were at odds of 1.20 (95% CI = 0.93 to 15.68, P = 0.017) for having poor oral health after adjusting age, sex, and education. CONCLUSION: Poor oral health was significantly associated with CAD in this study sample matched for sociodemographic characteristics. PMID- 22324469 TI - Cyclooxygenase-2 expression in gingival biopsies from periodontal patients is correlated with connective tissue loss. AB - BACKGROUND: The objective of this study is to compare cyclooxygenase-2 (COX-2) protein expression in gingival biopsies from patients with chronic periodontitis (CP), patients with gingivitis (GV), and individuals with no periodontal disease (control group) and to establish its relationship with clinical variables and connective tissue loss in the lamina propria. METHODS: A cross-sectional and analytic study was conducted in 108 gingival biopsies from 52 patients with CP, 39 with GV, and 17 controls. All biopsies were processed for conventional histopathologic study, immunohistochemical determination of COX-2 protein expression, and automatic quantification of connective tissue by image analysis. RESULTS: The protein expression of COX-2, mainly produced by plasma cells and monocytes, was significantly related to the presence of periodontal disease, bleeding index, intensity of inflammatory infiltrate, and loss of connective tissue in the lamina propria of gingival biopsies (P <0.01, Spearman test). COX-2 expression was also directly correlated with attachment loss (P <0.05, Spearman test). CONCLUSIONS: COX-2 protein expression is higher in patients with GV and CP than in individuals without periodontal disease and is inversely correlated with the amount of connective tissue in the lamina propria as determined by image analysis. This finding suggests that COX-2 participates in mechanisms and pathway signaling related to the destruction of fibrillar support structures of the periodontium. PMID- 22324470 TI - IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential. AB - IL-17 (interleukin-17), a hallmark cytokine of Th17 (T-helper 17) cells, plays critical roles in host defence against bacterial and fungal infections, as well as in the pathogenesis of autoimmune diseases. The present review focuses on current knowledge of the regulation, functional mechanisms and targeting strategies of IL-17 in the context of inflammatory autoimmune diseases. Evidence shows that IL-17 is highly up-regulated at sites of inflammatory tissues of autoimmune diseases and amplifies the inflammation through synergy with other cytokines, such as TNF (tumour necrosis factor) alpha. Although IL-17 was originally thought to be produced mainly by Th17 cells, a newly defined T-cell subset with a specific differentiation programme and tight regulation, several other cell types (especially innate immune cells) are also found as important sources for IL-17 production. Although IL-17 activates common downstream signalling, including NF-kappaB (nuclear factor kappaB), MAPKs (mitogen-activated protein kinases), C/EBPs (CCAAT/enhancer-binding proteins) and mRNA stability, the immediate receptor signalling has been shown to be quite unique and tightly regulated. Mouse genetic studies have demonstrated a critical role for IL-17 in the pathogenesis of variety of inflammatory autoimmune diseases, such as RA (rheumatoid arthritis) and MS (multiple sclerosis). Importantly, promising results have been shown in initial clinical trials of monoclonal antibodies against IL-17 or its receptor (IL-17R) to block IL-17-mediated function in treating autoimmune patients with psoriasis, RA and MS. Therefore targeting IL 17/IL-17R, IL-17-producing pathways or IL-17-mediated signalling pathways can be considered for future therapy in autoimmune diseases. PMID- 22324471 TI - Inhibition of soluble epoxide hydrolase by cis-4-[4-(3-adamantan-1 ylureido)cyclohexyl-oxy]benzoic acid exhibits antihypertensive and cardioprotective actions in transgenic rats with angiotensin II-dependent hypertension. AB - The present study was undertaken to evaluate the effects of chronic treatment with c-AUCB {cis-4-[4-(3-adamantan-1-ylureido)cyclohexyl-oxy]benzoic acid}, a novel inhibitor of sEH (soluble epoxide hydrolase), which is responsible for the conversion of biologically active EETs (epoxyeicosatrienoic acids) into biologically inactive DHETEs (dihydroxyeicosatrienoic acids), on BP (blood pressure) and myocardial infarct size in male heterozygous TGR (Ren-2 renin transgenic rats) with established hypertension. Normotensive HanSD (Hannover Sprague-Dawley) rats served as controls. Myocardial ischaemia was induced by coronary artery occlusion. Systolic BP was measured in conscious animals by tail plethysmography. c-AUCB was administrated in drinking water. Renal and myocardial concentrations of EETs and DHETEs served as markers of internal production of epoxygenase metabolites. Chronic treatment with c-AUCB, which resulted in significant increases in the availability of biologically active epoxygenase metabolites in TGR (assessed as the ratio of EETs to DHETEs), was accompanied by a significant reduction in BP and a significantly reduced infarct size in TGR as compared with untreated TGR. The cardioprotective action of c-AUCB treatment was completely prevented by acute administration of a selective EETs antagonist [14,15-epoxyeicosa-5(Z)-enoic acid], supporting the notion that the improved cardiac ischaemic tolerance conferred by sEH inhibition is mediated by EETs actions at the cellular level. These findings indicate that chronic inhibition of sEH exhibits antihypertensive and cardioprotective actions in this transgenic model of angiotensin II-dependent hypertension. PMID- 22324472 TI - Agonist-dependent modulation of arterial endothelinA receptor function. AB - BACKGROUND AND PURPOSE Endothelin-1 (ET-1) causes long-lasting vasoconstrictions. These can be prevented by ET(A) receptor antagonists but are only poorly reversed by these drugs. We tested the hypothesis that endothelin ET(A) receptors are susceptible to allosteric modulation by endogenous agonists and exogenous ligands. EXPERIMENTAL APPROACH Rat isolated mesenteric resistance arteries were pretreated with capsaicin and studied in wire myographs, in the presence of L NAME and indomethacin to concentrate on arterial smooth muscle responses. KEY RESULTS Endothelins caused contractions with equal maximum but differing potency (ET-1 = ET-2 > ET-3). ET-1(1-15) neither mimicked nor antagonized these effects in the absence and presence of ET(16-21). 4(Ala) ET-1 (ET(B) agonist) and BQ788 (ET(B) antagonist) were without effects. BQ123 (peptide ET(A) antagonist) reduced the sensitivity and relaxed the contractile responses to endothelins. Both effects depended on the agonist (pK(B): ET-3 = ET-1 > ET-2; % relaxation: ET-3 = ET-2 > ET-1). Also, with PD156707 (non-peptide ET(A) antagonist) agonist dependence and a discrepancy between preventive and inhibitory effects were observed. The latter was even more marked with bulky analogues of BQ123 and PD156707. CONCLUSIONS AND IMPLICATIONS These findings indicate allosteric modulation of arterial smooth muscle ET(A) receptor function by endogenous agonists and by exogenous endothelin receptor antagonists. This may have consequences for the diagnosis and pharmacotherapy of diseases involving endothelins. PMID- 22324473 TI - Effects of a repetitive gaming intervention on upper extremity impairments and function in persons with chronic stroke: a preliminary study. AB - PURPOSE: The purpose of this study was to examine the feasibility and effects of an upper extremity gaming system on impairments, activity and participation restrictions in persons with chronic stroke. METHOD: Nine participants with chronic (5.4 SD 3 years after stroke) upper extremity impairment due to stroke completed 18 sessions over 6 weeks with the Hand Dance ProTM gaming system that included trunk restraint. Measures collected at pretest and posttest included three-dimensional motion analysis of paretic upper extremity reaching, Wolf Motor Function Test (WMFT) and Stroke Impact Scale (SIS). Data were analyzed across time, with effect sizes (Cohen's d), and by categorizing participants with Fugl Meyer Upper Extremity Motor Assessment scores (mild >50/66, moderate 26-50/66 and severe <26/66). RESULTS: Statistically, significant improvements and medium-to large effect sizes from pretest to posttest were found with ipsilateral reaching kinematic outcomes of movement duration, mean velocity and elbow excursion (p < 0.05). Participants with mild impairment demonstrated the greatest change in elbow excursion. No significant differences and small effect sizes were found for the WMFT and SIS. CONCLUSION: The gaming intervention with high repetitions of reaching to targets and trunk restraint was feasible and led to improvements in upper extremity movement kinematics in this group of participants with chronic stroke. PMID- 22324474 TI - Odor potency of aroma compounds in Riesling and Vidal blanc table wines and icewines by gas chromatography-olfactometry-mass spectrometry. AB - This study aimed to elucidate the odor potency of aroma compounds in Riesling and Vidal blanc (syn. Vidal) table wines and icewines from the Niagara Peninsula using stir bar sorptive extraction-gas chromatography-olfactometry-mass spectrometry. Dilution analysis determined the most odor-potent compounds in Vidal and Riesling icewines (n = 2) and table wines (n = 2) from a commercial producer. The top 15 odor-potent compounds in each wine were identified and quantified, resulting in 23 and 24 compounds for Riesling and Vidal, respectively. The most odor-potent compounds were beta-damascenone, decanal, 1 hexanol, 1-octen-3-ol, 4-vinylguaiacol, ethyl hexanoate, and ethyl 3 methylbutyrate. In general, icewines had higher concentrations of most aroma compounds compared to table wines. Through computation of odor activity values, the compounds with the highest odor activity for the icewines were beta damascenone, 1-octen-3-ol, ethyl octanoate, cis-rose oxide, and ethyl hexanoate. In table wines the highest odor activity values were found for ethyl octanoate, beta-damascenone, ethyl hexanoate, cis-rose oxide, ethyl 3-methylbutyrate, and 4 vinylguaiacol. These findings provide a foundation to determine impact odorants in icewines and the effects of viticultural and enological practices on wine aroma volatile composition. PMID- 22324475 TI - Fabrication of anisotropic metal nanostructures using innovations in template assisted lithography. AB - Advances in the burgeoning field of plasmonics are increasingly dependent on the ability to fabricate metal nanostructures with precisely defined shapes and orientations, on a scale suitable for technological developments. Recent innovations in top-down lithography have created new windows of opportunity to produce anisotropic metal nanostructures en masse, with near-term applications in photonics, biosensing, and other nanotechnology-enabled pursuits. We focus specifically on C-shaped nanostructures (nanocrescents and split-ring resonators), which can be fabricated by using novel variants of shadow-mask lithography, substrate etching, or microcontact printing. PMID- 22324476 TI - Serum lipid levels and bone mineral density in Greek postmenopausal women. AB - Contradictory results have been reported regarding a relationship between serum lipid levels and bone mineral density. The purpose of this study was to further investigate a possible relationship between those parameters in Greek postmenopausal women. A total of 591 patients followed at a tertiary hospital were examined for seven different lipid factors in relation to dual-emission X ray absorptiometry measurements at the lumbar spine. Lipoprotein-a was the only lipid measurement that univariately showed an almost significant trend of association with bone mass category (analysis of variance [ANOVA] p value 0.062 for Ln(Lipoprotein-a)). In multiple regression, it was noted that a non significant negative trend of association of high density lipoprotein (HDL) cholesterol and Apolipoprotein AI with lumbar T-score (p value 0.058 and 0.075, respectively). In age subgroup analysis, Lipoprotein-a and Ln(Lipoprotein-a) presented a negative correlation with lumbar T-score for women with age >= 53 years (p value 0.043 and 0.070, respectively), while a negative correlation of HDL and Apolipoprotein AI levels with lumbar T-score remained in women with age < 53 years (p value 0.039 and 0.052, respectively). The findings do not support a strong relationship between lipid levels and bone mass measurements. PMID- 22324477 TI - Attraction of Stomoxys sp. to various fruits and flowers in Mali. AB - The attraction of three Stomoxys species to 26 fruits and 26 flowers of different plant species was investigated in two different sites in Mali during 2008. Stomoxys niger bilineatus Grunberg (Diptera: Muscidae) was attracted to a wider spectrum of species, significantly attracted by four fruits and eight flowers compared with control traps, whereas S. sitiens Rondani (Diptera: Muscidae) was attracted to six fruits and seven flowers of different plants, and S. calcitrans L. (Diptera: Muscidae) was only attracted to one fruit and three flowers. Cold anthrone assays showed a significantly higher prevalence of sugar feeding amongst all three species at the lagoon site than at the site near Mopti. The rhythm of activity study shows temporally separated blood- and sugar-feeding periods for S. niger bilineatus and S. sitiens, but not for S. calcitrans. A comparison between blood and sugar feeding throughout the day shows that sugar feeding activity is as frequent as blood feeding activity. Because not much is known about the preferred sugar sources for Stomoxys species in their natural habitats, the present study provides valuable information regarding the attraction capability of several plants with possible future implication for Stomoxys control strategies. PMID- 22324478 TI - The call for evidence-based drink and driving policies in Brazil. PMID- 22324479 TI - Differentiation of umbilical cord mesenchymal stem cells into steroidogenic cells in comparison to bone marrow mesenchymal stem cells. AB - OBJECTIVES: Human umbilical cord can be obtained easily and it represents a non controversial source of mesenchymal stem cells (MSCs) and umbilical cord Wharton's jelly-derived MSCs (UC-MSCs) have low immunogenicity. In this study, UC MSCs were induced to become steroidogenic cells and compared to bone marrow derived MSCs (BM-MSCs). MATERIAL AND METHODS: UC-MSCs and BM-MSCs were induced to differentiate into steroidogenic cells by infection with adenovirus containing SF 1. Expression of steroidogenic mRNA was analysed by real-time RT-PCR and steroid secretion was detected by ELISA testing. Viability of differentiated cells was examined using cell counting kit-8 assay. RESULTS: Both UC-MSCs and BM-MSCs expressed typical MSC markers and could differentiate into adipocytes, osteocytes and chondrocytes and both cell types had the potential to differentiate into steroidogenic cells after being infected with adenovirus containing SF-1 cDNA. However, UC-MSCs had significantly higher proliferative potential than BM-MSCs and differentiated UC-MSCs had significantly higher expression of all steroidogenic mRNAs tested over those of differentiated BM-MSCs; this included P450 side-chain cleavage enzyme, 3beta-HSD, 17beta-HSD type 3, LH-R, ACTH-R, P450c21 and CYP17. In addition, differentiated UC-MSCs secreted significantly more steroidogenic hormones than differentiated BM-MSCs, including testosterone and cortisol. Furthermore, differentiated UC-MSCs had significantly higher cell viability than differentiated BM-MSCs. CONCLUSIONS: UC-MSCs had significantly higher potential of steroidogenic differentiation than BM-MSCs; thus, UC-MSCs could be favourable cells of choice for cell-based therapy for steroidogenic insufficiency compared to BM-MSCs. PMID- 22324480 TI - The left ventricular intracavitary vortex during the isovolumic contraction period as detected by vector flow mapping. AB - AIMS: The purpose of this study was to characterize left ventricular (LV) intracavitary flow during the isovolumic contraction (IVC) period in humans using vector flow mapping. METHODS: Color flow Doppler imaging was performed from the apical long-axis view in 61 patients with heart failure and 58 healthy volunteers. Doppler flow data obtained during IVC were analyzed offline with vector flow mapping. RESULTS: A large vortex was formed from the LV inflow toward the outflow during IVC. In normal subjects, the area of the vortex was sustained, but the flow volume decreased significantly during IVC (P < 0.001). A significant apex-to-base flow velocity gradient was shown along the outflow axis on aortic valve opening. However, both the area and flow volume of the vortex decreased more severely during IVC in the patients (P < 0.001). The apex-to-base flow velocity gradient along the outflow axis disappeared and a reversed velocity gradient was observed at the basal-mid level on aortic valve opening. In multivariate models, a decreased LV ejection fraction was the only independent predictor of the percentage decrease in area of the vortex during the IVC (P < 0.001), and a larger QRS width (P = 0.028) and LV end-systolic long diameter (P = 0.002) were independent predictors of the percentage decrease in flow volume of the vortex. CONCLUSIONS: The vortex across the LV inflow-outflow region during IVC facilitates the ejection of blood during early systole, and an unsustained vortex may be associated with impaired cardiac function. PMID- 22324481 TI - Low-temperature, solution-processed MoO(x) for efficient and stable organic solar cells. AB - Sol-gel processed MoO(x) (sMoO(x)) hole-extraction layers for organic solar cells are reported. A Bis(2,4-pentanedionato)molybdenum(VI)dioxide/isopropanol solution is used and only a moderate thermal post deposition treatment at 150 degrees C in N(2) ambient is required to achieve sMoO(x) layers with a high work-function of 5.3 eV. We demonstrate that in P3HT:PC(60)BM organic solar cells (OSCs) our sMoO(x) layers lead to a high filling factor of about 65% and an efficiency of 3.3% comparable to that of reference devices with thermally evaporated MoO(3) layers (eMoO(3)). At the same time, a substantially improved stability of the OSCs compared to devices using a PEDOT:PSS hole extraction layer is evidenced. PMID- 22324482 TI - Retracted: Telescopic crown-retained removable partial dentures on teeth and implants: an 8- to 9-year prospective randomized clinical trial. PMID- 22324483 TI - Viability kinetics, induction, resuscitation and quantitative real-time polymerase chain reaction analyses of viable but nonculturable Vibrio cholerae O1 in freshwater microcosm. AB - AIM: To study the induction of a viable but nonculturable (VBNC) state in Vibrio cholerae O1 in freshwater, in response to cold temperatures (4 degrees C) and starvation. METHODS AND RESULTS: Vibrio cholerae O1 cells were inoculated in freshwater microcosm and incubated at 4 degrees C. The cells became coccoid, rugose and subsequently nonculturable by day 16 on tryptic soy agar (TSA) and by day 23 on TSA-SP, while 87 and 65% of the cells retained their membrane integrity, respectively. Viable cells were observed until day 30 using direct fluorescent antibody-direct viable count method. In vitro resuscitation was demonstrated by temperature upshift. Utilizing 16S rRNA as an endogenous control, the DNA pol II (27.43-fold), fliG (12.44-fold), ABC transporter (27.11-fold), relA (60.76-fold) and flaC (15.29-fold) were significantly up-regulated in VBNC cells, while the expression of fadL-3 was comparable. The expression of DNA pol II, fliG, ABC transporter, relA and flaC was 3.3, 1.1, 5.9, 5.8 and 1.2-fold, respectively, for resuscitated cells. VBNC cells were found to be virulent, as ctxA and tcpA were expressed. CONCLUSIONS: Vibrio cholerae undergoes both phenotypic alteration and genotypic modulation to protect itself from stress in freshwater. SIGNIFICANCE AND IMPACT OF THE STUDY: Induction and resuscitation of the VBNC state in freshwater is important for an understanding of the epidemiology of cholera in the freshwater environment. PMID- 22324484 TI - Soluble electron shuttles can mediate energy taxis toward insoluble electron acceptors. AB - Shewanella species grow in widely disparate environments and play key roles in elemental cycling, especially in environments with varied redox conditions. To obtain a system-level understanding of Shewanella's robustness and versatility, the complex interplay of cellular growth, metabolism, and transport under conditions of limiting carbon sources, energy sources, and electron acceptors must be elucidated. In this paper, population-level taxis of Shewanella oneidensis MR-1 cells in the presence of a rate-limiting, insoluble electron acceptor was investigated. A novel mechanism, mediated energy taxis, is proposed by which Shewanella use riboflavin as both an electron shuttle and an attractant to direct cell movement toward local sources of insoluble electron acceptors. The cells secrete reduced riboflavin, which diffuses to a nearby particle containing an insoluble electron acceptor and is oxidized. The oxidized riboflavin then diffuses away from the particle, establishing a spatial gradient that draws cells toward the particle. Experimental and modeling results are presented to support this mechanism. S. oneidensis MR-1 cells inoculated into a uniform dispersion of MnO(2) particles in dilute agar exhibited taxis outward, creating a clear zone within which riboflavin was detected by mass spectrometry. Cells inoculated into dilute agar containing oxidized riboflavin similarly exhibited taxis, rapidly forming an expanding zone of reduced riboflavin. A mathematical model based on the proposed mechanism was able to predict experimental trends, including how concentrations of riboflavin and insoluble electron acceptors (e.g., MnO(2)) affected tactic cell migration. PMID- 22324485 TI - Immunohistochemical analysis of pulpal regeneration by nestin expression in replanted teeth. AB - AIM: To investigate dental pulp healing after tooth replantation in rats using nestin as an odontoblastic marker for immunohistochemical analysis. METHODOLOGY: Twenty-five maxillary right first molars from 25 female Sprague-Dawley rats, aged 4 weeks post-natally, were extracted and immediately repositioned in the original socket within 5 s. Five rats each were later killed on days 3, 5 and weeks 1, 2 and 4. The maxillae were removed en bloc and the tissue samples containing the maxillary right first molars were decalcified, sectioned, mounted and stained with anti-nestin antibody to be observed under a light microscope. RESULTS: At 3 days after replantation, there was a localized inflammatory reaction, but pulp revascularization and healing had begun in the root area. At 5 days after replantation, odontoblast-like cells were observed. Reparative dentine deposition was observed beneath the pulp-dentine border from 1 week after replantation, and gradually increased until 2 weeks after replantation. The presence of odontoblast-like cells and the formation of reparative dentine continued from the first week throughout the experimental period. At week four, deposition of osteodentine and cementum-like tissues were observed. CONCLUSIONS: Pulpal mineralization after replantation initially occurred via the deposition of reparative dentine, followed by the deposition of osteodentine and cementum-like tissues in rat teeth. PMID- 22324486 TI - Lifestyle changes - a continuous, inner struggle for women with type 2 diabetes: a qualitative study. AB - OBJECTIVE: The objective of this study was to describe how women handle necessary lifestyle changes due to a chronic disease using diabetes as a model. DESIGN: Interview study. SETTING: Ten women living in western Sweden were interviewed. METHOD: In-depth interviews and analysis were performed using the phenomenological ideas of Giorgi. SUBJECTS: Ten women diagnosed with type 2 diabetes, mean age 65. All were either on disability pension or retired with varying complications ranging from none to stroke. RESULTS: The findings revealed five themes: the ambiguous feeling of others' involvement, becoming a victim of pressurizing demands, experiencing knowledge deficits, experiencing an urge, and finding reasons to justify not changing. The invariant meaning of a continuous inner struggle illuminates the experience of making lifestyle changes for women with type 2 diabetes. CONCLUSION: The findings of the present study show that it is vital for health care professionals to treat women diagnosed with type 2 diabetes with great respect and understanding regarding the struggle that they are going through. By being aware of the everyday burden for these women, acknowledging the fact that they want their lives to go on as before, may serve as a "key" to assist women in changing attitudes towards living in accordance with the disease and appreciating the lifestyle changes as a challenge as they become healthier and improve their quality of life. PMID- 22324487 TI - Assessment of risk factors for in-hospital mortality after intensive care unit discharge. AB - CONTEXT: Post-intensive care unit (ICU) mortality predictors are unknown. OBJECTIVE: To assess post-ICU in-hospital mortality predictors. MATERIALS AND METHODS: Analysis of 296 patients discharged alive from a medical-surgical ICU during an 18-month period. RESULTS: Post-ICU in-hospital mortality was 22.6%. Nonsurvivors had significantly higher Charlson comorbidity score and more often had a tracheostomy. C-reactive protein (CRP) "alert measurement", >= 6 mg/dL, independently discriminated survivors from nonsurvivors. DISCUSSION: A CRP "alert measurement" or the need for tracheostomy may be used to identify patients with high risk of dying after ICU discharge. CONCLUSIONS: Charlson comorbidity score, CRP and tracheostomy predicted post-ICU in-hospital mortality. PMID- 22324488 TI - Azithromycin as an adjunctive treatment of generalized severe chronic periodontitis: clinical, microbiologic, and biochemical parameters. AB - BACKGROUND: This study examines the efficacy of azithromycin in combination with non-surgical periodontal therapy on clinical and microbiologic parameters and gingival crevicular fluid (GCF) matrix metalloproteinases-8 (MMP-8) levels over 6 months in patients with severe generalized chronic periodontitis (CP). METHODS: Twenty-eight of 36 patients with severe generalized CP were included in this randomized, double-masked, placebo-controlled, parallel-arm study. They were randomly assigned to azithromycin or placebo groups (500 mg, once daily for 3 days). Probing depth (PD), clinical attachment level, dichotomous presence or absence of supragingival plaque accumulation, and bleeding on probing were recorded. GCF samples were obtained from one single-rooted tooth with PD >= 6 mm, whereas microbiologic samples were collected from two single-rooted teeth with PD >= 6 mm. Microbiologic parameters were analyzed by quantitative real-time polymerase chain reaction for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, Prevotella intermedia, and total bacteria. GCF MMP-8 levels were determined by immunofluorescence assay. RESULTS: Azithromycin and placebo groups demonstrated similar but significant improvements in all clinical parameters (P <0.05). A. actinomycetemcomitans, P. gingivalis, T. forsythia, P. intermedia, and total bacteria significantly decreased over the 6-month period in both groups, whereas F. nucleatum was significantly reduced in all visits in the azithromycin group, with the levels also being lower compared with those of the placebo group (P <0.05). The azithromycin and placebo groups exhibited significant reduction in GCF MMP-8 levels at the post-treatment visit and at 2 weeks (P <0.05). CONCLUSION: On the basis of the present findings, it can be concluded that adjunctive azithromycin provides no additional benefit over non-surgical periodontal treatment on parameters investigated in patients with severe generalized CP. PMID- 22324489 TI - Advances in surveillance of periodontitis: the Centers for Disease Control and Prevention periodontal disease surveillance project. AB - The Centers for Disease Control and Prevention (CDC) has as one of its strategic goals to support and improve surveillance of periodontal disease. In 2003, the CDC initiated the CDC Periodontal Disease Surveillance Project in collaboration with the American Academy of Periodontology to address population-based surveillance of periodontal disease at the local, state, and national levels. This initiative has made significant advancements toward the goal of improved surveillance, including developing valid self-reported measures that can be obtained from interview-based surveys to predict prevalence of periodontitis in populations. This will allow surveillance of periodontitis at the state and local levels and in countries where clinical resources for surveillance are scarce. This work has produced standard case definitions for surveillance of periodontitis that are now widely recognized and applied in population studies and research. At the national level, this initiative has evaluated the validity of previous clinical examination protocols and tested new protocols on the National Health and Nutrition Examination Survey (NHANES), recommending and supporting funding for the gold-standard full-mouth periodontal examination in NHANES 2009 to 2012. These examinations will generate accurate estimates of the prevalence of periodontitis in the US adult population and provide a superior dataset for surveillance and research. Also, this data will be used to generate the necessary coefficients for our self-report questions for use in subsets of the total US population. The impact of these findings on population-based surveillance of periodontitis and future directions of the project are discussed along with plans for dissemination and translation efforts for broader public health use. PMID- 22324490 TI - Use of an expanded immunohistochemical panel to distinguish cutaneous Hodgkin lymphoma from histopathologic imitators. AB - In lymph nodes, classical Hodgkin lymphoma can typically be distinguished from non-Hodgkin lymphoma (NHL) by the presence of Hodgkin and Reed-Sternberg cells that co-express CD30 and CD15. However, anaplastic large cell lymphoma (ALCL) and diffuse large B-cell lymphoma (DLBCL) can show identical features, and some cases of classical Hodgkin lymphoma lack CD15 expression, rendering them difficult to differentiate from CD30-positive NHL. The differential diagnosis of cutaneous Hodgkin lymphoma similarly includes ALCL and DLBCL, and, additionally, tumors of mycosis fungoides. Recent studies have shown that classical Hodgkin lymphoma is of B-cell origin in virtually all cases, and shows at least focal weak expression of the B-cell marker PAX5 and often focal weak expression and no expression of the B-cell markers Oct-2 and BOB.1, respectively. All three of these markers are almost invariably absent in T-cell lymphomas and are strongly expressed in B-cell lymphomas. We report a 40-year-old man with classical Hodgkin lymphoma who developed cutaneous nodules. A biopsy from one revealed Hodgkin/Reed-Sternberg cells with a similar immunophenotype to the diagnostic lymph node biopsy, namely CD30+/CD15+, diffusely but weakly PAX5+, focally weakly Oct-2+ and lacking BOB.1 expression, thereby confirming a diagnosis of cutaneous Hodgkin lymphoma. To our knowledge, this is the first report of the expression pattern of the combination of PAX5, Oct-2 and BOB.1 in the context of cutaneous involvement by Hodgkin lymphoma. PMID- 22324493 TI - Fumes from the spleen. (Mis)measuring. PMID- 22324494 TI - The effects of exposure to particulate matter and neighbourhood deprivation on gestational hypertension. AB - Gestational hypertension, pre-eclampsia and eclampsia are conditions that affect the health of both mothers and infants during and after pregnancy. Recent research indicates the importance of considering environmental, social and individual contributors to poor pregnancy outcomes. Our research examined particulate matter (PM) concentrations as one measure of environmental exposure and neighbourhood quality as one measure of the social environment. We used these measures, as well as maternal characteristics, to predict the risk of gestational hypertension (including pre-eclampsia and eclampsia). North Carolina Detailed Birth Record data for 2000-2003 were obtained and geocoded for all singleton births. Levels of PM(10) and PM(2.5) were determined using air quality data from the US Environmental Protection Agency. Information on a woman's residential neighbourhood was determined from 2000 Census data. Modified Poisson regression models clustered by tract were used to examine the associations between PM levels, neighbourhood deprivation and maternal characteristics with gestational hypertension. Analysis was restricted to women residing within 20 km of a PM monitor. Both PM(10) and PM(2.5) were associated with gestational hypertension; the risk ratios for an interquartile range (IQR) increase in exposure were 1.07 [95% confidence interval (CI) 1.04, 1.11] for PM(10) (IQR: 3.92 ug/m(3)) and 1.11 [95% CI 1.08, 1.15] for PM(2.5) (IQR: 2.24 ug/m(3)). Living in a neighbourhood with increased levels of deprivation was also associated with gestational hypertension. Any smoking during pregnancy, younger age and higher level of education were inversely associated with risk of gestational hypertension. Compared with non-Hispanic White women, non-Hispanic Black women were at higher risk of gestational hypertension, whereas Hispanic women were at lower risk. Increased levels of PM and neighbourhood deprivation, as well as certain individual characteristics, were associated with higher risk of gestational hypertension. PMID- 22324495 TI - Do hypertensive diseases of pregnancy disrupt neurocognitive development in offspring? AB - The current study sought to determine whether hypertensive diseases of pregnancy (gestational hypertension and pre-eclampsia) are associated with neurocognitive outcomes in middle childhood. Participants were members of the Western Australian Pregnancy Cohort (Raine) Study. Data were available for 1389 children (675 females; mean age = 10.59 years; SD = 0.19). Twenty-five per cent of these participants were offspring of pregnancies complicated by either gestational hypertension (n = 279), or pre-eclampsia (n = 34). Verbal ability at age 10 years was assessed with the Peabody Picture Vocabulary Test - Revised (PPVT-R), and non verbal ability with Ravens Colored Progressive Matrices (RCPM). Separate multivariable regression analyses, incorporating sociodemographic, antenatal, obstetric and postnatal covariates, investigated the effect of a two- (normotensive pregnancy vs. hypertensive pregnancy) and three-level (normotensive pregnancy vs. gestational hypertension vs. pre-eclampsia) predictor variable on PPVT-R and RCPM scores. Offspring of pregnancies complicated by maternal hypertension (gestational hypertension or pre-eclampsia) had a mean PPVT-R score that was 1.83 ([95% confidence interval (CI) -3.48, -0.17], P = 0.03) points lower than children from normotensive pregnancies. Multivariable regression analysis also identified a significant inverse association between the three level predictor variable and offspring PPVT-R scores (P = 0.02). Gestational hypertension (without pre-eclampsia) reduced offspring PPVT-R scores by 1.71 points [95% CI -3.39, -0.03] and pre-eclampsia led to a reduction of 3.53 points [95% CI -8.41, 1.35], although this latter association did not achieve statistical significance. There was no effect of the two- (P = 0.99) or three level (P = 0.92) predictor variable on RCPM scores. Maternal hypertensive diseases of pregnancy are a risk factor for a small reduction in offspring verbal ability. PMID- 22324496 TI - The bias in current measures of gestational weight gain. AB - Conventional measures of gestational weight gain (GWG), such as average rate of weight gain, are likely to be correlated with gestational duration. Such a correlation could introduce bias to epidemiological studies of GWG and adverse perinatal outcomes because many perinatal outcomes are also correlated with gestational duration. This study aimed to quantify the extent to which currently used GWG measures may bias the apparent relationship between maternal weight gain and risk of preterm birth. For each woman in a provincial perinatal database registry (British Columbia, Canada, 2000-2009), a total GWG was simulated such that it was uncorrelated with risk of preterm birth. The simulation was based on serial antenatal GWG measurements from a sample of term pregnancies. Simulated GWGs were classified using three approaches: total weight gain (kg), average rate of weight gain (kg/week) or adequacy of GWG in relation to Institute of Medicine recommendations. Their association with preterm birth <=32 weeks was explored using logistic regression. All measures of GWG induced an apparent association between GWG and preterm birth <=32 weeks even when, by design, none existed. Odds ratios in the lowest fifths of each GWG measure compared with the middle fifths ranged from 4.4 [95% confidence interval (CI) 3.6, 5.4] (total weight gain) to 1.6 [95% CI 1.3, 2.0] (Institute of Medicine adequacy ratio). Conventional measures of GWG introduce serious bias to the study of maternal weight gain and preterm birth. A new measure of GWG that is uncorrelated with gestational duration is needed. PMID- 22324497 TI - Do medical certificates of stillbirth provide accurate and useful information regarding the cause of death? AB - Stillbirth affects one in 200 pregnancies in the UK. Understanding the causes of stillbirth is essential to reducing perinatal mortality. Stillbirth certificates represent a potential source of data on perinatal mortality. We aimed to assess whether the information on stillbirth certificates used in the UK is accurate. A retrospective cross-sectional audit of stillbirth certificates issued in a geographical region of the UK in 2009 was undertaken. Data were recorded from the stillbirth certificate and health records. The cause of death was classified using the ReCoDe system. Two hundred and thirteen stillbirth certificates were issued for stillbirths (feticides for fetal anomaly were excluded). Agreement for the primary factor associated with the stillbirth was fair (Kappa = 0.286). This contrasts with the gestation of stillbirth, which was almost complete agreement (Kappa = 0.883). The majority of stillbirths (58.7%) were classified on the certificate as 'unknown cause'. A proportion of 9.4% of stillbirths were classified as congenital anomaly and 8.0% as placental abruption. Only 0.5% of stillbirth certificates cited fetal growth restriction as a relevant condition contributing to death. A total of 49.6% of 'unexplained' stillbirths were associated with fetal growth restriction on review. Errors were present in 77.9% of certificates, including missing co-morbidities (55.9%) and the wrong cause of death (40.4%). The cause(s) of death is (are) not recorded accurately on the UK medical certificate of stillbirth, and the majority of certificates contain one or more errors. Training is required to improve understanding of the causes of stillbirth and completion of medical certificates. Data recorded directly from medical certificate of stillbirths are not sufficiently reliable for descriptive studies of causation and epidemiology. PMID- 22324498 TI - Temporal trends in sudden infant death syndrome in Canada from 1991 to 2005: contribution of changes in cause of death assignment practices and in maternal and infant characteristics. AB - The rate of sudden infant death syndrome (SIDS) declined significantly in Canada and the US between the late 1980s and the early 2000s. In the US, this decline was shown to be due in part to a shift in diagnosis, as deaths from accidental suffocation and strangulation in bed and from other ill-defined and unspecified cause increased concurrently. This study was undertaken to determine whether there was such a shift in diagnosis from SIDS to other causes of death in Canada, and to quantify the true temporal decrease in SIDS. Cause-specific infant death rates were compared across three periods: 1991-95, 1996-2000 and 2001-05 using the Canadian linked livebirth-infant death file. The temporal decline in SIDS was estimated after adjustment for maternal and infant characteristics such as maternal age and small-for-gestational age using logistic regression. Deaths from SIDS decreased from 78.4 [95% confidence interval (CI) 73.4, 83.4] per 100 000 livebirths in 1991-95, to 48.5 [95% CI 44.3, 52.7] in 1996-2000 and to 34.6 [95% CI 31.0, 38.3] in 2001-05. Mortality rates from other ill-defined and unspecified causes and accidental suffocation and strangulation in bed remained stable. The temporal decline in SIDS between 1991-95 and 2001-05 did not change substantially after adjustment for maternal and infant factors. It is unlikely that the temporal decline of SIDS in Canada was due to changes in cause-of-death assignment practices or in maternal and infant characteristics. PMID- 22324499 TI - Projections of diagnosed HIV infection in children and adolescents in New York State. AB - Decreasing mother-to-child transmission is changing the population of children and adolescents with HIV. This project used recent epidemiological data to develop short-term projections of children and adolescents living with diagnosed HIV infection in New York State. A population simulation model was created to project prevalence of diagnosed HIV cases aged 0-19 years by age, sex, race/ethnicity and risk for years 2007-2014. Using 2006 data as the baseline population and 2001-2006 diagnosis and death data, annual diagnoses and deaths were calculated for each age/sex/race/risk category and known cases were 'aged' into the next year. The model produced annual estimates until 2014. The model predicts a decline in the number of persons aged 0-19 years living with diagnosed HIV in New York from 2810 in 2006 to 1431 in 2014, a net decrease of 49%. Living cases with paediatric risk continue to decrease. Cases aged 13-19 with non paediatric risk increase slowly, leading to a shift in the risk composition of the population. The dominant effect seen in the model is the ageing out of perinatally infected children born before measures to prevent mother-to-child transmission were broadly implemented in the mid- to late 1990s. Changing trends in the young HIV-infected population should be considered in developing public health programmes for HIV prevention and care in New York State for the coming years. PMID- 22324500 TI - Atopic diseases in twins born after assisted reproduction. AB - We examined the risk of atopic diseases in twins born after assisted reproduction. Data on atopic diseases and assisted reproduction in 9694 twin pairs, 3-20 years of age, from the Danish Twin Registry were collected via multidisciplinary questionnaires. The risk of atopic diseases in twins born after assisted reproduction was compared with the risk in twins born after spontaneous conception using logistic regression and variance components analysis. Children born after assisted reproduction did not have a different risk of atopic outcomes (adjusted odds ratios [95% confidence intervals] for asthma: 0.95 [0.85, 1.07], P = 0.403; hay fever: 1.01 [0.86, 1.18], P = 0.918; and atopic dermatitis: 1.02 [0.81, 1.11], P = 0.773 respectively) compared with children born after spontaneous conception. Assisted reproduction did not modify the heritability of atopic diseases. This study does not support an association between assisted reproduction and development of atopic diseases. This result must be confirmed in subsequent studies, preferably of singleton populations. PMID- 22324501 TI - The risk factors and quality of life in children with allergic rhinitis in relation to seasonal attack patterns. AB - A questionnaire survey was conducted to examine whether risk factors and allergic rhinitis (AR)-related quality of life (QOL) were different among children with different seasonal patterns of AR. Participants were students enrolled in elementary and middle schools in Taipei County, Taiwan. Using moving average and principal component analysis, children with current AR were grouped by attack seasons. The effects of personal and environmental factors on AR seasonality were assessed by logistic regression models. AR severity and AR-related QOL were compared within AR seasonal subtypes. Among 4221 children who completed the questionnaire, 1144 and 1605 children were current AR cases and healthy controls, respectively. Four AR subtypes were categorised as follows: perennial, spring, summer/fall, and winter. Age, gender, parental education, maternal passive smoking during pregnancy, breast feeding, and mouldy walls were found to contribute differentially to different AR subtypes. Children suffering from perennial and winter AR were found to have more severe symptoms and significantly lower QOL score compared with other subtypes. Specific personal and environmental risk factors could contribute to different AR seasonal subtypes. Active allergen avoidance and symptomatic treatment should be the focus of management aiming to improve the QOL among children with perennial and winter subtype. PMID- 22324502 TI - The prevalence and risk factors of infantile haemangiomas: a case-control study in the Dutch population. AB - Haemangiomas are considered to be the most common tumours of infancy. However, despite their frequent occurrence the aetiological determinants of their development remain unknown. Identifying these factors may provide insight on their pathogenesis. We performed cross-sectional screening for haemangiomas in newborns (0-16 months of age) in the general Dutch population. Haemangioma specific and pregnancy-related data were collected in children with a haemangioma. These data were compared in a case-control design using multivariable logistic regression analysis. Among 2204 newborns, 219 (9.9%) had a haemangioma. The male-to-female ratio was 1:2. The majority of haemangiomas were located on the trunk (37%). The general practitioners or medical specialists were consulted in only a minority of cases (<7%). Amniocentesis [odds ratio (OR) 3.6, 95% confidence interval (CI) 1.11, 11.42], breech presentation [OR 2.3, 95% CI 1.14, 4.44], being first-born [OR 1.55, 95% CI 1.03, 2.33] and a birthweight <=2500 g [OR 4.95, 95% CI 1.63, 15.05] were independent factors associated with the development of a haemangioma. Duration of pregnancy did not differ between study groups. Our study showed that the prevalence of a haemangioma is 9.9% in the general (Dutch) population. Four factors appear relevant in the development of haemangiomas. These factors may provide clues to its pathogenesis. PMID- 22324503 TI - Early-life soy exposure and age at menarche. AB - This study examines the timing of menarche in relation to infant-feeding methods, specifically addressing the potential effects of soy isoflavone exposure through soy-based infant feeding. Subjects were participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Mothers were enrolled during pregnancy and their children have been followed prospectively. Early-life feeding regimes, categorised as primarily breast, early formula, early soy and late soy, were defined using infant-feeding questionnaires administered during infancy. For this analysis, age at menarche was assessed using questionnaires administered approximately annually between ages 8 and 14.5. Eligible subjects were limited to term, singleton, White females. We used Kaplan-Meier survival curves and Cox proportional hazards models to assess age at menarche and risk of menarche over the study period. The present analysis included 2920 girls. Approximately 2% of mothers reported that soy products were introduced into the infant diet at or before 4 months of age (early soy). The median age at menarche [interquartile range (IQR)] in the study sample was 153 months [144-163], approximately 12.8 years. The median age at menarche among early soy-fed girls was 149 months (12.4 years) [IQR, 140-159]. Compared with girls fed non-soy-based infant formula or milk (early formula), early soy-fed girls were at 25% higher risk of menarche throughout the course of follow-up (hazard ratio 1.25 [95% confidence interval 0.92, 1.71]). Our results also suggest that girls fed soy products in early infancy may have an increased risk of menarche specifically in early adolescence. These findings may be the observable manifestation of mild endocrine-disrupting effects of soy isoflavone exposure. However, our study is limited by few soy exposed subjects and is not designed to assess biological mechanisms. Because soy formula use is common in some populations, this subtle association with menarche warrants more in-depth evaluation in future studies. PMID- 22324505 TI - High-pressure homogenization lowers water vapor permeability of soybean protein isolate-beeswax films. AB - Soybean-protein isolate (SPI) has excellent film-forming capacity. However, the water vapor permeability of SPI film is high, which will cause the moisture lose of packaged products. The effect of high-pressure homogenization (HPH) on the water vapor permeability of SPI-beeswax films was evaluated. The HPH was effective at lowering the water vapor permeability of SPI-beeswax films to about 50% of the control. The HPH reduced the particle size of films and made their matrix more compact. The HPH improved the hydrophobicity of SPI-beeswax films. For the first time, we proved that the HPH improved the bound-beeswax content in SPI-beeswax films. The bound beeswax was effective at lowering the water vapor permeability of films rather than the free beeswax in the film matrix. In summary, the HPH lowered water vapor permeability of SPI-beeswax films by reducing their particle size and raising their hydrophobicity and bound-beeswax content. PMID- 22324506 TI - Derivation of male germ cells from induced pluripotent stem cells in vitro and in reconstituted seminiferous tubules. AB - OBJECTIVES: Previous studies have demonstrated that mouse- and human-induced pluripotent stem (iPS) cells can differentiate into primordial germ cells in vitro. However, up to now it is not known whether iPS cells would be able to differentiate into male germ cells in vivo. The aim of this study was to explore differentiation potential of iPS cells to male germ cells in vitro and in vivo. MATERIALS AND METHODS: In this study, approaches using in vitro retinoic acid induction and in vivo ectopic transplantation were combined to induce iPS cells to become male germ cells. RESULTS: RT-PCR showed that expression of pre-meiotic and meiotic germ cell-specific genes was enhanced in iPS cell-derived embryoid bodies (EBs) compared to mRNA transcripts of iPS cells. Immunofluorescence analysis revealed that iPS cell-derived EBs positively expressed germ-cell markers VASA, c-Kit and SCP3. Furthermore, iPS cell-derived cells dissociated from EBs were injected with testicular cells into dorsal skin of mice. Histological examination showed that iPS cell-derived cells could reconstitute seminiferous tubules, and meanwhile, iPS cell-derived germ cells could settle at basement membranes of reconstituted tubules. CONCLUSION: Our results suggest that iPS cells are able to differentiate into male germ cells in vitro and that reconstituted seminiferous tubules may provide a functional niche for exogenous iPS cell-derived male germ cells. Derivation of male germ cells from iPS cells has potential application for treating male infertility and provides an ideal platform for elucidating molecular mechanisms of male germ-cell development. PMID- 22324507 TI - Physical defect formation in few layer graphene-like carbon on metals: influence of temperature, acidity, and chemical functionalization. AB - A systematical examination of the chemical stability of cobalt metal nanomagnets with a graphene-like carbon coating is used to study the otherwise rather elusive formation of nanometer-sized physical defects in few layer graphene as a result of acid treatments. We therefore first exposed the core-shell nanomaterial to well-controlled solutions of altering acidity and temperature. The release of cobalt into these solutions over time offered a simple tool to monitor the progress of particle degradation. The results suggested that the oxidative damage of the graphene-like coatings was the rate-limiting step during particle degradation since only fully intact or entirely emptied carbon shells were found after the experiments. If ionic noble metal species were additionally present in the acidic solutions, the noble metal was found to reduce on the surface of specific, defective particles. The altered electrochemical gradients across the carbon shells were however not found to lead to a faster release of cobalt from the particles. The suggested mechanistic insight was further confirmed by the covalent chemical functionalization of the particle surface with chemically inert aryl species, which leads to an additional thickening of the shells. This leads to reduced cobalt release rates as well as slower noble metal reduction rates depending on the augmentation of the shell thickness. PMID- 22324508 TI - Introduction: use of radioactive compounds in drug discovery and development. PMID- 22324509 TI - Dissemination of evidence-based practices: how far we've come, and how much further we've got to go. PMID- 22324510 TI - Kinesiophobia, catastrophizing and anticipated symptoms before stair climbing in chronic fatigue syndrome: an experimental study. AB - PURPOSE: Kinesiophobia and catastrophizing are frequent among people with chronic fatigue syndrome (CFS). This study was aimed at examining (1) whether kinesiophobia, anticipated symptoms and fatigue catastrophizing are related to stair climbing performance in people with CFS; and (2) whether kinesiophobia and fatigue catastrophizing are related to daily physical activity in CFS. METHOD: Patients with CFS filled in a set of questionnaires, performed a physical demanding task (two floors stair of climbing and descending) with pre-test and post-test heart rate monitoring and immediate post-stair climbing symptom assessment. Real-time activity monitoring was used between the baseline and second assessment day (7 days later). RESULTS: Kinesiophobia and fatigue catastrophizing were strongly related (rho = 0.62 and 0.67, respectively) to poorer stair climbing performance (i.e. more time required to complete the threatening activity). Kinesiophobia and fatigue catastrophizing were unrelated to the amount of physical activity on the first day following stair climbing or during the seven subsequent days. CONCLUSION: These findings underscore the importance of kinesiophobia and fatigue catastrophizing for performing physical demanding tasks in everyday life of people with CFS, but refute a cardinal role for kinesiophobia and fatigue catastrophizing in determining daily physical activity level in these patients. PMID- 22324511 TI - Diffusion-assisted high-resolution direct femtosecond laser writing. AB - We present a new method for increasing the resolution of direct femtosecond laser writing by multiphoton polymerization, based on quencher diffusion. This method relies on the combination of a mobile quenching molecule with a slow laser scanning speed, allowing the diffusion of the quencher in the scanned area and the depletion of the multiphoton-generated radicals. The material we use is an organic-inorganic hybrid, while the quencher is a photopolymerizable amine-based monomer which is bound on the polymer backbone upon fabrication of the structures. We use this method to fabricate woodpile structures with a 400 nm intralayer period. This is comparable to the results produced by direct laser writing based on stimulated-emission-depletion microscopy, the method considered today as state-of-the-art in 3D structure fabrication. We optically characterize these woodpiles to show that they exhibit well-ordered diffraction patterns and stopgaps down to near-infrared wavelengths. Finally, we model the quencher diffusion, and we show that radical inhibition is responsible for the increased resolution. PMID- 22324512 TI - Functional efficacy of adenosine A2A receptor agonists is positively correlated to their receptor residence time. AB - BACKGROUND AND PURPOSE The adenosine A(2A) receptor belongs to the superfamily of GPCRs and is a promising therapeutic target. Traditionally, the discovery of novel agents for the A(2A) receptor has been guided by their affinity for the receptor. This parameter is determined under equilibrium conditions, largely ignoring the kinetic aspects of the ligand-receptor interaction. The aim of this study was to assess the binding kinetics of A(2A) receptor agonists and explore a possible relationship with their functional efficacy. EXPERIMENTAL APPROACH We set up, validated and optimized a kinetic radioligand binding assay (a so-called competition association assay) at the A(2A) receptor from which the binding kinetics of unlabelled ligands were determined. Subsequently, functional efficacies of A(2A) receptor agonists were determined in two different assays: a novel label-free impedance-based assay and a more traditional cAMP determination. KEY RESULTS A simplified competition association assay yielded an accurate determination of the association and dissociation rates of unlabelled A(2A) receptor ligands at their receptor. A correlation was observed between the receptor residence time of A(2A) receptor agonists and their intrinsic efficacies in both functional assays. The affinity of A(2A) receptor agonists was not correlated to their functional efficacy. CONCLUSIONS AND IMPLICATIONS This study indicates that the molecular basis of different agonist efficacies at the A(2A) receptor lies within their different residence times at this receptor. PMID- 22324513 TI - Development of nanopatterned fluorine-doped tin oxide electrodes for dye sensitized solar cells with improved light trapping. AB - Transparent conductors (TCs) are an important component of optoelectronic devices and nanoscale engineering of TCs is important for optimization of the device performance through improved light trapping. In this work, patterned periodic arrays of nanopillars and nanolines of pitch size of ~700 nm were created on fluorine-doped tin oxide (FTO) using nanoimprint lithography and reactive ion etching using environmentally friendly gases. The patterned FTO exhibits enhanced light trapping as compared to the unpatterned FTO, which agrees well with simulations based on Finite-Difference Time-Domain method for up to a distance of 4 MUm. Dye sensitized solar cells (DSSCs) fabricated on the patterned FTO exhibited improved performance (fill factor and power conversion efficiency), which can be attributed to enhanced light absorption in the range 400-650 nm. Further, electrochemical impedance measurements revealed lower recombination resistance for the patterned FTO/TiO(2) electrode compared to the unpatterned FTO electrode/TiO(2) electrode as a result of better light capturing properties of patterned FTO. The direct fabrication of nanopatterns on TCs developed in the present study is expected to be a viable scheme for achieving improved performance in many other optoelectronic devices. PMID- 22324514 TI - Mercury vapor pressure of flue gas desulfurization scrubber suspensions: effects of pH level, gypsum, and iron. AB - Calcium-based scrubbers designed to absorb HCl and SO(2) from flue gases can also remove oxidized mercury. Dissolved mercury halides may have an appreciable partial vapor pressure. Chemical reduction of the dissolved mercury may increase the Hg emission, thereby limiting the coremoval of mercury in the wet scrubbing process. In this paper we evaluate the effects of the pH level, different gypsum qualities, and iron in flue gas desulfurization (FGD) scrubber suspensions. The impact of these parameters on mercury vapor pressure was studied under controlled laboratory conditions in model scrubber suspensions. A major influence is exerted by pH values above 7, considerably amplifying the mercury concentration in the vapor phase above the FGD scrubber suspension. Gypsum also increases the mercury re-emission. Fe(III) decreases and Fe(II) increases the vapor pressure significantly. The consequences of the findings for a reliable coremoval of mercury in FGD scrubbers are discussed. It is shown that there is an increased risk of poor mercury capture in lime-based FGD scrubbers in comparison to limestone FGD scrubbers. PMID- 22324515 TI - Bortezomib reverses the proliferative and antiapoptotic effect of neuropeptides on prostate cancer cells. AB - OBJECTIVES: Neuropeptides are important signal initiators in advanced prostate cancer, partially acting through activation of nuclear factor kappa B. Central to nuclear factor kappa B regulation is the ubiquitin-proteasome system, pharmacological inhibition of which has been proposed as an anticancer strategy. We investigated the putative role of the proteasome inhibitor bortezomib in neuropeptides signaling effects on prostate cancer cells. METHODS: Human prostate cancer cell lines, LNCaP and PC-3, were used to examine cell proliferation, levels of proapoptotic (caspase-3, Bad) and cell cycle regulatory proteins (p53, p27, p21), as well as total and phosphorylated Akt and p44/42 mitogen-activated protein kinase proteins. Furthermore, 20S proteasome activity, subcellular localization of nuclear factor kappa B and transcription of nuclear factor kappa B target genes, interleukin-8 and vascular endothelial growth factor, were assessed. RESULTS: Neuropeptides (endothelin-1, bombesin) increased cell proliferation, whereas bortezomib decreased proliferation and induced apoptosis, an effect maintained after cotreatment with neuropeptides. Bad, p53, p21 and p27 were downregulated by neuropeptides in PC-3, and these effects were reversed with the addition of bortezomib. Neuropeptides increased proteasomal activity and nuclear factor kappa B levels in PC-3, and these effects were prevented by bortezomib. Interleukin-8 and vascular endothelial growth factor transcripts were induced after neuropeptides treatment, but downregulated by bortezomib. These results coincided with the ability of bortezomib to reduce mitogen-activated protein kinase signaling in both cell lines. CONCLUSIONS: These findings are consistent with bortezomib-mediated abrogation of neuropeptides-induced proliferative and antiapoptotic signaling. Thus, the effect of the drug on the neuropeptides axis needs to be further investigated, as neuropeptide action in prostate cancer might entail involvement of the proteasome. PMID- 22324517 TI - Pseudomonas putida NBRIC19 dihydrolipoamide succinyltransferase (SucB) gene controls degradation of toxic allelochemicals produced by Parthenium hysterophorus. AB - AIMS: The aim of this study was to identify the gene responsible for degradation of toxic allelochemicals of Parthenium by generating Tn5-induced mutant of Pseudomonas putida NBRIC19. Furthermore, the study characterizes the mutant at physiological, biochemical and molecular level that helped in understanding the mechanisms of reducing the allelopathic inhibition of Parthenium by Ps. putida NBRIC19. METHODS AND RESULTS: Tn5 mutant S-74.3 showing inability to degrade toxic allelochemicals was selected after screening 22 000 transconjugants. Tn5 flanking SucB gene (dihydrolipoamide succinyltransferase) of Ps. putida NBRIC19 was found to be responsible for the degradation of toxic allelochemicals that also affected biofilm formation, chemotaxis and alginate production under toxic environment of allelochemicals. Phenotypic microarray data revealed that the respiratory activity of Ps. putida NBRIC19 and S-74.3 differed on 47 substrates including amino acids, carboxylic acids, peptides and some chemical inhibitors. CONCLUSIONS: Study revealed that SucB gene regulates processes either directly or indirectly in Ps. putida NBRIC19, which on inactivation made the mutant less compatible for tolerating stress. SIGNIFICANCE AND IMPACT OF THE STUDY: This work provides the first evidence for a functional role of Ps. putida SucB gene in degradation of toxic allelochemicals of Parthenium that lead to reversal of plant growth inhibition by these toxic allelochemicals. The investigation also revealed interesting features about the involvement of microbes in plant-plant allelopathic interactions. PMID- 22324516 TI - A double-blind, placebo-controlled trial assessing the efficacy of levetiracetam extended-release in very heavy drinking alcohol-dependent patients. AB - BACKGROUND: Despite advances in the development of medications to treat alcohol dependence, few medications have been approved by the U.S. Food and Drug Administration. The use of certain anticonvulsant medications has demonstrated potential efficacy in treating alcohol dependence. Previous research suggests that the anticonvulsant levetiracetam may be beneficial in an alcohol-dependent population of very heavy drinkers. METHODS: In this double-blind, randomized, placebo-controlled clinical trial, 130 alcohol-dependent patients who reported very heavy drinking were recruited across 5 clinical sites. Patients received either levetiracetam extended-release (XR) or placebo and a Brief Behavioral Compliance Enhancement Treatment intervention. Levetiracetam XR was titrated during the first 4 weeks to 2,000 mg/d. This target dose was maintained during weeks 5 through 14 and was tapered during weeks 15 and 16. RESULTS: No significant differences were detected between the levetiracetam XR and placebo groups in either the primary outcomes (percent heavy drinking days and percent subjects with no heavy drinking days) or in other secondary drinking outcomes. Treatment groups did not differ on a number of nondrinking outcomes, including depression, anxiety, mood, and quality of life. The only difference observed was in alcohol-related consequences. The levetiracetam XR treatment group showed significantly fewer consequences than did the placebo group during the maintenance period (p = 0.02). Levetiracetam XR was well tolerated, with fatigue being the only significantly elevated adverse event, compared with placebo (53% vs. 24%, respectively; p = 0.001). CONCLUSIONS: This multisite clinical trial showed no efficacy for levetiracetam XR compared with placebo in reducing alcohol consumption in heavy drinking alcohol-dependent patients. PMID- 22324518 TI - Predicting improvement after surgery for palmar hyperhidrosis. AB - OBJECTIVES: Endoscopic transthoracic sympathectomy (ETS) is a surgical procedure used to improve Quality of Life (QoL) in patients with treatment resistant palmar hyperhidrosis (PHH). The aim of this study was to test the hypothesis that low preoperative scores on The Everyday Life Questionnaire (EDLQ) would predict QoL improvement after surgery. MATERIALS AND METHODS: Pre- and post-operative QoL scores from a series of 30 consecutive patients who underwent ETS at our institution were analyzed. RESULTS: Preoperative QoL scores was a significant predictor of post-operative improvement across all dimensions covered by the questionnaire. CONCLUSION: Preoperative low QoL can be used as a guide in selecting patients with most improved QoL after ETS. PMID- 22324519 TI - Magnetocurrent of charge-polarizable C60-diphenylaminofluorene monoadduct-derived magnetic nanocomposites. AB - We demonstrated the strategy of a nanocomposite design by the incorporation of both a delocalized pi-electrons system in a closely bound acceptor-donor analogue chromophore, based on charge-polarizable C(60)(>DPAF-C(9)) nanostructure 1, and spin-polarized d-electrons in the form of gamma-FeO(x) nanoparticles. Facile intramolecular electron transfer from the DPAF-C(9) donor moiety to the C(60) acceptor cage of 1 upon activation to the excited state with a long lifetime of the charge-separated state forms a possible mechanism to integrate semiconducting and magnetic properties in a single system. We observed an appreciable magnetocurrent (MC) of C(60)(>DPAF-C(9))-encapsulated magnetic gamma-FeO(x) nanoparticles in PMMA matrix upon applying a magnetic field from 0 to 300 mT at either 77 K (12% MC) or 300 K (4.5% MC). Interestingly, the detailed analysis of magnetocurrent curve profiles taken at 77 K allowed us to conclude that the measured magnetocurrent may be attributed to the contributions from magnetic field-dependent excited-state populations in semiconducting structure (density based MC), magnetism from magnetic structure (mobility-based MC), and product of density and mobility-based MC components (pi-d electronic coupling). At the higher temperature region up to 300 K, the semiconducting mechanism dominated the determining factor of measured magnetocurrent. This experimental observation indicated the feasibility of combining delocalized pi electrons and spin polarized d electrons through charge transfer to induce internally coupled dual mobility- and density-based MC through the modulation of spin polarization and excited states in semiconducting/magnetic hybrid materials. PMID- 22324521 TI - Medical education and professionalism across different cultures. PMID- 22324522 TI - Testing non-cognitive attributes in selection centres: how to avoid being reliably wrong. PMID- 22324523 TI - Empathy, distress and a new understanding of doctor professionalism. PMID- 22324524 TI - A cross-cultural study of students' approaches to professional dilemmas: sticks or ripples. AB - CONTEXT: Medical educators internationally are faced with the challenge of teaching and assessing professionalism in their students. Some studies have drawn attention to contextual factors that influence students' responses to professional dilemmas. Although culture is a significant contextual factor, no research has examined student responses to professional dilemmas across different cultures. METHODS: Semi-structured interviews inquiring into reactions towards, and reasoning about, five video clips depicting students facing professional dilemmas were conducted with 24 final-year medical students in Taiwan. The interviews were transcribed and analysed according to the theoretical framework used in prior Canadian studies using the same videos and interview questions. RESULTS: The framework from previous Canadian research, including the components of principles, affect and implications, was generally applicable to the decision making of Taiwanese students, with some distinctions. Taiwanese students cited a few more avowed principles. Taiwanese students emphasised an additional unavowed principle that pertained to following the advice of more senior trainees. In addition to implications for patients, team members or themselves, Taiwanese students considered the impact of their responses on multiple relationships, including those with patients' families and alumni residents. Cultural norms were also cited by Taiwanese students. CONCLUSIONS: Medical educators must acknowledge students' reasoning in professionally challenging situations and guide students to balance considerations of principles, implications, affects and cultural norms. The prominence of Confucian relationalism in this study, exhibited by students' considerations of the rippling effects of their behaviours on all their social relationships, calls for further cross-cultural studies on medical professionalism to move the field beyond a Western individualist focus. PMID- 22324525 TI - Cultural similarities and differences in medical professionalism: a multi-region study. AB - CONTEXT: Over the last two decades, many medical educators have sought to define professionalism. Initial attempts to do so were focused on defining professionalism in a manner that allowed for universal agreement. This quest was later transformed into an effort to 'understand professionalism' as many researchers realised that professionalism is a social construct and is culture sensitive. The determination of cultural differences in the understanding of professionalism, however, has been subject to very little research, possibly because of the practical difficulties of doing so. In this multi-region study, we illustrate the universal and culture-specific aspects of medical professionalism as it is perceived by medical practitioners. METHODS: Forty-six professional attributes were identified by reviewing the literature. A total of 584 medical practitioners, representing the UK, Europe, North America and Asia, participated in a survey in which they indicated the importance of each of these attributes. We determined the 'essentialness' of each attribute in different geographic regions using the content validity index, supplemented with kappa statistics. RESULTS: With acceptable levels of consensus, all regional groups identified 29 attributes as 'essential', thereby indicating the universality of these professional attributes, and six attributes as non-essential. The essentialness of the rest varied by regional group. CONCLUSIONS: This study has helped to identify regional similarities and dissimilarities in understandings of professionalism, most of which can be explained by cultural differences in line with the theories of cultural dimensions and cultural value. However, certain dissonances among regions may well be attributable to socio-economic factors. Some of the responses appear to be counter-cultural and demonstrate practitioners' keenness to overcome cultural barriers in order to provide better patient care. PMID- 22324526 TI - LUCAS: a theoretically informed instrument to assess clinical communication in objective structured clinical examinations. AB - OBJECTIVES: We reviewed papers describing the development of instruments for assessing clinical communication in undergraduate medical students. The instruments had important limitations: most lacked a theoretical basis, and their psychometric properties were often poor or inadequately investigated and reported. We therefore describe the development of a new instrument, the Liverpool Undergraduate Communication Assessment Scale (LUCAS), which is intended to overcome some of these limitations. We designed LUCAS to reflect the theory that communication is contextually dependent, inherently creative and cannot be fully described within a conceptual framework of discrete skills. METHODS: We investigated the preliminary psychometric properties of LUCAS in two studies. To assess construct and external validity, we examined correlations between examiners' LUCAS ratings and simulated patients' ratings of their relationships with students in Year 1 formative (n = 384) and summative (n = 347) objective structured clinical examination (OSCE) samples. Item-total correlations and item difficulty analyses were also performed. The dimensionality of LUCAS was examined by confirmatory factor analysis. We also assessed inter-rater reliability; four raters used LUCAS to rate 40 video-recorded encounters between Year 1 students and simulated patients. RESULTS: Simulated patient ratings correlated with examiner ratings across two OSCE datasets. All items correlated with the total score. Item difficulty showed LUCAS was able to discriminate between student performances. LUCAS had a two-dimensional factor structure: we labelled Factor 1 creative communication and Factor 2 procedural communication. The intraclass correlation coefficient was 0.73 (95% confidence interval 0.54-0.85), indicating acceptable reliability. CONCLUSIONS: We designed LUCAS to move the primary focus of examiners away from an assessment of students' enactment of behavioural skills to a judgement of how well students' communication met patients' needs. LUCAS demonstrated adequate reliability and validity. The instrument can be administered easily and efficiently and is therefore suitable for use in medical school examinations. PMID- 22324527 TI - Reliability estimates: behavioural stations and questionnaires in medical school admissions. AB - CONTEXT: Assessment centres used in evaluating the non-cognitive attributes of medical school candidates must generate scores that reflect as accurate a measurement as possible of these attributes. Thus far, reliability coefficients for such centres have been based on limited samples and individual administrations, without reference to the error of variance that may result from retesting, or from the existence of multiple centres designed to measure the same attributes. METHODS: The National Institute for Testing and Evaluation in Israel has developed and administered two assessment centres: MOR is used by two medical schools and one dental school, and MIRKAM by another medical school. Each centre comprises eight or nine behavioural stations, a standardised biographical questionnaire, and a judgement and decision-making questionnaire. We calculated generalisability coefficients for each centre's eight or nine stations by year, composite reliability coefficients for the overall assessment centres, test retest correlation coefficients for repeaters, and a correlation coefficient between the centres. RESULTS: Between 2006 and 2009, 2662 and 2023 examinees participated in MOR and MIRKAM, respectively; 1479 of these participated in both. The average generalisability coefficients for the stations were 0.69 for MOR and 0.67 for MIRKAM. The composite reliability coefficients for the full centres (behavioural stations plus questionnaires) were 0.79 and 0.76 for MOR and MIRKAM, respectively. The correlations for repeaters, corrected for restriction of range, were 0.59 and 0.43 for MOR and MIRKAM stations, respectively, and 0.72 and 0.65 for the full MOR and MIRKAM assessments, respectively. The correlation between scores on the MOR and MIRKAM stations was 0.56 (0.75 for the overall score). DISCUSSION: The minimal reliability desirable for high-stakes decision making (0.80) was obtained only for 14 or 15 stations with questionnaires. Nevertheless, the values obtained are considerably higher than reliability coefficients for single interviews. The questionnaires contribute significantly to the accuracy of the measurement. These reliability measures constitute an upper threshold for measures of validity. PMID- 22324528 TI - Prevalence of abnormal cases in an image bank affects the learning of radiograph interpretation. AB - OBJECTIVES: Using a large image bank, we systematically examined how the use of different ratios of abnormal to normal cases affects trainee learning. METHODS: This was a prospective, double-blind, randomised, three-arm education trial conducted in six academic training programmes for emergency medicine and paediatric residents in post-licensure years 2-5. We developed a paediatric ankle trauma radiograph case bank. From this bank, we constructed three different 50 case training sets, which varied in their proportions of abnormal cases (30%, 50%, 70%). Levels of difficulty and diagnoses were similar across sets. We randomly assigned residents to complete one of the training sets. Users classified each case as normal or abnormal, specifying the locations of any abnormalities. They received immediate feedback. All participants completed the same 20-case post-test in which 40% of cases were abnormal. We determined participant sensitivity, specificity, likelihood ratio and signal detection parameters. RESULTS: A total of 100 residents completed the study. The groups did not differ in accuracy on the post-test (p = 0.20). However, they showed considerable variation in their sensitivity-specificity trade-off. The group that received a training set with a high proportion of abnormal cases achieved the best sensitivity (0.69, standard deviation [SD] = 0.24), whereas the groups that received training sets with medium and low proportions of abnormal cases demonstrated sensitivities of 0.63 (SD = 0.21) and 0.51 (SD = 0.24), respectively (p < 0.01). Conversely, the group with a low proportion of abnormal cases demonstrated the best specificity (0.83, SD = 0.10) compared with the groups with medium (0.70, SD = 0.15) and high (0.66, SD = 0.17) proportions of abnormal cases (p < 0.001). The group with a low proportion of abnormal cases had the highest false negative rate and missed fractures one-third more often than the groups that trained on higher proportions of abnormal cases. CONCLUSIONS: Manipulating the ratio of abnormal to normal cases in learning banks can have important educational implications. PMID- 22324529 TI - Learning during simulation training is prone to retroactive interference. AB - CONTEXT: Retroactive interference occurs when newly acquired information inhibits recall of previously learned information. This has been shown to influence recall of sounds, tastes and word associations, and is typically seen when learners receive training on one area of content and are then exposed to new content before being evaluated on the original content. Thus far, retroactive interference has received little attention in medical education and has not been studied during simulation training. Our objective was to evaluate whether retroactive interference occurs during simulation training. METHODS: We randomised 167 Year 1 medical students to one of two training protocols. After training on a cardiac murmur, participants were tested either on the same cardiac murmur followed by a novel murmur (the non-interference protocol), or on the novel murmur followed by the training murmur (the interference protocol). We evaluated performance on both murmurs at 1 hour and 6 weeks post-training. RESULTS: We found a significant interaction between training protocol and diagnostic performance on training versus novel murmurs at both testing time points. Students in the non-interference protocol had increased odds of achieving success on the training murmur relative to the novel murmur at 1 hour (odds ratio [OR] 4.96; p < 0.001) and at 6 weeks (OR 4.23; p = 0.001) after training. By comparison, students in the interference protocol did not demonstrate improved performance on the training murmur relative to the novel murmur at either evaluation (1 hour post-training: OR 0.56 [p = 0.08]; 6 weeks post-training: OR 0.66 [p = 0.23]). CONCLUSIONS: Consistent with the theory of retroactive interference, students who encountered a novel murmur between training and evaluation on the murmur on which they had been trained showed no improvement in diagnostic performance following simulation training. These findings should serve to warn educators to consider retroactive interference when designing simulation training sessions. PMID- 22324530 TI - Medical students' understanding of empathy: a phenomenological study. AB - CONTEXT: Empathy towards patients is associated with improved health outcomes. However, quantitative studies using self-reported data have not provided an in depth opportunity to explore the lived experiences of medical students concerning empathy. OBJECTIVES: This study was designed to investigate undergraduate medical students' experiences of the phenomenon of empathy during the course of their medical education and to explore the essence of their empathy. METHODS: This was a descriptive, phenomenological study of medical student interviews conducted using the method of Colaizzi and Giorgi. The sample (n = 10) was drawn from medical students in Years 4 and 5. In-depth interviews were used to obtain a clear understanding of their experiences of empathy in the context of patient care. Interviews continued until no new information could be identified from transcripts. RESULTS: Five themes were identified from analysis: the meaning of empathy; willingness to empathise; innate empathic ability; empathy decline or enhancement, and empathy education. Empathic ability was manifested through two factors: innate capacity for empathy, and barriers to displaying empathy. Different experiences and explanations concerning the decline or enhancement of empathy during medical education were explored. CONCLUSIONS: Empathic ability was identified as an important innate attribute which nevertheless can be enhanced by educational interventions. Barriers to the expression of empathy with patients were identified. Role-modelling by clinical teachers was seen as the most important influence on empathy education for students engaged in experiential learning. PMID- 22324531 TI - The legacy of altruism in health care: the promotion of empathy, prosociality and humanism. AB - OBJECTIVES: This study aimed to examine concepts of altruism and empathy among medical students and professionals in conjunction with health care initiatives designed to support the maintenance of these qualities. METHODS: We searched for the terms 'altruism', 'altruistic', 'helping', 'prosocial behaviour' and 'empathy' in the English-language literature published from 1980 to the present within the Ovid MEDLINE, PsycInfo and PubMed databases. We used conceptual analysis to examine the relationships among altruism, empathy and related prosocial concepts in health care in order to understand how such factors may relate to emotional and career burnout, cynicism, decreased helping and decreased patient-centredness in care. RESULTS: Altruistic ideals and qualities of empathy appear to decrease among some medical students as they progress through their education. During this process, students face increasingly heavy workloads, deal with strenuous demands and become more acquainted with non-humanistic informal practices inherent in the culture of medicine. In combination, these factors increase the likelihood that emotional suppression, detachment from patients, burnout and other negative consequences may result, perhaps as a means of self preservation. Alternatively, by making a mindful and intentional choice to endeavour for self-care and a healthy work-life balance, medical students can uphold humanistic and prosocial attitudes and behaviours. CONCLUSIONS: Promoting altruism in the context of a compensated health care career is contradictory and misguided. Instead, an approach to clinical care that is prosocial and empathic is recommended. Training in mindfulness, self-reflection and emotion skills may help medical students and professionals to recognise, regulate and behaviourally demonstrate empathy within clinical and professional encounters. However, health care initiatives to increase empathy and other humanistic qualities will be limited unless more practical and feasible emotion skills training is offered to and accepted by medical students. Success will be further moderated by the culture of medicine's full acceptance of empathy and humanism into its customs, beliefs, values, interactions and daily practices. PMID- 22324532 TI - Influences on medical students' self-regulated learning after test completion. AB - CONTEXT: The inadequacy of self-assessment as a mechanism to guide performance improvements has placed greater emphasis on the value of testing as a pedagogic strategy. The mechanism whereby testing influences learning is incompletely understood. This study was performed to examine which aspects of a testing experience most influence self-regulated learning behaviour among medical students. METHODS: Sixty-seven medical students participated in a computer-based, multiple-choice test. Initially, participants were instructed to attempt only items for which they felt confident of their response. They were then asked to indicate their best responses to deferred items. Students were then given an opportunity to review the items, with correct responses indicated. Accuracy, the attempt/defer decision and the time taken to reach this decision were recorded, along with participants' ratings of their confidence in each response and the time spent reviewing each item on completion of the test. RESULTS: Students correctly answered a larger proportion of attempted items than deferred items (71% versus 40%; p < 0.001), and indicated a higher mean confidence in responses to items they answered correctly compared with items they answered incorrectly (70 versus 46; p < 0.001). They spent longer reviewing items they had answered incorrectly than correctly (8.3 versus 4.0 seconds; p < 0.001), and paid particular attention to items for which the attempt/defer decision and accuracy were discordant (p < 0.01). The amount of time required to make a decision on whether or not to answer a test question was also related to reviewing time. CONCLUSIONS: Medical students showed a robust ability to accurately and consciously self-monitor their likelihood of success on multiple-choice test items. By focusing their subsequent self-regulated learning on areas in which performance and self-monitoring judgements were misaligned, participants reinforced the importance of providing learners with opportunities to discover the limits of their ability and further elucidated the mechanism through which test-enhanced learning might be derived. PMID- 22324533 TI - Medical education: what the West could learn from Africa. PMID- 22324534 TI - Comments on 'a systematic review of the reliability of objective structured clinical examination scores'. PMID- 22324535 TI - Feasibility of right ventricular longitudinal systolic function evaluation with transthoracic echocardiographic indices derived from tricuspid annular motion: a preliminary study in acute respiratory distress syndrome. AB - INTRODUCTION: Assessment of right ventricular (RV) function in patients with acute respiratory distress syndrome (ARDS) remains challenging. Transthoracic echocardiographic (TTE) indices based on longitudinal systolic RV function are now considered as a reliable evaluation of RV function. We investigated feasibility of two methods in ARDS patients. METHODS: Prospective observational study. TTE was performed after 12-36 hours of mechanical ventilation. Feasibility of tricuspid annular motion (S(t) ), tricuspid annular plane systolic excursion (TAPSE) was compared to usual two-dimensional (2D) study: fractional area change (RV(FAC) ) and ratio of right to left ventricular end-diastolic area (RVEDA/LVEDA). RESULTS: Fifty patients were investigated, with TTE possible in all but two patients. Feasibility was 62% for RV(FAC), 72% for RVEDA/LVEDA, and 96% for TAPSE and S(t). RV dilatation (RVEDA/LVEDA >= 0.60) was found in 16 patients, including 4 patients with acute cor pulmonale. A longitudinal RV dysfunction (TAPSE < 12 mm or S(t) < 11.5 cm/sec) was suspected in 30% of patients. Relation between both longitudinal indices was modest (r(2) = 0.36, P < 0.001). TAPSE (but not S(t) ) was found poorly related to RV(FAC) (r(2) = 0.27, P = 0.03). Both indices were related to LV function (S(t) : r(2) = 0.27, TAPSE: r(2) = 0.17, both P < 0.05). CONCLUSION: Despite a superior feasibility than 2D study, our results suggest that both indices may not bring identical information to echo study. TAPSE may be more adapted to ICU use than S(t) . Both should be further investigated in terms of analysis of RV function and ventricular interdependence. Their relations with LV function may limit their use as sole markers of RV function in this population. PMID- 22324538 TI - Editorial: Consensus on CAM methods for nursing research? PMID- 22324539 TI - Editorial: Location, location, location - the position of authors in scholarly publishing. PMID- 22324540 TI - Second-level hospital health professionals' attitudes to lesbian, gay, bisexual and transgender parents seeking health for their children. AB - AIM: The aim of the study was to assess health professionals' knowledge, attitudes and beliefs regarding lesbian, gay, bisexual and transgender parents accessing health care for their children. BACKGROUND: Lesbian, gay, bisexual and transgender parents can be reluctant to reveal their sexual orientation to health professionals, and consequently, they may not receive adequate or timely provision of health care. Currently, there is little research in this area. DESIGN: Descriptive, comparative study of 86 health professionals using a cross sectional survey design with a set of validated, anonymous questionnaires. METHOD: Associations between variables were assessed using chi-squared tests of independence, and differences between groups were assessed using the Mann-Whitney U-test or the Kruskal-Wallis one-way analysis of variance test. Content analysis was used to examine responses to open-ended questions. RESULTS: Knowledge and attitude scores were significantly associated with race, religious beliefs, frequency of attendance at religious services and having a friend who is openly lesbian, gay, bisexual and transgender. CONCLUSIONS: Information gained from this study will assist clinicians and hospital management to develop policies and practices that ensure lesbian, gay, bisexual and transgender families receive equitable, high-quality and holistic health care. RELEVANCE TO CLINICAL PRACTICE: Properly implemented family-centred care is an ideal model to provide care for lesbian, gay, bisexual and transgender families. However, the benefits of family centred care can only be realised fully if health professionals delivering that care are sensitive to the context, functions and constructs of all the families they encounter. PMID- 22324541 TI - Quality indicators for care of cancer patients in their last days of life: literature update and experts' evaluation. AB - BACKGROUND: Quality indicators (QIs) are needed to monitor and to improve palliative care. Care of patients in the last days of life is a discrete phase of palliative care and therefore specific QIs are needed. This study aimed to identify and evaluate current QIs against which to measure future care of patients in the last days of life. METHODS: To identify QIs for patients in the last days of life an update of the literature and national guidelines was conducted. Subsequently, an international panel of palliative care experts was asked to evaluate the identified QIs: how well they describe care and how applicable they are for care in the last days of life. Also additional QIs were asked. RESULTS: In total, 34 QIs for care in the last days were identified in the literature and guidelines. The experts (response rate 58%) agreed with seven QIs as being good descriptors and applicable: concerning a home visit for the family following a patient's death, the presence of a dedicated family room, limited patients receiving chemotherapy, limited need for pain control, gastrointestinal symptoms, and communication from professional to patient and family. The experts also suggested 18 additional topics for QIs for the last days of life. CONCLUSION: Currently no definite set of QIs exist to describe quality of care of patients in their last days of life. New QIs that are focused on care for patients in their last days of life, their relatives, as well as their professional caregivers are needed. PMID- 22324542 TI - Characterization of cerebral glucose dynamics in vivo with a four-state conformational model of transport at the blood-brain barrier. AB - Determination of brain glucose transport kinetics in vivo at steady-state typically does not allow distinguishing apparent maximum transport rate (T(max)) from cerebral consumption rate. Using a four-state conformational model of glucose transport, we show that simultaneous dynamic measurement of brain and plasma glucose concentrations provide enough information for independent and reliable determination of the two rates. In addition, although dynamic glucose homeostasis can be described with a reversible Michaelis-Menten model, which is implicit to the large iso-inhibition constant (K(ii)) relative to physiological brain glucose content, we found that the apparent affinity constant (K(t)) was better determined with the four-state conformational model of glucose transport than with any of the other models tested. Furthermore, we confirmed the utility of the present method to determine glucose transport and consumption by analysing the modulation of both glucose transport and consumption by anaesthesia conditions that modify cerebral activity. In particular, deep thiopental anaesthesia caused a significant reduction of both T(max) and cerebral metabolic rate for glucose consumption. In conclusion, dynamic measurement of brain glucose in vivo in function of plasma glucose allows robust determination of both glucose uptake and consumption kinetics. PMID- 22324543 TI - Targeting of primary breast cancers and metastases in a transgenic mouse model using rationally designed multifunctional SPIONs. AB - Breast cancer remains one of the most prevalent and lethal malignancies in women. The inability to diagnose small volume metastases early has limited effective treatment of stage 4 breast cancer. Here we report the rational development and use of a multifunctional superparamagnetic iron oxide nanoparticle (SPION) for targeting metastatic breast cancer in a transgenic mouse model and imaging with magnetic resonance (MR). SPIONs coated with a copolymer of chitosan and polyethylene glycol (PEG) were labeled with a fluorescent dye for optical detection and conjugated with a monoclonal antibody against the neu receptor (NP neu). SPIONs labeled with mouse IgG were used as a nontargeting control (NP-IgG). These SPIONs had desirable physiochemical properties for in vivo applications such as near neutral zeta potential and hydrodynamic size around 40 nm and were highly stable in serum containing medium. Only NP-neu showed high uptake in neu expressing mouse mammary carcinoma (MMC) cells which was reversed by competing free neu antibody, indicating their specificity to the neu antigen. In vivo, NP neu was able to tag primary breast tumors and significantly, only NP-neu bound to spontaneous liver, lung, and bone marrow metastases in a transgenic mouse model of metastatic breast cancer, highlighting the necessity of targeting for delivery to metastatic disease. The SPIONs provided significant contrast enhancement in MR images of primary breast tumors; thus, they have the potential for MRI detection of micrometastases and provide an excellent platform for further development of an efficient metastatic breast cancer therapy. PMID- 22324544 TI - Contribution of several volatile phenols and their glycoconjugates to smoke related sensory properties of red wine. AB - Guaiacol and 4-methylguaiacol are well-known as contributors to the flavor of wines made from smoke-affected grapes, but there are other volatile phenols commonly found in smoke from forest fires that are also potentially important. The relationships between the concentration of a range of volatile phenols and their glycoconjugates with the sensory characteristics of wines and model wines were investigated. Modeling of the attribute ratings from a sensory descriptive analysis of smoke-affected wines with their chemical composition indicated the concentrations of guaiacol, o-cresol, m-cresol, and p-cresol were related to smoky attributes. The best-estimate odor thresholds of these compounds were determined in red wine, together with the flavor threshold of guaiacol. Guaiacol beta-D-glucoside and m-cresol beta-D-glucoside in model wine were found to give rise to a smoky/ashy flavor in-mouth, and the respective free volatiles were released. The study indicated that a combination of volatile phenols and their glycosides produces an undesirable smoke flavor in affected wines. The observation of flavor generation from nonvolatile glycoconjugates in-mouth has potentially important implications. PMID- 22324545 TI - Are polymorphisms in oestrogen receptors genes associated with lipid levels in response to hormone therapy? AB - BACKGROUND: Polymorphisms in the oestrogen receptor 1 (ESR1) and oestrogen receptor 2 (ESR2) genes are associated with intermediate or endpoint markers of cardiovascular disease and with the efficacy of postmenopausal hormone therapy (HT). Contradictory findings have been described in the past and the role of these genetics variants remains unclear. METHODS: A cross-sectional study was carried out with 266 postmenopausal women, of whom 115 received oral HT (HT+) and 151 did not receive any HT (HT-). We analysed three single-nucleotide polymorphisms (SNPs) in ESR1 (rs1801132, rs7757956 and rs2813544) and two in ESR2 (rs3020450 and rs7154455) and derived haplotypes with three additional polymorphisms that had been previously investigated by our group (ESR1 rs2234693 and ESR2 rs1256049 and rs4986938). RESULTS: The ESR1 rs2813544 polymorphism was associated with low-density lipoprotein cholesterol (LDL-C) in HT+ postmenopausal women (p = 0.044; pC = 0.388), while one ESR2 gene haplotype was associated with total cholesterol (T-chol) (p = 0.015; pC = 0.090) and LDL-C in HT+ postmenopausal women (p = 0.021; pC = 0.126). CONCLUSION: Our findings suggest that, in HT+ postmenopausal women, the rs2813544 polymorphism may influence LDL-C levels and, as previously described, ESR2 rs1256049 is associated with T-chol and LDL-C. No previous study has investigated the association of this SNP set with lipoprotein levels in women while taking into account the hormonal status of the patients. PMID- 22324546 TI - Synthesis and evaluation of sulfonylnitrophenylthiazoles (SNPTs) as thyroid hormone receptor-coactivator interaction inhibitors. AB - We previously identified a series of methylsulfonylnitrobenzoates (MSNBs) that block the interaction of the thyroid hormone receptor with its coactivators. MSNBs inhibit coactivator binding through irreversible modification of cysteine 298 of the thyroid hormone receptor (TR). Although MSNBs have better pharmacological features than our first generation inhibitors (beta aminoketones), they contain a potentially unstable ester linkage. Here we report the bioisosteric replacement of the ester linkage with a thiazole moiety, yielding sulfonylnitrophenylthiazoles (SNPTs). An array of SNPTs representing optimal side chains from the MSNB series was constructed using parallel chemistry and evaluated to test their antagonism of the TR-coactivator interaction. Selected active compounds were evaluated in secondary confirmatory assays including regulation of thyroid response element driven transcription in reporter constructs and native genes. In addition the selected SNPTs were shown to be selective for TR relative to other nuclear hormone receptors (NRs). PMID- 22324547 TI - Prevalence of metabolic syndrome components among the elderly using three different definitions: a cohort study in Finland. AB - OBJECTIVE: Limited data are available on the metabolic syndrome (MetS) and its components in elderly people (aged 70 years and over) at population level in Northern Europe. A study was undertaken to investigate the prevalence of MetS and its components in an aging population by using different definitions. DESIGN, SETTING, AND SUBJECTS: A cross-sectional study of 539 inhabitants from Northern Finland (mean age 71.9 years) was conducted to investigate the prevalence of MetS, by using the definitions of MetS by the National Cholesterol Education Panel (NCEP), the modified NCEP (NCEPm), and the International Diabetes Federation (IDF). MAIN OUTCOME MEASURES: Prevalence of MetS by the NCEP, NCEP modified, and IDF criteria. RESULTS: Overall, the prevalence of MetS was 24.7%, 35.2%, and 37.2% in men, by NCEP, modified NCEP, and IDF-definitions, respectively. In women the corresponding figures were 20.9%, 33.1%, and 47.8%. Hypertension was the most common component in both men (91.8%) and women (89.0%) by the IDF criteria. Glucose abnormalities were particularly prevalent in men (53.2% by NCEP and 78.4% by IDF criteria). CONCLUSIONS: The most common component was hypertension in both genders. Lower waist-circumference cut-off points of the IDF criteria led to a higher prevalence of MetS particularly in women. Prevalence of MetS varied significantly when measured by different definitions. Nearly half of older women met the IDF definition of MetS, which was more than twofold when compared with NCEP. Clinical practitioners should be aware of the limitations when using set criteria of MetS, in contrast to identifying the individual cardiovascular risk factors and the accumulation of these. PMID- 22324549 TI - Synthesis and optoelectronic properties of two-dimensional FeS2 nanoplates. AB - There is a growing interest in the earth abundant and nontoxic iron disulfide (FeS(2)) photovoltaic materials. Here, we report the synthesis of FeS(2) nanoplates with different spectral features which we have associated with thicknesses and crystallization. The structure and crystalline order of ultrathin FeS(2) nanoplates have a strong influence on the carrier lifetime, electronic and optical properties. We demonstrate that two-dimensional FeS(2) nanoplates show great promise for fabrication of hybrid bulk heterojunction solar cells. This opens up a host of applications of these materials as inexpensive solar cells and photocatalysts. PMID- 22324550 TI - Neuropeptide Y-induced phase shifts of PER2::LUC rhythms are mediated by long term suppression of neuronal excitability in a phase-specific manner. AB - Endogenous circadian rhythms are entrained to the 24-h light/dark cycle by both light and nonphotic stimuli. During the day, nonphotic stimuli, such as novel wheel-induced exercise, produce large phase advances. Neuropeptide Y (NPY) release from the thalamus onto suprachiasmatic nucleus (SCN) neurons at least partially mediates this nonphotic signal. The authors examined the hypothesis that NPY-induced phase advances are accompanied by suppression of PER2 and are mediated by long-term depression of neuronal excitability in a phase-specific manner. First, it was found that NPY-induced phase advances in PER2::LUC SCN cultures are largest when NPY (2.35 uM) is given in the early part of the day (circadian time [CT] 0-6). In addition, PER2::LUC levels in NPY-treated (compared to vehicle-treated) samples were suppressed beginning 6-7 h after treatment. Similar NPY application to organotypic Per1::GFP SCN cultures resulted in long term suppression of spike rate of green fluorescent protein-positive (GFP+) cells when slices were treated with NPY during the early or middle of the day (zeitgeber time [ZT] 2 or 6), but not during the late day (ZT 10). Furthermore, 1 h bath application of NPY to acute SCN brain slices decreased general neuronal activity measured through extracellular recordings. Finally, NPY-induced phase advances of PER2::LUC rhythms were blocked by latent depolarization with 34.5 mM K(+) 3 h after NPY application. These results suggest that NPY-induced phase advances may be mediated by long-term depression of neuronal excitability. This model is consistent with findings in other brain regions that NPY-induced persistent hyperpolarization underlies mechanisms of energy homeostasis, anxiety related behavior, and thalamocortical synchronous firing. PMID- 22324551 TI - DNA microarray analysis and functional profile of pituitary transcriptome under core-clock protein BMAL1 control. AB - Although it is known to contain five cell types that synthesize and release hormones with a circadian pattern, the pituitary gland is poorly characterized as a circadian oscillator. By a differential microarray analysis, 252 genes were found to be differentially expressed in pituitaries from Bmal1(-/-) knockout versus wild-type mice. By integrative analyses of the data set with the Annotation, Visualization, and Integrated Discovery (DAVID) Bioinformatics Resources annotation analysis system, pituitary genes with altered expression in Bmal1(-/-) mice were dispatched among functional categories. Clusters of genes related to signaling and rhythmic processes as well as transcription regulators, in general, were found enriched in the data set, as were pathways such as circadian rhythm, transforming growth factor beta (TGFbeta) signaling, valine, leucine, and isoleucine degradation, and peroxisome proliferator-activated receptor (PPAR) signaling pathways. Gene Ontology term overrepresentation analyses revealed significant enrichment for genes involved in 10 key biological processes. To determine whether genes with altered expression in Bmal1(-/-) mice were actually circadian genes, we further characterized in the mouse pituitary gland the daily pattern of some of these genes, including core-clock genes. Core clock genes and genes selected from three identified overrepresented biological processes, namely, hormone metabolic process, regulation of transcription from RNA polymerase II promoter, and cell adhesion, displayed a rhythmic pattern. Given the enrichment in genes dedicated to cell adhesion and their daily changes in the pituitary, it is hypothesized that cell-cell interactions could be involved in the transmission of information between endocrine cells, allowing rhythmic hormone outputs to be controlled in a temporally precise manner. PMID- 22324552 TI - Sleep, diurnal preference, health, and psychological well-being: a prospective single-allelic-variation study. AB - Individual differences in sleep and diurnal preference associate with physical and mental health characteristics, but few genetic determinants of these differences have been identified. A variable number tandem repeat (VNTR) polymorphism in the PERIOD3 (PER3) gene (rs57875989) has been reported to associate with diurnal preference, i.e., preferred timing of waking and sleep. Here, the authors investigate in a prospective single-candidate genetic variant study whether allelic variation for this polymorphism associates also with reported actual sleep timing and sleep duration, as well as psychological and health measures. Six hundred and seventy-five subjects, aged 20 to 35 yrs, completed questionnaires to assess sleep and psychological and health characteristics and were genotyped for the PER3 VNTR. Homozygosity for the longer allele (PER3(5/5)) of the VNTR was associated with increased morning preference, earlier wake time and bedtime, and reduced daytime sleepiness. Separate analyses of work and rest days demonstrated that the increase in time in bed during rest days was greatest in PER3(5/5) homozygotes. PER3 genotype modified the effects of sleep timing and duration on fluid intelligence and body mass index. Genotype was not associated with physical or psychological characteristics as assessed by the SF-36 Health Questionnaire, the General Health Questionnaire, the Big Five Inventory, the Behavioral Inhibition System-Behavioral Activation System scales, and the Positive and Negative Affect Scale, even though these measures varied significantly with diurnal preference as assessed by the Morningness-Eveningness Questionnaire. Whereas diurnal preference also predicts mental health and psychological characteristics, as well as sleep timing, the PER3 VNTR specifically affects measures of sleep timing and may also modify the effects of sleep on health outcome measures. PMID- 22324553 TI - Circadian dysfunction in a rotenone-induced parkinsonian rodent model. AB - Parkinson's disease (PD) is a neurodegenerative disorder that also involves circadian rhythm alterations. Modifications of circadian rhythm parameters have been shown to occur in both PD patients and toxin-induced PD animal models. In the latter case, rotenone, a potent inhibitor of mitochondrial complex I (nicotinamide adenine dinucleotide [NADH]-quinone reductase), has been used to elicit degeneration of dopaminergic neurons and development of parkinsonian syndrome. The present work addresses alterations induced by rotenone on both locomotor and body temperature circadian rhythms in rats. Rotenone-treated rats exhibited abnormalities in equilibrium, postural instability, and involuntary movements. Long-term subcutaneous administration of rotenone significantly reduced mean daily locomotor activity in most animals. During rotenone administration, mean body temperatures (BTs) and BT rhythm amplitudes were significantly lower than those observed in the control group. After long-term rotenone administration, the circadian rhythms of both locomotor activity (LA) and BT displayed decreased amplitudes, lower interdaily phase stability, and higher rhythm fragmentation, as compared to the control rats. The magnitude of the LA and BT circadian rhythm alterations induced by rotenone positively correlated with degree of motor impairment. These results indicate that rotenone induces circadian dysfunction in rats through some of the same mechanisms as those responsible for the development of motor disturbances. PMID- 22324554 TI - Paradoxical masking effects of bright photophase and high temperature in Drosophila malerkotliana. AB - Synergic contribution of light and temperature is known to cause a paradoxical masking effect (inhibition of activity by bright light and high temperature) on various rhythms of animals. The present study reports the paradoxical masking effects of 1000-lux photophase at 25 degrees C on the locomotor activity rhythm of Drosophila malerkotliana. Flies were subjected to light (L)-dark (D) 12:12 cycles wherein the photophase was varied from 10 to 1000 lux, whereas the scotophase was set to 0 lux in these and subsequent LD cycles. At 10, 100, and 500 lux, the flies were diurnal; however, at 1000 lux they were nocturnal. Transfer from LD 12:12 cycles to continuous darkness (DD) initiated free-running rhythmicity in all flies. Free-running rhythms of the flies switched from the 10 lux to the 500-lux groups started from the last activity-onset phase of the rhythm following 3-5 transient cycles, suggesting involvement of the circadian pacemaker. In contrast, the free-running rhythm of the flies of the 1000-lux group began abruptly from the last lights-on phase of the LD cycle, indicating noninvolvement of the pacemaker. Furthermore, all flies showed nocturnal activity in the two types of LD 12:12 cycles when the photophase was 1000 lux. The first type of LD cycles had three succeeding photophases of 100, 1000, and again 100 lux, whereas the second type of LD cycles had only one photophase of 1000 lux, but the LD 12:12 cycles were reversed to DL 12:12 cycles. Apparently, the combined effects of light and temperature caused such paradoxical masking effects. This hypothesis was tested by repeating the above experiments at 20 degrees C. Flies in all experiments exhibited a diurnal activity pattern, even when the photophase was 1000 lux. Thus, the present study demonstrates that the paradoxical masking effect in D. malerkotliana was caused by the additive influence of light intensity and temperature. This strategy appears to have physiological significance, i.e., to shun and thus protect against the bright photophase at high temperature in the field. PMID- 22324555 TI - Towards a characterization of the locomotor activity rhythm of the supralittoral isopod Tylos europaeus. AB - Freshly collected samples of Tylos europaeus from Korba beach (northeast of Tunisia) were housed in an environmental cabinet at controlled temperature (18 degrees C +/- .5 degrees C) and photoperiod. Locomotor activity was recorded under two photoperiodic regimens by infrared actography every 20 min by multichannel data loggers. One regimen simulated the natural light-dark cycle on the day of collection, whereas the second imposed a state of continuous darkness on all individuals. Under entraining conditions, the animals displayed rhythmic activity, in phase with the period of darkness, whereas in continuous darkness these isopods exhibited a strong endogenous rhythm with circadian and semidiurnal components at mean periods of tau (h:min) = 25:09 +/- 01:02 h and tau = 12:32 +/- 00:26 h, respectively. Under free-running conditions, this endogenous rhythm showed significant intraspecific variability. PMID- 22324556 TI - Influence of altered photoperiods on serum melatonin and its receptors (MT1 and MT2) in the brain, retina, and ovary in carp Catla catla. AB - Daily variation in melatonin receptor (MT1 and MT2) density in three specific tissues-brain, retina, and ovary-and its temporal relationship with serum melatonin were evaluated for the first time in a freshwater teleost, the carp Catla catla, under natural as well as altered photoperiods in different reproductive phases of the annual cycle. Cosinor analysis was used to determine rhythmic features of the serum melatonin and receptors (MT1 and MT2) in different tissues. In each photoperiodic group, irrespective of season, the daily minimum serum melatonin level was noted at midday. However, the daily peak value of melatonin varied in relation to both photo-schedules and reproductive phases. Under natural photoperiods (NPs; duration varied with seasons) and short photoperiods (SPs; light [L]:dark [D] 8:16), it occurred in the late dark phase during the preparatory phase, and at midnight in the remaining parts of the annual cycle. On the other hand, in each reproductive phase, compared to corresponding NP carp, the daily melatonin peak under long photoperiods (LPs; L:D 16:8) exhibited a phase delay of ~2-3 h (occurring during the late dark phase). The melatonin levels at each sampling point were highest during the postspawning phase and lowest during the spawning phase, irrespective of the photoperiodic history of the fish. In each tissue, Western blot analysis revealed a band at ~37 kDa and a band at ~36 kDa corresponding to the molecular weights of native MT1 and MT2 receptor proteins, respectively, with the band intensity of MT1 always being higher than that of a 36-kDa protein. The content of both melatonin receptor proteins varied significantly according to the studied tissue (being highest in the retina, intermediate in the brain, and lowest in the ovary), time in the daily cycle (peak at midnight and fall at midday), and reproductive phase in the annual cycle (highest in the spawning phase and lowest in the postspawning phase). Remarkably, no significant effects of altered photoperiod were detected on any rhythm parameters of either MT1 or MT2 in any of the studied tissues. Collectively, the results of the present study suggest a role of photoperiod in determining daily and seasonal profiles of serum melatonin, but not its receptor proteins, on the ovary or on any nongonad tissues in carp. PMID- 22324557 TI - Melatonin receptor expression in the zebra finch brain and peripheral tissues. AB - The circadian endocrine hormone melatonin plays a significant role in many physiological processes, such as modulating the sleep/wake cycle and oxidative stress. Melatonin is synthesized and secreted during the night by the pineal gland and released into the circulatory system. It binds to numerous membrane, cytosolic, and nuclear receptors in the brain and peripheral organs. Three G protein-linked membrane receptors (Mel1A, Mel1B, and Mel1C) have been identified in numerous species. Considering the importance of this hormone and its receptors, this study looks at the location and rhythmicity of these three avian melatonin receptors using reverse transcriptase-polymerase chain reaction (RT PCR) mRNA analysis techniques. This study shows successful partial cloning of the three receptors, and gene expression analysis reveals significant rhythms of the Mel1A receptor in the cerebellum, diencephalon, tectum opticum, telencephalon, and retina. Significant rhythms were found in the diencephalon, pineal gland, retina, tectum opticum, and cerebellum of the Mel1B receptor, whereas Mel1C appeared not to be rhythmically expressed in brain tissues studied. Mel1A, Mel1B, and Mel1C receptor mRNAs were also present in peripheral tissues, showing tissue specific expression patterns. PMID- 22324558 TI - Melatonin production and light exposure of rotating night workers. AB - Decreased melatonin production, due to acute suppression of pineal melatonin secretion by light exposure during night work, has been suggested to underlie higher cancer risks associated with prolonged experience of night work. However, the association between light exposure and melatonin production has never been measured in the field. In this study, 24-h melatonin production and ambulatory light exposure were assessed during both night-shift and day/evening-shift periods in 13 full-time rotating shiftworkers. Melatonin production was estimated with the excretion of urinary 6-sulfatoxymelatonin (aMT6s), and light exposure was measured with an ambulatory photometer. There was no difference in total 24-h aMT6s excretion between the two work periods. The night-shift period was characterized by a desynchrony between melatonin and sleep-wake rhythms, as shown by higher melatonin production during work and lower melatonin production during sleep when working night shifts than when working day/evening shifts. Light exposure during night work showed no correlation with aMT6s excreted during the night of work (p > .5), or with the difference in 24-h aMT6s excretion between the two work periods (p > .1). However, light exposure during night work was negatively correlated with total 24-h aMT6s excretion over the entire night-shift period (p < .01). In conclusion, there was no evidence of direct melatonin suppression during night work in this population. However, higher levels of light exposure during night work may have decreased total melatonin production, possibly by initiating re-entrainment and causing internal desynchrony. This interpretation is consistent with the proposition that circadian disruption, of which decreased melatonin production is only one of the adverse consequences, could be the mediator between night shiftwork and cancer risks. PMID- 22324559 TI - Sleep, sleepiness, fatigue, and performance of 12-hour-shift nurses. AB - Nurses working 12-h shifts complain of fatigue and insufficient/poor-quality sleep. Objectively measured sleep times have not been often reported. This study describes sleep, sleepiness, fatigue, and neurobehavioral performance over three consecutive 12-h (day and night) shifts for hospital registered nurses. Sleep (actigraphy), sleepiness (Karolinska Sleepiness Scale [KSS]), and vigilance (Performance Vigilance Task [PVT]), were measured serially in 80 registered nurses (RNs). Occupational fatigue (Occupational Fatigue Exhaustion Recovery Scale [OFER]) was assessed at baseline. Sleep was short (mean 5.5 h) between shifts, with little difference between day shift (5.7 h) and night shift (5.4 h). Sleepiness scores were low overall (3 on a 1-9 scale, with higher score indicating greater sleepiness), with 45% of nurses having high level of sleepiness (score > 7) on at least one shift. Nurses were progressively sleepier each shift, and night nurses were sleepier toward the end of the shift compared to the beginning. There was extensive caffeine use, presumably to preserve or improve alertness. Fatigue was high in one-third of nurses, with intershift fatigue (not feeling recovered from previous shift at the start of the next shift) being most prominent. There were no statistically significant differences in mean reaction time between day/night shift, consecutive work shift, and time into shift. Lapsing was traitlike, with rare (39% of sample), moderate (53%), and frequent (8%) lapsers. Nurses accrue a considerable sleep debt while working successive 12-h shifts with accompanying fatigue and sleepiness. Certain nurses appear more vulnerable to sleep loss than others, as measured by attention lapses. PMID- 22324560 TI - Individual traits and environmental factors influencing sleep timing: a study of 225 Japanese couples. AB - Behavioral and physiological processes, such as sleep-wakefulness, thermoregulation, and hormone secretion, exhibit 24-h rhythms in most organisms. These biological rhythms are driven by the circadian clock system and are entrained by the external environment, which in the case of humans includes social time schedules. Couples might be ideal experimental subjects to discriminate between individual traits and environmental factors, as they share lifestyle habits but not genetic backgrounds. In this study, sleep timing was compared between married Japanese couples (n = 225) who had lived together for 1 yr or more (mean 17 yrs). Additionally, the authors evaluated the influence of individual traits and environmental factors on an individual's sleep timing per each couple. The results reveal that the sleep timings of a couple are mainly associated with the chronotypes of the husband and wife, whereas the sleep timings are significantly influenced by certain environmental factors. The findings suggest that chronotype remains one of the major determinants of an individual's sleep onset and wake times. Understanding an individual's chronotype may help improve the quality of life issues surrounding sleep. PMID- 22324561 TI - A systematic review of the literature on the treatment of pityriasis rubra pilaris type 1 with TNF-antagonists. AB - BACKGROUND: Adult pityriasis rubra pilaris (PRP) type 1 is a rare chronic papulosquamous disorder with clinical and histological parallels with psoriasis. Treatment is challenging and recent case reports suggest a potential role for tumour necrosis factor (TNF) antagonists. OBJECTIVES: Our objective was to systematically review the literature for evidence of efficacy of TNF antagonists in the treatment of adult PRP. METHODS: We performed a systematic search of the Cochrane library, EMBASE, Pubmed and MEDLINE databases. We defined diagnosis of PRP, classified clinical response and whether this was clearly attributed to TNF antagonists. We also reviewed disease, treatment duration and follow up. RESULTS: Sixteen articles were selected for detailed review. From these, 12 articles (13 cases) met our predefined criteria and were included in the systematic review. The authors identified two more cases from their personal archive. A total of 15 evaluable cases were included for analysis. Twelve showed complete response (CR) (80%) to TNF-antagonists with a mean time to maximal response of 5 months. In 10 of the CR cases (83%) this was clearly attributable to TNF antagonist therapy. CONCLUSION: These data indicate that TNF-antagonists may be of value in treating adult type 1 PRP refractory to other systemic agents but selective reporting bias, together with the lack of standard diagnostic criteria and established spontaneous resolution in PRP, prevent any firm recommendations on their place in management. PMID- 22324562 TI - Personal and environmental factors contributing to participation in romantic relationships and sexual activity of young adults with cerebral palsy. AB - PURPOSE: To study determinants of romantic relationships and sexual activity of young adults with cerebral palsy (CP), focusing on personal and environmental factors. METHOD: A cohort study was performed with 74 young adults (46 men; 28 women) aged 20-25 years (SD 1.4) with CP (49% unilateral CP, 76% GMFCS level I, 85% MACS level I). All participants were of normal intelligence. Romantic relationships, sexual activity (outcome measures), personal and environmental factors (associated factors) were assessed. Associations were analyzed using logistic regression analyses. RESULTS: More females than males with CP were in a current romantic relationship. Self-esteem, sexual esteem and feelings of competence regarding self-efficacy contributed positively to having current romantic relationships. A negative parenting style contributed negatively. Age and gross motor functioning explained 20% of the variance in experience with intercourse. In addition, sexual esteem and taking initiative contributed significantly to intercourse experience. CONCLUSIONS: For young adults with CP personal factors (20-35% explained variances) seem to contribute more than environmental factors (9-12% explained variances) to current romantic relationships and sexual experiences. We advice parents and professionals to focus on self-efficacy, self-esteem and sexual self-esteem in development of young adults with CP. [ IMPLICATIONS FOR REHABILITATION: * The severity of gross motor functioning contributed somewhat to sexual activities, but not to romantic relationships.* High self-efficacy, self-esteem and sexual self-esteem can facilitate involvement in romantic and sexual relationships for young adults with CP.] PMID- 22324563 TI - Roy's safety-first portfolio principle in financial risk management of disastrous events. AB - Roy pioneers the concept and practice of risk management of disastrous events via his safety-first principle for portfolio selection. More specifically, his safety first principle advocates an optimal portfolio strategy generated from minimizing the disaster probability, while subject to the budget constraint and the mean constraint that the expected final wealth is not less than a preselected disaster level. This article studies the dynamic safety-first principle in continuous time and its application in asset and liability management. We reveal that the distortion resulting from dropping the mean constraint, as a common practice to approximate the original Roy's setting, either leads to a trivial case or changes the problem nature completely to a target-reaching problem, which produces a highly leveraged trading strategy. Recognizing the ill-posed nature of the corresponding Lagrangian method when retaining the mean constraint, we invoke a wisdom observed from a limited funding-level regulation of pension funds and modify the original safety-first formulation accordingly by imposing an upper bound on the funding level. This model revision enables us to solve completely the safety-first asset-liability problem by a martingale approach and to derive an optimal policy that follows faithfully the spirit of the safety-first principle and demonstrates a prominent nature of fighting for the best and preventing disaster from happening. PMID- 22324564 TI - Cerebral blood flow and freezing of gait in Parkinson's disease. AB - OBJECTIVE: We investigated the relationship between freezing of gait (FOG) severity in Parkinson's disease (PD) and regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT) and evaluated the effect of selegiline therapy. METHOD: We evaluated 54 patients with PD (FOG positive: 21 patients, and FOG negative: 33 patients) with N-isopropyl-p-[I-123] iodoamphetamine ((123) I-IMP) SPECT and the Unified Parkinson's Disease Rating Scale (UPDRS) part III, Mini-Mental State Examination (MMSE), and Beck Depression Inventory. [Correction added on 18 April 2012, after online publication: In the preceding statement, 55 instead of 54 patients with PD were evaluated, and FOG negative consisted of 34 instead of 33 patients] Furthermore, we examined rCBF in FOG-negative patients treated with levodopa with or without selegiline. RESULTS: Z-values of bilateral Brodmann areas (BA) 10 and 11 and left BA32 showed significant increases in the FOG-positive group compared with the FOG-negative group. [Correction added on 18 April 2012, after online publication: In the preceding statement, Z-values was changed to Z-scores] There were significantly positive correlations between Z-values of these areas and FOG score, especially on both sides of BA11. [Correction added on 18 April 2012, after online publication: In the preceding statement, Z-values was changed to Z-scores] An increase in Z-values in bilateral BA10 and 11 and left BA32 in the levodopa selegiline treatment group after 1 year was significantly inhibited compared with the levodopa treatment group. [Correction added on 18 April 2012, after online publication: In the preceding statement, left BA32 was changed to right BA32, and Z-values was changed to Z-scores] CONCLUSION: There was a close relationship between FOG severity in PD and an increase in rCBF in BA 10, 11 and 32. Furthermore, selegiline's FOG prevention effect may be related to maintaining rCBF in these same areas. PMID- 22324565 TI - Does session attendance by a supportive significant other predict outcomes in individual treatment for alcohol use disorders? AB - BACKGROUND: A significant amount of research has supported the efficacy of couple versus individual treatment for alcohol use disorders, yet little is known about whether involving a significant other during the course of individual treatment can improve outcomes. Likewise, several barriers to couple treatment exist and a more flexible approach to significant other involvement may be warranted. METHODS: This study constituted secondary analyses of the COMBINE data, a randomized clinical trial that combined pharmacotherapy and behavioral intervention for alcohol dependence. Data were drawn from the 16-week individual combined behavioral intervention (CBI), which had 776 participants, 31% of which were female, and 23% were non-white. The current study examined whether attendance by a supportive significant other (SSO) during CBI sessions would predict better outcomes. It was further hypothesized that active SSO involvement, defined by attendance during drink refusal or communication skills training sessions, would predict better outcomes. RESULTS: SSOs attended at least 1 session for 26.9% of clients. Clients with SSOs who attended at least 1 session had significantly fewer drinking days and fewer drinking-related problems at the end of treatment. The presence of an SSO during a drink refusal training session predicted significantly better outcomes, as compared to SSO attendance at other sessions and drink refusal training without an SSO present. SSO attendance at a communication training session did not predict better outcomes. CONCLUSIONS: These results suggest that specific types of active involvement may be important for SSO-involved treatment to have greater efficacy than individual treatment. PMID- 22324566 TI - Towards commercial scale postcombustion capture of CO2 with monoethanolamine solvent: key considerations for solvent management and environmental impacts. AB - Chemical absorption with aqueous amine solvents is the most advanced technology for postcombustion capture (PCC) of CO(2) from coal-fired power stations and a number of pilot scale programs are evaluating novel solvents, optimizing energy efficiency, and validating engineering models. This review demonstrates that the development of commercial scale PCC also requires effective solvent management guidelines to ensure minimization of potential technical and environmental risks. Furthermore, the review reveals that while solvent degradation has been identified as a key source of solvent consumption in laboratory scale studies, it has not been validated at pilot scale. Yet this is crucial as solvent degradation products, such as organic acids, can increase corrosivity and reduce the CO(2) absorption capacity of the solvent. It also highlights the need for the development of corrosion and solvent reclamation technologies, as well as strategies to minimize emissions of solvent and degradation products, such as ammonia, aldehydes, nitrosamines and nitramines, to the atmosphere from commercial scale PCC. Inevitably, responsible management of aqueous and solid waste will require more serious consideration. This will ultimately require effective waste management practices validated at pilot scale to minimize the likelihood of adverse human and environmental impacts from commercial scale PCC. PMID- 22324567 TI - Improving the culture of patient safety through the Magnet(r) journey. AB - This article outlines how one academic medical center's nursing service has developed programs to improve patient safety and quality outcomes through the use of the Magnet Re-Designation Accreditation Process(R) and a shared governance model. Successful programs have been implemented across the continuum of care. These programs include educational initiatives that increased both the number of nurses with BSN degrees and specialty certifications and also the number of patient-focused initiatives, such as a reduction in central line infection rates, an increase in hand-washing compliance, and a decrease in fall rates. In this article we will describe how our Magnet Re-Designation Accreditation Process(R) and shared governance model have contributed to strengthening our culture of patient safety. The manner in which the Magnet components of transformational leadership; structural empowerment; exemplary professional practice; new knowledge, innovation and improvement; and empirical quality results have all contributed to improved patient safety are discussed. PMID- 22324568 TI - Nurses create a culture of patient safety: it takes more than projects. AB - Healthcare organizations are embracing the sciences of safety, improvement, human factors, and complexity to transform their culture into a culture of safety and high reliability. Nurses are the front lines of healthcare delivery, and as such, the front lines of safety and quality processes and outcomes. Nurses are required to both understand and develop the skills needed to improve care processes and to own the work of improvement as a professional responsibility. These changes demand that nurses understand both the complex demands of providing harm-free care and the system dynamics needed to create the conditions for improved outcomes, organizational, and system performance, and intraprofessional development and teamwork. The author presents the challenge of maintaining a safe patient care environment and describes a model that can detect and mitigate the migration of safe nursing care into at-risk and unsafe nursing care. She emphasizes the importance of healthcare organizations performing as high reliability organizations and outlines 'planned practices' steps to introduce new technology and innovation, and concludes by considering the interaction between individual practice and system performance. PMID- 22324569 TI - Patient safety culture: the nursing unit leader's role. AB - Discussions about a culture of patient safety abound, yet nurse leaders continue to struggle to achieve such a culture in today's complex and fast-paced healthcare environment. In this article the authors discuss the concept of a patient safety culture, present a fictional scenario describing what happened in a hospital that lacked a culture of patient safety, and explain what should have happened in the above scenario. This discussion is offered within a framework consisting of seven driving factors of patient safety. These factors include leadership, evidence-based practice, teamwork, communication, and a learning, just, and patient-centered culture. Throughout, an emphasis is placed on leadership at the unit level. Nurse managers will find practical examples illustrating how leaders can help their teams establish a culture that offers the patient quality care in a safe environment. PMID- 22324570 TI - The Clinical Nurse Leader (CNL)(R): point-of-care safety clinician. AB - The vision for the Clinical Nurse Leader CNL(R) role began in 2003-2004 in response to the Institute of Medicine's quality and safety reports. The CNL was envisioned as a nurse who would provide direct clinical leadership at the point of care, working to insure that care delivery is safe, evidence-based, and targeted towards optimal quality outcomes for the cohort of clients served by the CNL. In this article the authors describe the background and intent of the CNL role and explain how the CNL is prepared to facilitate a culture of safety and to enhance safety of the care provided for a group of patients. They illustrate how the CNL enhances safety across diverse settings and conclude by noting the power that CNLs have for building continuing coalitions of safety. The value of the CNL as a front-line care leader for building and sustaining safer and higher quality care delivery environments for the future is highlighted. PMID- 22324571 TI - Teaching the culture of safety. AB - Although a healthcare culture of safety has been a practice priority for many years, there has been less attention to incorporating culture of safety content into the education of healthcare professionals. Students need to become knowledgeable about system vulnerabilities and understand how knowledge, skills, and attitudes promoting utilization of safety science will lead to safer care for patients and families. Learning about both patient safety and system vulnerabilities needs to begin in pre-licensure programs and become an integral part of learning in all phases of nursing education and practice. In this article the author will begin by reviewing the essential elements of a culture of safety and considering what students need to know about a culture of safety. She will describe activities that promote safety, high reliability organizations, and external drivers of safety, and conclude by offering strategies for integrating a culture of safety into the curriculum. PMID- 22324572 TI - Integrating YouTube into the nursing curriculum. AB - Nurse educators need to be innovative, stimulating, and engaging as they teach future nursing professionals. The use of YouTube in nursing education classes provides an easy, innovative, and user-friendly way to engage today's nursing students. YouTube presentations can be easily adapted into nursing courses at any level, be it a fundamentals course for undergraduate students or a theoretical foundations course for graduate students. In this article I will provide information to help educators effectively integrate YouTube into their course offerings. I will start by reviewing the phenomenon of social networking. Next I will discuss challenges and strategies related to YouTube learning experiences, after which I will share some of the legal considerations in using YouTube. I will conclude by describing how to engage students via YouTube and current research related to YouTube. PMID- 22324573 TI - Pursuing graduate studies in nursing education: driving and restraining forces. AB - This article articulates the growing shortage of nursing faculty and identifies factors that impact nurses' decisions to pursue graduate studies in nursing education. Kurt Lewin's Force Field Analysis and a Decision Matrix are applied to the process of pursuing graduate studies in nursing education. When driving forces outweigh restraining forces, nurses are more likely to pursue graduate studies in nursing education. Innovative solutions to strengthen driving forces and overcome restraining forces include: offering more programs with a focus in nursing education; financial support; flexible program delivery options, including more online graduate programs; mentoring; and collaborations between employers and academic institutions. The implications of this analysis for nurses, academic nurse leaders and nursing faculty, nurse employers, and governing bodies are presented. PMID- 22324574 TI - Using effects-based reasoning to examine the DNP as the single entry degree for advanced practice nursing. AB - In October 2004 the American Association of Colleges of Nursing (AACN) endorsed the Doctor of Nursing Practice (DNP) as the single entry degree for advanced practice nurses (APNs) beginning in 2015. This action initiated significant changes in many graduate nursing programs. Currently 153 DNP programs have enrolled students and an additional 106 programs are in varying stages of development. This article will examine real and potential outcomes of having the DNP degree as the single entry level for APN practice using an effects-based reasoning framework. The author begins with a discussion of factors that influenced the DNP initiative and an explanation of effects-based reasoning. Within an effects-based framework, the author examines acceptance or rejection of the DNP initiative by APN programs and professional organizations, as well as the effects within the broader healthcare community. Concluding observations will be shared. PMID- 22324575 TI - Legislative: population-based health datasets - part 1: an overview advocating evidence-based health policy. PMID- 22324576 TI - Legislative: population-based health datasets - part 2: conducting a study through the use of an interactive search feature. PMID- 22324577 TI - Hematite nanoparticles larger than 90 nm show no sign of toxicity in terms of lactate dehydrogenase release, nitric oxide generation, apoptosis, and comet assay in murine alveolar macrophages and human lung epithelial cells. AB - Three hematite samples were synthesized by precipitation from a FeCl3 solution under controlled pH and temperature conditions in different morphology and dimensions: (i) microsized (average diameter 1.2 MUm); (ii) submicrosized (250 nm); and (iii) nanosized (90 nm). To gain insight into reactions potentially occurring in vivo at the particle-lung interface following dust inhalation, several physicochemical features relevant to pathogenicity were measured (free radical generation in cell-free tests, metal release, and antioxidant depletion), and cellular toxicity assays on human lung epithelial cells (A549) and murine alveolar macrophages (MH-S) were carried out (LDH release, apoptosis detection, DNA damage, and nitric oxide synthesis). The decrease in particles size, from 1.2 MUm to 90 nm, only caused a slight increase in structural defects (disorder of the hematite phase and the presence of surface ferrous ions) without enhancing surface reactivity or cellular responses in the concentration range between 20 and 100 MUg cm-2. PMID- 22324579 TI - Impact of the 1998 football World Cup on suicide rates in France: results from the national death registry. AB - Our objective was to determine whether the Federation Internationale de Football Association (FIFA) World Cup in 1998 had a short-term impact on the number of suicides in France. Exhaustive individual daily data on suicides from 1979 to 2006 were obtained from the French epidemiological center on the medical causes of death (CepiDC-INSERM; France). These data were analyzed using the seasonal ARIMA model. The overall effect of the World Cup was tested together with potential specific impact on days following the French team games. Between 11th June and 11th July, a significant decline of 95 suicides was observed (-10.3%), this effect being the strongest among men and people aged between 30 and 44. A significant decrease was also observed for the days following French team games ( 19.9%). Our results are in favor of an effect of nationwide sport events on suicidal behaviors and are consistent with other studies. Many of the theories explaining the relationship between sports and suicide are related to sense of belongingness and social integration, highlighting the importance of social link reinforcement in suicide prevention. PMID- 22324582 TI - High-performance liquid chromatography on small particle silica gel. PMID- 22324580 TI - Editorial. Analytical Chemistry in Environmental Science. VI. The Pros and Cons of Standard Method. PMID- 22324583 TI - Influence of column configuration on performance in high efficiency liquid chromatography. PMID- 22324584 TI - Characterization of exponentially modified Gaussian peaks in chromatography. PMID- 22324585 TI - Separation and quantitative determination of the yttrium group lanthanides by gas liquid chromatography. PMID- 22324586 TI - Exact treatment of diffusion in gas chromatography. PMID- 22324587 TI - Support-bonded polyaromatic copolymer stationary phases for use in gas chromatography. PMID- 22324589 TI - Plasma chromatography of the monohalogenated benzenes. PMID- 22324588 TI - Electrochemical cell as a gas chromatograph-mass spectrometer interface. PMID- 22324590 TI - Response of a calcium-selective electrode in acid solutions. PMID- 22324591 TI - Successive photometric titration of calcium and magnesium. PMID- 22324592 TI - Sampled-data approach to the reduction of uncompensated resistance effects in potentiostatic experiments. PMID- 22324593 TI - Experimental evaluation of cyclic voltammetry theory for disproportionation reactions. PMID- 22324594 TI - Structural determination of monosubstituted alkylbenzenes by proton magnetic resonance. PMID- 22324595 TI - Rapid, phase-sensitive, three-electrode alternating current polarography. PMID- 22324596 TI - Ultrasonic nebulization in a low-emission flame for atomic fluorescence spectrometry. PMID- 22324597 TI - Colorimetric determination of calcium using reagents of the glyoxal bis(2 hydroxyanil) class. PMID- 22324598 TI - Quantitative sampling from a vertical tube reactor. PMID- 22324599 TI - Critical evaluation of the Karl Fischer water method, end-point detection system, and standardization. PMID- 22324600 TI - Isothermal decomposition of isothiocyanatopentaamine cobalt(III) perchlorate. Particle size effect. PMID- 22324601 TI - Prototype charts for identifying biaxial phases. PMID- 22324602 TI - Chelation of boric acid with nitropyrocatechols and the photometric determination of boric acids. PMID- 22324603 TI - Precision and detection limits of cadmium, manganese, cobalt, and nickel in sulfides by electron microprobe analysis. PMID- 22324604 TI - Kinetic study of the initial cyclization of methylbis(.beta.-chloroethyl)amine hydrochloride using chloride ion-selective electrodes. PMID- 22324605 TI - Detection of nanogram quantitites of hexachlorophene by ultraviolet liquid chromatography. PMID- 22324606 TI - Hamming type codes applied to learning machine determinations of molecular formulas. PMID- 22324608 TI - Estimation of trace amounts of chrysotile asbestos by x-ray diffraction. PMID- 22324607 TI - Titrimetric determination of ionic and coordinated azide ion by oxidation with excess nitrite ion in acid solution. PMID- 22324609 TI - Gravimetric analysis of uranyl orthophosphate mixtures. PMID- 22324610 TI - Acidimetric titration of heavy metal acetates. PMID- 22324611 TI - Determination of scandium by precipitation with benzilic acid. PMID- 22324612 TI - Electrolytic sample preparation and its application to atomic absorption. Rapid determination of magnesium in cast iron. PMID- 22324613 TI - Principles of hot plate chromatography. PMID- 22324615 TI - Separation of thorium from lanthanum and other elements by cation-exchange chromatography at elevated temperatures. PMID- 22324614 TI - Study of cobalt(III) complexes by atomic absorption spectrometry. Effect of ligands and distribution of atomic cobalt in the flame. PMID- 22324616 TI - Determination of lanthanum in cobalt-base alloys by x-ray fluorescence spectrometry. PMID- 22324617 TI - Determination of chromatographic resolution for peaks of vast concentration differences. PMID- 22324619 TI - "Trading rules" in infrared Fourier transform spectroscopy. PMID- 22324618 TI - Smoothing and differentiation of data by simplified least square procedure. PMID- 22324620 TI - Rapid atomic absorption determination of silver and copper by sequential atomization from a graphite rod. PMID- 22324621 TI - Molecular design. Tetrachloroterephthaloyl oligomers as liquid phases for gas chromatography. PMID- 22324623 TI - Geiger-Mueller counter designed to measure reproducibly activities retained on resin columns. PMID- 22324622 TI - Use of large overpotentials in galvanostatic measurements. PMID- 22324624 TI - Thermo-barometer. PMID- 22324626 TI - Triac switching circiutry for eliminating interfering transients in digital logic automated systems. PMID- 22324625 TI - New, simple windowless cell for front-surface fluorometry. PMID- 22324627 TI - Technique for chemical ionization operation of a CEC 21-110B mass spectrometer. PMID- 22324628 TI - Variable-ratio stopped-flow mixing device. PMID- 22324629 TI - Partial anomalous left pulmonary artery along with aortic coarctation in an infant with Kabuki syndrome. AB - We report an antenatally diagnosed fetal coarctation delivered prematurely and confirmed to have coarctation as well as additional nonobstructing anomalous left pulmonary artery branch (aLPA) from right pulmonary artery (RPA) and significant dysmorphic features. The baby underwent an uncomplicated arch repair, but had numerous multisystem and growth related issues prompting a diagnosis of Kabuki syndrome (KS) at 1 year of age. While coarctation and hypoplastic left heart syndrome are observed in this syndrome, this is the second reported case of aLPA in KS and the first with the forme fruste of left-sided obstruction as well as aLPA in this group of patients. PMID- 22324630 TI - Taiwanese translation and psychometric testing of the Revised Illness Perception Questionnaire for patients with traumatic injury. AB - AIMS: The purpose of this study was to undertake a cross-cultural adaptation, translation and psychometric analysis of the Illness Perception Questionnaire Revised for patients with traumatic injury in Taiwan. BACKGROUND: Illness representations are the cognitive understandings and emotional responses individuals develop, which help to determine their responses to health threats. METHODS: This methodological study involved four phases. First, two subscales, identity and causes were modified. Second, translation and back translation was undertaken by four translators, moderated by an expert committee. Third, ten patients with traumatic injury pilot tested the feasibility and readability of the Chinese Illness Perception Questionnaire Revised (Trauma), and three professionals assessed the scale for content validity, resulting in minor modifications. Finally, 173 patients with traumatic injury were recruited to the main study and completed the Chinese Illness Perception Questionnaire Revised (Trauma). Item analysis, factor analysis, Cronbach's alpha and split-half reliability were used to the psychometric properties of the Chinese Illness Perception Questionnaire Revised (Trauma). RESULTS: Eight items were removed from the scale as a result of the item analysis. The factor analysis demonstrated a six-factor structure explained 60.3% of the total item variance in the scale, which was very similar to the original scale. The Cronbach's alphas ranged from 0.69-0.80 for each subscale, and the split-half reliability coefficients were from 0.70-0.82. CONCLUSION: The Chinese Illness Perception Questionnaire Revised (Trauma) had good psychometric properties. RELEVANCE TO CLINICAL PRACTICE: Translation of the instrument into Chinese extends its utility to the traumatic injury population. Awareness of patients' illness representations can help clinicians provide appropriate interventions to patients. PMID- 22324631 TI - Catalytic Pt-on-Au nanostructures: why Pt becomes more active on smaller Au particles. AB - Platinum is a widely used precious metal in many catalytic nanostructures. Engineering the surface electronic structure of Pt-containing bi- or multimetallic nanostructure to enhance both the intrinsic activity and dispersion of Pt has remained a challenge. By constructing Pt-on-Au (Pt^Au) nanostructures using a series of monodisperse Au nanoparticles in the size range of 2-14 nm, we disclose herein a new approach to steadily change both properties of Pt in electrocatalysis with downsizing of the Au nanoparticles. A combined tuning of Pt dispersion and its surface electronic structure is shown as a consequence of the changes in the size and valence-band structure of Au, which leads to significantly enhanced Pt mass-activity on the small Au nanoparticles. Fully dispersed Pt entities on the smallest Au nanoparticles (2 nm) exhibit the highest mass-activity to date towards formic acid electrooxidation, being 2 orders of magnitude (75-300 folds) higher than conventional Pt/C catalyst. Fundamental relationships correlating the Pt intrinsic activity in Pt^Au nanostructures with the experimentally determined surface electronic structures (d-band center energies) of the Pt entities and their underlying Au nanoparticles are established. PMID- 22324632 TI - Spinal muscular atrophy pathogenic mutations impair the axonogenic properties of axonal-survival of motor neuron. AB - The axonal survival of motor neuron (a-SMN) protein is a truncated isoform of SMN1, the spinal muscular atrophy (SMA) disease gene. a-SMN is selectively localized in axons and endowed with remarkable axonogenic properties. At present, the role of a-SMN in SMA is unknown. As a first step to verify a link between a SMN and SMA, we investigated by means of over-expression experiments in neuroblastoma-spinal cord hybrid cell line (NSC34) whether SMA pathogenic mutations located in the N-terminal part of the protein affected a-SMN function. We demonstrated here that either SMN1 missense mutations or small intragenic re arrangements located in the Tudor domain consistently altered the a-SMN capability of inducing axonal elongation in vitro. Mutated human a-SMN proteins determined in almost all NSC34 motor neurons the growth of short axons with prominent morphologic abnormalities. Our data indicate that the Tudor domain is critical in dictating a-SMN function possibly because it is an association domain for proteins involved in axon growth. They also indicate that Tudor domain mutations are functionally relevant not only for FL-SMN but also for a-SMN, raising the possibility that also a-SMN loss of function may contribute to the pathogenic steps leading to SMA. PMID- 22324633 TI - Career choice and place of graduation among physicians in Norway. AB - OBJECTIVE: To investigate to what extent a physician's place of graduation is associated with the physician choosing a career as a general practitioner (GP), and identify factors in the curriculum that could predict a general practice career. DESIGN: Cross-sectional study based on the membership database of the Norwegian Medical Association. SETTING: Physicians working in Norway who graduated from four domestic medical schools, five other countries, and three groups of countries. Physicians were categorized according to their main professional activity as GPs, hospital physicians, and researchers. SUBJECTS: A total of 2836 medical physicians who were working in Norway during 2010 and graduated from medical school between 2002 and 2005. MAIN OUTCOME MEASURES: Percentage and odds ratio for subjects working as a GP in Norway during 2010. Descriptive data for pre-graduate general practice education in Norwegian medical schools were also analysed. RESULTS: Compared with the University of Oslo, there was a significantly higher proportion of GPs among physicians who had graduated from Denmark (OR 2.9, 95% CI 1.9-4.5), Poland (OR 2.0, 95% CI 1.4-2.9), Sweden (OR 1.8, 95% CI 1.0-3.1), and Trondheim (Norway) (OR 1.5, 95% CI 1.1-2.0). Across the four Norwegian medical schools, there were significant associations between choosing a general practice career and the sum of pre-graduate educational hours regarding general practice, general practice preceptorship, and the number of GP teachers. CONCLUSION: The physician's place of graduation appears to be associated with career choice. The universities' total contribution in pre graduate general practice education may be associated with future GP career choice. PMID- 22324634 TI - A simple and accurate method for determining wheat grain fructan content and average degree of polymerization. AB - An improved method for the measurement of fructans in wheat grains is presented. A mild acid treatment is used for fructan hydrolysis, followed by analysis of the released glucose and fructose with high performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD). Not only the amount of fructose set free from fructans but also the released glucose can be quantified accurately, allowing determination of the average degree of polymerization of fructans (DP(av)). Application of the mild acid treatment to different grain samples demonstrated that a correction should be made for the presence of sucrose and raffinose, but not for stachyose or higher raffinose oligosaccharides. The fructan content and DP(av) of spelt flour, wheat flour, and whole wheat flour were 0.6%, 1.2%, and 1.8% of the total weight and 4, 5, and 6, respectively. Validation experiments demonstrate that the proposed quantification method is accurate and repeatable and that also the DP(av) determination is precise. PMID- 22324635 TI - Channel-length-dependent transport and photovoltaic characteristics of carbon nanotube-based, barrier-free bipolar diode. AB - Carbon nanotube (CNT) diodes with different channel length between L = 0.6 MUm to 3.5 MUm are fabricated on the same tube, and the electric and photovoltaic characteristics are investigated. It is found that although the open voltage of the diode increases rapidly for channel length L less than 1.0 MUm, it saturates for longer channel devices. On the other hand, the short circuit current of the diode exhibites a clear peak at intermediate channel length of about 1.5 MUm, a large leakage current via tunneling for short channel device and significantly decreased current for long channel device due to the increased recombination and channel resistance. The optimal channel length for a CNT diode in photovoltaic application is thus determined to be about 1.5 MUm. PMID- 22324636 TI - A thiopyranchromenone and other chromone derivatives from an Endolichenic fungus, Preussia africana. AB - The first example of a naturally occurring thiopyranchromenone, preussochromone A (1), and five other new chromone derivatives, preussochromones B-F (2-6), were isolated from solid cultures of an endolichenic fungus, Preussia africana. The structures of 1-6 were established primarily by NMR experiments, and 2 and 4 were further confirmed by X-ray crystallography. The absolute configurations of 1 and 2 were determined by the application of electronic circular dichroism (ECD), whereas those of C-5 in 3, C-6 in 4, and the 6,7-diol in 5 were deduced via the CD data of the in situ formed [Rh2(OCOCF3)4] complex, the modified Mosher method, and Snatzke's method, respectively. Compounds 1 and 3 showed significant cytotoxicity against A549 cells. PMID- 22324637 TI - Speciation of arsenic, chromium, and vanadium in red mud samples from the Ajka spill site, Hungary. AB - Results are presented from X-ray absorption spectroscopy based analysis of As, Cr, and V speciation within samples of bauxite ore processing residue (red mud) collected from the spill site at Ajka, Western Hungary. Cr K-edge XANES analysis found that Cr is present as Cr(3+) substituted into hematite, consistent with TEM analysis. V K-edge XANES spectra have E(1/2) position and pre-edge features consistent with the presence of V(5+) species, possibly associated with Ca aluminosilicate phases. As K-edge XANES spectra identified As present as As(5+). EXAFS analysis reveals arsenate phases in red mud samples. When alkaline leachate from the spill site is neutralized with HCl, 94% As and 71% V are removed from solution during the formation of amorphous Al-oxyhydroxide. EXAFS analysis of As in this precipitate reveals the presence of arsenate Al-oxyhydroxide surface complexes. These results suggest that in the circumneutral pH, oxic conditions found in the Torna and Upper Marcal catchments, incorporation and sorption, respectively, will restrict the environmental mobility of Cr and As. V is inefficiently removed from solution by neutralization, therefore, the red mud may act as a source of mobile V(5+) where the red mud deposits are not removed from affected land. PMID- 22324638 TI - Clinical and dermoscopic features of small Reed nevus (<6 mm). AB - BACKGROUND: The differential diagnosis between Reed nevi and melanoma becomes more difficult if the lesion to analyse presents a small size, with a diameter of 6 mm or smaller. Many studies have reported various dermoscopic features of Reed nevi during their growth phases. In early stages of evolution, the lesions generally show a characteristic globular appearance typically found in childhood, followed by the so-called starburst pattern. OBJECTIVE: The aim of the study was to identify the main dermoscopic features in small Reed nevi (<6 mm in size). METHODS: Using a computerized skin-imaging database for melanoma prevention surgery at the Department of Dermatology of the University of Florence, 15 Reed nevi were selected among 103 small (<6 mm) melanocytic lesions consecutively excised. Images of small Reed nevi, independently blinded to histopathological diagnosis, were administered to a dermatologist expert in dermoscopy, who separately examined the clinical and the dermatoscopic images of small Reed nevi and evaluated their clinical and dermoscopic parameters. RESULTS: Analysis of the main dermoscopic patterns showed that 40% had a reticular pattern, 20% had a starburst pattern, 6.5% had a globular pattern, 6.5% had a homogeneous pattern and 27% had an atypical pattern. CONCLUSION: We propose that small, early-stage Reed nevus are not characterized by an evolution of growth patterns to a phenotype typical of larger lesions. We assume that the patterns are distributed in a linear manner between age groups, may all be present at the outset and thus are independent from the various stages of nevus development. PMID- 22324640 TI - Outcomes and process in the care of the disabled child. PMID- 22324639 TI - Kinetic analysis of the bypass of a bulky DNA lesion catalyzed by human Y-family DNA polymerases. AB - 1-Nitropyrene (1-NP), a mutagen and potential carcinogen, is the most abundant nitro polyaromatic hydrocarbon in diesel exhaust, which reacts with DNA to form predominantly N-(deoxyguanosin-8-yl)-1-aminopyrene (dG(AP)). If not repaired, this DNA lesion is presumably bypassed in vivo by any of human Y-family DNA polymerases kappa (hPolkappa), iota (hPoliota), eta (hPoleta), and Rev1 (hRev1). Our running start assays demonstrated that each of these enzymes was indeed capable of traversing a site-specifically placed dG(AP) on a synthetic DNA template but that hRev1 was stopped after lesion bypass. The time required to bypass 50% of the dG(AP) sites (t(50)(bypass)) encountered by hPoleta, hPolkappa, and hPoliota was determined to be 2.5 s, 4.1 s, and 106.5 s, respectively. The efficiency order of catalyzing translesion synthesis of dG(AP) (hPoleta > hPolkappa > hPoliota ? hRev1) is the same as the order for these human Y-family enzymes to elongate undamaged DNA. Although hPoleta bypassed dG(AP) efficiently, replication by both hPolkappa and hPoliota was strongly stalled at the lesion site and at a site immediately downstream from dG(AP). By employing presteady state kinetic methods, a kinetic basis was established for polymerase pausing at these DNA template sites. Besides efficiency of bypass, the fidelity of those low fidelity polymerases at these pause sites was also significantly decreased. Thus, if the translesion DNA synthesis of dG(AP)in vivo is catalyzed by a human Y family DNA polymerase, e.g., hPoleta, the process is certainly mutagenic. PMID- 22324641 TI - Ethical perspectives in cooling for term infants with intrapartum asphyxia. PMID- 22324642 TI - A neural systems approach in autism spectrum disorders. PMID- 22324643 TI - Cloperastine-based cough syrup and acute dystonic reactions. PMID- 22324644 TI - Training traditional birth attendants on the WHO Essential Newborn Care reduces perinatal mortality. AB - OBJECTIVES: To evaluate the impact of birth attendant training using the World Health Organization Essential Newborn Care (ENC) course among traditional birth attendants, with a particular emphasis on the effect of acquisition of skills on perinatal outcomes. DESIGN: Population-based, prospective, interventional pre post design study. SETTING: 11 rural clusters in Chimaltenango, Guatemala. POPULATION: Health care providers. METHODS: This study analyzed the effect of training and implementation of the ENC health care provider training course between September 2005 and December 2006. OUTCOME MEASURES: The primary outcome measure was the rate of death from all causes in the first seven days after birth in fetuses/infants >=1500g. Secondary outcome measures were overall rate of stillbirth, rate of perinatal death, which included stillbirths plus neonatal deaths in the first seven days in fetuses/infants >=1500g. RESULTS: Perinatal mortality decreased from 39.5/1000 pre-ENC to 26.4 post-ENC (RR 0.72; 95%CI 0.54 0.97). This reduction was attributable almost entirely to a decrease in the stillbirth rate of 21.4/1000 pre-Essential Newborn Care to 7.9/1000 post-ENC (RR 0.40; 95%CI 0.25-0.64). Seven-day neonatal mortality did not decrease (18.3/1000 to 18.6/1000; RR 1.05; 95%CI 0.70-1.57). CONCLUSION: Essential Newborn Care training reduced stillbirths in a population-based controlled study with deliveries conducted almost exclusively by traditional birth attendants. Scale-up of this intervention in other settings might help assess reproducibility and sustainability. PMID- 22324645 TI - Persistence with oral contraceptive pills versus metformin in women with polycystic ovary syndrome. AB - OBJECTIVE: We studied patient persistence with oral contraceptive pills (OCPs) compared to metformin for treatment of polycystic ovary syndrome (PCOS) in an urban university clinic population. METHODS: We conducted a retrospective cohort study of women with PCOS who were treated in our specialty clinic between 2004 and 2006. All women with the diagnosis of PCOS, defined as oligomenorrhea or amenorrhea in conjunction with clinical or biochemical evidence of hyperandrogenism, with exclusion of other causes, were included in the study. We abstracted data on demographic characteristics, medical history, anthropometrical measures, desire for pregnancy, prescribed treatment, and patient report of persistence with treatment at 3, 6, and 12 months. The primary outcome measure was persistence with prescribed treatment. RESULTS: One hundred nineteen subjects were included in the study. Demographic and anthropometrical characteristics were similar between the groups. At 3 months, 57.1% were persistent with OCPs, and 57.8% were persistent with metformin (p=0.93). At 6 months, the percentages dropped to 38.1% with OCPs and 43.9% with metformin (p=0.46). At 12 months, only 21.7% continued with OCPs compared to 31.2% with metformin (p=0.19). Subjects were significantly more likely to be persistent with either OCPs or metformin at 3 months compared to either 6 or 12 months (p<0.01). CONCLUSIONS: Women with PCOS showed similar persistence rates with OCPs compared to metformin. Persistence with either treatment precipitously decreases over time and is modest at 12 months. PMID- 22324646 TI - You can't fool mother nature: new directions in oral contraception. PMID- 22324647 TI - Do people who "mature out" of drinking see themselves as more mature? AB - BACKGROUND: Self-perceptions of adulthood during the 20s and 30s are influenced by role transitions, age-related norms, and character traits. These factors are also associated with alcohol use disorders (AUDs), which peak and subsequently decrease during this time of life. Previous developmental research has found that alcohol misuse in adolescence predicts lower reported maturity, whereas alcohol misuse in emerging adulthood is not related to maturity. This study examines how self-perceived maturity (SPM) is affected by AUD status, maturity-related personality characteristics, and role transition variables at ages 25, 29, and 35, and how those relationships change over time. METHODS: Data were drawn from a cohort study of 410 college students (N = 489 at baseline). Students were ascertained as first-time freshmen at a large, public midwestern university in the fall of 1987 but were followed up regardless of subsequent enrollment. The data for the current study were drawn from Waves 5 to 7, when participants were, on average, 25, 29, and 35 years of age. Structural equation modeling was used to determine whether the relation between the SPM item "I feel mature for my age" and DSM-III AUD status was moderated by age. RESULTS: Results suggested that individuals with AUDs are more likely to endorse lower SPM levels compared to their nondiagnosing peers at ages 29 and 35 but not at age 25. In contrast, none of the relations between Conscientiousness, concern about Future Consequences, role status variables, and AUD was moderated by time. CONCLUSIONS: These results suggest that alcohol-related problems may be perceived as more "age appropriate" during the mid-20s than at later ages in life and that such developmentally sensitive aspects of self-concept might be useful in cognitive interventions for young adults. PMID- 22324648 TI - Acute kidney injury following coronary artery bypass grafting: early mortality and postoperative complications. AB - OBJECTIVES: To investigate the prognostic importance of acute kidney injury on early mortality, postoperative stroke, and mediastinitis in patients undergoing a first isolated coronary artery bypass grafting. DESIGN: 7594 patients undergoing coronary artery bypass grafting with information on pre- and postoperative serum creatinine values were included. Patients were classified using the Acute Kidney Injury Network classification. Odds ratios (OR) for mortality and postoperative complications within 60 days of surgery were calculated after adjustment for confounders separately for stage 1 and for stages 2 and 3 together. RESULTS: 1047 (14%) patients developed acute kidney injury. There were 132 (1.7%) deaths, 103 (1.4%) strokes and 118 (1.6%) cases of mediastinitis during follow-up. Among patients in stage 1 the adjusted odds ratio for death was 4.36 (95% confidence interval 2.83-6.71) and for stage 2 plus 3; 21.5 (12.0-38.6) compared to patients without acute kidney injury. Corresponding OR for stroke were 2.34 (1.43-3.82) and 6.52 (2.97-14.3) and for mediastinitis 2.88 (1.84-4.50) and 4.68 (2.07-10.6), respectively. CONCLUSIONS: Acute kidney injury following coronary artery bypass grafting is related to postoperative mortality, stroke, and mediastinitis. Patients undergoing coronary artery bypass grafting should be assessed for presence of acute kidney injury postoperatively, in order to predict early prognosis. PMID- 22324649 TI - Concern about HIV and AIDS among older people in the slums of Nairobi, Kenya. AB - The article explores the way that social networks and personal experiences affect perceived HIV-related concerns among people aged 50 years or older living in a low resource neighborhood with high HIV prevalence in Nairobi, Kenya. Multiple logistic regression is used to model the association between the reporting of an HIV-related concern and individual-level characteristics, personal experiences, and social interaction. The main concerns regarding HIV reported by older people in the study included caring for orphaned children (65%), caring for people with AIDS (48%), and losing material and social support from adult children (36%). Interestingly, 38% of respondents voiced concerns about HIV infection among older people. Respondents who had been individually affected by HIV and AIDS, who were part of a wide social network, or who participated in community activities were frequently more likely to report a concern. The findings highlight the significance of the role of social interaction and social networks in the diffusion of information and knowledge. These findings have implications for HIV and AIDS policy and programs, highlighting the potential for social networks and community-level interventions to educate and increase awareness about HIV and AIDS among older people. Community leaders can make good peer educators and communication agents for HIV/AIDS campaigns. Additionally, the recognized high level of personal vulnerability to HIV infection among older people suggests the need for targeted sexual behavior change programs among this often neglected group. PMID- 22324650 TI - Increase in flavan-3-ols by silencing flavonol synthase mRNA affects the transcript expression and activity levels of antioxidant enzymes in tobacco. AB - Flavonoids are plant secondary metabolites widespread throughout the plant kingdom involved in many physiological and biochemical functions. Amongst the flavonoids, flavan-3-ols (catechin and epicatechin) are known for their direct free radical scavenging activity in vitro, but studies on their antioxidant potential and interaction with antioxidant enzymes in vivo are lacking. Here, the flavonoid pathway was engineered by silencing a gene encoding flavonol synthase (FLS) in tobacco to direct the flow of metabolites towards production of flavan-3 ols. FLS silencing reduced flavonol content 17-53%, while it increased catechin and epicatechin content 51-93% and 18-27%, respectively. The silenced lines showed a significant increase in expression of genes for dihydroflavonol reductase and anthocyanidin synthase, a downstream gene towards epicatechin production, with no significant change in expression of other genes of the flavonoid pathway. Effects of accumulation of flavan-3-ols in FLS silenced lines on transcript level and activities of antioxidant enzymes were studied. Transcripts of the antioxidant enzymes glutathione reductase (GR), ascorbate peroxidase (APx), and catalase (CAT) increased, while glutathione-S-transferase (GST), decreased in FLS silenced lines. Enhanced activity of all the antioxidant enzymes was observed in silenced tobacco lines. To validate the affect of flavan 3-ols on the antioxidant system, in vitro experiments were conducted with tobacco seedlings exposed to two concentrations of catechin (10 and 50 MUm) for 2 days. In vitro exposed seedlings produced similar levels of transcripts and activity of antioxidant enzymes as FLS silenced seedlings. Results suggest that flavan-3-ols (catechin) might be increasing activity of GR, Apx and CAT by elevating their mRNAs levels. Since these enzymes are involved in scavenging of reactive oxygen species, this strategy would help in tailoring crops for enhanced catechin production as well as making them tolerant to oxidative stresses. PMID- 22324652 TI - Laser-heating-induced displacement of surfactants on the water surface. AB - We report a combined vibrational sum-frequency generation (SFG) spectroscopy, Brewster angle microscopy (BAM), and ellipsometry study of different surfactants on water as a function of surfactant density. Vibrational SFG spectra of surfactants on the water surface in a Langmuir trough have been measured in both the surfactant CH and the water OH stretch regions. At low densities, the SFG signal generated at the surface in the presence of the surfactant is indistinguishable from the SFG signal generated at the clean water-air interface. When the surfactant density increases, i.e., upon compressing the monolayer, a very sudden increase in the SFG signal in both the CH and OH spectral regions is observed. For higher laser fluences, this stepwise increase occurs at increasingly higher surfactant densities. Since BAM shows that surfactant molecules are clearly present at these low densities, we conclude that at low surfactant density the laser beam displaces relatively high-density domains with surfactants in the liquid expanded phase out of the region of the laser focus. This is a consequence of the thermal gradient induced by local heating of the water phase with the monolayer on top due to repetitive laser excitation at 1 kHz. It can be circumvented by using a rotating trough. In this manner, the sampled surface area can be refreshed, allowing artifact-free vibrational SFG spectra to be measured down to the very lowest surfactant densities. In ellipsometry experiments, a similar step can be noticed, which, however, is of a different nature; i.e., it is not related to heating (the laser fluence is very low and the light nonresonant) but to a molecular transition. The occurrence of the step in ellipsometry as a function of area per molecule depends critically on the preparation of the monolayer. By giving the molecules time and space to relax during the preparation of the monolayer, this step could also be eliminated. PMID- 22324653 TI - Dielectric studies on the heterogeneity and interfacial property of composites made of polyacene quinone radical polymers and sulfonated polyurethanes. AB - Sulfonated polyurethane (PUI, matrix) is synthesized and composited with polyacene quinone radical polymers (PAQRs, filler). The polarization mechanism of these polymers and composites were investigated in terms of their frequency, temperature, and filler-concentration-dependent dielectric properties. We found that PUI/PAQR composites have a high permittivity, which is attributed to the filler-matrix interfacial polarization and the contact effect. The PAQR concentration-dependent permittivity of different PUI/PAQR composites reveals a percolation threshold at 20-30 wt % with scaling exponents that indicate the intercluster polarization. The frequency dependence of dielectric response is well-fitted by using the Debye and Cole-Cole functions on the basis of the structural diagrams and equivalent circuit, leading to a detailed evaluation on heterogeneous structures of different PUI/PAQR composites. PMID- 22324654 TI - Enhanced life-role participation in response to comprehensive gait training in chronic-stroke survivors. AB - PURPOSE: Intensive gait training can produce improvements in gait and function (> 6 months after stroke); however, findings are mixed for enhanced life-role participation. Therefore, it is unclear if improved gait and function translate into life-role participation gain. Our objective was to evaluate whether intensive gait therapy can produce improvements in life-role participation for chronic-stroke survivors, according to a comprehensive measure dedicated to life role participation. METHODS: In conjunction with a clinical gait-training trial, we conducted a secondary analysis for a 44-member cohort with stroke (> 6 months). Gait-training interventions included functional neuromuscular stimulation, body-weight supported treadmill training, over-ground gait training and exercise for 1.5 hours/day, 4 days/week for 12 weeks. Study measures included Tinetti Gait (gait impairment), Functional Independence Measure (FIM, function), Stroke Impact Scale subscale of life-role participation (SIS part) and Craig Handicap Assessment and Reporting Technique (CHART, life-role participation). Analysis included Wilcoxon signed rank test and polytomous universal regression model. RESULTS: Gait interventions produced significant improvement in CHART (p = 0.020), SIS part (p = 0.011), FIM (p < 0.0001), and Tinetti Gait (p < 0.0001). Age, gender and time since stroke did not predict response to treatment. CONCLUSIONS: Intensive gait therapy resulted in significant gain in life-role participation, according to a comprehensive measure, so dedicated. PMID- 22324655 TI - The Norwegian version of the PTSD Checklist (PCL): construct validity in a community sample of 2004 tsunami survivors. AB - BACKGROUND: The PTSD Checklist (PCL) is a widely used self-administered measure of post-traumatic stress disorder (PTSD) and it has been validated in a variety of languages and cultures. AIM: Evaluate the diagnostic validity of the Norwegian version of a specific PCL (PCL-S) for detecting PTSD in epidemiological research. METHODS: Participants were severely exposed Norwegian survivors from the 2004 South-East Asian tsunami. Of 75 individuals asked to participate, 63 responded (84%). PTSD was assessed by PCL-S and the Structured Clinical Interview for DSM IV Axis I Disorders (SCID-I). These instruments were compared to evaluate the diagnostic validity of the PCL. We used two different scoring methods to diagnose PTSD based on PCL. The first method was based on the dichotomized sum score (cut off >= 50) and the second was based on the flowchart method following DSM-IV symptom criteria. Area under the curve (AUC), Cohen's kappa, sensitivity and specificity were used to evaluate the agreement between the PCL and SCID-I. RESULTS: According to the clinical interview, 11.3% of the participants met the diagnostic criteria for PTSD. The two scoring methods of PCL-S revealed similar results: according to both methods, 14.5% were categorized with PTSD. AUC was 0.98 (95% CI 0.93-1.00). For Cohen's kappa, the agreement was 0.71. Sensitivity was 0.86 and specificity 0.95. Agreement between PCL and SCID-I investigated for each of the three symptom clusters of PTSD and for the 17 individual items showed mostly a moderate to substantial agreement. CONCLUSIONS: The Norwegian version of the PCL-S performed well as a diagnostic instrument for detecting PTSD in epidemiological research. PMID- 22324656 TI - Young people's overestimation of peer substance use: an exaggerated phenomenon? AB - AIMS: This paper queries the notion that young people overestimate peer substance use, asking whether there is robust evidence that such misperceptions are widespread and whether the phenomenon may have been exaggerated in the research literature. METHOD: An examination of the research literature was conducted, focusing mainly on studies published since 2000. Some analyses of relevant data on cannabis use from a Norwegian youth survey were also undertaken. RESULTS: The research in question is characterized by many weaknesses, including low response rates and widespread use of convenience samples, as well as the presence of contextual factors and the use of assessment tools that may have created a bias in favour of 'demonstrating' that youth overestimate peer drinking or drug use. Moreover, in some cases, the apparent tendency to hold such misbeliefs may reflect the reality. Further, although most studies conclude that the modal tendency is to overestimate, high levels of underestimation of peer substance use have been reported. There is also suggestive evidence that many youth may have no pre-existing beliefs when responding to items on the issue. Results from the Norwegian youth survey added to this picture. CONCLUSION: Young people's tendency to overestimate peer drinking and drug use has been exaggerated, while the uncertainty surrounding the evidence in question has been understated. PMID- 22324657 TI - Abrupt and dynamic changes in gene expression revealed by live cell arrays. AB - A description of the noise associated with gene expression is presented, based on a simplified form of the combined multistep processes of transcription and translation. These processes are influenced by numerous factors, including the accessibility of promoter regions to the transcriptional machinery, the kinetics of assembly of the transcription complexes, and the synthesis and degradation of both mRNA and proteins, among others. Ultimately, stochasticity in cellular processes results in variation in protein levels. Here we constructed a rationally designed RNA-based transcriptional activator to reduce these variables and provide a cleaner, more detailed portrayal of cellular noise. Functioning at a level comparable to natural transcription activation, this activator is isolated to a lacZ reporter gene in yeast cells to quantitatively describe the efficiency of the combined processes of transcription and translation. By employing single-cell array techniques to monitor individual cells simultaneously and in real time, a statistical approach to investigate noise inherent in gene expression is possible. Live cell arrays enabled cell populations to be characterized temporally at the individual cell level. The array platform allowed for a relative measure of protein production in real time and could characterize protein bursts with variable size and random timing, such that bursts occurred in a temporally indiscriminate fashion. The inherent variability and randomness of these processes is characterized, with almost half (47%) of cells experiencing bursting behavior at least once over the course of the experiment. We demonstrate that cells identified on the upper periphery of activity exhibit behaviors that are substantially different from the majority of the population, and such variable activities within a population will provide a more accurate characterization of the population. PMID- 22324658 TI - Expression and function of macrophage migration inhibitory factor in the pathogenesis of UV-induced cutaneous nonmelanoma skin cancer. AB - Chronic skin exposure to ultraviolet light stimulates the production of cytokines known to be involved in the initiation of skin cancer. Recent studies in mouse models suggested a role for macrophage migration inhibitory factor (MIF) in the UVB-induced pathogenesis of nonmelanoma skin cancer (NMSC). Our studies aimed at defining the pathophysiological function of MIF in cutaneous inflammatory reactions and in the development and progression of NMSC. Immunohistochemical analysis revealed a moderate expression of MIF in normal human skin samples but an enhanced expression of this cytokine in lesional skin of patients with actinic keratosis or cutaneous SCC. Enzyme-linked immunosorbent assay studies showed a time-dependent increase in MIF secretion after a moderate single-dose UVB irradiation in NHEKs and SCC tumor cells. MIF is known to interact with CXCR2, CXCR4 and CD74. These receptors are not constitutively expressed in keratinocytes and HaCaT cells and their expression is not induced by UVB irradiation either. However, stimulation with IFNgamma upregulated CD74 surface expression in these cells. Affymetrix((r)) Gene Chip analysis revealed that only keratinocytes prestimulated with IFNgamma are responsive to MIF. These findings indicate that MIF may be an important factor in the pathogenesis of NMSC tumorigenesis and progression in an inflammatory environment. PMID- 22324659 TI - Delineation of anatomy of the ruptured sinus of Valsalva with three-dimensional echocardiography: the advantage of the added dimension. AB - The rupture of sinus of Valsalva is a rare complication of infective endocarditis. Three-dimensional (3D) echocardiography represents an important adjunctive tool to demonstrate the ruptured sinus of Valsalva with better delineation of its characteristics. We present an adult patient with rupture of right sinus of Valsalva aneurysm due to infective endocarditis of the aortic valve, in whom the two-dimensional (2D) transthoracic echocardiogram erroneously localized the site of rupture into the right atrium. Whereas, 3D transthoracic echocardiogram accurately delineated the site of rupture into the right ventricle and it was confirmed on subsequent cardiac catheterization and angiogram. In addition, 3D echocardiography clearly showed the size and shape of the defect, which helped in successful transcatheter closure of the defect with amplatzer duct occluder device. PMID- 22324660 TI - Harmonic nanocrystals for biolabeling: a survey of optical properties and biocompatibility. AB - Nonlinear optical nanocrystals have been recently introduced as a promising alternative to fluorescent probes for multiphoton microscopy. We present for the first time a complete survey of the properties of five nanomaterials (KNbO(3), LiNbO(3), BaTiO(3), KTP, and ZnO), describing their preparation and stabilization and providing quantitative estimations of their nonlinear optical response. In the light of their prospective use as biological and clinical markers, we assess their biocompatibility on human healthy and cancerous cell lines. Finally, we demonstrate the great potential for cell imaging of these inherently nonlinear probes in terms of optical contrast, wavelength flexibility, and signal photostability. PMID- 22324661 TI - Colorimetric and fluorescent signaling of Au3+ by desulfurization of thiocoumarin. AB - We investigated the chemosignaling of Au(3+) by the selective desulfurization of thiocoumarin. In the presence of a heavy metal ion chelator N,N,N',N'-tetrakis-(2 pyridylmethyl)ethylenediamine, thiocoumarin was selectively converted to its oxo analogue by reaction with Au(3+), resulting in a pronounced chromogenic and fluorescent signaling. Selective signaling of Au(3+) was possible in the presence of common alkali, alkaline earth, and transition metal ions, as well as Au(+) in a mixed aqueous environment. The colorimetric determination of Au(3+) was possible by the color change from pink to yellowish green of the designed probe. The detection limit for the determination of Au(3+) in 50% aqueous acetonitrile was 1.1 * 10(-7) M. PMID- 22324662 TI - Gaussification and entanglement distillation of continuous-variable systems: a unifying picture. AB - Distillation of entanglement using only Gaussian operations is an important primitive in quantum communication, quantum repeater architectures, and distributed quantum computing. Existing distillation protocols for continuous degrees of freedom are only known to converge to a Gaussian state when measurements yield precisely the vacuum outcome. In sharp contrast, non-Gaussian states can be deterministically converted into Gaussian states while preserving their second moments, albeit by usually reducing their degree of entanglement. In this work-based on a novel instance of a noncommutative central limit theorem-we introduce a picture general enough to encompass the known protocols leading to Gaussian states, and new classes of protocols including multipartite distillation. This gives the experimental option of balancing the merits of success probability against entanglement produced. PMID- 22324663 TI - Entanglement of three-qubit Greenberger-Horne-Zeilinger-symmetric states. AB - The first characterization of mixed-state entanglement was achieved for two-qubit states in Werner's seminal work [Phys. Rev. A 40, 4277 (1989)]. A physically important extension concerns mixtures of a pure entangled state [such as the Greenberger-Horne-Zeilinger (GHZ) state] and the unpolarized state. These mixed states serve as benchmark for the robustness of multipartite entanglement. They share the symmetries of the GHZ state. We call such states GHZ symmetric. Here we give a complete description of the entanglement in the family of three-qubit GHZ symmetric states and, in particular, of the three-qubit generalized Werner states. Our method relies on the appropriate parametrization of the states and on the invariance of entanglement properties under general local operations. An application is the definition of a symmetrization witness for the entanglement class of arbitrary three-qubit states. PMID- 22324664 TI - Entropy production in nonequilibrium systems at stationary states. AB - We present a stochastic approach to nonequilibrium thermodynamics based on the expression of the entropy production rate advanced by Schnakenberg for systems described by a master equation. From the microscopic Schnakenberg expression we get the macroscopic bilinear form for the entropy production rate in terms of fluxes and forces. This is performed by placing the system in contact with two reservoirs with distinct sets of thermodynamic fields and by assuming an appropriate form for the transition rate. The approach is applied to an interacting lattice gas model in contact with two heat and particle reservoirs. On a square lattice, a continuous symmetry breaking phase transition takes place such that at the nonequilibrium ordered phase a heat flow sets in even when the temperatures of the reservoirs are the same. The entropy production rate is found to have a singularity at the critical point of the linear-logarithm type. PMID- 22324665 TI - Decoherence-assisted transport in a dimer system. AB - The dynamics of a dimer coupled to two different environments, each in a spin star configuration under the influence of decoherence, is studied. The exact analytical expression for the transition probability in the dimer system is obtained for different situations, i.e., independent and correlated environments. In all cases considered, it is shown that there exist well-defined ranges of parameters for which decoherent interaction with the environment assists energy transfer in the dimer system. In particular, we find that correlated environments can assist energy transfer more efficiently than separate baths. PMID- 22324666 TI - Vibrational mechanics in an optical lattice: controlling transport via potential renormalization. AB - We demonstrate theoretically and experimentally the phenomenon of vibrational resonance in a periodic potential, using cold atoms in an optical lattice as a model system. A high-frequency (HF) drive, with a frequency much larger than any characteristic frequency of the system, is applied by phase modulating one of the lattice beams. We show that the HF drive leads to the renormalization of the potential. We used transport measurements as a probe of the potential renormalization. The very same experiments also demonstrate that transport can be controlled by the HF drive via potential renormalization. PMID- 22324667 TI - Entropic splitter for particle separation. AB - We present a particle separation mechanism which induces the motion of particles of different sizes in opposite directions. The mechanism is based on the combined action of a driving force and an entropic rectification of the Brownian fluctuations caused by the asymmetric form of the channel along which particles proceed. The entropic splitting effect shown could be controlled upon variation of the geometrical parameters of the channel and could be implemented in narrow channels and microfluidic devices. PMID- 22324668 TI - Quantum gravitational contributions to the cosmic microwave background anisotropy spectrum. AB - We derive the primordial power spectrum of density fluctuations in the framework of quantum cosmology. For this purpose we perform a Born-Oppenheimer approximation to the Wheeler-DeWitt equation for an inflationary universe with a scalar field. In this way, we first recover the scale-invariant power spectrum that is found as an approximation in the simplest inflationary models. We then obtain quantum gravitational corrections to this spectrum and discuss whether they lead to measurable signatures in the cosmic microwave background anisotropy spectrum. The nonobservation so far of such corrections translates into an upper bound on the energy scale of inflation. PMID- 22324669 TI - Violation of the holographic viscosity bound in a strongly coupled anisotropic plasma. AB - We study the conductivity and shear viscosity tensors of a strongly coupled N=4 super-Yang-Mills plasma which is kept anisotropic by a theta parameter that depends linearly on one of the spatial dimensions. Its holographic dual is given by an anisotropic axion-dilaton-gravity background and has recently been proposed by Mateos and Trancanelli as a model for the preequilibrium stage of quark-gluon plasma in heavy-ion collisions. By applying the membrane paradigm which we also check by numerical evaluation of Kubo formula and lowest lying quasinormal modes, we find that the shear viscosity purely transverse to the direction of anisotropy saturates the holographic viscosity bound, whereas longitudinal shear viscosities are smaller, providing the first such example not involving higher-derivative theories of gravity and, more importantly, with fully known gauge-gravity correspondence. PMID- 22324671 TI - Upper bounds on superpartner masses from upper bounds on the Higgs boson mass. AB - The LHC is putting bounds on the Higgs boson mass. In this Letter we use those bounds to constrain the minimal supersymmetric standard model (MSSM) parameter space using the fact that, in supersymmetry, the Higgs mass is a function of the masses of sparticles, and therefore an upper bound on the Higgs mass translates into an upper bound for the masses for superpartners. We show that, although current bounds do not constrain the MSSM parameter space from above, once the Higgs mass bound improves big regions of this parameter space will be excluded, putting upper bounds on supersymmetry (SUSY) masses. On the other hand, for the case of split-SUSY we show that, for moderate or large tanbeta, the present bounds on the Higgs mass imply that the common mass for scalars cannot be greater than 10(11) GeV. We show how these bounds will evolve as LHC continues to improve the limits on the Higgs mass. PMID- 22324672 TI - Eigenvalue density of the non-Hermitian Wilson Dirac operator. AB - We find the lattice spacing dependence of the eigenvalue density of the non Hermitian Wilson Dirac operator in the epsilon domain. The starting point is the joint probability density of the corresponding random matrix theory. In addition to the density of the complex eigenvalues we also obtain the density of the real eigenvalues separately for positive and negative chiralities as well as an explicit analytical expression for the number of additional real modes. PMID- 22324673 TI - Jet flavor tomography of quark gluon plasmas at RHIC and LHC. AB - A new Monte Carlo model of jet quenching in nuclear collisions, CUJET1.0, is applied to predict the jet flavor dependence of the nuclear modification factor for fragments f=pi,D,B,e(-) from quenched jet flavors g,u,c,b in central collisions at RHIC and LHC. The nuclear modification factors for different flavors are predicted to exhibit a novel level crossing pattern over a transverse momentum range 5H(++)H(--) decaying through H(+/-+/-)->tau(+/-)tau(+/-),MU(+/ )tau(+/-),MU(+/-)MU(+/-). The search is performed in pp- collisions at a center of-mass energy of ?s = 1.96 TeV using an integrated luminosity of up to 7.0 fb( 1) collected by the D0 experiment at the Fermilab Tevatron Collider. The results are used to set 95% C.L. limits on the pair production cross section of doubly charged Higgs bosons and on their mass for different H(+/-+/-) branching fractions. Models predicting different H(+/-+/-) decays are investigated. Assuming B(H(+/-+/-)->tau(+/-)tau(+/-))=1 yields an observed (expected) lower limit on the mass of a left-handed H(L)(+/-+/-) boson of 128 (116) GeV and assuming B(H(+/-+/-)->MU(+/-)tau(+/-))=1 the corresponding limits are 144 (149) GeV. In a model with B(H(+/-+/-)->tau(+/-)tau(+/-))=B(H(+/-+/-)->MU(+/-)tau(+/ ))=B(H(+/-+/-)->MU(+/-)MU(+/-))=1/3, we obtain M(H(L)(+/-+/-))>130 (138) GeV. PMID- 22324678 TI - Electronically excited cold ion crystals. AB - The laser excitation of an ion crystal to high-lying and long-lived electronic states is a genuine many-body process even if in fact only a single ion is excited. This is a direct manifestation of the strong coupling between internal and external dynamics and becomes most apparent in the vicinity of a structural phase transition. Here we show that utilizing highly excited states offers a new approach to the coherent manipulation of ion crystals. This opens up a new route towards the creation of nonclassical motional states in a Paul trap and permits the study of quantum phenomena that rely on a strong coupling between electronic and vibrational dynamics. PMID- 22324679 TI - Observation of interference between two distinct autoionizing states in dissociative photoionization of H2. AB - Dissociative photoionization (DPI) of randomly oriented H(2) molecules has been studied using linearly polarized synchrotron radiation at selected photon energies of 31, 33, and 35 eV. Large amplitude oscillations in the photoelectron asymmetry parameter beta, as a function of electron energy, have been observed. The phase of these beta oscillations are in excellent agreement with the results of recent close coupling calculations [Fernandez and Martin, New J. Phys. 11, 043020 (2009)]. We show that the oscillations are the signature of interferences between the 1Q(1) (1)Sigma(u)(+) and 1Q(2) (1)Pi(u) doubly excited states decaying at different internuclear distances. The oscillations thus provide information about the classical paths followed by the nuclei. The presence of such oscillations is predicted to be a general phenomenon in DPI. PMID- 22324680 TI - Observation of a resonant four-body interaction in cold cesium Rydberg atoms. AB - Cold Rydberg atoms subject to long-range dipole-dipole interactions represent a particularly interesting system for exploring few-body interactions and probing the transition from 2-body physics to the many-body regime. In this work we report the direct observation of a resonant 4-body Rydberg interaction. We exploit the occurrence of an accidental quasicoincidence of a 2-body and a 4-body resonant Stark-tuned Forster process in cesium to observe a resonant energy transfer requiring the simultaneous interaction of at least four neighboring atoms. These results are relevant for the implementation of quantum gates with Rydberg atoms and for further studies of many-body physics. PMID- 22324681 TI - Subfemtosecond K-shell excitation with a few-cycle infrared laser field. AB - Subfemtosecond bursts of extreme ultraviolet radiation, facilitated by a process known as high-order harmonic generation, are a key ingredient for attosecond metrology, providing a tool to precisely initiate and probe ultrafast dynamics in the microcosms of atoms, molecules, and solids. These ultrashort pulses are always, and as a by-product of the way they are generated, accompanied by laser induced recollisions of electrons with their parent ions. By using a few-cycle infrared (lambda(0)=2.1 MUm) driving laser, we were able to directly excite high energy (~870 eV) inner-shell electrons through laser-induced electron recollision, opening the door to time-resolved studies of core-level and concomitant multielectron dynamics. PMID- 22324682 TI - Dissociative recombination of highly symmetric polyatomic ions. AB - A general first-principles theory of dissociative recombination is developed for highly symmetric molecular ions and applied to H(3)O(+) and CH(3)(+), which play an important role in astrophysical, combustion, and laboratory plasma environments. The theoretical cross sections obtained for the dissociative recombination of the two ions are in good agreement with existing experimental data from storage ring experiments. PMID- 22324683 TI - Spontaneous parametric down-conversion and quantum walks in arrays of quadratic nonlinear waveguides. AB - We analyze the process of photon-pair generation with simultaneous quantum walks in a quadratic nonlinear waveguide array. We demonstrate that the spontaneous parametric down-conversion in the array allows for creating quantum states with strongly pronounced spatial correlations, which are qualitatively different from those possible in bulk crystals or through quantum walks in linear waveguide arrays. Most importantly, the photon correlations can be controlled entirely classically by varying the spatial profile of the pump beam or the phase-matching conditions. PMID- 22324684 TI - Collective quantum jumps of Rydberg atoms. AB - We study an open quantum system of atoms with a long-range Rydberg interaction, laser driving, and spontaneous emission. Over time, the system occasionally jumps between a state of low Rydberg population and a state of high Rydberg population. The jumps are inherently collective, and in fact, exist only for a large number of atoms. We explain how entanglement and quantum measurement enable the jumps, which are otherwise classically forbidden. PMID- 22324685 TI - Broadband light harvesting nanostructures robust to edge bluntness. AB - Metallic structures with sharp corners harvest the energy of incident light through plasmonic resonances, concentrating it in the corners and greatly increasing the local energy density. Despite its wide array of applications, this effect is normally strongly dependent on how sharp the corners are, presenting problems for fabrication. In this Letter, an analytical approach is proposed, based on transformation optics, to investigate a general class of plasmonic nanostructures with blunt edges or corners. Comprehensive discussions are provided on how the geometry affects the local field enhancement as well as the frequency and energy of each plasmonic resonance. Remarkably, our results evidence the possibility of designing broadband light harvesting devices with an absorption property insensitive to the geometry bluntness. PMID- 22324686 TI - PT symmetry and spontaneous symmetry breaking in a microwave billiard. AB - We demonstrate the presence of parity-time (PT) symmetry for the non-Hermitian two-state Hamiltonian of a dissipative microwave billiard in the vicinity of an exceptional point (EP). The shape of the billiard depends on two parameters. The Hamiltonian is determined from the measured resonance spectrum on a fine grid in the parameter plane. After applying a purely imaginary diagonal shift to the Hamiltonian, its eigenvalues are either real or complex conjugate on a curve, which passes through the EP. An appropriate basis choice reveals its PT symmetry. Spontaneous symmetry breaking occurs at the EP. PMID- 22324687 TI - Ultimate turbulent Taylor-Couette flow. AB - The flow structure of strongly turbulent Taylor-Couette flow with Reynolds numbers up to Re(i)=2*10(6) of the inner cylinder is experimentally examined with high-speed particle image velocimetry (PIV). The wind Reynolds numbers Re(w) of the turbulent Taylor-vortex flow is found to scale as Re(w)?Ta(1/2), exactly as predicted by Grossmann and Lohse [Phys. Fluids 23, 045108 (2011).] for the ultimate turbulence regime, in which the boundary layers are turbulent. The dimensionless angular velocity flux has an effective scaling of Nu(omega)?Ta(0.38), also in correspondence with turbulence in the ultimate regime. The scaling of Nu(omega) is confirmed by local angular velocity flux measurements extracted from high-speed PIV measurements: though the flux shows huge fluctuations, its spatial and temporal average nicely agrees with the result from the global torque measurements. PMID- 22324688 TI - Transition to the ultimate state of turbulent Rayleigh-Benard convection. AB - Measurements of the Nusselt number Nu and of a Reynolds number Re(eff) for Rayleigh-Benard convection (RBC) over the Rayleigh-number range 10(12)?Ra?10(15) and for Prandtl numbers Pr near 0.8 are presented. The aspect ratio Gamma=D/L of a cylindrical sample was 0.50. For Ra?10(13) the data yielded Nu?Ra(gamma(eff)) with gamma(eff)?0.31 and Re(eff)?Ra(zeta(eff)) with zeta(eff)?0.43, consistent with classical turbulent RBC. After a transition region for 10(13)?Ra?5*10(14), where multistability occurred, we found gamma(eff)?0.38 and zeta(eff)=zeta?0.50, in agreement with the results of Grossmann and Lohse for the large-Ra asymptotic state with turbulent boundary layers which was first predicted by Kraichnan. PMID- 22324689 TI - Single shot spatial and temporal coherence properties of the SLAC Linac Coherent Light Source in the hard x-ray regime. AB - We measured the transverse and longitudinal coherence properties of the Linac Coherent Light Source (LCLS) at SLAC in the hard x-ray regime at 9 keV photon energy on a single shot basis. Speckle patterns recorded in the forward direction from colloidal nanoparticles yielded the transverse coherence properties of the focused LCLS beam. Speckle patterns from a gold nanopowder recorded with atomic resolution allowed us to measure the shot-to-shot variations of the spectral properties of the x-ray beam. The focused beam is in the transverse direction fully coherent with a mode number close to 1. The average number of longitudinal modes behind the Si(111) monochromator is about 14.5 and the average coherence time tau(c)=(2.0+/-1.0) fc. The data suggest a mean x-ray pulse duration of (29+/ 14) fs behind the monochromator for (100+/-14) fc electron pulses. PMID- 22324690 TI - Evidence of high harmonics from echo-enabled harmonic generation for seeding x ray free electron lasers. AB - Echo-enabled harmonic generation free electron lasers hold great promise for the generation of fully coherent radiation in x-ray wavelengths. Here we report the first evidence of high harmonics from the echo-enabled harmonic generation technique in the realistic scenario where the laser energy modulation is comparable to the beam slice energy spread. In this experiment, coherent radiation at the seventh harmonic of the second seed laser is generated when the energy modulation amplitude is about 2-3 times the slice energy spread. The experiment confirms the underlying physics of echo-enabled harmonic generation and may have a strong impact on emerging seeded x-ray free electron lasers that are capable of generating laserlike x rays which will advance many areas of science. PMID- 22324691 TI - Impeding hohlraum plasma stagnation in inertial-confinement fusion. AB - This Letter reports the first time-gated proton radiography of the spatial structure and temporal evolution of how the fill gas compresses the wall blowoff, inhibits plasma jet formation, and impedes plasma stagnation in the hohlraum interior. The potential roles of spontaneously generated electric and magnetic fields in the hohlraum dynamics and capsule implosion are discussed. It is shown that interpenetration of the two materials could result from the classical Rayleigh-Taylor instability occurring as the lighter, decelerating ionized fill gas pushes against the heavier, expanding gold wall blowoff. This experiment showed new observations of the effects of the fill gas on x-ray driven implosions, and an improved understanding of these results could impact the ongoing ignition experiments at the National Ignition Facility. PMID- 22324692 TI - Dispersive nature of high mach number collisionless plasma shocks: Poynting flux of oblique whistler waves. AB - Whistler wave trains are observed in the foot region of high Mach number quasiperpendicular shocks. The waves are oblique with respect to the ambient magnetic field as well as the shock normal. The Poynting flux of the waves is directed upstream in the shock normal frame starting from the ramp of the shock. This suggests that the waves are an integral part of the shock structure with the dispersive shock as the source of the waves. These observations lead to the conclusion that the shock ramp structure of supercritical high Mach number shocks is formed as a balance of dispersion and nonlinearity. PMID- 22324693 TI - High-gain magnetized inertial fusion. AB - Magnetized inertial fusion (MIF) could substantially ease the difficulty of reaching plasma conditions required for significant fusion yields, but it has been widely accepted that the gain is not sufficient for fusion energy. Numerical simulations are presented showing that high-gain MIF is possible in cylindrical liner implosions based on the MagLIF concept [S. A. Slutz et al Phys. Plasmas 17, 056303 (2010)] with the addition of a cryogenic layer of deuterium-tritium (DT). These simulations show that a burn wave propagates radially from the magnetized hot spot into the surrounding much denser cold DT given sufficient hot-spot areal density. For a drive current of 60 MA the simulated gain exceeds 100, which is more than adequate for fusion energy applications. The simulated gain exceeds 1000 for a drive current of 70 MA. PMID- 22324694 TI - Opposite effect of spin-orbit coupling on condensation and superfluidity. AB - We investigate the effects of Rashba-type spin-orbit coupling (SOC) on the condensed density and superfluid density tensor of a two-component Fermi gas in the BCS-BEC crossover at zero temperature. In anisotropic three dimensions (3D), we find that SOC has an opposite effect on condensation (enhanced) and superfluidity (suppressed in the SOC direction), and this effect becomes most pronounced for very weak interactions and the SOC strength being larger than a characteristic value. Furthermore, as functions of SOC strength, the condensed density changes monotonically for all interaction parameters, while the superfluid density has a minimum when the interaction parameter is below a critical value. We also discuss the isotropic two-dimensional case where analytical expressions for the gap and number equations are obtained and the same phenomena are found as that of the 3D case. PMID- 22324695 TI - Strong suppression of the Kosterlitz-Thouless transition in a 4He film under high pressure. AB - We have found that the surface specularity for 3He quasiparticle scattering is closely related to the superfluidity and the Kosterlitz-Thouless (KT) transition of 4He film adsorbed on the surface. The specularity is determined by measurements of the transverse acoustic impedance of bulk liquid 3He. The unique point of our system is that we can control the correlation among 4He atoms in the film by changing the pressure of the bulk 3He. The observed KT transition temperature is significantly suppressed by increasing the pressure, which suggests a strong correlation effect on KT transition. PMID- 22324696 TI - Irradiation-induced formation of nanocrystallites with C15 Laves phase structure in bcc iron. AB - A three-dimensional periodic structure is proposed for self-interstitial clusters in body-centered-cubic metals, as opposed to the conventional two-dimensional loop morphology. The underlying crystal structure corresponds to the C15 Laves phase. Using density functional theory and interatomic potential calculations, we demonstrate that in alpha-iron these C15 aggregates are highly stable and immobile and that they exhibit large antiferromagnetic moments. They form directly in displacement cascades, and they can grow by capturing self interstitials. They thus constitute an important new element to account for when predicting the microstructural evolution of iron base materials under irradiation. PMID- 22324697 TI - Heterogeneous crystal nucleation: the effect of lattice mismatch. AB - A simple dynamical density functional theory is used to investigate freezing of an undercooled liquid in the presence of a crystalline substrate. We find that the adsorption of the crystalline phase on the substrate, the contact angle, and the height of the nucleation barrier are nonmonotonic functions of the lattice constant of the substrate. We show that the free-growth-limited model of particle induced freezing by Greer et al. [Acta Mater. 48, 2823 (2000)] is valid for larger nanoparticles and a small anisotropy of the interface free energy. Faceting due to the small size of the foreign particle or a high anisotropy decouples free growth from the critical size of homogeneous nuclei. PMID- 22324698 TI - Coverage-dependent collective diffusion of a dense Pb wetting layer on Si(111). AB - The dynamics of a dense Pb wetting layer on the Si(111) surface is studied in the framework of a generalized Frenkel-Kontorova model. Instead of the typical diffusion by random hopping processes, a liquidlike collective motion of the Pb atoms within the dense wetting layer is revealed to give rise to ultrafast kinetics of the wetting layer even at low temperatures. A kinetic Monte Carlo simulation including this collective spreading mechanism of the dense wetting layer quantitatively reproduces the experimental observations. PMID- 22324699 TI - Insulator-to-metal transition in selenium-hyperdoped silicon: observation and origin. AB - Hyperdoping has emerged as a promising method for designing semiconductors with unique optical and electronic properties, although such properties currently lack a clear microscopic explanation. Combining computational and experimental evidence, we probe the origin of sub-band-gap optical absorption and metallicity in Se-hyperdoped Si. We show that sub-band-gap absorption arises from direct defect-to-conduction-band transitions rather than free carrier absorption. Density functional theory predicts the Se-induced insulator-to-metal transition arises from merging of defect and conduction bands, at a concentration in excellent agreement with experiment. Quantum Monte Carlo calculations confirm the critical concentration, demonstrate that correlation is important to describing the transition accurately, and suggest that it is a classic impurity-driven Mott transition. PMID- 22324700 TI - CeB6 macroscopically revisited. AB - Magnetic susceptibility anisotropy and high sensitivity magnetostriction measurements are used to investigate the symmetry of CeB(6) ordered states. The antiferromagnetic state is confirmed as tetragonal, but no deviation from the cubic symmetry is observed in the so-called antiferroquadrupolar phase, where only volume effects are detected. In this phase, the temperature dependence of the strain field susceptibilities is typical of nonordered quadrupoles. Moreover, while an antiferroquadrupolar order should be cubic, this symmetry is incompatible with the (1/21/21/2) ordering wave vector. The antiferroquadrupolar description of CeB(6) phase II is clearly inconsistent, and an alternative model, based on a unidimensional representation of the cube, has to be sought. PMID- 22324701 TI - Experimental and theoretical evidence for pressure-induced metallization in FeO with rocksalt-type structure. AB - Electrical conductivity of FeO was measured up to 141 GPa and 2480 K in a laser heated diamond-anvil cell. The results show that rock-salt (B1) type structured FeO metallizes at around 70 GPa and 1900 K without any structural phase transition. We computed fully self-consistently the electronic structure and the electrical conductivity of B1 FeO as a function of pressure and temperature, and found that although insulating as expected at ambient condition, B1 FeO metallizes at high temperatures, consistent with experiments. The observed metallization is related to spin crossover. PMID- 22324702 TI - Effect of miscibility and percolation on electron transport in amorphous poly(3 hexylthiophene)/phenyl-C61-butyric acid methyl ester blends. AB - Recent evidence has demonstrated that amorphous mixed phases are ubiquitous within mesostructured polythiophene-fullerene mixtures. Nevertheless, the role of mixing within nanophases on charge transport of organic semiconductor mixtures is not fully understood. To this end, we have examined the electron mobility in amorphous blends of poly(3-hexylthiophene) and phenyl-C(61)-butyric acid methyl ester. Our studies reveal that the miscibility of the components strongly affects electron transport within blends. Immiscibility promotes efficient electron transport by promoting percolating pathways within organic semiconductor mixtures. As a consequence, partial miscibility may be important for efficient charge transport in polythiophene-fullerene mixtures and organic solar cell performance. PMID- 22324703 TI - Plasmonic coherent drive of an optical trap. AB - We demonstrate that optical trapping can be driven by delocalized surface plasmon modes resonantly excited within a standing wave trap. Dynamical modifications are shown to be determined by the near-field symmetry of the plasmonic modes with negligible thermal effect. With low trapping powers and polarization control, remarkable stiffness enhancements are recorded, the larger the smaller the particle. The results can be simply modeled accounting for a coherent interaction between the plasmon field and the Gaussian standing wave of the trap. PMID- 22324704 TI - Cross-correlated responses of topological superconductors and superfluids. AB - We study nontrivial responses of topological superconductors and superfluids to the temperature gradient and rotation of the system. In two-dimensional gapped systems, the Streda formula for the electric Hall conductivity is generalized to the thermal Hall conductivity. Applying this formula to the Majorana surface states of three-dimensional topological superconductors predicts cross-correlated responses between the orbital angular momentum and thermal polarization (entropy polarization). These results can be naturally related to the gravitoelectromagnetism description of three-dimensional topological superconductors and superfluids, analogous to the topological magnetoelectric effect in Z(2) topological insulators. PMID- 22324705 TI - Heat-capacity measurements of energy-gap nodes of the heavy-fermion superconductor CeIrIn5 deep inside the pressure-dependent dome structure of its superconducting phase diagram. AB - We use heat-capacity measurements as a function of field rotation to identify the nodal gap structure of CeIrIn(5) at pressures to 2.05 GPa, deep inside its superconducting dome. A fourfold oscillation in the heat capacity at 0.3 K is observed for all pressures, but with its sign reversed between 1.50 and 0.90 GPa. On the basis of recent theoretical models for the field-angle-dependent specific heat, all data, including the sign reversal, imply a d(x(2)-y(2)) order parameter with nodes along [110], which constrains theoretical models of the pairing mechanism in CeIrIn(5). PMID- 22324706 TI - Genetic-algorithm discovery of a direct-gap and optically allowed superstructure from indirect-gap Si and Ge semiconductors. AB - Combining two indirect-gap materials-with different electronic and optical gaps to create a direct gap material represents an ongoing theoretical challenge with potentially rewarding practical implications, such as optoelectronics integration on a single wafer. We provide an unexpected solution to this classic problem, by spatially melding two indirect-gap materials (Si and Ge) into one strongly dipole allowed direct-gap material. We leverage a combination of genetic algorithms with a pseudopotential Hamiltonian to search through the astronomic number of variants of Si(n)/Ge(m)/.../Si(p)/Ge(q) superstructures grown on (001) Si(1-x)Ge(x). The search reveals a robust configurational motif-SiGe(2)Si(2)Ge(2)SiGe(n) on (001) Si(x)Ge(1-x) substrate (x<=0.4) presenting a direct and dipole-allowed gap resulting from an enhanced Gamma-X coupling at the band edges. PMID- 22324707 TI - Why nanoprojectiles work differently than macroimpactors: the role of plastic flow. AB - Atomistic simulation data on crater formation due to the hypervelocity impact of nanoprojectiles of up to 55 nm diameter and with targets containing up to 1.1*10(10) atoms are compared to available experimental data on MUm-, mm-, and cm sized projectiles. We show that previous scaling laws do not hold in the nanoregime and outline the reasons: within our simulations we observe that the cratering mechanism changes, going from the smallest to the largest simulated scales, from an evaporative regime to a regime where melt and plastic flow dominate, as is expected in larger microscale experiments. The importance of the strain-rate dependence of strength and of dislocation production and motion are discussed. PMID- 22324708 TI - Nuclear spins of ionized phosphorus donors in silicon. AB - We demonstrate the coherent control and electrical readout of ionized phosphorus donor nuclear spins in (nat)Si. By combining time-programed optical excitation with coherent electron spin manipulation, we selectively ionize the donors depending on their nuclear spin state, exploiting a spin-dependent recombination process at the Si/SiO(2) interface, and find a nuclear spin coherence time of 18 ms for the ionized donors. The presented technique allows for spectroscopy of ionized-donor nuclear spins and enhances the sensitivity of electron nuclear double resonance to a level of 3000 nuclear spins. PMID- 22324709 TI - Cold-field switching in PVDF-TrFE ferroelectric polymer nanomesas. AB - Polarization reversal in ferroelectric nanomesas of polyvinylidene fluoride with trifluoroethylene has been probed by ultrahigh vacuum piezoresponse force microscopy in a wide temperature range from 89 to 326 K. In dramatic contrast to the macroscopic data, the piezoresponse force microscopy local switching was nonthermally activated and, at the same time, occurring at electric fields significantly lower than the intrinsic switching threshold. A "cold-field" defect mediated extrinsic switching is shown to be an adequate scenario describing this peculiar switching behavior. The extrinsic character of the observed polarization reversal suggests that there is no fundamental bar for lowering the coercive field in ferroelectric polymer nanostructures, which is of importance for their applications in functional electronics. PMID- 22324710 TI - Surface-surface interaction in smectic liquid crystal films. AB - Null transmission ellipsometry was employed to study the field induced transition of the surface arrangements in freestanding films of smectic liquid crystals. The interlayer interaction between the two surfaces obtained from the threshold voltage for the transition is found to be antiferroelectric and is quasilong ranged. The possible microscopic origins of the measured interaction and its relevance to the interlayer interaction in antiferroelectric liquid crystal materials are discussed. PMID- 22324711 TI - Synaptic bistability due to nucleation and evaporation of receptor clusters. AB - We introduce a bistability mechanism for long-term synaptic plasticity based on switching between two metastable states that contain significantly different numbers of synaptic receptors. One state is characterized by a two-dimensional gas of mobile interacting receptors and is stabilized against clustering by a high nucleation barrier. The other state contains a receptor gas in equilibrium with a large cluster of immobile receptors, which is stabilized by the turnover rate of receptors into and out of the synapse. Transitions between the two states can be initiated by either an increase (potentiation) or a decrease (depotentiation) of the net receptor flux into the synapse. This changes the saturation level of the receptor gas and triggers nucleation or evaporation of receptor clusters. PMID- 22324712 TI - Optimal intermittence in search strategies under speed-selective target detection. AB - Random search theory has been previously explored for both continuous and intermittent scanning modes with full target detection capacity. Here we present a new class of random search problems in which a single searcher performs flights of random velocities, the detection probability when it passes over a target location being conditioned to the searcher speed. As a result, target detection involves an N-passage process for which the mean search time is here analytically obtained through a renewal approximation. We apply the idea of speed-selective detection to random animal foraging since a fast movement is known to significantly degrade perception abilities in many animals. We show that speed selective detection naturally introduces an optimal level of behavioral intermittence in order to solve the compromise between fast relocations and target detection capability. PMID- 22324713 TI - How changes in cell mechanical properties induce cancerous behavior. AB - Tumor growth and metastasis are ultimately mechanical processes involving cell migration and uncontrolled division. Using a 3D discrete model of cells, we show that increased compliance as observed for cancer cells causes them to grow at a much faster rate compared to surrounding healthy cells. We also show how changes in intercellular binding influence tumor malignancy and metastatic potential. These findings suggest that changes in the mechanical properties of cancer cells is the proximate cause of uncontrolled division and migration and various biochemical factors drive cancer progression via this mechanism. PMID- 22324714 TI - Margination of white blood cells in microcapillary flow. AB - Margination of white blood cells (WBCs) towards vessel walls is an essential precondition for their efficient adhesion to the vascular endothelium. We perform numerical simulations with a two-dimensional blood flow model to investigate the dependence of WBC margination on hydrodynamic interactions of blood cells with the vessel walls, as well as on their collective behavior and deformability. We find WBC margination to be optimal in intermediate ranges of red blood cell (RBC) volume fractions and flow rates, while, beyond these ranges, it is substantially attenuated. RBC aggregation enhances WBC margination, while WBC deformability reduces it. These results are combined in state diagrams, which identify WBC margination for a wide range of flow and cell suspension conditions. PMID- 22324715 TI - Dynamics on the laminar-turbulent boundary and the origin of the maximum drag reduction asymptote. AB - Dynamical trajectories on the boundary in state space between laminar and turbulent plane channel flow-edge states-are computed for Newtonian and viscoelastic fluids. Viscoelasticity has a negligible effect on the properties of these solutions, and, at least at a low Reynolds number, their mean velocity profiles correspond closely to experimental observations for polymer solutions in the maximum drag reduction regime. These results confirm the existence of weak turbulence states that cannot be suppressed by polymer additives, explaining the fact that there is an upper limit for polymer-induced drag reduction. PMID- 22324716 TI - Shear banding in molecular dynamics of polymer melts. AB - In order to establish constitutive equations for a viscoelastic fluid uniform shear flow is usually required. However, in the last 10 years S. Q. Wang and co workers have demonstrated that some entangled polymers do not flow with the uniform shear rate as usually assumed, but instead choose to separate into fast and slow flowing regions. This phenomenon, known as shear banding, causes flow instabilities and in principle invalidates all rheological measurements when it occurs. In this Letter we report the first observation of shear banding in molecular dynamics simulations of entangled polymer melts. We show that our observations are in a very good agreement with the phenomenology developed by Fielding and Olmsted. Our findings provide a simple way of validating the empirical macroscopic phenomenology of shear banding. PMID- 22324717 TI - Active nonlinear microrheology in a glass-forming Yukawa fluid. AB - A molecular dynamics computer simulation of a glass-forming Yukawa mixture is used to study the anisotropic dynamics of a single particle pulled by a constant force. Beyond linear response, a scaling regime is found where a force temperature superposition principle of a Peclet number holds. In the latter regime, the diffusion dynamics perpendicular to the force can be mapped on the equilibrium dynamics in terms of an effective temperature, whereas parallel to the force a superdiffusive behavior is seen in the long-time limit. This behavior is associated with a hopping motion from cage to cage and can be qualitatively understood by a simple trap model. PMID- 22324718 TI - Comment on "Extremely correlated Fermi liquids". PMID- 22324720 TI - Topical tacrolimus significantly promotes repigmentation in idiopathic guttate hypomelanosis: a double-blind, randomized, placebo-controlled study. AB - BACKGROUND: Idiopathic guttate hypomelanosis (IGH) is an idiopathic disorder affecting a large number of people. Effective treatments are not yet available. Objectives To investigate the efficacy of topical 0.1% tacrolimus ointment compared with placebo in the treatment of IGH. MATERIALS AND METHODS: Twenty-six patients were included in the study. Lesions on one side of the body were selected to have a treatment with 0.1% tacrolimus ointment, whereas those on the other side served as a control with placebo ointment that had the same physical appearance. Colorimeter was used to assess skin colour at baseline and at 1, 2, 3, 4 and 6 months of treatment. RESULTS: Mean luminosity scale after adjusted for baseline from the treated side gradually decreased and reached statistical significance compared with the control group after 6 months of treatment (P = 0.019). Physicians' improvement grading score showed that 11% of the patients demonstrated improvement of their skin lesions on the treated side after 6 months' treatment. CONCLUSION: Topical 0.1% tacrolimus ointment appeared to be an effective and safe treatment for IGH. The improvements were best observed by colorimetry, yet, they were not statistically significant upon clinical assessments. PMID- 22324721 TI - Hydroxycinnamic acid ethyl esters as precursors to ethylphenols in wine. AB - A method for determining ethyl coumarate and ethyl ferulate in wine using GC-MS with deuterium-labeled analogues has been developed and used to measure the evolution of these two esters during the production of two commercial monovarietal red wines, cv. Grenache and Shiraz. During fermentation, the concentration of ethyl coumarate rose from low levels to 0.4 mg/L in Grenache and 1.6 mg/L in Shiraz wines. These concentrations then increased further during barrel aging to 1.4 and 3.6 mg/L, respectively. The concentration of ethyl ferulate was much lower, reaching a maximum of only 0.09 mg/L. Conversion of ethyl coumarate and ethyl ferulate to their corresponding ethylphenols was observed during fermentations of a synthetic medium with two strains of Dekkera bruxellensis (AWRI 1499 and AWRI 1608), while a third (strain AWRI 1613) produced no ethylphenols at all from these precursors. Strains AWRI 1499 and 1608 produced 4-ethylphenol from ethyl coumarate in 68% and 57% yields, respectively. The corresponding yields of 4-ethylguaiacol from ethyl ferulate were much lower, 7% and 3%. Monitoring of ethyl coumarate and ethyl ferulate concentration during the Dekkera fermentations showed that the selectivity for ethylphenol production according to yeast strain and the precursor was principally a result of variation in esterase activity. Consequently, ethyl coumarate can be considered to be a significant precursor to 4-ethylphenol in wines affected by these two strains of Brettanomyces/Dekkera yeast, while ethyl ferulate is not an important precursor to 4-ethylguaiacol. PMID- 22324724 TI - The description of population vulnerability in quantitative risk analysis. AB - The description of the distribution of population in the potential impact areas of accident scenarios is of utmost importance for the assessment of the final consequences of potential accidents. Vulnerability centers (i.e., sites where the simultaneous presence of a relevant number of persons in a narrow area is anticipated) may play an important role in this framework. In this study a method for the correct and detailed description of offsite target population in potential impact areas of major accidents is developed. The method is aimed at supporting quantitative risk analysis studies, emergency planning, and land-use planning. An approach is suggested to define the population categories that should be taken into account and to provide criteria for indoor and outdoor population distribution in vulnerability centers. Case studies are also provided to understand the outcomes and the potentialities of the methodology. PMID- 22324723 TI - Antineoplastic agents. 548. Synthesis of iodo- and diiodocombstatin phosphate prodrugs. AB - Toward the objective of designing a structurally modified analogue of the combretastatin A-4 phosphate prodrug (1b) with the potential for increased specificity toward thyroid carcinoma, synthesis of a series of iodocombstatin phosphate (11a-h) and diiodocombstatin phosphate prodrugs (12a-h) has been accomplished. The diiodo series was obtained via 8a and 9c from condensation of 4 and 6, and the iodo sequence involved a parallel pathway. Both series of iodocombstatins were found to display significant to powerful inhibition of the growth of a panel of human cancer cell lines and of the murine P388 lymphocytic leukemia cell line. Of the diiodo series, 12a was also found to markedly inhibit growth of pediatric neuroblastoma, and monoiodocombstatin 9a strongly inhibited HUVEC growth. Overall, the strongest activity was found against the breast, CNS, leukemia, lung, and prostate cancer cell lines and the least activity against the pancreas and colon lines. Parallel biological investigations of tubulin interaction, antiangiogenesis, and antimicrobial effects were also conducted. PMID- 22324725 TI - High-performance plastic dye-sensitized solar cells based on low-cost commercial P25 TiO2 and organic dye. AB - High-performance plastic dye-sensitized solar cells (DSCs) based on low-cost commercial Degussa P25 TiO(2) and organic indoline dye D149 have been fabricated using electrophoretic deposition (EPD) with compression post-treatment at room temperature. The pressed EPD electrode outperformed the sintered EPD electrode and as-prepared EPD electrode in short-circuit current density and power conversion efficiency. About 150% and 180% enhancement in power conversion efficiency have been achieved in DSC devices with sintering and compression post treatment as compared to the as-prepared electrode, respectively. Several characterizations including intensity modulated photocurrent spectroscopy, incident photon-to-electron conversion efficiency and electrochemical impedance spectra have been employed to reveal the nature of improvement with post treatment. Experimental results indicate that the sintering and compression post treatment are beneficial to improve the electron transport and thus lead to the enhancement of photocurrent and power conversion efficiency. In addition, the compression post-treatment is more efficient than sintering post-treatment in improving interparticle connection in the as-prepared EPD electrode. Under optimized conditions, the conversion efficiency of plastic devices with D149 sensitized P25 TiO(2) photoanode has reached 5.76% under illumination of AM 1.5G (100 mW cm(-2)). This study demonstrates that the EPD combined with compression post-treatment provides a way to fabricate highly efficient plastic photovoltaic devices. PMID- 22324726 TI - An understanding of the modulation of photophysical properties of curcumin inside a micelle formed by an ionic liquid: a new possibility of tunable drug delivery system. AB - The present study reveals the modulation of photophysical properties of curcumin, an important drug for numerous reasons, inside a micellar environment formed by a surfactant-like ionic liquid (IL-micelle) in aqueous solution. Higher stability of the drug inside IL-micelle in the absence and presence of a simple salt (sodium chloride) as well as considerably large partition coefficient (K(p) = 8.59 * 10(3)) to the micellar phase from water make this system a well behaved drug loading vehicle. Remarkable change in fluorescence intensity with a strong blue-shift implies the gradual perturbation of intramolecular hydrogen bond (H bond) present within the keto-enol group of curcumin along with considerable formation of intermolecular H-bond between curcumin and the headgroup of surfactant-like IL. Very fast nonradiative decay channels in curcumin mainly caused by the excited state intramolecular proton transfer (ESIPT) are thus depleted remarkably in the presence of IL-micelle of reduced polarity and as a result of restricted rotational and vibrational degrees of freedom when bound to the micelle. Moreover, time-resolved results confirm that not only the keto-enol group of curcumin is playing here but also the phenolic hydroxyl groups are also responsible for such modulation in photophysical properties. From a thermodynamic point of view, our system shows good correlation with its stability parameters (higher binding constant with very less hydrolytic degradation rate ~1%) and higher negative value of binding enthalpy of interaction (-DeltaH) than total free energy change (-DeltaG) implies that the nature of binding interaction is enthalpy driven not entropy alone. Summarizing all the above observations, we have concluded that the modulation of the intramolecular proton transfer is due to the presence of both intermolecular proton transfer as well as strong hydrophobic interaction between curcumin and the IL-micelle. PMID- 22324727 TI - Acetaldehyde oral self-administration: evidence from the operant-conflict paradigm. AB - BACKGROUND: Acetaldehyde (ACD), ethanol's first metabolite, has been reported to interact with the dopaminergic reward system, and with the neural circuits involved in stress response. Rats self-administer ACD directly into cerebral ventricles, and multiple intracerebroventricular infusions of ACD produce conditioned place preference. Self-administration has been largely employed to assess the reinforcing and addictive properties of most drugs of abuse. In particular, operant conditioning is a valid model to investigate drug-seeking and drug-taking behavior in rats. METHODS: This study was aimed at the evaluation of (i) the motivational properties of oral ACD in the induction and maintenance of an operant-drinking behavior; (ii) ACD effect in a conflict situation employing the punishment-based Geller-Seifter procedure; and (iii) the onset of a relapse drinking behavior, following ACD deprivation. The lever-pressing procedure in a sound-attenuated operant-conditioning chamber was scheduled into 3 different periods: (i) training-rewarded responses with a fixed ratio 1; (ii) conflict rewarded responses periodically associated with a 0.2 mA foot-shock; and (iii) relapse-rewarded lever presses following 1-week ACD abstinence. RESULTS: Our results show that oral self-administrated ACD induced: a higher rate of punished responses in Geller-Seifter procedures; and the establishment of a relapse behavior following ACD deprivation. CONCLUSIONS: In conclusion, our results indicate that ACD is able to induce an operant-drinking behavior, which is also maintained besides the conflict procedure and enhanced by the deprivation effect, supporting the hypothesis that ACD itself possesses motivational properties, such as alcohol and other substances of abuse. PMID- 22324728 TI - Evidence-based electroconvulsive therapy. PMID- 22324729 TI - The challenge of uncovering the genetics of anxiety: an editorial comment to Arias B, Aguilera M, Moya J et al. 'The role of genetic variability in the SLC6A4, BDNF and GABRA6 genes in anxiety-related traits' (2). PMID- 22324730 TI - Socioeconomic status and mental health: what is the causal relationship?: editorial comment to Kristian Tambs et al. 'Genetic and environmental contributions to the relationship between education and anxiety disorders. A twin study' (1). PMID- 22324731 TI - Biography of J.-O. Ottosson. PMID- 22324732 TI - History of Norwegian psychiatry. AB - Psychiatry as a professional and scientific enterprise developed in Norway in the middle of the 19th century. During the last part of this century, four state asylums were erected, followed by several county asylums during the first part of the 20th century. From the 1870 s, institutions for private care were established, usually in the vicinity of the asylums. During the middle of the 19th century, psychiatry in Norway was influenced by "moral treatment", but during the end of the century somatic ideas prevailed. After the Second World War, Norwegian psychiatry was influenced by Dutch and British social psychiatry, followed by American psychoanalytic-oriented psychiatry during the 1960-70s. Since the 1980s, the climate changed, with more emphasis on classification and drug therapy. The new American DSM-III also influenced Norwegian psychiatry, and cognitive-behavioral therapies became more prevalent. Norwegian psychiatric research has during the last few decades been characterized by epidemiological studies, clinical follow-ups and twin research. PMID- 22324733 TI - Important elements in farm animal-assisted interventions for persons with clinical depression: a qualitative interview study. AB - PURPOSE: The main aim of this study was to obtain participants' own experience of a farm animal-assisted intervention, and what they perceived as important elements in relation to their mental health. METHOD: A qualitative study, inspired by a phenomenological-hermeneutical perspective was conducted. Eight persons with clinical depression who had completed a 12-week farm animal-assisted intervention at a dairy farm participated in thematic interviews between May and June 2009. RESULTS: The intervention was regarded as a positive experience for the participants. The analyses revealed that central elements in the intervention were the possibility to experience an ordinary work life, but also the importance of a distraction to their illness. Furthermore, the flexibility of the intervention made it possible to adjust the intervention to the participants' shifting reality and was thereby a key element in farm animal-assisted intervention. The flexibility and adapted work tasks were important elements that the participants associated with their experience of coping. A model showing the interaction between the different elements reported as important by the participants was constructed. CONCLUSIONS: This study shows that a farm animal assisted intervention could be a supplement in mental health rehabilitation. All the elements in our model could possibly influence positively on mental health. PMID- 22324734 TI - Update on immunomodulatory drugs (IMiDs) in hematologic and solid malignancies. AB - INTRODUCTION: Thalidomide and its analogs [small molecule immunomodulatory drugs (IMiDs(r))] are among the most successful new therapeutic agents of recent years. Thalidomide is now an integral part of multiple myeloma (MM) therapy. Lenalidomide has been approved for the treatment of patients with relapsed MM and 5q-myelodysplastic syndromes (MDS). Currently, more than 400 clinical trials are evaluating the activity of lenalidomide, alone or in combination with other conventional or novel therapies, in newly diagnosed MM and 5q-MDS. Based on their broad range of actions within the tumor microenvironment, IMiDs are currently also evaluated in a wide variety of additional hematologic and solid malignancies. AREAS COVERED: This paper reviews the historic development of thalidomide and its derivatives and presents novel insights into their mode of action. Moreover, it discusses up-to-date clinical trials investigating IMiDs and potential future research and therapeutic perspectives in MM and other malignancies. EXPERT OPINION: Although IMiDs have emerged as powerful agents for the treatment of hematologic and solid tumors, more preclinical and clinical studies are urgently needed both to increase our knowledge of their mechanisms of action, and to optimize their clinical use, in order to further improve the patient's quality of life and survival. PMID- 22324735 TI - Mental disorders and communication of intent to die in indigenous suicide cases, Queensland, Australia. AB - In comparing Indigenous to non-Indigenous suicide in Australia, this study focussed on the frequency of the association between some psychiatric conditions, such as depression and alcohol abuse, and some aspect of suicidality, in particular communication of suicide intent. Logistic regression was implemented to analyze cases of Indigenous (n = 471) versus non-Indigenous suicides (n = 6,655), using the Queensland Suicide Register as a data source. Compared to non Indigenous suicides, Indigenous cases had lower odds of being diagnosed with unipolar depression, seeking treatment for psychiatric conditions or leaving a suicide note. Indigenous suicides had greater odds of verbally communicating suicide intent and having a history of alcohol and substance use. The magnitude of these differences is remarkable, underscoring the need for culturally sensitive suicide prevention efforts. PMID- 22324736 TI - Retinal vessel caliber and risk factors for branch retinal vein occlusion. AB - PURPOSE: To describe the association between retinal vessel caliber and risk factors for branch retinal vein occlusion (BRVO). MATERIALS AND METHODS: We included 10,890 participants who underwent a health checkup at Kangbuk Samsung Hospital between January 2006 and December 2006. BRVO was diagnosed from retinal photographs taken for both eyes. Retinal vascular caliber measurements were performed using a computer-assisted program. Risk factors were assessed based on a patient-answered questionnaire and laboratory investigations. Logistic regression analyses were performed to identify potential risk factors for BRVO. RESULTS: The overall prevalence of BRVO was 0.8%. Among all BRVO patients, the mean central retinal artery equivalent (CRAE) was 142.59 um (+/-14.63 um), and the mean central retinal vein equivalent (CRVE) was 203.46 um (+/-18.84 um). The mean CRAE and CRVE of the control eyes were 148.15 um (+/- 15.89 um) and 211.12 um (+/-18.54 um), respectively. There were significant differences in mean CRAE and CRVE between the control group and the BRVO group (P < 0.05). Arterial hypertension was an important risk factor for BRVO (OR: 1.02 (1.01-1.03). CONCLUSIONS: Eyes with BRVO had narrow CRAE and CRVE when compared with age- and gender-matched normal eyes. Generalized attenuation of retinal vessel caliber may be characteristic of eyes with BRVO. Emphasis on blood pressure control is needed for the prevention of BRVO. PMID- 22324737 TI - A practical critique of antifungal treatment guidelines for haemato-oncologists. AB - The management of invasive fungal disease (IFD) in the haemato-oncology setting remains a challenge. This article reviews recent guidelines relating to IFD for their similarities and differences, as well as applying the Appraisal of Guidelines Research and Evaluation (AGREE) criteria. The guidelines' recommendations on antifungal prophylaxis, empirical and definitive treatment of candidiasis and aspergillosis are summarized; also, minimum standards for diagnosis and follow-up are discussed. This critique of the reviewed guidelines is a practical guide to physicians and commissioners in making local policies for IFD management. PMID- 22324738 TI - Electrochemical differentiation of epitope-specific aptamers. AB - DNA aptamers are promising immunoshielding agents that could protect oncolytic viruses (OVs) from neutralizing antibodies (nAbs) and increase the efficiency of cancer treatment. In the present Article, we introduce a novel technology for electrochemical differentiation of epitope-specific aptamers (eDEA) without selecting aptamers against individual antigenic determinants. For this purpose, we selected DNA aptamers that can bind noncovalently to an intact oncolytic virus, vaccinia virus (VACV), which can selectively replicate in and kill only tumor cells. The aptamers were integrated as a recognition element into a multifunctional electrochemical aptasensor. The developed aptasensor was used for the linear quantification of the virus in the range of 500-3000 virus particles with a detection limit of 330 virions. Also, the aptasensor was employed to compare the binding affinities of aptamers to VACV and to estimate the degree of protection of VACV using the anti-L1R neutralizing antibody in a displacement assay fashion. Three anti-VACV aptamer clones, vac2, vac4, and vac6, showed the best immunoprotection results and can be applied for enhanced delivery of VACV. Another two sequences, vac5 and vac46, exhibited high affinities to VACV without shielding it from nAb and can be further utilized in sandwich bioassays. PMID- 22324739 TI - Temperature dependence of OH(8;6) equilibration in an air-like gas ensemble. AB - We present a quantum state-resolved computational investigation of the equilibration of rovibrationally excited OH, present as the minor component in an air-like mixture of N(2) and O(2), over the temperature range 100-1200 K. Generic features of the equilibration that are present over the entire range are identified, and the increase in speed of the principal energy exchange mechanism as the temperature increases is quantified. The data demonstrate that partitioning of excess energy and angular momentum among the modes of the three different molecules is independent of the magnitude of excess energy and of its form. The rotational temperature of OH is found to vary widely over the equilibration process, varying with number of collision cycles and with initial temperature. However, at equilibration, the rotational temperature of OH is invariably the lowest of all modes of all three species present in the ensemble. This suggests that rotational temperatures of OH obtained from rotational state populations are unlikely to provide a reliable guide to other modal temperatures in ensembles of the kind we consider. PMID- 22324740 TI - Controllable synthesis of submillimeter single-crystal monolayer graphene domains on copper foils by suppressing nucleation. AB - Submillimeter single-crystal monolayer and multilayer graphene domains were prepared by an atmospheric pressure chemical vapor deposition method with suppressing nucleation on copper foils through an annealing procedure. A facile oxidation visualization method was applied to study the nucleation density and morphology of graphene domains on copper foils. Scanning electron microscopy, transmission electron microscopy, atomic force microscopy, polarized optical microscopy, and Raman spectra showed that the submillimeter graphene domains were monolayer single crystals. PMID- 22324741 TI - 3-Fold-interpenetrated uranium-organic frameworks: new strategy for rationally constructing three-dimensional uranyl organic materials. AB - The first series of 3-fold-interpenetrated uranium-organic frameworks, UOF-1 and UOF-2, have been synthesized by hydrothermal reactions of flexible semirigid carboxylic acids and uranyl nitrate. Structure analyses indicate that UOF-1 and UOF-2 possess flu and pts topologies, respectively. PMID- 22324742 TI - Alcohol taxation policy in Thailand: implications for other low- to middle-income countries. AB - AIM: Prevention of drinking initiation is a significant challenge in low- and middle-income countries that have a high prevalence of abstainers, including life time abstainers. This paper aims to encourage a debate on an alternative alcohol taxation approach used currently in Thailand, which aims specifically to prevent drinking initiation in addition to reduce alcohol-attributable harms. METHODS: Theoretical evaluation, simulation and empirical analysis. RESULT: The taxation method of Thailand, 'Two-Chosen-One' (2C1) combines specific taxation (as a function of the alcohol content) and ad valorem taxation (as a function of the price), resulting in an effective tax rate that puts a higher tax both on beverages which are preferred by heavy drinkers and on beverages which are preferred by potential alcohol consumption neophytes, compared to either taxation system alone. As a result of these unique properties of the 2C1 taxation system, our simulations indicate that 2C1 taxation leads to a lower overall consumption than ad valorem or specific taxation alone. In addition, it puts a relatively high tax on beverages attractive to young people, the majority of whom are currently abstaining. Currently, the abstention rates in Thailand are higher than expected based on its economic wealth, which could be taken as an indication that the taxation strategy is successful. CONCLUSION: 'Two-chosen-one' (2C1) taxation has the potential to simultaneously reduce alcohol consumption and prevent drinking initiation among youth; however, additional empirical evidence is needed to assess its effectiveness in terms of the public health impact in low and middle-income countries. PMID- 22324744 TI - DNA alterations of microsatellite DNA, p53, APC and K-ras in Chinese colorectal cancer patients. AB - BACKGROUND: Colorectal cancer is one of the most rapidly increasing cancers in the world, and accumulation of alterations in oncogenes, tumour suppressor genes and mismatch repair (MMR) genes contributes to colorectal tumorigenesis. Thus, we investigated the alterations of 14 microsatellite loci adjacent to MMR genes, p53, adenomatous polyposis coli (APC) and K-ras in 52 Chinese patients with colorectal cancer. MATERIALS AND METHODS: We performed fluorescent polymerase chain reaction and capillary electrophoresis to analyse microsatellite instability (MSI) and loss of heterozygosity (LOH) in microsatellite loci, which included a panel of nine dinucleotide repeats and the Bethesda consensus panel. Additionally, we screened for mutations in exons 4-9 of p53 and the mutation cluster region (MCR) in APC by DHPLC. Codons 12, 13 and 61 in K-ras were analysed using direct sequencing. All variations were confirmed using clone sequencing. RESULTS: The alteration frequency of microsatellite DNA was 55.8% (29/52). Among the microsatellites, five loci exhibited MSI and another nine loci exhibited LOH. The mutation rates of p53, APC and K-ras were 42.3%, 38.5% and 36.5%, respectively. All patients (n = 7) with liver metastasis had a mutation in p53, APC or K-ras. APC mutation was correlated with clinical stage and the presence of lymph node metastasis (P = 0.001 and P = 0.006, respectively). CONCLUSIONS> A total of 80.8% of Chinese patients with colorectal cancer show variations in microsatellite DNA, p53, APC or K-ras. It appears that these microsatellite DNA alterations could be a new biomarker for colorectal cancer. PMID- 22324745 TI - Physical observation of a thermo-morphic transition in a silicon nanowire. AB - A thermo-morphic transition of a silicon nanowire (Si-NW) is investigated in vacuum and air ambients, and notable differences are found under each ambient. In the vacuum ambient, permanent electrical breakdown occurs as a result of the Joule self-heating arising from the applied voltage across both ends of the Si NW. The resulting current abruptly declines from a maximum value at the breakdown voltage (V(BD)) to zero. In addition, the thermal conductivity of the Si-NW is extracted from the V(BD) values under the vacuum ambient and shows good agreement with previously reported results. While the breakdown of the Si-NW does not exhibit negative differential resistance under the vacuum ambient, it interestingly shows negative differential resistance with multiple resistances in the current-voltage characteristics under the air ambient, similar to the behavior of carbon nanotubes. This behavior is triggered by current-induced oxidation, which leads to the thermo-morphic transition observed by TEM analyses. Additionally, the current-induced oxidation is favorably applied to reduce the size of a Si-NW at a localized and designated point. PMID- 22324746 TI - Determination of the microbial origin of geosmin in Chinese liquor. AB - Geosmin is the major cause of the common earthy off-flavor in light-aroma type Chinese liquor and, thus, highly detrimental to the aromatic quality. To find out its origin, the evolving process of geosmin in light-aroma type liquor making was monitored, and microbial analysis of Daqu containing geosmin was carried out. The results showed that geosmin appeared in all the fermented sorghums at different fermentation periods. About 57% geosmin in the fermented sorghums was distilled into liquor. During the distillation process, the peak of geosmin concentration appeared when alcohol content was 50-60% vol. More importantly, high geosmin content was observed during the Daqu-making process. Furthermore, five Streptomyces strains were isolated from different types of Daqu used for the fermentation of light-aroma type liquor. All of them produced only geosmin as the main volatile metabolite but no 2-methylisoborneol (2-MIB). It appears that microorganisms developing in Daqu are responsible for the presence of geosmin in liquor. Because of the relatively low detection threshold estimated at 110 ng/L in 46 vol % hydroalcoholic solution, the presence of geosmin in Daqu may pose a risk for Chinese liquor producers. PMID- 22324747 TI - Electron transfer in Rhodobacter sphaeroides reaction centers containing Zn bacteriochlorophylls: a hole-burning study. AB - Nonresonant and resonant transient, photochemical hole-burned (HB) spectra are presented for primary electron donor states of a novel bacterial reaction center (Zn-RC) of Rhodobacter sphaeroides, containing six Zn-bacteriochlorophylls (Zn BChls). A "Zn-beta-RC" in which the Zn-BChl in the bacteriopheophytin (BPhe) binding site on the A side (H(A)) has the Zn penta-coordinated, was also studied. The fifth ligand comes from a histidine introduced by site-directed mutagenesis. Formation of the P(+)Q(A)(-) state was observed in both types of RC, although under identical experimental conditions a significantly deeper P(-) band (corresponding to the lower-energy, special pair, excitonic component) was revealed in the Zn-RC. Assuming a similar lifetime of the P(+)Q(A)(-) state, the quantum yield of P(+)Q(A)(-) formation decreased by ~60% in the Zn-beta-RC (compared to the Zn-RC), as was seen in a comparison of analogous (Mg) BChl containing wild type and beta-RCs of Rb. sphaeroides [Kirmaier et al. Science1991, 251, 922]. However, the average (weakly frequency-dependent) low temperature electron transfer (ET) rates of the Zn-RC and Zn-beta-RC (measured from zero phonon holes in resonant transient HB spectra) were both ~1 ps and similar to a rate previously measured in the Rb. sphaeroides native RC [Johnson et al. J. Phys. Chem. 1989, 93, 5953]. Electron transfer rates observed in this work on the Zn-RC yielded a P870* decay rate in good agreement with recent room temperature, time-domain data [Lin et al. Proc. Natl. Acad. Sci. 2009, 106, 8537]. A lack of correlation observed between the holes near 810 and 883 nm, accounting for electrochromically induced shifts of the Zn-BChl transitions in the B(A,B) and H(A,B) binding sites, produced by formation of the P(+)BHQ(A)(-) state, indicates that the 810 nm bleach does not correspond to the P(+) (upper excitonic component of the dimer) band and is mostly contributed to by a shift of the B(B) absorption band. ZPH-action spectra indicated inhomogeneous broadening (Gamma(inh)) of ~110 cm(-1) (Zn-RC) and ~130 cm(-1) (Zn-beta-RC). Experimentally determined Gamma(inh) decreased the number of variables in theoretical fits of the absorption and frequency-dependent shapes of resonant HB spectra, leading to more reliable Huang-Rhys factors for both low-frequency phonons and a pseudolocalized phonon, omega(SP), often referred to as the special pair marker mode. PMID- 22324748 TI - High-risk driving behaviors among adolescent binge drinkers. AB - BACKGROUND: Binge drinking is common among adolescents. Alcohol use, particularly binge drinking, has been associated with neurocognitive deficits and increased risk-taking behaviors, which may contribute to negative driving outcomes among adolescents even while sober. OBJECTIVES: To examine potential differences in self-reported risky driving behaviors between adolescent binge drinkers and a matched sample of controls on measures of (1) compliance with graduated licensing laws, (2) high-risk driving behaviors, and (3) driving outcomes (i.e., crashes, traffic tickets). METHODS: This study examined driving behaviors and outcomes in adolescent recent binge drinkers (n = 21) and demographically and driving history matched controls (n = 17) between the ages of 16-18 years. RESULTS: Binge drinkers more frequently violated graduated licensing laws (e.g., driving late at night) and engaged in more "high-risk" driving behaviors, such as speeding and using a cell phone while driving. Binge drinkers had more traffic tickets, crashes, and "near crashes" than the control group. Speeding was the behavior most associated with crashes within the binge drinkers. CONCLUSION: In this study, binge-drinking teens consistently engage in more dangerous driving behaviors and experience more frequent crashes and traffic tickets. They are also less compliant with preventative restrictions placed on youth while they are learning critical safe driving skills. SCIENTIFIC SIGNIFICANCE: These findings highlight a need to examine the contribution of underlying traits (such as sensation seeking) and binge-related cognitive changes to these high-risk driving behaviors, which may assist researchers in establishing alternative prevention and policy efforts targeting this population. PMID- 22324749 TI - Examining the health-risk tradeoffs of mandatory bicycle helmet laws. PMID- 22324750 TI - Psychache and suicide ideation among men who are homeless: a test of Shneidman's model. AB - Suicide ideation among the homeless is 10 times more common than in the general population. Cognitive theories of depression and hopelessness propose to explain suicidality; however, as yet, none of these fully account for the phenomenon. Shneidman has suggested a theory of psychache or unbearable psychological pain to explain suicidality. This theory has found support among low-risk populations but has not been extensively tested within a high-risk population. The current research assessed the utility of psychache among men who are homeless (N = 97). In support of Shneidman's theory, analyses revealed that psychache was a stronger predictor of suicide ideation than was depression, hopelessness, or life meaning. PMID- 22324751 TI - Role of glycans and glycoproteins in disease development by Mycobacterium tuberculosis. AB - Glycoproteins play a critical role in host-pathogen interactions, antigenicity, and virulence determination, and are therefore, considered as potential drug targets. The cell wall of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), dominantly contains sugars and lipids. Despite the efforts taken by the World Health Organization to reduce the incidence rate, the prevalence of TB is increasing in certain regions. This is mainly attributed to the emergence of multidrug-resistant bacteria. Factors that contribute to Mtb virulence and antigenicity remain elusive. However, several studies have shown that sugars and lipids are mainly responsible for Mtb pathogenesis and resistance to numerous drugs. This review gives insight into the role of glycoproteins in mycobacterium pathogenesis, disease development, and its implications in drug development. PMID- 22324752 TI - "It's not what you were expecting, but it's still a beautiful journey": the experience of mothers of children with Down syndrome. AB - AIM: The purpose of this study was to describe qualitatively the experience of parenting for mothers of a child with Down syndrome and to explore what if any was the role of spirituality and organized religion in this experience. METHOD: A homogenous sample of eight mothers of children between 7 and 12 years of age with Down syndrome was recruited through a population-based source of families of children with Down syndrome in Western Australia. In-depth interviews were used to explore the mother's experience of parenting and to examine the role of spirituality and organized religion in their personal experience of mothering. RESULTS: In this study, stressful life events recounted by the mothers included initial acceptance, developmental behaviour of the child, functionality of the child, health conditions and financial stress. Overall spirituality was described as a stronger and more dynamic source of support than organized religion in coping with stressors and life's challenges associated with raising a child with Down syndrome. CONCLUSION: Findings from this study revealed that being a mother to a child with Down syndrome can best be described as a mosaic of experiences, emotions and a journey of self growth. Both spirituality and organized religion to a greater or lesser extent were useful in mediating stress and supporting mothers particularly during challenging life events in the course of their journey with their child with Down syndrome. PMID- 22324753 TI - Long-term effects of three multicomponent exercise interventions on physical performance and fall-related psychological outcomes in community-dwelling older adults: a randomized controlled trial. AB - OBJECTIVES: To determine the long-term effects of three strength and balance exercise interventions on physical performance, fall-related psychological outcomes, and falls in older people. DESIGN: A single-blinded, four-group, randomized controlled trial. SETTING: Community, Germany. PARTICIPANTS: Community dwelling adults aged 70 to 90 who had fallen in the past 6 months or reported fear of falling. INTERVENTION: After baseline assessment, 280 participants were randomly assigned to the control group (CG; no intervention; n = 80) or one of three strength and balance exercise interventions (the strength and balance group (SBG; strength and balance only; n = 63), the fitness group (FG; strength and balance plus endurance training; n = 64), or the multifaceted group (MG; strength and balance plus fall risk education; n = 73). The interventions consisted of 32 one-hour group sessions in 16 weeks. MEASUREMENTS: Data on physical performance, fall-related psychological outcomes, and falls were collected for 24 months. RESULTS: Mixed-effects regression analyses showed improved short- and long-term (12 and 24 months, respectively) physical performance for the SBG and FG, particularly regarding mobility, balance, and walking speed (P < .05). The improvements in physical performance outcomes were most prominent in the FG. Fall related psychological outcomes, number of falls, and injurious falls were not significantly different from in the control group. CONCLUSION: Training focusing on strength, balance, and endurance can enhance physical performance for up to 24 months in community-dwelling older adults. These findings did not translate to improved fall-related psychological outcomes or reduced incidence of falls. This demonstrates the need for a different approach (e.g., regarding intervention dose and components) to gain intervention benefits in the multiple domains that contribute to independence and well-being in older adults. PMID- 22324754 TI - Estimation of appendicular muscle mass and fat mass by near infrared spectroscopy in older persons. AB - AIM: Near infrared spectroscopy has been reported to have a high reliability and accuracy in assessing the percentage of body fat. However, whether muscle mass can be accurately estimated using this method has not been established. This study examined whether a near infrared spectroscopy method could estimate appendicular muscle mass and fat mass, with dual-energy X-ray absorptiometry as the standard method for comparison. METHODS: A total of 20 orthopedic inpatients (mean age 73.2 +/- 6.8 years) were recruited for this study. Their body composition was assessed using near infrared spectroscopy and dual-energy X-ray absorptiometry. Appendicular muscle mass and fat mass were estimated from height, weight and optical densities. RESULTS: The optical densities for the upper arm (biceps, triceps) and forearm (flexor carpi radialis) were significantly correlated with appendicular muscle mass (r = 0.534 to 0.623) or fat mass (r = 0.483 to -0.827). Estimated appendicular muscle mass and fat mass explained 89% and 80% of the variance in the dual-energy X-ray absorptiometry-derived muscle mass and fat mass estimates using height, weight and optical density values of the proximal flexor carpi radialis. CONCLUSIONS: Near infrared spectroscopy is a useful method to assess not only fat mass, but also muscle mass in older adults. PMID- 22324756 TI - Facile approach to grafting of poly(2-oxazoline) brushes on macroscopic surfaces and applications thereof. AB - This study reports on a facile and versatile approach for modification of macroscopic surface via grafting of multifunctional poly(2-oxazoline) molecules in brush-like conformation. For this purpose, carboxyl-terminated poly(2 isopropyl-2-oxazoline) molecules have been synthesized by ring-opening cationic polymerization and subsequently grafted on underlined substrates by exploiting the "grafting to" approach. A systematic variation in thickness of the grafted poly (2-isopropyl-2-oxazoline) brushes has been demonstrated. Polymer-modified surfaces have been characterized by means of a number of analytical tools including ellipsometry, X-ray photoelectron spectroscopy, ultraviolate spectroscopy, attenuated total reflection infrared spectroscopy and atomic force microscopy. Interestingly, poly(2-isopropyl-2-oxazoline) molecules have been found to retain their physical properties even after grafting on macroscopic surfaces. Finally, fabricated polymer brushes have been used as platform for stabilization of inorganic nanoparticles on macroscopic surfaces. PMID- 22324757 TI - Environmental performance of algal biofuel technology options. AB - Considerable research and development is underway to produce fuels from microalgae, one of several options being explored for increasing transportation fuel supplies and mitigating greenhouse gas emissions (GHG). This work models life-cycle GHG and on-site freshwater consumption for algal biofuels over a wide technology space, spanning both near- and long-term options. The environmental performance of algal biofuel production can vary considerably and is influenced by engineering, biological, siting, and land-use considerations. We have examined these considerations for open pond systems, to identify variables that have a strong influence on GHG and freshwater consumption. We conclude that algal biofuels can yield GHG reductions relative to fossil and other biobased fuels with the use of appropriate technology options. Further, freshwater consumption for algal biofuels produced using saline pond systems can be comparable to that of petroleum-derived fuels. PMID- 22324755 TI - Housing in environmental complexity following wheel running augments survival of newly generated hippocampal neurons in a rat model of binge alcohol exposure during the third trimester equivalent. AB - BACKGROUND: Binge-like alcohol exposure in neonatal rats during the brain growth spurt causes deficits in adult neurogenesis in the hippocampal dentate gyrus (DG). Previous data from our laboratory demonstrated that 12 days of voluntary wheel running (WR) beginning on postnatal day (PD) 30 significantly increased the number of newly generated cells evident in the DG on PD42 in both alcohol-exposed (AE) and control rats, but 30 days later a sustained beneficial effect of WR was evident only in control rats. This study tested the hypothesis that housing rats in environmental complexity (EC) following WR would promote the survival of the newly generated cells stimulated by WR, particularly in AE rats. METHODS: On PD4 to 9, pups were intubated with alcohol in a binge-like manner (5.25 g/kg/d), sham intubated (SI), or reared normally. In Experiment 1, animals were either assigned to WR during PD30 to 42 or socially housed (SH). On PD42, animals were injected with bromodeoxyuridine (BrdU; 200 mg/kg) and perfused 2 hours later to confirm the WR-induced stimulation of proliferation. In Experiment 2, all animals received WR on PD30 to 42 and were injected with BrdU on the last full day of WR. On PD42, animals were randomly assigned either to EC (WR/EC) or to SH (WR/SH) for 30 days and subsequently perfused and brains were processed for immunohistochemical staining to identify BrdU+-, Ki67+-, and BrdU+/NeuN+-labeled cells in DG. RESULTS: In Experiment 1, WR exposure significantly increased the number of proliferating cells in all 3 postnatal conditions. In Experiment 2, the AE rats given WR/SH had significantly fewer BrdU+ cells compared with control rats given WR/SH. However, WR/EC experience significantly increased the number of surviving BrdU+ cells in both the AE and SI groups compared with WR/SH rats of the same neonatal treatment. Approximately 80% of the surviving BrdU+ cells in the DG across the conditions were colabeled with NeuN. CONCLUSIONS: WR followed by EC could provide a behavioral model for developing interventions in humans to ameliorate hippocampal-dependent impairments associated with fetal alcohol spectrum disorders. PMID- 22324758 TI - Rapid identification of low level glycation sites in recombinant antibodies by isotopic labeling with 13C6-reducing sugars. AB - Recombinant antibodies exhibit low levels of glycation from exposure to reducing sugars during production. As the glycation sites are typically distributed across the entire antibody, the levels at any one site are low and it becomes difficult to detect them in the conventional peptide maps. A model antibody was subjected to forced glycation by incubating with a high concentration of a 1:1 mixture of (12)C(6)/(13)C(6) reducing sugars with the assumption that the same sites in the native antibody will be glycated but to a lower extent. This approach simplified the detection of glycated tryptic peptide elution in the LC/MS analysis by giving a unique signature of two molecular ions with equal intensity and differing by 6.018 Da. An in-house developed script automatically processed large data files to generate a list of such peptide mass pairs. The high mass accuracy of the Orbitrap allowed us to assign the sequences unambiguously by comparison with all possible glycated peptide masses. This sequence list was subsequently used to verify their presence/absence in the digest of the native antibody. This work flow enabled rapid and confident identification of site-specific glycation even when levels are below 0.5%. We found the glycation sites to be distributed across the entire antibody studied. PMID- 22324759 TI - Oxidative stress index may play a key role in patients with pemphigus vulgaris. AB - BACKGROUND: Increased reactive oxygen species (ROS) and lipid peroxidation are seen in many dermatologic disorders, including atopic dermatitis, psoriasis, vitiligo, acne vulgaris, pemphigus vulgaris (PV), lichen planus and alopecia areata. In PV, the increased production of ROS from activated neutrophils reduces the concentrations of antioxidant vitamins and enzymes. OBJECTIVE: The present study aims to determine the oxidative stress index (OSI) by studying serum total oxidant capacity (TOC), lipid hydroperoxide (LOOH) and total antioxidant capacity (TAC) in PV patients. METHODS: The study included 27 PV patients and a control group consisting of 24 healthy volunteers. Serum TOC, LOOH and TAC levels were examined and OSI was measured in the PV patients and the control group. RESULTS: TOC (P = 0.001) and LOOH (P = 0.001) levels as well as OSI (P = 0.001) were found higher in the PV patients, relative to the control group. Serum TAS (P = 0.221) did not differ between groups. Serum TOC, LOOH and TAC levels and OSI in PV patients with mucosal involvement were not different than those in mucocutaneous PV patients. CONCLUSION: Serum TOC and LOOH levels and OSI were higher in the PV patients, in comparison with the control group. Serum TAC level was not different. PMID- 22324761 TI - A validity and reliability study of the Turkish Checklist Individual Strength (CIS) questionnaire in musculoskeletal physical therapy patients. AB - BACKGROUND AND PURPOSE: The aims of this study were the following: (1) to develop a Turkish version of the Checklist Individual Strength Questionnaire (CIS-T); (2) to evaluate the reliability and validity of the CIS-T; and (3) to compare the fatigue levels between musculoskeletal physical therapy patients and healthy subjects. METHODS: The questionnaire was adapted to Turkish using a 'back translation' method. Fifty healthy subjects and 165 musculoskeletal physical therapy patients (128 outpatients and 37 inpatients) were evaluated. To validate the CIS-T, all participants answered both the CIS-T and the Short Form-36 (SF 36). The CIS was re-administered one week later for test-retest reliability. RESULTS: The internal consistency reliability of the CIS-T was Cronbach's alpha = 0.87 and the interclass correlation coefficient reliability was r = 0.92. The item-discriminant validity ranged from r = 0.10 to 0.63. The correlations between the total scores of the scale and the subscale scores of the SF-36 were significant and negative (p < 0.01). The total CIS scores were significantly higher in musculoskeletal physical therapy patients (inpatients) than in healthy subjects, but there was no significant difference between musculoskeletal physical therapy patients (outpatients) and healthy subjects (p < 0.05). CONCLUSION: The CIS-T was a valid and reliable scale for assessing fatigue in physical therapy patients and the fatigue levels of musculoskeletal physical therapy patients were higher than those of healthy subjects. PMID- 22324760 TI - Distribution and properties of the genes encoding the biosynthesis of the bacterial cofactor, pyrroloquinoline quinone. AB - Pyrroloquinoline quinone (PQQ) is a small, redox active molecule that serves as a cofactor for several bacterial dehydrogenases, introducing pathways for carbon utilization that confer a growth advantage. Early studies had implicated a ribosomally translated peptide as the substrate for PQQ production. This study presents a sequence- and structure-based analysis of the components of the pqq operon. We find the necessary components for PQQ production are present in 126 prokaryotes, most of which are Gram-negative and a number of which are pathogens. A total of five gene products, PqqA, PqqB, PqqC, PqqD, and PqqE, are identified as being obligatory for PQQ production. Three of the gene products in the pqq operon, PqqB, PqqC, and PqqE, are members of large protein superfamilies. By combining evolutionary conservation patterns with information from three dimensional structures, we are able to differentiate the gene products involved in PQQ biosynthesis from those with divergent functions. The observed persistence of a conserved gene order within analyzed operons strongly suggests a role for protein-protein interactions in the course of cofactor biosynthesis. These studies propose previously unidentified roles for several of the gene products, as well as identifying possible new targets for antibiotic design and application. PMID- 22324762 TI - Systematic investigation of zinc aminoalkylphosphonates: influence of the alkyl chain lengths on the structure formation. AB - With the high-throughput (HT) methodology, the bifunctional aminoalkylphosphonic acids (AAPA) linker molecules 2-aminoethyl- (AEPA), 3-aminopropyl- (APPA), and 4 aminobutylphosphonic acid (ABPA) [HO(3)P-C(n)H(2n)-NH(2) (n = 2-4)] and zinc nitrate were used to synthesize new metal phosphonates in order to investigate the influence of the alkyl chain length on the structure formation. The systematic investigations led to one known (ZnO(3)PC(2)H(4)NH(2)) and six new compounds: one using AEPA, three using APPA, and two using ABPA. The crystal structures of five compounds were determined by single crystal X-ray diffraction, using X-ray powder diffraction (XRPD) data as well as structure modeling employing force field methods. For compound 1, Zn(O(3)P-C(2)H(4) NH(3))(NO(3))(H(2)O) (monoclinic, Cc, a = 4.799(1) A, b = 29.342(6) A, c = 5.631(1) A, beta = 91.59(3) degrees , V = 792.7(3) A(3), Z = 4), and compound 2, Zn(2)(OH)(O(3)P-C(3)H(6)-NH(3))(NO(3)) (monoclinic, P2/c, a = 12.158(2) A, b = 5.0315(10) A, c = 13.952(3) A, beta = 113.23(3) degrees , V = 784.3(3) A(3), Z = 2), the structures were determined using single crystal X-ray diffraction data. The crystal structures of [Zn(O(3)P-C(3)H(6)-NH(2))].H(2)O (3) (monoclinic, P2(1)/c, a = 9.094(2) A, b = 5.0118(7) A, c = 16.067(4) A, beta = 90.38(2) degrees , V = 732.3(2) A(3), Z = 4) and Zn(O(3)P-C(4)H(8)-NH(2)) (5) (monoclinic, P2(1)/c, a = 8.570(7) A, b = 8.378(4) A, c = 9.902(6) A, beta = 90.94(5) degrees , V = 710.9(8) A(3), Z = 4) were determined using XRPD data. The structural model for compound 6, Zn(O(3)P-C(4)H(8)-NH(3))(NO(3))(H(2)O), was established using lattice parameters from XRPD data and following crystal structure modeling employing force field methods. The structures depend strongly on the alkyl chain length n. For n = 2 and 4 isoreticular compounds are observed, while n = 3 leads to new structures. Larger amounts of all compounds were obtained employing scale up syntheses in a conventional oven as well as in a microwave reactor system. In addition, in situ energy dispersive X-ray diffraction (EDXRD) experiments at 130 degrees C were performed at beamline F3 at HASYLAB, DESY, Hamburg, to investigate the formation of compounds 2 and 3 as well as the phase transformation of 2 into 3 upon addition of NaOH. All compounds were characterized in detail using X-ray powder diffraction, IR/Raman spectroscopy, and thermogravimetric and elemental analysis. PMID- 22324763 TI - Intermolecular hydroacylation: high activity rhodium catalysts containing small bite-angle diphosphine ligands. AB - Readily prepared and bench-stable rhodium complexes containing methylene bridged diphosphine ligands, viz. [Rh(C(6)H(5)F)(R(2)PCH(2)PR'(2))][BAr(F)(4)] (R, R' = (t)Bu or Cy; Ar(F) = C(6)H(3)-3,5-(CF(3))(2)), are shown to be practical and very efficient precatalysts for the intermolecular hydroacylation of a wide variety of unactivated alkenes and alkynes with beta-S-substituted aldehydes. Intermediate acyl hydride complexes [Rh((t)Bu(2)PCH(2)P(t)Bu(2))H{kappa(2)(S,C) SMe(C(6)H(4)CO)}(L)](+) (L = acetone, MeCN, [NCCH(2)BF(3)](-)) and the decarbonylation product [Rh((t)Bu(2)PCH(2)P(t)Bu(2))(CO)(SMePh)](+) have been characterized in solution and by X-ray crystallography from stoichiometric reactions employing 2-(methylthio)benzaldehdye. Analogous complexes with the phosphine 2-(diphenylphosphino)benzaldehyde are also reported. Studies indicate that through judicious choice of solvent and catalyst/substrate concentration, both decarbonylation and productive hydroacylation can be tuned to such an extent that very low catalyst loadings (0.1 mol %) and turnover frequencies of greater than 300 h(-1) can be achieved. The mechanism of catalysis has been further probed by KIE and deuterium labeling experiments. Combined with the stoichiometric studies, a mechanism is proposed in which both oxidative addition of the aldehyde to give an acyl hydride and insertion of the hydride into the alkene are reversible, with the latter occurring to give both linear and branched alkyl intermediates, although reductive elimination for the linear isomer is suggested to have a considerably lower barrier. PMID- 22324764 TI - Metabolite profile shifts in the heathland lichen Cladonia portentosa in response to N deposition reveal novel biomarkers. AB - The heathland lichen Cladonia portentosa was collected from sites in mainland Britain differing either in rates of wet N deposition or in annual mean N concentration in rainfall based on a modelled data set. Methanolic extracts of thalli were analyzed by liquid chromatography time-of-flight mass spectrometry to yield metabolic profiles. Differences between sites in metabolite concentration were quantified using multivariate statistical tools and used to identify potential biomarker molecules. The abundances of three structurally related betaine lipids showed an increase with increasing modelled N deposition to a threshold of 22.3 kg ha(-1) year(-1) after which they remained constant. In contrast, the abundance of a phosphatidylcholine (PC) lipid showed concomitant decrease. Correlations of the identified biomarkers with N deposition and precipitation were stronger than those with N concentrations. The results presented in this study clearly show that N enrichment associated with tissue P limitation changes lipid composition, leading to shifts from PCs to betaine lipids, and that these lipids identified have the potential to be used as biomarkers for nitrogen enrichment. PMID- 22324766 TI - Improving accuracy of adolescents' substance use reports via text messaging. PMID- 22324768 TI - Anisotropy on the collective dynamics of water confined in swelling clay minerals. AB - Collective excitations of water confined in the interlayer space of swelling clay minerals were studied by means of inelastic neutron scattering. The effect of bidimensional confinement on the dynamics of the interlayer water was investigated by using a synthetic Na-saponite sample with a general formula of Si(7.3)Al(0.7)Mg(6)O(20)(OH)(4)Na(0.7) in a bilayer hydration state. Experimental results reveal two inelastic signals, different from those described for bulk water with a clear anisotropy on the low-energy excitation of the collective dynamics of interlayer water, this difference being stronger in the perpendicular direction. Results obtained for the parallel direction follow the same trend as bulk water, and the effect of the confinement is mainly manifested from the fact that clay interlayer water is more structured than bulk water. Data obtained in the perpendicular direction display a nondispersive behavior below a cutoff wavenumber value, Q(c), indicating a nonpropagative excitation below that value. Molecular dynamics simulations results agree qualitatively with the experimental results. PMID- 22324769 TI - Structure and elasticity of lipid membranes with genistein and daidzein bioflavinoids using X-ray scattering and MD simulations. AB - This work reports the effects of the bioflavinoids genistein and daidzein on lipid bilayers as determined by volume measurements, X-ray scattering, and molecular dynamics simulations. The experimental and simulated total molecular volumes were found to be in outstanding agreement with each other before the addition of genistein and daidzein and also after their addition. Both bioflavinoids inserted into the hydrocarbon region of both DOPC and diphytanoylPC near the carbonyls of the lipids and both decreased the bilayer thicknesses. The long axes of both bioflavinoids were oriented nearly parallel to the plane of the bilayer with their carbonyl groups preferentially pointed toward the proximal surface. A difference is that daidzein had a solubility limit of ~0.14 mol fraction in DOPC (~0.12 mol fraction in diphytanoylPC), whereas genistein was soluble at least to 0.20 mol fraction in both lipid membranes. Measurements of bending modulus K(C) and simulation results for area compressibility modulus K(A) indicate that both bioflavinoids soften bilayers. PMID- 22324770 TI - Fitness of macrolide resistant Campylobacter coli and Campylobacter jejuni. AB - The aim of this study was to investigate the fitness of macrolide resistant Campylobacter coli and Campylobacter jejuni. The in vitro growth, the survival on food matrix, and the in vivo colonization of C. jejuni and C. coli susceptible isolates and their isogenic resistant mutants were studied. In vitro experiments demonstrated that macrolide resistance imposed a fitness cost when the susceptible strains and their isogenic resistant mutants were cultured in competition. When inoculated in food matrix, the resistant C. jejuni mutant was no longer detectable after 3 to 5 days but the susceptible strain remained detectable for over 18 days. No difference in survival in food matrix was observed between susceptible and resistant C. coli. When inoculated in vivo in chickens, the macrolide susceptible and resistant C. coli displayed similar levels of colonization, both in separated inoculations and during competitive assays. Strikingly, when mono-inoculated or co-inoculated into chickens, macrolide susceptible C. jejuni outcompeted the macrolide resistant population. However, a spontaneous mutant that evolved in vivo showed a colonization capacity similar to the susceptible strain. Our findings demonstrate the effect of macrolide resistance on the fitness of Campylobacter but suggest that evolved mutants may be as fit as susceptible strains. PMID- 22324771 TI - Metabolic biomarkers of prenatal alcohol exposure in human embryonic stem cell derived neural lineages. AB - BACKGROUND: Fetal alcohol spectrum disorders (FASD) are a leading cause of neurodevelopmental disability. The mechanisms underlying FASD are incompletely understood, and biomarkers to identify those at risk are lacking. Here, we perform metabolomic analysis of embryoid bodies and neural lineages derived from human embryonic stem (hES) cells to identify the neural secretome produced in response to ethanol (EtOH) exposure. METHODS: WA01 and WA09 hES cells were differentiated into embryoid bodies, neural progenitors, or neurons. Cells along this progression were cultured for 4 days with 0, 0.1, or 0.3% EtOH. Supernatants were subjected to C18 chromatography followed by ESI-QTOF-MS. Features were annotated using public databases, and the identities of 4 putative biomarkers were confirmed with purified standards and comparative MS/MS. RESULTS: EtOH treatment induced statistically significant changes to metabolite abundance in human embryoid bodies (180 features), neural progenitors (76 features), and neurons (42 features). There were no shared significant features between different cell types. Fifteen features showed a dose-response to EtOH. Four chemical identities were confirmed: L-thyroxine, 5'-methylthioadenosine, and the tryptophan metabolites, L-kynurenine and indoleacetaldehyde. One feature with a putative annotation of succinyladenosine was significantly increased in both EtOH treatments. Additional features were selective to EtOH treatment but were not annotated in public databases. CONCLUSIONS: EtOH exposure induces statistically significant changes to the metabolome profile of human embryoid bodies, neural progenitors, and neurons. Several of these metabolites are normally present in human serum, suggesting their usefulness as potential serum FASD biomarkers. These findings suggest the biochemical pathways that are affected by EtOH in the developing nervous system and delineate mechanisms of alcohol injury during human development. PMID- 22324772 TI - A single LipiFlow(r) Thermal Pulsation System treatment improves meibomian gland function and reduces dry eye symptoms for 9 months. AB - PURPOSE: To evaluate the effect of a single treatment with the LipiFlow((r)) Thermal Pulsation System on signs of meibomian gland dysfunction (MGD) and dry eye symptoms over a 9-month period. METHODS: Patients (n = 42 eyes, 21 subjects) diagnosed with MGD and dry eye symptoms were recruited for a non-significant risk, prospective, open-label, 1-month clinical trial. Patients received a single 12-minute treatment using the LipiFlow((r)) Thermal Pulsation System on each eye. The LipiFlow((r)) device applies heat to the conjunctival surfaces of the upper and lower inner eyelids while simultaneously applying pulsatile pressure to the outer eyelid surfaces to express the meibomian glands. Patient symptoms were evaluated using the Ocular Surface Disease Index (OSDI) and Standard Patient Evaluation for Eye Dryness (SPEED) dry eye questionnaires; tear break-up time was measured with the dry eye test (DETTM); and meibomian gland function was evaluated using a standardized diagnostic expression technique. Data are presented for patient's pre-treatment (baseline) and at 1-month and 9-month post treatment. RESULTS: Meibomian gland secretion scores improved significantly from baseline (4.4 +/- 4.0) to 1-month post-treatment (11.3 +/- 6.2; p < 0.0001) and this improvement was maintained with no significant regression at 9 months (11.7 +/- 5.9). Similarly, baseline tear break-up time (4.8 +/- 3.2) was significantly increased at 1 month (9.6 +/- 7.6; p < 0.001) and this increase was maintained with no significant regression at 9 months (7.1 +/- 5.6). Symptom scores on both OSDI and SPEED questionnaires improved significantly at 1 month (p < 0.0001) and this improvement was maintained at 9 months. CONCLUSION: With such prolonged improvement in signs and symptoms of dry eye disease, the LipiFlow((r)) Thermal Pulsation System offers a technological advancement for the treatment of dry eye disease secondary to meibomian gland dysfunction. A single 12-minute LipiFlow((r)) treatment results in up to 9 months of sustained improvement of meibomian gland function, tear break-up time and dry eye symptoms that are unparalleled with current dry eye treatments. PMID- 22324774 TI - Fresh green tea and gallic acid ameliorate oxidative stress in kainic acid induced status epilepticus. AB - Green tea is one of the most-consumed beverages due to its taste and antioxidative polyphenols. However, the protective effects of green tea and its constituent, gallic acid (GA), against kainic acid (KA)-induced seizure have not been studied. We investigated the effect of fresh green tea leaf (GTL) and GA on KA-induced neuronal injury in vivo and in vitro. The results showed that GTL and GA reduced the maximal seizure classes, predominant behavioral seizure patterns, and lipid peroxidation in male FVB mice with status epilepticus (SE). GTL extract and GA provided effective protection against KA-stressed PC12 cells in a dose dependent manner. In the protective mechanism study, GTL and GA decreased Ca(2+) release, ROS, and lipid peroxidation from KA-stressed PC12 cells. Western blot results revealed that mitogen-activated protein kinases (MAPKs), RhoA, and COX-2 expression were increased in PC12 cells under KA stress, and expression of COX-2 and p38 MAPK, but not RhoA, was significantly reduced by GTL and GA. Furthermore, GTL and GA were able to reduce PGE(2) production from KA-stressed PC12 cells. Taken together, the results showed that GTL and GA provided neuroprotective effects against excitotoxins and may have a clinical application in epilepsy. PMID- 22324773 TI - Three scales assessing high school students' attitudes and perceived norms about seeking adult help for distress and suicide concerns. AB - Validated measures that can be administered to school populations are needed to advance knowledge of help-seeking processes and to evaluate suicide prevention programs that target help-seeking. With 6,370 students from 22 high schools, we assessed the psychometric properties of three brief measures: Help-Seeking Acceptability at School, Adult Help for Suicidal Youth, and Reject Codes of Silence. Internal consistency coefficients ranged from .64 to .84. In support of construct validity, lower scores on each scale were associated with more maladaptive coping norms; for each one unit increase on each scale, students were one third to one half as likely to report suicidal ideation, suicide attempts, and elevated depression. PMID- 22324775 TI - Unquestioned answers or unanswered questions: beliefs about science guide responses to uncertainty in climate change risk communication. AB - In two experimental studies we investigated the effect of beliefs about the nature and purpose of science (classical vs. Kuhnian models of science) on responses to uncertainty in scientific messages about climate change risk. The results revealed a significant interaction between both measured (Study 1) and manipulated (Study 2) beliefs about science and the level of communicated uncertainty on willingness to act in line with the message. Specifically, messages that communicated high uncertainty were more persuasive for participants who shared an understanding of science as debate than for those who believed that science is a search for absolute truth. In addition, participants who had a concept of science as debate were more motivated by higher (rather than lower) uncertainty in climate change messages. The results suggest that achieving alignment between the general public's beliefs about science and the style of the scientific messages is crucial for successful risk communication in science. Accordingly, rather than uncertainty always undermining the effectiveness of science communication, uncertainty can enhance message effects when it fits the audience's understanding of what science is. PMID- 22324776 TI - Quantification of prothrombin in human plasma amplified by autocatalytic reaction. AB - By site directed mutagenesis, we have produced recombinant mutants of human and mouse prethrombin-2 which are able to convert themselves autocatalytically into alpha-thrombin. We also have created a new method to amplify the signal of bioanalytical assays based on the autocatalytic activation of these mutated proenzymes. The activation of the mutants by active alpha-thrombin triggers an autocatalytic reaction which leads to more active thrombin resulting in the amplification of the readout signal. Addition of mutated mouse prethrombin-2 into the conventional assay for prothrombin level in human plasma, employing ecarin and the fluorogenic substrate, resulted in improvement of the detection limit by 2 orders of magnitude. PMID- 22324778 TI - Stem-forming regions that are essential for the amyloidogenesis of prion proteins. AB - Prion diseases represent fatal neurodegenerative disorders caused by the aggregation of prion proteins. With regard to the formation of the amyloidogenic cross-beta-structure, the initial mechanism in the conversion to a beta-structure is critically important. To explore the core regions forming a stem of the amyloid, we designed and prepared a series of peptides comprised of two native sequences linked by a turn-inducing dipeptide moiety and examined their ability to produce amyloids. A sequence alignment of the peptides bearing the ability to form amyloid structures revealed that paired strands consisting of VNITI (residues 180-184) and VTTTT (residues 189-193) are the core regions responsible for initiating the formation of cross-beta-structures and for further ordered aggregation. In addition, most of the causative mutations responsible for inherited prion diseases were found to be located in these stem-forming regions on helix H2 and their counterpart on helix H3. Moreover, the volume effect of the nonstem domain, which contains ~200 residues, was deduced to be a determinant of the nature of the association such as oligomerization, because the stem-forming domain is only a small part of a prion protein. Taken together, we conclude that the mechanism underlying the initial stage of amyloidogenesis is the exposure of a newly formed intramolecular beta-sheet to a solvent through the partial transition of a native structure from an alpha-helix to a beta-structure. Our results also demonstrate that prion diseases caused by major prion proteins except the prions of some fungi such as yeast are inherent only in mammals, as evidenced by a comparison of the corresponding sequences to the stem-forming regions among different animals. PMID- 22324777 TI - Mass discharge in a tracer plume: evaluation of the Theissen Polygon Method. AB - A tracer plume was created within a thin aquifer by injection for 299 d of two adjacent "sub-plumes" to represent one type of plume heterogeneity encountered in practice. The plume was monitored by snapshot sampling of transects of fully screened wells. The mass injection rate and total mass injected were known. Using all wells in each transect (0.77 m well spacing, 1.4 points/m(2) sampling density), the Theissen Polygon Method (TPM) yielded apparently accurate mass discharge (M(d) ) estimates at three transects for 12 snapshots. When applied to hypothetical sparser transects using subsets of the wells with average spacing and sampling density from 1.55 to 5.39 m and 0.70 to 0.20 points/m(2) , respectively, the TPM accuracy depended on well spacing and location of the wells in the hypothesized transect with respect to the sub-plumes. Potential error was relatively low when the well spacing was less than the widths of the sub-plumes (>0.35 points/m(2) ). Potential error increased for well spacing similar to or greater than the sub-plume widths, or when less than 1% of the plume area was sampled. For low density sampling of laterally heterogeneous plumes, small changes in groundwater flow direction can lead to wide fluctuations in M(d) estimates by the TPM. However, sampling conducted when flow is known or likely to be in a preferred direction can potentially allow more useful comparisons of M(d) over multiyear time frames, such as required for performance evaluation of natural attenuation or engineered remediation systems. PMID- 22324779 TI - Environmental, biochemical and genetic drivers of DMSP degradation and DMS production in the Sargasso Sea. AB - Dimethylsulfide (DMS) is a climatically relevant trace gas produced and cycled by the surface ocean food web. Mechanisms driving intraannual variability in DMS production and dimethylsulfoniopropionate (DMSP) degradation in open-ocean, oligotrophic regions were investigated during a 10-month time-series at the Bermuda Atlantic Time-series Study site in the Sargasso Sea. Abundance and transcription of bacterial DMSP degradation genes, DMSP lyase enzyme activity, and DMS and DMSP concentrations, consumption rates and production rates were quantified over time and depth. This interdisciplinary data set was used to test current hypotheses of the role of light and carbon supply in regulating upper ocean sulfur cycling. Findings supported UV-A-dependent phytoplankton DMS production. Bacterial DMSP degraders may also contribute significantly to DMS production when temperatures are elevated and UV-A dose is moderate, but may favour DMSP demethylation under low UV-A doses. Three groups of bacterial DMSP degraders with distinct intraannual variability were identified and niche differentiation was indicated. The combination of genetic and biochemical data suggest a modified 'bacterial switch' hypothesis where the prevalence of different bacterial DMSP degradation pathways is regulated by a complex set of factors including carbon supply, temperature and UV-A dose. PMID- 22324780 TI - Three-terminal graphene negative differential resistance devices. AB - A new mechanism for negative differential resistance (NDR) is discovered in three terminal graphene devices based on a field-effect transistor configuration. This NDR effect is a universal phenomenon for graphene and is demonstrated in devices fabricated with different types of graphene materials and gate dielectrics. Operation of conventional NDR devices is usually based on quantum tunneling or intervalley carrier transfer, whereas the NDR behavior observed here is unique to the ambipolar behavior of zero-bandgap graphene and is associated with the competition between electron and hole conduction as the drain bias increases. These three terminal graphene NDR devices offer more operation flexibility than conventional two-terminal devices based on tunnel diodes, Gunn diodes, or molecular devices, and open up new opportunities for graphene in microwave to terahertz applications. PMID- 22324781 TI - Focal contact formation of vascular smooth muscle cells on Langmuir-Blodgett and solvent-cast films of biodegradable poly(ester amide)s. AB - The ability of biomaterials to support the adhesion of cells is a necessary condition for their use in scaffold-guided tissue engineering. Waveguide evanescent field fluorescence (WEFF) microscopy is a relatively new microscopic technique that allows the number of cell adhesions to a waveguide surface be measured by imaging the interfacial contact region between the cells and their substratum. In this work, the adhesion of human coronary artery smooth muscle cells (HCASMCs) to ultrathin films (20 nm) of poly(ester amide)s (PEAs) prepared by Langmuir-Blodgett (LB) technology on waveguides was investigated and compared with conventional vinculin immunostaining on solvent cast PEA films. Cell culture was conducted both in the presence and absence of serum to evaluate the effect of nonspecific protein adsorption that mediates cell adhesion. WEFF microscopy analyses revealed that the cationic PEA enhanced the number of attachment sites compared with the control waveguides regardless of the culture medium. Although differences in cell adhesions between different PEAs were suggested by the results, no statistically significant differences were found. Similar results were observed with presently and previously reported vinculin immunostaining studies, further validating the use of WEFF microscopy to quantify cell adhesions. Moreover, the focal adhesions of the HCASMCs to the PEA surfaces indicate these PEAs can promote integrin signaling, which is vital in cell survival, migration, and proliferation, and ultimately in scaffold-guided vascular tissue engineering. PMID- 22324783 TI - Reflectance confocal microscopy in the diagnosis of partially and completely amelanotic melanoma: report on seven cases. AB - BACKGROUND: The clinical diagnosis of amelanotic melanoma is often challenging, because the classical clinical and dermoscopic features of pigmented melanoma are usually missing. The reflectance confocal microscopy (RCM) offers an additional possibility of an in vivo diagnosis of both pigmented and amelanotic melanoma lesions. OBJECTIVES: To test the value of RCM in vivo in the preoperative prediction of melanoma lesions lacking significant pigment and to compare the results with the evaluation by dermoscopy and histopathology. METHODS: We examined seven patients with the clinically uncertain differential diagnosis of partially or completely amelanotic melanoma by RCM and dermoscopy prior to surgical excision of the lesions according to the previously suggested dermoscopy algorithm and RCM score for melanoma. The following RCM features were evaluated: major criteria scored +2 (non-edged papillae, cytological atypia at the dermo epidermal junction) and minor criteria +1 (roundish pagetoid cells, widespread pagetoid infiltration, nucleated cells within dermal papillae, cerebriform cell clusters). The dermoscopic evaluation included the following criteria: polymorphous vessels, dotted and linear irregular vessels, hairpin vessels, pink erythematous colour, milky red areas, irregularly shaped depigmentation, blue grey dots and subtle pigmentation. RESULTS: The preoperative in vivo RCM analysis revealed common features of melanoma also found in pigmented melanoma lesions. All lesions showed a score above three in the applied RCM algorithm which was proposed earlier as the threshold for malignancy. In dermoscopy, five of seven lesions showed characteristic vascular changes. CONCLUSION: In vivo RCM is a valuable tool in the preoperative diagnosis of partially and completely amelanotic tumours suspicious for melanoma in addition to dermoscopic evaluation. PMID- 22324784 TI - Rhenium(V) and technetium(V) nitrido complexes with mixed tridentate pi-donor and monodentate pi-acceptor ligands. AB - Mixed-ligand [M(N)(SNS)(PPh(3))] complexes (M = Tc, Re) (1, 2) were prepared by reaction of the precursor [M(N)Cl(2)(PPh(3))(2)] with ligand 2,2' dimercaptodiethylamine [H(2)SNS = NH(CH(2)CH(2)SH)(2)] in refluxing dichloromethane/ethanol mixtures. In these compounds, 2,2'-dimercaptodiethylamine acts as a dianionic tridentate chelating ligand bound to the [M=N](2+) group through the two pi-donor deprotonated sulfur atoms and the protonated amine nitrogen atom. Triphenylphosphine completes the coordination sphere, acting as a monodentate ligand. [M(N)(NS(2))(PPh(3))] complexes can assume two different isomeric forms depending on the syn and anti orientations of the hydrogen atom bound to the central nitrogen atom of the SNS ligand with respect to the M=N moiety. X-ray crystallography of the syn isomer of complex 2 demonstrated that it has a distorted trigonal bipyramidal geometry with the nitrido group and the two sulfur atoms defining the equatorial plane, the phosphorus atom of the monophosphine and the protonated amine nitrogen of the tridentate ligand spanning the two reciprocal trans positions along the axis perpendicular to the trigonal plane. Synthesis of the analogous Tc derivatives with tris(2 cyanoethyl)phosphine, [Tc(N)(SNS)(PCN)] [(PCN = P(CH(2)CH(2)CN)(3)], required the preliminary preparation of the new precursor [Tc(N)(PCN)(2)Cl(2)](2) (3), which was prepared by reacting [n-NBu(4)][Tc(N)Cl(4)] with a high excess of PCN. The crystal structure of compound 3 consists of a noncrystallographic centrosymmetric dimer of Tc(V) nitrido complexes having an octahedral geometry. In this arrangement, the apical positions are occupied by two tris(2-cyanoethyl)phosphine groups and the equatorial positions by the nitrido group whereas the two Cl(-) anions and one cyano ligand belong to the other octahedral component of the dimer. By reacting the new precursor [Tc(N)(PCN)(2)Cl(2)](2) with the ligand H(2)SNS the complex [Tc(N)(SNS)(PCN)] (5) was finally obtained in acetonitrile solution. The new Tc(III) complex trans-[Tc(PCN)(2)Cl(4)][n-NBu(4)] (4) was also isolated from the reaction solution used for preparing complex 3 as side product and characterized by X-ray diffraction. The crystal structure of 4 consists of independent trans-[TcCl(4)(PCN)(2)](-) anions situated on crystallographic centers of symmetry and tetrabutylammonium cations in general positions. PMID- 22324785 TI - Pulmonary events in antiphospholipid syndrome: influence of antiphospholipid antibody type and levels. AB - OBJECTIVE: This prospective clinical study examined the association between subclasses of antiphospholipid antibodies (aPL) and pulmonary manifestations in antiphospholipid syndrome (APS). METHODS: The cohort involved 329 patients: 214 patients with primary APS (PAPS) and 115 patients with secondary APS (SAPS). aPL analysis included detection of serum anticardiolipin antibodies [aCL (IgG/IgM)], beta2 glycoprotein I [beta2GPI (IgG/IgM)], and lupus anticoagulant (LA). RESULTS: In SAPS, high aCL IgG levels (> 100 PLU/mL) were more common in major pulmonary arterial thrombosis (p = 0.006) and medium aCL IgG levels (41-99 PLU/mL) in adult respiratory distress syndrome (ARDS; p = 0.047) and fibrosing alveolitis (p = 0.002). aCL IgG antibodies were more common in SAPS (p = 0.037). In PAPS, fibrosing alveolitis was more common in patients with medium beta2GPI IgM levels (p = 0.0001). LA correlated with pulmonary embolism (p = 0.03) and microthrombosis (p = 0.03) in SAPS, and with pulmonary microthrombosis (p = 0.03) in PAPS. Males were more likely to develop secondary pulmonary hypertension when diagnosed with PAPS (p = 0.019). CONCLUSION: Certain classes of aPL are associated with distinct pulmonary manifestation, indicating their predictive role and importance in diagnosis and treatment of APS. PMID- 22324786 TI - Intermolecular interactions in complex liquids: effective fragment potential investigation of water-tert-butanol mixtures. AB - Structure and bonding patterns in tert-butanol (TBA)-water mixtures are investigated by using molecular dynamics simulations with the effective fragment potential (EFP) method. EFP is a model potential in which all parameters are obtained from a set of ab initio calculations on isolated fragment molecules. Mixed-basis EFP potentials (called "EFPm") for water and TBA molecules were prepared and tested in this work. The accuracy of these EFP potentials is justified by comparison of structures and binding energies in water, TBA, and water-TBA dimers with MP2/6-311++G(d,p) data. It has been found that the discrepancies between EFP and MP2 do not exceed 0.1 A in intermolecular distances and 1 kcal/mol in binding energies. Structures of TBA-water solutions with 0.0, 0.06, 0.11, 0.16, and 0.50 TBA mole fractions were analyzed by using radial distribution functions (RDFs) and coordination numbers. These results suggest that, at low TBA concentrations, the structure of water is enhanced and water and TBA are not homogeneously mixed at the molecular level. In the equimolar TBA water solution, the microscopic mixing is more complete. Analysis of the energy components in TBA-water solutions shows that, while the electrostatic and exchange-repulsion terms provide the largest contributions to the total potential energy, the relative importance of the polarization and dispersion terms depends on the concentration of TBA. With an increase of TBA concentration, the fraction of the dispersion energy increases, while the fraction of polarization energy diminishes. However, both polarization and dispersion terms are essential for accurate description of these systems. PMID- 22324788 TI - Probing the 5f orbital contribution to the bonding in a U(V) ketimide complex. AB - Reaction of UCl(4) with 5 equiv of Li(N?C(t)BuPh) generates the homoleptic U(IV) ketimide complex [Li(THF)(2)][U(N?C(t)BuPh)(5)] (1) in 71% yield. Similarly, reaction of UCl(4) with 5 equiv of Li(N?C(t)Bu(2)) affords [Li(THF)][U(N?C(t)Bu(2))(5)] (2) in 67% yield. Oxidation of 2 with 0.5 equiv of I(2) results in the formation of the neutral U(V) complex U(N?C(t)Bu(2))(5) (3). In contrast, oxidation of 1 with 0.5 equiv of I(2), followed by addition of 1 equiv of Li(N?C(t)BuPh), generates the octahedral U(V) ketimide complex [Li][U(N?C(t)BuPh)(6)] (4) in 68% yield. Complex 4 can be further oxidized to the U(VI) ketimide complex U(N?C(t)BuPh)(6) (5). Complexes 1-5 were characterized by X-ray crystallography, while SQUID magnetometry, EPR spectroscopy, and UV-vis-NIR spectroscopy measurements were also preformed on complex 4. Using this data, the crystal field splitting parameters of the f orbitals were determined, allowing us to estimate the amount of f orbital participation in the bonding of 4. PMID- 22324789 TI - Synthesis and photophysical properties of aryl-substituted 2-borylbenzaldimines and their extended pi-conjugated congeners. AB - Novel N-aryl-substituted 2-borylbenzaldimines 6 and related systems with extended pi-framework 7 based on two borylbenzaldimine units linked by a spacer moiety were synthesized by condensation reactions of 2-(dimesitylboryl)benzaldehyde 3 with various amines 4 and diamines 5. All compounds were completely characterized including X-ray diffraction, especially in view of Lewis acid-base B-O and B-N interactions. The electronic as well as the photophysical properties of bisimines 7 were determined using cyclic voltammetry, UV/vis, and fluorescence spectroscopy and quantum chemistry. These compounds feature large Stokes shifts and reversible reduction waves. Interestingly, UV irradiation experiments unfold enhanced photostability for compounds 7 with an extended pi-skeleton. By use of 1,8 diaminonaphthalene we observed the formation of a hitherto unknown BN heterocyclic compound 9 fused with a perimidine skeleton. Structural and energetic aspects were evaluated by high level quantum chemical methods (DFT and SCS-MP2-calculations). PMID- 22324790 TI - Study of ion specific interactions of alkali cations with dicarboxylate dianions. AB - Alkali metal cations often show pronounced ion-specific interactions and selectivity with macromolecules in biological processes, colloids, and interfacial sciences, but a fundamental understanding about the underlying microscopic mechanism is still very limited. Here we report a direct probe of interactions between alkali metal cations (M(+)) and dicarboxylate dianions, ( )O(2)C(CH(2))(n)CO(2)(-) (D(n)(2-)) in the gas phase by combined photoelectron spectroscopy (PES) and ab initio electronic structure calculations on nine M(+) D(n)(2-) complexes (M = Li, Na, K; n = 2, 4, 6). PES spectra show that the electron binding energy (EBE) decreases from Li(+) to Na(+) to K(+) for complexes of M(+)-D(2)(2-), whereas the order is Li(+) < Na(+) ~ K(+) when M(+) interacts with a more flexible D(6)(2-) dianion. Theoretical modeling suggests that M(+) prefers to interact with both ends of the carboxylate -COO(-) groups by bending the flexible aliphatic backbone, and the local binding environments are found to depend upon backbone length n, carboxylate orientation, and the specific cation M(+). The observed variance of EBEs reflects how well each specific dicarboxylate dianion accommodates each M(+). This work demonstrates the delicate interplay among several factors (electrostatic interaction, size matching, and strain energy) that play critical roles in determining the structures and energetics of gaseous clusters as well as ion specificity and selectivity in solutions and biological systems. PMID- 22324791 TI - Waist circumference and metabolic syndrome: the risk for silent coronary artery disease in males. AB - BACKGROUND: Waist circumference (WC) is a component used to define metabolic syndrome. However, its role as an independent predictor of silent coronary artery disease (CAD), above its contribution to metabolic syndrome, remains unknown. METHODS: Male veterans without known CAD, undergoing cardiac stress testing for indications other than typical angina or its equivalent, were evaluated for the presence of silent CAD. High WC and metabolic syndrome were defined per the revised National Cholesterol Education Program (NCEP-R) and the International Diabetes Federation (IDF) criteria. RESULTS: Data on 1,071 patients (age 61+/-11 years) were analyzed retrospectively. On multivariable logistic regression analysis [odds ratio (OR), 95% confidence interval (CI), P value), a WC >=94 cm (1.42, 1.04-1.93; P=0.026), metabolic syndrome by NCEP-R (1.73, 1.29-2.33; P<0.0001), and metabolic syndrome by IDF (1.57, 1.17-2.11; P=0.003) were independent predictors of silent CAD. When comparing patients meeting criteria for metabolic syndrome defined by either NCEP-R or IDF, the prevalence of silent CAD was not statistically different (P=0.86). The prevalence of silent CAD associated with a high WC was not inferior to that seen between silent CAD and metabolic syndrome as defined by either criterion. Last, among patients with metabolic syndrome defined by NCEP-R, those with a high WC as a defining component of metabolic syndrome had a higher prevalence of silent CAD (30% vs. 20%; P=0.026). CONCLUSION: A WC >=94 cm in males is independently associated with an increased prevalence of silent CAD. In patients with metabolic syndrome, this prevalence is increased by the presence of high WC. PMID- 22324792 TI - Prediction of cardiovascular events with consideration of general and central obesity measures in diabetic adults: results of the 8.4-year follow-up. AB - BACKGROUND: Obesity is one of the most important cardiovascular disease (CVD) risk factors among diabetic populations. We evaluated the ability of different anthropometric measures for predicting CVD among type 2 diabetic patients. METHODS: The study consisted of 411 men and 599 women, aged >=30 years, free of CVD at baseline with a median follow-up of 8.4 years. The adjusted hazard ratios (HRs) for CVD were calculated for a 1 standard deviation change in body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to height ratio (WHtR) using Cox proportional regression analysis. RESULTS: A total of 188 CVD events occurred (men, 90; women, 98). In women, in confounder-adjusted analysis [age, fasting plasma glucose (instead of glycosylated hemoglobin), and positive family history of CVD], WHR was associated with incident CVD [1.32 (1.06 1.65)], followed by WC and WHtR, which were marginally significant (P=0.06 and 0.08, respectively); after adjustment for hypertension and hypercholesterolemia, only WHR predicted CVD significantly. In men, the confounder-adjusted (age, fasting plasma glucose, and aspirin use) HR to predict CVD was significant only for WHR [HR 1.21(1.00-1.48)]. CONCLUSION: This study showed WHR was the most powerful predictor of CVD among anthropometric measures, followed by WHtR, in diabetic population. PMID- 22324793 TI - Alcohol does not increase slow wave sleep. PMID- 22324794 TI - Inhibitory effects of gossypol, gossypolone, and apogossypolone on a collection of economically important filamentous fungi. AB - Racemic gossypol and its related derivatives gossypolone and apogossypolone demonstrated significant growth inhibition against a diverse collection of filamentous fungi that included Aspergillus flavus, Aspergillus parasiticus, Aspergillus alliaceus, Aspergillus fumigatus, Fusarium graminearum, Fusarium moniliforme, Penicillium chrysogenum, Penicillium corylophilum, and Stachybotrys atra. The compounds were tested in a Czapek agar medium at a concentration of 100 MUg/mL. Racemic gossypol and apogossypolone inhibited growth by up to 95%, whereas gossypolone effected 100% growth inhibition in all fungal isolates tested except A. flavus. Growth inhibition was variable during the observed time period for all tested fungi capable of growth in these treatment conditions. Gossypolone demonstrated significant aflatoxin biosynthesis inhibition in A. flavus AF13 (B(1), 76% inhibition). Apogossypolone was the most potent aflatoxin inhibitor, showing greater than 90% inhibition against A. flavus and greater than 65% inhibition against A. parasiticus (B(1), 67%; G(1), 68%). Gossypol was an ineffectual inhibitor of aflatoxin biosynthesis in both A. flavus and A. parasiticus. Both gossypol and apogossypolone demonstrated significant inhibition of ochratoxin A production (47%; 91%, respectively) in cultures of A. alliaceus. PMID- 22324795 TI - Analysis of chromosome 19q13.42 amplification in embryonal brain tumors with ependymoblastic multilayered rosettes. AB - Recently, it was reported that ependymoblastoma and embryonal tumor with abundant neuropil and true rosettes (ETANTR) show 19q13.42 amplification at a high frequency, suggesting that these tumors may constitute a single entity. As ependymoblastic rosettes are the most prominent features in both subtypes, embryonal tumor with multilayered rosettes (ETMR) was proposed, for which 19q13.42 amplification represents a specific molecular hallmark. However, ependymoblastic rosettes are not specific to ependymoblastoma and ETANTR, and are also found in a few other embryonal tumors as well as immature teratomas, and knowledge on 19q13.42 amplification in these tumors is limited. In this study, we performed fluorescence in situ hybridazation (FISH) analysis and differential polymerase chain reaction (PCR), and detected 19q13.42 amplification in three out of four ETANTR, one ependymoblastoma and one medulloepithelioma with ETANTR components, whereas none of the two atypical teratoid/rhabdoid tumors (AT/RT) with ependymoblastic rosettes nor two immature teratomas with developing neuroectodermal structures showed such amplification, suggesting that medulloepitheliomas would possibly be included in ETMR, and ependymoblastic rosettes in AT/RT do not signify that these tumors constitute ETMR. Also, we found C19MC rather than miR-371-373 was amplified in one ETANTR, suggesting that C19MC miRNA cluster seems to be more closely linked to the pathogenesis of ETMR. PMID- 22324796 TI - Bronchial inflammation induced PKCzeta over-expression: involvement in mechanical properties of airway smooth muscle. AB - Protein kinase C variants (PKCs) have been involved in the control of airway smooth muscle (ASM) tone, and abnormalities in PKC-dependent signaling have been associated with respiratory diseases such as asthma. In this study, the role of atypical PKCzeta in airway hyperresponsiveness was investigated, using an in vitro model of TNFalpha-treated human bronchi and an in vivo guinea pig model of chronic asthma. Our results demonstrated that PKCzeta-specific inhibition produced a significant increase in isoproterenol sensitivity in TNFalpha-treated bronchi and ovalbumin (OVA)-sensitized guinea pig bronchi. The role of epoxy eicosanoids, known to exert anti-inflammatory effects in lung, on PKCzeta expression and activity in these models was evaluated. An enhanced PKCzeta protein expression was delineated in TNFalpha-treated bronchi when compared with control (untreated) and epoxy-eicosanoid-treated bronchi. Measurements of Ca(2+) sensitivity, performed in TNFalpha-treated bronchi, demonstrated that treatment with myristoylated (Myr) PKCzeta peptide inhibitor resulted in significant reductions of pCa-induced tension. Epoxy-eicosanoid treatments had similar effects on Ca(2+) sensitivity in TNFalpha-treated bronchi. In control and epoxy eicosanoid-treated bronchi, the phosphorylated forms of p38MAPK and CPI-17 were significantly decreased compared with the TNFalpha-treated bronchi. An enhanced expression of PKCzeta was ascertained in our in-vivo model of allergic asthma. Hence an increased Ca(2+) sensitivity could be explained by the phosphorylation of p38-MAPK, which in turn leads to phosphorylation and activation of the CPI-17 regulatory protein. This process was reversed upon treatment with the Myr-PKCzeta peptide inhibitor. The present data provide relevant evidence regarding the role of PKCzeta in human and rodent models of airways inflammation. PMID- 22324797 TI - A comparison of the Nexfin(r) and transcardiopulmonary thermodilution to estimate cardiac output during coronary artery surgery. AB - The newly introduced Nexfin((r)) device allows analysis of the blood pressure trace produced by a non-invasive finger cuff. We compared the cardiac output derived from the Nexfin and PiCCO, using transcardiopulmonary thermodilution, during cardiac surgery. Forty patients with preserved left ventricular function undergoing elective coronary artery bypass graft surgery were studied after induction of general anaesthesia and until discharge to the intensive care unit. There was a significant correlation between Nexfin and PiCCO before (r(2) = 0.81, p < 0.001) and after (r(2) = 0.56, p < 0.001) cardiopulmonary bypass. Bland Altman analysis demonstrated the mean bias of Nexfin to be -0.1 (95% limits of agreement -0.6 to +0.5, percentage error 23%) and -0.1 (-0.8 to +0.6, 26%) l.min( 1).m(-2), before and after cardiopulmonary bypass, respectively. After a passive leg-raise was performed, there was also good correlation between the two methods, both before (r(2) = 0.72, p < 0.001) and after (r(2) = 0.76, p < 0.001) cardiopulmonary bypass. We conclude that the Nexfin is a reliable method of measuring cardiac output during and after cardiac surgery. PMID- 22324798 TI - Risk factors for drinking among HIV-positive African American adults: the depression-gender interaction. AB - BACKGROUND: Alcohol misuse disproportionately affects people living with HIV. People who struggle with alcohol are also likely to be concurrently struggling with depression. Although there is evidence linking depression to HIV, depression to alcohol, and alcohol to HIV, there is limited research that simultaneously examines the interlocking associations between all three factors. OBJECTIVE: To investigate the interaction between depression symptomatology and gender on alcohol misuse, while controlling for motivation to reduce drinking, among HIV positive African Americans. This population was examined because of their increased for developing alcohol dependence. METHODS: Data analysis was conducted on baseline survey data of HIV-positive African American adults (N = 88) who drink and were enrolled in the Project PLUS (Positive Living through Understanding and Support) intervention to examine the correlates (i.e., gender, motivation, depression) of drinking in the past 30 days. RESULTS: Hierarchical linear regression analysis showed a significant interaction between gender and depression to predict total drinks reported (R(2) = .56, p < .001). While depression was the sole predictor of drinking for men and suppressed the role of motivation, the reverse was true for women; depression was not a significant predictor after controlling for motivation to reduce drinking. CONCLUSION: African American men and women living with HIV have different risk factors for recent drinking. SCIENTIFIC SIGNIFICANCE: Understanding the link between depression, gender, and motivation to reduce drinking for HIV-positive adults with alcohol problems is crucial for the development of gender and culturally relevant treatments. PMID- 22324799 TI - Consecutive proteolytic digestion in an enzyme reactor increases depth of proteomic and phosphoproteomic analysis. AB - Analytical advantages of using multiple enzymes for sample digestion (MED), primarily an increase of sequence coverage, have been reported in several studies. However, this approach is only rarely used, mainly because it requires additional sample and mass spectrometric measurement time. We have previously described Filter Aided Sample Preparation (FASP), a type of proteomic reactor, in which samples dissolved in sodium dodecyl sulfate (SDS) are digested in an ultrafiltration unit. In FASP, such as in any other preparation protocol, a portion of sample remains after digestion and peptide elution. Making use of this fact, we here develop a protocol enabling consecutive digestion of the sample with two or three enzymes. By use of the FASP method, peptides are liberated after each digestion step and remaining material is subsequently cleaved with the next proteinase. We observed excellent performance of the ultrafiltration devices in this mode, allowing efficient separation of orthogonal populations of peptides, resulting in an increase in the numbers of identified peptides and proteins. At the low microgram level, we found that the consecutive use of endoproteinases LysC and trypsin enabled identification of up to 40% more proteins and phosphorylation sites in comparison to the commonly used one-step tryptic digestion. MED-FASP offers efficient exploration of previously unused sample material, increasing depth of proteomic analyses and sequence coverage. PMID- 22324801 TI - Minimum clinically important difference in pain, disability, and quality of life after neural decompression and fusion for same-level recurrent lumbar stenosis: understanding clinical versus statistical significance. AB - OBJECT: Spine surgery outcome studies rely on patient-reported outcome (PRO) measurements to assess treatment effect, but the extent of improvement in the numerical scores of these questionnaires lacks a direct clinical meaning. Because of this, the concept of a minimum clinically important difference (MCID) has been used to measure the critical threshold needed to achieve clinically relevant treatment effectiveness. As utilization of spinal fusion has increased over the past decade, so has the incidence of same-level recurrent stenosis following index lumbar fusion, which commonly requires revision decompression and fusion. The MCID remains uninvestigated for any PROs in the setting of revision lumbar surgery for this pathology. METHODS: In 53 consecutive patients undergoing revision surgery for same-level recurrent lumbar stenosis-associated back and leg pain, PRO measures of back and leg pain were assessed preoperatively and 2 years postoperatively, using the visual analog scale for back pain (VAS-BP) and leg pain (VAS-LP), Oswestry Disability Index (ODI), Physical and Mental Component Summary categories of the 12-Item Short Form Health Survey (SF-12 PCS and MCS) for quality of life, Zung Depression Scale (ZDS), and EuroQol-5D health survey (EQ-5D). Four established anchor-based MCID calculation methods were used to calculate MCID (average change; minimum detectable change; change difference; and receiver operating characteristic curve analysis) for 2 separate anchors (health transition index of the SF-36 and the satisfaction index). RESULTS: All patients were available for 2-year PRO assessment. Two years after surgery, a significant improvement was observed for all PROs assessed. The 4 MCID calculation methods generated a range of MCID values for each of the PROs (VAS-BP 2.2-6.0, VAS-LP 3.9 7.5, ODI 8.2-19.9, SF-12 PCS 2.5-12.1, SF-12 MCS 7.0-15.9, ZDS 3.0-18.6, and EQ 5D 0.29-0.52). Each patient answered synchronously for the 2 anchors, suggesting both of these anchors are equally appropriate and valid for this patient population. CONCLUSIONS: The same-level recurrent stenosis surgery-specific MCID is highly variable based on calculation technique. The "minimum detectable change" approach is the most appropriate method for calculation of MCIDs in this population because it was the only method to reliably provide a threshold above the 95% confidence interval of the unimproved cohort (greater than the measurement error). Based on this method, the MCID thresholds following neural decompression and fusion for symptomatic same-level recurrent stenosis are 2.2 points for VAS-BP, 5.0 points for VAS-LP, 8.2 points for ODI, 2.5 points for SF 12 PCS, 10.1 points for SF-12 MCS, 4.9 points for ZDS, and 0.39 QALYs for EQ-5D. PMID- 22324802 TI - Perioperative and delayed complications associated with the surgical treatment of cervical spondylotic myelopathy based on 302 patients from the AOSpine North America Cervical Spondylotic Myelopathy Study. AB - OBJECT: Rates of complications associated with the surgical treatment of cervical spondylotic myelopathy (CSM) are not clear. Appreciating these risks is important for patient counseling and quality improvement. The authors sought to assess the rates of and risk factors associated with perioperative and delayed complications associated with the surgical treatment of CSM. METHODS: Data from the AOSpine North America Cervical Spondylotic Myelopathy Study, a prospective, multicenter study, were analyzed. Outcomes data, including adverse events, were collected in a standardized manner and externally monitored. Rates of perioperative complications (within 30 days of surgery) and delayed complications (31 days to 2 years following surgery) were tabulated and stratified based on clinical factors. RESULTS: The study enrolled 302 patients (mean age 57 years, range 29-86) years. Of 332 reported adverse events, 73 were classified as perioperative complications (25 major and 48 minor) in 47 patients (overall perioperative complication rate of 15.6%). The most common perioperative complications included minor cardiopulmonary events (3.0%), dysphagia (3.0%), and superficial wound infection (2.3%). Perioperative worsening of myelopathy was reported in 4 patients (1.3%). Based on 275 patients who completed 2 years of follow-up, there were 14 delayed complications (8 minor, 6 major) in 12 patients, for an overall delayed complication rate of 4.4%. Of patients treated with anterior-only (n = 176), posterior-only (n = 107), and combined anterior-posterior (n = 19) procedures, 11%, 19%, and 37%, respectively, had 1 or more perioperative complications. Compared with anterior-only approaches, posterior-only approaches had a higher rate of wound infection (0.6% vs 4.7%, p = 0.030). Dysphagia was more common with combined anterior-posterior procedures (21.1%) compared with anterior-only procedures (2.3%) or posterior-only procedures (0.9%) (p < 0.001). The incidence of C-5 radiculopathy was not associated with the surgical approach (p = 0.8). The occurrence of perioperative complications was associated with increased age (p = 0.006), combined anterior-posterior procedures (p = 0.016), increased operative time (p = 0.009), and increased operative blood loss (p = 0.005), but it was not associated with comorbidity score, body mass index, modified Japanese Orthopaedic Association score, smoking status, anterior-only versus posterior-only approach, or specific procedures. Multivariate analysis of factors associated with minor or major complications identified age (OR 1.029, 95% CI 1.002-1.057, p = 0.035) and operative time (OR 1.005, 95% CI 1.002-1.008, p = 0.001). Multivariate analysis of factors associated with major complications identified age (OR 1.054, 95% CI 1.015-1.094, p = 0.006) and combined anterior-posterior procedures (OR 5.297, 95% CI 1.626-17.256, p = 0.006). CONCLUSIONS: For the surgical treatment of CSM, the vast majority of complications were treatable and without long-term impact. Multivariate factors associated with an increased risk of complications include greater age, increased operative time, and use of combined anterior-posterior procedures. PMID- 22324803 TI - Spinal dural arteriovenous fistulas and intrathecal venous drainage: correlation between digital subtraction angiography, magnetic resonance imaging, and clinical findings. AB - OBJECT: Spinal dural arteriovenous fistulas (SDAVFs) cause myelopathy through arterialization of the perimedullary venous plexus and venous congestion of the spinal cord. The authors hypothesized that the craniocaudal extent of engorgement of intrathecal draining veins between the fistula site and the point of drainage out of the thecal sac correlates with the degree of myelopathy. METHODS: A retrospective review of the authors' institution's radiology databases identified 31 patients with SDAVFs who had undergone digital subtraction angiography (DSA) and MRI examinations of the spine. The authors counted the number of vertebral body levels of spinal cord enhancement and intrathecal vessel enhancement on T1 weighted postcontrast MRI studies. They also counted the number of levels of cord hyperintensity and intrathecal flow voids on T2-weighted MRI studies. On DSA, the authors identified the number of vertebral body levels of dilated intrathecal draining veins and outflow points from intrathecal veins to epidural veins. Functional status of the patients at the time of diagnosis was assessed using the Aminoff-Logue scale (ALS). RESULTS: Enlargement of the intrathecal draining veins averaged 10 +/- 7.7 spinal levels on DSA. Patients with enlarged draining veins extending 10 or more spinal levels on DSA had worse ALS scores (mean gait 3.4, mean micturition 1.5) than patients with draining veins extending fewer than 10 levels (mean gait 1.8, mean micturition 0.6; p = 0.009 and 0.02, respectively). The number of vertebral body levels of enlarged draining veins correlated with the ALS score (gait r = 0.42, p = 0.009; and micturition r = 0.55, p = 0.0006). More extensive enlarged draining veins were associated with more spinal cord T2 hyperintensity, T2 intrathecal flow voids, and T1 vessel enhancement but not cord enhancement. CONCLUSIONS: The craniocaudal extent of enlarged intrathecal veins draining SDAVF correlates with patient functional status, providing further insight into the pathophysiology of venous hypertensive myelopathy. PMID- 22324804 TI - Recovery from spinal cord injury using naturally occurring antiinflammatory compound curcumin: laboratory investigation. AB - OBJECT: Spinal cord injury (SCI) is a debilitating disease. Primary SCI results from direct injury to the spinal cord, whereas secondary injury is a side effect from subsequent edema and ischemia followed by activation of proinflammatory cytokines. These cytokines activate the prosurvival molecule nuclear factor kappaB and generate obstacles in spinal cord reinnervation due to gliosis. Curcumin longa is an active compound found in turmeric, which acts as an antiinflammatory agent primarily by inhibiting nuclear factor-kappaB. Here, the authors study the effect of curcumin on SCI recovery. METHODS: Fourteen female Sprague-Dawley rats underwent T9-10 laminectomy and spinal cord contusion using a weight-drop apparatus. Within 30 minutes after contusion and weekly thereafter, curcumin (60 mg/kg/ml body weight in dimethyl sulfoxide) or dimethyl sulfoxide (1 ml/kg body weight) was administered via percutaneous epidural injection at the injury site. Spinal cord injury recovery was assessed weekly by scoring hindlimb motor function. Animals were killed 6 weeks postcontusion for histopathological analysis of spinal cords and soleus muscle weight evaluation. RESULTS: Curcumin treated rats had improved motor function compared with controls starting from Week 1. Body weight gain significantly improved, correlating with improved Basso Beattie-Bresnahan scores. Soleus muscle weight was greater in curcumin-treated rats than controls. Histopathological analysis validated these results with increased neural element mass with less gliosis at the contusion site in curcumin treated rats than controls. CONCLUSIONS: Epidural administration of curcumin resulted in improved recovery from SCI. This occurred with no adverse effects noted in experimental animals. Therefore, curcumin treatment may translate into a novel therapy for humans with SCI. PMID- 22324805 TI - Seed development, seed germination and seedling growth in the R50 (sym16) pea mutant are not directly linked to altered cytokinin homeostasis. AB - R50 (sym16) is a pea nodulation mutant that accumulates cytokinin (CK) in its vegetative organs. Total CK content increases as the plant ages because of the low activity of the enzyme cytokinin oxidase/dehydrogenase (CKX) responsible for CK degradation. R50 exhibits a large seed with high relative water content, and its seedling establishes itself slowly. Whether these two traits are linked to abnormal CK levels was considered here. R50 was found to have a similar germination rate but a much slower epicotyl emergence than Sparkle, its wild-type (WT). At the onset of emergence, the starch grains in R50 cotyledons were larger than those of WT; furthermore, they did not degrade as fast as in WT because of low amylase activity. No differences between the pea lines were observed in the CK forms identified during seed embryogenesis. However, while CK content compared to that of WT was reduced early in R50 embryogenesis, it was elevated later on in its dry seeds where CKX activity was low, although CKX transcript abundance remained high. Transcripts of the two known PsCKX isoforms exhibited tissue- and development-specific profiles with no detectable PsCKX2 expression in cotyledons. There were more of both transcripts in R50 roots than in WT roots, but less of PsCKX2 than PsCKX1 in R50 shoots compared to WT shoots. Thus, although there is a definite CKX post-transcriptional defect in R50 dry seeds, an abnormal CK homeostasis is not the basis of the delay in R50 seedling establishment, which we linked to abnormal amylase activity early in development. PMID- 22324806 TI - Photoluminescent color tuning in fluorene derivative/copolymer composite films based on H-bonds. AB - Reversible addition-fragmentation chain transfer (RAFT) polymerization is used to synthesize diblock and random copolymers of poly[(2-trifluoroethyl methacrylate) co-(methacrylic acid)]. Copolymer films doped with fluorene derivatives comprised of pyridine groups exhibit reversible photoluminescent (PL) color tuning by adjusting the location of fluorene derivatives in H-bonds or non-H-bonds environments. The composite films exhibit green and blue photoluminescence with and without effective H-bonding between the pyridine ring in the fluorene derivative and the carboxylic acid side group, respectively. At elevated temperatures, the H-bonded structure dissociates and the fluorene derivative migrates to the hydrophobic block in the diblock polymer, and they do not form H bonds upon cooling. However, re-formation of H-bonds also occurs upon cooling random copolymers. Moreover, adjusting the annealing temperature and the solvent annealing reversibly tunes the PL color in the diblock copolymer composite films. PMID- 22324807 TI - Imaging of protein crystals with two-photon microscopy. AB - Second-order nonlinear optical imaging of chiral crystals (SONICC), which portrays second-harmonic generation (SHG) by noncentrosymmetric crystals, is emerging as a powerful imaging technique for protein crystals in media opaque to visible light because of its high signal-to-noise ratio. Here we report the incorporation of both SONICC and two-photon excited fluorescence (TPEF) into one imaging system that allows visualization of crystals as small as ~10 MUm in their longest dimension. Using this system, we then documented an inverse correlation between the level of symmetry in examined crystals and the intensity of their SHG. Moreover, because of blue-green TPEF exhibited by most tested protein crystals, we also could identify and image SHG-silent protein crystals. Our experimental data suggest that the TPEF in protein crystals is mainly caused by the oxidation of tryptophan residues. Additionally, we found that unspecific fluorescent dyes are able to bind to lysozyme crystals and enhance their detection by TPEF. We finally confirmed that the observed fluorescence was generated by a two-photon rather than a three-photon process. The capability for imaging small protein crystals in turbid or opaque media with nondamaging infrared light in a single system makes the combination of SHG and intrinsic visible TPEF a powerful tool for nondestructive protein crystal identification and characterization during crystallization trials. PMID- 22324808 TI - Titanium/yttrium mixed metal nitride clusterfullerene TiY2N@C80: synthesis, isolation, and effect of the group-III metal. AB - Titanium/yttrium mixed metal nitride clusterfullerene (MMNCF) TiY(2)N@C(80) has been successfully synthesized, representing the first Ti-containing non-scandium MMNCF. TiY(2)N@C(80) has been isolated by multistep HPLC and characterized by various spectroscopies in combination with DFT computations. The electronic absorption property of TiY(2)N@C(80) was characterized by UV-vis-NIR spectroscopy, indicating the resemblance to that of TiSc(2)N@C(80) with broad shoulder absorptions. The optical band gap of TiY(2)N@C(80) (1.39 eV) is very close to that of TiSc(2)N@C(80) (1.43 eV) but much smaller than that of Y(3)N@C(80)(I(h), 1.58 eV). Such a resemblance of the overall absorption feature of TiY(2)N@C(80) to TiSc(2)N@C(80) suggests that TiY(2)N@C(80) has a similar electronic configuration to that of TiSc(2)N@C(80), that is, (TiY(2)N)(6+)@C(80)(6-). FTIR spectroscopic study and DFT calculations accomplish the assignment of the C(80):I(h) isomer to the cage structure of TiY(2)N@C(80), with the C(1) conformer being the lowest energy structure, which is different from the C(s) conformer assigned to TiSc(2)N@C(80). The electrochemical properties of TiY(2)N@C(80) were investigated by cyclic voltammetry, revealing the reversible first oxidation and first reduction step with E(1/2) at 0.00 and 1.13 V, respectively, both of which are more negative than those of TiSc(2)N@C(80), while the electrochemical energy gap of TiY(2)N@C(80) (1.11 V) is almost the same as that of TiSc(2)N@C(80) (1.10 V). Contrary to the reversible first reduction step, the second and third reduction steps of TiY(2)N@C(80) are irreversible, and this redox behavior is dramatically different from that of TiSc(2)N@C(80), which shows three reversible reduction steps, indicating the strong influence of the encaged group-III metal (Y or Sc) on the electronic properties of TiM(2)N@C(80) (M = Y, Sc). PMID- 22324809 TI - Self-assembly-induced formation of high-density silicon oxide memristor nanostructures on graphene and metal electrodes. AB - We report the direct formation of ordered memristor nanostructures on metal and graphene electrodes by a block copolymer self-assembly process. Optimized surface functionalization provides stacking structures of Si-containing block copolymer thin films to generate uniform memristor device structures. Both the silicon oxide film and nanodot memristors, which were formed by the plasma oxidation of the self-assembled block copolymer thin films, presented unipolar switching behaviors with appropriate set and reset voltages for resistive memory applications. This approach offers a very convenient pathway to fabricate ultrahigh-density resistive memory devices without relying on high-cost lithography and pattern-transfer processes. PMID- 22324810 TI - A mixed double negative feedback loop between the sRNA MicF and the global regulator Lrp. AB - Roughly 10% of all genes in Escherichia coli are controlled by the global transcription factor Lrp, which responds to nutrient availability. Bioinformatically, we identified lrp as one of several putative targets for the sRNA MicF, which is transcriptionally downregulated by Lrp. Deleting micF results in higher Lrp levels, while overexpression of MicF inhibits Lrp synthesis. This effect is by antisense; mutations in the predicted interaction region relieve MicF-dependent repression of Lrp synthesis, and regulation is restored by compensatory mutations. In vitro, MicF sterically interferes with initiation complex formation and inhibits lrp mRNA translation. In vivo, MicF indirectly activates genes in the Lrp regulon by repressing Lrp, and causes severely impaired growth in minimal medium, a phenotype characteristic of lrp deletion strains. The double negative feedback between MicF and Lrp may promote a switch for adequate Lrp-dependent adaptation to nutrient availability. Lrp adds to the growing list of transcription factors that are targeted by sRNAs, thus indicating that perhaps the majority of all bacterial genes may be directly or indirectly controlled by sRNAs. PMID- 22324811 TI - Conformational distributions and hydrogen bonding in gel and frozen lipid bilayers: a high frequency spin-label ESR study. AB - The ESR parameters of PC spin labels in frozen membranes do not simply represent the membrane polarity or water penetration profile. Instead, they show a distribution between hydrogen-bonded (HB) and non-hydrogen-bonded (non-HB) states, which is affected by a number of factors in the membrane composition. Similar to the exclusion of solutes from crystallizing solvents, the pure bulk gel phase excludes nitroxides, forcing acyl chains to take bent conformations. In these conformations, the nitroxide is hydrogen-bonded. Furthermore, upon gradual cooling in the supercooled gel, PC labels undergo slow lateral aggregation, resulting in a broad background signal. However, if the sample is instantly frozen, this background is replaced by the HB component. In membranes with cholesterol, the observed HB/non-HB ratio can best be described by a partition like equilibrium between nitroxides located in defects of lipid structure within the hydrophobic core and those close to the membrane surface. PMID- 22324812 TI - What do lay people want to know about the disposal of nuclear waste? A mental model approach to the design and development of an online risk communication. AB - Public participation requires the involvement of lay people in the decision making processes of issues that concern them. It is currently practiced in a variety of domains, such as transport and environmental planning. Communicating risks can be a complex task, as there may be significant differences between the risk perceptions of experts and those of lay people. Among the plethora of problems that require public involvement is the site selection of a nuclear waste disposal site in the United Kingdom, which is discussed in this article. Previous ineffective attempts to locate a site provide evidence that the problem has a strong social dimension, and studies ascribe public opposition to a loss of public trust in governmental agencies and decisionmakers, and to a lack of public understanding of nuclear waste issues. Although the mental models approach has been successfully used in the effective communication of such risks as climate change, no attempt has been made to follow a prescriptive mental model approach to develop risk communication messages that inform lay people about nuclear waste disposal. After interviewing 20 lay people and 5 experts, we construct and compare their corresponding mental models to reveal any gaps and misconceptions. The mental models approach is further applied here to identify lay people's requirements regarding what they want to know about nuclear waste, and how this information should be presented so that it is easily understood. This article further describes how the mental models approach was used in the subsequent development of an online information system for the site selection of a nuclear waste repository in the United Kingdom, which is considered essential for the improvement of public understanding and the reestablishment of trust. PMID- 22324813 TI - One- and two-dimensional translational energy distributions in the iodine-loss dissociation of 1,2-C2H4I2+ and 1,3-C3H6I2+: what does this mean? AB - Threshold photoelectron photoion coincidence (TPEPICO) has been used to study the sequential photodissociation reaction of internal energy selected 1,2 diiodoethane cations: C(2)H(4)I(2)(+) -> C(2)H(4)I(+) + I -> C(2)H(3)(+) + I + HI. In the first I-loss reaction, the excess energy is partitioned between the internal energy of the fragment ion C(2)H(4)I(+) and the translational energy. The breakdown diagram of C(2)H(4)I(+) to C(2)H(3)(+), i.e., the fractional ion abundances below and above the second dissociation barrier as a function of the photon energy, yields the internal energy distribution of the first daughter, whereas the time-of-flight peak widths yield the released translational energy in the laboratory frame directly. Both methods indicate that the kinetic energy release in the I-loss step is inconsistent with the phase space theory (PST) predicted two translational degrees of freedom, but is well-described assuming only one translational degree of freedom. Reaction path calculations partly confirm this and show that the reaction coordinate changes character in the dissociation, and it is, thus, highly anisotropic. For comparison, data for the dissociative photoionization of 1,3-diiodopropane are also presented and discussed. Here, the reaction coordinate is expected to be more isotropic, and indeed the two degrees of freedom assumption holds. Characterizing kinetic energy release distributions beyond PST is crucial in deriving accurate dissociative photoionization onset energies in sequential reactions. On the basis of both experimental and theoretical grounds, we also suggest a significant revision of the 298 K heat of formation of 1,2-C(2)H(4)I(2)(g) to 64.5 +/- 2.5 kJ mol(-1) and that of CH(2)I(2)(g) to 113.5 +/- 2 kJ mol(-1) at 298 K. PMID- 22324814 TI - Mechanistic rationalization of unusual kinetics in Pd-catalyzed C-H olefination. AB - Detailed kinetic studies and novel graphical manipulations of reaction progress data in Pd(II)-catalyzed olefinations in the presence of mono-N-protected amino acid ligands reveal anomalous concentration dependences (zero order in o-CF(3) phenylacetic acid concentration, zero order in oxygen pressure, and negative orders in both olefin and product concentrations), leaving the catalyst concentration as the sole positive driving force in the reaction. NMR spectroscopic studies support the proposal that rate inhibition by the olefinic substrate and product is caused by formation of reversible off-cycle reservoirs that remove catalyst from the active cycle. NMR studies comparing the interaction between the catalyst and substrate in the presence and absence of the ligand suggest that weak coordination of the ligand to Pd prevents formation of an inactive mixed acetate species. A fuller understanding of these features may lead to the design of more efficient Pd(II) catalysts for this potentially powerful C H functionalization reaction. PMID- 22324815 TI - Multiple domains of the tobacco mosaic virus p126 protein can independently suppress local and systemic RNA silencing. AB - Small RNA-mediated RNA silencing is a widespread antiviral mechanism in plants and other organisms. Many viruses encode suppressors of RNA silencing for counter defense. The p126 protein encoded by Tobacco mosaic virus (TMV) has been reported to be a suppressor of RNA silencing but the mechanism of its function remains unclear. This protein is unique among the known plant viral silencing suppressors because of its large size and multiple domains. Here, we report that the methyltransferase, helicase, and nonconserved region II (NONII) of p126 each has silencing-suppressor function. The silencing-suppression activities of methyltransferase and helicase can be uncoupled from their enzyme activities. Specific amino acids in NONII previously shown to be crucial for viral accumulation and symptom development are also crucial for silencing suppression. These results suggest that some viral proteins have evolved to possess modular structural domains that can independently interfere with host silencing, and that this may be an effective mechanism of increasing the robustness of a virus. PMID- 22324817 TI - Identification of adducts between an odoriferous volatile thiol and oxidized grape phenolic compounds: kinetic study of adduct formation under chemical and enzymatic oxidation conditions. AB - HPLC-MS and (1)H, (13)C, and 2D NMR analyses were used to identify new addition products between 3-sulfanylhexan-1-ol (3SH) and o-quinones derived from (+) catechin, (-)-epicatechin, and caftaric acid. The kinetics of formation of these adducts were monitored in a wine model solution and in a must-like medium by HPLC UV-MS with the aim of understanding the chemical mechanism involved in reactions between volatile thiols and o-quinones. One o-quinone-caftaric acid/3SH adduct, three o-quinone-(+)-catechin/3SH adducts, and three o-quinone-(-)-epicatechin/3SH adducts were characterized. Caftaric acid was oxidized faster than (-) epicatechin and (+)-catechin when these phenolic compounds were incubated in a one-component mixture with polyphenoloxidase (PPO) in the presence of 3SH. Consequently, o-quinone-caftaric acid formed adducts with 3SH more rapidly than o quinone-(+)-catechin and o-quinone-(-)-epicatechin in the absence of other nucleophilic species. Furthermore, o-quinone-(-)-epicatechin reacted faster than o-quinone-(+)-catechin with 3SH. Sulfur dioxide decreased the yield of adduct formation to a significant extent. Under chemical oxidation conditions, the rates and yields of adduct formation were lower than those observed in the presence of PPO, and o-quinone-caftaric acid was slightly less reactive with 3SH, compared to oxidized flavan-3-ols. The identification of o-quinone-caftaric acid/3SH and o quinone-(+)-catechin/3SH adducts in a must matrix suggests that the proposed reaction mechanism is responsible for 3SH loss in dry wines during their vinification and aging process. PMID- 22324818 TI - Botulinum toxin for headache. PMID- 22324819 TI - Above- and below-ground responses of Calamagrostis purpurea to UV-B radiation and elevated CO2 under phosphorus limitation. AB - UV-B radiation and elevated CO2 may impact rhizosphere processes through altered below-ground plant resource allocation and root exudation, changes that may have implications for nutrient acquisition. As nutrients limit plant growth in many habitats, their supply may dictate plant response under elevated CO2. This study investigated UV-B exposure and elevated CO2 effects, including interactions, on plant growth, tissue chemistry and rooting responses relating to P acquisition. The sub-arctic grass Calamagrostis purpurea was subjected to UV-B (0 or 3.04 kJ m 2 day-1) and CO2 (ambient 380 or 650 ppmv) treatments in a factorial glasshouse experiment, with sparingly soluble P (0 or 0.152 mg P per plant as FePO4) a further factor. It was hypothesized that UV-B exposure and elevated CO2would change plant resource allocation, with CO2 mitigating adverse responses to UV-B exposure and aiding P uptake. Plant biomass and morphology, tissue composition and rhizosphere leachate properties were measured. UV-B directly affected chemical composition of shoots and interacted with CO2 to give a greater root biomass. Elevated CO2 altered the composition of both shoots and roots and increased shoot biomass and secondary root length, while leachate pH decreased. Below-ground responses to CO2 did not affect P acquisition although P limitation progressively reduced leachate pH and increased secondary root length. Although direct plant growth, foliar composition and below-ground nutrient acquisition responses were dominated by CO2 treatments, UV-B modified these CO2 responses significantly. These interactions have implications for plant responses to future atmospheric conditions. PMID- 22324820 TI - Long-term safety and effectiveness of drug-eluting stents compared to bare metal stents in ST elevation myocardial infarction: findings from the Guthrie Health Off-label Stent (GHOST) Registry. AB - BACKGROUND: Multiple randomized trials and observational studies have shown drug eluting stents (DES) to be safe and effective at 3-year follow-up in stent thrombosis (ST)-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). However, outcomes data beyond 3 4 years after DES implantation are sparse. METHODS: We studied 554 STEMI patients who underwent successful PCI with either DES or bare metal stent (BMS). Primary study end-points were time to occurrence of ST and the composite of death or myocardial infarction (MI). Secondary end-points were time to occurrence of major adverse cardiac events (MACEs) and discrete events that comprise MACE (death, MI, and target vessel revascularization [TVR]). Outcomes of the DES and BMS groups were assessed by survival analysis and multivariable Cox regression. RESULTS: There were 205 (37%) patients who received DES and 349 (63%) patients who received BMS. At a median follow-up of 41.4 months after PCI, there were no differences in the unadjusted incidence of ST (ST, 3.4 vs. 4.3%, log-rank P = 0.61) and MI (6.8% vs. 8%, P = 0.61) between DES versus BMS groups, respectively. However, DES implantation was associated with lower unadjusted incidence of death or MI (11% vs. 23.5%, P = 0.0002), MACE (16% vs. 34%, P < 0.0001), death (6.3% vs. 17%, P = 0.0004), and TVR (9.8% vs. 18%, P = 0.008) than BMS implantation. In multivariable analyses, DES implantation was associated with significantly lower incidence of MACE (adjusted HR = 0.47 [95% CI: 0.31-0.76], P = 0.0007) than BMS implantation. CONCLUSION: In our study of STEMI patients, DES implantation was safer than BMS implantation and was associated with lower MACE at long-term follow-up. PMID- 22324821 TI - A new approach to winning: insulin-like growth factor-I signaling in competitive sport. PMID- 22324823 TI - Clinical and electrophysiologic characteristics of antidromic tachycardia in children with Wolff-Parkinson-White syndrome. AB - BACKGROUND: Antidromic reciprocating tachycardia (ART) is a rare form of wide complex tachycardia in children with Wolff-Parkinson-White syndrome (WPW). The incidence and electrophysiologic characteristics of ART in children with WPW have not been well described. METHODS: A multicenter retrospective analysis of all patients with WPW undergoing electrophysiology (EP) study from 1990 to 2009 was performed. Patients with clinical or inducible ART were included. RESULTS: A total of 1,147 patients with WPW underwent EP study and 30 patients had ART (2.6%) and were the subject of this analysis. The mean age was 16+/-3 years, weight was 65+/-16 kg, and tachycardia cycle length was 305+/-55 ms. There were two patients (7%) with congenital heart disease (both with Ebstein's anomaly). Four patients (13%) had more than one accessory pathway (AP). The location of the AP was left sided in 53% of patients and right sided in 47%, with septal location and left lateral pathways most commonly involved. AP conduction was found to be high risk in 17 patients (57%). Ablation was not attempted in two patients (7%) due to proximity to the HIS and risk of heart block. Ablation was acutely successful in 93% of the patients in whom it was attempted. CONCLUSIONS: ART is a rare finding in children undergoing EP study. Over half of the patients with ART were found to be high risk and multiple AP were uncommon. Unlike the adult population, ART occurred commonly with septal APs. PMID- 22324824 TI - What is the best pre-operative risk stratification tool for major adverse cardiac events following elective vascular surgery? A prospective observational cohort study evaluating pre-operative myocardial ischaemia monitoring and biomarker analysis. AB - Although brain natriuretic peptide has been shown to be superior to the revised cardiac risk index for risk stratification of vascular surgical patients, it remains unknown whether it is superior to alternative dynamic risk predictors, such as other pre-operative biomarkers (C-reactive protein and troponins) or myocardial ischaemia monitoring. The aim of this prospective observational study was to determine the relative clinical utility of these risk predictors for the prediction of postoperative cardiac events in elective vascular surgical patients. Only pre-operative troponin elevation (OR 56.8, 95% CI 6.5-496.0, p < 0.001) and brain natriuretic peptide above the optimal discriminatory point (OR 6.0, 95% CI 2.7-12.9, p < 0.001) were independently associated with cardiac events. Both brain natriuretic peptide and troponin risk stratification significantly improved overall net reclassification (74.6% (95% CI 51.6%-97.5%) and 38.5% (95% CI 22.4-54.6%, respectively)); however, troponin stratification decreased the correct classification of patients with cardiac complications ( 59%, p < 0.001). Pre-operative brain natriuretic peptide evaluation was the only clinically useful predictor of postoperative cardiac complications. PMID- 22324825 TI - Comparative analysis of cone and rod transducins using chimeric Galpha subunits. AB - The molecular nature of transducin-alpha subunits (Galpha(t)) may contribute to the distinct physiology of cone and rod photoreceptors. Biochemical properties of mammalian cone Galpha(t2) subunits and their differences with rod Galpha(t1) are largely unknown. Here, we examined properties of chimeric Galpha(t2) in comparison with its rod counterpart. The key biochemical difference between the rod- and cone-like Galpha(t) was ~10-fold higher intrinsic nucleotide exchange on the chimeric Galpha(t2). Presented mutational analysis suggests that weaker interdomain interactions between the GTPase (Ras-like) domain and the helical domain in Galpha(t2) are in part responsible for its increased spontaneous nucleotide exchange. However, the rates of R*-dependent nucleotide exchange of chimeric Galpha(t2) and Galpha(t1) were equivalent. Furthermore, chimeric Galpha(t2) and Galpha(t1) exhibited similar rates of intrinsic GTPase activity as well as similar acceleration of GTP hydrolysis by the RGS domain of RGS9. Our results suggest that the activation and inactivation properties of cone and rod Galpha(t) subunits in an in vitro reconstituted system are comparable. PMID- 22324826 TI - Raman spectroscopy-based sensitive and specific detection of glycated hemoglobin. AB - In recent years, glycated hemoglobin (HbA1c) has been increasingly accepted as a functional metric of mean blood glucose in the treatment of diabetic patients. Importantly, HbA1c provides an alternate measure of total glycemic exposure due to the representation of blood glucose throughout the day, including post prandially. In this article, we propose and demonstrate the potential of Raman spectroscopy as a novel analytical method for quantitative detection of HbA1c, without using external dyes or reagents. Using the drop coating deposition Raman (DCDR) technique, we observe that the nonenzymatic glycosylation (glycation) of the hemoglobin molecule results in subtle but discernible and highly reproducible changes in the acquired spectra, which enable the accurate determination of glycated and nonglycated hemoglobin using standard chemometric methods. The acquired Raman spectra display excellent reproducibility of spectral characteristics at different locations in the drop and show a linear dependence of the spectral intensity on the analyte concentration. Furthermore, in hemolysate models, the developed multivariate calibration models for HbA1c show a high degree of prediction accuracy and precision--with a limit of detection that is a factor of ~15 smaller than the lowest physiological concentrations encountered in clinical practice. The excellent accuracy and reproducibility achieved in this proof-of-concept study opens substantive avenues for characterization and quantification of the glycosylation status of (therapeutic) proteins, which are widely used for biopharmaceutical development. We also envision that the proposed approach can provide a powerful tool for high throughput HbA1c sensing in multicomponent mixtures and potentially in hemolysate and whole blood lysate samples. PMID- 22324827 TI - Intraribbon heterojunction formation in ultranarrow graphene nanoribbons. AB - Graphene nanoribbons-semiconducting quasi-one-dimensional graphene structures have great potential for the realization of novel electronic devices. Recently, graphene nanoribbon heterojunctions-interfaces between nanoribbons with unequal band gaps-have been realized with lithographic etching techniques and via chemical routes to exploit quantum transport phenomena. However, standard fabrication techniques are not suitable for ribbons narrower than ~5 nm and do not allow to control the width and edge structure of a specific device with atomic precision. Here, we report the realization of graphene nanoribbon heterojunctions with lateral dimensions below 2 nm via controllable dehydrogenation of polyanthrylene oligomers self-assembled on a Au(111) surface from molecular precursors. Atomistic simulations reveal the microscopic mechanisms responsible for intraribbon heterojunction formation. We demonstrate the capability to selectively modify the heterojunctions by activating the dehydrogenation reaction on single units of the nanoribbons by electron injection from the tip of a scanning tunneling microscope. PMID- 22324828 TI - Adsorption, capillary bridge formation, and cavitation in SBA-15 corrugated mesopores: a Derjaguin-Broekhoff-de Boer analysis. AB - A Derjaguin-Broekhoff-de Boer analysis of adsorption and desorption in SBA-15 mesoporous silica is presented, using realistic geometrical models that account for the pore corrugation in these materials. The model parameters are derived from independent electron tomography and small-angle scattering characterization. A geometrical characteristic of the pore that is found to be important for adsorption is the corrugation length, l(C), which describes the longitudinal size of the geometrical defects along a given pore. Capillary bridges are possible only for large values of l(C). The results are explained in terms of two spinodal and two equilibrium pressures, characterizing the wide and the narrow sections of the pores. Simplified analytical expressions are obtained, which provide necessary conditions for bridge formation and for cavitation in terms of the radii of the narrow and wide sections of the pores, as well as of l(C). Quite generally, the results show that the deviation of the pore shape from that of ideal cylinders is key to understanding adsorption and desorption in corrugated mesopores, notably in SBA-15. PMID- 22324829 TI - Cell-mediated and direct gene therapy for bone regeneration. AB - INTRODUCTION: Bone regeneration is required for the treatment of fracture non/delayed-unions and bone defects. However, most current treatment modalities have limited efficacy, and newer therapeutic strategies, such as gene therapy, have substantial benefit for bone repair and regeneration. AREAS COVERED: This review discusses experimental and clinical applications of cell-mediated and direct gene therapy for bone regeneration. The review covers literature on this subject from 2000 to February 2012. EXPERT OPINION: Direct gene therapy using various viral and non-viral vectors of cell-mediated genes has been demonstrated to induce bone regeneration, although use of such vectors has shown some risk in human application. Osteoinductive capability of a number of progenitor cells isolated from bone marrow, fat, muscle and skin tissues, has been demonstrated by genetic modification with osteogenic genes. Cell-mediated gene therapy using such osteogenic gene-expressing progenitor cells has shown promising results in promoting bone regeneration in extensive animal work in recent years. PMID- 22324830 TI - Reduction of fractional exhaled nitric oxide (FENO) and its variation by mouth wash. AB - INTRODUCTION: Although fractional exhaled nitric oxide (FENO) measurement is a widely used method to assess eosinophilic bronchial inflammation, knowledge on extrabronchial factors affecting measurement results is still limited. Our aim was to study the eventual modifying effect of mouth wash on FENO values and their variability. MATERIALS AND METHODS: A total of 16 healthy Caucasian women performed FENO measurements with a chemiluminescence analyzer according to ATS guidelines (2005), with an exhalation flow rate of 50 ml/s against a flow resistor. On the first day three successive FENO measurements were performed: first after mouth wash with water containing sodium and potassium bicarbonates, and thereafter twice without mouth wash. On the second day, the FENO measurement was first performed without mouth wash, then with preceding mouth wash twice, and finally without preceding mouth wash. Each FENO measurement consisted of three measurements with the average reported and the time interval between the FENO measurements was 10 minutes on both days. RESULTS: The FENO level increased significantly in the subsequent measurements performed without mouth wash (p < 0.01), when the baseline measurement was performed with mouth wash. On the second day, the FENO level decreased significantly in measurements performed with preceding mouth wash, compared with the first measurement without preceding mouth wash (p < 0.01). CONCLUSION: The results indicate a slight but statistically significant decreasing effect of mouth wash on the FENO. The findings suggest that mouth wash prior to FENO measurement could standardize the measurement procedure, by decreasing the effect of NO produced in the mouth on the measurement result. PMID- 22324831 TI - Moderate temperature alterations affect Gram-negative immune signalling in ex vivo whole blood. AB - BACKGROUND: Alterations in body temperature may influence immune system function and consequently affect the risk of infection and inflammatory diseases. Lipopolysaccharide (LPS) from gram-negative bacteria induces production of inflammatory cytokines after ligand binding to Toll-like receptor 4 (TLR4) on immune cells (especially monocytes/ macrophages). Our aim was to explore how clinically relevant hypo- and hyperthermia affect this signalling in an ex vivo whole blood model, and investigate if the cytokine response was correlated with monocyte TLR4 expression level. METHODS: Blood from 11 healthy volunteers was incubated with LPS 10 ng/ml for 6 h at 33, 37 or 40 degrees C. The concentrations of selected pro-inflammatory (tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta) and anti-inflammatory (IL-10) cytokines were measured in plasma, and the surface expression of TLR4 was quantified on CD14 + monocytes. RESULTS: Monocyte TLR4 expression and plasma IL-1beta were inversely related to temperature. The TNF-alpha production was unaffected by hypothermia but increased significantly during hyperthermia, whereas plasma IL-10 was significantly reduced during both hypo- and hyperthermic incubation. No correlation was found between TLR4 expression and cytokine concentrations. During hypothermia, the TNF-alpha/IL 10 and IL-1beta/IL-10 ratios increased seven and nine times, respectively. Hyperthermia increased the TNF-alpha/IL-10 ratio, but to a lesser extent (doubling), whereas the IL-1beta/IL-10 ratio remained unchanged. CONCLUSION: Hypothermia significantly changed the cytokine ratios in the pro-inflammatory direction. In comparison, the effect of hyperthermia was sparse, with a modest increase in the TNF-alpha/IL-10 ratio only. No association was found between LPS stimulated cytokine production and TLR4 expression on CD14 + monocytes. PMID- 22324832 TI - Chemodynamics of metal complexation by natural soft colloids: Cu(II) binding by humic acid. AB - The chemodynamics of Cu(II) complexation by humic acid is interpreted in terms of recently developed theory for permeable charged nanoparticles. Two opposing electric effects are operational with respect to the overall rate of association, namely, (i) the conductive enhancement of the diffusion of Cu(2+), expressed by a coefficient f(el), which accounts for the accelerating effect of the negative electrostatic field of the humic particle on the diffusive transport of metal ions toward it, and (ii) the ionic Boltzmann equilibration with the bulk solution, expressed by a factor f(B), which quantifies the extent to which Cu(2+) ions accumulate in the negatively charged particle body. These effects are combined in the probability of outer-sphere metal-site complex formation and the covalent binding of the metal ion by the complexing site (inner-sphere complex formation) as in the classical Eigen mechanism. Overall "experimental" rate constants for CuHA complex formation, k(a), are derived from measurements of the thermodynamic stability constant, K*, and the dissociation rate constant, k(d)*, as a function of the degree of metal ion complexation, theta. The resulting k(a) values are found to be practically independent of theta. They are also compared to theoretical values; at an ionic strength of 0.1 mol dm(-3), the rate of diffusive supply of metal ions toward the particles is comparable to the rate of inner-sphere complex formation, indicating that both processes are significant for the observed overall rate. As the ionic strength decreases, the rate of diffusive supply becomes the predominant rate-limiting process, in contrast with the general assumption made for complexes with small ligands that inner-sphere dehydration is the rate-limiting step. The results presented herein also resolve the discrepancy between experimentally observed and predicted dissociation rate constants based on the above assumption. PMID- 22324833 TI - Alternative interdomain configurations of the full-length MMP-2 enzyme explored by molecular dynamics simulations. AB - Conformational freedom between the different domains of the matrix metalloproteinase family of enzymes has been repeatedly invoked to explain the mechanism of hydrolysis of some of their most complex macromolecular substrates. This proposed interdomain motion has been experimentally confirmed to occur in solution for matrix metalloproteinases MMP-1, MMP-9, and MMP-12. In this work, we computationally assess the likely conformational freedom in aqueous solution of the full-length form of the MMP-2 enzyme in the absence of its pro-peptide domain. To this end, we perform molecular dynamics (MD) simulations and approximate free energy analyses in four different arrangements of the protein domains that correspond to (a) the compact conformation observed in the X-ray structure; (b) an initially elongated structure in which the hemopexin (HPX) domain is separated from the catalytic (CAT) and fibronectin domains; and (c-d) two alternative conformations suggested by protein-protein docking calculations. Overall, our results indicate that the interdomain flexibility is very likely a general property of the MMP-2 enzyme in solution. PMID- 22324834 TI - Using the WHO 2006 child growth standard to assess the growth and nutritional status of rural south Indian infants. AB - BACKGROUND: The WHO 2006 child growth standard is advocated in India, although the conformity of the growth of Indian infants to the WHO standard has only been assessed at cross-sectional points. AIM: To assess the implications of using the WHO standard in rural India and to investigate the factors responsible for any departure from optimal growth, as shown in the WHO standard. SUBJECTS AND METHODS: Mixed-effects models were applied to serial weight and length data from 384 rural south Indian infants. Unadjusted and adjusted (for, among other things, breastfeeding and maternal education) estimates were converted to Z-scores and the risks of underweight, wasting and stunting using the WHO standard compared to the NCHS 1977 child growth reference were calculated. RESULTS: Weight growth was more similar to the WHO standard than the NCHS reference and in late infancy the WHO standard was less likely to classify underweight (RR at 15 months = 0.45; 95% CI = 0.31-0.65). Adjusting the serial data shifted the curves 0.25 Z-scores closer to the median of either chart; variations in household socioeconomic status and morbidity were largely responsible for this shift. CONCLUSION: In late infancy, the WHO standard will allow a more focused intervention effort and use of resources for targeting programmes at infants most at risk of malnutrition. PMID- 22324835 TI - Risk factors for diabetes, but not for cardiovascular disease, are associated with family history of Type 2 diabetes in subjects from central Mexico. AB - BACKGROUND: Independent of obesity, family history of type 2 diabetes mellitus (FHT2DM) is another important risk factor for developing diabetes. AIM: To establish the association among FHT2DM, risk factors for diabetes and cardiovascular disease in subjects from central Mexico. SUBJECTS AND METHODS: Clinical and biochemical studies were performed in 383 first-degree relatives of patients with type 2 diabetes and 270 subjects unrelated to patients with type 2 diabetes-all subjects were from the city of Puebla in central Mexico. Logistic regressions were used to assess the association between FHT2DM and metabolic parameters. Cardiovascular risk was classified by dyslipidemia and the Framingham Risk Score (FRS). RESULTS: FHT2DM was associated with risk factors for diabetes, such as increased fasting insulin levels (OR = 1.731, 95% CI = 1.041-2.877), decreased insulin sensitivity (OR = 1.951, 95% CI = 1.236-3.080) and pre-diabetes (OR = 1.63, 95% CI = 1.14-2.33). FHT2DH was not associated with risk factors for cardiovascular disease, such as dyslipidemia (OR = 1.12, 95% CI = 0.70-1.79) and FRS (OR = 0.74, 95% CI = 0.40-1.36) when adjusted for gender, age, smoking and obesity. CONCLUSION: Diabetic risk factors, but not cardiovascular disease risk factors, are associated with a positive family history of diabetes in subjects from central Mexico, independent of the presence of obesity. PMID- 22324836 TI - Predictive ability of serum high-molecular-weight adiponectin in combination with serum insulin and serum C-reactive protein for the presence of metabolic syndrome. AB - BACKGROUND AND AIMS: Metabolic syndrome (MetS) is an insulin-resistance syndrome deeply associated with obesity. The association between MetS and several clinical factors, including serum levels of adiponectin, C-reactive protein and insulin, was examined. SUBJECTS AND METHODS: The study was performed in 219 men aged 43.2 +/- 6.6 years, who were employees of a company. The study measured the serum high sensitivity C-reactive protein (CRP) as an inflammatory marker, serum insulin as a marker of insulin resistance and serum high-molecular-weight adiponectin (HMW adipo), in addition to the serum levels of liver enzymes and uric acid. MetS was diagnosed according to the National Cholesterol Education Programme ATPIII criteria. RESULTS: Log-transformed serum ALT, HMW-adipo, insulin and uric acid were found to be significantly related to the presence/absence of Mets by logistic regression analysis, with odds ratios (95% confidence intervals) of 25.9 (3.3-204.4), 0.10 (0.02-0.56), 7.5 (1.6-34.1) and 1.5 (1.04-2.1), respectively. CONCLUSION: Serum high HMW-adipo level was significantly negatively related to the presence of MetS, independently of the serum levels of insulin, liver enzymes and uric acid. Among the markers examined, serum HMW-adipo and ALT were considered as markers for MetS. PMID- 22324837 TI - Association of CFTR gene mutation with bronchial asthma and its severity in Indian children: a case-control study. AB - BACKGROUND: Asthma is a complex genetic disorder. Several genes have been found associated with asthma. The cystic fibrosis transmembrane conductance regulator (CFTR) gene is one of them. AIM: To assess the association of CFTR gene mutation with asthma and its severity as per GINA guidelines. SUBJECTS AND METHODS: This was a hospital-based case-control study. Excluded from cases and controls were those with clinically suspected cystic fibrosis or sweat chloride level>60 mmol/L or suffering from other respiratory diseases. Included were 200 cases and 180 controls, aged 5 months to 15 years. Screening was done for CFTR gene mutations; DeltaF508, G542X, G551D, R117H and W1282X using the ARMS-PCR method. RESULTS: DeltaF508 was found in three (1.5%) cases and two (1.1%) controls (p = 0.739), G542X in nine (4.5%) cases and five (2.8%) controls (p = 0.374), R117H in one (0.5%) case and one (0.6%) control (p = 0.940) and G551D in twelve (6.0%) cases and two (1.1%) controls (p = 0.012). Individuals carrier for G551D mutation had increased risk for persistent asthma (p = 0.006). Percent predicted FEV1 (p = 0.014) and FVC (p = 0.028) were significantly lower among carriers as compared to non-carriers. CONCLUSION: Significantly higher frequency of G551D mutation among asthma patients compared with controls suggests that this mutation may increase risk for the disease and also its severity. PMID- 22324838 TI - Obesity is associated with insulin resistance and components of the metabolic syndrome in Lebanese adolescents. AB - BACKGROUND: Prevalence of metabolic syndrome (MS) in obese adolescents has been reported to range between 18-42%, depending on country of origin, thus suggesting an ethnic-based association between obesity and MS. AIM: This study aims to investigate the magnitude of the association between obesity, insulin resistance and components of MS among adolescents in Lebanon. SUBJECTS AND METHODS: The sample included 263 adolescents at 4(th) and 5(th) Tanner stages of puberty (104 obese; 78 overweight; 81 normal weight). Anthropometric, biochemical and blood pressure measurements were performed. Body fat was assessed using dual-energy X ray absorptiometry. RESULTS: According to International Diabetes Federation criteria, MS was identified in 21.2% of obese, 3.8% of overweight and 1.2% of normal weight subjects. The most common metabolic abnormalities among subjects having MS were elevated waist circumference (96.2%), low HDL (96.2%) and hypertriglyceridemia (73.1%). Insulin resistance was identified in all subjects having MS. Regression analyses showed that percentage body fat, waist circumference and BMI were similar in their ability to predict the MS in this age group. CONCLUSIONS: MS was identified in a substantial proportion of Lebanese obese adolescents, thus highlighting the importance of early screening for obesity-associated metabolic abnormalities and of developing successful multi component interventions addressing adolescent obesity. PMID- 22324839 TI - Socio-economic and demographic factors affecting the Composite Index of Anthropometric Failure (CIAF). AB - BACKGROUND: The present cross-sectional study evaluates the utility of the Composite Index of Anthropometric Failure (CIAF) over conventional nutritional indices for nutritional assessment. It also assesses the impact of various socio economic and demographic factors on the CIAF. SUBJECTS AND METHODS: Height, weight, age, socio-economic and demographic data were recorded from 3444 children (1682 boys; 1762 girls) aged 1-12 years and residing in Darjeeling district, West Bengal, India. The conventional anthropometric indices and CIAF were compared with the NCHS reference data to assess prevalence of under-nutrition. A multinomial logistic regression was used to assess the impact of different socio economic and demographic variables on the CIAF. RESULTS: Prevalence of under nutrition was observed to be 21.5% (wasting), 43.3% (stunting) and 52.0% (underweight). This increased to 63.6% using the CIAF. The multinomial logistic regression odds showed that children suffering from double and multiple failures were significantly associated with the socio-economic and demographic variables. CONCLUSION: The CIAF provides more precision in identifying the nutritionally vulnerable segment of the population. The disaggregation of CIAF has an adequate potential to enhance the efficacy of a nutritional intervention programme by identifying double or multiple failures. PMID- 22324840 TI - CYP2D6 gene variants in urban/admixed and Amerindian populations of Venezuela: pharmacogenetics and anthropological implications. AB - BACKGROUND: Differences in genes encoding enzymes involved in the biotransformation of a large number of compounds, such as CYP2D6, are related to inter-individual and inter-ethnic variability in the metabolism of many drugs, which have also been linked to susceptibility to cancer and other health outcomes. Therefore, populations are likely to benefit from inclusion in pharmacogenetic research studies. AIM: To determine the frequency of functionally important allele variants of CYP2D6 gene in a sample of an Urban/admixed and five Amerindian Venezuelan populations. SUBJECTS AND METHODS: DNA of 328 unrelated volunteers was analysed for the presence of CYP2D6 *2, *3, *4, *5, *6 and *10 variants. RESULTS: The frequency in the Urban/admixed population for *2, *3, *4, *5, *6 and *10 alleles was 37.9%, 0%, 13.4%, 2.0%, 1.2% and 4.0%, respectively. In the Bari population, the prevalence of *4 allele associated with decreased enzyme activity was observed in 42.5%, whereas the poor metabolizer genotype *4/*4 was found in 25%. In the Panare, Pemon, Warao and Wayuu populations the *4 allele was found in 5.4%, 2.5%, 1.7% and 4.2%, respectively. The *10 allele frequency found in Amerindians (0.0-6.3%) was lower than reported for Asians. CONCLUSION: The results are consistent with the known genetic admixture origin of most Venezuela populations. Nevertheless, the observed significant differences among Amerindians highlight the need for pharmacogenetic studies taking into account biogeographical and anthropological considerations. PMID- 22324841 TI - Influence of evolutionary forces and demographic processes on the genetic structure of three Croatian populations: a maternal perspective. AB - BACKGROUND: Many Croatian islands are examples of genetic isolates, with low level of heterozygosity and high level of inbreeding, due to practice of endogamy. AIM: The aim was to study the genetic structure of two insular and one mainland population through high-resolution phylogenetic analysis of mitochondrial DNA (mtDNA). SUBJECTS AND METHODS: MtDNA polymorphisms were explored in 300 unrelated individuals from Mljet, Lastovo and the coastal city of Dubrovnik, based on SNP polymorphisms. RESULTS: All mtDNA haplogroups found in the sample were of typical European origin. However, the frequency distribution of their subclades differed significantly from other Croatian and European populations. MtDNA haplotype analysis revealed only two possible founder lineages on Mljet and six on Lastovo, accounting for almost half of the sample on both islands. The island of Mljet also has the lowest reported haplotype and nucleotide diversity among Croatian isolates and the island of Lastovo, a new sublineage of a usually quite rare U1b clade. CONCLUSION: The results can be explained by the effect evolutionary forces have on genetic structure, which is in line with the specific demographic histories of the islands. An additional research value of these two island isolates is the appearance of certain Mendelian disorders, highlighting their importance in epidemiological studies. PMID- 22324842 TI - Estimating total body fat using a skinfold prediction equation in Brazilian children. AB - BACKGROUND: The double burden of obesity and underweight is increasing in developing countries and simple methods for the assessment of fat mass in children are needed. AIM: To develop and validate a new anthropometric predication equation for assessment of fat mass in children. SUBJECTS AND METHODS: Body composition was assessed in 145 children aged 9.8 +/- 1.3 (SD) years from Sao Paulo, Brazil using dual energy X-ray absorptiometry (DEXA) and skinfold measurements. The study sample was divided into development and validation sub-sets to develop a new prediction equation for FM (PE). RESULTS: Using multiple linear regression analyses, the best equation for predicting FM (R(2) = 0.77) included body weight, triceps skinfold, height, gender and age as independent variables. When cross-validated, the new PE was valid in this sample (R(2) = 0.80), while previously published equations were not. CONCLUSION: The PE was more valid for Brazilian children that existing equations, but further studies are needed to assess the validity of this PE in other populations. PMID- 22324843 TI - Neck circumference is an accurate and simple index for evaluating overweight and obesity in Han children. AB - BACKGROUND: The prevalence of obesity has reached alarming levels in recent years. Neck circumference (NC) has been shown to be an indicator of central adiposity. AIM: The purpose of this study was to analyse whether NC can be used to determine overweight and obesity in Han Chinese children. SUBJECTS AND METHODS: In 2011, anthropometric measurements were gathered in a cross-sectional, population-based study of 2847 Han children aged 7-12 years. Overweight and obesity were defined according to the 2004 Chinese obesity task force definition. Receiver operating characteristic curve analyses were conducted to assess the accuracy of NC as a diagnostic test for elevated body mass index (BMI) (overweight and obesity). RESULTS: The prevalence of overweight and obesity in boys was 18.0% and 26.0%, respectively, and 11.7% and 15.7%, respectively, for girls. The mean NC in boys was significantly greater than in girls (29.2 +/- 3.1 cm vs 28.1 +/- 2.8 cm, p < 0.001). NC was significantly correlated with age, BMI and waist circumference in both boys and girls (p < 0.001 for all comparisons). NC cut-off values for elevated BMI were between 27.4~31.3 cm in boys and 26.3~31.4 cm in girls. The sensitivities were 75.5~86.7% in boys and 80.0~92.5% in girls. The specificities were 73.9~91.7% in boys and 74.7~93.3% in girls. CONCLUSION: The present study demonstrates that NC is a simple, inexpensive and accurate measurement that may be used to identify overweight and obesity in Han children. PMID- 22324844 TI - Polymorphisms influencing muscle phenotypes in North-African and Spanish populations. AB - AIM: The purpose of this study was to determine the allelic and genotypic frequency distribution of the C34T mutation in the muscle isoform of the adenosine monophosphate deaminase 1 (AMPD1) gene and of the missense substitution K153R in the myostatin (GDF8) gene in one Spanish and two North African populations. METHOD: One sample of 98 individuals was genotyped from the South of Spain (Alpujarra) and two samples from Morocco (77 Berbers and 78 Arabs). RESULTS: The frequency of the AMPD1 C34T mutation was lower in Berbers (0.071) compared with the Alpujarra cohort (0.153, p = 0.018). The GDF8 K153R substitution showed little variability among the three cohorts. CONCLUSIONS: Studies with larger cohorts and other ethnic groups are needed to corroborate that there does not exist any major variability in the genotype distribution of genes associated with muscle phenotypes in the South-Eastern Mediterranean area. PMID- 22324845 TI - Dietary flavonoid naringenin induces regulatory T cells via an aryl hydrocarbon receptor mediated pathway. AB - The aryl hydrocarbon receptor (AhR), a transcription factor mediating xenobiotic detoxification, plays a considerable role in regulatory T cell (Treg) induction. Tregs regulate the immune system, thus suppressing allergies and autoimmune diseases. This study aims to identify new types of antiallergic dietary factors, with focus on the flavonoids with potential AhR agonistic activity. Among 25 dietary flavonoid samples tested using a reporter assay, 8 showed marked induction of AhR-dependent transcriptional activity. The subsequent T cell proliferation suppression assay identified naringenin as the only sample capable of stimulating Treg induction; notably, this induction was eliminated by cotreatment with AhR antagonists. Indeed, naringenin induced CD4(+)Foxp3(+) Tregs, irrespective of the presence of the transforming growth factor-beta (TGF beta), indicating that the conventional TGF-beta-dependent signaling pathway might not be involved. PMID- 22324846 TI - Integrating a top-down and a bottom-up approach: formal and informal risk handling strategies in a utility company. AB - In this study, we bring together a top-down and a bottom-up approach of risk handling. We do so by conceptualizing and qualitatively and quantitatively measuring formal and informal risk-handling strategies in a Dutch utility company. We conceive of formal risk handling as regulating, training, and educating safety and enforcing rule compliance, while we distinguish three different informal risk-handling strategies: discretionary specialization, tacit knowledge, and taking personal responsibility. We show that the formal risk handling strategy and the three informal risk-handling strategies can be measured separately. Hence, we have validated the measurement of all four strategies derived from two different risk-handling approaches. Moreover, we have demonstrated that the perceived use of the four strategies has different effects on unsafe behavior: formal risk handling and tacit knowledge decrease it, discretion increases it, and taking personal responsibility has no effect on unsafe behavior. PMID- 22324847 TI - 2-(2-Methoxyphenyl)-1,3-dimethyl-1H-benzoimidazol-3-ium iodide as a new air stable n-type dopant for vacuum-processed organic semiconductor thin films. AB - 2-(2-Methoxyphenyl)-1,3-dimethyl-1H-benzoimidazol-3-ium iodide (o-MeO-DMBI-I) was synthesized and employed as a strong n-type dopant for fullerene C(60), a well known n-channel semiconductor. The coevaporated thin films showed a maximum conductivity of 5.5 S/cm at a doping concentration of 8.0 wt% (14 mol%), which is the highest value reported to date for molecular n-type conductors. o-MeO-DMBI-I can be stored and handled in air for extended periods without degradation and is thus promising for various organic electronic devices. PMID- 22324848 TI - Amide analogues of CD1d agonists modulate iNKT-cell-mediated cytokine production. AB - Invariant natural killer T (iNKT) cells are restricted by the non-polymorphic MHC class I-like protein, CD1d, and activated following presentation of lipid antigens bound to CD1d molecules. The prototypical iNKT cell agonist is alpha galactosyl ceramide (alpha-GalCer). CD1d-mediated activation of iNKT cells by this molecule results in the rapid secretion of a range of pro-inflammatory (Th1) and regulatory (Th2) cytokines. Polarization of the cytokine response can be achieved by modifying the structure of the glycolipid, which opens up the possibility of using CD1d agonists as therapeutic agents for a range of diseases. Analysis of crystal structures of the T-cell receptor-alpha-GalCer-CD1d complex led us to postulate that amide isosteres of known CD1d agonists should modulate the cytokine response profile upon iNKT-cell activation. To this end, we describe the synthesis and biological activity of amide analogues of alpha-GalCer and its non-glycosidic analogue threitol ceramide (ThrCer). All of the analogues were found to stimulate murine and human iNKT cells by CD1d-mediated presentation to varying degrees; however, the thioamide and carbamate analogues of ThrCer were of particular interest in that they elicited a strongly polarized cytokine response (more interferon-gamma (IFN-gamma), no interleukin-4 (IL-4)) in mice. While the ThrCer-carbamate analogue was shown to transactivate natural killer (NK) cells, a mechanism that has been used to account for the preferential production of IFN gamma by other CD1d agonists, this pathway does not account for the polarized cytokine response observed for the thioamide analogue. PMID- 22324849 TI - An interplay between Centrin2 and Centrin4 on the bi-lobed structure in Trypanosoma brucei. AB - Centrins are conserved calcium-binding proteins important for various regulatory functions. In procyclic Trypanosoma brucei, TbCentrin2 and TbCentrin4 have distinct effects on cell division but both localize to the basal bodies that seed the flagellum, and a bi-lobed structure important for organelle duplication and cell division. Here we show that TbCentrin2 and TbCentrin4 both bind to the basal bodies and bi-lobed structure through the conserved C-terminal domain. Molecular genetic manipulation of TbCentrin4 levels greatly affects TbCentrin2 association with the bi-lobed structure. Using established synchronization methods, TbCentrin2 expression level is shown to be relatively constant throughout the cell cycle while TbCentrin4 level fluctuates, decreasing most during early S phase when the bi-lobe undergoes duplication. These results thus suggest a co ordinated action between these two centrin proteins, where the cell cycle dependent TbCentrin4 expression could regulate the abundance of TbCentrin2 on the bi-lobed structure. PMID- 22324850 TI - Migraine at altitude--is it due to hypoxia or hypobaria? PMID- 22324851 TI - Solar UV-B effects on PSII performance in Betula nana are influenced by PAR level and reduced by EDU: results of a 3-year experiment in the High Arctic. AB - The long-term and diurnal responses of photosystem II (PSII) performance to near ambient UV-B radiation were investigated in High Arctic Betula nana. We conducted an UV exclusion experiment with five replicated blocks consisting of open control (no filter), photosynthetic active radiation and UV-B transparent filter control (Teflon), UV-B-absorbing filter (Mylar) and UV-AB-absorbing filter (Lexan). Ethylenediurea (EDU), a chemical normally used to protect plants against ozone injury, was sprayed on the leaves both in the field and in an additional laboratory study to investigate if EDU mitigated the effects of UV-B. Chlorophyll a fluorescence induction curves were used for analysis of OJIP test parameters. Near-ambient UV-B radiation reduced across season maximum quantum yield (TR(o) /ABS = F(v) /F(m)), approximated number of active PSII reaction center (RC/ABS) and the performance index (PI(ABS)), despite improved leaf screening against UV-B with higher content of UV-B-absorbing compounds and a lower specific leaf area. EDU application counteracted the negative impact of UV-B on TR(o) /ABS, RC/ABS and PI(ABS) . This indicates that the mechanisms behind UV-B and ozone damage share some common features. The midday depression was present in all treatments, but TR(o) /ABS and PI(ABS) were persistently lower in near-ambient UV-B compared to UV-B reduction. The recovery phase was particularly impaired in near-ambient UV-B and interactive effects between treatment * hour raised TR(o) /ABS, RC/ABS and PI(ABS) higher in reduced UV-B compared to near-ambient UV-B. This demonstrates current solar UV-B to reduce the PSII performance both on a daily as well as a seasonal basis in this High Arctic species. PMID- 22324852 TI - Exploration of health perceptions and assistive technology use by driving status as related to transportation independence in New Delhi, India. AB - PURPOSE: This study investigates travel tendencies among people with disabilities and senior citizens in New Delhi, India to reveal relationships between the desire for transportation independence, use of assistive technology for mobility, travel frequency, and satisfaction with available modes of transportation. METHOD: Study volunteers received invitations to complete a one-time, three-part questionnaire. The survey included an assessment battery developed by the Quality of Life Technology Engineering Research Center, questions featured in the 2002 National Transportation Availability and Use Survey, and a variation on the PARTS/M and FABS/M questionnaires. RESULTS: 80 study participants completed the questionnaire, and were grouped according to driving status as No Driving Experience (NDE), Ceased Driving (CD), and Continue To Drive (CTD). Participants in the NDE group were less likely to use transportation more than twice daily. However, the CD group had the lowest perceived value for available transportation options, with transportation use comparable to the CTD group and an enduring desire to continue driving. CONCLUSIONS: Study findings suggest an inner drive for transportation independence. The rise of driving culture internationally presents driver rehabilitation services with challenges due to the need for vehicle modifications and driving assessment using manual transmission automobiles, scooters, and motorcycles. PMID- 22324853 TI - Sequence effects on translesion synthesis of an aminofluorene-DNA adduct: conformational, thermodynamic, and primer extension kinetic studies. AB - The DNA sequence effect is an important structural factor for determining the extent and nature of carcinogen-induced mutational and repair outcomes. In this study, we used two 16-mer template sequences, TG*A [d(5'-CTTCTTG*ACCTCATTC-3')] and CG*A [d(5'-CTTCTCG*ACCTCATTC-3')], to study the impact of the 5'-flanking nucleotide (T vs C) on aminofluorene (AF)-induced stacked (S)/major groove (B)/wedge (W) conformational heterogeneity during a simulated translesion synthesis. In addition, we probed the sequence effect on nucleotide insertion efficiencies catalyzed by the Klenow fragment (exonuclease-deficient) of DNA polymerase I. Our (19)F NMR/ICD/DSC results showed that AF in the CG*A duplex sequence adopts a greater population of S-conformer than the TG*A sequence. We found that the S conformer of CG*A thermodynamically favors insertion of A over C at the lesion site (n). Significant stalling occurred at both the prelesion (n - 1) and lesion (n) sites; however, the effect was more persistent for the S conformer of CG*A than TG*A at the lesion site (n). Kinetics show that relative nucleotide insertion frequencies (f(ins)) were greater for TG*A than the S conformer of CG*A for either dCTP or dATP at the lesion site (n), and the insertion rate was significantly reduced at immediate upstream base pairs (n, n + 1). Taken together, the results provide insight into how the mutagenic AF could exhibit an S/B/W equilibrium in the active site of a polymerase, causing different mutations. This work represents a novel structure-function relationship in which adduct structure is directly linked to nucleotide insertion efficiency in a conformation-specific manner during translesion DNA synthesis. PMID- 22324854 TI - How does litter quality affect the community of soil protists (testate amoebae) of tropical montane rainforests? AB - Litter quality and diversity are major factors structuring decomposer communities. However, little is known on the relationship between litter quality and the community structure of soil protists in tropical forests. We analyzed the diversity, density, and community structure of a major group of soil protists of tropical montane rainforests, that is, testate amoebae. Litterbags containing pure and mixed litter of two abundant tree species at the study sites (Graffenrieda emarginata and Purdiaea nutans) differing in nitrogen concentrations were exposed in the field for 12 months. The density and diversity of testate amoebae were higher in the nitrogen-rich Graffenrieda litter suggesting that nitrogen functions as an important driving factor for soil protist communities. No additive effects of litter mixing were found, rather density of testate amoebae was reduced in litter mixtures as compared to litterbags with Graffenrieda litter only. However, adding of high-quality litter to low-quality litter markedly improved habitat quality, as evaluated by the increase in diversity and density of testate amoebae. The results suggest that local factors, such as litter quality, function as major forces shaping the structure and density of decomposer microfauna that likely feed back to decomposition processes. PMID- 22324855 TI - Openly accessible microfluidic liquid handlers for automated high-throughput nanoliter cell culture. AB - Cell culture is typically performed in Petri dishes, with a few million cells growing together, or in microwell plates with thousands of cells in each compartment. When the throughput of each experiment, especially of screening based assays, is increased, even using microliter solution per well will cost a considerable amount of cells and reagents. We took a rational approach to reduce the volume of each cell culture chamber. We designed and fabricated a poly(dimethylsiloxane) based liquid pipet chip to deliver and transfer nanoliter (50-500 nL) samples and reagents with high accuracy and robustness. A few tens to a few hundreds of cells can be successfully seeded, transferred, passaged, transfected, and stimulated by drugs on a microwell chip using this pipet chip automatically. We have used this system to test the cell growth dynamically, observed the correlation between the culture conditions and cell viabilities, and quantitatively evaluated cell apoptosis induced by cis-diammineplatinum(II) dichloride (cisplatin). This system shows great potential to facilitate large scale screening and high-throughput cell-array based bioassays with the volume of each individual cell colony at the nanoliter level. PMID- 22324856 TI - Under what conditions is it ethical to offer incentives to encourage drug-using women to use long-acting forms of contraception? AB - AIMS: To stimulate debate by examining ethical issues raised by Project Prevention, a US-based organization that offers $US300 to addicted individuals who agree to either undergo surgical sterilization or use long-acting forms of contraception. METHOD: An analysis of key ethical questions raised by Project Prevention. RESULTS: The important issues for debate are: (i) what are the reproductive rights of drug-using women; (ii) does a substantial cash incentive undermine the ability of addicted women to make free and informed decisions about long-term contraception; and (iii) how can we best assist addicted women to access good reproductive health care and obtain treatment for their addiction? CONCLUSIONS: We need more research on ways in which small non-cash incentives for reversible methods of contraception could be used in a morally acceptable and effective way to promote the sexual, reproductive and general health of addicted women. PMID- 22324858 TI - Ordered arrays of gold nanostructures from interfacially assembled Au@PNIPAM hybrid nanoparticles. AB - In this Article, we report on the assembly of hybrid Au@PNIPAM core-shell particles at the air/water interface, their transfer onto solid substrates, and the controlled combustion of the organic material to produce arrays of gold nanoparticles. A detailed investigation on the assembly behavior of such soft hybrid colloids at the air/water interface was performed by correlating the surface pressure-area isotherms with SEM and AFM images from samples transferred at different surface pressures. The hybrid particles display a complex behavior at the interface, and we could distinguish three distinct phases with varying interparticle spacings at different compression. The transfer process presented enables the decoration of topologically structured substrates with gold nanoparticle arrays, and the order of the initial monolayers is retained in the arrays of inorganic gold nanoparticles. The change in monolayer morphology upon compression can therefore be used to tailor the interparticle distance between approximately 650 and 300 nm without exchanging the colloids. More sophisticated gold nanostructures can be patterned into symmetric arrays using a similar protocol, which we demonstrate for nanostars and nanorods. PMID- 22324859 TI - Higher than expected estradiol levels in aromatase inhibitor-treated, postmenopausal breast cancer patients. AB - OBJECTIVE: Vaginal estradiol is considered contraindicated in aromatase inhibitor (AI)-treated patients because of the risk of elevated estrogen levels. This leaves limited treatment options for patients experiencing gynecological symptoms. However, in clinical practice, no precise estimation has been performed of circulating estrogens and aromatase index in postmenopausal breast cancer patients on long-lasting AI or tamoxifen treatment. METHODS: Steroid hormones were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) and extraction radioimmunoassay (RIA). Postmenopausal AI-treated patients (n =33) were compared with tamoxifen-treated patients (n =34) and controls without vaginal treatment (n =56), with vaginal estradiol (n =25), or with estriol (n =11) treatment. RESULTS: By use of LC-MS/MS, median (range) estradiol plasma concentrations were 16.7 (2.4-162.6), 31.0 (13.4-77.1), 27.2 (7.8-115.8) and 33.3 (20.3-340.1) pmol/l in AI-treated breast cancer patients, tamoxifen-treated breast cancer patients, postmenopausal controls and postmenopausal controls on vaginal estradiol, respectively. The AI-treated group and subgroups had significantly lower estradiol and estrone concentrations than all other groups (p <0.05). There was extensive interindividual variation in estradiol concentration within the AI-treated group, measured using both LC-MS/MS (2.3-182.0 pmol/l) and extraction RIA (2.4-162.6 pmol/l). The AI-treated group had lower aromatase index compared to all other groups (p <0.05-0.001). CONCLUSION: Circulating estrogen levels may have been underestimated in previous longitudinal studies of AI treated breast cancer patients. Additional studies are required to further evaluate the role of circulating estrogens in breast cancer patients suffering from gynecological symptoms. PMID- 22324860 TI - Preparticipation screening and prevention of sudden cardiac death in athletes: implications for primary care. AB - PURPOSES: The purposes of this article are to explore the mechanism of sudden cardiac death (SCD) in young athletes and examine how preparticipation screenings help identify precipitating cardiac abnormalities. Electrocardiogram (ECG) testing has been implicated to play an important role in detecting subtle abnormalities that may cause SCD, but the routine implementation of this diagnostic tool remains a debate among experts. DATA SOURCES: This report was compiled by reviewing the scientific literature on SCD in athletes, preparticipation exams, and current screening guidelines using CINAHL, MEDLINE, and PubMed search engines. CONCLUSIONS: Although the American Heart Association guidelines do not include ECG testing for preparticipation screenings, the implementation of routine ECG testing for preparticipation sports physicals is effective in preventing SCD in athletes. IMPLICATIONS FOR PRACTICE: Primary care providers should be aware of current guidelines for screening patients for heart diseases that predispose them to SCD and their legal obligations to be sure these athletes are safe. The implementation of ECG testing will assist in the decision whether to disqualify an athlete from participation as a result of preexisting cardiac conditions, and ultimately preventing the untimely death of a young athlete. PMID- 22324861 TI - Energy drinks: what is all the hype? The dangers of energy drink consumption. AB - PURPOSE: To describe the adverse effects associated with energy drink consumption among adolescents and young adults. DATA SOURCES: Review of literature utilizing Medscape, the Internet, MD Consult, and CINAHL. The following search terms were used: Energy drinks, caffeine, guarana, taurine, ginseng, sugar, and caffeine toxicity. Search was limited to English language sources from 2005 to 2010. CONCLUSIONS: The popularity of energy drinks and the rapid growth of their excessive consumption among adolescents and young adults have brought about great concern in regards to overall health and well-being. Caffeine, which is readily available to minors, is the most commonly used psychoactive substance in the world and imposes a potentially harmful influence on health, academic performance, and personal adjustments. Teens and young adults account for nearly $2.3 billion of energy drink sales. Adolescents and young adults are often unaware that various products, such as energy drinks, herbal medications, and various other medications that promote alertness, contain caffeine. When these products are taken together, caffeine toxicity and severe adverse effects can occur. IMPLICATIONS FOR PRACTICE: Practitioners need to be aware of the consequences of energy drink consumption and be prepared to provide appropriate patient education. PMID- 22324862 TI - Examining factors influencing patient satisfaction with nurse practitioners in rural urgent care centers. AB - PURPOSE: To examine if demographic factors influence patients' self reports of satisfaction with care provided by nurse practitioners (NPs) in rural urgent care centers (UCCs). DATA SOURCES: Data were collected between December 2009 and February 2010 using an 18-item self-report survey from a convenience sample of 53 patients in two rural UCCs. CONCLUSIONS: No statistical significance was noted in regards to patient satisfaction for the demographic factors age, gender, country of upbringing, or education level. Presence of health insurance was a significant factor, with uninsured patients rating higher levels of satisfaction. However, based on patients' responses to role clarity for this survey, it is evident that there continues to be insufficient public understanding of the role of NPs. IMPLICATIONS FOR PRACTICE: The future of the NP relies on patient approval as well as acceptance of the role. This study joins the pioneering efforts towards describing what patient satisfaction is and supports NPs serving as providers in rural, nonprimary care venues. By identifying influential factors of satisfaction, NPs can bridge the gap between availability of quality care versus a lack of access and inform policy changes in the future. PMID- 22324863 TI - Implementation of a skin cancer screening tool in a primary care setting: a pilot study. AB - PURPOSE: (a) To explore whether there would be an increase in nurse practitioner (NP) skin cancer screening knowledge following an educational program. (b) To determine whether NPs report enhanced physical assessment skills when applying a screening tool in clinical practice. (c) To determine whether use of a skin cancer screening tool improves NP documentation during student physical exams. DATA SOURCES: Data were gathered in phase one of the study through a pretest, educational intervention, posttest, and program evaluation. Phase two gathered data from a prestudy patient chart analysis, and a poststudy chart analysis following implementation of a skin cancer screening tool. A convenience sample of six female NPs age of 40-64 years was drawn from a single college health center in the northeast. CONCLUSIONS: There is demonstrated efficacy educating NPs in proper documentation/early detection of skin cancer among young adults in a college health, primary care setting. Findings revealed a 223.4% increase in proper documentation of skin cancer screening and skin cancer patient education. IMPLICATIONS FOR PRACTICE: Educating NPs in skin cancer identification, screening and use of a skin cancer screening tool is an effective way to improve quality of services provided to patients and quality of NP documentation. PMID- 22324864 TI - Storied experiences of nurse practitioners managing prehypertension in primary care. AB - PURPOSE: The purpose of this study was to explore the nurse practitioner (NP) experience with caring for prehypertensive patients. Lifestyle modifications are the primary recommendation for management of prehypertension. Given the historical foundation of health promotion and disease prevention as a fundamental component of NP professional identity, gaining insight into the experience of caring for prehypertensive patients in the current healthcare environment is valuable to the profession, patients, and communities. Therefore, the NP role in health promotion and disease prevention related to prehypertension was explored as well. DATA SOURCES: Narrative inquiry was the chosen methodology to gather narrative accounts of eight NPs caring for prehypertensive patients in primary care. The three-dimensional narrative inquiry space was used to guide the researcher during data analysis. CONCLUSIONS: Three themes emerged from the NPs' narratives: realities of practice, ambiguous role identity, and bridging models. Time constraints, financial considerations, and bridging the nursing and medical models while adapting to practice environments were barriers identified as components of the NP experience caring for patients with prehypertension. IMPLICATIONS FOR PRACTICE: This study revealed that caring for prehypertensive patients is a complex and multilayered experience. PMID- 22324865 TI - Nurse practitioner attitudes and treatment practices for childhood overweight: how do rural and urban practitioners differ? AB - PURPOSE: Pediatric overweight and obesity has become an epidemic problem of our nation. Nurse practitioners (NPs) are exposed to overweight pediatric patients on a regular basis. The purpose of this study was to investigate NP attitudes toward pediatric overweight and obesity and explore their current diagnosis and treatment practices. Differences between rural and urban NPs were also investigated. DATA SOURCES: Survey data were gathered from 1088 family and pediatric NPs from the American Academy of Nurse Practitioners member list randomly. Only family and pediatric NPs were included in the sample. CONCLUSIONS: NPs in the sample believed that pediatric overweight and obesity are problems in need of treatment, but also reported not assessing and diagnosing the condition per current guidelines. Initiation of treatment was reported at very low rates. Rural NPs reported having fewer referral resources than urban NPs. IMPLICATIONS FOR PRACTICE: NPs are in an ideal position to properly assess, diagnose, and treat pediatric overweight and obesity. The findings suggest that more education on these topics is necessary for NPs. Rural NPs reported fewer referral services, and may need to have more knowledge about how to provide obesity treatment services in their own practice settings due to this disparity. PMID- 22324866 TI - Older adult osteoarthritis pain management: results from the 2008 National Ambulatory Medical Care Survey. AB - PURPOSE: To describe practitioners' prescription of recommended initial osteoarthritis (OA) pain treatments for older adults. DATA SOURCES: A secondary data analysis was conducted with the 2008 National Ambulatory Medical Care Survey (NAMCS) that was completed by practitioners in ambulatory medical care settings. Of the 28,741 office visits, 9314 were by adult patients age 60 or older, and 871 of those visits involved a painful joint. Only 128 were also by people with practitioner-documented OA. Of those 128 visits, 21 (16.1%) were prescribed exercise and/or acetaminophen and were not prescribed non-steroidal anti inflammatory agents (NSAIDS). No complementary alternative medical treatments were prescribed. Older adults with and without documented OA had a mean of at least four office visits with the practitioner during the past year. CONCLUSIONS: OA may be under-diagnosed, under-reported, or overshadowed by co-morbid medical conditions. Older adults with persistent OA pain are at increased risk for adverse events from prescribed NSAIDs. Safe and effective multimodal pain treatments need to be prescribed for older adults with persistent OA pain. IMPLICATIONS FOR PRACTICE: Referral to a rheumatologist or pain management specialist should be considered when pain intensity and/or pain interference with daily activities remains moderate or greater. PMID- 22324867 TI - Teaching inhaler use in chronic obstructive pulmonary disease patients. AB - PURPOSE: To review barriers to the successful use of inhalers in patients with chronic obstructive pulmonary disease (COPD), and the role of the nurse practitioner (NP) in facilitating optimum inhaler use. DATA SOURCES: Review of the national and international scientific literature. CONCLUSIONS: Pharmacologic treatment of COPD patients comprises mainly inhaled medications. Incorrect use of inhalers is very common in these individuals. Some of the consequences of poor inhaler technique include reduced therapeutic dosing, medication adherence, and disease stability, which can lead to increased morbidity, decreased quality of life, and a high burden on the healthcare system. Knowledgeable evaluation and frequent reassessment of inhaler use coupled with education of patients, caregivers, and healthcare professionals can significantly improve the benefits COPD patients derive from inhaled therapy. IMPLICATIONS FOR PRACTICE: Patient education is vital for correct use of inhalers and to ensure the effectiveness of inhaled medications. The NP has a critical role in assessing potential barriers to successful learning by the patient and improving inhaler technique and medication management. The NP can also facilitate success with inhaled medications by providing up-to-date inhaler education for other healthcare team members, who may then act as patient educators. PMID- 22324868 TI - Nanomagnetic sensing of blood plasma protein interactions with iron oxide nanoparticles: impact on macrophage uptake. AB - One of the first biointeractions of magnetic nanoparticles with living systems is characterized by nanoparticle-protein complex formation. The proteins dynamically encompass the particles in the protein corona. Here we propose a method based on nanomagnetism that allows a specific in situ monitoring of interactions between iron oxide nanoparticles and blood plasma. Tracking the nanoparticle orientation through their optical birefringence signal induced by an external magnetic field provides a quantitative real-time detection of protein corona at the surface of nanoparticles and assesses eventual onset of particle aggregation. Since some of the plasma proteins may cause particle aggregation, we use magnetic fractionation to separate the nanoparticle clusters (induced by "destabilizing proteins") from well-dispersed nanoparticles, which remain isolated due to a stabilizing corona involving other different types of proteins. Our study shows that the "biological identity" (obtained after the particles have interacted with proteins) and aggregation state (clustered versus isolated) of nanoparticles depend not only on their initial surface coating, but also on the concentration of plasma in the suspension. Low plasma concentrations (which are generally used in vitro) lead to different protein/nanoparticle complexes than pure plasma, which reflects the in vivo conditions. As a consequence, by mimicking in vivo conditions, we show that macrophages can perceive several different populations of nanoparticle/protein complexes (differing in physical state and in nature of associated proteins) and uptake them to a different extent. When extrapolated to what would happen in vivo, our results suggest a range of cell responses to a variety of nanoparticle/protein complexes which circulate in the body, thereby impacting their tissue distribution and their efficiency and safety for diagnostic and therapeutic use. PMID- 22324869 TI - Evidence-based optometry and in-practice research. PMID- 22324870 TI - In-practice (in-office) optometric research. PMID- 22324871 TI - College guidelines for examining patients at risk from glaucoma. PMID- 22324873 TI - Promoting agriculture proteome research activities in the Asia and Oceania region. PMID- 22324874 TI - An assessment of the accuracy of pulse oximeters. AB - Peripheral pulse oximetry has become a core monitoring modality in most fields of medicine. Pulse oximeters are used ubiquitously in operating theatres, hospital wards, outpatient clinics and general practice surgeries. This study used a portable spectrometer (Lightman((r)), The Electrode Co. Ltd., Monmouthshire, UK) to measure the emission spectra of the two light emitting diodes within the pulse oximeter sensor and to determine the accuracy of 847 pulse oximeters currently in use in 29 NHS hospitals in the UK. The standard manufacturing claim of accuracy for pulse oximeters is +/- 2-3% over the range of 70-100% S(p)O(2). Eighty-nine sensors (10.5%) were found to have a functional error of their electrical circuitry that could cause inaccuracy of measurement. Of the remaining 758 sensors, 169 (22.3%) were found to have emission spectra different from the manufacturers' specification that would cause an inaccuracy in saturation estimation of > 4% in the range of 70-100% saturation. This study has demonstrated that a significant proportion of pulse oximeter sensors may be inaccurate. PMID- 22324875 TI - Composition of transgenic soybean seeds with higher gamma-linolenic acid content is equivalent to that of conventional control. AB - gamma-Linolenic acid (GLA) has been used as a general nutraceutical for pharmacologic applications, particularly in the treatment of skin conditions such as eczema. Four transgenic soybean lines that produce GLA at high yields (4.21% of total fatty acids, up to 1002-fold) were generated through the stable insertion of the Delta-6-fatty acid desaturase gene isolated from Borago officinalis into the genome of a conventional soybean cultivar. As part of the safety assessment of genetically engineered crops, the transgenic soybean seeds were compared with their parental soybean seeds (nontransgenic) by applying the principle of substantial equivalence. Compositional analyses were conducted by measuring the fatty acids, proximate analysis (moisture, crude protein, crude fat, carbohydrates, TDF, and ash contents), amino acids, lectins, and trypsin inhibitor activity. The present results showed that the specific transgenic cultivar studied was similar to the conventional control. PMID- 22324876 TI - Scaled correlation analysis: a better way to compute a cross-correlogram. AB - When computing a cross-correlation histogram, slower signal components can hinder the detection of faster components, which are often in the research focus. For example, precise neuronal synchronization often co-occurs with slow co-variation in neuronal rate responses. Here we present a method - dubbed scaled correlation analysis - that enables the isolation of the cross-correlation histogram of fast signal components. The method computes correlations only on small temporal scales (i.e. on short segments of signals such as 25 ms), resulting in the removal of correlation components slower than those defined by the scale. Scaled correlation analysis has several advantages over traditional filtering approaches based on computations in the frequency domain. Among its other applications, as we show on data from cat visual cortex, the method can assist the studies of precise neuronal synchronization. PMID- 22324877 TI - Computational study on reaction mechanisms and kinetics of RNCN (R = H, F, Cl, Br, CH3) radicals with NO. AB - We carried out a computational study of radical reactions of RNCN (R = H, F, Cl, Br, CH(3)) + NO to investigate how the substitution can influence their corresponding energy barriers and rate coefficients. The preferable reactive sites of RNCN radicals with various substituents are calculated by employing the Fukui functions and hard-and-soft acid-and-base theory, which were generally proved to be successful in the prediction and interpretation of regioselectivity in various types of electrophilic and nucleophilic reactions. Our calculated results clearly show that if the substituted RNCN radical has electron-donating substituent (for R = CH(3)), its corresponding barrier heights for transition states will be substantially decreased. The possible explanations of the observed increase and/or decrease in the energy barriers for the varied substituted RNCN radicals are also analyzed in this article. PMID- 22324878 TI - Short communication: Does interleukin-28B single nucleotide polymorphisms influence the natural history of hepatitis B? AB - Single nucleotide polymorphisms (SNP) nearby the IL28B gene have been associated with spontaneous hepatitis C virus (HCV) clearance and response to interferon based therapies in both monoinfected and HIV-coinfected patients. However, its impact on spontaneous clearance of HBV (the pathogenesis of which is also related to interferon) is less known. A case-control study was performed. Cases were 49 HIV(+) patients with chronic hepatitis B (HBsAg(+) for more than 6 months) who had been genotyped for the rs12979860 SNP (protective CC genotype). One control for each case was chosen among HIV patients with anti-HBs and anti-HBc. Controls were matched for gender and coinfection with HCV. Most patients were male (90%) and the median (IQR) age was 42.6 (39-46.7) years. Eighteen (36.7%) were also coinfected by HCV. Among HBsAg(+) patients, 19 (41.3%) were HBeAg(+) and 13 (26.5%) were also infected with hepatitis delta (HDV). No differences were found in the distribution of the CC genotype between patients with chronic hepatitis B and those who spontaneously cured hepatitis B: 59.2% vs. 44.9%; p=0.3. Thus, the interleukin-28B (IL-28B) genotype does not seem to have a role in the development of chronic hepatitis B among HIV-infected patients. PMID- 22324879 TI - CD133+ cells as a therapeutic target for kidney diseases. AB - INTRODUCTION: The availability of antibodies recognizing the glycosylation dependent expression of AC133 epitope of CD133 allowed the identification of stem cells in different human tissues. In the kidney, CD133 has been identified as a marker of progenitor cells within the nephron, both in the cortex and in the inner medulla, showing features of non-differentiated mesenchymal progenitors. In addition, CD133 may be considered a marker of renal repair, as the hypoxic microenvironment occurring after injury may favor the acquirement of CD133 progenitor properties by cells of the nephron. AREAS COVERED: Areas covered in this review include CD133 expression that, in renal pathology, has been related to excessive proliferation and/or reduced differentiation of renal progenitors, which occurs in polycystic kidney disease and glomerular diseases. Also included are data from literature, which by contrast, indicate CD133 cannot be considered a promising marker for renal cancer stem cells. EXPERT OPINION: CD133 could be of interest as a possible therapeutic target for nonmalignant renal pathology. Selective targeting of CD133 may allow pharmacological approaches to control proliferation or induce differentiation of CD133+ cells. In the light of a possible role of CD133 in the regulation of the anaerobic glycolytic metabolism, CD133 modulation could be of therapeutic interest in renal regeneration or diseases. Successful exploitation of CD133 will nevertheless require a better understanding of its molecular function. PMID- 22324880 TI - Role of pseudouridine in structural rearrangements of helix 69 during bacterial ribosome assembly. AB - As part of the central core domain of the ribosome, helix 69 of 23S rRNA participates in an important intersubunit bridge and contacts several protein translation factors. Helix 69 is believed to play key roles in protein synthesis. Even though high-resolution crystal structures of the ribosome exist, the solution dynamics and roles of individual nucleotides in H69 are still not well defined. To better understand the influence of modified nucleotides, specifically pseudouridine, on the multiple conformational states of helix 69 in the context of 50S subunits and 70S ribosomes, chemical probing analyses were performed on wild-type and pseudouridine-deficient bacterial ribosomes. Local structural rearrangements of helix 69 upon ribosomal subunit association and interactions with its partner, helix 44 of 16S rRNA, are observed. The helix 69 conformational states are also magnesium-dependent. The probing data presented in this study provide insight into the functional role of helix 69 dynamics and regulation of these conformational states by post-transcriptional pseudouridine modification. PMID- 22324881 TI - Methanogenic biodegradation of two-ringed polycyclic aromatic hydrocarbons. AB - Polycyclic aromatic hydrocarbons (PAH) are widespread in methane-rich subsurface environments, such as oil reservoirs and fuel-contaminated aquifers; however, little is known about the biodegradation of these compounds under methanogenic conditions. To assess the metabolism of PAH in the absence of electron acceptors, a crude oil-degrading methanogenic enrichment culture was tested for the ability to biodegrade naphthalene, 1-methylnaphthalene (1-MN), 2-methylnaphthalene (2 MN), and 2, 6-dimethylnaphthalene (2, 6-diMN). When methane was measured as an indicator of metabolism, nearly 400 MUmol of methane was produced in the 2-MN- and 2, 6-diMN-amended cultures relative to substrate-unamended controls, which is close to the amount of methane stoichiometrically predicted based on the amount of substrate added (51-56 MUmol). In contrast, no substantial methane was produced in the naphthalene- and 1-MN-amended enrichments. In time course experiments, metabolite analysis of enrichments containing 2-MN and 2, 6-diMN revealed the formation of 2-naphthoic acid and 6-methyl-2-naphthoic acid, respectively. Microbial community analysis by 454 pyrosequencing revealed that these PAH-utilizing enrichments were dominated by archaeal members most closely affiliated with Methanosaeta and Methanoculleus species and bacterial members most closely related to the Clostridiaceae, suggesting that these organisms play an important role in the methanogenic metabolism of the substituted naphthalenes in these cultures. PMID- 22324882 TI - Using computer-assisted method to teach children with intellectual disabilities handwashing skills. AB - PURPOSE: To motivate children with intellectual disabilities (ID) to learn handwashing and improve their performance by using computer-assisted teaching method. METHOD: A teaching program was implemented using a computerized teaching station with faucet, soap dispenser and towel dispenser as user interface. In response to the children's actions, animations were shown on the computer screen of the teaching station. A controlled study was conducted to compare the effectiveness of the proposed method (study group) with that of the convention teaching method (control group). Both groups of subjects attended a 30-min handwashing lesson twice per week for 2 months. Their performance was evaluated using a handwashing task checklist and a learning motivation questionnaire, and by measuring the completion time and assessing their hand cleanliness. RESULTS: The computer-assisted teaching program improved the handwashing performance and learning motivation of the subjects. The study group appeared to outperform the control group. Observations reflected that the subjects were highly motivated to learn handwashing with the computerized teaching station. CONCLUSION: The proposed method has the potential to facilitate the teaching and learning of handwashing skills for children with ID. PMID- 22324883 TI - A model of osteoblast-osteocyte kinetics in the development of secondary osteons in rabbits. AB - The kinetics of osteogenic cells within secondary osteons have been examined within a 2-D model. The linear osteoblast density of the osteons and the osteocyte lacunae density were compared with other endosteal lamellar systems of different geometries. The cell density was significantly greater in the endosteal appositional zone and was always flatter than the central osteonal canals. Fully structured osteons compared with early structuring (cutting cones) did not show any significant differences in density. The osteoblast density may remain constant because some of them leave the row and become embedded within matrix. The overall shape of the Haversian system represented a geometrical restraint and it was thought to be related to osteoblast-osteocyte transformation. To test this hypothesis of an early differentiation and recruitment of the osteoblast pool which completes the lamellar structure of the osteon, the number and density of osteoblasts and osteocyte lacunae were evaluated. In the central canal area, the mean osteoblast linear density and the osteocyte lacunae planar density were not significantly different among sub-classes (with the exclusion of the osteocyte lacunae of the 300-1000 MUm(2) sub-class). The mean number of osteoblasts compared with osteocyte lacunae resulted in significantly higher numbers in the two sub-classes, no significant difference was seen in the two middle sub-classes with the larger canals, and there were significantly lower levels in the smallest central canal sub-class. The TUNEL technique was used to identify the morphological features of apoptosis within osteoblasts. It was found that apoptosis occurred during the late phase of osteon formation but not in osteocytes. This suggests a regulatory role of apoptosis in balancing the osteoblast-osteocyte equilibrium within secondary osteon development. The position of the osteocytic lacunae did not correlate with the lamellar pattern and the lacunae density in osteonal radial sectors was not significantly different. These findings support the hypothesis of an early differentiation of the osteoblast pool and the independence of the fibrillar lamellation from osteoblast-osteocyte transformation. PMID- 22324884 TI - Prediction of early hepatic artery thrombosis by intraoperative color Doppler ultrasound in pediatric segmental liver transplantation. AB - Early hepatic artery thrombosis (eHAT) after transplantation is associated with a high incidence of graft failure and mortality in pediatric segmental liver transplantation (LT). The evaluation of intraoperative color Doppler ultrasound (CD-US) parameters and their sensitivity and specificity for the prediction of eHAT were important. Pediatric segmental LTs were performed in 49 consecutive patients from October 2006 to December 2010 in our hospital. A total of seven patients (14.3%) experienced eHAT (within one month) after LT. The intraoperative hepatic artery (HA) diameter (p = 0.026), hepatic arterial peak systolic velocity (HAPSV) (p = 0.006), and hepatic artery resistance index (HARI) (p = 0.000) had significant difference between eHAT group and non-eHAT group. Taking a HA diameter <2 mm, a HAPSV of <40 cm/s and a HARI of <0.6 as threshold to predict eHAT, the sensitivity and specificity were 85.7%, 85.7%, 85.7%, and 61.9%, 76.2%, 88.1%, respectively. A HARI of <0.6 was shown to be the most sensitive and specific single parameter for predicting eHAT. PMID- 22324885 TI - Rubisco activity is associated with photosynthetic thermotolerance in a wild rice (Oryza meridionalis). AB - Oryza meridionalis is a wild species of rice, endemic to tropical Australia. It shares a significant genome homology with the common domesticated rice Oryza sativa. Exploiting the fact that the two species are highly related but O. meridionalis has superior heat tolerance, experiments were undertaken to identify the impact of temperature on key events in photosynthesis. At an ambient CO(2) partial pressure of 38 Pa and irradiance of 1500 umol quanta m(-2) s(-1), the temperature optimum of photosynthesis was 33.7 +/- 0.8 degrees C for O. meridionalis, significantly higher than the 30.6 +/- 0.7 degrees C temperature optimum of O. sativa. To understand the basis for this difference, we measured gas exchange and rubisco activation state between 20 and 42 degrees C and modeled the response to determine the rate-limiting steps of photosynthesis. The temperature response of light respiration (R(light)) and the CO(2) compensation point in the absence of respiration (Gamma(*)) were determined and found to be similar for the two species. C3 photosynthesis modeling showed that despite the difference in susceptibility to high temperature, both species had a similar temperature-dependent limitation to photosynthesis. Both rice species were limited by ribulose-1,5-bisphosphate (RuBP) regeneration at temperatures of 25 and 30 degrees C but became RuBP carboxylation limited at 35 and 40 degrees C. The activation state of rubisco in O. meridionalis was more stable at higher temperatures, explaining its greater heat tolerance compared with O. sativa. PMID- 22324886 TI - Chemometric and multivariate statistical analysis of time-of-flight secondary ion mass spectrometry spectra from complex Cu-Fe sulfides. AB - Time-of-flight secondary ion mass spectrometry (TOF-SIMS) spectra of mineral samples are complex, comprised of large mass ranges and many peaks. Consequently, characterization and classification analysis of these systems is challenging. In this study, different chemometric and statistical data evaluation methods, based on monolayer sensitive TOF-SIMS data, have been tested for the characterization and classification of copper-iron sulfide minerals (chalcopyrite, chalcocite, bornite, and pyrite) at different flotation pulp conditions (feed, conditioned feed, and Eh modified). The complex mass spectral data sets were analyzed using the following chemometric and statistical techniques: principal component analysis (PCA); principal component-discriminant functional analysis (PC-DFA); soft independent modeling of class analogy (SIMCA); and k-Nearest Neighbor (k-NN) classification. PCA was found to be an important first step in multivariate analysis, providing insight into both the relative grouping of samples and the elemental/molecular basis for those groupings. For samples exposed to oxidative conditions (at Eh ~430 mV), each technique (PCA, PC-DFA, SIMCA, and k-NN) was found to produce excellent classification. For samples at reductive conditions (at Eh ~ -200 mV SHE), k-NN and SIMCA produced the most accurate classification. Phase identification of particles that contain the same elements but a different crystal structure in a mixed multimetal mineral system has been achieved. PMID- 22324887 TI - Single-molecule, single-particle approaches for exploring the structure and kinetics of nanocatalysts. AB - In this Article, we focus on the in situ observation of photochemical reactions on individual nanoobjects of solid catalysts using single-molecule, single particle fluorescence spectroscopy. The use of high-resolution imaging techniques with suitable fluorogenic probes enables us to determine the location of the catalytically active sites that are related to the structural heterogeneities on the surface of the solid catalyst and the temporal fluctuation of photochemical reactivity. Furthermore, we present the real-time observation of metastable gold nanoclusters in polymer matrices at the single-cluster level. This Article encourages readers to explore the nanoworld in terms of practical applications in many fields such as fundamental physics and chemistry. PMID- 22324888 TI - Evaluation of the impedance analyzer PocH-100iV Diff for analysis of canine and feline blood. AB - BACKGROUND: An automated impedance-based in-house hematology analyzer, the PocH 100iV Diff, which provides a 3-part leukocyte differential count that includes eosinophils, recently has been introduced. OBJECTIVES: The aims of this study were to validate results from the PocH-100iV Diff for dogs and cats and evaluate the impact of the anticoagulant used and sample storage conditions. METHODS: Blood samples collected in K(3) EDTA from 153 cats and 150 dogs were included in the comparison study. The reference analyzer was the ADVIA 2120 hematology analyzer, and manual differential leukocyte counts and PCV were the manual reference methods. RESULTS: Coefficients of variation were < 3% except for platelet counts and feline differential and eosinophil counts. Correlation between analyzers was good to excellent except for hemoglobin (HGB) concentration in dogs and RBC indices for both species. Biases were close to 0 except for MCHC and platelet counts. Correlation with manual counts was good for lymphocytes and OTHR cells (combined neutrophil and monocyte counts) and fair and poor for feline and canine eosinophil counts, respectively. Estimated sensitivity and specificity for detection of eosinophilia were, respectively, 50% and 98% for cats and 34% and 77% for dogs. A significant anticoagulant effect was seen for MCV in cats and for HCT, MCH, MCHC, and platelet, OTHR, and eosinophil counts in dogs. RBC and WBC counts, HGB concentration, and MCH were stable for 72 h. HCT, MCV, MCHC, and platelet counts were affected by sample storage (dogs > cats; 22 degrees C > 4 degrees C). CONCLUSIONS: The PocH-100iV Diff is a suitable in-house instrument. A strength is its specific, but moderately sensitive, detection of feline eosinophils. PMID- 22324889 TI - Explants of intact endometrium to model bovine innate immunity and inflammation ex vivo. AB - PROBLEM: Bacterial infections commonly cause bovine endometritis and infertility via innate immune pathways. However, mechanistic studies using isolated cells or chopped tissue may be compromised by the disruption of endometrial architecture and release of damage-associated molecular patterns. So, this study aimed to establish an ex vivo model of intact bovine endometrium to study innate immunity and inflammation. METHOD OF STUDY: Intact bovine endometrium explants were collected using a sterile 8-mm punch biopsy and cultured ex vivo with bacteria or pathogen-associated molecules. Interleukin accumulation was measured, and tissue viability was assessed by microscopy, TdT-mediated biotin-dUTP nick-end labelling and lactate dehydrogenase assay. RESULTS: Intact endometrium explants accumulated IL-6, IL-1beta and IL-8 in response to Gram-negative or Gram-positive bacteria, and their purified pathogen-associated molecules; inflammatory responses were dependent on the stage of oestrous cycle. Explants of intact endometrium maintained viability and tissue architecture, and had lower basal accumulation of interleukins compared with explants using chopped endometrium. CONCLUSION: This study established a tractable ex vivo model of intact endometrium to explore the mechanisms of immunity and inflammation in the bovine endometrium. PMID- 22324890 TI - The Shikani optical stylet as an alternative to the GlideScope(r) videolaryngoscope in simulated difficult intubations--a randomised controlled trial. AB - The GlideScope((r)) videolaryngoscope is widely utilised in the management of the difficult airway. However, complications such as mucosal injury, palatal and tonsillar perforations have been reported with its use. The Shikani optical stylet has shown promise in aiding difficult intubations. This randomised controlled trial evaluates the Shikani optical stylet as an alternative to the GlideScope videolaryngoscope in patients undergoing anaesthesia, with a simulated difficult airway. Sixty patients were randomised to undergo tracheal intubation with either the GlideScope videolaryngoscope (n = 30) or the Shikani optical stylet (n = 30). All patients had rigid cervical collars applied to simulate a difficult airway. Tracheal intubation was successful in all patients, with first attempt success rates of 97% (29/30) the GlideScope group compared with 93% (28/30) in the Shikani group compared with 93% (28/30) in the Shikani group (p = 0.5). The mean (SD) time to intubation was 64 (37) s when using the GlideScope and 58 (26) s in the Shikani group (p = 0.48). A higher incidence of airway mucosal injury was noted in patients intubated with the GlideScope videolaryngoscope, compared with the Shikani optical stylet (5 vs 0, respectively, p = 0.05). This trial suggests that the Shikani optical stylet is a viable alternative to the GlideScope videolaryngoscope in the management of the difficult airway. PMID- 22324891 TI - Continuous electrical tuning of the chemical composition of TaO(x)-based memristors. AB - TaO(x)-based memristors have recently demonstrated both subnanosecond resistance switching speeds and very high write/erase switching endurance. Here we show that the physical state variable that enables these properties is the oxygen concentration in a conduction channel, based on the measurement of the thermal coefficient of resistance of different TaO(x) memristor states and a set of reference Ta-O films of known composition. The continuous electrical tunability of the oxygen concentration in the channel, with a resolution of a few percent, was demonstrated by controlling the write currents with a one transistor-one memristor (1T1M) circuit. This study demonstrates that solid-state chemical kinetics is important for the determination of the electrical characteristics of this relatively new class of device. PMID- 22324892 TI - Impaired learning and memory performance in a subclinical hypothyroidism rat model induced by hemi-thyroid electrocauterisation. AB - It is well known that clinical hypothyroidism (CH) can induce cognitive deficits, and the decision to start treatment for CH with thyroxine is usually straightforward. However, the relationship of cognition dysfunction with subclinical hypothyroidism (SCH) is inconsistent, and the decision concerning the need to treat SCH is controversial. In the present study, we induced a SCH rat model by hemi-thyroid electrocauterisation; then employed a serial of behavioural tests, including a beam balance, open field task and Morris water maze (MWM), to investigate the behaviour performance of SCH rats; and finally explored the protein expression of phosphorylated extracellular signal-regulated kinase (ERK)1/2 in the hippocampus by western blotting. The results demonstrated that hemi-thyroid electrocauterised rats had an elevated plasma thyrotrophin stimulating hormone (TSH) level, with normal free thyroxine (fT4) and triiodothyronine (T3) concentrations, which defines SCH in humans. If rat SCH is diagnosed according to measurements of both plasma TSH higher than 97.5 percentile for the sham group and fT4 in the range 2.5-97.5 percentile for the sham group, the success rate of SCH modelling was 66.6%. SCH decreased exploratory behaviour but did not affect motor function in rats, showing a negative correlation of exploratory behaviour with plasma TSH concentration. Moreover, SCH rats displayed an impairment of learning and memory ability in the MWM task, with a longer escape latency in the acquisition phase and a shorter duration in the target quadrant in the test phase compared to that of sham rats. The mechanism for this might be related to the increased plasma TSH concentration, the decreased hippocampal T3 level and the enhanced expression of phosphorylated ERK1/2 in the hippocampus. The results of the present study, together with the results obtained in other studies, suggest that treatment is necessary for SCH. PMID- 22324893 TI - The first edition of Ocular Immunologyand Inflammation for 2012. PMID- 22324894 TI - Drug-induced inflammation in patients on TNFalpha inhibitors. PMID- 22324895 TI - Controversies in Behcet disease. AB - Behcet disease (BD) is a common, complex, and severely debilitating systemic vasculitis. Despite an increasing understanding of BD overall, there remain many critical questions to be addressed in terms of the epidemiology, pathophysiology, and treatment of this condition. The opinions of uveitis experts related to these issues were recently surveyed and are summarized herein. The survey results revealed significant disparities between responders in terms of important concepts regarding the clinical features, diagnosis, and treatment of this important inflammatory eye disease. PMID- 22324896 TI - Behcet uveitis in the American midwest. AB - PURPOSE: Behcet disease is most common in Asia, the Middle East, and North Africa (Silk Road). The authors compare clinical presentation and course of Behcet uveitis in patients of Silk Road and non-Silk Road descent. METHODS: Retrospective review of patients evaluated at the University of Illinois January 1983-July 2010. RESULTS: Of 6134 new uveitis patients, 36 with available medical records met diagnostic criteria for Behcet disease. Ten (28%) were of Silk Road origin. Retinal vasculitis was the most common ocular manifestation, followed by panuveitis and retinitis. Ocular and systemic manifestations were similar between groups. Seventy-eight percent were treated with systemic immunosuppression, which reduced inflammatory attack rate. CONCLUSIONS: Behcet disease is uncommon in the midwestern United States. Three-quarters of patients in this series were not of Silk Road descent. Physicians should consider the diagnosis of Behcet disease in any patient with retinal vasculitis or uveitis regardless of ethnicity. PMID- 22324897 TI - Infliximab and adalimumab for uveitis. AB - PURPOSE: To describe the corticosteroid-sparing success in controlling chronic uveitis in patients treated with TNFalpha inhibitors. METHODS: Retrospective longitudinal case series of patients started on infliximab (n = 31) or adalimumab (n = 12) for chronic noninfectious uveitis at a tertiary referral center. The main outcome was corticosteroid-sparing success. Secondary outcomes were sustained control of inflammation regardless of corticosteroid-sparing effect, tapering of concurrent nonbiologic therapy, and discontinuation. RESULTS: Sustained control of inflammation with corticosteroid-sparing success on infliximab and adalimumab, respectively, was achieved in 33.3 and 37.5% at 3 months, 60.7 and 62.5% at 6 months, and 60.9 and 57.1% at 12 months. Median time to this outcome was 98 days for infliximab and 169 days for adalimumab. Six infliximab patients had adverse reactions. CONCLUSIONS: Infliximab and adalimumab improve control of ocular inflammation and are successful corticosteroid-sparing agents. However, time to corticosteroid-sparing control of inflammation may take a few months with either agent, and adverse reactions may limit treatment. PMID- 22324899 TI - Anterior uveitis after treatment of hepatitis C with alpha interferon: the recurrence of a previous inflammatory process due to presumed ocular toxocariasis. AB - OBJECTIVE: To report a case of recurrent unilateral presumed ocular toxocariasis after treatment of hepatitis C. DESIGN: Case study. METHODS: Clinical findings, ultrasonography, computed tomography, and serological tests were performed. Once diagnosis was made, effective treatment was administered. RESULTS: A 46-year-old woman with a long history of decreased unilateral visual acuity presented with anterior uveitis after the use of interferon alpha and ribavirin for treatment of hepatitis C. A biomicroscopic examination revealed active anterior uveitis, with ultrasonography and computed tomography demonstrating a central granuloma due to partially calcified toxocariasis. After treatment with corticosteroids and cycloplegics, the symptoms were alleviated. CONCLUSION: immunostimulation could cause a relapse of the inflammatory reaction found in uveitis due to toxocariasis. PMID- 22324898 TI - Genetics of immunological and inflammatory components in age-related macular degeneration. AB - Age-related macular degeneration (AMD), affecting 30 to 50 million elder individuals worldwide, is a disease affecting the macular retina and choroid that can lead to irreversible central vision loss and blindness. Recent findings support a role for immunologic processes in AMD pathogenesis, including generation of inflammatory related molecules in the Bruch's membrane, recruitment of macrophages, complement activation, microglial activation and accumulation in the macular lesions. Pro-inflammatory effects of chronic inflammation and oxidative stress can result in abnormal retinal pigment epithelium, photoreceptor atrophy and choroidal neovascularization. The associations of immunological and inflammatory genes, in particular the genes related to innate immunity with AMD support the involvement of various immunological pathways in the AMD pathogenesis. We review the literature on the involvements of inflammatory genes in AMD, highlight recent genetic discoveries, and discuss the potential application of such knowledge in the management of patients with AMD. PMID- 22324900 TI - Intraocular cysticercosis. PMID- 22324901 TI - Interstellar H3+ and HCS+ ions produced in the dissociative photoionization process of CH3C(O)SCH3 in the proximity of the sulfur 2p, carbon 1s, and oxygen 1s edges. AB - In this work we present a study of the dissociative photoionization of S-methyl thioacetate [CH(3)C(O)SCH(3)] by using multicoincidence time-of-flight mass spectrometry and synchrotron radiation in the S 2p, C 1s, and O 1s edges. Total and partial ion yield spectra together with photoelectron-photoion coincidence (PEPICO) and photoelectron-photoion-photoion coincidence (PEPIPICO) spectra were measured. Fragmentation patterns deduced from PEPICO and PEPIPICO spectra at the various excitation energies show a moderate site-specific fragmentation. The dissociation dynamic for the main ion-pair production is discussed. Two-, three-, and four-body dissociation channels have been observed in the PEPIPICO spectra, and the dissociation mechanisms are proposed. The interstellar HCS(+) and H(3)(+) ions can be observed during the synchrotron experiments reported in the present work. PMID- 22324902 TI - A multifunctional envelope-type nanodevice for use in nanomedicine: concept and applications. AB - In the 21st century, drug development has shifted toward larger molecules such as proteins and nucleic acids, which require the use of new chemical strategies. In this process, the drug delivery system plays a central role and intracellular targeting using nanotechnology has become a key technology for the development of successful new medicines. We have developed a new delivery system, a multifunctional envelope-type nanodevice (MEND) based on "Programmed Packaging." In this new concept of packaging, multifunctional nanodevices are integrated into a nanocarrier system according to a program designed to overcome all barriers during the course of biodistribution and intracellular trafficking. In this Account, we introduce our method for delivering nucleic acids or proteins to intracellular sites of action such as the cytosol, nucleus, and mitochondria and for targeting selective tissues in vivo via systemic administration of the nanodevices. First, we introduce an octaarginine-modified MEND (R8-MEND) as an efficient intracellular delivery system, designed especially for vaccinations and transgene expression. Many types of cells can internalize the R8-MEND, mainly by inducing macropinocytosis, and the MEND escapes from macropinosomes via membrane fusion, which leads to efficient antigen presentation via the major histocompatibility complex I pathway in antigen-presenting cells. In addition, the transfection activities of the R8-MEND in dividing cells, such as HeLa or A549 cells, are as high as those for adenovirus. However, because the R8-MEND cannot induce sufficient transgene activity in primary cultured dendritic cells, which are critical regulators of the immune response, we converted the R8-MEND into a tetralamellar MEND (T-MEND). The T-MEND uses a new packaging method and delivers condensed pDNA into the nucleus via fusion between the envelopes and the nuclear membrane. To achieve efficient transfection activity, we also optimized the decondensation of nucleic acids within the nucleus. To optimize mitochondrial drug delivery, we introduced the MITOPorter. Many types of materials can be packaged into this liposome-based nanocarrier and then delivered to mitochondria via membrane fusion mechanisms. Finally, we describe an integrated strategy for in vivo tumor delivery and optimization of intracellular trafficking. Successful tumor delivery typically requires coating the surfaces of nanoparticles with PEG, but PEG can also limit uptake by the reticuloendothelial system and reduce the efficiency of intracellular trafficking. Here we integrate the optimum biodistribution and intracellular trafficking of the MEND with an innovative strategy such as enzymatically cleavable PEG and a short membrane peptide, GALA. Some of these strategies will soon be tested in the clinic. PMID- 22324903 TI - Hitting a complex target: an update on interleukin-6 trans-signalling. AB - INTRODUCTION: Interleukin-6 (IL-6) is a key target in inflammation and cancer. Selective inhibition of IL-6 trans-signalling could provide the same or even higher therapeutic efficacy with a better side effect profile than complete IL-6 inhibition. Animal studies with IL-6 inhibitors show that the classic IL-6 signalling pathway via the membrane-bound IL-6 receptor (IL-6R) has important physiological functions, whereas blocking the trans-signalling pathway via the soluble IL-6R (sIL-6R) is sufficient to prevent or treat IL-6-driven diseases. Due to the success of the anti-IL-6R antibody tocilizumab and difficulties of constructing selective trans-signalling inhibitors, most drug candidates in clinical development target IL-6 or IL-6R and, thus, both IL-6 pathways. By contrast, the fusion protein sgp130Fc selectively targets IL-6/sIL-6R trans signalling by utilising the soluble gp130 receptor as the natural inhibitor of trans-signalling. AREAS COVERED: The authors summarise recent developments in the field with a focus on animal studies highlighting the mechanistic differences between classic and trans-signalling and their therapeutic implications. EXPERT OPINION: Characterising disease mechanisms in terms of the employed IL-6 pathways will help to select the right therapeutic IL-6 inhibitor in the future. The trans signalling inhibitor sgp130Fc is about to enter the clinic and holds promise for a clinically different profile in comparison with complete IL-6 inhibitors. PMID- 22324904 TI - Zooming-in on floral nectar: a first exploration of nectar-associated bacteria in wild plant communities. AB - Floral nectar of some animal-pollinated plants usually harbours highly adapted yeast communities which can profoundly alter nectar characteristics and, therefore, potentially have significant impacts on plant reproduction through their effects on insect foraging behaviour. Bacteria have also been occasionally observed in floral nectar, but their prevalence, phylogenetic diversity and ecological role within plant-pollinator-yeast systems remains unclear. Here we present the first reported survey of bacteria in floral nectar from a natural plant community. Culturable bacteria occurring in a total of 71 nectar samples collected from 27 South African plant species were isolated and identified by 16S rRNA gene sequencing. Rarefaction-based analyses were used to assess operational taxonomic units (OTUs) richness at the plant community level using nectar drops as sampling units. Our results showed that bacteria are common inhabitants of floral nectar of South African plants (53.5% of samples yielded growth), and their communities are characterized by low species richness (18 OTUs at a 16S rRNA gene sequence dissimilarity cut-off of 3%) and moderate phylogenetic diversity, with most isolates belonging to the Gammaproteobacteria. Furthermore, isolates showed osmotolerance, catalase activity and the ability to grow under microaerobiosis, three traits that might help bacteria to overcome important factors limiting their survival and/or growth in nectar. PMID- 22324905 TI - A new selective liquid membrane extraction method for the determination of basic herbicides in agro-processed fruit juices and Ethiopian honey wine (Tej) samples. AB - Supported liquid membrane (SLM) extraction was optimised for trace extraction and enrichment of selected triazine herbicides from a variety of agro-processed fruit juices and Ethiopian honey wine (Tej) samples. In the extraction process, a 1:1 mixture of n-undecane and di-n-hexylether was immobilised in a thin porous PTFE membrane that forms a barrier between two aqueous phases (the donor and acceptor phases) in a flow system. The extracts constitute the selectively enriched analytes collected from the acceptor phase and were analysed by transferring to a HPLC-UV system using a diode array detector at 235 nm. High enrichment factors were obtained with very good repeatability of results, and the detection limit was lower than 3.00 ug l-1 for ametryn in apple juice. The optimised method showed very good linearity of over 50-500 ug l-1 with a correlation coefficient of >0.990 or better for triplicate analysis. All chromatograms gave well resolved peaks with no interfering peaks at the retention times of the selected triazines, showing high selectivity of the SLM extraction method in combination with HPLC-UV for the selected matrices. The optimised method can be used as an alternative solventless extraction method for microgram-level extraction of other triazine herbicides and a variety of pesticides from liquid and semi-liquid environmental, biological and food matrices. PMID- 22324906 TI - Human T-lymphotropic virus type 1 and type 2 seroprevalence, incidence, and residual transfusion risk among blood donors in Brazil during 2007-2009. AB - Human T-lymphotropic virus type 1/2 (HTLV-1/2) infection is endemic in Brazil but representative donor prevalence and incidence data are lacking. All blood donations (2007-2009) from three blood centers in Brazil were studied. Samples reactive on one HTLV screening test (EIA) were retested with a different EIA; dual EIA reactivity correlated strongly with a confirmatory Western blot. Prevalence, incidence, and residual transfusion risk were calculated. Among 281,760 first-time donors, 363 were positive for HTLV on both EIAs (135 per 10(5), 95% CI 122-150). Prevalence differed considerably by region, from 83 to 222 per 10(5). Overall incidence rate was 3.6/10(5) person-years and residual transfusion risk was 5.0/10(6) per blood unit transfused. The logistic regression model showed significant associations with: age [adjusted odds ratio (aOR)=5.23 for age 50+ vs. <20], female sex (aOR=1.97), black (aOR=2.70 vs. white), and mixed skin colors (aOR=1.78 vs. white), and inversely with education (aOR=0.49, college vs. less than high school). HTLV testing with a dual-EIA strategy is feasible and can be useful in areas with low resources. Incidence and residual risk of HTLV-1 transmission by transfusion were relatively high and could be reduced by improving donor recruitment and selection in high prevalence areas. Blood center data may contribute to surveillance for HTLV infection. PMID- 22324907 TI - Effects to exposure of tobacco smoke and alcohol on the tongue and pharynx of rats. AB - AIM: To study in rats the effects of exposure to tobacco and alcohol on the mucosa of the tongue and pharynx. MATERIAL AND METHODS: Forty adult Wistar rats were allocated into four groups of 10 animals each: GI (control), food and water "ad libitum"; GII (alcohol), 30% of ethanol diluted in drinking water and food "ad libitum"; GIII (tobacco), exposure to the smoke of 10 cigarettes/day, food and water "ad libitum"; GIV (alcohol and tobacco), simultaneous exposure to both agents. After 260 days, the animals were sacrificed. Tongue and pharynx were removed for histopathological analysis. RESULTS: GI had the lowest tongue and pharynx histological scores. In GII, GIII, and GIV tongue samples revealed: apical cell hyperplasia (GII: 60%, GIII: 30%, GIV: 20%), basal cell hyperplasia (GII: 60%, GIII: 40%), hyperkeratosis (GII: 70%, GIII: 30%, GIV: 30%), dysplasia (GII: 60%, GIII: 60%, GIV: 50%), and apoptosis (GII: 60%, GIII: 40%, GIV: 60%). Pharynx samples revealed: apical cell hyperplasia (GII: 40%, GIII: 30%, GIV: 70%), basal cell hyperplasia (GII: 30%, GIII: 40%, GIV: 40%), hyperkeratosis (GII: 50%, GIII: 80%, GIV: 40%), and dysplasia (GII: 50%, GIII: 80%, GIV: 50%). Carcinoma in situ was detected in both sites. CONCLUSIONS: Alcohol and tobacco led to significant tongue and pharyngeal lesions that ranged from benign events to severe dysplasia. These findings confirm the deleterious effects of alcohol and tobacco on the airway mucosa. PMID- 22324908 TI - Activity, polypeptide and gene identification of thylakoid Ndh complex in trees: potential physiological relevance of fluorescence assays. AB - Three evergreen (Laurus nobilis, Viburnum tinus and Thuja plicata) and two autumnal abscission deciduous trees (Cydonia oblonga and Prunus domestica) have been investigated for the presence (zymogram and immunodetection) and functionality (post-illumination chlorophyll fluorescence) of the thylakoid Ndh complex. The presence of encoding ndh genes has also been investigated in T. plicata. Western assays allowed tentative identification of zymogram NADH dehydrogenase bands corresponding to the Ndh complex after native electrophoresis of solubilized fractions from L. nobilis, V. tinus, C. oblonga and P. domestica leaves, but not in those of T. plicata. However, Ndh subunits were detected after SDS-PAGE of thylakoid solubilized proteins of T. plicata. The leaves of the five plants showed the post-illumination chlorophyll fluorescence increase dependent on the presence of active Ndh complex. The fluorescence increase was higher in autumn in deciduous, but not in evergreen trees, which suggests that the thylakoid Ndh complex could be involved in autumnal leaf senescence. Two ndhB genes were sequenced from T. plicata that differ at the 350 bp 3' end sequence. Comparison with the mRNA revealed that ndhB genes have a 707-bp type II intron between exons 1 (723 bp) and 2 (729 bp) and that the UCA 259th codon is edited to UUA in mRNA. Phylogenetically, the ndhB genes of T. plicata group close to those of Metasequoia, Cryptomeria, Taxodium, Juniperus and Widdringtonia in the cupresaceae branch and are 5' end shortened by 18 codons with respect to that of angiosperms. PMID- 22324909 TI - The experiences of parents of children with severe autism in connection with their children's anaesthetics, in the presence and absence of the perioperative dialogue: a hermeneutic study. AB - The aim of this study was to obtain an understanding of what parents of children with severe autism experience in connection with their child's anaesthetics, in the presence and absence of the perioperative dialogue. Twelve parents who had experience of their child receiving anaesthetics on one or more occasions took part in this study, in which anaesthesia care was organized as a perioperative dialogue. Data were collected by means of conversational interviews, and the text was interpreted using a hermeneutic approach. The hermeneutic text interpretation led to a new understanding based on the knowledge that in the absence of the perioperative dialogue, previous anaesthetics had meant the suffering of care by the following: a hopeless struggle, unspeakable suffering and a disgraceful scenario. However, continuity in the perioperative dialogue provided to be a way out of the suffering by being received by warm hands, being received by a known face and a subtle interplay between the child and nurse. Although health and well being may be unobtainable goals in this special context of care, the findings provided ample descriptions of the positive effects of the perioperative dialogue, which is all the more valuable when dealing with children who will need repeated anaesthetics in the future. PMID- 22324910 TI - Examining the safety of amiodarone. AB - INTRODUCTION: Amiodarone is the most widely used antiarrhythmic agent, with demonstrated effectiveness against all the spectrum of cardiac tachyarrhythmias. The risk of adverse effects acts as a limiting factor to its utilization especially in the long term. This article systematically reviews the published evidence on amiodarone versus placebo to examine its safety as an antiarrhythmic drug. AREAS COVERED: Authors collected data on adverse effects reported in 49 randomized placebo-controlled trials with amiodarone. Adverse effects were classified according to the organ/system involved. Pooled estimates of the number needed to treat (NNT) and to harm (NNH) versus placebo were calculated. EXPERT OPINION: Amiodarone is effective for both the acute conversion of atrial fibrillation (AF) (11 trials, NNT = 4 at 24 h; p = 0.003) and the prevention of postoperative AF (18 trials, NNT = 8; p < 0.001), although with an increased risk of bradycardia, hypotension, nausea or phlebitis (pooled NNH = 4; p < 0.001). Amiodarone administration for the maintenance of sinus rhythm has a favorable net clinical benefit (pooled NNT = 3; p < 0.001 versus pooled NNH for either thyroid toxicity, gastrointestinal discomfort, skin toxicity or eye toxicity = 11; p < 0.001). Treatment with amiodarone for the prophylaxis of sudden cardiac death has less favorable net clinical benefit (15 trials, NNT = 38; p < 0.001 versus NNH for either thyroid toxicity, hepatic toxicity, pulmonary toxicity or bradycardia = 14; p < 0.001). Amiodarone treatment in this setting should be used in only selected cases. PMID- 22324911 TI - Diruthenium(III,III) bis(alkynyl) compounds with donor/acceptor-substituted geminal-diethynylethene ligands. AB - Reported in this contribution are the preparation and characterization of a series of Ru(2)(DMBA)(4) (DMBA = N,N'-dimethylbenzamidinate) bis(alkynyl) compounds, trans-Ru(2)(DMBA)(4)(X-gem-DEE)(2) [gem-DEE = sigma-geminal diethynylethene; X = H (1), Si(i)Pr(3) (2), Fc (3); 4-C(6)H(4)NO(2) (4), and 4 C(6)H(4)NMe(2) (5)]. Compounds 1-5 were characterized by spectroscopic and voltammetric techniques as well as the single-crystal X-ray diffraction studies of 2 and 3. Both the single-crystal structural data of compounds 2 and 3 and the spectroscopic/voltammetric data indicate that the gem-DEE ligands are similar to simple acetylides in their impact on the molecular and electronic structures of the Ru(2)(DMBA)(4) core. Furthermore, density functional theory calculations revealed more extensive pi delocalization in aryl-donor-substituted gem-DEEs and that the hole-transfer mechanism will likely dominate the charge delocalization in Ru(2)-gem-DEE-based wires. PMID- 22324912 TI - Factors related to immunosuppressant medication adherence in renal transplant recipients. AB - Non-adherence to immunosuppressant medications (ISM) is a significant issue for transplant recipients. This study examines factors influencing ISM adherence in renal transplant recipients (RTRs). Patient-reported data were collected through a cross-sectional survey including use of ISMs, adherence behaviors, perceived adherence barriers, beliefs and attitudes toward ISMs, and patient life satisfaction. Logistic regression was conducted to examine how RTRs' beliefs about use of ISMs, life satisfaction, and ISM adherence barriers were related to adherence. A total of 512 adult commercial insurance enrollees following renal transplantation were included in the analysis. One hundred and seventy-seven RTRs were non-adherent (34.5%); the most frequently cited reason was forgetfulness. RTRs aged 18-29 yr were more likely to be non-adherent than recipients 46-64 yr old (p <= 0.001). Non-adherent RTRs had greater adherence barriers than adherent RTRs (p < 0.001). Adherent RTRs believed their ISMs were more necessary than non adherent RTRs (p < 0.001), while non-adherent RTRs had greater concerns about taking ISMs (p = 0.009) and believed they had less control over their lives than adherent RTRs (p < 0.001). Non-adherent RTRs had lower life satisfaction (p < 0.001). Non-adherence is significantly associated with patients' beliefs about ISMs, perceived barriers, and lower life satisfaction. Strategies to increase ISM adherence are discussed. PMID- 22324913 TI - Stereoselective synthesis of both tetrahydropyran rings of the antitumor macrolide, (-)-lasonolide A. AB - Stereoselective syntheses of both functionalized tetrahydropyran subunits of (-) lasonolide A are described. These tetrahydropyran rings were constructed using catalytic asymmetric hetero Diels-Alder reactions as the key steps. The C22 quaternary stereocenter present in the upper tetrahydropyran ring was constructed by a stereoselective alkylation, and the C9 hydroxy stereochemistry of the bottom tetrahydropyran was constructed by a stereoselective epoxidation followed by a regioselective epoxide opening reaction. PMID- 22324914 TI - Essential cysteine residues for human RNase kappa catalytic activity. AB - Human RNase kappa is an endoribonuclease expressed in almost all tissues and organs and belongs to a highly conserved protein family bearing representatives in all metazoans. To gain insight into the role of cysteine residues in the enzyme activity or structure, a recombinant active form of human RNase kappa expressed in Pichia pastoris was treated with alkylating agents and dithiothreitol (DTT). Our results showed that the human enzyme is inactivated by DDT, while it remains fully active in the presence of alkylating agents. The unreduced recombinant protein migrates on SDS/PAGE faster than the reduced form. This observation in combination with the above findings indicated that human RNase kappa does not form homodimers through disulfide bridges, and cysteine residues are not implicated in RNA catalysis but participate in the formation of intramolecular disulfide bond(s) essential for its ribonucleolytic activity. The role of the cysteine residues was further investigated by expression and study of Cys variants. Ribonucleolytic activity experiments and SDS/PAGE analysis of the wild-type and mutant proteins under reducing and non-reducing conditions demonstrated that Cys7, Cys14 and Cys85 are not essential for RNase activity. On the other hand, replacement of Cys6 or Cys69 with serine led to a complete loss of catalytic activity, indicating the necessity of these residues for maintaining an active conformation of human RNase kappa by forming a disulfide bond. Due to the absolute conservation of these cysteine residues, the Cys6-Cys69 disulfide bond is likely to exist in all RNase kappa family members. PMID- 22324915 TI - Identification of novel S-adenosyl-L-homocysteine hydrolase inhibitors through homology-model-based virtual screening, synthesis, and biological evaluation. AB - The present study describes a successful application of computational approaches to identify novel Leishmania donovani (Ld) AdoHcyase inhibitors utilizing the differences for Ld AdoHcyase NAD(+) binding between human and Ld parasite. The development and validation of the three-dimensional (3D) structures of Ld AdoHcyase using the L. major AdoHcyase as template has been carried out. At the same time, cloning of the Ld AdoHcyase gene from clinical strains, its overexpression and purification have been performed. Further, the model was used in combined docking and molecular dynamics studies to validate the binding site of NAD in Ld. The hierarchical structure based virtual screening followed by the synthesis of five active hits and enzyme inhibition assay has resulted in the identification of novel Ld AdoHcyase inhibitors. The most potent inhibitor, compound 5, may serve as a "lead" for developing more potent Ld AdoHcy hydrolase inhibitors as potential antileishmanial agents. PMID- 22324916 TI - First trimester maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A in pregnancies complicated by diabetes mellitus. AB - OBJECTIVE: To investigate whether markers of first trimester screening for aneuploidies, including fetal nuchal translucency (NT), maternal serum free beta human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein A (PAPP-A), are altered in women with pre-existing type-1 and type-2 diabetes mellitus, and in women that subsequently develop gestational diabetes mellitus (GDM). DESIGN: Retrospective analysis of prospective combined screening for aneuploidies in singleton pregnancies at 11(+0) -13(+6) weeks of gestation. SETTING: Antenatal clinic. POPULATION: Singleton pregnancies at 11(+0) -13(+6) weeks of gestation resulting in the delivery of phenotypically normal neonates. The study included 194 women with type-1 diabetes, 122 women with type-2 diabetes, 779 women who developed GDM and 41,007 non-diabetic controls. METHODS: Maternal free beta-hCG and PAPP-A levels were expressed as multiples of the respective normal median (MoM), and fetal NT was expressed as a difference from the expected median (Delta). MAIN OUTCOME MEASURES: Comparison of median MoM maternal free beta-hCG and PAPP-A, and fetal NT, in the four outcome groups. RESULTS: There were no significant differences between the groups in median DeltaNT and maternal free beta-hCG MoM. Maternal median PAPP-A in type-2 diabetes, compared with the non-diabetic group, was reduced (0.75 MoM, IQR 0.50 1.09 MoM versus 1.00 MoM, IQR 0.68-1.42 MoM; P < 0.001), which resulted in doubling in the false-positive rate in the combined screening in this population. There were no significant differences in maternal PAPP-A between the other groups. CONCLUSIONS: In women with type-2 diabetes, the estimation of accurate patient-specific risk in the first trimester combined screening for aneuploidies necessitates an adjustment of maternal serum PAPP-A. PMID- 22324917 TI - Prediction of selective fetal growth restriction and twin-to-twin transfusion syndrome in monochorionic twins. AB - OBJECTIVE: To study the correlation of discrepancy between crown-rump length (CRL) and nuchal translucency (NT) in monochorionic twins at 11-14 weeks of gestation and subsequent development of twin-to-twin transfusion syndrome (TTTS) and selective fetal growth restriction (sFGR). DESIGN: Retrospective cohort study. SETTING: Tertiary-care Fetal Medicine Unit, London. SAMPLE: Monochorionic twin pregnancies with known outcome. METHODS: Inter-twin discrepancy was calculated as a percentage of the larger CRL and smaller NT and compared among those developing TTTS, those with sFGR and those with normal outcome. Receiver operating characteristic (ROC) curves were constructed to evaluate the performance of inter-twin discrepancy in prediction of sFGR and TTTS. MAIN OUTCOME MEASURES: Development of TTTS and sFGR. RESULTS: A total of 242 monochorionic twin pregnancies were studied (102 TTTS, 36 sFGR and 104 controls). The median CRL discrepancy in the sFGR group (11.9%) was significantly higher (P < 0.001) than in the TTTS group (3.8%) and control group (3.5%). Median inter twin NT discrepancies were not significantly different (P = 0.869) between sFGR and both TTTS and control groups (15.6%, 16.7% and 14.8%, respectively). Discrepancy in CRL performs well as a screening test for sFGR (area under ROC curve = 0.89), but not for TTTS (area under ROC curve = 0.58). CONCLUSIONS: First trimester CRL discrepancy in monochorionic twins is a marker for subsequent development of sFGR rather than TTTS. Inter-twin NT discrepancy does not appear to be significantly different in these two groups from those with normal outcome. PMID- 22324918 TI - Fetal loss in women with hereditary thrombophilic defects and concomitance of other thrombophilic defects: a retrospective family study. AB - OBJECTIVE: To assess the absolute risk of fetal loss associated with hereditary deficiencies of antithrombin (AT), protein C (PC) and protein S (PS), and the contribution of additional thrombophilic defects to this risk. DESIGN: A retrospective family cohort study. SETTING: A tertiary referral teaching hospital. POPULATION: Women from families with hereditary deficiencies of AT, PC and PS, and their non-deficient relatives. METHODS: We assessed the absolute risk of fetal loss, comparing deficient women with non-deficient female relatives. MAIN OUTCOME MEASURES: Early, late and total fetal loss rates; odds ratios of fetal loss. RESULTS: We evaluated 289 women, who had 860 pregnancies. The total fetal loss rates were 23% (AT deficient), 26% (PC deficient), 11% (type-I PS deficient) and 15% (type-III PS deficient), compared with 11, 18, 12 and 13% in non-deficient women, respectively. Odds ratios were 2.3 (95% CI 0.9-6.1), 2.1 (95% CI 0.9-4.7), 0.7 (95% CI 0.2-1.8) and 1.1 (95% CI 0.6-2.0), none of which reached statistical significance. Differences were mainly the result of higher late fetal loss rates in women deficient in AT (OR 11.3, 95% CI 3.0-42.0) and PC (OR 4.7, 95% CI 1.3-17.4). The concomitance of factor-V Leiden and prothrombin G20210A was observed in 19% of women, and did not increase the risk of fetal loss. CONCLUSIONS: Although absolute risks of fetal loss were high, odds ratios of total fetal loss were not statistically significant in deficient versus non deficient women. However the higher absolute risks appeared to reflect higher late fetal loss rates as opposed to early fetal loss rates. An additional effect of concomitance of factor-V Leiden and prothrombin G20210A was not demonstrated, which may result from the exclusion of women at highest risk of venous thromboembolism, or from the small numbers sampled in the study. PMID- 22324919 TI - Dysregulated biomarkers induce distinct pathways in preterm birth. AB - OBJECTIVE: To document racial disparity in biomarker concentrations in maternal/fetal plasma and amniotic fluid between African Americans and European Americans with spontaneous preterm birth (PTB; cases) and normal term birth (controls), and their contribution to distinct pathophysiological pathways of PTB. DESIGN: Nested case-control study. SETTING: The Perinatal Research Center, Nashville, Tennessee, USA. SAMPLE: Maternal and fetal plasma and amniotic fluid samples were collected from 105 cases (59 African American and 46 European American) and 86 controls (40 African American and 46 European American). METHODS: Thirty-six biomarkers were analysed using the protein microarray approach. MAIN OUTCOME MEASURES: Differences in biomarker concentrations between cases and controls of different races in maternal, fetal and intra-amniotic compartments, and the risk of PTB. Dysregulated biomarker-induced PTB pathways associated with PTB in each race were determined using ingenuity pathway analysis (IPA). RESULTS: Racial disparity was observed in biomarker concentrations in each compartment between cases and controls: amniotic fluid, IL8 and MIP1alpha differed between case and controls in European Americans, whereas ANGPT2, Eotaxin, ICAM-1, IL-1beta, IL1RA, RANTES and TNFalpha differed between case and controls in African Americans. In both races the FAS ligand, MCP-3 and TNFR-I differed between cases and controls. For fetal plasma, ANGPT2, Eotaxin, FGF basic, ICAM-1, IGF-I, IL10, IL-1beta, IL2, IP10 KGF, MCP-3, MIP1alpha, PDGF-BB, TGFalpha, TGFbeta1, TIMP1, TNFalpha, TNFR-I, TNFR-II and VEGF differed between cases and controls in European Americans, whereas only MMP7 differed between cases and controls in African Americans. IL-8 differed between cases and controls in both races. For maternal plasma, IL1RA, MMP7 and VEGF differed between cases and controls in European Americans, whereas ANGPT2, FGF basic, IL-1beta, IL5, IL6R, KGF, MCP-3, MIP1alpha, TIMP1 and TNFalpha differed between cases and controls in African Americans. ANG, IL8 and TNFR-I differed between cases and controls in both races. CONCLUSIONS: We conclude that: (1) biomarker concentrations in maternal, fetal and intra-amniotic compartments differ between cases and controls; (2) there is racial disparity in the biomarker profile in each of the compartments; (3) substantial numbers of dysregulated fetal plasma biomarkers contribute to PTB in European Americans, whereas maternal plasma biomarkers contribute to PTB in African Americans; and (4) both inflammation and haematological functions are associated with PTB in European Americans, but maternal proinflammatory changes dominate PTB in African Americans. Biomarker analyses document racial disparity and the distinct pathophysiological contributions from different compartments that can determine pregnancy outcome. PMID- 22324920 TI - Motor vehicle accidents during pregnancy: a population-based study. AB - This population-based cohort study of more than 600,000 Australian women describes the incidence of motor vehicle accidents (MVA) during pregnancy and the immediate and subsequent pregnancy outcomes. In this study, 3.5 women per 1000 maternities were admitted to hospital following an MVA. Immediate delivery was uncommon: 0.4% at <20 weeks of gestation and 3.5% at >= 20 weeks of gestation. Outcomes for those giving birth immediately were poor, with increased risk of antepartum haemorrhage, preterm birth, caesarean section and perinatal death. In contrast, women who remained undelivered following an MVA (96%) had similar pregnancy outcomes to women not involved in MVAs, and can be reassured. PMID- 22324922 TI - Re: Clinical characteristics of well women seeking labial reduction surgery: a prospective study. PMID- 22324923 TI - Re: Missed opportunities for type 2 diabetes testing following gestational diabetes: a population-based cohort study. PMID- 22324925 TI - Prognostic value of human chorionic gonadotropin levels 4 days after a single dose of methotrexate for ectopic pregnancy. PMID- 22324926 TI - Severity of asthma in pregnancy affects perinatal outcomes. PMID- 22324928 TI - Reversed umbilical arterial end diastolic flow, sildenafil treatment and early stillbirths. PMID- 22324933 TI - Novel Haemoproteus species (Haemosporida: Haemoproteidae) from the swallow-tailed gull (Lariidae), with remarks on the host range of hippoboscid-transmitted avian hemoproteids. AB - Haemoproteus (Haemoproteus) jenniae n. sp. (Haemosporida: Haemoproteidae) is described from a Galapagos bird, the swallow-tailed gull Creagrus furcatus (Charadriiformes, Laridae), based on the morphology of its blood stages and segments of the mitochondrial cytochrome b (cyt b) gene. The most distinctive features of H. jenniae development are the circumnuclear gametocytes occupying all cytoplasmic space in infected erythrocytes and the presence of advanced, growing gametocytes in which the pellicle is closely appressed to the erythrocyte envelope but does not extend to the erythrocyte nucleus. This parasite is distinguishable from Haemoproteus larae, which produces similar gametocytes and parasitizes closely related species of Laridae. Haemoproteus jenniae can be distinguished from H. larae primarily due to (1) the predominantly amoeboid outline of young gametocytes, (2) diffuse macrogametocyte nuclei which do not possess distinguishable nucleoli, (3) the consistent size and shape of pigment granules, and (4) the absence of rod-like pigment granules from gametocytes. Additionally, fully-grown gametocytes of H. jenniae cause both the marked hypertrophy of infected erythrocytes in width and the rounding up of the host cells, which is not the case in H. larae. Phylogenetic analyses identified the DNA lineages that are associated with H. jenniae and showed that this parasite is more closely related to the hippoboscid-transmitted (Hippoboscidae) species than to the Culicoides spp.-transmitted (Ceratopogonidae) species of avian hemoproteids. Genetic divergence between morphologically well-differentiated H. jenniae and the hippoboscid-transmitted Haemoproteus iwa, the closely related parasite of frigatebirds (Fregatidae, Pelecaniformes), is only 0.6%; cyt b sequences of these parasites differ only by 1 base pair. This is the first example of such a small genetic difference in the cyt b gene between species of the subgenus Haemoproteus. In a segment of caseinolytic protease C gene (ClpC), genetic divergence is 4% between H. jenniae and H. iwa. This study corroborates the conclusion that hippoboscid-transmitted Haemoproteus parasites infect not only Columbiformes birds but also infect marine birds belonging to Pelecaniformes and Charadriiformes. We conclude that the vertebrate host range should be used cautiously in identification of subgenera of avian Haemoproteus species and that the phylogenies based on the cyt b gene provide evidence for determining the subgeneric position of avian hemoproteids. PMID- 22324934 TI - COX inhibitors for airway inflammation. AB - INTRODUCTION: The cyclooxygenase (COX) enzyme, which is responsible for the production of prostaglandins (PGs), key mediators of inflammation, may have the potential to become an attractive target for anti-inflammatory therapy. COX catalyzes the conversion of arachidonic acid (AA) into PGs, which play a significant role in disease. PGs are lipid mediators of central importance in the regulation of inflammation and smooth muscle tone. Airway-resident inflammatory cells release PGs: PGD2 and PDF2a amplify smooth muscle contraction and airway inflammation. Following its conversion from membrane phospholipids by phospholipase, AA enters the prostanoid pathway via COX, which catalyzes the conversion of AA to PGH2. PGH2 is then converted to biologically active PGs by cell-specific PG synthases. As COX is the rate limiting step in the PG pathway, the regulation of this enzyme is of critical importance in PG production. AREAS COVERED: This review addresses the opportunities and challenges of COX inhibitors as therapeutic targets in airway inflammation. The review covers literature from the past 20 years. EXPERT OPINION: Current literature favors COX inhibitors as potential targets for airway diseases. However, from the information available, it is not clear whether the COX enzyme by itself can serve as a target in drug development for asthma and COPD. Therefore, additional research is required to elucidate the mechanisms of action of COX metabolites before it can be considered as a target. PMID- 22324935 TI - Pathogens in the lower respiratory tract of intensive care unit patients: impact of duration of hospital care and mechanical ventilation. AB - BACKGROUND: Ventilator-associated pneumonia (VAP), the most common hospital acquired infection in intensive care unit (ICU) patients, is caused by bacteria in the lower respiratory tract of mechanically ventilated patients. METHODS: The current study was focused on 443 bacterial isolates from the lower respiratory tract of mechanically ventilated ICU patients (n = 346) in a Swedish University Hospital. Data were obtained from a prospective infection control database covering 9 y (2002-2010). We analysed the correlation between duration of hospital care and mechanical ventilation at the time of sampling on the occurrence of different pathogens. RESULTS: Duration of hospital care and mechanical ventilation prior to sampling was similarly short for Streptococcus pneumoniae, beta-streptococci, and Haemophilus influenzae (<= 2 days). In contrast, duration of hospital care and mechanical ventilation were longest for Stenotrophomonas maltophilia (6 and 11 days). For Staphylococcus aureus, the most common Gram-positive isolate, the duration was longer than for S. pneumoniae but shorter than for most Gram-negative bacteria. With the exception of S. maltophilia and Pseudomonas aeruginosa, the median duration of mechanical ventilation was short and similar for most bacteria. In samples taken on the first day of mechanical ventilation, the rate of pathogens expected to be resistant to cefotaxime was 23%. CONCLUSIONS: The occurrence of pathogens with high antibiotic resistance in the lower respiratory tract increases with increased duration of hospital care and mechanical ventilation. An equally important result is that pathogens resistant to third-generation cephalosporins were more common than expected, even after a very short duration of hospital care and mechanical ventilation. PMID- 22324936 TI - Innate immune dysfunction in inflammatory bowel disease. AB - The pathogenetic mechanisms that cause the two types of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are still under investigation. Nevertheless, there is broad agreement that luminal microbes are of particular relevance in the development of these conditions. In recent years, increasing evidence has shown that defects in the innate immunity are at the centre of both types of IBD. The innate intestinal barrier is provided by the epithelium which secretes antimicrobial peptides (so-called defensins) that are retained in the mucus layer. In ileal CD, the alpha-defensins are lacking owing to several Paneth cell defects. In colonic CD, the expression of beta-defensins is inadequate. This may be related to downregulation of the transcription factor peroxisome proliferator-activated receptor-gamma and in some cohorts is associated with a reduced HBD2 gene copy number. In UC, the mucus layer, which protects the host from the enormous amounts of luminal microbes, is defective. This is accompanied by an insufficient differentiation from intestinal stem cells towards goblet cells. All these disturbances in the gut barrier shift the balance from epithelial defence towards bacterial offence. The current treatment for CD and UC is based on suppression of this secondary inflammatory process. In future, patients may benefit from new therapeutic approaches stimulating the protective innate immune system. PMID- 22324937 TI - Enhancement of the electron spin resonance of single-walled carbon nanotubes by oxygen removal. AB - We have observed a nearly 4-fold increase in the electron spin resonance (ESR) signal from an ensemble of single-walled carbon nanotubes (SWCNTs) due to oxygen desorption. By performing temperature-dependent ESR spectroscopy both before and after thermal annealing, we found that the ESR in SWCNTs can be reversibly altered via the molecular oxygen content in the samples. Independent of the presence of adsorbed oxygen, a Curie law (spin susceptibility ? 1/T) is seen from ~4 to 300 K, indicating that the probed spins are finite-level species. For both the pre-annealed and post-annealed sample conditions, the ESR line width decreased as the temperature was increased, a phenomenon we identify as motional narrowing. From the temperature dependence of the line width, we extracted an estimate of the intertube hopping energy; for both sample conditions, we found this hopping energy to be ~1.2 meV. Since the spin hopping energy changes only slightly when oxygen is desorbed, we conclude that only the spin susceptibility, not spin transport, is affected by the presence of physisorbed molecular oxygen in SWCNT ensembles. Surprisingly, no line width change is observed when the amount of oxygen in the SWCNT sample is altered, contrary to other carbonaceous systems and certain 1D conducting polymers. We hypothesize that physisorbed molecular oxygen acts as an acceptor (p-type), compensating the donor-like (n type) defects that are responsible for the ESR signal in bulk SWCNTs. PMID- 22324938 TI - The composition and metabolic activity of child gut microbiota demonstrate differential adaptation to varied nutrient loads in an in vitro model of colonic fermentation. AB - The extent to which the dietary loads of simple sugars, carbohydrates, protein, and fiber impact colonic fermentation in children is unknown. This study assessed the impact of dietary energy on gut microbial communities and metabolism using a three-stage in vitro continuous fermentation model. Two separate models, replicating the proximal, transverse, and distal colon regions, were inoculated with immobilized fecal microbiota from one of two female children. Three different fermentation media were designed to examine the effects of prevalent Western dietary trends on gut microbiota. Media compositions reflected obese (high energy), normal weight (normal energy), and anorectic (low energy) child dietary intakes and were alternately supplied to each microbiota during separate fermentation periods. Gut microbiota demonstrated differential metabolic and compositional adaptation to varied substrate availability. High energy medium was strongly butyrogenic, resulting in significant stimulation of butyrate-producing members of clostridia cluster XIVa, whereas members of cluster IV demonstrated greater adaptive variability. Normal and low energy nutrient loads induced significantly less metabolic activity in both microbiota, with low energy medium inducing a broad reorganization of the commensal community structure. These results suggest a concerted metabolic adaptation in response to nutrient load, exercised by different microbial populations, indicating substantial redundancy in gastrointestinal metabolic pathways. PMID- 22324940 TI - Insights into osteoarthritis from MRI. AB - Magnetic resonance imaging (MRI) has added a new dimension to the study of osteoarthritis, a long-known degenerative joint disease with limited therapeutic options. It has advanced our understanding of joint pathophysiology and identifying that osteoarthritis as a simple 'wear and tear' process of the articular cartilage has indeed become a thing of the past. Recent work has focused on the study and validation of MRI scoring/quantification systems, as well as the identification of MRI predictors of symptoms/disease progression. The latter may serve to identify patients at greater risk for osteoarthritis disease progression to be enrolled in clinical trials. Like all imaging tools, MRI use has its associated problems. Structural changes seen in patients with osteoarthritis are often seen in asymptomatic subjects and this makes an MRI definition of osteoarthritis less straightforward. The ability to pick up multiple structural abnormalities simultaneously and high sensitivity in delineating structural changes can makes interpretation of true pathology more complicated. Although there has been much progress in the field of MRI in osteoarthritis, there remain many clinical/technical issues that need to be addressed. Until more data are obtained from clinical trials, the question of whether MRI is useful in therapeutics intervention in osteoarthritis remains unanswered. PMID- 22324939 TI - Calcium montmorillonite clay reduces urinary biomarkers of fumonisin B1 exposure in rats and humans. AB - Fumonisin B1 (FB1) is often a co-contaminant with aflatoxin (AF) in grains and may enhance AF's carcinogenicity by acting as a cancer promoter. Calcium montmorillonite (i.e. NovaSil, NS) is a possible dietary intervention to help decrease chronic aflatoxin exposure where populations are at risk. Previous studies show that an oral dose of NS clay was able to reduce AF exposure in a Ghanaian population. In vitro analyses from our laboratory indicated that FB1 (like aflatoxin) could also be sorbed onto the surfaces of NS. Hence, our objectives were to evaluate the efficacy of NS clay to reduce urinary FB1 in a rodent model and then in a human population highly exposed to AF. In the rodent model, male Fisher rats were randomly assigned to either FB1 control, FB1 + 2% NS or absolute control group. FB1 alone or with clay was given as a single dose by gavage. For the human trial, participants received NS (1.5 or 3 g day-1) or placebo (1.5 g day-1) for 3 months. Urines from weeks 8 and 10 were collected from the study participants for analysis. In rats, NS significantly reduced urinary FB1 biomarker by 20% in 24 h and 50% after 48 h compared to controls. In the humans, 56% of the urine samples analysed (n = 186) had detectable levels of FB1. Median urinary FB1 levels were significantly (p < 0.05) decreased by >90% in the high dose NS group (3 g day-1) compared to the placebo. This work indicates that our study participants in Ghana were exposed to FB1 (in addition to AFs) from the diet. Moreover, earlier studies have shown conclusively that NS reduces the bioavailability of AF and the findings from this study suggest that NS clay also reduces the bioavailability FB1. This is important since AF is a proven dietary risk factor for hepatocellular carcinoma (HCC) in humans and FB1 is suspected to be a dietary risk factor for HCC and oesophageal cancer in humans. PMID- 22324941 TI - Does HLA-B*2706 protect against ankylosing spondylitis? A meta-analysis. AB - The human leukocyte antigen (HLA)-B*2706 is a relatively rare subtype of HLA-B27. In contrast to most HLA-B27 subtypes, some studies have reported HLA-B*2706 to be protective against ankylosing spondylitis (AS). A systematic review and a meta analysis of available studies was performed to investigate the association of HLA B*2706 with AS. After literature review a random effect meta-analysis was performed. No studies were found comparing the frequency of HLA-B*2706 in AS patients and controls. Meta-analysis of seven studies using HLA-B27-positive AS patients and controls showed a protective effect of HLA-B*2706 on development of AS in HLA-B27 individuals (odds ratio = 0.128, 95% CI = 0.043-0.378, P < 0.001). The results of the meta-analysis of HLA-B*2706 in HLA-B27-positive patients and controls is preliminary evidence of a protective effect of HLA-B*2706 against AS in the population. There is a clear need for additional studies on HLA-B*2706 in AS. Due to the fact that HLA-B*2706 is more or less restricted to Southeast Asia, researchers in this part of the world may have an essential role in performing these studies. PMID- 22324942 TI - Urine sVCAM-1 and sICAM-1 levels are elevated in lupus nephritis. AB - AIM: We sought to evaluate the relationship of urine levels of soluble cellular adhesion molecules sVCAM-1 (vascular) and sICAM-1 (intercellular) in systemic lupus erythematosus (SLE) patients with or without lupus nephritis, and to explore their correlation with renal disease activity. METHODS: Paired serum and urine samples of 121 Asian SLE patients, and urine samples of 19 normal healthy controls were collected. Demographic data, disease activity and damage scores, and selected laboratory parameters, including levels of anti-double stranded DNA antibody, complements C3, C4, and creatinine were captured. Renal disease activity was scored with renal SLE Activity Measure revised (rSLAM-R). Serum and urine sVCAM-1 and sICAM-1 levels were assayed by enzyme-linked immunosorbent assay. RESULTS: Urinary sVCAM-1 and sICAM-1 were elevated in SLE patients compared to controls. Significantly higher levels of urine sVCAM-1 found in patients with active lupus nephritis correlated with rSLAM-R. In addtion, significantly more patients with active lupus nephritis had detectable levels of urine sICAM-1, but no correlation with renal activity was observed. CONCLUSION: Urinary sVCAM-1 may serve as a potential biomarker for early diagnosis of lupus nephritis as levels correlated with even mild abnormalities of urine sediment. In addition, both urine sVCAM-1 and sICAM-1 levels may be useful in identifying patients at risk of lupus nephritis. PMID- 22324943 TI - Vitamin D levels: its relationship to bone mineral density response and disease activity in premenopausal Malaysian systemic lupus erythematosus patients on corticosteroids. AB - AIM: To determine if baseline vitamin D levels would influence the gain in bone mineral density (BMD) in female systemic lupus erythematosus (SLE) patients on corticosteroids (CS) taking bone-active medication. METHOD: Premenopausal SLE patients participating in a trial assessing the efficacy of calcium alone, calcitriol and calcium, and alendronate and calcium, on BMD in patients on CS, were studied. Patients were randomly allocated to the treatment groups at the start of the study and followed up for 2 years. Serum 25-hydroxy vitamin D [25(OH)D] was measured at baseline. RESULTS: Thirty-eight patients were studied. One (2%) patient had osteoporosis, nine (24%) had osteopenia and all others had normal BMD. The mean baseline 25(OH)D levels were 21.6 +/- 4.6 ng/mL (+/- 1 SD). Twelve (32%) patients had vitamin D deficiency [25(OH)D < 20 ng/mL]. There was a significant negative correlation between SLEDAI scores and 25(OH)D levels, that is, patients with high SLEDAI scores had significantly lower 25(OH)D levels (P = 0.033). Left femoral neck BMD was significantly lower in the deficient compared to insufficient group (P = 0.042). There was a trend toward better BMD gain at 2 years in the vitamin D insufficient compared to the deficient group, which did not reach statistical significance. CONCLUSION: This study showed that in female SLE patients, low vitamin D levels are associated with higher disease activity and suggests that patients who have higher vitamin D levels have a better BMD response during treatment with bone-active agents. PMID- 22324944 TI - Identification of activated cytokine pathways in the blood of systemic lupus erythematosus, myositis, rheumatoid arthritis, and scleroderma patients. AB - AIM: To develop genomic signatures of seven cytokines involved in the pathogenesis of rheumatic diseases such as systemic lupus erythematosus (SLE), dermatomyositis (DM), polymyositis (PM), rheumatoid arthritis (RA), or systemic scleroderma (SSc) that could potentially help identify patients likely to respond to therapies that target these individual cytokines. METHODS: Over-expressed transcripts in the whole blood (WB) were identified from 262 SLE, 44 DM, 33 PM, 38 SSc and 89 RA subjects and compared to 24 healthy subjects using Affymetrix arrays. Cytokine-inducible gene signatures such as type I interferon (IFN), tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-10, IL-13, IL-17, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were assessed in the WB of these subjects to identify subpopulations showing activation of specific cytokine pathways. RESULTS: Significant activation of the type I IFN pathway in a population of five diseases studied was universally observed. The TNF-alpha and IL-1beta pathways were activated in subgroups of PM and RA subjects, respectively, with another subgroup of RA subjects showing activation of the IL-13 pathway. The GM-CSF pathway was activated in a subgroup of SSc subjects and the IL-17 pathway was activated in subgroups of all diseases except SLE. CONCLUSIONS: A novel gene expression measurement of activated cytokines in five different rheumatic diseases is presented. Characterizing the cytokine pathways most activated in specific patient subpopulations has the potential to help target the appropriate patient populations for corresponding anti-cytokine therapies. PMID- 22324945 TI - Interleukin-6 upregulates expression of ADAMTS-4 in fibroblast-like synoviocytes from patients with rheumatoid arthritis. AB - AIM: A disintegrin-like and metalloproteinase with thrombospondin type 1 motif (ADAMTS)-4 and ADAMTS-5 play crucial roles in the cleavage of aggrecan. Several recent studies have demonstrated the effect of cytokines such as interleukin (IL) 1beta, tumor necrosis factor-alpha and transforming growth factor-beta on the expression of ADAMTS-4 and ADAMTS-5 in fibroblast-like synoviocytes (FLS). However, the effect of IL-6 remains unclear. The aim of this study is to investigate the expression of ADAMTS-4 and ADAMTS-5 in FLS of rheumatoid arthritis (RA) patients after IL-6 stimulation. METHOD: Immunohistochemical staining was performed to examine the expression and localization of ADAMTS-4 and ADAMTS-5 in RA synovium. FLS isolated from RA patients were stimulated by IL-6 and soluble IL-6 receptor (sIL-6R) in the presence or absence of anti-IL-6R antibody, and the expression levels of ADAMTS-4 and ADAMTS-5 messenger RNA (mRNA) were assessed using real-time polymerase chain reaction. Furthermore, the IL-6 signaling pathway for regulation of ADAMTS-4 and ADAMTS-5 was also examined. RESULTS: Staining for ADAMTS-4 and ADAMTS-5 was mainly observed in the sublining layer of synovial membrane and pannus. The expression of ADAMTS-4 mRNA was increased by IL-6/sIL-6R, whereas that of ADAMTS-5 was decreased. Anti-IL-6R antibody suppressed the effect of IL-6/sIL-6R. Mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) kinase (MEK)1/2 inhibitor U0126 inhibited the effect of IL-6/sIL-6R on ADAMTS-4 mRNA expression in FLS. Signal transducer and activator of transcription 3 (STAT3) inhibitor parthenolide inhibited the effect of IL-6/sIL-6R on ADAMTS-4, and downregulated ADAMTS-5 expression. CONCLUSION: These results suggest IL-6 may participate in cartilage destruction in RA as an inducer of ADAMTS-4 expression from FLS. PMID- 22324946 TI - Advanced glycation end-products inhibition improves endothelial dysfunction in rheumatoid arthritis. AB - AIM: Chronic inflammation in rheumatoid arthritis is associated with vascular endothelial dysfunction. The objective was to study the efficacy and safety of advanced glycation end products (AGEs) inhibitor (benfotiamine 50 mg + pyridoxamine 50 mg + methylcobalamin 500 MUg, Vonder((r)) (ACME Lifescience, Baddi, Himachal Pradesh, India)) on endothelial function in rheumatoid arthritis (RA). METHODS: Twenty-four patients with established active RA with high disease activity (Disease Activity Score of 28 joints [DAS28 score] > 5.1) despite treatment with stable doses of conventional disease-modifying antirheumatic drugs were investigated. Inflammatory disease activity (DAS28 and Health Assessment Questionnaire-Disability Index [HAQ-DI] scores, erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]), markers of endothelial dysfunction, serum nitrite concentration and endothelium-dependent and -independent vasodilation of the brachial artery were measured before and after 12 weeks therapy with twice a day oral AGEs inhibitor. RESULTS: After treatment, flow-mediated vasodilation improved from 9.64 +/- 0.65% to 15.82 +/- 1.02% (P < 0.01), whereas there was no significant change in endothelium-independent vasodilation with nitroglycerin and baseline diameter; serum nitrite concentration significantly reduced from 5.6 +/- 0.13 to 5.1 +/- 0.14 MUmol/L (P = 0.004), ESR from 63.00 +/- 3.5 to 28.08 +/- 1.5 mm in the first h (P < 0.01) and CRP levels from 16.7 +/- 4.1 to 10.74 +/- 2.9 mg/dL (P < 0.01). DAS28 and HAQ-DI scores were significantly reduced, from 5.9 +/ 0.17 to 3.9 +/- 0.17 (P < 0.01) and 4.6 +/- 0.17 to 1.7 +/- 0.22 (P < 0.01), respectively. CONCLUSIONS: Advanced glycation end products inhibitor improves endothelial dysfunction and inflammatory disease activity in RA. In RA, endothelial dysfunction is part of the disease process and is mediated by AGEs induced inflammation. PMID- 22324947 TI - Frequency of anemia of inflammation in patients with ankylosing spondylitis requiring anti-TNFalpha drugs and therapy-induced changes. AB - OBJECTIVE: Primary: to evaluate the frequency of anemia of inflammation (AOI) in a clinical series of patients with ankylosing spondylitis (AS) requiring anti-TNF (tumor necrosis factor) agents. Secondary: to examine anti-TNF therapy-induced changes in AOI. METHOD: Prospective, follow-up, 6-month study of all consecutive, new patients with AS requiring anti-TNFalpha drugs observed between January 2004 and December 2008. AOI was defined according to WHO criteria. PRIMARY OUTCOME MEASURE: the proportion of patients showing AOI at baseline. SECONDARY OUTCOME MEASURES: the proportion of patients achieving resolution of AOI at the 6-month visit; the proportion of patients achieving any improvement in haemoglobin (Hb); the proportion of patients with any improvement in blood results. RESULTS: One hundred and six patients (42 women and 64 men; mean age: 46 years) with AS were evaluated. Sixteen of these (15%) presented with AOI at baseline. After 6 months therapy 13 patients (81%) resolved AOI while two presented an Hb level reduction. After 6 months therapy we did not find a significant statistical improvement in red blood cell numbers (P = 0.85) and transferrin (P = 0.08) levels. Hb, mean corpuscular volume (MCV), iron, ferritin, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) improved reaching statistical significance (P = 0.0002, 0.0001, 0.001, 0.014; 0.007, 0.004, respectively). CONCLUSION: We found 15% frequency of AOI among a selected series of patients with AS. After 6 months of anti-TNFalpha therapy AOI resolved in the majority of patients with significant improvement of Hb, MCV, CRP and ESR levels. PMID- 22324948 TI - Efficacy and safety of methotrexate in articular and cutaneous manifestations of systemic lupus erythematosus. AB - AIM: A prospective open-label study comparing the efficacy and safety of methotrexate (MTX) and chloroquine (CQ) in articular and cutaneous manifestations of systemic lupus erythematosus (SLE). METHODS: Consecutive SLE patients were randomly assigned to either 10 mg MTX weekly or 150 mg CQ daily during 24 weeks. Outcome measures were: numbers of swollen and tender joints, duration of morning stiffness, visual analog scale (VAS) for articular pain, physician global assessment index, patient global assessment index, SLE Disease Activity Index (SLEDAI), disappearance of skin rash and erythrocyte sedimentation rate (ESR). RESULTS: Forty-one patients consented to participate, 15 were allocated in the MTX group and 26 in the CQ group. Two patients on MTX dropped out due to side effects and two in the CQ group, one due to side-effects and one due to inefficacy. Baseline demographic, clinical and laboratory parameters of the two groups were nearly identical. In both groups the clinical and laboratory parameters improved significantly over 24 weeks, except the ESR in the MTX group. The results of the outcome measures at the end of the trial did not differ significantly between the two groups, except morning stiffness (P < 0.05 in favor of the MTX group) and ESR (P < 0.01 in favor of the CQ group). Rise of serum alanine aminotransferase was observed in two cases in the MTX group and in none in the CQ group. CONCLUSION: Low-dose MTX appears to be as effective as CQ in patients with articular and cutaneous manifestations of SLE, having an acceptable toxicity profile. Results of this prospective study need to be confirmed in a larger study. PMID- 22324949 TI - Diacerein as adjuvant to diclofenac sodium in osteoarthritis knee. AB - AIM: To evaluate clinical effectiveness of diacerein as an adjuvant to diclofenac sodium in treatment of Indian patients with symptomatic osteoarthritis (OA) knee. METHODS: This is a prospective, double-blind, placebo-controlled and intention-to treat study. An initial washout period of 1 week, was followed by 3 months treatment period during which patients were randomly divided to receive either capsule diacerein 50 mg or matched placebo once daily for the first month and twice daily for the next 2 months with diclofenac sodium 75 mg sustained release tablet once daily given to both groups. Patients were observed for one more month, using paracetamol as rescue therapy. Treatment efficacy was assessed by a visual analogue scale (VAS) and the Western Ontario and McMaster University (WOMAC) Osteoarthritis Index, patient and physician global assessment of OA, daily paracetamol intake. RESULTS: Of 84 patients screened, 74 patients formed the intent-to-treat population (37 patients in each group). At baseline, both groups were comparable and at the third month functional index and pain intensity were better in the diacerein group (VAS 15.33 +/- 5.07; WOMAC 15.9 +/- 2.40) as compared to the placebo group (VAS 22.83 +/- 6.90;WOMAC 36.8 +/- 2.92; P < 0.05). When analyzed at the fourth month, improvement persisted in the iacerein group (VAS 14.83 +/- 5.16; WOMAC 16 +/- 2.5) as compared to placebo group (VAS 33 +/- 7.72; WOMAC 48.26 +/- 3.5; P < 0.05), demonstrating the carry-over effect of diacerein, which was confirmed by lesser paracetamol consumption in the diacerein group (5.967 +/- 0.8087) as compared to the placebo group (12.433 +/- 2.128; P < 0.05). CONCLUSION: Use of diacerein and diclofenac sodium together decreases pain and improves joint function significantly more than diclofenac alone in OA knee. PMID- 22324950 TI - Serum levels of anti-streptolysin O antibodies: their role in evaluating rheumatic diseases. AB - BACKGROUND: Family physicians measure serum levels of anti-streptolysin O antibodies (ASO) in the routine evaluation of patients with rheumatic conditions. AIM: To evaluate the significance of elevated serum ASO titer in hospitalized patients with various clinical conditions. PATIENTS AND METHODS: We retrieved the names of all patients in whom ASO serum titer was tested in our hospital during two successive years. We chose only those with titers of 1 : 160 or greater (cut off level < 1 : 80) or with no titer. Their charts were reviewed and the causes for their hospitalization and the reasons for requesting the tests were identified. We also measured the ASO serum titer in 60 healthy individuals. RESULTS: Six hundred and twenty-five patients were tested for ASO serum levels; 129 patients were negative. In 291 (44%) patients tests were positive at low titers (< 1 : 160). In 205 (33%) the serum titers of ASO were >= 1 : 160. We analyzed two groups: those with high ASO titers (>= 1 : 160) (group 1) and those who were negative for this test (group 2). In group 1, streptococcal cultures were positive only in 14% of the patients with elevated ASO. There was no correlation between ASO serum levels and erythrocyte sedimentation rate, C reactive protein or rheumatoid factor. In only five individuals (8%) of the healthy cohort, was ASO significantly elevated. CONCLUSIONS: Elevated ASO titers can be found in various clinical conditions other than the typical post streptococcal associated diseases. In these cases it is not necessarily accompanied by positive culture and does not correlate with inflammatory parameters. PMID- 22324951 TI - Low C3 levels is associated with neutropenia in a proportion of patients with myelodysplastic syndrome: retrospective analysis. AB - BACKGROUND: Myelodysplastic syndrome (MDS) is a clonal disorder characterized by ineffective hematopoiesis. MDS patients are known to manifest overt rheumatic manifestations and have distinct immunological abnormalities but their clinical significance has yet to be elucidated. AIM: To investigate the prevalence of autoimmune or rheumatic manifestations in the course of MDS and serological immunological abnormalities which have been detected at presentation and to determine their clinical significance. METHODS: One hundred and eleven patients diagnosed as having MSD between 2001 and 2004 were identified. Their clinical and serologic features on medical records were retrospectively reviewed. RESULTS: Of 111 patients with MDS, 25 showed 27 autoimmune or rheumatic manifestations. On dividing the cohort into two groups, with and without autoimmune or rheumatic manifestations, the two groups were not statistically different in survival. Serological immunological abnormalities were observed by variable rate, but had no association with compatible clinical manifestations. C3 hypocomplementemia was observed as high as 45.9% and the C3 hypocomplementemic subgroup had more severe cytopenia of red cell and white cell lineages and was dominant in the low-risk International Prognostic Scoring System category. CONCLUSIONS: Our data indicates that a distinct subset of MDS, demonstrating complement activation, has more severe cytopenias, which suggest complement activation contributes to the pathogenesis of autoimmune cytopenia in MDS. PMID- 22324952 TI - Nailfold capillaroscopy by digital microscope in an Indian population with systemic sclerosis. AB - AIM: Nailfold capillaroscopy (NFC) is a simple, non-invasive method with exceptional predictive value for the analysis of microvascular abnormalities, especially in systemic sclerosis (SSc) but remains underutilized due to cost factors of the nailfold videocapillaroscope, lack of expertise and availability issues. The aim of this study was to establish the utility of an inexpensive digital microscope to study NFC changes in SSc in correlation with disease subsets and extent of skin involvement. METHODS: Twenty-two diffuse cutaneous SSc (DSS), 20 limited cutaneous SSc (LSS) patients and 42 controls were evaluated with NFC using a digital microscope at 30* and 100* magnification. Digital micrographs were used to study qualitative and quantitative changes in microvasculature. RESULTS: The capillary density was significantly less in all cases of SSc as compared to controls (5.3 +/- 1.4 vs. 8.7 +/- 1.2; P < 0.00001). Disorganized architecture was much more prevalent in DSS versus LSS (86.4%vs. 25%). The vascular deletion score (VDS) was significantly higher in DSS as compared to LSS (P < 0.0001). Scleroderma pattern (SP) was seen in 18 (81.9%) and 15 (75%) of patients with DSS and LSS, respectively. Only 4% of normal subjects showed non-specific pattern and none showed SP. The mean modified Rodnan skin score (MRSS) was positively correlated with vascular deletion score (r = 0.572; P < 0.001) and negatively with capillary density (r = -0.8; P < 0.001). CONCLUSION: Nailfold capillaroscopy changes in SSc are related to disease subset and MRSS. NFC with digital microscope is a simplified, inexpensive, outpatient procedure with results comparable to previous studies. PMID- 22324953 TI - South Australian Scleroderma Register: autoantibodies as predictive biomarkers of phenotype and outcome. AB - AIM: To investigate the relationship between scleroderma-specific autoantibodies and clinical phenotype and survival in South Australian patients with scleroderma. METHOD: Two cohorts of patients were studied from the South Australian Scleroderma Register (SASR). In the first, the sera of 129 consecutive patients were analyzed for anticentromere (ACA), anti-Scl70, anti-RNA polymerase III, anti-U1RNP, anti-Th/To, anti-Pm/Scl, anti-Ku and anti-fibrillarin antibodies using the Euroline immunoblot assay. Statistical analysis was performed to look for a significant association between specific antibodies and various clinical features. In the second cohort survival from first symptom onset was analyzed in 285 patients in whom the autoantibody profile was available, including ACA, Anti Scl70, anti-U1RNP and anti-RNA polymerase III measured using multiple methods. Survival analysis compared mortality between different groups of patients with specific antibodies. RESULTS: ACA, Th/To and Ku antibodies were associated with limited scleroderma, Scl70 and RNA Pol III antibodies were associated with diffuse scleroderma and antibodies to U1RNP were associated with overlap syndrome. Significant associations between Scl70 and interstitial lung disease (P = 0.004), RNA Pol III and renal crisis (P = 0.002), U1RNP and pulmonary hypertension (P = 0.006) and Th/To and pulmonary hypertension (P = 0.034) were seen. Trends were observed with an increased frequency of lung disease with Pm/Scl and Th/To and an increased frequency of myositis with Ku. The presence of Scl70, RNA Pol III and U1RNP was associated with significantly reduced survival as compared with patients with ACA. CONCLUSIONS: Scleroderma-specific autoantibodies are associated with clinical phenotype and survival. PMID- 22324954 TI - Familial rheumatoid arthritis in patients referred to rheumatology clinics of Tabriz, Iran. AB - BACKGROUND: The familial clustering of rheumatoid arthritis (RA) in first and second degree relatives of patients supports the role of genetic factors. The proportion of heredity in its development is roughly 60%; however, most individuals closely related to someone with RA do not get the disease. Considering the lack of sufficient data on the familial aggregation of RA in Iran, we designed this study for clarifying the familial prevalence of RA. OBJECTIVE: To determine the prevalence of RA among relatives of patients with RA and to evaluate the mean disease onset age in relatives. METHODS: In a longitudinal study from July 2008 to July 2010, we followed 210 unrelated patients with RA and their first and second degree relatives (FDR+ and SDR+), by interviewing and physical examination of those with symptoms, to ascertain prevalence. Familial RA was defined by presence of at least two siblings fulfilling the 1987 ACR criteria for RA. RESULTS: We demonstrated that 17.6% of patients have at least one affected relative. The prevalence of RA in the family of studied patients was 0.83% (42 people). Thirty-two in FDR+ and 10 people in SDR+ (2.53% and 0.26% of all family), also 1.12% in female relatives and 0.39% in male relatives had RA. The odds ratio for FDR/SDR was 2.52. The mean age at disease onset in relatives was 42.30 +/- 1.51 years in FDR+ and 34.40 +/- 2.10 years in the SDR+ group (0.03). CONCLUSION: The risk of RA is greatest in FDR+ and is likely to be due to a combination of inherited and environmental factors. PMID- 22324955 TI - Prevalence and clinical pattern of juvenile idiopathic arthritis in a semi-urban area of Bangladesh. AB - OBJECTIVE: To determine the prevalence and clinical pattern of juvenile idiopathic arthritis (JIA) in a semi-urban area of Bangladesh. METHODOLOGY: A cross-sectional study was carried out among 16 270 children who were selected by using multistage sampling technique from a community of approximately 105 986 children in the Narayanganj district, Bangladesh. Duration of the study was from November 2008 to December 2009. Examinations of the suspected JIA patients were done by the authors in the community as well as in the pediatric rheumatology follow-up clinic at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. RESULTS: The estimated point prevalence of JIA was 60.5 per 100 000 children. In total 10 patients were identified among 16 270 children. Girl : boy ratio was 2.3 : 1.0. The subgroup distribution showed oligoarticular JIA in the majority of patients (60%). CONCLUSIONS: Prevalence of JIA in this study in a semi-urban area of Bangladesh was consistent with established population-based studies in developed countries. Clinical pattern of JIA patients also had similarities with reports from Western countries. PMID- 22324956 TI - Detection of anti-nuclear antibody by immunofluorescence assay and enzyme immunoassay in childhood systemic lupus erythematosus: experience from Bangladesh. AB - BACKGROUND: Systemic lupus erythematosus (SLE) is a multisystem, chronic but often episodic, autoimmune disease that is characterized by the presence of antinuclear antibodies (ANA). The criteria set by American College of Rheumatology are widely used for diagnosis of SLE. Elevation of ANA titer is the most sensitive of the ACR criteria. There are different methods for detection of ANA. Indirect immunofluorescence (ANA-IFA) and enzyme immunoassay (ANA-EIA) are commonly used methods. The sensitivity of ANA-IFA using HEp-2 cell substrate is 90-100% in systemic rheumatic diseases. In Bangladesh most of the laboratories use ANA-EIA for detection of ANA. As the sensitivity of ANA-EIA is lower than ANA IFA it might be that we are missing many cases of ANA positivity in childhood SLE cases. OBJECTIVES: To detect ANA by immunofluorescence assay using HEp-2 cell substrate and enzyme immunoassay in childhood SLE and to compare the diagnostic performance of these methods. MATERIAL AND METHODS: This is a cross-sectional analytical study. A total of 40 patients were enrolled. Among them 20 were childhood SLE cases. Another 20 patients of childhood rheumatic diseases other than SLE were taken as the disease control group. RESULT: In childhood SLE cases, 100% were ANA-positive by IFA and 55% were ANA positive by EIA. The sensitivity of ANA-IFA was 100%. In contrast, sensitivity of ANA-EIA was 55%. CONCLUSION: ANA-IFA is superior to ANA-EIA for detection of ANA in childhood SLE patients. ANA-IFA should be the primary screening test for children with clinical features suggestive of SLE. PMID- 22324958 TI - The role of anti-cyclic citrullinated peptide and rheumatoid factor in diagnosis of rheumatoid arthritis. PMID- 22324959 TI - Non-malignant lytic lesions of bone. PMID- 22324960 TI - An unusual case of polyarthritis, skin nodules and patchy skin thickening: fibroblastic rheumatism. PMID- 22324961 TI - Massive ascites as a presenting feature of lupus. PMID- 22324962 TI - Excellence in Rheumatology 2012 25-28 January Madrid. PMID- 22324963 TI - Comment on: Churg-Strauss syndrome: a retrospective study of 11 cases from a single center in Japan. PMID- 22324964 TI - Superior mesenteric artery syndrome in an adult rheumatoid arthritis patient. PMID- 22324965 TI - Serum sickness and severe angioedema following rituximab therapy in RA. PMID- 22324966 TI - Palmar fasciitis: a para-neoplastic phenomenon indicating recurrence of non small cell lung cancer - case report and review of the literature. PMID- 22324967 TI - Predictors of mental health in adults with congenital craniofacial conditions attending the Australian craniofacial unit. AB - Objective : Adults with craniofacial conditions experience more psychosocial problems than adults in the general population, but little is known about the factors that render a person more or less susceptible to these problems. Guided by research on adults with other conditions that affect appearance, this study examined predictors of psychosocial outcome in adults with craniofacial conditions. Design : Single-sample cross-sectional design. Setting : The Australian Craniofacial Unit, Women's and Children's Hospital, Adelaide, one of the main craniofacial treatment centers in Australia. Participants : Adults (N = 93; 36.9% of the potential sample) with congenital craniofacial conditions (excluding cleft lip and/or cleft palate) who were treated in the Australian Craniofacial Unit. Main Outcome Measures : All participants completed measures assessing anxiety, depression, and quality of life (Hospital Anxiety and Depression Scale, Short-Form Health Survey) and variables predicted to affect these outcomes (SF-36 Health Survey - Multidimensional Scale of Perceived Social Support, Rosenberg Self-Esteem Scale, Cleft Satisfaction Profile, Brief Fear of Negative Evaluation Scale, Derriford Appearance Scale). Results : Multiple regression analyses revealed that anxiety was predicted by social support, self esteem, and fear of negative evaluation, while depression was predicted by self esteem and social support. Physical quality of life was not predicted by any of the measures. Satisfaction with appearance, gender, age, and education were not related to outcome. Conclusions : Interventions designed to increase perceived social support and self-esteem and reduce fear of negative evaluation appear to be indicated and may assist in establishing a causal relationship between these variables. PMID- 22324968 TI - Directly measured mucosal pressures produced by the i-gelTM and Laryngeal Mask Airway SupremeTM in paralysed anaesthetised patients. AB - The i-gelTM and LMA SupremeTM are extraglottic airway devices with non-inflatable and inflatable cuffs, respectively. We hypothesised that directly measured mucosal pressures would differ between these devices in anesthetised paralysed patients. Thirty patients were randomly allocated to receive one of these two devices. Four pressure sensors were attached to all airway devices used to measure mucosal pressure at the base of the tongue, the distal oropharynx, the hypopharynx and the pyriform fossa. At these four places, median (IQR [range]) i gel mucosal pressures were 8.0 (2.7-10.7 [0-26.7]), 5.0 (2.7-7 [1.0-37.3]), 9.3 (2.7-13.3 [0-22.7] and 8.0 (2.7-10.7 [0-25.3]) cmH(2)O, respectively, and for the LMA Supreme, these were 5.0 (0.5-8.0 [0-33]), 4.0 (1.3-9.3 [0-24]), 10.7 (4-17.3 [0-26.7]) and 8.0 (0-10.7 [0-36]) cmH(2)O, respectively. Mucosal pressures were low and similar for both devices. The LMA Supreme mucosal pressures were higher in the hypopharynx than in the distal oropharynx (p = 0.04) and base of the tongue (p = 0.011). There were no pressure differences between the locations for the i-gel. PMID- 22324969 TI - Lifetime history of indoor tanning in young people: a retrospective assessment of initiation, persistence, and correlates. AB - BACKGROUND: Despite educational and public health campaigns to convey the risks of indoor tanning, many individuals around the world continue to engage in this behavior. Few descriptive studies of indoor tanning have collected information pertaining to the lifetime history of indoor tanning, thereby limiting our ability to understand indoor tanning patterns and potentially target interventions for individuals who not only initiate, but continue to persistently engage in indoor tanning. METHODS: In-person interviews elicited detailed retrospective information on lifetime history of indoor tanning among white individuals (n = 401) under age 40 seen by a dermatologist for a minor benign skin condition. These individuals were controls in a case-control study of early onset basal cell carcinoma. Outcomes of interest included ever indoor tanning in both males and females, as well as persistent indoor tanning in females - defined as females over age 31 who tanned indoors at least once in the last three or all four of four specified age periods (ages 11-15, 16-20, 21-30 and 31 or older). Multivariate logistic regression was used to identify sociodemographic and lifestyle correlates of ever and persistent indoor tanning in females. RESULTS: Approximately three-quarters (73.3%) of females and 38.3% of males ever tanned indoors, with a median age of initiation of 17.0 and 21.5, respectively. Among indoor tanners, 39.3% of females and 21.7% of males reported being burned while indoor tanning. Female ever indoor tanners were younger, had darker color eyes, and sunbathed more frequently than females who never tanned indoors. Using unique lifetime exposure data, 24.7% of female indoor tanners 31 and older persistently tanned indoors starting as teenagers. Female persistent indoor tanners drank significantly more alcohol, were less educated, had skin that tanned with prolonged sun exposure, and sunbathed outdoors more frequently than non persistent tanners. CONCLUSIONS: Indoor tanning was strikingly common in this population, especially among females. Persistent indoor tanners had other high risk behaviors (alcohol, sunbathing), suggesting that multi-faceted behavioral interventions aimed at health promotion/disease prevention may be needed in this population. PMID- 22324970 TI - The role of phylogeny in desert rodent community assembly. AB - Recent advances in molecular genetics and phylogenetic reconstruction have the potential to transform ecology by providing new insights into the historical evolution of ecological communities. This study by Stevens and collaborators complements decades of previous research on desert rodents, by combining data from a field study and a phylogenetic tree for Mojave Desert rodents to address patterns and processes of community assembly. The number of coexisting rodent species is positively correlated, and the average phylogenetic distance among these species is negatively correlated with perennial plant species richness. As rodent species diversity increases along a gradient of increasing environmental heterogeneity, communities are composed of increasingly related species: there is a consistent pattern of phylogenetic structure from over-dispersed through random to clumped. I discuss this pattern in the light of complementary results of previous studies. This paper is noteworthy for calling attention to still unanswered questions about how the historical events of speciation, colonization, extinction, and trait evolution and their relationship to past climates and vegetation have given rise to current patterns of community organization. PMID- 22324971 TI - The relationship between coronary risk factors and elevated 1-h postload plasma glucose levels in patients with established coronary heart disease. AB - OBJECTIVE: Recent studies have shown that an elevated 1-h postload plasma glucose (1hPG) is able to identify subjects with normal glucose tolerance (NGT) at high risk for future type 2 diabetes and atherosclerotic cardiovascular disease. However, clinical studies about the characteristics of coronary heart disease (CHD) patients with elevated 1hPG are lacking. The aim of this study was to analyse the 1hPG level in CHD patients with NGT. METHODS: A total of 204 CHD patients with NGT were recruited. Subjects underwent an oral glucose tolerance test, echocardiography and coronary angiography. Demographic data were recorded and blood samples obtained. According to the 1hPG cut-off point of 8.6 mm, patients were divided into two groups: 1hPG >= 8.6 mm (n = 65) and 1hPG < 8.6 mm (n = 139). RESULTS: Compared with the 1hPG < 8.6 mm group, subjects with 1hPG >= 8.6 mm had a worse metabolic profile, exhibiting significantly higher body mass index, systolic blood pressure, triglyceride level and lower HDL-cholesterol level. Plasma high-sensitivity CRP (hsCRP) levels were higher in the 1hPG >= 8.6 mm group than in the 1hPG < 8.6 mm group. Coronary angiography revealed that single-vessel changes were more frequent in the 1hPG < 8.6 mm group, but there were no significant differences in the Gensini score. CONCLUSIONS: Patients with CHD with 1hPG >= 8.6 mm have a worse metabolic profile, higher levels of hsCRP and multi-vessel coronary atherosclerosis. These findings suggest that, in patients with CHD, elevated 1hPG increases coronary risk factors and may be a marker for early-stage glucose intolerance. PMID- 22324972 TI - Oxidative stress protection and stomatal patterning as components of salinity tolerance mechanism in quinoa (Chenopodium quinoa). AB - Two components of salinity stress are a reduction in water availability to plants and the formation of reactive oxygen species. In this work, we have used quinoa (Chenopodium quinoa), a dicotyledonous C3 halophyte species displaying optimal growth at approximately 150 mM NaCl, to study mechanisms by which halophytes cope with the afore-mentioned components of salt stress. The relative contribution of organic and inorganic osmolytes in leaves of different physiological ages (e.g. positions on the stem) was quantified and linked with the osmoprotective function of organic osmolytes. We show that the extent of the oxidative stress (UV-B irradiation) damage to photosynthetic machinery in young leaves is much less when compared with old leaves, and attribute this difference to the difference in the size of the organic osmolyte pool (1.5-fold difference under control conditions; sixfold difference in plants grown at 400 mM NaCl). Consistent with this, salt grown plants showed higher Fv/Fm values compared with control plants after UV-B exposure. Exogenous application of physiologically relevant concentrations of glycine betaine substantially mitigated oxidative stress damage to PSII, in a dose-dependent manner. We also show that salt-grown plants showed a significant (approximately 30%) reduction in stomatal density observed in all leaves. It is concluded that accumulation of organic osmolytes plays a dual role providing, in addition to osmotic adjustment, protection of photosynthetic machinery against oxidative stress in developing leaves. It is also suggested that salinity-induced reduction in stomatal density represents a fundamental mechanism by which plants optimize water use efficiency under saline conditions. PMID- 22324973 TI - Tedizolid (TR-701): a new oxazolidinone with enhanced potency. AB - INTRODUCTION: Tedizolid phosphate (TR-701) is a new oxazolidinone prodrug that is transformed in the serum into the active drug tedizolid (TR-700). Tedizolid acts by inhibiting protein synthesis and has broad activity against Gram-positive pathogens, including strains that are resistant to linezolid. AREAS COVERED: This review summarizes the currently available data on this new antimicrobial agent. In vitro activity, pharmacokinetics/pharmacodynamics, clinical efficacy and safety are all addressed. EXPERT OPINION: Tedizolid will provide a useful addition to the antimicrobial armamentarium, particularly in complicated skin and skin structure infections, due to its high oral bioavailability and once-daily dosing. The results of future studies will serve to better position tedizolid among the newly approved agents for infections caused by Gram-positive organisms. PMID- 22324974 TI - trans-[Ru(II)(dpp)Cl2]: a convenient reagent for the preparation of heteroleptic Ru(dpp) complexes, where dpp is 2,9-di(pyrid-2'-yl)-1,10-phenanthroline. AB - The reaction of 2,9-di(pyrid-2'-yl)-1,10-phenanthroline (dpp) with [RuCl(3).3H(2)O] or [Ru(DMSO)(4)Cl(2)] provides the reagent trans [Ru(II)(dpp)Cl(2)] in yields of 98 and 89%, respectively. This reagent reacts with monodentate ligands L to replace the two axial chlorides, affording reasonable yields of a ruthenium(II) complex with dpp bound tetradentate in the equatorial plane. The photophysical and electrochemical properties of the tetradentate complexes are strongly influenced by the axial ligands with electron donating character to stabilize the ruthenium(III) state, shifting the metal-to ligand charge-transfer absorption to lower energy and decreasing the oxidation potential. When the precursor trans-[Ru(II)(dpp)Cl(2)] reacts with a bidentate (2,2'-bipyridine), tridentate (2,2';6,2''-terpyridine), or tetradentate (itself) ligand, a peripheral pyridine on dpp is displaced such that dpp binds as a tridentate. This situation is illustrated by an X-ray analysis of [Ru(dpp)(bpy)Cl](PF(6)). PMID- 22324975 TI - Purification and characterization of novel organic-solvent-tolerant beta-amylase and serine protease from a newly isolated Salimicrobium halophilum strain LY20. AB - A halophilic isolate Salimicrobium halophilum strain LY20 producing extracellular amylase and protease was isolated from Yuncheng, China. Production of both enzymes was synchronized with bacterial growth and reached a maximum level during the early-stationary phase. The amylase and protease were purified to homogeneity with molecular weights of 81 and 30 kDa, respectively. Optimal amylase activity was observed at 70 degrees C, pH 10.0% and 10% NaCl. Complete inhibition by EDTA, diethyl pyrocarbonate (DEPC), and phenylarsine oxide (PAO) indicated that the amylase was a metalloenzyme with histidine and cysteine residues essential for its catalysis. Maltose was the main product of starch hydrolysis, indicating an beta-amylase activity. The purified protease from LY20 showed highest activity at 80 degrees C, pH 10.0% and 12.5% NaCl. Complete inhibition was shown by phenylmethylsulfonyl fluoride, DEPC, and PAO, indicating that the enzyme probably belonged to the subclass of the serine proteases with histidine and cysteine residues essential for catalysis. Furthermore, both enzymes were highly stable over broad temperature (30-80 degrees C), pH (6.0-12.0) and NaCl concentration (2.5-20%) ranges, showing excellent thermostable, alkalistable, and halotolerant nature. The surfactants (SDS, Tween 80, and Triton X-100) did not affect their activities. In addition, both enzymes from LY20 displayed remarkable stability in the presence of water-soluble organic solvents with log P(ow) ( ) <= -0.24. PMID- 22324976 TI - Veterinary and comparative oncology, a decade in cancer research. PMID- 22324977 TI - Comparison of chest radiograph scoring to lung weight as a quantitative index of pulmonary edema in organ donors. AB - Quantification of the degree of pulmonary edema in organ donors is useful for assessing the clinical severity of pulmonary edema, determining response to therapy, and as an endpoint for therapeutic trials. Currently, there is no accurate non-invasive method for assessing the degree of pulmonary edema. We tested the performance of a four-quadrant chest radiographic scoring system compared to quantification of pulmonary edema by excised lung weight in 84 donors whose lungs were not used for transplantation. Chest radiographs were taken 3.6 +/- 3.0 h prior to organ procurement and were scored by two of the authors. Lungs were excised without perfusion and individually weighed. The chest radiographic scoring system had good performance: correlation between total radiographic score and total lung weight of 0.61, p < 0.001. Performance of the scoring system was improved when chest radiographs with atelectasis were excluded (r = 0.79, p < 0.001). The area under the receiver operator characteristic curve for the detection of moderate pulmonary edema (total lung weight >1000 g) was 0.80. This chest radiographic scoring system may potentially be used to assess the clinical severity of pulmonary edema and may be useful as part of the evaluation of donors for suitability for lung transplantation. PMID- 22324978 TI - Silver nanoparticles induce apoptotic cell death in Candida albicans through the increase of hydroxyl radicals. AB - Silver nanoparticles have been shown to be detrimental to fungal cells although the mechanism(s) of action have not been clearly established. In this study, we used Candida albicans cells to show that silver nanoparticles exert their antifungal effect through apoptosis. Many studies have shown that the accumulation of reactive oxygen species induces and regulates the induction of apoptosis. Furthermore, hydroxyl radicals are considered an important component of cell death. Therefore, we assumed that hydroxyl radicals were related to apoptosis and the effect of thiourea as a hydroxyl radical scavenger was investigated. We measured the production of reactive oxygen species and investigated whether silver nanoparticles induced the accumulation of hydroxyl radicals. A reduction in the mitochondrial membrane potential shown by flow cytometry analysis and the release of cytochrome c from mitochondria were also verified. In addition, the apoptotic effects of silver nanoparticles were detected by fluorescence microscopy using other confirmed diagnostic markers of yeast apoptosis including phosphatidylserine externalization, DNA and nuclear fragmentation, and the activation of metacaspases. Cells exposed to silver nanoparticles showed increased reactive oxygen species and hydroxyl radical production. All other phenomena of mitochondrial dysfunction and apoptotic features also appeared. The results indicate that silver nanoparticles possess antifungal effects with apoptotic features and we suggest that the hydroxyl radicals generated by silver nanoparticles have a significant role in mitochondrial dysfunctional apoptosis. PMID- 22324979 TI - Occurrence and complications of tracheal reintubation in critically ill adults. AB - BACKGROUND: Timing and preparation for tracheal extubation are as critical as the initial intubation. There are limited data on specific strategies for a planned extubation. The extent to which the difficult airway at reintubation contributes to patient morbidity is unknown. The aim of the present study was to describe the occurrence and complications of failed extubation and associated risk factors, and to estimate the mortality and morbidity associated with reintubation attempts. METHODS: Cohort study of 2,007 critically ill adult patients admitted to the ICU with an ETT. Patients were classified in 2 groups, based on the requirement for reintubation: "never reintubated" versus ">= 1 reintubations." Baseline characteristics, ICU and hospital stay, hospital mortality, and in patient costs were compared between patients successfully extubated and those with reintubation outside the operating room, using regression techniques. Reasons, airway management techniques, and complications of intubation and reintubation were summarized descriptively. RESULTS: 376 patients (19%) required reintubation, and 230 (11%) were reintubated within 48 hours, primarily due to respiratory failure. Patients requiring reintubation were older, more likely to be male, and had higher admission severity score. Difficult intubation and complications were similar for initial and subsequent intubation. Reintubation was associated with a 5-fold increase in the relative odds of death (adjusted odds ratio 5.86, 95% CI 3.87-8.89, P < .01), and a 2-fold increase in median ICU and hospital stay, and institutional costs. Difficult airway at reintubation was associated with higher mortality (adjusted odds ratio 2.23, 95% CI 1.01-4.93, P = .05). CONCLUSIONS: Nearly 20% of critically ill patients required out of operating room reintubation. Reintubation was associated with higher mortality, stay, and cost. Moreover, a difficult airway at reintubation was associated with higher mortality. PMID- 22324980 TI - Siglec-8 and Siglec-F, the new therapeutic targets in asthma. AB - The recruitment of eosinophils from the circulation into the airway is a prominent feature of allergic asthma. Persistent inflammatory responses may arise from inefficient mechanisms for resolution of inflammation, including delayed apoptosis. Several studies suggest that eosinophil apoptosis is delayed in asthma. Sialic acid-binding immunoglobulin-like lectins are characterized by their sequence similarities and abilities to bind sialic acids in glycoproteins and glycolipids. Siglec-8 is uniquely expressed on eosinophils, mast cells, and basophils. Engagement of Siglec-8 on blood eosinophils results in caspase- and mitochondria-dependent apoptosis. Eosinophil apoptosis is an important therapeutic target for the development of novel anti-asthma treatments that specifically target the eosinophil. PMID- 22324981 TI - Association of dihydrofolate reductase (DHFR) -317AA genotype with poor response to methotrexate in patients with rheumatoid arthritis. AB - OBJECTIVES: Identifying genetic predictors of methotrexate (MTX) treatment response in patients with rheumatoid arthritis (RA) may have great importance for optimising drug doses required for clinical benefit without toxicity. In a group of 125 RA patients treated with MTX we investigated whether selected polymorphisms in genes relevant for MTX action (aminoimidazole-4-carboxiamide ribonucleotide transformylase, ATIC, and dihydrofolate reductase, DHFR) modulate disease activity and/or have impact on therapy side effects. METHODS: The efficacy of treatment was estimated both by the disease activity score in 28 joints (DAS28), based on EULAR criteria, and relative DAS28 (rDAS28) score. Adverse drug events (ADEs) were also recorded. RA patients were genotyped using the PCR-RFLP method, followed by an association study between ATIC -129T>G, DHFR 216T>C and DHFR -317A>G polymorphisms and the efficacy and toxicity of MTX. RESULTS: According to the EULAR response criteria, 96 RA patients (76.8%) were classified as responders (good/moderate response) and 29 (23.2%) as non responders (poor response). rDAS28 values ranged from -0.01 to 0.80 (mean value 0.31+/-0.19). Among 125 patients enrolled in this study 39 experienced at least one side effect. The DHFR -317AA genotype was associated with the less favourable response (reduction in rDAS28 score, p=0.05). None of the analysed polymorphisms was associated with MTX toxicity. CONCLUSIONS: RA patients with DHFR-317AA genotype had less favourable response to MTX. Further studies in larger patient populations are necessary to confirm the relationship between the analysed polymorphisms and MTX treatment response. PMID- 22324982 TI - The International Society of Amyloidosis: brief comments on our symposia and our society. PMID- 22324983 TI - The promise of microbial engineering for developing new strategies for tackling human disease. PMID- 22324984 TI - Antimicrobial resistance in long-term care facilities. PMID- 22324986 TI - New developments in invasive fungal disease. AB - Invasive fungal infections continue to be a major cause of morbidity and mortality in immunocompromised or severely ill patients. This report highlights new research data presented at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy on invasive fungal disease and its treatment. A number of important clinical trials were reported, and there were also interesting presentations on the use of new diagnostic tools, further studies on therapeutic drug monitoring for azoles and updates on several of the emerging fungal pathogens. PMID- 22324987 TI - A coincidence detector triggers botulinum neurotoxin translocation. AB - Botulinum neurotoxins (BoNTs) are the deadliest poisons known to man. They possess a particular duality, rapidly increasing clinical utility for a wide range of disorders and large concern as a possible weapon of bioterrorism. While great strides have been made in the structural and biochemical understanding of the mechanism of intoxication, the specific molecular details behind BoNT translocation out of endosomes remain elusive. In this study, it was conclusively demonstrated that light chain metalloprotease translocation can only occur in the presence of low pH, as is found in endosomes, and GT1b ganglioside coreceptor, whose role was previously thought to only be in cell surface recognition by the toxin. As stated by the authors, the BoNT receptor-binding domain therefore serves as a 'coincidence receptor' in that pH sensing and conformational change to a translocation competent form must be coupled in some way to receptor binding. Further study using atomic force microscopy also suggested the presence of oligomeric toxin channels that can be inhibited by the natural product toosendanin. This data revises the model of BoNT intoxication and demonstrates a mechanism for the amazing temporal and spatial control possessed by this toxin, which ultimately manifests in its extreme potency. PMID- 22324988 TI - Methicillin-resistant Staphylococcus aureus infection is associated with increased mortality. AB - Methicillin resistance is a widespread and major source of treatment complication in Staphylococcus aureus infections. Whether infections with methicillin resistant S. aureus are associated with a worse clinical outcome, such as higher mortality, has remained controversial. Analyzing data from a large, global multicenter study, Hanberger et al. demonstrate that methicillin-resistant S. aureus infections are associated with approximately 50% higher mortality in the intensive care unit and significantly more frequent among critically ill patients than infections with methicillin-susceptible S. aureus. These findings call for the implementation or continuation of active methicillin-resistant S. aureus surveillance measures. PMID- 22324989 TI - Does HPV type 16 or 18 prevalence in cervical intraepithelial neoplasia grade 3 lesions vary by age? An important issue for postvaccination surveillance. AB - AIM: We used existing data to investigate whether prevalence of HPV16/18 in cervical intraepithelial neoplasia 3 (CIN3) varies by age, in order to determine whether age specific baseline data is required as the prevaccination comparator for type-specific surveillance following HPV vaccination programs. MATERIALS & METHODS: We analyzed available Australian HPV typing data from 317 cervical smears from women with concurrent CIN3 on biopsy and conducted a review and analysis of the international literature. RESULTS: Among 317 women with CIN3, HPV16 was detected in 70% of those 16-25 years old, 59% of 26-35-year-olds and 48% of >36-year-olds (p = 0.025). This association took the form of a trend with decreasing HPV16 prevalence with increasing age (p = 0.007). That HPV16 is commoner in younger women with high-grade cervical lesions was consistent with all but one study of 18 identified in the literature. CONCLUSION: In screened populations, younger women with CIN3 are more likely to have HPV16 detected. To make valid pre- and post-vaccination comparisons, surveillance specimens for HPV typing should be both age stratified and lesion specific. PMID- 22324990 TI - A multicenter, open-label study of posaconazole oral suspension in the treatment of invasive fungal infections in patients refractory to or intolerant of first line therapy. AB - AIM: Invasive fungal infections pose a severe health threat to patients. Despite recent advances in drug development, treatment of recurrent fungal infections remains difficult. Posaconazole is a broad-spectrum triazole antifungal drug available for oral administration. Although initial studies have described its use in treating various fungal infections, its efficacy and safety in patients with invasive fungal infections remains to be further confirmed. MATERIALS & METHODS: In this study, we performed a multicenter, open-label clinical trial of posaconazole oral suspension in the treatment of 63 patients with invasive fungal infections who were refractory to or intolerant of first-line therapy. RESULTS: Our result showed that 64.4% of patients had a clinical response after posaconazole treatment, with 52.9% showing eradication of the fungal infection. The treatment caused some adverse effects of mild or moderate severity that were of short duration. CONCLUSION: The results of this trial indicate that posaconazole can be used in invasive fungal infections as an alternative or salvage therapy. PMID- 22324991 TI - Adenovirus degradation of cellular proteins. AB - Eukaryotic cells orchestrate constant synthesis and degradation of intracellular components, including soluble proteins and organelles. The two major intracellular degradation pathways are the ubiquitin/proteasome system and autophagy. Whereas ubiquitin/proteasome system is involved in rapid degradation of proteins, autophagy selectively removes protein aggregates and damaged organelles. Failure of these highly adjusted proteolytic systems to maintain basal turnover leads to altered cellular homeostasis. During evolution, certain viruses have developed mechanisms to exploit their functions to facilitate their own replication, prevent viral clearance and promote the outcome of infection. In this article, we summarize the current opinion on adenoviruses (Ad) and molecular host cell targets, extending on recent evidences for protein degradation pathways in infected cells. We describe recently identified connections between Ad mediated proteolysis and viral replication with main emphasis on the function of certain Ad proteins. PMID- 22324992 TI - Future perspective on host-pathogen interactions during bacterial biofilm formation within the nasopharynx. AB - Nasopharyngeal colonization provides bacteria with a place of residence, a platform for person-to-person transmission and for many opportunistic pathogens it is a prerequisite event towards the development of invasive disease. Therefore, how host factors within the nasopharynx contribute to, inhibit or otherwise shape biofilm formation, the primary mode of existence for colonizing bacteria, and how biofilm bacteria subvert the acute inflammatory response that facilitates clearance, are important topics for future microbiological research. This review proposes the examination of host components as bridging molecules for bacterial interactions during biofilm formation, altered virulence determinant production and cell wall modification as a mechanism for immunoquiescence, and the role of host factors as signals and co-opted mechanisms for bacterial dissemination, together providing an opportunity for disease. PMID- 22324994 TI - Virulence factors involved in the pathogenesis of the infection caused by the swine pathogen and zoonotic agent Streptococcus suis. AB - Streptococcus suis is a major swine pathogen responsible for important economic losses to the swine industry worldwide. It is also an emerging zoonotic agent of meningitis and streptococcal toxic shock-like syndrome. Since the recent recognition of the high prevalence of S. suis human disease in southeast and east Asia, the interest of the scientific community in this pathogen has significantly increased. In the last few years, as a direct consequence of these intensified research efforts, large amounts of data on putative virulence factors have appeared in the literature. Although the presence of some proposed virulence factors does not necessarily define a S. suis strain as being virulent, several cell-associated or secreted factors are clearly important for the pathogenesis of the S. suis infection. In order to cause disease, S. suis must colonize the host, breach epithelial barriers, reach and survive in the bloodstream, invade different organs, and cause exaggerated inflammation. In this review, we discuss the potential contribution of different described S. suis virulence factors at each step of the pathogenesis of the infection. Finally, we briefly discuss other described virulence factors, virulence factor candidates and virulence markers for which a precise role at specific steps of the pathogenesis of the S. suis infection has not yet been clearly established. PMID- 22324993 TI - Bacterial Type IV secretion systems: versatile virulence machines. AB - Many bacterial pathogens employ multicomponent protein complexes to deliver macromolecules directly into their eukaryotic host cell to promote infection. Some Gram-negative pathogens use a versatile Type IV secretion system (T4SS) that can translocate DNA or proteins into host cells. T4SSs represent major bacterial virulence determinants and have recently been the focus of intense research efforts designed to better understand and combat infectious diseases. Interestingly, although the two major classes of T4SSs function in a similar manner to secrete proteins, the translocated 'effectors' vary substantially from one organism to another. In fact, differing effector repertoires likely contribute to organism-specific host cell interactions and disease outcomes. In this review, we discuss the current state of T4SS research, with an emphasis on intracellular bacterial pathogens of humans and the diverse array of translocated effectors used to manipulate host cells. PMID- 22324995 TI - Microcin C: biosynthesis and mechanisms of bacterial resistance. AB - Nonhydrolyzable aminoacyl-adenylates that inhibit protein synthesis provide a promising route towards the development of novel antibiotics whose mechanism of action limits the appearance of bacterial drug resistance. The 'Trojan horse' antibiotic microcin C (McC) consists of a nonhydrolyzable aspartyl-adenylate that is efficiently imported into bacterial cells owing to a covalently attached peptide carrier. Once inside the cell, the carrier is removed by proteolytic processing to release a potent aspartyl tRNA synthetase inhibitor. The focus of this article is on the mechanism of biosynthesis of McC. We also examine the strategies utilized by McC-producing strains to overcome toxicity due to unwanted, premature processing of the drug. This article will discuss how McC biosynthesis can be systematically manipulated for the development of derivatives that will target the entire battery of aminoacyl tRNA synthetases in various bacteria. PMID- 22324996 TI - Cerebral malaria pathogenesis: revisiting parasite and host contributions. AB - Cerebral malaria is one of a number of clinical syndromes associated with infection by human malaria parasites of the genus Plasmodium. The etiology of cerebral malaria derives from sequestration of parasitized red cells in brain microvasculature and is thought to be enhanced by the proinflammatory status of the host and virulence characteristics of the infecting parasite variant. In this article we examine the range of factors thought to influence the development of Plasmodium falciparum cerebral malaria in humans and review the evidence to support their role. PMID- 22324998 TI - Long spin relaxation times in wafer scale epitaxial graphene on SiC(0001). AB - We developed an easy, upscalable process to prepare lateral spin-valve devices on epitaxially grown monolayer graphene on SiC(0001) and perform nonlocal spin transport measurements. We observe the longest spin relaxation times tau(S) in monolayer graphene, while the spin diffusion coefficient D(S) is strongly reduced compared to typical results on exfoliated graphene. The increase of tau(S) is probably related to the changed substrate, while the cause for the small value of D(S) remains an open question. PMID- 22324999 TI - Beneficial regulation of fibrillar collagens, heat shock protein-47, elastin fiber components, transforming growth factor-beta1, vascular endothelial growth factor and oxidative stress effects by copper in dermal fibroblasts. AB - Skin aging is associated with the loss of the structural collagens and the elastin fiber components that form the extracellular matrix (ECM). It is associated with reduced transforming growth factor-beta (TGF-beta), angiogenesis and increased oxidative stress. Copper has been incorporated into cosmetics for anti-skin aging. This research investigated the mechanism for the anti-skin aging effect copper ions, from cuprous oxide powders. Dermal fibroblasts were exposed to copper and examined for expression (protein and/or promoter levels) of types I, III, V collagen, heat shock protein-47 (HSP-47), elastin, fibrillin-1, and fibrillin-2, TGF-beta1, vascular endothelial growth factor (VEGF), and in addition for membrane damage and lipid peroxidation. The direct antioxidant activity of copper was also determined. The research indicates that copper's anti skin aging and skin regeneration potential is through its stimulation of ECM proteins, TGF-beta1, VEGF, and inhibition of oxidative stress effects at physiological concentrations; and supports its use in cosmetics. PMID- 22325000 TI - Susceptibility of the pilot balloon of the disposable laryngeal mask airway to puncture during laser therapy. AB - The tube of the laryngeal mask airway is frequently protected by foil during ablative laser procedures. The pilot balloon, however, is often left exposed. The effect of firing seven different cutaneous lasers at the pilot balloon of a disposable laryngeal mask airway was examined to assess its susceptibility to accidental laser strikes. The time taken for each laser to penetrate the pilot balloon was calculated from an average of five laser strikes. The carbon dioxide and erbium YAG lasers punctured the pilot balloon in a mean (SD) of 0.07 (0.02) s and 0.7 (0.1) s, respectively, with the neodymium YAG laser the next quickest to puncture at 3.3 (1.0) s. All other lasers punctured the pilot balloon in less than 15 s. These data suggest that protection of the pilot balloon of the LMA is necessary when using carbon dioxide and erbium YAG lasers. PMID- 22325001 TI - Elevated anti-tuberculous glycolipid antibody titres in healthy adults and tuberculosis patients in Thailand. AB - OBJECTIVE: To evaluate immunoglobulin G (IgG) and immunoglobulin A (IgA) responses to tuberculous-glycolipid antigen (TBGL-IgG and -IgA) in pulmonary tuberculosis (TB) patients and healthy controls in Thailand. DESIGN: Anti-TBGL antibody titres and other TB related markers were measured in the serum samples of 24 adults with pulmonary TB (PTB), 28 healthy adults (HA), 23 children with TB (CTB) and 24 healthy children (HC). RESULT: Both TBGL-IgG and -IgA titres were significantly higher only in adult PTB cases compared to controls (P < 0.001 for all). TBGL-IgG was highly sensitive (92%) in PTB patients, but frequent positive proportions of TBGL-IgG (46%) and -IgA (36%) in HAs were the cause of low specificities of TBGL-IgG (54%) and -IgA (64%); that of TBGL-IgG+IgA (75%) was the highest. Antibody titres were positively correlated in TBGL-IgG+IgA double positive HAs (HA+, 7/28, P < 0.01), but not in HA- (P > 0.05). Serum IgG and IgA levels were not correlated with TBGL-IgG or -IgA levels (P > 0.05). KL-6 and leptin levels were normal and were not different between HA+ and HA-, indicating absence of active TB in HAs. CONCLUSION: Enhanced TBGL-IgG+IgA responses in HAs could indicate latent TB infection. Careful follow-up studies in HAs could clarify the significance of elevated TBGL antibodies as early disease markers. PMID- 22325002 TI - Validation of an LC-MS/MS method for malachite green (MG), leucomalachite green (LMG), crystal violet (CV) and leucocrystal violet (LCV) residues in fish and shrimp. AB - A quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous analyses of malachite green (MG), crystal violet (CV) and its major metabolites, leucomalachite green (LMG) and leucocrystal violet (LCV) residues in fish and shrimp samples has been validated. Fish and shrimp samples were extracted with citrate buffer/acetonitrile, and the extracts were purified on strong cation-exchange (SCX) solid-phase extraction (SPE) cartridge. After conversion of LMG into MG using a post column oxidation reactor containing lead (IV) oxide (PbO(2)), the effluents were analysed. Residues were analysed using positive-ion electrospray ionisation (ESI). Identification and quantification of analytes were based on the ion transitions monitored by multiple reaction monitoring (MRM). Validation of the method was carried out in accordance with the Decision 2002/657/EC, which establishes criteria and procedures for the validation of methods. The following parameters were determined: decision limit (CCalpha), detection capability (CCbeta), linearity, accuracy, precision, selectivity, specificity and matrix effect. The decision limits (CCalpha) for MG, LMG, CV and LCV were 0.164, 0.161, 0.248 and 0.860 ug kg(-1). The respective detection capabilities (CCbeta) were 0.222, 0.218, 0.355 and 1.162 ug kg(-1). Typical recoveries (intermediate precision) in shrimp, for MG, CV, LMG and LCV for 2.0 ug kg(-1) level fortified samples using the optimised procedure were in the range 69%, 97%, 80.3% and 71.8%, respectively. The findings demonstrate the suitability of the method to detect simultaneously MG, CV and its metabolite (LMG and LCV) in fish and shrimp. PMID- 22325003 TI - Bottom-up effects of species diversity on the functioning and stability of food webs. AB - 1. The importance of species diversity for the stability of populations, communities and ecosystem functions is a central question in ecology. 2. Biodiversity experiments have shown that diversity can impact both the average and variability of stocks and rates at these levels of ecological organization in single trophic-level ecosystems. Whether these impacts hold in food webs and across trophic levels is still unclear. 3. We asked whether resource species diversity, community composition and consumer feeding selectivity in planktonic food webs impact the stability of resource or consumer populations, community biomass and ecosystem functions. We also tested the relative importance of resource diversity and community composition. 4. We found that resource diversity negatively affected resource population stability, but had no effect on consumer population stability, regardless of the consumer's feeding selectivity. Resource diversity had positive effects on most ecosystem functions and their stability, including primary production, resource biomass and particulate carbon, nitrogen and phosphorus concentrations. 5. Community composition, however, generally explained more variance in population, community and ecosystem properties than species diversity per se. This result points to the importance of the outcomes of particular species interactions and individual species' effect traits in determining food web properties and stability. 6. Among the stabilizing mechanisms tested, an increase in the average resource community biomass with increasing resource diversity had the greatest positive impact on stability. 7. Our results indicate that resource diversity and composition are generally important for the functioning and stability of whole food webs, but do not have straightforward impacts on consumer populations. PMID- 22325004 TI - Shewanella bloodstream infection. PMID- 22325005 TI - Non-hispanic whites have higher risk for pulmonary impairment from pulmonary tuberculosis. AB - BACKGROUND: Disparities in outcomes associated with race and ethnicity are well documented for many diseases and patient populations. Tuberculosis (TB) disproportionately affects economically disadvantaged, racial and ethnic minority populations. Pulmonary impairment after tuberculosis (PIAT) contributes heavily to the societal burden of TB. Individual impacts associated with PIAT may vary by race/ethnicity or socioeconomic status. METHODS: We analyzed the pulmonary function of 320 prospectively identified patients with pulmonary tuberculosis who had completed at least 20 weeks standard anti-TB regimes by directly observed therapy. We compared frequency and severity of spirometry-defined PIAT in groups stratified by demographics, pulmonary risk factors, and race/ethnicity, and examined clinical correlates to pulmonary function deficits. RESULTS: Pulmonary impairment after tuberculosis was identified in 71% of non-Hispanic Whites, 58% of non-Hispanic Blacks, 49% of Asians and 32% of Hispanics (p < 0.001). Predictors for PIAT varied between race/ethnicity. PIAT was evenly distributed across all levels of socioeconomic status suggesting that PIAT and socioeconomic status are not related. PIAT and its severity were significantly associated with abnormal chest x-ray, p < 0.0001. There was no association between race/ethnicity and time to beginning TB treatment, p = 0.978. CONCLUSIONS: Despite controlling for cigarette smoking, socioeconomic status and time to beginning TB treatment, non-Hispanic White race/ethnicity remained an independent predictor for disproportionately frequent and severe pulmonary impairment after tuberculosis relative to other race/ethnic groups. Since race/ethnicity was self reported and that race is not a biological construct: these findings must be interpreted with caution. However, because race/ethnicity is a proxy for several other unmeasured host, pathogen or environment factors that may contribute to disparate health outcomes, these results are meant to suggest hypotheses for further research. PMID- 22325006 TI - Freezing fecal samples prior to DNA extraction affects the Firmicutes to Bacteroidetes ratio determined by downstream quantitative PCR analysis. AB - Freezing stool samples prior to DNA extraction and downstream analysis is widely used in metagenomic studies of the human microbiota but may affect the inferred community composition. In this study, DNA was extracted either directly or following freeze storage of three homogenized human fecal samples using three different extraction methods. No consistent differences were observed in DNA yields between extractions on fresh and frozen samples; however, differences were observed between extraction methods. Quantitative PCR analysis was subsequently performed on all DNA samples using six different primer pairs targeting 16S rRNA genes of significant bacterial groups, and the community composition was evaluated by comparing specific ratios of the calculated abundances. In seven of nine cases, the Firmicutes to Bacteroidetes 16S rRNA gene ratio was significantly higher in fecal samples that had been frozen compared to identical samples that had not. This effect was further supported by qPCR analysis of bacterial groups within these two phyla. The results demonstrate that storage conditions of fecal samples may adversely affect the determined Firmicutes to Bacteroidetes ratio, which is a frequently used biomarker in gut microbiology. PMID- 22325007 TI - Effect of Ca2+ on the microtubule-severing enzyme p60-katanin. Insight into the substrate-dependent activation mechanism. AB - Katanin p60 (p60-katanin) is a microtubule (MT)-severing enzyme and its activity is regulated by the p80 subunit (adaptor-p80). p60-katanin consists of an N terminal domain, followed by a single ATPase associated with various cellular activities (AAA) domain. We have previously shown that the N-terminal domain serves as the binding site for MT, the substrate of p60-katanin. In this study, we show that the same domain shares another interface with the C-terminal domain of adaptor-p80. We further show that Ca(2+) ions inhibit the MT-severing activity of p60-katanin, whereas the MT-binding activity is preserved in the presence of Ca(2+). In detail, the basal ATPase activity of p60-katanin is stimulated twofold by both MTs and the C-terminal domain of adaptor-p80, whereas Ca(2+) reduces elevated ATPase activity to the basal level. We identify the Ca(2+) -binding site at the end of helix 2 of the N-terminal domain, which is different from the MT binding interface. On the basis of these observations, we propose a speculative model in which spatial rearrangement of the N-terminal domain relative to the C terminal AAA domain may be important for productive ATP hydrolysis towards MT severing. Our model can explain how Ca(2+) regulates both severing and ATP hydrolysis activity, because the Ca(2+) -binding site on the N-terminal domain moves close to the AAA domain during MT severing. PMID- 22325008 TI - Elevated interleukin-8 enhances prefrontal synaptic transmission in mice with persistent inflammatory pain. AB - BACKGROUND: Interleukin-8 (IL-8) is known for its roles in inflammation and plays critical roles in the development of pain. Its expression increases in the brain after peripheral inflammation. Prefrontal cortex, including the anterior cingulate cortex (ACC), is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission, however, little is known about the expression of IL-8 and its role in the enhanced ACC synaptic transmission in animals with persistent inflammatory pain. FINDINGS: In the present study, we examined IL-8 expression in the ACC, somatosensory cortex (SSC), and the dorsal horn of lumbar spinal cord following hind-paw administration of complete Freund's adjuvant (CFA) in mice and its effects on the ACC synaptic transmission. Quantification of IL-8 at protein level (by ELISA) revealed enhanced expression in the ACC and spinal cord during the chronic phases of CFA-induced peripheral inflammation. In vitro whole-cell patch clamp recordings revealed that IL-8 significantly enhanced synaptic transmission through increased probability of neurotransmitter release in the ACC slice. ACC local infusion of repertaxin, a non-competitive allosteric blocker of IL-8 receptors, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in mice. CONCLUSIONS: Our findings suggest that up-regulation of IL-8 in the ACC partly attributable to the enhanced prefrontal synaptic transmission in the mice with persistent inflammatory pain. PMID- 22325009 TI - Can we depend on case management to prevent re-establishment of P. falciparum malaria, after local interruption of transmission? AB - Recent declines in malaria burden in many parts of the world have prompted consideration of how interruption of Plasmodium falciparum transmission could be maintained, if achieved, and notably whether large-scale vector control could be replaced with surveillance. This information is essential for elimination feasibility assessments and planning. The risk of re-establishment of transmission depends mainly on vectorial capacity (receptivity), likely to rebound once vector control is removed, the rate of importation of infections (vulnerability), the capacity to detect and treat infections and the level of immunity in infected individuals. Timely detection and removal of new infections is likely to be critical to prevent re-establishment of transmission. We assess, through mathematical modeling and simulation, which levels of case detection and treatment (case management) are required to prevent re-establishment of transmission of P. falciparum after local interruption of transmission has been achieved, in settings with varying receptivity and vulnerability. We find that, even at rather low levels of receptivity, case management alone cannot reliably prevent re-establishment of P. falciparum malaria transmission in the face of medium to high importation rates. Thus, if vector control is to be discontinued, preventing the importations by controlling transmission in source areas will generally be necessary for preventing reintroduction in such settings, and cannot be substituted by very high levels of case management coverage. PMID- 22325010 TI - A new approach to characterising infectious disease transmission dynamics from sentinel surveillance: application to the Italian 2009-2010 A/H1N1 influenza pandemic. AB - Syndromic and virological data are routinely collected by many countries and are often the only information available in real time. The analysis of surveillance data poses many statistical challenges that have not yet been addressed. For instance, the fraction of cases that seek healthcare and are thus detected is often unknown. Here, we propose a general statistical framework that explicitly takes into account the way the surveillance data are generated. Our approach couples a deterministic mathematical model with a statistical description of the reporting process and is applied to surveillance data collected in Italy during the 2009-2010 A/H1N1 influenza pandemic. We estimate that the reproduction number R was initially into the range 1.2-1.4 and that case detection in children was significantly higher than in adults. According to the best fit models, we estimate that school-age children experienced the highest infection rate overall. In terms of both estimated peak-incidence and overall attack rate, according to the Susceptibility and Immunity models the 5-14 years age-class was about 5 times more infected than the 65+ years old age-group and about twice more than the 15 64 years age-class. The multiplying factors are doubled using the Baseline model. Overall, the estimated attack rate was about 16% according to the Baseline model and 30% according to the Susceptibility and Immunity models. PMID- 22325011 TI - Critical immune and vaccination thresholds for determining multiple influenza epidemic waves. AB - Previous influenza pandemics (1918, 1957, and 1968) have all had multiple waves. The 2009 pandemic influenza A (H1N1) (pandemic H1N1) started in April 2009 and was followed, in the United States (US) and temperate Northern Hemisphere, by a second wave during the fall of 2009. The ratio of susceptible and immune individuals in a population at the end of a wave determines the potential and magnitude of a subsequent wave. As influenza vaccines are not completely protective, there was a combined immunity in the population at the beginning of 2010 (due to vaccination and due to previous natural infection), and it was uncertain if this mixture of herd immunity was enough to prevent a third wave of pandemic influenza during the winter of 2010. Motivated by this problem, we developed a mathematical deterministic two-group epidemic model with vaccination and calibrated it for the 2009 pandemic H1N1. Then, applying methods from mathematical epidemiology we developed a scheme that allowed us to determine critical thresholds for vaccine-induced and natural immunity that would prevent the spread of influenza. Finally, we estimated the level of combined immunity in the US during winter 2010. Our results suggest that a third wave was unlikely if the basic reproduction number R(0) were below 1.6, plausible if the original R(0) was 1.6, and likely if the original R(0) was 1.8 or higher. Given that the estimates for the basic reproduction number for pandemic influenza place it in the range between 1.4 and 1.6 (Bacaer and Ait Dads, 2011; Fraser et al., 2009; Munayco et al., 2009; Pourbohloul et al., 2009; Tuite et al., 2010; White et al., 2009; Yang et al., 2009), our approach accurately predicted the absence of a third wave of influenza in the US during the winter of 2010. We also used this scheme to accurately predict the second wave of pandemic influenza in London and the West Midlands, UK during the fall of 2009. PMID- 22325012 TI - The role of aquatic reservoir fluctuations in long-term cholera patterns. AB - We propose and analyze an important extension of standard cholera epidemiological models, explicitly accounting for fluctuations of water availability to the human community under study. The seasonality of water input in the reservoir drives the variation of concentration of Vibrio cholerae. Two compartments are added to the Susceptible-Infected-Bacteria model. First, the recovered individuals, which, over many seasons, lose their immunity to the disease and replenish the Susceptible group. Second, the water volume of the reservoir, which determines bacterial dilution and, consequently, the probability of contracting cholera by ingesting contaminated water. By forcing the model with a seasonally varying hydrologic input, we obtain simulations that can be compared to available data for various regions of the World characterized by different hydrological and epidemiological regimes. The model is shown to satisfactorily reproduce important characteristics of disease insurgence and long-term persistence. Using bifurcation analysis of nonlinear systems, we also explore how different degrees of seasonality and values of the basic reproductive number can change the expected long-term epidemiological time series. We find that there exist parametric conditions where the model shows chaotic patterns - i.e. high unpredictability especially in the amplitude of prevalence peaks - which very much resemble actual data on long-term cholera insurgence. PMID- 22325013 TI - The protective effects of temporary immunity under imposed infection pressure. AB - The aim of this paper is to show in explicit detail that, due to the effects of waning and boosting of immunity, an increasing force of infection does not necessarily lead to an increase in the incidence of disease. Under certain conditions, a decrease of the force of infection may in fact lead to an increase of the incidence of disease. Thus we confirm and reinforce the conclusions from Aguas et al. (2006), concerning pertussis. We do so, however, in the context of Campylobacter infections in humans deriving from animal reservoirs. For such an externally 'driven' epidemic we can ignore the transmission feedback cycle and treat the force of infection as a parameter. As this parameter is, to a certain extent, under public health control, our findings constitute an important warning: reducing exposure may not necessarily lead to a reduction in the occurrence of clinical illness. In a second part of the paper we relate the model parameters to the available data concerning campylobacteriosis. PMID- 22325014 TI - Modelling HIV in the injecting drug user population and the male homosexual population in a developed country context. AB - In many high income countries men who have sex with men (MSM) and injecting drug users (IDUs) are the two groups with the highest HIV prevalence. Yet these two groups are not mutually exclusive, and those MSM who are also IDUs (MSM-IDUs) may be particularly vulnerable to HIV infection. This may be particularly relevant to the IDU population in countries, like the UK, with a much lower HIV prevalence amongst IDUs than MSM, as the MSM-IDUs could provide a route of HIV infection into the IDU population. In this research two alternative modelling approaches that describe the transmission dynamics of HIV within the IDU, MSM, and heterosexual populations are proposed. These models are constructed with two aims. The first is to investigate the possible impact of interventions that target HIV transmission in the MSM and IDU populations, and the second aim is to investigate the impact of the model structure on the model results. An examination of the assortativity of mixing between risk groups is also undertaken. The models are parameterised for England and Wales. While the MSM-IDU population is small, targeting MSM-IDUs was the most efficient intervention strategy in terms of cases averted per 100 individuals targeted with the intervention. Sensitivity analysis showed that variations in the assumed assortativity of mixing between the population groups in both models have a large impact on model results. This means that to generate quantitatively robust estimates for the impact of different intervention strategies it will be necessary to obtain estimates for assortativity values through empirical work. PMID- 22325016 TI - Development of the Rheumatic Disease Illness Perception Questionnaire (RD-IPQ) reliability, validity and responsiveness. PMID- 22325017 TI - Ultra-trace level analysis of morpholine, cyclohexylamine, and diethylaminoethanol in steam condensate by gas chromatography with multi-mode inlet, and flame ionization detection. AB - Steam condensate water treatment is a vital and integral part of the overall cooling water treatment process. Steam condensate often contains varying levels of carbon dioxide and oxygen which acts as an oxidizer. Carbon dioxide forms corrosive carbonic acid when dissolved in condensed steam. To neutralize the harmful effect of the carbonic acid, volatile amine compounds such as morpholine, cyclohexylamine, and diethylaminoethanol are often employed as part of a strategy to control corrosion in the water treatment process. Due to the high stability of these compounds in a water matrix, the indirect addition of such chemicals into the process via steam condensate often results in their presence throughout the process and even into the final product. It is therefore important to understand the impact of these chemicals and their fate within a chemical plant. The ability to analyze such compounds by gas chromatography has historically been difficult due to the lack of chromatographic system inertness at the trace level concentrations especially in an aqueous matrix. Here a highly sensitive, practical, and reliable gas chromatographic approach is described for the determination of morpholine, cyclohexylamine, and diethylaminoethanol in steam condensate at the part-per-billion (ppb) levels. The approach does not require any sample enrichment or derivatization. The technique employs a multi-mode inlet operating in pulsed splitless mode with programmed inlet temperature for sample introduction, an inert base-deactivated capillary column for solute separation and flame ionization detection. Chromatographic performance was further enhanced by the incorporation of 2-propanol as a co-solvent. Detection limits for morpholine, cyclohexylamine, diethylaminoethanol were established to be 100 ppb (v/v), with relative standard deviations (RSD) of less than 6% at the 95% confidence level (n=20) and a percent recovery of 96% or higher for the solutes of interest over a range of 0.1-100 ppm (v/v). A complete analysis can be conducted in less than 10 min. PMID- 22325018 TI - Salt effects on solvent features of coexisting phases in aqueous polymer/polymer two-phase systems. AB - The solvatochromic parameters characterizing the solvent dipolarity/polarizability (pi*), solvent hydrogen-bond donor acidity (alpha), and solvent hydrogen-bond acceptor basicity (beta) of aqueous media were measured in the coexisting phases of aqueous Dextran-Ficoll, Dextran-Ucon, Dextran-PEG, PEG Ucon, Ficoll-Ucon, and Ficoll-PEG two-phase systems (ATPS). Ionic composition of each ATPS included 0.15M KCl, 0.15M KBr, 0.15M NaBr, 0.1M Na(2)SO(4), and 0.1M Li(2)SO(4) in 0.01 M sodium phosphate buffer (NaPB), pH 7.4; and 0.01 M and 0.11 M sodium phosphate buffer, pH 7.4. Partition ratios of sodium salts of dinitrophenylated (DNP) amino acids with aliphatic side-chains (glycine, alanine, norvaline, norleucine, and alpha-amino-n-caprylic acid) were measured in all ATPSs, and the results were evaluated in terms of the differences between the relative hydrophobicity (parameter E) and the electrostatic properties (parameter C) of the aqueous media of the coexisting phases. It was established that parameter E is described by a linear combination of the differences between the solvent dipolarity/polarizability (Deltapi*) and between the solvent hydrogen bond acidity (Deltaalpha) of the media in the coexisting phases. Parameter C depends on the phase forming polymer pair and is shown to be described by a linear combination of three parameters: the differences between the solvent hydrogen-bond acidity (Deltaalpha) and between the solvent hydrogen-bond basicity (Deltabeta) of the media in the coexisting phases, and a measure of the effect of a given salt additive on the hydrogen bonds in water. This effect was represented by a parameter (K(b-l)), characterizing the equilibrium between populations of hydrogen bonds with a bent hydrogen bond conformation and with linear hydrogen bond conformation affected by a given salt additive. PMID- 22325019 TI - Mixed-mode solid-phase extraction followed by dispersive liquid-liquid microextraction for the sensitive determination of ethylphenols in red wines. AB - Selectivity of mixed-mode solid-phase extraction (SPE) was combined with the concentration power of dispersive liquid-liquid microextraction (DLLME) to obtain a sensitive, low solvent consumption method for gas chromatography-mass spectrometry determination of ethylphenol off-flavours (4-ethylphenol, EP; 4 ethylguaicol, EG and 4-ethylcathecol, EC) in complex red wine samples. Under optimized conditions, limits of quantification (LOQs) between 0.3 and 0.8 ng mL( 1) were obtained using just 5 mL of wine and 0.06 mL of 1,1,1-trichloroethane (TCE) as extractant in the DLLME step. Analytes were acetylated after SPE and previously to DLLME concentration to enhance the performance of their GC-MS determination. The overall extraction efficiency of the method was unaffected by the particular characteristics of each wine; thus, accurate results (relative recoveries from 89 to 109% for samples spiked at concentrations from 20 to 1000 ng mL(-1)) were obtained using matrix-matched standards, without requiring the use of the time consuming standard addition quantification methodology. The applicability of the method was demonstrated with the analysis of different red wines. Analytes concentrations varied from 6 to 2265 ng mL(-1) (EP), 0.8 to 251 ng mL(-1) (EG) and non-detected to 158 ng mL(-1) (EC). PMID- 22325020 TI - [Answer to reflections on the "Feasibility of chorionic villus sampling outside referral diagnosis centers"]. PMID- 22325021 TI - Violence and Power. PMID- 22325022 TI - Water development projects and marital violence: experiences from rural Bangladesh. AB - In this study, we explored the implications of a groundwater development project on women's workload and their experience of marital violence in a Bangladesh village. We believe that the project facilitated irrigation water but also that it resulted in seasonal domestic water shortages. Men used deep motorized pumps for irrigation, and women used shallow handpumps for domestic purposes. Many handpumps dried out, so women had to walk to distant wells. This increased their workload and challenged their possibilities of fulfilling household obligations, thereby increasing the risk of normative marital male violence against women as a punishment for their failure. PMID- 22325023 TI - Psychological outcomes of intimate partner violence experienced by Jordanian working women. AB - This study aimed at investigating psychological health problems experienced by working women as a result of their experiences of intimate partner violence (IPV). One hundred one working women participated in the study. Results indicated that nearly half of the participants reported partner violence. Compared with nonabused women, abused women showed significantly higher levels of depressive symptoms (t (78) = -3.4, p = .001) and stress (t (93) = -4.8, p < .0001), while self-esteem did not differ significantly between the two groups. Acknowledgment of this problem and early recognition of the victims may result in improving the health of working women in Jordan. PMID- 22325024 TI - Seizing an opportunity to help-knowledge and attitudes of doctors and nurses toward women victimized by intimate partner violence in Brazil. AB - In this study we combined quantitative (questionnaire survey of 221 health care professionals [HCPs]) and qualitative (interviews with 14 doctors) methods to explore knowledge and attitudes toward health service assistance for women victims of intimate partner violence (IPV). Data were collected in Ribeirao Preto, Brazil, in 2007. We found that most HCPs presented good knowledge of definitions of gender violence, but they had low awareness of its local prevalence, sympathetic attitudes to such women, but highlighted a range of barriers to assisting them. We analyzed these findings in relation to sex, age, profession, and years of experience. PMID- 22325025 TI - Provider barriers and facilitators to screening for intimate partner violence in Bogota, Colombia. AB - We conducted interviews with 27 health care personnel in Bogota, Colombia, to examine provider barriers and facilitators to screening for intimate partner violence (IPV). We used systematic qualitative analysis to identify the range and consistency of beliefs. We found that respondents did not routinely screen for IPV. Providers listed numerous barriers to screening. Ways to improve screening included increased clinician training, installing systematic IPV screening, providing patient education, and implementing health care setting interventions. Improving the care for IPV survivors will involve translating health care personnel preferred solutions into more systematic IPV screening interventions. PMID- 22325026 TI - Violence in the massage parlor industry: experiences of Canadian-born and immigrant women. AB - We examined and contrasted 129 Canadian-born and immigrant women's experiences of violence and associated structural and interpersonal factors within indoor commercial sex venues. The majority experienced at least one form of structural, interpersonal, or both types of violence, with the attempted removal of a condom during sexual services being cited most frequently. Canadian-born women reported more frequent violent assaults in the survey data. The women's qualitative narratives illustrated that perceptions of violence differed significantly among Canadian versus non-Canadian born women. Findings concerning racialization and gendered relations of power have important implications for prevention and interventions to support victims of abuse. PMID- 22325027 TI - Domestic violence among Iraqi refugees in Syria. AB - A domestic violence questionnaire was administered to 701 adult females in a sample of 813 Iraqi households in Syria; unmarried women and women whose husbands were away were excluded, yielding a final sample of 486. Lifetime physical, verbal, or emotional abuse was reported by 30%, and approximately 20% experienced abuse within the past year. Non-Damascus residence, children <18 years in the household, no financial challenges upon arrival, and borrowing money in Syria were associated with increased risk of domestic violence within the past year. Support services are inadequate and should be expanded; and longer-term prevention measures also should be implemented. PMID- 22325029 TI - Effect of functional shift of the mandible on lubrication of the temporomandibular joint. AB - Lubrication of synovial joints reduces the coefficient of friction of the articular cartilage surface. To investigate the effect of malocclusion on the lubrication of the temporomandibular joint (TMJ), we evaluated lubricin expression in the rat TMJ immunohistochemically, under conditions of functional lateral shift of the mandible, during period of growth. Thirty 5-week-old male Wistar rats were divided into experimental, recovery, and control groups. Each rt in the experimental and recovery groups was fitted with an acrylic-plate guiding appliance. The rats in the experimental and control groups were killed at 14 and 28 days after the appliance was attached. Each rat in the recovery group was detached from the appliance at 14 days, and was killed 14 days after the appliance was removed. In the experimental group, the expression of lubricin staining in TMJ cartilage was significantly decreased during the experimental period. In the recovery group, the expression of lubricin staining in TMJ cartilage was significantly greater than in the experimental group, and there was no significant difference at 28 days between the control and recovery groups. Analysis of these data suggests that a functional lateral shift of the mandible during the growth period influences lubrication of the TMJ. PMID- 22325030 TI - Molecular mechanisms of viral inhibitors of RIG-I-like receptors. AB - Activation of innate immune signaling pathways through cytosolic RIG-I-like receptors (RLR) is a crucial response that is antagonized by many viruses. A variety of RNA-related pathogen-associated molecular patterns (PAMPS) have been identified and their role in RLR activation has been examined. Recent studies suggest that several virus-encoded components that antagonize RLR signaling interact with and inhibit the interferon (IFN)-alpha/beta activation pathway using both RNA-dependent and RNA-independent mechanisms. The structural basis for these RLR inhibitory mechanisms, as well as the multifunctional nature of viral RLR antagonists, is reviewed in the context of recent biochemical and structural studies. PMID- 22325032 TI - Diabetes MILES--Australia (management and impact for long-term empowerment and success): methods and sample characteristics of a national survey of the psychological aspects of living with type 1 or type 2 diabetes in Australian adults. AB - BACKGROUND: Successful management of diabetes requires attention to the behavioural, psychological and social aspects of this progressive condition. The Diabetes MILES (Management and Impact for Long-term Empowerment and Success) Study is an international collaborative. Diabetes MILES--Australia, the first Diabetes MILES initiative to be undertaken, was a national survey of adults living with type 1 or type 2 diabetes in Australia. The aim of this study was to gather data that will provide insights into how Australians manage their diabetes, the support they receive and the impact of diabetes on their lives, as well as to use the data to validate new diabetes outcome measures. METHODS/DESIGN: The survey was designed to include a core set of self-report measures, as well as modules specific to diabetes type or management regimens. Other measures or items were included in only half of the surveys. Cognitive debriefing interviews with 20 participants ensured the survey content was relevant and easily understood. In July 2011, the survey was posted to 15,000 adults (aged 18-70 years) with type 1 or type 2 diabetes selected randomly from the National Diabetes Services Scheme (NDSS) database. An online version of the survey was advertised nationally. A total of 3,338 eligible Australians took part; most (70.4%) completed the postal survey. Respondents of both diabetes types and genders, and of all ages, were adequately represented in both the postal and online survey sub-samples. More people with type 2 diabetes than type 1 diabetes took part in Diabetes MILES--Australia (58.8% versus 41.2%). Most respondents spoke English as their main language, were married/in a de facto relationship, had at least a high school education, were occupied in paid work, had an annual household income > $AUS40,000, and lived in metropolitan areas. DISCUSSION: A potential limitation of the study is the under-representation of respondents from culturally and linguistically diverse backgrounds (including Aboriginal and Torres Strait Islander origin). Diabetes MILES--Australia represents a major achievement in the study of diabetes in Australia, where for the first time, the focus is on psychosocial and behavioural aspects of this condition at a national level. PMID- 22325033 TI - Macrocytosis is a predictor of resting lactate concentrations in persons on dideoxynucleoside therapy for HIV infection. AB - OBJECTIVES: Mitochondrial toxicity is an important toxicity of antiretroviral therapy and may manifest as elevated blood lactate. Macrocytosis has been hypothesized to act as a marker of mitochondrial toxicity in persons with HIV infection. As part of a larger study on markers of mitochondrial toxicity we evaluated the relationship between resting lactate and erythrocyte mean corpuscular volume (MCV). METHODS: We studied the effect of micronutrient supplementation on lactate metabolism in three groups: those with HIV on and not on dideoxynucleoside-containing antiretroviral therapy and those without HIV. As part of the study we measured resting lactate and erythrocyte MCV after a 14-h fast. RESULTS: Erythrocyte MCV was significantly higher among the 11 participants on antiviral therapy (109.3 femtoliters (fl)) compared to five controls without HIV (89.3 fl) and four controls with HIV not on antiviral therapy (88.3 fl). In addition a strong predictive relationship was seen between MCV and resting lactate (R(2)=0.548, p<0.01). CONCLUSIONS: Macrocytosis may be a marker of treatment-related mitochondrial dysfunction in persons on treatment for HIV. Evaluating patients for early evidence of mitochondrial dysfunction in resource constrained settings could be facilitated by this marker. PMID- 22325031 TI - GB virus C: the good boy virus? AB - GB virus C (GBV-C) is a lymphotropic human virus discovered in 1995 that is related to hepatitis C virus (HCV). GBV-C infection has not been convincingly associated with any disease; however, several studies found an association between persistent GBV-C infection and improved survival in HIV-positive individuals. GBV-C infection modestly alters T cell homeostasis in vivo through various mechanisms, including modulation of chemokine and cytokine release and receptor expression, and by diminution of T cell activation, proliferation and apoptosis, all of which may contribute to improved HIV clinical outcomes. In vitro studies confirm these clinical observations and demonstrate an anti-HIV replication effect of GBV-C. This review summarizes existing data on potential mechanisms by which GBV-C interferes with HIV, and the research needed to capitalize on this epidemiological observation. PMID- 22325034 TI - Cytokine and chemokine responses to Japanese encephalitis live attenuated vaccine in a human population. AB - OBJECTIVES: The SA14-14-2 Japanese encephalitis (JE) live attenuated vaccine is licensed for use only in China, and has provided excellent efficacy in reducing the incidence of JE. The humoral immune response related to the JE vaccination has been well characterized, however cellular immune responses are less well known. METHODS: Thirty-four healthy males who had recently received inoculation with the SA14-14-2 live attenuated vaccine were recruited. Serum samples from these subjects were analyzed for cytokine and chemokine levels using the FlowCytomix method. RESULTS: Eighteen of 34 subjects were positive for JE virus specific IgG antibodies. Levels of interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta were significantly higher in the vaccinees than in a control group (p<0.0001, p<0.0001, p=0.021, and p<0.0001, respectively). IL-6 was detectable in 64.7% of vaccinees, but was not detectable in any of the controls. IL-1beta, IL-2, IL-4, IL-5, IL-9, IL-10, IL-12p70, IL-13, IL-17A, IL-22, tumor necrosis factor (TNF) alpha, and interferon (IFN)-gamma were detected in very few subjects or were undetectable in both groups. CONCLUSIONS: IL-6, IL-8, MCP-1, MIP-1alpha, and MIP 1beta may play important roles in the immune response to JE live attenuated vaccine. PMID- 22325035 TI - Circulating selenium and carboxymethyl-lysine, an advanced glycation endproduct, are independent predictors of anemia in older community-dwelling adults. AB - OBJECTIVE: To assess whether selenium and carboxymethyl-lysine (CML), two biomarkers of oxidative stress, are independent predictors of anemia in older community-dwelling adults. METHODS: Plasma levels of selenium, CML, folate, vitamin B12, and testosterone and markers of iron status and inflammation were measured at baseline in 1036 adults at least 65 y old in the Invecchiare in Chianti Study, a population-based cohort study of aging in Tuscany, Italy, and examined in relation to prevalent anemia and incident anemia over 6 y of follow up. RESULTS: At enrollment, 11.6% of participants were anemic. Of 472 participants who were non-anemic at enrollment, 72 (15.3%) developed anemia within 6 y of follow-up. At enrollment, plasma CML in the highest quartile (>425 ng/mL) and plasma selenium in the lowest quartile (<66.6 MUg/L) predicted incident anemia (hazard ratio 1.67, 95% confidence interval 1.07-2.59, P = 0.02; hazard ratio 1.55, 95% confidence interval 1.01-2.38, P = 0.05, respectively) in a multivariate Cox proportional hazards model that adjusted for age, education, body mass index, cognition, inflammation, red blood cell distribution width, ferritin, vitamin B12, testosterone, and chronic diseases. CONCLUSION: Elevated plasma CML and low plasma selenium are long-term independent predictors of anemia in older community-dwelling adults. These findings support the idea that oxidative stress contributes to the development of anemia. PMID- 22325037 TI - Spatio-temporal patterns of habitat use in voles and shrews modified by density, season and predators. AB - 1. Although the intrinsic habitat preferences of a species can be considered to be fixed, the realized habitat use depends on the prevailing abiotic and biotic conditions. Often the core habitats are occupied by dense and stable populations, while marginal habitats become occupied only at times of high density. In a community of interacting species, habitat uses of different species become inter related, for example an increased density of a strong competitor forcing a weaker competitor to use more marginal habitats. 2. We studied the spatio-temporal distribution patterns of three common small mammal species, the bank vole Myodes glareolus; the field vole Microtus agrestis; and the common shrew Sorex araneus, in a 4-year trapping study carried out on six large islands, each containing a mixture of three main habitat types (forest, field and clear-cut). We experimentally released least weasels (Mustela n. nivalis) to some of the islands to see how the focal species respond to increased predation pressure. 3. Both vole species were largely restricted to their core habitats (bank voles to forests and field voles to fields) at times of low population density. With increasing density, the relative habitat use of both species increased in the clear-cut areas. The common shrew was a generalist in its habitat use at all population densities. 4. The release of the weasels changed the habitat use of all study species. 5. The vole species showed a stronger aggregated pattern than the common shrew, especially at low population density. The vole aggregations remained in the same localities between seasons, except in the case of bank voles after the weasels were released. 6. Bank voles and field voles avoided each other at high density. 7. We conclude that intrinsically differential habitat requirements and flexibility to modify habitat use facilitate the coexistence of the two competing vole species in mosaic landscapes consisting of boreal forests and open habitats. PMID- 22325036 TI - Distinct overlapping sequences at the carboxy-terminus of merlin regulate its tumour suppressor and morphogenic activity. AB - The Neurofibromatosis 2 (NF2) gene product merlin is a tumour suppressor, which in addition to inhibiting cell proliferation regulates cell morphology. The morphogenic properties of merlin may play a role in tumour suppression, as patient-derived tumour cells demonstrate cytoskeletal abnormalities. However, it is still unclear how these functions are linked. The N-terminal FERM-domain of merlin is highly homologous to the oncogenic protein ezrin, while the C-termini are less conserved, suggesting that the opposite effect of the proteins on proliferation could be mediated by their distinct C-terminal regions. In this study we characterize the role of the most C-terminal residues of merlin in the regulation of proliferation, cytoskeletal organization, phosphorylation and intramolecular associations. In addition to the two full-length merlin isoforms and truncating mutations found in patients, we focused on the evolutionally conserved C-terminal residues 545-547, also harbouring disease-causing mutations. We demonstrate that merlin induces cell extensions, which result from impaired retraction of protrusions rather than from increased formation of filopodia. The residues 538-568 were found particularly important for this morphogenic activity. The results further show that both merlin isoforms are able to equally inhibit proliferation, whereas C-terminal mutants affecting residues 545-547 are less effective in growth suppression. This study demonstrates that the C-terminus contains distinct but overlapping functional domains important for regulation of the morphogenic activity, intramolecular associations and cell proliferation. PMID- 22325038 TI - Effect of piracetam and vitamin E on phosphamidon-induced impairment of memory and oxidative stress in rats. AB - Organophosphate pesticides, such as phosphamidon (PHOS), have been shown to adversely affect memory and induce oxidative stress after both acute and chronic exposure. The present study was therefore designed to investigate the effects of piracetam (PIR) and vitamin E on PHOS-induced modulation of cognitive function and oxidative stress in rats. Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining the levels of malondialdehyde (MDA) and nonprotein thiols (NP-SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and a prolongation of TL in the PHOS (1.74 mg/kg/day per oral; p.o.)-treated group at weeks 6 and 8, as compared to the control group. Administration of PIR (600 mg/kg/day p.o.) or vitamin E (125 mg/kg/day p.o.) for 2 weeks antagonized the effect of PHOS on SDL as well as TL. PHOS per se produced a significant increase in brain MDA levels and a decrease in brain NP-SH levels, whereas administration of PIR (600 mg/kg/day p.o.) or vitamin E (125 mg/kg/day p.o.) attenuated these effects. Thus, the results of the study showed that both PIR and vitamin E attenuated the cognitive dysfunction and oxidative stress induced by PHOS in the rat brain. PMID- 22325039 TI - Insulin and hypertonic glucose in the management of aseptic fat liquefaction of post-surgical incision: a meta-analysis and systematic review. AB - A meta-analysis and systematic review assessing randomised controlled trials (RCTs) was sought to determine whether subcutaneous injection of insulin with hypertonic glucose promotes healing in postoperative incisions with aseptic fat liquefaction. We searched the Cochrane library, Pubmed, EMBASE, National Science Digital Library (NSDL) and China Biological Medicine Database (CBMdisc) for literature published from 1 January 1990 to 30 September 2011. RCTs that evaluated subcutaneous injection of insulin with hypertonic glucose as a treatment for postoperative wound with fat liquefaction were sought. Wound healing was the primary endpoint. Jadad score and Cochrane Collaboration's tool were used for assessing quality of studies and risk of bias. We abstracted data regarding time to wound healing, cost and adverse effects. The random-effects inverse variance model was used for all analyses using weighted mean difference and 95% confidence interval. Eight trials (414 participants) were identified that met the inclusion criteria. Subcutaneous injection of insulin with hypertonic glucose significantly reduces time to healing by 6.33 days compared with conventional drainage, with less cost. There was no report concerning adverse effects. Subcutaneous injection of insulin with hypertonic glucose may improve the healing process in postoperative wounds with aseptic fat liquefaction. PMID- 22325040 TI - Semantics versus statistics in the retreat from locative overgeneralization errors. AB - The present study investigated how children learn that some verbs may appear in the figure-locative but not the ground-locative construction (e.g., Lisa poured water into the cup; *Lisa poured the cup with water), with some showing the opposite pattern (e.g., *Bart filled water into the cup; Bart filled the cup with water), and others appearing in both (Lisa sprayed water onto the flowers; Lisa sprayed the flowers with water). Grammatical acceptability judgments were obtained for the use of each of 142 locative verbs (60 for children) in each sentence type. Overall, and for each age group individually, the judgment data were best explained by a model that included ratings of the extent to which each verb exhibits both the broad- and narrow-range semantic properties of the figure- and ground-locative constructions (relating mainly to manner and end-state respectively; Pinker, 1989) and the statistical-learning measure of overall verb frequency (entrenchment; Braine & Brooks, 1995). A second statistical-learning measure, frequency in each of the two locative constructions (pre-emption; Goldberg, 1995), was found to have no additional dissociable effect. We conclude by drawing together various theoretical proposals to arrive at a possible account of how semantics and statistics interact in the retreat from overgeneralization. PMID- 22325041 TI - Genetic association analysis of LRCH-1 for knee osteoarthritis.